PMID- 12784146
TI  - Spectrum of breast cancer in Malaysian women: overview.
AB  - Breast cancer is the most common cancer among Malaysian women. Nonetheless, in
      Malaysia there is a marked geographical difference in the incidence of breast
      cancer with advanced stage of presentation. The breast clinic in Kuala Lumpur
      Hospital diagnosed approximately 150 to 200 new cases of breast cancer a year.
      This number, however, represents only 12.0% to 15.0% of all breast disease seen
      annually in Kuala Lumpur Hospital. Between 1998 and 2001, of a total of 774 cases
      of newly diagnosed breast cancer in Kuala Lumpur Hospital, only 5.0% (40/774)
      were impalpable breast cancers. The peak age group for the three major ethnic
      distributions (Malay, Chinese, and Indian) ranged from 40 to 49 years. The mean
      tumor size at presentation was 5.4 cm (range: 1-20 cm), and the advanced stage of
      breast cancer is observed to be highest among the Malay ethnic group. Although it
      appears that the incidence of breast cancer in Malaysia is lower than in the
      developed countries, the difference may be attributable to the difficulty in
      getting accurate statistics and to underreporting of cases. Nonetheless, from the
      available data, it is clear that breast cancer continues to be the most common
      cancer among Malaysian women. The strongly negative social-cultural perception of
      the disease, made worse by the geographical isolation of many rural areas,
      accounts for the delayed diagnosis and the often advanced stage of disease at
      presentation. A prospective population-based study is called for to verify the
      demographic patterns of breast cancer, particular in Malaysia and other
      developing countries. The findings of such a study may have implications for
      future breast screening programs and for facilitating the understanding of
      differing risks of breast cancer among women around the world.

PMID- 12784147
TI  - Medical and radiation oncology for breast cancer in developing countries with
      particular reference to locally advanced breast cancer.
AB  - The first part of this review outlines the extent of the problem of breast cancer
      in developing countries, with particular reference to the difficulties
      surrounding breast cancer treatment in these countries. The second part is
      devoted to discussion of chemotherapy, hormonal therapy, and radiotherapy
      treatments suitable for developing countries. The goals of the review are to show
      how treatment strategies can be adapted in poorer countries and how oncologists
      from the developed world can play a role in developing countries. This review
      should be relevant to the developing world in general, but as the author comes
      from South Africa, many of the examples are from that country which has features
      of the developed and developing world.

PMID- 12784148
TI  - Surgical competence.
AB  - Recent high-profile cases have heightened the need for a formal structure to
      monitor achievement and maintenance of surgical competence. Logbooks, morbidity
      and mortality meetings, videos and direct observation of operations using a
      checklist, motion analysis devices, and virtual reality simulators are effective
      tools for teaching and evaluating surgical skills. As the operating theater is
      also a place for training, there must be protocols and guidelines, including
      mandatory standards for supervision, to ensure that patient care is not
      compromised. Patients appreciate frank communication and honesty from surgeons
      regarding their expertise and level of competence. To ensure that surgical
      competence is maintained and keeps pace with technologic advances, professional
      registration bodies have been promoting programs for recertification. They
      evaluate performance in practice, professional standing, and commitment to
      ongoing education.

PMID- 12784150
TI  - Cardiac surgery in Eastern Europe: continuing challenge.
AB  - The post-Soviet calamities of East European cardiac surgery highlight the
      spectrum of marked differences in overall operative capacities among individual
      post-Communist countries. A comparison with the level of cardiac surgery in
      Western Europe reveals the importance of continuing relief, comprising both
      educational and material help. The East European Program of the European
      Association for Cardio-thoracic Surgery exemplifies current efforts to address
      these needs.

PMID- 12784149
TI  - Priority setting in surgery: improve the process and share the learning.
AB  - Surgeons and surgical programs encounter priority-setting challenges every day,
      such as in regard to purchasing new technologies or managing waiting lists for
      elective surgery. The purpose of this paper was to explore priority setting in
      surgery. Traditionally in surgery, priority-setting decisions for new
      technologies have been based on evidence of effectiveness and cost-effectiveness;
      and decisions about managing waiting lists for elective surgery have been based
      on urgency rating scores. The fairness of priority-setting processes in surgical
      programs should be enhanced to permit all relevant information and values to be
      considered. The quality of these decisions can be improved by using an approach
      that captures and shares lessons from each priority-setting experience. The
      approach we propose in this paper- describe, evaluate, and improve using a
      leading conceptual framework for priority setting, called "accountability for
      reasonableness"-can be used by any surgical program to improve its priority
      setting, share lessons with others, and develop an evidence base for how these
      important health policy decisions should be made.

PMID- 12784152
TI  - Radical surgery for mesothelioma: how can we obtain evidence?
AB  - Asbestos exposure in industry and construction sites in the 1960s and 1970s has
      left a legacy of mesothelioma, a diffuse pleural cancer, with a lag time of 40 to
      50 years and due to peak around 2015 to 2020. Some surgeons believe that by
      radical surgery they can prolong life and relieve symptoms, but the evidence
      comes from very carefully selected series. How do surgeons respond to demand for
      evidence of benefit? In this article we explore how evidence for major surgical
      operations has been gained and how mesothelioma fits into this history.

PMID- 12784163
TI  - QT dispersion in elderly athletes with left ventricular hypertrophy.
AB  - The purpose of this study was to examine the QT dispersion in elderly endurance
      athletes with left ventricular (LV) hypertrophy. Sixteen athletes (males, mean
      age 67.6 +/- 4.5 years) with mild to moderate LV hypertrophy, were compared with
      16 age-matched hypertensive patients with similar degree of LV hypertrophy and 16
      age-matched healthy sedentary controls. All the participants underwent
      echocardiogram and 12-lead electrocardiogram. QT dispersion was defined as the
      difference between maximum and minimum QT intervals in the different leads. QT
      dispersion was corrected (QTc) for heart rate according to Bazett's formula. The
      results showed in athletes and hypertensive patients comparable LV mass (258.2 +/
      14.2 vs. 262.4 +/- 16.8 g, ns), which was significantly higher than that of
      controls (p < 0.001). Trained subjects had QT dispersion (38.6 +/- 10.2 ms) and
      QTc dispersion (39.4 +/- 11.3 ms) significantly lower than hypertensive patients
      (QT dispersion: 68.4 +/- 11.4 ms; QTc dispersion: 72.2 +/- 8.4, p < 0.001) and
      comparable with controls (QT dispersion: 44.3 +/- 8.4 ms; QTc dispersion: 46.2 +/
      6.2 ms, ns). In conclusion, in elderly athletes training-induced myocardial
      hypertrophy was characterized by a QT dispersion significantly lower than
      hypertensive myocardial hypertrophy. This could provide a simple and inexpensive
      screening method for differentiating physiologic from pathologic myocardial
      hypertrophy in elderly subjects.

PMID- 12784164
TI  - 13C/31P NMR studies on the role of glucose transport/phosphorylation in human
      glycogen supercompensation.
AB  - This study measured muscle glycogen during a 7-day carbohydrate loading protocol.
      Twenty healthy subjects (12 male, 8 female) performed 1 hr treadmill/toe-raise
      exercise immediately before a 3-day low carbohydrate (LoCHO) diet (20 %
      carbohydrate, 60 % fat, 20 % protein). On day 3 they repeated the exercise and
      began a 4-day high carbohydrate (HiCHO) diet (90 % carbohydrate, 2 % fat, 8 %
      protein). The order of administration of the diet was reversed in a subpopulation
      (n = 3). Interleaved natural abundance 13C/ 31P NMR spectra were obtained before
      and immediately after exercise, and each day during the controlled diets in order
      to determine concentrations of glycogen (GLY), glucose-6-phosphate (G6P), and
      muscle pH. Following exercise, muscle GLY and pH were reduced (p < 0.001) while
      muscle G6P was elevated (p </= 0.01). During the 3-day LoCHO diet, fasting
      concentrations of G6P were not different from resting levels. During the first 3
      days of the HiCHO diet, resting G6P was elevated (p </= 0.05) compared to before
      the study. By the final day, muscle glycogen was 1.6-fold greater than before the
      protocol, while G6P had returned to baseline. Daily GLY and G6P were not affected
      by the order in which the diet was administered. We conclude that increased
      glucose transport/phosphorylation plays a role in muscle glycogen
      supercompensation.

PMID- 12784165
TI  - Effects of submaximal exercise on high-density lipoprotein-cholesterol
      subfractions.
AB  - Acute high-density lipoprotein-cholesterol (HDL) changes were determined in 18
      healthy college aged-men completing two-counterbalanced running trials at
      different exercise intensities: trial 1 at 70 % lactate threshold (LT) (372.5 +/-
      28.9 kcal); trial 2 at LT intensity (365.9 +/- 75.9 kcal). For each trial, blood
      samples were collected at pre-exercise (baseline), 15 min post-exercise (15 m PE)
      and 24 hours post-exercise (24 h). Serum samples were analyzed for HDL/HDL 2 /HDL
      3 subfraction, low density lipoprotein (LDL), very low density lipoprotein
      (VLDL), total cholesterol (TC), free cholesterol (FC), cholesterol ester, and
      triglycerides (TG). In addition, capillary blood samples were collected for
      analysis of blood lactate concentrations during incremental test to determine LT.
      All samples were corrected for plasma volume changes and compared to pre-exercise
      (baseline). In assessing the lipid and lipoprotein variables, the significant
      increase in HDL (p < 0.05) at the 24 h was due to the increase in both HDL 2 and
      HDL 3. The increase in 15 m PE TC at the LT intensity occurred while the
      decreases in 24 h TG and VLDL concentrations at the LT intensity occurred at
      different time periods, respectively. These decreases in the concentrations of TG
      and VLDL were significantly different, contributing to change in 24 h HDL
      concentration. No significant difference was determined in changes of HDL over
      time ratios of FC/CE and HDL 2 /HDL 3. Therefore, the significant increase in 24
      h HDL at LT intensity was potentially due to increases in both HDL 2 and HDL 3
      subfractions even though 24 h FC was increased significantly. Exercise at LT
      intensity might favourably alter the lipid profile as demonstrated in 24 h HDL
      concentration in combination with decreases in TG and VLDL at 24 h post-exercise.
      Consequently, the LT intensity might appear to be the threshold intensity of
      acute aerobic exercise (expending 350 kcal) necessary to promote a significant
      increase in HDL.

PMID- 12784166
TI  - Pharmacokinetic-pharmacodynamic modelling of recombinant human erythropoietin in
      athletes.
AB  - The aim of this study was to develop a pharmacokinetic model that takes into
      account the negative feedback loop of endogenous erythropoietin production
      observed after repeated recombinant human erythropoietin administration. A
      pharmacodynamic data analysis was performed using the changes in i) reticulocyte
      count, ii) serum levels of soluble transferrin receptors, and iii) soluble
      transferrin receptors/serum proteins ratio as an index of the therapeutic effect
      of the hormone. Nine athletes were included in the study; they received repeated
      subcutaneous administrations (50 IU x kg(-1) per day) of recombinant human
      erythropoietin. The mean half-life of the terminal part of the curve was 35.5 h,
      and the total clearance was 17 ml x h(-1) x kg(-1). The total clearance was about
      two times higher in athletes than in untrained subjects (5.5 - 7.5 ml x h(-1) x
      kg(-1)) and the half-life period of plasma erythropoietin after subcutaneous
      administration was five times longer compared to intravenous administration (4 to
      7 h). Thus, after subcutaneous administration, the terminal part of the curve
      should correspond to the absorption phase, instead of to the elimination phase
      (flip-flop phenomenon). The pharmacodynamic relationship based on a sigmoid Emax
      model can be reasonably used to relate the changes observed in the markers to
      recombinant human erythropoietin administration. Recombinant human erythropoietin
      induces a delayed increase in reticulocytosis and in soluble transferrin receptor
      levels. In comparison with baseline, the increase of these markers became
      significant from the third and the tenth day after the initial administration of
      the hormone, respectively. These results were in accordance with the
      equilibration delay computed from the pharmacokinetic-pharmacodynamic data
      modelling (half-life of 25.7 h and 10 days, respectively). The recombinant
      hormone was well tolerated during this study.

PMID- 12784167
TI  - Aerobic capacity and peripheral skeletal muscle function in coronary artery
      disease male patients.
AB  - The aim of this study was to determine if the diminished aerobic capacity of
      coronary artery disease male (CAD) patients is accompanied by an impaired
      skeletal muscle function compared to healthy control subjects. Thirteen CAD
      patients and 9 healthy subjects performed both a maximal laboratory exercise
      testing and an assessment of the peripheral skeletal muscle function on an
      isokinetic apparatus. The cardiorespiratory and mechanical parameters were
      measured at ventilatory threshold and at maximal effort during a maximal exercise
      testing. The peripheral skeletal muscle function of the quadriceps was assessed
      from the maximal voluntary isometric force (MVIF) and from the static endurance
      time (SET) at an intensity of 50 % of the MVIF. The CAD patients showed a
      diminished aerobic capacity compared to healthy control subjects at maximal
      effort (maximal VO(2) uptake: p < 0.0001, maximal ventilation: p < 0.01; maximal
      heart rate: p < 0.0001, maximal power: p < 0.001) but also at VT (VO(2) uptake
      VT: p < 0.0001, Power VT: p < 0.001). No difference was found on the MVIF (p <
      0.90) between the CAD patients and the control subjects whereas the SET was lower
      in the CAD patients (p < 0.01). The CAD patients had a lower aerobic capacity and
      an impaired skeletal muscle endurance compared to healthy subjects.

PMID- 12784168
TI  - Effects of high intensity resistance and low intensity endurance training on
      myosin heavy chain isoform expression in highly trained rowers.
AB  - An important mechanism of muscle adaptation to exercise is the alteration of
      myosin heavy chain (MHC) isoform expression. This study investigated the effect
      of a high intensity resistance training (HIRT) and a low intensity endurance
      rowing (LIER) on MHC isoform expression in highly trained human muscle. Six well
      trained male rowers underwent a training program consisting of a 3-week HIRT and
      a 3-week LIER, each followed by one-week of recovery. Muscle samples were taken
      from vastus lateralis before and at the end of each training and recovery phase.
      MHC isoform was analyzed by SDS-PAGE using silver stain and MHC isoform mRNA by
      RT-PCR. The maximum oxygen uptake and power output did not change after the
      training. MHC isoform composition did not change over HIRT or LIER, and there was
      a decrease in MHC I with concomitant increase in MHC IIa after recovery following
      HIRT. HIRT led to mRNA upregulation of MHC Ialpha, Ibeta and IIx (127 %, 148 %
      and 117 %, respectively, p < 0.05), but not MHC I protein (60 % vs 62 %, NS), and
      LIER led merely to MHC Ibeta mRNA upregulation (131 %, p < 0.05). Thus, different
      responses of MHC isoform expression to HIRT and LIER occurred in the highly
      trained muscle, and a "ceiling effect" in terms of MHC I expression could be
      observed. The upregulation of MHC Ialpha mRNA in human skeletal muscle documented
      in this study may encourage further observations in this field.

PMID- 12784170
TI  - Muscle elastic properties during wrist flexion and extension in healthy sedentary
      subjects and volley-ball players.
AB  - The aim of this study was to determine the effects of gender and chronic
      hyperactivity (training) on musculo-tendinous stiffness and joint flexibility and
      to examine in vivo whether those stiffness parameters were correlated. Thus,
      maximal isometric voluntary contraction, series elastic stiffness during wrist
      flexion and wrist extension, and wrist flexibility were investigated in healthy
      sedentary subjects and in women volley-ball players. Maximal isometric
      contraction and flexibility were measured classically with specific ergometers.
      Moreover, muscle stiffness measurements were performed thanks to the use of quick
      release movements of the wrist, which had previously been maintained in isometric
      contraction, allowing the calculation of a musculo-tendinous stiffness index.
      Despite significant differences in maximal voluntary contraction between wrist
      flexors and wrist extensors for each of the groups tested and between men and
      women, no significant gender, function or training effects were found upon
      musculo-tendinous stiffness indices. Flexibility assessments in both women groups
      demonstrated that active to passive ratios for wrist flexion remain unchanged
      whereas a significant training-induced increase for wrist extension was observed.
      Moreover, no significant relationship between women active joint flexibility and
      musculo-tendinous stiffness indices was found (r(2): 0.0004 - 0.0319, p > 0.05)
      whatever the muscle function tested. Collectively, the present results suggest
      that neural factors rather than morphological changes (i. e. muscle architecture
      and fiber composition) may explain predominantly the functional consequences
      observed in wrist extension associated with volley-ball training. Moreover, both
      musculo-tendinous stiffness and joint flexibility give different information
      about wrist functional status.

PMID- 12784169
TI  - Analysis of injuries in long-distance triathletes.
AB  - Triathlon is an individual sport consisting of three disciplines - swimming,
      cycling and running. Triathlon has changed from a novel appearance to a very
      popular Olympic sport within the last fifteen years. Nevertheless, there is not
      sufficient data about injuries in triathlon. The aim of this retrospective survey
      was to investigate the incidence of injuries according to class of injuries,
      anatomical sites and disciplines. Relations to age, sex, performance level,
      training habits and medical care were analysed. Questionnaires were sent to all
      German speaking participants of the Ironman Europe 2000. With a response rate of
      35 %, 656 questionnaires met the inclusion criteria. At least one injury was
      experienced by 74.8 % (95 %-CI: 71.3-78.1) of all respondents during their active
      time in triathlon. 51.1 % (95 %-CI: 47.2-55.0) suffered one or more
      contusion/skin-abrasions, 33.1 % (95 %-CI: 29.5-36.8) muscle-/tendon-injuries,
      29.0 % (95 %-CI: 25.5-32.6) ligament-/capsule-injuries and 11.9 % (95 %-CI: 9.5
      14.6) fractures. Most of the injuries happened during cycling (54.8 % [95 %-CI:
      51.9-57.8]) within training sessions. 18.7 % (95 %-CI: 16.4-21.2) of all injuries
      occurred while the athletes were competing. Considering the low number of
      competition hours per year, the incidence of injuries during competition was
      higher than during training session. Significant relations were found considering
      the age, performance level and weekly training hours of the triathletes. Older
      athletes sustained more fractures (p = 0.024), high performance athletes suffered
      more contusions/abrasions (p = 0.003) and muscle-tendon-injuries (p = 0.001) and
      athletes with a large number of weekly training hours suffered more muscle-tendon
      injuries (p = 0.014). To summarize, injuries in triathlon seem to be related to
      age, performance level and weekly training hours, but not to sex, presence of
      training coach and medical care.

PMID- 12784171
TI  - Reliability of rating scales of perceived exertion and heart rate during
      progressive and maximal constant load exercises till exhaustion in physical
      education students.
AB  - The purpose of this study was to assess the reliability of ratings of perceived
      exertion (RPE) and estimation of time limit (ETL) scales, and heart rate in
      physical education students during standardised and replicated progressive and
      constant load exercises till exhaustion realised on a track. Three groups of ten
      physical education students who present the same anthropometrical characteristics
      performed an incremental exercise to determine their maximal aerobic velocity
      (MAV) on an indoor track. Thereafter, group 1 performed an identical incremental
      exercise whereas groups 2 and 3 performed two identical exercises to exhaustion:
      a constant load exercise up to exhaustion at 90 and 100 % MAV, respectively, to
      determine the time to exhaustion at each intensity (tlim 90 and tlim 100). The
      results of this study were that MAV, tlim 90 and tlim 100 were not significantly
      different between the two trials. Moreover, the individual Pearson correlation
      coefficients between test and retests were very high (0.94 to 1). The slope and y
      intercept values of the relationships between test and retest perceived exertion
      ratings were not significantly different from the identity line. Moreover, test
      retest differences in HR values fell within the 95 % LoA analysis. Consequently,
      HR values, RPE and ETL scales are reliable during standardised and replicated
      progressive and constant load exercises till exhaustion performed on a track with
      physical education students.

PMID- 12784172
TI  - Time spent at VO2max: a methodological issue.
AB  - This study was designed to propose a standardised procedure to determine the time
      spent at VO2max (tVO2max) based on the VO2max of the day (i. e. the VO2max value
      measured the day of the test). Ten male subjects first performed a graded field
      test, followed by a continuous running exercise to exhaustion, at the velocity of
      the Universite de Montreal Track Test (V(UMTT)) plus 1 km x h(-1) (V(UMTT)(+1)).
      The second test consisted of an exhaustive run at 100 % of V(UMTT), followed by a
      V(UMTT)(+1) test. Different methods were used to compare time spent at VO2max,
      based on the VO2max of the graded field test, and time spent at VO2max, based on
      the VO2max of the day, during an exhaustive run at 100 % of V(UMTT). Results have
      shown that V(UMTT)(+1) tests were of sufficient intensity and duration to
      identify the VO2max of the day. Time spent at VO2max ranged from 25 +/- 53 s to
      139 +/- 76 s according to the method used. However, the tVO2max method based on
      the sum of each value higher than 95 % of VO2max of the day appeared more robust
      than methods based on the time to exhaustion minus time to reach VO2 reference
      value, or the method based on the sum of values higher than VO2max minus 2.1 ml x
      kg(-1) x min(-1).

PMID- 12784173
TI  - Comparison of MTI accelerometer cut-points for predicting time spent in physical
      activity.
AB  - The purpose of this study was to establish the accuracy of five published
      accelerometer regression equations that predict time spent in different intensity
      classifications during free-living activities. Ten participants completed
      physical tasks in a field setting for a near-continuous 5 - 6 h-period while
      oxygen uptake and accelerometer data were collected. The amount of time spent in
      resting/light, moderate and hard activity was computed from 3 and 6 MET cut
      points associated with five existing regression formulas relating accelerometer
      counts x min -1 to energy expenditure. The Freedson cut-points over-estimated
      resting/light activity by 34 min (13 %) and under-estimated moderate activity by
      38 min (60 %). The Hendelman cut-points for all activities underestimated
      resting/light activity by 77 min (29 %), and overestimated moderate activity by
      77 min (120 %). The Hendelman cut-points developed from walking activities over
      estimated resting/light activity by 37 min (14 %) and under-estimated moderate
      activity by 38 min (60 %). Estimates from the Swartz cut-points for estimating
      time spent in resting/light, moderate and hard intensity activity were not
      different from the criterion measure. The Nichols cut-points over-estimated
      resting/light activity by 31 min (12 %) and under-estimated moderate activity by
      35 min (55 %). Even though the Swartz method did not differ from measured time
      spent in moderate activity on a group basis, on an individual basis, large errors
      were seen. This was true for all regression formulas. These errors highlight some
      of the limitations to using hip-mounted accelerometers to reflect physical
      activity patterns. The finding that different accelerometer cut-points gave
      substantially different estimates of time spent data has important implications
      for researchers using accelerometers to predict time spent in different intensity
      categories.

PMID- 12784176
TI  - [Virtual bronchoscopy: supplement or in competition to conventional
      bronchoscopy].

PMID- 12784174
TI  - Effect of gender on mechanical power output during repeated bouts of maximal
      running in trained teenagers.
AB  - Seven high school boys (16.4 +/- 0.5 y, mean +/- SD) and 7 girls (16.4 +/- 0.5
      y), who specialized in track and field events, performed ten 5-s maximal sprint
      runs with an interval of 10s between each sprint on a non-motorized running
      ergometer. In each sprint, the mean mechanical power (MP) from the start until
      the belt velocity of the ergometer (i. e., running velocity) peaked was
      calculated. The boys showed significantly higher MP than the girls in all
      sprints. However, when MP was expressed as the ratio to the total volume of
      muscles located in the right lower limb (MP x MV(-1)), estimated using a
      bioelectrical impedance analysis, significant gender effect was limited to the
      values at the 1 st and 2 nd sprints. The decline of MP over the ten sprints,
      expressed as a relative value to that at the 1 st sprint, was greater in boys
      (46.2 +/- 7.6 %) than in girls (33.9 +/- 8.6 %), and significantly correlated
      with MP x MV(-1) at the 1st sprint (r = 0.568, p < 0.05). However, no significant
      difference between the boys and girls was found in the relative difference
      between MP values at the 3rd and 10th sprints, where the gender difference in MP
      x MV(-1) at every sprint was insignificant. The findings here indicate that, for
      trained teenage boys and girls, (1) significant gender difference in mechanical
      power developed during repeated bouts of maximal running exists only in the
      initial phase of the task, when the difference in the volume of the lower limb
      muscles is normalized, and (2) it may be a reason for a greater decline of
      mechanical power developed during the bout in boys compared to girls.

PMID- 12784177
TI  - [SARS--Severe Acute Respiratory syndrome].

PMID- 12784178
TI  - [Unusual gram positive rods, causing pneumonia].
AB  - In the last decade, a growing number of patients with pneumonia, caused by
      unusual gram positive rods have been observed. Mostly, the patients had been
      infected as a consequence of impaired immunity. In some cases, bioterrorist
      activities may also induce pneumonia by gram positive rods (B. anthracis). In
      order to bring these organisms to the attention of the medical community, we
      present three clinical cases and describe six species of gram positive rods,
      known to provoke this kind of pneumonias. Case 1 was a 84 years old patient with
      impaired lung function. He was suspicious of tuberculosis (Tbc). Nocardia spec.
      was isolated. Case 2 was an alcoholic of 46 years with pneumonia. Reactivation of
      Tbc was suspected. Actinomadura madurae has been isolated. Case 3 was a patient
      of 58 years with myelodysplastic syndrome (MDS) and pneumonia. N. asteroides was
      isolated. All patients shared impaired immunity (age, alcoholism, MDS) with
      impaired lung functions; Tbc had been suspected (Case 1 + 2). Infection by A.
      madurae was contained by Clindamycin. Therapy of Nocardia with Moxifloxacin (Case
      1) or Bactrim (Case 3) was only partly effective. In the appendix, six species of
      gram positive rods which are known to cause pneumonia, are summarized (Nocardia,
      Actinomyceta, Actinomadura, Rhodococcus, Corynebacterium and Bacillus).

PMID- 12784179
TI  - Necrotizing sarcoid granulomatosis--is it different from nodular sarcoidosis?
AB  - BACKGROUND: Necrotizing sarcoid granulomatosis (NSG) was initially defined as a
      granulomatosis with features in between sarcoidosis and Wegener's granulomatosis
      (WG), but without extrapulmonary involvement. Subsequent reports have shown that
      extrapulmonary involvement does exist, and some have suggested NSG as a variant
      of sarcoidosis. MATERIAL AND METHODS: We studied 10 cases from 3 institutions,
      and compared clinical and histologic features with those of nodular sarcoidosis
      and WG. We have analyzed the 10 cases for mycobacterial chaperonin and for the
      insertion sequence 6110 by PCR. RESULTS AND CONCLUSIONS: Nodular aggregates of
      granulomas in NSG were similar to those seen in nodular sarcoidosis. Granulocytic
      vasculitis, a hallmark of WG was not seen in any of the NSG cases. Granulomatous
      vasculitis was a common feature in cases of NSG, and did not differ from that
      seen in sarcoidosis. The only unique feature of NSG is infarct-like necrosis,
      induced by the vasculitis, which might also be interpreted as a function of the
      duration of the vasculitis, leading ultimately to vascular obstruction. NSG based
      on our morphologic findings is best classified as a variant of nodular
      sarcoidosis. In contrast to our findings in sarcoidosis mycobacterial DNA was not
      found in any of the 10 cases.

PMID- 12784180
TI  - [Virtual multislice-CT-bronchoscopy as a diagnostic tool in patients with
      endobronchial tumors: case report of a carcinoid tumor].
AB  - BACKGROUND: Bronchial carcinoids are rare neuroendocrine tumors of the lung.
      Diagnosis is established by computed tomography (CT) and bronchoscopy-guided
      biopsy. Imaging features of carcinoids are highly characteristic including
      contrast enhancement and central intraluminal growth. Multislice-CT generated
      three-dimensional virtual bronchoscopy enables non-invasive and detailed view of
      the tracheobronchial system. CASE REPORT: A 70-year-old male with known silicosis
      and chronic cough with hemoptysis showed hypertransparency of the left lung on
      conventional images. Axial CT scans revealed a solid tumor in the left lower
      lobe. Virtual CT-bronchoscopy based on surface rendering depicted an intraluminal
      mass occluding the bronchus of the anterobasal segment that was confirmed by
      conventional endoscopy. Conventional and virtual bronchoscopy showed almost
      identical imaging features. Histopathological evaluation of the bioptic specimen
      revealed a typical carcinoid tumor. The patient successfully underwent resection
      of the left lower lobe with mediastinal lymphadenectomy. CONCLUSIONS: Virtual
      Multislice-CT-bronchoscopy can add important information about an intraluminal
      tumor and its relation to surrounding structures. Further studies have to be
      undertaken to evaluate the potentials of this promising method as a tool to
      determine endoluminal growth in tumorous lung lesions.

PMID- 12784181
TI  - [Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)].
AB  - Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
      designates interstitial lung changes in smokers, characterized histologically by
      bronchiolocentric accumulation of pigmented alveolar macrophages and fibrotic or
      cellular inflammatory changes of pulmonary interstitium. The definition is nearly
      identical to that of condensate pneumopathy, smoker's pneumopathy or smoker's
      lung, defined by accumulation of pigmented alveolar macrophages with bland
      alveoloseptal or peribronchial fibrosis and cellular inflammation of the
      bronchial wall. In addition to respiratory bronchiolitis, which is found in
      nearly all smokers, RB-ILD comprises a broad spectrum of varying degrees of the
      interstitial reaction to the exogenous injury of inhalation smoking with gradual
      transition to desquamative interstitial pneumonia (DIP). In most cases RB-ILD
      manifestations are subclinical and detected coincidentally. Radiographic features
      are reticulonodular and ground glass opacities of the lung. The high resolution
      computed tomography reveals centrilobular nodules, ground glass opacities,
      thickening of bronchial walls, and in some cases a reticular pattern. Mild
      emphysema is frequent. Lung function analysis reveals only minor restrictive or
      obstructive defects in most cases, often combined with hyperinflation. CO
      diffusing capacity is slightly to moderately impaired. Pronounced interstitial
      lung diseases with serious restrictive defects and arterial hypoxemia have been
      reported infrequently. In differential diagnosis smoking related interstitial
      lung diseases (DIP, Langerhans cell histiocytosis, idiopathic pulmonary fibrosis)
      and other interstitial lung diseases have to be excluded. In most cases diagnosis
      can be achieved by bronchoalveolar lavage and transbronchial lung biopsy. In
      cases of pronounced interstitial lung disease or assumption of an additional
      interstitial lung disease besides RB-ILD a thoracoscopic or open lung biopsy can
      be necessary. RB-ILD has a favourable prognosis. After smoking cessation lung
      changes are reversible. Corticosteroid therapy is not necessary. A fatal outcome
      of RB-ILD has not been reported. Follow-up examinations are advisable in order to
      preclude other interstitial lung diseases. RB-ILD seems to be more frequent than
      it is assumed at present. The clinical picture is masked in most cases by the
      concomitant smoking induced chronic bronchitis. Thus only pronounced cases with
      structural changes and resulting differential diagnostic problems are diagnosed.

PMID- 12784182
TI  - Fighting against the "Hypertriglyceridaemic Waist": a new international institute
      for the metabolic syndrome.

PMID- 12784184
TI  - Commentary for debate--the ALLHAT-study.

PMID- 12784183
TI  - Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin
      resistance and type 2 diabetes.
AB  - Most obese individuals have elevated plasma levels of free fatty acids (FFA)
      which are known to cause peripheral (muscle) insulin resistance. They do this by
      inhibiting insulin-stimulated glucose uptake and glycogen synthesis. The
      mechanism involves intramyocellular accumulation of diacylglycerol and activation
      of protein kinase C. FFAs also cause hepatic insulin resistance. They do this by
      inhibiting insulin-mediated suppression of glycogenolysis. On the other hand,
      FFAs support between 30 and 50 % of basal insulin secretion and potentiate
      glucose-stimulated insulin secretion. The insulin stimulatory action of FFAs is
      responsible for the fact that the vast majority ( approximately 80 %) of obese
      insulin resistant people do not develop type 2 diabetes. They are able to
      compensate for their FFA mediated insulin resistance with increased FFA mediated
      insulin secretion. Individuals who are unable to do this (probably for genetic
      reasons) eventually develop type 2 diabetes. FFAs have recently been shown to
      activate the IkappaB/NFkappaB pathway which is involved in many inflammatory
      processes. Thus, elevated plasma levels of FFAs are not only a major cause of
      insulin resistance in skeletal muscle and liver but may, in addition, play a role
      in the pathogenesis of coronary artery disease.

PMID- 12784185
TI  - Antibodies to heat-shock protein 65 and neopterin levels in patients with type 1
      diabetes mellitus.
AB  - Antibodies to heat shock protein (hsp) are strongly associated with
      atherosclerotic cardiovascular disease in the non-diabetic population as well as
      in patients with type 2 diabetes mellitus. In type 1 diabetes increased antibody
      titers to hsp were found to be a symptom of the autoimmune disease leading to
      beta-cell damage. We asked whether hsp antibody titers are related to metabolic
      control and late complications in type 1 diabetic patients. Serum neopterin, also
      an indicator of chronic inflammation, was also evaluated. The hsp65 antibody
      titer was determined in 138 patients with type 1 diabetes, 47 women and 91 men,
      aged 35.5 +/- 12 years with a mean diabetes duration of 16.6 +/- 10.5 years. A
      history of diabetic late complications and cardiovascular disease was taken. A
      fundoscopy and a neurological examination were performed, nephropathy was
      assessed by measurement of the urinary albumin excretion rate. For the
      measurement of the hsp antibody titer an enzyme-linked immunosorbent assay
      (ELISA) was applied, for neopterin a radio-immuno assay (RIA) was used. The hsp65
      antibody titer was found to be positively related to the patients' age (r =
      0.237; p < 0.035). Patients with retinopathy revealed significantly higher hsp65
      antibody titers (307.2 +/- 38.6) than those without retinopathy (150.0 +/- 18.5;p
      < 0.003). No correlation was found between hsp antibody titer and metabolic
      control. Serum neopterin levels revealed a trend towards a positive relationship
      with diabetes duration (r = 0.205; p < 0.0539) and a significant correlation with
      serum cholesterol levels (r = 0.436; p < 0.001), but not with HbA1 c values. Our
      data add further information to the role of inflammatory markers in the
      development of diabetic microangiopathy.

PMID- 12784186
TI  - The association between end-stage diabetic nephropathy and
      methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2
      diabetes mellitus.
AB  - The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene
      polymorphism is associated with elevated homocysteine levels and presumably with
      increased atherosclerotic risk. We evaluated the interaction between this gene
      polymorphism and end-stage diabetic nephropathy on the observed prevalence of
      macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate
      reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80
      with and 94 without renal failure due to diabetic nephropathy. In the patients
      with renal failure, the T/T genotype and T allele were significantly associated
      with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P =
      0.00014), whereas the associations were not significant in the patients without
      renal failure. In the multiple logistic regression analysis, age (10 years OR
      4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P =
      0.0013) were significantly associated with macroangiopathy in the patients with
      renal failure. In conclusion, this study demonstrated that the 677 T/T genotype
      and T allele of MTHFR were significantly associated with macroangiopathy in type
      2 diabetic patients with renal failure. The MTHFR 677 T allele, together with
      renal dysfunction due to diabetic nephropathy, could be a strong risk factor for
      atherosclerotic disease.

PMID- 12784187
TI  - Insulin-like effect of low-dose leptin on glucose transport in Langendorff rat
      hearts.
AB  - BACKGROUND: In a murine myotube cell line (C 2 C 12 myotubes), leptin at low
      physiological concentrations (1 ng/ml) has been shown to stimulate glucose
      transport and glycogen synthesis. The aim of the present study was to test
      whether an analogous leptin effect on glucose transport is detectable in the
      heart. METHODS AND RESULTS: We used the isolated Langendorff rat heart
      preparation with hemodynamic function control. Using polymerase chain reaction
      (RT-PCR), a 346- and 375-base fragment indicative for the short and long leptin
      receptor isoform was detected in the rat heart. Glucose transport rates were
      calculated using equimolar double tracer perfusion with the non-metabolizable
      glucose analog 3-O-methylglucose (3-O-MG) and the non-transportable tracer
      mannitol and two-compartimental modeling. 3-O-MG uptake at a perfusate glucose
      concentration of 11 mM was measured over 15 minutes in control hearts, hearts
      perfused with insulin (10 mU/ml), leptin (1 ng/ml) or insulin (10 mU/ml) plus
      leptin (1 ng/ml; n = 8 in each group). The basal 3-O-MG transport rate of 0,7351
      +/- 0,051 micro mol/min/g wet weight was increased 4.18 fold with insulin, 2.69
      fold with leptin, and 4.2 fold with leptin plus insulin. Simultaneous monitoring
      of hemodynamic function revealed a minor and transient effect of leptin on left
      ventricular pressure, which was strongly augmented in coperfusion with insulin.
      CONCLUSIONS: The data suggest that leptin at low physiological concentrations is
      able to exert a partial insulin like effect on glucose uptake. We speculate that
      the effect might be mediated by both leptin receptor isoforms. This leptin effect
      is additive to the effect of insulin and might therefore contribute to the
      insulin independent basal glucose supply of the heart. It can not be completely
      excluded that the observed leptin effect on glucose transport is secondary to
      altered myocardial function.

PMID- 12784188
TI  - Targeted destruction of normal and cancer cells through
      lutropin/choriogonadotropin receptors using Hecate-betaCG conjugate.
AB  - A recent approach to cancer treatment is destruction of malignant and non
      malignant tumors by hormonally targeted lytic peptides. The presence of
      lutropin/choriogonadotropin (LH/CG) receptors has been confirmed in several
      cancer cells (e.g. breast, ovarian, and prostate). In a series of experiments
      conducted in vitro, we have used a conjugate of the 23-amino acid lytic peptide
      Hecate and a 15-amino acid segment of beta-chain of CG. To test the hypothesis
      that Hecate-betaCG selectively destroys porcine granulosa and luteal cells, and
      Leydig cancer cell line (BLT-1) possessing LH/CG receptors, the conjugate was
      added to culture media at different concentrations of 0.5 to 10 micro M. Spleen
      cells and late passage of granulosa cancer cell line (KK-1) not-possessing LH/CG
      receptors were used as controls. The toxicity of Hecate-betaCG conjugate was
      concentration-dependent in all cell types but different among various cells. The
      toxicity of the conjugate to treated cells was closely correlated with the number
      of LH/CG receptors per cell. At low concentration (1 micro M), Hecate-betaCG was
      more cytotoxic to cells bearing LH/CG receptors than to controls (p < 0.01). In
      contrast to cells possessing LH/CG receptors, cancer cell line KK-1 and spleen
      cells were sensitive only at concentration of 5 micro M (p < 0.001). We conclude
      that Hecate-betaCG selectively kills cells expressing LH/CG receptors; its
      toxicity is dependent on the number of binding sites for LH/CG.

PMID- 12784189
TI  - Expression patterns of CRH, CRH receptors, and CRH binding protein in human
      gestational tissue at term.
AB  - Recent research suggests a significant role for placental corticotropin-releasing
      hormone (CRH) in controlling human parturition. This paper describes the
      expression of CRH, CRH receptors 1 and 2, and CRH binding protein (CRH-BP) in
      gestational tissue in late pregnancy. Placenta, myometrium, decidua, and fetal
      membranes were collected after uncomplicated pregnancies at term caesarian
      section before the onset of labour. The localisation and mRNA expression of CRH,
      CRH receptors, and CRH-BP were studied by immunohistochemistry and reverse
      transcription (RT)-PCR. CRH receptors were detected in placenta, myometrium,
      decidua, and fetal membranes. We demonstrated for the first time the presence of
      CRH receptors on resident macrophages and on endothelial cells. CRH receptor 1
      mRNA was detected in all tissues investigated by RT-PCR, whereas CRH receptor 2
      mRNA was restricted to myometrium and decidua. CRH mRNA was widely expressed in
      all tissue under study. Novel findings are also presented on the expression of
      CRH-BP in the myometrium. This widespread expression of the CRH system in
      gestational tissue suggests a paracrine role for CRH in the birth process (e.g.
      effects on macrophages and endothelial cells).

PMID- 12784190
TI  - Endocrine findings in patients with optico-hypothalamic gliomas.
AB  - OBJECTIVES: Optico-hypothalamic gliomas (OHG) are an important differential
      diagnosis in suprasellar tumors. Visual impairment and hydrocephalus are the most
      frequent findings at presentation. However, only limited data are available about
      endocrine disturbances in these lesions. PATIENTS AND METHODS: 38 consecutive
      patients (19 children) were studied retrospectively. Clinical assessment and
      endocrinological evaluation of pituitary and hypothalamic functions (combined
      pituitary stimulation test, ITT, CRH-GRH test) were performed before and after (1
      week and 3 months) the neurosurgical procedure. RESULTS: Only three patients
      showed clinical features of endocrine deficiency initially. 16 children and 15
      adults out of the 38 patients (31/38, 81.6 %) showed no abnormality in their
      hormone values when assessed with the combined pituitary stimulation test alone
      or using more sophisticated investigations such as ITT and CRH-GRH test (72.2 %).
      Patients with hypothalamic disturbances (8 out of 38, 21 %) had endocrine
      abnormalities more frequently than those without (57.1 % vs. 9 %, p < 0.05), as
      assessed by ITT and CRH-GRH-test. CONCLUSIONS: In contrast to other suprasellar
      tumors, endocrine deficiencies are surprisingly rare in optico-hypothalamic
      gliomas despite their large size, especially in the absence of hypothalamic
      disorders. This may be used as a criterion in the differential diagnosis of these
      lesions, in addition to the radiological findings.

PMID- 12784191
TI  - Volumetric bone mineral density in patients with childhood craniopharyngioma.
AB  - As the overall survival rate is high in patients with craniopharyngioma, the
      prognosis in survivors depends mainly on late effects. Late effects such as
      hypogonadism, growth hormone deficiency, glucocorticoid overreplacement and
      obesity have a strong impact on volumetric bone mineral density (vBMD). We
      analyzed vBMD and possible risk factors for reduced vBMD in 61 patients with
      childhood craniopharyngioma (29 f; 32 m) and in 14 weight, age, and sex-matched
      controls. VBMD was quantified by peripheral quantitative computed tomography
      (pQCT). Endocrine status, hormonal substitution therapy and calcium phosphate
      metabolism were evaluated. VBMD was in the lower normal range in 61
      craniopharyngioma patients (total radial z-scores: median - 1.5; range - 3.1 to
      1.4; trabecular z-scores: median - 0.4; - 2.4 to 2.3). 23 severely obese patients
      (body mass index [BMI] > 4 SD) had a higher total radial (p < 0.05) and
      trabecular (p < 0.05) vBMD when compared with 38 non-severely obese patients and
      7 weight-matched controls. Although there was no gender difference in terms of
      obesity, endocrine substitution therapy or calcium phosphate metabolism, male
      patients had lower total radial (p < 0.01) and trabecular (p < 0.05) vBMD. Only
      in male patients' vBMD z-scores showed a positive correlation with BMI standard
      deviation score (SDS) (total radial z-score: Spearman r = 0.38, p = 0.03;
      trabecular z-score: Spearman r = 0.35, p = 0.04). We conclude that obesity has a
      major impact on vBMD in patients with craniopharyngioma. Lean male patients are
      at special risk for a lower vBMD, whereas female gender and severe obesity seem
      to have a protective effect regarding vBMD.

PMID- 12784192
TI  - A novel AIRE mutation in an APECED patient with candidiasis, adrenal failure,
      hepatitis, diabetes mellitus and osteosclerosis.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare
      autosomal recessive disorder, which is characterized by an immune-mediated
      destruction of endocrine tissues, chronic candidiasis and ectodermal disorders.
      In contrast to many other autoimmune diseases, APECED is associated with
      mutations of a single gene, designated autoimmune regulator (AIRE). We describe
      an APECED patient with severe deformities of the tibia with radiological signs of
      metaphyseal dysplasia in addition to candidiasis, hepatitis, diabetes mellitus
      and adrenal failure. In this patient, we identified a novel AIRE mutation in
      association with the C322fsX372 mutation in exon 8, which is frequently detected
      in Caucasian patients. The frame shift mutation G263fsX377 in exon 6 results in a
      protein lacking both PHD zinc-finger domains similar to the R257 X mutation. This
      novel mutation was not found in 50 German controls.

PMID- 12784193
TI  - Pitfall in diagnosing growth hormone deficiency in a hypochondroplastic patient
      with a delayed puberty.
AB  - Hypochondroplasia is a clinically and genetically heterogeneous skeletal
      dysplasia with less obvious disproportion in childhood and a reduced pubertal
      growth spurt. We report on a young hypochondroplastic man who had been
      misdiagnosed and treated as being growth hormone (GH) deficient in the early
      phase of puberty. The delay of his puberty which is unusual in hypochondroplasia
      might have confused the results of provocative GH testing. At the age of 17 years
      measurement of body proportions revealed an increased upper to lower body segment
      ratio. Skeletal radiographs showed a lack of increase in the interpedicular
      distance from the first to the fifth lumbar vertebra, anteroposterior shortening
      of the lumbar pedicles, short femoral necks, a fibula longer than the tibia, and
      short tubular bones. As the clinical and radiographic features suggested the
      diagnosis of a skeletal dysplasia, a DNA sequence analysis of the fibroblast
      growth factor receptor 3 gene on chromosome 4 p16.3 was performed, which
      identified the missense mutation C1620 G in the tyrosine kinase domain resulting
      in an Asn540Lys substitution. Hypochondroplastic children with this common
      mutation (N540K) were previously found to respond to GH treatment with an
      increase in sitting height compared to leg length, which accentuated the existing
      disproportion. We want to emphasise that in children with normal serum IGF-I and
      IGFBP-3 levels accurate measurements of body proportions and skeletal radiographs
      in disproportionate cases are more important than reiterative GH stimulation
      tests, which prepubertally and in the early phase of puberty often show subnormal
      responses.

PMID- 12784194
TI  - Severe carpometacarpal osteoarthritis in older Arabian horses.
AB  - OBJECTIVE: To report a severe form of carpometacarpal osteoarthritis (CMC-OA)
      affecting primarily older Arabian horses. STUDY DESIGN: Retrospective study.
      ANIMALS: Thirty-one horses with CMC-OA. METHODS: Carpal radiographs (405 sets)
      from 3 hospitals were evaluated to identify horses with marked osteoproliferative
      reaction across the medial aspect of the CMC joint. Owners were contacted to
      obtain detailed histories and status updates. Necropsy specimens of the CMC joint
      were evaluated at 2 hospitals to determine the prevalence of 2 variations in the
      articulation between the proximal second and third metacarpal bones. RESULTS:
      Thirty-one horses were identified as having marked osteoproliferative reaction at
      the CMC joint. Twenty-three (74%) were Arabian horses. Of the Arabian horses, the
      average age at admission was 14.4 years. Eight (34.8%) Arabian horses had a known
      history of trauma. Most were no longer rideable at presentation. Ten of the
      horses were subsequently euthanatized because of lameness. The dorsal and palmar
      articulations between the second and third metacarpal bones were examined in 177
      horses. The palmar articulation was absent in 48% of Arabian horses and 12.5% of
      non-Arabian horses at 1 center, including 4 horses with CMC-OA. At the second
      center, the palmar articulation was present in 8 of 8 Arabian horses but was
      absent in 22 of 92 (24%) non-Arabian horses. CONCLUSIONS: An increased frequency
      of this crippling form of OA was observed in Arabian horses. It may reflect an
      increased prevalence, in some geographical regions, of an absent palmar
      articulation between the second and third metacarpal bones. CLINICAL RELEVANCE:
      Carpal trauma in some Arabian horses may result in unexpectedly severe
      carpometacarpal osteoarthritis.

PMID- 12784195
TI  - Effect of dorsal hip loading, sedation, and general anesthesia on the
      dorsolateral subluxation score in dogs.
AB  - OBJECTIVE: To determine whether dorsal loading of the pelvis and type of chemical
      restraint affected the dorsolateral subluxation (DLS) score of dog hips. STYDY
      DESIGN: In vivo testing of diagnostic method. ANIMALS: Labrador retrievers,
      Greyhounds, and crosses between both breeds (n = 119 dogs). METHODS: Dorsal load
      was applied to the hips through a strap that was placed over the hips, and the
      peak vertical and steady-state vertical, ground-reaction forces exerted on the
      stifles were measured in the DLS position. The DLS score was measured with their
      hips under dorsal load and compared with the DLS score without load. For 24 dogs,
      the DLS score was measured both under chemical restraint (medetomidine) and under
      general anesthesia. Wilcoxon-signed rank test and paired t test was used to
      compare effects of dorsal load and restraint method on the left and right DLS hip
      score, and P <.05 was considered significant. RESULTS: Both stifles together
      accepted median 15% body weight in the vertical plane in the unloaded steady
      state. Loading the hips increased the steady-state, vertical ground-reaction
      force to 34% body weight. At 8 months of age, loading significantly decreased the
      DLS score from 65% +/- 11% (mean +/- SD) to 60% +/- 12% for left hips and 66% +/-
      11% to 63% +/- 13% for right hips. The left hip DLS score was affected by load
      more consistently than the right hip. In general, loading the hips decreased the
      DLS score in all breeds by 4% to 6% except for the greyhounds, in which the DLS
      score was unchanged by dorsal loading. When grouped by their DLS scores, load
      significantly decreased DLS scores in dogs with unloaded scores greater than 55%
      (nondysplastic), whereas DLS scores of dogs with unloaded scores between 55% and
      45% (dysplastic) and less than 45% did not change significantly with load.
      Unloaded scores did not change significantly when compared under sedation versus
      general anesthesia. However, load significantly decreased the DLS score under
      general anesthesia for the left hip but not for the right hip. CONCLUSIONS: Less
      than half of the vertical ground-reaction force normally exerted by the hindlegs
      of a standing dog was sufficient to induce hip subluxation in the DLS position.
      Although dorsal loading approximately doubled the steady-state, vertical ground
      reaction force, the decrease in the DLS score under load was never greater than
      6%. Furthermore, the DLS scores of dogs most likely to be dysplastic (based on
      DLS scores <45%) were not affected by load, whereas load slightly decreased DLS
      cores of dogs with DLS scores greater than 55%. CLINICAL RELEVANCE: External
      influences can change the DLS score significantly, but the magnitude of change is
      unlikely to be of clinical importance, making the method useful as a field
      screening test for both dysplastic and nondysplastic hips in young dogs.

PMID- 12784196
TI  - Hand-assisted laparoscopic left nephrectomy in standing horses.
AB  - OBJECTIVE: To describe a hand-assisted, laparoscopic technique to remove the left
      kidney in standing horses. STUDY DESIGN: Prospective evaluation. ANIMALS: Eight
      horses. METHODS: Food was withheld for a minimum of 12 hours. Horses were sedated
      with detomidine hydrochloride (0.01-0.02 mg/kg, intravenously) and restrained in
      standing stocks. The left paralumbar fossa was prepared for surgery, and the
      surgical site was infiltrated with 2% mepivacaine. Hand-assisted, laparoscopic
      removal of the left kidney was performed through an incision in the center of the
      paralumbar fossa; the surgeon's hand was used to isolate the left kidney and
      associated vasculature. The renal artery and vein were isolated and individually
      ligated. After vessel transection distal to the ligatures, the left kidney was
      exteriorized, the ureter ligated and transected, and the incision closed.
      RESULTS: Laparoscopic removal of the left kidney was successfully performed in
      all horses. Retroperitoneal infiltration of local anesthesia provided adequate
      anesthesia. Intraoperative hemorrhage occurred in 3 horses. Surgical duration
      (initial skin incision to transection of the left kidney) ranged from 20 to 90
      minutes. In 2 horses, no signs of pain were noted for 48 hours postoperatively.
      CONCLUSION: Hand-assisted laparoscopic surgery can be used for removal of the
      left kidney in horses. Clinical Relevance-Hand-assisted laparoscopic nephrectomy
      can be safely performed in standing horses; however, care should be taken to
      identify accessory branches of the renal artery to limit potential complications
      with hemorrhage.

PMID- 12784197
TI  - Microemulsified cyclosporine-based immunosuppression for the prevention of acute
      renal allograft rejection in unrelated dogs: preliminary experimental study.
AB  - OBJECTIVES: To determine whether the microemulsified formulation of cyclosporine
      (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo
      Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in
      preventing acute renal allograft rejection in unrelated mongrel dogs. To document
      any toxic effects associated with this drug combination. STUDY DESIGN:
      rospective, pilot study. ANIMALS: Four healthy, adult, mongrel, canine renal
      allograft recipients. METHODS: Heterotopic renal transplantation, with bilateral
      nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated
      dogs that were to be euthanatized for reasons unrelated to this study. The dogs
      were treated for 100 days or until signs of illness or allograft rejection
      required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5
      mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the
      prevention of acute rejection. Body weight, serum biochemistry profiles, complete
      blood counts, and trough whole-blood cyclosporine concentrations were measured
      throughout the study. Cyclosporine dose was adjusted to maintain a trough
      concentration of 400-500 ng/mL. Azathioprine dose was decreased if evidence of
      hepatotoxicity developed or if the total blood white cell count was <4,000
      cells/micro L. The prednisolone was tapered by 0.25 mg/kg increments every 3
      weeks and discontinued 14 days before the end of the study in the surviving dogs.
      Complications were recorded. A complete necropsy and histopathologic examination
      were performed in each recipient. RESULTS: Two of the 4 dogs survived the 100-day
      period. One dog was euthanatized at 8 days because of an intestinal
      intussusception. One dog was euthanatized at 64 days because of a severe upper
      respiratory infection. At the time of death, these 2 dogs had plasma creatinine
      concentrations of 1.5 and 2.6 mg/dL, respectively, with no histopathologic
      evidence of allograft rejection. All dogs had transient weight loss (range, 4.6%
      17.7% of preoperative body weight) between days 7 and 14. Two dogs had evidence
      of hepatotoxicity. The 2 dogs surviving to 100 days had normal serum creatinine
      concentrations and no clinical signs of rejection. One of these dogs had evidence
      of a grade IIa acute/active rejection based on the modified BANFF 97
      histopathologic classification. The second dog had no evidence of rejection or
      inflammation within the allograft. CONCLUSIONS: This preliminary experimental
      study shows that immunosuppression using MCsA, combined with azathioprine and
      prednisolone, may be effective in preventing acute renal allograft rejection in
      unrelated mongrel dogs for 100 days. Complications included ileocolic
      intussusception, upper respiratory infection, weight loss, and transient
      hepatotoxicity. CLINICAL RELEVANCE: Immunosuppression using MCsA, azathioprine,
      and prednisolone may be effective in preventing acute renal allograft rejection
      in unrelated, mongrel dogs. This triple drug protocol is cost-effective and was
      easy to administer. Further investigation is warranted to minimize toxic effects
      and to determine the efficacy of prophylactic renal biopsies to detect and treat
      subclinical acute/active rejection.

PMID- 12784198
TI  - Cylindrical press-fit osteochondral allografts for resurfacing the equine
      metatarsophalangeal joint.
AB  - OBJECTIVE: To investigate the feasibility of resurfacing the equine fetlock joint
      using cylindrical, orthotopic, press-fit, osteochondral allografts. STUDY DESIGN:
      Experimental study. ANIMALS: Ten mature, mixed-breed horses. METHODS:
      Cylindrical, osteochondral grafts (6.5-mm diameter) were harvested aseptically
      from cadaveric equine metatarsophalangeal joints. Allografts were transplanted
      into 6 horses; 4 horses were sham operated. The surgical approach involved
      creation of a bone block at the origin of the medial collateral ligament and
      luxation of the metatarsophalangeal joint. Grafts were placed into the medial and
      lateral metatarsal condyles. Radiographs were taken at 8 and 25 weeks, and
      lameness was evaluated at 25 weeks. Horses were killed at 25 weeks. Analyses
      included gross evaluation, microradiography, paravital staining, light
      microscopy, and cartilage biochemistry. RESULTS: No complications occurred that
      could be attributed to the surgical procedure. Graft congruency with the
      surrounding articular cartilage was fair to excellent. Two horses were sound at
      25 weeks. Most grafts had more than 90% articular cartilage coverage, and
      histologic and microradiographic analysis revealed good graft incorporation and
      articular cartilage survival. Sulphated glycosaminoglycan concentration was
      decreased in grafted tissue. CONCLUSIONS: We attribute the viability of
      osteochondral allografts in the equine fetlock to adequate congruency, stable
      graft fixation, and the use of orthotopic tissue. Host response to the allograft
      bone tissue did not affect cartilage viability. CLINICAL RELEVANCE: Before
      clinical use, improvements to instrumentation are required that would decrease
      damage to grafts and minimize technique-associated incongruencies of the
      articular surface at the time of grafting. Larger grafts would also likely be
      required to resurface a greater surface area.

PMID- 12784199
TI  - Comparison of the incidence of residual shunting between two surgical techniques
      used for ligation of patent ductus arteriosus in the dog.
AB  - OBJECTIVE: To compare the incidence of residual patent ductus arteriosus (PDA)
      flow after ligation using 2 different dissection techniques: a standard
      dissection and a method described by Jackson and Henderson. STUDY DESIGN: A
      randomized, prospective study. ANIMALS: Thirty-five dogs admitted for surgical
      correction of a left to right shunting PDA. METHODS: Dogs were randomly assigned:
      19 to a standard dissection technique (group S) and 16 to the Jackson and
      Henderson dissection group (group JH). RESULTS: Gender ratio, age at surgery, and
      diameter of the ductus were not statistically different between groups. Breed
      distribution was also similar. Because 1 dog had fatal intraoperative hemorrhage,
      only 34 dogs were available for residual flow comparisons. Twenty-one percent of
      group S dogs had residual flow compared with 53% in group JH. Whereas no
      intraoperative complications occurred in group S, 3 were encountered in group JH.
      CONCLUSIONS: The incidence of residual flow was higher when the Jackson and
      Henderson dissection was used for PDA ligation compared with a standard method of
      dissection. This was probably because of entrapment of loose connective tissue
      within the medial aspect of the ligature, impeding complete closure of the
      ductus. CLINICAL RELEVANCE: Ideal PDA closure should result in no residual ductal
      flow to prevent possible adverse long-term sequelae, such as recanalization and
      infective endocarditis.

PMID- 12784200
TI  - Concurrent use of a medial saphenous fasciocutaneous free tissue flap and
      external skeletal fixation for treatment of a distal antebrachial injury in a
      dog.
AB  - OBJECTIVE: To report the surgical management of a traumatic distal antebrachial
      wound using a medial saphenous fasciocutaneous free tissue flap and a type I
      external skeletal fixator (ESF). STUDY DESIGN: Case report. ANIMALS: A 7-year-old
      spayed, female Labrador retriever. RESULT: Wound coverage and pancarpal
      arthrodesis were accomplished during a single anesthetic episode using a medial
      saphenous fasciocutaneous free tissue flap and type I ESF. A second surgical
      procedure was performed to expedite healing of part of the original wound that
      was initially left to heal by second intention. CONCLUSIONS: Free tissue transfer
      can be used in combination with an ESF for repair of distal antebrachial wounds,
      allowing orthopedic repair and soft tissue coverage in a single anesthetic
      episode. CLINICAL RELEVANCE: Concurrent use of free tissue transfer and carpal
      arthrodesis with an ESF could be used for repair of complex antebrachial wounds
      without need for multiple procedures, extended hospitalization, and increased
      cost.

PMID- 12784201
TI  - Evaluation of the harmonic scalpel for laparoscopic bilateral ovariectomy in
      standing horses.
AB  - OBJECTIVE: To evaluate use of the Harmonic Scalpel (Ethicon Endo-Surgery Inc.,
      Cincinnati, OH) for performing laparoscopic bilateral ovariectomy in standing
      horses. STUDY DESIGN: Experimental study. ANIMALS: Eight mares aged 2-20 years
      and weighing 410-540 kg. METHODS: Standing laparoscopic bilateral ovariectomy was
      performed in 8 mares with normal reproductive tract anatomy. The Harmonic Scalpel
      (an ultrasonically activated instrument) was used to simultaneously transect and
      obtain hemostasis of the ovarian pedicle. Necropsy was performed on 4 mares 3
      days after surgery and 4 mares 30 days after surgery. Gross and histopathologic
      evaluation of the ovarian pedicles was performed to characterize tissue reaction.
      RESULTS: Complete hemostasis of the ovarian pedicles was obtained in all mares.
      Median transection time for the ovarian pedicle was 28 minutes. Postoperative
      complications included transient fever, moderate subcutaneous emphysema, and
      incisional seroma formation. On necropsy examination, there were no signs of
      generalized peritonitis, postoperative hemorrhage, or adhesion formation. Mild to
      moderate acute inflammation and scar formation with moderate chronic inflammation
      at the ovarian pedicle was found at 3 and 30 days. Median depth of coagulation
      necrosis at 3 days was 2.87 mm. CONCLUSIONS: The Harmonic Scalpel appears to
      provide reliable hemostasis of the ovarian pedicle during elective laparoscopic
      ovariectomy in horses. Clinical Relevance-The Harmonic Scalpel represents a safe
      alternative to other methods of hemostasis during elective laparoscopic
      ovariectomy in horses.

PMID- 12784202
TI  - Elution of metronidazole and gentamicin from polymethylmethacrylate beads.
AB  - OBJECTIVE: To characterize the elution and bioactivity of metronidazole and
      gentamicin sulfate polymerized, individually and in combination, with
      polymethylmethacrylate (PMMA). STUDY DESIGN: In vitro experimental study.
      METHODS: PMMA beads containing metronidazole (3 concentrations), gentamicin
      sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of
      phosphate-buffered saline in triplicate. Eluent was replaced at specified time
      intervals for 1 or 21 days, and antibiotic concentrations were measured by high
      performance liquid chromatography. Changes in antibiotic bioactivity attributable
      to polymerization or copolymerization of the antibiotics with PMMA, ethylene
      oxide sterilization, and storage of AIPMMA beads containing metronidazole were
      evaluated. RESULTS: Antibiotic elution patterns were similar for all groups. Day
      1 elution for groups containing metronidazole or gentamicin individually
      represented a mean 63%-66% and 79%, respectively, of the 21-day total.
      Approximately 50% of the day 1 elution occurred during the first hour. The
      elution of metronidazole was dose dependent. The elution of metronidazole (day 3
      21) and gentamicin (all days) was significantly greater when metronidazole and
      gentamicin were combined (P <.05). The addition of metronidazole delayed
      polymerization of PMMA. Neither polymerization nor copolymerization of
      metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of
      beads containing metronidazole significantly affected antimicrobial bioactivity.
      CONCLUSIONS: Metronidazole elution from PMMA was dose dependent. Copolymerization
      of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of
      elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is
      not practical, but sterilization and storage for 2 months should not affect
      efficacy. CLINICAL RELEVANCE: The local delivery of biologically active
      metronidazole and gentamicin by elution from PMMA is feasible.

PMID- 12784203
TI  - Evaluation of a nontoxic rigid polymer as connecting bar in external skeletal
      fixators.
AB  - OBJECTIVE: To investigate the mechanical characteristics of a nontoxic, low-cost,
      rigid polymer (RP) and to compare the structural and mechanical properties of a
      full-frame external skeletal fixator (ESF) with either RP connecting bars,
      polymethylmethacrylate (PMMA) connecting bars, or stainless-steel (SS) clamps and
      connecting bars. STUDY DESIGN: In vitro mechanical evaluation. METHODS:
      Mechanical properties were assessed using an in vitro bone fracture model with a
      bilateral uniplanar ESF (type II). Identical ESF were built with connecting bars
      using RP (n = 8), PMMA (n = 8), and SS connecting bars and clamps (System
      Meynard; n = 3). Nondestructive mechanical tests were performed in uniaxial
      compression (AC) and craniocaudal (CC) 4-point bending, as well as fatigue AC.
      Composite stiffness for each specimen and for each loading mode was calculated
      from 6 replicate measures using the slope of the load displacement curve at small
      displacements. RESULTS: RP, PMMA, and SS ESF constructs yielded mean +/- SD
      composite stiffness values of 227 +/- 15, 381 +/- 30, and 394 +/- 9 N/mm in AC
      and of 35 +/- 2, 24 +/- 2, and 15 +/- 0 N/mm in CC, respectively. CONCLUSIONS:
      Structural and mechanical properties of RP are satisfactorily rigid and fatigue
      resistant for its use as a connecting bar in ESF. CLINICAL RELEVANCE: RP
      connecting bars in an ESF are a reliable, versatile, nontoxic and inexpensive
      option for the veterinary surgeon.

PMID- 12784204
TI  - Histologic changes in ruptured canine cranial cruciate ligament.
AB  - OBJECTIVES: To determine changes to the cells and collagenous and amorphous
      extracellular matrix (ECM) structure in ruptured canine cranial cruciate
      ligaments (CCL). STUDY DESIGN: Prospective clinical study. ANIMALS: CCL specimens
      obtained from 29 dogs with ruptured CCL and 6 young dogs with intact CCL.
      METHODS: Ligament fibroblast number density and phenotype were determined in the
      core and epiligamentous regions. ECM birefringence and crimp structure in the
      core region were also studied. RESULTS: Loss of fibroblasts from the core region
      of ruptured CCL was seen (P <.001), whereas, in the epiligamentous region, cell
      number densities were similar in ruptured and intact CCL (P =.7). In ruptured
      CCL, numbers of typical ligament fibroblasts (fusiform and ovoid cells) were
      decreased, and numbers of cells exhibiting chondroid transformation (spheroid
      cells) were increased in the core region (P <.001). Expansion of the volume of
      the epiligamentous region was also seen, although bridging scar tissue was not
      seen between the ends of ruptured CCL. The structure of the ECM collagen in the
      core region was extensively disrupted in ruptured CCL. This was, in part, because
      of decreased birefringence and elongation of the crimp in the remaining collagen
      fibers when compared with intact CCL (P <.01). CONCLUSIONS: Extensive alterations
      to the cell populations and collagenous ECM structure were seen in ruptured CCL.
      Although a proliferative epiligamentous repair response was seen in ruptured CCL,
      there was a lack of any bridging scar between the ruptured ends of the CCL.
      CLINICAL RELEVANCE: The cellular and ECM changes in ruptured CCL that we have
      described appear to result from the cumulative effects of remodeling and
      adaptation to mechanical loading and microinjury. Treatment of early cruciate
      disease in dogs will need to inhibit or reverse these progressive changes to CCL
      tissue, which are directly associated with partial or complete structural failure
      of the CCL under conditions of normal activity.

PMID- 12784205
TI  - Tenoscopic release of the equine carpal canal.
AB  - OBJECTIVE: To develop a tenoscopic method to divide the carpal flexor retinaculum
      and decompress the carpal canal. STUDY DESIGN: Cadaver specimen study and
      prospective trial. ANIMALS: Twelve cadaveric limbs, 4 clinically normal horses,
      and 2 clinically affected horses. Methods-A tenoscopic approach to the
      proximolateral aspect of the carpal sheath was used to identify and facilitate
      endoscopic division of the inner and outer layers of the carpal flexor
      retinaculum in cadaver limbs. The technique was further evaluated in 4 normal and
      2 clinically affected horses. RESULTS: Anatomic dissection, intraoperative
      observation, necropsy, histologic evaluation, and both short- and long-term
      clinical follow-up indicate that a tenoscopic approach that divides the inner
      layer of the carpal retinaculum can successfully decompress the equine carpal
      canal. No iatrogenic damage to surrounding structures was evident, division of
      the retinaculum was adequate and permanent, and clinical morbidity was
      negligible. Resolution of effusion was evident in both clinical cases of carpal
      canal syndrome and lameness resolved in the 1 horse in which long-term follow-up
      was possible. CONCLUSIONS: Tenoscopic release of the carpal flexor retinaculum
      could provide a minimally invasive method to quickly, safely, and effectively
      decompress the carpal canal. CLINICAL RELEVANCE: Tensocopic release of the carpal
      flexor retinaculum is a safe alternative to open division of the retinaculum to
      decompress the carpal canal in horses with carpal canal syndrome.

PMID- 12784206
TI  - Retrospective analysis of canine miniature total hip prostheses.
AB  - OBJECTIVE: To determine the practicality and clinical outcome of miniature total
      hip replacement (THR) in dogs. STUDY DESIGN: Retrospective study. Sample
      Population- Seventeen client-owned dogs that had miniature THR. METHODS: Patient
      data surveyed included signalment, body weight, diagnosis, implant size, surgical
      technique, and intraoperative and postoperative complications. Radiographic
      evaluation included angle of lateral opening of the acetabular component, implant
      positioning, cement mantle quality, and femoral displacement measurement and
      ratio. Client questionnaire and orthopedic examination were used to obtain long
      term follow-up information. RESULTS: Miniature THR was performed to address hip
      dysplasia and secondary osteoarthritis. In 1 dog, a staged bilateral procedure
      was performed. Mean body weight was 19 kg (range, 12 to 25 kg). Penetration or
      fissure of the femoral cortex was the most common intraoperative complication and
      occurred in 3 dogs. In 3 dogs, there was excessive coxofemoral laxity after
      reduction of the prosthesis. This instability was addressed specifically in 2
      dogs by capsulorrhaphy or capsular prosthesis. Postoperative convalescent
      complications (craniodorsal luxation, 2 dogs; acetabular cup displacement, 1 dog)
      were related to surgical errors. Aseptic loosening of the femoral implant was
      diagnosed in 1 dog at 18 months. Mean follow-up time was 17 months (range, 4 to
      42 months). Fifteen of 18 (83%) miniature THRs had good or excellent outcomes.
      CONCLUSIONS: Miniature THR should be considered a satisfactory alternative to
      femoral head and neck ostectomy in medium-size dogs affected by hip dysplasia and
      secondary osteoarthritis. The population of medium-size dogs that might derive
      more benefit from THR than FHO has yet to be defined. CLINICAL RELEVANCE:
      Miniature THR is a viable treatment option in medium-size dogs with hip
      dysplasia.

PMID- 12784207
TI  - Inflammatory polyps of the middle ear in 5 dogs.
AB  - OBJECTIVE: To describe inflammatory polyps of the middle ear in 5 dogs. STUDY
      DESIGN: Case series. ANIMALS: Five dogs with ear disease. METHODS: Medical
      records (1995-2001) were reviewed to identify dogs with inflammatory polyps of
      the middle ear. Signalment, clinical signs, ancillary diagnostic procedures,
      treatment, postoperative complications, and outcome were recorded. Owners and
      referring veterinarians were contacted to document outcome. RESULTS: Dogs with
      inflammatory polyps of the middle ear were male and aged 4 to 13 years. Two dogs
      had bilateral polyps, whereas 3 had unilateral polyps. The most common clinical
      presentation was otitis externa and media, with radiographic evidence of otitis
      media. Polyps were treated by ventral bulla osteotomy (VBO) in 1 dog and total
      ear canal ablation with lateral bulla osteotomy (TECA-LBO) in 4 dogs. Polyps
      consisted of a fibrovascular stroma infiltrated with neutrophils, macrophages,
      lymphocytes, and plasma cells. The overlying epithelium was frequently ulcerated.
      Immediate postoperative complications included a seroma after VBO (1 dog) and
      transient unilateral facial nerve paralysis after bilateral TECA-LBO (1 dog). No
      recurrence occurred within 9 to 69 months. CONCLUSIONS: Unilateral or bilateral,
      inflammatory polyps can occur in the middle ear of dogs in association with
      otitis externa and media. No recurrence occurred after surgical removal of the
      polyps. CLINICAL RELEVANCE: Inflammatory polyps of the middle ear in dogs can be
      a cause of otitis externa/media. Surgical removal of aural polyps has a good
      prognosis.

PMID- 12784208
TI  - Proposed amino acid sequence and the 1.63 A X-ray crystal structure of a plant
      cysteine protease, ervatamin B: some insights into the structural basis of its
      stability and substrate specificity.
AB  - The crystal structure of a cysteine protease ervatamin B, isolated from the
      medicinal plant Ervatamia coronaria, has been determined at 1.63 A. The unknown
      primary structure of the enzyme could also be traced from the high-quality
      electron density map. The final refined model, consisting of 215 amino acid
      residues, 208 water molecules, and a thiosulfate ligand molecule, has a
      crystallographic R-factor of 15.9% and a free R-factor of 18.2% for F >
      2sigma(F). The protein belongs to the papain superfamily of cysteine proteases
      and has some unique properties compared to other members of the family. Though
      the overall fold of the structure, comprising two domains, is similar to the
      others, a few natural substitutions of conserved amino acid residues at the
      interdomain cleft of ervatamin B are expected to increase the stability of the
      protein. The substitution of a lysine residue by an arginine (residue 177) in
      this region of the protein may be important, because Lys --> Arg substitution is
      reported to increase the stability of proteins. Another substitution in this
      cleft region that helps to hold the domains together through hydrogen bonds is
      Ser36, replacing a conserved glycine residue in the others. There are also some
      substitutions in and around the active site cleft. Residues Tyr67, Pro68, Val157,
      and Ser205 in papain are replaced by Trp67, Met68, Gln156, and Leu208,
      respectively, in ervatamin B, which reduces the volume of the S2 subsite to
      almost one-fourth that of papain, and this in turn alters the substrate
      specificity of the enzyme.

PMID- 12784209
TI  - Ultraviolet illumination-induced reduction of alpha-lactalbumin disulfide
      bridges.
AB  - Prolonged exposure of Ca(2+)-loaded or Ca(2+)-depleted human alpha-lactalbumin to
      ultraviolet light (270-290 nm, 1 mW/cm(2), for 2 to 4 h) results in a 10-nm red
      shift of its tryptophan fluorescence spectrum. Gel chromatography of the UV
      illuminated samples reveals two non-native protein forms: (1) a component with a
      red-shifted tryptophan fluorescence spectrum; and (2) a component with kynurenine
      like fluorescent properties. The first component has from 0.6 to 0.9 free DTNB
      reactive SH groups per protein molecule, which are absent in the native protein
      and is characterized by slightly lowered Ca(2+)-affinity (2 x 10(8) M(-1) versus
      8 x 10(8) M(-1) for the native protein) and absence of observable thermal
      transition. The second component corresponds to the protein with photochemically
      modified tryptophan residues. It is assumed that the UV excitation of tryptophan
      residue(s) in alpha-lactalbumin is followed by a transfer of electrons to the
      Sbond;S bonds, resulting in their reduction. Mass spectrometry data obtained for
      trypsin-fragmented UV-illuminated alpha-lactalbumin with acrylodan-modified free
      thiol groups reveal the reduction of the 61-77 and 73-91 disulfide bridges. The
      effect observed has to be taken into account in any UV-region spectral studies of
      alpha-lactalbumin.

PMID- 12784210
TI  - Hidden Markov models that use predicted local structure for fold recognition:
      alphabets of backbone geometry.
AB  - An important problem in computational biology is predicting the structure of the
      large number of putative proteins discovered by genome sequencing projects. Fold
      recognition methods attempt to solve the problem by relating the target proteins
      to known structures, searching for template proteins homologous to the target.
      Remote homologs that may have significant structural similarity are often not
      detectable by sequence similarities alone. To address this, we incorporated
      predicted local structure, a generalization of secondary structure, into two
      track profile hidden Markov models (HMMs). We did not rely on a simple helix
      strand-coil definition of secondary structure, but experimented with a variety of
      local structure descriptions, following a principled protocol to establish which
      descriptions are most useful for improving fold recognition and alignment
      quality. On a test set of 1298 nonhomologous proteins, HMMs incorporating a 3
      letter STRIDE alphabet improved fold recognition accuracy by 15% over amino-acid
      only HMMs and 23% over PSI-BLAST, measured by ROC-65 numbers. We compared two
      track HMMs to amino-acid-only HMMs on a difficult alignment test set of 200
      protein pairs (structurally similar with 3-24% sequence identity). HMMs with a 6
      letter STRIDE secondary track improved alignment quality by 62%, relative to DALI
      structural alignments, while HMMs with an STR track (an expanded DSSP alphabet
      that subdivides strands into six states) improved by 40% relative to CE.

PMID- 12784211
TI  - Analysis of the differences in the folding kinetics of structurally homologous
      proteins based on predictions of the gross features of residue contacts.
AB  - It is a general notion that proteins with very similar three-dimensional
      structures would show very similar folding kinetics. However, recent studies
      reveal that the folding kinetic properties of some proteins contradict this
      thought (i.e., the members in a same protein family fold through different
      pathways). For example, it has been reported that some beta-proteins in the
      intracellular lipid-binding protein family fold through quite different pathways
      (Burns et al., Proteins 1998;33:107-118). Similar differences in folding kinetics
      are also observed in the members of the globin family (Nishimura et al., Nat
      Struct Biol 2000;7:679-686). In our study, we examine the possibility of
      predicting qualitative differences in folding kinetics of the intracellular lipid
      binding proteins and two globin proteins (i.e., myoglobin and leghemoglobin). The
      problem is tackled by means of a contact map based on the average distance
      statistics between residues, the Average Distance Map (ADM), as constructed from
      sequence. The ADMs for the three proteins show overall similarity, but some local
      differences among maps are also observed. Our results demonstrate that some
      properties of the protein folding kinetics are consistent with local differences
      in the ADMs. We also discuss the general possibility of predicting folding
      kinetics from sequence information.

PMID- 12784212
TI  - Fold recognition with minimal gaps.
AB  - Here we present a simplified form of threading that uses only a 20 x 20 two-body
      residue-based potential and restricted number of gaps. Despite its simplicity and
      transparency the Monte Carlo-based threading algorithm performs very well in a
      rigorous test of fold recognition. The results suggest that by simplifying and
      constraining the decoy space, one can achieve better fold recognition. Fold
      recognition results are compared with and supplemented by a PSI-BLAST search. The
      statistical significance of threading results is rigorously evaluated from
      statistics of extremes by comparison with optimal alignments of a large set of
      randomly shuffled sequences. The statistical theory, based on the Random Energy
      Model, yields a cumulative statistical parameter, epsilon, that attests to the
      likelihood of correct fold recognition. A large epsilon indicates a significant
      energy gap between the optimal alignment and decoy alignments and, consequently,
      a high probability that the fold is correctly recognized. For a particular number
      of gaps, the epsilon parameter reaches its maximal value, and the fold is
      recognized. As the number of gaps further increases, the likelihood of correct
      fold recognition drops off. This is because the decoy space is small when gaps
      are restricted to a small number, but the native alignment is still well
      approximated, whereas unrestricted increase of the number of gaps leads to rapid
      growth of the number of decoys and their statistical dominance over the correct
      alignment. It is shown that best results are obtained when a combination of one-,
      two-, and three-gap threading is used. To this end, use of the epsilon parameter
      is crucial for rigorous comparison of results across the different decoy spaces
      belonging to a different number of gaps.

PMID- 12784213
TI  - Insights into nonspecific binding of homeodomains from a structure of MATalpha2
      bound to DNA.
AB  - The 2.1-A resolution crystal structure of the MATalpha2 homeodomain bound to DNA
      reveals the unexpected presence of two nonspecifically bound alpha2 homeodomains,
      in addition to the two alpha2 homeodomains bound to canonical alpha2 binding
      sites. One of the extra homeodomains makes few base-specific contacts, while the
      other extra homeodomain binds to DNA in a previously unobserved manner. This
      unusually bound homeodomain is rotated on the DNA, making possible major groove
      contacts by side-chains that normally do not contact the DNA. This alternate
      docking may represent one way in which homeodomains sample nonspecific DNA
      sequences.

PMID- 12784214
TI  - Endogenous tryptophan residues of cAPK regulatory subunit type IIbeta reveal
      local variations in environments and dynamics.
AB  - The amino terminal dimerization/docking domain and the two-tandem, carboxy
      terminal cAMP-binding domains (A and B) of cAMP-dependent protein kinase
      regulatory (R) subunits are connected by a variable linker region. In addition to
      providing a docking site for the catalytic subunit, the linker region is a major
      source of sequence diversity between the R-subunit isoforms. The RIIbeta isoform
      uniquely contains two endogenous tryptophan residues, one at position 58 in the
      linker region and the other at position 243 in cAMP-binding domain A, which can
      act as intrinsic reporter groups of their dynamics and microenvironment. Two
      single-point mutations, W58F and W243F, allowed the local environment of each Trp
      to be probed using steady-state and time-resolved fluorescence techniques. We
      report that: (a) the tryptophan fluorescence of the wild-type protein largely
      reflects Trp243 emission; (2) cAMP selectively quenches Trp243 and thus acts as a
      cAMP sensor; (3) Trp58 resides in a highly solvated, unstructured, and mobile
      region of the protein; and (4) Trp243 resides in a stable, folded domain and is
      relatively buried and rigid within the domain. The use of endogenous Trp residues
      presents a non-perturbing method for studying R-subunit subdomain characteristics
      in addition to providing the first biophysical data on the RIIbeta linker region.

PMID- 12784215
TI  - Data mining crystallization databases: knowledge-based approaches to optimize
      protein crystal screens.
AB  - Protein crystallization is a major bottleneck in protein X-ray crystallography,
      the workhorse of most structural proteomics projects. Because the principles that
      govern protein crystallization are too poorly understood to allow them to be used
      in a strongly predictive sense, the most common crystallization strategy entails
      screening a wide variety of solution conditions to identify the small subset that
      will support crystal nucleation and growth. We tested the hypothesis that more
      efficient crystallization strategies could be formulated by extracting useful
      patterns and correlations from the large data sets of crystallization trials
      created in structural proteomics projects. A database of crystallization
      conditions was constructed for 755 different proteins purified and crystallized
      under uniform conditions. Forty-five percent of the proteins formed crystals.
      Data mining identified the conditions that crystallize the most proteins,
      revealed that many conditions are highly correlated in their behavior, and showed
      that the crystallization success rate is markedly dependent on the organism from
      which proteins derive. Of the proteins that crystallized in a 48-condition
      experiment, 60% could be crystallized in as few as 6 conditions and 94% in 24
      conditions. Consideration of the full range of information coming from crystal
      screening trials allows one to design screens that are maximally productive while
      consuming minimal resources, and also suggests further useful conditions for
      extending existing screens.

PMID- 12784216
TI  - Scaling law in sizes of protein sequence families: from super-families to orphan
      genes.
AB  - It has been observed that the size of protein sequence families is unevenly
      distributed, with few super families with a large number of members and many
      "orphan" proteins that do not belong to any family. Here it is shown that the
      distribution of sizes of protein families in different databases and
      classifications (Protomap, Prodom, Cog) follows a power-law behavior with similar
      scaling exponents, which is characteristic of self-organizing systems. Since
      large databases are used in this study, a more detailed analysis of the data than
      in previous studies was possible. Hence, it is shown that the size distribution
      is governed by two exponents, different for the super families and the orphan
      proteins. A simple model of protein evolution is proposed, in which proteins are
      dynamically generated and clustered into families. The model yields a scaling
      behavior very similar to the distribution observed in the actual sequence
      databases, including the two distinct regimes for the large and small families,
      and thus suggests that the existence of "super families" of proteins and "orphan"
      proteins are two manifestations of the same evolutionary process.

PMID- 12784217
TI  - Generation of accurate protein loop conformations through low-barrier molecular
      dynamics.
AB  - Prediction and refinement of protein loop structures are important and
      challenging tasks for which no general solution has been found. In addition to
      the accuracy of scoring functions, the main problems reside in (1) insufficient
      statistical sampling and (2) crossing energy barriers that impede conformational
      rearrangements of the loop. We approach these two issues by using "low-barrier
      molecular dynamics," a combination of energy smoothing techniques. To address
      statistical sampling, locally enhanced sampling (LES) is used to produce multiple
      copies of the loop, thus improving statistics and reducing energy barriers. We
      introduce a novel extension of LES that can improve local sampling even further
      through hierarchical subdivision of copies. Even though LES reduces energy
      barriers, it cannot provide for crossing infinite barriers, which can be
      problematic when substantial rearrangement of residues is necessary. To permit
      this kind of loop residue repacking, a "soft-core" potential energy function is
      introduced, so that atomic overlaps are temporarily allowed. We tested this new
      combined methodology to a loop in anti-influenza antibody Fab 17/9 (7 residues
      long) and to another loop in the antiprogesterone antibody DB3 (8 residues). In
      both cases, starting from random conformations, we were able to locate correct
      loop structures (including sidechain orientations) with heavy-atom root-mean
      square deviation (fit to the nonloop region) of approximately 1.1 A in Fab 17/9
      and approximately 1.8 A in DB3. We show that the combination of LES and soft-core
      potential substantially improves sampling compared to regular molecular dynamics.
      Moreover, the sampling improvement obtained with this combined approach is
      significantly better than that provided by either of the two methods alone.

PMID- 12784218
TI  - The nature of the turn in omega loops of proteins.
AB  - An analysis of Omega loops in a nonredundant set of protein structures from the
      Protein Data Bank has been carried out to determine the nature of the "turn
      elements" present. Because Omega loops essentially reverse their direction in
      three-dimensional space, this analysis was made with respect to four turn
      elements identified as (1) Gly; (2) Pro; (3) a residue with alpha-helical phi,psi
      angles, termed a helical residue; and (4) a cis peptide. A set of 1079 Omega
      loops from a set of 680 proteins were used for the analysis. Apart from other
      criteria that define Omega loops, the selection of an Omega loop from a cluster
      of loops is based on an exposure index. In this study, analyses have been made
      with two sets of data: (1) Omega loops arising from a minimum exposure index
      indicative of a less exposed loop (xmin set) and (2) Omega loops with a maximum
      exposure index indicative of a relatively exposed loop (xmax set). Overall
      residue preferences and positional preferences have been examined. Positions of
      the turn elements for Omega loops of varying length have also been studied.
      Specific positional preferences are observed for particular turn elements with
      regard to the length of Omega loops. Analysis in terms of the turn elements can
      provide guidelines for modeling of loops in proteins. Apart from Pro, which has
      the natural tendency to form cis peptide bonds, a higher occurrence of non-Pro
      cis peptide bonds is observed. Torsion angles in Omega loops also indicate the
      occurrence of a large number of residues with helical phi,psi angles, necessary
      for the turn in the loop structures.

PMID- 12784219
TI  - Static and dynamic water molecules in Cu,Zn superoxide dismutase.
AB  - Understanding protein hydration is a crucial, and often underestimated issue, in
      unraveling protein function. Molecular dynamics (MD) computer simulation can
      provide a microscopic description of the water behavior. We have applied such a
      simulative approach to dimeric Photobacterium leiognathi Cu,Zn superoxide
      dismutase, comparing the water molecule sites determined using 1.0 ns MD
      simulation with those detected by X-ray crystallography. Of the water molecules
      detected by the two techniques, 20% fall at common sites. These are evenly
      distributed over the protein surface and located around crevices, which represent
      the preferred hydration sites. The water mean residence time, estimated by means
      of a survival probability function on a given protein hydration shell, is
      relatively short and increases for low accessibility sites constituted by polar
      atoms. Water molecules trapped in the dimeric protein intersubunit cavity, as
      identified in the crystal structure, display a trajectory mainly confined within
      the cavity. The simulation shows that these water molecules are characterized by
      relatively short residence times, because they continuously change from one site
      to another within the cavity, thus hinting at the absence of any relationship
      between spatial and temporal order for solvent molecules in proximity of protein
      surface.

PMID- 12784220
TI  - Crystal structure of the type II 3-dehydroquinase from Helicobacter pylori.

PMID- 12784222
TI  - Overview: Infants and children with hearing loss-part I.

PMID- 12784224
TI  - Quality monitoring for early hearing detection and intervention programs to
      optimize performance.
AB  - The purpose of this chapter is to review the principles of quality monitoring for
      newborn screening programs at both a hospital and a public health level. The
      focus is on quality assurance in Early Hearing Detection and Intervention (EHDI).
      The chapter addresses the need for a systems approach to quality, beginning with
      the birth screening, moving to follow-up re-screening and on to confirmatory
      evaluations and life-long intervention and management for the infants identified
      with permanent hearing loss. Benchmarks are identified to assist those involved
      in establishing programs or in improving program performance. As the use of
      electronic information systems in EHDI becomes widespread, the importance of
      strict computer-based logic rules to assure patient privacy is addressed.

PMID- 12784223
TI  - Screening methods: current status.
AB  - Two technologies are currently used to screen newborn infants for hearing,
      auditory brainstem response (ABR), and otoacoustic emissions (OAEs). Each
      technology is based on detecting the infant's physiologic response to auditory
      stimulation. ABR is a short-latency auditory evoked response originating from
      eighth nerve and brainstem auditory pathway structures and detected by scalp
      surface electrodes. OAEs are auditory signals generated by cochlear outer hair
      cells in response to acoustic stimulation and detected by a miniature microphone
      coupled to the infant's ear. Although each technique requires specific sound
      generation and response recording technologies, advances in computerized stimulus
      delivery and response detection algorithms allow these tests to be performed by
      trained technicians or volunteers under the supervision of an audiologist.
      Results of test performance, and the advantages and disadvantages of each
      technique are described.

PMID- 12784226
TI  - Family perceptions of early hearing, detection, and intervention systems:
      listening to and learning from families.
AB  - As universal newborn hearing systems (screening, diagnosis, intervention) are
      being established around the world, the success of children who are identified to
      be deaf and hard of hearing is critically impacted by parent's reactions,
      acceptance, and advocacy for their child. It is imperative for professionals who
      are creating systems for Early Hearing, Detection, and Intervention to understand
      and learn from families' experiences in order to improve this process. This
      manuscript will identify the areas in which parents have spoken out about the
      professionals they have encountered through the system: what parents wish for in
      a healthy, productive relationship with professionals; and how parents can play a
      part in advocating for a system in which families needs are met so that infants
      identified to be deaf or hard of hearing can reach their full potential.

PMID- 12784225
TI  - The current status of EHDI programs in the United States.
AB  - The importance of identifying congenital hearing loss during the first few months
      of life has been recognized for almost 60 years. Unfortunately, until more
      effective newborn hearing screening equipment and procedures were developed in
      the late 1980s, it was not practical to implement programs for identifying
      hearing loss during the first few months of life. This paper reviews the
      activities implemented by the federal government in the last 15 years to promote
      more effective Early Hearing Detection and Intervention (EHDI) programs, and
      summarizes legislation passed by states related to universal newborn hearing
      screening. In surveys conducted in 1998 and 2001, State EHDI Coordinators were
      asked to rate the degree to which various issues were obstacles to implementing
      effective EHDI programs. The most serious obstacles are the shortage of qualified
      pediatric audiologists, inadequate reimbursement for screening and diagnosis, and
      lack of knowledge among primary health care providers about EHDI issues.
      Opposition to EHDI programs by hospital administrators was rated substantially
      lower in 2001 than in 1998. State EHDI Coordinators were also surveyed about how
      well their EHDI program is addressing issues related to screening, diagnosis,
      early intervention, linkages to medical home providers, tracking and data
      management, and family support programs. Although substantial progress has been
      made, many gaps remain with current EHDI programs.

PMID- 12784227
TI  - The otolaryngologist's role in management of hearing loss in infancy and
      childhood.
AB  - This article reviews the role of the otolaryngologist-head and neck surgeon-in
      the diagnosis and treatment of hearing loss in infants and young children. The
      otolaryngologist is well-versed in the anatomy, physiology, and pathophysiology
      of the auditory system, as well as the craniofacial syndromes that can involve
      the head and neck in combination with deafness. In this paper, the various causes
      of congenital hearing loss are described, as well as the steps required for
      proper diagnosis. Finally, surgeries used by otolaryngologists to treat childhood
      hearing loss, their indications, and outcomes, are discussed.

PMID- 12784228
TI  - Cost-effectiveness and test-performance factors in relation to universal newborn
      hearing screening.
AB  - The first portion of this paper reviews current understanding of the cost of
      universal newborn hearing screening (UNHS), including capital and operating
      expenses, as well as the costs for follow-up testing on infants who do not pass
      the hearing screening test in the perinatal period. Capital expenses include the
      cost of equipment. Operating expenses include the costs for disposables and
      personnel. Follow-up costs relate to the diagnostic testing that must be
      performed in order to determine hearing status in those infants who do not pass
      the newborn hearing screening test. This section is followed by a more
      theoretical approach, in which test performance, prevalence, program costs, and
      "costs of hearing loss" are combined in a model that includes all costs of
      hearing loss, including screening, follow-up testing, and costs (benefits)
      associated with identifying hearing loss early in life. While some of the model's
      cost/benefit assumptions may be incorrect, the general approach of taking into
      account both costs and benefits provides a framework for evaluating the utility
      of UNHS in a more global manner. Model assumptions (costs, benefits, prevalence,
      sensitivity, specificity) can be changed to values deemed more appropriate, but
      the general approach is still informative. With the present assumptions, it is
      shown that initially, the costs of UNHS exceed its benefits. However, after only
      four years of operation, UNHS programs will result in a net savings to society.
      These savings increase rapidly, reaching a maximum annual benefit of seven
      billion dollars 75 years after initiation of the program, which is also the
      societal benefit for all years thereafter.

PMID- 12784229
TI  - The genetics of deafness.
AB  - Deafness is an etiologically heterogeneous trait with many known genetic and
      environmental causes. Genetic factors account for at least half of all cases of
      profound congenital deafness, and can be classified by the mode of inheritance
      and the presence or absence of characteristic clinical features that may permit
      the diagnosis of a specific form of syndromic deafness. The identification of
      more than 120 independent genes for deafness has provided profound new insights
      into the pathophysiology of hearing, as well as many unexpected surprises.
      Although a large number of genes can clearly cause deafness, recessive mutations
      at a single locus, GJB2 or Connexin 26, account for more than half of all genetic
      cases in some, but not all populations. The high frequency may well be related to
      the greatly improved social, educational, and economic circumstances of the deaf
      that began with the introduction of sign language 300-400 years ago, along with a
      high frequency of marriages among the deaf in many countries. Similar mechanisms
      may account for the rapid fixation of genes for speech after the first mutations
      appeared 50,000-100,000 years ago. Molecular studies have shown that mutations
      involving several different loci may be the cause for the same form of syndromic
      deafness. Even within a single locus, different mutations can have profoundly
      different effects, leading to a different pattern of inheritance in some cases,
      or isolated hearing loss without the characteristic syndromic features in others.
      Most cases of genetic deafness result from mutations at a single locus, but an
      increasing number of examples are being recognized in which recessive mutations
      at two loci are involved. For example, digenic interactions are now known to be
      an important cause of deafness in individuals who carry a single mutation at the
      Connexin 26 locus along with a deletion involving the functionally related
      Connexin 30 locus. This mechanism complicates genetic evaluation and counseling,
      but provides a satisfying explanation for Connexin 26 heterozygotes who, for
      previously unknown reasons, are deaf. A specific genetic diagnosis can sometimes
      be of great clinical importance, as in the case of the mitochondrial A1555G
      mutation which causes gene carriers to be exquisitely sensitive to the ototoxic
      effects of aminoglycosides. This potentially preventable genetic-environmental
      interaction was the most common cause of genetic deafness in countries where
      these antibiotics were used indiscriminately in the past. Advances in genetic
      knowledge along with the use of cochlear implants have posed unique ethical
      dilemmas for society as well as the deaf community. Since most deaf children are
      born to hearing parents, it seems likely that deaf culture, and intermarriages
      among those born with deafness will recede during this century. Will future
      critics view this as one of the medical triumphs of the 21(st) Century, or as an
      egregious example of cultural genocide? On the other hand, genetics can provide
      empowering knowledge to the deaf community that for the first time can allow many
      deaf couples to know whether their children will be hearing or deaf even before
      they are conceived.

PMID- 12784230
TI  - Nongenetic causes of hearing loss.
AB  - Nongenetic as well as genetic etiologies must be explored in the child with
      identified hearing loss. Graduates of the neonatal intensive care unit are at
      increased risk for developing hearing loss due to hypoxia, hyperbilirubinemia,
      very low birth weight, and ototoxic medications. Although meningitis has
      decreased in frequency, it is still a risk factor for hearing loss.
      Cytomegalovirus remains the most common congenital infection and a relatively
      common etiology of hearing loss, which can be progressive. Preventable causes of
      hearing loss include those caused by head trauma, noise, and ototoxic
      medications. Identification of the etiology of hearing loss can facilitate the
      development of a treatment and management plan.

PMID- 12784231
TI  - Certification in neurodevelopmental disabilities: the development of a new
      subspecialty and results of the initial examinations.
AB  - The American Board of Psychiatry and Neurology, in collaboration with the
      American Board of Pediatrics, administered the first Subspecialty Certification
      Examination in Neurodevelopmental Disabilities to 190 candidates on April 3,
      2001, and the second to 80 candidates on April 9, 2002. This report describes the
      history of the certifying examination including the process of its development
      and the results of the first and second examination administrations. The purpose
      of the Certification Examination in Neurodevelopmental Disabilities is to assess
      knowledge of qualified candidates in the subspecialty. A committee comprised of
      child neurologists and pediatricians developed this examination. Of the 190
      pediatricians (n = 169) and child neurologists (n = 21) who completed the
      examination in 2001, 157 (83%) passed the examination. The second group of
      examinees included 68 pediatricians and 12 child neurologists, and the pass rate
      was 70%. The 213 candidates certified to date have received ten-year time-limited
      certificates that may be renewed by recertification process beginning in 2010.
      After the "grandfathering period," candidates for the examination must complete
      ACGME-approved training programs in the subspecialty.

PMID- 12784232
TI  - Efficacy of radiation therapy in the local control of desmoplastic malignant
      melanoma.
AB  - BACKGROUND: Desmoplastic malignant melanoma (DMM) is a rare variant of malignant
      melanoma with high local recurrence rate after surgical excision. We performed a
      retrospective review to address the role of radiation therapy in local control of
      this tumor. METHODS: Between 1976 and 1997, 44 patients with the pathologic
      diagnosis of DMM were registered at our tumor registry. Fourteen patients
      received postoperative RT, and one patient received preoperative RT. Three of the
      irradiated lesions had gross residual or positive surgical margins. Doses ranged
      from 44 to 66 Gy. RESULTS: Sixty-eight percent of DMM lesions occurred in the
      head and neck region. Forty-eight percent (21 of 44) of patients experienced a
      local recurrence after initial excision (mean time to recurrence, 12 months).
      Local failure in head and neck was 46% (14 of 30). Clark level, primary site, and
      neurotropism did not predict local recurrence; the Clark level predicted distant
      metastasis. No viable tumor was found in the surgical specimen of the patient who
      received preoperative RT. None of 15 patients who received adjuvant irradiation
      had any additional recurrences (mean follow-up, 64.7 months). By contrast, four
      of seven patients with history of recurrence who did not receive RT had local
      relapse (p =.005). The incidence of distant metastasis did not reach statistical
      significance between the irradiated and nonirradiated groups. CONCLUSIONS: The
      high rate of local recurrence of DMM after surgical resection is dramatically
      reduced by adjuvant radiation therapy. We recommend adjuvant postoperative
      radiation therapy as a part of treatment of DMM.

PMID- 12784233
TI  - Medical malpractice and the thyroid gland.
AB  - BACKGROUND: A medical malpractice litigation "crisis" exists in this country.
      Analyzing litigation trends through verdict summaries may help understand causes.
      METHODS: Jury verdict reviews from 1987-2000 were obtained from a computerized
      database. Reviews compile data on defendants, plaintiffs, allegations of
      wrongdoing, and verdict summaries. RESULTS: Thirty suits from nine states
      occurred. Plaintiffs were women in 80% of the cases, with a median age of 41.
      Fifty percent of patients (15 of 30) had a bad outcome, (9 of 30 dead, 4 of 30
      with neurologic deficits, 1 blind, and 1 alive with cancer). Thirty percent
      alleged surgical complications, mostly recurrent laryngeal nerve injury, and 75%
      of cancer patients alleged a delay, either through falsely negative biopsies or
      no biopsy taken. Respiratory events occurred in 43% and frequently resulted in
      large awards. CONCLUSIONS: The liberal use of fine-needle aspiration and
      documentation of surgical risks may help reduce litigation. Complications and bad
      outcomes do not indicate negligence. Analysis may contribute to risk management
      strategies or litigation reform.

PMID- 12784234
TI  - Xerostomia: 12-month changes in saliva production and its relationship to
      perception and performance of swallow function, oral intake, and diet after
      chemoradiation.
AB  - BACKGROUND: Previous investigators have found permanent changes in saliva
      production after chemoradiation but have not examined these in relation to
      swallowing measures, diet changes, and patient comfort over time. METHODS: Thirty
      patients with advanced stage cancer of the oropharynx treated with chemoradiation
      were followed with videofluoroscopic swallow studies, a measure of stimulated
      total saliva production, a questionnaire of their perception of dry mouth, and a
      questionnaire on the nature of their oral intake at pretreatment until 12 months
      after treatment. RESULTS: Saliva declined significantly from pretreatment to 12
      months. Swallowing-related complaints increased significantly over the 12 months,
      especially in patients with lower saliva weights. Diet choices increased over
      time after treatment, except crunchy foods. Swallow measures did not relate to
      saliva weight. CONCLUSIONS: Reduced saliva weight does not correlate with slowed
      or inefficient swallow. Instead, reduced saliva weight seems to change patients'
      perceptions of their swallowing ability and, on that basis, their diet choices.

PMID- 12784235
TI  - Outpatient weekly 24-hour infusional adjuvant chemotherapy of cisplatin, 5
      fluorouracil, and leucovorin for high-risk nasopharyngeal carcinoma.
AB  - BACKGROUND: Distant metastasis rather than locoregional recurrence is the major
      site of failure after adequate radiotherapy in nasopharyngeal carcinoma (NPC).
      The aim of this study is to evaluate the toxicity and survival of outpatient
      weekly 24-hour infusion adjuvant chemotherapy for NPC patients with high-risk of
      distant failure. METHODS: Our definition of high-risk NPC included patients with
      (1) 1992 AJCC staging system of N3, T4N2, or N2 with one of nodal size > 4 cm;
      (2) supraclavicular node metastasis; and (3) residual disease after radiotherapy
      or neck relapse. From August 1994 to August 1997, 41 NPC patients matching the
      preceding criteria agreed to receive weekly PFL (cisplatin 25 mg/m(2), 5
      fluorouracil 1250 mg/m(2), and leucovorin 120 mg/m(2)) adjuvant chemotherapy for
      a total of 18 weeks. Clinical data of another 88 patients with similar disease
      status who did not receive adjuvant chemotherapy during the same period were
      collected and analyzed for comparison. Survival analysis was investigated by the
      Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of
      700 weekly chemotherapy doses was delivered to 41 patients. The ratio of
      actual/planned dose delivery was 94.9%. Grade 3-4 toxicity of adjuvant
      chemotherapy included leucopenia (7.3%), anemia (2.4%), thrombocytopenia (2.4%),
      and nausea/vomiting (2.4%). After a median follow-up of 70 months, 26.8% (11 of
      41) and 47.7% (42 of 88) of patients in PFL and no adjuvant chemotherapy groups
      had distant metastasis (p =.0247). The 5-year metastasis-free survival rates were
      71.9% for the PFL group compared with 48.4% for no adjuvant chemotherapy patients
      (p =.0187). The 5-year overall survival rates were 53.7% (PFL group) and 38.3%
      (no adjuvant chemotherapy group), respectively (p =.0666). Multivariate Cox
      analysis showed PFL adjuvant chemotherapy was the independent factor that
      predicted metastasis-free survival after adjustment for other variables.
      CONCLUSIONS: Outpatient weekly 24-hour continuous infusion PFL adjuvant
      chemotherapy is a well-tolerated regimen with promising results in high-risk NPC
      patients and merits investigation in phase III studies.

PMID- 12784236
TI  - Cervical node metastases in squamous cell carcinoma of the upper aerodigestive
      tract: the significance of extracapsular spread and soft tissue deposits.
AB  - BACKGROUND: Literature regarding the prognostic significance of extracapsular
      spread and soft tissue deposits in cervical lymph node metastases of squamous
      cell carcinoma of the upper aerodigestive tract shows variable results. METHODS:
      We analyzed 215 prospectively collected neck dissections from 155 patients with
      upper aerodigestive tract squamous cell carcinoma to assess the prevalence of
      extracapsular spread and soft tissue deposits and to assess their effect on
      survival. RESULTS: Both extracapsular spread and soft tissue deposits
      significantly reduced survival (actuarial and recurrence free) compared with pN0
      necks (p <.001) and pN+ve necks without extracapsular spread (p <.0025). There
      was no statistically significant difference between pN+ve necks without soft
      tissue deposits or extracapsular spread compared with those with pN0 necks (p
      =.24). Multivariate analysis revealed comparable results. CONCLUSIONS:
      Microscopic and macroscopic extracapsular spread and soft tissue deposits are of
      prognostic significance for survival and recurrence-free survival in patients
      with upper aerodigestive tract squamous cell carcinoma.

PMID- 12784237
TI  - Identification of NY-ESO-1, MAGE-1, and MAGE-3 in head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: Certain tumor antigens have been identified that stimulate an immune
      response, thus making them targets for immunotherapy. NY-ESO-1, MAGE-1, and MAGE
      3 are such antigens. This study was undertaken to determine their presence or
      absence in head and neck squamous cell cancers and to correlate this with patient
      characteristics. METHODS: Reverse transcriptase polymerase chain reaction (RT
      PCR) and immunohistochemistry (IH) were used to identify NY-ESO-1, MAGE-1, and
      MAGE-3 in surgical specimens. Patient data (previous treatment, gender, age,
      primary site, metastasis, tumor grade, tumor stage, smoking history, and alcohol
      history) were collected by chart review and examined for correlation with
      presence or absence of antigen. RESULTS: Three tumors were found to be positive
      for NY-ESO-1 by RT-PCR. All of these tumors were also positive for MAGE-1 and
      MAGE-3. IH was only positive for NY-ESO-1 in one patient. Eighteen of the 45
      tumors (40%) were positive for MAGE-1 by RT-PCR. By IH, only six tumors were
      positive for MAGE-1. Five (83.3%) of those that were positive by IH were positive
      by RT-PCR. Twenty of the 45 tumors (44.4%) were positive for MAGE-3 by RT-PCR. By
      IH, 12 tumors were positive for MAGE-3. Nine (75%) of those positive by IH were
      also positive by RT-PCR. Overall, of the 45 tumors, 27 (60%) were positive by RT
      PCR for at least one of the antigens. None of the patient characteristics
      correlated with the presence or absence of antigen. CONCLUSIONS: There is high
      expression of MAGE-1 and MAGE-3 antigens in head and neck squamous cell
      carcinomas, whereas NY-ESO-1 is not significantly expressed. IH correlates but is
      not as sensitive as RT-PCR for detection of these antigens. There is no
      correlation between antigen expression and patient data. On the basis of the high
      levels of MAGE-1 and MAGE-3 expression, use of these antigens may serve as a
      potential approach to immunotherapy for squamous cell carcinoma from head and
      neck sources.

PMID- 12784238
TI  - Vascular endothelial growth factor C and vascular endothelial growth factor
      receptor 3 expression in squamous cell carcinomas of the head and neck.
AB  - BACKGROUND AND METHODS: VEGF proteins and their receptors are involved in tumor
      vessel neoformation. The third VEGF receptor, VEGFR3 (flt-4) is important during
      both blood vessel development and lymphatic vessel formation. Because HNSCC
      preferentially metastasizes to regional lymph nodes, we investigated the
      expression of VEGFR3 and its ligand VEGF-C in head and neck squamous cell
      carcinomas by semiquantitative RT-PCR (4 HNSCC cells lines and 6 HNSCC specimens)
      and by immunohistochemistry (18 HNSCC specimens). VEGFR3 protein expression was
      confirmed by Western blotting in four HNSCC cell lines and six HNSCC specimens.
      RESULTS: Semiquantitative mRNA analysis showed VEGF-C mRNA expression in three
      (SCC9, SCC25, LFFR) of four HNSCC cell lines and all six HNSCC specimens. VEGFR3
      mRNA was found in two HNSCC cell lines (JPPA and SCC25) and only weakly detected
      in the other two HNSCC cell lines (SCC9 and LFFR). High amounts of VEGFR3 mRNA
      were shown in all six patients' tumor specimens. VEGFR3 Western blot analysis
      yielded a distinct band at the predicted size of 210 kD in JPPA and SCC9 and
      hardly detectable bands in SCC25 and LFFR cell lines. All six HNSCC specimens
      displayed strong VEGFR3 protein bands. Immunohistochemistry in 18 HNSCC specimens
      assigned strong to mediate VEGF-C IR and minor VEGFR3 IR to tumor cells and
      strong VEGF-C and VEGFR3 IR to tumor surrounding vessels. In addition, intense
      VEGF-C immunostaining was observed on perivascular and mononuclear cells in the
      tumor surrounding stroma. Subtyping of VEGFR3+ microvascular tumor vessels
      revealed partially double immunolabeling with CD34 and flk-1, indicating a common
      origin of blood and lymphatic vessels. The expression of VEGF-C on tumor cells
      could be correlated with recurrences, and larger primary tumors had more VEGF-C
      positive vessels. CONCLUSIONS: The broad expression of VEGF C and VEGFR3 in HNSCC
      suggests involvement in tumor lymph angiogenesis and vascular angiogenesis,
      promoting tumor growth and propagation of cancer cells. This implies that
      inhibitors of lymph angiogenesis could become effective therapeutic options
      similar to classical angiogenesis inhibitors.

PMID- 12784239
TI  - The indications and outcomes in the use of osteocutaneous radial forearm free
      flap.
AB  - INTRODUCTION: Whether secondary to cancer surgery ablation or trauma, surgeons
      are faced with defects of the mandible or maxilla that would be best
      reconstructed with a thin, pliable soft tissue component and vascularized bone. A
      subset of these challenging wounds do not require the bicortical bone necessary
      to reestablish structural integrity or to retain a dental prosthesis, because the
      soft tissue needs are more critical than the bony needs. It is this niche that
      the radial forearm osteofaciocutaneous free flap (RFOFF) fulfills well. In the
      past, potential and real donor site morbidity has precluded the routine use of
      this flap. New methods to reduce this morbidity have rekindled our use of this
      flap. PROCEDURES USED: A retrospective review of patients with defects of the
      mandible or maxilla treated with the RFOFF from July 1, 1997, to December 31,
      2000, was performed. After flap harvest, the donor site was rigidly fixated. A
      skin graft was placed, and a volar splint was applied for 7 days. The arm was
      then fully mobilized. Parameters examined were defect location, donor site
      complications, flap survival, fistula occurrence, plate fracture, and/or
      extrusion. RESULTS: Thirty-four patients were reconstructed with the RFOFF with a
      follow-up of 10-54 months. Seven patients had an anterior maxillectomy defect,
      and 27 patients had a lateral mandibulectomy defect with associated
      tongue/tonsillar fossa and/or palate defect. There were no cases of flap failure
      or donor site radius fracture. During the follow-up period, there were no plate
      fractures or intraoral exposures as evidenced by clinical and radiographic
      evaluation. Fistulas occurred in five patients; all healed without surgical
      intervention. CONCLUSION: With rigid fixation of the residual radius, donor site
      morbidity has been minimized, and indications for this flap have expanded.
      Specifically the anterior maxillary arch and the ascending ramus, angle, and
      posterior body of the mandible (nontooth-bearing areas) are the sites most
      amenable to the thin bony stock of the harvested radius. The pliable forearm skin
      is ideal for the soft tissue defects. We believe that the RFOFF with bone has a
      definite role in the reconstruction of select head and neck defects.

PMID- 12784240
TI  - Effect of irradiation on vestibular evoked myogenic potentials in nasopharyngeal
      carcinoma survivors.
AB  - BACKGROUND: This study aims to investigate the effect of irradiation on
      vestibular evoked myogenic potentials (VEMPs) in nasopharyngeal carcinoma (NPC)
      survivors, because radiotherapy to NPC covers a column from the basal skull to
      the clavicle level. METHODS: Twenty-two irradiated NPC survivors and five fresh
      NPC patients were subjected to VEMP testing, which is evoked by short-tone burst
      (95 dBHL, 500 Hz) stimulation. Interactions among VEMPs and radiation effects,
      such as radiation dosage, postirradiation interval, radiation-induced otitis
      media, sensorineural hearing loss, or canal paresis, were then explored. RESULTS:
      The mean latencies of p13 and n23 in irradiated ears were significantly delayed
      compared with either pr-irradiated ears or normal control ears. Delayed VEMPs
      represented 50% in ears with a mean radiation dosage of 71 Gy, whereas it
      represented 100% in those with a mean radiation dosage of 123 Gy. Ears with
      radiation otitis media revealed higher occurrence (65%) of delayed VEMPs than
      those without radiation otitis media (29%, p <.05), possibly because of radiation
      sequela affecting the brainstem and neck. However, delayed VEMPs were unrelated
      to sensorineural hearing loss or canal paresis caused by irradiation.
      CONCLUSIONS: Delayed VEMPs in NPC survivors are possibly due to radiation-induced
      otitis media, a brainstem lesion, or neck fibrosis. Hence, VEMP testing may
      expand the test battery for clinicians to explore balance problems in NPC
      survivors after irradiation.

PMID- 12784241
TI  - Malignant peripheral primitive neuroectodermal tumor-peripheral neuroepithelioma
      of the head and neck: a clinicopathologic study of five cases and review of the
      literature.
AB  - BACKGROUND: The term primitive neuroectodermal tumor (PNET) encompasses a number
      of neoplasms of common neuroectodermal origin, but of variable clinical,
      histopathologic, ultrastructural, and molecular characteristics. Here, we focus
      on one particular member of the PNET family, the malignant peripheral PNET
      (pPNET) or peripheral neuroepithelioma of head and neck. METHODS: Five patients
      diagnosed with malignant pPNET-peripheral neuroepithelioma of head and neck were
      included in the study. All existing literature was reviewed. RESULTS: The
      diagnosis of malignant pPNET-peripheral neuroepithelioma of the head and neck was
      confirmed in all five cases. All patients are alive after treatment with a
      combination of therapeutic modalities; only one patient had metastatic disease
      develop. A literature review revealed another 38 reported cases. CONCLUSIONS:
      Malignant pPNET-peripheral neuroepithelioma should be included in the
      differential diagnosis of small, round, blue cell tumors of head and neck. A
      combination of multiple diagnostic modalities is essential for correct diagnosis,
      and multimodality treatment offers the best outcome.

PMID- 12784242
TI  - Management of unknown primary tumor.

PMID- 12784243
TI  - External auditory canal eccrine spiradenocarcinoma: a case report and review of
      literature.
AB  - BACKGROUND: Eccrine spiradenocarcinoma is a rare dermal appendage carcinoma
      believed to arise from transformation of a long-standing benign spiradenoma. This
      tumor demonstrates highly malignant biologic behavior with a high recurrence
      rate, frequent lymph node metastases, and overall poor survival. METHODS: We
      report the first case of eccrine spiradenocarcinoma arising in the external
      auditory canal. The management of this tumor, its histopathologic
      characteristics, and a review of literature are presented. RESULTS: A literature
      review identified 17 cases of eccrine spiradenocarcinoma in the head and neck
      region. Local recurrence occurred in 58.8% of patients, with an average of 23
      months from diagnosis. Lymph node metastasis occurred in 35.3%, with an average
      of 31 months from diagnosis. Other metastatic sites included skin, bone, and
      lung. Disease-specific mortality was 22.2%. CONCLUSIONS: Eccrine
      spiradenocarcinoma is an aggressive tumor with a poor prognosis. Primary
      treatment should include wide local excision with or without regional
      lymphadenectomy. Isolated successful treatments have been documented with
      adjuvant hormonal manipulation, chemotherapy, and radiation therapy.

PMID- 12784244
TI  - Cloning and expression of cynomolgus monkey and baboon zona pellucida proteins.
AB  - Partial clones for the three cynomolgus monkey (Macaca fasicularis) zona
      pellucida genes (cmZPA, cmZPB, and cmZPC) have previously been isolated. These
      partial clones contained the sequences for the C-terminal portion of each rcmZP
      protein. To obtain full-length clones for each cmZP, a fresh cynomolgus monkey
      ovarian cDNA library was constructed. PCR methodology was employed to speed the
      isolation of full-length clones for each cmZP cDNA. The 3' primers were designed
      based on sequence information from the previously identified clones; the 5'
      primers were designed using the human ZP sequences. The PCR technique yielded
      full-length clones of cmZPA and cmZPC, but not of cmZPB. Therefore, a genomic
      clone of cmZPB was isolated and the sequence determined. The exon/intron
      structure is nearly identical to the human ZPB exon/intron structure. New PCR
      primers were designed based on the cynomolgus monkey ZPB genomic sequence, and a
      full-length cmZPB cDNA was obtained. The same primers that were used to generate
      the cmZPB were also used to generate a baboon (Papio cynocephalus) ZPB (bZPB)
      cDNA. As was done previously for the human zona pellucida (hZP) cDNAs, the cmZP,
      and bZPB cDNAs were transferred to shuttle vectors for transfection into Chinese
      Hamster Ovary (CHO) cells. Stable cell lines for producing each ZP protein were
      isolated. Each cell line secreted the desired recombinant zona pellucida (rZP)
      protein into the culture medium, and each protein was purified using an
      established protocol. In terms of size and purity, the purified recombinant cmZP
      (rcmZP) and rbZPB proteins resemble the rhZP proteins.

PMID- 12784245
TI  - Cell cycle dependent expression of Plk1 in synchronized porcine fetal
      fibroblasts.
AB  - Enzymes of the Polo-like kinase (Plk) family are active in the pathways
      controlling mitosis in several species. We have cloned cDNA fragments of the
      porcine homologues of Plk1, Plk2, and Plk3 employing fetal fibroblasts as source.
      All three partial cDNAs showed high sequence homology with their mouse and human
      counterparts and contained the Polo box, a domain characteristic for all Polo
      kinases. The expression levels of Plk1 mRNA at various points of the cell cycle
      in synchronized porcine fetal fibroblasts were analyzed by both RT-PCR and the
      ribonuclease protection assay. Plk1 mRNA was barely detectable in G0 and G1,
      increased during S phase and peaked after the G2/M transition. A monoclonal
      antibody was generated against an in vitro expressed porcine Plk1-protein
      fragment and used to detect changes in Plk1 expression at the protein level. Plk1
      protein was first detected by immunoblotting at the beginning of S phase and was
      highest after the G2/M transition. In summary, the Plk1 expression pattern in the
      pig is similar to that reported for other species. The absence of Plk1 mRNA and
      protein appears to be a good marker for G0/G1 and thus for the selection of donor
      cells for nuclear transfer based somatic cloning.

PMID- 12784246
TI  - Localization of glutamate cysteine ligase subunit mRNA within the rat ovary and
      relationship to follicular apoptosis.
AB  - Ovarian levels of the antioxidant tripeptide glutathione (GSH) increase following
      gonadotropin administration, suggesting that GSH synthesis in the ovary may be
      associated with follicular growth. In situ hybridization with (35)S-labeled
      riboprobes was used to localize ovarian mRNA expression of the catalytic and
      modulatory subunits of glutamate cysteine ligase (Gclc and Gclm), the rate
      limiting enzyme in GSH synthesis, during each stage of the rat estrous cycle.
      Gclm was highly expressed in the granulosa cells and oocytes of healthy, growing
      follicles, not in atretic follicles. Gclc was also highly expressed in follicles;
      however, unlike Gclm, Gclc was also expressed in corpora lutea and interstitial
      cells. In a subsequent experiment, the hypothesis that GSH synthesis occurs in
      healthy, but not in apoptotic, follicles was tested. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic
      cells in the ovaries, and in situ hybridization for Gclm and Gclc was performed
      in adjacent sections of the same ovaries. TUNEL staining was found to be
      significantly associated with absence of Gclm hybridization in granulosa cells
      and oocytes and with lack of strong Gclc hybridization in granulosa cells. These
      results suggest that follicular apoptosis may be associated with down-regulation
      of Gclm and Gclc transcription in granulosa cells and oocytes.

PMID- 12784247
TI  - In vitro and in vivo effects of a multimerized alphas 1-casein enhancer on whey
      acidic protein gene promoter activity.
AB  - Experimental data obtained in previous works have led to postulate that enhancers
      increase the frequency of action of a linked promoter in a given cell and may
      have some insulating effects. The multimerized rabbit alpha s1-casein gene
      enhancer, the 6i multimer, was added upstream of the rabbit whey acidic protein
      gene (WAP) promoter (-6,300; +28 bp) fused to the firefly luciferase (luc) gene
      (6i WAP-luc construct). The 6i multimer increased reporter gene expression in
      mouse mammary HC11 cells. In transgenic mice, a very weak but significant
      increase was also observed. More noticeable, no silent lines were found when the
      6i multimer was associated to the WAP-luc construct. This reflects the fact that
      the 6i multimer tends to prevent the silencing of the WAP-luc construct. After
      addition of the 5'HS4 insulator region from the chicken beta-globin locus
      upstream of the 6i multimer, similar luciferase levels were measured in 6i WAP
      luc and 5'HS4 WAP-luc transgenic mice. Our present data and previous ones, which
      show that the 6i multimer has no insulating activity on a TK gene promoter
      construct indicate that the insulating activity of the 6i multimer is construct
      dependent and not amplified by the 5'HS4 insulator.

PMID- 12784248
TI  - Successful development of viable blastocysts from enhanced green fluorescent
      protein transgene-microinjected mouse embryos: comparison of culture media.
AB  - To improve efficiency of transgenesis, we compared M16 and CZB embryo culture
      media, supporting development to blastocysts of FVB/N mouse pronuclear-eggs,
      microinjected with enhanced green fluorescent protein (EGFP) transgene. When EGFP
      injected-eggs were cultured (120 hr), blastocyst development was significantly (P
      < 0.03) higher in M16 medium (72.5 +/- 2.4%) than that in CZB (13.2 +/- 4.3%) or
      CZBG (CZB with 5.6 mM glucose at 48 hr culture) (62.1 +/- 3.7%) media. Blastocyst
      development of noninjected embryos was higher in M16 (92.0 +/- 2.6%) and CZBG
      (83.9 +/- 3.9%) media than in CZB (31.9 +/- 2.8%) medium (P < 0.0001). However,
      percentages of morulae at 72 hr were comparable in all treatments. Developed
      blastocysts were better in M16 than in CZB or CZBG media. Consistent with this,
      mean cell number per blastocyst, developed from injected embryos, was
      significantly (P < 0.002) higher in M16 medium (79.6), than those in CZB (31.3)
      or CZBG media (60.7); similar with noninjected embryos. Cell allocation to
      trophectoderm (TE) and inner cell mass (ICM), i.e., TE:ICM ratio, for injected
      blastocysts in M16 (3.0) was less than (P < 0.05) those in CZB (4.2) and CZBG
      (4.4) media; similar with noninjected blastocysts. Moreover, blastocysts,
      developed in M16 and CZBG media, hatched, attached, and exhibited trophoblast
      outgrowth; 18% of them showed EGFP-expression. Importantly, blastocysts from M16
      medium produced live transgenic "green" pups (11%) following embryo transfer.
      Taken together, our results indicate that supplementation of glucose, at 48 hr of
      culture (CZBG), is required for morula to blastocyst transition; M16 medium,
      containing glucose from the beginning of culture, is superior to CZB or CZBG for
      supporting development of biologically viable blastocysts from EGFP-transgene
      injected mouse embryos.

PMID- 12784249
TI  - Asynchronous cytoplast and karyoplast transplantation reveals that the cytoplasm
      determines the developmental fate of the nucleus in mouse oocytes.
AB  - The relationship between nucleus and cytoplasm can be well revealed by nuclear
      transplantation. Here, we have investigated the behavior changes of the
      reconstructed oocytes after transferring the karyoplasts from mouse GV, MI, and
      MII oocytes into the cytoplasts at the different developmental stages. When the
      GV cytoplast was used as recipient and MI or MII karyoplast was used as donor (MI
      GV pair and MII-GV pair), the reconstructed pairs extruded a polar body after
      electrofusion and culture. Both the cytoplasm and the polar body had a metaphase
      spindle in the MI-GV pair, while only a clutch of condensed chromatin was
      observed in the cytoplasm and polar body of the MII-GV pair. When the MI
      cytoplast was used as recipient and GV or MII karyoplast was used as donor (GV-MI
      pair and MII-MI pair), the reconstructed pairs also extruded a polar body. Each
      had one spindle and a group of metaphase chromosomes in the cytoplasm and polar
      body, respectively. When the MII cytoplast was used as recipient and GV or MI
      karyoplast was used as donor (GV-MII pair and MI-MII pair), the reconstructed
      pairs were activated, became parthenogenetic embryos and even developed to
      hatching blastocysts after electrofusion. The result from immunoblotting showed
      that MAP kinase activity was high in the MI and MII cytoplasts, while not
      detected in GV cytoplast. The results demonstrate that the cytoplasmic
      environment determines the behavior of asynchronous donors.

PMID- 12784250
TI  - Expression and role of calcium-ATPase pump and sodium-calcium exchanger in
      differentiated trophoblasts from human term placenta.
AB  - Although placental transfer of maternal calcium (Ca(2+)) is a crucial process for
      fetal development, the biochemical mechanisms are not completely elucidated.
      Especially, mechanisms of syncytiotrophoblast Ca(2+) extrusion into fetal
      circulation remain to be established. In the current study we have investigated
      the characteristics of Ca(2+) efflux in syncytiotrophoblast-like structure
      originating from the differentiation of cultured trophoblasts isolated from human
      term placenta. Time-courses of Ca(2+) uptake by differentiated human trophoblasts
      displayed rapid initial entry (initial velocity (V(i)) of 8.82 +/- 0.86 nmol/mg
      protein/min) and subsequent establishment of a plateau. Ca(2+) efflux studies
      with (45)Ca(2+)-loaded cells also showed rapid decline of cell-associated
      (45)Ca(2+) with a V(i) of efflux (V(ie)) of 8.90 +/- 0.96 nmol/mg protein/min.
      Expression of membrane systems responsible for intracellular Ca(2+) extrusion
      from differentiated human trophoblast were investigated by RT-PCR. Messenger RNAs
      of four known isoforms of PMCA (PMCA 1-4) were detected. Messenger RNAs of two
      cloned human NCX isoforms (NCX1 and NCX3) were also revealed. More specifically,
      both splice variants NCX1.3 and NCX1.4 were amplified by PCR with total RNA of
      differentiated human trophoblast cells. Ca(2+) flux studies in Na-free incubation
      medium indicated that NCX played a minimal role in the cell Ca(2+) fluxes.
      However, erythrosine B (inhibitor of PMCA) time- and dose-dependently increased
      cell associated (45)Ca(2+) suggesting a principal role of plasma membrane Ca(2+)
      ATPase (PMCA) in the intracellular Ca(2+) extrusion of syncytiotrophoblast-like
      structure originating from the differentiation of cultured trophoblast cells
      isolated from human term placenta.

PMID- 12784251
TI  - Cold-induced calcium elevation triggers DNA fragmentation in immature pig
      oocytes.
AB  - Fluo-4 loaded immature oocytes were cooled from 30 degrees C to various lower
      temperatures between 20 and 10 degrees C and changes in intracellular calcium
      (Ca(2+)) levels were measured. Pig oocytes cooled to 14 degrees C exhibited a
      clear biphasic Ca(2+) rise. Lower temperatures produced similar responses, while
      higher temperatures did not exert any effect. The Ca(2+) response appeared to
      rely on ryanodine dependent stores as removal of extracellular Ca(2+) and
      intracytoplasmic injection of heparin did not modify cold-induced Ca(2+)
      elevation, while procaine or ruthenium red virtually eliminated the response.
      Confocal analysis of subcellular Ca(2+) distribution during cooling revealed that
      the ion rises sharply within the nucleus. As Ca(2+) imbalance may activate
      nuclear endonucleases, DNA integrity of cooled pig oocytes was evaluated by TUNEL
      and comet assays. Most cooled oocytes showed clear signs of DNA fragmentation.
      Oocytes injected with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid
      tetrapotassium salt (BAPTA), a Ca(2+) chelator, maintained their DNA integrity
      thus confirming that intracellular Ca(2+) is involved in triggering DNA
      fragmentation. The protective effect exerted by ruthenium red and/or procaine
      further confirmed this hypothesis. These data show that a moderate and transient
      cooling is sufficient to cause an intracellular Ca(2+) rise that leads to DNA
      damage. The addition of inhibitors of ryanodine dependent Ca(2+) stores may
      represent a valuable protective treatment to reduce chilling injuries.

PMID- 12784252
TI  - Spermatid nuclear and sperm periaxonemal anomalies in the mouse Ube2b null
      mutant.
AB  - Ube2b (yeast Ubc2b/Rad6 homolog) null mice were described previously. Ube2b
      encodes the murine ubiquitin conjugating enzyme mHR6B. Ube2b(-/-) mice were shown
      to present male infertility and their sperm head shape anomalies suggested that
      Ube2b may be involved in the replacement of nuclear proteins during spermatid
      chromatin condensation. Apoptosis of spermatocytes suggested additional targets
      of Ube2b during spermatogenesis. Consistently, we found Ube2b transcription in
      both meiotic and postmeiotic stages by in situ hybridization. Immuno-electron
      microscopy revealed that transition proteins 1 and 2, protamines 1 and 2, and
      actin appear normally distributed during morphogenesis of Ube2b(-/-) spermatid
      heads. Surprisingly, electron microscopy revealed a particular sperm flagellum
      phenotype characterized by an abnormal distribution of periaxonemal structures.
      Flagellar anomalies of Ube2b null mice were previously described in infertile men
      indicating a possible genetic pathway for flagellar periaxonemal assembly in
      human.

PMID- 12784253
TI  - Efficacy of antibodies against Escherichia coli expressed chimeric recombinant
      protein encompassing multiple epitopes of zona pellucida glycoproteins to inhibit
      in vitro human sperm-egg binding.
AB  - To minimize ovarian dysfunction subsequent to immunization with zona pellucida
      (ZP) glycoproteins, synthetic peptides encompassing the antigenic B cell epitopes
      as immunogens have been proposed. In this study, attempts have been made to clone
      and express a recombinant chimeric protein encompassing the epitopes
      corresponding to bonnet monkey (Macaca radiata) ZP glycoprotein-1 (bmZP1, amino
      acid residues 132-147), ZP glycoprotein-2 (bmZP2, amino acid residues 86-113),
      and ZP glycoprotein-3 (bmZP3, amino acid residues 324-347). The above chimeric
      recombinant protein (r-bmZP123) was expressed as a polyhistidine fusion protein
      in Escherichia coli. Immunoblot with murine monoclonal antibody, MA-813,
      generated against recombinant bmZP1 revealed a major band of approximately 10
      kDa. The r-bmZP123 was purified on nickel-nitrilotriacetic acid resin under
      denaturing conditions. The female rabbits immunized with purified r-bmZP123
      conjugated to diphtheria toxoid (DT) generated antibodies that reacted with r
      bmZP123 and DT in an ELISA. In addition, the immune sera also reacted with E.
      coli expressed recombinant bmZP1, bmZP2, and bmZP3. In an indirect
      immunofluorescence assay, the antibodies against r-bmZP123 recognized native ZP
      of bonnet monkey as well as human. The immune sera also inhibited, in vitro, the
      binding of human spermatozoa to the human zona in the hemizona assay (HZA). These
      studies, for the first time, demonstrate the feasibility of assembling multiple
      epitopes of different ZP glycoproteins as a recombinant protein that elicit
      antibodies which are reactive with native zona and also inhibit, in vitro, human
      sperm-oocyte binding.

PMID- 12784254
TI  - Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies
      its functional roles in the regulation of meiotic maturation, fertilization, and
      cleavage.
AB  - Polo-like kinase 1 (Plk1) is a family of serine/threonine protein kinases that
      play important regulatory roles during mitotic cell cycle progression. In this
      study, Plk1 expression, subcellular localization, and possible functions during
      rat oocyte meiotic maturation, fertilization, and embryonic cleavages were
      studied by using RT-PCR, Western blot, confocal microscopy, drug-treatments, and
      antibody microinjection. Both the mRNA and protein of this kinase were detected
      in rat maturing oocytes and developing embryos. Confocal microscopy revealed that
      Plk1 distributed abundantly in the nucleus at the germinal vesicle (GV) stage,
      was associated with spindle poles during the formation of M-phase spindle, and
      was translocated to the spindle mid-zone at anaphase. In fertilized eggs, Plk1
      was strongly stained in the cytoplasm between the apposing male and female
      pronuclei, from where microtubules radiated. Throughout cytokinesis, Plk1 was
      localized to the division plane, both during oocyte meiosis and embryonic
      mitosis. The specific subcellular distribution of Plk1 was distorted after
      disrupting the M-phase spindle, while additional aggregation dots could be
      induced in the cytoplasm by taxol, suggesting its intimate association with
      active microtubule assembly. Plk1 antibody microinjection delayed the meiotic
      resumption and blocked the emission of polar bodies. In conclusion, Plk1 may be a
      multifunctional kinase that plays pivotal regulatory roles in microtubule
      assembly during rat oocyte meiotic maturation, fertilization, and early embryonic
      mitosis.

PMID- 12784255
TI  - Prolin-rich tyrosine kinase 2 (PYK2) expression and localization in mouse testis.
AB  - Prolin-rich kinase 2 (PYK2) is a nonreceptor tyrosine kinase related to the focal
      adhesion kinase (FAK) p125(FAK). PYK2 is rapidly phosphorylated on tyrosine
      residues in response to various stimuli, such as tumor necrosis factor-alpha (TNF
      alpha), changes in osmolarity, elevation in intracellular calcium concentration,
      angiotensin, and UV irradiation. PYK2 has ligand sequences for Src homology 2 and
      3 (SH-2 and SH-3), and has binding sites for paxillin and p130(cas). Activation
      of PYK2 leads to modulation of ion channel function, phosphorylation of tyrosine
      residues, and activation of the MAP kinase signaling pathways.
      Immunocytochemistry shows that PYK2 is present in mouse germinal and Sertoli
      cells (ser). Northern blot and immunoprecipitation analysis demonstrate that,
      among germinal cells, PYK2 is more abundant in spermatocytes (spc) and spermatids
      (spt); in addition, immunofluorescence analysis clearly shows that the diffuse
      cytoplasmic localization of PYK2 changes in a specific cellular compartment in
      spt and spermatozoa.

PMID- 12784256
TI  - Meiotic state of bovine oocytes is regulated by interactions between cAMP,
      cumulus, and granulosa.
AB  - Bovine oocytes are arrested at the prophase of first meiotic cell cycle. Meiosis
      resumes in oocytes of pre-ovulatory follicles upon LH surge. However, oocytes
      from secondary follicles spontaneously resume meiosis in the absence of hormones
      if removed from the follicle and cultured in vitro. The nature of meiotic
      arrestor in bovine follicles is poorly understood. In this study we investigated
      the role of cell-cell interactions between granulosa and cumulus cells and the
      oocyte in mediating maintenance of meiotic arrest by cAMP. We sorted oocytes as
      granulosa-cumulus oocyte complexes (GCOC) if surrounded with cumulus cells
      attached to a large granulosa investment or cumulus oocytes complexes (COC) if
      surrounded with cumulus cells only and investigated the role cAMP in maintenance
      of meiotic arrest in these oocytes under various conditions. In hormone- and
      serum-free medium both GCOC and COC enclosed oocytes resumed meiosis. When
      [cAMP](i) was elevated with addition of invasive adenylate cyclase (iAC) GCOC
      enclosed oocytes were maintained in the prophase with intact germinal vesicle
      (GV) while COC enclosed oocytes underwent GV breakdown (GVBD). iAC elevated
      [cAMP](i) in both types of oocytes to the same level. If oocytes were liberated
      from the cumulus and granulosa cells, they re-initiated meiosis in serum and
      hormone free medium, but remained in the GV stage if iAC was added to the medium.
      Untreated GCOC and COC enclosed oocytes extruded first polar body at the same
      frequency in hormone-supplemented media. GCOC and COC enclosed oocytes but not
      denuded oocytes (DO) cultured without somatic cells acquired developmental
      competence if cultured in hormone-containing medium. It is concluded that
      maintenance of meiotic arrest is regulated by the interplay of [cAMP](i), and
      cumulus and granulosa cells.

PMID- 12784257
TI  - Cell-free DNA is released from tumor cells upon cell death: a study of tissue
      cultures of tumor cell lines.
AB  - To determine the source of cell-free DNA detected in the serum of cancer
      patients, we monitored the release of cell-free DNA and tumor markers from tumor
      cell lines using the cell culture technique. During the first 6 days of cell
      culture, we found very low concentrations of DNA and a steady increase of the CA
      125 released from the SK-BR3 tumor cell lines during cell growth. A sudden
      increase of cell-free DNA detected in the cell medium coincided with cell death.
      As the cells died, the concentration of cell-free DNA declined but the
      concentration of CA 125 increased. The sudden release of cell-free DNA observed
      upon cell death was also found on the cell cultures of additional tumor cell
      lines, including A549, RD, and SK-N-SH cells. It appears that the majority of
      cell-free DNA detected in the serum of cancer patients comes from tumor cells
      following cell death and cell necrosis. The concentration of cell-free DNA
      released is related to the number of dead cells, whereas that of the tumor marker
      CA 125 is associated with the presence of the total number of cells (dead or
      alive).

PMID- 12784258
TI  - Multiplex PCR: rapid DNA cycling in a conventional thermal cycler.
AB  - Multiplex polymerase chain reaction (PCR) is a variant of PCR in which two or
      more target sequences are simultaneously amplified in the same reaction. In the
      present study we investigated the limits to which the duration of multiplex PCR
      steps can be shortened using the thermal cycler Gene Amp PCR system 9600 (Perkin
      Elmer, Oak Brook, IL). The present multiplex PCR assay simultaneously detects
      five different herpes viruses (HSV-1, HSV-2, VZV, CMV, and EBV) and assesses
      sample suitability in a single amplification round of 40 cycles. It appears that
      when six target sequences are simultaneously amplified in multiplex PCR,
      extension time is a critical parameter. Using a PCR protocol of 0 sec at 95
      degrees C, 0 sec at 60 degrees C, and 0 sec at 74 degrees C with Platinum Taq DNA
      polymerase (Life Technologies, Gaithersburg, MD), we were able to reduce the
      total cycling time of the multiplex PCR assay to as little as 55 min, without
      affecting the yield of PCR products or the specificity of the assay. It may be
      necessary to optimize each specific apparatus and template, but any such
      optimization would be trivial.

PMID- 12784259
TI  - Evaluation of the Sysmex Xe-2100 hematology analyzer in hospital use.
AB  - The Sysmex XE-2100 (Sysmex Corp. Kobe, Japan) is a latest-generation hematology
      analyzer. Its optical and electrical measuring technology is improved by the
      addition of flux cytometry, fluorescence, and differential lysis. Its analytical
      performance in terms of precision, reproducibility, linearity, carryover, and
      time stability was found to be entirely satisfactory. In addition, the results of
      500 complete blood counts and differentials correlated perfectly with those
      obtained by the Coulter STKS (Beckman Coulter, Villapointe, France). The
      comparison of 500 leukocyte differential count results analyzed in parallel with
      optical microscopy and the XE-2100 were surprising, and favorable to the XE-2100.
      This analyzer provides the user with an undeniable feeling of security concerning
      its reliability in detecting and identifying anomalies in the automated leukocyte
      differential count. With a sensitivity of 96%, a negative predictive value (NPV)
      of 98%, and a false-negative (FN) rate of 4%, the XE-2100 has perhaps reached the
      technological limits for a machine performing morphological recognition of normal
      and pathological blood cells.

PMID- 12784260
TI  - Comparative study of total protein, and total and lipid-associated serum sialic
      acid levels in patients with type 2 diabetes mellitus.
AB  - The aim of the present study was to investigate the serum total protein (TP),
      total sialic acid (TSA), lipid-associated sialic acid (LSA), LSA/TP, and LSA/TP
      values in type 2 diabetes mellitus (DM) patients. Two study groups (healthy
      controls and type 2 DM subjects) were examined. For the type 2 DM group, 120
      patients (60 females and 60 males) who had been diagnosed and treated for type 2
      DM in the Yuzuncu Yil University Hospital, Van, Turkey, were selected
      consecutively. Forty healthy individuals (20 females and 20 males) were selected
      from hospital staff and other outpatient clinics to serve as the control group.
      They were matched for age, sex, body mass index, and smoking status. None of the
      participants had taken vitamin or mineral supplements for at least 2 weeks before
      sampling. To determine serum glucose, TP, TSA, and LSA levels, blood samples were
      drawn after all of the subjects fasted overnight. It was found that diabetics had
      higher TSA, LSA, TSA/TP, and LSA/TP levels than controls. However, the TP levels
      were not significantly different between the groups. Our results showed that TSA,
      LSA, TSA/TP, and LSA/TP have interactive connections with DM. These parameters
      can be used as a diagnostic index for patients with DM.

PMID- 12784261
TI  - Analysis of urinary N-acetyl-beta-D-glucosaminidase using 2,4-dinitrophenyl-1
      thio N-acetyl-beta-D-glucosaminide as the substrate.
AB  - 2,4-Dinitrophenyl-1-thio N-acetyl-beta-D-glucosaminide was examined as a new
      substrate for analyzing the level of N-acetyl-beta-D-glucosaminidase in the urine
      of patients suffering from renal diseases. The analysis is based on the fact that
      the substrate, when hydrolyzed in the presence of N-acetyl-beta-D
      glucosaminidase, liberates 2,4-dinitrothiophenol as the chromogen. The optimum pH
      for the enzyme reaction is 4.6, which is covered by the optimal range for the UV
      absorbance of the chromogen. The first-order rate of increase of the absorbance
      at this pH was linear to the enzyme concentration up to 600 U/L, with a high
      sensitivity. Analytical reagents with glucosaminides of 2,4-dinitrophenol and 2
      chloro-4-nitrophenol are less stable than the reagent with glucosaminide of 2,4
      dinitrothiophenol. The optimum pH for the absorbance of p-nitrophenol and 2
      chloro-4-nitrophenol does not match that for the enzyme reaction.

PMID- 12784262
TI  - Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera
      fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling
      ciguatoxin, as assessed with MAb-CTX.
AB  - Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic
      ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology.
      These similarities in the literature suggested the exploration of lipids in sera
      of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which
      is typically used for screening ciguateric ocean fish. Sera from patients with
      other diseases, including hepatitis B, cancer, and diabetes, were included to
      assess the degree of specificity involved. Sera were treated with acetone in a
      ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the
      acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL
      methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted
      acetone fraction of the 37 normal showed +/- activity to +activity with 16 no
      titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40
      titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in
      the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer,
      50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or
      =1:40 titer. Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP
      samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These
      data are summarized in Fig. 1. As shown in Table 1, a significant increase
      (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal
      group. A preliminary chemical study in C18 octadecylsilyl columns showed all
      fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol,
      and 100% methanol) to contain lipids reactive to MAb-CTX with different
      intensities. Prostaglandins were shown in 100% methanol fraction. Competitive MIA
      with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope
      suggested similarities in structure with ciguatoxin. This was compatible with the
      neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1,
      chloroform : methanol solvents.

PMID- 12784263
TI  - Role of the somatosensory system in primary dystonia.
AB  - The pathophysiology of dystonia is still not fully understood, but it is widely
      held that a dysfunction of the corticostriatal-thalamocortical motor circuits
      plays a major role in the pathophysiology of this syndrome. Although the most
      dramatic symptoms in dystonia seem to be motor in nature, marked somatosensory
      perceptual deficits are also present in this disease. In addition, several lines
      of evidence, including neurophysiological, neuroimaging and experimental
      findings, suggest that both motor and somatosensory functions may be defective in
      dystonia. Consequently, abnormal processing of the somatosensory input in the
      central nervous system may lead to inefficient sensorimotor integration, thus
      contributing substantially to the generation of dystonic movements. Whether
      somatosensory abnormalities are capable of triggering dystonia is an issue
      warranting further study. Although it seems unlikely that abnormal somatosensory
      input is the only drive to dystonia, it might be more correlated to the
      development of focal hand than generalized dystonia because local somesthetic
      factors are more selectively involved in the former than in the latter where,
      instead it seems to be a widespread deficit in processing sensory stimuli of
      different modality. Because basal ganglia and motor areas are heavily connected
      not only with somatosensory areas, but also with visual and acoustic areas, it is
      possible that abnormalities of other sensory modalities, such as visual and
      acoustic, may also be implicated in the pathophysiology of more severe forms of
      primary dystonia. Further studies have to be addressed to the assessment of the
      role of sensory modalities and their interaction on the pathophysiology of
      different forms of primary dystonia.

PMID- 12784264
TI  - Neuropsychiatric interpretations of postencephalitic movement disorders.
AB  - This study reviews the impact of encephalitis lethargica (EL) on concepts of
      behaviour and movement during the 1920s and 1930s. Clinicopathological
      correlations were imprecise but supported the role of subcortical structures in
      complex patterns of motor behaviour. This possibility challenged the widely
      assumed hegemony of the cerebral cortex. There was a perceived link between
      involuntary movements and reduced impulse control and also between parkinsonism
      and a defect in volition. Contemporary observers interpreted postencephalitic
      phenomena such as oculogyria in psychodynamic as well as in neurophysiological
      terms. EL also gave some support to the idea that neuroses such as obsessional
      neurosis and hysteria might have an organic basis. These speculations recently
      have acquired more credibility. The large amount of literature on EL and its
      sequelae could perhaps make further contributions to understanding the pathology
      of voluntary movement and action.

PMID- 12784266
TI  - Development and testing of the Parkinson's disease quality of life scale.
AB  - We report on the development and results of preliminary psychometric testing of a
      disease specific health-related quality of life (HRQoL) scale intended for use in
      individuals diagnosed with idiopathic Parkinson's disease (PD). Results from an
      initial qualitative study provided content for item development and scale
      construction of the Parkinson's disease quality of life scale (PDQUALIF). The 33
      item instrument includes seven domains: social/role function, self
      image/sexuality, sleep, outlook, physical function, independence, and urinary
      function, plus one item of Global HRQoL. Initial psychometric testing of the
      instrument was conducted in 233 outpatient clinic attendees with physician
      confirmed idiopathic PD. Factor structure, reliability and validity of the scale
      have been established in this cross-sectional study. Continuing development of
      the PDQUALIF will be directed at enhancing the psychometric properties,
      establishing responsiveness and determining appropriateness in culturally diverse
      samples.

PMID- 12784265
TI  - Complex interactions in Parkinson's disease: a two-phased approach.
AB  - The identification of pathogenic mutations in the three genes alpha-synuclein,
      parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the
      ubiquitin proteasome system (UPS) and its potential role as a causal pathway in
      Parkinson's disease (PD). In addition, polymorphisms of these three genes have
      been shown to be independently associated with PD. In a sample of 298 unrelated
      PD cases and 185 controls, we applied a two-phased approach of recursive
      partitioning and logistic regression analyses to explore complex interactions.
      For women only, we observed an epistatic interaction of UCHL1 and alpha-synuclein
      genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our
      findings are consistent with the hypothesis that PD is a multigenic disorder of
      the UPS.

PMID- 12784267
TI  - Prospective study of phobic anxiety and risk of Parkinson's disease.
AB  - Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD
      among people with anxiety has not been examined in a prospective cohort study. We
      examined this relation prospectively within the Health Professionals Follow-Up
      Study, a cohort of US male health professionals. In 1988, anxiety was assessed
      using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or
      cancer at baseline. There were 189 incident cases of PD during 12 years of follow
      up. After adjusting for age, smoking, and caffeine intake, the relative risk of
      PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and
      above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest
      level of anxiety. This positive association persisted after excluding cases of PD
      with onset in the first 2 years of follow-up. Use of anxiolytic medication was
      also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but
      adjusting for this potential confounder did not materially affect the association
      between anxiety and risk of PD. Our results suggest that anxiety is a risk factor
      for PD. Whether this association is causal or the result of shared underlying
      biology remains a question.

PMID- 12784268
TI  - Effect of cognitive and motor tasks on postural stability in Parkinson's disease:
      a posturographic study.
AB  - To analyse the effect of concomitant cognitive or motor task performance on
      balance control in Parkinson's disease (PD), we performed a posturographic study
      in 24 PD patients and in 20 sex- and age-matched control subjects. Postural sway
      was measured with eyes open (EO) and eyes closed (EC) during quiet stance and
      during performance of calculation or motor sequence of thumb opposition to the
      other fingers. No difference of centre of foot pressure (COP) parameters was
      observed during quiet standing (either EO or EC) between patients and controls,
      but visual deprivation induced in both groups a worsening of postural stability.
      COP area was significantly increased in PD patients during dual task performance,
      whereas no difference of COP path and x-y axes was observed. The effects induced
      by the performance of cognitive or motor task were significantly more evident in
      PD patients with clinical evidence of postural instability (presence of prior
      falls in the history). This study demonstrates that dual task interference on
      postural control can be observed in PD patients during performance of cognitive
      as well as motor tasks. The balance deterioration during dual task performance
      was significantly enhanced in patients with history of prior falls. These
      findings have some implications for the strategies to be used in reducing the
      risk of fall in PD.

PMID- 12784269
TI  - Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease.
AB  - To study the putative association of dopamine agonists with sleep attacks in
      patients with Parkinson's disease (PD) and their relation to daytime sleepiness,
      we performed a survey of 2,952 PD patients in two German counties. In 177
      patients, sudden, unexpected, and irresistible sleep episodes while engaged in
      some activity were identified in a structured telephone interview. Ninety-one of
      these patients denied the occurrence of appropriate warning signs. A total of 133
      patients (75%) had an Epworth Sleepiness Scale (ESS) score >10; 65 (37%) >15.
      Thirty-one patients (18%) had an ESS score < or =10 and yet experienced sleep
      attacks without warning signs. Thus, although a significant proportion of
      patients at risk for sleep attacks might be identified using the ESS, roughly 1%
      of the PD patient population seems to be at risk for sleep attacks without
      appropriate warning signs and without accompanying daytime sleepiness. Sleep
      attacks occurred with all dopamine agonists marketed in Germany (alpha
      dihydroergocryptine, bromocriptine, cabergoline, lisuride, pergolide,
      pramipexole, ropinirole), and no significant difference between ergot and
      nonergot drugs was evident. Levodopa (L-dopa) monotherapy carried the lowest risk
      for sleep attacks (2.9%; 95% confidence interval [CI], 1.7-4.0%) followed by
      dopamine agonist monotherapy (5.3%; 95% CI, 1.5-9.2%) and combination of L-dopa
      and a dopamine agonist (7.3%; 95% CI, 6.1-8.5%). Neither selegeline nor
      amantadine or entacapone appeared to influence the occurrence of sleep attacks. A
      high ESS score, intake of dopamine agonists, and duration of PD were the main
      influencing factors for the occurrence of sleep attacks. The odds ratio for
      dopamine agonist therapy was 2.9 compared to 1.9 with L-dopa therapy and 1.05 for
      a 1-year-longer disease duration.

PMID- 12784270
TI  - Sleepiness in Parkinson's disease: a controlled study.
AB  - Sudden-onset sleep episodes while driving have been reported in Parkinson's
      disease (PD) patients, and termed sleep attacks because they were reported to be
      irresistible and to occur without warning. We postulate that these episodes are
      due to excessive daytime sleepiness secondary to the high frequency of sleep
      disorders in PD patients and the sedative effects of dopaminergic medications. We
      assessed the frequency and relationship between excess daytime sleepiness and
      sleep episodes while driving (SE) in patients with PD. We evaluated 101
      consecutive PD patients presenting to the Movement Disorder Center at the Mount
      Sinai School of Medicine using a questionnaire that incorporated a subjective
      estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on
      disease severity and dopaminergic medications. One hundred age-matched
      respondents without PD served as a control population. Excess daytime sleepiness
      was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The
      mean ESS scores for PD patients was 9.1 +/- 6.1 versus 5.7 +/- 4.4 in controls (P
      < 0.001). ESS scores > or =10 were observed in 40.6% of PD patients compared to
      19% of controls (P < 0.01) and 24% of PD patients had scores > or =15, compared
      to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by
      20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily
      levodopa (L-dopa) dose equivalent was 1,142 +/- 858 mg in PD drivers who
      experienced a SE while driving compared to 626 +/- 667 mg in those who had not (P
      < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in
      those without (11.6 +/- 6.4 vs. 8.4 +/- 4.1; P < 0.05). Logistic regression
      analysis demonstrated that ESS and mean daily L-dopa dose equivalents were
      predictors of sleep episodes while driving, whereas age, gender, disease
      severity, and individual dopaminergic agents were not. These findings support the
      notion that sleep episodes while driving in PD patients are related to excess
      daytime sleepiness and dopaminergic load. Physicians should advise and treat
      patients accordingly.

PMID- 12784271
TI  - Abnormal cortical sensory activation in dystonia: an fMRI study.
AB  - Despite the obvious motor manifestations of focal dystonia, it is recognised that
      the sensory system plays an important role in this condition. This functional
      magnetic resonance imaging study examines the sensory representations of
      individual digits both within the subregions of the primary sensory cortex (SI)
      and in other nonprimary sensory areas. Patients with focal dystonia and controls
      were scanned during vibrotactile stimulation of both the index (digit 2) and
      little (digit 5) fingers of their dominant hand (which was the affected hand in
      all the dystonic subjects). The activation maps obtained were analysed for
      location, size, and magnitude of activation and three-dimensional (3-D)
      orientation of digit representations. Data from both groups were compared. There
      were significant differences in the average 3-D separation between the two digit
      representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for
      controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends
      for reversed ordering of the representation of the two digits in both the
      secondary sensory cortex and posterior parietal area between the two groups. In
      addition, in dystonic subjects, there was significant under activation in the
      secondary somatosensory cortex (SII/area 40) for both digits and in the posterior
      parietal area for digit 5. These results indicate the presence of widespread
      activation abnormalities in the cortical sensory system in dystonia.

PMID- 12784272
TI  - Flumazenil, a GABA antagonist, may improve features of Parkinson's disease.
AB  - Manipulation of gamma-aminobutyrate (GABA) system has been little studied in
      Parkinson's disease, despite the fact that GABA subserves a large part of the
      basal ganglia, including the outflow tracts. To test whether antagonism of GABA
      could improve features of PD, we administered open label intravenous flumazenil
      to eight practically defined off patients and assessed UPDRS scores, bilateral 1
      minute hand-tapping speed, and timed gait tests. Patients demonstrated
      significantly greater tapping speed, which peaked 40 minutes after injection (P <
      0.05). Total motor Unified Parkinson's Disease Rating Scale scores modestly
      improved (P < 0.05). There were no adverse events. Mechanisms by which flumazenil
      could improve PD are discussed.

PMID- 12784273
TI  - Double-blind, placebo-controlled study to evaluate the efficacy and safety of
      botulinum toxin type A in the treatment of drooling in parkinsonism.
AB  - Drooling is a frequent symptom in Parkinson's disease (PD), occurring in almost
      75% of all patients. Although it is now well known that drooling in PD is the
      result of swallowing difficulties rather than excessive saliva production, few
      treatments have been developed to reduce it. Clinical studies suggest that
      botulinum toxin A (BTX) injections into salivary glands are effective in
      decreasing drooling in PD patients. In this double-blind, placebo-controlled
      study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy),
      were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or
      2 ml of placebo, injected into the parotids and submandibular glands under
      ultrasonographic guidance. Treatment efficacy and safety were assessed at
      baseline, 1 week and 3 months after BTX injections using clinical scales
      (Drooling Severity and Drooling Frequency scales) and side effects surveillance.
      After treatment, the average secretion of saliva in the BTX group was
      significantly lower than in the placebo group, as appraised by clinical
      measurements. No side effects were observed in either group. BTX injection into
      parotids and submandibular glands, under ultrasonographic guidance, is an
      effective and safe treatment for drooling in parkinsonism.

PMID- 12784274
TI  - Does ageing have an effect on midbrain premotor nuclei for vertical eye
      movements?
AB  - Currently, there is debate in the clinical literature as to whether defects in
      vertical gaze are a consequence of normal ageing or a component of an underlying
      neurodegenerative disorder. Although pathological changes have been demonstrated
      in diseased subjects, no study to date has addressed the question of normal
      ageing effects. In this retrospective study, we examined 23 neurologically and
      pathologically normal subjects (age 18-91). Using an unbiased, frame-based
      sampling method, we quantified neuronal and glial cell densities in 10 young
      (<50) and 13 aged (>65) subjects in the rostral interstitial nucleus of the
      medial longitudinal fasciculus (riMLF), the key premotor substrate in the
      vertical gaze pathway. We found no statistically significant difference in
      neuronal density, glial cell density, or neuron-to-glial cell ratios between the
      young and the aged. We conclude, therefore, that neuronal loss, neuronal atrophy,
      or gliosis in the riMLF are not consequences of normal ageing.

PMID- 12784275
TI  - Lack of association between progressive supranuclear palsy and arterial
      hypertension: a clinicopathological study.
AB  - It has been reported that up to 80% of patients clinically diagnosed as having
      progressive supranuclear palsy (PSP) may have arterial hypertension (HT). Because
      previous studies were performed on patients with presumed diagnosis of PSP, we
      tried to replicate these studies in a series of pathologically confirmed
      patients. Seventy-three patients with a neuropathological diagnosis of PSP
      autopsied at the Queen Square Brain Bank for Neurological Disorders in London
      were collected between 1989 and 1999. For the purpose of this study, patients
      were considered hypertensive if a blood pressure above 140/90 mm Hg was found in
      the clinical records. The prevalence of HT in PSP patients at the first and at
      the last visit during their neurological disease was compared with that found in
      a series of 21 normal controls who donated their brain to the same institution.
      Overall, 29 of 73 (39.7%) of the patients were recorded as having HT at the first
      visit during the disease course; this ratio increased to 42 of 73 (57.5%) at the
      last visit before death. When these figures were compared to the 21 normal
      controls (11 of 21 with HT, 52.4%), we were unable to find an increased
      prevalence of HT in PSP (odds ratio, 0.60; 95% confidence interval, 0.20-1.76).
      Therefore, HT does not represent an important clinical feature of this
      neurodegenerative disorder, although cerebrovascular disease can masquerade
      clinically as PSP.

PMID- 12784276
TI  - Brain perfusion SPECT in patients with corticobasal degeneration: analysis using
      statistical parametric mapping.
AB  - We sought to determine the characteristics of brain perfusion in patients with
      corticobasal degeneration (CBD) using single photon emission computed tomography
      (SPECT) and statistical parametric mapping (SPM). Thirteen patients with CBD and
      10 age-matched healthy volunteers were examined using brain perfusion SPECT and
      (99m)Tc-ethyl cysteinate dimer (ECD). Regional cerebral blood flow (rCBF)
      measurements were performed noninvasively using a graphic analysis method. Both
      the absolute rCBF data (raw data) and the adjusted rCBF data (global CBF
      normalized to 50 ml/100 g/min) were used in the SPM analysis. A significant
      decrease in the absolute rCBF was observed in extended areas of the brain in CBD
      patients compared to the control group. These areas included the frontal,
      parietal, and temporal cortices; basal ganglia; thalamus; and pontocerebellar
      regions. Our results suggest that the extent of the reduced rCBF region in CBD
      patients is more widespread than previously reported.

PMID- 12784277
TI  - Tetrabenazine in the treatment of severe pediatric chorea.
AB  - Tetrabenazine (TBZ) is widely used to treat adults with hyperkinetic movement
      disorders; however, published experience with the drug in pediatric patients is
      limited. We report on 5 children with severe chorea who were treated with TBZ.
      TBZ effectively controlled chorea in 4 patients, and despite the need for
      relatively high doses, it was well tolerated.

PMID- 12784278
TI  - Unusual phenotypes in DYT1 dystonia: a report of five cases and a review of the
      literature.
AB  - Since the advent of widespread testing for the presence of the DYT1 gene
      mutation, the range of phenotypes that have been associated with this genetic
      abnormality has expanded. We report on 5 DYT1 gene-positive patients with unusual
      phenotypes. Two of them had late presentation, one of these after peripheral
      injury. Three additional patients had late progression of symptoms, onset after
      exposure to haloperidol, and severe bulbar involvement, respectively. The
      clinical heterogeneity of this condition raises problems for clinicians in
      selecting appropriate patients for diagnostic testing. Also, because of the low
      phenotypic penetrance of DYT1 dystonia, the discovery of the DYT1 mutation in a
      patient with an atypical clinical syndrome may not necessarily suggest a causal
      relationship. We have, therefore, analysed all published clinical studies of DYT1
      dystonia to guide clinical decision making concerning DYT1 gene testing based on
      current information.

PMID- 12784279
TI  - Akathisia as a side effect of antipsychotic treatment with quetiapine in a
      patient with Parkinson's disease.
AB  - Due to its low profile for extrapyramidal side-effects, quetiapine has become an
      alternative to clozapine in the treatment of dopamimetic psychosis in patients
      with Parkinson's disease (PD). We describe the case of a patient with PD who
      developed severe akathisia, a common complication with classical antipsychotics,
      with quetiapine.

PMID- 12784280
TI  - Unilateral subthalamic deep brain stimulation in advanced Parkinson's disease.
AB  - Eight patients with advanced PD received a unilateral STN DBS. The UPDRS III off
      drug-on DBS was improved by a mean 44%. Dyskinesias were ameliorated. Levodopa
      daily dose was reduced. Three patients required the implantation of the second
      electrode. Unilateral DBS may be efficacious in some patients with advanced PD.

PMID- 12784281
TI  - Spasmodic dysphonia in a patient with the A to G transition at nucleotide 8344 in
      mitochondrial DNA.
AB  - Dystonia has been described in various diseases affecting mitochondrial function
      but spasmodic dysphonia, a form of focal dystonia, has not. We present a patient
      with action myoclonus affecting the hands and arms who carried the most common
      mutation in mitochondrial DNA causing the myoclonic epilepsy and ragged red
      fibers (MERRF) syndrome (the A-->G substitution at nucleotide 8344 in the
      tRNA(Lys) gene). This patient also had spasmodic dysphonia that was responsive to
      treatment with intralaryngeal botulinum toxin.

PMID- 12784282
TI  - Painless legs and moving toes in a mother and her daughter.
AB  - Painful legs and moving toes (PLMT) is a rare syndrome which is characterised by
      involuntary movements of the toes and pain in the legs. We report on a mother and
      her daughter who both presented with involuntary movements of the toes similar to
      those seen in PLMT but without any associated pain. Neurological examination
      revealed intermittent 0.3 to 0.5-Hz flexion and extension of the toes and ankles
      of the right foot in the mother, and of both feet in the daughter. In both
      patients, the movements appeared during periods of rest that were uncorrelated
      with the time of day. Diagnostic work-up gave no evidence of radiculopathy or of
      focal neuropathy. Overnight polysomnography documented that movements of the toes
      and feet occurred only before sleep onset and during periods of nocturnal
      awakening or arousals. Because the movements observed in our patients were
      similar to those seen in patients with PLMT, we diagnosed an abortive form of
      this syndrome, which already has got the naming "painless legs and moving toes."
      The occurrence in a mother and her daughter may point to a hereditary component
      of this disorder.

PMID- 12784283
TI  - Prevalence of stroke in Parkinson's disease.

PMID- 12784284
TI  - Occlusal relief changes with molar wear in Pan troglodytes troglodytes and
      Gorilla gorilla gorilla.
AB  - Most research on primate tooth form-function relationships has focused on unworn
      teeth. This study presents a morphological comparison of variably worn lower
      second molars (M(2)s) of lowland gorillas (Gorilla gorilla gorilla; n=47) and
      common chimpanzees (Pan troglodytes troglodytes; n=54) using dental topographic
      analysis. High-resolution replicas of occlusal surfaces were prepared and scanned
      in 3D by laser scanning. The resulting elevation data were used to create a
      geographic information system (GIS) for each tooth. Occlusal relief, defined as
      the ratio of 3D surface area to 2D planometric area of the occlusal table, was
      calculated and compared between wear stages, taxa, and sexes. The results failed
      to show a difference in occlusal relief between males and females of a given
      taxon, but did evince differences between wear stages and between taxa. A lack of
      significant interaction between wear stage and taxon factors suggests that
      differences in occlusal relief between chimpanzees and gorillas are maintained
      throughout the wear sequence. These results add to a growing body of information
      on how molar teeth change with wear, and how differences between primate species
      are maintained at comparable points throughout the wear sequence. Such studies
      provide new insights into form-function relationships, which will allow us to
      infer certain aspects of diet in fossils with worn teeth.

PMID- 12784285
TI  - New method to census primate groups: estimating group density of Japanese
      macaques by point census.
AB  - We devised a new method to estimate the density of primate groups in habitats
      that preclude the use of a line-transect census because the ground is too steep.
      We combined point census and group follows. From the number of groups counted at
      a fixed point for an hour, n, group density D was calculated: D = lambda n / pi.
      Lambda, the detectability constant, was a constant when distance-dependent
      detectability g(y) was regressed on a half-normal model: g(y) = e (-lambda y(2))
      and can be estimated by combining the information of group follow and point
      census. Using this method, we estimated the group density of Japanese macaques in
      Yakushima. A census area of 7 km(2) was divided into 28 grid squares (500 m x 500
      m). One observer was positioned at a point in each grid square, and those points
      were censused simultaneously for 4-6 days from 0600-0700 to 1500-1600 hr. Four
      troops were followed for 144 hr during the point census. Distance-dependent
      detectability closely correlated with the half-normal model. The detectability
      constant varied with the time of day, but it was not influenced by troop identity
      or topography. Group density was calculated to be 1.48 +/- 0.61 and 0.701 +/-
      0.432 groups/km(2) in the disturbed and undisturbed areas, respectively (95%
      confidence limit). "True" group density estimated by home range data was within
      the confidence limit calculated by a point census in the home range of the troops
      for two troops, suggesting that this method was valid. This method is applicable
      to other species as long as at least one group can be followed, because it
      satisfies the fundamental assumptions of point census, and the detectability does
      not seem to be biased by troop or topography.

PMID- 12784286
TI  - Resting energy metabolism of Goeldi's monkey (Callimico goeldii) is similar to
      that of other callitrichids.
AB  - The resting metabolic rates (RMRs) of six adult Goeldi's monkeys (Callimico
      goeldii) were measured using standard methods of open circuit respirometry during
      both the active (daytime) and inactive (nighttime) circadian phases for this
      species. One subject was measured both while she was pregnant and after she
      delivered a full-term, stillborn infant. Inactive-phase RMR within thermal
      neutrality (above 27.5 degrees C) averaged 288.5 +/- 30.8 ml O2/hr; active-phase
      RMR within thermal neutrality averaged 416.3 +/- 60.9 ml O2/hr. These values are
      74.6% and 107.6%, respectively, of the mammalian expected for animals of this
      body mass. During the inactive phase, metabolic rate increased an estimated 4.3%
      for every degree decline in temperature below 27.5 degrees C. The RMR in Goeldi's
      monkey is similar quantitatively and qualitatively to those of other captive
      callitrichids that have been studied, with active-phase RMR being at or slightly
      above the mammalian expected, and inactive-phase RMR being significantly reduced.
      We propose that this circadian pattern of RMR is a consequence of small body
      size, and is not a specific metabolic adaptation within the Callitrichidae. Thus
      we predict that metabolic studies measuring both circadian phases in other small
      primates will also find this pattern of reduced RMR during the inactive phase.
      The inactive-phase RMR within thermal neutrality of the pregnant female was not
      different from that measured after the stillbirth, despite an almost 15%
      difference in body mass. During pregnancy, however, the female was more
      metabolically responsive to temperature below thermal neutrality, and had a lower
      upper critical temperature (i.e., was less tolerant of heat).

PMID- 12784287
TI  - Noninvasive technique for the repeated sampling of salivary free cortisol in
      awake, unrestrained squirrel monkeys.
AB  - The use of noninvasive measures of hypothalamic-pituitary-adrenal (HPA) axis
      function is of growing interest among preclinical and clinical investigators.
      This report describes a method for the repeated assessment of salivary free
      cortisol in awake, unrestrained squirrel monkeys (Saimiri sciureus) based on a
      saliva sampling technique previously developed for rhesus monkeys. Individually
      housed adult male squirrel monkeys were trained to chew on dental rope attached
      to a pole, from which saliva was extracted by centrifugation and analyzed for
      cortisol by radioimmunoassay (RIA). Eight of nine monkeys readily acquired the
      task, reliably providing adequate saliva samples for the assay. Salivary free
      cortisol levels were examined in these subjects under basal conditions and in
      response to two types of neuroendocrine challenge. Levels of salivary free
      cortisol showed relatively low intra- and interindividual variability, with mean
      individual morning levels ranging between 17.1 and 37.9 microg/dl. Squirrel
      monkeys demonstrated a consistent daily rhythm in salivary free cortisol ranging
      from a high of 27.4 +/- 5.2 microg/dl (mean +/- SEM) at 12 P.M. to a low of 7.5
      +/- 1.6 microg/dl at 6 P.M. Intravenous (IV) challenges with 1 microg/kg ACTH, or
      10 and 50 microg/kg CRF resulted in significant increases in salivary free
      cortisol. The described sampling technique provides a reliable and sensitive
      means for repeated measurement of HPA activity in unrestrained, awake squirrel
      monkeys. In addition, our findings illustrate several features of HPA system
      rhythmicity and reactivity using salivary cortisol instead of blood plasma or
      serum.

PMID- 12784288
TI  - Development of the pharyngeal arches.
AB  - The oro-pharyngeal apparatus has its origin in a series of bulges that is found
      on the lateral surface of the embryonic head, the pharyngeal arches. The
      development of the pharyngeal arches is complex involving a number of disparate
      embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose
      development must be co-ordinated to generate the functional adult apparatus. In
      the past, most studies have emphasised the role played by the neural crest, which
      generates the skeletal elements of the arches, in directing pharyngeal arch
      development, but it has also become apparent that the other tissues of the
      arches, most notably the endoderm, also plays a prominent role in directing arch
      development. Thus pharyngeal arch development is more complex, and more
      consensual, than was previously believed.

PMID- 12784289
TI  - Further delineation of the phenotype associated with heterozygous mutations in
      ZFHX1B.
AB  - Mutations or deletions involving ZFHX1B (previously SIP1) have recently been
      found to cause one form of syndromic Hirschsprung disease (HSCR), associated with
      microcephaly, mental retardation, and distinctive facial features. Patients with
      the characteristic facial phenotype and severe mental retardation, but without
      HSCR, have now also been shown to have mutations in this gene. Mutations of
      ZFHX1B are frequently associated with other congenital anomalies, including
      congenital heart disease, hypospadias, renal tract anomalies, and agenesis of the
      corpus callosum (ACC). We present the clinical data and mutation analysis results
      from a series of 23 patients with this clinical syndrome, of whom 21 have proven
      ZFHX1B mutations or deletions (15 previously unpublished). Two patients with the
      typical features (one with and one without HSCR) did not have detectable
      abnormalities of ZFHX1B. We emphasize that this syndrome can be recognized by the
      facial phenotype in the absence of either HSCR or other congenital anomalies, and
      needs to be considered in the differential diagnosis of dysmorphism with severe
      mental retardation +/- epilepsy.

PMID- 12784290
TI  - Attitudes and distress levels in women at risk to carry a BRCA1/BRCA2 gene
      mutation who decline genetic testing.
AB  - Genetic testing enables women at risk for hereditary breast and/or ovarian cancer
      to find out whether they have inherited the gene mutation, and if so, to opt for
      undergoing frequent surveillance and/or prophylactic surgery. However, the option
      to know about one's genetic status is not always seen as a benefit by women at
      risk. Motives for declining genetic testing were explored in 13 women at 25% or
      50% risk to be a BRCA1/BRCA2 mutation carrier, who participated in a surveillance
      program for breast/ovarian cancer (the non-tested group). We hypothesized that
      high anxiety might be an important motive to decline testing. In addition, we
      investigated whether the non-tested group differed from a reference group of
      women who did undergo the test (tested group; n = 85) with regard to biographical
      factors, experience with cancer in relatives, and personality traits. Most non
      tested women (10/13) were satisfied with participating in the surveillance
      program. Four reported to feel emotionally unprepared to cope with the
      consequences of testing. Compared with the tested group, the non-tested women had
      similar mean distress levels (which were not high), but a higher education level,
      they were more often childless, showed more reluctance towards prophylactic
      surgery, were younger when first confronted with a relative affected with
      breast/ovarian cancer, and were longer aware of the genetic nature of the
      disease. This study showed that women were more likely to have thoroughly
      reflected on their decision not to undergo genetic testing, than to deny the
      whole issue due to high anxiety. Being confronted at a relatively young age with
      breast/ovarian cancer in a relative, and being aware of the genetic risk for a
      many years, may have resulted in the risk for cancer becoming an integrated part
      of their lives. However, generalization of these results to women who neither
      underwent the test nor participated in a surveillance program should be
      considered with caution.

PMID- 12784291
TI  - Prevalence of myotonic dystrophy in Israeli Jewish communities: inter-community
      variation and founder premutations.
AB  - In a comprehensive epidemiological survey among Jews living in Israel, the
      average prevalence of myotonic dystrophy (DM) was 15.7/10(5) (1 case in 6369)
      with intercommunity variations; the Ashkenazi Jews had the lowest rate, 5.7/10(5)
      (1 case in 17544) as compared to the rate in the Sephardim/Oriental Jews 20/10(5)
      (1 case in 5000) and the in the Yemenite Jews 47.3/10(5) (1 case in 2114). The
      rate of unrelated DM-sibships per 10(6) people of each community was used as an
      estimate of the transition rate from stable to unstable DMPK-(CTG)(n) alleles
      assuming that each transition is a beginning of a new DM sibship. This study
      indicated that the difference in the incidence of DM is a result of higher
      mutation rate in the non-Ashkenazi Jews (>50/10(6)) as compared to the rate in
      the Ashkenazi Jews (16.3/10(6)). The intragenic haplotype of the DM alleles was
      the same as that of the DM in many populations all over the world. However, two
      DM closely linked markers D19S207 and D19S112 were in linkage disequilibrium with
      the DM mutation in patients of Yemenite and Moroccan (the largest subgroup in the
      Sephardim Jews) extractions and not in the Ashkenazi patients. This observation
      indicated a common ancestral origin for the DM premutation in patients of the
      same ethnic origin. We concluded that the difference in the prevalence of DM
      among the Jewish communities is a consequence of founder premutations in the non
      Ashkenazi Jewish communities.

PMID- 12784292
TI  - Interaction of normal and expanded CAG repeat sizes influences age at onset of
      Huntington disease.
AB  - Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal
      expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have
      shown that the size of expanded CAG repeat is inversely associated with age at
      onset (AO) of HD. It is not known whether the normal Huntington allele size
      influences the relation between the expanded repeat and AO of HD. Data collected
      from two independent cohorts were used to test the hypothesis that the unexpanded
      CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the
      New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD
      affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found
      evidence supporting an interaction between the expanded and unexpanded CAG repeat
      sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The
      association was statistically significant when both cohorts were combined (P =
      0.012). The estimated heritability of the AO residual was 0.56 after adjustment
      for normal and expanded repeats and their interaction. An analysis of tertiles of
      repeats sizes revealed that the effect of the normal allele is seen among persons
      with large HD repeat sizes (47-83). These findings suggest that an increase in
      the size of the normal repeat may mitigate the expression of the disease among HD
      affected persons with large expanded CAG repeats.

PMID- 12784293
TI  - Gastroesophageal reflux and Cornelia de Lange syndrome: typical and atypical
      symptoms.
AB  - As previously reported, gastroesophageal reflux (GER) is a frequent and severe
      medical complication of Cornelia de Lange syndrome (CDLS). The incidence of GER
      and the correlation between its presence and degree, and the clinical phenotype
      of CDLS (mild/classical according to Van Allen classification) were evaluated in
      a series of 43 patients. The pattern of presenting symptoms and their clinical
      evolution after medical or surgical treatment were also studied. A pathological
      GER was evident in 28/43 (65%) CDLS patients. The incidence of the complication
      was not significantly different in patients with classical (93.3%) vs. mild
      phenotype (82.3%), whereas a strong correlation was present between the degree of
      the esophageal damage and the clinical phenotype. A behavioral symptom
      (hyperactivity) was the most frequent sign associated with the condition (85%).
      Our data confirm the high occurrence of GER in CDLS patients, independently from
      the CDLS clinical phenotype. Regarding the severity of the esophageal lesions, a
      significant difference between the two clinical CDLS phenotypes was found. The
      evaluation of the presenting symptoms and of their evolution during the treatment
      emphasizes the importance of behavioral symptoms as major signs of esophageal
      damage in CDLS.

PMID- 12784294
TI  - Severe musculoskeletal phenotype associated with an unbalanced t(6;10)
      translocation: clarification of the locus for this phenotype on distal 6p.
AB  - Larsen syndrome is a congenital condition consisting of multiple large joint
      dislocations associated with a distinctive facial appearance and frequently other
      abnormalities. The syndrome is probably genetically heterogeneous, with both
      dominant and recessive inheritance reported. Previously two cases have been
      reported where a Larsen-like syndrome was associated with unbalanced chromosomal
      translocations resulting in partial trisomy 1q and monosomy distal 6p. We now
      report a child with an unbalanced translocation resulting in a distal 6p deletion
      and partial trisomy 10q, who has Larsen-like features and has also severe
      developmental delay. A G-banded preparation revealed a karyotype
      46,XX,der(6),t(6:10)(p25;q25.2) and the breakpoint at 6p25 was confirmed by FISH
      using YAC probes (between 6p25 at D6s477/F13A1 and 6p24 at 6WI13606). Our case
      provides further evidence for a Larsen-like locus at distal 6p and reduces the
      potential critical region.

PMID- 12784295
TI  - Deletion of the SHOX gene in patients with short stature of unknown cause.
AB  - A fluorescence in situ hybridization (FISH) study was performed in 56 patients
      with short stature of unknown cause in order to establish the role of deletion of
      the SHOX gene in this population. FISH analysis was carried out on metaphase
      spreads and interphase lymphocytes from blood smears using a probe specific for
      the SHOX gene. Deletion of SHOX was found in four patients (7.1%). No skeletal
      abnormalities were detected in these patients either at the physical examination
      or at X-rays of the upper and lower limbs. Present results indicate that SHOX
      plays an important role also in short stature of unknown cause, and FISH analysis
      appears as an easy, appropriate, and inexpensive method for the detection of SHOX
      deletion.

PMID- 12784296
TI  - Interaction of genetic counselors with molecular genetic testing laboratories:
      implications for non-geneticist health care providers.
AB  - The availability of molecular genetic tests for the identification of mutant gene
      carriers, and for assessing individual genetic response to pharmacologic agents,
      infectious agents, and other environmental exposures, is expected to result in
      the increased use of the molecular genetic testing laboratory by primary care
      physicians. However, a number of concerns have been raised about such testing
      including the need for safeguards to protect patient privacy, and if the
      interface between genetic testing laboratories and the ordering physician
      facilitates the appropriate clinical use of the test result. In this study,
      genetic counselors were surveyed to determine their practices with regard to the
      clinical issues of informed consent and confidentiality in the context of genetic
      testing, and to assess their level of satisfaction with the reporting practices
      of molecular genetic testing laboratories. The results of this survey revealed
      that there is variability in the practices of genetic counselors with regard to
      obtaining informed consent, and that there are areas for improvement with regard
      to molecular genetic test reports, particularly in terms of interpretation of
      results.

PMID- 12784297
TI  - Vocal cord abnormalities in Williams syndrome: a further manifestation of elastin
      deficiency.
AB  - Williams syndrome (WS) is due to a deletion in the WS critical region at 7q11.23
      which includes the elastin gene (ELN). One of the most characteristic features of
      this disorder is a harsh, brassy, or hoarse voice but the etiology of the vocal
      characteristics are unknown. We report two patients with WS who had bilateral
      vocal cord abnormalities, bringing to four the number of children with WS in whom
      such defects have been documented. We suggest that vocal cord abnormalities may
      be a far more common feature of WS than has been previously suspected, and that
      mild vocal cord dysfunction caused by abnormal vocal cord elastin may be the
      cause of the hoarse voice in this condition.

PMID- 12784298
TI  - Pregnancy outcome and prenatal diagnosis of sex chromosome abnormalities in
      Hawaii, 1986-1999.
AB  - Sex chromosome abnormalities such as Turner syndrome, Klinefelter syndrome,
      triple X syndrome, and 47,XYY can be prenatally diagnosed and electively
      terminated. This investigation examined the pattern of pregnancy outcome of
      prenatally and postnatally diagnosed sex chromosome abnormalities in Hawaii
      during 1986-1999 and calculated prenatal diagnosis and subsequent elective
      termination rates for various factors. Data were obtained from a statewide
      population-based birth defects registry. The study included 205 detected sex
      chromosome abnormality cases of which 93 (45%) were live births, 18 (9%) late
      fetal deaths, 37 (18%) early fetal deaths, and 57 (28%) elective terminations.
      Pregnancy outcome distribution varied by type of sex chromosome abnormality.
      Prenatal diagnosis was reported for 132 (64%) of the cases, of which 46 (35%)
      were subsequently electively terminated. Eleven cases were elective terminations
      where the sex chromosome abnormality was diagnosed after delivery. Elective
      termination rates subsequent to prenatal diagnosis differed by sex chromosome
      abnormality, being highest for 45,X (54%), followed by 47,XXY (46%), 47,XYY
      (29%), and 47,XXX (17%). Although prenatal diagnosis rates increased
      significantly over the time period (P = 0.006), the subsequent elective
      termination rate declined slightly, albeit the trend was not statistically
      significant (P = 0.440). The prenatal diagnosis rate was highest for the 35-39
      year maternal age group, although this age group did not have subsequent elective
      termination rates higher than other maternal age groups. Pregnancy outcome
      distribution and prenatal diagnosis and subsequent elective termination of sex
      chromosome abnormalities appeared to depend on the type of sex chromosome
      abnormality, year of delivery, and maternal age.

PMID- 12784299
TI  - First-year mortality rates for selected birth defects, Hawaii, 1986-1999.
AB  - Birth defects have been the leading cause of infant death in the United States
      for over the last decade. However, there is little population-based data on the
      first-year mortality rates for many specific birth defects and the factors that
      may affect these mortality rates. This investigation examined the first-year
      mortality rates for 54 selected birth defects of various organ systems in Hawaii
      during 1986-1999 using data from a population-based birth defects registry and
      evaluated the impact of the presence of chromosomal abnormalities and other
      structural birth defects and the year of delivery on the mortality rates.
      Mortality rates varied widely by defect, being highest for anencephaly (100%),
      trisomy 13 (82%), and trisomy 18 (74%), while no first-year deaths were reported
      for glaucoma, bladder exstrophy, and persistent cloaca. The majority (36 of 54 or
      67%) of the birth defects had a mortality rate of less than 25%. Among the 51
      structural birth defects, 38 (75%) had higher first-year mortality rate for cases
      with chromosomal abnormalities and 42 (82%) had higher first-year mortality rates
      for cases with other major structural birth defects. The mortality rate among
      1986-1992 deliveries was higher than the mortality rate among 1993-1999
      deliveries for 37 (69%) of the 54 birth defects. This study indicates that first
      year mortality rates vary widely by type of birth defect, although the mortality
      rate for the majority of birth defects is relatively low. The presence of a
      chromosomal abnormality or other structural birth defect increases the mortality
      rate, and mortality rates for the majority of birth defects have declined in
      Hawaii during the study period.

PMID- 12784300
TI  - Epidemiology of triploidy in a population-based birth defects registry, Hawaii,
      1986-1999.
AB  - Triploidy is a highly lethal chromosomal abnormality with few fetuses surviving
      to term. Triploidy has not been extensively studied using data from a population
      based birth defect registry. This investigation examined the epidemiology of
      triploidy using data from the Hawaii Birth Defects Program (HBDP) and compared
      its findings with the literature. Of the 38 identified cases of triploidy
      delivered in Hawaii during 1986-1999, 31 (82%) were early fetal deaths, 3 (8%)
      late fetal deaths, and 4 (11%) elective terminations. The distribution of cases
      by sex chromosome combination was 15 (39%) XXX, 22 (58%) XXY, and 1 (3%) XYY.
      Triploidy was prenatally diagnosed in eight (21%) of the cases, of which four
      were electively terminated, two resulted in early fetal death, and two resulted
      in late fetal death. The detected triploidy prevalence in 1993-1999 was higher
      than the prevalence in 1986-1992, although the difference was not statistically
      significant (rate ratio (RR) 1.20, 95% confidence interval (CI) 0.73-1.86). The
      detected triploidy prevalence for maternal age of 35 years or greater was
      significantly higher than the prevalence for maternal age less than 35 years (RR
      4.07, 95% CI 2.22-6.83). In spite of under detection of cases, many aspects of
      the epidemiology of triploidy identified in a population-based birth defects
      registry were consistent with that reported in the literature.

PMID- 12784301
TI  - Analysis of 40 sporadic or familial neonatal and pediatric cases with severe
      unexplained respiratory distress: relationship to SFTPB.
AB  - We have analyzed surfactant protein B (SP-B) and its encoding gene (SFTPB, MIM
      178640) in 40 unrelated pediatric patients with unexplained respiratory distress
      (URD). There was high consanguinity (eight kindreds) and an underlying autosomal
      recessive trait could be inferred in most cases, with overall high sex ratio
      (32/17) suggesting proband's gender to impact on penetrance. The
      clinical/biological presentations fitted into three major nosologic frameworks.
      I: SP-B deficiency (nine probands), complete or incomplete, with
      homozygous/compoundly heterozygous mutations identified (six probands), including
      one from the population isolate of Reunion Island (496delG). In addition, there
      was a consanguineous kindred in which incomplete deficiency was unambiguously
      unlinked to SFTPB. II: pulmonary alveolar proteinosis (PAP, 19 probands), with
      typical storage of PAS-positive material within the alveoli with foamy
      macrophages and variable interstitial reaction, which was diagnosed in most
      patients from Reunion Island. In contrast to previously published findings,
      mutation and/or segregation analyses excluded SFTPB as a disease locus, although
      slight metabolic derangement related to SP-B and/or mild SFTPB changes could
      somehow contribute to disease. III: URD without evidence for SP-B deficiency or
      PAP (12 probands), equally unlinked to SFTPB, although a single patient had a
      possibly causal, maternally-derived, heterozygous genetic change (G4521A). The
      population frequency of five known and four novel SNPs was studied, providing as
      many potential markers for pulmonary disease related to SFTPB. Overall, URD was
      found to be heterogeneous, both phenotypically and genetically, even in
      population isolates where a founder effect might have been expected. When disease
      loci are identified, patient genotyping will be crucial as a diagnostic aid, for
      devising proper treatment, and as a basis for genetic counseling.

PMID- 12784302
TI  - Understanding why negative genetic test results sometimes fail to reassure.
AB  - A proportion of those receiving negative results following predictive genetic
      testing desire future bowel screening. This is despite a negative result meaning
      a general population risk of 1:7500 and despite bowel screening being experienced
      as aversive and clinically unnecessary. This study aimed to investigate
      perceptions of risk, illness, and tests amongst those receiving negative results
      following predictive genetic testing. Interviews with nine people receiving
      negative genetic test results for familial adenomatous polyposis (FAP) were
      analyzed using the qualitative method, interpretative phenomenological analysis
      (IPA). Those not reassured by negative genetic test results perceived a
      continuing risk to themselves and to their children. Two sets of perceptions
      emerged that might explain this: (1). perceptions of the genetic basis of the
      condition (FAP). Although the condition was perceived to be genetic, genetic
      status was seen as transient, so a result today could not predict the future. The
      condition was also seen as caused by factors other than genes, so information
      about only one risk factor could not be reassuring. (2). Perceptions of the
      genetic test. There was a lack of conviction in the ability of the genetic test,
      based on a blood sample, to predict a disease located in the bowel. These results
      suggest that some individuals receiving negative test results are not reassured
      because of their representations of the cause of their condition and the nature
      of the tests they undergo. It may be that eliciting and, when appropriate,
      changing people's representations prior to testing may enable those receiving
      negative results to be more reassured about their residual risk.

PMID- 12784303
TI  - Application of a protocol for the detection of disorders of sialic acid
      metabolism to 124 high-risk Brazilian patients.
AB  - Lysosomal storage disorders (LSD) present great clinical variability. Included in
      this group are sialic acid metabolism disorders (SAMD). In the present study, we
      describe the application of a 3-step protocol for the diagnosis of SAMD,
      including (1). oligosaccharide and sialyloligosaccharide chromatography; (2).
      quantitative determination of sialic acid; and (3). measurement of neuraminidase
      activity. Application of our protocol to 124 individuals at risk for SAMD led to
      the diagnosis of five affected patients, two with type I sialidosis, one with
      type II sialidosis, and two with galactosialidosis. Due to its simplicity and
      efficiency, we propose the use of this protocol for the diagnostic evaluation of
      patients with suspected SAMD, which could be specially useful to non-specialized
      laboratories and to services located in developing countries.

PMID- 12784304
TI  - A new autosomal recessive syndrome with Zellweger-like manifestations.
AB  - A son and daughter of consanguineous Ashkenazi Jewish parents presented with
      phenotypic features that are typically seen in Zellweger syndrome: high forehead,
      broad nasal bridge, epicanthal fold, upslanting palpebral fissures, and
      micrognathia. In addition to the physical anomalies, they also have severe
      psychomotor retardation and hypotonia. However, results of peroxisomal studies
      including very long chain fatty acids and plasmalogen functions, were normal.
      There was partial deficiency of respiratory chain complexes. We suggest that this
      is a new autosomal recessive syndrome that could be due to a nuclear-encoded
      mitochondrial defect.

PMID- 12784305
TI  - Deletion of chromosome region 18q21.1 --> 18q21.3 in a patient without clinical
      features of the 18q- phenotype.
AB  - In a 16-month-old boy referred because of developmental delay and asymmetric
      motor development, chromosome analysis showed an aberrant chromosome 18 in all 25
      metaphases examined. The chromosome aberration was initially interpreted either
      as an interstitial deletion of chromosome region 18q21.1 --> 18q21.3 or an
      unbalanced translocation involving the distal part of the long arm of chromosome
      18. Chromosome microdissection in combination with fluorescence in situ
      hybridization demonstrated that the aberrant chromosome 18 had an interstitial
      deletion, the karyotype being: 46,XY,del(18)(q21.1q21.3). At age 27 months, his
      development was moderately retarded. He showed craniofacial asymmetry but no
      other anomalies. The clinical and cytogenetic findings are compared with
      previously reported patients with a terminal or interstitial deletion in the long
      arm of chromosome 18.

PMID- 12784306
TI  - New variant of acro-renal field defect.
AB  - We describe two patients with a new variant of acro-renal field defect. The first
      was a full-term, small-for-gestational-age female infant who showed preaxial
      polydactyly of the right hand and horseshoe kidney on abdominal ultrasonographic
      examination. In addition, there was a single umbilical artery and some mild
      facial errors of morphogenesis. The second patient, a full-term male infant, had
      horseshoe kidney and left hand ectrodactyly. Various renal abnormalities have
      been described in the literature, but there are no reports on horseshoe kidney as
      part of acro-renal field defect. We suggest that acro-renal field defect should
      not be regarded as a definitive diagnosis, but only as a starting point for the
      search for various conditions.

PMID- 12784307
TI  - Terminal deletion of chromosome 5p in a patient with phenotypical features of
      Lujan-Fryns syndrome.
AB  - We report a young man with phenotypical features suggestive of Lujan-Fryns
      syndrome and behaviour of an autistic spectrum disorder, who has a subtle
      terminal deletion of the short arm of chromosome 5. Individuals reported
      previously with a similar chromosomal abnormality have had developmental delay
      and a 'breathy, raspy' voice. It may be appropriate to consider screening
      patients with a phenotype suggestive of Lujan-Fryns syndrome by fluorescence in
      situ hybridisation (FISH) using a probe for the subtelomeric region of the short
      arm of chromosome 5.

PMID- 12784308
TI  - Inv(X)(p21.1;q22.1) in a man with mental retardation, short stature, general
      muscle wasting, and facial dysmorphism: clinical study and mutation analysis of
      the NXF5 gene.
AB  - We describe a 59-year-old male (patient A059) with moderate to severe mental
      retardation (MR) and a pericentric inversion of the X-chromosome:
      inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle
      wasting, and facial dysmorphism. Until now, no other patients with similar
      clinical features have been described in the literature. Molecular analysis of
      both breakpoints led to the identification of a novel "Nuclear RNA export factor"
      (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted
      with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and
      its neighboring homologue, the NXF2 gene was performed in 45 men with various
      forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR.
      In the NXF5 gene four nucleotide changes: one intronic, two silent, and one
      missense (K23E), were identified. In the NXF2 gene two changes (one intronic and
      one silent) were found. Although none of these changes were causative mutations,
      we propose that NXF5 is a good candidate gene for this syndromic form of XLMR,
      given the suspected role of NXF proteins is within mRNA export/transport in
      neurons. Therefore, mutation screening of the NXF gene family in phenotypically
      identical patients is recommended.

PMID- 12784309
TI  - Short trunk stature, brachydactyly, and platyspondyly in three sibs: a new form
      of brachyolmia or a new skeletal dysplasia?
AB  - We present a 27-year-old girl with short trunk stature, generalized rectangular
      platyspondyly and strike precocious calcification of costal cartilage. She had
      also brachydactyly, small nails, strabismus and delay of menarche. Her 16-year
      old sister had also short trunk stature with severe kyphoscoliosis, hearing loss,
      brachydactyly, platyspondyly and mild precocious calcification of costal
      cartilages. Their 12-year-old brother had short trunk stature, kyphoscoliosis,
      brachydactyly, and platyspondyly but did not show precocious calcification of
      costal cartilage. The patients shared the following features: short trunk
      stature, brachydactyly, severe rectangular platyspondyly, broad and short femoral
      necks and hypoplasia of the ileum. In addition, the older sister had strike
      precocious calcification of costal cartilage while her sister and brother had
      severe kyphoscoliosis. Although short trunk stature and severe rectangular
      platyspondyly without significant epiphyseal or metaphyseal changes were in favor
      of Hobaek type brachyolmia, this diagnosis was not considered, both because,
      there were no specific radiological findings of this syndrome, such as elongated
      vertebral bodies extending beyond the pedicles laterally and all of the patients
      had brachydactyly which was not present in Hobaek type brachyolmia. The parents
      were healthy and first cousins signifying autosomal recessive inheritance. We
      considered that the patients could be affected by a new distinct autosomal
      recessive type brachyolmia or a new skeletal dysplasia.

PMID- 12784310
TI  - Alport syndrome with diffuse leiomyomatosis.
AB  - Alport syndrome (AS) is a hereditary nephropathy with hematuria progressing to
      end-stage renal failure (ESRF), sensorineural deafness, and specific eye signs
      (lenticonus, macular flecks, and congenital cataracts). Inheritance is X-linked
      in about 85% of the cases, caused by different mutations in the COL4A5 gene.
      Rarely AS is seen in combination with diffuse leiomyomatosis (DL). DL is a
      tumorous process involving smooth muscle cells, mostly of the esophagus, but also
      of the tracheobronchial tree and the female genital tract. Characteristically,
      the patients have deletions of the 5'-end of both the COL4A5 and the COL4A6
      genes, respectively. We here present a 9-year-old boy who was admitted because of
      a newly diagnosed sensorineural deafness. He was born with cataracts and
      presented symptoms of dysphagia and bronchial irritation in the first year of
      life. Macroscopic hematuria was first noticed at 2 years during a febrile
      infection. Since early childhood the boy suffered from severe constipation.
      Taking together these symptoms, the diagnosis of Alport syndrome with diffuse
      leiomyomatosis (AS-DL) has to be considered. Genetic analysis demonstrated the
      predicted deletion of the COL4A5/COL4A6 genes.

PMID- 12784311
TI  - Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL).
AB  - Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) is a distinctive form
      of skeletal dysplasia characterized by severe dwarfism, generalized articular
      hypermobility, and progressive spinal malalignment. We report on a patient with
      SEMDJL, who presented with all the characteristic orthopedic manifestations of
      the disorder, required multiple operative procedures, and has the longest
      reported follow-up and survival into adulthood with a favorable outcome. We
      describe all the clinical and radiographic findings that can allow an early
      diagnosis of this type of skeletal dysplasia, which can lead to profound
      disability with potentially lethal spinal and pulmonary complications in early
      childhood. In view of the severe clinical and genetic implications, diagnostic
      precision is of vital importance, particularly since the disorder is currently
      believed to be more common than initially reported.

PMID- 12784312
TI  - Mandibuloacral dysplasia with absent breast development.

PMID- 12784313
TI  - Clinical findings and phenotype in a toddler with 48,XXYY syndrome.

PMID- 12784314
TI  - Otocephaly and holoprosencephaly in only one monozygotic twin.

PMID- 12784315
TI  - Genetic drift. A few moments.

PMID- 12784316
TI  - Comments on "osteopathia striata cranial sclerosis: non-random X-inactivation
      suggestive of X-linked dominant inheritance".

PMID- 12784317
TI  - Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets
      (Simvast and Zocor) in healthy human volunteers.
AB  - The pharmacokinetics of two brands of simvastatin 40 mg tablets were compared in
      24 healthy human volunteers after a single oral dose in a randomized cross-over
      study, conducted at IPRC, Amman, Jordan. Reference (Zocor, MSD, Netherlands) and
      test (Simvast, Julphar, UAE) products were administered to fasted volunteers;
      blood samples were collected at specified time intervals, plasma separated and
      analyzed for simvastatin and its active metabolite (beta-hydoxy acid) using a
      validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical
      Sciences - USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0
      variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined
      from plasma concentration-time profile for both formulations and were compared
      statistically to evaluate bioequivalence between the two brands, using the
      statistical modules recommended by FDA. The analysis of variance (ANOVA) did not
      show any significant difference between the two formulations and 90% confidence
      intervals fell within the acceptable range for bioequivalence. Based on these
      statistical inferences it was concluded that the two brands exhibited comparable
      pharmacokinetic profiles and that Julphar's Simvast is bioequivalent to Zocor of
      MSD, Netherlands.

PMID- 12784318
TI  - Pharmacokinetic scaling of SJ-8029, a novel anticancer agent possessing
      microtubule and topoisomerase inhibiting activities, by species-invariant time
      methods.
AB  - This study examined the pharmacokinetic disposition of SJ-8029, a novel
      anticancer agent possessing microtubule and topoisomerase inhibiting activities,
      in mice, rats, rabbits and dogs after i.v. administration. The serum
      concentration-time curves of SJ-8029 were best described by tri-exponential
      equations in all these animal species. The mean Cl, V(ss) and t(1/2) were 0.3
      l/h, 0.1 l and 63.2 min in mice, 1.5 l/h, 1.6 l and 247.7 min in rats, 13.8 l/h,
      39.6 l and 245.9 min in rabbits, and 29.2 l/h, 44.6 l and 117.4 min in dogs,
      respectively. Based on animal data, the pharmacokinetics of SJ-8029 were
      predicted in humans using simple allometry and also by several species-invariant
      time transformations using kallynochron, apolysichron and dienetichron times. The
      human pharmacokinetic parameters of Cl, V(ss) and t(1/2) predicted by the simple
      allometry and various species-invariant time methods were 50.4-145.0 l/h, 369.0
      579.8 l and 242.0-1448.3 min, respectively. These preliminary parameter values
      may be useful in designing early pharmacokinetic studies of SJ-8029 in humans.

PMID- 12784319
TI  - Time dependent pharmacokinetics of albendazole in human.
AB  - The pharmacokinetics of the main metabolites of albendazole (albendazole
      sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-SO2) were studied in 12 healthy
      human volunteers in a double blind design on the first and last days of oral
      administration of 800 mg albendazole daily for 15 days. No significant
      differences were observed in C(max), T(max) and V(d)/F of ABZ-SO, whereas the
      AUC, AUMC and T(1/2) of this metabolite were significantly reduced and Cl/F was
      significantly increased in multiple dosing. There were also no significant
      differences in the C(max), T(max), V(d)/F and T(1/2) of ABZ-SO2, whereas the AUC
      and AUMC of this metabolite were significantly reduced and Cl/F was significantly
      increased in multiple dosing. These observations suggest time dependent
      pharmacokinetics of albendazole (observed for ABZ-SO and ABZ-SO2), which was
      explained on the basis of the induction of enzymes involved in the metabolism of
      ABZ-SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in
      multiple dosing.

PMID- 12784320
TI  - Lack of interaction between HEPP, a new antiepileptic agent, and carbamazepine in
      rabbits.
AB  - The effect of the combination of a new anticonvulsant drug HEPP and carbamazepine
      (CBZ) on the pharmacokinetics of HEPP and CBZ was investigated using rabbits as
      an animal model. The study was performed in 18 male New Zealand white rabbits
      which were randomly divided into three groups, according to a balanced incomplete
      block design of three treatments and two periods. Plasma concentrations for HEPP
      and CBZ were assayed using HPLC methods. The results showed that the
      pharmacokinetic parameters C(max), AUC and t(1/2) were not statistically
      different when HEPP was administered alone and with CBZ, (AUC(0-alpha) 82.86+/
      19.40 vs 83.24+/-12.56 microg h ml(-1); t( 1 2 beta) 3.40+/-0.29 vs 3.36+/-0.45
      h; C(max) 18.93+/-2.99 vs 19.79+/-2.68 microg ml(-1) and T(max) 1.27+/-0.16 vs
      1.22+/-0.11 h for HEPP alone and HEPP plus CBZ respectively. Evaluation of the
      pharmacokinetic parameters of CBZ showed, AUC(0-inf) 61.5+/-21.7 vs 67.4+/-23.8
      microg h ml(-1); t(12) 4.60+/-1.54 vs 4.41+/-1.35 h; C(max) 8.45+/-3.83 vs 8.70+/
      2.59 microg ml(-1) when the drug was administered alone and CBZ plus HEPP,
      respectively. Our data indicate that there is no effect on the pharmacokinetics
      of either HEPP or CBZ, when they are administered simultaneously.

PMID- 12784321
TI  - Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in
      normolipaemic and hyperlipidaemic obese subjects.
AB  - The lipophilic beta-adrenoreceptor antagonist propranolol and hydrophilic
      atenolol have been studied to define their pharmacokinetic and pharmacodynamic
      characteristics in obese patients. A total of 43 subjects were allocated into
      three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese
      normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover
      method with an interval of 2 weeks was applied for oral 80 mg propranolol and
      oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic
      blood pressure were recorded during 24 h. At each time-point of measurement blood
      serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic
      parameters of the drugs were calculated using a one-compartment open model for
      extravascular administration. There were no statistically significant differences
      in blood serum concentrations of propranolol between the studied groups. The
      concentrations of atenolol were significantly lower in both normolipaemic and
      hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of
      propranolol in obese patients with hyperlipidaemia were noted. In the case of
      water-soluble atenolol, the AUC, C(max), Cl/(F x BW) were significantly lower in
      obese hyperlipidaemic and normolipaemic patients in comparison with lean
      subjects. The pharmacodynamic effects of propranolol and atenolol in obese and
      lean subjects were of similar magnitude. The observed differences between obese
      and non-obese persons were clinically not relevant.

PMID- 12784322
TI  - Effect of length of sampling schedule and washout interval on magnitude of drug
      carryover from period 1 to period 2 in two-period, two-treatment bioequivalence
      studies and its attendant effects on determination of bioequivalence.
AB  - The relationships between post-dosing blood sampling schedules and length of
      washout interval on the percent of drug carryover into period 2, in a two
      treatment, two-period, crossover bioequivalence study was investigated. Observed
      simulations were done using a two-compartment model with a beta half-life of 100
      h, sampling to 200 and 300 h, followed by 1 to 4 washout half-lives. These data
      were compared with simulations with sampling for 200 and 300 h and no carryover
      between periods (i.e. true data) and used to establish the per cent carryover.
      Pseudo-observed concentration period 2 data were also generated for an
      experimental amiodarone bioequivalence study by adding either 5%, 10% or 50% of
      the period 2 C(max) value to the observed concentrations of selected subjects
      (i.e. those with longest half-lives) to give a pseudo-plasma concentration
      profile. Further investigation via simulation was done by including or excluding
      subjects with time 0 concentrations of 1%-10% of period 2 C(max). The simulated
      data indicated that up to a 3% carryover of AUC into the second period of a
      bioequivalence study had no effect on the power of the 90% CI for AUC and C(max).
      For amiodarone, second period pre-dose drug concentrations equal to as much as
      50% of the observed period 2 C(max) value had less effect on the 90% CI (i.e.
      compared with the true data) for AUC and C(max) than did subject deletion.

PMID- 12784323
TI  - Long-term trends in cancer mortality in the United States, 1930-1998.
AB  - BACKGROUND: Progress against cancer can be examined by analyzing long-term trends
      in cancer incidence and mortality. The recent directive from the U.S. Department
      of Health and Human Services to adopt the 2000 U.S. standard population for the
      age adjustment of death rates prompted the American Cancer Society to update
      historical cancer mortality statistics using the new standard. METHODS: Mortality
      data were abstracted by race, gender, year, and age at death for 1930 through
      1959 from annual volumes of Vital Statistics of the United States. For 1960
      through 1998, these data were obtained from data tapes provided by the National
      Center for Health Statistics. Two U.S. standard million populations (1970 and
      2000) were used to calculate age-adjusted rates. Average annual percent change
      was estimated for each decade by site, gender, and age, and the statistical
      significance of the change was assessed at p < 0.05. RESULTS: After long-term
      increases or mostly level trends that date from the 1930s for some sites, death
      rates for cancers of the lung (in males), prostate, female breast, colon-rectum,
      pancreas, leukemia, and ovary were decreasing in the 1990s. Liver cancer death
      rates were increasing in the 1990s. Throughout the study period, death rates for
      female lung cancer increased, while death rates for stomach and uterine cancers
      declined. CONCLUSIONS: The trends of decreasing cancer death rates for the
      leading cancer sites in the 1990s are encouraging. However, surveillance
      researchers must continue to monitor these declines to assess whether the
      progress seen in this decade persists. Efforts also must be made to study the
      sites with increasing trends and identify potential underlying causes.

PMID- 12784324
TI  - Has the investment in public cancer education delivered observable changes in
      knowledge over the past 10 years?
AB  - BACKGROUND: During the 1990s, Western countries, such as Australia, directed
      substantial funds toward public cancer education. An important indicator of
      whether this investment has been worthwhile is a shift over time in the
      proportion of the population who have accurate knowledge regarding cancer.
      METHODS: In the year 2000, a cross-sectional telephone survey was administered to
      685 residents selected from the New South Wales (Australia) Electronic White
      Pages telephone directory. This study replicated in part a survey conducted in
      1989. RESULTS: In the 2000 survey, smoking (96.0%) and sun exposure (80.4%) were
      well-known as risk factors for lung cancer and melanoma, respectively. However,
      community knowledge of risk factors for colorectal, breast, cervical, and
      prostate cancer was poor. Most respondents were able to nominate mammograms
      (82.2%) and Pap tests (86.8%) as screening tests for breast and cervical cancer,
      respectively. Approximately two-thirds of the sample were able to nominate foods
      that reduce the risk of developing cancer. Compared with the 1989 data, there
      appeared to have been improvements in community knowledge of mammograms as a
      screening test for breast cancer. For the other cancers, knowledge gains appeared
      smaller or marginal. With regard to the lifetime risk of developing these
      cancers, community understanding remains poor. Predictors of greater knowledge
      include a higher level of education. CONCLUSIONS: Where ongoing investments have
      been made, like in the case of breast cancer education, there have been
      improvements in community knowledge. However, major challenges remain. Potential
      targets for future public education campaigns are discussed.

PMID- 12784326
TI  - Seeking the solution to the problem of metastatic renal carcinoma.

PMID- 12784327
TI  - Sentinel lymph nodes.

PMID- 12784328
TI  - Hepatic steatosis in patients with chronic hepatitis C virus infection. Another
      risk factor for hepatocellular carcinoma?

PMID- 12784329
TI  - A simple model of breast carcinoma growth may provide explanations for
      observations of apparently complex phenomena.
AB  - BACKGROUND: There has been great debate regarding the importance of ductal
      carcinoma in situ (DCIS) in the breast. Autopsy results that demonstrate a much
      greater number of these lesions compared with the number of invasive carcinomas,
      and the numbers of deaths from breast carcinoma each year have been cited as
      evidence that DCIS rarely leads to invasion and death. These analyses have
      overlooked the fact that, to sustain a rate of detection each year, there would
      have to be a reservoir of undetected breast carcinomas growing in the population.
      The authors developed a simple model that makes this clear. In addition, complex
      phenomena have been suggested to explain why invasive breast disease may grow
      more rapidly among very young women and more slowly among the very old. A simple
      model provides some insight that may simplify the explanation of these
      observations. METHODS: The simple model of breast carcinoma growth assumes that
      there are three types of breast carcinoma that begin each year in a cohort of
      women. It assumes that all breast carcinomas begin as DCIS and take 9 years to go
      from a single cell to an invasive lesion for the slowest growing lesions, 6 years
      for intermediate growing DCIS lesions, and 3 years for fast-growing DCIS lesions.
      Furthermore, once an invasive clone forms, the model assumes that it will double
      in 60 days for fast-growing lesions, 120 days for intermediate growing lesions,
      and 180 days for slow-growing lesions. Three new tumors begin to grow in each
      successive year (one of each type). The model uses simple vectors that are
      defined by the size of the tumors and the time since tumor initiation, and it
      assumes that all tumors are detected when they reach 2 cm in greatest dimension.
      The model can be used to show graphically how many undetected tumors (DCIS as
      well as invasive carcinomas) there may be in the population to sustain the
      detection of three invasive tumors each year. RESULTS: Using the assumptions
      described above, the model showed that, by the time the first slow-growing breast
      carcinoma reaches 2 cm in greatest dimension, there will be 29 other slow-growing
      tumors that have not reached that size (9 DCIS and 20 smaller invasive
      carcinomas), 19 moderately growing tumors (6 DCIS and 13 smaller invasive
      carcinomas), and 9 fast-growing tumors (3 DCIS and 6 smaller invasive
      carcinomas). This means that, for every three breast tumors that reach 2 cm, the
      model predicted that there would be another 57 tumors (39 smaller invasive
      carcinomas and 18 DCIS) that would be undetected "below the surface". The model
      showed clearly that faster growing tumors would be expected to predominate among
      the youngest women, because they are the first to "reach the surface"; and, if
      the number of newly initiated tumors decreases with age, then there will be more
      of the slowest growing tumors that are left to reach the surface among the oldest
      women in the population. CONCLUSIONS: Even if the authors' assumptions are
      incorrect, their model made it clear that, to diagnose several breast carcinomas
      per 1000 women each year means that there have to be many more undetected
      carcinomas in the population to sustain the rate of detection. Although the model
      did not prove that DCIS may become potentially invasive and lethal, it did
      demonstrate that, even if all of these in situ lesions become invasive and
      lethal, many more DCIS lesions would have to be expected in the population than
      the number of invasive carcinomas detected each year and the number of deaths
      from breast carcinoma each year. Furthermore, the model provided a simple, purely
      mechanical illustration that may explain the preponderance of faster growing
      breast carcinomas among very young women and the preponderance of slower growing
      tumors among elderly women.

PMID- 12784330
TI  - Total RNA yield and microarray gene expression profiles from fine-needle
      aspiration biopsy and core-needle biopsy samples of breast carcinoma.
AB  - BACKGROUND: Gene expression profiling should be applicable to needle biopsy
      samples if microarray technology is to become practically useful for clinical
      research or management of breast carcinoma. This study compared gene expression
      profiles derived from fine-needle aspiration biopsy (FNAB) and from core needle
      biopsy (CBX). METHODS: Total RNA was extracted from single FNAB and CBX samples.
      Corresponding pairs of FNAB and CBX were analyzed for similarity of gene
      expression profiles using cDNA microarrays that contain 30721 human sequences. A
      subset of genes that distinguished CBX samples from FNAB samples was evaluated in
      a larger group of needle biopsy samples and in a published genomic database
      derived from 78 sporadic breast carcinomas with known clinical outcome. RESULTS:
      Sixty-eight patients with newly diagnosed breast carcinoma were included in the
      current study. Sixty-five patients underwent FNAB (17 had both FNAB and CBX) and
      3 underwent CBX only. Extracted RNA was of suitable quality for hybridization in
      46 (71%) FNABs and 15 (75%) CBXs. Total RNA yield in those samples was similar
      for single-pass FNAB (mean = 3.6 microg and median = 2.2 microg; n = 46) and CBX
      (mean = 2.8 microg and median = 2.0 microg; n = 15), with 1 microg or more of
      total RNA in all cases. Transcriptional profiling was performed successfully in
      all cases when it was attempted, in a total of 50 samples (38 FNABs and 12 CBXs),
      including matched FNAB and CBX samples from 10 patients. There were differences
      in gene expression profiles in 10 matched FNAB and CBX sample pairs. Genes that
      were expressed differently in CBX samples, compared with FNAB samples, were
      recognized as being predominantly from the endothelium, fibroblasts,
      myofibroblasts or smooth muscle, and histiocytes. Corresponding microscopic cell
      counts from FNABs demonstrated means of 80% tumor cells, 15% lymphocytes, and 5%
      stromal cells, whereas CBXs contained 50% tumor cells, 20% lymphocytes, and 30%
      stromal cells. Considering that CBXs are approximately six-fold richer in
      nonlymphoid stromal cells than FNABs and that CBXs differentially express a set
      of recognized stromal genes, the authors used these biopsies to define a
      transcriptional profile of breast carcinoma stroma. A set of 120 genes
      differentially expressed in CBXs was assessed independently in a published breast
      carcinoma genomic database to classify breast carcinomas based on stromal gene
      expression. Subgroups of tumors with low or high stromal signal were identified,
      but there was no correlation with the development of systemic metastases within 5
      years. CONCLUSIONS: Both FNAB and CBX yield a similar quality and quantity of
      total RNA and are suitable for cDNA microarray analyses in approximately 70-75%
      of single-pass samples. Transcriptional profiles from FNAB and CBX of the same
      tumor generally are similar and are driven by the tumor cell population. The
      authors concluded that each technique has relative advantages. The FNABs provide
      transcriptional profiles that are a purer representation of the tumor cell
      population, whereas transcriptional profiles from CBXs include more
      representation from nonlymphoid stromal elements. Selection of the preferred
      needle biopsy sampling technique for genomic studies of breast carcinomas should
      depend on whether variable stromal gene expression is desirable in the samples.

PMID- 12784331
TI  - Central nervous system metastases in women who receive trastuzumab-based therapy
      for metastatic breast carcinoma.
AB  - BACKGROUND: Women with HER-2 overexpressing metastatic breast carcinoma benefit
      from trastuzumab-based therapy, but trastuzumab does not cross the blood-brain
      barrier. The authors characterized central nervous system (CNS) disease in these
      women. METHODS: Using pharmacy records, the authors retrospectively identified
      153 women treated with trastuzumab alone or with chemotherapy for HER-2-positive
      metastatic breast carcinoma at Dana-Farber Partners Cancer Care from June 1998 to
      December 2000. A study cohort of 122 patients was identified after excluding
      patients without adequate clinical follow-up or who had CNS disease before
      trastuzumab treatment. Central nervous system disease was defined as one or more
      brain metastases or as leptomeningeal carcinomatosis. The median follow-up of
      this cohort was 23 months. RESULTS: Central nervous system metastases were
      identified in 34% of patients (95% confidence interval, 26-44%) at a median of 16
      months after diagnosis of metastatic breast carcinoma and 6 months from the
      beginning of trastuzumab therapy. Ninety-three percent of patients with CNS
      disease presented with clinical symptoms. Five percent of patients with CNS
      disease had leptomeningeal involvement alone, although 14% had leptomeningeal
      involvement and parenchymal brain metastases. Fifty percent of patients were
      responding or had stable disease while receiving trastuzumab at other disease
      sites at the time of diagnosis of CNS metastasis. The median survival period
      after CNS metastases was 13 months. Fifty percent of patients died of progressive
      CNS disease. Patients receiving trastuzumab as first-line therapy for metastatic
      disease frequently developed brain metastases while responding to or stable on
      trastuzumab at other disease sites. CONCLUSIONS: Metastatic breast carcinoma to
      the CNS is common among patients receiving trastuzumab-based therapy, including
      patients responding to therapy outside the CNS. This may be due either to
      predilection for the CNS by HER-2-positive tumor cells and/or poor penetration of
      the CNS by trastuzumab or to improved visceral disease control leading to a
      longer life and onset of late tumor spread to the CNS. Efforts to characterize
      other risk factors for development of CNS disease, optimal screening algorithms,
      and new treatment strategies may be warranted.

PMID- 12784332
TI  - Elevated expression of cyclooxygenase-2 is a negative prognostic factor for
      disease free survival and overall survival in patients with breast carcinoma.
AB  - BACKGROUND: Cyclooxygenases regulate the production of prostaglandins and play a
      role in tumor development and progression. The authors investigated the
      prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and
      COX-2, on disease-free survival and progression-free survival in patients with
      primary breast carcinoma as well as the association between COX expression and
      other clinicopathologic parameters. METHODS: In this study COX isoform expression
      was determined by immunohistochemistry in a cohort of 221 patients with primary
      breast carcinoma. RESULTS: Expression of COX-2 was detected in 36% of breast
      carcinoma samples and was associated significantly with several clinicopathologic
      parameters, including positive lymph node status (P < 0.0005), larger tumor size
      (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03),
      and negative estrogen receptor status (P = 0.04). In contrast, COX-1 was
      expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02)
      and with negative lymph node status (P = 0.01). In a univariate survival
      analysis, a significant association was observed between elevated COX-2
      expression and decreases in disease-free survival (P = 0.0007) and overall
      survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of
      borderline significance for disease-free survival (relative risk, 1.90; 95%
      confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade,
      number of positive lymph nodes, and patient age. Elevated expression of COX-1 in
      tumor tissue had no statistically significant influence on patient prognosis.
      CONCLUSIONS: The current data suggest that increased expression of COX-2 may play
      a role in the progression of primary breast carcinoma. It remains to be
      investigated whether treatment with selective inhibitors of COX-2 may be an
      additional therapeutic option for patients with breast carcinoma.

PMID- 12784333
TI  - A Phase I/II study of strontium-89 combined with gemcitabine in the treatment of
      patients with androgen independent prostate carcinoma and bone metastases.
AB  - BACKGROUND: The objectives of the current study were to determine the maximum
      tolerated dose and to evaluate the efficacy of gemcitabine given in combination
      with strontium-89 to patients with androgen independent prostate carcinoma.
      METHODS: Patients with androgen-independent prostate carcinoma and painful
      osteoblastic bone metastases were eligible. On a 12-week course, patients
      received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and
      57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8.
      RESULTS: Fifteen patients were registered, and all were assessable for response
      and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600
      mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13
      courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000
      platelets per microL were common at Dose Level 2, and 1 patient had Grade 4
      thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500
      granulocytes per microL occurred in 4 patients at Dose Level 2 and were
      reversible. There were no responses, as measured by prostate specific antigen
      concentration, although 6 patients (40%) had stable disease. CONCLUSIONS: The
      authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for
      the combination. The study was terminated on the basis that an overall response
      rate > than 10% was unlikely. Further study at this dose level and schedule is
      not warranted. .

PMID- 12784334
TI  - Renal cell carcinoma with retroperitoneal lymph nodes. Impact on survival and
      benefits of immunotherapy.
AB  - BACKGROUND: The current study was performed to determine the impact of the
      presence of retroperitoneal lymphadenopathy on the survival and response to
      immunotherapy of patients with metastatic renal cell carcinoma (RCC). METHODS: A
      retrospective cohort study was performed with outcome assessment based on the
      chart review of demographic, clinical, and pathologic data from 1087 patients.
      Patients with RCC who did not present with metastatic disease, who did not
      undergo nephrectomy as part of their cancer treatment, and those in whom either
      the lymph node (N) or metastatic (M) status was unknown, were excluded. A total
      of 322 M1 patients who met these criteria and who underwent nephrectomy for
      unilateral RCC formed the principal study population. RESULTS: Two hundred thirty
      six patients presented with N0M1 disease and 86 patients presented with N+M1
      disease. In M1 patients, the presence of positive regional lymph nodes was
      associated with larger sized, higher grade, locally advanced primary tumors that
      were more commonly associated with sarcomatoid features. N0M1 patients were more
      likely to achieve an objective response to systemic immunotherapy compared with
      N+M1 patients (P = 0.01). N+M1 patients overall had worse short-term and long
      term survival compared with N0M1 patients, with a median survival of 10.5 months
      compared with 20.4 months, respectively. The median survival of N0M1 patients was
      improved to 28 months in those who received adjunctive immunotherapy (P =
      0.0008), whereas the median survival of patients with N+M1 disease was the same
      in those treated with and those treated without adjunctive immunotherapy (P =
      0.18). CONCLUSIONS: Even in the modern era of systemic immunotherapy, the
      presence of regional lymphadenopathy exerts a detrimental effect on the survival
      of patients with metastatic RCC. Lymph node status is a strong predictor of the
      failure to achieve either an objective immunotherapy response or an improvement
      in survival when immunotherapy is given as an adjunctive treatment after
      cytoreductive nephrectomy. However, in multivariate analysis, including both
      clinical and pathologic variables, lymph node status was found to have less of an
      impact on survival than primary tumor stage and grade and patient performance
      status.

PMID- 12784335
TI  - Laparoscopic sentinel lymph node procedure using a combination of patent blue and
      radioisotope in women with cervical carcinoma.
AB  - BACKGROUND: The authors evaluated the feasibility of a laparoscopic sentinel
      lymph node (SN) procedure with combined radioisotopic and patent blue labeling in
      patients with cervical carcinoma. METHODS: Thirteen women (median age, 52.5
      years) with cervical carcinoma (Stage Ia2 in 1 patient, Stage Ib1 in 10 patients,
      Stage Ib2 in 1 patient, and Stage IIa in 1 patient) underwent a laparoscopic SN
      procedure using an endoscopic gamma probe after both radioactive isotope and
      patent blue injections. After the procedure, all patients underwent complete
      laparoscopic pelvic lymphadenectomy and either laparoscopic radical hysterectomy
      (eight patients) or the Schauta-Amreich operation (five patients). RESULTS: SNs
      (mean, 1.7 SNs per patient; range, 1-3 SNs per patient) were identified in 12 of
      13 patients. A median of 10.5 pelvic lymph nodes per patient (range, 4-17 pelvic
      lymph nodes per patient) were removed. No lymph node involvement was detected in
      SNs with hematoxylin and eosin staining. Immunohistochemical studies identified
      four metastatic SNs in two patients, with micrometastases in two SNs from the
      first patient and isolated tumor cells in two SNs from the second patient. No
      false-negative SN results were obtained. CONCLUSIONS: The results of this study
      suggest that SN detection with a combination of radiocolloid and patent blue is
      feasible in patients with cervical carcinoma. The combination of laparoscopy and
      the SN procedure permitted minimally invasive management of early-stage disease.

PMID- 12784336
TI  - Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with
      weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose
      cytosine arabinoside.
AB  - BACKGROUND: To evaluate the activity and toxicity of weekly Schering 54301, a
      polyethylene glycol formulation of interferon- alpha-2b (PEG-IFN-alpha-2b), with
      cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML).
      METHODS: Seventy-six patients with Philadelphia chromosome (Ph)-positive early
      chronic-phase CML were treated with the combination of PEG-IFN-alpha-2b and ara-C
      (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-alpha-2b was 6
      microg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 microg/kg
      in the next 52 patients. RESULTS: Overall, 73% of patients had a complete
      hematologic response, 35% of patients had a major cytogenetic response (Ph <
      35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a
      median follow-up of 19 months, the estimated 2-year survival rate was 89%.
      Therapy was discontinued in 24% of patients due to Grade III-IV toxicity.
      Frequent severe side effects that required dose reductions included neutropenia
      (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-alpha-2b
      and ara-C doses delivered were 3 microg/kg weekly and 7.5 mg daily, respectively,
      at 12 months of therapy. The activity and toxicity profiles of this combination
      was similar to those observed in historical patients treated with IFN-alpha and
      cytarabine. CONCLUSIONS: The combination of PEG-IFN-alpha-2b and ara-C is active
      but has significant toxicity in patients with chronic-phase CML at the dose
      schedule used. The recommended dose of PEG-IFN-alpha-2b in future combination
      studies is 3 microg/kg or less.

PMID- 12784337
TI  - Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular
      carcinoma.
AB  - BACKGROUND: The mitogen-activated protein kinase (MAPK) cascade is activated in
      response to various extracellular stimuli. The authors investigated the
      involvement of the p38 MAPK, a member of the MAPK superfamily, cascade in
      hepatoma cell lines and in human hepatocellular carcinoma (HCC) tissue specimens.
      METHODS: Constitutively active mutant of MAPK kinase 6 (MKK6), which is upstream
      of p38 MAPK, was transfected into the HepG2 and HuH7 human hepatoma cell lines.
      The constitutive active mutant was constructed by replacing Ser-189 and Thr-193
      with Glu. The growth and death of mutant MKK6-transfected hepatoma cells were
      analyzed by the WST-1 and sub-G1 assays. The surgically resected livers of 20 HCC
      patients were divided histologically into tumorous (T) and nontumorous (NT)
      lesions. p38 MAPK activity was analyzed using in vitro kinase assay and MKK6
      activity was measured using Western blot analysis. RESULTS: Mutant MKK6
      transfection increased p38 MAPK activity, cytochrome c release from the
      mitochondria to the cytosol, and caspase-3 activity, accompanied by apoptosis. In
      contrast, SB203580, a p38 MAPK-specific inhibitor, prevented MKK6-induced
      apoptosis in hepatoma cell lines. In the T lesions of 20 HCC parients, p38 MAPK
      and MKK6 activities were significantly lower compared with NT lesions (P < 0.05).
      There was a significant positive correlation between p38 MAPK and MKK6 activity
      (r = 0.507, P < 0.05). Larger tumors (> 20 mm) exhibited lower levels of p38 MAPK
      and MKK6 activity than did smaller tumors (P < 0.05). CONCLUSIONS: These findings
      suggested that reduction of the p38 MAPK cascade may account, in part, for the
      resistance to apoptosis, leading to the unrestricted cell growth of human HCC.

PMID- 12784338
TI  - Percutaneous radiofrequency ablation of liver metastases in potential candidates
      for resection: the "test-of-time approach".
AB  - BACKGROUND: Some surgeons have advocated delaying resection of liver metastases
      to allow additional metastases which may be present, but are undetected, to be
      identified. This "test-of-time" approach can limit the number of resections
      performed on patients who ultimately will develop additional metastases. The
      current study evaluated the potential role and possible advantages of performing
      radiofrequency (RF) ablation during the interval between diagnosis and hepatic
      metastasectomy as part of a test-of-time management approach. METHODS: Eighty
      eight consecutive patients with 134 colorectal carcinoma liver metastases were
      potential candidates for hepatic metastasectomy. They were treated with
      percutaneous RF ablation using single (101 treatments) or triple-probe cluster
      (22 treatments) 18-gauge internally cooled electrodes. Treatment was performed
      under conscious sedation (22 of 119 treatments), anesthesia (14 of 119
      treatments), or general anesthesia (83 of 119 treatments). At the time of the
      initial RF ablation procedure, 49 of 88 patients (56%) were found to have 1
      metastasis, 32 of 88 patients (36%) had 2 metastases, and 7 of 88 patients (8%)
      had 3 metastases. Metastases ranged from 0.6 to 4.0 cm in greatest dimension
      (mean, 2.1 cm). Follow-up with serial computed tomography scans scans ranged from
      18 to 75 months (median, 33 months) after the initial RF ablation. RESULTS: A
      total of 119 RF ablations were performed. Complete necrosis was obtained in 53 of
      88 patients (60%) and in 85 of 134 lesions (63%). During follow-up of these 53
      patients, 16 (30%) remained free of disease and 37 (70%) developed new lesions.
      New lesions were intrahepatic in 26 of 37 patients (70%), extrahepatic in 4
      patients (11%), and both intrahepatic and extrahepatic in 7 patients (19%). Of 26
      patients whose new lesions were intrahepatic only, 15 (58%) were retreated with
      RF and 7 were free of disease at the time of last follow-up (median follow-up, 28
      months). Ten additional patients with only intrahepatic new lesions were deemed
      untreatable and 1 patient underwent resection. Overall, among the 53 patients in
      whom complete tumor necrosis was achieved after RF ablation therapy, 52 (98%)
      were spared surgical resection: 23 (44%) because they have remained free of
      disease and 29 (56%) because they developed disease progression. Among all 88
      patients, 21 (24%) underwent resection after RF ablation (8 were free of disease
      at the time of last follow-up), 23 (26%) remained free of disease after
      successful RF ablation, and 56 (64%) developed untreatable disease progression
      (44 after RF alone, 12 after RF and surgery). Lesions in 35 of 88 patients (40%)
      demonstrated local tumor recurrence on follow-up imaging studies. Twenty of these
      35 patients (57%) underwent surgical resection, whereas the remaining 15 patients
      (43%) developed additional, untreatable metastases. New lesions were intrahepatic
      in 9 of 15 patients (60%), extrahepatic in 1 of 15 patients (7%), and both
      intrahepatic and extrahepatic in 5 of 15 patients (33%). No patient who had been
      treated with RF ablation became unresectable due to the growth of metastases and
      there was no evidence of needle track seeding in any patient after RF ablation.
      Overall, among the 35 patients in whom complete tumor necrosis was not achieved
      after RF ablation therapy, 15 (43%) were spared surgical resection. CONCLUSIONS:
      The results of the current study suggest that current RF ablation techniques,
      when used as part of a test-of-time management approach, can decrease the number
      of resections performed. The approach results in complete tumor necrosis in some
      patients and provide an interval for others who ultimately will develop new
      intrahepatic and/or extrahepatic metastases to do so.

PMID- 12784339
TI  - Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with
      chronic hepatitis C virus infection.
AB  - BACKGROUND: Hepatic steatosis is one of the histopathologic features of chronic
      hepatitis C. It was reported recently that the expression of hepatitis C virus
      (HCV) core protein in transgenic mice induced hepatocellular carcinoma (HCC) in
      association with steatosis. The objective of this study was to determine the
      relation between hepatic steatosis and hepatocarcinogenesis in patients with
      chronic HCV infection. METHODS: The authors studied 161 patients with chronic HCV
      infection who were diagnosed at Nagasaki University Hospital, Nagasaki, Japan,
      between January 1980 and December 1999. Age, gender, body mass index (BMI),
      habitual drinking, diabetes mellitus, serum alanine aminotransferase (ALT) level,
      HCV serotype, serum level of HCV core protein, interferon (IFN) treatment,
      hepatic fibrosis inflammation, and hepatic steatosis were studied with regard to
      their significance in the development of HCC using univariate and multivariate
      analyses. RESULTS: The cumulative incidence rates of HCC were 24%, 51%, and 63%
      at 5 years, 10 years, and 15 years, respectively. Multivariate analysis
      identified hepatic steatosis, together with aging, cirrhosis, and no IFN
      treatment, as independent and significant risk factors for HCC (P = 0.0135, P =
      0.0390, P = 0.0068, and P = 0.0142, respectively). In addition, hepatic steatosis
      was correlated with BMI, serum ALT levels, and triglyceride levels. CONCLUSIONS:
      The findings of the current study indicate that hepatic steatosis is a risk
      factor for HCC in patients with chronic HCV infection. Patients with chronic HCV
      and hepatic steatosis should be monitored carefully for HCC.

PMID- 12784340
TI  - Plasma levels of D-dimer in lung carcinoma: clinical and prognostic significance.
AB  - BACKGROUND: The activation of the clotting-fibrinolytic system in cancer patients
      is common and represents an unfavorable clinical sign. D-dimer (DD) is a
      sensitive marker of fibrinolysis. METHODS: The current study comprised 826 new
      lung carcinoma patients seen consecutively in a single institution over a 10-year
      period (1992-2001). For each patient, 31 variables, including DD and survival
      duration, were available for analysis. RESULTS: Only weak relationships between
      DD and the other variables were found. The DD variable correlated best with the
      level of lactate dehydrogenase, performance status, tissue polypeptide antigen,
      stage of disease, and the number of metastases (rho = 0.33, -0.25, 0.18, 0.18,
      and 0.15, respectively). The D-dimer distinguished patients with different
      prognoses. The median survival periods were 154 days (95% confidence interval
      [CI], 122-189 days) and 308 days (95% CI, 227-409 days; log rank statistic,
      26.56; P < 0.01), respectively, for abnormally elevated and normal values. The
      difference was greater in patients with adenocarcinoma and in patients presenting
      with a less advanced disease, especially in patients with pathologic Stage Ia
      disease. The best multivariate survival model selected 10 significant covariates,
      including DD. CONCLUSIONS: The authors recommend measuring the plasma level of DD
      in all new lung carcinoma patients. This measurement may help to formulate
      individual prognoses and can be used to indicate adjuvant treatment for surgical
      patients.

PMID- 12784341
TI  - Quality-of-life-adjusted survival comparison of sustained-release cytosine
      arabinoside versus intrathecal methotrexate for treatment of solid tumor
      neoplastic meningitis.
AB  - BACKGROUND: The authors compared the quality of life of patients with solid tumor
      neoplastic meningitis treated in a controlled trial that compared conventional
      intrathecal methotrexate with a depot cytosine arabinoside liposomal injection
      (DepoCyt). The authors evaluated the trade-off between toxicity and improved
      clinical outcome. METHODS: Quality-adjusted time without symptoms or toxicity (Q
      TWiST) analysis was used to evaluate data collected prospectively from a
      randomized clinical trial that compared DepoCyt with methotrexate. Sixty-one
      patients with confirmed solid tumor neoplastic meningitis were randomized to
      receive either methotrexate or DepoCyt. RESULTS: Within the 12-month follow-up,
      the average patient in the DepoCyt arm (compared with the methotrexate arm)
      achieved 71 more days of neurologic progression-free survival and 52 more days of
      overall survival, but experienced slightly more days with toxicity. The DepoCyt
      regimen provided greater quality-adjusted survival regardless of the quality-of
      life valuations placed on time with toxicity and time following disease
      progression (range, 44-79 days). This gain was significant (P < 0.05) for all
      patients except for those who placed a high relative value on time following
      disease progression. CONCLUSIONS: The clinical benefits of DepoCyt offset a trend
      toward additional toxicity among patients with sold tumor neoplastic meningitis.
      The magnitude of the benefit depends on how the patient values time spent in
      toxicity and disease progression. The results of this analysis can be used at the
      bedside to make evidence-based individual treatment decisions.

PMID- 12784342
TI  - Nuclear accumulation of basic fibroblast growth factor in human astrocytic
      tumors.
AB  - BACKGROUND: The authors recently reported that nuclear accumulation of basic
      fibroblast growth factor (bFGF) demonstrated a significant correlation with
      recurrence of pituitary adenomas. The current study sought to determine whether
      nuclear bFGF accumulation was a predictor of survival in patients with astrocytic
      tumors. METHODS: The authors examined 52 patients with primary astrocytic tumors.
      Immunohistochemical assays for bFGF, fibroblast growth factor receptor 1 (FGFR1),
      and proliferating cell nuclear antigen were performed. Immunoreactivity of bFGF
      in nuclei was recorded in terms of the bFGF nuclear index (NI), which was
      calculated as the percentage of tumor cells with nuclear immunoreactivity.
      Western blot analysis of bFGF in nuclear fractions was performed. RESULTS: The
      bFGF NI had a mean value of 35.1% and was < 30% (low NI) in 27 patients and >or=
      30% (high NI) in 25 patients. In all cases, FGFR1 immunoreactivity was observed
      in the cytoplasm but not in the nucleus. Western blot analysis indicated that the
      nuclear fractions from tumor specimens with high NI contained high-molecular
      weight bFGF. Univariate analyses showed that age, tumor histology, gender, and
      bFGF NI were significantly correlated with patient survival. Multivariate
      analyses demonstrated that NI had the greatest influence (P = 0.0073) on survival
      rate, compared with age (P = 0.0083) and gender (P = 0.0492). Compared with low
      NI, high NI was associated with a relative risk of 3.292. CONCLUSIONS: The
      findings of the current study suggest that bFGF NI may be a useful predictor of
      survival in patients with astrocytic tumors.

PMID- 12784343
TI  - Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity.
      Histologic response to preoperative chemotherapy correlates with histologic
      subtype of the tumor.
AB  - BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct
      subtypes have been identified, but little is known about the response to
      chemotherapy. METHODS: The authors investigated whether the subtypes correlated
      with histologic response to chemotherapy in 1058 patients with osteosarcoma of
      the extremities who were treated with neoadjuvant chemotherapy over the last 20
      years. The tumors were classified as osteoblastic (70%), chondroblastic (13%),
      fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had
      localized disease and 147 had resectable lung metastases. RESULTS: The response
      to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of
      patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good
      responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and
      telangiectatic (80%) tumors and significantly lower in chondroblastic tumors
      (43%). Prognosis was significantly correlated with the histologic subtypes. The 5
      year overall survival rate was significantly higher (P = 0.0001) in fibroblastic
      (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and
      chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic
      subtype, the 5-year overall survival rate was significantly higher (P = 0.0001)
      in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS:
      The authors concluded that the histologic subtype of primary central high-grade
      osteosarcoma of the extremity was strictly correlated with histologic response to
      chemotherapy and probably, as a consequence, also with prognosis. Further studies
      are needed to establish whether these results justify a specific therapeutic
      approach based on the histologic subtype of the tumor.

PMID- 12784344
TI  - Cancer in the Minnesota Hmong population.
AB  - BACKGROUND: The Hmong are an isolated, agrarian people who settled in the
      mountainous regions of what today are Vietnam, Cambodia, and Laos. After the
      Vietnam War, many Hmong were relocated to the U.S. Minnesota has the second
      largest population (after California) of Hmong individuals. The objective of this
      study was to examine cancer incidence in this population, because it may indicate
      areas for targeted surveillance and intervention. METHODS: The Minnesota Cancer
      Surveillance System database was screened for Hmong surnames, and proportional
      incidence ratios (PIRs) were calculated for the period 1988-1999. RESULTS:
      Compared with all Minnesotans, the Hmong population had increased PIRs for
      nasopharyngeal cancer (PIR, 39.39; 95% confidence interval [95% CI], 21.01
      66.86), gastric cancer (PIR, 8.70; 95% CI, 5.39-13.25), hepatic cancer (PIR,
      8.08; 95% CI, 3.88-14.71), and cervical cancer (PIR, 3.72; 95% CI, 2.04-6.20) and
      had decreased PIRs for prostate cancer, breast cancer, Hodgkin disease, and
      melanoma. CONCLUSIONS: The current observations have implications for cancer
      control interventions. In particular, an increased incidence of cervical cancer
      might be addressed in part by targeting culturally sensitive screening programs
      in the Hmong population.

PMID- 12784345
TI  - Cancer incidence in the US radiologic technologists health study, 1983-1998.
AB  - BACKGROUND: Workers exposed to low doses of radiation can provide information
      regarding cancer risks that are of public concern. However, characterizing risk
      at low doses requires large populations and ideally should include a large
      proportion of women, both of which rarely are available. METHODS: Among 90305
      radiologic technologists in the U.S. (77% women) who were followed during 1983
      1998, data concerning incident cancer occurrence was obtained from mailed
      questionnaires and from death records. Standardized incidence ratios (SIRs) were
      computed using age-specific, gender-specific, race-specific, and calendar year
      specific cancer rates from the Surveillance, Epidemiology, and End Results
      Program. RESULTS: The SIR for all cancers in both genders combined was 1.04 (95%
      confidence interval [95% CI], 1.00-1.07; n = 3292 technologists). Female
      technologists had an elevated risk for all solid tumors combined (SIR = 1.06; 95%
      CI, 1.02-1.10; n = 2168 women) and for breast cancers (SIR = 1.16; 95% CI, 1.09
      1.23; n = 970 women), melanoma (SIR = 1.66; 95% CI, 1.43-1.89; n = 181 women),
      and thyroid cancers (SIR = 1.54; 95% CI, 1.24-1.83; n = 107 women). Male
      technologists experienced a decreased risk for solid tumors (SIR = 0.92; 95% CI,
      0.85-0.98; n = 755 men); however, melanoma (SIR = 1.39; 95% CI, 1.00-1.79; n = 56
      men) and thyroid cancers (SIR = 2.23; 95% CI, 1.29-3.59; n = 17 men) were
      increased. Among both genders, the risks were decreased for buccal
      cavity/pharyngeal cancers (SIR = 0.73; 95% CI, 0.55-0.90; n = 54 technologists),
      rectal cancers (SIR = 0.62; 95% CI 0.48-0.76; n = 53 technologists), and lung
      cancers (SIR = 0.77, 95% CI, 0.70-0.85; n = 307 technologists). CONCLUSIONS: The
      elevated risk for breast cancer may have been related to occupational radiation
      exposure. The observed excesses of melanoma and thyroid cancers may reflect, at
      least in part, earlier detection among medical workers with easy access to health
      care.

PMID- 12784347
TI  - Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin-11) for
      secondary prophylaxis of thrombocytopenia in solid tumor patients receiving
      chemotherapy.
AB  - BACKGROUND: Previous research has shown oprelvekin (recombinant human interleukin
      11 [rhIL-11]) to be effective in reducing the requirements for platelet
      transfusions after myelosuppressive chemotherapy in patients who have previously
      experienced thrombocytopenia. The economic consequences of the routine use of
      this platelet growth factor and the usual standard of platelet transfusions for
      prophylaxis of severe chemotherapy-induced thrombocytopenia have not been
      compared. METHODS: The authors constructed a decision-analytic model to compare
      the alternatives of rhIL-11 versus usual care using probability, outcome, and
      cost data from previously published clinical trials and their own institutional
      sources. They incorporated the costs of platelet transfusions and adverse events
      from rhIL-11 into the analysis. Quality-of-life outcomes were not considered. The
      pharmacoeconomic analysis was based on the criterion of cost minimization from
      the payer's perspective. RESULTS: The expected cost of the usual care strategy
      for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20000
      microL(-1)) was US dollars 3495 for a 3-week cycle of chemotherapy. The
      prophylactic rhIL-11 strategy was more expensive, with an expected cost of US
      dollars 5328 over the same time period. Nonetheless, it was associated with fewer
      platelet transfusions, avoiding an average of 6.7 U compared with usual care. The
      savings from avoidance of platelet transfusion and adverse reactions to
      transfusion from the use of rhIL-11 were not offset by the substantial cost of
      the pharmaceutical. The greater expected costs from the rhIL-11 strategy were
      relatively insensitive to the unit price and efficacy of rhIL-11 and the costs of
      platelet transfusions and monitoring. CONCLUSIONS: From the payer's perspective,
      rhIL-11 cannot be considered a cost-saving clinical strategy compared with
      routine platelet transfusions for patients with severe chemotherapy-induced
      thrombocytopenia.

PMID- 12784346
TI  - Addition of the neurokinin 1 receptor antagonist aprepitant to standard
      antiemetic therapy improves control of chemotherapy-induced nausea and vomiting.
      Results from a randomized, double-blind, placebo-controlled trial in Latin
      America.
AB  - BACKGROUND: Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been
      shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when
      added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus
      a corticosteroid. The authors sought to evaluate further the efficacy and
      tolerability of aprepitant plus standard therapy in a large clinical trial.
      METHODS: This was a multicenter, randomized, double-blind, placebo-controlled,
      parallel-groups, Phase III study. Patients with cancer who were scheduled to
      receive treatment with high-dose cisplatin chemotherapy were randomized to
      receive 1 of 2 treatment regimens; the standard therapy group received
      intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral
      dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral
      aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on
      Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3;
      and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use
      of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat
      approach was used to analyze the efficacy data. The primary endpoint was complete
      response (no emesis and no rescue therapy) during the 5-day period postcisplatin.
      Treatment comparisons were made using logistic regression models, and reported
      adverse events and physical and laboratory assessments were used to assess
      tolerability. RESULTS: A total of 523 patients were evaluated for efficacy, and
      568 patients were evaluated for safety. During the 5 days after chemotherapy, the
      percentages of patients who achieved a complete response were 62.7% in the
      aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group
      (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were
      82.8% for the aprepitant group and 68.4% for the standard therapy group (P <
      0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant
      group and 46.8% in the standard therapy group (P < 0.001). The overall incidence
      of adverse events was similar between the 2 treatment groups (72.8% in the
      aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group
      [207 of 285 patients]) as were rates of serious adverse events, discontinuations
      due to adverse events, and deaths. CONCLUSIONS: In patients with cancer who are
      receiving high-dose cisplatin-based chemotherapy, therapy consisting of
      aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of
      ondansetron and dexamethasone provided superior antiemetic protection compared
      with standard therapy alone and was generally well tolerated.

PMID- 12784348
TI  - Hepatic focal nodular hyperplasia in children previously treated for a solid
      tumor. Incidence, risk factors, and outcome.
AB  - BACKGROUND: The detection of hepatic nodules, particularly in patients treated
      for a previous malignancy, raises a diagnostic dilemma. Focal nodular hyperplasia
      (FNH) of the liver is an uncommon, benign tumor in children and must be
      differentiated from malignant hepatic lesions. The etiology of FNH is obscure,
      and its pathogenesis is poorly understood. FNH may be a reaction to localized
      vascular abnormalities and circulatory disturbances. The goal of the current
      study was to identify risk factors for the occurrence of FNH in children who had
      received prior treatment for a malignant tumor. METHODS: The current
      retrospective study examined 14 cases of FNH in pediatric patients who previously
      had been treated for a malignancy. Diagnosis was based on clinical and radiologic
      findings and was proven histologically in four cases. RESULTS: FNH lesions were
      discovered by chance during routine examination in 78% of patients. The incidence
      of FNH was particularly high in the current series (0.45%) compared with the
      incidence in the general pediatric population. High doses of alkylating agents
      (e.g., busulfan or melphalan), venoocclusive disease, and liver radiotherapy may
      be responsible for injury to the vascular endothelium and subsequent localized
      circulatory disturbances. FNH is characterized by the absence of complications
      after its detection; therefore, only close follow-up is recommended. CONCLUSIONS:
      FNH appears to be a late complication of an iatrogenic vascular disease in
      children with a history of malignancy.

PMID- 12784349
TI  - Measurement of serum squamous cell carcinoma antigen levels as a predictor of
      radiation response in patients with carcinoma of the uterine cervix.
AB  - BACKGROUND: Optimal timing of the measurement of serum squamous cell carcinoma
      (SCC) antigen during radiation therapy (RT) and its significance for predicting
      the response of cervical carcinoma patients as early as possible remain unknown.
      METHODS: Sixty-three patients with SCC of the uterine cervix who received RT only
      were studied. Patients were treated with a combination of external beam
      irradiation and high-dose rate intracavitary irradiation. The serum SCC antigen
      level was measured before, every 2 or 3 weeks during, and 1 or 2 months after RT.
      Clinical outcome was divided into complete response and incomplete response.
      RESULTS: Forty-seven patients (74.6%) had serum SCC antigen levels 1.5 ng/mL (the
      reference value) before RT. Normalization of serum SCC antigen levels at the end
      of RT were found to be significantly correlated with complete response in the SCC
      positive patients. It was especially noted that in patients with serum SCC levels
      between 5-30 ng/mL before RT, a > 70% decrease in the serum SCC antigen level at
      4 weeks was correlated significantly with complete response. In this group, a
      significant correlation also was found between a > 70% decrease in serum SCC
      level at 4 weeks and the normalization of SCC at the end of RT. CONCLUSIONS: The
      current study data suggest that the serum SCC antigen level not only before, but
      also during and at the end of RT can predict the response of patients with
      cervical carcinoma and help in identifying those patients who are at high risk of
      local recurrence and/or distant metastasis.

PMID- 12784350
TI  - A safe and effective method for converting patients from transdermal to
      intravenous fentanyl for the treatment of acute cancer-related pain.
AB  - BACKGROUND: The delayed effects (12-16 hours) of transdermal fentanyl make dose
      titration difficult during acute exacerbations of cancer pain. Patients at the
      authors' institution routinely are switched from transdermal to intravenous (IV)
      fentanyl using a 1:1 (transdermal:IV) conversion during severe episodes of pain.
      METHODS: The authors evaluated nine consecutive hospitalized patients with cancer
      who had severe pain for up to 6 days following the conversion from transdermal to
      IV fentanyl. Pain intensity was rated using an 11-point (0-10) verbal numeric
      rating scale (NRS). All 9 patients initially reported their pain intensity with
      movement as >or= 8 during treatment with transdermal fentanyl. Eight patients
      initially reported their pain at rest as >or= 8. In each patient, all transdermal
      patches were removed, and a continuous infusion (CI) delivering IV fentanyl at
      the same hourly rate was initiated simultaneously. Demand boluses of IV fentanyl
      equivalent in dosage to 50-100% of the CI rate remained available by patient
      controlled analgesia (PCA). Pain intensity (0-10), sedation (0-3), and hourly
      fentanyl requirements (micrograms per hour) were assessed and recorded
      immediately prior to patch removal and at least once daily after the initiation
      of IV fentanyl. The CI and demand boluses were titrated whenever necessary on the
      basis of pain intensity and supplemental PCA use. RESULTS: All 9 patients
      reported mild levels (<or= 4) of pain at rest within 5 days. The median time to
      achieve mild levels of pain at rest was 1.5 days. Six patients achieved mild
      levels of pain with movement within 3 days. Three patients never achieved mild
      levels of pain with movement while receiving IV fentanyl. No serious side effects
      were reported. CONCLUSIONS: The conversion from transdermal to IV fentanyl can be
      accomplished safely and effectively using a 1:1 (transdermal:IV) conversion
      during acute exacerbations of cancer pain.

PMID- 12784351
TI  - Relationship between changes in hemoglobin level and quality of life during
      chemotherapy in anemic cancer patients receiving epoetin alfa therapy.

PMID- 12784353
TI  - Predictive factors for suicidal ideation in patients with unresectable lung
      carcinoma. A 6-month follow-up study.

PMID- 12784359
TI  - CAPRI: a Critical Assessment of PRedicted Interactions.
AB  - CAPRI is a communitywide experiment to assess the capacity of protein-docking
      methods to predict protein-protein interactions. Nineteen groups participated in
      rounds 1 and 2 of CAPRI and submitted blind structure predictions for seven
      protein-protein complexes based on the known structure of the component proteins.
      The predictions were compared to the unpublished X-ray structures of the
      complexes. We describe here the motivations for launching CAPRI, the rules that
      we applied to select targets and run the experiment, and some conclusions that
      can already be drawn. The results stress the need for new scoring functions and
      for methods handling the conformation changes that were observed in some of the
      target systems. CAPRI has already been a powerful drive for the community of
      computational biologists who development docking algorithms. We hope that this
      issue of Proteins will also be of interest to the community of structural
      biologists, which we call upon to provide new targets for future rounds of CAPRI,
      and to all molecular biologists who view protein-protein recognition as an
      essential process.

PMID- 12784360
TI  - GAPDOCK: a Genetic Algorithm Approach to Protein Docking in CAPRI round 1.
AB  - As part of the first Critical Assessment of PRotein Interactions, round 1, we
      predict the structure of two protein-protein complexes, by using a genetic
      algorithm, GAPDOCK, in combination with surface complementarity, buried surface
      area, biochemical information, and human intervention. Among the five models
      submitted for target 1, HPr phosphocarrier protein (B. subtilis) and the
      hexameric HPr kinase (L. lactis), the best correctly predicts 17 of 52
      interprotein contacts, whereas for target 2, bovine rotavirus VP6 protein
      monoclonal antibody, the best model predicts 27 of 52 correct contacts. Given the
      difficult nature of the targets, these predictions are very encouraging and
      compare well with those obtained by other methods. Nevertheless, it is clear that
      there is a need for improved methods for distinguishing between "correct" and
      "plausible but incorrect" complexes.

PMID- 12784361
TI  - Evaluation of the third solvent clusters fitting procedure for the prediction of
      protein-protein interactions based on the results at the CAPRI blind docking
      study.
AB  - To predict protein-protein interactions, rough or coarse handling for the induced
      fit problem is proposed. Our method involves the overlap of two hydrophobic
      interactions as "third solvent clusters fitting." Predictions for binding sites
      and geometric centers were acceptable, but those of the binding axes were poor.
      In this study, only the largest benzene cluster was used for the third solvent
      clusters fitting. For the next CAPRI targets, we must perform protein-protein
      interaction analyses, which include other smaller benzene clusters.

PMID- 12784362
TI  - Modeling protein complexes with BiGGER.
AB  - This article describes the method and results of our participation in the
      Critical Assessment of PRediction of Interactions (CAPRI) experiment, using the
      protein docking program BiGGER (Bimolecular complex Generation with Global
      Evaluation and Ranking) (Palma et al., Proteins 2000;39:372-384). Of five target
      complexes (CAPRI targets 2, 4, 5, 6, and 7), only one was successfully predicted
      (target 6), but BiGGER generated reasonable models for targets 4, 5, and 7, which
      could have been identified if additional biochemical information had been
      available.

PMID- 12784363
TI  - Weighted geometric docking: incorporating external information in the rotation
      translation scan.
AB  - Weighted geometric docking is a prediction algorithm that matches weighted
      molecular surfaces. Each molecule is represented by a grid of complex numbers,
      storing information about the shape of the molecule in the real part and weight
      information in the imaginary part. The weights are based on experimental
      biochemical and biophysical data or on theoretical analyses of amino acid
      conservation or correlation patterns in multiple-sequence alignments of
      homologous proteins. Only a few surface residues on either one or both molecules
      are weighted. In contrast to methods that use postscan filtering based on
      biochemical information, our method incorporates the external data in the
      rotation-translation search, producing a different set of docking solutions
      biased toward solutions in which the up-weighted residues are at the interface.
      Similarly, interactions involving specified residues can be impeded. The weighted
      geometric algorithm was applied to five systems for which regular geometric
      docking of the unbound molecules gave poor results. We obtained much better
      ranking of the nearly correct prediction and higher statistical significance when
      weighted geometric docking was used. The method was successful even when the
      weighted portion of the surface corresponded only partially and approximately to
      the binding site.

PMID- 12784364
TI  - Guided docking: first step to locate potential binding sites.
AB  - The long-range electrostatic forces of the targets in round 2 of the Critical
      Assessment of PRediction of Interactions (CAPRI) experiment were examined and a
      simple guided docking method, based on these forces, was applied. The method
      described consists of calculating an initial rigid body trajectory and an
      optional final, fully flexible refinement stage. Although only limited success
      was found in predicting the final complexes, some interesting information was
      discovered. In particular, the long-range forces seem to give some insight into
      the unusual binding mode of target 4 while raising some questions about target 7,
      which warrant further investigation.

PMID- 12784365
TI  - Finding needles in haystacks: Reranking DOT results by using shape
      complementarity, cluster analysis, and biological information.
AB  - We present an evaluation of our results for the first Critical Assessment of
      PRedicted Interaction (CAPRI). The methods used include the molecular docking
      program DOT, shape analysis tool FADE, cluster analysis and filtering based on
      biological data. Good results were obtained for most of the seven CAPRI targets,
      and for two systems, submissions having the highest number of correctly predicted
      contacts were produced.

PMID- 12784366
TI  - Prediction of the unknown: inspiring experience with the CAPRI experiment.
AB  - We submitted predictions for all seven targets in the CAPRI experiment. For four
      targets, our submitted models included acceptable, medium accuracy predictions of
      the structures of the complexes, and for a fifth target we identified the
      location of the binding site of one of the molecules. We used a weighted
      geometric docking algorithm in which contacts involving specified parts of the
      surfaces of either one or both molecules were up-weighted or down-weighted. The
      weights were based on available structural and biochemical data or on sequence
      analyses. The weighted-geometric docking proved very useful for five targets,
      improving the complementarity scores and the ranks of the nearly correct
      solutions, as well as their statistical significance. In addition, the weighted
      geometric docking promoted formation of clusters of similar solutions, which
      include more accurate predictions.

PMID- 12784367
TI  - A soft docking algorithm for predicting the structure of antibody-antigen
      complexes.
AB  - An efficient soft docking algorithm is described for predicting the mode of
      binding between an antibody and its antigen based on the three-dimensional
      structures of the molecules. The basic tools are the "simplified protein" model
      and the docking algorithm of Wodak and Janin. The side-chain flexibility of Arg,
      Lys, Asp, Glu, and Met residues on the protein surface is taken into account. A
      combined filtering technique is used to select candidate binding modes. After
      energy minimization, we calculate a scoring function, which includes
      electrostatic and desolvation energy terms. This procedure was applied to targets
      04, 05, and 06 of CAPRI, which are complexes of three different camelid antibody
      VHH variable domains with pig alpha-amylase. For target 06, two native-like
      structures with a root-mean-square deviation < 4.0 A relative to the X-ray
      structure were found within the five top ranking structures. For targets 04 and
      05, our procedure produced models where more than half of the antigen residues
      forming the epitope were correctly predicted, albeit with a wrong VHH domain
      orientation. Thus, our soft docking algorithm is a promising tool for predicting
      antibody-antigen recognition.

PMID- 12784368
TI  - Assessment of blind predictions of protein-protein interactions: current status
      of docking methods.
AB  - The current status of docking procedures for predicting protein-protein
      interactions starting from their three-dimensional structure is assessed from a
      first major evaluation of blind predictions. This evaluation was performed as
      part of a communitywide experiment on Critical Assessment of PRedicted
      Interactions (CAPRI). Seven newly determined structures of protein-protein
      complexes were available as targets for this experiment. These were the complexes
      between a kinase and its protein substrate, between a T-cell receptor beta-chain
      and a superantigen, and five antigen-antibody complexes. For each target, the
      predictors were given the experimental structures of the free components, or of
      one free and one bound component in a random orientation. The structure of the
      complex was revealed only at the time of the evaluation. A total of 465
      predictions submitted by 19 groups were evaluated. These groups used a wide range
      of algorithms and scoring functions, some of which were completely novel. The
      quality of the predicted interactions was evaluated by comparing residue-residue
      contacts and interface residues to those in the X-ray structures and by analyzing
      the fit of the ligand molecules (the smaller of the two proteins in the complex)
      or of interface residues only, in the predicted versus target complexes. A total
      of 14 groups produced predictions, ranking from acceptable to highly accurate for
      five of the seven targets. The use of available biochemical and biological
      information, and in one instance structural information, played a key role in
      achieving this result. It was essential for identifying the native binding modes
      for the five correctly predicted targets, including the kinase-substrate complex
      where the enzyme changes conformation on association. But it was also the cause
      for missing the correct solution for the two remaining unpredicted targets, which
      involve unexpected antigen-antibody binding modes. Overall, this analysis reveals
      genuine progress in docking procedures but also illustrates the remaining serious
      limitations and points out the need for better scoring functions and more
      effective ways for handling conformational flexibility.

PMID- 12784369
TI  - ZDOCK predictions for the CAPRI challenge.
AB  - The CAPRI Challenge is a blind test of protein-protein-docking algorithms that
      predict the complex structure from the crystal structures of the interacting
      proteins. We participated in both rounds of this blind test and submitted
      predictions for all seven targets, relying mainly on our Fast Fourier Transform
      based algorithm ZDOCK that combines shape complementarity, desolvation, and
      electrostatics. Our group made good predictions for three targets and had at
      least some success with three others. Implications of the treatment of prior
      biological information as well as contributions of manual inspection to docking
      predictions are also discussed.

PMID- 12784370
TI  - Evaluation of the 3D-Dock protein docking suite in rounds 1 and 2 of the CAPRI
      blind trial.
AB  - The 3D-Dock suite of programs has been used to make predictions for the seven
      targets in rounds 1 and 2 of the CAPRI method evaluation exercise. Some correct
      contacts were obtained in at least one prediction for four of seven targets.
      Target 06 was predicted very well, with an RMSD of the ligand after
      superimposition of the receptor of only 0.77 A. We investigate the performance of
      the various stages of the method, with the aim of finding where improvements need
      to be made, and in particular whether the manual interventions that were made
      were essential, and whether results of the level of accuracy obtained for target
      06 may be expected with confidence.

PMID- 12784371
TI  - ZDOCK: an initial-stage protein-docking algorithm.
AB  - The development of scoring functions is of great importance to protein docking.
      Here we present a new scoring function for the initial stage of unbound docking.
      It combines our recently developed pairwise shape complementarity with
      desolvation and electrostatics. We compare this scoring function with three other
      functions on a large benchmark of 49 nonredundant test cases and show its
      superior performance, especially for the antibody-antigen category of test cases.
      For 44 test cases (90% of the benchmark), we can retain at least one near-native
      structure within the top 2000 predictions at the 6 degrees rotational sampling
      density, with an average of 52 near-native structures per test case. The
      remaining five difficult test cases can be explained by a combination of poor
      binding affinity, large backbone conformational changes, and our algorithm's
      strong tendency for identifying large concave binding pockets. All four scoring
      functions have been integrated into our Fast Fourier Transform based docking
      algorithm ZDOCK, which is freely available to academic users at
      http://zlab.bu.edu/~ rong/dock.

PMID- 12784372
TI  - A protein-protein docking benchmark.
AB  - We have developed a nonredundant benchmark for testing protein-protein docking
      algorithms. Currently it contains 59 test cases: 22 enzyme-inhibitor complexes,
      19 antibody-antigen complexes, 11 other complexes, and 7 difficult test cases.
      Thirty-one of the test cases, for which the unbound structures of both the
      receptor and ligand are available, are classified as follows: 16 enzyme
      inhibitor, 5 antibody-antigen, 5 others, and 5 difficult. Such a centralized
      resource should benefit the docking community not only as a large curated test
      set but also as a common ground for comparing different algorithms. The benchmark
      is available at (http://zlab.bu.edu/~rong/dock/benchmark.shtml).

PMID- 12784373
TI  - Successful discrimination of protein interactions.
AB  - We present results from the prediction of protein complexes associated with the
      first Critical Assessment of PRediction of Interactions (CAPRI) experiment. Our
      algorithm, SmoothDock, comprises four steps: (1) we perform rigid body docking
      using the program DOT, keeping the top 20,000 structures as ranked by surface
      complementarity; (2) we rerank these structures according to a free energy
      estimate that includes both desolvation and electrostatics and retain the top
      2000 complexes; (3) we cluster the filtered complexes using a pairwise root-mean
      square deviation (RMSD) criterion; (4) the 25 largest clusters are subject to a
      smooth docking discrimination algorithm where van der Waals forces are taken into
      account. We predicted targets 1, 6, and 7 with RMSDs of 9.5, 2.4, and 2.6 A,
      respectively. More importantly, from the perspective of biological applications,
      our approach consistently ranked the correct model first (i.e., with highest
      confidence). For target 5 we identified the binding region but not the correct
      orientation. Although we were able to find reasonable clusters for all targets,
      low-affinity complexes (K(d) < nM) were harder to discriminate. For four of seven
      targets, the top models predicted by our automated procedure were among the best
      communitywide predictions.

PMID- 12784374
TI  - Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2.
AB  - This article describes and reviews our efforts using Hex 3.1 to predict the
      docking modes of the seven target protein-protein complexes presented in the
      CAPRI (Critical Assessment of Predicted Interactions) blind docking trial. For
      each target, the structure of at least one of the docking partners was given in
      its unbound form, and several of the targets involved large multimeric structures
      (e.g., Lactobacillus HPr kinase, hemagglutinin, bovine rotavirus VP6). Here we
      describe several enhancements to our original spherical polar Fourier docking
      correlation algorithm. For example, a novel surface sphere smothering algorithm
      is introduced to generate multiple local coordinate systems around the surface of
      a large receptor molecule, which may be used to define a small number of initial
      ligand-docking orientations distributed over the receptor surface. High
      resolution spherical polar docking correlations are performed over the resulting
      receptor surface patches, and candidate docking solutions are refined by using a
      novel soft molecular mechanics energy minimization procedure. Overall, this
      approach identified two good solutions at rank 5 or less for two of the seven
      CAPRI complexes. Subsequent analysis of our results shows that Hex 3.1 is able to
      place good solutions within a list of <or=20 for four of the seven targets. This
      finding shows that useful in silico protein-protein docking predictions can now
      be made with increasing confidence, even for very large macromolecular complexes.

PMID- 12784375
TI  - Taking geometry to its edge: fast unbound rigid (and hinge-bent) docking.
AB  - We present a very efficient rigid "unbound" soft docking methodology, which is
      based on detection of geometric shape complementarity, allowing liberal steric
      clash at the interface. The method is based on local shape feature matching,
      avoiding the exhaustive search of the 6D transformation space. Our experiments at
      CAPRI rounds 1 and 2 show that although the method does not perform an exhaustive
      search of the 6D transformation space, the "correct" solution is never lost.
      However, such a solution might rank low for large proteins, because there are
      alternatives with significantly larger geometrically compatible interfaces. In
      many cases this problem can be resolved by successful a priori focusing on the
      vicinity of potential binding sites as well as the extension of the technique to
      flexible (hinge-bent) docking. This is demonstrated in the experiments performed
      as a lesson from our CAPRI experience.

PMID- 12784376
TI  - ICM-DISCO docking by global energy optimization with fully flexible side-chains.
AB  - The ICM-DISCO (Docking and Interface Side-Chain Optimization) protein-protein
      docking method is a direct stochastic global energy optimization from multiple
      starting positions of the ligand. The first step is performed by docking of a
      rigid all-atom ligand molecule to a set of soft receptor potentials precalculated
      on a 0.5 A grid from realistic solvent-corrected force-field energies. This step
      finds the correct solution as the lowest energy conformation in almost 100% of
      the cases in which interfaces do not change on binding. The second step is needed
      to deal with the induced changes and includes the global optimization of the
      interface side-chains of up to 400 best solutions. The CAPRI predictions were
      performed fully automatically with this method. Available experimental
      information was included as a filtering step to favor expected docking surfaces.
      In three of the seven proposed targets, the ICM-DISCO method found a good
      solution (>50% of correct contacts) within the five submitted models. The
      procedure is global and fully automated. We demonstrate that the algorithm
      handles the induced changes of surface side-chains but is less successful if the
      backbone undergoes large-scale rearrangements.

PMID- 12784377
TI  - Protein-protein docking predictions for the CAPRI experiment.
AB  - We predicted structures for all seven targets in the CAPRI experiment using a new
      method in development at the time of the challenge. The technique includes a low
      resolution rigid body Monte Carlo search followed by high-resolution refinement
      with side-chain conformational changes and rigid body minimization. Decoys
      (approximately 10(6) per target) were discriminated using a scoring function
      including van der Waals and solvation interactions, hydrogen bonding, residue
      residue pair statistics, and rotamer probabilities. Decoys were ranked,
      clustered, manually inspected, and selected. The top ranked model for target 6
      predicted the experimental structure to 1.5 A RMSD and included 48 of 65 correct
      residue-residue contacts. Target 7 was predicted at 5.3 A RMSD with 22 of 37
      correct residue-residue contacts using a homology model from a known complex
      structure. Using a preliminary version of the protocol in round 1, target 1 was
      predicted within 8.8 A although few contacts were correct. For targets 2 and 3,
      the interface locations and a small fraction of the contacts were correctly
      identified.

PMID- 12784378
TI  - Tumor necrosis factor inhibitors "SPARCC" an interest in consensus.

PMID- 12784379
TI  - Patient self-management in arthritis? Yes!

PMID- 12784380
TI  - Patient self-management in arthritis? Yes, more research!

PMID- 12784381
TI  - Results from controlled clinical trials: how relevant for clinical practice?

PMID- 12784382
TI  - Most patients receiving routine care for rheumatoid arthritis in 2001 did not
      meet inclusion criteria for most recent clinical trials or american college of
      rheumatology criteria for remission.
AB  - OBJECTIVE: To determine the proportion of 2 cohorts of patients with rheumatoid
      arthritis (RA) in Nashville, Tennessee, who met 4 common criteria for inclusion
      in clinical trials: > or = 6 swollen joints, > or = 6 tender joints, erythrocyte
      sedimentation rate > or = 28 mm/h, and/or morning stiffness > or = 45 min.
      METHODS: Two cohorts of patients with RA, all of whom had met American Rheumatism
      Association (ARA) [now American College of Rheumatology (ACR)] criteria for RA at
      some time, were studied. Cohort L (late) included 146 consecutive patients whose
      mean disease duration was 14.0 years and who had been under care at a weekly
      academic rheumatology clinic for a mean of 6.2 years when seen in 1998-2001.
      Cohort E (early) included 232 patients of 5 private practice rheumatologists
      whose symptoms began in 1998 or later and whose mean disease duration was 1.8
      years when seen in 2001. Patients were reviewed for the 4 inclusion criteria as
      well as 6 ARA remission criteria. RESULTS: In Cohort L, on a 28 joint count,
      42.5% of patients had > or = 6 swollen joints, 25.3% had > or = 6 tender joints,
      19.9% had both > or = 6 swollen and > or = 6 tender joints, 25.0% had ESR > or =
      28, and 45.9% had morning stiffness > or = 45 min. In Cohort E, on a 42 joint
      count, 63.4% of patients had > or = 6 swollen joints, 50.4% had > or = 6 tender
      joints, 38.8% had both > or = 6 swollen and > or = 6 tender joints, 49.3% had ESR
      > or = 28, and 50.9% had morning stiffness > or = 45 min. Overall, 15.3% of
      Cohort L and 34.1% of Cohort E patients had > or = 6 swollen and tender joints,
      as well as an ESR > or = 28 or morning stiffness > or = 45 min. Only 4.1% of
      Cohort L and no patient in Cohort E met ARA criteria for remission. CONCLUSION:
      The majority of patients seen in routine care in these 2 cohorts did not meet
      criteria for inclusion in most contemporary RA clinical trials, including
      clinical trials sponsored by pharmaceutical companies to introduce new drugs or
      biological agents. Few of these patients met ARA criteria for remission.
      Controlled trial data are not available concerning results of treatment with new
      biological agents or disease modifying antirheumatic drugs in a large proportion,
      if not a majority, of patients with RA at this time.

PMID- 12784383
TI  - Identification of self-epitopes recognized by T cells in rheumatoid arthritis
      demonstrates matrix metalloproteinases as a novel T cell target.
AB  - OBJECTIVE: To identify novel arthritis-associated and/or cartilage-specific self
      epitopes recognized by T cells in patients with rheumatoid arthritis (RA).
      METHODS: Human analogs of several self-epitopes recognized in the rat adjuvant
      arthritis (AA) model (n = 13) were tested for T cell recognition in patients with
      RA and healthy controls. Recognition was assessed by proliferative activity of
      peripheral blood mononuclear cells (PBMC). In addition, cytokine production was
      determined. RESULTS: Six out of the 13 peptides recognized during AA were also
      recognized by more than 20% of the RA patients, in contrast to only one out of
      the 16 control peptides that were not recognized during AA. The highest
      proliferative responses were to matrix metalloproteinase (MMP)-derived peptides.
      The response to a MMP-1 epitope was significantly higher in RA patients than in
      healthy controls. Moreover, this MMP-1 epitope increased interleukin 4 (IL-4)
      production of RA PBMC and decreased IL-4 production by control PBMC. The
      proliferative response to a MMP-3 epitope was similar in RA patients and
      controls; however, the MMP-3 epitope increased IL-4, and concomitantly IL-1beta
      and tumor necrosis factor-a production of RA PBMC, whereas these cytokines were
      unaffected in control PBMC. CONCLUSION: This study shows the presence of immune
      reactions to MMP-derived T cell epitopes that are associated with RA, suggesting
      a novel role of MMP in RA.

PMID- 12784384
TI  - Expression and function of the co-stimulator H4/ICOS on activated T cells of
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the expression and function of the inducible co
      stimulator H4/ICOS in rheumatoid arthritis (RA) patients. H4/ICOS is the newest
      member of the CD28/CTLA-4 family to have been found to be expressed on activated
      T cells, and it participates in a variety of important immunoregulatory
      functions. METHODS: The levels of H4/ICOS expression on T cells among peripheral
      blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from
      28 patients with RA were analyzed by flow cytometry. To explore the role of
      H4/ICOS function in the inflammation of rheumatoid joints, lymphokine production
      by SF CD4+ T cells co-stimulated by H4/ICOS was assayed. Expression of H4/ICOS
      ligand (B7RP-1) mRNA in synovial tissues from patients with RA was examined by
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: H4/ICOS
      positive cells were increased significantly in whole, CD4+, and CD8+ T-cell
      fractions of SFMC compared with control PBMC. Comparison between control PB and
      PB from patients with active RA showed that H4/ICOS-positive whole and CD8+ T
      cell fractions were increased significantly in the PB of RA patients. H4/ICOS
      costimulation clearly increased interferon-g, interleukin 4 (IL-4), and IL-10
      production by SF CD4+ T cells. By RT-PCR, RA synovial tissue was shown to express
      mRNA of B7RP-1. CONCLUSION: Our results suggest that local immune responses may
      be modulated by H4/ICOS expressed on T cells in the joints of patients with RA,
      and thus H4/ICOS may be involved in the pathogenetic mechanism of RA.

PMID- 12784385
TI  - Hyaluronan inhibits matrix metalloproteinase-1 production by rheumatoid synovial
      fibroblasts stimulated by proinflammatory cytokines.
AB  - OBJECTIVE: To study the inhibitory effects of hyaluronan (HA) on the production
      of matrix metalloproteinase-1 (MMP-1) by rheumatoid synovial fibroblasts (RSF)
      stimulated by proinflammatory cytokines, tumor necrosis factor-a (TNF-a), and
      interleukin-1beta (IL-1beta). METHODS: HA of various sizes at various
      concentrations was added to monolayer cultures of RSF in the presence of TNF-a or
      IL-1beta, with or without pretreatment with a monoclonal antibody against CD44,
      OS/37. Concentrations of MMP-1 in cell lysates and conditioned media and of CD44
      on RSF were assayed by immunoblotting. MMP-1 expression was analyzed by reverse
      transcriptase-polymerase chain reaction. Binding of HA to RSF was evaluated by
      confocal microscopy using fluorescein-conjugated HA and OS/37. RESULTS: Treatment
      with HA (0.3 approximately 3.0 mg/ml) resulted in a significant decrease in the
      production of MMP-1 induced by TNF-a and IL-1beta, in a dose-dependent manner. HA
      of 250 approximately 2300 kDa at 3 mg/ml was found to suppress the induction of
      MMP-1 by TNF-a. HA decreased the cytokine-induced MMP-1 synthesis in RSF at mRNA
      and protein levels. The monoclonal antibody, which showed abundant expression of
      CD44 on RSF by immunofluorescein cytochemistry, partially blocked the binding of
      fluorescein-conjugated HA to RSF. Pretreatment with OS/37 reversed the inhibition
      of MMP-1 production in TNF-a or IL-1beta-stimulated RSF caused by HA. CONCLUSION:
      HA suppresses the production of MMP-1 by TNF-a or IL-1beta-stimulated RSF. Based
      on data from anti-CD44 treatment, HA binding to CD44 is directly involved in the
      suppression of MMP-1 production. Those results provide the rationale for a
      therapeutic role of HA in treatment of rheumatoid joints.

PMID- 12784386
TI  - Distribution of protein nitrotyrosine in synovial tissues of patients with
      rheumatoid arthritis and osteoarthritis.
AB  - OBJECTIVE: Because nitric oxide related species have been found in the inflamed
      joints of patients with arthritis, we investigated whether protein nitrotyrosine
      (a marker of tissue exposure to peroxynitrite) is present in their synovial
      tissues. METHODS: Protein nitrotyrosine was detected immunohistochemically and by
      Western blot analysis. Synovial tissues removed surgically from 12 patients with
      rheumatoid arthritis (RA) (mean age 63.7 yrs) and 20 with osteoarthritis (OA)
      (mean age 66.6 yrs) were studied. RESULTS: Nitrated proteins were detected
      immunohistochemically in all of 18 tissues examined. Diffuse staining of the
      stroma was seen in all patients, with more extensive staining in RA than OA (p =
      0.008). Intense staining was detected in some lymphocytes, but not in others,
      even within a single lymphoid aggregate. Neutrophils did not stain for
      nitrotyrosine. Vascular endothelial cells stained for nitrotyrosine but adjoining
      smooth muscle cells did not. Both cytoplasmic and nuclear staining was seen in
      macrophages, endothelial cells, and lymphocytes. Numerous bands of nitrated
      proteins were detected by Western blot analysis of 15 synovial tissue extracts.
      Inducible nitric oxide synthase (iNOS) was detected immunohistochemically in
      endothelial cells, macrophages, vascular smooth muscle cells, and synoviocytes.
      CONCLUSION: Nitrotyrosine-containing proteins were found in essentially all
      synovia from RA and OA patients. The most prominent site of nitration in all
      cases was the stroma. iNOS, the likely source of the nitrating species, was found
      in a variety of cell types.

PMID- 12784387
TI  - Leflunomide for the treatment of rheumatoid arthritis: a systematic review and
      metaanalysis.
AB  - OBJECTIVE: To systematically review the evidence from clinical trials on the
      efficacy and toxicity of leflunomide for the treatment of active rheumatoid
      arthritis (RA). METHODS: We searched Medline, Embase, Current Contents, and the
      Cochrane Controlled Trial Register for human randomized controlled trials (RCT)
      and controlled clinical trials up to December 2001. We also hand-searched
      reference lists and conference proceedings and consulted content experts.
      Relative benefit (RB), and weighted mean differences or standardized mean
      differences with their 95% confidence interval (95% CI) were calculated. RESULTS:
      Six RCT totaling 2044 patients with RA were included in this review. Using
      specific criteria, all trials were considered of high methodological quality.
      Leflunomide improved the ACR20 response rate roughly 2 times over placebo both at
      6 months (RB = 1.93, 95% CI 1.51, 2.47) and at 12 months (RB = 1.99, 95% CI 1.42,
      2.77). Other clinical outcomes of disease activity and function and radiological
      scores were also significantly better for leflunomide patients than those taking
      placebo. No significant differences for most of the outcomes were observed
      between leflunomide and sulfasalazine (SSZ) or methotrexate (MTX). Adverse events
      were more common in the leflunomide group, but withdrawal rates were fewer than
      for placebo. Overall, withdrawal rates and adverse events in the leflunomide
      group were not different from SSZ or MTX. CONCLUSION: Leflunomide improves all
      clinical outcomes and delays radiographic progression at 6 and 12 months of RA
      treatment compared to placebo. Its efficacy and adverse events at 2 years of
      treatment are comparable to SSZ and MTX. Longterm efficacy and toxicity remain to
      be established.

PMID- 12784388
TI  - Ultrasonography for assessment of subcutaneous nodules.
AB  - OBJECTIVE: To characterize a variety of subcutaneous lesions by their
      ultrasonographic (US) appearance, and establish these images as a starting point
      to measure changes with treatments. METHODS: Twenty-six patients with 48
      subcutaneous nodular swellings of various types were imaged using a portable US
      machine equipped with a 10 MHz linear transducer. All patients had a known
      diagnosis of a rheumatic disease. We used US to examine subcutaneous lesions and
      the underlying cortical surface of the bone or joint. Two measurements of some
      tophi and rheumatoid nodules were done on different dates to examine
      reproducibility of the measurements. RESULTS: Nodular lesions included 20 tophi
      and 20 rheumatoid nodules, 2 sarcoid nodules, 2 lipomas, and 4 synovial cysts.
      Tophi most often appeared as heterogeneous masses; hypoechoic areas in 2 tophi
      were decreased after aspiration of chalky liquid tophaceous material.
      Occasionally tophi had calcifications appearing hyperechoic with acoustic
      shadowing. Cortical bone erosions could be seen adjacent to some tophi. The
      nodules in patients with rheumatoid arthritis were often attached closely to the
      bone surface and less erosive to bone, allowing the cortical bone to be seen
      easily. The nodules were more homogeneous. Some showed a central sharply
      demarcated hypoechoic area, possibly corresponding to necrosis inside the
      rheumatoid nodules. Nodules were easily measured. The repeated measurements of
      both tophi and rheumatoid nodules showed excellent reproducibility. Lipomas had
      different echogenic patterns depending on composition of the associated
      connective tissue and position of the mass. They could be hypoechogenic,
      hyperechogenic, or mixed, but were easily distinguished by oval shapes with well
      demarcated capsules. Synovial cysts seen in this study had a characteristic
      hypoechoic pattern. CONCLUSION: Subcutaneous nodules examined by sonography show
      characteristics and patterns that, although not diagnostic, can be used to help
      distinguish their etiology. Tophi and rheumatoid nodules can be easily measured
      and these measurements used to help follow disease progression or response to
      therapy.

PMID- 12784389
TI  - All-cause mortality and vascular events among patients with rheumatoid arthritis,
      osteoarthritis, or no arthritis in the UK General Practice Research Database.
AB  - OBJECTIVE: To compare all-cause mortality rates and the incidence of major
      vascular events among patients with rheumatoid arthritis (RA), osteoarthritis
      (OA) without RA, or no arthritis using the UK General Practice Research Database
      (GPRD) while adjusting for age and sex. Clinic-based studies have found that
      patients with RA have higher all-cause and cardiovascular (CV) mortality than
      those without RA, after adjusting for age and sex. Much smaller elevations in
      risk have been found in the few community-based studies that have addressed this
      question. METHODS: After excluding patients with a history of myocardial
      infarction or cerebrovascular events, we followed a retrospective cohort of
      patients 40 years and older from GPRD practices until the earliest of death,
      disenrollment, or the occurrence of an incident vascular event. Using Poisson
      regression we compared age and gender adjusted incidence rates for RA, OA, or no
      arthritis. RESULTS: Five hundred and ninety-four practices contributed 2.37
      million patients (1.11 million men and 1.26 million women) to the analysis. Over
      a mean duration of followup of almost 5 years, age and gender adjusted all-cause
      mortality rates were 60 to 70% higher in patients with RA compared to patients
      with OA and those with no arthritis. For the various vascular endpoints, the age
      and gender adjusted incidence rates were 30 to 60% higher in patients with RA
      compared to both patients with OA and those with no arthritis during the study
      period. The rates in patients with OA and those with no arthritis were
      essentially the same. CONCLUSION: Compared to patients with OA and those with no
      arthritis, patients with RA had a higher age and gender adjusted incidence of all
      cause mortality and of major vascular events during almost 5 years of followup.

PMID- 12784390
TI  - Beneficial effects of rosmarinic acid on suppression of collagen induced
      arthritis.
AB  - OBJECTIVE: To assess the therapeutic potential of rosmarinic acid (RosA) in an
      inflammatory autoimmune arthritis model. METHODS: Collagen induced arthritis is
      established in male DBA/1 mice. Mice were administered daily with 50 mg/kg/day of
      RosA for 15 days from Day 21 post-immunization and inspected daily to determine
      the progression of arthritis. After termination of injection, affected hindpaws
      were subjected to histopathological analyses and immunohistochemical assays for
      cyclooxygenase-2 (COX-2) expression. RESULTS: Repeated administration of RosA
      dramatically reduced the arthritic index and number of affected paws.
      Histopathologic observations closely paralleled clinical data, showing that RosA
      treated mice retained nearly normal architecture of synovial tissues, whereas
      control mice exhibited severe synovitis. Synovial tissues from RosA treated mice
      exhibited remarkably reduced frequency of COX-2-expressing cells, compared to
      those from untreated mice. CONCLUSION: RosA suppressed synovitis in a murine
      collagen induced arthritis model; this effect may be beneficial for treatment of
      rheumatoid arthritis in clinical settings.

PMID- 12784391
TI  - Relationships between autoantibody responses to deletion mutants of Ki antigen
      and clinical manifestations of lupus.
AB  - OBJECTIVE: To determine the relationships between subtypes of anti-Ki antibodies
      and clinical manifestations of systemic lupus erythematosus. METHODS: The cDNA
      encoding full-length bovine Ki antigens or N- or C-terminal fragments were
      produced by polymerase chain reaction, and the fragments of Ki antigen were
      expressed as GST fusion proteins. Immunoreactivities of anti-Ki antibodies were
      tested by Western blotting. RESULTS: Of 60 sera reactive with full-length Ki
      antigen (KiF), 21 sera recognized only KiF. KiC5, a fragment containing the last
      69 C-terminal amino acids, was recognized by 23 sera. Since no significant
      difference was observed in prevalence of reactivities between fragments from KiC2
      to KiC5, a domain within the last 69 C-terminal amino acids was suggested to be
      the most common antigenic domain expressed among the GST fusion proteins. All 11
      sera reacting with a fragment containing the initial 81 N-terminal amino acids
      also recognized all other fragments. A domain homologous to SV40 nuclear
      localization signal was required for N-terminal recognition by 8 sera. Reactivity
      to the last 69 C-terminal amino acids and the initial 81 N-terminal amino acids
      showed specificities to systemic lupus erythematosus without and with Sjogren's
      syndrome, respectively. Sicca was significantly more prevalent in patients whose
      sera reacted with both N- and C-terminal fragments, while prevalence of anti
      SSA/Ro antibody was low. CONCLUSION: Ki antigen contains multiple epitopes
      recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune
      responses, associated with certain clinical subtypes.

PMID- 12784392
TI  - Cigarette smoking and disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the effect of cigarette smoking on disease activity and
      cumulative organ damage in systemic lupus erythematosus (SLE). Methods. Extensive
      clinical and demographic variables, including current and previous cigarette
      smoking, were collected from 111 SLE patients using a detailed interview
      administered questionnaire. Disease activity was estimated with the Systemic
      Lupus Erythematosus Disease Activity Index (SLEDAI). Cumulative organ damage was
      measured by the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index (SLICC/ACR). Smoking status was correlated
      with disease activity and cumulative organ damage, while statistically adjusting
      for the individual effects of potentially confounding demographic and clinical
      variables using analysis of variance followed by Fisher's least significant
      difference method. Results. Current smokers demonstrated significantly higher (p
      < 0.001) SLEDAI scores (15.6 +/- 7.8) than ex-smokers (9.63 +/- 6.00), and never
      smokers (9.03 +/- 5.75). This association remained significant (p = 0.001) after
      adjusting for all covariates, including ethnicity, education level, income level,
      alcohol use, age of onset of SLE, current age, mean duration of SLE, marital
      status, and hydroxychloroquine therapy. Current smokers also demonstrated
      significantly (p = 0.003) higher scores for both the neurological and non
      neurological components of SLEDAI. There was no significant difference in the
      SLICC/ACR scores across the various smoking groups, although there was a trend
      for more severe disease in current smokers. Conclusion. Cigarette smoking is
      associated with increased disease activity in SLE. These data further establish
      the association of SLE with cigarette smoking, and suggest that individuals with
      SLE should avoid all exposure to tobacco products.

PMID- 12784393
TI  - Smoking, alcohol consumption, and risk of systemic lupus erythematosus in the
      Black Women's Health Study.
AB  - OBJECTIVE: Several case-control studies, mostly of prevalent disease, have
      suggested that systemic lupus erythematosus (SLE) is positively associated with
      cigarette smoking and inversely associated with alcohol consumption. We
      prospectively investigated the associations of smoking and alcohol consumption
      with incident SLE in the Black Women's Health Study (BWHS). METHODS: In 1995,
      64,500 African-American women provided information on demographic
      characteristics, reproductive and medical histories, smoking, and alcohol
      consumption. Followup questionnaires in 1997 and 1999 ascertained incident cases
      of SLE. Cox proportional hazards regression was used to estimate incidence rate
      ratios (IRR) and 95% confidence intervals (CI). RESULTS: Sixty-seven women
      reported a new diagnosis of SLE and use of appropriate medication for that
      illness. In multivariate analyses, the IRR for current and past smoking were 1.6
      (both 95% CI 0.8-3.3). The risk was greater for women who began smoking before
      age 19 years (IRR 1.9, 95% CI 1.0-3.6). Neither current alcohol consumption (IRR
      1.0, 95% CI 0.4-2.4) nor past alcohol consumption (IRR 0.9, 95% CI 0.3-2.7) was
      associated with SLE. CONCLUSION: Our results suggest an increased risk of SLE
      among smokers, but no effect of alcohol consumption on risk. The inverse
      association of alcohol consumption with SLE found in studies of prevalent disease
      may have resulted from women with SLE giving up drinking.

PMID- 12784394
TI  - The frequency of thrombotic thrombocytopenic purpura in patients with systemic
      lupus erythematosus undergoing kidney biopsy.
AB  - OBJECTIVE: To characterize the frequency of thrombotic thrombocytopenic purpura
      (TTP) among patients with systemic lupus erythematosus (SLE) undergoing kidney
      biopsy. METHODS: A retrospective review of all renal biopsies of patients with
      SLE at Rush-Presbyterian-St. Luke's Medical Center was performed for the years
      1989 to 2001. RESULTS: Four cases of clinical and histopathological TTP were
      identified among the 257 patients with SLE who underwent renal biopsy during the
      12 year study period. CONCLUSION: TTP appears to occur at higher than expected
      frequency among SLE patients undergoing biopsy for unexplained renal failure.

PMID- 12784395
TI  - Pupillocynetic activity of substance P in systemic sclerosis.
AB  - OBJECTIVE: In systemic sclerosis (SSc), dysfunctions of peripheral nervous system
      (PNS) have been observed. Substance P (SP) instillation in human eye induces a
      cholinergic-independent pupil myosis. Pupil basal diameters (PBD) and pupil
      responsiveness to SP, expressed as area under the curve (AUC), were studied by
      pupillometry to assess SP-ergic fiber state and function in SSc. METHODS: Forty
      SSc patients [24 with limited (lSSc), 16 with diffuse (dSSc) disease] and 40
      controls underwent pupillometric evaluation. After evaluation of PBD, SP 10-3 M
      was instilled in one eye and placebo in the contralateral eye. Antinuclear (ANA),
      anticentromere (ACA), and anti-Scl-70 autoantibodies were correlated with PBD and
      AUC. RESULTS: PBD was significantly lower in SSc patients versus controls (p <
      0.001). PBD was minor in lSSc versus both dSSc and controls (p < 0.05), but no
      difference was found between dSSc and controls. In SSc, SP 10-3 M induced greater
      myosis compared to controls (p < 0.001). SP 10-3 M-induced myosis was higher in
      lSSc versus both dSSc and controls (p < 0.05). ACA significantly correlated with
      decreased values of PBD and AUC (p < 0.001). CONCLUSION: Our results show that
      PBD is reduced in patients with SSc and that SP induces a more intense myosis in
      SSc than controls. Moreover, in lSSc PBD is lower and SP increases the myosis in
      lSSc compared to dSSc and controls. This suggests a peculiar dysfunction of PNS
      in patients with the limited subset of SSc.

PMID- 12784396
TI  - Patterns of hospital admissions and emergency room visits among patients with
      scleroderma in South Carolina, USA.
AB  - OBJECTIVE: Little research has examined patterns of hospitalization and use of
      emergency rooms (ER) among patients with systemic sclerosis (SSc). We compared
      the incidence of hospitalizations and ER visits across 3 race groups (non
      Hispanic white, non-Hispanic black, other) and determined predictors of referral
      to the Medical University of South Carolina (MUSC), a major referral center for
      patients with SSc residing in the southeastern United States. METHODS: Data were
      obtained on all South Carolina hospitalizations (1996-2000) for patients who were
      ever hospitalized for a diagnosis of SSc during that time period. Hospitalization
      and ER incidence rates were determined in conjunction with corresponding
      population sizes obtained from the 2000 US Census, and rates were compared across
      race, sex, and age groups using Poisson regression models. Logistic regression
      was used to determine predictors of being treated at MUSC. RESULTS: The
      hospitalization incidence rate was significantly (p < 0.05) higher among blacks
      compared to whites (rate ratio 1.66; 95% confidence interval 1.41, 1.96), as was
      the ER incidence rate (rate ratio 1.78; 95% CI 1.50, 2.11). Even after adjusting
      for sex, age, median household income, primary insurance claim payor, county, and
      comorbidity, blacks were 60% less likely (p < 0.05) than whites to receive
      inpatient treatment at MUSC. Similar results were observed when comparing other
      non-whites to whites. CONCLUSION: The increased hospitalizations and ER visits
      among non-whites provide additional evidence of greater disease burden among
      these population groups. Despite this increased burden, non-whites are less
      likely to receive care at a major SSc referral center.

PMID- 12784397
TI  - Spontaneous chromosome damage (micronuclei) in systemic sclerosis and Raynaud's
      phenomenon.
AB  - OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in
      cultured peripheral lymphocytes of patients with systemic sclerosis (SSc),
      idiopathic Raynaud's phenomenon (RP), and suspected secondary RP, by means of
      molecular cytogenetic analysis. METHODS: We studied 43 patients with SSc, 13 with
      idiopathic RP, and 16 with suspected secondary RP and 25 healthy controls. As a
      marker of chromosome alteration we used the micronucleus (MN) assay. All subjects
      were also classified for antinuclear antibodies, anticentromere antibodies (ACA),
      or Scl70. To identify the mechanism of MN formation, we also performed MN
      fluorescence in situ hybridization (FISH) analysis using a pancentromeric DNA
      probe. RESULTS: Patients with SSc and subjects with RP showed significantly
      higher MN frequencies than controls (25.9 +/- 1.7 and 19.1 +/- 2.15,
      respectively, vs 9.4 +/- 2.2; p < 0.001). Subjects with suspected secondary RP
      displayed MN frequency (23.5 +/- 2.7) comparable to that of SSc patients, while
      spontaneous MN level in idiopathic RP subjects (13.6 +/- 3.0) did not differ
      significantly from controls (9.4 +/- 2.2). ACA positive subjects showed the
      highest MN frequencies (32.8 +/- 1.7) compared to subjects with a different
      antibody pattern (18.3 +/- 1.6). CONCLUSION: Our results show the presence of
      higher levels of micronuclei in circulating lymphocytes of patients with SSc and
      subjects with suspected secondary RP. They also suggest a possible role of ACA in
      determining cytogenetic anomalies. FISH analysis indicated that both
      aneuploidogenic and clastogenic events contributed to the formation of MN
      observed in SSc patients and subjects with suspected secondary RP.

PMID- 12784398
TI  - Bactericidal/permeability-increasing protein and cathepsin G are the major
      antigenic targets of antineutrophil cytoplasmic autoantibodies in systemic
      sclerosis.
AB  - OBJECTIVE: To study the prevalence and antigenic specificity of antineutrophil
      cytoplasmic autoantibodies (ANCA) in patients with systemic sclerosis (SSc).
      METHODS: Sera from 68 patients with SSc were screened for ANCA by indirect
      immunofluorescence (IIF) assay and for antibodies to myeloperoxidase (MPO) by
      ELISA. All sera positive for ANCA on IIF were analyzed for reactivity against
      antigenic targets other than MPO [bactericidal/permeability-increasing protein
      (BPI), cathepsin G, lysozyme, elastase, PR3, and lactoferrin]. Twenty-three sera
      negative for ANCA were also tested for antibodies to BPI and cathepsin G using
      ELISA. RESULTS: The study included 33 patients with diffuse and 35 with limited
      SSc. ANCA was detected in 24 of the 68 sera (35.3%). In these 24 sera the
      antigenic targets were BPI in 14, cathepsin G in 13, and MPO in 8. Sera of 11
      patients had reactivity against both BPI and cathepsin G. In sera, that were
      negative for ANCA, antibodies to BPI (4/23), cathepsin G (3/23), and MPO (1/44)
      were found in a small proportion of patients. Patients with antibodies to BPI had
      lower skin score, whereas no patient with antibodies to MPO had renal disease.
      CONCLUSION: BPI and cathepsin G are the major antigenic targets of ANCA seen in
      patients with SSc. Patients with antibodies to BPI had lower skin scores.

PMID- 12784399
TI  - Evaluation of functional disability using the health assessment questionnaire in
      Japanese patients with systemic sclerosis.
AB  - OBJECTIVE: To assess whether the functional disability in Japanese patients with
      systemic sclerosis (SSc) can be adequately evaluated by the Health Assessment
      Questionnaire (HAQ) developed in the United States. METHODS: The HAQ was
      completed by 121 Japanese patients with SSc, in whom SSc-specific physical
      examinations and laboratory tests were performed at the same time. Clinical
      findings associated with the disability index (DI) and individual components of
      the HAQ were examined using Student's t tests and Pearson's correlation tests.
      Logistic regression analysis was used to identify clinical findings that
      independently contributed to the increase in the HAQ-DI score. RESULTS: Japanese
      patients with SSc had significant functional disability, especially in the
      categories of eating and gripping, but the degree of disability was much less
      than was reported in previous studies carried out in the US. The increase in the
      HAQ-DI score was strongly correlated with increased total skin score, reduced
      oral aperture, reduced hand extension, increased finger flexion, subcutaneous
      calcinosis, flexion contractures, increased erythrocyte sedimentation rates,
      decreased percent vital capacity, and vascular involvement (p < 0.001 for all
      correlations). Multivariate logistic regression analysis showed that hand
      extension was the most important and an independent correlate of the HAQ-DI.
      CONCLUSION: Our multicenter, cross-sectional study has demonstrated that the self
      administered HAQ is a valuable assessment tool of functional disability in
      Japanese SSc patients, who have social customs different from Americans, but
      functional disability measured by the HAQ is potentially influenced by ethnic
      variability.

PMID- 12784400
TI  - Validation of the Sicca Symptoms Inventory for clinical studies of Sjogren's
      syndrome.
AB  - OBJECTIVE: Oral, ocular, and other dryness are the hallmark features of Sjogren's
      syndrome (SS). We constructed a new measure of sicca symptoms, the Sicca Symptoms
      Inventory, for the evaluation of patients with primary SS. METHODS: Female
      Caucasian groups of patients with primary SS, systemic lupus erythematosus, and
      rheumatoid arthritis and healthy controls were assessed for tear and saliva
      production and also completed a symptoms-profiling inventory construct-validated
      from primary SS patients' own vocabulary, augmented with sicca items from
      publications and participating clinicians. Multi-item facets of sicca and other
      discomfort were validated by factor analysis. RESULTS: Primary SS and other
      "sicca" conditions were highly discriminated from other rheumatic disorders and
      healthy controls on each dryness-related facet of oral and ocular discomfort.
      Selected symptom scores were as sensitive and specific to primary SS as the
      scores for saliva and tears, respectively, although the severity scores of
      symptoms and signs were only moderately correlated. CONCLUSION: These multiple
      question scales distinguish patients with primary SS from controls more precisely
      than previously used measures. Future studies will test if change in these
      symptom scores can serve as an outcome measure for clinical trials in SS.

PMID- 12784401
TI  - Sex steroid hormones in primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the relationships between concentrations of sex
      hormones and measures of disease activity in patients with primary Sjogren's
      Syndrome (pSS). METHODS: Fifty-four women were evaluated: 39 patients (age,
      Q1,Q3: 57.0 yrs; 46, 66) diagnosed with pSS and 15 patients (49.0 yrs; 45, 60)
      who did not meet diagnostic criteria for pSS. The following measures of disease
      activity were assessed: serological data [antinuclear antibody, rheumatoid
      factor, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum
      immunoglobulin levels (IgG, IgA, IgM), serum protein, anti-SSA, and anti-SSB],
      labial minor salivary gland focus score, salivary flow rates, and objective
      measures of eye dryness (fluorescein corneal staining and unstimulated Schirmer's
      I test). Spearman correlations were calculated between these indices of disease
      activity and serum levels of sex hormones: dehydroepiandrosterone (DHEA), DHEA
      sulfate, androstenedione, testosterone, dihydrotestosterone (DHT), estrone,
      estradiol, and sex hormone binding globulin (SHBG). RESULTS: Numerous differences
      were noted between cases and controls with disease activity measures. All median
      values of sex steroid hormones were within the range of normal for pSS cases.
      Positive correlations were noted between testosterone and ESR (r = 0.36, p =
      0.03), testosterone and serum protein (r = 0.37, p = 0.05), and testosterone and
      focus score (r = 0.44, p = 0.007). Negative correlations were present between
      SHBG and anti-SSA (r = -0.33, p = 0.05), SHBG and anti-SSB (r = -0.43, p =
      0.009), and DHT and CRP (r = -0.41, p = 0.05). No correlations were noted between
      estrogens and measures of pSS disease activity. CONCLUSION: Higher levels of
      disease activity (ESR, serum protein, and focus score) were associated with
      higher concentrations of testosterone. No correlation between disease activity
      and estrogens was found.

PMID- 12784402
TI  - Silent, or masked, giant cell arteritis is associated with a strong inflammatory
      response and a benign short term course.
AB  - OBJECTIVE: To determine the frequency, characteristics, and short term outcome of
      patients who have biopsy-proven giant cell arteritis (GCA) but no local symptoms
      that can be attributed to vasculitis inflammation [silent temporal arteritis
      (TA)] throughout the pretreatment course of the disease or an observational
      period lasting at least 2 months. METHODS: Of 175 consecutive patients with
      biopsy-proven GCA, 130 had typical cranial arteritis, 21 had silent vasculitis,
      and the remaining 24 had either discrete cranial symptoms (19 cases) or isolated
      extracranial vasculitis (5 cases). We sought to determine which of 15
      pretreatment characteristics were associated with silent TA, as compared with
      typical cranial arteritis, and assessed the short term outcome in these patients.
      RESULTS: Of 21 patients with silent GCA, 14 met criteria for fever of unknown
      origin. Aside from their different clinical presentation, this population was
      characterized by a longer delay in diagnosis (p = 0.003), a higher mean
      erythrocyte sedimentation rate (p = 0.002), higher C-reactive protein (p =
      0.002), and lower levels of albumin (p = 0.01) and hemoglobin (p < 0.0001).
      Permanent visual loss, which occurred in 24 patients (13.7%), exclusively
      involved those presenting with symptoms and/or signs suggesting cranial
      arteritis, especially those with frank cranial arteritis. This complication was
      associated negatively with the delay in diagnosis (p = 0.01), and marginally with
      the number of symptoms and/or signs suggesting cranial arteritis recorded in each
      patient (p = 0.07). Oral prednisone at a mean daily dose of 0.7 mg/kg resulted in
      satisfactory control of silent TA within 4 weeks in all patients but one, and
      could subsequently be safely tapered by half in a mean delay of 38 +/- 23 days.
      No differences were observed between patients with silent TA and other forms of
      the disease regarding the mean prednisone dose at 3 month followup (18.2 +/- 4.5
      vs 20.9 +/- 5.9 mg/day) and 6 month followup (14 +/- 4.4 vs 15.6 +/- 6 mg/day ).
      CONCLUSION: Silent TA may represent a distinct subset of giant cell arteritis,
      marked by a protracted inflammatory response and a relatively benign short term
      outcome, excellent response to corticosteroids, and no visual ischemic events,
      despite the long period of exposure to this complication before appropriate
      treatment.

PMID- 12784403
TI  - Sulfasalazine reduces the number of flares of acute anterior uveitis over a one
      year period.
AB  - OBJECTIVE: To evaluate the efficacy of sulfasalazine (SSZ) in the prevention of
      recurrent flares of acute anterior uveitis (AAU). METHODS: We included patients
      seen from June 1997 to October 2000 in this prospective, open, longitudinal study
      who fulfilled the following inclusion criteria: either (1) > or = 3 flares of AAU
      in the previous year or (2) > or = 2 recurrences of uveitis within 3 months
      before starting the trial. We excluded uveitis of infectious or malignant origin
      or patients with contraindications to the drug. The response criteria were
      defined as absence of symptoms and the presence of a normal ophthalmologic
      examination. The major outcome was the number of flares of uveitis over a one
      year period compared in the same group of patients with the flares along the
      previous year without SSZ. RESULTS: Three hundred ninety-four patients with
      uveitis were evaluated during the period of the study and 10 patients fulfilled
      the inclusion criteria. The mean number of flares in the pre-SSZ year was 3.4 (SD
      0.5), which was significantly reduced to 0.9 (SD 1.1) in the year of treatment (p
      = 0.007). CONCLUSION: SSZ treatment seems to reduce the number of flares over a
      one year period in patients with recurrent AAU.

PMID- 12784404
TI  - Antiinflammatory and chondroprotective effects of the aminobisphosphonate
      incadronate (YM175) in adjuvant induced arthritis.
AB  - OBJECTIVE: Incadronate is a third-generation bisphosphonate that suppresses bone
      resorption and is used to treat skeletal disorders and prevent bone loss in
      pathological conditions. We evaluated its therapeutic potential and
      antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat
      model of rheumatoid arthritis (RA). METHODS: Rats were administered incadronate
      subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0
      mg/kg/week, while a positive control group received phosphate buffered saline
      alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of
      bone and cartilage and the antiinflammatory effects of incadronate in rats with
      established AIA were assessed during treatment, with reference to the arthritis
      index, hind paw volume, and radiological and histological examinations. To
      establish whether incadronate affects the migration of inflammatory cells, a
      chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results.
      In vivo, incadronate suppressed the clinical manifestations of AIA in a dose
      dependent manner. In vitro, the various concentrations of incadronate suppressed
      the migration of macrophages, but the viability and adhesion of these cells were
      not suppressed. CONCLUSION: Incadronate not only inhibits bone destruction but
      also reduces cartilage degeneration and joint inflammation in rats with
      established AIA. The mechanism underlying these antiinflammatory actions of
      incadronate may be attributable to the inhibition of macrophage migration to the
      site of inflammation. Bisphosphonates might be effective in preventing the
      progressive joint destruction and inflammation seen in patients with RA.

PMID- 12784405
TI  - Determinants of synoviocyte clearance of arthritogenic bacteria.
AB  - OBJECTIVE: Persistence of intracellular organisms may play a critical role in the
      initiation and perpetuation of synovitis in reactive arthritis (ReA). We
      investigated factors that may influence local clearance of arthritogenic
      pathogens in ReA. METHODS: We studied 11 HLA-B27 positive patients with
      spondyloarthropathies and contrasted these patients with 6 HLA-B27 negative
      control patients with rheumatoid arthritis or osteoarthritis. We employed an ex
      vivo system in which human synoviocytes derived from patients with ReA are
      cocultured with arthritogenic pathogens, and intracellular clearance is measured
      by quantitating colony-forming units over time. RESULTS: The clearance kinetics
      of the organisms bore no relationship to the HLA-B27 status of the patient.
      Clearance of S. typhimurium over a 10 day period was accompanied by a progressive
      rise in nitric oxide (NO) production, but this appeared not to be rate-limiting,
      since (1) clearance kinetics were comparable between high versus low NO-producing
      synoviocytes; and (2) L-NMMA inhibition of NO production did not alter clearance
      kinetics of S. typhimurium. Interferon-g (IFN-g) was observed to have a small but
      measurable effect on bacterial clearance. In certain patients with ReA there was
      a paradoxical stimulatory response to IFN-g, in which the addition of IFN-g was
      accompanied by an increase in intracellular bacteria. This effect was found to be
      attributable to IFN-g mediated suppression of NO production in these cells. This
      pattern was not observed in B27 negative synoviocytes. CONCLUSION: Intracellular
      persistence of arthritogenic organisms may contribute to the cellular basis of
      ReA, but the molecular basis of the bacteriocidal pathways in synoviocytes has
      not been fully resolved. Our findings indicate that a direct effect of HLA-B27 on
      these events is unlikely, but that alterations in cytokine response profiles may
      play a contributory role. Characterizing these mechanisms holds the promise of
      more specific therapeutic interventions in this disease.

PMID- 12784406
TI  - HLA antigens and primary osteoarthritis of the hand.
AB  - OBJECTIVE: Many studies have examined genetic factors associated with either
      development or severity of primary osteoarthritis (OA). Analyses of the
      frequencies of HLA antigens in various OA populations have yielded conflicting
      results; an increased frequency of HLA-A1, B8, and DR4 alleles has been
      suggested. We investigated the interrelationship between HLA antigens and primary
      OA. METHODS: We analyzed the frequency of HLA-A, B, C, DR, and DQ antigens in 95
      patients (82 women, 13 men) with primary OA of the hands compared to 200 controls
      matched for age, sex, and ethnicity. Class I and Class II HLA antigens were
      evaluated using conventional serologic typing. RESULTS: No statistically
      significant difference in the distribution of HLA-A1 and B8 antigens was observed
      in patients with OA compared to controls. By contrast, HLA-B35, B40, DQ1, and CW4
      antigens were overrepresented in the OA patients. Haplotype analysis showed an
      association of B35-DQ1, B40-DQ1, and DR2-DQ1 with increased OA risk. CONCLUSION:
      Our results suggest a role of the HLA system in the etiopathogenesis of primary
      OA of the hand.

PMID- 12784407
TI  - Is there a difference in the perception of symptoms between african americans and
      whites with osteoarthritis?
AB  - OBJECTIVE: To determine if there is a difference in the perception of pain and
      functional disability between African Americans and Whites at any given
      radiographic severity of osteoarthritis (OA). Ethnic differences in utilization
      of joint replacement may reflect differences in the perception of symptoms of OA.
      METHODS: A cross-sectional survey included 596 male veterans (44% African
      Americans and 56% Whites) with chronic moderate to severe knee and/or hip pain at
      the General Medicine Clinics. The average age of the total cohort was 65.63 +/-
      9.5 years. The Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) for pain and function were the primary outcome measures of interest. All
      knee and or hip radiographs were graded using the Kellgren-Lawrence (K/L) grading
      system. RESULTS: African Americans and Whites were comparable with respect to age
      (65 +/- 9.5 vs 66 +/- 9, respectively); body mass index > or = 30 kg/m2 (53.9% vs
      58.8%); Lequesne severity score (11 +/- 4 vs 11 +/- 4); geriatric depression
      score (4.5 +/- 3.3 vs 5.0 +/- 3.8) and Charlson Comorbidity Index (2.3 +/- 2 vs
      2.5 +/- 2). African Americans had lower socioeconomic status with fewer high
      school graduates (57% vs 71%, p = 0.001), lower employment rate (8.4% vs 14.7%, p
      = 0.017), and lower total household incomes (41.4% vs 20.4% reported income <
      $10,000, p = 0.000). African Americans and Whites were not different in mean
      scores for WOMAC pain and WOMAC function when stratified by joint space
      narrowing, osteophyte and Kellgren Lawrence grades. After controlling for
      important covariates, ethnicity was not a significant predictor of WOMAC pain and
      function. CONCLUSION: In this sample of male veterans, African Americans and
      Whites perceived the same degree of pain and functional difficulties at any given
      radiographic severity of OA. Differences in the perception of symptoms cannot
      explain the observed ethnic disparity in utilization of joint replacement.

PMID- 12784408
TI  - Physiotherapy, including quadriceps exercises and patellar taping, for knee
      osteoarthritis with predominant patello-femoral joint involvement: randomized
      controlled trial.
AB  - OBJECTIVE: To design and carry out a randomized controlled trial of a complex,
      physical therapy based intervention for patello-femoral joint (PFJ)
      osteoarthritis (OA) of the knee, examining medium to longterm outcomes. METHODS:
      The participants, who had knee pain and predominant PFJ OA, were recruited from a
      large population based study. The study design was a controlled trial using
      prerandomization and a blind observer, comparing the intervention package with
      standard nonphysiotherapy treatment. The physiotherapy intervention was delivered
      in local community health centers and clinics and comprised education, quadriceps
      and functional exercises, and patellar taping delivered by a single
      physiotherapist in nine 30-minute sessions over 10 weeks, with advice to continue
      thereafter. The outcome measures were pain in the worse knee by 100 mm visual
      analog scale score, the disability domain of the Western Ontario and McMaster
      University OA index (WOMAC), and quadriceps muscle strength by maximum voluntary
      contraction. RESULTS: Eighty-seven patients were recruited to the study, 43 were
      randomized to the treatment arm. At 5 months post-baseline (10 weeks post
      treatment) the treatment group had a small decrease in pain and a significant
      increase in quadriceps strength of the index knee. After one year there were no
      significant differences in any outcome measure, most of which had returned
      towards pretreatment levels. CONCLUSION: The treatment package produced small
      improvements in knee pain scores and quadriceps muscle strength 10 weeks after
      the end of the treatment period. There was no difference between the 2 groups at
      12 months.

PMID- 12784409
TI  - Economic cost and epidemiological characteristics of patients with fibromyalgia
      claims.
AB  - OBJECTIVE: Fibromyalgia (FM) is characterized by widespread pain that can lead to
      significant patient disability, complex management decisions for physicians, and
      economic burden on society. We investigated the total costs of FM in an employer
      population. METHODS: Administrative claims data of a Fortune 100 manufacturer
      were used to quantify direct (i.e., medical and pharmaceutical claims) and
      indirect (i.e., disability claims and imputed absenteeism) costs associated with
      FM. A total of 4699 patients with at least one FM claim between 1996 and 1998
      were contrasted with a 10% random sample of the overall beneficiary population.
      Employee-only subsets of both samples also were drawn. RESULTS: Medical
      utilization, receipt of prescription drugs, and annual total costs were
      proportionately similar yet significantly greater among FM claimants than the
      overall sample (all p < 0.0001). Total annual costs for FM claimants were $5945
      versus $2486 for the typical beneficiary (p < 0.0001). Six percent of these costs
      were attributable to FM-specific claims. The prevalence of disability was twice
      as high among FM employees than overall employees (p < 0.0001). For every dollar
      spent on FM-specific claims, the employer spent another $57 to $143 on additional
      direct and indirect costs. CONCLUSION: Hidden costs of disability and
      comorbidities greatly increase the true burden of FM. Regardless of the clinical
      understanding of FM, when a claim for FM is present, considerable costs are
      involved. Findings suggest that within the management of FM there may be large
      cost-offset opportunities for reductions in patient, physician, and employer
      burdens.

PMID- 12784410
TI  - Patient-physician discordance in fibromyalgia.
AB  - OBJECTIVE: Discordance between patients' and physicians' health perceptions and
      satisfaction with the office visit in fibromyalgia (FM) has not been examined. We
      investigated this phenomenon to identify demographic, clinical, and psychosocial
      factors associated with patient-physician discordance on physical functioning,
      well being, and satisfaction with the office visit. METHODS: A sample of 182
      women were examined by a rheumatologist to confirm the FM diagnosis. Patients and
      physicians independently completed the Patient-Physician Discordance Scale to
      assess perceptions of health and satisfaction with the office visit. Patients
      also completed questionnaires pertaining to sociodemographics, social support,
      disability, perceived stress, and psychological distress following the office
      visit. Separate generalized estimating equations with forward selection,
      controlling for the possible dependence of outcomes among patients of same
      physician, were modeled for each measure of discordance. RESULTS: The highest
      discordance score was on satisfaction with the office visit; physicians
      systematically underestimated patients' level of satisfaction. Higher levels of
      satisfaction with social support (p < 0.02) and more psychological distress (p <
      0.03) were marginally associated with greater discordance on physical
      functioning. Higher levels of satisfaction with social support (p < 0.003),
      younger age (p < 0.02), and lower disability (p < 0.03) were associated with
      greater discordance on well being. More sexual abuse (p < 0.01) was significantly
      associated with more discordance on satisfaction with the office visit.
      CONCLUSION: There is a gap between what patients with FM and rheumatologists
      examining them experience during the office visit. Psychosocial factors
      contribute to our understanding of discordance on physical functioning, well
      being, and satisfaction.

PMID- 12784411
TI  - Enthesalgia in childhood: site-specific tenderness in healthy subjects and in
      patients with seronegative enthesopathic arthropathy.
AB  - OBJECTIVE: The presence of pain over an enthesis defines enthesitis and is a
      major (or sole) clinical feature of childhood spondyloarthropathies. However, the
      presence or degree of tenderness of the entheses in healthy children is unknown.
      We studied the prevalence of enthesalgia and pain thresholds over entheses in
      healthy children and whether these sites are different from those in patients
      diagnosed with seronegative enthesopathic arthropathy (SEA syndrome). METHODS: We
      examined 234 schoolchildren aged 8 to 16 years for enthesalgia; those reporting
      tenderness were compared to randomly selected patients with SEA syndrome
      previously diagnosed in a tertiary outpatient clinic. RESULTS: Enthesalgia in at
      least one site was found in 68 children (29%). Schoolchildren had fewer sites
      than patients (mean 1.2 +/- 2.8 sites vs 8.1 +/- 4.5 sites; p < 0.0001).
      Enthesalgia was not associated with age, sex, or self-reported activity level. In
      schoolchildren, pressure thresholds were higher with age (p < 0.0001), and in
      boys (p = 0.014), and were decreased in those with enthesalgia (p = 0.003). The
      metatarsal heads had the lowest pain thresholds. Significant sites specific for
      SEA patients were: plantar fascial insertion (p < 0.0001), Achilles tendon
      insertion (p = 0.001), sacroiliac joint (p = 0.002), and inferior pole of the
      patella (p = 0.003). Of these 8 sites, only 10% of schoolchildren reported
      tenderness in 3 sites compared to 56% of children with SEA syndrome. CONCLUSION:
      Enthesalgia is not rare in children; metatarsalgia or a limited number of tender
      entheses should not define enthesitis. Enthesalgia in 3 of the 8 specific tender
      entheses noted above may better define childhood enthesitis.

PMID- 12784412
TI  - Digital necrosis related to carboplatin and gemcitabine therapy in systemic
      sclerosis.
AB  - We present a woman with scleroderma who developed multiple ischemic digits after
      chemotherapy for lung cancer. The ischemia started during treatment with
      carboplatin and gemcitabine and required amputation of the affected digits. A
      review of the literature shows that thrombotic episodes coinciding with
      chemotherapy are not uncommon, though venous thrombosis occurs more frequently
      than arterial. Scleroderma patients are at particular risk for digital infarction
      because of their underlying vascular disease and associated Raynaud's phenomenon.
      This case illustrates the risk of severe digital ischemia and digital loss in
      patients with scleroderma during chemotherapy with carboplatin and gemcitabine.

PMID- 12784413
TI  - Polyarteritis nodosa presenting as acute leg ischemia.
AB  - We describe a 33-year-old hypertensive woman with otherwise apparently good
      health, in whom acute leg ischemia by acute occlusion of the 3 infrapopliteal
      arteries led to the diagnosis of polyarteritis nodosa (PAN). Angiography and
      ultrasound imaging showed multiple microaneurysmal and thrombotic lesions,
      notably in the kidneys and the 4 extremities. Cutaneous biopsy showed necrotizing
      angiitis. She was treated with corticosteroids. Ischemia improved progressively,
      with normal walking after several months. Three points were remarkable in this
      case of PAN: (1) its unusual presentation; (2) the absence of constitutional
      symptoms despite the diffuse distribution of vascular lesions; (3) the good
      visualization of peripheral microaneurysms by ultrasonography (US), suggesting a
      potential diagnostic interest for US examination of the limbs in PAN.

PMID- 12784414
TI  - Whipple's disease with destructive arthritis, abdominal lymphadenopathy, and
      central nervous system involvement.
AB  - We describe a patient with Whipple's disease who had an unusual erosive and
      destructive polyarthritis, massive abdominal lymphadenopathy, asymptomatic
      central nervous system involvement, and rare manifestations of orbital
      pseudotumor and orchitis with epididymitis. Taking oral therapy with trimethoprim
      sulfamethoxazole he had recurrent flares of orbital pseudotumor, an episode of
      orchitis with epididymitis, and persistent polymerase chain reaction T. whipplei
      positive cerebrospinal fluid. Resolution was achieved with a one month course of
      intravenous ceftriaxone and a 6 month course of azithromycin, and no relapse
      occurred during 24 months of followup.

PMID- 12784415
TI  - Subcutaneous, intramuscular, and intraosseous synovial cyst formation around the
      knee in rheumatoid arthritis/systemic lupus erythematosus overlap syndrome.

PMID- 12784416
TI  - Subacromial bursitis with rice bodies as the presenting manifestation of
      rheumatoid arthritis.

PMID- 12784417
TI  - Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis
      factor-alpha directed therapies in the treatment of spondyloarthritis.
AB  - Spondyloarthritis (SpA) represents a group of related arthritides characterized
      by their association with HLA-B27 and the development of sacroiliitis and
      enthesitis. Functional impairment, disability, and loss of quality of life may
      resemble that observed in rheumatoid arthritis. The SpA Research Consortium of
      Canada (SPARCC) is an informal association of rheumatologist members of the
      Canadian Rheumatology Association (CRA) with a special interest in therapeutics
      and outcomes research in SpA. Recent experience with anti-tumor necrosis factor-a
      (anti-TNF-a) directed therapies prompted a consensus-based evaluation of the
      evidence supporting their efficacy, safety, and appropriate use in SpA. We
      evaluated the clinical evidence in support of anti-TNF-a directed therapies in
      SpA. Medline was searched using appropriate keywords. Abstracts of the 1999-2002
      annual meetings of the American College of Rheumatology and the European Congress
      of Rheumatology were extracted and admitted if sufficient detail was available to
      determine the level of evidence. Recommendations were based on randomized placebo
      controlled trials (Level A evidence) and clinical studies without randomization
      (Level B evidence). Where the scientific literature was incomplete,
      recommendations reflected the consensus of SPARCC members (Level C evidence).
      Following development of an original draft document, consensus for revisions was
      achieved among members of SPARCC. The document was then posted on the CRA website
      prior to its final revision. The following recommendations have been endorsed by
      the Therapeutics Committee of the CRA: Infliximab and etanercept are indicated
      for reduction of signs and symptoms of moderate to severely active SpA in
      patients who have had an inadequate response to maximal doses of > or = 2
      nonsteroidal antiinflammatory drugs (NSAID) over a 3-month period of observation;
      and either sulfasalazine or methotrexate is indicated in those with predominantly
      active peripheral arthritis. Current evidence supports their use as monotherapy
      (level of evidence A) for at least one year. NSAID and/or second line therapy
      with either sulfasalazine or methotrexate can be continued concomitantly. There
      is no evidence addressing potential advantages or disadvantages of combining
      methotrexate with anti-TNF therapy for SpA. Recommended doses for adults are:
      infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter; etanercept
      25 mg subcutaneously twice weekly. No therapy has been shown to slow progression
      of axial disease in SpA, and prognostic factors for determining response to
      therapy remain to be determined. It is the position of the CRA that all
      therapeutic options should be equally available according to the best judgments
      of the treating physician and the informed decision of the patient.

PMID- 12784418
TI  - OMERACT Rheumatoid Arthritis MRI Studies Module.
AB  - The rationale for an OMERACT Module on the use of magnetic resonance imaging
      (MRI) in the assessment of rheumatoid arthritis (RA) is outlined. This article
      also details the way in which the RA MRI Working Group developed and undertook a
      series of structured exercises to evaluate the reliability and sensitivity to
      change of the RA-MRI score (RAMRIS).

PMID- 12784419
TI  - OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 3: an
      international multicenter reliability study using the RA-MRI Score.
AB  - We examined inter-reader agreement of the revised OMERACT 5 Rheumatoid Arthritis
      MRI Score (RAMRIS v3). Magnetic resonance (MR) images of 10 sets of
      metacarpophalangeal (MCP) joints 2-5 and 8 sets of rheumatoid arthritis (RA)
      wrists [1.5 T, coronal and axial T1 and T2 spin-echo, +/- fat saturation (FS), +/
      intravenous gadolinium (Gd)] were scored for (1) synovitis using a global score
      (0-3) and a direct measurement of synovial thickness (mm) and (2) three bone
      lesions: erosions, defects and edema, (score 0-10 by the volume of the lesion as
      a proportion of the "assessed bone volume" by 10% increments). Six readers from 5
      multinational centers performed all scoring. Three statistical methods were used
      to analyze the data: (1) single-measure fixed effects intraclass correlations
      (sICC) and average-measure fixed effects ICC (avICC), (2) percentage exact and
      close agreement, and (3) the smallest detectable difference (SDD). The sICC were
      moderate to good (between 0.60 and 0.91) for half of the joint sites for the 2
      synovitis scoring methods, and for bone erosions and bone edema. After adjusting
      for 6 readers, the avICC was very good to excellent (0.80-0.98) for two-thirds of
      the joint sites by lesion, excluding bone defects that performed relatively
      poorly, primarily because few readers scored these lesions. The aggregated scores
      with the best reliability were those with a wide range of scores, high ICC, low
      SDD, and low percentage SDD (< 33%). The metacarpophalangeal (MCP) bone erosion
      (sICC 0.58, avICC 0.89, %SDD +/- 27), wrist bone erosion scores (0.72, 0.94, +/-
      31%), the wrist synovitis global (0.74, 0.94, +/- 32%), and synovial maximal
      thickness (0.6, 0.94, +/- 32%) met these conditions. MCP joint synovitis global
      (0.76, 0.95, +/-35%), MCP joint bone edema (0.63, 0.91, +/- 34%), and wrist bone
      edema (0.78, 0.95, +/- 38%) performed marginally less well. Bone defects
      performed poorly (MCP joint 0.18, 0.46, +/- 56%; wrist 0.06, 0.24, +/- 55%). The
      revised OMERACT 5 RAMRIS has acceptable inter-reader reliability for measures of
      disease activity (synovitis global and bone edema scores) and damage (bone
      erosion score). Whether the score is sensitive to change will be determined by
      its performance in longitudinal and intervention studies.

PMID- 12784420
TI  - OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 4: an
      international multicenter longitudinal study using the RA-MRI Score.
AB  - The aim of this multireader, multicenter study was to assess the inter-reader
      reliability of the score in the assessment of disease status and progression. The
      exercise involved 10 sets of metacarpophalangeal (MCP, 2nd to 5th) joints and 10
      sets of wrist magnetic resonance images that were scored by experienced readers
      from 5 international centers. Synovitis was scored for each site using a global
      score (0-3). Bone abnormalities were assessed at 8 MCP joint sites and 15 wrist
      sites according to proportion of bone volume (0-10 for erosions and defects and 0
      3 for edema). Intraclass correlation coefficients (ICC) and smallest detectable
      differences for synovitis, erosions, and edema were acceptable, although better
      for status scores than progression scores. The agreement for MCP joints was
      better than wrists. Limited variation in the images for some findings resulted in
      low ICC. Bone defects had the poorest agreement and have been omitted from new
      scoring recommendations. Despite limited training, multicenter readers
      demonstrated acceptable levels of agreement.

PMID- 12784421
TI  - OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 5: an
      international multicenter reliability study using computerized MRI erosion volume
      measurements.
AB  - Scoring erosions on magnetic resonance imaging (MRI) is one method of estimating
      damage in patients with rheumatoid arthritis (RA), but it has limitations. The
      aim of this pilot study was to assess the feasibility and inter-reader
      reliability of computer assisted erosion volume estimation in patients with RA.
      Intra-reader and inter-occasion reliability was also assessed, and different
      slice thicknesses were compared in terms of erosion volume estimation. A 3 mm
      slice thickness 3D gradient-echo sequence followed by a 1 mm sequence was
      performed at baseline and repeated within 24 h with metacarpophalangeal (MCP)
      joints 2 to 5 of the dominant hand included in the field of view. Three readers
      were instructed to grade MCP 2 and 3 using the OMERACT grading system and then to
      measure the erosion volume of the same joints using OSIRIS software. The inter
      reader reliability of the grading method and the volume method was calculated, as
      well as the inter-occasion reliability, by comparing results from each reader
      from baseline to the followup scan. One reader performed repeat volume
      measurements on 5 patients to assess the intra-reader reliability. Five patients
      were included in the study. Expressed in terms of intraclass correlation
      coefficients (ICC), the inter-reader and inter-occasion reliability of the volume
      method were comparable to the existing OMERACT scoring system, but large
      systematic differences in volume estimations were found between readers. The
      intra-reader reliability was excellent. Good correlation was demonstrated between
      the total erosion scores and the total erosion volumes. For both erosion volumes
      and erosion scores, 1 mm and 3 mm acquisitions produced variable results between
      readers, with no clear pattern of underestimation or overestimation for either
      slice thickness. The volume estimation method was more time consuming, taking
      roughly 5 times as long as the scoring method. Computerized MRI erosion volume
      measurements are feasible, with high intra-observer and inter-occasion
      reliabilities. Despite high ICC, the inter-observer reliability is not sufficient
      for multicenter use without prior reader training and calibration. The optimal
      slice thickness was not determined.

PMID- 12784422
TI  - OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI
      acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system.
AB  - This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance
      image scoring system (RAMRIS) for evaluation of inflammatory and destructive
      changes in RA hands and wrists, which was developed by an international MRI
      OMERACT group. MRI definitions of important RA joint pathologies, and a "core
      set" of basic MRI sequences for use in RA are also suggested.

PMID- 12784423
TI  - OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Summary of
      OMERACT 6 MR Imaging Module.
AB  - Magnetic resonance image (MRI) scanning is a new method for imaging and
      quantifying joint inflammation and damage in rheumatoid arthritis (RA). Over the
      past 4 years, the OMERACT MR Imaging Group has been developing and testing the RA
      MRI scoring system (RAMRIS) for use in RA. The OMERACT filter demands that an
      ideal outcome measure satisfy the elements of truth, discrimination, and
      feasibility. The RAMRIS as it currently stands incorporates measures of joint
      inflammation and damage including bone erosion, edema, and synovitis. Tendonitis
      has not been scored because of feasibility issues; joint space narrowing,
      reflecting cartilage damage, has also been excluded as reliability was low at the
      small joints of the hands. Anatomical coverage of the score is currently
      restricted to the wrists and hands but can provide a basis for a more
      comprehensive score. The MR measurement of synovitis correlates closely with
      histological evidence and work continues on validating MR erosions with reference
      to radiographic techniques. The RAMRIS has demonstrated good reliability for bone
      erosion and synovitis at the wrists and metacarpophalangeal joints subject to
      reader training, with slightly lower levels of reader agreement for bone edema.
      Reliability was less satisfactory in discriminating between 2 time points, and
      further work is required if the score is to be used to monitor change.
      Feasibility also needs to be considered for the practical application of the
      score, including the time taken for scanning and scoring, as well as cost and
      safety issues. The OMERACT RAMRIS provides a framework for scoring inflammation
      and damage in RA upon which further modifications can be built. It has been
      endorsed by the MRI working group and OMERACT 6 participants as useful for
      inclusion as an outcome measure in clinical trials.

PMID- 12784424
TI  - Unclassified early arthritis is often spondyloarthritis.

PMID- 12784425
TI  - Effect of a diet program on lipid and lipoproteins, body weight, nutrient
      intakes, and quality of life in patients with systemic lupus erythematosus.

PMID- 12784426
TI  - Sustained response to infliximab in 2 patients with refractory relapsing
      polychondritis.

PMID- 12784427
TI  - [Performance of restoration surgeries in postburn stenosis of the esophagus and
      stomach].
AB  - The thirty-years experience of treatment of 987 patients with postburn stenosis
      of the gut upper parts was summarized. Of the total amount of restorational
      operations performed in 431 patients there were: esophagoplasty using colon--in
      313 (72.62%), small intestine--in 26 (6.04%), stomach--in 66 (15.32%), segment of
      colon and ileum on the vascular pedicle--in 10 (2.31%), autotransplantation of
      jejunal segment--in 2 (0.47%), esophagocardioplasty--in 5 (1.15%), plasty with
      application of local tissues--in 9 (2.09%). Total mortality had constituted
      6.96%, but during last 12 years it had subsided down to 1.91% due to perfection
      of the operations technique performed, new procedures introduction, the
      anesthesiological support improvement, wide usage of prophylactic measures for
      possibly occurring complications.

PMID- 12784428
TI  - [First experience of laparoscopic esophagocardiomyotomy for achalasia of the
      cardia].
AB  - The first experience of extramucosal laparoscopic esophagocardiomyotomy
      performance in 12 patients for achalasia of cardia was summarized. There were
      presented main technical stages of the operation, indications, early and
      immediate results of its application as well.

PMID- 12784429
TI  - [The need for liver transplantation in adult population of the Lviv region].
AB  - Hepatic transplantation constitutes a modern standard of a medical care giving to
      the patients with some diseases of this organ. According to the Lviv regional
      pathologomorphological bureau data there were choosed and analyzed in detail 144
      observations of the persons, died for the 6 years period due to hepatic pathology
      owing. The annual maximal quantity of retrospectively--possible recipients of
      liver constitutes 18.3 persons, minimal--14.8 persons. Maximal index of the Lviv
      region adult population necessity for hepatic transplantation constitutes 8.3
      interventions to 1 million of citizens, minimal one--6.7. Regional nosologic
      structure of the hepatic transplantation necessity corresponds with the world
      tendencies present.

PMID- 12784430
TI  - [The role of immune disorders in formation of local and systemic complications of
      severe acute pancreatitis].
AB  - There were studied the factors, which initiate the immune response in severe
      acute pancreatitis, in 57 patients of both gender ageing from 16 to 66 years, in
      whom the acute pancreatitis severity had constituted 3 marks and more (according
      to the Ranson criterions). In majority of the patients the combined type of the
      immune disorders had prevailed. The first stage of the disease was characteristic
      for metabolic hyperactivity occurrence with raising of HLA-DR+ level as well as
      of immunoregulating coefficient at the expense of the T-helpers quantity
      increase. In 47.1% of the patients with aseptic pancreonecrosis also the HLA-DR1
      leukocytic antigens were revealed in combination with normal phagocytic activity
      of neutrophils present in 85.3% of them. In these patients also most frequently
      were revealed such antigens as HLA-A1 (in 20.6% of observations), HLA-A9 (in
      29.4%), HLA-B13 (in 30.4%), HLA-B16 (in 20.6%). In 51.2% of patients, suffering
      infectionized pancreonecrosis, there was revealed HLA-DR2 lymphocytic phenotype.
      In them there were noted high suppressive activity of T-lymphocytes, lowering of
      phagocytic activity of neutrophils, activation of the aberrant adhesion molecules
      (ICAM-1, ICAM-3) on the background of higher concentration of interleukin-8
      present in the blood serum in comparison with such in patients, suffering aseptic
      pancreatic necrosis.

PMID- 12784431
TI  - [Prophylaxis and treatment of postoperative complications in patients with
      malignant hepatopancreatobiliary tumors complicated by jaundice].
AB  - Results of the patients treatment, in whom biliodigestive anastomosis was
      performed for hepatopancreatobiliary zone cancer, were adduced. Among early
      complications hepatorenal insufficiency, septic-purulent and thrombohemorrhagic
      complications, postoperative pancreatitis, an acute purulent cholangitis had
      prevailed. The late complications were mainly presented by the biliary ducts
      cicatricial stricture, the jaundice and cholangitis recurrency. To improve the
      results of treatment of early and late postoperative complications the complex of
      surgical and therapeutic prophylactic measures was proposed as well as the
      monitoring system, based on the active diagnostico-therapeutic tactics algorhythm
      elaborated, which was directed on revealing and removal of complications. The
      timely performance of relaparotomy and "second look" operation constitutes the
      principal surgical method used.

PMID- 12784432
TI  - [Surgical treatment of pancreatic fistula].
AB  - Results of treatment of 149 patients with external pancreatic fistula for 1990
      2000 yrs period were analyzed. Roentgencontrast fistulography, ultrasonic
      investigation, endoscopic retrograde pancreatography are the main diagnostic
      methods of the disease. Conservative therapy was conducted in 57 patients,
      sandostatin was administered in 0.1 ml dosage subcutaneously every 8 h during 5-8
      days. It turned to be effective in 42 (73.7%) of patients.
      Fistulopancreatojejunostomy, fistulojejunostomy, pancreatic resection of its
      part, carrying fistula, were the main methods of operative treatment.
      Postoperative complications occurred in 7 (7.6%) of patients. All the patients
      are alive.

PMID- 12784433
TI  - [Standardization of the report on clinical effects of surgical treatment of
      patients with obliterating atherosclerosis of the lower extremities].
AB  - To achieve the objectivization of the operation results performance, to compare
      them, to conduct a dynamic control of the reconstructed arterial segments
      passability and the course of the disease as well, the estimation of treatment
      efficacy in patients with obliterating atherosclerosis of the lower extremities
      arteries must be standardized for some factors, considering the change in the
      patient state and locus morbi. The authors had performed the analysis of
      approaches to solve this problem and proposed the criterions of the operative
      treatment efficacy estimation in patients with intermittent claudication and
      critical ischemia of lower extremities.

PMID- 12784435
TI  - [Organ preserving surgeries of the lungs].
AB  - Results of performance of a new organpreserving operation, the precise excision
      of pulmonary pathologic formation, were summarized in 172 patients, suffering
      hamartochondroma--in 120, fibroadenoma--in 7, solitary cyst--in 11, tuberculoma-
      in 32. The proposed operative method advantages in comparison with conventional
      procedures are: preservation of one or two unaffected pulmonary segments--in 115
      patients, the pulmonary lobe--in 38, the lung--in 19. The postoperative
      complications frequency is two times less. The ability to work was restored in 3
      5 mo after the operation. In the late follow-up period the complete clinical
      effect of treatment was observed.

PMID- 12784434
TI  - [Current possibilities of the diagnosis and surgical treatment of acute
      thrombophlebitis and severe forms of varicose disease].
AB  - The data on examination and surgical treatment of 35 patients, suffering severe
      forms of varicose disease in stage of trophic disorders occurrence and with an
      acute thrombophlebitis are adduced. The concept of an active surgical help,
      including thromboembolic complications prophylaxis, depending on thrombophlebitis
      localization, correction of the venous hemodynamics disorders and the staged
      closure of trophic ulcer is substantiated. Introduction of the proposed tactics
      had permitted to achieve satisfactory outcomes, including the trophic ulcer
      healing and the trophic disorders regression in all the patients operated on.

PMID- 12784436
TI  - [Mild and latent forms of coagulopathy and thrombocytopathy in surgical
      practice].
AB  - The most characteristic hemorrhagic signs and frequency of their occurrence in
      mild and latent forms of coagulopathy and thrombocytopathy were analyzed.
      Recommendations were formulated on the diagnosis, treatment and prophylaxis of
      hemorrhagic syndrome during and after operation conduction.

PMID- 12784437
TI  - [Preparation no-shpa forte for the treatment of renal colic].
AB  - In 24 patients there was studied up the preparation Nospa-forte efficacy in renal
      colic occurrence due to presence of calculus in ureter, basing on analysis of the
      pain syndrome dynamic, the heart rhythm changes, the central and systemic
      hemodynamics indexes, renal function and urinanalysis. There was established
      efficacy of the preparation in the pain syndrome removal, the blood circulation
      hyperdynamics reduction, the vegetative nervous system state optimization and the
      heart rhythm stabilization. It is expedient to use Nospa-forte in the treatment
      of various visceral pain.

PMID- 12784438
TI  - [Comparative evaluation of surgical approaches in operative treatment of patients
      with the fracture of proximal end of the femur].
AB  - Metalloosteosynthesis of neck and trochantarian region of the femur,
      endoprosthesis of the hip joint were performed in the treatment of the femur
      proximal end fractures. Significant frequency of early and late complications in
      patients, operated on using posterior approach, is caused by its traumaticity due
      to transsection of the muscles expanse, creation in them hematomas, significant
      quantity of the wound exudate. The perspectives of application of anterolateral
      approach in performing operations for fracture of the femur proximal end are
      proved.

PMID- 12784439
TI  - [Transcutaneous intrahepatic portosystemic shunting as a method of treatment of
      decompensated portal hypertension].

PMID- 12784440
TI  - [Surgical treatment of bacterial endocarditis of mitral and tricuspid valves in
      combination with splenic abscess and aneurysm of the iliaca communis artery].

PMID- 12784441
TI  - [Endoprosthesis of the coronary arteries using transradial approach].

PMID- 12784442
TI  - [Videothoracoscopic removal of the foreign body from the left pleural cavity].

PMID- 12784443
TI  - [What surplus value achieves].

PMID- 12784444
TI  - [E-learning in general practice: a never ending story?].

PMID- 12784445
TI  - [Anna Haag House in Stuttgart: lively home of 3 generations under one roof].

PMID- 12784446
TI  - [Total intravenous anesthesia (TIVA): brief and painless?].

PMID- 12784447
TI  - [Postoperative nursing in the recovery room: security about the critical hours].

PMID- 12784448
TI  - [Prevention and therapy of perioperative hypothermia: warming system].

PMID- 12784449
TI  - [Nursing patients with sepsis--1: Seconds are decisive].

PMID- 12784450
TI  - [Coping with stress on the intensive care unit: because the human is human].

PMID- 12784451
TI  - [Perioperative fasting in childhood: hunger and thirst are not necessary].

PMID- 12784452
TI  - [Risk of accidental falls--3: Immediate help is vital].

PMID- 12784453
TI  - [Humanitarian aid in Iraq: in the name of hope (interview by Katrin Balzer)].

PMID- 12784454
TI  - [Acute postoperative confusion: a common phenomenon with largely unknown
      etiology].

PMID- 12784455
TI  - [Results of the "DAK-BGW Health Report": nurses wish for more time].

PMID- 12784456
TI  - [Working in other parts of the world: dream goals America, Australia, New Zealand
      -is the venture worthwhile?].

PMID- 12784457
TI  - [From case to case: confusion and mistakes].

PMID- 12784458
TI  - [Academic aspects of nursing: time for changes].

PMID- 12784459
TI  - [Wound management 5--Unconventional methods: more questions than answers].

PMID- 12784461
TI  - [Transition nursing--a model?].

PMID- 12784460
TI  - [Nursing between claims and reality: workload tolerance as professional secret].

PMID- 12784462
TI  - [Post-coital contraceptive--a solution?].

PMID- 12784463
TI  - [Nursing phenomena-based typology for electronic data processing-assisted
      collection and documentation of nursing processes--development, evaluation,
      results].

PMID- 12784465
TI  - [Palliative care, new guidelines from the National Accreditation and Health Care
      Evaluation Agency].

PMID- 12784466
TI  - [Patient education in the program at the congress of the Nursing Research
      Association].

PMID- 12784467
TI  - [Handling of cytotoxic drugs, be careful of risks].

PMID- 12784468
TI  - [Suicide prevention and the creation of national violence database is the order
      of the day].

PMID- 12784469
TI  - [Epilepsy comes out of the shadows].

PMID- 12784470
TI  - [Physiopathology of scarring. I--scarring factors: 2/2 extracellular matrix and
      growth factors].

PMID- 12784471
TI  - [Wounds and dressings note. 2--hydrocolloids].

PMID- 12784472
TI  - [Conflicting views on pain and palliative care].

PMID- 12784473
TI  - [Quality of life and patient satisfaction in palliative care centers].

PMID- 12784474
TI  - [Towards a new approach to care].

PMID- 12784475
TI  - [The power of words].

PMID- 12784476
TI  - [Education as apprenticeship for autonomy].

PMID- 12784477
TI  - [Auto-dialysis, a transfer of competence].

PMID- 12784478
TI  - [Enterostomy nurses, pioneers in education].

PMID- 12784479
TI  - [Education of children and adolescents with bladder disorders].

PMID- 12784480
TI  - [Patient education in cardiovascular diseases].

PMID- 12784481
TI  - [B. Use of antibiotics. 9/ Bacterial meningitis].

PMID- 12784482
TI  - [Chronic intestinal diseases in the dog: a review].
AB  - The most commonly encountered chronic enteropathies in dogs are inflammatory
      bowel disease (IBD), food allergies, and small intestinal bacterial overgrowth.
      Recent research in the field of immunopathogenesis of IBD and food allergy in
      human beings have made available new therapeutic options with immunomodulatory
      drugs. However, the mechanisms involved in the pathogenesis of canine IBD and
      food allergy have not been elucidated so far. Further studies focusing on the
      immunological dysregulation in the mucosa as well as clinical trials with new
      therapeutic modalities are needed to improve our knowledge and approach to these
      chronic diseases in dogs.

PMID- 12784483
TI  - Echinacea powder: treatment for canine chronic and seasonal upper respiratory
      tract infections.
AB  - An open multi-centered veterinary clinical trial, comparing conditions before and
      after treatment with a herbal preparation, containing the powdered root of
      Echinacea purpurea, was conducted by 6 practicing veterinarians in Switzerland.
      The plant-based immune stimulant was administered to 41 dogs with manifestations
      of chronic and seasonal upper respiratory tract infections, including
      pharyngitis/tonsillitis, bronchitis and kennel cough. Each animal was at an
      individual stage of the disease, with various symptoms and different severity
      scores, at start of treatment. There was no control group. Echinacea powder (1:3)
      was administered with the food at a dose of 1.0 g/10 kg body weight once daily
      for 8 weeks. Overall efficacy showed significant improvement for 92% of 39 dogs
      after 4 weeks of treatment and this was confirmed after 8 weeks. Significant
      reductions of severity and resolution of typical clinical symptoms, of clear
      nasal secretions, enlargement of lymph nodes, dry cough, dyspnea and dry lung
      sounds, were evident after 4 weeks. Only two adverse effects, not suspected to be
      attributable to the study drug, were recorded. Because quality and stability of
      the Echinacea powder were defined, using an analytical standard and purity tests,
      these data suggest, that the Echinacea preparation can be recommended as a well
      tolerated alternative treatment of canine upper respiratory tract infections.

PMID- 12784485
TI  - [What is the social responsibility for French medical schools at the beginning of
      the 21st century?].

PMID- 12784484
TI  - [A specific staining for the middle piece of sperm and its possible application].
AB  - A special staining technique for the middle piece of sperms is described in
      different species (cow, horse, sheep, goat, pig). Staining was performed with
      frozen or fresh semen. The mitochondria in the middle piece could not always be
      stained with the same intensity. Using 600-fold magnification, subunits of the
      middle-piece could be observed, but only on fresh collected and immediately
      stained sperms. When kept in the refrigerator for more than 3 days, the observed
      subunits disappeared. A positive correlation between staining intensity and
      enzyme activity could be indicative for sperm motility and also fertilizing
      capacity.

PMID- 12784486
TI  - [The social responsibility of medical schools: questions and stakes].

PMID- 12784487
TI  - [World Health Organization strategies "Towards Unity for Health" and the social
      responsibility of medical schools].
AB  - One may wonder why multiple endeavours conducted worldwide over the last five
      decades to reform health systems have not achieved their expected outcomes. In
      light of increasing fragmentation, the current health system must be substituted
      by a true systems vision along with political will to create a unity of action
      between the five main stakeholders, namely: policy-makers, health care service
      managers, professionals and professional associations, academic institutions
      including medical schools, and civil society. Such synergy can only be
      established if the partners share the same commitment to core values such as
      quality, equity, relevance and cost-effectiveness in the health care field.
      Through its functions of providing education, training, research, and services,
      the medical school has the potential to induce reflection and stimulate action
      leading to a more coherent, effective, and equitable health system and policies.

PMID- 12784488
TI  - [The Geneva experience: the Department of Community Medicine].
AB  - The mission of the Department of Community Medicine at the Geneva University
      Hospitals is to offer the underserved and marginalised populations guaranteed
      access to the health system and to promote education and research in general and
      internal medicine (primary care). The activity with a two-fold focus--medical
      social and academic--demonstrated by the type of care offered to homeless people
      and other clandestine groups allows for the achievement of a number of objectives
      of the Towards Unity for Health programme. However, evidence to date emphasises
      that such a structure remains fragile.

PMID- 12784489
TI  - Changing world, changing doctors, changing education!
AB  - Future developments in the community will underline the need to provide a
      community-oriented health care system in which public health doctors collaborate
      with general practitioners, as the hospital-based health care system that
      currently exists in many countries will not be able to solve the problems of
      health care in the future. Increasing populations, increasing mobility all over
      the world, spread of new diseases (aids/hiv and ebola virus for example) will
      have great impact on our societies and the expectations of the societies and
      patients of their doctors. Most societies in which our young doctors will serve,
      expect their adults to live on healthily into their 80th. That means that the
      society of the future will be a double aging society (more older people who are
      older than before) with all concomitant burdens of degenerative chronic diseases.
      How should we handle the problems in 2025 when our capacities stay restricted to
      what we once learned in 2002? For this purpose the medical faculties have to
      change their curricula. The medical faculties will have to educate different kind
      of doctors, different from the doctors they have educated for many decades. These
      doctors must collaborate with other health care workers in primary health care
      teams. Collaboration in these teams requires mutual trust, win-win situations and
      agreement on the principles of health promotion programs. Only by collaboration
      between public health care and individual, personal health care it will be
      possible to achieve unity for health for all people. In the future both public
      health doctors and general practitioners need each other's complementary support
      and since they share the same area of interest, they need to work together.

PMID- 12784490
TI  - [The experience of the Faculty of Medicine at Sherbrooke University].
AB  - There is no Faculty of Medicine in the New Brunswick province of Canada. Thirty
      three percent of its population is francophone. In an effort to improve the
      health status of this population, which is known to be inferior to that of its
      anglophone counterpart, and to fill the gap in terms of the lack of francophone
      physicians, a partnership was developed with the University of Sherbrooke's
      medical school. Therefore, a francophone medical training programme was
      established in New Brunswick, and as a community-based programme, it is oriented
      to serve the specific needs of this target group. This integrated and
      collaborative approach between the principal health partners has had a positive
      impact on improving the health status of the francophone population and on the
      francophone medical resources. It is a solid demonstration of the Towards Unity
      for Health approach and of the social responsibility of a medical school.

PMID- 12784491
TI  - [Management of diabetic children at the University Hospital Center of Rabat: an
      example of partnership or personal initiative on the periphery of the school of
      medicine?].
AB  - In Morocco there are at least 10,000 children under the age of 15 who suffer from
      type 1 diabetes who, due to the lack of appropriate management and care, are
      extremely susceptible to repeated hospital re-admission and long-term disabling
      degenerative complications. With the aim to reduce the frequency of
      complications, a specialised outpatient clinic was created at the children's
      hospital in Rabat in 1986. A multi-disciplinary team provides medical care as
      well as initial training and continuing education to the patients and their
      families according to a standardised protocol. The 700 young diabetics who are
      monitored in the clinic are at present autonomous in the delivery of their own
      daily treatment and continue to increasingly improve. After 10 years, this group
      of patients has experienced a diabetic retinopathy rate which is six times lower
      than since the onset of their illness. The programme is administered in
      partnership and with the financial support of a private sponsor and assistance of
      a parents' association. The programme is designed in compliance with the WHO
      Towards Unity for Health strategy and its core principles, namely: relevance,
      equity, quality, and effectiveness. In order to achieve sustainability, the
      programme needs an adopted geographic management structure and more formalised
      relationships linking the partners. Nevertheless, the programme could be
      considered as a laboratory experiment for the School of Medicine, in its search
      to create a wider social movement. This level of commitment implies recasting the
      foci of the medical training curriculum, promoting therapeutic patient education,
      giving more attention to the hospital's operations and building sustainable
      partnerships.

PMID- 12784492
TI  - [A regional public health research network INSERM "PRISMAL" (perception,
      representation and risk management in rural health settings)].
AB  - The PRISMAL (Perception, representation and health risk management in rural
      settings) network comprises three academic research teams, two health insurance
      agencies, and two health care networks in the Franche-Comte region that share
      their expertise to study the relationship between health and the rural
      environment. Three main objectives guide the network's activities and are linked
      to the following questions: 1) What are the epidemiological changes linked to the
      rural setting; what are their causes and effects? 2) What are the relationships
      between the rural environment, health risks, behaviours in seeking health care,
      access to health care services and quality of life? 3) What are the perceptions
      and representations of the affected populations on health risks specific to the
      rural setting? Research activities utilise specific diseases as examples of the
      result from interaction with the rural environment, such as "farmer's lung",
      alveolar echinococcosis, occupational risks for farmers, lung cancer, suicide
      attempts, premature birth, and vascular stroke. The partnership's framework
      extends well beyond the medical world and includes ecologists, geographers,
      sociologists, administrators and environmental technicians.

PMID- 12784493
TI  - [Improving the medical treatment of minors who are victims of sexual assault or
      physical abuse: a receiving center and partnership between a psychiatric hospital
      and university hospital].
AB  - The aim of the partnership is the establishment and operation of a centre open 24
      hours a day which receives and treats adults and underage victims of sexual
      assault and physical abuse coming from the greater metropolitan area of Besancon.
      The centre also provides the victims and their families with adapted forensic and
      psychotherapeutic assistance. The mechanisms to carry out the project will be set
      out in a contract between the two hospitals, including the resources of the two
      institutions. The centre will fit into the existing network of partners which is
      already operational in Besancon. The role of the University of Besancon and the
      Faculty of Medicine will be to promote research in the field of physical abuse,
      its causes and effects, and to train future physicians who will later be in
      charge of handling these types of cases in their careers.

PMID- 12784494
TI  - ["Research, medicine and tomorrow"].
AB  - In recent years health networks have developed as an essential new element in the
      organisation of the French health system. Under the auspices of the Regional
      Agency for Hospitalisation, the Franche-Comte was established in 1996 as per the
      Agency's order to implement a policy which facilitated the development and
      expansion of such networks. A Regional Federation of Health Networks was recently
      created in order to accompany the implementation of this policy so as to ensure
      coherence and efficiency. This article briefly presents one such health network
      in order to provide an example of the operational axis common to all networks.
      Furthermore, it presents the Regional Federation of Health Networks from Franche
      Comte in order to highlight the necessity for research on the coordination and
      collaboration between the different health networks. Finally, the reader is
      invited to question the potential role of the Faculty of Medicine in this schema
      for the future expansion of the health system to one which focuses on health
      rather than medicine, taking into account the new professional practices and the
      new occupational fields which have arisen as a result of the development of
      health networks.

PMID- 12784495
TI  - [Impact of new information and communication technologies (NTIC) on hospital
      administration and patient management. Care Network for Diagnosing and Treating
      Neurologic Emergencies].
AB  - The combination of specialised in-patient management, the development of
      diagnostic and therapeutic tools, the standardisation of procedures and
      organisation of the dies will allow for improving the prognosis of neurological
      patients seen in emergency situations. In order to achieve this objective, the
      Networks for Diagnosing and Treating Neurological Emergencies (RAIDS-UN) in
      Franche-Comte (FC) aim to better the quality of in-patient management for
      emergency on-set neurological pathologies such as traumatic brain injuries and
      strokes, the preparation and structuring of the dies for diagnosis and treatment,
      and assistance in neurology decision making. Based upon the needs of networks
      which approach the problem from two different directions--the RAIDS-UN/FC network
      (for neurological emergencies) and the RAIDS-UN/AVC network (for prevention and
      treatment of strokes)--they should both be able to benefit from new information
      and communication technologies (ICTs) in order to promote and support innovations
      in practice and contribute to the improvement in quality and health promotion
      effectiveness. In light of these developments, one may better understand the
      significance of the School of Medicine's role in training experts, advisors and
      supervisors as well as in providing a high level of quality and effective
      continuing education. Since 2001, the expansion of the RAIDS-UN networks has
      emphasised the need for the development of new professional specialties arising
      on the border between technology and medicine. The operation of these networks
      requires a strong partnership with health professionals and strategically relies
      upon a regional dynamic interaction which includes the hospitals, the city, the
      institutions and the university. It is in this manner that the RAIDS-UN networks
      will support other initiatives such as the Towards Unity for Health project.

PMID- 12784496
TI  - [Comment on revised guidelines in treatment of idiopathic Parkinson syndrome].
AB  - Treatment of idiopathic Parkinson's has become increasingly complex during the
      past years. A revision of the guidelines for treatment which had been published
      in 1998 by a study group of the Swiss Neurological Society became necessary.
      Emphasis is again put on the correct choice of medication for the start of
      treatment. The new guidelines also contain hints to the management of the
      problems of long term treatment.

PMID- 12784497
TI  - [Why do Parkinson patients fall? How can falls be prevented? Etiologic,
      therpeutic and preventive aspects].
AB  - Parkinsonian patients suffer often from falls. There are a lot of causes.
      Postural instability is an important risk factor for falls in Parkinson's
      disease. Referring to postural instability and falls the outcome of therapeutic
      measures using drugs is poor. An interdisciplinary therapeutic approach and
      general measures can help preventing falls in patients with Parkinson's syndrome.

PMID- 12784498
TI  - [Pitfalls in diagnosis of idiopathic Parkinson syndrome].
AB  - In general the diagnosis of idiopathic Parkinson's disease is considered to be
      easy and safe. In the last few years several studies have demonstrated that this
      in reality is not the case. A number of other syndromes have to be differentiated
      from idiopathic Parkinson's disease. One must be aware that in substantial number
      of cases the natural history has to be observed before a safe diagnosis can be
      made.

PMID- 12784499
TI  - [A deal with the Devil and Beelzebub].

PMID- 12784500
TI  - [Selective adhesion molecule inhibitors. Natalizumab in multiple sclerosis and
      Crohn's disease].

PMID- 12784501
TI  - [Individualized therapy: drug monitoring with the Genchip. Symposium of the Study
      Group in Clinical Pharmacy of the Germany Pharmaceutical Society, Berlin.
      October, 9-10, 2002].

PMID- 12784502
TI  - Individualization of drug dosage--past, present and future.
AB  - The development of drug immunoassays led to the introduction of therapeutic drug
      monitoring and the use of population pharmacokinetic (PK) methodology to develop
      guidelines for individualizing drug dosage. Recognition of pharmacodynamic (PD)
      variability and identification of PK parameters that best correlate with clinical
      response has occurred in several areas including oncology, infection and
      immunosuppression. In the future, drugs will be selected to suit the genetic
      characteristics that determine the likelihood of a response, while
      individualization of dosage will consider genetic information on drug metabolism.

PMID- 12784503
TI  - [Therapeutic drug monitoring of aminoglycosides as an additional pharmacy
      service].

PMID- 12784504
TI  - [Individual therapy in oncology].

PMID- 12784505
TI  - [Individualized therapy through monitoring of drug concentration in the
      biophase].

PMID- 12784506
TI  - [Therapeutic drug monitoring of new antidepressives and antipsychotics].

PMID- 12784507
TI  - [Therapeutic drug monitoring of antidepressives--therapeutic and health economics
      advantages].

PMID- 12784508
TI  - [Pharmacogenomics and gene expression analysis. Functional genome research for
      individual application to patients].

PMID- 12784509
TI  - [Sore muscles].

PMID- 12784510
TI  - [Antibiotic-associated diarrhea and pseudomembranous colitis. Treatment and
      prevention of recurrence].

PMID- 12784511
TI  - [110th year Nederlands Tijdschrift voor Tandheelkunde. 2. Root canal treatment,
      intra-canal disinfectants and bacterial culture: past and present].
AB  - Fifty years ago the Dutch Journal of Dentistry published methods and opinions
      concerning root canal treatment. Qualitative bacterial culture, inclusion of
      aggressive disinfectants, as well as antibiotics and widening of the apical
      constriction were carried out. Nowadays, because of several reasons, these are
      not clinical practice anymore. Controversy over the clinical consequences of
      bacterial presence in tubules and in the peri-apical area prevailed in the past
      and seem to be prevalent once again.

PMID- 12784512
TI  - [Availability and services of dentists under pressure?].
AB  - Signals in society point to a shortage of dentists in the Netherlands. Aim of
      this study is to explore how patients, against the background of supposed
      shortage, judge the availability and services of dentists. For this research the
      'Consumerspanel Health Care', in which 1.395 persons participate, was asked to
      complete a postal questionnaire. Response rate was 73.8%. Results show that there
      are presently no serious problems for patients with the services of dentist due
      to the presumed lack of dentists. The patients were very satisfied with the
      accessibility and the services delivered by the dentists in the Netherlands. With
      the availability there seem to be some possible problems.

PMID- 12784513
TI  - [Prediction of dental behavior problems in preschool children].
AB  - Aim of this study was to investigate behavioural and emotional problems in
      preschool children in relation with behaviour problems during a highly stress
      provoking dental treatment. Eighty one healthy children between 2 and 4 years
      referred to the clinic of Special Dental Care (SBT) in Amsterdam were selected,
      based on dental need (extraction of one or more primary incisors). Each child was
      sedated with oral midazolam. Their behaviour was rated by registering the degree
      of acceptance during four consecutive time periods of the dental treatment. Prior
      to the treatment parents were asked to fill in a questionnaire. No significant
      correlations between temperament and behaviour were found with the total CBCL
      profile or its subscales. This confirms the results of earlier studies that the
      relationship of temperament, dental anxiety and behaviour problems is a complex
      matter and not yet fully understood. It is also indicated that within the entire
      treatment a child's behaviour is closely related to its behaviour in the preceded
      treatment step.

PMID- 12784514
TI  - [Ectodermal dysplasia syndrome].
AB  - Ectodermal dysplasias (ED) are a heterogeneous group of disorders characterized
      by developmental dystrophies of ectodermal structures, such as hypohidrosis,
      hypotrichosis, onychodysplasia and hypodontia or anodontia. All forms of this
      heterogeneous group are genetically transmitted. Two genes are localized and
      identified, namely ectodermal dysplasia anhidrotic (EDA) and downless (DL).
      Currently the genes and gene products are defined, but the function of the
      proteins is not fully known. The location of the genes has enabled prenatal
      diagnosis and a more accurate identification of possible carriers. Medical
      counseling provides genetic information concerning the specific diagnosis,
      recurring risks, prenatal approach, identification of risk carrying relatives,
      and social, economic and psychological problems. Evaluation and diagnosis are
      essential immediately after birth.

PMID- 12784515
TI  - [A radiolucency in the articular eminence of the temporal bone: an air bubble?].
AB  - A case is described in which the orthopantomogram by coincidence showed an
      anomaly of the left articular eminence of the temporal bone, which is based on an
      extremely pneumatised mastoid bone. Because of the medical history a CT-scan was
      made of both temporomandibular joints. The CT-scan showed an extremely
      pneumatized articular eminence at the left side. The orthopantomogram might show
      a radiolucency in the articular eminence of the temporal bone as a coincidental
      appearance. In cases with a positive medical history for pathological deformaties
      or in cases where surgery has to be performed on the articular eminence of the
      temporal bone further radiodiagnostic examination is indicated.

PMID- 12784516
TI  - [Behcet's syndrome].
AB  - A dentist referred a 35-year-old woman to the department of oral and
      maxillofacial surgery because of recurrent aphtous-like changes of the oral
      mucosa and persisting pain. She also experienced similar complaints about her
      eyes and genitals. This combination of symptoms was suspect for Behcet's disease.

PMID- 12784517
TI  - [Anthrax].
AB  - Anthrax is a severe infectious disease by Bacillus anthracis. It can cause
      massacres among large herbivores, but means also a threat to humans. The latter
      develop mainly cutaneous anthrax, which they mostly survive. Inhalation can lead
      to more severe infections which, without medical intervention, are virtually
      always lethal. At the moment the disease draws much attention since it is thought
      to be a potential weapon in the hands of bioterrorists.

PMID- 12784518
TI  - [Sequelae of divorce].

PMID- 12784519
TI  - [Practice in spelling in remedial groups--results of an evaluation study in
      secondary education].
AB  - OBJECTIVE: This study aims to evaluate in a school-based tutoring setting a
      training program for spelling (Marburger Rechtschreibtraining) that has proven
      effective in non-school settings. A spelling training program already in use at
      the school serves as the control condition. METHODS: A total of 37 second- and
      third-graders rated by their teachers as spelling disabled participated in the
      study. In addition to their regular lessons, the children received two added
      lessons in small tutoring groups each week. RESULTS: The skills of the children
      in the tutoring program had increased significantly two years later regardless of
      the method used. This effect was confirmed both by tests as well as by teachers'
      and parental reports. However, the children's emotional attitudes towards school
      failed to change significantly. The control group that had received no tutoring
      improved as well. CONCLUSIONS: Tutoring spelling disabled children in small
      groups is an effective method for improving their reading and spelling abilities.
      Nevertheless, the fact that the skills of children in the control group without
      any tutoring also improved raises a number of questions. The choice of method in
      our study had no effect on the outcome. Our study was unable to systematically
      evaluate a number of potential influences (such as sample selection); these
      should be investigated further.

PMID- 12784520
TI  - [A questionnaire for assessment of "temprament in early childhood" as judged by
      parents].
AB  - OBJECTIVES: This study assesses a German version of Rothbart's Infant Behavior
      Questionnaire for the internal consistency, inter-correlations and stability of
      the scales. Associations between the scales with maternal depression and anxiety
      are analyzed. METHODS: Independent samples of infants aged 6 to 8 months and 10
      to 12 months (n = 149, respectively n = 109) and their mothers were studied. A
      longitudinal study of a sample of 101 mother-infant pairs was carried out at the
      infant's age of 4, 8 and 12 months. RESULTS: The internal consistency and
      independence of the five scales on the questionnaire are satisfactory. The
      stability coefficients correspond to a good degree to those of the American
      version of the IBQ scales. CONCLUSIONS: Thus a German version is now available
      that can be used in research and practice to measure the features of early
      childhood temperament by parental report.

PMID- 12784521
TI  - [Disorder attribution in psychiatric problems of adolescents. A pilot study of
      inventory validation of disorder attribution of psychiatric problems in
      adolescents].
AB  - OBJECTIVES: The first Questionnaire on Disorder Concepts for Mental Problems in
      Adolescents (SPPJ) was developed on the basis of the attributional theory (health
      locus of control) and validated in a population of 54 adolescents with mental
      disorder hospitalized primarily as in-patients. METHODS: Analysis of consistency,
      correlation with the test for locus of control in health and illness (KKG-Test),
      scale intercorrelation, correlation with the Frankfurt Self-Concept Scales,
      therapy cooperation and prognosis. RESULTS: The SPPJ distinguishes between causal
      attributions and locus of control and proves to be a reliable measuring
      instrument that delivers satisfactory correlations to the statement of general
      measuring instruments (KKG-Test). Contrary to our expectations there is no
      significant positive correlation between internal locus of control and
      cooperation and prognosis. An external, powerful-others causal attribution has a
      negative effect upon cooperation, while an external powerful-others locus of
      control has a positive effect upon it. CONCLUSIONS: Adolescent self-assessment of
      mental problems is a defined research subject different from illness or health
      concept variables in adults or concerning bodily illness. Adolescents who are
      less inclined to blame others for their problem and who value professional
      competence are probably more accepting of interventions and more compliant.
      Further research in this area is necessary. On the basis of the attributional
      theory more attention must be paid to the substantial difference between locus of
      (treatment) control and causal attributions.

PMID- 12784522
TI  - [Rett syndrome: individual differences in developmental and behavioral markers
      and psychosocial stress].
AB  - OBJECTIVES: Rett Syndrome is a severe neurological developmental disorder caused
      by a genetic mutation on the long arm of the X chromosome (Xq28). This disorder
      is characterized by a loss of purposeful hand use, verbal language, and specific
      behaviors. METHODS: Data were obtained from a survey of the parents of 83 girls
      on pre-verbal skills (Pre-verbal Communication Schedule), behavioral
      characteristics and emotional expression (Rett Syndrome Behaviour Questionnaire)
      and on maternal psychosocial stress (Handicap-related Problems for Parents
      Inventory). RESULTS: There is considerable individual variability in the
      developmental and behavioral characteristics which is not explained as a function
      of age. Maternal stress correlates with the daughters' mood, anxious reactions
      and night-time behaviors. CONCLUSIONS: Some implications for diagnosis and family
      counseling are discussed.

PMID- 12784523
TI  - [Sleep disorders in hyperkinetic children--correlation with arousal disorders,
      differential diagnosis and comorbidity].
AB  - OBJECTIVES: Sleep disorders are frequently observed in Attention Deficit
      Hyperactivity Disorder (ADHD). At the same time, however, there is little
      evidence of their prevalence and their specific characteristics. Also unclear is
      a possible pathogenetic relationship between disturbed sleep and the core
      symptoms of ADHD. There are still very few findings on the role of comorbid
      internal and neurological disorders like sleep apnea and restless legs syndrome
      in the differential diagnosis of ADHD. METHODS: We present an overview of the
      current literature, describing the most important results concerning sleep
      disorders in ADHD. RESULTS: A principal goal of future assessments is to
      ascertain whether sleep problems in children with ADHD represent unspecific
      concurrent symptoms or whether they play a substantial role in the pathogenesis
      of ADHD. CONCLUSIONS: Moreover a possibly increased risk of comorbid sleep
      disordered breathing disorder might be an important issue in the differential
      diagnostic considerations with regard to ADHD.

PMID- 12784524
TI  - ["Body and soul and friendships destroyed". Behavior therapy of a 14-year-old
      adolescent with alcohol dependence syndrome].
AB  - OBJECTIVES: About 250,000 children and adolescents in Germany are dependent upon
      alcohol or at severe risk of developing an alcohol disorder. Whereas adults who
      abuse alcohol benefit from a variety of therapy manuals and numerous institutions
      offering long-term disorder-specific care, the situation with regard to
      adolescent patients needs to be upgraded. METHODS: We present the behavioral
      therapy of an alcohol-dependent 14-year-old boy, focusing on a version of Petry's
      therapy manual for alcoholism (1996) that has been adapted for the treatment of
      adolescents. The efficacy of worksheets as a supplement to the usual behavior
      therapy, or social or family interventions in the treatment of alcohol-dependent
      adolescents is discussed.

PMID- 12784525
TI  - [Causes of otalgia from outside the ear].
AB  - Two patients, a man aged 50 and a woman aged 61 years, complained about otalgia
      without a hearing disorder. Both patients exhibited slight mucosal redness of the
      upper airway at examination of the ear, nose, and throat, but no other
      abnormalities. Subsequent CT investigations of the ear and paranasal sinuses
      revealed no pathology in either patient. The first patient's condition
      deteriorated; he was eventually found to have a bronchial carcinoma that might
      have involved the vagal nerve. The second patient, who had a diaphragmatic
      hernia, improved dramatically once her daily dose of omeprazole had been
      augmented. It seems that both patients suffered from otalgia referred by the
      vagal and/or glossopharyngeal nerve.

PMID- 12784526
TI  - [The Dutch College of General Practitioners' practice guideline 'Delirium in
      elderly people'; response from clinical geriatrics].
AB  - Delirium in elderly people is a severe condition that requires vigorous medical
      attention. Therefore, the Dutch College of General Practitioners has duly chosen
      to develop a practice guideline 'Delirium in elderly people'. It is likely that
      many general practitioners are only partly familiar with delirium in elderly
      people because the prevalence of delirium in general practice is low. Therefore,
      one of the objectives of the practice guideline should be to improve the
      diagnostic process. However, several diagnostic issues merit further attention.
      For example, the guideline does not contain a diagnostic algorithm and the
      description of the clinical presentation of a delirium is brief. In addition, the
      guideline lacks a clear overview of the most important risk factors for a
      delirium as well as a careful description of the difference between delirium and
      dementia.

PMID- 12784527
TI  - [The Dutch College of General Practitioners' practice guideline 'Delirium in
      elderly people'; response from psychiatry].
AB  - Delirium is a common psychiatric illness among the medically ill and is
      associated with significant morbidity and mortality. Although delirium may
      develop at any age, the elderly are particularly vulnerable. Since the number of
      elderly with chronic diseases, dementia, sensory handicaps and the use of several
      (anticholinergic) medications--all predisposing factors for delirium--is rising,
      it is essential that general practitioners can recognise, adequately diagnose and
      treat delirium. This guideline may aid the general practitioner in diagnosing and
      treating this generally underestimated psychiatric disturbance in somatically ill
      elderly patients. Evidence on clinical features, differential diagnosis,
      prevalence, course, aetiology, and risk factors for delirium in primary care is
      lacking. In general hospitals, the prevalence of delirium in the elderly is about
      10-40%; it is probably much less in primary care. This guideline does not provide
      an adequate description of the clinical presentations of delirium, and does not
      sufficiently stress the importance of recognising any new behavioural problem in
      an elderly patient as an indication of possible delirium.

PMID- 12784528
TI  - [Kidney transplantation: more kidneys from living donors, individualised
      immunosuppression and better results].
AB  - In the period 1996-2001, the number of transplanted postmortal kidneys decreased
      from 425 to 380, while at the same time the number of kidneys transplanted from
      living donors increased from 81 in 1996 to 155 per year in 2001. There was a
      striking increase in the proportion of living non-related donors (59/155).
      Although the short-term results of kidney transplantation have improved, and
      kidneys are very rarely lost as a consequence of acute rejection, the average
      life of a transplanted kidney has scarcely improved. Chronic allograft
      dysfunction is now the major cause of transplant loss. This process is hardly
      influenced by the immunosuppressive drugs currently used. To improve the
      cardiovascular risk profile, several centres discontinue the use of cyclosporin,
      tacrolimus or prednisone at 6 or 12 months after transplantation or substitute
      these with other drugs. This is complicated by acute rejection episodes in 10-20%
      of patients. With the arrival of a number of new immunosuppressive drugs the risk
      of rejection might be reduced.

PMID- 12784529
TI  - [Twenty-five years of cyclosporin use in transplantation medicine].
AB  - Cyclosporin has greatly improved the short and medium-term outcomes for solid
      organ transplantation. However, the effect on the long-term outcome has been less
      impressive. This can partly be attributed to the side effects of cyclosporin, and
      partly to the fact that the use of cyclosporin has not led to a reduced incidence
      of chronic allograft nephropathy. Efforts to minimise these side effects have led
      to the development of the microemulsion form of cyclosporin and improved methods
      for therapeutic drug monitoring (dosage based on blood levels instead of body
      weight). Finally, the introduction of new immunosuppressive drugs has made it
      possible to further reduce the dose of cyclosporin; this might eventually lead to
      cyclosporin-free immunosuppressive regimens.

PMID- 12784530
TI  - [Summary of the Dutch College of General Practitioners' practice guideline
      'Delirium in elderly people'].
AB  - The Dutch College of General Practitioners' practice guideline 'Delirium in
      elderly people' contains a number of key messages. These are: Consider the
      diagnosis of delirium in the case of changes in consciousness and attention,
      incoherent thinking or disorientation, if this picture developed over a short
      period of time (hours to days) and if the symptoms vary over the 24-hour period.
      Delirium is provoked by one or more somatic disorders; investigation and
      treatment of these disorders is an essential part of managing delirium. It is
      often difficult to distinguish delirium from dementia and depression. Although
      delirium is generally reversible, the prognosis in the elderly is relatively
      poor. If delirium is accompanied by fear or agitation, haloperidol is the drug of
      first choice, but in delirium induced by alcohol withdrawal or benzodiazepine
      withdrawal, a short-acting benzodiazepine such as lorazepam or oxazepam is
      indicated. Part of the treatment, but also prevention of delirium is focused on
      inducing factors that can provoke a delirium, such as medication with an
      anticholinergic effect, polypharmacy, inadequate nutrition, dehydration, sleep
      deprivation, immobility and sensory handicaps.

PMID- 12784531
TI  - [Diagnostic image (139). An intellectually disabled man with a distended abdomen.
      Coprostasis in a mentally disabled patient].
AB  - A 41-year-old intellectually disabled man was admitted because of a distended
      abdomen and diminished defecation frequency. Abdominal radiography indicated free
      intraperitoneal gas but CT showed coprostasis.

PMID- 12784532
TI  - [Favorable results of conservative treatment with isosorbide dinitrate in 25
      patients with fourth-degree hemorrhoids: a pilot study].
AB  - OBJECTIVE: To evaluate application of isosorbide dinitrate 1% ointment in the
      treatment of fourth-degree haemorrhoids. DESIGN: Prospective pilot study. METHOD:
      Twenty-five consecutive patients, 12 men and 13 women, with a median age of 48
      years (range: 30-78), presenting in the period October 1999-December 2001 with
      fourth-degree haemorrhoids, were treated with isosorbide dinitrate 1% ointment.
      RESULTS: In 24 out of 25 patients (96%) the objective, reduction of the
      stangulated haemorrhoids and relief of pain, was achieved. In one patient the
      haemorrhoids were not reduced. This patient was cured after classic
      haemorrhoidectomy. Two patients interrupted the treatment because of severe
      headache, but after renewed instructions they continued the therapy and were
      cured. CONCLUSION: Isosorbide dinitrate 1% ointment gave good results in the
      treatment of fourth-degree haemorrhoids, with only few side effects.

PMID- 12784533
TI  - [Another case of West Nile fever in the Netherlands: a man with encephalitis
      following a trip to Canada].
AB  - Shortly after his return to the Netherlands from a trip to Ontario, a part of
      Canada where infection with West-Nile virus has been reported, a 69-year-old man
      became increasingly confused and generally unwell, accompanied by fever. The
      clinical picture was compatible with viral encephalitis and this was supported by
      EEG findings and the results of the cerebrospinal-fluid examination. MRI of the
      brain did not contribute to the diagnosis. The patient was treated with aciclovir
      because herpes simplex encephalitis was suspected, and he recovered from his
      illness within a few days. The EEG normalised as well. The most important
      remaining symptom was diminished short-term memory function. After the patient
      was discharged, rising antibody titres against West-Nile virus were found in two
      consecutive sera; there were no antibodies to other encephalitis-causing viruses
      (such as Q fever virus and St. Louis encephalitis virus). This case report
      concerns the second imported case of West-Nile fever in the Netherlands and the
      first one with encephalitis.

PMID- 12784534
TI  - [A gastric signet ring cell carcinoma as the first expression of a breast
      carcinoma].
AB  - A 73-year-old woman presented with dull pain in the epigastric region, a rapid
      feeling of fullness upon eating and a weight loss of 10 kg in 6 months. Further
      examination showed linitis plastica due to a signet ring cell carcinoma in the
      stomach, multiple bone metastases, and an occult, small breast tumour.
      Immunohistochemical comparison of the tumours strongly suggested that all cases
      involved a metastasised breast carcinoma. At check-up after one year of tamoxifen
      treatment, the complaints had disappeared and the activity of the tumour marker
      had dropped. Gastric metastases from breast carcinoma are rare. Nevertheless,
      this possibility should be kept in mind in women presenting with malignancies of
      the stomach and mastopathy. Hormonal treatment and chemotherapy may result in
      reasonable palliation.

PMID- 12784535
TI  - [Hypersexuality during use of levodopa].

PMID- 12784536
TI  - [St. John's wort flowers and basis for use...].

PMID- 12784537
TI  - [Nicastrin--a protein with a hinge function].

PMID- 12784538
TI  - [From a 2500 year old apotropic comes a current antidepressive. The cultural
      history and mistique of St. John's wort].

PMID- 12784539
TI  - [The example: St. John's wort. Manufacturing and quality aspects of plant
      extracts].

PMID- 12784540
TI  - [Formulation of St. John's wort extract. A medicinal obstacle course].

PMID- 12784541
TI  - [What is known about St. John's wort? Phytochemistry and pharmacology].

PMID- 12784542
TI  - [The pharmacology of St. John's wort extract. Plausibility for therapeutic
      application as an antidepressive?].

PMID- 12784543
TI  - [New therapeutic studies and meta-analysis. St. John's wort extract vs.
      synthetics].

PMID- 12784544
TI  - [Charge conformity and biopharmaceutic characterization. St. John's Wort extract
      preparations in comparison].

PMID- 12784545
TI  - [Adverse drug effects and interactions. What is the current thinking about the
      use of St. John's wort?].

PMID- 12784546
TI  - [Do phytogenic drugs offer a savings potential? Pharmacoeconomics of plant
      antidepressives].

PMID- 12784547
TI  - [Position paper of the Working Group on Drug Control-Pharmaceutical Analysis of
      the German Pharmaceutical Society to establish principles for criteria of
      acceptance].

PMID- 12784548
TI  - [Biology of bovine herpesviruses].
AB  - Cattle are the natural host of herpesviruses. Since now four different bovine
      viruses have been described as members of the family Herpesviridae. The prototype
      of the bovine herpesviruses, Bovine Herpesvirus type 1 (BHV-1), is the causative
      agent of infectious bovine rhinotracheitis (IBR), infectious pustular
      vulvovaginitis (IPV) and infectious balanoposthitis (IBP). The related BHV-5 is
      an exotic neurovirulent agent and like BHV-1 a member of the genus
      Varicellovirus, within the subfamily Alphaherpesvirinae. BHV-2, also an
      alphaherpesvirus but grouped into the genus Simplexvirus is the causative agent
      of bovine herpes mammilitis and pseudolumpy skin disease. In contrast, BHV-4, a
      member of the subfamily Gammaherpesvirinae, is not known to cause any disease.
      Beside bovine herpesviruses there are few other herpesviruses which can infect
      cattle. Infections of cattle with these herpesviruses have either clinical or
      diagnostic importance, based on a close antigenic relationship to BHV-1 of some
      ruminant herpesviruses. This article deals with the molecular virology of bovine
      herpesviruses and the pathogenesis of bovine herpesvirus infections and provides
      an overview over herpesviruses that can infect cattle.

PMID- 12784549
TI  - [The new BHV-1 regulation].
AB  - The first amendment to the BHV-1 Regulation in late 2001 marked the first step
      towards sanitation. This also proved necessary in view of the environment in the
      European Community because the amending regulation will, in conjunction with the
      compulsory notification of BHV-1, allow operators to achieve medium-term trade
      advantages via the so-called Article 9 status laid down in Directive 64/432/EEC.
      Yet, some of the provisions of the BHV-1 Regulation are still questionable under
      animal disease legislation so that this first step must surely be followed up by
      a second step. Article 2 of the Regulation dated 12 December 2002 merely amended
      the vaccination intervals, the number of vaccinations required for basic
      immunization as well as the facts constituting an administrative offense.

PMID- 12784550
TI  - [Diagnostic markers in the prevention of bovine herpesvirus type 1: possibilities
      and limitations].
AB  - The usage of glycoprotein E (gE)-deleted BHV-1 marker or DIVA (differentiating
      infected from vaccinated animals) vaccines in combination with the accompanying
      determination of gE-specific antibodies is one of the basic parts of BHV-1
      eradication programs in Germany. Following the adoption of the "Legislation for
      the protection of cattle holdings from an infection with Bovine Herpesvirus Type
      1" in 1997, several million gE-antibody assays were conducted. Up to now,
      commercially available gE-blocking enzyme linked immunosorbent assays (ELISAs)
      are the only test systems available for the detection of gE-specific antibodies.
      However, there are some difficulties to meet the high requirements on their
      performance. Therefore, role and function of gE in the virus and the host as well
      as the principle of gE marker assays, the test design and the capability of the
      mainly used ELISAs are illuminated in this paper. Additionally, suggestions
      concerning the optimal usage and the correct application of gE-blocking-ELISAs
      are discussed.

PMID- 12784551
TI  - [Comparative studies with three different bovine blood sample BHV-1 ELISA tests:
      indirect ELISA and bG-blocking-ELISA].
AB  - A total of 2754 bovine blood samples were examined for BHV1 antibodies in three
      different BHV-1 ELISA tests. The tests used were the CHEKIT Trachitest 2nd. Gen.
      "Bestatigungstest" Serum, the CHEKIT-BHV-1-gB-ELISA (Bommeli
      Diagnostics/Intervet), and the BHV-1-gB Antibody Test Kit (IDEXX). A first
      testing identified 111 (4.0%) of the samples as positive and 2501 (90.8%) samples
      negative in all three tests. Onehundredand-fortytwo (5.2%) of the samples showed
      a not negative result in at least one of the two gB-ELISAs. The testing was
      repeated for 139 of the 142 samples and still 89 (3.2%) samples were found with
      discrepant results. The remaining 50 samples showed a negative reaction in the
      three ELISA tests. After Western blot analysis antibodies against glycoprotein B
      (gB) of BHV-1 were only detected in 11 of the 89 samples with a not negative
      reaction in at least one of the gB-ELISAs. Three of the 50 ELISA-negative samples
      showed a positive reaction in the Western blot. The high number of positive
      results in the gB-ELISAs which were negative in the Western blot assay leads to
      the conclusion that gB-ELISAs may have a lower specificity as the indirect ELISA.
      Introducing the gB-ELISA as the standard test for BHV1 serology in Bavaria would
      result to an increase of the number of BHV-1 positive farms by 8% (gB IDEXX) or
      20% (gB Bommeli) 20%.

PMID- 12784553
TI  - [Eradication of BHV-1 in cattle herds in Saxony-Anhalts using a vaccine lacking a
      marker--report of an experience].
AB  - The present article reports about the experiences during the current BHV-1
      eradication programme in Saxony-Anhalt started in 1996. An overview about the
      reasons, the basic situation, the issue and the present state of the eradication
      is given. Furthermore were shown, that an eradication of Bovine Herpes Virus type
      1 by using gE-deleted vaccines is possible.

PMID- 12784552
TI  - [BHV-1 eradication program in Bavaria: a marker-independent strategy].
AB  - In Bavaria a BHV-1 eradication program was initiated in 1986 and was changed to a
      compulsory program in 1998. The eradication success increased progressively from
      < 50% in 1986 to 87% of the farms in 2002. BHV 1-free farms are controlled by
      bulk milk serology twice a year along with blood serology in animals that are
      negative but from herds where positive field virus infected animals are present.
      All serological tests are performed with an indirect ELISA test, all positive
      results are confirmed by a gB ELISA. Currently about 100.000 virus infected
      cattle are in Bavarian herds, approximately 80% of these animals are in heavily
      infected herds (> 10 infected animals). These herds comprise about 5% of all
      Bavarian herds. The eradication of the virus in these heavily infected herds is
      the most diifficult, whereas the prevention of new infections appears
      controllable. In this review current problems in BHV1 eradication are named and
      possible improvements are discussed.

PMID- 12784555
TI  - [Heterogeneity of ruminant pestiviruses: academic interest or important basis for
      the development of vaccines and diagnostics?].
AB  - Pestiviruses cause economically important diseases of farm animals. Members of
      the Pestiviruses are bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, classical
      swine fever virus (CSFV) and border disease virus (BDV). Phylogenetic analyses
      based on the entire nucleic acid sequence encoding the Npro allow a statistically
      significant segregation of established species and of subgroups within the
      species. BVDV-1 strains isolated in Germany can be associated with at least five
      different subgroups. In contrast all BVDV-2 isolates detected in Germany so far
      are closely related, belonging to one subgroup. A group of virus isolates from
      sheep and zoo animals is clearly different from established pestivirus species
      and can be designated as BDV-2. Antigenetic relatedness of pestiviruses was
      studied using defined virus isolates and antisera in cross-neutralization assays.
      Six antigenic groups were distinguished corresponding to the genetic clusters
      BVDV-1, BVDV-2, CSFV, BDV-1, BDV-2 and Giraffe-1. A significant antigenic
      difference was also observed between members of subgroups 1a and 1b of BVDV-1.
      Studies on the genetic and antigenic heterogeneity of pestiviruses are important
      for the development of new vaccines, diagnostic tests and for eradication
      programs.

PMID- 12784554
TI  - [Conventional and marked BHV-1 vaccines in Germany: a brief review].
AB  - Since 1997 infections of cattle with bovine herpesvirus type 1 (BHV-1) are
      regulated by the German government with obligatory measures. Eradication of the
      virus is based on two different concepts: German federal states with a low BHV-1
      seroprevalence comply with a selection concept, that provides deletion of BHV-1
      positive cattle and only exceptional vaccination. States with a high BHV-1
      prevalence attempt to eradicate the virus using the marker concept. The marker
      concept is based on the vaccination with glycoprotein E (gE)-deleted marker
      vaccines and the accompanying serological differentiation between vaccinated and
      infected animals. This review deals with both, conventional and marked BHV-1
      vaccines, that are commercially available in Germany. Efficacy and safety of
      different inactivated vaccines and modified live vaccines have been evaluated in
      detail in several international experimental studies and field trials. Results of
      these studies are briefly reviewed and discussed in this article.

PMID- 12784556
TI  - [Perspectives on BVD eradication in Germany].
AB  - Infections with the bovine virus diarrhoea (BVD) virus are endemic with high
      seroprevalence in many countries of the European Union (EU). The significant
      economic damage caused by BVD infections has led to a paradigm shift with respect
      to a possible control. In some EU Member States control programmes have been
      initiated mostly on a voluntary basis and some compulsory. The most important
      element of all control efforts is the identification and removal of persistently
      infected (PI) animals. The subsequent steps depend on the respective
      seroprevalence and cattle density. Sweden was one of the first countries to
      introduce a national control program (1993), that is now being used as standard
      procedure in other countries. The starting position for the program was
      comparatively favorable since the country's cattle density is low and vaccination
      was not allowed. BVD infected herds were screened using a bulk milk ELISA and
      subsequently the PI animals in positive herds were identified and removed. The
      goal of the control program is the cattle population's certified freedom of BVD.
      The Scandinavian model is not applicable for most regions of Germany, since BVD
      virus prevalence and cattle density are unfavorably high. Here the primary goal
      is to minimize the economic losses caused by BVD and to lower the infective
      pressure. Therefore a Federal guideline was issued and some Federal States have
      provided additional regulations for compensation of PI animals and additional
      costs, respectively. Primary goal of the guideline is the eradication of PI
      animals and the systematic vaccination of all female offspring in order to avoid
      further economic damage and the emergence of new PI animals in case of re
      infection of the herd. Goal of this strategy is the BVD unsuspicious herd with a
      high immune status.

PMID- 12784557
TI  - [BVD diagnosis: an overview].
AB  - The first step and a crucial condition for the success of a control or
      eradication program for BVD (bovine viral diarrhea) is the identification and
      elimination of animals persistently infected with the virus. For this, besides
      detailed knowledge of the epidemiology, efficient diagnostic tests are necessary.
      This review summarizes the presently available diagnostic tests for detection of
      antibodies against the virus or for detection of viral components. Their
      performance and their applicability in eradication programs is discussed.

PMID- 12784558
TI  - [Elimination of persistently BVDV infect animals: efficient herd screening using
      RT-PCR and antigen ELISA in milk and serum samples].
AB  - With the long-term perspective of the eradication of BVD/MD in the German federal
      state Saxony-Anhalt a voluntary control program was initiated in 2002 by an
      administrative regulation based on federal German guidelines. The short-term aim
      of this program is the establishment of BVDV-unsuspected herds achieved by
      elimination of persistently infected cattle. The diagnostic program and
      particularly the choice of the diagnostic tools was based on the consideration of
      laboratory experiences as well as on economic and logistic aspects. A combination
      of RT-PCR and antigen-ELISA was found to be the suitable diagnostic methods. The
      screening started with examinations of sera pools using Real Time RT-PCR in the
      Light-Cylcer system. After positive pool results the individual persistently
      infected animals were detected using various commercial ERNS-antigen-ELISAs. The
      RT-PCR revealed a high degree of sensitivity and robustness. With respect to
      highly specific ELISAs the producers have to ensure the detection of all
      currently important virus strains. The prevalence of persistently infected
      animals in the cattle population of Saxony-Anhalt was about 0.2% during the last
      3 years. This is probably due to nearly 10 years of broad vaccination and will
      prove advantageous for BVDV elimination.

PMID- 12784559
TI  - [Antibody titer against bovine viral diarrhea virus (BVDV) in bulk milk samples
      from Bavaria].
AB  - A total of 5204 bulk milk samples were tested for antibodies against bovine viral
      diarrhea virus (BVDV) classified according to the scheme after Alenius. Forty
      five percent of the samples from 2002 were classified as class 0 and class 1, 55%
      as class 2 and 3. 6420 bulk milk samples from 1997 were classified in an
      independent study in 65.6% class 0 and 1 and 34.4% in class 2 and 3. In class 0
      and class 1 farms only very rarely persistent viremic animals have been found,
      whereas in class 2 and 3 their presence is highly likely. Our studies with non
      selected sera defined the serological screening of bulk milk samples as a
      promising tool for a possible BVDV eradication program in Bavaria.

PMID- 12784560
TI  - [Feasibility of serological bulk milk testing as a method for BVD surveillance].
AB  - A commercial ELISA detecting antibodies against bovine viral diarrhoea Virus
      (BVDV) was analysed for its applicability for bulk-milk screening. Detection
      limits were analysed using native and concentrated milk samples (milk treated
      with rennet and ammonium sulfate precipitated) from 10 cows whose sera showed
      different reactivity levels in the ELISA and from two cows which gave birth to
      persistently infected calves during the last year. Further this and a second
      commercial ELISA were used to screen 591 randomly selected bulk-milk samples. To
      clarify discrepancies thirty-nine herds were included in a follow-up study. A
      second bulk-milk sample and serum samples from 10 young cattle of 6 to 28 month
      of age per herd were analysed for antibodies against BVDV. The results of this
      second testing and the detection of viremic animals in 4 herds confirmed the
      results from initial bulk-milk testing with both tests. The analysed test is
      suitable for bulk-milk testing although its application is limited by
      vaccination.

PMID- 12784561
TI  - [Vaccines against infection with bovine viral diarrhea virus/mucosal disease
      (BVDV/MD): a short overview].
AB  - Various vaccine preparations against an infection with Bovine Viral Diarrhea
      Virus (BVDV) have been used since more than 30 years. To prevent reproduction
      failure and the generation of persistently infected animals, protection of
      heifers and cows against transplacental infection is the most important aim of
      BVDV vaccination. In principal, BVD vaccines with replication competent,
      attenuated BVDV (modified live vaccines) and vaccines with inactivated BVDV
      preparations (killed vaccines) are used. In Germany, modified live vaccines as
      well as killed vaccines are registered, however, only BVDV type I strains are
      included in both types of vaccines. This paper presents an short overview about
      the different BVD vaccines and their efficacy and safety. In addition, new
      vaccine types are mentioned and final conclusions are drawn.

PMID- 12784562
TI  - [Requirements for the use of ELISA systems in eradication programs].
AB  - Users of ELISA test systems applied in eradication schemes must be aware of their
      potential and their limitations. Means to improve laboratory quality as well as
      strict performance of the test procedure are essential. Sensitivity and
      specificity of test systems are limited. Therefore the establishment of a cascade
      of methods to verify questionable and positive results is important. Thus false
      positive results, which may threat the general acceptance of an eradication
      scheme, can be avoided.

PMID- 12784563
TI  - [Retrospective study of 200 cases of nasopharyngeal carcinoma].
AB  - Nasopharyngeal carcinoma is frequently diagnosed in advanced stages due to the
      anatomic characteristics of its site of origin and of the inspecificity of many
      of its clinical manifestations. However, cure rates are directly related with the
      early diagnosis. In this study of 200 patients affected by this tumor we analyse
      the different clinical manifestations, their chronology and their value as early
      indicators of nasopharyngeal tumour.

PMID- 12784564
TI  - [Paraganglioma of the vagus. A case report and review of literature].
AB  - The vagal nerve paraganglioma is a rare tumor over all the head and neck tumours.
      It presents with a insidious clinic, appearing usually as a asymptomatic
      laterocervical mass of low growth pattern. We present a case of a 53 years old
      woman with a left of painless laterocervical mass that produced cough with the
      palpation. We pretend to review the most relevant aspects of the diagnosis and
      treatment of the paraganglioma and therefore include this pathology in the
      differential diagnosis of laterocervical tumor.

PMID- 12784565
TI  - [Inverted papilloma of paranasal sinuses. Our experience of 15 cases. Review of
      literature].
AB  - Fifteen cases of nasosinusal inverted papilloma treated in our department from
      1994 to 2000 are reported. The most frequent initial symptom was unilateral nasal
      obstruction. Some others symptoms were rhinorrea, facial pain and self limited
      epistaxis. The most frequent surgical procedure performed was the paralateral
      rhinotomy with medial maxillectomy. The median average for the follow up was 28
      months, being diagnosed one recurrence. The paralateral rhinotomy with a medial
      maxillectomy, under functional endoscopic nasosinusal techniques are being more
      and more used, decreasing the indications of open techniques.

PMID- 12784566
TI  - [Diagnostic correlation between indirect laryngoscopy, fibro-laryngoscopy and
      microlaryngoscopy with the anatomopathological results].
AB  - We have studied 265 patients with an organical lesion of the larynx, using three
      different laryngoscopical methods: Indirect laryngoscopy, fibrolaryngoscopy and
      microlaryngoscopy. We have compared the correlation between each one and the
      anatomopatological diagnosis, concluding that microlaryngoscopy has the best
      correlation, better than the fibrolaryngoscopy and this one better than indirect
      laryngoscopy.

PMID- 12784567
TI  - [The use of scintigraphy and fine needle aspiration biopsy (FNAB) in thyroid
      surgery and review of literature].
AB  - Our aim is to know the usefulness of gammagraphy and FNAB (fine-needle aspiration
      biopsy) in thyroid surgery done in our ENT-Department during 12 years lapse. In
      this period of time are considered the outcomes of 461 thyroid gammagraphies and
      469 FNAB for diagnostic comparison with the final anatomopathological (AP)
      issues. We emphasize the 42.3% of cold nodules most of which (21.5%) were thyroid
      carcinomas (80.95% papillary Ca; 14.28% follicular Ca and the remainder medullary
      Ca). Between 319 folliculary proliferations according of FNAB only 17 were
      malignant tumours and when the aspiration puncture informed about positive
      malignant etiology (51 cases), 5 cases final diagnosis were benign pathology and
      the other 2 the pathology was of malignancy, but different to that of the initial
      diagnosis. We considerer that the sensibility of this test is about 86.28% in our
      series. Finally, our results are compared with those of other publications.

PMID- 12784568
TI  - [Laryngeal neurofibroma. A case report and literature review].
AB  - Neurofibroma is a rare pathology on the larynx. We distinguish two types of
      neurofibromas: plexiform and not plexiform in which the difference is at the
      cytoarchitectural level. The plexiform type is usually associated to the Von
      Recklinhausen disease, also know as neurofibromatosis type 1. They usually affect
      the supraglottic structure, and more frequently they are described in aritenoids,
      ariepiglottic folds, and posterior commissure. We present a case located at the
      glottic level of plexiform type, with a postsurgical follow-up of five years. We
      make a revision of the aethiopathogenesis, evolution and prognostic of these
      pathology in the bibliography.

PMID- 12784570
TI  - [Three cases of cell granular tumor of the larynx].
AB  - Cell Granular Tumor (CGT) are unusual tumors that can affect any site of the
      body, with most cases affecting the head and neck region. CGT of the larynx is an
      uncommon laryngeal tumor accounting for approximately 6-10% of the reported
      cases. In the larynx pseudoepitheliomatous hyperplasia may predispose to confuse
      the CGT with frothy (squamous) cell carcinoma. The origin of this tumor is a
      matter of debate but most authors believe it to be neural in origin.

PMID- 12784569
TI  - [Recurrent respiratory papillomatosis. Our experience and literature review].
AB  - The recurrent respiratory papillomatosis is a benign lesion induced by virus,
      with predisposal factors not yet clear out. Several treatment have been used,
      being the endoscopic surgery with laser CO2 the most used technique. We present
      our experience with laryngeal papillomatosis patients operated with laser CO2 in
      the last 15 years. The high rate of recidive in the youth pattern and the
      possibility of malignant degeneration in the adults charactherises this patients.
      Meanwhile without not other concluyent works surgery will be the first
      therapeutic alternative, avoiding mutilant operations, and paying attention in
      detecting lesions suggesting malignancy.

PMID- 12784571
TI  - [Frontal-lateral laryngectomy].
AB  - We present our series of 21 patients treated since 1991 to 2000 with glottic
      carcinomas T1a-b with commissure extension. The surgical technique used has been
      frontolateral laryngectomy as Leroux-Robert in 8 cases, and in the other 13 cases
      we have contributed with somme variations using a piece of superficial cervical
      fascia to close the thyroid opening and a piece of the vestibular band for the
      reconstruction at the glottic level. We studied the functional and oncological
      results we have obtained with a minimum control of one year and maximum of seven
      years.

PMID- 12784573
TI  - Psammomatoid ossifying fibroma of the ethmoid.
AB  - We present a 16 year-old girl who suffered since one year of a painless slow
      growing mass on the left medial orbital rim causing globe displacement. CT-scan
      and MRI of the orbit with T1 and T2 weighted images showed the presence of a
      large mucocoele in the frontal sinus. This occurred secondary to the obstruction
      of the sinonasal tract by a bony tumour. Histopathology showed a lesion
      consisting of fibrous tissue and ossicles or psammomatoid bodies. The diagnosis
      of a psammomatoid ossifying fibroma (POF) was made.

PMID- 12784572
TI  - [Retropharyngeal phlegmon in the adult. Presentation of a case].
AB  - Nowadays retropharyngeal phlegmon and abscesses are uncommon. Advances in medical
      care have changed the morbidity and mortality of this processes. The advance of
      computed tomography (CT) has made possible a more exact diagnosis of these
      infections. If CT suggests a cellulitis medical treatment is used, but abscesses
      need surgical drainnage.

PMID- 12784574
TI  - [Solitary retinal astrocytic hamartoma simulating retinoblastoma].
AB  - Retinal astrocytic hamartoma and retinoblastoma may be very similar clinically
      and their differentiation in atypical cases can be difficult, even with the use
      of ultrasonography and computed tomography. In such cases, a close follow-up is
      recommended before enucleation. This paper reviews the case of a 18 month old
      girl who presented with a solitary retinal astrocytoma of the right eye, without
      any other physical or ocular disorder. The initial presentation simulated a
      retinoblastoma; nevertheless atypical patterns as yellow calcifications and the
      lack of tortuous and dilated feeding blood vessels were present. Ophthalmoscopic
      and ultrasound regular evaluation did not reveal any change after one year follow
      up. Additional investigations performed in order to exclude tuberous sclerosis
      (neurological and dermatological examination, CT-scans) showed no other organ
      involvement, which ruled out a phakomatosis. The clinical appearance and course
      of astrocytic hamartomas, its differential diagnosis from other retinal tumors,
      especially retinoblastoma, and its association with tuberous sclerosis are
      discussed.

PMID- 12784575
TI  - Epidemiological typing of Acanthamoeba strains isolated from keratitis cases in
      Belgium.
AB  - From the corneas of nine keratitis patients and from their contact lenses,
      contact lens boxes and saline solutions, 15 strains of Acanthamoeba have been
      isolated. An Acanthamoeba strain was isolated from the swimming pool where one of
      the patients swam, while in the tapwater of the houses of three patients
      investigated, no Acanthamoeba could be detected. All the Acanthamoeba isolates
      from the cornea belong to genotype T4, but are different subtypes of T4. The
      Acanthamoeba detected on the contact lenses (and/or associated paraphernalia) of
      a patient are of the same subtype as that isolated from the cornea. The only
      Acanthamoeba strain isolated from a contact lens which was not related to an
      Acanthamoeba keratitis infection proved to be another genotype. A strain of
      Hartmannella from a cornea and two vahlkampfiids isolated from contact lenses had
      no connection with keratitis. This study confirms that, as found elsewhere, only
      Acanthamoeba genotype T4 of the 12 known Acanthamoeba genotypes is responsible
      for keratitis in Belgium. Most cases of Acanthamoeba keratitis cases are due to
      poor hygiene in the treatment (cleaning and storage) of contact lenses.

PMID- 12784576
TI  - Incidence, perinatal risk factors, visual outcome and management of threshold
      retinopathy.
AB  - The incidence of threshold retinopathy, clinical characteristics and risk factors
      to develop threshold retinopathy are described in a group of preterm infants
      admitted between 1996 and 2000 in a single tertiary neonatal intensive care unit.
      A subset of these infants (n = 31) developed threshold retinopathy (ROP).
      Incidence of threshold ROP in survivors with a birth weight below 1500 g is 6.4%.
      Pre-, peri- and postnatal characteristics of these infants are described and
      compared with matched controls of the same gestational age (GA) and admitted in
      the same unit in an attempt to focus on relevant risk factors of threshold ROP.
      We also report on visual outcome data in infants who developed threshold
      retinopathy. Finally, we describe our experience with perioperative management in
      this cohort.

PMID- 12784577
TI  - Nonglaucomatous optic disk atrophy and excavation in the elderly.
AB  - The causes of nonglaucomatous optic disk atrophy and excavation are enumerated in
      people 65 years or older: congenital anomalies, myopia, ischemic disorders,
      transsynaptic degeneration, traumatic, compressive, hereditary, toxic and
      infectious optic neuropathy.

PMID- 12784578
TI  - [Assessment of nonpenetrating deep sclerectomy with reticulated hyaluronic acid
      implant SKGEL and/or preoperative application of 5-luorouracil: results of 2 and
      a half years].
AB  - PURPOSE: To assess the effectiveness and the safety of deep sclerectomy (DS) with
      reticulated hyaluronic acid implant (SKGEL) and/or 5-Fluorouracile (5-FU).
      MATERIAL-METHODS: 42 phakic eyes (42 patients) (mean age: 61.0 +/- 11.5 years)
      with medically uncontrolled open angle glaucoma and without history of previous
      filtering procedure were included in this non-randomized retrospective study.
      According to the peroperative protocol, the patients were categorized into 3
      groups: DS + SKGEL (7 eyes), DS + 5-FU (50/mg/ml during 3 minutes) (13 eyes) and
      group C with SKGEL and 5-FU simultaneously (22 eyes). RESULTS: The mean follow up
      was 30.6 +/- 9.2 months and was significantly shorter in group C. The 3 groups
      were comparable with respect to the age of the patients, the severity of
      glaucomatous defects, the distribution of the target IOP, the mean number and
      duration of preoperative medications as well as to the mean preoperative visual
      acuity and IOP. The mean IOP was significantly decreased from 27.3 +/- 3.2 mm Hg
      to 16.1 +/- 3.7 3.7 mm Hg (p < 0.0001) and was not significantly different
      between the 3 groups at 24 months follow up (p > 0.05). Mean visual acuity was
      not significantly altered in the 3 groups (p > 0.05). Complete (target IOP
      reached without medication or YAG laser goniopuncture) and qualified (target IOP
      reached with medication and/or YAG laser goniopuncture) final success rates were
      respectively 33.3% and 83.3%. The frequency of distribution of success was not
      significantly different between the 3 groups but the percentage of success was
      100% in group A, 84.6% in group B and 77.2% in group C. Subconjunctival
      injections were needed in 33% in the first postoperative month. (group A: 28.5%;
      group B: 46.2%; group C: 27.2%) (X2 p > 0.05). Postoperative complications were
      relatively minor and were observed in 66% (P > 0.05 between the 3 groups). YAG
      laser goniopunctures were performed in 38% (group A: 16.6%; group B: 61.5%;
      group: 33.3%, X2 p > 0.05). Complete and qualified success probability were
      better in SKGEL group comparatively with the other 2 groups. CONCLUSIONS:
      Considering its limitations and with a follow-up of 2 years and half, this study
      could confirm the safety and the efficacy of DS in return for which topical
      medication(s) and/or YAG laser gonioperforations were needed in a relatively high
      percentage of the cases. The benefits of the SKGEL implant on the quality of the
      IOP control appeared to be higher than 5-FU.

PMID- 12784579
TI  - New insights into the subjective perception of visual field defects.
AB  - Most glaucoma patients are unaware of their visual problem until a late stage of
      the disease, probably because their visual field defects are being filled-in by
      the brain. According to new insights into how our brain works, plasticity of the
      visual cortex allows the brain to reorganize after damage to the retina or the
      visual pathways. This plasticity involves activation of existing but normally
      ineffective synapses, in a highly organized system of long-range horizontal
      connections in the visual cortex. Normal cells in the cortex surrounding the
      lesion thus take control of the deprived ones. As a result, glaucomatous field
      defects are probably concealed in the colors and patterns of the surround, up to
      the point where visual input has decreased to such an extent that the brain is
      not able anymore to compose a plausible image.

PMID- 12784580
TI  - [Preliminary results for treatment of rhegmatogenous retinal detachment and new
      material for episcleral buckle: silicone Korobelnik sponge].
AB  - In order to evaluate the efficacy and short-term tolerance of the Korobelnik
      sponge in the primary treatment of uncomplicated rhegmatogenous retinal
      detachments (RRD), a retrospective study dealing with the first 30 consecutive
      cases of RRD primarily operated on with the use of this Korobelnik sponge is
      undertaken. Primary anatomical success is obtained in 80% of the cases (24/30),
      with a mean postoperative follow-up of 3.1 months. Conjunctival inflammation or
      dehiscence are not observed. Two sponges have to be removed for unrelated
      reasons. The study shows that the Korobelnik sponge is a reliable and well
      tolerated buckling material, at least in the short term.

PMID- 12784581
TI  - [Superior oblique myokymia secondary to neurovascular compression].
AB  - In a patient with superior oblique myokymia, a contact is visualised between the
      right trochlear nerve and a vascular structure by high resolution thin slices
      magnetic resonance images coupled to angio-MR. A similar contact is not
      visualised on the left side. This suggests that the neuro-vascular contact is the
      cause of this superior oblique myokymia and offers the possibility of neuro
      surgical decompression if necessary.

PMID- 12784582
TI  - Biological characterization of experimental carbon samples.
AB  - The use of carbon is widespread in fields as wide as aeronautics, cars,
      electricity or electronics. The biomedical applications of carbon are also
      numerous. The purpose of our work is to test four experimental carbon fibers (A,
      B, C and D; B being the negative control) to determine the best clinical
      application. Four tests of cytocompatibility are carried out (cell viability,
      inflammatory test, cell proliferation and cell morphology). Two different cell
      lines are used: the L132 cell line (epithelial embryonic pulmonary human cell)
      and the HaCaT line (human normal spontaneously immortalized skin keratinocytes).
      The results of the biological tests are compared with those of a carbon fiber
      sample already marketed as a bandage in the treatment of infected wounds:
      Actisorb "Plus (J2). The various tests show us that only two experimental samples
      are slightly cytotoxic (A, D). On the other hand, no sample supports cell
      adherence. A, B, C and D do not have an inflammatory effect. J2 appears at the
      same time cytotoxic and inflammatory. Consequently, being given the physical
      presentation and the biological properties of experimental samples (A, C and D),
      we intend them for an application in the field of wound healing, as a bandage.
      Also further experimentation is needed.

PMID- 12784583
TI  - Verification of the symmetry of the mandibular ramus in patients with
      temporomandibular disorders and asymptomatic individuals: a comparative study.
AB  - Some studies have reported that mandibular ramus asymmetries are more pronounced
      in patients with temporomandibular disorders. The symmetry of the mandibular
      ramus was verified in a group of patients with temporomandibular disorders and
      compared with that of a control group of asymptomatic individuals. Heights of the
      mandibular ramus and of the condyle and gonial angles were measured from
      panoramic radiographs. In the comparison of numerical values between dysfunction
      and asymptomatic groups there was no significant difference; when comparing sides
      within each group, there was a significant difference in gonial angle in the
      asymptomatic group. Using the formula: (R-L)/(R+L) x 100%, in the comparison
      between groups, there was a significant difference as to condylar height. With a
      subdivision in each group, having the value of 3% to calculated symmetry as a
      reference, there was no significant difference between groups. Comparing gender
      or age intervals in both groups, there was no significant difference. It was
      concluded that there was significant difference in calculated symmetry only as to
      condylar height between disorder patients and asymptomatic individuals.

PMID- 12784584
TI  - Cytoskeletal and membrane bound antigens in human oral normal and malignant
      keratinocytes: an intensity of staining analysis.
AB  - In this study, we tested the hypothesis that a significant difference exists in
      the integrated optical density (IOD) of membrane and cytoplasmic antigens in
      monolayer keratinocytes cultures. Oral normal and two malignant (SCC15 and SCC25)
      keratinocyte cultures were stained with antibodies specific for E-cadherin, beta
      catenin, beta-1 integrin, cytokeratin (CK) 14, CK19, CK10/11 and involucrin. The
      IOD recorded (n = 12) was analyzed for significant differences using a two-way
      analysis of variance (significance level set at alpha = 0.05); antibodies and
      cell cultures were grouped according to Tukey's Group Comparison post-test. The
      majority of normal cell cultures exhibited E-cadherin, beta-catenin, involucrin
      and beta-1 integrin IOD values significantly higher than the two SCC cell lines.
      No definite staining pattern distinguished normal and malignant cells in relation
      to cytokeratins 14, 19 and 10/11. Our observations suggest that IOD measures
      constitute a good predictor of antigen steady state levels in monolayer cell
      cultures. According to these observations, SCC cell lines and normal cells appear
      to differ in the expression of E-cadherin, beta-catenin, beta-1 integrin and
      involucrin, although some variability within normal cells can also be observed.

PMID- 12784585
TI  - [State of the art: posture and occlusion].
AB  - The Authors of this work propose to give an evaluation about actual relationship
      between posture and occlusion, trying of to give some indications about posture's
      meaning, organizing the relation about five points: Posture's definition
      Posture's history Posture's models of study Occlusal support en posture
      Diagnostic procedures.

PMID- 12784586
TI  - Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism
      as a predictive marker for Iranian dyspeptic patients.
AB  - Helicobacter pylori infects the majority of the population in the developing
      countries. However, the rate of gastrointestinal complications such as peptic
      ulcers and gastric malignancies has no parallel with the infection. In order to
      determine whether cytotoxin (vacA) and its allelic polymorphism can serve as
      screening markers for such a population, H. pylori strains were isolated from one
      hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted
      and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the
      signal sequence region of the vacA gene identified 68% (70 out of 103) of
      patients with non ulcer dyspepsia (NUD) and 79% (23 out of 29) of the patients
      with peptic ulcer disease (PUD) possessing the s1 genotype. S1 strains were
      significantly more prevalent among patients with PUD as compared to the NUD (p <
      0.05). In regard to the middle region, 55% of the patient isolates belonged to
      the m2 genotype with no correlation to disease. The s1m2 genotype was the most
      prevalent among all patients and significantly correlated with the PUD group (p <
      0.05).

PMID- 12784587
TI  - [Biology of man-mosquito Plasmodium transmission].
AB  - The transmission of Plasmodium is a complex process that requires the encounter
      of three organisms: the parasite, the host and the mosquito vector. For a better
      understanding, the transmission of this parasite can be divided in four cyclical
      steps: 1) the development in man, including gametocytogenesis, 2) the transfer
      from man to mosquito, 3) the sporogonic development in the mosquito, 4) the
      transfer from mosquito to man. The present article proposes a review of these
      different aspects and focuses especially to recent biological knowledge on
      Plasmodium falciparum in the gametocytogenesis issues, infectivity of
      gametocytes, sporogonic development and natural factors limiting this
      development.

PMID- 12784588
TI  - [Four first Congolese cases of pelvic ankylosing spondylitis].
AB  - The authors report four ankylosing spondylitis cases observed within 11 years
      (1990-2000) of rheumatologic exercise among 10,000 patients examined in
      consultation and hospitalization at Brazzaville university teaching hospital. It
      confirms that ankylosing spondylitis is a rare disease in sub-Saharan black
      Africa.

PMID- 12784589
TI  - [Evaluation of Antilles fish ciguatoxicity by mouse and chick bioassays].
AB  - Ciguatera is a common seafood poisoning in Western Atlantic and French West
      Indies. Ciguatera fish poisoning in the Caribbean is a public health problem. A
      toxicological study was carried out on 178 Caribbean fish specimens (26 species)
      captured off Guadeloupe and Saint Barthelemy between 1993 and 1999. The mouse
      bioassay and the chick feeding test were used to control fish edibility.
      Ciguatoxins presence was assumed when symptomatology was typical of ciguatera in
      mouse and chick. Fishes were classified in three groups: non toxic fish (edible),
      low toxic fish (not edible) and toxic fish (not edible). 75% of fishes were non
      toxic. Toxic fish specimens belonged to four families of high trophic level
      carnivores: Carangidae, Lutjanidae, Serranidae et Sphyraenidae. Percentages of
      toxic fishes to humans reached 55% for Caranx latus and 33% for Caranx
      bartholomaei and Caranx lugubris. Only a significant correlation between weight
      and toxicity was only found for C. latus and snappers. Small carnivorous groupers
      (Serranidae) were also toxic. Atoxic fish species were (a) pelagic fish
      (Coryphaena hippurus, Auxis thazard and Euthynnus pelamis), (b) invertebrates
      feeders (Malacanthus plumieri, Balistes vetula), (c) small high-risk fish or (d)
      fish of edible benthic fish families. Liver of four fishes (Mycteroperca
      venenosa, Caranx bartholomaei, Seriola rivoliana, Gymnothorax funebris) contained
      ciguatoxins at a significant level although their flesh was safe. This study
      confirms the usefulness of mouse and chick bioassays for sanitary control of
      fish.

PMID- 12784591
TI  - [Application of the Unmet Obstetrical Needs method in the III neighborhood of
      Niamey, Niger (1999)].
AB  - West Africa has probably the highest levels of maternal mortality in the world. A
      new method has been developed by the Institute of Tropical Medicine of Antwerp
      (Belgium) that gives an estimate of the Uncovered Obstetrical Need. This
      technique tested in different Western African countries has been now evaluated
      also in an urban medical district in Niamey, capital of Niger, for the year 1999.
      The uncovered obstetrical need has been estimated at 15 major Obstetrical
      Interventions for this period; this means that 15 pregnant women didn't undergo a
      major surgical intervention necessary to save their life and that they probably
      died because of this non-intervention. We met quite a lot of problems with this
      new method: (i) the first problem is related to the difficulty to obtain correct
      demographic information: it is very difficult to estimate population growth in
      urban african areas, present population and number of attended births. (ii) The
      second difficulty came from sociocultural habits: primipare women in Niger go
      back to their family to deliver (and the place where their family lives is not
      necessarily the same as the place where they stay with their husband); it is
      quite possible that a number of primipare women needing a major surgical
      intervention didn't undergo this intervention because they delivered in their
      home village (and perhaps died there). (iii) At last, the estimation of a
      reference rate (calculated at 0.9% for Niger) implies that all women needing a
      major obstetrical intervention in Niamey, and having a theoretical easy access to
      medical infrastructures (first line as second line hospitals) present themselves
      when having a major obstetrical problem. This is probably "wishful thinking". The
      interest of this new method lies in the fact that it is a cheap technique and
      easy to put into practice ... provided that one disposes of medical
      infrastructures that collect correctly all necessary medical information.

PMID- 12784590
TI  - [In vivo evaluation of chloroquine therapeutic efficacy in uncomplicated
      Plasmodium falciparum malaria in Central African Republic ine 1997 and 1998].
AB  - The efficacy of oral chloroquine was assessed in 268 children aged from 6 to 59
      months attending pediatric services in regional hospitals between September 1997
      and December 1998, located in the five county towns of the sanitary regions of
      the Central African Republic. Chloroquine was prescribed at 25 mg per kg body
      weight, and administered over 3 days to patients suffering from uncomplicated
      malaria. Body temperature and blood smears including parasitaemia were recorded
      on days 0, 3, 7 and 14. The main objective of the present study was to evaluate
      the therapeutic efficacy of chloroquine in the treatment of uncomplicated malaria
      using in vivo tests according to the WHO protocol (1996). The secondary objective
      was to identify the predictive factors of chloroquine relapses. Early relapses
      rates were under 15% except in Bangui (40%). A recurrence of parasitaemia with
      fever, sign of late relapse, was noted in 9% of children in Bambari, 9% in
      Bangassou, 8% in Bangui, 5% in Bossangoa and 4% in Berberati. The rate of
      successfully treated patients was between 66% and 75% except in Bangui (36%).
      Only the places of study and anaemia in days 0 were significant predictive
      factors of therapeutic relapses. Since the emergence of chloroquine resistance
      cases to P. falciparum in 1983 in Central African Republic, the phenomenon has
      increased. According to our results, a strong chloroquine resistance appears in
      the capital Bangui. Therefore, chloroquine should be replaced there for the first
      line treatment of uncomplicated P. falciparum malaria. In the provinces, it
      doesn't seem necessary to change the current chloroquine-based first line
      treatment.

PMID- 12784592
TI  - [Antitubercular drug treatment failure and HIV infection in Abidjan (Ivory
      Coast)].
AB  - A retrospective study from 1989 to 1993 was carried out on eighty patients out of
      106 cases of tuberculosis treatment failure; representing 2.2% of persons with
      active pulmonary tuberculosis followed at the tuberculosis screening center of
      Abidjan. The rate of HIV seropositivity was 43.7%. At the beginning of the
      therapy, 80% of HIV-positive and 89% of HIV-negative had diffuse pulmonary
      lesions (no significant difference: P > 0.05. At the end of second month therapy,
      49% of co-infected and 51% of HIV-negative patients showed bacteriological
      negative sputum. The treatment administered after reporting failure, led to 63%
      of recovery among the HIV-positive (22/35) and 62% among the HIV-negative
      (28/45). On the other hand, the rate of patients out of touch was high in both
      populations; respectively 29% of HIV infected and 31% of HIV-negative spreading
      the risk of contamination of neighbourhood by probably resistant bacilli.

PMID- 12784593
TI  - [Intestinal parasitoses in the Mahajanga region, west coast of Madagascar].
AB  - A study on human intestinal parasites was carried out from November 1996 until
      January 1997, in Mahajanga's hospital, on the western coast of Madagascar. We
      collected the faeces from 401 patients and the sera from 112 of them. Faecal
      examination using direct examination and MIF method revealed that 67.6% of the
      stools contained at least one parasite. The frequency of the protozoa was high
      (47.7%). The prevalence of the nematodosis reached 23.4%. Hymenolepis nana,
      Taenia saginata or solium and Schistosoma mansoni were less frequent
      (respectively 2.5%, 0.75% and 3.7%). More than 50% of the sera contained
      antibodies anti-Ascaris lumbricoides and anti-Strongyloides stercoralis. Serology
      by IFI using Schistosoma antigen was positive in 15.2% of the cases. The
      serological and microscopical exams showed that Entamoeba histolytica was present
      in this region and that amoebiasis should be considered as one of the etiologies
      of diarrhoea. The study pointed out also the frequency of the transmitted fecal
      infections. Preventive measures as water distribution, sanitary installations,
      hygiene education should be implemented.

PMID- 12784594
TI  - [Serological study of toxoplasmosis in Vietnam in a population of drug users (Ho
      Chi Minh city) and pregnant women (Nha Trang)].
AB  - Toxoplasmosis is a neglected disease in Vietnam particularly in populations with
      a high risk of developing complications. The seroprevalence of Toxoplasma gondii
      was calculated by testing blood samples for Toxoplasma specifically
      immunoglobulin G and immunoglobulin M on 300 intravascular drug users and on 300
      pregnant women. Among intravascular drug users, the seroprevalence of IgG and IgM
      was 7.7% and 0.08%, respectively. In pregnant women the prevalence of anti
      toxoplasmosis IgG and IgM was respectively 11.2% and 0%. 0.28% of all estimated
      pregnancies in Vietnam are affected with toxoplasmosis, i.e. around 4800
      pregnancies per year. In conclusion, a screening of Toxoplasma infections should
      be recommended in HIV/AIDS patients.

PMID- 12784595
TI  - EBRI research highlights: health benefits.
AB  - The Employee Benefit Research Institute (EBRI) is a nonpartisan, nonprofit public
      policy research organization based in Washington, DC, that has been researching
      economic security issues for almost 25 years. Founded in 1978, its mission is to
      contribute to, encourage, and enhance the development of sound employee benefit
      programs and sound public policy through objective research and education. EBRI
      does not lobby and does not take positions on legislative proposals. EBRI
      receives funding from individuals, employers of all types, unions, foundations,
      and government. EBRI's research work has focused on retirement- and health
      related issues, particularly involving pension/retirement plan coverage and
      health insurance coverage in the employment-based benefits system. EBRI is a
      major source of unbiased data on the uninsured and current trends involving
      401(k), IRA, and traditional pension-type retirement plans. EBRI research
      programs also include economic modeling of Social Security reform proposals and
      development of the EBRI/ICI 401(k) database, the largest and most detailed of its
      kind. This EBRI Special Report/Issue Brief (May 2003) synthesizes highlights of
      recent EBRI research on health issues. The next Issue Brief (June 2003) will
      present recent EBRI research on retirement benefits. It should be stressed that
      this document contains only highlights of EBRI's collection of research and
      analysis; for greater detail and information, visit EBRI's Web site
      (www.ebri.org) or contact EBRI directly.

PMID- 12784596
TI  - Research must be seen to be free of academic and market pressures.

PMID- 12784597
TI  - Research fraud: issues of which practitioners should be aware.
AB  - Treatment and care given to patients should be evidence-based, but research
      results based on fraudulent findings can have a serious impact on care. This
      paper examines how fraud may be perpetuated and discusses standards for robust
      research.

PMID- 12784598
TI  - Medical journal editors' uniform requirements for manuscripts submitted to
      biomedical journals.
AB  - These guidelines on publishing manuscripts in medical journals were drawn up by
      the International Committee of Medical Journal Editors. They outline a number of
      principles that protect patients and ensure that work is ethical and honest.

PMID- 12784599
TI  - Identifying the causes of increased wound pain: the role of the tissue viability
      nurse.
AB  - A leg ulcer that had stopped healing was causing a patient increased pain. Heavy
      infection was identified as the cause, and found to be exacerbated by a range of
      factors. An assessment resulted in treatment changes, leading to complete
      healing.

PMID- 12784600
TI  - Short-stretch compression bandages and the foot pump: their relationship to
      restricted mobility.
AB  - Practitioners are generally advised not to use short-stretch bandages on patients
      who are immobile. But this appears to reflect confusion about calf muscle
      function, which research indicates still occurs during periods of limited
      mobility.

PMID- 12784601
TI  - Wound measurement: can it help us to monitor progression to healing?
AB  - Wound measurement can help practitioners to monitor the progression to healing.
      The most effective way of doing this is to calculate the percentage reduction of
      wound area over time, particularly within the first four weeks.

PMID- 12784602
TI  - Errors and discrepancies: a patient perspective on leg ulcer treatment at home.
AB  - OBJECTIVE: This Norwegian study explored the treatment experiences of nine
      patients with a leg ulcer who lived at home. METHOD: The study was descriptive
      and exploratory, with open-ended interviews. Five women and four men aged 60-96
      years who had a leg ulcer for more than six weeks participated. Most had a
      venous/arterial leg ulcer, lasting from between four months to 'my whole adult
      life'. RESULTS: Treatment was not always carried out in a correct and caring
      manner. The patients experienced trial and error in their treatment, delays in
      the arrival of the helpers, unhygienic methods and lack of information about the
      cause and treatment of their ulcer. Despite these problems, they had confidence
      in the treatment they received. CONCLUSION: The treatment, hygiene and
      organisation of the care of patients with leg ulcers living at home needs
      improving.

PMID- 12784603
TI  - Cloning, expression, and characterization of an antifungal chitinase from
      Leucaena leucocephala de Wit.
AB  - Chitinase cDNAs from Leucaena leucocephala seedlings were cloned by PCR
      amplification with degenerate primers based on conserved class I chitinase
      sequences and cDNA library screening. Two closely related chitinase cDNAs were
      sequenced and inferred to encode precursor proteins of 323 (KB1) and 326 (KB2)
      amino acids. Expression of the KB2 chitinase from a pET32a plasmid in Origami
      (DE3) Escherichia coli produced high chitinase activity in the cell lysate. The
      recombinant thioredoxin fusion protein was purified and cleaved to yield a 32-kDa
      chitinase. The recombinant chitinase hydrolyzed colloidal chitin with
      endochitinase-type activity. It also inhibited growth of 13 of the 14 fungal
      strains tested.

PMID- 12784604
TI  - Properties of rice cooked with commercial water-soluble soybean polysaccharides
      extracted under weakly acidic conditions from soybean cotyledons.
AB  - It has been found that commercial water-soluble soybean polysaccharides (SSPS)
      can make cooked rice and noodles non-sticky and prevent rice grains and noodles
      from adhering to each other. We studied in detail the phenomenon of rice cooked
      with SSPS. We assumed that the phenomenon resulted from the interaction between
      SSPS and starch during cooking, and studied the effects of SSPS on the
      gelatinizing behavior of rice starch by using a Rapid-Visco-Analyzer. The
      addition of SSPS reduced the viscosity of the gelatinized starch. This lower
      final viscosity of the rice starch was more distinct from than that of potato
      starch. These results imply that the properties of SSPS in forming a non-sticky
      condition might result from a decrease in the viscosity of the gelatinized
      starch.

PMID- 12784605
TI  - Formate-stimulated oxidation of methanol by Pseudomonas putida 9816.
AB  - It has been reported that Pseudomonas putida 9816 is able to grow on methanol,
      but it does not have methanol dehydrogenase or oxidase activity. To utilize
      methanol it requires yeast extract. The utilization of methanol can be
      accelerated by adding formate, which obviously helps oxidize methanol and win
      biologically useful energy. This pseudo-oxidation is catalyzed by a reverse
      formaldehyde dismutase. Thus, methanol can be both assimilated and dissimilated.
      Formate alone cannot replace yeast extract. The strain is auxotrophic.

PMID- 12784606
TI  - Characterization of factors involved in the production of 2(E)-nonenal during
      mashing.
AB  - To characterize the factors involved in the production of volatile aldehydes
      during mashing, a model mashing experiment was done. After we inactivated the
      endogenous lipoxygenase (LOX) activity in the mash by mashing at 70 degrees C for
      30 min, further incubation with recombinant barley LOX-1 stimulated the
      accumulation of 2(E)-nonenal; however, this effect was significantly reduced by
      boiling the mash sample. The result suggests that both LOX-1 and a heat-stable
      enzymatic factor are involved in the production of 2(E)-nonenal during mashing.
      Malt contained fatty acid hydroperoxide lyase-like activity (HPL-like activity)
      that transformed 9-hydroperoxy-10(E), 12(Z)-octadecadienoic and 13-hydroperoxy
      9(Z), 11(E)-octadecadienoic acid into 2(E)-nonenal and hexanal, respectively.
      Proteinase K sensitivity tests showed that they are distinct factors. 9-HPL-like
      activity survived through the mashing at 70 degrees C for 30 min but was
      inactivated by boiling, suggesting it will be the heat-stable enzymatic factor
      found in the model mashing experiment.

PMID- 12784607
TI  - Ribonuclease inhibitors in Malus x domestica (common apple): isolation and
      partial characterization.
AB  - A ribonuclease inhibitory activity was detected in the fruits of common apple,
      Malus x domestica, cv. Fuji, and purified by affinity chromatography on
      ribonuclease A-Sepharose. It inhibited hydrolysis of cyclic-2':3'-CMP by bovine
      pancreatic ribonuclease A with an apparent inhibition constant of about 5 x 10(
      8) M. Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry of the purified protein gave two peaks corresponding to the mass
      numbers of 55,658 and 62,839, while three bands of 43-, 34-, and 21-kDa were
      detected by SDS-PAGE. These results suggested that the inhibitor preparation was
      a mixture of two proteins comprised of 43- and 21-kDa subunits or of 34- and 21
      kDa subunits. Attempts to separate these two proteins were unsuccessful. Amino
      acid composition and N-terminal amino acid sequence of these subunits were also
      identified and N-terminal sequences showed some similarity to that of cottonseed
      storage globulin. The significance of the presence of ribonuclease inhibitors in
      apple fruits is not clear, but it might allow some speculation about their
      possible involvement in the control of the self-incompatibility ribonuclease of
      Rosaceae plants.

PMID- 12784608
TI  - Gene cloning and functional analysis of a second delta 6-fatty acid desaturase
      from an arachidonic acid-producing Mortierella fungus.
AB  - We demonstrated that Mortierella alpina 1S-4 has two delta 6-desaturases, which
      are involved in the desaturation of linoleic acid to gamma-linolenic acid. For
      one of the two delta 6-desaturases, designated as delta 6I, gene cloning and its
      heterologous expression in a fungus, Aspergillus oryzae, has previously been
      reported. In addition, we indicated in this paper that there is an isozyme of the
      two delta 6-desaturases, designated as delta 6II, in M. alpina 1S-4. The
      predicted amino acid sequences of the Mortierella delta 6-desaturases were
      similar to those of ones from other organisms, i.e. borage and Caenorhabditis
      elegans, and had a cytochrome b5-like domain at the N-terminus, being different
      from the yeast delta 9-desaturase, which has the corresponding domain at the C
      terminus. The full-length delta 6II cDNA was expressed in A. oryzae, resulting in
      the accumulation of gamma-linolenic acid (which was not detected in the control
      Aspergillus) up to 37% of the total fatty acids. The analysis of real-time
      quantitative PCR (RTQ-PCR) showed that the quantity of delta 6I RNA was 2.4-, 9-,
      and 17-fold higher than that of delta 6II RNA on 2, 3, and 4 days in M. alpina 1S
      4, respectively. M. alpina 1S-4 is the first fungus to be confirmed to have two
      functional delta 6-desaturase genes.

PMID- 12784609
TI  - Localization of T cell epitope regions of chicken ovomucoid recognized by mice.
AB  - We localized the T cell epitope regions of chicken ovomucoid (OVM), a potent egg
      allergen, with the overlapping pin-peptides covering the entire sequence of OVM
      and three strains of mice with different haplotypes. In C3H/He (H-2k) mice, the T
      cells recognized relatively broad regions on OVM; the dominant regions were 49-93
      and 97-114 residues, and the subdominant regions were 7-21, 37-48, 94-96, 115-123
      and 145-177 residues. In contrast, a more limited number of T cell epitope
      regions were localized in BALB/c (H-2d) and C57BL/6 (H-2b) mice. The T cells from
      BALB/c mice recognized 100-114 and 157-171 residues, and the T cells from C57BL/6
      mice recognized only 157-180 residues. These results were confirmed by using
      peptides separately synthesized and purified on the putative epitope regions. The
      roles of the carbohydrate moieties and cysteine residues involved in the
      disulfide bridges of OVM were also examined, and we found that they were not
      important in recognition by the T cell/antigen presenting cell.

PMID- 12784610
TI  - Purification and characterization of formate dehydrogenase from Ancylobacter
      aquaticus strain KNK607M, and cloning of the gene.
AB  - Ancylobacter aquaticus strain KNK607M, which had high NAD-dependent formate
      dehydrogenase (FDH) activity, was newly isolated. The enzyme, purified to
      homogeneity, was a dimer composed of identical subunits with a molecular mass of
      44 kDa. The specific activity was 9.5 u/mg, and the enzyme was optimum at pH 6.3
      and 50 degrees C, most stable at pH 7.0, and stable at 50 degrees C or lower. The
      apparent Km values for formate and NAD+ were 2.4 and 0.057 mM, respectively. The
      enzyme was specific to formate and was inhibited by SH reagents and heavy metal
      ions. The cloned gene of FDH contained one open reading frame (ORF) of 1206 base
      pairs, predicted to encode a polypeptide of 401 amino acids, with a calculated
      molecular weight of 43,895; this gene was highly expressed in E. coli cells. The
      FDH had high identity to other FDHs, i.e., those of Pseudomonas, Mycobacterium,
      Moraxella, and Paracoccus, which were 91.3%, 90.8%, 84.2%, and 82.3%,
      respectively.

PMID- 12784611
TI  - Stimulatory effect of a dietary casein phosphopeptide preparation on the mucosal
      IgA response of mice to orally ingested lipopolysaccharide from Salmonella
      typhimurium.
AB  - The effect on immunoglobulin production of a commercially available casein
      phosphopeptide preparation (CPP-III) consisting mainly of bovine alpha s2-casein
      (1-32) and beta-casein (1-28) in mice that had orally ingested lipopolysaccharide
      (LPS) from Salmonella typhimurium was investigated. No significant difference in
      body weight gain was observed between the mice fed on the CPP-III-added diet and
      those fed on the control diet. The mice fed on the CPP-III-added diet exhibited
      similar serum and intestinal IgG, IgM, and IgE responses towards LPS to those fed
      on the control diet. In contrast, fecal and intestinal anti-LPS IgA and total IgA
      in mice fed on the CPP-III-added diet were significantly higher than in those fed
      on the control diet. Spleen cells from mice fed on the CPP-III-added diet
      produced larger amounts of IgA, IL-5, and IL-6 than cells from mice fed on the
      control diet. These results suggest that dietary casein phosphopeptide may
      protect a host from invasion of the intestinal mucosa by food-born pathogenic
      microorganisms.

PMID- 12784612
TI  - Dietary protein as a potent regulator of the hyaluronan synthase gene in rat
      skin.
AB  - The status of hyaluronan, the major glycosaminoglycan in the skin, is regulated
      by many factors such as cytokines and glucocorticoids. To examine whether and how
      protein malnutrition affects the status of skin hyaluronan, the hyaluronan
      content and mRNA levels of hyaluronan synthases (has) were analyzed in the skin
      of rats fed on a protein-free diet or on a 12% gluten diet. When these
      malnourishing diets had been given for 1 week, the hyaluronan content was
      significantly reduced as compared with that in rats fed on a 12% casein diet.
      Substantial falls in the mRNA levels of rhas2 and rhas3 were also observed. The
      reduction of mRNAs was already evident on the second day of treatment with the
      malnourishing diets. These results suggest that protein malnutrition has a
      primary impact on the gene expression of rhass, which leads to the reduction of
      hyaluronan content and to disfunction of the skin.

PMID- 12784613
TI  - Increased response of liver microsomal delta 6-desaturase activity to dietary
      methionine in rats.
AB  - The effects of dietary casein level (5-40%) on the liver microsomal phospholipid
      profile, delta 6-desaturase activity and related variables were investigated in
      rats to examine whether the dietary protein level affected the delta 6-desaturase
      activity through an alteration of the liver microsomal phospholipid profile. The
      effects of supplementing a 10% casein diet with certain amino acids were also
      investigated. The concentration of hepatic S-adenosylmethionine (SAM), the ratio
      of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) and the delta 6
      desaturase activity in liver microsomes, and the ratio of arachidonate to
      linoleate of microsomal PC increased with increasing dietary casein level. There
      were significant correlations between the dietary methionine content and hepatic
      SAM concentration, hepatic SAM concentration and microsomal PE concentration, and
      microsomal PE concentration and delta 6-desaturase activity. Supplementation of
      the 10% casein diet with methionine significantly increased the hepatic SAM
      concentration, PC/PE ratio, delta 6-desaturase activity, and
      arachidonate/linoleate ratio, whereas cystine supplementation had no or little
      effect on these variables. These increases induced by methionine were
      significantly suppressed by additional glycine. The results obtained here,
      together with those in our previous report, suggest that quantity and type of
      dietary protein might affect the delta 6-desaturase activity through an
      alteration of the liver microsomal profile of phospholipids, especially PE, and
      that the alteration of phospholipid profile might be mediated by a hepatic SAM
      concentration that reflects the dietary methionine level.

PMID- 12784614
TI  - Rapid measurement of phytate in raw soymilk by mid-infrared spectroscopy.
AB  - The phytate content in soymilk is known to affect tofu curdling. A rapid
      measurement of phytate from a water extract of soybean (raw soymilk) in an early
      stage of tofu processing was investigated using mid-infrared spectroscopy (IR)
      with an ATR accessory. IR absorption of phytate was observed from 1200 cm-1 to
      900 cm-1, and saccharide and protein in the extract also had IR absorption in the
      same region. In order to separate phytate from other components, the phytate was
      precipitated completely by the addition of calcium under alkaline condition (pH
      11.5). The precipitate was dissolved in citrate buffer (pH 6.0) and then used for
      IR measurement. The absorbance at 1070 cm-1 correlated well with the phytate
      content of the soymilk. The measurement of phytate in raw soymilk can be done
      rapidly by FT-IR measurement with an ATR accessory and gives reproducible values,
      which can be used for the measurement of phytate content in various soybeans for
      tofu making.

PMID- 12784615
TI  - Dietary fructooligosaccharides induce immunoregulation of intestinal IgA
      secretion by murine Peyer's patch cells.
AB  - Probiotic supplements induce immunological responses in the host, and dietary
      fructooligosaccharides (FOS) stimulate the growth of selected intestinal
      microflora. In this study we investigated the immunological influences of orally
      administrated FOS. BALB/c mice were orally administered 0-7.5% FOS for 6 weeks,
      and the intestinal mucosal immune responses were measured. In the 2.5%-FOS group,
      fecal IgA was significantly increased. IgA secretion by Peyer's patch (PP) cells
      was upregulated in a dose-dependent way in response to FOS and CD4+ T cells from
      PP showed a dose-dependent increase in production of interferon-gamma and
      interleukin (IL) 10, and a high response in production of IL-5 and IL-6. In
      contrast, FOS suppressed serum IgG1. Our findings suggest that FOS
      supplementation changes the intestinal environment of microflora, and leads to
      upregulation of IgA secretion in CD4+ PP cells in intestinal mucosa, and to
      suppression of the systemic immune response to type 2 helper T (Th2) dominant.

PMID- 12784616
TI  - Analysis of the pyruvate permease gene (JEN1) in glucose derepression yeast
      (Saccharomyces cerevisiae) Isolated from a 2-deoxyglucose-tolerant mutant, and
      its application to sake making.
AB  - We isolated mutants of S. cerevisiae in which expression of the JEN1 gene
      encoding a pyruvate transporter was insensitive to glucose repression. The
      isolated mutant GDR19 expressed JEN1 and absorbed pyruvate in the presence of
      glucose. In a DNA microarray analysis, GDR19 highly expressed many more genes,
      including JEN1, in the presence of glucose compared with the parental strain B29.
      Some of these genes are under the control of the transcription factor Mig1p and
      are normally repressed in the presence of glucose. The concentrations of organic
      acids in sake made with GDR19 were different from those in sake made with B29.
      Changes in the pyruvate concentration in the sake mash made with GDR19 were not
      very different from those in sake mash made with B29, and both GDR19 and B29
      expressed JEN1 during fermentation. When the ethanol concentration was over 2%,
      JEN1 expression in B29 was similar in the presence and absence of glucose. The
      expression of JEN1 in sake mash in spite of the presence of glucose appeared to
      be caused by the coexistence of ethanol.

PMID- 12784617
TI  - Purification, characterization, and gene cloning of lysyl aminoeptidase from
      Streptococcus thermophilus YRC001.
AB  - We purified and characterized an aminopeptidase from Streptococcus thermophilus
      YRC001 to obtain an enzyme for the application of reducing bitter-defect in
      cheese manufacturing. The purified enzyme was a monomer, and its molecular mass
      was estimated to be 90-100 kDa. It had a broad substrate specificity, and mostly
      hydrolyzed lysyl and leucyl peptides. The optimal temperature and pH for the
      enzyme were 35 degrees C and pH 6.5, respectively. EDTA, o-phenanthroline, and p
      chloromercuribenzoate inhibited its activity, therefore it was considered to be a
      metallopeptidase. The purified enzyme efficiently reduced the bitterness of a
      trypsin digest of reconstituted skim milk. Therefore, we cloned a gene for the
      enzyme from YRC001. The nucleotide sequence of a 2,940-bp XbaI fragment
      containing the gene was analyzed. The gene encoded 849 amino acids, and the
      calculated molecular mass for the mature enzyme (initial methionine is removed)
      was 96,434. The deduced amino acid sequence showed high homology with the known
      bacterial lysyl aminopeptidase (aminopeptidase N).

PMID- 12784618
TI  - Some properties of glycine aminotransferase purified from Rhodopseudomonas
      palustris No. 7 concerning extracellular porphyrin production.
AB  - Glycine aminotransferase (EC 2.6.1.4; GlyAT) was presumed to be an enzyme
      concerning the supply of glycine for the extracellular porphyrin production by
      Rhodopseudomonas palustris No. 7. GlyAT was purified from strain No. 7 as an
      electrophoretically homogenous protein. The enzyme was a monomer protein with the
      molecular weight of about 42,000. From the absorption spectrum of the enzyme (350
      nm, 410 nm), it was indicated that the enzyme had pyridoxal phosphate as a
      prosthetic group. The enzyme showed high substrate specificity for glutamate as
      an amino group donor. Apparent Kms for glutamate and glyoxylate were 6.20 mM and
      3.75 mM, respectively. The Vmax and Kcat for glutamate were 66.8 mumol/min/mg
      protein and 46.8 s-1, respectively. The Vmax and Kcat for glyoxylate were 68.8
      mumol/min/mg protein and 48.2 s-1. The optimum temperature and pH were 40-45
      degrees C and 7.0-7.5, respectively. The enzyme activity lowered to about 50% in
      the presence of 15 mM ammonium chloride.

PMID- 12784619
TI  - Decomposition of ethylene, a flower-senescence hormone, with electrolyzed anode
      water.
AB  - Electrolyzed anode water (EAW) markedly extended the vase life of cut carnation
      flowers. Therefore, a flower-senescence hormone involving ethylene decomposition
      by EAW with potassium chloride as an electrolyte was investigated. Ethylene was
      added externally to EAW, and the reaction between ethylen and the available
      chlorine in EAW was examined. EAW had a low pH value (2.5), a high concentration
      of dissolved oxygen, and extremely high redox potential (19.2 mg/l and 1323 mV,
      respectively) when available chlorine was at a concentration of about 620
      microns. The addition of ethylene to EAW led to ethylene decomposition, and an
      equimolar amount of ethylene chlorohydrine with available chlorine was produced.
      The ethylene chlorohydrine production was greatly affected by the pH value (pH
      2.5, 5.0 and 10.0 were tested), and was faster in an acidic solution. Ethylene
      chlorohydrine was not produced after ethylene had been added to EAW at pH 2.6
      when available chlorine was absent, but was produced after potassium hypochlorite
      had been added to such EAW. The effect of the pH value of EAW on the vase life of
      cut carnations was compatible with the decomposition rate of ethylene in EAW of
      the same pH value. These results suggest that the effect of EAW on the vase life
      of cut carnations was due to the decomposition of ethylene to ethylene
      chlorohydrine by chlorine from chlorine compounds.

PMID- 12784620
TI  - Effects of UV dose on formation of spontaneously developing pocks in Streptomyces
      azureus ATCC14921.
AB  - Spontaneously developing pocks (S pocks) of Streptomyces azureus ATCC14921 were
      formed by the both functions of conjugative plasmid pSA1 and lysogenic phage
      SAt2. The formation was affected by the dose of UV irradiation. The mean pock
      diameter in cultures treated with UV light at 0, 7.1, 14.2 and 21.3 x 10(2)
      microW. erg/cm, respectively, were 1.3, 0.4, 2.2, and 0.5 mm. The dose affected
      conjugative plasmid pSA1 related to pock formation. There was UV damage of
      autonomous pSA1 replicon and UV induction of the chromosomal integrated sequence.
      Increases and decreases in the amount of autonomous pSA1 replicon corresponded to
      increases and decreases, respectively, in the diameter of the pocks. Both pSA1
      and SAt2 syntheses were developed in the large pocks (1.3 and 2.2 mm), but only
      SAt2 synthesis was developed in the pinhole pocks (0.4 and 0.5 mm).

PMID- 12784621
TI  - Relationship between response to and production of the aerial mycelium-inducing
      substances pamamycin-607 and A-factor.
AB  - Respectively, exogenous pamamycin-607 and A-factor restored or stimulated aerial
      mycelium formation in 30 (67%) and 6 (13%) of 45 Streptomyces strains, and both
      restored or stimulated it in 5 strains (11%). Pamamycin-607 production was
      detected in 3 of those strains that responded to pamamycin-607. These findings
      indicate that pamamycin-607 acts on the common regulatory system for aerial
      mycelium formation in Streptomyces spp. but is not a universal autoregulator.
      Increased or decreased antibacterial production occurred in 5 strains in
      association with aerial mycelium formation by pamamycin-607 or A-factor.

PMID- 12784622
TI  - Microbial enantioselective reduction of acetylpyridine derivatives.
AB  - The microbial enantioselective reduction of acetylpyridine derivatives was
      studied. Many microorganisms were found to reduce 5-acetylfuro[2,3-c]pyridine
      (AFP) to (S)-5-(1-hydroxyethyl)furo[2,3-c]-pyridine (FPH). Candida maris IFO10003
      reduced AFP to (R)-FPH with high enantioselectivity. The microbial reduction
      reaction was optimized. The aeration conditions and glucose concentration
      affected the yield and stereoselectivity. The cells accumulated 17.5 g/l (107 mM)
      of (R)-FPH with a 99% yield and 97% enantiomeric excess (e.e.). A cell-free
      extract of C. maris accumulated 91.5 g/l (559 mM) with over 99% e.e. with
      enzymatic NADH regeneration. (R)-FPH is an important intermediate for the
      synthesis of HIV reverse-transcriptase inhibitor, and other optically active 1
      (pyridyl)ethanol derivatives are versatile chiral building blocks for asymmetric
      synthesis.

PMID- 12784623
TI  - Decreased tumorigenicity in vivo when transforming growth factor beta treatment
      causes cancer cell senescence.
AB  - We have previously reported that transforming growth factor beta (TGF-beta)
      triggers two independent senescence programs, 1) replicative senescence dependent
      upon telomere shortening and 2) premature senescence independent of telomere
      shortening, in the cell line of A549 human lung adenocarcinoma. In this study, we
      examined the possibility that cancer cell tumor phenotypes could be suppressed by
      forced senescence. We used A549 cells treated with TGF-beta for a long time (over
      50 days), where senescence was induced in a telomere-shortening-dependent or an
      independent way. Fully senescent A549 cells were elongated, acquired contact
      inhibition capabilities when reaching confluence, and secreted the senescence
      associated cytokine IL-6. Furthermore, senescent A549 cells had no tumorigenicity
      in nude mice. These results indicate that the forced induction of senescence in
      cancer cells may be a novel and potentially powerful method for advancing anti
      cancer therapy.

PMID- 12784624
TI  - Synthesis and characterization of hexadecadienyl compounds with a conjugated
      diene system, sex pheromone of the persimmon fruit moth and related compounds.
AB  - Hexadecadien-1-ol and the derivatives (acetate and aldehyde) with a conjugated
      diene system have recently been identified from a pheromone gland extract of the
      persimmon fruit moth (Stathmopoda masinissa), a pest insect of persimmon fruits
      distributed in East Asia. The alcohol and acetate showed their base peaks at m/z
      79 in a GC-MS analysis by electron impact ionization, but the aldehyde produced a
      unique base peak at m/z 84, suggesting a 4,6-diene structure. To confirm this
      inference, four geometrical isomers of each 4,6-hexadecadienyl compound were
      synthesized by two different routes in which one of two double bonds was
      furnished in a highly stereoselective manner. Separation of the two isomers
      synthesized together by each route was facilely accomplished by preparative HPLC.
      Their mass spectra coincided well with those of natural components, indicating
      that they were available for use as authentic standards for determining the
      configuration of the natural pheromone. Furthermore, other hexadecadienyl
      compounds, including the conjugated diene system between the 3- and 10-positions,
      were synthesized to accumulate the spectral data of pheromone candidates. 5,7
      Hexadecadienal interestingly showed the base peak at m/z 80; meanwhile, the base
      peaks of its alcohol and acetate were detected at m/z 79 like the corresponding
      4,6-dienes. The base peaks of all 6,8-, 7,9-, and 8,10-dienes universally
      appeared at m/z 67 like 9,11-, 10,12-, and 13,15-dienes, the spectra of which
      have already been published. Although 3,5-hexadecadienal was not prepared, base
      peaks at m/z 67 and 79 were recorded for the alcohol and acetate, respectively.

PMID- 12784625
TI  - Thermostabilization of ovalbumin by an alkaline treatment: examination for the
      possible implications of an altered serpin loop structure.
AB  - Ovalbumin, a member of the serpin superfamily, is transformed via an intermediate
      state into a non-cleaved, thermostabilized form (S-ovalbumin) during either the
      storage of unfertilized eggs or development of fertilized eggs; essentially the
      same thermostabilization also occurs upon in vitro incubation of isolated
      ovalubumin under alkaline conditions. To investigate the implications of a
      partial insertion of the alpha-helical serpin loop into beta-sheet A that has
      been proposed as a conformational mechanism for S-ovalbumin production, we
      examined the thermostabilization process of ovalbumin with different loop
      structures. When the thermostabilization processes were compared for the intact,
      P1-P1'-cleaved and P1-P1'/P8-P7-cleaved forms of egg white ovalbumin, both the
      rates for the conversion from the native to intermediate and from the
      intermediate to S-ovalbumin were almost indistinguishable among the three protein
      forms. Furthermore, the fully loop-inserted form of recombinant ovalbumin mutant
      R339T that had been thermostabilized by P1-P1' cleavage with Tm values from 72 to
      88 degrees C was further thermostabilized by an alkaline treatment, yielding a
      final product (loop inserted S-ovalbumin) with a Tm value of 93 degrees C. No
      significant difference was found between native ovalbumin and S-ovalbumin in
      respect of the rate of proteolytic cleavage of the loop by elastase and
      subtilisin. These data strongly suggest that S-ovalbumin is produced by a
      mechanism other than that of the partial loop insertion model.

PMID- 12784626
TI  - Synthesis of (+)-aptosimon, a 4-oxofurofuran lignan, by erythro selective aldol
      condensation and stereoconvergent cyclization as the key reactions.
AB  - The 4-oxofurofuran lignan, (+)-aptosimon (1), was synthesized from gamma
      butyrolactone (9). To construct the two benzylic chiral center of (+)-aptosimon
      (1), highly erythro selective aldol condensation and stereoconvergent SN1
      intramolecular cyclization were used as the key reactions.

PMID- 12784627
TI  - Family 19 chitinase of Streptomyces griseus HUT6037 increases plant resistance to
      the fungal disease.
AB  - Chitinase C (ChiC) is the first bacterial family 19 chitinase discovered in
      Streptomyces griseus HUT6037. In vitro, ChiC clearly inhibited hyphal extension
      of Trichoderma reesei but a rice family 19 chitinase did not. In order to
      investigate the effects of ChiC as an increaser of plant resistance to fungal
      diseases, the chiC gene was introduced into rice plants under the control of the
      increased CaMV 35S promoter and a signal sequence from the rice chitinase gene.
      Transgenic plants were morphologically normal. Resistance to leaf blast disease
      caused by Magnaporthe grisea was evaluated in R1 and R2 generations using a spray
      method. Ninety percent of transgenic rice plants expressing ChiC had higher
      resistance than non-transgenic plants. Disease resistance of sibling plants
      within the same line was correlated with the ChiC expression levels. ChiC
      produced in rice plants accumulated intercellularly and had the hydrolyzing
      activity against glycol chitin.

PMID- 12784628
TI  - Transepithelial transport of ferulic acid by monocarboxylic acid transporter in
      Caco-2 cell monolayers.
AB  - Our previous study (Biosci. Biotechnol. Biochem., 66, 2449-2457 (2002)),
      suggested that ferulic acid was transported via a monocarboxylic acid transporter
      (MCT). Transepithelial transport of ferulic acid was examined in this study by
      directly measuring the rate of its transport across Caco-2 cell monolayers.
      Ferulic acid transport was dependent on pH, and in a vectorical way in the apical
      basolateral direction. The permeation of ferulic acid was concentration-dependent
      and saturable; the Michaelis constant was 16.2 mM and the maximum velocity was
      220.4 nmol min-1 (mg protein)-1. Various substrates for MCTs, such as benzoic
      acid and acetic acid, strongly inhibited the permeation of ferulic acid,
      demonstrating that ferulic acid is obviously transported by MCT. Antioxidative
      phenolic acid compounds from dietary sources like ferulic acid would be
      recognized and transported by MCT by intestinal absorption.

PMID- 12784629
TI  - Production of an allelopathic polyacetylene in hairy root cultures of goldenrod
      (Solidago altissima L.).
AB  - Hairy roots of goldenrod (Solidago altissima L.) were induced by infecting axenic
      plants with Agrobacterium rhizogenes strain A4. Growth and allelopathic
      polyacetylene (cis-dehydromatricaria ester, cis-DME) production of two
      independent hairy root clones were examined in several culture media and light
      regimes. cis-DME contents in hairy roots were at the same level as those in
      normal roots. cis-DME production in root cultures was several-fold lower than
      that of native plants and greatly repressed by light.

PMID- 12784630
TI  - Contributions of polysaccharide and lipid regions of lipopolysaccharide to the
      recognition by spike G protein of bacteriophage phi X174.
AB  - A histidine-tagged G protein of bacteriophage phi X174 (HisG) bound strongly with
      lipopolysaccharide (LPS) of Escherichia coli C, one of a phi X174-sensitive Ra
      strain. The dissociation constant, Kd, was measured to be 0.16 +/- 0.04 microM by
      fluorometric titration. HisG showed slightly less affinity to LPSs of the
      insensitive Rc and Rd 2 strains having shorter R-core polysaccharide sequences
      than that of the sensitive Ra strains. The difference between the two types of
      LPS was demonstrated by CD spectra; LPSs of the sensitive strains increased the
      signal intensity for beta-sheet, while the insensitive strains decreased it. The
      chemically degraded LPS derivatives lacking a hydrophobic lipid region showed
      much less affinity to HisG, indicating the importance of the lipid region of LPS
      for strong binding with HisG. On the other hand, since the degraded derivatives
      increased the intensity of CD spectra, the polysaccharide region is thought to
      contribute to the conformation change of the protein.

PMID- 12784631
TI  - Hypoglycemic action of Cyclocarya paliurus (Batal.) Iljinskaja in normal and
      diabetic mice.
AB  - This study examined the hypoglycaemic activity of Cyclocarya paliurus (Batal.)
      Iljinskaja (C. paliurus) in ICR mice by oral glucose tolerance testing. The blood
      glucose level was significantly lower in the C. paliurus extract treatment group
      than in the control group after animals were given sucrose. This difference was
      not observed following the administration of glucose. We demonstrated that the
      chronological change in the level of blood glucose in genetically hyperglycemic
      obese KK-Ay mice is significantly lower when C. paliurus extract is administered
      daily for three weeks. An in vitro study showed that C. paliurus inhibits alpha
      glucosidase, a disaccharide-degrading enzyme in the small intestinal mucosa,
      leading to a decrease in the absorption of glucose into the blood and a
      subsequent lowering of the blood glucose level.

PMID- 12784632
TI  - Effects of anticoagulant from Spirodela polyrhiza in rats.
AB  - A fibrinolytic protease was purified from an Oriental medicinal herb, Spirodela
      polyrhiza (Choi, H. S., et al., Biosci. Biotechnol. Biochem., 65, 781-786
      (2001)). The protease hydrolyzed not only fibrin but also fibrinogen. The enzyme
      had an anticoagulant activity measured with activated partial thromboplastin
      time, thrombin time, and prothrombin time in rat plasma. It doubled all three at
      69, 29, and 221 nM, respectively. The protein had anticoagulant activity when
      given intravenously and orally. The maximum delay in the activated partial
      thromboplastin time was at the dose of 0.52 and 4.2 mg/kg for intravenous and
      oral administration, respectively. This protein may be useful in clinical
      applications for anticoagulation.

PMID- 12784633
TI  - Identification by HPLC-MS of carotenoids of the Thraustochytrium CHN-1 strain
      isolated from the Seto Inland Sea.
AB  - The orange-pigmented Thraustochytrium, CHN-1 strain was found to contain
      astaxanthin as the main carotenoid pigment. Echinenone, canthaxanthin,
      phoenicoxanthin and beta-carotene were also identified by high-performance liquid
      chromatography (HPLC) and HPLC-mass spectrometry. The total extractable
      carotenoid level was found to increase with culture age.

PMID- 12784634
TI  - Isolation and characterization of aromatics-degrading microorganisms from the gut
      of the lower termite Coptotermes formosanus.
AB  - We isolated aromatics-degrading bacteria from the gut of a lower termite,
      Coptotermes formosanus, using a mineral salt medium containing various aromatic
      compounds as the sole carbon source. Two species, Burkholderia sp. strain VE22
      and Citrobacter sp. strain VA53, were isolated by aerobic enrichment culture with
      veratraldehyde and vanillin, respectively. Strain VA53 could also grow and
      metabolize vanillin anaerobically.

PMID- 12784635
TI  - Dependence of the mechanical properties of a pullulan film on the preparation
      temperature.
AB  - The mechanical properties of pullulan films prepared at various temperatures were
      investigated. The films prepared at high temperatures (40 degrees C and 60
      degrees C; H-films) did not show any clear plastic deformation in tensile test,
      indicating that they were brittle. In contrast, those prepared at low
      temperatures (4 degrees C, 13 degrees C, and 25 degrees C; L-films) showed such
      deformation. The latter films had higher values for both tensile strength and
      elastic modulus than the former, indicating that the L-films were stiffer and
      more flexible than the H-films. Stretching the L-films clearly showed a shear
      deformation band inclined at 45 degrees to the stretching direction, indicating
      that they were amorphous.

PMID- 12784636
TI  - Heavy metal induction of Arabidopsis serine decarboxylase gene expression.
AB  - Serine (Ser) decarboxylase (SDC) catalyzes the conversion of Ser to ethanolamine
      (EA) in plants, while the physiological implications of the enzyme activity
      remain elusive. Here, we report that SDC gene expression in Arabidopsis was
      greatly induced by treatments with Ni2+ (24-fold) and Mn2+ (4-fold), and discuss
      possible genetic engineering strategies using the SDC gene for environmental
      stress management.

PMID- 12784637
TI  - Possible role of phytocassane, rice phytoalexin, in disease resistance of rice
      against the blast fungus Magnaporthe grisea.
AB  - In addition to momilactone, phytocassanes A through E (diterpene phytoalexins)
      were detected in rice leaves in fields suffering from rice blast. Furthermore,
      phytocassane accumulation was most abundant at the edges of necrotic lesions,
      indicating that the phytoalexins prevent subsequent spread of the fungus from the
      infected site. In pot experiments the pattern of phytocassane accumulation in
      rice leaves in an incompatible interaction (infection with an avirulent race of
      Magnaporthe grisea) was more rapidly induced than in a compatible interaction
      (infection with a virulent race of M. grisea).

PMID- 12784638
TI  - Antimutagenic activity of 8-hydroxyisoflavones and 6-hydroxydaidzein from soybean
      miso.
AB  - The antimutagenic activity of four isoflavones isolated from soybean miso toward
      three kinds of mutagens, AF-2, MNNG, and Trp-P-1, was evaluated by the Ames test.
      8-Hydroxyisoflavones had greater suppressive potency than that of daidzein, and 6
      hydroxydaidzein had almost the same activity as daidzein. These results indicated
      the number of hydroxy and methoxy groups and the position of these functional
      groups were important for antimutagenic activity.

PMID- 12784639
TI  - Antioxidative properties of Jaffa sweeties and grapefruit and their influence on
      lipid metabolism and plasma antioxidative potential in rats.
AB  - The effective substances (polyphenols, phenolic and ascorbic acids, flavonoids
      and dietary fibers) and antioxidative activities, using different radical
      scavenging tests, were determined for Jaffa sweeties and grapefruit. The
      antioxidative activities comprised the contributions from polyphenols, phenolic
      acids, flavonoids and ascorbate components, and were well-correlated with
      polyphenols and flavonoids. The correlation coefficient between the polyphenols
      and antioxidative activity varied from 0.73 to 0.99. All applied methods showed
      that sweeties had higher antioxidative activity than grapefruit. Experiments on
      laboratory animals show that diets supplemented with sweeties, and to a lesser
      extent with grapefruit, increased the plasma antioxidative potential and improved
      the lipid metabolism, especially in the rats fed with added cholesterol. These
      findings provide additional characterization of the nutritional value of citrus
      fruits and their influence on the lipid metabolism in rats.

PMID- 12784640
TI  - 9-Oxo-neoprocurcumenol from Curcuma aromatica (Zingiberaceae) as an attachment
      inhibitor against the blue mussel, Mytilus edulis galloprovincialis.
AB  - Neocurdione, isoprocurcumenol, and a new sesquiterpene, 9-oxo-neoprocurcumenol,
      were isolated from fresh rhizomes of Curcuma aromatica and Curcuma zedoaria
      (Zingiberaceae) as attachment inhibitors against the blue mussel, Mytilus edulis
      galloprovincialis. The structures of these compounds were elucidated on the basis
      of spectroscopic evidence.

PMID- 12784641
TI  - Expression in cereal plants of genes that inactivate Fusarium mycotoxins.
AB  - Trichothecene 3-O-acetyltransferase (encoded by Tri101) inactivates the virulence
      factor of the cereal pathogen Fusarium graminearum. Zearalenone hydrolase
      (encoded by zhd101) detoxifies the oestrogenic mycotoxin produced by the same
      pathogen. These genes were introduced into a model monocotyledon rice plant to
      evaluate their usefulness for decontamination of mycotoxins. The strong and
      constitutive rice Act1 promoter did not cause accumulation of TRI101 protein in
      transgenic rice plants. In contrast, the same promoter was suitable for
      transgenic production of ZHD101 protein; so far, five promising T0 plants have
      been generated. Low transgenic expression of Tri101 was suggested to be increased
      by addition of an omega enhancer sequence upstream of the start codon.

PMID- 12784642
TI  - Indispensability of the Escherichia coli carbonic anhydrases YadF and CynT in
      cell proliferation at a low CO2 partial pressure.
AB  - We found that a carbonic anhydrase, YadF, is essential for cell growth in the
      absence of another carbonic anhydrase, CynT, in Escherichia coli. However, mutant
      strains lacking both of them grew at high CO2 concentrations (5%), where non
      enzymatic mechanisms generate HCO3-. This suggests that these carbonic anhydrases
      are essential because they maintain HCO3- levels at ambient CO2 concentrations.

PMID- 12784643
TI  - Requirement of negative residues, Asp 95 and Asp 105, in S2 on membrane
      integration of a voltage-dependent K+ channel, KAT1.
AB  - Voltage-dependent K+ channels consist of a voltage-sensing region and a pore
      forming region. Here we have identified the negative residues of the second
      transmembrane segment in the plant voltage-dependent K+ channel, KAT1, which
      involves the function of voltage sensing. Point mutations at D95 and D105 but not
      D89 and D116 failed to complement the K+ uptake deficient properties of the
      mutant yeast. In vitro translation and translocation experiments showed that the
      membrane integration of the third and fourth segments involving voltage sensor
      were impaired by the replacement of D95 or D105 by serine. These data show that
      both the residues play a crucial role in the membrane topogenesis of the voltage
      sensor in KAT1.

PMID- 12784644
TI  - Salt stress induces the expression of Schizosaccharomyces pombe och1+, which
      encodes an initiation-specific alpha-1,6-mannosyltransferase for N-linked outer
      chain synthesis of cell wall mannoproteins.
AB  - The Schizosaccharomyces pombe Och1p is required for the initiation of outer chain
      elongation of N-linked oligosaccharides. In this report, we investigated the
      transcriptional control of the S. pombe och1+ gene and found that the expression
      of the och1+ gene was not regulated during the cell cycle, but was induced by
      NaCl and KCl through a transcription factor, Atf1p.

PMID- 12784645
TI  - Isolation and identification of the 3-hydroxy-5-hydroxymethyl-pyridinium compound
      as a novel advanced glycation end product on glyceraldehyde-related Maillard
      reaction.
AB  - Glyceraldehyde (200 mM) and N alpha-acetyllysine (100 mM) were incubated in 0.2 M
      sodium phosphate buffer (pH 7.4) at 37 degrees C for a week. A major compound,
      glyceraldehyde-related Maillard reaction product, was purified from the reaction
      mixture using reverse phase (ODS)-HPLC. It was identified as 1-(5-acetylamino-5
      carboxypentyl)-3-hydroxy-5-hydroxymethyl-pyridinium, named as GLAP
      (Glyceraldehyde derived Pyridinium compound), using NMR and MS analyses. It was
      suggested that GLAP as a novel advanced glycation end product (AGE) is one of the
      key compounds in the glyceraldehyde-related Maillard reaction.

PMID- 12784646
TI  - Microbial production of 2-deoxyribose 5-phosphate from acetaldehyde and
      triosephosphate for the synthesis of 2'-deoxyribonucleosides.
AB  - 2-Deoxyribose 5-phosphate was produced from acetaldehyde and dihydroxyacetone
      phosphate via D-glyceraldehyde 3-phosphate by Klebsiella pneumoniae B-4-4 through
      deoxyriboaldolase- and triosephosphate isomerase-catalyzing reactions. Under the
      optimum conditions, 98.7 mM 2-deoxyribose 5-phosphate was produced from 200 mM
      acetaldehyde and 117 mM dihydroxyacetone phosphate in 2 h with a molar yield of
      84%. The 2-deoxyriobse 5-phosphate produced was directly transformed to 2'
      deoxyribonucleoside by phosphopentomutase- and nucleoside phosphorylase
      catalyzing reactions.

PMID- 12784647
TI  - Formate-forming fungal catabolic pathway to supply electrons to nitrate
      respiration.
AB  - Pyruvate was catabolized anaerobically by resting cells of Fusarium oxysporum to
      form formate and acetate. Addition of nitrate decreased the accumulation of
      formate in the medium with concomitant formation of nitrite and N2O. The results
      suggested a unique metabolic pathway that occurs in fungi mediated by pyruvate
      formate lyase to supply electrons via formate to fungal denitrification.

PMID- 12784648
TI  - Characterization of beta-lactotensin, a bioactive peptide derived from bovine
      beta-lactoglobulin, as a neurotensin agonist.
AB  - beta-Lactotensin (beta-LT: His-Ile-Arg-Leu) is an ileum-contracting peptide
      derived from residues No. 146-149 of bovine beta-lactoglobulin. The ileum
      contracting activity of beta-LT was blocked by the NT1 antagonist SR48692. beta
      LT was selective for the neurotensin NT2 receptor while neurotensin was selective
      for the NT1 receptor. beta-LT is the first natural ligand showing selectivity for
      the NT2 receptor. beta-LT showed hypertensive activity after intravenous
      administration at a dose of 30 mg/kg in conscious rats, while neurotensin showed
      hypotensive activity. The hypertensive activity of beta-LT was blocked by
      levocabastine (1 mg/kg, i.v.), an NT2 antagonist. SR48692, which blocked the
      hypotensive activity of neurotensin, had no effect on the hypertensive activity
      of beta-LT. These results suggest that the hypertensive activity of beta-LT is
      mediated by the NT2 receptor. It was concluded that the NT1 and NT2 receptors
      mediate the opposite effect on blood pressure.

PMID- 12784649
TI  - [A novel system for the analysis of human hematopoietic stem cells using
      NOD/SCID/gamma c null mice].

PMID- 12784650
TI  - [Epstein-Barr virus infection of human natural killer-cell lines].

PMID- 12784651
TI  - [Significance and future directions of the pathological classification of
      malignant lymphoma].

PMID- 12784652
TI  - [Clinical significance of molecular cytogenetic prognostic factors in non-Hodgkin
      lymphoma].

PMID- 12784654
TI  - [Pathophysiology and treatment of acute myeloid leukemia].

PMID- 12784653
TI  - [Clinical significance of biological prognostic factors in non-Hodgkin lymphoma:
      analysis of serum and cell surface nm 23-H1 protein].

PMID- 12784655
TI  - [Safety and screening tests of blood transfusion].

PMID- 12784656
TI  - [CML with mu-BCR/ABL mRNA: clinical characteristics of our three cases and 26
      reported cases].

PMID- 12784657
TI  - [Late appearance of Philadelphia chromosome with the p190 BCR/ABL chimeric
      transcript in acute myelogenous leukemia progressing from myelodysplastic
      syndrome].
AB  - We report a late appearance of the Philadelphia chromosome (Ph) with the p190
      BCR/ABL chimeric transcript in a 69-year-old patient with acute myelogenous
      leukemia (AML) that had evolved from myelodysplastic syndrome (MDS). In July
      1997, the patient was found to have pancytopenia caused by refractory anemia with
      excess of blasts, which evolved into AML in 4 months. The leukemic cells were
      positive for CD13, CD14, CD33, and HLA-DR and had a normal karyotype. The patient
      achieved a complete remission after combination chemotherapy. However, his
      leukemia relapsed in November 1999, with the appearance of leukemic cells
      positive for CD7, CD13, CD34, and HLA-DR with a 46, XY, add (18) (p11) karyotype.
      The patient failed to achieve the second remission after several courses of
      intensive chemotherapy. When the number of blastic cells, showing the same
      surface phenotypes, in the peripheral blood increased drastically in April 2000,
      chromosomal analysis of leukemic cells revealed a 46, XY, t(9;22) (q34;q11),
      add(18)(p11) karyotype. The fusion of the BCR and ABL genes was confirmed by
      fluorescence in situ hybridization analysis, and the reverse transcription
      polymerase chain reaction analysis further revealed the presence of the p190
      BCR/ABL chimeric transcript. The appearance of the Ph chromosome in the course of
      MDS transforming to AML is very rare and may be correlated to the disease
      progression.

PMID- 12784658
TI  - [Successful treatment of splenic lymphoma with villous lymphocytes by rituximab
      and laparoscopic splenectomy].
AB  - We report on a case of splenic lymphoma with villous lymphocytes (SLVL) which
      responded well to rituximab. A 50-year-old man was admitted because of
      splenomegaly. Abnormal lymphocytes of B cell lineage with moderately basophilic
      cytoplasm and unevenly distributed villi (villous cells) were found, both in the
      peripheral blood and bone marrow. CHOP and CHOP-E were performed, without any
      remarkable change in the size of the spleen. However, after infusion of rituximab
      (375 mg/m2, once weekly for 2 weeks), there was a marked reduction of the spleen
      size and the number of circulating villous cells. Splenectomy was performed
      afterwards, followed by 2 cycles of rituximab infusion. The patient is now
      followed on an outpatient basis without any sign of relapse.

PMID- 12784659
TI  - [Successful treatment with imatinib mesylate for Philadelphia chromosome-positive
      refractory acute myeloid leukemia].
AB  - A 51-year-old man was diagnosed as having Philadelpha (Ph) chromosome-positive
      acute myeloid leukemia (AML) with major-BCR/ABL mRNA. He achieved complete
      remission after induction chemotherapy. Five months later, he was again positive
      for the Ph chromosome despite additional chemotherapy. He was therefore treated
      with imatinib mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, at a
      dose of 600 mg/day. However, the treatment was interrupted because of
      thrombocytopenia, skin eruption and face edema. After the patient recovered from
      these side effects, imatinib was readministered at a dose of 400 mg/day and a
      complete cytogenetic response was achieved. Imatinib is expected to be an
      effective drug for Ph chromosome-positive AML.

PMID- 12784660
TI  - International policies on alcohol impaired driving: are legal blood alcohol
      concentration (BAC) limits in motorized countries compatible with the scientific
      evidence?
AB  - Borkenstein et al. (1974) study indicated that drivers with BACs of 0.05 to 0.09
      per cent were twice as likely to crash as drivers with a zero BAC. Drivers with
      BACs from 0.10 to 0.14 per cent were ten times as likely to have a fatal crash in
      1964. There have been numerous efforts during the history of motorized countries
      to control the consumption of alcohol and the problems associated with it through
      legislative mandate, it was not until the 1970s that acceptance of legal BAC
      (Blood Alcohol Concentration) limits laws became widespread. In particular, as
      more and more people drive automobiles, the number of traffic accidents involving
      drunken drivers has soared, and many of these are known to be related to the
      consumption of alcohol. Thus, legislators find themselves under increasing
      pressure to find a reasonable and fair solution to the question of alcohol
      impaired driving, as the scientific evidence about alcohol consumption level and
      psycho motor functions impairment came to clear. A landmark event in the
      development of policies regarding impaired driving was the establishment of the
      fact that consumption of alcohol does, in fact, increase the probability of
      traffic crashes. Legal limit laws specify a maximum permissible BAC limit for
      drivers. Currently, a BAC laws range from zero tolerance and 0.02 to 0.10%
      constitutes prima facie evidence in most countries for 'Driving under Influence
      of Alcohol.' This latter standard is too permissive, as driving skills
      deteriorate and crash involvement risk increases beginning at 0.02%. There are
      consequences attached to setting a BAC limit so high that a 72 kg man can drink
      five bottles of beer and still be under legal limit. In this sense high legal BAC
      limit may influence people to make bad estimates of their relative risk of injury
      or death while driving. Provided there is adequate political will, millions of
      lives could be saved in the coming years. This review is an attempt to examine in
      detail the available information about legal BAC limit laws, and issue of
      considerable interest to both policy makers and the public.

PMID- 12784661
TI  - [Changes of serotonergic neurons induced by low dose nicotine in rat forebrain].
AB  - Nicotine has been reported to exert several biological and pharmacological
      activities in central nervous system. There are many studies on the relationship
      between dopaminergic neurons and nicotine dependence. However, the relevance
      between nicotine and serotonergic neurons on dependence remains unknown. We
      demonstrate here that the effect of continuous low dose nicotine administration
      on setoronergic neurons (5-HT) immunoreactive fibers and terminals were increased
      in nicotine (0.5 mg/kg/day, 28 days) treated rat forebrain including anterior
      cingulate cortex and hippocampus. These results indicate that low dose nicotine,
      levels of smoking, may be related the developing the dependence of nicotine via
      the changes of 5-HT neurons in forebrain.

PMID- 12784662
TI  - [Decade of the activity of AC in Kochi].

PMID- 12784663
TI  - ["Time, place and person" and neurology].
AB  - The Department of Neurology, Hokkaido University, has been established since
      1987, however the bases for neurology had been cultivated through psychiatry and
      neurosurgery in Hokkaido, especially under the pioneering work by Professor
      Mitsuo Tsuru. Hokkaido, the northernmost island of Japan, is located between 42
      and 46 degrees, and the people have ancestors from various parts of Japan, since
      this island was reclaimed about 130 years ago. Three major neurological
      disorders, such as multiple sclerosis(MS), spinocerebellar degeneration(SCD) and
      Parkinson disease (PD), were discussed on the bases of Hokkaido island. We proved
      the existence of definite north-south gradient of MS, prevalence rate of 8.6 in
      Tokachi, Hokkaido, compared with 1-2 in the southern island. SCD, especially
      hereditary SCD, such as SCA1, SCA2 and SCA14 were reported from Hokkaido. The
      epidemiological studies of PD showed the prevalence rate of 104.6 at Iwamizawa,
      Hokkaido in 2000, and we proposed the prevalence rate of PD was close to those of
      Western countries under the collaborative works with Yonago, Kyoto, and Kagoshima
      by 2001. Neurology, and its specialization and training programs were also
      discussed to propose the importance of Neurology in Japan.

PMID- 12784664
TI  - [A historical note on the research for amyotrophic lateral sclerosis in Japan].

PMID- 12784665
TI  - [The growing-up and background of clinical neurology in Japan].
AB  - Japan strictly closed the country to foreigners except for the Dutch and Chinese
      in the days of Tokugawa Regime for about 200 years (1639-1858). During this
      period, Japanese neurology made a start. In 1774, five Dutch scholars in Edo
      (Tokyo at present) translated the Dutch version of a German textbook "Anatomische
      Tabellen". After the Meiji Restoration, Japan was rapidly westernized. The modern
      neurology was introduced mainly from Germany, France and the United Kingdom into
      Japan, and exerted a fruitful influence on the subsequent Japanese neurology.
      Prof. Hiroshi KAWAHARA published the first textbook of neurology (in Japanese) in
      1897. Prof. Kinnosuke MIURA founded the first neurological journal in Japan in
      1902. These two pioneers in Japanese neurology had their medical education under
      Prof. Erwin Baelz at the University of Tokyo during the last-eighteenth century.

PMID- 12784666
TI  - [A challenge for revealing common molecular mechanisms underlying
      neurodegenerative disorders].
AB  - Many neuodegenerative disorders manifest disease-specific phenotypes, and thus it
      was thought impossible to deduce a common molecular mechanism underlying many, if
      not all, neurodegenerative disorders. However, protein aggregates and vacuoles
      are almost universally found in degenerating neurons, suggesting the existence of
      similar molecular processes in neuronal cell death. In 1994, we identified the
      gene responsible for Machado-Joseph disease (MJD). Not only MJD but also another
      8 inherited neurodegenerative diseases, including Huntington's disease are caused
      by the expansion of CAG repeats encoding polyglutamines. Indeed, we have shown
      that polyglutamines have the ability to self-aggregate and induce
      neurodegeneration and neuronal cell death, leading to a proposal of
      'polyglutamine disease'. Furthermore, we have identified ter94/VCP, a member of
      the AAAAT-Pase, as a key molecule in neurodegeneration. VCP co-localizes not only
      with polyglutamine aggregates but also other protein aggregates and Lewy bodies.
      Moreover, profound deficits in its ATPase activity are found to severely affect
      ER quality control, leading to abnormal ER expansion and cell death. These lines
      of evidence indicate that VCP functions not only as a common sensor for abnormal
      protein accumulations but also as a mediator of neurodegenerative phenotypes;
      excessive accumulation of abnormal proteins may inactivate VCP's ATPase in
      several neurodegenerative disorders, eventually leading to the
      neurodegenerations. A proper regulation of VCP function is thus proposed to lead
      to novel treatments that are effective in a broad spectrum of neurodegenerative
      diseases.

PMID- 12784667
TI  - [Risk factors for cerebral infarction: current topics and new developments].
AB  - Current topics and new developments in risk factors for ischemic stroke were
      reviewed. Hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation,
      cigarrette smoking, and heavy alcohol drinking have been established as being
      common treatable risk factors for stroke. Recent studies have clarified that
      homocysteine, various cardiac sources of embolism such as patent foramen ovale,
      antiphopholipid antibodies, lipoprotein (Lp) abnormalities including Lp(a) and
      remnant-like particle, insulin resistance or hyperinsulinemia, infectious
      diseases such as Chlamydia Pneumoniae, and CRP are additional risk factors for
      stroke. In addition, genetic studies using single nucleotide polymorphisms have
      suggested that many gene polymorphisms are significant risk factors for certain
      subpopulations of stroke, which is recognized to be a polygenic disease.
      Management of these risk factors is crucial for primary prevention of stroke,
      which is the leading cause of death or disability all over the developed
      countries.

PMID- 12784668
TI  - [Differential diagnosis of spinocerebellar ataxia].
AB  - Spinocerebellar ataxia (SCA) is a group of heterogeneous disorders. In Japan,
      approximately 60% of SCA consist of sporadic disorders, and the rest mostly
      consists of a variety of late-onset dominant disorders. In the latter, MJD, SCA6,
      DRPLA, SCA1 and SCA2 are frequent in this order, and others are rare. All these
      disorders are caused by unstable expansion of CAG repeat in the coding region of
      each responsible gene. Among those disorders, SCA6 manifests late-onset pure
      cerebellar ataxia and frequently associated with positioning vertigo. In other
      disorders, phenotype variation, clinical severity, and onset of age are known to
      correlate inversely with the CAG repeat size. Such variation even in a given
      disorder is often difficult to apply single criteria to diagnose the disorder
      based on its clinical findings alone. MSA is a major disorder of sporadic SCA.
      Signs of cerebellar ataxia, parkinsonism, autonomic disturbance are incorporated
      into current diagnostic criteria. However, cases meeting the criteria of
      autonomic disturbances are confined to the advanced stage of the illness or rare
      cases starting with obvious dysautonomia. These problems indicate that the
      criteria need further adjustment.

PMID- 12784669
TI  - [Amyotrophic lateral sclerosis-parkinsonism-dementia complex of the Kii Peninsula
      of Japan].
AB  - The Hohara village of the Kii peninsula is one of the high incidence ALS foci,
      and the high incidence was reported to have ended in early 1980s. However, we
      have found the ALS incidence rate has been still high, more than 100 times of the
      other areas of Japan. In addition, we have found many cases of parkinsonism
      dementia complex (PDC). ALS and PDC often occur simultaneously in a single
      patient or in a single family. Family history was positive in more than 70% of
      patients. ALS and PDC showed common neuropathological findings consisting of ALS
      pathology and many neurofibrillary tangles (NFT) without senile plagues, and
      isoform pattern of NFT tau protein was similar to that of Alzheimer disease (AD),
      but different from that of progressive supranuclear palsy (PSP) or Pick's disease
      (PiD). Kii ALS/PDC may be a novel tauopathy that differ from AD, PSP or PiD.

PMID- 12784670
TI  - [Parkin gene: its mutations and function].
AB  - To date, nine forms of familial Parkinson's disease (PD) have been mapped to
      different chromosome loci. Among them, Park 2, which is an autosomal recessive
      form (AR-JP) by parkin gene mutations, is the most common form of familial PD.
      Indeed, this form of familial PD distributed in the world wide such as European,
      North American, Turkish, Japanese families. Moreover, we know that the role of
      parkin protein in the brains is to break down misfolded proteins as an ubiquitin
      protein ligase. Very recently, although the presence of Lewy bodies have been
      reported in one case, the lack of Lewy bodies in parkin-mutated brains suggests
      us a fundamental pathology for Lewy bodies. Therefore, the parkin function could
      be essential for the Lewy body formation. Thus, the elucidation of the exact role
      of parkin protein provides us the mechanisms of the formation of Lewy bodies in
      common forms of sporadic PD. Therefore, it is important to detect the substrates
      for the parkin protein. Recently, several candidate substrates have been reported
      including CDCrel-1, synphilin-1, alpha-synuclein-22 (o-glycosylated alpha
      synuclein), and Peal-receptor. The question is accumulation of which substrates
      are responsible for the nigral neuronal death in Park 2 linked brain.

PMID- 12784671
TI  - [Neurology of praxis disorder].
AB  - Based on the analysis of four types of basic praxis disorders, i.e. disturbance
      of single tool use (ideational apraxia), impairment of pantomiming ability to use
      a tool (ideomotor apraxia), inability to copy a non-meaningful finger pattern
      (limbkinetic apraxia), and inability to reproduce a series of hand movements
      (dynamic apraxia), a hypothesis on the neural organization of higher order motor
      production was proposed. It was stressed that these four types of praxis disorder
      should not be considered as different kinds of movement disorders at the same
      level. Rather they are examples of the motor realization disorder each
      representing a different level of neural substrate in a hierarchically organized
      motor structure.

PMID- 12784672
TI  - [Pathology of neurodegenerative diseases: with special reference to Parkinson's
      disease and amyotrophic lateral sclerosis].
AB  - The causes of Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)
      are still unknown. Aging, environmental factors and genetic factors may be
      involved in the development of these illnesses, especially the sporadic
      phenotypes. The details of PD pathology have made remarkable advances in the last
      5 years, after the discovery of mutation of the alpha-synuclein gene in families
      with PD: all of the Lewy bodies (Lewy filaments) in familial and sporadic PD
      contain the gene product alpha-synuclein. Further studies are necessary to
      elucidate the mechanisms underlying the development of PD, and to determine the
      therapeutic targets through which it may be possible to prevent the disease. With
      regard to the pathology of ALS, it is of great importance that in this disease,
      characteristic neuronal cytoplasmic inclusions (i.e., Bunina bodies and
      ubiquitinated inclusions) have been described in the lower motor neurons. At
      present, however, compared with the Lewy bodies in PD, much less is known about
      the profiles of the inclusions associated with ALS. Early identifications of the
      proteins that constitute these inclusions would be desirable if we are to
      elucidate the molecular pathology, and thus the mechanisms underlying ALS.

PMID- 12784673
TI  - [Diagnostic imaging of the CNS disorders].
AB  - In this lecture, I attempted to demonstrate MR imaging of the cerebral tracts,
      medullospinal junction and spinal cord. Cortical migration disorders includes
      heterotopic gray matter, pachygyria and polymicrogyria. Delayed myelination and
      dysmyelination are shown as hyper signal intensity in the white matter on T2
      weighted images. Edema and demyelination impair the tracts, and they are
      precisely evaluated by T2-weighted, FLAIR and diffusion-weighted MR images.
      Reversible posterior leukoencepalopaty syndrome is caused by vasogenic edema of
      the subcortical association fibers and by cytotoxic edema of the cortical gray
      matter, due to hypertension, renal dysfunction, drugs and so on. Antiepileptic
      drug toxicity may cause reversible edema of the splenium. Secondary demyelination
      includes Wallerian degeneration and transneuronal degeneration. Hypertrophic
      olivery degeneration is transneuronal degeneration associated with disruption of
      Guillain-Mollaret's triangle, and it is shown as high signal intensity of the
      inferior olivery nucleus on T2 and FLAIR images. Limbic system and Papez's
      circuit play an important role in epilepsy associated with mesial temporal
      sclerosis. Transneuronal degeneration through the Papez's circuit can be
      appreciated by the findings of atrophy of the fornix and mammillary body.

PMID- 12784674
TI  - [Dystroglycan linkage and muscular dystrophy].
AB  - Dystroglycan is a key complex between basal lamina laminin, extracellularly and
      membrano-cytoskeleton, intracellularly. The damage of this linkage is turned out
      to cause muscular dystrophies. Dystroglycan knockout is lethal. Dystroglycan
      associated intracellular proteins such as dystrophin, dystrobrevin, sarcoglycans,
      plectin and caveolin-3 are responsible for causing severe (Duchenne type) and
      moderate forms (Becker, LGMDs). Laminin, dystroglycan-binding extracellular
      protein, is deficient in the most severe form of congenital muscular dystrophy
      with normal intelligence and eye. Recently, a remarkable progress is made in most
      severe forms of congenital muscular dystrophy with anomalies of brain and eye
      such as Fukuyama type (Japan) and muscle-eye-brain disease (Finland). The gene
      product for Fukuyama type, fukutin, belongs to a family of glycosylation enzymes
      in bacteria and yeast. Since alpha-dystroglycan contains 14-15 o-glycans, ser/thr
      mannose 2-1 GlcNAc 4-1 Gal 3-2 Sial in the middle third mucin-domain and the sial
      o-glycan is essential for laminin-binding, and since alpha-dystroglycan is
      defective in Fukuyama type sarcolemma with anti both sugar moiety- and peptide
      antidodies, defective fukutin causes incomplete o-glycosylation of alpha
      dystroglycan. In '02, it is clarified that a glycosylation enzyme, POMGnT1 which
      modifies GlcNAc onto ser/thr-mannose, is defective in 6 MEB patients. The loss of
      the enzyme activity is turned out to lose alpha-dystroglycan from sarcolemma of
      MEB. These data strongly suggests that o-glycosylation defect of alpha
      dystroglycan causes the most severe congenital muscular dystrophy such as
      Fukuyama type, MEB and Walker Warburg syndrome.

PMID- 12784675
TI  - [Clinical neurophysiology of movement disorders].
AB  - Movement disorders are physiologically studied based on three principles; 1.
      relation between movements and brain activities, 2. excitability and inhibitory
      mechanisms of motor cortices, and 3. sensorimotor integration. Regardless of
      voluntary or involuntary movements, the study on how the movement in question is
      related to brain activities provides an important information as to its
      pathophysiology. This can be studied by jerk-locked averaging of
      electroencephalogram or magnetoencephalogram in case of involuntary movements and
      movement-related cortical potentials for voluntary movements, change of cortical
      rhythmic activities in relation to movement (event-related desynchronization or
      synchronization), cortico-muscular coupling(coherence), and neuroimaging
      techniques such as PET, SPECT and fMRI. Excitability and inhibitory mechanisms of
      motor cortices can be studied by applying transcranial magnetic stimulation.
      Positive and negative myoclonus of cortical origin is related to abnormal
      hyperexcitability of the positive and negative components, respectively, of the
      primary motor cortex (M1). Focal dystonia is associated with impairment of
      inhibitory mechanisms in M1. The simplest form of abnormal sensorimotor
      integration is cortical reflex myoclonus. In the choice reaction time task,
      contingent negative variation is reduced in a task-specific way in focal
      dystonia. Effect of movement on somatosensory processing (gating) is abnormal
      immediately before the movement onset in focal dystonia, again in a task-specific
      way. Daily activities like gait can be studied by SPECT which does not require
      fixation of the subject's head during the task performance.

PMID- 12784676
TI  - [Radiological evaluation of non-neoplastic intramedullary lesions of the spinal
      cord].
AB  - Radiological evaluation of the non-neoplastic intramedullary lesions of the
      spinal cord includes lesion detection and characterization in order to make
      definitive diagnosis or to narrow differential diagnoses. Radiologist may be able
      to guide clinicians as to next diagnostic step when definitive diagnosis cannot
      be made. Treatment effect can be also assessed. Among other radiological
      modalities, MRI plays the most important role in the evaluation of the spinal
      lesions, particularly of the intramedullary lesions. MRI findings of
      intramedullary lesions can be divided into morphological and signal
      abnormalities. Morphological abnormalities include presence of an abnormal
      structure, deviation or deformity of normal structures, and enlargement or
      atrophy of the spinal cord. Signal abnormalities include T2 prolongation (often
      associated with T1 prolongation), T1 and T2 shortening, and abnormal contrast
      enhancement. There may be only one finding, or multiple findings may be present
      in combination. Signal changes and abnormal contrast enhancement with or without
      cord enlargement are the most common but important findings. There are a few
      disease entities with pathognomonic MRI findings, but it is often difficult to
      make definitive diagnosis based on MRI findings alone. It is imperative not only
      to have thorough knowledge of imaging findings various diseases, but also to
      pursuit radiological evaluation correlating with clinical and laboratory
      findings.

PMID- 12784677
TI  - [Medical approach to intraparenchymal spinal cord disorders].
AB  - Diagnosis depends on the clinical manifestations, blood or cerebrospinal fluid
      study and MRI findings. Acute and subacute intraparenchymal spinal cord disorders
      are due to vascular disorders or myelitis. Spinal cord infarction is associated
      with dissecting aortic aneurysm, surgical clipping of aortic aneurysms, aortic
      atherosclerosis or hypotension from any cause. Hematomyelia results from trauma,
      vascular malformations, vasculitis, or a coagulation disorder. Acute infectious
      myelopathies result from direct invasion of the spinal cord by bacteria,
      parasite, or virus. The cause of acute or subacute inflammatory disease include
      multiple sclerosis, Devic disease, acute disseminated encephalomyelitis, SLE, or
      sarciodosis. Sarcoidosis sometimes requires differential diagnosis with cord
      tumor. Chronic intraparenchymal spinal cord disorders are due to syringomyelia,
      familial spastic paraplegia, HTLV-1 associated myelopathy, adrenomyeloneuropathy,
      and vascular malformations. HTLV-1 associated myelopathy present with progressive
      spastic paraplegia with bladder disturbance and has antibodies to HTLV-1 in the
      cerebrospinal fluid and serum. Diagnosis of adrenomyeloneuropathy is made by
      demonstration of elevated levels of very long chain fatty acids in plasma.
      Vascular malformations are important lesions because they present a treatable
      cause of progressive myelopathy.

PMID- 12784678
TI  - [Surgical approach for non-neoplastic intramedullary lesions].
AB  - There are many non-neoplastic intramedullary lesions that mimic intramedullary
      neoplasm. They are consisted of demyelination, granulomatous disease, infections,
      radiation myelopathy, vascular lesions, and syringomyelia. In this report, the
      authors described its differential diagnosis in clinical and neuroradiological
      findings. Furthermore, we mentioned its surgical approach for several non
      neoplastic lesions. Syringomyelia and spinal AV fistula are both good candidate
      of surgical treatments. We would like to stress that good cooperation between
      neurologist, neuroradiologist, and neurosurgeon is important to differentiate non
      neoplastic lesions and surgical biopsy is final procedure to confirm their
      pathology.

PMID- 12784679
TI  - [Genetic diagnosis in neurology--an overview].
AB  - The genetic diagnosis is now most popular in Neurology in these 20 years. The
      localization of Huntington's disease gene was first determined in 1983 through a
      procedure of the genetic linkage using DNA markers. The identification of the HD
      gene was achieved 10 years later. Since a simple PCR technique made it possible
      not only to fix the accurate diagnose of the disease but also to achieve the
      presymptomatic diagnosis of HD, we should prepare for the coming requests of
      genetic testing by at risk persons. We persuade such persons not to receive the
      test, simply because we can't not only to prevent the disease but also to cure
      the disease at the moment. However, we can't help testing for persons who fulfill
      the following conditions; 1) adult persons who are at risk of the molecular
      genetically verified hereditary disease, 2) persons who know the disease itself
      and its genetics exactly, 3) persons whose requests for the presymptomatic
      testing is absolutely spontaneous, not being forced by the third party, such as
      an insurance company or a parent of fiance, 4) persons who will be
      psychologically and financially supported by friends or relatives when the result
      of the test was positive. In the Symposium, I will present some problems in the
      genetic testing particularly from the ethical point of view.

PMID- 12784680
TI  - [Multidisciplinary approach to genetic testing for hereditary neuromuscular
      diseases].
AB  - The benefit of genetic testing for hereditary neuromuscular diseases is accurate
      and rapid diagnosis. On the other hand, it raises several ethical, legal, and
      psychosocial issues because the test results may greatly influence the life plan
      or life style of the applicant. In particular, in case of predictive or prenatal
      genetic testing, or carrier detection for family relatives, careful genetic
      counseling and psychosocial support are needed for applicants. When requests for
      predictive or prenatal genetic testing, or carrier detection for healthy
      relatives are received, a multidisciplinary approach should be taken. A team that
      consists of a geneticist, neurologist, psychiatrist, psychologist, genetic nurse,
      and social worker should carefully conduct genetic counseling sessions. It is
      quite important to build effective communication and coordination of activities
      among the applicant, the applicant's family and members of the counseling team
      during pre-test counseling sessions. This will help applicants feel satisfied
      with their own decision as to whether they will receive genetic testing or not.
      Furthermore, it will help applicants cope with an unfavorable test result.

PMID- 12784682
TI  - [Neuropathology of malignant lymphoma and its related disorders].
AB  - Primary central nervous system lymphoma are characterized by macroscopically the
      tumor mass formation in the cerebral hemisphere including basal ganglia and
      corpus callosum and diffuse invasion particularly in the periventricular region,
      and microscopically lymphoma cells proliferation around the vessels and diffuse
      invasion into the brain parenchyma. Secondary involvement of central nervous
      system by systemic lymphoma are characterized by tumor cells invasion to the
      meninges and cranial and spinal nerve roots and tumor cells invade to the brain
      parenchyma along the perivascular space. Tumor nodule formation are very rare and
      tumor cells are not found in the lumen of the vessels. In the cases of extradural
      metastasis of systemic lymphoma, in addition to spinal cord compression,
      secondary circulatory disturbance, particularly venous congestion are also
      important factor for the spinal cord damages. In intravascular malignant
      lymphoma, not only tumor cells proliferation in the lumen of small sized vessels,
      but also secondary vasculitis and fresh and old thrombus formation are important
      for the development of multiple infarction of central nervous system. And spinal
      cords particularly in the levels of lumbosacral spinal cord are dominantly
      involved. Recently, according to the longness of clinical course of intravascular
      malignant lymphomatosis, cases with tumor mass are reported and these tumor mass
      are very similar to that of primary central nervous system lymphoma.

PMID- 12784681
TI  - [Clinical aspects and pathogenesis of neurological complications due to malignant
      lymphomas].
AB  - Malignant lymphomas cause various neurological complications by several ways.
      They include 1) infiltration and compression due to lymphoma itself, 2) ischemia
      due to intravascular proliferation of lymphoma cells, 3) paraneoplastic syndrome,
      4) immunodeficiency due to lymphomas, 5) organ dysfunction due to lymphomatous
      infiltration, and 6) complication related to therapies against lymphomas. We
      presented 4 patients with neurological complications caused by B cell lymphomas
      as follows. Our first patient was a 67-year-old woman with primary intracranial
      lymphoma whose onset simulated that of a cerebral infarct. The second patient was
      a 52-year-old man with lymphoma, who developed myelopathy caused by an intradural
      extramedullary spinal cord tumor. He received chemotherapy and radiation therapy,
      followed by complete remission. The third was a 80-year-old man with left
      cavernous sinus syndrome, which did not respond to therapies against lymphoma.
      The fourth was a 55-year-old man who presented with numb chin syndrome on both
      sides, followed by multifocal lymphomatous involvement of the cranial nerves,
      spinal roots and leptomeninges. Malignant lymphomas may affect any regions of the
      central and peripheral nervous systems by various ways. Early diagnosis and
      treatment are essential for the better outcome of neurological complications due
      to lymphomas.

PMID- 12784683
TI  - [Molecular genetic analysis of malignant lymphoma].
AB  - A semi-nested polymerase chain reaction for the variable region of the
      immunoglobulin heavy and light chain genes (VH, V kappa and V lambda) was used to
      investigate the cell of origin and the clonal history in intravascular malignant
      lymphomatosis (IML), primary central nervous system lymphoma (PCNSL) and diffuse
      large B-cell lymphoma (DLBCL). A monoclonal band of VH and V kappa genes was
      detected in all cases of IML. A monoclonal band of VH was also detected in PCNSL
      and DLBCL. The nucleotide sequences of the VH and V kappa genes were determined.
      Numerous point mutations were present in all of the VH and V kappa genes. Ongoing
      mutation was observed in 3 of 5 IML cases, in 1 of 5 PCNSL and in 4 of 12 DLBCL.
      Because the process of immunoglobulin gene hypermutation is thought to occur at
      the germinal center (GC) stage of B cell development, these results suggest that
      IML, PCNSL and DLBCL are derived from GC B cells or their descendants. Using this
      reliable and sensitive method, a monoclonal band was detected in peripheral blood
      samples from 5 IML cases. The diagnosis of IML was confirmed by biopsies or
      autopsies in 4 cases. The sequences obtained from biopsied tissues and blood
      samples were found to be identical in each case in 3 cases examined.

PMID- 12784684
TI  - [Central nervous system lymphomatoid granulomatosis].
AB  - Lymphomatoid granulomatosis (LYG) is a rare multiple organs disease with
      characteristic angiocentric lymphoproliferative features, most frequently
      involving the lung, skin, and rarely central nervous system. Most of the systemic
      LYG were shown as Epstein-Barr virus-associated, T-cell-rich, B-cell
      proliferative disorder. Based on radiological and pathological characteristics,
      we analyzed LYG-suspected four cases. The MRI features of LYG showed multiple
      punctate or linear enhancements that reside along the perivascular space.
      Pathologically, some cases showed borderline malignancy different from malignant
      lymphoma. LYG will be determined more clearly by the gene rearrangement studies
      in addition to radiological and immunohistochemical verifications, which will
      serve as indications for detection of monoclonality, further prognosis and
      therapy.

PMID- 12784685
TI  - [The neurology training in the United States and Japan].
AB  - The practice of neurology, like many other fields of medicine, currently faces a
      number of critical problems in the United States mostly by cumbersome
      restrictions designed to contain rapidly escalating medical costs. Fortunately,
      however, the residency training has maintained the spirit of the time-tested
      tradition, which has served the medical community well ever since its inception
      in 1910. The system has continued with little modifications after a switch of
      internship to Basic Residency Program (PG1) in the late 1960s. In comparison, the
      neurology training in Japan suffers from following deficiencies: 1) a paucity of
      bedside teaching in most medical schools, necessitating the initiation of
      unprepared residents into patient care; 2) an insufficient number of staff,
      especially at a governmental school, precluding an adequate coverage of
      neurological subspecialities such as electrophysiology and neuropathology; 3)
      absence of a tutorialship from senior to junior residents, and from interns to
      medical students, mostly for the lack of organization and logistics; and 4) no
      incentive to specialize without board certification by the governmental agencies
      or proper recognition by insurance providers. We must address these fundamental
      issues to promote neurology as an independent discipline for improved care of
      patients with neurological disorders.

PMID- 12784686
TI  - [Postgraduate education of neurology (PGEN) in Japan].
AB  - PGEN in USA consists of a 3-year well-organized program. This includes 18 months'
      in-patient service, and 12 months' rotation to various electives, also providing
      various conferences and lectures. Residents are salaried, so that they are able
      to concentrate on learning neurology. After completing the residency, the
      majority of the residents appear to enter their private practice. In contrast,
      PGEN in Japan does not have a determined period of training, and residents here
      are not salaried enough, so that they have to do part-time jobs to make their own
      living. This prevents our residents from concentrating on learning neurology. A
      rotation system is also difficult to be established in Japan because of the lack
      of manpower and subspecialists, and tight time schedule partly because of the
      part-time jobs. Although an affective domain as one of the educational objectives
      has been ignored in Japan, we should pay more attention to this domain to educate
      residents to good neurologists. It is also important to encourage staffs to be
      actively involved in the postgraduate education. In order to do this, we should
      evaluate their teaching achievements for their promotion appropriately, and
      senior staffs are required to organize the educational environments.

PMID- 12784687
TI  - [Problems in neurologic specialty training in Japan; a personal view].
AB  - Since started as a newly established department in a medical school fourteen
      years ago, my role as a clinician and teacher/investigator has been hampered by
      several problems; one is only five full-time faculty members available, simply
      too small in number, the lack of specialists in neurophysiology, neuropathology
      and neuroimaging diagnosis in the school, and regularly irregular annual
      enrollment of residents. Those problems, yet not fully solved, have been in part
      overcome by the intradepartmental efforts; that is, to run all the
      electrophysiology works by us, to have the neuropath lab of our own and to read
      all the neuro-images in our own conferences. It is certainly ideal and efficient,
      if the persons specialized to the fields teach residents how to run and read. In
      my experience, however, I had no chance of performing a needle EMG when a
      resident. In contrast, our approach to let all the residents expose to necessary
      procedures, of course under the supervision, may have a great impact on the
      resident's learning experience. It is my recommendation, if I can, that in
      training examination be done 2-3 years prior to the neurology board, the
      subspecialty training course needs to be more comprehensive, covering the entire
      basic and clinical subjects in one full week or so, and our Neurology Association
      eases the passing rate of neurology board exam (currently between 30-60%), when
      the association figures out the number of neurologists necessary in Japan for
      next 10-20 years. The tough exam has certainly served a role of producing well
      qualified neurologists, which we are proud of. However, our young trainees in
      neurology require something else, that is, to touch and feel the patients,
      electrodes, specimens and neuro-images by themselves. Then, one will be able to
      perform the role of a fully practice-oriented neurologist, wherever he has to
      work.

PMID- 12784688
TI  - [A questionnaire survey of the neurology training program in Japan].
AB  - A questionnaire survey was performed in order to see the current trends of the
      neurology training program in Japan. A questionnaire was sent out to 81 neurology
      program directors of the medical schools and large hospitals. 72 program
      directors answered the questionnaires. According to the summed results, each
      program had an average of 37 inpatient beds, 7 teaching staffs with the neurology
      board certification. The program had an average of 4 residents annually, and they
      served as junior neurology residents for 1.8 years, and as chief residents for 1
      year with 6 months of hospital consultation. 1.4 years training in the internal
      medicine was prerequisite for the neurology program. The training of clinical
      neurophysiology was done mainly by the own faculty staff in each program, but the
      training of neuroradiology and neuropathology varied. A quarter of the training
      programs had their own teaching staffs of neuroradiology and the rest of three
      quarters asked for training to the neuroradiology department. 32 of 72 programs
      had their own teaching neuropathologists and 26 programs asked the training in
      the pathology department and 14 programs did not have any teaching staffs of
      neuropathology. It seems that these numerical data are quite similar to those of
      the American standard of Accreditation Councils. We must still improve the real
      contents of the neurology training program with more capable teaching staffs.

PMID- 12784689
TI  - [Intracerebral grafting of cell line or patient-derived neural stem cells for the
      treatment of neurological disorders].
AB  - Due to the development of molecular biology techniques, several types of
      neurotransmitter or neurotrophic factor secreting cell line can be established.
      These cell lines were grafted into the brain of animal models of Parkinson's
      disease and cerebral ischemia after encapsulating into the hollow fiber consisted
      of semipermeable membrane. Immunological reaction and tumor formation were
      prevented and functional effects were observed histologically, chemically and
      behaviorally. Current issues regarding encapsulated cell grafting are: delivery
      of neurotransmitter and neurotrophic factor simultaneously from one capsule,
      usage of human-derived cell lines and control of secretion from outside. There
      are two possible approaches regarding the usage of patient's own neural stem
      cells for regenerative therapy. Neural stem cells are collected from the
      subventricular zone of the lateral ventricle and these cells are differentiated
      into dopaminergic neurons using tyrosine hydroxylase induction cocktail (TH
      cocktail). Then, these neurons are grafted into the striatum of the patient.
      Another method is to inject TH cocktail into the patient's striatum in order to
      induce differentiation of dopaminergic neurons from the neural stem cells in
      vivo.

PMID- 12784690
TI  - [Ethical questions of the human embryonic stem cells research].
AB  - With the "Guidelines for Derivation and Utilization of Human Embryonic Stem
      Cells" of September 2001, Japan has become one of few countries that officially
      permit the research on human ES cells. The decision to permit such research is
      based on a well balanced consideration between the advantages towards the new
      medicine and the disadvantages of destroying the embryo who has a potential of
      life. The main ethical concern is the respect for human dignity and human rights.
      The whole ethical consideration comes from this standpoint, and the Guidelines
      set out the conditions to be respected in each research project. Because of its
      potential for human life, the embryos for the derivation of human ES cells, for
      which only frozen supernumerary embryos may be used, should be treated with full
      respect of its dignity. The ES cells themselves should also be used with full
      respect accordingly. Obtaining informed consent from the donors with possibility
      of withdrawal is the most important procedure. The import of human ES cells is
      also possible if similar conditions are fulfilled in the country of derivation.
      Each research project is put under a double check system, first by the IRB and
      then the Experts Committee on governmental level.

PMID- 12784691
TI  - [Provisional diagnostic criteria of corticobasal degeneration (CBD) and the
      survey of patients with CBD in Japan].
AB  - We conducted the survey of patients with CBD in 2001 for 29 neurological
      institutions in Japan which joined Research Group on Neurodenerative Diseases
      supported by Ministry of Health and Welfare. Provisional diagnostic criteria of
      CBD were as follows: "probable CBD" means a clinical category including (1)
      classical form, consisting of progressive limb-kinetic apraxia and akinetic
      rigidity, predominant on one side, associated with late dementia, (2) quasi
      classical form, revealing other corticobasal signs, predominant on one side,
      associated with late dementia, and (3) non-classical from, showing early aphasia,
      dementia, behavior disorder, etc., followed by lateralized limb-kinetic apraxia
      and akinetic rigidity. "Possible CBD" was not made. "Definite CBD" is
      pathologically confirmed CBD. There were 151 patients with "probable CBD",
      comprising 121 patients with classical form, 17 with quasi-classical form and 13
      with non-classical from, while patients with "definite CBD" were 13. The number
      of patients with progressive supranuclear palsy (PSP) was also examined. The
      ratio of the number of patients CBD/PSP was 1/2.6 in clinical cases and 1/2.5 in
      autopsy cases. Nakashima et al. performed population survey of PSP patients in
      Yonago city in 1999, demonstrating prevalence of PSP 4.36/100,000. Considering
      this rate, the prevalence of CBD is assumed as 1.7 and the presumed number of PSP
      and CBD patients in 1999 in Japan could be 5,500 and 2,100, respectively.

PMID- 12784692
TI  - [Neuropathological features in corticobasal degeneration and progressive
      supranuclear palsy].
AB  - Corticobasal degeneration (CBD) is a sporadic neurodegenerative disorder of late
      life with a range of clinical presentations such as progressive asymmetrical
      rigidity and apraxia, progressive aphasia or dementia. Focal cortical atrophy,
      ballooned neurons and degeneration of the substantia nigra and globus pallidus
      have been emphasized in previous descriptions. Recent immunohistochemical studies
      revealed that tau-positive neuronal and glial lesions in both gray and white
      matter, especially astrocytic plaques in the affected cerebral cortex, are the
      characteristic features in CBD. While cortical involvement is also recognized in
      progressive supranuclear palsy, ballooned neurons are sparse and limited to the
      paralimbic areas and tufted astrocytes are abundant in the precentral gyrus and
      striatum. From a neuropathological viewpoint, CBD is distinct from other sporadic
      tauopathies.

PMID- 12784693
TI  - [Neuroimaging features in progressive supranuclear palsy and corticobasal
      degeneration].
AB  - Progressive supranuclear palsy (PSP) and cortocobasal degeneration (CBD) are
      often clinically confused with each other. In this paper, based our previous and
      on-going morphological and functional neuroimaging studies, the features
      characteristic of the two diseases are discussed. In PSP patients, the atrophic
      and metabolic changes are dominant in the frontal lobes, basal ganglia, and
      midbrain, while in CBD patients, the changes are dominant in the parietal lobe.
      There is little overlap of topographical distribution of atrophy and functional
      changes between PSP and CBD, despite the considerable similarity of symptoms of
      the two disorders. The clear distinction between the two diseases may be in part
      caused by the criteria-based subject selection process; based on stringent
      clinical diagnostic criteria for each disorder, which have a high specificity and
      a low sensitivity, only patients that are typical of each disease are compared.
      Nevertheless, these neuroimaging features appear to reflect different clinical
      and pathologic phenotypes between the two diseases. These findings suggest that
      neuroimagings facilitate the differential diagnosis between patients with PSP and
      those with CBD.

PMID- 12784694
TI  - [Corticobasal degeneration and progressive supranuclear palsy--biochemical
      marker].
AB  - The diagnostic significance of tau proteins in cerebrospinal fluids (CSF) has
      been described in many cases of dementia of Alzheimer type (AD). However, in
      patients with other diseases showing neurofibrillary tangles (NFT) similar to
      those in AD, tau proteins in cerebrospinal fluids have not been rigorously
      investigated. In particular, differentiating corticobasal degeneration (CBD) and
      progressive supranuclear palsy (PSP) is clinically and pathologically difficult,
      and a useful biochemical marker to discriminate these two diseases has been a
      subjects of clinical interest. Therefore, we examined the usefulness of CSF tau
      and amyloid beta (A beta) proteins for the differentiation between CBD and PSP.
      CSF total tau (t-tau) and A beta proteins were measured with the sandwich ELISA
      method (Innogenetics, Belgium). CSF tau protein phosphorylated at serine 199 (p
      tau) was measured by a recent established sandwich ELISA (Mitsubishi Chemical
      Co.). In conclusion, measurement of tau protein levels in CSF may be useful for
      the differential diagnosis of CBD from PSP. We also suggest that CSF p-tau may be
      a better biochemical marker than CSF t-tau.

PMID- 12784695
TI  - [EBM in acute stroke].
AB  - Evidence-based medicine (EBM) has been emphasized in Japan for these years. In
      management of acute stroke, prospective stroke registries and randomized
      controlled trials have provided evidence that helps us examine and treat patients
      with acute stroke. The author advocates five important key words, DRUGS, for
      establishing the EBM in stroke management in Japan; 1) Stroke Data Bank, 2)
      Randomized Controlled Trials (RCT), 3) Stroke Unit (SU), 4) Guidelines and 5)
      Stroke Scales. Unfortunately evidence in the five key words has always been
      imported into Japan from the Western countries. We have to create the basis of
      the EBM in acute stroke management by establishing a Stroke Data Bank, confirming
      the effects of potential therapies with RCTs, spreading SUs to major hospitals,
      publishing guidelines for acute stroke management, and using stroke scales in our
      daily clinical practice.

PMID- 12784696
TI  - [Guidelines for the management of stroke].
AB  - For the evidence-based management of stroke, the first guideline was produced at
      1994 from the American Heart Association, and also at 2000 from the United
      Kingdom. However, there is no such guidelines created in Japan yet. Due to the
      differences in therapeutic agents, disease subtypes, and races between our and
      other countries, we must create our own guidelines, taking into consideration of
      the evidences and situations from/in Japan. In this presentation, we addressed
      the following issues; 1) Historical overview regarding the evidence-based
      guidelines for the management of stroke. 2) Details about the Japan Joint
      Committee on Guidelines for the Management of Stroke (Chairman: Yukito Shinohara,
      Secretary-General: Masao Nagayama) which was established in October 2000 with the
      initiative of stroke-related societies in Japan. 3) Analysis of the
      recommendations and literatures describe-cited in the first draft of the
      Guidelines and the Evidence tables. 4) Problems and future directions in the
      therapeutic research of stroke management.

PMID- 12784697
TI  - [Japan stroke scales and its application for stroke].
AB  - There are many stroke scales currently available for estimating the severity and
      outcome of stroke. However, none of the stroke scales have been able to
      objectively quantify the severity of stroke. The Japan Stroke Society formed a
      subcommittee to task force the development of an innovative, quantifiable stroke
      scale. Conjoint analysis was utilized to compile this data. Finally, they
      developed a novel, and quantifiable Japan Stroke for the acute phase of stroke
      (JSS) (Stroke 32: 1800-1807, 2001). In addition to standard JSS, the Japan Stroke
      Scale Motor Function and Japan Stroke scale--Higher Cortical Function were
      finalized. These stroke scales are all parametric stroke scales. We utilize the
      stroke scales to monitor stroke patients, to start clinical pathway on patients
      with lacunas infarction after deciding whether severity of stroke is suitable for
      the clinical pathway by JSS. We use the JSS for the clinical studies of stroke
      patients. Furthermore, the JSS was utilized in the phase 2 trial of a new
      treatment in stroke patients which had significant statistical power. The scales
      were also introduced to the stroke databank. Therefore, these scales are useful
      to monitoring the neurological damage of stroke patients in the acute and chronic
      phase and to estimating the severity of stroke symptoms and predicting stroke
      outcome in clinical studies. They also have a potential to prove the efficacy of
      treatments through parametric analysis.

PMID- 12784698
TI  - [Data bank project for acute stroke patients].
AB  - Stroke is the second cause of death within major adult disease and the first
      cause of functional disability for elderly in Japan. The diffusion rate of MRI is
      the highest in the world. Even though, there is only few evidence for stroke
      management has been reported from Japan. It is necessary to make a data bank of
      acute stroke patients as infrastructure making evidence for standardization of
      stroke management. We made Japan standard stroke registry study supported by
      ministry of health and welfare for 3 years. We completed computerized registry
      system and accumulated about 8,000 acute stroke cases from 45 stroke center
      hospitals. This system is also functioning as a stroke database for each
      hospital. From the analysis of the distribution of stroke subtype, the incidence
      of atherothrombotic infarction and cardiogenic embolism was similar to lacunar
      infarction as shown in Fig. 1. Furthermore, the 38% of ischemic stroke patients
      admitted within 3 hours. Thrombolytic therapy was performed in 15% of the
      patients who admitted within 3 hours and their initial severity were NIHSS 6-29.
      The outcome of the patients treated with thrombolytic therapy was significantly
      better than those without it. These data indicate that the stroke data bank
      should be useful tool to make verification of the guideline and planning of
      clinical trial for EBM.

PMID- 12784699
TI  - [Internet: an infrastructure of evidence-based medicine in neurology].
AB  - EBM is a cyclic process. Medical evidences are created in clinical trials, which
      are published in medical literatures. The medical literatures are converted to
      literature database, from which clinical practice guidelines are made. They are
      provided to the clinicians, from whom a new clinical research is born again.
      Information technology, especially the use of internet has deeply related to
      every process of EBM, which is shown above. In clinical trials, data are
      accumulated through internet and the process is controlled by a coordinator using
      internet. In Japan, University Hospital Medical Information System (UMIN) has
      successfully provided such a tool to the clinical researchers. For the literature
      search. IT is mandatory and clinical practice guidelines are created on the base
      of various secondary information database, which are edited using advanced
      information technology Clinical practice guidelines are provided to hospitals
      through internet and they reach to the clinicians using a function of hospital
      information system, especially electronic medical record. In recent days, IT is
      an indispensable tool for daily practice of evidence-based medicine. However, in
      Japan the evidence has not been accumulated in national level, and for the
      future, the creation of national database of medical data should be explored.

PMID- 12784700
TI  - [Search and appraisal of literatures and methods to use Internets in evidence
      based neurology].
AB  - A national guideline for stroke management is currently being made on the basis
      of evidence collected from randomized controlled trials (RCTs) and other types of
      clinical studies, which have been searched using computer system, as well as
      systematic reviews by the Cochrane Collaboration. In this guideline, grades of
      recommendation will be determined according to the levels of evidence. In
      critical appraisal for clinical trials, evaluation of validity in the methodology
      of trials and in the analysis of treatment effects are crucial. In estimating the
      quality of metaanalysis, a pivotal issue is to check the possibility of selection
      bias in RCTs. Indices for the assessment of treatment effects include relative
      risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat
      (NNT). Besides, cost-effectiveness, cost-benefit, and cost-utility are used in
      medical economics. Quality-adjusted life years (QALY) and disability-adjusted
      years (DALY) have recently been proposed by the World Health Organization as the
      indices for the effect on quality of life as well.

PMID- 12784701
TI  - [Application of the information technology for critical path and neurointensive
      care unit].
AB  - An effectiveness of neurointensive care unit for the treatment of neurological
      diseases and an application of the information technology (IT) for this and a
      critical pathway were discussed. A critical pathway is useful to make a
      standardized treatment, to reduce the days in hospital and to obtain an informed
      consent. But the hospital information system should include the critical pathway
      in itself otherwise doctors have to make duplicated order to nurses and the
      hospital ordering system.

PMID- 12784702
TI  - [On-line outcome study of unruptured cerebral aneurysm in Japan (UCAS Japan)].
AB  - Information technology has been introduced in the medical field recently, and has
      become an essential tool for medical research in many aspects. Japanese
      Neurosurgical Society has been conducting a national study on the outcome of
      unruptured cerebral aneurysms (UCA) using on-line registration system. In this
      report, the author reports preliminary outcome of this study and discuss the
      usefulness and limits of studies using such technology. This study is a
      prospective cohort study and enrolled patients are cases with newly diagnosed UCA
      after Jan. 1,2001. So far, we have collected data of 2979 new patients (3667
      aneurysms) with UCA registered from 385 institutions. Seventy five percent of the
      institutions sent data through the online registration. On-line registration
      system made data collection from all over the country very quick and easy.
      Analyzing such data could be achieved with minimal cost and time. Such study
      design can eliminate the handicap of geographic distance and can be applied for
      international studies. On the other hand, such system does not suit complicated
      study or rare disease. And On-line study design requires special consideration on
      various scenario and uniformity in assessing inclusion, procedure and outcome.

PMID- 12784703
TI  - [Overview of the clinical forms of multiple sclerosis in Japan].
AB  - The clinical course of MS may follow a variable pattern over time, and a clinical
      classification has been defined into three categories: relapsing-remitting,
      secondary progressive, and primary progressive. More recently, from the stand
      point of therapeutic utility, a new classification system including clinically
      isolated syndrome, relapsing MS, secondary progressive MS, and primary
      progressive MS. The optico-spinal MS (OS-MS) is characterized by a female
      preponderance, a later onset, milder abnormalities on brain MRIs, and is
      positively associated with DPB1*0501, indicating that the OS-MS is
      immunogenetically as well as clinically a distinct subtype of MS. Conventional MS
      is also heterogeneous especially in disease course, HLA associations, and CSF
      findings. MS is one clinical entity of idiopathic inflammatory demyelinating
      diseases (IIDD) of the CNS. However, the classifications of the IIDD seem to
      quite different even between the specialists for MS research. We should try to
      get a consensus for the classifications of IIDD, and for the clinical entity
      "MS".

PMID- 12784704
TI  - [Pathogenesis of optic-spinal MS].
AB  - We reviewed the clinical and immunological features of optic-spinal multiple
      sclerosis (OSMS), or relapsing neuromyelitis optica. OSMS has collected much
      attention as to whether it is a distinct entity from conventional MS (CMS).
      However, OSMS plus minor cerebral and brainstem/cerebellar involvement and the
      later conversion into CMS had been a diagnostic dilemma. To overcome such
      problems and delineate the features of OSMS, we analyzed 'Pure OSMS' with which
      patients had only relapsing optic neuritis and myelitis clinically and
      consistently normal brain MRI during 5 years or longer follow-ups. As a result,
      we found that this type of MS was characterized by a definite female
      preponderance and negative oligoclonal IgG bands (OB), although 'Pure OSMS' was
      heterogeneous with regards to the clinical severity and HLA class II alleles.
      Previously reported immunological data in OSMS include negative OB and no
      elevation of IL-10 or matrix metalloproteinase-9 in the cerebrospinal fluid (CSF)
      during relapses. In addition, we recently demonstrated that the CCR5+ Th1 cell
      subset in CSF during relapses, which significantly increased in CMS, remained low
      in OSMS. These unique clinical and immunological findings probably relate to
      fundamental differences in the pathogeneses of OSMS and CMS and deserve further
      characterization.

PMID- 12784705
TI  - [Molecular immunogenetic approach to the pathogenesis of multiple sclerosis].
AB  - In Japanese, there is no association of susceptibility to multiple sclerosis with
      any HLA class II alleles as a whole group. However, when we clinically classified
      MS patients into those having opticospinal form MS which presented selective
      involvement of the optic nerve and spinal cord and those with conventional form
      MS showing multiple involvement of the central nervous system including cerebrum,
      cerebellum and brainstem, the former showed a significant association with HLA
      DPB1*0501 allele while the latter had an association with HLA-DRB1*1501 allele.
      The patients with opticospinal form MS showed a marked Th1/Tc1 shift both in the
      relapse phase and in the remission phase, as determined by an intracellular IFN
      gamma/IL-4 ratio in peripheral blood CD4+ T cells and CD 8+ T cells. These
      findings suggest that opticospinal form MS is also an organ-specific autoimmune
      disease associated with a distinct HLA allele. By using SEREX method and brain
      proteomics approach, we have thus searched for any relevant autoantigens in the
      central nervous system in Japanese patients with MS. Heat shock proteins and
      neural proteins are found to be possible new candidate autoantigens in Japanese
      patients with MS.

PMID- 12784706
TI  - [Hypothetical view on the environmental factors, Th1/Th2 balance, and disease
      phenotype of MS/EAE].
AB  - The optico-spinal form of multiple sclerosis (MS) seems to be no more predominant
      in Japan. Instead, the proportion of the conventional MS is as large as that seen
      in Caucasian population, probably due to the change in life style or
      environmental factors. Here I discuss on the environmental factors that might
      have influenced on the change in the disease phenotypes. It is reasonable to
      speculate that Japanese people are now exposed to antigens that were not
      prevalent 30 years ago. The "new" antigens may cross-stimulate autoimmune T cells
      that are responsible for forming demyelinating lesions in the brain but not in
      the spinal cord. On the other hand, the young Japanese might have missed
      encountering certain bacterial antigens in the childhood that is necessary to
      establish the properly balanced T cell repertoire. The modern Japanese is
      reported to have the immune repertoire that is relatively Th2-biased. The Th2
      shift may account for the more frequent development of the conventional MS in the
      young Japanese. To support this idea, I point out that the mice that tend to
      mount a Th2 response would develop brain lesions after induction of EAE, whereas
      the Th1 mice would develop spinal cord lesions.

PMID- 12784707
TI  - [Current aspects of lung transplantation in eastern countries and Japan].
AB  - Approximately 1,500 lung transplantations are performed as an established
      treatment for progressive benign pulmonary diseases in Eastern countries. In
      Japan, however, lung transplantation has just started after a long dark period
      since the transplant law had become effective in October, 1997. Until today, 33
      patients underwent lung transplantation, of whom 13 were received from brain
      death donors and 20 from living donors. For the patients in Kyushu, this
      therapeutic modality would be also expected in this district.

PMID- 12784708
TI  - [Primary and secondary prevention of coronary artery disease].

PMID- 12784709
TI  - [A case of Fitz-Hugh-Curtis Syndrome representing hepatic capsular enhancement].
AB  - We present CT findings of a 22-year-old woman diagnosed as Fitz-Hugh-Curtis
      syndrome. The patient was admitted to our hospital with right upper abdominal
      pain. Abdominal enhanced CT showed hepatic capsular enhancement over the medial
      segment and the right lobe on the early phase. This capsular enhancement
      completely disappeared after treatment. Abdominal enhanced CT may serve as a non
      invasive modality for the diagnosis of Fitz-Hugh-Curtis syndrome.

PMID- 12784710
TI  - [Clinical evaluation of ureteral endometriosis: report of 8 cases].
AB  - We report 8 cases of ureteral endometriosis. The mean age of the 8 patients was
      42 years (range 29 to 60). In all patients, endometrial lesions were located in
      the lower third of the ureter and were unilateral. Six patients presented with
      flank pain and in one of the 6 cases the pain was associated with menses. One
      presented with gross hematuria. One had no symptoms. Seven out of 8 cases had
      gynecological diseases and 4 had had surgical treatment for the gynecological
      diseases. Four patients were treated with gonadotropin-releasing hormone (Gn-RH)
      analogue for hydronephrosis of endometriosis. In 2 patients, the therapy was
      effective, but hydronephrosis recurred. Surgical therapy was done on all
      patients. We recommend surgical therapy for hydronephrosis with ureteral
      endometriosis.

PMID- 12784711
TI  - [Long-term efficacy of naftopidil for treatment of lower urinary tract symptoms
      with benign prostatic hyperplasia].
AB  - Naftopidil was administered to 67 patients with benign prostatic hyperplasia
      (BPH) for 12 months. Changes in total/each International Prostate Symptom Score
      (IPSS) for irritative and obstructive symptoms, nocturia, and residual urine
      volume were compared before and after its administration. As a result, a
      significant decrease of score was found in total-IPSS, obstructive and irritative
      symptoms, which also showed a tendency to decrease at the end of the first month.
      Nocturia and residual urine volume also significantly decreased after its
      administration. Naftopidil is considered to be effective in the treatment of BPH,
      especially irritative symptoms including nocturia in treatments for BPH, because
      both irritative and obstructive symptoms (IPSS subjective endpoints) and residual
      urine volume (objective endpoint) were improved after its long-term
      administration.

PMID- 12784712
TI  - [Interstitial laser coagulation for benign prostatic hyperplasia: clinical
      results of the Indigo diode laser system].
AB  - We report our experience with interstitial laser coagulation of the prostate
      (ILCP) using an Indigo 830j diode laser system for benign prostatic hyperplasia
      (BPH). From March 1998 to November 2000, we treated 45 patients between 51 and 95
      years old (average 71.5) with symptomatic BPH. The mean prostatic volume before
      ILCP was 62.0 cm3. We experienced no serious complications. Three months after
      ILCP, the mean international prostate symptom score (I-PSS) quality of life (QOL)
      index and post-void residual volume (PVR) decreased significantly from 18.0 to
      9.2, from 4.4 to 2.1 and from 103.6 ml to 44.5 ml, respectively. The mean maximum
      flow rate (MFR) increased from 7.6 ml/sec at baseline to 9.2 ml/sec 3 months
      after ILCP, but the difference was not statistically significant. Before and
      after ILCP, 8 patients were available to evaluate pressure-flow study data. The
      detrusor pressure at the maximum flow rate decreased significantly from 118.3
      cmH2O at baseline to 78.6 cmH2O 3 months after ILCP. The improvement of the I
      PSS, QOL index, MFR and PVR continued and at 24 months reached 5.7, 1.8, 11.6
      ml/sec and 54.6 ml, respectively. In our assessment of the questionnaire
      addressing the patient's satisfaction after the treatment, the majority of the
      patients who answered the questionnaire were pleased with the results of ILCP. We
      assessed the relation of the overall treatment efficacy with the number of
      punctures and the total amount of the laser energy delivered, but we did not find
      any relation. Our clinical results suggest that the ILCP using Indigo 830j is an
      effective modality and the short-term treatment efficacy is favorable.

PMID- 12784713
TI  - [Extrarenal retroperitoneal epithelioid angiomyolipoma: a case report].
AB  - We present a very rare case of retroperitoneal extrarenal epithelioid angio
      myolipoma (AML). A 64-year-old man without tuberous sclerosis was admitted to our
      hospital for further examination of an abdominal mass lesion. Imaging analyses
      revealed a heterodensity and heterointensity retroperitoneal mass covering the
      left renal surface by ultrasonography, computed tomography and magnetic resonance
      imaging. Surgical exploration was done, and the tumor was resected with the left
      kidney radically. Histopathologically high cellular atypia was remarkable, and
      diagnosis was extrarenal epithelioid AML because of consistent immunostaining
      positive for HMB-45.

PMID- 12784714
TI  - [Serious renal infection: report of three cases].
AB  - In renal infections, lack of peculiar symptoms and consequent delay of diagnosis
      can sometimes lead to a critical condition of the patient. We report three cases
      of life-threatening renal infections in female patients, two of which were
      subsequently fata. One patient died of left emphysematous pyelonephritis with
      bilateral pleuritis. The patient was correctly diagnosed 13 days after the onset
      of symptoms and expired 2 months later despite nephrectomy on the day of
      diagnosis. The second patient died of septic shock 3 days following the onset of
      symptoms. Autopsy revealed multiple perinephric abscess of the left kidney. The
      non-fatal case was a perinephric abscess spread to the iliopsoas muscle. The
      patient was diagnosed with perinephric abscess 11 days after the onset of
      symptoms and eventually underwent nephrectomy 9 days later. Two of the patients
      were diabetics and the third was a probable diabetic, who died too suddenly to
      confirm the diagnosis. Herein, we review the literature of, and discuss the
      diagnosis and management of serious renal infection.

PMID- 12784715
TI  - [Epidermoid cyst of the testis difficult to make a preoperative diagnosis on the
      echoic examination: a case report].
AB  - A case of epidermoid cyst of the testis is presented. The patient was a 64-year
      old man who complained of a painless mass in the left scrotum. Physical
      examination revealed a hen-egg sized enlargement of the left scrotal contents.
      The ultrasonographic appearance did not show a hyperechoic partition, which is
      called echogenic rim, a characteristic of this tumor on the echoic examination,
      and was homogeneous, almost similar to that of a normal testis. Because malignant
      testicular tumors could not be excluded preoperatively, excisional biopsy of the
      left testis was performed first. Histological diagnosis was an epidermoid cyst of
      the testis. As the left testis was almost completely occupied by the tumor and no
      normal testicular tissue was recognized, we performed orchiectomy additionally.
      Epidermoid cyst of the testis is a rare benign tumor that accounts for about 1
      percent of all testicular tumors. It clinically resembles malignant testicular
      tumors, and orchiectomy is often performed for treatment. About 154 cases of
      testicular epidermoid cyst have been reported in the Japanese literature and are
      reviewed briefly here.

PMID- 12784716
TI  - [A mixture of transitional cell carcinoma and adenocarcinoma of the renal
      pelvis].
AB  - An 85-year-old male was admitted to our hospital with the chief complaint of a
      left hydronephrosis. Computed tomography (CT) revealed left hydronephrosis and a
      left ureteral tumor. We performed left nephroureterectomy. Microscopically, the
      neoplasm was composed of a mixture of transitional cell carcinoma and
      adenocarcinoma. To our knowledge, this case is the 14th report of mixed carcinoma
      of the upper urinary tract.

PMID- 12784717
TI  - [A case of renal cell carcinoma metastasizing to the contralateral kidney and
      renal pelvis].
AB  - Extremely rarely renal cell carcinoma metastasizes to the contralateral renal
      pelvis or ureter. A 42-year-old man had undergone left radical nephrectomy for
      renal cell carcinoma (pT1b, grade 2) in March, 2000. Fifteen months later, he
      complained of macroscopic hematuria. Computed tomographic scanning and retrograde
      pyelography showed a right renal pelvic tumor. Enucleation of pelvic tumor was
      performed and a parenchyma mass incidentally identified in the right kidney was
      also resected. Histopathological examination of each tumor revealed renal cell
      carcinoma identical to the primary tumors in the left kidney suggesting
      metastasis to renal pelvis and de novo tumor or metastasis in the right kidney.

PMID- 12784718
TI  - [A case of complete regression of metastatic renal cell carcinoma following
      corticosteroid treatment].
AB  - A 72-year-old man presented with hemosputum and was admitted to our hospital.
      Computed tomography and osseous scintigraphy revealed right renal cancer and
      multiple pulmonary and osseous metastases. A translumbar nephrectomy was
      performed. The histopathological examination demonstrated granular cell carcinoma
      and clear cell carcinoma. The patient complained of dyspnea on postoperative day
      (POD) 16, and chest X-ray showed progression of the multiple pulmonary metastases
      and lymphangitis carcinomatosa. Betamethasone was administered for palliative
      treatment. After the treatment, dyspnea improved and chest X-ray on POD 57 showed
      disappearance of the multiple pulmonary metastases and improvement of
      lymphangitis carcinomatosa. Computed tomography and osseous scintigraphy
      confirmed complete regression of metastases. He has been free from recurrence for
      16 months after the nephrectomy and for 13 months after the complete regression.
      To our knowledge, this is the first case of complete regression of metastatic
      renal cell carcinoma following corticosteroid treatment reported in Japan, and
      the second case when foreign literature is included.

PMID- 12784719
TI  - [Spermatocele associated with cholesterol crystals].
AB  - A 53-year old man first recognized swelling of the left scrotum five years ago.
      Ultrasound examination revealed spermatocele, consisted of two layers, fluid area
      and hyperechoic sediment. Cloudy fluid containing a large amount of cholesterol
      crystals was aspirated from the spermatocele. To the best of our knowledge, this
      case is the first spermatocele with cholesterol crystals in the Japanese
      literature.

PMID- 12784720
TI  - A case of organized scrotal hematocele with high serum CA19-9 level.
AB  - A 67 year-old male consulted our department for examination a painless left
      scrotal mass accompanied by a continuously high serum carbohydrate antigen 19-9
      level (CA19-9, 563.2 IU/ml). The patient underwent radical orchiectomy oof the
      mass. The histopathological diagnosis was an organized hematocele, and left
      testicular tissue was found in the cyst wall. There was no evidence of malignancy
      in the cyst wall or cyst contents, and immunohistochemical analysis showed no
      CA19-9-positive cells. However, the CA19-9 level lowered to the normal range
      immediately after surgery. The patient's CA19-9 level has remained normal, with
      no recurrence of tumor to date. Considering the clinical course, we suspected the
      resected mass to have been the cause of the high serum CA19-9 level, and to our
      knowledge, this is the first case report of organized hematocele in the scrotum
      with a high CA19-9 level.

PMID- 12784721
TI  - [A case of prostate cancer with cyst formation].
AB  - We treated a case of prostate cancer with cyst formation in an 80-year-old
      Japanese man presenting with constipation. Fist-sized elastic soft mass was
      palpable by digital rectal examination. Computed tomography and magnetic
      resonance imaging demonstrated a retrovesical cystic mass arisen from the
      prostate. Serum prostate-specific antigen (PSA) was elevated to 15.7 ng/ml.
      Transrectal prostate needle biopsy revealed moderately differentiated
      adenocarcinoma and puncture of the cyst yielded aseptic bloody fluid. With a
      clinical diagnosis of prostate cancer (T2b N0 M1b) with cystic formation,
      hormonal therapy with a luteinizing hormone releasing hormone analogue and
      bicalutamide significantly lowered the serum PSA level. One year later, the cyst
      was reduced in volume and constipation had resolved. A total of 57 cases of
      prostate cancer with cyst formation are reviewed.

PMID- 12784723
TI  - [Intraocular tumor--recent advances in differential diagnosis].

PMID- 12784722
TI  - [Renal cell carcinoma in acquired cystic disease of the kidney manifested by
      spontaneous renal rupture].
AB  - A 67-year-old male had been maintained on hemodialysis for 13 years because of
      chronic renal failure secondary to diabetes mellitus. The patient was referred to
      our hospital with sudden right flank pain. Computed tomography revealed multiple
      cysts in both kidneys and a right massive perirenal hematoma. Although there was
      no definite evidence of a renal tumor, a right nephretomy was performed.
      Histological study revealed acquired cystic disease of the kidney (ACDK) with a
      hematoma containing papillary renal cell carcinoma. He has been free of
      recurrence for 2 months. To our knowledge, this case is the fourth report of
      renal cell carcinoma in ACDK manifested by spontaneous rupture in the Japanese
      literature.

PMID- 12784724
TI  - [Early clinical results of laser epithelial keratomileusis].
AB  - PURPOSE: To evaluate the efficacy of laser epithelial keratomileusis (LASEK).
      SUBJECTS AND METHOD: LASEK was performed on 82 eyes of 42 patients whose
      spherical refraction ranged from -0.75 to -12.00 D (mean, -6.09 D) and
      cylindrical refraction ranged from 0 to -5.00 D (mean, -0.95 D). LASEK is a
      method of making a epithelial flap using 20% ethanol and repositioning the flap
      after excimer laser ablation. The clinical results of postoperative refraction
      and complications were examined. RESULTS: At 1 week and 1 month after the
      operation, 69 eyes(84.1%) and 79 eyes(96.3%) achieved an uncorrected visual
      acuity of 20/20 or better. At 1 week and 1, 3 months after the operation, the
      mean spherical refraction was +0.09 +/- 0.49(mean +/- standard deviation) D,
      +0.29 +/- 0.47 D, +0.13 +/- 0.46 D. At 1 month 65 eyes (79.3%) were within +/-
      0.5 D and 78 eyes(95.1%) were within +/- 1.0 D. 51 eyes (62.2%) had the
      complication of corneal haze. CONCLUSION: LASEK achieved good uncorrected visual
      acuity, but there were some complications such as postoperative pain, the delayed
      recovery of visual acuity, and corneal haze, so that a long and careful follow-up
      seems necessary.

PMID- 12784725
TI  - [Reduction of asthenopia-related to accommodative relaxation].
AB  - PURPOSE: We investigated experimentally the effect of accommodative relaxation by
      outward shift stimuli for accommodation on asthenopia. METHODS: Twenty female
      students fixed on optical outward-shift stimuli at accommodation for 2 min
      immediately after 15 min of a sustained task on a 3-D display. Before and after
      the trial task and the outward shift stimuli, their accommodative step response
      was measured and their subjective symptoms were assessed. The outward shift
      stimuli in the optical system, which was set on a refractometer, were presented
      by moving the target scenery images from far to near and near to far repetitively
      a round both eyes' far point position. At the same time as the accommodation
      measurements, the changes of refraction were recorded from the same eye. RESULTS:
      While looking at the outward shift stimuli, the refraction of 9 out of 20
      subjects showed an outward shift and that of the other 11 subjects shifted
      inward. The post-trial value of contraction (from far to near) time of
      accommodative step response in the inward-shift group was markedly prolonged,
      from 0.86 s to 0.97 s (p = 0.043), and the post-trial accommodative power at the
      far target was shifted outward; from +1.21 D to +1.13 D(p = 0.048). The
      subjective symptoms of "ocular fatigue", "eye heaviness" and "eye dryness" also
      increased after the is(p = 0.0035, p = 0.0038, p = 0.0162, respectively). In the
      outward-shift group, however, no statistical changes were found. CONCLUSION: From
      these results, we suggested that accommodative relaxation produced by outward
      shift stimuli at accommodation is effective in reducing of asthenopia following
      the deterioration of accommodative functions.

PMID- 12784726
TI  - [Pathophysiology and diagnosis of congenital periodic alternating nystagmus].
AB  - PURPOSE: Not many cases of congenital periodic alternating nystagmus have been
      reported in Japan. We investigated the pathophysiology and diagnosis of
      congenital periodic alternating nystagmus noting the age when this disease began,
      which had not been reported previously. SUBJECTS: Ninety-one patients with
      congenital nystagmus who were seen in our department in Teikyo University School
      of Medicine between July 1994 and January 2002 were studied. RESULTS: Eighteen
      patients(19.8%) among the 91 congenital nystagmus patients were diagnosed with
      congenital periodic alternating nystagmus. A manifestation of the periodic face
      turning was seen between the age of three and nine. Visual acuity over 0.6 with
      correction was obtained in all patients. Almost all the patients had an
      asymmetric cycle of null point shifting and the face turning was seen at one side
      for a long time. CONCLUSION: When we see congenital nystagmus patients whose face
      turning alters periodically with fairly good vision over the age of three, we
      must check out the direction of jerk nystagmus changes at the same gazing point
      using electronystagmography or video cassette recording to detect the possibility
      of congenital periodic alternating nystagmus.

PMID- 12784727
TI  - [Natural killer-cell lymphoma of the iris with a normal fundus].
AB  - BACKGROUND: Intraocular lymphoma is a relatively uncommon malignancy, rarely
      presenting with exclusively anterior segment findings in a normal fundus. CASE: A
      38-year-old male, previously diagnosed with nasal lymphoma, currently in complete
      remission after chemotherapy and radiotherapy, presented with blurring of vision
      in his left eye, which initially responded to local steroid therapy. However, the
      patient developed resistance to steroid therapy and developed nodular masses in
      the left iris. Ultrasound biomicroscopy revealed diffuse thickenings leading to a
      complex and uneven shape of the left iris. An iris biopsy was done which led to
      the diagnosis of natural killer(NK)-cell lymphoma. Radiation therapy was
      instituted which led to rapid resolution of both the nodular masses and iritis.
      CONCLUSION: This is a case of malignant lymphoma presenting as metastasis to the
      iris without involvement of the chorioretinal tissues. When encountering a
      patient with iritis resistant to the steroid therapy, clinical ophthalmologists
      should consider metastatic malignancy in the differential diagnosis.

PMID- 12784728
TI  - [Choroidal melanoma complicated with central retinal vein occlusion].
AB  - BACKGROUND: Various complications for choroidal melanoma have been reported.
      However, there are no reports on choroidal melanoma complicated with central
      retinal vein occlusion. CASE REPORT: A 37-year-old male showed an elevated
      yellowish white tumor of about 8 discs in diameter, and involving the optic disc
      in the left eye. Serous retinal detachment and subretinal exudate were noted
      around the tumor. Central retinal vein occlusion occurred concurrently.
      Fluorescein angiography revealed blocks due to hemorrhage and fluorescence
      leakage from the retinal vein. Dilation of retinal capillary vessels and marked
      leakage of fluorescence from the retinal vein and capillary vessels were found in
      the tumorous region. In the late stage, the entire tumor presented hyper
      fluorescence. On indocyanine green angiography, the tumor on the whole presented
      hypo-fluorescence from the early to late stage, and an insular hyper-fluorescence
      suggestive of the presence of intratumor vessels with leakage of fluorescence was
      seen inside. Ultrasonography revealed choroidal excavation. General examination
      showed no abnormality. On the basis of these findings the patient was diagnosed
      with choroidal melanoma. CONCLUSION: We report a case of choroidal melanoma,
      which was complicated with central retinal vein occlusion by mechanical
      compression and invasion of the optic disc from the first medical examination.

PMID- 12784729
TI  - [A case of intraocular malignant lymphoma diagnosed by immunoglobulin gene
      rearrangement and translocation, and IL-10/IL-6 ratio in the vitreous fluid].
AB  - BACKGROUND: The diagnosis of primary intraocular lymphoma is difficult in many
      cases even with conventional cytological tests using vitreous samples. Recently
      new diagnostic tests, such as microdissection and polymerase chain reaction (PCR)
      and measurement of cytokines using intraocular samples, have been applied to the
      diagnosis of the disease. We report here a case where we used the new diagnostic
      tests and the results aided us to make a diagnosis of intraocular lymphoma. CASE:
      A 68-year-old woman with an initial diagnosis of bilateral idiopathic uveitis
      with steroid-resistant vitreous opacities underwent a vitreous biopsy. The
      cytological examinations of the vitreous samples revealed class III. The
      microdissection and PCR using the vitreous samples detected IgH rearrangement
      gene in the third framework (FR3A), the complementary determining region 3 (CDR3)
      of the VH region and Bcl-2-associated translocation. The interleukin (IL)-10 to
      IL-6 ratio in the vitreous fluid was greater than 100. Because the results of the
      examinations strongly suggested intraocular lymphoma, the patient was treated
      with radiation and chemotherapy. One month after the therapy, however, the
      patient developed multiple metastatic lesions in the brain. The clinical course
      of the patient together with the new diagnostic results of examinations led to a
      diagnosis of intraocular lymphoma. CONCLUSION: A combination of tests, such as
      conventional cytology, microdissection, and PCR, and cytokine assay using
      intraocular biopsy samples, is useful to make a diagnosis of intraocular
      lymphoma.

PMID- 12784730
TI  - [New insights into neural mechanisms controlling the micturition reflex].
AB  - The functions of the lower urinary tract, to store and periodically release
      urine, are dependent on the activity of smooth and striated muscles in the
      bladder, urethra, and external urethral sphincter. This activity is in turn
      controlled by neural circuits in the brain, spinal cord, and peripheral ganglia.
      During urine storage, the outlet is closed and the bladder smooth muscle is
      quiescent. When bladder volume reaches the micturition threshold, activation of a
      micturition center in the dorsolateral pons (the pontine micturition center)
      induces a bladder contraction and a reciprocal relaxation of the urethra, leading
      to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves
      provide an excitatory input (cholinergic and purinergic) to the bladder and
      inhibitory input (nitrergic) to the urethra. The brain rostral to the pons
      (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory
      regulation of the micturition reflex. Various transmitters including dopamine,
      serotonin, norepinephrine, GABA, excitatory and inhibitory amino acids, opioids,
      acetylcholine, and neuropeptides are implicated in the modulation of the
      micturition reflex in the central nervous system. Therefore, injury or diseases
      of the nervous system, as well as drugs and disorders of the peripheral organs,
      can produce bladder and urethral dysfunctions such as urinary frequency, urgency
      and incontinence, or inefficient bladder emptying.

PMID- 12784731
TI  - [Regulation by autonomic nerves of bladder neck sphincter function--mainly on
      inhibitory NANC nerves].
AB  - This article describes current information concerning analyses of contraction and
      relaxation associated with electrical stimulation of efferent nerves in isolated
      mammalian sphincter muscles. Contractile responses of sphincters are mediated by
      alpha 1-adrenoceptors and muscarinic receptors stimulated by transmitters from
      adrenergic and cholinergic nerves, respectively, whereas those of the bladder
      body are almost exclusively mediated by transmitters from parasympathetic nerves.
      Relaxant responses to nerve stimulation are ascribed mainly to mechanisms that
      are sensitive and resistant to nitric oxide (NO) synthase inhibitors. Neurogenic
      calcitonin gene-related peptide and beta-adrenoceptor activation by neurogenic
      norepinephrine may also be involved in some mammals. Stimulus frequency is an
      important determinant to distinguish NO synthase-sensitive and -resistant
      components; responses at low frequencies are abolished by the enzyme inhibitors,
      whereas those at high frequencies are inhibited only partially. High and low
      frequency stimulation increases the cyclic GMP content in muscles, suggesting the
      involvement of neurogenic NO, although relaxation at high frequencies is only
      partially due to such a mechanism. From pharmacological studies so far analyzed,
      including ours performed with porcine urinary tract sphincters, it is concluded
      that NO synthase resistant-relaxation is not mediated by peptides nor compounds
      that open K+ channels in muscle cell membrane and stimulate beta-adrenoceptors.
      Contribution of NO and non-NO relaxing factor (s) in relaxant responses varies
      with animal species. Identification of this factor, determination of
      intracellular signaling processes and interaction with the NO/cyclic GMP system
      may give us a clue in developing new therapeutics to treat dysfunctions of the
      lower urinary tract sphincters.

PMID- 12784732
TI  - [Pharmacological analysis of neurotransmitters contributing to lower urinary
      tract function].
AB  - Lower urinary tract function is controlled by the autonomic nervous system, which
      consists of adrenergic, cholinergic, and non-adrenergic, non-cholinergic (NANC)
      neurons. We have measured the amount of various neurotransmitters (acetylcholine,
      ACh; noradrenaline, NA; adenosine triphosphate, ATP; and nitric oxide, NO)
      released from human and rabbit urinary tract smooth muscles by the microdialysis
      method coupled with HPLC. Muscle strips are isolated from human or rabbit
      bladder, urethra, and prostate. A microdialysis probe was inserted into each
      smooth muscle strip. Each muscle strip was connected to an isometric transducer,
      and tension development was measured. We have evaluated the changes in electrical
      field stimulation-induced neurotransmitter releases and functional responses in
      physiological and pathological conditions and the interactions between
      neurotransmitters or neurons. In this review, we present several of our results:
      1) interactions between adrenergic and nitrergic neurons in rabbit urethra, 2)
      effect of NO on human bladder function, 3) effect of NO on human prostate
      function, and 4) effects of aging on acetylcholine and ATP releases from human
      bladder smooth muscles. These data may reveal physiological or pathological
      neurotransmitter control of lower urinary tract function and give us useful
      information for clinical intervention to treat lower urinary tract symptoms.

PMID- 12784733
TI  - [Molecular and electrophysiological investigation of ATP-sensitive K+ channels in
      lower urinary tract function: the aims for clinical treatment of unstable
      detrusor].
AB  - It is a common sequelae of bladder outlet obstruction caused by benign prostatic
      hyperplasia in adult males and gives rise to significant bladder dysfunction such
      as frequency and urgency of micturition. The unstable detrusor contractions may
      lead to urge incontinence. Since it has been reported that experimentally-induced
      bladder instability can be abolished by ATP-sensitive K+ channel (KATP channel)
      openers, various types of detrusor-selective KATP channels have been newly
      synthesized, targeting KATP channels in urinary bladder. Thus, the significant
      differences in molecular and pharmacological properties of KATP channels between
      urinary bladder and urethra hold out some hope for the development of tissue
      selective KATP channel openers for urge urinary incontinence, and detrusor
      selective KATP channel openers should be screened against urethral as well as
      vascular smooth muscle. In functional expression experiments, pharmacological and
      electrophysiological studies have reported that SUR1/Kir6.2 represents the
      pancreatic beta-cell KATP channel and that SUR2A/Kir6.2 is thought to represent
      the cardiac KATP channel, whereas SUR2B/Kir6.1 represents the smooth muscle-type
      KATP channel. In general, the smooth muscle type-KATP channel is (i) of a
      relatively small conductance (about 20 pS under quasi-physiological conditions,
      approximately 40 pS in symmetrical 140 mM K+ conditions), (ii) intracellular
      Ca(2+)-insensitive, (iii) inhibited by intracellular ATP, (iv) abolished by
      glibenclamide at a submicromolar concentration, and (v) reactivated by
      intracellular nucleoside diphosphates (NDPs). There has been no report concerning
      the properties of KATP channels in human detrusor by use of single-channel
      recordings. We would like to introduce our recent evidence of novel synthesized
      detrusor-selective KATP channel openers and properties of KATP channels in the
      lower urinary tract.

PMID- 12784734
TI  - [Molecular biological researches of the lower urinary tract function].
AB  - Adrenergic alpha1 and beta receptors are present in the target organs of
      sympathetic nerve and they participate in the signal transduction mechanism of
      the lower urinary tract. Adrenergic alpha1 receptors are present in urethral and
      prostatic smooth muscles, and contract these muscles. Among these receptor
      subtypes, the alpha1-A receptor has the most important role, and mRNA expression
      of the corresponding alpha1-a subtype is predominant. In the human urinary
      bladder detrusor smooth muscle, the expression of adrenergic beta3 receptor
      subtype mRNA is predominant, and relaxation of detrusor smooth muscle is mediated
      mainly via beta3 receptor. Afferent nerve with lower threshold can easily
      transmit bladder sensation and takes an important role in the pathophysiology of
      urge urinary incontinence. Successful molecular cloning of vanilloid receptors,
      which are present in these afferent nerves, revealed that vanilloid receptors are
      ion-channels, sensitive for heat and pH, and termed VR1 and VRL1. Among
      purinergic receptors, ion channel type P2X3 receptor is found in afferent nerve
      fibers and plays some roles in the signal transduction of bladder sensation. In
      the near future, agonist for the adrenergic beta3 receptor and selective
      antagonists for VR1, VRL1, or P2X3 will possibly become drugs for pollakisuria
      and urge urinary incontinence.

PMID- 12784735
TI  - [Pathophysiology of the overactive bladder and its pharmacological treatment].
AB  - This paper reviews the possible mechanisms underlying bladder overactivity and
      discusses the targets for pharmacological treatment of this disorder. Damage to
      the brain (cerebrovascular disease, etc.) induces bladder overactivity by
      reducing suprapontine inhibition. Currently, attention has focused on C-fiber
      bladder afferents that may concern the mechanisms for bladder overactivity
      resulting from various etiologies such as spinal cord lesions, bladder outlet
      obstruction and bladder hypersensitivity disorders. With regard to the
      pathophysiology of idiopathic overactive bladder, both myogenic and neurogenic
      mechanisms may be involved in involuntary detrusor contraction. Since an
      intravesical capsaicin or resiniferatoxin was shown to have favorable therapeutic
      effects, afferent C-fiber neurons become a new target for pharmacological
      treatment. C-fiber neurons are known to contain tachykinins and other peptides as
      neurotransmitters. When released, tachykinins can influence via NK receptors
      bladder activity. In addition, evidences suggest that ATP receptors (P2X3) and
      prostaglandin receptors in afferent C-fiber neurons may play a role in mediating
      bladder overactivity. Thus, NK-antagonist, P2X3-antagonist and PG receptor
      antagonist may be potential therapeutic drugs in the near future. beta 3
      Adrenoceptor agonist is an another candidate drug for the treatment of the
      overactive bladder. Finally, it is important to notice that in any etiology
      including an idiopathic one, antimuscarinic drugs can improve bladder
      overactivity, although dry mouth and constipation are inevitable side-effects.

PMID- 12784736
TI  - [Na+ overload-induced mitochondrial dysfunction in myocardial
      ischemia/reperfusion injury].
AB  - An accumulation of Na+ is induced in the ischemic myocardium, which is so-called
      "Na+ overload". The exact role of Na+ overload in the genesis of myocardial
      ischemia/reperfusion injury remains unclear except for the role as a driving
      force of Ca2+ overload in the reperfused myocardium. Excessive activation of
      Na+/H+ exchanger (NHE) and Na+ channels may contribute to Na+ influx into the
      ischemic myocardium, resulting in sodium overload under ischemic conditions. A
      decrease in energy-producing ability of mitochondria in the ischemic myocardium
      is also observed in an ischemic duration-dependent manner. Attenuation of Na+
      overload by an NHE inhibitor or a Na+ channel blocker preserved mitochondrial
      energy production in the ischemic myocardium and enhanced post-ischemic
      contractile recovery. To mimic Na+ overload in the ischemic myocardium, isolated
      mitochondria were incubated with sodium lactate, a possible end product of
      anaerobic glycolysis. Sodium lactate induced an irreversible reduction in the
      mitochondrial energy production. The mitochondrial damage induced by sodium
      lactate was not attenuated by the NHE inhibitor or the Na+ channel blocker,
      suggesting that these agents may indirectly preserve mitochondrial function in
      the ischemic myocardium. Taken together, Na+ overload in the ischemic myocardium
      may induce mitochondrial dysfunction, leading to contractile failure of the
      reperfused myocardium.

PMID- 12784737
TI  - [Real-time detection of neurotransmitter release and its spatial distribution].
AB  - Neurotransmitters have been well known as information carriers for a long time.
      Recently, some of the research indicated their neurotoxicity, while some
      indicated their neurotrophic actions. It is very important to understand the role
      of neurotransmitters. Glutamate is one of the most important excitatory
      neurotransmitter in the brain. We developed a novel measurement method for
      glutamate. The method we describe here is based on the enzyme-mediated
      electrochemical detection. Glutamate oxidase and horseradish peroxidase were
      deposited together with polymer-mediator on the electrode. We applied this idea
      on ITO multi-array electrode and developed a 64 channel multi-array sensor. The
      sensor permits us to detect glutamate release from multiple regions
      simultaneously in real time. As it is possible to illustrate the distribution of
      glutamate release, the sensor could be used not only in the pharmacological
      field, but also in medical treatment in the near future.

PMID- 12784738
TI  - [Real-time imaging of local Ca2+ signaling in single neurons].
AB  - In addition to the multiple mechanisms of the intracellular calcium mobilizing
      pathways, neurons possess multiple functional compartments such as the soma, the
      axon, the dendrites, and the spines. In this article, technical procedures and
      tips are described to measure local calcium signaling in response to neuronal
      excitation in single neurons.

PMID- 12784739
TI  - Is a syncope a syncope?

PMID- 12784740
TI  - Digoxin therapy for heart failure: safe for women?

PMID- 12784742
TI  - Atrioventricular nodal reentrant tachycardia: anatomical and electrophysiological
      considerations.
AB  - Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common
      regular narrow QRS tachycardias. Although the principal understanding of the
      physiology of dual atrioventricular conduction as a substrate for the reentry
      mechanism in AVNRT has not changed during the last 25 years, there is still some
      uncertainty with regard to the exact circuit delineation. At least four forms of
      AVNRT have been described and several possible circuits have been proposed.
      Although the refinement of our knowledge about AVNRT seems to be purely academic
      since further insight will probably not increase the success rate of treatment by
      radiofrequency catheter ablation, AVNRT continues to puzzle both clinical and
      basic electrophysiologists. The authors summarize our present knowledge about
      AVNRT and stress the unique features of the atrioventricular junction anatomy and
      the current opinions on the reentrant impulse propagation.

PMID- 12784741
TI  - Cardiac-bio-assists: biological approaches to support or repair cardiac muscle.
AB  - In contrast to those of other cardiac diseases, the morbility and morbidity of
      congestive cardiac insufficiency are not on the decrease, in spite of significant
      progress in pharmacological treatments and due to the increased life expectancy
      of the population. Cardiac transplant is the therapy of choice when cardiac
      failure becomes pharmacologically intractable, but all over the developed world
      (not to mention the situation in the underdeveloped countries) the number of
      heart transplants has reached the limit set by the availability of donor organs.
      Sooner or later xenotransplants could solve this problem, but even if our most
      optimistic hopes regarding their development and reliability are met,
      xenotransplants would still carry the risk of anthropozoonotic viral infections.
      Finally, as suggested in a recent overview, the way to the long-lasting clinical
      use of mechanical circulatory support is a long and winding road. Other options
      are related to tissue or cell cardiac bioassistance. Cardiac-bio-assists are
      biological approaches to the remedy of progressive cardiac failure based on
      autologous or heterologous tissue or cell transplantation. Some of the work
      hypotheses are in pre-clinical evaluation (skeletal muscle ventricle), others are
      under preliminary (cardiomyoplasty, myocardium reduction, implants of myoblasts
      derived from skeletal muscle satellite cells and implants of embryonic or adult
      stem cell-derived myocardiocytes, cellular cardiomyoplasty) or advanced clinical
      testing (dynamic aortomyoplasty and dynamic cardiomyoplasty). Dynamic
      cardiomyoplasty is a surgical procedure which could support myocardial function
      when cardiac insufficiency would become pharmacologically intractable in the mid
      term. In this procedure a nonessential muscle, the latissimus dorsi (LD), is
      diverted from its normal role, transferred into the chest, wrapped around the
      heart (LD wrap), conditioned to fatigue and activated during systole to provide
      cardiac assistance. The mechanisms of its action are discussed and the risk of
      myodystrophic lesions of the LD wrap which could reduce the work capability of
      the pericardial muscle prosthesis remains. We are now addressing some of these
      issues by means of clinical research on the group of Italian patients of demand
      dynamic cardiomyoplasty, and by means of animal experiments aimed at the
      development and testing of new surgical, clinical and biotechnological
      approaches. In particular, we will discuss whether the increase in the muscle
      mass of the distal part of the transposed LD is desirable and feasible or if it
      is mandatory.

PMID- 12784743
TI  - Noninvasive assessment of left and right internal mammary artery graft patency
      using transthoracic color Doppler echocardiography.
AB  - BACKGROUND: The aim of this study was to evaluate the patency of left and right
      internal mammary artery grafts respectively on the left anterior descending and
      right coronary artery by noninvasive transthoracic color Doppler
      echocardiography. METHODS: Thirty eight patients (34 males, 4 females, mean age
      59 +/- 2 years), with a history of coronary artery bypass grafting for a total of
      42 mammary artery grafts, were studied by means of color Doppler echocardiography
      at baseline and after vasodilation with dipyridamole infusion (0.56 mg/kg i.v.
      over 4 min). The evaluated echocardiographic parameters included: systolic (SPV)
      and diastolic peak velocities (DPV), systolic (SVI) and diastolic velocity-time
      integrals (DVI), and the DPV/SPV and DVI/SVI ratios. We also calculated the
      dipyridamole infusion to baseline ratio of the diastolic peak velocities
      (DPVdip/DPVbaseline), the index of internal mammary artery graft blood flow
      reserve and the percent DPV increment as an index of graft stenosis. RESULTS: On
      the basis of coronary angiography, two groups were selected: group A (36 mammary
      grafts) with patent grafts and group B (6 mammary grafts) with moderate or severe
      stenosis of the grafts. Group A had a predominant diastolic pattern with a DPV of
      0.24 +/- 0.13 m/s, whereas group B had a predominant systolic pattern with a
      reduced DPV of 0.12 +/- 0.03 m/s (p < 0.01). Dipyridamole induced an increase in
      the DPV respectively of 86.8 +/- 64.4% in group A and 13.8 +/- 15.9% in group B
      (p < 0.001). Statistical analysis (Mann-Whitney test) revealed a significant
      difference between the two groups for the baseline DPV (p < 0.01), DVI (p <
      0.05), DPV/SPV ratio (p < 0.005), DVI/SVI ratio (p < 0.05), and for the after
      dipyridamole infusion values: DPV (p < 0.0001), DVI (p < 0.005), DPV/SPV ratio (p
      < 0.001), and DVI/SVI ratio (p < 0.05). Multivariate analysis showed that the
      percent DPV increment, the DPVdip/DPVbaseline ratio and the baseline DPV were
      independent determinants of the stenosis as evaluated at angiography (beta = 
      0.38, p < 0.01; beta = -0.37, p < 0.01, and beta = -0.33, p < 0.05, respectively;
      cumulative r2 = 0.25, standard error 0.30 m/s, p < 0.005). CONCLUSIONS: The
      echocardiographic evaluation of the mammary grafts is a simple, noninvasive
      method for the assessment of the graft patency and of the functional status of
      the vessel. The percent DPV increment and baseline DPV were independent
      determinants of mammary graft stenosis.

PMID- 12784745
TI  - Respiratory changes in transvalvular flow velocities versus two-dimensional
      echocardiographic findings in the diagnosis of cardiac tamponade.
AB  - BACKGROUND: The purpose of this study was to compare the sensitivity, specificity
      and positive predictive value of the respiratory changes in the transvalvular
      flow velocities to those of right atrial collapse and right ventricular collapse
      in the diagnosis of cardiac tamponade. METHODS: Standard two-dimensional and
      Doppler echocardiography were performed with respiratory monitoring in 56
      consecutive patients with mild to severe pericardial effusion. Sixteen patients
      met the clinical criteria for cardiac tamponade and underwent pericardiocentesis
      or surgical drainage. Forty patients were found to have no tamponade and were
      followed up for at least 2 weeks and none of them showed clinical worsening.
      RESULTS: The sensitivity, specificity and predictive value were, respectively,
      77, 80 and 62% for an inspiratory decrease > 22% in the peak velocity of the
      early mitral flow; 75, 89 and 73% for an inspiratory reduction > 20% in the peak
      velocity of the aortic flow; 50, 69 and 36% for an inspiratory increase > 30% in
      the peak velocity of the early tricuspid flow; 87, 85 and 64% for an inspiratory
      increase > 25% in the peak velocity of the pulmonary flow. Right atrial collapse
      and right ventricular collapse had a sensitivity of 100 and 75%, a specificity of
      33 and 85%, and a predictive value of 37 and 66%, respectively. CONCLUSIONS: In
      the diagnosis of cardiac tamponade: 1) right atrial collapse is the most
      sensitive sign but lacks any specificity; 2) except for the tricuspid valve, the
      respiratory variations in the transvalvular flow velocities have a reliability
      and a predictive value comparable with those of right ventricular collapse; 3)
      the predictive value is not very high, indicating that at both techniques false
      positive results are not negligible.

PMID- 12784744
TI  - Myocardial Doppler at rest for the identification of myocardial viability.
AB  - BACKGROUND: Echocardiography may permit the detection of a nonviable myocardium.
      The aim of this study was to test if resting pulsed wave-tissue Doppler imaging
      (PW-TDI) might yield additional markers. METHODS: Fifty patients (38 males, 12
      females, mean age 63 +/- 6 years) with left ventricular dysfunction (ejection
      fraction 35 +/- 10%) underwent echocardiography. The posterior septum, anterior
      septum, lateral, inferior, anterior and posterior walls were sampled on the basal
      segments in the apical views at PW-TDI. The following variables and cardiac
      phases were tested: 1) the isovolumic contraction phase velocity, polarity or
      detectability, 2) the ejection phase velocity, a detectable interval between the
      ejection phase and aortic valve closure, or ejection phase shape, and 3) the
      isovolumic relaxation phase velocity or ejection velocity/post-systolic
      shortening ratio. From the tested PW-TDI variables, viable and nonviable patterns
      were assembled, taking rest-redistribution 201thallium single-photon emission
      computed tomography as the independent reference for myocardial viability.
      Patients with significant loading alterations, mitral or aortic valve disease,
      and arrhythmias were excluded. RESULTS: Out of 219 dyssynergic segments,
      viability as identified according to conventional rest echocardiographic criteria
      appeared in 94 (47%), as identified at PW-TDI in 116 (53%), and as identified at
      nuclear imaging in 105 (48%). The resting PW-TDI variables consistent with absent
      myocardial viability were as follows: 1) an isovolumic contraction phase velocity
      equal to the ejection phase velocity +/- 1 cm/s, or absent, 2) an ejection phase
      velocity < or = 4 cm/s, usually with a gap between the ejection phase and aortic
      valve closure, or any shape of ejection but the typical single phase, and 3) an
      isovolumic relaxation phase velocity < 5 cm/s with an ejection phase
      velocity/isovolumic relaxation phase velocity ratio < 0.8. The accuracy for the
      identification of myocardial viability was: agreement 73%, kappa 0.44 for
      echocardiography, and agreement 75%, kappa 0.47 for PW-TDI. CONCLUSIONS: PW-TDI
      nonviable patterns may be a helpful additional tool for the identification of
      patients without residual myocardial viability.

PMID- 12784746
TI  - In-hospital clinical outcome in elderly patients with acute myocardial infarction
      treated with primary angioplasty.
AB  - BACKGROUND: The aim of the present study was to assess the early clinical outcome
      following primary coronary angioplasty in elderly patients (aged > or = 75 years)
      compared to younger patients (< 75 years). METHODS: The study population included
      655 consecutive patients (mean age 61.5 +/- 12.4 years) with acute ST-elevation
      myocardial infarction (MI) who underwent primary percutaneous coronary
      intervention (PCI) within 12 hours of symptom onset. Elderly patients accounted
      for 14.5% (96 of 655) of all patients. Primary PCI was performed using a balloon
      and/or coronary stent as well as glycoprotein IIb/IIIa inhibitors. The primary
      endpoint was the in-hospital incidence of major adverse cardiac events (including
      death, stroke, reinfarction, target vessel revascularization and new onset of
      heart failure). RESULTS: Elderly patients were more frequently female (48 vs 20%,
      p < 0.001) and had more comorbid disease (prior stroke 7.2 vs 2.5%, p < 0.05) and
      more extensive cardiovascular disease (previous acute MI 13.5 vs 5.5%, p < 0.05;
      multivessel disease 71.8 vs 44.6%, p < 0.0005) and a significantly lower ejection
      fraction (48 vs 50%, p < 0.05). Despite a similar rate of TIMI 0-1 flow at
      presentation (69 vs 74%, p = NS), a similar use of stents (84 vs 86%, p = 0.3)
      and of glycoprotein IIb/IIIa inhibitor infusion (19.8 vs 22.1%, p = 0.3) and a
      comparable angiographic residual stenosis (21 vs 19%, p = NS), the final rate of
      TIMI 3 flow was significantly lower in the elderly population (77.8 vs 91.4%, p <
      0.001). Although the in-hospital ischemic event rates for all ages were not
      significantly different, the in-hospital mortality was higher in the elderly as
      compared with younger patients (9.3 vs 3.2%, p < 0.0001), even when the patients
      with cardiogenic shock at the time of admission were excluded (4.4 vs 0.9%, p <
      0.0001). Furthermore, more patients aged > or = 75 had in-hospital heart failure
      (5.2 vs 1.8%, p < 0.05). In the whole population, multivariate analysis
      identified baseline Killip class III-IV as the only independent predictor of
      events. In elderly patients, multivariate analysis identified baseline Killip
      class III-IV and the time from the onset of chest pain to PCI as independent
      predictors of events. CONCLUSIONS: Our data suggest that in elderly patients with
      acute ST-elevation MI primary PCI yields positive results: successful reperfusion
      can be achieved in a high proportion of elderly patients and the mortality rates
      are lower, than those reported in non-PCI registries. A high Killip class and
      late reperfusion therapy predict an unfavorable outcome in elderly patients
      treated with primary PCI.

PMID- 12784747
TI  - Intracoronary beta-radiation for the treatment of patients at very high risk for
      recurrence of in-stent restenosis: a single center experience.
AB  - BACKGROUND: Intracoronary brachytherapy has significantly reduced the recurrence
      of in-stent restenosis. The aim of this study was to evaluate the feasibility,
      safety and efficacy of intracoronary beta-radiation in patients at very high risk
      for recurrence of in-stent restenosis. METHODS: We analyzed 42 patients with 50
      lesions submitted to catheter-based beta-radiation (Beta-Cath System, Novoste
      Corporation, Norcross, GA, USA) for in-stent restenosis. Thirty-eight lesions
      were at the second restenosis, 8 at the third, and 4 at the fourth; a diffuse
      pattern was present in 78%. RESULTS: Balloon angioplasty was performed for 30
      lesions (60%) and the cutting balloon technique for 20 (40%). In 12 lesions
      further 14 stents had to be deployed (28%). The delivery catheter was
      successfully positioned in 96% of the procedures. The mean dwell time was 179 +/-
      50 s with a radiation dose ranging from 18.4 to 25.3 Gy, depending on the vessel
      size. A complete angiographic success without coronary dissection and without any
      additional stenting after radiation delivery was achieved in 86%. At follow-up
      (7.2 +/- 2.1 months), the overall restenosis rate was 30.4% (14 lesions). A
      recurrence was detected in 1/11 lesions with initial focal pattern and in 13/39
      lesions with initial diffuse pattern. The restenosis rate was higher in patients
      in whom a geographic miss had occurred (p < 0.05 vs lesions without geographic
      miss) and in those in whom a new stent had been deployed (p < 0.05 vs lesions
      treated without a stent). CONCLUSIONS: Brachytherapy reduces the in-stent
      restenosis rate in patients who are at very high risk of recurrence. The
      restenosis pattern, geographic miss and new stent deployment seem to be negative
      prognostic factors for recurrence of restenosis.

PMID- 12784748
TI  - Thoracic and abdominal aortic aneurysms: invasive and non-invasive imaging from
      an endovascular perspective.

PMID- 12784749
TI  - Surgical treatment of tricuspid valve dysplasia in the neonatal period.
AB  - Tricuspid valve dysplasia, other than Ebstein's anomaly, is a very rare
      congenital heart defect. During the prenatal and/or the neonatal periods the
      clinical picture is very critical. We here report on a newborn infant with severe
      tricuspid valve dysplasia and 4/4 tricuspid regurgitation, giant right
      atriomegaly, functional pulmonary atresia with ductal-dependent pulmonary blood
      flow. The child was successfully submitted to implantation of a 15 mm pulmonary
      stentless heterograft valve using the top-hat technique.

PMID- 12784750
TI  - Images in cardiovascular medicine. His bundle recording in congenital corrected
      transposition of the great arteries with mirror atrial arrangement (situs
      inversus) and mesocardia.

PMID- 12784751
TI  - Images in cardiovascular medicine. Emergency endovascular repair of abdominal
      aortic graft rupture.

PMID- 12784752
TI  - [Non-invasive assessment of coronary flow reserve with transthoracic
      echocardiography: physiopathology, methodology and clinical value].
AB  - The assessment of coronary flow reserve with transthoracic Doppler
      echocardiography, measured as the ratio between hyperemic and baseline coronary
      flow velocities, is a new tool for the evaluation of coronary artery disease and
      coronary microcirculation. Color-guided pulsed Doppler allows almost optimal
      identification of flow velocities at the middle and distal left anterior
      descending artery and good visualization of the right coronary artery. The
      development of ultrasound technology (second harmonic, contrast agents, dedicated
      softwares) is responsible for great feasibility (until 98% for the left anterior
      descending artery and 40-50% for the right coronary artery) and very good
      reproducibility of this tool. Doppler-derived coronary flow reserve has excellent
      concordance with that obtainable with intravascular Doppler flow wire. Diagnosis
      of stenosis and restenosis after stent implantation in the middle and/or proximal
      left anterior descending artery and of stenosis of the right coronary artery is
      very accurate. In the absence of stenosis of epicardial coronary arteries, the
      reduction in coronary flow reserve implies a damage of coronary microcirculation,
      which can be a determinant of angina pectoris and signs of myocardial ischemia in
      arterial hypertension, diabetes mellitus and coronary X syndrome. Further
      progress may be expected by using myocardial contrast agents for quantitation of
      regional myocardial coronary flow reserve.

PMID- 12784753
TI  - [Evaluation and management of patients with chronic aortic insufficiency].
AB  - The management of patients with chronic aortic insufficiency is an important
      clinical problem someway still open. A correct understanding of the patient
      should take into account the pathophysiology and natural history of the disease,
      as well as the results that can be achieved with medical and surgical therapy.
      This review will focus on the clinical and instrumental parameters that may bring
      to the best therapeutic decision for the individual patient. Definitely the
      management of patients with chronic aortic insufficiency consists mainly in the
      definition of the right time to surgery with the lowest risk and the greatest
      benefit.

PMID- 12784754
TI  - [Antithrombotic prophylaxis in patients with ventricular dysfunction: critical
      review of the literature and new perspectives].
AB  - Recent observational data suggest that mild or moderate heart failure is
      associated with an annual risk of stroke of approximately 1.2%. Indeed, it is
      possible that the major cause of sudden death in chronic heart failure is not
      related to arrhythmias, but to vascular occlusion. Anticoagulation may reduce the
      rate of embolic events, but there is controversy about the mandatory use of
      antithrombotic therapy for all patients with ventricular dysfunction in sinus
      rhythm. At present antithrombotic therapy is indicated only in "high risk"
      subgroups of patients: atrial fibrillation, mobile/protruding/irregular thrombi,
      acute post-myocardial infarction thrombi or a recent history of thromboembolism.
      Actually there is no evidence to recommend the use of aspirin to prevent
      thromboembolism in patients with ventricular dysfunction in sinus rhythm. Further
      trials of both antiplatelet agents and anticoagulation are sorely needed and we
      are waiting for the results of large trials such as the WATCH trial (Warfarin and
      Antiplatelet Therapy in Chronic Heart Failure) and the WARCEF trial (Warfarin
      Versus Aspirin in Reduced Ejection Fraction). The future appears promising due to
      the advent of a new oral direct thrombin inhibitor, ximelagatran, with good
      efficacy and safety profile for the treatment and prevention of thromboembolism.

PMID- 12784755
TI  - [The role of angiotensin II AT1-receptor antagonists in renal and cardiac
      protection in type-2 diabetes mellitus].
AB  - Blood pressure reduction and intensive antihypertensive treatment are effective
      in reducing both microvascular and macrovascular complications in type 2
      diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now
      recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be
      an important goal in the treatment of hypertension and diabetes-related
      complications. The renoprotective role of angiotensin-converting enzyme (ACE)
      inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE
      inhibitors have been deemed more effective than other traditional drugs in
      reducing the onset of overt nephropathy in microalbuminuric patients (secondary
      prevention) but not in reducing renal dysfunction in patients with clinical
      proteinuria (tertiary prevention). Recently, four large trials performed on type
      2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the
      development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL
      studies) and delay the progression of nephropathy towards end-stage renal failure
      in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have
      been deemed more effective in reducing hospitalizations for heart failure
      compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular
      morbidity and mortality compared to conventional therapy (LIFE study) in type 2
      diabetes. In conclusion, ARBs are effective in preventing and delaying renal
      damage in type 2 diabetes. Thus, the recent guidelines for the prevention and
      treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice
      drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in
      secondary prevention, the same as ACE-inhibitors, and are the unique first-choice
      drug in tertiary prevention of end-stage renal failure in type 2 diabetes.
      Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular
      prevention in type 2 diabetes.

PMID- 12784756
TI  - [Profiles of medical malpractice in the prophylaxis of pulmonary
      thromboembolism].
AB  - Deaths caused by pulmonary thromboembolism (PTE) are often of forensic interest,
      due to the frequent preexistence of a traumatic event the suddeness of death, and
      possible professional responsibility. Early diagnosis of vein thromboembolism is
      often difficult. Fatal PTE usually presents itself on an unexpected and large
      scale, chronologically occurring shortly before death and thus irreconcilable
      with any consequent efficacious therapy. Pharmacological prophylaxis, aiming at
      reducing the state of blood hypercoagulability, is the elective therapeutic
      strategy for vein thromboembolism. These are the premises for this work which,
      after a brief pharmacological and clinical description of heparin prophylaxis and
      a review of data emerging from a sample of 24 deaths due to PTE, makes some
      considerations regarding professional responsibility.

PMID- 12784757
TI  - [Combined diagnostic approach to venous thromboembolism with multidetector
      computed tomography].
AB  - BACKGROUND: Multidetector computed tomography (CT) improves scan length and
      spatial resolution. The availability of a single test that allows a comprehensive
      evaluation of the chest and pulmonary arteries, of the deep venous system of the
      abdomen and legs and the hemodynamic impact of pulmonary emboli on the right
      heart could be a new and effective strategy for patients with venous
      thromboembolic disease. We assess a combined study protocol on venous
      thromboembolic disease by multidetector CT. METHODS: Twenty-four patients with
      confirmed acute pulmonary embolism, in stable clinical conditions, underwent
      multidetector CT. After antecubital intravenous infusion of 120 ml of contrast
      medium at a rate of 4 ml/s followed by 30 ml of saline solution a CT of the chest
      was performed using 4 x 1 mm collimation, pitch 1.5 and 500 ms rotation time of
      the X-ray tube; the start delay was checked for each single patient. Indirect CT
      venography study was acquired 150s after starting the infusion using a 5 mm
      section width from the diaphragm to the popliteal zone. We evaluated: 1) the
      presence of intraluminal filling defects in the pulmonary arteries and in the
      deep venous system from the inferior vena cava to the popliteal veins, and 2) the
      presence of right ventricular dilation with a right ventricle/left ventricle
      (RV/LV) ratio > 1. The patients with CT diagnosis of deep vein thrombosis (DVT)
      and and RV/LV ratio > 1 underwent venous compressive ultrasound and/or
      echocardiography. RESULTS: Pulmonary embolism was detected in 12% in the main
      arteries and in 66, 87 and 20% in the lobar, segmental and subsegmental arteries
      respectively. DVT was found in 14/24 (58%) patients with pulmonary embolism
      involving the ileo-femoral district in 14% of the whole group. Thirteen patients
      (54%) showed a volumetric prevalence of the right ventricle on the left
      ventricle. CT data in the presence of DVT and an RV/LV ratio > 1 was confirmed at
      ultrasonography. CONCLUSIONS: Multidetector CT allows to obtain rapidly and in
      one examination useful information about the source and pulmonary involvement of
      venous thromboembolic disease and about the hemodynamic impact on the right
      heart.

PMID- 12784758
TI  - [Is it time to organize a "new " campaign against congestive heart failure?].

PMID- 12784759
TI  - [Myocardial infarction and severe mitral insufficiency. Presentation of an aortic
      fibroelastoma].
AB  - We report the case of a 75-year-old female with atypical chest pain followed by
      non-Q wave myocardial infarction. At coronary angiography and ventriculography
      severe left main stenosis and severe mitral regurgitation were evidenced.
      Transesophageal echocardiography, performed in order to evaluate a possible
      mitral repair, showed an aortic tumor (11 x 14 mm in diameter) attached to the
      commissure between the left and non-coronary cusp, without mitral regurgitation.
      Cardiac magnetic resonance showed a relationship between the tumor and the left
      coronary ostium which explained a paroxysmal mitral regurgitation. The tumor was
      surgically removed and the resulting defect in the aortic leaflet was
      reconstructed with an autologous pericardial patch. The tumor resulted to be a
      papillary fibroelastoma. The clinical course was uneventful.

PMID- 12784760
TI  - [Primary mesothelioma of the pericardium].
AB  - Primary mesothelioma of the pericardium is a rare tumor. It may occur in diffuse
      and localized forms. Most of the pericardial mesotheliomas are multiple or
      diffuse with growth encasing the heart; localized form uncommon. We report a
      diffuse mesothelioma of the pericardium in a 46-year-old fireman. The patient
      underwent a pericardiotomy and biopsy confirmed the diagnosis.

PMID- 12784761
TI  - [Type-A aortic dissection without chest pain in a patient with Clostridium fallax
      infection].
AB  - We describe the case of a 64-year-old patient admitted to our hospital because of
      syncope and suspicion of cardiac tamponade. At admission he had temporary
      alteration of conscience with clinical evidence of sepsis without chest pain.
      There was a mild pericardial effusion in absence of clinical and
      echocardiographic signs of cardiac tamponade. About 36 hours later we found
      evidence of an aortic dissection and in the blood culture an isolation of
      Clostridium fallax that we consider the probable cause of this lesion.

PMID- 12784762
TI  - [Echocardiographic diagnosis of retro-aortic location of a coronary artery with
      an anomalous origin].

PMID- 12784763
TI  - [Open letter to the Italian cardiologists. An invitation to debate].

PMID- 12784764
TI  - [Clinical problems in heart transplant recipients].
AB  - Heart transplantation has become a more and more effective therapeutic strategy
      in severe heart failure patients. An opportune management of the several medical,
      immunological and psychological complications, that may occur during heart
      transplant recipients' life, is mandatory to succeed in this therapeutic
      approach. Indeed, thanks to heart transplantation, recipients may recover from a
      lethal cardiovascular disease, but on the other hand, they may encounter several
      co-morbidities. An optimized management has to involve not only the referring
      Transplant Center, but also the single patient's personal cardiologist and
      general physician. Therefore, the present paper has the educational aim to
      present the most common clinical problems occurring during heart transplant
      recipients' follow-up, by reviewing current literature in the light of the
      experience gained by the Bologna Heart Transplant Unit.

PMID- 12784765
TI  - [Regeneration of infarcted cardiac tissue: the route of stem cells].
AB  - The ventricular remodeling following an acute myocardial infarction generates a
      non-contractile fibrous scare which might provoke cardiac failure. Several
      techniques aimed at recovering myocardial performance through the utilization of
      stem cells have been investigated in these last years. Embryonal stem cells,
      although they are characterized by an elevated differentiation potential, present
      technical and ethical concerns. Thus, most studies have been addressed towards
      adult (somatic) stem cells. Three categories of adult stem cells are now mainly
      investigated: a) satellite cells from skeletal muscle, b) mesenchymal stem cells
      from bone marrow, c) stem cells which are eventually present in the cardiac
      tissue. Skeletal myoblasts, even if they are not able to differentiate in
      cardiomyocytes, can improve cardiac contractility at the level of the fibrous
      scare which substitutes the necrotic area. It is also possible to isolate stem
      cells from bone marrow which can originate several cell lines, among them cardiac
      muscle cells and endothelial cells. Finally, more recent studies have
      demonstrated that resident cardiomyocytes maintain the capability to duplicate:
      therefore, a population of myocardial progenitors might be able to replicate and
      repair the damaged tissue. A deeper investigation of these findings in the
      clinical field could lead to the identification of new therapeutic strategies
      aimed at ameliorating the cardiac performance of the infarcted patients for short
      and long periods.

PMID- 12784766
TI  - [Why are cardiologists to be concerned about obliterating arterial disease of the
      lower leg?].
AB  - Peripheral arterial disease, which is caused by atherosclerotic stenosis or
      occlusion of the leg arteries, is an important manifestation of systemic
      atherosclerosis. The age-adjusted prevalence of symptomatic and asymptomatic
      peripheral arterial disease is approximately 12% in the general population. The
      overall prevalence and incidence of the disease is likely to increase with the
      aging of the population. Peripheral arterial disease is a relatively benign
      condition in terms of local disease. Five years after the diagnosis, 75% of the
      patients remain clinically stable. On the contrary, life expectancy, even in the
      absence of any history of myocardial infarction or ischemic stroke, has decreased
      by 10 years. These patients have approximately the same relative risk of death
      from cardiovascular causes as do patients with history of coronary or
      cerebrovascular disease. Moreover, the severity of peripheral arterial disease is
      closely associated with the risk of myocardial infarction and death from vascular
      disease. The lower the ankle-brachial index, the greater the risk of
      cardiovascular events. Furthermore, peripheral arterial disease is a significant
      independent predictor for cardiovascular mortality also in coronary patients. The
      risk factors associated with peripheral arterial disease are essentially the same
      as for coronary heart disease: older age, cigarette smoking, diabetes mellitus,
      hypertension, and hyperlipidemia. The excess morbidity and mortality for
      cardiovascular disease in these patients has not been fully explained. Patients
      with peripheral arterial disease show a systemic endothelial dysfunction and an
      increase in the serum concentration of activated white blood cells, endothelin,
      and C-reactive protein that may trigger acute coronary syndromes. In peripheral
      arterial disease the functional status is often severely impaired. Peak exercise
      performance has decreased to about 50% of that of age-matched controls,
      equivalent to moderate-severe heart failure. Epidemiological studies support the
      concept that patients affected by peripheral arterial disease, without
      established coronary heart disease, have a coronary heart disease high risk
      equivalent. In spite of this, peripheral arterial disease remains an
      underdiagnosed and undertreated disease. As the role of cardiologists is
      expanding, the purpose of this review was to awaken the clinician to the
      significance of lower limb atherosclerotic occlusive diseases.

PMID- 12784768
TI  - [Feasibility and accuracy of a rapid evaluation of the abdominal aorta during
      routine transthoracic echocardiography].
AB  - BACKGROUND: Mass screening for occult abdominal aortic aneurysm is not realistic
      for the low prevalence of this condition in the general population. Screening in
      a high-risk population, especially during standard echocardiographic examination,
      could be more cost-effective than a separate screening program. The aim of this
      study was to evaluate the feasibility and accuracy of a rapid evaluation
      (examination arbitrary time-limit of 2 min) of the abdominal aorta at the end of
      a routine transthoracic echocardiographic examination. METHODS: One hundred and
      eighty-one male patients (average age 61 years, range 45-79 years) were studied.
      A subgroup of 83 patients was also blindly examined by a radiologist for
      diagnostic accuracy evaluation. RESULTS: Abdominal aortic aneurysm was defined as
      an aortic diameter enlargement > or = 3.0 cm. Sixteen patients were excluded due
      to suboptimal aortic wall imaging or to examination lasting > 2 min (feasibility
      91%). An occult aneurysm was found in 7 patients (3.8%). As regards the
      presence/absence of aneurysms in the subgroup of patients undergoing double
      examination, sensitivity and specificity were 80 and 100% respectively.
      CONCLUSIONS: Rapid evaluation of the abdominal aorta for aortic screening during
      routine echocardiography is highly feasible and accurate without any significant
      prolongation of the examination time and should therefore be routinely performed
      during standard examination.

PMID- 12784767
TI  - [Quality system in cardiology: practical example to develop an organizational
      model for management certification without bureaucracy].
AB  - It is a difficult task to define practical guidelines and a pragmatic achievement
      for the new document of the Italian Ministry of Health for structures of the
      national health system obtaining a quality system according to the ISO 9000
      standard. The present article illustrates the different steps to accomplish the
      quality management in our cardiology department, recently internationally
      certified, and it gives several practical examples of the path followed in the
      different sections of the department to obtain the best management of all the
      Operative Units, identifying customer requests and measuring customer
      satisfaction.

PMID- 12784769
TI  - [Clinical case of significant "reverse remodeling" after cardiac
      resynchronization therapy].
AB  - A 79-year-old man refers to our echocardiolab for a normal follow-up after 2
      years of biventricular pacing. Seven years before the present observation, the
      patient underwent a biological aortic valve replacement for severe valvular
      stenosis in the presence of marked systolic dysfunction of the left ventricle and
      advanced cardiac failure symptoms. The evaluation of the present and past
      clinical and echocardiographic parameters suggests that conventional surgery and
      full medical therapy did not elicit an improvement of both functional and
      clinical parameters, whereas cardiac resynchronization therapy dramatically
      improved in the mid term all the clinical and functional parameters.

PMID- 12784770
TI  - [A case of pseudoaneurysm of the left ventricular lateral wall. Diagnosis and
      surgical treatment].

PMID- 12784772
TI  - Primary angioplasty, instead of thrombolysis, for all patients with acute ST
      elevation myocardial infarction?

PMID- 12784771
TI  - [Simultaneous stenting of the carotid and left main coronary arteries: a case
      report].

PMID- 12784773
TI  - Tolerability of beta-blockers in heart failure: reassurance needed, reassurance
      provided.
AB  - In contrast to widely held perceptions regarding tolerability of beta-blockers in
      heart failure, it is clear that initiation and uptitration is not as complex as
      perceived. In particular, there is no increased risk of intolerance and/or
      worsening of heart failure symptoms with initiation of beta-blocker therapy (at
      least as demonstrated by carvedilol in COPERNICUS). Furthermore, the perceived
      delay in beneficial effects on outcomes is perhaps challenged by the COPERNICUS
      study. Interestingly, all of the above observations appear to hold true in
      patients with advanced disease. Because of the unique history of beta-blockers in
      systolic heart failure, physicians have needed particular reassurance regarding
      the tolerability of these agents. Reassurance regarding tolerability has now been
      definitively provided.

PMID- 12784774
TI  - Low-dose aspirin in the primary prevention of cardiovascular disease: how to
      balance the benefits and the risks.
AB  - The favorable clinical experience with aspirin in the secondary prevention of
      cardiovascular disease, which has now clearly established the indications for the
      use of the drug in this context, has been the driving force behind the extension
      of its use to primary prevention. Here, however, the balance between the benefits
      and risks is substantially different from that of secondary prevention. In view
      of this, health authorities have been more reluctant to approve the generalized
      use of aspirin in primary prevention. We will here review the reasoning which
      should be at the basis of a set of recommendations, as recently expressed by two
      American expert opinion panels.

PMID- 12784775
TI  - Malnutrition, muscle wasting and cachexia in chronic heart failure: the
      nutritional approach.
AB  - Malnutrition, muscle wasting and cachexia are often present in chronic heart
      failure (CHF). However, malnutrition in CHF patients is not always as severe as
      muscle wasting. Data in the literature show that 24% of CHF patients have
      malnutrition (albumin < 3.5 mg/dl) but 68% have muscle atrophy. This apparent
      discrepancy can be explained by considering the metabolic role of the striate
      muscle. In fact, the striate muscle maintains the body metabolic performance by
      continuous exchanges of fuels (amino acids) with the liver. This happens in case
      of malnutrition or starvation. In such situations, glucose is produced by
      gluconeogenesis when amino acids are metabolized in the liver. Malnutrition,
      muscle wasting and the frequent progression through cachexia can be reduced by
      specific therapy such as cytokine and/or catabolic hormone antagonists. This is
      because cytokines and catabolic hormones, with consequent insulin resistance,
      cause muscle wasting. An alternative and/or complementary therapy may be
      exogenous amino acid supplementation. In fact, amino acids: a) are rapidly
      absorbed regardless of pancreatic activity, b) reduce insulin resistance, c)
      induce the hepatic synthesis of anabolic molecules such as growth hormone and
      insulin-like growth factor, and d) modulate the catabolic hormonal-mediated
      effects on adipocytes. Research on the best suitable qualitative and quantitative
      amino acid composition for an alternative and/or complementary therapy is still
      being studied in different research centers.

PMID- 12784776
TI  - Through the drug-eluting stent labyrinth.
AB  - For interventional cardiologists restenosis has represented the main limit for
      the successful long-term treatment of coronary artery disease. The past 2 years
      witnessed the extraordinary results of drug-eluting stents (DES), putting this
      technique at the center stage. The safety and efficacy of sirolimus and
      paclitaxel-eluting stents have been proved in large prospective, multicenter,
      randomized trials (RAVEL, SIRIUS, TAXUS II). It is possible that the introduction
      of DES will lead to substantial changes in the therapeutic and/or the economic
      strategies of the treatment of ischemic coronary artery disease (increase in the
      complexity of patients treated, reduction in surgical indications, growing
      costs). Realizing the potential value of this technology will require the
      successful management of more complex coronary situations (for lesions and
      patients characteristics). Many extreme situations are still unexplored, although
      for some of them studies are currently in progress or already being planned.

PMID- 12784777
TI  - Left ventricular diastolic function in pregnancy-induced hypertension.
AB  - BACKGROUND: Hypertension occurs in some 10% of pregnancies and its effects on the
      left ventricular (LV) morphology and systolic function have been well elucidated.
      Little is known, however, about the changes in LV diastolic function in such a
      condition. The aim of this study was to evaluate the LV diastolic function in
      women with pregnancy-induced hypertension (PIH) using new Doppler
      echocardiographic methods. METHODS: Twenty-two women with PIH (mean age 31.0 +/-
      4.1 years) were examined during the third trimester of pregnancy. Other 15
      normotensive pregnant women (mean age 31.8 +/- 5.7 years, p = NS) were used as
      controls. Doppler parameters of diastolic function included: mitral inflow
      variables, pulmonary venous flow (PVF) variables, M-mode color Doppler of LV
      inflow and pulsed tissue Doppler of the mitral annulus. Furthermore, patients
      underwent an echocardiographic evaluation immediately after delivery and 1 month
      later. RESULTS: PIH women showed an increased E/A ratio and an increase in the
      diastolic forward components of PVF. The ratio of systolic to diastolic time
      velocity integral and the systolic fraction of time-velocity integrals
      subsequently decreased. Women with PIH also presented a significantly increased
      velocity of reversal PVF at atrial contraction, a decrease in the ratio between
      mitral and PVF duration at atrial contraction and a slower flow propagation
      velocity with M-mode color Doppler. LV wall thickness and mass were significantly
      higher in hypertensive pregnant women. In women with PIH the abnormal PVF
      parameters became similar to those of controls immediately after delivery, while
      the E/A ratio, M-mode flow propagation velocity and LV mass did so after 1 month.
      CONCLUSIONS: Hypertension complicating pregnancy significantly affects
      ventricular diastolic filling. These alterations chiefly involve PVF, mitral
      inflow and intraventricular flow propagation velocities. The LV systolic function
      is preserved, in the presence of a transient LV remodeling.

PMID- 12784778
TI  - Early surgical anteroseptal ventricular endocardial restoration after acute
      myocardial infarction. Pathophysiology and surgical considerations.
AB  - BACKGROUND: The efficacy and safety of surgical anteroseptal ventricular
      endocardial restoration (a procedure that excludes non-contracting scarred
      segments) in the left ventricle with chronic dilation and remodeling secondary to
      an anterior myocardial infarction are well established. We present a small series
      and discuss the indication for early left ventricular restoration in the setting
      of complicated acute myocardial infarction. METHODS: Early ventricular
      restoration was performed in 8 patients (4 males, 4 females, mean age 70 +/- 8
      years). A postinfarction ventricular septal defect was diagnosed in 3 cases. All
      patients were operated, on an urgent or emergent basis, between 1 and 16 days
      following the onset of infarction. Surgical coronary revascularization was
      associated in 7 patients. RESULTS: There was one operative death. At discharge,
      echocardiographic morphofunctional assessment revealed: a reduction of the left
      ventricular end-diastolic and end-systolic volume indexes, an increase of the
      ejection fraction, and, most importantly, an improvement of remote myocardial
      shortening fraction. At a mean follow-up of 15.6 months (range 2-21 months),
      there were no late deaths and all survivors are in NYHA functional class I or II.
      CONCLUSIONS: Left ventricular restoration may represent an effective adjunct to
      the surgical management of patients with an acute extensive anterior myocardial
      infarction complicated by severe heart failure, with or without septal rupture.

PMID- 12784779
TI  - Relations between monophasic action potential duration and refractoriness after
      cardioversion of persistent atrial fibrillation: results in wash-out and
      amiodarone-treated patients.
AB  - BACKGROUND: The relation between repolarization and refractoriness has been
      clinically evaluated both in the atrium and ventricle. However, this relation has
      not been carefully investigated in the atria of patients with persistent atrial
      fibrillation after cardioversion. METHODS: We determined the refractoriness and
      monophasic action potential duration at 90% of repolarization (MAP90), at 5
      pacing cycle lengths (300 to 700 ms) and in 5 right atrial sites after internal
      cardioversion of persistent atrial fibrillation in 27 patients. RESULTS: The
      effective refractory periods (ERPs) were longer in amiodarone-treated patients
      (group 1) than in wash-out patients (group 2) (211.3 +/- 26.4 vs 199.1 +/- 24.3
      ms, p < 0.002) as well as the MAP90 (243.6 +/- 36.8 vs 223.1 +/- 29.2 ms, p <
      0.001). Linear regression analysis showed a direct relation between the MAP90 and
      ERP changes induced by different pacing cycle lengths (r = 0.77 and r = 0.92 in
      the amiodarone and wash-out patients, respectively). The ERP/MAP90 ratio was
      similar at all pacing cycle lengths in both wash-out and amiodarone groups and
      was always < 1. The mean ERP and MAP90 were shorter in the lateral right atrial
      sites than in the atrial roof and septum in both group 1 and group 2 patients (p
      < 0.001). CONCLUSIONS: A linear correlation was found between ERP and MAP90 in
      response to changes in pacing cycle lengths. Postrepolarization refractoriness
      was not observed after cardioversion of persistent atrial fibrillation.
      Pretreatment with oral amiodarone does not affect these electrophysiological
      features or the dispersion of ERP and MAP90 in the right atrium after sinus
      rhythm restoration.

PMID- 12784780
TI  - Therapeutic implications of contractile reserve elicited by dobutamine
      echocardiography in symptomatic, low-gradient aortic stenosis.
AB  - BACKGROUND: In patients with heart failure, poor ejection fraction and estimated
      severe aortic stenosis because of a reduced aortic valve area (AVA) and low
      gradients, dobutamine echocardiography (DE) was proposed to distinguish afterload
      mismatch from primary left ventricular dysfunction. In this setting the
      feasibility and safety of DE and the outcome following management based on DE
      results were investigated. METHODS: Forty-eight patients (mean age 73 +/- 9
      years; 79% males; AVA 0.7 +/- 0.2 cm2; mean aortic gradient 22 +/- 6 mmHg;
      ejection fraction 0.28 +/- 0.07; NYHA functional class 2.9 +/- 0.8) underwent DE
      and were followed up for 24 +/- 21 months. Aortic valve replacement (AVR) was
      offered to patients with left ventricular contractile reserve (ejection fraction
      increase > or = 30% at peak DE) and fixed aortic stenosis (AVA increase < or =
      0.25 cm2). RESULTS: DE elicited a left ventricular contractile reserve in 38
      patients (79%). Among these, fixed aortic stenosis was present in 28 patients,
      among whom 19 underwent AVR and 9 declined surgery. The 20 patients without
      contractile reserve or with relative stenosis (AVA increase > 0.25 cm2) were not
      considered eligible for surgery. During follow-up, 23 cardiovascular deaths
      occurred: 2/19 among operated patients, 7/9 among patients who declined surgery
      and 14/20 among non-eligible patients. Patients with AVR showed a significantly
      more favorable outcome and improved functional status as compared to the other
      two groups (NYHA class 1.2 +/- 0.4 vs 2.7 +/- 0.6 at baseline; p < 0.001).
      Conversely, non-surgical management was the strongest independent predictor of an
      adverse outcome (relative risk 3.6, 95% confidence interval 1.8-7.3; p < 0.0001).
      CONCLUSIONS: In patients with heart failure and estimated severe aortic stenosis,
      DE could identify a subgroup with a left ventricular contractile reserve and
      fixed aortic stenosis who gained great benefit from AVR. The clinical outcome of
      patients who were not operated upon was unfavorable.

PMID- 12784781
TI  - Stenting versus surgical bypass grafting for coronary artery disease: systematic
      overview and meta-analysis of randomized trials.
AB  - BACKGROUND: Coronary angioplasty and coronary artery bypass grafting (CABG) are
      both major techniques for the management of coronary artery disease, but CABG is
      associated with a lower incidence of repeat revascularization. Recent studies
      comparing angioplasty with stenting vs CABG have yielded conflicting results,
      with some suggesting improved survival with stenting, and others the opposite. We
      thus undertook a systematic overview of the randomized trials comparing stenting
      vs CABG in coronary artery disease. METHODS: MEDLINE (January 1986-February
      2003), ISI Current Contents, the Cochrane Controlled Trial Register, LILACS and
      the American Heart Association, American College of Cardiology, European Society
      of Cardiology, and Transcatheter Cardiovascular Therapeutics conference
      proceedings were among the databases we searched. Abstraction was performed in a
      non-blinded manner on pre-specified forms. The random-effect odds ratios for
      death, myocardial infarction, stroke, repeat revascularization, and symptomatic
      angina were computed for the longest available follow-up. RESULTS: Nine
      randomized trials (3283 patients, representing only 6% of all screened subjects)
      with an average follow-up of 28 months were included in the analysis, while four
      studies were excluded because they were still unpublished, ongoing, or with non
      systematic stenting. No study used drug-eluting stents. The odds ratios for
      stenting vs CABG were 0.82 (95% confidence interval-CI 0.57-1.18, p = 0.3) for
      the occurrence of death, non-fatal myocardial infarction or stroke, 4.6 (95% CI
      3.5-5.9, p < 0.00001) for repeat revascularization, and 2.3 (95% CI 1.8-2.8, p <
      0.00001) for symptomatic angina. Heterogeneity tests were not statistically
      significant. The results of sensitivity analysis were similar even after
      stratification for single vessel, off-pump, single center or high-quality
      studies. CONCLUSIONS: Overall and event-free survival after conventional stenting
      for coronary artery disease are similar to those after CABG, but surgery is still
      associated with a significantly lower incidence of repeat revascularization and
      symptoms. The role of next-generation drug-eluting stents in widening the
      indications for stenting and overcoming restenosis will need to be assessed in
      future observational and randomized studies comparing stenting vs CABG.

PMID- 12784782
TI  - Acute coronary syndrome and late stent failure in a patient with Behcet's
      syndrome.
AB  - The present case report describes the occurrence of an acute coronary syndrome
      and of a post-percutaneous coronary intervention complication in a patient with
      Behcet's syndrome. An active phase of this syndrome, through an increased
      oxidative stress and reduced nitric oxide availability, could explain both an
      early myocardial infarction as well as an infarction following late in-stent
      reocclusion. This complication can be very difficult to treat.

PMID- 12784784
TI  - Three-dimensional volume rendering with multislice computed tomography in the
      evaluation of Aortic coarctation.

PMID- 12784783
TI  - Images in cardiovascular medicine. Transcatheter balloon recanalization of an
      occluded modified Blalock-Taussig shunt.

PMID- 12784786
TI  - Reviewing professional boundaries in the NHS.

PMID- 12784785
TI  - Trusts ignore growing mental health needs.

PMID- 12784787
TI  - Urinary catheters: selection, management and prevention of infection.
AB  - Urinary catheterization is a common procedure for both hospital and community
      patients. Nurses make many of the decisions in regard to both catheter selection
      and subsequent catheter care. These decisions, for example, in the type of
      catheterization (intermittent, indwelling, urethral or suprapubic) should be made
      on an informed basis. Choosing the optimum catheter material and size can benefit
      catheter care. Encrustation can be a problem for some catheterized patients and
      nurses are often involved in trying to prevent or treat it. This and other
      aspects of catheter management including infection control, constipation and
      meatal hygiene are discussed.

PMID- 12784788
TI  - The district nurse's role as patient advocate: case study.
AB  - Controversy exists regarding whether or not nurses should act act as patient
      advocates. This article describes a case study in which a district nurse (DN)
      acted as an advocate for a patient, who was removed from his GP's register. A
      structured approach using six stages of advocacy (Bateman, 1995) is applied to
      this case scenario. Legal, ethical and professional issues are explored to
      determine the DN's position in advocacy. By acting as patient advocate the DN
      enhanced the therapeutic relationship with the patient and improved his access to
      health care. Although the extent to which a DN can act as advocate is somewhat
      limited, advocacy positively complimented and contributed to the role of the DN
      in this case study.

PMID- 12784789
TI  - The management of schizophrenia: cognitive behavioural therapy.
AB  - Over the past decade advances in the management of schizophrenia in the community
      have involved increasing emphasis on the psychosocial dynamics of care,
      coordinated through a care programme approach, and the introduction of new
      medication. In particular, the use of cognitive behavioural therapy (CBT) has
      been shown to be an effective means of tackling symptoms associated with
      schizophrenia (Jones et al, 1998). While some of the techniques used in CBT may
      be too advanced for untrained therapists to use, the approach described in this
      article may be used by registered mental health nurses and community
      professionals. This approach includes medication adherence, coping strategies,
      questioning style, the prevention of patient relapse and dealing with relatives.

PMID- 12784790
TI  - Using EMDR to treat post-traumatic stress disorder in a prison setting.
AB  - This article describes the treatment of a young man who developed post-traumatic
      stress disorder (PTSD) following the sudden unexpected miscarriage of his unborn
      child. He was diagnosed with this anxiety disorder while serving a term of
      imprisonment. He was treated with a controversial psychological treatment for
      PTSD, eye movement desensitisation reprocessing (EMDR) therapy, during one, 1
      hour session. After this session, his progress was monitored by a further three
      follow-up appointments at 1 week, 1 month and 3 months, where the self-report
      questionnaires were repeated and compared with pre-treatment scores. These
      demonstrated improvement post-treatment and at a 3-month follow-up session. The
      discussion arising from the treatment will concentrate on EMDR as an effective
      treatment for PTSD, particularly within a prison setting. Data from recent
      research highlight the potential risks of PTSD within a community population and
      the implications for midwives and nurses who treat and care for traumatized
      patients are discussed.

PMID- 12784791
TI  - Legal issues arising in community nursing. 3: Consent and compulsion.

PMID- 12784792
TI  - Self-inflicted wounding. 2: Identification, assessment and management.
AB  - The spectrum of conditions associated with self-inflicted wounding and their
      presenting features were outlined in the first part of this article (Moffatt,
      1999). In part two, the assessment and management of self-wounding patients is
      discussed. Manipulative behaviour can be a barrier to treatment, as well as a
      disruptive force within the healthcare team. Awareness of its effects are
      essential to the successful development of a therapeutic relationship. However,
      the current possibilities for effective treatment of self-wounding are limited,
      and there is an urgent need for more research into both its causes and the
      various management options available.

PMID- 12784794
TI  - Obesity: a challenge for community nurses.

PMID- 12784793
TI  - The effectiveness of preschool vision screening by health visitors.
AB  - The aim of this study was to determine the effectiveness of preschool vision
      surveillance by health visitors in Warrington, a district with a secondary
      community orthoptic service. Of the 2041 children screened by health visitors at
      3-3 1/2 years 12% were referred to the orthoptist for further assessment. Sixty
      three per cent of these required more than one examination by the orthoptist and
      28% were subsequently referred to an ophthalmologist for further assessment.
      Amblyopia was detected in 11 children, 5 had squints without amblyopia, and in
      addition 25 children had significant refractive errors. A retrospective review of
      the records of children identified with amblyopia following a school entry
      medical at 5 years was undertaken to detect possible failure of the earlier
      health visitor examination (i.e. false negatives at age 3-3 1/2 years). Possible
      failure of early screening was found in only two children, one of whom had a
      minor defect only (6/9). Vision screening for children aged 3-3 1/2 years by
      health visitors is an effective alternative to primary screening by orthoptists.
      However, the use of health visitors in this role is contrary to current national
      guidelines. The findings suggest that using health visitors to screen vision in
      preschool children makes efficient use of existing routine checks and may be the
      best use of orthoptic time.

PMID- 12784795
TI  - Pyoderma gangrenosum of the skin and respiratory tract in a 5-year-old girl.

PMID- 12784796
TI  - Surgery in gynecologic oncology--yesterday, today and tomorrow. Presented to the
      German Society of Gynecology and Obstetrics Dusseldorf, September 2002.

PMID- 12784797
TI  - Circular excision of hemangioma and purse-string closure: the smallest possible
      scar.

PMID- 12784798
TI  - [New understanding about plasticity of adult stem cells and its implications in
      the regenerative medicine].

PMID- 12784799
TI  - ["Transdifferentiation" or "plasticity" of adult stem cells was called vitally in
      question--reveal the biological property of adult stem cells in its true colors].

PMID- 12784800
TI  - [Natural history and prognosis of pulmonary embolism].

PMID- 12784801
TI  - [New research on anti-tuberculosis vaccines].

PMID- 12784802
TI  - The virtual graduate program in bioethics: the mission, the students, and the
      hazards.

PMID- 12784803
TI  - Why an online graduate bioethics program: one student's experience.

PMID- 12784804
TI  - Bioethics, medical humanities, and the future of the "field": Reflections on the
      results of the ASBH survey of North American graduate bioethics/medical
      humanities training programs.

PMID- 12784806
TI  - Towards individualized health management: the importance of bio-medical
      information sciences.

PMID- 12784805
TI  - Evaluating graduate programs in bioethics: what measures should we use?

PMID- 12784807
TI  - Epididymo-orchitis complicating Streptococcus pyogenes throat infection.

PMID- 12784808
TI  - Injury caused by baby walkers.

PMID- 12784809
TI  - Injury caused by baby walkers.

PMID- 12784810
TI  - Medical Professionalism Project.

PMID- 12784811
TI  - Medical Professionalism Project.

PMID- 12784812
TI  - IRBs and continuing review: regulatory interference or vital safeguard?

PMID- 12784813
TI  - Evaluating IRBs and their roles.

PMID- 12784814
TI  - Twerski and Cohen's second revolution: a systems/strategic perspective.

PMID- 12784815
TI  - Regulating scientific research: intellectual property rights and the norms of
      science.

PMID- 12784816
TI  - Prenatal testing: the perceptions and experiences of Muslim women in Australia.
AB  - This paper examines how Muslim women perceive and experience prenatal testing. In
      addition, we look at women's partners and their opinions relating to prenatal
      testing. The paper is based on in-depth interviews with immigrant women who
      identify themselves as followers of Islam and are now living in Australia. The
      women have, in general, positive attitudes toward prenatal testing, particularly
      ultrasound. However, some are ambivalent about amniocentesis. Despite their
      doubts, women tend to accept prenatal testing as they believe it is routine in
      antenatal care and confirms their own perceptions of being a 'normal mother', who
      should accept advice from their doctors. Women's partners also play an important
      role in the acceptance of prenatal testing among women in this study. We argue
      that women's perceptions and subjective experience of prenatal testing should be
      taken into account when providing prenatal services to them. Women need to be
      given a choice rather than being pressured and made to conform to the
      routinization of prenatal testing which as taken place in the Australian health
      care system. Only then will we see sensitive health care provided for women in
      general and for Muslim immigrant women in particular.

PMID- 12784819
TI  - Study reaffirms autopsy's value but not a specific role in measuring performance.

PMID- 12784818
TI  - Unusual problems in breast cancer and a rare lung cancer case. Case 3.
      Simultaneous and synchronous bilateral inflammatory breast cancer.

PMID- 12784817
TI  - The making of a memory mechanism.
AB  - Long-Term Publication (LTP) is a kind of synaptic plasticity that many
      contemporary neuroscientists believe is a component in mechanisms of memory. This
      essay describes the discovery of LTP and the development of the LTP research
      program. The story begins in the 1950's with the discovery of synaptic plasticity
      in the hippocampus (a medial temporal lobe structure now associated with memory),
      and it ends in 1973 with the publication of three papers sketching the future
      course of the LTP research program. The making of LTP was a protracted affair.
      Hippocampal synaptic plasticity was initially encountered as an experimental
      tool, then reported as a curiosity, and finally included in the ontic store of
      the neurosciences. Early researchers were not investigating the hippocampus in
      search of a memory mechanism; rather, they saw the hippocampus as a useful
      experimental model or as a structure implicated in the etiology of epilepsy. The
      link between hippocampal synaptic plasticity and learning or memory was a
      separate conceptual achievement. That link was formulated in at least three
      different ways at different times: reductively (claiming that plasticity is
      identical to learning), analogically (claiming that plasticity is an example or
      model of learning(, and mechanistically (claiming that plasticity is a component
      in learning or memory mechanisms). The hypothesized link with learning or memory,
      coupled with developments in experimental techniques and preparations, shaped how
      researchers understood LTP itself. By 1973, the mechanistic formulation of the
      link between LTP and memory provided an abstract framework around which findings
      from multiple perspectives could be integrated into a multifield research
      program.

PMID- 12784820
TI  - Primary PCI for ST-segment elevation myocardial infarction in a patient treated
      with subcutaneous enoxaparin utilizing point-of-care Enox test.
AB  - The superiority of enoxaparin compared with unfractionated heparin in the medical
      management of patients with non-ST elevation acute coronary syndromes (NSTE ACS)
      has been demonstrated in clinical trials. Further, enoxaparin has been shown to
      be safe and effective during PCI, including in combination with glycoprotein
      IIb/IIIa inhibitors. Whether enoxaparin is superior to unfractionated heparin in
      patients with NSTE ACS under-going early invasive strategy is currently being
      tested in a large clinical trial. Data on the use of enoxaparin in patients
      undergoing primary angioplasty for ST-segment elevation myocardial infarction are
      limited. Unlike patients who present to the catheterization laboratory after
      several doses of enoxaparin where in a steady state anticoagulation might have
      been achieved, patients who present early after administration of a single dose
      of subcutaneous enoxaparin may not have an adequate level of anticoagulation for
      PCI. The ability to monitor activity of enoxaparin in such patients using a point
      of-care test might be useful. This report describes a patient with ST-segment
      elevation myocardial infarction who presented for primary angioplasty 75 minutes
      after administration of subcutaneous enoxaparin. The Rapidpoint Enox test
      measured 135 seconds and the patient's corresponding serum anti-Xa level was 0.12
      IU/mL indicating a suboptimal level of anticoagulation for PCI. Procedural
      success was attained using additional 0.3-mg/kg intravenous enoxaparin.

PMID- 12784821
TI  - Medicare quality improves but could be better, study says.

PMID- 12784822
TI  - Heated chemotherapy improves survival and quality of life in peritoneal
      carcinomatosis patients.

PMID- 12784823
TI  - Study outlines relationship between racial/ethnic differences and breast cancer
      outcomes.

PMID- 12784824
TI  - Abstracts of the 8th Liposome Research Days Conference. Berlin-Buch, Germany. May
      21-24, 2002.

PMID- 12784825
TI  - Orthopedic devices; classification for the resorbable calcium salt bone void
      filler device. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the resorbable calcium salt
      bone void filler device intended to fill bony voids or gaps of the extremities,
      spine, and pelvis that are caused by trauma or surgery and are not intrinsic to
      the stability of the bony structure into class II (special controls). Elsewhere
      in this issue of the Federal Register, FDA is announcing the availability of a
      class II special controls guidance entitled "Class II Special Controls Guidance
      Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry
      and FDA." This action is being undertaken based on new information submitted in a
      classification proposal from Wright Medical Technology under the Federal Food,
      Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the
      Safe Medical Devices Act of 1990, and the Food and Drug Administration
      Modernization Act of 1997.

PMID- 12784826
TI  - Medical devices; designation of special control for eight surgical suture
      devices. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to amend the
      classification regulations for eight surgical suture devices previously
      reclassified into class II to specify a special control for those devices. The
      special control is an FDA guidance document entitled "Class II Special Controls
      Guidance Document: Surgical Sutures; Guidance for Industry and FDA" that
      identifies performance, testing, and labeling recommendations for the devices.
      Elsewhere in this issue of the Federal Register, FDA is announcing the
      availability of the guidance document that will serve as the special control. FDA
      is taking these actions on its own initiative because it believes they are
      necessary to provide reasonable assurance of the safety and effectiveness of
      surgical suture devices. These actions are being taken under the Federal Food,
      Drug, and Cosmetic Act (the act).

PMID- 12784827
TI  - The normative development of child and adolescent problem behavior.
AB  - The aim of this study was to identify normative developmental trajectories of
      parent-reported problems assessed with the Child Behavior Checklist (CBCL; T. M.
      Achenbach, 1991) in a representative sample of 2,076 children aged 4 to 18 years
      from the general population. The trajectories were determined by multilevel
      growth curve analyses on the CBCL syndromes in a Longitudinal multiple birth
      cohort sample that was assessed 5 times with 2-year intervals. Most syndromes
      showed a linear increase or decrease with age or a curvilinear trajectory, except
      for thought problems. Trajectories for most syndromes differed for boys versus
      girls, except those for withdrawn, social problems, and thought problems. These
      normative developmental trajectories provide information against which
      developmental deviance in childhood and adolescence can be detected.

PMID- 12784828
TI  - Borderline personality disorder from the perspective of general personality
      functioning.
AB  - The authors extended previous work on the hypothesis that borderline personality
      disorder (BPD) can be understood as a maladaptive variant of personality traits
      included within the 5-factor model (FFM) of personality. In each of 3 samples, an
      empirically derived prototypic FFM borderline profile was correlated with
      individuals' FFM profiles to yield a similarity score, an FFM borderline index.
      Results across all samples indicated that the FFM borderline index correlated as
      highly with existing borderline measures as they correlated with one another, and
      the FFM borderline index correlated as highly with measures of dysfunction,
      history of childhood abuse, and parental psychopathology as did traditional
      measures of BPD. Findings support the hypothesis that BPD is a maladaptive
      variant of FFM personality traits.

PMID- 12784829
TI  - Effects of daily events on mood states in major depressive disorder.
AB  - Major depressive disorder (MDD) is characterized by high negative affect (NA) and
      low positive affect (PA), but little is known about emotional reactivity in daily
      life. The authors used experience sampling methodology to investigate changes in
      NA and PA following minor daily events in MDD compared with healthy participants.
      Contrary to expectation, MDD participants did not report more frequent negative
      events, although they did report fewer positive events. Multilevel regression
      showed that both NA and PA responses to negative events were blunted in the MDD
      group, whereas responses to positive events were enhanced. NA responses to
      negative events persisted longer in MDD participants. Depressed participants with
      a positive family history or longer current episodes showed relatively greater NA
      responses to negative events.

PMID- 12784830
TI  - Contrasting two accounts of anxiety-linked attentional bias: selective attention
      to varying levels of stimulus threat intensity.
AB  - Previous research has established that clinical anxiety patients and nonclinical
      populations with high levels of anxiety vulnerability characteristically orient
      attention toward moderately threatening stimuli. In contrast, populations with
      low levels of anxiety vulnerability typically orient attention away from such
      stimuli. The differing experimental predictions generated by 2 classes of
      hypothetical explanation for this anxiety-linked attentional discrepancy were
      tested, using attentional probe methodology to compare the attentional responses
      of high and low trait anxious individuals to facial stimuli of differing threat
      intensities. The results support the view that all individuals orient attention
      away from mildly threatening stimuli and toward strongly threatening stimuli,
      with differences in anxiety vulnerability reflecting the intensity of stimulus
      threat required to elicit the attentional vigilance response.

PMID- 12784831
TI  - Relapse as a nonlinear dynamic system: application to patients with alcohol use
      disorders.
AB  - Understanding the relapse process is one of the most important issues in
      addictive behaviors research. To date, most studies have taken a linear approach
      toward predicting relapse based on risk factors. Nonlinear dynamical systems
      theory can be used to describe processes that are not adequately modeled using a
      linear approach. In particular, the authors propose that catastrophe theory, a
      subset of nonlinear dynamical systems theory, can be used to describe the relapse
      process in addictive behaviors. Two small prospective studies using 6-month
      follow-ups of patients with alcohol use disorders (inpatient, n = 51; outpatient,
      n = 43) illustrate how cusp catastrophe theory may be used to predict relapse.
      Results from these preliminary studies indicate that a cusp catastrophe model has
      more predictive utility than traditional linear models.

PMID- 12784832
TI  - Is depression taxonic, dimensional, or both?
AB  - The current investigation examines the potential importance of item selection in
      the ongoing discussion regarding the taxonicity of depression. Following J. C.
      Coyne (1994), we contrast the taxonicity of "distress" with the taxonicity of a
      syndrome more focused on somatic symptoms (i.e., the involuntary defeat
      syndrome). Using 4 samples of 984 undergraduates, we first replicate the J.
      Ruscio and A. M. Ruscio (2000) results by showing that distress item indicators
      are dimensional. We then demonstrate taxonicity using items focused on somatic
      symptoms and reflective of disruption of multiple homeostatic mechanisms. Results
      suggest that item selection is central to the determination of taxonicity in
      depression.

PMID- 12784833
TI  - Directed forgetting between, but not within, dissociative personality states.
AB  - To investigate amnesia between identities in dissociative identity disorder
      (DID), the authors assessed explicit and implicit memory performance on a
      directed-forgetting task in 12 DID patients who switched from one state to an
      "amnesic" state between presentation and memory testing. DID patients were
      instructed either to remember or to forget neutral and emotional words. Besides
      an overall decrease in explicit memory, patients demonstrated selective
      forgetting of to-be-forgotten, but not of to-be-remembered words in the amnesic
      state. Patients did not exhibit any directed forgetting within the same state.
      Implicit memory was fully preserved across states. Independent of state, patients
      recalled more emotional than neutral information. These results may extend the
      conceptualization of memory processes in DID, suggesting an important role for
      retrieval inhibition.

PMID- 12784834
TI  - The symptomatic expression of major depressive disorder in adolescents and young
      adults.
AB  - Data from the Oregon Adolescent Depression Project were used to examine the
      symptomatic expression of major depressive disorder (MDD) as a function of age
      and gender. The objective was to investigate the phenomenological nature of MDD
      among a cohort of adolescents as they progressed into early adulthood. The
      analyses were based on 564 participants who had experienced MDD in their
      lifetime. No systematic differences in the relative rate of occurrence of
      specific symptoms across episodes and only minor symptom differences between male
      and female participants were found. Age did not significantly influence the
      symptom picture. Stability of specific symptoms and episode severity across
      episodes was low. The results are discussed within the context of a stressor
      symptom matching model.

PMID- 12784835
TI  - Do age of onset and course of illness define biologically distinct groups within
      atypical depression?
AB  - Illness course separates patients with atypical depression into tricyclic
      responders and nonresponders as does perceptual asymmetry. The authors therefore
      investigated whether the course-of-illness parameters would define groups within
      atypical depression differing in brain laterality. Patients with atypical
      depression were assessed for illness course and brain laterality. Two patient
      groups were defined, 1 with onset prior to age 20 plus a very chronic course, and
      a 2nd group having later onset or less chronic illness. Patients reporting early
      onset of very chronic dysphoria showed significantly less right-ear (left
      hemisphere) accuracy and also differed in characteristic perceptual asymmetry
      when compared to patients with later onset or less chronicity. Course of illness
      may usefully define more homogeneous depressive subgroups within atypical
      depression.

PMID- 12784836
TI  - The natural history of problem gambling from age 18 to 29.
AB  - Aggregate-level prevalences and individual-level developmental trajectories of
      untreated problem gambling were examined in an 11-year, 4-wave longitudinal study
      spanning the adolescent through young adult years. The past-year prevalences, 3-4
      year incidences, and lifetime prevalences of problem gambling from adolescence
      through young adulthood were relatively stable at 2%-3%, 1%-2%, and 3%-5%,
      respectively. Despite the stability of the prevalences at the aggregate level,
      problem gambling appeared to be more transitory and episodic than enduring and
      chronic at the individual level. The present study is consistent with the limited
      evidence available on the natural history of problem gambling in the community in
      suggesting that natural recovery may be the rule rather than the exception.

PMID- 12784837
TI  - The moderating effects of dispositional empathy on alcohol-related aggression in
      men and women.
AB  - The author investigated the influence of dispositional empathy on alcohol-related
      aggression in men and women. Participants were 204 (111 men, 93 women) healthy
      social drinkers, 21-35 years old. Dispositional empathy was measured with the
      Interpersonal Reactivity Index. Following the consumption of either an alcoholic
      or a placebo beverage, participants were tested on a modified version of the
      Taylor Aggression Paradigm in which mild electric shocks were received from, and
      administered to, a fictitious opponent during a competitive task. Alcohol
      increased aggression for persons (particularly men) with lower, as opposed to
      higher, levels of empathy. Men with lower empathy levels exhibited the most
      aggression followed by men with higher empathy levels. Women displayed the least
      aggression regardless of their empathy levels.

PMID- 12784839
TI  - Interidentity amnesia for neutral, episodic information in dissociative identity
      disorder.
AB  - Interidentity amnesia is considered a hallmark of dissociative identity disorder
      (DID) in clinical practice. In this study, objective methods of testing episodic
      memory transfer between identities were used. Tests of both recall (interference
      paradigm) and recognition were used. A sample of 31 DID patients was included.
      Additionally, 50 control subjects participated, half functioning as normal
      controls and the other half simulating interidentity amnesia. Twenty-one patients
      subjectively reported complete one-way amnesia for the learning episode. However,
      objectively, neither recall nor recognition scores of patients were different
      from those of normal controls. It is suggested that clinical models of amnesia in
      DID may be specified to exclude episodic memory impairments for emotionally
      neutral material.

PMID- 12784838
TI  - Genetic influences on the association between personality risk factors and
      alcohol use and abuse.
AB  - The authors assessed the association of 2 personality dimensions with use and
      abuse of alcohol in 1,320 twin pairs concordantly reporting nonabstinence at age
      18.5 years. The 2 alcohol outcomes differentially relate to the 2 personality
      dimensions: Alcohol-related problems correlate more highly with social deviance
      than with excitement seeking (ES), and alcohol consumption correlates more highly
      with ES than with social deviance. Biometric models fit to the data identified
      similar patterns in genetic covariance, although differences were more evident in
      genetic correlations between social deviance and alcohol outcomes than in those
      for ES. Results suggest that genetic influences underlie the association of
      personality with alcohol use and subsequent problems and illustrate the utility
      of informative twin analyses in exploring links between genes, personality, and
      behavior disorder.

PMID- 12784840
TI  - Investigating the construct validity of the dissociative taxon: stability
      analyses of normal and pathological dissociation.
AB  - Research has suggested the existence of a pathological dissociative taxon.
      However, relatively little is known about this taxon. This study examined the 2
      month retest stability of this taxon--together with other measures of
      dissociation and the Big Five--in a sample of 465 undergraduates. Contrary to
      expectation, taxon scores were only modestly stable and were substantially less
      stable than the other measures, including continuous indicators of dissociation.
      Furthermore, most individuals who were identified as taxon members at one
      assessment were classified as nonmembers at the other. These results challenge
      the existence of a pathological dissociative taxon. More generally, these data
      demonstrate that statistically identified taxa need to be explicated through the
      normal process of construct validation.

PMID- 12784841
TI  - Alcohol intoxication and self-aggressive behavior.
AB  - Nonexperimental field studies have demonstrated an association between alcohol
      intoxication and self-aggressive behaviors across the spectrum of lethality.
      Although these results are suggestive, it is not yet known whether alcohol
      intoxication is causally related to self-aggression. The authors therefore
      experimentally examined the effects of alcohol intoxication (mean blood alcohol
      concentration of .10) on a behavioral measure of self-aggression in men (N = 40).
      After consuming either an alcohol or a placebo drink, participants were provided
      the opportunity to self-administer shock during a task disguised as a reaction
      time game, with self-aggression defined by the intensity of shock chosen. Half of
      the participants observed a self-aggressive model (a potential moderator of
      alcohol-related self-aggression). Independent alcohol and model effects were
      found, with alcohol accounting for over 30% of the self-aggression variance.

PMID- 12784842
TI  - Whither clinical investigation?

PMID- 12784843
TI  - Evolution: not essential for modern medicine.

PMID- 12784844
TI  - Comment on "Barrier facilities for transgenic rodents in academic centers--a two
      edged sword".

PMID- 12784845
TI  - Mouse nomenclature and maintenance of genetically engineered mice.
AB  - Modern genetic engineering technologies enable us to manipulate the mouse genome
      in increasingly complex ways to model human biology and disease. As a result, the
      number of mouse strains carrying transgenes or induced mutations has increased
      markedly. Thorough understanding of strain and gene nomenclature is essential to
      ensure that investigators know what kind of mouse they have, and what to expect
      in terms of phenotype. Genetically engineered mice alter gene function by over
      expressing, eliminating, or modifying a gene product. The resulting phenotype is
      often unexpected and not completely understood, necessitating special care and
      potentially complex breeding and husbandry strategies. Animal care technicians
      responsible for routine maintenance of the colony, facility managers,
      veterinarians, and research personnel working with mice should be well informed
      about the nature of the mutation, distinguishing characteristics, and necessary
      precautions in handling the mice. Personnel working with mice also must be aware
      of the multitude of factors intrinsic to the mouse and present in the environment
      that can influence reproductive performance. Finally, diligent adherence to the
      maintenance of genetic quality in conjunction with cryopreservation of germplasm
      is the best insurance against loss of a colony.

PMID- 12784846
TI  - Transgenic animal technology: alternatives in genotyping and phenotyping.
AB  - Over the past decade, breakthrough technologies in transgenic animal technology
      and functional genomics have played a central role in the explosive growth of
      rodent modeling and in scientific innovation. Various noninvasive alternatives to
      routine surgical biopsy have been described for genotypic and phenotypic analyses
      of laboratory animals. A number of options are available to refine or replace
      potentially painful and invasive procedures ranging from tissue biopsies
      (including tail biopsies and toe docking) to several blood sampling techniques.
      Unfortunately, adoption of many non- or minimally invasive alternatives has
      proven difficult on a number of fronts ranging from historical reservations to
      procedural expectations and actual experimental productivity. Similarly, a
      variety of phenotyping considerations have addressed throughput efficiencies and
      the health and well being of research animals. From an animal welfare
      perspective, marked increases in laboratory animal populations have accompanied
      rapid advancements spanning the life sciences. As described for rodent modeling,
      but with applications across many laboratory animal species, diverse procedural
      refinements are available that will readily aid in the analysis of whole animal
      models. Ultimately, non-invasive technologies and complementary refinements have
      bearing on the quality and reproducibility of data that are reported, as well as
      of critical importance to the well being and ethical management of animals at all
      developmental stages: from fetal existence, to the neonatal period, and on
      through adulthood.

PMID- 12784847
TI  - Behavioral phenotyping of rodents.
AB  - Established methods for analyzing behavioral traits in mutant lines of mice allow
      researchers to understand the outcomes of genetic manipulations in the nervous
      system. A rigorous six-tiered behavioral phenotyping strategy is described.
      Recommendations are offered for the design of mouse behavioral testing suites in
      animal housing facilities.

PMID- 12784848
TI  - Components of gene therapy experimentation that contribute to relative risk.
AB  - Gene therapy is the purposeful delivery of genetic material to somatic cells for
      the purpose of treating disease or biomedical investigation. Either viral or non
      viral vector methods can be used. The risk of collateral exposure of laboratory
      animal care personnel to gene therapy vectors is dependent on a number of
      factors. These factors are intrinsic to the gene therapy vector (the vehicle for
      genetic conveyance), product encoded by the genetic construct delivered, method
      of delivery, and immune status of the recipient. The component risks of gene
      therapy experiments can be analyzed to surmise the overall relative risk of the
      experiment. Knowledge of the components that contribute potential hazardous risk
      to a study can assist animal care staff in identifying area(s) where prudent
      practices should be focused. Gene therapy experiments involving viral vectors are
      generally performed at either biosafety level 2 or 3. The objective of this
      review is to report on various components of gene therapy experiments, focusing
      on characteristics of viral and non-viral vectors, to assist the laboratory
      animal science community in determining prudent biosafety practices.

PMID- 12784849
TI  - The National Institutes of Health system for enhancing the science, safety, and
      ethics of recombinant DNA research.
AB  - Oversight of recombinant DNA research by the National Institutes of Health (NIH)
      is predicated on ethical and scientific responsibilities that are akin, in many
      ways, to those that pertain to the oversight of animal research. The NIH system
      of oversight, which originated more than 25 years ago, is managed by the NIH
      Office of Biotechnology Activities (OBA), which uses various tools to fulfill its
      oversight responsibilities. These tools include the NIH Guidelines for Research
      Involving Recombinant DNA Molecules (NIH Guidelines) and the Recombinant DNA
      Advisory Committee. The OBA also undertakes special initiatives to promote the
      analysis and dissemination of information key to our understanding of recombinant
      DNA, and in particular, human gene transfer research. These initiatives include a
      new query-capable database, an analytical board of scientific and medical
      experts, and conferences and symposia on timely scientific, safety, and policy
      issues. Veterinary scientists can play an important role in the oversight of
      recombinant DNA research and in enhancing our understanding of the many safety
      and scientific dimensions of the field. These roles include developing
      appropriate animal models, reporting key safety data, enhancing institutional
      biosafety review, and promoting compliance with the NIH Guidelines.

PMID- 12784850
TI  - Antigen recognition by serum antibodies in non-human primates experimentally
      infected with Mycobacterium tuberculosis.
AB  - Tuberculosis is a significant threat to non-human primates and their caretakers.
      The diagnosis of tuberculosis in living non-human primates is currently based on
      the tuberculin skin test, which is cumbersome and sometimes inaccurate.
      Development of an accurate serodiagnostic test requires identification of the key
      antigens of Mycobacterium tuberculosis involved in antibody production. When
      sequential serum samples obtained from 17 cynomolgus, rhesus, and African green
      monkeys up to seven months since experimental infection with M. tuberculosis
      Erdman were screened for antibody against purified proteins of M. tuberculosis,
      three highly seroreactive antigens were identified. One protein, ESAT-6, reacted
      with sera from all infected animals. Two additional proteins, alpha-crystallin
      and MTSA-10, were recognized by sera from approximately 90% of infected animals.
      Time course analysis of antibody production indicated that the earliest response
      was usually to ESAT-6 alone or to ESAT-6 and other antigen(s). These results
      provide experimental evidence of the potential value of ESAT-6 as an antigen for
      use in serodiagnosis of tuberculosis in non-human primates.

PMID- 12784851
TI  - Detection of sendai virus and pneumonia virus of mice by use of fluorogenic
      nuclease reverse transcriptase polymerase chain reaction analysis.
AB  - Sendai virus may induce acute respiratory tract disease in laboratory mice and is
      a common contaminant of biological materials. Pneumonia virus of mice (PVM) also
      infects the respiratory tract and, like Sendai virus, may induce a persistent
      wasting disease syndrome in immunodeficient mice. Reverse transcriptase
      polymerase chain reaction (RT-PCR) assays have proven useful for detection of
      Sendai virus and PVM immunodeficient animals and contaminated biomaterials.
      Fluorogenic nuclease RT-PCR assays (fnRT-PCR) combine RT-PCR with an internal
      fluorogenic hybridization probe, thereby potentially enhancing specificity and
      eliminating post-PCR processing. Therefore, fnRT-PCR assays specific for Sendai
      virus and PVM were developed by targeting primer andprobe sequences to unique
      regions of the Sendai virus nucleocapsid (NP) gene and the PVM attachment (G)
      gene, respectively. The Sendai virus and PVM fnRT-PCR assays detected only Sendai
      virusand PVM , respectively. Neither assay detected other viruses of the family
      Paramyxoviridae or other RNA viruses that naturally infect rodents. The fnRT-PCR
      assays detected as little as 10 fg of Sendai virus RNA and one picogram of PVM
      RNA, respectively, andthe Sendai virus fnRT-PCR assay had comparable sensitivity
      when directly compared with the mouse antibody production test. The fnRT-PCR
      assays were also able to detect viral RNA in respiratory tract tissues and cage
      swipe specimens collected from experimentally inoculated C.B-17 severe combined
      immunodeficient mice, but did not detect viral RNA in age- and strain-matched
      mock-infected mice. In conclusion, these fnRT-PCR assays offer potentially high
      throughput diagnostic assays to detect Sendai virus and PVM in immunodeficient
      mice, and to detect Sendai virus in contaminated biological materials.

PMID- 12784852
TI  - Hemodynamic indices versus gastric tonometric measurements for prognosis of
      hemorrhagic shock: a porcine model.
AB  - The aim of the study reported here was to assess the prognostic value of gastric
      tonometry and its implications in the initial phases of hemorrhagic shock.
      Hemorrhagic shock was induced by use of femoral arterial bleeding in 12 hybrid
      swine under general anesthesia. Approximately 30% of the circulating blood volume
      was removed, until mean arterial pressure of 45 mmHg was reached. The shock
      conditions were observed over a limited period (90 min) by comparing traditional
      hemodynamic parameters with gastric tonometric measurements and tissue
      oxygenation. After a shock period of 90 min without pharmacologic treatment,
      blood was collected in acid-citrate dextrose-treated bags and was reinfused via
      the right femoral vein. At the end of the experiment, seven animals had good
      hemodynamic recovery on reinfusion (group A), whereas values in five animals
      deceased in the same phase (group B). Hemodynamic and gastric tonometric results
      were compared between survivors and nonsurvivors. Intravascular volume
      restoration and reduction of systemic vascular resistance (SVR) enabled the
      animals of group A to maintain standard ventricular kinetics and recover in terms
      of splanchnic regional flow. In addition, increase in intramucosal gastric pH
      (pHi), decrease in the pH-gap (pHa-Hi), and progressive restoration in gastric
      wall tissue oxygenation (PtO2) also were observed. These results suggest that
      useful diagnostic and therapeutic indications can be obtained by acquisition of
      simple hemodynamic measurements at the beginning of the shock period. On the
      basis of results of statistical analysis, only mean arterial pressure and SVR
      were good indicators of shock development, whereas pHi was not a significant
      factor in this experimental model.

PMID- 12784854
TI  - Genetic analysis of a Theiler-like virus isolated from rats.
AB  - Although cardioviruses related to Theiler's murine encephalomyelitis virus (TMEV)
      appear to be common in mice and rats, few TMEV isolates have been obtained from
      rat colonies. In 1991, a cardiovirus isolate designated NGS910 was obtained from
      sentinel rats exposed to cage bedding previously used by adult rats that were
      TMEV seropositive, but had never manifested clinical signs of disease. To
      determine to which group and subgroup of cardiovirus this virus belongs, the
      sequence of the viral genome was determined. The NGS910 genome consisted of 8,021
      nucleotides and the 5'-nontranslated region had a predicted secondary structure
      that is similar to members of the TMEV group of cardioviruses. The Leader-P3D
      open reading frame (L ORF) of NGS910 had strong homology with L ORFs of other
      TMEVs (72% identity), but lower homology with EMCV cardioviruses (55 to 56%).
      Phylogenetic analyses on the basis of aligned nucleotide sequences of the L ORF
      (6,924 b) and the internal L* ORF (471 b) supported this classification of NGS910
      as a TMEV strain. However, within the TMEV group, NGS910 wassufficiently
      divergent from other isolates that it could not be regarded as simply a mutant
      strain of a known TMEV. As genetic distances between NGS910 and other TMEVs were
      greater than those between Mengo virus of EMCV and other EMCVs, we propose to
      designate the NGS910 isolate as a rat Theiler-like virus.

PMID- 12784853
TI  - Physiologic melatonin concentration, omega-3 fatty acids, and conjugated linoleic
      acid inhibit fatty acid transport in rodent hind limb skeletal muscle in vivo.
AB  - Melatonin (MLT), the circadian neurohormone secreted by the pineal gland in
      mammals during darkness, eicosapentanoic acid (EPA), and conjugated linoleic acid
      (CLA) have established regulatory roles in cancer growth. Investigations in our
      laboratory have indicated that these agents inhibit fatty acid (FA) transport by
      tumors and several sub-types of white adipose tissue via inhibitory G protein
      coupled receptor mechanisms. Skeletal muscle constitutes over 45% of human body
      mass and plays an important role in cancer cachexia and obesity-related diseases.
      Since fatty acid oxidation is a major source of energy for this tissue, we tested
      the hypothesis that physiologic MLT levels, EPA, or CLA injected intravenously,
      inhibit FA uptake in rat skeletal muscle in vivo. We used a surgical technique
      for catheterizing the femoral vein in rats that allows rapid blood collection
      from the entire hind limb, while ensuring continuous blood flow to the tissue.
      Blood acid/gas tensions and hematocrit were monitored and remained constant
      during the course of each experiment. The MLT, EPA, and CLA inhibited FA uptake
      by the tissue and lowered cAMP values. Glucose uptake and glycerol production in
      the hind limb were not affected. These investigations suggest a novel role for
      MLT, omega-3 FAs, and CLA in the regulation of FA transport and fat metabolism in
      skeletal muscle.

PMID- 12784855
TI  - Pathogenesis of mouse hepatitis virus infection in gamma interferon-deficient
      mice is modulated by co-infection with Helicobacter hepaticus.
AB  - Gamma interferon-deficient (IFN-gamma KO) mice developed a wasting syndrome and
      were found to be co-infected with Helicobacter sp., and a new isolate of mouse
      hepatitis virus (MHV) designated MHV-G. The disease was characterized by
      pleuritis, peritonitis, hepatitis, pneumonia, and meningitis. Initial experiments
      used a cecal homogenate inoculum from the clinical cases that contained H.
      hepaticus and MHV-G to reproduce the development of peritonitis and pleuritis in
      IFN-gamma KO mice. In contrast, immunocompetent mice given the same inoculum
      developed an acute, self-limiting infection and remained clinically normal. This
      result confirmed the importance of IFN-gamma in preventing chronic infection and
      limiting viral dissemination. To understand the role of both agents in the
      development of peritonitis and pleuritis, IFN-gamma KO mice were infected with
      either agent or were co-infected with H. hepaticus and MHV-G. Infection with MHV
      G induced a multisystemic infection similar to that described in the original
      cases, with multifocal hepatic necrosis, acute necrotizing and inflammatory
      lesions of the gastrointestinal tract, and acute peritonitis and pleuritis with
      adhesions on the serosal surfaces of the viscera. However, mice given H.
      hepaticus alone had minimal pathologic changes even though the organism was
      consistently detected in the cecum or feces. Although co-infection with H.
      hepaticus and MHV-G induced lesions similar to those associated with MHV-G alone,
      the pathogenesis of the MHV infection was modified. Helicobacter hepaticus
      appeared to reduce the severity of MHV-induced lesions during the acute phase of
      infection, and exacerbated hepatitis and meningitis at the later time point. We
      conclude that infection of IFN-gamma KO mice with MHV-G results in multisystemic
      infection with peritonitis, pleuritis, and adhesions due to the aberrant immune
      response in these mice. In addition, co-infection of these mice with H. hepaticus
      results in alterations in the pathogenesis of MHV-G infection.

PMID- 12784856
TI  - Vascular leak syndrome of Sprague-Dawley rats in a mandibular distraction
      osteogenesis study.
AB  - Vascular leak syndrome (VLS) is a common and often fatal sequela of multiple bone
      traumas, and of infectious, toxic, and allergic insults in human patients.
      Although an animal model for VLS has not been fully established, rats have shown
      sensitivity to the syndrome that approximates that of the human population. We
      describe cases of VLS in three-month-old adult and one-month-old Sprague-Dawley
      rats in an osteogenesis study aimed at optimizing correction of bone hypoplasias
      and other craniofacial deformities in children, using a mandibular distraction
      device. In the study reported here, VLS was diagnosed in 40% of the rats that
      were necropsied after dying or being euthanized early, subsequent to mandibular
      osteotomy, a procedure that involves minimal bone trauma. The gross and
      histologic findings, as well as the clinical course of VLS in the rats of the
      osteogenesis study, were similar to those of documented human cases. Hence, the
      rat may be a useful animal model to h elp characterize the physiologic and
      molecular events that accompany this syndrome.

PMID- 12784857
TI  - Alopecia attributed to neoplastic ovarian tissue in two ferrets.
AB  - Ferrets with adrenal gland dysfunction have alopecia as their most common
      clinical sign of disease. Two cases of alopecia in neutered female ferrets are
      reported that were associated instead with neoplastic tissue found at the site of
      an ovarian pedicle. Androstenedione and 17-hydroxyprogesterone, but not
      estradiol, concentrations were high in both ferrets. Following surgical resection
      of the abnormal tissue in one ferret, the high hormone values decreased quickly
      and hair regrowth ensued. In both cases, histologic examination revealed features
      consistent with classical sex cord-stromal (gonadostromal) tumors: prominent
      spindle cells, along with polyhedral epithelial cells and cells with vacuolated
      cytoplasm. Although similiar cell types have been described in the adrenal glands
      of ferrets with adrenal-associated endocrinopathy, an ovarian origin for the
      current neoplasms is considered likely on the basis of their anatomic location;
      accessory adrenal tissue has only been described close to an adrenal gland or in
      the cranial perirenal fat of ferrets. Immunohistochemical analysis, using an
      antibody against Mullerian-inhibiting substance, failed to prove definitively the
      source of the steroidogenic cells.

PMID- 12784858
TI  - Cloning of an alkaline lipase gene from Penicillium cyclopium and its expression
      in Escherichia coli.
AB  - The gene encoding an alkaline lipase of Penicillium cyclopium PG37 was cloned
      with four steps of PCR amplification based on different principles. The cloned
      gene was 1,480 nucleotides in length, consisted of 94 bp of promoter region, and
      had 6 exons and 5 short introns ranging from 50 to 70 nucleotides. The open
      reading frame encoded a protein of 285 amino acid residues consisting of a 27-AA
      signal peptide and a 258-AA mature peptide, with a conserved motif of Gly-X-Ser-X
      Gly shared by all types of alkaline lipases. However, this protein had a low
      homology with lipases of P. camembertii (22.9%), Humicola lanuginosa (25.6%), and
      Rhizomucor miehei (22.3%) at the amino acid level. The mature peptide-encoding
      cDNA was cloned and expressed in Escherichia coli on pET-30a for confirmation. A
      distinct band with a M.W. of 33 kDa was detected on SDS-PAGE. Results of a
      Western blot analysis and an enzyme activity assay verified the recombinant 33
      kDa protein as an alkaline lipase. Its catalytic properties were not changed when
      compared with its natural counterpart.

PMID- 12784859
TI  - Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as
      inhibitors of oxidosqualene and squalene-hopene cyclases.
AB  - Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene
      (OS) and conjugated and non-conjugated phenylthio derivatives of OS were
      obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces
      cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of
      Alicyclobacillus acidocaldarius squalene-hopene cyclase (SHC) (EC 5.4.99.-),
      contain the reactive function adjacent to carbons involved in the formation of
      the third and the fourth cycle during OS cyclization. All the new compounds are
      inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated
      methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas
      most of the phenylthio derivatives were especially active toward SHC.

PMID- 12784860
TI  - Evaluation of apolipoprotein A-I kinetics in rabbits in vivo using in situ and
      exogenous radioiodination methods.
AB  - The kinetics of in vivo clearance of apolipoprotein (apo) A-I radioiodinated by
      the iodine monochloride (ICI) method of McFarlane [McFarlane, A.S. (1958)
      Efficient Trace-Labelling of Proteins with Iodine, Nature 182, 53] as modified by
      Bilheimer and co-workers [Bilheimer, D.W., Eisenberg, S., and Levy, R.I. (1972)
      The Metabolism of Very Low Density Lipoprotein Proteins. I. Preliminary in vitro
      and in vivo Observations, Biochim. Biophys. Acta 260, 212-221] and by using the
      IODO Beads Iodination Reagent were evaluated in rabbits. Both human apoA-I and
      rabbit HDL radioiodinated by the IODO Beads Iodination Reagent were cleared
      faster from plasma of rabbits than those radiolabeled by the ICI method. However,
      the different radiolabeling procedures in the ICI method, i.e., apoA-I
      radiolabeled either exogenously or in situ as a part of intact HDL, were not
      associated with a significant difference in the in vivo kinetics of apoA-I in
      rabbits if apoA-I was prepared by the guanidine HCI method and used fresh. 125I
      ApoA-I subjected to delipidation and lyophilization was cleared only slightly
      faster from the plasma of rabbits than fresh 125I-apoA-I. We also found that apoA
      I separated by the guanidine HCI method and used fresh was cleared faster from
      the plasma of rabbits when it was injected as free apoA-I without adding serum
      albumin or after in vitro incubation with rabbit HDL than when injected after
      reassociation with rabbit plasma. We conclude that the ICI method is a more
      appropriate radioiodination method for studying the in vivo kinetics of HDL than
      the IODO Beads Iodination Reagent and that the in vitro incubation conditions
      before injection are important factors that affect the in vivo kinetics of apo A
      I.

PMID- 12784863
TI  - Effect of temperature and addition of alpha-tocopherol on the oxidation of
      trilinolein model systems.
AB  - The effects of temperature and addition of alpha-tocopherol were evaluated in
      trilinolein model systems through quantification of oxidized TAG monomers,
      dimers, and polymers following oxidation at different temperatures. Samples of
      trilinolein without and with 250 and 500 mg/kg alpha-tocopherol added were stored
      at 25, 60, and 100 degrees C. Quantification of oxidized monomers, dimers, and
      polymers by a combination of adsorption and exclusion chromatography provided a
      useful measurement for studying the evolution of oxidation. Results showed that
      the amounts of primary oxidation compounds (trilinolein oxidized monomers) that
      accumulated during the induction period decreased as the temperature increased,
      indicating that the slope of the initial linear stage of oxidation depended on
      temperature. The end of the induction period was marked by a sharp increase in
      the levels of total oxidation compounds, the initiation of polymerization, and
      the loss of alpha-tocopherol. Addition of alpha-tocopherol did not prevent, but
      rather delayed, formation of trilinolein oxidized monomers and the initiation of
      polymerization.

PMID- 12784862
TI  - Antioxidant action of a lipophilic nitroxyl radical, cyclohexane-1-spiro-2'-(4'
      oxyimidazolidine-1'-oxyl) -5'-spiro-1"-cyclohexane, against lipid peroxidation
      under hypoxic conditions.
AB  - Nitroxyl radicals are known to act as radical scavenging antioxidants. In the
      present study, a lipophilic nitroxyl radical, cyclohexane-1-spiro-2'-(4'
      oxyimidazolidine-1'-oxyl)-5'-spiro-1"-cyclohexane (nitroxyl radical I) was
      synthesized and its antioxidant capacity was assessed in comparison with a
      hydrophilic nitroxyl radical, 4-hydroxy-2,2,6,6-tetra-methylpiperidine-N-oxyl
      (Tempol). Both nitroxyl radical I and Tempol inhibited methyl linoleate oxidation
      induced by free radicals, and the efficacy increased with decreasing partial
      pressure of oxygen, the effect being more pronounced for nitroxyl radical I than
      Tempol. Their hydroxylamines inhibited lipid peroxidation more effectively than
      their corresponding parent nitroxyl radicals. In liposomal membranes, a
      synergistic effect was observed in the combination of nitroxyl radical I with
      ascorbic acid, whereas only an additive effect was observed between Tempol and
      ascorbic acid. The present study suggests that nitroxyl radical I and its
      hydroxylamine may act as potent antioxidants, especially in combination with
      ascorbic acid under hypoxic conditions.

PMID- 12784861
TI  - Protective action on human LDL against oxidation and glycation by four
      organosulfur compounds derived from garlic.
AB  - Human LDL were used to study the protective action of four organosulfur compounds
      (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N
      acetylcysteine, NAC) derived from garlic against oxidation and glycation. The
      four organosulfur compounds significantly inhibited superoxide production by
      xanthine-xanthine oxidase (P < 0.05) and showed marked copper-chelating
      capability. DAS and DADS exhibited greater antioxidant activities against copper-
      and amphotericin B-induced LDL oxidation (P < 0.05) than SEC and NAC. However,
      SEC and NAC were more effective in sparing LDL alpha-tocopherol (P < 0.05). When
      oxidation was minimized, SEC was the most powerful agent against LDL glycation (P
      < 0.05); however, DADS was superior to other agents in suppressing both oxidation
      and glycation when LDL oxidation occurred simultaneously with glycation. These
      results suggest that the four organosulfur compounds derived from garlic are
      potent agents for protecting LDL against oxidation and glycation, and that they
      may benefit patients with diabetes mellitus or cardiovascular diseases by
      preventing complications.

PMID- 12784864
TI  - Photochemical oxidation and autoxidation of chlorophyll phytyl side chain in
      senescent phytoplanktonic cells: potential sources of several acyclic isoprenoid
      compounds in the marine environment.
AB  - Visible light-induced degradation of the chlorophyll phytyl side chain was
      studied in senescent cells of two phytoplanktonic strains (Skeletonema costatum
      and Thalassiosira weissflogii). Particular attention was paid to the induction of
      autoxidation processes on the phytyl chain and its photoproducts by
      photochemically produced hydroperoxides. The combination of photochemical
      oxidation and autoxidation reactions resulted in the production of several
      acyclic isoprenoid compounds that have been unambiguously identified by
      comparison of their retention times and mass spectra with those of appropriate
      standards. Various mechanisms are proposed to explain the formation of these
      oxidation products. These processes appear to be potential sources of numerous
      oxidized acyclic isoprenoids that previously have been detected in lacustrine and
      marine environments. Some oxidation products newly described or whose presence in
      natural samples was never reported in the literature were then sought in
      particulate matter, sediment, and microbial mat samples. The results obtained
      supported the significance of photochemical oxidation and autoxidation of
      phytoplanktonic chlorophyll phytyl side chain in the marine environment.

PMID- 12784865
TI  - Isolation of unsaturated diols after oxidation of conjugated linoleic acid with
      peroxygenase.
AB  - Oat seeds are a rich source of peroxygenase, an iron heme enzyme that
      participates in oxylipin metabolism in plants. An isomer of CLA, 9(Z),11 (E)
      octadecadienoic acid (1), believed to have anticarcinogenic activity, was used as
      a substrate for peroxygenase in an aqueous medium using t-butyl hydroperoxide as
      the oxidant. After acidification of the reaction medium, the products were
      extracted with ethyl ether, converted to their methyl esters, and characterized
      using HPLC. Major products after reaction for 24 h showed resonances from 1H NMR
      spectroscopy that were further downfield than the expected epoxides and were
      thought to be diol hydrolysis products. However, analyses by HPLC with
      atmospheric pressure chemical ionization MS (APCI-MS) of the putative allylic
      diols or their bis-trimethylsilyl ether derivatives gave incorrect M.W. The M.W.
      of the diols could be obtained by APCI-MS after removal of unsaturation by
      hydrogenation or by EI-MS after conversion of the allylic 1,2-diols to cyclic
      methyl boronic esters. Data from MS in conjunction with analyses using 1H and 13C
      NMR showed that the methylated products from 1 were methyl 9,10(threo)-dihydroxy
      11 (E)-octadecenoate, methyl 9,10(erythro)-dihydroxy-11(E)-octadecenoate, methyl
      9,12(erythro)-dihydroxy-10(E)-octadecenoate, and methyl 9,12(threo)-dihydroxy
      10(E)-octadecenoate. Solid-phase extraction without prior acidification and
      conversion of the products to methyl esters allowed identification of the
      following epoxides: methyl 9,10(Z)-epoxy-11 (E)-octadecenoate (6M), methyl
      9,10(E)-epoxy-11 (E)-octadecenoate, and methyl 11,12(E)-epoxy-9(Z)-octadecenoate.
      At times of up to at least 6 h, 6M accounted for approximately 90% of the epoxide
      product. Product analysis after the hydrolysis of isolated epoxide 6M showed that
      hydrolysis of epoxide 6 could largely account for the diol products obtained from
      the acidified reaction mixtures.

PMID- 12784866
TI  - Eicosapentaenoic acid-induced apoptosis depends on acyl CoA-synthetase.
AB  - Marine n-3 FA are known to inhibit proliferation or induce cell death in several
      cancer cell lines. We have previously reported that EPA promotes apoptosis in the
      lymphoma cell line Ramos, whereas the U-698 cell line is insensitive to EPA.
      Furthermore, acyl-CoA synthetase (ACS) is expressed to a higher extent in Ramos
      cells compared to U-698 cells. To investigate the importance of ACS in EPA
      induced apoptosis, we incubated Ramos cells with triacsin C, an inhibitor of ACS.
      This caused a 70% reduction in the amount of cell-associated EPA and diminished
      activation of EPA. In addition, triacsin C caused a 90% reduction in EPA-induced
      apoptosis. Several different approaches were tried to overexpress ACS4 in EPA
      insensitive lymphoma cell lines, but we did not obtain viable cells with high
      expression of acyl-CoA activation. However, we show that overexpression of ACS4
      in the more robust COS-1 cells caused up to a fivefold increase in activation of
      EPA and a 67% increase in the amount of cell-associated radiolabeled EPA.
      Furthermore, we observed 28% elevated cellular level of TAG in EPA-incubated COS
      1 cells overexpressing ACS4. The present study provides new information about ACS
      as an important enzyme for EPA-induced apoptosis in Ramos cells. Our data offer a
      potential mechanism that may explain the effect of dietary marine n-3 PUFA on
      growth of certain malignant cells.

PMID- 12784867
TI  - Ethyl arachidonate is the predominant fatty acid ethyl ester in the brains of
      alcohol-intoxicated subjects at autopsy.
AB  - The role of fatty acid ethyl esters (FAEE), the nonoxidative ethanol metabolites,
      as mediators of alcohol-induced organ damage is increasingly being recognized.
      FAEE are detectable in the blood and in liver and adipose tissue after ethanol
      ingestion, and on that basis, FAEE can be used as markers of ethanol intake. In
      this study, 10 samples of human brain were collected at autopsy at the
      Massachusetts Medical Examiner's Office and analyzed for FAEE. FAEE were isolated
      and quantified as mass per gram of wet weight. The blood ethanol level was also
      obtained in each case along with the other drugs detected in routine postmortem
      toxicology screening tests. Ethyl arachidonate was the predominant FAEE species
      in the brain, representing up to 77.4% of total FAEE in the brain. The percent
      age of ethyl arachidonate of the total FAEE in the brain was significantly higher
      than what has been found in all other organs and tissues previously analyzed.
      Linoleate, the precursor of arachidonate, was a poor substrate for FAEE
      synthesis, as the percentage of ethyl linoleate of the total FAEE content was
      extremely low. Thus, this reflects preferred incorporation of arachidonate into
      newly synthesized FAEE in the brain. Since arachidonate is derived from
      linoleate, which is depleted in FAEE while arachidonate is enriched, the
      synthesis of FAEE may be linked to the desaturation and elongation of linoleate
      to arachidonate.

PMID- 12784868
TI  - Effects of red wine consumption on kidney FA composition.
AB  - We studied the effects of red wine consumption on the FA composition of rat
      kidney. Four groups of adult male rats were fed a balanced diet for 10 wk. The
      drinking fluid was water (control), red wine, alcohol-free red wine, or ethanol
      (12.5%, vol/vol). FA composition, lipid peroxidation, and cytochrome P450 content
      were determined in the kidney. The antioxidant capacity of plasma was also
      measured. Ethanol decreased the content of long-chain PUFA, whereas red wine
      maintained the levels of arachidonic (20:4n-6) and eicosapentaenoic (20:5n-3)
      acids and alcohol-free red wine significantly increased the levels of 20:4n-6.
      Lipid peroxidation in the red wine and alcohol-free red wine groups was
      significantly lower than that of both the control and ethanol groups. The
      diminished renal lipid peroxidation was associated with an increased antioxidant
      capacity of plasma. Renal cytochrome P450 was elevated by 50% in the ethanol
      group and diminished by 20% in the alcohol-free red wine group. These data
      suggest that moderate red wine consumption could contribute to the preservation
      of the contents of n-3 and n-6 PUFA, particularly 20:4n-6, in rat kidney.
      Although ethanol increased the content of cytochrome P450 in the kidney, this
      effect was eliminated by the nonalcoholic components of red wine.

PMID- 12784869
TI  - Functionalization of unactivated carbons in 3alpha,6- and 3alpha,24-dihydroxy
      5beta-cholane derivatives by dimethyldioxirane.
AB  - Direct remote functionalization of unactivated carbons by dimethyldioxirane
      (DMDO) was examined for 3alpha,6- and 3alpha,24-dihydroxy-5beta-cholane
      derivatives. DMDO oxidation of stereoisomeric methyl 3alpha,6-diacetoxy-5beta
      cholanoates caused the direct, unexpected 14alpha- and 17alpha-hydroxylations, in
      analogy with that of the 5alpha-H analogs, regardless of the differences in
      stereochemical configuration of the A/B-ring junction and of the acetoxyl groups
      at C-3 and C-6. On the other hand, the ester derivatives of 3alpha,24-dihydroxy
      5beta-cholane with DMDO were transformed into the corresponding 5beta-, 14alpha-,
      and 17alpha-hydroxy compounds, whereas the ether derivatives yielded the 5beta
      hydroxy, 3-oxo, and C-24 oxidized products, accompanied by their dehydrated ones.

PMID- 12784870
TI  - An in vitro method for studying the proliferation and differentiation of Atlantic
      salmon preadipocytes.
AB  - The aim of the present study was to develop a cell culture system for studying
      the proliferation and differentiation of preadipocytes isolated from Atlantic
      salmon adipose tissue. The expression of proliferating cell nuclear antigen
      (PCNA) was used as a marker for cell proliferation. The cells started to
      proliferate within 48 h after seeding and continued to proliferate throughout the
      culture period of 2 wk. Undifferentiated preadipocytes showed a fibroblast-like
      morphology with a homogeneous cytoplasm devoid of lipid droplets. At confluence,
      an exogenous lipid mixture was added to the cell cultures. The preadipocytes
      became larger and rounder during the subsequent days, and the cytoplasm gradually
      filled with lipid-rich droplets. These droplets were revealed by oil red O
      staining. Immunocytochemical staining showed that differentiated adipocytes
      expressed detectable levels of the three regulatory proteins associated with
      adipocyte differentiation: peroxisome proliferator-activated receptor gamma
      (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and leptin. The
      cells also showed activity of glycerol-3-phosphate dehydrogenase (GPDH) (EC
      1.1.1.8), a biochemical marker of adipocyte differentiation. The morphological
      and biochemical data presented here show that fish preadipocytes have properties
      that are similar to those of preadipocytes in mammals. We conclude therefore that
      salmon adipose tissue contains a sizable population of preadipocytes. Exogenous
      lipids promote the activation of adipose-related genes and induce the
      differentiation of fish preadipocytes in vitro.

PMID- 12784871
TI  - Glioblastoma multiforme: introduction.

PMID- 12784872
TI  - Astrocyte differentiation states and glioma formation.
AB  - Gliomas are the most common primary malignancy in human central nervous system.
      Many similarities in cell morphology and expression of markers exist between
      cancerous cells and normal undifferentiated progenitor cells. At the molecular
      level, many important gene products are causally implicated in both the glial
      differentiation process and glial neoplasm formation. These observations raise
      the question of to what degree cell differentiation state influences glioma
      formation. In this review, we discuss new insights into the parallels between
      glial differentiation and glioma formation as well as the potential application
      of differentiation-inducing therapy.

PMID- 12784873
TI  - Classification of glioblastoma multiforme in adults by molecular genetics.
AB  - Recent advances in cytogenetic and molecular methodologies have elucidated
      certain principal characteristics of oncogenesis in glioblastoma multiforme. The
      earliest clues implicate gene sequence alterations, such as gene amplification
      and numerical gain or loss of function in specific chromosomes. Genetic
      classification and expression patterns have thus been constructed, conferring the
      likelihood of two types of glioblastoma, primary (de novo) as opposed to
      secondary (evolving from a pre-existing low-grade glioma). The former group of
      tumors exhibits more frequent occurrences of EGFR gene amplification, whereas the
      latter group relies strongly on TP53 gene inactivation. Many other tumor
      suppressor genes and oncogenes have been discovered. Most gene alterations induce
      cell cycle dysfunction on a complex molecular level. Further insight into tumor
      genesis by means of genomic assays may aid in predicting the clinical behavior of
      glioblastoma and in providing individualized potential targets for therapeutic
      agents.

PMID- 12784874
TI  - Intraoperative imaging in glioblastoma resection.
AB  - The use of intraoperative imaging (IOI) in neurosurgical practice is proving to
      be yet another important advance in the evolution of brain tumor resection,
      particularly for the most common adult primary brain tumor--glioblastoma (GBM).
      The number of surgeons using IOI continues to increase, and the experience to
      date affords an opportunity to assess the value of the various techniques used
      for IOI.

PMID- 12784875
TI  - Molecular epidemiology of glioblastoma.
AB  - Glioblastoma (GBM) is the most important primary brain tumor, both in terms of
      its incidence and its devastating impact on the unfortunate patients who have it.
      Although several well-defined hereditary syndromes predispose to malignant
      gliomas, most cases occur in the absence of a such a syndrome. The role of
      environmental factors, based on the known associations to date, also appears
      limited when compared with the total number of patients affected. It is clear
      that much remains to be discovered to better elucidate the causes of GBM, but the
      increasing recognition of molecular subtypes may help advance this field. This
      review highlights current insights into the molecular epidemiology of GBM.

PMID- 12784876
TI  - Pediatric high-grade gliomas.
AB  - High-grade gliomas, including glioblastoma multiforme, anaplastic astrocytoma,
      and intrinsic pontine, are very difficult to treat in children. Despite
      aggressive treatment with multimodal therapy, most children with these diseases
      do not survive. Data from published series support aggressive surgical resection
      when clinically feasible. Patients who have had aggressive resections tend to
      have a longer survival than those who have undergone only biopsies or partial
      resections. Almost all patients with high-grade gliomas respond to radiation
      therapy, and it is the current mainstay of adjuvant therapy. Radiation therapy
      also tends to prolong survival, but it is rarely curative. Although responses to
      chemotherapy have been demonstrated, there are no compelling data indicating that
      it prolongs survival for this group of patients. Current and proposed studies are
      combining radiation therapy and/or chemotherapy with agents that have shown
      preclinical promise as radiosensitizers, anti-angiogenesis factors, growth factor
      receptor inhibitors, and free radical inducers. Other biologic therapies,
      including gene therapy, are also being investigated. Improved survival for these
      patients will likely require combined therapy that includes novel treatment.

PMID- 12784877
TI  - Current surgical management of glioblastoma.
AB  - Surgical resection is a critical aspect of the management of a patient with a
      glioblastoma (GBM). An intimate knowledge of the anatomy of a GBM, as well as
      familiarity with particular surgical techniques and adjunctive technologies is
      required for safe surgical resection. The goals of resection include diagnosis,
      relief of mass effect, and cytoreduction. A recent study showed that resection of
      98% or more of the tumor mass can result in a statistically significant survival
      advantage. Even in functionally critical areas, "gross total" resections are
      possible if proper techniques are employed. It is recommended that a "gross
      total" resection of the enhancing portion of a GBM be performed whenever
      possible. With this philosophy, the mortality rate is 3% and the rate of major
      neurologic morbidity is less than 10%.

PMID- 12784878
TI  - FAK signaling in anaplastic astrocytoma and glioblastoma tumors.
AB  - Focal adhesion kinase (FAK) is a non-receptor cytoplasmic-tyrosine kinase that is
      activated by several different cell surface receptors shown to be upregulated on
      glioblastoma cells (integrins alpha(v)beta3 and alpha(v)beta5, and the epidermal
      growth factor receptor). Activated FAK can signal through several different
      signaling pathways, which are reviewed here. Published data are summarized that
      have demonstrated 1) elevated FAK expression in anaplastic astrocytoma and
      glioblastoma tumor biopsy samples, 2) a role for FAK in the promotion of
      glioblastoma cell proliferation, survival and migration in vitro, and 3) a role
      for FAK in the promotion of glioblastoma cell proliferation in vivo in an animal
      model. The available data suggests that increased levels of FAK protein and
      activity may contribute to an increased ERK activity and cell proliferation in
      vivo in these tumors.

PMID- 12784879
TI  - Imaging glioblastoma multiforme.
AB  - Glioblastoma multiforme are infiltrative lesions that have a high degree of
      heterogeneity, both within and between different patients. Imaging is critical
      for all phases in the evaluation and treatment of these lesions, but has been
      limited in providing information that is reliable enough to stratify patients
      into groups with uniform behavior and to predict outcome. Although magnetic
      resonance imaging is the method of choice for visualizing anatomic features of
      the lesion, its results are ambiguous in terms of defining the functional
      characteristics of the lesion and distinguishing tumor from treatment induced
      necrosis. Recent advances in magnetic resonance have made possible the routine
      acquisition of physiological data such as perfusion- and diffusion-weighted
      images and of metabolic data such as water suppressed proton spectroscopic
      images. These provide quantitative measurements that are more closely related to
      the biological properties of the tumor and reflect changes in tumor vascularity,
      cellularity and proliferation that are associated with tumor progression. As the
      molecular properties that influence invasion and neoplastic transformation are
      elucidated, it is critical that noninvasive imaging techniques are available for
      investigating new therapies and tailoring treatment to individual patient
      characteristics. The data obtained from patients with glioblastoma multiforme
      have already demonstrated that these new magnetic resonance techniques are able
      to contribute to diagnosis, characterization of malignant potential, treatment
      planning and assessment of response to therapy.

PMID- 12784880
TI  - Novel method for continuous cell separation by density gradient centrifugation:
      evaluation of a miniature separation column.
AB  - A compact bench-top model of the centrifuge enables continuous cell separation
      based on density differences. The apparatus holds a small separation disk
      equipped with a circular channel (8 mL capacity) separated by a septum. A set of
      isotonic Percoll media with different densities is continuously introduced at one
      terminal and collected from the other. Under a centrifugal force field, cell
      suspension introduced into the proximal portion of the channel results in
      continuous separation of cells according to their densities. The performance of
      the apparatus was demonstrated with the separation of human buffy coat containing
      nucleated cells (>10(8)) among a large population (10(10)) of RBC. The results
      indicated that the method is capable of separating a large number of nucleated
      cells, with minimum damage, for a few hours of operation wherein neutrophils are
      well resolved from lymphocytes. The method may be applied to other types of
      samples including cord blood, blood from small animals, cultured cells,
      pancreatic beta cell islets, malaria parasites, sperm cells, etc.

PMID- 12784881
TI  - Contamination of ribosome inactivating proteins with ribonucleases, separated by
      affinity chromatography on red sepharose.
AB  - Three preparations of type 1 ribosome inactivating proteins (RIPs), namely,
      agrostin, saporin, and luffin, were subjected to affinity chromatography on Red
      Sepharose and eluted with a linear concentration gradient of NaCl in 10 mM Tris
      HCl buffer (pH 7.4). The eluate was assayed for ability to inhibit translation in
      a cell-free rabbit reticulocyte lysate system which measures RIP activity, and
      for ability to hydrolyze yeast transfer RNA which measures RNase activity. It was
      found that, in all three RIP preparations, the peak of RIP activity, which
      coincided with the peak of absorbance at 280 nm, was eluted earlier than the peak
      of RNase activity. It appears that RNase is a possible contaminant of ribosome
      inactivating protein preparations and that this contamination can be minimized by
      using Red Sepharose.

PMID- 12784882
TI  - Purification and characterization of Ulva pertusa Kjellm alkaline phosphatase.
AB  - The activity of alkaline phosphatase (ALP, EC 3.1.3.1.) was found in seaweeds,
      including five kinds of green alga, eighteen kinds of red alga, and six kinds of
      brown alga, collected from the seaside of Dalian in China. The enzyme was
      purified 1230-fold from Ulva pertusa Kjellm. It had a specific activity of 48.6
      U/mg protein and was proven to be homogeneous by SDS-PAGE with a subunit
      molecular mass of 19.5 kDa. The activity of ALP peaked at pH9.8, and was
      completely inhibited by DTT and partly by NBS. The Michaelis-Menten constant Km
      and the maximum reaction velocity Vmax, at pH 9.8 and 37 degrees C were 0.950 mM
      and 5.00 microM/min, respectively.

PMID- 12784883
TI  - A method for large scale purification of turnip peroxidase and its
      characterization.
AB  - Purification of peroxidase has been carried out since 1960 from different sources
      and with different methods. Ion exchange, affinity, hydrophobic, and metal
      affinity chromatography are known, to our knowledge. The present method,
      developed in this study, is three-phase partitioning, a novel technique to
      separate protein directly from a large volume of crude suspension. It has been
      observed that interfacing phase with a metal makes this technique highly
      selective. Turnip peroxidase purified with this method has 512 units/mg with
      20.3% recovery. The natural proteins containing histidine or cystine are often
      purified by immobilized metal affinity chromatography. The purification of turnip
      peroxidase with the three-phase partitioning technique is based on immobilized
      metal affinity chromatography and is used for large-scale purification. The
      present method, described here, would prove its value in purifying an
      industrially important enzyme on a large scale from a crude suspension. The
      enzyme purified with this technique showed two bands on SDS- PAGE, which showed a
      molecular weight of approx. 39KD. Enzyme showed maximum purification with Cu++
      metal and had a maximum activity at pH 6.0. The enzyme has an affinity towards
      hydrogen peroxide as its substrate in the presence of orthodianisidine as a
      chromogenic substrate. Enzyme activity was enhanced with calcium and magnesium,
      whereas sodium, potassium, and manganese inhibit the enzyme activity.

PMID- 12784884
TI  - Purification and characterization of acetylcholinesterase from the Lake Van fish
      (Chalcalburnus tarichii Pallas, 1811).
AB  - In this study, acetylcholinesterase (AChE; EC 3.1.1.7) was purified from plasma
      and erythrocytes in the Lake Van fish (Chalcalburnus tarichii P.1811) by affinity
      chromatography. Enzymatic activity was spectrophotometrically measured according
      to Ellman's method, at 412 nm. Then, the optimal pH and temperature of the enzyme
      was determined. According to the results, the optimal pH and the optimum
      temperature were 8.0 and 25 degrees C, respectively. In order to control the
      purification of the enzyme, sodium dodecyl-sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was done. SDS-PAGE showed a single band for enzyme.
      The purification rates for plasma AChE and erythrocyte AChE are 3251.6 and 8500,
      respectively.

PMID- 12784885
TI  - Defining dissociations.

PMID- 12784886
TI  - Written language as a window into residual language deficits: a study of children
      with persistent and residual speech and language impairments.
AB  - Previous work has suggested that, because writing is a late-acquired and complex
      skill, it may be a particularly sensitive index of language difficulties in
      children. Evidence in support of this view was obtained in a study contrasting
      161 normally-developing control children aged from 7.5 to 13 years with 75 twin
      children of the same age who either had specific speech-language impairments, or
      were co-twins of affected children. Written narratives were elicited from
      children using a sequence of five photographs depicting a simple story, and were
      analysed for grammatical complexity and accuracy, intelligibility, and semantic
      content. Only 42 of the twins could spell well enough to attempt the narrative
      task. Some co-twins of affected children had deficits in written language,
      despite normal performance on oral language tests. Most children with language
      impairments were poor at writing, with particularly marked deficits on a measure
      of spelling and punctuation. Children with language impairments made a relatively
      high proportion of phonologically inaccurate spelling errors when compared with
      younger children at a similar vocabulary level. Those who did poorly on a nonword
      repetition test were especially likely to have poor written language. However,
      four children with pure speech difficulties produced age-appropriate written
      narratives.

PMID- 12784887
TI  - Recognition memory for hand positions and spatial locations in patients with
      Huntington's disease: differential visuospatial memory impairment?
AB  - Allocentric and egocentric memory was investigated in patients with Huntington's
      disease (HD) and matched controls. Patients with HD and age- and education
      matched healthy normal controls (NC) were administered two visuospatial
      recognition memory tasks, one assessing memory for hand positions (egocentric)
      and the other assessing memory for spatial locations (allocentric). HD patients
      showed normal primacy and recency effects, but their overall performance was
      impaired relative to controls on both tasks. Correlation analyses indicated that
      HD patients' performance on the Hand Position Memory task, but not the Spatial
      Location Memory task, was associated with global cognitive status (Mattis
      Dementia Rating Scale) and disease severity (Shoulson and Fahn Rating Scale), and
      HD patients' performances on the two tasks were not associated. Results provide
      preliminary support for the role of the caudate nucleus in both allocentric and
      egocentric spatial memory.

PMID- 12784888
TI  - Cognitive, lexical and morpho-syntactic profiles of Israeli children with
      Williams syndrome.
AB  - This paper investigated the cognitive, lexical and morpho-syntactic profiles of
      school-age Israeli children with confirmed diagnosis of Williams syndrome (WS).
      Children with retardation of unknown etiologies were individually matched to the
      children with WS. The findings suggest a cognitive profile that was similar to
      the profile reported for English-speaking children with WS, whose unique features
      were seen mainly in the discrepancy between verbal IQ and performance IQ and in
      relatively preserved face recognition abilities (Frangiskakis et al., 1996;
      Mervis et al., 1999). Contrary to previous findings, cognitive, lexical and
      morpho-syntactic profiles of individual children were rather similar, confirming
      the findings that were based on matched-pairs comparisons.

PMID- 12784889
TI  - Cognitive structure of executive deficits in frontally lesioned head trauma
      patients performing activities of daily living.
AB  - OBJECTIVE: Executive functions in activities of daily living (ADL) were
      investigated in 10 patients with frontal lobe lesions after a mild to severe
      closed head injury (CHI). METHOD: The CHI patients were compared to 12 normal
      controls with a neuropsychological test battery, a script recitation task and a
      realistic simulation of complex multitask ADL (planning and preparing a meal).
      RESULTS: Though the CHI patients were significantly slow on one test and subject
      to interference on an attention test with parametric testing, the groups did not
      differ on any neuropsychological test with non parametric testing. However, the
      CHI patients manifested marked anomalies in the meal preparation task. While
      small sequences of actions were easily produced, large action sets could not be
      correctly executed. CONCLUSION: An outstanding deficit in strategic planning and
      prospective memory appears to be an important underpinning of the impairment of
      ADL observed in CHI patients with frontal lobe lesions.

PMID- 12784890
TI  - Hemispherical asymmetry in human SMA during voluntary simple unilateral
      movements. An fMRI study.
AB  - Functional magnetic resonance imaging (fMRI) was used to test the hypothesis of a
      prevailing role of left supplementary motor area (SMA) during voluntary right and
      left finger movements, in line with subjects' right hand preference. fMRI
      responses were quantified using task-related percent increase of the signal from
      statistically activated voxels in primary somatosensory (S1), primary motor (M1),
      and SMA cortical regions. Regional analysis comprised both extension and
      intensity of statistically activated groups of voxels. Results replicated
      previous fMRI evidence. Right M1 and S1 were much more activated during left
      rather than right movements, whereas such a difference was less evident in left
      M1 and S1. A novel finding consisted in an analogous functional hemispherical
      asymmetry in left and right SMA. Strikingly, left SMA activation did not differ
      statistically during right (contralateral) vs. left (ipsilateral) movements. It
      was concluded that, in right-handed subjects, left SMA plays a prevailing role in
      the control of voluntary movements.

PMID- 12784891
TI  - The control of sequential aiming movements: the influence of practice and manual
      asymmetries on the one-target advantage.
AB  - The present experiment was conducted to explore the effect of practice on the one
      target advantage in manual aiming, as well as asymmetries in intermanual transfer
      of training. Reaction and movement times for the first movement were longer in
      the 2-target than in the 1-target task, regardless of the amount of practice,
      hand preference and practice hand. When two movements were required, peak
      velocity was lower and, proportionally, more time was spent after peak velocity.
      Our kinematic results suggest that the one-target advantage is related to both
      predefined strategies as well as movement implementation processes during
      execution. Therefore, an integration of advance planning and on-line explanations
      for the one-target advantage is suggested. Regarding manual asymmetries, right
      handers showed more transfer of training from the left to the right hand than
      vice versa. Left-handers exhibited a reversed pattern of asymmetric transfer of
      training to right-handers, but they were more disadvantaged using their non
      dominant hand. These latter two findings have implications for models of manual
      asymmetry and upper limb control.

PMID- 12784892
TI  - Visuospatial deficits due to impaired visual attention: investigation of two
      cases of slowly progressive visuospatial impairment.
AB  - Two patients with slowly progressive visuospatial impairment demonstrated a
      peculiar type of visuoconstructive deficit. The most prominent manifestation
      appeared when handling kanji (logogram) characters and other figurative patterns.
      The patients showed pure agraphia for complex kanji but not for kana
      (syllabogram) or Arabic numerals. Their abilities to read and understand kanji
      characters and to orally describe the structure of a kanji character were
      preserved. They could not draw or copy figures or symbols except for single lines
      or simple symbols, although they could identify and name the targets easily. They
      also performed poorly in such visuoconstructive tasks as the block design subtest
      and matching to sample tests that require the ability to simultaneously attend to
      multiple saliencies. When asked to copy multiple kana characters scattered on a
      sheet of paper, they could correctly describe the location of a particular
      character in relation to the others, but actually wrote each character in grossly
      mislocated positions. These findings suggest that when the patients start
      particular tasks, which require detailed visual analysis, their range of visual
      attention becomes extremely narrow. This task-dependent narrowing and fixation of
      visual attention might explain some of the visuoconstructive symptoms described
      in patients with slowly progressive visuospatial impairment.

PMID- 12784893
TI  - Wanted: fully operational definitions of dissociations in single-case studies.
AB  - In contrast to the careful consideration given to the issue of what we can infer
      from dissociations in single-case studies, the more basic question of how we
      decide whether a dissociation is present has been relatively neglected. Proposals
      are made for fully operational definitions of a deficit, classical and strong
      dissociations, and double dissociations. In developing these definitions it was
      assumed that they should be based on the use of inferential rather than
      descriptive statistical methods. The scope of these definitions is limited to
      typical single-case studies in which patients are compared to control samples of
      a modest size. The operational definition of a classical dissociation
      incorporates a requirement that a patient's performance on Task X is
      significantly different from Task Y, in addition to the "standard" requirement
      that the patient has a deficit on Task X and is within normal limits on Task Y.
      We ran a simulation to estimate the Type I error rates when the criteria for
      dissociations are applied and found these to be low (Type I errors were defined
      as identifying an individual from the control population as having a
      dissociation). The inferential methods for testing whether the various criteria
      are met make use of t-distributions. These methods are contrasted with the
      widespread use of z to test for a deficit or a difference between tasks. In the
      latter approach the statistics of the control sample are treated as parameters;
      this is not appropriate when, as is normally the case, the control sample size is
      modest in size.

PMID- 12784894
TI  - The White House embraces holism.

PMID- 12784895
TI  - Sleep disturbances linked to fibromyalgia.
AB  - Fibromyalgia (FM) is a chronic muscle disorder characterized by muscle aches and
      pain of varying intensities. Sleep disturbances have been recognized as one of
      the probable causes of this disorder. Pharmacological and nonpharmacological
      approaches are often used to manage the symptoms of sleep disturbances. This
      article provides a brief background on FM, discusses the physiology of sleep,
      reviews the current literature on sleep disturbances associated with FM, provides
      insight to interventions that might be beneficial given the data available, and
      recommends ongoing research.

PMID- 12784896
TI  - Improved sleep may reduce arthritis pain.
AB  - Studies indicate that pain interferes with sleep and, in turn, sleep disturbances
      increase pain. Statistics show that up to 60% of those with arthritis experience
      pain during the night. But despite these findings, sleep is not generally
      addressed as a major treatment concern among this population. This article
      reviews the relationship between pain and sleep; sleep issues as they relate to 3
      common types of arthritis--osteoarthritis, rheumatoid arthritis, and
      fibromyalgia; and holistic approaches that may be used by the patient in the self
      management of pain and sleep.

PMID- 12784897
TI  - Family caregivers need support with heart failure patients.
AB  - Millions of family members are serving as caregivers for patients with heart
      failure and the numbers will continue to rise. It appears that caregivers desire
      to be involved in the patient's care even when the caregiving tasks average 8
      hours per day. Burden, stress, and depression have been found to be significantly
      associated with the caregiving role in this population. Decreasing any negative
      aspects of caregiving should be a priority. Alarmingly, caregivers have reported
      being ignored or made to feel like an outsider by health care providers. Nurses
      are in a pivotal position to improve patient and caregiver outcomes by including
      the family caregivers of heart failure patients in all aspects of care and in
      promoting the well being of the caregiver. This article will highlight the
      importance of social support on patient and caregiver outcomes, and second,
      review studies on family caregiving among heart failure patients. Recommendations
      for nursing practice and further research will be discussed.

PMID- 12784898
TI  - Familial research reveals new practice model.
AB  - Three ethnographic studies investigated how families define and practice family
      health within their household and community settings. Synthesis of these findings
      prompted the Family Health Model. It suggests ways to dialogue about the complex
      variables associated with family health and approaches to family-focused
      practice.

PMID- 12784899
TI  - Complementary therapy in chronic wound management: a holistic caring case study
      and praxis model.
AB  - Holistic caring consists of providing care to each aspect of a patient's life
      through the use of therapeutic caring and complementary or alternative healing
      modalities. Since nursing consists of caring for the whole person and not just
      the disease process, consideration of a patient's physical, emotional, social,
      economic, spiritual, and cultural needs is necessary in dealing with any chronic
      health problem such as chronic wounds. In this model case studies presentation,
      the purpose of this article is to discuss the importance of the holistic caring
      approach and the use of complementary and alternative medicine or therapeutic
      modalities in chronic wound management. The use or role of theory in practice
      will also be discussed to emphasize the holistic caring praxis model used in the
      holistic assessment and holistic plan of care for the cases presented. This
      article also presents a framework that will help wound care and holistic nurses
      move from simply the positivist-modernist philosophy to begin to embrace the
      postmodernist philosophy.

PMID- 12784900
TI  - How elderly nursing home residents transcend losses of later life.
AB  - Losses of later life can prove overwhelming to older adults. Some elderly persons
      seem to cope with these losses with a spirit of acceptance and serenity. The
      purpose of this study was to identify qualities in selected nursing home
      residents that allow them to transcend difficulties and continue living with some
      degree of contentment and satisfaction. Qualitative data were obtained in taped
      interviews from 95 functionally impaired residents (mean age 82.16 years).
      Content analysis resulted in several themes supporting the spiritual perspective
      of Reed's theory of self-transcendence: generativity, introjectivity, temporal
      integration, body-transcendence, and relationship with self, others, and a higher
      being.

PMID- 12784901
TI  - Exploring yoga to relieve menopausal symptoms.

PMID- 12784902
TI  - Quantitative EEG and the Frye and Daubert standards of admissibility.
AB  - The 70-year-old Frye standards of "general acceptance" were replaced by the
      Supreme Court's 1993 Daubert criteria of the scientific method, which established
      the standards for admissibility of evidence in Federal Court. The four Daubert
      criteria were: 1- Hypothesis testing, 2- Estimates of error rates, 3- Peer
      reviewed publication and 4- General acceptance (Daubert v. Merrell Dow
      Pharmaceuticals, 61 U.S.LW 4805 (U.S. June 29, 1993)). The present paper starts
      with the Daubert four factors and then matches them, step by step, to the
      scientific peer reviewed literature of quantitative EEG (QEEG) in relation to
      different clinical evaluations. This process shows how the peer reviewed science
      of the Digital EEG and the Quantitative EEG (QEEG) meet all of the Daubert
      standards of scientific knowledge. Furthermore, the science and technical aspects
      of QEEG in measuring the effects of neurological and psychiatric dysfunction also
      match the recent Supreme Court standards of "technical" and "other specialized"
      knowledge (General Electric Co v. Joiner, 1997, Kumho Tire Company, Ltd. v.
      Carmichael, 1999). Finally, it is shown that QEEG scientific knowledge and QEEG
      "technical" and "other specialized" knowledge meet the trilogy standards of the
      Supreme Court rulings in support of QEEG's admissibility as a clinically valid
      method in the evaluation of the nature and extent of neurological and psychiatric
      disorders.

PMID- 12784903
TI  - Infant EEG spectral coherence data during quiet sleep: unrestricted principal
      components analysis--relation of factors to gestational age, medical risk, and
      neurobehavioral status.
AB  - EEG spectral coherence data in quiet sleep of 312 infants were evaluated, at 42
      weeks post-menstrual age. All were medically healthy and living at home by time
      of evaluation. The sample consisted of prematurely bom infants with a wide
      spectrum of underlying risk factors, as well as healthy full-term infants.
      Initial 3040 coherence variables were reduced by principal components analysis in
      an unrestricted manner, which avoided the folding of spectral and spatial
      information into among-subject variance. One hundred fifty factors explained 90%
      of the total variance; 40 Varimax rotated factors explained 65% of the variance
      yielding a 50:1 data reduction. Factor loading patterns ranged from multiple
      spectral bands for a single electrode pair to multiple electrode pairs for a
      single spectral band and all intermediate possibilities. Simple left-right and
      anterior-posterior pairings were not observed within the factor loadings. By
      multiple regression analysis, the 40 factors significantly predicted gestational
      age at birth. By canonical correlation, significant relationships were
      demonstrated between the coherence factors and medical risk factors as well as
      neurobehavioral factors. Using discriminant analysis, the coherence factors
      successfully discriminated between infants with high and low medical risk status
      and between those with the best and worst neurobehavioral status. The two factors
      accounting for the most variance, and chosen across several analyses, indicated
      increased left central-temporal coherence from 6-24 Hz, and increased frontal
      occipital coherence at 10 Hz, for the infants born closest to term with lowest
      medical risk factors and best neurobehavioral performance.

PMID- 12784904
TI  - Quantitative electroencephalography in OCD patients treated with paroxetine.
AB  - The effectiveness of drugs that have a specific effect on the activity of the
      serotonergic neurotransmitter systemhas changed the outlook for patients
      suffering from obsessive-compulsive disorder (OCD). With a response rate of about
      70% to such compounds and the great amount of brain imaging studies conducted
      over the past decades, an understanding of the biochemical nature and origins of
      OCD is beginning to unfold. Convergent data including ethological and
      experimental observations, clinico-pathological findings and different imaging
      methods have implicated the basal ganglia along with the cortical and related
      thalamic structures to be involved in the pathophysiology of OCD. In a previous
      study using the quantitative electroencephalographic (QEEG) method known as
      neurometrics, in which QEEG data from OCD patients were compared statistically
      with those from an age-appropriate normative population, two subtypes within a
      clinically homogeneous patient group were classified. Patients with relative
      excess theta activity, especially in the frontal regions, were nonresponders to
      treatment with serotonin reuptake inhibitors (SSRI), while those with increased
      relative power in alpha activity were responders to pharmacological treatment.
      These findings suggested at least two subgroups in a patient population with
      similar symptoms but differential responses to treatment. In the present study we
      used neurometric QEEG to subtype a group of 20 non-depressed OCD patients,
      fulfilling DSM-R-III criteria, treated with paroxetine, of whom 18 were
      responders to treatment. Of the treatment responders, 94.4% were predicted by
      subtype membership to be SSRI responsers. In these subjects there was a strong
      relative alpha baseline activity; after successful treatment through at least 3
      months this activity decreased, looking more normal. The group average
      topographic maps showed none of the characteristics seen in the nonresponder
      cluster (no excess relative power in theta). As in the previous investigation,
      baseline QEEG profile membership points to a predictive value with regard to
      therapeutic response.

PMID- 12784905
TI  - Acute marihuana (THC) exposure produces a "transient" topographic quantitative
      EEG profile identical to the "persistent" profile seen in chronic heavy users.
AB  - In two published pilot studies and a controlled replication using screened
      normals, chronic marihuana (THC) use was associated with a unique topographic
      quantitative EEG profile, consisting of significant elevations of Absolute and
      Relative Power and Coherence of alpha activity over the bilateral frontal cortex
      as well as a significant decrease in alpha frequency. This report attempts to
      establish the causal influence of THC in the above findings by the transient
      production of this exact quantitative EEG profile in subjects who did not display
      it at the beginning. Using paced smoking of marihuana with high and low dose THC
      content and placebo marihuana in a counterbalanced design under double blind
      conditions, all four of the topographic features of chronic THC exposure were
      produced as transient effects by THC but not by placebo.

PMID- 12784906
TI  - EEG does not predict response to valproate treatment of aggression in patients
      with borderline and antisocial personality disorders.
AB  - Previous investigations of the role of EEG in predicting response of aggressive
      patients to valproate therapy have yielded mixed results. In this study of
      borderline and antisocial personality disorder patients hospitalized with
      aggressive behavior, EEGs were obtained prior to treatment with valproate. Eight
      of 22 (36.4%) patients subsequently responsive to valproate had nonepileptiform
      EEG abnormalities, while 5 of 20 (25%) patients not responsive to valproate had
      nonepileptiform EEG abnormalities. Although more of the valproate responders than
      nonresponders had EEG abnormalities, the presence of nonepileptiform EEG
      abnormalities was not a statistically significant (X2 = 0.213, df = 1, p = 0.64)
      predictor of valproate response in personality disorder patients with aggression.

PMID- 12784907
TI  - Quantitative EEG effects of topiramate.
AB  - OBJECTIVE: The study is to invesigate the effect of topiramate (TPM) on EEG by
      means of quantitative pharmacoelectroencephalography (QPEEG). METHODS: One dose
      of TPM was administrated to epileptics and healthy adults. The EEG samples were
      obtained prior to and at regular intervals within the 24 hours following the
      administration of TPM. The EEG activity was processed with power spectral
      analysis. RESULTS: The power of slow wave, alpha 1 bands and total power
      increased after the administration of TPM, the power or slow wave in both
      occipital areas, and the total power of all scalp areas also increased. The
      percent of power increased at the theta band and alpha 1 band (healthy adults) or
      delta band, theta band (patients). CONCLUSION: TPM can change the EEG background
      activity. These changes are different from other antiepileptic drugs.

PMID- 12784908
TI  - Comparison of plasma levels of cytokines and in vitro generation of reactive
      oxygen species after nicotine infusion in nicotine users with normal and impaired
      renal function.
AB  - Several in vitro and animal studies suggest effects of nicotine on the immune
      system, but little evidence exists regarding the in vivo immunomodulation of
      nicotine in humans. The increased use of nicotine replacement therapy to aid
      smoking cessation claims further understanding of how nicotine affects blood
      leukocytes. This is of particular importance when nicotine therapy is used in
      diseases associated with alterations of the immune system, such as chronic renal
      failure. The present study evaluates the acute effects of nicotine infusion (NI)
      on some immunoregulatory functions in seven healthy subjects and seven patients
      with renal failure. All subjects were nicotine users and had refrained from using
      nicotine for 36 h before NI. Blood was collected before, immediately after, and 2
      h after NI. Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1)
      and the cytokines interleukin-2 (IL-2), IL-4, IL-10, interferon-gamma and RANTES
      were measured using specific immunoassays. The generation of reactive oxygen
      species (ROS) induced by formyl-methionyl-leucyl-phenylalanine (fMLP),
      Ristocetin, adenosine 5'-diphosphate, or collagen was registered in whole blood
      as luminol-dependent chemiluminescence. Except for fMLP, these compounds induce
      leukocyte ROS generation by platelet mediated mechanisms. NI did not
      significantly affect the levels of the cytokines and ICAM-1 in any group. The
      peak and the persistent ROS production, induced by collagen and Ristocetin, was
      lower at some time points in patients with renal failure as compared to healthy
      subjects. Also in patients with renal failure, both peak height and persistent
      ROS generation induced by Ristocetin were reduced immediately after NI. Thus,
      nicotine inhibits some of the platelet-mediated activation of leukocyte ROS
      generation, and may be associated with platelet defects in renal failure.

PMID- 12784909
TI  - Inhibition of CCL11, CCL24, and CCL26-induced degranulation in HL-60 eosinophilic
      cells by specific inhibitors of MEK1/MEK2, p38 MAP kinase, and PI 3-kinase.
AB  - Eosinophilic leukocytes are the cellular hallmark of allergic inflammation. Apart
      from being potent eosinophils chemoattractants, the eotaxins CCL11, CCL24 and
      CCL26 are capable of activating eosinophils to generate reactive oxygen species,
      lipid mediators of inflammation and degranulation of toxic granule proteins. Due
      to their central role in eosinophil trafficking and activation, understanding the
      signal transduction mechanism of the eotaxin-induced eosinophil effector
      functions may provide an innovative therapeutic strategy for eosinophil
      associated diseases. Thus, these investigations were conducted to delineate
      signal transduction mechanisms of CCL11, CCL24 and CCL26-induced eosinophil
      peroxidase (EPO) degranulation following pretreatment of cells with or without a
      specific inhibitor of MEK1/MEK2 (U0126), inhibitor of p38 MAP kinase (SB203580)
      or a specific inhibitor of PI 3-kinase (LY294002). Results have shown that CCR3
      mediated eotaxin-induced eosinophilic degranulation was concentration-dependently
      reduced by specific inhibitors of ERK1/ERK2, p38 MAP kinase and PI 3-kinase.
      However, the rank order of U0126 with respect to inhibition of chemokine-induced
      degranulation was CCL11 = CCL24 > CCL26. Potentiation of eotaxin-induced EPO
      degranulation by IL-5 was also seen. These investigations have not only confirmed
      the reported co-operativity between IL-5 and the eotaxins but also showed that
      the eosinophil-degranulating capabilities of the eotaxin CCL11, CCL24 and CCL26
      is a consequence of activation of ERK1/ERK2, p38 MAP kinase and PI 3-kinase.
      Thus, these signaling molecules may provide the biochemical basis for mechanism
      based therapy of allergic inflammatory diseases.

PMID- 12784910
TI  - The inhibition of superoxide production in EL4 lymphoma cells overexpressing
      growth hormone.
AB  - A substantial body of research exists to support the production of growth hormone
      by cells of the immune system. However, the function and mechanism of action of
      lymphocyte-derived growth hormone remain largely unelucidated. Since, it has been
      found that exogenous growth hormone (GH) primes neutrophils for the production of
      reactive oxygen intermediates (ROI) and in particular superoxide (O2-), we
      investigated the role of GH on the production of O2- in T cells. Furthermore, we
      examined whether endogenous and exogenous GH act similarly. Our studies show that
      overexpression of GH in EL4, a T-cell lymphoma cell line, results in a decrease
      in the production of O2- compared to control cells, as detected using the
      fluorescent dye, dihydroethidium. O2- production in control cells was not
      affected by treatment with inhibitors of xanthine oxidase or a non-specific NADPH
      oxidase inhibitor. However, treatment with diallyl sulfide, an inhibitor of
      cytochrome P450 2E1 mimicked the reduction in O2- production seen in cells
      overexpressing GH. Although no significant change could be detected in CYP2E1
      protein levels, CYP2E1 activity was found to be greater in control EL4 than in
      cells overexpressing GH. Both the decrease in O2- production and the lower CYP2E1
      activity in GH overexpressing cells could be abrogated by treatment with N(G)
      monomethyl-L-arginine, an inhibitor of nitric oxide synthase. The overexpression
      of GH protects cells from apoptosis induced by isoniazid, a CYP2E1 inducer,
      suggesting a role for nitric oxide as a mediator in the regulation of xenobiotic
      metabolism and apoptosis-protection by lymphocyte GH.

PMID- 12784911
TI  - Adhesion molecules in gonarthrosis and knee prosthesis aseptic loosening follow
      up: possible therapeutic implications.
AB  - The involvement of the synovium is common in phlogistic processes of various
      joint diseases. Apart from synoviocytes and the other cells in the synovial
      tissue, circulating cells recruited from peripheral blood also participate in the
      phlogistic process. The increased expression of adhesion molecules on both
      circulating and endothelial cell surface may further this recruitment. We studied
      15 patients affected by serious gonarthrosis requiring a prosthetic implant (GPI)
      and 7 with knee prosthesis aseptic loosening (KPL) to evaluate adhesion molecule
      expression and phlogistic infiltration in the synovium using immunohistochemistry
      and microscopic analysis. As control we studied 10 subjects affected by
      degenerative meniscopathies undergoing a selective arthroscopic surgical
      meniscectomy. Analysis with Kruskal-Wallis test showed no statistical significant
      differences in the expression of CD54, CD11a, CD11b and CD18 in three groups
      examined. The model of variance analysis (Friedman test), showed that CD54
      expression is greater in patients with GPI and KPL in comparison with the other
      molecules. Adhesion molecules and their functions are important in arthropathies
      not only because their evaluation can allow us to identify the degree of
      inflammation and to predict its evolution, but also because pharmacological
      control of their expression could have important therapeutic implications.

PMID- 12784912
TI  - Bombycis corpus extract (BCE) protects hippocampal neurons against excitatory
      amino acid-induced neurotoxicity.
AB  - Bombycis corpus (BC) or Bombyx Batryticatus, a batryticated silkworm and white
      stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori
      L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In a
      previous paper (Kim et al., Pharmacol. Res., 43, 12-16, 2001), BC was shown to
      protect amyloid-beta-induced cytotoxicity. In the present study, we have found
      that BCE can prevent or reduce the neurotoxic actions in the hippocampus of the
      glutamate agonists N-methyl-D-aspartic acid (NMDA) in vitro or alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid in vitro. Pre
      treatment with BCE (0, 1, 2, 5, and 10 microg/ml for 6-8 h) protected primary
      hippocampal cultures from embryonic day 18 (E18) embryos against NMDA-induced
      toxicity (0.1, 1, 10, and 50 nM/ml). BCE added either with NMDA (1 mM) or 1 h
      later had lesser, but still significant, protective actions. BCE also reduced
      NMDA-induced toxicity (1 mM). BCE (10 microg/ml) protected cultured neurons
      against the neurotoxic actions of either AMPA (25 microM) or kainic acid (1 mM)
      as well. Because the release of glutamate has been implicated in the neural
      damage after cerebral ischemia and other neural insults, these results suggest
      that BCE may contribute significantly to protect human brain to such damage.

PMID- 12784913
TI  - Tumor necrosis factor alpha and apoptosis in Helicobacter pylori related
      progressive gastric damage: a possible mechanism of immune system involvement in
      epithelial turnover regulation.
AB  - Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis
      factor alpha (TNFalpha), which "in vitro" increases epithelial apoptosis in
      response to infection. In the early stages of HP gastritis, a raised epithelial
      apoptosis occurs; this phenomenon becomes less evident with progression towards
      intestinal metaplasia. Aim of our study was to analyze "in vivo" mucosal TNFalpha
      in relation to epithelial apoptosis in the progression of HP related histological
      damage. Antral biopsies from 20 HP positive patients were retrospectively
      studied: 10 with and 10 without intestinal metaplasia (IM and CG group
      respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were
      used as control. The following parameters were evaluated by immunohistochemistry:
      85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase
      (PARP) labelling index (LI) as marker of apoptosis and TNFalpha LI in stromal
      cells as marker of inflammatory response. Both epithelial apoptosis and mucosal
      TNFalpha expression were higher in chronic active gastritis compared to
      intestinal metaplasia and controls (PARP and TNFalpha LI: CG > IM > N; ANOVA &
      Student-Neumann-Keuls; p < 0.05 and p < 0.01, respectively). Pearson's
      coefficient showed a significant correlation between PARP and TNFalpha LI in IM
      and CG groups. Our data show that mucosal TNFalpha, similarly to what suggested
      "in vitro", may be related "in vivo" to epithelial apoptosis thus suggesting a
      possible mechanism for immune system involvement in the control of gastric
      epithelial turnover.

PMID- 12784914
TI  - Modulation of inflammatory mediators by ibuprofen and curcumin treatment during
      chronic inflammation in rat.
AB  - Inflammation is a protective tissue response occurring in three distinct phases,
      acute, subacute and a chronic proliferative phase. We undertook the present study
      to understand the overall immune response of the body during adjuvant induced
      chronic inflammation in rat and the effect of ibuprofen and curcumin on this
      response. Inflammatory mediators were estimated on day 21 and day 35 after
      adjuvant injection. The level of C-reactive protein increased to 200% on day 21
      and then reduced to 50% on day 35 compared to control. Curcumin and ibuprofen
      further reduced the increased levels at both the time intervals. Haptoglobin
      level decreased to 42% on day 21 but increased to 5 times of control on day 35.
      Curcumin and ibuprofen reduced the increased levels at day 35. No significant
      change was observed in Prostaglandin-E2 and Leukotriene-B4 levels and in
      Lymphocyte proliferation. The level of Tumor Necrosis Factor-alpha increased by
      three folds on day 21, but came down to 88% on day 35. Ibuprofen treatment
      decreased the raised level on day 21 and increased the reduced level on day 35.
      Interleukin-1beta increased to 2 folds on day 21 and 10 folds on day 35 which
      were significantly brought down by curcumin and ibuprofen. Nitric oxide level was
      reduced at both the time intervals, which were increased by drug treatment.

PMID- 12784915
TI  - Inhibition of anti-CD3 and interleukin-2 stimulated T lymphocyte proliferation by
      peptidomimetic opioid compound.
AB  - In continuation to our earlier studies with peptidomimetic opioid compounds, we
      have further investigated immunosuppressive properties of one of our
      peptidomimetic compound (Tyr-NH-CH2-CH2-O-Phe-NH2) using peripheral blood
      mononuclear cells (PBMCs) of healthy volunteers. Peptidomimetic compound was
      evaluated for its effect on anti-CD3 and recombinant human interleukin-2 (rhIL-2)
      stimulated lymphocyte proliferation in vitro and lipopolysaccharide (LPS) induced
      activation of mitogen activated protein kinase (MAPK, pp42/44) in mouse
      macrophage cells (RAW 264.7). Our results show the immunosuppressive potential of
      synthetic peptidomimetic compound. This compound significantly inhibited anti-CD3
      and rhIL-2 stimulated lymphocyte proliferation in vitro. However, this
      peptidomimetic compound did not show any effect on LPS induced MAPK activation.
      These observations suggest that above peptidomimetic compound has potential to
      inhibit immune responses mediated by lymphocytes.

PMID- 12784916
TI  - Minimal effects on immune parameters following chronic anti-TGF-beta monoclonal
      antibody administration to normal mice.
AB  - Mice genetically deficient in TGF-beta1 or TGF-beta signaling capacity in T or B
      cells demonstrate profound immune dysregulation, as evidenced by increased lymph
      node size, expression of markers of memory/activation on T cells, inflammation in
      a variety of tissues and development of autoantibodies. However, this constant
      and complete lack of TGF-beta1 or TGF-betaR signaling may not reflect effects of
      TGF-beta neutralization using antibodies in mature animals. Thus, the present
      studies were designed to determine if administration of an anti-TGF-beta
      monoclonal antibody (neutralizes TGF-beta1, 2 and 3) to mature, normal mice
      results in evidence of immune dysregulation or immune-mediated pathology. An
      initial study examined daily administration of 0.25, 0.75 and 2.5 mg/kg of anti
      TGF-beta to mice for three weeks, achieving blood levels of as high as 9 mg/ml.
      Comprehensive hematological and histopathological evaluation showed no evidence
      of pathology. A second study was designed to extend the antibody treatment period
      and further examine the functional status of the immune system. Mice were
      injected with 1 mg/mouse (approximately 50 mg/kg) of anti-TGF-beta (1D11) three
      times per week achieving circulating blood levels of 1-2 mg/ml. Many parameters
      of immune status were assessed, including natural killer (NK) cell activity,
      lymphocyte proliferative responses, phagocytic activity, phenotypic assessment of
      leukocyte subsets, and serum measurements of proinflammatory cytokines,
      autoantibodies and immunoglobulin isotypes. In addition, histopathological
      assessment of heart, lungs, liver, kidney, salivary glands, skin, spleen and
      lymph nodes was also performed. Very few of the multiple immune parameters
      examined showed detectable changes in anti-TGF-beta-treated mice. Changes that
      were observed were primarily restricted to the spleen and included increased
      spleen cell recoveries, increased percentages of macrophages, decreased
      percentages of NK cells, decreased phagocytic activity, decreased proliferative
      responses to mitogens and slight increases in T and B cells displaying an
      activated phenotype. Many of these same parameters examined in the lymph nodes
      were not altered by the anti-TGF-beta treatment. The thymus was decreased in
      size, but altered only slightly in one population of developing T cells. Most of
      the changes observed were modest and returned to control levels after
      discontinuation of treatments. The only serological finding was an increase in
      IgA levels in anti-TGF-beta-treated mice, but not in any other isotype. Finally,
      there was no evidence of increased inflammation in any of the peripheral tissues
      examined in the anti-TGF-beta-treated mice. In conclusion, although there were
      changes in some of the immunological parameters examined in these studies, they
      were few and typically reversed following discontinuation of treatment. The
      modest nature of the changes observed in these studies is particularly evident
      when compared to published data of those same parameters examined in mice
      genetically deficient in TGF-beta1 or mice having TGF-beta unresponsive T or B
      cells. Thus, there does not appear to be any significant immune dysregulation
      detectable after long-term antibody-mediated neutralization of TGF-beta in normal
      mice.

PMID- 12784917
TI  - Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice.
AB  - Dang-Gui-Bu-Xai-Tang (DGBXT), which includes Radix Angelicae Sinensis and Radix
      Astragali Membranaceus, is a traditional Chinese medicine used to modulate the
      lymphocyte activity of cancer patients after chemotherapy and radiotherapy. In
      the present study, we examined the cytotoxicity of DGBXT on transformed cells and
      the immunomodulating effects of DGBXT in a tumor-bearing murine model. DGBXT
      markedly inhibited the growth of the EJ-Ha-ras transformed LZEJ and LZEJ-C2 cells
      lines. Oral administration of DGBXT for three weeks significantly prevented the
      tumor development in mice that injected with LZEJ-C2 cells subcutaneously.
      Moreover, DGBXT effectively increased the population of cytotoxic T lymphocytes
      (CTLs) and NK cells, and down-regulated activated T helper cells (CD4+/CD25+) in
      spleen and tumor-draining lymph nodes (TDLN). Furthermore, DGBXT stimulated the
      production of tumor necrosis factor-alpha in in vitro cultured splenocytes. These
      results might explain the antitumor effects of DGBXT.

PMID- 12784918
TI  - Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic
      reactions by the aqueous extract of Mentha arvensis.
AB  - The effect of aqueous extract of Mentha arvensis L. var. piperascens Malinv.
      (Labiatae) (MAAE) on immunologic and nonimmunologic stimulation-mediated
      anaphylactic reactions was studied. Nonimmunologic anaphylactic reaction was
      induced by compound 48/80 injection. MAAE (0.005 to 0.5 g/kg) inhibited systemic
      anaphylactic reaction induced by compound 48/80. Immunologic anaphylactic
      reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE
      followed 48 h later with an injection of antigen. MAAE (0.001 to 1 g/kg) dose
      dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally,
      intraveneously and orally administered. MAAE (0.001 to 1 mg/ml) dose-dependently
      inhibited the histamine release from rat peritoneal mast cells (RPMC) activated
      by compound 48/80 or anti-DNP IgE. Moreover, MAAE (0.1 mg/ml) had a significant
      inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-alpha (TNF
      alpha) production. These results indicate that MAAE inhibits immunologic and
      nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha
      production from RPMC.

PMID- 12784919
TI  - Immunomodulatory activity of naturally occurring monoterpenes carvone, limonene,
      and perillic acid.
AB  - The immunomodulatory activity of some naturally occurring monoterpenes were
      studied in Balb/c mice. Administration of various monoterpenes such as carvone
      (100 micromoles/Kg body wt/dose/animal), limonene (100 micromoles/Kg body
      wt/dose/animal) and perillic acid (50 micromoles/Kg body wt/dose/animal) were
      found to increase the total white blood cells (WBC) count in Balb/c mice. The
      maximum total WBC count in carvone treated animals was observed on the 12th day
      (16,560 cells/cmm) while in limonene (13,783 cells/cmm) and perillic acid (14,437
      cells/cmm) treated animals the maximum count was observed on the 9th day after
      the drug treatment. Administration of terpenoids increased the total antibody
      production, antibody producing cells in spleen, bone marrow cellularity and alpha
      esterase positive cells significantly compared to the normal animals indicating
      its potentiating effect on the immune system.

PMID- 12784920
TI  - Revocation of tax-exempt status, excise taxes, and other intermediate sanctions
      issues, plus income taxes: how the rules have changed after Caracci v.
      Commissioner.
AB  - This Article discusses Caracci v. Commissioner, in which the Tax Court imposed
      intermediate sanctions based on its finding that insiders caused three applicable
      tax-exempt organizations to sell assets to three for-profit entities owned and
      controlled by those same insiders. It explores the standards enumerated in
      Caracci, hypothesizes as to the pending appeal, and examines the guidance given
      by the decision's clarification of the intermediate sanctions provisions of the
      Internal Revenue Code.

PMID- 12784921
TI  - Tax-exempt bonds and sponsored research.
AB  - "Sponsored research," wherein a business corporation or the government pays a
      portion of the cost of research activities carried out by a university or
      hospital, is increasingly important both for state institutions and for Section
      510(c)(3) organizations. Sponsored research arrangements that are not properly
      structured can jeopardize the status of tax-exempt bonds issued to finance the
      facility at which the sponsored research occurs. While these rules have been
      difficult to apply in practice, properly structured agreements can provide
      funding for research without undue risk. This Article discusses the multiple
      pieces of guidance put forth by the Internal Revenue Service to clarify the many
      issues and tiers of analysis necessary to ensure a properly-structured sponsored
      research agreement.

PMID- 12784922
TI  - The ongoing debate over Medicare: understanding the philosophical and policy
      divides.
AB  - This Article examines the evolution and status of Medicare, as well as the myriad
      current efforts to reform this longstanding entitlement. The author analyzes why
      healthcare financing for the elderly follows an administered pricing, fee-for
      service model, while the working population generally obtains its insurance under
      a competitive market model. As a non-means-tested program modeled after Social
      Security, Medicare embraces both a universal entitlement philosophy of government
      provided basic health services, and a need-based entitlement philosophy of caring
      for the Medicare-eligible elderly.

PMID- 12784923
TI  - The impact of the recent Supreme Court rulings in Pegram and Rush Prudential on
      state regulation of managed care organizations.
AB  - Over the past two decades, the Employee Retirement Income Security Act of 1974
      (ERISA) has shielded managed care organizations (MCOs) from liability for
      negligent treatment or coverage decisions. This Article examines the Supreme
      Court jurisprudence in the area of ERISA preemption, and assesses the impact of
      these recent decisions on state regulation of MCOs. The author concludes that
      recent decisions in Pegram v. Herdrich and Rush Prudential HMO, Inc. v. Moran
      have broadened the states' power to regulate MCOs and enhance the ability of
      injured plaintiffs to sue such organizations under state tort law.

PMID- 12784924
TI  - Federal Trade Commission v. Tenet: a retrospective review and analysis.
AB  - Primarily through a series of interviews with a variety of interested persons,
      the author analyzes the controversial merger of two hospitals in Poplar Bluff,
      Missouri, in late 1999. A district court had stopped the merger in 1998; however,
      the Eighth Circuit overturned the decision the following year, therefore
      permitting the parties to execute the merger. The Article highlights the effects
      of, and the market's response to, the merger. Results reveal that in the two
      years following the merger, none of the parties interviewed believe the merger
      was favorable. Similarly, parties perceive that the price of care has increased,
      while the quality of care has not improved. Nonetheless, at the two-year mark, it
      remains too soon to determine whether the government's concerns in opposing the
      merger have been justified.

PMID- 12784925
TI  - Intermediate sanctions flow charts.
AB  - In this Article, the author presents and explains two flow charts that facilitate
      the analysis of the intermediate sanctions provisions. The first chart guides one
      in determining whether a particular transaction is subject to the sanctions. The
      second assists in calculating the monetary amount of any applicable sanction.

PMID- 12784926
TI  - Neuroprotective effect of ACTH (4-9) in degeneration of hippocampal nerve cells
      caused by dexamethasone: morphological, immunocytochemical and ultrastructural
      studies.
AB  - Sustained exposure to glucocorticosteroids (GCs), adrenal hormones secreted
      during stress, can cause neural degeneration. This is particularly so in the
      hippocampus, a principal neural target site for GCs. The purpose of this research
      was an assessment of the neuroprotective effect of ACTH (4-9) in degenerative
      changes of hippocampal neurons induced by synthetic GC-dexamethasone. Experiments
      were conducted on male Albino-Swiss mice. We studied the morphology of neurons in
      the dorsal hippocampus in slides stained with cresyl violet. Immunocytochemical
      analysis was carried out with the use of monoclonal antibody anti-MAP2 in order
      to detect alterations in the neuronal cytoskeleton. We also performed
      ultrastructural examinations of hippocampal neurons. Quantitative analysis of
      morphological changes was completed using a computer analyser of histological
      pictures. It was shown that dexamethasone administered in toxic doses evokes
      neuronal death in layer CA3 of the hippocampus. Results indicate that ACTH (4-9)
      shows protective effects in that model. Dexamethasone-induced damage to
      hippocampal pyramidal neurons (assessed by cell counts, immunocytochemical
      analysis of cytoskeletal alterations and ultrastructural studies) was
      significantly reduced in animals administered ACTH (4-9).

PMID- 12784927
TI  - Effects of infusion of corticotropin-releasing factor antagonist into the locus
      coeruleus on freezing behavior and brain catecholamines in rats.
AB  - Administration of 0.2 microg of alpha-helical CRF(9-41) (corticotropin-releasing
      factor receptor antagonist, ahCRF(9-41)) into the locus coeruleus (LC) region
      significantly reduced footshock-induced freezing behavior in adult male rats.
      Changes in the concentrations of noradrenaline (NA), dopamine and their
      catabolites in cortex, hippocampus and hypothalamus of footshocked rats were
      reminiscent of those observed in stressed animals. Rats injected with ahCRF prior
      to footshock displayed cerebral catecholamine responses that were not different
      from controls injected with vehicle. The results confirm earlier findings that
      CRF receptors at the LC region may mediate freezing and behavioral expression of
      fear. However, the results also suggest that though CRF receptors within the LC
      region mediate footshock-induced behavior, they are not necessarily involved in
      the short-term catecholamine response to footshock.

PMID- 12784928
TI  - Individual variation in the spatial reference and working memory assessed under
      allothetic and idiothetic orientation cues in rat.
AB  - The present study was designed to examine which kind of memory: reference or
      working, better correlates with individual variation in rats' spatial learning
      abilities. To answer this question two groups of rats were trained to an
      arbitrary criterion in a partially baited 12-arm radial maze under two different
      experimental conditions: with or without allothetic cues. After 10 days break,
      rats were examined under the same conditions for memory retention. Within- and
      between-group variation in the length of training to criterion, and in the
      frequency of reference and working memory errors were analysed. The present
      experiment confirmed the facilitating effect of the presence of distal visual
      cues on place learning in rats. Task-dependent (between-group) differences in the
      rate of learning were attributed to differences in the frequency of reference
      memory errors. Conversely, within-group variation in the rate of task acquisition
      reflected individual variation in the frequency of working memory errors. These
      results were looked upon from an evolutionary perspective. Low correlation
      between reference and working memory errors confirms that these two types of
      memory have different mechanisms. The fact that differences in the rate of
      learning were not paralleled by the differences in the memory retention supports
      the notion that memory acquisition and memory retention are two independent
      processes.

PMID- 12784929
TI  - Startle response to short acoustic stimuli in rats.
AB  - The acoustic startle (ASR) is a transient motor response to an unexpected,
      intensive stimulus. The response is determined by stimulus parameters such as its
      intensity, rise time and duration. The dependence of the ASR on the stimulus
      duration is more complex than could be assumed from physical properties of
      acoustic pulse. This effect attracted the attention of few researchers. Some
      authors reported noticeable changes in the ASR amplitude only for very short
      (less than 4-6 ms) acoustic pulses. The systematic studies on the effect,
      however, have not been performed so far. The purpose of this study was to
      determine to what extent the ASR parameters are affected by the durations of the
      short stimulus. The amplitude of the acoustic startle reflex was assessed for a
      fixed tonal frequency (6.9 kHz), and for a variety of stimulus durations ranging
      between 2 and 10 ms. ASRs were studied in 11 adult, hooded rats exposed to a
      sequence of tone pulses (110 dB SPL) of different durations, presented in random
      order, with or without 70 dB white noise as a background. Statistical analysis
      revealed significant differences between ASR amplitudes for different durations.
      The startle amplitude increased with acoustic pulse duration and distinguishable
      differences were seen for stimulus duration between 2 and 8 ms. Further increase
      of pulse duration had no effect on ASR amplitude. The same pattern of changes was
      observed when the acoustic stimulus was presented with the white noise. In the
      tested range of stimulus duration no significant differences in the ASR latency
      were found. The observed differences may be attributed to changes of stimulus
      acoustic energy and to physiological characteristic of auditory system in the
      rat.

PMID- 12784930
TI  - Memory for object and object-location after lesions to the ventromedial
      prefrontal cortex in humans.
AB  - The aim of the present study was to investigate the effect of small unilateral
      lesions to the ventromedial portion of the prefrontal cortex on two memory
      functions: memory for objects and memory for object locations. Patients, who had
      undergone surgery of the anterior communicating artery aneurysm, and normal
      control subjects, participated in the study. The patients were subdivided into
      two groups: with and without unilateral resection of the gyrus rectus. Subjects
      were presented with two memory tests, that required remembering either
      simultaneously presented visual stimuli (object memory test; OMT) or locations of
      the stimuli (location memory test; LMT). In the OMT, patients with resection of
      the gyrus rectus were impaired in comparison to patients without resection and
      normal control subjects. In the LMT, the three groups did not differ from each
      other. Our results suggest that the ventromedial prefrontal cortex is
      specifically involved in memory for objects.

PMID- 12784931
TI  - Central control of heart rate changes during visual affective processing as
      revealed by fMRI.
AB  - In the present study we addressed the question of central control of heart rate
      (HR) in emotions. Parallel measurement of HR changes and changes of local
      intensity of blood flow as indexed by fMRI in a procedure eliciting emotions
      allowed us to pinpoint areas of the brain responsible for HR variations during
      emotional arousal. In condition eliciting positive emotions we detected
      activation of occipito-temporal regions, anterior insula, and hypothalamus. In
      condition eliciting negative emotions we also detected activation of occipito
      temporal regions and additionally activation of bilateral anterior insulae, right
      amygdala and right superior temporal gyrus. The results show that structures
      constituting neural network involved in HR control during emotional arousal are
      affect specific. Particularly the central circuit controlling HR in negative
      affect includes the amygdala, while central circuit controlling HR in positive
      affect includes the hypothalamus. Additionally activation of bilateral occipito
      temporal cortex proves enhancement of visual processing of emotional material as
      compared to neutral material in both positive and negative affect. This might be
      attributed to top-down processes originating in the frontal lobe and related to
      shifting attention to the emotionally relevant stimuli. Activation of insular
      cortex is probably related to autonomic arousal accompanying watching emotional
      content (e.g. sweating, heart-rate changes etc.). Activation of the amygdala in
      the negative condition supports the well documented engagement of this structure
      in processing of fear and disgust.

PMID- 12784932
TI  - Combined measurement of event-related potentials (ERPs) and fMRI.
AB  - The study investigates the possibility of combined recording event-related
      potentials (ERPs) and functional MRI (fMRI). Visual evoked potentials (VEPs) were
      elicited by an alternating black and white checkerboard, which was presented
      blockwise outside the static 1.5 T magnetic field and during an echo planar
      imaging (EPI). An fMRI sequence with a time window for interleaved EEG
      measurement and a measurement protocol which reduces pulse artifacts and
      vibrations was used. Thus, during an EPI sequence, it was possible to detect VEPs
      which had the same structure and latencies as VEPs outside the magnetic field and
      which corresponded well with the observed activated areas of the visual cortex.

PMID- 12784933
TI  - Event-related potentials--the P3 wave.
AB  - Event-Related Potentials (ERPs) are a basic, non-invasive method of
      neurophysiological investigation. They can be used to assess aspects of human
      cognitive information processing. They also can be used in experiments on higher
      mammals. The most important and the most studied component of the ERP record is
      the P3 wave. It consists of two parts, P3a and P3b. There is no doubt that,
      besides the use in neurophysiological and psychophysiological research, the P3
      wave also has clinical importance. Changes in its latency, amplitude and
      topography are correlated with clinical findings in a wide range of different
      ailments. The mini-review we present summarises the current state of the P3 wave
      research in experimental and clinical studies.

PMID- 12784934
TI  - Political conservatism as motivated social cognition.
AB  - Analyzing political conservatism as motivated social cognition integrates
      theories of personality (authoritarianism, dogmatism-intolerance of ambiguity),
      epistemic and existential needs (for closure, regulatory focus, terror
      management), and ideological rationalization (social dominance, system
      justification). A meta-analysis (88 samples, 12 countries, 22,818 cases) confirms
      that several psychological variables predict political conservatism: death
      anxiety (weighted mean r = .50); system instability (.47); dogmatism-intolerance
      of ambiguity (.34); openness to experience (-.32); uncertainty tolerance (-.27);
      needs for order, structure, and closure (.26); integrative complexity (-.20);
      fear of threat and loss (.18); and self-esteem (-.09). The core ideology of
      conservatism stresses resistance to change and justification of inequality and is
      motivated by needs that vary situationally and dispositionally to manage
      uncertainty and threat.

PMID- 12784935
TI  - Psychological motives and political orientation--the left, the right, and the
      rigid: comment on Jost et al. (2003).
AB  - Presenting an impressive model based on a large body of evidence, J. T. Jost, J.
      Glaser, A.W. Kruglanski, and F. J. Sulloway (2003) proposed that political
      conservatism uniquely serves epistemic, existential, and ideological needs driven
      by fears and uncertainties. The authors offer an alternative view based on
      conceptual considerations, historical events, features of communist ideology and
      practice, and additional social science research not reviewed by Jost et al.
      (2003). First, the authors take issue with Jost et al.'s (2003) description of
      the two core components of political conservatism. Second, they propose that the
      motives in the model are equally well served by rigid adherence to any extreme
      ideology regardless of whether it is right wing or left wing.

PMID- 12784936
TI  - A review of the deja vu experience.
AB  - For more than a century, the deja vu experience has been examined through
      retrospective surveys, prospective surveys, and case studies. About 60% of the
      population has experienced deja vu, and its frequency decreases with age. Deja vu
      appears to be associated with stress and fatigue, and it shows a positive
      relationship with socioeconomic level and education. Scientific explanations of
      deja vu fall into 4 categories: dual processing (2 cognitive processes
      momentarily out of synchrony), neurological (seizure, disruption in neuronal
      transmission), memory (implicit familiarity of unrecognized stimuli),and
      attentional (unattended perception followed by attended perception). Systematic
      research is needed on the prevalence and etiology of this culturally familiar
      cognitive experience, and several laboratory models may help clarify this
      illusion of recognition.

PMID- 12784937
TI  - A justification-suppression model of the expression and experience of prejudice.
AB  - The authors propose a justification-suppression model (JSM), which characterizes
      the processes that lead to prejudice expression and the experience of one's own
      prejudice. They suggest that "genuine" prejudices are not directly expressed but
      are restrained by beliefs, values, and norms that suppress them. Prejudices are
      expressed when justifications (e.g., attributions, ideologies, stereotypes)
      release suppressed prejudices. The same process accounts for which prejudices are
      accepted into the self-concept The JSM is used to organize the prejudice
      literature, and many empirical findings are recharacterized as factors affecting
      suppression or justification, rather than directly affecting genuine prejudice.
      The authors discuss the implications of the JSM for several topics, including
      prejudice measurement, ambivalence, and the distinction between prejudice and its
      expression.

PMID- 12784938
TI  - Stressors and child and adolescent psychopathology: moving from markers to
      mechanisms of risk.
AB  - In the first half of this review, the authors critically evaluate existing
      research on the association between stressors and symptoms of psychopathology in
      children and adolescents. This analysis reveals (a) problems with
      conceptualizations of stress, (b) variability in measurement of stressors, and
      (c) lack of theory-driven research. To address these problems, the authors
      propose a general conceptual model of the relation between stressors and child
      and adolescent psychopathology. The authors examine basic tenets of this general
      model in the second half of this article by testing a specific model in which
      negative parenting mediates the relation between economic stressors and
      psychological symptoms in young people. Results generally provide support for the
      specific model as well as for the broader model.

PMID- 12784940
TI  - AAHA study finds millions of pets aren't getting maximum health care.

PMID- 12784939
TI  - Identifying a killer: SARS virus.

PMID- 12784941
TI  - Canine vaccination guidelines intended for individualized treatment.

PMID- 12784942
TI  - AVMA president calls for veterinarians to be more visibly engaged in ensuring
      welfare of entertainment animals.

PMID- 12784943
TI  - Heightened security precautions may cause problems for horse transportation.

PMID- 12784944
TI  - Think screening unnecessary, unrealistic for all blood donors.

PMID- 12784945
TI  - Common method for pain perception may be inappropriate.

PMID- 12784946
TI  - Support for reevaluation of veterinary science research.

PMID- 12784947
TI  - Urges discussion on financial responsibility.

PMID- 12784948
TI  - Believes cat declawing has positive implications.

PMID- 12784949
TI  - A call for change in veterinary terminology.

PMID- 12784950
TI  - Wants stand on animal-friendly farming.

PMID- 12784951
TI  - Critical anthropomorphic evaluation and treatment of postoperative pain in rats
      and mice.

PMID- 12784952
TI  - Renewed directions in veterinary medical education.

PMID- 12784953
TI  - What is your diagnosis? Bone lysis and sclerosis of the vertebral end plates and
      narrowing of intervertebral disk spaces T5-6, T7-8, L2-3, L3-4, and L5-6.

PMID- 12784954
TI  - Initial study results on future needs for leadership in veterinary medicine.

PMID- 12784955
TI  - Importance of appropriate amounts of magnesium in rations for dairy cows.

PMID- 12784956
TI  - Results of the 2002 AVMA survey of US pet-owning households regarding use of
      veterinary services and expenditures.

PMID- 12784957
TI  - Separation anxiety syndrome in dogs and cats.

PMID- 12784958
TI  - Avian influenza and Newcastle disease.

PMID- 12784959
TI  - Evaluation of cat and owner characteristics and their relationships to outdoor
      access of owned cats.
AB  - OBJECTIVE: To examine characteristics of cats and their owners with regard to
      outdoor access of owned cats. DESIGN: Cross-sectional study. ANIMALS: 184 owned
      cats admitted to a veterinary referral center for nonemergency health concerns.
      RESULTS: Cats acquired recently were less likely to be allowed outdoors than
      those acquired during previous years. Outdoor access was often limited during the
      day; few owners allowed their cats to remain outdoors at night. Cats acquired
      from shelters were more likely to be kept exclusively as indoor pets than those
      cats acquired as strays. The presence of dogs but not other cats in the household
      was associated with increased outdoor access. Age, health status, and onychectomy
      status were not significantly associated with outdoor access. Cats allowed
      outdoor access were more likely to have been bitten by other cats. CONCLUSIONS
      AND CLINICAL RELEVANCE: The basis for an owner's decision to allow outdoor access
      appears to be multifactorial, and there may be regional differences in outdoor
      access of owned cats. Acquisition source is associated with outdoor access of
      owned cats. Availability of information regarding outdoor access of cats may
      influence decision making. Educational efforts targeted at specific groups of cat
      owners, as well as programs that acknowledge owner beliefs regarding quality of
      life for their cats, may help to address the health, safety, and population
      concerns associated with outdoor access of owned cats.

PMID- 12784960
TI  - Efficacy of Giardia vaccination in the treatment of giardiasis in cats.
AB  - OBJECTIVE: To assess efficacy of Giardia vaccination as a treatment for
      giardiasis in experimentally infected cats. DESIGN: Original study. ANIMALS: 16
      young-adult cats. PROCEDURE: Cats were experimentally infected by orogastric
      administration of Giardia cysts. On weeks 4, 6, and 10, cats in the treatment
      group (n = 8) were given Giardia vaccine SC. For the first 28 weeks after
      infection, 3 fecal samples from each cat were examined weekly for Giardia cysts,
      and cyst numbers were counted. Fecal consistency was scored daily for the
      duration of the study. Results from vaccinated and unvaccinated cats were
      compared by logistic regression. RESULTS: All cats became infected and were
      shedding Giardia cysts by the end of week 2. Throughout the study, diarrhea was
      rare and was mild and transient when it did occur. By week 28, 5 of 8 vaccinated
      cats and 7 of 8 control cats had patent Giardia infections. Magnitude of
      infection, based on number of fecal samples with cysts and number of cysts per
      sample, decreased progressively in both groups over time. CONCLUSIONS AND
      CLINICAL RELEVANCE: Administration of 3 doses of a Giardia vaccine did not
      completely eliminate the organism from experimentally infected cats in the study
      period. Since clinical signs were minimal in both groups of cats, it could not be
      determined whether vaccination lessened severity of clinical disease. Results may
      have been negatively influenced by the large inoculation dose. Whether Giardia
      vaccination is an effective treatment for giardiasis in naturally infected cats
      remains to be determined.

PMID- 12784962
TI  - Minimum alveolar concentration of isoflurane in green iguanas and the effect of
      butorphanol on minimum alveolar concentration.
AB  - OBJECTIVE: To determine minimum alveolar concentration (MAC) of isoflurane in
      green iguanas and effects of butorphanol on MAC. DESIGN: Prospective randomized
      trial. ANIMALS: 10 healthy mature iguanas. PROCEDURE: in each iguana, MAC was
      measured 3 times: twice after induction of anesthesia with isoflurane and once
      after induction of anesthesia with isoflurane and IM administration of
      butorphanol (1 mg/kg [0.45 mg/lb]). A blood sample was collected from the tail
      vein for blood-gas analysis at the beginning and end of the anesthetic period.
      The MAC was determined with a standard bracketing technique; an electrical
      current was used as the supramaximal stimulus. Animals were artificially
      ventilated with a ventilator set to deliver a tidal volume of 30 mL/kg (14 mL/lb)
      at a rate of 4 breaths/min. RESULTS: Mean +/- SD MAC values during the 3 trials
      (2 without and 1 with butorphanol) were 2.0 +/- 0.6, 2.1 +/- 0.6, and 1.7 +/-
      0.7%, respectively, which were not significantly different from each other. Heart
      rate and end-tidal partial pressure of CO2 were also not significantly different
      among the 3 trials. Mean +/- SD heart rate was 48 +/- 10 beats/min; mean end
      tidal partial pressure of CO2 was 22 +/- 10 mm Hg. There were no significant
      differences in blood-gas values for samples obtained at the beginning versus the
      end of the anesthetic period. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that the MAC of isoflurane in green iguanas is 2.1% and that butorphanol does not
      have any significant isoflurane-sparing effects.

PMID- 12784961
TI  - Evaluation of methods for assessment of pain associated with chronic
      osteoarthritis in dogs.
AB  - OBJECTIVE: To identify variables and evaluate methods for assessing chronic pain
      in dogs. DESIGN: Prospective study. ANIMALS: 41 dogs with canine hip dysplasia
      (CHD), and 24 apparently healthy dogs with no history of pain. PROCEDURE: 2
      veterinarians evaluated the dogs' locomotion and signs of pain. Owners of dogs
      with CHD and control dogs answered a questionnaire regarding their dogs'
      demeanor, behavior, and locomotion (descriptive scales) and assessed pain and
      locomotion (visual analog scales). Plasma concentrations of several stress
      related hormones were determined, and 13 radiologic variables were assessed in
      affected hip joints. RESULTS: For many of the questions, answers provided by
      owners of dogs with CHD differed significantly from those of owners of control
      dogs. Stress hormone concentrations differed significantly between dogs with CHD
      and controls, but individual variation was too great for them to be of value in
      pain assessment. None of the radiologic variables examined correlated well with
      owner or veterinarian pain scores. CONCLUSIONS AND CLINICAL RELEVANCE: Chronic
      pain could be assessed in dogs with CHD through completion of the study
      questionnaire by a person familiar with the pet (eg, owner) after receiving
      appropriate education in its use. Eleven variables were identified as being
      potentially useful in assessment of chronic pain in dogs.

PMID- 12784963
TI  - The cardiac anesthetic index of isoflurane in green iguanas.
AB  - OBJECTIVE: To determine the cardiac anesthetic index (CAI) of isoflurane in green
      iguanas and whether butorphanol affected the CAI. DESIGN: Prospective randomized
      controlled trial. ANIMALS: 7 healthy mature iguanas. PROCEDURE: In 5 iguanas, CAI
      was determined after induction of anesthesia with isoflurane alone, and in 5
      iguanas, CAI was determined after induction of anesthesia with isoflurane and IM
      administration of butorphanol (1 mg/kg [0.45 mg/lb]). Three iguanas underwent
      both treatments. Animals were equilibrated for 20 minutes at 1.5 times the
      minimum alveolar concentration (MAC) of isoflurane and observed for evidence of
      cardiovascular arrest. If there was no evidence of cardiovascular arrest, end
      tidal isoflurane concentration was increased by 20%, and animals were allowed to
      equilibrate for another 20 minutes. This process was repeated until
      cardiovascular arrest occurred or vaporizer output could no longer be
      consistently increased. The CAI was calculated by dividing the highest end-tidal
      isoflurane concentration by the MAC. RESULTS: None of the iguanas developed
      cardiovascular arrest and all survived. Mean +/- SD highest end-tidal isoflurane
      concentration during anesthesia with isoflurane alone (9.2 +/- 0.60%) was not
      significantly different from mean concentration during anesthesia with isoflurane
      and butorphanol (9.0 +/- 0.43%). The CAI was > 4.32. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that the CAI of isoflurane in green iguanas is > 4.32
      and not affected by administration of butorphanol. Isoflurane appears to be a
      safe anesthetic in green iguanas.

PMID- 12784964
TI  - Use of positive contrast rhinography and intranasal sinography for diagnosis of a
      nasofacial sinus tract in a dog.
AB  - Twelve days after a dog fight, a 2-year-old sexually intact female Bulldog was
      evaluated because of subcutaneous emphysema of increasing severity throughout the
      dogs body. Thoracic radiography revealed severe pneumomediastinum from which free
      air had extended into the retroperitoneal space, resulting in pneumoperitoneum.
      Tracheoscopic examination did not reveal a discontinuity of the trachea, pharynx,
      or larynx. A breach between the nasal cavity and subcutaneous tissues of the
      nasal region was suspected. Further diagnostic investigations included positive
      contrast rhinography and intranasal sinography. Via an angiographic catheter
      inserted into the left naris, positive contrast intranasal sinography revealed a
      sinus tract extending between the left nasal cavity and the subcutaneous tissue
      of the dorsal aspect of the nasal planum. Resolution of subcutaneous emphysema,
      pneumomediastinum, and pneumoretroperitoneum began 1 day after surgical closure
      of the intranasal opening of the sinus tract. To the authors' knowledge, this
      radiographic technique has not been reported.

PMID- 12784965
TI  - Spontaneous pneumothorax in two cats with small airway disease.
AB  - Two adult domestic shorthair cats were examined because of pneumothorax. Neither
      had a history of trauma, and spontaneous pneumothorax secondary to small airway
      disease was diagnosed. In both cats, treatment consisted of thoracocentesis for
      evacuation of air and administration of anti-inflammatory agents. One cat had
      multiple episodes of pneumothorax and eventually died; the other had only a
      single episode of pneumothorax. Small airway disease should be considered as a
      potential underlying cause in cats that develop spontaneous pneumothorax.
      Additionally, the potential for pneumothorax should be considered in cats with
      small airway disease, particularly when clinical signs suddenly become much
      worse.

PMID- 12784966
TI  - Antegrade pyelography for suspected ureteral obstruction in cats: 11 cases (1995
      2001).
AB  - OBJECTIVE: o determine sensitivity and specificity of radiography,
      ultrasonography, and antegrade pyelography for detection of ureteral obstructions
      in cats. DESIGN: Retrospective study. ANIMALS: 11 cats. PROCEDURE: Medical
      records of cats that had radiography, ultrasonography, and antegrade pyelography
      performed for suspected ureteral obstructions were examined. Ultrasound-guided
      pyelocentesis and fluoroscopic-assisted antegrade pyelography were performed on
      18 kidneys in 11 cats. Obstructive ureteral lesions were confirmed in all cats by
      surgical or necropsy examination. Sensitivity and specificity of survey
      radiography, ultrasonography, and antegrade pyelography for identification of
      ureteral obstructions were calculated. Surgical or necropsy findings were used as
      the standard for comparison. RESULTS: All cats were azotemic. Mean +/- SD serum
      creatinine and BUN concentrations were 10.2 +/- 6.1 and 149 +/- 82 mg/dL,
      respectively. Fifteen of 18 ureters were found to be obstructed at surgery or
      necropsy. Sensitivity and specificity were 60 and 100% for radiography and 100
      and 33% for ultrasonography, respectively, in identification of ureteral
      obstructions. Leakage of contrast material developed in 8 of 18 kidneys during
      antegrade pyelography and prevented diagnostic interpretation in 5 of 18 studies.
      For the 13 diagnostic studies, specificity and sensitivity were 100% by use of
      the antegrade pyelography technique. Correct identification of the anatomic
      location of the ureteral obstruction was obtained in 100% of diagnostic antegrade
      pyelography studies and in 60% of radiography or ultrasonography studies.
      CONCLUSIONS AND CLINICAL RELEVANCE: Antegrade pyelography can be a useful
      alternative in the diagnosis and localization of ureteral obstructions in
      azotemic cats, although leakage of contrast material may prevent interpretation
      of the study.

PMID- 12784967
TI  - Antimicrobial resistance of bacteria isolated from dairy cow milk samples
      submitted for bacterial culture: 8,905 samples (1994-2001).
AB  - OBJECTIVE: To determine whether antimicrobial resistance patterns of major
      mastitis pathogens isolated from milk samples from dairy cows have changed over
      time. DESIGN: Retrospective study. SAMPLE POPULATION: 8905 bacterial isolates
      obtained from milk samples submitted to the Wisconsin Veterinary Diagnostic
      Laboratory between January 1994 and June 2001. PROCEDURE: Antimicrobial
      susceptibility was determined by means of the Kirby-Bauer disk diffusion method.
      Logistic regression was used to determine whether percentages of isolates
      resistant to various antimicrobials changed over time. RESULTS: For the gram
      positive mastitis pathogens, percentages of isolates resistant to various flactam
      antimicrobials did not increase over the course of the study. Percentage of
      Staphylococcus aureus isolates resistant to penicillin decreased from 49 to 30%;
      percentage of Streptococcus isolates resistant to penicillin decreased from 6 to
      1%. Percentage of isolates resistant to erythromycin increased for S aureus,
      Escherichia coli, Enterobacter spp, Enterococcus spp, and Pasteurella spp.
      Percentage of isolates resistant to lincomycin increased for S aureus and
      Staphylococcus spp. Percentage of coagulase-negative Staphylococcus isolates
      resistant to pirlimycin increased from 6 to 19%. For several pathogens,
      percentages of isolates resistant to sulfisoxazole and to trimethoprim
      sulfamethoxazole decreased. No pathogens had a significant increase in the
      percentage of isolates resistant to novobiocin-penicillin. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results did not indicate a trend toward increased
      antimicrobial resistance among mastitis pathogens isolated from milk samples from
      dairy cows between 1994 and 2001. Reduced resistance to flactam antimicrobials
      was identified for several gram-positive mastitis pathogens.

PMID- 12784968
TI  - GOLDmineR: improving models for classifying patients with chest pain.
AB  - The laboratory is dealing with reporting tests as information needed to make
      clinical decisions. The traditional statistical quality control measures which
      assigns reference ranges based on 95 percent confidence intervals is insufficient
      for diagnostic tests that assign risk. We construct a basis for risk assignment
      by a method that builds on the 2 x 2 contingency table used to calculate the C2
      goodness-of-fit and Bayesian estimates. The widely used logistic regression is a
      subset of the regression method, as it only considers dichotomous outcome
      choices. We use examples of multivalued predictor(s) and a multivalued as well as
      dichotomous outcome. Outcomes analyses are quite easy using the ordinal logit
      regression model.

PMID- 12784969
TI  - The impact of burnout on human physiology and on operational performance: a
      prospective study of soldiers enrolled in the combat diver qualification course.

PMID- 12784971
TI  - Aortic dissection presenting as acute lower extremity ischemia: report of a case.
AB  - Although not common, acute leg ischemia is an important element in the clinical
      presentation of a patient with aortic dissection. This report describes a case of
      aortic dissection in which the main feature at presentation was acute right leg
      ischemia. The angiography showed right common iliac artery and external iliac
      artery occlusion. Diagnosis was made by clinical evaluation and angiography.
      Embolectomy was then attempted immediately but failed. Aortic dissection was
      highly suspected and confirmed by emergency computed tomography. Fortunately, the
      patient had good recovery. Aortic dissection is potentially lethal if
      misdiagnosed or if recognition is delayed. As such, aortic dissection should be
      considered in the differential diagnosis.

PMID- 12784970
TI  - Vulvar syringoma, report of a case and review of the literature.
AB  - Syringomas are common intraepidermal sweat gland tumors most often found in women
      around the time of adolescence. Frequent sites of involvement include the lower
      eyelids and malar areas, however vulvar involvement is relatively rare. These
      lesions often present as small, multiple, skin-colored-to-yellowish papules and
      are often associated with increased vulvar discomfort and itching. We present a
      case of a 29-year old female who presented to her gynecologist complaining of
      vulvar itching and burning. A small condylomatous-type wart observed on her vulva
      was biopsied and found to be a syringoma. Because of their clinical presentation
      and associated symptoms, vulvar syringomas should be considered in the
      differential diagnosis of any multicentric papular lesion of the vulva, vulvar
      pain syndrome, and pruritus vulvae.

PMID- 12784973
TI  - The incidence of alkaptonuria: a study in chemical individuality. 1902 [classical
      article].

PMID- 12784974
TI  - Harold Varmus.

PMID- 12784972
TI  - Ribozyme therapy: RNA enzymes to the rescue.

PMID- 12784975
TI  - Acoustic neuroma in patients with completely resolved sudden hearing loss.
AB  - Approximately 30% of patients with sudden hearing loss show complete recovery.
      Researchers have long questioned whether extensive evaluation is necessary in
      these cases. Recently, however, with the increasing widespread application of
      magnetic resonance imaging, a higher rate than expected of acoustic neuromas has
      been detected in patients with sudden hearing loss. Two studies have suggested
      that affected patients may even partially regain hearing. The aim of the present
      clinical study was to determine whether acoustic neuroma-induced hearing loss may
      be associated with full recovery. The files of 67 patients evaluated for sudden
      hearing loss at Rabin Medical Center from 1989 to 2000 were reviewed. All
      patients underwent pure tone audiometry, acoustic reflex tests, and auditory
      brain stem evoked response tests. Hearing evaluation was followed by magnetic
      resonance imaging scan and, 1 month later, a second hearing test. Findings were
      compared between patients with and without evidence of tumor on imaging, and
      between patients with tumor with and without full recovery. Twenty-four patients
      (36%) had a diagnosis of acoustic tumor, of whom 4 (16.7%) recovered hearing
      after 1 month. All 4 tumors were intracanalicular. Two of these patients had low
      tone hearing loss, and 2 had flat curves; 3 had a pathological auditory brain
      stem evoked response. Of the 43 patients without tumors, 26 (60%) showed complete
      resolution of the hearing loss. We conclude that complete recovery of hearing
      loss does not exclude acoustic tumor, and these patients therefore require full
      evaluation. The reason for the recovery remains unclear.

PMID- 12784976
TI  - Otosclerosis and chronic tinnitus.
AB  - Chronic subjective tinnitus is a common feature of clinical otosclerosis.
      Analysis of the records of 1,014 consecutive cases of clinical otosclerosis, all
      confirmed by stapes surgery in South Australia between 1960 and 1972, gives a
      preoperative prevalence of this symptom of 65%. The association of tinnitus with
      various predictors is considered, and a statistical analysis is presented.
      Tinnitus has an association with gender (p < .0001), mean preoperative bone
      conduction (BC) level (p = .0012), mean air conduction (AC) level (p = .0192),
      and mean air-bone gap (p = .0075). The associations between tinnitus and the age
      of the patient, the duration of deafness, the presence of Schwartze's sign, and
      the severity of footplate pathological involvement were all nonsignificant. The
      association of tinnitus with the AC and BC thresholds is unexpectedly
      paradoxical. An economic predictive model for tinnitus in otosclerosis has been
      constructed from the 2 strongly significant variables, gender and mean BC hearing
      level, by logistic regression. In this large series of cases, the log odds in
      favor of finding tinnitus are about 0.810 for male subjects and 1.394 for female
      subjects when the BC level is zero. The log odds fall by 0.014 for each decibel
      of mean BC rise.

PMID- 12784977
TI  - Reduction of postural sway by use of a vibrotactile balance prosthesis prototype
      in subjects with vestibular deficits.
AB  - To evaluate the effectiveness of a prototype vibrotactile balance prosthesis in
      maintaining balance during dynamic posturography, we studied 6 subjects with
      unilateral or bilateral vestibular deficit by means of Equitest computerized
      dynamic posturography (CDP). Their anterior-posterior (AP) sway at the small of
      the back was measured with a micromechanical rate gyroscope and a linear
      accelerometer. The resulting tilt estimate was displayed by a vibrotactile array
      attached to the torso. The vibration served as tilt feedback to the subject.
      Subject performance was evaluated with the tilt performance index (TPI), which is
      the inverse of the root-mean-square of tilt. We found that the balance prosthesis
      reduced the subjects' AP sway. The subjects' results without the balance
      prosthesis on CDP sensory organization tests (SOTs) 5 and 6 were compared to
      results with the prosthesis. The average TPI increased significantly (p < .05)
      when vibrotactile feedback was used as compared to the unaided condition. This
      finding was true for both SOTs 5 and 6. We conclude that vibrotactile feedback of
      estimated AP body tilt improved the subjects' ability to perform selected CDP
      tests. Some of the subjects were able to stand throughout the test with the
      device turned on, whereas they otherwise constantly fell.

PMID- 12784978
TI  - Effect of modern fibrin glue on bleeding after tonsillectomy and adenoidectomy.
AB  - We performed a prospective randomized study in 179 patients to examine the second
      generation surgical fibrin sealant Quixil as an effective substitute for
      different types of electrocautery in tonsillectomy and adenoidectomy. We compared
      the rates of hemorrhagic complications in a group with bipolar or needle point
      electrocautery and in a group in whom fibrin glue was used to stop intraoperative
      bleeding and to prevent postoperative bleeding. The operations were performed
      under general anesthesia in typical fashion with sharp dissection. For the
      control group, hemostasis was achieved by bipolar or needle point electrocautery.
      For the fibrin glue group, hemostasis was achieved by spraying Quixil fibrin glue
      approximately 0.5 mL to each tonsillar fossa and 0.5 mL to the nasopharynx (in
      adenoidectomy). The results were excellent in all the patients of the fibrin glue
      group, with complete hemostasis and resolution of the major symptoms. In this
      group, the intraoperative blood loss averaged 15 mL in tonsillectomy and 9 mL in
      adenoidectomy. There were no cases of postoperative hemorrhage or any other
      complications. The electrocautery group required a longer time for healing, and
      its intraoperative blood loss (tonsillectomy) averaged 29 to 33 mL. The incidence
      of posttonsillectomy bleeding in this group was 4.35% (4 patients). Three
      patients (3.26%) had primary hemorrhage (bleeding that occurs within the first 24
      hours of surgery), and 1 patient (1.09%) had secondary hemorrhage (bleeding that
      occurs after the first 24 hours). We conclude that Quixil fibrin glue application
      to the operative sites in tonsillectomy and adenoidectomy provides effective
      hemostasis and sealing with good systemic and local compatibility. With the help
      of Quixil, we minimized surgical trauma and achievedabsolute hemostasis at the
      same time. We found this fibrin glue to be a more convenient and effective
      hemostatic sealant than bipolar or needle point coagulation.

PMID- 12784979
TI  - Detection of recurrent nasopharyngeal carcinomas with technetium-99m
      methoxyisobutylisonitrile single photon emission computed tomography in patients
      with indeterminate magnetic resonance imaging findings after radiotherapy.
AB  - The aim of this study was to evaluate the effectiveness of technetium-99m
      methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed
      tomography (SPECT) for detecting recurrent nasopharyngeal carcinomas (NPCs) when
      magnetic resonance imaging (MRI) findings are indeterminate. Twenty-eight NPC
      patients who had received radiotherapy and had indeterminate MRI findings were
      included in the study. We performed MRI, Tc-99m MIBI SPECT, and biopsy at least 4
      months after radiotherapy and within 1 week. The final results were based on
      histopathologic findings and clinical follow-up after 6 or more months. For
      detecting recurrent NPC in indeterminate MRI findings, the sensitivity,
      specificity, and accuracy of Tc-99m MIBI SPECT were 85.7%, 92.9%, and 89.3%,
      respectively. Our findings suggest that Tc-99m MIBI SPECT may be an effective
      tool for detecting recurrent NPC when MRI findings are indeterminate.

PMID- 12784980
TI  - Three-dimensional analysis of morphological aspects of the human utricular
      macula.
AB  - The 3-dimensional shape of the human utricular macula and its orientation in the
      skull are quantitated in this report, which is one of a series. The semicircular
      canals and utricular macula were reconstructed in 3 dimensions on a computer from
      3 human temporal bones. The 238 to 279 triangles in the entire area of the
      utricular macula were made by drawing lines between 2 adjacent points every 200
      microm width of the utricular macula in each section. We calculated the angles
      between each triangle and each estimated standard axis in the skull. This study
      provides standard data regarding the 3-dimensional morphological aspects of the
      utricular macula for further investigation of the function of the utriculus. We
      determined that the 3-dimensional shape of the utricular macula was not a plane,
      but was a curved surface like that of an ellipsoid. We believe this shape is
      necessary for the utricular macula to detect wide-range linear acceleration.

PMID- 12784981
TI  - Scuba diving with cochlear implants.
AB  - We report on a patient with bilateral cochlear implants (a Med-El Combi40 and a
      Med-El Combi40+), as well as considerable experience in scuba diving with both of
      his implants. After having been exposed to 68 and 89 dives, respectively, in
      depths of up to 43 m, both cochlear implants are in working order and the patient
      continues to receive excellent speech recognition scores with both cochlear
      implant systems. The presented data show that scuba diving after cochlear
      implantation is possible over a considerable number of dives without any major
      negative impact on the implants.

PMID- 12784983
TI  - Surgical anatomy of the recurrent laryngeal nerve: implications for laryngeal
      reinnervation.
AB  - Functional laryngeal reinnervation depends upon the precise reinnervation of the
      laryngeal abductor and adductor muscle groups. While simple end-to-end
      anastomosis of the recurrent laryngeal nerve (RLN) main trunk results in
      synkinesis, functional reinnervation can be achieved by selective anastomosis of
      the abductor and adductor RLN divisions. Few previous studies have examined the
      intralaryngeal anatomy of the RLN to ascertain the characteristics that may lend
      themselves to laryngeal reinnervation. Ten human larynges without known laryngeal
      disorders were obtained from human cadavers for RLN microdissection. The
      bilateral intralaryngeal RLN branching patterns were determined, and the
      diameters and lengths of the abductor and adductor divisions were measured. The
      mean diameters of the abductor and adductor divisions were 0.8 and 0.7 mm, while
      their mean lengths were 5.7 and 6.1 mm, respectively. The abductor division
      usually consisted of one branch to the posterior cricoarytenoid muscle; however,
      in cases in which multiple branches were seen, at least one dominant branch could
      usually be identified. We conclude that the abductor and adductor divisions of
      the human RLN can be readily identified by an extralaryngeal approach. Several
      key landmarks aid in the identification of the branches to individual muscles.
      These data also indicate the feasibility of selective laryngeal reinnervation in
      patients who might be candidates for laryngeal transplantation after total
      laryngectomy.

PMID- 12784982
TI  - Extracellular matrix as a scaffold for laryngeal reconstruction.
AB  - Porcine-derived xenogeneic extracellular matrix (ECM) has been successfully used
      as a scaffold for tissue repair and reconstruction in numerous preclinical animal
      studies and human applications. These scaffolds are completely and rapidly
      degraded and replaced by host-derived tissues that frequently mimic the original
      tissue composition and architecture. The purpose of the present study was to
      examine the morphology of ECM scaffolds after their use for laryngeal
      reconstruction. Thirty adult female dogs were subjected to a partial
      hemilaryngectomy. The right thyroid cartilage and vocal fold were replaced with
      ECM scaffold, and the dogs were painlessly sacrificed from 1 week to 12 months
      after surgery. Histologic examination of the reconstructed tissue showed the
      presence of a simple squamous epithelial lining, organized glandular structures
      within the submucosa, reconstructed thyroid cartilage, and bundles of skeletal
      muscle by 3 months after surgery. We conclude that ECM scaffolds are promising
      templates for constructive remodeling of laryngeal tissue.

PMID- 12784984
TI  - Difference in attachment of the tensor veli palatini muscle to the eustachian
      tube cartilage with age.
AB  - To test a hypothesis that ventilation of the eustachian tube (ET) varies with
      age, we investigated the relationship between age and the attachment of the
      tensor veli palatini muscle (TVPM) to the lateral lamina of the ET cartilage in
      12 normal human temporal bones obtained from individuals 3 months to 81 years
      old. We used computer-aided 3-dimensional reconstruction and measurement methods.
      We found that the length of the TVPM attachment and its ratio to the length of
      the ET, especially that of the cartilaginous portion of the ET, increases with
      age from infancy to adulthood, and decreases with age from young adulthood to
      later life. These findings are thought to be related to postnatal development and
      aging. The possibility of differences in ventilation function with age is
      discussed.

PMID- 12784985
TI  - Hammer-chisel technique in endoscopic dacryocystorhinostomy.
AB  - We performed a prospective evaluation of endoscopic hammer-chisel
      dacryocystorhinostomy (DCR) procedures on 62 eyes of 44 patients (40 female and 4
      male) with chronic epiphora or dacryocystitis (26 unilateral and 18 bilateral).
      The technique included chisel removal of bone over the lacrimal sac. The follow
      up period was 12 to 54 months (mean, 28 months), and the patients' ages ranged
      from 17 to 67 years (mean, 35.5 years). The success rate of the consecutive
      endoscopic hammer-chisel DCR procedures was 87%. During operation, 8 patients had
      mild mucosal hemorrhage, which did not prevent the successful completion of the
      operation. Excellent patient tolerance was observed, with minimal morbidity and
      no major complications. As compared to the external approach, endoscopic hammer
      chisel DCR is less traumatic, is less time-consuming, and is practical and
      cosmetically convenient, with minimal perioperative and postoperative
      complications. It also allows the simultaneous correction of any intranasal
      disease. It requires minimal instrumentation and is a relatively easy and fast
      technique.

PMID- 12784986
TI  - Characteristics of the type B tympanogram can predict the magnitude of the air
      bone gap in otitis media with effusion.
AB  - Tympanometry is well established as a means of assessing the presence of fluid in
      the middle ear. The type B tympanogram is usually considered a unique entity.
      However, its shape may vary from a rounded type B with a "pseudopeak" to a
      completely flat response. The aim of this study was to compare the
      characteristics of the B curve (maximum admittance, tympanometric peak pressure,
      and area under the curve) to the viscosity of the middle ear fluid and to the air
      bone gap (ABG). In 67 children (93 ears) who underwent ventilation tube
      insertion, no correlation was found between the viscosity of the middle ear fluid
      and the characteristics of the B curve. However, these characteristics were able
      to differentiate between a low ABG (0 to 20 dB) and a high ABG (>20 dB). A
      statistical difference was also found for the three parameters (maximum
      admittance, p < .0025; pressure, p < .025; and area under the curve, p < .0005).
      Tympanometry may be used as an objective measure to estimate the extent of
      conductive hearing loss, especially in young children.

PMID- 12784987
TI  - Laser surgery of the inferior turbinate for allergic rhinitis with seasonal
      exacerbation: an acoustic rhinometry study.
AB  - Laser surgery has been used to successfully treat patients with perennial
      allergic rhinitis. We examined whether the numbers and types of sensitized
      allergens influence the effects of surgery. Two different groups (those allergic
      to house dust mites only, and those allergic to house dust mites and Japanese
      cedar pollen) prospectively underwent the same course of laser turbinectomy
      during the pollen dispersion season. The symptom scores for nasal obstruction
      significantly decreased in both groups, but the improvement of sneezing and
      rhinorrhea was less pronounced in the pollen group. We used acoustic rhinometry
      to measure postoperative changes in the nasal dimensions. Four months after
      treatment, the minimum cross-sectional area and nasal cavity volume had
      increased, respectively, by 61.7% and 30.7% in the house dust group, and by 30.7%
      and 16.2% in the pollen group. We conclude that laser surgery can be successfully
      applied to patients whose allergies show seasonal exacerbation by airborne
      pollen.

PMID- 12784988
TI  - Effects of bacterial toxins on air-exposed cultured human respiratory sinus
      epithelium.
AB  - The present study was designed to investigate the effects of the bacterial toxins
      lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on air-exposed cultured
      human respiratory sinus epithelium. The morphological changes, proliferation, and
      differentiation of sphenoid sinus mucosa were examined after incubation with
      different LPS or LTA concentrations. Air-exposed cultured sinus mucosa
      differentiated from pseudostratified respiratory epithelium to squamous ciliated
      epithelium with few goblet cells. High concentrations of bacterial toxins induced
      a significant increase in mucus production and a decrease in ciliated cells. Ki67
      immunostaining showed an increased cell proliferation after incubation with
      moderate levels of LPS or LTA. High concentrations of bacterial toxins, on the
      other hand, induced a decreased proliferation. Involucrin expression was clearly
      altered by incubation with high levels of bacterial toxins, indicating an
      increased degree of terminal differentiation. These results indicate that the
      bacterial toxins LPS and LTA both induce comparable dose-dependent morphological
      changes in sinus epithelium.

PMID- 12784989
TI  - Predictive value of accumulated oropharyngeal secretions for aspiration during
      video nasal endoscopic evaluation of the swallow.
AB  - The purpose of this prospective study was to investigate the predictive value of
      oropharyngeal secretions by use of 5-point and modified 3-point secretion scales
      for aspiration of food or liquid and diet recommendation outcomes. One hundred
      consecutive patients and 4 control subjects participated. The 5-point secretion
      severity scale correlated highly to aspiration (Spearman's rho = .516, p < .0001)
      and to diet recommendation outcomes (Spearman's rho = .72, p < .0001). Patients
      who received tube feedings were more likely to demonstrate a higher secretion
      level than patients who received oral feedings (Pearson chi squared analysis
      value = 25.461, p < .0001). Patients with a tracheotomy tube tended to
      demonstrate higher secretion levels than patients without a tracheotomy tube
      (Spearman's rho = .446, p < .0001). The relationship of the 3-point secretion
      severity scale level with aspiration was .488, p < .0001 (Spearman's rho), and
      that with diet recommendation outcomes was .746, p < .0001 (Spearman's rho).

PMID- 12784990
TI  - Hypertrophic cranial pachymeningitis presenting as steroid-responsive hearing
      loss.

PMID- 12784991
TI  - Effect of acoustic tumor extension into the internal auditory canal on distortion
      product otoacoustic emissions.

PMID- 12784992
TI  - Role of pericellular proteolysis by membrane-type 1 matrix metalloproteinase in
      cancer invasion and angiogenesis.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane
      proteinase that is frequently expressed in malignant cancer cells and has potent
      invasion-promoting activity. When expressed on the cell surface, MT1-MMP degrades
      the extracellular matrix (ECM) barrier adjacent to the cells to maintain the
      migration route to traverse the tissue. But MT1-MMP is not just an enzyme that
      degrades ECM. MT1-MMP also introduces limited cleavage into proteins at the cell
      ECM interspaces and converts their functions. The target molecules are ECM
      components, cell adhesion molecules, and latent forms of MMPs. Through these
      processing events MT1-MMP modulates the migratory and invasive behavior of the
      cells.

PMID- 12784993
TI  - MT1-MMP and MMP-7 in invasion and metastasis of human cancers.
AB  - Previous experimental and biochemical studies on matrix metalloproteinases (MMPs)
      have indicated that MMPs are implicated in cancer invasion and metastases.
      Studies on the expression of MMPs and tissue inhibitors of metalloproteinases
      (TIMPs) in various human cancer tissues have further demonstrated that activation
      of proMMP-2 mediated by a combination of TIMP-2 and MT1-MMP (the proMMP-2/TIMP
      2/MT1-MMP system) correlates well with the progression of most of these cancers
      such as the breast carcinomas, thyroid papillary carcinomas, gastric
      adenocarcinomas, oral squamous cell carcinomas and gliomas, whereas MMP-7 plays
      an important role in the metastases of endometrial and gastrointestinal
      carcinomas. Although MMP-7 is a typical secreted MMP, a member of transmembrane 4
      superfamily (TM4SF) captures proMMP-7 on the carcinoma cell membranes through
      interaction with its propeptide, leading to its pericellular activation. Thus,
      these results strongly suggest that proteolysis at the cell-extracellular matrix
      interfaces of cancer cells by the proMMP-2/TIMP-2/MT1-MMP and proMMP-7/TM4SF
      systems plays crucial roles in the progression of human cancers. In this article,
      we address the current views on the roles of these MMPs acting onthe cell
      membranes in human cancer invasion and metastases.

PMID- 12784994
TI  - Cell surface association of matrix metalloproteinase-9 (gelatinase B).
AB  - Matrix metalloproteinase (MMP)-9 (gelatinase B) belongs to the MMP family of zinc
      dependent endopeptidases that has been associated with tumor cell invasion and
      metastasis and tumor-induced angiogenesis. As a secreted MMP, pro-MMP-9 is
      released into the extracellular environment by both tumor and stroma cells, where
      it fulfills its proteolytic functions degrading both extracellular matrix (ECM)
      and non-ECM proteins. A major dilemma in our understanding of MMP-9 function is
      how the released protease is targeted to the right location and how its activity
      is controlled at the pericellular space. It has been proposed that MMP-9 interact
      with cell surface components and that this type of interaction positively
      regulates enzymatic activation and activity. However, recent evidence shows that
      association of MMP-9 with the cell surface is mediated by a distinct array of
      surface proteins that serve to regulate multiple aspects of the enzyme function
      including localization, inhibition and internalization. How these distinct
      mechanisms regulate the overall MMP-9 activity at the pericellular space remains
      an important goal in our understanding of MMP-9 function at the cell surface.
      Furthermore, the study of surface-associated MMP-9 imposes new conceptual and
      methodological challenges with particular consideration to the unique structural
      and functional characteristics of this key enzyme.

PMID- 12784995
TI  - RECK: a novel suppressor of malignancy linking oncogenic signaling to
      extracellular matrix remodeling.
AB  - RECK was first isolated as a transformation suppressor gene by cDNA expression
      cloning in a mouse fibroblast cell line transformed by an activated RAS oncogene.
      Subsequently, reduced expression of RECK in transformed cells and cancer cells
      were demonstrated. Moreover, in several types of tumors, positive correlation
      between RECK expression and survival of patients have been noted. RECK encodes a
      GPI-anchored glycoprotein harboring three protease inhibitor-like domains. The
      RECK protein regulates at least three members of the matrix metalloproteinase
      (MMP) family, MMP-2, MMP-9, and MT1-MMP, in vitro or in cultured cells. Restored
      expression of RECK in cancer cell lines results in strong suppression of
      invasion, metastasis, and tumor angiogenesis. Mice lacking RECK die in utero with
      reduced integrity of blood vessels, the neural tube, and mesenchymal tissues. In
      these mice, MMP activity is elevated, and the amount of collagen type I greatly
      reduced. The RECK null phenotype is partially rescued (half day delay of death
      and marked recovery of tissue integrity) by MMP-2 null mutation, demonstrating
      functional interaction between RECK and MMP-2 in vivo and involvement of other
      target(s) for RECK in the lethal phenotype. These findings indicate that (i) RECK
      is an important regulator of extracellular matrix remodeling and that (ii) down
      regulation of RECK by oncogenic signaling leads to the excessive activation of
      MMPs thereby promoting malignant behavior of cancer cells such as invasion,
      metastasis, and angiogenesis.

PMID- 12784996
TI  - Matrix metalloproteinase inhibitors (MMPIs): the beginning of phase I or the
      termination of phase III clinical trials.
AB  - The decade of the 1990s was ripe with enthusiasm for the use of MMPIs to treat
      cancer. Limitations to new cytotoxic chemotherapy approaches to treat solid
      cancers and a better understanding of tumor biology provided a strong impetus for
      alternative drug development. It is estimated that the pharmaceutical industry
      invested at least a billion dollars in this effort. Because MMPIs represent an
      entirely different therapeutic modality from proven anti-cancer agents, many of
      the therapeutic trials designed to test MMPIs in human patients with cancer
      bypassed traditional approaches to evaluate drug efficiency. The concept of
      systematic progression from small phase I (dose escalation to toxicity to examine
      drug safety), to phase II (drug treatment of patients with cancer types
      considered to be good candidates for the selected drug), to phase III (randomized
      trial of new drug versus best available therapy to determine drug efficacy)
      trials was modified. Much to the chagrin of everyone involved in these studies,
      the randomized trials of MMPIs in advanced cancer have, pretty much, flopped.
      This review article will attempt to dissect out aspects of previous human and
      animal studies that may be helpful in making decisions about the future of MMPI
      drug development for the treatment of cancer. The important questions to be
      addressed in this report are: What are the lessons that we have learned from
      preclinical (animal models) and clinical studies of MMPIs in cancer? Are we ready
      to abandon MMPIs as a therapeutic modality in cancer (termination of phase III
      trials) or do we need to have a better understanding of the myriad effects of
      MMPs in cancer before we proceed to develop different types of drugs that alter
      MMP activity in patients with cancer (beginning of new phase I trials)?

PMID- 12784997
TI  - The urokinase plasminogen activator system in cancer: recent advances and
      implication for prognosis and therapy.
AB  - Cancer dissemination and metastasis is synonymous with invasive cell migration; a
      process in which the extracellular matrix (ECM) plays the dual role of the
      substratum on which the cells move as well as the physical obstacle that the
      cells have to surpass. To degrade the physical obstacle, which the ECM poses in
      the direction of migration, cells use proteolytic enzymes capable of degrading
      the ECM components. A major protease system responsible for ECM degradation is
      the plasminogen activation system, which generates the potent serine protease
      plasmin. The subject of this review, the urokinase-type plasminogen activator
      (uPA) and its receptor (uPAR), plays an impressive range of distinct, but
      overlapping functions in the process of cancer invasion and metastasis: Firstly,
      uPA/uPAR promotes extracellular proteolysis by regulating plasminogen activation.
      Secondly, uPA/uPAR regulates cell/ECM interactions as an adhesion receptor for
      vitronectin (Vn) and through its capacity to modulate integrin function. Thirdly,
      uPA/uPAR regulates cell migration as a signal transduction molecule and by its
      intrinsic chemotactic activity. This review is focused on recent insight into the
      cancer related biology of the uPA/uPAR system as well as its implications for
      clinical cancer diagnosis, prognosis and therapy.

PMID- 12784998
TI  - Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in
      the pericellular activation of HGF/scatter factor.
AB  - The activation of hepatocyte growth factor (HGF)/scatter factor (SF) in an
      extracellular milieu is a critical limiting step in HGF/SF-induced signaling that
      is believed to have important roles in invasive growth of tumor cells and
      regeneration of injured tissue. This activation is caused by a proteolytic
      cleavage at the bond between Arg494-Val495 in the single-chain HGF/SF precursor,
      generating an active two-chain heterodimeric form. The HGF activator (HGFA) is a
      coagulation factor XII-like serine proteinase critically involved in this process
      in injured tissues including tumor tissues. In the past several years, the
      identification of endogenous HGFA inhibitors (HAIs) has provided detailed
      knowledge of the regulation of HGFA activity. Currently, two types of HAIs,
      namely HAI-1 and HAI-2, have been reported. Both are Kunitz-type serine
      proteinase inhibitors and inhibit not only HGFA but also other serine
      proteinases, such as membrane-type serine protease 1 (matriptase), plasmin,
      trypsin and kallikreins. HAIs are of particular interest because they are
      synthesized as type-I transmembrane proteins. Therefore, HAIs must have important
      regulatory roles in a cell surface proteolytic reaction, which has emerged as an
      important mechanism for the generation of biologically active proteins mediating
      a diverse range of cellular functions. This review is a summary and
      interpretation of recent data regarding the regulation of pericellular HGF/SF
      activation mediated by HGFA and HAIs and includes a discussion of the possible
      role of the type I transmembrane Kunitz-type inhibitor in pericellular
      proteolysis.

PMID- 12784999
TI  - Membrane anchored serine proteases: a rapidly expanding group of cell surface
      proteolytic enzymes with potential roles in cancer.
AB  - Dysregulated proteolysis is a hallmark of cancer. Malignant cells require a range
      of proteolytic activities to enable growth, survival, and expansion. Serine
      proteases of the S1 or trypsin-like family have well recognized roles in the
      maintenance of normal homeostasis as well as in the pathology of diseases such as
      cancer. Recently a rapidly expanding subgroup of S1 proteases has been recognized
      that are directly anchored to plasma membranes. These membrane anchored serine
      proteases are anchored either via a carboxy-terminal transmembrane domain (Type
      I), a carboxy terminal hydrophobic region that functions as a signal for membrane
      attachment via a glycosyl-phosphatidylinositol linkage (GPI-anchored), or via an
      amino terminal proximal transmembrane domain (Type II or TTSP). The TTSPs also
      encode multiple domains in their stem regions that may function in regulatory
      interactions. The serine protease catalytic domains of these enzymes show high
      homology but also possess features indicating unique substrate specificities. It
      is likely that the membrane anchored serine proteases have evolved to perform
      complex functions in the regulation of cellular signaling events at the plasma
      membrane and within the extracellular matrix. Disruption or mutation of several
      of the genes encoding these proteases are associated with disease. Many of the
      membrane anchored serine proteases show restricted tissue distribution in normal
      cells, but their expression is widely dysregulated during tumor growth and
      progression. Diagnostic or therapeutic targeting of the membrane anchored serine
      proteases has potential as promising new approaches for the treatment of cancer
      and other diseases.

PMID- 12785000
TI  - Seprase complexes in cellular invasiveness.
AB  - A group of type II integral serine proteases, including dipeptidyl peptidase IV
      (DPP4/CD26), seprase/fibroblast activation protein alpha (FAPalpha) and related
      type II transmembrane prolyl serine peptidases, exert their mechanisms of action
      on the cell surface. DPP4 and seprase exhibit multiple functions due to their
      abilities to form complexes with each other and to interact with other membrane
      associated molecules. Localization of the protease complexes at cell surface
      protrusions, called invadopodia, may have a prominent role in processing soluble
      factors (including chemokines and neuropeptide Y) and in degrading locally
      extracellular matrix components, that are essential to the cell migration and
      matrix invasion occurring during tumor invasion, angiogenesis and metastasis.

PMID- 12785001
TI  - Pericellular cathepsin B and malignant progression.
AB  - Cathepsin B is a lysosomal cysteine protease in normal cells and tissues. In
      malignant tumors and premalignant lesions, the expression of cathepsin B is
      highly upregulated and the enzyme is secreted and becomes associated with the
      cell surface. Increases in expression are mediated at many levels ranging from
      gene amplification to increased stability of mRNA and protein. Cathepsin B is
      synthesized as a preproenzyme and the primary pathways for its normal trafficking
      to the lysosome utilize mannose 6-phosphate receptors (MPRs). Inactive
      procathepsin B is processed to active single and double chain forms of cathepsin
      B in the late endosomes and lysosomes, respectively. Tumor cells secrete
      procathepsin B and both active forms of cathepsin B. Secretion of procathepsin B
      occurs principally as a result of increased expression, whereas secretion of
      active cathepsin B seems to involve active processes that can be induced by a
      variety of mechanisms. Once secreted procathepsin B binds to the tumor cell
      surface via p11, the light chain of the annexin II heterotetramer. This binding
      seems to facilitate conversion of procathepsin B to its active forms. Cathepsin B
      and the annexin II heterotetramer colocalize in caveolae (lipid raft) fractions
      isolated from tumor cells. Serine proteases and matrix metalloproteinases also
      have been found to associate with caveolae and some with the annexin II
      heterotetramer. Our working hypothesis is that pericellular cathepsin B through
      its proximity to other proteases in caveolae participates in, perhaps even
      initiates, a proteolytic cascade on the tumor cell surface.

PMID- 12785002
TI  - Patients with postoperative infections have sticky neutrophils before operation.
AB  - Appropriate polymorphonuclear neutrophil (PMN) recruitment is essential for host
      defense against infection. We investigated the significance of the preoperative
      PMN adhesion-migration process, as assessed by the flow chamber method, on
      postoperative infectious complications. Thirty-one consecutive patients with
      gastrointestinal malignancies, 21 colorectal and 10 gastric, who were undergoing
      elective surgery were enrolled. PMNs, isolated preoperatively from each patient's
      venous blood, were perfused onto a tumor necrosis factor alpha-stimulated human
      umbilical vein endothelial cell (HUVEC) monolayer through the flow chamber. We
      evaluated the adherent PMN number, the migrated PMN number, and the stuck PMN
      number by directly inspecting PMN interactions with a HUVEC monolayer under
      continuous shear flow simulating postcapillary venules. The expression of
      adhesion molecules on circulating PMNs was also measured. Patients were grouped
      into an infectious and a noninfectious group according to the occurrence of
      postoperative infectious complications defined by the Centers for Disease Control
      criteria. Eleven patients developed postoperative infectious complications.
      Although the number of preoperative in vitro adherent PMNs in patients with
      postoperative infection was significantly higher than in those without
      postoperative infection (P = 0.01), migrated PMN number was similar in both
      groups. Stuck PMN number tended to be higher in the infectious group than in the
      noninfectious group. The migrated PMN number showed a significant positive
      correlation with the adherent PMN number in the noninfectious group but not in
      the infectious group. Preoperative CD31 expression on circulating PMNs was
      significantly lower in the infectious group than in the noninfectious group.
      Preoperative in vitro derangement of the PMN adhesion-migration process is
      closely associated with postoperative infectious complications.

PMID- 12785003
TI  - Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin
      challenge in healthy volunteers.
AB  - Anti-inflammatory effects of adenosine were evaluated in two randomized, double
      blind, placebo-controlled studies. In one study healthy male volunteers received
      no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4
      ng/kg, endotoxin study n = 11) was given. All subjects were treated with
      adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a
      crossover design. Heart rate, body temperature, blood pressure and plasma
      cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-10, and
      soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and
      nitrate, as well as superoxide anions were determined. There were no significant
      changes of any measured parameter after adenosine treatment alone. Endotoxin
      elicited clinical signs of an inflammatory reaction, prominent release of all
      cytokines and O2- synthesis by neutrophils (N-formyl-methionin-leucyl
      phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL
      6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9
      (0.8-1.6) to 1345 (743-1906) pg/mL (median; 25-75th percentiles) with adenosine
      infusion, and from 0.8 (0.5-1) to 1,959 (1,344-2,505) pg/mL with placebo (P =
      0.0065). There was no significant influence of adenosine infusion on the other
      variables examined. In conclusion, systemic adenosine infusion counteracts the
      release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of
      adenosine which should be further explored.

PMID- 12785004
TI  - Fatty acids and glucose increase neutral endopeptidase activity in human
      microvascular endothelial cells.
AB  - Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that
      degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and
      endothelin may regulate response to injury. We have previously demonstrated
      increased NEP localization and enzyme activity in diabetic wounds and skin
      compared with normal controls. We hypothesized that hyperlipidemia and
      hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP
      activity and thereby diminish normal response to injury. Human microvascular
      endothelial cells were treated with five different fatty acids (40 microM) with
      varying degrees of saturation, including oleic acid, linoleic acid, palmitic
      acid, stearic acid, and linolenic acid and/or glucose (40 mM) for 48 h. The
      effect of the antioxidative agents vitamin E and C on NEP enzyme activation was
      determined by treating the cultured cells with alpha-tocopherol succinate and/or
      L-ascorbic acid. Cell membrane preparations were assayed for NEP activity by
      incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a
      fluorescent degradation product methoxy 2 naphthylamine. High glucose or fatty
      acid concentration upregulated NEP activity. The highest NEP activity was
      observed with combined elevated glucose, linoleic acid, and oleic acid (P <
      0.05). Antioxidant vitamin E and C treatment significantly reduced NEP enzyme
      activity after fatty acid exposure (P < 0.05). Thus, hyperglycemia and
      hyperlipidemia associated with type 2 diabetes mellitus may increase endothelial
      cell NEP activity and thereby decrease early pro-inflammatory responses. The
      modulator effect of vitamin E and C on NEP membrane enzyme activity after
      exposure to fatty acid stimulation suggests that lipid oxidation may activate
      NEP.

PMID- 12785005
TI  - Mast cells and resistance to peritoneal sepsis after burn injury.
AB  - A mouse model of burn injury demonstrates increasing mortality to an infectious
      challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10
      days after injury. Because it is widely believed that peritoneal mast cells play
      an important role in the defense against peritoneal sepsis, we wished to explore
      the possibility that peritoneal mast cell dysfunction contributed to increased
      CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack
      peritoneal mast cells by cytospin and flow cytometry, and normal littermate
      control animals were subjected to 25% burn or sham burn injury and 10 days later
      underwent CLP. Burn injured Kit(W-v) and normal littermates had a high CLP
      mortality when compared with sham-injured Kit(W-v) and normal littermates (P <
      0.003), but the sham- and burn-injured Kit(W-v) and normal littermate animals did
      not differ from one another with respect to CLP mortality. This result prompted a
      comparison of CLP mortality in untreated WBB6F1 Kit(W/W-v) mice, known to be mast
      cell deficient, and normal littermate controls, as well as untreated C57BL/6
      Kit(W-v) and normal littermates. The WBB6F1 Kit(W/W-v) mice showed significantly
      increased mortality after CLP as compared with the littermate controls (P =
      0.03), whereas both C57BL/6 Kit(W-v) and littermate controls had very low
      mortality after CLP. A study of peritoneal cell populations 24 h after CLP failed
      to reveal an obvious cause for the difference in CLP survival between the two
      mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements
      in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate
      controls of both strains and little in the fluid obtained from the mast cell
      deficient animals of both strains. We conclude that peritoneal mast cell
      dysfunction is unlikely to be a major cause of decreased resistance to peritoneal
      sepsis in burn-injured animals and that the importance of peritoneal mast cells
      in combating peritoneal sepsis in the mouse appears to be strain dependent.

PMID- 12785006
TI  - Cardiopulmonary, histological, and inflammatory alterations after lung contusion
      in a novel mouse model of blunt chest trauma.
AB  - Severe blunt chest trauma remains an important injury with high morbidity and
      mortality. However, the associated immunological alterations are poorly
      understood. Existing big animal models require large-scale settings, are often
      too expensive, and research products for immunological studies are limited. In
      this study we aimed to establish a new model of blunt, isolated and bilateral
      chest trauma in mice and to characterize its effects on physiological and
      inflammatory variables. Male C3H/HeN mice (n = 9-10/group) were anesthetized and
      a femoral artery was catheterized. The animals were subjected to trauma or sham
      procedure and monitored for 180 min. Blunt chest trauma was induced by a blast
      wave focused on the thorax. Trauma intensity was optimized by varying the
      exposure distance. Blood pressure, heart rate, respiratory rate, arterial blood
      gases and plasma cytokine levels were measured. Macroscopic and microscopic
      examinations were performed. In addition, outcome was evaluated in a 10-day
      survival study. Chest trauma caused a drop (P < 0.05) in blood pressure and heart
      rate, which partly recovered. Blood gases revealed hypoxemia and hypercarbia (P <
      0.05) 180 min after trauma. There was marked damage to the lungs but none to
      abdominal organs. Histologically, the characteristic signs of a bilateral lung
      contusion with alveolar and intrabronchial hemorrhage were found. Plasma
      interleukin-6 and tumor necrosis factor alpha were considerably increased after
      180 min. Blunt chest trauma resulted in an early mortality of 10% without
      subsequent death. On the basis of these findings, this novel mouse model of blunt
      chest trauma appears suitable for detailed studies on immunological effects of
      lung contusion.

PMID- 12785007
TI  - Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic
      porcine endotoxemia.
AB  - Heme oxygenase (HO) has both deleterious and protective effects in various shock
      models. Most of these data have been derived from experiments with hypodynamic
      shock states associated with depressed cardiac output. Therefore we studied the
      role of HO during long-term porcine hyperdynamic endotoxemia characterized by a
      sustained increase in cardiac output resulting from colloid resuscitation to
      maintain mean arterial pressure > 60 mmHg. Systemic, pulmonary, and
      hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin
      mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated
      animals. After 12 h of continuous intravenous lipopolysaccharide (LPS), animals
      received either vehicle (n = 6) or SnMP (n = 8; 6 micromol kg(-1) i.v. over 30
      min at 12 and 18 h of LPS). Measurements were performed before LPS, before SnMP
      infusion, and at 24 h of LPS. SnMP did not influence systemic hemodynamics but
      significantly increased mean pulmonary artery pressure. Although liver blood flow
      was not affected, SnMP markedly impaired liver lactate clearance. HO inhibition
      was associated with increased plasma nitrate levels likely the result of
      increased NO production. Our results suggest a protective role of HO activation
      during hyperdynamic porcine endotoxemia possibly as a result of an interaction
      with the LPS-induced increase in NO formation.

PMID- 12785008
TI  - G protein and adenylate cyclase complex-mediated signal transduction in the rat
      heart during sepsis.
AB  - Changes in the protein level of various subunits of GTP-binding protein and the
      activity of adenylate cyclase in the rat heart during different phases of sepsis
      were studied. Sepsis was induced by cecal ligation and puncture (CLP).
      Experiments were divided into three groups: control, early sepsis, and late
      sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h,
      respectively, after CLP. The protein levels of various subunits of GTP-binding
      protein were determined by Western blot analysis. The activity of adenylate
      cyclase was measured based on the rate of formation of cAMP from [alpha-32P]ATP.
      The results show that protein levels of G alphas and G beta remained stable
      during the early and the late phases of sepsis. The protein levels of G alpha i-2
      and G alpha i-3 remained relatively unaltered during the early phase of sepsis,
      but they were increased by 46.5% (P < 0.05) and 61.3% (P < 0.01), respectively,
      during the late phase of sepsis. The basal adenylate cyclase activity remained
      unchanged during the early phase while it was decreased by 25.7% (P < 0.05)
      during the late phase of sepsis. The isoproterenol-stimulated adenylate cyclase
      activity was unchanged during early sepsis while it was decreased by 44.6% (P <
      0.01) during late sepsis. These data demonstrate that during the late hypodynamic
      phase of sepsis, myocardial G alpha i-2 and G alpha i-3 protein levels were
      increased and the increases were coupled with a reduction in adenylate cyclase
      activity. Because GTP-binding proteins mediate sympathetic control of cardiac
      function, the present findings may have a pathophysiological significance in
      contributing to the understanding of the pathogenesis of cardiac dysfunction
      during the late stage of sepsis.

PMID- 12785009
TI  - Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis
      factor alpha, interleukin-1beta, -6, and high-mobility-group protein-1 in
      skeletal muscle.
AB  - The presence of increased levels of proinflammatory cytokines in the blood is
      associated with decreased muscle protein synthesis and the erosion of lean body
      mass in many catabolic conditions. However, little is known regarding the role of
      endogenous cytokine synthesis in muscle per se. The purpose of the present study
      was to characterize the cytokine expression profile of skeletal muscle in
      response to an in vivo injection of endotoxin (lipopolysaccharide, LPS).
      Intraperitoneal injection of a nonlethal dose of LPS (1,000 microg/kg Escherichia
      coli) into male rats increased the mRNA content of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin (IL)-1beta in gastrocnemius muscle as early as 1 h;
      IL-6 mRNA was not increased until 2 h post-LPS. Expression of TNF-alpha and IL
      1beta peaked at 2 h (10- and 80-fold, respectively), whereas the increased IL-6
      mRNA content (150-fold) peaked later at 4 h. The abundance of all measured
      cytokine mRNAs in skeletal muscle declined thereafter. The LPS-induced increase
      in muscle mRNA content for TNF-alpha, IL-6, and IL-1beta was dose-dependent with
      elevations being seen with as little as 10 microg/kg of LPS (2.5-, 8-, and 9
      fold, respectively). In general, pretreatment of rats with dexamethasone
      attenuated but did not completely prevent the LPS-induced increase in muscle
      cytokine mRNA. LPS increased muscle TNF-alpha protein content approximately 2
      fold and this increase was prevented by pretreatment with dexamethasone. LPS
      induced increases in muscle IL-1beta and IL-6 protein were not detected. LPS also
      produced a 2-fold increase in the mRNA content of the high-mobility-group protein
      1, a late-phase cytokine, in muscle at 12-24 h. Finally, although skeletal muscle
      was found to contain both the toll-like receptor (TLR)-2 and TLR4, LPS did not
      alter the mRNA content of TLR4 and produced a small (50%) but significant
      increase in TLR2 mRNA. These changes in TLRs were less dramatic than those
      observed for liver, spleen or cardiac muscle. Collectively these data indicate
      that skeletal muscle possesses many of the components of the innate immune
      system, including increases in both early- and late-phase cytokines and the
      presence of toll-like receptors.

PMID- 12785010
TI  - An AT1-receptor antagonist and an angiotensin-converting enzyme inhibitor protect
      against hypoxia-induced apoptosis in human aortic endothelial cells through
      upregulation of endothelial cell nitric oxide synthase activity.
AB  - The protective effects and roles of AT1-receptor antagonists (AT1-RA) or
      angiotensin-converting enzyme inhibitors (ACEI) on vascular endothelial cell (EC)
      injury during hypoxia are not entirely known. Therefore, we investigated these
      effects and mechanisms in human aortic (HA) EC. DNA fragmentation, Lactate
      dehydrogenase (LDH) release, and caspase-3 activity were measured in cultured
      HAEC after exposure to hypoxia in the presence or absence of an AT1-RA
      (candesartan, CS) and/or an ACEI (temocaprilat, TC). Next, we investigated
      endothelial cell nitric oxide synthase (ecNOS) and inducible (i) NOS to determine
      the role of the bradykinin(BK)-NO pathway in the protective effect on ACEI and
      AT1-RA in the setting of hypoxia-induced apoptosis. Exposure to hypoxia increased
      DNA fragmentation in HAEC associated with the activation of caspase-3, but did
      not affect LDH release. In addition, hypoxia induced ecNOS mRNA but not mRNA
      iNOS. CS and/or TC reduced apoptosis induced by hypoxia in a dose-dependent
      manner, and significantly increased BK and ecNOS expression. This effect was
      attenuated by the kinin B2 receptor antagonist, HOE 140, and the NOS inhibitor, N
      nitro-L-arginine methylester (L-NMMA). Hypoxia activates the pathway leading to
      apoptosis by enhancing caspase-3 activity. Both CS and TC can ameliorate hypoxia
      induced apoptosis in HAEC through inhibiting caspase-3 activation by enhancing
      ecNOS activity, via the accumulation of BK.

PMID- 12785011
TI  - Sustained tolerance to lipopolysaccharide after liver ischemia-reperfusion
      injury.
AB  - Liver ischemia-reperfusion injury (IR) would be expected to alter the capacity of
      previously ischemic as well as continuously perfused segments that are exposed to
      circulating inflammatory mediators to respond to a subsequent infectious insult.
      IR is reported to induce tolerance to subsequent endotoxin stimulation if the
      lipopolysaccharide (LPS) challenge is delayed until the late, neutrophil-mediated
      phase of reperfusion. Whether ischemic or perfused liver is differentially
      affected and whether LPS-tolerance may be overcome by increasing exposure is
      unknown. We hypothesized that late tolerance after IR reflects a refractory state
      in which the liver's expression of pro-inflammatory mediators in response to
      secondary LPS is limited. Precision-cut tissue culture methodology was used to
      investigate the capacity of rabbit liver to respond to a spectrum of LPS
      stimulation 24 h after partial IR. Slices from normal liver showed a dose
      dependent response to LPS for tumor necrosis factor (TNF-alpha) expression.
      Slices from both previously ischemic and continuously perfused lobes retained
      dose responsiveness for TNF-alpha, although TNF-alpha was significantly decreased
      at high LPS concentrations compared with normal liver. Ischemic liver sustained
      this blunted response despite extended exposure to LPS, whereas perfused slices
      recovered responsiveness to high dose LPS with prolonged stimulation. IR induced
      interleukin-8 in both ischemic and perfused liver, but secondary LPS stimulation
      did not augment interleukin-8 expression. Hepatic IR induces a late tolerance to
      secondary LPS challenge in locally ischemic tissue that cannot be overcome by
      increasing LPS exposure. Nonischemic liver exposed to the systemic effects of IR
      injury, however, retains a capacity to respond to LPS with sufficient
      stimulation.

PMID- 12785012
TI  - Ventilation-induced lung injury is associated with an increase in gut
      permeability.
AB  - Mechanical ventilation is associated with several harmful effects mainly related
      to high tidal volumes (Vt). Ventilator-induced lung injury can be responsible for
      an increased production of inflammatory mediators. We evaluated remote
      consequences on the gut of lung triggered inflammatory response, neutralizing
      anti-tumor necrosis factor (TNF) antibody was administered to assess the role of
      TNF in lung and gut permeability changes. Rats were anesthetized and ventilated
      for 2 h. A control group (Con: Vt = 10 mL/kg) was compared with a high Vt group
      (HV: Vt = 30 ml/kg). One microCi of I125-labeled human serum albumin was injected
      to measure extravascular albumin space. Gut permeability was evaluated by plasma
      to-lumen ratio leakage of I125 human serum albumin. Extravascular albumin space
      increased in the HV group from 446 +/- 50 microL to 2783 +/- 887 microL. Gut
      index of permeability increased from 5.1 +/- 1.2 to 14.2 +/- 4.9. Anti-TNF
      antibody prevented both lung and gut increase in permeability. High tidal volume
      ventilation resulted in an increase in lung edema and gut permeability,
      antagonism of TNF with neutralizing antibodies abrogated the increase in gut
      permeability as well as lung edema.

PMID- 12785013
TI  - Taurine attenuates calcium-dependent, Fas-mediated neutrophil apoptosis.
AB  - The pathway involved in Fas-mediated neutrophil apoptosis remains to be fully
      elucidated. We examined whether this pathway involved either oxygen-dependent or
      calcium-dependent mechanisms. We also investigated whether taurine, a powerful
      antioxidant and regulator of intracellular calcium fluxes, could inhibit Fas
      mediated neutrophil apoptosis. Neutrophils were stimulated with Fas monoclonal
      antibody in the presence or absence of taurine. Fas receptor ligation resulted in
      significant neutrophil apoptosis at 18 h. Engagement of the Fas receptor rapidly
      resulted in a significant decrease in intracellular calcium. Apoptosis was
      inhibited and intracellular calcium levels were maintained in the presence of
      calcium ionophore A23187 or taurine. Fas ligation did not result in an increase
      in intracellular reactive oxygen species. We have demonstrated that Fas-mediated
      neutrophil apoptosis occurs after a decrease in intracellular calcium and is
      reactive oxygen intermediate independent. Furthermore, the amino acid taurine
      attenuates this pathway of neutrophil apoptosis by calcium regulation. This newly
      identified role of taurine in the inhibition of Fas-mediated neutrophil apoptosis
      may have significant implications for future manipulation of host pro
      inflammatory cell function.

PMID- 12785014
TI  - Cardiac UCP2 expression and myocardial oxidative metabolism during acute septic
      shock in the rat.
AB  - Septic shock decreases cardiac hydraulic work relative to the rate of myocardial
      oxygen consumption, causing decreased mechanical efficiency (hydraulic
      work/myocardial oxygen consumption). This study tested whether the mitochondrial
      uncoupling protein UCP2 was responsible for decreased cardiac mechanical
      efficiency after polymicrobial septic shock. Sepsis was initiated in
      ketamine/xylazine-anesthetized rats by cecal ligation and puncture (CLP). Steady
      state mRNA content was quantified by Northern blot analysis, and protein content
      was estimated by western blot. Additional hearts were removed after 12 h and
      perfused in working mode to measure work (mmHg x mL/min/100 g dry wt) and
      efficiency (CE = work/oxygen consumption, %). The 72-h mortality rate was 80%,
      and deaths occurred between 12-32 h. Cardiac work (152 +/- 15, shock vs. 235 +/-
      16, control; P < 0.05) and cardiac efficiency (4.0 +/- 0.4 vs. 5.6 +/- 0.3; P <
      0.05) were significantly decreased when hearts were isolated 12 h after CLP.
      Myocardial UCP2 mRNA expression was increased by 52% (12 h) compared with control
      hearts; however, there was no detectable UCP2 protein in mitochondria isolated
      from either control or septic hearts. CONCLUSIONS: Although polymicrobial sepsis
      decreased cardiac mechanical efficiency and increased UCP-2 expression coincident
      with premortal hypothermia, we did not detect any evidence of UCP-2 protein in
      septic heart muscle. These data argue against the hypothesis that UCP-2 causes
      decreased cardiac mechanical efficiency in septic shock.

PMID- 12785015
TI  - Neutralization of endotoxin in vitro and in vivo by Bac7(1-35), a proline-rich
      antibacterial peptide.
AB  - Lipopolysaccharides (LPS), or endotoxins, are structural components of gram
      negative bacteria implicated in the pathogenesis of septic shock. In this study
      the antiendotoxin activity of Bac7(1-35), a synthetic peptide based on the
      sequence of a proline-rich antibacterial peptide from bovine neutrophils, was
      investigated in vitro and in an experimental rat model of gram-negative septic
      shock. The ability of Bac7(1-35) to bind LPS from Escherichia coli O111:B4 was
      determined using a sensitive Limulus chromogenic assay. In the in vivo study,
      adult male Wistar rats were given an intraperitoneal injection of 1 x 10(9)
      colony-forming units of E. coli ATCC 25922. All animals were randomized to
      receive intraperitoneally 1 mg/kg Bac7(1-35), or isotonic sodium chloride
      solution (control group C1), 60 mg/kg of piperacillin and 1 mg/kg polymyxin B, 1
      mg/kg of polymyxin B plus 60 mg/kg of piperacillin, and 1 mg/kg of Bac7(1-35)
      plus 60 mg/kg of piperacillin. Each group included 15 animals. Bac7(1-35) was
      found to completely inhibit the LPS procoagulant activity at approximately 10
      microM peptide concentration, as determined by in vitro LAL chromogenic assay.
      Treatment with Bac7(1-35) resulted in significant decrease in plasma endotoxin
      levels and lethality rates compared with saline injected control animals. No
      statistically significant differences were noted between Bac7(1-35) and polymyxin
      B in reducing all variables measured. These results provide evidence for the
      ability of Bac7(1-35) to effectively bind LPS and protect animals from lethal
      effects of this molecule, and point to its potential use for the treatment of
      endotoxin-induced septic shock.

PMID- 12785016
TI  - Suppression of protein kinase Calpha triggers apoptosis through down-regulation
      of Bcl-xL in a rat hepatic epithelial cell line.
AB  - Inactivation of protein kinase C (PKC)alpha plays an important role in modulating
      hepatic failure and/or apoptosis during sepsis. To determine whether and how
      PKCalpha inactivation mediates the apoptosis, PKCalpha was suppressed by
      antisense treatment or transiently transfection in Clone-9 rat hepatic epithelial
      cell line. Apoptosis was evaluated by cell survival rate, poly-adenyl
      ribonuclease polymerase (PARP) cleavage, and terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling
      stain. The expressions of PKCalpha and Bcl-xL were quantified by Western blot
      analysis after antisense treatment. In the transfection studies, cells were co
      transfected with green fluorescent protein cDNA as a transfection marker. The
      expressions of PKCalpha and Bcl-xL were detected by immunohistochemical staining
      with second antibody conjugated with Texas red. Apoptosis was evaluated by
      tetramethyl-rhodamine labeling of DNA strand breaks and immunostaining of 85-kDa
      fragment of PARP. The results showed that cytosolic and membrane-associated
      PKCalpha were decreased by 54.5% and 41.4%, respectively, after PKCalpha
      antisense treatment. The apoptotic incidence and percentage of PARP cleavage were
      significantly increased, whereas protein expression of Bcl-xL was decreased after
      PKCalpha-antisense treatment. In the transfection studies, the results showed
      that most of the cells expressing green fluorescent protein revealed less
      PKCalpha and Bcl-xL protein contents and more in situ PARP cleavage and DNA
      strand breaks. These findings indicated that decrease of PKCalpha declines the
      Bcl-xL content and leads to the vulnerability of apoptosis in hepatic epithelial
      cells. Taken together, our data provide evidence that suppression of PKCalpha
      plays a critical role in triggering caspase-dependent apoptosis, which may act
      through modulating the Bcl-xL expression.

PMID- 12785017
TI  - Ischemic preconditioning reduces intestinal epithelial apoptosis in rats.
AB  - Recent experimental studies have described protective effect of ischemic
      preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We
      hypothesize that to reach a new point of view on the effect of IPC in intestinal
      barrier function, the relationship between I/R-induced mucosal injury and
      apoptosis must first be clarified. The present study was undertaken to
      investigate the role of IPC on intestinal apoptosis and probable contributions of
      bcl-2 expression to this process. We also investigated the effect of intestinal
      IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized
      into four groups each consisting of 11 rats: sham-operated control, I/R group (30
      min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary
      artery occlusion prior before an ischemic insult of 30 min), and IPC alone group
      (10 min of preconditioning). Twenty-four hours later, ileum samples were
      obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/-
      18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/-
      13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was
      significantly lower in IPC-I/R group than that of I/R group, and these findings
      were further supported by DNA laddering and M30 findings. Diminished bcl-2
      expression observed in the ileal specimens of I/R group was prevented by IPC. Our
      results indicate that IPC may provide a protective effect on ileal epithelium and
      that this effect is probably the result of a significant increase in the
      expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help
      preserving the vitality of intestinal structures that have a critical function,
      cessation of which often leads to multiorgan dysfunction syndrome.

PMID- 12785018
TI  - Relation between coronary artery disease, risk factors and intima-media thickness
      of carotid artery, arterial distensibility, and stiffness index.
AB  - Atherosclerosis is a diffuse process that involves vessel structures. In recent
      years, the relation of noninvasive parameters such as intima-media thickening
      (IMT), arterial distensibility (AD), and stiffness index (SI) to cardiovascular
      diseases has been researched. However, we have not found any study that has
      included all these parameters. The aim of this study is to examine the relation
      between the presence of coronary artery disease (CAD) and its risk factors to AD,
      SI, and IMT, which are the noninvasive predictors of atherosclerotic process in
      the carotid artery. Included in the study were 180 patients who were diagnosed as
      having CAD by coronary angiography (those with at least > or = 30% stenosis in
      the coronary arteries) and, as a control group, 53 persons who had normal
      appearing coronary angiographies. IMT, AD, and SI values of all the patients in
      the study were measured by echo-Doppler imaging (AD formula = 2 x (AoS - AoD)/PP
      x AoD, SI formula = (SBP/DBP)/([AoS - AoD]/AoD). Significantly increased IMT
      (0.82 +/- 0.1, 0.57 +/- 0.1, p<0.05), decreased AD (0.25 +/- 0.9, 0.37 +/- 0.1,
      p<0.05), and increased SI (13 +/- 4, 8 +/- 3, p<0.05) values were detected in the
      CAD group compared to the control group. A significant correlation was found
      between IMT and presence of diabetes mellitus (DM), systolic blood pressure,
      total cholesterol, and presence of plaque in carotids, and age. In the coronary
      artery disease group there was a significant correlation between AD and age,
      systolic blood pressure, and HDL cholesterol levels, while there was no
      significant correlation with plaque development. A significant correlation was
      also found between stiffness index and systolic blood pressure and age; however,
      there was no relation between number of involved vessels and IMT, AD, and SI. We
      found sensitivity, specificity, and positive predictive and negative predictive
      values for CAD diagnosis to be 70%, 75%, 77%, and 66%, respectively. In CAD
      cases, according to data in this study, IMT and SI increased while AD decreased,
      and this was detected by carotid artery Doppler ultrasonography. Therefore, it
      was concluded that these cheaper, noninvasive, and easily available parameters
      could be used in early diagnosis of CAD.

PMID- 12785019
TI  - HIV-associated coronary artery disease.
AB  - Cases, case series, and related articles on coronary artery disease in patients
      with human immunodeficiency virus (HIV) infection and acquired immunodeficiency
      syndrome (AIDS) identified through a comprehensive literature search were
      examined for clinical characteristics and angiographic findings of HIV-associated
      coronary artery disease. Among 129 identified cases, 91% were males. The mean age
      was 42.3 +/- 10.2 (SD) years (range, 23 to 77 years). The interval between the
      diagnosis of HIV infection and the diagnosis of coronary artery disease was 72 +/
      60 (SD) months. Degree of immunosuppression was variable (CD4 mean, 313 +/- 209
      cells/mm3; range, 6-1070 cells/mm3). There was no correlation between the CD4
      cell count and the development and progression of coronary artery disease.
      Similarly, the development and progression of coronary artery disease was
      independent of the presence of HIV-related opportunistic infections. Acute
      myocardial infarction was the initial presentation in 77% of patients. In 76
      patients, information on diseased vessels was available: 36 (47%) patients had 3
      vessel disease, 14 (18%) patients had 2-vessel disease, and 26 patients (35%) had
      1-vessel disease. The left anterior descending artery was involved in 47 (62%)
      patients while the left circumflex and right coronary arteries were involved in
      34 (45%) and 38 (50%) patients, respectively. Thirty-two (25%) patients underwent
      catheter-based or surgical revascularization. Data were not adequate to assess
      the prognosis following the acute coronary events or revascularization. The
      histologic characteristics unique to HIV-associated coronary arteriopathy were
      diffuse circumferential involvement of the vessel with an unusual proliferation
      of smooth muscle cells, mixed with abundant elastic fibers, resulting in
      endoluminal protrusions. Coronary artery disease was a late complication of AIDS.

PMID- 12785020
TI  - Clinical evaluation of coronary lesion characteristics in acute myocardial
      infarction.
AB  - Coronary lesion instability at the onset of acute myocardial infarction (AMI) was
      evaluated. The mechanism of AMI has been considered to be coronary lesion
      instability with occlusive thrombus, although more than one half of AMI occurs in
      clinically stable patients. A total of 313 AMI patients treated by primary
      percutaneous transluminal coronary angioplasty with provisional stenting (rate,
      41%) were studied. They were divided into 2 groups: group 1A (n = 211), without
      unstable angina before AMI onset, and group 1B (n = 102), with unstable angina
      before onset. Moreover, angina patients treated similarly were studied: group 2A
      (n = 180), with stable angina, and group 2B (n = 204), with unstable angina.
      Coronary lesion instability at AMI onset was also predicted by C-reactive protein
      (CRP) levels within 6 hours after onset, before they were affected by myocardial
      damage. The incidence of repeated AMI and/or target vessel revascularization was
      1.9% in group 1A, 7.8% in 1B (p=0.035), 1.7% in 2A, and 5.9% in 2B (p=0.043).
      Event-free survival curves were consistent with each other in groups 1A and 2A
      and in groups 1B and 2B. CRP levels on admission were 2.0 +/- 1.7 mg/L in group
      1A, 3.3 +/- 4.8 mg/L in group 1B (p<0.001), 2.1 +/- 1.7 mg/L in group 2A, and 3.4
      +/- 4.7 mg/L in group 2B (p<0.001). Thus coronary lesion characteristics at AMI
      onset appeared to be similar in groups 1A and 2A and in groups 1B and 2B. A
      substantial number of patients have stable culprit lesions at the onset of AMI.

PMID- 12785021
TI  - The importance of von Willebrand factor level and heart rate changes in acute
      coronary syndromes: a comparison with chronic ischemic conditions.
AB  - The pathogenesis of acute coronary syndrome (ACS) and transient myocardial
      ischemia (TMI) is not completely understood. Therefore, the authors studied the
      biological indicators of thrombogenesis and sympathetic activity. The study was
      conducted on 50 patients with acute coronary syndrome and 30 patients with stable
      angina pectoris. Treatment was standardized with low-molecular-weight heparin and
      300 mg aspirin/day but with no IIb/IIIa inhibitors, an oral beta-blocker,
      diltiazem 60 mg tid, glyceryl trinitrate i.v. in patients with ACS but with
      mononitrates orally and low-molecular-weight heparin in patients with stable
      angina. Twenty-four-hour continuous ECG monitoring and ST segment analysis were
      performed on day 2 of admission and heart rate analysis was performed 10, 5, and
      1 minute before and during the myocardial ischemia periods. Blood sampling for
      von Willebrand factor (vWf) determination was performed through a peripheral vein
      at 8 AM, noon, 6 PM and 10 PM and half an hour after the description of angina.
      The patients with ACS were grouped as transient myocardial ischemia positive (n =
      20) and negative (n = 30). The patients with stable angina were designated as the
      control group (n = 30). The detected vWf levels at 4 different daytime periods in
      patients with ACS were significantly higher than those in patients with stable
      angina. At the 6 PM to 10 PM period, the vWf level increase was significantly
      higher in patients with TMI than in the patients without TMI. At the 8 AM to noon
      period, the detected vWf levels decreased significantly in both TMI groups.
      During the nocturnal ischemia periods, the increase in vWf levels immediately
      after angina was significantly more apparent than the detected changes during
      daytime ischemia. Analysis showed that heart rates before the ischemia during
      stable angina episodes were significantly higher than those in TMI (-) (silent)
      angina. The heart rate difference between 10 minutes before and during the
      ischemia in the angina group was significantly different from that during TMI (-)
      (silent) ischemia. The heart rates at the times related to ischemia in the
      nocturnal period were significantly lower than those in the daytime period. The
      heart rate differences between the ischemia-related times and during the ischemia
      were significantly higher in daytime ischemic attacks than in nocturnal ischemic
      attacks. The study confirms that the vWf level, which is an indicator of
      thrombogenesis, was significantly increased in patients with ACS. Nocturnal
      ischemia is associated with thrombogenesis. Daytime ischemia is associated with
      increased sympathetic activity, and symptomatic ischemia is usually associated
      with increased sympathetic activity.

PMID- 12785022
TI  - A review of the concept of circulatory bioassist focused on the "new" demand
      dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?
AB  - After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation
      owing to the poor long-term results, caused by the muscular degeneration
      subsequent to chronic continuous electrical stimulation of the latissimus dorsi.
      An activity-rest stimulation protocol that avoids full transformation of the
      skeletal muscle, maintaining muscular properties over time, has been successfully
      tried. This "demand" stimulation protocol showed in humans good results improving
      NYHA class, ejection fraction value, and survival. The discussion about the
      capability of this and a unique kind of cardiocirculatory bioassist is due to be
      reopened. In fact, heart transplant, percutaneous circulatory-supporting device,
      multisites stimulation therapy, and total artificial heart have some drawbacks,
      one of which is the economic cost. In developing countries the more economic
      demand dynamic cardiomyoplasty may still play a role.

PMID- 12785023
TI  - Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose
      veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).
AB  - The study compared, by a prospective, randomized method, 6 treatment options: A:
      Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab
      avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy.
      Results were analyzed 10 years after inclusion and initial treatment. Endpoints
      of the study were variations in ambulatory venous pressure (AVP), refilling time
      (RT), presence of duplex-reflux, and number of recurrent or new incompetent
      venous sites. The number of patients, limbs, and treated venous segments were
      comparable in the 6 treatment groups, also comparable for age and sex
      distribution. The occurrence of new varicose veins at 5 years varied from 34% for
      group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group
      (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins
      varied from 37% in F to 56% in A. At inclusion AVP was comparable in the
      different groups. At 10 years the decrease in AVP and the increase in RT
      (indicating decrease in reflux), was generally comparable in the different
      groups. Also at 10 years the number of new points of major incompetence was
      comparable in all treatment groups. These results indicate that, when correctly
      performed, all treatments may be similarly effective. "Standard," low-dose
      sclerotherapy appears to be less effective than high-dose sclero and foam
      sclerotherapy which may obtain, in selected subjects, results comparable to
      surgery.

PMID- 12785024
TI  - 8-Epi-PGF2alpha and 6-oxo-PGF1alpha in human (varicose) veins: influence of age,
      sex, and risk factors.
AB  - The isoprostane 8-epi PGF2alpha is a vasoconstrictive, mitogenic, proliferative,
      and mild proaggregatory agent. We examined 8-epi-PGF2alpha and 6-oxo-PGF1alpha
      from venous tissue derived from varicose (venous) surgery by means of a specific
      radioimmunoassay. A total of 336 samples from 82 patients (50 females, 32 males;
      aged 22-68 years) were examined. Tissue samples were classified according to
      normal, dilated, and varicose. Of these, 94 samples from 31 patients (20 females,
      11 males; aged 29-64 years) with additional risk factors (cigarette smoking,
      hyperlipidemia, diabetes mellitus) were determined in the same way. Mean absolute
      values for 6-oxo-PGF1alpha are not significantly higher for dilated segments
      followed by varicose and intact samples. No significant age and sex differences
      can be monitored. Presence of risk factors, however, results in a significantly
      diminished 6-oxo-PGF1alpha, irrespective of morphology. 8-Epi-PGF2alpha again
      showed no age and sex dependence, its presence in varicose segments, however, was
      significantly (p<0.01) decreased. Risk factors resulted in a significantly
      increased 8-epi-PGF2alpha. These data indicate that the influence of risk factors
      on vasomodulatory (iso-)eicosanoids of human veins is more pronounced than the
      actual morphologic stage. Lower 8-epi-PGF2alpha in varicose veins may shift the
      venous tone toward vasodilatation and contribute to development and progression
      of varicosis.

PMID- 12785025
TI  - Improvement of microcirculation and healing of venous hypertension and ulcers
      with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A
      prospective-randomized-controlled study.
AB  - In 20 patients with chronic venous insufficiency and venous hypertension
      associated with ulcerations, the effects of a new compound, applied onto the skin
      (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was
      used to assess the presence of venous obstruction and incompetence, and
      microcirculatory methods were used to assess and quantify venous microangiopathy
      and to follow up subjects after local treatment with Crystacide. Laser Doppler
      flowmetry (LDF) was used to assess skin perfusion in association with
      transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma
      free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with
      the D-Rom test. Crystacide was applied around and on the ulcer for 10 days.
      Crystacide was more effective than the control treatment: PO2 was increased, PFR
      and LDF were decreased (flux increase is associated with venous hypertension),
      and the ulcer area was significantly smaller at 10 days in the Crystacide group
      in comparison with the placebo group (p<0.05). In conclusion, in venous
      ulcerations, local treatment with Crystacide (10 days) improves the
      microcirculation and decreases skin free radicals improving healing.

PMID- 12785026
TI  - Prevalence and risk factors of peripheral arterial obstructive disease in
      Taiwanese type 2 diabetic patients.
AB  - The aim of this study was to evaluate the prevalence and risk factors of
      peripheral arterial obstructive disease (PAD) in Taiwanese type 2 diabetic
      patients. A total of 610 patients (268 men and 342 women), aged 63.3 +/- 10.8
      years, were recruited from a diabetic clinic in a teaching hospital. PAD was
      diagnosed by an ankle-brachial index (ABI) < 0.9 on either leg. Risk factors
      studied were age, sex, body mass index (BMI), smoking, diabetes duration,
      hypertension, insulin therapy, systolic blood pressure (SBP), diastolic blood
      pressure (DBP), fasting plasma glucose (FPG), serum total cholesterol (TC), and
      triglyceride (TG). Overall prevalence of PAD was 10.0% without significant sexual
      difference. Univariate analyses disclosed age, BMI (inverse association),
      diabetes duration, hypertension, insulin therapy, and SBP as significant risk
      factors. In stepwise logistic regression, age, SBP, BMI, and insulin therapy were
      independent risk factors with respective odds ratios (95% confidence intervals,
      CI) of 1.09 (1.05-1.13), 1.02 (1.01-1.04), 0.88 (0.80-0.96), and 3.37 (1.83
      6.19). In conclusion, prevalence of PAD in Taiwanese type 2 diabetic patients was
      10.0% and the major risk factors were older age, lower BMI, higher SBP, and
      insulin therapy. The inverse association between PAD and BMI is contradictory to
      the general impression that obesity is a risk factor for PAD.

PMID- 12785027
TI  - Inflammatory diseases associated with Takayasu's arteritis.
AB  - The etiology of Takayasu's arteritis is unknown; however, abnormality of the
      immune system plays an important role. To clarify a possible association between
      inflammatory diseases and Takayasu's arteritis, the authors retrospectively
      reviewed the medical records of 36 patients (2 men and 34 women), admitted to
      their department with this diagnosis. They found that 11 of the 36 patients had
      at least 1 other chronic or subacute inflammatory disease: Chronic tonsillitis,
      tuberculous lymphadenitis of the neck, chronic hepatitis B (infectious diseases);
      pyoderma gangrenosum, erythema nodosum (skin lesions); subacute thyroiditis,
      chronic thyroiditis (autoimmune diseases); Crohn disease, and ulcerative colitis
      (inflammatory diseases with unknown etiology). The present observation revealed a
      high prevalence of other inflammatory diseases in patients with Takayasu's
      arteritis and raises the possibility that Takayasu's arteritis may be associated
      with abnormality of the immune system activated by other inflammatory diseases,
      such as infection, autoimmune diseases, or inflammatory diseases of unknown
      origin.

PMID- 12785028
TI  - Evaluation of regional aortic distensibility using color kinesis.
AB  - Regional aortic stiffness cannot be evaluated by conventional methods. Regional
      aortic wall velocity during systole in the descending aorta was evaluated by
      using transesophageal echocardiography with color kinesis. The authors defined
      regional aortic distensibility (RAD) by considering pulse pressure, with RAD
      (microm/s/mm Hg) = (regional aortic wall velocity)/(pulse pressure). RAD was
      evaluated in 38 patients who had coronary artery disease (CAD) and 10 who did
      not. RAD decreased depending on aging (partial regression coefficient was -5.39 x
      10(-1), p<0.001), and RAD was lower in the CAD group than that in the no-CAD
      group (p<0.05). In the CAD group, 19 patients had a single fixed plaque (4
      calcified and 15 noncalcified plaques). RAD in the calcified plaque was lower
      than that in the noncalcified plaque (p<0.01), and RAD was lower in the
      noncalcified plaque than that in the no-plaque region (p<0.05). In noncalcified
      plaques, the relation between RAD and maximum intimal thickness had a significant
      correlation, r=0.7, p<0.001. The residual of RAD from the regression line was
      significantly larger in the calcified plaque than that in the noncalcified plaque
      (p<0.001). In conclusion, RAD can express increasing regional aortic wall
      stiffness brought about by arteriosclerosis quantitatively. Color kinesis
      provides information on characteristic difference between calcified and
      noncalcified plaque.

PMID- 12785029
TI  - False coronary lumen originating from left main coronary artery dissection
      causing acute myocardial infarction--a case report.
AB  - Spontaneous coronary artery dissection is a rare cause of acute myocardial
      infarction, which is infrequently diagnosed antemortem. The majority of the
      previously reported cases were found in women of whom a significant proportion
      presented during pregnancy or the postpartum period. A case is presented of an
      acute myocardial infarction in a 37-year-old woman, unrelated to pregnancy or the
      postpartum state, with an unusual spontaneous coronary dissection that was
      angiographically documented 6 days after thrombolytic therapy. Originating in a
      small dissection in the left main coronary artery, a false lumen parallel to the
      left anterior descending coronary artery (LAD) with a separation of the lumina of
      up to 1 mm was found with a reentry of the false lumen into the LAD in its mid
      portion. Both lumina were perfused and the true lumen of the LAD showed a 50% to
      60% diameter stenosis. Because no signs of ongoing ischemia could be detected at
      rest or during exercise, the patient was treated medically. Two months later,
      repeat coronary angiography documented a complete obliteration of the false lumen
      with moderate stenosis of the proximal LAD. Pathophysiologic aspects and
      treatment options of spontaneous coronary artery dissections are discussed.

PMID- 12785030
TI  - Myocardial contusion culminating in a ruptured pseudoaneurysm of the left
      ventricle--a case report.
AB  - Blunt chest trauma continues to be one of the most common injuries at all ages.
      Trauma in general is the leading cause of death in the young to middle-aged
      segment of our population. Blunt chest injury is said to occur in more than one
      third of all motor vehicle accidents. Myocardial contusion is the most frequent
      cardiac injury resulting from blunt chest trauma. Autopsy studies indicate that
      cardiac trauma was directly associated with death in approximately 10% of cases
      suffering blunt chest injury. Aneurysm formation as a sequela of blunt cardiac
      trauma is a rare entity and pseudoaneurysm formation is considerably more rare. A
      case of myocardial contusion resulting in myocardial necrosis, rupture of the
      ventricle, and pseudoaneurysm formation with subsequent rupture and sudden death
      is presented.

PMID- 12785031
TI  - Correction of AV-nodal block in a 27-year-old man with severe obstructive sleep
      apnea--a case report.
AB  - A 27-year-old morbidly obese man diagnosed with severe obstructive sleep apnea
      (OSA) and experiencing significant ventricular asystoles at times exceeding 8
      seconds, during polysomnography. The bradyarrhythmias were successfully corrected
      with the application of a nasal continuous positive airway pressure (CPAP) mask.
      Follow-up 24-hour ambulatory Holter monitoring without the aid of a nasal CPAP
      mask and repeat polysomnography with a CPAP mask after several weeks of
      continuous CPAP therapy during sleep revealed no evidence of ventricular
      asystole, despite no change in the patient's body mass index. We discuss several
      mechanisms explaining the findings in this particular patient.

PMID- 12785032
TI  - Adenosine-sensitive wide-complex tachycardia: an uncommon variant of idiopathic
      fascicular ventricular tachycardia--a case report.
AB  - Most wide-complex tachycardias encountered in the emergency department (ED) are
      ventricular in origin, most commonly associated with structural heart disease.
      Ventricular tachyarrhythmias range in severity from life-threatening rhythms (eg,
      ventricular fibrillation and hemodynamically compromising ventricular tachycardia
      [VT]) to idiopathic forms of VT, which have a benign clinical course and a more
      favorable prognosis. The authors present the case of a 34-year-old woman who
      presented to the ED, with a wide-complex tachycardia with a right-bundle-branch
      block (RBBB) morphology and a right inferior axis, which was terminated with
      adenosine. The patient was previously misdiagnosed as suffering from a paroxysmal
      supraventricular tachycardia (SVT), which was unresponsive to beta-blocker
      therapy. Although the tachycardia responded to adenosine, suggestive of an SVT,
      the patient was referred to the arrhythmia service, where further work-up
      revealed an uncommon form of an idiopathic VT, originating from the left anterior
      fascicle. The authors discuss the unique electrocardiographic and
      electrophysiologic properties and useful diagnostic maneuvers required to
      properly identify this form of VT.

PMID- 12785033
TI  - Apical hypertrophic cardiomyopathy: diagnosis with contrast-enhanced
      echocardiography--a case report.
AB  - Apical hypertrophic cardiomyopathy is a rare form of hypertrophic cardiomyopathy
      (HCM) recognized by a unique spadelike configuration on the left ventriculogram.
      Two-dimensional echocardiography is another useful tool in the diagnosis of this
      condition. The diagnosis may be difficult and may mimic akinesia or apical
      thrombus in some patients with poor acoustic windows. A 50-year-old woman with
      typical angina and left ventricular hypertrophy with T wave inversion in leads V3
      V6, II, III and aVF is presented. Apical HCM was diagnosed with contrast-enhanced
      echocardiography and confirmed by finding a spadelike configuration on the left
      ventriculogram. Apical HCM should be considered in patients in whom symptoms and
      ECG findings mimic ischemic heart disease. Contrast-enhanced echocardiography is
      a reliable and simple method in the diagnosis of apical HCM.

PMID- 12785034
TI  - Deficiency of protein S-mediated familial venous thrombophilia--a case report.
AB  - Deficiency of protein S causes potential problems of thrombosis. Cases of
      familial venous thrombosis due to deficiency of protein S were presented. First,
      an 85-year-old woman had pulmonary thromboembolism due to left deep femoral
      venous thrombosis, which might be triggered by leg fracture and the long-term
      treatment with a plaster cast. Next, her 29-year-old granddaughter had episodes
      of recurrent venous thrombosis in her legs and arms, which might be triggered by
      the treatment with a plaster cast and abortion. In the latter part, the aspects
      of risks for thromboembolism, potential problems in gestational period, and an
      advisability of thromboprophylaxis in patients with deficiency of protein S are
      described.

PMID- 12785035
TI  - Do some genetic mutations predict the development of dilated cardiomyopathy in
      patients with Becker's muscular dystrophy?

PMID- 12785036
TI  - Neuropathic pain.

PMID- 12785037
TI  - More patients served by hospice, but still a last resort.

PMID- 12785038
TI  - Chronic obstructive pulmonary disease and dyspnea: a Pandora's box of comorbid
      symptoms?

PMID- 12785039
TI  - Comparison of hospice use and demographics among European Americans, African
      Americans, and Latinos.
AB  - The goals of this study were to compare the rate of use of hospice services and
      other relevant characteristics of European American, African American, and Latino
      hospice patients. Information on length of stay in hospice, marital status, age,
      disposition at termination, living situation, caregiver, referral source, and
      payment method was collected on patients who used hospice care in southern New
      Jersey between the years 1995 and 2001 (N = 1958). African Americans and Latinos
      were both found to use services at significantly lower rates than European
      Americans. In addition, African American use of hospice declined significantly
      during this time period, while European American use increased. Differences were
      also found among the groups in marital status, living situation, caregiver,
      referral source, and payment method. These differences highlight the need for
      hospice providers to recognize issues unique to minority groups. The reasons for
      these disparities need to be clarified by further research.

PMID- 12785040
TI  - Characteristics of dementia end-of-life care across care settings.
AB  - End-of-life care for persons with dementia in different care settings was
      retrospectively surveyed. In this sample, care recipients receiving hospice care
      and pain control stayed at home longer and were more likely to die at home.
      Psychiatric symptoms increased caregiver burden and were the most common reason
      for admission to an institution, and psychiatric care was associated with longer
      stay at home. Presence of advance directives decreased hospital stay and
      increased the likelihood of dying in a nursing home. Care recipients dying at
      home had fewer symptoms and less discomfort than care recipients dying in other
      settings. These results indicate that quality end-of-life care can be provided at
      home and is facilitated by hospice programs, effective pain control, and
      psychiatric care.

PMID- 12785041
TI  - Developing end-of-life interdisciplinary programs in universitywide settings.
AB  - Interdisciplinary programs in end of life are widely discussed as valuable,
      particularly approaches to end-of-life care. Despite this emphasis,
      interdisciplinary programs have not been easy to implement. In universities, the
      implementation of interdisciplinary programs encounters administrative obstacles,
      including credit for the time spent in these group efforts and "ownership" of
      interdisciplinary courses (IDCs). This article details the process of development
      and the activities of an end-of-life interdisciplinary program at one urban
      university with a major medical center. The issues faced in the first year are
      examined. These included trust, group identity, and communication. The lessons
      from the first-year activities are presented and efforts of the second year
      described.

PMID- 12785042
TI  - Caregivers' satisfaction with hospice care in the last 24 hours of life.
AB  - The goals of this study were to identify elements of care that contributed to
      positive and negative perceptions of hospice care in the last 24 hours of life,
      and to define patient and family characteristics that are associated with
      satisfaction with care during this difficult period. Surveys were sent to 207
      primary caregivers, and 112 surveys were returned. This study reports four
      findings that elucidate the factors that make family members more or less
      satisfied with the care that their loved one received during the last day of
      life, and how satisfaction with this period of care should be measured.

PMID- 12785043
TI  - The RAI-PC: an assessment instrument for palliative care in all settings.
AB  - Large numbers of persons in most types of healthcare settings have palliative
      care needs that have considerable impact on their quality of life. Therefore,
      InterRAI, a multinational consortium of researchers, clinicians, and regulators
      that uses assessment systems to improve the care of elderly and disabled persons,
      designed a standardized assessment tool, the Resident Assessment Instrument for
      Palliative Care (RAI-PC). The RAI-PC can be used for both the design of
      individual care plans and for case mix and outcomes research. Some elements of
      this instrument are taken from the resident assessment instrument (RAI) mandated
      for use in all nursing homes in the United States and widely used throughout the
      world. The RAI-PC can be used alone or in counjunction with the other assessment
      tools designed by the InterRAI collaboration: the RAI for homecare (RAI-HC), for
      acute care (RAI-AC), and for mental health care (RAI-MH). The objective of this
      study was to field test and carry out reliability studies on the RAI-PC. After
      appropriate approvals were obtained, the RAI-PC instrument was field tested on
      151 persons in three countries in more than five types of settings. Data obtained
      from 144 of these individuals were analyzed for reliability. The reliability of
      the instrument was very good, with about 50 percent of the questions having kappa
      values of 0.8 or higher, and the average kappa value for each of the eight
      domains ranging from 0.76 to 0.95. The 54 men and 95 women had a mean age of 79
      years. Thirty-four percent of individuals suffered pain daily. Eighty percent
      tired easily; 52 percent were breathless on exertion; and 19 to 53 percent had
      one or more other symptoms, including change in sleep pattern, dry mouth, nausea
      and vomiting, anorexia, breathlessness at rest, constipation, and diarrhea. The
      number of symptoms an individual reported increased as the estimated time until
      death declined. The "clinician friendly" RAI-PC can be used in multiple sites of
      care to facilitate both care planning and case mix and outcomes research.

PMID- 12785044
TI  - Integrating complementary and alternative medicine (CAM) into standard hospice
      and palliative care.
AB  - In the United States, there are 629 million visits to complementary and
      alternative medicine (CAM) providers each year. Many adults appear to value both
      conventional and CAM approaches. Because of this public interest and promising
      evidence that CAM relieves suffering and improves quality of life, we established
      a program of CAM, known as Integrative Palliative Care (IPC), in a US hospice.
      This paper outlines our strategy of collaborative relationships with community
      schools of traditional Chinese medicine (TCM), massage, and harp therapy. It also
      describes the use of volunteers and small grants and donations to develop and
      maintain a program of CAM in the hospice setting. The difficulties of research
      design, problems with tracking outcomes, and the shortcomings of providing
      therapies with this model are discussed.

PMID- 12785045
TI  - Breakthrough strong opioid analgesia prescription in patients using transdermal
      fentanyl admitted to a hospice.
AB  - Durogesic (fentanyl) patches have revolutionized pain relief, but patients still
      require breakthrough medication. A retrospective analysis of in-patient admission
      notes at a 25-bed hospice over a six-month period was carried out. Details of
      analgesia being used on admission for both background and breakthrough pain were
      obtained, and the appropriateness of the breakthrough dose for those patients
      using transdermal fentanyl was determined. During the study period 278 patients
      were admitted to the hospice and 56 (20 percent) were using transdermal fentanyl.
      Of these, 35 (62 percent) were prescribed strong opioid analgesia--the dose of
      breakthrough medication prescribed was appropriate in 11 patients (31 percent).
      Rescue dosing was less than recommended, in relation to prescribed transdermal
      fentanyl strength in 21 patients (60 percent) and greater than recommended in one
      patient (3 percent). In this study, short-acting strong opioid analgesia was not
      always prescribed for patients using transdermal fentanyl, and when they were
      prescribed, this was in the appropriate dose range in less than a third of
      patients.

PMID- 12785046
TI  - The Hawthorne effect in the assessment of pain by house staff.
AB  - Internal medicine residents are one component of the healthcare delivery team in
      the hospital setting. Their ability to assess and treat pain should be considered
      in quality improvement efforts. We surveyed our residents, using a 0 to 10 scale
      to determine how well they assessed their patients' level of pain. We then asked
      half of these residents to write down their patients' pain score as a fifth vital
      sign in the medical record. We repeated the house staff survey three weeks later.
      The residents improved their assessment as a whole, with the nonintervention
      group faring better on the follow-up surveys. We believe that the residents'
      improvement can be attributed to the Hawthorne effect, in which a group that is
      singled out for special study or consideration has its performance positively
      affected. The residents' ability to accurately rate patients with moderate and
      severe pain is still an area for further development. Improvements in our
      palliative care curriculum have been implemented to enhance our residents'
      education and performance in this area.

PMID- 12785047
TI  - When dying at home was a crime.

PMID- 12785048
TI  - Structural studies of bleached melanin by synchrotron small-angle X-ray
      scattering.
AB  - Small-angle X-ray scattering was used to measure the effects of chemical
      bleaching on the size and morphology of tyrosine-derived synthetic melanin
      dispersed in aqueous media. The average size as measured by the radius of
      gyration of the melanin particles in solution, at neutral to mildly basic pH,
      decreases from 16.5 to 12.5 angstroms with increased bleaching. The melanin
      particles exhibit scattering characteristic of sheet-like structures with a
      thickness of approximately 11 angstroms at all but the highest levels of
      bleaching. The scattering data are well described by the form factor for
      scattering from a pancake-like circular cylinder. These data are consistent with
      the hypothesis that unbleached melanin, at neutral to mildly basic pH, is a
      planar aggregate of 6- to 10-nm-sized melanin protomolecules, hydrogen bonded
      through their quinone and phenolic perimeters. The observed decrease in melanin
      particle size with increased bleaching is interpreted as evidence for
      deaggregation, most probably the result of oxidative disruption of hydrogen bonds
      and an increase in the number of charged, carboxylic acid groups, whereby the
      melanin aggregates disassociate into units composed of decreasing numbers of
      protomolecules.

PMID- 12785049
TI  - Photochemistry and photophysics of thienocarbazoles.
AB  - Two methylated thienocarbazoles and two of their synthetic nitro-precursors have
      been examined by absorption, luminescence, laser flash photolysis and
      photoacoustic techniques. Their spectroscopic and photophysical characterization
      involves fluorescence spectra, fluorescence quantum yields and lifetimes, and
      phosphorescence spectra and phosphorescence lifetimes for all the compounds.
      Triplet-singlet difference absorption spectra, triplet molar absorption
      coefficients, triplet lifetimes, intersystem crossing S1 --> T1 and singlet
      molecular oxygen yields were obtained for the thienocarbazoles. In the case of
      the thienocarbazoles it was found that the lowest-lying singlet and triplet
      excited states, S1 and T1, are of pi,pi* origin, whereas for their precursors S1
      is n,pi*, and T1 is pi,pi*. In both thienocarbazoles it appears that the
      thianaphthene ring dictates the S1 --> T1 yield, albeit there is less
      predominance of that ring in the triplet state of the linear thienocarbazole,
      which leads to a decrease in the observed phiT value.

PMID- 12785050
TI  - Photoaffinity labeling of the N-methyltransferase domains of cyclosporin
      synthetase.
AB  - The multifunctional polypeptide cyclosporin synthetase (CySyn) remains one of the
      most complex nonribosomal peptide synthetase described. In this study we used a
      highly specific photoaffinity labeling procedure with the natural cofactor S
      adenosyl-L-methionine (AdoMet), 14C-isotopically labeled at the Sdelta methyl
      group to probe the concerted AdoMet-binding interaction of the N
      methyltransferase (N-MTase) centers of CySyn. The binding stoichiometry for the
      enzyme-AdoMet complex was determined to be 1:7, which is in agreement with
      inferences made from analysis of the complementary DNA sequence of the simA gene
      encoding the CySyn polypeptide. The photolabeling of the AdoMet-binding sites
      displayed homotropic negative cooperativity, characterized by a curvilinear
      Scatchard plot with upward concavity. Although, the process of N-methyl transfer
      is not a critical event for peptide elongation, the destabilizing homotropic
      interactions between N-MTase centers that were observed may represent a mechanism
      whereby the enzyme preserves the proficiency of the substrate-channeling process
      of cyclosporin peptide assembly over a broad range of cofactor concentrations.
      Furthermore, we demonstrated the utility of the photolabeling procedure for
      tracking the enzyme during purification.

PMID- 12785051
TI  - A monomethine cyanine dye Cyan 40 for two-photon-excited fluorescence detection
      of nucleic acids and their visualization in live cells.
AB  - Monomethine cyanine dye 4-((1-methylbenzothiazolyliliden-2)methyl)-1,2,6
      trimethylpyridinium perchlorate (Cyan 40) was investigated as a two-photon
      excited fluorescence probe for nucleic acids (NA). Cyan 40 has been shown to
      demonstrate efficient two-photon-excited fluorescence in the presence of NA in
      vitro in contrast to solutions without NA. Two-photon confocal laser scanning
      microscopy (TPCLSM) and two-photon laser scanning microspectrofluorometry were
      used to check the possibility of using Cyan 40 as two-photon-excited fluorescence
      label for NA in living cells. Study of dye effect on viability of cells was also
      carried out. We ascertained that Cyan 40 is a cell-permeant dye, manifesting
      efficient two-photon-excited fluorescence when bound to NA in living cells,
      without any significant influence on viability of cells. TPCLSM images obtained
      from stained cells indicate preferential RNA staining by Cyan 40 compared with
      DNA.

PMID- 12785052
TI  - In vitro cis-trans photoisomerization of palythene and usujirene. Implications on
      the in vivo transformation of mycosporine-like amino acids.
AB  - The in vitro photoinduced reactions of the mycosporine-like amino acids (MAA)
      usujirene and palythene were studied by monochromatic stationary irradiation at
      366 nm. High-performance liquid chromatography analysis of the irradiated aqueous
      solution of usujirene indicated a low photoreactivity on the basis of the
      observed photodecomposition quantum yield of phi(-U) = (2.86 +/- 0.80) x 10(-5),
      which can be partially accounted for by the cis-trans photoisomerization of
      usujirene to palythene (phi(U-->P) = [1.71 +/- 0.13] x 10(-5)). However,
      palythene in aqueous solution showed a higher photostability than did usujirene
      under equivalent conditions, establishing a photostationary mixture of cis-trans
      isomers with a relative composition of palythene-usujirene (11:1). These results
      may explain the preferential in vivo accumulation of palythene relative to that
      of usujirene observed in several dinoflagellate species.

PMID- 12785053
TI  - Picosecond dynamics of a peptide from the acetylcholine receptor interacting with
      a neurotoxin probed by tailored tryptophan fluorescence.
AB  - A tryptophan analog, dehydro-N-acetyl-L-tryptophanamide (delta-NATA), which is
      produced enzymatically via L-tryptophan 2',3'-oxidase from Chromobacterium
      violaceum, is newly used for time-resolved fluorescence. The absorption and
      emission maxima of delta-NATA at 332 and 417 nm, respectively, in 20%
      dimethylformamide-water are significantly shifted to the red with respect to
      those of tryptophan in water, permitting us to measure its fluorescence in the
      presence of tryptophan residues. We demonstrate that the steady-state spectra and
      the fluorescence decay of delta-NATA are very sensitive to environment, changing
      dramatically with solvent as the chromophore is localized within a protein and
      when this tagged protein binds to a peptide. The tryptophan oxidase was also used
      to modify the single Trp of a neurotoxin from snake (Naja nigricollis) venom.
      Modification of the toxin alpha (dehydrotryptophan-toxin alpha) permitted its
      investigation in complex with a synthetic 15-amino acid peptide corresponding to
      a loop of the agonist-binding site of acetylcholine receptor (AchR) from Torpedo
      marmorata species. The peptide alpha-185 possesses a single Trp at the third
      position (Trp187 of AchR) and a disulfide bridge between Cys192 and Cys193. A
      single-exponential rotational diffusion time with a constant of 1.65 ns is
      measured for the isolated 15-amino acid peptide. This suggests that Trp motion in
      the peptide in solution is strongly correlated with the residues downstream the
      peptide sequence, which may in part be attributed to long-range order imposed by
      the disulfide bond. The dynamics of the bound peptide are very different: the
      presence of two correlation times indicates that the Trp187 of the peptide has a
      fast motion (taur1 = 140 ps and r(0)1 = 0.14) relative to the overall rotation of
      the complex (taur2 = 3.4 ns and r(0)2 = 0.04). The correlation of the Trp residue
      with its neighboring amino acid residues and with the overall motion of the
      peptide is lost, giving rise to its rapid restricted motion. Thus, the internal
      dynamics of interacting peptides change on binding.

PMID- 12785054
TI  - Singlet excited-state lifetimes of cytosine derivatives measured by femtosecond
      transient absorption.
AB  - Lifetimes of the lowest excited singlet (S1) electronic states of various
      derivatives of the pyrimidine nucleobase cytosine (Cyt) were measured by the
      femtosecond transient absorption technique. The bases were excited in room
      temperature aqueous solution at 265 nm using approximately 200 fs pump pulses
      from a titanium-sapphire laser system. The decay of excited-state absorption
      (ESA) at visible probe wavelengths was used to determine the S1 lifetimes of a
      variety of modified Cyt compounds at different pH values by global fitting.
      Identical lifetimes were observed for Cyt and cytidine (Cyd) within experimental
      uncertainty, but ESA by the ribonucleoside was considerably stronger, suggesting
      that the ribose group increases the oscillator strength of the S1 --> SN
      transition. The S1 lifetime of the important minor base 5-methylcytosine (m5Cyt)
      is 7.2 +/- 0.4 ps at pH 6.8. The same lifetime was measured for the
      ribonucleoside 5-methylcytidine, but sugar substitution again increased the
      strength of the ESA signal. Protonation of Cyd and m5Cyt at low pH led to a
      modest decrease in their S1 lifetimes. On the other hand, deprotonation of Cyt
      and m5Cyt significantly increased the lifetime of their respective S1 states.
      These trends support the intermediacy of the n,pi* state localized on the
      carbonyl oxygen in the nonradiative decay mechanism of Cyt. Longer S1 lifetimes
      were observed for 5-fluorocytosine and N4-acetylcytosine. Collectively, these
      results illustrate the great potential of femtosecond laser spectroscopy for
      investigating excited-state dynamics in DNA and DNA components.

PMID- 12785055
TI  - Singlet oxygen-mediated hydroxyl radical production in the presence of phenols:
      whether DMPO-*OH formation really indicates production of *OH?
AB  - The reaction of singlet oxygen (1O2) generated by ultraviolet-A (UVA)-visible
      light (lambda > 330 nm) irradiation of air-saturated solutions of hematoporphyrin
      with phenolic compounds in the presence of a spin trap, 5,5-dimethyl-1-pyrroline
      N-oxide (DMPO), gave an electron spin resonance (ESR) spectrum characteristic of
      the DMPO-hydroxyl radical spin adduct (DMPO-*OH). In contrast, the ESR signal of
      5,5-dimethyl-2-pyrrolidone-N-oxyl, an oxidative product of DMPO, was observed in
      the absence of phenolic compounds. The ESR signal of DMPO-*OH decreased in the
      presence of either a *OH scavenger or a quencher of *O2 and under anaerobic
      conditions, whereas it increased depending on the concentration of DMPO. These
      results indicate both 1O2- and DMPO-mediated formation of free *OH during the
      reaction. When DMPO was replaced with 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline
      N-oxide (DEPMPO), no DEPMPO adduct of oxygen radical species was obtained. This
      suggests that 1O2, as an oxidizing agent, reacts little with DEPMPO, in which a
      strong electron-withdrawing phosphoryl group increases the oxidation potential of
      DEPMPO compared with DMPO. A linear correlation between the amounts of DMPO-*OH
      generated and the oxidation potentials of phenolic compounds was observed,
      suggesting that the electron-donating properties of phenolic compounds contribute
      to the appearance of *OH. These observations indicate that 1O2 reacts first with
      DMPO, and the resulting DMPO-1O2 intermediate is immediately decomposed/reduced
      to give *OH. Phenolic compounds would participate in this reaction as electron
      donors but would not contribute to the direct conversion of 1O2 to *OH.
      Furthermore, DEPMPO did not cause the spin-trapping agent-mediated generation of
      *OH like DMPO did.

PMID- 12785056
TI  - Photoreduction of 9,10-anthraquinone derivatives: transient spectroscopy and
      effects of alcohols and amines on reactivity in solution.
AB  - The photoreduction of 9,10-anthraquinone (AQ), the 2-methyl, 2-ethyl, 2,3
      dimethyl, 1,4-difluoro, 1-chloro and 1,8-dichloro derivatives as well as
      1,4,4a,9a-tetrahydroanthraquinone, 1,2-benzanthraquinone and 6,13
      pentacenequinone in nonaqueous solution at room temperature was studied by time
      resolved UV-visible spectroscopy. Upon 308 nm excitation of AQ the triplet state
      reacts with alcohols and triethylamine (TEA). The rate constant of triplet
      quenching by amines is close to the diffusion-controlled limit. The semiquinone
      radical *QH/ Q*- is the main intermediate, and the half-life of the second-order
      decay kinetics depends significantly on the donor and the medium. Photoinduced
      charge separation after electron transfer from amines to the triplet state of AQ
      in acetonitrile and the subsequent charge recombination or neutralization also
      were measured by transient conductivity. The maximum quantum yield, lambdairr =
      254 nm, of photoconversion into the strongly fluorescing 9,10
      dihydroxyanthracenes is close to unity. The fluorescence with maximum at 460-480
      nm and a lifetime of 20-30 ns disappears as a result of a complete recovery into
      AQ, when the dihydroxyanthracenes are exposed to oxygen. The mechanisms of
      photoreduction of parent AQ in acetonitrile by 2-propanol and in benzene and
      acetonitrile by TEA are discussed. The effects of AQ follow essentially the same
      pattern. The various functions of oxygen, e.g. (1) quenching of the triplet
      state; (2) quenching of the semiquinone radical, thereby forming HO2*/O2*-
      radicals; and (3) trapping of the dihydroxyanthracenes are outlined.

PMID- 12785057
TI  - Photostabilization of an entomopathogenic fungus using composite clay matrices.
AB  - To provide photostabilization for entomopathogenic fungi by anionic dyes,
      composite matrices based on clay-biopolymer combinations were prepared. In the
      first step, the negative surface charge of various clays (montmorillonite,
      attapulgite, bentonite and kaolinite) was reversed to positive by adsorption to
      the polycationic biopolymer chitosan. The second step involved adsorption of the
      toxicologically safe anionic dyes fast green (FG) and naphthol yellow S (NYS) to
      the clay complexes. Compared with cytotoxic photoprotectants like berberine,
      palmatine and acriflavine, the anionic dyes have no adverse effects up to a
      concentration of 1 M. In assays using various clay-chitosan-dye matrices and UV
      irradiation from a lamp source, it was evident that both FG and NYS provided
      considerable photostabilization for conidia of the entomopathogenic fungus
      Aschersonia spp. that served as a model biocontrol agent. Apparently, because of
      the light-dispersing property, bentonite and attapulgite per se provided
      significant photoprotection. All clay matrices containing FG provided a
      substantial photostabilization effect.

PMID- 12785058
TI  - Photodynamic effects of antioxidant substituted porphyrin photosensitizers on
      gram-positive and -negative bacterial.
AB  - Photodynamic treatment of the gram-negative bacteria Escherichia coli B and
      Acinetobacter baumannii and the gram-positive bacterium Staphylococcus aureus was
      performed using two newly devised and synthesized antioxidant carrier
      photosensitizers (antioxidant carrier sensitizers-2 [ACS-2] and antioxidant
      carrier sensitizers-3 [ACS-3]), which are butyl hydroxy toluene and propyl
      gallate substituted haematoporphyrins, respectively. It was found that ACS-2 is
      less reactive than other photosensitizers previously used for the same purpose,
      whereas ACS-3 is very effective against the multidrug-resistant bacterium A.
      baumannii, causing its complete eradication at a low fluence (approximately 7.5
      J/cm2) of blue light (407-420 nm) and a low concentration (10 microM). At a
      higher fluence (approximately 37.5 J/cm2) complete eradication of E. coli B can
      be obtained under the same conditions. Furthermore, X-ray microanalysis and
      ultrastructural changes indicate that ACS-3, especially in the case of
      photodynamic treatment of A. baumannii, interferes with membrane functions and
      causes the inactivation of the bacterium. ACS-3 may be suggested as a specific
      photosensitization agent for photoinactivation of gram-negative bacteria.

PMID- 12785059
TI  - Secondary reactive oxygen species extend the range of photosensitization effects
      in cells: DNA damage produced via initial membrane photosensitization.
AB  - The type-II photosensitization process is mediated by the formation of singlet
      oxygen (O2[1deltag]). The short lifetime of this species dictates that chemical
      reactions with biological substrates can only occur when O2(1deltag) is in very
      close proximity to the photosensitizer itself. In this study, deuteroporphyrin, a
      type-II, membrane-localized photosensitizer, was used to generate O2(1deltag) in
      human lymphoblast WTK-1 cells, and the range of influence was determined by a
      variety of biological assays. Surprisingly, the initial membrane-confined events
      were shown, by comet assay, to induce DNA damage in these cells. DNA damage was
      inhibited both by membrane-localized (alpha-tocopherol acetate) and by
      cytoplasmic (trolox) free radical scavengers. Comet formation also was inhibited
      by treatment at low temperature. DNA fragmentation was not influenced by
      treatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone, showing that apoptosis was not responsible for fragmentation.
      Taken together, these results show that primary photosensitization reactions
      involving O2(1deltag), even when tightly confined in extranuclear locations,
      leads to the production of secondary reactive oxygen species, probably as a
      result of lipid peroxidation, that can act at greater distances from the
      photosensitizer itself. These experiments were carried out under conditions where
      cell survival was significant and raise questions regarding DNA damage and
      mutagenesis pathways, even when extranuclear O2(1deltag)-generating compounds are
      used.

PMID- 12785060
TI  - Effect of preillumination on photomotile responses of the marine ciliate Fabrea
      salina.
AB  - Fabrea salina is a marine ciliate that shows photomotile responses such as
      positive phototaxis and a step-down photophobic reaction. We found that
      preilluminated F. salina cells show a phototactic response significantly greater
      than that of dark-adapted cells when exposed to the same phototactic light
      stimulus. In particular, positive phototaxis is strongly enhanced by
      preillumination. This enhancement effect depends on the preillumination light
      irradiance, on the total preillumination dose, and on the duration of the dark
      interval between preillumination and the phototaxis measurement. Our results show
      that the determining factor is the total preillumination dose given to the
      sample. The enhancement effect shows an asymptotic behavior over a certain range
      of energy values (10-200 W/m2). Further, the effect is transient; after 120 s in
      the dark, the cells lose any memory of the preillumination, independent of the
      preillumination energy received. These results are tentatively discussed in terms
      of light-driven membrane potential or membrane channel conductances.

PMID- 12785061
TI  - The effect of photoperiod and light irradiance on the antioxidant circadian
      system of two species of crayfish from different latitudes: Procambarus clarkii
      and P. digueti.
AB  - This work was carried out to study the antioxidant circadian system of two
      species of crayfish of different latitude origin. We investigated (1) whether
      both species possess glutathione circadian rhythms and (2) whether both species'
      rhythms differ in their ability to synchronize to 24 h cycles. Two batches of
      Procambarus clarkii and P. digueti were kept in (1) light-dark (LD) 12:12 low
      irradiance (LI) cycles and then exposed to (2) 72 h of complete darkness, (3) LD
      12:12 high irradiance (HI), (4) LD 20:4 LI and (5) LD 20:4 HI for 2 weeks. The
      midgut and hemolymph were sampled and reduced and oxidized glutathione as well as
      glutathione reductase and glutathione peroxidase were assayed. Cosinor and
      analysis of variance revealed differences between both species. Procambarus
      clarkii robust antioxidant circadian rhythms are able to entrain to all
      conditions resetting to lights on or off. However, the P. digueti weak circadian
      glutathione system did not entrain to the LD cycles, showing a random
      distribution of phases. In this species, LD 12:12 and 20:4 HI evidenced
      significant daily rhythms indicating a damped circadian antioxidative system that
      is enhanced by the effect of light. This suggests that each species'
      photoperiodic history determines the adaptive abilities of the circadian
      antioxidative mechanisms.

PMID- 12785062
TI  - The cascade mechanisms of nitric oxide as a second messenger of ultraviolet B in
      inhibiting mesocotyl elongations.
AB  - In this report, a number of physiological aspects was examined during
      developmental growth of maize seedling's mesocotyl. It was found that ultraviolet
      B (UVB) radiation was able to significantly induce nitric oxide synthase (NOS)
      activities and speedup the release of apparent nitric oxide (NO) of mesocotyl and
      that exogenous NO donor's rhizospheric treatments may mimic the responses of the
      mesocotyl to UVB radiation, such as the inhibition of mesocotyl elongation, the
      decrease in exo- and endoglucanase activities and the increase in protein content
      of cell wall of mesocotyl. When the seedlings were treated with N-nitro-L
      arginine, an inhibitor of NOS, the mesocotyl elongation was promoted, the exo-
      and endoglucanase activities were raised and the protein content was reduced.
      However, under UVB radiation, the effects of exogenous NO on several
      physiological aspects of mesocotyl were similar to those of exogenous reactive
      oxygen species (ROS) eliminator, N-acetyl-cysteine. All the physiological changes
      were associated with either the exogenous NO supply or the activities of NOS in
      plant. Accordingly, it is assumed that reduction in mesocotyl length caused by
      UVB radiation was possibly achieved through modification of the chemical
      properties of the cell wall polysaccharides, which was induced by NO and ROS
      synergically mediated changes in exo- and endo-beta-D-glucanases activities in
      cell walls, and NO was one of the main signaling molecule of UVB radiation in
      inhibiting mesocotyl elongations. So NO might function as both a second messenger
      and an antioxidant of UVB radiation during developmental growth of the mesocotyl.

PMID- 12785063
TI  - Identification of Arabidopsis genes regulated by high light-stress using cDNA
      microarray.
AB  - In plants, excess light has the potential to damage the photosynthetic apparatus.
      The damage is caused in part by reactive oxygen species (ROS) generated by
      electrons leaking from the photosynthetic electron transport system. To
      investigate the mechanisms equipped in higher plants to reduce high light (HL)
      stress, we surveyed the response of 7000 Arabidopsis genes to HL, taking
      advantage of the recently developed microarray technology. Our analysis revealed
      that 110 genes had a positive response to a 3 h treatment at a light intensity of
      150 W m(-2). In addition to the scavenging enzymes of ROS, the genes involved in
      biosynthesis of lignins and flavonoids are activated by HL and actually resulted
      in increased accumulation of lignins and anthocyanins. Comparing the HL
      responsive genes with drought-inducible genes identified with the same microarray
      system revealed a dense overlap between HL- and drought-inducible genes. In
      addition, we have identified 10 genes that showed upregulation by HL, drought,
      cold and also salt stress. These genes include RD29A, ERD7, ERD10, KIN1, LEA14
      and COR15a, most of which are thought to be involved in the protection of
      cellular components.

PMID- 12785064
TI  - Task switching mediates the attentional blink even without backward masking.
AB  - When two targets are presented in rapid succession, perception of the second
      target is impaired at short intertarget lags (100-700 msec). This attentional
      blink (AB) is thought to occur only when the second target is backward masked. To
      the contrary, we show that task switching between the targets can produce an AB
      even without masking (Experiments 1 and 3). Further, we show that task switching
      produces an AB only when the second target does not belong to a class of
      overlearned stimuli such as letters or digits (Experiments 1 and 4). When the
      second target is masked, however, an AB is invariably obtained regardless of
      switching or overlearning. We propose that task switching involves a time
      consuming process of reconfiguration of the visual system, during which the
      representation of the second target decays beyond recognition, resulting in an AB
      deficit. We suggest that overlearned stimuli are encoded in a form that, while
      maskable, decays relatively slowly, thus outlasting the delay due to
      reconfiguration and avoiding the AB deficit.

PMID- 12785065
TI  - Negative facial expression captures attention and disrupts performance.
AB  - In two experiments, participants counted features of schematic faces with
      positive, negative, or neutral emotional expressions. In Experiment 1 it was
      found that counting features took longer when they were embedded in negative as
      opposed to positive faces. Experiment 2 replicated the results of Experiment 1
      and also demonstrated that more time was required to count features of negative
      relative to neutral faces. However, in both experiments, when the faces were
      inverted to reduce holistic face perception, no differences between neutral,
      positive, and negative faces were observed, even though the feature information
      in the inverted faces was the same as in the upright faces. We suggest that,
      relative to neutral and positive faces, negative faces are particularly effective
      at capturing attention to the global face level and thereby make it difficult to
      count the local features of faces.

PMID- 12785067
TI  - Translation and competition among internal representations in a reverse Stroop
      effect.
AB  - In two experiments, the contributions of internal and external competition in a
      task known to produce a reverse Stroop effect were investigated. In this
      paradigm, the verbal meaning of an incongruent Stroop stimulus is identified by
      pointing to a patch of matching color--a task made difficult by the incongruent
      print color. The experiments showed that there was somewhat more interference
      when the (irrelevant) color in which the target word was printed was available as
      an alternate response patch than when it was not. However, significantly more
      interference was determined by whether the (irrelevant) print color belonged to
      the set of colors actually used as target words in the course of the experiment.
      Moreover, the same patterns of interference emerged when the task was altered so
      that the mere presence of the correct color had to be indicated with a keypress,
      rather than by pointing to the color's location. Consistent with translation
      models of Stroop interference, these results demonstrate the theoretical
      importance of competition among internal representations, rather than among
      stimuli or responses.

PMID- 12785066
TI  - Developmental change in the cross-modal Stroop effect.
AB  - E. M. Elliott, Cowan, and Valle-Inclan (1998) reported a cross-modal Stroop-like
      interference effect in adults when an auditory distractor (a color or noncolor
      word) occurred simultaneously with a color patch to be named. Response times were
      slower with color as opposed to noncolor distractors. To distinguish two accounts
      of this phenomenon, we tested 4- to 11-year-olds and adults. The suppression
      hypothesis posits that the irrelevant word enters a phonological buffer and is
      injurious to color naming if the participant is unable to suppress its
      representation in time. The concurrent processing hypothesis states that
      interference occurs when the distractor and the color name are lexically accessed
      at the same time. Our finding that the cross-modal Stroop effect occurred in
      young children even with a distractor presented 500 msec in advance of the color
      patch favors the suppression account. Development in executive functioning may
      also contribute to the interference effect's becoming progressively weaker with
      age.

PMID- 12785068
TI  - Inhibition of return and manual pointing movements.
AB  - To examine whether the motor inhibition of return (IOR) postulated by Taylor and
      Klein (1998, 2000) generalizes to manual guided movements or is restricted to
      saccadic responses, the following three experiments were conducted. The first
      experiment combined peripheral cues (which generate IOR) with four types of
      manual responses made to central targets (central arrow indicating the response
      location). The responses were made on a touch-screen and were the equivalent of
      either a detection keypress, a choice keypress, a detection-guided pointing
      movement, or a choice-guided pointing movement. No IOR was found for any of the
      responses. The second experiment replicated the main result under eye fixation
      control. In Experiment 3, peripheral cues and peripheral targets were used, and
      IOR was present in all responses. Overall, these finding suggest that motor-based
      IOR is restricted to the oculomotor system. Implications for motor-based IOR and
      attention-based IOR are discussed.

PMID- 12785069
TI  - Inhibition of return for objects and locations in static displays.
AB  - When orienting attention, inhibition mechanisms prevent the return of attention
      to previously examined stimuli. This inhibition of the return of attention (IOR)
      has been shown to be associated additively with location- and object-based
      representations. That is, when static objects are attended, IOR is associated
      with both the object and the location cued, and hence IOR is larger than when
      only spatial location is attended. Recently McAuliffe, Pratt, and O'Donnell
      (2001) failed to observe such additive effects except under a narrow set of
      conditions (at short cue-target intervals and using mixed blocks in which object-
      and pure location-based effects were probed in the same display). The present
      study shows that additive IOR effects are observed under conditions that violate
      all of these boundary conditions. The results also show that IOR is modulated by
      internal structural properties of objects. These findings are cosistent with the
      hypothesis that IOR operates over functionally independent object- and location
      based frames of reference.

PMID- 12785070
TI  - One factor underlies individual differences in auditory informational masking
      within and across age groups.
AB  - Masked threshold for a pure-tone signal can be substantially elevated whenever
      the listener is uncertain about the spectral or temporal properties of the
      masker, an effect referred to as auditory informational masking. Individual
      differences in the effect are large, with young children being most susceptible.
      When masker uncertainty is introduced by randomizing the frequencies of a
      multitone masker on each presentation, the function relating a child's pure-tone
      signal threshold to the number of masker components is found to be substantially
      elevated above that of most adults. The age effect and the individual differences
      among adults are not well understood, though a difference in the shapes of the
      masking functions suggests that different detection strategies may be involved.
      The present study reports results from a principal components analysis of
      informational masking functions obtained from 38 normal-hearing children ranging
      in age from 4 to 16 years and 46 normal-hearing adults ranging in age from 19 to
      38 years. The premise underlying the analysis is that if different detection
      strategies are involved, they should add independent sources of variance to the
      masking functions. Hence, more than one principal component (PC) should be
      required to account for a substantial proportion of the variance in these
      functions. The results, instead, supported the operation of a single underlying
      strategy with all but 17% of the variance accounted for by the first PC within
      and across age groups. An analysis of variance on the first two PCs showed that
      only the first changed with age, and a cluster analysis of the masking functions
      showed complete separation of clusters along this PC for all but 1 listener. The
      results are taken to suggest that large individual differences informational
      masking at all ages reflect differences in the extent to which masker uncertainty
      adds variance to the decision variable of an otherwise optimal decision strategy.

PMID- 12785071
TI  - Effect of grammatical gender on visual word recognition: evidence from lexical
      decision and eye movement experiments.
AB  - Lexical decision times and eye movements were recorded to determine whether
      grammatical gender can influence the visual recognition of isolated French nouns.
      This issue was investigated by assessing the use of two types of regularities
      between a noun's form and its gender--namely ending-to-gender regularities (e.g.,
      the final letter sequence -at appears only in masculine nouns and, thus, is
      predictive of masculine gender) and gender-to-ending regularities (e.g., feminine
      gender would predict the final letter e, whereas masculine gender would not).
      Previous studies have shown that noun endings are used by readers when they have
      to identify gender. However, the influence of ending-to-gender predictiveness has
      never been investigated in a lexical decision task, and the effect of gender-to
      ending regularities has never been evaluated at all. The results suggest that
      gender information can influence both the activation stage (Experiments 1 and 3)
      and the selection stage (Experiments 2 and 3) of the word recognition process.

PMID- 12785072
TI  - Countermanding saccades: evidence against independent processing of go and stop
      signals.
AB  - In a stop signal paradigm, subjects were instructed to make a saccade to a visual
      target appearing left or right of the fixation point. In 25% of the trials, an
      auditory stop signal was presented after a variable delay that required the
      subject to inhibit the saccade. Observed saccadic response times in stop failure
      trials were longer than predicted by Logan and Cowan's (1984) race model.
      Saccadic response time and amplitude decreased with the time between stop signal
      presentation and saccade execution, suggesting an inhibitory effect between the
      stop signal and the go signal processes that is not compatible with an
      independent race assumption. Moreover, countermanding a saccade was more
      difficult when stop and go signals appeared at the same location.

PMID- 12785073
TI  - The dynamical foundations of motion pattern formation: stability, selective
      adaptation, and perceptual continuity.
AB  - A dynamical model is used to show that global motion pattern formation for
      several different apparent motion stimuli can be embodied in the stable
      distribution of activation over a population of concurrently activated,
      directionally selective motion detectors. The model, which is based on motion
      detectors being interactive, noisy, and self-stabilizing, accounts for such
      phenomena as bistability, spontaneous switching, hysteresis, and selective
      adaptation. Simulations show that dynamical solutions to the motion
      correspondence problem for a bistable stimulus (two qualitatively different
      patterns are formed) apply as well to the solution for a monostable stimulus
      (only one pattern is formed) and highlight the role of interactions among
      sequentially stimulated detectors in establishing the state dependence and,
      thereby, the temporal persistence of percepts.

PMID- 12785074
TI  - The role of representational volatility in recognizing pre- and postchange
      objects.
AB  - Theories relating attention to change blindness (CB) imply that representations
      of objects in the focus of attention are stable and coherent. However, CB occurs
      for objects in the focus of attention. Here, we explore this apparent
      contradiction and the possibility that changes can be detected without having a
      complete and stable representation of the prechange object. The first experiment
      required observers to recognize a prechange object and a postchange object after
      viewing arrays of various sizes in which the prechange object was replaced by the
      postchange object after a brief delay. Results indicated that the representation
      of the prechange object was strong enough to cue a change but not strong enough
      to support accurate recognition. The remaining experiments demonstrated that the
      representation of the prechange object is volatile in that a shift in the display
      or the presence of a postchange object can disrupt the representation. These
      findings add to current theories of attention and representations by showing that
      attention may result in volatile representations that can support change
      detection without supporting accurate recognition.

PMID- 12785075
TI  - Orientation invariance in visual object priming depends on prime-target
      asynchrony.
AB  - Two experiments are reported in which orientation effects on visual object
      recognition latency were examined. In Experiment 1, we assessed picture-naming
      performance as a function of image-plane stimulus orientation and found
      increasing response times with increased misorientation of the stimulus. In
      Experiment 2, we examined the repetition priming effect on the identification of
      upright targets as a function of prime orientation. With time delays of 100, 200,
      or 500 msec between the onset of the prime and that of the target (i.e., stimulus
      onset asynchrony [SOA]), the magnitude of the priming effect decreased with
      increasing misorientation of the prime. These results contrast with the
      orientation-invariant priming effects reported in some previous repetition
      priming studies. These investigations all used relatively long prime-target SOAs.
      Confirming the crucial role of the latter variable, Experiment 2 shows that the
      magnitude of the repetition priming effect is invariant across prime orientations
      with an SOA of 1,000 msec. The possible implications of the present observations
      with respect to the issue of orientation invariance versus dependency of the
      visual object recognition processare discussed.

PMID- 12785076
TI  - A test of the optimal classifier's independence assumption in perceptual
      categorization.
AB  - Observers completed perceptual categorization tasks that included separate base
      rate/payoff manipulations, corresponding simultaneous base-rate/payoff
      manipulations, and conflicting simultaneous base-rate/payoff manipulations.
      Performance (1) was closer to optimal for 2:1 than for 3:1 base-rate/payoff
      ratios and when base rates as opposed to payoffs were manipulated, and (2) was
      more in line with the predictions from the flat-maxima hypothesis than from the
      independence assumption of the optimal classifier in corresponding and
      conflicting simultaneous base-rate/payoff conditions. A hybrid model that
      instantiated simultaneously the flat-maxima and the competition between reward
      and accuracy maximization (COBRA) hypotheses was applied to the data. The hybrid
      model was superior to a model that incorporated the independence assumption,
      suggesting that violations of the independence assumption are to be expected and
      are well captured by the flat-maxima hypothesis without requiring any additional
      assumptions. The parameters indicated that observers' reward-maximizing decision
      criterion rapidly approaches the optimal value and that more weight is placed on
      accuracy maximization in separate and corresponding simultaneous base-rate/payoff
      conditions than in conflicting simultaneous base-rate/payoff conditions.

PMID- 12785077
TI  - 'DNR' policies must not be just paper exercises.

PMID- 12785078
TI  - Does NHS Direct deserve its recent criticism?

PMID- 12785080
TI  - Case 33: patient abuse. Administration of enema without warning or explanation.

PMID- 12785083
TI  - The use of holistic assessment in the treatment of leg ulcers.
AB  - Leg ulcers are costly to both patients and also the NHS. It is therefore of
      paramount importance that the treatment regimen is based on a holistic assessment
      to determine the underlying aetiology. It is only then that an appropriate
      treatment plan can be formulated. This article reviews the issues involved in the
      holistic assessment of leg ulcers.

PMID- 12785084
TI  - Observation and documentation of bedside blood transfusion.
AB  - Correct administration of blood and the management of the transfused patient are
      a fundamental element of transfusion safety. Recently published guidelines from
      the British Committee for Standards in Haematology highlight that most serious
      transfusion complications occur within the first 15 minutes. They recommend
      baseline observations before and 15 minutes after commencement of each unit of
      blood. Using a Royal College of Physicians (RCP) proforma, 100 clinical case
      notes were examined retrospectively for standards of transfusion documentation
      and bedside observation. The audit identified that bedside practice was variable
      and that only 16% of cases met this standard. Most wards continued with hourly
      observations in uncomplicated cases. Trust guidelines and a staff education
      programme have been implemented to address the audit results.

PMID- 12785085
TI  - Critical incident: reflection on the process of terminal weaning.
AB  - The article uses critical incident analysis to reflect on the process of terminal
      weaning. Terminal weaning is defined in the context of withdrawing ventilatory
      support when the expected outcome is the patient's death. Basic ethical concepts
      are identified, and the role of the nurse in ethical decision making is discussed
      in relation to the associated professional and legal issues. Conflict exists
      between professional and legal accountability in relation to advocacy. Caution is
      advised with regard to nurses becoming involved in the decision to terminally
      wean, and its practice.

PMID- 12785086
TI  - Enhancing clinical effectiveness among clinical nurse specialists.
AB  - This article describes the findings of an exploratory study which aimed to
      discover how clinically effective nursing care is fostered among clinical nurse
      specialists (CNSs) and nurse practitioners (NPs) in an NHS trust in East London. 
      The study was funded by the Central and East London Education Consortium in
      January 1999.  Qualitative approaches included non-participant observation of
      practice, interviews during observaton and focus group meetings,  Findings from
      the research identify areas that both foster and hinder the ability of the CNSs
      and NPs to engage in and provide clinically effective nursing care.

PMID- 12785087
TI  - A staff support mechanism: the transformational partnership.
AB  - There have been many changes in nursing over the past decade, e.g. the movement
      of nursing education into higher educational sectors and the generation of many
      new nursing roles. The development of senior roles within nursing could
      potentially lead to isolation and, consequently, there may be calls for
      complementary support mechanisms. A transformational partnership is advocated,
      whereby nurses working in different organizations/specialties can provide mutual
      support. Existing support mechanisms for senior nursing can be variable and a
      transformational partnership can complement these as well as providing mutual
      clinical support. There are many advantages to this form of partnership which
      include professional and personal development as well as time out to reflect on
      practice. It requires commitment to the validity of the concept of professional
      support across traditional boundaries. A framework based on Holt's (1994) change
      theory is suggested as a method of implementing this initiative more widely
      within neighbouring organizations.

PMID- 12785088
TI  - Respite care innovations for carers of people with dementia.
AB  - The importance of family carers to making a reality of community care policy is
      now widely recognized. The central role of carers was recently confirmed by the
      launch of 'The Carers' National Strategy' (Department of Health (DoH), 1999). In
      his foreword to this document, the Prime Minister, Tony Blair, acknowledged
      carers as the 'unsung' heros of British life' and pledged to raise the level and
      quality of the support that carers receive. Although the primary responsibility
      for meeting carers' needs still rests with local authorities the strategy charges
      everyone involved in the caring services with paying greater attention to
      supporting family members. In allocating monies to move the strategy forward the
      Government identified the provision of short breaks as one of the major
      priorities. This article describes the development of an innovative service for
      people with dementia and their carers in Sheffield. The service evolved following
      a research study on the views of carers and of people with dementia which
      identified the need for the provision of short breaks which were flexible,
      responsive and person-centred.

PMID- 12785089
TI  - Intrasite Gel and Intrasite Conformable: the hydrogel range.
AB  - Wound management can be a confusing area of nursing practice. Even when an
      holistic patient assessment has been undertaken healthcare professionals
      frequently ask for guidance when faced with choosing the most appropriate wound
      management product. This article reviews two hydrogels from Smith & Nephew
      Healthcare--Intrasite Gel and Intrasite Conformable, which is the latest addition
      to the hydrogel range.

PMID- 12785090
TI  - An evaluation of the Parema four-layer bandage system.
AB  - This article gives an overview of the treatment and causes of venous leg ulcers
      and focuses on a new four-layer bandage system (K-Four from Parema) which can be
      used in the treatment of these ulcers. The article features preliminary
      observations of this new system, which was used on 10 patients who had previously
      worn multilayer compression.

PMID- 12785091
TI  - Mechanics and imaging of single DNA molecules.
AB  - We review recent experiments that have revealed mechanical properties of single
      DNA molecules using advanced manipulation and force sensing techniques(scanning
      force microscopy (SFM), optical or magnetic tweezers, microneedles). From such
      measurements, intrinsic relevant parameters (persistence length, stretch modulus)
      as well as their dependence on external parameters (non-physiological conditions,
      coating with binding agents or proteins) are obtained on a single-molecule level.
      In addition, imaging of DNA molecules using SFM is presented.

PMID- 12785092
TI  - Stretching and imaging single DNA molecules and chromatin.
AB  - The advent of single-molecule biology has allowed unprecedented insight into the
      dynamic behavior of biological macromolecules and their complexes. Unexpected
      properties, masked by the asynchronous behavior of myriads of molecules in bulk
      experiments, can be revealed; equally importantly, individual members of a
      molecular population often exhibit distinct features in their properties.
      Finally, the single-molecule approaches allow us to study the behavior of
      biological macromolecules under applied tension or torsion: understanding the
      mechanical properties of these molecules helps us understand how they function in
      the cell. The aim of this chapter is to summarize and critically evaluate the
      properties of single DNA molecules and of single chromatin fibers. The use of the
      high-resolution imaging capabilities of the atomic force microscopy has been
      covered, together with manipulating techniques such as optical fibers, optical
      and magnetic tweezers, and flow fields. We have learned a lot about DNA and how
      it responds to applied forces. It is also clear that even though the study of the
      properties of individual chromatin fibers has just begun, the single-molecule
      approaches are expected to provide a wealth of information concerning the
      mechanical properties of chromatin and the way its structure changes during
      processes like transcription and replication.

PMID- 12785093
TI  - Optical tweezers stretching of chromatin.
AB  - Recently significant success has emerged from exciting research involving
      chromatin stretching using optical tweezers. These experiments, in which a single
      chromatin fibre is attached by one end to a micron-sized bead held in an optical
      trap and to a solid surface or second bead via the other end, allows manipulation
      and force detection at a single-molecule level. Through force-induced stretching
      of chromatin, mechanical properties, specific intermolecular bond strengths and
      DNA-protein association and dissociation kinetics have been determined. These
      studies will be extremely fruitful in terms of understanding the function of
      chromatin structure and its dynamics within the cell.

PMID- 12785095
TI  - Varieties of elastic protein in invertebrate muscles.
AB  - Elastic proteins in the muscles of a nematode (Caenorhabditis elegans), three
      insects (Drosophila melanogaster, Anopheles gambiae, Bombyx mori) and a
      crustacean (Procambus clarkii) were compared. The sequences of thick filament
      proteins, twitchin in the worm and projectin in the insects, have repeating
      modules with fibronectin-like (Fn) and immunoglobulin-like (Ig) domains conserved
      between species. Projectin has additional tandem Igs and an elastic PEVK domain
      near the N-terminus. All the species have a second elastic protein we have called
      SLS protein after the Drosophila gene, sallimus. SLS protein is in the I-band.
      The N-terminal region has the sequence of kettin which is a spliced product of
      the gene composed of Ig-linker modules binding to actin. Downstream of kettin,
      SLS protein has two PEVK domains, unique sequence, tandem Igs, and Fn domains at
      the end. PEVK domains have repeating sequences: some are long and highly
      conserved and would have varying elasticity appropriate to different muscles.
      Insect indirect flight muscle (IFM) has short I-bands and electron micrographs of
      Lethocerus IFM show fine filaments branching from the end of thick filaments to
      join thin filaments before they enter the Z-disc. Projectin and kettin are in
      this region and the contribution of these to the high passive stiffness of
      Drosophila IFM myofibrils was measured from the force response to length
      oscillations. Kettin is attached both to actin near the Z-disc and to the end of
      thick filaments, and extraction of actin or digestion of kettin leads to rapid
      decrease in stiffness; residual tension is attributable to projectin. The
      wormlike chain model for polymer elasticity fitted the force-extension curve of
      IFM myofibrils and the number of predicted Igs in the chain is consistent with
      the tandem Igs in Drosophila SLS protein. We conclude that passive tension is due
      to kettin and projectin, either separate or linked in series.

PMID- 12785094
TI  - Micromechanical studies of mitotic chromosomes.
AB  - We review micromechanical experiments on mitotic chromosomes. We focus on work
      where chromosomes were extracted from prometaphase amphibian cells, and then
      studied by micromanipulation and microfluidic biochemical techniques. These
      experiments reveal that chromosomes have well-behaved elastic response over a
      fivefold range of stretching, with an elastic modulus similar to that of a
      loosely tethered polymer network. Perturbation by microfluidic 'spraying' of
      various ions reveals that the mitotic chromosome can be rapidly and reversibly
      decondensed or overcondensed, i.e. that the native state is not maximally
      compacted. Finally, we discuss microspraying experiments of DNA-cutting enzymes
      which reveal that the element which gives mitotic chromosomes their mechanical
      integrity is DNA itself. These experiments indicate that chromatin-condensing
      proteins are not organized into a mechanically contiguous 'scaffold', but instead
      that the mitotic chromosome is best thought of as a cross-linked network of
      chromatin. Preliminary results from restriction-enzyme digestion experiments
      indicate a spacing between chromatin 'cross-links' of roughly 15 kb, a size
      similar to that inferred from classical chromatin-loop-isolation studies. We
      compare our results to similar experiments done by Houchmandzadeh and Dimitrov (J
      Cell Biol 145: 215-213 (1999)) on chromatids reconstituted using Xenopus egg
      extracts. Remarkably, while the stretching elastic response of the reconstituted
      chromosomes is similar to that observed for chromosomes from cells, the
      reconstituted chromosomes are far more easily bent. This result suggests that
      reconstituted chromatids have a large-scale structure which is quite different
      from chromosomes in somatic cells. More generally our results suggest a strategy
      for the use of micromanipulation methods for the study of chromosome structure.

PMID- 12785096
TI  - Single-molecule measurement of elasticity of serine-, glutamate- and lysine-rich
      repeats of invertebrate connectin reveals that its elasticity is caused
      entropically by random coil structure.
AB  - Invertebrate connectin (I-connectin) is a 1960 kDa elastic protein linking the Z
      line to the tip of the myosin filament in the giant sarcomere of crayfish claw
      closer muscle (Fukuzawa et al., 2001 EMBO J 20: 4826-4835). I-Connectin can be
      extended up to 3.5 microns upon stretch of giant sarcomeres. There are several
      extensible regions in I-connectin: two long PEVK regions, one unique sequence
      region and Ser-, Glu- and Lys-rich 68 residue-repeats called SEK repeats. In the
      present study, the force measurement of the single recombinant SEK polypeptide
      containing biotinylated BDTC and GST tags at the N and C termini, respectively,
      were performed by intermolecular force microscopy (IFM), a refined AFM system.
      The force vs. extension curves were well fit to the wormlike chain (WLC) model
      and the obtained persistence length of 0.37 +/- 0.01 nm (n = 11) indicates that
      the SEK region is a random coil along its full length. This is the first
      observation of an entropic elasticity of a fully random coil region that
      contributes to the physiological function of I-connectin.

PMID- 12785097
TI  - Titin as a modular spring: emerging mechanisms for elasticity control by titin in
      cardiac physiology and pathophysiology.
AB  - Titin is a giant elastic protein that functions as a molecular spring that
      develops passive muscle stiffness. Here we discuss the molecular basis of titin's
      extensibility, how titin's contribution to passive muscle stiffness may be
      adjusted and how adjustment of titin's stiffness may influence muscle
      contraction. We also focus on ligands that link titin to membrane channel
      activity, protein turnover and gene expression.

PMID- 12785098
TI  - Species variations in cDNA sequence and exon splicing patterns in the extensible
      I-band region of cardiac titin: relation to passive tension.
AB  - Titin is believed to play a major role in passive tension development in cardiac
      muscle. The cDNA sequence of cardiac titin in the I-band sarcomeric region was
      determined for several mammalian species. Contiguous sequences of 3749, 12,230,
      6602, and 11,850 base pairs have been obtained for the rat N2B, rat N2BA, dog
      N2B, and dog N2BA isoforms respectively. The length of the PEVK region of the N2B
      isoform did not correlate with rest tension properties since the only species
      showing an altered length was the dog that expressed a shorter form. No
      differences were found between the N2B PEVK lengths in ventricular and atrial
      muscle. New N2BA splicing pathways in the first tandem Ig region were found in
      human and dog cardiac muscle. Most of the rat and dog sequences were 85-95%
      identical with the reported human sequence. However, the N2B unique amino acid
      sequences of rat and dog were only 51 and 67% identical to human. The rat N2B
      unique sequence was 526 amino acids in length compared to 572 in human. The
      difference in length was due to deletion of amino acid segments from six
      different regions of the N2B unique domain. Patterns of PEVK exon expression were
      also much different in the dog, human, and rat. Six separate dog N2BA PEVK clones
      were sequenced, and all had different exon splice combinations yielding PEVK
      lengths ranging from 703 to 900 amino acids. In contrast a rat N2BA clone had a
      PEVK length of 525 amino acids, while a human clone had an 908 amino acid PEVK
      segment. Thus, in addition to the higher proportion of the shorter N2B isoform
      found in rat compared with dog cardiac muscle observed previously, shorter N2B
      unique and N2BA PEVK segments may also contribute to the greater passive tension
      in cardiac muscle from rats.

PMID- 12785099
TI  - Cardiac titin: molecular basis of elasticity and cellular contribution to elastic
      and viscous stiffness components in myocardium.
AB  - Myocardium resists the inflow of blood during diastole through stretch-dependent
      generation of passive tension. Earlier we proposed that this tension is mainly
      due to collagen stiffness at degrees of stretch corresponding to sarcomere
      lengths (SLS) > or = 2.2 microns, but at shorter lengths, is principally
      determined by the giant sarcomere protein titin. Myocardial passive force
      consists of stretch-velocity-sensitive (viscous/viscoelastic) and velocity
      insensitive (elastic) components; these force components are seen also in
      isolated cardiac myofibrils or skinned cells devoid of collagen. Here we examine
      the cellular/myofibrillar origins of passive force and describe the contribution
      of titin, or interactions involving titin, to individual passive-force
      components. We construct force-extension relationships for the four distinct
      elastic regions of cardiac titin, using results of in situ titin segment
      extension studies and force measurements on isolated cardiac myofibrils. Then, we
      compare these relationships with those calculated for each region with the
      wormlike-chain (WLC) model of entropic polymer elasticity. Parameters used in the
      WLC calculations were determined experimentally by single-molecule atomic force
      microscopy measurements on engineered titin domains. The WLC modelling faithfully
      predicts the steady-state-force vs. extension behavior of all cardiac-titin
      segments over much of the physiological SL range. Thus, the elastic-force
      component of cardiac myofibrils can be described in terms of the entropic-spring
      properties of titin segments. In contrast, entropic elasticity cannot account for
      the passive-force decay of cardiac myofibrils following quick stretch (stress
      relaxation). Instead, slower (viscoelastic) components of stress relaxation could
      be simulated by using a Monte-Carlo approach, in which unfolding of a few
      immunoglobulin domains per titin molecule explains the force decay. Fast
      components of stress relaxation (viscous drag) result mainly from interaction
      between actin and titin filaments; actin extraction of cardiac sarcomeres by
      gelsolin immediately suppressed the quickly decaying force transients. The
      combined results reveal the sources of velocity sensitive and insensitive force
      components of cardiomyofibrils stretched in diastole.

PMID- 12785100
TI  - Stretching and visualizing titin molecules: combining structure, dynamics and
      mechanics.
AB  - The details of the global and local structure and function of titin, a giant
      filamentous intrasarcomeric protein are largely undiscovered. Here we discuss a
      combination of bulk-solution and novel single-molecule techniques that may lend
      unique insights into titin's molecular dynamic, structural and mechanical
      characteristics.

PMID- 12785101
TI  - Unfolding of titin domains studied by molecular dynamics simulations.
AB  - Titin, a approximately 1 micron long protein found in striated muscle myofibrils,
      possesses unique elastic properties. The extensible behavior of titin has been
      demonstrated in atomic force microscopy and optical tweezer experiments to
      involve the reversible unfolding of individual immunoglobulin-like (Ig) domains.
      We have used steered molecular dynamics (SMD), a novel computer simulation
      method, to investigate the mechanical response of single titin Ig domains upon
      stress. Simulations of stretching Ig domains I1 and I27 have been performed in a
      solvent of explicit water molecules. The SMD approach provides a detailed
      structural and dynamic description of how Ig domains react to external forces.
      Validation of SMD results includes both qualitative and quantitative agreement
      with AFM recordings. Furthermore, combining SMD with single molecule experimental
      data leads to a comprehensive understanding of Ig domains' mechanical properties.
      A set of backbone hydrogen bonds that link the domains' terminal beta-strands
      play a key role in the mechanical resistance to external forces. Slight
      differences in architecture permit a mechanical unfolding intermediate for I27,
      but not for I1. Refolding simulations of I27 demonstrate a locking mechanism.

PMID- 12785102
TI  - Mechanical response of single filamin A (ABP-280) molecules and its role in the
      actin cytoskeleton.
AB  - Filamin A produces isotropic cross-linked three-dimensional orthogonal networks
      with actin filaments in the cortex and at the leading edge of cells. Filamin A
      also links the actin cytoskeleton to the plasma membrane via its association with
      various kinds of membrane proteins. Recent new findings strongly support that
      filamin A plays important roles in the mechanical stability of plasma membrane
      and cortex, formation of cell shape, mechanical responses of cells, and cell
      locomotion. To elucidate the mechanical properties of the actin/filamin A network
      and the complex of membrane protein-filamin A-actin cytoskeleton, the mechanical
      properties of single human filamin A (hsFLNa) molecules in aqueous solution were
      investigated using atomic force microscopy. Ig-fold domains of filamin A can be
      unfolded by the critical external force (50-220 pN), and this unfolding is
      reversible, i.e., the refolding of the unfolded chain of the filamin A occurs
      when the external force is removed. Due to this reversible unfolding of Ig-fold
      domains, filamin A molecule can be stretched to several times the length of its
      native state. Based on this new feature of filamin A as the 'large-extensible
      linker', we describe our hypothesis for the mechanical role of filamin A in the
      actin cytoskeletons in cells and discuss its biological implications. In this
      review, function of filamin A in actin cytoskeleton, mechanical properties of
      single filamin A proteins, and the hypothesis for the mechanical role of filamin
      A in the actin cytoskeletons are discussed.

PMID- 12785103
TI  - Mechanics of vimentin intermediate filaments.
AB  - It is increasingly evident that the cytoskeleton of living cells plays important
      roles in mechanical and biological functions of the cells. Here we focus on the
      contribution of intermediate filaments (IFs) to the mechanical behaviors of
      living cells. Vimentin, a major structural component of IFs in many cell types,
      is shown to play an important role in vital mechanical and biological functions
      such as cell contractility, migration, stiffness, stiffening, and proliferation.

PMID- 12785104
TI  - Mechanics of elastin: molecular mechanism of biological elasticity and its
      relationship to contraction.
AB  - Description of the mechanics of elastin requires the understanding of two
      interlinked but distinct physical processes; the development of entropic elastic
      force and the occurrence of hydrophobic association. Elementary statistical
      mechanical analysis of AFM single-chain force-extension data of elastin model
      molecules identifies damping of internal chain dynamics on extension as a
      fundamental source of entropic elastic force and eliminates the requirement of
      random chain networks. For elastin and its models, this simple analysis is
      substantiated experimentally by the observation of mechanical resonances in the
      dielectric relaxation and acoustic absorption spectra, and theoretically by the
      dependence of entropy on frequency of torsion-angle oscillations, and by
      classical molecular-mechanics and dynamics calculations of relaxed and extended
      states of the beta-spiral description of the elastin repeat, (GVGVP)n. The role
      of hydrophobic hydration in the mechanics of elastin becomes apparent under
      conditions of isometric contraction. During force development at constant length,
      increase in entropic elastic force resulting from decrease in elastomer entropy
      occurs under conditions of increase in solvent entropy. This eliminates the
      solvent entropy change as the entropy change that gives rise to entropic elastic
      force and couples association of hydrophobic domains to the process. Therefore,
      association of hydrophobic domains within the elastomer at fixed length stretches
      interconnecting dynamic chain segments and causes an increase in the entropic
      elastic force due to the resulting damping of internal chain dynamics.
      Fundamental to the mechanics of elastin is the inverse temperature transition of
      hydrophobic association that occurs with development of mechanical resonances
      within fibrous elastin and polymers of repeat elastin sequences, which, with
      design of truly minimal changes in sequence, demonstrate energy conversions
      extant in biology and demonstrate the special capacity of bound phosphates to
      raise the free energy of hydrophobic association.

PMID- 12785105
TI  - Molecular basis for the extensibility of elastin.
AB  - Elastin is a cross-linked protein in the extracellular matrix that provides
      elasticity for many tissues. Its soluble precursor (tropoelastin) has two major
      types of alternating domains: (1) hydrophilic cross-linked domains rich in Lys
      and Ala and (2) hydrophobic domains (responsible for elasticity) rich in Val,
      Pro, and Gly, which often occur in repeats of VPGVG or VGGVG. Since native
      elastin is large and insoluble, many studies have focused on elastin-based
      peptides in an effort to elucidate its structure-function relationship. This
      review focuses on the molecular basis of elastin's conformational properties and
      associated elasticity. From both experimental and simulation approaches, elastin
      can be described as a two-phase model consisting of dynamic hydrophobic domains
      in water. The hydrophobic domain of elastin is best described as a compact
      amorphous structure with distorted beta-strands, fluctuating turns, buried
      hydrophobic residues, and main-chain polar atoms that from hydrogen bonds with
      water. Water plays a critical role in determining elastin's conformational
      behavior, making elastin extremely dynamic in its relaxed state and providing an
      important source of elasticity.

PMID- 12785106
TI  - Stretching fibronectin.
AB  - Fibronectin (FN) matrix fibrils assembled in cell culture have been observed to
      stretch in response to cell movements, and when broken relax to 1/3 to 1/4 of
      their rest length. Two molecular mechanisms have been proposed, for the
      elasticity. One proposes that FN molecules in relaxed fibers are bent and looped
      into a compact conformation, and stretching pulls the molecules into the extended
      conformation but domains remain folded. The second proposes that molecules in
      fibrils are already extended, and stretching is produced by force-induced
      unfolding of FN type III domains. Experimental observations that may help
      distinguish these two possibilities are discussed.

PMID- 12785108
TI  - Gulliver meets Descartes: early modern concepts of age-related memory loss.
AB  - Age-related memory loss was a marginal issue in medical discussions during early
      modern times and until well into the second half of the 17th century. There are
      many possible explanations: the lack of similar traditions in antiquity and in
      the Middle Ages, insufficient physiological and morphological knowledge of the
      brain, and the underlying conflict between idealistic and materialistic
      perspectives on the functions of the soul and the conditions of these in old age.
      After these boundaries had been pushed back by the influence of Cartesianism and
      Iatromechanism, the problem of age-related memory loss was increasingly regarded
      as a physical illness and began to receive more attention. This trend first
      occurred in medicine, before spreading to the literary world, where the novel
      "Gulliver's Travels" is one clear and famous example.

PMID- 12785107
TI  - Fibrillin-rich microfibrils: elastic biopolymers of the extracellular matrix.
AB  - Fibrillin-rich microfibrils are evolutionarily ancient macromolecular assemblies
      of the extracellular matrix. They have unique extensible properties that endow
      vascular and other tissues with long-range elasticity. Microfibril extensibility
      supports the low pressure closed circulations of lower organisms such as
      crustaceans. In higher vertebrates, microfibrils act as a template for elastin
      deposition and are components of mature elastic fibres. In man, the importance of
      microfibrils is highlighted by the linkage of mutations in their principal
      structural component, fibrillin-1, to the heritable disease Marfan syndrome which
      is characterised by severe cardiovascular, skeletal and ocular defects. When
      isolated from tissues, fibrillin-rich microfibrils have a complex ultrastructural
      organisation with a characteristic 'beads-on-a-strong' appearance. X-ray fibre
      diffraction studies and biomechanical testing have shown that microfibrils are
      reversibly extensible at tissue extensions of 100%. Ultrastructural analysis and
      3D reconstructions of isolated microfibrils using automated electron tomography
      have revealed new details of how fibrillin molecules are aligned within
      microfibrils in untensioned and extended states, and delineated the role of
      calcium in regulating microfibril beaded periodicity, rest length and molecular
      organisation. The molecular basis of how fibrillin molecules assemble into
      microfibrils, the central role of cells in regulating this process, and the
      identity of other molecules that may coassemble into microfibrils are now being
      elucidated. This information will enhance our understanding of the elastic
      mechanism of these unique extracellular matrix polymers, and may lead to new
      microfibril-based strategies for repairing elastic tissues in ageing and disease.

PMID- 12785109
TI  - Sigmund Freud's contribution to the history of the neuronal cytoskeleton.
AB  - In the summers of 1879 and 1881, while Freud was a research student in Ernst von
      Brucke's laboratory at the Institute of Physiology at the University of Vienna,
      he carried out an important though seldom remembered investigation on the
      internal structure of nerve fibers and cells. His contribution to this field is
      here examined in the context of the 19th-century debate regarding the existence
      of neurofibrils and of present views on the cytoskeleton. Freud was able to
      discern separate fine fibrils following straight courses within the nerve fibers,
      as well as concentric loops of striae surrounding the nuclei and converging
      towards the processes of the cell bodies in crayfish nervous tissue. He thus
      confirmed and extended observations made by Robert Remak almost 40 years earlier,
      which had remained controversial. Electron microscopy of the crustacean nervous
      system confirmed Freud's main points, which in turn vindicated those of Remak.
      Both researchers were looking at small bundles of microtubules, and thus they
      were among the first to picture the lacy intracellular framework that future cell
      biologists would call the cytoskeleton.

PMID- 12785110
TI  - Recollections of a part-time amateur neurohistorian.

PMID- 12785111
TI  - The James Ramsay Hunt case books.
AB  - James Ramsay Hunt (1874-1937) was one of the pioneers of early-twentieth-century
      American neurology. The James Ramsay Hunt Case Books, Columbia University, were
      created by Hunt and chronicle his experience with private patients from 1903
      until 1937. This resource is not widely known to scholars and the content of
      these 30 volumes has not been described in detail. The purpose of this report is
      to describe this resource in terms of its organization, general contents and
      special features. The books contain the clinical records of 5,019 consecutive
      patients. The largest proportion had neurasthenia or psychiatric diagnoses,
      followed by those with neuropathies, manifestations of neurosyphilis, migraine
      and epilepsy. The books, through the enclosed correspondence, photographs, and
      poetry sent by patients, reveal a close relationship between the patients and
      their physician. Hunt's drawings are a special feature of the early volumes,
      including his original unpublished drawing of the lesions associated with his
      herpetic geniculate ganglion syndrome. The Case Books, by providing an indexed
      and permanent record of cases, would have made it easier for Hunt to cross
      reference patients with similar clinical characteristics when he was in the
      process of describing a new syndrome. These Case Books provide a valuable
      perspective of the practice of neurology in early-twentieth-century America.

PMID- 12785112
TI  - Asbjorn Folling and the discovery of phenylketonuria.
AB  - In 1934, the Norwegian biochemist and physician Asbjorn Folling described an
      inherited metabolic disorder characterized by severe intellectual impairment,
      motor problems, and skin abnormalities. He found that affected individuals could
      be identified by the abnormal excretion of phenylpyruvic acid in their urine. The
      disorder, which Folling initially termed imbecillitas phenylpyrouvica, would
      later come to be known as phenylketonuria or PKU. The present paper focuses on
      the story of Folling's discovery and his subsequent contributions to the area of
      study. In the years that have followed, research on PKU has continued to play a
      major role in the neurosciences, shaping our understanding of genetic disorders,
      human metabolism, and brain development.

PMID- 12785113
TI  - An American pioneer neurosurgeon and medical historian.

PMID- 12785114
TI  - The correspondence between Bernard Brouwer and John Fulton (1930-1940).
AB  - In 1933, Bernard Brouwer (1881-1949), first professor of neurology in Amsterdam
      (1923), made his second lecture tour in the USA. He met John Fulton (1899-1960)
      who had recently assumed the position of Sterling professor of physiology (1930).
      Next to clinical neurology, Brouwer had become well-known by his clinical
      anatomical, experimental neuroanatomical, and comparative neuroanatomical work at
      the Central Institute for Brain Research in Amsterdam. At the time, John Fulton,
      pupil of Sherrington and Cushing, was particularly interested in research of the
      primate central nervous system. The correspondence between Brouwer and Fulton
      (1930-1940), preserved at the Manuscripts and Archives Division of Yale Library,
      provides an opportunity to study international exchange of neuroscientific
      knowledge in the first half of the 20th century. Brouwer and Fulton first met
      during the first International Congress of Neurology at Berne in 1931, where they
      discussed the anatomy of optic tracts. Next to this subject, the correspondence
      in that year dealt with the crossed and uncrossed pyramidal tracts. Brouwer's
      visit at Yale (1933) was well appreciated as appears from their correspondence as
      well as from Fulton's diary. Fulton sent several students to Amsterdam, including
      Margaret Kennard (1899-1976) who visited Amsterdam in order to "receive further
      neuroanatomical and clinical training of the type that only you can give". On the
      other hand, Brouwer sent several Amsterdam pupils and Dutch colleagues to New
      Haven. From the correspondence, we learn that there was a vivid exchange of
      neuroscientific knowledge by books, letters, reprints and pupils. The
      correspondence demonstrates the changing dynamics of scientific exchange between
      Europe and America.

PMID- 12785115
TI  - Reissner's fibre: the exception which proves the rule, or the devil according
      Charles Baudelaire?

PMID- 12785116
TI  - An autobiographical sketch.

PMID- 12785117
TI  - Neurological eponyms--who gets the credit? Essay review.
AB  - The recent publication of Neurological Eponyms by Peter Koehler and colleagues
      has revived the interest in neurological eponyms and raised important questions
      about their use. Many investigators have contributed to the body of knowledge
      that defines the specialty of neurology. We honor them by associating their names
      with neurological diseases. The history of neurological eponyms provides us with
      an opportunity to reexamine the important question of who gets the credit.
      Additional issues have surfaced including why certain eponyms tend to stick in
      the literature and others disappear, as well as the important realization that
      lengthy modern descriptions may require name eponyms for simplification. Eponyms
      can be confusing as to whether they refer to a disease or a syndrome and this
      confusion can impact the diagnosis and treatment of patients. There is an
      inevitable evolution of certain eponyms as our understanding of entities expands.
      This paper provides an overview of neurological eponyms with the explanation of
      the potential reasons why names were associated with neurological diseases. These
      included first case reports, relating isolated cases, years of observation,
      defining neuroanatomy, physician sufferer, new physical examination maneuvers,
      academic climate, the advent of a new procedure, fame, and competition amongst
      investigators. Important issues have surfaced regarding sharing credit amongst
      investigators, name priority, crediting the wrong investigator, and lack of a
      defined system to award credit. Since eponym use is based on a peer dependent
      system, each neurologist must make a more critical appraisal of who gets the
      credit and understand the differences between diseases and syndromes in order to
      better preserve neurological history.

PMID- 12785118
TI  - Comparison of behavioural effects of venlafaxine and imipramine in rats.
AB  - The experiments outlined in this paper examined the effects of the novel
      antidepressant venlafaxine (VEN) (CAS 9930-78-4) in several behavioural and
      memory tests in comparison with the classic antidepressant imipramine (IMI) (CAS
      113-52-0). The tests were carried out on male Wistar rats of about 200 g. The
      drugs were administered orally 30 min before the tests during 14 days. The aim of
      the locomotor activity test was to select the doses without influence on the
      motility of the animals and active at least in two behavioural tests. Such dose
      was 20 mg/kg b.w. for both drugs--VEN and IMI. In the immobility test, which
      reflects antidepressant drug activity, the following differences were found: VEN
      shortened immobility time (IT) on days 1 and 7 (no activity on day 14), whereas
      IMI shortened IT on days 7 and 14 and displayed no activity on day 1. In the two
      compartment exploratory test both drugs displayed distinct anxiolytic effect on
      days 1 and 7, yet on day 14 only IMI was still active. In the maze test only VEN
      shortened food finding time on day 1, on day 7 and on day 14 during chronic
      treatment. IMI was inactive in the maze test. The authors conclude that the
      general pattern of VEN activity is similar to that of IMI, but in some tests,
      especially in the memory test, the new drug is superior to IMI.

PMID- 12785119
TI  - Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis
      viniferae) in the treatment of chronic venous insufficiency. A 6-week
      observational clinical trial.
AB  - The characteristic components of the pure plant-based extract AS 195 (Folia vitis
      viniferae) are flavon(ol)-glycosides and glucuronides with quercetin-3-O-beta-D
      glucuronide (main flavonoid) and isoquercitrin (quercetin-3-O-beta-glycoside; a
      secondary flavonoid). In previous clinical studies AS 195 (hard gelatine
      capsules) has shown oedema-preventing and subjective symptoms alleviating
      properties in patients with chronic venous insufficiency (CVI). The aim of the
      present open-label, multicentre, observational trial was to assess tolerability
      and efficacy of AS 195 (Antistax film-coated tablets). The reduction of the
      subjective CVI-related symptoms was measured on a 10-cm visual analogue scale.
      For the global assessment of efficacy and tolerability by the patient and the
      investigator a 4-point verbal rating scale was used. Sixty-five male and female
      patients aged 25-82 years with CVI grade I or II (Widmer classification) received
      AS 195, two film-coated tablets once daily for 42 days (360 mg/day). At the end
      of the study, all subjective symptoms of CVI (tired, heavy legs, sensation of
      tension in the legs, tingling sensations in the legs, pain in the legs) were
      statistically significantly improved. The global assessment of efficacy by the
      patients and by the investigators was rated as good or satisfactory in most of
      the patients. AS 195 filmcoated tablets were very well tolerated during the whole
      trial, as their global tolerability was assessed for most patients as good or
      satisfactory by both the patients and investigators. Six patients experienced
      adverse events potentially causally related to trial medication. Four of them
      reported gastrointestinal problems. The present study showed a marked improvement
      of subjective symptoms associated with CVI grade I or II, as well as a good or
      satisfactory global assessment of efficacy and tolerability by the patients and
      the investigators. Thus, AS 195 film-coated tablets can be considered as
      effective and safe in patients with CVI grade I or II.

PMID- 12785120
TI  - [Conjugation reactions of ciprofibrate with human and laboratory animals].
AB  - An open problem of the lipid lowering agent ciprofibrate (rac-2-[4-(2,2
      dichlorocyclopropyl)-phenoxy]-2-methylpropanoic acid, CAS 52214-84-3) is its
      metabolism concerning the conjugation with amino acids and glucuronic acid. It
      could be solved by syntheses of the needed reference compounds--unknown up to now
      -and administration of ciprofibrate to volunteers and rats. Unexpectedly the
      conjugation compounds with amino acids are stable in vitro and in metabolism.
      There was no evidence for any conjugation reaction with amino acids by
      investigating samples of urine and faeces. On the contrary the urine of humans
      contains 90-97% of beta-O-acylglucuronide, whereas rat urine shows only 10% of
      the calculated amount.

PMID- 12785121
TI  - Determination of antioxidant activity of some drugs using high-pressure liquid
      chromatography.
AB  - The antioxidant activities of different drugs like acetylsalicylic acid,
      nimesulide, dapsone, methlydopa, rifampicin and the well known antioxidants
      ascorbic acid and quercetin were assessed using the stable free radical
      alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH). DPPH is easily soluble at lower
      concentrations in methanol. It has a deep violet color. The changes in color are
      monitored calorimetrically. The measurements were made using HPLC at wavelengths
      256 nm and 517 nm. The interactions between different drugs with DPPH were
      studied. All the compounds tested reduced DPPH. This method can be used to
      investigate oxygen free radical scavenging activity of drug candidates.

PMID- 12785122
TI  - Pharmacokinetic interaction study of a fixed combination of 500 mg
      acetylsalicylic acid/30 mg pseudoephedrine versus each of the single active
      ingredients in healthy male volunteers.
AB  - Acetylsalicylic acid (CAS 50-78-2, ASA) and pseudoephedrine (CAS 90-82-4, PSE)
      both are remedies given together for the treatment of the symptoms of a common
      cold, i.e. mainly nasal congestion, running nose, sore throat and headache. The
      aim of this open, randomized, three-factorial (three-treatment, three-period, six
      sequence) Latin Square clinical study was to investigate if there were any
      pharmacokinetic interactions between ASA and PSE when given as fixed combination
      of 500 mg ASA/30 mg PSE.HCl. Lack of interaction was assessed by determination of
      pharmacokinetic characteristics and relative bioavailability of both substances
      and salicylic acid (CAS 69-72-7, SA), administered in combination and as equally
      single dosed drugs. In total, the data of 12 healthy male volunteers were
      included into the pharmacokinetic evaluation. Primary target parameters were
      ratios combination/equally dosed single drugs of AUCnorm and Cmax, norm of ASA,
      its metabolite SA and PSE. The primary target parameters were analyzed using an
      analysis of variance (ANOVA) after logarithmic transformation of the data. 90%
      confidence intervals were calculated for the geometric means of ratios using the
      mean square error term of the ANOVA. RESULTS: Bioequivalence was given for
      AUCnorm and Cmax, norm for all ratios calculated. No interaction was found for
      AUCnorm and Cmax, norm between the fixed combination ASA/PSE and the equally
      single dosed drugs as reference. The supplementary evaluation for the non
      normalized original parameters AUC and Cmax also revealed bioequivalence. All
      treatments were safe and well tolerated.

PMID- 12785123
TI  - Synthesis and HIV-1 reverse transcriptase inhibitor activity of some 2,5,6
      substituted benzoxazole, benzimidazole, benzothiazole and oxazolo(4,5-b)pyridine
      derivatives.
AB  - In this study, the synthesis of some benzoxazoles and their analogues were
      described and their antiviral activities were studied together with the
      previously synthesized 2,5,6-trisubstituted benzoxazole, benzothiazole,
      benzimidazole and oxazolo(4,5-b)pyridine derivatives. The reverse transcriptase
      (RT) inhibitory activity of these compounds was determined using a commercial kit
      and assay system which utilizes the scintillation proximity assay principle. The
      results are concentration at which the compound inhibits RT activity by 50%). The
      compounds inhibited the in vitro binding of thymidine to the RT enzyme exhibiting
      IC50 values between 6.3 x 10(5) mumol/l-0.34 mumol/l and their activities were
      compared to some standard drugs such as 3'-azido-2',3'-dideoxythymidine
      triphosphate and dideoxythymidine triphosphate.

PMID- 12785124
TI  - Safety pharmacology of CKD-602, a novel anticancer agent.
AB  - CKD-602 ((20S)-7-[2-(N-isopropylamino)-ethyl]-camptothecin.HCl, CAS 213819-48-8)
      is a new class of anticancer drug that belongs to the topoisomerase inhibitors.
      Its effect on the central nervous system (CNS), general behavior, cardiovascular
      respiratory system and the other organ systems were studied. When intravenously
      administered, CKD-602 up to doses of 5 mg/kg caused an increase of body
      temperature, increase of respiration rate, decrease of gastrointestinal
      transport, showed analgesic action and produced antisecretory action in pylorus
      ligated rats. However, CKD-602 showed no effects on general behavior, motor
      coordination, spontaneous locomotor activity, hexobarbital sleeping time,
      convulsion, cardiovascular, smooth muscle and urinary tract system. These
      findings demonstrate that CKD-602 in doses up to 5 mg/kg has minor effects on the
      CNS in animals. However, CKD-602 does not exert any general pharmacological
      effects at the dose of 1 mg/kg except the effects on gastric secretion.

PMID- 12785125
TI  - Antifungal properties of novel N- and alpha,beta-substituted succinimides against
      dermatophytes.
AB  - The synthesis and antifungal properties of a series of new N-aryl alpha,beta
      substituted succinimides against a panel of dermatophytes of clinical relevance
      are reported. Among those compounds possessing a N-phenyl substituent, 7-thia-2
      azabicyclo[2,2,1]hept-2-en-3-amine[5,6-c]succinimide was the better inhibitor of
      Trichophyton rubrum, the major ethiological agent of all infections produced by
      dermatophytes. In contrast, succinimides containing a N-(p-sulfonylphenyl)
      substituent, only inhibited Epidermophyton floccosum, all active compounds
      possessing an oxabicyclo group in positions alpha,beta of the imide. Substituents
      on the oxabicyclo group were important for the activity. Regarding the mechanism
      of action, N-(p-N'-4-methoxyphenylsulfamoylphenyl)-8-oxabicyclo[2,2,1]hept-4-en-3
      methyl[5,6-c]succinimide produced a mottled inhibition halo in the Neurospora
      crassa assay, showing that it would act by inhibiting the synthesis or assembly
      of the fungal cell wall.

PMID- 12785126
TI  - Clinical relevance of bioequivalence acceptance criteria. The example of
      terbinafine.
AB  - OBJECTIVE: The present study was conducted with the aim of investigating which
      acceptance criteria for bioequivalence are relevant for orally applied
      antimycotics using terbinafine (CAS 78628-80-5) as an example. METHODS: A
      bioequivalence trial was performed in 18 healthy male volunteers with the aim of
      comparing a new generic product (tablets containing terbinafine hydrochloride,
      equivalent to 250 mg base) with the originator product. The trial was performed
      according to an open, cross-over design in one study centre. In each of the two
      study periods (separated by a wash-out of 14 days) a single dose of one 250 mg
      tablet (test or reference) was administered. Blood samples were taken up to 72 h
      post dose, the plasma was separated and the concentrations of terbinafine were
      determined by a liquid chromatography-mass spectrometry (LC-MS-MS) method with a
      quantification limit of 14 ng/ml. AUC0-infinity, AUC0-tlast, Cmax and tmax were
      calculated for both formulations and compared according to the currently valid
      CPMP Note for Guidance for the evaluation of Bioavailability and Bioequivalence.
      RESULTS: The parametric 90% confidence intervals for the primary target
      parameters were between 0.89 and 1.09 AUC0-tlast and between 0.71 and 0.95 for
      Cmax. The acceptance ranges prospectively defined in the protocol for this trial
      were fulfilled. In the light of the currently valid CPMP Note for Guidance, the
      question still arose whether the overall positive bioequivalence statement was
      clinically feasible. Taking into account the mechanism of action and the
      available efficacy and safety data on terbinafine, this question was answered
      positively. CONCLUSION: In the case of oral antimycotic agents and especially
      terbinafine, the bioequivalence acceptance range for Cmax can be expanded to 0.7
      1.43, if the acceptance criteria for AUC are fulfilled.

PMID- 12785127
TI  - The need for reappraisal of type 2 diabetes mellitus management.
AB  - Type 2 diabetes is a multiorgan disease that results from the combination of
      insulin resistance and a beta-cell secretory defect. Because the complications
      associated with this disease are so significant, the importance of lowering
      glycosylated hemoglobin levels to within the normal range cannot be
      overemphasized. Thiazolidinediones (TZDs) modulate lipid metabolism, improve
      insulin sensitivity, exert numerous nonglycemic effects on the vasculature and
      lipid metabolism, and may improve many risk factors associated with the metabolic
      syndrome. Data from the UK Prospective Diabetes Study showed that conventional
      methods of managing type 2 diabetes, including sulfonylureas and biguanides, do
      not provide long-term glycemic control. Consequently, new treatment paradigms
      stressing earlier use of TZDs may lead to more durable glycemic control,
      facilitating the reduction of complications in patients with type 2 diabetes.

PMID- 12785128
TI  - Lessons learned from landmark trials of type 2 diabetes mellitus and potential
      applications to clinical practice.
AB  - Landmark studies have demonstrated that diabetes is a significant risk factor for
      cardiovascular disease and mortality. Strong relationships exist between insulin
      resistance/hyperglycemia and mortality, microvascular complications, and
      cardiovascular complications. Lipid abnormalities frequently associated with type
      2 diabetes and insulin resistance include low high-density lipoprotein
      cholesterol (HDL-C) and elevated triglyceride levels. Lowering low-density
      lipoprotein cholesterol levels has been shown to improve the prognosis of
      patients with diabetes, and increasing HDL-C levels will significantly reduce the
      incidence of major coronary events. Higher levels of insulin sensitivity are
      associated with thinner intimal-medial thickness of the carotid artery, which
      indicates less atherosclerosis. Thiazolidinediones increase insulin sensitivity,
      decrease intimal-medial thickness, and appear to have inhibitory effects on the
      progression of atherosclerotic lesions. It is hoped that by preventing the onset
      of diabetes in high-risk individuals--and improving insulin sensitivity with
      lifestyle changes or pharmacologic treatment--the profound complications of type
      2 diabetes will be prevented or delayed, as well.

PMID- 12785129
TI  - Insulin resistance syndrome. Description, pathogenesis, and management.
AB  - The insulin resistance syndrome is composed of risk factors for cardiovascular
      disease, including insulin resistance with hyperinsulinemia, atherogenic
      dyslipidemia, hypertension, abdominal obesity, and impaired hemostasis. Patients
      with type 2 diabetes frequently manifest multiple risk factors for cardiovascular
      morbidity and mortality. Management of the insulin resistance syndrome often
      includes antihypertensive, lipid-lowering, and antihyperglycemic agents. Because
      thiazolidinediones (TZDs) directly improve insulin resistance, early use may
      provide substantial benefits to patients with type 2 diabetes. TZDs reduce plasma
      glucose and insulin concentrations, promote relocation of body fat, and have anti
      inflammatory effects on the vascular endothelium. Combination oral hypoglycemic
      therapy may be ideal for maintaining adequate glycemic control in patients with
      type 2 diabetes. The combination of a TZD and a biguanide, which improves insulin
      sensitivity and lowers blood glucose through different pathways, offers
      significant benefits and may help prevent or delay prevent complications
      associated with type 2 diabetes.

PMID- 12785130
TI  - Beneficial effects resulting from thiazolidinediones for treatment of type 2
      diabetes mellitus.
AB  - Because new drugs continue to be developed, physicians treating patients with
      type 2 diabetes have a wide range of agents from which to choose. The newest
      class, the thiazolidinediones (TZDs), should be a mainstay of treatment for most
      patients with type 2 diabetes, because these agents reduce insulin resistance as
      well as improve glycemic control. Patients with the insulin resistance syndrome
      are at increased risk for developing cardiovascular disease. However, decreasing
      insulin resistance with TZD use may reduce the incidence of adverse
      cardiovascular outcomes. TZDs also may reduce cardiovascular events by acting
      directly on vascular smooth muscle cells and by helping patients maintain normal
      hemoglobin levels, without the risk of hypoglycemia. Furthermore, prolonged
      glycemic control is expected with TZDs because of their effects on beta-cell
      rejuvenation, a function unique to this class. TZDs can be used safely in renally
      impaired patients with diabetes, and hepatotoxicity has not been a problem with
      second-generation TZDs, making these agents both safe and effective in the
      treatment of type 2 diabetes.

PMID- 12785131
TI  - Cardiovascular disease and benefits of thiazolidinediones.
AB  - Thiazolidinediones (TZDs) directly improve insulin resistance and appear to
      preserve beta-cell function. Research has demonstrated beneficial changes in
      several cardiovascular risk factors, including decreased levels of proinsulin,
      free fatty acids, diastolic blood pressure, and microalbuminuria, as well as
      improvement in lipid parameters. TZDs decrease plasminogen activator inhibitor
      type 1, inhibit vascular smooth muscle cell proliferation, reduce carotid artery
      intimal-medial thickness, and improve endothelial function. These actions
      directly improve the vasculature and should decrease cardiovascular risk.
      Atherosclerosis is an inflammatory process, and TZDs reduce inflammatory markers,
      such as C-reactive protein, monocyte chemoattractant-1, and p47phox. The data
      suggest that TZDs may reduce the risk of cardiovascular disease when used in
      patients with type 2 diabetes.

PMID- 12785132
TI  - Process improvement approach to the care of patients with type 2 diabetes.
      Providing physicians with tools to increase compliance and improve outcomes.
AB  - Diabetes care relies on patient/physician-initiated programs of periodic
      evaluation, monitoring, and treatment interventions. Clinical practice guidelines
      can assist clinicians in diabetes care. To improve outcomes, these methods must
      be designed and implemented in a way that promotes change in physician behavior.
      When guidelines are corrected to real-time reminder protocols (at the time the
      physician is making clinical decisions with the patient), compliance with
      recommended tests and procedures is increased. Follow-up analysis of performance
      and comparison with peers assists physicians in making the necessary clinical
      interventions that improve the management of these conditions and reduce
      complications. Integrated electronic medical records are a key initial component
      for motivating physicians and initiating effective diabetes management plans.

PMID- 12785133
TI  - Constructing an algorithm for managing type 2 diabetes. Focus on role of the
      thiazolidinediones.
AB  - With the understanding of type 2 diabetes mellitus constantly evolving, and with
      the introduction of many new agents during the past few years, it is often
      difficult to keep up to date with the management of type 2 diabetes. This article
      reviews the pathophysiology of type 2 diabetes, oral pharmacologic treatment, and
      proposed diabetes treatment algorithms, which aim to guide clinicians in the use
      of thiazolidinediones (TZDs) earlier in the course of diabetes. This is important
      because studies indicate that sulfonylureas, biguanides, and insulin do not
      protect the beta cell and cannot provide sustainable glycemic control. The basis
      for TZD use earlier in diabetes is 2-fold: to preserve beta-cell function while
      maintaining appropriate glycemic control for a longer duration than is usually
      attained through monotherapy with a secretagogue or biguanide, and to prevent or
      reverse the insulin resistance phenomenon of reduced insulin utilization that
      appears even prior to the clinical diagnosis of diabetes. Notably, decreasing
      insulin resistance also may reduce the incidence of adverse atherosclerotic
      consequences.

PMID- 12785134
TI  - OSHA bloodborne pathogens rule--revisions and clarifications.
AB  - Recent revisions to the Occupational Safety and Health Administration's
      Bloodborne Pathogens Rule have clarified requirements for record keeping and
      engineered sharps injury protection devices. It is important for dental workers,
      and especially dentists who are employers, to be aware of the changes in the
      regulatory language and be prepared to modify existing programs to meet these new
      demands. This article provides an overview of the 2001 Bloodborne Pathogens Rule
      with an emphasis on the impact on dental offices.

PMID- 12785135
TI  - The truth about dental insurance--Part II.

PMID- 12785137
TI  - Single-visit vs multiple-visit endodontics: which is best?

PMID- 12785136
TI  - Bloodborne pathogens: current concepts.
AB  - In the early 1980s, the AIDS hysteria began to gain momentum. As a direct result
      of this phenomenon, the delivery of dental care changed dramatically. By 1989,
      most dentists had begun to accept the concept of universal precautions and
      compliance with infection control recommendations from the Centers for Disease
      Control and Prevention and the Organization for Safety & Asepsis Procedures. The
      emergence of bloodborne pathogens from the 1970s has been a significant milestone
      in the history of the dental profession. Patients infected with human
      immunodeficiency virus, hepatitis B virus, and hepatitis C virus are commonly
      encountered in the modern dental practice, and dental providers need to have a
      thorough knowledge about bloodborne diseases and the dental management of
      patients presenting with these diseases.

PMID- 12785138
TI  - Dental waterlines and biofilm--searching for solutions.
AB  - This article reviews the nature of aquatic biofilms in dental waterlines and
      their effect on the quality of water used in dental treatment. Also addressed is
      the current state of knowledge about the health consequences of microbial
      contamination of dental treatment water and the evidence basis for various
      treatment options. The rationale for treatment of dental water systems and
      criteria for selection of products are discussed.

PMID- 12785139
TI  - Ergonomics: muscle fatigue, posture, magnification, and illumination.
AB  - Chronic low-level trauma very often goes unnoticed until symptoms prompt
      sufferers to seek medical help. Many combined risk factors, rather than a single
      event or practice, lead to cumulative trauma disorders. Muscle fatigue leads to
      muscle trauma as well as a cascade of other injuries. With preemptive ergonomic
      strategies, such as the use of magnification and illumination, many of the common
      disabilities associated with dental careers can be avoided or reduced. The
      information in this article is of particular interest to not only the practicing
      dentist, but the entire dental team.

PMID- 12785140
TI  - The rubber dam--a first step toward clinical excellence.

PMID- 12785141
TI  - Volunteers for Israel: Sar-El, "helping hands".

PMID- 12785142
TI  - Dentistry in the Amazon.

PMID- 12785143
TI  - The Greater Hartford alumni chapter and the excavations at Qumran.

PMID- 12785144
TI  - Selecting medical gloves in an era of latex protein allergy.

PMID- 12785145
TI  - What you don't know will hurt you; it already has!

PMID- 12785146
TI  - Polio eradication and the Rotary connection.

PMID- 12785147
TI  - Collection: are you afraid to ask for money?

PMID- 12785148
TI  - Create a magnetic healthcare workplace: preview of a pre-convention workshop on
      nurse retention for healthcare leaders.

PMID- 12785149
TI  - Preparing future leaders.

PMID- 12785150
TI  - Leader as visionary. Leadership education model.
AB  - Developing nurse leaders for today and tomorrow is a priority considering the
      powerful relationship between leadership strength and the influence of the
      nursing profession in the future of health care. This article addresses
      leadership theories and research as they relate to visionary leadership.
      Education for visionary leadership is also addressed including the competencies
      and skill sets for effective visionary leaders. Visioning is a powerful force for
      change in shaping organizations and building teams for the future.

PMID- 12785151
TI  - Leader as expert.
AB  - A rapidly changing and uncertain health care delivery system requires well
      educated nurse leaders who can work to achieve organizational missions that are
      appropriate for the needs of all who seek health care. Educators in both
      undergraduate and graduate programs can use the four ways of knowing as outlined
      by Carper (1978) to design curricula that will prepare nursing leaders as
      experts.

PMID- 12785152
TI  - Leader as achiever.
AB  - This article examines one outcome of leadership: productive achievement. Without
      achievement one is judged to not truly be a leader. Thus, the ideal leader must
      be a visionary, a critical thinker, an expert, a communicator, a mentor, and an
      achiever of organizational goals. This article explores the organizational
      context that supports achievement, measures of quality nursing care, fiscal
      accountability, leadership development, rewards and punishments, and the
      educational content and teaching strategies to prepare graduates to be achievers.

PMID- 12785153
TI  - Leader as critical thinker.
AB  - A leader possess the critical-thinking knowledge and skills that provide the
      framework from which complex problem solving evolves. This article explores the
      leader as critical thinker, including a progressive plan for integrating critical
      thinking concepts and associated teaching strategies into the RN to BSN and
      graduate curricula. To improve the critical thinking of nurses, educators must
      emphasize the cognitive and disposition aspects of critical thinking; promote
      active and sequential learning; role model critical thinking; design practical
      that focus on leadership and critical thinking; and conduct valid and consistent
      evaluations. The acquisition and application of critical thinking and problem
      solving skills are progressive and refined through life-long learning and
      experience. This expertise begins with a sound knowledge base of the critical
      thinking composite and problem-solving strategies.

PMID- 12785154
TI  - Leader as communicator.
AB  - This article examines common communication factors that have an impact on leader
      effectiveness (language, listening, mode of delivery, and feedback) and the role
      of the organization, organizational culture, and group dynamics in the
      development of the leader as a communicator. Communication, like any skill, is a
      learned behavior that is honed over time. Communication is a two-way process with
      stimulus-response shaping future behavior. But, it is even more complex when used
      in an organizational setting because there are multilevel communications,
      multiple message, senders and receivers, and competing agendas. Leaders in
      today's complex health care organizations must be skilled communicators to earn
      trust and respect. Once trust and respect have been earned, others are willing to
      listen to the leader's vision and to help make it a reality because, done well,
      it demonstrates expertise, critical thinking, achievement, and mentoring
      abilities.

PMID- 12785155
TI  - Leader as mentor.
AB  - A key component of leadership development for nursing students is mentorship.
      Leaders are called to be developers of others and to grow the next generation of
      leaders. Through the teaching-learning role and through serving as active mentors
      with students, leader-teachers can promote leadership skill development and
      leadership succession in the profession. Teaching the mentor concept as part of
      leadership occurs through student-teacher relationships, in the classroom, and in
      practicum experiences. Research and anecdotal studies are needed that illustrate
      curricular, course, and programmatic inclusion of mentorship and the benefits and
      outcomes of this educational approach to leadership development.

PMID- 12785156
TI  - Uses and disclosures of protected health information: "consent" and
      "authorization".

PMID- 12785157
TI  - Lactate--a diagnostic indicator.

PMID- 12785158
TI  - Focal segmental glomerulosclerosis in childhood: histology, glomerular
      morphometry, electron microscopy and immunofluorescence findings in biopsies
      performed early in the course of the disease.
AB  - The histological evolution of Focal Segmental Glomerulosclerosis (FSGS) is poorly
      documented due to variation in the time at which the biopsy is taken. We looked
      at patients presenting with steroid resistant nephrotic syndrome (SRNS) in which
      the first biopsy was performed within 3 months of presentation. FSGS lesion was
      demonstrable in 68.5% of cases in the first biopsy. Glomerular size was increased
      in 86% of patients indicating that is an early event in the course of the
      disease. The group was heterogenous with respect of mesangial cellularity,
      mesangial matrix, position of FSGS lesion in the glomeruli, glomerular size,
      lamina densa thickness and immunofluorescence findings. No association of
      morphological features was seen permitting subclassification of this group on
      morphological grounds. Thus, both the FSGS lesion and glomerular enlargement
      occur early in the evolution of idiopathic FSGS presenting with SRNS.

PMID- 12785159
TI  - Role of fine needle aspiration cytology in the diagnosis of palpable thyroid
      lesions.
AB  - Fine needle aspiration cytology is now recommended as the first choice for the
      evaluation of palpable thyroid nodules. A total of 170 fine needle aspirates of
      thyroid were evaluated in which the subsequent biopsy were also available for
      histopathological examination. The age ranged from 16 to 70 years. The
      cytological diagnosis were compared with the histological results which revealed
      the sensitivity of 61.90% and 80.95%, the specificity of 99.31% and 76.55%,
      positive predictive value of 92.86% and 33.33%, negative predictive value of
      94.74% and 96.52% and accuracy index of 94.58% and 77.11% were found, when
      considering suspicious cases alternatively as positives and negatives. Similar
      statistics from other series of studies revealed almost same results in which
      cytological results of thyroid lesions were compared with histological results.
      This suggests that FNAC is an effective and accurate technique for the diagnosis
      and further management of palpable thyroid nodules.

PMID- 12785160
TI  - Role of mitotic counts in the grading and prognosis of the breast cancer.
AB  - 100 Cases of invasive breast cancer were studied for Tumor type, Tumor site,
      Nodal Status, Mitotic counts, Nuclear pleomorphism, Tubule formation and
      Nottingham modification of Bloom Richardson Grading. The follow up of the 82
      patients treated with surgery and adjuvant treatment was available. Mitotic
      activity index (MAI) counted with strict criteria of elston CW, emerged as one of
      the most significant prognostic parameter followed by overall grade in predicting
      Tumor free survival (TFS) for the patients. Mitotic count also correlated well
      with overall Grade and lymph node status in predicting the TFS. This parameter is
      very useful where advanced studies like flowcytometry and immunohistochemical
      studies of the cell proliferation marker are not available.

PMID- 12785161
TI  - Evaluation of adnexal masses by ultrasound and fine needle aspiration cytology.
AB  - Forty Eight cases of adnexal masses were subjected to ultrasound and FNAC. In
      this study, FNAC could differentiate benign and malignant adnexal masses in 98%
      of cases where as ultrasound was successful in 85% of cases. FNAC is a safe
      simple, rapid & reliable investigation. The complex adnexal masses present a
      diagnostic challenge with particular reference to the findings predictive of
      malignancy.

PMID- 12785162
TI  - Significance of mucin secretion in carcinoma of uterine cervix.
AB  - Biopsies from 300 cases with clinical diagnosis of carcinoma cervix were
      subjected to H&E staining, PAS with diastase and alcian blue at pH 2.5.
      Interpretation of cases on basis of H&E staining alone and on basis of H&E and
      mucin stains was done and results compared with each other. Categorization into
      squamous cell carcinoma (well, moderately & poorly differentiated),
      adenocarcinoma and mixed carcinoma was done. Morphologic assessment of cases of
      H&E stain revealed 282 (94%) cases of squamous cell carcinoma, 8 (2.66%) cases of
      adeno carcinoma and 10 (3.38%) cases of mixed carcinoma respectively. While on
      the basis of H&E and mucin stains, squamous cell carcinoma case turned out to be
      266 (88.66%) in number; mixed carcinomas which included adenosquamous carcinoma
      and squamous cell carcinoma with mucin secretion accounted for 26 (8.66%) of
      cases, number of adenocarcinoma was unchanged i.e. 8 (2.66%). 16 of 282 cases
      (5.6%) diagnosed as squamous cell carcinoma on H&E stain alone were reclassified
      as mixed carcinoma on inclusion of mucin stains. Thus mucin stains are very
      helpful in deciding the types of carcinoma cervix and should be done in all cases
      of carcinoma cervix in order to avoid errors in diagnosis and to detect poorly
      differentiated mixed carcinomas, which may escape detection by H&E staining.

PMID- 12785163
TI  - NESTROFF as a screening test for detection of Beta-thalassemia trait.
AB  - Naked Eye Single Tube Redcell Osmotic Fragility Test (NESTROFT) was applied to
      110 patients of suspected cases of beta-Thalassemia and other
      haemoglobinopathies. Out of 110 patients, 10 cases were of beta-Thalassemia
      major, 35 of Thalassemia minor and 65 of sickle cell disease. The study was
      carried out to evaluate the effectiveness of NESTROFT as a screening test for
      beta-Thalassemia trait. The test was successful in detecting 34/35 subjects with
      beta-Thalassemia trait. Sensitivity of the test was 97.1% and specificity was
      100%. The test was positive in detecting other haemoglobinopathies like sickle
      cell disease also. The test proved to be simple, cheap easy to perform and
      adaptable for mass screening coming close to an ideal screening test for beta
      Thalassemia trait.

PMID- 12785164
TI  - Role of viral serology in the diagnosis of acute retinal necrosis syndrome.
AB  - Due to the devastating nature of acute retinal necrosis syndrome (ARNS), early
      diagnosis is essential. 5 cases of clinically diagnosed ARNA were investigated
      for CMC, herpes simplex and varicella zoster virus (VZV) infections. Of the three
      VZV IgM positive cases, two were positive in acute blood samples and one in
      vitreous fluid. Thus VZU can be incriminated as the causative agent of ARNS cases
      in North India.

PMID- 12785165
TI  - Secondary malignant giant cell tumour of bone--a study of five cases with short
      review of literature.
AB  - Secondary malignant giant cell tumour of bone occurs as a result of previous
      attempts at local control of a benign giant cell tumour of bone (GCT). Out of the
      total 445 conventional benign GCT of bone, therapeutic irradiation was given in
      39 cases as the lesions were located in the vertebrae and pelvic bones where
      debulking surgery was not possible and the tumours were pressing on the spinal
      cord. The patients were followed up for 21 years. Out of 39 cases, 5 patients
      developed sarcomas of which 3 were fibrosarcomas, 1 was malignant fibrous
      histiocytoma while 1 was an osteosarcoma. All the patients developing post
      radiation sarcomas died within a few months due to lung metastasis. In
      conclusion, all the patients with benign GCT of bone treated with radiation must
      be followed life long as they are prone to develop sarcomas.

PMID- 12785166
TI  - Quality assessment program in histopathology: a pilot study from Maharashtra.
AB  - Histopathology reports are important quality assurance tools and evaluation of
      pathological diagnoses described in them is an integral part of total quality
      control and quality improvement program. We describe a program based on slide
      circulation which was aimed at both continuing education to upgrade knowledge and
      proficiency testing of histopathologists. The performance of the participating
      pathologists was analyzed and the degree of agreement was also studied. The
      results showed improvement indicated by rising level of performance in 35.3% of
      consistent participants and increasing trend in the average score. The degree of
      agreement was comparatively low (65.29%). The practicability of this program and
      its acceptability as an EQAS was also investigated.

PMID- 12785167
TI  - Expression of bcl-2 oncoprotien in oral squamous cell carcinoma--an
      immunohistochemical study.
AB  - Squamous cell carcinoma is the most common malignant neoplasm of the oral cavity.
      Number of mechanisms plays a role at the molecular level to transform normal cell
      into a neoplastic cell. There are a gamut of genes, which are expressed among
      which bcl-2, have gained a unique importance as inhibitor of apoptosis. In normal
      epithelial cells Bcl-2 is restricted to stem cells and cells which undergo
      mitosis. Bcl-2 blocks the post-mitotic phase from apoptosis. Reports of Bcl-2
      protein expression in carcinomas are conflicting such as down regulation to
      elevated expression. In the present study 67 cases of squamous cell carcinomas of
      varying grades were studied and uniform cytoplasmic positivity were noted in 12
      cases for Bcl-2 protein. Bcl-2 prolongs cell survival in epithelial cells and
      there by giving way to other external stimulus like action of carcinogens and
      viral agents and interaction with other genes and aids in progression to
      neoplasia. The possible roles of bcl-2 in the pathogenesis of oral squamous cell
      carcinoma are discussed.

PMID- 12785168
TI  - Evaluation of AgNORs in pulmonary lesions: a cyto-histopathological correlation.
AB  - Silver nucleolar organizer regions (AgNORs) were studied in one hundred specimens
      of endobronchial brushings. Bronchial biopsies were also obtained from these one
      hundred cases and subjected to AgNOR staining. These included twenty
      histologically normal cases, ten cases of inflammatory pathology and seventy
      cases of pulmonary neoplasms. Fixed cytologic smears and three micron thick
      sections of paraffin embedded tissue were subjected to AgNOR staining. The mean
      AgNOR counts in bronchial tissue showed a progressive and statistically
      significant increase from normal, through inflammatory to neoplastic lesions in
      both cytologic smears and histopathologic specimens. The AgNOR technique is
      simple, inexpensive and a useful adjunct to routine histopathology, to evaluate
      pulmonary lesions. The counts, however, cannot be standardized for a particular
      lesion as there are inter-laboratory variations.

PMID- 12785169
TI  - Spectrum of dermatopathologic lesions associated with HIV/AIDS in India.
AB  - Histopatholgoical analysis of cutaneous lesions in 195 patients with HIV/AIDS was
      carried out between 1989 to 1997 at tertiary level public hospital in Mumbai.
      104/195 (53%) cases showed infectious diseases which comprised of molluscum
      contagiosum (28), condyloma accuminata (18), verruca vulgaris (7), varicella
      zoster (5), syphilis (14), tuberculosis (13), donovanosis (4), leprosy (2),
      chancroid (2), bacillary angiomatosis (2), lymphogranuloma venercum (1),
      Norwegian scabies (3), leishmaniasis (2), demodicidosis (1), crytococcosis (1),
      tinea versicolor (1). In 12 (6%) cases neoplasms were observed which included
      squamous cell carcinoma (9), basal cell carcinoma (2) and kaposi's sarcoma (1)
      case. The miscellaneous conditions were observed in 66(33.5%) cases which
      comprised of psoriasis (21), papular urticaria (13), Reiter's disease (7) and
      eosinophilic folliculitis (6). The prevalence of cutaneous tuberculosis observed
      in this study is high as compared with western literature while the prevalence of
      kaposis's sarcoma is quite low as compared with reports from Africa, USA and
      United Kingdom.

PMID- 12785170
TI  - A study of keratomycosis: our experience.
AB  - The aim of the present study was to determine the etiological agents,
      predisposing factors and important diagnostic tests in keratomycosis in Patna.
      During period of 2 years, 204 clinically suspected cases of keratomycosis were
      studied by microscopy (10% KOH smear preparation and Gram's staining) and culture
      (for bacteria as well as fungus). Out of 204 clinically suspected cases, 76 cases
      (37.23%) were reported positive for fungus by microscopy and culture. 77% cases
      were between the age group of 21 to 50 years. Males were more than double the
      number of females affected. 82% patients were farmers by occupation. 81.58% cases
      gave a definite history of antecedent corneal trauma. 6.58% cases were known
      diabetics. Peak incidence was recorded in the months of September-October of the
      years. Single fungal isolates were present in 63 cases (31%) and multiple were
      there in 3 cases (1.47%). Mixed isolates of bacteria and fungi were there in
      4.90% cases. The predominant isolate was Aspergillus species--42 cases (52.26%)
      followed by Candida--7 cases (9.21%), Penicillium--6 cases (7.89%) and Fusarium-6
      cases (7.89%). Ten (13.15%) of fungal isolates remained unidentified. Therefore
      mycotic keratitis should be suspected in every patient with a corneal lesion and
      should be ruled out promptly to save sight and before commencing steroids and
      antibiotics.

PMID- 12785171
TI  - Evaluation of serological tests for the diagnosis of tuberculosis.
AB  - To evaluate the use of antibody detection kits in the diagnosis of pulmonary
      tuberculosis in an endemic area, serum samples from cases (sputum smear positive
      for AFB) and controls (healthy young adults) were collected and tested using five
      different kits. Sensitivity, specificity and predictive values were calculated
      using smear positivity as gold standard. Sensitivity of tests varied from 46% to
      68% and the specificity from 68% to 100%. None of the kits evaluated can be used
      as a single screening test for tuberculosis. However kits with good specificity
      may be used in conjunction with conventional methods for diagnosis.

PMID- 12785172
TI  - Evaluation of antibacterial activity of Mangifera indica on anaerobic dental
      microglora based on in vivo studies.
AB  - The present study was carried out to compare the subgingival plaque microflora in
      mango leaf users. Fifty subjects of both sexes, 25 of them used tooth brush and
      25 used mango leaf as their home care hygiene device were included in the study.
      The microbiological evaluation for specific bacterial counts of Actinobacillus
      actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis,
      Fusobacterium nucleatum and Peptostreptococcus micros were carried out for all
      subject. Specific microbial evaluation revealed significant decrease in the
      proportion of P. intermedia and P. gingivalis in mango leaf users compared to
      tooth brush users. It shows that mangiferin possesses antibacterial activity in
      vivo against specific periodontal pathogens such as P. intermedia and P.
      gingivalis. Use of mango leaf in conjunction with a tooth brush will be a good
      home care device for maintenance of oral hygiene.

PMID- 12785173
TI  - Anti dermatophytic activity of Azardirachta indica (neem) by invitro study.
AB  - The leaf and seed extracts of the Plant Azardirachta indica were tested for
      antidermatophytic activity against dermatophytes such as Trichophyton ruberum,
      Trichophyton, Mentagrophytes, Trichophyton violaceum, Microsporum nanum and
      Epidermophyton floccosum by tube dilution technique. The minimum Inhibitory
      concentration (MIC) of neem seed extract was found to be lower tan that of neem
      leaf when tested against different species of Dermatophytes.

PMID- 12785174
TI  - Human toxocariasis and ascariasis: concomitant parasitism in Srinagar, Kashmir,
      India.
AB  - Human toxocariasis caused by Toxocara canis is common in both developing and
      developed countries and leads to visceral larva migrans with high morbidity and
      mortality. Ascariasis caused by Ascaris lumbricoides, too has global distribution
      and in India, high prevalence rate has been reported in Kashmir (J & K State).
      Both nematode parasites, Toxocara canis and A. lumbricoides require similar
      biological and environmental conditions for the development of eggs in soil.
      Therefore, the present study was attempted to detect the antibody response to T.
      Canis excretory-secretory (ES) antigen by enzyme linked immunosorbent assay in
      patients attending Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar,
      Kashmir to assess the magnitude of human toxocariasis in Kashmir, the highly
      endemic area of ascariasis. Interestingly, it was observed that 38 (82.60%) out
      of 46 patients harbouring Ascaris Iumbricoides had positive antibody response to
      T. Canis ES antigen while none of the 15 normal healthy subjects from the same
      endemic zone, 25 from low endemic zone Chandigarh and 15 from other parasitic
      infections (hookworm, hydatidosis, cysticercosis) indicated detectable positive
      response. Majority of the ascariasis positive patients studied were in the age
      group of 21-40 years. However, one ascariasis patient studied in the age group of
      1-10 years (4 years old) had also positive antibody response to T. Canis antigen.
      This study is the first report of human toxocariasis in Kashmir, India, an
      endemic zone for ascariasis and emphasizes the need for detailed epidemiological
      study for the ultimate prevention and control of this disease

PMID- 12785175
TI  - Profile of transfusion transmissible infections and associated risk factors among
      blood donors of Kerala.
AB  - Blood transfusion is an important mode of transmission of infections to the
      recipient. The aim of the study was to assess the prevalence of transfusion
      transmissible infections and the possible risk factors among blood donors. During
      the study period (1994-99) donor samples were screened for HBsAg, HIV, HCV and
      Syphilis. The relevant donor history was examined to identify the risk factors
      leading to transfusion transmissible infections. The prevalence of infection was
      3.1% among donors, with HBsAg constituting 1.3%, HCV 1.4%, HIV 0.2% and RPR 0.2%.
      In a classification based on occupation, class III donors (drivers, Businessmen &
      men in uniform) showed a significantly higher incidence of transfusion
      transmissible infections for HIV (0.38%) and Syphilis (0.36%). Health care
      workers constituted only a small fraction of the study; prevalence of infections
      was low among them. History of jaundice or hospitalization was not associated
      with higher incidence of seropositivity. Seropositivity for HIV is relatively low
      compared to similar studies conducted in other regions of the country. This
      finding is attributed to the pre donation counseling in donor selection. An
      important outcome of the study is that Class III donors form a high-risk group
      for transfusion transmissible infections.

PMID- 12785176
TI  - Geographical distribution of hepatitis C virus genotypes in India.
AB  - HCV isolates from around the world show substantial nucleotide sequence
      variability throughout the viral genome. Based on the identification of these
      genome differences various genotypes and subtypes have been described from
      different geographical regions. They have been tentatively classified into six
      major genotypes and more than 30 subtypes, but new subtypes are continually being
      discovered. In recent years, substantial evidence has emerged indicating that
      typing and subtyping for HCV is clinically important. The present study aims at
      determining and comparing the prevalence of different genotypes from different
      parts of India (North, South, East and West). A total of 153 samples representing
      different regions have been genotyped in our lab. Our studies document a high
      prevalence of genotype 3 (> 76%) and very low prevalence of genotype 2 (< 2%), as
      a whole. However, genotype 3a has been found to be the highest (50%) with a
      decreased frequency of approximately 25% in the case of 3b, approximately 14% in
      1b and approximately 10% in 1a, whereas a minimal number (approximately 4%) of
      genotype 4 has been found only in Southern and Western India.

PMID- 12785177
TI  - Epithelioid haemangioendothelioma of the liver.
AB  - Epithelioid haemangioendothelioma is a well-recognized vascular neoplasm but can
      be mistaken for metastatic adenocarcinoma or other primary liver tumors. We
      present a case of epithelioid haemangioendothelioma of the liver in a 62 year old
      woman, in whom the diagnosis was missed by various pathologists. This patient
      presented with loss of appetite and weight, and fever. She rapidly deteriorated
      and died presumably of liver cell failure. The characteristic histological
      features and the positive immunostaining for endothelial markers (CD31 & Ulex
      europaeus) confirmed the diagnosis.

PMID- 12785178
TI  - Disseminated histoplasmosis in an AIDS patient diagnosed on bone marrow.
AB  - A 29 year old male drug addict, who was HIV positive presented with fever and
      hepatosplenomegaly. Bone marrow examination revealed Histoplasma capsulatum
      confirmed by PAS & GMS stains. However patient had a rapid downhill course with
      multiorgan failure and died before specific treatment could be instituted.

PMID- 12785179
TI  - Castleman's disease of the retroperitoneum--a case report.
AB  - A rare case of Castleman's disease of retroperitoneum is reported. The patient
      was an operated case of serous papillary carcinoma ovary. She was found to have
      an abdominal mass during follow-up. The mass was considered to be metastatic in
      origin and was resected. Histologically, it was diagnosed as a case of
      Castleman's disease.

PMID- 12785180
TI  - Trichosporonosis due to Trichosporon beigelli in two hospitalized patients.
AB  - Trichosporon beigelli has been reported to cause invasive disease such as blood
      stream infection in severely immunocompromised patients. Two cases of urinary and
      disseminated trichosporonosis by Trichosporon beigelli in hospitalized patients,
      with predisposing factors such as prolonged hospital stay, continuous urinary
      catheterization and broad spectrum antibiotics are reported.

PMID- 12785181
TI  - Nasal cerebral heterotopia: a case report.
AB  - Nasal cerebral heterotopia (nasal glioma) are rare congenital benign masses of
      neurogenic origin with intranasal location, or both. An extranasal case is
      reported in a 2-year-old-boy without any bony defect or connection with brain.
      Histology and immunohistochemistry confirmed the diagnosis.

PMID- 12785182
TI  - Squamous cell carcinoma in situ arising in mature cystic teratoma.
AB  - Mature cystic teratomas of ovary are common tumors. A few may exhibit malignant
      degeneration, most of these being invasive squamous cell carcinoma. We report a
      rare case of pure squamous cell carcinoma in situ in benign cystic teratoma.

PMID- 12785183
TI  - Diagnosis of atypical fibroxanthoma--a case report.
AB  - Atypical fibroxanthoma has a wide spectrum of histological and cytological
      appearances. One recently described variant is atypical fibroxanthoma with touton
      type giant cells. We also came across this case in a 24 year old male student who
      presented with a sub epidermal nodule on the right shoulder for the last one
      year. The lesion was aspirated, it should spindle shaped cells, giant cells, and
      collagen. Giant cells had multiple vacuoles and pink colored granules in their
      cytoplasm. He was diagnosed as atypical fibroxanthoma. The tumor was excised and
      histopathology confirmed the diagnosis. Complete excision was curative.

PMID- 12785184
TI  - Cryptococcal lymphadenitis and meningitis in human immunodeficiency virus
      infection--a case report.
AB  - Cryptococcal meningitis (CM) is the commonest life threatening opportunistic
      fungal disease in Human Immunodeficiency Virus (HIV) infected individuals. But
      there are very little reports of lymphadenopathy along with cryptococcal
      meningitis, although cases of pulmonary, Intestinal, Bone marrow and retinal
      involvement have been described earlier. Here we report a case of cryptococcal
      meningitis associated with generalized lymphadenopathy and hepatosplenomegaly.

PMID- 12785185
TI  - Dedifferentiated chordoma--a case report.
AB  - A case of a recurrent sacro-coccygeal chordoma is reported which histologically
      showed an admixture of a conventional chordoma and a pleomorphic sarcoma. These
      tumours are called dedifferentiated chordomas and carry an ominous prognosis.

PMID- 12785186
TI  - Congenital leukaemia in Down Syndrome--a case report.
AB  - A 17 days old male infant, who had features of Down Syndrome, presented with
      fever, refusal to feed and seizures. He had papular, crusted skin lesions,
      moderate hepatosplenomegaly and a rapid downhill course. Peripheral blood and
      bone marrow aspirate showed features of acute leukaemia. Congenital Leukaemia is
      a rare malignancy associated with a very poor prognosis. Paradoxically, many
      cases of Congenital Leukaemia, especially in infants with Down Syndrome, show
      spontaneous remission.

PMID- 12785187
TI  - Solitary intramuscular nasal Juvenile Xanthogranuloma: a case report with review
      of literature.
AB  - Juvenile Xanthogranuloma is a non-langerhans cell histiocytosis characterized by
      yellowish cutaneous nodules that usually appear in early infancy and childhood.
      Intramuscular variant is a rare form, with only eight reported cases, and none
      reported in ala of nose. Sheets of histiocytes, few touton giant cells and
      infiltrative borders makes it susceptible to misdiagnosis as childhood sarcomas
      or lymphoproliferative disorders. Awareness of the lesion aided by
      immunohistochemistry helps in reaching the proper diagnosis.

PMID- 12785188
TI  - Extradural myxopapillary ependymoma with sacral osteolysis--a case report.
AB  - Extradural ependymomas arising from filum terminale externa in the sacrococcygeal
      region are very rare. Since 1937, out of 58 cases reported in English literature,
      only 13 cases of tumor located presacrally in the retrorectal space, have been
      reported. The authors report a 38 yrs old male with a primary ependymoma of the
      sacrococcygeal region causing extensive sacral destruction.

PMID- 12785189
TI  - Optimal imaging in static telepathology.
AB  - Telepathology is the most recent addition to the diagnostic armory of the
      Pathologist. In spite of its relative limitations, as compared to Dynamic
      Telepathology, Static Telepathology has been widely accepted as a low-cost
      diagnostic and consultation tool, especially in those remote areas where expert
      opinions or second opinions on histopathology, cytopathology or haematopathology
      are not readily available to the reporting pathologist. For an accurate
      Telepathology performance, optimal quality of images is required. Knowledgeable
      use of available hardware and software have made it possible to produce high
      quality images, making Static Telepathology a reliable diagnostic tool.

PMID- 12785190
TI  - Artificial neural network--mechanism and application in pathology.
AB  - Artificial neural network (ANN) is the unique system, which simulates human brain
      in many respects and there is high hope that it may achieve higher mental
      functions. In this brief review we have discussed the basic mechanism of
      artificial neural network along with its application in the field of pathology.

PMID- 12785191
TI  - Pancytopenia--a clinico haematological study of 200 cases.
AB  - The present study was designed to ascertain the percentage of occurrence and
      causes of pancytopenia. All the cases of pancytopenia from July 2001 to June 2002
      (one year) were examined in the Department of haematology, Safdarjung Hospital,
      New Delhi. Bone marrow aspirations/biopsy were performed in most of the cases
      (200 out of 250 cases). The commonest cause of pancytopenia, in our hospital was
      Megaloblastic anaemia (72%), followed by Aplastic anaemia (14%) and others.

PMID- 12785192
TI  - [Regional chemotherapy for pancreatic cancer].

PMID- 12785193
TI  - [Use of biological response modifiers in oncology].

PMID- 12785194
TI  - [Hormonal-metabolic status of cancer patients with late-onset menopause].
AB  - Late-onset of menopause is a marker of risk factor for neoplasia in the
      reproductive system and, conversely, anti-risk for certain non-infectious
      diseases, such as cardio-vascular disease or osteoporosis. We studied 118
      postmenopausal patients with early endometrial and breast cancers. The
      investigation was particularly concerned with hormonal-metabolic status versus
      age at menopause age at. While a Quetelet index/age was irrelevant, blood
      cholesterol and insulin (120 min) concentrations and tumor estrogen/progesterone
      receptor ratios were relatively higher in the late-onset group ((52 yrs). This
      group showed a correlation with age at menopause while the other one--with its
      duration. Insulin/body weight ratios were higher in the late-onset group while
      LH/FSH--lower. Hence, patients of the same age but differing in age at menopause
      age at may show differences in hormonal-metabolic status as well. This feature
      may be significant in identifying both biological distinctions of associated
      tumors and their clinical course.

PMID- 12785195
TI  - [Detection of herpesvirus markers in patients with precancerous lesions of the
      lungs and stomach].
AB  - Blood-serum concentrations of antibodies to such viruses as herpes simplex virus,
      cytomegalovirus and Epstein--Barr virus have been assayed versus frequency of
      viral DNA detection in blood and saliva suspensions from patients with lung and
      stomach pre-cancers. Condition of local immunity of oral mucosa was assessed on
      the basis of saliva levels of secretory IgA and lysozyme. It was found that as
      local immunity of oral mucosa deteriorated, irrespective of pre-cancer
      localization, high titers of antiviral antibodies (class G) were established. The
      frequency of herpes DNA was much higher in lymphocytes and cellular sediment from
      saliva of patients with gastric pre-cancers. The role of herpes viruses in the
      pathogenesis of precancerous diseases and malignances is discussed.

PMID- 12785196
TI  - [Autopsy-based data on radionuclide concentrations in selected endocrine organs
      (Vitebsk region, Belarus)].
AB  - Gamma spectometry was used to compare 137Cs levels in certain endocrine organs of
      victims of general and oncological diseases of different localizations. The
      radionuclide distribution in the thyroid, adrenals and pancreas was studied.
      Elevated concentrations were found in the endocrine system of cancer patients.

PMID- 12785197
TI  - [Effect of chemotherapy on cytosol proteins of ovarian tumors].
AB  - Cytosol proteins of malignant ovarian tumors were studied with one- and two
      dimensional gel electrophoresis, prior to and after effective chemotherapy with
      cisplatin and taxotere. Effective chemotherapy caused the bands and spots of 29,
      36 and 50-55 kDa to fade significantly or disappear completely. It is suggested
      that protein 36 kDa is the proliferating nuclear cell antigen while one of the
      proteins 50-55 kDa--betatubulin. These proteins may serve as additional markers
      of ovarian tumor sensitivity to chemotherapy.

PMID- 12785198
TI  - [Urokinase and tissue type plasminogen activators and their type-1 inhibitor (PAI
      1) in gastric cancer].
AB  - The levels of urokinase (uPA) and tissue type (tPA) plasminogen activators and
      their type 1 inhibitor (PAI-1) were determined by immunoassay in tumor cytosols
      and samples of histologically unaltered adjacent mucosa in gastric cancer
      patients. Gastric tumor revealed enhanced uPA and PAI-1 matched by decreased tPA
      in intact mucosa. The expression of uPA and PAI-1 was particularly was high at
      the later stages of the disease. The concentrations of uPA in tumor tissue
      increased with age. No significant correlation was established between levels of
      plasminogen activation system components, on the one hand, and histopathological
      grading of tumor, on the other.

PMID- 12785200
TI  - [Improvement of the logistical organization of ambulatory care for cancer
      patients].
AB  - Development and successful use of new logistical know-how provide means of
      improving the standards of oncological service. It is a particularly urgent
      problem at the grass roots level, yet it has not been appreciated to the full. A
      possible solution may be deployment of outpatient oncological departments within
      the framework of polyclinics which will en sure that the available diagnostic and
      therapeutic facilities are used more effectively. Such an arrangement will
      provide expertise and logistics standards inaccessible for a consulting
      oncologist. According to a five-year survey of the performance of an outpatient
      oncological department at a municipal polyclinic in a Mid-Urals town, more cancer
      patients have been given better medical service due to use of earlier and faster
      diagnostic procedures.

PMID- 12785199
TI  - [Antigen-specific immunotherapy as a component of combined therapy for malignant
      brain tumors].
AB  - The purpose of the present research was to study immunity in the course of
      complex treatment for malignant gliomas of the brain and to evaluate
      extracorporeal antigen-specific immunotherapy (EASIT), a pilot procedure which
      was carried out according to an approved protocol. Initially, lowered HLA-DR+
      monocyte count and in vitro inhibition of proliferative activity were reported in
      all patients. Inductive EASIT started in early postoperative period aborted
      immune disturbances caused by surgery. In 1998-2000, the procedure was performed
      in 33 patients with anaplastic astrocytoma (AA) (20) and glioblastoma (GB) (13).
      Mean dose of cell infusion was 2.43(0.18 x 109/patient and was well tolerated.
      There are 22 survivors and 9 patients died (GB--4 and AA--5; overall mortality-
      29%). Mean relapse-free survival was 14.2 mo (22); stable remission during 12-18
      mo--37.5% (3/8)(GB) and 64% (9/14) (AA) Complete rehabilitation of immunity was
      generally reported 12 mo after the course of EASIT. Hence, complex treatment
      (surgery + EASIT) enhanced its efficacy in the management of brain tumors.

PMID- 12785201
TI  - [Cancer morbidity in the Republic of Northern Ossetia-Alania (1991-2000)].
AB  - The cancer morbidity in the Republic of North Ossetia-Alania is still high: 248.2
      (1998), 243.1 (1999) and 241.3 (2000) per 100,000. The site distribution patterns
      varied significantly: the leading localizations in 1991 were trachea, lungs and
      bronchus--32.1; breast--28.3; skin--26.5; stomach--21.2 and hemopoietic organs-
      18.0. By the year 2000, the situation had changed dramatically: breast--60.2;
      skin--33.7 and respiratory system--20.4.

PMID- 12785202
TI  - [Ten-year experience with the use of laser in surgical endoscopy in cancer
      patients].
AB  - The calculation data are presented on a critical temperature area (45-60 deg. C)
      located in the wall of the gastrointestinal tract, following exposure to
      continuous laser radiation (1.06(m). Positive clinical results were reported on
      the use of the fiber-type modification of the continuous 250W YAG:ND laser in the
      treatment of 217 patients with benign, malignant tumors and cicatricial
      strictures in the lumen of the gastrointestinal tract, trachea or bronchus.

PMID- 12785203
TI  - [The effectiveness of interferon-alpha therapy in Ph-positive chronic myeloid
      leukemia].
AB  - Chronic myeloid leukemia (CML) is a hemopoietic condition caused by chromosomal
      translocation t(9;22)(q34;q11) or bcr-abl fusion gene. The predominant variants
      of bcr-abl oncogene rearrangement are b3a2 and b2a2. The present study evaluated
      the efficacy of interferon-a therapy of CML patients and molecular prognostic
      factors. Cytogenetic response and complete hematological remission were more
      frequent in CML b3a2 treatment with interferon-a. Moreover, after therapy,
      chronic phase lasted in that group (p = 0.026) much longer. Overall survival in
      the group was significantly longer, too (p = 0.046).

PMID- 12785204
TI  - [Experience with xeloda (capecitabine) as a component of chemotherapy for
      relapsing cisplatin-resistant ovarian tumors].
AB  - The effectiveness and tolerability of xeloda (capecitabine), a tumor-reactivated
      oral fluoropyrimidine, alone were investigated in 19 patients, aged 39-79, with
      relapsing and cisplatin-resistant ovarian tumors. Unfavorable prognosis of
      chemotherapy was in 11 cases (57.8%): cisplatin-resistant tumors (7) and early
      relapse--before month 6 (4). Xeloda was administered orally, 1,250 mg/m2, twice a
      day, for two weeks at an interval of one week. A total of 68 cycles (an average
      of 3.6 cycles) were evaluated. Complete response was registered in 1, partial--4,
      and stabilization--4 cases. Total response was in 26.3%, clinically significant
      effect--47.3% (9 out of 19). Toxic side-effects generally persisted with in stage
      I-II (palm-and-sole syndrome, leukopenia, neutropenia, sickness, vomiting,
      diarrhea) without interfering with the treatment.

PMID- 12785205
TI  - [Risk of endometrial hyperplasia and carcinoma in breast cancer patients
      receiving adjuvant tamoxifen].
AB  - The antiestrogen drug tamoxifen, which is widely used in adjuvant hormone therapy
      of breast cancer, presents certain risk of causing hyperplasia and endometrial
      carcinoma. Our clinical data on 1,969 breast cancer patients (stage I-III)
      (tamoxifen--947; control--1,022) showed a double rise in endometrial carcinoma
      risk in cases receiving hormone therapy. Endometrial carcinoma incidence in
      tamoxifen-treated patients was 3% while in the untreated ones--1.6% (p < 0.05).
      According to the endometrial tissue study in 439 breast cancer patients,
      proliferative effect of tamoxifen in the form of endometrial hyperplasia was 5--6
      times in tamoxifen users. Meanwhile, endometrial carcinoma and hyperplasia risk
      increased during a much longer exposure to tamoxifen and in combination with such
      factors as obesity, diabetes mellitus, uterine myoma and estrogen-type
      colpocytological response. Hence, breast cancer patients need to undergo dynamic
      follow-up of the endometrium including ultrasonic examination of the small-pelvis
      organs and cytological study of ecto- and endocervical smears and endometrial
      aspirates.

PMID- 12785206
TI  - [Clinical effectiveness of nadroparin calcium in the surgical treatment of breast
      cancer].
AB  - The report deals with an assessment of frequency of fatal thromboembolic
      complications after surgery for breast cancer, in particular, frequency and
      severity of the side-effects of calcium nadroparin treatment as a component of
      surgical preparation. Considering the low incidence of thromboembolic
      complications in such patients and the side-effects of anti-coagulant therapy, it
      is suggested that decisions be made on a strictly individual basis under
      stringent clinical control.

PMID- 12785207
TI  - [Stomach cancer metastasizing to the para-aortic lymph nodes: possibilities of
      surgical treatment].

PMID- 12785208
TI  - [Potential of abdominal computed tomography and ultrasonography for the complex
      diagnosis of early gastric cancer].
AB  - The potential of computed tomography and ultrasonography in making complex
      diagnosis of "small forms" of early gastric cancer was demonstrated by evaluation
      of the data on examination of 116 patients and the pivotal role of the extent of
      intramural invasion was established. The semiotics of computed tomography and
      ultrasonography for intramural invasion and the sequence of X-ray and endoscopic
      procedures were developed.

PMID- 12785209
TI  - [Experience with tantum rosa treatment for the prevention and management of
      radiation-induced proctitis and vaginitis in uterine and vaginal cancer].
AB  - The investigation has been concerned with the efficacy of Tantum Rosa (Angelini
      Francesco, Italy) in the prevention (21) and therapy (87) of early- and late
      onset radiation injuries of the rectum and vagina in patients exposed to
      radiation for cervical, uterine or vaginal carcinoma. Rectal tenesmus and pain
      subsided following 3-4 administrations at early stages of radiation rectitis.
      Intestinal discomfort was avoided when Tantum Rosa was used for prophylaxis.
      Therapeutic effect was reported after 7-10 administrations for moderate radiation
      vaginitis. Therapy for pannicular epithelite lasted less than two weeks.

PMID- 12785210
TI  - [Magnetic resonance tomography in the staging of uterine neoplasms].
AB  - Diagnostic significance of MR imaging used for cervical carcinoma staging was
      established during the examination of 71 patients with verified tumors stage I
      III. These findings were compared with the clinical and surgical data. MRI
      procedure proved highly effective in detecting uterine body involvement,
      identification of hydroureter caused by the ureters being squeezed by parametrial
      infiltrates as well as reliable exclusion of parametrial infiltration of bladder
      wall invasion. It is instrumental in assessing involvement of tissues around the
      uterus and regional lymph node condition.

PMID- 12785211
TI  - [Doppler ultrasonography in assessing the effectiveness of preoperative
      radiochemotherapy in patients with uterine cervix neoplasms].

PMID- 12785212
TI  - [Combined therapy for patients with invasive bladder cancer].
AB  - Organ preservation has been investigated inmuscle-invasivebladder cancer over the
      past years as an alternative to standard radical cystectomy. However, the
      morbidity of radical cystectomy and early reports of good results of radical
      transuretheral resection of bladder tumors (TURBT) have stimulated interest in
      combined treatment for muscle-invasive bladder cancer. Organ preservation
      requires a trimodal schedule, including transuretheral surgery, mega voltage
      radical external beam radiotherapy (EBRT) and adjuvant chemotherapy (ACT). Our
      results point to the effectiveness of combined therapy of urinary bladder in old
      patients with invasive, advanced cancer (stage T2). These results demonstrate the
      effectness of intra-arterial ACT when used in combination with EBRT.

PMID- 12785213
TI  - [Etiology and pathogenesis of diffuse and intestinal forms of gastric cancer].

PMID- 12785214
TI  - [Mikhail Pavlovich Ptokhov (100th anniversary of birth)].

PMID- 12785215
TI  - [Current issues in gastroenterology in our country].

PMID- 12785216
TI  - [Transplantation of isolated hepatocytes in hepatic failure].
AB  - The authors review achievements in the field of prophylaxis and treatment of
      acute liver failure with donor's allo- and xenogenic isolated hepatocytes.
      Present-day clinical and experimental data on transplantation of hepatocytes
      evidence for their ability to produce a detoxicating action, to restore the lost
      functions of the affected part of the liver, to prevent death of hepatocytes
      caused by ischemia, to activate regeneration. This method is easy to conduct and
      obtained cells from one donor can by used for many recepients. Problems in
      transplantation of isolated hepatocytes are shown. Factors stimulating hepatocyte
      regeneration are mentioned with a special focus on hepatocyte growth factor
      having the most potent mitogenic effect.

PMID- 12785217
TI  - [Long-term outcomes of viral myopericarditis in young patients].
AB  - Long-term follow-up (mean 14.1 +/- 6.6 years) of 54 young patients who have
      undergone acute viral myopericarditis of mild or moderate severity demonstrates a
      favourable outcomes in the majority of the examinees in spite of residual fibrous
      changes in the myocardium registered at ECG. Fibrous pericardial thickening
      detected in 89.4% patients at echocardiography is proposed as a differential
      diagnostic indicator of old myopericarditis.

PMID- 12785218
TI  - [Biofeedback-wave rehabilitation therapy in combined treatment of patients with
      stable angina pectoris].
AB  - 160 patients with stable stress angina pectoris (SSAP) received combined
      treatment. One of the modalities was information-wave impact generated by devices
      Azor-IR, Chrono-DMW (microwaves), Chrono-EHF. The impact from Azor-IR proved most
      effective as it reduced the amount of medication without loss of therapeutic
      activity.

PMID- 12785219
TI  - [Effects of diazepam on intracardiac hemodynamics in patients with chronic
      cardiac failure].
AB  - Diazepam effects on intracardiac hemodynamics were studied in 45 patients with
      ischemic heart disease. The patients were divided into 3 groups: a control group
      (n = 13), a group with a systolic dysfunction (EF < 45%, n = 16) and a group with
      a diastolic dysfunction (E/A < 1.0, n = 16). Echocardiography was made before and
      after intravenous injection of 10 mg diazepam (relanium, "Polfa). The above
      diazepam injection improved heart rate and diastolic blood pressure in patients
      with left ventricular systolic dysfunction, cardiac pump function improved in
      patients with initial diastolic or systolic dysfunction. In the controls these
      parameters worsened. Diastolic function was not influenced much in all the three
      groups. Thus, combination of a sedative effect, a moderate positive action on
      cardiac pump function and no negative impact on diastolic filling characterizes
      diazepam as a stress-limiting medicine in patients with chronic cardiac failure.

PMID- 12785220
TI  - [Non-pharmacological correction of impaired platelet hemostasis in hypertensive
      patients with metabolic syndrome].
AB  - Low-calorie diet and individually adjusted physical exercise used in combination
      in hypertensive patients with metabolic syndrome correct shifts in blood lipid
      spectrum, relieve peroxidation syndrome, normalize impaired platelet hemostasis,
      suppress enhanced adhesive and aggregation functions of platelets in vitro and
      their intravascular activity. The improvement reached maximum after 24 weeks of
      treatment but control values were not achieved. Therefore, for effective
      correction of metabolic processes and platelet hemostasis in hypertensive
      patients with disorder of glucose tolerance, non-pharmacological measures should
      be supplemented with pharmacological ones.

PMID- 12785221
TI  - [Risk of recurrent cerebral embolism in isolated and combined cardial pathology
      in patients with cardio-embolic stroke].
AB  - To study cerebral microembolism and focal impairment of the brain in patients
      with isolated and combined cardiac affection, we examined 84 patients who had
      survived cardioembolic stroke (CES). The examination included computed tomography
      of the head, echocardiography and transcranialdopplerographic monitoring of
      microembolic signals (MES). Group 1 consisted of 53 (63.1%) patients with one
      source of cardiocerebral embolism, group 2-31 (36.9%) patients with two potential
      causes of cardial embolic complications. In group 2 average number of documented
      MES (3[1;5]) and average number of cerebral ischemic foci (2[1;2]) were greater
      than those of group 1-2[1;4] and 1[1;1], respectively. As to the size of the
      lesion, it was found that small, middle-size and large foci were also visualized
      in group 2 more frequently. Thus, combination of two sources of cerebral embolism
      observed in 1/3 of CES enhances cardiogenic embologenic potential and probability
      of microembolism transformation into cerebral focal lesion as a result of
      potentiation of different ways of thrombogenesis.

PMID- 12785222
TI  - [Glucocorticoid adrenal function and clinical implications of hydrocortisone
      metabolism tests in patients with bronchial asthma].
AB  - A glucocorticoid adrenal function was studied in 42 perimenopausal women with
      bronchial asthma (BA) by radioimmunoassay estimation of blood hydrocortisone
      levels, free and conjugated fractions of urinary hydrocortisole, 24-h excretion
      of overall 17-OCS and hydrocortisone metabolism index. Replacement estrogens
      inhibit processes of microsomal hydroxylation and reduce clearance of the
      introduced steroids. Replacement therapy with sex hormones conducted to correct
      menopause had no negative influence on hydrocortisone blood levels and its
      metabolism.

PMID- 12785223
TI  - [Soluble receptors of TNF-alpha with molecular mass 55 kDa in rheumatoid
      arthritis: clinical role].
AB  - To evaluate clinical implications of the serum level of soluable receptors of
      tumor necrosis factor alpha (TNFa) with molecular mass 55 kDa (rTNF-55R) in
      rheumatoid arthritis, serum levels of rTNF-55R and rTNF-75R were measured with
      the use of radioimmunoassay in 76 RA patients, 38 donors and in 25 RA patients,
      10 donors, respectively. RESULTS: Elevated serum level of rTNF-55R was recorded
      in 55.3% RA patients. This level correlated with basic clinical and laboratory
      parameters of RA, the disease activity, values of DAS indices. It is concluded
      that a serum level of rTNF-55R adequately reflects clinico-laboratory activity of
      RA and its measurement can be used for assessment of RA activity and treatment
      efficiency.

PMID- 12785224
TI  - [Signs of reactive arthritis in large joint osteoporosis].

PMID- 12785225
TI  - [Clinical picture, diagnosis and treatment of chronic opisthorchiasis].
AB  - The data on 750 patients with opisthorchiasis aged 16 to 69 years (437 males and
      313 females) suggest the conclusion that chronic opisthorchiasis is a systemic
      disease of man caused by trematoda Opistorchis felimus which parasitizes in the
      hepatic ducts, gallbladder, pancreas. This parasite provokes allergic, mechanical
      and neurogenic reactions in the host. Targeted diagnosis should be initiated in
      existence of the characteristic symptom triad: conjunctival changes (Paltsev's
      symptom), tremor of the tongue, fissures of the tongue. Chronic opisthorchiasis
      is treated in three stages: preparation measures, specific chemotherapy,
      rehabilitation.

PMID- 12785226
TI  - [Amlodipin in the treatment of cardiovascular diseases].

PMID- 12785227
TI  - [Safety of paracetamol as a representative of nonprescription analgetics
      antipyretics].
AB  - Paracetamol is a well-known analgetic-antipiretic drug widely used in medical
      practice. In therapeutic doses (4 g/day for adults and 60 mg/kg/day for children)
      paracetamol relieves fever and non-severe pain with minimal risk of complications
      both in adults and children. But medical professionals should know that in
      extremely high doses (above 10 g for adults) paracetamol has a hepatotoxic
      effect. Overdose intake of paracetamol in Russia happens rarely, it occurs by
      chance or in attempted suicide. In such a case the antidote must be used to
      protect the liver. This antidote for paracetamol is N-acetylcysteine.

PMID- 12785228
TI  - [Right ventricular myocardial infarction in a patient with infectious
      endocarditis].
AB  - A case of right and left ventricular myocardial infarction in infectious
      endocarditis of the aortic valve in an injected drug abuser is reported. The
      infarction was diagnosed only in autopsy. Diagnostic difficulties are discussed.
      The literature on the problem is listed.

PMID- 12785230
TI  - [Connective tissue dysplasia syndrome in cardiological practice].
AB  - Ehlers-Danlos syndrome was diagnosed in an elderly patient who had been long
      observed as a patient with ischemic heart disease, then dilated cardiomyopathy.
      Ehlers-Danlos is a rare type of connective tissue dysplasia syndrome.

PMID- 12785229
TI  - [Post-tuberculous fibrous mediastinitis: a report of a case followed-up for many
      years].
AB  - The paper reports a rare case of fibrosing mediastinitis of posttuberculous
      genesis caused by infection with Mycobacterium bovis. Such cases are not
      available in the literature so far. The patient was observed from 1956 to 2001.
      Bovine tubercle bacilla affect mediastinal lymph nodes which undergo fibrosis
      resulting in stenosis of the trachea, major bronchi, esophagus. Narrowing of the
      chest duct leads to formation of severe recurrent transudate in the left pleural
      cavity (for 3 years 70 pleural punctures were made with removal of a total of 22
      l of fluid).

PMID- 12785231
TI  - [Tuberculosis of the gallbladder: clinico-ultrasonographic diagnosis].

PMID- 12785232
TI  - [Therapeutic possibilities for the inhibition of the renin-angiotensin
      aldosterone system].
AB  - The dysfunction of the renin-angiotensin-aldosterone system and its inhibition is
      a powerful therapeutic tool in the treatment of cardiovascular diseases. This
      system is a very ancient and sensitive mechanism, which reacts very much to the
      impacts from the environment. The system can be inhibited through four different
      ways; in the practice ACE inhibitors and ARBs are used mostly. Other--also
      beneficial--drugs might cause the over stimulation of the system. The inhibition
      of the RAAS system have significant impact on reduction in cardiovascular
      morbidity and mortality and have been shown convincingly additional benefits
      comparing to other treatments.

PMID- 12785234
TI  - [Inhibition of the renin-angiotensin system to prevent target organ damage: the
      "renal continuum"].
AB  - Similar to the atherosclerotic cardiovascular disease, primary and secondary
      renal diseases are also characterised by a "continuum". The "renal continuum"
      comprises the initial immunologic, metabolic or hemodynamic insult which, through
      progressive glomerular and interstitial renal damage, results in end stage renal
      failure. The rennin-angiotensin system plays a pivotal role in the progression of
      renal disease. We use diabetic nephropathy to demonstrate the clinical benefits
      that can be attained by administering inhibitors of the rennin-angiotensin system
      in more and more progressive stages of the diabetic "renal continuum". Evidence
      from clinical trials among diabetic patients attest to the notion that specific
      inhibition of the rennin-angiotensin system provides a benefit that is above what
      could be expected from the blood pressure lowering effects of these drugs alone.

PMID- 12785233
TI  - [Diurnal blood pressure control in the optimal treatment of hypertension].
AB  - Mean 24-hour blood pressure values of ambulatory blood pressure monitoring (ABPM)
      are more closely related with target organ damage and cardiovascular events in
      hypertension, than clinic measurements. Both daytime and nighttime blood pressure
      and short-term blood pressure variability associated with these intermediate and
      hard cardiovascular outcomes abd should be controlled with antihypertensive
      treatment. A large increase in blood pressure variability may also occur in the
      early morning and with some antihypertensive drugs, without a consistent and
      smooth, more than 24-hour effect. For example, unlike some other angiotensin
      receptor blockers, telmisartan provides consistent blood pressure reduction for
      24-hour, including the critical early morning period.

PMID- 12785235
TI  - [Effects of angiotensin receptor inhibitors on cardiovascular endpoints--current
      and future evidence].
AB  - There is close relationship between hypertension, organ damage and cardiovascular
      mortality. The control of hypertension or the regression of organ abnormalities
      can cause reduction in mortality but this is to be proven by each drug. Similar
      degree of antihypertensive effect with different type og drugs can result in
      different amount of regression of left ventricular hypertrophy. Telmisartan can
      cause reduction of LVH even in small, non-hypotensive doses. Combination of ACE
      inhibitors and ARB has a lot of theoretical advantage, the available clinical
      data are positive however some conflicting data are to be clarified yet. The
      ongoing ONTARGET study will give answers to a lot of this questions in 4 years.

PMID- 12785236
TI  - [Applications of the botulinum A toxin].
AB  - The botulinum A toxin inhibits the release of acethylcoline from the vesicles of
      presynaptic neuronal end plates. Its effect is a transient pharmacological
      neurectomy. The toxin is used more and more widespreadingly. It selectively
      inhibits certain muscles or groups of muscles. Its use is of outstanding
      importance in the treatment of blepharospasm, a disease possibly causing
      transient functional blindness. This blindness develops randomly, with
      undetermined duration, therefore it may even threaten the life of the patient.
      There is no alternative treatment. In ophthalmology, the toxin is used in the
      therapy of strabismus and nystagmus, as well as replacing entropion operations.
      Most often its use is suggested in the treatment of focal dystonies, dysphonia,
      tremor palatinus, dysphagia, spasm of the oesophagus sphincter muscle, nasal
      hypersecretion, hemifacial spasm, headaches, focal hyperhydrosis, proctalgia
      fugax, diabetic gastroparesis and difficulties in urination. In the past few
      years, the toxin has been used for esthetic reasons as well. By relaxing the
      muscles causing wrinkles, non-permanent result may be reached with its use. The
      botulinum A toxin does not have general side effects. As local side effects,
      haematomas and unwanted, transient paresis of the neighboring muscles can be
      mentioned.

PMID- 12785237
TI  - [Combined treatment of acute ischemic syndrome].
AB  - Lots of changes has been made on the treatment of ischaemic heart disease
      (especially the acute ischaemic syndrome) during the last few years. Large scale,
      multicentre trials provided clinical evidences the novel therapeutical approach
      of acute coronary syndrome (ACS). In order to suit this great challenge and to
      treat the patients with ACS successfully, all efforts should be addressed to open
      the occluded coronary artery, and to restore coronary circulation as soon as
      possible. During this process the first mandatory step is to perform acute
      coronarography, in order to reveal the exact pathomorphology, and to make a plan
      for the optimal treatment. Patients with acute ischaemic syndrome should be
      transferred to the haemodynamic laboratory within 2-6 hours from the development
      of the first clinical symptoms, to perform a primary coronary intervention and/or
      pharmacological treatment when required. A well-established, local/regional
      system is suitable to organize different levels of medical treatment from the
      family medicine to the regional heart center, and enables to transfer patients to
      the appropriate place without delay, and gives an equal chance for every patient
      with acute ischaemic syndrome.

PMID- 12785238
TI  - [Treatment of bronchial asthma in pregnancy].
AB  - The prevalence of bronchial asthma, similarly to the normal population, is also
      increasing among pregnant women. Asthma a chronic inflammatory disease of the
      airways, is one of the most common medical problems that can complicate
      pregnancy. The cornerstone of asthma management in pregnancy is to implement such
      treatment strategies that can maintain normal maternal pulmonary function and
      prevent fetal complications. The aim of the present article is to summarize the
      recent publications and guidelines on the safety and efficacy issues of asthma
      treatment during pregnancy.

PMID- 12785239
TI  - [Activation of the nuclear factor kappa B--key role in oncogenesis? Chronic
      hepatitis C virus infection and lymphomagenesis].
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection may have an etiopathogenic role
      in development of B-cell non-Hodgkin lymphoma (NHL). Antiapoptotic effect of the
      HCV may display via activation of nuclear factor kappa B (NF-kappa B)
      transcription factor and can lead to development of carcinoma. AIMS: 1. Activated
      NF-kappa B was examined in peripheral blood lymphocytes of patients with HCV
      infection or NHL, and HCV positive B-cell NHL. 2. NF-kappa B was detected in
      liver biopsies of patients with HCV positive hepatocellular carcinoma (HCC) and
      in lymphnodes of patients with HCV positive NHL. PATIENTS AND METHODS: 1. Fifteen
      patients with chronic HCV infection, 13 patients with B-cell NHL (among them 4
      HCV positive) and 10 healthy subjects were examined for the activity of NF-kappa
      B using electrophoretic mobility shift assay (EMSA). 2. Immunohistochemistry was
      performed in 8 liver biopsies from HCV positive patients and 2 HCC patients (1
      HCV positive and 1 HCV negative) and 2 B-cell NHL patients (1 HCV positive and 1
      HCV negative). RESULTS: 1. In the HCV negative control samples there was no shift
      detected, but we found NF-kappa B specific oligonucleotide-protein complexes in
      the lymphocyte extracts from all HCV positive patients and 10/13 (76.92%) in B
      cell NHL. 2. NF-kappa B was detectable in 7/8 cases in liver biopsies from HCV
      positive patients. Strong reaction was detected in nuclei in HCV positive HCC and
      NHL patients (no reaction in HCV negative biopsies). CONCLUSIONS: NF-kappa B
      activation was justified in both diseases, which can connect the development of
      both HCV infection and B-cell NHL. This factor activation may have role in hepato
      and lymphomagenesis.

PMID- 12785240
TI  - [Evidence-based laboratory medicine].
AB  - Patients and society expect physicians to base their approach to any type of
      clinical problem on informed diagnostic reasoning. Informed diagnostics means
      that clinicians understand and readily apply the principles of diagnostic
      decision making, which include an estimate of the pre-test probability
      (prevalence) of diseases and information about the characteristics and
      discriminatory power of the applied investigations. Despite the crucial
      importance of the appropriate use of diagnostic tools in clinical decision
      making, many diagnostic tests have not been subjected to rigorous evaluation to
      establish the diagnostic accuracy and clinical utility of laboratory
      investigations using modern standards of clinical epidemiology. The lack of good
      quality research in the field not only contributes to inappropriate utilization
      of laboratory services but also to wasting significant resources. Evidence-based
      laboratory medicine tries to combat this problem by combining methods from
      epidemiology, biostatistics, clinical and social sciences with basic sciences to
      evaluate the role of investigations in clinical decision making and outcomes for
      patients. Evidence-based laboratory medicine aims to advance clinical diagnosis
      and management of diseases through systematic researching and disseminating
      generalisable new knowledge which meets the standards of critical review on
      clinically effective practice of laboratory investigations. The main phases of
      practicing evidence-based laboratory medicine are 1. question formulation, 2.
      systematic literature search, 3. critical appraisal of literature, 4.
      implementation of evidence into practice, and 5. evaluation of impact in a
      clinical audit cycle. The use of evidence in laboratory medicine requires
      systematically compiled databases of standardised and critically appraised
      information on the test characteristics and diagnostic accuracy of laboratory
      investigations. Such an approach is the Bayes Library that provides information
      on the global and specific measures of test performance in different patient
      groups and settings, in addition to prevalence data of common diseases. The Bayes
      Library will support informed diagnostic decisions and improve patient outcome by
      integrating evidence-based medicine into the diagnostic service, education and
      training of laboratories. The process of constant questioning and reviewing the
      evidence for rational diagnosis of diseases provides a practical tool to identify
      gaps in our knowledge and thus it generates new research ideas in laboratory
      medicine.

PMID- 12785241
TI  - New wine in old bottles: the WHO ICF as an explanatory model of human behaviour.
AB  - The World Health Organization's International Classification of Functioning (WHO
      ICF) is a good but incomplete framework for describing the situation of someone
      with long-term ill health. Several deficiencies exist for which improvements are
      suggested. The WHO needs to integrate the ICF with the ICD-10 to form a
      comprehensive system of classification of illness. Words are needed for normality
      at the level of organ and person, and the words 'histology' and 'physiology', and
      'anatomy' and 'capacity' are suggested for the two levels respectively. A fourth
      context, that of time, is needed to understand fully a person's situation. The
      classification framework needs to take more account of the patient. It needs to
      recognize two separate perspectives, that of the subject and that of external
      observers and it needs to recognize two other specific person-centred phenomena:
      free will and quality of life. With changes and additions to take account of
      these deficiencies, the WHO ICF can be used as a powerful analytic and
      explanatory model of human experience and behaviour in any situation, not only in
      illness and disease.

PMID- 12785242
TI  - A randomized controlled trial of the effects of intensive sit-to-stand training
      after recent traumatic brain injury on sit-to-stand performance.
AB  - OBJECTIVE: To examine the effectiveness of intensive practice of sit-to-stand on
      motor performance, exercise capacity and exercise efficiency in traumatic brain
      injured patients during early inpatient rehabilitation. DESIGN: Single-blind
      randomized controlled pilot study. SETTING: Brain injury rehabilitation unit.
      SUBJECTS: Twenty-four subjects who had recently sustained a severe traumatic
      brain injury (TBI) were randomized into an experimental (n = 13) and a control (n
      = 11) group. INTERVENTIONS: In addition to their usual rehabilitation programme,
      subjects in the experimental group participated in four weeks of intensive
      training of sit-to-stand and step-up exercises with the aim of improving
      performance of sit-to-stand. The control group did no additional sit-to-stand or
      step-up training. MAIN OUTCOME MEASURES: Total number of sit-to-stands in 3 min
      as a measure of motor performance; peak oxygen consumption during a maximal 3-min
      sit-to-stand test (Vo2peak) as a measure of exercise capacity; oxygen consumption
      during a 3-min equivalent workload sit-to-stand test (Vo2equiv) as a measure of
      exercise efficiency. Pre- and post-training measurements were made. RESULTS: The
      exercise programme resulted in a 62% improvement in motor performance (number of
      repetitions of sit-to-stand in 3 min) for the experimental group compared with
      the control group's 18% improvement (p < 0.05). There was no significant
      difference between groups for changes in exercise capacity or efficiency. In the
      experimental group, the increase in Vo2peak from pre-test to post-test correlated
      with the increase in sit-to-stand repetitions (p < 0.05). CONCLUSIONS: Intensive
      task-specific training is recommended as an important component of rehabilitation
      early following severe traumatic brain injury.

PMID- 12785243
TI  - Auditory cues can modify the gait of persons with early-stage Parkinson's
      disease: a method for enhancing parkinsonian walking performance?
AB  - OBJECTIVE: To investigate whether systematically adjusting the rate of auditory
      cues induces corresponding modulations of the temporal and spatial parameters of
      gait of patients with early-stage Parkinson's disease. DESIGN: Subjects performed
      a series of 15 9-metre walks along a level floor under uncued and four cued
      conditions; the order of cued conditions was randomized. SETTING: A physiotherapy
      gymnasium, Manchester, UK. SUBJECTS: Eleven subjects with early-stage idiopathic
      Parkinson's disease. INTERVENTIONS: Preferred pace was established from the
      initial three uncued walks. The rate of auditory cues delivered throughout
      subsequent walks was systematically adjusted for each subject, representing 85,
      92.5, 107.5 and 115% of their mean cadence at preferred walking pace. MAIN
      OUTCOME MEASURES: Mean cadence, mean stride length and mean velocity. RESULTS:
      Repeated measures ANOVA indicated that the mean velocity and mean cadence of
      subjects' gait significantly (p < or = 0.01) increased relative to baseline
      values at cue rates of 115 and 107.5% of cadence at preferred pace and decreased
      at cue rate of 85%. Mean stride length was unaffected by variations in cue rate.
      CONCLUSION: The rate of auditory cues, within the range tested, can modulate
      cadence and thus velocity of gait of subjects with early-stage Parkinson's
      disease. The provision of auditory cues provides a potential strategy for
      enhancing walking performance in these patients.

PMID- 12785244
TI  - Effects of an ankle-foot orthosis on spatiotemporal parameters and energy cost of
      hemiparetic gait.
AB  - OBJECTIVE: To assess the effect of an ankle-foot orthosis on the gait and energy
      parameters of walking in chronic hemiparetic subjects. DESIGN: With/without group
      comparison. SETTING: Consecutive patients recruited from the gait analysis
      laboratory of our rehabilitation department. SUBJECTS: A group of nine chronic
      hemiparetic patients, with the same gait pattern alteration, were evaluated
      during walking at free speed with and without the use of an orthosis. OUTCOME
      MEASURES: Gait analysis and study of energy cost. RESULTS AND CONCLUSION: The
      orthosis significantly improved self-selected speed (15.47 versus 21.39 m/min),
      stride cycle (2.33 versus 2.08 s), stance (1.83 versus 1.48 s) and double support
      (1.55 versus 1.16 s) and reduced energy cost (0.76 versus 0.49 ml O2/kg/m) of
      walking without affecting cardiorespiratory response. Moreover, a significant
      correlation was found between the improvement of double support and the reduction
      of energy cost.

PMID- 12785245
TI  - The influence of illness duration and level of consciousness on the treatment
      effect and complication rate of serial casting in patients with severe cerebral
      spasticity.
AB  - OBJECTIVE: To compare the improvement and complication rates for serial casting
      in patients with shorter as opposed to longer illness duration, and in patients
      with lower as opposed to higher levels of consciousness. DESIGN: A retrospective
      case-comparison study. SETTING: A rehabilitation centre for adult persons with
      neurological disorders. SUBJECTS: Sixty-eight patients with cerebral spasticity
      of different aetiologies were treated with serial casting to relieve fixed
      contractures. INTERVENTION: Serial casting with either < 90 days (group A, 36
      joints, 24 patients) or > or = 90 days (group B, 85 joints, 44 patients) duration
      of illness and either < 12 (group 1, 49 joints, 25 patients) or > or = 12 (group
      2, 72 joints, 43 patients) Glasgow Coma Scale (GCS) scores. MAIN OUTCOME
      MEASURES: Percentage of normal maximum range of motion (ROM) at the completion of
      casting and one month after discontinuation, and number of complications due to
      casting procedure. RESULTS: No differences in ROM improvement between duration
      groups (F = 0.43, p = 0.51) and GCS groups (F = 1.3, p = 0.26) were observed.
      Complications in serial casting were found in 25.0% in group A, in 10.6% in group
      B (chi-squared = 4.2, p = 0.042), in 24.5% in group 1, and in 8.3% in group 2
      (chi-squared = 6.0, p = 0.014). CONCLUSION: This study suggests that serial
      casting in patients with longer illness duration and higher levels of
      consciousness provides improvements in ROM comparable with an earlier treatment
      in patients with more impaired consciousness, but results in a lower occurrence
      of complications.

PMID- 12785247
TI  - The Adult Memory and Information Processing Battery (AMIPB) test of information
      processing speed: a study of its reliability and feasibility in patients with
      multiple sclerosis.
AB  - OBJECTIVE: To investigate how useful the Adult Memory and Information Processing
      Battery Task A (AMIPB) is as a test of the speed of information processing in
      patients with multiple sclerosis (MS) by comparing various methods of presenting
      the test and assessing the reliability (test-retest and inter-rater) and utility
      of each version. DESIGN: Each patient was assessed twice verbally by the same
      assessor 1-2 weeks apart. Then 1-2 weeks later half were assessed by another
      observer, and half were assessed by the first observer using a written method.
      SETTING: A specialist young disabled unit. SUBJECTS: Thirty-three patients with
      MS. MEASURES: The AMIPB, the Short Memory-Orientation-Concentration Test (SOMC)
      and the Barthel ADL Index. RESULTS: The average (SD) number of correct responses
      after 4 min was 23.3 (18.6), median 21. The test-retest reliability (n = 24) of
      the 4-min AMIPB was high (r = 0.98) and the difference of the score ranged from 
      7 to 9: median 3, mean (SD) 1.88 (4.01) and interquartile range 0 to 3.25. The
      inter-observer reliability (n = 12) of the 4-min AMIPB was also high (r = 0.97)
      and the mean (SD) differences between scores were 4.3 (5.8), median 4, range +19
      to -2. The score at 60 seconds and the score at 240 seconds were highly
      correlated (r = 0.98). The scores obtained verbally and by writing were closely
      correlated (r = 0.99). CONCLUSIONS: The AMIPB used over 120 seconds with verbal
      responses is a reliable and reasonable test for major information-processing
      deficits.

PMID- 12785246
TI  - Interpreting change scores on the Amyotrophic Lateral Sclerosis Assessment
      Questionnaire (ALSAQ-40).
AB  - OBJECTIVES: To determine the amount of change over time on the five dimensions of
      the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
      that are subjectively meaningful to patients. Minimally important differences
      (MID), effect sizes (ES) and standardized response means (SRM) are calculated for
      respondents who indicate only a little change over the time of the study whilst
      mean change scores, ES and SRM statistics are calculated for those who indicated
      much change. DESIGN: Postal survey. Copies of the ALSAQ-40 were completed on two
      occasions three months apart. Respondents were also asked to indicate how much
      change they had experienced since baseline on each of the five domains of the
      questionnaire. SETTING: All patient members of the Motor Neurone Disease
      Association for England, Wales and Northern Ireland. SUBJECTS: Seven hundred and
      sixty-four patient members returned questionnaires at baseline and follow-up.
      RESULTS: For those reporting minor change since baseline results varied across
      dimensions. For example a MID was reflected in a change of 6.67 (SD 16.52) points
      for the Communication dimension, whilst for the Emotional functioning dimension
      the change was 2.67 (SD 15.45) points. Similarly ESs and SRMs varied considerably
      across dimensions. Mean change over time, ES and SRM statistics for those who
      reported that their health was much worse at follow-up were substantially larger:
      for example, mean changes ranged from 6.87 (SD 15.87) to 13.79 (SD 22.60).
      CONCLUSIONS: Results indicate the minimum magnitude of change that is
      subjectively meaningful to patients. Results indicate that smaller changes than
      have been suggested previously as significant have a subjectively meaningful
      adverse effect upon patients.

PMID- 12785248
TI  - The validity of patient and physician estimates of walking distance.
AB  - OBJECTIVE: To establish the validity of patient and physician estimates of
      maximum walking distance versus actual measured maximum walking distance. DESIGN:
      Assessment of concurrent validity (patient and physician estimates were compared
      with a gold standard measure at the same time). SETTING: University-affiliated
      rehabilitation department in a tertiary care hospital. SUBJECTS: A sequential
      sample of 31 patients over the age of 17 referred to the physical medicine and
      rehabilitation outpatients department between 1 May 2000 and 20 July 2001, who
      had at least some degree of walking difficulty. INTERVENTIONS: Patients and their
      physicians were asked to provide estimates of walking distance independently
      after a regular appointment prior to the patient being escorted along a pre
      measured walking course. MAIN OUTCOME MEASURES: Actual distance walked was
      compared with estimates using Pearson correlation coefficients. RESULTS: Pearson
      correlation coefficients for patient estimate versus actual was 0.789 (p < or =
      0.0001), and mean estimate of patient and physician estimates versus actual was
      0.812 (p < or = 0.0001). Physician estimate versus actual and patient estimate
      versus physician estimate were 0.349 and -0.139 (neither significant). Sixty
      seven per cent (20/30) of patients overestimated how far they thought they could
      walk versus 23% (7.30) of physicians who overestimated. Neither group were found
      to be 'good' estimators of maximal walking distance. CONCLUSIONS: Neither
      patients nor physicians provide valid estimates of maximal walking distance.
      Patients consistently overestimate their maximal walking distance, whereas
      physicians tend to underestimate. Interestingly, patients' estimates (although
      over inflated) do correlate well with actual walking distance, while physician
      estimates are not at all correlated. This study suggests that reliance on self
      reported or physician-estimated maximum walking distances (whether for clinical,
      research or other reasons) is potentially flawed.

PMID- 12785249
TI  - Reliability and validity of the Canadian Occupational Performance Measure in
      stroke patients.
AB  - OBJECTIVE: To research test-retest reliability and discriminant validity of the
      Canadian Occupational Performance Measure (COPM), a client-centred outcome
      measure, in stroke patients. DESIGN: The COPM was administered twice with a mean
      interval of eight days (SD 2.5, range 5-16). On both occasions the patient
      identified a maximum of five problems in daily activities. The problems of both
      interviews were compared. The problems identified during the first COPM were
      rated by the patient on a performance and satisfaction rating scale on both
      occasions. The individually identified items with use of the client-centred COPM
      were compared with the fixed items of standardized measures (Barthel Index,
      Frenchay Activities Index, Stroke Adapted Sickness Impact Profile-30, Euroqol 5D
      and Rankin Scale). SETTING: Patients were interviewed at their place of
      residence. SUBJECTS: Twenty-six stroke patients participated, 11 men and 15
      women, aged from 26 to 83 years (mean 68, SD 15). Twenty-four patients were six
      months, two patients were two months post stroke. RESULTS: Of the 115 problems
      identified during the first COPM, 64 (56%) were also identified the second time.
      Correlation coefficients for the scores were 0.89 (p < 0.001) for performance and
      0.88 (p < 0.001) for satisfaction. Of the individual problems identified with the
      COPM, 25% or less were present in the standardized measures. Correlations between
      the scores on the COPM and the standardized measures were low and nonsignificant,
      while all standardized measures correlated significantly with each other.
      CONCLUSIONS: Test-retest reliability of the COPM was moderate for the item pool
      but was good for the performance and satisfaction scores. Discriminant validity
      was confirmed. Many patient-unique problems identified with the COPM were not
      evaluated by standardized measures.

PMID- 12785250
TI  - Emotional well-being of close relatives to stroke survivors.
AB  - OBJECTIVE: To compare the well-being of stroke patients' relatives with that of a
      reference group, and to identify variables related to the well-being of the
      relatives. DESIGN: Cross-sectional study. SETTING: Outpatient hospital department
      and patients' and relatives' own homes. SUBJECTS: Fifty-four patients one year
      after a stroke and their closest relatives. A reference population consisted of
      419 elderly people drawn at random from the census files. OUTCOME MEASURES:
      Emotional well-being was assessed with the General Health Questionnaire (GHQ-20),
      and the perceived burden attributed to the care of the patient with the Caregiver
      Strain Index (CSI). The personal and instrumental activities of daily life (PADL
      and IADL), motor and cognitive functions of the patients were assessed with
      standardized tests. RESULTS: The relatives rated their well-being lower than the
      reference group rated theirs, the odds ratio (OR) being 5.6 (95% confidence
      interval (CI) 3.1-10) adjusted for age and gender. No association was found
      between the relatives' well-being and the motor, cognitive, PADL, IADL or other
      characteristics of the patients. Strong relationships were found between the CSI
      and the GHQ scores of the relatives, the OR (95% CI) for a poor GHQ score being
      2.4 (1.6-3.7) for each unit increase in CSI, adjusted for gender. CONCLUSIONS:
      Emotional well-being is influenced when a close relative gets a stroke. This
      seems to relate more strongly to the perceived burden of care than to objective
      characteristics of the patient.

PMID- 12785251
TI  - Wheelchair skills tests: a systematic review.
AB  - OBJECTIVE: To describe and compare the content, feasibility, outcome parameters,
      and clinimetric properties of the manual wheelchair skills tests reported in the
      literature. DESIGN: A systematic literature search was conducted in MEDLINE,
      EMBASE, PsychINFO and Current Contents. Tests were selected if they were
      observational tests, designed for subjects using hand-rim wheelchairs and were
      intended to assess wheelchair skill performance at the activity level. RESULTS:
      The search resulted in 34 papers, in which 24 different wheelchair skills tests
      were described. The skill most frequently included was wheelchair propulsion,
      consecutively followed by transferring, negotiating kerbs, ascending slopes,
      traversing tracks, sprinting and performing a wheelie. The three most frequently
      used outcome parameters were task performance time, independency of task
      performance, and physical strain during skill performance. Sensitivity to change
      was evaluated in three tests, validity in 10 tests, and reliability in nine
      tests. CONCLUSIONS: Many tests are applied to measure wheelchair skill
      performance using different tasks and outcome measures. This makes it difficult
      to compare study results. Consensus among researchers as to which skills must be
      included as well as to standardization of the use of measurement instruments will
      reduce this problem and will additionally lead to a better insight in the quality
      of tests.

PMID- 12785252
TI  - Life satisfaction several years after severe multiple trauma--a retrospective
      investigation.
AB  - OBJECTIVES: To describe the prevalence of self-reported changes in life
      satisfaction after multiple trauma, to analyse associations between satisfaction
      with life as a whole and with domains in life, and to identify important
      contributors for satisfaction with life. DESIGN: Retrospective follow-up study.
      SETTING: Rehabilitation hospital three years after multiple trauma. SUBJECTS:
      Sixty-nine subjects with severe multiple trauma (ISS > or = 16). MAIN OUTCOME
      MEASURES: Clinical examinations to reveal prevalences of impairments and
      disabilities. Questionnaires about satisfaction with life as a whole and eight
      domains of life, both for the time before trauma, and for the actual situation;
      sense of coherence (SOC-13); social network. RESULTS: A total of 87% experienced
      a decrease in at least one of the nine life satisfaction items from before to
      after trauma (six-graded scale). After trauma significantly fewer subjects
      reported to be satisfied with life as a whole, as well as the domains sexual
      life, ADL, contact with friends, leisure, vocational and financial situation.
      Satisfaction with family life and partner relationship did not decrease
      significantly. The most important domains after trauma were satisfaction with
      leisure, family life and vocation. Vocational and leisure disability after trauma
      were important determinants for satisfaction with life as a whole. A strong sense
      of coherence and sufficient social network quality had significant impact on
      satisfaction with life as a whole and some of the domain-specific satisfactions.
      CONCLUSIONS: Both personal resources (a strong sense of coherence) and the
      presence of a qualitatively sufficient social network can buffer the negative
      influence of disabilities on life satisfaction after trauma.

PMID- 12785253
TI  - Is sense of coherence stable after multiple trauma?
AB  - OBJECTIVES: To explore whether sense of coherence (SOC) is stable over time after
      multiple trauma. The associations between SOC and satisfaction with life as a
      whole, as well as aspects of psychological well-being, were explored. Finally, an
      overriding aim was to assess whether SOC has long-term prognostic value for
      global life satisfaction or psychological well-being. DESIGN: Prospective study.
      SETTING: Sunnaas Rehabilitation Hospital. SUBJECTS: Twenty-six subjects with
      severe multiple trauma, without neuropsychological deficits. MAIN OUTCOME
      MEASURES: Questionnaires that were answered at admission, at discharge and at
      follow-up 1-3 years after trauma were: Sense of Coherence Scale 13 items (SOC
      13), satisfaction with life as a whole, General Health Questionnaire 20 items
      (GHQ-20), Hospital Anxiety and Depression Scale (HAD). RESULTS: While median SOC
      scores were fairly stable, individual scores were not stable over time, and for
      some subjects showed large variations. SOC score had neither long-term prognostic
      value for satisfaction with life as a whole nor for psychological well-being, at
      least not in the first years after severe multiple trauma. However, SOC was
      closely associated with overall life satisfaction when measured simultaneously.
      Furthermore, a weak SOC correlated with scores on psychological distress, anxiety
      and depression. SOC scores were also significantly related to being or not being
      in a state of anxiety, but not to being or not being depressed. Global life
      satisfaction was considerably reduced from before trauma (reported at admission)
      to the time of follow-up. CONCLUSION: SOC was not stable over time after severe
      multiple trauma. SOC measured at admission could neither predict future
      satisfaction with life as a whole nor future psychological well-being. Measured
      simultaneously, overall life satisfaction and occurrence of anxiety were
      significantly associated with SOC.

PMID- 12785254
TI  - Risk perception of developing complex regional pain syndrome I.
AB  - This study investigated how members of a hand team perceive clinical signs after
      a fracture of the distal radius. The risk of developing complex regional pain
      syndrome I (CRPS-I) was assessed on a 100-mm straight line based on clinical
      signs 5 weeks, 7 weeks and 10 weeks after the accident. Members of the hand team
      perceived clinical signs significantly differently.

PMID- 12785255
TI  - Reliability of the Dutch Pediatric Evaluation of Disability Inventory (PEDI).
AB  - OBJECTIVE: To evaluate the reliability of the Dutch version of the Pediatric
      Evaluation of Disability Inventory (PEDI), an instrument for measuring functional
      status (capability and performance in self-care, mobility and social function) of
      young children using parent interviews. DESIGN: Inter-interviewer reliability was
      studied after scoring audiotaped interviews by a second researcher. For test
      retest reliability the same parent was interviewed twice within three weeks; in
      inter-respondent reliability both parents of a child were interviewed
      independently within a few days. On item level, percentage identical scores were
      computed, and on scale level intraclass correlation coefficients (ICC) and
      Cronbach's alphas were calculated. SUBJECTS: Parents of 63 nondisabled and 53
      disabled (various diagnosis) children aged between 7 and 88 months were
      interviewed. RESULTS: On scale level, all ICCs were above 0.90 and Cronbach's
      alpha was 0.89 for the self-care domain, 0.74 for the mobility domain and 0.87
      for the social function domain. On item level for the Functional Skills Scale,
      the mean percentage identical scores varied from 89 to 99, and for the Caregiver
      Assistance Scale from 54 to 90. Different scores between interviewers resulted
      partially from ambiguous interpretation of the item and/or the explanation.
      CONCLUSIONS: Although small adaptations have to be made, the psychometric
      properties of the Dutch PEDI are found to be good.

PMID- 12785257
TI  - Stripes and superconductivity in cuprates--is there a connection?

PMID- 12785256
TI  - Quantum control of gas-phase and liquid-phase femtochemistry.
AB  - Active control of chemical reactions on a microscopic (molecular) level, that is,
      the selective breaking or making of chemical bonds, is an old dream. However,
      conventional control agents used in chemical synthesis are macroscopic variables
      such as temperature, pressure or concentration, which gives no direct access to
      the quantum-mechanical reaction pathway. In quantum control, by contrast,
      molecular dynamics are guided with specifically designed light fields. Thus it is
      possible to efficiently and selectively reach user-defined reaction channels. In
      the last years, experimental techniques were developed by which many
      breakthroughs in this field were achieved. Femtosecond laser pulses are
      manipulated in so-called pulse shapers to generate electric field profiles which
      are specifically adapted to a given quantum system and control objective. The
      search for optimal fields is guided by an automated learning loop, which employs
      direct feedback from experimental output. Thereby quantum control over gas-phase
      as well as liquid-phase femtochemical processes has become possible. In this
      review, we first discuss the theoretical and experimental background for many of
      the recent experiments treated in the literature. Examples from our own research
      are then used to illustrate several fundamental and practical aspects in gas
      phase as well as liquid-phase quantum control. Some additional technological
      applications and developments are also described, such as the automated
      optimization of the output from commercial femtosecond laser systems, or the
      control over the polarization state of light on an ultrashort timescale. The
      increasing number of successful implementations of adaptive learning techniques
      points at the great versatility of computer-guided optimization methods. The
      general approach to active control of light-matter interaction has also
      applications in many other areas of modern physics and related disciplines.

PMID- 12785258
TI  - Femtochemistry of trans-azomethane: a combined experimental and theoretical
      study.
AB  - The dissociation dynamics of trans-azomethane upon excitation to the S,(n, pi)
      state with a total energy of 93 kcalmol-1 is investigated using femtosecond
      resolved mass spectrometry in a molecular beam. The transient signal shows an
      opposite pump-probe excitation feature for the UV (307 nm) and the visible (615
      nm) pulses at the perpendicular polarization in comparison with the signal
      obtained at the parallel polarization: The one-photon symmetry-forbidden process
      excited by the UV pulse is dominant at the perpendicular polarization, whereas
      the two-photon symmetry-allowed process initiated by the visible pulse prevails
      at the parallel polarization. At the perpendicular polarization, we found that
      the two C-N bonds of the molecule break in a stepwise manner, that is, the first
      C-N bond breaks in approximately 70 fs followed by the second one in
      approximately 100 fs, with the intermediate characterized. At the parallel
      polarization, the first C-N bond cleavage was found to occur in 100 fs with the
      intensity of the symmetry-allowed transition being one order of magnitude greater
      than the intensity of the symmetry-forbidden transition at the perpendicular
      polarization. Theoretical calculations using time-dependent density functional
      theory (TDDFT) and the complete active space self-consistent field (CASSCF)
      method have been carried out to characterize the potential energy surface for the
      ground state, the low-lying excited states, and the cationic ground state at
      various levels of theory. Combining the experimental and theoretical results, we
      identified the elementary steps in the mechanism. The initial driving force of
      the ultrafast bond-breaking process of trans-azomethane (at the perpendicular
      polarization) is due to the CNNC torsional motion initiated by the vibronic
      coupling through an intensity-borrowing mechanism for the symmetry-forbidden n-pi
      transition. Following this torsional motion and the associated molecular symmetry
      breaking, an S0/S1 conical intersection (CI) can be reached at a torsional angle
      of 93.1 degrees (predicted at the CASSCF(8.7)/cc-pVDZ level of theory). Funneling
      through the S0/S1, CI could activate the asymmetric C-N stretching motion, which
      is the key motion for the consecutive C-N bond breakages on the femtosecond time
      scale.

PMID- 12785259
TI  - A test for the number of coupled spins I = 1/2 in magic-angle-spinning solids:
      zero-quantum recoupling of multiple-quantum coherences.
AB  - Current methodologies for estimating the number of coupled spins I = 1/2 in
      solids are based upon the maximum multiple-quantum order that can be observed.
      This strategy establishes a clear lower bound on the number of coupled spins I =
      1/2. However, it is difficult to ascertain the exact number of coupled spins,
      since the absence of a peak could be due either to the limited size of the spin
      system or to the experimental difficulty of exciting high-quantum orders and
      recovering those coherences into detectable signals. Herein, a supplementary test
      is proposed that allows one to determine whether a given coherence has the
      highest possible order in the spin system. The sample is subjected to magic-angle
      spinning and the behaviour of the coherence under a rotor-synchronised spin-echo
      sequence is compared to its behaviour under a zero-quantum recoupling sequence. A
      similar decay of the coherence in these two experiments is strong evidence for
      the coherence order being the maximum possible. We propose applications to
      biomolecular solid-state NMR spectroscopy.

PMID- 12785260
TI  - Adsorption of CO2 and coadsorption of H and CO2 on potassium-promoted Cu(115).
AB  - The influence of potassium, in the submonolayer regime, on the adsorption and
      coadsorption of CO2 and H on a stepped copper surface, Cu(115), has been studied
      by photoelectron spectroscopy, temperature-programmed desorption, and work
      function measurements. Based on the fast recording of C 1s and O 1s core-level
      spectra, the uptake of CO2 on K/Cu(115) surfaces at 120 K has been followed in
      real time, and the different reaction products have been identified. The K 2p3/2
      peak exhibits a chemical shift of -0.4 eV with CO2 saturation, the C 1s peaks of
      the CO3 and the CO species show shifts of -0.8 and -0.5 eV, respectively, and the
      C 1s peak of the physisorbed CO2 exhibits no shift. The effects of gradually
      heating the CO2/K/Cu(115) surface include the desorption of physisorbed CO2 at
      143 K; the desorption of CO at 193 K; the ordering of the CO3 species, and
      subsequently the dissociation of the carbonate with desorption at 520-700 K.
      Formate, HCOO-, was synthesized by the coadsorption of H and CO2 on the K/Cu(115)
      surface at 125 K. Formate formed exclusively for potassium coverages of less than
      0.4 monolayer, whereas both formate and carbonate were formed at higher
      coverages. The desorption of formate-derived CO2 took place in the temperature
      range 410-425 K and carbonate-derived CO2 desorbed at 645-660 K, depending on the
      potassium coverage.

PMID- 12785261
TI  - Studies on intra-supramolecular and intermolecular electron-transfer processes
      between zinc naphthalocyanine and imidazole-appended fullerene.
AB  - Spectroscopic, computational, redox, and photochemical behavior of a self
      assembled donor-acceptor dyad formed by axial coordination of zinc
      naphthalocyanine, ZnNc, and fulleropyrrolidine bearing an imidazole coordinating
      ligand (2-(4'-imidazolylphenyl)-fulleropyrrolidine, C60Im) was investigated in
      noncoordinating solvents, toluene and o-dichlorobenzene, and the results were
      compared to the intermolecular electron transfer processes in a coordinating
      solvent, benzonitrile. The optical absorption and ab initio B3 LYP/3-21G(*)
      computational studies revealed self-assembled supramolecular 1:1 dyad formation
      between the ZnNc and C60Im entities. In the optimized structure, the HOMO was
      found to be entirely located on the ZnNc entity while the LUMO was found to be
      entirely on the fullerene entity. Cyclic voltammetry studies of the dyad
      exhibited a total of seven one-electron redox processes in o-dichlorobenzene,
      with 0.1 M tetrabutylammonium perchlorate. The excited-state electron-transfer
      processes were monitored by both optical-emission and transient-absorption
      techniques. Direct evidence for the radical-ion-pair (C60Im.-:ZnNC.+) formation
      was obtained from picosecond transient-absorption spectral studies, which
      indicated charge separation from the singlet-excited ZnNc to the C60Im moiety.
      The calculated rates of charge separation and charge recombination were 1.4 x
      10(10) s-1 and 5.3 x 10(7) s-1 in toluene and 8.9 x 10(9) s-1 and 9.2 x 10(7) s-1
      in o-dichlorobenzene, respectively. In benzonitrile, intermolecular electron
      transfer from the excited triplet state of ZnNc to C60Im occurs and the second
      order rate constant (kqtriplet) for this quenching process was 5.3 x 10(8)M-1s-1.

PMID- 12785262
TI  - Ship-in-a-bottle synthesis of a large guest occupying two Y zeolite neighbour
      supercages: characterisation and photocatalytic activity of the encapsulated
      bipyrylium ion.

PMID- 12785263
TI  - Photocatalytic and photoelectrochemical properties of nitrogen-doped titanium
      dioxide.

PMID- 12785264
TI  - Molecular-template-mediated chemical decoration.

PMID- 12785265
TI  - Molecular arrangement of fatty acids at the solid-liquid interface visualized by
      chemical decoration.

PMID- 12785266
TI  - Polaron pair versus bipolaron on oligothiophene chains: a theoretical study of
      the singlet and triplet states.

PMID- 12785267
TI  - Cholesteric networks based on lyotropic mixtures.

PMID- 12785268
TI  - Electrosurface phenomena at polymer films for biosensor applications.
AB  - Electrosurface phenomena at thin polymer films utilized in the preparation of
      biosensors have been studied by use of the Microslit Electrokinetic set-up. For
      the investigated polymer layers (aminodextran, carboxylated dextran,
      diaminopoly(ethylene glycol), dicarboxypoly(ethylene glycol), biotinylated
      poly(ethylene glycol), and streptavidin on biotinylated poly(ethylene glycol),
      the charge formation in aqueous electrolyte solutions was found to depend on the
      pH value, that is, OH- and H3O+ are the charge determining ions. The isoelectric
      points obtained from zeta potential versus pH plots could be utilized to draw
      conclusions on the introduction of acidic or basic groups and on the degree of
      molecular surface coverage, respectively. The hydrodynamically mobile charge
      reflected by the magnitude of the zeta potential contributed to only about 6% or
      less of the total surface conductivity of the polymer layers. The experimental
      determination of the total surface conductivity was found to provide valuable
      information on structural features of biosensor interfaces in aqueous
      environments.

PMID- 12785269
TI  - Pt nanoparticles dispersed in a mesostrucured silica matrix: towards self
      organized 3D nanocomposite.

PMID- 12785270
TI  - Relativistic DFT calculations of polyoxotungstate 183W NMR spectra: insight into
      their solution structure.

PMID- 12785272
TI  - How diradicaloid is a stable diradical?

PMID- 12785271
TI  - Supercritical carbon dioxide-induced phase changes in (ionic liquid, water and
      ethanol mixture) solutions: application to biphasic catalysis.

PMID- 12785273
TI  - Trapping metal nanoclusters in "soap and water" soft crystals.

PMID- 12785274
TI  - Pediatric emergency medicine draws on the expertise of pediatrics and emergency
      medicine in forming the foundation of growing body of clinical expertise.

PMID- 12785275
TI  - Poisoned child: emergency room management.
AB  - Poisoning is one of the commonest pediatric emergencies. Most of poisonings in
      children below 5 years of age, are accidental and fortunately trivial, related to
      their exploratory nature. However a poisoned child may present as an acute
      emergency with or without multisystem involvement. The initial phase of
      management focuses on support of airways, breathing and cardiac function (ABCD of
      Resuscitation). The second phase includes Evaluation and Detoxification phase.
      The Evaluation phase involves identification and severity of toxic exposure.
      Recognizing a Toxidrome (constellation of the signs and symptoms seen with the
      ingestion of a particular poison) is particularly very helpful when the child
      presents with an unknown poisoning. Detoxification should proceed simultaneously.
      The current literature suggests that activated charcoal is the mainstay of GI
      decontarmination. Whole bowel Irrigation is a new addition to the armamentarium
      of GI decontamination. At present antidotes are available for few toxins only so
      the management remains supportive for most poisons.

PMID- 12785276
TI  - Animal bites: the current management guidelines.
AB  - Rabies is a major public health problem in India. It is mainly transmitted by
      stray dogs, which form an overwhelming population in the country. Dogs are
      responsible for upto 95% of animal bites requiring antirabies treatment. In view
      of the exceptionally high fatality rate of human rabies, the prevention of
      infection after exposure is of utmost importance. With the availability of safe
      and effective tissue culture vaccines prevention of this dreaded disease is
      virtually assured by immediate and appropriate post exposure treatment. This is a
      three pronged approach including proper wound management, judicious use of
      antirabies serum and modern tissue culture vaccines. In India, Neural Tissue
      Vaccine is still used for post exposure treatment in public sector, though
      effective, this vaccine has serious side effects. The production and use of
      tissue culture vaccine should be encouraged with the aim to phase out neural
      tissue vaccine. WHO recommends use of intradermal route of inoculation of Tissue
      Culture Vaccine which makes the treatment very economical. However, this route as
      yet, is not approved by Drug Controller, Government of India (DCGI). There are no
      uniform guidelines for management of animal bite cases in India. In this article
      an attempt is made to discuss various aspects of animal bite management.

PMID- 12785277
TI  - Status epilepticus: emergency management.
AB  - Status Epilepticus (SE) is a medical emergency and requires prompt and aggressive
      treatment. Stabilization of airway, breathing and circulation and expeditious
      termination of seizures are immediate goals. Intravenous benzodiazepines
      diazepam, midazolam or lorazepam and phenytoin are the first line drugs
      recommended for termination of seizures. Diazepam (or midazolam), thiopental and
      propofol infusion are useful for control of Refractory SE (RSE). Newer drugs are
      being investigated for use in SE. We prefer diazepam infusion. In children the
      mortality from SE ranges from 3-10% and the morbidity is twice. Mortality and
      morbidity are highest with SE associated with CNS infections, which is the most
      important cause of SE in our country. The outcome depends on the underlying
      etiology, age, rapidity of SE and adequacy of care. Adherence to a time-framed
      protocol in the emergency department helps in improving the final outcome.

PMID- 12785278
TI  - Stroke in children.
AB  - Stroke is a thrombohemorrhagic disorder of the central nervous system, with a
      fairly good outcome in pediatric age group except for the infancy period. In
      children ischemic type is more common than hemorrhagic type. Though it is
      difficult to distinguish between thrombotic and embolic phenomenon but it is
      largely due to cardiovascular lesions, at times it may be the first symptom to
      appear. The signs and symptoms also appear to be vague in children, hence
      difficult to pinpoint the etiology. The treatment of stroke is largely for
      stabilization of the patient, but it is very important to know the cause to
      prevent future strokes. Use of heparin in ischemic stroke is very promising and
      thrombolytic therapy is under trial.

PMID- 12785279
TI  - Acute asthma in emergency room.
AB  - Acute asthmatic exacerbation is one of the commonest emergencies seen in the
      pediatric age group. Viral infections are the most important triggers which set
      up the inflammatory reaction in the bronchial mucosa. GINA 2002 guidelines for
      assessing the severity and management are very useful for day to day practice.
      There is evidence to support the view that metered dose inhaler alongwith spaceor
      with or without mask is as effective as the standard doses of beta-2 agonists
      given by nebulizer. Ipratrpium bromide adds to the benefits of short acting beta
      2 agonists. Systemic steroids should be started early. Early introduction of l/v
      beta-2 agonists and trial of l/v magnesium sulfate in non-responders have been
      recently recommended. Intravenous aminophylline can be tried in addition to full
      dose beta-2 agonists in those who reach the PICU. A close watch on the patient by
      monitoring clinical parameters, pulse oximeter, arterial blood gases and peak
      flow rate help in deciding whether there is need to further step up the therapy.
      Non-conventional measures like ketamine should be tried only under constant
      monitoring.

PMID- 12785280
TI  - Pediatric Advanced Life Support (PALS): the current guidelines.
AB  - Every 5 years the American Heart Association (AHA) updates the Guidelines for CPR
      and Emergency Cardiovascular Care (ECC). The ECC Guidelines 2000 incorporates all
      the current consensus of experts, from not only a variety of disciplines, but
      also a variety of countries and cultures and is evidence based. The new
      Guidelines emphasize interventions to reduce the risk of sudden deaths, early
      identification of respiratory failure and shock and implementation of Advanced
      Life Support (ALS) to treat respiratory and cardiac arrest.

PMID- 12785281
TI  - Migraine: a common cause of headache.
AB  - Acute headaches in a child evoke anxiety in parents, of a possible catastrophic
      underlying intracranial pathology. Headaches constitute up to 2 to 6% of all
      emergency room visit. The prevalence of migraine is increasing. The majority of
      children have migraine without aura, and about one fifth have migraine with aura.
      Complicated migraine presents with dramatic neurologic signs and remains a
      diagnosis of exclusion. Children with migraine require reassurance, modification
      of life style and food habits, combined with judicious use of simple abortive
      medications and antiemetics. Prophylaxis in migraine is recommended for frequent
      or severe attacks and in complicated migraine.

PMID- 12785282
TI  - Evaluation and management of the febrile infant in the emergency department.
AB  - Treating the febrile infant strikes fear in all of us. The source of fever in a
      very young infant may be a serious bacterial infection. A thorough physical
      examination is just the beginning of a complete evaluation of a febrile infant.
      This article discusses appropriate testing, treatment, and disposition of these
      patients. Within the age group addressed in this article, diagnosis and treatment
      of febrile neonates (i.e. age < 1 month) are the least controversial. Febrile
      neonates warrant thorough evaluation, complete diagnostic testing, and aggressive
      inpatient treatment with i.v. antibiotics. Management of infants between 1-3
      months of age may be guided by clinical evaluation and laboratory investigations.
      In infants above 3 months of age, the clinical assessment can direct regarding
      laboratory testing and treatment in most of the cases.

PMID- 12785284
TI  - Unique general anesthetic binding sites within distinct conformational states of
      the nicotinic acetylcholine receptor.
AB  - General anesthesia is a complex behavioral state provoked by the pharmacological
      action of a broad range of structurally different hydrophobic molecules called
      general anesthetics (GAs) on receptor members of the genetically linked ligand
      gated ion channel (LGIC) superfamily. This superfamily includes nicotinic
      acetylcholine (AChRs), type A and C gamma-aminobutyric acid (GABAAR and GABACR),
      glycine (GlyR), and type 3 5-hydroxytryptamine (5-HT3R) receptors. This review
      focuses on recent advances in the localization of GA binding sites on
      conformationally and compositionally distinct AChRs. The experimental evidence
      outlined in this review suggests that: 1. Several neuronal-type AChRs might be
      targets for the pharmacological action of distinct GAs. 2. The molecular
      components of a specific GA binding site on a certain receptor subtype are
      different from the structural determinants of the locus for the same GA on a
      different receptor subtype. 3. There are unique binding sites for distinct GAs in
      the same receptor protein. 4. A GA can activate, potentiate, or inhibit an ion
      channel, indicating the existence of more than one binding site for the same GA.
      5. The affinity of a specific GA depends on the conformational state of the
      receptor. 6. GAs inhibition channels by at least two mechanisms, an open-channel
      blocking and/or an allosteric mechanism. 7. Certain GAs may inhibit AChR function
      by competing for the agonist binding sites or by augmenting the desensitization
      rate.

PMID- 12785283
TI  - Current trends in wound management.
AB  - Laceration and wound are common emergencies for which children are brought to
      emergency room. Pediatricians can manage most of these himself. Recently few more
      methods have become available for wound closure, which are very useful to
      pediatricians in their office settings. This article stresses on the current
      trends in wound management. A tidy wound can be repaired primarily while untidy
      wound requires conversion to tidy wound before closure. Host and environmental
      factors, which can affect wound healing, should be identified and managed
      accordingly. Parental presence can be very useful in certain cases. Wound should
      be examined and irrigated thoroughly to remove foreign bodies and debris.
      Associated injuries should be assessed and treated appropriately. Suturing,
      staplers or tissue adhesives can do the wound closure. Last method is
      particularly useful in pediatric office settings. Antibiotics are needed in
      certain selected conditions.

PMID- 12785286
TI  - Behavioral measures of alcohol self-administration and intake control: rodent
      models.
AB  - This review provides a brief historical overview of the behavioral paradigms that
      have been used to study alcohol consumption using rats as subjects, and then
      critically evaluates these models' ability to address the complexities involved
      in ethanol-seeking and self-administration. Many of these models have been
      influenced by a "behavioral pharmacology" approach, and therefore have studied
      oral ethanol reinforcement in a manner similar to food and water reinforcement.
      Because of this, these models have failed to adequately assess the complex
      seeking responses that are an integral part of ethanol-motivated behaviors. As an
      alternative, an appetitive-consummatory approach that procedurally separates and
      measures the two phases of behavior is suggested, and recent data using this
      model are reviewed. It is important that animal models that are to be used to
      evaluate underlying physiological mechanisms of the control of ethanol self
      administration accurately address all of the complex behaviors that are involved
      in intake control.

PMID- 12785285
TI  - Signaling molecules and receptor transduction cascades that regulate NMDA
      receptor-mediated synaptic transmission.

PMID- 12785287
TI  - Dopaminergic mouse mutants: investigating the roles of the different dopamine
      receptor subtypes and the dopamine transporter.

PMID- 12785288
TI  - Drosophila melanogaster, a genetic model system for alcohol research.
AB  - In its natural environment, which consists of fermenting plant materials, the
      fruit fly Drosophila melanogaster encounters high levels of ethanol. Flies are
      well equipped to deal with the toxic effects of ethanol; they use it as an energy
      source and for lipid biosynthesis. The primary ethanol-metabolizing pathway in
      flies involves the enzymes alcohol dehydrogenase (ADH) and acetaldehyde
      dehydrogenase (ALDH); their role in adaptation to ethanol-rich environments has
      been studied extensively. The similarity between Drosophila and mammals is not
      restricted to the manner in which they metabolize ethanol; behaviors elicited by
      ethanol exposure are also remarkably similar in these organisms. Flies show signs
      of acute intoxication, which range from locomotor stimulation at low doses to
      complete sedation at higher doses, they develop tolerance upon intermittent
      ethanol exposure, and they appear to like ethanol, showing preference for ethanol
      containing media. Molecular genetic analysis of ethanol-induced behaviors in
      Drosophila, while still in its early stages, has already revealed some surprising
      parallels with mammals. The availability of powerful tools for genetic
      manipulation in Drosophila, together with the high degree of conservation at the
      genomic level, make Drosophila a promising model organism to study the mechanism
      by which ethanol regulates behavior and the mechanisms underlying the organism's
      adaptation to long-term ethanol exposure.

PMID- 12785289
TI  - Impact of a course on human sexuality and adolescence.
AB  - OBJECTIVE: This study was conducted as part of a course on Human Sexuality and
      Adolescence for school children to ascertain the prior knowledge of children,
      source of their knowledge and whether the course was a felt need of the children.
      METHOD: Students were given a questionnaire before the course. Few selected
      questions were asked again after the last session. The course was conducted in a
      private co-educational English medium school in urban Bangalore involving 392
      students 13-15 years of age. The course was designed by the authors and dealt
      with anatomy, physiology, social and psychological aspects of growing up, HIV and
      contraception. RESULTS: 55-70% of class VIII, IX and X students had learnt about
      sex from friends, 30% from movies, 15% from text books and only 10% from parents.
      Misconceptions about anatomy, childbirth, HIV were common. 90% of tenth class
      students felt that education in human sexuality was necessary. CONCLUSION: In
      spite of chapters on reproduction in textbooks, children turn to peers or media
      to gather information on sexuality. Education in human sexuality is required in
      our schools, as this need is currently not being addressed adequately in our
      society.

PMID- 12785290
TI  - Prevalence and correlates of diarrhea.
AB  - OBJECTIVE: The present study aimed to estimate the prevalence of acute diarrhea
      and its correlates in remote rural villages of south Pakistan. METHODS: The
      authors selected 1878 children less than 3 years of age through stratified random
      sampling from 64 villages having the number of children enrolled proportionate to
      the size of each village, in rural Sindh, Pakistan. Trained field workers
      completed child physical measurements and maternal interviews. RESULTS: Among the
      children examined, 961 (51%) had diarrhea in the preceding 14 days prior to the
      date of survey. The prevalence of diarrhea was marginally higher among girls than
      boys (53% versus 49%, odds ratio 1.18, 95% CI 0.98, 1.41). The factors related
      with higher prevalence of diarrhea were lack of education of mother, lack of
      exclusive breast feeding, breast feeding for less than one year, roundworm
      infestation, low weight-for height, night blindness, female sex and number of
      older siblings more than 2 in the family. CONCLUSION: This study demonstrated
      that the acute diarrhea is major problem among children in rural Pakistan.
      Appropriate intervention programmes should be formulated focused on identified
      risk factors.

PMID- 12785291
TI  - Serum immunoglobulin E in early childhood wheezing.
AB  - OBJECTIVE: To study the serum Ig E levels in patients presenting with wheezing
      under the age of 24 months. METHODS: The study was conducted on 38 cases and 35
      controls. The children presenting with first attack of wheezing were clinically
      considered as bronchiolitis and those with recurrent attacks with positive
      history of atopy in the patient or in their first degree relatives were
      considered as bronchial asthma. The Ig E estimation was done by immune assay
      method. RESULTS: The mean serum Ig E was significantly higher in asthma patients
      (p < 0.001). It was also higher in bronchiolitis patients but the difference was
      not statistically significant. However, 26 per cent of these patients had values
      above 1 SD of the control mean. These patients were considered as potential cases
      of asthma. CONCLUSION: The determination of serum Ig E may be of value in
      identifying those children presenting with first wheezing attack, who may develop
      asthma in future. Only a long-term follow-up of these patients can give an answer
      to the postulation that raised Ig E level at the time of first viral lower
      respiratory tract infection is a potential marker for the development of
      recurrent wheezing in later life.

PMID- 12785292
TI  - Knowledge of diarrhea management among rural practitioners.
AB  - OBJECTIVE: To determine diarrhea management in rural practitioners. METHODS: This
      study was conducted among the RMP's of 4 blocks of Aligarh. Pre-coded
      questionnaire was completed and educational programme followed. 91% were
      prescribing ORS in various combinations, but only 9.8% were advising ORS and
      feeding as standard management of diarrhea. Only 12.8% could name a WHO ORS brand
      and 50% were giving wrong instructions for preparation. 95% were advising
      inadequate amounts of ORS. Only 43.5% were advising feeding during diarrhea but
      86.6% were advising to continue breastfeeding. On an average every 3rd to 4th
      patient was administered IVF's. 52% felt that drugs should be prescribed.
      RESULTS: 90% and 55.3% of RMPs could identify diarrhea and key signs of
      dehydration. CONCLUSION: There is a need for hands on training for the
      practitioners and education of the masses regarding proper management of
      diarrhea.

PMID- 12785293
TI  - Biochemical abnormalities in neonatal seizures.
AB  - OBJECTIVE: The presence of seizure does not constitute a diagnoses but it is a
      symptom of an underlying central nervous system disorder due to systemic or
      biochemical disturbances. Biochemical disturbances occur frequently in the
      neonatal seizures either as an underlying cause or as an associated abnormality.
      In their presence, it is difficult to control seizure and there is a risk of
      further brain damage. Early recognition and treatment of biochemical disturbances
      is essential for optimal management and satisfactory long term outcome. METHODS:
      The present study was conducted in the department of pediatrics in IGMC Shimla on
      59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases.
      RESULT: Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal
      seizures, most common being hypocalcaemia followed by hypoglycemia, other
      metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical
      abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates.
      Associated metabolic abnormalities were observed more often with Hypoxic-ischemic
      encephalopathy (11 out of 19) cases and hypoglycemia was most common in this
      group. CONCLUSION: No infant had hyponateremia, hyperkelemia or low zinc level.

PMID- 12785294
TI  - Cefpodoxime: pharmacokinetics and therapeutic uses.
AB  - Cefpodoxime is a semi-synthetic, third generation cephalosporin. The drug is
      available for use as a prodrug-Cefpodoxime proxetil, which is absorbed readily
      from the gut. It reaches adequate levels exceeding the MIC in most of the body
      fluids. It is excreted by kidneys, unchanged. Dose needs adjustment in
      compromised renal function. The drug is active against common gram-positive cocci
      like staphylococci including penicillinase producing strains, streptococci and
      gram negative bacteria like Hemophilus, E. coli, Klebsiella, Moraxella,
      Meningococci, Gonococci etc. The drug is useful in common upper and lower
      respiratory tract infections, sinusitis, and otitis media. The drug is also used
      in skin and soft tissue infections, urinary tract infection and respiratory tract
      infection. Cefpodoxime is being used as a step down from parenteral
      cephalosporin. The recommended dose is 8-10 mg/kg/d in a single or two doses.
      Different schedules have been given for different infections. The drug is safe,
      effective as a short course (5 vs. 10 days). With a low incidence of side
      effects, and twice a day dosing, it proves to be a useful drug.

PMID- 12785295
TI  - Urinary tract infections are a common bacterial infection in children.

PMID- 12785296
TI  - Management of urinary tract infections.
AB  - Urinary tract infection (UTI) is common in childhood. It may result in long-term
      complications due to renal scaring. Younger children are at higher risk of renal
      scarring. The diagnosis of UTI is based on urine culture. The bacterial count for
      diagnosis of UTI depends on the method of urine collection. Urinalysis is useful
      for making a presumptive diagnosis of UTI and allows initiation of empirical
      treatment in high-risk patients, after urine culture has been obtained. The
      treatment of UTI is guided by the severity of illness and age of the patient.
      Following a UTI, investigation should be performed to identify an underlying
      urinary tract anomaly. Recurrence of UTI occurs in 30-50% children. Important
      predisposing factors include VUR, urinary tract obstruction, voiding dysfunction
      and constipation. Vesicoureteric reflux (VUR) is seen in 30-50% children with
      UTI. The cornerstone of management of VUR is long-term antibiotic prophylaxis,
      which has been found to be as effective as surgical reimplantation.

PMID- 12785297
TI  - Vesicoureteric reflux and reflux nephropathy.
AB  - Reflux nephropathy i.e. renal scarring associated with vesico-ureteric reflux
      (VUR) and urinary tract infection (UTI) was originally considered an acquired
      disease. The renal scarring seems to get worse with recurrent urine infections
      especially in the young. Therefore, in the past much effort was undertaken to
      correct the VUR surgically and minimize the number of recurrent urinary tract
      infections by antibiotic prophylaxis with the hope of reducing if not arresting
      the onset of complications that follow i.e. hypertension and renal failure.
      However, it is now becoming clear that reflux nephropathy encompass at least two
      major categories of disease; "acquired" renal scarring secondary to UTI and VUR
      predominantly affecting females and "congenital" scarring with dysplastic
      features associated with prenatal VUR but with no infection and predominantly
      affecting boys. The latter is much less common but is disproportionately
      represented in the group of patients with reflux nephropathy that go on to
      develop renal failure. Unfortunately, the susceptibility to renal scarring, the
      onset of hypertension and progression to renal failure seems to be significantly
      influenced by genetic factors and hence measures undertaken to prevent recurrence
      of UTI may not change the ultimate outcome although it will certainly improve the
      comfort of the individual. Therefore, the extensive investigation and management
      routines adopted today in these children may not be cost-effective in preventing
      end stage renal disease in VUR. The progression to renal failure, however, can be
      delayed but not halted with adequate control of high blood pressure and hence the
      need for life long follow-up.

PMID- 12785298
TI  - Nocturnal enuresis.
AB  - Nocturnal enuresis is a benign condition, yet needs treatment to relieve the
      child and parents of the accompanying anxiety and the stigma attached to it. It
      is defined as normal nearly complete evacuation of the bladder at a wrong place
      and time at least twice a month after the fifth year of life. The underlying
      cause of enuresis is functional and various proposed pathophysiological
      mechanisms like maturational delay, genetics, role of sleep, antidiuretic
      hormone, and bladder capacity are discussed. These factors have a bearing on the
      management. As no treatment plan is ideal, various treatment modalities currently
      available including good supportive care are elaborated and a plan of management
      discussed.

PMID- 12785299
TI  - Renal transplantation.
AB  - Renal transplantation offers the best renal replacement therapy for most children
      with end stage renal disease improving their potential for growth and nutrition,
      neurodevelopment and quality of life. Advances in organ retrieval and
      preservation, improved surgical techniques, newer immunosuppressive drugs and
      prevention and treatment of infections have significantly improved patient and
      graft survival. The absolute requirements for a transplant are compatible blood
      group and a negative cytotoxic crossmatch. The immunosuppressive drugs most often
      used are cyclosporin A (or tacrolimus), azathioprine (or mycophenolate mofetil)
      and prednisone. Complications following transplantation include episodes of acute
      rejection, serious bacterial and viral infections, hypertension and recurrence of
      primary disease in the allograft. Each centre must have standard protocols for
      pre-transplant evaluation, management of immunosuppression and prevention of
      infections. Socio-economic factors should be carefully evaluated before offering
      transplantation to children in developing countries. Preemptive transplantation
      from a living donor may be a more viable option for these children.

PMID- 12785300
TI  - Dizygotic twins with myelomeningocele.
AB  - Among the neural tube defects incidence of spinabifida and myelomeningocele is
      less in twins compared to singletons. This article reports a case of dizygotic
      twins with myelomeningocele, a rare occurrence. Possible association of twining
      and neural tube defects and its impact on genetic counseling in such cases has
      been discussed.

PMID- 12785301
TI  - Congenital fibrolipoma of anal canal.
AB  - Although rare, congenital lipomatosis presents during first few months of life as
      large sub-cutaneous fatty masses on chest with extension into skeletal muscle
      bundles. Only a few such cases have been reported in the literature. A rare case
      of congenital fibrolipoma of anal canal in a 3-day-old male child is being
      documented in the present report.

PMID- 12785302
TI  - Erythropoietin in anemia of prematurity.

PMID- 12785303
TI  - Kuppuswamy's socioeconomic status scale--a revision.

PMID- 12785304
TI  - Streptacidiphilus gen. nov., acidophilic actinomycetes with wall chemotype I and
      emendation of the family Streptomycetaceae (Waksman and Henrici (1943)AL) emend.
      Rainey et al. 1997.
AB  - The taxonomic position of acidophilic actinomycetes selectively isolated from
      acidic soils and litter was examined using a polyphasic approach. The distinct
      16S rDNA phyletic branch formed by representative strains was equated with
      related monophyletic clades that corresponded to the genera Kitasatospora and
      Streptomyces. The acidophilic isolates also exhibited a distinctive pH profile, a
      unique 16S rDNA signature, and contained major amounts of LL-diaminopimelic acid,
      galactose and rhamnose in whole-organism hydrolysates. It is proposed that these
      acidophilic actinomycetes be assigned to a new genus, Streptacidiphilus gen.
      nov., on the basis of genotypic and phenotypic differences. Three species were
      defined on the basis of DNA:DNA pairing and phenotypic data, namely,
      Streptacidiphilus albus sp. nov., the type species, Streptacidiphilus
      neutrinimicus sp. nov. and Streptacidiphilus carbonis sp. nov. Members of the
      genera Kitasatospora, Streptacidiphilus and Streptomyces share a number of key
      characteristics and form a stable monophyletic branch in the 16S rDNA tree. It
      is, therefore, proposed that the description of the family Streptomycetaceae be
      emended to account for properties shown by Kitasatospora and Streptacidiphilus
      species.

PMID- 12785305
TI  - Identification of lactic acid bacteria isolated from human vaginal secretions.
AB  - A total of 57 lactic acid bacteria were isolated from the vaginal secretions of
      259 patients. Of these strains, 37 were isolated from patients attending pre
      natal clinics and the remaining strains from patients attending post-natal
      clinics. The strains were identified by using simple physiological and
      biochemical tests and their phenotypic relatedness determined by numerical
      analysis of total soluble cell protein patterns. The genotypic relatedness of
      representative strains selected from each of the protein profile clusters was
      determined by numerical analysis of the DNA banding patterns obtained from RAPD
      PCR. The majority of lactobacilli isolated belonged to the species Lactobacillus
      pentosus, Lactobacillus fermentum and Enterococcus faecium. A few strains of
      Lactobacillus plantarum and Weissella viridescens were also isolated. One strain,
      TV 1029, grouped into the same protein profile cluster as E. faecium, but
      revealed a DNA banding pattern closer related to Enterococcus faecalis. This is
      the first report of W. viridescens associated with the human vagina.

PMID- 12785306
TI  - Comparison of 16S rDNA analysis and rep-PCR genomic fingerprinting for molecular
      identification of Yersinia pseudotuberculosis.
AB  - 16S rDNA sequence analysis and repetitive element sequence-based PCR (rep-PCR)
      genomic fingerprinting were evaluated on 11 type strains of the genus Yersinia
      and 17 recognized serotype strains of Y. pseudotuberculosis to investigate their
      genetic relatedness and to establish the value of techniques for the
      identification of Y. pseudotuberculosis. A phylogenetic tree constructed from 16S
      rDNA sequences showed that the type strains of Yersinia species formed distinct
      clusters with the exception of Y. pestis and Y. pseudotuberculosis. Moreover, Y.
      pestis NCTC 5923T was found to be closely related to Y. pseudotuberculosis
      serotypes 1b, 3, and 7. Dendrograms generated from REP-PCR, and ERIC-PCR data
      revealed that members of the genus Yersinia differed from each other with the
      degree of similarity 62% and 58%, respectively. However, the BOX-PCR results
      showed that Y. pestis 5923T clustered with the Y. pseudotuberculosis group with a
      degree of similarity 74%. According to these findings, 16S rDNA sequence analysis
      was unable to reliably discriminate Y. pseudotuberculosis from Y. pestis.
      However, REP-PCR and especially ERIC-PCR provided an effective means of
      differentiating between members of the taxa.

PMID- 12785307
TI  - Promicromonospora pachnodae sp. nov., a member of the (hemi)cellulolytic hindgut
      flora of larvae of the scarab beetle Pachnoda marginata.
AB  - Intestinal microorganisms play an important role in plant fiber degradation by
      larvae of the rose chafer Pachnoda marginata. In the hindgut of the larvae 2.5 to
      7.4 x 10(8) bacteria per ml of gut content with xylanase or endoglucanase
      activity were found. Bacteria in the midgut were not (hemi)cellulolytic, but the
      alkaline environment in this part of the intestinal tract functions as a
      precellulolytic phase, solubilizing part of the lignocellulosic material.
      Accordingly, the degradation of lignocellulose-rich material in Pachnoda
      marginata larvae appeared to be a combination of a physico-chemical and
      microbiological process. A number of different facultative anaerobic and strictly
      anaerobic bacteria with (hemi)cellulolytic activity were isolated from the
      hindgut. A dominant (hemi)cellulolytic species was a Gram positive, irregular
      shaped, facultative aerobic bacterium. Further physiological identification
      placed the isolate in the genus Promicromonospora. Comparative 16S rDNA analysis
      and phenotypic features revealed that the isolate represented a new species for
      which the name Promicromonospora pachnodae is proposed. P. pachnodae produced
      xylanases and endoglucanases on several plant derived polymers, both under
      aerobic and anaerobic conditions.

PMID- 12785308
TI  - Yeasts present during spontaneous fermentation of Lake Erie Chardonnay, Pinot
      Gris and Riesling.
AB  - The composition of wine yeast populations, present during spontaneous
      fermentation of Chardonnay, Pinot Gris and Riesling from the Lake Erie Region was
      studied. A combination of biochemical and molecular techniques was used to
      identify non-Saccharomyces and Saccharomyces yeast isolates. The biochemical
      techniques included analysis of yeast isolates by sugar fermentation and carbon
      and nitrogen assimilation. Molecular techniques involved ribotyping of a highly
      variable segment in the 26S rRNA gene using DNA sequence analysis and restriction
      fragment length polymorphism of amplified DNA. The results show that of the non
      Saccharomyces yeasts, several related species of Hanseniaspora, were the most
      abundant yeasts present during early stages of fermentation. Later in
      fermentation S. cerevisiae dominated, and based on biochemical analyses consisted
      of a heterogeneous group of genotypes. There were no major differences in yeast
      populations among the three types of juice analyzed.

PMID- 12785309
TI  - Differentiation of six sibling species in the Saccharomyces sensu stricto complex
      by multilocus enzyme electrophoresis and UP-PCR analysis.
AB  - UP-PCR analysis and multilocus enzyme electrophoresis were used to characterize
      37 strains of the sibling species Saccharomyces cerevisiae, S. bayanus, S.
      cariocanus, S. kudriavzevii, S. mikatae and S. paradoxus. The results demonstrate
      that both molecular approaches are useful for discriminating between these
      phenotypically indistinguishable Saccharomyces species. The data obtained are in
      excellent agreement with previously reported genetic analyses, sequencing of the
      18S rRNA and ITS regions, and DNA-DNA reassociation data.

PMID- 12785310
TI  - Cryptococcus haglerorum, sp. nov., an anamorphic basidiomycetous yeast isolated
      from nests of the leaf-cutting ant Atta sexdens.
AB  - A yeast strain (CBS 8902) was isolated from the nest of a leaf-cutting ant and
      was shown to be related to Cryptococcus humicola. Sequencing of the D1/D2 region
      of the 26S ribosomal DNA and physiological characterization revealed a separate
      taxonomic position. A novel species named Cryptococcus haglerorum is proposed to
      accommodate strain CBS 8902 that assimilates n-hexadecane and several benzene
      compounds. Physiological characteristics distinguishing the novel species from
      some other members of the C. humicola complex are presented. The phylogenetic
      relationship of these strains to species of the genus Trichosporon Behrend is
      discussed.

PMID- 12785311
TI  - Assessment of antimicrobial activity of hydrophilic betaines in osmotically
      stressed bacteria.
AB  - A series of hydrophilic aromatic and semi-aromatic betaines related to
      trigonelline was synthesized and tested for antimicrobial activity. 4
      Methylthiazolium betaine was the only one that showed significant antibacterial
      activity towards Escherichia coli under hyperosmotic conditions. None of the
      tested betaines showed any evidence of osmoprotection or urea protection.

PMID- 12785312
TI  - Characterization of an extracellular medium-chain-length poly(3-hydroxyalkanoate)
      depolymerase from Streptomyces sp. KJ-72.
AB  - A bacterial strain capable of degrading medium-chain-length polyhydroxyalkanoates
      (MCL-PHAs) was isolated from a soil sample. This organism, which was identified
      as Streptomyces sp. KJ-72, secreted MCL-PHA depolymerase into the culture fluid
      only when it was cultivated on MCL-PHAs. The extracellular MCL-PHA depolymerase
      of the organism was purified to electrophoretic homogeneity by ion exchange
      column chromatography and gel filtration. The enzyme consisted of a monomeric
      subunit having a molecular mass of 27.1 kDa and isoelectric point of 4.7. The
      maximum activity was observed at pH 8.7 and 50 degrees C. The enzyme was
      sensitive to N-bromosuccinimide and acetic anhydride, indicating the presence of
      tryptophan and lysine residues in the catalytic domain. The enzyme was able to
      hydrolyze various chain-length p-nitrophenyl esters of fatty acids and
      polycaprolactone as well as various types of MCL-PHAs. However, lipase activity
      of the enzyme was not detected. The main hydrolysis product of poly(3
      hydroxyheptanoate) was identified to be the dimer of 3-hydroxyheptanoate.

PMID- 12785314
TI  - [Spectroscopic and chromatographic studies on photochemical isomerism of alpha,
      beta-diunsaturated ketones].
AB  - Spectroscopic (UV, IR, NMR, MS) and chromatographic (HPLC, GC) investigations
      show for alpha,beta-diunsaturated ketones with one double bond fixed in a
      cyclohexene-, furan- or thiophene ring in most examples a photochemical Z/E
      isomerization in solution by the influence of light. Investigations of conformers
      by IR and NMR however are not influenced during usual operations and light
      protection is not nessessary.

PMID- 12785313
TI  - Mycotoxin production and evolutionary relationships among species of Aspergillus
      section Clavati.
AB  - Aspergillus clavatus is a commonly encountered fungus in the environment,
      producing a number of mycotoxins including patulin, kojic acid, cytochalasins and
      tremorgenic mycotoxins. A. clavatus belongs to Aspergillus section Clavati
      together with six other species, all of which possess clavate-shaped vesicles.
      Patulin production was analysed by thin layer chromatography and high performance
      liquid chromatography, while a primer pair developed for the detection of an iso
      epoxydon dehydrogenase gene involved in the biosynthesis of patulin in penicillia
      was used to detect the ability of patulin production in the isolates examined. A
      good correlation was observed between patulin producing properties, and the
      presence of an iso-epoxydon dehydrogenase gene fragment among the isolates
      tested. A. longivesica was found for the first time to produce patulin. Ribotoxin
      production was also examined using a PCR-based approach. Ribotoxins were detected
      for the first time in an A. pallidus and a Hemicarpenteles acanthosporus isolate.
      A phylogenetic analysis of intergenic transcribed spacer sequence data indicated
      that most isolates belong to two main clades that have also been identified
      earlier based on 26 S rDNA sequence data. A. pallidus isolates clustered together
      with A. clavatus strains. Although A. clavatus isolates produced highly
      homogeneous random amplified polymorphic DNA profiles, phylogenetic analysis of
      these data let us cluster A. clavatus isolates into distinct clades. Correlations
      were not observed between either patulin or ribotoxin production, and the
      taxonomic position of the isolates tested, indicating that patulin and ribotoxin
      producing abilities were lost several times during evolution of Aspergillus
      section Clavati. Although patulin was earlier found to inhibit mycovirus
      replication, one of the mycovirus carrying isolates also produced patulin, and
      both carried the iso-epoxydon dehydrogenase gene.

PMID- 12785315
TI  - [Photometric determination of iron contamination of drugs and biological
      matrices].
AB  - The Ph. Eur. detects colorimetrically the limiting value of iron by formation of
      a complex with thioglycolic acid in ammoniacal solution. This reaction was
      rechecked by experiments. Contrary to the literature a solvated Fe(II)-complex
      will be formed due to the reduction of Fe(III) by the present thioglycolic acid.
      A supposed oxidation of the Fe(II)-complex by atmospheric oxygen does not occur.
      For the routine determination of traces of iron in medicinal substances and
      biological matrixes a VIS-method was developed based on the measurement of the
      absorption of the complex at 534 nm in the range of 10-100 ppm after graded
      oxidative decomposition with conc. sulfuric acid/H2O2 30%. This assay needs a
      calibration mixture or in the case of a higher demand of accuracy a calibration
      curve with at least five measuring points. Because of the contamination of
      commercially available reagents a blank value must be determined.

PMID- 12785317
TI  - Identifying the vulnerable plaque.

PMID- 12785316
TI  - Aggressive treatment of atherosclerosis: the time is now.
AB  - In patients with known cardiovascular disease and those at high risk for it,
      physicians must begin to treat atherosclerosis earlier, with combination therapy
      of statins, aspirin, angiotensin-converting enzyme inhibitors, and beta-blockers.
      In those hospitalized with a cardiovascular event, a statin should be started in
      the hospital, regardless of lipid levels. Patients with diabetes should be
      treated as if they have preexisting cardiovascular disease.

PMID- 12785318
TI  - Constructing experience in individual interview, autobiographies and on-line
      accounts: a poststructuralist approach.

PMID- 12785319
TI  - The effect of induced muscle tension and fatigue on the oculocardiac reflex.
AB  - INTRODUCTION: We investigated surgeon-modified factors in the oculocardiac reflex
      (OCR) including repeating tension after return to baseline pulse (fatigue) or
      modifying the tension place on the extraocular muscle (EOM). METHODS: A control
      group of 842 adult and pediatric strabismus cases underwent controlled, 200 gram,
      10-second square wave tension on at least two EOM. The effect of TENSION was
      studied in 90 random cases by placing a tension of 50 grams on one of the later
      muscles and a tension of 400 grams on another subsequent muscle. The effect of
      FATIGUE was studied in 30 cases when the initial tension elicited a profound
      bradycardia. The heart rate was allowed to return to within 96% of pre-tension
      levels, and the same muscle had a second identical tension. RESULTS: For the 842
      control cases, aged 12 +/- 16 (s.d.) years, initial 200 gram OCR was -16.9 +/-
      19% and the second muscle 15 +/- 7 minutes later was significantly less percent
      change -14.6+/- 17%, paired t=3.9, p= .0001. TENSION: OCR was a similar reduction
      of 16-18% for 200 gram and 400 gram tension but had a modest reduction of 10% for
      50 gram EOM tension. FATIGUE: For cases with profound initial OCR, waiting 3
      minutes produced only a 17% reduction in OCR severity. CONCLUSION: A surgeon can
      reduce oculocardiac reflex by exerting very gentle 50 gram tension on the EOM or
      waiting for return to baseline heart rate before fatiguing the reflex. These
      reductions are of less clinical value than pharmacologic intervention.

PMID- 12785320
TI  - Strabology Report of the 29th Annual Meeting of the American Association for
      Pediatric Ophthalmology and Strabismus. The Hilton Waikoloa Village, Waikoloa,
      Hawaii, March 23-27, 2003.

PMID- 12785321
TI  - [The legal regulations for prevention and treatment of occupational diseases in
      P.R.C---the "Care god" of labourers and the "Patron saint" of enterprises].

PMID- 12785322
TI  - Immigration and immigration research in the United States.

PMID- 12785323
TI  - Haplotypes, "hyplotypes," and complex genetic disease.

PMID- 12785324
TI  - [Current status fro management of oral and maxillofacial neoplasm in China].

PMID- 12785325
TI  - [Johann Theodor Eller, a famous 18th century German physician and scientist].

PMID- 12785326
TI  - [What radiologist want to radiographers in the room of angiography].

PMID- 12785327
TI  - [The up-to-date vascular imaging technology using multislice CT].

PMID- 12785328
TI  - [The latest technology and application technology of vascular delineation in
      MRI].

PMID- 12785329
TI  - [The leading edge and usefulness of the circumferential technology for IVR].

PMID- 12785330
TI  - Rescue therapy with tacrolimus in a patient with toxic megacolon.
AB  - BACKGROUND: Toxic megacolon is a life-threatening complication most commonly
      observed in patients with ulcerative colitis or Crohn's disease that is
      characterized by total or segmental nonobstructive colonic dilatation of at least
      6 cm on plain abdominal films associated with systemic toxicity. CASE REPORT: We
      report an unusual case of fulminant steroid-refractory ulcerative colitis
      complicated by toxic megacolon treated successfully with the immunosuppressant
      tacrolimus. CONCLUSION: Tacrolimus administration induced clinical remission and
      bridged the time interval, until the standard immunosuppressant azathioprine
      could maintain clinical remission, thereby avoiding eminent emergency colectomy.

PMID- 12785331
TI  - Adenocarcinoma of the ileoanal pouch anastomosis: an emerging complication?
AB  - BACKGROUND AND AIMS: Restorative proctocolectomy with ileoanal pouch anastomosis
      (IPAA) is currently the surgical treatment of choice for ulcerative colitis.
      Although dysplastic changes to the native ileal mucosa of the pouch occur in a
      subgroup of patients with severe chronic pouchitis, the development of cancer in
      the pouch itself is a very rare event. To date, only two cases of carcinoma of
      the IPAA have been reported, namely in patients operated on for colon cancer
      complicating ulcerative colitis and with a previous diagnosis of backwash
      ileitis. CASE REPORT: We report a patient with carcinoma in an ileoanal pouch who
      had been suffering from chronic atrophic pouchitis early after surgery. He had no
      previous history of colon cancer or backwash ileitis. The adenocarcinoma was
      detected 22 months after IPAA, and it was deeply infiltrating the adjacent
      structures (pT4N0M0, grade 2). Histology revealed the passage from chronic
      atrophic pouchitis to dysplastic epithelium and to cancer. CONCLUSION: Our case
      suggests that malignant transformation of the IPAA may occur as a pure
      complication of the severe chronic pouchitis, even in the absence of backwash
      ileitis or a previous history of colon cancer.

PMID- 12785332
TI  - Induced abortion: an ethical conundrum for counselors.
AB  - Induced abortion is one of the most controversial moral issues in American
      culture, but counselor value struggles regarding abortion are seldom addressed in
      counseling literature. This article considers the conflictual nature of the the
      ethical principles of autonomy, fidelity, justice, beneficence, and
      nonmaleficence as they can occur within the context of the counseling
      relationship, particularly with clients considering abortion. In addition, the
      authors present strategies for counselor self-evaluation, offer recommendations,
      and provide questions to facilitate ethical decision making.

PMID- 12785333
TI  - The crisis of confidentiality in the control of the HIV/AIDS pandemic in
      Botswana.

PMID- 12785334
TI  - Care of elders in the community: moral lives, moral quandaries.

PMID- 12785336
TI  - Old ethical frameworks: what works, what doesn't?

PMID- 12785337
TI  - An ethic of care.

PMID- 12785338
TI  - [Biographies of 20th century Polish medical scientists].

PMID- 12785339
TI  - [The medical schools ethic commitment to their students ].

PMID- 12785340
TI  - The science and ethics of long-term care.

PMID- 12785341
TI  - Creating an ethical organization.

PMID- 12785342
TI  - Cross-cultural geriatric ethics: negotiating our differences.

PMID- 12785343
TI  - Addressing prejudice: the effects of ethical perspectives.

PMID- 12785344
TI  - Ethics and the frontline long-term care worker: a challenge for the 21st century.

PMID- 12785345
TI  - Care at home: virtue in multigenerational households.

PMID- 12785346
TI  - Who's safe? Who's sorry? The duty to protect the safety of clients in home- and
      community-based care.

PMID- 12785348
TI  - Balancing autonomy and resources in healthcare for elders.

PMID- 12785347
TI  - Ethics in clinical practice with older adults: recognizing biases and respecting
      boundaries.

PMID- 12785349
TI  - Transcatheter closure of atrial septal defects.
AB  - Until recently, surgical repair was the standard treatment for an ostium secundum
      atrial septal defect (ASD), a common congenital heart defect. Closing ASDs using
      a device inserted via a catheter now offers another option for some patients.
      Limited comparative data indicate that newer approaches to transcatheter repair
      have a higher failure rate than that for surgery, but short-term complication
      rates are lower. Evidence from long-term follow-up of patients with device
      closure of ASDs is not yet available. Equipment and procedure costs may be higher
      for transcatheter closure than for surgery, but overall costs may be reduced
      through avoiding intensive care unit costs and through shorter hospital stays.

PMID- 12785350
TI  - Drug assistance from drug makers.
AB  - Although money problems are limiting the development of new, large scale, state
      pharmaceutical assistance programs, some legislators are finding out what can be
      done at little of no state expense

PMID- 12785357
TI  - The need for independent physics advice.

PMID- 12785363
TI  - Plugging the leak--benefits of the vasopressin-2 agonist, desmopressin in
      autonomic failure.

PMID- 12785366
TI  - A stand in favor of financial incentives in organ recovery.

PMID- 12785367
TI  - Medical ethics in a litigious climate.

PMID- 12785368
TI  - A tour of bioethics: where does the mind fit in?

PMID- 12785369
TI  - Moral development and bioethics.

PMID- 12785370
TI  - What psychiatry can offer ethics: psychodynamic contributions.

PMID- 12785372
TI  - The economics of big game hunting: using a rifle to get a clear shot
      transplantation.

PMID- 12785371
TI  - Donor complications and outcomes in live-liver transplantation.

PMID- 12785373
TI  - Sanctity, secrecy, and silence: dilemmas in clinical confidentiality.

PMID- 12785374
TI  - Can controlled non-heart-beating donors provide a solution to the organ shortage?

PMID- 12785375
TI  - Advancing the ethics of research.

PMID- 12785376
TI  - Gratitude and coercion between physicians and patients.

PMID- 12785377
TI  - Steroid withdrawal after pediatric liver transplantation: a long-term follow-up
      study in 109 recipients.

PMID- 12785378
TI  - Placebo studies: lessons from psychiatric research.

PMID- 12785379
TI  - Skin protectant drug products for over-the-counter human use; final monograph.
      Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule in the form of a
      final monograph establishing conditions under which over-the-counter (OTC) skin
      protectant drug products are generally recognized as safe and effective and not
      misbranded as part of the ongoing review of OTC drug products conducted by FDA.
      The final monograph includes OTC skin protectant drug products for minor cuts,
      scrapes, burns, chapped skin and lips, poison ivy, poison oak, poison sumac, and
      insect bites. FDA is issuing this final rule after considering public comments on
      the agency's proposed regulation, which was issued in the form of a tentative
      final monograph, and all new data and information on skin protectant drug
      products for these specific uses that have come to the agency's attention. This
      final rule amends the regulation that lists nonmonograph active ingredients by
      adding those OTC skin protectant ingredients that have been found to be not
      generally recognized as safe and effective. This final rule also lifts the stay
      of 21 CFR part 352 (published at 66 FR 67485, December 31, 2001) to amend the
      final monograph for OTC sunscreen drug products to include sunscreen-skin
      protectant combination drug products, and then stays Sec. 347.20(d) (21 CFR
      347.20(d)) and part 352 until further notice in the Federal Register.

PMID- 12785400
TI  - Cost-effectiveness of perirectal surveillance cultures for controlling vancomycin
      resistant Enterococcus.

PMID- 12785401
TI  - Nosocomial outbreak of Serratia marcescens in a neonatal intensive care unit.

PMID- 12785402
TI  - Control of nosocomial methicillin-resistant Staphylococcus aureus: where shall we
      send our hospital director next time?

PMID- 12785403
TI  - An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal
      intensive care unit.
AB  - OBJECTIVE: To describe the epidemiologic and molecular investigations that
      successfully contained an outbreak of methicillin-resistant Staphylococcus aureus
      (MRSA) in a neonatal intensive care unit (NICU). DESIGN: Isolates of MRSA were
      typed by pulsed-field gel electrophoresis (PFGE) and S. aureus protein A (spa).
      SETTING: A level III-IV, 45-bed NICU located in a children's hospital within a
      medical center. PATIENTS: Incident cases had MRSA isolated from clinical cultures
      (eg, blood) or surveillance cultures (ie, anterior nares). INTERVENTIONS:
      Infected and colonized infants were placed on contact precautions, cohorted, and
      treated with mupirocin. Surveillance cultures were performed for healthcare
      workers (HCWs). Colonized HCWs were treated with topical mupirocin and
      hexachlorophene showers. RESULTS: From January to March 2001, the outbreak strain
      of MRSA, PFGE clone B, was harbored by 13 infants. Three (1.3%) of 235 HCWs were
      colonized with MRSA. Two HCWs, who rotated between the adult and the pediatric
      facility, harbored clone C. One HCW, who exclusively worked in the children's
      hospital, was colonized with clone B. From January 1999 to November 2000, 22
      patients hospitalized in the adult facility were infected or colonized with clone
      B. Spa typing and PFGE yielded concordant results. PFGE clone B was identified as
      spa type 16, associated with outbreaks in Brazil and Hungary. CONCLUSIONS: A
      possible route of MRSA transmission was elucidated by molecular typing. MRSA
      appears to have been transferred from our adult facility to our pediatric
      facility by a rotating HCW. Spa typing allowed comparison of our institution's
      MRSA strains with previously characterized outbreak clones.

PMID- 12785404
TI  - Acquisition of methicillin-resistant Staphylococcus aureus in a large intensive
      care unit.
AB  - OBJECTIVES: To determine the prevalence of MRSA colonization on admission to the
      ICU and the incidence of MRSA colonization in the ICU. DESIGN: Prospective cohort
      study. SETTING: University hospital. PARTICIPANTS: Patients admitted to the ICU
      in 2000-2001. METHODS: Patients were screened for MRSA with nose, throat, groin,
      and axilla swabs on admission and discharge. MRSA acquisition was defined as a
      negative admission screen and a positive discharge screen. Risk factors analyzed
      included previous wards/current unit, gender, age, and length of stay prior to
      and in the ICU. Univariate and multivariate analyses were performed using
      logistic regression. RESULTS: Of screened patients, 6.8% were MRSA colonized on
      admission to the ICU. Some patients (11.4%) became newly colonized during their
      stay in the ICU. Factors that remained significant in the multivariate analysis
      of MRSA colonization on admission were previous admission to various wards and
      length of stay prior to ICU admission of more than 3 days. In the multivariate
      analysis of MRSA acquisition in the ICU, being a trauma patient and length of
      stay in the ICU greater than 2 days remained significant Thirty-six percent of
      patients had both admission and discharge swabs taken. This percentage increased
      in the presence of a supervisory nurse. CONCLUSION: Significant acquisition of
      MRSA occurs in the ICU of our hospital, with trauma patients at increased risk.
      Patients who had been on the cardiothoracic ward prior to the ICU had a lower
      risk of MRSA colonization on admission. Presence of a supervisory nurse improved
      compliance with screening

PMID- 12785405
TI  - Predictive value and cost-effectiveness analysis of a rapid polymerase chain
      reaction for preoperative detection of nasal carriage of Staphylococcus aureus.
AB  - OBJECTIVE: To determine the accuracy and cost-effectiveness of a polymerase chain
      reaction (PCR) for detecting nasal carriage of Staphylococcus aureus directly
      from clinical specimens. CROSS-SECTIONAL STUDY: This occurred in a tertiary-care
      hospital in Cleveland, Ohio, and included 239 consecutive patients who were
      scheduled for a cardiothoracic surgical procedure. Conventional cultures and a
      PCR for S. aureus from nasal swabs were used as measurements. COST-EFFECTIVENESS
      ANALYSIS: Data sources were market prices and Bureau of Labor Statistics. The
      time horizon was the maximum period for availability of culture results (3 days).
      Interventions included universal mupirocin therapy without testing; initial
      therapy, with termination if PCR negative (treat-PCR); initial therapy, with
      termination if culture negative (treat-culture); treat PCR-positive carriers (PCR
      guided treatment); and treat culture-positive carriers (culture-guided
      treatment). The perspective was institutional and costs and the length of time to
      treatment were outcome measures. RESULTS: Sixty-seven (28%) of the 239 swabs grew
      S. aureus. Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of
      S. aureus. For populations with prevalences of nasal S. aureus carriage of up to
      50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided
      treatment had the lowest incremental cost-effectiveness ratio (1.93 dollars per
      additional day compared with the culture strategy). Among immediate treatment
      strategies, treat-PCR was most cost-effective. The universal therapy strategy
      cost 38.19 dollars more per additional day gained with carrier identification
      compared with the PCR strategy. CONCLUSION: Rapid real-time PCR is an accurate,
      rapid, and cost-effective method for identifying S. aureus carriers for
      preoperative intervention.

PMID- 12785406
TI  - Are there regional variations in the diagnosis, surveillance, and control of
      methicillin-resistant Staphylococcus aureus?
AB  - OBJECTIVE: To assess the way healthcare facilities (HCFs) diagnose, survey, and
      control methicillin-resistant Staphylococcus aureus (MRSA). DESIGN:
      Questionnaire. SETTING: Ninety HCFs in 30 countries. RESULTS: Evaluation of
      susceptibility testing methods showed that 8 laboratories (9%) used oxacillin
      disks with antimicrobial content different from the one recommended, 12 (13%) did
      not determine MRSA susceptibility to vancomycin, and 4 (4.5%) reported instances
      of isolation of vancomycin-resistant S. aureus but neither confirmed this
      resistance nor alerted public health authorities. A MRSA control program was
      reported by 55 (61.1%) of the HCFs. The following isolation precautions were
      routinely used: hospitalization in a private room (34.4%), wearing of gloves
      (62.2%), wearing of gowns (44.4%), hand washing by healthcare workers (53.3%),
      use of an isolation sign on the patient's door (43%), or all four. When the
      characteristics of HCFs with low incidence rates (< 0.4 per 1,000 patient-days)
      were compared with those of HCFs with high incidence rates (> or = 0.4 per 1,000
      patient-days), having a higher mean number of beds per infection control nurse
      was the only factor significantly associated with HCFs with high incidence rates
      (834 vs 318 beds; P = .02). CONCLUSION: Our results emphasize the urgent need to
      strengthen the microbiologic and epidemiologic capacities of HCFs worldwide to
      prevent MRSA transmission and to prepare them to address the possible emergence
      of vancomycin-resistant S. aureus.

PMID- 12785407
TI  - Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin
      remain effective?
AB  - OBJECTIVE: To determine the efficacy of mupirocin ointment in reducing nasal
      colonization with mupirocin-susceptible, methicillin-resistant Staphylococcus
      aureus (MS MRSA) as well as mupirocin-resistant MRSA (MR MRSA). DESIGN:
      Prospective evaluation in which patients colonized with MRSA were treated twice
      daily with 2% topical mupirocin ointment for 5 days. SETTING: James H. Quillen
      Veterans' Affairs Medical Center. PATIENTS: Forty hospitalized patients with two
      anterior nares cultures positive for MRSA within a 7-day period. METHODS: Treated
      patients had post-treatment cultures at day 3 and weeks 1, 2, and 4. Isolates
      underwent mupirocin-susceptibility testing and DNA typing. MRSA clearance and
      type turnover were assessed for isolates that were mupirocin-susceptible, low
      level (LL) MR MRSA and high-level (HL) MR MRSA. RESULTS: Post-treatment nares
      cultures on day 3 were negative for 78.5%, 80%, and 27.7% of patients with MS
      MRSA, LL-MR MRSA, and HLMR MRSA, respectively. Sustained culture negativity at 1
      to 4 weeks was more common in the MS MRSA group (91%) than in the LL-MR MRSA
      group (25%) or the HL-MR MRSA group (25%). Positive post-treatment cultures
      usually showed the same DNA pattern relative to baseline. Plasmid curing of 18 HL
      MR MRSA resulted in 15 MS MRSA and 3 LL-MR MRSA. CONCLUSIONS: Mupirocin was
      effective in eradicating MS MRSA, but strains of MR MRSA often persisted after
      treatment. This appeared to reflect treatment failure rather than exogenous
      recolonization. MR MRSA is now more prevalent and it is appropriate to sample
      MRSA populations for mupirocin susceptibility prior to incorporating mupirocin
      into infection control programs.

PMID- 12785408
TI  - A prospective observational study of the effect of penicillin skin testing on
      antibiotic use in the intensive care unit.
AB  - BACKGROUND: Patients with penicillin allergy admitted to the intensive care unit
      (ICU) frequently receive non-beta-lactam antimicrobials for the treatment of
      infection. The use of these antimicrobials, more commonly vancomycin and
      fluoroquinolones, is associated with the emergence of multidrug-resistant
      infections. The penicillin skin test (PST) can help detect patients at risk of
      developing an immediate allergic reaction to penicillin and those patients with a
      negative PST may be able to use a penicillin antibiotic safely. METHODS: We
      determined the incidence of true penicillin allergy, the percentage of patients
      changed to a beta-lactam antimicrobial when the test was negative, the safety of
      the test, and the safety of administration of beta-lactam antimicrobials in
      patients with a negative test. Skin testing was performed using standard
      methodology. RESULTS: One hundred patients admitted to 4 ICUs were prospectively
      studied; 58 of them were male. The mean age was 63 years. Ninety-six patients had
      the PST: one was positive (1.04%), 10 (10.4%) were nondiagnostic, and 85 (88.5%)
      were negative. Of the 38 patients who received antimicrobials for therapeutic
      reasons, 31(81.5%) had the antibiotic changed to a beta-lactam antimicrobial
      after a negative reading versus 7 patients of the 57 (12%) who had received a
      prophylactic antimicrobial (P < .001). No adverse effects were reported after the
      PST or after antimicrobial administration. CONCLUSIONS: The PST is a safe,
      reliable, and effective strategy to reduce the use of non-beta-lactam
      antimicrobials in patients who are labeled as penicillin allergic and admitted to
      the ICU.

PMID- 12785409
TI  - Impact of antibiotic-resistant pathogens colonizing the respiratory secretions of
      patients in an extended-care area of the emergency department.
AB  - OBJECTIVE: To determine the incidence of acquired infection, and the incidence,
      risk factors, and molecular typing of multidrug-resistant bacterial organisms
      (MROs) colonizing respiratory secretions or the oropharynx of patients in an
      extended-care area of the emergency department (ED) in a tertiary-care university
      hospital. METHODS: A case-control study was conducted regarding risk factors for
      colonization with MROs in ED patients from July 1996 to August 1998. The most
      prevalent MRO strains were determined using plasmid and genomic analysis with
      PFGE. RESULTS: MROs colonized 59 (25.4%) of 232 ED patients and 173 controls. The
      mean ED length of stay for the 59 cases was 13.9 days versus 9.8 days for the 173
      controls. The mean length of stay prior to the first isolation of MROs was 9.9
      days. MRO species included Acinetobacter baumannii, Staphylococcus aureus, and
      Pseudomonas aeruginosa. The rate of hospital-acquired infection was 32.7 per
      1,000 ED patient-days. The case fatality rate was significantly higher for cases.
      Univariate analysis identified mechanical ventilation, nebulization, nasogastric
      intubation, urinary catheterization, antibiotic therapy, and number of
      antibiotics as risk factors for MRO colonization. Multivariate regression
      analysis found that mechanical ventilation and nasogastric intubation
      independently predicted MRO colonization. Endemic clones were identified by PFGE
      in ED patients and were also found in patients in other parts of the hospital.
      CONCLUSIONS: Prolonged stay in the ED posed a risk for colonization with MROs and
      for contracting nosocomial infections, both of which were associated with
      increased mortality. Patients colonized with antibiotic-resistant A. baumannii
      may serve as a reservoir for spread in this hospital.

PMID- 12785410
TI  - Antimicrobial proficiency testing of National Nosocomial Infections Surveillance
      System hospital laboratories.
AB  - OBJECTIVE: The National Nosocomial Infections Surveillance (NNIS) System
      personnel report trends in antimicrobial-resistant pathogens. To validate select
      antimicrobial susceptibility testing results and to identify test methods that
      tend to produce errors, we conducted proficiency testing among NNIS System
      hospital laboratories. SETTING: NNIS System hospital laboratories in the United
      States. METHODS: Each laboratory received five organisms (ie, an imipenem
      resistant Serratia marcescens, an oxacillin-resistant Staphylococcus aureus, a
      vancomycin-resistant Enterococcus faecalis, a vancomycin-intermediate
      Staphylococcus epidermidis, and an extended-spectrum beta-lactamase (ESbetaL)
      producing Klebsiella pneumoniae). Testing results were compared with reference
      testing results from the Centers for Disease Control and Prevention. RESULTS: Of
      138 laboratories testing imipenem against the Serratia marcescens strain, 110
      (80%) correctly reported minimum inhibitory concentrations (MICs) or zone sizes
      in the resistant range. All 193 participating laboratories correctly reported the
      Staphylococcus aureus strain as oxacillin resistant Of the 193 laboratories, 169
      (88%) reported correct MICs or zone sizes for the vancomycin-resistant
      Enterococcus faecalis. One hundred sixty-two (84%) of 193 laboratories
      demonstrated the ability to detect a vancomycin-intermediate strain of
      Staphylococcus epidermidis, however, disk diffusion performed poorly when testing
      both staphylococci and enterococci with vancomycin. Although laboratory personnel
      correctly reported nonsusceptible extended-spectrum cephalosporins and aztreonam
      results for K. pneumoniae, only 98 (51%) of 193 correctly reported this organism
      as an ESbetaL producer. CONCLUSION: Overall, NNIS System hospital laboratory
      personnel detected most emerging resistance patterns. Disk diffusion continues to
      be unreliable for vancomycin testing of staphylococci and must be used cautiously
      for enterococci. Further education on the processing of ESbetaL-producing
      organisms is warranted.

PMID- 12785411
TI  - SHEA guideline for preventing nosocomial transmission of multidrug-resistant
      strains of Staphylococcus aureus and enterococcus.
AB  - BACKGROUND: Infection control programs were created three decades ago to control
      antibiotic-resistant healthcare-associated infections, but there has been little
      evidence of control in most facilities. After long, steady increases of MRSA and
      VRE infections in NNIS System hospitals, the Society for Healthcare Epidemiology
      of America (SHEA) Board of Directors made reducing antibiotic-resistant
      infections a strategic SHEA goal in January 2000. After 2 more years without
      improvement, a SHEA task force was appointed to draft this evidence-based
      guideline on preventing nosocomial transmission of such pathogens, focusing on
      the two considered most out of control: MRSA and VRE. METHODS: Medline searches
      were conducted spanning 1966 to 2002. Pertinent abstracts of unpublished studies
      providing sufficient data were included. RESULTS: Frequent antibiotic therapy in
      healthcare settings provides a selective advantage for resistant flora, but
      patients with MRSA or VRE usually acquire it via spread. The CDC has long
      recommended contact precautions for patients colonized or infected with such
      pathogens. Most facilities have required this as policy, but have not actively
      identified colonized patients with surveillance cultures, leaving most colonized
      patients undetected and unisolated. Many studies have shown control of endemic
      and/or epidemic MRSA and VRE infections using surveillance cultures and contact
      precautions, demonstrating consistency of evidence, high strength of association,
      reversibility, a dose gradient, and specificity for control with this approach.
      Adjunctive control measures are also discussed. CONCLUSION: Active surveillance
      cultures are essential to identify the reservoir for spread of MRSA and VRE
      infections and make control possible using the CDC's long-recommended contact
      precautions.

PMID- 12785412
TI  - The global impact of systemic lupus erythematosus.

PMID- 12785413
TI  - Serum homocysteine concentrations and their relation to serum folate and vitamin
      B12 concentrations and coronary artery disease prevalence in an urban, bi-ethnic
      community.
AB  - OBJECTIVE: To compare fasting serum total homocysteine (tHcy) concentrations in a
      randomly selected sample of elderly (> or = 65 years of age) Hispanic and non
      Hispanic White (NHW) men and women, to examine associations of tHcy with folate
      and vitamin B12, and then to correlate these with the prevalence of coronary
      heart disease (CHD) in these 4 ethnic/ gender groups. DESIGN AND PARTICIPANTS:
      Equal numbers of Hispanic and NHW men and women were randomly selected from the
      Healthcare Financing Administration (Medicare) registrant list for Bernalillo
      County (Albuquerque), New Mexico, and asked to volunteer for a paid home
      interview, to be followed by a paid, comprehensive interview/examination covering
      health and health-related issues. INTERVENTIONS AND MAIN OUTCOME MEASURES: Serum
      concentrations of tHcy, folate, and vitamin B12 were determined and correlated
      with the prevalence of CHD, after adjusting for other CHD risk factors (age,
      diabetes, hypertension, smoking, dyslipidemia, adiposity). RESULTS: Men and
      Hispanics had higher serum tHcy concentrations compared to women and non-Hispanic
      Whites (NHWs), respectively. After adjusting for lower concentrations of serum
      folate and vitamin B12 in Hispanics, the differences between Hispanics and NHWs
      were no longer significant. There was a direct association between serum tHcy
      concentrations and the prevalence of CHD after adjusting for other known risk
      factors that was most significant in Hispanic women. CONCLUSIONS: The higher
      serum tHcy concentrations observed in Hispanics compared to NHWs can be explained
      by lower levels of serum folate and vitamin B12. A direct association between
      serum tHcy concentrations and prevalence of CHD was observed primarily in women,
      and was most significant in Hispanic women.

PMID- 12785414
TI  - A tyrosine hydroxylase microsatellite and hemodynamic response to stress in a
      multi-ethnic sample of youth.
AB  - OBJECTIVE: Behavioral stress is believed to have an impact on cardiovascular
      health. As the rate-limiting enzyme in the pathway for catecholamine synthesis,
      tyrosine hydroxylase is a candidate gene for variability in cardiovascular
      function. The aim of this study was to determine whether a relationship exists
      between a tyrosine hydroxylase microsatellite and resting hemodynamic function,
      and/or hemodynamic responsivity to laboratory stress. DESIGN: Subjects underwent
      2 laboratory stressors: a video game challenge and a social competence interview.
      SETTING: The stressors were administered in a laboratory setting. PARTICIPANTS:
      Subjects were 292 10- to 20-year-old normotensive African-American and European
      American twin pairs. MAIN OUTCOME MEASURES: Blood pressure (BP) and heart rate
      (HR) were measured at rest and in response to the stressors. RESULTS: Chi-square
      analyses using re-sampling to account for the twin design indicated that allele
      and genotype frequencies were significantly different between European Americans
      and African Americans (P < or = .0001). Analyses of variance indicated that the
      184 and 199 bp alleles were associated with an attenuation of the hemodynamic
      response to stress with increasing age (P < or = .003, P < or = .002,
      respectively), while the 188 bp allele was associated with a higher resting
      systolic blood pressure (SBP) (P < or = .02), and greater hemodynamic response to
      stress with increasing BMI (P < or = .02). CONCLUSIONS: This study showed that in
      a multi-ethnic sample of normotensive adolescents, specific alleles of this
      tyrosine hydroxylase microsatellite were associated with protective or
      deleterious cardiovascular effects with subjects at rest and responding to
      stress.

PMID- 12785415
TI  - Genetic and environmental influences on blood pressure and pulse pressure among
      adult African Americans.
AB  - OBJECTIVE: The purpose of the present study was to identify sources of
      variability for systolic blood pressure (SBP), diastolic blood pressure (DBP),
      and pulse pressure (PP) in a sample of adult African-American twins. DESIGN: The
      classic twin design was employed to examine genetic and environmental sources of
      variance in the outcome measures of interest. PARTICIPANTS: Participants were 143
      (71 MZ and 72 DZ) same-sex, intact twin pairs (mean age = 49.87 years; SD 13.62),
      who took part in the Carolina African-American Twin Study of Aging (CAATSA). MAIN
      OUTCOME MEASURES: Outcome measures of interest included SBP and DBP, and PP.
      RESULTS: For older twins, heritabilities were .52 for SBP, .36 for DBP, and .14
      for PP. However, for younger twins, heritabilities were .44 for SBP, .27 for DBP,
      but no genetic influence on PP was observed. CONCLUSION: The results indicate
      that genetic factors are a significant source of variance in hemodynamic indices,
      and also suggest that, with advancing age, genetic factors play an increasing
      role in determining blood pressure and PP in this population.

PMID- 12785416
TI  - Body image perceptions and dieting among African-American pre-adolescent girls
      and parents/caregivers.
AB  - This study describes body image and weight concern attitudes of pre-adolescent
      African-American (AA) girls and their parent/caregivers. Cross-sectional survey
      data were collected from 189 low-income 8- to 10-year-old AA girls and 179
      parents/caregivers of AA girls from 2 urban areas, Memphis and Minneapolis/St.
      Paul. Results demonstrated that most AA girls were either happy with their
      weight, or did not think about it at all. However, 20% of girls would like to be
      larger than their current size, and 50% would like to be smaller. Girls in
      Minneapolis/St. Paul were more likely than Memphis girls to report weight
      dissatisfaction. One third of parents reported concerns that their daughters were
      too heavy. Seventy-two percent of parents reported that they were trying to lose
      weight. Discussions include possible regional differences in weight concern among
      AA girls, and implications for obesity prevention programs.

PMID- 12785417
TI  - The Black Seventh-Day Adventist exploratory health study.
AB  - African Americans are at high risk for stroke and dementia. Modifications of
      lifestyle, however, might lower this risk. The Seventh-Day Adventist (SDA) Church
      encourages both spiritual adherence and a healthy lifestyle. Members are
      encouraged to exercise and are discouraged from smoking, drinking alcoholic or
      caffeinated beverages, or eating meat. The present study describes an exploratory
      project in 2 Black SDA congregations (N = 82) designed to characterize the
      lifestyle, dietary, and spiritual health habits of these congregations, and to
      test the feasibility of collecting such information in the Black SDA community at
      large. Three separate data collection methods are described and evaluated. Data
      demonstrate that the sample differs significantly from the African-American
      community at large in dietary, lifestyle, and spiritual health habits. The Black
      SDA community represents a unique opportunity to test the effects of diet,
      lifestyle, and spirituality on risk for stroke and dementia.

PMID- 12785418
TI  - Uncovering factors contributing to under-utilization of breast cancer screening
      by Chinese and Korean women living in the United States.
AB  - OBJECTIVE: This study investigated factors influencing breast cancer screening
      utilization by Chinese and Korean women, living in the United States, and
      examined similarities and differences between the 2 sub-populations. DESIGN:
      Population-based cross-sectional surveys were used for comparisons. METHODS: A
      random sample of 180 women (Chinese = 117, Korean = 63), aged 40 years and older,
      who resided in an urban county of Michigan participated in the mail survey.
      Existing English questionnaires were modified for cultural appropriateness,
      translated into Chinese and Korean, and pre-tested. Data analysis included
      descriptive statistics, testing differences between means/percentages, and
      logistic regression. RESULTS: The sample population, similar to the Asian
      American population in general, was composed predominantly of immigrants with
      varying socioeconomic and health status. Approximately 56% of the women had
      received mammograms in the past 2 years, about 21% lower than the statewide rate
      for Michigan. The logistic regression indicated that women's mammography use was
      significantly associated with their ability to speak English, availability of
      health insurance, and knowledge of mammography (P < .05). Similarities and
      differences between sampled Chinese and Korean women existed in terms of their
      socio-demographic characteristics and the factors influencing their use of breast
      cancer screening. CONCLUSIONS: Understanding minority women's cancer screening
      behavior has implications for designing appropriate interventions to meet their
      unique healthcare needs, thereby increasing screening rates and reducing
      mortality.

PMID- 12785419
TI  - Black-white differences in survival from late-stage prostate cancer.
AB  - OBJECTIVE: To examine differences between African Americans (Blacks) and non
      Hispanic Whites in risk of death after diagnosis of later-stage prostate cancer
      in a large sample of patients from US population-based cancer registries. The
      theory that Black patients with advanced cancer have a lower survival rate
      compared to their White counterparts, based on a single clinical trial, was
      tested with large samples of patients. METHODS: The Cox proportional hazards
      regression model was used to compare survival rates among 24,136 non-Hispanic
      White, and 3,817 Black prostate cancer patients diagnosed between 1988 and 1997,
      whose cancer had spread beyond the prostate capsule, and who resided in 9
      geographic areas covered by the National Cancer Institute's Surveillance,
      Epidemiology and End Results (SEER) Program of population-based cancer
      registries. Other analyses involved 5- and 10-year relative survival rates (RSRs)
      among non-Hispanic White and Black patients diagnosed with distant-stage prostate
      cancer from 1973 to 1994 (with almost all patients having had a chance to survive
      for at least 5 years). RESULTS: The risk of death from prostate cancer was only
      slightly higher for Blacks than for Whites (adjusted hazard rate ratio = 1.05),
      when age, extent of disease, tumor grade, marital status, and surgery were
      included in the Cox proportional hazards regression model. Five- and 10-year RSRs
      were about 2%-22% higher for Blacks and Whites in strata defined by extent of
      disease, or among patients with distant stage cancer, but differences were small
      among married patients. CONCLUSIONS: The findings do not indicate substantial
      Black-White differences in survival rates of later-stage prostate cancer
      patients, after adjusting for clinical characteristics and marital status.

PMID- 12785420
TI  - Tobacco use in a tri-ethnic population of older women in southeastern North
      Carolina.
AB  - OBJECTIVE: While many studies have evaluated the epidemiology of tobacco use
      nationally and among specific populations, less is known about the epidemiology
      of tobacco use among elderly women. We examined the epidemiology of tobacco use
      among a tri-racial population of elderly women in southeastern North Carolina.
      DESIGN: Survey SETTING: Senior centers, community events, and communal meal
      settings in Robeson County, North Carolina. PARTICIPANTS: Two hundred forty (240)
      women aged 60 and older, with approximately 80 women recruited from each ethnic
      group: Native American, African-American, and White. MAIN OUTCOME MEASURES:
      Demographic information, health history, and use of alcohol, cigarettes, and
      smokeless tobacco (ST). RESULTS: Of the total sample of 240 women, 38 (16%) were
      current ST users. In logistic regression analysis, current ST use was inversely
      associated with age and education, but positively associated with Native American
      or African-American ethnicity. Sixteen (17%) of the total sample were current
      smokers. In logistic regression, younger age and any alcohol use in the past year
      were associated with current smoking CONCLUSIONS: In a tri-ethnic, community
      based sample of older women, rates of current ST use were greater than national
      rates found among women of all ages in each ethnic group. On the other hand,
      rates of current smoking among these older women were lower than the national
      prevalence for women among all ages in these 3 respective ethnic groups. The
      distinctly different epidemiology of ST use vs cigarette smoking among these
      women high-lights the need to tailor tobacco interventions to each specific
      product.

PMID- 12785421
TI  - Family history, Hispanic ethnicity, and prostate cancer risk.
AB  - Family history is known to be a prostate cancer (CaP) risk factor for non
      Hispanic Whites (NHWs) and African Americans, but little data are available on
      the risk for Hispanics (Hs). This population-based case-control study used mailed
      surveys to assess the effects of ethnicity and family history of CaP on CaP risk
      in Hs and NHWs. Cases (N = 351) were those identified by the New Mexico Tumor
      Registry as having been newly diagnosed with CaP from October 1, 1994 to October
      31, 1995. Controls (N = 618) were randomly selected and frequency-matched to
      cases by ethnicity and 5-year age groups. Multivariate analyses were conducted
      using conditional logistic regression. After controlling for age, education, and
      income in the models, positive family history increased risk for both Hispanics
      (H) (OR 2.7, 95% CI 1.5-4.7) and non-Hispanic Whites (NHW) (OR 2.0, 95% CI 1.3
      3.1), suggesting that having a family history of CaP is a risk factor for both
      ethnic groups.

PMID- 12785423
TI  - Patient and practitioner literacy and women's health: a global view from the
      closing decade 1990-2000.
AB  - The health status of women is partly attributable to literacy. This paper
      presents an overview of 106 articles that include discussion of the relative
      impact of literacy on women's health worldwide. This synthesis reflects ways in
      which health status of women has been reported across ethnicity, age, formal
      education, cultural beliefs about health, access to healthcare information and
      services, and prevalence of various health conditions in different communities. A
      mother's knowledge and perception as a caretaker of her children's health, and
      the impact of the education and perception of the healthcare practitioner on his
      or her efficacy as conduits for women's health education will also be addressed.
      Models and recommendations are noted.

PMID- 12785422
TI  - A further study of life expectancy by socioeconomic factors in the National
      Longitudinal Mortality Study.
AB  - OBJECTIVES: The objective of this article is to provide estimates of life
      expectancy for White, Black, and Hispanic populations by socioeconomic factors.
      Effects of educational, income, employment, and marital status on life expectancy
      are presented and interpreted. DESIGN: The National Longitudinal Mortality Study,
      consisting of a number of Current Population Surveys (CPS) linked to mortality
      information obtained from the National Death Index, provides data to construct
      life tables for various socioeconomic and demographic groups. Probabilities of
      death are estimated using a person-year approach to accommodate the aging of the
      population over 11 years of follow up. RESULTS: Across various ethnicity-race-sex
      groups, longer life expectancy was observed for individuals with higher levels of
      education and income, and for those who were married and employed. The
      differences in life expectancy between levels of the socioeconomic
      characteristics tended to be larger for men than for women. Also, differences
      were found to be larger for the non-Hispanic Black population compared to the non
      Hispanic White population. Hispanic White men exhibited patterns similar to those
      of non-Hispanic White and Black men. CONCLUSIONS: For selected ethnicity-race-sex
      groups, the impact of socioeconomic variables on life expectancy is dramatic. The
      shorter life expectancy observed among the poor, the less educated, the
      unmarried, and those not in the labor force, highlights the impact of
      socioeconomic disadvantage on survival. Further, the substantial 14-year
      differential favoring the employed over those not in the labor force may be
      partially explained by unemployment due to poor health. Another reason may be
      that employed individuals have greater access to health care than do those not in
      the labor force.

PMID- 12785424
TI  - Patient preferences for physician characteristics in university-based primary
      care clinics.
AB  - OBJECTIVE: To examine patient preferences for age-,gender-, and racial/ethnic
      concordant primary care physicians. DESIGN: Focus group interviews. PATIENTS AND
      SETTING: Forty-nine adults (African Americans, Caucasians, and Latinos) receiving
      their outpatient medical care in university-based primary care clinics in
      Northern California. MAIN MEASURES AND RESULTS: Guiding questions were designed
      to elicit information about what patients look for in establishing and
      maintaining a therapeutic relationship with a primary care physician. Patients
      were prompted to provide examples and to discuss demographic-concordance factors.
      Many participants felt that their continuity of care was poor and that they could
      not choose their own primary care physicians in the academic system. Most
      reported tolerating these inconveniences for what they perceived to be a higher
      quality of care linked to medical innovations at academic medical centers.
      Patients' views regarding age concordance were varied and unrelated to gender or
      racial/ethnic group. Women in all English-proficient groups described gender
      concordance as important to their relationships with primary care physicians.
      Spanish-speaking participants uniformly preferred Spanish-speaking providers.
      African-American participants and Spanish-speaking Latino men felt that
      race/ethnic concordance contributed to a practitioner's empathy, and some were
      concerned by the lack of race/ethnic- or language-concordant doctors.
      CONCLUSIONS: Examining patients' preferences for patient-physician demographic
      concordance provides insight into the patient-physician relationship. Addressing
      areas where these preferences affect communication patterns and perceptions of
      quality of care may lead to overall improvements in patient-physician
      relationships and health outcomes.

PMID- 12785425
TI  - Retention of under-served women in clinical trials: a focus group study.
AB  - More information is needed to understand how women view their participation in
      clinical trials. As part of the formative evaluation phase of a 4-year National
      Cancer Institute funded study, researchers associated with the "Community
      Retention Intervention Study" (CRIS) conducted focus groups to identify
      additional data on the underlying issues regarding the retention and compliance
      of under-served women in clinical trials. Six focus groups were conducted: 3 were
      age-based, and 3 involved participants of the Women's Health Initiative (WHI)
      clinical trial component in Birmingham, Alabama. A total of 62 women, between 18
      and 87 years of age, participated in the sessions: 79% were African-American and
      52% reported incomes below dollar 20,000. The qualitative data analysis revealed
      that women were more inclined to participate in a clinical trial if they, or a
      family member, would benefit. Non-compliance with study protocols was generally a
      result of complications or unwanted side effects of treatments. Focus group data
      were used to develop retention and compliance strategies for the CRIS study.
      Findings suggest that focus group data can be used effectively to develop
      retention and compliance strategies specific to under-served women.

PMID- 12785426
TI  - A new model for developing and executing culturally appropriate behavior
      modification clinical trials for African Americans.
AB  - Past clinical trials addressing behavior modification for cardiovascular disease
      (CVD) prevention have not been culturally appropriate for African Americans. This
      supposition is borne out by the continued challenges researchers face not only in
      recruiting and retaining African Americans in clinical trials, but also in
      achieving the desired outcomes among this population. Investigators have limited
      resources to develop culturally appropriate CVD prevention trials. The scientific
      literature reveals 2 models for implementing culturally appropriate interventions
      applicable to CVD prevention among African Americans; however, these models are
      not easily applied to the clinical trial setting. We propose a new model for
      developing a culturally appropriate clinical trial. The clinical trial is a
      function of the investigator's cultural framework, meaning that an investigator
      will have more difficulty designing clinical trials appropriate for use with
      cultures other than his or her own, a definite limitation when attempting to
      effectively reach diverse populations. Differences between the cultural
      frameworks of most clinical trials and African Americans' cultural frameworks
      lead to intrinsic biases, limiting the ability of African Americans to achieve
      the desired outcomes for any particular trial. An African-American participant's
      degree of immersion in traditional African-American culture, or acculturation,
      influences the magnitude of these biases. Investigators must be aware of, and
      attempt to mitigate, such biases so that the trial's potential for success is
      equitable across ethnic groups. In addition, investigators must understand how to
      effectively address relevant biases of African Americans without challenging
      their ethnic identity. Steps to decrease biases are described.

PMID- 12785427
TI  - Effects of diet in lowering homocysteine levels and cardiovascular disease.

PMID- 12785428
TI  - The nature and nurture of blood pressure in African Americans.

PMID- 12785429
TI  - Mammography can detect breast cancer early and save women's lives.

PMID- 12785430
TI  - Survival rates of prostate cancer: black vs white patients.

PMID- 12785431
TI  - A further study of life expectancy by socioeconomic factors in the National
      Longitudinal Mortality Study.

PMID- 12785432
TI  - The impact of health knowledge and communication on women's health.

PMID- 12785433
TI  - What physician characteristics are important to patients?

PMID- 12785434
TI  - Focus group information helps researchers develop strategies to keep women in
      clinical trials.

PMID- 12785435
TI  - Medical liability crisis: an international problem.

PMID- 12785436
TI  - Complementary and alternative medicine use in families of children with cerebral
      palsy.
AB  - In order to assess patterns of usage of complementary and alternative medicine
      (CAM) in families of children with cerebral palsy (CP), 213 families with a child
      (0 to 18 years) with CP were recruited at the university medical center in Ann
      Arbor, MI, USA as part of a descriptive survey. Two hundred and thirty-five
      surveys were distributed. Mean age of the child was 8 years 6 months (SD 4y :
      9mo) and 56% of the sample was male with 35% full-time independent ambulators,
      while the rest used an assistive device or a wheelchair. Fifty-four percent were
      in special education classrooms. Families were given a survey on functional
      status of the child with CP, CAM usage of the child and the parent, factors
      influencing the decision to use CAM, demographics, and clinical information. Of
      the families, 56%, used one or more CAM techniques. Massage therapy (25%) and
      aquatherapy (25%) were the most common. Children of families that used CAM were
      significantly younger (7y : 9mo, SD 4y : 7mo) than non-users (9y : 6mo, SD 4y :
      6mo: t-test p < 0.01 two-tailed). Children with quadriplegic CP, with spasticity,
      and those who could not walk independently were more commonly exposed to CAM
      (Pearson's chi2 [P(chi)2] p = 0.01 two-tailed; for mobility, odds ratio [OR] of
      2.5 with regression). Mothers with a college degree had a greater tendency to use
      CAM for their child than those without (P(chi)2 p = 0.01 two-tailed). Fathers of
      children who used CAM were older than fathers of those who did not (37y : 9mo
      versus 33y : 2mo, p = 0.04 two-tailed). There was no significant difference
      between groups for mother's age, father's education, income, or for population of
      home town. Parents who used CAM for themselves were more likely to try CAM for
      their child (70% versus 47%, OR 2.1), and were much more likely to be pleased
      with the outcome (71% versus 42%, OR 3.5). Child's age (younger), lack of
      independent mobility, and parental use of CAM were the most significant
      predictive factors identified via logistic regression.

PMID- 12785437
TI  - Clinical and aetiological aspects of epilepsy in children with cerebral palsy.
AB  - The aims of this retrospective and population-based study were to describe the
      frequency and characteristics of epilepsy in 146 children (82 males and 64
      females) with cerebral palsy (CP) born from 1987 to 1994 in the Goteborg area of
      Sweden. The frequency of epilepsy was found to be 38% (55 children). All children
      with tetraplegic CP and about one-third of the children with other CP types
      developed epilepsy. Age at onset of epilepsy varied with type of CP: children
      with tetraplegic CP tended to have an earlier onset of epilepsy than children
      with other CP types. Partial seizures were the most common seizure type; all
      children with hemiplegic CP had partial seizures. Children with cognitive
      impairment had a higher frequency of epilepsy than those without cognitive
      impairment. CP aetiology may predict the development and outcome of epilepsy, as
      children with CP caused by CNS malformation, CNS infection, and grey matter
      damage all showed a higher frequency of epilepsy than children with CP of other
      aetiology, and also had less chance of becoming seizure-free.

PMID- 12785438
TI  - Prevalence of autistic spectrum disorder in children attending mainstream schools
      in a Welsh education authority.
AB  - All mainstream primary schools in Cardiff were invited in July 1998 to
      participate in a prevalence survey of autistic spectrum disorder. Teachers of
      each class filled in a questionnaire based on ICD-10 criteria for autistic
      disorders. The Autism Spectrum Screening Questionnaire (ASSQ) was completed on
      children identified with problems identified by the questionnaire. A total of
      11692 children born between 1 September 1986 and 31 August 1990 were screened:
      234 (2%) children were identified as requiring an ASSQ; 151 of 234 (65%) ASSQs
      were returned. Of the 151, 60 children (52 male, 8 female; 40%) scored 22 or
      more. Their notes and the involved professionals were consulted. Thirty-five
      children, unknown to specialist services or with complex features, required
      additional assessment. Seventeen children (all male) were found to be on the
      autistic spectrum. When the overall rubric was disentangled we found a diverse
      population of affected children including a handful who did not fit easily into
      ICD-10 classification. Correcting for incomplete ascertainment we found a minimum
      prevalence of 20.2 out of every 10 000 (SE = 4.5) for autistic spectrum disorder
      in this population.

PMID- 12785439
TI  - Electrical stimulation of gluteus maximus in children with cerebral palsy:
      effects on gait characteristics and muscle strength.
AB  - The purpose of this study was to determine whether electrical stimulation of the
      gluteus maximus would improve hip extensor strength, decrease excessive passive
      and dynamic internal hip rotation, and improve gross motor function in children
      with cerebral palsy (CP). Twenty-two ambulant children (15 females, 7 males, mean
      age 8 years 6 months, SD 2 years 9 months, aged 5 to 14 years) with diplegic (n =
      14), hemiplegic (n = 7), and quadriplegic (n = 1) CP participated in this study.
      All were randomly assigned to either the stimulation or control group. The
      stimulation group (n = 11) received electrical stimulation of the gluteus maximus
      of the most affected legs for 1 hour a day, 6 days a week for a period of 8
      weeks. Electrodes were applied proximally and distally over the gluteus maximus,
      with the active electrode initially positioned over the motor points. The control
      group (n = 11) did not receive any extra treatment. Measurements of hip extensor
      strength, gait analysis, passive limits of hip rotation, and section E of the
      Gross Motor Function Measure were made before and after treatment for both
      groups. Subjectively, 7 of the 11 parents thought that the treatment made a
      difference to their child. However, no statistically or clinically significant
      improvement was found in the stimulation group when compared with the control
      group.

PMID- 12785441
TI  - Individual differences in responsivity to a neurobehavioural examination predict
      crying patterns of 1-week-old infants at home.
AB  - Unexplained crying in infants aged 1 to 3 months is a common concern for Western
      parents and health services. This study examined the hypothesis that the crying
      is due to high infant responsivity, and provides evidence about the types of
      stimulation that trigger crying in infants who present with high responsivity.
      The sample included 93 eight-day-old infants from a community sample (47 females,
      46 males; mean birthweight 3457g; mean gestation 39.4 weeks; mean Apgar scores
      8.28 at 1 minute and 9.59 at 5 minutes). Infants were tested for their response
      to two standard, mildly challenging, procedures: a neurobehavioural test
      involving undressing, putting down, and handling, and the Guthrie test, involving
      a painful heel prick to obtain a blood sample. The infants' crying over 24 hours
      was recorded in parental diaries. Newborn infants who exhibited high responsivity
      during the neurobehavioural assessment cried, rather than fussed, the most at
      home. High responsivity during the neurobehavioural assessment also predicted
      those infants who cried a lot and met a definition of 'colic' at home. The
      findings support the responsivity hypothesis and show that infants with high
      responsivity are upset by undressing, putting down, and sustained handling.
      Explanations for this and implications for the management of infant crying and
      colic are discussed.

PMID- 12785440
TI  - Intrarater reliability of lower limb sagittal range-of-motion measures in
      children with spastic diplegia.
AB  - In this study, 10 sagittal lower limb range-of-motion measures were conducted in
      a blinded fashion in 25 children with spastic diplegic cerebral palsy and in 25
      age- and sex-matched controls. The participants comprised 22 males, mean age 10
      years 8 months and 28 females, with mean age 9 years 8 months; age range 6 to 17
      years. One paediatric physical therapist performed duplicate goniometric measures
      at zero time and 7 days later using the same sequence of measures, location, and
      time of day. Mean absolute differences for measures within one session ranged
      from 0.7 to 2.9 degrees in controls and from 1 to 4.2 degrees in children with
      spastic diplegia. Most intraclass correlation coefficients (ICCs) for intra
      sessional measures were more than 0.90 in both groups. Measures between sessions
      were less reliable. Mean absolute differences between sessions were up to 7.1
      degrees for children with spastic diplegia and 8.6 degrees for controls, with
      most ICCs being less than 0.80. Inter-sessional variation in measures was similar
      in both groups, suggesting that measurement variability is not influenced by the
      presence of spasticity. Averaging of two measures did not improve inter-sessional
      reliability compared with the use of a single measure. Dynamic measures (R1) were
      as reliable as passive measures (R2), but there were inter-sessional differences
      in calculations using R1 and R2 measures of up to 30 degrees.

PMID- 12785442
TI  - Peripheral neuropathies of infancy.
AB  - Over a 33-year period, 260 patients (< 17 years of age; 119 males, 141 females)
      from New South Wales, Australia who had peripheral neuropathies confirmed by
      nerve biopsy, were studied. Of these, 50 infants presented with symptoms or signs
      of neuropathy under 1 year of age: including 24 patients with demyelinating
      neuropathies and 21 axonal neuropathies; a further five patients had spinal
      muscular atrophy with associated secondary sensory axonopathy. Nineteen infants
      had hereditary motor sensory neuropathy, of whom 13 had myelin protein mutations
      confirmed by molecular genetic studies. Peripheral neuropathy is not an unusual
      diagnosis in infancy. Awareness of this association will aid early diagnosis and
      prognosis as well as facilitate interventional patient management.

PMID- 12785443
TI  - Effects of gastrostomy feeding in children with cerebral palsy: an AACPDM
      evidence report.

PMID- 12785444
TI  - 'Head growth and cranial assessment at neurological examination in infancy'.

PMID- 12785445
TI  - 'Feeding difficulties in children with visual impairment with no other
      impairments'.

PMID- 12785446
TI  - Materno-foetal exchanges and utilisation of nutrients by the foetus: comparison
      between species.
AB  - Several general features of nutrient uptake and utilisation by foetuses are
      similar among mammalian species. Nevertheless, there are also differences linked
      mainly to differences in placental permeability. Glucose and lactate are the main
      energetic substrates of the foetus. In normal conditions, the oxidation of
      carbohydrates accounts for about 75, 60 and 50% of oxygen uptake in the foetal
      pig, foal and lamb, respectively, and acetate accounts for about 10% in
      ruminants. Acidic amino acids are synthesised by the foetus, whereas neutral and
      basic amino acids are transported from the placenta. As shown by the high urea
      level in foetal blood, amino acids are partly involved in the oxidative
      metabolism of foetuses; their contribution is higher in ruminants than in humans,
      horses and pigs. Fatty acids cross the haemochorial placenta of rodents, rabbits
      and primates, and are incorporated into the foetal lipids, whereas their uptake
      by ruminant, pig and horse foetuses is very low.

PMID- 12785447
TI  - Influence of maternal environment on the number of transferable embryos obtained
      in response to superovulatory FSH treatments in ewes.
AB  - In a first experiment, embryo viability was estimated after recovery in the
      uterus or the oviduct of 70 Manchega ewes following a treatment of superovulation
      with decreasing doses of OVAGEN. Fewer viable embryos (5.6 +/- 0.9 vs. 8.3 +/-
      0.8, P < 0.05) and more degenerative embryos (31.3% vs. 6.8%, P < 0.005) were
      obtained from the uterus than from the oviduct respectively. In a second
      experiment performed on 14 ewes, embryo viability was analyzed in relation to the
      follicular population estimated by ultrasonography (follicles > or = 2 mm) at the
      first FSH administration. Progesterone (P4) and oestradiol 17beta (E2)
      concentrations were also determined from the beginning of the superovulation
      treatment to the recovery of the embryos. The number of viable embryos (4.3 +/-
      1.4) was positively correlated (r = 0.824) with of 2-4 mm diameter follicles (P <
      0.05), and with E2 concentrations at -12 h (r = 0.891, P < 0.01) , 0 h (r =
      0.943, P < 0.0001) and +24 h (r = 0.948, P < 0.05) from estrus detection.
      Prolonged high levels of E2 up to 72 h with low levels of P4 on days 3 and 4
      after estrus had a negative (P < 0.05) effect on embryo viability. These results
      indicate that ovarian response to superovulatory protocols is related to the
      individual variations in the number of follicles of 2-4 mm at the start of FSH
      treatment, and that embryo viability is conditioned by the steroid patterns
      during the time spent in the genital tract of the super-ovulated ewes.

PMID- 12785448
TI  - In situ intestinal digestibility of dry matter and crude protein of cereal grains
      and rapeseed in sheep.
AB  - The ruminal degradation and intestinal digestibility (ID) of dry matter (DM) and
      crude protein (CP) of different feed samples were measured in two trials by using
      nylon bag and rumen outflow rate techniques in three wethers cannulated in the
      rumen and in the duodenum. In trial 1, three samples of grains of wheat, barley,
      and corn treated by cooking (TW, TB, and TC, respectively) were studied together
      with a sample of untreated corn grains (CG) of different origin. In trial 2,
      these studies were carried out on a sample of rapeseed (RS) and on a mix of this
      same sample and rapeseed meal (in proportions 70:30) treated by cooking (TR). In
      both trials, the animals were fed at the same intake level (40 g DM x kg(-1)
      LW0.75) with 2:1 (DM basis) forage to concentrate diets. Rumen degradation rates
      of DM were high in the treated cereals (between 11.0 and 14.2% x h(-1)) and low
      in the CG (6.35% x h(-1)), whereas for CP these rates were low in all cereals.
      For DM, in all cereals, ID decreased linearly as the ruminal incubation time
      increased. The values of intestinal effective digestibility (IED), calculated
      from these functions and from the rumen outflow, were respectively: 86.4, 62.1,
      51.5, and 67.9%. For CP, ID was unaffected by the ruminal incubation time in corn
      samples, whereas in TW and TB a reduction of these values was only observed for
      the time of 48 h. The values of IED of CP for CG, TW, TB and TC were: 82.6,
      88.9,82.5, and 91.6%, respectively. Rumen degradation rates of the RS and TR
      samples were 8.35 and 8.23% x h(-1) for DM and 12.0 and 9.59% x h(-1) for CP. In
      RS, the ID of DM and CP showed a downward trend with an increase of the ruminal
      incubation time, as modelled according to an exponential function. This same
      trend was observed for TR after a lag period estimated at 7.53 and 6.51 h for DM
      and CP, respectively. The values of IED of RS and TR were respectively 56.5 and
      50.8% for DM and 71.9 and 80.1% for CP. These same results were also determined
      by a simplified method using a sample pooled to be representative of the rumen
      outflow of undegraded feed. The respective values for RS and TR were 54.8 and
      51.6 for DM and 65.8 and 78.9% for CP. This method seems to be a promising
      technique to estimate IED, although more studies are needed to improve its
      accuracy.

PMID- 12785449
TI  - Effect of coconut oil and defaunation treatment on methanogenesis in sheep.
AB  - The present study was conducted to evaluate in vivo the role of rumen ciliate
      protozoa with respect to the methane-suppressing effect of coconut oil. Three
      sheep were subjected to a 2 x 2 factorial design comprising two types of dietary
      lipids (50 g x kg(-1) coconut oil vs. 50 g x kg(-1) rumen-protected fat) and
      defaunation treatment (with vs. without). Due to the defaunation treatment, which
      reduced the rumen ciliate protozoa population by 94% on average, total tract
      fibre degradation was reduced but not the methane production. Feeding coconut oil
      significantly reduced daily methane release without negatively affecting the
      total tract nutrient digestion. Compared with the rumen-protected fat diet,
      coconut oil did not alter the energy retention of the animals. There was no
      interaction between coconut oil feeding and defaunation treatment in methane
      production. An interaction occurred in the concentration of methanogens in the
      rumen fluid, with the significantly highest values occurring when the animals
      received the coconut oil diet and were subjected to the defaunation treatment.
      Possible explanations for the apparent inconsistency between the amount of
      methane produced and the concentration of methane-producing microbes are
      discussed. Generally, the present data illustrate that a depression of the
      concentration of ciliate protozoa or methanogens in rumen fluid cannot be used as
      a reliable indicator for the success of a strategy to mitigate methane emission
      in vivo. The methane-suppressing effect of coconut oil seems to be mediated
      through a changed metabolic activity and/or composition of the rumen methanogenic
      population.

PMID- 12785450
TI  - The incorporation of solubilized wheat proteins in milk replacers for veal
      calves: effects on growth performance and muscle oxidative capacity.
AB  - Replacement of skim milk proteins by solubilized wheat protein (SWP) in milk
      replacers for veal calves would contribute to the reduction in feeding costs. The
      occurrence of metabolic disorders has, however, been reported. Forty-two male
      calves received one of three treatments over 140 days: a control diet, a diet
      containing SWP without or with branched-chain amino acid supplementation.
      Liveweight gain, carcass yield, color and conformation did not show any
      significant differences. No metabolic disorders were noted. Supplementation with
      branched-chain amino acids reduced the marginal Val deficiency but did not modify
      the growth performances. With the SWP containing diets, the plasma metabolite
      profile was characteristic of those observed with non-clotting diets. It was
      statistically correlated to the changes in the orientation of the Semitendinosus
      muscle energy metabolism towards a more oxidative type and to indications of a
      lower efficiency of amino acid utilisation for protein deposition. At the present
      levels of inclusion, SWP proved to be an interesting alternative to the sole use
      of whey as the protein source in milk replacers for veal calves.

PMID- 12785451
TI  - Intestinal function and body growth of broiler chickens on diets based on maize
      dried at different temperatures and supplemented with a microbial enzyme.
AB  - A study was conducted to evaluate the effects of varying drying temperature
      (Fresh, 85, 95 or 105 degrees C) on the nutritive value of maize and response of
      broiler chickens to diets based on such grain, and supplemented with a microbial
      enzyme (Avizyme 1500). The chemical composition of the grain was affected by
      drying temperature. Starch and amylopectin contents were increased while there
      was a reduction in amylose content. These changes were expected to underlie the
      response of chicks to the diets. Total feed intake over 28 days was increased (P
      < 0.05) as a result of heat-treating the maize up to 95 degrees C. The final body
      weight of chicks on the diet based on fresh maize was improved (P < 0.05) by the
      microbial enzyme supplement (MES). There was no effect of the enzyme supplement
      on body weight when assessed at earlier ages. Over the entire feeding period,
      feed conversion efficiency (FCE) declined (P < 0.001) with increasing oven
      temperature, regardless of the supplementation with the microbial enzyme. Body
      weight was influenced (P < 0.05) by the microbial enzyme only when assessed over
      the entire trial period. The weight of visceral organs, protein content and
      activities of pancreatic and jejunal digestive enzymes were unaffected by grain
      heat treatment or MES. The ileal digestibility of calcium was reduced (P < 0.001)
      on diets based on fresh maize and maize that was oven-dried at 105 degrees C.
      Heat-treatment also improved (P < 0.05) the ileal digestibility of phosphorus in
      chicks on the diets without MES. There were no effects of grain heat treatment or
      MES on the ileal digestibility of energy, protein, Ca and amino acids. The
      results indicate some variations in grain quality as a result of heat treatment
      but the differences were not significant enough to stimulate major responses to
      the MES. Further studies should examine samples from commercial drying processes
      or samples obtained from a closer simulation of commercial conditions, to arrive
      at more practical conclusions.

PMID- 12785452
TI  - Oxidative status and semen characteristics of rabbit buck as affected by dietary
      vitamin E, C and n-3 fatty acids.
AB  - The aim of this study was to investigate the effect of dietary supplementation of
      long chain fatty acids (C > or = 20 LCP) of the n-3 series, vitamin E and vitamin
      C on the antioxidant capacity of rabbit buck and on semen characteristics. Fifty
      male rabbits at 30 days were randomly assigned to five different diets: Control
      (50 mg x kg(-1) diet alpha-tocopheryl acetate), Vitamin E (200 mg x kg(-1) diet
      alpha-tocopheryl acetate), n-3 (2% ROPUFA oil + 50 mg x kg(-1) diet alpha
      tocopheryl acetate), n-3 + E (2% ROPUFA oil + 200 mg x kg(-1) diet alpha
      tocopheryl acetate) and n-3 + E C (2% ROPUFA oil + 200 mg x kg(-1) diet alpha
      tocopheryl acetate + 0.5 g x L(-1) vitamin C in the drinking water). The levels
      of vitamins E and C and reactive oxygen metabolites (ROMs) in the blood plasma
      were evaluated at different ages. The antioxidant capacity and ROMs of seminal
      plasma, the fatty acid profile of sperm phospholipids, the semen traits and the
      oxidative processes during storage (24 h at + 4 degrees C) were carried out
      weekly for 5 wk starting from the 5th month of age. Vitamin E addition showed
      enough antioxidant protection only when associated with no lipid enriched diets.
      The n-3 supplementation modified the fatty acid profile of the spermatozoa
      membrane and simultaneously enhanced oxidative processes. Only the association
      with supranutritional levels of vitamins E and C inhibited the oxidative
      processes and improved the characteristics of fresh and stored rabbit semen.

PMID- 12785454
TI  - Effect of intake on whole body plasma amino acid kinetics in sheep.
AB  - While both the quantity and quality of food ingested are potent regulators of
      whole body protein metabolism in ruminants, little data are available on
      responses across a wide range of intakes. The current study examined the
      responses in whole body protein flux (PrF) to such intake changes and compared
      these with the responses across the hind-quarters (in a companion study). Six
      growing sheep (6-8 months, 30-35 kg) received each of four intakes of dried grass
      pellets (0.5, 1.0, 1.5 and 2.5 times maintenance energy; M) for a minimum of 7
      days. At each intake, a mixture of U-13C amino-acids (AA) was infused
      intravenously for 10 h. Arterial plasma and blood were obtained over the last 4 h
      of infusion and the concentrations and the enrichments of thirteen 13C labelled
      AA were determined. The absolute values for plasma Irreversible Loss Rate (ILR)
      but also converted PrF varied between the AA. PrF values were lower for
      histidine, methionine, aspartate, glycine and proline (range 68 to 174 g x d(-1)
      at 1.5 M) than for isoleucine, leucine, valine and glutamate (range 275 to 400 g
      x d(-1) at 1.5 M). These discrepancies may be explained by (1) the differential
      AA removal by the splanchnic tissues, (2) the de novo synthesis of the non
      essential AA, (3) the transfer of AA from the erythrocytes or plasma to the
      tissues. The first two assumptions require further investigation whereas recent
      work has shown a minor role for AA transfers between erythrocytes and tissues.
      For most AA, ILR and PrF responded linearly to intake but curvilinear responses
      were observed for phenylalanine, lysine, leucine, isoleucine and tyrosine. These
      differences were not due to hind-quarter metabolism and may involve the digestive
      tract and liver.

PMID- 12785453
TI  - The effects of overfeeding on myofibre characteristics and metabolical traits of
      the breast muscle in Muscovy ducks (Cairina moschata).
AB  - The aim of this experiment was to study the consequences of precise feeding on
      the myofibre characteristics and metabolic traits of the breast muscle
      (Pectoralis major, Pm) of Muscovy ducks. Twenty-four samples of breast muscle,
      without skin or subcutaneous fat, from two groups of ducks, control and overfed
      respectively, were collected at 14 weeks of age. We assayed different chemical
      (water content, crude proteins, total lipid ashes, total and thermosoluble
      collagen), biochemical (activities of the CS, LDH and beta-HAD enzymes),
      histological (muscle fibre typing and intramuscular adipocyte measurements) and
      technological (drip and cooking losses, texture) determinations. At the force
      feeding period, the overfed ducks weighed 6366 g and the control ducks 4606 g of
      body weight. In the PM muscle, some modifications of the biochemichal parameters
      and enzyme activities were observed but neither the shear force nor the
      histological characteristics of the breast muscle were affected by the fattening
      treatment. The overfed birds had an increased total lipids content (correlated to
      an increase in the intramuscular area occupied by the adipocyte) and a different
      fatty acid profile as the result of a higher energy feed intake. The lipids of
      the Pm muscle of the overfed ducks contained more C16:0, C16:1n-7 and C18:1n-9,
      but less C18:0, C18:2n-6 and C20:4n-6 than the control birds. These results show
      that in response to high energy feeding, the muscle is able to respond quickly on
      a metabolic basis (by increasing the activities of the oxydative enzymes) without
      changing its typology or morphology. Additionally, fattening was correlated to a
      degradation in the technological qualities of the breast muscle, especially an
      increase in the cooking losses.

PMID- 12785455
TI  - State of the art of pain treatment following ambulatory surgery.
AB  - BACKGROUND AND OBJECTIVE: The growth of ambulatory surgical procedures is limited
      by severe postoperative pain. After particularly painful operative procedures,
      moderate-to-severe pain is estimated to occur in approximately 30% of patients.
      Inadequate analgesia may delay or prevent discharge, or result in readmission.
      Severe postoperative pain also causes extreme discomfort and can prevent sleep,
      thus contributing to postoperative fatigue. Moreover, postoperative pain limits
      mobility at home and delays the return to normal activities. The development of
      effective analgesia for postoperative pain is therefore a priority of modern
      medicine. RESULTS: The pain experienced during the first days spent at home is
      related to the magnitude of pain experienced at the hospital. Aggressive
      analgesic treatment at the hospital is therefore of key importance. This includes
      pre- and intraoperative administration of analgesics to reduce the pain in the
      immediate postoperative period, and the use of multimodal, balanced analgesia
      throughout recovery. Clinical studies have shown that patients who receive both
      pre- and postoperative analgesia experience greater pain relief than those who
      receive postoperative analgesia alone. Multimodal analgesia, including the use of
      anaesthetics, is increasingly important in attempts to avoid the prescription of
      single strong opioids postoperatively. The use of a non-steroidal anti
      inflammatory drug (NSAID) plus an anaesthetic perioperatively has also been shown
      to be more effective than anaesthetic alone. CONCLUSIONS: Postoperative pain is
      the most commonly reported complication of ambulatory surgery. Although the
      number of analgesic techniques seems more limited in outpatient than in inpatient
      surgery, the combination of analgesic regimens in a multimodal approach may
      improve postoperative analgesia and functional outcome after ambulatory surgery.
      The combination of acetaminophen plus tramadol is a useful formulation to
      prescribe if acetaminophen or NSAIDs alone are ineffective.

PMID- 12785456
TI  - Clinical pharmacology and rationale of analgesic combinations.
AB  - BACKGROUND AND OBJECTIVE: Oral fixed drug combination analgesics have potential
      advantages over monotherapy, but these can only be attained through careful
      design. RESULTS: The main reasons for developing combination analgesics are to
      gain efficacy and to reduce toxicity. Analgesic combinations interact
      pharmacokinetically, or pharmacodynamically, or both, in positive or negative
      terms. The t(max) value for both enantiomers of tramadol occur two hours
      following administration, and that for the active, (+)-M1 metabolite occurs after
      three hours. Thus, pairing tramadol with acetaminophen, a rapid-onset analgesic,
      represents a pharmacokinetically rational combination. Analgesic combinations
      should satisfy two important pharmacodynamic criteria: the components of the
      combination should display additive or synergistic analgesia; and this
      interaction should allow lower doses of each substance to be used in combination,
      resulting in an improved safety profile. Clinical studies of the pharmacodynamic
      between oral tramadol and acetaminophen in third molar extraction and cold
      pressor models have provided evidence that this combination provides better
      efficacy than either individual component of the combination. CONCLUSIONS: In
      summary, combination analgesics can play a valuable role in pain management.
      However, dubious combinations (directed against the same targets or with unwanted
      interactions) and 'old fashioned' fixed-dose multiple analgesic agent
      combinations should be avoided. Fixed-dose combination analgesics are of value
      only when they have been developed according to rational pharmacokinetic and
      pharmacodynamic criteria, and when claims for their benefits have been supported
      by evidence-based data and well-designed clinical studies.

PMID- 12785457
TI  - The new analgesic combination tramadol/acetaminophen.
AB  - BACKGROUND: Combinations of analgesic drugs provide the opportunity for better
      efficacy with less overall morbidity than provided by single analgesic agents.
      This article discusses the rationale, efficacy and safety for a novel analgesic
      combination: tramadol and acetaminophen (paracetamol). METHODS: Data supporting
      the rationale of combining tramadol and acetaminophen to provide pain relief will
      be reviewed in addition to clinical data demonstrating the efficacy and safety of
      this combination in acute and chronic pain states. RESULTS: Tramadol and
      acetaminophen are a rational combination product in that their mechanisms of
      action do not overlap and that in preclinical studies this combination acts
      synergistically. Also, this combination would be expected to provide more rapid
      pain relief than tramadol alone, and more persistent pain relief than
      acetaminophen alone. Moreover, each compound is broken down along separate
      metabolic pathways. Acute dental pain studies showed that pain relief and
      improvements in pain intensity associated with tramadol 75 mg plus acetaminophen
      650 mg are superior to placebo, or tramadol or acetaminophen alone. This
      combination provided a rapid onset of action, identical to that achieved with
      acetaminophen alone, but the pain relief was also sustained, as for tramadol
      alone. Tramadol/acetaminophen also had the same adverse event profile as tramadol
      monotherapy. A chronic low back/osteoarthritic pain study showed that the drug
      combination can also be used similarly to codeine/acetaminophen combinations in
      treating benign chronic pain. The safety profile of the tramadol/ acetaminophen
      combination is at least as favourable as that of codeine/acetaminophen, and is
      well tolerated with long-term use. CONCLUSIONS: Tramadol/acetaminophen
      combination is a new preparation that is effective in acute or chronic moderate
      to-moderately severe pain. It benefits from the complementary actions of the
      constituent analgesics, having the rapid onset of acetaminophen and the sustained
      effect of tramadol. The analgesic efficacy of this combination is comparable to
      that of positive controls, and its adverse event profile is in line with that of
      its single components.

PMID- 12785458
TI  - Meta-analysis of single dose oral tramadol plus acetaminophen in acute
      postoperative pain.
AB  - BACKGROUND AND OBJECTIVE: Trials in acute postoperative pain are usually small.
      Pooling homogenous data from a number of trials in a meta-analysis enables a
      truer estimate of efficacy. The aims of the present meta-analysis were to assess
      the analgesic efficacy and adverse effects of single-dose oral tramadol plus
      acetaminophen (paracetamol) in acute postoperative pain, and to demonstrate the
      efficacy of the combination formulation compared with its components. METHODS:
      Individual data from > 1400 adult dental or gynaecologic/orthopaedic patients
      with moderate-to-severe pain were taken from seven randomised, double-blind,
      placebo controlled trials of tramadol (75 mg or 112.5 mg) plus acetaminophen (650
      mg or 975 mg) with identical methods. The primary outcome measure was the number
      of patients needed to be treated (NNT) for one patient to obtain at least 50%
      pain relief. Information on adverse effects was also collected and the number
      needed to harm (NNH) was estimated. RESULTS: The tramadol/acetaminophen
      combination was more effective than either of its two components administered
      alone. For dental patients, who formed the bulk of the population, the
      combination formulation also had a significantly lower (better) NNT
      (approximately 3) than the components al one (approximately 8-12), comparable to
      ibuprofen 400 mg. The adverse effects associated with tramadol/acetaminophen were
      similar to those associated with the components alone. The commonest were
      dizziness, drowsiness, nausea, vomiting and headache. CONCLUSIONS: Meta-analysis
      confirmed the analgesic superiority of the combination treatment over its
      components, without additional toxicity. Combination analgesic formulations are
      an important and effective means of pain relief, and should prove useful in
      treating elderly and other groups of patients who often cannot tolerate non
      steroidal anti-inflammatory drugs, including the newer COX-2 inhibitors.

PMID- 12785459
TI  - Adolescent depression, cortisol and DHEA.

PMID- 12785460
TI  - Assessment and diagnosis of social phobia in the clinic and the community.

PMID- 12785461
TI  - Antidepressants for the treatment of depression in people with schizophrenia: a
      systematic review.
AB  - BACKGROUND: Depression is common in people with schizophrenia and is associated
      with substantial morbidity and an increased risk of suicide. Our aim was to
      review systematically all the randomized controlled trials that have investigated
      the clinical effectiveness of antidepressant medication in the treatment of
      depression in people who also suffer with schizophrenia. METHOD: Electronic
      searches of ClinPsych, the Cochrane Library, the Cochrane Schizophrenia Group's
      Register of Trials, EMBASE and Medline were completed. Reference lists from
      identified articles were hand searched. RESULTS: Eleven small studies were
      identified and all randomized fewer than 30 subjects to each group. We could only
      perform analyses on a subset of the trials. For five trials (aggregate N = 209)
      the proportion improved in the antidepressant group was 26% (95% CI 10% to 42%)
      higher than in the placebo group. In six studies (aggregate N = 267) the
      standardized mean difference on the Hamilton Rating Scale for Depression at the
      end of the trial was -0.27 (95 % CI -0.7 to 0.2). There was no evidence that
      antidepressant treatment given during the stable phase of illness led to a
      deterioration of psychotic symptoms in the included trials. CONCLUSIONS: The
      literature reviewed was, overall, of poor quality and only a small number of
      trials could contribute towards the meta-analysis. The results provide weak
      evidence for the effectiveness of antidepressants in those with schizophrenia and
      depression and could be explained by publication bias. We need further research
      to determine the best approach towards treating depression in people with
      schizophrenia.

PMID- 12785462
TI  - Psychoendocrine antecedents of persistent first-episode major depression in
      adolescents: a community-based longitudinal enquiry.
AB  - BACKGROUND: This longitudinal study investigated whether patterns of cortisol and
      DHEA that precede the onset of an episode of major depression influence time to
      recovery in a community ascertained sample of adolescents meeting DSM-IV criteria
      for major depression. METHOD: Sixty adolescents aged 12 to 16 at high risk for
      psychiatric disorders were followed for 24 months. At 12 months, 30 had
      experienced an episode of major depression and 30 had not. The second follow-up
      repeated the psychiatric evaluations with all participants completing the Kiddie
      SADS Schedule for Schizophrenia and Affective Disorders. Hormone characteristics
      and self-reports completed at entry (the Mood and Feelings questionnaire and the
      Ruminations scale) together with intervening undesirable life events in the 12
      months prior to onset, were used to determine the best pattern of psychosocial
      and endocrine features to predict persistent major depression. RESULTS: Compared
      to the never depressed (N = 30) and remitted adolescents (N = 19), persistently
      depressed cases (N = 11) had a raised morning cortisol/DHEA ratio at entry. Only
      persistent cases had higher levels of self-reported depressive symptoms and
      ruminations at entry compared to never depressed. There was no difference in
      exposure to undesirable life events before onset of disorder between remitted and
      persistent groups. Logistic regression techniques showed that only the
      cortisol/DHEA ratio predicted persistence. CONCLUSIONS: In community adolescents
      at high risk for psychiatric disorder persistent major depression may be
      distinguished from sporadic forms by the 08.00 h salivary cortisol/DHEA ratio
      prior to onset.

PMID- 12785463
TI  - Evaluation of the clinical global impression scale among individuals with social
      anxiety disorder.
AB  - BACKGROUND: The clinical Global Impression Scale (CGI) is commonly used as a
      primary outcome measure in studies evaluating the efficacy of treatments for
      anxiety disorders. The current study evaluated the psychometric properties and
      predictors of clinicians' ratings on an adapted version of the CGI among
      individuals with social anxiety disorders. METHOD: An independent assessor
      administered the CGI Severity of Illness and Improvement ratings to 123 patients
      at baseline and the subset of treated patients again mid- and post-treatment.
      RESULTS: Improvement ratings were strongly related to both concurrent Severity of
      Illness and changes in Severity of Illness ratings from baseline. Additionally,
      both CGI ratings were positively correlated with both self-report and clinician
      administered measures of social anxiety, depression, impairment and quality of
      life. Measures of social anxiety symptoms accounted for a large portion of the
      variance in Severity of Illness ratings, with significant additional variance
      accounted for by measures of impairment and depression. Changes in social anxiety
      symptoms from baseline accounted for significant variance in Improvement ratings,
      but no significant additional variance was accounted for by changes in impairment
      and depressive symptoms. CONCLUSIONS: Our findings support the utility of the CGI
      as an index of global severity and symptom-specific improvement among individuals
      with social anxiety disorder.

PMID- 12785464
TI  - The social phobia diagnostic questionnaire: preliminary validation of a new self
      report diagnostic measure of social phobia.
AB  - BACKGROUND: The development and validation of the Social Phobia Diagnostic
      Questionnaire (SPDQ), a new self-report diagnostic instrument for social phobia
      is described in three separate studies. STUDY 1: The participants were 125
      undergraduates seeking help for an anxiety disorder of whom 60 had social phobia.
      Receiver operating characteristics (ROC) analysis was conducted comparing SPDQ
      diagnoses and clinician-based Anxiety Disorder Interview Schedule-IV (ADIS-IV)
      diagnoses of social phobia. Diagnoses made by the SPDQ showed an 85% specificity,
      an 82% sensitivity and kappa agreement with the ADIS-IV of 0.66. STUDY 2: The
      participants were 462 undergraduates who completed the SPDQ and a battery of
      additional questionnaires. The SPDQ had good internal consistency (alpha=0.95),
      good split-half reliability (r=0.90) and strong convergent and discriminant
      validity. STUDY 3: The participants were 145 undergraduates who completed the
      SPDQ at two time points separated by 2 weeks as well as several additional
      questionnaires. Scores on the SAD, FNE and SISST of SPDQ categorized
      undergraduates were also compared to scores on these measures from 35 clinical
      community participants to determine the clinical validity of the SPDQ. The SPDQ
      had strong 2-week test-retest reliability and good convergent and discriminant
      validity. Undergraduates diagnosed with social phobia by the SPDQ were not
      significantly different on the SAD, FNE and SISST from the socially phobic
      community sample, but both groups had significantly higher scores than
      undergraduates identified by the SPDQ as not meeting criteria for social phobia,
      demonstrating clinical validity of the SPDQ. CONCLUSIONS: These three studies
      provide preliminary evidence of the strong psychometric properties of the SPDQ as
      a measure to identify socially phobic participants.

PMID- 12785465
TI  - Social phobia in the Australian National Survey of Mental Health and Well-Being
      (NSMHWB).
AB  - BACKGROUND: This article reports data on social phobia from the first large scale
      Australian epidemiological study. Prevalence rates, demographic correlates and co
      morbidity in the sample that met criteria for social phobia are reported and
      gender differences examined. METHOD: Data were obtained from a stratified sample
      of 10641 participants as part of the Australian National Survey of Mental Health
      and Well-Being (NSMHWB). A modified version of the Composite International
      Diagnostic Interview (CIDI) was used to determine the presence of social phobia,
      as well as other DSM-IV anxiety, affective and substance use disorders. The
      interview also screened for the presence of nine ICD-10 personality disorders,
      including anxious personality disorder, the equivalent of DSM-IV avoidant
      personality disorder (APD). RESULTS: The estimated 12 month prevalence of social
      phobia was 2.3%, lower than rates reported in several recent nationally
      representative epidemiological surveys and closer to those reported in the
      Epidemiological Catchment Area study (ECA) and other DSM-III studies.
      Considerable co-morbidity was identified. Data indicated that the co-morbidity
      with depression and alcohol abuse and dependence were generally subsequent to
      onset of social phobia and that the additional diagnosis of APD was associated
      with a greater burden of affective disorder. Social phobia most often preceded
      major depression, alcohol abuse and generalized anxiety disorder. CONCLUSIONS:
      Social phobia is a highly prevalent, highly co-morbid disorder in the Australian
      community. Individuals with social phobia who also screen positively for APD
      appear to be at greater risk of co-morbidity with all surveyed disorders except
      alcohol abuse or dependence.

PMID- 12785466
TI  - A brief behavioural treatment of chronic post-traumatic stress disorder in
      earthquake survivors: results from an open clinical trial.
AB  - BACKGROUND: Natural disasters such as earthquakes affect large numbers of people.
      Given the extent of the mental health problem following earthquakes, brief,
      effective and cost-effective treatment interventions are urgently needed. The
      present study examined whether cognitive-behavioural treatment could be shortened
      to a minimum number of sessions without undermining its effectiveness in post
      traumatic stress disorder (PTSD). METHOD: The study participants (N=231) were
      consecutive referrals to five project sites in the earthquake region in Turkey a
      mean of 13 months after the disaster. A modified behavioural treatment (BT) was
      used, which involved self-exposure instructions based on an enhancement of 'sense
      of control' rather than a habituation rationale and minimal cognitive
      interventions. The duration of treatment was variable, involving as many sessions
      as required for clinical improvement. Survival analysis was used to explore the
      minimum number of sessions required for clinical improvement, and multiple
      regression analysis to examine the predictors of outcome. RESULTS: The survivors
      received a mean of 4-3 sessions. Significant treatment effects and clinically
      meaningful effect sizes were noted on all measures. The treatment improved all
      PTSD and depression symptoms. The cumulative proportion of improved cases was 76%
      after one session and 88% after two sessions. No baseline variable predicted
      treatment outcome. CONCLUSIONS: The modified BT appears to be promising as an
      effective one- or two-session intervention for earthquake survivors. It may be
      particularly useful in large-scale disasters as a cost-effective treatment that
      can be relatively easily disseminated to mass populations. Further research is
      needed to clarify the possible role of a treatment focus on sense of control in
      rapid recovery from traumatic stress.

PMID- 12785467
TI  - Growth hormone responses to low-dose physostigmine administration: functional sex
      differences (sexual diergism) between major depressives and matched controls.
AB  - BACKGROUND: Considerable endocrine and non-endocrine evidence supports the
      hypothesis of increased cholinergic activity relative to noradrenergic activity
      in major depression. We previously reported functional sex differences (sexual
      diergism) in hypothalamo-pituitary-adrenal cortical (HPA) hormone responses to
      the administration of low-dose physostigmine (PHYSO), a cholinesterase inhibitor,
      in 12 female and eight male unipolar major depressives and 12 female and eight
      male individually matched control subjects. Because growth hormone (GH) secretion
      also is influenced by cholinergic mechanisms, we measured GH in the samples from
      this study. METHOD: Subjects underwent four test sessions 5-7 days apart: PHYSO
      (8 microg/kg i.v.), arginine vasopressin (AVP) (0.08 U/kg i.m.), PHYSO + AVP and
      saline control. The AVP was administered as a second stimulus to HPA axis hormone
      secretion. PHYSO and AVP produced no side-effects in about half the subjects and
      predominantly mild side-effects in the other half, with no significant patient
      control differences. Point biserial correlations between side-effects (absent or
      present) after PHYSO and the corresponding GH responses were non-significant in
      all groups. RESULTS: Afternoon baseline GH was significantly higher in the women
      than in the men, but it was not significantly different between the female or the
      male patients and their respective matched controls. AVP administration had no
      effect on GH. PHYSO administration acutely stimulated GH secretion, to a similar
      degree in the women and men. The depressed patients as a group had a
      significantly greater average post-PHYSO GH response than did their controls,
      with a trend toward a significant sex x diagnosis interaction: The female
      depressives had a significantly greater GH response than their female controls,
      whereas the male depressives had a similar GH response as their male controls.
      CONCLUSIONS: These findings suggest sexual diergism (functional sex differences)
      in baseline and cholinergically stimulated plasma GH measures between major
      depressives and matched normal controls.

PMID- 12785468
TI  - Lack of association between depressive symptoms and markers of immune and
      vascular inflammation in middle-aged men and women.
AB  - BACKGROUND: Disturbed immune activity and vascular inflammation are associated
      both with clinical depression and coronary atherogenesis, and may constitute a
      mechanism through which depression contributes to coronary heart disease. If this
      is the case, then non-clinical depressive symptoms and psychological distress
      should be associated with immune activation and vascular inflammation. We tested
      this hypothesis in a healthy middle-aged sample. METHOD: Measures of depressive
      symptoms and hopelessness were obtained from 226 volunteers (122 men, 104 women)
      aged 47-59 years, drawn from the Whitehall II epidemiological cohort. C-reactive
      protein, fibrinogen, plasma interleukin-6, tumour necrosis factor alpha,
      interleukin-1 receptor antagonist, and T- and B-lymphocyte, and natural killer
      cells numbers and percentages were assessed. RESULTS: There were no associations
      between measures of depressive symptoms or hopelessness and markers of immune
      activation or inflammatory response. CONCLUSIONS: Factors such as the measures of
      depressive symptoms, the choice of inflammatory and immune indices, and sample
      size, are unlikely to be responsible for these null effects. Associations may be
      confined to clinically depressed or older age populations, but there are problems
      of confounding by co-morbidity and health compromising behaviours in this
      literature. We conclude that disturbances of immune function and inflammatory
      processes are unlikely to be primarily responsible for the associations between
      depressive symptoms and coronary heart disease described in the literature, and
      that other pathways are involved.

PMID- 12785469
TI  - Depression with late onset is associated with right frontal lobe atrophy.
AB  - BACKGROUND: The objective of this study was to determine whether older adults
      with first-ever onset of depression after age 60 years (late onset depression,
      LOD) have smaller frontal lobes than elderly patients with early-onset depression
      (EOD) and aged controls. METHOD: Twenty-seven subjects with LOD, 24 with EOD and
      37 controls underwent volumetric MRI to determine right and left frontal lobe
      volumes and total brain volume. RESULTS: The right frontal volume of subjects
      with LOD was 8.0% and 5.6% smaller than that of patients with EOD (P < 0.01) and
      controls (NS) respectively. Volume of the left frontal lobe was not significantly
      different from EOD or controls. All analyses were adjusted for age, gender and
      total brain volume. Unlike controls and those with EOD, patients with LOD did not
      display a significant positive correlation between cognitive scores and total
      brain, left frontal or right frontal volumes. CONCLUSION: LOD is associated with
      right frontal lobe atrophy and loss of the correlation between cognitive
      performance and brain volume. This adds support to the fronto-striatal hypothesis
      of depression and suggests that structural brain changes have a particular role
      in cases of LOD.

PMID- 12785470
TI  - Slow binocular rivalry in bipolar disorder.
AB  - BACKGROUND: The rate of binocular rivalry has been reported to be slower in
      subjects with bipolar disorder than in controls when tested with drifting,
      vertical and horizontal gratings of high spatial frequency. METHOD: Here we
      assess the rate of binocular rivalry with stationary, vertical and horizontal
      gratings of low spatial frequency in 30 subjects with bipolar disorder, 30 age-
      and sex-matched controls, 18 subjects with schizophrenia and 18 subjects with
      major depression. Along with rivalry rate, the predominance of each of the
      rivaling images was assessed, as was the distribution of normalized rivalry
      intervals. RESULTS: The bipolar group demonstrated significantly slower rivalry
      than the control, schizophrenia and major depression groups. The schizophrenia
      and major depression groups did not differ significantly from the control group.
      Predominance values did not differ according to diagnosis and the distribution of
      normalized rivalry intervals was well described by a gamma function in all
      groups. CONCLUSIONS: The results provide further evidence that binocular rivalry
      is slow in bipolar disorder and demonstrate that rivalry predominance and the
      distribution of normalized rivalry intervals are not abnormal in bipolar
      disorder. It is also shown by comparison with previous work, that high strength
      stimuli more effectively distinguish bipolar from control subjects than low
      strength stimuli. The data on schizophrenia and major depression suggest the need
      for large-scale specificity trials. Further study is also required to assess
      genetic and pathophysiological factors as well as the potential effects of state,
      medication, and clinical and biological subtypes.

PMID- 12785472
TI  - Family study of co-morbidity between major depressive disorder and anxiety
      disorders.
AB  - BACKGROUND: Numerous studies have documented high rates of co-morbidity between
      major depressive disorder (MDD) and the anxiety disorders (ANX). However, the
      reason for this is unclear. Family studies provide one potentially useful
      approach for addressing this issue. METHOD: We explored six explanations of the
      co-morbidity between MDD and ANX using a family study of a large community sample
      of young adults and their first-degree relatives. Participants included 112
      probands with a lifetime history of both MDD and one or more ANX, 290 probands
      with a history of MDD but no ANX, 43 probands with a history of one or more ANX
      but no MDD. 352 probands with no lifetime history of either MDD or ANX, and the
      probands' 2608 first-degree relatives. Probands were assessed using semi
      structured diagnostic interviews on two occasions in adolescence and a third time
      at age 24. Diagnostic data on relatives were collected using both direct and
      family history interviews. RESULTS: Compared with controls, MDD aggregated in the
      families of probands with MDD, whether or not they had co-morbid ANX; ANX
      aggregated in the families of probands with ANX, regardless of whether they had
      co-morbid MDD; and co-morbid MDD/ANX aggregated only in the families of probands
      with both MDD and ANX. The relatives of probands with ANX alone had a
      significantly higher rate of ANX than the relatives of probands with MDD alone,
      although none of the other comparisons between the depressed and anxious groups
      were significant. CONCLUSIONS: This pattern of findings is largely, although not
      completely, consistent with the view that MDD and ANX are transmitted
      independently within families, and suggests that the comorbidity between MDD and
      ANX is caused by non-familial aetiological factors.

PMID- 12785471
TI  - Patient's therapeutic skill acquisition and response to psychotherapy, alone or
      in combination with medication.
AB  - BACKGROUND: We tested the hypotheses that the addition of medication to
      psychotherapy enhances participation in the latter by: (1) speeding the
      acquisition of the psychotherapy's targeted skill; and (2) facilitating higher
      skill level acquisition. METHOD: Participants were 431 chronically depressed
      patients who received Cognitive Behavioral Analysis System of Psychotherapy
      (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a
      randomized chronic depression study (Keller et al. 2000). CBASP, developed
      specifically to treat chronic depression, uses a specific procedure, 'situational
      analysis' to help patients engage in more effective goal-oriented interpersonal
      behaviours. At the end of each session, therapists rated patients on their
      performance of situational analysis. Outcome on depressive symptoms was assessed
      with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although
      reductions in depression were significantly greater in combined treatment
      compared to CBASP alone, there were no between-group differences in either the
      rate of skill acquisition or overall skill level at the end of treatment.
      Proficiency in the use of the main skill taught in psychotherapy at treatment
      midpoint predicted outcome independently of medication status and of baseline
      depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected
      by proficiency in the compensatory skill taught in psychotherapy, is not enhanced
      by the addition of medication and does not mediate the between-group difference
      in depression outcome.

PMID- 12785473
TI  - Lone mothers, social exclusion and depression.
AB  - BACKGROUND: In this paper, data from the British National Survey of Psychiatric
      Morbidity are used to assess depressive disorders and markers of social
      disadvantage in women bringing up children on their own. METHOD: The household
      component of the British National Surveys of Psychiatric Morbidity was based on a
      stratified random sample of > 10000 subjects. This paper reports on 5281 women
      interviewed in person. Psychiatric symptoms and ICD-10 diagnoses were established
      by lay interviewers using the CIS-R. Results are presented in terms of depressive
      episode and mixed anxiety/depressive disorder. Housing tenure and access to a car
      were used as proxy measures of material status. The life event rate in the 6
      months before interview was used to indicate overall exposure to stress, and
      subjects were asked in detail about perceived social support. Information was
      collected about various other sociodemographic attributes. Lone mothers were
      compared with supported mothers and with women not involved in care of children
      under 16. RESULTS: Lone mothers had prevalence rates of depressive episode of 7%,
      about three times higher than any other group. The milder condition, mixed
      anxiety/depression, was also increased in frequency. These increased rates of
      depressive conditions were no longer apparent after controlling for measures of
      social disadvantage, stress and isolation. CONCLUSIONS: Lone mothers are
      increasing in numbers as marital stability declines. Their high rates of material
      disadvantage and of depressive disorder may have considerable implications for
      psychiatric and social policy.

PMID- 12785474
TI  - Association between psychotic disorder and urban place of birth is not mediated
      by obstetric complications or childhood socio-economic position: a cohort study.
AB  - BACKGROUND: Although urban place of birth has been identified as a risk factor
      for schizophrenia, the extent to which this association is mediated by socially
      patterned risk factors such as obstetric complications and childhood socio
      economic position is unclear. The diagnostic specificity of the association
      within the clinical psychotic syndromes is also unclear. METHOD: A population
      cohort of 696025 males and females, born in Sweden between 1973 and 1980 and with
      linked birth and socio-economic data was followed up from age 16 for up to 9.8
      years. Hospitalized cases of schizophrenia and other non-affective psychosis were
      identified from the Swedish Inpatient Discharge Register. We examined
      associations of these disorders with a three-level measure of urbanicity of
      birthplace before and after controlling for measures of foetal nutrition,
      obstetric complications and level of maternal education. RESULTS: Urban compared
      to rural birthplace was associated both with increased risk of adult onset
      schizophrenia (hazard ratio 1.34, CI 0.91-1.96) and other non-affective psychoses
      (hazard ratio 1.63, CI 1.18-2.26). None of these associations was greatly
      affected by adjustment for obstetric complications or maternal educational level.
      In the group of other non-affective psychoses urban-rural differences in disease
      risk were strongest among those born in the winter months. CONCLUSION:
      Urbanization of birthplace is associated with increased risk of non-affective
      psychosis but this is not confined to narrowly defined cases. The magnitude of
      the association in Sweden is lower than that reported in other studies. Causal
      factors underlying this association appear to operate independently of risks
      associated with obstetric complications and parental educational status.

PMID- 12785475
TI  - The relationship between agoraphobia symptoms and panic disorder in a non
      clinical sample of adolescents.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical correlates of
      agoraphobic fear and avoidance and panic disorder in a non-clinical sample of
      adolescents. METHOD: In a sample of 2365 high school students, combined data from
      a questionnaire and a structured clinical interview were used to classify
      subjects with agoraphobic fear and avoidance. Panic symptoms, major depression,
      childhood separation anxiety disorder, anxiety sensitivity and negative
      affectivity were also assessed. RESULTS: Fifteen subjects met study criteria for
      agoraphobic fear and avoidance in the past year. Only three (20%) of those with
      agoraphobia symptoms reported histories of panic attacks and there was no overlap
      between those with agoraphobic fear and avoidance and the 12 subjects who met DSM
      III-R criteria for panic disorder. However, subjects with agoraphobia symptoms
      and those with panic disorder reported similar levels of anxiety sensitivity and
      negative affectivity. Childhood separation anxiety disorder was more common among
      those with agoraphobic fear and avoidance compared to those without. CONCLUSION:
      Agoraphobic avoidance is rare in non-clinical samples of adolescents and usually
      not associated with panic attacks. However, adolescents with agoraphobia symptoms
      and those with panic disorder have similar clinical correlates consistent with a
      panic/agoraphobia spectrum model.

PMID- 12785477
TI  - A meta-analysis of family intervention studies in schizophrenia.

PMID- 12785476
TI  - The perception of emotional chimeric faces in patients with depression, mania and
      unilateral brain damage.
AB  - BACKGROUND: Judgements made on chimeric faces elicit reliably a perceptual bias
      to the left hemispace, presumed to be due to right hemisphere dominance for
      emotional processes. Major depressive illness has been shown to attenuate this
      bias. The aim of this work was to examine lateral perceptual bias in bipolar I
      and II patients in a hypomanic state and unipolar depressed patients and those
      with unilateral hemisphere damage following stroke. METHOD: Sixty patients with
      DSM-IV affective disorder (30 bipolar I or II, currently hypomanic, 30 unipolar
      depressives), 30 right brain-damaged patients, 30 left brain-damaged patients and
      30 healthy controls were given the Happy-Sad Chimeric Faces Test. RESULTS: Right
      hemisphere damaged and unipolar depressed patients both showed a significantly
      reduced left hemispatial bias (LHB) compared to controls, bipolars and left brain
      damaged patients. No significant difference in mean LHB between controls and both
      hypomanics and left brain-damaged patients was found. There was no significant
      association between LHB and clinical variables. CONCLUSIONS: The results suggest
      a physiological distinction between bipolar and unipolar depression. The
      significantly diminished left hemifacial bias in depressed patients suggests
      right hemisphere dysfunction.

PMID- 12785478
TI  - Meta-analyses of randomized controlled trials of social skills training and
      cognitive remediation.

PMID- 12785479
TI  - Another Babel.

PMID- 12785480
TI  - Comparison at a distance.
AB  - The visual system is known to contain hard-wired mechanisms that compare the
      values of a given stimulus attribute at adjacent positions in the visual field;
      but how are comparisons performed when the stimuli are not adjacent? We ask
      empirically how well a human observer can compare two stimuli that are separated
      in the visual field. For the stimulus attributes of spatial frequency, contrast,
      and orientation, we have measured discrimination thresholds as a function of the
      spatial separation of the discriminanda. The three attributes were studied in
      separate experiments, but in all cases the target stimuli were briefly presented
      Gabor patches. The Gabor patches lay on an imaginary circle, which was centred on
      the fixation point and had a radius of 5 deg of visual angle. Our psychophysical
      procedures were designed to ensure that the subject actively compared the two
      stimuli on each presentation, rather than referring just one stimulus to a stored
      template or criterion. For the cases of spatial frequency and contrast, there was
      no systematic effect of spatial separation up to 10 deg. We conclude that the
      subject's judgment does not depend on discontinuity detectors in the early visual
      system but on more central codes that represent the two stimuli individually. In
      the case of orientation discrimination, two naive subjects performed as in the
      cases of spatial frequency and contrast; but two highly trained subjects showed a
      systematic increase of threshold with spatial separation, suggesting that they
      were exploiting a distal mechanism designed to detect the parallelism or non
      parallelism of contours.

PMID- 12785481
TI  - Measuring the depth induced by an opposite-luminance (but not anticorrelated)
      stereogram.
AB  - The same-sign hypothesis suggests that only those edges in the two retinal images
      whose luminance gradients have the same sign, known as same-sign edges, can be
      stereoscopically fused to generate a perception of depth. If true, one would
      expect that the magnitude of the depth induced by an opposite-luminance
      stereogram (eg one where the figure in one stereo half-image is black and the
      figure in the other is white) should be determined by the disparity of the same
      sign edges. Despite the considerable work on the same-sign hypothesis this
      prediction has yet to be verified. Here we confirm this prediction for a
      particular opposite-luminance stereogram and discuss possible reasons why it is
      not true for opposite-luminance stereograms that are presented briefly or where
      each stereo half-image contains many elements.

PMID- 12785482
TI  - Directional harmonic theory: a computational Gestalt model to account for
      illusory contour and vertex formation.
AB  - Visual illusions and perceptual grouping phenomena offer an invaluable tool for
      probing the computational mechanism of low-level visual processing. Some
      illusions, like the Kanizsa figure, reveal illusory contours that form edges
      collinear with the inducing stimulus. This kind of illusory contour has been
      modeled by neural network models by way of cells equipped with elongated spatial
      receptive fields designed to detect and complete the collinear alignment. There
      are, however, other illusory groupings which are not so easy to account for in
      neural network terms. The Ehrenstein illusion exhibits an illusory contour that
      forms a contour orthogonal to the stimulus instead of collinear with it. Other
      perceptual grouping effects reveal illusory contours that exhibit a sharp corner
      or vertex, and still others take the form of vertices defined by the intersection
      of three, four, or more illusory contours that meet at a point. A direct
      extension of the collinear completion models to account for these phenomena tends
      towards a combinatorial explosion, because it would suggest cells with
      specialized receptive fields configured to perform each of those completion
      types, each of which would have to be replicated at every location and every
      orientation across the visual field. These phenomena therefore challenge the
      adequacy of the neural network approach to account for these diverse perceptual
      phenomena. I have proposed elsewhere an alternative paradigm of neurocomputation
      in the harmonic resonance theory (Lehar 1999, see website), whereby pattern
      recognition and completion are performed by spatial standing waves across the
      neural substrate. The standing waves perform a computational function analogous
      to that of the spatial receptive fields of the neural network approach, except
      that, unlike that paradigm, a single resonance mechanism performs a function
      equivalent to a whole array of spatial receptive fields of different spatial
      configurations and of different orientations, and thereby avoids the
      combinatorial explosion inherent in the older paradigm. The present paper
      presents the directional harmonic model, a more specific development of the
      harmonic resonance theory, designed to account for specific perceptual grouping
      phenomena. Computer simulations of the directional harmonic model show that it
      can account for collinear contours as observed in the Kanizsa figure, orthogonal
      contours as seen in the Ehrenstein illusion, and a number of illusory vertex
      percepts composed of two, three, or more illusory contours that meet in a variety
      of configurations.

PMID- 12785483
TI  - Search of jumping items: visual marking and discrete motion.
AB  - Watson and Humphreys (1997 Psychological Review 104 90-122) showed that when
      searching for a target, observers can ignore a previewed set of distractors
      (other items), effectively decreasing the number of relevant items in a difficult
      search display and thus speeding performance ('visual marking'). Other
      researchers have more recently investigated visual marking for continuously
      moving items, finding that shared features, and preserved inter-item spatial
      relationships, are helpful. Here, we tested whether visual marking occurs for a
      set of initial items that moves in one discrete jump (preserving shared features
      and inter-item spatial relationships). Marking did not occur in these displays,
      and we interpret this result in the context of previous research on visual
      marking.

PMID- 12785484
TI  - Saccadic suppression of displacement: effects of illumination and background
      manipulation.
AB  - In contrast to other functions which are suppressed during saccades, saccadic
      suppression of displacement (SSD--a decrease in sensitivity to visual
      displacements during saccades) has often been considered to be due to efferent
      processes rather than to visual masking. The aim of this study was to explicitly
      assess the importance of visual conditions in SSD. In two experiments, a small
      computer-generated target made random horizontal jumps. An infrared eye tracker
      was used to detect the saccade toward the new position, triggering a smaller
      centripetal displacement of the target. Subjects reported awareness of these
      intrasaccadic displacements by pressing a key. In the first experiment, the task
      was performed in both a well-lit environment and in darkness. In the second
      experiment these conditions were replicated and additional factors such as the
      contrast of the background and the effect of moving the target spot alone or the
      target plus the entire background were investigated. Unlike other forms of
      saccadic suppression, SSD was stronger in the dark, although subjects also had a
      greater bias to report detections in that condition. Other background
      manipulations had no effect. The effect of ambient lighting on SSD is small and
      subtle. Effects of other background manipulations may be overridden by the
      focusing of attention on a small moving target.

PMID- 12785485
TI  - Attentional modulation of self-motion perception.
AB  - Attentional effects on self-motion perception (vection) were examined by using a
      large display in which vertical stripes containing upward or downward moving dots
      were interleaved to balance the total motion energy for the two directions. The
      dots moving in the same direction had the same colour, and subjects were asked to
      attend to one of the two colours. Vection was perceived in the direction opposite
      to that of non-attended motion. This indicates that non-attended visual motion
      dominates vection. The attentional effect was then compared with effects of
      relative depth. Clear attentional effects were again found when there was no
      relative depth between dots moving in opposite directions, but the effect of
      depth was much stronger for stimuli with a relative depth. Vection was mainly
      determined by motion in the far depth plane, although some attentional effects
      were evident even in this case. These results indicate that attentional
      modulation for vection exists, but that it is overridden when there is a relative
      depth between the two motion components.

PMID- 12785486
TI  - Children's search for targets located within and beyond the field of view:
      effects of deafness and age.
AB  - The localisation time of visual targets within and beyond the field of view and
      the relative timing of the onsets of eye and head movements were examined in deaf
      and hearing children of two age groups: 5-7 years and 10-12 years. Compared to
      their hearing peers, the deaf children showed more often a mode of eye-head
      coordination in which the head leads the eye. The discrepancy between the onsets
      of eye and head movements were greater for the younger than for the older groups.
      Furthermore, the deaf children took more time than the hearing children to
      localise the targets; especially the young deaf differed from their hearing
      contemporaries. These findings support the view that during development the
      differences in visual search between deaf and hearing children decrease. The
      results are discussed in the context of a distinction between representational
      and sensorimotor control of eye-head responses.

PMID- 12785487
TI  - Superior haptic perceptual selectivity in late-blind and very-low-vision
      subjects.
AB  - Blindfolded sighted, congenitally blind, late-blind, and very-low-vision subjects
      were tested on a tangible version of the embedded-figures test. The results of
      ANOVAs on accuracy measures yielded superior performance by the very-low-vision
      and late-blind subjects compared with the blindfolded sighted and congenitally
      blind participants. Accuracy of the congenitally blind subjects was similar to
      that of the blindfolded sighted participants. However, all groups of blind
      subjects were significantly faster than the blindfolded sighted subjects. It is
      suggested that experience with pictures combined with haptic skill aid perceptual
      selectivity in touch.

PMID- 12785488
TI  - Oversimplifying partial dentures?

PMID- 12785489
TI  - Dental Head Start in jeopardy.

PMID- 12785490
TI  - Sjogren's syndrome: a clarification.

PMID- 12785491
TI  - Infection control: its evolution to the current standard precautions.
AB  - BACKGROUND: The use of appropriate infection control precautions to protect
      against transmission of bloodborne and other occupational microbial pathogens has
      become a routine component of health care provision. Evolution and revision of
      recommendations continues to be based on updated scientific information, as well
      as documented and inferred clinical applications of new knowledge. In addition,
      surveillance of occupational risks in medical treatment settings often has served
      as a basis for subsequent disease prevention recommendations for dental care.
      TYPES OF STUDIES REVIEWED: Guidelines designed to protect dental professionals
      and their patients have focused on bloodborne pathogens since the first published
      American Dental Association recommendations in the 1970s. Subsequent statements
      developed by the Centers for Disease Control and Prevention, the ADA and other
      organizations during the past 30 years also have addressed prevention of other
      infections, transmitted by either direct or indirect contact with a variety of
      potentially infectious body fluids. RESULTS: Review of the major features of
      these recommendations provides an appropriate framework to consider current
      guideline revisions. The success of long-standing universal precautions, or UP,
      against bloodborne infection has been augmented with the incorporation of body
      substance isolation, or BSI, practices into the infection control protocol
      designated "standard precautions." Combination of the major tenets of UP with the
      BSI systems routinely employed in acute care facilities affords all health care
      professionals the means of preventing a spectrum of bloodborne, respiratory,
      contact and other potential exposures during provision of patient care. CLINICAL
      IMPLICATIONS: As infection control recommendations for dentistry are updated this
      year, they undoubtedly will include guidelines expanding previous UP to provide
      expanded protection for dental professionals in the multiple types of nonacute
      treatment settings in which routine treatment is provided.

PMID- 12785492
TI  - Assessing periodontal disease risk: a comparison of clinicians' assessment versus
      a computerized tool.
AB  - BACKGROUND: The authors conducted a study to compare risk scores assigned by
      subjective expert clinician opinion with quantitative scores generated for the
      same subjects using the Periodontal Risk Calculator, or PRC. METHODS: The authors
      assembled a group of 107 subjects and performed standard periodontal
      examinations. The authors entered the resulting information into the PRC and
      calculated risk scores for two and four years, assuming no treatment would be
      performed. Using the same subject records, three groups of expert clinicians
      assigned risk scores for years 2 and 4. The authors analyzed the data to reveal
      the extent of interevaluator variation and the level of agreement between expert
      clinician scores and PRC scores. RESULTS: The extent of variation among scores
      assigned by individual expert clinicians was greater than the authors had
      expected. Expert clinicians consistently assigned more subjects to PRC risk group
      2 and fewer to risk group 5 than did the PRC. The authors observed very high
      heterogeneity in the risk scores expert clinicians assigned to patients in each
      of the PRC-assigned groups. Thus, expert clinicians varied greatly in evaluating
      risk and, relative to the PRC, they appeared to underestimate periodontitis risk,
      especially for high-risk patients. CONCLUSIONS AND PRACTICE IMPLICATIONS: The
      authors' observations suggest that use of risk scores generated for individual
      patients by subjective expert clinician opinion about risk in periodontal
      clinical decision making could result in the misapplication of treatment for some
      patients and support the use of an objective tool such as the PRC. Use of the PRC
      over time may be expected to result in more uniform and accurate periodontal
      clinical decision making, improved oral health, reduction in the need for complex
      therapy and reduction in health care costs.

PMID- 12785493
TI  - Clinical versus statistical significance as they relate to the efficacy of
      periodontal therapy.
AB  - BACKGROUND: The author discusses the shortcomings of using statistical
      significance testing as a method to infer that results of periodontal clinical
      trials are clinically meaningful. To compensate for these deficiencies, he also
      identifies criteria and periodontal parameters that can be used to reflect
      clinically significant outcomes. TYPES OF STUDIES REVIEWED: The author searched
      the medical and dental literature to identify commentaries that addressed the
      problems associated with interpreting statistical significance testing, or
      hypothesis testing, and defining clinical significance. RESULTS: The limitations
      of statistical significance testing related to identifying clinically significant
      changes include failure to indicate if the detected differences between variables
      in test and control groups are large or important. After reviewing various
      definitions of the term "clinical significance," the author reviews and proposes
      a comprehensive working definition of it. Regarding the efficacy of periodontal
      therapy, he delineates the advantages and limitations of specific criteria (such
      as absolute values, cut points) that can be used to define clinical significance.
      CLINICAL IMPLICATIONS: The author suggests that clinically significant results
      should be defined before initiating a study and statistical significance testing
      should be used to validate that findings did not occur by chance. This would help
      place the importance of clinical data into perspective, and it would enhance
      clinicians' ability to select the most appropriate therapies for particular sites
      in periodontal patients.

PMID- 12785494
TI  - The complexities involved with managing the care of an elderly patient.
AB  - BACKGROUND: Treatment planning for and managing the care of elderly patients can
      be complicated for a number of reasons. To understand the patient's needs, one
      must understand the environment in which the patient functions. CASE DESCRIPTION:
      The authors present a case that illustrates some of the social, economic,
      financial and transportation issues that are involved in treating elderly
      patients, as well as how the dynamics of the interpersonal relationships
      influence the final treatment. CLINICAL IMPLICATIONS: A dental treatment plan can
      be difficult to outline to a patient because modifying factors may make care
      complex and difficult to manage. This requires good communication among the
      dentist, patient and family.

PMID- 12785495
TI  - Identifying rosacea: what all dentists should know.
AB  - BACKGROUND: Dentists frequently encounter adult patients who have facial rosacea.
      This common dermatologic condition can undermine a patient's appearance. Although
      rosacea can be progressive, the condition responds well to treatment, especially
      when started early. RESULTS: This article will help dentists recognize rosacea
      and differentiate it from other dermatologic disorders. Clinicians then will be
      able to refer patients suspected of having rosacea to the appropriate medical
      specialist for confirmation of the diagnosis and treatment. CONCLUSION: Dentists
      can provide a service to patients to improve their overall health and appearance
      by early recognition of this condition. CLINICAL IMPLICATIONS: Recognizing
      rosacea in dental patients and properly referring them for diagnosis and
      treatment constitutes a medical service that is relatively easy for dentists to
      perform. This service, in addition to others, such as measuring blood pressure,
      will make the dental examination more comprehensive.

PMID- 12785496
TI  - The efficacy of luting all-ceramic crowns with resin-modified glass ionomer
      cement.
AB  - BACKGROUND: The authors conducted studies to determine if hygroscopic expansion
      of resin-modified glass ionomer, or RMGI, cement would cause fracture of the
      sintered aluminum oxide copings of all-ceramic crowns. MATERIALS AND METHODS: The
      authors scanned standardized dies using computer-aided design/computer-aided
      manufacture technology. Aluminum oxide copings were fabricated, inspected and
      luted onto titanium dies. The copings were seated with 11 pounds of force for 10
      minutes. The copings were placed in a container with 100 percent humidity and
      stored at room temperature. At appropriate intervals, the authors inspected the
      copings with surgical loupes and under microscopic magnification. The authors
      also inspected the copings before conducting load testing. RESULTS: After six and
      12 weeks, the authors found no signs of fracture in any of the 30 copings
      cemented with one of two RMGI cements. Seventeen additional samples were
      inspected four years after cementation, and no fractures were evident. In a
      follow-up study, the authors cemented 18 copings with RMGI cement one week before
      testing, 10 weeks before testing or 60 weeks before testing. Using a universal
      testing machine, they loaded the samples to fracture at 0.5 millimeter/minute.
      Statistical analysis indicated a significant difference in the mean load-to
      fracture values between the samples tested one week after cementation and those
      tested 60 weeks after cementation. CONCLUSIONS: The results showed no fracture of
      the all-ceramic copings as a result of expansion of the cement alone. The mean
      load-to-fracture values were significantly greater for the group tested 60 weeks
      after cementation. CLINICAL IMPLICATIONS: The all-ceramic crowns examined in this
      study demonstrated excellent esthetics, incorporated a strong coping system and
      allowed ease of cement choice.

PMID- 12785497
TI  - How can oral health care providers determine if patients have dry mouth?
AB  - BACKGROUND: Dentists recognize the importance of saliva in maintaining oral
      health and often are familiar with the clinical effects an insufficient salivary
      flow can have on oral tissues. A variety of medical conditions and medications
      can alter salivary secretion and composition. Typically, diagnosis of
      hyposalivation is made only after damage has occurred to the oral tissues.
      OVERVIEW: The author describes a series of clinical steps that, if followed
      properly, may help in the early detection of salivary gland hypofunction and
      prevention of its severe complications. This four-step approach includes
      identifying a patient's chief complaint and the symptoms and duration of illness
      that brought the patient to the dentist, as well as any approaches the patient
      took to relieve symptoms; obtaining a medical history that includes a review of
      the body systems; performing a clinical evaluation that notes the patient's
      overall condition in addition to the health and functioning of the salivary
      glands and oral soft and hard tissues; and, when needed, conducting further
      diagnostic evaluations. CONCLUSIONS AND CLINICAL IMPLICATIONS: Oral health care
      providers will continue to face the challenges of treating new and recurrent
      carious lesions if the profession's approach to salivary hypofunction remains
      reactive rather than proactive. The recommendations in this article may enhance
      clinicians' awareness of the objective methods used to identify patients with
      salivary gland hypofunction or those at risk of developing it. It is hoped that
      early identification of asymptomatic patients at risk of developing
      hyposalivation, as well as symptomatic patients will lower the incidence and
      prevalence of dental caries and fungal infection in this population and
      ultimately enhance their quality of life.

PMID- 12785499
TI  - Injectable local anesthetics.

PMID- 12785498
TI  - Recent trends in dental visits and private dental insurance, 1989 and 1999.
AB  - BACKGROUND: This article describes recent trends in dental visits and private
      dental insurance in the United States. METHODS: This study is based on the
      analyses of data regarding dental visits and private dental insurance among the
      population 2 years of age or older from the 1989 and 1999 National Health
      Interview Surveys. RESULTS: Overall, the percentage of the population with a
      dental visit rose from 57.2 percent in 1989 to 64.1 percent in 1999, while the
      percentage with private dental insurance fell from 40.5 percent to 35.2 percent.
      CONCLUSIONS: Although a higher percentage of people with private dental insurance
      reported having a dental visit than did those without private dental insurance in
      both years, the increase from 1989 to 1999 in the percentage of those with a
      visit was larger among the uninsured. PRACTICE IMPLICATIONS: If this trend
      persists, a smaller portion of practicing dentist's clientele will be insured.
      This may affect demand for services, as well as front office operations.

PMID- 12785500
TI  - The fastest and best provisional restorations.
AB  - Many options are available for PRs for teeth prepared for crowns, veneers,
      inlays, onlays or fixed prosthetic abutments. Dentists and dental assistants
      (where allowed by law) should know the physical properties of the various types
      of materials and should be able to select and place the appropriate type of PR
      based on the needs of specific clinical situations.

PMID- 12785501
TI  - HIPAA security regulations: protecting patients' electronic health information.

PMID- 12785502
TI  - The business of dentistry.
AB  - Dentistry is a rapidly evolving health care occupation that can offer an
      outstanding quality of life, allowing each doctor to define how he or she would
      like to practice. Dentistry has a high-income potential compared with many other
      occupations, and this also contributes to the quality of life of dental
      professionals. But the profession can be overwhelming due to the variety of
      procedures performed, the large number of systems in place and the multiple
      management issues to deal with. While there is no one-size-fits-all system that
      will work for all practices, KPIs can help each professional evaluate how he or
      she would like the practice to operate and grow. Using KPIs to help identify the
      strengths and weaknesses of your practice, you can set and establish the systems
      that will assure achievement of those goals.

PMID- 12785503
TI  - For the dental patient. Kicking the habit. Keeping your smile healthy.

PMID- 12785504
TI  - Why and how should we assess occupational health impacts in integrated product
      policy?
AB  - Integrated product policy (IPP) and life cycle assessment (LCA), one of the
      analytic tools used in IPP, focus traditionally on environmental impacts.
      However, in an attempt to consider other sustainability criteria and to avoid a
      shift from environmental health impacts to occupational health impacts one may
      want to include occupational health in IPP. Should and can occupational health
      impacts be included in LCA and IPP? Using published and unpublished occupational
      health data for injuries and illnesses and an economic input-output model of the
      United States, we provide attributional occupational health impacts measured in
      disability adjusted life years per dollars output for 491 industry sectors
      including supply chain impacts. Estimates for the "true" number of United States
      occupational health impacts suggest that this initial analysis underestimates the
      total impact 3-7-fold. A comparison suggests that United States occupational
      health impacts are about 10 times smaller than environmental health impacts and
      are, relatively speaking, important only for sectors with hazardous working
      environments but low environmental impacts. A consequential rather than
      attributional view suggests that a method to assess true consequences on long
      term health impacts by product policies needs to be able to predict effects from
      present-day work place exposure and to account for likely changes in the labor
      market, including changes in unemployment rates and other substitution
      mechanisms.

PMID- 12785505
TI  - Chemical response of lakes in the Adirondack Region of New York to declines in
      acidic deposition.
AB  - Long-term changes in the chemistry of wet deposition and lake water were
      investigated in the Adirondack Region of New York. Marked decreases in
      concentrations of SO4(2-) and H+ in wet deposition have occurred at two sites
      since the late 1970s. These decreases are consistent with long-term declines in
      emissions of sulfur dioxide (SO2) in the eastern United States. Changes in wet
      NO3- deposition and nitrogen oxides (NOx) emissions have been minor over the same
      interval. Virtually all Adirondack Lakes have shown marked decreases in
      concentrations of SO4(2-), which coincide with decreases in atmospheric S
      deposition. Concentrations of NO3- have also decreased in several Adirondack
      lakes. As atmospheric N deposition has not changed over this period, the
      mechanism contributing to this apparent increase in lake/watershed N retention is
      not evident. Decreases in concentrations of SO4(2-) + NO3- have resulted in
      increases in acid-neutralizing capacity (ANC) and pH and resulted in a shift in
      the speciation of monomeric Al from toxic inorganic species toward less toxic
      organic forms in some lakes. Nevertheless, many lakes continue to exhibit pH
      values and concentrations of inorganic monomeric Al that are critical to aquatic
      biota. Extrapolation of rates of ANC increase suggests that the time frame of
      chemical recovery of Adirondack Lakes will be several decades if current
      decreases in acidic deposition are maintained.

PMID- 12785506
TI  - Assessing TMDL effectiveness using flow-adjusted concentrations: a case study of
      the Neuse River, North Carolina.
AB  - Integrated control of both point and nonpoint source water pollution using Total
      Maximum Daily Load (TMDL) assignments will be a major regulatory focus over the
      next decade. We propose the use of "flow-adjusted" pollutant concentrations to
      evaluate the effectiveness of management actions taken to meet approved TMDLs.
      Pollutant concentrations are usually highly correlated with streamflow, and flow
      is strongly weather-dependent. Thus, pollutant loads, which are calculated as
      pollutant concentration multiplied by streamflow, have a large weather-dependent
      variance component. This natural variation can be removed by calculating flow
      adjusted concentrations. While such values are not a direct measure of pollutant
      load, they make it easier to discern changes in streamwater quality.
      Additionally, they are likely to be a better predictor of pollutant
      concentrations in the receiving waterbody. We demonstrate the use of this
      technique using long-term nutrient data from the Neuse River in North Carolina.
      The Neuse River Estuary has suffered many eutrophication symptoms, and a program
      to reduce nutrient loading has been in place for several years. We show that, in
      addition to revealing recent reductions in nutrient inputs, annual flow-adjusted
      riverine nutrient concentrations show a more pronounced relationship with
      estuarine nutrient concentrations than do annual nutrient loads. Thus, we suggest
      that the calculation of flow-adjusted concentrations is a useful technique to aid
      in assessment of TMDL implementation.

PMID- 12785507
TI  - Greenhouse gas implications of household energy technology in Kenya.
AB  - Linkages between household energy technology, indoor air pollution, and
      greenhouse gas (GHG) emissions have become increasingly important in
      understanding the local and global environmental and health effects of domestic
      energy use. We report on GHG emissions from common Kenyan wood and charcoal
      cookstoves. Our estimations are based on 29 d of measurements under the
      conditions of actual use in 19 rural Kenyan households. Carbon monoxide (CO),
      particulate matter (PM10), combustion phase, and fuel mass were measured
      continuously or in short intervals in day-long monitoring sessions. Emissions of
      pollutants other than CO and PM10 were estimated using emissions ratios from
      published literature. We estimated that the daily carbon emissions from charcoal
      stoves (5202 +/- 2257 g of C: mean +/- SD) were lower than both traditional open
      fire (5990 +/- 1843 g of C) and improved ceramic woodstoves (5905 +/- 1553 g of
      C), but the differences were not statistically significant. However, when each
      pollutant was weighted using a 20-yr global warming potential, charcoal stoves
      emitted larger amounts of GHGs than either type of woodstove (9850 +/- 4600 g of
      C for charcoal as compared to 8310 +/- 2400 and 9649 +/- 2207 for open fire and
      ceramic woodstoves, respectively; differences not statistically significant). Non
      CO2 emissions from charcoal stoves were 5549 +/- 2700 g of C in 20-yr CO2
      equivalent units, while emissions were 2860 +/- 680 and 4711 +/- 919 for three
      stone fires and improved ceramic stoves, respectively, with statistically
      significant results between charcoal and wood stoves. Therefore in a sustainable
      fuel-cycle (i.e., excluding CO2), charcoal stoves have larger emissions than
      woodstoves. When the emissions from charcoal production, measured in a previous
      study, were included in the assessment, the disparity between the GHG emissions
      from charcoal and firewood increased significantly, with non-CO2 GHG emissions
      factors (g of C/kg of fuel burned) for charcoal production and consumption 6-13
      times higher than emissions from woodstoves. Policy implications and options for
      environment and public health are discussed.

PMID- 12785508
TI  - Assessment of the disposal of radioactive petroleum industry waste in
      nonhazardous landfills using risk-based modeling.
AB  - Certain petroleum production activities cause naturally occurring radioactive
      materials (NORM) to accumulate in concentrations above natural background levels,
      making safe and cost-effective management of such technologically enhanced NORM
      (TENORM) a key issue for the petroleum industry. As a result, both industry and
      regulators are interested in identifying cost-effective disposal alternatives
      that provide adequate protection of human health and the environment One such
      alternative, currently allowed in Michigan with restrictions, is the disposal of
      TENORM wastes in nonhazardous waste landfills. The disposal of petroleum industry
      wastes containing radium-226 (Ra-226) in nonhazardous landfills was modeled to
      evaluate the potential radiological doses and health risks to workers and the
      public. Multiple scenarios were considered in evaluating the potential risks
      associated with landfill operations and the future use of the property. The
      scenarios were defined, in part, to evaluate the Michigan policy; sensitivity
      analyses were conducted to evaluate the impact of key parameters on potential
      risks. The results indicate that the disposal of petroleum industry TENORM wastes
      in nonhazardous landfills in accordance with the Michigan policy and existing
      landfill regulations presents a negligible risk to most of the potential
      receptors considered in this study.

PMID- 12785509
TI  - Speciation and characterization of arsenic in Ketza River mine tailings using X
      ray absorption spectroscopy.
AB  - Ketza River mine tailings deposited underwater and those exposed near the
      tailings impoundment contain approximately 4 wt % As. Column-leaching tests
      indicated the potential for high As releases from the tailings. The tailings are
      composed dominantly of iron oxyhydroxides, quartz, calcite, dolomite, muscovite,
      ferric arsenates, and calcium-iron arsenates. Arsenopyrite and pyrite are trace
      constituents. Chemical compositions of iron oxyhydroxide and arsenate minerals
      are highly variable. The XANES spectra indicate that arsenic occurs as As(V) in
      tailings, but air-drying prior to analysis may have oxidized lower-valent As. The
      EXAFS spectra indicate As-Fe distances of 3.35-3.36 A for the exposed tailings
      and 3.33-3.35 A for the saturated tailings with coordination numbers of 0.96-1.11
      and 0.46-0.64, respectively. The As-Ca interatomic distances ranging from 4.15 to
      4.18 A and the coordination numbers of 4.12-4.58 confirm the presence of calcium
      iron arsenates in the tailings. These results suggest that ferric arsenates and
      inner-sphere corner sharing or bidentate-binuclear attachment of arsenate
      tetrahedra onto iron hydroxide octahedra are the dominant form of As in the
      tailings. EXAFS spectra indicate that the exposed tailings are richer in arsenate
      minerals whereas the saturated tailings are dominated by the iron oxyhydroxides,
      which could help explain the greater release of As from the exposed tailings
      during leaching tests. It is postulated that the dissolution of ferric arsenates
      during flow-through experiments caused the high As releases from both types of
      tailings. Arsenic tied to iron oxyhydroxides as adsorbed species are considered
      stable; however, iron oxyhydroxides having low Fe/As molar ratios may not be as
      stable. Continued As releases from the tailings are likely due to dissolution of
      both ferric and calcium-iron arsenates and desorption of As from high-As bearing
      iron oxyhydroxides during aging.

PMID- 12785510
TI  - Arsenic in groundwater in eastern New England: occurrence, controls, and human
      health implications.
AB  - In eastern New England, high concentrations (greater than 10 microg/L) of arsenic
      occur in groundwater. Privately supplied drinking water from bedrock aquifers
      often has arsenic concentrations at levels of concern to human health, whereas
      drinking water from unconsolidated aquifers is least affected by arsenic
      contamination. Water from wells in metasedimentary bedrock units, primarily in
      Maine and New Hampshire, has the highest arsenic concentrations-nearly 30% of
      wells in these aquifers produce water with arsenic concentrations greater than 10
      microg/L. Arsenic was also found at concentrations of 3-40 mg/kg in whole rock
      samples in these formations, suggesting a possible geologic source. Arsenic is
      most common in groundwater with high pH. High pH is related to groundwater age
      and possibly the presence of calcite in bedrock. Ion exchange in areas formerly
      inundated by seawater also may increase pH. Wells sampled twice during periods of
      1-10 months have similar arsenic concentrations (slope = 0.89; r-squared = 0.97).
      On the basis of water-use information for the aquifers studied, about 103,000
      people with private wells could have water supplies with arsenic at levels of
      concern (greater than 10 microg/L) for human health.

PMID- 12785511
TI  - Exposure to particulate matter, volatile organic compounds, and other air
      pollutants inside patrol cars.
AB  - People driving in a vehicle might receive an enhanced dose of mobile source
      pollutants that are considered a potential risk for cardiovascular diseases. The
      exposure to components of air pollution in highway patrol vehicles, at an
      ambient, and a roadside location was determined during 25 work shifts (3 p.m. to
      midnight) in the autumn of 2001, each day with two cars. A global positioning
      system and a diary provided location and activity information. Average pollutant
      levels inside the cars were low compared to ambient air quality standards: carbon
      monoxide 2.7 ppm, nitrogen dioxide 41.7 microg/m3, ozone 11.7 ppb, particulate
      matter smaller 2.5 microm (PM2.5) 24 microg/m3. Volatile organic compounds inside
      the cars were in the ppb-range and showed the fingerprint of gasoline. PM2.5 was
      24% lower than ambient and roadside levels, probably due to depositions
      associated with the recirculating air conditioning. Levels of carbon monoxide,
      aldehydes, hydrocarbons, and some metals (Al, Ca, Ti, V, Cr, Mn, Fe, Cu, and Sr)
      were highest in the cars, and roadside levels were higher than ambient levels.
      Elevated pollutant levels were related to locations with high traffic volumes.
      Our results point to combustion engine emissions from other vehicles as important
      sources of air pollutants inside the car.

PMID- 12785512
TI  - Polycyclic aromatic hydrocarbons in the air in the St. Lawrence Basin (Quebec).
AB  - High-volume air samples were collected from 1993 to 1996 in rural areas of Quebec
      to investigate on the levels and the vapor-particle partitioning of polycyclic
      aromatic hydrocarbons (PAHs). Ranges for the mean concentrations of total PAHs
      (ng m(-3)) were as follows: Villeroy, 3.31-18.92; St. Anicet, 7.57-22.84; and
      Mingan, 0.50-0.53. Lower molecular weight PAHs predominated at all locations.
      Particle-gas partition coefficients (Kp) were in good correlation with their
      vapor pressures (r2 = 0.79-0.97) with slopes deviating from the expected value of
      -1. The curve of the fractions of PAHs on particles in St Anicet in 1995 fell on
      that of Lake Superior. In St. Anicet, fractions of phenanthrene, fluoranthene,
      pyrene, and chrysene on particles were close to those calculated from the soot
      air partition coefficient (KSA). At all sites the mean ratios of particulate PAH
      of the same molecular weight but of very different reactivities were similar
      during the same sampling days, suggesting that particle-bearing PAHs in Villeroy
      and Mingan were of the same nature as those found in St. Anicet where adsorption
      onto soot particles was the major mechanism. Furthermore, the enthalpies of
      desorption for the predominant PAHs were close at all sites.

PMID- 12785513
TI  - Determination of phthalate ester congeners and mixtures by LC/ESI-MS in sediments
      and biota of an urbanized marine inlet.
AB  - Phthalate esters (PEs) are a group of widely used commercial chemicals consisting
      of many different congeners. Concentrations of di(2-ethylhexyl) phthalate ester
      in the parts per million range have been observed in sediments from locations in
      North America and Europe. However, sediment and biota concentrations of other
      widely used PEs (i.e., dibutyl phthalate, diisononyl phthalate, and diisodecyl
      phthalate) are rare and often in doubt because of analytical difficulties. One of
      the problems is that commercial formulations predominantly consist of PEs with a
      specific molecular weight but include many isomers within each molecular weight
      class. Currently there are no analytical methods or required standards to fully
      separate PEs into the different molecular weight classes corresponding to the
      formulations from which they originate. Hence, ambient total and mixture-specific
      PE concentrations do not exist. This study presents a new method based on
      reversed-phase liquid chromatography/ electrospray ionization mass spectrometry
      (LC/ESI-MS) for the quantitative determination of individual PEs, including six
      congeners on the U.S. EPA Priority pollutant list and several commercial PE
      isomeric mixtures, in complex environmental matrixes. The method is applied to
      determine the composition of PE concentrations in sediments and fish in an
      urbanized marine ecosystem. PE fingerprints in sediments show a predominance of
      high molecular weight PEs and match per capita consumption levels of PEs.
      Fingerprints in fish tissue show a predominance of low molecular weight PEs and
      do not match per capita consumption levels. The findings indicate that the higher
      molecular weight PEs are less biologically available than the lower molecular
      weight ones.

PMID- 12785514
TI  - Aerosol-bound emissions of polycyclic aromatic hydrocarbons and sterols from
      aeration tanks of a municipal waste water treatment plant.
AB  - Aeration tanks of wastewater treatment plants (WWTP) are a potential source of
      atmospheric aerosol particles. Several groups of organic compounds (sterols,
      polycyclic aromatic hydrocarbons, estrogens) were analyzed in aerosol particles
      sampled at a municipal WWTP, and the particle size distribution was measured
      directly with optical particle counters. Aerosol emissions from an activated
      treatment tank equipped with fine bubble diffusers were low; however, at the
      preaeration tank equipped with coarse bubble diffusers, sterol concentrations up
      to 14 ng m(-3) were measured. Directly next to the tank, sterols were associated
      mainly to particles with aerodynamic diameter >1.35 microm. The results suggest
      that coprostanol could be a useful tracer for monitoring the emission of aerosol
      particles from WWTPs. Moreover, wastewater treatment could contribute
      substantially to the atmospheric concentrations of cholesterol and 24
      ethylcholesterol. Aeration tanks with fine bubble diffusers are no major source
      of atmospheric aerosol particles, whereas coarse bubbling devices seem to emit
      considerable amounts of aerosol particles.

PMID- 12785515
TI  - Automated measurements of ammonia and nitric acid in indoor and outdoor air.
AB  - Simultaneous temporally resolved indoor and outdoor measurements of ammonia and
      nitric acid are valuable for determining the gas-particle equilibrium conditions
      governing concentrations of ammonium nitrate aerosol. We report the results of
      simultaneous automated indoor and outdoor measurements of ammonia and nitric acid
      concentrations made at an unoccupied, single-story residence in Clovis, CA during
      three periods from October 2000 to January 2001. The measurements were conducted
      as part of a controlled study to explore mechanisms governing indoor
      concentrations of fine aerosols of outdoor origin. The gas-phase measurements
      were performed using diffusion denuders and ion chromatography with 30 min
      temporal resolution and detection limits below 1 ppb. The conditions of the field
      experiment span a wide range of outdoor climate as well as natural and forced
      indoor conditions. During all periods ammonia concentrations were generally
      slightly higher indoors than out, with both outdoor and indoor concentrations
      varying in a range from approximately 5 to 30 ppb. Nitric acid was only detected
      in outdoor air in October 2000, at concentrations up to 3 ppb. During the October
      period, the product of outdoor nitric acid and ammonia concentrations sometimes
      deviated from that expected for equilibrium between gas and ammonium nitrate
      particulate phases and the degree and direction of disequilibrium were correlated
      with trends in air temperature. The consistently low indoor concentrations of
      nitric acid were not consistent with equilibrium between gas and particle phases
      and suggest that a combination of low penetration into the building and a high
      loss rate for nitric acid reduce indoor concentrations significantly below those
      outdoors.

PMID- 12785516
TI  - Environmental, mineralogical, and genetic characterization of ochreous and white
      precipitates from acid mine drainages in Taebaeg, Korea.
AB  - X-ray diffraction, energy-dispersive X-ray fluorescence, thermal analysis,
      scanning electron microscopy, inductively coupled plasma emission spectroscopy,
      and ion chromatography were used for the environmental, mineralogical, and
      genetic characterization of brownish yellow, reddish brown, and white
      precipitates from acid mine drainage in Taebaeg, Korea. Ferrihydrite+goethite,
      schwertmannite, and Al-sulfate were precipitated under different chemical
      environments on the stream bottom of acid mine drainages. The brownish yellow
      precipitates (Munsell color 9.5YR hues) consist mainly of schwertmannite with
      traces of quartz, illite, pyrophyllite, goethite, lepidocrocite, and gypsum. The
      reddish brown precipitates (Munsell color 3.5YR hues) consist mainly of
      ferrihydrite with small amount of goethite. The white precipitates consist mainly
      of poorly crystalline Al-sulfate with small amounts of quartz, gypsum, and
      calcite. Thermal decomposition due to dehydration of ferrihydrite and
      schwertmannite takes place at approximately 120 degrees C and 140 degrees C,
      respectively. Al-sulfate converts to gamma-alumina at 850 degrees C. SEM study
      shows that the spheroid and rod-shaped precipitates characteristic of Gallionella
      consist of iron hydroxide with varying chemical compositions.

PMID- 12785517
TI  - Small-volume releases of gasoline in the vadose zone: impact of the additives
      MTBE and ethanol on groundwater quality.
AB  - A controlled gasoline spill experiment was performed under outdoor conditions
      typical for winter in temperate regions to study the fate of methyl tert-butyl
      ether (MTBE), ethanol, benzene, and selected other petroleum hydrocarbons.
      Artificial gasoline containing MTBE and ethanol (5% w/w of each) was placed at a
      defined depth into a 2.3 m thick unsaturated zone of alluvial sand overlying a
      gravel aquifer in a lysimeter. During an initial period of 41 days without
      recharge, MTBE and hydrocarbon vapors migrated by vapor-phase diffusion to
      groundwater, while ethanol vapors were naturally attenuated. In a subsequent
      period of 30 days with 5-mm daily recharge, all soluble compounds including
      ethanol were transported to the groundwater. Ethanol disappeared concomitantly
      with benzene and all other petroleum hydrocarbons except isooctane from the
      aerobic groundwater due to biodegradation. MTBE persisted for longer than 6
      months at concentrations larger than 125000 microg L(-1). No evidence for MTBE
      biodegradation was found, whereas > 99.6% of ethanol removal from the lysimeter
      was due to biodegradation. It is concluded that MTBE-free gasoline would be less
      harmful for groundwater resources and that ethanol is an acceptable substitute.

PMID- 12785518
TI  - Quantitative evaluation of the synergistic sequential inactivation of Bacillus
      subtilis spores with ozone followed by chlorine.
AB  - This investigation of sequential disinfection, with ozone followed by free
      chlorine, was carried out using Bacillus subtilis spores, to make a quantitative
      evaluation and to improve the mechanistic understanding of their synergistic
      effect. This study shows that the extent of the synergistic effect in the
      inactivation of Bacillus subtilis spores appears to be dependent upon the level
      of preozonation. However, when the ozone pretreatment level exceeded the lag
      phase of the ozone inactivation curve, the chlorine inactivation curves were
      almost identical regardless of the level of preozonation. When this sequential
      disinfection was performed in the reverse order, no enhanced disinfection was
      observed. This difference, depending on the order of disinfectant application in
      sequential disinfection, was explained in terms of the enhanced disinfection
      being the result of the greater intracellular diffusion of free chlorine, caused
      by the cell surface disruption induced by ozone. The practical implications of
      this synergistic sequential inactivation with ozone followed by free chlorine
      were discussed, along with the issue of selecting the amount of each oxidant to
      use in water treatment plants, to achieve a specific level of microorganism
      inactivation.

PMID- 12785519
TI  - Fate and effects of azinphos-methyl in a flow through wetland in South Africa.
AB  - Our knowledge about the effectiveness of constructed wetlands in retaining
      agricultural nonpoint-source pesticide pollution is limited. A 0.44-ha vegetated
      wetland built along a tributary of the Lourens River, Western Cape, South Africa,
      was studied to ascertain the retention, fate, and effects of spray drift-borne
      azinphos-methyl (AZP). Composite water samples taken at the inlet and outlet
      during five spray drift trials in summer 2000 and 2001 revealed an overall
      reduction of AZP levels by 90 +/- 1% and a retention of AZP mass by 61 +/- 5%.
      Samples were collected at the inlet outlet, and four platforms within the wetland
      to determine the fate and effect of AZP in the wetland after direct spray drift
      deposition in the tributary 200 m upstream of the inlet. Peak concentrations of
      AZP decreased, and the duration of exposure increased from inlet (0.73 microg/L;
      9 h) via platforms 1 and 4 to outlet (0.08 microg/L; 16 h). AZP sorbed to plants
      or plant surfaces, leading to a peak concentration of 6.8 microg/kg dw. The
      living plant biomass accounted for 10.5% of the AZP mass initially retained in
      the wetland, indicating processes such as volatilization, photolysis, hydrolysis,
      or metabolic degradation as being very important AZP was not detected in
      sediments. Water samples taken along two 10-m transects situated perpendicular to
      the shore indicated a homogeneous horizontal distribution of the pesticide: 0.23
      +/- 0.02 and 0.14 +/- 0.04 microg/L (n = 5), respectively. Both Copepoda (p =
      0.019) and Cladocere (p = 0.027) decreased significantly 6 h postdeposition and
      remained at reduced densities for at least 7 d. In parallel, the chlorophyll a
      concentration showed an increase, although not significant, within 6 h of spray
      deposition. The study highlights the potential of constructed wetlands as a risk
      mitigation strategy for spray drift-related pesticide pollution.

PMID- 12785520
TI  - Temperature-dependent effects of cadmium on Daphnia magna: accumulation versus
      sensitivity.
AB  - Standard toxicity tests are performed at one constant, optimal temperature
      (usually 20 degrees C), while in the field variable and suboptimal temperatures
      may occur. Lack of knowledge on the interactions between chemicals and
      temperature hampers the extrapolation of laboratory toxicity data to ecosystems.
      Therefore, the aim of this study was to analyze the effects of temperature on
      cadmium toxicity to the waterflea Daphnia magna and to address possible processes
      responsible for temperature-dependent toxicity. This was investigated by
      performing standard toxicity tests with D. magna under a wide temperature range.
      Thermal effects on accumulation kinetics were determined by estimating uptake and
      elimination rates from accumulation experiments. To study temperature dependency
      of the intrinsic sensitivity of the daphnids to cadmium, the DEBtox model was
      used to estimate internal threshold concentrations (ITCs) and killing rates from
      the toxicity and accumulation data. The results revealed that increasing
      temperature lowered the ITC and increased the killing rate and the uptake rate of
      the metal. Enhanced sensitivity of D. magna was shown to be the primary factor
      for temperature-dependent toxicity. Since temperature has such a major impact on
      toxicity, a temperature correction may be necessary when translating toxicity
      data from the laboratory to the field.

PMID- 12785521
TI  - Microbial mercury transformation in anoxic freshwater sediments under iron
      reducing and other electron-accepting conditions.
AB  - Potential rates of microbial methylation of inorganic mercury (added as HgCl2)
      and degradation of methyl mercury (MeHg) (added as CH3HgCl) were investigated in
      anoxic sediments from the Mobile Alabama River Basin (MARB) dominated by
      different terminal electron-accepting processes (TEAPs). Potential rates of
      methylation were comparable under methanogenic and sulfate-reducing conditions
      but suppressed under iron-reducing conditions, in slurries of freshwater wetland
      sediment In contrast, MeHg degradation rates were similar under all three TEAPs.
      Microbial Hg methylation and MeHg degradation were also investigated in surface
      sediment from three riverine sites, two of which had iron reduction and one
      sulfate reduction, as the dominant TEAP (as determined by 14C-acetate metabolism
      and other biogeochemical measurements). Methylation was active in sulfate
      reducing sediments of a tributary creek and suppressed in iron-reducing, sandy
      sediments from the open river, whereas MeHg degradation was active at all three
      sites. Although iron-reducing conditions often suppressed methylation, some
      methylation activity was observed in two out of three replicates from iron
      reducing sediments collected near a dam. Given that MeHg degradation was
      consistently observed under all TEAPs, our results suggest that the net flux of
      MeHg from iron-reducing surface sediments may be suppressed (due to inhibition of
      gross MeHg production) compared to sediments supporting other TEAPs.

PMID- 12785522
TI  - Speciation of Pb(II) sorbed by Burkholderia cepacia/goethite composites.
AB  - Bacterial-mineral composites are important in the retention of heavy metals such
      as Pb due to their large sorption capacity under a wide range of environmental
      conditions. However, the partitioning of heavy metals between components in such
      composites is not probed directly. Using Burkholderia cepacia biofilms coated
      with goethite (alpha-FeOOH) particles, the partitioning of Pb(II) between the
      biological and iron-(oxyhydr)oxide surfaces has been measured using an X-ray
      spectroscopic approach. EXAFS spectra were fit to quantitatively determine the
      fraction of Pb(II) associated with each component as a function of pH and [Pb].
      At pH < 5.5, at least 50% of the total sorbed Pb(II) is associated with the
      biofilm component, whereas the total uptake within the composite is dominated by
      goethite (> 70% Pb/goethite) above pH 6. Direct comparison can be made between
      the amount of Pb(II) bound to each component in the composite vs separate binary
      systems (i.e., Pb/biofilm or Pb/goethite). At high pH, Pb(II) uptake on the
      biofilm is dramatically decreased due to competition with the goethite surface.
      In contrast, Pb uptake on goethite is significantly enhanced at low pH (2-fold
      increase at pH 5) compared to systems with no complexing ligands. The mode of
      Pb(II)-binding to the goethite component changes from low to high [Pb].
      Structural fitting of the EXAFS spectra collected from 10(-5.6) to 10(-3.6) M
      [Pb]eq at pH 6 shows that the Pb-goethite surface complexes at low [Pb] are
      dominated by inner-sphere bidentate, binuclear complexes bridging two adjacent
      singly coordinated surface oxygens, giving rise to Pb-Fe distances of
      approximately 3.9 A. At high [Pb], the dominant Pb(II) inner-sphere complexes on
      the goethite surface shift to bidentate edge-sharing complexes with Pb-Fe
      distances of approximately 3.3 A.

PMID- 12785523
TI  - Role of lipopolysaccharides in the adhesion, retention, and transport of
      Escherichia coli JM109.
AB  - The role of lipopolysaccharides (LPS) in bacterial adhesion was investigated via
      atomic force microscopy (AFM). Adhesion between a silicon nitride tip and
      Escherichia coli JM109 was measured in water and 0.01 M phosphate-buffered saline
      (PBS) on untreated cells and on a sample of E. coli treated with 100 mM
      ethylenediaminetetraacetic acid (EDTA), which removes approximately 80% of the
      LPS molecules. LPS removal decreased the adhesion affinity between the bacterial
      cells and the AFM tip from -2.1 +/- 1.8 to -0.40 +/- 0.36 nN in water and from 
      0.74 +/- 0.44 to -0.46 +/- 0.23 nN in 0.01 M PBS (statistically different, Mann
      Whitney rank sum test, P < 0.01). The distributions of adhesion affinities
      between E. coli LPS macromolecules and the AFM tip could be described by gamma
      distribution functions. Direct measurements of the adhesive force between E. coil
      and a surface were compared with adhesion in batch and column experiments, and
      agreement was observed between the influences of LPS on adhesion in each system.
      Bacterial batch retention to glass or in packed beds to quartz sand decreased
      after LPS removal. When interaction forces were measured during the approach of
      the AFM tip to a bacterium, steric repulsive forces were seen for both treated
      and untreated cells, but the repulsion was greater when the LPS was intact A
      model for steric repulsion predicted a reduction of the equilibrium length of the
      surface polymers from 242 to 64 nm in water and from 175 to 81 nm in buffer,
      after removal of a portion of the LPS. DLVO calculations based on conventional
      and soft-particle DLVO theories predicted higher energy barriers to adhesion for
      all surfaces after LPS removal, consistent with experimental findings. Adhesion
      forces between the AFM tip and bacterial polymers were correlated with bacterial
      attachment and retention, while measurements of interaction forces during the
      approach of the AFM tip to the bacterium did not correlate with subsequent
      adhesion behavior to glass or quartz sand.

PMID- 12785524
TI  - EXAFS study of Sn(IV) immobilization by hardened cement paste and calcium
      silicate hydrates.
AB  - In this study, the immobilization mechanisms of Sn(IV) onto calcium silicate
      hydrates (C-S-H) and hardened cement paste (HCP) have been investigated by
      combining wet chemistry experiments with X-ray absorption spectroscopy (XAS).
      Evidence is presented which demonstrates the formation of a Sn(IV) inner-sphere
      surface complex on C-S-H with a CaO/SiO2 weight ratio of 0.7. Two possible
      structural models, implying a corner sharing between the Sn octahedra and Q1 or
      Q2b Si tetrahedra, have been developed based on the experimentally determined
      structural parameters. In HCP, the formation of a different type of Sn(IV) inner
      sphere complex has been observed, indicating that C-S-H may not be the uptake
      controlling phase for Sn(IV) in the cement matrix. An alternative structural
      model for Sn(IV) binding in HCP has been developed, assuming that ettringite is
      the uptake-controlling phase. At high Sn(IV) concentrations, Sn(IV)
      immobilization in HCP occurs due to the formation of CaSn(OH)6.

PMID- 12785525
TI  - Oxidation of H2S by iron oxides in unsaturated conditions.
AB  - Previous studies have demonstrated that gas-phase H2S can immobilize certain
      redox-sensitive contaminants (e.g., Cr, U, Tc) in vadose zone environments. A key
      issue for effective and efficient delivery of H2S in these environments is the
      reactivity of the gas with indigenous iron oxides. To elucidate the factors that
      control the transport of H2S in the vadose zone, laboratory column experiments
      were conducted to identify reaction mechanisms and measure rates of H2S oxidation
      by iron oxide-coated sands using several carrier gas compositions (N2, air, and
      O2) and flow rates. Most experiments were conducted using ferrihydrite-coated
      sand. Additional studies were conducted with goethite- and hematite-coated sand
      and a natural sediment. Selective extractions were conducted at the end of each
      column experiment to determine the mass balance of the reaction products. XPS was
      used to confirm the presence of the reaction products. For column experiments in
      which ferrihydrite-coated sand was the substrate and N2 was the carrier gas, the
      major H2S oxidation products were FeS and elemental sulfur (mostly S8(0),
      represented as S(0) for simplicity) at ratios that were consistent with the
      stoichiometry of the postulated reactions. When air or O2 were used as the
      carrier gas, S(0) became the dominant reaction product along with FeS2 and
      smaller amounts of FeS, sulfate, and thiosulfate. A mathematical model of
      reactive transport was used to test the hypothesis that S(0) forming on the iron
      oxide surfaces reduces access of H2S to the reactive surface. Several conceptual
      models were assessed in the context of the postulated reactions with the final
      model based on a linear surface poisoning model and fitted reaction rates. These
      results indicate that carrier gas selection is a critical consideration with
      significant tradeoffs for remediation objectives.

PMID- 12785526
TI  - Linking cesium and strontium uptake to kaolinite weathering in simulated tank
      waste leachate.
AB  - Weathering behavior of kaolinite was studied in batch systems under geochemical
      conditions characteristic of tank waste released to the vadose zone at the
      Hanford Site, WA (0.05 M Al(T), 2 M Na+, 1 M N03-, pH approximately 14, Cs+ and
      Sr2+ present as co-contaminants). Time series experiments were conducted from 0
      to 369 d, with initial Cs+ and Sr2+ concentrations ranging from 10(-5) to 10(-3)
      M. Dissolution of kaolinite increased soluble Si and Al to maximum levels at 7 d
      (Cs and Sr concentrations of 10(-5) and 10(-4) M) or 33 d (Cs and Sr
      concentrations of 10(-3) M). Subsequent precipitation of Si and Al was coupled to
      the formation of oxalate-extractable solids that incorporated Cs and Sr.
      Strontium sorption was nearly complete within 24 h for initial Sr concentrations
      (Sr0) < or = 10(-4) whereas Cs uptake increased over the full year of the
      experiment for all initial Cs concentrations. Spectroscopic analyses revealed
      neoformed solids including the zeolite Na-Al silicate (Al-chabazite), and
      feldspathoids sodium aluminum nitrate silicate (NO3-sodalite), and sodium
      aluminum nitrate silicate hydrate (NO3-cancrinite), which can incorporate Cs.
      Single-pulse 27Al solid-state nuclear magnetic resonance (NMR)
      spectroscopyyielded first-order rate constants (k)for mineral transformation that
      decreased from 3.5 x 10(-3) to 2 x 10(-3) d(-1) as Cs and Sr concentrations were
      increased from 10(-5) to 10(-3) M. Discrete strontium silicate solids were also
      observed. The incongruent dissolution of kaolinite promoted the sequestration of
      contaminants into increasingly recalcitrant solid phases over the 1-yr time
      period.

PMID- 12785527
TI  - PCB and PAH speciation among particle types in contaminated harbor sediments and
      effects on PAH bioavailability.
AB  - This research provides particle-scale understanding of PCB and PAH distribution
      in sediments obtained from three urban locations in the United States: Hunters
      Point, CA; Milwaukee Harbor, WI; and Harbor Point, NY. The sediments comprised
      mineral grains (primarily sand, silt, and clays) and carbonaceous particles
      (primarily coal, coke, charcoal, pitch, cenospheres, and wood). The carbonaceous
      sediment fractions were separated from the mineral fractions based on their lower
      density and were identified by petrographic analysis. In all three sediments,
      carbonaceous particles contributed 5-7% of the total mass and 60-90% of the PCBs
      and PAHs. The production of carbonaceous particles is not known to be associated
      with PCB contamination, and it is very unlikely that these particles can be the
      source of PCBs in the environment Thus, it appears that carbonaceous particles
      preferentially accumulate PCBs acting as sorbents in the aqueous environment if
      PCBs are released directly to the sediment or if deposited as airborne soot
      particles. Aerobic bioslurry treatment resulted in negligible PAH loss from the
      carbonaceous coal-derived material in Milwaukee Harbor sediment but resulted in
      80% of the PAHs being removed from carbonaceous particles in Harbor Point
      sediment. Microscale PAH extraction and analysis revealed that PAHs in Harbor
      Point sediment were associated mainly with coal tar pitch residue. PAHs present
      in semisolid coal tar pitch are more bioavailable than PAHs sorbed on
      carbonaceous particles such as coal, coke, charcoal, and cenosphere. Results of
      this study illustrate the importance of understanding particle-scale association
      of hydrophobic organic contaminants for explaining bioavailability differences
      among sediments.

PMID- 12785528
TI  - Atmospheric chemistry of nonanal.
AB  - During the Southern Oxidants Study 1999 field campaign at Dickson, TN, we
      conducted measurements of the n-aldehydes propanal, pentanal, hexanal, heptanal,
      octanal, and nonanal. Propanal and nonanal tended to have the largest
      concentrations, with afternoon maxima of approximately 0.3 ppb. These aldehydes
      typically represented a significant fraction of the VOC reactivity defined as
      k(OH)[VOC]. However, this information is misleading with regard to the impact of
      these aldehydes on ozone formation, as their oxidation can represent a
      significant NOx sink. Motivated by the relatively large nonanal concentrations,
      we conducted a laboratory study of the products of the nonanal + OH reaction. The
      OH + nonanal reaction rate constant was determined via the relative rate
      technique and found to be 3.6 (+/- 0.7) x 10(-11) cm3 molecule(-1) s(-1). Under
      conditions of high [NO2]/[NO], we determined that 50 +/- 6% of OH-nonanal
      reaction occurs via abstraction of the aldehydic H-atom through measurement of
      the peroxynonanyl nitrate yield. We also studied the production of organic
      nitrates from OH reaction with nonanal in the presence of NO. As expected, a
      major product (20% at large [NO]/[NO2]) of this reaction was 1-nitrooxy octane.
      We calculate that the branching ratio for 1-nitrooxy octane formation from
      peroxyoctyl radicals is 0.40 +/- 0.05. On the basis of these measurements, we
      find that for more than 50% of the time OH reacts with nonanal (for midday summer
      conditions) an organic nitrate or PAN compound is formed, making this important
      atmospheric aldehyde an effective NOx sink.

PMID- 12785529
TI  - Continuous analysis of dissolved gaseous mercury (DGM) and mercury flux in two
      freshwater lakes in Kejimkujik Park, Nova Scotia: evaluating mercury flux models
      with quantitative data.
AB  - Diurnal patterns for dissolved gaseous mercury (DGM) concentration, mercury flux,
      several water variables (pH, oxidation reduction potential (ORP), water
      temperature), and meteorological variables (wind speed, air temperature, %
      relative humidity, solar radiation) were measured in two lakes with contrasting
      dissolved organic carbon (DOC) concentrations in Kejimkujik Park, Nova Scotia. A
      continuous analysis system made it possible to measure quick changes in DGM over
      time. Consistently higher DGM concentrations were found in the high DOC lake as
      compared to the low DOC lake. An examination of current mercury flux models using
      this quantitative data indicated some good correlations between the date and
      predicted flux (r ranging from 0.27 to 0.83) but generally poor fit (standard
      deviation of residuals ranging from 0.97 to 3.39). Cross-correlation analysis
      indicated that DGM dynamics changed in response to solar radiation with lag-times
      of 65 and 90 min. This relationship with solar radiation was used to develop new
      predictive models of DGM and mercury flux dynamics for each lake. We suggest that
      a generalized approach using time-shifted solar radiation date to predict DGM can
      be incorporated into existing mercury flux models. It is clear from the work
      presented that DOC and wind speed may also play important roles in DGM and
      mercury flux dynamics, and these roles have not been adequately accounted for in
      current predictive models.

PMID- 12785530
TI  - Uptake and depuration of 4-nonylphenol by the benthic invertebrate Gammarus
      pulex: how important is feeding rate?
AB  - The major exposure and uptake route for soluble toxins by aquatic organisms is
      generally considered to be through the water column. In the case of hydrophobic
      chemicals, exposure and uptake through diet often take on greater importance as
      the chemicals adsorb onto organic sediments and food. A chemical that has
      recently come under close scrutiny because of its toxicity and possible endocrine
      disrupting effects in aquatic life is 4-nonylphenol (NP). It has been detected in
      environmental water and sediment samples and is a persistent and hydrophobic (log
      KOW = 4.48) contaminant in many aquatic systems. In this study, the relative
      importance of NP uptake through accumulation from diet and water was examined for
      the detritus-feeding freshwater shrimp Gammarus pulex. Using a bootstrap
      nonlinear regression technique, the level of toxin present in G. pulex at any
      time during or after initial exposure was estimated. Heterogeneity, together with
      assumptions on feeding rate, was shown to affect the determination of NP uptake
      substantially. Because of its lifestyle as a benthic organism, the main exposure
      route was at first assumed to be through sediments and food. However, the results
      suggest that major uptake may also occur through water. The statistical and
      modeling methodology may be applied to uptake and depuration assessments for any
      aquatic organisms exhibiting a variable feeding phase.

PMID- 12785531
TI  - Modeling colloid attachment, straining, and exclusion in saturated porous media.
AB  - A conceptual model for colloid transport is developed that accounts for colloid
      attachment straining, and exclusion. Colloid attachment and detachment is modeled
      using first-order rate expressions, whereas straining is described using an
      irreversible first-order straining term that is depth dependent. Exclusion is
      modeled by adjusting transport parameters for colloid-accessible pore space.
      Fitting attachment and detachment model parameters to colloid transport data
      provided a reasonable description of effluent concentration curves, but the
      spatial distribution of retained colloids at the column inlet was severely
      underestimated for systems that exhibited significant colloid mass removal. A
      more physically realistic description of the colloid transport data was obtained
      by simulating both colloid attachment and straining. Fitted straining
      coefficients were found to systematically increase with increasing colloid size
      and decreasing median grain size. A correlation was developed to predict the
      straining coefficient from colloid and porous medium information. Numerical
      experiments indicated that increasing the colloid excluded volume of the pore
      space resulted in earlier breakthrough and higher peak effluent concentrations as
      a result of higher pore water velocities and lower residence times, respectively.
      Velocity enhancement due to colloid exclusion was predicted to increase with
      increasing exclusion volume and increasing soil gradation.

PMID- 12785532
TI  - Modeling controlled nutrient release from polymer coated fertilizers: diffusion
      release from single granules.
AB  - A comprehensive model describing the complex and "non-Fickian" (mathematically
      nonlinear) nature of the release from single granules of membrane coated,
      controlled release fertilizers (CRFs) is proposed consisting of three stages: i.
      a lag period during which water penetrates the coating of the granule dissolving
      part of the solid fertilizer in it ii. a period of linear release during which
      water penetration into and release out occur concomitantly while the total volume
      of the granules remains practically constant; and iii. a period of "decaying
      release", starting as the concentration inside the granule starts to decrease. A
      mathematical model was developed based on vapor and nutrient diffusion equations.
      The model predicts the release stages in terms of measurable geometrical and
      chemophysical parameters such as the following: the product of granule radius and
      coating thickness, water and solute permeability, saturation concentration of the
      fertilizer, and its density. The model successfully predicts the complex and
      "sigmoidal" pattern of release that is essential for matching plant temporal
      demand to ensure high agronomic and environmental effectiveness. It also lends
      itself to more complex statistical formulations which account for the large
      variability within large populations of coated CRFs and can serve for further
      improving CRF production and performance.

PMID- 12785533
TI  - Modeling controlled nutrient release from a population of polymer coated
      fertilizers: statistically based model for diffusion release.
AB  - A statistically based model for describing the release from a population of
      polymer coated controlled release fertilizer (CRF) granules by the diffusion
      mechanism was constructed. The model is based on a mathematical-mechanistic
      description of the release from a single granule of a coated CRF accounting for
      its complex and nonlinear nature. The large variation within populations of
      coated CRFs poses the need for a statistically based approach to integrate over
      the release from the individual granules within a given population for which the
      distribution and range of granule radii and coating thickness are known. The
      model was constructed and verified using experimentally determined parameters and
      release curves of polymer-coated CRFs. A sensitivity analysis indicated the
      importance of water permeability in controlling the lag period and that of solute
      permeability in governing the rate of linear release and the total duration of
      the release. Increasing the mean values of normally distributed granule radii or
      coating thickness, increases the lag period and the period of linear release. The
      variation of radii and coating thickness, within realistic ranges, affects the
      release only when the standard deviation is very large or when water permeability
      is reduced without affecting solute permeability. The model provides an effective
      tool for designing and improving agronomic and environmental effectiveness of
      polymer-coated CRFs.

PMID- 12785534
TI  - Partiton-controlled delivery of toxicants: a novel in vivo approach for embryo
      toxicity testing.
AB  - In conventional static or semi-static embryo toxicity assays with fish, the
      nominal concentrations of hydrophobic chemicals are often used to establish the
      toxic thresholds, which often far exceed the solubility limits of test compounds.
      Saturators and continuous-flow diluters have been used to provide stable
      concentrations below solubility but are complex, use large amounts of test
      substance, and produce large volumes of waste. We present a partition-controlled
      delivery (PCD) method that maintains the concentrations of chemicals in test
      solutions at or below solubility limits for extended exposure times.
      Concentrations are maintained by equilibrium partitioning of test chemicals from
      a series of poly(dimethylsiloxane) films loaded with a range of concentrations of
      each chemical. The efficacy of the PCD assay was tested by comparisons with
      static (no renewal) and semi-static (24-h renewal) embryo-larval toxicity tests.
      The test species was Japanese medaka (Oryzias latipes) exposed to retene (7
      isopropyl-1-methylphenanthrene), a compound causing blue sac disease (BSD) in
      fish embryos. In the PCD assay, the median effective concentration (EC50) for BSD
      was 10 microg/L, below retene's solubility of 17 microg/L. In contrast, the
      nominal EC50 values for the semi-static 24-h and static assays were about 10 (150
      microg/L) and 150 times (2500 microg/L) greater than solubility, respectively.
      The PCD method is a more sensitive and realistic method for assessing toxicity of
      nonpolar compounds than (semi)-static assays.

PMID- 12785535
TI  - Accuracy of continuous ice-core trace-element analysis by inductively coupled
      plasma sector field mass spectrometry.
AB  - Trace elements trapped in glaciers are important indicators for the
      characterization of past biogeochemical cycles, the identification of numerous
      sources and their varying strength, and thus indirectly provide insight into past
      climate variations. However, this necessitates highly resolved and continuous
      records of trace elements in ice. To obtain records corresponding to these
      requirements, a continuous ice-core melting (CIM) device was coupled to an
      inductively coupled plasma sector field mass spectrometer (ICP-SFMS). Accuracy of
      this newly developed method was tested by replicate analysis of longitudinally
      cut ice-core sections (reproducibility) and by comparing results of the
      continuous method with the conventional decontamination and analysis procedure.
      The new, fast method is suited to accurately determine concentrations of a number
      of elements, such as Li, Na, Mg, Ca, Mn, Co, Br, Sr, Mo, and Tl. However, for 18
      elements (including Al and lanthanides) observed concentrations were
      underestimated when analyzed using the continuous method. Possible explanations
      of these low concentrations are (i) incomplete dissolution of mineral dust
      particles contained in the ice resulting from a delayed acidification step and/or
      (ii) adsorption of dissolved trace elements or mineral dust particles on the
      surface of the ice melting device.

PMID- 12785536
TI  - High-resolution gas chromatography retention data as basis for the estimation of
      KOW values using PCB congeners as secondary standards.
AB  - We estimated KOW values that are usually derived by liquid chromatography solely
      from gas chromatographic (GC) data by selective correlation with PCB congeners as
      secondary standards. The GC method was established and validated with literature
      known values obtained with other methods. Twenty-seven chlorinated diphenyl
      ethers (PCDE), 19 chlorinated naphthalenes (PCN), 4,4'-DDE, and three brominated
      diphenyl ethers (PBDE) were used for method validation. The advantages of our
      method are that only amounts in the nanogram range or less are needed, complex
      mixtures can be analyzed, KOW values of isomers can be determined, and even the
      exact structure of compounds does not have to be known. The quality of the KOW
      values obtained by the GC method mainly depends on the accuracy of the data of
      the compounds used as standards for the correlation. These data should be based
      on reliable experimental methods. Our semi-experimental approach in approximating
      physicochemical data relevant to the environmental distribution--vapor pressure
      of subcooled liquid and log KOW--can be extended to further classes of compounds
      because normalized GC retention data are easily available. We exemplified our
      approach with a bioaccumulating naturally occurring heptachlorinated 1-methyl
      1',2-bipyrrole, which is highly abundant in fish from the South Atlantic among
      others.

PMID- 12785537
TI  - Photodecomposition of carbaryl in the presence of silver-doped zeolite Y and
      Suwannee River natural organic matter.
AB  - The synthesis and characterization of a novel catalyst for the photodecomposition
      of carbaryl (1-naphthyl, N-methylcarbamate) is reported. In the absence of a
      catalyst, but in the presence of UV light a 30 ppm solution of carbaryl
      decomposes with a first-order rate constant of (5.6 +/- 0.3) x 10(-5) s(-1) (298
      K) and a quantum efficiency of 4.8 x 10(-3) molecules/photon. In the presence of
      the Ag-zeolite Y catalyst with 2.42% Ag by weight, the photodecomposition rate
      becomes 80 times faster. The addition of Suwannee River natural organic matter
      (NOM), which can inactivate photocatalysts, has a minimal effect on this system.
      In the presence of three different concentrations of NOM and 30 ppm carbaryl, our
      results indicate that the NOM increases or decreases the catalytic
      photodecomposition rate by only a factor of 3 at most.

PMID- 12785538
TI  - Granulated activated carbon modified with hydrophobic silica aerogel-potential
      composite materials for the removal of uranium from aqueous solutions.
AB  - Aqueous solutions of 100 parts per billion (ppb) uranium at pH 7 were treated
      with granulated activated carbon (GAC) that had been modified with various
      formulations of hydrophobic aerogels. The composite materials were found to be
      superior in removing uranium from a stock solution compared to GAC alone
      evaluated by a modified ASTM D 3860-98 method for batch testing. The testing
      results were evaluated using a Freundlich adsorption model. The best performing
      material has parameters of n = 287 and Kf = 1169 compared to n = 1.00, and Kf =
      20 for GAC alone. The composite materials were formed by mixing (CH3O)4Si with
      the hydrophobic sol-gel precursor, (CH3O)3SiCH2CH2CF3 and with specified
      modifiers, such as H3PO4, Ca(NO3)2, and (C2H5O)3SiCH2CH2P(O)(OC2H5)2, elation
      catalysts, and GAC in a supercritical reactor system. After gelation,
      supercritical extraction, and sieving, the composites were tested.
      Characterization by FTIR and 31P NMR indicate the formation of phosphate in the
      case of the H3PO4 and Ca(NO3)2 composites and phosphonic acid related compounds
      in the phosphonate composite. These composite materials have potential
      application in the clean up of groundwater at DOE and other facilities.

PMID- 12785539
TI  - Complete degradation of perchlorate in ferric chloride and hydrochloric acid
      under controlled temperature and pressure.
AB  - Despite favorable thermodynamics, the reduction of perchlorate (ClO4-) is
      kinetically limited in aqueous media because of its high activation energy. In
      this paper, a new methodology has been presented for degrading ClO4- in an FeCl3
      HCl solution at an elevated temperature (< 200 degrees C) and/or pressure
      (approximately 20 atm). Results indicate that the rate constant for the pseudo
      first-order reaction between ClO4- and ferrous Fe(II) (in excess) increased
      nearly 3 orders of magnitude when the temperature was increased from 110 to 195
      degrees C, and a complete reduction of ClO4- occurred in < 1 h at 195 degrees C
      in the FeCl3-HCl solution. The activation energy of the reaction was calculated
      to be about 120 kJ/mol. Additionally, a flow-through reactor was constructed
      based on the batch kinetic measurements, and a nearly complete degradation of
      ClO4- was observed under continuous-flow mode. Because the FeCl3-HCl solution has
      been successfully used in regenerating selective anion-exchange resins sorbed
      with ClO4- during water treatment, this new methodology offers a cost-effective
      means to degrade ClO4- while not altering the chemical properties of the FeCl3
      HCl regenerant solution so it can be reused, eliminating the production of
      secondary wastes.

PMID- 12785540
TI  - Photocatalytic activity, antibacterial effect, and photoinduced hydrophilicity of
      TiO2 films coated on a stainless steel substrate.
AB  - Transparent TiO2 films on stainless steel prepared by dip coating in a nonionic
      microemulsions solution have been shown to have much higher photocatalytic
      activity than those coatings on glass. Fe3+ and Fe2+ ions, diffusing from
      stainless steel substrate into TiO2 films during high-temperature calcination,
      behave as dopants to significantly affect the films' photocatalytic activity. An
      optimum calcination condition, under which the amount of diffused Fe3+ and the
      ratio of Fe3+ to Fe2+ ions favor the film's photocatalytic reaction, was
      obtained. In addition, this TiO2 films also exhibits excellent photoinduced
      hydrophilicity and antibacterial effect for the sterilization of Bacillus
      pumilus. As stainless steel is a very common material, practical systems for
      pollution treatment and disinfection may be designed based on this enhanced
      coating.

PMID- 12785541
TI  - Performance evaluation of a permeable reactive barrier using reaction products as
      tracers.
AB  - A method incorporating laboratory analysis of constituents that formed as
      reaction products was developed and used to determine the flux of groundwater
      through a zerovalent iron-based permeable reactive barrier (PRB) installed to
      treat U-contaminated groundwater. Concentrations of three nonvolatile
      constituents (Ca, U, and V) that formed as reaction products in the PRB were
      analyzed in 279 samples. Areal distributions of the reaction products indicate
      that groundwater flowed through all portions of the PRB and that nearly the
      entire volume of reactive material is treating the groundwater. Almost 9 t of
      calcium carbonate precipitated in the PRB during the first 2.7 yr of operation,
      but only 24 kg of combined U- and V-bearing minerals precipitated during the same
      period. Concentration gradients of Ca, U, and V dissolved in the groundwater
      indicate that a hydraulically upgradient portion of the PRB lost some reactivity
      during the first 2.7 yr of operation. Calculations that partially couple porosity
      changes to ZVI reactivity suggest that loss of reactivity may be more limiting
      than porosity reduction for long-term performance of the PRB. Calculations using
      groundwater concentration gradients and solid-phase concentrations indicate that
      the mean groundwater flux ranged from 11 to 24 L/min, considerably less than the
      design flux of 185 L/min. Flux values calculated with all three constituents were
      in good agreement. This method provides a more accurate determination of
      groundwater flux than is possible with flow sensor measurements, dissolved
      tracers, or Darcy's law computations.

PMID- 12785542
TI  - The hydrogen peroxide-assisted photocatalytic degradation of alachlor in TiO2
      suspensions.
AB  - Photocatalytic degradations of alachlor in TiO2 suspensions with and without the
      use of hydrogen peroxide were studied using two different monochromatic UV
      irradiations (300 and 350 nm). Direct photolysis of alachlor was a rather slow
      process, but the addition of TiO2 enhanced the reaction rates by 12 and 26 times
      using 300 and 350 nm UV irradiation, respectively. The results showed that a low
      H2O2 dosage in photocatalysis using 300 nm UV would enhance the rates by 3.3
      times, but an overdose of H2O2 will retard the rate due to the hydroxyl radicals
      are consumed. However, this process is impracticable at 350 nm due to the
      absorption characteristic of H2O2. A neutral initial pH level was found to favor
      the H2O2 assisted photocatalysis at 300 nm UV illumination. Eleven major
      intermediates were identified by liquid chromatography-electrospray ionization
      mass spectrometry (LC-ESI-MS) and MS/MS. The major degradation mechanisms of H2O2
      assisted alachlor photocatalysis include dechlorination, dealkylation,
      hydroxylation, cyclization, scission of C-O bond, and N-dealkylation. Bell-shaped
      evolution profiles of different intermediates were observed. Degradation pathways
      were proposed accordingly to illustrate series of degradation steps. The TOC
      analysis revealed the different stages of the reaction.

PMID- 12785543
TI  - Mechanistic basis for particle detachment from granular media.
AB  - Colloids may become detached from surfaces in environmental systems as a result
      of chemical and physical conditions. Many researchers reporting on colloidal
      detachment in natural and model systems have stopped short of mechanistically and
      quantitatively describing their observations. In this work, a mathematical
      construct is presented that quantitatively determines the effect of
      thermodynamics and hydrodynamics on particle detachment from surfaces in granular
      media. Using the Buckingham pi theorem, a mathematical model is structured based
      on governing dimensionless groupings. Determining dimensionless numbers
      elucidates conditions conducive for detachment in engineered and natural porous
      media. Published detachment data are compared to the mathematical model developed
      herein and provide support for its utility. Extensions of this technique have
      utility in many applications where fluid interaction with particulate-laden
      porous media is encountered.

PMID- 12785544
TI  - Health care complaining--not just another tax.

PMID- 12785545
TI  - The interrelationship of organizational characteristics of magnet hospitals,
      nursing leadership, and nursing job satisfaction.
AB  - This study examined whether magnet hospitals continue to provide higher levels of
      job satisfaction and empowerment among nurses when compared with non-magnet
      hospitals. Also studied at both types of hospitals was whether job satisfaction
      discrepancy was interlinked with leadership effectiveness and support of
      professional nursing practice. Nurses employed at magnet hospitals experienced
      higher levels of empowerment and job satisfaction due to greater access to work
      empowerment structures. The elements accounting for differences in empowerment
      and job satisfaction scores included: (1) greater accessibility of magnet nurse
      leaders, (2) better support of clinical nurse autonomous decision making by
      magnet nurse leaders, and (3) greater access to work empowerment structures such
      as opportunity, information, and resources at magnet hospitals.

PMID- 12785546
TI  - Hospital restructuring, workload, and nursing staff satisfaction and work
      experiences.
AB  - This study examined changes in patient-nurse ratios resulting from hospital
      restructuring and the relationship of such changes to nursing staff satisfaction,
      psychological health, and perceptions of hospital functioning. Data were obtained
      from 744 hospital-based nursing survivors using questionnaires. Fifty-three
      percent of staff nurses indicated an increased patient-nurse ratio. Nursing staff
      indicating increased ratios generally reported less job satisfaction, poorer
      psychological (but not physical) health, and less effective hospital functioning.

PMID- 12785547
TI  - Decertification elections in health care: some recent evidence.
AB  - This article examines union decertification elections conducted by the National
      Labor Relations Board between January 1999 and February 2002 in hospitals and
      nursing and residential care facilities. Employees petitioned 92% of all
      decertification elections. Service Employees International Union was involved in
      nearly 43% of all decertification elections and won 57%. Forty-three percent of
      all decertification elections involved bargaining units with 50 employees or
      less. Unions lost 66% of decertification elections in departments, but won 75% in
      bargaining units consisting of both professional and clerical employees. The
      union win rate in non-right-to-work states was 52% compared with 37% in right-to
      work states.

PMID- 12785548
TI  - The movement for diversity in health care management.
AB  - Efforts of health care management leaders to increase the diversity of its ranks
      have had limited success. A combination of factors, including emphasis on simply
      focusing on numeric goals and compliance with existing regulatory requirements,
      has given rise to the loss of an ethical and moral basis for why diversity should
      be embraced as a concept. The article suggests that a movement for diversity
      needs to be embraced at all levels of management and those impacting the
      healthcare management workforce, including academia and public policy makers.

PMID- 12785549
TI  - Length of stay at an all-time low.
AB  - Most health care professionals agree that the decreasing length of stay in
      hospitals is detrimental to the quality of care given to the patient. The growing
      trend over the past decade is to discharge the patient as quickly as possible.
      The decreasing length of stay has spurred many questions and controversies in
      both public and medical domains. It has brought about changes in service delivery
      and technology. Still, the question remains: Does shortened length of stay
      decrease the quality of care given? Understanding the factors of change and their
      effect on the medical environment is beneficial to all health care professionals.

PMID- 12785551
TI  - Clinical supervision: a working model for substance abuse acute care settings.
AB  - Clinical supervision is a general practice with multiple implications for health
      care settings. Applying clinical supervision is often determined by various
      organizational elements. David Powell offers a working model called the blended
      model. This article outlines the blended model and discusses its utilization in
      substance abuse acute care settings (SAACS). Furthermore, the dynamics of the
      model are dissected and identified, stressing its application. These dynamics
      include contextual variables, descriptive dimensions, organizational treatment
      philosophies, and leadership.

PMID- 12785550
TI  - Ideal and perceived satisfaction of patient care providers.
AB  - This study compared the ideal job satisfaction and perceived job satisfaction
      levels of patient care providers from labor and delivery, coronary intensive
      care, pediatric outpatient, and perioperative areas. Of the 243 surveys
      distributed, 112 (46%) patient care providers responded. The respondents included
      registered nurses, licensed practical nurses, patient care assistants, and a
      scrub technician. A dependent t test revealed a statistically significant
      difference in the providers' ideal job satisfaction and perceived job
      satisfaction (t = 16.66, df = 87, p = < .001). The mean ideal satisfaction as
      compared to the mean perceived satisfaction was 88.70 to 65.65.

PMID- 12785552
TI  - Sexuality, sexual harassment, and sexual humor: guidelines for the workplace in
      health care.
AB  - Sexual humor is common in the health care workplace. However, it may be used
      inappropriately and present a challenge to the manager. Managers must set
      appropriate standards for workplace humor. When sexual humor is not effectively
      handled, legal action may result, which wastes time and money for all involved
      and damages interpersonal relationships.

PMID- 12785553
TI  - A study of the skills and roles of senior-level health care managers.
AB  - This study identifies the most essential skills and roles of senior-level health
      care managers. The study first reviews the literature to describe major forces in
      the healthcare environment that impact management and then discusses the skills
      and roles of managers. From this, a descriptive list of skills and roles is
      created. Ten senior-level managers were interviewed to reveal six roles and
      associated skills necessary for managing in the current health care environment.

PMID- 12785554
TI  - Relocating rheumatology patients to a new infusion center at Duke: a case study.
AB  - This case study concerns relocating rheumatology patients at Duke University
      Medical Center to a new infusion center located in a physician based treatment
      setting. The case study follows the managerial decision-making process as it
      describes how the infusion center treatment site was chosen, how it was set up,
      how it functions, and what benefits to patient care it provides. A successful
      site-of-car relocation requires strong managers who are able to weigh objectively
      alternative courses of action. Moreover, the project champion must be able to
      distinguish key factors inside and outside the organization and chart the
      project's course accordingly.

PMID- 12785555
TI  - Document security: a funny thing happened on the way to the shredder.
AB  - In these days of close attention to security of information handled
      electronically, there is a tendency to overlook the security of hard-copy
      documents, particularly patient records and employee documentation. Document
      security is related to growing concerns for individual privacy; guidelines are
      furnished for protecting employee privacy by separating retention practices for
      business information from personal information. Sensitive documentation requires
      rules and procedures for processing, retaining, accessing, storing and eventually
      destroying. Also, documents that are missing or incomplete sometimes present
      unique problems for the organization. The article provides simple rules for
      safeguarding employee and patient documentation.

PMID- 12785556
TI  - A manager asks: addressing second-hand complaints.

PMID- 12785557
TI  - Use of information technology to improve the quality of health care in the United
      States.

PMID- 12785558
TI  - Quality improvement: getting to how.

PMID- 12785560
TI  - Selection incentives in a performance-based contracting system.
AB  - OBJECTIVE: To investigate whether a performance-based contracting (PBC) system
      provides incentives for nonprofit providers of substance abuse treatment to
      select less severe clients into treatment. DATA SOURCES: The Maine Addiction
      Treatment System (MATS) standardized admission and discharge data provided by the
      Maine Office of Substance Abuse (OSA) for fiscal years 1991-1995, provides
      demographic, substance abuse, and social functional information on clients of
      programs receiving public funding. STUDY DESIGN: We focused on OSA clients (i.e.,
      those patients whose treatment cost was covered by the funding from OSA) and
      Medicaid clients in outpatient programs. Clients were identified as being "most
      severe" or not. We compared the likelihood for OSA clients to be "most severe"
      before PBC and after PBC using Medicaid clients as the control. Multivariate
      regression analysis was employed to predict the marginal effect of PBC on the
      probability of OSA clients being most severe after controlling for other factors.
      PRINCIPAL FINDINGS: The percentage of OSA outpatient clients classified as most
      severe users dropped by 7 percent (p < = 0.001) after the innovation of
      performance-based contracting compared to the increase of 2 percent for Medicaid
      clients. The regression results also showed that PBC had a significantly negative
      marginal effect on the probability of OSA clients being most severe. CONCLUSIONS:
      Performance-based contracting gave providers of substance abuse treatment
      financial incentives to treat less severe OSA clients in order to improve their
      performance outcomes. Fewer OSA clients with the greatest severity were treated
      in outpatient programs with the implementation of PBC. These results suggest that
      regulators, or payers, should evaluate programs comprehensively taking this type
      of selection behavior into consideration.

PMID- 12785559
TI  - Market reform in New Jersey and the effect on mortality from acute myocardial
      infarction.
AB  - OBJECTIVE: To determine whether mortality rates for patients with acute
      myocardial infarction (AMI) changed in New Jersey after implementation of the
      Health Care Reform Act, which reduced subsidies for hospital care for the
      uninsured and changed hospital payment to price competition from a rate-setting
      system based on hospital cost. DATA SOURCES/STUDY SETTING: Patient discharge data
      from hospitals in New Jersey and New York from 1990 through 1996 and the
      Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS).
      STUDY DESIGN: A comparison between states over time of unadjusted and risk
      adjusted mortality and cardiac procedure rates. DATA COLLECTION: Discharge data
      were obtained for 286,640 patients with the primary diagnosis of AMI admitted to
      hospitals in New Jersey or New York from 1990 through 1996. Records of 364,273
      NIS patients were used to corroborate time trends. PRINCIPAL FINDINGS: There were
      no significant differences in AMI mortality among insured patients in New Jersey
      relative to New York or the NIS. However, there was a relative increase in
      mortality of 41 to 57 percent among uninsured New Jersey patients post-reform,
      and their rates of expensive cardiac procedures decreased concomitantly.
      CONCLUSIONS: The introduction of hospital price competition and reductions in
      subsidies for hospital care of the uninsured were associated with an increased
      mortality rate among uninsured New Jersey AMI patients. A relative decrease in
      the use of cardiac procedures in New Jersey may partly explain this finding.
      Additional studies should be done to identify whether other market reforms have
      been associated with changes in the quality of care.

PMID- 12785561
TI  - Medicare breast surgery fees and treatment received by older women with localized
      breast cancer.
AB  - OBJECTIVE: To determine whether area-level Medicare physician fees for mastectomy
      and breast conserving surgery were associated with treatment received by Medicare
      beneficiaries with localized breast cancer and to compare these results with an
      earlier analysis conducted using small areas (three-digit zip codes) as the unit
      of observation. DATA SOURCE: Medicare claims and physician survey data for a
      national sample of elderly (aged 67 or older) Medicare beneficiaries with
      localized breast cancer treated in 1994 (unweighted n = 1,787). STUDY DESIGN:
      Multinomial logistic regression analysis was used to estimate a model of
      treatment received as a function of Medicare fees, controlling for other area
      economic factors, patient demographic and clinical characteristics, physician
      experience, and region. PRINCIPAL FINDINGS: In 1994, average Medicare fees
      (adjusted for the effects of modifiers and procedure mix) for mastectomy (MST)
      and breast conserving surgery (BCS) were 904 dollars and 305 dollars,
      respectively. Holding other fees and factors fixed, a 10 percent increase in the
      BCS fee increased the odds of breast conserving surgery with radiation therapy
      relative to mastectomy to 1.34 (p = 0.02), while a 10 percent decrease in the MST
      fee increased the odds of breast conserving surgery with radiation therapy to
      1.86 (p < 0.01). CONCLUSIONS: Among older women with localized breast cancer,
      financial incentives appear to influence the use of mastectomy and breast
      conserving surgery with radiation therapy. This finding is consistent with the
      hypothesis that physicians are responsive to financial incentives when the
      alternative procedures have clinically equivalent outcomes and the patient's
      clinical condition does not dominate the treatment choice. We also find that the
      fee effects derived from this analysis of individual data with more precise
      measurement of both diagnosis and treatment are qualitatively similar to the
      results of the small-area analysis. This suggests that the earlier study was not
      severely affected by ecological bias or other data limitations inherent in
      Medicare claims data.

PMID- 12785562
TI  - Effects of Medicaid managed care programs on health services access and use.
AB  - OBJECTIVE: To estimate the effects of Medicaid managed care (MMC) programs on
      Medicaid enrollees' access to and use of health care services at the national
      level. DATA SOURCES/STUDY SETTING: 1991-1995 National Health Interview Surveys
      (NHIS) and a 1998 Urban Institute survey on state Medicaid managed care programs.
      STUDY DESIGN: Using multivariate regression models, we estimated the effect of
      living in a county with an MMC program on several access and use measures for
      nonelderly women who receive Medicaid through AFDC and child Medicaid recipients.
      We focus on mandatory programs and estimate separate effects for primary care
      case management (PCCM) programs, health maintenance organization (HMO) programs,
      and mixed PCCM/HMO programs, relative to fee-for-service (FFS) Medicaid. We
      control for individual and county characteristics, and state and year effects.
      DATA COLLECTION/EXTRACTION METHOD: This study uses pooled individual-level data
      from up to five years of the NHIS (1991-1995), linked to information on Medicaid
      managed care characteristics at the county level from the 1998 MMC survey.
      PRINCIPAL FINDINGS: We find virtually no effects of mandatory PCCM programs. For
      women, mandatory HMO programs reduce some types of non-emergency room (ER) use,
      and increase reported unmet need for medical care. The PCCM/HMO programs increase
      access, but had no effects on use. For children, mandatory HMO programs reduce ER
      visits, and increase the use of specialists. The PCCM/HMO programs reduce ER
      visits, while increasing other types of use and access. CONCLUSIONS: Mandatory
      PCCM/HMO programs improved access and utilization relative to traditional FFS
      Medicaid, primarily for children. Mandatory HMO programs caused some access
      problems for women.

PMID- 12785563
TI  - Chronic disease medication use in managed care and indemnity insurance plans.
AB  - OBJECTIVE: To evaluate the impact of managed care on the use of chronic disease
      medications. DATA SOURCE: Claims data from 1997 from two indemnity and three
      independent practice association (IPA) model managed care insurance plans.
      RESEARCH DESIGN: Cross-sectional analysis of claims data. DATA COLLECTION: Adult
      patients with diabetes mellitus (DM, n = 26,444), congestive heart failure (CHF,
      n = 7,978), and asthma (n = 9,850) were identified by ICD-9 codes. Chronic
      disease medication use was defined through pharmacy claims for patients receiving
      one or more prescriptions for drugs used in treating these conditions. Using
      multiple logistic regression we adjusted for patient case mix and the number of
      primary care visits. PRINCIPAL FINDINGS: With few exceptions, managed care
      patients were more likely to use chronic disease medications than indemnity
      patients. In DM, managed care patients were more likely to use sulfonylureas (43
      percent versus 39 percent for indemnity), metformin (26 percent versus 18
      percent), and troglitazone (8.8 percent versus 6.4 percent), but not insulin. For
      CHF patients, managed care patients were more likely to use loop diuretics (45
      percent versus 41 percent), ACE inhibitors or angiotensin receptor blockers (50
      percent versus 41 percent), and beta-blockers (23 percent versus 16 percent), but
      we found no differences in digoxin use. In asthma, managed care patients were
      more likely to use inhaled corticosteroids (34 percent versus 30 percent),
      systemic corticosteroids (18 percent versus 16 percent), short-acting beta
      agonists (42 percent versus 33 percent), long-acting beta-agonists (9.9 percent
      versus 8.6 percent), and leukotriene modifiers (5.4 percent versus 4.1 percent),
      but not cromolyn or methylxanthines. Statistically significant differences
      remained after multivariate analysis that controlled for age, gender, and
      severity. CONCLUSIONS: Chronic disease patients in these managed care plans are
      more likely to receive both inexpensive and expensive medications. Exceptions
      included older medications partly supplanted by newer therapies. Differences may
      be explained by the fact that patients in indemnity plans face higher out-of
      pocket costs and managed care plans promote more aggressive medication use. The
      relatively low likelihood of condition-specific medications in both plan types is
      a matter of concern, however.

PMID- 12785564
TI  - Improving care for minorities: can quality improvement interventions improve care
      and outcomes for depressed minorities? Results of a randomized, controlled trial.
AB  - OBJECTIVE: Ethnic minority patients often receive poorer quality care and have
      worse outcomes than white patients, yet practice-based approaches to reduce such
      disparities have not been identified. We determined whether practice-initiated
      quality improvement (QI) interventions for depressed primary care patients
      improve care across ethnic groups and reduce outcome disparities. STUDY SETTING:
      The sample consists of 46 primary care practices in 6 U.S. managed care
      organizations; 181 clinicians; 398 Latinos, 93 African Americans, and 778 white
      patients with probable depressive disorder. STUDY DEIGN: Matched practices were
      randomized to usual care or one of two QI programs that trained local experts to
      educate clinicians; nurses to educate, assess, and follow-up with patients; and
      psychotherapists to conduct Cognitive Behavioral Therapy. Patients and physicians
      selected treatments. Interventions featured modest accommodations for minority
      patients (e.g., translations, cultural training for clinicians). DATA EXTRACTION
      METHODS: Multilevel logistic regression analyses assessed intervention effects
      within and among ethnic groups. PRINCIPAL FINDINGS: At baseline, all ethnic
      groups Latino, African American, white) had low to moderate rates of appropriate
      care and the interventions significantly improved appropriate care at six months
      (by 8-20 percentage points) within each ethnic group, with no significant
      difference in response by ethnic group. The interventions significantly decreased
      the likelihood that Latinos and African Americans would report probable
      depression at months 6 and 12; the white intervention sample did not differ from
      controls in reported probable depression at either follow-up. While the
      intervention significantly improved the rate of employment for whites and not for
      minorities, precision was low for comparing intervention response on this
      outcome. It is important to note that minorities remained less likely to have
      appropriate care and more likely to be depressed than white patients.
      CONCLUSIONS: Implementation of quality improvement interventions that have modest
      accommodations for minority patients can improve quality of care for whites and
      underserved minorities alike, while minorities may be especially likely to
      benefit clinically. Further research needs to clarify whether employment benefits
      are limited to whites and if so, whether this represents a difference in
      opportunities. Quality improvement programs appear to improve quality of care
      without increasing disparities, and may offer an approach to reduce health
      disparities.

PMID- 12785565
TI  - Does satisfaction reflect the technical quality of mental health care?
AB  - OBJECTIVE: To analyze the relationship between satisfaction and technical quality
      of care for common mental disorders. DATA SOURCE: A nationally representative
      telephone survey of 9,585 individuals conducted in 1997-1998. STUDY DESIGN: Using
      multinomial logistic regression techniques we investigated the association
      between a five-level measure of satisfaction with the mental health care
      available for personal or emotional problems and two quality indicators. The
      first measure, appropriate technical quality, was defined as use of either
      appropriate counseling or psychotropic medications during the prior year for a
      probable depressive or anxiety disorder. The second, active treatment, indicated
      whether the respondent had received treatment for a psychiatric disorder in the
      past year. Covariates included measures of physical and mental health and
      sociodemographic indicators. PRINCIPAL FINDINGS: Appropriate technical quality of
      care was significantly associated with higher levels of satisfaction. The
      strength of the association was moderate. CONCLUSIONS: Satisfaction is associated
      with technical quality of care. However, profiling quality of care with
      satisfaction will likely require large samples and case-mix adjustment, which may
      be more difficult for plans or provider groups to implement than measuring
      technical indicators. More importantly, satisfaction is not the same as technical
      quality, and our results suggest that at this time they cannot be made to
      approach each other closely enough to eliminate either.

PMID- 12785566
TI  - Patterns and correlates of contacting clergy for mental disorders in the United
      States.
AB  - OBJECTIVE: To present nationally representative data on the part played by clergy
      in providing treatment to people with mental disorders in the United States. DATA
      SOURCES: The National Comorbidity Survey (NCS), a nationally representative
      general population survey of 8,098 respondents ages 15-54. STUDY DESIGN: Cross
      sectional survey. DATA COLLECTION: A modified version of the Composite
      International Diagnostic Interview was used to assess DSM-III-R mental disorders.
      Reports were obtained on age of onset of disorders, age of first seeking
      treatment, and treatment in the 12 months before interview with each of six types
      of professionals (clergy, general medical physicians, psychiatrists, other mental
      health specialists, human services providers, and alternative treatment
      providers). PRINCIPAL FINDINGS: One-quarter of those who ever sought treatment
      for mental disorders did so from a clergy member. Although there has been a
      decline in this proportion between the 1950s (31.3 percent) and the early 1990s
      (23.5 percent), the clergy continue to be contacted by higher proportions than
      psychiatrists (16.7 percent) or general medical doctors (16.7 percent). Nearly
      one-quarter of those seeking help from clergy in a given year have the most
      seriously impairing mental disorders. The majority of these people are seen
      exclusively by the clergy, and not by a physician or mental health professional.
      CONCLUSIONS: The clergy continue to play a crucial role in the U.S. mental health
      care delivery system. However, interventions appear to be needed to ensure that
      clergy members recognize the presence and severity of disorders, deliver
      therapies of sufficient intensity and quality, and collaborate appropriately with
      health care professionals.

PMID- 12785567
TI  - Economic expansion is a major determinant of physician supply and utilization.
AB  - OBJECTIVE: To assess the relationship between levels of economic development and
      the supply and utilization of physicians. DATA SOURCES: Data were obtained from
      the American Medical Association, American Osteopathic Assocation, Organization
      for Economic Cooperation and Development (OECD), Bureau of Health Professions,
      Bureau of Labor Statistics, Bureau of Economic Analysis, Census Bureau, Health
      Care Financing Administration, and historical sources. STUDY DESIGN: Economic
      development, expressed as real per capita gross domestic product (GDP) or
      personal income, was correlated with per capita health care labor and physician
      supply within countries and states over periods of time spanning 25-70 years and
      across countries, states, and metropolitan statistical areas (MSAs) at multiple
      points in time over periods of up to 30 years. Longitudinal data were analyzed in
      four complementary ways: (1) simple univariate regressions; (2) regressions in
      which temporal trends were partialled out; (3) time series comparing percentage
      differences across segments of time; and (4) a bivariate Granger causality test.
      Cross-sectional data were assessed at multiple time points by means of univariate
      regression analyses. PRINCIPAL FINDINGS: Under each analytic scenario, physician
      supply correlated with differences in GDP or personal income. Longitudinal
      correlations were associated with temporal lags of approximately 5 years for
      health employment and 10 years for changes in physician supply. The magnitude of
      changes in per capita physician supply in the United States was equivalent to
      differences of approximately 0.75 percent for each 1.0 percent difference in GDP.
      The greatest effects of economic expansion were on the medical specialties,
      whereas the surgical and hospital-based specialties were affected to a lesser
      degree, and levels of economic expansion had little influence on family/general
      practice. CONCLUSIONS: Economic expansion has a strong, lagged relationship with
      changes in physician supply. This suggests that economic projections could serve
      as a gauge for projecting the future utilization of physician services.

PMID- 12785568
TI  - Callers' ability to understand advice received from a telephone health-line
      service: comparison of self-reported and registered data.
AB  - OBJECTIVE: To validate users' perception of nurses' recommendations to look for
      another health resource among clients seeking teleadvice. To analyze the effects
      of different users' and call characteristics on the incorrectness of the self
      report. DATA SOURCES/STUDY SETTING: This study is a secondary analysis of data
      obtained from 4,696 randomly selected participants in a survey conducted in 1997
      among users of Info-Sante CLSC, a no-charge telenursing health-line service
      (THLS) available all over the province of Quebec. STUDY DESIGN/DATA COLLECTION:
      Self-reported advice from follow-up survey phone interviews, conducted within 48
      to 120 hours after the participant's call were compared to the data consigned by
      the nurse in the computerized call record. Covariables concerned characteristics
      of callers, context of the calls, and satisfaction about the nurses'
      intervention. Association between these variables and inaccurate reports was
      identified using multinomial logistic regression analyses. PRINCIPAL FINDINGS:
      Advice to consult were recorded by the nurse in 42 percent of cases, whereas 39
      percent of callers stated they had received one. Overall disagreement between the
      two sources is 27 percent (12 percent by false positive and 15 percent by false
      negative) and kappa is 0.45. Characteristics such as living alone (adjusted OR =
      2.5), calls relating to psychological problems (OR = 2.8), perceived seriousness
      (OR = approximately 2.6), as well as others, were associated with inaccurate
      reports. CONCLUSIONS: Telephone health-line providers should be aware that many
      callers appear to interpret advice to seek additional health care differently
      than intended. Our findings suggest the need for continuing quality control
      interventions to reduce miscommunication, insure better understanding of advice
      by callers, and contribute to more effective service.

PMID- 12785569
TI  - How do patients choose physicians? Evidence from a national survey of enrollees
      in employment-related health plans.
AB  - OBJECTIVE: This study examines the process by which patients search for and
      choose physicians. DATA SOURCE: A survey to a random sample of individuals
      between the ages of 21 and 64 with employer-related health benefits, drawn from a
      nationally representative panel of households. STUDY DESIGN: Logit models are
      used to measure the effect of patient characteristics on the probability of (1)
      using alternative sources of information to support the choice of a current
      physician, (2) seriously considering another physician before choosing a current
      physician, and (3) stating a willingness to switch physicians when information
      suggests that other health plan doctors receive higher quality ratings. PRINCIPAL
      FINDINGS: Although a minority of respondents actively searches for a physician,
      there appears to be substantial variation in the degree of consumer activism
      across patient subgroups. Poor health status, higher levels of service use in the
      past year, and stronger ties to individual physicians are associated with less
      consumer activism. At the same time, greater levels of consumer activism were
      found among racial and ethnic minorities, among those who report using
      information to choose their physicians, and among those who switched physicians
      as a result of dissatisfaction some time in the past five years. Source of
      quality information (medical experts versus patient advocates) did not influence
      stated willingness to switch physicians. CONCLUSIONS: Despite predictions of the
      increasing importance of consumer choice in shaping the health care delivery
      system, the results largely confirm the image depicted in the previous literature
      of patients as passive health care consumers of physician services, and highlight
      the importance of investments in the development of decision support tools in
      consumer-driven health care systems.

PMID- 12785570
TI  - Health care costs among smokers, former smokers, and never smokers in an HMO.
AB  - OBJECTIVE: We estimate long-term health care costs of former smokers compared
      with continuing and never smokers using a retrospective cohort study of HMO
      enrollees. Previous research on health care costs associated with former smokers
      has suggested that quitters may incur greater health care costs than continuing
      smokers, therefore, getting people to quit creates more expensive health care
      consumers. We studied the trend in cost for former smokers over seven years after
      they quit to assess how the cessation experience impacts total health care cost.
      DATA SOURCES/STUDY SETTING: Group Health Cooperative (GHC), a nonprofit mixed
      model health maintenance organization in western Washington state. STUDY DESIGN:
      Retrospective cohort study using automated and primary data collected through
      telephone interviews. PRINCIPAL FINDINGS: We find that former smokers' costs are
      significantly greater (p<.05) in the year immediately following cessation
      relative to continuing smokers, but former smokers' costs fall in year two. This
      decrease maintains throughout the six-year follow-up period. Although former
      smokers cost more than continuing smokers in the year after cessation, this
      increase appears to be transient. Long-term costs for former smokers are not
      statistically different from those of continuing smokers and cumulative health
      care expenses are lower by the seventh year postquit. Our evidence suggests that
      smoking cessation does not increase long-term heath care costs. CONCLUSIONS:
      Health care costs among former smokers increase relative to continuing smokers in
      the year after cessation but fall to a level that is statistically
      indistinguishable in the second year postquit. Any net increase in costs among
      former smokers relative to continuing smokers appears compensated for within two
      years post-quit and is maintained for at least six years after cessation.

PMID- 12785571
TI  - Developing and testing a model to predict outcomes of organizational change.
AB  - OBJECTIVE: To test the effectiveness of a Bayesian model employing subjective
      probability estimates for predicting success and failure of health care
      improvement projects. DATA SOURCES: Experts' subjective assessment data for model
      development and independent retrospective data on 221 healthcare improvement
      projects in the United States, Canada, and The Netherlands collected between 1996
      and 2000 for validation. METHODS: A panel of theoretical and practical experts
      and literature in organizational change were used to identify factors predicting
      the outcome of improvement efforts. A Bayesian model was developed to estimate
      probability of successful change using subjective estimates of likelihood ratios
      and prior odds elicited from the panel of experts. A subsequent retrospective
      empirical analysis of change efforts in 198 health care organizations was
      performed to validate the model. Logistic regression and ROC analysis were used
      to evaluate the model's performance using three alternative definitions of
      success. DATA COLLECTION: For the model development, experts' subjective
      assessments were elicited using an integrative group process. For the validation
      study, a staff person intimately involved in each improvement project responded
      to a written survey asking questions about model factors and project outcomes.
      RESULTS: Logistic regression chi-square statistics and areas under the ROC curve
      demonstrated a high level of model performance in predicting success. Chi-square
      statistics were significant at the 0.001 level and areas under the ROC curve were
      greater than 0.84. CONCLUSIONS: A subjective Bayesian model was effective in
      predicting the outcome of actual improvement projects. Additional prospective
      evaluations as well as testing the impact of this model as an intervention are
      warranted.

PMID- 12785572
TI  - A thermodynamics-based estimation model for adsorption of organic compounds by
      carbonaceous materials in environmental sorbents.
AB  - A model was developed to estimate Langmuir affinities for adsorption of low
      polarity organic compounds from either water or air by carbonaceous sorbents.
      Sorption enthalpies and entropies provided the basic information for the
      description of sorption affinities in terms of the entropy of melting and either
      solubility in water or vapor pressure. For m-xylene, polycyclic aromatic
      hydrocarbons (PAHs) and chlorobenzenes on 10 different sorbents, 80% of the
      measured sorption affinities fall within a factor of four of the model estimates.
      Equations for the limiting distribution coefficients in terms of either octanol
      air (K(OA)) or octanol-water partition (K(ow)) coefficients were derived from
      regressions of calculated affinities combined with an estimated relation between
      experimental Langmuir sorption capacities and K(ow). Estimated soot-water
      distribution coefficients were within a factor of three of measured data for
      polychlorobiphenyls (PCBs) and lower molecular weight PAHs on automotive soot
      samples and captured the dependence of PCB distribution coefficients on the
      extent of ortho substitution. For higher molecular weight PAHs, sorption was
      underestimated. For soot in sediment-water distribution coefficients of PAHs and
      PCBs, estimated values captured both the trend of measured data with K(ow) and
      the dependence on sorbate planarity. Tentative application to aerosol-air
      distribution explained the observed independence of distribution coefficient
      K(OA) relations for PCBs on the extent of ortho substitution and suggested
      nonequilibrium conditions for PAHs in comparison with recent measurements.

PMID- 12785573
TI  - Degradation of nonylphenol ethoxylates in estuarine sediment under aerobic and
      anaerobic conditions.
AB  - Nonylphenol ethoxylate (NPEO) surfactants and their metabolites are ubiquitous
      contaminants of the aquatic environment. Despite considerable interest in the
      environmental fate of these compounds due to concerns over toxicity and
      estrogenic activity, the pathways of NPEO degradation in sediments have not
      previously been reported, in spite of the fact that sediment appears to be an
      important sink for these compounds in the environment. In the present work, we
      have examined the rates and pathways of NPEO degradation in batch sediment slurry
      experiments using radiolabeled NPEO mixtures. Results suggest that NPEOs are more
      persistent in sediments under anaerobic conditions than in the presence of
      oxygen. In addition, it was illustrated that NPEO degradation proceeds via
      separate pathways in oxic and anoxic sediment. Discernible metabolites were
      identified and an overall mass balance for NPEO degradation in oxic and anoxic
      sediment was achieved. In contrast with previous studies, no evidence was
      observed for net production of nonylphenol from NPEOs during aerobic or anaerobic
      degradation. The observed relative rates at which NPEO ethoxymers disappeared in
      the sediment slurry experiments were consistent with previous reports for these
      compounds in sediment and other environmental media, although the absolute rates
      measured were somewhat faster than those reported for field sediments.

PMID- 12785574
TI  - Occurrence of several arsenic compounds in the liver of birds, cetaceans,
      pinnipeds, and sea turtles.
AB  - Concentrations of total arsenic and individual arsenic compounds were determined
      in livers of birds, cetaceans, pinnipeds, and sea turtles by using hydride
      generation-atomic absorption spectrometry and high-performance liquid
      chromatography/inductively coupled plasma-mass spectrometry. Hepatic arsenic
      concentrations in loggerhead turtles (11.2 +/- 3.0 microg/g dry wt) and black
      footed albatrosses (12.2 +/- 10.8 microg/g dry wt) were extremely high among the
      species examined, and the values were comparable with those of lower trophic
      marine animals such as fishes, cephalopods, crustaceans, and shellfishes. In all
      the species, arsenobetaine was the predominant arsenic compound in the livers.
      Especially, for black-footed albatrosses and black-tailed gull, the mean
      percentage of arsenobetaine was as high as 97.1 and 87.5, respectively, of
      extractable arsenic. The present study is among the first on arsenic speciation
      in avian species. Total arsenic concentration was strongly correlated with the
      concentration of arsenobetaine, while no significant relationship was observed
      between total arsenic concentration and other arsenic compounds in these animals.
      Because arsenobetaine is known to be rapidly excreted into the urine in humans
      and experimental animals, the observed results suggest that higher trophic marine
      animals might have a unique metabolism of arsenobetaine and that arsenobetaine
      plays an important role in the accumulation of arsenic in these animals.

PMID- 12785575
TI  - Influence of desorption and contact time on sediment-water distribution of spiked
      polychlorinated biphenyls and polycyclic aromatic hydrocarbons: relation with in
      situ distribution.
AB  - The long-term sediment-water distribution of polychlorinated biphenyls (PCBs) and
      polycyclic aromatic hydrocarbons (PAHs), spiked to Lake Ketelmeer (The
      Netherlands) sediment, was studied using a gas-purge technique. Contact times
      varied from 2 to 1,461 d for the PCBs and from 5 to 100 d for the PAHs. Purge
      induced desorption experiments lasted 300 to > 4,000 h. The initial distribution
      coefficients that were observed during the first part of the experiment were
      close to literature values for distribution after short contact times. The
      distribution coefficients increased during the purge-induced desorption
      experiments. The final distribution coefficients that were observed during the
      last part of the experiment were one to two orders of magnitude higher than the
      initial values and were close to distribution coefficients reported earlier for
      in situ PCBs and PAHs present in a field-contaminated sediment for years to
      decades. The change in distribution coefficients during a gas-purge experiment
      may resemble the long-term change in a field sediment. Final distribution
      coefficients seem to be a more relevant measure for the distribution coefficients
      of hydrophobic organic chemicals in aged field sediments than values obtained
      after short contact times.

PMID- 12785576
TI  - Reductive dechlorination of polychlorinated biphenyls in sediment from the Twelve
      Mile Creek arm of Lake Hartwell, South Carolina, USA.
AB  - Lake Hartwell is a U.S. Army Corps of Engineers reservoir system located on the
      state line between South Carolina and Georgia, USA. The lake was contaminated
      with an estimated 200 metric tons of polychlorinated biphenyls ([PCBs]; mainly
      Aroclor 1016 and 1254), and the entire Twelve Mile Creek watershed and the Seneca
      River arm of Lake Hartwell were placed on the National Priorities List. Monitored
      natural attenuation was chosen as a remedy for the contaminated sediment. The
      relatively warm temperature of Lake Hartwell and lack of significant
      cocontaminants along with the PCBs distinguish this site from others that have
      been studied for microbially mediated reductive dechlorination. Microcosm studies
      were conducted with sediment from two locations in the Twelve Mile Creek arm and
      confirmed the presence of indigenous microorganisms capable of reductively
      dechlorinating Aroclor 1254, which contains predominantly tetra-, penta-, and
      hexachlorobiphenyl. The average number of total chlorines per biphenyl decreased
      from 4.8 to 4.9 to 2.9 to 3.0, following 250 to 260 d of incubation. The maximum
      observed dechlorination rates were 0.29 to 0.87 microg-atoms Cl- per gram
      sediment dry weight per week. The onset of dechlorination activity correlated
      strongly with maximum methanogenesis, which occurred without a lag in samples
      from the site that showed signs of in situ fermentation activity. Dechlorination
      occurred primarily at the meta and para positions (58-63% removal), with no
      apparent decrease in ortho chlorines. This most closely resembles pattern M,
      characterized by preferential removal of unflanked and flanked meta chlorines.
      The microcosm results are consistent with sediment cores analyzed from the same
      locations, which indicate accumulation with depth of the same ortho- and para
      substituted congeners. It therefore appears that the success of monitored natural
      attenuation for Lake Hartwell will hinge on covering the recalcitrant PCBs with a
      sufficient amount of uncontaminated sediment to isolate them from the food chain.

PMID- 12785577
TI  - Sorption of linear alkylbenzene sulfonate to soil components and effects on
      microbial iron reduction.
AB  - When sewage sludge is applied to arable land, linear alkylbenzene sulfonate (LAS)
      is released into the environment. In soils, LAS has been shown to impede
      microbial processes, such as bacterial iron reduction. The aim of the present
      study was to quantify LAS adsorption and desorption to agricultural soils and
      iron oxides and relate this to the inhibition of microbial iron reduction. Two
      agricultural soils were used, namely, Askov (coarse sandy loam soil) and
      Lundgaard (coarse sandy soil). In both soils, LAS inhibited microbial iron
      reduction even at low LAS concentrations with 10% effect concentrations of 6 to 7
      and 26 to 32 mg LAS/kg dry-weight soil for Lundgaard and Askov soil,
      respectively. The sorption isotherms showed that sorption of LAS to iron oxides
      was 10 to 100 times stronger than sorption to the agricultural soils. Also, it
      appeared that at low LAS concentrations (< 10 mg/kg dry-wt soil), Lundgaard soil
      adsorbed approximately 10 times more LAS than Askov soil. Thus, the inhibitory
      effect of LAS on microbial iron reduction was highest in the Lundgaard soil,
      which exhibited both the strongest sorption and the lowest desorption of the two
      soils. A possible hypothesis to explain this correlation was that LAS toxicity
      toward bacterial iron reduction was, at least partly, caused by LAS adsorbed to
      iron oxides, which could interfere with transfer of electrons between the
      bacteria and their respiratory electron acceptor.

PMID- 12785578
TI  - Air-water gas exchange of toxaphene in Lake Superior.
AB  - Parallel air and water samples were collected in Lake Superior during August 1996
      and May 1997, to determine the levels and air-water exchange direction of
      toxaphene. Concentration of toxaphene in water did not vary across Lake Superior
      or between seasons (averaging 918 +/- 218 pg/L) but atmospheric levels were lower
      in May (12 +/- 4.6 pg/m3) than in August (28 +/- 10 pg/m3). Two recalcitrant
      congeners, Parlar 26 and 50, also were determined. These congeners were enriched
      in the air samples, compared to a standard of technical toxaphene, but not in the
      water. Water-air fugacity ratios varied from 1.4 to 2.6 in August and 1.3 to 4.7
      in May, implying volatilization of toxaphene from the lake. Estimated net fluxes
      ranged from 5.4 to 13 and 1.8 to 6.4 nm/m2d, respectively. The temperature
      dependence of toxaphene partial pressure (P) in air was log P/Pa = -3.291/T(a) +
      1.67, where T(a) is air temperature. By using this relationship, the atmospheric
      levels of toxaphene, fugacity ratios, and net fluxes were estimated for the
      entire year. Fugacity ratios were highest in the winter and lowest in the summer;
      thus toxaphene was predicted to undergo net volatilization from the lake during
      all months. A net removal of approximately 220 kg/year by gas exchange was
      estimated.

PMID- 12785579
TI  - Incomplete degradation of polycyclic aromatic hydrocarbons in soil inoculated
      with wood-rotting fungi and their effect on the indigenous soil bacteria.
AB  - Soil artificially contaminated with fluorene, phenanthrene, pyrene, and
      benz[a]anthracene was inoculated with the wood-rotting fungi Plrurotus ostreatus
      and Antrodia vaillantii. During 12 weeks of incubation, polycyclic aromatic
      hydrocarbon (PAH) degradation and the formation of persistent degradation
      products were monitored by chemical analysis. In addition, the effect on the
      indigenous soil bacteria was studied by plate count techniques and by measuring
      the concentration of bacteria-specific phospholipid fatty acids (PLFAs). In both
      soils inoculated with fungi, the PAH degradation was enhanced compared to the
      control soil without fungi. The white-rot fungus P. ostreatus accelerated the
      degradation rate radically the first weeks, while the effect of the brown-rot
      fungus was more pronounced at later stages during the 12-week study. In a soil
      with no amendments, the final degradation result was similar to that in the soil
      with added fungi, although the degradation pattern for the individual PAHs was
      different. Furthermore, the degradation by P. ostreatus was accompanied by an
      accumulation of PAH metabolites, that is, 9-fluorenone, benz[a]anthracene-7,12
      dione, and two compounds identified as 4-hydroxy-9-fluorenone and 4-oxapyrene-5
      one, that was not seen in the other soils. The inoculation with the white-rot
      fungus also had a large negative effect on the indigenous soil bacteria. This
      could be an important drawback of using the white-rot fungus P. ostreatus in soil
      bioremediation since a sequential fungal-bacterial degradation probably is needed
      for a complete degradation of PAHs in soil. In the soil inoculated with A.
      vaillantii, on the other hand, no metabolites accumulated, and no negative
      effects were observed on the indigenous microorganisms.

PMID- 12785580
TI  - Biodegradation of plasticizers by Rhodotorula rubra.
AB  - The degradation of plasticizers by the yeast Rhodotorula rubra J-96-1 (American
      Type Culture Collection 9449) in the presence of glucose was studied. The
      plasticizers included the commonly used bis-2-ethylhexyl adipate (B(EH)A),
      dioctyl phthalate (DOP), and dioctyl terephthalate (DOTP), and the less commonly
      used dipropylene glycol dibenzoate (D(PG)DB) and diethylene glycol dibenzoate
      (D(EG)DB). The proposal had been made that the latter two plasticizers be used as
      alternatives to the first three, which have been associated with negative
      environmental impacts. The degradation of D(PG)DB or D(EG)DB led to a significant
      increase in solution toxicity, which was associated with the production of
      metabolites resulting from the incomplete breakdown of the plasticizers. The
      toxic metabolites in the D(PG)DB system were identified as isomers of dipropylene
      glycol monobenzoate. A pathway for the formation of this metabolite was proposed.
      The metabolite observed when D(EG)DB was being degraded was tentatively
      identified as diethylene glycol monobenzoate by analogy to the D(PG)DB system. In
      contrast, no metabolites were observable and toxicity did not increase in the
      media during the degradation of B(EH)A, DOP, or DOTP by R. rubra. Collectively,
      these results do not support the use of D(PG)DB and D(EG)DB as environmentally
      safe alternatives to B(EH)A, DOP, or DOTP.

PMID- 12785581
TI  - Assessing the long-range transport potential of polybrominated diphenyl ethers: a
      comparison of four multimedia models.
AB  - Data from a comprehensive literature search of environmentally relevant physical
      chemical properties for nine polybrominated diphenyl ethers (PBDE), ranging from
      a monobrominated congener to the fully brominated decabromodiphenyl ether, were
      evaluated and adjusted to achieve both internal and interhomologue consistency.
      These data were then used in four model-based long-range transport potential
      (LRTP) assessment methods. The models TaPL3-2.10, ELPOS-1.1.1, Chemrange-2, and
      Globo-POP-1.1 were found to yield comparable predictions. A comparison of the
      LRTP estimates for the PBDEs with those of benchmark chemicals (polychlorinated
      biphenyls [PCBs]) suggest that the lower-brominated congeners have a LRTP
      comparable to that of PCBs known to be subject to significant LRT, whereas the
      highly brominated congeners have a very low potential to reach remote areas. This
      is in agreement with field measurements in remote regions that indicate that the
      lighter components of commercially produced PBDE mixtures predominate. Deviations
      between Chemrange and the models based on the concept of a characteristic travel
      distance were due to differences in the assumed height of the air compartment,
      which influences the relative importance of atmospheric degradation and
      deposition processes. The three models assuming a uniform temperature of 25
      degrees C may underestimate the LRTP of the smaller congeners. Only atmospheric
      parameters had a notable influence on the LRTP estimates by TaPL3, ELPOS, and
      Chemrange. whereas the relative enrichment of chemicals in the Arctic calculated
      by Globo-POP is additionally sensitive to the parameters related to the
      interaction of temperature with air-surface exchange and degradation in surface
      compartments.

PMID- 12785582
TI  - Methyl parathion toxicity in vegetated and nonvegetated wetland mesocosms.
AB  - Methyl parathion (MeP) was introduced into constructed wetlands for the purpose
      of assessing the influence of emergent vegetation on transport and toxicity of
      the pesticide. Two vegetated (90% cover, mainly Juncus effusus) and two
      nonvegetated wetland cells (each with a water body of 50 x 5.5 x 0.2 m) were each
      dosed with 6.5 m3 of water containing active ingredient of MeP at 6.6 mg/L
      associated with suspended soil at 400 mg/L to simulate a storm runoff event.
      Acute toxicity was assessed by sampling benthic macroinvertebrates at 5, 10, 20,
      and 40 m from the inlet before and 96 h after contamination and by in situ
      exposure of Chironomus tentans (Diptera) up to 24 h after contamination. Methyl
      parathion was detected throughout the nonvegetated wetland cells (70 microg/L at
      20 m, 8 microg/L at 40 m), whereas the pesticide was not transported through the
      vegetated wetland cells (20 microg/L at 20 m, < 0.1 microg/L at 40 m). A three
      way analysis of variance using contamination (repeated measure variable),
      location, and vegetation indicated significant negative effects of contamination
      on various insect taxa, such as mayfly nymphs and caddisfly larvae. Seven out of
      the total of 15 species revealed a significant contamination x vegetation effect,
      with individuals in the vegetated wetlands being less affected. Four species
      showed a significant contamination x location effect, confirming a higher
      toxicity in the inlet area of the wetlands. A significant three-way interaction
      of contamination x vegetation x location was detected in Chironomus sp., which
      was most strongly affected at the inlet area of the nonvegetated wetland cells.
      The in situ bioassay employing C. tentans confirmed the positive effect of
      wetland vegetation on MeP toxicity. These results demonstrate the importance of
      vegetation for pesticide mitigation in constructed wetlands.

PMID- 12785583
TI  - Effect of culture water hardness on the sensitivity of Ceriodaphnia dubia to
      copper toxicity.
AB  - We examined whether the sensitivity of Ceriodaphnia dubia to copper toxicity was
      influenced by the hardness of the water in which they were reared or in which
      they were exposed. Organisms cultured in very hard water were 1.5-fold less
      sensitive to copper than those in moderately hard water. However, the hardness of
      the exposure water had a greater (2.5-fold) effect on copper median effective
      concentration (EC50s).

PMID- 12785584
TI  - Short-term exposure to 17 alpha-ethynylestradiol decreases the fertility of
      sexually maturing male rainbow trout (Oncorhynchus mykiss).
AB  - The synthetic estrogen 17 alpha-ethynylestradiol (EE2) is a commonly used oral
      contraceptive that has been increasingly detected in sewage effluents. This study
      determined whether EE2 exposure adversely affected reproduction in sexually
      maturing male rainbow trout (Oncorhynchus mykiss). We exposed male trout to
      graded water concentrations of EE2 (10, 100, and 1,000 ng/ L) for 62 d leading up
      to the time of spawning. Semen and blood plasma samples were removed from each
      fish. Semen was used to fertilize groups of eggs from one nonexposed female. As a
      measure of fertility, eggs were incubated for 28 d after fertilization to
      determine the proportion that attained the eyed stage of embryonic development.
      Additional endpoints also measured included sperm motility, spermatocrit,
      gonadosomatic and hepatosomatic indices, testis histology, and circulating plasma
      levels of the sex steroids 17 alpha, 20 beta-dihydroxyprogesterone (17,20-DHP)
      and 11-ketotestosterone (11-KT). Exposure to 1,000 ng/L of EE2 caused complete
      mortality of the treatment group by day 57. Exposure to lower EE2 water
      concentrations (10 and 100 ng/L) caused an increase in sperm density, while a
      significant reduction in testis mass was observed only in the 100-ng/L exposure
      group. Most significantly, semen harvested from fish exposed to 10 and 100 ng/L
      EE2 caused an approximately 50% reduction in the number of eggs attaining the
      eyed stage of embryonic development. Plasma levels of 17,20-DHP in exposed fish
      were roughly twice the level of the controls, while levels of 11-KT were
      significantly reduced in fish exposed to 100 ng/L EE2. These results suggest that
      sexually maturing male rainbow trout are susceptible to detrimental reproductive
      effects of short-term exposures to environmentally relevant levels of EE2.

PMID- 12785585
TI  - Life-history characteristics of Daphnia exposed to dissolved microcystin-LR and
      to the cyanobacterium Microcystis aeruginosa with and without microcystins.
AB  - In the current study, the role of microcystin(MC)-LR in inhibiting Daphnia growth
      was examined. Somatic growth, time to first reproduction, number of newborns,
      mortality, and population growth were measured in Daphnia fed mixtures of the
      cyanobacterium Microcystis aeruginosa (with and without microcystin) with a high
      quality green algal food (Scenedesmus obliquus) to avoid nutritional deficiency.
      Microcystin-LR-containing cells caused a dramatic reduction in growth and
      resulted in death of the animals, but the addition of purified toxin (microcystin
      LR) had no effect on Daphnia growth. In contrast with the nutritional inadequacy
      hypothesis, growth on a mixture of Scenedesmus and the microcystin-free food was
      significantly reduced. This observation could not be explained from morphological
      characteristics of the strains that were uni- and bicellular. Clearance rates of
      Daphnia fed mixtures of Microcystis and Scenedesmus were significantly lower than
      rates of animals fed solely Scenedesmus. The results of an additional life
      history experiment with different quantities of Scenedesmus could not reject the
      hypothesis that reduced feeding may be the causal factor in explaining reduced
      Daphnia growth on the food mixture with microcystin-free Microcystis. Thus,
      feeding inhibition should be considered in explaining the food quality of
      Microcystis and other cyanobacteria, as it could affect the total food intake and
      consequently Daphnia growth.

PMID- 12785586
TI  - Effect of dissolved organic matter of various origins and biodegradabilities on
      the bioaccumulation of polycyclic aromatic hydrocarbons in Daphnia magna.
AB  - As a preliminary study of the influence of urban organic matter on the
      bioavailability of polycyclic aromatic hydrocarbons (PAHs), the effect of
      different types of dissolved organic matter (DOM) on the bioaccumulation of
      fluoranthene, pyrene, or benzo[a]pyrene in Daphnia magna was studied. Commercial
      humic substances, DOM from the aeration basin of a wastewater treatment plant,
      and highly biodegradable DOM (algae or animal extracts) were tested. The
      bioaccumulation of benzo[a]pyrene was reduced by each DOM (up to 80% reduction
      with humic substances). Pyrene bioaccumulation was also decreased by each DOM to
      a lesser extent. Fluoranthene bioaccumulation was affected by the presence of
      humic acids only. In each experiment, the solution containing humic DOM led to
      the lowest bioaccumulation. Supposing that only dissolved PAHs were bioavailable,
      the reduction of bioaccumulation allowed a biological estimate of the partition
      coefficients of DOM and PAH, K(DOC). The estimated coefficients were positively
      related to the aromaticity of DOM and negatively related to its biodegradability.

PMID- 12785587
TI  - Toxicity of heavy metals using sperm cell and embryo toxicity bioassays with
      Paracentrotus lividus (Echinodermata: Echinoidea): comparisons with exposure
      concentrations in the Lagoon of Venice, Italy.
AB  - Sperm cell and embryo toxicity tests using the Mediterranean sea urchin
      Paracentrotus lividus Lmk were performed to assess the toxicity of As3+, Cd2+,
      Cr3+, Ni2+, Pb2+, Cu2+, Zn2+, and Hg2+. The aim of this study was to improve
      information about the comparative sensitivity of sea urchin bioassays to the
      heavy metals, which are an important cause of contamination in the ecosystem of
      the Lagoon of Venice. Considering the data in mM/L, the order of toxicity is Hg2+
      > Cu2+ > Zn2+ > As3+ > or = Cr3+ > or = Cd2+ > or = Pb2+ > or = Ni2+ for the
      sperm cell test and Hg2+ > or = Pb2+ > Cu2+ > Zn2+ > Cd2+ > Ni2+ > As3+ > or =
      Cr3+ for the embryo test. New toxicity data for metals expressed as median
      effective concentration (EC50) and no-observed-effect concentration (NOEC) are
      reported for the Mediterranean species. Accurate observations of embryotoxic
      effects at increasing metal concentrations were done, detecting some different
      behaviors in metal toxicity. Toxicity data compared with water column and pore
      water concentrations recorded in the Lagoon of Venice (Italy) demonstrate the
      potential ability of bioassays using sea urchin to detect important contaminants
      in this ecosystem.

PMID- 12785588
TI  - Arsenic speciation in the earthworms Lumbricus rubellus and Dendrodrilus rubidus.
AB  - Two species of earthworm, Lumbricus rubellus Hoffmeister and Dendrodrilus rubidus
      (Savigny) collected from an arsenic-contaminated mine spoil site and an
      uncontaminated site were investigated for total tissue arsenic concentrations and
      for arsenic compounds by liquid chromatography-mass spectrometry (LC-MS) and
      liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS).
      For L. rubellus, whole-body total tissue arsenic concentrations were 7.0 to 17.0
      mg arsenic/ kg dry weight in uncontaminated soil and 162 to 566 mg arsenic/kg dry
      weight in contaminated soil. For D. rubidus, whole-body tissue concentrations
      were 2.0 to 5.0 mg arsenic/kg dry weight and 97 to 321 mg arsenic/kg dry weight,
      respectively. Arsenobetaine was the only organic arsenic species detected in both
      species of earthworms, with the remainder of the extractable arsenic being
      arsenate and arsenite. There was an increase in the proportion of arsenic present
      as arsenobetaine in the total arsenic burden. Lumbricus rubellus and D. rubidus
      have similar life styles, both being surface living and litter feeding. Arsenic
      speciation was found to be similar in both species for both uncontaminated and
      contaminated sites, with dose-dependent formation of arsenobetaine. When L.
      rubellus and D. rabidus from contaminated sites were incubated in arsenic-free
      soils, the total tissue burden of arsenic diminished. Initially, L. rubellus from
      the tolerant populations (from the contaminated site) eliminated arsenic in the
      first 7 d of exposure before accumulating arsenic in tissues, whereas nontolerant
      populations (from the uncontaminated site) accumulated arsenic linearly. The
      tolerant and nontolerant L. rubellus eliminated tissue arsenic linearly over 21 d
      when incubated in uncontaminated soil.

PMID- 12785589
TI  - The relationships of biochemical endpoints to histopathology and population
      metrics in feral flatfish species collected near the municipal wastewater outfall
      of Orange County, California, USA.
AB  - In July 2000, 330 individuals of three flatfish species were collected from
      reference locations and nine sites surrounding the outfall of the Orange County
      (CA, USA) Sanitation District (OCSD) municipal wastewater discharge. Species
      included hornyhead turbot (Pleuronichthys verticalis), English sole (Pleuronectes
      vetulus), and bigmouth sole (Hippoglossina stomata). Livers of sampled animals
      were examined for the expression of vitellogenin (in males), cytochrome P450 1A
      (CYP1A), and DNA damage (comet assay). Biliary fluorescent aromatic compounds
      (FACs) were also measured. Comparisons with tissue and sediment contaminant
      residues, liver histopathology, and population estimates were assessed to
      determine whether relationships exist between levels of biological organization.
      The CYP1A results indicated exposure to planar aromatic hydrocarbons at one
      nearshore site. Regression analysis of all English sole CYP1A to total sediment
      polychlorinated biphenyls (PCBs) (r2 = 0.97; p < 0.05) indicated a significant
      correlation. Widespread exposure to estrogens was observed at all sites without
      correlation to the abundance of the three species examined. Fluorescent aromatic
      compounds demonstrated no correlation to CYP1A expression. Overall,
      histopathology and biochemical endpoints did not indicate significant adverse
      effects in fish at the OCSD outfall.

PMID- 12785590
TI  - Variation, replication, and power analysis of Myriophyllum spp. microcosm
      toxicity data.
AB  - Myriophyllum spp. have been proposed as a new standard laboratory aquatic
      macrophyte test species for the registration of pesticides. The main objectives
      of this investigation were to determine the power of Myriophyllum sibiricum and
      Myriophyllum spicatum toxicity data derived from an outdoor microcosm bioassay,
      to evaluate the variation of 10 different aquatic plant endpoints and to
      calculate the minimum detectable difference for these endpoints, to determine the
      replication required to detect ecologically significant changes from control for
      these endpoints, and to make recommendations for future field studies with
      Myriophyllum spp. Control data from four different studies that characterized
      haloacetic acid toxicity with Myriophyllum spp. for durations of three to six
      weeks during the summer of 1999 with five treatment levels (n = 3), including
      control, were examined. Endpoint coefficient of variation ranged, on average,
      from 6 to 28%. Node number and plant length endpoints were consistently the most
      statistically powerful for both plant species. It was possible to detect
      approximately 30% change from control in both endpoints with high statistical
      power (beta = 0.2, alpha = 0.05, n = 3). The range of minimum detectable
      differences was 40 to 60% for the other endpoints. Replication to detect a > or =
      25% change from control would require an n of 2 to 21, depending on the endpoint.
      Myriophyllum sibiricum had slightly lower coefficients of variation and thus
      required fewer replicates than M. spicatum to be statistically significantly
      different from control values. Variation within microcosm studies was not
      significantly different from that of controlled laboratory studies, implying that
      most of the variation observed in the field is inherent in the plants. Based on
      statistical sensitivity, ecological relevance, and toxicological sensitivity, we
      recommend using plant length and root endpoints as indicators of toxicity under
      field conditions.

PMID- 12785591
TI  - Pyrethroid stimulation of ion transport across frog skin.
AB  - Pyrethroids are grouped into two classes (types I and II) because of the absence
      or presence of an alpha-cyano substituent and the production of a different
      intoxication syndrome in rodents. In this study, we investigated the effect of
      pyrethroids on the ion transport across frog skin (Rana esculenta). The short
      circuit current value (estimate of ion transport) was increased by each of the
      eight pyrethroids tested, with the following order of potency: lambda-cyhalothrin
      > deltamethrin > alpha-cypermethrin = beta-cyfluthrin > bioallethrin > permethrin
      > bioresmethrin > phenothrin. The first four compounds are type II pyrethroids.
      Therefore, ion transport is stimulated more by type II pyrethroids than by type
      I. Experiments performed in the presence of amiloride support the conclusion that
      pyrethroids mainly increase Na+ absorption and to a lesser extent Cl- secretion.
      In these experiments, no systematic difference between type I and II pyrethroids
      was found. Finally, the stimulation by pyrethroids was inhibited by indomethacin
      and W7 (inhibitors of cyclooxygenases and the Ca2+/calmodulin system,
      respectively). These observations suggest that pyrethroids do not directly affect
      the epithelial Na+ channel (ENaC) but indirectly influence an intracellular event
      involved in ENaC modulation and linked to the Ca2+ signaling cascade.

PMID- 12785592
TI  - Avian food selection with application to pesticide risk assessment: are dead and
      desiccated insects a desirable food source?
AB  - Past evaluations of pesticide exposure have been conducted with substantial
      uncertainty regarding avian consumption of contaminated food items. One question
      is whether birds consume invertebrates that are killed by a chemical application
      and that may present an increasing chemical concentration as they desiccate. We
      addressed the research question in two phases. First, a laboratory study was
      conducted in which wild-caught birds were individually offered three food
      choices, i.e., live, fresh-dead, and desiccated insect larvae. Second, these same
      food choices plus live, fresh-dead, and desiccated crickets were presented in
      study plots in two agricultural crops, i.e., a cornfield and an orchard. The
      experimental food items were monitored with videography equipment to determine
      their fate and to compare laboratory and field results. Laboratory results showed
      that birds have a strong preference for live and fresh-dead prey over desiccated
      prey, with live prey taken before fresh-dead prey in most trials. The field study
      revealed a similar preference for live prey over desiccated prey, with preference
      for fresh-dead prey intermediate to the two other types.

PMID- 12785593
TI  - Copper-induced modifications of the trophic relations in riverine algal-bacterial
      biofilms.
AB  - The effects of copper (Cu) on photosynthetic riverine biofilms were studied in
      artificial stream channels. Direct effects on the composition and functioning of
      the biofilms were investigated using plant pigments, community-level
      physiological profiles (CLPP), and pulse-amplitude-modulated (PAM) fluorescence.
      Copper caused a significant reduction of microalgal biomass and induced a shift
      in the population from diatoms to cyanobacteria. However, a decrease in biomass
      indicated that the replacement of species was not totally effective to counteract
      the toxic effects of Cu. A direct effect of Cu could also be shown in the
      bacterial community, and, furthermore, changes in the CLPP could be related to
      the Cu treatment. Copper-exposed biofilms lost the capacity to use between 11 and
      15% of the substrates, but many of the remaining capacities became more robust,
      indicating an increased Cu tolerance due to the exposure. The change in the
      biofilm microbial composition points to the indirect effects of Cu on biofilms
      due to the close interdependence between biofilm autotrophic and heterotrophic
      compartments. Grazing by snails, which appeared to be an important factor
      structuring biofilms without any Cu addition, had a very minor effect on Cu
      exposed biofilms. Although grazing changed the bacterial composition, its effects
      were not detected either on the algal community or on the biofilm community
      tolerance to Cu.

PMID- 12785595
TI  - Mechanism of acute silver toxicity in Daphnia magna.
AB  - Daphnids (Daphnia magna) were exposed to AgNO3 at 0.303 +/- 0.017 microg silver/L
      (46.9% as Ag+), in the absence of food, in moderately hard synthetic water under
      static conditions for up to 48 h. Results from accumulation experiments
      demonstrated that silver body burden was inversely related to body mass. Daphnids
      exposed to silver exhibited ionoregulatory disturbance, which was characterized
      by decreases in whole-body sodium concentration. This ionoregulatory disturbance
      was explained, at least in part, by a competitive inhibition of the whole-body
      sodium uptake (six- to sevenfold increase in the Michaelis constant with no
      change in maximal velocity), which was complete by 1 h of exposure, and resulted
      in approximately 40% inhibition of sodium influx from the water. A rapidly
      developing inhibition of whole-body Na+,K(+)-dependent adenosine triphosphatase
      (Na+,K(+)-ATPase) activity, significant by 2 h and complete at 90% blockade by 12
      h, also was observed during exposure to AgNO3. Therefore, these findings clearly
      demonstrate that the key mechanism involved in acute Ag+ toxicity in D. magna,
      the most sensitive freshwater organism tested to date, resembles that described
      for freshwater fish--that is, inhibition of active sodium uptake by blockade of
      Na+,K(+)-ATPase. Furthermore, the results showed that Na+,K(+)-ATPase inhibition
      was directly related to silver accumulation in the whole body of D. magna.
      However, the nature of the sodium uptake inhibition (competitive vs
      noncompetitive in fish) and the fact that whole-body chloride concentration was
      not disturbed in daphnids was different from fish. With regard to the biotic
      ligand model (BLM) for silver, our results yielded a log K value of about 8.9.
      However, the current version of the BLM uses a rainbow trout log K value (7.3)
      but achieves the correct sensitivity of the model for daphnids by reducing the
      saturation of toxic sites needed to cause toxicity. An alternative way may be to
      use the log K value derived from the present results.

PMID- 12785594
TI  - Effects of the androgenic growth promoter 17-beta-trenbolone on fecundity and
      reproductive endocrinology of the fathead minnow.
AB  - Trenbolone acetate is a synthetic steroid that is extensively used in the United
      States as a growth promoter in beef cattle. The acetate is administered to
      livestock via slow-release implants; some is converted by the animal to 17-beta
      trenbolone, a relatively potent androgen receptor agonist in mammalian systems.
      Recent studies indicate that excreted 17-beta-trenbolone is comparatively stable
      in animal waste, suggesting the potential for exposure to aquatic animals via
      direct discharge, runoff, or both. However, little is known concerning the
      toxicity of trenbolone to fish. Our goal was to assess the effects of 17-beta
      trenbolone on reproductive endocrinology of the fathead minnow (Pimephales
      promelas). An in vitro competitive binding study with the fathead minnow androgen
      receptor demonstrated that 17-beta-trenbolone had a higher affinity for the
      receptor than that of the endogenous ligand, testosterone. Male and female fish
      were exposed for 21 d to nominal (target) concentrations of 17-beta-trenbolone
      ranging from 0.005 to 50 microg/L. Fecundity of the fish was significantly
      reduced by exposure to measured test concentrations > or = 0.027 microg/ L. The
      17-beta-trenbolone was clearly androgenic in vivo at these concentrations, as
      evidenced by the de novo production in females of dorsal (nuptial) tubercles,
      structures normally present only on the heads of mature males. Plasma steroid
      (testosterone and beta-estradiol) and vitellogenin concentrations in the females
      all were significantly reduced by exposure to 17-beta-trenbolone. The 17-beta
      trenbolone also altered reproductive physiology of male fathead minnows, albeit
      at concentrations much higher than those producing effects in females. Males
      exposed to 17-beta-trenbolone at 41 microg/L (measured) exhibited decreased
      plasma concentrations of 11-ketotestosterone and increased concentrations of beta
      estradiol and vitellogenin. Overall, our studies indicate that 17-beta-trenbolone
      is a potent androgen and reproductive toxicant in fish. Given the widespread use
      of trenbolone acetate as a growth promoter, and relative stability of its
      metabolites in animal wastes, further studies are warranted to assess potential
      ecological risk.

PMID- 12785596
TI  - Toxicity of chemicals to microalgae in river and in standard waters.
AB  - The influence of the composition of natural waters on the toxicity of chemicals
      to microalgae was studied on samples representative of western European rivers.
      Effects of zinc, pentachlorophenol (PCP), 4-nonylphenol (4-NP), phosalone, and
      2,4,5-trichloroaniline (TCA) on algal growth were tested in river waters without
      adding any nutrients or cosolvents, and in the International Standards
      Organization (ISO) medium for comparison. The mean values of effective
      concentrations reducing the algal growth by 50% (EC50s) after 72 h based on
      measured concentrations did not differ significantly in natural waters and in
      standard medium for 4-NP (0.5 mg/L) and phosalone (0.8-0.9 mg/L). These values
      were two or three times higher in rivers than in ISO medium for PCP (0.25 vs 0.1
      mg/L), TCA (1.69 vs 0.73 mg/L), and zinc (0.20 vs 0.056 mg/L). Although the mean
      values were of the same order of magnitude, the distribution of the EC50 values
      ranged over 1.5 and 2 log concentrations in surface waters. Therefore, in view of
      a refined hazard assessment of a chemical on a local scale, it would be advisable
      to use the actual river water of the concerned aquatic environment in testing.
      Correlations between toxicity data and the physicochemical characteristics of the
      waters identified classic parameters such as water hardness or conductivity as
      factors that significantly influenced the toxicity of the ionizable compounds PCP
      and zinc. On the other hand, organic materials or suspended solids, but only at
      high levels, affected the toxicity of 4-NP, an organic chemical with high
      adsorption potential. No correlation could be drawn for phosalone and TCA.

PMID- 12785597
TI  - Predicting the bioavailability of copper and zinc in soils: modeling the
      partitioning of potentially bioavailable copper and zinc from soil solid to soil
      solution.
AB  - This research produced statistically based, semimechanistic models describing
      partitioning of Cu and Zn in 40 soils from the United States, Canada, the United
      Kingdom (UK), The Netherlands, and Chile with widely varying characteristics. Two
      different types of models were constructed, partitioning models and competitive
      adsorption models. Multiple linear regression (MLR) was employed to prioritize
      over 30 different soil characteristics. Multiple linear regression yielded
      equations predicting the partitioning of Cu and Zn. Equations were also created
      that estimated the potentially bioavailable fraction of Cu and/or Zn. Data from
      plant uptake studies (which are reported separately) governed the choice of a
      suitable chemical soil extraction that estimated bioavailable Cu (0.01 M HCl) and
      bioavailable Zn (0.01 M CaCl2). Soil pH (1:1 soil:deionized water [DI H2O]) and
      percent organic matter accounted for approximately 70% of the variability in Cu
      partitioning and 80% of the variability in bioavailable Cu in the 40 soils
      studied. For Zn, soil pH alone accounted for roughly 75% of the partitioning
      variability and 80% of the variability for the estimated bioavailable portion.
      The results presented here were used in conjunction with results from the plant
      uptake studies for the creation of models to assess the potential bioavailable
      metal associated with any given soil from a wide variety of locations.

PMID- 12785598
TI  - Prediction of ecological no-effect concentrations for initial risk assessment:
      combining substance-specific data and database information.
AB  - A new method is proposed to derive predicted no-effect concentrations (PNECs) for
      initial risk assessments for aquatic ecosystems from a limited set of single
      species toxicity data. The method includes three steps. First, acute toxicity
      data are divided by an acute-to-chronic assessment factor to obtain chronic
      toxicity data. Subsequently, chronic toxicity data are averaged to obtain an
      average hazardous concentration (HC50). Finally, the HC50 is divided by an
      interspecies assessment factor to obtain a PNEC. Both assessment factors are
      derived as probability distributions from an extensive ecotoxicological database.
      The interspecies assessment factor is combined with substance-specific toxicity
      data using Bayesian statistics. The proposed method optimizes the use of the
      available ecotoxicological information and it produces an uncertainty estimate of
      the PNEC. Sample calculations indicate that the proposed method may provide a
      good alternative for currently applied methods for initial risk assessment,
      particularly if few toxicity data are available.

PMID- 12785599
TI  - Demography of short-tailed shrew populations living on polychlorinated biphenyl
      contaminated sites.
AB  - In ecological risk assessment, a key necessity is to understand how contaminants
      known to have negative impact on laboratory mammals affect the population
      demography of mammals living in their natural environment. We examined the
      demography of six local populations of the short-tailed shrew (Blarina
      brevicauda) living in eastern deciduous forest palustrine habitat along the
      Housatonic River (MA, USA) on soils contaminated with a range of polychlorinated
      biphenyl (PCB) concentrations (1.5-38.3 ppm). The objective of the study was to
      assess whether PCBs adversely affect the population demography of these small
      mammals living in their natural environment. Blarina were selected for study
      because they would be expected to readily bioaccumulate PCBs from the soil.
      Populations were intensively live trapped on 1-ha grids from spring to autumn
      2001. There was no relationship between any demographic parameter and PCB soil
      concentrations. Densities were high (usually exceeding 20/ha, and on two grids
      exceeded 60/ha in summer); survival was good (typically 60-75% per 30 d); and sex
      ratio, reproduction rates, growth rates, and body mass were within the ranges
      reported in the literature. Thus, these shrew populations showed no detectable
      impact on their population demography from living on PCB-contaminated sites.

PMID- 12785600
TI  - Complexity in multimedia mass balance models: when are simple models adequate and
      when are more complex models necessary?
AB  - Three environmental multimedia models of varying degrees of complexity are
      compared to assess when simple models are adequate and when more complex models
      are advantageous. The simplest model, the level II (L-II) model, assumes all
      environmental media are at chemical equilibrium, whereas the more complex models
      treat chemical disequilibrium between well-mixed media (standard level IV [L-IV]
      model) or the major media are subdivided into separate layers to simulate
      heterogeneity (high-resolution level IV [HR-IV] model). The three models are
      compared for their performance in predicting steady-state, regional
      concentrations; dynamic, local-scale concentrations; and chemical persistence in
      the environment. The results indicate that the L-IV model often provides adequate
      regional simulations when chemical emission occurs to air or water. This model
      also is useful for assessing chemical persistence in both steady-state and
      dynamic scenarios. More complex models, such as the HR-IV model, are suggested
      for local-scale, dynamic simulations or when the chemical emission occurs to soil
      because they better characterize rates of intramedia transport, which can greatly
      affect the model predictions. The simplest L-II model predicts environmental
      concentrations that can differ significantly from those of more complex models,
      but it is useful for establishing partitioning tendencies and for ranking
      chemicals for their relative persistence in steady-state situations.

PMID- 12785601
TI  - Financial restraint, budget cuts and outsourcing: impact of the new public
      management of health care in Victoria.

PMID- 12785602
TI  - Health issues of children in foster care.
AB  - Community health nurses provide care to children in foster care. Nurses who
      understand the health needs of the foster care population are better prepared to
      assess health status, provide appropriate services and evaluate the care. The
      health needs of these children are related to the reason for their placement in
      foster care, the lack of continuity of caregivers, and the health care systems
      available. The health issues are especially acute in the United States where the
      number of children in foster care has reached over 500,000. (Leslie et al., 2000)
      The health issues include chronic physical problems, developmental delays, and
      especially, mental health issues.

PMID- 12785603
TI  - The scope of enrolled nurse practice: a review of the literature.
AB  - In this paper the scope of nursing practice of enrolled nurses (EN) is discussed
      within the context of the current demands of the health care environment and the
      impact of a changing grade mix for qualified nurses. Discussion is provided about
      EN practice, roles, functions, and competencies. The need for consistency in
      legislative and national guidelines, educational preparation, and the
      implementation of a decision-making framework is argued.

PMID- 12785604
TI  - Emergency Department Mental Health Triage and Consultancy Service: an advanced
      practice role for mental health nurses.
AB  - This paper describes a four-month preparatory training program for mental health
      nurses to provide an Emergency Mental Health Triage and Consultancy Service in
      the emergency department. The emergency department is an important gateway for
      patients presenting with psychiatric/psychosocial problems and mental health
      professionals need to provide prompt and effective care to this group of
      patients. Prior to the implementation of the service, it was acknowledged that
      occupational stress and burnout could affect the turnover of mental health nurses
      in the department. Therefore, a training program was employed to prepare a number
      of experienced mental health nurses to work at an advanced practitioner level.
      The four-month training program developed at Fremantle Hospital in Western
      Australia provided support, guidance and clinical supervision. In the first 12
      months of the service, five mental health nurses completed the program, thus
      creating a pool of nurses who were able to provide the service. The results
      demonstrated that providing mental health nurses with a structured program was
      instrumental in facilitating their movement to an advanced practitioner level.
      The nurses were able to apply advanced knowledge and skills to assess and manage
      clients with complex mental health /psychosocial problems. Furthermore, on
      leaving the emergency department these nurses were able to utilise the advanced
      skills in other areas of mental health nursing practice.

PMID- 12785605
TI  - Baccalaureate nursing students' experiences of anxiety producing situations in
      the clinical setting.
AB  - The purpose of this study was to identify the clinical experiences of nursing
      students that were anxiety provoking and examine the relationship between the
      level of trait anxiety and the clinical experience that produced anxiety in
      nursing students. A descriptive correlational design collected data from 61
      nursing students in their last semester of the baccalaureate nursing program
      using survey questionnaires that captured demographic data and included the Trait
      Anxiety Scale and the Clinical Experience Assessment form. Analyses of data
      indicate that 36% of the students experienced a moderate level of anxiety.
      Clinical experiences related to arriving late, being observed by instructors,
      responding to initial experiences, having a fear of making mistakes, and talking
      to physicians were the most anxiety producing for these students. A significantly
      positive relationship (r = .40, p < .05) was found between the trait anxiety and
      clinical experience that was anxiety producing. A higher level of perceived
      anxiety accompanied the following clinical experiences; being observed by
      instructors (F = 3.44, p = .04), doing beforehand in-hospital preparation (F =
      4.46, p < .02), asking questions of faculty (F = 4.38, p < .02), being evaluated
      by faculty (F = 3.37, p < .04), and reporting to team leader (F = 3.60, p < .05).
      The most anxiety producing clinical experiences in nursing students before
      graduation are evaluated with descriptive data. Results would provide useful
      insights for faculty and senior nursing students involved in clinical practice,
      and have implications for education, further research, and clinical support.

PMID- 12785606
TI  - Morbidity and mortality rates in women with heart disease: lessons in gender
      differences from Korea.
AB  - Korean health statistics and available research were reviewed, focusing on the
      gender differences in morbidity and mortality rates of heart disease, and factors
      affecting health outcomes of heart disease internationally with Korea. The growth
      rate and aging of population, and the morbidity and mortality rate from heart
      disease among Koreans were compared to the data provided by the World Health
      Organization (WHO) and the United Nations (UN). Both morbidity and mortality
      rates from heart disease were higher among women than among men in Korea.
      However, most of the knowledge about heart disease was based on research
      conducted on men, and not much is known about women with heart disease. The lack
      of information about women with heart disease may contribute to delay in
      diagnosis and treatment, longer stays in the hospital, increased medical costs
      and a higher mortality rate among women than among men in Korea.

PMID- 12785607
TI  - Then suddenly he went right off the rails: mothers' stories of adolescent
      cannabis use.
AB  - Adolescent drug use provides challenges for parents, health professionals and the
      wider community. Of those adolescents who use drugs, cannabis is often the drug
      of choice. A number of adolescents will develop problems associated with cannabis
      use, and the burden of managing these problems will fall on the family,
      particularly the mother. This paper explores adolescent cannabis use from the
      perspective of mothers of affected young people. Twelve women took part in
      conversational style audio-taped interviews. Stories were extracted from the
      resulting narratives and were analysed guided by the work of Anderson and Jack
      (1991). Detailed findings are grouped under the themes: First awareness: 'I
      couldn't deny it was happening'; Constant vigilance: 'I watched his every move';
      Cannabis and family life: 'I'd start to shake when he walked into the house';
      Disrupted lives: 'I was terrified he'd go to prison'; Shifting aspirations: 'just
      staying alive'; and, Maintaining a loving relationship: 'always told him I loved
      him'. Implications for nursing practice are drawn from the findings.

PMID- 12785608
TI  - Studying women nurse academics: exposing workplace violence in Australia: Part 1.
AB  - This article is the first in a two part series on research investigating the
      lived experiences of women nurse academics in Australia. This is part of a larger
      research study involving participants from Australia, New Zealand, the United
      States of America and the United Kingdom. The aim of this research was to
      investigate the participants' professional experiences and progression within
      their respective school of nursing and university. This article focuses on the
      literature on workplace violence and research methodology. The importance of
      storytelling and the relationship between emotional safety and sensitive
      disclosures is also addressed.

PMID- 12785609
TI  - Studying women nurse academics: exposing workplace violence in Australia: Part 2.
AB  - This article is the second in a series on workplace violence in academia. The
      specific findings on women nurse academics' experiences with violence in
      Australian universities are revealed. Findings indicate that Australian
      universities are competitive with wide spread violence. Participants revealed
      they were not supported nor recognised for their workplace contributions.
      Violence predominated in schools of nursing rather than the broader university.
      It is argued these findings need public dissemination to improve workplace
      environments and eliminate violence. It is noted that the results reported are
      part of a larger research study on progression and professional development of
      women nurse academics.

PMID- 12785610
TI  - Uncovering the meaning of 'being safe' in practice.
AB  - This paper moves away from the prevalent discourse of competence to consider the
      meaning of the experience of 'being safe' within the context of childbirth. It
      offers findings from a doctoral study, informed by the philosophies of Heidegger
      and Gadamer. Following ethical approval, the data was collected in New Zealand by
      tape-recorded interviews of 5 midwives, 4 obstetricians, 1 general practitioner
      and 10 women. The method was informed by van Manen. The findings reveal that in
      seeking the meaning of being safe one needs to be aware that the unsafety may
      already be present in the situation. Practitioners may be able to do little to
      rectify the unsafeness. There is, however, a spirit of safe practice, explicated
      in this paper, that is likely to make practice as safe as it can possibly be.
      Wise practitioners are ever mindful that a situation may be or become unsafe, and
      are always aware of their own limitations.

PMID- 12785611
TI  - Re-thinking the theory-practice relationship in nursing: an alternative
      perspective.
AB  - The alleged gap between theory and practice in nursing is usually understood as
      dissonance between what is taught in educational institutions and that which is
      performed in the every day world of nursing practice. Historically strategies
      devised to enhance the relationship between theory and practice have focused upon
      manipulating factors in the environment in which learning takes place. Thus far,
      this has at best proved to be only partially successful. To increase
      understanding of the relationship this paper proposes the emerging and
      complementary theory of enactivism. Enactivism is a theory that enfolds the
      student, the context for learning and the leaned as intimate components.

PMID- 12785612
TI  - The Lighthouse Foundation.
AB  - The Lighthouse Foundation is a not-for-profit organisation, dedicated to
      empowering young people to take responsibility for their own lives. Lighthouse
      provides long-term care and support within a family style environment, to young
      people aged between 15 and 22 years, who may otherwise be homeless. There are
      currently seven homes operating in Victoria. The Lighthouse model is unique in
      meeting many of the long-term needs of disadvantaged young people. Emphasis is
      placed on relationships and community, providing young people with an environment
      where they are trusted, challenged, and can thrive intellectually, physically,
      socially, spiritually and emotionally. A sense of being, and belonging, is
      encouraged.

PMID- 12785613
TI  - Autocorrelation problems in short time series.
AB  - The work of Huitema (1985) on autocorrelation in behavioral data suggests that
      the use of conventional statistical methods is justified. The present study
      restates the problem of autocorrelation by analyzing 100 baselines of small
      samples designs published in the Journal of Applied Behavior Analysis during
      1992. The results show a negative bias in the autocorrelations, especially with
      very small samples. The autocorrelation values are normally distributed, and the
      method of Davies, Trigg, and Newbold (1977) is the most accurate in calculating
      the standard deviation.

PMID- 12785614
TI  - Development of an ethanol model using social insects: II. Effect of Antabuse on
      consumatory responses and learned behavior of the honey bee (Apis mellifera L.).
AB  - The ability of Antabuse (disulfiram) to influence ethanol consumption and
      learning in harnessed honey bees was investigated. In the first series of
      experiments a factorial design was used with 5 levels of ethanol concentration
      (0%, 1%, 5%, 10%, 20%), 4 doses of Antabuse (0, 37 microg/g, 3.7 microg/g, .37
      microg/g), and 2 testing intervals (1 min., 10 min.). Animals were fed a single 1
      microl dose of Antabuse and contact time with an ethanol solution measured. A
      second series of experiments investigated the influence of Antabuse on the
      formation of Pavlovian conditioning of the proboscis extension reflex. A
      factorial design was used with two levels of training (paired, unpaired), three
      levels of ethanol (0%, 1%, 5%), and 2 levels of pretreatment (distilled water,
      3.7 microg/g). Analysis of the consumption experiments indicate that pretreatment
      with Antabuse reduces ethanol intake, although there was substantial variability.
      The findings of the Pavlovian experiments suggest that pretreatment with Antabuse
      significantly reduced responding to a CS signaling the availability of ethanol.

PMID- 12785615
TI  - Homosexual parents in British custody appeals.
AB  - 6 British child custody appeal cases including a homosexual parent were compared
      with 6 randomly drawn appeal cases between heterosexual parents for parental and
      mental instability, partners' instability, residential instability, criminality,
      and lying, and having harmed the children and exposing children to harms. In 3 of
      the 6 cases the homosexual or his associates were recorded as engaging in
      criminality, in another 2 cases with lying. In one of the 6 homosexual cases the
      children were recorded as harmed. The 9 recorded harms or probable harms to
      children in cases involving a homosexual parent were attributed to the homosexual
      or her associates: children were recorded as harmed and exposed to the harm of
      neglect in one of the 6 comparison cases.

PMID- 12785616
TI  - Birth order effects in dominance: failure to support Sulloway's view.
AB  - Contrary to Sulloway's 1996 assertion that firstborns should score higher than
      laterborns on measures of dominance, the dominance scores for 76 firstborn
      undergraduate students (50 women, 26 men) did not differ significantly from the
      scores of 75 laterborn students (48 women, 27 men) on the 16PF dimension of
      Dominance vs Submissiveness (Factor E). Further research into possible
      differences in performance strategies between laterborns and firstborns in
      childhood vs adulthood is necessary to evaluate Sulloway's theory of ordinal
      position definitively.

PMID- 12785617
TI  - Validation of the Arabic Version of the Group Personality Projective Test among
      university students in Bahrain.
AB  - Using confirmatory factor analytic techniques on data generated from 200 students
      enrolled at the University of Bahrain, we obtained some construct validity and
      reliability data for the Arabic Version of the 1961 Group Personality Projective
      Test by Cassel and Khan. In contrast to the 5-factor model proposed for the Group
      Personality Projective Test, a 6-factor solution appeared justified for the
      Arabic Version of this test, suggesting some variance between the cultural groups
      in the United States and in Bahrain.

PMID- 12785619
TI  - Instructor's transformational leadership: university student attitudes and
      ratings.
AB  - We extend leadership research by examining the effect of an instructor's
      transformational leadership on university students. 120 undergraduate students
      provided ratings for their instructors on Charisma, Intellectual Stimulation, and
      Individual Consideration as well as the Instructors' Performance and the
      Students' Involvement in class. Multiple regression analyses indicated that
      Intellectual Stimulation and Charisma together accounted for 66.3% of the
      variance in the prediction of Instructor's Performance ratings. In turn,
      Intellectual Stimulation and Individual Consideration combined to account for
      55.1% of the variance in predicting Student Involvement.

PMID- 12785618
TI  - Buying books online: follow-up.
AB  - In a sample of 72 undergraduates, purchasing books online was predicted by their
      computer/Internet skills.

PMID- 12785620
TI  - Correlations for perceived family environmental factors with substance use among
      adolescents in South Africa.
AB  - Perceived family environmental factors were used to predict self-reported use of
      substances (drugs or alcohol) among adolescents in South Africa. 435 high school
      students (ages 15 to 19 years, M=17.2 yr., SD=1.34) answered a questionnaire
      which included questions on demographic variables, the Family Environmental
      Scale, and questions on substances used (drugs or alcohol). Logistic regression
      analysis indicated that scores on family conflict and low family moral-religious
      emphasis were significantly associated with drug use (57.9% of the variance was
      accounted for) and use of alcohol (62.3% of the variance was accounted for).
      Programmes for the reduction of substance use among adolescents should include
      activities designed to reduce family conflict and strengthen family moral
      religious emphasis.

PMID- 12785621
TI  - Relations of daily hassles with both anxious and depressed mood in students.
AB  - Stressful life experiences have been related to emotional distress, but whether
      different classes of stressful events are associated with different emotional
      reactions has not been assessed. In this study, 34 college students completed the
      Inventory of College Students' Recent Life Experiences, State-Trait Anxiety
      Inventory, and Beck Depression Inventory. Consistent with previous research, most
      classes of daily hassles were significantly related to both depression and
      anxiety. The nonsignificant difference for one class of life experience,
      Friendship Problems, to be more strongly associated with anxiety than depression
      should be studied carefully.

PMID- 12785622
TI  - Topics of marital disagreement among African-American and Euro-American
      newlyweds.
AB  - To see what issues couples most and least often reported as topics of marital
      disagreement, survey data were analyzed for 113 African-American and 131 Euro
      American couples reporting in the first and third years of marriage. Friedman
      tests showed that in both the first and third years of marriage, money was most
      often reported as a topic of marital disagreement; tensions about leisure, each
      spouse's family of origin. and children were reported significantly less often;
      and tensions about religion were reported least often. Findings were very similar
      for African Americans and Euro-Americans, and for husbands and wives. Overall,
      findings show considerable stability in the relative frequency with which
      specific topics reportedly evoke tension early in marriage.

PMID- 12785623
TI  - Nations' rated individualism and suicide and homicide rates.
AB  - Individualism ratings for 27 nations were not associated with suicide or homicide
      rates after controls for per capita gross domestic product.

PMID- 12785624
TI  - A randomized trial of individual tutoring for elementary school children with
      reading and behavior difficulties.
AB  - Children in Grades K-5, selected for reading and behavior problems, received
      individual tutoring in a program which aimed to detail a hierarchy of reading
      skills, locate the point on the hierarchy at which each child should work, and
      provide enthusiastic social reinforcement for successes. Children were randomly
      assigned to higher or lower frequency tutoring (one 45-min. session every 1.6
      days vs every 8.3 days). The higher frequency group progressed significantly
      faster in reading than the lower frequency group. Both groups progressed much
      faster during the time of the intervention than they had before tutoring. Before
      tutoring, both groups had progressed at about 0.5 grade per year; during
      tutoring, the higher frequency group progressed at 1.5 grade per year and the
      lower frequency group at 1.1 grade per year. The subsets of children with verbal
      ability scores one or two standard deviations below the population mean, as
      assessed on the Peabody Picture Vocabulary Test, still progressed at average
      rates of 1.2 grade per year during tutoring. The amount of work students
      accomplished on a sounding and blending drill predicted reading progress. The
      intervention cost an average of 1,156 dollars per student per year.

PMID- 12785625
TI  - Attendance probabilities of participants in a human experiment.
AB  - This study investigated how different prompting strategies affected the
      attendance probabilities of 60 undergraduate students participating in an
      experiment. Subjects were randomly assigned to one of three conditions: no
      prompt, phone-message prompt, or phone-voice prompt. Analysis showed that
      participants in the no-prompt condition attended the study at a rate of 50%.
      Participants who received a phone-message prompt attended at a rate of 55%, while
      participants who received a phone-voice prompt attended at a rate of 100%.

PMID- 12785626
TI  - Comparison of textual analysis applied to two lectures written three years apart
      by one author: the language satellites.
AB  - A comparative textual analysis was carried out on two essays "Thanatol" and
      "Double Talk," by F. Perrier, which were originally lectures given three years
      apart by the author, a psychoanalyst. This study involved the use of the ALCESTE
      software program, a computer-assisted method of discourse analysis. It consists
      of modelling the distribution of the main words occurring in speeches or texts
      with a view toward identifying the repetitive language patterns most frequently
      used by a speaker or writer. This method is described in the first part of the
      paper. Various types of discourse emerged from analysis along with specific
      topics. There were three types in the case of Thanatol and four in that of Double
      Talk. Upon comparing the separate results obtained on each corpus, a pool of
      significant words observed in the corpus Thanatol was also present in Double
      Talk. These words were organised into groups called "language satellites" which
      were dispatched in the various types of discourse. Considering the underlying
      language structure (the enunciation), they formed another discourse running
      between the lines of two lectures. This supplementary discourse was recurrent and
      could be said to label the author and his thoughts. The ALCESTE method brings to
      light in the textual production of an author a recurrent pattern of discourse
      which might hold some clues for the analysis of texts and speech and even about
      the author as evident in his own ideas and thoughts.

PMID- 12785627
TI  - Boston Naming Test: problems with administration and scoring.
AB  - The poorly written administration and scoring instructions for the Boston Naming
      Test allow too wide a range of interpretations. Three different, seemingly
      correct interpretations of the scoring methods were compared. The results show
      that these methods can produce large differences in the total score.

PMID- 12785628
TI  - Further examination of the Self-efficacy Scale.
AB  - The purpose of this study was to examine further the factorial validity of the
      Self-efficacy Scale via component and subsequent correlational analyses. 651
      undergraduates enrolled in an introductory psychology course voluntarily
      completed the Self-efficacy Scale and the Bem Sex-role Inventory. A principal
      component analysis with an orthogonal rotation produced a two-factor solution
      which was remarkably similar to the factor structures reported previously. The
      two factors (General Self-efficacy and Social Self-efficacy) accounted for about
      34% of the total variance. Further, the correlation coefficients indicated that
      General Self-efficacy was more strongly related to masculine traits than to
      feminine traits, as defined by the Bem Sex-role Inventory.

PMID- 12785629
TI  - Maternal accommodation in infant-directed speech during mother's and twin
      infants' vocal interactions.
AB  - In this study a mother's instinctive accommodations of vocal fundamental
      frequency (f0) of infant-directed speech to two different infants was explored.
      Maternal speech directed to individual 3-mo.-old fraternal twin-infants was
      subjected to acoustic analysis. Natural samples of infant-directed speech were
      recorded at home. There were differences in the rate of infants' vocal responses.
      The mother changed her f0 and patterns of intonation contour when she spoke to
      each infant. When she spoke to the infant whose vocal response was less frequent
      than the other infant, she used a higher mean f0 and a rising intonation contour
      more than when she spoke to the other infant. The result suggested that the
      mother's speech characteristic is not inflexible and that the mother may use a
      higher f0 and rising contour as a strategy to elicit an infant's less frequent
      vocal response.

PMID- 12785630
TI  - Correlates of an ego-grasping attitude in Kuwaiti and American students.
AB  - In samples of American and Kuwaiti students, scores on an ego-grasping scale were
      associated with measures of psychopathology, the latter more strongly associated
      with ego-grasping scores for the American than the Kuwaiti sample.

PMID- 12785631
TI  - Lack of age differences in the Beck Depression Inventory-II scores of clinically
      depressed adolescent outpatients.
AB  - To assess whether the mean Beck Depression Inventory-II scores of adolescents who
      were diagnosed with unipolar depressive disorders differed with respect to age,
      the inventory was administered to 144 (60%) female and 96 (40%) male outpatients
      between 13 and 17 yr. who were diagnosed with depressive disorders. The internal
      consistency of the scores was high (coefficient alpha=.89). A factorial analysis
      of variance was used to test for the main effects of age, sex, ethnicity, type of
      depressive disorder, comorbidity, and the two-way interactions of age with the
      other main effects. The mean scores were not differentiated by age or by the
      interactions of age with the other effects. The lack of age differences in this 5
      year range on the mean scores of clinically depressed adolescents was discussed
      with respect to previous findings that have reported such differences in
      adolescents and adults.

PMID- 12785632
TI  - Motivation, altruism, and generalized compliance: a field study of organizational
      citizenship behaviors.
AB  - This study tests the relations among five sources of motivation and two
      organizational citizenship behaviors. 175 employees from 31 locations of two
      agriculturally based companies completed the Motivation Sources Inventory and
      were rated by their supervisors for demonstrated organizational citizenship
      behaviors. There were significant positive correlations for employees' Self
      concept-Internal Motivation with Altruistic Behavior of employees; while
      employees' Self-concept-External Motivation showed a significant negative
      relation with Altruistic Behavior by employees. Surprisingly, no correlation
      between employees' Goal Internalization Motivation and Altruistic Behavior by
      employees was found. Interpretation of these findings and further research are
      suggested.

PMID- 12785633
TI  - No sex difference in perceived competence of computer use among male and female
      college students in 2002.
AB  - The present research examined sex differences in general computer knowledge and
      computer anxiety. Survey data about computer knowledge, comfort, and interest
      were collected from 697 students, 579 from a previous study in 2001 at three
      types of colleges (a four-year liberal arts college, a business college, or a
      community college). With few exceptions, no differences associated with sex were
      detected. Implications for the present findings are discussed.

PMID- 12785634
TI  - Ethnic identity and psychosocial adjustment among international students.
AB  - A total of 118 international students studying in four different universities in
      the USA participated. Analyses indicated that search for ethnic identity and
      English proficiency predicted psychosocial adjustment. Students with higher
      English proficiency and students who understood the role of ethnic identity for
      themselves and showed commitment to learning more about their background also
      tended to report better adjustment.

PMID- 12785635
TI  - Perceptually oriented hypnosis.
AB  - This theoretical article explores postulates representative of a perceptual frame
      of reference for a better understanding of hypnotic experiencing. This author
      contends that Perceptual Psychology, a theory first conceptualized by Snygg and
      Combs, as revised by Combs, Richards, and Richards in 1988, and Perceptually
      Oriented Hypnosis provide an effective way of understanding hypnosis, the
      therapist-client relationship, and has some implications as well for better
      comprehending psychopathology. Perceptually oriented hypnotic principles are
      shown to enhance the characeristics of the adequate personality, expand the
      phenomenal field, change personal meanings, and change aspects of the phenomenal
      self in the context of hypnosis. Implications for understanding differing views
      and conflicting perceptions of reality held by scientists and researchers are
      discussed. Implications for Dissociative Identity Disorder are also addressed.
      Research utilizing Giorgi's research methodology and Wasicsko's qualitative
      procedure for assessing educators' dispositions is suggested.

PMID- 12785636
TI  - Smoking related to anxiety and depression in Greek medical staff.
AB  - We assessed the relation of anxiety and depression to smoking behavior in a
      sample of 80 physicians and surgeons, using the Spielberger State-Trait Anxiety
      Scale and the Beck Depression Inventory. 27 doctors were nonsmokers, 14 were
      former smokers, and 39 were current smokers. Current smokers showed significantly
      higher Anxiety and Depression scores compared to nonsmokers and former smokers,
      while the latter presented significantly lower Anxiety scores than nonsmokers. In
      current smokers, the daily quota of cigarettes was not correlated with Anxiety or
      Depression scores. From our results we can hypothesize that, among medical staff,
      smoking behavior is more anxiety-related than depression-related. In conclusion,
      we believe that interventions such as stress management techniques could be
      effective in lessening Anxiety and diminishing the need for relief searched for
      in smoking.

PMID- 12785637
TI  - Religiosity and conservatism revisited: relating a new religiosity measure to the
      two main conservative political ideologies.
AB  - The relation between the two religiosity dimensions which Wulff (1997) described
      (Exclusion vs Inclusion of Transcendence and Literal vs Symbolic) and two
      conservative political ideologies (Cultural and Economic Conservatism) was
      investigated in a sample of 714 students, a heterogeneous sample of 262 adults,
      and a sample of 301 religiously affiliated adults gathered in Flanders (Belgium).
      Both Exclusion vs Inclusion of Transcendence and Literal vs Symbolic were
      expected to relate only to Cultural Conservatism. Analysis supported these
      hypotheses, providing further evidence for the close association between
      religiosity and Cultural Conservatism and the validity of the Post-Critical
      Belief scale as a measure of Wulff's dimensions of religiosity.

PMID- 12785638
TI  - Associations of blood glucose control with self-efficacy and rated
      anxiety/depression in type II diabetes mellitus patients.
AB  - We investigated the possible relations of hemoglobin A1c (HbA1c) level, a
      parameter of blood glucose control with scores on anxiety, depression, and self
      efficacy for 113 outpatients (55 men and 58 women) with type II diabetes
      mellitus. The relation between the HbA1c level and the self-efficacy scores as
      well as with the ratings of anxiety and depression was evaluated. A significant
      relation was found for the HbA1c level with the scores; however, self-efficacy
      and anxiety and depression showed no association. These results suggest that
      HbA1c can be maintained at better levels by increasing self-efficacy of diabetic
      patients.

PMID- 12785639
TI  - Psychological correlates of optimism in college students.
AB  - This study assessed optimism held by 300 college students at a midwestern
      university using Scheier and Carver's Life Orientation Test. Optimism ratings
      were compared to measures of psychological functioning. Analysis showed that
      optimism was significantly associated with all of the adjustment measures
      (social, academic, personal, and goal commitment) assessed with Baker and Siryk's
      Student Adaptation to College Questionnaire, higher self-esteem measured with
      Rosenberg's Self-esteem scale, and with lower ratings of loneliness as assessed
      with the Revised UCLA Loneliness Scale.

PMID- 12785641
TI  - Empirical testing of the Satisfaction With Life Scale: a South African pilot
      study.
AB  - To explore applicability of the Satisfaction With Life Scale in a different
      racial and cultural context (South Africa), a questionnaire containing items on
      basic demographic characteristics, the 5-item Satisfaction With Life Scale, and
      the 10-item Rosenberg Self-esteem scale, was administered to a small convenient
      sample of 34 Black (13 men and 21 women) and 20 White (9 men and 11 women) South
      Africans aged between 17 and 70 years. As expected, Black respondents were less
      likely to have completed high school than White respondents and were more likely
      to be unemployed. Factor analysis of the Satisfaction With Life Scale
      (coefficient alpha of .92) yielded a single factor, accounting for 76% of the
      variance. Mean differences of the two groups were not significant when education
      and employment status were controlled. As anticipated, Life Satisfaction scores
      were correlated .86 with rated Self-esteem. Given the very small convenient
      sample, results are consistent with robust findings in western countries and
      encourage replication on a larger, representative sample.

PMID- 12785640
TI  - Construct validity of the Global Assessment of Functioning Scale for clients with
      anxiety disorder.
AB  - The Global Assessment of Functioning Scale is a widely used although poorly
      researched measurement of overall mental health or illness. This study
      investigated construct validity for clients with anxiety disorder. Analysis
      suggests that current suicidality was the most significant predictor of ratings.
      Current homicidality, work/school problems, and inability to care for oneself
      were not significantly correlated with scale ratings.

PMID- 12785642
TI  - Development and validation of an altruism scale for adults.
AB  - A new self-report scale, the Altruism Scale for Adults, of 28 items was
      developed. 14 items were from the Altruism subscale of Wrightsman's Philosophies
      of Human Nature Scale, and the other 14 items were newly constructed. The scale,
      anchored by 1: true or 2: false, was administered to 592 Korean men and women in
      eight subgroups. Cronbach alpha internal consistency was .89, and test-retest
      reliabilities (n = 52) over 1 and 5 wk. were .90 and .80, respectively. Campbell
      and Fiske's 1959 multitrait-multimethod analysis showed satisfactory convergent
      and discriminant validities. Overall results were promising for use of the scale
      in research and for practical purposes.

PMID- 12785644
TI  - Cross-cultural differences in female university students' attitudes toward
      homosexuals: a preliminary study.
AB  - 62 Caucasian, 61 Hispanic, and 44 Asian female undergraduates completed the Index
      of Homophobia by Hudson and Ricketts, seven items from the Attitudes Toward
      Lesbians and Gay Men Scale by Herek, and three questions on Affectional
      Orientation toward homosexuals from D'Augelli and Rose. Overall, familiarity with
      homosexuals as measured by self-reported number of homosexual friends correlated
      negatively with scores on the homophobia measures, but there were no significant
      differences among the groups' reported number of homosexual friends. Asian
      students scored significantly higher on the homophobia measures than Caucasian
      students. Both Asian and Hispanic students endorsed the statement significantly
      more often than Caucasian students that the university would be better if only
      heterosexuals attended. No significant differences in scores were found regarding
      attitudes toward lesbians versus gay men.

PMID- 12785643
TI  - Collective self-esteem data from four ethnic groups.
AB  - Collective self-esteem data were collected from 365 White, Black, Asian, and
      Hispanic undergraduates. Analyses of variance and intercorrelation matrixes were
      computed for each component of the scale. Asian and Hispanic groups showed higher
      scores on the Identity subscale than did the White and Black groups. In general
      the subscales were highly intercorrelated with the exception of the Identity
      component. Researchers should focus on the Identity component given its variation
      across groups and greater independence from the other subscales.

PMID- 12785645
TI  - Correlations for the Vineland Adaptive Behavior Scales with Kaufman Brief
      Intelligence Test in a forensic sample.
AB  - People with an intellectual disability are over-represented in the criminal
      justice system in many western countries. Identifying accused persons with
      intellectual disability is important if they are to receive protections available
      under the law. Accurate diagnosis is also relevant for correctional
      administrators, probation and parole services, and community services. Diagnosis
      of intellectual disability must be made on the basis of both cognitive skills
      (intelligence) and adaptive behavior. In this study, the Kaufman Brief
      Intelligence Test assessed intelligence, and the Vineland Adaptive Behavior
      Scales assessed adaptive behavior, through self-report. Tests were administered
      to 150 offenders, ranging in age from 13 to 53 years, in Australian prisons,
      juvenile detention centers, legal aid offices, and probation services. Pearson
      product-moment correlation coefficients calculated among all subtests and between
      total scores were significant. ROC curve analyses demonstrated that performance
      on each effectively predicted a standard score of less than 70 on the other one.

PMID- 12785646
TI  - Sex education sources and attitudes toward sexual precautions across a decade.
AB  - 75 college students responded to Moore and Barling's AIDS questionnaire.
      Coopersmith's Self-esteem Inventory, and a background survey regarding sex
      education and sexual and religious activity. The most commonly reported sources
      of sex education were peers, parents, and high school courses, respectively.
      Ratings of the most important of 10 potential sources of sex education included
      peers, high school courses, and religious institutions, respectively. None of
      these were significantly correlated with future condom use. Virgins reported more
      open communication with parents about sex. Sexual experience was positively
      related to more confusion about sexual precautions but negatively related to
      foreclosed attitudes toward such precautions. Some types of religious involvement
      (church attendance and campus religious organization membership) were related to
      foreclosed attitudes. Data in attitudinal and sex education were compared with
      data collected in 1991. Although students more frequently reported having
      received sex education in 2000, their attitudes toward utilizing sexual
      precautions have become somewhat more diffused.

PMID- 12785647
TI  - An MMPI-2 scale to identify reported history of emotional abuse.
AB  - A 42-item MMPI-2 scale classified 97.5% of 201 clinic outpatients into groups
      reporting or not reporting prior emotional abuse.

PMID- 12785648
TI  - Descriptive profile of sex and psychiatric diagnosis among rural and peri-urban
      clinic attenders in South Africa.
AB  - Of 1,232 patients receiving psychiatric medication in outlying areas of South
      Africa more than half had diagnoses of schizophrenia. Significantly more men than
      women had substance-induced psychosis, while significantly more women had
      depressive and anxiety disorders.

PMID- 12785649
TI  - Toward conceptual development and empirical measurement of global risk indicators
      in the lives of court-involved youth.
AB  - This paper reports work related to the conceptual development and empirical use
      of global risk indicators meant to measure rapidly and reliably potential threats
      to the overall development and well-being of adolescents in the juvenile justice
      system. The development of these indicators and initial data regarding their use
      with court involved samples are presented. Analysis of data gathered from a
      sample containing 248 families of adolescents who participated in a family-based
      diversion program identified a seven-factor structure that corresponded to
      theoretically derived dimensions of risk in domains associated with prior
      offenses, family/parenting, education/work, peers, substance use,
      personality/behavior problems, and attitudes/orientation. Analysis of data
      gathered from a second sample containing 373 families of adolescents who came
      into contact with the intake/diversion department of a county juvenile court
      confirmed the original seven factors of the battery and generated support for an
      eighth dimension composed of items that reflected leisure activities. The use of
      these global risk indicators are discussed as part of a practical and effective
      assessment battery for professionals working with court-involved youth and their
      families.

PMID- 12785650
TI  - PC versus Macintosh users.
AB  - In a sample of 78 university undergraduates, Macintosh users spent less time
      online than PC users and had more anxiety about computers.

PMID- 12785651
TI  - Factor structure of the Spielberger Anger Expression scales when used with
      Australian prisoners.
AB  - The State-Trait Anger Expression Inventory administered to prison inmates has
      supported the factor structure of the three anger expression scales although this
      structure has not been verified with Australian participants. Data collected from
      397 Western Australian male prisoners produced a factor structure consistent with
      the scale structure outlined in the 1991 manual. Scale means and standard
      deviations were similar to those reported for U.S. and Canadian prisoners. It is
      therefore appropriate to use the standard scoring procedures with Australian male
      prisoners.

PMID- 12785652
TI  - Relation of attitude toward body elimination to parenting style and attitude
      toward the body.
AB  - The purpose was to estimate the relation of attitude toward body elimination in
      93 college students (27 men and 66 women), to authoritarian personality features,
      participants' perception of their mothers' parenting style, and attitudes toward
      cleanliness, sex, and family nudity. Subjects were administered the Body
      Elimination Attitude Scale, the Four-item F Scale, the Parental Authority
      Questionnaire Pertaining to Mothers, and the items "Sex is dirty," "Cleanliness
      is next to godliness," and "Children should never see other family members nude."
      Larger scores for disgust toward body elimination were associated with
      authoritarian personality characteristics, being less likely to describe mother's
      parenting style as authoritative (open communication) and more likely to describe
      it as authoritarian and lower scores for tolerance for family nudity.
      Implications for further research were suggested.

PMID- 12785653
TI  - Empirical evaluation of the MCMI-III personality disorder scales.
AB  - The MCMI-III personality disorder scales were empirically validated with a sample
      of 870 clinical patients and inmates. Prevalence rates of personality disorders
      were in general lower on the MCMI-III than clinical ratings, but trait prevalence
      was generally higher; thus a base rate of 75 on the MCMI-III could be a guideline
      in the screening of trait prevalence. However, the sensitivity of some MCMI-III
      scales was very low. Moreover, the correlations of most personality disorder
      scales of the MCMI-III were significant and positive with corresponding measures
      on clinical ratings and MMPI-2 personality disorder scales, but these were, in
      general, not significantly higher than some other correlations. As a consequence
      the discriminant validity seems to be questionable. The MCMI-III alone cannot be
      used as a diagnostic inventory, but the test could be useful as a screening
      device as a part of a multimethod approach that allows aggregation over measures
      in making diagnostic decisions.

PMID- 12785654
TI  - Religious coping, drinking motivation, and sex.
AB  - The relations for religious coping with types of drinking motivation were
      examined in 178 college students. Participants completed the Ways of Religious
      Coping Scale and the Drinking Motives Questionnaire. As expected, correlations
      suggested that amount of alcohol used as well as social and enhancement motives
      for using were negatively related to religious coping scores. These relations
      were more clearly evident among women than among men. Coping motivation for
      alcohol use and religious coping were not significantly correlated.

PMID- 12785655
TI  - Environments, individual characteristics, and worry of young adults.
AB  - Relations were examined among distal and proximal learning contexts, individual
      characteristics, and the worry of young adults. Data were collected from 20-yr.
      old Australians (3,325 women and 3,070 men). Analysis suggested that learning
      environment and individual characteristic measures have significant associations
      with the worry of young adults and that the intensity of worry varies for young
      adults from different ethnic groups.

PMID- 12785656
TI  - Countertransference reactions toward specific client populations: a review of
      empirical literature.
AB  - Countertransference reactions can either benefit or hinder mental health
      professionals during the therapeutic process. An awareness of countertransference
      reactions can aid clinicians in understanding and anticipating their own specific
      emotional responses toward certain client populations. Recent empirical research
      suggests that common countertransference reactions may occur in mental health
      professionals when relating to certain client types. Since a literature review
      indicated that more numerous and reliable tests have been developed to measure
      countertransference during the past decade, as well as better research designs,
      this article reviews and summarizes all empirical research studies on
      countertransference reactions toward specific client populations during the past
      10 years, from 1990 to 2001.

PMID- 12785657
TI  - Differences between general computer attitudes and perceived computer attributes:
      development and validation of a scale.
AB  - The aim of this study was to develop a tool for measuring individuals'
      dispositions toward the use of computers in their work environment. The study
      reports the construction and validation of a general computer attitude and
      perceived computer attribute scale. Exploratory factor analytical evidence with a
      sample of 381 employees indicated a structure underpinned by two constructs, an
      attitudinal factor and a perceived computer attribute factor. The internal
      consistency estimates of reliability of scores were .81 for the attitudinal
      factor and .89 for the perceived computer attribute factor. Compared to the
      computer attitude subscale, scores on the perceived computer attribute subscale
      correlated higher with computer experience and professional computer use within
      the sample.

PMID- 12785658
TI  - Tridimensional personality traits of college student marijuana users.
AB  - The present study examined the possibility that marijuana use among college
      students might be associated with particular personality traits. College student
      volunteers (N = 176) were administered the Tridimensional Personality
      Questionnaire and a drug-use questionnaire. Analysis of variance showed that the
      mean score on Novelty Seeking was significantly higher and on Persistence
      significantly lower among lifetime marijuana users than among nonmarijuana using
      peers. Programs for prevention among college students may be enhanced by
      approaches tailored to individuals scoring high on Novelty Seeking and low on
      Persistence.

PMID- 12785659
TI  - Psychological symptoms and competence at three organizational levels of
      industrial design: the main and moderating role of sense of coherence.
AB  - This study investigated the role of the sense of coherence in occupational well
      being at three organizational positions of industrial designing (top-level
      designers, designers, and assisting personnel). In a sample of 422 industrial
      design personnel, sense of coherence was positively related to competence and
      negatively to psychological symptoms. It also moderated the relation of autonomy
      to competence and psychological symptoms but more strongly among the designers
      and the assisting personnel than among the top-level designers. Analysis showed
      autonomy was beneficial for individuals who also had high scores on sense of
      coherence. Longitudinal studies are needed on the role of sense of coherence as
      regards the psychological health of different subgroups.

PMID- 12785660
TI  - The Guilty Knowledge Test and the modified Stroop task in detection of deception:
      an exploratory study.
AB  - The current study tested whether a simple Stroop paradigm can be used to detect
      deceptive behavior. 40 university students (34 women), half of whom committed a
      mock crime, were administered a Guilty Knowledge Test and modified Stroop task to
      detect guilt or innocence. The Guilty Knowledge Test is a well-known
      psychophysiological detection method, which consists of multiple-choice questions
      about details of the crime while skin conductance is recorded. Subjects
      possessing guilty knowledge are expected to show enhanced differential responses
      to the relevant stimuli. The modified Stroop task required color-naming of
      colored words related to the mock crime or an irrelevant crime. Each version of
      the Stroop task was presented in story form. Subjects possessing guilty knowledge
      were expected to produce larger reaction times to the relevant version relative
      to the irrelevant version. The test correctly identified 100% of innocent
      participants and 78% of guilty participants. In contrast, Stroop interference.
      i.e., reaction times for irrelevant crime details subtracted from those for mock
      crime details, did not differentiate between the two groups, suggesting that the
      story form of the Stroop paradigm is not suitable for lie detection.

PMID- 12785661
TI  - One obvious reason doctoral programs in psychology use the Graduate Record
      Examination.
AB  - Given that most doctoral programs in psychology have more applicants than
      openings, it is understandable that programs would focus on higher GRE scores
      which predict program completion better than lower scores.

PMID- 12785662
TI  - Effects of sex on raters' accountability.
AB  - The effects of sex (rater and ratee) on raters' accountability in the context of
      performance appraisal were investigated. The 130 participating undergraduates
      (men and women) rated a fictitious male or female's performance on a clerical
      task subsequent to receiving self-assessment information. As expected, raters'
      knowledge of a high self-assessment was followed by significantly higher
      performance ratings than after knowledge of a low self-assessment. Contrary to
      expectations, no differences were found for either raters' or ratees' sex. The
      results suggest that the sex of the rater or ratee is not associated with raters'
      accountability.

PMID- 12785663
TI  - Establishing worker identity: a study of people in craft work.
AB  - Having a work-related identity is central to being an adult in America. Going to
      work and engaging in prescribed work behaviors in the workplace is the usual or
      typical way that adults achieve worker identities. The purpose of this study,
      developed from an ethnography of people who make crafts at home and sell their
      work at craft fairs, was to examine how worker identity is constructed when
      individuals do not have the external markers of a socially identified job and
      workplace. I used participant observation of craft fairs and other craft venues,
      and interviews of people who do this work, as major sources of data. Results of
      the analysis of the data related to worker identity demonstrated that these
      crafters followed basic steps, or rules, to achieve such a worker identity. These
      rules, some for work at home and some for other social contexts, encompassed
      complex behaviors learned through the process of doing the work as well as from
      other crafters. The conclusions of the study are first, that individual and
      social identity formation as a worker involves complex processes for which rules
      and guidelines do exist. Second, these rules are often discovered through the
      process of doing the work. Third, the meaning of work and the individual and
      social identities of being a worker are individual, and finally, knowledge of
      worker identity formation is gained through the study of both those who
      successfully achieve such an identity and those who do not.

PMID- 12785664
TI  - The meaning of the working cooperative for persons with long-term mental illness:
      a phenomenological study.
AB  - OBJECTIVE: The objective of this phenomenological study was to understand the
      meanings of the lived experiences of persons with long-term mental illness at a
      social working cooperative. METHOD: Eighteen participants were interviewed either
      two or three times while participating in a working cooperative in a community
      psychosocial rehabilitation program. Data were analyzed and interpreted using the
      Empirical, Phenomenological, Psychological (EPP) method (Karlsson, 1993).
      RESULTS: The findings revealed a meaning-structure consisting of one main
      constituent that characterized the cooperative as a normalizing life-world. Three
      phases contributed to the normalization process. In the first phase the
      participants experienced a shift from an unsatisfying occupational context to an
      enriching occupational life-world. In the second phase participants had the
      possibility to satisfy some of their occupational and social needs. During this
      phase, experiences of being productive and needed, commitment to others,
      development of their skills, and competence in work tasks and social activities
      were expressed, all of which contributed to personal growth and a more positive
      view of self. In the third phase, the meaning of the cooperative changed for some
      participants, who expressed this through their readiness to leave and take a
      further step into the life-world outside the cooperative. CONCLUSION: The study
      emphasizes that the cooperative is an important alternative to employment for
      participants with severe mental illness who do not have the capacity to be
      employed in the community or who do not want to leave the life-world of the
      cooperative that gives them pride, joy, and satisfaction.

PMID- 12785665
TI  - Play in Mayan children.
AB  - OBJECTIVE: The purpose of this study was to describe the characteristics of play
      activities and playfulness in a group of Mayan children in southern Belize.
      METHOD: This qualitative study involved participant observation in the daily
      occupations of 20 children from five Mayan families over a 2-week period.
      Analysis of the field notes, using open and closed coding, revealed themes
      specific to customs of child rearing, play activities, and playfulness. FINDINGS:
      The primacy of adult work is a major cultural principle that influences Mayan
      children's daily occupations. Parents did not encourage play but permitted play
      if it did not interfere with work. Children found ways to integrate play
      activities and playfulness into their daily occupations. CONCLUSION: The
      statement, "play is a child's major occupation," may not be a universally held
      belief. Parental values and customs of child rearing should be considered in
      order to provide culturally sensitive and relevant services.

PMID- 12785666
TI  - Pencil grips, legibility, and speed of fourth-graders' writing in cursive.
AB  - OBJECTIVE: The purpose of this research was to study how the speed and legibility
      of fourth-graders handwriting was affected by type of pencil grip on the
      Evaluation Tool of Children's Handwriting-Cursive. METHOD: Ninety-five typically
      developing students and 6 students receiving special education services completed
      the Evaluation Tool of Children's Handwriting-Cursive (ETCH-C). Photographs were
      taken of their pencil grips while they wrote the alphabet. One-way ANOVAs were
      calculated to compare legibility rates and writing speeds by type of pencil grip.
      RESULTS: Ninety-nine of the students used one of four pencil grips including the
      dynamic tripod (38 students), the dynamic quadrupod (18), the lateral tripod
      (22), and the lateral quadrupod (21). One student used the four-finger pencil
      grip and one used the interdigital pencil grip. Mean cursive writing speeds were
      similar for all pencil grips except for the interdigital grasp. Speeds obtained
      were slower than recently published fourth-grade speeds ranging from a mean of
      29.45 to 34.75 letters per minute. CONCLUSION. This study found the lateral
      quadrupod and four-finger pencil grips to be as functional as the dynamic tripod,
      lateral tripod, and dynamic quadrupod pencil grips. This study provides average
      handwriting speeds for fourth-grade students on the ETCH-C.

PMID- 12785667
TI  - Comparison of motor self-regulatory and stress behaviors of preterm infants
      across body positions.
AB  - Occupational therapists working with infants in neonatal intensive care units
      (NICUs) make positioning recommendations to optimize self-regulation, with little
      published data supporting this practice. In this retrospective descriptive study,
      15 hospitalized preterm infants (M(gestational age) = 32 weeks) were videotaped
      during non-caregiving periods in order to record the frequency of specific
      behaviors in relation to six infant positions (prone nested, prone un-nested,
      side-lying nested, side-lying un-nested, supine nested, and supine un-nested).
      Behaviors coded were those that suggest infant stress or motor efforts at self
      regulation, as defined for the original study. Mixed effects regressions and post
      hoc Tukey Honestly Significant Difference tests were used to analyze the data,
      after the calculation of a ratio of the number of behaviors in each position.
      Higher ratio values reflect a greater occurrence of behaviors. The number of
      motor self-regulatory and stress behaviors were related to infant position, with
      the highest ratios of behaviors observed in side-lying un-nested and the lowest
      in prone nested. Behavior ratios did not differ between prone un-nested and prone
      nested, nor between supine un-nested and supine nested. More self-regulatory and
      stress behaviors were related to longer periods of fussing and crying. Longer
      periods of light sleep were related to fewer stress behaviors. Infants performed
      the fewest stress behaviors in prone nested, prone un-nested, or side-lying
      nested. These positions may benefit infants in the NICU by reducing the need for
      motor-based self-regulatory behaviors and potentially conserving energy for
      growth.

PMID- 12785668
TI  - After rehabilitation: an 18-month follow-up of elderly inner-city women.
AB  - OBJECTIVE: Elderly inner-city women (n = 125) greater than the age of 60 and
      living alone and who were consecutively admitted to a large, urban, university
      based rehabilitation hospital were followed to (a) examine the power of
      standardized clinical measures to predict who was living alone 18 months after
      discharge, (b) determine whether live-alone women at 18 months' follow-up were
      more independent in instrumental activities of daily living (IADL) than women who
      were not living alone, and (c) investigate whether women who return home to live
      alone and have low or declining physical function are at risk for subsequent
      relocation or death. METHOD: Data from four standardized assessments (physical
      function, cognition, comorbidity, and depression) and demographic information
      were gathered during in-patient rehabilitation. Self-report IADL data were
      collected via telephone interviews at 3, 6, and 18 months' follow-up. RESULTS:
      Statistical analysis of results showed that physical function, cognition, and
      comorbidity were significant and independent predictors of living alone at 18
      months' follow-up. Women living alone at 18 months reported significantly greater
      IADL independence than women who were not living alone. Path analysis confirmed
      that the relationship between the clinical measures and living situation at 18
      months was mediated by self-reported IADL functioning. CONCLUSION: Standard
      clinical data obtained at discharge are useful to identify who can return home to
      live alone after rehabilitation, but in-home assessment of IADL remains key to
      understanding the complex skills required to live alone.

PMID- 12785669
TI  - Occupational therapists' responses to practice errors in physical rehabilitation
      settings.
AB  - OBJECTIVE: Errors occur in all health care professions. Practice errors, however,
      have not been systematically examined in occupational therapy. The purpose of
      this study was to examine occupational therapists' responses to practice errors
      in physical rehabilitation settings. METHOD: A qualitative focus group research
      method was used in this study and a total of 35 occupational therapists from four
      different states who had practice experience in physical rehabilitation settings
      participated in four focus groups. Focus group discussions were transcribed
      verbatim and analyzed by two investigators of the study. Qualitative software
      program, NUD*IST Vivo was used to aid the data analysis process. RESULTS: Five
      major themes were generated from the data regarding practice errors, which
      included (1) Concept of practice error: It is against our standards; (2)
      Perceived causes of practice error: Not just an individual matter; (3) Emotional
      responses: I felt horrible; (4) Impact on practice: Doing things differently; and
      (5) Management of practice error: Being honest and taking initiative.
      Occupational therapists perceived practice error from a broad perspective and
      identified physical and psychosocial issues as practice error. CONCLUSION: Most
      practice errors described by participants appeared to be preventable. Despite the
      tremendous emotional distress in reaction to making an error, participants valued
      the learning in the experience and made constructive practice changes. Findings
      of the study have implications for current educational training programs and
      practice such as the development of clinical reasoning related to patient safety
      and assertiveness training for hierarchical situations.

PMID- 12785670
TI  - Effects of an energy conservation course on fatigue impact for persons with
      progressive multiple sclerosis.
AB  - OBJECTIVE: Fatigue is a common, troublesome symptom for persons with multiple
      sclerosis. This study evaluated the effects of an energy conservation course on
      fatigue impact for persons with multiple sclerosis whose symptoms cause moderate
      to severe disability. METHODS: Thirty-seven persons with progressive multiple
      sclerosis participated in an 8-week experimental energy conservation course
      treatment and an 8-week control period of traditional treatment using a crossover
      design. The Fatigue Impact Scale (FIS) was used to assess fatigue impact before
      and after the experimental and control periods, and 8 weeks post-energy
      conservation course. RESULTS: After participation in the energy conservation
      course, the average FIS total score and physical, cognitive, and psychosocial
      subscale scores decreased significantly, whereas the total and subscale scores
      did not change significantly during the control period. Additionally, decreased
      fatigue impact was maintained 8 weeks after course completion for evaluated
      participants. CONCLUSION: This study provides evidence that this energy
      conservation course can be a beneficial intervention for persons with progressive
      multiple sclerosis.

PMID- 12785672
TI  - Qualitative and quantitative knowledge of results: effects on motor learning.
AB  - OBJECTIVE: This study investigated the effects of qualitative and quantitative
      knowledge of results (KR) on the acquisition of a motor skill. It was
      hypothesized that there would be differences in performance during skill
      acquisition and retention, depending on the type of feedback given. Qualitative
      KR was in the form of verbal encouragement and quantitative KR was in the form of
      an algebraic number representing an error score. METHODS: Seventy-seven adults
      were randomly assigned to one of four feedback conditions, Quantitative,
      Qualitative, Quantitative and Qualitative, and no feedback (Control).
      Participants learned an isometric force production skill. Data were collected
      during skill acquisition and retention phases. Computer hardware and custom
      software were used to collect data and administer the feedback conditions of the
      independent variable. RESULTS: There was a statistically significant difference
      in the Acquisition Phase for the main effect of Condition F(3,73) = 6.35, p <
      .05, and for Block F(9,657) = 2.07, p < .05, but there was no statistically
      significant Condition X Block interaction F(27,657) = 1.02, p > .05. Pair-wise
      comparisons revealed statistically significant differences between conditions
      containing qualitative feedback and conditions containing no qualitative feedback
      (p < .05). The main effect of condition was significant F(3,73) = 3.00, p < .05
      in the retention phase, however there were no significant pair-wise comparisons
      (p > .05). CONCLUSION: The results of this study suggest that in a healthy adult
      population, qualitative feedback, by itself and when combined with quantitative
      feedback, resulted in superior skill acquisition, but not in the retention of
      that skill. The artificiality of the task along with differing modes of feedback
      (audible versus visual) are two potentially limiting factors to this study.
      Future research that controls for these factors may yield more definitive
      findings about the role that qualitative feedback has in improving motor
      performance and learning.

PMID- 12785671
TI  - Validation of a driving simulator by measuring the visual attention skill of
      older adult drivers.
AB  - OBJECTIVE: The purpose of this study was to validate a laboratory-based driving
      simulator as an off-road screening tool for older adult drivers by measuring
      their visual attention skill, and to determine how the visual attention skill
      changes across time in a 45-minute simulated driving test. METHOD: One hundred
      and twenty-nine community-dwelling older drivers volunteered to take part in the
      study. A range of driving scenarios was devised and implemented in a simulator
      setting to assess the driving skills of the participants. Visual attention skill,
      an important contributing factor to motor vehicle crashes, was assessed by the
      participant's reaction times to a sequence of 14 visual stimuli during the
      primary task of sustained driving. Repeated measures of analysis of variance
      (ANOVA) were undertaken to determine the effects of age and gender on the visual
      attention skill. Trend analysis was performed to investigate how repeated
      exposures to the visual stimulus affected the reaction time. RESULTS: The visual
      attention skill of older drivers was found to decline with age (F(1,126)) =
      42.52, p value = 0.002), whereas the effect of gender was not significant.
      Participants increased their speed of reaction times for the first half of the
      testing then slowed down during the second half. CONCLUSION: That visual
      attention skill declined with age was consistent with the literature, and
      validated the driving simulator as an effective screening tool for older adult
      drivers. With rapid advancements in computer technology, the driving simulator
      will likely play an important role in assisting occupational therapists with off
      road assessment of older drivers.

PMID- 12785673
TI  - Perceptions regarding school-based occupational therapy for children with
      emotional disturbances.
AB  - The purpose of this study was to identify the perceived appropriateness, extent,
      and types of services provided by occupational therapists to children with
      emotional disturbances in public schools. A nationally mailed survey was
      conducted of randomly selected school occupational therapists derived from the
      American Occupational Therapy Association School System Special Interest Section
      list. The sampling frame was 982 with a response rate of 48% (n = 476). Eighty
      seven percent of all respondents were supportive of school occupational therapy
      for students with emotional disturbances, although these students made up only a
      small proportion of their caseload. The therapists indicated that a variety of
      intervention approaches were used with most targeting educational areas,
      especially handwriting. The most commonly reported intervention was sensory
      integration. Many respondents perceived that they could not provide effective
      interventions because they were not appropriately trained. Perceived lack of
      knowledge and confusion about occupational therapy's role may lead to
      underutilization of occupational therapy for addressing the complex needs of
      children with emotional disturbances. Further research and discussion are needed
      in the profession to arrive at consensus regarding what approaches are most
      appropriate and effective in schools.

PMID- 12785674
TI  - Adolescent performance on the Allen Cognitive Levels Screen.
AB  - OBJECTIVE: The purpose of this study was to provide information regarding the
      validity of using the Allen Cognitive Levels Screen (ACL-90 version) by comparing
      functional cognitive performance between adolescents living in the community and
      adolescents residing in mental health facilities. METHOD: Sixty-three adolescents
      were assessed using the ACL-90: 32 adolescents living in the community, and 28
      adolescents residing in residential mental health facilities. RESULTS: Using a
      one-tailed t test, performance scores for adolescents residing in the community
      were statistically higher than those for adolescents living in residential mental
      health facilities (t(34) = 4.3, p < .001). CONCLUSION: This study suggests the
      validity of the ACL-90 as an assessment to use for screening the cognitive
      functional performance of adolescents.

PMID- 12785675
TI  - Occupation-based and family-centered care: a challenge for current practice.

PMID- 12785676
TI  - Challenging the rhetoric and reality: only an individual and systemic approach
      will work for evidence-based occupational therapy.

PMID- 12785677
TI  - Mycobacterium avium subspecies paratuberculosis: a review of current knowledge.
AB  - Although Mycobacterium avium subsp. paratuberculosis infection has had its
      greatest effect on domestic agricultural animal species, it can also have a
      significant impact on wildlife species. More cases of infection are being
      reported, and because of its ability to elude immunologic control and to persist
      in the environment, M. paratuberculosis may spread within and among captive and
      free-ranging wildlife populations in the absence of organized control programs.
      Studies to improve our ability to detect the organism in biologic samples such as
      milk, blood, and manure through immunomagnetic separation, automated culture
      methods, and improved polymerase chain reaction procedures are underway in
      several countries. Studies of the organism's genetic components, virulence
      factors, and antigens support the development of new diagnostic tools and
      vaccines.

PMID- 12785678
TI  - Corneal lipid deposition in Cuban tree frogs (Osteopilus septentrionalis) and its
      relationship to serum lipids: an experimental study.
AB  - To evaluate the association between corneal lipid infiltration (corneal arcus)
      and dietary cholesterol in Cuban tree frogs (Osteopilus septentrionalis), 47 wild
      caught frogs were fed diets of either regular or high-cholesterol crickets
      containing 0.7% and 1.7% cholesterol dry matter, respectively. Serum total
      cholesterol and triglycerides were measured when the frogs were euthanized after
      17 mo. In a subsample of frogs, serum lipoproteins were characterized using high
      performance liquid chromatography. The first case of corneal lipid deposition
      occurred in a female frog after 13 mo on the high-cholesterol diet. In the
      subsequent 4 mo, 5/11 males and 11/35 females developed the disease. Four of
      these affected frogs were females on the regular diet. Frogs with corneal lipid
      deposition had elevated serum total cholesterol (27.3 +/- 19.8 mmol/L) and low
      density lipoproteins (LDL, 17.8 +/- 18.9 mmol/L) compared with unaffected captive
      frogs (16.5 +/- 20.4 and 9.0 +/- 7.6 mmol/L, respectively). Corneal lipid
      deposition was more prevalent in frogs on the high-cholesterol diet, and this
      group had higher serum total cholesterol (34.1 +/- 15.2 mmol/L in females, 22.8
      +/- 14.8 mmol/L in males) than did frogs on the diet of regular crickets (12.3 +/
      8.7 mmol/L in females, 10.4 +/- 3.1 mmol/L in males). Captive frogs on both
      diets had higher serum total cholesterol than did wild frogs (3.1 +/- 2.1 mmo/L
      in females, 5.3 +/- 2.6 mmo/L in males). This additional serum cholesterol was
      primarily carried on very low-density lipoproteins (VLDL) and LDL rather than
      high-density lipoproteins (HDL), as indicated by the significantly higher ratio
      of VLDL cholesterol and LDL cholesterol over HDL cholesterol in captive frogs
      compared with wild frogs. Elevation in this ratio was significantly higher in
      captive females than in captive males. There was no evidence that increased serum
      cholesterol in captive females was directly related to the process of
      vitellogenesis.

PMID- 12785679
TI  - Infectious disease serologic survey in free-ranging Venezuelan anacondas
      (Eunectes murinus).
AB  - Reptiles can harbor pathogenic microorganisms asymptomatically and serve as
      potential reservoirs of infection for humans, domestic animals, and other
      reptiles. Infectious diseases are also problematic for free-ranging reptile
      populations and are an important consideration in reptile reintroduction and
      translocation projects. There have been limited serologic studies of free-ranging
      reptiles for evidence of exposure to potential pathogens. In the present study,
      serum or plasma samples from five male and five female free-ranging Venezuelan
      anacondas (Eunectes murinus) were screened for antibodies to eastern, western,
      and Venezuelan equine encephalitis viruses, vesicular stomatitis virus, ophidian
      paramyxovirus, 19 Leptospira interrogans serovars, and Cryptosporidium serpentes.
      Antibodies to these agents were not detected, or antibody titers were low and
      possibly nonspecific. These results for the limited number of anacondas surveyed
      suggest that they do not serve as significant reservoirs for these infectious
      agents at this location.

PMID- 12785680
TI  - Irradiation of diets fed to captive exotic felids: microbial destruction,
      consumption, and fecal consistency.
AB  - Two frozen, raw horse meat-based diets fed to captive exotic felids at Brookfield
      Zoo were irradiated to determine the extent of microbial destruction and whether
      radiation treatment would affect consumption and/or fecal consistency in exotic
      cats. Fifteen cats, two African lions (Panthera leo), two Amur tigers (Panthera
      tigris altaica), one Amur leopard (Panthera pardus orientalis), two clouded
      leopards (Neofelis nebulosa), two caracals (Felis caracal), one bobcat (Felis
      rufus), and five fishing cats (Felis viverrinus), housed at Brookfield Zoo were
      fed nonirradiated and irradiated raw diets containing horse meat with cereal
      products and fortified with nutrients: Nebraska Brand Feline and/or Canine Diet
      (Animal Spectrum, North Platte, Nebraska 69103, USA). Baseline data were obtained
      during a 2-wk control period (nonirradiated diets), which was followed by a 4-wk
      period of feeding comparable irradiated diets. Feed intake and fecal consistency
      data were collected. An estimated radiation dose range of 0.5-3.9 kilograys
      reduced most microbial populations, depending on specific diet and microbe type.
      Irradiation had no overall effect on either feed consumption or fecal consistency
      in captive exotic cats, regardless of species, age, sex, or body mass. Data
      indicate that irradiation of frozen horse meat-based diets (packaged in 2.2-kg
      portions) result in microbial destruction in these products but that product
      storage time between irradiation and sampling may also affect microbial
      reduction. However, irradiation would be an appropriate method for reducing
      potentially pathologic bacteria in raw meat fed to exotic cats.

PMID- 12785681
TI  - Evaluation of long-term sedation in cheetah (Acinonyx jubatus) with perphenazine
      enanthate and zuclopenthixol acetate.
AB  - Two long-acting neuroleptics were used to tranquilize nine captive cheetahs
      (Acinonyx jubatus). Perphenazine enanthate (3.0 mg/kg) and zuclopenthixol acetate
      (0.6 mg/kg) were each administered to separate groups of three cheetahs in a
      double blind trial. Both products were administered together to a third group of
      three animals at the same dosages. Behavioral effect, duration of effect, and
      possible side effects were observed by a predefined protocol. Under standardized
      holding conditions, the cheetahs were observed 5 days before drug administration
      and 14 days after administration. Daily activity was defined and statistically
      evaluated by a U-test. A significant reduction of activity was observed after
      administration in all three trials. Zuclopenthixol acetate at 0.6 mg/kg alone and
      in combination with perphenazine enanthate caused inappetence, ataxia, extra
      pyramidal reactions, akathisia, and prolapse of the third eyelid. Zuclopenthixol
      acetate should not be used in cheetahs. Perphenazine enanthate did not cause
      inappetence, reduced appetite, or any of the previously mentioned side effects
      when used alone. It produced satisfactory tranquilization and is suitable and
      safe for cheetahs at 3.0 mg/kg. This dosage should be varied depending on health,
      age, and temperament of the individual cheetah.

PMID- 12785683
TI  - The requirement for natural sunlight to prevent vitamin D deficiency in iguanian
      lizards.
AB  - To investigate possible causes of embryonic and neonatal mortality in a group of
      captive Fijian iguanas (Brachylophus fasciatus and Brachylophus vitiensis), the
      vitamin D status of adults in the colony was compared with that of agamid and
      iguanid lizards either housed in indoor enclosures under artificial ultraviolet
      light or exposed to natural sunlight (wild-caught or captive animals housed
      outdoors). Those under artificial lighting had a significantly lower vitamin D
      status than those housed exclusively outdoors, whereas the vitamin D status of
      Fijian iguanas that had received intermittent exposure to natural sunlight was
      intermediate and not significantly different from that of animals housed
      exclusively outdoors. However, eggs from some of these Fijian iguanas had
      substantially lower vitamin D content than eggs from outdoor iguanid and agamid
      animals. Artificial ultraviolet light, therefore, might not be an adequate
      substitute for natural sunlight to maintain vitamin D status of lizards. This
      possible inadequacy may be because either artificial ultraviolet light has a
      lower intensity of the wavelengths that induce vitamin D than does sunlight or
      the intensity of the artificial lighting is not sufficient.

PMID- 12785682
TI  - Procedure for successful interspecific embryo transfer from mouflon (Ovis gmelini
      musimon) to Spanish Merino sheep (Ovis aries).
AB  - Embryos from five anesthetized mouflons (Ovis gmelini musimon), superovulated
      with FSH-o (Ovagen) were transferred into preselected Spanish Merino sheep (Ovis
      aries). Myorelaxation was complete in four of five donor mouflons. The status of
      the uterus of potential recipients was evaluated by transrectal ultrasonography,
      and those ewes with fluid in the uterine horn were rejected. The corpus luteum in
      each ewe was assessed ultrasonographically the day before surgery. Plasma
      progesterone levels and the quality of the corpora lutea were the criteria for
      selection of recipients. Ten embryos were transferred to the five selected
      Spanish Merino recipients, resulting in four pregnancies and seven live-born
      lambs, including three sets of twins. This study shows that determination of
      plasma progesterone levels combined with ultrasonographic assessment of the
      corpus luteum provides information useful for screening of potential recipients.

PMID- 12785684
TI  - Toxoplasma gondii antibodies in exotic wild felids from Brazilian zoos.
AB  - Serum samples from 37 captive exotic felids in 12 zoos from six Brazilian states
      were assayed for antibodies to Toxoplasma gondii by the modified agglutination
      test using formalin-fixed whole tachyzoites. Titers greater than or equal to 1:20
      were considered positive. Antibodies to T. gondii were found in 24 of 37 (64.9%)
      felids, including one European lynx (Lynx lynx), two jungle cats (Felis chaus),
      two servals (Leptailurus serval), two tigers (Panthera tigris), three leopards
      (Panthera pardus), and 14 of 27 lions (Panthera leo). This is the first serologic
      analysis for T. gondii infection in exotic wild felids from Brazilian zoos.

PMID- 12785685
TI  - Pulmonary candidiasis caused by Candida albicans in a Greek tortoise (Testudo
      graeca) and treatment with intrapulmonary amphotericin B.
AB  - An adult female Greek tortoise (Testudo graeca) presented with dyspnea, lethargy,
      and anorexia. Severe unilateral pulmonary candidiasis was diagnosed and confirmed
      by histologic and microbiologic evaluations. Initial treatment with ketoconazole
      resulted in plasma elevations of aspartate aminotransferase, lactate
      dehydrogenase, and bile acids consistent with imidazole-induced hepatotoxicity.
      Plasma chemistry abnormalities resolved upon withdrawal of the drug. Temporary
      osteotomy permitted access to the diseased lung and facilitated intrapulmonary
      catheterization. Intrapulmonary amphotericin B therapy at 0.1 mg/kg s.i.d. for 34
      days proved to be both safe and effective in this case.

PMID- 12785686
TI  - Meningoencephalitis in a Boelen's python (Morelia boeleni) associated with
      paramyxovirus infection.
AB  - An adult male Boelen's python, Morelia boeleni, presented with acute neurologic
      disease and was euthanatized. Histologic examination revealed nonsuppurative
      meningoencephalitis. Occasional eosinophilic intracytoplasmic inclusions were
      noted in glial cells. On the basis of clinical signs and histopathology,
      inclusion body disease of boid snakes was suspected, but inclusions were not seen
      in other organs commonly affected with the disease. Moreover, electron microscopy
      revealed that the inclusions contained stacks of filaments 13-14 nm wide. With
      the use of a generic paramyxovirus cDNA probe, sections of brain and esophageal
      ganglion demonstrated hybridization. The findings indicate that paramyxovirus was
      the likely cause of the encephalomyelitis in this python, and this virus should
      be included in the differential diagnosis of pythons exhibiting central nervous
      system disease.

PMID- 12785687
TI  - Monitoring pregnancy in babirusa (Babyrousa babyrussa) with transabdominal
      ultrasonography.
AB  - This case report documents the application of transabdominal ultrasonography for
      detecting pregnancy and monitoring fetal development in an unanesthetized,
      unrestrained babirusa (Babyrousa babyrussa). A 4-yr-old multiparous female
      babirusa was trained to accept monitoring via transabdominal ultrasonography on a
      weekly basis postcoitus. Uterine changes associated with pregnancy were first
      detected at 30 days gestation. Three fetuses were first visualized on day 38, and
      two of the three fetuses were detectable until term. One fetus failed to develop
      and appeared to be resorbed between days 80 and 94 of the 161-day pregnancy. The
      growth of the remaining two fetuses was monitored via cranial measurements taken
      during the weekly scans throughout the pregnancy. By monitoring a subsequent
      pregnancy via ultrasound in the same female it was possible to confirm her
      tendency towards partial resorption, with earliest detection of uterine changes
      on day 32 and apparent resorption of one of three fetuses at approximately the
      midpoint of gestation. Two rectal scans of a different female under anesthesia at
      28 and 50 days gestation showed stages of development comparable to those
      visualized transabdominally. However, the transabdominal scans produced better
      images of the reproductive tract, perhaps because of the close proximity of the
      pregnant uterus to the abdominal wall.

PMID- 12785688
TI  - Presumptive copper deficiency in hand-reared captive pronghorn (Antilocapra
      americana) fawns.
AB  - Presumptive copper deficiency was diagnosed in hand-reared captive pronghorn
      (Antilocapra americana) at the Los Angeles Zoo. Clinical signs, which were
      manifested in growing fawns, included anemia, anorexia, diarrhea, progressive
      paresis/recumbency, and aortic rupture. The range of serum copper concentrations
      in fawns born during the 1989 season (0.08-0.67 ppm) was below levels considered
      normal for domestic sheep and goats (0.7-2.0 ppm) and below concentrations
      measured in adult pronghorn (0.4-1.43 ppm). Copper sulfate supplementation of the
      hand-rearing formula, which was initiated in 1989, resulted in a significant
      increase in mean (+/- SD) serum copper levels from 0.45 +/- 0.18 ppm before
      supplementation to 0.68 +/- 0.05 ppm after supplementation (P < 0.05). Fawns born
      in subsequent seasons (April 1990-August 1993) continued to be supplemented with
      copper in the hand-rearing formula. Mean serum copper concentration from these
      fawns (0.68 +/- 0.22 ppm) was similar to the mean values from supplemented 1989
      fawns and adult pronghorn in this herd (0.85 +/- 0.34 ppm; P > 0.05). No clinical
      signs of copper deficiency were detected in any fawns after supplementation was
      started. Analyses of the herd's diet revealed marginal dietary copper levels.
      Suspected dietary deficiency was confirmed by marginal tissue and serum copper
      concentrations in some of the herd's adult animals. Dietary copper levels were
      corrected to prevent future cases of clinical copper deficiency.

PMID- 12785689
TI  - Hypophosphatemia associated with hypovitaminosis-D in Speke's gazelles (Gazella
      spekei).
AB  - Two juvenile male Speke's gazelles (Gazella spekei) at the St. Louis Zoo showed
      poor body condition, slowed growth, hunched stance, rough hair coat, and profound
      hypophosphatemia. The first gazelle was treated with parenteral phosphorous
      supplements but continued to deteriorate clinically and was euthanatized. The
      second gazelle had serum 25-hydroxyvitamin D levels of 0 nmol/L and was treated
      with i.m. injections of vitamin D. It died shortly after starting therapy. The
      only significant necropsy finding was multiple rib fractures in various stages of
      healing. Hypovitaminosis D has been confirmed in multiple Speke's gazelles in
      this collection, indicating possible deficiencies in the diet or in the amount of
      ultraviolet light available to the gazelles.

PMID- 12785690
TI  - Cholangiocarcinoma with metastasis in a captive Adelie penguin (Pygoscelis
      adeliae).
AB  - A captive male Adelie penguin (Pygoscelis adeliae), wild caught in 1976, died
      unexpectedly. Necropsy revealed cholangiocarcinoma with metastases to lung,
      pancreas, mesentery, and cloaca, the first known case of a penguin hepatic tumor.

PMID- 12785691
TI  - Multiple bilateral fractures of the lumbar transverse processes in a roe deer
      (Capreolus capreolus).
AB  - Multiple bilateral fractures of the lumbar transverse processes were
      radiographically identified postmortem in a recently captured roe deer (Capreolus
      capreolus). These fractures were probably caused by an avulsion of the psoas
      major occurring during introduction into the transport box. The deer probably
      died from shock caused by the fractures, muscle damage, and subsequent
      hemorrhage. Although easily overlooked, fractured lumbar transverse processes may
      indicate inadequate postcapture management practices.

PMID- 12785692
TI  - Imidacloprid treatment of marsupials for fleas (Pygiopsylla hoplia).
AB  - Two eastern barred bandicoots (Perameles gunnii), two eastern quells (Dasyunrus
      viverrinus), four fat-tailed dunnarts (Sminthopsis crassicaudata), a Leadbeater's
      possum (Gymnobelideus leadbeateri), a yellow-bellied glider (Petaurus australis),
      and a ring-tailed possum (Pseudocheirus peregrinus) were treated with
      imidacloprid (10.7 +/- 0.6 mg/kg topically, minimum dose 0.5 mg) after
      observation of fleas (Pygiopsylla hoplia) on animals and in their nest boxes. No
      live fleas or adverse reactions to imidacloprid were observed for 27 days
      following treatment. The ease of application, absence of toxicity, and long
      residual effect makes imidacloprid a useful drug for treating flea infestations
      in these marsupials.

PMID- 12785693
TI  - Chronic otitis externa/media with total ear canal ablation and bulla curettage in
      a North American bison (Bison bison).
AB  - An adult female North American bison (Bison bison) with a chronic otitis
      externa/media of the right ear was examined because of a 4-mo history of
      intermittent anorexia, apparent painful behavior, and auricular discharge from
      the right ear. Computerized tomography (CT) demonstrated osteolysis of the
      tympanic, petrous, and squamous aspects of the temporal bone with soft tissue
      replacement and sclerosis of the right bulla. A total ear canal ablation with
      bulla curettage was performed, and cefazolin-impregnated polymethacrylate beads
      were left within the right bulla and the remnant temporal bone. Six months after
      the surgery, the bison had no clinical signs of otitis media.

PMID- 12785694
TI  - Clinical challenge. Lung; multiple larval cestode cysts containg protoscoleces,
      consistent with the metacestode stage of Echinococcus granulosus.

PMID- 12785695
TI  - Restoration of reproductive potential following expiration or removal of
      melengestrol acetate contraceptive implants in golden lion tamarins
      (Leontopithecus rosalia).
AB  - Although reversible contraception is important to successful management of small
      populations, there are concerns about the reversibility of melengestrol acetate
      (MGA), the most commonly used implant in captive animals. Female golden lion
      tamarins (Leontopithecus rosalia) placed in potential breeding situations after
      surgical MGA implant removal showed a 75% return to reproduction within 2 yr,
      unlike golden-headed tamarins (Leontopithecus chrysomelas), which have had a 29%
      return to reproduction following implant removal. This rate was indistinguishable
      from the breeding probability for newly formed pairs involving nonimplanted
      females. Litter size, stillbirth rate, and infant survival rate were not
      significantly different between nonimplanted and implant-removed female golden
      lion tamarins. However, females with implants left in (and assumed to have
      expired) showed higher stillbirth and infant mortality rates than did females
      with implants removed. For seven female golden lion tamarins for which
      reproductive histories before and after MGA implantation were available, litter
      size was unaffected by MGA implantation and subsequent removal. Infant survival
      rate for these females appeared to be lower after removal but was
      indistinguishable from rates in the nonimplanted females. Prior reproductive
      experience, length of time with an implant, and age of the females did not affect
      the probability of breeding for females after removal of the implants. Overall,
      breeding probability of nonimplanted females declined with age. Although the
      results of this study confirm the reversibility of MGA implants in golden lion
      tamarins, there appear to be some effects on viability of offspring, particularly
      offspring born to females with implants left in and presumed expired.

PMID- 12785696
TI  - Electrophoretic patterns and immunoglobulin G levels in mouflon (Ovis orientalis
      musimon) and roe deer (Capreolus capreolus).
AB  - Serum protein and immunoglobulin G (IgG) levels were measured from 16 healthy
      mouflons (Ovis orientalis musimon) and from 28 roe deer (Capreolus capreolus) in
      French and Catalonian populations. Electrophoretic patterns were described for
      each species. The only significant gender-related difference was increased beta
      globulins in French roe deer males. Significantly increased alpha1-globulin
      levels and decreased IgG levels occurred in the young Catalonian roe deer
      compared with adults from the same group. Values for total proteins, beta
      globulins, gamma-globulin, and IgG were significantly higher in the French roe
      deer, while albumin and albumin/globulin ratio were higher in the Catalonian roe
      deer. Both populations had the same relative migration distances of the various
      protein fractions of the electrophoresis.

PMID- 12785697
TI  - Disposition of sulfadimethoxine in camels (Camelus dromedarius) following single
      intravenous and oral doses.
AB  - Single-dose pharmacokinetics of sulfadimethoxine were determined in six adult
      camels (Camelus dromedarius) following administration of a mean dosage of 17.5 +/
      2.7 mg/kg both i.v. and p.o. Serial blood samples were collected through an
      indwelling jugular catheter intermittently for 5 days for both routes.
      Sulfadimethoxine was assayed using high-performance liquid chromatography. Serum
      drug concentration versus time data for each animal was subjected to linear
      regression, with the best-fit model selected based on residual analysis. The data
      fit best into a two-compartment open model, with first-order input for oral
      administration. For orally administered drug, mean maximum serum concentration of
      19.3 +/- 1.7 microg/ml was reached at 11.41 +/- 2.59 hr, with an elimination rate
      constant of 0.09/hr +/- 0.05/hr and an elimination half-life of 11.7 +/- 3 hr.
      Mean peak serum concentration following i.v. administration was 223 +/- 48
      microg/ml. Mean volume of distribution at steady state was 0.393 +/- 0.049 L/kg.
      Elimination rate constants differed with i.v. and oral administration, suggesting
      a flip-flop model. Oral bioavailability was 103% +/- 38%. Comparison of maximum
      serum concentrations to the microbial breakpoint concentration reported for
      sulfadimethoxine (512 microg/ml) suggests that the dose used in this study, 17.5
      +/- 2.7 mg/kg, is insufficient for achieving therapeutic serum levels.

PMID- 12785698
TI  - Altered in vitro immune responses in green turtles (Chelonia mydas) with
      fibropapillomatosis.
AB  - The immune competence of green sea turtles (Chelonia mydas) with
      fibropapillomatosis was assessed using in vitro techniques to measure lymphocyte
      proliferation in response to mitogens. In comparison with captive, healthy green
      sea turtles, those afflicted with fibropapillomas demonstrated diminished
      proliferation with Concanavalin A, phytohemagglutinin (T-cell mitogens), and
      lipopolysaccharide (B-cell mitogen). Also, markedly decreased proliferative
      responses to the lymphocyte polyclonal stimulator combination of ionomycin and
      phorbol myristate acetate were observed. Total circulating white blood cell
      counts were not statistically different between the two groups, although an
      overall decrease in lymphocyte number was observed in the papilloma group. The
      albumin/globulin ratio was decreased in the papilloma group because of decreased
      albumin and increased gamma globulins.

PMID- 12785699
TI  - Electrocardiographic parameters of free-ranging roe deer (Capreolus capreolus).
AB  - Electrocardiographic parameters were measured in 28 free-ranging roe deer
      (Capreolus capreolus). The electrocardiograms (ECGs) were recorded in base-apex
      lead, standard bipolar limb leads (I, II, III), and augmented unipolar limb leads
      (aVR, aVL, aVF). Morphology and amplitude of P waves, QRS complexes, and T waves
      were analyzed in all seven leads. Cardiac rhythm, heart rate, and durations of P,
      QRS, and T waves, PR interval, QTc interval, and ST segment were calculated in
      the base-apex lead. The mean electrical axis for each individual was determined
      from the net amplitude of the QRS complex in leads I and II. All of the animals
      had a sinus rhythm. Heart rates ranged from 60-180 beats per minute, with a mean
      +/- SD of 104.8 +/- 44.1. The electrical axis was 100 degrees-220 degrees, with a
      mean +/- SD of 169.5 degrees +/- 40.8 degrees. The base-apex lead provided the
      most uniform ECG patterns and higher mean amplitudes than did standard leads.

PMID- 12785700
TI  - Psittacine paranasal sinus--a new definition of compartments.
AB  - Documentation of the psittacine paranasal sinuses has been limited. To provide
      more published detail, spiral computed tomography (CT) was used to scan the
      cephalic and cervical region from cadavers of 10 psittacine birds (Ara ararauna,
      Ara chloroptera, Ara macao, and Anodorhynchus hyacinthinus). Skeletal studies,
      histologic examinations, and evaluation of deep-frozen sections and anatomic
      preparations confirmed the results of the CT scans. New morphologic details of
      the paranasal sinus and some compartments were discovered. The paranasal sinuses
      of these macaws consist of two unpaired rostral compartments, followed caudally
      by eight paired compartments. Histologic examinations revealed that the walls of
      the paranasal sinuses consist of flat or cubic monolayer epithelium with
      underlying connective tissue. The described method of CT examination of these
      macaws, especially the positioning, scan orientation and parameters, and
      documentation of the normal paranasal sinus, provides a basis for future clinical
      use of CT.

PMID- 12785701
TI  - Chronic tubulointerstitial nephropathy in six okapis (Okapia johnstoni).
AB  - Renal tubular atrophy with conical and medullary interstitial fibrosis with
      severe thickening of the basement membranes of atrophic tubules was found in six
      okapis (Okapia johnstoni). Focal glomerular atrophy, probably secondary to
      ischemic collapse of the glomerular capillary tuft, was also observed. Although
      the etiologies and pathogeneses of these nephropathies are unclear, primary
      damage of the tubular epithelium appears to be the most likely cause, and
      toxicity from ingested plant material, possibly willow (Salix sp.), is a
      possibility.

PMID- 12785702
TI  - Diagnosis and surgical treatment of thyroid adenoma-induced hyperthyroidism in a
      green iguana (Iguana iguana).
AB  - An adult female green iguana (Iguana iguana) presented with polyphagia, loss of
      the dorsal spines, hyperactivity, increased aggression, tachycardia, and a
      bilobate mass palpable anterior to the thoracic inlet. Diagnosis of
      hyperthyroidism was based on a total T4 (30.0 nmol/L) elevated above that of
      clinically healthy iguanas (3.81 +/- 0.84 nmol/L), and histopathology confirmed a
      functional thyroid adenoma. Surgical thyroidectomy safely returned the lizard to
      a euthyroid state.

PMID- 12785703
TI  - Leptospira infection in two black rhinoceroses (Diceros bicornis michaeli).
AB  - Two black rhinoceroses (Diceros bicornis michaeli) developed clinical
      leptospirosis without hemolytic crises. The first rhinoceros presented with
      peracute depression, anorexia, rear leg trembling, dysuria, glucosuria,
      gastrointestinal discomfort, and decreased fecal output and died within 12 hr.
      Necropsy and histopathology revealed lesions within multiple organs.
      Leptospirosis was diagnosed postmortem based on positive fluorescent antibody
      staining of liver. The second rhinoceros presented 2 mo later with similar signs.
      It survived with treatment and was diagnosed with leptospirosis based on serology
      using microscopic agglutination testing and detection of urinary antigen using a
      fluorescent antibody technique. Leptospira kirschneri serovar grippotyphosa was
      postulated as the etiologic agent, with transmission probably occurring through
      wallow contamination by wild raccoons (Procyon lotor).

PMID- 12785704
TI  - Type I external skeletal fixation of radial fractures in microchiropterans.
AB  - An adult male big brown bat (Eptesicus fuscus) and an adult female hoary bat
      (Lasiurus cinereus) were presented with open transverse middiaphyseal left radial
      fractures. Initial repair was attempted by intramedullary pinning. When the
      fractures did not heal, intramedullary pins were removed and type I external
      skeletal fixators were placed. The fractures healed, and the big brown bat
      regained normal flight but the hoary bat did not.

PMID- 12785705
TI  - Brown bear (Ursus arctos arctos) femoral head and neck excision.
AB  - A 30-yr-old untamed European female brown bear (Ursus arctos arctos) with a
      craniodorsal luxation of the right femoral head and bilateral degenerative joint
      disease of the coxofemoral joint had a femoral head and neck excision following
      unsatisfactory conservative medical therapy. The bear was injected with zolazepam
      tiletamine, and anesthesia was induced with i.v. thiopental and maintained with
      isoflurane in oxygen via endotracheal tube. A lumbosacral epidural injection of
      medetomidine-bupivacaine provided additional analgesia. Slight initial
      cardiorespiratory depression was counteracted with fluid and inotropic drug
      administration and ventilatory assistance. The bear's gluteal muscle anatomy
      differs from that of the dog. Recovery was uneventful. The bear was confined
      indoors for 6 wk and was able to ambulate normally within 6 mo.

PMID- 12785706
TI  - Fatal pentastomiasis in captive African dwarf crocodile hatchlings (Osteolaemus
      tetraspis).
AB  - Six eggs from a captive African dwarf crocodile (Osteolaemus tetraspis) nest were
      artificially incubated. Two abnormal hatchlings with incomplete absorption of
      their yolk sacs died within 48 hr of hatching. No parasites were detected grossly
      or histologically in either hatchling. The remaining four apparently healthy
      hatchlings died without clinical signs at 3 wk of age, 1 wk after being fed live
      wild-caught fish and commercially raised goldfish. Necropsy revealed multiple
      white small wormlike organisms within the lungs, liver, and gastrointestinal
      tract of all four hatchlings. Histopathologic cross sections suggested that
      pentastomiasis was the cause of death, and whole parasites were identified as
      Sebekia mississippiensis. This infection was probably contracted by ingestion of
      live fish intermediate hosts infected with nymphal parasites. Avoiding the use of
      infected live fish or untreated fish products can prevent mortality of hatchling
      crocodilians caused by S. mississippiensis within zoological collections.

PMID- 12785707
TI  - Surgical resolution of an ectopic pregnancy in a captive gerenuk (Litocranius
      walleri walleri).
AB  - A full-term ectopic pregnancy was diagnosed in a multiparous, captive gerenuk
      (Litocranius walleri walleri) following prolonged gestation without parturition.
      Until 213 days of gestation, fetal viability was determined by transabdominal
      ultrasound of fetal heartbeat, physical palpation, and visual observations of
      fetal movements. Survey abdominal radiographs obtained at day 229 of gestation
      revealed a fully mineralized fetal skeleton in an inappropriate position for
      parturition. Surgical exploration revealed a full-term, nonviable, male calf
      contained within fetal membranes attached to the omentum. Histologic examination
      of the fetal membranes identified lesions compatible with placenta-cotyledon
      separation occurring prior to surgical removal. No congenital fetal abnormalities
      or infectious processes were identified. Visual observation of the reproductive
      tract at the time of surgery revealed no abnormalities or evidence of concurrent
      pregnancy.

PMID- 12785708
TI  - Rectal prolapse in a free-ranging mountain gorilla (Gorilla beringei beringei):
      clinical presentation and surgical management.
AB  - A juvenile female mountain gorilla (Gorilla beringei beringei) of the Mubare
      tourist group in Bwindi Impenetrable National Park, Uganda, developed a severe,
      complete rectal prolapse that did not spontaneously resolve. Eight months prior,
      a juvenile female mountain gorilla of the Mubare group developed a mild, complete
      rectal prolapse that resolved spontaneously within 24 hr. Field guides reported
      that spontaneously resolving prolapses had been seen previously in two other
      juveniles, one of which was from the Mubare group. The tissue became increasingly
      necrotic and maggot infested over the course of 1 wk. Surgical intervention
      involved amputation of the affected rectal tissues and suturing the viable
      portion to the anal sphincter muscle with simple interrupted absorbable sutures.
      The surgery was performed in the field in accordance with Uganda Wildlife
      Authority policies. Antibiotics and anthelmintics were administered systemically,
      and the gorilla returned to the group. The gorilla appeared to recover fully
      after 3 wk. Histology of the resected rectal tissue confirmed intense
      inflammation and necrosis with myiasis but did not reveal an underlying etiology.

PMID- 12785709
TI  - Occurrence of Listeria spp. in captive antelope herds and their environment.
AB  - Two juvenile scimitar-horned oryx (Oryx dammah) at the Wild Animal Park
      Planckendael died from acute septicemia caused by Listeria monocytogenes serovar
      4b. Subsequently, Listeria spp. were isolated from the feces, food, and
      environment of seven antelope species and examined using a two-stage enrichment
      procedure in Fraser Broth, followed by isolation on PALCAM agar. A total of
      40/170 samples (23.5%) was positive for Listeria spp. No organisms were cultured
      in 83/170 samples (48.8%), and 47 samples (27.6%) were overgrown with Bacillus
      spp. Nonpathogenic Listeria spp. were isolated from 16/70 fecal samples, 22/40
      soil samples, and 2/60 feed samples. Listeria monocytogenes serovar 1/2b was
      isolated from two soil samples collected in the enclosure of the scimitar-horned
      oryx.

PMID- 12785710
TI  - A simple method of providing intermittent positive-pressure ventilation to
      etorphine-immobilized elephants (Loxodonta africana) in the field.
AB  - Five African elephants (Loxodonta africana) were immobilized with etorphine in
      Waza National Park, Cameroon, for the purpose of deploying radio/satellite
      tracking collars. A portable ventilator constructed from two high-flow demand
      valves and the Y-piece of a large animal anesthesia circuit was used to provide
      intermittent positive-pressure ventilation with 100% oxygen. Oxygenation status
      improved dramatically in all five elephants. In one hypoxemic elephant, arterial
      PaO2 increased from 40 to 366 mm Hg. The results of this study demonstrate that
      both oxygenation and ventilation can be readily controlled in etorphine
      immobilized elephants even under remote field conditions.

PMID- 12785711
TI  - Presence of encysted immature nematodes in a released whooping crane (Grus
      americana).
AB  - Numerous nematode cysts were observed throughout the mesentery and on the surface
      of gastrointestinal organs in a whooping crane (Grus americana) that was found
      dead in a central Florida marsh. Morphology of the excysted nematodes most
      closely resembled third-stage larvae in the order Spirurida but were not similar
      to any species previously reported in whooping cranes. Evidence presented
      suggests that the larvae may be Physocephalus sexalatus, a swine spirurid in the
      subfamily Ascaropsinae that is commonly found encapsulated in birds, amphibians,
      and reptiles. We suspect that the whooping crane may potentially serve as a
      transport host for this parasite.

PMID- 12785712
TI  - Clinical challenge. Bone-density foreign body in the interdigital space between
      digits III and IV.

PMID- 12785713
TI  - What's new in translation initiation? The first translation determines the fate
      of mRNA.
AB  - The two terms 'translation' and 'protein synthesis' are interchangeable in
      describing the process whereby the genetic code in the form of messenger RNA
      (mRNA) is deciphered such that amino acids cognate with the triplet code are
      joined end to end to form a peptide chain. However, new data suggest that the
      initial act of translation on newly synthesised mRNA also functions to proofread
      mRNA for errors. Aberrant mRNAs detected in this way are rapidly degraded before
      their encoded proteins impede normal cell function. Initiation of surveillance
      translation appears to differ from that of regular protein synthesis in three
      ways: (i) composition of the substrate; (ii) temporal and spatial restrictions;
      (iii) factors used to recruit the ribosome. This review discusses translational
      aspects of mRNA surveillance, primarily in the context of the mammalian system,
      although much information has come from studies in yeast and other organisms.

PMID- 12785714
TI  - Molecular adaptations to cold in psychrophilic enzymes.
AB  - Psychrophiles or cold-loving organisms successfully colonize cold environments of
      the Earth's biosphere. To cope with the reduction of chemical reaction rates
      induced by low temperatures, these organisms synthesize enzymes characterized by
      a high catalytic activity at low temperatures associated, however, with low
      thermal stability. Thanks to recent advances provided by X-ray crystallography,
      protein engineering and biophysical studies, we are beginning to understand the
      molecular adaptations responsible for these properties which appear to be
      relatively diverse. The emerging picture suggests that psychrophilic enzymes
      utilize an improved flexibility of the structures involved in the catalytic
      cycle, whereas other protein regions if not implicated in catalysis may or may
      not be subjected to genetic drift.

PMID- 12785715
TI  - Toward an understanding of cell growth and the cell division cycle of unicellular
      photoautotrophic cyanobacteria.
AB  - The cell division cycle of Synechococcus sp. strain PCC 6301 in light is
      characterized by the sequential and orderly appearance of macromolecular
      synthesis periods. In the dark, macromolecular synthesis and cell division are
      severely curtailed. When dark-incubated cultures are reexposed to light, a new
      cell cycle is initiated. The pattern of the cell events displayed by
      Synechococcus in light and the absence of sustained growth in dark incubation
      conditions suggests that light-activated regulatory molecules control
      macromolecular synthesis and the cell division cycle. For example, ribosomal RNA
      synthesis is stimulated by a light-activated DNA binding factor in light but not
      in the dark. Light/dark conditions induce cell synchrony in Prochlorococcus.
      Distinct G1, S and G2 phases characterize cell cycles of marine Synechococcus and
      Prochlorococcus. Cell division in Synechococcus elongatus PCC 7942 and marine
      Synechococcus is controlled by circadian oscillators.

PMID- 12785716
TI  - Relaxin: a pregnancy hormone as central player of body fluid and circulation
      homeostasis.
AB  - The peptide relaxin has long been regarded as an important hormone of pregnancy,
      contributing to changes in connective tissue composition as well as to regulation
      of implantation, myometrial activity and labor. On the other hand, the
      astonishing pleiotropy of this hormone escaped scientific awareness. This review
      focuses on new facets of relaxin, including its antifibrotic effects, its role in
      the control of pituitary hormone release, its vasodilator and pro-angiogenic
      properties and its versatile myocardial actions. Recent progress in understanding
      relaxin's receptor and signaling mechanisms is also highlighted. The peptide will
      be characterized as potential regulator of body fluid and circulation
      homeostasis.

PMID- 12785717
TI  - The emerging role for sphingolipids in the eukaryotic heat shock response.
AB  - Eukaryotic cells have a highly conserved response to an increase in temperature,
      termed the heat shock response. Recent research has revealed multiple roles for
      various sphingolipids in the heat shock responses of both yeast and mammalian
      cells. Heat stressed or shocked yeast and mammalian cells have an acute
      activation of serine palmitoyltransferase, resulting in the de novo biosynthesis
      of sphingolipids. Also, both mammalian and yeast cells were shown to increase
      ceramide levels upon heat stress or shock. In yeast cells, several functions have
      emerged for the de novo produced sphingoid bases in terms of the heat stress
      response. These functions include a role in accumulation of trehalose, a role in
      the heat-induced transient G0/G1 cell cycle arrest and phytosphingosine
      activation of a ubiquitin protein degradation pathway. However, in mammalian
      systems, ceramides have been demonstrated as bioactive lipids. Ceramides produced
      in response to heat shock were demonstrated to induce the production of c-jun,
      leading to apoptosis, and to be upstream of dephosphorylation of serine-rich
      proteins. Increasingly, sphingolipids are emerging as bioactive signaling
      molecules involved in numerous aspects of the eukaryotic heat shock response.

PMID- 12785718
TI  - Cathelicidins--a family of multifunctional antimicrobial peptides.
AB  - One component of host defence at mucosal surfaces are epithelial-derived
      antimicrobial peptides. Cathelicidins are one family of antimicrobial peptides
      characterized by conserved pro-peptide sequences that have been identified in
      several mammalian species. LL-37/hCAP-18 is the only cathelicidin found in humans
      and is expressed in inflammatory and epithelial cells. Besides their direct
      antimicrobial function, cathelicidins have multiple roles as mediators of
      inflammation influencing diverse processes such as cell proliferation and
      migration, immune modulation, wound healing, angiogenesis and the release of
      cytokines and histamine. Finally, cathelicidin antimicrobial peptides qualify as
      prototypes of innovative drugs that may be used to treat infection and/or
      modulate the immune response. This review provides an overview of antimicrobial
      peptides of the cathelicidin family, the structures of their genes and peptides
      and their biological functions.

PMID- 12785719
TI  - Transcriptional repression in eukaryotes: repressors and repression mechanisms.
AB  - For many, if not most genes, the initiation of transcription is the principle
      point at which their expression is regulated. Transcription factors, some of
      which bind to specific DNA sequences, generally either activate or repress
      promoter activity and thereby control transcription initiation. Recent work has
      revealed in molecular detail some of the mechanisms used by transcription factors
      to bring about transcriptional repression. Some transcriptional repressor
      proteins counteract the activity of positively acting transcription factors.
      Other repressors inhibit the basal transcription machinery. In addition, the
      repression of transcription is often intimately associated with chromatin re
      organisation. Many transcriptional repressor proteins interact either directly or
      indirectly with proteins that remodel chromatin or can themselves influence
      chromatin structure. This review discusses the mechanisms by which
      transcriptional repression is achieved and the role that chromatin re
      organisation plays in this process.

PMID- 12785720
TI  - Cellular and molecular action of the putative GABA-mimetic, gabapentin.
AB  - Gabapentin was originally designed as an anti-convulsant gamma-aminobutyric acid
      (GABA) mimetic capable of crossing the blood-brain barrier. In the present review
      we show that although gabapentin is not a GABA mimetic, it has great utility as
      an add-on therapy for epilepsy and as a first-line treatment for neuropathic
      pain. We summarise the studies that have been performed which demonstrate that
      gabapentin appears to interact with a novel binding site expressed at high
      density within the central nervous system (CNS), namely the alpha2delta voltage
      dependent calcium channel subunit. The review continues by examining the effects
      of gabapentin on calcium channel function and neurotransmitter release before, in
      the latter part of the review, summarising the more recently discovered actions
      of gabapentin in relation to intracellular signalling.

PMID- 12785722
TI  - Mast cells stimulated by membrane-bound, but not soluble, steel factor are
      dependent on phospholipase C activation.
AB  - The steel factor (SLF) and c-Kit growth factor/receptor pair are key molecules
      governing mast cell development and survival. SLF is expressed on stromal cells
      as a membrane-bound molecule (mSLF) which can be cleaved by proteases to release
      a soluble form (sSLF). We investigated the importance of phospholipase C (PLC)
      activation in mast cells stimulated by sSLF and mSLF. PLC antagonists U73122,
      neomycin sulfate and oleic acid inhibited mast cell thymidine incorporation
      stimulated by mSLF, but not by sSLF. These antagonists suppressed sSLF-induced
      Ca2+ transients but did not significantly interfere with c-Kit phosphorylation or
      PLC-gamma2 recruitment. p85, the regulatory subunit of phosphatidylinositol 3
      kinase (PI3-kinase), was found to be efficiently recruited to c-Kit following
      stimulation by sSLF or mSLF. However PKB/Akt, a kinase activated by PI3-kinase
      products, was phosphorylated following sSLF stimulation, but not with mSLF. Taken
      together, these studies demonstrate the importance of PLC activation by mSLF in
      supporting mast cells.

PMID- 12785721
TI  - The expression of Sam68, a protein involved in insulin signal transduction, is
      enhanced by insulin stimulation.
AB  - The role of Sam68, an RNA binding protein and putative substrate of the insulin
      receptor (IR) in insulin signaling was studied using CHO wild type (WT) cells,
      CHO cells overexpressing IR, and rat white adipocytes as a physiological system.
      In CHO-IR cells and adipocytes, Sam68 was tyrosine phosphorylated in response to
      insulin, and then associated with p85 phosphatidylinositol-3 kinase along with
      IRS-1. Sam68 was localized mainly in the nucleus of CHO-WT, and both in the
      nucleus and cytoplasm of CHO-IR cells, but only in the cytoplasm of rat white
      adipocytes. Insulin stimulation for 16 h enhanced the expression of Sam68 in rat
      adipocytes and CHO-IR cells. Moreover, CHO-IR cells expressed more Sam68 than CHO
      WT, suggesting that overexpression of the IR is enough to induce the expression
      of Sam68. In summary, these results demonstrate that Sam68 works as a cytoplasmic
      docking protein which is recruited by IR signaling and whose expression is
      induced by insulin stimulation, suggesting a putative role for Sam68 in insulin
      signal transduction.

PMID- 12785723
TI  - Myocardial function and energy metabolism in carnitine-deficient rats.
AB  - Carnitine is essential for mitochondrial metabolism of long-chain fatty acids and
      thus for myocardial energy production. Accordingly, carnitine deficiency can be
      associated with cardiomyopathy. To better understand this disease, we determined
      myocardial function and energy metabolism in a rat model of carnitine deficiency.
      Carnitine deficiency was induced by a 3- or 6-week diet containing N-trimethyl
      hydrazine-3-propionate, reducing cardiac and plasma carnitine by 70-85%.
      Myocardial function was investigated in isolated isovolumic heart preparations.
      Carnitine-deficient hearts showed left ventricular systolic dysfunction, reduced
      contractile reserve, and a blunted frequency-force relationship independently of
      the substrate used (glucose or palmitate). After glycogen depletion, palmitate
      could not sustain myocardial function. Histology and activities of carnitine
      palmitoyl transferase, citrate synthase, and cytochrome c oxidase were unaltered.
      Thus, as little as 3-6 weeks of systemic carnitine deficiency can lead to
      abnormalities in myocardial function. These abnormalities are masked by
      endogenous glycogen and are not accompanied by structural alterations of the
      myocardium or by altered activities of important mitochondrial enzymes.

PMID- 12785724
TI  - Sphingosine 1-phosphate antagonizes human neutrophil apoptosis via p38 mitogen
      activated protein kinase.
AB  - Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis,
      although its role in neutrophil apoptosis remains poorly investigated. Here, we
      show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in
      neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis
      inhibiting capacity of SPP. Consequently, we investigated the involvement of
      potential modulators of apoptosis that are activated downstream of Gi/G0-coupled
      receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal
      kinases was detected during apoptosis or after adding SPP. In contrast, there was
      a transient decrease in phosphorylation of both extracellular-regulated kinase
      (ERK) and p38 mitogen-activated protein kinase (MAPK) during both spontaneous and
      anti-Fas-induced apoptosis. Although exogenous SPP reversed these reductions in
      kinase activity, experiments with inhibitors of ERK (PD98059) and p38 MAPK
      (SB203580) revealed that only SB203580 counteracted the effect of SPP. Thus, SPP
      counteracts neutrophil apoptosis via a Gi/G0 protein survival-signalling pathway
      that includes modulation of p38 MAPK activity.

PMID- 12785725
TI  - The purine nucleoside cycle in cell-free extracts of rat brain: evidence for the
      occurrence of an inosine and a guanosine cycle with distinct metabolic roles.
AB  - The purine nucleoside cycle is a cyclic pathway composed of three cytosolic
      enzymes, hypoxanthine-guanine phosphoribosyltransferase, IMP-GMP specific 5'
      nucleotidase, and purine-nucleoside phosphorylase. It may be considered a 'futile
      cycle', whose net reaction is the hydrolysis of 5-phosphoribosyl-1-pyrophosphate
      to inorganic pyrophosphate and ribose 1-phosphate. The availability of a highly
      purified preparation of cytosolic 5'-nucleotidase prompted us to reconstitute the
      purine nucleoside cycle. Its kinetics were strikingly similar to those observed
      when dialyzed extracts of rat brain were used. Thus, when the cycle is started by
      addition of inorganic phospate (Pi) and hypoxanthine or inosine (the 'inosine
      cycle'), steady-state levels of the intermediates are observed and the cycle
      'turns over' as far as 5-phosphoribosyl-1-pyrophosphate is being consumed. In the
      presence of ATP, which acts both as an activator of IMP-GMP-specific 5'
      nucleotidase and as substrate of nucleoside mono- and di-phosphokinases, no IDP
      and ITP are formed. The inosine cycle is further favored by the extremely low
      xanthine oxidase activity. Evidence is presented that ribose 1-phosphate needed
      to salvage pyrimidine bases in rat brain may arise, at least in part, from the 5
      phosphoribosyl-1-pyrophosphate hydrolysis as catalyzed by the inosine cycle,
      showing that it may function as a link between purine and pyrimidine salvage.
      When the cycle is started by addition of Pi and guanine (the 'guanosine cycle'),
      xanthine and xanthosine are formed, in addition to GMP and guanosine, showing
      that the guanosine cycle 'turns over' in conjunction with the recycling of ribose
      1-phosphate for nucleoside interconversion. In the presence of ATP, GDP and GTP
      are also formed, and the velocity of the cycle is drastically reduced, suggesting
      that it might metabolically modulate the salvage synthesis of guanyl nucleotides.

PMID- 12785726
TI  - SU5416 sensitizes ovarian cancer cells to cisplatin through inhibition of
      nucleotide excision repair.
AB  - SU5416 is reported to be a selective inhibitor of vascular endothelial growth
      factor, and it has metwith limited success in the clinic. In the present study,
      we investigated whether SU5416 could augment cisplatin-induced cytotoxicity in
      human ovarian cancer cells. When used as a single agent, 2-h exposures to SU5416
      were not harmful to the cells up to doses of 100 microM. For 48-h exposures, the
      SU5416 IC20 and IC50 were 17 and 34 microM, respectively. When used with
      cisplatin, the effect of SU5416 was sequence dependent. SU5416 given first was
      subadditive, whereas cisplatin given first was supraadditive. Cisplatin was given
      as a 1-h exposure. Augmented cisplatin cytotoxicity was seen with 2-h exposures
      to SU5416 at doses of 17-34 microM. This was associated with a decrease in
      cisplatin-DNA adduct repair, as measured by atomic absorbance spectrometry.
      Treatment of the ovarian carcinoma cells with SU5416 was also associated with a
      reduced expression of ERCC-1 protein and c-jun mRNA, as well as a decrease in c
      Jun and JNK activities. We conclude that SU5416 can be used to augment cisplatin
      induced cell killing at doses that are non-toxic. This effect may occur through
      direct or indirect reduction of the activity of AP-1 and DNA repair.

PMID- 12785727
TI  - The first non-LTR retrotransposon characterised in the cephalochordate amphioxus,
      BfCR1, shows similarities to CR1-like elements.
AB  - BfCR1 is the first non-long terminal repeat retrotransposon to be characterised
      in the amphioxus genome. Sequence alignment of the predicted translation product
      reveals that BfCR1 belongs to the CR1-like retroposon class, a family widely
      distributed in vertebrate and invertebrate lineages. Structural analysis shows
      conservation of the specific motifs of the ORF2-CR1 elements: the N-terminal
      endonuclease, the reverse transcriptase and the C-terminal domains. The BfCR1
      element possesses an atypical 3' terminus consisting of the tandem repeat (AAG)6.
      We gathered evidence supporting the mobility of this element and report an
      estimated 15 copies of BfCR1, mostly truncated, per haploid genome, a remarkably
      low number when compared to that of vertebrates. Phylogenetic analysis, including
      the amphioxus element, seems to indicate that (i) CR1-like retroposons cluster in
      a monophyletic group and (ii) the CR1-like family was already present in the
      chordate ancestor. Our data provide further support for the horizontal
      transmission of CR1-like elements during early vertebrate evolution.

PMID- 12785729
TI  - Synthesis and PGE2 inhibitory activity of 5,7-dihydroxyflavones and their O
      methylated flavone analogs.
AB  - 5,7-Dihydroxyflavones and their O-methylated flavone analogs were prepared and
      evaluated their anti-inflammatory activity to decipher the structure-activity
      relationships. Most of the analogs were achieved from 2,4,6
      trihydroxyacetophenone in 4 steps. 5,7-Dihydroxy-4'-methoxyflavone (4c) and 7
      hydroxy-4',5-dimethoxyflavone (6c) were prepared following a different synthetic
      pathway. Among the synthetic flavones tested, 5-hydroxy-7-methoxyflavone analogs
      (3a-3e) showed moderate inhibitory activities of PGE2 production from LPS-induced
      RAW 264.7 cells.

PMID- 12785728
TI  - Fenofibrate inhibits angiogenesis in vitro and in vivo.
AB  - Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator,
      used as a normolipidemic agent, is thought to offer additional beneficial effects
      in atherosclerosis. Since angiogenesis is involved in plaque progression,
      hemorrhage, and instability, the main causes of ischemic events, this study was
      designed to evaluate the action of fenofibrate on angiogenesis. Our results show
      that fenofibrate (i) inhibits endothelial cell proliferation induced by
      angiogenic factors, followed at high concentrations by an increase in apoptosis,
      (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits
      capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo.
      Concerning the mechanism of action, the inhibition of endothelial cell migration
      by fenofibrate can be explained by a disorganization of the actin cytoskeleton.
      At the molecular level, fenofibrate markedly decreased basic fibroblast growth
      factor-induced Akt activation and cyclooxygenase 2 gene expression. This
      inhibition of angiogenesis could participate in the beneficial effect of
      fenofibrate in atherosclerosis.

PMID- 12785730
TI  - Synthesis of allylthiopyridazine derivatives and inhibition of aflatoxin B1
      induced hepatotoxicity in rats.
AB  - Five kinds of allylthiopyridazine derivatives were synthesized and their
      chemoprotective activities examined in rats exposed to aflatoxin B1-toxicant.
      Rats were pretreated with five allylthiopyridazine derivatives at daily oral
      doses of 50 mg/kg for 10 consecutive days, and during this period with one or
      three repeated doses of the potent hepatotoxin, aflatoxin B1. The
      hepatoprotective effects of the allylthiopyridazine derivatives against aflatoxin
      B1 (1 mg/kg, three times at intervals of 3 days, i.p., or at 3 mg/kg, once at
      final days, i.p.) administration were showed the significantly normal as compared
      with control in body and liver weights. Aspartate aminotransferase and alanine
      aminotransferase levels were markedly elevated after aflatoxin B1 administration,
      and pretreatment with allylthiopyridazine derivatives, before aflatoxin B1
      administration, resulted in decreased levels of these enzymes. In addition, the
      allylthiopyridazine derivatives, K6 (3-methoxy-), K8 (3-chloro-), K16 (3-ethoxy-)
      and K17 (3-n-propoxy), induced elevated hepatic GSH levels. Four kinds of
      allylthiopyridazine derivatives investigated were effective against aflatoxin B1
      induced hepatotoxicity.

PMID- 12785731
TI  - Synthesis of new uracil-5-sulfonamide derivatives and immunostimulatory effect of
      a chemically modified hemolymph of Biomphalaria alexandrina on Schistosoma
      mansoni infected mice.
AB  - Some N-p-substituted phenyl uracil-5-sulphonamide derivatives have been
      synthesized to be evaluated as molluscicides against Biomphalanaria alexandrina
      snails, the intermediate host of Schistosoma mansoni. Schistosoma mansoni
      infected mice were treated with hemolymph obtained from pre-treated Biomphalana
      alexandrina snails with the products 4a, 10a, 10b and 4b or obtained from non
      treated snails. The selection of the concentration based on the predetermined
      dose which caused mortality of less than 50% of snails/24 h. LC50 of compounds
      4a, 10a, 10b and 4b was 50, 100, 200 and 50 ppm respectively. The result showed
      that immunostimulatory effect of treated hemolymph with compounds 4a, 10a and 4b
      was related to significant protective effects (44.4, 34.6 and 50.4% reduction in
      worm burden respectively). In addition, mean total worm burdens were
      significantly reduced in non treated hemolymph by 33.8%. The effect of hemolymph
      obtained from treated or non treated snails on S. mansoni adult worms antigens
      was studied by indirect immunofluorescence technique using chronic mouse sera
      (CMS). The results indicated that there was a strong reaction with epitopes in
      gut epithelium, tubercles, teigument and subtegumental musculature of untreated
      and treated S. mansoni adult worms antigens. Therefore, treatment of hemolymph
      obtained from pre-treated snails with compounds 4a, 10a, and 4b can stimulate
      specific immune response and induce protective effects against S. mansoni
      infection.

PMID- 12785732
TI  - Neuraminidase inhibitors from Reynoutria elliptica.
AB  - In the course of screening neuraminidase inhibitors from herbal medicines,
      Reynoutria elliptica exhibited high inhibitory activity. Four active compounds
      were isolated from the ethyl acetate soluble fraction by consecutive purification
      using sillica gel, Sephadex LH-20 chromatography, and recrystallization. The
      chemical structures of these compounds were identified as 1,3,8-trihydroxy-6
      methylanthraquinone (emodin) 1,8-dihydroxy-3-methoxy-6-methylanthraquinone
      (emodin 3-methyl ether; physcion), 1,3,8-trihydroxy-6-hydoxymethylanthraquinone
      (omega-hydroxyemodin), and 3,5,4'-trihydroxystilbene (trans-resvertrol) by
      spectral data including MS, 1H-, and 13C-NMR. The IC50 values of emodin, emodin 3
      methyl ether, omega-hydroxyemodin, and trans-resvertrol were 2.81, 74.07, 10.49,
      and 8.77 microM, respectively. They did not inhibit other glycosidase such as
      glucosidase, mannosidase, and galactosidase, indicating that they were relatively
      specific inhibitors of neuraminidase.

PMID- 12785733
TI  - Effect of ginsenoside Rd on nitric oxide system induced by lipopolysaccharide
      plus TNF-alpha in C6 rat glioma cells.
AB  - Effects of ginsenosides on nitric oxide (NO) production induced by
      lipopolysaccharide plus TNF-alpha (LNT) were examined in C6 rat glioma cells.
      Among several ginsenosides, ginsenoside Rd showed a complete inhibition against
      LNT-induced NO production. Ginsenoside Rd attenuated LNT-induced increased
      phosphorylation of ERK. Among several immediate early gene products, only Jun B
      and Fra-1 protein levels were increased by LNT, and ginsenoside Rd attenuated Jun
      B and Fra-1 protein levels induced by LNT. Furthermore, LNT increased AP-1 DNA
      binding activities, which were partially inhibited by ginsenoside Rd. Our results
      suggest that ginsenoside Rd exerts an inhibitory action against NO production via
      blocking phosphorylation of ERK, in turn, suppressing immediate early gene
      products such as Jun B and Fra-1 in C6 glioma cells.

PMID- 12785734
TI  - Inhibition of COX-2 activity and proinflammatory cytokines (TNF-alpha and IL
      1beta) production by water-soluble sub-fractionated parts from bee (Apis
      mellifera) venom.
AB  - Bee venom is used as a traditional medicine for treatment of arthritis. The anti
      inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from
      bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and
      pro-inflammatory cytokines (TNF-alpha and IL-1beta) production, in vitro. COX-2
      is involved in the production of prostaglandins that mediate pain and support the
      inflammatory process. The aqueous partition of bee venom showed strong dose
      dependent inhibitory effects on COX-2 activity (IC50 = 13.1 microg/mL), but did
      not inhibit COX-1 activity. The aqueous partition was subfractionated into three
      parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between
      10 KDa and 20 KDa) and B-F3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX
      2 activity and COX-2 mRNA expression in a dose-dependent manner, without
      revealing cytotoxic effects. TNF-alpha and IL-1beta, are potent pro-inflammatory
      cytokines and are early indicators of the inflammatory process. We also
      investigated the effects of three subfractions on TNF-alpha and IL-1beta
      production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3,
      inhibited TNF-alpha and IL-1beta production. These results suggest the
      pharmacological activities of bee venom on anti-inflammatory process include the
      inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines
      (TNF-alpha, and IL-1beta) production.

PMID- 12785735
TI  - Anti-Aspergillus activities of plant essential oils and their combination effects
      with ketoconazole or amphotericin B.
AB  - The essential oils from Cedrus atlantica, Styrax tonkinensis, Juniperus communis,
      Lavandula angustifolia, Melaleuca alternifolia, Pelargonium graveolens,
      Pogesternon patchouli and Rosmarinus officinalis were analyzed by GC-MS.
      Antifungal activities of the oils were investigated by disk diffusion assay and
      the broth dilution method against Aspergillus niger and A. flavus. The effects of
      geraniol and the essential oil fraction from P. graveolens on the antifungal
      activity of amphotericin B and ketoconazole were examined using a checkerboard
      microtiter assay against both Aspergillus fungi. Most of the tested essential
      oils, with the exception of C. atlantica, J. communis, and P. patchouli,
      significantly inhibited growth of A. niger and to a lesser extent that of A.
      flavus, with MICs (minimal inhibitory concentrations) in the range 0.78-12.5
      mg/mL. The essential oil fraction of P. graveolens and its main components,
      geraniol and citronellol, exhibited additive effects with amphotericin B and with
      ketoconazole against both Aspergillus species, resulting in fractional inhibitory
      concentration (FIC) indices ranging from 0.52 to 1.00.

PMID- 12785737
TI  - Effects of a naphthoquinone analog on tumor growth and apoptosis induction.
AB  - Vitamin K-related analogs induce growth inhibition in various cancer cell lines.
      A naphthoquinone analog, termed 2,3-dichloro-5, 8-dihydroxy-1,4-naphthoquinone
      (DDN), induces apoptosis in human promyeloid leukemic HL-60 cells, and shows
      antitumor activity in vivo. Following treatment with DDN, evidence of apoptosis,
      including DNA fragmentation and cleavage of poly ADP ribose polymerase (PARP),
      was observed. DDN induced an upregulation of proapoptotic Bax protein, and Bid
      cleavage. Antiapoptotic Bcl-2 protein levels were not changed by DDN, but the
      expression of Bcl-xL was decreased. In addition, DDN reduced the mass of solid
      tumor in the Sarcoma 180 tumor-bearing mouse model. These results indicate that
      DDN exerts antitumor activity, which appears to be related to the induction of
      apoptosis by regulating Bcl-2 family proteins.

PMID- 12785736
TI  - Effects of polycyclic aromatic hydrocarbons on liver and lung cytochrome P450s in
      mice.
AB  - Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce
      cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well
      known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene,
      chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of
      hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice
      were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3
      consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-O
      dealkylases were significantly and differentially induced in both liver and lung.
      Moreover, other CYP isozyme-associated monooxygenase activities were also induced
      significantly in liver and lung with characteristic induction profiles. Our
      present results suggest that individual PAHs might have inductive effects on CYP
      isozymes, and that the characteristic inductive effects of individual PAHs on
      certain CYP isozymes would be developed as a marker for determining exposure to
      certain PAHs.

PMID- 12785738
TI  - Tyrosine kinase is involved in hemin-induced pyresis.
AB  - To investigate the mechanisms involved in hemin-induced febrile response, the
      rectal temperature of rats were measured after intracerebroventricular (i.c.v.)
      injections of hemin, with or without antagonists. Hemin (10 microg) elicited a
      significant febrile response, which lasted from 30 min, to more than 6 h, after
      its administration, but this was not the case with biliverdin (i.c.v.) and
      bilirubin (i.c.v.). The hemin-induced febrile response was significantly
      inhibited by pretreatment with an inhibitor of tyrosine kinase (genistein), but
      not by pretreatment with an inhibitor of protein kinase C (chelerythrine) and a
      scavenger of iron (deferoxamine). These results suggest that tyrosine kinase is
      involved in the hemin-induced febrile response.

PMID- 12785739
TI  - Quantitative analysis of tiropramide in human blood by gas chromatography with
      nitrogen-phosphorus detector.
AB  - The analytical method of antispasmodic agent tiropramide ((+/-)alpha
      (benzoylamino)-4-[2-(diethylamino)ethoxy]-N,N-dipropylbenzenepropanamide
      hydrochloride) was developed by gas chromatography/nitrogen-phosphorus detector
      (GC/NPD) in human plasma. Two kinds of tiropramide tablets were orally
      administered to volunteers by Latin square crossover design, and blood was
      withdrawn as designed schedule. The plasma of 1 mL was loaded on Sep-pak C18
      cartridge and eluted with methanol after washing with 30% methanol. The residue
      dissolved in 100 microL of methanol after evaporation was analyzed by GC/NPD.
      Precision (CV%) of intra-day was located within 2.6% and accuracy was less than
      9.7%. Inter-day precision was below 8.7% and accuracy was relatively good as less
      than 14%. Plasma samples obtained from human volunteers were analyzed for the
      determination of tiropramide concentration by using this method. The method was
      sensitive, rapid and suitable enough to be applied for pharmacokinetic and
      bioequivalence studies of tiropramide in human volunteers.

PMID- 12785740
TI  - Enhanced ex vivo buccal transport of propranolol: evaluation of phospholipids as
      permeation enhancers.
AB  - The aim of the present study was to evaluate the effects of two phospholipid
      permeation enhancers, lysophosphatidylcholine (LPC) and
      didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative,
      sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of
      propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The
      permeation rate of [3H]PPL as measured by steady-state fluxes increased with
      increasing EtOH concentration. A significant flux enhancement (P<0.05) was
      achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation
      enhancer concentration, the buccal permeation of [3H]PPL was significantly
      enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the
      control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater
      degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with
      an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with
      2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no
      significant difference between LPC and DDPC for the flux values and apparent
      permeability coefficients of [3H]PPL. These results suggest that phospholipids
      are suitable as permeation enhancers for the buccal delivery of drugs.

PMID- 12785741
TI  - Microencapsulation of water-soluble isoflavone and physico-chemical property in
      milk.
AB  - This study was carried out to investigate the addition of water-soluble
      isoflavone into milk by means of microencapsulation technique. The yield of
      microencapsulation, sensory attributes, and capsule stability of water-soluble
      isoflavone microcapsules in milk were measured. Coating materials used was
      polyglycerol monostearate (PGMS), and core material was water-soluble isoflavone.
      The encapsulation yield of water-soluble isoflavone with PGMS was 67.2% when the
      ratio of coating material to core material was 15:1. The rate of water-soluble
      isoflavone release from capsules was 18, 19, and 25% when stored at 4, 20, and 30
      degrees C for 12 days in milk, respectively. In sensory evaluation, beany flavor
      and color of microencapsuled water-soluble isoflavone added milk were
      significantly different from uncapsuled water-soluble isoflavone added milk,
      however, bitterness was not significantly different. In vitro study, micro
      capsules of water-soluble isoflavone in simulated gastric fluid with the range of
      3 to 6 pHs were released 3.0-15.0%, however, the capsules in simulated intestinal
      fluid with pH 7 were released 95.7% for 40 min incubation time. In conclusion,
      this study provided that PGMS as coating materials was suitable for the
      microencapsulation of water-soluble isoflavone, and the capsule containing milk
      was almost not affected with sensory attribute.

PMID- 12785742
TI  - The basal ganglia: a neural network with more than motor function.
AB  - The basal ganglia is a group of subcortical nuclei involved in motor control,
      cognition, and emotion. Basal ganglia disorders are manifested by abnormal
      movement and a number of neuropsychiatric disorders. Basal ganglia nuclei are
      organized into sensorimotor, associative, and limbic territories based on their
      connectivity and function. The caudate nucleus, putamen, and subthalamic nucleus
      comprise the input nuclei of the basal ganglia. The internal segment of globus
      pallidus and substantia nigra reticulata are the output nuclei. The input and
      output nuclei are interconnected by direct and indirect pathways. The cerebral
      cortex, basal ganglia, and thalamus communicate with each other via closed
      (segregated) parallel as well as open (split) loops. Recent anatomic, functional,
      and clinical data have necessitated modifications in the classical models of
      local connectivity between input and output nuclei of the basal ganglia as well
      as in the corticobasal ganglia-thalamus-cortical loops.

PMID- 12785743
TI  - Sydenham's chorea: not gone and not forgotten.
AB  - Sydenham's chorea is an ancient disease that continues to afflict large numbers
      of children throughout the world. A major manifestation of rheumatic fever,
      Sydenham's chorea is commonly manifested by movement disorder and psychiatric
      problems, and also may be a marker for a life-threatening carditis. Because
      Sydenham's chorea is triggered by streptococcal pharyngitis, the most important
      component of its therapy is antibiotic prophylaxis against further streptococcal
      infections. Because the pathogenesis of Sydenham's chorea includes the production
      of anti-basal ganglia antibodies, therapies that modulate immune function or that
      restore neurotransmitter balance within the basal ganglia may be effective for
      Sydenham's chorea. Recent reports have suggested that Sydenham's chorea may be
      part of a spectrum of neuropsychiatric syndromes induced by streptococcal
      infection.

PMID- 12785744
TI  - Hereditary causes of chorea in childhood.
AB  - Chorea and athetosis are rare presenting symptoms in childhood. Chorea can be a
      presenting symptom in a number of hereditary diseases, including
      neurodegenerative diseases, paroxysmal diseases, and metabolic diseases. In these
      situations, family history, associated symptoms, and other physical findings will
      often enable a correct diagnosis. Benign childhood chorea is probably a
      genetically heterogeneous group of disorders, generally without other symptoms.
      Clinical aspects of these disorders are reviewed here.

PMID- 12785745
TI  - Tremor in children.
AB  - Tremor in childhood, beginning in the neonatal period, is more common than
      generally appreciated. Although some tremor disorders in children (eg, essential
      tremor) also affect adults, others (eg, shuddering, jitteriness, spasmus nutans,
      and vitamin B12-deficiency tremor) are seen exclusively in children. This review
      covers the etiology, clinical features, and treatment of the major tremor
      syndromes in children, and when appropriate, makes comparisons with similar
      disorders in adults.

PMID- 12785746
TI  - Tics and Tourette's syndrome in childhood.
AB  - Childhood tics are multidimensional in nature. The dimensions run along various
      continuums, including duration of symptoms (from fewer than 1 year to lifelong),
      intensity of symptoms (from mild to severe), frequency of symptoms (from rare to
      constant), variety of symptoms (from single motor groups/single phonic tic to
      multiple occurrences of both types), complexity of tics (from simple motor/phonic
      tic to multiple motor groups or the production of multiple sounds, including
      involuntary phrases), response to treatment (from good to minimal or no
      response), and comorbid psychiatric disorders (from none to multiple). This
      review describes these dimensions and their relationships to the current
      diagnostic scheme for tic disorders.

PMID- 12785747
TI  - Myoclonus in childhood.
AB  - The term "myoclonus" sounds esoteric, yet it is part of our normal physiology,
      occurring as a muscle jerk on drowsiness or falling asleep, during rapid eye
      movement (REM) sleep, and as hiccoughs. Myoclonus is also a developmental feature
      of the human nervous system, comprising some of the earliest fetal movements. In
      pathologic settings, myoclonus may be the only neurologic abnormality, as in
      essential myoclonus, but more often it is one symptom of a larger neurologic
      problem. The vast etiologic spectrum of symptomatic myoclonus can be bewildering,
      but defining the underlying problem may provide the opportunity to develop
      specific therapies. Otherwise, treatment is merely symptomatic. The approach to
      the patient should be to verify the nature of the movement disorder and establish
      a specific etiologic diagnosis. A battery of neurophysiologic, neuroradiologic,
      and other laboratory studies is needed to localize the origin of the myoclonus
      and identify causative lesions. Drug treatment is largely empiric but must be
      systematic and aimed at restoring activities of everyday living. Unlike in
      epilepsies, in myoclonus multiple drugs usually must be combined to attain
      functional improvement.

PMID- 12785748
TI  - Childhood dystonia.
AB  - Childhood dystonias are a heterogeneous group of disorders with strong inherited
      basis. This review describes the clinical characteristics, classification,
      genetic basis, pathophysiology, biochemistry, pathology, and treatment of
      dystonias, including the primary dystonias, the dystonia-plus syndromes,
      secondary dystonias, and heredodegenerative disorders. Conditions discussed in
      detail include idiopathic torsion dystonia, dopa-responsive dystonia, Wilson's
      disease, myoclonus dystonia, rapid-onset dystonia parkinsonism, neurodegeneration
      with brain iron accumulation (Hallervorden-Spatz syndrome), mitochondrial
      dystonias, Niemann-Pick type C, and neuroacanthocytosis.

PMID- 12785749
TI  - Juvenile parkinsonism.
AB  - Juvenile parkinsonism (JP) is a clinically and etiologically heterogeneous
      entity. Unlike in the adult form, secondary causes, hereditary and metabolic
      conditions, are the predominant causes of JP. Idiopathic Parkinson's disease is
      very rare in this age group. In most cases of JP, parkinsonism is accompanied by
      other neurologic features, such as dystonia, cognitive impairment, seizures,
      oculomotor and visual dysfunction, and ataxia. Systemic findings, such as liver
      dysfunction or hepatosplenomegaly, may be present depending on the cause. This
      review article describes the clinical characteristics, classification, genetic
      basis, pathophysiology, biochemistry, pathology, and treatment of JP.

PMID- 12785750
TI  - Paroxysmal kinesigenic dyskinesias.
AB  - The paroxysmal dyskinesias (PxDs) are involuntary, intermittent movement
      disorders manifested by dystonia, chorea, athetosis, ballismus or any combination
      of these hyperkinetic disorders. Paroxysmal kinesigenic dyskinesia (PKD), one of
      the four main types of PxD, involves sudden attacks of dyskinesias induced by
      voluntary movements. PKD most commonly occurs sporadically or as an autosomal
      dominant familial trait with variable penetrance. Many causes of secondary PKD
      are being recognized. The exact pathophysiology of the PxDs awaits further
      elucidation, although basal ganglia dysfunction appears to play a major role.
      Although the precise gene remains unknown, genetic linkage studies have isolated
      loci on chromosome 16, which colocalizes with the locus for familial infantile
      convulsions and paroxysmal choreoathetosis in some studies. The episodic nature
      of PKD and its relationship with other episodic diseases, such as epilepsy,
      migraine, and episodic ataxia, suggests channelopathy as a possible underlying
      etiology. PKD may remit spontaneously, but it also responds well to
      anticonvulsants as well as some other agents.

PMID- 12785751
TI  - Drug-induced movement disorders in children.
AB  - The increased use of stimulants, antipsychotic agents, and antidepressant drugs
      in children by primary care physicians, psychiatrists, and neurologists has
      inevitably led to increased numbers of pediatric patients manifesting the side
      effects of these agents, many of which are movement disorders. Unlike the
      isolated abnormal involuntary movements associated with drugs prescribed for
      epilepsy or asthma, movement syndromes (eg, acute dystonic reaction, neuroleptic
      malignant syndrome, serotonin syndrome, tardive dyskinesia) associated with
      psychotropic drugs are complex, difficult to recognize, and potentially seriously
      disabling. Accurate clinical identification of these drug-induced syndromes is
      critical to engaging the proper therapeutic intervention for them.

PMID- 12785752
TI  - Genetics of pediatric movement disorders.
AB  - Movement disorders in children often have a genetic basis. An explosion of
      genetic information in the past decade has led to the discovery of genetic
      defects in many forms of ataxia, parkinsonism, dystonia, tremor, and spastic
      paraparesis. This review focuses on genetically defined, early-onset diseases
      characterized primarily or exclusively by movement disorders. Particular emphasis
      is placed on disorders for which clinical or research testing is available.

PMID- 12785753
TI  - Basal ganglia calcifications in childhood.
AB  - In the advent of widespread use of neuroimaging, calcification of the basal
      ganglia is visualized with increasing frequency. In this monograph, modern
      neuroimaging features of various disorders causing basal ganglia calcification in
      childhood are illustrated and discussed.

PMID- 12785754
TI  - A forward look at therapy for pediatric movement disorders.
AB  - The mainstay of current therapy for pediatric movement disorders is oral
      symptomatic medication, unless a reversible etiology can be found. However, this
      approach is apt to pale in comparison with innovative strategies on the clinical
      forefront. Classical pharmacotherapy is restricted by the blood-brain barrier,
      which prevents access to the brain of potentially therapeutic molecules. Recent
      developments in molecular biotechnology include antibody-mediated drug release,
      feedback-responsive delivery systems, carrier-mediated transport, microspheres
      composed of polymers and liposomes, permeabilizers, and selective delivery to
      localized sites and vectors. Neuroprotective strategies for delivering
      neurotrophic factors and antiapoptotic and antioxidant molecules in
      neurodegenerative disorders are currently under study in clinical trials. Stem
      cell transplantation has great potential for tissue engineering and also as a
      carrier for gene therapy, although its use raises complex societal issues. These
      approaches, together with a plethora of transgenic knockout animal models of
      neurodegenerative disorders, offer real promise for a previously untreatable
      group of movement disorders.

PMID- 12785756
TI  - Helix-sense-selective polymerization of phenylacetylene having two hydroxy groups
      using a chiral catalytic system.
AB  - We have found a simple and novel synthetic method for obtaining a chiral polymer
      from an achiral monomer by using a chiral catalytic system. The chirality of the
      polymer was caused only by a one-handed helical backbone, and the polymer had no
      other chiral structures in the side groups. In addition, the helical conformation
      was stable in solution by itself. This is the first example of helix-sense
      selective polymerization of a substituted acetylene. The stability of the
      helicity was found to be caused by intramolecular hydrogen bonds.

PMID- 12785755
TI  - Enantioselective total synthesis of (+)-dibromophakellstatin.
AB  - The first enantioselective total synthesis of (+)-phakellstatin and (+)
      dibromophakellstatin was achieved. Key steps in the synthesis were a
      desymmetrization of the diketopiperazine (S,S)-cyclo (Pro, Pro) via a
      diastereoselective acylation, an intramolecular Mitsunobu reaction to introduce
      the C6 aminal, and a tandem Hofmann rearrangement/cyclization to simultaneously
      introduce the C10 quaternary aminal center and deliver the cyclic urea. The
      synthesis also demonstrates the unusual stability of pyrrolo aminals.
      Importantly, this strategy has the potential for producing phakellstatin
      derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological
      studies. A similar annulation protocol is also expected to be applicable to the
      synthesis of palau'amine.

PMID- 12785757
TI  - Reversal of the apparent regiospecificity of NAD(P)H-dependent hydride transfer:
      the properties of the difluoromethylene group, a carbonyl mimic.
AB  - The hallmarks of pyridine nucleotide-dependent dehydrogenase reactions are the
      stereo- and regiospecific hydride transfer between the nicotinamide coenzyme and
      the corresponding substrate. When the hydride is delivered from NAD(P)H to reduce
      the keto-substrate, the site of attack is always at the carbonyl carbon. However,
      the apparent regioselectivity of the hydride transfer is reversed when
      difluoromethylene is used as a carbonyl mimic in the NADH-dependent enzyme, TDP-l
      rhamnose synthase, which catalyzes the conversion of TDP-6-deoxy-l-lyxo-4
      hexulose to TDP-l-rhamnose. The observed reversed regioselectivity can be
      explained by two mechanisms. One involves the formation of a carbene intermediate
      followed by a rearrangement involving 1,2-H shift. This mechanistic proposal is
      theoretically sound and would represent a rare example implicating the
      intermediacy of a carbene species in an enzyme reaction. However, our results are
      also consistent with a second mechanism in which the hydride addition to the
      difluoromethylene moiety occurs at the difluorinated end, opposite from the site
      predicted on the basis of the reduction of a normal keto functional group. Such a
      regioselectivity is well precedented in chemical models because nucleophilic
      addition to fluoroalkenes prefers a route in which the number of fluorines beta
      to the electron-rich carbon in the transition state is maximized. In this
      mechanism, the difluoromethylene group may be regarded as a carbonyl mimic with
      reversed polarity in enzyme catalysis. While further experiments are needed to
      discriminate between these mechanistic possibilities, the results reported here
      suggest that the apparent regioselectivity of hydride transfer in a pyridine
      nucleotide-dependent enzyme can be changed by altering the electrochemical
      properties of the reaction center.

PMID- 12785758
TI  - pH- and thermosensitive supramolecular assembling system: rapidly responsive
      properties of beta-cyclodextrin-conjugated poly(epsilon-lysine).
AB  - beta-Cyclodextrin-conjugated poly(epsilon-lysine) (beta-CDPL) was synthesized as
      a novel polymeric host for constructing a smart supramolecular assembling system.
      Systematic studies on the inclusion complexation between the polymeric host with
      an alpha- or beta-CD cavity and a model guest molecule provided evidence that
      dual cooperative interactions, specific host-guest interaction and intermolecular
      ionic interaction, played a dominant role in leading to a fast aggregation
      phenomenon. In addition, a rapid phase transition induced by the supramolecular
      assembly was observed reversibly in response to a small change in pH or
      temperature.

PMID- 12785759
TI  - Vanadium-binding protein in a vanadium-rich ascidian Ascidia sydneiensissamea: CW
      and pulsed EPR studies.
AB  - Some of the ascidians belonging to the suborder Phlebobranchia accumulate
      vanadium ion efficiently from seawater. Clarification of the mechanism of this
      surprisingly efficient metal-accumulation system is desirable. Two mutually
      similar vanadium-binding proteins (vanabin1 and vanabin2) have recently been
      isolated from a vanadium-rich ascidian Ascidia sydneiensis samea. In this study,
      the vanadium-binding properties of vanabin2 have been investigated by X-band CW
      EPR and pulsed EPR spectroscopy. CW EPR spectra of samples containing various
      ratios of VO2+ and vanabin2 invariably exhibited a usual mononuclear-type VO2+
      EPR signal with the intensity dependent on the ratio [vanabin]/[V]. EPR titration
      has shown that vanabin2 can bind up to approximately 23.9 vanadium ions per one
      molecule, almost all of which ( approximately 84%) are in a mononuclear VO2+
      state as estimated by EPR quantitation. Electron spin-echo envelope modulation
      (ESEEM) spectra of VO-vanabin2 exhibited reasonably intense peaks attributable to
      amine nitrogen. This is consistent with the fact that vanabin2 is a lysine-rich
      protein (14 lysines out of 91 amino acids). The present study reveals the
      uniqueness of vanabin2, which can bind a large number of metal ions in a
      mononuclear fashion in contrast to the situation for ferritin and
      metallothionein.

PMID- 12785761
TI  - Cationic terminal borylenes by halide abstraction: synthesis and spectroscopic
      and structural characterization of an Fe=B double bond.
AB  - The synthesis and the spectroscopic and structural characterization of the
      cationic terminal borylene complex [Cp*Fe(CO)2(BMes)]+ are reported. Halide
      abstraction from the corresponding bromoboryl species using Na[BAr f4] generates
      the borylene as the [BAr f4]- salt in ca. 50% yield. Analyses of IR, NMR,
      crystallographic, and DFT data are consistent with the presence of an Fe=B double
      bond.

PMID- 12785760
TI  - Metal incorporation in modified PNA duplexes.
AB  - Substitution of bipyridine for a nucleobase leads to modified peptide nucleic
      acid (PNA) single strands that are bridged in the presence of Ni2+ into a duplex
      containing a combination of hydrogen and coordinative bonds. CD experiments
      demonstrate that the duplex adopts a structure similar to that of an unmodified
      10-bp PNA duplex, and UV melting experiments show a very sensitive dependence of
      the duplex stability on the substitution of a nucleobase pair with a pair of
      ligands or a metal-ligand alternative base pair.

PMID- 12785762
TI  - Palladium- and nickel-catalyzed intramolecular cyanoboration of alkynes.
AB  - Intramolecular addition of a boron-cyano bond across a carbon-carbon triple bond
      was achieved using palladium and nickel catalysts. Cyano(diisopropylamino)boryl
      homopropargyl ethers underwent regio- and stereoselective 5-exo cyclization,
      forming five-membered cyclic boryl ethers in high yields. The cyanoboration
      products thus obtained served as new precursors for the synthesis of highly
      substituted alpha,beta-unsaturated nitriles via transition-metal-catalyzed
      transformations.

PMID- 12785763
TI  - Complexation promoted additions to N-benzoyliminopyridinium ylides. A novel and
      highly regioselective approach to polysubstituted piperidines.
AB  - Unprecedented regioselectivities were observed for the addition of different
      organometallic nucleophiles to N-benzoyliminopyridinium ylides. Even benzylic and
      branched aliphatic Grignard reagents, which usually give substantial amounts of
      1,4-adducts, showed excellent 1,2-regioselectivities. The electronic nature of
      the pyridinium ylide is taken into account to explain these results.

PMID- 12785764
TI  - Enantioselective synthesis of alpha-substituted ketones by asymmetric addition of
      chiral zinc enamides to 1-alkenes.
AB  - A zinc enamide of a chiral imine derived from a ketone and (S)-valinol or (S)-t
      leucinol undergoes addition to 1-alkene to generate a gamma-zincioimine
      intermediate, which reacts with a carbon electrophile to give upon hydrolysis an
      optically active alpha-substituted ketone in good yield. The stereoselectivity of
      the addition reaction may reach 99% for the reaction of a cyclohexanone imine
      with ethylene.

PMID- 12785765
TI  - pH-triggered strand exchange in coiled-coil heterotrimers.
AB  - The capacity for pH-triggered strand exchange in designed coiled-coil
      heterotrimers is demonstrated. Systems employing both hydrophobic core (steric
      matching) and hydrophilic interface (electrostatic matching) design principles
      assemble into specific 1:1:1 heterotrimers. Alteration of pH creates
      electrostatic mismatches, inducing strand exchange in the presence of a suitable
      replacement peptide. Complexes with one Lys/Lys interface, favored at neutral to
      high pH, can be transformed to ones with a Glu/Glu contact by lowering pH and
      adding an appropriate new binding partner. The need to simultaneously maintain
      matched core alignments enforces specificity in this exchange, such that only a
      single specific peptide is replaced. These principles have subsequently been
      applied to the design of dynamically triggered cross-linked structures, in which
      a bifunctional disulfide-tethered peptide can cross-link two heterotrimers. Both
      formation and disruption of the cross-link are under pH control.

PMID- 12785766
TI  - Catalytic alcoholysis of tetramethylsilane via Pt-mediated C-H bond activation.
AB  - Tetramethylsilane reacts with 2,2,2-trifluoroethanol (TFE) in the presence of a
      cationic platinum(II) catalyst [(NN)PtMe(TFE)]+ (NN = 1,2-bis(3,5
      dimethylphenylimino)butane). Catalytic Si-C bond heterolysis results in the
      formation of the trimethylsilyl ether, Me3SiOCH2CF3, accompanied by liberation of
      one equivalent of methane. Preliminary experiments suggest that a rate
      determining C-H bond activation precedes rapid attack by solvent at silicon to
      yield the silyl ether product and regenerate the active platinum methyl cation.

PMID- 12785768
TI  - Novel rhodium-catalyzed cycloisomerization of 1,6-enynes with an intramolecular
      halogen shift.
AB  - A new Rh-catalyzed 1,6-enyne cycloisomerization process with a pi-allyl rhodium
      species as the key intermediate is investigated. A halogen shift happened in this
      novel process. The synthesis of stereodefined alpha-halomethylene gamma
      butyrolactones has been achieved using the readily accessible Rh catalysts.

PMID- 12785767
TI  - Directed self-assembly of two kinds of nanoparticles utilizing monolayer films of
      diblock copolymer micelles.
AB  - We demonstrated a self-assembly of two different kinds of nanoparticles
      simultaneously directed on a monolayer film of diblock copolymer micelles via
      physical and chemical arrangements. We first incorporated gold nanoparticles
      physically around the micelles of a monolayer film of PS-PVP micelles having a
      short-range hexagonal order. Iron oxide nanoparticles were then synthesized
      chemically in the PVP core area of the ordered micelles, resulting in a mosaic
      nanopattern of magnetic iron oxide nanoparticles surrounded by metallic gold
      nanoparticles. Thus, we were able to direct two kinds of nanoparticles to self
      assemble in the specific positions as an example of controlled fabrication of
      nanometer-sized building blocks.

PMID- 12785769
TI  - A hydroacylation-triggered carbon--carbon triple bond cleavage in alkynes via
      retro-Mannich type fragmentation.
AB  - The carbon-carbon triple bond in alkyne is cleaved via hydroacylation followed by
      retro-Mannich type fragmentation in the presence of aldehyde, which triggers a
      successive C-C bond cleavage.

PMID- 12785770
TI  - Gold nanoparticles as spectroscopic enhancers for in vitro studies on single
      viruses.
AB  - Gold particles with diameters between 2.5 and 4.5 nm have been introduced in the
      inner cavity of an icosahedral brome mosaic virus. The optical properties of
      single gold-marked virions have been tested in-vitro with respect to the
      characteristic plasmon polariton resonance. The shift in the plasmon polariton
      resonance of a single Au particle encapsulated in a virus with respect to a free
      particle in solution indicates a close interaction between the basic residues on
      the inner wall of the capsid and the negative surface charge of the particle.
      Incorporation of a pair of Au particles, approximately 4 nm diameter, is shown to
      be a frequent event. In this case, the dependence of the two-particle surface
      plasmon spectrum on the interparticle distance and the strong particle/capsid
      wall interaction suggest that, in the future, it will be possible to use
      encapsulated Au particles to track changes in the viral capsid volume in real
      time and in a physiological environment.

PMID- 12785771
TI  - Preparation of unidirectional end-grafted alpha-helical polypeptides by solvent
      quenching.
AB  - A simple "solvent quenching" approach to align an alpha-helical end-grafted
      poly(gamma-benzyl l-glutamate) monolayer is presented. By sequentially treating
      poly(gamma-benzyl l-glutamate) with good solvent (chloroform) and bad solvent
      (acetone), we obtained a highly aligned monolayer with an average tilt angle as
      small as 3 degrees .

PMID- 12785772
TI  - Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids.
AB  - DNA helix invasion by P-loop forming peptide nucleic acids (PNAs) is extremely
      sensitive to increased ionic strength as this stabilizes the DNA duplex. To
      address this, the DNA intercalator 9-aminoacridine was conjugated to helix
      invading PNAs, and the duplex DNA binding efficiency of such constructs was
      measured at different ionic strength conditions by electrophoretic mobility shift
      analysis. Remarkably, at physiogically relevant ionic strength (140 mM K+/10 mM
      Na+, 2 mM Mg2+), acridine conjugated PNAs showed 20-150-fold superior binding to
      a cognate sequence target as compared to the conventional PNAs. This enhancement
      occurred without compromising the sequence specificity of binding. Thus, simply
      conjugating the DNA intercalator 9-aminoacridine to PNA represents a major step
      toward the development of helix invading constructs for in vivo applications such
      as gene targeting.

PMID- 12785773
TI  - Nucleation of one polymorph by another.
AB  - Nucleation of one polymorph by another has been observed directly in the melt
      crystallization of d-mannitol and d-sorbitol. The new polymorph nucleated on an
      existing one and grew to dominate the end product. This effect is relevant to
      controlling polymorphism in the manufacture of specialty chemicals and to
      developing theories of polymorphic nucleation and concomitant polymorphs, for
      which current efforts emphasize homogeneous nucleation of alternative polymorphs.

PMID- 12785774
TI  - Simulation of pore formation in lipid bilayers by mechanical stress and electric
      fields.
AB  - We describe computer simulations of pore formation and membrane rupture of
      phospholipid bilayers under mechanical and electrical stress. On the nanosecond
      simulation time scale, pores are induced by a lateral pressure exceeding -200 bar
      or by an applied electric field of 0.5 V/nm.

PMID- 12785775
TI  - Diradical mechanism for the [2 + 2] cycloaddition of ethylene on Si(100) surface.
AB  - Density functional cluster model calculations have been performed to explore the
      reaction mechanism for the adsorption of ethylene on Si(100). It is shown that
      the [2 + 2] cycloaddition of ethylene on a Si=Si dimer of Si (100) surface
      follows a diradical mechanism, via a pi-complex precursor and a singlet diradical
      intermediate, and the rate-determining step for the overall reaction is the
      formation of the diradical intermediate.

PMID- 12785776
TI  - Interfacial synthesis of hollow TiO2 microspheres in ionic liquids.
AB  - An interfacial sol-gel synthesis of inorganic hollow microspheres in room
      temperature ionic liquids is newly developed. When metal alkoxides such as
      titanium tetrabutoxide, Ti(OBu)4, are dissolved in anhydrous toluene and injected
      into 1-buthyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6) under vigorous
      stirring, hollow titania microspheres are formed. The present technique is widely
      applicable to the reactive metal alkoxides such as Zr(OBu)4, Hf(OBu)4, Nb(OBu)4,
      and InSn3(OR)x, giving a general route to the metal oxide microspheres. When gold
      nanoparicles and carboxylate-containing dyes such as fluorescein isothiocyanate
      (FITC) are dissolved in the toluene microdroplets, they are stably immobilized in
      the microsphere shells. Calcination of the titania gel microspheres gives anatase
      TiO2 microspheres. The present method provides the first example of inorganic
      hollow microspheres formed in ionic liquids, and the ability to modify
      microspheres with metal nanoparticles or functional organic molecules would be
      widely applied to the design of smart organic/inorganic hybrid materials.

PMID- 12785777
TI  - Triflimide activation of a chiral oxazaborolidine leads to a more general
      catalytic system for enantioselective Diels-Alder addition.
AB  - The strong acid triflimide ((CF3SO2)2NH) protonates chiral oxazaborolidines to
      form superactive, stable, chiral Lewis acids which are highly effective catalysts
      for a wide variety of enantioselective Diels-Alder reactions, documented herein
      by more than 20 examples.

PMID- 12785778
TI  - Exploiting amyloid fibril lamination for nanotube self-assembly.
AB  - Fundamental questions about the relative arrangement of the beta-sheet arrays
      within amyloid fibrils remain central to both its structure and the mechanism of
      self-assembly. Recent computational analyses suggested that sheet-to-sheet
      lamination was limited by the length of the strand. On the basis of this
      hypothesis, a short seven-residue segment of the Alzheimer's disease-related
      Abeta peptide, Abeta(16-22), was allowed to self-assemble under conditions that
      maintained the basic amphiphilic character of Abeta. Indeed, the number increased
      over 20-fold to 130 laminates, giving homogeneous bilayer structures that
      supercoil into long robust nanotubes. Small-angle neutron scattering and X-ray
      scattering defined the outer and inner radii of the nanotubes in solution to
      contain a 44-nm inner cavity with 4-nm-thick walls. Atomic force microscopy and
      transmission electron microscopy images further confirmed these homogeneous
      arrays of solvent-filled nanotubes arising from a flat rectangular bilayer, 130
      nm wide x 4 nm thick, with each bilayer leaflet composed of laminated beta
      sheets. The corresponding backbone H-bonds are along the long axis, and beta
      sheet lamination defines the 130-nm bilayer width. This bilayer coils to give the
      final nanotube. Such robust and persistent self-assembling nanotubes with
      positively charged surfaces of very different inner and outer curvature now offer
      a unique, robust, and easily accessible scaffold for nanotechnology.

PMID- 12785779
TI  - Spectroscopy and bonding in side-on and end-on Cu2(S2) cores: comparison to
      peroxide analogues.
AB  - Spectroscopic methods combined with density functional calculations were used to
      study the disulfide-Cu(II) bonding interactions in the side-on micro 
      eta(2):eta(2)-bridged Cu(2)(S(2)) complex, [[Cu(II)[HB(3,5
      Pr(i)(2)pz)(3)]](2)(S(2))], and the end-on trans- micro -1,2-bridged Cu(2)(S(2))
      complex, [[Cu(II)(TMPA)](2)(S(2))](2+), in correlation to their peroxide
      structural analogues. Resonance Raman shows weaker S-S bonds and stronger Cu-S
      bonds in the disulfide complexes relative to the O-O and Cu-O bonds in the
      peroxide analogues. The weaker S-S bonds come from the more limited interaction
      between the S 3p orbitals relative to that of the O 2s/p hybrid orbitals. The
      stronger Cu-S bonds result from the more covalent Cu-disulfide interactions
      relative to the Cu-peroxide interactions. This is consistent with the higher
      energy of the disulfide valence level relative to that of the peroxide. The
      ground states of the side-on Cu(2)(S(2))/Cu(2)(O(2)) complexes are more covalent
      than those of the end-on Cu(2)(S(2))/Cu(2)(O(2)) complexes. This derives from the
      larger sigma-donor interactions in the side-on micro -eta(2):eta(2) structure,
      which has four Cu-disulfide/peroxide bonds, relative to the end-on trans- micro 
      1,2 structure, which forms two bonds to the Cu. The larger disulfide/peroxide
      sigma-donor interactions in the side-on complexes are reflected in their more
      intense higher energy disulfide/peroxide to Cu charge transfer transitions in the
      absorption spectra. The large ground-state covalencies of the side-on complexes
      result in significant nuclear distortions in the ligand-to-metal charge transfer
      excited states, which give rise to the strong resonance Raman enhancements of the
      metal-ligand and intraligand vibrations. Particularly, the large covalency of the
      Cu-disulfide interaction in the side-on Cu(2)(S(2)) complex leads to a different
      rR enhancement profile, relative to the peroxide analogues, reflecting a S-S bond
      distortion in the opposite directions in the disulfide/peroxide pi(sigma) to Cu
      charge transfer excited states. A ligand sigma back-bonding interaction exists
      only in the side-on complexes, and there is more sigma mixing in the side-on
      Cu(2)(S(2)) complex than in the side-on Cu(2)(O(2)) complex. This sigma back
      bonding is shown to significantly weaken the S-S/O-O bond relative to that of the
      analogous end-on complex, leading to the low nu(S)(-)(S)/nu(O)(-)(O) vibrational
      frequencies observed in the resonance Raman spectra of the side-on complexes.

PMID- 12785781
TI  - Effect of 3-hydroxyproline residues on collagen stability.
AB  - Collagen is an integral part of many types of connective tissue in animals,
      especially skin, bones, cartilage, and basement membranes. A fibrous protein,
      collagen has a triple-helical structure, which is comprised of strands with a
      repeating Xaa-Yaa-Gly sequence. l-Proline (Pro) and 4(R)-hydroxy-l-proline (4
      Hyp) residues occur most often in the Xaa and Yaa positions. The 4-Hyp residue is
      known to increase markedly the conformational stability of a collagen triple
      helix. In natural collagen, a 3(S)-hydroxy-l-proline (3-Hyp) residue occurs in
      the sequence: 3-Hyp-4-Hyp-Gly. Its effect on collagen stability is unknown. Here,
      two host-guest peptides containing 3-Hyp are synthesized: (Pro-4-Hyp-Gly)(3)-3
      Hyp-4-Hyp-Gly-(Pro-4-Hyp-Gly)(3) (peptide 1) and (Pro-4-Hyp-Gly)(3)-Pro-3-Hyp-Gly
      (Pro-4-Hyp-Gly)(3) (peptide 2). The 3-Hyp residues in these two peptides diminish
      triple-helical stability in comparison to Pro. This destabilization is small when
      3-Hyp is in the natural Xaa position (peptide 1). There, the inductive effect of
      its 3-hydroxyl group diminishes slightly the strength of the interstrand 3
      HypC=O.H-NGly hydrogen bond. The destabilization is large when 3-Hyp is in the
      nonnatural Yaa position (peptide 2). There, its pyrrolidine ring pucker leads to
      inappropriate mainchain dihedral angles and interstrand steric clashes. Thus, the
      natural regioisomeric residues 3-Hyp and 4-Hyp have distinct effects on the
      conformational stability of the collagen triple helix.

PMID- 12785780
TI  - Polyunsaturated docosahexaenoic vs docosapentaenoic acid-differences in lipid
      matrix properties from the loss of one double bond.
AB  - Insufficient supply to the developing brain of docosahexaenoic acid (22:6n3,
      DHA), or its omega-3 fatty acid precursors, results in replacement of DHA with
      docosapentaenoic acid (22:5n6, DPA), an omega-6 fatty acid that is lacking a
      double bond near the chain's methyl end. We investigated membranes of 1
      stearoyl(d(35))-2-docosahexaenoyl-sn-glycero-3-phosphocholine and 1
      stearoyl(d(35))-2-docosapentaenoyl-sn-glycero-3-phosphocholine by solid-state
      NMR, X-ray diffraction, and molecular dynamics simulations to determine if the
      loss of this double bond alters membrane physical properties. The low order
      parameters of polyunsaturated chains and the NMR relaxation data indicate that
      both DHA and DPA undergo rapid conformational transitions with correlation times
      of the order of nanoseconds at carbon atom C(2) and of picoseconds near the
      terminal methyl group. However, there are important differences between DHA- and
      DPA-containing lipids: the DHA chain with one additional double bond is more
      flexible at the methyl end and isomerizes with shorter correlation times.
      Furthermore, the stearic acid paired with the DHA in mixed-chain lipids has lower
      order, in particular in the middle of the chain near carbons C(10)(-)(12),
      indicating differences in the packing of hydrocarbon chains. Such differences are
      also reflected in the electron density profiles of the bilayers and in the
      simulation results. The DHA chain has a higher density near the lipid-water
      interface, whereas the density of the stearic acid chain is higher in the bilayer
      center. The loss of a single double bond from DHA to DPA results in a more even
      distribution of chain densities along the bilayer normal. We propose that the
      function of integral membrane proteins such as rhodopsin is sensitive to such a
      redistribution.

PMID- 12785782
TI  - Surfaces designed for charge reversal.
AB  - We have created surfaces which switch from cationic at pH < 3 to anionic at pH >
      5, by attaching aminodicarboxylic acid units to silica and gold substrates.
      Charge reversal was demonstrated by monitoring the adsorption of cationic dyes
      (methylene blue and a tetracationic porphyrin) and an anionic sulfonated
      porphyrin, at a range of pH using UV-vis absorption and reflection spectroscopy.
      The cationic dyes bind under neutral conditions (pH 5-7) and are released at pH 1
      4, whereas the anionic dye binds under acidic conditions (pH 1-4) and is released
      at pH 5-7. Gold surfaces were functionalized with two different amphoteric
      disulfides with short (CH(2))(2) and long (CH(2))(10)CONH(CH(2))(6) linkers; the
      longer disulfide gave surfaces exhibiting charge reversal in a narrower pH range.
      Adsorption is much faster on the functionalized gold (t(1/2) = 62 s) than on
      functionalized silica (t(1/2) = 6900 s), but the final extents of coverage on
      both surface are similar, for a given dye at a given pH, with maximal coverages
      of around 2 molecules nm(-)(2). These charge-reversal processes are reversible
      and can be repeatedly cycled by changing the pH. We have also created surfaces
      which undergo irreversible proton-triggered charge switching, using a carbamate
      linked thiol carboxylic acid which cleaves in acid. These surfaces are versatile
      new tools for controlling electrostatic self-assembly at surfaces.

PMID- 12785784
TI  - Supramolecular assembly of poly(phenylene vinylene) with crown ether substituents
      to form nanoribbons.
AB  - Poly(para-phenylene vinylene) with crown ether substituents (C-PPV) could form
      nanoribbons through supramolecular assembly with K(+) in dilute chloroform
      solution. The length of the nanoribbons increased with an increase in the
      standing time of the C-PPV/K(+) solution. Experimental evidence to support the
      interaction between K(+) and crown ether substituents was provided, and the
      growth mechanism of C-PPV/K(+) nanorods to nanoribbons was proposed. The
      influence of the length of the nanoribbons on the photophysics of C-PPV was also
      investigated.

PMID- 12785783
TI  - Metal-ligand charge-transfer-promoted photoelectronic Bergman cyclization of
      copper metalloenediynes: photochemical DNA cleavage via C-4' H-atom abstraction.
AB  - Metal-to-ligand charge-transfer (MLCT) photolyses (lambda > or = 395 nm) of
      copper complexes of cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne (bpod, 1),
      [Cu(bpod)(2)]PF(6) (2), and [Cu(bpod)(2)](NO(3))(2) (3) yield Bergman cyclization
      of the bound ligands. In contrast, the uncomplexed ligand 1 and
      Zn(bpod)(2)(CH(3)COO)(2) compound (4) are photochemically inert under the same
      conditions. In the case of 4, sensitized photochemical generation of the lowest
      energy (3)pi-pi state, which is localized on the enediyne unit, leads to
      production of the trans-bpod ligand bound to the Zn(II) cation by
      photoisomerization. Electrochemical studies show that 1, both the uncomplexed and
      complexed, exhibits two irreversible waves between E(p) values of -1.75 and -1.93
      V (vs SCE), corresponding to reductions of the alkyne units. Irreversible, ligand
      based one-electron oxidation waves are also observed at +1.94 and +2.15 V (vs
      SCE) for 1 and 3. Copper-centered oxidation of 2 and reduction of 3 occur at
      E(1/2) = +0.15 and +0.38 V, respectively. Combined with the observed Cu(I)-to
      pyridine(pi) MLCT and pyridine(pi)-to-Cu(II) ligand-to-metal charge transfer
      (LMCT) absorption centered near approximately 315 nm, the results suggest a
      mechanism for photo-Bergman cyclization that is derived from energy transfer to
      the enediyne unit upon charge-transfer excitation. The intermediates produced
      upon photolysis degrade both pUC19 bacterial plasmid DNA, as well as a 25-base
      pair, double-stranded oligonucleotide. Detailed analyses of the cleavage
      reactions reveal 5'-phosphate and 3'-phosphoglycolate termini that are derived
      from H-atom abstraction from the 4'-position of the deoxyribose ring rather than
      redox-induced base oxidation.

PMID- 12785785
TI  - A novel family of ordered, mesoporous inorganic/organic hybrid polymers
      containing covalently and multiply bound microporous organic hosts.
AB  - We have prepared a new family of periodic hybrid polymers containing microporous
      cavities provided by covalently bound organic hosts. Cyclodextrin (CD) or
      calixarene (CX) hosts are attached to four or more trialkoxysilyl groups, which
      are polymerized to form a polysilsesquioxane matrix. Structural integrity is
      provided by copolymerization with tetraethoxysilane, which produces a
      polysilicate co-matrix. Periodic order is created by carrying out the
      polymerization in the presence of a surfactant, cetyltrimethylammonium bromide.
      The resulting as-synthesized polymers from these three starting materials were
      characterized by solid-state nuclear magnetic resonance spectroscopy. The (13)C
      and (29)Si spectra provided evidence for intact polysilsesquioxane, polysilicate,
      organic host, and surfactant. Removal of the surfactant by washing produced a
      polymer containing cavities of mesoporous dimensions, in addition to the
      microporous host cavities. The purpose of introducing mesoporosity is to allow
      enhanced access of guests to the microporous hosts. Transmission electron
      microscopy demonstrated that both as-synthesized and solvent-extracted polymers
      have a periodic structure. All polymers are completely insoluble in water. The as
      synthesized CD-containing polymers extracted up to >99% of 4-nitrophenol from
      aqueous solution, and the solvent-extracted CX-containing polymers extracted up
      to 67% of Fe(3+) and lesser amounts of other metal cations from aqueous solution,
      with interesting selectivity patterns. Simple filtration then removes the polymer
      containing the extracted organic molecule or metal cation. These extraction
      abilities are superior to previous materials.

PMID- 12785786
TI  - New strategic reactions for organic synthesis: catalytic asymmetric C-H
      activation alpha to nitrogen as a surrogate for the mannich reaction.
AB  - The asymmetric C-H activation reactions of methyl aryldiazoacetates are readily
      induced by the rhodium prolinate catalyst Rh(2)(S-DOSP)(4) (1) or the bridged
      prolinate catalysts Rh(2)(S-biDOSP)(2) (2a) and Rh(2)(S-biTISP)(2) (2b). The C-H
      activation of N-Boc-protected cyclic amines demonstrates that the donor/acceptor
      substituted carbenoids display remarkable chemoselectivity, which allows for
      highly regioselective, diastereoselective, and enantioselective reactions to be
      achieved. Furthermore, the reactions can display high levels of double
      stereodifferentiation and kinetic resolution. The C-H activation is caused by a
      rhodium carbenoid induced C-H insertion. The potential of this chemistry is
      demonstrated by a very direct synthesis of threo-methylphenidate.

PMID- 12785787
TI  - Aminoglycoside complexation with a DNA.RNA hybrid duplex: the thermodynamics of
      recognition and inhibition of RNA processing enzymes.
AB  - Spectroscopic and calorimetric techniques were employed to characterize and
      contrast the binding of the aminoglycoside paromomycin to three octamer nucleic
      acid duplexes of identical sequence but different strand composition (a DNA.RNA
      hybrid duplex and the corresponding DNA.DNA and RNA.RNA duplexes). In addition,
      the impact of paromomycin binding on both RNase H- and RNase A-mediated cleavage
      of the RNA strand in the DNA.RNA duplex was also determined. Our results reveal
      the following significant features: (i) Paromomycin binding enhances the thermal
      stabilities of the RNA.RNA and DNA.RNA duplexes to similar extents, with this
      thermal enhancement being substantially greater in magnitude than that of the
      DNA.DNA duplex. (ii) Paromomycin binding to the DNA.RNA hybrid duplex induces CD
      changes consistent with a shift from an A-like to a more canonical A
      conformation. (iii) Paromomycin binding to all three octamer duplexes is linked
      to the uptake of a similar number of protons, with the magnitude of this number
      being dependent on pH. (iv) The affinity of paromomycin for the three host
      duplexes follows the hierarchy, RNA.RNA > DNA.RNA >> DNA.DNA. (v) The observed
      affinity of paromomycin for the RNA.RNA and DNA.RNA duplexes decreases with
      increasing pH. (vi) The binding of paromomycin to the DNA.RNA hybrid duplex
      inhibits both RNase H- and RNase A-mediated cleavage of the RNA strand. We
      discuss the implications of our combined results with regard to the specific
      targeting of DNA.RNA hybrid duplex domains and potential antiretroviral
      applications.

PMID- 12785788
TI  - The 2-oxocyclohexanecarboxylic acid keto-enol system in aqueous solution.
AB  - Flash photolysis of 2-diazocycloheptane-1,3-dione or 2,2-dimethyl-5,6,7,8
      tetrahydrobenzo-4H-1,3-dioxin-4-one in aqueous solution produced 2
      oxocyclohexylideneketene, which underwent hydration to the enol of 2
      oxocyclohexanecarboxylic acid, and the enol then isomerized to the keto form of
      the acid. Isomerization of the enol to keto forms was also observed using solid
      enol, a substance heretofore commonly believed to be the keto acid. Rates of
      ketonization were measured in perchloric acid, sodium hydroxide, and buffer
      solutions, and a ketonization rate profile was constructed. Rates of enolization
      of the keto acid were also measured using bromine to scavenge the enol as it
      formed. Rates of enolization and ketonization were then combined to provide the
      keto-enol equilibrium constant pK(E) = 1.27. This and some of the other results
      obtained are different from the corresponding quantities for the 2
      oxocyclopentanecarboxylic acid keto-enol system. These differences are discussed.

PMID- 12785789
TI  - A m-benzyne to o-benzyne conversion through a 1,2-shift of a phenyl group.
AB  - Pyrolysis of two differently labeled versions of 3-phenylphthalic anhydride shows
      that a m-benzyne can form the related o-benzyne through shift of a phenyl group.
      The highest energy point in the process is the transition structure for a reverse
      carbon-hydrogen insertion in an intermediate benzopentalene. With the minor
      addition of an intermediate alkyne formed through a Roger Brown rearrangement,
      the original mechanism for formation of acenaphthalene accommodates the labeling
      results.

PMID- 12785790
TI  - Nanoparticle-cored dendrimers: synthesis and characterization.
AB  - The synthesis and characterization of a group of new dendrimers-namely,
      nanoparticle-cored dendrimers (NCDs)-are described. These materials were obtained
      by the reduction of hydrogen tetrachloroaurate phase-transferred into toluene in
      the presence of Frechet-type polyaryl ether dendritic disulfide wedges of
      generation 1-5. These materials, possessing nanometer-sized gold clusters at the
      core and dendritic wedges radially connected to the core by Au-S bonds, were
      analyzed by TEM and TGA, and by UV, IR, and NMR spectroscopies. The number of
      branching units connected to the core decreased with the generation of the
      dendritic wedge, and this number changed from 2.18/nm(2) for Au-G-2 to 0.27/nm(2)
      for Au-G-5. This result suggests that, in the higher-generation NCDs, a large
      fraction of the surface area of the metal cluster is not passivated and is
      therefore available for catalytic activity.

PMID- 12785791
TI  - Universal iterative strategy for the divergent synthesis of dendritic
      macromolecules from conventional monomers by a combination of living radical
      polymerization and irreversible TERminator multifunctional INItiator (TERMINI).
AB  - A new synthetic concept named TERMINI that stands for irreversible TERminator
      Multifunctional INItiator is reported. Suitable combinations of TERMINI and
      living polymerizations provide access to strategies for the design and synthesis
      of unprecedented complex molecular and macromolecular architectures from a
      diversity of commercial monomers. TERMINI represents a masked multifunctional
      initiator designed to quantitatively and irreversibly interrupt a chain organic
      reaction or a living polymerization. After demasking, the TERMINI repeat unit
      enables the quantitative reinitiation, in the presence or absence of a catalyst,
      of the same or a different living polymerization or a chain organic reaction in
      more than one direction, thus becoming a branching point. The demonstration of
      this concept was made by using a combination of metal-catalyzed living radical
      polymerization (LRP) and (1,1-dimethylethyl)[[1-[3,5-bis(S-phenyl 4-N,N'
      diethylthiocarbamate)phenyl]ethenyl]oxy]dimethylsilane as TERMINI, to elaborate a
      novel iterative divergent method for the synthesis of dendritic macromolecules
      based on methyl methacrylate (MMA).

PMID- 12785793
TI  - Metallacarbenes from diazoalkanes: an experimental and computational study of the
      reaction mechanism.
AB  - PCP ligand (1,3-bis-[(diisopropyl-phosphanyl)-methyl]-benzene), and PCN ligand
      ([3-[(di-tert-butyl-phosphanyl)-methyl]-benzyl]-diethyl-amine) based rhodium
      dinitrogen complexes (1 and 2, respectively) react with phenyl diazomethane at
      room temperature to give PCP and PCN-Rh carbene complexes (3 and 5,
      respectively). At low temperature (-70 degrees C), PCP and PCN phenyl
      diazomethane complexes (4 and 6, respectively) are formed upon addition of phenyl
      diazomethane to 1 and 2. In these complexes, the diazo moiety is eta(1)
      coordinated through the terminal nitrogen atom. Decomposition of complexes 4 and
      6 at low temperatures leads only to a relatively small amount of the
      corresponding carbene complexes, the major products of decomposition being the
      dinitrogen complexes 1 and 2 and stilbene. This and competition experiments
      (decomposition of 6 in the presence of 1) suggests that phenyl diazomethane can
      dissociate under the reaction conditions and attack the metal center through the
      diazo carbon producing a eta(1)-C bound diazo complex. Computational studies
      based on a two-layer ONIOM model, using the mPW1K exchange-correlation functional
      and a variety of basis sets for PCP based systems, provide mechanistic insight.
      In the case of less bulky PCP ligand bearing H-substituents on the phosphines, a
      variety of mechanisms are possible, including both dissociative and
      nondissociative pathways. On the other hand, in the case of i-Pr substituents,
      the eta(1)-C bound diazo complex appears to be a critical intermediate for
      carbene complex formation, in good agreement with the experimental results. Our
      results and the analysis of reported data suggest that the outcome of the
      reaction between a diazoalkane and a late transition metal complex can be
      anticipated considering steric requirements relevant to eta(1)-C diazo complex
      formation.

PMID- 12785792
TI  - Multivalent drug design. Synthesis and in vitro analysis of an array of
      vancomycin dimers.
AB  - The design, synthesis, and in vitro microbiological analysis of an array of forty
      covalently linked vancomycin dimers are reported. This work was undertaken to
      systematically probe the impact of linkage orientation and linker length on
      biological activity against susceptible and drug-resistant Gram-positive
      pathogens. To prepare the array, monomeric vancomycin synthons were linked
      through four distinct positions of the glycopeptide (C-terminus (C), N-terminus
      (N), vancosamine residue (V), and resorcinol ring (R)) in 10 unique pairwise
      combinations. Amphiphilic, peptide-based linkers of four different lengths (11,
      19, 27, and 43 total atoms) were employed. Both linkage orientation and linker
      length were found to affect in vitro antibacterial potency. The V-V series
      displayed the greatest potency against vancomycin-susceptible organisms and
      vancomycin-resistant Enterococcus faecalis (VRE) of VanB phenotype, while the C
      C, C-V, and V-R series displayed the most promising broad-spectrum activity that
      included VRE of VanA phenotype. Dimers bearing the shortest linkers were in all
      cases preferred for activity against VRE. The effects of linkage orientation and
      linker length on in vitro potency were not uniform; for example, (1) no single
      compound displayed activity that was superior against all test organisms to that
      of vancomycin or the other dimers, (2) linker length effects varied with test
      organism, and (3) whereas one-half of the dimers were more potent than vancomycin
      against methicillin-susceptible Staphylococcus aureus (MSSA), only one dimer was
      more potent against methicillin-resistant S. aureus (MRSA) and glycopeptide
      intermediate susceptible S. aureus (GISA). In interpreting the results, we have
      considered the potential roles of multivalency and of other phenomena.

PMID- 12785794
TI  - Spin-forbidden deprotonation of aqueous nitroxyl (HNO).
AB  - The first mechanistic study of a spin-forbidden proton-transfer reaction in
      aqueous solution is reported. Laser flash photolysis of alkaline trioxodinitrate
      (N(2)O(3)(2)(-), Angeli's anion) is used to generate a nitroxyl anion in its
      excited singlet state ((1)NO(-)). Through rapid partitioning between protonation
      by water and electronic relaxation, (1)NO(-) produces (1)HNO (ground state, yield
      96%) and (3)NO(-) (ground state, yield 4%), which comprise a unique conjugate
      acid-base couple with different ground-state multiplicities. Using the large
      difference between reactivities of (1)HNO and (3)NO(-) in the peroxynitrite
      forming reaction with (3)O(2), the kinetics of spin-forbidden deprotonation
      reaction (1)HNO + OH(-) --> (3)NO(-) + H(2)O is investigated in H(2)O and D(2)O.
      Consistent with proton transfer, this reaction exhibits primary kinetic hydrogen
      isotope effect k(H)/k(D) = 3.1 at 298 K, which is found to be temperature
      dependent. Arrhenius pre-exponential factors and activation energies of the
      second-order rate constant are found to be: log(A, M(-)(1) s(-)(1)) = 10.0 +/-
      0.2 and E(a) = 30.0 +/- 1.1 kJ/mol for proton transfer and log(A, M(-)(1) s(
      )(1)) = 10.4 +/- 0.1 and E(a) = 35.1 +/- 0.7 kJ/mol for deuteron transfer.
      Collectively, these data are interpreted to show that the nuclear reorganization
      requirements arising from the spin prohibition necessitate significant activation
      before spin change can take place, but the spin change itself must occur
      extremely rapidly. It is concluded that a synergy between the spin prohibition
      and the reaction energetics creates an intersystem barrier and is responsible for
      slowness of the spin-forbidden deprotonation of (1)HNO by OH(-); the spin
      prohibition alone plays a minor role.

PMID- 12785795
TI  - Multigram scale synthesis and characterization of monodisperse tetragonal
      zirconia nanocrystals.
AB  - A new and simple method has been developed to synthesize large quantities of
      highly monodisperse tetragonal zirconia nanocrystals. In this synthesis, a
      nonhydrolytic sol-gel reaction between zirconium(IV) isopropoxide and
      zirconium(IV) chloride at 340 degrees C generated 4 nm sized zirconia
      nanoparticles. A high-resolution transmission electron microscopic (HRTEM) image
      showed that the particles have a uniform particle size distribution and that they
      are highly crystalline. These monodisperse nanoparticles were synthesized without
      any size selection process. X-ray diffraction studies combined with Rietveld
      refinement revealed that the ZrO(2) nanocrystals are the high-temperature
      tetragonal phase, and very close to a cubic phase. When zirconium(IV) bromide is
      used as a precursor instead of zirconium chloride, zirconia nanoparticles with an
      average size of 2.9 nm were obtained. The UV-visible absorption spectrum of 4 nm
      sized zirconia nanoparticles exhibited a strong absorption starting at around 270
      nm. A fluorescence spectrum with excitation at 300 nm showed a broad fluorescence
      band centered around 370 nm. FTIR spectra showed indication of TOPO binding on
      the ZrO(2) nanoparticle surface. These optical studies also suggest that the
      nanoparticles are of high quality in terms of narrow particle size distribution
      and relatively low density of surface trap states.

PMID- 12785796
TI  - Surface treatment of silicon carbide using TiO2(IV) photocatalyst.
AB  - Silicon carbide (SiC) and diamond were decomposed to CO(2)(g) by the
      photocatalysis with TiO(2) at room temperature, although the decomposition rate
      of diamond was very slow. According to the XPS spectra of Si2p on the SiC
      surface, SiO(2) was simultaneously formed on the surface by the TiO(2)
      photocatalysis. The thickness of the SiO(2) formed on the SiC surface during the
      photocatalytic oxidation for 1 h was estimated to be about 40 A from the depth
      profile of the XPS spectra using Ar etching. The SiC surface was oxidized by the
      TiO(2) photocatalysis even under the condition without a direct contact with the
      TiO(2). This indicates that the photocatalytic oxidation of the SiC occurs due to
      active oxygen species photogenerated on the TiO(2) surface, but not by hole
      produced in the valence band of the TiO(2). Moreover, a remote surface treatment
      system using the quartz beads coated with TiO(2) was developed for the SiC
      surface oxidation. Consequently, the TiO(2) photocatalysis will be very useful
      for the surface treatment of SiC such as photopatterning without defects and
      damage to the substrate because the photocatalytic reaction is carried out under
      mild conditions.

PMID- 12785797
TI  - Using spin dynamics of covalently linked radical ion pairs to probe the impact of
      structural and energetic changes on charge recombination.
AB  - We have synthesized a series of structurally related, covalently linked electron
      donor-acceptor triads having highly restricted conformations to study the effects
      of radical ion pair (RP) structure, energetics, and solvation on charge
      recombination. The chromophoric electron acceptor in these triads is a 4
      aminonaphthalene-1,8-dicarboximide (6ANI), in which the 4-amine nitrogen atom is
      part of a piperazine ring. The second nitrogen atom of the piperazine ring is
      part of a para-substituted aniline donor, where the para substituents are X = H,
      OMe, and NMe(2). The imide group of 6ANI is linked to a naphthalene-1,8:4,5
      bis(dicarboximide) (NI) electron acceptor across a phenyl spacer in a meta
      relationship. The triads undergo two-step photoinduced electron transfer to yield
      their respective XAn(*)(+)-6ANI-Ph-NI(*)(-) RP states, which undergo radical pair
      intersystem crossing followed by charge recombination to yield (3)NI. Time
      resolved electron paramagnetic resonance experiments on the spin-polarized RPs
      and triplet states carried out in toluene and in E-7, a mixture of nematic liquid
      crystals (LCs), show that for all three triads, the XAn(*)(+)-6ANI-Ph-NI(*)(-)
      RPs are correlated radical pairs and directly yield values of the spin-spin
      exchange interaction, J, and the dipolar interaction, D. The values of J are all
      about -1 mT and show that the LC environment most likely enforces the chair
      conformation at the piperazine ring, for which the RP distance is larger than
      that for the corresponding boat conformation. The values of D yield effective RP
      distances that agree well with those calculated earlier from the spin
      distributions of the radical ions. Within the LC, changing the temperature shows
      that the CR mechanism can be changed significantly as the energy levels of the
      RPs change relative to that of the recombination triplet.

PMID- 12785798
TI  - Non-arrhenius behavior in the unfolding of a short, hydrophobic alpha-helix.
      Complementarity of molecular dynamics and lattice model simulations.
AB  - The unfolding of the last, C-terminal residue of AcNH(2)-(l-Leu)(11)-NHMe in its
      alpha-helical form has been investigated by measuring the variation of free
      energy involved in the alpha(R) to beta conformational transition. These
      calculations were performed using large-scale molecular dynamics simulations in
      conjunction with the umbrella sampling method. For different temperatures ranging
      from 280 to 370 K, the free energy of activation was estimated. Concurrently,
      unfolding simulations of a homopolypeptide formed by twelve hydrophobic residues
      were carried out, employing a three-dimensional lattice model description of the
      peptide, with a temperature-dependent interaction potential. Using a Monte Carlo
      approach, the lowest free energy conformation, an analogue of a right-handed
      alpha-helix, was determined in the region where the peptide chain is well
      ordered. The free energy barrier separating this state from a distinct, compact
      conformation, analogue to a beta-strand, was determined over a large enough range
      of temperatures. The results of these molecular dynamics and lattice model
      simulations are consistent and indicate that the kinetics of the unfolding of a
      hydrophobic peptide exhibits a non-Arrhenius behavior closely related to the
      temperature dependence of the hydrophobic effect. These results further
      illuminate the necessity to include a temperature dependence in potential energy
      functions designed for coarse-grained models of proteins.

PMID- 12785799
TI  - Infrared spectra of group 14 hydrides in solid hydrogen: experimental observation
      of PbH4, Pb2H2, and Pb2H4.
AB  - Laser-ablated Si, Ge, Sn, and Pb atoms have been co-deposited with pure hydrogen
      at 3.5 K to form the group 14 hydrides. The initial SiH(2) product reacts
      completely to SiH(4), whereas substantial proportions of GeH(2), SnH(2), and
      PbH(2) are trapped in solid hydrogen. Further hydrogen atom reactions form the
      trihydride radicals and tetrahydrides of Ge, Sn, and Pb. The observation of
      PbH(4) at 1815 cm(-)(1) and PbD(4) at 1302 cm(-)(1) is in agreement with the
      prediction of quantum chemical calculations for these unstable tetrahydride
      analogues of methane. In addition, new absorptions are observed for Pb(2)H(2) and
      Pb(2)H(4), which have dibridged structures based on quantum chemical
      calculations.

PMID- 12785800
TI  - Characteristics of a miniature compartment-less glucose-O2 biofuel cell and its
      operation in a living plant.
AB  - We report the temperature, pH, glucose concentration, NaCl concentration, and
      operating atmosphere dependence of the power output of a compartment-less
      miniature glucose-O(2) biofuel cell, comprised only of two bioelectrocatalyst
      coated carbon fibers, each of 7 micro m diameter and 2 cm length (Mano, N.; Mao,
      F.; Heller, A. J. Am. Chem. Soc. 2002, 124, 12962). The bioelectrocatalyst of the
      anode consists of glucose oxidase from Aspergillus niger electrically "wired" by
      polymer I, having a redox potential of -0.19 V vs Ag/AgCl. That of the cathode
      consists of bilirubin oxidase from Trachyderma tsunodae "wired" by polymer II
      having a redox potential of +0.36 V vs Ag/AgCl (Mano, N.; Kim, H.-H.; Zhang, Y.;
      Heller, A. J. Am. Chem. Soc. 2002, 124, 6480. Mano, N.; Kim, H.-H.; Heller, A. J.
      Phys. Chem. B 2002, 106, 8842). Implantation of the fibers in the grape leads to
      an operating biofuel cell producing 2.4 micro W at 0.52 V.

PMID- 12785803
TI  - Bulk microphase segregation of an asymmetric organometallic-inorganic diblock
      copolymer: a remarkable example of concentric cylinders.
AB  - We report that an asymmetric diblock copolymer, poly(ferrocenyldimethylsilane-b
      dimethylsiloxane) (PFS90-b-PDMS900, PDI = 1.01, volume fraction PFS = 0.20), self
      assembles in the bulk state to form a hexagonal periodic structure with a
      remarkable morphology. Part of the major component forms the core of concentric
      cylinders with a mean diameter of 35.5 nm surrounded by a 7 nm thick shell of
      PFS. The remaining PDMS fills the interstitial spaces. The morphology was
      elucidated by small-angle X-ray scattering, as well as by scanning and
      conventional transmission electron microscopy.

PMID- 12785804
TI  - A chemical trick: how to make a digermene from a disilene, formation of 3delta
      1,2,3,4-disiladigermetene.
AB  - The unexpected reaction of tetrakis[di-tert-butyl(methyl)silyl]disilagermirenes
      (1a and 1b) with GeCl2.dioxane results in the quantitative formation of trans-1,2
      dichloro-1,2,3,4-tetrakis[di-tert-butyl(methyl)silyl]-3Delta-1,2,3,4
      disiladigermetene, 2, representing the first cyclotetrametallene containing two
      different heavier group 14 elements and the first digermene incorporated in a
      four-membered ring. trans-1,2-Dichloro-1,2,3,4-tetrakis[di-tert
      butyl(methyl)silyl]-3Delta-1,2,3,4-disilagermastannetene (8), with a Ge=Sn double
      bond, was also prepared by the reaction of 1 with SnCl2.dioxane. The crystal
      structure of 2 was established by X-ray crystallography, which showed a folded
      four-membered ring skeleton with a long Ge=Ge double bond (2.2911(4) A). The
      structural peculiarities of 2, as well as the possible mechanism of its
      formation, are also discussed.

PMID- 12785805
TI  - Interlocked chiral nanotubes assembled from quintuple helices.
AB  - Homochiral helical chains were rationally synthesized from C2-symmetric 1,1
      binaphthyl-6,6'-bipyridine ligands and linear metal-connecting points, Ni(acac)2.
      Five such homochiral helices associate in parallel to form nanotubes of 2 x 2 nm
      in dimensions which further intertwine to form periodically ordered, interlocked
      nanotubular architectures that possess nanometer-scale open channels and have
      high affinity for aromatic molecules. Chiral crown ethers have also been
      successfully incorporated into the walls of these nanotubes, which promises to
      lead to novel chiral zeolitic materials applicable in enantioselective processes.

PMID- 12785806
TI  - Validation of a model for the complex of HIV-1 reverse transcriptase with
      nonnucleoside inhibitor TMC125.
AB  - The structure for the complex of nonnucleoside inhibitor TMC125 and HIV-1 reverse
      transcriptase has been determined and validated through computation of resistance
      profiles using Monte Carlo/free-energy perturbation calculations. The good
      quantitative agreement between the computed and experimental anti-HIV activities
      for TMC125, nevirapine, and efavirenz with wild-type RT and four common mutants
      (L100I, K103N, Y181C, and Y188L) confirms the correctness of the predicted
      structure and provides insights into the improved potency of this novel NNRTI.
      The blue shading in the figure indicates basic residues.

PMID- 12785807
TI  - [3 + 2] Annulation of allylic silanes in acyclic stereocontrol: total synthesis
      of (9S)-dihydroerythronolide A.
AB  - The [3 + 2] annulation reactions of allylic silanes can be utilized to achieve
      acyclic stereocontrol. This method was employed as a key step in an
      enantioselective total synthesis of (9S)-dihydroerythronolide A. The key
      annulation reaction served to establish most of the stereochemistry of the
      target, including the two tetrasubstituted carbon stereocenters. The symmetry of
      the target molecule allowed it to be disconnected into two equally sized
      fragments, both of which were generated from the same annulation reaction. The
      two fragments were coupled using a tin(II)-mediated chelation-controlled aldol
      reaction of an alpha-benzyloxy ethyl ketone. This convergent total synthesis of
      (9S)-dihydroerythronolide A was accomplished with the longest linear sequence of
      29 steps and in 5.4% overall yield.

PMID- 12785808
TI  - Reversible, electrochemical interconversion of NADH and NAD+ by the catalytic
      (Ilambda) subcomplex of mitochondrial NADH:ubiquinone oxidoreductase (complex I).
AB  - NADH:ubiquinone oxidoreductase (complex I) is the first enzyme of the
      mitochondrial electron transport chain and catalyzes the oxidation of beta-NADH
      by ubiquinone, coupled to transmembrane proton translocation. It contains a
      flavin mononucleotide (FMN) at the active site for NADH oxidation, up to eight
      iron-sulfur (FeS) clusters, and at least one ubiquinone binding site. Little is
      known about the mechanism of coupled electron-proton transfer in complex I. This
      communication demonstrates how the catalytic fragment of complex I, subcomplex
      Ilambda, can be adsorbed onto a pyrolytic graphite edge electrode to catalyze the
      interconversion of NADH and NAD+, with the electrode as the electron acceptor or
      donor. NADH oxidation and NAD+ reduction are completely reversible and occur
      without the application of an overpotential. The potential of zero current
      denotes the potential of the NAD+/NADH redox couple, and the dependence of ENAD+
      on pH, and on the NADH:NAD+ ratio, is in accordance with the Nernst equation. The
      catalytic potential of the enzyme, Ecat, is close to one of the two reduction
      potentials of the active site FMN and to the potential of a nearby [2Fe - 2S]
      cluster; therefore, either one or both of these redox couples is suggested to be
      important in controlling NADH oxidation by complex I.

PMID- 12785810
TI  - Templated assembly of sulfide nanoclusters into cubic-C3N4 type framework.
AB  - Here we report a new type of nanocluster superlattice in which each four
      connected cluster ([M4In16S31],6- M = Fe, Co, Zn, and Cd) alternates with a three
      connected sulfur anion (S2-) to form a rare and yet theoretically important non
      centrosymmetric and non-interpenetrating (3,4)-connected net topologically
      identical to that of the hypothetical cubic carbon nitride type net. These
      materials have a ring size consisting of 16 tetrahedral atoms. Because of the
      large cluster size and the elimination of structural intergrowth, the volume
      fraction of the inorganic framework is as low as 38%. A strong photoluminescent
      emission has also been observed.

PMID- 12785809
TI  - A free, tricoordinate stannylium cation.
AB  - Tris(2,4,6-triisopropylphenyl)stannylium tetrakis(pentafluorophenyl)borate
      constitutes a free, tricoordinate tin cation according to its X-ray structure.
      There is no coordination between the cation and either solvent or anion, and
      there are no atoms at apical positions. DFT calculations confirm the structure
      and indicate that there is no agostic bonding between the ortho isopropyl
      methinyl hydrogens and the Sn atom. Calculation of the 119Sn chemical shift is in
      good agreement with the observed value.

PMID- 12785811
TI  - (C5M2-n)(n-) (M = Li, Na, K, and n = 0, 1, 2). A new family of molecules
      containing planar tetracoordinate carbons.
AB  - By highly correlated ab initio methods and DFT calculations, we have shown that
      alkaline metals can stabilize planar tetracoordinate carbon-containing molecules
      with the C(C4) skeleton. This family of molecules is C5M2, where M is an alkaline
      metal. The stability of these compounds is rationalized in terms of the
      delocalization of the p-orbital perpendicular to the molecular plane, the global
      hardness, and the electrophilicity. The analysis of several molecular scalar
      fields shows that the bonding between the C52- dianion and the metals is strongly
      ionic. The structures reported are the first examples with a planar
      tetracoordinate carbon, surrounded by carbon atoms, and stabilized, only, by
      electronic factors.

PMID- 12785812
TI  - Copper(I) and copper(II) complexes possessing cross-linked imidazole-phenol
      ligands: structures and dioxygen reactivity.
AB  - Catalytic reduction of O2 to H2O, and coupling to membrane proton translocation,
      occurs at the heterobinuclear heme a3-CuB active site of cytochrome c oxidase.
      One of the CuB ligated histidines is cross-linked to a neighboring tyrosine (C-N
      bond; tyrosine C6 and histidine epsilon-nitrogen), and the protic residue of this
      cross-linked His-Tyr moiety is proposed to participate as both an electron and a
      proton donor in the catalytic dioxygen reduction event. To provide insight into
      the chemistry of such a moiety, we have synthesized and characterized tetra- and
      tridentate pyridylalkylamine chelate ligands {LN4OR and LN3OR (R = H or Me)},
      which include an imidazole-phenol (or anisole) cross-link and their copper(I/II)
      complexes. [CuI(LN4OH)]B(C6F5)4 (1) reacts with dioxygen at -80 degrees C in THF,
      forming an unstable trans-mu-1,2-peroxodicopper(II)complex, which subsequently
      converts to a dimeric copper(II)-phenolate complex [{Cu(LN4O-)}2](B(C6F5)4)2
      (5a). The close analogue [CuI(LN4OMe)]B(C6F5)4 (3) binds dioxygen reversibly at 
      80 degrees C in tetrahydrofuran. Stopped-flow kinetics of the reaction
      [CuI(LN3OH)]ClO4 (2) with O2 in CH2Cl2 indicate a steady formation of the purple
      dimeric product [{Cu(LN3O-)}2](ClO4)2 (5b), which has been analyzed in the
      temperature range from -40 to +20 degrees C, DeltaH = -9.6 (6) kJ mol-1, DeltaS =
      -168 (2) J mol-1 K-1 (k(-40 degrees C) = 1.05(4) x 106 and k(+20 degrees C) =
      4.6(2) x 105 M-2 s-1). The X-ray crystal structures of 1,
      [CuII(LN3OH)(MeOH)(OClO3-)](ClO4) (4), 5a, and 5b are reported.

PMID- 12785813
TI  - Cruciform pi-systems for molecular electronics applications.
AB  - This study details a modular and general synthesis of a new class of molecules
      consisting of cruciform pi-systems. The key to synthesizing these molecules was
      an unprecedented double Staudinger cyclization. Once formed, these rigid
      compounds assemble into ordered monolayer films on metal and metal oxide surfaces
      to orient their conjugated, bis-phenyloxazole subunits upright. This surface
      orientation is enforced by the external phenyl substituents that are out of the
      ring plane, thus preventing the prone conformation.

PMID- 12785814
TI  - Dynamic NMR line-shape analysis demonstrates that the villin headpiece subdomain
      folds on the microsecond time scale.
AB  - There is considerable interest in small proteins that fold very rapidly. These
      proteins have become attractive targets for both theoretical and computational
      studies. The independently folded 36-residue villin headpiece subdomain has been
      the subject of a number of such studies and is predicted to fold quickly. We
      demonstrate using dynamic NMR line-shape analysis that the protein folds on the
      time scale of 10 mus. Folding rates were directly estimated between 56 and 78
      degrees C using resolved protein resonances from three different residues at both
      500 and 700 MHz. The rates estimated using different residues and different field
      strengths agree well with each other. The estimated folding rate lies between 0.5
      and 2.0 x 105 s-1 over this temperature range. The folding rate depends only
      weakly on temperature.

PMID- 12785815
TI  - Generation of phosphoranes derived from phosphites. A new class of phosphorus
      ylides leading to high E selectivity with semi-stabilizing groups in Wittig
      olefinations.
AB  - Tosylhydrazones derived from aryl aldehydes react with t-BuOK, ClFeTPP, (MeO)3P,
      and aldehydes to furnish olefins with high E selectivity. These reactions occur
      through a Wittig-type pathway via the corresponding diazo compounds, metal
      carbenes and phosphorous ylides, with the water-soluble trimethyl phosphate as
      the byproduct. Similar reactions can also be performed using ethyl diazoacetate;
      however, high E selectivity was only observed in the presence of LiBr. In this
      case, the reaction is believed to occur via the phosphonate anion, formed through
      an Arbuzov reaction. Thus this olefination reaction occurs through a Horner
      Wadsworth-Emmons (HWE) reaction but the phosphonate anion is generated under
      completely base-free conditions.

PMID- 12785816
TI  - Pressure-induced hydration at 0.6 GPa in a synthetic gallosilicate zeolite.
AB  - The onset of pressure-induced hydration and volume expansion is lowered to 0.6
      GPa via the increased flexibility of the host lattice using isomorphous
      substitution of Al by larger Ga in a sodium aluminosilicate natrolite.

PMID- 12785817
TI  - Catalytic enantioselective synthesis of alpha-aminooxy and alpha-hydroxy ketone
      using nitrosobenzene.
AB  - The highly enantioselective and O-selective nitroso aldol reaction of tin
      enolates 2 and nitrosobenzene (1) has been developed with the use of (R)-BINAP
      silver complexes as a catalyst. After the various silver salts were surveyed, the
      AgOTf and the AgClO4 complex were found to be optimal in the O-selective nitroso
      aldol reaction in both asymmetric induction (up to 97% ee) and regioselection
      (O/N = >99/1), affording aminooxy ketone 3. The product 3 can be transformed to
      alpha-hydroxy ketone 5 without any loss of enantioselectivity. Thus, the method
      provides an efficient approach to the catalytic enantioselective introduction of
      oxygen alpha- to the carbonyl group.

PMID- 12785818
TI  - Total synthesis of the salicylate enamide macrolide oximidine II.
AB  - The asymmetric synthesis of the salicylate enamide macrolide oximidine II is
      reported. The synthesis involves a highly regio- and stereoselective ring-closing
      metathesis of a bis-diene substrate to construct the macrocyclic triene core.
      Copper(I)-mediated amidation of a (Z)-vinyl iodide was employed to attach the
      enamide side chain.

PMID- 12785819
TI  - The total synthesis of (+)-migrastatin.
AB  - The first total synthesis of (+)-migrastatin, a macrolide natural product with
      interesting antimetastatic properties, has been accomplished. Our concise and
      flexible approach utilizes a Lewis acid-catalyzed diene aldehyde condensation to
      install the three contiguous stereocenters and the trisubstituted (Z)-alkene of
      migrastatin. Construction of the two remaining stereocenters and incorporation of
      the glutarimide-containing side chain have been achieved via an anti-selective
      aldol reaction, followed by a Horner-Wadsworth-Emmons olefination. Finally, the
      assembly of the macrocycle has been realized by a highly (E)-selective ring
      closing metathesis.

PMID- 12785820
TI  - ZSM-5 monolith of uniform mesoporous channels.
AB  - A ZSM-5 monolith of uniform mesopores(meso-ZSM-5) was synthesized with the
      template method using carbon aerogel of uniform mesopores of great pore volume.
      The pore size distribution determined by N2 adsorption showed the presence of
      mesopores with an average pore width of 11 nm and micropores with an average pore
      width of 0.51 nm. Field emission scanning electron micrograph observation
      revealed the presence of uniform mesopores. X-ray diffraction and FT-IR provided
      evidence that the synthesized meso-ZSM-5 monolith has a highly crystalline ZSM-5
      structure.

PMID- 12785821
TI  - The first Suzuki cross-couplings of aryltrimethylammonium salts.
AB  - The first Suzuki cross-coupling reaction of aryltrimethylammonium triflates based
      on the use of an IMes.Ni(0) catalyst system is described. A wide range of
      electron-withdrawing and electron-donating substituents are tolerated on both the
      aryltrimethylammonium triflate and the boronic acid components of this reaction.
      In addition to arylboronic acids, the scope of the reaction is extended to
      encompass both boronate esters and alkenylboranes. This methodology constitutes a
      novel, mild method to activate anilines for metal-catalyzed cross-coupling
      reactions.

PMID- 12785822
TI  - Infrared measurements and calculations on H2O.HO.
AB  - We have measured the infrared spectrum of H2O.HO in argon matrices at 11.5 +/-
      0.5 K. We have also calculated the vibrational frequencies and intensities of the
      H2O.HO complex. As a result of these measurements and calculations, we have
      assigned a previously unassigned absorption band at 3442.1 cm-1 to the OH stretch
      in the radical complexed to the water molecule. This absorption originates from a
      complex that is situated in a different site within the argon matrix to those
      absorptions already assigned to this vibration at 3452.2 and 3428.0 cm-1. We
      observe a decrease in intensity of the OH radical stretching vibration of the
      H2O.HO complex upon isotopic substitution of D for H that agrees well with our
      calculations.

PMID- 12785823
TI  - Inorganic electride: theoretical study on structural and electronic properties.
AB  - We report self-consistent ab initio calculations of structural and electronic
      properties for a kind of recently synthesized inorganic electride. The optimized
      geometry gives zigzag cesium chains within the sinusoidal channels of the
      zeolite. Among the wide energy gap of the zeolite, near the conduction bands,
      there are two interstitial electride bands mainly contributed by 6s electrons of
      Cs atoms, which have a delocalized real space distribution along the channels.
      For all different doping rates studied, we find that a finite density of states
      appears at the Fermi level, which predicts a metallic behavior of this material.
      Detailed electronic structure reveals all the essential properties of the
      electride model. The shift of Fermi level and the delocalization of the highest
      occupied bands cause this material to be a powerful reducing agent.

PMID- 12785824
TI  - A terminal and four-coordinate titanium alkylidene prepared by oxidatively
      induced alpha-hydrogen abstraction.
AB  - One-electron oxidation of the beta-diketiminate titanium(III) bis-neopentyl
      complex (Nacnac)Ti(CH2tBu)2 (Nacnac = [Ar]NC(Me)CHC(Me)N[Ar], Ar = 2,6
      (CHMe2)2C6H3) promotes alpha-abstraction to afford the rare and terminal four
      coordinate neopentylidene (Nacnac)Ti=CHtBu(OTf), which was structurally
      characterized. Alkylidene (Nacnac)Ti=CHtBu(OTf) reacts cleanly with benzophenone
      and the imine functionality of the Nacnac ligand to afford the corresponding
      Wittig-type products.

PMID- 12785825
TI  - The first conjugate addition reaction of terminal alkynes catalytic in copper:
      conjugate addition of alkynes in water.
AB  - We document that alkynyl copper reagents generated under aqueous conditions from
      terminal acetylenes, catalytic Cu(OAc)2, and sodium ascorbate undergo additions
      to Meldrum's acid-derived Michael acceptors at room temperature (Scheme 1). The
      additions are not only novel, but also constitute the first example of the
      conjugate addition reaction of an acetylide catalytic in copper.

PMID- 12785826
TI  - Carbon-carbon bond formation in palladium(II)-catalyzed allylic oxidation: a
      novel oxidative carbocyclization of allene-substituted olefins.
AB  - A new efficient palladium(II)-catalyzed oxidative carbocyclization has been
      developed. It was found that allene-substituted olefins 1 cyclized in the
      presence of 1 mol % Pd(O2CCF3)2 and p-benzoquinone (2 equiv) to give bicyclic
      ring systems 2 in good to excellent yields. The cyclization constitutes a new
      type of carbon-carbon bond forming reaction between an allene and an olefin under
      oxidative conditions.

PMID- 12785827
TI  - Efficient and rapid C-Si bond cleavage in supercritical water.
AB  - Arylsilanes, alkenylsilanes, allylic silanes, and alkylsilanes were found to
      undergo extremely facile and rapid C-Si bond cleavage in supercritical water. The
      rapid C-Si bond cleavage occurred even with robust unactivated tetraalkylsilanes.
      The control experiments revealed the dramatic difference between supercritical
      and subcritical conditions and that between supercritical water and supercritical
      methanol, attesting to a unique reactivity of supercritical water in C-Si bond
      cleavage.

PMID- 12785828
TI  - Ruthenium-catalyzed carbon-carbon bond formation between propargylic alcohols and
      alkenes via the allenylidene-ene reaction.
AB  - A novel ruthenium-catalyzed carbon-carbon bond formation between propargylic
      alcohols and alkenes via the allenylidene-ene reaction has been found to afford
      the corresponding 2,4-disubstituted-1-hexen-5-ynes in moderate yields. The
      finding described here discloses a new reactivity of allenylidene complexes. As a
      synthetic application, intramolecular cyclization of propargylic alcohols bearing
      an alkene moiety has been developed to give the corresponding syn-substituted
      chromanes in high yields with an excellent diastereoselectivity.

PMID- 12785830
TI  - Kinetic isotope effects implicate two electrophilic oxidants in cytochrome p450
      catalyzed hydroxylations.
AB  - Intramolecular kinetic isotope effects (KIEs) were determined for cytochrome P450
      catalyzed hydroxylation reactions of methyl-dideuterated trans-2
      phenylcyclopropylmethane-d2 (1-d2), which gives two products from oxidation of
      the methyl group, trans-2-phenylcyclopropylmethanol (2) and 1-phenyl-3-buten-1ol
      (3). In oxidations of each enantiomer of 1-d2 with three P450 enzymes (CYP2B1,
      CYPDelta2E1, and CYPDelta2E1 T303A), the apparent intramolecular KIEs were
      different for products 2 and 3 in all cases and different for each enzyme
      substrate combination. In oxidations of each enantiomer of undeuterated 1-d0 and
      trideuteriomethyl 1-d3 by CYP2B1 and CYPDelta2E1, the ratio of products 2/3
      decreased for 1-d3 in comparison to 1-d0 in all cases. The results require
      multiple pathways for P450-catalyzed hydroxylation and are consistent with the
      "two-oxidants" model, where hydroxylation is effected by both the hydroperoxy
      iron species and the iron-oxo species. The results are not consistent with
      predictions of the "two-states" model for P450-catalyzed hydroxylations, where
      oxidations occur from a low-spin state and a high-spin state of iron-oxo.

PMID- 12785831
TI  - Palladium-catalyzed deracemization of allylic carbonates in water with formation
      of allylic alcohols: hydrogen carbonate ion as nucleophile in the palladium
      catalyzed allylic substitution and kinetic resolution.
AB  - The palladium-catalyzed deracemization of racemic cyclic and acyclic allylic
      methyl carbonates in water in the presence of N,N'-(1R,2R)-1,2
      cyclohexanediylbis[2-(diphenylphophino)benzamide] proceeds with high
      enantioselectivities to give the corresponding allylic alcohols in high yields.
      This deracemization involves a palladium-catalyzed allylic substitution with the
      in-situ-formed hydrogen carbonate ion and an irreversible decomposition of the
      intermediate allylic hydrogen carbonates, with formation of the corresponding
      allylic alcohols. The palladium-catalyzed reaction of racemic cyclic allylic
      acetates with potassium hydrogen carbonate in water in the presence of the chiral
      bisphosphane proceeds with a highly selective kinetic resolution to give the
      corresponding allylic alcohols and allylic acetates.

PMID- 12785829
TI  - A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne
      antitumor antibiotic C-1027 biosynthesis.
AB  - The C-1027 enediyne antibiotic contains an unusual 3-chloro-4,5-dihydroxy-beta
      phenylalanine moiety that is thought to be derived from tyrosine by an
      aminomutase reaction. However, none of the genes identified within the C-1027
      gene cluster encode proteins with strong homology to known aminomutases. The
      sgcC4 gene encodes a protein with strong homology to dehydroalanine-dependent
      histidine/phenylalanine ammonia lyases. The sgcC4 gene was expressed in E. coli,
      and overproduced SgcC4 was purified as a His6-tagged fusion protein. Biochemical
      characterization of the purified SgcC4 establishes that SgcC4 is an aminomutase
      that catalyzes the conversion of l-tyrosine to (S)-beta-tyrosine and employs 4
      methylideneimidazole-5-one (MIO) at its active site. The latter was supported by
      borohydride and cyanide inhibition studies and confirmed by site-directed
      mutagenesis. The S153A mutant exhibited a 340-fold decrease in kcat/KM. SgcC4
      represents a novel type of aminomutase, extending the known MIO chemistry from
      ammonia lyases into aminomutases.

PMID- 12785833
TI  - Hemoglobin dendrimers: functional protein clusters.
AB  - A cluster of cross-linked hemoglobin tetramers was prepared by conjugating active
      esters to amino groups of a starburst dendrimer. Comparison of oxygen-binding
      properties of the protein cluster to those of nonclustered species reveals an
      increase in affinity and a decrease in cooperativity in the cluster. The altered
      oxygen-binding properties are assigned to protein-protein interactions.

PMID- 12785834
TI  - Supramolecular interactions between fullerenes and porphyrins.
AB  - Perdew-Burke-Ernzerhof density functional theory calculations have been carried
      out to investigate the host-guest interactions for several fullerene-porphyrin
      supramolecular complexes. The nature of the interactions has been discussed. The
      fullerene-porphyrin interaction energies for the complexes studied are found to
      be in the range from -16 to -18 kcal/mol.

PMID- 12785832
TI  - Surface-localized release of nitric oxide via sol-gel chemistry.
AB  - The release of nitric oxide (NO) from polymers has proven to be highly effective
      at inhibiting platelet adhesion and thus enhancing the blood compatibility of
      medical implants. Micropatterning techniques were used to design surfaces that
      release NO while preserving the underlying substrate for other applications
      (e.g., sensors). Micropatterned NO-releasing substrates based on aminosilane
      containing methyltrimethoxysilane sol-gels were prepared and characterized in
      terms of stability, NO surface flux, and resistance to in vitro platelet
      adhesion. We have found that surface-localized NO release from substrates
      modified with sol-gel micropatterns exhibit enhanced blood compatibility relative
      to controls.

PMID- 12785835
TI  - Titanium alkoxide complex of functionalized conjugated dienes. A versatile bis
      anionic template for stereoselective construction of carbon frameworks.
AB  - 1,3-Butadiene-2-carboxylates were treated with a titanium(II) alkoxide reagent,
      Ti(O-i-Pr)4/2i-PrMgCl, to generate diene-titanium alkoxide complexes, the
      presence of which was verified by hydrolysis and deuteriolysis to give the
      corresponding monoolefins or their bis-deuterated counterpart. These diene
      complexes underwent successive addition to an aldehyde (as the first
      electrophile) and iodine (as the second one) in a highly regio- and
      stereoselective manner to give the corresponding iodo alcohol. Optically active
      1,3-butadiene-2-carboxylates afforded the same adducts of high asymmetric
      induction. Besides these electron-deficient dienes, electron-rich 2-siloxy-1,3
      butadienes also participated in the formation of the titanium complex, which led
      to the preparation of functionalized enol silyl ethers through regio- and
      stereoselective coupling with carbonyl compounds and hydrolytic workup.

PMID- 12785836
TI  - A mild C-O bond formation catalyzed by a rhenium-oxo complex.
AB  - A mild method for the regioselective synthesis of propargyl ethers by the
      coupling of propargyl alcohols with a range of other alcohols is described. The
      method employs an air- and moisture-tolerant rhenium-oxo complex ((dppm)ReOCl3)
      as a catalyst for the formation of sp3-carbon-oxygen bonds without the need for
      prior activation of the propargyl alcohol or deprotonation of the alcohol
      nucleophile. A broad range of functional groups is tolerated, including aryl
      halides, olefins, esters, and acid-labile functional groups such as acetals.
      Furthermore, displacement of the alcohol occurs preferentially even in the
      presence of other electrophiles such as primary alkyl halides and conjugated
      esters.

PMID- 12785837
TI  - Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor
      for assembly of [2Fe-2S] clusters in ISU-type proteins.
AB  - ISU (eukaryotes) and IscU (prokaryotes) are a homologous family of proteins that
      appear to provide a platform for assembly of [2Fe-2S] centers prior to delivery
      to an apo target protein. The intermediate [2Fe-2S] ISU-bound cluster is formed
      by delivery of iron and sulfur to the apo ISU, with the latter delivered through
      an IscS-mediated reaction. The identity of the iron donor has thus far not been
      established. In this paper we demonstrate human frataxin to bind from six to
      seven iron ions. Iron binding to frataxin has been quantitated by iron-dependent
      fluorescence measurements [K(D)(Fe(3+)) approximately 11.7 microM; (K(D)(Fe(2+))
      approximately 55.0 microM] and isothermal titration calorimetry (ITC)
      [K(D)(Fe(3+)) approximately 10.2 microM]. Enthalpies and entropies for ferric ion
      binding were determined from calorimetric measurements. Both fluorescence (K(D)
      0.45 microM) and ITC measurements (K(D) 0.15 microM) demonstrate holo frataxin to
      form a complex with ISU with sub-micromolar binding affinities. Significantly,
      apo frataxin does not bind to ISU, suggesting an important role for iron in cross
      linking the two proteins and/or stabilizing the structure of frataxin that is
      recognized by ISU. Holo frataxin is also shown to mediate the transfer of iron
      from holo frataxin to nucleation sites for [2Fe-2S] cluster formation on ISU. We
      have demonstrated elsewhere [J. Am. Chem. Soc. 2002, 124, 8774-8775] that this
      iron-bound form of ISU is viable for assembly of holo ISU, either by subsequent
      addition of sulfide or by NifS-mediated sulfur delivery. Provision of holo
      frataxin and inorganic sulfide is sufficient for cluster assembly in up to 70%
      yield. With NifS as a sulfur donor, yields in excess of 70% of holo ISU were
      obtained. Both UV-vis and CD spectroscopic characteristics were found to be
      consistent with those of previously characterized ISU proteins. The time course
      for cluster assembly was monitored from the 456 nm absorbance of holo ISU formed
      during the [2Fe-2S] cluster assembly reaction. A kinetic rate constant k(obs)
      approximately 0.075 min(-)(1) was determined with 100 microM ISU, 2.4 mM Na(2)S,
      and 40 microM holo frataxin in 50 mM Tris-HCl (pH 7.5) with 4.3 mM DTT. Similar
      rates were obtained for NifS-mediated sulfur delivery, consistent with iron
      release from frataxin as a rate-limiting step in the cluster assembly reaction.

PMID- 12785838
TI  - Cross-reactive arrays based on three-way junctions.
AB  - We report herein a novel system for the parallel processing of molecular
      recognition events utilizing arrays of oligonucleotide-based fluorescent sensors
      to characterize hydrophobic molecules in solution. The binding domains of the
      sensors were based on three-way junctions that utilize double helical stems as
      framework regions to reliably fold regardless of variations in or around the
      binding domain. A reporting domain was introduced by the specific substitution of
      a single phosphodiester group with a phosphorothioate, followed by selective
      functionalization with a fluorophore. The sensors were organized into cross
      reactive arrays to yield characteristic fingerprints for samples containing
      hydrophobic molecules. The fingerprints can be used to characterize steroids in
      solution, including complex biologically important fluids. Arrays have the
      potential for clinical applications such as the detection of gross errors in
      steroidogenesis.

PMID- 12785840
TI  - Base sequence effects in radical cation migration in duplex DNA: support for the
      polaron-like hopping model.
AB  - A series of anthraquinone-linked (AQ) duplex DNA oligomers were prepared and
      investigated. Irradiation of the AQ injects a radical cation into the DNA. The
      radical cation migrates through the DNA and reacts selectively at GG steps, which
      leads to strand cleavage after treatment with piperidine. The oligomers
      investigated in this work were selected to assess the effect on long-distance
      charge transport of placing a T base (or bases) in a strand of repeating purine
      bases. With notable exceptions, the amount of strand scission decreases with the
      distance between the AQ and the GG step. The results are consistent only with
      models for long-distance transport, such as thermally activated polaron-like
      hopping, that incorporate radical cation delocalization over two or more adjacent
      bases.

PMID- 12785839
TI  - NMR studies of DNA single strands and DNA:RNA hybrids with and without 1
      propynylation at C5 of oligopyrimidines.
AB  - The 1-propynylation at C5 of consecutive pyrimidines in DNA can enhance DNA:RNA
      hybrid stability at 37 degrees C by over 1 kcal/mol of substitution [Barnes, T.
      W., III; Turner, D. H. J. Am. Chem. Soc.2001, 123, 4107-4118]. To provide
      information on the structural consequences of propynylation, two-dimensional NMR
      spectroscopy was used to study the structures of several oligonucleotides.
      Intraresidue nuclear Overhauser effect spectroscopy cross peaks were observed at
      30 degrees C and a 200 ms mixing time in the H6-H1' region for
      5'(dC(P)C(P)U(P)C(P)C(P)U(P)U(P)) (ssPrODN) but not for 5'(dCCUCCUU) (ssODN),
      suggesting preorganization of the propynylated single strand. NMR structures of
      the duplexes 5'(dC(P)C(P)U(P)C(P)C(P)U(P)U(P))3':3'(rGAGGAGGAAAU)5' (PrODN:RNA),
      5'(dCC(P)U(P)C(P)C(P)U(P)U(P))3':3'(rGAGGAGGAAAU)5' (sPrODN1:RNA), and
      5'(dCCUCCUU)3':3'(rGAGGAGGAAAU)5' (ODN:RNA) indicate that their global structures
      are almost identical. The NMR data, however, suggest that the 5'-end of
      sPrODN1:RNA is more dynamic than that of PrODN:RNA. In the propynylated duplexes,
      the propyne group stacks on the aromatic ring of the 5'-base and extends into the
      major groove. The results suggest that the increased stability of the
      propynylated duplexes is caused by preorganization of the propynylated single
      strand and different interactions in the double strand. The propynyl group
      provides volume exclusion, enhanced stacking, and possibly different solvation.

PMID- 12785841
TI  - Synthesis and biological evaluation of Rhizobium sin-1 lipid A derivatives.
AB  - A highly convergent strategy for the synthesis of several derivatives of the
      lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced
      intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido
      beta-d-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1-thio-alpha-d-glucopyranoside
      (5), which is protected in such a way that the anomeric center, the C-2 and C-2'
      amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized.
      The synthetic strategy was used for the preparation of 2-deoxy-6-O-[2-deoxy-3-O
      [(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d
      glucopyranosyl]-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]
      alpha-d-glucopyranose (11) and 2-deoxy-6-O-[2-deoxy-3-O-[(R)-3-hydroxy
      hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d-glucopyranosyl]-2
      [(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-d-glucono-1,5
      lactone (13), which contain an unusual octacosanoic acid moiety and differ in the
      oxidation state of the anomeric center. The results of biological studies
      indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli
      lipopolysaccharides (LPS). Furthermore, 13 emulated the ability of heterogeneous
      R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role
      of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic
      effect. Compound 13 is the first example of a lipid A derivative that is devoid
      of phosphate but possesses antagonistic properties, making it an attractive lead
      compound for development of a drug to use in the treatment of Gram-negative
      septicemia.

PMID- 12785842
TI  - Synthesis and characterization of model compounds of the lysine tyrosyl quinone
      cofactor of lysyl oxidase.
AB  - 4-n-Butylamino-5-ethyl-1,2-benzoquinone (1(ox)) has been synthesized as a model
      compound for the LTQ (lysine tyrosyl quinone) cofactor of lysyl oxidase (LOX). At
      pH 7, 1(ox) has a lambda(max) at 504 nm and exists as a neutral o-quinone in
      contrast to a TPQ (2,4,5-trihydroxyphenylalanine quinone) model compound, 4,
      which is a resonance-stabilized monoanion. Despite these structural differences
      1(ox) and 4 have the same redox potential (ca. -180 mV vs SCE). The structure of
      the phenylhydrazine adduct of 1(ox) (2) is reported, and 2D NMR spectroscopy has
      been used to show that the position of nucleophilic addition is at C(1). UV-vis
      spectroscopic pH titration of phenylhydrazine adducts of 1(ox) and 4, 2, and 11,
      respectively, reveals a similar red shift in lambda(max) at alkaline pH with the
      same pK(a) (approximately 11.8). In contrast, the red shift in lambda(max) at
      acidic pH conditions yields different pK(a) values (2.12 for 2 vs -0.28 for 11),
      providing a means to distinguish LTQ from TPQ. Reactions between in situ
      generated 4-ethyl-1,2-benzoquinone and primary amines give a mixture of products,
      indicating that the protein environment must play an essential role in LTQ
      biogenesis by directing the nucleophilic addition of the epsilon-amino group of a
      lysine residue to the C(4) position of a putative dopaquinone intermediate.
      Characterization of a 1,6-adduct between an o-quinone and butylamine (3-n
      butylamino-5-ethyl-1,2-benzoquinone, 13) confirms the assignment of LTQ as a 1,4
      addition product.

PMID- 12785843
TI  - Reverse proteolysis promoted by in situ generated peptide ester fragments.
AB  - In this contribution we describe a general synthesis concept for the in situ
      preparation of protease specific reactants using methyl thioesters as universal
      precursors. The precursor esters are readily available by standard synthesis
      procedures and can be used directly as reactants for protease-mediated peptide
      coupling reactions. Alternatively, they can serve as initial building blocks for
      the in situ preparation of various types of substrate mimetics. The synthesis of
      the latter is achieved by a one-pot spontaneous transthioesterification reaction
      of the parent thioester (Y-(Xaa)(n)-SMe-->Y-(Xaa)(n)-SR; R: CH(2)CH(2)COOH,
      CH(2)C(6)H(5), C(6)H(4)NHC(:NH)NH(2)), which proceeds efficiently in both a
      sequential manner and parallel to the subsequent enzymatic reaction. The
      resulting substrate mimetics act as efficient acyl donor components and show the
      typical behavior of substrate mimicry enabling irreversible reactions with
      originally nonspecific acyl moieties. Neither a workup of the substrate mimetic
      intermediate nor changes of the reaction conditions during the whole synthesis
      process are required. Model peptide syntheses using trypsin, alpha-chymotrypsin,
      and V8 protease as the biocatalysts proved the function of the approach and
      illustrated its synthetic value for protease-mediated reactions and the
      compatibility of the approach with state-of-the-art solid-phase peptide ester
      synthesis methods.

PMID- 12785844
TI  - The effect of minor-groove hydrogen-bond acceptors and donors on the stability
      and replication of four unnatural base pairs.
AB  - The stability and replication of DNA containing self-pairs formed between
      unnatural nucleotides bearing benzofuran, benzothiophene, indole, and
      benzotriazole nucleobases are reported. These nucleobase analogues are based on a
      similar scaffold but have different hydrogen-bond donor/acceptor groups that are
      expected to be oriented in the duplex minor groove. The unnatural base pairs do
      not appear to induce major structural distortions and are accommodated within the
      constraints of a B-form duplex. The differences between these unnatural base
      pairs are manifest only in the polymerase-mediated extension step, not in base
      pair stability or synthesis. The benzotriazole self-pair is extended with an
      efficiency that is only 200-fold less than a correct natural base pair. The data
      are discussed in terms of available polymerase crystal structures and imply that
      further modifications may result in unnatural base pairs that can be both
      efficiently synthesized and extended, resulting in an expanded genetic alphabet.

PMID- 12785845
TI  - Surface plasmon resonance imaging studies of protein-carbohydrate interactions.
AB  - Carbohydrate arrays fabricated on gold films were used to study carbohydrate
      protein interactions with surface plasmon resonance (SPR) imaging. An
      immobilization scheme consisting of the formation of a surface disulfide bond was
      used to attach thiol-modified carbohydrates onto gold films and to fabricate
      carbohydrate arrays. The carbohydrate attachment steps were characterized using
      polarization modulation Fourier transform infrared reflection absorption
      spectroscopy; and poly(dimethylsiloxane) microchannels were used to immobilize
      probe compounds at discrete locations on a gold film. The binding of the
      carbohydrate-binding proteins concanavalin A (ConA) and jacalin to arrays
      composed of the monosaccharides mannose and galactose was monitored with SPR
      imaging. SPR imaging measurements were employed to accomplish the following: (i)
      construct adsorption isotherms for the interactions of ConA and jacalin to the
      carbohydrate surfaces, (ii) monitor protein binding to surfaces presenting
      different compositions of the immobilized carbohydrates, and (iii) measure the
      solution equilibrium dissociation constants for ConA and jacalin toward mannose
      and galactose, respectively. Adsorption coefficients (K(ADS)) of 2.2 +/- 0.8 x
      10(7) M(-)(1) and 5.6 +/- 1.7 x 10(6) M(-)(1) were obtained for jacalin adsorbing
      to a galactose surface and ConA adsorbing to a mannose surface, respectively. The
      solution equilibrium dissociation (K(D)) constant for the interaction of jacalin
      and galactose was found to be 16 +/- 5 microM, and for ConA and mannose was found
      to be 200 +/- 50 microM.

PMID- 12785846
TI  - Chemoselective ligation applied to the synthesis of a biantennary N-linked
      glycoform of CD52.
AB  - We report here a strategy for the synthesis of N-linked glycopeptide analogues
      that replace the glycosidic linkages extending from the core pentasaccharide with
      thioethers amenable to construction by chemoselective ligation. The key building
      block, a pentasaccharide-Asn analogue containing two thiol residues, was
      incorporated into CD52 by 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase
      peptide synthesis. An undecasaccharide mimetic was then readily generated by
      alkylation of this glycopeptide with an N-bromoacetamido trisaccharide. The rapid
      assembly of a complex type N-linked glycopeptide mimetic was accomplished using
      this technique.

PMID- 12785847
TI  - Synthesis, structural characterization, and immunological properties of carbon
      nanotubes functionalized with peptides.
AB  - Carbon nanotubes (NTs) are becoming highly attractive molecules for applications
      in medicinal chemistry. The main problem of insolubility in aqueous media has
      been solved by developing a synthetic protocol that allows highly water-soluble
      carbon NTs to be obtained. As a result, biologically active peptides can be
      easily linked through a stable covalent bond to carbon NTs. We have demonstrated
      that a bound peptide from the foot-and-mouth disease virus, corresponding to the
      141-159 region of the viral envelope protein VP1, retained the structural
      integrity and was recognized by monoclonal and polyclonal antibodies. In
      addition, this peptide-NT conjugate is immunogenic, eliciting antibody responses
      of the right specificity. Such a system could be greatly advantageous for
      diagnostic purposes and could find future applications in vaccine delivery.

PMID- 12785848
TI  - Rational design of a calcium-binding protein.
AB  - Calcium ions play key roles as structural components in biomineralization and as
      a second messenger in signaling pathways. We have introduced a de novo designed
      calcium-binding site into the framework of a non-calcium-binding protein, domain
      1 of CD2. The resulting protein selectively binds calcium over magnesium with
      calcium-binding affinity comparable to that of natural extracellular calcium
      binding proteins (K(d) of 50 microM). This experiment is the first successful
      metalloprotein design that has a high coordination number (seven) metal-binding
      site constructed into a beta-sheet protein. Our results demonstrate the
      feasibility of designing a single calcium-binding site into a host protein,
      taking into account only local properties of a calcium-binding site obtained by a
      survey of natural calcium-binding proteins and chelators. The resulting site
      exhibits strong metal selectivity, suggesting that it should now be feasible to
      understand and manipulate signaling processes by designing novel calcium
      modulated proteins with specifically desired functions and to affect their
      stability.

PMID- 12785849
TI  - Singlet molecular oxygen generated from lipid hydroperoxides by the russell
      mechanism: studies using 18(O)-labeled linoleic acid hydroperoxide and monomol
      light emission measurements.
AB  - The decomposition of lipid hydroperoxides into peroxyl radicals is a potential
      source of singlet oxygen ((1)O(2)) in biological systems. We report herein on
      evidence of the generation of (1)O(2) from lipid hydroperoxides involving a
      cyclic mechanism from a linear tetraoxide intermediate proposed by Russell. Using
      (18)O-labeled linoleic acid hydroperoxide (LA(18)O(18)OH) in the presence of
      Ce(4+) or Fe(2+), we observed the formation of (18)O-labeled (1)O(2)
      ((18)[(1)O(2)]) by chemical trapping of (1)O(2) with 9,10-diphenylanthracene
      (DPA) and detected the corresponding (18)O-labeled DPA endoperoxide
      (DPA(18)O(18)O) by high-performance liquid chromatography coupled to tandem mass
      spectrometry. Spectroscopic evidence for the generation of (1)O(2) was obtained
      by measuring (i) the dimol light emission in the red spectral region (lambda >
      570 nm); (ii) the monomol light emission in the near-infrared (IR) region (lambda
      = 1270 nm); and (iii) the quenching effect of sodium azide. Moreover, the
      presence of (1)O(2) was unequivocally demonstrated by the direct spectral
      characterization of the near-IR light emission. For the sake of comparison,
      (1)O(2) deriving from the H(2)O(2)/OCl(-) and H(2)O(2)/MoO(4)(2)(-) systems or
      from the thermolysis of the endoperoxide of 1,4-dimethylnaphthalene was also
      monitored. These chemical trapping and photoemission properties clearly
      demonstrate that the decomposition of LA(18)O(18)OH generates (18)[(1)O(2)],
      consistent with the Russell mechanism and pointing to the involvement of (1)O(2)
      in lipid hydroperoxide mediated cytotoxicity.

PMID- 12785850
TI  - A novel and rapid encoding method based on mass spectrometry for "one-bead-one
      compound" small molecule combinatorial libraries.
AB  - A novel and efficient encoding method based on mass spectrometry for "one-bead
      one-compound" small molecule combinatorial libraries has been developed. The
      topologically segregated bifunctional resin beads with orthogonal protecting
      groups in the outer and inner regions are first prepared according to our
      previously published procedure. Prior to library synthesis, the inner core of
      each bead is derivatized with 3-4 different coding blocks on a cleavable linker.
      Each functional group on the scaffold is encoded by an individual coding block
      containing a functional group with the same chemical reactivity. During the
      library synthesis, the same chemical reactions take place on the scaffold (outer
      layer of the bead) and coding blocks (inner core of the bead) concurrently. After
      screening, the coding tags in the positive beads are released, followed by
      molecular mass determination using matrix-assisted laser desorption ionization
      Fourier transform mass spectrometry. The chemical structure of library compounds
      can be readily identified according to the molecular masses of the coding tags.
      The feasibility and efficiency of this approach were demonstrated by the
      synthesis and screening of a model small molecule library containing 84 672
      member compounds, with a model receptor, streptavidin. Streptavidin binding
      ligands with structural similarity (17) were identified. The decoding results
      were clear and unambiguous.

PMID- 12785851
TI  - Protonation and reactivity towards carbon dioxide of the mononuclear tetrahedral
      zinc and cobalt hydroxide complexes, [Tp(Bu)t(,Me)]ZnOH and [Tp(Bu)t(,Me)]CoOH:
      comparison of the reactivity of the metal hydroxide function in synthetic
      analogues of carbonic anhydrase.
AB  - The tris(3-tert-butyl-5-methylpyrazolyl)hydroborato zinc hydroxide complex
      [Tp(Bu)t(,Me)]ZnOH is protonated by (C(6)F(5))(3)B(OH(2)) to yield the aqua
      derivative [[Tp(Bu)t(,Me)]Zn(OH(2))][HOB(C(6)F(5))(3)], which has been
      structurally characterized by X-ray diffraction, thereby demonstrating that
      protonation results in a lengthening of the Zn-O bond by ca. 0.1 A. The
      protonation is reversible, and treatment of [[Tp(Bu)t(,Me)]Zn(OH(2))](+) with
      Et(3)N regenerates [Tp(Bu)t(,Me)]ZnOH. Consistent with the notion that the
      catalytic hydration of CO(2) by carbonic anhydrase requires deprotonation of the
      coordinated water molecule, [[Tp(Bu)t(,Me)]Zn(OH(2))](+) is inert towards CO(2),
      whereas [Tp(Bu)t(,Me)]ZnOH is in rapid equilibrium with the bicarbonate complex
      [Tp(Bu)t(,Me)]ZnOC(O)OH under comparable conditions. The cobalt hydroxide complex
      [Tp(Bu)t(,Me)]CoOH is likewise protonated by (C(6)F(5))(3)B(OH(2)) to yield the
      aqua derivative [[Tp(Bu)t(,Me)]Co(OH(2))][HOB(C(6)F(5))(3)], which is
      isostructural with the zinc complex. The aqua complexes
      [[Tp(Bu)t(,Me)]M(OH(2))][HOB(C(6)F(5))(3)] (M = Zn, Co) exhibit a hydrogen
      bonding interaction between the metal aqua and boron hydroxide moieties. This
      hydrogen bonding interaction may be viewed as analogous to that between the aqua
      ligand and Thr-199 at the active site of carbonic anhydrase. In addition to the
      structural similarities between the zinc and cobalt complexes, [Tp(Bu)t(,Me)ZnOH]
      and [Tp(Bu)()t(,Me)]CoOH, and between [[Tp(Bu)t(,Me)]Zn(OH(2))](+) and
      [[Tp(Bu)t(,Me)]Co(OH(2))](+), DFT (B3LYP) calculations demonstrate that the pK(a)
      value of [[Tp]Zn(OH(2))](+) is similar to that of [[Tp]Co(OH(2))](+). These
      similarities are in accord with the observation that Co(II) is a successful
      substitute for Zn(II) in carbonic anhydrase. The cobalt hydroxide
      [Tp(Bu)()t(,Me)]CoOH reacts with CO(2) to give the bridging carbonate complex
      [[Tp(Bu)t(,Me)]Co](2)(mu-eta(1),eta(2)-CO(3)). The coordination mode of the
      carbonate ligand in this complex, which is bidentate to one cobalt center and
      unidentate to the other, is in contrast to that in the zinc counterpart
      [[Tp(Bu)t(,Me)]Zn](2)(mu-eta(1),eta(1)-CO(3)), which bridges in a unidentate
      manner to both zinc centers. This difference in coordination modes concurs with
      the suggestion that a possible reason for the lower activity of Co(II)-carbonic
      anhydrase is associated with enhanced bidentate coordination of bicarbonate
      inhibiting its displacement.

PMID- 12785852
TI  - Molecular recognition of alpha,beta-unsaturated carbonyl compounds using aluminum
      tris(2,6-diphenylphenoxide) (ATPH): structural and conformational analysis of
      ATPH complexes and application to the selective vinylogous aldol reaction.
AB  - Various alpha,beta-unsaturated carbonyl compounds were coordinated with aluminum
      tris(2,6-diphenylphenoxide) (ATPH) to give the corresponding Lewis acid-base
      complexes in a distinctive coordination fashion (selective coordination). ATPH
      recognizes carbonyl substrates and subsequently orients itself as it forms a
      stable complex through selective coordination with the carbonyl oxygen. Selective
      coordination also confers a conformational preference to each carbonyl compound
      under the steric and electronic influence of ATPH, which enables the vinylogous
      aldol reaction of alpha,beta-unsaturated carbonyl compounds to give the
      corresponding gamma-aldol products with different regio- and stereoselectivities.

PMID- 12785853
TI  - Bicarbonate surfoxidants: micellar oxidations of aryl sulfides with bicarbonate
      activated hydrogen peroxide.
AB  - The mechanism and kinetics of bicarbonate-catalyzed oxidations of sulfides by
      H(2)O(2) at the aqueous /cationic micellar interface have been investigated. The
      general term surfoxidant is introduced to describe the combination of an ionic
      surfactant with a reactive counterion that is itself an oxidant or activates an
      oxidant from the bulk solution to form an oxidant counterion. It is shown that
      the new catalytic cationic surfoxidant CTAHCO(3) (cetyltrimethylammonium
      bicarbonate) significantly enhances the overall oxidation rates as compared to
      the addition of bicarbonate salts to CTACl and CTABr, for which the halide
      counterions must undergo equilibrium displacement by the oxidant anion
      (peroxymonocarbonate, HCO(4)(-)). General equations based on the classic
      pseudophase model have been derived to account for the preequilibrium reaction in
      the aqueous and micellar phases, and the resulting model can be used to describe
      any micellar reaction with associated preequilibria. Rate constants and relevant
      equilibrium constants for HCO(4)(-) oxidations of aryl sulfides at micellar
      surfaces have been estimated for CTAHCO(3), CTACl, and CTABr. The second-order
      rate constants in the Stern layer (k(2)(m)) for sulfide oxidations by HCO(4)(-)
      are estimated to be approximately 50-fold (PhSEtOH) and approximately 180-fold
      (PhSEt) greater than the background rate constant k(m)(0) for oxidation by
      H(2)O(2) at the micellar surface. The estimated values of k(2)(m) are lower than
      the corresponding values in water by a factor of 20-70 depending on the
      substrate, but the high local concentration of the bicarbonate activator in the
      surfoxidant and the local accumulation of substrate as a result of strong binding
      to the micelle lead to a net increase in the observed reaction rates. Comparisons
      of CTAHCO(3)-activated peroxide to other highly reactive oxidants such as
      peroxymonosulfate (HSO(5)(-)) in aqueous surfactant media suggest a wide variety
      of potential applications for this green oxidant.

PMID- 12785854
TI  - Spectroscopic investigations of bis(sulfoximine) copper(II) complexes and their
      relevance in asymmetric catalysis.
AB  - The structure of Cu(II) complex 3 formed within the course of a stereoselective
      Diels-Alder reaction was investigated by EXAFS, CW-EPR at X- and W-band, HYSCORE,
      pulsed ENDOR, and UV-vis spectroscopy. The experimental techniques indicate that
      the chiral bis(sulfoximine) ligand (S,S)-1 and the dienophile form a tetragonally
      distorted complex in CH(2)Cl(2). The ligand binds to the Cu(II) center via the
      imine nitrogens, whereas the dienophile interacts via the carbonyl oxygen atoms.
      The additional sites of the first coordination sphere are occupied by counterions
      and, presumably, solvent molecules. At the axial position, a triflate anion binds
      via an oxygen atom.

PMID- 12785855
TI  - Synthesis, structures, and conformational characteristics of calixarene
      monoanions and dianions.
AB  - The synthesis, complete characterization, and solid state structural and solution
      conformation determination of calix[n]arenes (n = 4, 6, 8) is reported. A
      complete series of X-ray structures of the alkali metal salts of calix[4]arene
      (HC4) illustrate the great influence of the alkali metal ion on the solid state
      structure of calixanions (e.g., the Li salt of monoanionic HC4 is a monomer; the
      Na salt of monoanionic HC4 forms a dimer; and the K, Rb, and Cs salts exist in
      polymeric forms). Solution NMR spectra of alkali metal salts of monoanionic
      calix[4]arenes indicate that they have the cone conformation in solution.
      Variable-temperature NMR spectra of salts HC4.M (M = Li, Na, K, Rb, Cs) show that
      they possess similar coalescence temperatures, all higher than that of HC4. Due
      to steric hindrance from tert-butyl groups in the para position of p-tert
      butylcalix[4]arene (Bu(t)C4), the alkali metal salts of monoanionic Bu(t)C4 exist
      in monomeric or dimeric form in the solid state. Calix[6]arene (HC6) and p-tert
      butylcalix[6]arene (Bu(t)C6) were treated with a 2:1 molar ratio of M(2)CO(3) (M
      = K, Rb, Cs) or a 1:1 molar ratio of MOC(CH(3))(3) (M = Li, Na) to give
      calix[6]arene monoanions, but calix[6]arenes react in a 1:1 molar ratio with
      M(2)CO(3) (M = K, Rb, Cs) to afford calix[6]arene dianions. Calix[8]arene (HC8)
      and p-tert-butylcalix[8]arene (Bu(t)()C8) have similar reactivity. The alkali
      metal salts of monoanionic calix[6]arenes are more conformationally flexible than
      the alkali metal salts of dianionic calix[6]arenes, which has been shown by their
      solution NMR spectra. X-ray crystal structures of HC6.Li and HC6.Cs indicate that
      the size of the alkali metal has some influence on the conformation of
      calixanions; for example, HC6.Li has a cone-like conformation, and HC6.Cs has a
      1,2,3-alternate conformation. The calix[6]arene dianions show roughly the same
      structural architecture, and the salts tend to form polymeric chains. For most
      calixarene salts cation-pi arene interactions were observed.

PMID- 12785856
TI  - Asymmetric environments in encapsulation complexes.
AB  - Symmetrical, self-assembled capsules capable of surrounding two guests offer a
      new approach to enantioselection through coencapsulation: when one guest is
      chiral, the space remaining is also chiral. This notion is explored within a
      cylindrical capsule. The dimensions of the capsule select appropriately sized
      combinations of guests, the shape of the capsule prevents tumbling of rigid
      molecules, and the chemical surface of the capsule orients polar functions
      within. Chiral carboxylic acids such as mandelic acid and alpha-Br-butyric acid
      are identified as promising compounds for this purpose, but diastereoselection is
      modest (<25% de).

PMID- 12785857
TI  - Dendrimer-tuned formation of luminescent organic microcrystals.
AB  - Microcrystals of an organic fluorescent dye, 4-n-octylamino-7-nitrobenz-2-oxa-1,3
      diazole (NBD-C8), were prepared by reprecipitation in water. The crystallization
      kinetics was monitored by UV/vis absorption spectroscopy, and a model was
      proposed. The size and shape of the microcrystals were analyzed by laser light
      scattering, fluorescence microscopy, and scanning electron microscopy. In the
      presence of PAMAM dendrimers of generation 2.5, 3.5, and 4.5, the crystallization
      process was drastically accelerated. The crystals obtained were smaller and more
      regular than those formed in pure water and were not agglomerated. There are
      probably two levels of interaction of NBD-C8 with the dendrimers, which act as
      both templates and colloid stabilizers.

PMID- 12785858
TI  - Using soluble polymers in latent biphasic systems.
AB  - A new strategy for carrying out reactions with a soluble polymer-bound reagent or
      catalyst is described. In this latent biphasic process, a solvent mixture at the
      cusp of immiscibility is prepared and used to carry out a reaction under
      homogeneous conditions. Then, after the reaction is complete, this mixture is
      perturbed by the addition of solvent or some other perturbing agent to produce a
      biphasic mixture. The product-containing phase is then separated under
      liquid/liquid conditions from the polymer-containing phase. The generality of
      this process is demonstrated using both dye-labeled polymers as surrogates for
      polymer-bound catalysts and with various polymer-bound organic and transition
      metal catalysts or reagents. In cases where a polymeric catalyst is used, the
      addition of fresh solvent and substrate reforms the original mixture allowing
      facile reuse of the catalyst.

PMID- 12785859
TI  - Catalytic asymmetric synthesis of quaternary carbons bearing two aryl
      substituents. Enantioselective synthesis of 3-alkyl-3-aryl oxindoles by catalytic
      asymmetric intramolecular heck reactions.
AB  - A practical sequence involving three consecutive palladium(0)-catalyzed reactions
      has been developed for synthesizing 3-alkyl-3-aryloxindoles in high
      enantiopurity. The Heck cyclization precursors 10 and 11a-k are generated in one
      step by chemoselective Stille cross-coupling of 2'-triflato-(Z)-2-stannyl-2
      butenanilide 9 with aryl or heteroaryl iodides. The pivotal catalytic asymmetric
      Heck cyclization step of this sequence takes place in high yield and with high
      enantioselectivity (71-98% ee) with the Pd-BINAP catalyst derived from Pd(OAc)(2)
      to construct oxindoles containing a diaryl-substituted all-carbon quaternary
      carbon center. A wide variety of aryl and heteroaryl substituents, including ones
      of considerable steric bulk, can be introduced at C3 of oxindoles in this way
      (Table 4). The only limitations encountered to date are aryl substituents
      containing ortho nitro or basic amine functionalities and the bulky N-alkyl-7
      oxindolyl group. Asymmetric Heck cyclization of butenalide 22 having an o-(N
      acetyl-N-benzylamino)phenyl substituent at C2 provided a approximately 1:1
      mixture of amide atropisomers 23 and 24 in high yield and high
      enantioselectivity. These atropisomers are formed directly upon Heck cyclization
      of 22 at 80 degrees C, as they interconvert thermally to only a small extent at
      this temperature.

PMID- 12785860
TI  - Stability of thin-film solid-state electroluminescent devices based on tris(2,2'
      bipyridine)ruthenium(II) complexes.
AB  - The factors affecting the operating life of the light-emitting electrochemical
      cells (LECs) based on films of tris(2,2'-bipyridine)ruthenium(II) both in
      sandwich (using an ITO anode and a Ga:Sn cathode) and planar (using
      interdigitated electrode arrays (IDAs)) configurations were investigated.
      Stability of these devices is greatly improved when they are produced and
      operated under drybox conditions. The proposed mechanism of the LEC degradation
      involves formation of a quencher in a small fraction of tris(2,2'
      bipyridine)ruthenium(II) film adjacent to the cathode, where light generation
      occurs, as follows from the observed electroluminescence profile in the LECs
      constructed on IDAs, showing that the charge injection in such devices is highly
      asymmetric, favoring hole injection. Bis(2,2'-bipyridine)diaquoruthenium(II) is
      presumed to be the quencher responsible for the device degradation. A microscopic
      study of photo- and electroluminescence profiles of planar light-emitting
      electrochemical cells was shown as a useful approach for studies of charge
      carrier injection into organic films.

PMID- 12785861
TI  - Three dimensional architectures of ultra-high density semiconducting nanowires
      deposited on chip.
AB  - We report a "clean" and fast process, utilizing supercritical carbon dioxide, for
      producing ultrahigh densities, up to 10(12) nanowires per square centimeter, of
      ordered germanium nanowires on silicon and quartz substrates. Uniform mesoporous
      thin films were employed as templates for the nucleation and growth of
      unidirectional nanowire arrays orientated almost perpendicular to a substrate
      surface. Additionally, these nanocomposite materials display room-temperature
      photoluminescence (PL), the energy of which is dependent on the diameter of the
      encased nanowires. The ability to synthesis ultrahigh-density arrays of
      semiconducting nanowires on-chip is a key step in future "bottom-up" fabrication
      of multilayered device architectures for nanoelectronic and optoelectronic
      devices.

PMID- 12785862
TI  - Theoretical and experimental consideration of the reactions between VxOy+ and
      ethylene.
AB  - We present joint theoretical and experimental results which provide evidence for
      the selectivity of V(x)O(y)(+) clusters in reactions toward ethylene due to the
      charge and different oxidation states of vanadium for different cluster sizes.
      Density functional calculations were performed on the reactions between
      V(x)O(y)(+) and ethylene, allowing us to identify the structure-reactivity
      relationship and to corroborate the experimental results obtained by Castleman
      and co-workers (Zemski, K. A.; Justes, D. R.; Castleman, A. W., Jr. J. Phys.
      Chem. A 2001, 105, 10237). The lowest-energy structures for the V(2)O(2)(-)(6)(+)
      and V(4)O(8)(-)(10)(+) clusters and the V(2)O(3)(-)(6)(+)-C(2)H(4) and
      V(4)O(10)(+)-C(2)H(4) complexes, as well as the energetics for reactions between
      ethylene and V(2)O(4)(-)(6)(+) and V(4)O(10)(+) are presented here. The oxygen
      transfer reaction pathway was determined to be the most energetically favorable
      one available to V(2)O(5)(+) and V(4)O(10)(+) via a radical-cation mechanism. The
      association and replacement reaction pathways were found to be the optimal
      channels for V(2)O(4)(+) and V(2)O(6)(+), respectively. These results are in
      agreement with the experimental results reported previously. Experiments were
      also conducted for the reactions between V(2)O(5)(+) and ethylene to include an
      energetic analysis at increasing pressures. It was found that the addition of
      energy depleted the production of V(2)O(4)(+), confirming that a more involved
      reaction rather than a collisional process is responsible for the observed
      phenomenon. In this contribution we show that investigation of reactions
      involving gas-phase cationic vanadium oxide clusters with small hydrocarbons is
      suitable for the identification of reactive centers responsible for selectivity
      in heterogeneous catalysis.

PMID- 12785863
TI  - Temperature dependence of the distribution of the first passage time: results
      from discontinuous molecular dynamics simulations of an all-atom model of the
      second beta-hairpin fragment of protein G.
AB  - More than 22 000 folding kinetic simulations were performed to study the
      temperature dependence of the distribution of first passage time (FPT) for the
      folding of an all-atom Go-like model of the second beta-hairpin fragment of
      protein G. We find that the mean FPT (MFPT) for folding has a U (or V)-shaped
      dependence on the temperature with a minimum at a characteristic optimal folding
      temperature T(opt). The optimal folding temperature T(opt) is located between the
      thermodynamic folding transition temperature and the solidification temperature
      based on the Lindemann criterion for the solid. Both the T(opt) and the MFPT
      decrease when the energy bias gap against nonnative contacts increases. The high
      order moments are nearly constant when the temperature is higher than T(opt) and
      start to diverge when the temperature is lower than T(opt). The distribution of
      FPT is close to a log-normal-like distribution at T > or = T(opt). At even lower
      temperatures, the distribution starts to develop long power-law-like tails,
      indicating the non-self-averaging intermittent behavior of the folding dynamics.
      It is demonstrated that the distribution of FPT can also be calculated reliably
      from the derivative of the fraction not folded (or fraction folded), a measurable
      quantity by routine ensemble-averaged experimental techniques at dilute protein
      concentrations.

PMID- 12785864
TI  - Standing wave enhancement of red absorbance and photocurrent in dye-sensitized
      titanium dioxide photoelectrodes coupled to photonic crystals.
AB  - The light harvesting efficiency of dye-sensitized photoelectrodes was enhanced by
      coupling a TiO(2) photonic crystal layer to a conventional film of TiO(2)
      nanoparticles. In addition to acting as a dielectric mirror, the inverse opal
      photonic crystal caused a significant change in dye absorbance which depended on
      the position of the stop band. Absorbance was suppressed at wavelengths shorter
      than the stop band maximum and was enhanced at longer wavelengths. This effect
      arises from the slow group velocity of light in the vicinity of the stop band,
      and the consequent localization of light intensity in the voids (to the blue) or
      in the dye-sensitized TiO(2) (to the red) portions of the photonic crystal. By
      coupling a photonic crystal to a film of TiO(2) nanoparticles, the short circuit
      photocurrent efficiency across the visible spectrum (400-750 nm) could be
      increased by about 26%, relative to an ordinary dye-sensitized nanocrystalline
      TiO(2) photoelectrode.

PMID- 12785865
TI  - Theoretical studies on the mechanism of inhibition of Ribonucleotide Reductase by
      (E)-2'-Fluoromethylene-2'-deoxycitidine-5'-diphosphate.
AB  - (E)-2'-Fluoromethylene-2'-deoxycitidine-5'-diphosphate (FMCDP) is a potent time
      dependent inactivator of the enzyme Ribonucleotide Reductase, which operates by
      destructing an essential tyrosil radical and performing a covalent addition to an
      active site residue. Considerable effort to elucidate the inhibition mechanism
      has been undertaken in recent years, and some insights have been obtained.
      Although a mechanistic proposal has been put forward, based on a general paradigm
      of inhibition of RNR by 2' substituted substrate analogues, details about the
      mechanism have remained elusive. Namely, the exact residue that adds to the
      inhibitor is still not identified, although mutagenesis experiments suggest that
      it should correspond to the E441 residue. In this work, we performed an extensive
      theoretical exploration of the potential energy surface of a model system
      representing the active site of RNR with FMCDP, using Density Functional Theory.
      This study establishes the detailed mechanism of inhibition, which is
      considerably different from the one proposed earlier. The proposed mechanism is
      fully consistent with available experimental data. Energetic results reveal
      unambiguously that the residue adding to the inhibitor is a cysteine, most
      probably C439, and exclude the possibility of the addition of E441. However, the
      E441 residue is shown to be essential for inhibition, catalyzing both the major
      and minor inhibition pathways, in agreement with mutagenesis results. It is shown
      also that the major mode of inactivation mimics the early stages of the natural
      substrate pathway.

PMID- 12785866
TI  - Modeling the polymorphism of pentacene.
AB  - Thin films of pentacene are known to crystallize in at least four different
      polymorphs. All polymorphs are layered structures that are characterized by their
      interlayer spacing d(001). We develop a model that rationalizes the size of the
      interlayer spacing in terms of intralayer shifts of the pentacene molecules along
      their long molecular axes. It explains the wide variety of interlayer spacings,
      without distorting the herringbone pattern that is characteristic of many acenes.
      Using two simple theoretical models, we attempt to relate the intralayer shifts
      with the dominant, although weak, interatomic interactions (van der Waals, weak
      electrostatic, and covalent). For two polymorphs, a consistent picture is found.
      A full understanding of the other two, substrate-induced, polymorphs probably
      requires consideration of interlayer interactions.

PMID- 12785867
TI  - 8-Oxoguanine enhances bending of DNA that favors binding to glycosylases.
AB  - Molecular dynamics (MD) simulations were carried out on the DNA oligonucleotide
      GGGAACAACTAG:CTAGTTGTTCCC in its native form and with guanine in the central
      G(19):C(6) base pair replaced by 8-oxoguanine (8oxoG). A box of explicit water
      molecules was used for solvation, and Na(+) counterions were added to neutralize
      the system. The direction and magnitude of global bending were assessed by a
      technique used previously to analyze simulations of DNA containing a thymine
      dimer. The presence of 8oxoG did not greatly affect the magnitude of DNA bending;
      however, bending into the major groove was significantly more probable when 8oxoG
      replaced G(19). Crystal structures of glycosylases bound to damaged-DNA
      substrates consistently show a sharp bend into the major groove at the damage
      site. We conclude that changes in bending dynamics that assist the formation of
      this kink are a part of the mechanism by which glycosylases of the base excision
      repair pathway recognize the presence of 8oxoG in DNA.

PMID- 12785870
TI  - Vaccination priorities in travel.

PMID- 12785871
TI  - Immunisation against hepatitis A, hepatitis B and typhoid fever via combined
      vaccination: rationale, immunogenicity and reactogenicity.

PMID- 12785872
TI  - Rapid hepatitis B immunisation for the traveller: comparison of two accelerated
      schedules with a 2-month schedule.

PMID- 12785873
TI  - Rapid protection against hepatitis A and B using an accelerated vaccination
      schedule: comparison of combined vaccine, Twinrix, with separate vaccines.

PMID- 12785874
TI  - Rapid protection and vaccination against hepatitis A for travellers.

PMID- 12785875
TI  - Current status and replies to frequently posed questions on atovaquone plus
      proguanil (Malarone) for the prevention of malaria.
AB  - Each year at least 30 000 Western travellers acquire malaria and approximately 1
      4% of those who acquire Plasmodium falciparum malaria will die as a result of
      infection. Almost all cases and fatalities are preventable with the use of
      measures to reduce mosquito bites and appropriate chemoprophylaxis for those at
      high risk of infection. There are currently a limited number of licensed drugs
      available to prevent malaria in travellers. New effective and well tolerated
      agents are urgently needed because of increasing resistance to antimalarials such
      as chloroquine and proguanil, and real and perceived intolerance to standard
      drugs such as mefloquine. A newly licensed antimalarial (atovaquone plus
      proguanil; Malarone) compares favourably with other drug options, although some
      prescribers may be unfamiliar with the specific advantages and disadvantages of
      this antimalarial. This article reviews recent clinical experience and randomised
      controlled trial data in order to address frequently asked questions about this
      new combination drug.

PMID- 12785876
TI  - Vortex phase diagram of F=1 spinor Bose-Einstein condensates.
AB  - We have calculated the F=1 ground state of a spinor Bose-Einstein condensate
      trapped harmonic potential with an applied Ioffe-Pitchard magnetic field. The
      vortex phase diagram is found in the plane spanned by perpendicular and
      longitudinal magnetic fields. The ferromagnetic condensate has two vortex phases
      which differ by winding number in the spinor components. The two vortices for the
      F(z)=-1 antiferromagnetic condensate are separated in space. Moreover, we
      considered an average local spin |<S-->>| to testify to what extent it is
      parallel to magnetic field (the nonadiabatic effects). We have shown that the
      effects are important at vortex cores.

PMID- 12785877
TI  - Rotating ground states of trapped atoms in a Bose-Einstein condensate with
      arbitrary two-body interactions.
AB  - In a k-dimensional system of weakly interacting Bose atoms trapped by a
      spherically symmetric and harmonic external potential, an exact expression is
      obtained for the rotating ground states at a fixed angular momentum. The result
      is valid for arbitrary interactions obeying minimal physical requirements.
      Depending on the sign of a modified scattering length, it reduces to either a
      collective rotation or a condensed vortex state, with no alternative. The ground
      state can undergo a kind of quantum phase transition when the shape of the
      interaction potential is smoothly varied.

PMID- 12785879
TI  - Test of cosmic spatial isotropy for polarized electrons using a rotatable torsion
      balance.
AB  - To test the cosmic spatial isotropy, we use a rotatable torsion balance carrying
      a transversely spin-polarized ferrimagnetic Dy6Fe23 mass. With a rotation period
      of 1 h, the period of anisotropy signal is reduced from one sidereal day by about
      24 times, and hence the 1/f noise is reduced. Our present experimental results
      constrain the cosmic anisotropy Hamiltonian H=C(1)sigma(1)+C2sigma(2)+C3sigma(3)
      (sigma(3) is in the axis of earth rotation) to (C(2)(1)+C(2)(2))(1/2)=(1.1+/
      2.0)x10(-20) eV and /C(3)/=(1.1+/-6.0)x10(-19) eV. This improves the previous
      limits on (C(2)(1)+C(2)(2))(1/2) by 27 times.

PMID- 12785878
TI  - Experimental observation of four-photon entanglement from parametric down
      conversion.
AB  - We observe polarization entanglement between four photons produced from a single
      down-conversion source. The nonclassical correlations between the measurement
      results violate a generalized Bell inequality for four qubits. The characteristic
      properties and its easy generation with high interferometric contrast make the
      observed four-photon state well suited for implementing advanced quantum
      communication schemes such as multiparty quantum key distribution, secret
      sharing, and telecloning.

PMID- 12785880
TI  - Traversable wormholes with arbitrarily small energy condition violations.
AB  - Traversable wormholes necessarily require violations of the averaged null energy
      condition, this being the definition of "exotic matter." However, the theorems
      which guarantee the energy condition violation are remarkably silent when it
      comes to making quantitative statements regarding the "total amount" of energy
      condition violating matter in the spacetime. We develop a suitable measure for
      quantifying this notion and demonstrate the existence of spacetime geometries
      containing traversable wormholes that are supported by arbitrarily small
      quantities of exotic matter.

PMID- 12785881
TI  - Neutrinos of energy approximately 10(16) eV from gamma-ray bursts in pulsar wind
      bubbles.
AB  - The supranova model for gamma-ray bursts (GRBs) is becoming increasingly more
      popular. In this scenario the GRB occurs weeks to years after a supernova
      explosion, and is located inside a pulsar wind bubble (PWB). Protons accelerated
      in the internal shocks that emit the GRB may interact with the external PWB
      photons producing pions which decay into approximately 10(16) eV neutrinos. A
      km(2) neutrino detector would observe several events per year correlated with the
      GRBs.

PMID- 12785882
TI  - Dynamical symmetry breaking of extended gauge symmetries.
AB  - We construct asymptotically free gauge theories exhibiting dynamical breaking of
      the left-right gauge group G(LR)=SU(3)(c) x SU(2)(L) x SU(2)(R) x U(1)(B-L), and
      its extension to the Pati-Salam gauge group G(422)=SU(4)(PS) x SU(2)(L) x
      SU(2)(R). The models incorporate technicolor for electroweak breaking, and
      extended technicolor for the breaking of G(LR) and G422 and the generation of
      fermion masses. They include a seesaw mechanism for neutrino masses, without a
      grand unified theory (GUT) scale. These models explain why G(LR) and G422 break
      to SU(3)(c) x SU(2)(L) x U(1)(Y), and why this takes place at a scale
      (approximately 10(3) TeV) large compared to the electroweak scale, but much
      smaller than a GUT scale.

PMID- 12785884
TI  - Search for time-reversal violation in the beta decay of polarized 8Li nuclei.
AB  - The transverse polarization of electrons emitted in the beta decay of polarized
      8Li nuclei has been measured. For the time-reversal violating triple correlation
      parameter we find R=(0.9+/-2.2)x10(-3). This result is in agreement with the
      standard model and yields improved constraints on exotic tensor contributions to
      the weak interaction. Combined with other experimental results and using a model
      for the coupling constants, a new limit for the mass of a possible scalar
      leptoquark, m(LQ)>560 GeV/c(2) (90% C.L.), is obtained.

PMID- 12785885
TI  - Parton coalescence and the antiproton/pion anomaly at RHIC.
AB  - Coalescence of minijet partons with partons from the quark-gluon plasma formed in
      relativistic heavy ion collisions is suggested as the mechanism for production of
      hadrons with intermediate transverse momentum. The resulting enhanced antiproton
      and pion yields at intermediate transverse momenta give a plausible explanation
      for the observed large antiproton to pion ratio. With further increasing
      momentum, the ratio is predicted to decrease and approach the small value given
      by independent fragmentations of minijet partons after their energy loss in the
      quark-gluon plasma.

PMID- 12785886
TI  - Hadronization in heavy-ion collisions: recombination and fragmentation of
      partons.
AB  - We argue that the emission of hadrons with transverse momentum up to about 5
      GeV/c in central relativistic heavy ion collisions is dominated by recombination,
      rather than fragmentation of partons. This mechanism provides a natural
      explanation for the observed constant baryon-to-meson ratio of about one and the
      apparent lack of a nuclear suppression of the baryon yield in this momentum
      range. Fragmentation becomes dominant at higher transverse momentum, but the
      transition point is delayed by the energy loss of fast partons in dense matter.

PMID- 12785883
TI  - Observation of B0-->pLambda(pi)(-).
AB  - We report the first observation of the charmless hyperonic B decay, B0-
      >pLambda(pi)(-), using a 78 fb(-1) data sample recorded on the Upsilon(4S)
      resonance with the Belle detector at KEKB. The measured branching fraction is
      B(B0-->pLambda(pi)(-))=(3.97(+1.00)(-0.80)+/-0.56)x10(-6). Searches for B0-
      >pLambda(K)- and pSigma(0)pi(-) yield no significant signals and we set 90%
      confidence-level upper limits of B(B0-->pLambda(K)-)<8.2x10(-7) and B(B0-
      >pSigma(0)pi(-))<3.8x10(-6).

PMID- 12785887
TI  - Excitation and decay of the isovector giant monopole resonances via the
      208Pb(3He,t p) reaction at 410 MeV.
AB  - The excitation and subsequent proton decay of the isovector spin-flip giant
      monopole resonance (IVSGMR) is studied via the 208Pb(3He,t) reaction at 410 MeV.
      In the inclusive spectrum (60+/-5)% of the non-energy-weighted sum-rule strength
      for this 2 variant Planck's over 2h omega resonance was found in the region
      29<Ex(208Bi)<51 MeV. The central excitation energy and width of the IVSGMR are
      37+/-1 MeV and 14+/-3 MeV, respectively. It is found that the branching ratio for
      proton decay is (52+/-12)% and that the deep neutron-hole states in 207Pb are
      strongly fed.

PMID- 12785888
TI  - Spin polarization of 37K produced in a single-proton pickup reaction at
      intermediate energies.
AB  - Spin polarization of 37K nuclei produced via single proton pickup from a 9Be
      target by a beam of 150 MeV/nucleon 36Ar has been observed. Positive spin
      polarization with magnitude (8.5+/-0.6)% was deduced near the peak of the 37K
      momentum distribution. The variation of the spin polarization as a function of
      outgoing 37K momentum is explained by a classical conservation model, as
      previously applied to describe the induced spin polarization observed for
      fragments produced in intermediate-energy heavy-ion reactions, with the condition
      that the picked-up proton has an average momentum equal to the Fermi momentum and
      is aligned along the incident beam direction.

PMID- 12785889
TI  - Alpha-particle production in the reaction 6Li+28Si at near-barrier energies.
AB  - The production of alpha particles in the 6Li+28Si reaction was studied at near
      barrier energies. Angular distributions were performed at four bombarding
      energies, namely, 7.5, 9, 11, and 13 MeV. The distributions were characterized by
      a Gaussian shape, which was integrated in order to obtain alpha-particle cross
      sections. Our results were compared with previous data of 6Li scattering on
      various heavier targets and found to exhibit a universal behavior. Present
      continuum-discretized-coupled-channel calculations support the obtained data. The
      consequences of the systematic behavior of the alpha-particle production on the
      unusual behavior of the imaginary potential observed previously in elastic
      scattering of weakly bound systems is discussed.

PMID- 12785890
TI  - Absolute collision cross sections for low energy electron scattering from NO: the
      role of resonances in elastic scattering and vibrational excitation.
AB  - Absolute measurements of elastic scattering and vibrational excitation of the NO
      molecule by low energy electron impact (0.4-2.5 eV) are presented. They show that
      previous estimates of these cross sections may be in error by as much as a factor
      of 3 and provide compelling evidence for a reassessment of the balance between
      elastic scattering and vibrational excitation at incident energies below 2 eV.
      They also confirm the critical contribution that intermediate negative ion
      resonances (NO-) make to the various scattering processes for this molecule at
      low incident energies.

PMID- 12785891
TI  - Experimental evidence for interatomic coulombic decay in Ne clusters.
AB  - Electron spectra of photoexcited Ne clusters are shown to display a signal at low
      kinetic energies that is neither present in the Ne monomer nor at photon energies
      below the inner-valence 2s threshold. These findings are strong evidence for the
      existence of interatomic Coulombic decays (ICD), a mechanism that was recently
      predicted theoretically [Phys. Rev. Lett. 79, 4778 (1997)]]. In ICD, an inner
      valence hole state in a weakly bonded system can undergo ultrafast relaxation due
      to energy transfer to a neighboring atom, followed by electron emission from this
      neighboring site.

PMID- 12785892
TI  - Resolution of the orthopositronium-lifetime puzzle.
AB  - The long-standing discrepancy [G. S. Adkins, R. N. Fell, and J. Sapirstein, Ann.
      Phys. (N.Y.) 295, 136 (2002)]] between the theoretical calculations of the
      orthopositronium (o-Ps) annihilation decay rate (lambda(T)=1/lifetime) and some
      of the experimental measurements has been resolved. A focused beam of positrons
      incident on a special nanoporous silica film produces near-thermal energy o-Ps in
      vacuum that is slow enough to be virtually free of perturbing interactions. The
      fitted decay rate requires only a 500 ppm correction for nonthermal o-Ps effects.
      The new value of lambda(T)=7.0404(10)(8) micros(-1) is in excellent agreement
      with theory.

PMID- 12785893
TI  - Controlling vibrational wave packet motion with intense modulated laser fields.
AB  - Intense, nonresonant laser fields produce Stark shifts that strongly modify the
      potential energy surfaces of a molecule. A vibrational wave packet can be guided
      by this Stark shift if the laser field is appropriately modulated during the wave
      packet motion. We modulated a 70 fs laser pulse with a period on the time scale
      of the vibrational motion (approximately 10 fs) by mixing the signal and idler of
      an optical parametric amplifier. We used ionization of H2 or D2 to launch a
      vibrational wave packet on the ground state of H2(+) or D2(+). If the laser
      intensity was high as the wave packet reached its outer turning point, the Stark
      shift allowed the molecule to dissociate through bond softening. On the other
      hand, if the field was small at this critical time, little dissociation was
      measured. By changing the modulation period, we achieved control of the
      dissociation yield with a contrast of 90%.

PMID- 12785894
TI  - Geometric phase associated with mode transformations of optical beams bearing
      orbital angular momentum.
AB  - We present direct measurements of a new geometric phase acquired by optical beams
      carrying orbital angular momentum. This phase arises when the transverse mode of
      a beam is transformed following a closed path in the space of modes. The
      measurements were done via the interference of two copropagating optical beams
      that pass through the same interferometer parts but acquire different geometric
      phases. The method is insensitive to dynamical phases. The magnitude and sign of
      the measured phases are in excellent agreement with theoretical predictions.

PMID- 12785895
TI  - Self-similar optical wave collapse: observation of the Townes profile.
AB  - Analyses of many different types of nonlinear wave equations indicate that a
      collapsing wave will transform into a universal blowup profile regardless of its
      initial shape; that is, the amplitude of the wave increases as the spatial extent
      decreases in a self-similar fashion. We show experimentally that the spatial
      profile of a collapsing optical wave evolves to a specific circularly symmetric
      shape, known as the Townes profile, for elliptically shaped or randomly distorted
      input beams. These results represent the first experimental confirmation of this
      universal collapsing behavior and provide deeper insight into the high-power
      filamentation of femtosecond laser pulses in air.

PMID- 12785896
TI  - Breakdown of diffusion in dynamics of extended waves in mesoscopic media.
AB  - We report the observation of nonexponential decay of pulsed microwave
      transmission through quasi-one-dimensional random dielectric media signaling the
      breakdown of the diffusion model. The decay rate of transmission falls nearly
      linearly in time corresponding to a nearly Gaussian distribution of the coupling
      strengths of quasinormal electromagnetic modes to free space at the sample
      surfaces. The peak and width of this distribution scale as L(-2.05) and L(-1.81),
      respectively.

PMID- 12785897
TI  - Color of shock waves in photonic crystals.
AB  - Unexpected and stunning new physical phenomena result when light interacts with a
      shock wave or shocklike dielectric modulation propagating through a photonic
      crystal. These new phenomena include the capture of light at the shock wave front
      and reemission at a tunable pulse rate and carrier frequency across the band gap,
      and bandwidth narrowing as opposed to the ubiquitous bandwidth broadening. To our
      knowledge, these effects do not occur in any other physical system and are all
      realizable under experimentally accessible conditions. Furthermore, their
      generality make them amenable to observation in a variety of time-dependent
      photonic crystal systems, which has significant technological implications.

PMID- 12785898
TI  - Stochastic theory of synchronization transitions in extended systems.
AB  - We propose a general Langevin equation describing the universal properties of
      synchronization transitions in extended systems. By means of theoretical
      arguments and numerical simulations we show that the proposed equation exhibits,
      depending on parameter values: (i) a continuous transition in the bounded Kardar
      Parisi-Zhang universality class, with a zero largest Lyapunov exponent at the
      critical point; (ii) a continuous transition in the directed percolation class,
      with a negative Lyapunov exponent, or (iii) a discontinuous transition (that is
      argued to be possibly just a transient effect). Cases (ii) and (iii) exhibit
      coexistence of synchronized and unsynchronized phases in a broad (fuzzy) region.
      This reproduces almost all of the reported features of synchronization
      transitions, providing a unified theoretical framework for the analysis of
      synchronization transitions in extended systems.

PMID- 12785899
TI  - Anticipating the response of excitable systems driven by random forcing.
AB  - We study the regime of anticipated synchronization in unidirectionally coupled
      model neurons subject to a common external aperiodic forcing that makes their
      behavior unpredictable. We show numerically and by analog hardware electronic
      circuits that, under appropriate coupling conditions, the pulses fired by the
      slave neuron anticipate (i.e., predict) the pulses fired by the master neuron.
      This anticipated synchronization occurs even when the common external forcing is
      white noise.

PMID- 12785900
TI  - Static criteria for the existence of Coulomb strings in storage rings.
AB  - We derive four rigorous conditions for the stability of Coulomb strings in
      circular storage rings. These criteria are well met by the existing data from
      experiments in SIS, ESR, and CRYring but not by the NAP-M experiment. We
      calculate the potential of the joint transverse zigzag excitation and the
      longitudinal motion against each other of a string of charged particles as a
      function of their amplitudes and with the linear density as parameter. This
      potential exhibits a saddle point in amplitude space which, if overcome, destroys
      the order of the string. The conditions of stability are derived from the
      position and height of the saddle point which are fairly independent of the
      linear density. Our findings confirm the supposition that only the Coulomb
      interaction in the immediate vicinity of very close encounters of particles is
      important for the existence of strings.

PMID- 12785902
TI  - Ultrarelativistic-positron-beam transport through meter-scale plasmas.
AB  - We report on the first study of the dynamic transverse forces imparted to an
      ultrarelativistic positron beam by a long plasma in the underdense regime.
      Focusing of the 28.5 GeV beam is observed from time-resolved beam profiles after
      the 1.4 m plasma. The strength of the imparted force varies along the
      approximately 12 ps full length of the bunch as well as with plasma density.
      Computer simulations substantiate the longitudinal aberration seen in the data
      and reveal mechanisms for emittance degradation.

PMID- 12785903
TI  - Density peaking, anomalous pinch, and collisionality in tokamak plasmas.
AB  - The existence of an anomalous particle pinch in magnetized tokamak plasmas is
      still questioned. Contradictory observations have been collected so far in
      tokamaks. Clear experimental evidence that density peaking in tokamak plasmas
      drops with increasing collisionality is provided for the first time. This
      phenomenon is explained by means of existing theoretical models based on the
      fluid description of drift wave instabilities, provided that such models include
      the dissipative effects introduced by collisions on the mentioned instabilities.
      These results reconcile the apparent contradictions found so far in the
      experiments.

PMID- 12785901
TI  - Sawtooth oscillation in current-carrying plasma in the large helical device.
AB  - Sawtooth oscillations have been observed in current-carrying helical plasmas by
      using electron-cyclotron-emission diagnostics in the Large Helical Device. The
      plasma current, which is driven by neutral beam injection, reduces the beta
      threshold of the sawtooth oscillation. When the central q value is increased due
      to the plasma current, the core region crashes, and, when it is decreased, the
      edge region crashes annularly. Observed rapid mixture of the plasma in the
      limited region suggests that these sawtooth crashes are reconnection phenomena.
      Unlike previous experiments, no precursor oscillation has been observed.

PMID- 12785904
TI  - Rotating superfluid turbulence.
AB  - Almost all studies of vortex states in helium II have been concerned with either
      ordered vortex arrays or disordered vortex tangles. This work numerically studies
      what happens in the presence of both rotation (which induces order) and thermal
      counterflow (which induces disorder). We find a new statistically steady state in
      which the vortex tangle is polarized along the rotational axis. Our results are
      used to interpret an instability that was discovered experimentally by Swanson et
      al. [Phys. Rev. Lett. 50, 190 (1983)]] and the vortex state beyond the
      instability that has been unexplained until now.

PMID- 12785905
TI  - Dielectric constant of glasses: evidence for dipole-dipole interactions.
AB  - The 1 kHz real part chi(') of the dielectric constant of a structural glass (a
      SiO(2+x)C(1+y)H(z)) was measured at low temperature T. Reducing the sample
      thickness h below 100 nm weakens the slope /delta(chi('))/delta (T) for T less
      than or approximately equal 0.1 K, for all measuring fields E. This contrasts
      with the predictions of the two-level system (TLS) model but is in agreement with
      the recently proposed delocalization of excitations derived from a field-induced
      TLS-TLS interaction mechanism. For small h this interaction is screened, which
      explains the h effects on chi('). Hence, interactions must play a key role in
      standard thick samples as soon as T less than or approximately equal 0.1 K.

PMID- 12785906
TI  - Specific-heat anomaly caused by ferroelectric nanoregions in Pb(Mg(1/3)Nb(2/3))O3
      and Pb(Mg(1/3)Ta(2/3))O3 relaxors.
AB  - The specific heat of typical relaxors, Pb(Mg(1/3)Nb(2/3))O3 (PMN) and
      Pb(Mg(1/3)Ta(2/3))O3 (PMT), was measured by adiabatic and relaxation methods
      between 2 and 420 K. A broad anomaly was found in the specific heat curve over
      the wide temperature range between 150 and 500 K for PMN, and between 50 and 400
      K for PMT, which provides evidence for the formation of ferroelectric nanoregions
      (FNR) in the paraelectric matrix. The entropy of the anomaly was estimated as 3.3
      J K(-1) mol(-1) and 2.9 J K(-1) mol(-1) for PMN and PMT, respectively, which
      implies an order-disorder-type mechanism for the formation of FNR.

PMID- 12785907
TI  - Hyperthermal molecular beam deposition of highly ordered organic thin films.
AB  - We use a seeded supersonic molecular beam to control the kinetic energy of
      pentacene (C22H14) during deposition and growth on Ag(111). Highly ordered thin
      films are grown at low substrate temperatures (approximately 200 K) at kinetic
      energies of a few electron volts, as shown by low energy He diffraction and x-ray
      reflectivity spectra. In contrast, deposition of thermal molecules yields only
      amorphous films. Growth at room or higher temperature substrates yields films of
      poorer quality irrespective of the depositing beam energy. We find that after the
      first wetting layer is completed, a new ordered phase is formed, whose in-plane
      lattice spacings match one of the bulk crystal planes. The high quality of the
      films can be interpreted as the result of local annealing induced by the impact
      of the impinging high-energy molecules.

PMID- 12785908
TI  - Active role of oxide support during CO oxidation at Au/MgO.
AB  - The oxidation of CO at MgO supported gold aggregates is studied by means of
      density functional theory calculations. In addition to serving as a structural
      promoter holding the gold particles, the supporting oxide also takes an active
      role in the bonding and activation of adsorbates bound to the gold. The oxide
      stabilizes a peroxolike reaction intermediate, CO.O2, and causes steric repulsion
      to CO. The most reactive site at Au/MgO appears where the gold shelters the MgO
      thereby creating a cavity where several low-coordinated Au atoms and Mg2+ cations
      from the substrate can interact simultaneously with an adsorbate.

PMID- 12785909
TI  - Electron-polariton scattering in semiconductor microcavities.
AB  - In semiconductor microcavities, electron-polariton scattering has been proposed
      as an efficient process that can drive polaritons from the bottleneck region to
      the ground state, achieving Bose amplification of the optical emission. We
      present clear experimental observation of this process in a structure that allows
      control of the electron density and we report substantial enhancement of
      photoluminescence. We show that this enhancement is more effective at higher
      temperatures due to the different way that electron scattering processes either
      broaden or relax polaritons.

PMID- 12785910
TI  - Quantized anomalous Hall effect in two-dimensional ferromagnets: quantum Hall
      effect in metals.
AB  - We study the effect of disorder on the anomalous Hall effect (AHE) in two
      dimensional ferromagnets. The topological nature of the AHE leads to the integer
      quantum Hall effect from a metal, i.e., the quantization of sigma(xy) induced by
      the localization except for the few extended states carrying Chern numbers.
      Extensive numerical study on a model reveals that Pruisken's two-parameter
      scaling theory holds even when the system has no gap with the overlapping
      multibands and without the uniform magnetic field. Therefore, the condition for
      the quantized AHE is given only by the Hall conductivity sigma(xy) without the
      quantum correction, i.e., /sigma(xy)/>e(2)/(2h).

PMID- 12785911
TI  - Tailorable acceptor C(60-n)B(n) and donor C(60-m)N(m) pairs for molecular
      electronics.
AB  - Our first-principles calculations demonstrate that C(60-n)B(n) and C(60-m)N(m)
      can be engineered as the acceptors and donors, respectively, needed for molecular
      electronics by properly controlling the dopant number n and m in C60. We show
      that acceptor C48B12 and donor C48N12 are promising components for molecular
      rectifiers, carbon nanotube-based n-p-n (p-n-p) transistors, and p-n junctions.

PMID- 12785912
TI  - Stochastic path integral formulation of full counting statistics.
AB  - We derive a stochastic path integral representation of counting statistics in
      semiclassical systems. The formalism is introduced on the simple case of a single
      chaotic cavity with two quantum point contacts, and then further generalized to
      find the propagator for charge distributions with an arbitrary number of counting
      fields and generalized charges. The counting statistics is given by the saddle
      point approximation to the path integral, and fluctuations around the saddle
      point are suppressed in the semiclassical approximation. We use this approach to
      derive the current cumulants of a chaotic cavity in the hot-electron regime.

PMID- 12785913
TI  - High-finesse optical quantum gates for electron spins in artificial molecules.
AB  - A doped semiconductor double-quantum-dot molecule is proposed as a qubit
      realization. The quantum information is encoded in the electron spin, thus
      benefiting from the long relevant decoherence times; the enhanced flexibility of
      the molecular structure allows one to map the spin degrees of freedom onto the
      orbital ones and vice versa and opens the possibility for high-finesse
      (conditional and unconditional) quantum gates by means of stimulated Raman
      adiabatic passages.

PMID- 12785914
TI  - Long-lived memory for mesoscopic quantum bits.
AB  - We describe a technique to create long-lived quantum memory for quantum bits in
      mesoscopic systems. Specifically we show that electronic spin coherence can be
      reversibly mapped onto the collective state of the surrounding nuclei. The
      coherent transfer can be efficient and fast and it can be used, when combined
      with standard resonance techniques, to reversibly store coherent superpositions
      on the time scale of seconds. This method can also allow for "engineering"
      entangled states of nuclear ensembles and efficiently manipulating the stored
      states. We investigate the feasibility of this method through a detailed analysis
      of the coherence properties of the system.

PMID- 12785915
TI  - Anomalous enhancement of the coupling to the magnetic resonance mode in
      underdoped Pb-Bi2212.
AB  - High-resolution angle-resolved photoemission with variable excitation energies is
      used to disentangle bilayer splitting effects and intrinsic (self-energy) effects
      in the electronic spectral function near the (pi,0) point of differently doped
      (Pb,Bi)(2)Sr(2)CaCu(2)O(8+delta). In contrast to overdoped samples, where
      intrinsic effects at the (pi,0) point are virtually absent, we find in underdoped
      samples intrinsic effects in the superconducting-state (pi,0) spectra of the
      antibonding band. This intrinsic effect is present only below the critical
      temperature and weakens considerably with doping. Our results give strong support
      for models which involve a strong coupling of electronic excitations with the
      resonance mode seen in inelastic neutron scattering experiments.

PMID- 12785916
TI  - Gossamer superconductor, Mott insulator, and resonating valence bond state in
      correlated electron systems.
AB  - Gutzwiller variational method is applied to an effective two-dimensional Hubbard
      model to examine the recently proposed gossamer superconductor by Laughlin (LANL
      cond-mat/0209269). The ground state at half filled electron density is a gossamer
      superconductor for smaller intrasite Coulomb repulsion U and a Mott insulator for
      larger U. The gossamer superconducting state is similar to the resonating valence
      bond superconducting state, except that the chemical potential is approximately
      pinned at the mid of the two Hubbard bands away from the half filled.

PMID- 12785917
TI  - Crossover from coherent to incoherent electronic excitations in the normal state
      of Bi(2)Sr(2)CaCu(2)O(8+delta).
AB  - Angle resolved photoemission spectroscopy (ARPES) and resistivity measurements
      are used to explore the overdoped region of the high temperature superconductor
      Bi(2)Sr(2)CaCu(2)O(8+delta). We find evidence for a new crossover line in the
      phase diagram between a coherent metal phase, for lower temperatures and higher
      doping, and an incoherent metal phase, for higher temperatures and lower doping.
      The former is characterized by two well-defined spectral peaks in ARPES due to
      coherent bilayer splitting and superlinear behavior in the resistivity, whereas
      the latter is characterized by a single broad spectral feature in ARPES and a
      linear temperature dependence of the resistivity.

PMID- 12785918
TI  - Quantum Andreev map: a paradigm of quantum chaos in superconductivity.
AB  - We introduce quantum maps with particle-hole conversion (Andreev reflection) and
      particle-hole symmetry, which exhibit the same excitation gap as quantum dots in
      the proximity to a superconductor. Computationally, the Andreev maps are much
      more efficient than billiard models of quantum dots. This makes it possible to
      test analytical predictions of random-matrix theory and semiclassical chaos that
      were previously out of reach of computer simulations. We have observed the
      universal distribution of the excitation gap for a large Lyapunov exponent and
      the logarithmic reduction of the gap when the Ehrenfest time becomes comparable
      to the quasiparticle dwell time.

PMID- 12785919
TI  - Andreev reflections on Y(1-x)Ca(x)Ba(2)Cu(3)O(7-delta): evidence for an unusual
      proximity effect.
AB  - We have measured Andreev reflections between an Au tip and Y(1
      x)Ca(x)Ba(2)Cu(3)O(7-delta) thin films in the in-plane orientation. The
      conductance spectra are best fitted with a pair potential having the d(x2-y2)+is
      symmetry. We find that the amplitude of the is component is enhanced as the
      contact transparency is increased. This is an indication for an unusual proximity
      effect that modifies the pair potential in the superconductor near the surface
      with the normal metal.

PMID- 12785920
TI  - c-Axis Raman scattering spectra of MgB2: observation of a dirty-limit gap in the
      pi bands.
AB  - Raman scattering spectra from the ac face of thick MgB2 single crystals were
      measured in zz, xz, and xx polarizations. In zz and xz polarizations a threshold
      at around 29 cm(-1) forms in the below T(c) continuum but no pair-breaking peak
      is seen, in contrast to the sharp pair-breaking peak at around 100 cm(-1) in xx
      polarization. The zz and xz spectra are consistent with Raman scattering from a
      dirty superconductor while the sharp peak in the xx spectra argues for a clean
      system. Analysis of the spectra resolves this contradiction, placing the larger
      and smaller gap magnitudes in the sigma and pi bands and indicating that
      relatively strong impurity scattering is restricted to the pi bands.

PMID- 12785921
TI  - Electronic structure and the Fermi surface of PuCoGa5 and NpCoGa5.
AB  - Using a relativistic linear augmented-plane-wave method, we clarify energy band
      structures and Fermi surfaces of recently discovered plutonium-based
      superconductor PuCoGa5 and the isostructural material NpCoGa5. For PuCoGa5, we
      find several cylindrical sheets of Fermi surfaces with large volume, similar to
      CeMIn5, while for NpCoGa5, the Fermi surfaces are found to be similar to those of
      UMGa5. These similarities are discussed based on the j-j coupling scheme,
      suggesting some hints for the superconducting mechanism in HoCoGa5-type f
      electron compounds.

PMID- 12785922
TI  - Coarse graining in micromagnetics.
AB  - Numerical solutions of the micromagnetic Landau-Lifshitz-Gilbert equations
      provide valuable information at low temperatures (T), but produce egregious
      errors at higher T. For example, Curie temperatures are often overestimated by an
      order of magnitude. We show that these errors result from the use of block or
      coarse-grained variables, without a concomitant renormalization of the system
      parameters to account for the block size. Renormalization solves the problem of
      the Curie-point anomaly and improves the accuracy of more complicated
      micromagnetic simulations, even at low T.

PMID- 12785923
TI  - Room-temperature ferromagnetism in a II-VI diluted magnetic semiconductor Zn(1
      x)Cr(x)Te.
AB  - The magnetic and magneto-optical properties of a Cr-doped II-VI semiconductor
      ZnTe were investigated. Magnetic circular dichroism measurements showed a strong
      interaction between the sp carriers and localized d spins, indicating that Zn(1
      x)Cr(x)Te is a diluted magnetic semiconductor. The Curie temperature of the film
      with x=0.20 was estimated to be 300+/-10 K, which is the highest value ever
      reported for a diluted magnetic semiconductor in which sp-d interactions were
      confirmed. In spite of its high Curie temperature, Zn(1-x)Cr(x)Te film shows
      semiconducting electrical transport properties.

PMID- 12785924
TI  - Electronic control of spin alignment in pi-conjugated molecular magnets.
AB  - Intramolecular spin alignment in pi-conjugated molecules is studied theoretically
      in a model of a Peierls-Hubbard chain coupled with two localized spins. By means
      of the exact diagonalization technique, we demonstrate that a spin singlet (S=0)
      to quartet (S=3/2) transition can be induced by electronic doping, depending on
      the chain length, the positions of the localized spins, and the sign of the
      electron-spin coupling. The calculated results provide a theoretical basis for
      understanding the mechanism of spin alignment recently observed in a diradical
      donor molecule.

PMID- 12785925
TI  - Effects of the Dzyaloshinskii-Moriya interaction on low-energy magnetic
      excitations in copper benzoate.
AB  - We have investigated the physical effects of the Dzyaloshinskii-Moriya (DM)
      interaction in copper benzoate. In the low-field limit, the spin gap is found to
      vary as H(2/3)ln((1/6)(J/mu(B)H(s)) (H(s): an effective staggered field induced
      by the external field H) in agreement with the prediction of conformal field
      theory, while the staggered magnetization varies as H(1/3) and the
      ln((1/3)(J/mu(B)H(s)) correction predicted by conformal field theory is not
      confirmed. The linear scaling relation between the momentum shift and the
      magnetization is broken. We have determined the coupling constant of the DM
      interaction and have given a complete quantitative account for the field
      dependence of the spin gaps along all three principal axes, without resorting to
      additional interactions such as interchain coupling. A crossover to strong
      applied field behavior is predicted for further experimental verification.

PMID- 12785926
TI  - Observation of a liquid-gas-type transition in the pyrochlore spin ice compound
      Dy2Ti2O7 in a magnetic field.
AB  - Low temperature magnetization measurements on the pyrochlore spin ice compound
      Dy2Ti2O7 reveal that the ice-rule breaking spin flip, appearing at H
      approximately 0.9 T applied parallel to the [111] direction, turns into a novel
      first-order transition for T<0.36 K which is most probably of a liquid-gas type.
      T-linear variation of the critical field observed down to 0.03 K suggests the
      unusual situation that the entropy release across the transition remains finite
      [approximately 0.5 (J/K) x mol-Dy] as T-->0, in accordance with a breaking of the
      macroscopic degeneracy in the intermediate "kagome ice" state.

PMID- 12785927
TI  - Ratio problem in single carbon nanotube fluorescence spectroscopy.
AB  - The electronic band gaps measured in fluorescence spectroscopy on individual
      single wall carbon nanotubes isolated within micelles show significant deviations
      from the predictions of one electron band theory. We resolve this problem by
      developing a theory of the electron-hole interaction in the photoexcited states.
      The one-dimensional character and tubular structure introduce a novel relaxation
      pathway for carriers photoexcited above the fundamental band edge. Analytic
      expression for the energies and line shapes of higher subband excitons are
      derived, and a comparison with experiment is used to extract the value of the
      screened electron-hole interaction.

PMID- 12785928
TI  - Experimental realization of entanglement concentration and a quantum repeater.
AB  - We report an experimental realization of entanglement concentration using two
      polarization-entangled photon pairs produced by pulsed parametric down
      conversion. In the meantime, our setup also provides a proof-in-principle
      demonstration of a quantum repeater. The quality of our procedure is verified by
      observing a violation of Bell's inequality by more than 5 standard deviations.
      The high experimental accuracy achieved in the experiment implies that the
      requirement of tolerable error rate in multistage realization of quantum
      repeaters can be fulfilled, hence providing a useful toolbox for quantum
      communication over large distances.

PMID- 12785929
TI  - Liquid-liquid phase separation of a surfactant-solubilized membrane protein.
AB  - Solubilization of membrane proteins requires surfactants, whose structural
      properties play a crucial role in determining the protein phase behavior. We show
      that ionization of a pH-sensitive surfactant, lauryldymethylamino-N-oxide, bound
      to the bacterial photosynthetic Reaction Center, induces protein phase
      segregation in micrometric "droplets." Liquid-liquid phase separation takes place
      in a narrow pH range, is promoted by increasing temperature, and vanishes by
      adding salt. After a fast initial droplet growth, the nearly arrested kinetics at
      a later stage leaves the system in a finely divided, long-lasting emulsified
      state.

PMID- 12785931
TI  - Comment on "No-signaling condition and quantum dynamics".

PMID- 12785930
TI  - Dissociative electron attachment to DNA.
AB  - Electron-stimulated desorption of anions from thin films of linear and
      supercoiled DNA is investigated in the range 3-20 eV. Resonant structures are
      observed with maxima at 9.4+/-0.3, 9.2+/-0.3, and 9.2+/-0.3 eV, respectively, in
      the yield dependence of H-, O-, and OH- on the incident electron energy. Their
      formation is attributed to dissociative electron attachment.

PMID- 12785933
TI  - Kochen-Specker theorem for a single qubit using positive operator-valued
      measures.
AB  - A proof of the Kochen-Specker theorem for a single two-level system is presented.
      It employs five eight-element positive operator-valued measures and a simple
      algebraic reasoning based on the geometry of the dodecahedron.

PMID- 12785934
TI  - Berry phase in a nonisolated system.
AB  - We investigate the effect of the environment on a Berry phase measurement
      involving a spin-half. We model the spin + environment using a biased spin-boson
      Hamiltonian with a time-dependent magnetic field. We find that, contrary to naive
      expectations, the Berry phase acquired by the spin can be observed, but only on
      time scales which are neither too short nor very long. However this Berry phase
      is not the same as for the isolated spin-half. It does not have a simple
      geometric interpretation in terms of the adiabatic evolution of either bare spin
      states or the dressed spin resonances. This result is crucial for proposed Berry
      phase measurements in superconducting nanocircuits.

PMID- 12785935
TI  - Phase transition in the 2D random Potts model in the large-q limit.
AB  - Phase transition in the two-dimensional q-state Potts model with random
      ferromagnetic couplings is studied in the large-q limit by a combinatorial
      optimization algorithm and by approximate mappings. We conjecture that the
      critical behavior of the model is controlled by the isotropic version of the
      infinite randomness fixed point of the random transverse-field Ising spin chain
      and the critical exponents are exactly given by beta=(3-sqrt[5])/4, beta(s)=1/2,
      and nu=1. The specific heat has a logarithmic singularity, but at the transition
      point there are very strong sample-to-sample fluctuations. Discretized randomness
      results in discontinuities in the internal energy.

PMID- 12785936
TI  - MHD shocks and the origin of the solar transition region.
AB  - Simultaneous observations of the solar atmosphere from its surface to the corona
      obtained with the Solar and Heliospheric Observatory (SOHO) and Transition Region
      and Coronal Explorer (TRACE) show a ubiquitous sequence of events that start from
      cancellation of photospheric magnetic fields, pass through shock formation, and
      result in transition region supersonic jets and microflares. These results
      support a novel view of the energy buildup in the solar atmosphere associated
      with a cascade of shock waves produced by interacting network magnetic elements
      in the photosphere and provide insight into the origin of the solar transition
      region. The findings account for the general mechanisms of energy production,
      transfer, and release throughout the Sun's and stellar atmospheres.

PMID- 12785937
TI  - Neutrinos from pulsar wind bubbles as precursors to gamma-ray bursts.
AB  - The supranova model for gamma-ray bursts (GRBs) has recently gained popularity.
      In this scenario the GRB occurs weeks to years after a supernova explosion, and
      is located inside a pulsar wind bubble (PWB). High energy protons from the PWB
      can interact with photons from the rich radiation field inside the PWB or collide
      with cold protons from the supernova remnant, producing pions which decay into
      approximately 10-10(3) TeV neutrinos. The predicted neutrino flux from the PWBs
      that host the GRBs should be easily detectable by planned 1 km(2) detectors.

PMID- 12785938
TI  - Ultrahigh energy cosmic rays, cosmological constant, and theta vacua.
AB  - We propose that the origin of ultrahigh energy cosmic rays beyond the Greisen
      Zatsepin-Kuzmin cutoff and the origin of small cosmological constant can both be
      explained by vacuum tunneling effects in a theory with degenerate vacua and
      fermionic doublets. By considering the possibility of tunneling from a particular
      winding number state, accompanied by violation of some global quantum number of
      fermions, the small value of the vacuum dark energy and the production of high
      energy cosmic rays are shown to be related. We predict that the energy of such
      cosmic rays should be at least 5x10(14) GeV.

PMID- 12785940
TI  - Precision neutron interferometric measurement of the nd coherent neutron
      scattering length and consequences for models of three-nucleon forces.
AB  - We have performed the first high precision measurement of the coherent neutron
      scattering length of deuterium in a pure sample using neutron interferometry. We
      find b(nd)=(6.665+/-0.004) fm in agreement with the world average of previous
      measurements using different techniques, b(nd)=(6.6730+/-0.0045) fm. We compare
      the new world average for the nd coherent scattering length b(nd)=(6.669+/-0.003)
      fm to calculations of the doublet and quartet scattering lengths from several
      modern nucleon-nucleon potential models with three-nucleon force (3NF) additions
      and show that almost all theories are in serious disagreement with experiment.
      This comparison is a more stringent test of the models than past comparisons with
      the less precisely determined doublet scattering length of (2)a(nd)=(0.65+/-0.04)
      fm.

PMID- 12785939
TI  - Compton scattering from the deuteron and extracted neutron polarizabilities.
AB  - Differential cross sections for Compton scattering from the deuteron were
      measured at MAX-Lab for incident photon energies of 55 and 66 MeV at nominal
      laboratory angles of 45 degrees, 125 degrees, and 135 degrees. Tagged photons
      were scattered from liquid deuterium and detected in three NaI spectrometers. By
      comparing the data with theoretical calculations in the framework of a one-boson
      exchange potential model, the sum and the difference of the isospin-averaged
      nucleon polarizabilities, alpha(N)+beta(N)=17.4+/-3.7 and alpha(N)-beta(N)=6.4+/
      2.4 (in units of 10(-4) fm(3)), have been determined. By combining the latter
      with the global-averaged value for alpha(p)-beta(p) and using the predictions of
      the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained
      values for the neutron electric and magnetic polarizabilities of alpha(n)=8.8+/
      2.4(total)+/-3.0(model) and beta(n)=6.5-/+2.4(total)-/+3.0(model), respectively.

PMID- 12785941
TI  - Double incoherent Raman scattering induced by molecular interactions in gases.
AB  - A new Raman band is observed in two gases, CF4 and CH4. It is attributable to a
      double incoherent Raman scattering that takes place in pairs of interacting
      molecules. Spectral scattering intensities are given on an absolute scale. Zero
      order spectral moments are measured and are found higher than their long-range
      interaction value.

PMID- 12785942
TI  - Single-stage sub-Doppler cooling of alkaline earth atoms.
AB  - We report the first experimental study of sub-Doppler cooling in alkaline earth
      atoms (87Sr) enabled by the presence of nuclear spin-originated magnetic
      degeneracy in the atomic ground state. Sub-Doppler cooling in a sigma(+)-sigma(-)
      configuration is achieved despite the presence of multiple, closely spaced
      excited states. This surprising result is confirmed by an expanded multilevel
      theory of the radiative cooling force. Detailed investigations of system
      performance have shed new insights into (sigma(+)-sigma(-)) cooling dynamics and
      will likely play an important role in the future development of neutral atom
      based optical frequency standards.

PMID- 12785943
TI  - Resonant neutral-particle emission in collisions of electrons with peptide ions
      in a storage ring.
AB  - Electron-biomolecular ion collisions were studied using an electrostatic storage
      ring with a merging beam technique for singly protonated peptides (angiotensin I,
      II, and III). A strong neutral-particle emission at around 6.5 eV was found in
      addition to neutrals from recombination at low energies. The rates of the high
      energy peak greatly decreased with a slight decrease in the number of amino-acid
      residues from angiotensin I to III. These results suggest that some peptide bonds
      were selectively cleaved.

PMID- 12785944
TI  - Direct measurement of the parapositronium lifetime in alpha-SiO2.
AB  - The mean lifetime of delocalized parapositronium in alpha-SiO2 has been
      determined directly for the first time using a newly developed positron lifetime
      spectrometer based on BaF2 scintillators and a fast digital oscilloscope. The
      lifetime is found to be 156+/-4 ps, which is much longer than its intrinsic
      lifetime of 125 ps. This indicates clearly that the primary many-body effect on
      positronium in alpha-SiO2 is the screening of the Coulomb interaction between the
      constituent particles by electrons of the medium and that the average distance
      between the electron and positron in positronium becomes larger than its vacuum
      value.

PMID- 12785945
TI  - Ancilla-assisted quantum process tomography.
AB  - Complete and precise characterization of a quantum dynamical process can be
      achieved via the method of quantum process tomography. Using a source of
      correlated photons, we have implemented several methods, each investigating a
      wide range of processes, e.g., unitary, decohering, and polarizing. One of these
      methods, ancilla-assisted process tomography (AAPT), makes use of an additional
      "ancilla system," and we have theoretically determined the conditions when AAPT
      is possible. Surprisingly, entanglement is not required. We present data obtained
      using both separable and entangled input states. The use of entanglement yields
      superior results, however.

PMID- 12785946
TI  - Global optimization of high harmonic generation.
AB  - We investigate the relevance of the absorption limit concept in the optimization
      of high harmonic generation. Thanks to the first direct observation of the
      coherence length of the process from high-contrast Maker fringes, we unravel
      experimental conditions for which the harmonic dipole response is enhanced when
      phase matching is realized within the absorption limit, leading to record
      conversion efficiencies in argon. Moreover, we show that harmonic generation in
      guided or freely propagating geometries are equivalent in the loose focusing
      regime. This analysis is generalized to other advanced phase-matching schemes,
      thereby predicting the possibility to boost the conversion efficiencies using
      light noble gases.

PMID- 12785947
TI  - Early dynamics of guest-host interaction in dye-doped liquid crystalline
      materials.
AB  - We have studied in detail the early dynamics of laser-induced molecular
      reorientation in a dye-doped liquid crystalline (LC) medium that exhibits a
      significant enhancement of the optical Kerr nonlinearity due to guest-host
      interaction. Experimental results agree quantitatively with theory based on a
      model in which the anisotropic dye excitation helps reorient the LC molecules
      through a mean-field intermolecular interaction.

PMID- 12785948
TI  - Experimental verification of anticipated and retarded synchronization in chaotic
      semiconductor lasers.
AB  - Experimental observation of both anticipated and retarded synchronization is
      demonstrated using unidirectionally coupled semiconductor lasers with delayed
      optoelectronic feedback. Depending on the difference between the transmission
      time and the feedback delay time, the lasers fall into either the anticipated or
      the retarded synchronization regime, where the driven receiver laser leads or
      lags behind the driving transmitter laser. The two regimes are observed to have
      the same stability of chaos synchronization in the presence of small
      perturbations by noise and parameter mismatches. In both regimes the observed
      time shift between the synchronized chaotic waveforms is found to be equal to the
      difference between the transmission time and the feedback delay time.

PMID- 12785949
TI  - Ray-splitting correction to the Weyl formula: experiment versus theory.
AB  - An abrupt change in the dielectric constant of media filling a microwave cavity
      was predicted by Prange et al. [Phys. Rev. E 53, 207 (1996)]] to produce a ray
      splitting correction to the Weyl formula for the mean staircase function of
      resonances. We present the first experimental confirmation of this effect. Our
      results with a quasi-two-dimensional cavity are directly relevant to the ray
      splitting correction in two-dimensional quantal ray-splitting billiards.

PMID- 12785950
TI  - Low-speed impact craters in loose granular media.
AB  - We report on craters formed by balls dropped into dry, noncohesive, granular
      media. By explicit variation of ball density rho(b), diameter D(b), and drop
      height H, the crater diameter is confirmed to scale as the 1/4 power of the
      energy of the ball at impact: D(c) approximately equal (rho(b)D(3)(b)H)(1/4).
      Against expectation, a different scaling law is discovered for the crater depth:
      d approximately equal (rho(3/2)(b)D(2)(b)H)(1/3). The scaling with properties of
      the medium is also established. The crater depth has significance for granular
      mechanics in that it relates to the stopping force on the ball.

PMID- 12785951
TI  - Sheared poloidal flow driven by mode conversion in tokamak plasmas.
AB  - A two-dimensional integral full-wave model is used to calculate poloidal forces
      driven by mode conversion in tokamak plasmas. In the presence of a poloidal
      magnetic field, mode conversion near the ion-ion hybrid resonance is dominated by
      a transition from the fast magnetosonic wave to the slow ion cyclotron wave. The
      poloidal field generates strong variations in the parallel wave spectrum that
      cause wave damping in a narrow layer near the mode conversion surface. The
      resulting poloidal forces in this layer drive sheared poloidal flows comparable
      to those in direct launch ion Bernstein wave experiments.

PMID- 12785952
TI  - Sound propagation in coexistent Bose and Fermi superfluids in aerogel.
AB  - We report the first observation of longitudinal sound propagation in three
      dimensionally distributed Bose and Fermi superfluids in an acoustic investigation
      of phase separated 3He-4He mixtures confined to aerogel. At mK temperatures, this
      inhomogeneous system exhibits simultaneous 3He and 4He superfluidity leading to
      two "slow modes" along with the conventional sound mode. We also infer the
      superfluidity of isolated bubbles of pure 3He in a large 4He concentration
      sample.

PMID- 12785953
TI  - Memory effects in amorphous solids below 20 mK.
AB  - At temperatures below 1 K, the capacitance of a glass sample changes due to the
      application of a dc field in accordance with Burin's dipole gap theory [J. Low
      Temp. Phys. 100, 309 (1995)]]. However, we now report that below 20 mK, during
      the first sweep cycle of the dc electric field, the capacitance is smaller by
      about 10(-5) compared to any subsequent sweep. Despite this overall shift, the
      field dependence follows the dipole gap predictions. In a subsequent sweep to
      higher dc fields the dielectric constant drops by about 10(-5) as soon as the
      applied field is higher than any field previously applied. A picture involving
      the dynamics of resonant pairs provides a qualitative description of this
      behavior.

PMID- 12785954
TI  - Diffusion in a metallic melt at the critical temperature of mode coupling theory.
AB  - According to mode coupling theory, liquidlike motion becomes frozen at a critical
      temperature T(c) well above the caloric glass transition temperature T(g). Here,
      for the first time, we report on radiotracer diffusion in a supercooled
      Pd43Cu27Ni10P20 alloy from T(g) to the equilibrium melt. Liquidlike motion is
      seen to set in exactly above T(c) as evidenced by a gradual drop of the effective
      activation energy. This strongly supports the mode coupling scenario. Isotope
      effect measurements, which have never been carried out near T(c) in any material,
      show atomic transport up to the equilibrium melt to be far away from the
      hydrodynamic regime of uncorrelated binary collisions.

PMID- 12785955
TI  - Water alignment and proton conduction inside carbon nanotubes.
AB  - First-principles molecular dynamics simulations have been carried out to
      investigate the structure, electronic properties, and proton conductivity of
      water confined inside single-walled carbon nanotubes. The simulations predict the
      formation of a strongly connected one-dimensional hydrogen-bonded water wire
      resulting in a net electric dipole moment directed along the nanotube axis. An
      excess proton injected into the water wire is found to be significantly
      stabilized, relative to the gas phase, due to the high polarizability of the
      carbon nanotube.

PMID- 12785956
TI  - First x-ray scattering studies on electrostatically levitated metallic liquids:
      demonstrated influence of local icosahedral order on the nucleation barrier.
AB  - To explain the unusual stability of undercooled liquids against crystallization,
      Frank hypothesized that the local structures of undercooled liquids contain a
      significant degree of icosahedral short-range order, which is incompatible with
      long-range periodicity. We present here the first direct experimental
      demonstration of Frank's complete hypothesis, showing a correlation between the
      nucleation barrier and a growing icosahedral short-range order with decreasing
      temperature in a Ti39.5Zr39.5Ni21 liquid. A new experimental facility, BESL
      (Beamline Electrostatic Levitation), was developed to enable the synchrotron x
      ray structural studies on deeply undercooled, reactive liquids.

PMID- 12785957
TI  - Continuous freezing in three dimensions.
AB  - We analyze the freezing transition in a system of hard particles with a very long
      ranged repulsion. The long-range repulsion makes first-order freezing transitions
      continuous, but leaves the initial stages of the crystallization unchanged: the
      crystal phase must still nucleate. The coexistence between bulk phases is
      replaced by microphase separation.

PMID- 12785958
TI  - Wetting in a colloidal liquid-gas system.
AB  - We present first observations of wetting phenomena in depletion interaction
      driven, phase separated colloidal dispersions (coated silica-cyclohexane
      polydimethylsiloxane). The contact angle of the colloidal liquid-gas interface at
      a solid substrate (coated glass) was determined for a series of compositions.
      Upon approach to the critical point, a transition occurs from partial to complete
      wetting.

PMID- 12785959
TI  - Probing the lateral composition profile of self-assembled islands.
AB  - We apply a selective etching procedure to probe the lateral composition profile
      of self-assembled SiGe pyramids on a Si(001) substrate surface. We find that the
      pyramids consist of highly Si intermixed corners, whereas the edges, the apex,
      and the center of the pyramids remain Ge rich. Our results cannot be explained by
      existing growth models that minimize strain energy. We use a model that includes
      surface interdiffusion during island growth, underlining the paramount importance
      of surface processes during the formation of self-assembled quantum dot
      heterostructures in many different material systems.

PMID- 12785960
TI  - Distance dependence of the interaction between single atoms: gold dimers on
      NiAl(110).
AB  - The importance of substrate-mediated adsorbate-adsorbate interactions on
      electronic states has been demonstrated for Au dimers on NiAl(110) with a
      scanning tunneling microscope and density functional calculations. An unoccupied
      resonance observed in single Au atoms splits into a doublet in Au dimers. The
      energy splitting depends inversely on the distance between the two adatoms,
      revealing the relative importance of direct and substrate-mediated interactions.
      Spatially resolved conductance measurements of Au dimers reveal the symmetric and
      antisymmetric characters of the doublet states.

PMID- 12785961
TI  - One-dimensional instability in BaVS3.
AB  - The 3d(1) system BaVS3 undergoes a series of remarkable electronic phase
      transitions. We show that the metal-insulator transition at T(MI)=70 K is
      associated with a structural transition announced by a huge regime of one
      dimensional (1D) lattice fluctuations, detected up to 170 K. These 1D
      fluctuations correspond to a 2k(F)=c(*)/2 charge-density wave (CDW) instability
      of the d(z(2)) electron gas. We discuss the formation below T(MI) of an
      unconventional CDW state involving the condensation of the other V4+ 3d(1)
      electrons of the quasidegenerate e(t(2g)) orbitals. This study stresses the role
      of the orbital degrees of freedom in the physics of BaVS3 and reveals the
      inadequacy of current first principle band calculations to describe its
      electronic ground state.

PMID- 12785962
TI  - Field expulsion and reconfiguration in polaritonic photonic crystals.
AB  - We uncover a rich set of optical phenomena stemming from the incorporation of
      polar materials exhibiting transverse phonon polariton excitations into a
      photonic crystal structure. We identify in the frequency spectrum two regimes in
      which the dielectric response of the polaritonic medium can induce extreme
      localization of the electromagnetic energy. Our analysis of the effect of
      polarization and the interaction between the polariton and photonic band gaps on
      the Bloch states leads to a pair of mechanisms for sensitive frequency-controlled
      relocation and/or reconfiguration of the fields.

PMID- 12785963
TI  - Ferromagnetism and metal-insulator transition in the disordered Hubbard model.
AB  - A detailed study of the paramagnetic to ferromagnetic phase transition in the one
      band Hubbard model in the presence of binary-alloy disorder is presented. The
      influence of the disorder (with concentrations x and 1-x of the two alloy ions)
      on the Curie temperature T(c) is found to depend strongly on electron density n.
      While at high densities, n>x, the disorder always reduces T(c); at low densities,
      n<x, the disorder can even enhance T(c) if the interaction is strong enough. At
      the particular density n=x (i.e., not necessarily at half-filling) the interplay
      between disorder-induced band splitting and correlation induced Mott transition
      gives rise to a new type of metal-insulator transition.

PMID- 12785964
TI  - Failure of Russell-Saunders coupling in the 5f states of plutonium.
AB  - Using high energy-electron energy loss spectroscopy, transmission electron
      microscopy, and synchrotron-radiation-based x-ray absorption spectroscopy, we
      provide the first experimental evidence that Russell-Saunders (LS) coupling fails
      for the 5f states of Pu. These results support the assumption that only the use
      of jj or intermediate coupling is appropriate for the 5f states of Pu. High
      energy-electron energy loss spectroscopy experiments were performed by use of a
      transmission electron microscope and are coupled with image and diffraction data;
      therefore, the measurements are completely phase specific.

PMID- 12785965
TI  - Kondo effect in a few-electron quantum ring.
AB  - A small quantum ring with less than ten electrons was studied by transport
      spectroscopy. For strong coupling to the leads a Kondo effect is observed and
      used to characterize the spin structure of the system in a wide range of magnetic
      fields. At small magnetic fields Aharonov-Bohm oscillations influenced by Coulomb
      interaction appear. They exhibit phase jumps by pi at the Coulomb-blockade
      resonances. Inside Coulomb-blockade valleys the Aharonov-Bohm oscillations can
      also be studied due to the finite conductance caused by the Kondo effect.
      Astonishingly, the maxima of the oscillations show linear shifts with increasing
      magnetic field and gate voltage.

PMID- 12785966
TI  - Spin chirality fluctuations and anomalous Hall effect in itinerant ferromagnets.
AB  - The anomalous Hall effect due to the spin chirality order and fluctuation is
      studied theoretically in a Kondo lattice model without the relativistic spin
      orbit interaction. Even without the correlations of the localized spins,
      sigma(xy) can emerge depending on the lattice structure and the spin anisotropy.
      We reveal the condition for this chirality-fluctuation driven mechanism for
      sigma(xy). Our semiquantitative estimates for a pyrochlore oxide Nd2Mo2O7 give a
      finite sigma(xy) approximately equal 10 Omega(-1) cm(-1) together with a high
      resistivity rho(xx) approximately equal 10(-4)-10(-3) Omega cm, in agreement with
      experiments.

PMID- 12785967
TI  - Vertical friedel oscillations in interface-induced surface charge modulations of
      ultrathin quantum islands.
AB  - Two-dimensional Pb islands of a few atomic layers are grown on the incommensurate
      Si(111)-Pb surface at low temperatures. Among them, two types of islands having
      different stacking with the substrate are observed. These islands, respectively,
      display an alternating image contrast with their thickness. Besides, the
      contrasts of the islands of different types are complementary to each other layer
      by layer. These intriguing behaviors do not show significant bias dependence
      throughout the range from -3 to +3 V and can be explained by the vertical charge
      oscillation with the growth of a new layer. The charge oscillation in the out-of
      plane direction originates from electron scattering by the in-plane potential
      variation at the Pb/Si interface.

PMID- 12785968
TI  - Exact microscopic wave function for a topological quantum membrane.
AB  - The higher dimensional quantum Hall liquid constructed recently supports stable
      topological membrane excitations. Here we introduce a microscopic interacting
      Hamiltonian and present its exact ground state wave function. We show that this
      microscopic ground state wave function describes a topological quantum membrane.
      We also construct variational wave functions for excited states using the
      noncommutative algebra on the four sphere. Our approach introduces a
      nonperturbative method to quantize topological membranes.

PMID- 12785969
TI  - "Fingered" patterns in electron droplets in nonuniform magnetic fields.
AB  - A semiclassical analysis of a two-dimensional electron droplet in a high,
      nonuniform magnetic field predicts that the droplet will form "fingered" patterns
      upon increasing the number of electrons. We construct explicit examples of these
      patterns using methods first developed for the flow of two-dimensional viscous
      fluids. We complement our analytical results with Monte Carlo simulations of the
      droplet wave function, and find that at the point where the semiclassical
      analysis predicts a cusp on the interface, the droplet fissions-a type of
      "quantum breakup" phenomenon.

PMID- 12785970
TI  - Metal-induced gap states at well defined alkali-halide/metal interfaces.
AB  - In order to search for states specific to insulator/metal interfaces, we have
      studied epitaxially grown interfaces with element-selective near edge x-ray
      absorption fine structure. An extra peak is observed below the bulk edge onset
      for LiCl films on Cu and Ag substrates. The nature of chemical bonds as probed by
      x-ray photoemission spectroscopy and Auger electron spectroscopy remains
      unchanged, so we regard this as evidence for metal-induced gap states (MIGS)
      formed by the proximity to a metal, rather than local bonds at the interface. The
      dependence on the film thickness shows that the MIGS are as thin as one
      monolayer. An ab initio electronic structure calculation supports the existence
      of the MIGS that are strongly localized at the interface.

PMID- 12785971
TI  - Electronic structure of the YH3 phase from angle-resolved photoemission
      spectroscopy.
AB  - Yttrium can be loaded with hydrogen up to high concentrations causing dramatic
      structural and electronic changes of the host lattice. We report on angle
      resolved photoemission experiments of the Y trihydride phase. Most importantly,
      we find the absence of metal d bands at the Fermi level and a set of flat, H
      induced bands located at much higher binding energy than predicted, indicating an
      increased electron affinity at H sites.

PMID- 12785972
TI  - Search for E(2g) phonon modes in MgB2 single crystals by point-contact
      spectroscopy.
AB  - The electron-phonon interaction in magnesium diboride MgB2 single crystals is
      investigated by point-contact (PC) spectroscopy. For the first time the electron
      coupling with E(2g) phonon modes is resolved in the PC spectra. The correlation
      between intensity of the extremely broad E(2g) modes in the PC spectra and value
      of the superconducting gap is established. Our observations favor current
      theoretical models for electron-phonon mediated superconductivity in MgB2, and
      they better match the harmonic phonon model.

PMID- 12785973
TI  - Magnon heat transport in doped La2CuO4.
AB  - We present results of the thermal conductivity of La2CuO4 and La(1.8)Eu(0.2)CuO4
      single crystals which represent model systems for the two-dimensional spin-1/2
      Heisenberg antiferromagnet on a square lattice. We find large anisotropies of the
      thermal conductivity which are explained in terms of two-dimensional heat
      conduction by magnons within the CuO2 planes. Nonmagnetic Zn substituted for Cu
      gradually suppresses this magnon thermal conductivity kappa(mag). A semiclassical
      analysis of kappa(mag) is shown to yield a magnon mean free path which scales
      linearly with the reciprocal concentration of Zn ions.

PMID- 12785974
TI  - Antiferromagnetic vortex core in Tl(2)Ba(2)CuO(6+delta) studied by nuclear
      magnetic resonance.
AB  - Spatially resolved NMR is used to probe the magnetism in and around vortex cores
      of nearly optimally doped Tl(2)Ba(2)CuO(6+delta) (T(c)=85 K). The NMR relaxation
      rate T(-1)1 at the 205Tl site provides direct evidence that the antiferromagnetic
      (AF) spin correlation is significantly enhanced in the vortex core region. In the
      core region Cu spins show a local AF ordering with moments parallel to the layers
      at T(N)=20 K. Above T(N) the core region is in the paramagnetic state which is a
      reminiscence of the state above the pseudogap temperature (T(*) approximately 120
      K), indicating that the pseudogap disappears within cores.

PMID- 12785975
TI  - Field-induced thermal metal-to-insulator transition in underdoped La(2
      x)Sr(x)CuO(4+delta).
AB  - The transport of heat and charge in cuprates was measured in single crystals of
      La(2-x)Sr(x)CuO(4+delta) (LSCO) across the doping phase diagram at low
      temperatures. In underdoped LSCO, the thermal conductivity is found to decrease
      with increasing magnetic field in the T-->0 limit, in striking contrast to the
      increase observed in all superconductors, including cuprates at higher doping. In
      heavily underdoped LSCO, where superconductivity can be entirely suppressed with
      an applied magnetic field, we show that a novel thermal metal-to-insulator
      transition takes place upon going from the superconducting state to the field
      induced normal state.

PMID- 12785976
TI  - Fermi-liquid ground state in the n-type Pr(0.91)LaCe(0.09)CuO(4-y) copper-oxide
      superconductor.
AB  - We report nuclear magnetic resonance studies on the low-doped n-type copper-oxide
      Pr(0.91)LaCe(0.09)CuO(4-y) (T(c)=24 K) in the superconducting state and in the
      normal state uncovered by the application of a strong magnetic field. We find
      that when the superconductivity is removed the underlying ground state is the
      Fermi liquid state. This result is at variance with that inferred from previous
      thermal conductivity measurement and appears to contrast with that in p-type
      copper oxides with a similar doping level where high-T(c) superconductivity sets
      in within the pseudogap phase. The data in the superconducting state are
      consistent with the line-node gap model.

PMID- 12785977
TI  - Nanoengineered magnetic-field-induced superconductivity.
AB  - The perpendicular critical fields of a superconducting film have been strongly
      enhanced by using a nanoengineered lattice of magnetic dots (dipoles) on top of
      the film. Magnetic-field-induced superconductivity is observed in these hybrid
      superconductor/ferromagnet systems due to the compensation of the applied field
      between the dots by the stray field of the dipole array. By switching between
      different magnetic states of the nanoengineered field compensator, the critical
      parameters of the superconductor can be effectively controlled.

PMID- 12785978
TI  - Mott insulator to high Tc superconductor via pressure: resonating valence bond
      theory and prediction of new systems.
AB  - Mott insulator superconductor transition, via pressure and no external doping, is
      studied in orbitally nondegenerate spin-1 / 2 systems. It is presented as another
      resonating valence bond route to high T(c) superconductivity. We propose a
      "strong coupling" hypothesis that views long range Coulomb force driven first
      order Mott transition as a self-doping process that also preserves superexchange
      on the metal side. We present a two-species t-J model where conserved N0 doubly
      occupied (e(-)) sites and N0 empty sites (e(+)) hop in the background of N-2N(0)
      singly occupied (neutral) sites in a lattice of N sites. An equivalence to the
      regular t-J model is made. Some old and new systems are predicted to be
      candidates for pressure-induced high T(c) superconductivity.

PMID- 12785979
TI  - Colossal magnetoresistance in manganites as a multicritical phenomenon.
AB  - The colossal magnetoresistance in manganites AMnO3 is studied from the viewpoint
      of multicritical phenomena. To understand the complicated interplay of various
      phases, we study the Ginzburg-Landau theory in terms of both the mean-field
      approximation and the renormalization-group analysis for comparison with the
      observed phase diagram. Several novel features, such as the first-order
      ferromagnetic transition and the dip in the transition temperature near the
      multicritical point, can be understood as being driven by enhanced fluctuations
      near the multicritical point. Furthermore, we obtain a universal scaling relation
      for the H/M versus M2 plot (Arrott plot), which fits rather well with the
      experimental data, providing further evidence for the enhanced fluctuation.

PMID- 12785980
TI  - Drude weight at finite temperatures for some nonintegrable quantum systems in one
      dimension.
AB  - Using conformal perturbation theory, we show that, for some classes of the one
      dimensional quantum liquids that possess the Luttinger liquid fixed point in the
      low-energy limit, the Drude weight at finite temperatures is nonvanishing, even
      when the system is nonintegrable and the total current is not conserved. We also
      obtain the asymptotically exact low-temperature formula of the Drude weight for
      Heisenberg XXZ spin chains, which agrees quite well with recent numerical data.

PMID- 12785981
TI  - Nonmonotonic bias voltage dependence of the magnetocurrent in GaAs-based magnetic
      tunnel transistors.
AB  - Magnetic tunnel transistors are used to study spin-dependent hot electron
      transport in thin CoFe films and across CoFe/GaAs interfaces. The magnetocurrent
      observed when the orientation of a CoFe base layer moment is reversed relative to
      that of a CoFe emitter, is found to exhibit a pronounced nonmonotonic variation
      with electron energy. A model based on spin-dependent inelastic scattering in the
      CoFe base layer and strong electron scattering at the CoFe/GaAs interface,
      resulting in a broad electron angular distribution, can well account for the
      variation of the magnetocurrent in magnetic tunnel transistors with GaAs(001) and
      GaAs(111) collectors.

PMID- 12785982
TI  - Experimental observation of a nearly logarithmic decay of the orientational
      correlation function in supercooled liquids on the picosecond-to-nanosecond time
      scales.
AB  - Dynamics of five supercooled molecular liquids have been studied using optical
      heterodyne detected optical Kerr effect experiments. "Intermediate" time scale
      power law decays (approximately 2 ps to 1-10 ns) with temperature independent
      exponents close to -1 have been observed in all five samples from high
      temperature to approximately T(c), the mode-coupling theory (MCT) critical
      temperature. The amplitude of the intermediate power law increases with
      temperature as [(T-T(c))/T(c)](1/2). The results cannot be explained by standard
      MCT, and one possible explanation within MCT would require the higher order
      singularity scenario, thought to be highly improbable, to be virtually universal.

PMID- 12785983
TI  - Hydrogen local vibrational modes in zinc oxide.
AB  - Using Raman backscattering spectroscopy we have observed six local vibrational
      modes in as-grown state-of-the-art nominally undoped zinc oxide single crystals.
      The local vibrational modes are located at nu=2854, 2890, 2918, 2948, 2988, and
      3096 cm(-1). Some specimens were annealed up to 950 degrees C to remove hydrogen.
      A subsequent Raman backscattering measurement revealed that the local vibrational
      modes disappeared. This establishes that the observed local vibrational modes are
      caused by the presence of hydrogen in the ZnO crystals.

PMID- 12785984
TI  - Direct observation of localized second-harmonic enhancement in random metal
      nanostructures.
AB  - Second harmonic (SH) scanning optical microscopy in reflection is used to image
      the gold film surface covered with randomly placed scatterers. SH images obtained
      with a tightly focused tunable (750-830 nm) laser beam show small (approximately
      0.7 microm) and very bright (approximately 10(3) times the background) spots,
      whose locations depend on the wavelength and polarization of light. Comparing SH
      and fundamental harmonic (FH) images, we conclude that the localized SH
      enhancement occurs due to the overlap of FH and SH eigenmodes. The probability
      density function of the SH signal is found to follow the power-law dependence.

PMID- 12785985
TI  - Optimal multiqubit operations for Josephson charge qubits.
AB  - We introduce a method for finding the required control parameters for a quantum
      computer that yields the desired quantum algorithm without invoking elementary
      gates. We concentrate on the Josephson charge-qubit model, but the scenario is
      readily extended to other physical realizations. Our strategy is to numerically
      find any desired double- or triple-qubit gate. The motivation is the need to
      significantly accelerate quantum algorithms in order to fight decoherence.

PMID- 12785986
TI  - Polarization qubit phase gate in driven atomic media.
AB  - We present here an all-optical scheme for the experimental realization of a
      quantum phase gate. It is based on the polarization degree of freedom of two
      traveling single-photon wave packets and exploits giant Kerr nonlinearities that
      can be attained in coherently driven ultracold atomic media.

PMID- 12785987
TI  - Stochastic modeling approach to the incubation time of prionic diseases.
AB  - Transmissible spongiform encephalopathies are neurodegenerative diseases for
      which prions are the attributed pathogenic agents. A widely accepted theory
      assumes that prion replication is due to a direct interaction between the
      pathologic (PrP(Sc)) form and the host-encoded (PrP(C)) conformation, in a kind
      of autocatalytic process. Here we show that the overall features of the
      incubation time of prion diseases are readily obtained if the prion reaction is
      described by a simple mean-field model. An analytical expression for the
      incubation time distribution then follows by associating the rate constant to a
      stochastic variable log normally distributed. The incubation time distribution is
      then also shown to be log normal and fits the observed BSE (bovine spongiform
      encephalopathy) data very well. Computer simulation results also yield the
      correct BSE incubation time distribution at low PrP(C) densities.

PMID- 12785988
TI  - Possible test of the thermodynamic approach to granular media.
AB  - We study the steady state distribution of the energy of the Sherrington
      Kirkpatrick model driven by a tapping mechanism which mimics the mechanically
      driven dynamics of granular media. The dynamics consists of two phases: a zero
      temperature relaxation phase which leads the system to a metastable state, then a
      tapping which excites the system thus reactivating the relaxational dynamics.
      Numerically, we investigate whether the distribution of the energies of the
      blocked states obtained agrees with a simple canonical form of the Edwards
      measure. It is found that this canonical measure is in good agreement with the
      dynamically measured energy distribution. A possible experimental test of the
      Edwards measure based on the study here is proposed.

PMID- 12785990
TI  - Comment on "Electron spectral function and algebraic spin liquid for the normal
      state of underdoped high T(c) superconductors".

PMID- 12785989
TI  - What is the origin of chirality in the cholesteric phase of virus suspensions?
AB  - We report a study of the cholesteric phase in monodisperse suspensions of the
      rodlike virus fd sterically stabilized with the polymer polyethylene glycol
      (PEG). After coating the virus with neutral polymers, the phase diagram and
      nematic order parameter of the fd-PEG system then become independent of ionic
      strength. Surprisingly, the fd-PEG suspensions not only continue to exhibit a
      cholesteric phase, which means that the grafted polymer does not screen all
      chiral interactions between rods, but paradoxically the cholesteric pitch of this
      sterically stabilized fd-PEG system varies with ionic strength. Furthermore, we
      observe that the cholesteric pitch decreases with increasing viral contour
      length, in contrast to theories which predict the opposite trend. Different
      models of the origin of chirality in colloidal liquid crystals are discussed.

PMID- 12785992
TI  - Beliaev damping and Kelvin mode spectroscopy of a Bose-Einstein condensate in the
      presence of a vortex line.
AB  - It is demonstrated theoretically that the counter-rotating quadrupole mode in a
      vortex of Bose-Einstein condensates can decay into a pair of Kelvin modes via the
      Beliaev process. We calculate the spectral weight of a density-response function
      within the Bogoliubov framework, taking account of both Beliaev and Landau
      processes. Good agreement with experiment on 87 Rb by Bretin et al. [Phys. Rev.
      Lett., 100403 (2003)]] allows us to unambiguously identify the decayed mode as
      the Kelvin wave propagating along a vortex line.

PMID- 12785993
TI  - Metropolis importance sampling for rugged dynamical variables.
AB  - A funnel transformation is introduced, which acts recursively from higher towards
      lower temperatures. It biases the a priori probabilities of a canonical or
      generalized ensemble Metropolis simulation, so that they zoom in on the global
      energy minimum, if a funnel exists indeed. A first, crude approximation to the
      full transformation, called rugged Metropolis one (RM1), is tested for Met
      Enkephalin. At 300 K the computational gain is a factor of 2 and, due to its
      simplicity, RM1 is well suited to replace the conventional Metropolis updating
      for these kinds of systems.

PMID- 12785994
TI  - Single-file diffusion of atomic and colloidal systems: asymptotic laws.
AB  - We present a general derivation of the non-Fickian behavior for the self
      diffusion of identically interacting particle systems with excluded mutual
      passage. We show that the conditional probability distribution of finding a
      particle at position x(t) after time t, when the particle was located at x(0) at
      t=0, follows a Gaussian distribution in the long-time limit, with variance 2W(t)
      approximately t(1/2) for overdamped systems and with variance 2W(t) approximately
      t for classical systems. The asymptotic behavior of the mean-squared
      displacement, W(t), is shown to be independent of the nature of interactions for
      homogeneous systems in the fluid state. Moreover, the long-time behavior of self
      diffusion is determined by short-time and large-scale collective density
      fluctuations.

PMID- 12785995
TI  - Long-term evolution of stellar self-gravitating systems away from thermal
      equilibrium: connection with nonextensive statistics.
AB  - With particular attention to the recently postulated introduction of a
      nonextensive generalization of Boltzmann-Gibbs statistics, we study the long-term
      stellar dynamical evolution of self-gravitating systems on time scales much
      longer than the two-body relaxation time. In a self-gravitating N-body system
      confined in an adiabatic wall, we show that the quasiequilibrium sequence arising
      from the Tsallis entropy, so-called stellar polytropes, plays an important role
      in characterizing the transient states away from the Boltzmann-Gibbs equilibrium
      state.

PMID- 12785996
TI  - Decay of high-energy astrophysical neutrinos.
AB  - Existing limits on the nonradiative decay of one neutrino to another plus a
      massless particle (e.g., a singlet Majoron) are very weak. The best limits on the
      lifetime to mass ratio come from solar neutrino observations and are tau/m
      greater, similar 10(-4) s/eV for the relevant mass eigenstate(s). For lifetimes
      even several orders of magnitude longer, high-energy neutrinos from distant
      astrophysical sources would decay. This would strongly alter the flavor ratios
      from the phi(nu(e)):phi(nu(mu)):phi(nu(tau))=1:1:1 expected from oscillations
      alone and should be readily visible in the near future in detectors such as
      IceCube.

PMID- 12786001
TI  - Gluonic excitation of the three-quark system in SU(3) lattice QCD.
AB  - We present the first study of the gluonic excitation in the three-quark (3Q)
      system in SU(3) lattice QCD with beta=5.8 and 16(3) x 32 at the quenched level.
      For the spatially fixed 3Q system, we measure the gluonic excited-state
      potential, which is responsible for the properties of hybrid baryons. The lowest
      gluonic-excitation energy in the 3Q system is found to be about 1 GeV in the
      hadronic scale. This large gluonic-excitation energy is expected to bring about
      the success of the simple quark model without gluonic modes.

PMID- 12786000
TI  - Improved limits on nu(e) emission from mu+ decay.
AB  - We investigated mu(+) decays at rest produced at the ISIS beam stop target.
      Lepton flavor (LF) conservation has been tested by searching for nu(e) via the
      detection reaction p(nu(e),e(+))n. No nu(e) signal from LF violating mu(+) decays
      was identified. We extract upper limits of the branching ratio (BR) for the LF
      violating decay mu(+)-->e(+)+nu(e)+nu(-) compared to the standard model (SM)
      mu(+)-->e(+)+nu(e)+nu(mu) decay: BR<0.9(1.7) x 10(-3) (90% C.L.) depending on the
      spectral distribution of nu(e) characterized by the Michel parameter
      rho=0.75(0.0). These results improve earlier limits by one order of magnitude and
      restrict extensions of the SM in which nu(e) emission from mu(+) decay is allowed
      with considerable strength. The decay mu(+)-->e(+)+nu(e)+nu(mu) often proposed as
      a potential source for the nu(e) signal observed in the LSND experiment can be
      excluded.

PMID- 12785998
TI  - Branching fractions of tau leptons to three charged hadrons.
AB  - From electron-positron collision data collected with the CLEO detector operating
      at Cornell Electron Storage Ring near sqrt[s]=10.6 GeV, improved measurements of
      the branching fractions for tau decays into three explicitly identified hadrons
      and a neutrino are presented as B(tau(-)-->pi(-)pi(+)pi(-)nu(tau))=(9.13+/-0.05+/
      0.46)%, B(tau(-)-->K-pi(+)pi(-)nu(tau))=(3.84+/-0.14+/-0.38) x 10(-3), B(tau(-)-
      >K-K+pi(-)nu(tau))=(1.55+/-0.06+/-0.09) x 10(-3), and B(tau(-)-->K-K+K
      nu(tau))<3.7 x 10(-5) at 90% C.L., where the uncertainties are statistical and
      systematic, respectively.

PMID- 12786002
TI  - Anisotropic admixture in color-superconducting quark matter.
AB  - The analysis of color-superconducting two-flavor deconfined quark matter at
      moderate densities is extended to include a particular spin-1 Cooper pairing of
      those quarks which do not participate in the standard spin-0 diquark condensate.
      (i) The relativistic spin-1 gap delta(') implies spontaneous breakdown of
      rotation invariance manifested in the form of the quasifermion dispersion law.
      (ii) The critical temperature of the anisotropic component is approximately given
      by the relation T(')(c) approximately delta(')(T=0)/3. (iii) For massless
      fermions the gas of anisotropic Bogolyubov-Valatin quasiquarks becomes
      effectively gapless and two dimensional. Consequently, its specific heat depends
      quadratically on temperature. (iv) All collective Nambu-Goldstone excitations of
      the anisotropic phase have a linear dispersion law and the whole system remains a
      superfluid. (v) The system exhibits an electromagnetic Meissner effect.

PMID- 12786003
TI  - Production of energetic electrons in the process of photodetachment of F-.
AB  - An imaging technique is used to record an energy and angle resolved spectrum of
      electrons produced by photodetachment of F- in a strong infrared laser pulse. The
      spectrum involves contributions from more than 23 excess photon detachment
      channels. Its higher energy part extends beyond the classical cutoff value, and
      it appears as a pronounced plateau localized within a small angle along the laser
      polarization axis. A Keldysh-like theory is able to qualitatively reproduce the
      spectrum without taking into account the rescattering mechanism. The role of the
      parity of the initial bound state is discussed.

PMID- 12786004
TI  - Virtual-state formation in positron scattering from vibrating molecules: a
      gateway to annihilation enhancement.
AB  - In the present Letter, computational evidence is provided for the first time,
      choosing the polyatomic CH4 and C2H2 molecules as examples, of the existence of
      virtual states caused by dynamically coupling molecular vibrations with the
      positron motion during low-energy scattering processes. Our calculations provide
      lifetimes longer than vibrational periods, suggesting that the intermediate
      "compound" configurations could be the gateways through which the rate of
      annihilation of near-thermal positrons in molecular gases can become orders of
      magnitude larger than expected from the simpler dynamics, and as it is indeed
      observed experimentally.

PMID- 12786005
TI  - Spin-orbit quenching of positronium during atomic collisions.
AB  - When positrons are injected into a gas, 75% of the positronium (Ps) is likely to
      be formed as long-lived ortho-Ps. The main decay mechanisms for the ortho-Ps have
      been assumed to be natural decay of ortho-Ps and pickoff annihilation of the
      positron during Ps-atom collisions. A third possibility for annihilation is ortho
      Ps-->para-Ps conversion due to the spin-orbit interaction between the atom and
      colliding Ps. This extra quenching mechanism may explain a number of phenomena
      observed in the annihilation spectrum of Kr and Xe, including the very small Ps
      fraction of 3% seen for Xe.

PMID- 12786006
TI  - How to measure the phase diffusion dynamics in the micromaser.
AB  - We propose a realistic scheme for measuring the micromaser linewidth by
      monitoring the phase diffusion dynamics of the cavity field. Our strategy
      consists of exciting an initial coherent state with the same photon number
      distribution as the micromaser steady-state field, singling out a purely
      diffusive process in the system dynamics. After the injection of a counterfield,
      measurements of the population statistics of a probe atom allow us to derive the
      micromaser linewidth in all ranges of the relevant parameters, establishing
      experimentally the distinctive features of the micromaser spectrum due to the
      discreteness of the electromagnetic field.

PMID- 12786007
TI  - Spatial weak-light solitons in an electromagnetically induced nonlinear
      waveguide.
AB  - We show that a weak probe light beam can form spatial solitons in an
      electromagnetically induced transparency (EIT) medium composed of four-level
      atoms and a coupling light field. We find that the coupling light beam can induce
      a highly controllable nonlinear waveguide and exert very strong effects on the
      dynamical behavior of the solitons. Hence, in the EIT medium, it is not only
      possible to produce spatial solitons at very low light intensities but also
      simultaneously control these solitons by using the coupling-light-induced
      nonlinear waveguide.

PMID- 12786008
TI  - Controlling cohesive particle mixing and segregation.
AB  - We observe experimentally that particle systems that would otherwise mix can be
      made to segregate and vice versa simply by adding moisture. Using a newly
      developed theoretical approach, we generate phase diagrams that exhibit both
      mixed and segregated phases and show how the location of phase boundaries may be
      manipulated via modifying the mechanical and surface properties of the particles.
      These results have implications for industrial mixing/separation processes as
      well as novel particle production methods (e.g., engineered agglomerates with
      precisely prescribed compositions).

PMID- 12786010
TI  - Fracture of a viscous liquid.
AB  - When a viscous liquid hits a pool of liquid of the same nature, the impact region
      is hollowed by the shock. Its bottom becomes extremely sharp if increasing the
      impact velocity, and we report that the curvature at that place increases
      exponentially with the flow velocity, in agreement with a theory by Jeong and
      Moffatt. Such a law defines a characteristic velocity for the collapse of the
      tip, which explains both the cusplike shape of this region, and the instability
      of the cusp if increasing (slightly) the impact velocity. Then, a film of the
      upper phase is entrained inside the pool. We characterize the critical velocity
      of entrainment of this phase and compare our results with recent predictions by
      Eggers.

PMID- 12786009
TI  - Speckle visibility spectroscopy and variable granular fluidization.
AB  - We introduce a dynamic light scattering technique capable of resolving motion
      that changes systematically, and rapidly, with time. It is based on the
      visibility of a speckle pattern for a given exposure duration. Applying this to a
      vibrated layer of glass beads, we measure the granular temperature and its
      variation with phase in the oscillation cycle. We observe several transitions
      involving jammed states, where the grains are at rest during some portion of the
      cycle. We also observe a two-step decay of the temperature on approach to
      jamming.

PMID- 12786011
TI  - Observation of nonlinear frequency-sweeping suppression with rf diffusion.
AB  - Nonlinear frequency sweeping of unstable waves in a laboratory plasma is
      suppressed upon application of rf fields. Frequency sweeping is driven by a
      population of energetic electrons trapped in a magnetic dipole field that excite
      drift-resonant potential fluctuations and create coherent structures in phase
      space. Self-consistent numerical simulation reproduces the suppression and
      suggests an explanation due to rf scattering of energetic electrons that destroys
      the phase-space structures.

PMID- 12786012
TI  - Plasma expansion into a vacuum.
AB  - The charge separation effects in the collisionless plasma expansion into a vacuum
      are studied in great detail. Accurate results are obtained concerning the
      structure of the ion front, the resultant ion energy spectrum, and more
      specifically the maximum ion energy. These are of crucial importance for the
      interpretation of recent experiments, where high-energy ion jets were produced
      from short pulse interaction with solid targets.

PMID- 12786013
TI  - Weakly nonlinear theory for the ablative Rayleigh-Taylor instability.
AB  - A weakly nonlinear model is proposed for the Rayleigh-Taylor instability in the
      presence of ablation and thermal transport. The second harmonic generation
      efficiency of a single-mode disturbance is computed, as well as the nonlinear
      correction to the exponential growth of the fundamental modulation. Mode coupling
      in the spectrum of a multimode disturbance is thoroughly analyzed. The ablative
      stabilization can be clearly discussed because the derived formulas for the
      evanescent ablation rate are in agreement with previously known results for
      incompressible, inviscid, irrotational, and immiscible fluids [S. W. Haan, Phys.
      Fluids B 3, 2349 (1991)]; M. Berning and A. M. Rubenchik, Phys. Fluids 10, 1564
      (1998)]].

PMID- 12786014
TI  - Analytic solutions to the Vlasov equations for expanding plasmas.
AB  - The renormalization-group approach is applied to derive an exact solution to the
      self-consistent Vlasov kinetic equations for plasma particles in the quasineutral
      approximation. The solutions obtained describe three-dimensional adiabatic
      expansion of a plasma bunch with arbitrary initial velocity distributions of the
      electrons and ions. The solution found is illustrated by the examples on ion
      acceleration in a plasma with hot electrons and in a plasma with light impurity
      ions.

PMID- 12786015
TI  - Quiet-time statistics of electrostatic turbulent fluxes from the JET tokamak and
      the W7-AS and TJ-II stellarators.
AB  - The statistics of the quiet times between successive turbulent flux bursts
      measured at the edge of the JET tokamak and the W7-AS and TJ-II stellarators are
      analyzed in search for evidence of self-organized critical behavior. The results
      obtained are consistent with what would be expected in the situation where the
      underlying plasma is indeed in a near critical state.

PMID- 12786016
TI  - Zonal flows and transient dynamics of the L-H transition.
AB  - We elucidate the role of zonal flows in transient phenomena observed during L-H
      transition by studying a simple L-H transition model which contains the evolution
      of zonal flows, mean ExB flows, and the ion pressure gradient. Zonal flows are
      shown to trigger the L-H transition and cause time-transient behavior through the
      self-regulation of turbulence before a mean shearing, due to a steep pressure
      profile, secures a quiescent H mode. Surprisingly, this self-regulation lowers
      the power threshold for the ultimate transition to a quiescent H-mode state.

PMID- 12786017
TI  - Bound states of 3He at the edge of a 4He drop on a cesium surface.
AB  - We show that small amounts of 3He atoms, added to a 4He drop deposited on a flat
      cesium surface at zero temperature, populate bound states localized at the
      contact line. These edge states show up for drops large enough to develop well
      defined surface and bulk regions together with a contact line, and they are
      structurally different from the well-known Andreev states that appear at the free
      surface and at the liquid-solid interface of films. We illustrate the one-body
      density of 3He in a drop with 1000 4He atoms, and show that for a sufficiently
      large number of impurities the density profiles spread beyond the edge, coating
      both the curved drop surface and its flat base and eventually isolating it from
      the substrate.

PMID- 12785997
TI  - Measurement of the Cabibbo-Kobayashi-Maskawa matrix element V(ub) with B-->rhoenu
      decays.
AB  - We present a measurement of the branching fraction for the rare decays B-->rhoenu
      and extract a value for the magnitude of V(ub), one of the smallest elements of
      the Cabibbo-Kobayashi-Maskawa quark-mixing matrix. The results are given for five
      different calculations of form factors used to para-metrize the hadronic current
      in semileptonic decays. Using a sample of 55 x 10(6) BB meson pairs recorded with
      the BABAR detector at the PEP-II e(+)e(-) storage ring, we obtain B(B0-->rho(
      )e(+)nu)=(3.29+/-0.42+/-0.47+/-0.55) x 10(-4) and |V(ub)|=(3.64+/-0.22+/
      0.25(+0.39)(-0.56)) x 10(-3), where the uncertainties are statistical,
      systematic, and theoretical, respectively.

PMID- 12786018
TI  - Identification of the relative distribution of rare-earth ions in phosphate
      glasses.
AB  - The relative distribution of rare-earth ions R3+ (Dy3+ or Ho3+) in the phosphate
      glass RAl(0.30)P(3.05)O(9.62) was measured by employing the method of isomorphic
      substitution in neutron diffraction. It is found that 7.9(7) R-R nearest
      neighbors reside at 5.62(6) A in a network made from interlinked PO4 tetrahedra.
      Provided that the role of Al is explicitly considered, a self-consistent account
      of the local matrix atom correlations can be developed in which there are 1.68(9)
      bridging and 2.32(9) terminal oxygen atoms per phosphorus.

PMID- 12786019
TI  - Extreme superheating and supercooling of encapsulated metals in fullerenelike
      shells.
AB  - Nanometer-sized tin and lead crystals exhibit drastically altered melting and
      solidification behavior when encapsulated in fullerenelike graphitic shells. The
      melting transitions of encapsulated Sn and Pb nanocrystals are shown in an in
      situ electron microscopy study to occur at unexpectedly high temperatures,
      significantly higher than the melting point of the corresponding bulk materials.
      Atomistic simulations are used to show that the driving force for superheating is
      a pressure buildup of up to 3 GPa, that prevails inside graphitic shells under
      electron irradiation.

PMID- 12786021
TI  - Absence of 2kF splitting in the diffuse scattering from Cu3Au at the (001)
      surface.
AB  - We report a new type of short-range order correlations at the (001) surface of
      Cu3Au which no longer produces the 2k(F)-splitting characteristic for the bulk
      short-range order scattering. We present the temperature dependence of this
      phenomenon and a theoretical interpretation of its origin. We argue that this new
      surface effect is caused by a drastic change of the strain-induced interactions
      at the surface.

PMID- 12786020
TI  - X-ray scattering from freestanding polymer films with geometrically curved
      surfaces.
AB  - We show that the x-ray surface scattering from a freestanding polymer film
      exhibits features that cannot be explained by the usual stochastic formalism for
      surfaces with random height fluctuations. Instead, a geometric description of the
      film morphology assuming two curved surfaces characterized by a radius of
      curvature and a lateral cutoff length successfully accounts for the phase
      difference between the Kiessig fringes of the nominal "specular" and "off
      specular" components of the scattering. The formalism allows one to distinguish
      unambiguously between conformal and anticonformal curvature morphologies at long
      length scales.

PMID- 12786022
TI  - Solvent-induced symmetry breaking.
AB  - Symmetry breaking can be induced in a number of ways including interactions with
      a solvent. An example is the triiodide ion which is centrosymmetric in the gas
      phase. Molecular dynamics simulations of the triiodide ion in solution have been
      used to investigate the extent of symmetry breaking in a variety of solvents. We
      find that the triiodide ion loses its symmetry in water, ethanol, and methanol
      which form hydrogen bonds with the ion. This results in a localization of charge
      at one end of the ion and breaking of the geometric symmetry. The extent of
      symmetry breaking increases as the temperature is lowered. Correlation times for
      interconversion are reported and the energetics of symmetry breaking are
      presented. Analogies are made with second-order phase transitions.

PMID- 12786023
TI  - Self-limiting size distribution of supported cobalt nanoclusters at room
      temperature.
AB  - Formation of monodispersed Co nanoclusters on a single-crystal Si3N4 dielectric
      film at room temperature is reported. A remarkably narrow size distribution with
      the average size of approximately 30 Co atoms has been obtained. We have
      confirmed that the average size of Co nanoclusters is independent of the Co
      coverage and the cluster areal density linearly proportions to the Co deposition
      amount even at high coverages. Also, we have found that Co nanoclusters deposited
      on Si3N4 are thermally stable with respect to cluster aggregation/coalescence. We
      propose that this novel phenomenon is a quantum size effect, manifested by local
      energy minima in the electronic shell structure of Co quantum dots.

PMID- 12786024
TI  - Hydrogen incorporation in diamond: the nitrogen-vacancy-hydrogen complex.
AB  - We report the identification of the nitrogen-vacancy-hydrogen complex in a
      freestanding nitrogen-doped isotopically engineered single crystal diamond
      synthesized by chemical vapor deposition. The hydrogen atom is located in the
      vacancy of a nearest-neighbor nitrogen-vacancy defect and appears to be bonded to
      the nitrogen atom maintaining the trigonal symmetry of the center. The defect is
      observed by electron paramagnetic resonance in the negative charge state in
      samples containing a suitable electron donor (e.g., substitutional nitrogen
      N(0)(S)).

PMID- 12786025
TI  - Is there a glass transition in planar vortex systems?
AB  - The criteria for the existence of a glass transition in a planar vortex array
      with quenched disorder are studied. Applying a replica Bethe ansatz, we obtain
      for self-avoiding vortices the exact quenched average free energy and effective
      stiffness which is found to be in excellent agreement with recent numerical
      results for the related random bond dimer model [C. Zeng, P. L. Leath, and T.
      Hwa, Phys. Rev. Lett. 83, 4860 (1999)] Including a repulsive vortex interaction
      and a finite vortex persistence length xi, we find that for xi-->0 the system is
      at all temperatures in a glassy phase; a glass transition exists only for finite
      xi. Our results indicate that planar vortex arrays in superconducting films are
      glassy at presumably all temperatures.

PMID- 12785999
TI  - Study of the rare decays B0-->D((*)+)(s)pi(-) and B0-->D((*)-)(s)K+.
AB  - We report evidence for the decays B0-->D(+)(s)pi(-) and B0-->D(-)(s)K+ and the
      results of a search for B0-->D(*+)(s)pi(-) and B0-->D(*-)(s)K+ in a sample of 84
      x 10(6) upsilon(4S) decays into BB pairs collected with the BABAR detector at the
      PEP-II asymmetric-energy e(+)e(-) storage ring. We measure the branching
      fractions B(B0-->D(+)(s)pi(-))=[3.2+/-0.9(stat)+/-1.0(syst)] x 10(-5) and B(B0-
      >D(-)(s)K+)=[3.2+/-1.0(stat)+/-1.0(syst)] x 10(-5). We also set 90% C.L. limits
      B(B0-->D(*+)(s)pi(-))<4.1 x 10(-5) and B(B0-->D(*-)(s)K+)<2.5 x 10(-5).

PMID- 12786026
TI  - Transition structure at the Si(100)-SiO2 interface.
AB  - We characterize the transition structure at the Si(100)-SiO2 interface by
      addressing the inverse ion-scattering problem. We achieve sensitivity to Si
      displacements at the interface by carrying out ion-scattering measurements in the
      channeling geometry for varying ion energies. To interpret our experimental
      results, we generate realistic atomic-scale models using a first-principles
      approach and carry out ion-scattering simulations based on classical interatomic
      potentials. Silicon displacements larger than 0.09 A are found to propagate for
      three layers into the Si substrate, ruling out a transition structure with
      regularly ordered O bridges, as recently proposed.

PMID- 12786027
TI  - Localized molecular constraint on electron delocalization in a metallic chain.
AB  - An artificial quantum structure consisting of a single CO molecule adsorbed on a
      Au chain was assembled by manipulating single Au atoms on NiAl(110) at 12 K with
      a scanning tunneling microscope (STM). The CO disrupts the delocalization of
      electron density waves in the chain, as it suppresses the coupling between
      neighboring chain atoms. The possibility to specify the CO position on the chain
      allows controlled modification of the electronic properties in a quantum system.
      Inelastic electron tunneling spectroscopy with the STM provides vibrational
      characterization of the adsorbed CO.

PMID- 12786028
TI  - Reactive wetting: H2O/Rh(111).
AB  - First-principles calculations imply that neither H2O bilayers nor half
      dissociated, H2O+OH+H monolayers are thermodynamically stable on clean Rh(111).
      Thus, the experimental observation that Rh(111) supports a periodic 2D water
      adlayer needs an explanation. Chemistry involving common surface impurities,
      notably C atoms, may be the answer. Calculations show they provide favorable
      binding sites for H atoms detached from H2O. The resulting OH fragments can
      anchor a 2D water layer to the surface.

PMID- 12786029
TI  - Broken time-reversal symmetry in strongly correlated ladder structures.
AB  - We provide, for the first time, in a doped strongly correlated system (two-leg
      ladder), a controlled theoretical demonstration of the existence of a state in
      which long-range ordered orbital currents are arranged in a staggered pattern,
      coexisting with a charge density wave. The method used is the highly accurate
      density-matrix renormalization group technique. This brings us closer to recent
      proposals that this order is realized in the enigmatic pseudogap phase of the
      cuprate high temperature superconductors.

PMID- 12786030
TI  - Impurity absorption spectroscopy in 28Si: the importance of inhomogeneous isotope
      broadening.
AB  - We report high-resolution infrared absorption spectra of the neutral donors
      phosphorus and lithium, and the neutral acceptor boron, in isotopically pure 28Si
      crystals. Surprisingly, many of the transitions are much sharper than previously
      reported in natural Si. In particular, the 2p(0) line of phosphorus in 28Si has a
      full width at half maximum of only 4.2 microeV, about 5 times less than the
      narrowest 2p(0) line previously reported for natural Si, making it the narrowest
      shallow impurity transition yet observed. The widely held assumptions that the
      impurity transitions previously reported in high quality samples of natural Si
      revealed the true, homogeneous linewidths, are thus shown to be incorrect. The
      sharper transitions in 28Si also reveal new substructures in the boron and
      lithium spectra.

PMID- 12786031
TI  - Prominent quasiparticle peak in the photoemission spectrum of the metallic phase
      of V2O3.
AB  - We present the first observation of a prominent quasiparticle peak in the
      photoemission spectrum of the metallic phase of V2O3 and report new spectral
      calculations that combine the local-density approximation with the dynamical mean
      field theory (using quantum Monte Carlo simulations) to show the development of
      such a distinct peak with decreasing temperature. The experimental peak width and
      weight are significantly larger than in the theory.

PMID- 12786032
TI  - Electronic structure of oxygen dangling bond in glassy SiO2: the role of
      hyperconjugation.
AB  - The electronic structure and the nature of optical transitions in oxygen dangling
      bond in silica glass, the nonbridging oxygen hole center (NBOHC), were
      calculated. The calculation reproduced well the peak positions and oscillator
      strengths of the well-known optical absorption bands at 2.0 and 4.8 eV, and of
      the recently discovered absorption band at 6.8 eV. The 2.0 eV band was attributed
      to transition from the sigma bond between Si and dangling oxygen to nonbonding pi
      orbital on the dangling oxygen. The uniquely small electron-phonon coupling
      associated with the 2.0 eV transition is explained by stabilization of Si-O bond
      in the excited state by hyperconjugation effects.

PMID- 12786033
TI  - Quantum phase transition in quasi-one-dimensional BaRu6O12.
AB  - We report the first systematic study of the electrical transport and magnetic
      properties of BaRu6O12, which has a quasi-one-dimensional (quasi-1D) hollandite
      structure. We show that BaRu6O12 is quasi-1D electronically as well. Its physical
      properties were found to be extremely sensitive to disorder. Furthermore, a
      transition from being metallic with a resistance drop around 2 K to being weakly
      insulating as the applied magnetic field was increased was also found. We propose
      that these two features are related to the possible presence of a quantum phase
      transition in this material system.

PMID- 12786034
TI  - Resonant inversion of tunneling magnetoresistance.
AB  - Resonant tunneling via localized states in the barrier can invert
      magnetoresistance in magnetic tunnel junctions. Experiments performed on
      electrodeposited Ni/NiO/Co nanojunctions of area smaller than 0.01 microm(2) show
      that both positive and negative values of magnetoresistance are possible.
      Calculations based on Landauer-Buttiker theory explain this behavior in terms of
      disorder-driven statistical variations in magnetoresistance with a finite
      probability of inversion due to resonant tunneling.

PMID- 12786035
TI  - Optical detection of the Aharonov-Bohm effect on a charged particle in a
      nanoscale quantum ring.
AB  - We study spectroscopically the current produced by a charged particle moving in a
      nanosize semiconductor quantum ring subject to a perpendicular magnetic field.
      Several Aharonov-Bohm oscillations are observed in the emission of a charged
      exciton confined in a single ring structure. The magnetic field period of the
      oscillations correlates well with the size of the rings.

PMID- 12786036
TI  - Hexagonal and square flux line lattices in CeCoIn5.
AB  - Using small-angle neutron scattering, we have imaged the magnetic flux line
      lattice (FLL) in the d-wave heavy-fermion superconductor CeCoIn5. At low fields
      we find a hexagonal FLL. Around 0.6 T this undergoes what is most likely a first
      order transition to square symmetry, with the nearest neighbors oriented along
      the gap node directions. This orientation of the square FLL is consistent with
      theoretical predictions based on the d-wave order parameter symmetry.

PMID- 12786037
TI  - Weak-field thermal hall conductivity in the mixed state of d-wave
      superconductors.
AB  - Thermal transport in the mixed state of a d-wave superconductor is considered
      within the weak-field regime. We express the thermal conductivity, kappa(xx), and
      the thermal Hall conductivity, kappa(xy), in terms of the cross section for
      quasiparticle scattering from a single vortex. Solving for the cross section
      (neglecting the Berry phase contribution and the anisotropy of the gap nodes), we
      obtain kappa(xx)(H,T) and kappa(xy)(H,T) in surprisingly good agreement with the
      qualitative features of the experimental results for YBa2Cu3O6.99. In particular,
      we show that the simple, yet previously unexpected, weak-field behavior,
      kappa(xy)(H,T) approximately T squareroot [H], is that of thermally excited nodal
      quasiparticles, scattering primarily from impurities, with a small skew component
      provided by vortex scattering.

PMID- 12786038
TI  - ab plane ac conductivity in the cuprates: pseudogap effects below Tc.
AB  - Building on our understanding of the superfluid density rho(s)(T), we show how
      the pseudogap enters the in-plane optical conductivity sigma(omega,T) for
      temperatures T</=T(c). Signatures in sigma(omega,T) associated with competing
      proposals of a "hidden order" and "superconducting" origin for the pseudogap
      differ in their qualitative omega,T dependences. For the latter case, as T
      increases from 0, Re sigma(omega) is enhanced at high and low frequencies. We
      discuss these theories in light of current experiments.

PMID- 12786039
TI  - Increasing d-wave superconductivity by on-site repulsion.
AB  - We study, through the variational Monte Carlo technique, an extended Hubbard
      model away from half filled band density which contains two competing nearest
      neighbor interactions: a superexchange J favoring d-wave superconductivity and a
      repulsion V opposing it. We find that the on-site repulsion U effectively
      enhances the strength of J while suppressing that of V, thus favoring
      superconductivity. This result shows that attractions which do not involve charge
      fluctuations are very well equipped against strong electron-electron repulsion so
      much to get advantage from it.

PMID- 12786041
TI  - Carbon nanowire made of a long linear carbon chain inserted inside a multiwalled
      carbon nanotube.
AB  - A new type of one-dimensional (1D) carbon structure, carbon nanowires (CNWs), was
      discovered in the cathode deposits prepared by hydrogen arc discharge evaporation
      of carbon rods. Observation of high-resolution transmission electron microscopy
      (HRTEM) indicates that a CNW consists of a multiwalled carbon nanotube (MWNT)
      with a long 1D linear carbon chain (C chain) inserted into its innermost tube of
      0.7 nm in diameter. The characteristic Raman peaks of CNWs appeared at around
      1850 cm(-1). Raman scattering and HRTEM studies show the formation of a long
      linear C chain involving more than 100 carbon atoms inside a MWNT. This novel 1D
      carbon allotrope has potential applications in nanoelectronics, nanomechanics,
      and nanomaterials.

PMID- 12786040
TI  - Soft X-ray resonant magnetic diffraction.
AB  - We have conducted the first soft x-ray diffraction experiments from a bulk single
      crystal, studying the bilayer manganite La2-2xSr1+2xMn2O7 with x=0.475 in which
      we were able to access the (002) Bragg reflection using soft x rays. The Bragg
      reflection displays a strong resonant enhancement at the L(III) and L(II)
      manganese absorption edges. We demonstrate that the resonant enhancement of the
      magnetic diffraction of the (001) is extremely large, indeed so large that it
      exceeds that of the nonresonant Bragg diffraction. Resonant soft x-ray scattering
      of 3d transition metal oxides is the only technique for the atomic selective
      measurement of spin, charge, and orbital correlations in materials, such as high
      temperature superconductors, colossal magnetoresistance manganites, and charge
      stripe nickelates.

PMID- 12786042
TI  - Dynamic exchange coupling in magnetic bilayers.
AB  - A long-range dynamic interaction between ferromagnetic films separated by normal
      metal spacers is reported, which is communicated by nonequilibrium spin currents.
      It is measured by ferromagnetic resonance and explained by an adiabatic spin-pump
      theory. In such a resonance the spin-pump mechanism of spatially separated
      magnetic moments leads to an appreciable increase in the resonant linewidth when
      the resonance fields are well apart, and results in a dramatic linewidth
      narrowing when the resonant fields approach each other.

PMID- 12786043
TI  - Energy landscape theory, funnels, specificity, and optimal criterion of
      biomolecular binding.
AB  - We study the nature of biomolecular binding. We found that in general there
      exists several thermodynamic phases: a native binding phase, a non-native phase,
      and a glass or local trapping phase. The quantitative optimal criterion for the
      binding specificity is found to be the maximization of the ratio of the binding
      transition temperature versus the trapping transition temperature, or
      equivalently the ratio of the energy gap of binding between the native state and
      the average non-native states versus the dispersion or variance of the non-native
      states. This leads to a funneled binding energy landscape.

PMID- 12786044
TI  - Fitness distributions in exponentially growing asexual populations.
AB  - We explore a mean-field model for the evolution of exponentially growing
      populations of mutating replicators. Motivated by recent in vitro experiments
      devised to analyze phenotypic properties of bacterial and viral populations
      subjected to serial population transfers, we allow our in silico individuals to
      undergo unrestricted growth before applying bottleneck events. Different
      dynamical regimes of our model can be mapped to different experimental
      situations. Numerical and analytical results for fitness distributions calculated
      at the statistically stationary states of the dynamics compare favorably with
      available experimental data. Our model and results provide a common framework to
      better understand populations evolving under different selection pressures.

PMID- 12786045
TI  - Counterion distribution around DNA probed by solution X-ray scattering.
AB  - Counterion atmospheres condensed onto charged biopolymers strongly affect their
      physical properties and biological functions, but have been difficult to quantify
      experimentally. Here, monovalent and divalent counterion atmospheres around DNA
      double helices in solution are probed using small-angle x-ray scattering
      techniques. Modulation of the ion scattering factors by anomalous (resonant) x
      ray scattering and by interchanging ion identities yields direct measurements of
      the scattering signal due to the spatial correlation of surrounding ions to the
      DNA. The quality of the data permit, for the first time, quantitative tests of
      extended counterion distributions calculated from atomic-scale models of
      biologically relevant molecules.

PMID- 12786047
TI  - Microstructure and dynamics near an attractive colloidal glass transition.
AB  - The microstructure and dynamics of a colloidal system interacting via short
      ranged interparticle potential is studied by ultra-small-angle x-ray scattering
      and x-ray photon correlation spectroscopy. A colloidal gas-liquid type transition
      is induced when the short-ranged attractive interactions attain sufficient
      magnitude. The development of liquidlike structure is preceded by a systematic
      transition in the particle dynamics from diffusive to constrained motion and then
      completely frozen behavior. This demonstrates the existence of a jamming
      transition induced by strong short-ranged attractive interactions even at low
      packing fractions.

PMID- 12786049
TI  - Power-law time distribution of large earthquakes.
AB  - We study the statistical properties of time distribution of seismicity in
      California by means of a new method of analysis, the diffusion entropy. We find
      that the distribution of time intervals between a large earthquake (the main
      shock of a given seismic sequence) and the next one does not obey Poisson
      statistics, as assumed by the current models. We prove that this distribution is
      an inverse power law with an exponent mu=2.06+/-0.01. We propose the long-range
      model, reproducing the main properties of the diffusion entropy and describing
      the seismic triggering mechanisms induced by large earthquakes.

PMID- 12786046
TI  - Electron attachment to uracil: effective destruction at subexcitation energies.
AB  - We demonstrate that electrons at energies below the threshold for electronic
      excitation (<3 eV) effectively decompose gas phase uracil generating a mobile
      hydrogen radical and the corresponding closed shell uracil fragment anion (U-H)(
      ). The reaction is energetically driven by the large electron affinity of the (U
      H) radical. This observation has significant consequences for the molecular
      picture of radiation damage, i.e., genotoxic effects or damage of living cells
      due to the secondary component of high energy radiation.

PMID- 12786050
TI  - Singularities and spatial fluctuations in submonolayer epitaxy.

PMID- 12786052
TI  - Comment on "Freezing by heating in a driven mesoscopic system".

PMID- 12786048
TI  - Simple chemomechanical process for self-generation of rhythms and forms.
AB  - We show that cross-coupling between the geometrical changes and the chemical
      reaction-diffusion regimes within a piece of gel embedded in a stationary
      reactive medium kept far from equilibrium can destabilize the trivial steady
      state and lead to spatiotemporal dissipative structures. The involved physical
      processes are the spatial bistability and the swelling properties of the gel. As
      an illustration of this morphogenetic process, we show that a sphere of gel
      immersed within such a medium with autocatalytic properties can exhibit periodic
      radius pulsations, the amplitude of which are controlled by chemistry.

PMID- 12786053
TI  - Comment on "Total energy method from many-body formulation".

PMID- 12786055
TI  - Three-wave mixing of bogoliubov quasiparticles in a bose-einstein condensate.
AB  - A dressed basis is used to calculate the dynamics of three-wave mixing between
      Bogoliubov quasiparticles in a Bose condensate. Because of the observed
      oscillations between different momentum modes, an energy splitting, analogous to
      the optical Mollow triplet, appears in the Beliaev damping spectrum of the
      excitations from the oscillating modes.

PMID- 12786056
TI  - Efimov states in a Bose-Einstein condensate near a Feshbach resonance.
AB  - Recent experiments with Bose-Einstein condensates of 85Rb atoms near a Feshbach
      resonance have produced evidence for a condensate of diatomic molecules
      coexisting with the atom condensate. It should also be possible to create
      condensates of the triatomic molecules predicted by Efimov coexisting with the
      atom and dimer condensates. The smoking gun for the trimer condensate would be
      oscillatory dependence of observables on the binding energy of the trimer. It may
      also be possible to deduce the existence of the trimer condensate from the
      spectra of the bursts of atoms and dimers created in the disappearance of the
      trimers.

PMID- 12786057
TI  - Bose-Fermi mixtures in one dimension.
AB  - We analyze the phase stability and the response of a mixture of bosons and spin
      polarized fermions in one dimension (1D). Unlike in 3D, phase separation happens
      for low fermion densities. The dynamics of the mixture at low energy is
      independent of the spin-statistics of the components, and the modes are
      essentially undamped.

PMID- 12786058
TI  - Nonlinear evolution of quantum states in the adiabatic regime.
AB  - We investigate adiabatic evolution of quantum states as governed by the nonlinear
      Schrodinger equation and provide examples of applications with a nonlinear
      tunneling model for Bose-Einstein condensates. Our analysis not only spells out
      conditions for adiabatic evolution of eigenstates but also characterizes the
      motion of noneigenstates which cannot be obtained from the former in the absence
      of the superposition principle. We find that Aharonov-Anandan phases play the
      role of classical canonical actions and are conserved in the adiabatic evolution
      of noneigenstates.

PMID- 12786059
TI  - Observation of long-lived vortex aggregates in rapidly rotating Bose-Einstein
      condensates.
AB  - We study the formation of large vortex aggregates in a rapidly rotating dilute
      gas Bose-Einstein condensate. When we remove atoms from the rotating condensate
      with a tightly focused, resonant laser, the density can be locally suppressed,
      while fast circulation of a ring-shaped superflow around the area of suppressed
      density is maintained. Thus a giant vortex core comprising 7 to 60 phase
      singularities is formed. The giant core is only metastable, and it will refill
      with distinguishable single vortices after many rotation cycles. The surprisingly
      long lifetime of the core can be attributed to the influence of strong Coriolis
      forces in the condensate. In addition we have been able to follow the precession
      of off-center giant vortices for more than 20 cycles.

PMID- 12786060
TI  - Nonlinear electromagnetic X waves.
AB  - Nonlinear optical media that are normally dispersive support a new type of
      localized (nondiffractive and nondispersive) wave packets that are X shaped in
      space and time and have slower than exponential decay. High-intensity X waves,
      unlike linear ones, can be formed spontaneously through a trigger mechanism of
      conical emission, thus playing an important role in experiments.

PMID- 12786061
TI  - Levy flights in inhomogeneous media.
AB  - We investigate the impact of external periodic potentials on superdiffusive
      random walks known as Levy flights and show that even strongly superdiffusive
      transport is substantially affected by the external field. Unlike ordinary random
      walks, Levy flights are surprisingly sensitive to the shape of the potential
      while their asymptotic behavior ceases to depend on the Levy index mu. Our
      analysis is based on a novel generalization of the Fokker-Planck equation
      suitable for systems in thermal equilibrium. Thus, the results presented are
      applicable to the large class of situations in which superdiffusion is caused by
      topological complexity, such as diffusion on folded polymers and scale-free
      networks.

PMID- 12786062
TI  - New universality class for the three-dimensional XY model with correlated
      impurities: application to 4He in aerogels.
AB  - Encouraged by experiments on 4He in aerogels, we confine planar spins in the
      pores of simulated aerogels (diffusion limited cluster-cluster aggregation) in
      order to study the effect of quenched disorder on the critical behavior of the
      three-dimensional XY model. Monte Carlo simulations and finite-size scaling are
      used to determine critical couplings K(c) and exponents. In agreement with
      experiments, clear evidence of change in the thermal critical exponents nu and
      alpha is found at nonzero volume fractions of impurities. These changes are
      explained in terms of hidden long-range correlations within disorder
      distributions.

PMID- 12786063
TI  - Quantum stabilization in anharmonic crystals.
AB  - For a model of interacting quantum particles of mass m oscillating in a double
      well crystalline field, a mechanism of its stabilization by quantum effects is
      described. In particular, a stability condition involving m, the interaction
      intensity, and the parameters of the crystalline field is given. It is
      independent of the temperature and is satisfied if m is small enough and/or the
      tunneling frequency is big enough. It is shown that under this condition the
      infinite-volume free energy density is an analytic function of the external field
      and the displacement-displacement correlation function decays exponentially;
      hence, no phase transitions can arise at all temperatures. This gives a complete
      and rigorous answer to the question about the influence of quantum effects on
      structural phase transitions, the discussion of which was initiated in [T.
      Schneider, H. Beck, and E. Stoll, Phys. Rev. B 13, 1123 (1976)]].

PMID- 12786064
TI  - Quantum extension of the Jarzynski relation: analogy with stochastic dephasing.
AB  - The relation between the distribution of work performed on a classical system by
      an external force switched on an arbitrary time scale and the corresponding
      equilibrium free energy difference is generalized to quantum systems. Using the
      adiabatic representation, we show that this relation holds for isolated systems
      as well as for systems coupled to a bath described by a master equation. A close
      formal analogy is established between the present "classical trajectory" picture
      over populations of adiabatic states and phase fluctuations (dephasing) of a
      quantum coherence in spectral line shapes, described by the stochastic Liouville
      equation.

PMID- 12786065
TI  - Global charges of stationary non-Abelian black holes.
AB  - We consider stationary axially symmetric black holes in SU(2) Einstein-Yang-Mills
      dilaton theory. We present a mass formula for these stationary non-Abelian black
      holes, which also holds for Abelian black holes. The presence of the dilaton
      field allows for rotating black holes, which possess nontrivial electric and
      magnetic gauge fields, but do not carry a non-Abelian charge. We further present
      a new uniqueness conjecture.

PMID- 12786066
TI  - Initial data for black holes and black strings in 5D.
AB  - We explore time-symmetric hypersurfaces containing apparent horizons of black
      objects in a 5D spacetime with one coordinate compactified on a circle. We find a
      phase transition within the family of such hypersurfaces: the horizon has
      different topology for different parameters. The topology varies from S3 to S2 x
      S1. This phase transition is discontinuous--the topology of the horizon changes
      abruptly. We explore the behavior around the critical point and present a
      possible phase diagram.

PMID- 12786069
TI  - Evanescent-wave trapping and evaporative cooling of an atomic gas at the
      crossover to two dimensions.
AB  - A dense gas of cesium atoms at the crossover to two dimensions is prepared in a
      highly anisotropic surface trap that is realized with two evanescent light waves.
      Temperatures as low as 100 nK are reached with 20,000 atoms at a phase-space
      density close to 0.1. The lowest quantum state in the tightly confined direction
      is populated by more than 60%. The system provides atoms at a mean distance from
      the surface as low as 1 microm, and offers intriguing prospects for future
      experiments on degenerate quantum gases in two dimensions.

PMID- 12786067
TI  - Search for nu(e) from the sun at Super-Kamiokande-I.
AB  - We present the results of a search for low energy nu(e) from the Sun using 1496
      days of data from Super-Kamiokande-I. We observe no significant excess of events
      and set an upper limit for the conversion probability to nu(e) of the 8B solar
      neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's
      neutrino flux for total energy=8-20 MeV. We also set a flux limit for
      monochromatic nu(e) for E(nu(e))=10-17 MeV.

PMID- 12786070
TI  - Resonant double excitation observed in the near-threshold evolution of the
      photoexcited F K alpha satellite intensity in NaF.
AB  - We present a precise measurement of the photoexcited F K alpha satellite
      intensity's evolution for NaF from [1s2p] double excitation threshold to
      saturation. A direct comparison between the observed evolution and the x-ray
      absorption spectrum was successfully made, and the contribution of multielectron
      transitions to the absorption spectrum was clearly resolved for the first time. A
      resonance-like feature observed in the near-threshold evolution is attributed to
      the [1s2p]3p(2) resonant double excitation as confirmed by calculations.

PMID- 12786071
TI  - Drastic facilitation of the onset of global chaos.
AB  - We show that the onset of global chaos in a time periodically perturbed
      Hamiltonian system may occur at unusually small magnitudes of perturbation if the
      unperturbed system possesses more than one separatrix. The relevant scenario is
      the combination of the overlap in the phase space between resonances of the same
      order and their overlap in energy with chaotic layers associated with
      separatrices of the unperturbed system. We develop the asymptotic theory and
      verify it in simulations.

PMID- 12786072
TI  - Fingerprints of determinism in an apparently stochastic corrosion process.
AB  - We detect hints of determinism in an apparently stochastic corrosion problem.
      This experimental system has industrial relevance as it mimics the corrosion
      processes of pipelines transporting water, hydrocarbons, or other fuels to remote
      destinations. We subject this autonomous system to external periodic
      perturbations. Keeping the amplitude of the superimposed perturbations constant
      and varying the frequency, the system's response is analyzed. It reveals the
      presence of an optimal forcing frequency for which maximal response is achieved.
      These results are consistent with those for a deterministic system and indicate a
      classical resonance between the forcing signal and the autonomous dynamics.
      Numerical studies using a generic corrosion model are carried out to complement
      the experimental findings.

PMID- 12786073
TI  - Determination of limit cycles for strongly nonlinear oscillators.
AB  - An innovative approach to finding limit cycles is proposed and illustrated on the
      van der Pol equation. The technique developed in this Letter is similar to the
      Ritz's method in variational theory. The present theory can be applied to not
      only weakly nonlinear equations, but also strongly nonlinear ones, and the
      obtained results are valid for the whole solution domain.

PMID- 12786068
TI  - Narrowing of the balance function with centrality in Au+Au collisions at the
      square root of SNN = 130 GeV.
AB  - The balance function is a new observable based on the principle that charge is
      locally conserved when particles are pair produced. Balance functions have been
      measured for charged particle pairs and identified charged pion pairs in Au+Au
      collisions at the square root of SNN = 130 GeV at the Relativistic Heavy Ion
      Collider using STAR. Balance functions for peripheral collisions have widths
      consistent with model predictions based on a superposition of nucleon-nucleon
      scattering. Widths in central collisions are smaller, consistent with trends
      predicted by models incorporating late hadronization.

PMID- 12786074
TI  - Low-frequency behavior of beads constrained on a lattice.
AB  - We study sound propagation in a triangular lattice of spherical beads under
      isotropic stress. Polydispersity of real beads breaks some contacts, creating a
      disordered lattice of contacting beads. At large stress, the sound velocity
      behaves according to Hertz contact law and departs from it at lower stress. This
      evolution is reversible, with the same crossover when increasing or decreasing
      the stress, for a given piling. Correlations are much more sensitive to disorder.
      When calculated with signals propagated in the same lattice, they evolve
      reversibly with the stress, being much higher at large stress when the contact
      lattice is more regular. This leads to an interpretation of the non-Hertzian
      behavior in terms of progressive activation of contacts, in discrepancy with
      previous models involving buckling of force chains.

PMID- 12786075
TI  - Nonlinear magnetic induction by helical motion in a liquid sodium turbulent flow.
AB  - We report an experimental study of the magnetic field B--> induced by a turbulent
      swirling flow of liquid sodium submitted to a transverse magnetic field B-->(0).
      We show that the induced field can behave nonlinearly as a function of the
      magnetic Reynolds number, R(m). At low R(m), the induced mean field along the
      axis of the flow, <Bx>, and the one parallel to B-->(0), <B(y)>, first behave
      like R(2)(m), whereas the third component, <B(z)>, is linear in R(m). The sign of
      <Bx> is determined by the flow helicity. At higher R(m), B--> strongly depends on
      the local geometry of the mean flow: <Bx> decreases to zero in the core of the
      swirling flow but remains finite outside. We compare the experimental results
      with the computed magnetic induction due to the mean flow alone.

PMID- 12786076
TI  - Propagation instabilities of high-intensity laser-produced electron beams.
AB  - Measurements of energetic electron beams generated from ultrahigh intensity laser
      interactions (I>10(19) W/cm(2)) with dense plasmas are discussed. These
      interactions have been shown to produce very directional beams, although with a
      broad energy spectrum. In the regime where the beam density approaches the
      density of the background plasma, we show that these beams are unstable to
      filamentation and "hosing" instabilities. Particle-in-cell simulations also
      indicate the development of such instabilities. This is a regime of particular
      interest for inertial confinement fusion applications of these beams (i.e., "fast
      ignition").

PMID- 12786077
TI  - Demonstration of spectrally resolved x-ray scattering in dense plasmas.
AB  - We present the first spectrally resolved x-ray scattering measurements from solid
      density plasmas. The scattering spectra show the broadened Compton down-shifted
      feature allowing us to determine the electron temperature and density with high
      accuracy. In the low temperature limit, our data indicate that the ionization
      balance reflects the electrons in the conduction band consistent with
      calculations that include quantum mechanical corrections to the interaction
      potential.

PMID- 12786078
TI  - Vacancy excitation spectrum in solid 4He and longitudinal phonons.
AB  - The first microscopic ab initio calculation of the excitation spectrum of a
      vacancy in solid 4He is reported. The energy-wave vector dispersion relation has
      been obtained at melting density within a development of the shadow wave function
      variational technique. The calculation of the excitation spectrum of a vacancy
      gives a bandwidth which ranges from 6 to 10 K in the hcp solid 4He, depending on
      the particular direction of the wave vector of the excitation. The effective mass
      of the vacancy turns out to be about 0.35 4He masses. We have also computed the
      spectrum of longitudinal phonons and we find rather good agreement with recent
      experimental results.

PMID- 12786079
TI  - Three-dimensional imaging of microstructure in Au nanocrystals.
AB  - X-ray diffraction using a coherent beam involves the mutual interference among
      all the extremities of small crystals. The continuous diffraction pattern so
      produced can be phased because it can be oversampled. We have thus obtained three
      dimensional images of the interiors of Au nanocrystals that show 50 nm wide bands
      of contrast with [111] orientation that probably arise from internal twinning by
      dynamic recrystallization during their formation at high temperature.

PMID- 12786080
TI  - Quasistatic x-ray speckle metrology of microscopic magnetic return-point memory.
AB  - We have used coherent, resonant, x-ray magnetic speckle patterns to measure the
      statistical evolution of the microscopic magnetic domains in perpendicular
      magnetic films as a function of the applied magnetic field. Our work constitutes
      the first direct, ensemble-averaged study of microscopic magnetic return-point
      memory, and demonstrates the profound impact of interfacial roughness on this
      phenomenon. At low fields, the microscopic magnetic domains forget their past
      history with an exponential field dependence.

PMID- 12786081
TI  - Raman spectroscopy of hot dense hydrogen.
AB  - High P-T Raman measurements of solid and fluid hydrogen to above 1100 K at 70 GPa
      and to above 650 K in 150 GPa range, conditions previously inaccessible by static
      compression experiments, provide new insight into the behavior of the material
      under extreme conditions. The data give a direct measure of the melting curve
      that extends previous optical investigations by up to a factor of 4 in pressure.
      The magnitude of the vibron frequency temperature derivative (dnu/dT)(P)
      increases by a factor of approximately 30 over the measured pressure range,
      indicating an increase in intrinsic anharmonicity and weakening of the molecular
      bond.

PMID- 12786082
TI  - Test of the Einstein-Debye relation in supercooled dibutylphthalate at pressures
      up to 1.4 GPa.
AB  - Broadband dielectric measurements were carried out on di-n-butyl phthalate (DBP)
      under isothermal conditions at hydrostatic pressures up to 1.6 GPa. A comparison
      of the dielectric relaxation times with the viscosity revealed that no breakdown
      of the Einstein-Debye relation is induced by high compression. This absence of
      any decoupling is attributed to the weak intermolecular cooperativity of DBP and
      its negligible change with pressure. Because of the latter, the dielectric
      spectra conform to time-pressure superpositioning.

PMID- 12786084
TI  - Mechanical vertical manipulation of selected single atoms by soft nanoindentation
      using near contact atomic force microscopy.
AB  - A near contact atomic force microscope operated at low-temperature is used for
      vertical manipulation of selected single atoms from the Si(111)-(7 x 7) surface.
      The strong repulsive short-range chemical force interaction between the closest
      atoms of both tip apex and surface during a soft nanoindentation leads to the
      removal of a selected silicon atom from its equilibrium position at the surface
      without additional perturbation of the (7 x 7) unit cell. Deposition of a single
      atom on a created vacancy at the surface is achieved as well. These manipulation
      processes are purely mechanical, since neither bias voltage nor voltage pulse is
      applied between probe and sample. Differences in the mechanical response of the
      two nonequivalent adatoms of the Si(111)-(7 x 7) with the load applied is also
      detected.

PMID- 12786083
TI  - When scanning tunneling microscopy gets the wrong adsorption site: H on Rh(100).
AB  - At low tunneling resistance, scanning tunneling microscopy (STM) images of a
      Rh(100) surface with adsorbed hydrogen reproducibly show protrusions in all
      bridge sites of the surface, leading to a naive interpretation of all bridge
      sites being occupied with H atoms. Using quantitative low-energy electron
      diffraction and temperature programmed desorption we find a much lower H
      coverage, with most H atoms in fourfold hollow sites. Density functional theory
      calculations show that the STM result is due to the influence of the tip,
      attracting the mobile H atoms into bridge sites. This demonstrates that STM
      images of highly mobile adsorbates can be strongly misleading and underlines the
      importance of additional analysis techniques.

PMID- 12786085
TI  - Pattern selection in biaxially stressed solids.
AB  - We analyze the morphological instability of the surface of a solid which is
      subject to a biaxial stress. The stability calculation reveals a new favored
      pattern: a diamond morphology. This occurs if the stress is tensile in one
      direction and compressive in the orthogonal one and the ratio exceeds a certain
      value. A nonlinear analysis shows that the bifurcation is subcritical and hints
      to a nontrivial competition between tilted stripes and diamonds. This study opens
      a new line of inquiries in the field of stress-induced pattern selection.

PMID- 12786086
TI  - Nonequilibrium plasmons in a quantum wire single-electron transistor.
AB  - We analyze a single-electron transistor composed of two semi-infinite one
      dimensional quantum wires and a relatively short segment between them. We
      describe each wire section by a Luttinger model, and treat tunneling events in
      the sequential approximation when the system's dynamics can be described by a
      master equation. We show that the steady-state occupation probabilities in the
      strongly interacting regime depend only on the energies of the states and follow
      a universal form that depends on the source-drain voltage and the interaction
      strength.

PMID- 12786087
TI  - Diffusion thermopower of a two-dimensional hole gas in SiGe in a quantum Hall
      insulating state.
AB  - Both the temperature dependence of resistivity and thermopower of a two
      dimensional hole gas in SiGe show a reentrant metal-insulator transition at
      filling factor nu=1.5, but with strikingly different behavior of the two
      coefficients. As the temperature is decreased in the insulating state, the
      resistivity diverges exponentially while the thermopower decreases rapidly,
      suggesting that the insulating state is due to the presence of a mobility edge
      rather than a gap at the Fermi energy.

PMID- 12786089
TI  - Quantum-dot ground-state energies and spin polarizations: soft versus hard chaos.
AB  - We consider how the nature of the dynamics affects ground state properties of
      ballistic quantum dots. We find that "mesoscopic Stoner fluctuations" that arise
      from the residual screened Coulomb interaction are very sensitive to the degree
      of chaos. It leads to ground state energies and spin polarizations whose
      fluctuations strongly increase as a system becomes less chaotic. The crucial
      features are illustrated with a model that depends on a parameter that tunes the
      dynamics from nearly integrable to mostly chaotic.

PMID- 12786088
TI  - Carrier dynamics in conducting polymers: case of PF6 doped polypyrrole.
AB  - The carrier dynamics in PF6 doped polypyrrole has been probed by dielectric
      spectroscopy (from 10(-4) to 4 eV), down to 4.2 K. The phase-sensitive sub-THz
      data have assisted to resolve the discrepancies in Kramers-Kronig analysis in
      earlier studies. Even in metallic samples, just 1% of the carriers are
      delocalized, at 300 K; the fraction drops down considerably as a function of
      disorder, carrier density, and temperature. This subtle metallic feature and the
      anomalies in carrier dynamics are attributed to coherent and incoherent transport
      between short conjugated segments.

PMID- 12786090
TI  - Temperature-dependent third cumulant of tunneling noise.
AB  - Poisson statistics predicts that the shot noise in a tunnel junction has a
      temperature independent third cumulant e(2)I, determined solely by the mean
      current I. Experimental data, however, show a puzzling temperature dependence. We
      demonstrate theoretically that the third cumulant becomes strongly temperature
      dependent and may even change sign as a result of feedback from the
      electromagnetic environment. In the limit of a noninvasive (zero-impedance)
      measurement circuit in thermal equilibrium with the junction, we find that the
      third cumulant crosses over from e(2)I at low temperatures to -e(2)I at high
      temperatures.

PMID- 12786092
TI  - Electron-phonon scattering in quantum point contacts.
AB  - We study the negative correction to the quantized value 2e(2)/h of the
      conductance of a quantum point contact due to the backscattering of electrons by
      acoustic phonons. The correction shows activated temperature dependence and also
      gives rise to a zero-bias anomaly in conductance. Our results are in qualitative
      agreement with recent experiments studying the 0.7 feature in the conductance of
      quantum point contacts.

PMID- 12786091
TI  - Quantum partition noise of photon-created electron-hole pairs.
AB  - We show experimentally that even when no bias voltage is applied to a quantum
      conductor, the electronic quantum partition noise can be investigated with GHz
      radio frequency excitation. Using a quantum point contact configuration as the
      ballistic conductor we are able to make an accurate determination of the
      partition noise Fano factor resulting from the photon-assisted shot noise.
      Applying both voltage bias and rf irradiation we are able to make a definitive
      quantitative test of the scattering theory of photon-assisted shot noise.

PMID- 12786093
TI  - Fractional band filling in an atomic chain structure.
AB  - A new chain structure of Au is found on stepped Si(111) which exhibits a 1/4
      filled band and a pair of > or =1/2-filled bands with a combined filling of 4/3.
      Band dispersions and Fermi surfaces for Si(553)-Au are obtained by photoemission
      and compared to that of Si(557)-Au. The dimensionality of both systems is
      determined using a tight binding fit. The fractional band filling makes it
      possible to preserve metallicity in the presence of strong correlations.

PMID- 12786094
TI  - Electromagnetic realization of orders-of-magnitude tunneling enhancement in a
      double well system.
AB  - We report on tunneling enhancement in a periodically perturbed double well
      system. The double well system was realized by a structure of two optical
      waveguides. The transfer of light power from one waveguide to the another as
      induced by the periodic variations of the waveguide geometry was investigated.
      Our experimental measurements show that, in the presence of periodic
      perturbation, this transfer of light power can be enhanced by more than 500
      times. We use an analogy between electromagnetic wave optics and the quantum wave
      phenomena to provide an experimental support to the theoretical model of
      tunneling enhancement of a quantum particle, facilitated by its interaction with
      auxiliary quantum states.

PMID- 12786096
TI  - Mixed state of a dirty two-band superconductor: application to MgB2.
AB  - We investigate the vortex state in a two-band superconductor with strong
      intraband and weak interband electronic scattering rates. Coupled Usadel
      equations are solved numerically, and the distributions of the pair potentials
      and local densities of states are calculated for two bands at different values of
      magnetic fields. The existence of two distinct length scales corresponding to
      different bands is demonstrated. The results provide qualitative interpretation
      of recent scanning tunneling microscopy experiments on vortex structure imaging
      in MgB2.

PMID- 12786095
TI  - Evidence for nodal quasiparticles in the nonmagnetic superconductor YNi2B2C via
      field-angle-dependent heat capacity.
AB  - Field-angle dependent heat capacity of the nonmagnetic borocarbide superconductor
      YNi2B2C reveals a clear fourfold oscillation, the first observation of its kind.
      The observed angular variations were analyzed as a function of magnetic field
      angle, field-intensity, and temperature to provide its origin. The quantitative
      agreement between experiment and theory strongly suggests that we are directly
      observing nodal quasiparticles generated along <100> by the Doppler effect. The
      results demonstrate that field-angle heat capacity can be a powerful tool in
      probing the momentum-space gap structure in unconventional superconductors such
      as high T(c) cuprates, heavy-fermion superconductors, etc.

PMID- 12786097
TI  - Free energy fluctuations in Ising spin glasses.
AB  - The sample-to-sample fluctuations of the free energy in finite-dimensional Ising
      spin glasses are calculated, using the replica method, from higher order terms in
      the replica number n. It is shown that the Parisi symmetry breaking scheme does
      not give the correct answers for these higher order terms. A modified symmetry
      breaking scheme with the same stability is shown to resolve the problem.

PMID- 12786098
TI  - Spin diffusion in double-exchange manganites.
AB  - The theoretical study of spin diffusion in double-exchange magnets by means of
      dynamical mean-field theory is presented. We demonstrate that the spin-diffusion
      coefficient becomes independent of the Hund's coupling J(H) in the range of
      parameters J(H)S>>W>>T, W being the bandwidth, relevant to colossal
      magnetoresistive manganites in the metallic part of their phase diagram. Our
      study reveals a close correspondence as well as some counterintuitive differences
      between the results on Bethe and hypercubic lattices. Our results are in accord
      with neutron-scattering data and with previous theoretical work for high
      temperatures.

PMID- 12786099
TI  - Random potential effect near the bicritical region in perovskite manganites as
      revealed by comparison with the ordered perovskite analogs.
AB  - The orbital-charge-spin ordering phase diagram for half-doped perovskites
      Ln(1/2)Ba(1/2)MnO3 (Ln = rare earth) with ordered Ln/Ba cations has been
      investigated comparatively with that of the Ln/Ba solid-solution analogs. A large
      modification of the phase diagram is observed upon the A-site disordering near
      the original bicritical point between the charge-orbital ordering and
      ferromagnetic metallic phases. The random potential by quenched disorder inherent
      in the A-site solid solution is found to suppress the respective long-range
      orders and gives rise to the colossal magnetoresistive state.

PMID- 12786101
TI  - Quantum antiferromagnetism in quasicrystals.
AB  - The antiferromagnetic Heisenberg model is studied on a two-dimensional bipartite
      quasiperiodic lattice. Using the stochastic series expansion quantum Monte Carlo
      method, the distribution of local staggered magnetic moments is determined on
      finite square approximants with up to 1393 sites, and a nontrivial inhomogeneous
      ground state is found. A hierarchical structure in the values of the moments is
      observed which arises from the self-similarity of the quasiperiodic lattice. The
      computed spin structure factor shows antiferromagnetic modulations that can be
      measured in neutron scattering and nuclear magnetic resonance experiments. This
      generic model is a first step towards understanding magnetic quasicrystals such
      as the recently discovered Zn-Mg-Ho icosahedral structure.

PMID- 12786100
TI  - Structure and interaction of antiferromagnetic domain walls in hexagonal YMnO3.
AB  - The structure of antiferromagnetic (AFM) domain walls and their interaction with
      lattice strain are derived taking the multiple-order-parameter compound YMnO3 as
      a model example. Contrary to the conviction that AFM domain walls are
      energetically unfavorable, their interaction with lattice strain lowers the total
      energy of the system and leads to a piezomagnetic clamping of the electric and
      magnetic order parameters in good agreement with the available experimental data.

PMID- 12786102
TI  - Spectrum and correlation functions of a quasi-one-dimensional quantum Ising
      model.
AB  - For a model of weakly coupled quantum Ising chains we outline the phase diagram
      and establish that well below the transition line the system has a remarkably one
      dimensional spectrum. We study the dynamical magnetic susceptibility and find a
      very rich spectrum with several modes corresponding to a fundamental particle and
      its bound states. The approach is based on the Bethe ansatz and the random phase
      approximation applied to the interchain exchange.

PMID- 12786103
TI  - Electron-phonon scattering in metal clusters.
AB  - Electron-lattice energy exchanges are investigated in gold and silver
      nanoparticles with sizes ranging from 30 to 2.2 nm embedded in different
      environments. Femtosecond pump-probe experiments performed in the low
      perturbation regime demonstrate a strong increase of the intrinsic electron
      phonon interaction for nanoparticles smaller than 10 nm due to a confinement
      effect.

PMID- 12786104
TI  - Optical recognition of atomic steps on surfaces.
AB  - Visible and UV light spectra display striking differences in optical reflectivity
      for the two types of monatomic steps on copper (111) surfaces. Electronic
      structure calculations trace these differences to the specific contributions of
      p(axially) and p(radially) local densities of states, parallel and perpendicular
      to the steps, of the distinctly coordinated corner atoms. The local origin of the
      spectral reflectance anisotropy is further corroborated by experiments on Cu(111)
      surfaces with varying step densities. Site specificity of the electronic
      structure of atoms in low coordinated sites on Cu(111) vicinals is thus revealed
      by reflectance anisotropy spectroscopy which can thereby detect step atom
      densities down to 10(13) atoms/cm(2).

PMID- 12786105
TI  - Ascertaining the values of sigma x, sigma y, and sigma z of a polarization qubit.
AB  - In the 1987 spin-retrodiction puzzle of Vaidman, Aharonov, and Albert one is
      challenged to ascertain the values of sigma(x), sigma(y), and sigma(z) of a spin
      1/2 particle by utilizing entanglement. We report the experimental realization of
      a quantum-optical version in which the outcome of an intermediate polarization
      projection is inferred by exploiting single-photon two-qubit quantum gates. The
      experimental success probability is consistently above the 90.2% threshold of the
      optimal one-qubit strategy, with an average success probability of 95.6%.

PMID- 12786106
TI  - Thermal fluctuations and positional correlations in oriented lipid membranes.
AB  - We have determined the positional correlation functions in aligned stacks of
      fully hydrated phospholipid bilayers from the thermal diffuse scattering measured
      by nonspecular x-ray reflectivity. While fair agreement can be obtained between
      experiment and linear smectic theory at length scales above 120 A, significant
      deviations occur at small r, which are tentatively attributed to collective
      protrusion modes.

PMID- 12786107
TI  - Anomalous x-ray reflectivity characterization of ion distribution at biomimetic
      membranes.
AB  - Anomalous x-ray reflectivity measurements provides detailed information on ion
      binding to biomembrane surfaces. Using a monochromatic beam tuned to various x
      ray energies at the Argonne National Laboratory Advanced Photon Source and
      utilizing a newly commissioned x-ray liquid surfaces reflectometer, measurements
      at and away from ion absorption edges allow determination of the distribution of
      these ions as they accumulate near lipid membranes. As a model, the interaction
      of Ba2+ ions with DMPA- (1,2-dimyristoyl-sn-glycero-3-phosphatidic acid)
      monolayers at the aqueous surface is studied. We find an unexpectedly large
      concentration of barium at the interface, approximately 1.5 per DMPA-, forming a
      Stern layer of bound ions and a cloud of less densely bound ions near the lipid
      headgroups. This result can be understood only if one assumes that bound cations
      are partially speciated, e.g., as BaOH+.

PMID- 12786108
TI  - Zwicker tone illusion and noise reduction in the auditory system.
AB  - The Zwicker tone is an auditory aftereffect. For instance, after switching off a
      broadband noise with a spectral gap, one perceives it as a lingering pure tone
      with the pitch in the gap. It is a unique illusion in that it cannot be explained
      by known properties of the auditory periphery alone. Here we introduce a neuronal
      model explaining the Zwicker tone. We show that a neuronal noise-reduction
      mechanism in conjunction with dominantly unilateral inhibition explains the
      effect. A pure tone's "hole burning" in noisy surroundings is given as an
      illustration.

PMID- 12786109
TI  - Giant stress fluctuations at the jamming transition.
AB  - We study the stress response to a steady imposed shear rate in a concentrated
      suspension of colloidal particles. We show that, in a small range of
      concentrations and shear rates, stress exhibits giant fluctuations. The amplitude
      of these fluctuations obeys a power-law behavior, up to the apparition of a new
      branch of flow, leading to an excess of high amplitude fluctuations which exhibit
      a well-defined periodicity.

PMID- 12786110
TI  - A terahertz molecular switch.
AB  - We present time-dependent results describing the current through a molecular
      device, modeled as a complex with two active centers connected to leads under
      bias. We show that, at a properly adjusted external voltage, a passing terahertz
      electromagnetic pulse may cause a transition between states of finite and
      negligible current, suggesting that the system might be useful as a nanoscopic
      switch in the terahertz range. A phase diagram defining the bias region in which
      the transition takes place within a short time is given. As described, the
      physical processes involved are of an entirely different nature than those in
      ordinary photodetectors.

PMID- 12786111
TI  - Oscillatory Turing patterns in reaction-diffusion systems with two coupled
      layers.
AB  - A model reaction-diffusion system with two coupled layers yields oscillatory
      Turing patterns when oscillation occurs in one layer and the other supports
      stationary Turing structures. Patterns include "twinkling eyes," where
      oscillating Turing spots are arranged as a hexagonal lattice, and localized
      spiral or concentric waves within spot-like or stripe-like Turing structures. A
      new approach to generating the short-wave instability is proposed.

PMID- 12786112
TI  - Comment on "Phonon spectrum and dynamical stability of a dilute quantum
      degenerate Bose-Fermi mixture".

PMID- 12786113
TI  - Comment on "Investigating the phase diagram of finite extensive and nonextensive
      systems".

PMID- 12786115
TI  - Comment on "Aharonov-Bohm oscillations with spin: evidence for Berry's phase".

PMID- 12786117
TI  - Comment on "Conductivity of underdoped YBa2Cu3O7-delta: evidence for incoherent
      pair correlations in the pseudogap regime".

PMID- 12786119
TI  - Directed random walks on directed percolation clusters.
AB  - The characteristics of directed random walks on directed percolation clusters are
      numerically studied. For two-dimensional clusters grown at the critical
      probability p(c), it is shown that the distance d of the directed random walkers
      from their most probable end point is determined by a probability distribution
      p(d) approximately d(-(1+w/nu)), where the values of w and nu are close to the
      values of the known exponents: w approximately 0.50 and nu approximately 0.63.
      This probability distribution is independent of the cluster's length t up to d
      values comparable to the cluster's width approximately t(nu). The results are
      shown to be consistent with a tree description of the directed percolation
      clusters.

PMID- 12786120
TI  - Pattern formation in a rotating suspension of non-Brownian settling particles.
AB  - We report band formation and other pattern formation for a settling suspension of
      uniform non-Brownian particles in a completely filled horizontal rotating
      cylinder. The system shows a series of sharp pattern changes that are mapped out
      as a function of the rotation period and suspension viscosity. The experiment
      suggests that a large number of patterns and rich dynamics result from the
      interplay among the viscous drag, and gravitational and centrifugal forces.

PMID- 12786121
TI  - Asphaltene nanoparticle aggregation in mixtures of incompatible crude oils.
AB  - We study the structure and phase behavior of asphaltenes comprised of large
      polyaromatic molecules in blends of naturally occurring crude oils using small
      angle neutron scattering (SANS). When two compatible oils are blended together,
      the asphaltenes remain dispersed as colloidal nanoparticles; however, when two
      incompatible oils are blended together, these asphaltene nanoparticles can
      aggregate to form microscale structures. We show that SANS directly probes
      asphaltene aggregation in unmodified (i.e., nondeuterated) crude oil mixtures due
      to a significant neutron scattering length density difference between the
      hydrogen-poor asphaltenes and the surrounding oil. Moreover, the small length
      scales probed by SANS are ideally suited for studying asphaltene aggregation:
      SANS simultaneously provides the average size and concentration of nanoscale
      asphaltene particles and also the volume fraction of microscale asphaltene
      aggregates. These discoveries yield a practical means for directly assessing the
      compatibility of crude oils and for diagnosing refinery fouling problems
      resulting from blending incompatible oils.

PMID- 12786122
TI  - Self-diffusion in dilute colloidal suspensions with attractive potential
      interactions.
AB  - The colloidal short-time self-diffusivity D(s)(s)(phi) is significantly retarded
      relative to hard sphere suspensions for the case of interparticle potential
      interactions induced by a nonadsorbing polymer. A comparison of diffusing wave
      spectroscopy measurements with direct calculations of D(s)(s)(phi) demonstrates
      that depletion effects on structure explain the observed retardation. We show
      that coexistence boundaries place unexpectedly severe constraints on the amount
      of D(s)(s)(phi) retardation possible for stable suspensions. The measured
      retardation is demonstrated to be an indicator of suspension metastability.

PMID- 12786123
TI  - Effective pair potential between confined charged colloidal particles.
AB  - The pair correlation function g(r) between like-charged colloidal particles in
      quasi-two-dimensional geometries is measured by optical microscopy for a wide
      range of particle concentrations and various degrees of confinement. The
      effective pair potential u(r) is obtained by deconvoluting g(r) via Monte Carlo
      computer simulations. Our results confirm the existence of a long-range
      attractive component of u(r) and the appearance of an extra attractive term under
      stringent confinement.

PMID- 12786124
TI  - Magnetic-field-induced changes of the isotropic-nematic phase transition in side
      chain polymer liquid crystals.
AB  - The isotropic-nematic (I-N) phase transition of side-chain polymer liquid
      crystals is intrinsically a weak first-order transition with a biphasic region
      spread over a wide temperature interval. In the presence of high magnetic fields
      we find the I-N transition to become a strong first order. The I-N biphasic
      region shrinks its temperature window as larger magnetic fields are applied,
      until it completely disappears and the transition completes at a fixed
      temperature. We interpret this behavior as a consequence of the nonlinear
      coupling of the magnetic field to the system free energy, via the suppression of
      the order fluctuations in the nematic mesophase at the I-N transition crossing.

PMID- 12786125
TI  - Annihilation of nematic point defects: postcollision scenarios.
AB  - We perform a study of the annihilation of a nematic radial and hyperbolic point
      defects with the main focus on the confinement induced collision and
      postcollision scenarios. Brownian molecular dynamics on a semimicroscopic lattice
      is used. Initially a pair of defects, separated for 1.4-1.7 radii, is induced at
      the axis of the cylindrical capillary. In such a configuration defects start to
      approach slowly. In the early stage, their cores are negligibly influenced by the
      mutual interaction. When the distance becomes comparable to the nematic
      correlation length, the cores significantly deform. In the collision regime,
      defects gradually merge. We observe two qualitatively different scenarios in the
      postcollision regime, depending on the degree of (meta) stability of the
      initially imposed escaped structure with point defects.

PMID- 12786126
TI  - Structures and transitions in thin hybrid nematic films: a Monte Carlo study.
AB  - We confirm by Monte Carlo simulations of a Lebwohl-Lasher lattice spin model the
      existence of a biaxially ordered nonbent structure in a liquid-crystalline cell
      subject to opposing boundary conditions. We report on the observation of the
      bending transition from the biaxial to the bent-director structure when the
      temperature of the system is lowered. The structural transition is monitored both
      by the change of the order parameters and by heat capacity. We discuss the
      thickness dependence of the transition temperature by means of wetting-induced
      phenomena and elastic deformations. We propose the correspondence to the
      phenomenological description, which agrees well without any fitting parameters.

PMID- 12786129
TI  - Noise-induced failures of chaos stabilization: large fluctuations and their
      control.
AB  - Noise-induced failures in the stabilization of an unstable orbit in the one
      dimensional logistic map are considered as large fluctuations from a stable
      state. The properties of the large fluctuations are examined by determination and
      analysis of the optimal path and the optimal fluctuational force corresponding to
      the stabilization failure. The problem of controlling noise-induced large
      fluctuations is discussed, and methods of control have been developed.

PMID- 12786128
TI  - Granular fluid thermostated by a bath of elastic hard spheres.
AB  - The homogeneous steady state of a fluid of inelastic hard spheres immersed in a
      bath of elastic hard spheres kept at equilibrium is analyzed by means of the
      first Sonine approximation to the (spatially homogeneous) Enskog-Boltzmann
      equation. The temperature of the granular fluid relative to the bath temperature
      and the kurtosis of the granular distribution function are obtained as functions
      of the coefficient of restitution, the mass ratio, and a dimensionless parameter
      beta measuring the cooling rate relative to the friction constant. Comparison
      with recent results obtained from an iterative numerical solution of the Enskog
      Boltzmann equation [Biben et al., Physica A 310, 308 (2002)] shows an excellent
      agreement. Several limiting cases are also considered. In particular, when the
      granular particles are much heavier than the bath particles (but have a
      comparable size and number density), it is shown that the bath acts as a white
      noise external driving. In the general case, the Sonine approximation predicts
      the lack of a steady state if the control parameter beta is larger than a certain
      critical value beta(c) that depends on the coefficient of restitution and the
      mass ratio. However, this phenomenon appears outside the expected domain of
      applicability of the approximation.

PMID- 12786127
TI  - Preferential adsorption of hydrophobic-polar model proteins on patterned
      surfaces.
AB  - We study the adsorption of a single hydrophobic-polar (HP) model protein under
      the influence of a flat but specially designed surface. A folded HP model protein
      is brought to the surface with a designed pattern consisting of certain
      attractive and repulsive sites for the different monomers (amino acids). In
      contrast to the deformation of a random sequence that is continuous, deformation
      of any protein-like sequences is unlikely and an energy gap is associated with
      it. The surface with a certain wavelength of pattern attracts a certain type of
      folded structure preferentially and the free energy of the combined system is
      reduced. The model presented here represents a minimal theoretical model for
      protein recognition.

PMID- 12786131
TI  - Structural information in two-dimensional patterns: entropy convergence and
      excess entropy.
AB  - We develop information-theoretic measures of spatial structure and pattern in
      more than one dimension. As is well known, the entropy density of a two
      dimensional configuration can be efficiently and accurately estimated via a
      converging sequence of conditional entropies. We show that the manner in which
      these conditional entropies converge to their asymptotic value serves as a
      measure of global correlation and structure for spatial systems in any dimension.
      We compare and contrast entropy convergence with mutual-information and structure
      factor techniques for quantifying and detecting spatial structure.

PMID- 12786130
TI  - Kinetics of random aggregation-fragmentation processes with multiple components.
AB  - A computationally efficient algorithm is presented for exact simulation of the
      stochastic time evolution of spatially homogeneous aggregation-fragmentation
      processes featuring multiple components or conservation laws. The algorithm can
      predict the average size and composition distributions of aggregating particles
      as well as their fluctuations, regardless of the functional form (e.g.,
      composition dependence) of the aggregation or fragmentation kernels. Furthermore,
      it accurately predicts the complete time evolutions of all moments of the size
      and composition distributions, even for systems that exhibit gel transitions. We
      demonstrate the robustness and utility of the algorithm in case studies of linear
      and branched polymerization processes, the last of which is a two-component
      process. These simulation results provide the stochastic description of these
      processes and give new insights into their gel transitions, fluctuations, and
      long-time behavior when deterministic approaches to aggregation kinetics may not
      be reliable.

PMID- 12786132
TI  - Nonexistence of H theorems for the athermal lattice Boltzmann models with
      polynomial equilibria.
AB  - We prove that no H theorem exists for the athermal lattice Boltzmann equation
      with polynomial equilibria satisfying the conservation laws exactly and
      explicitly. The proof is demonstrated by using the seven-velocity model in a
      triangular lattice in two dimensions, and can be readily extended to other
      lattice Boltzmann models in two and three dimensions. Some issues pertinent to
      the numerical instabilities of the lattice Boltzmann method are discussed.

PMID- 12786133
TI  - Brownian particles in supramolecular polymer solutions.
AB  - The Brownian motion of colloidal particles embedded in solutions of hydrogen
      bonded supramolecular polymers has been studied using dynamic light scattering.
      At short times, the motion of the probe particles is diffusive with a diffusion
      coefficient equal to that in pure solvent. At intermediate time scales the
      particles are slowed down as a result of trapping in elastic cages formed by the
      polymer chains, while at longer times the motion is diffusive again, but with a
      much smaller diffusion coefficient. The influence of particle size and polymer
      concentration was investigated. The experimental data are compared to a
      theoretical expression for the mean-square displacement of an embedded particle
      in a viscoelastic medium, in which the solvent is explicitly taken into account.
      Differences between the friction and elastic forces experienced by the particle
      and the macroscopic viscosity and elasticity are explained by the inhomogeneity
      of the medium on the length scale of the particle size.

PMID- 12786134
TI  - Molecular dynamics simulation of compression-induced solid-to-solid phase
      transitions in colloidal monolayers.
AB  - The compression of two-dimensional colloidal monolayers, consisting of
      polystyrene particles trapped at an oil-water interface and interacting via
      dipole-dipole potentials, is investigated by the molecular dynamics technique. In
      particular, the pair correlation function and global orientational order
      parameter of the monolayers are calculated as a function of the particle
      coverage. The simulation results exhibit a sequence of hexagonal-to-rhombohedral
      to-hexagonal phase transitions of the monolayers under anisotropic compression.
      The influence of defects in the monolayers on the solid-to-solid phase
      transitions is also examined. The simulations show that the stability of the
      rhombohedral phase is relatively sensitive to lattice defects, while, under the
      same conditions, the hexagonal phase is very stable. Finally, the simulation
      results are compared with recent experimental observations, and the implications
      of the present computer simulations for diffusion mechanisms and protein folding
      studies are discussed briefly.

PMID- 12786135
TI  - Depinning of semiflexible polymers.
AB  - We present a theoretical analysis of a simple model of the depinning of an
      anchored semiflexible polymer from a fixed planar substrate in 1+1 dimensions. We
      consider a polymer with a discrete sequence of pinning sites along its contour.
      Using the scaling properties of the conformational distribution function in the
      stiff limit and applying the necklace model of phase transitions in quasi-one
      dimensional systems, we obtain a melting criterion in terms of the persistence
      length, the spacing between pinning sites, a microscopic effective length that
      characterizes a bond, and the bond energy. The limitations of this and other
      similar approaches are discussed. We also consider the general problem of thermal
      depinning in 1+d dimensions. In the case of force-induced unbinding, it is shown
      that the bending rigidity favors the unbinding through a "lever-arm effect."

PMID- 12786136
TI  - Exact solutions to nonlinear nonautonomous space-fractional diffusion equations
      with absorption.
AB  - We analyze a nonlinear fractional diffusion equation with absorption by employing
      fractional spatial derivatives and obtain some more exact classes of solutions.
      In particular, the diffusion equation employed here extends some known diffusion
      equations such as the porous medium equation and the thin film equation. We also
      discuss some implications by considering a diffusion coefficient D(x,t)=D(t)/x/(
      theta) (theta in R) and a drift force F=-k(1)(t)x+k(alpha)x/x/(alpha-1). In both
      situations, we relate our solutions to those obtained within the maximum entropy
      principle by using the Tsallis entropy.

PMID- 12786137
TI  - Moments of vicious walkers and Mobius graph expansions.
AB  - A system of Brownian motions in one dimension all started from the origin and
      conditioned never to collide with each other in a given finite time interval
      (0,T] is studied. The spatial distribution of such vicious walkers can be
      described by using the repulsive eigenvalue statistics of random Hermitian
      matrices and it was shown that the present vicious walker model exhibits a
      transition from the Gaussian unitary ensemble (GUE) statistics to the Gaussian
      orthogonal ensemble (GOE) statistics as the time t goes on from 0 to T. In the
      present paper, we characterize this GUE-to-GOE transition by presenting the
      graphical expansion formula for the moments of positions of vicious walkers. In
      the GUE limit t-->0, only the ribbon graphs contribute and the problem is reduced
      to the classification of orientable surfaces by genus. Following the time
      evolution of the vicious walkers, however, the graphs with twisted ribbons,
      called Mobius graphs, increase their contribution to our expansion formula, and
      we have to deal with the topology of nonorientable surfaces. Application of the
      recent exact result of dynamical correlation functions yields closed expressions
      for the coefficients in the Mobius expansion using the Stirling numbers of the
      first kind.

PMID- 12786138
TI  - Solution of the Percus-Yevick equation for square well spherocylinders.
AB  - The Percus-Yevick equation for square-well spherocylinders has been numerically
      solved for some selected orientations following a methodology proposed previously
      for different fluids of elongated molecules. The equation is solved for particles
      of aspect ratios ranging from L/sigma=0.3 up to L/sigma=5.0, attractive range
      lambda/sigma=1.5, and packing fractions within eta=0.1-0.3. The resulting pair
      correlation functions are checked against isothermal-isobaric Monte Carlo
      simulations and good agreement is found for the short-range structure, at
      intermolecular distances within one molecular diameter sigma to contact for each
      of the selected orientations. At larger distances, the integral equation tends to
      overestimate the pair correlations. The results confirm the prediction of
      reference-system average Mayer-function perturbation theory for short aspect
      ratios, reaching the Onsager limit for the greater aspect ratios. Some
      instabilities of the solution for the longest models and higher densities are
      tentatively discussed in terms of their possible relation to frustration
      phenomena found in some polymer and complex systems.

PMID- 12786139
TI  - Collective dynamics near fluid phase transitions.
AB  - By means of molecular dynamics simulations, we calculate the intermediate
      scattering function F(k(axially),t) where k(||) is the wave number and t is the
      time. We focus on thermodynamic states in the vicinity of a fluid phase
      transition in bulk and confined systems which we locate in parallel Monte Carlo
      simulations in the grand canonical ensemble. As one approaches the limit of
      stability of the fluid (i.e., its spinodal) from either low- or high-density
      branches of a subcritical isotherm, F(k(axially),t) becomes increasingly long
      range. The apparent lack of decorrelation in the metastable regime can be
      understood within the framework of a simple mean-field theory that links the long
      range nature of F(k(axially),t) to a divergence of the ratio of isostress and
      isochoric heat capacities gamma. Our results suggest that as one approaches the
      spinodal the dynamic structure factor S(k(axially),omega) (omega frequency),
      which is related to F(k(axially),t) through a Laplace transformation, should
      undergo a qualitative change from the usual triplet of Brillouin and Rayleigh
      lines to a singlet (delta-function-like peak) centered at omega=0 for states
      directly at the spinodal. This qualitative change in S(k(axially),omega) should
      be measurable in scattering experiments thereby promoting more detailed insight
      into the phase behavior and thermodynamic stability of confined and bulk fluids.

PMID- 12786140
TI  - Random packings of spheres and spherocylinders simulated by mechanical
      contraction.
AB  - We introduce a simulation technique for creating dense random packings of hard
      particles. The technique is particularly suited to handle particles of different
      shapes. Dense amorphous packings of spheres have been formed, which are
      consistent with the existing work on random sphere packings. Packings of
      spherocylinders have also been simulated out to the large aspect ratio of
      alpha=160.0. Our method packs randomly oriented spherocylinders to densities that
      reproduce experimental results on anisotropic powders and colloids very well.
      Interestingly, the highest packing density of phi=0.70 is achieved for very short
      spherocylinders rather than spheres. This suggests that slightly changing the
      shapes of the particles forming a hard sphere glass could cause it to melt.
      Comparisons between the equilibrium phase diagram for hard spherocylinders and
      the densest possible amorphous packings have interesting implications on the
      crystallization of spherocylinders as a function of aspect ratio.

PMID- 12786141
TI  - Two-dimensional packing in prolate granular materials.
AB  - We investigate the two-dimensional packing of extremely prolate (aspect ratio
      alpha=L/D>10) granular materials, comparing experiments with Monte Carlo
      simulations. The average packing fraction of particles with aspect ratio alpha=12
      is 0.68+/-0.03. We quantify the orientational correlation of particles and find a
      correlation length of two particle lengths. The functional form of the
      orientational correlation is the same in both experiments and simulations which
      three orders of magnitude in aspect ratio, all decaying over a distance of two
      particle lengths. It is possible to identify voids in the pile with sizes ranging
      over two orders of magnitude. The experimental void distribution function is a
      power law with exponent -beta=-2.43+/-0.08. Void distributions in simulated piles
      do not decay as a power law, but do show a broad tail. We extend the simulation
      to investigate the scaling at very large aspect ratios. A geometric argument
      predicts the pile number density to scale as alpha(-2). Simulations do indeed
      scale this way, but particle alignment complicates the picture, and the actual
      number densities are quite a bit larger than predicted.

PMID- 12786142
TI  - Development of correlations in the dynamics of wet granular avalanches.
AB  - A detailed characterization of avalanche dynamics of wet granular media in a
      rotating drum apparatus is presented. The results confirm the existence of the
      three wetness regimes observed previously: the granular, the correlated, and the
      viscoplastic regime. These regimes show qualitatively different dynamic behaviors
      that are reflected in all the investigated quantities. We discuss the effect of
      interstitial liquid on the characteristic angles of the material and on the
      avalanche size distribution. These data also reveal logarithmic aging and allow
      us to map out the phase diagram of the dynamic behavior as a function of liquid
      content and flow rate. Via quantitative measurements of the flow velocity and the
      granular flux during avalanches, we characterize avalanche types unique to wet
      media. We also explore the details of viscoplastic flow (observed at the highest
      liquid contents) in which there are lasting contacts during flow, leading to
      coherence across the entire sample. This coherence leads to a velocity
      independent flow depth at high rotation rates and robust pattern formation in the
      granular surface.

PMID- 12786143
TI  - Aeolian sand ripples around plants.
AB  - Plants in the desert may locally change the aeolian process, and hence the
      pattern of sand ripples traveling nearby. The effect of plants on ripples is
      investigated using a coupled map lattice model with nonuniform coupling
      coefficients.

PMID- 12786144
TI  - Effect of particle size and interparticle force on the fluidization behavior of
      gas-fluidized beds.
AB  - Gas-fluidized powders of fine particles display a fluidlike regime in which the
      bed does not have a yield strength, it expands uniformly as the gas velocity is
      increased and macroscopic bubbles are absent. In this paper we test the extension
      of this fluidlike regime as a function of particle size and interparticle
      attractive force. Our results show that for sufficiently large particles,
      bubbling initiates just after the solidlike fluidized regime as it is obtained
      experimentally by other workers. A scaling behavior of the solid-phase pressure
      in the fluidlike regime and a predictive criterion for the onset of macroscopic
      bubbling are analyzed in the light of these results.

PMID- 12786145
TI  - Avalanche dynamics, surface roughening, and self-organized criticality:
      Experiments on a three-dimensional pile of rice.
AB  - We present a two-dimensional system that exhibits features of self-organized
      criticality. The avalanches that occur on the surface of a pile of rice are found
      to exhibit finite size scaling in their probability distribution. The critical
      exponents are tau=1.21(2) for the avalanche size distribution and D=1.99(2) for
      the cutoff size. Furthermore, the geometry of the avalanches is studied, leading
      to a fractal dimension of the active sites of d(B)=1.58(2). Using a set of
      scaling relations, we can calculate the roughness exponent alpha=D-d(B)=0.41(3)
      and the dynamic exponent z=D(2-tau)=1.56(8). This result is compared with that
      obtained from a power-spectrum analysis of the surface roughness, which yields
      alpha=0.42(3) and z=1.5(1) in excellent agreement with those obtained from the
      scaling relations.

PMID- 12786146
TI  - Selective counterion condensation in ionic micellar solutions.
AB  - Small-angle neutron scattering experiments have been carried out on micellar
      solutions of cationic surfactants of cetyltrimethylammonium bromide (CTABr) and
      chloride (CTACl) in the presence of varying concentrations of salts KBr and KCl.
      In these systems, while the size of micelles strongly increases with the addition
      of KBr, the effect of addition of KCl in comparison is much less pronounced. It
      is found that in equimolar surfactant to salt micellar solutions of CTABr/KCl and
      CTACl/KBr, the micellar sizes are larger in CTACl/KBr than those in CTABr/KCl.
      The measurements have been done for different equimolar surfactant to salt
      concentrations and at different temperatures. We explain these results in terms
      of selective counterion condensation on the micelles. That is, while the
      condensation of Cl- counterions on the CTABr micelles in CTABr/KCl takes place
      around the condensed Br- counterions of CTABr, the Cl- counterions of CTACl in
      CTACl/KBr are replaced by Br- counterions of the salt. Similar results have also
      been obtained on micellar solutions of anionic surfactants of sodium dodecyl
      sulfate and lithium dodecyl sulfate in the presence of salts LiBr and NaBr,
      respectively.

PMID- 12786147
TI  - Nonlinear stress and fluctuation dynamics of sheared disordered wet foam.
AB  - A sheared wet foam, which stores elastic energy in bubble deformations, relaxes
      stress through bubble rearrangements. The intermittency of bubble rearrangements
      in the foam leads to effectively stochastic drops in stress that are followed by
      periods of elastic increase. We investigate global characteristics of highly
      disordered foams over three decades of strain rate and almost two decades of
      system size. We characterize the behavior using a range of measures: average
      stress, distribution of stress drops, rate of stress drops, and a normalized
      fluctuation intensity. There is essentially no dependence on system size. As a
      function of strain rate, there is a change in behavior around shear rates of 0.07
      s(-1).

PMID- 12786148
TI  - Magnetization of concentrated polydisperse ferrofluids: cluster expansion.
AB  - The equilibrium magnetization of concentrated ferrofluids described by a system
      of polydisperse dipolar hard spheres is calculated as a function of the internal
      magnetic field using the Born-Mayer or cluster expansion technique. This paper
      extends the results of Huke and Lucke [Phys. Rev. E 62, 6875 (2000)] obtained for
      monodisperse ferrofluids. The magnetization is given as a power series expansion
      in two parameters related to the volume fraction and the coupling strength of the
      dipolar interaction, respectively.

PMID- 12786149
TI  - Nonmonotonic variation with salt concentration of the second virial coefficient
      in protein solutions.
AB  - The osmotic virial coefficient B2 of globular protein solutions is calculated as
      a function of added salt concentration at fixed pH by computer simulations of the
      "primitive model." The salt and counterions as well as a discrete charge pattern
      on the protein surface are explicitly incorporated. For parameters roughly
      corresponding to lysozyme, we find that B2 first decreases with added salt
      concentration up to a threshold concentration, then increases to a maximum, and
      then decreases again upon further raising the ionic strength. Our studies
      demonstrate that the existence of a discrete charge pattern on the protein
      surface profoundly influences the effective interactions and that linear and
      nonlinear Poisson Boltzmann theories fail for large ionic strength. The observed
      nonmonotonicity of B2 is compared with experiments. Implications for protein
      crystallization are discussed.

PMID- 12786150
TI  - Electrorotation in graded colloidal suspensions.
AB  - Biological cells can be treated as composites of graded material inclusions. In
      addition to biomaterials, graded composites are important in more traditional
      materials science. In this paper, we investigate the electrorotation spectrum of
      a graded colloidal suspension in an attempt to discuss its dielectric properties.
      For that, we use the recently obtained differential effective dipole
      approximation and generalize it for nonspherical particles. We find that
      variations in the conductivity profile may make the characteristic frequency
      redshifted and have also an effect on the rotation peak. On the other hand,
      variations in the dielectric profile may enhance the rotation peak, but do not
      have any significant effect on the characteristic frequency. In the end, we apply
      our theory to fit experimental data obtained for yeast cells and find good
      agreement.

PMID- 12786152
TI  - Compressions of electrorheological fluids under different initial gap distances.
AB  - Compressions of electrorheological (ER) fluids have been carried out under
      different initial gap distances and different applied voltages. The nominal yield
      stresses of the compressed ER fluid under different conditions, according to the
      mechanics of compressing continuous fluids considering the yield stress of the
      plastic fluid, have been calculated. Curves of nominal yield stress under
      different applied voltages at an initial gap distance of 4 mm overlapped well and
      were shown to be proportional to the square of the external electric field and
      agree well with the traditional description. With the decrease of the initial gap
      distance, the difference between the nominal yield stress curves increased. The
      gap distance effect on the compression of ER fluids could not be explained by the
      traditional description based on the Bingham model and the continuous media
      theory. An explanation based on the mechanics of particle chain is proposed to
      describe the gap distance effect on the compression of ER fluids.

PMID- 12786151
TI  - Shear- and magnetic-field-induced ordering in magnetic nanoparticle dispersion
      from small-angle neutron scattering.
AB  - Small-angle neutron scattering experiments have been performed to investigate
      orientational ordering of a dispersion of rod-shaped ferromagnetic nanoparticles
      under the influence of shear flow and static magnetic field. In this experiment,
      the flow and flow gradient directions are perpendicular to the direction of the
      applied magnetic field. The scattering intensity is isotropic in zero-shear-rate
      or zero-applied-field conditions, indicating that the particles are randomly
      oriented. Anisotropic scattering is observed both in a shear flow and in a static
      magnetic field, showing that both flow and field induce orientational order in
      the dispersion. The anisotropy increases with the increase of field and with the
      increase of shear rate. Three states of order have been observed with the
      application of both shear flow and magnetic field. At low shear rates, the
      particles are aligned in the field direction. When increasing shear rate is
      applied, the particles revert to random orientations at a characteristic shear
      rate that depends on the strength of the applied magnetic field. Above the
      characteristic shear rate, the particles align along the flow direction. The
      experimental results agree qualitatively with the predictions of a mean field
      model.

PMID- 12786153
TI  - Continuous freezing in an infinite-range one-dimensional model.
AB  - The partition function of the classical one-dimensional hard rod fluid with a
      residual long range interaction can be evaluated exactly, with the aid of an
      auxiliary field, in the limit where the range of the potential goes to infinity.
      If the Fourier spectrum of the residual interaction lacks components at finite
      wave vector, the infinite range limit recovers the celebrated result of the Kac
      Uhlenbeck-Hemmer model of condensation. Otherwise, it predicts a continuous
      second-order freezing transition.

PMID- 12786154
TI  - Structure and stability of the interface between a strained crystal and a
      shearing liquid.
AB  - The results are presented from nonequilibrium molecular dynamics simulations of
      the stationary nonequilibrium interface between a shearing liquid and its
      strained crystal. The penetration of the velocity field into the crystal is shown
      to increase with an increasing shear stress along the coexistence line. Slip and
      creep compensate within the interfacial region to produce an effective flow
      boundary well described, macroscopically, by a standard stick boundary condition.
      The shear flow within the interface is found to involve intermittent stick-slip
      motion, with the slip accompanied by disordering. A theoretical treatment of the
      interfacial stability is proposed, based on the competing rates of
      crystallization and erosion, and is found to provide a reasonable representation
      of the simulated stress-temperature phase diagram.

PMID- 12786155
TI  - Diffusion and viscosity in a supercooled polydisperse system.
AB  - We have carried out extensive molecular dynamics simulations of a supercooled
      polydisperse Lennard-Jones liquid with large variations in temperature at a fixed
      pressure. The particles in the system are considered to be polydisperse in both
      size and mass. The temperature dependence of dynamical properties such as the
      viscosity (eta) and the self-diffusion coefficients (D(i)) of different size
      particles is studied. Both viscosity and diffusion coefficients show super
      Arrhenius temperature dependence and fit well to the well-known Vogel-Fulcher
      Tammann equation. Within the temperature range investigated, the value of
      Angell's fragility parameter (D approximately 1.4) classifies the present system
      as a very fragile liquid. The critical temperature for diffusion (T(D(i))(o))
      increases with the size of the particles. The critical temperature for viscosity
      (T(eta)(o)) is larger than that for diffusion, and sizable deviations appear for
      the smaller size particles, implying a decoupling of translational diffusion from
      viscosity in deeply supercooled liquids. Indeed, the diffusion shows markedly non
      Stokesian behavior at low temperatures where a highly nonlinear dependence on
      size is observed. An inspection of the trajectories of the particles shows that
      at low temperatures the motions of both the smallest and largest size particles
      are discontinuous (jump type). However, the crossover from continuous Brownian to
      large length hopping motion takes place at shorter time scales for the smaller
      size particles.

PMID- 12786156
TI  - Tagged particle motion in a dense liquid: feedback effects from the collective
      dynamics.
AB  - The nature of the tagged particle motion in the strongly correlated state of a
      dense liquid is studied with the self-consistent mode-coupling model. The tagged
      particle time correlation function psi(s)(q,t) is computed by taking into account
      the nonlinear feedback effects on its dynamics from the coupling with density
      fluctuations. We consider the two cases where (a) the short-time dynamics is
      diffusive resembling colloidal system and (b) the short-time dynamics is
      Newtonian as in an atomic system. The non-Gaussian parameter alpha(2)(t) is
      evaluated using the fourth- and second-order spatial moments of the van Hove self
      correlation function G(s)(r,t). We observe a two-peaked structure of alpha(2)(t)
      for both (a) and (b) types of dynamics. We also compare other characteristic
      aspects of tagged particle dynamics such as the mean square displacement, non
      Gaussian nature of G(s)(r,t), and fraction of mobile particles. A qualitative
      comparison is drawn between the theoretical results with the experimental and
      computer simulation results on colloids.

PMID- 12786157
TI  - Pore-level modeling of drainage: crossover from invasion percolation fingering to
      compact flow.
AB  - A pore-level model of drainage, which has been quantitatively validated, is used
      to study the effect of increased injection rate (i.e., increased capillary
      number) upon the flow, with matched-viscosity fluids. For small enough capillary
      number, the flows from the model correctly reproduce the flows from the invasion
      percolation with trapping (IPWT) model. As the capillary number is increased, the
      early-time flows mimic those of the IPWT-model, but then deviate towards compact
      flow at a characteristic time that decreases as the capillary number increases.
      That is, the larger the capillary number, the sooner the flow crosses over from
      IPWT flows towards compact (linear) flows.

PMID- 12786158
TI  - Time-resolved measurements of the dynamics of the photoinduced smectic-C* alpha
      smectic-A transition.
AB  - We present the study of the dynamics of the recently reported photoinduced
      smectic-C(*)(alpha)-smectic-A transition. High resolution time-resolved
      dielectric dispersion measurements carried out during the photoisomerization
      process demonstrate that the magnitude of the uv intensity mimics the role played
      by temperature in determining the behavior of the soft mode relaxation. We also
      show that the uv intensity dependence of the soft mode relaxation frequency f(R)
      in the photoinduced smectic-A phase can be described with a functional form
      similar to that derived for the temperature dependence of f(R) and compare the
      experimentally determined critical exponent with the theoretically predicted for
      the Ising and three-dimensional XY universality classes. Our study illustrates an
      interesting feature, namely, the magnitude of light intensity can be treated like
      a thermodynamic variable such as temperature and pressure to study phase
      transitions in general.

PMID- 12786159
TI  - Liquid crystal fibers of bent-core molecules.
AB  - Although the liquid-crystal research is well established in science, there are
      newly emerging exciting systems, that deserve extensive basic studies. One of
      these areas is the research of the bent-shaped molecules (so-called "banana
      liquid crystals"), which have delicate chirality and polarity properties. In this
      paper we show that these materials also have very unusual rheological features,
      such as the formation of stable fluid fibers and bridges. Under electric fields,
      these objects present striking mechanical effects, such as horizontal and
      transversal vibrations. Studies indicate that the research of banana-liquid
      crystal fibers may lead to new type of artificial muscle systems.

PMID- 12786160
TI  - Dynamic interaction between suspended particles and defects in a nematic liquid
      crystal.
AB  - Insertion of spherical particles into a uniform nematic liquid crystal gives rise
      to the formation of topological defects. In the present work, we investigate how
      a spherical particle accompanied by its topological defects interacts with
      neighboring disclination lines. We perform two- and three-dimensional dynamic
      simulations to analyze the effect of a particle on the annihilation process of
      two disclination lines. The dynamics of the liquid crystal is described by a time
      dependent evolution equation on the symmetric traceless order parameter that
      includes some of the salient features of liquid crystalline materials: excluded
      volume effects, or equivalently, short-range order elasticity and long-range
      order elasticity. At the surface of the particle, the liquid crystal is assumed
      to exhibit strong homeotropic anchoring. The particle is located between two
      disclination lines of topological charges +1/2 and -1/2. Two-dimensional
      simulations indicate that the topological defects bound to the particle mediate
      an interaction between the two disclination lines which increases the attraction
      between them. This result is confirmed by three-dimensional simulations that
      provide a complete description of the director field and of the order parameter
      around the particle. These simulations indicate that a spherical particle between
      two disclination lines can be surrounded by a Saturn ring, and suggest that the
      dynamic behavior of disclination lines could be used to report the structure of a
      defect around the particle.

PMID- 12786161
TI  - On-off intermittency in chaotic rotation induced in liquid crystals by
      competition between spin and orbital angular momentum of light.
AB  - We observed on-off intermittency in the chaotic rotation induced by a cw laser
      beam in a thin liquid crystal film where the spin and the orbital angular
      momentum of light compete in reorienting the sample. We found that the azimuthal
      angle phi(t) of the molecular director increased linearly in time on large time
      scales but, occasionally, it exhibited large fluctuations about its average value
      omega(0)t, so that its angular velocity phi;(t) undergoes an on-off intermittent
      motion. The intermittent signal omega(t)=phi;(t)-omega(0) obeyed the scaling laws
      of on-off intermittency, including the symmetry between laminar and burst phases.
      The chaotic rotations were observed only when the spin and the angular momentum
      of light were transferred simultaneously to the sample.

PMID- 12786162
TI  - Hydrodynamics of domain growth in nematic liquid crystals.
AB  - We study the growth of aligned domains in nematic liquid crystals. Results are
      obtained solving the Beris-Edwards equations of motion using the lattice
      Boltzmann approach. Spatial anisotropy in the domain growth is shown to be a
      consequence of the flow induced by the changing order parameter field (backflow).
      The generalization of the results to the growth of a cylindrical domain, which
      involves the dynamics of a defect ring, is discussed.

PMID- 12786163
TI  - Dynamic local-layer response of surface-stabilized ferroelectric liquid crystals
      to a high electric field by time-resolved x-ray microdiffraction.
AB  - Time-resolved synchrotron x-ray microdiffraction measurements have directly
      revealed the dynamic local-layer response to the high electric field in a surface
      stabilized ferroelectric liquid crystal. The irreversible layer transformation
      under the increasing electric field is found to consist of two stages; the
      initial vertical chevron structure transforms to the alternate vertical and
      horizontal chevrons and, with increasing field, the chevron angle decreases and
      the horizontal chevron structure develops. The time-resolved microdiffraction
      measurement has clarified the detailed reversible layer transformation between
      the mostly horizontal chevron at the high field and the so-called quasibookshelf
      at the low field during the ac field application. The transient layer response
      time is about 0.1-0.2 and 0.3-0.4 ms for falling and rising edges, respectively,
      and is slightly longer than the optical response time. The layer transformation
      is discussed in terms of electric torque and surface anchoring. The local-layer
      response in the antiferroelectric liquid crystal is also discussed for
      comparison.

PMID- 12786164
TI  - Second-harmonic generation from rubbed ferroelectric liquid crystal mesogenic
      monolayer surfaces.
AB  - We have designed self-assembled monolayers of molecules containing a
      ferroelectric liquid crystal mesogen attached to a glass surface through an
      alkane chain. After mechanical rubbing these layers induce a single domain in a
      cell containing a high-polarization achiral liquid crystal in the smectic-C
      phase. We have used optical second-harmonic generation to demonstrate that this
      behavior is explained by rubbing-induced in-plane anisotropy of the angular
      distribution function that describes the ensemble of mesogenic units. The surface
      order parameter is 0.094, a substantial fraction of what has been observed for
      rubbed polymeric alignment layers.

PMID- 12786165
TI  - Spontaneous periodic distortions in nematic liquid crystals: dependence on the
      tilt angle.
AB  - The possibility of spontaneous periodic distortions, depending on the tilt angle
      in a nematic liquid crystal sample, is investigated by means of a general
      formulation of the stability problem. It is shown that due to the presence of a
      surfacelike term in the free-energy density, the uniform pattern can be
      destabilized, giving rise to a periodic distortion of the director. Our analysis
      establishes, in general terms, the conditions for the formation of stable
      periodic structures in nematic samples. In particular, we determine the
      wavelengths for which the periodic distortion exists by investigating its
      dependence on the tilt angle, characterizing the uniform pattern, and on the
      saddle-splay elastic constant. The effect considered in our paper is a finite
      size effect, related to the slab geometry of the nematic sample under
      consideration.

PMID- 12786166
TI  - Comparison of the characteristics of the chiral analog of the de Vries type of
      smectic-A* phase.
AB  - In this paper we compare the results of three ferroelectric materials that
      exhibit unusual smectic-A (SmA) phases. These phases have been assigned to chiral
      analogs of the de Vries SmA phase. Several experimental techniques have been
      employed for this investigation. The possible molecular structures of de Vries
      SmA* phases are discussed.

PMID- 12786167
TI  - Biaxial melting of the nematic order under a strong electric field.
AB  - We study the action of a strong electric field on a nematic, topologically
      stabilized with director n perpendicular to E. Above a threshold field the
      nematic order on the cell midplane is "melted" and rapidly reconstructed with n
      axially E. In a Landau-de Gennes model, we show that the observed transient
      "melted" state is a biaxial nematic and not an isotropic liquid.

PMID- 12786168
TI  - Behavior of the nonlinear refractive indices and birefringence in the
      neighborhood of first- and second-order phase transitions in lyotropic liquid
      crystals.
AB  - We investigated the behavior of the nonlinear refractive indices (n(2)) and
      birefringence (Delta n(2)) in the vicinity of the nematic-to-isotropic (N-I) and
      nematic uniaxial-to-nematic biaxial (N-N) phase transitions in a lyotropic liquid
      crystal. The single-beam Z-scan technique is used to measure n(2) in different
      relative configurations of the electric field of the laser beam and the symmetry
      axes of the phases. In the N-I transition, the nonlinear optical birefringence
      shows a discontinuity at the transition temperature (T(c)), as observed in the
      linear birefringence. On the other hand, in the N-N transition, Delta n(2) was
      shown to be proportional to /T-T(c)/(-beta), with beta approximately 0.5, in both
      uniaxial and biaxial nematic domains. No discontinuity was observed on Delta n(2)
      in the N-N transition. The symmetric invariants of the order parameter were shown
      to be linear functions of the temperature in the uniaxial nematic domain, in good
      agreement with the mean-field prediction.

PMID- 12786169
TI  - Influence of density and temperature on the microscopic structure and the
      segmental relaxation of polybutadiene.
AB  - We investigate the influence of temperature and density on the local structure
      and the dynamics of polybutadiene by controlling both hydrostatic pressure and
      temperature in polarized neutron diffraction experiments on deuterated
      polybutadiene and in inelastic incoherent scattering experiments on protonated
      polybutadiene. We observe that the static structure factor S(Q) does not change
      along macroscopic isochores. This behavior is contrary to the relaxations
      observed on the nanosecond and picosecond time scales and viewed by the dynamic
      incoherent scattering law S(Q,omega), which differ strongly along the same
      thermodynamic path. We conclude that the static behavior, i.e., S(Q), is
      dominated by macroscopic density changes, similar to the vibrational excitations
      in the meV range. However, the relaxation dynamics is more sensitive to thermal
      energy changes. This is confirmed by the finding that lines of identical
      relaxation behavior (in time, shape, and Q dependence), isochrones on the 10(-9)
      sec time scale, clearly cross the constant density lines in the (P,T) plane.
      Concerning S(Q), we can reasonably relate the variation of the main-peak position
      to the average neighbor chain distance and deduce crude microscopic thermal
      expansion and compressibility coefficients. In the low-Q regime, the observed
      pressure and temperature variation of S(Q) exceeds the compressibility
      contribution and suggests the existence of additional scattering, which might
      originate from structural correlations arising at higher temperature and low
      pressure.

PMID- 12786170
TI  - Experimental evidence by neutron scattering of a crossover from Gaussian to non
      Gaussian behavior in the alpha relaxation of polyisoprene.
AB  - We report incoherent quasielastic neutron scattering experiments exploring the
      alpha-relaxation range in polyisoprene over an unprecedented range in momentum
      transfer Q. The data corroborate and validate earlier molecular dynamics
      simulations and reveal the existence of a crossover from Gaussian to non-Gaussian
      character of the main chain protons self-correlation function in the alpha
      relaxation regime. The real challenge of the experiment was to push the neutron
      techniques to cover a Q range as wide as possible. By combining two neutron spin
      echo spectrometers and a backscattering instrument, we have been able to study
      the dynamics in a Q range of 0.1 < or = Q < or = 4.7 A(-1). In the low-Q regime
      the shape of the relaxation function was found to be related to the dispersion of
      the relaxation times as predicted by the Gaussian assumption. At short distances
      or large Q, this relationship is strongly violated indicating a non-Gaussian
      regime. We have performed a detailed comparison between the experiments and
      simulations at different temperatures and found, apart from a temperature shift,
      complete agreement. Combining experiments and simulations led to a consistent
      interpretation in terms of a distribution of jumps underlying the diffusive
      motion of protons in the alpha process. This model leads to a time-dependent non
      Gaussianity parameter that agrees nearly quantitatively with the simulations and
      exhibits all features resolved so far from various simulations.

PMID- 12786171
TI  - Conformational properties of bottle-brush polymers.
AB  - General and renormalized perturbation theories are used to study the
      conformational properties of a bottle-brush molecule, composed of multiarmed
      polymer stars grafted regularly onto a flexible backbone. The end-to-end
      distances of the backbone and of an arm of the middle star are calculated within
      the first order of perturbation theory. For the high grafting densities of stars,
      the calculated expressions are generalized with the help of the scaling arguments
      to give the equivalent power laws. According to these laws, the molecule may
      adopt a sequence of three different conformations (star-rod-coil) as the length
      of the backbone grows.

PMID- 12786172
TI  - Conformation-dependent evolution of copolymer sequences.
AB  - A "toy model" of molecular evolution of sequences in copolymers is proposed and
      implemented using a molecular-dynamics-based algorithm. The model involves
      coupling of conformation-dependent and sequence-dependent properties. It is shown
      that this model allows the realization of two main possibilities: ascending and
      descending branches of evolution (in terms of information content of a sequence),
      depending on the interaction parameters shaping the conformation of a polymer
      globule. The problem of adequate description of information complexity of
      copolymer sequences is studied. It is shown that Shannon's entropy or
      compressibility of a sequence gives preference to random sequences and therefore
      cannot be applied for this purpose. On the other hand, the Jensen-Shannon
      divergence measure turns out to give the description of information complexity
      which corresponds to our intuitive expectations. In particular, this
      characteristic can adequately describe two branches of evolution mentioned above,
      exhibiting a singularity on the boundary of these regimes.

PMID- 12786173
TI  - Stochastic phase resetting of two coupled phase oscillators stimulated at
      different times.
AB  - A model of two coupled phase oscillators is presented, where the oscillators are
      subject to random forces and are stimulated at different times. Transient phase
      dynamics, synchronization, and desynchronization, which are stimulus locked
      (i.e., tightly time locked to a repetitively administered stimulus), are
      investigated. Complex coordinated responses, in terms of a noise-induced
      switching across trials between qualitatively different responses, may occur when
      the two oscillators are reset close to an unstable fixed point of their relative
      phases. This can be achieved with an appropriately chosen delay between the two
      stimuli. The switching of the responses shows up as a coordinated cross-trial
      (CT) response clustering of the oscillators, where the two oscillators produce
      two different pairs of responses. By varying noise amplitude and coupling
      strength we observe a stochastic resonance and a coupling-mediated resonance of
      the CT response clustering, respectively. The presented data analysis method
      makes it possible to detect such processes in numerical and experimental signals.
      Its time resolution is enormous, since it is only restricted by the time
      resolution of the preprocessing necessary for extracting the phases from
      experimental data. In contrast, standard data analysis tools applied across
      trials relative to stimulus onset, such as CT averaging (where an ensemble of
      poststimulus responses is simply averaged), CT standard deviation, and CT cross
      correlation, fail in detecting complex coordinated responses and lead to severe
      misinterpretations and artifacts. The consequences for the analysis of evoked
      responses in medicine and neuroscience are significant and are discussed in
      detail.

PMID- 12786174
TI  - Continuum of weakly coupled oscillatory McKean neurons.
AB  - The McKean model of a neuron possesses a one-dimensional fast voltagelike
      variable and a slow recovery variable. A recent geometric analysis of the
      singularly perturbed system has allowed an explicit construction of its phase
      response curve [S. Coombes, Physica D 160, 173 (2001)]. Here we use tools from
      coupled oscillator theory to study weakly coupled networks of McKean neurons.
      Using numerical techniques, we show that the McKean system has traveling wave
      phase-locked solutions consistent with that of a network of more biophysically
      detailed Hodgkin-Huxley neurons.

PMID- 12786175
TI  - Cell surface fluctuations studied with defocusing microscopy.
AB  - Phase objects can become visible by slightly defocusing an optical microscope, a
      technique seldom used as a useful tool. We revisited the theory of defocusing and
      apply it to our optical microscope with optics corrected at infinity. In our
      approximation, we obtain that the image contrast is proportional to the two
      dimensional (2D) Laplacian of the phase difference introduced by the phase
      object. If the index of refraction of the phase object is uniform the image
      obtained from defocusing microscopy is the image of curvature (Laplacian of the
      local thickness) of the phase object, while standard phase-contrast microscopy
      gives information about the thickness of the object. We made artificial phase
      objects and measured image contrasts with defocusing microscopy. Measured
      contrasts are in excellent agreement with our theoretical model. We use
      defocusing microscopy to study curvature fluctuations (ruffles) on the surface of
      macrophages (cell of the innate immune system), and try to correlate mechanical
      properties of macrophage surface and phagocytosis. We observe large coherent
      propagating structures: Their shape, speed, density are measured and curvature
      energy estimated. Inhomogeneities of cytoskeleton refractive index, curvature
      modulations due to thermal fluctuations and/or periodic changes in cytoskeleton
      membrane interactions cause random fluctuations in image contrast. From the
      temporal and spatial contrast correlation functions, we obtain the decay time and
      correlation length of such fluctuations that are related to their size and the
      viscoelastic properties of the cytoskeleton. In order to associate the dynamics
      of cytoskeleton with the process of phagocytosis, we use an optical tweezers to
      grab a zymosan particle and put it into contact with the macrophage. We then
      measure the time for a single phagocytosis event. We add the drug cytochalasin D
      that depolymerizes the cytoskeleton F-actin network: It inhibits the large
      propagating coherent fluctuations on the cell surface, increases the relaxation
      time of cytoskeleton fluctuations, and increases the phagocytosis time. Our
      results suggest that the methods developed in this work can be of utility to
      assess the importance of cytoskeleton motility in the dynamics of cellular
      processes such as phagocytosis exhibited by macrophages.

PMID- 12786176
TI  - Effects of quasiactive membrane on multiply periodic traveling waves in integrate
      and-fire systems.
AB  - We consider the dynamics of a one-dimensional continuum of synaptically
      interacting integrate-and-fire neurons with realistic forms of axodendritic
      interaction. The speed and stability of traveling waves are investigated as a
      function of discrete communication delays, distributed synaptic delays, and
      axodendritic delays arising from the spatially extended nature of the model
      neuron. In particular, dispersion curves for periodic traveling waves are
      constructed. Nonlinear ionic channels in the dendrite responsible for a so-called
      quasiactive bandpass response are shown to significantly influence the shape of
      dispersion curves. Moreover, a kinematic theory of spike train propagation
      suggests that period-doubling bifurcations of a singly periodic wave can occur in
      dendritic systems with a quasiactive membrane. The explicit construction of
      period-doubled solutions is used to confirm this prediction.

PMID- 12786177
TI  - Theory of high-force DNA stretching and overstretching.
AB  - Single-molecule experiments on single- and double-stranded DNA have sparked a
      renewed interest in the force versus extension of polymers. The extensible freely
      jointed chain (FJC) model is frequently invoked to explain the observed behavior
      of single-stranded DNA, but this model does not satisfactorily describe recent
      high-force stretching data. We instead propose a model (the discrete persistent
      chain) that borrows features from both the FJC and the wormlike chain, and show
      that it resembles the data more closely. We find that most of the high-force
      behavior previously attributed to stretch elasticity is really a feature of the
      corrected entropic elasticity; the true stretch compliance of single-stranded DNA
      is several times smaller than that found by previous authors. Next we elaborate
      our model to allow coexistence of two conformational states of DNA, each with its
      own stretch and bend elastic constants. Our model is computationally simple and
      gives an excellent fit through the entire overstretching transition of nicked,
      double-stranded DNA. The fit gives the first value for the bend stiffness of the
      overstretched state. In particular, we find the effective bend stiffness for DNA
      in this state to be about 12 nm k(B)T, a value quite different from either the B
      form or single-stranded DNA.

PMID- 12786178
TI  - Vaccination against rubella: analysis of the temporal evolution of the age
      dependent force of infection and the effects of different contact patterns.
AB  - In this paper, we analyze the temporal evolution of the age-dependent force of
      infection and incidence of rubella, after the introduction of a very specific
      vaccination program in a previously nonvaccinated population where rubella was in
      endemic steady state. We deduce an integral equation for the age-dependent force
      of infection, which depends on a number of parameters that can be estimated from
      the force of infection in a steady state prior to the vaccination program. We
      present the results of our simulations, which are compared with observed data. We
      also examine the influence of contact patterns among members of a community on
      the age-dependent intensity of transmission of rubella and on the results of
      vaccination strategies. As an example of the theory proposed, we calculate the
      effects of vaccination strategies for four communities from Caieiras (Brazil),
      Huixquilucan (Mexico), Finland, and the United Kingdom. The results for each
      community differ considerably according to the distinct intensity and pattern of
      transmission in the absence of vaccination. We conclude that this simple
      vaccination program is not very efficient (very slow) in the goal of eradicating
      the disease. This gives support to a mixed strategy, proposed by Massad et al.,
      accepted and implemented by the government of the State of Sao Paulo, Brazil.

PMID- 12786179
TI  - Lattice model for the kinetics of rupture of fluid bilayer membranes.
AB  - We have constructed a model for the kinetics of rupture of membranes under
      tension, applying physical principles relevant to lipid bilayers held together by
      hydrophobic interactions. The membrane is characterized by the bulk
      compressibility (for expansion) K, the thickness 2h(t) of the hydrophobic part of
      the bilayer, the hydrophobicity sigma, and a parameter gamma characterizing the
      tail rigidity of the lipids. The model is a lattice model which incorporates
      strain relaxation, and considers the nucleation of pores at constant area,
      constant temperature, and constant particle number. The particle number is
      conserved by allowing multiple occupancy of the sites. An equilibrium "phase
      diagram" is constructed as a function of temperature and strain with the total
      pore surface and distribution as the order parameters. A first-order rupture line
      is found with increasing tension, and a continuous increase in protopore
      concentration with rising temperature till instability. The model explains
      current results on saturated and unsaturated phosphatidylcholine lipid bilayers
      and thicker artificial bilayers made of diblock copolymers. Pore size
      distributions are presented for various values of area expansion and temperature,
      and the fractal dimension of the pore edge is evaluated.

PMID- 12786180
TI  - Role of bulk and of interface contacts in the behavior of lattice model dimeric
      proteins.
AB  - Some dimeric proteins first fold and then dimerize (three-state dimers) while
      others first dimerize and then fold (two-state dimers). Within the framework of a
      minimal lattice model, we can distinguish between sequences following one or the
      other mechanism on the basis of the distribution of the ground state energy
      between bulk and interface contacts. The topology of contacts is very different
      for the bulk than for the interface: while the bulk displays a rich network of
      interactions, the dimer interface is built up of a set of essentially independent
      contacts. Consequently, the two sets of interactions play very different roles
      both, in the folding and in the evolutionary history of the protein. Three-state
      dimers, where a large fraction of energy is concentrated in few contacts buried
      in the bulk, and where the relative contact energy of interface contacts is
      considerably smaller than that associated with bulk contacts, fold according to a
      hierarchical pathway controlled by local elementary structures, as also happens
      in the folding of single-domain monomeric proteins. On the other hand, two-state
      dimers display a relative contact energy of interface contacts, which is larger
      than the corresponding quantity associated with the bulk. In this case, the
      assembly of the interface stabilizes the system and leads the two chains to fold.
      The specific properties of three-state dimers acquired through evolution are
      expected to be more robust than those of two-state dimers; a fact that has
      consequences on proteins connected with viral diseases.

PMID- 12786181
TI  - Transverse fluctuations of single DNA molecules attached at both extremities to a
      surface.
AB  - We present a simple method to stretch DNA molecules close to a surface without
      any chemical modification of either the molecules or the surface. By adjusting
      the pH of the solution, only the extremities of DNA molecules are tethered to a
      glass coverslip made hydrophobic, while stretching is achieved using a
      hydrodynamic flow. These extended molecules provide a very favorable template for
      DNA-protein interaction studies by purely optical means. Pursuing these
      experiments requires first a full characterization of the thermally driven
      fluctuations of the tethered DNA molecules. For this purpose, these fluctuations
      were recorded by fluorescence microscopy and were analyzed in terms of normal
      modes. Our experimental results are well described by a model accounting for the
      nonlinear elastic behavior of the chain. Remarkably, the proximity of the
      molecules to a rigid surface does not alter the main features of their dynamics,
      and our results are in agreement with previous studies on extended DNA in viscous
      solutions.

PMID- 12786182
TI  - Diffusion coefficients of two-dimensional viral DNA walks.
AB  - DNA sequences are represented as two-dimensional walkers based on groups of
      mapping rules for the nucleotides in the DNA sequences. Digital sequences from
      irrational and random numbers in base 4 are generated and their diffusion
      properties are then compared with those of 21 nucleotide sequences of animal and
      plant viruses. By defining the diffusion coefficient as a function of the number
      of steps taken in a walk, we show that the coefficients for the viral DNA
      sequences generally have maximum values considerably larger than those for the
      random-number sequences of same lengths. Moreover, using the walker diagrams
      generated by different mapping groups, we can study the dominance of any of the
      nucleotide pairs (AG or CT), (AC or GT), or (AT or CG) in a DNA sequence. Other
      possible studies of this approach are mentioned.

PMID- 12786183
TI  - Wave-number spectrum of electrocorticographic signals.
AB  - A physiologically based continuum model of corticothalamic electrodynamics is
      generalized and used to derive the theoretical form of the electrocorticographic
      (ECoG) wave-number spectrum. A one-dimensional projection of the spectrum is
      derived, as is the azimuthally averaged two-dimensional spectrum for isotropic
      and anisotropic cortices. The predicted spectra are found to consist of a low-k
      plateau followed by three regions of power-law decrease, which result from
      filtering of the electrical activity through physical structures at different
      scales in the cortex. The magnitude of the maximum theoretical power-law exponent
      is larger for the two-dimensional (2D) spectrum than for its 1D counterpart. The
      predicted spectra agree well with experimental data obtained from 1D and 2D
      recording arrays on the cortical surface, enabling the structures in the brain
      that are important in determining spatial cortical dynamics to be identified. The
      cortical dispersion relation predicted by our model is also investigated,
      providing insight into the relationships between temporal and spatial brain
      dynamics.

PMID- 12786184
TI  - Self-organization and mechanical properties of active filament bundles.
AB  - A general framework for the description of active bundles of polar filaments is
      presented. The activity of the bundle results from mobile cross-links that induce
      relative displacements between the aligned filaments. Our generic description is
      based on momentum conservation within the bundle. By specifying the internal
      forces, a simple minimal model for the bundle dynamics can be derived, capturing
      a rich variety of dynamic behaviors. In particular, contracted states as well as
      solitary and oscillatory waves appear through dynamic instabilities. We present
      the full bifurcation diagram of this model and study the effects of a dynamic
      motor distribution on the bundle dynamics. Furthermore, we discuss the mechanical
      properties of the bundle in the presence of externally applied forces. Our
      description is motivated by dynamic phenomena in the cytoskeleton and could apply
      to in vitro experiments as well as to stress fibers and to self-organization
      phenomena during cell locomotion.

PMID- 12786185
TI  - Morphology transitions induced by chemotherapy in carcinomas in situ.
AB  - Recently, we have proposed a nutrient-limited model for the avascular growth of
      tumors including cell proliferation, motility, and death [S. C. Ferreira, Jr., M.
      L. Martins, and M. J. Vilela, Phys. Rev. E 65, 021907 (2002)], which
      qualitatively reproduces commonly observed morphologies for carcinomas in situ.
      In the present work, we analyze the effects of distinct chemotherapeutic
      strategies on the patterns, scaling, and growth laws obtained for the nutrient
      limited model. Two kinds of chemotherapeutic strategies were considered, namely,
      those that kill cancer cells and those that block cell mitosis but allow the cell
      to survive for some time. Depending on the chemotherapeutic schedule used, the
      tumors are completely eliminated, reach a stationary size, or grow following
      power laws. The model suggests that the scaling properties of the tumors are not
      affected by the mild cytotoxic treatments, although a reduction in growth rates
      and an increase in invasiveness are observed. For the strategies based on
      antimitotic drugs, a morphological transition in which compact tumors become more
      fractal under aggressive treatments was seen.

PMID- 12786186
TI  - Embedding a native state into a random heteropolymer model: the dynamic approach.
AB  - We study a random heteropolymer model with Langevin dynamics, in the
      supersymmetric formulation. Employing a procedure similar to one that has been
      used in static calculations, we construct an ensemble in which the affinity of
      the system for a native state is controlled by a "selection temperature" T0. In
      the limit of high T0, the model reduces to a random heteropolymer, while for T0-
      >0 the system is forced into the native state. Within the Gaussian variational
      approach that we employed previously for the random heteropolymer, we explore the
      phases of the system for high and low T0. For high T0, the system exhibits a
      (dynamical) spin-glass phase, like that found for the random heteropolymer, below
      a temperature T(g). For low T0, we find an ordered phase, characterized by a
      nonzero overlap with the native state, below a temperature T(n) proportional to
      1/T(0)>T(g). However, the random-globule phase remains locally stable below T(n),
      down to the dynamical glass transition at T(g). Thus, in this model, folding is
      rapid for temperatures between T(g) and T(n), but below T(g) the system can get
      trapped in conformations uncorrelated with the native state. At a lower
      temperature, the ordered phase can also undergo a dynamical glass transition,
      splitting into substates separated by large barriers.

PMID- 12786187
TI  - Firing-rate resonance in a generalized integrate-and-fire neuron with
      subthreshold resonance.
AB  - Neurons that exhibit a peak at finite frequency in their membrane potential
      response to oscillatory inputs are widespread in the nervous system. However, the
      influence of this subthreshold resonance on spiking properties has not yet been
      thoroughly analyzed. To this end, generalized integrate-and-fire models are
      introduced that reproduce at the linear level the subthreshold behavior of any
      given conductance-based model. A detailed analysis is presented of the simplest
      resonant model of this kind that has two variables: the membrane potential and a
      supplementary voltage-gated resonant variable. The firing-rate modulation created
      by a noisy weak oscillatory drive, mimicking an in vivo environment, is computed
      numerically and analytically when the dynamics of the resonant variable is slow
      compared to that of the membrane potential. The results show that the firing-rate
      modulation is shaped by the subthreshold resonance. For weak noise, the firing
      rate modulation has a minimum near the preferred subthreshold frequency. For
      higher noise, such as that prevailing in vivo, the firing-rate modulation peaks
      near the preferred subthreshold frequency.

PMID- 12786188
TI  - Nonlinear dynamical model of human gait.
AB  - We present a nonlinear dynamical model of the human gait control system in a
      variety of gait regimes. The stride-interval time series in normal human gait is
      characterized by slightly multifractal fluctuations. The fractal nature of the
      fluctuations becomes more pronounced under both an increase and decrease in the
      average gait. Moreover, the long-range memory in these fluctuations is lost when
      the gait is keyed on a metronome. Human locomotion is controlled by a network of
      neurons capable of producing a correlated syncopated output. The central nervous
      system is coupled to the motocontrol system, and together they control the
      locomotion of the gait cycle itself. The metronomic gait is simulated by a forced
      nonlinear oscillator with a periodic external force associated with the conscious
      act of walking in a particular way.

PMID- 12786189
TI  - Modified Michaelis law in a two-state ratchet model for a molecular motor as a
      function of diffusion constant.
AB  - We study transport properties and energetics of ratchets, which are driven by a
      chemical reaction between two states with different diffusion constants. We find
      that velocity curves show very sensitive dependence on the ratio of diffusion
      constants, whereas the rate of Adenosinetriphosphate (ATP) consumption curves
      depends smoothly on it. Modified Michaelis-Menten law shows us that identical
      values of Michaelis-Menten constant K(M) can be obtained independently from both
      curves. We obtain force-velocity curves for different values of a ratio of
      diffusion constants. We find that the Michaelis-Menten constant increases with
      the increasing external load for the "active site" model where the ATP assisted
      transition occurs at the localized region near the minimum of the ratchet
      potential, whereas it decreases with the increasing load for the "delocalized
      model."

PMID- 12786190
TI  - Relevance of structural segregation and chain compaction for the thermodynamics
      of folding of a hydrophobic protein model.
AB  - The relevance of inside-outside segregation and chain compaction for the
      thermodynamics of folding of a hydrophobic protein model is probed by complete
      enumeration of two-dimensional chains of up to 18 monomers in the square lattice.
      The exact computation of Z scores for uniquely designed sequences confirms that Z
      tends to decrease linearly with sigma square root of N, as previously suggested
      by theoretical analysis and Monte Carlo simulations, where sigma, the standard
      deviation of the number of contacts made by different monomers in the target
      structure, is a measure of structural segregation and N is the chain length. The
      probability that the target conformation is indeed the unique global energy
      minimum of the designed sequence is found to increase dramatically with sigma,
      approaching unity at maximal segregation. However, due to the huge number of
      conformations with sub-maximal values of sigma, which correspond to intermediate,
      only mildly discriminative, values of Z, in addition to significant oscillations
      of Z around its estimated value, the probability that a correctly designed
      sequence corresponds to a maximally segregated conformation is small. This
      behavior of Z also explains the observed relation between sigma and different
      measures of folding cooperativity of correctly designed sequences.

PMID- 12786191
TI  - DNA electrophoresis in dilute polymer solutions: a nonbinary mechanism.
AB  - The dynamical behavior of the neutral polymer (dextran, M(w)=2 x 10(6)) is
      investigated during DNA electrophoresis in a dilute solution. Using a
      fluorescence recovery after photobleaching setup, we measured the velocity of
      fluorescein-labeled dextran induced by the migration of the DNA. We found that
      each DNA molecule drags a large number of dextrans with it. We show that DNA
      dextran interactions are not only binary but long range and indirect. We conclude
      that the DNA-dextran complex creates a hydrodynamic field that entrains polymers
      far from the DNA during electrophoresis.

PMID- 12786192
TI  - Applicability of the Fisher equation to bacterial population dynamics.
AB  - The applicability of the Fisher equation, which combines diffusion with logistic
      nonlinearity, to population dynamics of bacterial colonies is studied with the
      help of explicit analytic solutions for the spatial distribution of a stationary
      bacterial population under a static mask. The mask protects bacteria from
      ultraviolet light. The solution, which is in terms of Jacobian elliptic
      functions, is used to provide a practical prescription to extract Fisher equation
      parameters from observations and to decide on the validity of the Fisher
      equation.

PMID- 12786193
TI  - Shil'nikov homoclinic chaos is intimately related to type-III intermittency in
      isolated rabbit arteries: role of nitric oxide.
AB  - We provide experimental evidence for the existence of Shil'nikov homoclinic chaos
      in the fluctuations in flow which can be observed in isolated perfused rabbit ear
      arteries, and establish a close association between homoclinicity and type-III
      Pomeau-Manneville intermittent behavior. The transition between the homoclinic
      scenario and type-III intermittency is clarified by a mathematical model of the
      arterial smooth muscle cell. Simulations of the effects of nitric oxide (NO) by
      the vascular endothelium on these patterns of behavior closely match experimental
      observations.

PMID- 12786194
TI  - Simulation of protonic fluctuations in hydrated protein powders.
AB  - Protons migrating on the surface of weakly hydrated protein powders provide a
      percolating mesoscopic system which exhibits charge fluctuations near room
      temperature. In this paper, we describe a simple numerical model where the
      statistical redistribution of protons on a space distribution of identical side
      chains lying on a spherical protein surface is varied by random ionization
      recombination process to investigate the noise power spectrum of the fluctuating
      dipole moment, the ergodicity of this system, and the occurrence of localized or
      extended proton distributions. The case of lysozyme is considered to this end.

PMID- 12786195
TI  - Estimate of the vibrational frequencies of spherical virus particles.
AB  - The possible normal modes of vibration of a nearly spherical virus particle are
      discussed. Two simple models for the particle are treated, a liquid drop model
      and an elastic sphere model. Some estimates for the lowest vibrational frequency
      are given for each model. It is concluded that this frequency is likely to be of
      the order of a few GHz for particles with a radius of the order of 50 nm.

PMID- 12786196
TI  - Approximate analytical solutions of the Bidomain equations for electrical
      stimulation of cardiac tissue with curving fibers.
AB  - The mechanism by which an applied electric field stimulates cardiac tissue far
      from the stimulating electrodes is not wholly understood. One possible mechanism
      relates the curving cardiac fibers to the induced membrane currents and
      transmembrane potentials. However, we lack a qualitative understanding of where
      these areas of polarization will occur when an electric field is applied to a
      sheet of cardiac tissue with curving fibers. In our study, we derive an
      analytical model for the transmembrane potential, dependent on the gradient of
      the fiber angle theta, for a two-dimensional passive sheet of cardiac tissue
      exhibiting various fiber geometries. Unequal anisotropy ratios are crucial for
      our results. We compare the results from our analytical solution to a numerical
      calculation using the full bidomain model. The results of our comparison are
      qualitatively consistent, albeit numerically different. We believe that our
      analytical approximation provides a reliable prediction of the polarization
      associated with an electric field applied to cardiac tissue with any fiber
      geometry and a qualitative understanding of the mechanisms behind the virtual
      electrode polarization.

PMID- 12786197
TI  - Quantum morphogenesis: a variation on Thom's catastrophe theory.
AB  - Noncommutative propositions are characteristic of both quantum and nonquantum
      (sociological, biological, and psychological) situations. In a Hilbert space
      model, states, understood as correlations between all the possible propositions,
      are represented by density matrices. If systems in question interact via feedback
      with environment, their dynamics is nonlinear. Nonlinear evolutions of density
      matrices lead to the phenomenon of morphogenesis that may occur in noncommutative
      systems. Several explicit exactly solvable models are presented, including "birth
      and death of an organism" and "development of complementary properties."

PMID- 12786198
TI  - Distances and classification of amino acids for different protein secondary
      structures.
AB  - Window profiles of amino acids in protein sequences are used to describe the
      amino acid environment. The relative entropy or Kullback-Leibler distance derived
      from these profiles is used as a measure of dissimilarity for comparison of amino
      acids and secondary structure conformations. Distance matrices of amino acid
      pairs at different conformations are obtained, which display a non-negligible
      dependence of amino acid similarity on conformations. Based on the conformation
      specific distances, a clustering analysis for amino acids is conducted.

PMID- 12786199
TI  - Periodic forcing of a model sensory neuron.
AB  - We study the effects of sinusoidally modulating the current injected into a model
      sensory neuron from the weakly electric fish Apteronotus leptorhynchus. This
      neuron's behavior is known to switch from quiescence to periodic firing to
      bursting as the injected current is increased. The bifurcation separating
      periodic from bursting behavior is a saddle-node bifurcation of periodic orbits,
      and it has been shown previously that there is "type-I burst excitability"
      associated with this bifurcation, similar to the usual excitability associated
      with the transition from quiescence to periodic firing. Here we show numerically
      that sinusoidal modulation of the dc current injected into the model neuron can
      switch it from periodic to burst firing, or vice versa, depending on the
      frequency of modulation and the distance to the burst excitability threshold.
      This is explained by mapping resonance tongues in parameter space. We also show
      that such a model neuron can undergo stochastic resonance near the transition
      from periodic to burst firing, as a result of the burst excitability, regardless
      of the location (soma or dendrite) of the signal and noise. The novelty is that
      the "output event" is now a burst rather than a single action potential, and the
      neuron returns to almost periodic firing between bursts, rather than to the
      vicinity of a fixed point. Since the neuron under study is a sensory neuron that
      must encode signals with varying temporal structure in the presence of
      considerable intrinsic noise, these aspects are of potential importance to
      electrosensory processing and also to other bursting neurons that have periodic
      input.

PMID- 12786200
TI  - Shear-induced solid-fluid transition in a wet granular medium.
AB  - We present a numerical study of a shear-induced solid-fluid transition in wet
      granular matter. The simulation is based on a simple model that considers both
      the cohesive forces induced by the adsorbed liquid amount and the repulsive
      forces due to the excluded volume interaction of the granules. Dissipation is
      assumed to be entirely due to the hysteretic character of the cohesive forces. In
      particular, we analyze the dynamics of the system close to the phase transition
      from solidlike behavior to a mobile ergodic state under the influence of an
      external force field F, when the latter exceeds a critical force F(c). Diffusion
      coefficients, dissipation, and kinetic order parameters can be expressed as
      characteristic scaling laws.

PMID- 12786201
TI  - Significance of the free volume for metastability, spinodals, and the glassy
      state: an exact calculation in polymers.
AB  - A lattice model of semiflexible linear chains (with equilibrium polydispersity)
      containing free volume is solved exactly on a Husimi cactus. A metastable liquid
      (ML) is discovered to exist only at low temperatures and is distinct (and may be
      disjoint) from the supercooled liquid (SCL) that exists only at high
      temperatures. The free volume plays a significant role in that the spinodals of
      the ML and SCL merge and then disappear as the free volume is reduced. The
      Kauzmann temperature T(K) occurs in the ML without any singularity. At
      T(MC)>T(K), the ML specific heat has a peak. For infinitely long polymers, the
      peak height diverges and the free volume vanishes at T(MC), resulting in a
      continuous liquid-liquid transition. Contrary to the conventional wisdom, both
      T(K) and T(MC) occur in the ML and not in the SCL.

PMID- 12786202
TI  - Shear-enhanced yield stress in electrorheological fluids.
AB  - We report the enhancement of yield stress in electrorheological (ER) fluids by a
      shear-annealing method, using creep-recovery (CR) cycles under an external
      electric field. The enhancement depends on the duration and the strength of the
      applied shear stress, as well as on the number of the CR cycles. The shear
      annealing method enables the particles in the ER fluid to form microstructures
      with an increased yield stress, manifest as better aligned and denser columns.
      For a sufficiently large number of CR cycles, with an optimal combination of
      stress duration and shear strength, a stable state can be obtained whereby shear
      deformation becomes elastic.

PMID- 12786203
TI  - Continuous demixing at liquid-vapor coexistence in a symmetrical binary fluid
      mixture.
AB  - We report a Monte Carlo finite-size scaling study of the demixing transition of a
      symmetrical Lennard-Jones binary fluid mixture. For equal concentration of
      species, and for a choice of the unlike-to-like interaction ratio delta=0.7, this
      transition is found to be continuous at liquid-vapor coexistence. The associated
      critical end point exhibits an Ising-like universality. These findings confirm
      those of earlier smaller scale simulation studies of the same model, but
      contradict the findings of recent integral equation and hierarchical reference
      theory investigations.

PMID- 12786204
TI  - Early stages of polymer interdiffusion.
AB  - We have examined the wavelength dependence of the diffusion coefficient in a
      multilayer deuterated polystyrene-hydrogenated polystyrene system. The
      measurements were performed using neutron reflectivity. The decay of the Bragg
      peak was also followed in great detail. The measured wavelength diffusion
      coefficient D(k) was also not found spatially dependent on the distance of the
      diffusional couples to the substrate. On the basis of our results, it was
      possible to reconstruct the broadening interface of polymer bilayer sample
      geometry which had characteristics of a diffuse tail and a sharp core.

PMID- 12786205
TI  - Simple model of the aging effect in heart interbeat time series.
AB  - In this work, we calculate the fractal dimension of heart interbeat time series
      of some healthy young and elderly individuals. As has been found by means of
      other methods (detrended fluctuation and spectral analyses), we also find that
      interbeat series of healthy young subjects can be characterized by only one
      scaling exponent and a crossover behavior in it is observed with aging. By means
      of a zoom over the hinges of the crossover region, interesting effects of aging
      are presented. Our results with real interbeat time series are reasonably
      reproduced by using a simple model based on combinations of noisy first-order
      autoregressive series.

PMID- 12786206
TI  - Wavelet analysis of epileptic spikes.
AB  - Interictal spikes and sharp waves in human EEG are characteristic signatures of
      epilepsy. These potentials originate as a result of synchronous pathological
      discharge of many neurons. The reliable detection of such potentials has been the
      long standing problem in EEG analysis, especially after long-term monitoring
      became common in investigation of epileptic patients. The traditional definition
      of a spike is based on its amplitude, duration, sharpness, and emergence from its
      background. However, spike detection systems built solely around this definition
      are not reliable due to the presence of numerous transients and artifacts. We use
      wavelet transform to analyze the properties of EEG manifestations of epilepsy. We
      demonstrate that the behavior of wavelet transform of epileptic spikes across
      scales can constitute the foundation of a relatively simple yet effective
      detection algorithm.

PMID- 12786207
TI  - Comments on nonlinear viscosity and Grad's moment method.
AB  - It is shown that the steady unidirectional flow with vanishing heat flux
      considered by B. C. Eu [Phys. Rev. E 65, 031202 (2002)], and earlier by Uribe and
      Garcia-Colin [Phys. Rev. E 60, 4052 (1999)], is inconsistent with the exact
      conservation laws of mass, momentum, and energy. The inconsistency does not lie
      in the assumed symmetry properties of the flow but in the stationarity
      assumption. The unsteady problem is considered and its solution from the
      Boltzmann equation for Maxwell molecules is given.

PMID- 12786210
TI  - Brownian motion with absolute negative mobility.
AB  - An example of Brownian motion with absolute negative mobility is given and
      analytically studied in a random walk and diffusion model.

PMID- 12786211
TI  - Direction of coupling from phases of interacting oscillators: an information
      theoretic approach.
AB  - A directionality index based on conditional mutual information is proposed for
      application to the instantaneous phases of weakly coupled oscillators. Its
      abilities to distinguish unidirectional from bidirectional coupling, as well as
      to reveal and quantify asymmetry in bidirectional coupling, are demonstrated
      using numerical examples of quasiperiodic, chaotic, and noisy oscillators, as
      well as real human cardiorespiratory data.

PMID- 12786212
TI  - Stability of classical chaotic motion under a system's perturbations.
AB  - We study in detail the time behavior of classical fidelity for chaotic systems.
      We show, in particular, that the asymptotic decay, depending on system dynamical
      properties, can be either exponential, with a rate determined by the gap in the
      discretized Perron-Frobenius operator, or algebraic, with the same power as for
      correlation functions decay. Therefore the decay of fidelity is strictly
      connected to correlations decay.

PMID- 12786213
TI  - Coherence properties near interfaces of random media.
AB  - The spatial coherence theory of optical fields radiated by statistically
      homogeneous, infinite, planar sources does not account for detailed surface
      characteristics. However, coherence properties change with the angular
      distribution of the intensity radiated from such a source, which, in turn,
      depends on the physical properties of the sample. We show that second-order
      correlations of the optical field measured at several wavelengths away from the
      surface of a highly inhomogeneous medium relate to the statistical
      characteristics of the interface.

PMID- 12786214
TI  - Use of sequential structure in simulation from high-dimensional systems.
AB  - Sampling from high-dimensional systems often suffers from the curse of
      dimensionality. In this paper, we explored the use of sequential structures in
      sampling from high-dimensional systems with an aim at eliminating the curse of
      dimensionality, and proposed an algorithm, so-called sequential parallel
      tempering as an extension of parallel tempering. The algorithm was tested with
      the witch's hat distribution and Ising model. Numerical results suggest that it
      is a promising tool for sampling from high-dimensional systems. The efficiency of
      the algorithm was argued theoretically based on the Rao-Blackwellization theorem.

PMID- 12786215
TI  - Structural transitions in scale-free networks.
AB  - Real growing networks such as the World Wide Web or personal connection based
      networks are characterized by a high degree of clustering, in addition to the
      small-world property and the absence of a characteristic scale. Appropriate
      modifications of the (Barabasi-Albert) preferential attachment network growth
      capture all these aspects. We present a scaling theory to describe the behavior
      of the generalized models and the mean-field rate equation for clustering. This
      is solved for a specific case with the result C(k) approximately 1/k for the
      clustering of a node of degree k. This mean-field exponent agrees with
      simulations, and reproduces the clustering of many real networks.

PMID- 12786216
TI  - Position-space renormalization-group approach for driven diffusive systems
      applied to the asymmetric exclusion model.
AB  - This paper introduces a position-space renormalization-group approach for
      nonequilibrium systems and applies the method to a driven stochastic one
      dimensional gas with open boundaries. The dynamics are characterized by three
      parameters: the probability alpha that a particle will flow into the chain to the
      leftmost site, the probability beta that a particle will flow out from the
      rightmost site, and the probability p that a particle will jump to the right if
      the site to the right is empty. The renormalization-group procedure is conducted
      within the space of these transition probabilities, which are relevant to the
      system's dynamics. The method yields a critical point at alpha(c)=beta(c)=1/2, in
      agreement with the exact values, and the critical exponent nu=2.71, as compared
      with the exact value nu=2.00.

PMID- 12786217
TI  - Growing network with local rules: preferential attachment, clustering hierarchy,
      and degree correlations.
AB  - The linear preferential attachment hypothesis has been shown to be quite
      successful in explaining the existence of networks with power-law degree
      distributions. It is then quite important to determine if this mechanism is the
      consequence of a general principle based on local rules. In this work it is
      claimed that an effective linear preferential attachment is the natural outcome
      of growing network models based on local rules. It is also shown that the local
      models offer an explanation for other properties like the clustering hierarchy
      and degree correlations recently observed in complex networks. These conclusions
      are based on both analytical and numerical results for different local rules,
      including some models already proposed in the literature.

PMID- 12786218
TI  - Phase-separating binary fluids under oscillatory shear.
AB  - We apply the lattice Boltzmann methods to study the segregation of binary fluid
      mixtures under oscillatory shear flow in two dimensions. The algorithm allows to
      simulate systems whose dynamics is described by the Navier-Stokes and the
      convection-diffusion equations. The interplay between several time scales
      produces a rich and complex phenomenology. We investigate the effects of
      different oscillation frequencies and viscosities on the morphology of the phase
      separating domains. We find that at high frequencies the evolution is almost
      isotropic with growth exponents 2/3 and 1/3 in the inertial (low viscosity) and
      diffusive (high viscosity) regimes, respectively. When the period of the applied
      shear flow becomes of the same order of the relaxation time T(R) of the shear
      velocity profile, anisotropic effects are clearly observable. In correspondence
      with nonlinear patterns for the velocity profiles, we find configurations where
      lamellar order close to the walls coexists with isotropic domains in the middle
      of the system. For particular values of frequency and viscosity it can also
      happen that the convective effects induced by the oscillations cause an
      interruption or a slowing of the segregation process, as found in some
      experiments. Finally, at very low frequencies, the morphology of domains is
      characterized by lamellar order everywhere in the system resembling what happens
      in the case with steady shear.

PMID- 12786219
TI  - Transport on percolation clusters with power-law distributed bond strengths.
AB  - The simplest transport problem, namely finding the maximum flow of current, or
      maxflow, is investigated on critical percolation clusters in two and three
      dimensions, using a combination of extremal statistics arguments and exact
      numerical computations, for power-law distributed bond strengths of the type
      P(sigma) approximately sigma(-alpha). Assuming that only cutting bonds determine
      the flow, the maxflow critical exponent v is found to be v(alpha)=(d-1)nu+1/(1
      alpha). This prediction is confirmed with excellent accuracy using large-scale
      numerical simulation in two and three dimensions. However, in the region of
      anomalous bond capacity distributions (0< or =alpha< or =1) we demonstrate that,
      due to cluster-structure fluctuations, it is not the cutting bonds but the blobs
      that set the transport properties of the backbone. This "blob dominance" avoids a
      crossover to a regime where structural details, the distribution of the number of
      red or cutting bonds, would set the scaling. The restored scaling exponents,
      however, still follow the simplistic red bond estimate. This is argued to be due
      to the existence of a hierarchy of so-called minimum cut configurations, for
      which cutting bonds form the lowest level, and whose transport properties scale
      all in the same way. We point out the relevance of our findings to other scalar
      transport problems (i.e., conductivity).

PMID- 12786220
TI  - Effect of inert species in gas phase on oscillatory dynamics of oxidation system
      of CO on Pt(100).
AB  - We present a Monte Carlo simulation for the global oscillation of the CO
      catalytic oxidation system in the presence of inert species in gas phase, which
      can adsorb and desorb on the catalytic surface but cannot react with other
      species. It is found that the impurity has a dramatic effect on the oscillatory
      dynamics, although it does not involve in the reaction of CO oxidation. The
      simulation results show that with an increase in the fraction of impurity in gas
      phase, the periodic oscillation may change into an irregular oscillation and even
      can be inhibited completely. However, as the desorption rate of the impurity is
      increased, the regular oscillation will be recovered again.

PMID- 12786221
TI  - Splitting the voter Potts model critical point.
AB  - Recently some two-dimensional models with double symmetric absorbing states were
      shown to share the same critical behavior that was called the voter universality
      class. We show that, for an absorbing-states Potts model with finite but further
      than nearest-neighbor range of interactions, the critical point is split into two
      critical points: one of the Ising type and the other of the directed percolation
      universality class. Similar splitting takes place in the three-dimensional
      nearest-neighbor model.

PMID- 12786222
TI  - Distribution and density of the partition function zeros for the diamond
      decorated Ising model.
AB  - Exact renormalization map of temperature between two successive decorated
      lattices is given, and the distribution of the partition function zeros in the
      complex temperature plane is obtained for any decoration level. The rule
      governing the variation of the distribution pattern as the decoration level
      changes is given. The densities of the zeros for the first two decoration levels
      are calculated explicitly, and the qualitative features about the densities of
      higher decoration levels are given by conjecture. The Julia set associated with
      the renormalization map is contained in the distribution of the zeros in the
      limit of infinite decoration level, and the formation of the Julia set in the
      course of increasing the decoration level is given in terms of the variations of
      the zero density.

PMID- 12786223
TI  - Breaking of general rotational symmetries by multidimensional classical ratchets.
AB  - We demonstrate that a particle driven by a set of spatially uncorrelated,
      independent colored noise forces in a bounded, multidimensional potential
      exhibits rotations that are independent of the initial conditions. We calculate
      the particle currents in terms of the noise statistics and the potential
      asymmetries by deriving an n-dimensional Fokker-Planck equation in the small
      correlation time limit. We analyze a variety of flow patterns for various
      potential structures, generating various combinations of laminar and rotational
      flows.

PMID- 12786224
TI  - Time-reversed dielectric-breakdown model for erosion phenomena.
AB  - A time-reversed dielectric-breakdown model in which the annihilating probability
      of a particle on the surface site (x,h) depends on Laplacian field phi(x,h,t) as
      P(x,h,t)=| inverted Delta phi(x,h,t)|(kappa)/ Sigma(x,h)| inverted Delta
      phi(x,h,t)|(kappa) is suggested. This model is shown to be a theoretical model
      that covers a variety of eroding surfaces from the linear phenomena with dynamic
      exponent z=1 to those showing nonlinear behavior. phi(x,t) is defined to satisfy
      the Laplace equation inverted Delta (2)phi=0 with the boundary condition phi=0 on
      the material and phi=1 far from the material. The model with 0.5 < or = kappa <
      or = 2 is found to follow the linear growth equation with z=1 as the diffusion
      limited erosion, which is also a time-reversed version of diffusion-limited
      deposition. For small kappa, the dynamical scaling property of the eroding
      surface belongs to the Kardar-Parisi-Zhang universal class as the time-reversed
      Eden model. The model with kappa >2.5 does not show any surface roughening
      behavior.

PMID- 12786225
TI  - Stochastic resonance in vertical-cavity surface-emitting lasers based on a
      multiple time-scale analysis.
AB  - We provide analytical evidence of stochastic resonance in polarization switching
      vertical-cavity surface-emitting lasers (VCSELs). We describe the VCSEL by a two
      mode stochastic rate equation model and apply a multiple time-scale analysis. We
      were able to reduce the dynamical description to a single stochastic differential
      equation, which is the starting point of the analytical study of stochastic
      resonance. We confront our results with numerical simulations on the original
      rate equations, validating the use of a multiple time-scale analysis on
      stochastic equations as an analytical tool.

PMID- 12786226
TI  - Critical properties of loop percolation models with optimization constraints.
AB  - We study loop percolation models in two and in three space dimensions, in which
      configurations of occupied bonds are forced to form a closed loop. We show that
      the uncorrelated occupation of elementary plaquettes of the square and the simple
      cubic lattice by elementary loops leads to a percolation transition that is in
      the same universality class as the conventional percolation. In contrast to this,
      an optimization constraint for the loop configurations, which then have to
      minimize a particular generic energy function, leads to a percolation transition
      that constitutes a universality class for which we report the critical exponents.
      Implication for the physics of solid-on-solid and vortex glass models are
      discussed.

PMID- 12786227
TI  - Phase transition classes in triplet and quadruplet reaction-diffusion models.
AB  - Phase transitions of reaction-diffusion systems with site occupation restriction
      and with particle creation that requires n=3,4 parents, whereas explicit
      diffusion of single particles (A) is present are investigated in low dimensions
      by the mean-field approximation and simulations. The mean-field approximation of
      general nA-->(n+k)A, mA-->(m-l)A type of lattice models is solved and a different
      kind of critical behavior is pointed out. In d=2 dimensions, the 3A-->4A, 3A-->2A
      model exhibits a continuous mean-field type of phase transition, that implies
      d(c)<2 upper critical dimension. For this model in d=1 extensive simulations
      support a mean-field type of phase transition with logarithmic corrections unlike
      the recent study of Park et al. [Phys. Rev E 66, 025101 (2002)]. On the other
      hand, the 4A-->5A, 4A-->3A quadruplet model exhibits a mean-field type of phase
      transition with logarithmic corrections in d=2, while quadruplet models in one
      dimensional show robust, nontrivial transitions suggesting d(c)=2. Furthermore, I
      show that a parity conserving model 3A-->5A, 2A--> zero in d=1 has a continuous
      phase transition with different kinds of exponents. These results are in
      contradiction with the recently suggested implications of a phenomenological,
      multiplicative noise Langevin equation approach and with the simulations on
      suppressed bosonic systems by Kockelkoren and Chate [Phys. Rev. Lett. 90, 125701
      (2003)].

PMID- 12786228
TI  - Minimal renormalization without epsilon expansion: four-loop free energy in three
      dimensions for general n above and below Tc.
AB  - We present an analytic four-loop calculation of the free energy in three
      dimensions within the O(n) symmetric phi(4) theory at infinite cutoff for general
      n above and below T(c). It is shown that Goldstone singularities arising at
      intermediate stages of the calculation cancel among themselves. The correlation
      length above T(c) and an appropriately defined pseudocorrelation length below
      T(c) are calculated analytically up to four-loop order for general n. The method
      of minimal renormalization at fixed dimension d=3 is used to determine the
      analytic expressions for the four-loop series of the amplitude functions of the
      free energy, correlation length, and specific heat above and below T(c) in terms
      of the renormalized coupling. These expressions provide the basis for future
      accurate Borel resummations of universal amplitude ratios characterizing the
      asymptotic critical behavior and of crossover functions describing the
      nonasymptotic critical behavior. A brief application is given by a variational
      calculation of the universal specific-heat amplitude ratios A+/A- and P=alpha(
      1)(1-A+/A-) and of the universal quantity R+(xi)=xi+0(A+)(1/d) for general n.

PMID- 12786229
TI  - Does the transverse electric zero mode contribute to the Casimir effect for a
      metal?
AB  - The finite-temperature Casimir free energy, entropy, and internal energy are
      considered anew for a conventional parallel-plate configuration, in the light of
      current discussions in the literature. In the case of an "ideal" metal,
      characterized by a refractive index equal to infinity for all frequencies, we
      recover, via a somewhat unconventional method, conventional results for the
      temperature dependence, meaning that the zero-frequency transverse electric mode
      contributes the same as the transverse magnetic mode. For a real metal, however,
      approximately obeying the Drude dispersive model at low frequencies, we find that
      the zero-frequency transverse electric mode does not contribute at all. This
      would appear to lead to an observable temperature dependence and a violation of
      the third law of thermodynamics. It had been suggested that the source of the
      difficulty was the behavior of the reflection coefficient for perpendicular
      polarization but we show that this is not the case. By introducing a simplified
      model for the Casimir interaction, consisting of two harmonic oscillators
      interacting via a third one, we illustrate the behavior of the transverse
      electric field. Numerical results are presented based on the refractive index for
      gold. A linear temperature correction to the Casimir force between parallel
      plates is indeed found which should be observable in room-temperature
      experiments, but this does not entail any thermodynamic inconsistency.

PMID- 12786230
TI  - Star-unitary transformations: from dynamics to irreversibility and stochastic
      behavior.
AB  - We consider a simple model of a classical harmonic oscillator coupled to a field.
      In standard approaches, Langevin-type equations for bare particles are derived
      from Hamiltonian dynamics. These equations contain memory terms and are time
      reversal invariant. In contrast, the phenomenological Langevin equations have no
      memory terms (they are Markovian equations) and give a time-evolution split in
      two branches (semigroups), each of which breaks time symmetry. A standard
      approach to bridge dynamics with phenomenology is to consider the Markovian
      approximation of the former. In this paper, we present a formulation in terms of
      dressed particles, which gives exact Markovian equations. We formulate dressed
      particles for Poincare nonintegrable systems, through an invertible
      transformation operator Lambda introduced by Prigogine and co-workers. Lambda is
      obtained by an extension of the canonical (unitary) transformation operator U
      that eliminates interactions for integrable systems. Our extension is based on
      the removal of divergences due to Poincare resonances, which breaks time
      symmetry. The unitarity of U is extended to "star unitarity" for Lambda. We show
      that Lambda-transformed variables have the same time evolution as stochastic
      variables obeying Langevin equations, and that Lambda-transformed distribution
      functions satisfy exact Fokker-Planck equations. The effects of Gaussian white
      noise are obtained by the nondistributive property of Lambda with respect to
      products of dynamical variables.

PMID- 12786231
TI  - Stability analysis of mean-field-type nonlinear Fokker-Planck equations
      associated with a generalized entropy and its application to the self-gravitating
      system.
AB  - Multidimensional nonlinear Fokker-Planck equations of mean-field type are
      proposed within the framework of generalized thermostatistics to develop a
      general formulation of stability analysis of their solutions. Two types of
      eigenvalue equations are studied. The nonlinear Fokker-Planck equations are shown
      to exhibit an H theorem with a Liapunov functional that takes the form of a free
      energy involving generalized entropies of Tsallis. The second-order variation of
      the Liapunov functional is computed to conduct local stability analysis and the
      associated eigenvalue equation is derived for an arbitrary form of mean-field
      coupling potential. Assuming quasiequilibrium for the velocity distribution, the
      reduced eigenvalue equation with space coordinates alone is also obtained. The
      alternative type of eigenvalue equation based on the linearization of the
      nonlinear Fokker-Planck equations is presented. Taking the mean-field coupling
      potential to be the gravitational one, the nonlinear Fokker-Planck equation in
      terms of three-dimensional velocity and space coordinates together with the
      framework of stability analysis is shown to be applicable to a mean-field model
      of self-gravitating system. By solving the eigenvalue equation for the
      eigenfunction with 0 eigenvalue, the occurrence of stability change of the
      equilibrium probability density with spherical symmetry is discussed.

PMID- 12786232
TI  - Size of quantum networks.
AB  - The metric structure of bosonic scale-free networks and fermionic Cayley-tree
      networks is analyzed, focusing on the directed distance of nodes from the origin.
      The topology of the networks strongly depends on the dynamical parameter T,
      called the temperature. At T= infinity we show analytically that the two networks
      have a similar behavior: the distance of a generic node from the origin of the
      network scales as the logarithm of the number of nodes in the network. At T=0 the
      two networks have an opposite behavior: the bosonic network remains very
      clusterized (the distance from the origin remains constant as the network
      increases the number of nodes), while the fermionic network grows following a
      single branch of the tree, and the distance from the origin varies as a power law
      of the number of nodes in the network.

PMID- 12786233
TI  - General quantum Brownian motion with initially correlated and nonlinearly coupled
      environment.
AB  - The dynamics of an open quantum system exhibiting the quantum Brownian motion is
      analyzed when the coupling between the system and its environment is nonlinear,
      and the system and the reservoir are initially correlated. For couplings
      quadratic in the environment variables, the influence functional for the system
      is obtained perturbatively up to second order in the coupling constant, and then
      the propagator is explicitly evaluated when the particle is under the influence
      of a harmonic potential and an additional anharmonic potential, the so-called
      washboard potential. As an application of the propagator, the master equation and
      the Wigner equation are obtained for the quantum Brownian particle moving in a
      harmonic potential for the generalized correlated initial condition, and then for
      the specific case of the simplified "thermal" initial condition. The system is
      shown to obey the corresponding fluctuation-dissipation theorem.

PMID- 12786234
TI  - Critical dynamics of the Gaussian model with multispin transitions.
AB  - In this paper, we present a multispin transition mechanism, which is an extension
      of the Glauber one, to investigate critical dynamics. By exactly solving the
      master equation, the influence of the multispin transition mechanism on the
      dynamic critical behavior is studied for the Gaussian model with nearest-neighbor
      interactions on d-dimensional lattices (d=1, 2, and 3). The time evolution of
      magnetization is exactly calculated, and the exact results of relaxation time and
      dynamic critical exponent are obtained. Our models are divided into two kinds:
      one is the spin-cluster transition and the other is the arbitrary multispin
      transition. It is found that there are different relaxation times, but the same
      dynamical critical exponent for different kinds of multispin transitions. The
      results show that the dynamical critical exponents are independent of spatial
      dimensions and configurations of transitional spins, and that the dynamical
      critical exponent is the same as that of the Glauber dynamics, and thus give a
      strong support to the simple single-spin-transition dynamics. Finally, we give a
      brief discussion on the results.

PMID- 12786235
TI  - Friction effects and clogging in a cellular automaton model for pedestrian
      dynamics.
AB  - We investigate the role of conflicts in pedestrian traffic, i.e., situations
      where two or more people try to enter the same space. Therefore a recently
      introduced cellular automaton model for pedestrian dynamics is extended by a
      friction parameter mu. This parameter controls the probability that the movement
      of all particles involved in a conflict is denied at one time step. It is shown
      that these conflicts are not an undesirable artifact of the parallel update
      scheme, but are important for a correct description of the dynamics. The friction
      parameter mu can be interpreted as a kind of an internal local pressure between
      the pedestrians which becomes important in regions of high density, occurring,
      e.g., in panic situations. We present simulations of the evacuation of a large
      room with one door. It is found that friction has not only quantitative effects,
      but can also lead to qualitative changes, e.g., of the dependence of the
      evacuation time on the system parameters. We also observe similarities to the
      flow of granular materials, e.g., arching effects.

PMID- 12786236
TI  - Diffusion-limited reaction for the one-dimensional trap system.
AB  - We have previously discussed the one-dimensional multitrap system of finite range
      and found somewhat unexpected result that the larger is the number of imperfect
      traps the higher is the transmission through them. We discuss in this work the
      effect of a small number of such traps arrayed along either a constant or a
      variable finite spatial section. It is shown that under specific conditions, to
      be described in the following, the remarked high transmission may be obtained for
      this case also. Thus, compared to the theoretical large number of traps case
      these results may be experimentally applied to real phenomena.

PMID- 12786237
TI  - Traffic signal synchronization.
AB  - The benefits of traffic signal synchronization are examined within the cellular
      automata approach. The microsimulations of traffic flow are obtained with
      different settings of signal period T and time delay delta. Both numerical
      results and analytical approximations are presented. For undersaturated traffic,
      the green-light wave solutions can be realized. For saturated traffic, the
      correlation among the traffic signals has no effect on the throughput. For
      oversaturated traffic, the benefits of synchronization are manifest only when
      stochastic noise is suppressed.

PMID- 12786238
TI  - Effect of quantum fluctuations in an Ising system on small-world networks.
AB  - We study quantum Ising spins placed on small-world networks. A simple model is
      considered in which the coupling between any given pair of spins is a nonzero
      constant if they are linked in the small-world network, and zero otherwise. By
      applying a transverse magnetic field, we have investigated the effect of quantum
      fluctuations. Our numerical analysis shows that the quantum fluctuations do not
      alter the universality class at the ferromagnetic phase transition, which is of
      the mean-field type. The transition temperature is reduced by the quantum
      fluctuations and eventually vanishes at the critical transverse field Delta(c).
      With increasing rewiring probability, Delta(c) is shown to be enhanced.

PMID- 12786239
TI  - Bifurcation and stability analysis of rotating chemical spirals in circular
      domains: boundary-induced meandering and stabilization.
AB  - Recent experimental and model studies have revealed that the domain size may
      strongly influence the dynamics of rotating spirals in two-dimensional pattern
      forming chemical reactions. Hartmann et al. [Phys. Rev. Lett. 76, 1384 (1996)],
      report a frequency increase of spirals in circular domains with diameters
      substantially smaller than the spiral wavelength in a large domain for the
      catalytic NO+CO reaction on a microstructured platinum surface. Accompanying
      simulations with a simple reaction-diffusion system reproduced the behavior.
      Here, we supplement these studies by a numerical bifurcation and stability
      analysis of rotating spirals in a simple activator-inhibitor model. The problem
      is solved in a co-rotating frame of reference. No-flux conditions are imposed at
      the boundary of the circular domain. At large domain sizes, eigenvalues and
      eigenvectors very close to those corresponding to infinite medium translational
      invariance are observed. Upon decrease of domain size, we observe a simultaneous
      change in the rotation frequency and a deviation of these eigenvalues from being
      neutrally stable (zero real part). The latter phenomenon indicates that the
      translation symmetry of the spiral solution is appreciably broken due to the
      interaction with the (now nearby) wall. Various dynamical regimes are found:
      first, the spiral simply tries to avoid the boundary and its tip moves towards
      the center of the circular domain corresponding to a negative real part of the
      "translational" eigenvalues. This effect is noticeable at a domain radius of
      R<R(cr,1). The spiral subsequently exhibits an oscillatory instability: the tip
      trajectory displays a meandering motion, which may be characterized as boundary
      induced spiral meandering. A systematic study of the spiral rotation as a
      function of a control parameter and the domain size reveals that the meandering
      instability in large domains becomes suppressed, and the spiral rotation becomes
      rigid, at a critical radius R(cr,0). Boundary-induced meandering arises below a
      second critical radius R(cr,2)<R(cr,0).

PMID- 12786240
TI  - Scaling and nonscaling finite-size effects in the Gaussian and the mean spherical
      model with free boundary conditions.
AB  - We calculate finite-size effects of the Gaussian model in a Lx(d-1) box geometry
      with free boundary conditions in one direction and periodic boundary conditions
      in d-1 directions for 2<d<4. We also consider film geometry (L--> infinity ).
      Finite-size scaling is found to be valid for d<3 and d>3 but logarithmic
      deviations from finite-size scaling are found for the free energy and energy
      density at the Gaussian upper borderline dimension d*=3. The logarithms are
      related to the vanishing critical exponent 1-alpha-nu=(d-3)/2 of the Gaussian
      surface energy density. The latter has a cusplike singularity in d>3 dimensions.
      We show that these properties are the origin of nonscaling finite-size effects in
      the mean spherical model with free boundary conditions in d > or =3 dimensions.
      At bulk T(c), in d=3 dimensions we find an unexpected nonlogarithmic violation of
      finite-size scaling for the susceptibility chi approximately L3 of the mean
      spherical model in film geometry, whereas only a logarithmic deviation chi
      approximately L2 ln L exists for box geometry. The result for film geometry is
      explained by the existence of the lower borderline dimension d(l)=3, as implied
      by the Mermin-Wagner theorem, that coincides with the Gaussian upper borderline
      dimension d*=3. For 3<d<4 we find a power-law violation of scaling chi
      approximately L(d-1) at bulk T(c) for box geometry and a nonscaling temperature
      dependence chi(surface) approximately xi(d) of the surface susceptibility above
      T(c). For 2<d<3 dimensions we show the validity of universal finite-size scaling
      for the susceptibility of the mean spherical model with free boundary conditions
      for both box and film geometry and calculate the corresponding universal scaling
      functions for T > or =T(c).

PMID- 12786241
TI  - Winning combinations of history-dependent games.
AB  - The Parrondo effect describes the seemingly paradoxical situation in which two
      losing games can, when combined, become a winning game [Parrondo, Harmer, and
      Abbott, Phys. Rev. Lett. 85, 24 (2000)]. Here, we generalize this analysis to the
      case where both games are history dependent, i.e., there is an intrinsic memory
      in the dynamics of each game. Results are presented for the cases of both random
      and periodic switching between the two games.

PMID- 12786242
TI  - Magnetization distribution in the transverse Ising chain with energy flux.
AB  - The zero-temperature transverse Ising chain carrying an energy flux j(E) is
      studied with the aim of determining the nonequilibrium distribution functions,
      P(M(z)) and P(Mx) of its transverse and longitudinal magnetizations,
      respectively. An exact calculation reveals that P(M(z)) is a Gaussian both at
      j(E)=0 and at j(E) not equal to 0, and the width of the distribution decreases
      with increasing energy flux. The distribution of the order-parameter
      fluctuations, P(Mx), is evaluated numerically for spin chains of up to 20 spins.
      For the equilibrium case (j(E)=0), we find the expected Gaussian fluctuations
      away from the critical point, while the critical order-parameter fluctuations are
      shown to be non-Gaussian with a scaling function Phi(x)=Phi(M(x)/<Mx>)=<Mx>P(Mx)
      strongly dependent on the boundary conditions. When j(E) not equal to 0, the
      system displays long-range, oscillating correlations but P(Mx) is a Gaussian
      nevertheless, and the width of the Gaussian decreases with increasing j(E). In
      particular, we find that, at critical transverse field, the width has a j(
      3/8)(E) asymptotic in the j(E)-->0 limit.

PMID- 12786243
TI  - Simulation of hysteresis in magnetic nanoparticles with Nose thermostating.
AB  - The magnetic hysteresis of a two-dimensional lattice of rotors with four-way
      anisotropy interaction and a Heisenberg exchange interaction is studied. The
      Hamiltonian dynamics of the lattice is thermostated using the Nose thermostat,
      resulting in a system that approaches thermal equilibrium and which under certain
      conditions can remain in metastable states. Using physically realistic values for
      the interactions in a nanoparticle of monolayer thickness, we locate the Curie
      temperature of our lattice by determining the peak of the heat capacity curve. We
      then compare the coercive field of our two-dimensional lattice below this Curie
      temperature to the coercive field of an elliptical cobalt nanoparticle measured
      in experiment. We find an order of magnitude agreement between our lattice model
      and the experimental results, even though the value of the anisotropy used is
      more appropriate for a monolayer film than for the nanoparticle.

PMID- 12786244
TI  - Limit of small exits in open Hamiltonian systems.
AB  - The nature of open Hamiltonian systems is analyzed, when the size of the exits
      decreases and tends to zero. Fractal basins appear typically in open Hamiltonian
      systems, but we claim that in the limit of small exits, the invariant sets tend
      to fill up the whole phase space with the strong consequence that a new kind of
      basin appears, where the unpredictability grows indefinitely. This means that for
      finite, arbitrarily small accuracy, we can find uncertain basins, where any
      information about the future of the system is lost. This total indeterminism had
      only been reported in dissipative systems, in particular in the so-called
      intermingled riddled basins, as well as in the riddledlike basins. We show that
      this peculiar, behavior is a general feature of open Hamiltonian systems.

PMID- 12786245
TI  - Disclinations in square and hexagonal patterns.
AB  - We report the observation of defects with fractional topological charges
      (disclinations) in square and hexagonal patterns as numerical solutions of
      several generic equations describing many pattern-forming systems: Swift
      Hohenberg equation, damped Kuramoto-Sivashinsky equation, as well as nonlinear
      evolution equations describing large-scale Rayleigh-Benard and Marangoni
      convection in systems with thermally nearly insulated boundaries. It is found
      that disclinations in square and hexagonal patterns can be stable when nucleated
      from special initial conditions. The structure of the disclinations is analyzed
      by means of generalized Cross-Newell equations.

PMID- 12786246
TI  - Mechanism for the intermittent route to strange nonchaotic attractors.
AB  - Intermittent strange nonchaotic attractors (SNAs) appear typically in
      quasiperiodically forced period-doubling systems. As a representative model, we
      consider the quasiperiodically forced logistic map and investigate the mechanism
      for the intermittent route to SNAs using rational approximations to the
      quasiperiodic forcing. It is found that a smooth torus transforms into an
      intermittent SNA via a phase-dependent saddle-node bifurcation when it collides
      with a new type of "ring-shaped" unstable set.

PMID- 12786247
TI  - Dynamical properties of the synchronization transition.
AB  - We use spreading dynamics to study the synchronization transition (ST) of one
      dimensional coupled map lattices (CML's). Recently, Baroni et al. [Phys. Rev. E
      63, 036226 (2001)] have shown that the ST belongs to the directed percolation
      (DP) universality class for discontinuous CML's. This was confirmed by accurate
      numerical simulations for the Bernoulli map by Ahlers and Pikovsky [Phys. Rev.
      Lett. 88, 254101 (2002)]. Spreading dynamics confirms such an identification only
      for random synchronized states. For homogeneous synchronized states the spreading
      exponents eta and delta are different from the DP exponents but their sum equals
      the corresponding sum of the DP exponents. Such a relation is typical of models
      with infinitely many absorbing states. Moreover, we calculate the spreading
      exponents for the tent map for which the ST belongs to the bounded Kardar-Parisi
      Zhang (BKPZ) universality class. The estimation of spreading exponents for random
      synchronized states is consistent with the hyperscaling relation, while it is
      inconsistent for the homogeneous ones. Finally, we examine the asymmetric tent
      map. For small asymmetry the ST remains of the BKPZ type. However, for large
      asymmetry a different critical behavior appears, with exponents being relatively
      close to those for DP.

PMID- 12786248
TI  - Analytical and numerical investigations of the phase-locked loop with time delay.
AB  - We derive the normal form for the delay-induced Hopf bifurcation in the first
      order phase-locked loop with time delay by the multiple scaling method. The
      resulting periodic orbit is confirmed by numerical simulations. Further detailed
      numerical investigations demonstrate exemplarily that this system reveals a rich
      dynamical behavior. With phase portraits, Fourier analysis, and Lyapunov spectra
      it is possible to analyze the scaling properties of the control parameter in the
      period-doubling scenario, both qualitatively and quantitatively. Within the
      numerical accuracy there is evidence that the scaling constant of the time
      delayed phase-locked loop coincides with the Feigenbaum constant delta
      approximately 4.669 in one-dimensional discrete systems.

PMID- 12786249
TI  - Mean flow and spiral defect chaos in Rayleigh-Benard convection.
AB  - We describe a numerical procedure to construct a modified velocity field that
      does not have any mean flow. Using this procedure, we present two results. First,
      we show that, in the absence of the mean flow, spiral defect chaos collapses to a
      stationary pattern comprising textures of stripes with angular bends. The
      quenched patterns are characterized by mean wave numbers that approach those
      uniquely selected by focus-type singularities, which, in the absence of the mean
      flow, lie at the zigzag instability boundary. The quenched patterns also have
      larger correlation lengths and are comprised of rolls with less curvature.
      Secondly, we describe how the mean flow can contribute to the commonly observed
      phenomenon of rolls terminating perpendicularly into lateral walls. We show that,
      in the absence of the mean flow, rolls begin to terminate into lateral walls at
      an oblique angle. This obliqueness increases with the Rayleigh number.

PMID- 12786250
TI  - Noise-sustained structures in differential-flow reactors with autocatalytic
      kinetics.
AB  - We have studied the formation of noise-sustained structures in a differential
      flow reactor with cubic autocatalytic kinetics (the Gray-Scott model). In this
      system the interplay between advection, diffusion, reaction, and noise
      fluctuations leads to the formation of noise-sustained patterns in the key
      species. Numerical integration in one and two spatial dimensions shows that the
      structures are nonlocally cross correlated. Near threshold, the observed
      correlation is related to the properties of the convectively unstable critical
      modes.

PMID- 12786251
TI  - Mode transitions and wave propagation in a driven-dissipative Toda-Rayleigh ring.
AB  - A circular lattice (ring) of N electronic elements with Toda-type exponential
      interactions and Rayleigh-type dissipation is used to illustrate wave formation,
      propagation, and switching between wave modes. A methodology is provided to help
      controlling modes, thus allowing it to realize any of (N-1) different wave modes
      (including soliton-type modes) and the switching between them by means of a
      single control parameter.

PMID- 12786252
TI  - Quantum phase transition in the Frenkel-Kontorova chain: from pinned instanton
      glass to sliding phonon gas.
AB  - We study analytically and numerically the one-dimensional quantum Frenkel
      Kontorova chain in the regime where the classical model is located in the pinned
      phase characterized by the gaped phonon excitations and devil's staircase. By
      extensive quantum Monte Carlo simulations, we show that for the effective Planck
      constant Planck smaller than the critical value Planck(c) the quantum chain is in
      the pinned instanton glass phase. In this phase, the elementary excitations have
      two branches: phonons, separated from zero energy by a finite gap, and instantons
      that have an exponentially small excitation energy. At Planck = Planck(c) the
      quantum phase transition takes place and for Planck > Planck(c) the pinned
      instanton glass is transformed into the sliding phonon gas with gapless phonon
      excitations. This transition is accompanied by the divergence of the spatial
      correlation length and appearance of sliding modes at Planck > Planck(c).

PMID- 12786253
TI  - Scattering and separators in dissipative systems.
AB  - Scattering of particlelike patterns in dissipative systems is studied, especially
      we focus on the issue how the input-output relation is controlled at a head-on
      collision in the one-dimensional(1D) space where traveling pulses interact
      strongly. It remains an open problem due to the large deformation of patterns at
      a colliding point. We found that a special type of steady or time-periodic
      solutions called separators and their stable and unstable manifolds direct the
      traffic flow of orbits. Such separators are, in general, highly unstable even in
      the 1D case which causes a variety of input-output relations through the
      scattering process. We illustrate the ubiquity of separators by using the Gray
      Scott model and a three-component reaction diffusion model arising in gas
      discharge phenomena.

PMID- 12786254
TI  - Traveling waves in phase-separating reactive mixtures.
AB  - A model of phase separation of chemically reactive ternary mixtures is
      constructed. In this model, spatially periodic structures that coherently
      propagate at a constant speed emerge through a Hopf bifurcation at a finite wave
      number. It is shown by computer simulations that both lamellar and hexagonal
      structures undergo a coherent propagating motion in two dimensions, and there are
      two types of traveling hexagons depending on the relative direction between the
      traveling velocity and the lattice vectors of the hexagonal structure. Amplitude
      equations for the traveling waves are derived, and the stability of the traveling
      and standing waves is discussed.

PMID- 12786255
TI  - Phase synchronization in the perturbed Chua circuit.
AB  - We show experimental and numerical results of phase synchronization between the
      chaotic Chua circuit and a small sinusoidal perturbation. Experimental real-time
      phase synchronized states can be detected with oscilloscope visualization of the
      attractor, using specific sampling rates. Arnold tongues demonstrate robust phase
      synchronized states for perturbation frequencies close to the characteristic
      frequency of the unperturbed Chua.

PMID- 12786256
TI  - Bifurcation diagram of a complex delay-differential equation with cubic
      nonlinearity.
AB  - We reduce the Lang-Kobayashi equations for a semiconductor laser with external
      optical feedback to a single complex delay-differential equation in the long
      delay-time limit. The reduced equation has a time-delayed linear term and a cubic
      instantaneous nonlinearity. There are only two parameters, the real linewidth
      enhancement factor and the complex feedback strength. The equation displays a
      very rich dynamics and can sustain steady, periodic, quasiperiodic, and chaotic
      regimes. We study the steady solutions analytically and analyze the periodic
      solutions by using a numerical continuation method. This leads to a bifurcation
      diagram of the steady and periodic solutions, stable and unstable. We illustrate
      the chaotic regimes by a direct numerical integration and show that low frequency
      fluctuations still occur.

PMID- 12786257
TI  - Information flow and nontrivial collective behavior in chaotic-coupled-map
      lattices.
AB  - This work quantitatively demonstrates a nontrivial collective behavior, which
      depends on the coupling strength in chaotic-coupled-map lattices, using the
      interdependence measure emerging from a local unit. The amount of information
      flow which flows from the instantaneous mean field to a local map has been
      investigated using the time-delayed mutual information. Interestingly, the
      collective system's behavior is found to be associated with the amount of
      information flow. As mentioned above, both methods can effectively display the
      nontrivial collective behavior and the amount of information flow.

PMID- 12786258
TI  - Receptors as a master key for synchronization of rhythms.
AB  - A simple, but general, scheme to achieve synchronization of rhythms is proposed.
      It can handle both external synchronization and self-synchronization within a
      single mathematical framework. In this scheme, external linear stimulations can
      be converted into internal nonlinear stimulations by the mathematical model
      receptor without breaking the regular motions of limit cycle oscillators. Thus,
      even a small external periodic stimulation can work very efficiently for
      achieving synchronization. Stimulation via model receptors is much more effective
      for synchronization than mechanically forced stimulations, and the phenomenon
      called N:M phase locking (N not equal to 1, M not equal to 1) can be suppressed
      in the weak coupling domain, too.

PMID- 12786259
TI  - Direct observation of homoclinic orbits in human heart rate variability.
AB  - Homoclinic trajectories of the interbeat intervals between contractions of
      ventricles of the human heart are identified. The interbeat intervals are
      extracted from 24-h Holter ECG recordings. Three such recordings are discussed in
      detail. Mappings of the measured consecutive interbeat intervals are constructed.
      In the second and in some cases in the fourth iterate of the map of interbeat
      intervals homoclinic trajectories associated with a hyperbolic saddle are found.
      The homoclinic trajectories are often persistent for many interbeat intervals,
      sometimes spanning many thousands of heartbeats. Several features typical for
      homoclinic trajectories found in other systems were identified, including a
      signature of the gluing bifurcation. The homoclinic trajectories are present both
      in recordings of heart rate variability obtained from patients with an increased
      number of arrhythmias and in cases in which the sinus rhythm is dominant. The
      results presented are a strong indication of the importance of deterministic
      nonlinear instabilities in human heart rate variability.

PMID- 12786260
TI  - Loschmidt echo and Lyapunov exponent in a quantum disordered system.
AB  - We investigate the sensitivity of a disordered system with diffractive scatterers
      to a weak external perturbation. Specifically, we calculate the fidelity M(t)
      (also called the Loschmidt echo) characterizing a return probability after a
      propagation for a time t followed by a backward propagation governed by a
      slightly perturbed Hamiltonian. For short-range scatterers, we perform a
      diagrammatic calculation showing that the fidelity decays first exponentially
      according to the golden rule, and then follows a power law governed by the
      diffusive dynamics. For long-range disorder (when the diffractive scattering is
      of small-angle character), an intermediate regime emerges where the diagrammatics
      is not applicable. Using the path-integral technique, we derive a kinetic
      equation and show that M(t) decays exponentially with a rate governed by the
      classical Lyapunov exponent.

PMID- 12786261
TI  - Evidence for directed percolation universality at the onset of spatiotemporal
      intermittency in coupled circle maps.
AB  - We consider a lattice of coupled circle maps, a popular model for the study of
      mode-locked phenomena. We find that the onset of spatiotemporal intermittency
      (STI) in this system is analogous to directed percolation (DP), with the
      transition being to a unique absorbing state for low nonlinearities, and to
      weakly chaotic absorbing states for high nonlinearities. We find that the
      complete set of static exponents and spreading exponents at all critical points
      match those of DP very convincingly. Further, hyperscaling relations are
      fulfilled, leading to independent controls and consistency checks of the values
      of all the critical exponents. These results provide an example in support of the
      conjecture that the onset of STI in deterministic models belongs to the DP
      universality class. Nonuniversal spreading exponents are seen only for the cases
      where the initial state is homogeneous with symmetrically placed seeds leading to
      strictly symmetric spreading. However, very small departures from homogeneity are
      sufficient to restore the DP exponents.

PMID- 12786262
TI  - Delay-induced synchronization phenomena in an array of globally coupled logistic
      maps.
AB  - We study the synchronization of a linear array of globally coupled identical
      logistic maps. We consider a time-delayed coupling that takes into account the
      finite velocity of propagation of the interactions. We find globally synchronized
      states in which the elements of the array evolve along a periodic orbit of the
      uncoupled map, while the spatial correlation along the array is such that an
      individual map sees all other maps in his present, current, state. For values of
      the nonlinear parameter such that the uncoupled maps are chaotic, time-delayed
      mutual coupling suppresses the chaotic behavior by stabilizing a periodic orbit
      that is unstable for the uncoupled maps. The stability analysis of the
      synchronized state allows us to calculate the range of the coupling strength in
      which global synchronization can be obtained.

PMID- 12786263
TI  - Noise-covered drift bifurcation of dissipative solitons in a planar gas-discharge
      system.
AB  - The trajectories of propagating self-organized, well-localized solitary patterns
      (dissipative solitons) in the form of electrical current filaments are
      experimentally investigated in a planar quasi-two-dimensional dc gas-discharge
      system with high Ohmic semiconductor barrier. Earlier phenomenological models
      qualitatively describing the experimental observations in terms of a particle
      model predict a transition from stationary filaments to filaments traveling with
      constant finite speed due to an appropriate change of the system parameters. This
      prediction motivates a search for a drift bifurcation in the experimental system,
      but a direct comparison of experimentally recorded trajectories with theoretical
      predictions is impossible due to the strong influence of noise. To solve this
      problem, the filament dynamics is modeled using an appropriate Langevin equation,
      allowing for the application of a stochastic data analysis technique to separate
      deterministic and stochastic parts of the dynamics. Simulations carried out with
      the particle model demonstrate the efficiency of the method. Applying the
      technique to the experimentally recorded trajectories yields good agreement with
      the predictions of the model equations. Finally, the predicted drift bifurcation
      is found using the semiconductor resistivity as control parameter. In the
      resulting bifurcation diagram, the square of the equilibrium velocity scales
      linearly with the control parameter.

PMID- 12786264
TI  - Control of chaos by capture and release.
AB  - We propose and demonstrate a different method for the control of flip saddles in
      dissipative chaotic systems. Due to the dynamics of a flip saddle, the stable
      manifolds of a target orbit and its perturbation can be modeled as a pair of
      concentric Mobius bands. Over the period of the target orbit, these bands rotate
      relative to one another. The method of capture and release (CR) takes advantage
      of this rotation, and captures a nearby system state in the perturbed stable
      manifold, releasing it when the rotation of the Mobius bands brings them into
      alignment. Unlike the method of Ott, Grebogi, and Yorke and most of its variants,
      CR does not rely on the unstable component of the flow to push the system state
      onto the stable manifold; the system state is evolving in a stable subspace for
      the duration of the control perturbation.

PMID- 12786265
TI  - Stochastic resonance on two-dimensional arrays of bistable oscillators in a
      nonlinear optical system.
AB  - We describe an experimental realization of stochastic resonance in two
      dimensional arrays of coupled nonlinear oscillators. The experiment is
      implemented using an optoelectronic system composed of a liquid crystal light
      valve in a feedback loop with external, spatially variable noise being added
      through a liquid crystal display. The behavior of the system differs from
      previously studied uniform arrays, showing a high signal-to-noise ratio at the
      output for a broad range of input noise. We show that this behavior is
      qualitatively the same as that exhibited by computer models where the nonlinear
      elements of the array have a distribution of biases applied to their switching
      thresholds.

PMID- 12786266
TI  - Brightened single-bubble sonoluminescence by phase-adjusted high-frequency
      acoustic pulse.
AB  - This paper experimentally and numerically studies the effect of a high-frequency
      acoustic pulse on brightening single-bubble sonoluminescence (SBSL). A
      polyvinylidene fluoride point-focusing transducer was driven by a 700-W pulse
      generator to superimpose the acoustic pulse on the sonoluminescing bubble. The
      center frequency of the pulse was 10 MHz and the duration was 0.15 micros. The
      pulse was triggered every 100 cycles of the low-frequency standing wave used to
      make SBSL. The intensity of SBSL was measured as a function of time lag of
      superimposed pulse. Only the pulse that arrived at the bubble at the early
      growing stage could increase the brightness. This trend was confirmed with a
      numerical calculation based on the Rayleigh-Plesset equation. The increased
      brightness reached 300% of those of the classical SBSL flashes when the time lag
      was correctly adjusted.

PMID- 12786267
TI  - Pumping of liquids with ac voltages applied to asymmetric pairs of
      microelectrodes.
AB  - The net flow of electrolyte induced by an ac electric potential applied to an
      array of asymmetric pairs of microelectrodes has recently been reported. The
      interaction between the oscillating electric field and the oscillating induced
      charge at the diffuse double layer on the electrodes results in a steady electro
      osmotic velocity distribution on top of the electrodes. This slip velocity
      distribution is anisotropic and produces a net flow of fluid. This paper presents
      a theoretical analysis of the pumping phenomena based upon an electro-osmotic
      model in ac fields. The electrical equations are solved numerically using the
      charge simulation method. The bulk flow generated by the electro-osmotic slip
      velocity is calculated. The dependence of the fluid flow on voltage and frequency
      is described and compared to experiments.

PMID- 12786268
TI  - Flow in a rotating curved circular pipe.
AB  - The flow in a rotating curved pipe with circular cross section is investigated
      theoretically and numerically. A perturbation solution up to the second order is
      obtained. A numerical procedure is used to solve the full governing equations and
      the simplified governing equations in the small curvature limit. Comparisons are
      made between the numerical and perturbation results, elucidating the lost
      information due to simplification and the valid range of the perturbation
      solution. The flow characteristics, including the secondary flow, the axial flow,
      and the friction factor ratio, are examined in detail.

PMID- 12786269
TI  - Linearized stability analysis of accelerated planar and spherical fluid
      interfaces with slow compression.
AB  - We present linearized stability analyses of the effect of slow anisotropic
      compression or expansion on the growth of perturbations at accelerated fluid
      interfaces in both planar and spherical geometries. The interface separates two
      fluids with different densities, compressibilities, and compression rates. We
      show that a perturbation of large mode number on a spherical interface grows at
      precisely the same rate as a similar perturbation on a planar interface subjected
      to the same normal and transverse compression rates.

PMID- 12786270
TI  - Onset of turbulence in accelerated high-Reynolds-number flow.
AB  - A new criterion, flow drive time, is identified here as a necessary condition for
      transition to turbulence in accelerated, unsteady flows. Compressible, high
      Reynolds-number flows initiated, for example, in shock tubes, supersonic wind
      tunnels with practical limitations on dimensions or reservoir capacity, and high
      energy density pulsed laser target vaporization experimental facilities may not
      provide flow duration adequate for turbulence development. In addition, for
      critical periods of the overall flow development, the driving background flow is
      often unsteady in the experiments as well as in the physical flow situations they
      are designed to mimic. In these situations transition to fully developed
      turbulence may not be realized despite achievement of flow Reynolds numbers
      associated with or exceeding stationary flow transitional criteria. Basically our
      transitional criterion and prediction procedure extends to accelerated, unsteady
      background flow situations the remarkably universal mixing transition criterion
      proposed by Dimotakis [P. E. Dimotakis, J. Fluid Mech. 409, 69 (2000)] for
      stationary flows. This provides a basis for the requisite space and time scaling.
      The emphasis here is placed on variable density flow instabilities initiated by
      constant acceleration Rayleigh-Taylor instability (RTI) or impulsive (shock)
      acceleration Richtmyer-Meshkov instability (RMI) or combinations of both. The
      significant influences of compressibility on these developing transitional flows
      are discussed with their implications on the procedural model development. A
      fresh perspective for predictive modeling and design of experiments for the
      instability growth and turbulent mixing transitional interval is provided using
      an analogy between the well-established buoyancy-drag model with applications of
      a hierarchy of single point turbulent transport closure models. Experimental
      comparisons with the procedural results are presented where use is made of three
      distinctly different types of acceleration driven instability experiments: (1)
      classical, relatively low speed, constant acceleration RTI experiments; (2) shock
      tube, shockwave driven RMI flow mixing experiments; (3) laser target vaporization
      RTI and RMI mixing experiments driven at very high energy density. These last
      named experiments are of special interest as they provide scaleable flow
      conditions simulating those of astrophysical magnitude such as shock-driven
      hydrodynamic mixing in supernova evolution research.

PMID- 12786271
TI  - Velocity fluctuations and dispersion in a simple porous medium.
AB  - We model a fluid-filled disordered porous medium by a lattice-Boltzmann system
      with randomly broken links. The broken links exert a friction on the fluid
      without excluding volume. Such a model closely mimics the idealized picture of a
      porous medium, which is often used in the theoretical analysis of hydrodynamic
      dispersion. We find that the Brinkman equation describes both the mean flow
      characteristics and the spatial decay of velocity fluctuations in the system.
      However, the temporal decay of the velocity correlations (that a particle
      experiences as it moves with the fluid), cannot be simply related to the spatial
      decay. It is this temporal decay that determines the dispersivity. Thus,
      hydrodynamic dispersion is generally greater than theories based on spatial
      correlations would imply. This is particularly true at high densities, where such
      theories considerably underestimate both the magnitude and transient time scale
      for dispersion. Nonetheless, temporal velocity correlations are still ultimately
      screened and the hydrodynamic dispersion coefficient converges exponentially. The
      long-lived transients reported for more realistic systems must therefore be due
      explicitly to the presence of excluded volume.

PMID- 12786272
TI  - Experimental studies of occupation times in turbulent flows.
AB  - The motion of passively convected particles in turbulent flows is studied
      experimentally in approximately homogeneous and isotropic turbulent flows,
      generated in water by two moving grids. The simultaneous trajectories of many
      small passively convected, neutrally buoyant, polystyrene particles are followed
      in time by a particle tracking technique. We estimate the probability
      distribution of the occupation times of such particles in spherical volumes with
      a given radius. A self-consistently moving particle defines the center of the
      reference sphere, with the occupation time being defined as the difference
      between entrance and exit times of surrounding particles convected through the
      sphere by the turbulent motions. Simple, and seemingly universal, scaling laws
      are obtained for the probability density of the occupation times in terms of the
      basic properties for the turbulent flow and the geometry. In the present
      formulation, the results of the analysis are relevant for understanding details
      in the feeding rate of micro-organisms in turbulent waters, for instance.

PMID- 12786273
TI  - Anomalous roughening in experiments of interfaces in Hele-Shaw flows with strong
      quenched disorder.
AB  - We report experimental evidence of anomalous kinetic roughening in the stable
      displacement of an oil-air interface in a Hele-Shaw cell with strong quenched
      disorder. The disorder consists of a random modulation of the gap spacing that is
      transverse to the growth direction (tracks). Experiments were performed by
      varying the average interface velocity and the gap spacing, and measuring the
      scaling exponents. The following values of the scaling exponents were obtained;
      beta approximately 0.50, beta* approximately 0.25, alpha approximately 1.0,
      alpha(loc) approximately 0.5, and z approximately 2. When there is no fluid
      injection, the interface is driven solely by capillary forces, and a higher value
      of beta of approximately beta=0.65 is measured. The presence of multiscaling and
      the particular morphology of the interfaces, characterized by large height
      differences that follow a Levy distribution, confirms the existence of anomalous
      scaling. From a detailed study of the motion of the oil-air interface, we show
      that the anomaly is a consequence of different local velocities on the tracks
      plus the coupling in the motion between neighboring tracks. The anomaly
      disappears at high interface velocities, weak capillary forces, or when the
      disorder is not sufficiently persistent in the growth direction. We have also
      observed the absence of scaling when the disorder is very strong or when a
      regular modulation of the gap spacing is introduced.

PMID- 12786274
TI  - Screw dynamo in a time-dependent pipe flow.
AB  - The kinematic dynamo problem is investigated for the flow of a conducting fluid
      in a cylindrical, periodic tube with conducting walls. The methods used are an
      eigenvalue analysis of the steady regime, and the three-dimensional solution of
      the time-dependent induction equation. The configuration and parameters
      considered here are close to those of a dynamo experiment planned in Perm, which
      will use a torus-shaped channel. We find growth of an initial magnetic field by
      more than three orders of magnitude. A marked field growth can be obtained if the
      braking time is less than 0.2 s and only one diverter is used in the channel. The
      structure of the seed field has a strong impact on the field amplification
      factor. Generation properties can be improved by adding ferromagnetic particles
      to the fluid in order to increase its relative permeability, but this will not be
      necessary for the success of the dynamo experiment. For higher magnetic Reynolds
      numbers, the nontrivial evolution of different magnetic modes limits the value of
      simple "optimistic" and "pessimistic" estimates.

PMID- 12786275
TI  - Harmonic enhancement of single-bubble sonoluminescence.
AB  - It is known from experiment that the light emission from a sonoluminescing bubble
      can be increased by using more than one driving frequency. In this paper, a
      systematic method to determine the optimal conditions of pressure amplitude and
      relative phase for this effect is described. As a specific application, a two
      frequency system--26.5 kHz and 53 kHz--is considered. It is found that the
      maximum temperatures achievable can be appreciably increased with respect to
      single-frequency drive, still maintaining spherical stability, provided the
      dissolved inert gas concentration is kept extremely low in order to maintain
      diffusive stability.

PMID- 12786276
TI  - Tolman's nonlinearity of capillary waves.
AB  - A nonlinear theory of nanometer capillary waves is developed that takes curvature
      dependence of the surface tension coefficient (Tolman's nonlinearity) into
      account. Estimations are given that indicate the importance of Tolman's
      nonlinearity for thermocapillary waves.

PMID- 12786277
TI  - Drag reduction by polymers in turbulent channel flows: Energy redistribution
      between invariant empirical modes.
AB  - We address the phenomenon of drag reduction by a dilute polymeric additive to
      turbulent flows, using direct numerical simulations (DNS) of the FENE-P model of
      viscoelastic flows. It had been amply demonstrated that these model equations
      reproduce the phenomenon, but the results of DNS were not analyzed so far with
      the goal of interpreting the phenomenon. In order to construct a useful framework
      for the understanding of drag reduction we initiate in this paper an
      investigation of the most important modes that are sustained in the viscoelastic
      and Newtonian turbulent flows, respectively. The modes are obtained empirically
      using the Karhunen-Loeve decomposition, allowing us to compare the most energetic
      modes in the viscoelastic and Newtonian flows. The main finding of the present
      study is that the spatial profile of the most energetic modes is hardly changed
      between the two flows. What changes is the energy associated with these modes,
      and their relative ordering in the decreasing order from the most energetic to
      the least. Modes that are highly excited in one flow can be strongly suppressed
      in the other, and vice versa. This dramatic energy redistribution is an important
      clue to the mechanism of drag reduction as is proposed in this paper. In
      particular, there is an enhancement of the energy containing modes in the
      viscoelastic flow compared to the Newtonian one; drag reduction is seen in the
      energy containing modes rather than the dissipative modes, as proposed in some
      previous theories.

PMID- 12786278
TI  - Flow profile near a wall measured by double-focus fluorescence cross-correlation.
AB  - We present an experimental approach to flow profiling within femtoliter sample
      volumes, which allows the high-precision measurements at the solid interface. The
      method is based on the spatial cross-correlation of the fluorescence response
      from labeled tracer particles (latex nanospheres or single dye molecules). Two
      excitation volumes, separated by a few micrometers, are created by two laser foci
      under a confocal microscope. The velocity of tracer particles is measured in a
      channel about 100 microm wide within a typical accuracy of 0.1%, and the
      positions of the walls are estimated independently of any hydrodynamic data. The
      underlying theory for the optical method is given for an arbitrary velocity
      profile, explicitly presenting the numerical convolutions necessary for a
      quantitative analysis. It is illustrated by using the Poiseuille flow of a
      Newtonian liquid with slip as an example. Our analysis yields a large apparent
      fluid velocity at the wall, which is mostly due to the impact of the colloidal
      (electrostatic) forces. This colloidal lift is crucially important in
      accelerating the transport processes of molecules and nanoparticles in
      microfluidic devices.

PMID- 12786279
TI  - Postbreakthrough behavior in flow through porous media.
AB  - We numerically simulate the traveling time of a tracer in convective flow between
      two points (injection and extraction) separated by a distance r in a model of
      porous media, d=2 percolation. We calculate and analyze the traveling time
      probability density function for two values of the fraction of connecting bonds
      p: the homogeneous case p=1 and the inhomogeneous critical threshold case p=p(c).
      We analyze both constant current and constant pressure conditions at p=p(c). The
      homogeneous p=1 case serves as a comparison base for the more complicated p=p(c)
      situation. We find several regions in the probability density of the traveling
      times for the homogeneous case (p=1) and also for the critical case (p=p(c)) for
      both constant pressure and constant current conditions. For constant pressure,
      the first region I(P) corresponds to the short times before the flow breakthrough
      occurs, when the probability distribution is strictly zero. The second region
      II(P) corresponds to numerous fast flow lines reaching the extraction point, with
      the probability distribution reaching its maximum. The third region III(P)
      corresponds to intermediate times and is characterized by a power-law decay. The
      fourth region IV(P) corresponds to very long traveling times, and is
      characterized by a different power-law decaying tail. The power-law
      characterizing region IV(P) is related to the multifractal properties of flow in
      percolation, and an expression for its dependence on the system size L is
      presented. The constant current behavior is different from the constant pressure
      behavior, and can be related analytically to the constant pressure case. We
      present theoretical arguments for the values of the exponents characterizing each
      region and crossover times. Our results are summarized in two scaling assumptions
      for the traveling time probability density; one for constant pressure and one for
      constant current. We also present the production curve associated with the
      probability of traveling times, which is of interest to oil recovery.

PMID- 12786280
TI  - Marangoni instability of a thin liquid film resting on a locally heated
      horizontal wall.
AB  - Long-wave Marangoni instabilities can be induced thermally on a thin liquid layer
      overlying a horizontal solid substrate with either a uniform or a nonuniform base
      temperature. For a nonuniform base temperature, the film height thickens near the
      region where temperature gradients are negligible and severely thins upstream;
      "fingering" patterns are observed in this region. These states are related to the
      patterns observed in the isothermal case, which are reasonably well understood.
      The stability of these spatiotemporally evolving states to transverse
      disturbances is investigated using a transient growth-type analysis. It is found
      that the band of unstable wave numbers exhibiting growth is strongly dependent on
      the lateral extent of the heating source. Inspection of surface reconstructions
      of the film thickness profiles reveals the existence of three-dimensional
      patterns in the thinning region behind the thickened front.

PMID- 12786281
TI  - Vlasov-Maxwell simulations of high-frequency longitudinal waves in a magnetized
      plasma.
AB  - The plasma response to the injection of a propagating purely electrostatic wave
      of finite amplitude is investigated by means of a kinetic code which solves the
      Vlasov equations for electrons and ions in the three-dimensional (one spatial and
      two in velocity, 1D2V) phase space, self-consistently coupled to the Maxwell
      equations. The plasma is uniformly magnetized, and the wave frequency close to
      the cold upper-hybrid resonance omega(0)=sqrt[omega(2)(pe)+omega(2)(ce)] is
      considered. Coherent structures are formed in the phase space that would be
      completely missed by a hydrodynamic analysis. In particular, in the early stage
      of the interaction, the initially unperturbed equilibrium electron distribution
      is strongly affected as a whole by the pump, taking a ringlike shape in the
      velocity plane transverse to the magnetic field. Then, a sort of instability
      occurs, leading to the broadening and flattening of the electron distribution.

PMID- 12786282
TI  - Weakly dissipative dust-ion-acoustic solitons.
AB  - We investigate the possibility for dust ion-acoustic solitons to exist.
      Compressive solitonlike perturbations are damped and slowed down, mainly due to
      the plasma absorption and ion scattering on microparticles. The perturbations are
      shown to possess the main properties of solitons. There is a principal
      possibility to study experimentally the role of trapped electrons in the soliton
      formation.

PMID- 12786283
TI  - Blast waves produced by interactions of femtosecond laser pulses with water.
AB  - The behaviors of the blast waves produced by femtosecond laser-water
      interactions, and the blast waves induced by laser self-focusing in air, have
      been investigated using optical shadowgraphy at a maximum intensity of 1 x 10(16)
      W/cm(2). The temporal evolution of the blast wave launched by the water plasma
      can be described by a planar blast wave model including source mass. An
      aneurismlike structure, due to the quick propagation inside a hollow channel
      formed by laser self-focusing, is observed. The expansion of the channel in air
      is found to agree with a cylindrical self-similar blast wave solution.

PMID- 12786284
TI  - Intermittency, scaling, and the Fokker-Planck approach to fluctuations of the
      solar wind bulk plasma parameters as seen by the WIND spacecraft.
AB  - The solar wind provides a natural laboratory for observations of
      magnetohydrodynamic (MHD) turbulence over extended temporal scales. Here, we
      apply a model independent method of differencing and rescaling to identify self
      similarity in the probability density functions (PDF) of fluctuations in solar
      wind bulk plasma parameters as seen by the WIND spacecraft. Whereas the
      fluctuations of speed v and interplanetary magnetic field (IMF) magnitude B are
      multifractal, we find that the fluctuations in the ion density rho, energy
      densities B2 and rhov(2) as well as MHD-approximated Poynting flux vB(2) are
      monoscaling on the time scales up to 26 hr. The single curve, which we find to
      describe the fluctuations PDF of all these quantities up to this time scale, is
      non-Gaussian. We model this PDF with two approaches--Fokker-Planck, for which we
      derive the transport coefficients and associated Langevin equation, and the
      Castaing distribution that arises from a model for the intermittent turbulent
      cascade.

PMID- 12786285
TI  - Modeling of self-excited dust vortices in complex plasmas under microgravity.
AB  - A two-dimensional hydrodynamic model for a dusty argon plasma in which the plasma
      and dust parameters are solved self-consistently has been supplemented with a
      separate dust particle tracing module to study the behavior of dust vortices.
      These coherent vortices appear in plasma crystal experiments performed under
      microgravity conditions. The nonconservative total force exerted by the discharge
      on the dust particles is responsible for the generation of the vortices. The
      contribution of the thermophoretic force driven by the gas temperature gradient
      plays an insignificant role in the generation of the vortices, even when the gas
      heating via the dust particles is taken into account. The forces related to the
      electric field, including the ion drag force, are dominant.

PMID- 12786286
TI  - Equation-of-state measurements of polyimide at pressures up to 5.8 TPa using low
      density foam with laser-driven shock waves.
AB  - The laser-driven equation-of-state (EOS) experiments for polyimide are presented.
      The experiments were performed with emission measurements from the rear sides of
      shocked targets at up to a laser intensity of 10(14) W/cm(2) or higher with 351
      nm wavelength and 2.5 ns duration. Polyimide Hugoniot data were obtained up to
      0.6 TPa with good accuracy. Applying low-density foam ablator to the EOS unknown
      material, we also obtained the data at a highest pressure of 5.8 TPa in the
      nonmetal materials. Those data were in agreement with the theoretical curves.

PMID- 12786287
TI  - Electron distribution function in short-pulse photoionization.
AB  - Two well-known limiting regimes of photoionization, when a laser beam interacts
      with a gas, correspond to the tunneling and the multiphoton processes. The latter
      dominates in the low-intensity regime, while the former is appropriate at higher
      intensities. Electrons are born with negligible velocity in tunneling ionization,
      while in l-photon ionization they are born with a fixed energy determined by l,
      the photon energy and the ionization potential of the molecule. The transport
      equation for the distribution function of electrons can be integrated along the
      characteristics defined by the classical equations of motion in the laser field.
      Expressions for the distribution function have been obtained in the two regimes
      using the appropriate analytical form for the ionization rate. Results from two
      dimensional particle-in-cell simulations and illustrative plots of the
      distribution function are presented and discussed.

PMID- 12786288
TI  - Low-pressure diffusion equilibrium of electronegative complex plasmas.
AB  - A self-consistent fluid theory of complex electronegative colloidal plasmas in
      parallel-plate low-pressure discharge is presented. The self-organized low
      pressure diffusion equilibrium is maintained through sources and sinks of
      electrons, positive and negative ions, in plasmas containing dust grains. It is
      shown that the colloidal dust grain subsystem strongly affects the stationary
      state of the discharge by dynamically modifying the electron temperature and
      particle creation and loss processes. The model accounts for ionization,
      ambipolar diffusion, electron and ion collection by the dusts, electron
      attachment, positive-ion-negative-ion recombination, and relevant elastic and
      inelastic collisions. The spatial profiles of electron and positive-ion-negative
      ion number densities, electron temperature, and dust charge in electronegative
      SiH4 discharges are obtained for different grain size, input power, neutral gas
      pressure, and rates of negative-ion creation and loss.

PMID- 12786289
TI  - Two-dimensional effects in laser-created plasmas measured with soft-x-ray laser
      interferometry.
AB  - Soft-x-ray laser interferograms of laser-created plasmas generated at moderate
      irradiation intensities (1 x 10(11)-7 x 10(12) W cm(-2)) with lambda=1.06 microm
      light pulses of approximately 13-ns-FWHM (full width at half maximum) duration
      and narrow focus (approximately 30 microm) reveal the unexpected formation of an
      inverted density profile with a density minimum on axis and distinct plasma
      sidelobes. Model simulations show that this strong two-dimensional hydrodynamic
      behavior is essentially a universal phenomena that is the result of plasma
      radiation induced mass ablation and cooling in the areas surrounding the focal
      spot.

PMID- 12786290
TI  - Lens optics as an optical computer for group contractions.
AB  - It is shown that the one-lens system in para-axial optics can serve as an optical
      computer for contraction of Wigner's little groups and an analog computer that
      transforms analytically computations on a spherical surface to those on a
      hyperbolic surface. It is shown possible to construct a set of Lorentz
      transformations which leads to a 2x2 matrix whose expression is the same as those
      in the para-axial lens optics. It is shown that the lens focal condition
      corresponds to the contraction of the O(3)-like little group for a massive
      particle to the E(2)-like little group for a massless particle, and also to the
      contraction of the O(2,1)-like little group for a spacelike particle to the same
      E(2)-like little group. The lens-focusing transformations presented in this paper
      allow us to continue analytically the spherical O(3) world to the hyperbolic
      O(2,1) world, and vice versa. Since the traditional role of Wigner's little
      groups has been to dictate the internal space-time symmetries of massive,
      massless, and imaginary-mass particles, the one-lens system provides a
      unification of those symmetries.

PMID- 12786291
TI  - Spontaneous formation of dynamical patterns with fractal fronts in the cyclic
      lattice Lotka-Volterra model.
AB  - Dynamical patterns, in the form of consecutive moving stripes or rings, are shown
      to develop spontaneously in the cyclic lattice Lotka-Volterra model, when
      realized on square lattice, at the reaction limited regime. Each stripe consists
      of different particles (species) and the borderlines between consecutive stripes
      are fractal. The interface width w between the different species scales as w(L,t)
      approximately L(alpha)f(t/L(z)), where L is the linear size of the interface, t
      is the time, and alpha and z are the static and dynamical critical exponents,
      respectively. The critical exponents were computed as alpha=0.49+/-0.03 and
      z=1.53+/-0.13 and the propagating fronts show dynamical characteristics similar
      to those of the Eden growth models.

PMID- 12786292
TI  - Numerical simulations of self-focusing of ultrafast laser pulses.
AB  - Simulation of nonlinear propagation of intense ultrafast laser pulses is a hard
      problem, because of the steep spatial gradients and the temporal shocks that form
      during the propagation. In this study we adapt the iterative grid distribution
      method of Ren and Wang [J. Comput. Phys. 159, 246 (2000)] to solve the two
      dimensional nonlinear Schrodinger equation with normal time dispersion, space
      time focusing, and self-steepening. Our simulations show that, after the
      asymmetric temporal pulse splitting, the rear peak self-focuses faster than the
      front one. As a result, the collapse of the rear peak is arrested before that of
      the front peak. Unlike what has sometimes been conjectured, however, collapse of
      the two peaks is not arrested through multiple splittings, but rather through
      temporal dispersion.

PMID- 12786293
TI  - Nonlinear optical effects in a two-dimensional photonic crystal containing one
      dimensional Kerr defects.
AB  - The nonlinear optical effects induced by a one-dimensional (1D) line defect, made
      of Kerr material, in a 2D photonic crystal are studied. Comprehensive ab initio
      numerical simulations based on the finite-difference time-domain method show
      efficient third-harmonic generation in a photonic crystal waveguide consisting of
      the 1D defect line. The relationship between the third harmonic generation
      process and the nonlinear modal properties of the waveguide is discussed. We
      investigate optical limiting in such a device, that is, control of the
      transmitted power as a function of the Kerr-induced variation of the refractive
      index. Power dependent spectral changes in such a device and its use as a
      frequency selector are also examined.

PMID- 12786295
TI  - Enhanced mobility of strongly localized modes in waveguide arrays by inversion of
      stability.
AB  - A model equation governing the amplitude of the electric field in an array of
      coupled optical waveguides embedded in a material with Kerr nonlinearities is
      derived and explored. The equation is an extended discrete nonlinear Schrodinger
      equation with intersite nonlinearities. Attention is turned towards localized
      solutions and investigations are made from the viewpoint of the theory of
      discrete breathers (DBs). Stability analysis reveals an inversion of stability
      between stationary one-site and symmetric or antisymmetric two-site solutions
      connected to bifurcations with a pair of asymmetric intermediate DBs. The
      stability inversion leads to the existence of high-intensity narrow mobile
      solutions, which can propagate essentially radiationless. The direction and
      transverse velocity of the mobile solutions can be controlled by appropriate
      perturbations. Such solutions may have an important application for multiport
      switching, allowing unambiguous selection of output channel. The derived equation
      also supports compact DBs, which in some sense yield the best possible solutions
      for switching purposes.

PMID- 12786294
TI  - Analytic explanation of spatial resolution related to bandwidth and detector
      aperture size in thermoacoustic or photoacoustic reconstruction.
AB  - An analytic explanation of the spatial resolution in thermoacoustic or
      photoacoustic reconstruction is presented. Three types of specific recording
      geometries, including spherical, planar, and cylindrical surface, as well as
      other general cases, are investigated. Analytic expressions of the point-spread
      functions (PSF's), as a function of the bandwidth of the measurement system and
      the finite size of the detector aperture, are derived based on rigorous
      reconstruction formulas. The analyses clearly reveal that the dependence of the
      PSF's on the bandwidth of all recording geometries shares the same space
      invariant expression while the dependence on the aperture size of the detector
      differs. The bandwidth affects both axial and lateral resolutions; in contrast,
      the detector aperture blurs the lateral resolution greatly but the axial
      resolution only slightly.

PMID- 12786296
TI  - Tunable refraction effects in two-dimensional photonic crystals utilizing liquid
      crystals.
AB  - Tunable refraction effects in two-dimensional photonic crystals utilizing liquid
      crystals are theoretically demonstrated. Due to liquid crystals with
      anisotropies, the incident light propagates in photonic crystals at refractive
      angles different from those in photonic crystals composed of isotropic materials.
      Moreover, refractive angles can be changed by rotating the directors of liquid
      crystals. Tunable refraction effects are also discussed for the light with two
      kinds of frequencies: one is a frequency at the edge of a band gap, and the other
      is a frequency a little far from the edge of a band gap.

PMID- 12786297
TI  - Stable spatiotemporal spinning solitons in a bimodal cubic-quintic medium.
AB  - We investigate the formation of stable spatiotemporal three-dimensional (3D)
      solitons ("light bullets") with internal vorticity ("spin") in a bimodal system
      described by coupled cubic-quintic nonlinear Schrodinger equations. Two relevant
      versions of the model, for the linear and circular polarizations, are considered.
      In the former case, an important ingredient of the model are four-wave-mixing
      terms, which give rise to a phase-sensitive nonlinear coupling between two
      polarization components. Thresholds for the formation of both spinning and
      nonspinning 3D solitons are found. Instability growth rates of perturbation
      eigenmodes with different azimuthal indices are calculated as functions of the
      solitons' propagation constant. As a result, stability domains in the model's
      parameter plane are identified for solitons with the values of the spins of their
      components s=0 and s=1, while all the solitons with s> or =2 are unstable. The
      solitons with s=1 are stable only if their energy exceeds a certain critical
      value, so that, in typical cases, the stability region occupies approximately 25%
      of their existence domain. Direct simulations of the full system produce results
      that are in perfect agreement with the linear-stability analysis: stable 3D
      spinning solitons readily self-trap from initial Gaussian pulses with embedded
      vorticity, and easily heal themselves if strong perturbations are imposed, while
      unstable spinning solitons quickly split into a set of separating zero-spin
      fragments whose number is exactly equal to the azimuthal index of the strongest
      unstable perturbation eigenmode.

PMID- 12786298
TI  - Nondiffracting waves in anisotropic media.
AB  - Recently the physics of ballistic phonon propagation in anisotropic crystals has
      been studied with new phonon-imaging methods. In this paper we consider
      nondiffracting waves that can propagate in anisotropic crystals and analyze their
      properties that emerge specifically due to the anisotropy. We further present a
      detailed generation and detection scheme for the experimental verification of the
      wave modes considered.

PMID- 12786299
TI  - Interaction of pulses in the nonlinear Schrodinger model.
AB  - The interaction of two rectangular pulses in the nonlinear Schrodinger model is
      studied by solving the appropriate Zakharov-Shabat system. It is shown that two
      real pulses may result in an appearance of moving solitons. Different limiting
      cases, such as a single pulse with a phase jump, a single chirped pulse, in-phase
      and out-of-phase pulses, and pulses with frequency separation, are analyzed. The
      thresholds of creation of new solitons and multisoliton states are found.

PMID- 12786300
TI  - Plasmon localization and local field distribution in metal-dielectric films.
AB  - An exact and very efficient numerical method for calculating the effective
      conductivity and local-field distributions in random R-L-C networks is developed.
      Using this method, the local-field properties of random metal-dielectric films
      are investigated in a wide spectral range and for a variety of metal
      concentrations p. It is shown that for metal concentrations close to the
      percolation threshold (p=p(c)) and frequencies close to the resonance, the local
      field intensity is characterized by a non-Gaussian, exponentially broad
      distribution. For low and high metal concentrations a scaling region is formed
      that is due to the increasing number of noninteracting dipoles. The local
      electric fields are studied in terms of characteristic length parameters. The
      roles of both localized and extended eigenmodes in Kirchhoff's Hamiltonian are
      investigated.

PMID- 12786301
TI  - Disappearances of uncoupled modes in two-dimensional photonic crystals due to
      anisotropies of liquid crystals.
AB  - We demonstrate disappearances of uncoupled modes in two-dimensional photonic
      crystals due to anisotropies of liquid crystals theoretically. Mirror symmetry
      disappears in wave vectors by rotating directors of liquid crystals, which
      results in disappearances of uncoupled modes that cannot be excited by external
      plane waves. This property may provide large tunabilities in two-dimensional
      photonic crystals utilizing liquid crystals.

PMID- 12786302
TI  - Propagation of partially coherent pulsed beams in the spatiotemporal domain.
AB  - A generalized model to describe the spatiotemporal partially coherent pulsed
      beams is presented. The corresponding propagation formula is derived by using the
      partially coherent light theory. Based on this formula, we obtain a nonstationary
      generalized ABCD law (which illustrates the transformation of optical beams or
      pulses passing through media) to describe the spatiotemporal behavior of
      partially coherent Gaussian pulsed beams. The physical meaning of such
      generalized pulsed beams is discussed. An example to illustrate the application
      of this law is given.

PMID- 12786303
TI  - Light scattering from a randomly occupied optical lattice. I. Born approximation.
AB  - A theoretical study of the scattering of light from a randomly occupied optical
      lattice of resonant atoms is presented to reveal both the characteristics of the
      lattice and the properties of light scattered from the lattice. In the first
      order Born approximation we discuss here, a number of interesting effects are
      established, including sideband Stokes scattering, a finite angular coherence of
      the scattered light, and spectral line narrowing. Specifically, the degree of
      angular coherence of the scattered light is calculated, and it is shown that such
      coherence is strongly influenced by the regularity and size of the underlying
      lattice structure. The previously observed phenomenon of the sideband spectral
      line narrowing is also explained in terms of the localization of atoms in the
      trapping potential wells. Important information about the lattice can thus be
      recovered by analyzing the scattered light in the Born approximation.

PMID- 12786304
TI  - Light scattering from a randomly occupied optical lattice. II. The multiple
      scattering problem.
AB  - In this paper, we study the problem of multiple scattering of light from a
      randomly occupied optical lattice, thereby extending the first-order Born
      analysis of the previous paper. A full multiple-scattering analysis is essential
      to a complete understanding of the nature of light propagation inside a medium.
      Our calculations show that the incident wave, when resonant with the atomic
      medium, is rapidly extinguished due to multiple scattering. The decay constant
      depends critically on the incident wavelength, the lattice constant, the average
      number density of atoms, and their polarizability. Both the Bragg scattering
      amplitudes and directions are modified as a result of multiple scattering.
      Because of the random site occupation of an otherwise regular lattice structure,
      a coherent enhancement of the scattering cross section is also predicted to occur
      along a discrete set of directions that are related to the strictly backward
      direction by reciprocal lattice vectors.

PMID- 12786305
TI  - Limit cycle induced by multiplicative noise in a system of coupled Brownian
      motors.
AB  - We study a model consisting of N nonlinear oscillators with global periodic
      coupling, and local multiplicative and additive noises. The model was shown to
      undergo a nonequilibrium phase transition towards a broken-symmetry phase
      exhibiting noise-induced "ratchet" behavior. A previous study [H. S. Wio, S.
      Mangioni, and R. Deza, Physica D 168-169, 184 (2002)] focused on the relationship
      between the character of the hysteresis loop, the number of "homogeneous" mean
      field solutions, and the shape of the stationary mean-field probability
      distribution function. Here, we show-as suggested by the absence of stable
      solutions when the load force is beyond a critical value-the existence of a limit
      cycle induced by both multiplicative noise and global periodic coupling.

PMID- 12786306
TI  - Alternative interpretation of the sign reversal of secondary Bjerknes force
      acting between two pulsating gas bubbles.
AB  - It is known that in a certain case, the secondary Bjerknes force (which is a
      radiation force acting between pulsating bubbles) changes, e.g., from attraction
      to repulsion, as the bubbles approach each other. In this paper, a theoretical
      discussion of this phenomenon for two spherical bubbles is described. The present
      theory based on analysis of the transition frequencies of interacting bubbles [M.
      Ida, Phys. Lett. A 297, 210 (2002)] provides an interpretation, different from
      previous ones (e.g., by Doinikov and Zavtrak [Phys. Fluids 7, 1923 (1995)]), of
      the phenomenon. It is shown, for example, that the reversal that occurs when one
      bubble is smaller and the other is larger than a resonance size is due to the
      second-highest transition frequency of the smaller bubble, which cannot be
      obtained using traditional natural-frequency analysis.

PMID- 12786307
TI  - Discrete vector solitons in two-dimensional nonlinear waveguide arrays:
      solutions, stability, and dynamics.
AB  - We identify and investigate bimodal (vector) solitons in models of square-lattice
      arrays of nonlinear optical waveguides. These vector self-localized states are,
      in fact, self-induced channels in a nonlinear photonic-crystal matrix. Such two
      dimensional discrete vector solitons are possible in waveguide arrays in which
      each element carries two light beams that are either orthogonally polarized or
      have different carrier wavelengths. Estimates of the physical parameters
      necessary to support such soliton solutions in waveguide arrays are given. Using
      Newton relaxation methods, we obtain stationary vector-soliton solutions, and
      examine their stability through the computation of linearized eigenvalues for
      small perturbations. Our results may also be applicable to other systems such as
      two-component Bose-Einstein condensates trapped in a two-dimensional optical
      lattice.

PMID- 12786308
TI  - Effects of polarization on laser holography for microstructure fabrication.
AB  - We perform a kind of computer stimulation on the multi-laser-beam interference.
      Using this method, we picture the interference patterns and describe the
      influence of the polarization of lights upon the clarity of the pattern. We find
      out the relations between the polarization states of the lights for the case of
      the best pattern and provide an optimal solution of the polarization on
      holographic lithography technology, and experiential formulas. This kind of
      analysis will improve the fabrication of submicrometer periodic structure
      efficiently.

PMID- 12786309
TI  - Cylinder gratings in conical incidence with applications to woodpile structures.
AB  - We use our previous formulation for cylinder gratings in conical incidence to
      discuss the photonic band gap properties of woodpile structures. We study
      scattering matrices and Bloch modes of the woodpile, and use these to investigate
      the dependence of the optical properties on the number of layers. We give data on
      reflectance, transmittance and absorptance of metallic woodpiles as a function of
      wavelength and number of layers, using both the measured optical constants of
      tungsten and using a perfect conductivity idealization to characterize the metal.
      For semi-infinite metallic woodpiles, we show that polarization of the incident
      field is important, highlighting the role played by surface effects as opposed to
      lattice effects.

PMID- 12786310
TI  - Oscillatory wave fronts in chains of coupled nonlinear oscillators.
AB  - Wave front pinning and propagation in damped chains of coupled oscillators are
      studied. There are two important thresholds for an applied constant stress F: for
      |F|<F(cd) (dynamic Peierls stress), wave fronts fail to propagate, for
      F(cd)<|F|<F(cs) stable static and moving wave fronts coexist, and for |F|>F(cs)
      (static Peierls stress) there are only stable moving wave fronts. For piecewise
      linear models, extending an exact method of Atkinson and Cabrera's to chains with
      damped dynamics corroborates this description. For smooth nonlinearities, an
      approximate analytical description is found by means of the active point theory.
      Generically for small or zero damping, stable wave front profiles are nonmonotone
      and become wavy (oscillatory) in one of their tails.

PMID- 12786311
TI  - Example of bianisotropic electromagnetic crystals: the spiral medium.
AB  - In this paper the electromagnetic properties of bianisotropic electromagnetic
      crystals are studied. The crystals are assumed to be rectangular lattices of
      perfectly conducting helicoidal spirals. The analytical theory of dispersion and
      plane-wave reflection refers to the case when the spiral step and the radius are
      small compared to the wavelengths in the host medium. The periods of the lattice
      can be arbitrary. Explicit closed-form expressions are derived for the effective
      material parameters of the medium in the low-frequency regime. The medium
      eigenmodes are elliptically polarized, and one of them propagates without
      interaction with the lattice. As to the other eigenmode, the lattice has strong
      spatial dispersion even at extremely low frequencies in the direction along the
      spiral axes. Numerical examples are given. An analogy between the spiral medium
      and the medium of loaded wires is indicated.

PMID- 12786312
TI  - Solution of the time-dependent diffusion equation for layered diffusive media by
      the eigenfunction method.
AB  - An exact solution of the time-dependent diffusion equation for the case of a two-
      and a three-layered finite diffusive medium is proposed. The method is based on
      the decomposition of the fluence rate in a series of eigenfunctions and upon the
      solution of the consequent transcendental equation for the eigenvalues obtained
      from the boundary conditions. Comparisons among the solution of the diffusion
      equation and the results of Monte Carlo simulations show the correctness of the
      proposed model.

PMID- 12786313
TI  - Twist defects in helical sonic structures.
AB  - We analyze theoretically both the acoustic wave propagation in periodic media
      made of anisotropic materials whose stiffness tensor is uniformly rotating along
      a given axis x(3) and the defect mode produced by twisting about x(3) one part of
      the helical structure with respect to the other. Within the Bragg band of the
      periodic structure, the twist defect gives rise to a resonant mode that is a
      superposition of two standing waves: one localized with exp(-gamma|x(3)|)
      dependence centered at the defect and the other extended over the whole sample.
      The ratio between the amplitudes of the localized and nonlocalized waves depends
      sharply on both the twist angle and the elastic anisotropy, and can assume huge
      values. The defect mode and the resonance frequency omega(0) are defined by fully
      analytical and very simple expressions. Finally, we discuss how around omega(0),
      a finite sample acts as a frequency filter for circularly polarized shear waves,
      whose bandwidth can be changed by many orders of magnitude by varying the sample
      thickness, the twist angle, or the elastic anisotropy.

PMID- 12786314
TI  - Localized-mode evolution in a curved planar waveguide with combined Dirichlet and
      Neumann boundary conditions.
AB  - We present a theoretical study of a planar waveguide with a uniformly curved
      section. Opposite sides of the channel satisfy different boundary conditions. It
      is shown that if the Dirichlet condition is applied to the inner side of the
      strip and the Neumann one to the outer wall, then properties of such a system in
      many respects resemble those with the Dirichlet requirements on both surfaces.
      Namely, in both cases a propagation threshold for the curved section is smaller
      than its counterpart for the straight channel. As a consequence, a localized mode
      exists with its energy below the propagation threshold of the straight waveguide.
      Analysis of such states is presented as a function of the bend parameters. For
      the transport in the fundamental mode an interaction of a quasibound level split
      off from the higher-lying threshold, with its degenerate continuum counterpart,
      causes a dip in the transmission. Such a resonance is characterized by a location
      of its zero minimum E(min) and the half width Gamma. Changing the bend angle and
      radius, one varies E(min) and Gamma. In particular, for some critical parameters
      of the bend it is possible to turn the half width to zero, i.e., to eliminate the
      dip in the transmission. This corresponds to the absence of the interaction
      between the split-off level and the continuum, and, consequently, to the
      formation of the true bound state in the continuum. Vortex structure of the
      currents flowing in the waveguide near the resonance is also shown to strongly
      resemble the analogous results for the Dirichlet case. It is pointed out that the
      properties of the waveguide with the Neumann inner condition and the Dirichlet
      outer one mimic the duct with the Neumann requirements on the two sides, since
      for both these cases the propagation threshold in the curved section is greater
      than in the straight channel.

PMID- 12786315
TI  - Transverse instability and its long-term development for solitary waves of the
      (2+1)-dimensional Boussinesq equation.
AB  - The stability properties of line solitary wave solutions of the (2+1)-dimensional
      Boussinesq equation with respect to transverse perturbations and their
      consequences are considered. A geometric condition arising from a multisymplectic
      formulation of this equation gives an explicit relation between the parameters
      for transverse instability when the transverse wave number is small. The Evans
      function is then computed explicitly, giving the eigenvalues for the transverse
      instability for all transverse wave numbers. To determine the nonlinear and long
      time implications of the transverse instability, numerical simulations are
      performed using pseudospectral discretization. The numerics confirm the analytic
      results, and in all cases studied, the transverse instability leads to collapse.

PMID- 12786316
TI  - Phase transition and landscape statistics of the number partitioning problem.
AB  - The phase transition in the number partitioning problem (NPP), i.e., the
      transition from a region in the space of control parameters in which almost all
      instances have many solutions to a region in which almost all instances have no
      solution, is investigated by examining the energy landscape of this classic
      optimization problem. This is achieved by coding the information about the
      minimum energy paths connecting pairs of minima into a tree structure, termed a
      barrier tree, the leaves and internal nodes of which represent, respectively, the
      minima and the lowest energy saddles connecting those minima. Here we apply
      several measures of shape (balance and symmetry) as well as of branch lengths
      (barrier heights) to the barrier trees that result from the landscape of the NPP,
      aiming at identifying traces of the easy-hard transition. We find that it is not
      possible to tell the easy regime from the hard one by visual inspection of the
      trees or by measuring the barrier heights. Only the difficulty measure, given by
      the maximum value of the ratio between the barrier height and the energy surplus
      of local minima, succeeded in detecting traces of the phase transition in the
      tree. In addition, we show that the barrier trees associated with the NPP are
      very similar to random trees, contrasting dramatically with trees associated with
      the p spin-glass and random energy models. We also examine critically a recent
      conjecture on the equivalence between the NPP and a truncated random energy
      model.

PMID- 12786317
TI  - Efficient scheme for numerical simulations of the spin-bath decoherence.
AB  - We demonstrate that the Chebyshev expansion method is a very efficient numerical
      tool for studying spin-bath decoherence of quantum systems. We consider two
      typical problems arising in studying decoherence of quantum systems consisting of
      a few coupled spins: (i) determining the pointer states of the system and (ii)
      determining the temporal decay of quantum oscillations. As our results
      demonstrate, for determining the pointer states, the Chebyshev-based scheme is at
      least a factor of 8 faster than existing algorithms based on the Suzuki-Trotter
      decomposition. For problems of the second type, the Chebyshev-based approach is 3
      4 times faster than the Suzuki-Trotter-based schemes. This conclusion holds
      qualitatively for a wide spectrum of systems, with different spin baths and
      different Hamiltonians.

PMID- 12786318
TI  - Pressure evolution lattice-Boltzmann-equation method for two-phase flow with
      phase change.
AB  - A lattice-Boltzmann-equation method for nonideal gases augmented by the pressure
      evolution equation is proposed to simulate isothermal two-phase fluid flow with
      phase change. The pressure evolution equation is derived by taking time
      derivative of the equation of state for nonideal gases. Unlike previous methods
      that use the equation of state to update pressure, the pressure field is evolved
      using the pressure evolution equation. The new approach has two advantages.
      First, it can avoid spurious pressure fluctuations at phase interfaces that
      develop owing to the pressure update by the equation of state, thus improving
      numerical stability of the method. Second, it permits compressibility of the
      fluid at phase interfaces when phase change occurs due to pressurization and
      depressurization. The proposed method is applied to simulate an isothermal phase
      change process. The numerical result is in excellent agreement with the
      analytical solution.

PMID- 12786319
TI  - Macrostate data clustering.
AB  - We develop an effective nonhierarchical data clustering method using an analogy
      to the dynamic coarse graining of a stochastic system. Analyzing the eigensystem
      of an interitem transition matrix identifies fuzzy clusters corresponding to the
      metastable macroscopic states (macrostates) of a diffusive system. A "minimum
      uncertainty criterion" determines the linear transformation from eigenvectors to
      cluster-defining window functions. Eigenspectrum gap and cluster certainty
      conditions identify the proper number of clusters. The physically motivated fuzzy
      representation and associated uncertainty analysis distinguishes macrostate
      clustering from spectral partitioning methods. Macrostate data clustering solves
      a variety of test cases that challenge other methods.

PMID- 12786320
TI  - Accuracy of the lattice Boltzmann method based on analytical solutions.
AB  - In this paper, a simple method is proposed to obtain steady analytical solutions
      for the lattice Boltzmann method. Based on such analytical results, it is
      demonstrated how the accuracy of the lattice Boltzmann method can depend on the
      relative orientation of the lattice and the flow field. It is also demonstrated
      that the method can be useful to obtain a general class of analytical solutions
      for the lattice Boltzmann method. Finally, a simple relation is given between the
      compressibility error and the velocity field.

PMID- 12786321
TI  - One-step finite-difference time-domain algorithm to solve the Maxwell equations.
AB  - We present a one-step algorithm to solve the time-dependent Maxwell equations for
      systems with spatially varying permittivity and permeability. We compare the
      results of this algorithm with those obtained from the Yee algorithm and from
      unconditionally stable algorithms. We demonstrate that for a range of
      applications the one-step algorithm may be orders of magnitude more efficient
      than multiple time-step, finite-difference time-domain algorithms. We discuss
      both the virtues and limitations of this one-step approach.

PMID- 12786322
TI  - Two-dimensional projections of a hypercube.
AB  - We present a method to project a hypercube of arbitrary dimension on the plane,
      in such a way as to preserve, as well as possible, the distribution of distances
      between vertices. The method relies on a Monte Carlo optimization procedure that
      minimizes the squared difference between distances in the plane and in the
      hypercube, appropriately weighted. The plane projections provide a convenient way
      of visualization for dynamical processes taking place on the hypercube.

PMID- 12786323
TI  - Global persistence exponent of the two-dimensional Blume-Capel model.
AB  - The global persistence exponent theta(g) is calculated for the two-dimensional
      Blume-Capel model following a quench to the critical point from both disordered
      states and such with small initial magnetizations. Estimates are obtained for the
      nonequilibrium critical dynamics on the critical line and at the tricritical
      point. Ising-like universality is observed along the critical line and a
      different value theta(g)=1.080(4) is found at the tricritical point.

PMID- 12786324
TI  - Harmonic oscillator with multiplicative noise: nonmonotonic dependence on the
      strength and the rate of dichotomous noise.
AB  - The output signal of a undamped linear oscillator with a random frequency subject
      to a periodic force shows nonmonotonic dependence on the strength and the rate of
      color noise (stochastic resonance). The effect is absent for white noise.

PMID- 12786325
TI  - Depinning transition at the upper critical dimension.
AB  - We study the effect of quenched random field disorder on a driven elastic
      interface close to the depinning transition at the upper critical dimension
      d(c)=4 using the functional renormalization group. We have found that the
      displacement correlation function behaves with distance x as (ln xLambda(0))(2/3)
      for large x. Slightly above the depinning transition the force-velocity
      characteristics are described by the equation v approximately f|ln f|(2/9), while
      the correlation length behaves as L(v) approximately f(-1/2)|ln f|(1/6), where
      f=F/F(c)-1 is the reduced driving force.

PMID- 12786326
TI  - Lattice glass model with no tendency to crystallize.
AB  - We study a lattice model with two-body interactions that reproduces in three
      dimensions many features of structural glasses, such as cage effect and vanishing
      diffusivity. While having a crystalline state at low temperatures, it does not
      crystallize when quenched, even at the slowest cooling rate used, which makes it
      suitable to study the glass transition. We study the model on the Bethe lattice
      as well, and find a scenario typical of p-spin models, as in the Biroli-Mezard
      model.

PMID- 12786327
TI  - Mechanism of growth reduction of the deceleration-phase ablative Rayleigh-Taylor
      instability.
AB  - The deceleration-phase (dp) ablative Rayleigh-Taylor instability (RTI) of
      igniting and nonigniting inertial fusion capsules is studied by high-resolution
      two-dimensional Lagrangian fluid simulations. It is found that growth reduction
      of the dp-RTI with respect to classical RTI results from the advection of
      perturbed fluid elements outside a thin unstable fluid layer. Within this layer,
      at fixed Lagrangian position, perturbations grow approximately classically.

PMID- 12786328
TI  - Nonlinear drift waves in electron-positron-ion plasmas.
AB  - It is suggested that low-frequency drift waves can play an important role in the
      dynamics of electron-positron plasmas comprising some concentration of ions. In
      the electromagnetic case the drift wave couples with the shear Alfven wave in an
      electron-positron-ion plasma. The drift wave frequency can be very low in such
      plasmas depending on the concentration and density scale lengths of the plasma
      components. In the nonlinear regime these waves can give rise to dipolar vortices
      in both electrostatic and electromagnetic limits. The velocity of the nonlinear
      structure turns out to be different compared to the case of an electron-ion
      plasma.

PMID- 12786329
TI  - Classical acoustic waves in damped media.
AB  - A Green function technique is employed to investigate the propagation of
      classical damped acoustic waves in complex media. The calculations are based on
      the linear response function approach, which is very convenient to deal with this
      kind of problem. Both the displacement and the gradient displacement Green
      functions are determined. All deformations in the media are supposed to be
      negligible, so the motions considered here are purely acoustic waves. The damping
      term gamma is included in a phenomenological way into the wave vector expression.
      By using the fluctuation-dissipation theorem, the power spectrum of the acoustic
      waves is also derived and has interesting properties, the most important of them
      being a possible relation with the analysis of seismic reflection data.

PMID- 12786330
TI  - Guided modes in negative-refractive-index waveguides.
AB  - We study linear guided waves propagating in a slab waveguide made up of a
      negative-refractive-index material, the so-called left-handed waveguide. We
      reveal that the guided waves in left-handed waveguides possess a number of
      peculiar properties such as the absence of the fundamental modes, mode double
      degeneracy, and sign-varying energy flux. In particular, we predict the guided
      waves with a dipole-vortex structure of their Poynting vector.

PMID- 12786331
TI  - Directional photon transfer between two wires.
AB  - The directional transfer of a single photon from one wire to another, leaving all
      other neighbor states unaffected, is of great importance. We present a simple
      coupling structure that makes such transfer possible, for any given photon
      wavelength and linewidth. We give closed-form expressions for the parameters
      necessary to build such a structure. An illustration of our analytic study is
      given for the directional transmission of a telecommunication signal between two
      lines.

PMID- 12786332
TI  - Comment on "Atomic spectral line-free parameter deconvolution procedure".
AB  - Recently Milosavljevic and Poparic [Phys. Rev. E 63, 036404 (2001)] proposed a
      method for the deconvolution of isolated asymmetric plasma broadened atomic
      (neutral) spectral lines. The authors claim that their method enables a complete
      plasma diagnostics by applying this deconvolution on a single experimental line
      profile. In the present Comment the proposed deconvolution procedure and its
      application are reexamined.

PMID- 12786334
TI  - Large-scale simulations of diffusion-limited n-species annihilation.
AB  - We present results from computer simulations for diffusion-limited n-species
      annihilation, A(i)+A(j)-->0 (i,j=1,2, em leader,n;i not equal j), on the line,
      for lattices comprising of up to 2(28) sites, and where the process proceeds to
      completion (no further reactions possible), involving up to 10(15) time steps.
      These enormous simulations are made possible by the renormalized reaction-cell
      method. Our results suggest that the concentration decay exponent for n species
      is alpha(n)=(n-1)/2n instead of (2n-3)/(4n-4), as previously believed, and are in
      agreement with recent theoretical arguments of Deloubriere et al. We also propose
      an expression for Delta, the correction-to-scaling exponent for the concentration
      decay, defined by c(t) approximately t(-alpha)(A+Bt-Delta).

PMID- 12786335
TI  - Weighted scale-free networks with stochastic weight assignments.
AB  - We propose a model of weighted scale-free networks incorporating a stochastic
      scheme for weight assignments to the links, taking into account both the
      popularity and fitness of a node. As the network grows, the weights of links are
      driven either by the connectivity with probability p or by the fitness with
      probability 1-p. Numerical results show that the total weight exhibits a power
      law distribution with an exponent sigma that depends on the probability p. The
      exponent sigma decreases continuously as p increases. For p=0, the scaling
      behavior is the same as that of the connectivity distribution. An analytical
      expression for the total weight is derived so as to explain the features observed
      in the numerical results. Numerical results are also presented for a generalized
      model with a fitness-dependent link formation mechanism.

PMID- 12786336
TI  - Coherent dynamics of an asymmetric particle in a vertically vibrating bed.
AB  - Coherent motion is found to emerge out of fluctuations in a vibrated asymmetric
      particle. Depending on the parameters, amplitude, and frequency of the box, the
      motion of the particle is classified into several phases. The transition between
      fluctuating motion and unidirectional motion occurs with constant acceleration in
      the low-frequency regime and constant amplitude in the high-frequency regime. We
      show through dimensional analysis that this behavior does not depend on the
      detailed geometry of the particle.

PMID- 12786337
TI  - Reexamination of the Branly effect.
AB  - The electrical resistance of a metallic granular packing has been recorded at
      room temperature. A nearby burster between which sparks are produced, induces a
      decrease in the resistance of the granular packing as described in the works of
      Branly. Our measurements emphasize that the decrease is continuous and the
      resistance variations behave like a stretched exponential law due to the creation
      of new electrical paths as in nucleation-growth soldering processes. This
      behavior has been identified to be a diffusionlike process.

PMID- 12786338
TI  - Continuous isotropic-nematic liquid crystalline transition of F-actin solutions.
AB  - The phase transition from the isotropic (I) to nematic (N) liquid crystalline
      suspension of F-actin of average length l> or =3 microm was studied by local
      measurements of optical birefringence and protein concentration. Both parameters
      were detected to be continuous in the transition region, suggesting that the I-N
      transition is higher than first order. Thus we report experimental evidence for a
      continuous I-N transition for a suspension of rodlike macromolecules. Our
      findings are consistent with a recent theory by Lammert, Rokhsar, and Toner
      [Phys. Rev. Lett. 70, 1650 (1993)], predicting that the I-N transition may become
      continuous due to suppression of disclinations.

PMID- 12786339
TI  - Surface phase transitions in free-standing films of nonchiral tilted hexatic
      liquid crystals.
AB  - Surface freezing transitions in free-standing films of achiral Schiff's-base
      liquid crystals 5O.6 and 7O.7 exhibiting tilted hexatic phases have been studied
      using optical textures. The evolution of textures with temperature in 5O.6 films
      is qualitatively similar to that reported earlier in the ferphenyl ester FTE1,
      suggesting the existence of the surface smectic-L phase, except that the stripe
      texture in 5O.6 consists of alternating light and dark stripes of unequal widths.
      No stripe texture is observed in 7O.7.

PMID- 12786340
TI  - Dynamical mechanism for the conversion of energy at a molecular scale.
AB  - We propose a dynamical mechanism of a molecular machine for energy conversion, by
      considering a simple model describing the dynamics of two components, the head
      and the chain. After injection of energy to the head region, the energy is stored
      at one part for some time, and is used step by step, allowing the head to move
      directionally along the chain, irrespective of the direction of the input, under
      a fluctuating environment. Our system can adjust the timing with which the head
      crosses the energy barrier by taking advantage of internal dynamics and the
      flexibility of components. Some suggestions are given for molecular machines.

PMID- 12786341
TI  - Survival probability of a diffusing particle in the presence of Poisson
      distributed mobile traps.
AB  - The problem of a diffusing particle moving among diffusing traps is analyzed in
      general space dimension d. We consider the case where the traps are initially
      randomly distributed in space, with uniform density rho, and derive upper and
      lower bounds for the probability Q(t) (averaged over all particle and trap
      trajectories) that the particle survives up to time t. We show that, for 1< or
      =d< or =2, the bounds converge asymptotically to give Q(t) approximately exp(
      lambda(d)t(d/2)) for 1< or =d<2, where lambda(d)=(2/pid)sin(pid/2)(4piD)(d/2)rho
      and D is the diffusion constant of the traps, and that Q(t) approximately exp(
      4pirhoDt/ln t) for d=2. For d>2 bounds can still be derived, but they no longer
      converge for large t. For 1< or =d< or =2, these asymptotic forms are independent
      of the diffusion constant of the particle. The results are compared with
      simulation results obtained using a new algorithm [V. Mehra and P. Grassberger,
      Phys. Rev. E 65, 050101 (2002)] which is described in detail. Deviations from the
      predicted asymptotic forms are found to be large even for very small values of
      Q(t), indicating slowly decaying corrections whose form is consistent with the
      bounds. We also present results in d=1 for the case where the trap densities on
      either side of the particle are different. For this case we can still obtain
      exact bounds but they no longer converge.

PMID- 12786342
TI  - Analytical solution of space probability distributions of particles in a one
      dimensional ring.
AB  - Spatial probability distributions of a few particles having nonidentical masses
      in one-dimensional space with both periodic and fixed boundary conditions are
      analytically computed in statistical equilibrium states, and explicit solutions
      of the probability distributions are obtained. Some nontrivial interesting
      features of the probability distributions are predicted and fully confirmed by
      numerical simulations. The realization of a microcanonical equilibrium state of
      the system is justified by the agreement between the theoretical predictions and
      numerical observations.

PMID- 12786343
TI  - Peak effect in a driven lattice gas model.
AB  - We study the peak effect (PE), i.e., a sharp peak observed in the critical
      current as a function of the particle density, discovered in transport properties
      of a driven lattice gas model. We show that the PE corresponds to a first-order
      phase transition found in the undriven system at equilibrium, which in turn gives
      rise to an "anomalous" second peak in magnetic hysteresis loops. We also explain
      the "history" dependent phenomena observed in the PE region by investigating the
      system characteristic time scales, which diverge at low T and have a broad
      maximum as a function of the external field around the PE. The model we consider
      can be related to a coarse grained description of vortex lines in superconductors
      and we discuss the relations of the PE described here and the one experimentally
      observed in these systems.

PMID- 12786344
TI  - Random-walk-based estimates of transport properties in small specimens of
      composite materials.
AB  - A method based on random walks is developed for estimating the dc conductance and
      similar transport properties in small specimens of composite materials. The
      method is valid over a much wider range of material structures than are
      asymptotic methods, and requires only that the internal structure of the material
      be known. The error in its estimates is limited primarily by CPU speed. It is
      found to work best for composites consisting of a bulk conducting phase and
      inclusions of lower conductivity.

PMID- 12786345
TI  - Influence of spatiotemporally correlated noise on structure formation in
      excitable media.
AB  - We discuss the influence of additive, spatiotemporally correlated (i.e., colored)
      noise on pattern formation in a two-dimensional network of excitable systems. The
      signature of spatiotemporal stochastic resonance (STSR) is analyzed using cross
      correlation and information theoretic measures. It is found that the STSR
      behavior is affected by both the spatial and temporal correlations of the noise
      due to an interplay with the length scales of the deterministic network.
      Increasing the spatiotemporal noise correlation shifts the occurrence of STSR to
      smaller values of the noise variance. Additionally, if the spatial correlation of
      the noise exceeds that of the network, the excitation patterns disappear in favor
      of cloudy structures, directly rendering the underlying spatial noise field.

PMID- 12786346
TI  - Electrokinetic flows in a microdomain.
AB  - The discrete kinetic approach and diffuse-reflection type boundary conditions are
      adopted to solve the transport problem for many charged particles flowing along a
      microslab (or channel of a wide constriction within a confined slender
      microdomain). The preliminary results show that there are selected orientations
      related to the nontrivial velocity-slip fields for a range of Knudsen numbers if
      there is a nonboundary-driven forcing along the streamwise direction. As the
      Knudsen number increases, the value of this selected orientation decreases and
      the cross-stream velocity profile becomes relatively flat. Our results
      qualitatively resemble those reported by Burgreen and Nakache or Paul et al.

PMID- 12786347
TI  - Molecular dynamics study of a bilayer electron gas: single particle properties.
AB  - The single-particle dynamical properties of a strongly coupled, classical,
      symmetric electronic bilayer system have been investigated by molecular dynamics
      simulation. Results for the velocity correlation function, the single-particle
      scattering function, and their respective Fourier transforms have been
      calculated, and their behavior, as a function of the interlayer separation d, has
      been analyzed. The single-particle scattering function in particular, shows
      dramatic effects when the bilayer attains a staggered square lattice structure.
      This occurs when the interlayer separation is around 0.8a (a is the Wigner-Seitz
      radius), where our previous study showed a marked decrease in the diffusion
      coefficient.

PMID- 12786348
TI  - Slow dynamics of a confined supercooled binary mixture: direct space analysis.
AB  - Dynamical properties of a Lennard-Jones binary mixture embedded in an off-lattice
      matrix of soft spheres are studied in the direct space upon supercooling by
      molecular dynamics simulations. On lowering the temperature, the smaller
      particles tend to avoid the soft sphere interfaces and correspondingly their
      mobility decreases below one of the larger particles. The system displays a
      dynamic behavior, consistent with the mode coupling predictions. A decrease in
      the mode coupling crossover temperature with respect to the bulk is found. We
      however find that the range of validity of the theory shrinks with respect to the
      bulk. This is due to the change in the smaller particle mobility and to a
      substantial enhancement of hopping processes well above the crossover temperature
      upon confinement.

PMID- 12786349
TI  - Free energies from integral equation theories: enforcing path independence.
AB  - A variational formalism is constructed for deriving the chemical potential and
      the Helmholtz free energy in various statistical-mechanical integral equation
      theories of fluids. Nonzero bridge functions extending the scope of the theories
      beyond the hypernetted chain approximation can be classified as to whether or not
      they imply path dependence of the free energy. Classes of bridge functions free
      of the path dependence problem are derived, based on which a route is devised
      toward direct computation of free energies from the simulation of a single state.

PMID- 12786350
TI  - Collective ionic dynamics in the liquid Na-Cs alloy: an ab initio molecular
      dynamics study.
AB  - We present results for several structural and dynamical properties of the liquid
      Na-Cs alloy. The study has been carried out by means of the orbital-free ab
      initio molecular dynamics method, combined with local ionic pseudopotentials
      constructed within the same framework. The results show good agreement with the
      available experimental data, reproducing the homocoordinating tendency exhibited
      by this alloy.

PMID- 12786351
TI  - Heat conduction in one-dimensional lattices with on-site potential.
AB  - The process of heat conduction in one-dimensional lattices with on-site potential
      is studied by means of numerical simulation. Using the discrete Frenkel
      Kontorova, phi(4), and sinh-Gordon models we demonstrate that contrary to
      previously expressed opinions the sole anharmonicity of the on-site potential is
      insufficient to ensure the normal heat conductivity in these systems. The
      character of the heat conduction is determined by the spectrum of nonlinear
      excitations peculiar for every given model and therefore depends on the concrete
      potential shape and the temperature of the lattice. The reason is that the
      peculiarities of the nonlinear excitations and their interactions prescribe the
      energy scattering mechanism in each model. For sine-Gordon and phi(4) models,
      phonons are scattered at a dynamical lattice of topological solitons; for sinh
      Gordon and for phi(4) in a different parameter regime the phonons are scattered
      at localized high-frequency breathers (in the case of phi(4) the scattering
      mechanism switches with the growth of the temperature).

PMID- 12786352
TI  - Method for determining the shear stress in cylindrical systems.
AB  - We develop a method for determining the elements of the pressure tensor at a
      radius r in a cylindrically symmetric system, analogous to the so-called "method
      of planes" used in planar systems [B. D. Todd, Denis J. Evans, and Peter J.
      Daivis, Phys. Rev. E 52, 1627 (1995)]. We demonstrate its application in
      determining the radial shear stress dependence during molecular dynamics
      simulations of the forced flow of methane in cylindrical silica mesopores. Such
      expressions are useful for the examination of constitutive relations in the
      context of transport in confined systems.

PMID- 12786353
TI  - Phase behavior and dynamics of fluids in mesoporous glasses.
AB  - Equilibrium and dynamical relaxation behavior of fluids confined in disordered
      mesoporous glasses such as Vycor are studied based on a lattice model using mean
      field theory and Monte Carlo simulations. Preferential attractive interactions
      between the solid surfaces and the fluid suppresses macroscopic phase separation,
      while making the relaxation rate increasingly slow. The free energy landscape
      characterized by the presence of the many metastable minima separated by finite
      barriers dominates both the static and dynamic behavior of fluids at low
      temperature. Our results provide additional insight into the nature of hysteresis
      in adsorption measurements of gases in porous glasses.

PMID- 12786354
TI  - nth-Nearest-neighbor distribution functions of an interacting fluid from the pair
      correlation function: a hierarchical approach.
AB  - The paper presents a general formalism for the nth-nearest-neighbor distribution
      (NND) of identical interacting particles in a fluid confined in a nu-dimensional
      space. The nth-NND functions, W(n,r) (for n=1,2,3, em leader) in a fluid are
      obtained hierarchically in terms of the pair correlation function and W(n-1,r)
      alone. The radial distribution function (RDF) profiles obtained from the
      molecular dynamics (MD) simulation of Lennard-Jones (LJ) fluid is used to
      illustrate the results. It is demonstrated that the collective structural
      information contained in the maxima and minima of the RDF profiles being resolved
      in terms of individual NND functions may provide more insights about the
      microscopic neighborhood structure around a reference particle in a fluid.
      Representative comparison between the results obtained from the formalism and the
      MD simulation data shows good agreement. Apart from the quantities such as nth
      NND functions and nth-nearest-neighbor distances, the average neighbor population
      number is defined. These quantities are evaluated for the LJ model system and
      interesting density dependence of the microscopic neighborhood shell structures
      are discussed in terms of them. The relevance of the NND functions in various
      phenomena is also pointed out.

PMID- 12786355
TI  - Phase behavior and structure of Janus fluids.
AB  - The equilibrium phase behavior of Janus fluids is examined based on a model
      potential for the interaction between their constituents. Janus fluids consist of
      axisymmetric particles possessing two different "faces," e.g., one hydrophobic
      and one hydrophilic surface, and the interaction depends on the relative
      orientation. Starting from a short range, isotropic potential we make an ansatz
      for an anisotropic model interaction potential. Two types of symmetries of the
      particles are considered. One leads to a polar phase. The Helmholtz free energy
      and the pressure are calculated by the help of an augmented van der Waals
      approximation. A qualitative phase diagram is obtained. The appearance of a polar
      phase and the corresponding transition temperature are examined adapting a Landau
      de Gennes expansion of the orientational part of the free energy. Monte Carlo
      simulations are performed and the results are compared with the ones obtained by
      the analytical description.

PMID- 12786356
TI  - Collision statistics of driven granular materials.
AB  - We present an experimental investigation of the statistical properties of
      spherical granular particles on an inclined plane that are excited by an
      oscillating side wall. The data is obtained by high-speed imaging and particle
      tracking techniques. We identify all particles in the system and link their
      positions to form trajectories over long times. Thus, we identify particle
      collisions to measure the effective coefficient of restitution and find a broad
      distribution of values for the same impact angles. We find that the energy
      inelasticity can take on values greater than one, which implies that the
      rotational degrees of freedom play an important role in energy transfer. We also
      measure the distance and the time between collision events in order to directly
      determine the distribution of path lengths and the free times. These
      distributions are shown to deviate from expected theoretical forms for elastic
      spheres, demonstrating the inherent clustering in this system. We describe the
      data with a two-parameter fitting function and use it to calculate the mean free
      path and collision time. We find that the ratio of these values is consistent
      with the average velocity. The velocity distributions are observed to be strongly
      non-Gaussian and do not demonstrate any apparent universal behavior. We report
      the scaling of the second moment, which corresponds to the granular temperature,
      and higher order moments as a function of distance from the driving wall.
      Additionally, we measure long-time correlation functions in both space and in the
      velocities to probe diffusion in a dissipative gas.

PMID- 12786357
TI  - Sand stirred by chaotic advection.
AB  - We study the spatial structure of a granular material, N particles subject to
      inelastic mutual collisions, when it is stirred by a bidimensional smooth chaotic
      flow. A simple dynamical model is introduced where four different time scales are
      explicitly considered: (i) the Stokes time, accounting for the inertia of the
      particles, (ii) the mean collision time among the grains, (iii) the typical time
      scale of the flow, and (iv) the inverse of the Lyapunov exponent of the chaotic
      flow, which gives a typical time for the separation of two initially close
      parcels of fluid. Depending on the relative values of these different times, a
      complex scenario appears for the long-time steady spatial distribution of
      particles, where clusters of particles may or may not appear.

PMID- 12786358
TI  - Confined granular packings: structure, stress, and forces.
AB  - The structure and stresses of static granular packs in cylindrical containers are
      studied by using large-scale discrete element molecular dynamics simulations in
      three dimensions. We generate packings by both pouring and sedimentation and
      examine how the final state depends on the method of construction. The vertical
      stress becomes depth independent for deep piles and we compare these stress depth
      profiles to the classical Janssen theory. The majority of the tangential forces
      for particle-wall contacts are found to be close to the Coulomb failure
      criterion, in agreement with the theory of Janssen, while particle-particle
      contacts in the bulk are far from the Coulomb criterion. In addition, we show
      that a linear hydrostaticlike region at the top of the packings unexplained by
      the Janssen theory arises because most of the particle-wall tangential forces in
      this region are far from the Coulomb yield criterion. The distributions of
      particle-particle and particle-wall contact forces P(f) exhibit exponential-like
      decay at large forces in agreement with previous studies.

PMID- 12786359
TI  - Self-organized criticality in a bead pile.
AB  - Self-organized criticality has been proposed to explain complex dynamical systems
      near their critical points. This experiment examined a monodisperse conical bead
      pile and how the distribution of avalanches is affected by the pattern of beads
      glued on a base, by the size or shape of the base, and by the height at which
      each bead was dropped onto the pile. By measuring the number of avalanches for a
      given size that occurred during the experiment, the resulting distribution could
      be compared to a power law description. When the beads were dropped from a small
      height, all data were consistent with a simple power law of exponent -1.5, which
      is the mean-field model value. The data showed that neither the bead pattern on
      the base nor the base size or shape significantly affected the power law
      behavior. However, when the bead is dropped from different heights, then the
      power law description breaks down and a power law times an exponential is more
      appropriate. We found a scaling relationship in the distribution of avalanches
      for different heights and relate the data to an energy dissipation model. We both
      confirm self-organized criticality and observe deviations from it.

PMID- 12786360
TI  - Power-law distribution of pressure fluctuations in multiphase flow.
AB  - Bubbling fluidized beds are granular systems, in which a deep layer of particles
      is set in motion by a vertical gas stream, with the excess gas rising as bubbles
      through the bed. We show that pressure fluctuations in such a system have non
      Gaussian statistics. The probability density function has a power-law drop-off
      and is very well represented by a Tsallis distribution. Its shape is explained
      through the folding of the Gaussian distribution of pressure fluctuations
      produced by a monodisperse set of bubbles, onto the actual distribution of bubble
      sizes in the bed, assuming that bubbles coalesce via a Smoluchowski-type
      aggregation process. Therefore, the Tsallis statistics arise as a result of
      bubble polydispersity, rather than system nonextensivity.

PMID- 12786361
TI  - Graft polymer solutions as sticky hard-sphere colloids.
AB  - We show that a solution of a graft (comb) polymer can exhibit an adhesive hard
      sphere pair potential. In the present paper, static and dynamic light scattering
      measurements on a comb polymer at low molecular weight are performed and the
      results discussed in the framework of the colloidal theory for adhesive spheres.
      Renormalization group calculations are directly compared with experimental data
      on the cooperative diffusion coefficient using the scaled concentration
      parameter.

PMID- 12786362
TI  - Pair correlations of a dilute charged colloidal fluid near a glass wall.
AB  - Using confocal microscopy we examine the static structure of low density, highly
      charged colloidal suspensions near a repulsive glass boundary. We find no sign of
      an interparticle attraction of the magnitude noted previously.

PMID- 12786363
TI  - Fractal radar scattering from soil.
AB  - A general technique is developed to retrieve the fractal dimension of self
      similar soils through microwave (radar) scattering. The technique is based on a
      mathematical model relating the fractal dimensions of the georadargram to that of
      the scattering structure. Clear and different fractal signatures have been
      observed over four geosystems (soils and sediments) compared in this work.

PMID- 12786364
TI  - Pair dynamics in a glass-forming binary mixture: simulations and theory.
AB  - We have carried out molecular dynamics simulations to understand the dynamics of
      a tagged pair of atoms in a strongly nonideal glass-forming binary Lennard-Jones
      mixture. Here atom B is smaller than atom A (sigma(BB)=0.88sigma(AA), where
      sigma(AA) is the molecular diameter of the A particles) and the AB interaction is
      stronger than that given by Lorentz-Berthelot mixing rule
      (epsilon(AB)=1.5epsilon(AA), where epsilon(AA) is the interaction energy strength
      between the A particles). The generalized time-dependent pair distribution
      function is calculated separately for the three pairs (AA, BB, and AB). The three
      pairs are found to behave differently. The relative diffusion constants are found
      to vary in the order D(BB)(R)>D(AB)(R)>D(AA)(R), with D(BB)(R) approximately
      2D(AA)(R), showing the importance of the hopping process (B hops much more than
      A). We introduce a non-Gaussian parameter [alpha(P)(2)(t)] to monitor the
      relative motion of a pair of atoms and evaluate it for all the three pairs with
      initial separations chosen to be at the first peak of the corresponding partial
      radial distribution functions. At intermediate times, significant deviation from
      the Gaussian behavior of the pair distribution functions is observed with
      different degrees for the three pairs. A simple mean-field (MF) model, proposed
      originally by Haan [Phys. Rev. A 20, 2516 (1979)] for one-component liquid, is
      applied to the case of a binary mixture and compared with the simulation results.
      While the MF model successfully describes the dynamics of the AA and AB pairs,
      the agreement for the BB pair is less satisfactory. This is attributed to the
      large scale anharmonic motions of the B particles in a weak effective potential.
      Dynamics of the next nearest neighbor pairs is also investigated.

PMID- 12786365
TI  - Surface and capillary transitions in an associating binary mixture model.
AB  - We investigate the phase diagram of a two-component associating fluid mixture in
      the presence of selectively adsorbing substrates. The mixture is characterized by
      a bulk phase diagram that displays peculiar features such as closed loops of
      immiscibility. The presence of the substrates may interfere with the physical
      mechanism involved in the appearance of these phase diagrams, leading to an
      enhanced tendency to phase separate below the lower critical solution point.
      Three different cases are considered: a planar solid surface in contact with a
      bulk fluid, while the other two represent two models of porous systems, namely, a
      slit and an array on infinitely long parallel cylinders. We confirm that surface
      transitions, as well as capillary transitions for a large surface area to volume
      ratio, are stabilized in the one-phase region. Applicability of our results to
      experiments reported in the literature is discussed.

PMID- 12786366
TI  - Phase separation of a polymer blend driven by oscillating particles.
AB  - We study the possible formation of ordered structures of a binary polymer blend
      by introducing mobile particles in a periodically oscillating driving field. The
      particles which have a preferential attraction to one of the immiscible phases,
      will significantly perturb the phase separation of the system and breakup the
      isotropy of the system, so that some interesting structures such as lamellar and
      cylinder phases are observed by appropriate selection of the simulation
      parameters. We examine in detail the dependence of formed morphology and domain
      size on the oscillating fields, the relative composition of mixtures, the
      diffusion coefficient, and quench depth, and then discuss how to realize stable
      and highly ordered structures.

PMID- 12786367
TI  - Influence of phase transition and photoisomerization on interfacial rheology.
AB  - This paper presents the shear responses and interfacial rheology of
      photosensitive monolayers. Langmuir films of a fatty acid containing an
      azobenzene moiety that can undergo trans-cis photoisomerization have been
      investigated for their structural and dynamical properties. The cis conformation
      produces a structureless, Newtonian film that cannot be oriented by surface
      flows. Transforming the molecule to the trans configuration produces a well
      packed film that responds to flow with an anisotropic and non-Newtonian
      character. The trans state supports two separate phases, a low-pressure phase
      where the azobenzene group is free to rotate, and a high-pressure phase where
      this moiety is frozen in place.

PMID- 12786368
TI  - Dynamics of atoms in a condensing cluster.
AB  - The dynamics of single particles in a cluster on condensation from the
      supersaturated vapor phase is studied by a kinetic approach. An insight into the
      distinctive flow field in the vicinity of a cluster is obtained for initial and
      late stage evolution. Inside the core the single atoms diffuse freely and the
      initial velocity decays rapidly with time. In the interfacial region between the
      cluster core and the vapor, the surface pressure produces a directed radial
      motion and a long time radial drift into the cluster core. Far from the cluster,
      the atoms move in the vapor state of low density and high diffusion constant. The
      mean square displacement and the velocity correlation lend support to the results
      and are compared with recent molecular dynamics simulations on a nucleating argon
      cluster.

PMID- 12786369
TI  - Theory of localized adsorption on surfaces undergoing reversible reconstruction.
AB  - A rate equation, which takes explicitly into account the surface reconstruction
      phenomena occurring (reversibly or irreversibly) while adsorption or desorption
      proceeds, is proposed. The equation contains a few free parameters which specify
      the adsorption and desorption rate constants, and the reconstruction and
      irreversibility degrees of the process. A complete qualitative study of the
      solutions of the rate equation for a case of reversible and self-similar
      reconstruction is given.

PMID- 12786370
TI  - Topological manifestations of surface-roughening collapse in Langmuir monolayers.
AB  - A transition from surface-roughening collapse to a random network collapse has
      been investigated in fatty acid Langmuir monolayers. In contrast to the random
      network crack pattern, the surface-roughening crack pattern grows on a much
      longer time scale and on a much shorter length scale. A change in the isotherm
      from a surface pressure "spike" to a "plateau" occurs at the transition. In the
      surface-roughening regime, the pattern is manifested by the emergence of a three
      dimensional (3D) disordered stripe phase with locally aligned, anisotropic stripe
      clusters. The individual stripes coalesce less with each other even at a late
      stage of the collapse process and there is a characteristic length for the stripe
      width and the nearest neighbor spacing. The pattern includes a high density of
      topological defects such as single open ends, twin open ends, branches, and
      loops. The effects of shear deformation on the observed patterns are discussed.

PMID- 12786371
TI  - Manipulation of anchoring strength in an azo-dye side chain polymer by
      photoisomerization.
AB  - The generation of surface anisotropy by photochemical means has been proposed as
      an attractive method to align liquid crystals. In this paper, we present an
      experimental study of the alignment induced on a liquid crystal by a polymer film
      containing azo-dye groups in the side chain. Optical measurements were performed
      in nematic liquid crystal cells to determine the azimuthal and zenithal anchoring
      strengths as a function of the irradiation energy and chromophores concentration.
      It was observed that the director tends to align perpendicular to the
      polarization direction of the incident light and the orientation process consists
      essentially of a rotation of the director in the plane parallel to the boundary
      surfaces. However, the concentration of azo-dye groups in the polymer film must
      exceed a minimum value to get a macroscopical effect on the liquid crystal
      alignment. It is shown that the azimuthal anchoring strength can be varied two
      orders of magnitude by controlling the irradiation energy and azo-dye
      concentration.

PMID- 12786372
TI  - Geometrical optics approach in liquid crystal films with three-dimensional
      director variations.
AB  - A formal geometrical optics approach (GOA) to the optics of nematic liquid
      crystals whose optic axis (director) varies in more than one dimension is
      described. The GOA is applied to the propagation of light through liquid crystal
      films whose director varies in three spatial dimensions. As an example, the GOA
      is applied to the calculation of light transmittance for the case of a liquid
      crystal cell which exhibits the homeotropic to multidomainlike transition (HMD
      cell). Properties of the GOA solution are explored, and comparison with the Jones
      calculus solution is also made. For variations on a smaller scale, where the
      Jones calculus breaks down, the GOA provides a fast, accurate method for
      calculating light transmittance. The results of light transmittance calculations
      for the HMD cell based on the director patterns provided by two methods, direct
      computer calculation and a previously developed simplified model, are in good
      agreement.

PMID- 12786373
TI  - Influence of shape and energy anisotropies on the phase diagram of discotic
      molecules.
AB  - We present Monte Carlo simulations of discotic molecules using the Gay-Berne
      potential with shape (kappa) and energy (kappa(')) anisotropies. Following the
      previous work of Bates and Luckhurst [J. Chem. Phys. 104, 6696 (1996)] at
      kappa=0.345, kappa(')=0.2 when we determine the sequence of different phases at
      the same reduced pressure P(*)=50, we find an additional phase at low
      temperatures corresponding to an orthorhombic crystalline phase and we
      characterize it. Keeping the shape anisotropy fixed at kappa=0.2, we determine
      the evolution of the phase diagram with varying energy anisotropy. At high
      kappa('), low anisotropy, the system is not able to build columns while at low
      kappa('), the system exhibits both orthorhombic crystal as well as hexagonal
      liquid crystal phases over a wide range of pressures and temperatures. The domain
      of stability of the nematic phase is found to systematically shift towards higher
      pressures as kappa(') decreases.

PMID- 12786374
TI  - Dielectric relaxation behavior of a liquid crystal showing an unusual type of
      antiferroelectric-ferroelectric-antiferroelectric phase sequence.
AB  - The temperature and frequency dependent dielectric relaxation behavior of a
      liquid crystalline (S)-(+)-1-methylheptyl 4-[2-(4-alkoxyphenyl) thiophene-5
      carbonylthiooxy] benzoate system is reported. Interesting successive
      antiferroelectric-ferroelectric-antiferroelectric (AF-FE-AF) phase transitions
      are observed in this system resembling the successive phase transitions observed
      in crystalline Rochelle salt. The smectic-C* (SmC*) to AF1 phase transition
      (around 103.0 degrees C) is first order in nature, predicted from the use of
      Orihara and Ishibashi theory. It is also found that a contribution of the
      ferroelectric SmC* phase ordering penetrates even in the antiferroelectric AF1
      (SmC(*)(A)) and AF2 (SmC(*)(A)) phases very close to the SmC*-AF1 and SmC*-AF2
      phase boundaries (critical regions). It is suggested that this type of mixing of
      AF and FE phases might cause surface induced ferroelectric- or ferroelectric-type
      ordering near the AF-FE phase transitions. A soft mode with Debye-type dispersion
      was observed in the SmA phase. The thermal behaviors of dielectric dispersion,
      absorption, and dielectric strength in different phases are also reported and
      discussed.

PMID- 12786375
TI  - Static and dynamic dielectric properties of strongly polar liquids in the
      vicinity of first order and weakly first order phase transitions.
AB  - The paper presents the results of measurements of the linear dielectric
      properties of the compounds from the homologous series of alkylcyanobiphenyls
      (C(n)H(2n+1)PhPhCN, nCB) in the vicinity of the first order transition (from the
      isotropic liquid to the crystalline phase) of nonmesogenic nCB's (n=2-4) and the
      weakly first order transition (from the isotropic liquid to the nematic phase) of
      5CB. The experimental method for the separation of the critical part of the
      static permittivity derivative and the activation energy for rotation of the
      mesogenic molecules, in the vicinity of weakly first order phase transition, is
      proposed. It is shown that the critical temperature dependence of the
      permittivity and the activation energy can be described with a function of (T
      T*)(-alpha) type, with the same values of the temperature of virtual transition
      of the second order (T*) and the critical exponent (alpha).

PMID- 12786376
TI  - Continuous nematic anchoring transition due to surface-induced smectic order.
AB  - A continuous transition from tilted to homeotropic alignment at an interface is
      observed at a temperature T(a) for a nematic liquid crystal on cooling toward the
      nematic-smectic-A phase transition temperature. T(a) is found to depend on the
      treatment of the substrate. The behavior is examined theoretically in terms of a
      pair of competing easy axes (homeotropic and planar) and the tilt elasticity
      associated with the growth of surface-induced smectic order.

PMID- 12786377
TI  - Transverse surface-induced polarization at the interface between a chiral nematic
      liquid crystal and a substrate.
AB  - A chiral nematic liquid crystal that is tilted by an angle theta(i) with respect
      to a substrate is subjected to an ac electric field at frequency omega applied
      parallel to the substrate. The nematic director is found to oscillate azimuthally
      about the normal to the liquid crystal-substrate interface at frequency omega,
      indicating that a nonzero polarization perpendicular to the molecular tilt plane
      exists at the interface. The interfacial polarization, anchoring strength
      coefficient, and bulk viscosity are obtained by measurements of the oscillation
      amplitude as a function of omega.

PMID- 12786378
TI  - Molecular dipoles and tilted smectic formation: a Monte Carlo study.
AB  - We investigate the possibility of forming a tilted smectic liquid crystal phase
      by suitably positioning two permanent dipoles in a rodlike molecule. We show,
      using Monte Carlo simulations, that a tilted smectic is formed from ellipsoidal
      Gay-Berne particles with two off-center outboard dipoles when these are directed
      along or at 60 degrees from the rod axis where they are located, but not when
      they are perpendicular to it. The properties of the phases obtained are studied
      in some detail.

PMID- 12786379
TI  - Anchoring behavior, orientational order, and reorientation dynamics of nematic
      liquid crystal droplets dispersed in cross-linked polymer networks.
AB  - The orientational ordering and the electro-optical properties of nematic liquid
      crystal (LC) droplets confined to cross-linked polymer networks are investigated
      as a function of the anchoring conditions at the polymer-liquid crystal
      interface. Normal alignment (homeotropic) or parallel alignment (planar) inside
      LC droplets was controlled by using acrylate polymers with appropriate side
      chains. Drastic changes in the reorientation dynamics of the confined nematic
      liquid crystal phase are observed, as well as in the orientational ordering of
      the phase-separated LC which was investigated by 13C-NMR (nuclear magnetic
      resonance) spectroscopy. The cross-link density of the polymer network also
      affects the orientational ordering and the electro-optical properties of the
      confined LC phase. Faster switching times and higher-order parameters were found
      for samples with LC droplets exhibiting planar anchoring.

PMID- 12786381
TI  - Compression-shear-induced tilt azimuthal orientation of amphiphilic monolayers at
      the air-water interface: a C(infinity)-->C2v transition in the flow of a two
      dimensional hexatic structure.
AB  - Compression-shear-induced tilt azimuthal orientation of amphiphilic monolayer in
      tilting phases (L2 and L'2) at the air-water interface is analyzed as dynamical
      equilibrium of the elastic distortion of orthogonally hexagonal structure of the
      molecules under compression-induced shear flow. It is shown theoretically that
      the compression can induce molecular tilts lying along and/or against the flow
      direction. All these tilts makeup the initial random tilt azimuth of the
      molecular tails along a uniform direction. At a threshold compression speed, it
      causes a C(infinity)-->C(2v)-symmetry transition at the air-water interface. With
      Maxwell displacement current and optical second-harmonic generation measurements,
      the above theoretical results are verified experimentally in a monolayer of 4
      heptyloxy-4(')-cyanobiphenyl.

PMID- 12786380
TI  - Interaction potentials for soft and hard ellipsoids.
AB  - Using results from colloid science we derive interaction potentials for computer
      simulations of mixtures of soft or hard ellipsoids of arbitrary shape and size.
      Our results are in many respects reminicent of potentials of the Gay-Berne type
      but have a well-defined microscopic interpretation and no adjustable parameters.
      Since our potentials require the calculation of similar variables, the
      modification of existing simulation codes for Gay-Berne potentials is
      straightforward. The computational performance should remain unaffected.

PMID- 12786382
TI  - Formation of a twisted synclinic structure by an antiferroelectric liquid crystal
      material with strong quadrupolar interlayer coupling.
AB  - Following the work of Rudquist et al. [J. Mater. Chem. 9, 1257 (1999)], the
      thresholdless mode exhibited by some devices filled with some antiferroelectric
      liquid crystal materials is widely accepted to be due to the formation of a
      twisted synclinic structure in the device. In this work, we consider under what
      circumstances this structure forms in preference to the expected anticlinic
      structure. We show that a strong polar interaction at the surfaces is a necessary
      but not sufficient condition, and that a strong quadrupolar component of the
      interlayer interaction is also required. Examination of the stability of the
      possible ground states reveals a simple explanation for the frequency and
      temperature dependent electro-optical properties that are observed
      experimentally, including priming.

PMID- 12786383
TI  - Optical measurement of azimuthal anchoring strength in nematic liquid crystals.
AB  - We have observed the azimuthal switching at the interface of nematic liquid
      crystals (LCs) and the aligning substrate, induced by the planar electric field
      of a fine comb electrode. Optical transmittance as a function of applied voltage
      was modeled by both the elastic theory with rigid anchoring and the Landau-de
      Gennes theory with the interfacial energy expression 1/2Wtr[(Q two down arrows -Q
      two down arrows (0))(2)], where Q two down arrows is the liquid crystal order
      parameter and Q two down arrows (0) is the surface order parameter induced by the
      aligning substrate. Optical data on the in-plane switching LC cells were found to
      differ qualitatively with the predictions of the rigid anchoring model but to
      agree well with those of the Landau-de Gennes theory. We obtain not only the
      strength W of the azimuthal anchoring, but also find the surface order parameter
      S(surface) to be 20-30 % less than that of the bulk. The optically measured
      azimuthal anchoring strength is in good agreement with the literature values
      determined through other means.

PMID- 12786384
TI  - Pressure-induced reduction of the Landau-Peierls instabilities in a side-chain
      polymer liquid crystal with reentrant polymorphism.
AB  - Cyanobiphenyl mesogens are known to exhibit partially bilayered smectic A (S(Ad))
      and also reentrant nematic (N(re)) phases. Nematic and smectic orders are coupled
      parameters which depend both on temperature and pressure. We report the first
      structural study of the influence of a hydrostatic pressure on the smectic phase.
      This study was carried out on a side-chain liquid crystalline polymer, by neutron
      diffraction using two specifically designed pressure cells. These results
      concluded first that the pressure acts on the phase elastic constants via a
      reduction of the layer fluctuations giving rise to a hardening of the phase
      together with an extension of the smectic domain towards higher temperatures.
      Second, the S(Ad)-N(re) phase transition temperature remains unchanged in the
      studied pressure range revealing that the polymer component plays an important
      role which allows us to subtract the associated packing interactions from the
      pressure-induced volume reduction.

PMID- 12786385
TI  - Fast Q-tensor method for modeling the dynamics of defects in a liquid crystal
      director field.
AB  - A fast Q-tensor method, which can model the defect dynamics in a liquid crystal
      director field, is presented. Conceptually based on the Oseen-Frank approach, we
      have added temperature energy density terms in addition to the strain energy
      terms, and an improved normalization method for fast calculations. The method is
      more compact and allows a larger time step than previous methods. The method is
      used to model the defect dynamics occurring during the topological state change
      from a splay to bend director field configuration.

PMID- 12786386
TI  - Structures and phase transitions in polar smectic liquid crystals.
AB  - A discrete phenomenological model of antiferroelectric liquid crystals is used to
      study the structures and phase transitions in bulk samples and thin films. An
      important ingredient of our investigations is minimization of the free energy
      with respect to the phase and modulus of the order parameter. A simple version of
      the free energy, which contains only the nearest-neighbor and the next-nearest
      neighbor layer interactions gives a complete phase diagram with all the observed
      smectic-C* (SmC*) variant phases. In thin free-standing films, surface ordering
      may lead to suppression of the bulk SmC(*)(alpha) helix and to formation of
      planar structures. Transitions between these structures are accompanied by the 90
      degrees reorientation of the polarization direction. We also discuss the
      influence of chirality on subphase structures.

PMID- 12786387
TI  - Nematic-liquid-crystal-air interface in a radial Hele-Shaw cell: electric field
      effects.
AB  - The influence of an external electric field (applied to the nematic liquid
      crystal layer) on the morphology of the nematic-liquid-crystal-air interface has
      been studied experimentally in radial Hele-Shaw geometry. The effective viscosity
      mu(eff) of the nematic has been tuned by the electric field E and by the flow. At
      low excess pressure p(e) (where the growth of the interface is controlled mainly
      by the surface tension sigma), the applied E has no significant influence on the
      morphology of the interface, but decreases its normal velocity due to the
      increase of mu(eff). At higher p(e) (where the growth is not only controlled by
      sigma, but also by the kinetic term that depends on the effective viscosity) a
      significant difference in the morphology has been observed as a function of E.
      Experiments have shown that the influence of the electric field on the pattern
      morphology increases with the driving force (pressure gradient).

PMID- 12786388
TI  - Influence of solvent quality on effective pair potentials between polymers in
      solution.
AB  - Solutions of interacting linear polymers are mapped onto a system of "soft"
      spherical particles interacting via an effective pair potential. This coarse
      graining reduces the individual monomer-level description to a problem involving
      only the center of mass (c.m.) of the polymer coils. The effective pair
      potentials are derived by inverting the c.m. pair distribution function,
      generated in Monte Carlo simulations, using the hypernetted chain closure. The
      method, previously devised for the self-avoiding walk model of polymers in good
      solvent, is extended to the case of polymers in solvents of variable quality by
      adding a finite nearest-neighbor monomer-monomer attraction to the previous model
      and varying the temperature. The resulting effective pair potential is found to
      depend strongly on temperature and polymer concentration. At low concentration
      the effective interaction becomes increasingly attractive as the temperature
      decreases, eventually violating thermodynamic stability criteria. However, as
      polymer concentration is increased at fixed temperature, the effective
      interaction reverts to mostly repulsive behavior. These issues help to illustrate
      some fundamental difficulties encountered when coarse-graining complex systems
      via effective pair potentials.

PMID- 12786389
TI  - Mechanical unfolding of directed polymers in a poor solvent: critical exponents.
AB  - We study the thermodynamics of an exactly solvable model of a self-interacting,
      partially directed self-avoiding walk in two dimensions when a force is applied
      on one end of the chain. The critical force for the unfolding is determined
      exactly, as a function of the temperature, below the Theta transition. The
      transition is of second order and is characterized by new critical exponents that
      are determined by a careful numerical analysis. The usual polymer critical index
      nu on the critical line, and another one which we call zeta, takes a nontrivial
      value that is numerically close to 2/3.

PMID- 12786390
TI  - Polyhedral vesicles: a Brownian dynamics simulation.
AB  - Polyhedral vesicles with a large bending modulus of the membrane, such as a gel
      phase lipid membrane, were studied using a Brownian dynamics simulation. The
      vesicles exhibited various polyhedral morphologies such as tetrahedron and cube
      shapes. We clarified two types of line defects on the edges of the polyhedrons:
      cracks of both monolayers at the spontaneous curvature of the monolayer C0<0, and
      a crack of the inner monolayer at C0> or =0. The inner monolayer curved
      positively around the latter defect. Our results suggest that the polyhedral
      morphology is controlled by C0.

PMID- 12786391
TI  - Optical characterization of glutamate dehydrogenase monolayers chemisorbed on
      SiO2.
AB  - This paper describes the formation of glutamate dehydrogenase monolayers on
      silicon dioxide, and their characterization by means of physical techniques,
      i.e., fluorescence spectroscopy and Fourier-transform infrared spectroscopy.
      Detailed investigations of the intrinsic stability of native proteins in solution
      were carried out to elucidate the occurrence of conformational changes induced by
      the immobilization procedure. The enzyme monolayers were deposited on SiO2 after
      preexposing silicon surfaces to 3-aminopropyltriethoxysilane and reacting the
      silylated surfaces with glutaric dialdehyde. The optical characterization
      demonstrates that the immobilization does not interfere with the fold pattern of
      the native enzyme. In addition, fluorescence spectroscopy, thermal denaturation,
      and quenching studies performed on the enzyme in solution well describe the
      folding and unfolding properties of glutamate dehydrogenase. The photophysical
      studies reported here are relevant for nanobioelectronics applications requiring
      protein immobilization on a chip.

PMID- 12786392
TI  - Dynamical mean-field theory of spiking neuron ensembles: response to a single
      spike with independent noises.
AB  - A semianalytical dynamical mean-field theory has been developed for a study of
      dynamics of an ensemble of N-unit FitzHugh-Nagumo neurons subject to white
      noises. Assuming weak noises and the Gaussian distribution of state variables, we
      have driven equations of motions for moments of local and global variables.
      Dynamical mean-field approximation (DMA) has replaced original, 2N-dimensional
      stochastic differential equations (DEs) by eight-dimensional deterministic DEs,
      whereas the conventional moment method yields N(2N+3)-dimensional deterministic
      DEs for local variables. We have discussed the dependence of the spike firing
      precision and the synchronization on the noise intensity, synaptic coupling, and
      the size of the neuron ensemble. The spike timing precision is shown to be
      improved by increasing the size of the neuron ensemble, even when there are no
      couplings among neurons. When the coupling is introduced, neurons in ensembles
      respond to an input spike with a partial synchronization. Results calculated by
      our DMA theory are in good agreement with those obtained by direct simulations.
      DMA theory is extended to a large cluster which can be divided into multiple
      subclusters according to their functions. A model calculation has demonstrated
      that when the noise intensity is moderate, the spike propagation with a fairly
      precise timing is possible among noisy subclusters with feed-forward couplings,
      as in the synfire chain. We have compared DMA theory with the conventional moment
      method, showing that the former may be alternatively derived from the latter by a
      reduction in the number of moments with the mean-field approximation.

PMID- 12786393
TI  - Activity dynamics in nonlocal interacting neural fields.
AB  - We study the activity of a synaptically coupled neuronal network consisting of an
      excitatory and an inhibitory layer with isotropic connections and nonlinear
      interactions. Using the mathematical model of Wilson and Cowan in two spatial
      dimensions, we first discuss a spatial hysteresis phenomenon. Then we analyze
      special traveling wave solutions with stationary shape. We establish existence
      conditions, derive analytic expressions of the particular solutions and their
      velocity, and finally present numerical simulations.

PMID- 12786394
TI  - Diffusion dynamics, moments, and distribution of first-passage time on the
      protein-folding energy landscape, with applications to single molecules.
AB  - We study the dynamics of protein folding via statistical energy-landscape theory.
      In particular, we concentrate on the local-connectivity case with the folding
      progress described by the fraction of native conformations. We found that the
      first passage-time (FPT) distribution undergoes a dynamic transition at a
      temperature below which the FPT distribution develops a power-law tail, a
      signature of the intermittent nonexponential kinetic phenomena for the folding
      dynamics. Possible applications to single-molecule dynamics experiments are
      discussed.

PMID- 12786395
TI  - Disappearance of spurious states in analog associative memories.
AB  - We show that symmetric n-mixture states, when they exist, are almost never stable
      in autoassociative networks with threshold-linear units. Only with a binary
      coding scheme, we could find a limited region of the parameter space in which
      either 2-mixture or 3-mixture states are stable attractors of the dynamics.

PMID- 12786396
TI  - Interactions between proteins bound to biomembranes.
AB  - We study a physical model for the interaction between general inclusions bound to
      fluid membranes that possess finite tension gamma, as well as the usual bending
      rigidity kappa. We are motivated by an interest in proteins bound to cell
      membranes that apply forces to these membranes, due to either entropic or direct
      chemical interactions. We find an exact analytic solution for the repulsive
      interaction between two similar circularly symmetric inclusions. This repulsion
      extends over length scales approximately sqrt[kappa/gamma] and contrasts with the
      membrane-mediated contact attraction for similar inclusions on tensionless
      membranes. For noncircularly symmetric inclusions we study the small,
      algebraically long-ranged, attractive contribution to the force that arises. We
      discuss the relevance of our results to biological phenomena, such as the budding
      of caveolae from cell membranes and the striations that are observed on their
      coats. These, and other, "gnarly buds" may prove fascinating to study further.

PMID- 12786397
TI  - Network landscape from a Brownian particle's perspective.
AB  - Given a complex biological or social network, how many clusters should it be
      decomposed into? We define the distance d(i,j) from node i to node j as the
      average number of steps a Brownian particle takes to reach j from i. Node j is a
      global attractor of i if d(i,j)< or =d(i,k) for any k of the graph; it is a local
      attractor of i if j in E(i) (the set of nearest neighbors of i) and d(i,j)< or
      =d(i,l) for any l in E(i). Based on the intuition that each node should have a
      high probability to be in the same community as its global (local) attractor on
      the global (local) scale, we present a simple method to uncover a network's
      community structure. This method is applied to several real networks and some
      discussion on its possible extensions is made.

PMID- 12786398
TI  - Universal behavior of localization of residue fluctuations in globular proteins.
AB  - Localization properties of residue fluctuations in globular proteins are studied
      theoretically by using a Gaussian network model. Participation ratio for each
      residue fluctuation mode is calculated. It is found that the relationship between
      participation ratio and frequency is similar for all globular proteins,
      indicating a universal behavior in spite of their different size, shape, and
      architecture.

PMID- 12786399
TI  - Dynamics of synaptically coupled integrate-and-fire-or-burst neurons.
AB  - The minimal integrate-and-fire-or-burst (IFB) neuron model reproduces the salient
      features of experimentally observed thalamocortical (TC) relay neuron response
      properties, including the temporal tuning of both tonic spiking (i.e.,
      conventional action potentials) and postinhibitory rebound bursting mediated by a
      low-threshold calcium current. In this paper we consider networks of IFB neurons
      with slow synaptic interactions and show how the dynamics may be described with a
      smooth firing-rate model. When the firing rate of the IFB model is dominated by a
      refractory process the equations of motion simplify and may be solved exactly.
      Numerical simulations are used to show that a pair of reciprocally interacting
      inhibitory spiking IFB TC neurons supports an alternating rhythm of the type
      predicted from the firing-rate theory. A change in a single parameter of the IFB
      neuron allows it to fire a burst of spikes in response to a depolarizing signal,
      so that it mimics the behavior of a reticular (RE) cell. Within a continuum model
      we show that a network of RE cells with on-center excitation can support a fast
      traveling pulse. In contrast, a network of inhibitory TC cells is found to
      support a slowly propagating lurching pulse.

PMID- 12786400
TI  - Dynamics of solitary blood waves in arteries with prostheses.
AB  - We analyze the behavior of blood waves interacting with a prosthesis following
      the Yomosa nonlinear wave theory extended to include the spatial variation of the
      arterial radius and wall rigidity. When the prosthesis is short or when its
      characteristics are close to those of the host artery, the amplitude of the blood
      solitary wave increases just proximal to the prosthesis and then decreases to a
      magnitude smaller than the normal value in a healthy vessel. In the presence of
      an extended prosthesis, we derive the reflection and transmission coefficients at
      the interfaces, and we thereby obtain the optimal characteristics for an ideal
      prosthesis. Our results agree qualitatively with known experimental and numerical
      studies.

PMID- 12786401
TI  - Dynamics of the evolution of learning algorithms by selection.
AB  - We study the evolution of artificial learning systems by means of selection.
      Genetic programming is used to generate populations of programs that implement
      algorithms used by neural network classifiers to learn a rule in a supervised
      learning scenario. In contrast to concentrating on final results, which would be
      the natural aim while designing good learning algorithms, we study the evolution
      process. Phenotypic and genotypic entropies, which describe the distribution of
      fitness and of symbols, respectively, are used to monitor the dynamics. We
      identify significant functional structures responsible for the improvements in
      the learning process. In particular, some combinations of variables and operators
      are useful in assessing performance in rule extraction and can thus implement
      annealing of the learning schedule. We also find combinations that can signal
      surprise, measured on a single example, by the difference between predicted and
      correct classification. When such favorable structures appear, they are
      disseminated on very short time scales throughout the population. Due to such
      abruptness they can be thought of as dynamical transitions. But foremost, we find
      a strict temporal order of such discoveries. Structures that measure performance
      are never useful before those for measuring surprise. Invasions of the population
      by such structures in the reverse order were never observed. Asymptotically, the
      generalization ability approaches Bayesian results.

PMID- 12786402
TI  - Simulation studies of polymer translocation through a channel.
AB  - Monte Carlo simulation studies of the translocation of homopolymers of length N
      driven through a channel have been performed. We find that the translocation time
      tau depends on temperature in a nontrivial way. For temperatures below some
      critical temperature theta(c), tau approximately T-1.4, whereas for T>theta(c),
      tau increases with temperature. The low temperature results are in good agreement
      with experimental findings as is the dependence of tau on the driving field
      strength. The velocity of translocation displays the same characteristics as
      found in experiment but the N dependence of tau shows the linear relationship
      observed in experiment only for large values of N. A possible reason for this is
      suggested.

PMID- 12786403
TI  - Defect coarsening in a biological system: the vascular cambium of cottonwood
      trees.
AB  - We present micrographic evidence for the annihilation of topological defect pairs
      and defect-mediated coarsening in the vascular cambium of cottonwood trees
      (Populus deltoides). We also show that a recently published mathematical model of
      cell orientation dynamics in the cambium reproduces many qualitative features of
      the defect coarsening process.

PMID- 12786404
TI  - Low-order chaos in sympathetic nerve activity and scaling of heartbeat intervals.
AB  - The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded
      heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious
      rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate
      that the dynamics of this system of three variables is low-order chaos, and that
      sympathetic nerve activity leads to heartbeat interval and blood pressure
      changes. It is suggested that impaired regulation of blood pressure by
      sympathetic nerve activity is likely to cause experimentally observable steeper
      scaling of heartbeat intervals in hypertensive (high blood pressure) rats.

PMID- 12786405
TI  - Nonlinear volatility of river flux fluctuations.
AB  - We study the spectral properties of the magnitudes of daily river flux
      increments, the volatility. The volatility series exhibits (i) strong seasonal
      periodicity and (ii) power-law correlations for time scales less than 1 yr. We
      test the nonlinear properties of the river flux increment series by randomizing
      its Fourier phases and find that the surrogate volatility series (i) has almost
      no seasonal periodicity and (ii) is weakly correlated for time scales less than 1
      yr. We quantify the degree of nonlinearity by measuring (i) the amplitude of the
      power spectrum at the seasonal peak and (ii) the correlation power-law exponent
      of the volatility series.

PMID- 12786406
TI  - Crossover between short- and long-time behavior of stress fluctuations and
      viscoelasticity of liquids.
AB  - An effective viscosity coefficient is introduced based on definite time averages
      of equilibrium stress fluctuations rather than stress correlations. Analysis of
      this quantity via molecular dynamics of a simple model liquid reveals a crossover
      between the expected short-time elastic and the long-time viscous behavior with
      increasing averaging time. The procedure allows us to extract the zero-rate shear
      viscosity when the averaging time becomes one order of magnitude larger than the
      relevant relaxation time. A relationship between this effective viscosity and the
      dynamic viscosities is established.

PMID- 12786407
TI  - Paramagnetic beads surfing on domain walls.
AB  - Paramagnetic beads electrostatically stabilized in aqueous solution are attracted
      toward domain walls in magnetic films. The position above the domain wall can be
      destabilized by realigning the beads magnetic moment with an external magnetic
      field. The destabilization may result in a steady state dissipative mode, where
      the beads surf on the slope of the moving domain wall. The technique could be an
      alternative route to probe electrostatic and hydrodynamic interactions between
      particles and interfaces, and could also serve as a model system for studying
      motion in a one-dimensional potential.

PMID- 12786408
TI  - Scaling exponent of the maximum growth probability in diffusion-limited
      aggregation.
AB  - An early (and influential) scaling relation in the multifractal theory of
      diffusion limited aggregation (DLA) is the Turkevich-Scher conjecture that
      relates the exponent alpha(min) that characterizes the "hottest" region of the
      harmonic measure and the fractal dimension D of the cluster, i.e.,
      D=1+alpha(min). Due to lack of accurate direct measurements of both D and
      alpha(min), this conjecture could never be put to a serious test. Using the
      method of iterated conformal maps, D was recently determined as D=1.713+/-0.003.
      In this paper, we determine alpha(min) accurately with the result
      alpha(min)=0.665+/-0.004. We thus conclude that the Turkevich-Scher conjecture is
      incorrect for DLA.

PMID- 12786409
TI  - Electrochemical reactions on catalyst particles with three-phase boundaries.
AB  - In fuel cells, electrochemical reactions are often assumed to occur on metal
      catalyst particles contacting simultaneously the ion-conducting electrolyte and
      gas phase. Our kinetic Monte Carlo simulations demonstrate that in this case the
      deviations from the Tafel law in the dependence of the reaction rate on the
      electrode potential may be related to diffusion of one of the adsorbed reactants
      along catalyst particles.

PMID- 12786410
TI  - Conformational transitions of a semiflexible polymer in nematic solvents.
AB  - Conformations of a single semiflexible polymer chain dissolved in a low-molecular
      weight liquid crystalline solvent (nematogen) are examined by using a mean field
      theory. We take into account a stiffness and partial orientational ordering of
      the polymer. As a result of an anisotropic coupling between the polymer and
      nematogen, we predict a discontinuous (or continuous) phase transition from a
      condensed-rodlike conformation to a swollen one of the polymer chain, depending
      on the stiffness of the polymer. We also discuss the effects of the nematic
      interaction between polymer segments.

PMID- 12786411
TI  - Induction of ferroelectricity in the B2 phase of a liquid crystal composed of
      achiral bent-core molecules.
AB  - We report the observation of a transition from the antiferroelectric B2 phase to
      a ferroelectric phase in a liquid crystal composed of achiral bent-core (banana
      shaped) molecules. The transition is induced by an electric field of magnitude
      larger than the switching threshold and is not reversible, i.e., the original B2
      phase does not reappear upon field removal. The transformation is accompanied by
      a dramatic texture change, resulting in an almost optically isotropic structure
      in the absence of field. The ferroelectric character assigned to the structure is
      based on the electro-optic behavior of the material and on previously reported
      dielectric measurements. A short-pitch smectic-C*-type structure is proposed for
      the ferroelectric phase.

PMID- 12786412
TI  - Global exponential stability of hybrid bidirectional associative memory neural
      networks with discrete delays.
AB  - In this paper, the dynamical characteristics of hybrid bidirectional associative
      memory neural networks with constant transmission delays are investigated.
      Without assuming symmetry of synaptic connection weights and monotonicity and
      differentiability of activation functions, Halanay-type inequalities (which are
      different from the approach of constructing Lyapunov functionals) are employed to
      derive the delay-independent sufficient conditions under which the networks
      converge exponentially to the equilibria associated with temporally uniform
      external inputs. Our results are less conservative and restrictive than
      previously known results.

PMID- 12786413
TI  - Comment on "Computation of the viscosity of a liquid from time averages of stress
      fluctuations".
AB  - In a recent paper, Hess and Evans [Phys. Rev. E 64, 011207 (2001)] propose a
      method different from the conventional Green-Kubo and Einstein methods to
      calculate viscosity in equilibrium molecular dynamics simulations. For a
      comparison, we calculate the shear viscosity of SPC/E water at 303 K using these
      three different methods. We find that the Hess-Evans method is not as good as the
      other two in practical application, especially for the fluids with high viscosity
      and complicated relaxation.

PMID- 12786414
TI  - Comment on "Structure of ferrofluid dynamics".
AB  - We compare known equations for ferrofluid magnetization with a recently proposed
      rectified Debye theory [H. W. Muller and M. Liu, Phys. Rev. E 64, 061405 (2001)]
      and demonstrate that the latter is unsatisfactory. Derived by a purely formal
      method, it contains numerous unknown parameters, fails to explain previous
      experiments, and has no heuristic force.

PMID- 12786416
TI  - Comment on "Signal-to-noise ratio gain in neuronal systems".
AB  - We discuss the gain in signal-to-noise ratio (SNR) recently reported by Liu et
      al. [Phys. Rev. E 63, 051912 (2001)] in the Hodgkin-Huxley neuronal model. We
      show first that the possibility of signal-to-noise ratio enhancements can be
      checked by consideration of the statistical characteristics of switching between
      the system states, and we examine how the SNR depends on the shape of a periodic
      signal. Second, we attempt to verify the SNR gain reported by Liu et al.: based
      on spectral calculations and analyses of switching statistics, we are unable to
      find any SNR gain in the Hodgkin-Huxley model.

PMID- 12786417
TI  - Global culture: a noise-induced transition in finite systems.
AB  - We analyze the effect of cultural drift, modeled as noise, in Axelrod's model for
      the dissemination of culture. The disordered multicultural frozen configurations
      are found not to be stable. This general result is proven rigorously in d=1,
      where the dynamics is described in terms of a Lyapunov potential. In d=2, the
      dynamics is governed by the average relaxation time T of perturbations. Noise at
      a rate r <or=T(-1) induces monocultural configurations, whereas r > or =T(-1)
      sustains disorder. In the thermodynamic limit, the relaxation time diverges and
      global polarization persists in spite of a dynamics of local convergence.

PMID- 12786418
TI  - Renormalization group for evolving networks.
AB  - We propose a renormalization group treatment of stochastically growing networks.
      As an example, we study percolation on growing scale-free networks in the
      framework of a real-space renormalization group approach. As a result, we find
      that the critical behavior of percolation on the growing networks differs from
      that in uncorrelated networks.

PMID- 12786419
TI  - Exact scaling properties of a hierarchical network model.
AB  - We report on the exact results for the degree K, the diameter D, the clustering
      coefficient C, and the betweenness centrality B of a hierarchical network model
      with a replication factor M. Such quantities are calculated exactly with the help
      of recursion relations. Using the results, we show that (i). the degree
      distribution follows a power law P(K) approximately K-gamma with gamma=1+ln
      M/ln(M-1), (ii). the diameter grows logarithmically as D approximately ln N with
      the number of nodes N, (iii). the clustering coefficient of each node is
      inversely proportional to its degree, C proportional, variant 1/K, and the
      average clustering coefficient is nonzero in the infinite N limit, and (iv). the
      betweenness centrality distribution follows a power law P(B) approximately B-2.
      We discuss a classification scheme of scale-free networks into the universality
      class with the clustering property and the betweenness centrality distribution.

PMID- 12786420
TI  - Pascal principle for diffusion-controlled trapping reactions.
AB  - In this paper, we analyze the long-time behavior of the survival probability
      P(A)(t) of an A particle, that performs lattice random walk in the presence of
      randomly moving traps B. We show that for both perfect and imperfect trapping
      reactions, for arbitrary spatial dimension d and for a rather general class of
      random walks, P(A)(t) is less than or equal to the survival probability of an
      immobile target A in the presence of randomly moving traps.

PMID- 12786421
TI  - Corner-transfer-matrix renormalization-group method for two-dimensional self
      avoiding walks and other O(n) models.
AB  - We present an extension of the corner-transfer-matrix renormalization-group
      (CTMRG) method to O(n) invariant models, with particular interest in the self
      avoiding walk class of models [O(n=0)]. The method is illustrated using an
      interacting self-avoiding walk model. Based on the efficiency and versatility,
      when compared to other available numerical methods, we present the CTMRG as the
      method of choice for two-dimensional self-avoiding walk problems.

PMID- 12786422
TI  - Pseudounitary symmetry and the Gaussian pseudounitary ensemble of random
      matrices.
AB  - Employing the currently discussed notion of pseudo-Hermiticity, we define a
      pseudounitary group. Further, we develop a random matrix theory that is invariant
      under such a group and call this ensemble of pseudo-Hermitian random matrices the
      pseudounitary ensemble. We obtain exact results for the nearest-neighbor level
      spacing distribution for (2 x 2) PT-invariant Hamiltonian matrices that have
      forms, approximately Sln(1/S) near zero spacing for three independent elements
      and approximately S for four independent elements. This shows a level repulsion
      in a marked distinction with an algebraic form S(beta) in the Wigner surmise. We
      believe that this paves the way for a description of varied phenomena in two
      dimensional statistical mechanics, quantum chromodynamics, and so on.

PMID- 12786423
TI  - Generalized phase synchronization in unidirectionally coupled chaotic
      oscillators.
AB  - We investigate phase synchronization between two identical or detuned response
      oscillators coupled to a slightly different drive oscillator. Our result is that
      phase synchronization can occur between response oscillators when they are driven
      by correlated (but not identical) inputs from the drive oscillator. We call this
      phenomenon generalized phase synchronization and clarify its characteristics
      using Lyapunov exponents and phase difference plots.

PMID- 12786424
TI  - Tracking fixed-point dynamics in an electrochemical system using delayed-feedback
      control.
AB  - We report numerical and experimental results indicating successful tracking of
      stabilized fixed points solutions in an electrochemical system. By applying a
      continuous delayed-feedback technique, periodic oscillations are suppressed via
      stabilization of a steady-state fixed point. Subsequently, using a simple
      continuation method involving an update term, this stabilized fixed point is
      tracked through the bifurcation diagram as a system parameter is slowly varied.
      Under the influence of this tracking protocol, inception of oscillatory dynamics
      is precluded over large parameter domains and through bifurcations.

PMID- 12786425
TI  - Universal scaling of Lyapunov exponents in coupled chaotic oscillators.
AB  - We have uncovered a phenomenon in coupled chaotic oscillators where a subset of
      Lyapunov exponents, which are originally zero in the absence of coupling, can
      become positive as the coupling is increased. This occurs for chaotic attractors
      having multiple scrolls, such as the Lorenz attractor. We argue that the
      phenomenon is due to the disturbance to the relative frequencies with which a
      trajectory visits different scrolls of the attractor. An algebraic scaling law is
      obtained which relates the Lyapunov exponents with the coupling strength. The
      scaling law appears to be universal.

PMID- 12786426
TI  - Nonequilibrium molecular dynamics simulations of a bubble.
AB  - Molecular dynamics simulations are performed to investigate the microscopic
      dynamics of a bubble when liquids are locally heated. We successfully observe
      that the heated atoms scatter the neighboring nonheated atoms and make a bubble,
      and then the bubble is cooled and compressed by the surrounding liquids. The
      bubble dynamics in this process agrees with the results of the Rayleigh-Plesset
      equation which describes the dynamics of a bubble in terms of macroscopic
      hydrodynamics. In this way, we clarify that the hydrodynamic description is
      reliable even for a microscopic bubble.

PMID- 12786427
TI  - Constraint on electromagnetic acceleration of highest energy cosmic rays.
AB  - The energetics of electromagnetic acceleration of ultrahigh-energy cosmic rays
      (UHECRs) is constrained both by confinement of a particle within an acceleration
      site and by radiative energy losses of the particle in the confining magnetic
      fields. We demonstrate that the detection of approximately 3 x 10(20) eV events
      is inconsistent with the hypothesis that compact cosmic accelerators with high
      magnetic fields can be the sources of UHECRs. This rules out the most popular
      candidates, namely spinning neutron stars, active galactic nuclei (AGNs). Galaxy
      clusters and, perhaps, AGN radio lobes and gamma-ray burst blast waves remain the
      only possible (although not very strong) candidates for UHECR acceleration sites.
      Our analysis places no limit on linear accelerators. With the data from the
      future Auger experiment one should be able to answer whether a conventional
      theory works or some new physics is required to explain the origin of UHECRs.

PMID- 12786428
TI  - Three-dimensional local density of states in a finite two-dimensional photonic
      crystal composed of cylinders.
AB  - The three-dimensional local density of states (LDOS), which determines the
      radiation dynamics of a point source, is presented here for a finite two
      dimensional photonic crystal as a function of space and frequency. The LDOS is
      obtained from the dyadic Green's function, which is calculated exactly using the
      multipole method. Maximum suppression in the LDOS occurs at the high frequency
      edge of the complete two-dimensional band gap and varies smoothly about this
      frequency. Macroporous silicon is shown to suppress the LDOS by one order of
      magnitude at the center of its air pores.

PMID- 12786429
TI  - Numerical method for a moving solid object in flows.
AB  - We propose a numerical method for dealing with a moving solid body that interacts
      with a complex liquid surface. The method is based on the level set method, the
      CIP method, and the ghost fluid method. The validity of the method was shown by
      applying it to Poiseuille and Couette flow problems. The method can precisely
      capture the boundary layer as well as a moving solid object.

PMID- 12786430
TI  - Optimal size of a complex network.
AB  - We investigate the response behavior of an Ising system, driven by an oscillating
      field, on a small-world network, with particular attention to the effects of the
      system size. The responses of the magnetization to the driving field are probed
      by means of Monte Carlo dynamic simulations with the varied rewiring probability.
      It is found that at low and high temperatures the occupancy ratio, measuring how
      many spins follow the driving field, behaves monotonically with the system size.
      At intermediate temperatures, on the other hand, the occupancy ratio first grows
      and then reduces as the size is increased, displaying a resonancelike peak at a
      finite value of the system size. In all cases, further increase of the size
      eventually leads to saturation to finite values; the size at which saturation
      emerges is observed to depend on the temperature, similarly to the correlation
      length of the system.

PMID- 12786431
TI  - Stationary and transient work-fluctuation theorems for a dragged Brownian
      particle.
AB  - Recently Wang et al. carried out a laboratory experiment, where a Brownian
      particle was dragged through a fluid by a harmonic force with constant velocity
      of its center. This experiment confirmed a theoretically predicted work related
      integrated transient fluctuation theorem (ITFT), which gives an expression for
      the ratio for the probability to find positive or negative values for the
      fluctuations of the total work done on the system in a given time in a transient
      state. The corresponding integrated stationary state fluctuation theorem (ISSFT)
      was not observed. Using an overdamped Langevin equation and an arbitrary motion
      for the center of the harmonic force, all quantities of interest for these
      theorems and the corresponding nonintegrated ones (TFT and SSFT, respectively)
      are theoretically explicitly obtained in this paper. While the TFT and the ITFT
      are satisfied for all times, the SSFT and the ISSFT only hold asymptotically in
      time. Suggestions for further experiments with arbitrary velocity of the harmonic
      force and in which also the ISSFT could be observed, are given. In addition, a
      nontrivial long-time relation between the ITFT and the ISSFT was discovered,
      which could be observed experimentally, especially in the case of a resonant
      circular motion of the center of the harmonic force.

PMID- 12786432
TI  - Surfaces of percolation systems in lattice problems.
AB  - The internal and external surface area of a percolation cluster along with a full
      surface area of whole percolation system are investigated both analytically and
      numerically. Numerical simulation is performed by a Monte Carlo method for site
      and bond problems on square and simple cubic lattices. It is shown that both the
      external and full surface areas of a percolation cluster as well as the full
      surface area of the whole percolation system have maxima for a certain share of
      occupied sites (for the site problem) or permeable bonds (for a bond problem). On
      the basis of a probabilistic approach, analytical expressions are obtained which
      relate the surface area of percolation cluster to its density. The last value has
      been studied in more details at present that allows to analyze the behavior of
      the above-mentioned surface for various lattices. Two particular technological
      processes are discussed where the surface area of a percolation cluster plays an
      important part: generation of electric current in a fuel cell and self
      propagating high-temperature synthesis in heterogeneous condensed systems.

PMID- 12786433
TI  - Critical statistics in quantum chaos and Calogero-Sutherland model at finite
      temperature.
AB  - We investigate the spectral properties of a generalized Gaussian orthogonal
      ensemble capable of describing critical statistics. The joint distribution of
      eigenvalues of this model is expressed as the diagonal element of the density
      matrix of a gas of particles governed by the Calogero-Sutherland (CS)
      Hamiltonian. Taking advantage of the correspondence between CS particles and
      eigenvalues, and utilizing a recently conjectured expression by Kravtsov and
      Tsvelik for the finite temperature density-density correlations of the CS model,
      we show that the number variance of our random matrix model is asymptotically
      linear with a slope depending on the parameters of the model. Such linear
      behavior is a signature of critical statistics. This random matrix model may be
      relevant for the description of spectral correlations of complex quantum systems
      with a self-similar or fractal Poincare section of its classical counterpart.
      This is shown in detail for two examples: the anisotropic Kepler problem and a
      kicked particle in a well potential. In both cases the number variance and the
      Delta(3) statistic are accurately described by our analytical results.

PMID- 12786434
TI  - Performance analysis of an irreversible quantum heat engine working with harmonic
      oscillators.
AB  - The cycle model of a regenerative quantum heat engine working with many
      noninteracting harmonic oscillators is established. The cycle consists of two
      isothermal and two constant-frequency processes. The performance of the cycle is
      investigated, based on the quantum master equation and semigroup approach. The
      inherent regenerative losses in the two constant-frequency processes are
      calculated. The expressions of several important performance parameters such as
      the efficiency, power output, and rate of the entropy production are derived for
      several interesting cases. Especially, the optimal performance of the cycle in
      high-temperature limit is discussed in detail. The maximum power output and the
      corresponding parameters are calculated. The optimal region of the efficiency and
      the optimal ranges of the temperatures of the working substance in the two
      isothermal processes are determined.

PMID- 12786435
TI  - Information geometry of the spherical model.
AB  - Motivated by the observation that geometrizing statistical mechanics offers an
      interesting alternative to more standard approaches, we calculate the scaling
      behavior of the curvature R of the information geometry metric for the spherical
      model. We find that R approximately epsilon(-2), where epsilon=beta(c)-beta is
      the distance from criticality. The discrepancy from the naively expected scaling
      R approximately epsilon(-3) is explained and compared with that for the Ising
      model on planar random graphs, which shares the same critical exponents.

PMID- 12786436
TI  - Generating correlated networks from uncorrelated ones.
AB  - Given an ensemble of random graphs with a specific degree distribution, we show
      that the transformation which converts these graphs to their line (edge-dual)
      graphs produces an ensemble of graphs with nearly the same degree distribution,
      but with degree correlations and a much higher clustering coefficient. We also
      study the percolation properties of these new graphs.

PMID- 12786437
TI  - Apparent phase transitions in finite one-dimensional sine-Gordon lattices.
AB  - We study the one-dimensional sine-Gordon model as a prototype of roughening
      phenomena. In spite of the fact that it has been recently proven that this model
      cannot have any phase transition [J. A. Cuesta and A. Sanchez, J. Phys. A 35,
      2373 (2002)], Langevin as well as Monte Carlo simulations strongly suggest the
      existence of a finite temperature separating a flat from a rough phase. We
      explain this result by means of the transfer operator formalism and show as a
      consequence that sine-Gordon lattices of any practically achievable size will
      exhibit this apparent phase transition at unexpectedly large temperatures.

PMID- 12786438
TI  - Localization properties of the anomalous diffusion phase in the directed trap
      model and in the Sinai diffusion with a bias.
AB  - We study the localization properties of the anomalous diffusion phase x
      approximately t(micro) with 0<micro<1, which exists both in the Sinai diffusion
      with a small bias, and in the related directed trap model presenting a broad
      distribution of trapping times p(tau) approximately 1/tau(1+micro). Our starting
      point is the real space renormalization method, in which the whole thermal packet
      is considered to be in the same renormalized valley at large time: this
      assumption is asymptotically exact only in the limit of vanishing bias micro-->0
      and corresponds to the Golosov localization. For finite micro we thus generalize
      the usual real space renormalization method to allow for the spreading of the
      thermal packet over many renormalized valleys. Our construction allows one to
      compute exact series expansions in micro for all observables: to compute
      observables at order micro (n), it is sufficient to consider in each sample a
      spreading of the thermal packet onto at most (1+n) traps. So our approach
      provides a description of the structure of the thermal packet sample by sample,
      and a full statistical characterization of the important traps at a given order
      in micro. For the directed trap model, we show explicitly up to order micro(2)
      how to recover the exact expressions for the diffusion front, the thermal width,
      and the localization parameter Y2. We then use our method to derive exact results
      for the localization parameters Y(k) for arbitrary k, the correlation function of
      two particles, and the generating function of thermal cumulants. We then explain
      how these results apply to the Sinai diffusion with bias by deriving the
      quantitative mapping between the large-scale renormalized descriptions of the two
      models. Finally we study the internal structure of the effective "traps" for the
      Sinai model via path-integral methods.

PMID- 12786439
TI  - Intrinsic noise-induced phase transitions: beyond the noise interpretation.
AB  - We discuss intrinsic noise effects in stochastic multiplicative-noise partial
      differential equations, which are qualitatively independent of the noise
      interpretation (Ito vs Stratonovich), in particular in the context of noise
      induced ordering phase transitions. We study a model which, contrary to all cases
      known so far, exhibits such ordering transitions when the noise is interpreted
      not only according to Stratonovich, but also to Ito. The main feature of this
      model is the absence of a linear instability at the transition point. The
      dynamical properties of the resulting noise-induced growth processes are studied
      and compared in the two interpretations and with a reference Ginzburg-Landau-type
      model. A detailed discussion of a different numerical algorithm valid for both
      interpretations is also presented.

PMID- 12786440
TI  - Topology and correlations in structured scale-free networks.
AB  - We study a recently introduced class of scale-free networks showing a high
      clustering coefficient and nontrivial connectivity correlations. We find that the
      connectivity probability distribution strongly depends on the fine details of the
      model. We solve exactly the case of low average connectivity, providing also
      exact expressions for the clustering and degree correlation functions. The model
      also exhibits a lack of small-world properties in the whole parameter range. We
      discuss the physical properties of these networks in the light of the present
      detailed analysis.

PMID- 12786441
TI  - Role of the interaction matrix in mean-field spin glass models.
AB  - Mean-field models of two-spin Ising spin glasses with interaction matrices taken
      from ensembles that are invariant under O(N) transformations are studied. A
      general study shows that the nature of the spin glass transition can be deduced
      from the eigenvalue spectrum of the interaction matrix. A simple replica approach
      is derived to carry out the average over the O(N) disorder. The analytic results
      are confirmed by the extensive Monte Carlo simulations for large system sizes and
      by the exact enumeration for small system sizes.

PMID- 12786442
TI  - Fluctuation cumulant behavior for the field-pulse-induced magnetization-reversal
      transition in Ising models.
AB  - The universality class of the dynamic magnetization-reversal transition, induced
      by a competing field pulse, in an Ising model on a square lattice, below its
      static ordering temperature, is studied here using Monte Carlo simulations.
      Fourth-order cumulant of the order parameter distribution is studied for
      different system sizes around the phase boundary region. The crossing point of
      the cumulant (for different system sizes) gives the transition point and the
      value of the cumulant at the transition point indicates the universality class of
      the transition. The cumulant value at the crossing point for low temperature and
      pulse width range is observed to be significantly less than that for the static
      transition in the same two-dimensional Ising model. The finite-size scaling
      behavior in this range also indicates a higher correlation length exponent value.
      For higher temperature and pulse width range, the transition seems to fall in a
      mean-field-like universality class.

PMID- 12786443
TI  - Crossover behavior in the event size distribution of the Olami-Feder-Christensen
      model.
AB  - The avalanche size distribution and supercritical toppling value distribution in
      the Olami-Feder-Christensen model are examined, demonstrating that there exists a
      crossover value alpha(X) approximately 0.14 for the conservation parameter in the
      model. We have further confirmed the location of this crossover by identifying
      upper and lower bounds for alpha(X). For levels of conservation below alpha(X)
      the asymptotic behavior, in the limit of both infinite-system-size and infinite
      precision arithmetic, consists only of avalanches of size 1 with all sites
      toppling exactly at the threshold value. For larger levels of conservation the
      probability of finding avalanches of size 2 or bigger remains nonzero in the
      asymptotic limit.

PMID- 12786444
TI  - Percolating granular superconductors.
AB  - We investigate diamagnetic fluctuations in percolating granular superconductors.
      Granular superconductors are known to have a rich phase diagram including normal,
      superconducting, and spin-glass phases. Focusing on the normal-superconducting
      and the normal-spin-glass transition at low temperatures, we study the
      diamagnetic susceptibility chi((1)) and the mean square fluctuations of the total
      magnetic moment chi((2)) of large clusters. Our work is based on a random
      Josephson network model that we analyze with the powerful methods of renormalized
      field theory. We investigate the structural properties of the Feynman diagrams
      contributing to the renormalization of chi((1)) and chi((2)). This allows us to
      determine the critical behavior of chi((1)) and chi((2)) to arbitrary order in
      perturbation theory.

PMID- 12786445
TI  - Phase diagram of symmetric binary mixtures at equimolar and nonequimolar
      concentrations: a systematic investigation.
AB  - We consider symmetric binary mixtures consisting of spherical particles with
      equal diameters interacting via a hard-core plus attractive tail potential with
      strengths epsilon(ij), i,j=1,2, such that epsilon(11)=epsilon(22)>epsilon(12).
      The phase diagram of the system at all densities and concentrations is
      investigated as a function of the unlike-to-like interaction ratio
      delta=epsilon(12)/epsilon(11) by means of the hierarchical reference theory. The
      results are related to those of previous investigations performed at equimolar
      concentration, as well as to the topology of the mean-field critical lines. As
      delta is increased in the interval 0<delta<1, we find first a regime where the
      phase diagram at equal species concentration displays a tricritical point, then
      one where both a tricritical and a liquid-vapor critical point are present. We
      did not find any clear evidence of the critical end point topology predicted by
      mean-field theory as delta approaches 1, at least up to delta=0.8, which is the
      largest value of delta investigated here. Particular attention was paid to the
      description of the critical-plus-tricritical point regime in the whole density
      concentration plane. In this situation, the phase diagram shows, in a certain
      temperature interval, a coexistence region that encloses an island of
      homogeneous, one-phase fluid.

PMID- 12786446
TI  - Anomaly of the height-height correlation functions in self-flattening surface
      growth.
AB  - By Monte Carlo simulations and scaling theories, we consider the height-height
      correlation function G(r,t;L) of the one-dimensional equilibrium self-flattening
      surface growths, where the deposition (evaporation) attempt only at the globally
      highest (lowest) site is suppressed. G(r,t:L) is shown to satisfy the anomalous
      scaling behavior G(r,t;L)=L(2alpha)g(1)(r/L(delta),t/L(z)) or
      G(r,t;L)=t(2beta)g(2)(r/t(1/z(')),L/t(1/z)). Here alpha, beta, and z are the
      roughness, growth, and dynamic exponents, respectively, for the surface width,
      with alpha=1/3 and z=alpha/beta=3/2. Anomalous exponents z(') and delta are found
      to satisfy z(')=9/4 and delta=z/z('). We also show that anomalous behavior of
      G(r,t;L) can be understood from a scaling theory based on the competition between
      local random-walk-like behavior and the global-length-scale suppression.

PMID- 12786447
TI  - Uncorrelated random networks.
AB  - We define a statistical ensemble of nondegenerate graphs, i.e., graphs without
      multiple-connections and self-connections between nodes. The node degree
      distribution is arbitrary, but the nodes are assumed to be uncorrelated. This
      completes our earlier publication [Phys. Rev. 64, 046118 (2001)] where trees and
      degenerate graphs were considered. An efficient algorithm generating
      nondegenerate graphs is constructed. The corresponding computer code is available
      on request. Finite-size effects in scale-free graphs, i.e., those where the tail
      of the degree distribution falls like n(-beta), are carefully studied. We find
      that in the absence of dynamical internode correlations the degree distribution
      is cut at a degree value scaling like N(gamma), with gamma=min[1/2,1/(beta-1)],
      where N is the total number of nodes. The consequence is that, independently of
      any specific model, the internode correlations seem to be a necessary ingredient
      of the physics of scale-free networks observed in nature.

PMID- 12786448
TI  - Percolation on two- and three-dimensional lattices.
AB  - In this work we apply a highly efficient Monte Carlo algorithm recently proposed
      by Newman and Ziff to treat percolation problems. The site and bond percolations
      are studied on a number of lattices in two and three dimensions. Quite good
      results for the wrapping probabilities, correlation length critical exponent, and
      critical concentration are obtained for the square, simple cubic, hexagonal close
      packed, and hexagonal lattices by using relatively small systems. We also confirm
      the universal aspect of the wrapping probabilities regarding site and bond
      dilution.

PMID- 12786449
TI  - Vortex patterns and infinite degeneracy in the uniformly frustrated XY models and
      lattice Coulomb gas.
AB  - We find analytically and numerically that there exist infinite degeneracies in
      the ground state vortex configurations of a uniformly frustrated XY model on a
      square lattice for cases of frustrations f=1/6, 1/7, 1/8, and 1/10. More
      generally, we could also obtain a class of exact solutions for the phase
      configurations corresponding to the cases of f=1/q=1/(2m) with an integer m>or=3
      of which the above cases of m=3, 4, and 5 correspond to the true ground states.
      These states are analogous to the staircase solutions originally given by Halsey
      [Phys. Rev. B 31, 5728 (1985)], which, however, are relevant in a different
      regime of the frustration parameter (or vortex density). In these quasistaircase
      states, all the gauge-invariant phase differences are found to be integer
      multiples of pi/2q. The supercurrents are conserved at each node in a trivial
      manner by separate channels. The infinite ground state degeneracy is preserved in
      the case of an arbitrary screening length for the corresponding lattice Coulomb
      gas.

PMID- 12786450
TI  - Evaluation of the improvement parameter in the lattice Hamiltonian approach to
      critical phenomena.
AB  - In lattice Hamiltonian systems with a quartic coupling gamma, a critical value
      gamma(*) may exist such that, when gamma=gamma(*), the leading irrelevant
      operator decouples from the Hamiltonian and the leading nonscaling contribution
      to renormalization-group invariant physical quantities (evaluated in the critical
      region) vanishes. The 1/N expansion technique is applied to the evaluation of
      gamma(*) for the lattice Hamiltonian of vector spin models with O(N) symmetry. As
      a byproduct, systematic asymptotic expansions for the relevant lattice massive
      one-loop integrals are obtained.

PMID- 12786451
TI  - Phase transition in fiber bundle models with recursive dynamics.
AB  - We study the phase transition in a class of fiber bundle models in which the
      fiber strengths are distributed randomly within a finite interval and global load
      sharing is assumed. The dynamics is expressed as recursion relations for the
      redistribution of the applied stress and the evolution of the surviving fraction
      of fibers. We show that an irreversible phase transition of second-order occurs,
      from a phase of partial failure to a phase of total failure, when the initial
      applied stress just exceeds a critical value. The phase transition is
      characterized by static and dynamic critical properties. We calculate exactly the
      critical value of the initial stress for three models of this kind, each with a
      different distribution of fiber strengths. We derive exact expressions for the
      order parameter, the susceptibility to changes in the initial applied stress, and
      the critical relaxation of the surviving fraction of fibers for all the three
      models. The static and dynamic critical exponents obtained from these expressions
      are found to be universal.

PMID- 12786452
TI  - Short-time critical dynamics of the Baxter-Wu model.
AB  - We study the early time behavior of the Baxter-Wu model, an Ising model with
      three-spin interactions on a triangular lattice. Our estimates for the dynamic
      exponent z are compatible with results recently obtained for two models which
      belong to the same universality class of the Baxter-Wu model: the two-dimensional
      four-state Potts model and the Ising model with three-spin interactions in one
      direction. However, our estimates for the dynamic exponent theta of the Baxter-Wu
      model are completely different from the values obtained for those models. This
      discrepancy could be related to the absence of a marginal operator in the Baxter
      Wu model.

PMID- 12786453
TI  - Failure due to fatigue in fiber bundles and solids.
AB  - We consider first a homogeneous fiber bundle model where all the fibers have got
      the same stress threshold (sigma(c)) beyond which all fail simultaneously in
      absence of noise. At finite noise, the bundle acquires a fatigue behavior due to
      the noise-induced failure probability at any stress sigma. We solve this dynamics
      of failure analytically and show that the average failure time tau of the bundle
      decreases exponentially as sigma-->sigma(c) from below and tau=0 for
      sigma>or=sigma(c). We also determine the avalanche size distribution during such
      failure and find a power law decay. We compare this fatigue behavior with that
      obtained phenomenologically for the nucleation of the Griffith cracks. Next we
      study numerically the fatigue behavior of random fiber bundles having simple
      distributions of individual fiber strengths, at stress sigma less than the
      bundle's strength sigma(c); (beyond which it fails instantly). The average
      failure time tau is again seen to decrease exponentially as sigma-->sigma(c);
      from below and the avalanche size distribution shows similar power law decay.
      These results are also in broad agreement with experimental observations on
      fatigue in solids. We believe, these observations regarding the failure time are
      useful for quantum breakdown phenomena in disordered systems.

PMID- 12786454
TI  - Transfer operator approach on three-dimensional quantum billiards with SO(2)
      symmetry.
AB  - This work demonstrates the application of Bogomolny's transfer operator method on
      three-dimensional dynamics. Motivated by experimental observations of lenslike
      metal clusters, the quantum billiards bounded by a flat bottom and an upper
      surface with SO(2) symmetry are studied. A precise determination of the energies
      with error less than 0.05% and exact predicted degeneracies in the special case
      of the half-sphere billiard confirm the efficiency of this method. Furthermore,
      the spectra and degeneracies of lens billiards with varying heights are
      explicitly determined.

PMID- 12786455
TI  - Direct scattering processes and signatures of chaos in quantum waveguides.
AB  - The effect of direct processes on the statistical properties of deterministic
      scattering processes in a chaotic waveguide is examined. The single-channel
      Poisson kernel describes well the distribution of S-matrix eigenphases when
      evaluated over an energy interval. When direct processes are transformed away,
      the scattering processes exhibit universal random matrix behavior. The effect of
      chaos on scattering wave functions, eigenphases, and time delays is discussed.

PMID- 12786456
TI  - Chaotic diffusion on periodic orbits: the perturbed Arnold cat map.
AB  - Chaotic diffusion on periodic orbits (POs) is studied for the perturbed Arnold
      cat map on a cylinder, in a range of perturbation parameters corresponding to an
      extended structural-stability regime of the system on the torus. The diffusion
      coefficient is calculated, using the following PO formulas: (1). the curvature
      expansion of the Ruelle zeta function; (2). the average of the PO winding-number
      squared, w(2), weighted by a stability factor; (3). the uniform (nonweighted)
      average of w(2). The results from formulas (1). and (2). agree very well with
      those obtained by standard methods, for all the perturbation parameters
      considered. Formula (3). gives reasonably accurate results for sufficiently small
      parameters corresponding also to cases of a considerably nonuniform
      hyperbolicity. This is due to uniformity sum rules satisfied by the PO Lyapunov
      eigenvalues at fixed w. These sum rules follow from general arguments and are
      supported by much numerical evidence.

PMID- 12786457
TI  - Indications of nonlinear structures in brain electrical activity.
AB  - The dynamical properties of electroencephalogram (EEG) segments have recently
      been analyzed by Andrzejak and co-workers for different recording regions and for
      different brain states, using the nonlinear prediction error and an estimate of
      the correlation dimension. In this paper, we further investigate the nonlinear
      properties of the EEG signals using two established nonlinear analysis methods,
      and introduce a "delay vector variance" (DVV) method for better characterizing a
      time series. The proposed DVV method is shown to enable a comprehensive
      characterization of the time series, allowing for a much improved classification
      of signal modes. This way, the analysis of Andrzejak and co-workers can be
      extended toward classification of different brain states. The obtained results
      comply with those described by Andrzejak et al., and provide complementary
      indications of nonlinearity in the signals.

PMID- 12786458
TI  - Transitions from spatiotemporal chaos to cluster and complete synchronization
      states in a shift-invariant set of coupled nonlinear oscillators.
AB  - We study the spatiotemporal dynamics of a ring of diffusely coupled single-well
      Duffing oscillators. The transitions from spatiotemporal chaos to cluster and
      complete synchronization states are particularly investigated, as well as the
      Hopf bifurcations to instability. It is found that the underlying mechanism of
      these transitions relies on the motion of the representative points corresponding
      to the system's nondegenerated spatial transverse Fourier modes in the parametric
      Strutt diagram. A scaling law is used to demonstrate that the compact interval of
      the scalar coupling parameter values leading to cluster synchronization broadens
      in a square-power-like fashion as the number of oscillators is increased. The
      analytical approach is confirmed by numerical simulations.

PMID- 12786459
TI  - Front propagation and diffusion in the A left arrow over right arrow A+A hard
      core reaction on a chain.
AB  - We study front propagation and diffusion in the reaction-diffusion system A left
      arrow over right arrow A+A on a lattice. On each lattice site at most one A
      particle is allowed at any time. In this paper, we analyze the problem in the
      full range of parameter space, keeping the discrete nature of the lattice and the
      particles intact. Our analysis of the stochastic dynamics of the foremost
      occupied lattice site yields simple expressions for the front speed and the front
      diffusion coefficient which are in excellent agreement with simulation results.

PMID- 12786460
TI  - Influence of solitons on the transition to spatiotemporal chaos in coupled map
      lattices.
AB  - We study the transition from laminar to chaotic behavior in deterministic chaotic
      coupled map lattices and in an extension of the stochastic Domany-Kinzel cellular
      automaton [E. Domany and W. Kinzel, Phys. Rev. Lett. 53, 311 (1984)]. For the
      deterministic coupled map lattices, we find evidence that "solitons" can change
      the nature of the transition: for short soliton lifetimes it is of second order,
      while for longer but finite lifetimes, it is more reminiscent of a first-order
      transition. In the second-order regime, the deterministic model behaves like
      directed percolation with infinitely many absorbing states; we present evidence
      obtained from the study of bulk properties and the spreading of chaotic seeds in
      a laminar background. To study the influence of the solitons more specifically,
      we introduce a soliton including variant of the stochastic Domany-Kinzel cellular
      automaton. Similar to the deterministic model, we find a transition from second-
      to first-order behavior due to the solitons, both in a mean-field analysis and in
      a numerical study of the statistical properties of this stochastic model. Our
      study illustrates that under the appropriate mapping some deterministic chaotic
      systems behave like stochastic models; but it is hard to know precisely which
      degrees of freedom need to be included in such description.

PMID- 12786461
TI  - Low-frequency switching in a transistor amplifier.
AB  - It is known from extensive work with the diode resonator that the nonlinear
      properties of a P-N junction can lead to period doubling, chaos, and other
      complicated behaviors in a driven circuit. There has been very little work on
      what happens when more than one P-N junction is present. In this work, the first
      step towards multiple P-N junction circuits is taken by doing both experiments
      and simulations with a single-transistor amplifier using a bipolar transistor.
      Period doubling and chaos are seen when the amplifier is driven with signals
      between 100 kHz and 1 MHz, and they coincide with a very low frequency switching
      between different period doubled (or chaotic) wave forms. The switching
      frequencies are between 5 and 10 Hz. The switching behavior was confirmed in a
      simplified model of the transistor amplifier.

PMID- 12786462
TI  - Can simple renormalization theories describe the trapping of chaotic trajectories
      in mixed systems?
AB  - We investigate the relation between the chaotic dynamics and the hierarchical
      phase-space structure of the standard map as an example for generic Hamiltonian
      systems with a mixed phase space. We demonstrate that even in ideal situations
      when the phase-space structure is dominated by a single scaling, the long-time
      dynamics is not dominated by this scaling. This has consequences for the power
      law decay of correlations and Poincare recurrences.

PMID- 12786463
TI  - Semiclassical quantization of separatrix maps.
AB  - Quantization of energy balance equations, which describe a separatrixlike motion
      is presented. The method is based on an exact canonical transformation of the
      energy-time pair to the action-angle canonical pair, (E,t)-->(I,theta). Quantum
      mechanical dynamics can be studied in the framework of the new Hamiltonian. This
      transformation also establishes a relation between a wide class of the energy
      balance equations and dynamical localization of classical diffusion by quantum
      interference, that was studied in the field of quantum chaos. An exact solution
      for a simple system is presented as well.

PMID- 12786464
TI  - Transitions across a barrier induced by deterministic forcings.
AB  - The response of a bistable dynamical system to a deterministic forcing is studied
      with emphasis on the kinetics of the passage across the barrier separating the
      two states, and compared to classical Kramers' theory describing the response to
      a Gaussian white noise forcing. The existence of nontrivial thresholds for the
      occurrence of transitions is established. Analytic results complemented by
      numerical simulations are derived for the characteristics of these transitions
      for periodic and chaotic forcings. The probabilistic properties of the response
      are finally addressed and some connections are established with the universal
      stable distributions of probability theory.

PMID- 12786465
TI  - Chaotic transport of particles in two-dimensional periodic potentials driven by
      ac forces.
AB  - The diffusive and directed transport of particles in a two-dimensional periodic
      potential subjected to frictional and time-periodic forces is analyzed in detail.
      The model represents diffusion of atoms adsorbed on metal surfaces under an
      applied ac electric field (surface electromigration) in the low-temperature
      limit. The second dimension and the potential energy coupling are shown to play
      an important role on both diffusion and net currents, depending on the direction
      of the drive. A properly chosen biharmonic field is able to control the directed
      ratchetlike dynamics of atoms on symmetric surfaces, since current reversals take
      place by different stabilization of attractors. Reversals identified with
      hysteresis loops between periodic running attractors are robust against an
      increase of the second harmonic amplitude, and against temperature effects inside
      the experimental range for measurements of surface diffusion.

PMID- 12786466
TI  - Nonlinear dynamics of a semiconductor laser with filtered optical feedback and
      the influence of noise.
AB  - We investigate the influence of quantum noise on the highly complex nonlinear
      dynamics that arise in a single-mode semiconductor laser subject to filtered
      optical feedback. Our numerical study, which utilizes rate equations that are
      augmented by Langevin noise terms to account for the spontaneous-recombination
      noise, shows that for relatively broad filters the noise may lead to
      qualitatively different dynamics than predicted by a deterministic analysis. In
      particular, we find that certain attractors that are predicted in the absence of
      noise may no longer be available when the effects of noise are correctly
      incorporated. For narrow bandwidth filters we demonstrate optical-injection-like
      behavior and identify locking of the semiconductor laser to the relaxation
      oscillation side peaks. In general, the results indicate that shot noise in the
      laser can influence the dynamics quite substantially.

PMID- 12786467
TI  - Dynamics of many-particle fragmentation in a cellular automaton model.
AB  - A three-dimensional cellular automaton model developed by the authors to deal
      with the dynamics of N-body interactions has been adapted to investigate the head
      on collision of two identical bound clusters of particles, and the ensuing
      process of fragmentation. The range of impact energies is chosen low enough, to
      secure that a compound bound cluster can be formed. The model is devised to
      simulate the laboratory set-up of fragmentation experiments as monitored by 4 pi
      detectors. The particles interact via a Lennard-Jones potential. At low impact
      energies the numerical experiments following the dynamics of the individual
      particles indicate a phase of energy sharing among all the particles of the
      compound cluster. Fragments of all sizes are then found to evaporate from the
      latter cluster. The cluster sizes, measured in our setup by simulated 4 pi
      detectors, conform to a power law of exponent approximately 2.6. In an attempt to
      duplicate the laboratory caloric curves related, in particular, to nuclear
      fragmentation processes, we introduce several temperature parameters (kinetic
      temperature of nucleons, kinetic temperature of fragments, reaction equilibrium
      temperatures). Theoretical caloric curves are then constructed for those
      temperature parameters, we regard as physically most relevant. Our results show
      that different temperature definitions generate different curve patterns,
      indicating that the fragmentation system remains far from thermodynamic
      equilibrium. The pattern of the laboratory caloric curve for Au-Au collision
      experiments as derived from a recent analysis [NuPECC Report, 1997 (unpublished)]
      is reproduced qualitatively by our reaction temperatures.

PMID- 12786468
TI  - Torus breakdown in noninvertible maps.
AB  - We propose a criterion for the destruction of a two-dimensional torus through the
      formation of an infinite set of cusp points on the closed invariant curves
      defining the resonance torus. This mechanism is specific to noninvertible maps.
      The cusp points arise when the tangent to the torus at the point of intersection
      with the critical curve L(0) coincides with the eigendirection corresponding to
      vanishing eigenvalue for the noninvertible map. Further parameter changes lead
      typically to the generation of loops (self-intersections of the invariant
      manifolds) followed by the transformation of the torus into a complex chaotic
      set.

PMID- 12786469
TI  - Signatures of chaotic tunneling.
AB  - Recent experiments with cold atoms provide a significant step toward a better
      understanding of tunneling when irregular dynamics is present at the classical
      level. In this paper, we lay out numerical studies that shed light on the
      previous experiments and help to clarify the underlying physics. This study also
      provides guidelines for future experiments.

PMID- 12786470
TI  - Relationship between directed percolation and the synchronization transition in
      spatially extended systems.
AB  - We study the nature of the synchronization transition in spatially extended
      systems by discussing a simple stochastic model. An analytic argument is put
      forward showing that, in the limit of discontinuous processes, the transition
      belongs to the directed percolation (DP) universality class. The analysis is
      complemented by a detailed investigation of the dependence of the first passage
      time for the amplitude of the difference field on the adopted threshold. We find
      the existence of a critical threshold separating the regime controlled by linear
      mechanisms from that controlled by collective phenomena. As a result of this
      analysis, we conclude that the synchronization transition belongs to the DP class
      also in continuous models. The conclusions are supported by numerical checks on
      coupled map lattices too.

PMID- 12786471
TI  - Noise-level estimation of time series using coarse-grained entropy.
AB  - We present a method of noise-level estimation that is valid even for high noise
      levels. The method makes use of the functional dependence of coarse-grained
      correlation entropy K2(epsilon ) on the threshold parameter epsilon. We show that
      the function K2(epsilon ) depends, in a characteristic way, on the noise standard
      deviation sigma. It follows that observing K2 (epsilon ) one can estimate the
      noise level sigma. Although the theory has been developed for the Gaussian noise
      added to the observed variable we have checked numerically that the method is
      also valid for the uniform noise distribution and for the case of Langevin
      equation corresponding to the dynamical noise. We have verified the validity of
      our method by applying it to estimate the noise level in several chaotic systems
      and in the Chua electronic circuit contaminated by noise.

PMID- 12786472
TI  - Entrainment control in a noisy neural system.
AB  - The open-plus-closed-loop (OPCL) entrainment control put forth by Jackson and
      Grosu [Physica D 85, 1 (1995)] is applied to an effective-neuron system as a way
      to extract stable limit cycles from a chaotic attractor, analogous to the
      retrieval of memories from a memory searching state. Additive Gaussian white
      noise, representing the natural noise inherent in any real dynamical system, is
      added to the entrainment control mechanism. Moderate levels of additive noise
      have little effect on successful entrainment, as reflected in phase-space plots
      and Lyapunov exponents. All three Lyapunov exponents are negative, which suggests
      parallels between OPCL control and chaotic synchronization.

PMID- 12786473
TI  - Quantum computing of quantum chaos in the kicked rotator model.
AB  - We investigate a quantum algorithm that simulates efficiently the quantum kicked
      rotator model, a system that displays rich physical properties and enables to
      study problems of quantum chaos, atomic physics, and localization of electrons in
      solids. The effects of errors in gate operations are tested on this algorithm in
      numerical simulations with up to 20 qubits. In this way various physical
      quantities are investigated. Some of them, such as second moment of probability
      distribution and tunneling transitions through invariant curves, are shown to be
      particularly sensitive to errors. However, investigations of the fidelity and the
      Wigner and Husimi distributions show that these physical quantities are robust in
      presence of imperfections. This implies that the algorithm can simulate the
      dynamics of quantum chaos in presence of a moderate amount of noise.

PMID- 12786474
TI  - Evanescent wave approach to diffractive phenomena in convex billiards with
      corners.
AB  - What we are going to call in this paper "diffractive phenomena" in billiards is
      far from being deeply understood. These are sorts of singularities that, for
      example, some kind of corners introduce in the energy eigenfunctions. In this
      paper we use the well-known scaling quantization procedure to study them. We show
      how the scaling method can be applied to convex billiards with corners, taking
      into account the strong diffraction at them and the techniques needed to solve
      their Helmholtz equation. As an example, we study a classically pseudointegrable
      billiard, the truncated triangle. Then we focus our attention on the spectral
      behavior. A numerical study of the statistical properties of high-lying energy
      levels is carried out. It is found that all computed statistical quantities are
      roughly described by the so-called semi-Poisson statistics, but it is not clear
      whether the semi-Poisson statistics is the correct one in the semiclassical
      limit.

PMID- 12786475
TI  - Optimal control of the transient behavior of coupled solid-state lasers.
AB  - We apply optimal control theory to substantially reduce transient times for
      transitions between in-phase and out-of-phase states in coupled solid-state
      lasers. The control is a time-varying optical field that is injected into the
      cavities of each laser. We have analytically derived the optimal control and
      numerically solved the optimality system. Numerical simulations indicate that
      transient times can be significantly reduced upon increasing the injection
      strength very briefly.

PMID- 12786476
TI  - Pattern dynamics associated with on-off convection in a one-dimensional system.
AB  - A numerical and theoretical analysis of the phenomenologically constructed
      nonlinear stochastic model of on-off intermittency experimentally observed by
      John et al. in the electrohydrodynamic convection in nematic liquid crystal under
      applied dichotomous electric field is carried out. The model has the structure of
      the one-dimensional Swift-Hohenberg equation with a fluctuating threshold which
      represents an applied electric field and either with or without additive noise
      which corresponds to thermal noise. It is found that the fundamental statistics
      of pattern dynamics without additive noise agree with those experimentally
      observed, and also with those reported previously in two-dimensional system. In
      contrast to that the presence of multiplicative noise generates an intermittent
      evolution of pattern intensity, whose statistics are in agreement with those of
      on-off intermittency so far known, the additive noise gives rise to the change of
      position of the convective pattern. It is found that the temporal evolution of
      the phase suitably introduced to describe the global convective pattern also
      shows an intermittent evolution. Its statistics are studied in a detailed way
      with numerical simulation and stochastic analysis. The comparison of these
      results turn out to be in good agreement with each other.

PMID- 12786477
TI  - Controlling turbulence in a surface chemical reaction by time-delay
      autosynchronization.
AB  - A global time-delay feedback scheme is implemented experimentally to control
      chemical turbulence in the catalytic CO oxidation on a Pt(110) single crystal
      surface. The reaction is investigated under ultrahigh vacuum conditions by means
      of photoemission electron microscopy. We present results showing that turbulence
      can be efficiently suppressed by applying time-delay autosynchronization.
      Hysteresis effects are found in the transition regime from turbulence to
      homogeneous oscillations. At optimal delay time, we find a discontinuity in the
      oscillation period that can be understood in terms of an analytical investigation
      of a phase equation with time-delay autosynchronization. The experimental results
      are reproduced in numerical simulations of a realistic reaction model.

PMID- 12786478
TI  - Universal spectral statistics of Andreev billiards: semiclassical approach.
AB  - The symmetry classification of complex quantum systems has recently been extended
      beyond the Wigner-Dyson classes. Several of the novel symmetry classes can be
      discussed naturally in the context of superconducting-normal hybrid systems such
      as Andreev billiards and graphs. In this paper, we give a semiclassical
      interpretation of their universal spectral form factors in the ergodic limit.

PMID- 12786479
TI  - Spontaneous structure formation in a network of dynamic elements.
AB  - To discover the generic behaviors of dynamic networks, we study a coupled map
      system with variable coupling strength. It is found that this system
      spontaneously forms various types of network structure according to the parameter
      values. Depending on the synchronized or desynchronized motion of unit dynamics,
      the network structure can be either static or dynamic. The separation of units
      into two groups, one composed of units with a large number of outgoing
      connections and the other units with little outgoing connections, is observed in
      dynamic structure. It is revealed that the mechanism for such separation is a
      positive feedback between unit and connection dynamics.

PMID- 12786480
TI  - Chaotic behavior, collective modes, and self-trapping in the dynamics of three
      coupled Bose-Einstein condensates.
AB  - The dynamics of the three coupled bosonic wells (trimer) containing N bosons is
      investigated within a standard (mean-field) semiclassical picture based on the
      coherent-state method. Various periodic solutions (configured as pi-like,
      dimerlike, and vortex states) representing collective modes are obtained
      analytically when the fixed points of trimer dynamics are identified on the
      N=const submanifold in the phase space. Hyperbolic, maximum and minimum points
      are recognized in the fixed-point set by studying the Hessian signature of the
      trimer Hamiltonian. The system dynamics in the neighborhood of periodic orbits
      (associated with fixed points) is studied via numeric integration of trimer
      motion equations, thus revealing a diffused chaotic behavior (not excluding the
      presence of regular orbits), macroscopic effects of population inversion, and
      self-trapping. In particular, the behavior of orbits with initial conditions
      close to the dimerlike periodic orbits shows how the self-trapping effect of
      dimerlike integrable subregimes is destroyed by the presence of chaos.

PMID- 12786481
TI  - Noise sensitivity of sub- and supercritically bifurcating patterns with group
      velocities close to the convective-absolute instability.
AB  - The influence of small additive noise on structure formation near a forwards and
      near an inverted bifurcation as described by a cubic and quintic Ginzburg Landau
      amplitude equation, respectively, is studied numerically for group velocities in
      the vicinity of the convective-absolute instability where the deterministic front
      dynamics would empty the system.

PMID- 12786482
TI  - Thermal convection in binary fluid mixtures with a weak concentration
      diffusivity, but strong solutal buoyancy forces.
AB  - Thermal convection in binary liquid mixtures is investigated in the limit where
      the solutal diffusivity is weak, but the separation ratio is large.
      Representative examples are colloidal suspensions such as ferrofluids. With a
      grain size being large on molecular length scales, the particle mobility is
      extremely small, allowing to disregard the concentration dynamics in most cases.
      However, this simplification does not hold for thermal convection: Due to the
      pronounced Soret effect of these materials in combination with a considerable
      solutal expansion, the resulting solutal buoyancy forces are dominant. Indeed,
      convective motion is found to set in at Rayleigh numbers well below the critical
      threshold for single-component liquids. A nonlinear analysis demonstrates that
      the amplitude quickly saturates in a state of stationary convective motion.

PMID- 12786483
TI  - Nonlinear dynamics of traveling waves in rotating Rayleigh-Benard convection:
      effects of the boundary conditions and of the topology.
AB  - Motivated by the experimental results of Liu and Ecke (1997, 1999), different
      models are developed to analyze the weakly nonlinear dynamics of the traveling
      wave sidewall modes appearing in rotating Rayleigh-Benard convection. These
      models assume fully rigid boundary conditions for the velocity field. At the
      linear level, this influences most strongly the critical frequencies: they appear
      to be proportional to the logarithm of the Coriolis number, which is twice the
      inverse of the Ekman number. An annular flow domain is considered. This multiply
      connected geometry is shown to lead generally to the existence of a global mean
      flow mode proportional to the average, over the azimuthal coordinate, of the
      square of the modulus of the envelope of the waves. Because this mode feeds back
      on the active wave modes at cubic order, the resulting Ginzburg-Landau envelope
      equation contains a nonlocal term. This new term, however, vanishes in the large
      gap limit relevant to the experiments of Liu and Ecke. As compared with previous
      theoretical work, the present models lead to reduced discrepancies with the
      results of these experiments concerning the coefficients of the envelope
      equation. It is also shown that the new nonlocal effects may be realized
      experimentally in a small-gap annular geometry if a small-Prandtl-number fluid is
      used, despite the fact that no regime of Benjamin-Feir instability is predicted
      to occur.

PMID- 12786484
TI  - Three-dimensional lattice-Boltzmann simulations of critical spinodal
      decomposition in binary immiscible fluids.
AB  - We use a modified Shan-Chen, noiseless lattice-BGK model for binary immiscible,
      incompressible, athermal fluids in three dimensions to simulate the coarsening of
      domains following a deep quench below the spinodal point from a symmetric and
      homogeneous mixture into a two-phase configuration. The model is derivable from a
      continuous-time Boltzmann-BGK equation in the presence of an intercomponent body
      force. We find the average domain size grows with time as t(gamma), where gamma
      increases in the range 0.545+/-0.014<gamma<0.717+/-0.002, consistent with a
      crossover between diffusive t(1/3) and hydrodynamic viscous, t(1.0), behavior. We
      find good collapse onto a single scaling function, yet the domain growth
      exponents differ from previous results for similar values of the unique
      characteristic length L0 and time T0 that can be constructed out of the fluid's
      parameters. This rebuts claims of universality for the dynamical scaling
      hypothesis. For Re=2.7 and small wave numbers q we also find a q(2)<-->q(4)
      crossover in the scaled structure function, which disappears when the dynamical
      scaling reasonably improves at later stages (Re=37). This excludes noise as the
      cause for a q(2) behavior, as analytically derived from Yeung and proposed by
      Appert et al. and Love et al. on the basis of their lattice-gas simulations. We
      also observe exponential temporal growth of the structure function during the
      initial stages of the dynamics and for wave numbers less than a threshold value,
      in accordance with the diffusive Cahn-Hilliard Model B. However, this exponential
      growth is also present in regimes proscribed by that model. There is no evidence
      that regions of parameter space for which the scheme is numerically stable become
      unstable as the simulations proceed, in agreement with finite-difference
      relaxational models and in contradistinction with an unconditionally unstable
      lattice-BGK free-energy model previously reported. Those numerical instabilities
      that do arise in this model are the result of large intercomponent forces which
      turn the equilibrium distribution negative.

PMID- 12786485
TI  - Landau damping and coherent structures in narrow-banded 1+1 deep water gravity
      waves.
AB  - We study the modulational instability in surface gravity waves with random phase
      spectra. Starting from the nonlinear Schrodinger equation and using the Wigner
      Moyal transform, we study the stability of the narrow-banded approximation of a
      typical wind-wave spectrum, i.e., the JONSWAP spectrum. By performing numerical
      simulations of the nonlinear Schrodinger equation we show that in the unstable
      regime, the nonlinear stage of the modulational instability is responsible for
      the formation of coherent structures. Furthermore, a Landau-type damping, due to
      the incoherence of the waves, whose role is to provide a stabilizing effect
      against the modulational instability, is both analytically and numerically
      discussed.

PMID- 12786486
TI  - Numerical studies of the transport behavior of a passive solute in a two
      dimensional incompressible random flow field.
AB  - We study the transport behavior of a passive scalar in a two-dimensional (2D)
      time-independent Gaussian random velocity field by efficient and highly accurate
      numerical simulations. The model under consideration has been used in order to
      gain basic understanding of transport processes in incompressible flow through
      heterogeneous porous media. The velocity field is derived from the linearized
      solution of the Darcy equation with a Gauss-distributed log-hydraulic
      conductivity. The transport of a passive scalar is studied by a high precision
      random-walk method, which allows for a systematic nonperturbative study of the
      ensemble and effective dispersion coefficients. The conclusive numerical results
      validate the range of applicability of the perturbation theory and the
      consistency of nonperturbative approaches to the transport problem in a random
      medium. Furthermore, we observe closed streamlines in incompressible 2D Gaussian
      random fields, which restricts the direct applicability of the simulation method
      for transport in heterogeneous porous media, and questions the results of similar
      studies that do not observe this phenomenon.

PMID- 12786487
TI  - Observation of electro-osmotic flow echoes in porous media by nuclear magnetic
      resonance.
AB  - A method for assessing the time reversibility of molecular displacements in
      fluids is presented. The method utilizes pulsed field gradient NMR experiments,
      in which the flow driving force is inverted during the magnetization lifetime in
      each measurement cycle. The method is suitable for opaque three-dimensional
      systems and short displacements, and provides inherent separation between thermal
      diffusion and displacements driven by externally controlled forces. This approach
      was applied to study the time reversibility of an electric-field-driven flow of
      water in natural sand samples, over time scales of up to 0.4 s and displacement
      scales of the order of one particle diameter. It is demonstrated that the
      intensity loss of the NMR signal, caused by flow-induced phase dispersion, is
      fully refocused upon inversion of the polarity of the applied electric field,
      resulting in flow echoes.

PMID- 12786488
TI  - Response maxima in modulated turbulence.
AB  - Isotropic and homogeneous turbulence driven by an energy input modulated in time
      is studied within a variable range mean-field theory. The response of the system,
      observed in the second-order moment of the large-scale velocity difference
      D(L,t)=<<(u(x+L)-u(x))(2)>> proportional, variant Re(2)(t), is calculated for
      varying modulation frequencies omega and weak modulation amplitudes. For low
      frequencies the system follows the modulation of the driving with almost constant
      amplitude, whereas for higher driving frequencies the amplitude of the response
      decreases on average proportional, variant 1/omega. In addition, at certain
      frequencies the amplitude of the response either almost vanishes or is strongly
      enhanced. These frequencies are connected with the frequency scale of the energy
      cascade and multiples thereof.

PMID- 12786489
TI  - Self-duality of the asymptotic relaxation states of fluids and plasmas.
AB  - The states of asymptotic relaxation of two-dimensional fluids and plasmas present
      a high degree of regularity and obedience to the sinh-Poisson equation. We find
      that by embedding the classical fluid description into a field-theoretical
      framework, the same equation appears as a manifestation of the self-duality.

PMID- 12786490
TI  - Boundary conditions for probability density function transport equations in fluid
      mechanics.
AB  - The behavior of the probability density function (PDF) transport equation at the
      limits of the probability space is studied from the point of view of fluid
      mechanics. Different boundary conditions are considered depending on the nature
      of the variable considered (velocity, scalar, and position). A study of the
      implications of entrance and exit conditions is performed, showing that a new
      term should be added to the PDF transport equation to preserve normalization in
      some nonstationary processes. In practice, this term is taken into account
      naturally in particle methods. Finally, the existence of discontinuities at the
      limits is also investigated.

PMID- 12786491
TI  - Diffusion in supersonic turbulent compressible flows.
AB  - We investigate diffusion in supersonic turbulent compressible flows. Supersonic
      turbulence can be characterized as network of interacting shocks. We consider
      flows with different rms Mach numbers and where energy necessary to maintain
      dynamical equilibrium is inserted at different spatial scales. We find that
      turbulent transport exhibits superdiffusive behavior due to induced bulk motions.
      In a comoving reference frame, however, diffusion behaves normal and can be
      described by mixing-length theory extended into the supersonic regime.

PMID- 12786492
TI  - Linear magnetohydrodynamic Taylor-Couette instability for liquid sodium.
AB  - The linear stability of MHD Taylor-Couette flow of infinite vertical extension is
      considered for liquid sodium with its small magnetic Prandtl number Pm of order
      10(-5). The calculations are performed for a container with R(out)=2R(in), with
      an axial uniform magnetic field and with boundary conditions for both vacuum and
      perfect conductions. For resting outer cylinder subcritical excitation in
      comparison to the hydrodynamical case occurs for large Pm but it disappears for
      small Pm. For rotating outer cylinder the Rayleigh line plays an exceptional
      role. The hydromagnetic instability exists with Reynolds numbers exactly scaling
      with Pm(-1/2) so that the moderate values of order 10(4) (for Pm=10(-5)) result.
      For the smallest step beyond the Rayleigh line, however, the Reynolds numbers
      scale as 1/Pm leading to much higher values of order 10(6). Then it is the
      magnetic Reynolds number Rm that directs the excitation of the instability. It
      results as lower for insulating than for conducting walls. The magnetic Reynolds
      number has to exceed here values of order 10 leading to frequencies of about 20
      Hz for the rotation of the inner cylinder if containers with (say) 10 cm radius
      are considered. With vacuum boundary conditions the excitation of nonaxisymmetric
      modes is always more difficult than the excitation of axisymmetric modes. For
      conducting walls, however, crossovers of the lines of marginal stability exist
      for both resting and rotating outer cylinders, and this might be essential for
      future dynamo experiments. In this case the instability also can onset as an
      overstability.

PMID- 12786493
TI  - Cellular flow patterns and their evolutionary scenarios in three-dimensional
      Rayleigh-Benard convection.
AB  - The evolution of three-dimensional, cellular convective flows in a plane
      horizontal layer of a Boussinesq fluid heated from below is studied numerically.
      Slow motion in the form of a spatially periodic pattern of hexagonal cells is
      introduced initially. In a further development, the flow can undergo a sequence
      of transitions between various cell types. The features of the flow evolution
      agree with the idea of the flow seeking an optimal scale. In particular, two
      vortex polygonal cells may form at some evolution stages, with an annular
      planform of the upflow region and downflows localized in both central and
      peripheral regions of the cells. If short-wave hexagons are stable, they exhibit
      a specific, stellate fine structure.

PMID- 12786494
TI  - Effect of particle inertia on turbulence in a suspension.
AB  - We propose a one-fluid analytical model for a turbulently flowing dilute
      suspension, based on a modified Navier-Stokes equation with a k-dependent
      effective density of suspension rho(eff)(k) and an additional damping term
      proportional, variant gamma(p)(k), representing the fluid-particle friction
      (described by Stokes law). The statistical description of turbulence within the
      model is simplified by a modification of the usual closure procedure based on the
      Richardson-Kolmogorov picture of turbulence with a differential approximation for
      the energy transfer term. The resulting ordinary differential equation for the
      energy budget is solved analytically for various important limiting cases and
      numerically in the general case. In the inertial interval of scales, we describe
      analytically two competing effects: the energy suppression due to the fluid
      particle friction and the energy enhancement during the cascade process due to
      decrease of the effective density of the small-scale motions. An additional
      suppression or enhancement of the energy density may occur in the viscous
      subrange, caused by the variation of the extent of the inertial interval due to
      the combined effect of the fluid-particle friction and the decrease of the
      kinematic viscosity of the suspensions. The analytical description of the
      complicated interplay of these effects supported by numerical calculations is
      presented. Our findings allow one to rationalize the qualitative picture of the
      isotropic homogeneous turbulence of dilute suspensions as observed in direct
      numerical simulations.

PMID- 12786495
TI  - Fully and partially non-neutral plasma equilibria in a variable-electrode-radius
      Malmberg-Penning trap.
AB  - Two types of plasma equilibria are self-consistently computed for a three
      electrode Malmberg-Penning trap that has an increase in the radius of a section
      of the center electrode. When a single species, fully non-neutral plasma is
      confined within the trap, equilibria are predicted in which the plasma produces a
      three-dimensional electric potential well. Partially non-neutral plasma
      equilibria are predicted to be possible by confining a second, oppositely signed
      plasma species within the three-dimensional well produced by the first plasma
      species. Conditions that are necessary for partially non-neutral plasma
      equilibria to be self-consistently possible are reported. A partially non-neutral
      plasma formed of electrons and singly charged xenon ions is then specifically
      considered, first with the ions confined within a three-dimensional well produced
      by the electrons and next with the electrons confined within a three-dimensional
      well produced by the ions.

PMID- 12786496
TI  - Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate
      tabletop-laser pulses interacting with solid targets.
AB  - Measurements of proton emission have been made from a variety of solid targets
      irradiated by a 60-fs, 200-mJ, 7 x 10(18)-W cm(-2) laser system operating at 2
      Hz. Optimum target conditions were found in terms of target material and
      thickness. For Mylar targets of thickness 20-40 microm, a maximum proton energy
      of 1.5 MeV was measured. For aluminum targets, a maximum energy of 950 keV was
      measured for 12 microm, and for copper, 850 keV for 12.5 microm.

PMID- 12786497
TI  - Fokker-Planck equation for Boltzmann-type and active particles: transfer
      probability approach.
AB  - A Fokker-Planck equation with velocity-dependent coefficients is considered for
      various isotropic systems on the basis of probability transition (PT) approach.
      This method provides a self-consistent and universal description of friction and
      diffusion for Brownian particles. Renormalization of the friction coefficient is
      shown to occur for two-dimensional and three-dimensional cases, due to the
      tensorial character of diffusion. The specific forms of PT are calculated for
      Boltzmann-type and absorption-type collisions (the latter are typical in dusty
      plasmas and some other systems). The validity of the Einstein's relation for
      Boltzmann-type collisions is analyzed for the velocity-dependent friction and
      diffusion coefficients. For Boltzmann-type collisions in the region of very high
      grain velocity as well as it is always for non-Boltzmann collisions, such as,
      absorption collisions, the Einstein relation is violated, although some other
      relations (determined by the structure of PT) can exist. The generalized friction
      force is investigated in dusty plasmas in the framework of the PT approach. The
      relation among this force, the negative collecting friction force, and scattering
      and collecting drag forces is established. The concept of probability transition
      is used to describe motion of active particles in an ambient medium. On basis of
      the physical arguments, the PT for a simple model of the active particle is
      constructed and the coefficients of the relevant Fokker-Planck equation are
      found. The stationary solution of this equation is typical for the simplest self
      organized molecular machines.

PMID- 12786498
TI  - Gibbs-Bogolyubov inequality and transport properties for strongly coupled Yukawa
      fluids.
AB  - The Gibbs-Bogolyubov inequality is used to establish a mapping between the Yukawa
      system and both the hard-sphere and the one-component reference systems. The
      transport coefficients of self-diffusion, shear viscosity, and thermal
      conductivity are computed for the Yukawa fluid using known properties of the
      reference systems. Comparisons are made with simulation results. For sufficiently
      strong screening, the hard-sphere reference system yields a lower upper bound of
      the Yukawa Helmholtz free energy and a better estimate of the Yukawa transport
      coefficients.

PMID- 12786499
TI  - Monte Carlo model of ion mobility and diffusion for low and high electric fields.
AB  - A Monte Carlo method is described to model the mobility and diffusion of ions
      drifting in response to an electric field in a neutral gas. The model uses a
      collision frequency that is dependent upon the ion velocity and neutral gas
      thermal velocity. When implemented with a constant collision cross section for
      momentum transfer, the model gives a mobility that is constant for small electric
      fields (those giving a subsonic drift velocity) and that for larger fields falls
      inversely with the square root of the electric field. For argon ions drifting in
      argon, the model gives a close agreement with experimental data for the mobility
      for a wide range of electric fields when implemented with an energy-dependent
      cross section. For modeling of transverse diffusion, agreement with data is
      improved if the collisions are a combination of idealized charge-exchange
      collisions and hard-sphere collisions.

PMID- 12786500
TI  - Parametric instabilities of circularly polarized Alfven waves in a relativistic
      electron-positron plasma.
AB  - Dispersion relation and nonlinear evolution of the parametric instabilities of
      circularly polarized Alfven waves in a relativistic electron-positron plasma are
      investigated by theoretical and numerical approaches. In the nonrelativistic
      limit, when 2omega(2)(p)>omega20, the characteristics of the instabilities are
      similar to those in an electron-ion plasma, except that the modulational
      instability takes place only if v(2)(s)<omega(2)(0)/k(2)(0), where omega(p) and
      v(s) denote the plasma frequency and the acoustic speed, and omega(0), k(0)
      indicate the frequency and the wave number of the parent wave. On the other hand,
      when 2omega(2)(p)<omega20, two new types of instabilities emerge between the
      parallel or antiparallel propagating Alfven-like waves and the parallel
      propagating Langmuir-like wave. The weakly relativistic effect is discussed for
      all the instabilities. The one-dimensional full particle simulation and
      bicoherence analysis of the simulation result suggest that successive decay via
      the interaction between the parallel propagating Langmuir-like wave and
      antiparallel propagating Alfven-like wave can efficiently generate a continuum of
      low frequency electromagnetic waves, which can interact with energetic particles.

PMID- 12786501
TI  - Oscillating Coulomb chain in a storage ring.
AB  - The dynamic behavior of a bunched one-dimensional crystalline beam is studied
      theoretically. It is shown that, owing to the existence of momentum dispersion, a
      Coulomb chain traveling in a storage ring performs a complex periodic oscillation
      whenever it is exposed to a longitudinal radio-frequency force. The equations of
      motion are derived to predict the oscillation pattern in an arbitrary lattice
      structure. The validity of the present theory is confirmed through multiparticle
      simulations. Various features of an oscillating string beam, such as the lattice
      parameter dependence of the orbit, the stability, and critical line density,
      etc., are also discussed.

PMID- 12786502
TI  - Deflections in magnet fringe fields.
AB  - A transverse multipole expansion is derived, including the longitudinal
      components necessarily present in regions of varying magnetic field profile. It
      can be used for exact numerical orbit following through the fringe-field regions
      of magnets whose end designs introduce no extraneous components, i.e., fields not
      required to be present by Maxwell's equations. Analytic evaluations of the
      deflections are obtained in various approximations. Mainly emphasized is a
      "straight-line approximation," in which particle orbits are treated as straight
      lines through the fringe-field regions. This approximation leads to a readily
      evaluated figure of merit, the ratio of rms end deflection to nominal body
      deflection, that can be used to determine whether or not a fringe field can be
      neglected. Deflections in "critical" cases (e.g., near intersection regions) are
      analyzed in the same approximation.

PMID- 12786503
TI  - Structure and correlations in two-dimensional classical artificial atoms confined
      by a Coulomb potential.
AB  - The ordering of N equally charged particles (-e) moving in two dimensions and
      confined by a Coulomb potential, resulting from a displaced positive charge Ze is
      discussed. This is a classical model system for atoms. We obtain the
      configurations of charged particles which, depending on the value of N and Z, may
      result in ring structures, hexagonal-type configurations, and for N/Z
      approximately 1 in an inner structure of particles which is separated by an outer
      ring of particles. For N/Z<<1, the Hamiltonian of the parabolic confinement case
      is recovered. For N/Z approximately 1, the configurations are very different from
      those found in the case of a parabolic confinement potential. A hydrodynamic
      analysis is presented in order to highlight the correlations effects.

PMID- 12786504
TI  - Polarization splitting of optical resonant modes in a-Si:H/a-SiO(x):H
      microcavities.
AB  - We present experimental and theoretical results on polarization splitting of
      optical resonant modes in a-Si:H/a-SiO(x):H microcavities. It is shown
      experimentally that the splitting sign and value can be controlled by varying the
      active layer thickness. The polarization splitting achieved in the microcavities
      is about 8 meV owing to a large optical contrast, which is the ratio of film
      refractive indices in the distributed Bragg reflectors. The experimental data and
      theoretical analysis show that the polarization splitting may be zero at a
      certain angle of incidence of light determined by the microcavity parameters. The
      measured and calculated resonant frequency values for TM and TE polarizations
      were used to find the optical thickness of the active layer and the stop-band
      center frequency of the Bragg reflector. The account of the active layer
      thickness fluctuations along the lateral direction provides a better fit between
      the experimental and theoretical spectra.

PMID- 12786505
TI  - Nonuniform dynamic gratings in photorefractive media with nonlocal response.
AB  - The amplitude of the phase dynamic grating is a nonuniform space distributed in
      photorefractive crystals with nonlocal response as a result of energy transfer
      between the interacted waves. The dynamical process of grating formation in the
      case of transmission two- and four-wave mixing is described by the damped sine
      Gordon equation that governs the soliton propagation. A stationary soliton
      solution for the grating amplitude profile was obtained. Experiments on
      observation of a nonuniform distribution of the grating amplitude through the
      crystal volume are presented. It is experimentally shown that the changes of the
      grating amplitude profile in dependence of input intensity ratio match the
      solutions of the damped sine-Gordon equation in steady state. The diffraction
      efficiency of energy transfer is determined by the value of the integral under
      the grating amplitude profile. The soliton profile is altered with changing input
      intensity ratio of recorded beams. It provides the effect of diffraction
      efficiency management by changing the half-width and the position of the soliton.
      The theory predicts a multisoliton behavior in reversible media with strong
      amplification gain that leads to auto-oscillations of output wave intensities.

PMID- 12786506
TI  - Instabilities and bifurcations of nonlinear impurity modes.
AB  - We study the structure and stability of nonlinear impurity modes in the discrete
      nonlinear Schrodinger equation with a single on-site nonlinear impurity
      emphasizing the effects of interplay between discreteness, nonlinearity, and
      disorder. We show how the interaction of a nonlinear localized mode (a discrete
      soliton or discrete breather) with a repulsive impurity generates a family of
      stationary states near the impurity site, as well as examine both theoretical and
      numerical criteria for the transition between different localized states via a
      cascade of bifurcations.

PMID- 12786507
TI  - Matrix formalism of electromagnetic wave propagation through multiple layers in
      the near-field region: application to the flat panel display.
AB  - We have developed an electromagnetic (EM) wave propagation theory through a
      single layer and multiple layers in the near-field and far-field regions, and
      have constructed a matrix formalism in terms of the boundary conditions of the EM
      waves. From the shielding efficiency (SE) against EM radiation in the near-field
      region calculated by using the matrix formalism, we propose that the effect of
      multiple layers yields enhanced shielding capability compared to a single layer
      with the same total thickness in conducting layers as the multiple layers. We
      compare the intensities of an EM wave propagating through glass coated with
      conducting indium tin oxide (ITO) on one side and on both sides, applying it to
      the electromagnetic interference (EMI) shielding filter in a flat panel display
      such as a plasma display panel (PDP). From the measured intensities of EMI noise
      generated by a PDP loaded with ITO coated glass samples, the two-side coated
      glass shows a lower intensity of EMI noise compared to the one-side coated glass.
      The result confirms the enhancement of the SE due to the effect of multiple
      layers, as expected in the matrix formalism of EM wave propagation in the near
      field region. In the far-field region, the two-side coated glass with ITO in
      multiple layers has a higher SE than the one-side coated glass with ITO, when the
      total thickness of ITO in both cases is the same.

PMID- 12786508
TI  - Theory for tailoring sonic devices: diffraction dominates over refraction.
AB  - Acoustic crystal devices, with dimensions on the order of several wavelengths,
      are studied by using the finite-difference time domain method in the moderately
      long wavelength propagation regime. From the focusing and imaging process
      performed by a square shaped lens, it is shown that diffractive effects dominate
      over those due to refraction. The major role of the device edge diffraction is
      shown by means of the well known Babinet principle. The first examples of imaging
      with a sonic plane lens, both with crystal structure and massive, and with an
      acoustic prism able to change the propagation direction of a plane wave, are
      presented.

PMID- 12786509
TI  - Photonic band structures solved by a plane-wave-based transfer-matrix method.
AB  - Transfer-matrix methods adopting a plane-wave basis have been routinely used to
      calculate the scattering of electromagnetic waves by general multilayer gratings
      and photonic crystal slabs. In this paper we show that this technique, when
      combined with Bloch's theorem, can be extended to solve the photonic band
      structure for 2D and 3D photonic crystal structures. Three different
      eigensolution schemes to solve the traditional band diagrams along high-symmetry
      lines in the first Brillouin zone of the crystal are discussed. Optimal rules for
      the Fourier expansion over the dielectric function and electromagnetic fields
      with discontinuities occurring at the boundary of different material domains have
      been employed to accelerate the convergence of numerical computation. Application
      of this method to an important class of 3D layer-by-layer photonic crystals
      reveals the superior convergency of this different approach over the conventional
      plane-wave expansion method.

PMID- 12786510
TI  - Analysis of mode structure in hollow dielectric waveguide fibers.
AB  - In this paper, we analyze the electromagnetic mode structure of an OmniGuide
      fiber-a hollow dielectric waveguide in which light is confined by a large index
      contrast omnidirectional dielectric mirror. In particular, we find that the modes
      in an OmniGuide fiber are similar to those in a hollow metallic waveguide in
      their symmetries, cutoff frequencies, and dispersion relations. We show that the
      differences can be predicted by a model based on a single parameter-the phase
      shift upon reflection from the dielectric mirror. The analogy to the metal
      waveguide extends to the transmission properties, resulting in the identification
      of the TE01 mode as the lowest-loss mode of the OmniGuide fiber.

PMID- 12786511
TI  - Vavilov-Cherenkov effect in a driven resonant medium.
AB  - The Vavilov-Cherenkov effect in a dispersive and resonant absorbing medium is
      substantially modified by the presence of an external electromagnetic field.
      Depending on the field parameters and configuration we anticipate a remarkable
      increase of the emission yield at resonance. Our predictions are implemented by
      numerical estimates for cuprous oxide (Cu2O) where the yield turns out to be one
      to two orders of magnitude that obtained in the absence of the field.

PMID- 12786512
TI  - Soliton "molecules": robust clusters of spatiotemporal optical solitons.
AB  - We show how to generate robust self-sustained clusters of soliton bullets
      spatiotemporal (optical or matter-wave) solitons. The clusters carry an orbital
      angular momentum being supported by competing nonlinearities. The "atoms" forming
      the "molecule" are fully three-dimensional solitons linked via a staircaselike
      macroscopic phase. Recent progress in generating atomic-molecular coherent mixing
      in the Bose-Einstein condensates might open potential scenarios for the
      experimental generation of these soliton molecules with matter waves.

PMID- 12786513
TI  - Polarization filtering induced by imaging systems: effect on image structure.
AB  - In this paper are reported the results concerning the experimental study of the
      interaction between the vectorial amplitude of an optical field and imaging
      systems. It is shown that far-field as well as near-field imaging systems beside
      their spatial frequency filtering ability, also act as polarization filters
      playing a determinant role on the image structure. This conclusion is drawn from
      an experimental and theoretical study involving a radially polarized Bessel beam
      used as a test object.

PMID- 12786514
TI  - Existence and stability of discrete gap breathers in a diatomic beta Fermi-Pasta
      Ulam chain.
AB  - We study the existence and stability of discrete breathers in a chain consisting
      of alternating light and heavy particles, with nearest-neighbor coupling
      containing quartic soft or hard anharmonicity. This study is focused on breathers
      with frequency in the gap that separates the acoustic and optical bands of the
      phonon spectrum. Simple analytical and physical results obtained through explicit
      solutions of algebraic equations demonstrate the possibility of the existence of
      gap breathers with both types of symmetry, i.e., symmetric and antisymmetric. The
      specific pattern depends on the type of anharmonicity present, i.e., soft or
      hard, and whether the center of the breather is on a light or a heavy particle.
      These analytical results are verified systematically through the use of a
      numerically exact procedure from the anticontinuous limit.

PMID- 12786515
TI  - Dielectric profile variations in high-index-contrast waveguides, coupled mode
      theory, and perturbation expansions.
AB  - Perturbation theory formulation of Maxwell's equations gives a theoretically
      elegant and computationally efficient way of describing small imperfections and
      weak interactions in electromagnetic systems. It is generally appreciated that
      due to the discontinuous field boundary conditions in the systems employing high
      dielectric contrast profiles standard perturbation formulations fails when
      applied to the problem of shifted material boundaries. In this paper we developed
      coupled mode and perturbation theory formulations for treating generic
      perturbations of a waveguide cross section based on Hamiltonian formulation of
      Maxwell equations in curvilinear coordinates. We show that our formulation is
      accurate beyond the first order and rapidly converges to an exact result when
      used in a coupled mode theory framework even for the high-index-contrast
      discontinuous dielectric profiles. Among others, our formulation allows for an
      efficient numerical evaluation of such quantities as deterministic PMD and change
      in the GV and GVD of a mode due to generic profile distortion in a waveguide of
      arbitrary cross section. To our knowledge, this is the first time perturbation
      and coupled mode theories are developed to deal with arbitrary profile variations
      in high-index-contrast waveguides.

PMID- 12786516
TI  - Inverse scattering theory: renormalization of the Lippmann-Schwinger equation for
      acoustic scattering in one dimension.
AB  - The most robust treatment of the inverse acoustic scattering problem is based on
      the reversion of the Born-Neumann series solution of the Lippmann-Schwinger
      equation. An important issue for this approach to inversion is the radius of
      convergence of the Born-Neumann series for Fredholm integral kernels, and
      especially for acoustic scattering for which the interaction depends on the
      square of the frequency. By contrast, it is well known that the Born-Neumann
      series for the Volterra integral equations in quantum scattering are absolutely
      convergent, independent of the strength of the coupling characterizing the
      interaction. The transformation of the Lippmann-Schwinger equation from a
      Fredholm to a Volterra structure by renormalization has been considered
      previously for quantum scattering calculations and electromagnetic scattering. In
      this paper, we employ the renormalization technique to obtain a Volterra equation
      framework for the inverse acoustic scattering series, proving that this series
      also converges absolutely in the entire complex plane of coupling constant and
      frequency values. The present results are for acoustic scattering in one
      dimension, but the method is general. The approach is illustrated by applications
      to two simple one-dimensional models for acoustic scattering.

PMID- 12786517
TI  - Soliton propagation in a medium with Kerr nonlinearity and resonant impurities: a
      variational approach.
AB  - Using a variational approach we have studied the shape preserving coherent
      propagation of light pulses in a resonant dispersive medium in the presence of
      the Kerr nonlinearity. Within the framework of a combined nonintegrable system
      composed of one nonlinear Schrodinger and a pair of Bloch equations, we show the
      existence of a solitary wave. We have tested our analytical solution through
      numerical simulations confirming its solitary wave nature.

PMID- 12786518
TI  - Observation of multiple soliton generation mediated by amplification of
      asymmetries.
AB  - We report the experimental observation of the formation of multiple optical
      quadratic solitons in a process mediated by the amplification of minute
      asymmetries in the diffraction properties of the input light. Experiments were
      conducted in phase-matched second-harmonic generation in a bulk crystal of
      periodically poled potassium titanyl phosphate pumped at 1064 nm. The different
      mechanisms that influence the process were investigated numerically, and the
      pulsed nature of the pump light was found to play a key role in the observed
      light distributions.

PMID- 12786519
TI  - Exact soliton solutions of coupled nonlinear Schrodinger equations: shape
      changing collisions, logic gates, and partially coherent solitons.
AB  - The different dynamical features underlying soliton interactions in coupled
      nonlinear Schrodinger equations, which model multimode wave propagation under
      varied physical situations in nonlinear optics, are studied. In this paper, by
      explicitly constructing multisoliton solutions (up to four-soliton solutions) for
      two-coupled and arbitrary N-coupled nonlinear Schrodinger equations using the
      Hirota bilinearization method, we bring out clearly the various features
      underlying the fascinating shape changing (intensity redistribution) collisions
      of solitons, including changes in amplitudes, phases and relative separation
      distances, and the very many possibilities of energy redistributions among the
      modes of solitons. However, in this multisoliton collision process the pairwise
      collision nature is shown to be preserved in spite of the changes in the
      amplitudes and phases of the solitons. Detailed asymptotic analysis also shows
      that when solitons undergo multiple collisions, there exists the exciting
      possibility of shape restoration of at least one soliton during interactions of
      more than two solitons represented by three- and higher-order soliton solutions.
      From an application point of view, we have shown from the asymptotic expressions
      how the amplitude (intensity) redistribution can be written as a generalized
      linear fractional transformation for the N-component case. Also we indicate how
      the multisolitons can be reinterpreted as various logic gates for suitable
      choices of the soliton parameters, leading to possible multistate logic. In
      addition, we point out that the various recently studied partially coherent
      solitons are just special cases of the bright soliton solutions exhibiting shape
      changing collisions, thereby explaining their variable profile and shape
      variation in collision process.

PMID- 12786520
TI  - Laser characterization of ultrasonic wave propagation in random media.
AB  - Lasers can be used to excite and detect ultrasonic waves in a wide variety of
      materials. This allows the measurement of absolute particle motion without the
      mechanical disturbances of contacting transducers. In an ultrasound transmission
      experiment, the wave field is usually accessible only on the boundaries of a
      sample. Using optical methods, one can measure the surface wave field, in effect,
      within the scattering region. Here, we describe noncontacting (laser source and
      detector) measurements of ultrasonic wave propagation in randomly heterogeneous
      rock samples. By scanning the surface of the sample, we can directly visualize
      the complex dynamics of diffraction, multiple scattering, mode conversion, and
      whispering gallery modes. We will show measurements on rock samples that have
      similar elastic moduli and intrinsic attenuation, but different grain sizes, and
      hence, different scattering strengths. The intensity data are well fit by a
      radiative transfer model, and we use this fact to infer the scattering mean free
      path.

PMID- 12786521
TI  - Iterative approach to Maxwell equations for dielectric media of spatially varying
      refractive index.
AB  - We propose an iterative method to solve the Maxwell equations for a one
      dimensional model system with spatially varying permittivity. We construct
      solutions that are iterative in the scattering order, equivalent to the number of
      scattering events along the forward and backward directions. A numerical
      implementation of this approach is also presented.

PMID- 12786522
TI  - Radiative scattering properties of an ensemble of variously shaped small
      particles.
AB  - This paper presents a rigorous solution to the scattering of a monochromatic
      plane wave by an arbitrary configuration of wavelength-sized small particles that
      can be of different shape, structure, size, and composition. A T-matrix
      formulation is developed for the calculation of optical cross sections and the
      asymmetry parameter of such an ensemble of scatterers in both fixed and random
      orientations. The solution is based on the T matrix T(jl), that is, the inverse
      of the coefficient matrix of boundary condition equations. A linear system
      containing T(jl) is derived to efficiently solve the T matrix, which is required
      in the practical implementation of the solution.

PMID- 12786523
TI  - Directed loop updates for quantum lattice models.
AB  - This article outlines how the quantum Monte Carlo directed loop update recently
      introduced can be applied to a wide class of quantum lattice models. Several
      models are considered: spin-s XXZ models with longitudinal and transverse
      magnetic fields, boson models with two-body interactions, and one-dimensional
      spinful fermion models. Expressions are given for the parameter regimes where
      very efficient "no-bounce" quantum Monte Carlo algorithms can be found.

PMID- 12786524
TI  - Quantum dynamics under the influence of external magnetic fields.
AB  - In this paper, we describe a very versatile numerical model, which can be applied
      to study the quantum dynamics of an electron wave packet in the presence of
      external electric and magnetic fields. Detailed numerical analysis is carried out
      in the paper on the validity of such a model, including (1). comparison with
      analytical solution in the case of uniform magnetic field, and (2). stringent
      numerical tests in the case of both electric and magnetic fields. The algorithm
      presented here is found to be highly accurate, computationally efficient, and
      numerically stable. It also has the advantage of being able to accommodate
      arbitrarily complex magnetic field profiles as well as time-varying external
      fields.

PMID- 12786525
TI  - Algorithmic scalability in globally constrained conservative parallel discrete
      event simulations of asynchronous systems.
AB  - We consider parallel simulations for asynchronous systems employing L processing
      elements that are arranged on a ring. Processors communicate only among the
      nearest neighbors and advance their local simulated time only if it is guaranteed
      that this does not violate causality. In simulations with no constraints, in the
      infinite L limit the utilization scales [Korniss et al., Phys. Rev. Lett. 84,
      1351 (2000)]; but, the width of the virtual time horizon diverges (i.e., the
      measurement phase of the algorithm does not scale). In this work, we introduce a
      moving Delta-window global constraint, which modifies the algorithm so that the
      measurement phase scales as well. We present results of systematic studies in
      which the system size (i.e., L and the volume load per processor) as well as the
      constraint are varied. The Delta constraint eliminates the extreme fluctuations
      in the virtual time horizon, provides a bound on its width, and controls the
      average progress rate. The width of the Delta window can serve as a tuning
      parameter that, for a given volume load per processor, could be adjusted to
      optimize the utilization, so as to maximize the efficiency. This result may find
      numerous applications in modeling the evolution of general spatially extended
      short-range interacting systems with asynchronous dynamics, including dynamic
      Monte Carlo studies.

PMID- 12786526
TI  - Continuum-particle hybrid coupling for mass, momentum, and energy transfers in
      unsteady fluid flow.
AB  - The aim of hybrid methods in simulations is to communicate regions with disparate
      time and length scales. Here, a fluid described at the atomistic level within an
      inner region P is coupled to an outer region C described by continuum fluid
      dynamics. The matching of both descriptions of matter is made across an
      overlapping region and, in general, consists of a two-way coupling scheme (C-->P
      and P-->C) that conveys mass, momentum, and energy fluxes. The contribution of
      the hybrid scheme hereby presented is twofold. First, it treats unsteady flows
      and, more importantly, it handles energy exchange between both C and P regions.
      The implementation of the C-->P coupling is tested here using steady and unsteady
      flows with different rates of mass, momentum and energy exchange. In particular,
      relaxing flows described by linear hydrodynamics (transversal and longitudinal
      waves) are most enlightening as they comprise the whole set of hydrodynamic
      modes. Applying the hybrid coupling scheme after the onset of an initial
      perturbation, the cell-averaged Fourier components of the flow variables in the P
      region (velocity, density, internal energy, temperature, and pressure) evolve in
      excellent agreement with the hydrodynamic trends. It is also shown that the
      scheme preserves the correct rate of entropy production. We discuss some general
      requirements on the coarse-grained length and time scales arising from both the
      characteristic microscopic and hydrodynamic scales.

PMID- 12786527
TI  - Determination of the composition of light thin films with artificial neural
      network analysis of Rutherford backscattering experiments.
AB  - AlO(x)N(y) ultrathin films are used as insulating layers in advanced
      microelectronic devices. Structural characterization of these films is often done
      by the Rutherford backscattering (RBS) analysis. The RBS analysis of these
      oxinitrides is a difficult task since the relevant signals of the spectrum are
      washed out by the large substrate background and a considerable time is required
      for an analyst to characterize the sample. In this work we developed specialized
      artificial neural networks that are able to perform a fast and efficient analysis
      of the data. The results are in good agreement with traditional methods.

PMID- 12786528
TI  - Spectral method for the time-dependent Gross-Pitaevskii equation with a harmonic
      trap.
AB  - We study the numerical resolution of the time-dependent Gross-Pitaevskii
      equation, a nonlinear Schrodinger equation used to simulate the dynamics of Bose
      Einstein condensates. Considering condensates trapped in harmonic potentials, we
      present an efficient algorithm by making use of a spectral-Galerkin method, using
      a basis set of harmonic-oscillator functions, and the Gauss-Hermite quadrature.
      We apply this algorithm to the simulation of condensate breathing and scissor
      modes.

PMID- 12786529
TI  - Infinitely fast diffusion in single-file systems.
AB  - We have used dynamic Monte Carlo(DMC) methods and analytical techniques to
      analyze single-file systems for which diffusion is infinitely fast. We have
      simplified the master equation removing the fast reactions, and we have
      introduced a DMC algorithm for infinitely fast diffusion. The DMC method for fast
      diffusion give similar results as the standard DMC with high diffusion rates. We
      have investigated the influence of characteristic parameters, such as pipe
      length, adsorption, desorption, and conversion rate constants on the steady-state
      properties of single-file systems with a reaction, looking at cases when all the
      sites are reactive and when only some of them are reactive. We find that the
      effect of fast diffusion on single-file properties of the system is absent even
      when diffusion is infinitely fast. Diffusion is not important in these systems.
      Smaller systems are less reactive and the occupancy profiles for infinitely long
      systems show an exponential behavior.

PMID- 12786530
TI  - Fracture flow simulation using a finite-difference lattice Boltzmann method.
AB  - We present numerical computations for single phase flow through three-dimensional
      digitized rock fractures under varied simulated confining pressures appropriate
      to midcrustal depths. The computations are performed using a finite difference,
      lattice Boltzmann method and thus simulate Navier-Stokes flow. The digitized
      fracture data sets come from profiled elevations taken on tensile induced
      fractures in Harcourt granite. Numerical predictions of fracture permeability are
      compared with laboratory measurements performed on the same fractures. Use of the
      finite difference lattice Boltzmann method allows computation on nonuniform grid
      spacing, enabling accurate resolution across the aperture width without extensive
      refinement in the other two directions.

PMID- 12786531
TI  - Random symmetric matrices with a constraint: the spectral density of random
      impedance networks.
AB  - We derive the mean eigenvalue density for symmetric Gaussian random N x N
      matrices in the limit of large N, with a constraint implying that the row sum of
      matrix elements should vanish. The result is shown to be equivalent to a result
      found recently for the average density of resonances in random impedance networks
      [Y.V. Fyodorov, J. Phys. A 32, 7429 (1999)]. In the case of banded matrices, the
      analytical results are compared with those extracted from the numerical solution
      of Kirchhoff equations for quasi-one-dimensional random impedance networks.

PMID- 12786532
TI  - Mean-field approximation to a spatial host-pathogen model.
AB  - We study the mean-field approximation to a simple spatial host-pathogen model
      that has been shown to display interesting evolutionary properties. We show that
      previous derivations of the mean-field equations for this model are actually only
      low-density approximations to the true mean-field limit. We derive the correct
      equations and the corresponding equations including pair correlations. The
      process of invasion by a mutant type of pathogen is also discussed.

PMID- 12786533
TI  - Information content in the Nagel-Schreckenberg cellular automaton traffic model.
AB  - We estimate the set dimension and find bounds for the set entropy of a cellular
      automaton model for single lane traffic. Set dimension and set entropy, which are
      measures of the information content per cell, are related to the fractal nature
      of the automaton [S. Wolfram, Physica D 10, 1 (1989); Theory and Application of
      Cellular Automata, edited by S. Wolfram (World Scientific, Philadelphia, 1986)]
      and have practical implications for data compression. For models with maximum
      speed v(max), the set dimension is approximately log((v(max)+2))2.5, which is
      close to one bit per cell regardless of the maximum speed. For a typical maximum
      speed of five cells per time step, the dimension is approximately 0.47.

PMID- 12786534
TI  - Solvable model in renormalization group analysis for effective eddy viscosity.
AB  - This study presents a solvable model in renormalization group analysis for the
      effective eddy viscosity. It is found fruitful to take a simple hypothesis that
      large-scale eddies are statistically independent of those of smaller scales. A
      limiting operation of renormalization group analysis yields an inhomogeneous
      ordinary differential equation for the invariant effective eddy viscosity. The
      closed-form solution of the equation facilitates derivations of an expression of
      the Kolmogorov constant C(K) and of the Smagorinsky model for large-eddy
      simulation of turbulent flow. The Smagorinsky constant C(S) is proportional to
      C(3/4)(K). In particular, we shall illustrate that the value of C(K) ranges from
      1.35 to 2.06, which is in close agreement with the generally accepted
      experimental values (1.2 approximately 2.2).

PMID- 12786535
TI  - Decay of counterflow He II turbulence in a finite channel: possibility of missing
      links between classical and quantum turbulence.
AB  - Decay of He II counterflow turbulence generated by applying a heat pulse to the
      closed end of a circular channel is investigated using second sound attenuation.
      Several orders of magnitude of decaying vortex line density display various
      regimes, starting with the inverse time decay predicted by Vinen towards distinct
      classical t(-3/2) power law occurring after saturation of the energy containing
      length scale by the size of the channel. The decaying counterflow turbulence
      displays a surprisingly close resemblance to recently reported decaying grid
      turbulence in He II, and both of them appear closely linked to classical grid
      generated turbulence.

PMID- 12786536
TI  - Strong double-layer formation by shock waves in nonequilibrium plasmas.
AB  - Strong double-layer formation by acoustic shock wave (<M=2) propagation in a low
      pressure, N2 positive column plasma has been quantified, near the shock front, by
      measurements of the voltage jump and the enhancements of both the B (3)Pi(g)-A
      (3)Sigma(+)(u) plasma emission and the electron density. The large polarity
      dependence (or shock direction) of these effects and potential jumps of more than
      20 kT(e) across the shock-created interface indicate that the measured shock
      induced electron heating effects (localized excitation and ionization rate) are
      caused by the formation of strong double layers maintained by the traveling shock
      front.

PMID- 12786537
TI  - Nonlinear stability of solitons against strong external perturbations.
AB  - We study soliton stability under the action of strong external perturbations.
      Limits on the weak perturbation approach are established with the help of average
      Lagrangian methods and full simulations. We found that for the same relative
      perturbation, larger amplitude solitons develop instability earlier than weaker
      amplitude solitons.

PMID- 12786538
TI  - Coupling fields and underlying space curvature: an augmented Lagrangian approach.
AB  - We demonstrate a systematic implementation of coupling between a scalar field and
      the geometry of the space which carries the field. This naturally gives rise to a
      feedback mechanism between the field and the geometry. We develop a systematic
      model for the feedback in a general form, inspired by a specific implementation
      in the context of molecular dynamics (the so-called Rahman-Parrinello molecular
      dynamics, or RP-MD). We use a generalized Lagrangian that allows for the coupling
      of the space's metric tensor to the scalar field, and add terms motivated by RP
      MD. We present two implementations of the scheme: one in which the metric is only
      time-dependent (which gives rise to an ordinary differential equation for its
      temporal evolution), and the other with spatiotemporal dependence (wherein the
      metric's evolution is governed by a partial differential equation). Numerical
      results are reported for the (1+1)-dimensional model with a nonlinearity of the
      sine-Gordon type.

PMID- 12786539
TI  - Fast monte carlo simulations and singularities in the probability distributions
      of nonequilibrium systems.
AB  - A numerical technique is introduced that reduces exponentially the time required
      for Monte Carlo simulations of nonequilibrium systems. Results for the
      quasistationary probability distribution in two model systems are compared with
      the asymptotically exact theory in the limit of extremely small noise intensity.
      Singularities of the nonequilibrium distributions are revealed by the
      simulations.

PMID- 12786540
TI  - Quantum oscillations without quantum coherence.
AB  - We study numerically the damping of quantum oscillations and the dynamics of the
      density matrix in model many-spin systems decohered by a spin bath. We show that
      oscillations of some density matrix elements can persist with considerable
      amplitude long after other elements, along with the entropy, have come close to
      saturation, i.e., when the system has been decohered almost completely. The
      oscillations exhibit very slow decay, and may be observable in experiments.

PMID- 12786541
TI  - Microscopic structure of a vortex line in a dilute superfluid fermi gas.
AB  - The microscopic properties of a single vortex in a dilute superfluid Fermi gas at
      zero temperature are examined within the framework of self-consistent Bogoliubov
      de Gennes theory. Using only physical parameters as input, we study the pair
      potential, the density, the energy, and the current distribution. Comparison of
      the numerical results with analytical expressions clearly indicates that the
      energy of the vortex is governed by the zero-temperature BCS coherence length.

PMID- 12786542
TI  - Universal behavior of crossover scaling functions for continuous phase
      transitions.
AB  - We consider two different systems exhibiting a continuous phase transition into
      an absorbing state. Both models belong to the same universality class; i.e., they
      are characterized by the same scaling functions and the same critical exponents.
      Varying the range of interactions, we examine the crossover from the mean-field
      like to the non-mean-field scaling behavior. A phenomenological scaling form is
      applied in order to describe the full crossover region, which spans several
      decades. Our results strongly support the hypothesis that the crossover function
      is universal.

PMID- 12786543
TI  - Current noise in ac-driven nanoscale conductors.
AB  - The theory for current fluctuations in ac-driven transport through nanoscale
      systems is put forward. By use of a generalized, non-Hermitian Floquet theory we
      derive novel explicit expressions for the time-averaged current and the zero
      frequency component of the power spectrum of current fluctuations. A distinct
      suppression of both the zero-frequency noise and the dc current occurs for
      suitably tailored ac fields. The relative level of transport noise, being
      characterized by a Fano factor, can selectively be manipulated by ac sources; in
      particular, it exhibits both characteristic maxima and minima near current
      suppression.

PMID- 12786544
TI  - Is there nuclear pinning of vortices in superfluid pulsars?
AB  - We develop a fully consistent semianalytical model in order to study the vortex
      nucleus interaction in the inner crust of neutron stars. In the framework of the
      local-density approximation and assuming a constant pairing gap and a square-well
      nuclear potential, the model takes into account all energy contributions and
      determines unambiguously the structure of the vortex core. The results show that,
      irrespective of the value of the pairing gap, only interstitial pinning takes
      place all along the inner crust. This is in contrast with all existing
      calculations, which predict nuclear pinning in the deeper layers of the crust.
      Should further studies confirm this surprising result, the explanation of pulsar
      glitches in terms of depinning of vortices will have to be carefully revisited.

PMID- 12786545
TI  - Fine structure of dark matter halos and its effect on terrestrial detection
      experiments.
AB  - Terrestrial dark matter detection experiments probe the velocity-space
      distribution of dark matter particles in the vicinity of the Earth. We present a
      novel method, to be used in conjunction with standard cosmological simulations of
      hierarchical clustering, that allows one to extract a truly local velocity-space
      distribution in exquisite detail. Preliminary results suggest a new picture for
      this distribution which is decidedly non-Maxwellian but instead is characterized
      by randomly positioned peaks in velocity space. We discuss the implications of
      these results for experiments to detect axions and weakly interacting massive
      particles.

PMID- 12786546
TI  - Ultraviolet modifications of dispersion relations in effective field theory.
AB  - The existence of a fundamental ultraviolet scale, such as the Planck scale, may
      lead to modifications of the dispersion relations for particles at high energies
      in some scenarios of quantum gravity. We apply effective field theory to this
      problem and identify dimension-5 operators that do not mix with dimensions 3 and
      4 and lead to cubic modifications of dispersion relations for scalars, fermions,
      and vector particles. Further we show that, for electrons, photons and light
      quarks, clock comparison experiments bound these operators at 10(-5)/M(Pl).

PMID- 12786547
TI  - Heavy-quarkonium creation and annihilation with O(alpha(3)(s)ln(alpha(s))
      accuracy.
AB  - We calculate the O(alpha(3)(s)ln(alpha(s)) contributions to the heavy-quarkonium
      production and annihilation rates. Our result sheds new light on the structure of
      the high-order perturbative corrections and opens a new perspective for a high
      precision theoretical analysis. We also determine the three-loop anomalous
      dimensions of the nonrelativistic vector and pseudoscalar currents.

PMID- 12786548
TI  - Centrality scaling of the p(T) distribution of pions.
AB  - From the preliminary data of PHENIX on the centrality dependence of the pi(0)
      spectrum in p(T) at midrapidity in heavy-ion collisions, we show that a scaling
      behavior exists that is independent of the centrality. It is then shown that
      <p(T)> degrades with increasing N(part) exponentially with a decay constant that
      can be quantified. A scaling distribution in terms of an intuitive scaling
      variable is derived that is analogous to the Koba-Nielsen-Olesen scaling. No
      theoretical models are used in any part of this phenomenological analysis.

PMID- 12786549
TI  - Experimental indications for the response of the spectators to the participant
      blast.
AB  - Precise momentum distributions of identified projectile fragments, formed in the
      reactions 238U+Pb and 238U+Ti at 1A GeV, are measured with a high-resolution
      magnetic spectrometer. With increasing mass loss, the velocities first decrease
      as expected from previously established systematics, then level off, and finally
      increase again. Light fragments are on the average even faster than the
      projectiles. This finding is interpreted as the response of the spectators to the
      participant blast. The reacceleration of projectile spectators is sensitive to
      the nuclear mean field and provides a new tool for investigating the equation of
      state of nuclear matter.

PMID- 12786550
TI  - Critical-point symmetry in a finite system.
AB  - At a critical point of a second-order phase transition the intrinsic energy
      surface is flat and there is no stable minimum value of the deformation. However,
      for a finite system, we show that there is an effective deformation which can
      describe the dynamics at the critical point. This effective deformation is
      determined by minimizing the energy surface after projection onto the appropriate
      symmetries. We derive analytic expressions for energies and quadrupole rates
      which provide good estimates for these observables at the critical point.

PMID- 12786551
TI  - Molecular alignment by trains of short laser pulses.
AB  - We show that a dramatic field-free molecular alignment can be achieved after
      exciting molecules with proper trains of strong ultrashort laser pulses. Optimal
      two- and three-pulse excitation schemes are defined, providing an efficient and
      robust molecular alignment. This opens new prospects for various applications
      requiring macroscopic ensembles of highly aligned molecules.

PMID- 12786552
TI  - New bloch period for interacting cold atoms in 1D optical lattices.
AB  - This paper studies Bloch oscillations of ultracold atoms in an optical lattice,
      in the presence of atom-atom interactions. A new, interaction-induced Bloch
      period is identified. Analytical results are corroborated by realistic numerical
      calculations.

PMID- 12786553
TI  - Rotational spectrum and structure of Si3.
AB  - The rotational spectrum of a pure silicon cluster, the Si3 trimer, has been
      observed for the first time. From the rotational constants of the normal and the
      29Si and 30Si isotopic species, a precise geometrical structure has been derived:
      the trimer is an isosceles triangle with a bond to the apex Si of length 2.177(1)
      A and an apex angle of 78.10(3) degrees. The substantial inertial defect and
      fairly large centrifugal distortion suggest that the molecule possesses a shallow
      bending potential. Si3 is a good candidate for astronomical detection because
      radio lines of comparably massive silicon molecules (e.g., SiC2, SiC4, and SiS)
      are readily observed in at least one astronomical source. The rotational spectra
      of Si6, Si9, and even larger polar silicon clusters may be detectable with the
      present technique, as well as similar germanium clusters.

PMID- 12786554
TI  - Multiple paths to enhance optical transmission through a single subwavelength
      slit.
AB  - In this Letter, we explore transmission properties of a single subwavelength slit
      flanked by a finite array of grooves made on a thick metallic film. We identify
      three main mechanisms that can enhance optical transmission: groove cavity mode
      excitation (controlled by the depth of the grooves), in-phase groove reemission
      (controlled by the period of the groove array), and slit waveguide mode
      (controlled by the thickness of the metal film). By tuning these geometrical
      parameters, enhancements of transmission of light by up to 2 orders of magnitude
      can be achieved when all three mechanisms coincide. Experimental verification of
      these findings is also shown for structured silver films fabricated by focused
      ion-beam milling.

PMID- 12786555
TI  - Femtosecond phase-and-polarization control for background-free coherent anti
      Stokes Raman spectroscopy.
AB  - Phase-and-polarization coherent control is applied to control the nonlinear
      response of a quantum system. We use it to obtain high-resolution background-free
      single-pulse coherent anti-Stokes Raman spectra. The ability to control both the
      spectral phase and the spectral polarization enables measurement of a specific
      off-diagonal susceptibility tensor element while exploiting the different
      spectral response of the resonant Raman signal and the nonresonant background to
      achieve maximal background suppression.

PMID- 12786556
TI  - Rapid imbibition of fluids in carbon nanotubes.
AB  - Carbon nanotubes are potential building blocks for nanofluidic devices. The way
      fluids flow into and fill nanotubes is therefore of wide interest; however, there
      are currently no experimental data or theoretical models for this nanoscale
      process. We have carried out molecular dynamics simulations of nanotubes imbibing
      oil at an oil/vapor interface at 298 K. We find that nanotubes imbibe very
      rapidly (<or=445 m/s) via complex imbibition dynamics. The filling does not obey
      the macroscopic Washburn equation; the penetration length is a linear function of
      time.

PMID- 12786557
TI  - Shock-wave-induced jetting of micron-size bubbles.
AB  - Free gas bubbles in water with radii between 7 and 55 microm subjected to a shock
      wave exhibit a liquid jetting phenomenon with the jet pointing in the direction
      of the propagating shock wave. With increasing bubble radius, the length of the
      jet tip increases and a lower estimate of the averaged jet velocity increases
      linearly from 20 to 150 m/s. At a later stage, the jet breaks up and releases
      micron-size bubbles. In the course of shock wave permeabilization and
      transfection of biological cells, this observation suggests a microinjection
      mechanism when the cells are near bubbles exposed to a shock wave.

PMID- 12786558
TI  - Intermittency in the joint cascade of energy and helicity.
AB  - The statistics of the energy and helicity fluxes in isotropic turbulence are
      studied using high resolution direct numerical simulation. The scaling exponents
      of the energy flux agree with those of the transverse velocity structure
      functions through refined similarity hypothesis, consistent with Kraichnan's
      prediction. The helicity flux is even more intermittent than the energy flux.
      Consistent with this observation, the spatial helicity-flux structures are finer
      than those of energy flux and more tubelike in geometry.

PMID- 12786559
TI  - Plasma-wakefield acceleration of an intense positron beam.
AB  - Plasma wakefields are both excited and probed by propagating an intense 28.5 GeV
      positron beam through a 1.4 m long lithium plasma. The main body of the beam
      loses energy in exciting this wakefield while positrons in the back of the same
      beam can be accelerated by the same wakefield as it changes sign. The scaling of
      energy loss with plasma density as well as the energy gain seen at the highest
      plasma density is in excellent agreement with simulations.

PMID- 12786560
TI  - Numerical experiments on free-electron lasers without inversion.
AB  - The inversionless free-electron laser having a drift region consisting of two
      magnets is analyzed. Performing numerical simulations of electron motion inside
      wigglers and the drift region, we have shown that this system has a positive mean
      gain over the entire energy distribution of the electron beam. We study the
      influence of emittance and the spread of electron energies on the gain.

PMID- 12786561
TI  - Asymmetric self-phase modulation and compression of short laser pulses in plasma
      channels.
AB  - A relativistically intense femtosecond laser pulse propagating in a plasma
      channel undergoes dramatic photon deceleration while propagating a distance on
      the order of a dephasing length. The deceleration of photons is localized to the
      back of the pulse and is accompanied by compression and explosive growth of the
      ponderomotive potential. Fully explicit particle-in-cell simulations are applied
      to the problem and are compared with ponderomotive guiding center simulations. A
      numerical Wigner transform is used to examine local frequency shifts within the
      pulse and to suggest an experimental diagnostic of plasma waves inside a
      capillary.

PMID- 12786562
TI  - Experimental identification of the kink instability as a poloidal flux
      amplification mechanism for coaxial gun spheromak formation.
AB  - The magnetohydrodynamic kink instability is observed and identified
      experimentally as a poloidal flux amplification mechanism for coaxial gun
      spheromak formation. Plasmas in this experiment fall into three distinct regimes
      which depend on the peak gun current to magnetic flux ratio, with (I) low values
      resulting in a straight plasma column with helical magnetic field, (II)
      intermediate values leading to kinking of the column axis, and (III) high values
      leading immediately to a detached plasma. Onset of column kinking agrees
      quantitatively with the Kruskal-Shafranov limit, and the kink acts as a dynamo
      which converts toroidal to poloidal flux. Regime II clearly leads to both
      poloidal flux amplification and the development of a spheromak configuration.

PMID- 12786563
TI  - Observation of novel liquid-crystalline phase above the bulk-melting temperature.
AB  - In this paper, we show that a noncrystalline but ordered smectic-like phase
      exists above the bulk-melting temperature (T(m)) at poly(n-alkyl acrylates)-air
      interface. The surface ordered phase is one monolayer thick and undergoes a sharp
      transition from order to disorder 10 degrees C above T(m) for n=22. The presence
      of a surface phase that does not exist in the bulk has important implications in
      the design of thermally responsive adhesives.

PMID- 12786564
TI  - Complete identification of alkali sites in ion conducting lithium silicate
      glasses: a computer study of ion dynamics.
AB  - The available sites for ions in a typical disordered ionic conductor are
      determined. For this purpose we devised a straightforward algorithm which via
      cluster analysis identifies these sites from long time ionic trajectories below
      the glass transition. This is exemplified for a lithium silicate glass
      (Li2O)(x)(SiO2)((1-x)) for x=0.5 and x=0.1. We find for both concentrations that
      the number of sites is only slightly bigger than the number of ions. This result
      suggests a theoretical description of the dynamics in terms of mobile vacancies
      as most appropriate. Furthermore, identification of the ionic sites allows one to
      obtain detailed characteristics of the ionic motion, e.g., quantification of
      correlated forward-backward jumps.

PMID- 12786565
TI  - X-ray synchrotron study of liquid-vapor interfaces at short length scales: effect
      of long-range forces and bending energies.
AB  - We have investigated the small-scale structure of the liquid-vapor interface
      using synchrotron x-ray scattering for liquids with different molecular
      structures and interactions. The effective momentum-dependent surface energy
      first decreases from its macroscopic value due to the effect of long-range
      forces, and then increases with increasing wave vector. The results are analyzed
      using a recent density functional theory. The large wave-vector increase is
      attributed to a bending energy for which local and nonlocal contributions are
      equally important.

PMID- 12786566
TI  - General model for water monomer adsorption on close-packed transition and noble
      metal surfaces.
AB  - Ab initio density functional theory has been used to investigate the adsorption
      of H2O on several close-packed transition and noble metal surfaces. A remarkably
      common binding mechanism has been identified. On every surface H2O binds
      preferentially at an atop adsorption site with the molecular dipole plane nearly
      parallel to the surface. This binding mode favors interaction of the H2O 1b(1)
      delocalized molecular orbital with surface wave functions.

PMID- 12786567
TI  - Neutron diffraction study of the size-induced tetragonal to monoclinic phase
      transition in zirconia nanocrystals.
AB  - Accurate neutron powder diffraction experiments at several temperatures allow one
      to monitor the reconstructive tetragonal to monoclinic phase transition as a
      function of the size of zirconia nanoparticles. The structure of the tetragonal
      phase observed in the nanocrystals is identical to that observed in micrometric
      zirconia above 1400 K. A uniaxial strain depending on grain size is observed. The
      phase transition occurs above a threshold crystal size. These results are
      analyzed within the Landau theory and can be understood as a mechanism of size
      dependent phase transition where the primary order parameter is altered by the
      nanoparticle size.

PMID- 12786568
TI  - Morphological and compositional evolution of the ge/si(001) surface during
      exposure to a si flux.
AB  - By using scanning tunneling microscopy we found that the surface reconstruction
      of Ge/Si(001) epilayers evolves from (M x N) to (2 x N), and eventually to (2 x
      1), during exposure to a Si flux. This sequence appears to be just the inverse of
      that observed during the growth of Ge or SiGe alloys on Si(001). However,
      molecular dynamics simulations supported by ab initio calculations allow us to
      interpret this morphological evolution in terms of Si migration through the
      epilayer and complex Si-Ge intermixing below the top Ge layer.

PMID- 12786569
TI  - Layer spacings in coherently strained epitaxial metal films.
AB  - Laterally resolved measurements of the quantum size effect (QSE) in electron
      reflectivity are made with low energy electron microscopy on coherently strained
      Ag films on a W(110) surface. The evolution of the total film thickness with
      increasing number of atomic layers is determined accurately by dynamical theory
      analysis of the QSE features. Combined with a model of layer spacings obtained
      from first-principles calculations, this provides for a novel approach to
      determine the buried interface layer spacing, which is inaccessible to other
      methods.

PMID- 12786570
TI  - "Devil's staircase" in Pb/Si(111) ordered phases.
AB  - With scanning tunneling microscopy we have found that ordered phases in
      Pb/Si(111) are one of the best examples of the "devil's staircase" phase diagram.
      Phases within a narrow coverage range (1.2<theta<1.3 monolayers) are constructed
      with the rules similar to the ones found in theoretical models.

PMID- 12786571
TI  - Direct observation of localized defect States in semiconductor nanotube
      junctions.
AB  - We report scanning tunneling microscopy of semiconductor-semiconductor carbon
      nanotube junctions with different band gaps. Characteristic features of the wave
      functions at different energy levels, such as a localized defect state, are
      clearly exhibited in the atomically resolved scanning tunneling spectroscopy. The
      peaks of the Van Hove singularity on each side penetrate and decay into the
      opposite side across the junction over a distance of approximately 2 nm. These
      experimental features are accounted for, with the help of tight-binding
      calculation, by the presence of pentagon-heptagon pair defects at the junction.

PMID- 12786572
TI  - Polar oxide interface stabilization by formation of metallic nanocrystals.
AB  - In situ x-ray photoelectron spectroscopy and ex situ transmission electron
      microscopy and diffraction studies of a model Fe3O4(111)/MgO(111) polar oxide
      interface exclude stabilization by interface faceting, reconstruction, or by
      formation of a continuous interfacial layer with altered stoichiometry, and
      uncover stabilization by dominant formation of metallic Fe(110) nanocrystals. The
      iron nanocrystals nucleate both at the interface and within the magnetite film
      and grow in a Nishiyama-Wasserman orientation relationship with a bimodal size
      distribution related to twinning. Minority magnetite nanocrystals were also
      observed, growing in the less polar (100) orientation than the magnetite (111)
      film. Electron transfer and bond hybridization mechanisms are likely at the
      metal/oxide and oxide/oxide interfaces and remain to be explored.

PMID- 12786573
TI  - Atomic-scale observation of temperature and pressure driven preroughening and
      roughening.
AB  - Preroughening and roughening transitions are observed on the GaAs(001) surface
      using scanning tunneling microscopy. By tuning the substrate temperature or As4
      pressure the surface morphology can be made free of islands, covered with one
      monolayer high islands or covered with islands on top of islands forming a
      wedding-cake-type structure. These three distinct surface morphologies are
      classified as ordered flat (OF), disordered flat (DOF), and rough within the
      restricted solid-on-solid model. Here, the DOF phase is macroscopically flat;
      however, an up-down-up-down step pattern persists across the entire surface.
      Using this model we have determined the next-nearest-neighbor interaction energy
      to be about 0.05 eV.

PMID- 12786574
TI  - Atomic engineering of photon emission with a scanning tunneling microscope.
AB  - We present measurements of photon emission from individual several-atom silver
      chains on the NiAl(110) surface, excited by tunneling electrons in a scanning
      tunneling microscope (STM). The chains were assembled by manipulating single
      silver atoms on the NiAl(110) surface with the STM. The photon energy of this
      emission can be tuned by appending a single atom to the chain. These changes in
      photon emission result from changes in the electronic structure of the silver
      chain, each electronic state inside the chain being associated with a distinct
      channel of emission.

PMID- 12786575
TI  - Antiholons in one-dimensional t-J models.
AB  - Using a newly developed hybrid Monte Carlo algorithm for the nearest-neighbor
      (nn) t-J model, we show that antiholons identified in the supersymmetric inverse
      squared (IS) t-J model are clearly visible in the electron-addition spectrum of
      the nn t-J model at J=2t and also for J=0.5t, a value of experimental relevance.

PMID- 12786576
TI  - Robust ab initio calculation of condensed matter: transparent convergence through
      semicardinal multiresolution analysis.
AB  - We present the first wavelet-based all-electron density-functional calculations
      to include gradient corrections and the first in a solid. Direct comparison shows
      this approach to be unique in providing systematic "transparent" convergence,
      convergence with a priori prediction of errors, to beyond chemical (millihartree)
      accuracy. The method is ideal both for exploration of materials under novel
      conditions where there is little experience with how traditional methods perform
      and for the development and use of chemically accurate density functionals, which
      demand access to such precision.

PMID- 12786577
TI  - Fractionalized fermi liquids.
AB  - In spatial dimensions d>or=2, Kondo lattice models of conduction and local moment
      electrons can exhibit a fractionalized, nonmagnetic state (FL(*)) with a Fermi
      surface of sharp electronlike quasiparticles, enclosing a volume quantized by
      (rho(a)-1)(mod 2), with rho(a) the mean number of all electrons per unit cell of
      the ground state. Such states have fractionalized excitations linked to the
      deconfined phase of a gauge theory. Confinement leads to a conventional Fermi
      liquid state, with a Fermi volume quantized by rho(a)(mod 2), and an intermediate
      superconducting state for the Z2 gauge case. The FL(*) state permits a second
      order metamagnetic transition in an applied magnetic field.

PMID- 12786578
TI  - Direct observation of optically injected spin-polarized currents in
      semiconductors.
AB  - Quantum interference of one- and two-photon excitation of unbiased semiconductors
      yields ballistic currents of carriers. The magnitudes and directions of the
      currents and the spin orientations of the carriers are controlled by the
      polarization and relative phase of the exciting femtosecond laser fields. We
      provide direct experimental evidence for the spin polarization of the optically
      injected spin currents by detecting a phase-dependent spatial shift of the
      circularly polarized photoluminescence in cubic ZnSe.

PMID- 12786579
TI  - Transport through quantum dots in mesoscopic circuits.
AB  - We study the transport through a quantum dot, in the Kondo Coulomb blockade
      valley, embedded in a mesoscopic device with finite wires. The quantization of
      states in the circuit that hosts the quantum dot gives rise to finite size
      effects. These effects make the conductance sensitive to the ratio of the Kondo
      screening length to the wires length and provide a way of measuring the Kondo
      cloud. We present results obtained with the numerical renormalization group for a
      wide range of physically accessible parameters.

PMID- 12786580
TI  - Lorenz number in high T(c) superconductors: evidence for bipolarons.
AB  - The strong electron-phonon interaction in cuprates has gathered support over the
      last decade in a number of experiments. While phonons remain almost
      unrenormalized, electrons are transformed into itinerant bipolarons and thermally
      excited polarons when the electron-phonon interaction is strong. We calculate the
      Lorenz number of the system to show that the Wiedemann-Franz law breaks down
      because of the interference of polaron and bipolaron contributions in the heat
      flow. The model fits numerically the experimental Hall Lorenz number, which
      provides direct evidence for bipolarons in the cuprates.

PMID- 12786581
TI  - BCS-like Bogoliubov quasiparticles in high-T(c) superconductors observed by angle
      resolved photoemission spectroscopy.
AB  - We performed high-resolution angle-resolved photoemission spectroscopy on triple
      layered high-T(c) cuprate Bi(2)Sr(2)Ca(2)Cu(3)O(10+delta). We have observed the
      full energy dispersion (electron and hole branches) of Bogoliubov quasiparticles
      and determined the coherence factors above and below E(F) as a function of
      momentum from the spectral intensity as well as from the energy dispersion based
      on BCS theory. The good quantitative agreement between the experiment and the
      theoretical prediction suggests the basic validity of BCS formalism in describing
      the superconducting state of cuprates.

PMID- 12786582
TI  - Mirror domain structures induced by interlayer magnetic wall coupling.
AB  - We have found that during giant magnetoresistance measurements in approximately
      10 x 10 mm(2) NiFe/Cu/Co continuous film spin-valve structures, the resistance
      value suddenly drops to its absolute minimum during the NiFe reversal. The
      results reveal that the alignment of all magnetic domains in the NiFe film follow
      exactly that of corresponding domains in the Co film for an appropriate applied
      field strength. This phenomenon is caused by trapping of the NiFe domain walls
      through the magnetostatic interaction with the Co domain-wall stray fields.
      Consequently, the interlayer domain-wall coupling induces a mirror domain
      structure in the magnetic trilayer.

PMID- 12786583
TI  - Quantum and thermal fluctuations in the SU(N) Heisenberg spin-glass model near
      the quantum critical point.
AB  - We solve for the SU(N) Heisenberg spin glass in the limit of large N focusing on
      small S and T. We study the effect of quantum and thermal fluctuations in the
      frequency dependent response function and observe interesting transfers of
      spectral weight. We compute the T dependence of the order parameter and the
      specific heat and find an unusual T2 behavior for the latter at low temperatures
      in the spin-glass phase. We find remarkable qualitative agreement with various
      experiments on the quantum frustrated magnet SrCr(9p)Ga(12-9p)O19.

PMID- 12786584
TI  - Temperature dependence of the surface anisotropy of Fe ultrathin films on
      Cu(001).
AB  - We report an experimental approach to separate temperature dependent reversible
      and irreversible contributions to the perpendicular magnetic anisotropy of Fe
      films grown at low temperatures on Cu(001) substrates. The surface anisotropy
      K(S)(T) is found to decrease linearly with temperature, causing a thermally
      induced spin reorientation into the plane. The irreversible shift of the spin
      reorientation transition and the coercivity of the iron films are directly
      correlated to the increasing Fe island size during annealing. The increased
      coercivity is discussed in terms of domain wall energy inhomogeneities provided
      by the islands.

PMID- 12786585
TI  - Definitive spectroscopic determination of the transverse interactions responsible
      for the magnetic quantum tunneling in Mn(12)-acetate.
AB  - We present detailed angle-dependent single crystal electron paramagnetic
      resonance (EPR) data for field rotations in the hard plane of the S=10 single
      molecule magnet Mn(12)-acetate. A clear fourfold variation in the resonance
      positions may be attributed to an intrinsic fourth-order transverse anisotropy
      (O(4)/(4)). Meanwhile, a fourfold variation of the EPR line shapes confirms a
      recently proposed model wherein disorder associated with the acetic acid of
      crystallization induces a locally varying quadratic (rhombic) transverse
      anisotropy [O (2)/(2) identical with E(S (2)/(x)-S(2)/(y))]. These findings
      explain most aspects of the magnetic quantum tunneling observed in Mn(12)
      acetate.

PMID- 12786586
TI  - Bright band gap photoluminescence from unprocessed single-walled carbon
      nanotubes.
AB  - Unprocessed single-walled carbon nanotubes suspended in air at room temperature
      emit bright, sharply peaked band gap photoluminescence. This is in contrast with
      measurements taken from nanotubes lying on the flat surface for which no
      luminescence was detected. Each individual nanotube has a luminescence peak of
      similar linewidth ( approximately 13 meV), with different species emitting at
      various different wavelengths spanning at least 1.0 to 1.6 microm. A strong
      enhancement of photoluminescence intensity is observed when the excitation
      wavelength is resonant with the second Van Hove singularity, unambiguously
      confirming the origin of the photoluminescence.

PMID- 12786587
TI  - Multichannel mueller matrix ellipsometry for simultaneous real-time measurement
      of bulk isotropic and surface anisotropic complex dielectric functions of
      semiconductors.
AB  - We have applied a dual rotating-compensator multichannel ellipsometer to acquire
      spectra ( approximately 2.0-4.6 eV) in all 16 elements of the Mueller matrix
      associated with a specularly reflecting surface, in a minimum time of 0.25 s. In
      this initial study, such results have been collected for the (110) silicon
      surface at an incidence angle of approximately 70 degrees and have been used to
      derive spectra in the bulk isotropic dielectric function epsilon (b)= epsilon
      (1b)-i epsilon (2b) and the surface-induced dielectric function anisotropy Delta
      epsilon =Delta epsilon (1)-iDelta epsilon (2). Thus, this instrument shows
      promise for simultaneous real-time measurement of epsilon (b) and Delta epsilon
      spectra in oblique reflection during the fabrication of semiconductor structures
      having bulk isotropic components.

PMID- 12786588
TI  - Nonlinear magneto-optical kerr rotation of an oxide superlattice with
      artificially broken symmetry.
AB  - Simultaneously broken time-reversal and spatial-inversion symmetries can be
      realized in the epitaxially grown oxide "tricolor" superlattices composed of
      three sequential kinds of perovskite layers including a ferromagnetic one
      (manganese oxide). As a generic feature of such a system, the magnetic-field
      induced second-harmonic generation and the resultant Kerr rotation of second
      harmonic light were demonstrated. The signal intensity probes the interface
      magnetization of the superlattice, where temperature variation is shown to be
      distinct from the bulk feature.

PMID- 12786589
TI  - Evidence for third-harmonic generation in disguise of second-harmonic generation
      in extreme nonlinear optics.
AB  - In contrast with traditional nonlinear optics, a peak at the spectral position of
      the second harmonic of a laser can also be generated in an inversion-symmetric
      medium in the regime of extreme nonlinear optics. We describe the underlying
      mechanism of such third-harmonic generation in disguise of second-harmonic
      generation and compare theory with the optical as well as the radio-frequency
      spectra measured in recent experiments on thin ZnO films. The peak at twice the
      carrier-envelope offset frequency in the radio-frequency spectra is shown to be
      an unambiguous signature of such a process.

PMID- 12786590
TI  - Exchange coupling in P(VDF-TrFE) copolymer based all-organic composites with
      giant electrostriction.
AB  - In this Letter, we discuss the dramatically enhanced electrostriction and
      dielectric constant in an all-organic composite consisting of polyvinylidene
      fluoride trifluoroethylene [P(VDF-TrFE)] copolymer matrix and copper
      phthalocyanine (CuPc) particles, which could not be explained by traditional
      composite theory. Using a Landau-type potential energy combined with energy
      minimization, we demonstrate that the dramatic property enhancement is due to the
      exchange coupling between the dielectrically hard P(VDF-TrFE) and dielectrically
      soft CuPc, which becomes dominant when the heterogeneity size of the composite is
      comparable to the exchange length. The exchange coupling is a very effective
      mechanism for the enhancement of functional properties in ferroelectric and
      dielectric systems, and its variation with various material parameters is
      demonstrated and discussed.

PMID- 12786591
TI  - Quantum logic gates for hot ions without a speed limitation.
AB  - We propose a scheme for realizing two-qubit quantum phase gates with trapped ions
      in thermal motion. In the scheme, the ions are simultaneously illuminated by a
      standing-wave laser tuned to the carrier, which virtually excites several
      vibrational modes. The scheme puts no limitations on the intensity of the laser
      field, allowing the production of a quantum logic gate for hot ions with an
      arbitrarily high speed as long as a laser field of sufficiently high intensity is
      available.

PMID- 12786592
TI  - Entangling distant atoms by interference of polarized photons.
AB  - We propose a scheme to generate the entangled state of two Lambda-type three
      level atoms trapped in distant cavities by using interference of polarized
      photons. Two possible spontaneous emission channels of each excited atom result
      in a coherent superposition of the states of two atoms. The subsequent detection
      of the different polarized photons reveals that both atoms are in different
      ground states, but an interference effect prevents us from distinguishing which
      atom is in which ground state; the atoms are thus entangled. In comparison with
      the original proposal of interference-induced entanglement [C. Cabrillo, J.
      Cirac, P. Garcia-Fernandez, and P. Zoller, Phys. Rev. A 59, 1025 (1999)]], in our
      scheme the weakly driven condition is not required, and the influence of atomic
      excitement and atomic recoil on the entanglement fidelity can be eliminated.

PMID- 12786593
TI  - Structural determinant of protein designability.
AB  - Here we present an approximate analytical theory for the relationship between a
      protein structure's contact matrix and the shape of its energy spectrum in amino
      acid sequence space. We demonstrate a dependence of the number of sequences of
      low energy in a structure on the eigenvalues of the structure's contact matrix,
      and then use a Monte Carlo simulation to test the applicability of this
      analytical result to cubic lattice proteins. We find that the lattice structures
      with the most low-energy sequences are the same as those predicted by the theory.
      We argue that, given sufficiently strict requirements for foldability, these
      structures are the most designable, and we propose a simple means to test whether
      the results in this paper hold true for real proteins.

PMID- 12786594
TI  - Natural thermoelectric heat pump in social wasps.
AB  - Photographs of wasps or hornets, taken with different temperature sensitive
      infrared cameras, reveal body temperatures that are sometimes significantly lower
      than the ambient temperature. This suggests that the hornets possess an intrinsic
      biological heat pump mechanism which can be used to achieve such cooling.
      Evidence is presented to substantiate this novel suggestion and to argue that the
      heat pump is most likely implemented by exploiting a thermoelectric effect in the
      hornet cuticle. Such a natural heat pump can conceivably also serve to cool the
      active hornet, engaged in daytime activities outside the nest at ambient
      temperatures exceeding 40 degrees C, to a body temperature that is low enough to
      allow its survival in extreme thermal conditions. It might also function as a
      means of raising the body temperature up to a level that enables the hornet to
      remain active even when the ambient temperature is as low as 10 degrees C.

PMID- 12786595
TI  - Behavioral stochastic resonance within the human brain.
AB  - We provide the first evidence that stochastic resonance within the human brain
      can enhance behavioral responses to weak sensory inputs. We asked subjects to
      adjust handgrip force to a slowly changing, subthreshold gray level signal
      presented to their right eye. Behavioral responses were optimized by presenting
      randomly changing gray levels separately to the left eye. The results indicate
      that observed behavioral stochastic resonance was mediated by neural activity
      within the human brain where the information from both eyes converges.

PMID- 12786596
TI  - Dynamics of large semiflexible chains probed by fluorescence correlation
      spectroscopy.
AB  - Fluorescence correlation spectroscopy was used to probe the dynamics of lambda
      phage DNA in aqueous solution labeled with the randomly intercalating dye TOTO.
      The linear macromolecules (i). carry more than one chromophore and (ii). are
      larger than the waist of the focal volume. The correlation function decays
      significantly faster than expected for a stiff globule of corresponding size but
      is in good agreement with the dynamic model of semiflexible chains including
      hydrodynamic interactions. As the chromophore density is lowered the correlation
      time decreases in accordance with this model.

PMID- 12786597
TI  - Comment on "dynamical foundations of nonextensive statistical mechanics".

PMID- 12786599
TI  - Comment on "investigation of the correlation potential from Kohn-Sham
      perturbation theory".

PMID- 12786601
TI  - Distinct regulation of cytosolic phospholipase A2 phosphorylation, translocation,
      proteolysis and activation by tumour necrosis factor-receptor subtypes.
AB  - The hormonally regulated Ca(2+)-dependent enzyme, cytosolic phospholipase A(2)
      (cPLA(2)) is activated by a range of inflammatory stimuli. Tumour necrosis factor
      alpha (TNF) is one of the first known stimuli for cPLA(2) but it is not known
      whether both TNF receptor subtypes are involved in activating the lipase. In the
      present study, we show for the first time that both type I 55 kDa TNFR (TNFR1)
      and type II 75 kDa TNFR (TNFR2) stimulate cPLA(2) enzyme, but with distinct
      signalling mechanisms. TNFR1 activates mitogen-activated protein kinase (MAPK)
      and p38MAPK. TNFR1 then phosphorylates and activates cPLA(2) in a MAPK-dependent
      fashion. Furthermore, TNFR1 causes the translocation and caspase-dependent
      proteolysis of cPLA(2) as part of its activation profile. TNFR2, on the other
      hand, does not cause the phosphorylation of cPLA(2) as it does not activate MAPK
      or p38MAPK, but instead activates cPLA(2) by causing its translocation to plasma
      membrane and perinuclear subcellular regions. TNFR2 activation causes a delayed,
      slight increase in [Ca(2+)](i) of <50 nM that may contribute towards the
      translocation and activation of cPLA(2). Therefore both TNF receptor subtypes
      play a role in cPLA(2) activation, but by means of separate signal-transduction
      pathways.

PMID- 12786602
TI  - dDYRK2: a novel dual-specificity tyrosine-phosphorylation-regulated kinase in
      Drosophila.
AB  - Dual-specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are an
      emerging family of protein kinases that have been identified in all eukaryotic
      organisms examined to date. DYRK family members are involved in regulating key
      developmental and cellular processes such as neurogenesis, cell proliferation,
      cytokinesis and cellular differentiation. Two distinct subgroups exist, nuclear
      and cytosolic. In Drosophila, the founding family member minibrain, whose human
      orthologue maps to the Down syndrome critical region, belongs to the nuclear
      subclass and affects post-embryonic neurogenesis. In the present paper, we report
      the isolation of dDYRK2, a cytosolic DYRK and the putative product of the smell
      impaired smi35A gene. This is the second such kinase described in Drosophila, but
      the first to be characterized at the molecular and biochemical level. dDYRK2 is
      an 81 kDa dual-specificity kinase that autophosphorylates on tyrosine and
      serine/threonine residues, but appears to phosphorylate exogenous substrates only
      on serine/threonine residues. It contains a YXY motif in the activation loop of
      the kinase domain in the same location as the TXY motif in mitogen-activated
      protein kinases. dDYRK2 is tyrosine-phosphorylated in vivo, and mutational
      analysis reveals that the activation loop tyrosines are phosphorylated and are
      essential for kinase activity. Finally, dDYRK2 is active at all stages of fly
      development, with elevated levels observed during embryogenesis and pupation.

PMID- 12786603
TI  - Comparative thermal denaturation of Thermus aquaticus and Escherichia coli type 1
      DNA polymerases.
AB  - Thermal denaturations of the type 1 DNA polymerases from Thermus aquaticus (Taq
      polymerase) and Escherichia coli (Pol 1) have been examined using differential
      scanning calorimetry and CD spectroscopy. The full-length proteins are single
      polypeptide chains comprising a polymerase domain, a proofreading domain
      (inactive in Taq) and a 5' nuclease domain. Removal of the 5' nuclease domains
      produces the 'large fragment' domains of Pol 1 and Taq, termed Klenow and Klentaq
      respectively. Although the high temperature stability of Taq polymerase is well
      known, its thermal denaturation has never been directly examined previously.
      Thermal denaturations of both species of polymerase are irreversible, precluding
      rigorous thermodynamic analysis. However, the comparative melting behaviour of
      the polymerases yields information regarding domain structure, domain
      interactions and also the similarities and differences in the stabilizing forces
      for the two species of polymerase. In differential scanning calorimetry, Klenow
      and Klentaq denature as single peaks, with a melting temperature T(m) of 37 and
      100 degrees C respectively at pH 9.5. Both full-length polymerases are found to
      be comprised of two thermodynamic unfolding domains with the 5' nuclease domains
      of each melting separately. The 5' nuclease domain of Taq denatures as a separate
      peak, 10 degrees C before the Klentaq domain. Melting of the 5' nuclease domain
      of Pol 1 overlaps with the Klenow fragment. Presence of the 5' nuclease domain
      stabilizes the large fragment in Pol 1, but destabilizes it in Taq. Both Klentaq
      and Klenow denaturations have a very similar dependence on pH and methanol,
      indicating similarities in the hydrophobic forces and protonation effects
      stabilizing the proteins. Melting monitored by CD yields slightly lower T(m)
      values, but almost identical van't Hoff enthalpy Delta H values, consistent with
      two-state unfolding followed by an irreversible kinetic step. Analysis of the
      denaturation scan rate dependences with Arrhenius formalism estimates a kinetic
      barrier to irreversible denaturation for Klentaq that is significantly higher
      than that for Klenow.

PMID- 12786605
TI  - Review article: diagnosis, monitoring and treatment of distal colitis.
AB  - The diagnostic work-up of ulcerative colitis at presentation is based on the
      collection of clinical, microbiological, radiological, endoscopic and histologic
      data. Serological markers are characterized by too low a sensitivity to be
      commonly utilized in clinical practice. Although endoscopic and histologic
      features are characterized by very high sensitivity and specificity for the
      diagnosis of ulcerative colitis, negative stool cultures and parasites are
      mandatory to exclude an infectious aetiology at presentation. The treatment of
      choice of an acute flare-up of distal ulcerative colitis is represented by oral
      or topical mesalazine, or a combination of both, whereas the use of topical or
      systemic steroids should be restricted to patients who prove to be refractory to
      first-line treatments. Preliminary data suggest that the achievement of
      endoscopic and histologic remission after an acute flare of the disease might be
      associated with a prolonged remission.

PMID- 12786606
TI  - Review article: medical treatment of severe ulcerative colitis.
AB  - Severe colitis is a life-threatening complication of ulcerative colitis. Early
      recognition of the severity of the colitis and intensive treatment and monitoring
      have all contributed to improved outcome. Since their introduction in 1950s,
      corticosteroids are the first line therapy for severe active ulcerative colitis
      (UC). Several prognostic parameters (such as stools movement per day, C-reactive
      protein, increased amount of intestinal gas or small bowel dilation,
      hypoalbuminemia, fever etc) help the physician to quickly introduce cyclosporin
      or to refer the patient to the surgeon. This decision requires a careful
      evaluation of the patient and a medical /surgical team. Infliximab seems to be a
      promising drug but more controlled trial are needed.

PMID- 12786607
TI  - Review article: Crohn's disease: monitoring disease activity.
AB  - A global measurement of Crohn's disease activity, comprising clinical,
      endoscopic, biochemical and pathological features is not available yet and
      perhaps is unobtainable. In this review we analyse the most used and validated
      clinical indices (Crohn's Disease Activity Index [CDAI], Perianal Disease
      Activity Index [PDAI], fistula drainage assessment), quality of life scores
      (Inflammatory Bowel Disease Questionnaire [IBDQ]), sub-clinical markers (C
      reactive protein, faecal calprotectin, intestinal permeability) and endoscopic
      indices (Crohn's Disease Endoscopic Index of Severity [CDEIS]/Simple Endoscopic
      Score for Crohn's Disease [SES-CD], Rutgeeerts' score for postsurgical
      recurrence). We also review the main advantages and disadvantages of each of
      these scoring systems. All these indices are rather complex and time-consuming,
      therefore their use is limited to clinical trials. In everyday clinical practice
      most gastroenterologists rely on their global clinical judgement, which is less
      reproducible, but simpler for decision-making.

PMID- 12786608
TI  - Review article: medical treatment of mild to moderately active Crohn's disease.
AB  - Crohn's disease is a chronic, debilitating subset of inflammatory bowel diseases,
      which may affect any part of the gastrointestinal tract. The most common sites of
      inflammation are the terminal ileum and/or the colon. Fistulous disease is
      present in up to 20% of patients, particularly in those having rectal
      involvement. The aetiology of Crohn's disease still remains obscure, therefore
      medical therapy is directed towards symptomatic relief in active disease and
      relapse prevention in the long-term setting. Contemporary Crohn's disease
      management comprises individual treatment depending mainly on Crohn's disease
      localization in the gastrointestinal tract and the disease severity. The mainstay
      of current medical treatment for mild to moderately active stages of Crohn's
      disease includes aminosalicylates, antibiotics, glucococorticosteroids and
      immunomodulators. Biologics such as anti TNF-compounds and anti-integrins are
      being introduced.

PMID- 12786609
TI  - Review article: medical treatment of moderate to severe Crohn's disease.
AB  - The treatment for patients with Crohn's disease of moderate to severe activity
      includes traditional drugs, such as corticosteroids, the primary therapy for
      these forms of disease, able to induce the remission of symptoms in a high
      percentage of patients. Because of the side-effects produced by systemic
      steroids, a new glucocorticoid derivative, budesonide, which acts locally in the
      mucosa, has recently been introduced with positive results. On the assumption
      that intestinal bacteria play a role in the causing Crohn's disease symptoms,
      antibiotics are often used in the treatment of active phases, as an alternative
      to or in association with steroids. The most widely employed antibiotics are
      metronidazole and ciprofloxacin. Immunosuppressors, such as azathioprine and 6
      mercaptopurine, are useful for the treatment of chronic active disease and for
      maintaining remission, but they have only a marginal role in the therapy of an
      acute flare-up of Crohn's disease. Methotrexate acts more rapidly and its use in
      patients with active disease resistant to standard therapy is of interest. The
      discovery of biological agents represents a new era in the management of
      patients. To date, infliximab is the more extensively studied biological therapy
      in the treatment of Crohn's disease and clinical studies have demonstrated its
      efficacy in inducing remission of refractory disease.

PMID- 12786610
TI  - Review article: maintenance treatment of Crohn's disease.
AB  - The aetiology of Crohn's disease is unknown and therefore no curative treatments
      are available for the disease. The natural history of Crohn's disease is
      characterized by recurrent flare-ups of symptoms. Several drug treatments are
      effective in inducing clinical remission. However, no drug treatments are
      available in order to prevent clinical relapses, although several drug regimens
      may delay clinical flare-ups. Crohn's disease treatment for maintaining clinical
      remission needs to be tailored in relation to specific characteristics of each
      patient. The frequency of clinical relapse indeed shows marked variations in
      subgroups of patients, as the likelyhood of relapse is higher in patients in
      clinical remission for less than 6 months. Treatment strategies for maintaining
      remission may therefore differ among inactive patients. In chronically active,
      steroid-dependent or steroid-refractory Crohn's disease patients immunomodulatory
      drugs (azathioprine 2-2.5 mg/kg by mouth, 6-mercaptopurine 1-1.5 mg/kg by mouth,
      or methotrexate 15-25 mg/i.m./week) should be added to oral mesalazine (2.4
      g/day), while in long-term inactive Crohn's disease patients mesalazine alone may
      be effective in delaying relapse. Recently, treatment with anti-tumour necrosis
      factor-alpha monoclonal antibodies (Infliximab or CDP571) has shown efficacy in
      delaying relapse in responsive patients. One other issue which needs to be
      considered before selecting drug treatments for maintaining remission in Crohn's
      disease, is that Crohn's disease activity is currently assessed on the basis of
      standard clinical scores which may not appropriately reflect the biological
      activity of the disease. Clinical remission as defined by standardized scores may
      include heterogeneous subgroups of patients showing different endoscopic and
      histological activity or persistence of activated immunocompetent cells within
      the gut. Several sub-clinical markers of relapse have indeed been reported in
      quiescent Crohn's disease, although their usefulness in clinical practice in
      currently uncertain.

PMID- 12786611
TI  - Review article: prevention of postsurgical relapse and recurrence in Crohn's
      disease.
AB  - After first resection in Crohn's disease at 1 year 60-80% of patients have
      endoscopic recurrence, 10-20% have clinical relapse, and 5% have surgical
      recurrence.1, 2 This review focuses on the actual evidence on the prevention of
      recurrence and relapse dealing with risk factors and with drugs. Smoking is the
      only risk factor for Crohn's disease, that has been shown to be related to both
      endoscopic and surgical recurrence and relapse. Among the different drugs
      evaluated, some (Mesalamine and Metronidazole) have been shown to be effective,
      whereas others (immunosuppressive) need to be evaluated in further, new trials.

PMID- 12786612
TI  - New developments in the pathophysiology of gastro-oesophageal reflux disease
      (GERD): implications for patient management.
AB  - The spectrum of gastro-oesophageal reflux disease (GERD) has expanded; indeed the
      majority of individuals with symptomatic GERD do not have erosive reflux disease
      (ERD); this group has been referred to as nonerosive or negative-endoscopy reflux
      disease (NERD). There may be important differences between NERD and ERD in terms
      of pathophysiology and management. Thus, NERD patients appear relatively
      resistant to proton pump inhibitors and may not be good surgical candidates. The
      clinician caring for patients with GERD must therefore be aware of the full
      spectrum of GERD and of the pathophysiological and therapeutic implications of
      NERD. Recent twin studies have revealed that genetic factors play a role in GERD
      and form the basis for future studies on the role of inheritance in the various
      manifestations of GERD. Several recent investigations have reaffirmed the primacy
      of acid reflux in the pathogenesis of GERD and have also provided insights into
      the pathophysiology of postprandial heartburn. Transient lower oesophageal
      sphincter relaxations and hiatal hernias have emerged as major and interacting
      factors in the genesis of reflux events and in the potentiation of acid exposure;
      the former are attracting considerable attention as a potential therapeutic
      target. Nocturnal acid breakthrough, which has been implicated in the failure of
      some patients to respond to high doses of proton pump inhibitors, appears, on
      further examination, to be a gastric rather than an oesophageal phenomenon, and
      may not be of clinical or therapeutic importance.

PMID- 12786613
TI  - Review article: management of mild and severe gastro-oesophageal reflux disease.
AB  - Treatment of endosocopy-negative gastro-oesophageal reflux disease (s-GERD)
      should be directed towards rapid relief of symptoms and then maintenance of
      relief using minimum yet effective therapy. Responses to proton pump inhibitors
      are somewhat lower in s-GERD patients compared to GERD with overt erosive damage
      (e-GERD). The reasons for a lower response rate are not clear but may relate to
      the inclusion of patients who do not have reflux disease or patients with a lower
      oesophageal sensory threshold. Also poorly understood is the lower yield of
      complete heartburn relief when the number of associated dyspeptic symptoms is
      high. Some form of long-term therapy is needed in the majority of patients. 'On
      demand' proton pump inhibitor therapy to control reflux symptoms is a new and
      attractive option. Time to study discontinuation due to insufficient control of
      heartburn, or any other reason resulting in unwillingness to continue with on
      demand therapy, is a pragmatic outcome that is well suited to definition of the
      efficacy of on-demand therapy. The goals of treatment of e-GERD should be to
      relieve symptoms and to heal lesions. Symptom severity and much less endoscopic
      abnormalities drives the therapeutic choices. When symptoms are mild or
      intermittent and when oesophagitis is of limited degree, standard dose proton
      pump inhibitor is usually instituted. Fewer and fewer clinicians would still opt
      for an H2-receptor antagonist. If there is moderate or severe oesophagitis or if
      symptoms are particularly troublesome, then the patient should start with
      standard-dose proton pump inhibitor therapy once a day, but not uncommonly a b.d.
      dosage maybe necessary. Once the dose of the acid suppressant that relieves
      symptoms is found, this dose should be maintained for a period of 3 months. After
      this time, an attempt should be made to reduce the dose. If symptoms recur, then
      the patients should go back to the full-dose proton pump inhibitor and a plan
      should be formulated for long-term treatment. The long-term treatment options
      vary between ongoing acid and suppressant therapy, with occasional attempts to
      reduce the dose, or to go for 'on demand' therapy and (rarely) includes
      consideration for surgery or endoscopic anti-reflux therapy.

PMID- 12786614
TI  - Review article: test and treat or treat and test in reflux disease?
AB  - The role of diagnostic testing in reflux disease is in evolution. There is little
      question that patients with dysphagia, bleeding or other 'alarm' symptoms, should
      undergo early endoscopy. A substantial proportion of patients presenting with
      reflux symptoms have endoscopy negative reflux disease. pH testing is both
      inconvenient and lacks the sensitivity and specificity required for a 'gold
      standard'. Empirical trials of therapy using proton pump inhibitors have shown
      that a trial of treatment may be the most accurate way of diagnosing gastro
      oesophageal reflux disease (GERD) and may the optimal strategy from a cost
      effectiveness standpoint. On the other hand, the increasing rate of oesophageal
      adenocarcinoma has raised questions about the possible value of screening
      endoscopy to determine if Barrett's oesophagus is present. The role of endoscopic
      testing in the average patient is therefore shifting from a diagnostic modality
      to one that helps manage risk by identifying Barrett's oesophagus.

PMID- 12786615
TI  - Review article: indications for anti-reflux surgery in gastro-oesophageal reflux
      disease.
AB  - Gastro-oesophageal reflux disease (GERD) is a complex multifactorial disorder
      whose treatment is based on knowledge of its pathophysiology, natural history and
      evolution. Recently the relationship between the severest degrees of cardial
      incontinence and hiatus hernia has been emphasized, which causes the impairment
      of the mechanical properties of the gastro-oesophageal barrier and of oesophageal
      acid clearing. Among different types of hiatus hernia, those characterized by the
      permanent axial orad migration of the oesophago-gastric (EG) junction
      (nonreducible hiatus hernia) are correlated with severe GERD. Barium swallow may
      adequately differentiate hiatal insufficiency, concentric hiatus hernia and short
      oesophagus which are the steps of migration across or above the diaphragm. When
      associated with panmural oesophagitis and fibrosis of the oesophageal wall, these
      conditions may be the cause of recurrence of hiatus hernia and reflux after
      laparoscopic standard anti-reflux surgical procedures; in the presence of
      nonreducibility of the EG junction below the diaphragm without tension, dedicated
      surgical procedures are necessary. It is currently agreed that surgical therapy
      is indicated for patients affected by severe GERD who are not compliant with long
      term medical therapy, require high dosages of drugs and are too young for
      lifetime medical treatment. While the existence of severe GERD correlated with an
      irreversible anatomical disorder represents an elective indication for surgery,
      warrants further investigation. Accurate identification of the functional and
      anatomical abnormalities underlying GERD is mandatory in order to decide whether
      medical or surgical therapy should be implemented, and to tailor the surgical
      technique, laparoscopic or open, to each patient.

PMID- 12786616
TI  - Review article: what have we learnt from gastric biopsy?
AB  - Pathologists would claim that the most reliable information obtained on gastric
      diseases is pathology-based. This manuscript summarizes the four major biopsy
      based contributions to the current knowledge of non-neoplastic gastric diseases:
      (i) the in vivo definition of gastritis; (ii) the recognition of the
      clinicopathological patterns of gastritis; (iii) the morphological links between
      gastritis and stomach cancer; and finally (iv) the recent information on the
      possible reversibility of early or advanced precancerous gastric lesions.

PMID- 12786617
TI  - Review article: molecular basis of gastric carcinogenesis.
AB  - Gastric cancer is constituted by two histomorphological entities 'intestinal' and
      'diffuse', however lesions with similar morphologies may differ in biological
      aggressiveness and response to therapy. Two distinct molecular pathways have been
      identified in gastric carcinogenesis: the microsatellite mutator phenotype and a
      phenotype associated with chromosomal and intrachromosomal instability. Mounting
      evidence suggests that microsatellite mutator phenotype alterations and
      expression of the products of cancer-related genes are early markers of cell
      transformation, and may serve to identify the gastric carcinoma histotypes. The
      lack of a clear genetic basis, lends weight to the notion that gastric cancer is
      not a monomorphic entity but may be affected by environmental factors.
      Helicobacter pylori is the most important environmental risk factor associated
      with sporadic gastric cancer. Exposure of gastric epithelial cells to bacterium
      results in the generation of reactive oxygen species and inducible nitric oxide
      synthase that in turn may cause genetic alterations leading to cancer in a subset
      of subjects. Thus, gastric cancer may be considered the result of an interplay
      between host genetic profile and environmental toxic agents. The new technologies
      of molecular analysis will help to establish an individual's risk of developing
      gastric cancer and will lead to novel biological therapeutic strategies.

PMID- 12786618
TI  - Review article: test and treat or test and scope for Helicobacter pylori
      infection. Any change in gastric cancer prevention?
AB  - A 'test and treat' strategy is advocated for patients with dyspepsia under the
      age of 45 years, with endoscopy reserved for those with alarm symptoms or aged
      over 45 years. One of the consequences of this strategy will be a reduction in
      population infection rates of Helicobacter pylori. It is now clear that H. pylori
      is one of the prime initiators of gastric cancer with up to 70% of gastric
      cancers attributable to H. pylori. What remains unclear is if H. pylori reduction
      will lead to a reduction in gastric cancer.

PMID- 12786619
TI  - Review article: diagnosis and treatment of Helicobacter: a 2002 updated review.
AB  - The year 2002 saw advances on many fronts in the study of Helicobacter and
      gastroduodenal disease. Several studies have confirmed endoscopy as a valuable
      management procedure with confirmation of the diagnostic utility of the rapid
      urease test and the description of a new formulation of the test, which is more
      rapid in giving a result. Serology has been re-confirmed as a useful
      investigation in selected populations. Some commercial kits for near patient
      testing have also been assessed and although generally regarded as less accurate
      than laboratory based tests some have shown acceptable accuracy. The recent
      exciting development in diagnostic serology is the availability of the faecal
      antigen test; further studies have confirmed its usefulness as recommended
      screening tests. There have been several studies demonstrating that a test and
      treat policy has a significant patient benefit, both economic and medical,
      although there is some doubt if eradication of Helicobacter leads to regression
      of atrophy and metaplasia. However, in low Helicobacter-prevalence areas the test
      and treat policy is being challenged as an effective management strategy. Further
      studies have shown that compliance with treatment regimens is an important
      determinant of successful eradication. Finally several new eradication regimens
      have been reported particularly for use in patients who have had previous
      unsuccessful eradication attempts.

PMID- 12786620
TI  - Review article: natural history and prognostic prediction of patients with
      hepatocellular carcinoma.
AB  - The knowledge of the natural history of patients with hepatocellular carcinoma is
      important to estimate the prognosis at diagnosis and indicate the best therapy.
      Prognosis is related to tumour stage at diagnosis, degree of liver function
      impairment induced either by the tumour itself or by the underlying cirrhosis,
      general physical condition of the patients, and potential impact of therapy.
      Prognostic estimation should take into account all four aspects. Treatment is
      very relevant to be considered in patients with early stage tumours since
      surgical resection, transplantation or percutaneous ablation provide a high rate
      of complete responses and thus, improve survival. This might be as high as 50-75%
      at 5 years. Patients diagnosed at an intermediate/advanced stage will receive
      palliative treatment and prospective studies have recently redefined the outcome
      predictors of this stratum. Asymptomatic patients in whom the tumour has not
      invaded vessels or disseminated may reach a 50% survival at 3 years, while those
      with adverse predictors do not reach this time point. These data have to be taken
      into account not only in the conventional clinical practice, but also in the
      design and evaluation of prospective investigations that should be properly
      powered to reach an informative sample size. To achieve both aims, within the
      Barcelona Clinic Liver Cancer Group we have developed a staging system that
      combines prognosis prediction with decision making, thus becoming a useful tool
      both for practice and research.

PMID- 12786621
TI  - Review article: percutaneous treatment of hepatocellular carcinoma.
AB  - In early stage hepatocellular carcinoma (HCC), liver transplantation, surgical
      resection and percutaneous techniques are classified as radical treatments, and
      may be offered to about 25% of all patients with HCC evaluated in referral
      centres. The restricted inclusion criteria for surgical resection and the
      shortage of liver donors for transplantation have stimulated an increasing demand
      for minimally invasive treatments able to achieve effective and reproducible
      percutaneous tumour ablation, with less associated morbidity and lower cost than
      other interventions. Among percutaneous techniques, ethanol injection has proven
      to be highly effective in single HCC up to 3 cm, with a rate of complete response
      of 80%, being well tolerated and with a limited risk of minor complication. In
      larger and/or multinodular HCC the efficacy is reduced to 50% of complete
      response in nodules between 3 and 5 cm, and to lower rate in larger tumours.
      Alternative options to ethanol injection have been recently proposed, including
      radiofrequency, microwave and laser thermal ablation, aimed to extend the
      necrotic area thus improving the rate of complete response. To date,
      radiofrequency is the most used technique, with a reported rate of complete
      response of 90-98% in nodules smaller than 3 cm, and with the advantage of fewer
      sessions, otherwise counteracted by a higher rate of side-effects. Microwave and
      laser are promising technologies, but only few clinical data are available.
      Randomized controlled trials are needed in order to assess treatment response,
      long-term survival, rate of complication and cost-efficacy of newer technologies
      in comparison to ethanol injection.

PMID- 12786622
TI  - Review article: intra-arterial treatments in patients with hepatocellular
      carcinoma.
AB  - In Western countries, most of the patients with hepatocellular carcinoma (HCC)
      are not eligible for curative treatments. Intra-arterial treatments have a
      palliative effect that could lead to extensive tumour necrosis and therefore have
      been widely used. Arterial embolization, Lipiodol-targeted chemoembolization and
      intra-arterial injection of radioactive iodine mixed with Lipiodol provided
      promising results in terms of tumoral growth, but were also responsible for
      severe side-effects, particularly in patients with cirrhosis. Their influence on
      survival has been assessed by randomized trials with contradictory results. In
      patients with advanced cases, embolization alone has limited or no influence on
      survival, and chemoembolization provided a beneficial effect mostly in patients
      with viral liver diseases, without liver failure, and with an adequate portal
      flux. The effects of radioactive iodine either in the treatment of advanced cases
      or the prevention of recurrences after a curative treatment must be investigated
      further.

PMID- 12786624
TI  - Review article: hepatocellular carcinoma: indications for liver transplantation.
AB  - The role of liver transplantation for hepatocellular carcinoma has evolved over
      the years and currently is one of the curative therapies for small tumours. The
      survival rates are similar with those for nonmalignant liver disease after
      transplantation. The treatment of small tumours eligible for both resection and
      transplantation depends on the experience of the transplant centre and the
      waiting time for a liver graft. With waiting times for liver transplant becoming
      gradually longer, prioritization of the tumour patients has been suggested.
      Adjuvant therapies may delay the tumour progression while patients wait for a
      transplant. The living donor and the domino liver transplantation are useful
      alternatives given the shortage of organs but the experience is still limited in
      the Western world and the selection for the domino livers is fairly restricted.

PMID- 12786623
TI  - Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics.
      Evaluation of clinicopathologic features and comparison of risk factors for long
      term survival and tumour recurrence in a single centre.
AB  - BACKGROUND: Differences in risk factors for survival and recurrence after liver
      resection for hepatocellular carcinoma (HCC) in patients with or without
      cirrhosis are not fully clarified. AIM: To review a single-centre experience of
      curative liver resections for HCC in order to evaluate clinicopathologic features
      and the long-term outcome of cirrhotic and noncirrhotic patients. METHODS: From
      1981 to 2002, 308 curative liver resections for HCC on cirrhosis (Group 1) and
      135 for HCC without cirrhosis (Group 2) were performed. The main demographic,
      clinicopathologic and operative parameters, as well as early results were
      analysed and compared. Overall and disease-free survival were evaluated.
      Prognostic factors for survival and for tumour recurrence were studied by
      univariate and multivariate analysis. RESULTS: Group 1 had worse preoperative
      liver function and higher frequency of hepatitis C virus infection. In Group 2,
      HCC showed larger mean tumour diameter (P < 0.001), poorer differentiation (P <
      0.05) and more frequent macrovascular invasion (P < 0.05). Although more extended
      resections were performed in Group 2 (P < 0.001), there were no differences in
      blood transfusions, while post-operative complication rate was higher in Group 1
      (P < 0.005). After 1992, in-hospital mortality was 2.9% in Group 1 and 1.1% in
      Group 2 (P = N.S.). The 3- and 5-year overall survival was 63.7% and 42.2% in
      Group 1, and 67.9% and 51% in Group 2 (P < 0.05). The 3- and 5-year disease-free
      survival was 49.3% and 27.8% in Group 1, and 58% and 45.6% in Group 2 (P <
      0.005). Serum bilirubin level > 1.2 mg/dL, multiple nodules, micro and
      macrovascular invasion, diaphragm infiltration and blood transfusions
      independently affected survival in Group 1. Blood replacement was the only
      negative prognostic factor in Group 2. Independent risk factors for tumour
      recurrence were satellite nodules and resection performed before 1992 in Group 1,
      and age < 60 in Group 2. CONCLUSIONS: Despite a more aggressive behaviour, HCC
      without cirrhosis led to better overall and disease-free survival compared to HCC
      with cirrhosis after curative liver resection. Age and intra-operative blood
      transfusions are the only predictors of outcome in patients without cirrhosis.
      The impact of the latter on long-term survival in both our groups outlines the
      importance of surgical technique on the results of hepatectomies.

PMID- 12786625
TI  - Review article: liver transplantation for hepatocellular carcinoma.
AB  - Despite recent advances in techniques of in situ tumour ablation, surgical
      therapy remains at present the mainstay treatment for primary hepatic
      malignancies. After an initial endeavour in the establishment of liver
      transplantation as a treatment option, in particular for unresectable liver
      tumours, only a few indications, for example early hepatocellular carcinoma in
      cirrhosis, are currently agreed upon. Other indications, such as peripheral
      cholangiocarcinoma and hepatocellular carcinoma in noncirrhotics have largely
      been abandoned or are still under debate, as is the case with fibrolamellar
      carcinoma. The selection of patients suffering from hepatocellular carcinoma in
      cirrhosis for liver transplantation is still based on tumour size and node
      number, because the current state of diagnostic imaging fails to reliably predict
      the most important prognostic parameter: vascular infiltration. Other selection
      criteria are under investigation. Studies on multimodal therapy are also underway
      but have not yet demonstrated a clear benefit.

PMID- 12786626
TI  - Review article: liver transplantation for HCC. Treatment options on the waiting
      list.
AB  - The most widely adopted criteria to admit and maintain patients with HCC and
      cirrhosis in the waiting list for liver transplantation are the Milano criteria,
      consisting in the presence of a single tumour <or=5 cm in diameter or up to three
      tumours, none exceeding 3 cm in diameter. Since the average time to
      transplantation has become longer than 10-12 months in most European and American
      Centers, the exclusion from the list during the waiting period due to increase of
      the neoplasm over the established criteria is not uncommon at present. It is
      mandatory, therefore, to seek an effective therapeutic strategy for patients with
      HCC waiting for transplantation. Surgical resection and eventual subsequent
      salvage transplantation seems a cost-effective strategy in resectable HCC. In
      unresectable neoplasms both transarterial chemoembolization and percutaneous
      ablation techniques are currently used and one or the other are chosen according
      to individual applicability, limitations and specific risks. However, although
      positive trends were reported, no definitive evidence has been produced so far
      about their efficacy in increasing patient's survival and decreasing tumour
      recurrence rates after transplantation. Adult-to-adult living donor liver
      transplantation is one possible way to shorten the waiting list, but this
      strategy involves important ethical implications. At present it appears justified
      to take it into consideration only if the waiting time for cadaveric OLT is
      expected to exceed 7 months. A more general and definitive attempt to overcome
      problems related to long waiting times for patients with HCC and relatively
      preserved hepatic function has been introduced in the USA very recently and
      consists in prioritizing patients with HCC. However, the overall efficacy of this
      approach will be established only in some years.

PMID- 12786627
TI  - Review article: the treatment of refractory Helicobacter pylori infection.
AB  - The occurrence of refractory Helicobacter pylori infection is increasing. When
      the bacteria are not eradicated it means that the antibiotics have not reached
      the gastric mucosa at a sufficient concentration and over a sufficient time lapse
      to kill them. The main reasons for this are poor patient compliance, resistant
      bacteria, low gastric pH and a high bacterial load. Therefore, when administering
      a new treatment, it is important to choose antibiotics which do not face
      resistance problems and which increase the dosage of antisecretory drugs and the
      duration of treatment and, if possible, to add a topical agent such as bismuth
      salt. The recommended empirical strategy is to prescribe quadruple therapy or,
      alternatively, 2-week triple therapy including amoxicillin-metronidazole,
      tetracycline-metronidazole or amoxicillin-rifabutin. However, when H. pylori is
      susceptible, clarithromycin can still be used. In the case of a high level of
      metronidazole resistance, furazolidone can be employed. In each case, it is
      important to ensure good patient compliance, and counselling is helpful in this
      regard. However, the best approach remains the prevention of refractory H. pylori
      infection and, for this purpose, antimicrobial susceptibility testing before
      first-line therapy is important and should be encouraged.

PMID- 12786628
TI  - Review article: clinic-based testing for Helicobacter pylori infection by enzyme
      immunoassay of faeces, urine and saliva.
AB  - Enzyme immunoassays have been used to detect Helicobacter pylori infection in
      human body materials such as faeces, urine and saliva. The stool antigen assay
      (HpSA), which uses polyclonal anti-H. pylori antibody as a capture reagent, has
      been widely used in the pre-treatment diagnosis of the infection in adults and
      children. Although the assay has the potential for monitoring eradication
      therapy, there are controversies over its use, especially at an early stage after
      treatment. The efficacy of the stool antigen assay can be modified by using
      monoclonal antibodies towards well characterized H. pylori faecal antigens. Two
      types of enzyme immunoassays (enzyme-linked immunosorbent assay [ELISA] and
      immunochromatography) have been used to detect antibodies to H. pylori in urine.
      Immunochromatography of urine is a rapid assay well suited for epidemiological
      studies. The salivary ELISA, used in a number of studies, has shown inconsistent
      results with less than optimum sensitivity and specificity. Urinary and salivary
      immunoassays may not distinguish between past and present infections, thus
      limiting their potential to monitor eradication therapy.

PMID- 12786629
TI  - Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative
      colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
AB  - BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce
      inflammation in animal models of colitis. AIM: To evaluate repifermin for the
      treatment of active ulcerative colitis. METHODS: Eighty-eight patients with
      active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients
      were randomized to receive treatment for five consecutive days with intravenous
      repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary
      objective of the study was to evaluate the safety of repifermin. The primary
      efficacy outcome was clinical remission at week 4, defined as a score of zero on
      the endoscopic appearance and stool blood components of the Mayo score and a
      score of zero or unity on the stool frequency and physician's global assessment
      components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10,
      25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively,
      and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The
      frequencies of commonly occurring adverse events and severe adverse events were
      similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50
      microg/kg was very well tolerated, but there was no evidence that repifermin was
      effective for the treatment of active ulcerative colitis at these doses. An
      additional study to determine the efficacy of repifermin at doses of > 50
      microg/kg or for a longer treatment duration may be warranted, as the maximally
      tolerated dose was not reached in the present study.

PMID- 12786630
TI  - Mycophenolate mofetil in refractory inflammatory bowel disease.
AB  - BACKGROUND: Mycophenolate mofetil has been claimed to be effective and well
      tolerated in refractory inflammatory bowel disease although there is little
      information regarding its use in clinical practice. AIM: To review our experience
      in achieving and maintaining remission in refractory inflammatory bowel disease
      and to document tolerability, major toxicity and efficacy. METHODS: A
      retrospective audit was performed of the records of all patients with
      inflammatory bowel disease treated with mycophenolate mofetil (1-2 g/day) over a
      3-year period. RESULTS: Thirty-nine patients were identified. Almost all had been
      intolerant of, or had not responded to azathioprine, and 38 were steroid
      dependent. mycophenolate mofetil was discontinued in 22 patients, 11 due to
      intolerance and 10 because of lack of efficacy. Of the 17 on treatment at the end
      of the study period 16 were in remission and off all steroid therapy, but one
      needed infliximab to maintain remission. No major toxicity was noted and there
      was no major sepsis. CONCLUSIONS: Approximately 40% of patients with severe
      refractory inflammatory bowel disease achieved remission and complete steroid
      withdrawal on mycophenolate mofetil therapy, almost 30% could not tolerate the
      drug, and a further 30% did not respond. Mycophenolate mofetil therapy may have a
      role for steroid-dependent patients refractory to azathioprine.

PMID- 12786631
TI  - An open-label trial of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, in
      inflammatory bowel disease-associated peripheral arthritis and arthralgia.
AB  - BACKGROUND: Conventional non-steroidal anti-inflammatory drugs have been
      associated with an increased risk of exacerbation of inflammatory bowel disease.
      AIM: To evaluate, in a prospective, open-label study, the safety and efficacy of
      a 20-day regimen of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, 12.5-25
      mg/day, in inflammatory bowel disease patients with associated peripheral
      arthropathy and/or arthritis. METHODS: Patients with clinically inactive to mild
      inflammatory bowel disease and a joint pain score of at least two points on a
      scale ranging from zero (none) to four (very poor) were eligible. Response was
      defined by a decrease of at least two points in the arthralgia score. RESULTS: Of
      the 32 patients included, 26 (81%) were treated with rofecoxib, 25 mg/day, and
      six (19%) with rofecoxib, 12.5 mg/day. In three patients (9%), rofecoxib had to
      be withdrawn after a few days due to gastrointestinal complaints which ceased
      immediately after drug discontinuation. No flare of inflammatory bowel disease
      occurred. Thirteen of the 32 patients (41%) were responders and, overall, the
      arthralgia score decreased from two to one (P = 0.0001). CONCLUSIONS: This is the
      first prospective study on the use of a selective cyclo-oxygenase-2 inhibitor in
      inflammatory bowel disease patients with peripheral arthropathy and/or
      arthralgia. The promising safety and efficacy profile warrants further evaluation
      in controlled trials.

PMID- 12786632
TI  - One-week triple therapy with esomeprazole, clarithromycin and metronidazole
      provides effective eradication of Helicobacter pylori infection.
AB  - AIM: To compare the eradication rates of treatment with esomeprazole,
      metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and
      clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of
      treatment with 20 mg omeprazole alone; the EMC group received placebo. METHODS: A
      randomized, double-blind, controlled study was conducted in 36 Canadian centres.
      Patients had a minimum 3-month history of dyspepsia, with or without a previous
      history of peptic ulcer disease, and were Helicobacter pylori positive by urea
      breath test. The eradication of H. pylori was determined by two negative breath
      tests performed at least 4 and 8 weeks following the completion of treatment.
      RESULTS: The intention-to-treat and per protocol populations consisted of 379 and
      339 patients, respectively. The success rates of EMC/placebo were 76% (144/190)
      by intention-to-treat and 80% (138/172) by per protocol analysis; for
      OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The
      difference between the two treatment groups was not significant. Treatment was
      well tolerated. CONCLUSIONS: A 7-day regimen of esomeprazole, metronidazole and
      clarithromycin is effective and well tolerated for the eradication of H. pylori
      infection.

PMID- 12786633
TI  - Is irritable bowel syndrome more likely to be persistent in those with relatives
      who suffer from gastrointestinal symptoms? A population-based study at three time
      points.
AB  - BACKGROUND: We tested the hypothesis that subjects with relatives who suffered
      from abdominal pain or bowel dysfunction would be at an increased risk of more
      persistent irritable bowel syndrome. METHODS: A valid, self-report questionnaire
      was mailed to an age- and gender-stratified random sample of residents, aged 30
      64 years, in Olmsted County, MN, USA, on three occasions over a 4-year period.
      Persistent irritable bowel syndrome was defined as the presence of irritable
      bowel syndrome on at least two of the three surveys, and fluctuating irritable
      bowel syndrome was defined as the presence of irritable bowel syndrome on only
      one of the surveys. RESULTS: Subjects were less likely to have persistent
      irritable bowel syndrome over the age of 50 years [odds ratio (OR), 0.20; 95%
      confidence interval (CI), 0.09, 0.47]. A positive family history was reported by
      23%. A family history of gastrointestinal symptoms was independently associated
      with persistent irritable bowel syndrome (vs. no irritable bowel syndrome: OR,
      2.5; 95% CI, 1.3, 4.9) and fluctuating irritable bowel syndrome (vs. no irritable
      bowel syndrome: OR, 2.4; 95% CI, 1.3, 4.4). However, subjects reporting a
      positive family history were not more likely to report persistent vs. fluctuating
      irritable bowel syndrome (OR, 1.2; 95% CI, 0.5, 2.9). The use of non-steroidal
      anti-inflammatory drugs (OR, 2.3; 95% CI, 1.2, 4.3) and a history of food
      sensitivity (OR, 3.6; 95% CI, 1.9, 6.9) were the only other predictors of
      persistent irritable bowel syndrome. CONCLUSIONS: A history of abdominal pain or
      bowel troubles in first-degree relatives appears to be independently associated
      with both persistent and fluctuating irritable bowel syndrome.

PMID- 12786634
TI  - Short- and long-term therapy for reflux oesophagitis in the elderly: a multi
      centre, placebo-controlled study with pantoprazole.
AB  - BACKGROUND: No placebo-controlled clinical trials have yet been published on the
      efficacy of therapy in older subjects with oesophagitis. AIM: To evaluate the
      efficacy of pantoprazole in preventing the recurrence of oesophagitis in elderly
      subjects. METHODS: One hundred and sixty-four patients aged 65 years and over
      with acute oesophagitis were treated openly with pantoprazole, 40 mg daily, for 8
      weeks. Patients with documented healing of erosive oesophagitis were then treated
      with pantoprazole, 20 mg daily, for 6 months. Thereafter, cured patients were
      randomized to receive pantoprazole, 20 mg daily, or placebo for the following 6
      months. Clinical evaluations were performed every 2 months, and endoscopy was
      repeated after 8 weeks and after 6 and 12 months and/or whenever symptoms
      suggested a relapse of oesophagitis. RESULTS: After 8 weeks, the healing rates of
      oesophagitis were 81.1% (75.1-87.1%) and 93.7% (89.7-97.7%) by intention-to-treat
      and per protocol analyses, respectively. After 6 months, the corresponding values
      were 82% (75.4-88.5%) and 92.4% (87.6-97.2%), respectively. After 12 months, the
      per protocol and intention-to-treat healing rates of oesophagitis were 95.1%
      (88.5-100%) and 79.6% (68.3-90.9%), respectively, in the treatment group vs.
      32.7% (19.9-45.4%) and 30.4% (18.3-42.4%), respectively, in the placebo group (P
      = 0.0001). Heartburn, acid regurgitation and chest pain were significantly
      associated with the relapse of oesophagitis (P = 0.0001), whereas hiatus hernia,
      Helicobacter pylori infection, concomitant diseases and treatments were not.
      CONCLUSION: In the elderly, pantoprazole was highly effective in healing and
      reducing the relapse of oesophagitis; discontinuing active treatment after 6
      months was associated with a significant increase in the relapse rate.

PMID- 12786635
TI  - A validated symptoms questionnaire (Chinese GERDQ) for the diagnosis of gastro
      oesophageal reflux disease in the Chinese population.
AB  - BACKGROUND AND AIMS: To develop a validated gastro-oesophageal disease (GERD)
      symptom questionnaire for the Chinese population. METHODS: One hundred Chinese
      patients with GERD and 101 healthy Chinese controls were presented with a 20-item
      GERD questionnaire in the Chinese language (Chinese GERDQ). Quality of life in
      GERD patients was assessed by SF-36. A standard dose of proton pump inhibitors
      for 4 weeks was prescribed to 35 patients with newly diagnosed GERD. The Chinese
      GERDQ was performed before, 4 weeks and 8 weeks after treatment. Concept,
      content, construct, discriminant validity and reliability of the questionnaire
      were assessed. RESULTS: Seven items were selected by logistic regression to
      account for most of the differences between controls and GERD patients with a
      good reproducibility and internal consistency. A cut-off score of equal or
      greater than 12 was determined to discriminate between controls and GERD patients
      with a sensitivity of 82% and a specificity of 84%. The Chinese GERDQ correlated
      negatively with five domains of the SF-36 and discriminated between GERD patients
      who reported symptomatic improvement during proton pump inhibitor treatment and
      symptoms deterioration upon withdrawal of proton pump inhibitor treatment.
      CONCLUSIONS: The Chinese GERDQ could be used in epidemiological studies to assess
      the frequency and severity of GERD in patient populations and in interventional
      studies of GERD.

PMID- 12786636
TI  - Antibodies to human recombinant tissue transglutaminase may detect coeliac
      disease patients undiagnosed by endomysial antibodies.
AB  - BACKGROUND: The screening and diagnosis of coeliac disease have been simplified
      by the advent of new serological tools. AIM: To assess the clinical utility of a
      newly developed kit for antibodies to human recombinant tissue transglutaminase
      (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for
      suspected intestinal disorders. METHODS: We evaluated 426 serum samples from
      consecutive adult patients (250 from untreated coeliac disease patients and 176
      from individuals in whom a diagnosis of coeliac disease had been excluded),
      obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin
      A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial
      antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin
      antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was
      also assessed for a guinea-pig-based anti-tissue transglutaminase. RESULTS:
      According to the cut-off for hu-anti-tTG, the sensitivity, specificity and
      positive and negative predictive values were 91%, 96%, 97% and 87%, respectively.
      Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for
      the same parameters. Although 19 coeliac disease patients (7.6%) were negative
      for EmA and hu-anti-tTG, both tests rendered superior statistical values to
      antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11
      patients, but both assays were able to detect samples with mild to moderate
      deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance
      between the tests (kappa statistic, 0.85). Discordance was observed in 20 samples
      from coeliac disease patients (8%) and in nine samples from controls (5%).
      Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five
      showed the converse pattern. Comparison of human recombinant and guinea-pig tests
      showed concordant results in 96% of cases. CONCLUSIONS: The quantitative
      determination of hu-anti-tTG type IgA using a commercial enzyme-linked
      immunoabsorbent assay kit was highly sensitive and specific for the detection of
      coeliac disease. Our results in a large population of patients with a clinical
      condition suggestive of the disorder demonstrated that the test can be used to
      detect a substantial number of patients otherwise unrecognized by IgA EmA.

PMID- 12786637
TI  - Serotonergic modulators in the treatment of irritable bowel syndrome: influence
      on psychiatric and gastrointestinal symptoms.

PMID- 12786638
TI  - Emergency women's health.

PMID- 12786639
TI  - The problem facing the expert medical witness: does the tail wag the dog?

PMID- 12786640
TI  - Abnormal vaginal bleeding.
AB  - The complaint of abnormal vaginal bleeding in a non-pregnant patient is not a
      common presentation to a general ED. However, the bleeding may in itself be
      significant or it may be a harbinger of serious underlying pathology. A
      systematic approach to diagnosis is required. An initial approach to vaginal
      bleeding can be to categorize the bleeding by the anatomical site. This article
      discusses some of the common causes of upper tract or uterine bleeding and
      outlines the basic approach to diagnosis and management.

PMID- 12786641
TI  - Current challenges in the assessment and management of patients with bleeding in
      early pregnancy.
AB  - Bleeding in early pregnancy occurs in approximately 20% of clinically diagnosed
      pregnancies. History and physical examination are unable to reliably determine
      the anatomical location of the pregnancy (ectopic or intrauterine) or whether or
      not the fetus is alive. Ultrasound is the best tool for assessing these clinical
      questions and it is increasingly being used in the ED. This article looks at some
      of the common ultrasound findings and discusses the management options for failed
      and ectopic pregnancies.

PMID- 12786642
TI  - Female sexual health.
AB  - Many aspects of sexual health relate to either preventative medicine
      (contraception) or managing normal physiological states (pregnancy, menopause).
      This article looks at some of the emergency aspects of female sexual health
      including genital tract trauma and genital infections.

PMID- 12786643
TI  - Obstetric haemorrhage.
AB  - Few obstetric emergencies cause greater concern than haemorrhage in late
      pregnancy and the immediate postpartum period. Massive haemorrhage can occur
      without forewarning with few reliable clinical indicators available to predict
      those at greatest risk. Patients may remain haemodynamically stable until a
      sudden deterioration in condition takes place. In many cases the extent of the
      bleeding can be unclear as the haemorrhage may be concealed behind the placenta.
      This article reviews the common causes of ante and postpartum haemorrhage, their
      associated factors and the immediate and subsequent management of the conditions.
      A variety of uterotonic agents is available for the treatment of postpartum
      haemorrhage and a structured approach for their use is required.

PMID- 12786644
TI  - Reduced access block causes shorter emergency department waiting times: An
      historical control observational study.
AB  - OBJECTIVE: To study the effect of changes in hospital occupancy and ED occupancy
      on ED waiting times during a 13-day period of improved bed access. METHODS: A
      comparative, observational study of 1133 ED attendances in the study period and
      2332 attendances in a historical control period. RESULTS: During the study
      period, mean hospital occupancy decreased from 94.9% to 89.0% (P < 0.001), mean
      ED occupancy decreased from 19.1 to 14.8 patients (P < 0.001) and the mean ED
      waiting time decreased from 58.5 to 37.1 min (P < 0.001). There were
      statistically significant reductions in waiting times for patients in
      Australasian triage scale (ATS) categories 2-5. Departmental staffing levels,
      attendances and patient acuity were not significantly different during the study
      and control periods. CONCLUSIONS: Modest decreases in hospital occupancy resulted
      in highly significant reductions in ED waiting times. Emergency department
      overcrowding due to large numbers of admitted patients awaiting hospital
      admission is a major cause of ED dysfunction.

PMID- 12786645
TI  - Implications for urgent transfusion of uncrossmatched blood in the emergency
      department: The prevalence of clinically significant red cell antibodies within
      different patient groups.
AB  - OBJECTIVE: To define the prevalence of alloantibodies as a factor of age and
      underlying clinical disease, with particular relevance to the prediction of the
      safety of uncrossmatched blood in different demographic groups. METHODS: A
      retrospective review was conducted of all immunohaematological studies on blood
      samples submitted to the blood bank of a tertiary referral hospital between
      January 1998 and December 1999. RESULTS: A total of 27 968 antibody screens in 15
      966 patients were analysed. When only clinically significant antibodies were
      considered, the total alloimmunization prevalence was 1.9% and the prevalence of
      antibodies capable of causing an immediate transfusion reaction was 0.6%. The
      prevalence of antibodies capable of causing an immediate transfusion reaction was
      0.1% in the under 30 years of age group. Clinically significant antibodies were
      found in 5.1% in the haematology and oncology unit patients. The risk rises with
      age and female sex. CONCLUSION: We conclude that uncrossmatched blood is
      associated with low risk in patients < 30 years of age. The knowledge that
      patients have not been exposed to previous transfusion or pregnancy will reduce
      the risk even further.

PMID- 12786646
TI  - Accidental poisoning in New Zealand.
AB  - OBJECTIVE: To examine mortality and morbidity associated with accidental
      poisoning in New Zealand for the period of 1993-97, and make comparisons with
      international trends. METHODS: Poison Centre call data, and mortality and public
      hospital discharge data from the New Zealand Health Information Service were
      examined. Mortality and hospitalization rates were calculated. Statistical trends
      were examined using Poisson regression. RESULTS: Poison Centre calls regarding
      household agents and therapeutics were most frequent. Accidental poisoning with
      analgesics, antipyretics and antirheumatics (18%) was a common cause of
      hospitalization. Children under 5 years had the highest hospitalization rates,
      but were less at risk of death by accidental poisoning than other age groups.
      Common causes of death from accidental poisoning included utility gas/carbon
      monoxide (16%), psychotropic agents (16%), and analgesics, etc. (15%). Mortality
      rates varied between 0.54 and 0.72/100,000 population. CONCLUSION: Mortality
      rates in New Zealand are lower than in many countries, but hospitalization rates
      are higher. Possible explanations and prevention implications are discussed.

PMID- 12786647
TI  - Diagnosing pulmonary embolism: a question of too much choice?
AB  - The diagnosis of pulmonary embolism (PE) is difficult with many patients treated
      without the disease or left untreated without an adequate diagnostic work up.
      Recent advances in PE diagnosis are reviewed. The use of risk stratification in
      PE diagnosis is strongly recommended and evidence on how it can best be performed
      summarized. The Ginsberg/Wells stratification rule is recommended currently as
      the best validated rule. Computed tomographic pulmonary angiography (CTPA) was
      found to have quite poor sensitivity and to be poorly validated. It is
      recommended as adequate as a positive test in moderate/high risk groups and an
      exclusionary test in low risk groups or where an adequate alternative diagnosis
      is found. For D-Dimer tests the only test with adequate sensitivity and
      validation in management studies is the VIDASCopyright D-Dimer. This is in
      low/intermediate risk groups in the ED population. The Simpli-RedCopyright test
      is also reviewed but is too insensitive for most populations. Echocardiography:
      this is good in compromised patients as it is a bedside test which when negative
      virtually excludes PE. If positive in the right setting it has a high positive
      predictive value. A negative echocardiogram predicts a benign clinical course for
      PE. The rest of the paper details the authors approach to integrating these new
      techniques with established algorithms and where progress is likely to occur in
      the next few years. These include improvements in CTPA (plus the addition of CT
      venography), new point of care D-Dimer tests, better risk stratification rules
      and integration of new strategies with artificial neural networks or computerized
      guidelines.

PMID- 12786648
TI  - Unethical practices in authorship of scientific papers.
AB  - Over the past few decades, there has been an increase in the number of multi
      author papers within scientific journals. This increase, in combination with the
      pressure to publish within academia, has precipitated various unethical
      authorship practices within biomedical research. These include dilution of
      authorship responsibility, 'guest', 'pressured' and 'ghost' authorship, and
      obfuscation of authorship credit within by-lines. Other authorship irregularities
      include divided and duplicate publication. This article discusses these problems
      and why the International Committee of Medical Journal Editors guidelines are
      failing to control them.

PMID- 12786649
TI  - A strategic plan for disaster medicine in Australasia.
AB  - Disaster epidemiology reveals epidemic increases in incidence of disasters. Rare
      disasters with catastrophic consequences also threaten modern populations. This
      paper profiles natural disasters, transportation incidents, emerging infectious
      diseases, complex disasters and terrorism for their historical and future
      potential impact on Australasia. Emergency physicians are in a position to assume
      leadership roles within the disaster management community in Australasia. The
      Australasian College for Emergency Medicine is in a position to lead medical
      specialty advances in disaster medicine in Australasia. To optimize its impact in
      disaster medicine, the specialty and its College have opportunities for advances
      in key areas of College administration, intra and interinstitutional
      representation, disaster preparedness and planning, disaster relief operations,
      education and training programs, applied clinical research, and faculty
      development.

PMID- 12786650
TI  - The adversarial court system and the expert medical witness: 'The truth the whole
      truth and nothing but the truth?'.
AB  - This discussion aims to provide the occasional medical expert witness with
      background knowledge of the adversarial court system and the role of the medical
      expert witness within it. The parallel evolution of the adversarial and
      inquisitorial legal systems has been more out of tradition rather than any
      systematic review of the effectiveness of one system or the other. Both legal
      systems have their merits and limitations. Witnesses within the adversarial
      system are required to present evidence in a structured and highly stylized
      format consisting of 'evidence in chief' followed by 'cross-examination'. This
      format is an attempt to exclude unreliable evidence. The medical witness is an
      'expert' by means of specialized knowledge not possessed by the general public.
      This distinction allows the expert medical witness to offer his or her opinion as
      evidence. There remain several limitations to the expert's evidence and these
      relate to common knowledge, field of expertise and the 'ultimate issue'. The
      current practice of selection of expert medical witnesses is seriously flawed
      with several pressures operating to maximise bias and inaccurate testimony.
      Doctors should not only anticipate change in this area they should lead reform in
      this area.

PMID- 12786651
TI  - Working as an emergency physician in the United Kingdom.

PMID- 12786652
TI  - Something fishy: six patients with an unusual cause of food poisoning!
AB  - Scombroid fish poisoning is a clinical syndrome attributed to the ingestion of
      contaminated fish. A toxin or toxins, known as scombrotoxin, result from
      decomposition by endogenous flora of the amino acid histidine liberating
      bioactive amines, predominantly histamine. The presentation has features of
      histamine toxicity, typically with urticaria, flushing, headache, abdominal
      cramps, diarrhoea and vomiting. The course is usually mild and self-limiting. The
      author describes six cases of scombroid poisoning after ingestion of fish from
      the same Canberra restaurant. One case resulted in significant hypotension
      necessitating a prolonged stay in the ED.

PMID- 12786653
TI  - An unusual presentation of idiopathic bilateral avascular necrosis of the femoral
      heads.
AB  - A case report is presented of a patient with an unusual presentation of
      idiopathic bilateral avascular necrosis of the femoral heads after a period of
      multiple presentations and misdiagnoses in the ED. This is the first such case
      described presenting in this way and highlights the importance of establishing a
      firm diagnosis and instituting appropriate management.

PMID- 12786659
TI  - Is potassium concentration from arterial blood gas analysis an accurate
      reflection of serum potassium?

PMID- 12786660
TI  - Keeping an eye on optic nerve trauma.

PMID- 12786662
TI  - Safe management of paracetamol overdose for all?

PMID- 12786663
TI  - Calculation of general practice proportion of emergency department casemix.

PMID- 12786667
TI  - Continuing education.

PMID- 12786668
TI  - Teaching and learning in a large group.

PMID- 12786669
TI  - Training in flexible, intensive insulin management to enable dietary freedom in
      people with Type 1 diabetes: dose adjustment for normal eating (DAFNE) randomized
      controlled trial.

PMID- 12786670
TI  - Structured patient group education and Type 1 diabetes.

PMID- 12786672
TI  - One-to-one care and education, old hat now?

PMID- 12786673
TI  - Management of hyperglycaemia in the patient with acute myocardial infarction.

PMID- 12786675
TI  - Cystic fibrosis-related diabetes.
AB  - Diabetes mellitus (DM) has been recognized as a complication of cystic fibrosis
      (CF) for almost 50 years and commonly develops around 20 years of age. The
      prevalence increases with age and, with improved survival of those with CF,
      approaches 30% in certain centres. Its development appears to have a significant
      impact on pulmonary function and may increase mortality by up to six-fold.
      Subjects with CF are rarely ketosis-prone and phenotypically lie between Type 1
      and Type 2 DM. Microvascular complications are recognized, although paucity of
      data does not permit a clear description of their natural history. An annual oral
      glucose tolerance test from the age of 10 years is recommended for screening, but
      logistical difficulties have led some groups to develop specific algorithms to
      aid diagnosis. Insulin sensitivity in CF is much debated and may depend upon the
      degree of glucose intolerance. Insulin resistance occurs in the presence of
      infection, corticosteroid usage and hyperglycaemia, whilst hepatic insulin
      resistance is considered an adaptation to CF. There is no universal consensus on
      the treatment of hyperglycaemia. With increased longevity of individuals with CF,
      greater numbers will develop diabetes and the diabetes physician is destined to
      play a greater role in the multidisciplinary CF team.

PMID- 12786676
TI  - Type 1 diabetes in Yorkshire, UK: time trends in 0-14 and 15-29-year-olds, age at
      onset and age-period-cohort modelling.
AB  - AIMS: To investigate whether the rising incidence of Type 1 diabetes in children
      is evident in young adults and determine whether age at onset has decreased over
      time. METHODS: Two geographically defined datasets from the population-based
      Yorkshire Diabetes Register were analysed: (i) 2718 children diagnosed under 15
      years with Type 1 diabetes from 1978 to 2000 in Yorkshire; (ii) 631 young adults
      (15-29 years) diagnosed from 1991 to 1999 in West Yorkshire. Log-linear
      regression and age-period-cohort modelling evaluated changes in incidence over
      time and age at onset. RESULTS: Incidence rose steadily for 0-14-year-olds in
      Yorkshire with an average annual increase of 2.9%[95% confidence interval (CI)
      2.0, 3.8]. In West Yorkshire between 1991 and 1999, the time trends for 0-14 and
      15-29-year-olds were significantly different (P = 0.014). Stable rates in 15-29
      year-olds contrasted with an average annual increase of 5.9% (95% CI 2.7, 9.2)
      for 0-14-year-olds. The mean age at onset fell from 9.2 to 8.4 years for 0-14
      year-olds and from 16.0 to 14.6 years for 0-29-year-olds. Age-period-cohort
      modelling showed a statistically significant (P < 0.001) increased risk of
      developing diabetes was associated with decreasing age for those diagnosed more
      recently. CONCLUSIONS: A steady and continuing rise in the incidence of Type 1
      diabetes over time is observed for children but not for young adults. In
      parallel, the age at onset is gradually decreasing and more recent birth cohorts
      are at increased risk. This overall pattern is consistent with the influence of
      an environmental agent that is gradually affecting children at younger and
      younger ages.

PMID- 12786677
TI  - The impact of diabetes-related complications on healthcare costs: results from
      the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65).
AB  - AIMS: To develop a model for estimating the immediate and long-term healthcare
      costs associated with seven diabetes-related complications in patients with Type
      2 diabetes participating in the UK Prospective Diabetes Study (UKPDS). METHODS:
      The costs associated with some major complications were estimated using data on
      5102 UKPDS patients (mean age 52.4 years at diagnosis). In-patient and out
      patient costs were estimated using multiple regression analysis based on costs
      calculated from the length of admission multiplied by the average specialty cost
      and a survey of 3488 UKPDS patients' healthcare usage conducted in 1996-1997.
      RESULTS: Using the model, the estimate of the cost of first complications were as
      follows: amputation pound 8459 (95% confidence interval pound 5295, pound 13
      200); non-fatal myocardial infarction pound 4070 ( pound 3580, pound 4722); fatal
      myocardial infarction pound 1152 ( pound 941, pound 1396); fatal stroke pound
      3383 ( pound 1935, pound 5431); non-fatal stroke pound 2367 ( pound 1599, pound
      3274); ischaemic heart disease pound 1959 ( pound 1467, pound 2541); heart
      failure pound 2221 ( pound 1690, pound 2896); cataract extraction pound 1553 (
      pound 1320, pound 1855); and blindness in one eye pound 872 ( pound 526, pound
      1299). The annual average in-patient cost of events in subsequent years ranged
      from pound 631 ( pound 403, pound 896) for heart failure to pound 105 ( pound 80,
      pound 142) for cataract extraction. Non-in-patient costs for macrovascular
      complications were pound 315 ( pound 247, pound 394) and for microvascular
      complications were pound 273 ( pound 215, pound 343) in the year of the event. In
      each subsequent year the costs were, respectively, pound 258 ( pound 228, pound
      297) and pound 204 ( pound 181, pound 255). CONCLUSIONS: These results provide
      estimates of the immediate and long-term healthcare costs associated with seven
      diabetes-related complications.

PMID- 12786678
TI  - The vitamin D receptor gene variant and physical activity predicts fasting
      glucose levels in healthy young men.
AB  - AIMS: Vitamin D can influence lipolysis and insulin secretion. A common genetic
      polymorphism of the vitamin D receptor (VDR), which has been found to be
      associated with bone mineral density, has been reported to be also associated
      with Type 2 diabetes mellitus (DM). To test the influence of the VDR polymorphism
      on fasting glucose in healthy young men before the onset of Type 2 DM, we studied
      a homogeneous population of aircrew members. METHODS: A total of 1539 individuals
      were recruited during routine medical qualification for flying duty. Physical
      activity was assessed in all individuals and categorized into low physical
      activity (<or= 3 h per week) and high physical activity (> 3 h per week). The
      BsmI VDR polymorphism was analysed by polymerase chain reaction. On the day of
      blood testing the individuals were fasting for at least 8 h overnight. Serum
      glucose was measured within 60 min after sampling venous blood. RESULTS: In young
      males with low physical activity (n = 752) gene carriers with the VDR genotype BB
      (n = 137) have significantly (P < 0.001) higher levels of fasting glucose (5.61
      +/- 0.49 mmol/l) than gene carriers with the genotype Bb (n = 370; 5.44 +/- 0.44
      mmol/l) or bb (n = 245; 5.38 +/- 0.44 mmol/l). Of BB gene carriers, 47% had
      fasting glucose levels > 5.55 mmol/l compared with 36% of Bb gene carriers and
      34% of bb gene carriers (P = 0.018). This effect is absent in gene carriers with
      high physical activity (n = 787). CONCLUSIONS: The VDR genotype is associated
      with altered fasting glucose levels in young men with low physical activity. If
      this association is confirmed in other populations it might be worthwhile
      studying the particular benefits of an exercise programme in dependents of the
      VDR genotype.

PMID- 12786679
TI  - Relationship of lipoprotein(a) with intimal medial thickness of the carotid
      artery in Type 2 diabetic patients in south India.
AB  - OBJECTIVE: The objective of this study was to investigate the association of
      lipoprotein(a) [Lp(a)] levels with intimal medial thickness (IMT) in Type 2
      diabetic patients in south India. STUDY DESIGN: We studied 587 consecutive Type 2
      diabetic patients at the M.V. Diabetes Specialities Centre, Chennai. The mean age
      of the study group was 55 +/- 10 years and 71.2% were males. IMT of the right
      common carotid artery was determined using high-resolution B mode
      ultrasonography. Lp(a) levels were measured using ELISA. Since the frequency
      distribution of Lp(a) was skewed, Lp(a) values were log transformed and the
      geometric mean was used for statistical analysis. The tertiles of IMT were
      determined to analyse the association of Lp(a) and other factors with IMT.
      RESULT: The mean Lp(a) level in the study patients was 18.9 +/- 3.1 mg/dl
      (geometric mean +/- sd) and the mean IMT of the study subjects was 0.93 +/- 0.19
      mm (mean +/- sd). The prevalence of carotid atherosclerosis (defined as IMT > 1.1
      mm) among subjects with elevated Lp(a) levels > 20 mg/dl was significantly higher
      compared with those with Lp(a) levels </= 20 mg/dl (26.9% vs. 16.3%, P = 0.003).
      Lp(a) levels increased with increase in tertiles of IMT (anova, P < 0.05).
      Pearson correlation analysis of carotid IMT with other cardiovascular risk
      factors revealed strong correlation of IMT with age (P < 0.0001), duration of
      diabetes (P < 0.0001), systolic blood pressure (P < 0.0001), diastolic blood
      pressure (P = 0.006), LDL-cholesterol (P = 0.023), HbA1c (P = 0.017) and Lp(a) (P
      < 0.0001). Multiple logistic regression analysis showed age (P = 0.010), LDL
      cholesterol (P = 0.032) and Lp(a) (P = 0.021) to be associated with carotid
      atherosclerosis. CONCLUSION: The results suggest that Lp(a) has a strong
      association with IMT of carotid arteries in Type 2 diabetic subjects in south
      India.

PMID- 12786680
TI  - Comparison among different insulin sensitivity indices in obese patients.
AB  - AIMS: Recently, several indices have been proposed for the measurement of insulin
      sensitivity (IS). We set out to make a comparison between fasting insulin, and
      different IS indices in obese subjects. PATIENTS AND METHODS: Fasting and post
      load (75 g) glucose and insulin were measured in a consecutive series of 767 (626
      F, 141 M) obese (body mass index > 30 kg/m(2)) out-patients, with no known
      history of diabetes (DM). Mean (+/- sd) age was 46.7 +/- 13.8 years in females
      and 45.6 +/- 14.3 years in males. Indices of IS based on fasting homeostasis
      assessment model (HOMA) and post-load (ISI) glucose and insulin and either
      parameter (1A, and 1B scores) were determined. RESULTS: DM was diagnosed in 21.4%
      of females, and 20.6% of males, and impaired glucose tolerance in 24% females and
      21.3% males. Fasting and post-load glucose, triglyceride and HDL-cholesterol were
      correlated with all indices in both sexes (P < 0.05). The relative risk of
      different conditions in the upper quartile of ISI was similar to that observed in
      the upper quartile of HOMA. The HOMA index was similarly associated with low HDL
      cholesterol and hypertriglyceridaemia as fasting insulin, while it showed a
      greater association with diabetes; ISI was similarly associated with all three
      conditions as the HOMA index. CONCLUSIONS: Indices of IS based on fasting glucose
      and insulin show a greater association with diabetes, but not with other
      abnormalities related to insulin resistance, when compared with fasting insulin
      levels. Indices based on post-load glucose and insulin do not offer any advantage
      over those based on fasting values.

PMID- 12786681
TI  - The effectiveness of screening for diabetic retinopathy by digital imaging
      photography and technician ophthalmoscopy.
AB  - AIMS: To evaluate the introduction of a community-based non-mydriatic and
      mydriatic digital photographic screening programme by measuring the sensitivity
      and specificity compared with a reference standard and assessing the added value
      of technician direct ophthalmoscopy. METHODS: Study patients had one-field, non
      mydriatic, 45 degrees digital imaging photography prior to mydriatic two-field
      digital imaging photography followed by technician ophthalmoscopy. Of these
      patients, 1549 were then examined by an experienced ophthalmologist using slit
      lamp biomicroscopy as a reference standard. The setting was general practices in
      Gloucestershire. Patients were selected by randomizing groups of patients (from
      within individual general practices) and 3611 patients were included in the
      study. Patients for reference standard examination were recruited from groups of
      patients on days when the ophthalmologist was able to attend. The main outcome
      measure was detection of referable diabetic retinopathy (DR) as defined by the
      Gloucestershire adaptation of the European Working Party guidelines. RESULTS: For
      mydriatic digital photography, the sensitivity was 87.8%, specificity was 86.1%
      and technical failure rate was 3.7%. Technician ophthalmoscopy did not alter
      these figures. For non-mydriatic photography, the sensitivity was 86.0%,
      specificity was 76.7% and technical failure rate was 19.7%. CONCLUSIONS: Two
      field mydriatic digital photography is an effective method of screening for
      referable diabetic retinopathy. Non-mydriatic digital photography has an
      unacceptable technical failure rate and low specificity.

PMID- 12786682
TI  - Serum interleukin-6 levels and bone mineral density at the femoral neck in post
      menopausal women with Type 1 diabetes.
AB  - BACKGROUND: Although osteopenia is often reported in Type 1 diabetes mellitus,
      the pathogenic mechanisms are not fully understood. Oestrogen deficiency also
      leads to decreased bone mineral density (BMD). Enhanced interleukin-6 (IL-6)
      production among Type 1 diabetic patients could be involved in the pathogenesis
      of diabetic bone loss since it is a potent bone resorbing cytokine. AIMS: To
      evaluate the relationship between serum bioactive IL-6 levels and BMD at the
      femoral neck of post-menopausal women with Type 1 diabetes. METHODS: We studied
      BMD, urine excretion of deoxypirydynoline crosslinks, serum bioactive IL-6 and
      soluble IL-6 receptor (sIL-6R) levels in 20 post-menopausal women with Type 1
      diabetes mellitus, and compared these results with 20 matched healthy post
      menopausal controls. RESULTS: Post-menopausal women with Type 1 diabetes had
      significantly lower BMD at the femoral neck and increased serum bioactive IL-6
      levels compared with the control group, but no relationship was observed between
      these variables in a multiple regression analysis. Using BMD at the femoral neck
      of diabetic women as the dependent variable in the multiple step regression
      analysis model, we found that independent variables that were strongly associated
      with bone mass at the femoral neck in this group were: time since menopause and
      duration of diabetes. CONCLUSIONS: Although our study had a small sample size, we
      found that post-menopausal women with Type 1 diabetes mellitus present lower bone
      mass and higher serum bioactive IL-6 levels than matched healthy controls, but we
      were unable to find a correlation between these two parameters.

PMID- 12786683
TI  - Neuroglycopenia in normoglycaemic patients, and the potential benefit of ketosis.
AB  - We report a patient with recurrent symptoms of neuroglycopenia due to a defective
      glucose transport into brain. The potential benefit of ketosis in neuroglycopenia
      is discussed from the therapeutic concept of a ketogenic diet in GLUT1-deficiency
      syndrome.

PMID- 12786684
TI  - Adolescent onset Type 2 diabetes in a non-obese Caucasian patient with an
      unbalanced translocation.
AB  - BACKGROUND: Childhood onset Type 2 diabetes in the UK has been reported in obese,
      insulin-resistant subjects. Investigation is necessary to exclude other
      aetiologies including genetic causes. The co-existence of diabetes and a
      chromosomal breakpoint may indicate the position of novel diabetes genes. CASE
      REPORT: We describe a novel unbalanced translocation between Xq and 10p
      associated with amenorrhoea and onset of Type 2 diabetes in a non-obese Caucasian
      adolescent. There was no evidence of an autoimmune or known genetic aetiology for
      the diabetes and the phenotype was not typical of youth-onset Type 2. We
      therefore hypothesize that the translocation is implicated in the aetiology of
      the diabetes. This is supported by previous reports of diabetes as a feature of
      Xq deletions and Turner's syndrome and linkage to the Xq region in a genome-wide
      scan for Type 2 genes. CONCLUSION: That this region may harbour a gene
      predisposing to Type 2 diabetes and that cytogenetic studies may be useful in
      investigating diabetes in children and young adults.

PMID- 12786685
TI  - The association between satisfaction with services provided in primary care and
      outcomes in Type 2 diabetes mellitus.
AB  - BACKGROUND: Patient satisfaction is of increasing importance, is taken into
      account when planning services, and is used by healthcare providers as a measure
      of healthcare quality. Satisfaction with medical care, including diabetic care,
      has been associated with various health-related behaviours and outcomes that have
      a direct bearing on health and illness. The association between satisfaction and
      health outcomes is poorly understood. AIM: The aim of the study was to determine
      whether there is an association between satisfaction in patients with Type 2
      diabetes and the outcome of their diabetic care, and to determine the
      contribution of different aspects of satisfaction with the primary care. METHODS:
      Patients with Type 2 diabetes were identified from two general practices in
      Leeds. PATIENTS: scores on the General Practice Assessment Survey Questionnaire
      (GPAS) were correlated with the outcome of care, as measured by HbA1c level
      collected from patients' medical records. RESULTS: Data from 106 patients were
      analysed. There was a generally high satisfaction rate for all GPAS domains. The
      correlation between different GPAS domains and HbA1c level showed significant
      positive correlations (P < 0.001) for continuity of care, trust and overall
      satisfaction; and positive correlations (P < 0.01) for access, receptionists,
      interpersonal care, communication skills, knowledge of patient about the doctor,
      technical care, and practice nursing. CONCLUSION: The findings from this study
      demonstrate that there is an association between satisfaction and outcome in
      diabetes, which goes across all the GPAS domains. This suggests that processes
      that can act to increase patient satisfaction may be contributing to improved
      clinical outcomes. More development work is needed in this field to explore and
      elucidate the complex relationship between satisfaction and clinical outcomes.

PMID- 12786686
TI  - Studies of variability in the islet amyloid polypeptide gene in relation to Type
      2 diabetes.
AB  - AIMS: To explore whether the coding region of the islet amyloid polypeptide
      (IAPP) gene contains genetic variants associated with Type 2 diabetes and whether
      a previously reported association of the promoter variant -132g-->a with Type 2
      diabetes could be reproduced in Danish Caucasians. METHODS: The coding region was
      analyzed using single strand conformation polymorphism (SSCP) and heteroduplex
      analysis in 192 Type 2 diabetic patients. Restriction fragment length
      polymorphism (RFLP) was employed to screen for the promoter variant in 414 Type 2
      diabetic patients and 182 glucose-tolerant control subjects. RESULTS: The SSCP
      analysis identified an IVS+75a-->g variant in two patients. The frequency of
      heterozygous carriers of the promoter variant in the case-control study was 4.1%
      (17/414) and 7.1% (13/182), respectively. Odds ratio of the prevalence of Type 2
      diabetes in carriers compared with non-carriers was estimated to be 0.47 (95%
      confidence interval 0.19, 1.15). CONCLUSION: Neither variability in the coding
      region of the IAPP gene nor the -132g-->a promoter variant was associated with
      Type 2 diabetes among the studied Danish Caucasians.

PMID- 12786687
TI  - Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in
      Type 2 diabetic patients.
AB  - AIMS: To clarify if cardiovascular autonomic neuropathy is associated with
      carotid artery atherosclerotic plaques in Type 2 diabetic patients. METHODS:
      Cardiovascular autonomic nerve function was related to carotid artery ultrasound
      in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. RESULTS:
      Cardiovascular autonomic neuropathy [abnormal age corrected
      expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61
      (21%) patients. Patients with cardiovascular autonomic neuropathy showed
      increased degree of stenosis in the common carotid artery (24.6 +/- 13.2% vs.
      14.7 +/- 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 +/-
      1.7 vs. 3.2 +/- 1.6; P = 0.064). Controlled for age, AI correlated inversely with
      degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005),
      and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media
      thickness in the common carotid artery. In contrast, E/I ratio correlated only
      slightly with mean intima-media thickness in the common carotid artery (r = 
      0.28; P = 0.049). CONCLUSIONS: Cardiovascular autonomic neuropathy was associated
      with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios
      reflect efferent structural damage to parasympathetic nerves whereas abnormal AI
      reflects afferent autonomic dysfunction possibly due to impaired baroreceptor
      sensitivity secondary to carotid atherosclerosis.

PMID- 12786688
TI  - Insulin resistance Type A and short 5th metacarpals.
AB  - BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes
      and a variety of defects of insulin action. METHODS: We describe three members of
      an extended family spanning two generations with insulin resistance Type A and
      short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair
      distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic
      ovaries, diabetes, features of acromegaly, raised creatine kinase and
      triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal
      steroid and testosterone levels were normal. The proband's daughter had severe
      acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride,
      glucose and testosterone level short metacarpals and normal insulin receptor
      gene. The proband's son had a muscular build, raised creatine kinase,
      hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were
      normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and
      genetic syndromes associated with insulin resistance. This family was diagnosed
      as having insulin resistance Type A. This family does not conform entirely to any
      of the previously described syndromes and a number of family members have the
      phenotype of short 5th metacarpals, which appears to be associated with the
      features of insulin resistance Type A.

PMID- 12786689
TI  - Diabetes prevalence data for the United Kingdom--what do we have and what do we
      need?

PMID- 12786690
TI  - Poor pregnancy outcome for women with Type 2 diabetes.

PMID- 12786691
TI  - Symptoms reported during experimental hypoglycaemia: effect of method of
      induction of hypoglycaemia and of diabetes per se.

PMID- 12786692
TI  - Ambulatory blood pressure monitoring.

PMID- 12786697
TI  - Evidence-based review of the use of cryosurgery in treatment of basal cell
      carcinoma.
AB  - BACKGROUND: Cryosurgery has been used to treat basal cell carcinoma (BCC), and it
      has many technical advantages over other methods. It is therefore important to
      establish its efficacy as a treatment for BCC. OBJECTIVE: To review
      systematically the body of literature reporting on the efficacy of cryosurgery of
      BCC in terms of recurrence rates and cosmetic results. METHODS: A review is given
      of MEDLINE, EMBASE, CancerLit, and the Cochrane Database of Systematic Reviews
      for studies that examined cyosurgery in treatment of BCC patients. RESULTS: We
      found 13 noncontrolled prospective studies and 4 randomized clinical trials
      comparing cryosurgery to other methods of treatment for BCC. Because of the
      inability to double blind or placebo control treatment of BCC, none of the
      studies met criteria for A and B grade evidence, as defined by Sackett.
      Therefore, all studies were assigned grade C. CONCLUSIONS: According to the best
      evidence, recurrence rates of BCC treated with cryosurgery are low (less than
      10%). Except in one study, recurrence rates are calculated based on clinical,
      rather than histologic diagnosis, which may cause the rates to appear somewhat
      lower than they actually are, especially with a short follow-up period. Cosmetic
      results of cryosurgery treatment reported in literature are described as good by
      most investigators. Overall, there are sufficient data to consider cryosurgery as
      a reasonable treatment for BCC. There are no good studies, however, comparing
      cryosurgery with other modalities, particularly with Mohs surgery, excision, or
      electrodessication and curretage so that no conclusion can be made whether
      cryosurgery is as efficacious as other methods. Also, there is no evidence on
      whether curetting the lesions before cryosurgery affects the efficacy of
      treatment.

PMID- 12786698
TI  - Getting started with evidence-based research.

PMID- 12786699
TI  - Soft tissue augmentation with artecoll: 10-year history, indications, techniques,
      and complications.
AB  - Most of the biologic filler materials that increase the thickness of the corium
      in a wrinkle line are phagocytosed within a certain time. Therefore, a lasting
      effect can only be achieved with nonresorbable synthetic substances. Artefill
      consists of 20 volume percent microspheres of polymethyl-methacrylate and 80
      volume percent of bovine collagen. Beneath the crease, the microspheres with
      their exceptional surface smoothness stimulate fibroblasts to encapsulate each
      individual one of the 6-million microspheres contained in 1 mL of Artefill.
      Collagen is merely a carrier substance that prevents the microspheres from
      agglomerating during tissue ingrowth. The 20 volume percent of microspheres in
      Artefill provides the scaffold for the 80% volume of connective tissue
      deposition, a complete replacement of the injected collagen. The filler material
      beneath a crease acts like a splint and prevents the possibility of its further
      folding, thereby allowing the diminished thickness of the corium in a crease to
      recover. This recovery process is well known even in older patients with facial
      paralysis or after a stroke, whose facial wrinkles and furrows on the paralyzed
      side disappear over time.

PMID- 12786700
TI  - A randomized, double-blind, multicenter comparison of the efficacy and
      tolerability of Restylane versus Zyplast for the correction of nasolabial folds.
AB  - BACKGROUND: Bovine collagen is extensively used for facial soft tissue
      augmentation but provides only temporary correction and can cause
      hypersensitivity reactions. Hyaluronic acid derivatives potentially offer
      improved longevity of correction and a reduced risk of immunogenicity and
      hypersensitivity. OBJECTIVE: To compare the efficacy and safety of nonanimal
      stabilized hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) with that of
      bovine collagen (Zyplast) for treatment of nasolabial folds. METHODS: One hundred
      thirty-eight patients with prominent nasolabial folds were randomized to
      treatment with hyaluronic acid gel and bovine collagen on contralateral sides of
      the face. Treatments were repeated at 2-week intervals, as required, to achieve
      "optimal cosmetic result" (baseline). Outcomes were evaluated by a blinded
      investigator at 2, 4, and 6 months after baseline. RESULTS: Less injection volume
      was required for "optimal cosmetic result" with hyaluronic acid gel than with
      bovine collagen, and patients and investigators judged hyaluronic acid gel to be
      more effective in maintaining cosmetic correction. The investigator-based Wrinkle
      Severity Rating Scale and Global Aesthetic Improvement Scale assessments at 6
      months after baseline indicated that hyaluronic acid gel was superior in 56.9%
      and 62.0% of patients, respectively, whereas bovine collagen was superior in 9.5%
      and 8.0% of patients, respectively. The frequency, intensity, and duration of
      local injection-site reactions were similar for the two products. CONCLUSION:
      Nonanimal stabilized hyaluronic acid provides a more durable aesthetic
      improvement than bovine collagen and is well tolerated.

PMID- 12786701
TI  - 308-nm Excimer laser treatment of mature hypopigmented striae.
AB  - BACKGROUND: The 308-nm excimer laser has been shown to be effective in the
      treatment of disorders of hypopigmentation. OBJECTIVE: To evaluate the
      effectiveness of the 308-nm excimer laser in the treatment of mature
      hypopigmented striae. RESULTS: Seventy-five subjects were treated for a total of
      615 treatments. All patients achieved a substantial increase in the darkening of
      their striae after an average of 8.4 treatments. Clinically evident improvement
      in cosmetic appearance of striae was noted by 80% of subjects. CONCLUSION: The
      308-nm excimer laser is effective for increasing pigmentation in mature
      hypopigmented striae. This pigmentation is cosmetically significant. Future
      studies are required to determine the duration of clinical improvement.

PMID- 12786702
TI  - Objective and quantitative improvement of rosacea-associated erythema after
      intense pulsed light treatment.
AB  - BACKGROUND: Despite the widespread and quite successful use of various lasers and
      light sources to treat facial erythema, the literature contains little, if any,
      objective and quantitative improvement. In addition, very few studies
      specifically address rosacea-associated erythema. OBJECTIVE: To assess
      quantitatively the degree of improvement in patients with rosacea after intense
      pulsed light treatment. The three main parameters that were objectively measured
      were blood flow, telangiectasia, and erythema. METHODS: Four patients with
      rosacea-associated erythema and telangiectasia were treated five times at 3-week
      intervals with the Photoderm VL (Lumenis, Needham, MA). The 515-nm filter, a
      single pulse duration of 3 ms, and various fluences were used. Blood flow was
      measured by the scanning laser Doppler. Close-up photography ensured
      reproducibility and enabled quantification of telangiectasia and erythema by
      subsequent computer image analysis. Measurements were taken at baseline and at 1
      month after the last treatment. RESULTS: The scanning laser Doppler demonstrated
      a 30% decrease in blood flow (P<0.05). A 29% decrease in actual area of the cheek
      occupied by telangiectasia was noted (P<0.05). A 21% decrease in the intensity of
      erythema was noted (P<0.05). CONCLUSION: As demonstrated by truly objective and
      quantitative means, intense pulsed light is effective for reducing rosacea
      associated blood flow, telangiectasia, and erythema.

PMID- 12786703
TI  - Microresurfacing using the variable-pulse erbium:YAG laser: a comparison of the
      0.5- and 4-ms pulse durations.
AB  - BACKGROUND: Laser resurfacing has become less popular because of its long
      recovery time, significant discomfort, and potential risks. Microsurfacing
      employs the use of single-pass erbium:YAG (Er:YAG) "mini peels," which may be
      performed serially. OBJECTIVE: The purpose of this study was to evaluate the
      efficacy and patient acceptance of microresurfacing Er:YAG peels in treating
      facial photodamage. The variable-pulse Er:YAG system was used and was allowed a
      comparison of the 0.5- and 4-ms pulse widths. METHODS: Six female patients
      underwent eight microresurfacing peels in a split-face fashion using the 0.5- and
      4.0-ms pulse durations of a variable-pulse Er:YAG laser. Patients returned at
      postoperative Days 3 to 4 and 7 for clinical evaluation and Mexameter
      measurements. RESULTS: There were no significant differences in healing or
      postoperative erythema between the 0.5- and 4-ms pulse durations on postoperative
      Day 7. The average time to reepithelialization was 3.6 days. In a 1-year
      postoperative interview, four of six patients said that they would undergo the
      peel again periodically, and five of six stated they had maintained some level of
      improvement. CONCLUSION: Microresurfacing is an effective and well-tolerated
      procedure. Benefits include its tolerability under topical anesthesia, limited
      down time, and high patient satisfaction.

PMID- 12786704
TI  - Comparative trial between sodium tetradecyl sulfate and glycerin in the treatment
      of telangiectatic leg veins.
AB  - BACKGROUND: Thirteen patients were treated with either sodium tetradecyl sulfate
      (STS) or glycerin to compare the efficacy and adverse sequelae of each agent.
      OBJECTIVE: To determine the relative safety and efficacy of two sclerosant
      solutions. METHODS: Each patient's leg veins that were from 0.2 to 0.4 mm in
      diameter and that did not have incompetence from the saphenofemoral junction and
      whose feeding reticular veins had been already treated in a prior sclerotherapy
      session were randomly treated with either 0.25% STS or 72% glycerin solution.
      Patients were evaluated from 2 to 6 months postsclerotherapy for overall clinical
      improvement and incidence of adverse sequelae. RESULTS: Glycerin was comparable
      to STS in discomfort of injection but demonstrated a significant decrease in
      bruising, swelling, and postprocedural hyperpigmentation. Glycerin also
      demonstrated a better, more rapid clearance of treated telangiectasias.
      CONCLUSIONS: Seventy-two percent glycerin is a safe and effective sclerosant with
      fewer side effects and more rapid clearance of telangiectatic leg veins than STS.

PMID- 12786705
TI  - Transilluminated powered phlebectomy: advantages and disadvantages of a new
      technique.
AB  - BACKGROUND: Transilluminated powered phlebectomy is a new procedure for minimal
      invasive varicose vein surgery. OBJECTIVE: To evaluate this technique for its
      benefit and the technique-related risks and complications. METHODS: Thirty
      patients were prospectively operated with this new technique by the same surgeon
      (11 of them bilaterally [41 legs in all]). According to the sonography, sapheno
      femoral-junction ligation and stripping of the long saphenous vein were done if
      necessary. The phlebectomy of the side branches was done with the new system
      (Trivex System/Smith and Nephew). The postoperative follow-up was at 10 days and
      6 weeks. RESULTS: There was no intraoperative complication. The mean operation
      time per leg was 40 minutes. Twenty-five patients had an uneventful postoperative
      course. Twenty two have been very satisfied with the cosmetically result. Two
      patients required reoperation because of postoperative hematoma. One patient
      developed a seroma, which could be managed via puncture. One patient developed
      persistent brown scar. The overall morbidity was 12.2%. CONCLUSION: Using
      transilluminated powered phlebectomy, multiple and large incisions could be
      reduced. A perfect cosmetic outcome might be reached if the surgeon is aware of
      technique-related complications. To evaluate the real value of this technique,
      further randomized trials are necessary.

PMID- 12786706
TI  - Topical antibacterial agents for wound care: a primer.
AB  - Although often overlooked, topical antibiotic agents play an important role in
      dermatology. Their many uses include prophylaxis against cutaneous infections,
      treatment of minor wounds and infections, and elimination of nasal carriage of
      Staphylococcus aureus. For these indications, they are advantageous over their
      systemic counterparts because they deliver a higher concentration of medication
      directly to the desired area and are less frequently implicated in causing
      bacterial resistance. The ideal topical antibiotic has a broad spectrum of
      activity, has persistent antibacterial effects, and has minimal toxicity or
      incidence of allergy.

PMID- 12786707
TI  - Lidocaine iontophoresis for local anesthesia before shave biopsy.
AB  - BACKGROUND: Lidocaine iontophoresis is a method of topical anesthesia in which
      lidocaine is driven into the skin under the influence of electric current.
      OBJECTIVE: To compare lidocaine iontophoresis to placebo for topical anesthesia
      before shave biopsy in adult patients. METHODS: This was a single-center, double
      blind, placebo-controlled evaluation of iontophoresis of 2% lidocaine with
      1:100,000 epinephrine in patients undergoing shave biopsy. Patients were
      evaluated for sensation to pinprick after iontophoresis. After completion of the
      procedure, those patients who did not receive supplemental lidocaine rated the
      pain associated with the procedure using a 10-cm visual analog scale. The
      investigator also evaluated the patient's pain after biopsy. Treatment sites were
      examined for evidence of adverse events such as erythema, urticaria, or burns.
      RESULTS: Forty-one patients undergoing shave biopsy for evaluation of skin
      lesions were enrolled. Nineteen of 21 patients in the lidocaine group versus 2 of
      20 placebo patients required no supplemental anesthesia (P<0.001). The pain
      reported by the patient on the visual analog scale subsequent to the procedure
      was significantly lower in the lidocaine group (P<0.001). In concordance with the
      results reported by the patients, investigators rated pain lower in the lidocaine
      group (P<0.001). Blanching and/or erythema occurring at the iontophoresis-treated
      site in 37 of 41 patients resolved within 1 hour. There were no other treatment
      related events. CONCLUSIONS: Lidocaine iontophoresis is a safe and effective
      method of administering topical anesthesia before shave biopsy in adult patients.

PMID- 12786708
TI  - A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours
      and is visualized by light microscopy.
AB  - BACKGROUND: In chronic wounds, biofilms probably play a vital role in protecting
      bacteria from host defenses and antimicrobial medications by creating a barrier
      of exopolysaccharide that is difficult for the immune system and antibiotics to
      penetrate. A biofilm consists of an exopolysaccharide matrix that is produced and
      secreted by certain species of bacteria. OBJECTIVE: The purpose of this study was
      to visualize and time the progressing growth of a biofilm by a wound-isolated
      Pseudomonas aeruginosa. METHODS: P. aeruginosa that was initially isolated from a
      human burn wound was allowed to grow a biofilm in vitro. We used a modified Congo
      red staining technique to demonstrate the sequential development of a mature
      biofilm as examined by light microscopy. RESULTS: We show that the
      exopolysaccharide of the developing biofilm is visible in just 5 hours after
      inoculation and has the characteristics of a mature biofilm by 10 hours.
      CONCLUSION: The rapidity of biofilm growth suggests that bacteria in wounds
      possess the capacity of producing this shield against antibiotics and immune
      effector cells early in the infection process. Therefore, efforts to prevent or
      slow the proliferation of bacteria and biofilms should occur soon after a wound
      is created. Additionally, this staining technique can be used to demonstrate the
      ability of agents to slow biofilm growth or to interrupt formed biofilm and may
      be useful in future studies of chronically infected wounds.

PMID- 12786709
TI  - A simple technique for repair of Cupid's bow.
AB  - BACKGROUND: Reconstruction of the upper lip is among the most challenging
      problems faced by Mohs surgeons. Cupid's bow, with its marked variability among
      individuals, can be particularly difficult to recreate. Numerous complex
      reconstructive methods have been described in the literature. The authors present
      a novel technique for aesthetic reconstruction of Cupid's bow. METHODS:
      Retrospective case reviews of defects resulting from Mohs excision located at or
      near Cupid's bow are given. Repair was performed using our modified mucosal
      advancement flap technique. RESULTS: Acceptable or very good cosmesis was
      attained in all cases. CONCLUSION: The use of our simple modification of the
      mucosal advancement flap allows aesthetic reconstruction of Cupid's bow in select
      cases. Selection criteria for defects amenable to this technique are presented.

PMID- 12786710
TI  - Treatment of phacomatosis pigmentovascularis: a combined multiple laser approach.
AB  - BACKGROUND: Phacomatosis pigmentovascularis (PPV) consists of a capillary
      malformation with a variety of melanocytic lesions, which involve various regions
      of the body and are difficult to treat with conventional therapeutic tools.
      OBJECTIVE: We described two cases with PPV (type IIa and IIb) that were
      successfully treated with different lasers. METHODS: The areas involved by both
      melanocytic lesions and port-wine stains were treated using the Q-switched ruby
      laser, the Q-switched Alexandrite laser, and the flashlamp pumped pulsed-dye
      laser. RESULTS: Removal of a good portion of cutaneous and vascular lesions using
      combined multiple laser approach was achieved after 6 sessions in the first case
      under general anesthesia and after 31 sessions under local anesthesia in the
      second case. CONCLUSION: PPV type II can be treated successfully by laser
      treatment. We prefer to start combined multiple laser treatment of PPV in
      childhood period under general anesthesia because it will reduce the number of
      treatment, improve the patient's quality of life, and increase the cost
      effectiveness of the treatment.

PMID- 12786711
TI  - Recurrent adenoid cystic carcinoma of the scalp treated with mohs micrographic
      surgery.
AB  - Primary cutaneous adenoid cystic carcinoma is a rare skin neoplasm with a high
      potential for recurrence after local excision. We present a case of a 45-year-old
      white female with recurrent primary cutaneous adenoid cystic carcinoma of the
      scalp. The tumor was resected with Mohs surgery in two stages and defect repaired
      with split-thickness skin graft. There has been no recurrence of the tumor in the
      12-month follow-up period.

PMID- 12786712
TI  - Metastatic basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma is the most common malignancy of humans.
      Although it is axiomatic that this tumor does not evolve into metastatic disease,
      such events rarely occur, and this possibility should not be overlooked.
      OBJECTIVES: The reader should better understand the sequence of events that
      resulted in metastatic disease and how these events are emblematic of the rare
      cases of basal cell carcinoma that systemically spread. METHODS: We present a
      case report of basal cell carcinoma that underwent distant metastasis. A short
      review of the literature is included. RESULTS: Although basal cell carcinoma is
      commonly considered a regional tumor with virtually no propensity for distant
      spread, this case reveals that metastatic disease does occur and with devastating
      results. CONCLUSION: Metastatic disease in basal cell carcinoma is a very rare
      but catastrophic consequence of this very common skin malignancy.

PMID- 12786713
TI  - Radical resection of giant congenital melanocytic nevus and reconstruction with
      meek-graft covered integra dermal template.
AB  - BACKGROUND: Giant congenital melanocytic nevi represent a surgical challenge,
      particularly in cases in which the size of the nevus exceeds certain extend and
      malignant transformations have to be considered. OBJECTIVE: To discuss through
      case report considerable surgical options when extensive giant congenital
      melanocytic nevi with malignant transformation are encountered. METHODS: We
      present an unusual case of a giant congenital melanocytic nevi of the entire back
      of a 44-year-old patient. To achieve radical resection with direct appropriate
      wound closure and acceptable outcome, the integument of the entire back was
      excised and covered with Integra, followed by split-thickness skin grafting after
      stable integration of the matrix. RESULTS: The approach resulted in a complete
      excision of the tumor and acceptable cosmetic and excellent biomechanical
      outcome. CONCLUSION: The introduced practice demonstrates a useful alternative to
      established methods, particularly if tumor excision in large areas and subsequent
      wound closure might be achieved in one procedure.

PMID- 12786714
TI  - Repair of a large wound of the back, post-Mohs micrographical excision, using
      chronic skin expansion.
AB  - BACKGROUND: Large defects not otherwise closed primarily may be closed after
      chronic skin expansion. OBJECTIVE: If chronic expansion were deemed indicated for
      the closure of a proposed defect expected to result from Mohs micrographic
      surgery, can it be performed before Mohs surgery, avoiding the increased chance
      of expander extrusion via the defect when done postoperatively? METHODS: A team
      approach of a Mohs surgeon and a plastic surgeon coordinated scheduling an
      insertion of and staged infiltration of a tissue expander before Mohs surgical
      removal of a large basal cell carcinoma on the back of a young woman. The
      reconstruction after Mohs surgery was scheduled for the immediate postoperative
      period. RESULTS: The Mohs surgery completed removed the carcinoma, and the
      expander was removed, enabling the surgeon to perform a side-to-side closure.
      CONCLUSION: Provided that there is not a great probability of the neoplasm
      extending significantly deeper or wider than expected and that the skin expander
      is placed so as not to disturb the plane of Mohs excision, this is a useful
      technique to close large Mohs defects.

PMID- 12786715
TI  - Vulvar squamous cell carcinoma metastatic to skin of the forearm.

PMID- 12786716
TI  - Immediate local and regional recurrence after the excision of a polypoid
      melanoma: tumor dormancy or tumor activation?
AB  - Recurrent melanoma occurs in approximately one third of the patients who are
      treated for cutaneous melanoma. Although the majority of recurrences occur within
      the first few years of primary therapy, a significant number remain at risk
      beyond 10 years. Tumor dormancy provides the conceptual framework to explain a
      prolonged quiescent state in which tumor cells are present, but tumor progression
      is not clinically apparent. Surgery, or other perturbing factors, might modulate
      the transition of dormant cancer cells to rapidly growing ones. These may be due
      to a perturbation of the mechanisms of tumor regulation such as local immunity or
      angiogenesis. Here, the case of a woman is discussed in whom the surgical removal
      of a polypoid melanoma was followed, in less than a month, by local recurrence
      and locoregional lymph nodal metastases, which were previously clinically absent.

PMID- 12786717
TI  - Sclerotherapy of hemangioma with late involution.
AB  - BACKGROUND: Most cutaneous hemangiomas involute spontaneously. However, the
      lesion existing on the face poses a cosmetic problem during the waiting period
      for involution. METHODS: Hemangioma showing late involution was treated by local
      injection of monoethanolamine oleate solution. RESULTS: The lesion flattened and
      was excised serially. CONCLUSION: Sclerotherapy with monoethanolamine oleate can
      shorten the waiting period for involution and can decrease the risk of
      psychosocial trauma. Moreover, it provides good preparation for further surgery.
      Such sclerotherapy is effective in the treatment of hemangioma with late
      involution.

PMID- 12786718
TI  - Revisiting the purse-string closure: some new methods and modifications.
AB  - BACKGROUND: Surgical wounds resulting from the extirpation of cutaneous
      malignancies can be repaired in a number of ways. One alternative, which has been
      used extensively in our practice, is the purse-string closure. This method of
      closure offers distinct advantages in the proper setting over traditional methods
      of closure. OBJECTIVE: Over the years, our approach to this procedure has
      evolved, and we have integrated a number of new modifications that are presented
      later here. METHODS: A report of three illustrative cases is given. RESULTS:
      Three cases are presented that illustrate some new modifications to the purse
      string closure. CONCLUSION: The purse-string closure, which uses circumferential
      tissue advancement, can be used to close a wide range of surgical wounds. This
      method also frequently offers the advantage of an excellent cosmetic outcome.

PMID- 12786719
TI  - Response of elastosis perforans serpiginosa to pulsed CO2, Er:YAG, and dye
      lasers.

PMID- 12786720
TI  - Contamination by nickel, copper and zinc during the handling of euro coins.
AB  - The introduction of the euro has revived interest in the risk of nickel allergy
      due to the handling of coins. In the present work, the transfer of metallic
      contamination during the manipulation of coins is examined by means of leaching
      experiments and manipulation tests. It is shown that pre-existing metallic
      species present on the surface of the coins are the major source of contamination
      during manipulation, and that friction inherent to everyday usage contributes
      predominantly to their transfer to the hands. The comparison of coins as to their
      relative risks of metal contamination should therefore rely on tests that
      simulate the friction inherent in everyday human handling. Carrying out such
      tests with the newly issued 1 euro and 2 euro pieces, we find, contrary to long
      term leaching measurements, that the euros release less nickel than previously
      circulated pure-nickel coins, but that this decrease is less pronounced than
      might have been hoped for on the basis of their surface composition. When the
      coins are rubbed to a shiny polish before manipulation, contamination of the
      fingers is reduced by more than a factor of 10. A comparison of coins used in
      France indicates that the introduction of the common currency has led to a
      fourfold reduction in contamination by nickel, while causing a 45% increase in
      contamination by copper.

PMID- 12786721
TI  - Career counsellors and occupational contact dermatitis.
AB  - Career counsellors are in a unique position to provide timely preventive advice
      to young people at risk of developing occupational contact dermatitis. Career
      counsellors need to be aware of risk factors for this condition, including atopic
      eczema, and of high-risk occupations, such as hairdressing. A cross-sectional
      survey of 82 career counsellors was conducted at an Australian career
      counsellors' conference. 24 (29%, 95% confidence interval (95% CI) 19-40%)
      correctly identified eczema as a risk factor. 25 (30%, 95% CI 21-41%) indicated
      consideration of past skin problems during career counselling. 30 (36%, 95% CI 25
      47%) correctly reported at least 1 high-risk occupation, with hairdressing being
      most frequently identified. Only 3 of the 82 (4%, 95% CI 0-7%) correctly answered
      all 3 questions.

PMID- 12786722
TI  - Use of in vitro release of interferon-gamma in the diagnosis of contact allergy
      to potassium dichromate - a controlled study.
AB  - The use of in vitro release of interferon-gamma (IFN-gamma) in the diagnosis of
      contact allergy to potassium dichromate was studied in 20 patients who had
      positive patch tests to chromate and in 30 control subjects (10 patients with
      contact dermatitis, allergic to other allergens, 10 patients with other
      dermatologic diseases and 10 healthy subjects). The release of IFN-gamma in the
      supernatants of the peripheral blood lymphocytes was significantly higher in the
      patients with proven allergy to chromate (P = 0.001). Further studies are needed
      to determine if IFN-gamma release may serve as an additional diagnostic tool in
      contact dermatitis.

PMID- 12786723
TI  - The role of 3-dimethylaminopropylamine and amidoamine in contact allergy to
      cocamidopropylbetaine.
AB  - Since it has been found that all subjects with contact allergy to
      cocamidopropylbetaine (CAPB) have positive reactions to 3
      dimethylaminopropylamine (DMAPA), and reports have appeared in literature of the
      sensitizing action of amidoamine in products containing CAPB, we aimed to verify
      the possibility that pure amidoamine may have a sensitizing role in subjects with
      positive reactions to CAPB. To this end, in 10 patients with contact allergy to a
      commercial CAPB, we tested DMAPA 1% aq. and a pure amidoamine in concentrations
      ranging from 0.5% aq. to 0.1% aq. The study showed that all patients with
      positive reactions to DMAPA reacted to amidoamine at 0.5% and 0.25% aq., while 4
      of the 10 also had positive reactions to amidoamine at 0.1% aq. We consider that
      simultaneous allergic reaction to DMAPA and amidoamine represents cross
      reactivity and hypothesize that DMAPA is in fact the true sensitizing substance,
      while amidoamine, which may in any case release DMAPA in vivo as a result of
      enzymatic hydrolysis, may favour the transepidermal penetration of the
      sensitizing agent. In addition, we advise that testing of CAPB be suspended,
      because, as suggested by chemico-structural analyses and demonstrated in vivo,
      when thoroughly purified, it no longer has a sensitizing action.

PMID- 12786724
TI  - Presence of formaldehyde in topical corticosteroid preparations available on the
      Swedish market.
AB  - The aim of this study was to investigate the formaldehyde content of topical
      corticosteroid preparations available on the Swedish market. 73 samples were
      analysed with the chromotropic acid (CA) method for semi-quantitative
      formaldehyde determination and 30 samples with a high-performance liquid
      chromatographic method. These included 24 ointments, 28 creams, 1 lotion, 6
      liniments, 2 gels, 9 solutions, 2 mousses and 1 oral paste. Formaldehyde was
      found in 5 creams and 1 ointment. Sources of formaldehyde in these preparations
      were discussed. Isopropanol was identified as a probable source of yellow
      discoloration, leading to false-negative results with the CA method.

PMID- 12786725
TI  - Papular dermatitis and a persistent patch test reaction to gold sodium
      thiosulfate.
AB  - The role of gold in allergic contact dermatitis is poorly understood and is a
      subject of increasing interest. Recent studies demonstrate that gold-positive
      patch testing is not uncommon, but persistent patch test reactions are rarely
      reported. We present a case of a 53-year-old woman with a 7-year history of a
      scattered, pruritic papular dermatitis. Patch testing demonstrated a persistent,
      positive reaction to gold sodium thiosulfate. The histopathology of the patch
      test site and that of the cutaneous eruption were similar in nature but differing
      in severity. No other allergens have been identified, but gold avoidance has not
      yet resulted in the clearing of her eruption. This case underscores the
      difficulty in making a clinical correlation despite suggestive clinical
      pathologic evidence.

PMID- 12786726
TI  - Patch testing with zinc dibenzyldithiocarbamate. A multicentre study of the
      Information Network of Departments of Dermatology and the German Contact
      Dermatitis Research Group.

PMID- 12786727
TI  - Airborne contact dermatitis from Ambrosia deltoidea (triangle-leaf bursage).
AB  - 3 cases of contact dermatitis due to exposure to airborne allergens from Ambrosia
      deltoidea (triangle-leaf bursage) are presented. Although airborne plant
      dermatitis was suggested in each case by a history of aggravation of the rash by
      outdoor exposure and typical skin lesions, patch testing with an oleoresinous
      extract of A. deltoidea leaves identified the source of the sensitizer, not
      previously reported. As A. deltoidea is a ragweed that probably contains
      sesquiterpene lactones nearly identical to those of ragweeds widely prevalent in
      most of North America, the patients presented indicate the need for commercially
      available, standardized, plant extracts for patch testing in this country. The
      finding of positive patch tests with filters from an air sampler placed in 1
      patient's domestic environment suggests a new avenue of investigation in airborne
      contact dermatitis.

PMID- 12786728
TI  - Deodorants: an experimental provocation study with hydroxycitronellal.
AB  - Axillary dermatitis is a common problem, particularly in individuals with contact
      allergy to fragrances. Many individuals suspect their deodorant to be the causal
      product of their fragrance allergy. It has been shown that deodorants containing
      cinnamic aldehyde (cinnamal) can elicit axillary dermatitis in patients
      sensitized to this substance. The aim of the present investigation was to
      evaluate the importance of hydroxycitronellal used in deodorants for the
      development of axillary dermatitis, when applied by individuals with and without
      contact allergy to this fragrance chemical. Patch tests with deodorants and
      ethanolic solutions containing hydroxycitronellal, as well as repeated open
      application tests (ROAT) with roll-on deodorants with and without
      hydroxycitronellal at different concentrations, were performed in 14 dermatitis
      patients, 7 with and 7 without contact allergy to hydroxycitronellal. A positive
      ROAT was noted only in the patients hypersensitive to hydroxycitronellal (P <
      0.001) and only in the axilla to which the deodorants containing
      hydroxycitronellal had been applied (P < 0.001). Deodorants containing
      hydroxycitronellal in the concentration range of 0.032-0.32% used twice daily on
      healthy skin in individuals hypersensitive to hydroxycitronellal can elicit
      axillary dermatitis in a few weeks.

PMID- 12786729
TI  - Contact allergy to propylene glycol in brassiere padding inserts.

PMID- 12786730
TI  - Allergic contact dermatitis from 1,6-hexamethylene diisocyanate in a domestic
      setting.

PMID- 12786731
TI  - Clinically relevant contact urticaria caused by Thrombocid ointment.

PMID- 12786732
TI  - Allergic contact dermatitis in methotrexate manufacture.

PMID- 12786733
TI  - Contact allergens in 200 patients with hand dermatitis.

PMID- 12786734
TI  - Contact allergy to tetrahydrocurcumin.

PMID- 12786735
TI  - Allergic contact dermatitis from propylene glycol ricinoleate in a lipstick.

PMID- 12786736
TI  - Recurrent facial dermatitis from chamomile tea.

PMID- 12786737
TI  - Occupational allergic contact dermatitis from 1,2-benzisothiazolin-3-one without
      cross-sensitization to other isothiazolinones.

PMID- 12786738
TI  - Allergic contact cheilitis from D&C Red no 7 in lipstick.

PMID- 12786739
TI  - Contact dermatitis in the elderly.

PMID- 12786740
TI  - Contact dermatitis due to alkyl diaminoethylglycine hydrochloride.

PMID- 12786741
TI  - Baboon syndrome due to pseudoephedrine.

PMID- 12786742
TI  - Coccygeal pad.

PMID- 12786743
TI  - Red tattoo reactions.

PMID- 12786744
TI  - Contact urticaria syndrome from occupational triphenyl phosphite exposure.

PMID- 12786745
TI  - Palpebral eczema due to contact allergy to henna used as a hair dye.

PMID- 12786748
TI  - The molecular genetics of Usher syndrome.
AB  - Association of sensorineural deafness and progressive retinitis pigmentosa with
      and without a vestibular abnormality is the hallmark of Usher syndrome and
      involves at least 12 loci among three different clinical subtypes. Genes
      identified for the more commonly inherited loci are USH2A (encoding usherin),
      MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding
      protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and
      USH1G (encoding SANS). Transcripts from all these genes are found in many
      tissues/cell types other than the inner ear and retina, but all are uniquely
      critical for retinal and cochlear cell function. Many of these protein products
      have been demonstrated to have direct interactions with each other and perform an
      essential role in stereocilia homeostasis.

PMID- 12786749
TI  - Development of the thyroid gland: lessons from congenitally hypothyroid mice and
      men.
AB  - Congenital hypothyroidism is the most common congenital endocrine disorder (one
      newborn in 3000) and represents the most common cause of preventable mental
      retardation. In 10-20% of cases, it is due to autosomal recessive functional
      disorders leading to goiter formation (thyroid dyshormonogenesis). In the
      remainder, it is due to thyroid dysgenesis, which comprises usually isolated
      defects in: (1) migration of the median thyroid anlage, leading to a round
      cluster of ectopic cells (usually in a sublingual position) with no other thyroid
      tissue present; (2) differentiation or survival of the thyroid follicular cells
      leading to athyreosis; and (3) growth of a thyroid with the normal bilobed shape
      and in the normal cervical position (orthotopic hypoplasia). Mouse knock-outs
      have demonstrated that thyroid transcription factor-1 (TTF-1) and PAX8 are
      required for the survival and proliferation of thyroid follicular cell
      precursors, TTF-2 for their downward migration and the thyrotropin receptor
      (TSHR) for post-natal thyroid growth. In humans, thyroid dysgenesis is generally
      a sporadic malformation but an affected relative is found in 2% of cases, a
      figure 15-fold higher than by chance alone. Pedigree analysis is most compatible
      with dominant inheritance with variable penetrance. However, mutations in TTF-1,
      TTF-2, PAX8 and TSHR are found in <10% of patients with congenital hypothyroidism
      and these predominantly have orthotopic thyroid hypoplasia, often associated with
      other malformations. This low yield and the discordance of >90% of monozygotic
      twin pairs suggests that isolated thyroid ectopy or athyreosis most often results
      from early somatic mutations, epigenetic modifications or stochastic
      developmental events.

PMID- 12786753
TI  - Predictive, pre-natal and diagnostic genetic testing for Huntington's disease:
      the experience in Canada from 1987 to 2000.
AB  - Predictive and pre-natal testing for Huntington's Disease (HD) has been available
      since 1987. Initially this was offered by linkage analysis, which was surpassed
      by the advent of the direct mutation test for HD in 1993. Direct mutation
      analysis provided an accurate test that not only enhanced predictive and pre
      natal testing, but also permitted the diagnostic testing of symptomatic
      individuals. The objective of this study was to investigate the uptake,
      utilization, and outcome of predictive, pre-natal and diagnostic testing in
      Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian
      medical genetics centres and their affiliated laboratories offering genetic
      testing for HD were invited to participate. A total of 15 of 22 centres (68.2%),
      currently offering or ever having offered genetic testing for HD, responded,
      providing data on test results, demographics, and clinical history. A total of
      1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were
      performed. The uptake for predictive testing was approximately 18% of the
      estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to
      20.7% in British Columbia. There appears to have been a decline in the rate of
      testing in recent years. Of the predictive tests, 45.0% of individuals were found
      to have an increased risk, and a preponderance of females (60.2%) sought testing.
      A greater proportion of those at < or = 25% risk sought predictive testing once
      direct CAG mutation analysis had become available (10.9% after mutation analysis
      vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were
      requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in
      termination of pregnancy in all but one. Diagnostic testing identified 68.5% of
      individuals to be positive by mutation analysis, while 31.5% of those with HD
      like symptoms were not found to have the HD mutation. The positive diagnostic
      tests included 24.5% of individuals with no known prior family history of HD.

PMID- 12786754
TI  - Analysis of splice-site mutations of the alpha-galactosidase A gene in Fabry
      disease.
AB  - Fabry disease is an X-linked disease caused by a defective lysosomal enzyme,
      alpha-galactosidase A, and characterized by skin lesions and multiorgan
      involvement, including kidney, heart, and the central nervous system. Currently
      more than 200 genotypes have been identified, including several aberrant
      splicing. However, most of the mutation analyses were performed using genomic
      sequencing only, and therefore some of the splicing mutations were misclassified
      as missense mutations. In order to predict the splicing event caused by each
      mutation, we conducted a literature search for all published mutations located
      near the splice sites, including exonic point mutations, and performed a splice
      site score (SSS) analysis. The literature search identified 13 donor-site
      mutations, including four exonic mutations (S65T, D183S, K213N, and M267I),
      located at the end of exons 1, 3, 4, and 5, respectively, six acceptor-site
      mutations, and one new exon creation. All mutated splice sites, except for the
      one associated with the new exon creation, had a lower SSS than their respective
      natural sites. Cryptic or newly created sites were identified with SSS from 0.09
      to 1.0. The predictions, based on SSS analysis, are in agreement with all six
      mutations with known cDNA sequence from the literature, including five mutations
      with exon skipping and one mutation with creation of a new acceptor site. For the
      S65T genotype, we performed reverse transcription-polymerase chain reaction (RT
      PCR) analysis using RNA isolated from the whole-blood sample. We verified that a
      weak cryptic site (SSS = 0.09) 14 nucleotides downstream was activated and
      resulted in an insertion of 14 bp and a frameshift stop at codon 106. This change
      is more consistent with the clinical presentation of the patient, the classical
      Fabry disease, than the amino acid substitution (S65T), which does not affect the
      enzyme function. In conclusion, the SSS analysis is very useful for predicting
      splicing events and genotype/phenotype correlation in Fabry disease. As different
      mechanisms may be involved in pre-mRNA splicing, it is important to obtain cDNA
      sequencing for molecular diagnosis.

PMID- 12786755
TI  - Intact fetal cell isolation from maternal blood: improved isolation using a
      simple whole blood progenitor cell enrichment approach (RosetteSep).
AB  - Isolation and analysis of intact fetal cells in maternal blood is an attractive
      method of non-invasive prenatal diagnosis; however, detection levels are not
      optimal. The poor sensitivity and inconsistent recovery of fetal cells is
      compounded by small numbers of circulating fetal cells and loss of fetal cells
      during enrichment procedures. Optimizing selection criteria by utilizing less
      complicated methods for target cell enrichment is essential. We report here
      salutary results using a simple density-based depletion method that requires
      neither MACS (magnetic-activated cell sorting) nor flow cytometric separation for
      enrichment of progenitor cells. Maternal blood samples (n = 81) were obtained
      from women prior to invasive prenatal genetic diagnostic procedures and processed
      randomly within 24 h using one of two density-based enrichment methods. For
      progenitor cell enrichment, samples (n = 49) were labeled with a RosetteSep
      progenitor antibody cocktail to remove unwanted mature T-cells, B-cells,
      granulocytes, natural killer cells, neutrophils and myelomonocytic cells. For
      CD45-negative cell enrichment, samples (n = 14) were labeled with RosetteSep CD45
      antibody to remove unwanted maternal white cells. The desired cellular fraction
      was collected and analyzed by either fluorescent in situ hybridization (FISH) or
      real-time PCR for the presence of intact fetal cells and to quantify Y-chromosome
      specific DYS1 sequences, respectively. Overall, FISH and real-time PCR correct
      detection rates for the progenitor cell enrichment approach were 53% and 89% with
      3% (1 out of 30 cases) and 0% false-positive detection, respectively. Fetal
      sequences were detected in the range from 0.067 to 1.167 genome equivalents per
      milliliter of blood. No fetal cells were detected using the CD45-negative
      enrichment method. Flow cytometric analysis of cord blood showed that a unique
      myeloid population of cells was recovered using RosetteSep trade mark progenitor
      enrichment compared with the CD45-negative enrichment method. Sensitivity of the
      RosetteSep progenitor enrichment approach for detection of fetal cells in this
      pilot study shows great promise with recovery of cells that are suitable for FISH
      and automated microscope scanning. This simple and rapid method may also allow
      expansion in culture and characterization of the fetal cell type(s) that
      circulate in maternal blood, hence, greatly improving reliability of non-invasive
      prenatal diagnosis.

PMID- 12786756
TI  - Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe:
      France, Italy, Portugal and Spain.
AB  - Alpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious
      hereditary disorders in the world because it affects all major racial subgroups
      worldwide and there are at least 120.5 million carriers and deficient subjects
      worldwide. This genetic disease is related to a high risk for development of
      jaundice in infants, liver disease in children and adults, and pulmonary
      emphysema in adults. Moreover, AAT-deficiency carrier phenotypes (PiMS and PiMZ)
      and deficiency-allele phenotypes (PiSS, PiSZ, and PiZZ) are suspected to make
      subjects susceptible to a variety of other adverse health effects. As there is a
      limited database on the number of individuals affected by this disease worldwide,
      the authors of the present report collected data on control cohorts in genetic
      epidemiological studies published in the peer-reviewed literature worldwide. The
      data collected were used to estimate the numbers of carriers and deficiency
      allele combinations for the two most common defective alleles, namely PiS and
      PiZ, in over 58 countries worldwide. The present report focuses on the
      distribution of the PiS and PiZ deficiency alleles in France, Italy, Portugal,
      and Spain. The total number of individuals at risk for adverse health effects
      were as follows: 9, 101, 739 in France; 4, 289, 566 in Italy; 2, 659, 241 in
      Portugal; and 8, 903, 773 in Spain. The geographical distribution of individual
      control cohorts and estimates of the numbers of carriers and deficiency-allele
      phenotypes in each of these four southern European countries are shown in
      individual tables and maps. This report will be followed by other reports on the
      remaining countries in Europe, as well as worldwide.

PMID- 12786757
TI  - Neurological presentation of Ehlers-Danlos syndrome type IV in a family with
      parental mosaicism.
AB  - Ehlers-Danlos syndrome type IV (EDS-IV) is an autosomal-dominant disorder caused
      by a defect of type III collagen which leads to ruptures of arteries and hollow
      organs. Neurological presentation with muscle involvement and flexion
      contractures of the finger joints is uncommon. We clinically characterized seven
      members of a family with EDS-IV. The index patient, a young woman with an
      acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon
      retraction, finger flexion contractures and seizures. The mother had similar
      features and had experienced an ischemic stroke. Biochemical study in cultured
      fibroblasts and molecular analysis of the COL3A1 gene led to the diagnosis of EDS
      IV. A glycine substitution, p.G883V, within the triple helix of the alpha 1(III)
      chain, was found in the index patient and in the mother. The maternal grandfather
      and an aunt each had an abdominal aortic aneurysm, the rupture of which was the
      cause of death in the latter, at 40 years of age. Surprisingly, we found the
      mutation, as a mosaic, in the asymptomatic maternal grandmother. This expands the
      clinical spectrum of EDS type IV and confirms that in some families mosaicism can
      be identified as the source of the mutation.

PMID- 12786758
TI  - A novel dominant missense mutation--D179N--in the GJB2 gene (Connexin 26)
      associated with non-syndromic hearing loss.
AB  - Mutations of the GJB2 gene, encoding Connexin 26, are the most common cause of
      hereditary congenital hearing loss in many countries, and account for up to 50%
      of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few
      GJB2 mutations have been reported to cause an autosomal-dominant form of non
      syndromic deafness. We report on a family from southern Italy in whom dominant,
      non-syndromic, post-lingual hearing loss is associated with a novel missense
      mutation in the GJB2 gene. Direct sequencing of the gene showed a heterozygous G-
      >A transition at nucleotide 535, resulting in an aspartic acid to asparagine
      amino acid substitution at codon 179 (D179N). This mutation occurred in the
      second extracellular domain (EC2), which would seem to be very important for
      connexon-connexon interaction.

PMID- 12786759
TI  - A novel syndrome of combined immunodeficiency, autoimmunity and
      spondylometaphyseal dysplasia.
AB  - We describe here four patients who appear to have similar clinical and
      immunological features which constitute a novel syndrome. The patients present
      with short stature owing to spondylometaphyseal dysplasia and with severe
      infections as the result of a combined humoral and cellular immune deficiency.
      Presumably because of dysregulation of the immune system, all patients also
      developed autoimmune manifestations.

PMID- 12786760
TI  - Mapping a gene for 46,XY gonadal dysgenesis by linkage analysis.
AB  - 46,XY gonadal dysgenesis was transmitted as an autosomal-dominant trait in a
      large family with multiple affected members. Expressivity of the trait was highly
      variable, ranging from pure to partial gonadal dysgenesis associated with normal
      female genitalia or sexual ambiguity, to mild hypospadias in otherwise normal
      males. The phenotypic features of this trait appeared to be confined to the
      genitourinary system. Multipoint parametric analysis using markers D5S664,
      D5S633, and D5D2102 yielded an LOD score of 4.47, assuming sex-limited, autosomal
      dominant inheritance with a penetrance of 0.6. Because mutation in testis
      determining genes leads to gonadal dysgenesis in 46,XY individuals, we postulate
      that the gene mapped by this study normally plays a role in gonadal
      differentiation.

PMID- 12786761
TI  - Endoglin gene mutations and polymorphisms in Italian patients with hereditary
      haemorrhagic telangiectasia.
AB  - Autosomal-dominant hereditary haemorrhagic telangiectasia (HHT) is a genetically
      heterogeneous disease caused by mutations in at least two different loci. We
      screened for mutations in four Italian families where segregation studies showed
      clear evidence of linkage to the endoglin (ENG) locus. In addition, one sporadic
      case and three patients with pulmonary arteriovenous malformations, belonging to
      small nuclear families unsuitable for linkage analysis, were included in the
      screening. The proband from each family was investigated using single-strand
      conformation polymorphism and heteroduplex analysis; potential variants were
      sequenced. Four novel and one previously reported mutation were detected, as well
      as three new polymorphisms. The novel mutations included deletions in exon 1
      (patient 581/02), exon 5 (patient 780/01) and exon 7 (patient 700/01), and a C-
      >T229 substitution in exon 3 (patient 462/02). When analysing patient 700/01 and
      his affected daughter, we encountered a mutant ENG allele with two mutations--a
      deletion in exon 7 and a substitution in exon 12--which converts isoleucine 575
      into threonine, in a non-conserved region. Both mutations were absent in the two
      healthy sons of the patient, while the polymorphic variant in exon 12 was present
      in his healthy father. These results and haplotype-segregation studies suggest
      that a de novo deletion had occurred in the gamete of paternal origin. For the
      first time the parental germline in which a de novo HHT mutation occurred has
      been identified.

PMID- 12786762
TI  - Low prevalence of the deafness-associated 35delG mutation in the connexin-26
      (GJB2) gene in a Sicilian population.

PMID- 12786764
TI  - Giant cell arteritis: managing the ophthalmic medical emergency.

PMID- 12786765
TI  - Endophthalmitis after contemporary cataract surgery: defining incidence and risk
      factors.

PMID- 12786766
TI  - Oral and intravenous steroids in giant cell arteritis.
AB  - Giant cell arteritis can result in devastating visual loss. Treatment with
      steroids does result in visual recovery in some patients but the exact percentage
      is unknown. Intravenous megadose steroids appear to offer some advantage over
      oral steroids presumably through non-genomic effects, which manifest at doses of
      500 mg or more. Side-effects are more likely in the elderly especially those with
      renal and cardiac co-morbidities. The authors' current recommendation is that
      intravenous steroids should be given to patients with established visual loss or
      amaurosis fugax.

PMID- 12786767
TI  - Blink-related microtrauma: when the ocular surface harms itself.
AB  - Superior limbic keratoconjunctivitis results mechanically from blinking under
      prolonged unphysiological conditions. The pathogenic process is known as blink
      related microtrauma. This review aimed to explore the validity of a general
      theory that besides superior limbic keratoconjunctivitis, there may be other
      diseases of the ocular surface arising from mechanical microtrauma. A review of
      relevant clinical and microscopic lesions in a range of ocular surface disorders
      with possible mechanical aetiology was conducted. New terms were selected to
      facilitate understanding of such new aetiology. Besides superior limbic
      keratoconjunctivitis, other ocular surface disorders regarded as primarily
      derived from blink microtrauma are: other filamentary keratitides; blepharospasm
      and severe ptosis; canthal/palpebral froth; affections from disordered eyelid
      lining; and contact lens related damage. A group of secondarily microtraumatic
      disorders was identified, including the example of microtrauma impacting upon
      interpalpebral bulbar prominences. Superior limbic keratoconjunctivitis is the
      archetype of diseases affecting a unique combination; namely, the ocular surface
      conjoined with its lacrimal fluid. It is only one among many diseases actively
      generated within the confines of 'a self-harming surface'.

PMID- 12786768
TI  - Mitomycin C eliminates the short-term intraocular pressure rise found following
      Molteno tube implantation.
AB  - PURPOSE: Molteno implants remain popular for treating recalcitrant glaucomas.
      This study aimed to assess the effect of mitomycin C (MMC) use with Molteno tube
      implantation upon intraocular pressure (IOP) control and complication rates. In
      particular, the study aimed to assess any change that MMC might have upon the
      postoperative hypertensive phase. METHODS: A retrospective case record study was
      conducted of all patients undergoing double plate Molteno implant surgery by one
      surgeon over 5 years. Eyes with recalcitrant glaucoma unresponsive to previous
      surgery, or deemed unlikely to succeed with trabeculectomy, underwent double
      plate Molteno tube implantation. Eyes that had MMC (0.3 mg/mL, 3 min) applied to
      Tenon's capsule over the secondary plate were compared with eyes that underwent
      surgery without adjunctive MMC application. RESULTS: Twenty-seven eyes received
      MMC and were similar to 26 eyes not receiving MMC in terms of glaucoma subtype,
      age, sex, previous surgery, preoperative IOP and postoperative IOP lowering
      agents. Those not receiving MMC had raised IOP 31-90 days post implantation
      compared with MMC treated eyes (P < 0.01) and more often received oral
      antifibrosis medication (P < 0.05). Complications were no more common with MMC
      except for initial overdrainage. Significant systemic complications from the use
      of oral antifibrosis medication were common. CONCLUSIONS: The findings suggest a
      useful role for MMC. Caution is advised in case selection for MMC use. Mitomycin
      C treatment over the secondary plate alone permits removal of this plate if MMC
      related complications occur without requiring removal of the whole implant.

PMID- 12786769
TI  - Postoperative 5-fluorouracil versus intraoperative mitomycin C in high-risk
      glaucoma filtering surgery: extended follow up.
AB  - PURPOSE: To compare the long-term efficacy and safety of postoperative
      subconjunctival 5-fluorouracil (5-FU) injections with that of intraoperative
      mitomycin C (MMC) in eyes at high risk for failure of trabeculectomy. METHODS: In
      a retrospective, non-randomized comparative trial, 36 eyes of 36 consecutive
      patients at high risk for failure of trabeculectomy underwent glaucoma filtering
      surgery with either postoperative subconjunctival 5-FU injections (19 eyes) or
      intraoperative application of MMC (17 eyes). Intraocular pressure, number of
      postoperative antiglaucoma medications, postoperative visual acuity,
      interventions, and complications were evaluated. RESULTS: Overall success
      (intraocular pressure </=21 mmHg) at 1 year was 73.6% in the 5-FU group and 82.3%
      in the MMC group. The cumulative 4-year success was 52.6% in the 5-FU group and
      60.5% in the MMC group (P = 0.6). At 4-year follow up, mean +/- SD intraocular
      pressures were 17.58 +/- 4.01 mmHg in the 5-FU group and 13.33 +/- 3.36 mmHg in
      the MMC group (P = 0.01). There was no significant difference in the number of
      post-operative medications (P = 0.84), appearance of blebs (P = 0.20), final
      visual acuity (P = 1.00), and complications (P > 0.05) between the groups.
      CONCLUSIONS: These results suggest that both postoperative 5-FU injections and
      intraoperative MMC application have long-term success in high-risk patients.
      However, MMC results in a greater decrease in intraocular pressure than 5-FU.

PMID- 12786770
TI  - Supplementation of fexofenadine therapy with nedocromil sodium 2% ophthalmic
      solution to treat ocular symptoms of seasonal allergic conjunctivitis.
AB  - PURPOSE: Ocular symptoms are often under-treated in patients with allergic
      rhinoconjunctivitis. The efficacy of fexofenadine hydrochloride 60 mg capsules
      supplemented with nedocromil sodium 2% ophthalmic solution was evaluated to
      determine the optimal drug regimen for control of ocular allergic symptoms.
      METHODS: In this 5-week, open-label, randomized, multicentre comparative study,
      89 patients with documented ragweed pollen allergy received fexofenadine b.i.d.
      with nedocromil rescue, fexofenadine q.d. with nedocromil b.i.d., or fexofenadine
      rescue with nedocromil b.i.d. during the ragweed pollen season. RESULTS: For all
      regimens, mean symptom severity scores for itching, burning, tearing, redness,
      grittiness, discharge, light sensitivity and swelling improved significantly (P <
      0.003). Similarly, all groups experienced significant (P < 0.02) improvement in
      all clinical signs: erythema, oedema, discharge, conjunctival injection and
      conjunctivitis, as well as quality-of-life scores (P < 0.0001). All regimens
      reduced overall symptom severity scores after 5 min (P < 0.05) with relief
      persisting over 12 h (P < 0.03). Improvements in mean symptoms, signs and quality
      of-life scores were similar among the treatment groups as were onset and duration
      of action even though patients in two of the three study arms were taking one
      half or less of the recommended fexofenadine dosage. Patients and physicians
      judged the regimens containing lower fexofenadine dosages (with nedocromil
      b.i.d.) to be more effective overall than the regimen containing the highest fexo
      fenadine dosage (with nedocromil as rescue only). CONCLUSIONS: Supplementation of
      oral fexofenadine therapy with nedocromil sodium 2% ophthalmic solution relieves
      ocular symptoms of seasonal allergic rhinoconjunctivitis, allowing control of
      rhinal symptoms with half the recommended dosage of fexofenadine.

PMID- 12786771
TI  - Trends in cataract surgery and postoperative endophthalmitis in Western Australia
      (1980-1998): the Endophthalmitis Population Study of Western Australia.
AB  - OBJECTIVES: Postoperative endophthalmitis results from an intraocular infection
      and usually occurs following cataract surgery. It has significant morbidity and
      causes severe visual impairment or blindness of the eye. The aim of this study
      was to assess the trends in the incidence rates of cataract surgery and
      postoperative endophthalmitis in Western Australia for the period 1980-1998.
      METHODS: The Western Australian Record Linkage Project was used to link the
      morbidity records for all patients treated for cataract surgery in Western
      Australia in 1980-1998. Patient records were selected using the international
      classification for diagnosis and procedure codes pertaining to cataract surgery
      and postoperative endophthalmitis. All cases of postoperative endophthalmitis
      were validated by case-note review. The separate databases of the Royal Perth
      Hospital microbiology and anaesthetic departments as well as the vitreo-retinal
      surgeon logbooks were used to cross-validate the hospital morbidity database.
      Trends in the incidence rates of cataract surgery and postoperative
      endophthalmitis were assessed by Poisson regression. RESULTS: There were 94,653
      cataract procedures performed for 63,007 patients in Western Australia during the
      19-year period. The majority (88%) of cataract procedures performed were in
      patients aged 60 years or older. Postoperative endophthalmitis developed in 188
      patients, with serious visual impairment occurring in 70.6% of patients for whom
      visual acuity data was available at presentation. The incidence rate of cataract
      surgery increased more than three-fold from 1981 (102 per 100,000 person years)
      to 1998 (345 per 100,000 person years), mainly due to the increase in
      extracapsular cataract extraction during the 1980s and phacoemulsification
      extraction from 1990 onwards. In contrast, the average annual incidence rate of
      postoperative endophthalmitis remained relatively unchanged at around 2 per 1000
      cataract procedures over the same period. CONCLUSION: Cataract surgery is
      becoming more prevalent in the elderly as the life expectancy of the population
      increases. There has been a dramatic shift in surgical practice during the last
      30 years with small-incision phacoemulsification being the predominant method of
      intervention used since 1990. Despite changes in surgical practice the incidence
      rate of postoperative endophthalmitis has remained the same.

PMID- 12786772
TI  - Craniopharyngioma: a review of long-term visual outcome.
AB  - PURPOSE: To assess the clinical presentation and long-term visual outcome in a
      series of patients with craniopharyn-gioma. METHODS: Retrospective case review.
      RESULTS: Thirty-six patients were reviewed, comprising 19 female patients and 17
      male patients. The age range was 2-77 years with a bimodal distribution of 17
      children (mean age 10 years) and 19 adults (mean age 47 years). Blurred vision
      was the most common visual complaint (23 cases, 64%) and headache the most
      frequent systemic complaint (19 cases, 53%). The average duration of systemic
      symptoms was 45 weeks compared to 10 weeks for visual symptoms. Deficits in
      visual acuity occurred in 13 patients (36%) and showed no significant change from
      initial presentation to final review. Sixteen patients (44%) had bitemporal
      hemianopia on presentation and pleomorphism (change from one type of visual field
      defect to another) occurred in 11 patients. Recurrence of tumour occurred in 15
      patients (42%) and was more likely in children (59%) than adults (26%). The mean
      time period to recurrence was 7 years. The average follow-up period for all cases
      was 10 years. CONCLUSION: Patients with craniopharyngioma generally present late,
      and the visual symptoms are often preceded by a long history of systemic
      symptoms. Children are more likely to present with systemic symptoms than adults.
      Visual field pleomorphism is a feature of craniopharyngioma and occurred in one
      third of the patients. Local recurrence is common. Although magnetic resonance
      imaging is the recommended means of follow up, regular neuro-ophthalmic review is
      useful in the early detection of anterior visual pathway compression by recurrent
      tumour.

PMID- 12786773
TI  - Prevalence and associations of dry eye syndrome in an older population: the Blue
      Mountains Eye Study.
AB  - This report describes the prevalence of self-reported dry eye syndrome and
      associations with systemic and ocular factors in an older Australian population.
      Participants of the Extension Blue Mountains Eye Study, aged 50 or older (mean
      age 60.8 years, n = 1174) completed a comprehensive eye examination and dry eye
      questionnaire. At least one dry eye symptom was reported by 57.5% of
      participants, with 16.6% reporting moderate to severe symptoms, more frequent in
      women (age-adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.2).
      Three or more symptoms were reported by 15.3% of participants, also more frequent
      in women (age-adjusted OR 1.7, CI 1.2-2.4). No age-related trends or significant
      ocular associations were observed. After adjusting for age and sex, systemic
      factors significantly associated with dry eye syndrome included history of
      arthritis, asthma, gout, use of corticosteroids, antidepressants and hormone
      replacement therapy. In this older population, dry eye syndrome was common and
      has associations with female gender and systemic diseases.

PMID- 12786774
TI  - Projected prevalence of age-related cataract and cataract surgery in Australia
      for the years 2001 and 2021: pooled data from two population-based surveys.
AB  - This study aimed to estimate the number of Australians over 50 with cataract in
      the years 2001 and 2021. Data from two population-based studies were pooled: the
      Blue Mountains Eye Study and Melbourne Visual Impairment Project and Australian
      Bureau of Statistics population projections were used. Similar definitions for
      the three cataract types were used in the two studies (nuclear >/= grade 4,
      posterior sub-capsular >/= 1 mm, cortical >/= 10% lens area or >/= 25%
      circumference). Combining the three types and prior surgery, it was estimated
      that in 2001, 1.7 million Australians had clinically significant cataract in
      either eye and 320,000 had previously undergone cataract surgery. It was
      estimated that the number of persons with cataract will rise to 2.7 million by
      2021 (over 500,000 will have had cataract surgery). The number of Australians
      with cataract will grow by two-thirds during the next 20 years, reflecting
      continued population ageing. Health care delivery systems will need to develop
      methods to handle this increased workload.

PMID- 12786775
TI  - Prevalence of undetected ocular conditions in a pilot sample of school children.
AB  - Parents of 134 children (age 5-18 years; 84% participation) attending a private
      school gave informed consent for their child's participation in a pilot study to
      demonstrate the feasibility and estimate sample size for a larger study of myopia
      prevalence, the Sydney Myopia Study. LogMAR visual acuity and other ocular
      assessments, including cycloplegic autorefraction (tropicamide 1%) and
      examination of the media and fundus, were performed. The prevalence of
      significant ocular conditions was 28.2%. Eleven children (8.4%) wore glasses.
      Five were referred for a change in their correction. Previously undetected ocular
      conditions (19.8%) included one child with ocular pathology and four children
      with strabismus. Uncorrected refractive error (16.8%) was the most common reason
      for referral and was more predominant in the senior students (25%), corresponding
      with an age-related shift in mean spherical equivalent refraction towards myopia
      (less than 7 years: +0.40 +/- 0.60 D; more than 15 years: -1.15 +/- 1.18 D).
      Three senior students were classified as having socially significant correctable
      vision impairment. These findings suggest that reliance on ad hoc referrals could
      result in delayed referral and that vision screening in both early and later
      school years may be desirable.

PMID- 12786776
TI  - General purpose control system for scanning laser ophthalmoscopes.
AB  - A flexible control system for scanning laser ophthalmoscopes is described that is
      quick and simple to configure, easily modified or adapted, and containing many
      useful features. The system facilitates adjustment of several parameters to
      account for changes to the scan position, ambient light and temperature,
      including both optical and electronic components, which is otherwise difficult
      and time-consuming to perform. The system is portable and uses custom-designed
      printed circuit boards. All system parameters, such as focus, scan rate,scan
      depth and stereo control can be digitally controlled from a computer via a single
      serial port. Custom software allows changes to any system parameters by simply
      sending the required control data to the rack. The circuit boards in the system
      are multilayer,incorporating good ground-plane techniques to minimize noise,
      programmable logic and semicustom logic for low cost and compact size, and
      microcontrollers with embedded firm ware for flexible operation. Retinal images
      demonstrate that the system performs well.

PMID- 12786777
TI  - Muller cells express the neuronal progenitor cell marker nestin in both
      differentiated and undifferentiated human foetal retina.
AB  - Tritiated thymidine studies suggest that Muller cells are the last cells born in
      the retina, although several authors describe Muller cells throughout the retina
      from very early ages. In this study immunohistochemistry was used to identify
      progenitor and Muller cells in human foetal retina. Antibodies to nestin (an
      intermediate filament protein expressed by neural progenitor cells), vimentin,
      cellular retinaldehyde binding protein (CRALBP) and glutamate and aspartate
      transporter (GLAST), which are each expressed by Muller cells, were used in
      combination with anti-Ki67 to identify proliferating cells. By definition, Ki67
      positive proliferating cells were present in undifferentiated retina, but not in
      differentiated retina. Nestin-immunoreactive (IR) cells colocalized with vimentin
      throughout the retina. CRALBP-IR was detected in differentiated retina and in
      some proliferating cells. GLAST-IR cells were present only within the
      differentiated region. Nestin, vimentin and CRALBP each colocalized with mitotic
      Ki67-IR cells, suggesting that in foetal retina Muller cells and retinal
      progenitor cells are overlapping populations and that Muller cells are end-stage
      progenitor cells.

PMID- 12786778
TI  - Chronic placental insufficiency and foetal growth restriction lead to long-term
      effects on postnatal retinal structure.
AB  - The aim of this study was to determine the effects of foetal growth restriction
      on the retina after birth. Foetal growth restriction (FGR) was induced via
      umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until
      term (term approximately 147 days); controls were not exposed to UPE. Lambs were
      delivered and raised until 2 years of age when retinas were collected and
      processed for structural and neurochemical analysis. The foetuses exposed to UPE
      were hypoxemic and at birth were growth restricted. In 2-year-old FGR sheep, the
      total thickness of the retina and the number of tyrosine hydroxylase
      immunoreactive dopaminergic amacrine cells were reduced compared to controls (P <
      0.05). It is concluded that restricted foetal growth leads to long-term
      structural and neurochemical changes in the retina. Of particular interest are
      the alterations to dopaminergic amacrine cell numbers, as alterations in this
      population may affect contrast sensitivity and have implications for the
      alterations in vision observed in very low birthweight infants.

PMID- 12786779
TI  - Is there an auditory-visual flash-lag effect?
AB  - A flash adjacent to the path of a moving object appears behind the moving object:
      the 'flash-lag effect'. We sought to test the flash-lag effect with a 'click'
      instead of a flash: a white triangle horizontally traversed the screen at a
      constant 12 degrees /s passing through a fixation cross in the presence of a
      quiet click. The subject judged whether the click occurred before or after the
      triangle passed through the cross. To be perceived as co-instantaneous events,
      the click had to be presented 127 ms after the moving triangle reached the cross
      (a 'click-lead' effect, providing falsification of predictive accounts of the
      flash-lag effect), as opposed to a standard flash-lag effect condition where a
      flashed triangle replaced the click and had to appear 60 ms before the moving
      triangle to appear aligned. With the auditory versus visual processing speed
      advantage considered, the neural time required to calculate a moving object's
      position is constant, independent of the modality of the flag.

PMID- 12786780
TI  - Sensitivity to the acceleration of looming stimuli.
AB  - The aim of this study was to determine if observers could discriminate between
      looming stimuli simulating targets approaching the observers at either constant
      or non-constant speeds. Discrimination between accelerating and constant-speed
      approaches improved after 70-90 trials for accelerations >2 m/s2. For lower
      accelerations the ability to discriminate was poor regardless of the trial
      number. Following the learning phase, observers were able to identify
      accelerating targets from constant-speed approaches fairly consistently at
      performance levels of 70-75% for accelerations as low as 4 m/s2 and at 80-96% for
      accelerations of 6-14 m/s2. Observers' accuracy in identifying decelerating from
      constant-speed targets did not increase as a function of increasing deceleration.
      In fact, observers had a slight bias to select the constant-speed stimulus as
      being the decelerating stimulus. In summary, the sensitivity to acceleration for
      simulated motion in depth is poor, but increases as acceleration increases and
      sensitivity to acceleration is far greater than for deceleration.

PMID- 12786781
TI  - Light rise of the human electroretinogram is normal in retinitis pigmentosa.
AB  - AIM: To determine if the electroretinogram (ERG) light rise is reduced below
      normal in patients with retinitis pigmentosa (RP) and whether it is greater in
      patients with smaller ERG. METHODS: Both eyes of 31 normal subjects and 59
      subjects with RP had photopic ERGs on ISCEV standard and brighter backgrounds,
      before and after dark adaptation. Recordings <2.5 micro V were excluded. RESULTS:
      Ratios of amplitudes before and after dark adaptation varied little. The b-wave
      averaged 1.88 (SD 0.41) in normal subjects and 1.66 (SD 0.62) in RP subjects, and
      a-waves averaged 1.44 (SD 0.42) and 1.31 (SD 0.73), respectively. None of eight t
      tests were significant (<2.4). There was a positive (not negative) correlation
      between RP subjects' initial b-wave amplitude and light rise but not for a-waves.
      A-wave light rises were smaller. CONCLUSION: Retinitis pigmentosa does not reduce
      the light rise of recordable ERG. The light rise of the ERG is larger in those RP
      subjects with larger initial b-waves. This confirms previous findings. The
      difference between a- and b-waves in RP suggests post-receptoral processes are
      involved.

PMID- 12786782
TI  - Globe perforation following peribulbar injection.

PMID- 12786783
TI  - Fibrin tissue-filler glue for persistent epithelial defects.

PMID- 12786784
TI  - Acute retinal necrosis associated with painful orbitopathy.

PMID- 12786785
TI  - Peeling the internal limiting membrane in serous macular detachment associated
      with congenital optic disc pit.

PMID- 12786786
TI  - Mucoepidermoid carcinoma of the conjunctiva managed by frozen section-guided
      excision and lamellar keratoplasty.

PMID- 12786787
TI  - Evaluation of PMMA intraocular lenses marketed in India: editor's comment.

PMID- 12786788
TI  - Fluorinated ocular/periocular corticosteroids have caused death as well as
      glaucoma in children.

PMID- 12786789
TI  - Evaluation of PMMA intraocular lenses marketed in India: former editor's comment.

PMID- 12786790
TI  - Complications of bone marrow biopsy.

PMID- 12786791
TI  - Complications of trephine biopsy.

PMID- 12786792
TI  - Determination of minimal residual disease in leukaemia patients.

PMID- 12786793
TI  - The trouble with consent.

PMID- 12786794
TI  - Viral antigen-specific CD8+ T-cell responses are impaired in multiple myeloma.
AB  - Multiple myeloma (MM) is associated with defects of humoral and cellular
      immunity, however, little is known about the frequency and function of antigen
      specific CD8+ T cells. Such information might be critical for the development of
      immunotherapy for MM patients. As a model, we assessed the frequency and
      proliferation of CD8+ T cells specific for HLA-A*0201-restricted immunodominant
      epitopes from influenza A (Inf A) and Epstein-Barr virus (EBV). Experiments in
      identical twins demonstrated reduced numbers of antigen-specific T cells after ex
      vivo antigenic challenge in the MM twin when compared with the healthy twin.
      Similarly, the proliferation and frequency of EBV- and Inf A-specific T cells was
      also significantly reduced in a cohort of 24 previously untreated or
      conventionally treated MM patients when compared with 19 healthy individuals. In
      contrast, MM patients studied after receiving an autologous stem cell
      transplantation showed strikingly higher frequencies of EBV-specific T cells with
      potential to proliferate ex vivo, suggesting that EBV-specific T cells are
      readily expandable under these circumstances. These data identify an impaired
      response of CD8+ T cells in MM patients, which might in part explain the
      relatively limited success of anti-MM immunisations. Prospective studies will
      determine whether such immune assessment strategies may identify patients more
      likely to benefit from cancer immunotherapy.

PMID- 12786795
TI  - Protein kinase C-delta is commonly expressed in multiple myeloma cells and its
      downregulation by rottlerin causes apoptosis.
AB  - The growth and proliferation of multiple myeloma (MM) cells are influenced by
      various cytokines produced by bone marrow stromal cells. As cytokine interaction
      between malignant plasma cells and neighbouring stromal cells is important in the
      pathogenesis of MM, the understanding of intracellular signalling events elicited
      by this interaction is of central importance. Recent reports have shown that
      protein kinase C (PKC) is directly involved in modulating apoptosis in different
      cells types, including those of haematopoietic neoplasms. In the present study,
      we analysed the expression patterns of PKC isoforms in the myeloma cell lines
      U266, RPMI-8226 and K620. This analysis demonstrated common expression of PKC
      delta, PKC-iota, PKC- micro and PKC-zeta in all three myeloma cell lines. PKC
      delta expression in plasma cells from 11 patients with MM was also shown by
      immunohistochemistry, utilizing a monoclonal mouse anti-human PKC-delta antibody.
      U266 cells treated with the broad PKC inhibitor safingol (l-threo
      dihydrosphingosine) or the PKC-delta-specific inhibitor rottlerin (3'-[(8
      Cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'
      trihydroxy-5'-methylacetophenone) showed decreased PKC-delta in the particulate
      fraction and resulted in significant apoptosis. Primary myeloma cells also showed
      apoptosis after treatment with the PKC inhibitors, as detected by both flow
      cytometric and morphological evaluation. Our results indicate that PKC-delta is
      commonly expressed in myeloma cells and plays an important role in plasma cell
      survival.

PMID- 12786796
TI  - T-large granular lymphocyte lymphoproliferative disorder: expression of CD26 as a
      marker of clinically aggressive disease and characterization of marrow
      inhibition.
AB  - T-large granular lymphocyte lymphoproliferative disorder (T-LGL LPD) is an
      indolent disease characterized by prolonged cytopenia and the presence of
      circulating large granular lymphocytes in the patient's peripheral blood.
      Although the disease is commonly thought of as indolent, most patients eventually
      require therapy because of recurrent infections secondary to neutropenia as well
      as a need for frequent blood product transfusions. CD26 is a 110-kDa surface
      glycoprotein with an essential role in T-cell function, including being a marker
      of T-cell activation and a mediator of T-cell activating signals. In this study,
      we evaluated CD26 expression in T-LGL patients and correlate CD26 expression with
      clinical behaviour. In addition, we examined the potential mechanism of cytopenia
      that is associated with this disorder. Our findings suggest that CD26 is a marker
      of aggressive T-LGL LPD and that CD26-related signalling may be aberrant in T-LGL
      LPD. Furthermore, inhibition of granulocyte-macrophage colony-forming units may
      be mediated by CD8+ cells of T-LGL LPD patients and is major histocompatibility
      complex class I-restricted.

PMID- 12786797
TI  - A genome scan of 18 families with chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) accounts for about 30% of all leukaemias and
      is most prevalent in older individuals. Significant familial aggregation has been
      demonstrated but the mode of inheritance is unknown. Recurrent cytogenetic
      abnormalities are frequently found in CLL tumour cells but no susceptibility
      genes have been confirmed. We have collected clinical data and biospecimens on
      families ascertained for having at least two living patients with CLL. The
      current study included DNA samples from 94 individuals (38 affected patients) in
      18 families. We have carried out a genome scan using the ABI 28-panel medium
      density linkage mapping set (average spacing of 10 cM and average heterozygosity
      of 80%). Genotypes for 359 markers were scored. Multipoint limit of detection
      (lod) scores were calculated, assuming both dominant and recessive inheritance
      and allowing for increased penetrance with age and genetic heterogeneity. Non
      parametric linkage scores were also calculated. Lod scores of 1.0 or greater were
      found on regions of chromosomes 1, 3, 6, 12, 13 and 17, but none of these loci
      achieved statistical significance. Four of these six regions (6q, 13q, 12 and
      17p) coincide with areas where cytogenetic abnormalities are frequently observed
      in CLL tumour cells and are, therefore, strong candidate regions for containing
      germ line changes.

PMID- 12786798
TI  - Decreased treatment failure in recipients of HLA-identical bone marrow or
      peripheral blood stem cell transplants with high CD34 cell doses.
AB  - We studied the association between CD34 cell dose and transplant outcomes in 359
      bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients
      from human leucocyte antigen (HLA)-identical siblings, reported to the
      International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia
      were performed between 1995 and 1998. Patients were divided into those receiving
      below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg)
      grafts respectively. Cox proportional hazards regression was used to adjust for
      baseline patient-, disease- and transplant-related characteristics. Analysis of
      the BM recipients showed that high CD34 cell dose was associated with lower
      transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment
      failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC
      recipients, high CD34 dose was associated with faster recovery of neutrophils to
      > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P
      = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR
      = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment
      failure in recipients of HLA-identical sibling BM and PBSC transplants.

PMID- 12786799
TI  - Risks of mortality in children admitted to the paediatric intensive care unit
      after haematopoietic stem cell transplantation.
AB  - The risk of mortality in children admitted to the paediatric intensive care unit
      (PICU) after haematopoietic stem cell transplantation is felt to be very high.
      Life-threatening complications leading to PICU admission are due to organ
      toxicity caused by conditioning regimes and graft-versus-host disease (GVHD),
      systemic infections and other organ dysfunctions. Data collected between October
      1998 and December 2001 of paediatric patients undergoing haematopoietic stem cell
      transplantation and thereafter admitted to the PICU were retrospectively analysed
      in order to reveal the possible causes and risk factors related to death while in
      the PICU. Twenty-six PICU admissions were recorded. We found a mortality rate of
      57.7% and a 6-month survival rate of 23.1%. Univariate analysis identified an
      oncological paediatric risk of mortality (O-PRISM) score above 10 points,
      sustained renal failure and a failed negative fluid balance as significant
      predictors to non-survival.

PMID- 12786800
TI  - Flow cytometry detection of serotonin content and release in resting and
      activated platelets.
AB  - Early detection of platelet activation is important for the diagnosis and follow
      up of several pathological conditions that primarily or secondarily involve
      platelets in their pathogenesis. The golden standard assay to detect thrombocyte
      activation is represented by the release of serotonin, classically performed by
      demanding methodologies, such as high-performance liquid chromatography, 14C
      labelling and enzyme-linked immunosorbent assay (ELISA). We developed a non
      radioactive method, based on individual cells, for the detection of serotonin
      content in activated and resting platelets by flow cytometry. The assay was
      standardized on cells activated by Ca2+ ionophore or by sera from patients with
      heparin-induced thrombocytopenia (HIT). Cells were identified by CD41a surface
      staining and their serotonin content measured by specific antiserotonin
      intracytoplasmic staining, while their activation was independently shown by
      annexin V binding. Cellular degranulation was detected by flow cytometry in all
      the cases that were also positive by standard ELISA. Moreover, multiparametric
      flow cytometry analysis revealed that, although virtually all activated cells
      bind annexin V, serotonin was released only by the platelet subset that
      downmodulates surface CD41a.

PMID- 12786801
TI  - Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and
      plasminogen activator inhibitors 1 and 2 during normal pregnancy.
AB  - The use of von Willebrand factor [VWF antigen (WF:Ag)] measurement as a marker of
      endothelial cell activation for monitoring hypertensive pregnancies is limited by
      the poor definition of reference values. We reassessed these reference values
      using different assays, and those of the propeptide (VWF:Ag II) and factor VIII
      coagulant activity (factor VIII:C), in a large population of normal pregnancies,
      at 3-week intervals of gestational age. Plasminogen activator inhibitors (PAI-1
      and PAI-2) were measured in parallel. Blood was collected at single time points
      between 12 weeks and delivery in 306 women undergoing normal singleton pregnancy.
      For clinical purposes, the VWF:Ag reference values were assay independent and the
      influence of ABO blood group on VWF:Ag or factor VIII:c was found to be limited
      during the third trimester. VWF:Ag II was not influenced by the ABO blood group.
      The ratio, VWF:Ag/factor VIII:C was close to 1.0 throughout pregnancy. In
      contrast, VWF:Ag II increased more slowly than VWF:Ag and the ratio of VWF:Ag II
      to VWF:Ag in plasma decreased from 1.00 to 0.5 at term. PAI-1 and PAI-2 increased
      with gestational age, but PAI-2 decreased during the last 2 weeks, indicating
      physiological placental regression at the very end of pregnancy.

PMID- 12786802
TI  - Intracellular localization of glycoprotein VI in human platelets and its surface
      expression upon activation.
AB  - Glycoprotein (GP) VI is a major receptor for collagen and belongs to the
      immunoglobulin super family. Here, we examined the localization of GPVI in
      resting and activated human platelets by immunogold scanning and transmission
      electron microscopy and flow cytometry. Ultrastructural observation detected
      immunolabelling for GPVI that was distributed uniformly over the entire surface
      of resting platelets, and revealed that GPVI was also localized on both the
      membranes of the surface-connected open canalicular system (OCS) and alpha
      granules. The OCS- and alpha-granule-associated GPVI pools were an estimated 35.4
      +/- 3.2% (mean +/- standard deviation) of the total. Little GPVI labelling was
      observed in any part of GPVI-deficient platelets. A remarkable time-dependent
      increase in GPVI surface expression was found by flow cytometry when platelets
      were activated by collagen-related peptide (CRP) and convulxin. The GPVI-mediated
      activation of platelets by CRP or convulxin resulted in similar ultrastructural
      changes and an increased GPVI labelling density on the activated platelet
      surface, which was accompanied by a decreased interior expression. GPVI was also
      expressed on microparticles generated from activated platelets. Thus, our study
      demonstrates that platelets have internal pools of GPVI, and that GPVI is
      increasingly redistributed to the surface membrane and to microparticles during
      platelet activation.

PMID- 12786803
TI  - Delayed-onset neutropenia associated with rituximab therapy.
AB  - The characteristics of severe neutropenia with a delayed onset following
      administration of rituximab have been evaluated in 53 consecutively treated
      patients. All but one patient received rituximab for the treatment of non
      Hodgkin's lymphoma. Eight episodes of grade 4 neutropenia were detected between 1
      and 5 months after rituximab, when administered alone on five occasions, and on
      three occasions in combination with chemotherapy, where neutrophil counts had
      recovered prior to the development of neutropenia. In three episodes, the
      patients presented with sepsis. Development of neutropenia did not correlate with
      either the presence of detectable disease or the administration of further
      treatment. Neutropenia was associated with selective depletion of neutrophil
      precursors in all but one episode, where it was associated with generalized bone
      marrow hypoplasia. All episodes developed after a period of either normal or
      mildly depressed neutrophil counts following treatment with rituximab, and
      persisted for between several days and several months, before undergoing
      spontaneous recovery in four instances, and after administration of filgrastim in
      the remainder. Episodes of neutropenia were associated with disordered immune
      status manifested by lymphopenia and hypogammaglobulinaemia, raising the
      possibility that either disturbance of the balance of lymphocyte subsets or an
      immune dyscrasia induced by rituximab resulted in the development of this type of
      neutropenia.

PMID- 12786804
TI  - Reduction of cell cycle progression in human erythroid progenitor cells treated
      with tumour necrosis factor alpha occurs with reduced CDK6 and is partially
      reversed by CDK6 transduction.
AB  - Tumor necrosis factor alpha (TNFalpha) potently inhibits the in vitro growth of
      highly purified human d-6 erythroid colony forming cells (ECFC). Unlike the
      inhibitory effect of TNFalpha on other cells, including more immature ECFC, this
      antiproliferative effect of TNFalpha is not related to apoptosis because the d-6
      cell descendants were morphologically normal, without apoptosis by terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling assay and
      without caspase activation by Western blots after TNFalpha treatment. TNFalpha
      did not appear to affect the cell cycle distribution, but the cell cycle duration
      was significantly longer in TNFalpha-treated cells. DNA synthesis was also
      significantly reduced by TNFalpha. Studies of various proteins that regulate the
      cell cycle showed that cyclin-dependent kinase 6 (CDK6) protein and mRNA levels
      were concomitantly decreased in the presence of TNFalpha, suggesting that
      inhibition of cell growth was related to reduced CDK6. To evaluate this, the CDK6
      gene was transferred into ECFC using green fluorescence protein-retrovirus
      mediated gene transfer. The results showed that the level of cell growth produced
      by TNFalpha was increased by 30% when the cells were transfected with CDK6.
      Therefore, the modification of cell cycle progression in the presence of TNFalpha
      through a reduction of CDK6 is an important mechanism in the TNFalpha inhibition
      of human ECFC expansion.

PMID- 12786805
TI  - Dissociation of ABH antigen expression from von Willebrand factor synthesis in
      endothelial cell lines.
AB  - ABO blood group determines plasma von Willebrand factor (VWF) levels and ABH
      antigens are present on VWF. To investigate whether ABO influences the rate of
      VWF synthesis, we performed stable transfection of A transferase in a
      phenotypically group-O endothelial cell line (EAhy926). A transferase expression
      did not affect the rate of VWF synthesis. Although high levels of A antigen were
      expressed on the cell surface, no A determinants were added to VWF synthesized
      within these cells. Further studies demonstrated H structures were not present on
      EAhy926-derived VWF, despite the fact that H antigen is constitutively expressed
      by these cells.

PMID- 12786806
TI  - Transcranial Doppler ultrasonography in siblings with sickle cell disease.
AB  - The risk of stroke in sickle cell disease (SCD) may be influenced by either
      genetic or environmental factors. Elevated blood flow velocity in the large
      cerebral arteries, detected by transcranial Doppler (TCD) ultrasonography,
      predicts an increased stroke risk in children with SCD. We undertook this study
      to investigate the possibility of a familial predisposition to elevated cerebral
      blood flow velocity, a surrogate marker for stroke risk. We analysed the results
      of TCD studies performed on 63 children from 29 families that had more than one
      child with SCD. We assessed the association of elevated cerebral blood flow
      velocity with sibling TCD results as well as age and haemoglobin level, which are
      factors known to affect cerebral blood flow velocity. Positive or negative TCD
      results were highly correlated between family members (r = 0.61). The presence of
      a sibling with a positive TCD result was significantly associated with an
      elevated cerebral blood flow velocity in other siblings with SCD (odds ratio =
      50.7, 95% confidence interval 10.1-253.7, P < 0.001). Furthermore, children who
      had a sibling with a positive TCD result had a significantly higher TCD velocity
      than children with SCD but without a sibling who were matched for age, sex,
      genotype and haemoglobin level. Our results are consistent with a familial
      predisposition to cerebral vasculopathy in SCD.

PMID- 12786807
TI  - Monitoring long-term efficacy of iron chelation therapy by deferiprone and
      desferrioxamine in patients with beta-thalassaemia major: application of SQUID
      biomagnetic liver susceptometry.
AB  - In this non-randomized prospective study, liver and spleen iron concentrations
      were monitored annually over a 4-year period by non-invasive Superconducting
      Quantum Interference Device biomagnetometry in 54 beta-thalassaemia major
      patients (age, 7-22 years) receiving treatment with deferiprone (75 mg/kg/d).
      Median liver iron concentrations increased significantly from 1456 to 2029 and
      2449 microg/g(liver) at baseline, after 2.0 and 3.2 years respectively. Another
      group of 51 thalassaemic patients (aged 4-34 years) who received desferrioxamine
      s.c. for 1.9 years increased their liver iron concentration from 1076 to 1260
      microg/g(liver). Taking into account the increase of the daily iron input from
      transfusions of 3.6 mg/d, caused by weight gain in 67% of the patients treated
      with deferiprone, a larger total body iron elimination rate was achieved after 2
      years than at baseline. A negative ferritin change was observed in 51% of the
      patients. In 15 non-splenectomized patients, liver iron significantly increased
      from 1260 to 1937 microg/g(liver) (P < 0.01), but serum ferritin remained stable
      at 2100 microg/l, as did the spleen iron concentration at 1200 microg/g(spleen).
      A two-compartment model may predict an average chelation efficacy for
      desferrioxamine and deferiprone, with a saturation effect of the latter, for a
      certain chelation and transfusion regimen by a single liver iron quantification.

PMID- 12786808
TI  - Bone marrow biopsy morbidity and mortality.
AB  - A postal survey of adverse events associated with bone marrow biopsy (aspiration
      biopsy with or without trephine biopsy) was carried out among British Society of
      Haematology members, between 1995 and 2001. A total of 26 adverse events,
      including one death directly attributable to the procedure, were reported among
      an estimated 54 890 biopsies. The most frequent and most serious adverse event
      was haemorrhage, reported in 14 patients, necessitating blood transfusion in six
      patients and leading to the single death. The potential risk factors most often
      associated with haemorrhage were a diagnosis of a myeloproliferative disorder,
      aspirin therapy or both. Other potential risk factors were warfarin therapy,
      disseminated intravascular coagulation and obesity.

PMID- 12786809
TI  - The use of "touchdown" polymerase chain reaction increases the sensitivity and
      specificity of t(11;14)(q13;q32) detection in patients with mantle cell lymphoma.

PMID- 12786810
TI  - Fluorescence in situ hybridization and conventional cytogenetics for the
      diagnosis of 11q23+/MLL+ translocation in leukaemia.

PMID- 12786811
TI  - Risk of parvovirus infection by immunoglobulin.

PMID- 12786815
TI  - Dirt, worms and atopic dermatitis.
AB  - The past three decades have witnessed a marked rise in the prevalence of atopic
      diseases in industrialized countries and urban centres in less developed regions.
      This has led to an intense search for aetiological factors that may explain such
      a pattern. Epidemiological and immunological data suggest the eradication of
      nonparasitic and endoparasitic infections as possible aetiological elements. This
      has been formulated as the 'hygiene hypothesis', linking a reduced frequency of
      childhood infections with allergy. So far, most work in this area has focused on
      asthma. The potential relationship between endoparasites and atopic dermatitis
      has received much less attention. This paper reviews the scientific literature on
      the links between atopic dermatitis and endoparasites. At present, there is no
      clear evidence for a direct relationship between the two. This may be due to the
      overall small number of studies and insufficient methodological rigour in the
      existing body of research.

PMID- 12786816
TI  - Updates from the Third International Congress on Psoriasis: From Gene to Clinic,
      The Royal College of Physicians, London, U.K., 21-23 November 2002.

PMID- 12786817
TI  - Expression of T-cell activation marker CD134 (OX40) in lymphomatoid papulosis.
AB  - BACKGROUND: CD134/OX40 and CD30 are transmembrane proteins from the tumour
      necrosis factor receptor (TNFR) family present selectively on activated T cells.
      TNFR-related proteins are crucially involved in the regulation of proliferation
      and survival of normal and malignant lymphohaematopoietic cells. CD30 has been
      used for the immunophenotyping and subclassification of cutaneous lymphomas;
      virtually nothing is known, however, about the expression pattern of CD134 in
      lymphoid skin malignancies. OBJECTIVES: To determine CD134 expression in
      cutaneous lymphoma and benign inflammatory disorders. METHODS: Biopsy material
      was obtained from patients with lymphomatoid papulosis (LyP, n = 42), mycosis
      fungoides (n = 21), Jessner's infiltrates (n = 10) and non-specific dermatitis (n
      = 14). The expression of CD134 and CD30 was scored after immunohistochemical
      staining with appropriate monoclonal antibodies. The proportion of G2 + S phase
      cells was determined by laser scanning cytometry from nuclei obtained from
      paraffin-embedded biopsies. RESULTS: Few, single and scattered CD134+ cells (<
      10%) were observed in the benign inflammatory infiltrations and in mycosis
      fungoides. A subset of 16 patients with LyP presented with clusters of CD30+
      CD134+ cells. There was no correlation between the magnitude of CD134 expression
      and the histological type or the proportion of G2 + S cells in LyP. CD134
      immunoreactivity was lower than expected in patients with LyP and another
      lymphoid malignancy (P < 0.001, Fisher's exact test). CONCLUSIONS: CD134 is
      strongly expressed in a proportion (38%) of patients with LyP, but not in mycosis
      fungoides or benign lymphocytic infiltrations. Loss of CD134 expression in LyP
      may be a marker of an increased risk of second lymphoid malignancy.

PMID- 12786818
TI  - Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma.
AB  - BACKGROUND: Mutations of the patched (Ptc) gene, a developmental regulator
      implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened
      (Smo), play an essential pathogenic role in the development of basal cell
      carcinomas (BCCs). We previously reported the upregulation of Shh signal
      transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In
      vertebrates, specific downstream effectors in the Shh signalling pathway include
      three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only
      an activation domain, while Gli2 and Gli3 contain both activation and repression
      domains. It remains unclear which of these transcription factors are responsible
      for the development of BCCs. OBJECTIVES: To examine the expression pattern of
      Gli2 mRNA by human BCCs in comparison with those by normal human skin and various
      skin tumours. METHODS: We performed quantitative reverse transcriptase-polymerase
      chain reaction analyses with a series of samples from BCCs, other skin tumours
      and normal skin. RESULTS: We found that Gli2 mRNA expression was enhanced in the
      BCCs we examined, whereas there was no significant increase in other skin tumours
      or normal skin. Of four spliced Gli2 isoforms designated Gli2alpha, beta, gamma
      and delta, the expression of Gli2beta mRNA was increased the most in BCCs.
      CONCLUSIONS: As Gli2beta is an isoform spliced at the first splicing site
      containing a repression domain and consists of an intact activation domain, its
      overexpression may lead to the upregulation of the Shh signalling pathway,
      thereby inducing BCCs.

PMID- 12786819
TI  - Differential expression of cornified cell envelope precursors in normal skin,
      intraorally transplanted skin and normal oral mucosa.
AB  - BACKGROUND: Skin flaps have routinely been used as substitutes for oral mucosa
      after extensive resection of oral tissues. However, it remains unknown how the
      transplanted skin flaps perform as a host defence in the new environment of the
      oral cavity. OBJECTIVES: To evaluate the expression of cornified cell envelope
      (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin
      and normal oral mucosa, because CCEs are highly responsible for a protective
      barrier in each type of epithelium. METHODS: We used immunohistochemistry and
      immunoelectron microscopy to examine the expression of CCE precursors, small
      proline-rich protein (SPR) 2 and 3 and loricrin, in biopsy specimens of normal
      skin, transplanted skin and normal oral mucosa, including buccal and lingual (non
      keratinized) mucosae, and palatal (keratinized) mucosa. RESULTS: Transplanted
      skin flaps were classified into two groups. About two-thirds of the transplanted
      skin flaps displayed a reddish appearance and were devoid of the stratum corneum
      (SC) together with a psoriasiform inflammatory tissue reaction. Others showed a
      native appearance, retaining the SC. While SPR2 expression was limited to the
      stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it
      extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and
      that of the normal oral mucosa. Although SPR3 expression was not found in normal
      skin or in the transplanted skin retaining the SC, it was strongly expressed in
      the SS of the transplanted skin lacking the SC and the non-keratinized oral
      mucosa, and in the SS and SG of the keratinized oral mucosa. Loricrin, which was
      expressed in the SG of normal skin, the transplanted skin retaining the SC and
      the keratinized oral mucosa, was not detected in the transplanted skin lacking
      the SC or in the non-keratinized oral mucosa. Immunoelectron microscopy confirmed
      the ultrastructural localization of SPR3 directly under the cytoplasmic membrane
      of keratinocytes of the transplanted skin lacking the SC and that of the oral
      mucosa. CONCLUSIONS: The altered expression of SPR2, SPR3 and loricrin reflects
      the possible adaptation of epidermal keratinocytes in the new environment of the
      oral cavity.

PMID- 12786820
TI  - Chemical peeling with salicylic acid in polyethylene glycol vehicle suppresses
      skin tumour development in hairless mice.
AB  - BACKGROUND: Chemical peeling with salicylic acid in polyethylene glycol (PEG)
      vehicle is used clinically to improve the cosmetic appearance of skin that has
      been damaged by exposure to the sun. It is well known that cancers of the skin
      such as basal cell carcinoma and squamous cell carcinoma may be induced by the
      sun. However, the carcinogenic potential of chemical peeling agents has not been
      studied. OBJECTIVES: To evaluate the effects of chemical peeling with 30%
      salicylic acid in PEG on skin tumour formation in treated vs. control mice.
      METHODS: To serve as a model of sun-damaged skin, hairless SKH/hr1 mice were
      irradiated with ultraviolet (UV) B for 14 weeks, with or without treatment every
      2 weeks with 30% salicylic acid in PEG for a total of 18 weeks. RESULTS: Not only
      was the total number of tumours greatly reduced in the treated vs. the control
      mice, but skin tumour development was also slower in the treated vs. the control
      mice. At the final treatment, the fractions of T and B lymphocytes and natural
      killer cells from spleens of both groups of mice were comparable, and interferon
      gamma production did not differ. CONCLUSIONS: Our findings suggest that chemical
      peeling with salicylic acid in PEG may help to prevent as well as to reduce the
      number of UVB-induced skin tumours.

PMID- 12786821
TI  - Oxidative stress in malignant melanoma and non-melanoma skin cancer.
AB  - BACKGROUND: Solar ultraviolet (UV) radiation is considered to be a major
      aetiological factor in melanoma and non-melanoma skin cancer. A growing body of
      evidence indicates that oxidative stress is involved in photocarcinogenesis.
      However, in vivo data for human skin are still lacking. Reactive oxygen species
      participate in a number of pathophysiological processes including DNA damage and
      lipid peroxidation (LPO) and are considered to be a key factor in tumour
      progression. OBJECTIVES: We hypothesized that in human skin cancer the natural
      redox balance is disturbed and that this imbalance may result in an accumulation
      of LPO products. METHODS: To test this, skin biopsies of superficial spreading
      melanoma were compared with age-matched benign melanocytic naevi and young
      healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma,
      squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each).
      Expression of the antioxidant enzymes, copper-zinc superoxide dismutase,
      manganese superoxide dismutase and catalase was analysed by immunohistochemical
      techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was
      visualized. RESULTS: In human melanoma biopsies, a significant overexpression of
      the antioxidant enzymes was found when compared with surrounding non-tumour
      tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO
      marker MDA was significantly increased in melanoma tissue. MDA was located not
      only in typical melanoma cells, but also occurred in surrounding keratinocytes.
      In contrast, a severely disturbed antioxidant balance with diminished antioxidant
      enzymes was found in non-melanoma tumours, whereas MDA was elevated only in
      squamous cell carcinomas. CONCLUSIONS: These findings indicate that oxidative
      stress may play different roles in the pathogenesis of human skin cancers. In non
      melanoma skin cancer, a diminished antioxidant defence caused by chronic UV
      exposure might contribute to multistep carcinogenesis, whereas melanoma cells
      exhibit increased oxidative stress which could damage surrounding tissue and thus
      support the progression of metastasis.

PMID- 12786822
TI  - Maggots and wound healing: an investigation of the effects of secretions from
      Lucilia sericata larvae upon interactions between human dermal fibroblasts and
      extracellular matrix components.
AB  - BACKGROUND: Through clinical observation, Lucilia sericata (greenbottle fly)
      larvae are credited with exerting the following beneficial effects upon a chronic
      nonhealing wound: removal of necrotic tissue ('debridement'), disinfection of the
      wound and active promotion of granulation tissue formation. As a major cellular
      component of granulation tissue, fibroblasts play an extensive role in healing.
      The composition of extracellular matrix (ECM) located in the wound is another
      important factor, partaking in a dynamic feedback loop with the fibroblasts that
      produce it. Fibroblast-ECM interactions therefore exert considerable influence
      upon new tissue formation. OBJECTIVES: To investigate the effects of L. sericata
      larval excretory/secretory products (ES) upon the behaviour of fibroblasts,
      seeded upon ECM component surfaces. METHODS: ES were collected by washing freshly
      hatched larvae in phosphate-buffered saline. Human dermal neonatal fibroblast
      cells were seeded upon fibronectin- or collagen-coated surfaces, together with
      untreated (or 'native') ES, heat-treated ES, or no ES (ES blank). Following
      incubation, fibroblast adhesion was determined using an adenosine triphosphate
      assay and, for confirmation, a total nucleic acid content assay. Cell spreading
      was observed using microscopy. The effect of ES upon fibronectin structure was
      observed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
      Peptide sequencing of suspected fibronectin fragments was performed using an
      'electrospray' type time of flight mass spectrometer and 'Peptident' database
      search. RESULTS: ES significantly reduced fibroblast adhesion to both fibronectin
      and, to a lesser extent, collagen. Cell spreading was also reduced, yet cells
      remained viable. For both spreading and adhesion, heat-treated ES exerted
      significantly less activity than native, untreated ES. However, they still
      exhibited significant activity when compared with the ES blank. ES appeared to
      modify fibroblast adhesion indirectly via proteolytic fragmentation of the
      fibronectin protein surface. CONCLUSIONS: L. sericata larval secretions modify
      fibroblast adhesion and spreading across ECM protein surfaces, while keeping
      cells viable. Proteolytic activity of the ES played a significant role. If
      transferred to the wound situation, such alteration of fibroblast-ECM
      interactions may enhance new tissue formation.

PMID- 12786823
TI  - Lichen sclerosus is frequently present in penile squamous cell carcinomas but is
      not always associated with oncogenic human papillomavirus.
AB  - BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing
      lesions of lichen sclerosus (LS). However, the prevalence of histological changes
      of LS in penile SCC is not well established. Moreover, mucosal oncogenic human
      papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been
      systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the
      prevalence of LS histological changes and of mucosal oncogenic HPV in a series of
      patients with penile SCC. METHODS: Consecutive cases of histologically proven
      penile SCC from a single university hospital over a 14-year period were
      retrospectively selected and reviewed. Histological signs of LS were
      systematically sought. HPV was detected by polymerase chain reaction (PCR)
      amplification of DNA from paraffin-embedded skin samples using general primers
      GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31-
      and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The
      mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18
      (44%) cases, SCC was associated with histological features of LS. Seventeen skin
      biopsy specimens of SCC (nine without and eight with LS histology) were subjected
      to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five
      of nine SCCs without histological features of LS were positive for mucosal HPV:
      three with HPV type 16 and two with only general primers. In contrast, all eight
      SCCs associated with LS were negative for oncogenic HPV types, although one was
      positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently
      associated with LS histological changes. As with vulval SCC, we found that non-LS
      associated penile SCC tended to be frequently associated with oncogenic HPV
      infection, whereas LS-associated penile SCC was not. Larger series are needed to
      confirm this association.

PMID- 12786824
TI  - Human placental amnion is a novel substrate for detecting autoantibodies in
      autoimmune bullous diseases by immunoblotting.
AB  - BACKGROUND: Identification of antigens by immunoblotting techniques, using
      epidermal and dermal extracts, is regarded as essential for making a definitive
      diagnosis in autoimmune bullous diseases (AIBDs). These procedures involve
      epidermal-dermal separation for subsequent protein extraction, which may result
      in partial loss of some antigenic polypeptides and changes in the conformational
      epitopes targeted by autoantibodies in AIBDs. It may therefore be necessary to
      use different substrates for consistent results. Objectives To evaluate the
      usefulness of human placental amnion extract as a substrate for immunoblotting in
      the diagnosis of AIBDs. METHODS: We checked the structural components of the
      desmosomes and basement membrane zone (BMZ) of amnion by electron microscopy.
      Using immunofluorescence and immunoblotting techniques, we tested the amnion
      immunoreactivity with antibodies to desmosomal and BMZ proteins, and with sera
      from 76 patients with AIBDs including pemphigus vulgaris, pemphigus foliaceus,
      bullous pemphigoid (BP), pemphigoid gestationis, linear IgA bullous dermatosis,
      epidermolysis bullosa acquisita, paraneoplastic pemphigus and mucous membrane
      pemphigoid. RESULTS: The desmosomes and BMZ of the amnion tissue were
      ultrastructurally similar to those in skin. Antigen mapping confirmed that amnion
      contains all the proteins that were recognized by a panel of monoclonal and
      polyclonal antibodies. Immunoblotting showed that the antibodies clearly detected
      bands corresponding to desmogleins 1 and 3, desmocollins 1 and 2, desmoplakins 1
      and 2, three subunits (alpha3, beta3 and gamma2) of laminin 5, BP antigens 1 and
      2, the 97-kDa LAD antigen and type VII collagen. In addition, most of the patient
      sera (82%) reacted exclusively with their respective antigens. CONCLUSIONS:
      Harvesting proteins from amnion does not require epidermal-dermal separation, and
      a sufficient yield of desmosomal and hemidesmosomal proteins can be obtained.
      Therefore, amnion may be a more reliable source of substrate than skin samples
      for immunoblot analysis of AIBDs.

PMID- 12786825
TI  - The cellular origins of the linear IgA disease target antigens: an indirect
      immunofluorescence study using cultured human keratinocytes and fibroblasts.
AB  - BACKGROUND: Linear IgA disease (LAD) is an IgA-mediated subepidermal
      immunobullous disease of adults and children, with heterogeneous immunopathology.
      Objectives To investigate to what extent the cellular origins of the target
      antigens account for the heterogeneity of the immune response in LAD. METHODS:
      Forty-nine adult and 33 childhood LAD sera were studied. Immunofluorescence was
      carried out to determine the expression of the LAD antigens by normal human
      keratinocytes, fibroblasts and mixed cultures of keratinocytes and fibroblasts.
      Immunoblotting was performed to determine the localization of the LAD target
      antigens in tissue extracts (48 adult and 31 childhood sera) and cell extracts
      (21 adult and 10 childhood sera). RESULTS: Thirty-one adult and 13 childhood LAD
      sera bound proteins expressed by human keratinocytes; of these sera, 15 adult and
      four childhood LAD sera also recognized proteins expressed by fibroblasts. A
      single adult serum was positive on fibroblasts alone. Seventeen adult and 20
      childhood sera were negative on both cell types. There was a modest increase (9%)
      in the detection of the IgA autoantibodies on keratinocytes and fibroblasts grown
      together in mixed culture. Immunoblotting showed that the LAD target antigens
      could be detected in cell as well as in tissue extracts. CONCLUSIONS: Our results
      have shown that normal human keratinocytes and fibroblasts in culture express the
      LAD target antigens. LAD sera (with a single exception) bound antigens expressed
      by keratinocytes alone or by both keratinocytes and fibroblasts. The principal
      pattern of expression in keratinocytes was cytoplasmic, similar to that
      demonstrated by polyclonal antibodies to the 180-kDa bullous pemphigoid antigen
      (BP180). This reflects the pivotal role of BP180 in LAD. The finding that LAD
      antigens are expressed by both human keratinocytes and fibroblasts in culture may
      explain the heterogeneity of the target antigens, and may be a contributory
      factor in the immunopathology of the disease.

PMID- 12786826
TI  - Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV
      immune response in patients with atopic dermatitis.
AB  - BACKGROUND: Microbiological infections are considered to be of pathophysiological
      importance in atopic dermatitis (AD). As yet, no information is available
      regarding cytomegalovirus (CMV) infection in this disease. This, however, is of
      interest because of the high prevalence of latent infections in the general
      population, the frequent reactivation in inflammatory diseases, and the
      immunomodulating capacity of CMV. OBJECTIVES: To investigate the prevalence of
      latent CMV infection, the frequency of active CMV infection, and the immune
      response to CMV in patients with moderate to severe AD. Methods To detect active
      infection we analysed CMV antigen expression by peripheral blood mononuclear
      cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53
      healthy volunteers. We used three monoclonal antibodies recognizing different CMV
      encoded antigens and immunocytological staining (alkaline phosphatase
      antialkaline phosphatase technique). RESULTS: Patients with AD had a higher mean
      frequency of CMV-positive PBMC: 2.25 per 10 000 vs. 0.74 per 10 000 in controls
      (P = 0.001) as well as a higher incidence of CMV antigenaemia: 29.6% vs. 7.5% (P
      < 0.01). Seropositivity for anti-CMV IgG antibodies indicated subclinical
      activation of latent infection. Remarkably, a clearance of CMV antigenaemia was
      observed during anti-eczematous treatment. Significantly higher plasma levels of
      tumour necrosis factor-alpha, which is involved in CMV reactivation, and
      interleukin-12, which is crucial for an antiviral cellular immune response, were
      observed in AD patients in comparison with healthy volunteers. Furthermore, a
      significantly enhanced frequency of circulating activated HLA-DR+ T cells
      especially in CMV-seropositive AD patients (19.3% vs. 13.5% in seronegative AD
      patients vs. 10.2% in controls) suggested that the active CMV infection triggers
      a cellular immune response. This was also supported by a high frequency of CMV
      specific interferon-gamma-producing T cells in CMV-seropositive patients with AD.
      CONCLUSIONS: Our data suggest that active, subclinical CMV infection is more
      frequent in patients with moderate to severe AD and may have
      immunopathophysiological relevance.

PMID- 12786827
TI  - Expression of beta-catenin in basal cell carcinoma.
AB  - Background beta-Catenin is a crucial member of the E-cadherin/catenin complex,
      which plays a major role in cell-cell adhesion. beta-Catenin is also known to be
      involved in signal transduction pathways. Many studies have demonstrated changes
      in the expression of beta-catenin in colorectal carcinomas, suggesting a role for
      beta-catenin in neoplastic development. Objectives Basal cell carcinoma (BCC) is
      a locally invasive tumour. The various subtypes show differences in biological
      behaviour. This study aimed to investigate the presence of differences in the
      immunoprofile of beta-catenin among histological variants of BCC. Methods Eighty
      BCCs were studied (32 nodular, 7 micronodular, 24 superficial and 17 infiltrative
      and morphoeic). Formalin-fixed, paraffin-embedded tissue sections were stained
      for beta-catenin using the avidin/biotin immunodetection technique. Results All
      the nodular BCCs showed membranous and weak cytoplasmic staining. Nuclear
      staining was seen in 15 of 32 (47%) cases, being stronger at the periphery of the
      nodules in 11 of 15 (73%) of these cases. In superficial BCCs the membranous
      staining was variable and cytoplasmic staining was increased. Nuclear staining
      was seen in 16 of 24 (67%) cases, being more notable at the periphery in 8 of 16
      (50%) of these cases. All micronodular BCCs showed strong membranous staining,
      weak cytoplasmic and no nuclear staining. In the infiltrative and morphoeic BCCs
      membranous staining was completely lost at the advancing margins of the invading
      cell strands, with a marked increase in cytoplasmic staining; nuclear staining
      was observed in all these tumours. Conclusions The expression of beta-catenin
      varied between different types of BCC. Nuclear localization was most notable in
      the infiltrative and morphoeic variants, followed by the superficial variant, and
      seen least in nodular BCC. Its prominence at tumour margins suggests that this
      may be associated with more aggressive types of invasion.

PMID- 12786828
TI  - Reduced expression of actin-binding proteins, h-caldesmon and calponin h1, in the
      vascular smooth muscle inside melanoma lesions: an adverse prognostic factor for
      malignant melanoma.
AB  - BACKGROUND: The structural integrity of the blood vessels such as small arteries
      and veins is studied less frequently in malignant tumours than is angiogenesis.
      Objectives To clarify the characteristics of small arteries and small veins of
      melanoma lesions. METHODS: We immunohistochemically investigated various types of
      melanocytic tumours using antibodies specific for endothelial and vascular smooth
      muscle cells, and analysed the relationship between the expression of these
      molecules in the blood vessels and the biological characteristics of the tumours.
      Formalin-fixed, paraffin-embedded sections of 15 cases of benign melanocytic
      tumours and 64 cases of malignant melanomas were investigated. RESULTS:
      Significant suppression of expression of h-caldesmon (h-CD) and calponin h1
      (CNh1) was observed in the blood vessels of malignant melanomas compared with
      both benign melanocytic tumours and normal tissues. In particular, the level of h
      CD expression was inversely correlated with the frequency of metastasis and
      positively correlated with the survival rate in patients with malignant melanoma.
      CONCLUSIONS: These findings suggest that alterations of the tumour vessels are an
      important factor for the prognosis of malignant melanoma, and that suppression of
      h-CD and CNh1 in the blood vessels in malignant melanoma reflects a structural
      fragility of the vessels, leading to their easy penetration by tumour cells.
      Defective expression of these molecules is likely to be an important marker for
      metastatic potential and for poor prognosis of melanoma.

PMID- 12786829
TI  - Pattern analysis, not simplified algorithms, is the most reliable method for
      teaching dermoscopy for melanoma diagnosis to residents in dermatology.
AB  - BACKGROUND: Simplified algorithms for dermoscopy in melanoma diagnosis were
      developed in order to facilitate the use of this technique by non-experts.
      However, little is known about their reliability compared with classic pattern
      analysis when taught to untrained observers. OBJECTIVES: To investigate the
      diagnostic performance of three different methods, i.e. classic pattern analysis
      and two of the most used algorithms (the ABCD rule of dermoscopy and the seven
      point check-list) when used by newly trained residents in dermatology to diagnose
      melanocytic lesions. Methods Five residents in dermatology (University of
      Florence Medical School) were submitted to a teaching programme in dermoscopy
      based on both formal lessons and training and self-assessment using a newly
      developed, interactive CD-ROM on dermoscopy. The performance of the three
      diagnostic methods was analysed in a series of 200 clinically equivocal
      melanocytic lesions including 44 early melanomas (median thickness 0.30 mm; 25th
      75th percentile 0.00-0.58 mm). RESULTS: Pattern analysis yielded the best mean
      diagnostic accuracy (68.7%), followed by the ABCD rule (56.1%) and the seven
      point check-list (53.4%, P = 0.06). The best sensitivity was associated with the
      use of the seven-point check-list (91.9%), which, however, provided the worst
      specificity (35.2%) of the methods tested. The interobserver reproducibility, as
      shown by kappa statistics, was low for all the methods (range 0.27-0.33) and did
      not show any statistical difference among them. CONCLUSIONS: Pattern analysis,
      i.e. simultaneous assessment of the diagnostic value of all dermoscopy features
      shown by the lesion, proved to be the most reliable procedure for melanoma
      diagnosis to be taught to residents in dermatology.

PMID- 12786830
TI  - Scalp ringworm in south-east London and an analysis of a cohort of patients from
      a paediatric dermatology department.
AB  - BACKGROUND: Scalp ringworm or tinea capitis has become an increasingly important
      public health issue in the past decade in Great Britain. Recently, certain
      dermatology departments in London have seen a large increase in tinea capitis in
      all its forms. OBJECTIVES: The aim of this paper is to present the detailed
      analysis of a cohort of 277 patients with tinea capitis seen during a 2-year
      period together with the latest local figures of tinea capitis cases from an
      inner city paediatric dermatology service. Methods Demographic, clinical and
      laboratory data were collected prospectively over 2 years from all cases of
      ringworm in patients seen in a paediatric clinic specially set up for scalp
      problems. RESULTS: Sixty-two per cent of 277 cases of scalp ringworm were caused
      by Trichophyton tonsurans, occurring mainly (91%) in patients with Afro-Caribbean
      hair type, more often in boys (68%), and in the 3-8 year olds (70%). Only 7% of
      the patients had received appropriate treatment with oral griseofulvin. An
      additional 156 cases from the general paediatric dermatology clinic showed 91%T.
      tonsurans infections. CONCLUSIONS: The prevalence of scalp ringworm appears to be
      reaching epidemic proportions in certain areas that include south-east London.
      The clinical problem is not yet well recognized by local general practitioners.

PMID- 12786831
TI  - The impact of skin diseases on patients: comparing dermatologists' opinions with
      research data collected on their patients.
AB  - BACKGROUND: Research data suggest that the detection of psychiatric disorders by
      dermatologists is not completely satisfactory, and that patients and
      dermatologists often assess patients' quality of life differently. Given that
      expectations influence perception and cognitia, these discrepancies might at
      least in part descend from conceptual models of skin disease that are prevalent
      among dermatologists. OBJECTIVES: We explored to what degree dermatologists'
      opinions about quality of life and prevalence of psychiatric disorders in several
      dermatological conditions corresponded to the actual data collected on their
      patients. METHODS: All dermatologists working in a large institution were asked
      to express on a five-point scale their opinion about the quality of life and the
      prevalence of depressive and anxiety disorders in different skin conditions.
      Physicians' opinions were then compared with the results of a large research
      project on quality of life and psychological well-being in dermatological out
      patients performed in their institution some months before. RESULTS: Forty-six
      dermatologists (82%) agreed to participate and completed the research
      questionnaire. We observed a fairly good concordance between dermatologists'
      opinion about the impact of the various skin conditions on patients' lives and
      survey data on quality of life impairment. With regard to psychiatric morbidity,
      we found that dermatologists believe that psychiatric disorders are substantially
      less frequent than they actually are in many skin conditions. CONCLUSIONS: The
      belief that psychiatric morbidity is rare in patients with certain skin
      conditions might hamper, at least in part, the recognition of psychiatric
      disorders in these patients. Dermatologists probably should be more alert to the
      question of psychiatric morbidity in their patients. Allocating more space to
      this issue in training programmes for dermatologists might favour a shift in
      their conceptual models of skin disease.

PMID- 12786832
TI  - The effects of ultraviolet B treatment on the expression of adhesion molecules by
      circulating T lymphocytes in psoriasis.
AB  - BACKGROUND: T lymphocytes are believed to play a role in the pathogenesis of
      psoriasis; > 80% of T lymphocytes that infiltrate psoriatic lesions express the
      surface glycoprotein cutaneous lymphocyte-associated antigen (CLA), compared with
      < 20% in the blood. Exposure to ultraviolet (UV) B is an effective treatment for
      psoriasis. OBJECTIVES: To compare the effects of UVB treatment of psoriasis on
      the expression of CLA and several other surface markers expressed by circulating
      T lymphocytes. METHODS: Peripheral blood mononuclear cells from psoriatic
      patients were stained for adhesion molecules and stimulated with streptococcal
      antigens before and once weekly during 3 weeks of UVB treatment. RESULTS: A
      marked and progressive decrease was observed during the treatment in expression
      of the CLA and the very late antigen-4alpha by T cells; this decrease correlated
      closely with clinical improvement (Psoriasis Area and Severity Index). T-cell
      expression of intercellular adhesion molecule-1 was not significantly affected
      during the treatment and no change was observed in the activation markers CD25
      and CD69 or lymphocyte proliferation after stimulation with streptococcal
      antigens or superantigens. CONCLUSIONS: UVB treatment is associated with a marked
      reduction in the expression of skin-homing molecules by circulating T cells. This
      may be relevant to the therapeutic effect of UVB in psoriasis.

PMID- 12786833
TI  - Effects of selenium compounds on induction of DNA damage by broadband ultraviolet
      radiation in human keratinocytes.
AB  - Background Ultraviolet radiation (UVR), a ubiquitous environmental genotoxin for
      the skin, produces DNA damage. The trace element selenium induces synthesis of
      the glutathione peroxidase and thioredoxin reductase enzyme families. These
      selenoenzymes detoxify a range of toxic compounds generated by free radicals.
      Objectives To assess the effects of pretreatment of primary human keratinocytes
      with selenium on UVR-induced DNA damage. Methods Cells were irradiated with UVR
      from FS-20 lamps and were subjected to comet assay. Results Comet tail length due
      to UVR-induced T4 endonuclease V-sensitive sites (caused by cyclopyrimidine
      dimers, CPDs) increased to 35 +/- 4.5 microm (mean +/- SD) immediately after
      irradiation (time 0 h, 100%). After 4 h, 68% of the damage remained and after 24
      h, 23% of the damage was still present. Treatment with up to 200 nmol L-1
      selenomethionine or 50 nmol L-1 sodium selenite had no effect on CPD formation or
      rates of repair, or on the number of excision repair sites as measured by
      cytosine arabino furanoside and hydroxyurea treatment. However, selenite and
      selenomethionine protected against oxidative damage to DNA as measured by
      formation of formamidopyrimidine (FaPy) glycosylase-sensitive sites, which are
      indicative of 8-hydroxy-2-deoxyguanosine photoproduct formation. In this assay,
      irradiation of keratinocytes increased mean +/- SD glycosylase-specific comet
      tail length from 5 +/- 1.5 microm to 19 +/- 3.3 microm. Preincubation for 18 h
      with 50 nmol L-1 selenite abolished the UVR-induced increase in comet length.
      Preincubation with 200 nmol L-1 selenomethionine was similarly protective.
      Conclusions Selenite and selenomethionine protect keratinocytes from UVR-induced
      oxidative damage, but not from formation of UVR-induced excision repair sites.

PMID- 12786834
TI  - Short-term effects of topical fusidic acid or mupirocin on the prevalence of
      fusidic acid resistant (FusR) Staphylococcus aureus in atopic eczema.
AB  - BACKGROUND: Staphylococcus aureus has a role in the pathophysiology of atopic
      eczema. Topical fusidic acid is widely used in its treatment. There is concern
      that topical use of fusidic acid may be driving the selection and dissemination
      of fusidic acid-resistant (FusR) S. aureus. OBJECTIVES: To test the hypothesis
      that treatment of atopic eczema for 2 weeks with topical fusidic acid/steroid
      combination can increase carriage of FusRS. aureus. METHODS: Forty-six patients
      with atopic eczema were allocated randomly to one of two treatment groups. Group
      1 (28 patients) were treated with topical 2% fusidic acid plus 0.1% betamethasone
      cream, and group 2 (18 patients) with topical 2% mupirocin and 0.1% betamethasone
      cream. The clinical response and nasal and skin colonization with S. aureus were
      recorded before treatment and after 1 and 2 weeks of therapy. RESULTS: Baseline
      samples from the site of worst eczema showed S. aureus (sensitive and resistant)
      in 76% of patients, and FusRS. aureus in 26%, with no significant difference
      between treatment groups. After 1 and 2 weeks, both groups showed similar
      significant clinical improvement. The overall median clinical improvement was
      paralleled by a reduction in prevalence and population density of S. aureus
      (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for
      FusRS. aureus there was no significant change in the prevalence of carriage, or
      population density in either group compared to baseline. Over 50% of patients
      carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither
      regimen affected either the prevalence or population density of S. aureus or
      FusRS. aureus in the nerves. CONCLUSIONS: In this small study there is no
      evidence to support the hypothesis that short-term treatment of atopic eczema
      with fusidic acid/steroid combination increases fusidic acid resistant S. aureus
      during a 2-week period.

PMID- 12786835
TI  - High levels of fusidic acid-resistant Staphylococcus aureus in dermatology
      patients.
AB  - BACKGROUND: Antibiotic resistance is a significant problem both in hospitals and
      the community. Topical antibiotics are widely used for dermatological problems
      and this may be leading to the emergence of resistant bacteria. OBJECTIVE: To
      assess the level of fusidic acid-resistant Staphylococcus aureus inpatients with
      dermatological problems. METHODS: All microbiology samples over a 4-month period
      were tested for antibiotic sensitivities. Patients with cultures positive for S.
      aureus were studied. RESULTS: The study shows 50% of S. aureus isolates from
      dermatology patients were resistant to fusidic acid. This figure rose to 78%
      inpatients with atopic eczema. Of patients with fusidic acid-resistant S. aureus
      isolates, 96% had used a fusidic acid-containing preparation within the previous
      6 months. The level of fusidic acid resistance in S. aureus samples cultured from
      nondermatology patients was only 9.6%, a level significantly below that for
      dermatology patients (P < 0.001). CONCLUSIONS: High levels of fusidic acid
      resistant S. aureus are found in dermatology patients. Inappropriate use of
      topical antibiotics in dermatology patients leading to fusidic acid resistance
      may threaten the efficacy of systemic fusidic acid for the treatment of serious
      S. aureus infections. Education of health professionals and restriction of the
      use of fusidic acid is needed.

PMID- 12786836
TI  - Increased innervation of the vulval vestibule in patients with vulvodynia.
AB  - BACKGROUND: Vulval vestibulitis is a condition characterized by the sudden onset
      of a painful burning sensation, hyperalgesia, mechanical allodynia, and
      occasionally pruritus, localized to the region of the vulval vestibulus. It is
      considered the commonest subset of vulvodynia. Pain precipitated in the absence
      of nociceptor stimuli might be triggered by previous peripheral nerve injury, or
      by the release of neuronal mediators, which set off inappropriate impulses in
      nonmyelinated pain fibres sensitizing the dorsal horn neurones. The
      pathophysiology of vulval vestibulitis is still unclear. OBJECTIVES: The
      objective of this study was to evaluate the nerve fibre density and pattern, in
      specimens of vulval vestibulus, in normal subjects and in patients with
      vestibulitis, and provide objective diagnostic criteria for this condition.
      Methods Twelve patients with a history of the vestibulitis type of vulvodynia,
      and eight normal subjects underwent biopsy of the posterior wall of the vulval
      vestibule. Quantitative immunohistochemistry was performed, using antisera to the
      general neuronal marker protein gene product (PGP) 9.5, and to the neuropeptide
      calcitonin gene-related peptide (CGRP), on 15- microm sections. RESULTS: There
      was a statistically significant increase of density and number of PGP 9.5
      immunoreactive in the papillary dermis of patients with vulvodynia of the
      vestibulitis type, compared with those of controls. However, the distribution
      pattern of the innervation showed no significant change. There were no
      significant differences in CGRP staining between patients and controls.
      CONCLUSIONS: It is concluded that the increase of PGP 9.5 immunoreactive nerve
      fibres, in patients with vulvodynia, may be either secondary to nerve sprouting,
      or may represent neural hyperplasia. Increased innervation may be applied as an
      objective diagnostic finding in vulval vestibulitis syndrome.

PMID- 12786837
TI  - Dermatofibrosarcoma protuberans with COL1A1 (exon 18) -PDGFB (exon 2) fusion
      transcript.
AB  - BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet
      derived growth factor B-chain (PDGFB) gene has been described in
      dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have
      been shown to be involved in the fusion with exon 2 of the PDGFB gene. Objectives
      We examined the breakpoint of the COL1A1 gene using the tumour specimen from the
      patient with DFSP. METHODS: Reverse transcriptase-polymerase chain reaction (PCR)
      was performed using cultured DFSP tumour cells. Nucleotide sequence analysis was
      carried out using the PCR product to identify the breakpoint. RESULTS: The COL1A1
      PDGFB fusion transcript was detected from the tumour specimen. Sequence analysis
      revealed that exon 18 of the COL1A1 gene was fused with exon 2 of the PDGFB gene.
      CONCLUSIONS: This study identified a novel COL1A1 breakpoint, namely, exon 18 of
      the COL1A1 gene.

PMID- 12786838
TI  - Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus
      infection.
AB  - Association of drug-induced hypersensitivity syndrome with viral infection is
      debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently
      reported infection associated with this syndrome. However, a case of
      cytomegalovirus (CMV) infection was recently described associated with
      anticonvulsant-induced hypersensitivity syndrome. We report a case of severe
      allopurinol-induced hypersensitivity syndrome with pancreatitis associated with
      Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two
      consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM
      antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV
      nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase
      chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6
      was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA
      was not detected by PCR in the serum. Other viral investigations showed previous
      infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination
      (hepatitis B virus), or absence of previous infection (hepatitis C virus, human
      immunodeficiency virus). We suggest that EBV infection may participate in some
      cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug
      induced hypersensitivity syndrome.

PMID- 12786839
TI  - Slow acetylator genotypes as a possible risk factor for infectious mononucleosis
      like syndrome induced by salazosulfapyridine.
AB  - We report two patients with infectious mononucleosis-like syndrome induced by
      salazosulfapyridine (SASP). In both cases, high fever, skin rash, liver
      dysfunction and atypical lymphocytosis developed 3 weeks after initiating
      treatment with SASP. SASP is known to be mainly metabolized by N
      acetyltransferase 2 (NAT2), and acetylation phenotypes (rapid, intermediate and
      slow acetylator) correlate with NAT2* genotypes. In our two patients, we
      investigated NAT2* genotypes by the polymerase chain reaction-restriction
      fragment length polymorphism method. We identified NAT2*6/*7 in one patient, and
      NAT2*6/*5 in the other, suggesting that both were slow acetylator phenotypes. In
      20 healthy volunteers we found no slow acetylator genotypes. Genotyping prior to
      medication may be useful in evaluating patients with a high risk of severe
      systemic reaction to SASP.

PMID- 12786840
TI  - Cowden's disease: clinical and molecular genetic findings in a patient with a
      novel PTEN germline mutation.
AB  - We report a 54-year-old woman with Cowden's disease (CD) who was found to carry a
      novel germline mutation in the PTEN gene. The mutation (c.334C-->G) introduced a
      splice donor site within exon 5 that caused the expression of an aberrant
      transcript lacking 159 nucleotides corresponding to codons 112-164. Clinically,
      the patient showed multiple benign hamartomatous lesions of the skin,
      papillomatosis of the lips and oral mucosa, polyposis coli and bilateral
      fibrocystic disease of the breast. In addition, she developed different types of
      malignant neoplasms, including bilateral carcinomas of the breast and malignant
      melanomas of the skin. Molecular genetic analysis of a benign skin hamartoma and
      an invasive ductal breast carcinoma revealed loss of heterozygosity (LOH) at
      microsatellite markers on chromosome 10 in the carcinoma but not in the
      hamartoma. The breast carcinoma additionally carried a somatic TP53 point
      mutation (c.466C-->G; R156G) that was associated with LOH on 17p and nuclear p53
      protein accumulation. Taken together, our findings indicate that benign
      hamartomas in CD may develop without loss of the second (wild-type) PTEN allele,
      whereas the pathogenesis of malignant tumours, such as breast carcinomas, appears
      to require the complete inactivation of Pten as well as further alterations such
      as the loss of p53-dependent growth control.

PMID- 12786841
TI  - Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens
      recessive dystrophic epidermolysis bullosa.
AB  - We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic
      epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell
      carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower
      than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92
      previously described patients with DEB to develop SCC. This study emphasizes the
      importance of vigilance in monitoring the possible development of SCC in DEB
      patients regardless of age or clinical severity.

PMID- 12786842
TI  - A case of childhood dermatofibrosarcoma protuberans without detected cytogenetic
      abnormality.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumour of
      intermediate malignancy, with a limited potential for metastasis but a high rate
      of recurrence; specific cytogenetic abnormalities are now known. Childhood DFSP
      has been considered a rarity in the past, but it is now recognized that many
      cases of childhood DFSP are diagnosed only in adulthood. Despite advances in the
      understanding of its pathogenesis as well as the development of valuable
      immunohistochemical and cytogenetic diagnostic techniques, there often remains a
      significant delay between the initial presentation and diagnosis of DFSP. We
      report a case of childhood DFSP in which the diagnosis was reached only after a
      nodular lesion developed in a plaque that was initially present. Causes for delay
      between initial presentation and diagnosis in childhood DFSP are discussed.
      Histology and immunostaining in our patient showed the typical features of DFSP,
      but the G-banded cytogenetic analysis of short-term tissue culture was negative.
      However, this technique offers only a detection rate between 50% and 80%.
      Clinicians should be aware of the limitations of newer diagnostic techniques.
      Increasing recognition amongst paediatricians and paediatric dermatologists that
      childhood DFSP is not as rare as once believed will probably lead to the use of
      newer diagnostic methods at an earlier stage, and so reduce the delay between the
      onset of symptoms and diagnosis.

PMID- 12786843
TI  - Subacute lupus erythematosus-like eruption due to terbinafine: report of three
      cases.

PMID- 12786844
TI  - Favus due to Trichophyton schoenleinii in a patient with metastatic bronchial
      carcinoma.

PMID- 12786845
TI  - A case of anti-p200 pemphigoid clinically mimicking inflammatory epidermolysis
      bullosa acquisita.

PMID- 12786846
TI  - Cutaneous Rosai-Dorfman disease: remission with thalidomide treatment.

PMID- 12786847
TI  - Classic Kaposi's sarcoma of the palm in a metallurgist: role of iron filings in
      its development?

PMID- 12786848
TI  - Agranulocytosis and total scalp alopecia following acitretin.

PMID- 12786849
TI  - Mucinous naevus with atypical features.

PMID- 12786850
TI  - Delayed presentation of persistent unilateral cutaneous mottling of the arm
      following coarctation of the aorta.

PMID- 12786851
TI  - Adult staphylococcal scalded skin syndrome: histological pitfalls and new
      diagnostic perspectives.

PMID- 12786852
TI  - Sarcomatoid carcinoma of the liver with skin and pleural metastases.

PMID- 12786853
TI  - Exudative hyponychial dermatitis associated with capecitabine and docetaxel
      combination chemotherapy for metastatic breast carcinoma: report of three cases.

PMID- 12786854
TI  - Acute pigmentation due to minocycline therapy in atopic dermatitis.

PMID- 12786855
TI  - Phakomatosis pigmentokeratotica associated with hypophosphataemic vitamin D
      resistant rickets: improvement in phosphate homeostasis after partial laser
      ablation.

PMID- 12786856
TI  - Azathioprine hypersensitivity in a patient with peripheral demyelinating
      polyneuropathy.

PMID- 12786857
TI  - Hold on the amputation.

PMID- 12786859
TI  - Cryoglobulinaemic vasculitis, cryofibrinogenaemia and low-grade B-cell lymphoma.

PMID- 12786860
TI  - BDS Melanoma Guidelines.

PMID- 12786862
TI  - Zinc sulphate for viral warts.

PMID- 12786863
TI  - Genital lichen sclerosus, squamous cell carcinoma and circumcision.

PMID- 12786865
TI  - A case of naevus lipomatosus cutaneus superficialis of the scalp associated with
      pedunculated basal cell carcinoma.

PMID- 12786866
TI  - Could ectoparasites act as vectors for prion diseases?
AB  - Prion diseases are rare neurodegenerative diseases of humans and animals with a
      lethal evolution. Several cell types found on the human skin, including
      keratinocytes, fibroblasts and lymphocytes, are susceptible to the abnormal
      infective isoform of the prion protein, which transforms the skin to produce a
      potential target for prion infection. Iatrogenic transmission of Creutzfeldt
      Jakob disease was also recognized after corneal transplants in humans, and
      scrapie was successfully transmitted to mice after ocular instillation of
      infected brain tissue, confirming that these new routes, as well as cerebral
      inoculation and oral ingestion, could be important in prion infections. Animal
      prion infections, such as scrapie (sheep) and "mad cow disease" (cattle), have
      shown a pattern of horizontal transmission in farm conditions and several
      ectoparasites have been shown to harbor prion rods in laboratory experiments. Fly
      larvae and mites were exposed to brain-infected material and were readily able to
      transmit scrapie to hamsters. New lines of evidence have confirmed that adult
      flies are also able to express prion proteins. Because ocular and cerebral
      myiases and mite infestation are not rare worldwide, and most cases are caused by
      fly larvae or hay mites that usually affect sheep and cattle, it is important to
      discuss the possibility that these ectoparasites could eventually act as
      reservoirs and/or vectors for prion diseases.

PMID- 12786867
TI  - Possible applications of videodermatoscopy beyond pigmented lesions.

PMID- 12786868
TI  - Alopecia areata: psychiatric comorbidity and adjustment to illness.
AB  - BACKGROUND: Decades ago, alopecia areata (AA) was regarded as a well-known
      example of psychosomatic disease. The poor development of measurement methods and
      criteria for the classification of psychiatric disorders at that time was
      probably partly to blame for the lack of methodologic validity of some studies.
      METHODS: We studied a random sample of 32 patients with AA (patchy form).
      Sociodemographic, dermatologic, and psychiatric variables were collected.
      Psychiatric examination was carried out by standardized interviews: Schedules for
      Clinical Assessment in Neuropsychiatry (SCAN), International Personality
      Disorders Examination (IPDE), and Psychological Adjustment to Illness Scale
      (PAIS), using the Research Diagnostic Criteria of the International
      Classification of Diseases, 10th edition, to assess the diagnosis. A descriptive
      and association study was performed, correlating the patient's adjustment and
      adaptation to the illness to various factors (linear regression techniques and
      analysis of variance). RESULTS: Sixty-six per cent of patients presented with
      psychiatric comorbidity, mainly adjustment disorders (F.43.2), generalized
      anxiety disorders (F.41.1), and depressive episodes (F.32). Overall adaptation to
      the illness, however, was satisfactory, showing few repercussions in family or
      social life, work, or sexual adjustment. Poor adjustment was associated with a
      dependent personality (Pearson's r = 0.66), antisocial personality (r = 0.39),
      generalized anxiety (P = 0.003), and depression (P = 0.02). CONCLUSIONS: There is
      a high psychiatric comorbidity in AA (anxiety and mood disorders), requiring
      systematic psychiatric evaluations of these patients. A satisfactory overall
      adaptation to mild/moderate forms of the disease is the norm, but adaptation and
      comorbidity in severe forms (totalis, universalis) are unknown. A
      dermatology/liaison psychiatry setting could improve the management of AA.

PMID- 12786869
TI  - Sweet's syndrome with neurologic manifestation: case report and literature
      review.
AB  - BACKGROUND: Sweet's syndrome with involvement of the central nervous system (CNS)
      is rarely reported. METHODS: We describe a Japanese woman with Sweet's syndrome
      associated with acute-onset encephalitis and review literatures. RESULTS:
      Examination of the cerebrospinal fluid (CSF) revealed pleocytosis with
      lymphocytes predominant. Magnetic resonance imaging (MRI) revealed increased
      signal intensity on T2-weighted scans in the left temporal lobe. To our
      knowledge, 22 cases of Sweet's syndrome associated with CNS involvement have been
      reported. The mean age is 47.6 years (n = 22). Sex distribution (male : female)
      is 12 : 10 (n = 22). The most common neurologic symptoms are convulsions,
      headaches, and disturbance of consciousness. CSF cell count is increased with
      lymphocytes predominant in 8 cases (n = 12). Certain (HLA) types (B54 and Cw1)
      may be characteristic findings in Sweet's syndrome accompanied with the CNS
      involvement in Japanese patients, as these were found in four previous cases
      similar to the present case. CONCLUSIONS: Although Sweet's syndrome with
      neurologic manifestations is rarely reported, it may be needed to investigate
      neurologic manifestations.

PMID- 12786870
TI  - Measuring the severity of rosacea: a review.
AB  - BACKGROUND: Assessment of severity is essential in the clinical care of rosacea
      patients and in the research on rosacea. OBJECTIVE: To determine the range of
      methods used to assess rosacea severity in clinical trials. METHODS: The medical
      literature from 1965 through 2001 was searched for rosacea clinical trials using
      MEDLINE and published citations. Forty-seven articles were reviewed. RESULTS: The
      most frequently assessed signs of rosacea were papules/pustules (43 studies),
      erythema (35), and telangiectasia (24). Other signs and symptoms of rosacea and
      adverse reactions to therapies were assessed in 27 studies. Counts of
      papules/pustules were conducted in 34 studies. Four-point scales were the most
      frequently used assessment tools for erythema (17) and telangiectasia (11). Other
      frequently used techniques included global assessment by clinicians (29) and by
      patients (21), and photography (13). CONCLUSIONS: At present, there are no
      standard validated tools for assessing the severity of rosacea or its signs or
      symptoms.

PMID- 12786871
TI  - Spectrum of idiopathic photodermatoses in a Mediterranean country.
AB  - BACKGROUND: Idiopathic photodermatoses are considered to be common disorders in
      the population of northern latitude countries, presumably because of the
      dominance of more "sun-sensitive" individuals with a light-skinned complexion.
      The incidence of these disorders in the Mediterranean or tropical countries is
      often under-appreciated because of the higher degree of perennial presence of
      sunlight and the prevalence of darker skin-type individuals who are seemingly
      more resistant to the development of sun sensitivity. METHODS: We performed a
      retrospective, chart-based review of all patients who were diagnosed with
      idiopathic photodermatoses at a photodermatology referral center in Athens,
      Greece, during a period of 10 years. Our aim was to assess the pattern of
      idiopathic photosensitivity disorders in a Mediterranean country and to determine
      their epidemiological, clinical, and photobiological profile. RESULTS: A total of
      310 patients were referred to our center with symptoms of photosensitivity. One
      hundred and forty-six patients (47.0%) were diagnosed with an idiopathic
      photosensitivity disorder by means of history, clinical examination, biochemical
      screening, histology, and phototesting. The most prevalent disorder was
      polymorphous light eruption, which was diagnosed in 95 patients (65.0%) of our
      cohort. Chronic actinic dermatitis occurred in 15 patients (10.2%), solar
      urticaria in 26 patients (17.8%), actinic prurigo in three patients (2.0%),
      hydroa vacciniforme in one patient (0.6%) and juvenile spring eruption in six
      patients (4.1%). CONCLUSIONS: Compared with the results of other studies, the
      prevalence of idiopathic photodermatoses appears to have a similar trend to that
      of higher latitude countries. Distinct features in our series include the higher
      incidence of idiopathic photosensitivity in patients with a fair-skinned
      complexion (skin types II-III) and the frequent appearance of photo-induced
      eruptions during sunny weather breaks in the winter period.

PMID- 12786872
TI  - Comparison of nickel patch test reactivity in phases of the menstrual cycle.
AB  - BACKGROUND: In earlier studies, it has been shown that severity of some diseases
      varies with menstrual cycle. Severity of skin diseases such as atopic dermatitis,
      lupus erythematosus, infections due to herpes virus, urticaria and acne were also
      reported to increase in the premenstrual phase. Effect of estradiol on the
      cellular immune system was investigated and it was found to depress the cellular
      immune response. In our study, we investigated whether nickel patch test
      reactivity was different during phases of the menstrual cycle and whether there
      was an increase in sensitivity to nickel during the premenstrual cycle in nickel
      sensitive women. METHODS: The study consisted of 30 women who had a history of
      nickel sensitivity. Finn Chamber nickel patch test was applied to all 30 women by
      dividing them into two groups of 15 and applying the test first on days 7-10 and
      then on days 20-24 of the menstrual cycle or vice versa. RESULTS: The reactions
      of both the groups on days 20-24 were more severe than those on days 7-10 even
      though the results were not statistically significant. CONCLUSIONS: Estrogens not
      only impair the skin barrier but also have a negative impact on the immune
      system. Estradiol has been proved to suppress cellular immunity. In a few studies
      conducted to date, the relationship between phases of the menstrual cycle and the
      severity of patch test reactivity has been examined with equivocal results. In
      our study, we observed that the presence of reactions due to nickel sensitivity
      was independent of the phases of the menstrual cycle. Nevertheless, we would like
      to point out the fact that the reactions seen in the second phase of the
      menstrual cycle were more severe than those seen in the first phase.

PMID- 12786873
TI  - Biting midges--those marauding "no-see-ums".

PMID- 12786874
TI  - Lung carcinoma with congenital plantar keratoderma as a variant of Clarke-Howel
      Evans syndrome.
AB  - A 32-year-old man was admitted to the Magdeburg University Hospital with icterus
      and for further diagnosis of suspected hepatitis. He also complained of
      generalized pruritus, abdominal pain, nausea, and diarrhea. The patient's history
      revealed the excision of a lymph node metastasis of the left groin showing
      pleomorphic macrocellular infiltrates, 2 months previously. The patient presented
      to our department with prominent hyperkeratosis of both feet, which had been
      present since early youth. The family history was negative. Both soles showed
      very thick, white and blackish hyperkeratosis with predominance of the heels and
      the forefeet (Fig. 1). The naturally occurring wrinkles of the skin of the toes
      were flattened. The palms were not affected, and neither was the oral mucosa.
      Further investigations revealed icterus of the sclera and multiple, firm tumors,
      which were located in the deep subcutaneous tissue, on the left hip, thigh, and
      buttock. From thorough clinical, laboratory and staging investigations, a non
      small-cell bronchogenic carcinoma, with metastases of the liver, kidneys, adrenal
      glands, and several skin sites, was diagnosed. A skin biopsy specimen of the foot
      showed substantial acanthosis of the epidermis with hypergranulosis and excessive
      orthohyperkeratosis. The corneocytes were enlarged and arranged in a tile-like
      pattern (Fig. 2). The dermis was free of inflammatory infiltrates and human
      papillomavirus infection was ruled out by immunohistochemistry. Polychemotherapy
      was immediately started with 5-fluorouracil, mitomycin, and cisplatin, which was
      well tolerated. When the patient was admitted for the second cycle, however, his
      general health had worsened markedly. He complained of abdominal pain, severe
      weight loss, and nausea. Generalized metastases showed substantial progression.
      Chemotherapy could not be continued because of a Karnowsky index below 20%. The
      patient died 2 weeks later.

PMID- 12786875
TI  - Secondary cutaneous anaplastic large cell lymphoma treated with liposomal
      doxorubicin (Doxil) leading to complete remission.

PMID- 12786876
TI  - Periorbital edema as the presenting sign of dermatomyositis.
AB  - BACKGROUND: Periorbital edema can occur in dermatomyositis, which is
      characterized by symmetric macular erythema, Gottron's papules, Gottron's sign,
      periungual telangiectasia, heliotrope rash, and poikilodermatous macules on the
      shoulders, arms, or upper back (shawl sign). CASE REPORT: We report the case of
      an 81-year-old man with dramatic periorbital edema. It was not until he was
      hospitalized with dysphagia 6 months after developing the edema that the
      diagnosis of dermatomyositis was considered. RESULTS: Laboratory tests, skin
      biopsy, and electromyography resulted in a diagnosis of dermatomyositis.
      CONCLUSIONS: Periorbital edema may appear as the presenting cutaneous
      manifestation of dermatomyositis.

PMID- 12786877
TI  - Chemotherapy induced transverse leukonychia in children.
AB  - Transverse white nail banding can be inherited or caused by various diseases and
      medications, including cancer chemotherapeutic agents, retinoids, tetracyclines,
      antimalarials, sulfonamides, pilocarpine, cortisone and zidovudine. Neither a
      specific drug nor classes of cancer chemotherapeutics were associated more
      frequently than the other with acquired transverse leukonychia in patients with
      cancer. Here we report transverse leukonychia in four children with cancer
      receiving different chemotherapeutic agents.

PMID- 12786878
TI  - A case of necrobiotic xanthogranuloma without paraproteinemia presenting as a
      solitary tumor on the thigh.

PMID- 12786879
TI  - Anaphylaxis due to burdock.

PMID- 12786880
TI  - Detection of human papillomavirus type 16 in bowenoid papulosis and nonbowenoid
      tissues.

PMID- 12786881
TI  - Lasers for facial rejuvenation: a review.
AB  - BACKGROUND: Different types of laser are used for resurfacing and collagen
      remodeling in cutaneous laser surgery. METHODS: A systematic review was performed
      of the different types of laser currently employed for skin rejuvenation. These
      systems are either ablative [high-energy pulsed or scanned carbon dioxide (CO2)
      laser emitting at a wavelength of 10,600 nm, single- or variable-pulse or dual
      ablative/coagulative mode erbium:yttrium aluminum garnet (Er:YAG) laser emitting
      at a wavelength of 2940 nm, or systems combining both 10,600 nm and 2940 nm
      wavelengths] or nonablative [Q-switched neodymium:yttrium aluminum garnet
      (Nd:YAG) laser emitting at a wavelength of 1064 nm, Nd:YAG laser emitting at a
      wavelength of 1320 nm, or diode laser emitting at a wavelength of 1450 nm].
      Different protocols, patient selection, treatment techniques, and complications
      are discussed for each system. RESULTS: New-generation CO2 resurfacing lasers
      have been successful in the treatment of photodamaged skin and scarring, with a
      postoperative morbidity dependent on the depth of thermal damage. Because of its
      minimal penetration, the pulsed Er:YAG laser, usually used in the treatment of
      more superficial rhytides, produces less postoperative morbidity. Novel ablative
      systems have been developed and a further understanding of laser-tissue
      interaction has led to the design of nonablative systems for the treatment of
      rhytides, scarring, and photodamaged skin, the efficacy and profile of which
      remain to be evaluated in the long term. CONCLUSIONS: There are several effective
      techniques for scar revision and the treatment of aged skin, but all have their
      drawbacks due to a lack of precise depth control and unwanted damage to the lower
      layers of the dermis. The Er:YAG laser is the treatment of choice for fine lines
      and superficial scars, whereas the CO2 laser is better for deeper rhytides and
      scars. In the future, a combination of lasers may be used for facial
      rejuvenation.

PMID- 12786882
TI  - One century of dermatology in Lebanon.

PMID- 12786883
TI  - The role of gabapentin in treating diseases with cutaneous manifestations and
      pain.
AB  - BACKGROUND: Gabapentin was first approved by the FDA in 1993 as an add-on
      treatment for partial epileptic seizures. In May of 2002, it was approved as
      treatment for post-herpetic neuralgia by the Food and Drug Administration. It
      appears to be a promising agent in the treatment of pain, alterations of
      sensation and pruritus associated with dermatological disease, but no review of
      these uses exists. METHODS: Medline and Google searches were performed for the
      words "Gabapentin" and "Neurontin." The articles found were reviewed. Article
      identified that contained references to the treatment of skin disease and
      neuropathic pain were examined and their contents surveyed. RESULTS:
      Approximately 1200 articles were located in Medline that referred to Garbapentin
      or Neurontin. Over 150 articles reviewed its use for neuropathic pain, neuritis
      or neuralgia of various sorts. Approximately 20 articles reviewed its use for a
      variety of dermatological conditions or diseases with dermatological
      manifestations that included: pain control associated with wound dressing
      changes, erythromelagia, piloleiomyoma related pain, brachioradial pruritus,
      Glossodynia, vulvodynia, and reflex sympathetic dystrophy. Over 100 articles that
      related to Gabapentin side effects were reviewed. CONCLUSIONS: Gabapentin is a
      very promising medication in the treatment of post-herpetic neuralgia and pain.
      Because dermatological patients suffer pain from painful tumors, after surgery,
      in conjunction with neuropathic ulcers, during dressing changes involving serious
      medical conditions, its applications seem manifold. Future studies must assess
      its role in the treatment of pruritus and other dermatological conditions
      involving pain or alteration of sensation.

PMID- 12786884
TI  - Herpetic whitlow during isotretinoin therapy.
AB  - Isotretinoin is an extremely valuable drug that is occasionally associated with
      well-known mucocutaneous side-effects, including cheilitis, retinoid dermatitis,
      palmoplantar desquamation, and photosensitivity. Paronychia has been reported
      rarely: only two prior cases of herpes simplex infections associated with
      isotretinoin have been previously reported. We present the first known case of
      herpetic paronychia occurring in an atopic patient while on isotretinoin therapy
      for acne.

PMID- 12786885
TI  - Acute rhabdomyolysis and myoglobinuria associated with isotretinoin treatment.

PMID- 12786886
TI  - Dextromethorphan induces multifocal fixed drug eruption.

PMID- 12786887
TI  - Quantifying the pathology of neurodegenerative disorders: quantitative
      measurements, sampling strategies and data analysis.
AB  - The use of quantitative methods has become increasingly important in the study of
      neurodegenerative disease. Disorders such as Alzheimer's disease (AD) are
      characterized by the formation of discrete, microscopic, pathological lesions
      which play an important role in pathological diagnosis. This article reviews the
      advantages and limitations of the different methods of quantifying the abundance
      of pathological lesions in histological sections, including estimates of density,
      frequency, coverage, and the use of semiquantitative scores. The major sampling
      methods by which these quantitative measures can be obtained from histological
      sections, including plot or quadrat sampling, transect sampling, and point
      quarter sampling, are also described. In addition, the data analysis methods
      commonly used to analyse quantitative data in neuropathology, including analyses
      of variance (anova) and principal components analysis (PCA), are discussed. These
      methods are illustrated with reference to particular problems in the pathological
      diagnosis of AD and dementia with Lewy bodies (DLB).

PMID- 12786888
TI  - Cutaneous breast cancer deposits show distinct growth patterns with different
      degrees of angiogenesis, hypoxia and fibrin deposition.
AB  - AIMS: We postulated that skin metastases and cutaneous local recurrences from
      breast adenocarcinoma show different growth patterns with distinct angiogenic
      profiles. METHODS AND RESULTS: Fifty-one surgically resected dermal breast cancer
      deposits were evaluated for growth pattern, E-cadherin expression, presence of
      necrosis and a fibrotic focus, fibrin deposition, carbonic anhydrase IX
      expression (CA IX), microvessel density, endothelial cell proliferation and blood
      vessel immaturity. Growth patterns were infiltrative, with carcinoma cells
      infiltrating the dermis without significant disturbance of the pre-existing
      architecture, expansive, meaning that a nodule of carcinoma cells and
      desmoplastic tissue pushed aside the pre-existing dermal structures, or mixed.
      All lobular carcinomas showed an infiltrative growth and lacked membranous E
      cadherin expression. Different growth patterns in the ductal carcinomas were not
      correlated with differences in E-cadherin expression. The presence of necrosis
      and/or a fibrotic focus and the expression of the hypoxia marker CA IX were
      significantly associated with an expansive growth. Fibrin was present in all
      expansive deposits and less frequently in the other growth patterns. There was a
      positive association between fibrin deposition, CA IX expression and microvessel
      density. The latter was significantly higher in the expansive and mixed growth
      patterns than in the infiltrative pattern. Endothelial cell proliferation was
      highest in the expansive growth pattern and was positively correlated with the
      presence of a fibrotic focus and with fibrin deposition. The maximum percentage
      of immature blood vessels was higher in the expansive and mixed growth patterns
      than in the infiltrative one. CONCLUSION: The recognition of different subgroups
      of cutaneous breast cancer deposits with different degrees of hypoxia-driven
      angiogenesis may have important implications for the usefulness of anti
      angiogenic therapy.

PMID- 12786889
TI  - Expression of maspin is up-regulated during the progression of mammary ductal
      carcinoma.
AB  - AIMS: The tumour suppressor gene maspin is reported to inhibit the motility,
      invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal
      mammary myoepithelial cells but is down-regulated during the progression of
      ductal carcinoma. However, we recently reported that maspin expression was
      frequently observed in invasive ductal carcinoma (IDC) with an aggressive
      phenotype, and it was a strong indicator of a poor prognosis. To our knowledge,
      to date, there has been no report investigating maspin expression in a large
      series of ductal carcinoma in situ (DCIS). METHODS AND RESULTS: To clarify
      whether there is down-regulation during the progression of ductal carcinoma, we
      immunohistochemically investigated the expression of maspin in 145 DCIS, 92
      invasive ductal carcinomas with a predominant intraductal component as well as 94
      usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of
      maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17
      of 92) of IDC with a predominant intraductal components. It significantly
      correlated with larger tumour size (P = 0.013; P = 0.042), higher histological
      grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005;
      P = 0.0074) in DCIS and IDC with a predominant intraductal components,
      respectively. In epithelial cells, the expression of maspin was observed in only
      one case of usual ductal hyperplasia, and all cases of atypical ductal
      hyperplasia were negative. CONCLUSIONS: These results and our previous
      investigation in which 27.4% of IDC were positive for maspin suggest that the
      expression of maspin in epithelial cells could be up-regulated during the
      progression of ductal carcinoma, and that it could be correlated with the
      acquisition of an aggressive phenotype.

PMID- 12786890
TI  - Clinicopathological associations of CD44 mRNA and protein expression in primary
      breast carcinomas.
AB  - AIMS: The purpose of this study was to examine the occurrence of CD44 isoforms in
      breast carcinomas and their role in predicting clinical outcome. METHODS AND
      RESULTS: Shock-frozen tumour tissues from 110 patients with breast carcinoma were
      examined by immunohistochemistry using antibodies directed against CD44s, v5, v6,
      v7 and v3-10. In addition, 80 of these tumours were available for quantitative
      real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of
      CD44s and CD44v6. Immunohistochemically, the positive tumours showed cytoplasmic
      and/or membranous staining with all antibodies. Staining results did not
      correlate with histological subtype, lymph node status, status of steroid
      receptors, tumour size or age. Neither was any correlation found for overall and
      disease-free survival. Quantitative real-time RT-PCR of CD44s and CD44v6,
      however, revealed that expression of CD44v6 mRNA was significantly associated
      with lower pathological grade (Pearson chi(2) test P = 0.009; linear-by-linear
      association P = 0.003). Linear-by-linear association between CD44s mRNA
      expression and lower pathological grade was also seen (P = 0.02). Survival
      analysis with the Kaplan-Meier method demonstrated that increased CD44s mRNA
      expression was significantly associated with both disease-free survival and
      overall survival (P = 0.0185 and P = 0.0344, respectively). A similar trend for
      CD44v6 mRNA expression was seen in these cases, but the difference was not
      significant. CONCLUSIONS: Quantitative real-time RT-PCR revealed clinical
      correlations of CD44s and CD44v6 mRNA expression in breast carcinomas while
      immunohistochemistry for the protein expression of CD44s and other CD44 variants
      did not. This contradictory result merits further studies concerning the clinical
      impact of CD44 molecules in breast carcinomas.

PMID- 12786891
TI  - Gastric-type mucin and TFF-peptide expression in Barrett's oesophagus is
      disturbed during increased expression of MUC2.
AB  - AIMS: Barrett's oesophagus constitutes metaplastic epithelium, often diagnosed by
      mucin histochemistry. We determined the mucins and trefoil factor family (TFF)
      peptides that were expressed in Barrett's oesophagus, in order to study changes
      in protein expression in early stages of Barrett's oesophagus development.
      METHODS AND RESULTS: Biopsy specimens of 71 Barrett's oesophagus patients were
      collected, and sections were stained for secretory mucins by histochemistry.
      Immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC, MUC5B,
      MUC6), TFFs (TFF1, TFF2, TFF3), and proliferation (Ki67). Protein expression in
      the tissue was measured semiquantitatively. MUC5AC and TFF1 showed high levels
      and strong colocalization in the surface epithelium, whereas MUC6, MUC5B and TFF3
      were found in the deeper glandular structures. TFF2 was found in both surface and
      glandular epithelium. The co-ordinate expression patterns of these six markers
      were similar to gastric antrum epithelium. MUC2 expression was ubiquitously
      associated with goblet cells within intestinal metaplasia, occurring in 68% of
      patients, and was correlated with increasing proliferation in the epithelium.
      CONCLUSIONS: Virtually all cells in Barrett's oesophagus epithelium displayed a
      secretory phenotype, demonstrating a co-ordinate gastric-type MUC and TFF
      expression. When MUC2 expression was more pronounced, the expression patterns of
      the other MUCs and the TFFs were increasingly disturbed. MUC2 expression may
      constitute a marker for early change in the phenotype of Barrett's oesophagus as
      a precancerous lesion.

PMID- 12786892
TI  - Colorectal carcinomas with high MIB-1 labelling indices but low pKi67 mRNA levels
      correlate with better prognostic outcome.
AB  - AIMS: Antibodies specific to the proliferation-associated protein pKi67 (e.g.
      Ki67, MIB-1) are routinely used in oncology to assess the proliferation index of
      tumour cells. In untransformed cells the amount of pKi67 present at any time of
      the cell cycle is strictly regulated. To achieve a better understanding of
      expression and regulation of this protein in tumour cells, we investigated both
      pKi67 mRNA and protein expression in routinely fixed and embedded tissue of
      colorectal carcinoma. METHODS AND RESULTS: We determined a median pKi67 specific
      in-situ hybridization labelling index of 42% (9-79%) and a median Ki67 index (MIB
      1 labelling index) of 59% (26-94%) in 47 resected colorectal adenocarcinomas of
      different stages and grades. In 32 cases expression of pKi67 mRNA and protein
      correlated well but we observed a significant difference between both values in
      15 tumours. In these cases more than 30% of the cells expressed the protein but
      not the mRNA of pKi67, possibly due to cell cycle arrest. Patients belonging to
      this group had a significantly (P < 0.012) better prognosis. CONCLUSIONS: Tumours
      with a high pKi67 protein level but low mRNA expression are likely to proliferate
      more slowly than calculated on the basis of their Ki67 staining index, which
      possibly explains the patients' improved outcome.

PMID- 12786893
TI  - HER2 oncogene amplification in extramammary Paget's disease.
AB  - AIMS: To study HER2 oncogene amplification and over-expression in skin samples of
      23 patients with extramammary Paget's disease (EMP). EMP is a rare intra
      epidermal adenocarcinoma, which has been reported to over-express the HER2
      oncoprotein. METHODS AND RESULTS: HER2 gene amplification, detected by
      chromogenic in-situ hybridization, was found in 43% (10/23) of the lesions. HER2
      protein over-expression (3+ immunostaining intensity) was found in 12 tumours
      (52%), including all 10 tumours with gene amplification. Two tumours showed low
      level (2+) HER2 immunostaining. Mammary Paget's lesions, which were used as
      controls, showed HER2 amplification and over-expression in all 10 cases studied.
      CONCLUSIONS: These results indicate that HER-2 protein over-expression in EMP is
      common and due exclusively to gene amplification. They open up the possibility of
      HER2-targetted immunotherapy for patients with HER2+ disease.

PMID- 12786894
TI  - E-cadherin loss rather than beta-catenin alterations is a common feature of
      poorly differentiated thyroid carcinomas.
AB  - AIMS: To investigate the immunohistochemical and molecular genetic features of
      the cadherins/catenins complex in thyroid carcinoma based on the hypothesis that
      poorly differentiated carcinoma of the thyroid represents an intermediate step
      between well-differentiated and undifferentiated carcinomas. METHODS AND RESULTS:
      Immunohistochemistry for E-, P- and N-cadherins and alpha-, beta- and gamma
      catenins was performed in a series of 17 cases of poorly differentiated carcinoma
      of the thyroid. All cases showed absence of membranous expression of E-cadherin
      with no aberrant expression of P- or N-cadherins; regarding catenins there was
      heterogeneous loss of expression with membranous immunolocalization of the three
      catenins in most cases. Molecular analysis of the E-cadherin gene and exon 3 of
      the beta-catenin gene was also performed by polymerase chain reaction/single
      strand conformation polymorphism and sequencing. No mutations in either gene were
      detected in any case. CONCLUSIONS: In contrast to previous reports, our results
      suggest that loss of E-cadherin rather than beta-catenin mutation is the crucial
      event in determining the differentiation 'level' of thyroid carcinomas.

PMID- 12786895
TI  - Calponin and h-caldesmon expression in synovial sarcoma; the use of calponin in
      diagnosis.
AB  - AIMS: To assess the frequency of expression and potential diagnostic utility of
      calponin and caldesmon in synovial sarcomas. METHODS AND RESULTS:
      Immunohistochemistry with antibodies to calponin and h-caldesmon was undertaken
      in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of
      which one biphasic and eight monophasic tumours had poorly differentiated areas),
      10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous
      tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and
      neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and
      five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for
      calponin in spindle and glandular areas, nine in spindle cells only, and one in
      glands only. All monophasic synovial sarcomas and poorly differentiated areas
      expressed calponin; in monophasic tumours this was focally (29% of cases),
      moderately (39%), or diffusely (32%) positive and the poorly differentiated areas
      were usually moderately or diffusely positive. Four synovial sarcomas showed
      focal reactivity for h-caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT,
      4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H
      caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5
      fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative
      in the other small round cell tumours. CONCLUSIONS: Calponin can be used as an
      additional marker for synovial sarcoma. Its absence argues against the diagnosis.
      The presence of calponin might be useful in distinguishing poorly differentiated
      synovial sarcoma from other small round cell tumours. H-caldesmon is not helpful
      in diagnosis of synovial sarcoma.

PMID- 12786896
TI  - Haemorrhagic dermatomyofibroma (plaque-like dermal fibromatosis):
      clinicopathological and immunohistochemical analysis of three cases resembling
      plaque-stage Kaposi's sarcoma.
AB  - AIMS: Dermatomyofibroma (plaque-like dermal fibromatosis) represents a distinct
      clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms
      showing a myofibroblastic line of differentiation. These benign neoplasms occur
      frequently, but not exclusively, in young women, and the shoulder girdle as well
      as the upper trunk are common locations. Histologically, dermatomyofibroma is
      characterized by a plaque-like proliferation of cytologically bland spindle
      shaped tumour cells containing an ill-defined, pale eosinophilic cytoplasm and
      elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles
      orientated parallel to the skin surface, adnexal structures are spared and
      elastic fibres are increased and fragmented. Immunohistochemically, tumour cells
      express vimentin and variably muscle actin and alpha-smooth muscle actin, but are
      negative for desmin, CD34, S100, and epithelial markers. The main differential
      diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma),
      pilar leiomyoma, neurofibroma, adult myofibromatosis, extra-abdominal
      fibromatosis and plaque-stage dermatofibrosarcoma protuberans. METHODS AND
      RESULTS: We report three cases of dermatofibroma arising in male patients aged
      31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions
      were completely excised and no local recurrence has been reported.
      Histologically, the neoplasms showed classical features of dermatomyofibroma;
      however, in addition abundant extravasated erythrocytes, scattered inflammatory
      cells, numerous capillaries, and sieve- and slit-like spaces, features resembling
      plaque-stage Kaposi's sarcoma, were noted. In none of the cases did spindled
      tumour cells stain positively for CD34, and HHV8 was not detected by polymerase
      chain reaction. CONCLUSIONS: The reported cases widen the clinicopathological
      spectrum of dermatomyofibroma and emphasize plaque-stage Kaposi's sarcoma as an
      additional differential diagnosis.

PMID- 12786897
TI  - Ossifying fibromyxoid tumour of soft parts, with focus on unusual
      clinicopathological features.
AB  - AIMS: Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the
      soft tissues of proximal limbs/girdle, or head and neck. Histologically, it
      usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid
      matrix with a characteristic peripheral ossification. However, we present two
      cases that deviated from this pattern. MATERIAL AND METHODS: One tumour, which
      was removed from the axilla of a 55-year-old female, was unusual in its large
      size (120 mm in diameter) and in its restriction of bone formation to its central
      zones. The other tumour, which occurred in a 62-year-old female, was remarkable
      in its acral location on the hand and high mitotic activity (four mitoses per
      high-power field). These features caused concern and follow-up of the patients
      was recommended. So far there have been no recurrences (25 and 18 months after
      surgery, respectively). An additional previously undescribed feature was the
      presence of fibronexus-like structures by electron microscopy in the second case.
      However, a myofibroblastic phenotype was not supported by the immunohistochemical
      findings. CONCLUSION: Though a distinct entity, ossifying fibromyxoid tumour may
      exhibit a wider clinicopathological spectrum than generally recognized.

PMID- 12786898
TI  - Plasmablastic lymphoma in HIV+ patients: an expanding spectrum.
AB  - AIM: To describe an unusual human immunodeficiency virus (HIV)-associated
      lymphoma in uncommon sites. Plasmablastic lymphoma is a distinctive HIV
      associated tumour that was first described in the jaws and oral cavity. Only two
      cases (stomach and lung) have been documented in extra-oral sites. MATERIALS AND
      METHODS: Four cases were encountered in HIV+ patients: three in the anorectal
      region and one which was nasal and paranasal. The cases were routinely processed
      and immunohistochemistry was performed on formalin-fixed paraffin-embedded
      tissue. RESULTS: The cases showed the typical morphological appearances of a high
      grade, blastic non-Hodgkin's lymphoma (brisk mitotic activity and tingible body
      macrophages). In addition, some cells had a plasmacytoid appearance and
      paranuclear clearing. Immunophenotypically, the tumour cells were negative for
      LCA, CD20 and CD45RA. However, a small proportion of cells (5%) were
      immunoreactive for CD79a and the majority were positive with VS38c, indicative of
      plasma cell differentiation. Kappa light chain and IgG heavy chain restriction
      was also detected. CONCLUSIONS: Plasmablastic lymphoma may occur in extra-oral
      sites and has a characteristic immunophenotype including focal expression of CD31
      by the neoplastic cells. Awareness of the absence of expression of conventional B
      cell markers and its presence in unusual sites should facilitate the diagnosis of
      plasmablastic lymphoma in HIV+ patients.

PMID- 12786899
TI  - Basal cell adenocarcinoma in minor salivary glands.
AB  - Basal cell adenocarcinoma is a rare and relatively recently characterized
      malignant salivary gland tumour, the malignant counterpart of basal cell adenoma.
      Diagnosis depends on finding features similar to adenoma but with an infiltrative
      growth pattern and exclusion of adenoid cystic carcinoma, sialoblastoma and
      basaloid squamous carcinoma. Basal cell adenocarcinoma is very rarely reported in
      minor salivary glands. We report three cases of basal cell adenocarcinoma
      affecting the labial, buccal and palatal minor salivary glands. One recurred
      following complete removal but with lesional disruption and further local wide
      excision appeared curative. A further lesion failed to recur in 5 years' follow
      up despite marginal excision and a third after 3 years' follow-up. Basal cell
      adenocarcinoma is considered a low-grade malignancy, and in the minor glands wide
      excision and radiotherapy are recommended. However, the reported lesions appear
      to have a more indolent behaviour than previously reported lesions in minor
      glands.

PMID- 12786900
TI  - Perineal nodular induration: the 'third testicle of the cyclist', an under-
      recognized pseudotumour.

PMID- 12786901
TI  - Intrasplenic mucinous cystadenoma with mesenchymal stroma arising in pancreatic
      heterotopia.

PMID- 12786902
TI  - Stages of normal and aberrant intrahepatic bile duct development in a mixed
      hepatoblastoma.

PMID- 12786903
TI  - VE-cadherin in perineuriomas.

PMID- 12786904
TI  - Pulmonary sclerosing haemangioma diagnosed by frozen section.

PMID- 12786905
TI  - The role of the information specialist in the systematic review process: a health
      information case study.
AB  - There is an increasing body of literature on the information specialist's role in
      supporting evidence-based health care. In particular, the information component
      in systematic reviews has received considerable attention in recent years.
      Information professionals have evolved from simply acting as 'evidence locators'
      and 'resource providers' to being quality literature filterers, critical
      appraisers, educators, disseminators, and even change managers. This paper
      describes ten possible roles for information professionals in the systematic
      review process, using a case study of a review of the health information needs of
      visually impaired people carried out by the Centre for Health Information
      Management Research (CHIMR) at the University of Sheffield. This health
      information review was undertaken entirely by a team of information
      professionals. The ten roles identified are: project leader, project manager,
      literature searcher, reference manager, document supplier, critical appraiser,
      data extractor, data synthesiser, report writer and disseminator. This review has
      also identified an eleventh possible role for information professionals; that of
      primary researcher. Finally, the implications for evidence-based health care and
      evidence-based health informatics are discussed.

PMID- 12786906
TI  - Embedding knowledge management in the NHS south-west: pragmatic first steps for a
      practical concept.
AB  - Knowledge management, like clinical governance, is a practical science. Clinical
      governance, with its emphasis on creating an environment where clinical quality
      is monitored and acted upon, is one of the foundation stones of the new National
      Health Service (NHS). Both knowledge management and clinical governance need to
      share the same criteria in order to operate. Using these two pragmatic concepts
      and the premise of a practical approach, this article seeks to identify the
      drivers for knowledge management in the NHS, highlight national initiatives and
      focus on the steps libraries in the south-west of England have taken to make
      knowledge management a reality. In so doing, the central role of the library and
      information service has been reinforced and embedded and librarians have been
      recognized for their real worth to their organizations.

PMID- 12786907
TI  - Incorporating the views of obstetric clinicians in implementing evidence
      supported labour and delivery suite ward rounds: a case study.
AB  - OBJECTIVES: To implement evidence-supported delivery suite ward rounds using
      strategies to overcome barriers. DESIGN: Qualitative case study to identify
      barriers and a quantitative assessment of outcomes on ward rounds. METHOD: After
      an introduction to the proposed evidence-supported delivery suite ward round
      reactions were elicited from 15 clinicians. Responses were categorized into
      barriers related to knowledge, skills, attitudes and behaviour. Using strategies
      to overcome these barriers, a weekly evidence-supported ward round was
      established. During patient-centred discussions, clinical questions were
      formulated. Following literature searches, evidence was acquired and appraised.
      RESULTS: Clinicians had limited awareness about the potential benefits of a
      clinical librarian's support during ward rounds. They were unsure of their skills
      in evidence-based practice. There was scepticism, fear of loss of autonomy, poor
      motivation and resistance to change. Clinicians identified several factors that
      could impinge on their practice. Using appropriate strategies when evidence
      supported ward rounds were conducted, 67 questions were raised. However only
      seven articles were appraised in time to affect decisions on that ward round.
      CONCLUSIONS: Knowledge of barriers was helpful in developing plans for
      implementation of evidence-supported ward rounds. The pilot study indicates the
      feasibility of this approach.

PMID- 12786908
TI  - Non use of health information kiosks examined in an information needs context.
AB  - Whilst great emphasis has rightly been placed on the increased availability and
      use of health information, little research has been undertaken into the non use
      of such material, particularly with regard to electronic sources. Computer
      transactional log data from health information touch screen kiosks, collected as
      part of an ongoing Department of Health-funded study being carried out by City
      University, showed that females in the 55-74 age group were particularly under
      represented as users. To explore reasons for this, in-depth interviews were
      carried out with 13 non-kiosk-using, primary-care out-patients fitting this
      profile, at a surgery which had a kiosk that was being monitored. Subjects were
      interviewed at length about their information needs and information-seeking
      behaviour, to determine reasons (if any) they might have had for non-kiosk use.
      The study utilized an interview schedule and technique loosely based on the
      'Sense-Making' methodology of Brenda Dervin (Talk Presented at the International
      Communication Association Annual Meeting, May 1983, Dallas, Texas, USA. Available
      from: http://communicationsbsohio-stateedu/sense-making/art/artdervin83html.).
      Findings elicited many factors accounting for non use of the system. The first
      and major source of information remained the doctor, with written or other
      sources only being consulted where recommended or provided. There was evidence
      that patients wanted little more than the minimum information or instructions
      required to deal with their condition. Many appeared unaware of the presence of
      the kiosk and others assumed either that it was not for patient use or that it
      would not serve their needs. The methodology proved itself, with certain caveats,
      to be an appropriate vehicle for this kind of exploratory work.

PMID- 12786909
TI  - The consortium site license: is it a sustainable model?

PMID- 12786910
TI  - Special features of electronic journals: do physicians want them?

PMID- 12786911
TI  - Personal reflections on the role of librarians in the teaching of evidence-based
      healthcare.

PMID- 12786912
TI  - Using research in practice.

PMID- 12786913
TI  - Learning and teaching.

PMID- 12786918
TI  - Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To assess whether, in children, oral magnesium oxide reduces
      migrainous headache frequency, severity, and associated features compared to
      placebo. BACKGROUND: There is no single, safe, widely well-tolerated, and
      effective prophylactic treatment for all children and adolescents with frequent
      migrainous headache. DESIGN: Randomized, double-blind, placebo-controlled,
      parallel-group trial. METHODS: This study was conducted between June 1997 and
      January 2000 using 7 selected Northern California Kaiser Permanente sites. We
      recruited children of ages 3 to 17 years who reported a 4-week history of at
      least weekly, moderate-to-severe headache with a throbbing or pulsatile quality,
      associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with
      sleep, but no fever or evidence of infection. Subjects were randomly assigned to
      receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day
      with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of
      headache days (days with at least one headache) during each of eight 2-week
      intervals was chosen to be the primary outcome variable. RESULTS: Of those
      enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44
      placebo); 74 of 192 eligible subjects declined to participate. Baseline
      information on demographic factors, health status, and headache history was
      similar comparing the 2 groups. By intention-to-treat analysis, we found a
      statistically significant decrease over time in headache frequency in the
      magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although
      the slopes of these 2 lines were not statistically significantly different from
      each other (P =.88). The group treated with magnesium oxide had significantly
      lower headache severity (P =.0029) relative to the placebo group. CONCLUSIONS:
      This study does not unequivocally determine whether oral magnesium oxide is or is
      not superior to placebo in preventing frequent migrainous headache in children,
      but treatment with the active agent did lead to a significant reduction in
      headache days. Larger trials involving this safe, appealing complementary therapy
      are needed.

PMID- 12786919
TI  - Prolonged benign exertional headache. The Vaga Study of headache epidemiology.
AB  - OBJECTIVE: To explore in detail the duration of exertional headache attacks and
      explicitly to identify cases of prolonged exertional headache. BACKGROUND: The
      prevalence of exertional headache in general population samples may exceed 10%.
      The prevalence and distinguishing clinical characteristics of prolonged
      exertional headache are not well delineated. METHODS: One author (O.S.)
      personally interviewed 1838 parishioners (88.6%) of ages 18 to 65 years living in
      a southern Norwegian commune. Questions relevant to exertional headache were
      included. RESULTS: As recently reported elsewhere, exertional headache was
      present in 12.3% of those questioned. With 1 hour set as a tentative border for
      short- versus long-duration exertional headache, there were approximately equal
      numbers with short- and long-lasting attacks; prevalence of short-lasting attacks
      was 6.3% and long-lasting attack prevalence was 6.0%. In regards to other
      epidemiologic and clinical features, the long-lasting cases did not seem to
      deviate from the short-lasting cases; both categories had a moderate female
      preponderance and similar age of onset. There was a somewhat higher mean number
      of "migrainelike features" in the long-lasting than in the short-lasting variety
      of exertional headache. Exertional headache attacks could last up to 24 hours.
      CONCLUSIONS; There seems to be little reason to subdivide exertional headache
      into 2 separate varieties according to attack duration. Exertional headache
      attacks have "migrainelike" features but do not seem to be "form fruste" migraine
      attacks. The long-lasting variety is not uncommon.

PMID- 12786920
TI  - Abnormal neuromuscular transmission in cluster headache.
AB  - OBJECTIVE: To identify and investigate any dysfunction of neuromuscular
      transmission in episodic cluster headache. BACKGROUND: Abnormal neuromuscular
      transmission has been shown in migraine with aura and in migraine without aura by
      using single fiber electromyography. Especially for migraine with aura, a genetic
      cause has been postulated. Episodic cluster headache is a primary headache
      disorder in which genetic factors may, at times, play a strong role. METHODS:
      Single fiber electromyography during voluntary contraction of the extensor
      digitorum communis muscle, nerve conduction studies of upper and lower
      extremities, and concentric needle electromyography of the extensor digitorum
      communis were performed on 6 patients with episodic cluster headache and 6 age
      matched normal controls. Twenty potential pairs were recorded from each subject.
      Twenty individual jitter values and a mean jitter value were calculated for each
      subject. Both mean individual jitter values and numbers of abnormal individual
      jitter values were compared in patients with cluster headache versus normal
      controls. RESULTS: Three of 6 patients with episodic cluster headache showed
      pronounced neuromuscular transmission abnormalities by single fiber
      electromyography. None of the controls had any neuromuscular transmission
      abnormality. Another patient with episodic cluster headache had borderline
      dysfunction of neuromuscular transmission. Transmission was clearly normal in
      only 2 of 6 patients with cluster headache. CONCLUSION: These results suggest
      that episodic cluster headache may share the same abnormality of neuromuscular
      transmission observed in migraine.

PMID- 12786921
TI  - Impact of a group-based model of disease management for headache.
AB  - OBJECTIVES: To assess the impact of a group-based model of disease management for
      patients with headache. BACKGROUND: Despite advances in the acute and preventive
      treatment of migraine, many patients with headache remain misdiagnosed and
      undertreated. Models of care that incorporate principles of disease management
      may improve headache care. DESIGN AND METHODS: This was a prospective, open
      label, observational study. Patients with headache were referred by physicians or
      identified from emergency department records. Patients attended a group session
      led by a registered nurse practitioner, and later had follow-up consultation.
      Charts and computer records were reviewed to document triptan costs and headache
      related visits for 6 months before and after the intervention. Changes in
      headache frequency and severity were assessed. RESULTS: Triptan costs for 264
      patients and chart review for 250 were available. Six-month triptan costs
      increased $5423 US dollars(19%), headache-related visits were reduced by 32%, and
      headache-related emergency department visits were reduced by 49%. Severe headache
      frequency was reduced in 62 (86%) of 72 patients who initially had severe
      headaches more than 2 days per week. Patients identified by emergency department
      screening accounted for 21% of the study group, 31% of the baseline triptan
      costs, and 46% of the baseline visits. For the entire study group, reduced visits
      yielded a net savings of $18,757 US dollars despite increased triptan costs.
      CONCLUSIONS: Implementation of this group-based model produced a reduction in
      emergency department and clinic visits, significant clinical improvement, a small
      increase in pharmacy costs, and overall cost reduction. The greatest improvement
      in each outcome measure was seen in patients most severely afflicted at baseline.
      Our results suggest that the principles of disease management may be applied
      effectively to a headache population, with a positive financial impact on a
      managed care organization.

PMID- 12786922
TI  - Assessing the severity of migraine: development of the MIGSEV scale.
AB  - OBJECTIVES: To identify items that serve to assess the severity of migraine with
      a high level of clinical and psychometric relevance and to combine these into a
      unitary severity scale. BACKGROUND: Severity of migraine is an important
      determinant of patient quality of life and of health care resource utilization.
      Despite this, no validated method exists for measuring migraine severity.
      METHODS: After selection from the medical literature items of potential relevance
      to the severity of migraine, consensus meetings led to a choice of items which
      subsequently were refined further on the basis of patient interviews. The
      psychometric properties of those items then were assessed in a survey involving
      287 migraineurs. The methods used to test reliability and validity included test
      retest, calculation of Cronbach alpha coefficient, analysis of factorial
      structure using principal components analysis, a comparison of the agreement
      between doctors' and patients' assessments, and correlation with a validated
      quality-of-life questionnaire. The most pertinent items revealed by the factorial
      analysis were combined in a unitary scale. RESULTS: Seven items reflecting
      severity were identified by expert consensus. These were intensity of pain,
      tolerability, disability in daily activities, presence of nausea or vomiting,
      resistance to treatment, duration of attacks, and frequency of attacks. Principal
      components analysis identified 3 dimensions accounting for 65% of the overall
      variance related to intensity of attacks, resistance to treatment, and frequency
      of attacks. The internal consistency and the reproducibility of the items
      appeared quite satisfactory, and variations in these items were correlated with
      quality-of-life scores. The 4 items related to intensity of attacks were combined
      into a single scale with 3 response modalities. CONCLUSIONS: The 3 dimensions
      identified by this investigation appeared medically relevant and to have good
      psychometric properties. The items on the intensity dimension can be used to
      generate a simple scale for assessing migraine attack severity.

PMID- 12786923
TI  - Editorial comment.

PMID- 12786924
TI  - Factors associated with burden of primary headache in a specialty clinic.
AB  - OBJECTIVE: To examine factors associated with social, occupational, and
      psychological burden of common primary headache (migraine and tension-type
      headache). BACKGROUND: The personal and social burden of primary headache is
      high. Health, occupational, social, and psychological factors contributing to
      burden in people with disabling headache have not been fully unravelled. METHODS:
      One hundred eighty consecutive patients with either migraine or tension-type
      headache attending a specialty headache outpatient clinic for the first time were
      evaluated over a 9-month period. Headache subtype was operationally defined
      according to International Headache Society criteria. Headache frequency,
      duration, and severity were recorded. Occupational and social disability were
      quantified using the Migraine Disability Assessment questionnaire. Psychological
      burden was quantified using the 28-item General Health Questionnaire, the Beck
      Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid
      vulnerability to life stress was quantified using the neuroticism subscale of the
      Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache
      scored higher on the Migraine Disability Assessment questionnaire and had higher
      Beck Depression Inventory and General Health Questionnaire depression scores than
      those with less frequent (episodic) headache. Frequency of headache, but not pain
      severity, duration, or diagnosis, predicted both Migraine Disability Assessment
      total disability and General Health Questionnaire/Beck Depression Inventory
      depression. Neuroticism was predictive of depression but not disability. Patients
      with chronic migraine had the highest depression and disability scores.
      CONCLUSION: The number of days per month with headache is a key determinant of
      headache-related burden in those attending specialty clinics. Frequent (chronic)
      headache is associated with significantly higher psychopathology scores and
      general social impairment, but the direction of this relationship is not clear.
      Those with migraine and chronicity are the most impaired.

PMID- 12786925
TI  - Reduced impact of migraine in everyday life: an observational study in the Dutch
      Society of Headache Patients.
AB  - OBJECTIVE: To explore the percentage of patients who report a reduced impact of
      migraine on their life, and to which factors this improvement can be attributed.
      METHODS: Four hundred forty-eight members of the Dutch Society of Headache
      Patients answered a set of structured questionnaires, including the Migraine
      Specific Quality of Life instrument (MSQOL). RESULTS: Of this group, 70% reported
      a reduced impact of migraine. The most frequently reported reason for this
      reduction was a change in medication (77%); in particular, change to a triptan.
      Other favorable factors included a change in life-style (56%): 42% of patients
      reported more relaxed coping with migraine, a reduction of stress in general
      (28%) and of stress related to work (24%), and leading a more regular life-style
      (21%). In addition, social support was frequently mentioned, particularly that
      offered by the Dutch Society of Headache Patients (58%), family (46%), and their
      general practitioner (28%). The patients who reported a reduced impact of
      migraine had less migraine attacks and a higher quality of life than those who
      did not report such a reduction. CONCLUSION: The results confirm that factors
      that are proven effective in clinical trials on migraine also have these effects
      outside a formal experimental environment.

PMID- 12786926
TI  - Differences in anger expression between individuals with and without headache
      after controlling for depression and anxiety.
AB  - OBJECTIVE: To evaluate whether anger and anger expression are different between
      persons with and without headache after controlling for depression and anxiety.
      BACKGROUND: Persons with headache may experience more problems with anger and its
      expression when compared with persons without headache. It is important to
      establish whether differences exist for persons with and without headache on
      trait anger and anger expression independent of depression and anxiety. To date,
      however, this issue has received little attention in the empirical literature.
      The current study measured trait anger, anger-in, hostility, anxiety, and
      depression among persons with and without headache, and evaluated whether trait
      anger and anger-in differentiated groups independent of depression and anxiety.
      METHODS: Participants were 422 adults recruited from a larger study within a
      university setting. Of those, 171 suffered from headache (mean age, 21 years; 81%
      were female; 69% were white; mean years with pain, 7.53). Another 251 sex-matched
      individuals (mean age, 21 years; 81% female; 62% white) met criteria for the
      headache-free group. Participants provided information regarding their headache
      characteristics and were administered affective trait measures (Trait version of
      the State-Trait Anxiety Inventory, Brief Symptom Inventory-Depression), trait
      anger measures (Trait Anger Scale, Cook-Medley Hostility Scale), and a measure of
      the extent to which individuals hold their anger in. RESULTS: Multivariate
      analysis of variance revealed significant differences between the 2 groups (Wilks
      lambda =.86, P <.001, eta2 =.14). Step-down analysis revealed that even after
      controlling for all other variables, those in the headache group had higher
      levels of anger-in (P <.001, eta2 =.08; mean, 18.98 versus 15.68). Trait anger
      and hostility did not differ between groups after controlling for depression and
      anxiety. Logistic regression revealed that anger-in contributed most to
      predicting headache status (P <.001; partial r =.23). CONCLUSIONS: The current
      findings indicate that persons with headache hold their anger in more than those
      without headache even after controlling for levels of trait anger, depression,
      and anxiety. However, after controlling for depression and anxiety, individuals
      no longer differed on trait anger. Also, anger-in was the strongest predictor of
      headache. The current findings suggest that holding anger in is more common among
      headache sufferers. Given recent findings regarding the negative effect of
      holding anger in among persons with pain conditions, this may be an important
      factor to evaluate when considering psychological/emotional factors affecting
      headache.

PMID- 12786927
TI  - Visual distortion provoked by a stimulus in migraine associated with
      hyperneuronal activity.
AB  - BACKGROUND: Migraineurs with visual aura are highly susceptible to illusions and
      visual distortion and are particularly sensitive to a pattern of regularly spaced
      parallel lines or stripes. PURPOSE: To determine whether the high degree of
      susceptibility to illusions and visual distortion in migraineurs with aura is
      associated with hyperneurological activity of the occipital cortex. METHODS: In
      order to investigate any relationships among neuronal activity, spatial frequency
      of square-wave gratings, and self-described visual distortion, we investigated
      the neuronal and psychophysical responses to square-wave gratings in migraineurs
      with visual aura and in nonheadache controls. RESULTS: Square-wave gratings
      provoked various types of visual distortion and illusions and induced a
      hyperneuronal response in the visual cortex of migraineurs with visual aura, a
      response that strongly depended upon the stimulus spatial frequency. CONCLUSION:
      The hyperneuronal activity of the occipital cortex is consistent with general
      cortical hyperexcitability in migraine.

PMID- 12786928
TI  - Clinical characteristics of patients with comorbidity of migraine and epilepsy.
AB  - OBJECTIVE: Neuronal hyperexcitability might explain the comorbidity of migraine
      and epilepsy. Spreading depression, a postulated pathophysiological mechanism of
      epileptic seizures and migraine with aura, may hypothetically be the link between
      the disorders in these comorbid conditions. The aim of the present study was to
      determine whether certain clinical characteristics associated with spreading
      depression are overrepresented in patients with comorbidity. METHODS: In an
      outpatient clinic-based series, clinical characteristics of 61 patients with a
      comorbidity of migraine and epilepsy were compared to those of 280 patients with
      epilepsy alone and 248 patients with migraine alone. Patients were interviewed
      with a standardized questionnaire. RESULTS: The proportion of females was
      significantly higher in patients with comorbidity and patients with migraine as
      compared to patients with epilepsy (P <.001). Comparing patients with epilepsy
      and comorbidity, the frequency of epilepsy syndromes and seizure types was not
      significantly different. Comparing patients with migraine and comorbidity,
      migraine with aura was significantly more frequent in patients with comorbidity
      (P =.019). Other migraine features such as moderate to severe pain intensity,
      worsening of pain on activity, phonophobia, and photophobia were significantly
      more frequent in patients with comorbidity as compared to patients with migraine
      (P < or =.001). CONCLUSION: No specific epileptic characteristics could be found
      in patients with comorbidity. Altered cerebral excitability resulting in an
      increased occurrence of spreading depression may explain the differences in
      migraine attacks in patients with comorbidity as compared to patients with
      migraine alone.

PMID- 12786929
TI  - Congenital predisposition to spontaneous intracranial hypotension: a case report.
AB  - Dural rupture, cerebrospinal fluid leakage, and spontaneous intracranial
      hypotension may complicate significant or minimal spinal trauma and cause chronic
      headache with a positional component. While such cases typically reflect no pre
      existing predilection, we encountered a patient whose cervicothoracic anatomy
      appeared to predispose him to this complication.

PMID- 12786930
TI  - Postural headache and cerebrospinal fluid leak: believing is seeing.
AB  - A 33-year-old woman developed persistent postural headache following epidural
      anesthesia (L2-L3 level). Iohexol myelography (L5-S1 puncture) demonstrated no
      epidural extravasation of contrast material (Figure A), but subsequent computed
      tomography (CT) axial images (B, C) revealed leakage of dye through the needle
      track of the L5-S1 puncture (arrows). No leakage of contrast medium was found at
      the site of the L2-L3 epidural puncture.

PMID- 12786931
TI  - Botulinum toxin injections for headache.

PMID- 12786933
TI  - Cervicogenic headache in children.

PMID- 12786934
TI  - The non-nocebo response: can migraine medication efficacy be enhanced?

PMID- 12786935
TI  - Migraine-induced stroke in a patient with migraine-related epilepsy.

PMID- 12786936
TI  - More on migraine and coronary artery disease.

PMID- 12786937
TI  - The truth about frovatriptan.

PMID- 12786941
TI  - Different roles of proteolipids and 70-kDa subunits of V-ATPase in growth and
      death of cultured human cells.
AB  - BACKGROUND: The vacuolar-type proton-translocating adenosine triphosphatase (V
      ATPase) plays important roles in cell growth and tumour progression. V-ATPase is
      composed of two distinct structures, a hydrophilic catalytic cytosolic sector
      (V(1)) and a hydrophobic transmembrane sector (V(0)). The V(1) sector is composed
      of 5-8 different subunits with the structure A(3)B(3)C(1)D(1)E(1)F(1)G(1)H(1).
      The V0 sector is composed of 5 different subunits with the structure
      1161381191166. The over-expression of 16-kDa proteolipid subunit of V-ATPase in
      the perinuclear region of the human adventitial fibroblasts promotes phenotypic
      modulation that contributes to neointimal formation and medial thickening. A
      relationship between oncogenicity and the expression of the 16-kDa proteolipid
      has also been suggested in human pancreatic carcinoma tissue. RESULTS: We found
      that the mRNA levels of the 16-kDa proteolipid but not of the 70-kDa subunit of V
      ATPase in human myofibroblasts were more abundant in serum-containing medium
      (MF(+) cells) than serum-free medium (MF(-) cells). In HeLa cells, the levels of
      mRNA and protein of the 16-kDa, 21-kDa or 70-kDa were clearly suppressed when the
      corresponding anti-sense oligonucleotides were administered to the culture
      medium. The growth rate and viability (mostly due to necrosis) of HeLa cells were
      reduced markedly by the 16-kDa and 21-kDa anti-sense, but little by the 70-kDa
      anti-sense, and not at all by any sense oligonucleotides. The localization of 16
      kDa/21-kDa proteolipid subunits was different from that of the 70-kDa subunit in
      HeLa cells. CONCLUSION: These results suggest that the 16-kDa and 21-kDa
      proteolipid subunits of the V0 sector play crucial roles in growth and death of
      cultured human cells. Our results may provide new insights into the mechanism and
      therapeutic implications for vessel wall hyperplasia and tumorigenesis.

PMID- 12786940
TI  - Facial pain with recurrent facial palsy.

PMID- 12786942
TI  - Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL
      1beta: a role for the dual signalling pathways, Akt and Erk.
AB  - BACKGROUND: Matrix metalloproteinases including MMP-9 mediate matrix destruction
      during chronic inflammatory diseases such as arthritis and atherosclerosis. MMP-9
      up-regulation by inflammatory cytokines involve interactions between several
      transcription factors including activator protein-1 and NFkappaB. The upstream
      regulatory pathways are less well understood. RESULTS: To search for the
      mechanism of tissue destruction in the process of inflammatory disorders, we
      investigated the signalling pathway critical for the activation of MMP-9
      expression and secretion by IL-1beta. Treatment of Balb 3T3 cells with IL-1beta
      activated MMP-9 transcription and subsequent secretion in a time- and dose
      dependent manner. Concomitantly, IL-1beta treatment of cells activated
      phosphorylation of Akt, Erk and p38. Treatment of cells with either LY294002, a
      PI3K inhibitor, or expression of a dominant negative form of Akt drastically
      suppressed the IL-1beta-dependent secretion of MMP-9. Pretreatment of cells with
      a MEK1 inhibitor, U0126, also strongly inhibited IL-1beta-dependent secretion of
      MMP-9. In contrast, pre-treatment with a specific p38 kinase inhibitor, SB203580,
      had no effect on IL-1beta-dependent secretion of MMP-9. In addition, cells
      expressing constitutively active form of Akt or MEK1 showed no clear activation
      of MMP-9 secretion, whereas these cells responded well to IL-1beta treatment.
      However, co-transfection of cells with both active Akt and MEK1 was sufficient to
      induce MMP-9 secretion without stimulation with IL-1beta. CONCLUSION: Taken
      together, our results suggest that IL-1beta stimulation of cells activates MMP-9
      secretion by the activation of the dual signalling pathways, the PI3K-Akt and
      MEK1-Erk and constitutive activation of these pathways were sufficient to induce
      MMP-9 secretion.

PMID- 12786943
TI  - Transmembrane topology of sphingoid long-chain base-1-phosphate phosphatase,
      Lcb3p.
AB  - BACKGROUND: Sphingoid long-chain base-1-phosphates (LCBPs) are thought to act as
      intracellular signalling molecules in yeast. Lcb3p is a member of the LCBPs
      specific phosphatase family (SPP family). Other yeast phosphatases, Lpp1p and
      Dpp1p, are members of a different lipid phosphatase family (LPP family) known to
      exhibit broader substrate specificities. Until now, only the membrane topology of
      mammalian LPP family members has been reported, whereas that of the SPP family
      has remained unclear. RESULTS: In our in vitro system, Lcb3p displayed major
      phosphatase activity against dihydrosphingosine-1-phosphate, while Dpp1p and
      Lpp1p also exhibited activities. Here, we determined that Lpp1p and Dpp1p exhibit
      the topology common to the LPP family. Moreover, we examined the transmembrane
      topology of Lcb3p using a C-terminal reporter approach. From our results we
      deduced a structural model illustrating that Lcb3p has eight membrane-spanning
      domains with its highly conserved phosphatase motifs positioned within the
      endoplasmic reticulum (ER) lumen. Consistent with this result, Lcb3p collected in
      low speed pellet fractions was highly resistant to exogenous proteinase K unless
      the membrane was disrupted. CONCLUSION: Our results suggest that the active site
      of Lcb3p is located in the ER lumen and, thus, the phosphate group of the LCBP is
      hydrolysed on the lumenal side.

PMID- 12786944
TI  - A novel rabconnectin-3-binding protein that directly binds a GDP/GTP exchange
      protein for Rab3A small G protein implicated in Ca(2+)-dependent exocytosis of
      neurotransmitter.
AB  - BACKGROUND: Rab3A, a member of the Rab3 small G protein family, regulates Ca2+
      dependent exocytosis of neurotransmitter. The cyclical activation and
      inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A
      is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP) and GTP
      Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).
      We have recently found a novel protein, named rabconnectin-3, which is co
      immunoprecipitated with Rab3 GEP or GAP from the extract of the crude synaptic
      vesicle (CSV) fraction of rat brain. Rabconnectin-3 is abundantly expressed in
      the brain where it is associated with synaptic vesicles. We have found that two
      more proteins are co-immunoprecipitated with Rab3 GEP from the CSV fraction of
      rat brain. We attempted here to isolate and characterize one of them. RESULTS: We
      determined its partial amino acid sequence, cloned its cDNA from a human cDNA
      library, and determined its primary structure. The protein consisted of 1490
      amino acids (aa) and showed a calculated molecular weight of 163808. The protein
      had 7 WD domains. The protein was abundantly expressed in the brain where it co
      localized with rabconnectin-3 on synaptic vesicles. The protein formed a stable
      complex with rabconnectin-3. We named this protein rabconnectin-3beta and renamed
      rabconnectin-3 rabconnectin-3alpha. Rabconnectin-3beta, but not rabconnectin
      3alpha, directly bound Rab3 GEP. Neither rabconnectin-3alpha nor -3beta directly
      bound Rab3 GAP. CONCLUSION: These results indicate that rabconnectin-3 consists
      of the alpha and beta subunits and binds directly Rab3 GEP through the beta
      subunit and indirectly Rab3 GAP through an unidentified molecule(s).

PMID- 12786945
TI  - Overlapping omt1+ and omt2+ genes are required for spore wall maturation in
      Schizosaccharomyces pombe.
AB  - BACKGROUND: Overlapping genes that are transcribed from the same genomic regions
      are rare in eukaryotes and to date few detailed functional analyses have been
      reported. RESULTS: We report here three novel overlapping transcripts that are
      specifically expressed during meiosis of Schizosaccharomyces pombe. They are
      denoted as omt1+, omt2+ and omt3+ after overlapping meiotic transcripts. omt1+
      encodes a 12-kDa protein and omt2+ encodes a 11-kDa protein with homology to the
      bifunctional mammalian protein DCoH/PCBD. omt3+ does not have a significant open
      reading frame. The omt2+ transcript overlaps with both the omt1+ and omt3+
      transcripts but the latter two transcripts do not overlap. omt1Delta and
      omt2Delta but not omt3Delta failed to form mature spore walls. The Omt1-GFP and
      Omt2-GFP fusion proteins localized to the outside and the inside of the spore
      walls, respectively. The sporulation-specific protein Meu10 and the spore wall
      components were abnormally localized in the spore walls of omt1Delta and
      omt2Delta. CONCLUSION: The overlapping genes omt1+ and omt2+ express functional
      proteins that participate in spore wall maturation, indicating that gene overlap
      does not affect the physiological functions of the proteins encoded by these
      genes. Generation of overlapped RNA may be due to loose regulation of
      transcription termination during meiosis of S. pombe.

PMID- 12786946
TI  - Terminal deoxynucleotidyltransferase forms a ternary complex with a novel
      chromatin remodeling protein with 82 kDa and core histone.
AB  - BACKGROUND: Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase that
      enhances the Ig and TcR gene diversity in the N region at the junctions of
      variable (V), diversity (D) and joining (J) segments in B- and T-cells. TdT
      synthesizes the N region in concert with many proteins including DNA-PKcs, Ku70
      and Ku86. To elucidate the molecular mechanism of the N region synthesis, we
      first attempted to isolate the genes with products that directly interact with
      TdT. RESULTS: Using a yeast two-hybrid system, we isolated a cDNA clone encoding
      a novel nuclear protein that interacts with TdT. This protein was designated as
      TdT interacting factor 2 (TdIF2). The confined region of the C-terminal in TdIF2
      is involved in specific interaction with the entire C-terminal in TdT. TdIF2
      contains an acidic region comprised of 42 residues. TdIF2 was shown to bind
      specifically to a core histone by pull down assay using specific antibodies
      against TdIF2. When a TdT/TdIF2 complex was applied on to a DNA-cellulose column,
      only TdT bound to the column while TdIF2 passed through. TdIF2 reduces the TdT
      activity to 46% of its maximum value in vitro assay system using activated DNA as
      primer. CONCLUSIONS: TdIF2 binds directly to TdT and core histone. Furthermore,
      TdT, TdIF2 and core histone form a ternary complex. TdIF2 liberates H2A/H2B from
      a core histone in correlation with PCNA. The enzymatic consequence of the
      TdIF2/TdT complex is the reduction of TdT activity in vitro. TdIF2 would function
      as a chromatin remodeling protein at the N region synthesis.

PMID- 12786947
TI  - Masseter thickness, endurance and exercise-induced pain in subjects with
      different vertical craniofacial morphology.
AB  - The aim of the study was to compare neuromuscular features of the masseter muscle
      in subjects with different vertical craniofacial morphology. Fifteen short-faced
      (mandibular plane-Frankfurt plane angle < 15 degrees) and 15 normal- to long
      faced (mandibular plane-Frankfurt plane angle > or = 23 degrees) male students
      participated. The thickness of the masseter was assessed by ultrasonography.
      Onset and endurance of exercise pain were recorded during sustained biting at a
      level of 15% of maximum voluntary contraction and 30 micro V electromyographic
      activity. Pain and fatigue was measured on visual analog scales before and after
      the biting, as well as before and after 10 min chewing. Statistical comparison
      showed that the masseter muscle was significantly thicker (+15%) in the short
      faced than the normal- to long-faced subjects. The pain onset time and endurance
      time were also consistently shorter in short-faced subjects, whereas the
      intensity of pain and fatigue did not differ significantly between the two
      groups. Multiple stepwise regression showed positive influence from the
      mandibular plane inclination and the masseter thickness on the pain onset time
      and endurance time. The present findings support the concept that subjects with
      different craniofacial morphology show neuromuscular differences.

PMID- 12786948
TI  - Effects of maxillary sinus floor elevation surgery on maxillary sinus physiology.
AB  - In a prospective study, the effects of elevation surgery of the maxillary sinus
      floor on maxillary sinus physiology were assessed. Seventeen consecutive patients
      without preoperative anamnestic, clinical and radiological signs of maxillary
      sinusitis underwent sinus floor elevation surgery with iliac crest bone grafts.
      All patients were subjected to unilateral endoscopic examination of the maxillary
      sinus, taking of a biopsy specimen from the sinus floor mucosa, and collection of
      a sinus lavage-fluid aspirate. This triad of evaluations was performed
      immediately preceding the elevation procedure, and 3 months (at implant
      insertion) and 9 months (at uncovering of implants) postoperatively. All
      procedures were performed under general anesthesia. Preoperatively, three out of
      17 patients showed pre-existing mucosal pathology endoscopically, while the 3-
      and 9-month results revealed the presence of mucosal pathology in four and two
      patients, respectively. The 3-month microbiological evaluation showed a
      significant increase in cultures with bacterial growth, while the 9-month culture
      results were comparable to the preoperative status of the maxillary sinus.
      Morphologically, neither fibrosis nor an altered inflammatory response or
      thickening of the epithelium and lamina propria was observed postoperatively. The
      number of goblet cells in the epithelial layer was increased. From this study it
      is concluded that the effect of maxillary sinus floor elevation surgery with
      autogenous bone grafts does not appear to have clinical consequences in patients
      without signs of pre-existing maxillary sinusitis.

PMID- 12786949
TI  - Elevated levels of collagen cross-link residues in gingival tissues and
      crevicular fluid of teeth with periodontal disease.
AB  - Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen cross-link
      residues. Lysylpyridinoline is present in most tissues, whereas LP is present
      mainly in mineralized tissue. Both are elevated in tissue with increased collagen
      resorption. The purpose of this investigation was to assess if the concentrations
      of LP and HP are elevated in gingiva and gingival crevicular fluid (GCF) of teeth
      with advanced periodontitis (AP). We investigated human gingival biopsies of
      healthy teeth (n = 19) and teeth with AP (n = 43) in 49 individuals. Samples of
      GCF from 54 teeth with AP were collected in seven patients and compared with
      samples from 11 patients with experimentally induced gingivitis. Levels of LP and
      HP were measured by HPLC and fluorescence detection. Gingival concentrations of
      HP but not LP around teeth with advanced periodontitis were significantly
      elevated compared with teeth with healthy periodontium. While significant amounts
      of HP and LP were measurable in the GCF of teeth with AP, no HP and LP was
      identified 3 months following non-surgical periodontal therapy of the teeth or in
      fluid from teeth subjected to experimentally induced gingivitis. Elevated
      concentrations of HP and LP in GCF may serve as indicators of ongoing destruction
      of periodontal tissues and alveolar bone in advanced periodontitis.

PMID- 12786950
TI  - Salivary IgA in response to periodontal treatment.
AB  - There is evidence that the quantity of antigen load is crucial for the activation
      of IgA immune responses. In order to investigate the relevance of these findings
      in aggressive periodontitis, salivary antibody responses were measured during non
      surgical and antibiotic treatment. Twenty-one patients with generalized
      aggressive periodontitis were monitored for total salivary IgA and IgA reactive
      to Porphyromonas gingivalis in resting and stimulated whole saliva. Non-surgical
      treatment included full-mouth professional tooth cleaning and subgingival scaling
      and root planing (SRP) under local anesthesia. Patients were recalled at 3 months
      and 6 months following systemic antibiotic treatment. Non-parametric statistics
      showed significant improvements in the clinical parameters in all patients.
      Between baseline and 4 wk following SRP, median concentrations of total IgA
      decreased both in resting (-46%) and in stimulated (-33%) saliva. The P.
      gingivalis-specific IgA activity showed a twofold increase at 4 wk after SRP. In
      addition to these changes, periodontal treatment of aggressive periodontitis did
      not appear to affect salivary IgA, and there were no significant correlations of
      IgA to the clinical parameters. In conclusion, salivary IgA responses during
      periodontal treatment were not found to have a diagnostic or prognostic
      significance.

PMID- 12786951
TI  - Serum-mediated release of leukotoxin from the cell surface of the periodontal
      pathogen Actinobacillus actinomycetemcomitans.
AB  - The leukotoxin of the periodontopathogen Actinobacillus actinomycetemcomitans is
      an important virulence factor that lyses human neutrophils and monocytes and
      thus, it may enable the bacterium to evade the local host defense. The toxin also
      induces degranulation of neutrophils and cytokine release in monocytes. To
      trigger these biological activities, leukotoxin has to be released from the
      bacterium and diffuse into the periodontal tissues. To date, the conditions found
      to cause toxin release have been artificial and have included high ion
      concentration and alkaline conditions. To study the release of the toxin under
      conditions mimicking the natural environment of the periodontium the ability of
      human serum to enable leukotoxin release from the bacterial surface was examined.
      Suspensions of leukotoxic A. actinomycetemcomitans strains were incubated with
      various concentrations of human serum or serum albumin. The suspensions were
      centrifuged and the leukotoxin in the supernatants or the cell pellets was
      detected by gel electrophoresis and immunoblotting. Serum was found to cause the
      rapid release of leukotoxin from the bacteria in a concentration-dependent
      manner. Pure albumin exhibited a similar effect. The leukotoxin released was
      active against human neutrophils. Only a minor proportion of it was associated
      with membranous vesicles produced by the bacteria. The results indicate that
      serum, a fluid closely related to the exudate in inflamed periodontal pockets,
      releases leukotoxin from the cell surface of A. actinomycetemcomitans. The
      process may enable the diffusion of the toxin from the bacterial biofilm into the
      surrounding tissues, where it can exert its biological effect.

PMID- 12786952
TI  - Interaction of triclosan with eukaryotic membrane lipids.
AB  - The possibility that triclosan and PVM/MA (polyvinylmethyl ether/maleic acid)
      copolymer, additives to dentrifrices, could interact with eukaryotic membrane
      lipids was studied by two methods: first, by determining the pressure/molecular
      area isotherms at 37 degrees C of glycerophospholipid monolayers, using the
      Langmuir technique; and second, by phase-transition parameters in liposomes of
      the same lipids, using differential scanning calorimetry (DSC). Triclosan
      interacted, in a concentration-independent manner, with monolayers of saturated
      phosphatidylcholines (PC; i.e. markers of the outer membrane leaflet of
      eukaryotic cells). Triclosan and PVM/MA copolymer mixtures were shown to clearly
      interact in a concentration-dependent manner with PC. Triclosan was found to
      interact with liposomes of saturated and unsaturated phosphatidylcholines and
      phosphatidylserines (PS; i.e. markers of the inner membrane leaflet of eukaryotic
      cells), and saturated ethanolamines (PE; i.e. markers of the inner membrane
      leaflet of eukaryotic cells), resulting in a decrease of the lipid melting
      temperature (Tm). PVM/MA copolymer changed the Tm of PS, PC, and PE in different
      manners. By adding PVM/MA or triclosan-PVM/MA copolymer mixtures to 1-stearoyl-2
      oleoyl-sn-glycero-3-phosphoserine (SOPS) no lipid transitions were detected. A
      biphasic change of the PC transition temperature resulted when triclosan or
      triclosan PVM/MA copolymer mixtures were added, indicating domain formation and
      change of the lipid polymorphism.

PMID- 12786953
TI  - The effects of a triclosan/copolymer dentifrice on oral bacteria including those
      producing hydrogen sulfide.
AB  - A clinical procedure was developed to examine the effects of short-term and
      extended use of a triclosan/copolymer dentifrice and a commercial fluoride
      dentifrice on oral bacteria, including those producing hydrogen sulfide. Healthy
      adults volunteered for this double-blind, crossover design clinical study and
      provided saliva samples for culturing on enriched and indicator media to
      enumerate all salivary bacteria and those producing hydrogen sulfide
      (odorigenic), respectively. Subjects brushed with an assigned dentifrice for 7 d
      and were sampled on day 8 to assess the long-term effects on bacteria. Extended
      use of the triclosan/copolymer dentifrice resulted in a 49% and 66% reduction of
      salivary and odorigenic bacteria, respectively, compared with the fluoride
      dentifrice. To examine short-term effects, subjects subsequently brushed with
      their assigned dentifrice and were sampled at 2 h and 4 h post-brushing. At 2 h
      and 4 h post-brushing, the triclosan/copolymer dentifrice resulted in a 62% and
      52% decrease for salivary bacteria and 79% and 72% decrease for odorigenic
      bacteria, respectively, vs. the fluoride dentifrice. The results indicate a
      significant decrease of all salivary bacteria and hydrogen sulfide-producing
      odorigenic bacteria following use of the triclosan/copolymer dentifrice and
      explain previous results on the efficacy of this dentifrice on oral malodor.

PMID- 12786954
TI  - Effect of lipopolysaccharides on vascular endothelial growth factor expression in
      mouse pulp cells and macrophages.
AB  - Vascular endothelial growth factor (VEGF), a potent pro-angiogenic factor, might
      regulate the neovascularization observed in the pulp of teeth with deep caries.
      The purpose of this in vitro study was to evaluate the effect of bacterial
      lipopolysaccharides (LPS) on VEGF expression in dental pulp cells. Mouse
      odontoblast-like cells (MDPC-23) or undifferentiated pulp cells (OD-21) were
      exposed to 0-20 microg ml-1Escherichia coli LPS or 0-80 microg ml-1Prevotella
      intermedia LPS. As controls, mouse macrophages or gingival fibroblasts were
      exposed to LPS, since these cells are known to secrete VEGF. The VEGF expression
      was evaluated by reverse transcriptase polymerase chain reaction or enzyme-linked
      immunosorbent assay. The baseline expression levels of VEGF protein were higher
      in MDPC-23 and OD-21 than in fibroblasts or macrophages. Vascular endothelial
      growth factor protein expression was upregulated in MDPC-23 and macrophages
      exposed to E. coli LPS, but not in OD-21 cells or fibroblasts. Higher
      concentrations of P. intermedia LPS were required to induce VEGF expression in
      MDPC-23 cells. Treatment with LPS did not affect VEGF expression at the mRNA
      level in any of the cells evaluated. These results demonstrate that bacterial LPS
      upregulates VEGF expression in odontoblast-like cells and macrophages, and
      suggest that the regulation of VEGF expression occurs primarily at a post
      transcriptional level.

PMID- 12786955
TI  - Dentin sialoprotein isoforms: detection and characterization of a high molecular
      weight dentin sialoprotein.
AB  - Dentin sialoprotein (DSP) is a glycoprotein accounting for 5-8% of the dentin non
      collagenous proteins. The cDNA sequence predicts that rat DSP has 13 potential
      casein kinase phosphorylation sites and six potential N-linked glycosylation
      sites. However, its total phosphorylation level, as well as the nature and
      locations of the carbohydrate moieties, are unknown. Our findings in the present
      study show that rat DSP has 6.2 phosphates per molecule and that the majority of
      carbohydrates are attached to the protein through N-linked glycosylations. During
      our separation of dentin non-collagenous proteins with ion-exchange
      chromatography, we observed high molecular weight components eluting late in the
      salt gradient that were recognized by anti-DSP antibodies. We have purified these
      high molecular weight components using a monoclonal anti-DSP antibody affinity
      column. Data from amino acid analysis, phosphate level measurements and Edman
      degradation of tryptic peptides unequivocally proved that the very acidic, high
      molecular weight components are isoforms of DSP (designated HMW-DSP).
      Deglycosylation analysis indicates that the slower migration rate of HMW-DSP on
      SDS-PAGE results from its higher level of carbohydrate modifications.

PMID- 12786956
TI  - Dentin caries activity status related to hardness and elasticity.
AB  - This research tested the hypothesis that active and arrested carious dentin
      lesions have distinct structural characteristics and differ in atomic force
      microscopy-based nano-mechanical properties of the identifiable zones found in
      hydrated coronal carious lesions. Eight carious molars were used in this study.
      After longitudinally bisecting all the samples through the centers of carious
      lesions, they were divided into two subgroups: moderately active caries and
      arrested caries. The samples were highly polished and stained by caries detector,
      which allowed identification of four zones: pink, light pink, transparent and
      apparently normal. The mechanical properties were studied wet using atomic force
      microscopy. The results show that both groups contained the same zones,
      regardless of activity status, and different zones have different mechanical
      properties. Generally, the more demineralized outer zones (pink, light pink) were
      larger and the mechanical properties of the zones were lower for moderately
      active caries. For arrested caries, the transparent zone occupied a larger
      portion of the lesion and the reduced elastic modulus was not significantly
      different from the underlying normal zone, although its hardness was lower than
      the apparently normal zone.

PMID- 12786957
TI  - Erosion-inhibiting effect of sodium fluoride and titanium tetrafluoride treatment
      in vitro.
AB  - The prevention of dental erosion with fluoride is still largely unknown
      territory. It was the aim of this study to determine the erosion-inhibiting
      effect of topical neutral 1% sodium fluoride (NaF) application and an application
      of a 4% titanium tetrafluoride (TiF4) solution compared with no treatment. Ten
      bovine incisors were selected and three enamel samples prepared from each tooth.
      One sample from each tooth was assigned to one of three experimental groups. The
      experimental treatments were: no fluoride application (control); 4 min
      application of neutral 1% NaF gel; and 4 min application of 4% TiF4 solution. All
      of the specimens were repeatedly exposed to 50 mm citric acid solution containing
      0.4 mm CaCl2, and 2.2 mm KH2PO4 at pH 3.0 over four consecutive days. The acid
      exposure was performed in intervals and the intensity was increased over the days
      of the experiment. Enamel dissolution was determined by calcium content
      measurement of the acid solution after exposure, using atomic absorption
      spectroscopy. A statistically significant erosion-inhibiting effect was found for
      both NaF and TiF4 treatments compared with the control group from an erosion
      exposure time of 3 min. The reduction of calcium loss, however, was higher for
      the TiF4-treated specimens than the NaF-treated. From 16 min of erosion exposure,
      the erosion-inhibiting effect was significantly stronger in the TiF4 than the NaF
      group. The relative reduction of calcium loss compared with the control group
      remained stable for the TiF4 group, whereas for the NaF group the relative
      reduction decreased with cumulative erosion time. It is concluded that topical
      TiF4 application provides a potential treatment option in erosion prevention.

PMID- 12786958
TI  - Human enamel dissolution in citric acid as a function of pH in the range 2.30< or
      =pH< or =6.30--a nanoindentation study.
AB  - The objective of this study was to investigate the dissolution of human enamel in
      citric acid solutions over a wide range of pH. The in vitro conditions are
      considered to be relevant to soft drink-induced enamel erosion. Nanoindentation
      was used to investigate changes in the nanomechanical properties of polished
      enamel surfaces after exposure to citric acid solutions. Solutions used had 38.1
      mmol l-1 citric acid and pH greater than 2.3 but less than 6.3 (2.30 < or = pH <
      or = 6.30). Samples were exposed to rapidly stirred, constant composition
      solutions for 120 s. Statistically significant changes in enamel hardness and
      reduced elastic modulus were observed after exposure to all solutions. There was
      an approximately linear dependence of enamel hardness on solution pH for 2.90 <
      or = pH < or = 6.30. Below pH 2.90, enamel is thought to have reached the lowest
      possible hardness value. The reduction in enamel dissolution caused by an
      increase in pH of a soft drink is likely to be small. Product modification to
      reduce the erosive potential of drinks may require additional methods such as
      addition of calcium salts.

PMID- 12786959
TI  - Identification of organic eluates from four polymer-based dental filling
      materials.
AB  - Elution from polymer-based dental filling materials may have a potential impact
      on the biocompatibility of the materials. Since information from the
      manufacturers about ingredients in the materials often is incomplete, analyses of
      eluates from the materials are necessary for a better knowledge about possible
      harmful compounds. The aim of this study was to identify organic eluates from
      polymerized samples of two composites, one compomer and one resin-reinforced
      glass ionomer cement. Samples were immersed in ethanol or Ringer's solution.
      Organic leachables were analyzed by gas chromatography-mass spectrometry.
      Identification was confirmed with reference substances, if available. Among
      components detected were monomers, co-monomers, initiators, stabilizers,
      decomposition products and contaminants. Thirty-two substances were identified
      and 17 were confirmed with reference substances. From elution in Ringer's we
      identified 13 eluates from Tetric Ceram, 10 from Z250, 21 from Dyract and six
      from Fuji II LC; HEMA, HC and CQ were found in all samples. From elution in
      ethanol 12 eluates from Tetric Ceram, 18 eluates from Z250, 19 from Dyract and 10
      from Fuji II LC were identified. The diversity of eluates from the four materials
      under study is demonstrated. Owing to variation between the materials, the
      biocompatibility including the allergenic potential may be different.

PMID- 12786960
TI  - Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of
      oligodontia.
AB  - Tooth development is regulated through a series of reciprocal interactions
      between the dental epithelium and mesenchyme and requires protein products of a
      number of genes. It has been reported that selective tooth agenesis is associated
      with mutations in human MSX and PAX9 genes. Mutational analysis of the two genes
      was performed in 25 individuals with familial or sporadic form of permanent tooth
      agenesis. Single-stranded conformational polymorphism analysis revealed no
      mutations in the entire coding sequence of the MSX1 gene. In PAX9, a novel,
      heterozygous G151A transition in the sequence encoding the paired domain of the
      PAX9 protein was detected in a patient with agenesis of third molars, second
      premolars and incisors, but not in her parents, the remaining patients or 162
      individuals with normal dentition. This is the first de novo mutation described
      in PAX9. Our results support the view that mutations in PAX9 could constitute a
      causative factor of oligodontia. We hypothesize that the G151A transition in PAX9
      might be responsible for the sporadic form of tooth agenesis in this patient.

PMID- 12786961
TI  - Polymer structure of a light-cured resin composite in relation to distance from
      the surface.
AB  - The aim of the investigation was to study the polymer structure of a light-cured
      resin composite in relation to the distance from the irradiated surface. Ten
      cylinders (4 x 8 mm) of composite were light-cured in a mold at 580 mW cm-2 for
      40 s. The cylinders were expressed from the mold and, after 1 wk of dry storage
      at 37 degrees C, embedded in dental stone. Grinding parallel to the long axis of
      the cylinders on carborundum paper exposed the resin composite. The Wallace
      hardness in relation to distance from the irradiated surface was measured before
      and after 1 d of ethanol storage. Before ethanol storage and at distances from
      the surface of 0.5-3.5 mm, no difference in hardness was recorded. The ethanol
      storage gave rise to a softening of the resin composite. The softening recorded
      at 3.0-3.5 mm was significantly more pronounced than the softening taking place
      at 0.5-2.5 mm. This result was explained by a slower polymerization occurring at
      the greater distances from the irradiated surface, resulting in a polymer with
      reduced crosslink density.

PMID- 12786962
TI  - Risk factors in periodontitis and classifying the disease.

PMID- 12786965
TI  - Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen
      induced spine synapse formation on hippocampal CA1 pyramidal cells of female
      rats.
AB  - Oestrogen is known to influence pyramidal cell spine synapse plasticity in the
      CA1 subfield of the hippocampus. Apart from direct oestrogen action on the
      hippocampus, oestrogen effects mediated by subcortical structures are known to be
      important. The purpose of this study was to investigate whether the medial septum
      diagonal band of Broca (MSDB) takes part in mediating oestrogen effects to the
      hippocampus. Special attention was given to the role of cholinergic MSDB neurons
      that project to the hippocampus, as a rather large population of them contains
      oestrogen receptors and, consequently, may be sensitive to oestrogen signals.
      Adult female rats were ovariectomized. Oestradiol- and cholesterol-filled
      cannulae (control) were implanted into the MSDB. To selectively eliminate the
      cholinergic population of MSDB neurons of oestrogen-treated animals, a group of
      rats was injected with 192 IgG-saporin (SAP) into the lateral ventricle 1 week
      before the cannula implant. Immunostaining with anti-choline acetyltransferase
      and parvalbumin (PA) showed that cholinergic but not PA-containing GABAergic
      neurons were substantially reduced in the MSDB of SAP rats. Comparative electron
      microscopic unbiased stereological analysis on the spine synapse density of CA1
      area pyramidal cells was performed between all animal groups. Rats that received
      oestradiol-filled cannulae showed a higher (30%) spine synapse density than
      control animals. Oestrogen-treated rats that had received SAP treatment showed no
      significant difference to controls. Thus, this observation indicates that septo
      hippocampal cholinergic neurons are involved in mediating oestrogen effects to
      the hippocampus. The relevance of this observation to mnemonic functions and
      Alzheimer's disease is discussed.

PMID- 12786966
TI  - Insulin-like growth factor-I as a promoting factor for cerebellar Purkinje cell
      development.
AB  - In the mammalian CNS, the peptide hormone insulin-like growth factor-I (IGF-I) is
      synthesized in a certain subset of neurons and, it has been suggested, serves as
      a local neurotrophic factor. A postnatal increase in the expression of IGF-I and
      the type-1 IGF receptors (IGFR1) in the cerebellar cortex and its related brain
      regions indicates that developing cerebellar Purkinje cells (PC) may be an
      important target of IGF-I. However, little is known about how IGF-I influences PC
      development. Here we addressed this question, using a reduced environment of
      cerebellar neuron culture derived from perinatal mice. IGF-I exogenously applied
      at a physiological concentration (10 nm) greatly promoted the dendritic growth
      and survival of the PCs. By contrast, IGF-I only slightly promoted the somatic
      growth and little affected the maturation of the electrophysiological
      excitability of the PCs. The closely related hormone insulin had weaker promoting
      effects than did IGF-I. IGF-I appeared to at least bind to IGFR1 and to up
      regulate the signalling pathways involving the phosphoinositide 3-kinase (PI3-K),
      mitogen-activated protein kinase (MAPK), p38 kinase (p38K), and an unknown
      signalling molecule(s). These signalling pathways may be coupled to the
      individual aspects of PC development in different manners and this may explain
      the difference in effects of IGF-I among these aspects. These findings suggest
      that IGF-I serves as a promoting factor for PC development, particularly
      postnatal survival and dendritic growth.

PMID- 12786967
TI  - D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young
      rats.
AB  - Large amounts of d-2-hydroxyglutaric acid (DGA) accumulate in d-2-hydroxyglutaric
      aciduria (D-2-OHGA), an inherited neurometabolic disorder characterized by severe
      neurological dysfunction and cerebral atrophy. Despite the significant brain
      abnormalities, the neurotoxic mechanisms of brain injury in this disease are
      virtually unknown. In this work, the in vitro effect of DGA on various parameters
      of oxidative stress was investigated; namely chemiluminescence, thiobarbituric
      acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential
      (TRAP), total antioxidant reactivity (TAR) and the activities of the antioxidant
      enzymes catalase, glutathione peroxidase and superoxide dismutase in cerebral
      cortex from 30-day-old-rats. DGA significantly increased chemiluminescence and
      TBA-RS and decreased TAR values in the cortical supernatants. In contrast, TRAP
      and the antioxidant enzyme activities were not altered by the metabolite.
      Furthermore, the DGA-induced increase of TBA-RS was fully prevented by the free
      radical scavengers ascorbic acid plus Trolox (water-soluble alpha-tocopherol) and
      attenuated by the inhibitor of nitric oxide synthase Nomega-nitro-L-arginine
      methyl ester (L-NAME), suggesting the role of superoxide, hydroxyl and nitric
      oxide radicals in this action. The data indicate a stimulation of lipid
      peroxidation through the production of free radicals and a reduction of the brain
      capacity to efficiently modulate the damage associated with the enhanced
      generation of free radicals by DGA. In the case that these findings also occur in
      human D-2-OHGA, it is feasible that oxidative stress may be involved in the
      pathophysiology of the brain injury observed in patients with this disease.

PMID- 12786968
TI  - Two distinct calcium-sensitive and -insensitive PKC up- and down-regulate an
      alpha-bungarotoxin-resistant nAChR1 in insect neurosecretory cells (DUM neurons).
AB  - While there is mounting knowledge about the structure and diversity of insect
      neuronal nicotinic acetylcholine receptors, less attention has been directed
      towards their intracellular regulation by calcium-mediated activation or
      inhibition of protein phosphorylation. The main goal of this work was to
      delineate the chain of molecular events that lead to the up- and down-regulation
      by two protein kinase Cs of an insect neuronal alpha-bungarotoxin-resistant
      nicotinic acetylcholine receptor (called nAChR1). The native nicotinic
      acetylcholine receptor intracellular regulation was studied on dissociated adult
      dorsal unpaired median neurons isolated from the terminal abdominal ganglion of
      the cockroach Periplaneta americana using whole-cell patch-clamp technique and
      calcium imaging. We report that under 0.5 micro malpha-bungarotoxin treatment,
      the inward current produced by pressure ejection application of nicotine onto the
      cell body was differentially sensitive to specific protein kinase C activators
      and inhibitors. The phorbol ester PMA produced a calcium-dependent increase in
      current amplitude blocked by chelerythrine. By contrast, the diacylglycerol
      analogue 1,2-dioctanoyl-sn-glycerol produced a calcium-independent reduction of
      the nicotinic response, reversed by rottlerin and chelerythrine. This indicated
      that two protein kinase C isozymes ('classical' and 'novel' protein kinase C,
      named PKC1 and PKC2, respectively) up- and down-regulated nicotinic acetylcholine
      receptor function. PMA and 1,2-dioctanoyl-sn-glycerol effects were mimicked by
      pirenzepine-sensitive M1 muscarinic receptor subtype coupled to phospholipase C
      second messenger pathway. Low concentration of muscarine elevated internal
      calcium levels, which thereby activated PKC1. By contrast, a high concentration
      of muscarine strongly increased [Ca 2+]i, which induced inhibition of PKC1. This
      effect was reversed by FK506, suggesting the implication of PP2B which unmasked
      PKC2 activity mediating down-regulation of nicotinic acetylcholine receptor.

PMID- 12786969
TI  - Alterations in the intrauterine environment by glucocorticoids modifies the
      developmental programme of the auditory system.
AB  - Prenatal exposure to excessive glucocorticoids alters the programming of the
      metabolic and endocrine balance of various organs, including the nervous system.
      In the present study, prenatal glucocorticoid treatment was shown to increase the
      susceptibility of the inner ear to acoustic noise trauma in adult life. Acute
      auditory brainstem response thresholds were not different between the age-matched
      groups. However, when measured at 48 h and 4 weeks postexposure, the
      dexamethasone (DEX)-treated rats showed little or no recovery from the trauma. In
      contrast, normal rats showed a significant amount of recovery by 48 h
      postexposure and continued to show further recovery over 4 weeks. In addition,
      acoustic trauma resulted in a massive outer hair cell loss in the DEX rats
      compared to minor loss in the normal rats. To determine whether oxidative stress
      plays a role in the recovery phase of acoustic trauma, the free radical scavenger
      PBN (100 mg/kg) was administered before, during and several times after noise
      exposure. PBN treatment significantly reduced the physiological and morphological
      cochlear differences which were observed between DEX and control rats after
      acoustic trauma. These data support the hypothesis that alterations in the
      intrauterine environment may modify the developmental programme of the cochlea,
      inducing dysfunction later in adult life. Excessive prenatal exposure to
      dexamethasone decreased the potential for recovery of the cochlea to oxidative
      stress induced by acoustic trauma; this decreased recovery potential can be
      counteracted by treatment with antioxidants.

PMID- 12786970
TI  - Enriched environment and physical activity stimulate hippocampal but not
      olfactory bulb neurogenesis.
AB  - Exposure to an enriched environment and physical activity, such as voluntary
      running, increases neurogenesis of granule cells in the dentate gyrus of adult
      mice. These stimuli are also known to improve performance in hippocampus
      dependent learning tasks, but it is unclear whether their effects on neurogenesis
      are exclusive to the hippocampal formation. In this study, we housed adult mice
      under three conditions (enriched environment, voluntary wheel running and
      standard housing), and analysed proliferation in the lateral ventricle wall and
      granule cell neurogenesis in the olfactory bulb in comparison to the dentate
      gyrus. Using bromodeoxyuridine to label dividing cells, we could not detect any
      difference in the number of newly generated cells in the ventricle wall. When
      giving the new cells time to migrate and differentiate in the olfactory bulb, we
      observed no changes in the number of adult-generated olfactory granule cells;
      however, voluntary running and enrichment produced a doubling in the amount of
      new hippocampal granule cells. The discrepancy between the olfactory bulb and the
      dentate gyrus suggests that these living conditions trigger locally through an as
      yet unidentified mechanism specific to neurogenic signals in the dentate gyrus.

PMID- 12786971
TI  - Metabotropic glutamate receptor 5 (mGluR5)-mediated phosphoinositide hydrolysis
      and NMDA-potentiating effects are blunted in the striatum of aged rats: a
      possible additional mechanism in striatal senescence.
AB  - The aim of the present work was to verify whether an impairment of subtype 5
      metabotropic glutamate receptor-mediated neurotransmission did occur in the aged
      striatum. To this end, the ability of the subtype 5 metabotropic glutamate
      receptor agonist, RS-2-chloro-5-hydroxyphenylglycine, to stimulate
      phosphoinositide hydrolysis and to potentiate N-methyl-d-aspartate-induced
      effects in striatal slices from young (3 months) and aged (24 months) rats was
      compared. The ability of RS-2-chloro-5-hydroxyphenylglycine to induce maximal
      phosphoinositide turnover and to potentiate N-methyl-d-aspartate effects was
      significantly reduced in slices from old vs. young rats. These changes were
      associated with a significant reduction in the expression of subtype 5
      metabotropic glutamate receptor protein (-28.8%) and phospholipase C-beta1 (
      55.8%) in old striata, while receptor messenger ribonucleic acid expression was
      unchanged. These results show that the signalling associated with subtype 5
      metabotropic glutamate receptors undergoes significant age-related changes and
      that a reduced expression of subtype 5 metabotropic glutamate receptors and, more
      importantly, phospholipase C-beta1 may account for the functional decline of
      subtype 5 metabotropic glutamate receptors.

PMID- 12786972
TI  - Differential effect of dopamine deficiency on the expression of NMDA receptor
      subunits in the weaver mouse brain.
AB  - The weaver mutant mouse is characterized by degeneration of the dopaminergic
      mesencephalic neurons. The role of the dopaminergic system in the regulation of N
      methyl-d-aspartate (NMDA) receptor subunit expression was addressed in the
      present study. In situ hybridization experiments were conducted to determine the
      expression levels of the NMDA receptor subunit mRNAs, z1, epsilon1 and epsilon2,
      in striatum, nucleus accumbens, olfactory tubercle and cerebral cortical regions
      of 26-day-, 3- and 6-month-old weaver mice. Data indicated statistically
      significant increases in z1 and epsilon2 mRNA levels in 6-month-old weaver
      striatum, whereas at the same age epsilon1 mRNA expression was decreased in all
      striatal regions, as well as in the cortex. In the 26-day-old weaver striatum and
      nucleus accumbens, statistically significant increases were observed in epsilon1
      mRNA levels, whereas no changes were observed in the other two subunits. In the
      somatosensory cortex of 26-day-old weaver brain an increased expression of all
      three subunits was observed. The upregulation of NMDA receptor subunit expression
      observed in the somatosensory cortex can be attributed to a decreased activity of
      the glutamatergic thalamocortical pathway, following the degeneration of the
      nigrostriatal dopaminergic fibres. In the striatum, the present results
      demonstrate a differential control on the expression of z1 and epsilon2 subunits
      on the one hand, and epsilon1 subunit on the other. It is suggested that dopamine
      exerts a negative control on the expression of z1 and epsilon2 subunits, through
      a downregulation of transcription factors associated with the AP1 regulatory
      site, which is mediated by the activation of striatal dopamine D2 receptors.

PMID- 12786973
TI  - Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex
      and activation of apoptosis signal-regulating kinase 1 during seizure-induced
      neuronal death.
AB  - The consequences of activation of tumour necrosis factor receptor 1 (TNFR1)
      during neuronal injury remain controversial. The apoptosis signal-regulating
      kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase, can mediate
      cell death downstream of TNFR1. Presently, we examined the formation of the TNFR1
      signalling cascade and response of ASK1 during seizure-induced neuronal death.
      Brief (40 min) seizures were induced in rats by intra-amygdala microinjection of
      kainic acid, which elicited unilateral hippocampal CA3 neuronal death. Seizures
      caused a rapid decline in the expression of the silencer of death domains protein
      within injured CA3. Co-immunoprecipitation analysis revealed a commensurate
      assembly of a TNFR1 scaffold complex containing TNFR-associated death domain
      protein, receptor interacting protein and TNFR-activating factor 2. In addition,
      recruitment of TNFR-activating factor 2 was likely promoted by Bcl10-mediated
      sequestering of cellular inhibitor of apoptosis protein 2. Apoptosis signal
      regulating kinase 1 was sequestered in a complex that contained the molecular
      chaperone 14-3-3beta and protein phosphatase 5. Seizures triggered its
      dissociation, and the phosphorylation of the ASK1 substrates, mitogen-activated
      protein kinase kinase 3/6 and 4. Subsequently, protein phosphatase 5 translocated
      into the nuclei of degenerating CA3 neurons, while ASK1 colocalized with the
      adaptor proteins Daxx and TNFR-activating factor 2 at the outer membrane of
      injured CA3 neurons. Neutralizing antibodies to TNFalpha reduced the numbers of
      DNA damaged cells within the injured hippocampus. These data suggest ASK1 may be
      involved in the mechanism of seizure-induced neuronal death downstream of a TNFR1
      death-signalling complex.

PMID- 12786974
TI  - Reversible modulation of GABA(A) receptor-mediated currents by light is dependent
      on the redox state of the receptor.
AB  - Light has recently been shown to be a physical modulator of GABAA receptor
      activity. Here, we further characterize the effects of light on a native cortical
      and retinal population of GABAA receptors, and identify a possible mechanism for
      light induced potentiation using recombinant receptors. GABA-induced currents in
      cortical neurons were observed to be rapidly and reversibly potentiated following
      exposure to a brief flash of light (0.5-2 s; > 280 nm) directed via an optical
      fibre (50 micro m i.d.). GABAA receptor-mediated responses in retinal ganglion
      cells were also enhanced by light, while glycine-induced currents in these cells
      were unaffected by the same stimulus. We also determined that physiological
      levels of light, that is, those that would normally reach the retina, also
      enhanced GABA-induced currents. Finally, we observed that chemical reduction of
      recombinant alpha1beta2 and alpha1beta2gamma2S GABAA receptors by dithiothreitol
      substantially attenuated the effects of light. These results suggest that GABAA
      receptors can be reversibly modified by a brief pulse of light via an allosteric
      mechanism that is intimately linked to redox modulation.

PMID- 12786975
TI  - HCN channels are expressed differentially in retinal bipolar cells and
      concentrated at synaptic terminals.
AB  - Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels
      codetermine the integrative behaviour of neurons and shape their response to
      synaptic stimulation. We used immunohistochemistry and patch-clamp recording to
      study the composition and distribution of HCN channels in the rat retina. All
      four HCN channel isoforms (HCN1-4) are expressed differentially in the retina. In
      particular, different classes of bipolar cells have a different inventory of HCN
      channels. We found no evidence for the formation of heterooligomeric HCN
      channels. HCN channels are densely clustered at synaptic terminals of bipolar
      cells and photoreceptors. This suggests that HCN channels are involved in the
      control of transmitter release.

PMID- 12786976
TI  - Gene expression of neuropeptide Y in the nucleus of the solitary tract is
      activated in rats under restricted daily feeding but not under 48-h food
      deprivation.
AB  - The two neuropeptide Y (NPY) systems innervating the hypothalamic paraventrivular
      nucleus were examined regarding their roles in the prefeeding corticosterone peak
      developed under restricted daily feeding (RF). Protein and mRNA levels of NPY
      were measured in the arcuate nucleus (ARC) and the nucleus of the solitary tract
      (NST) in rats under 48-h food deprivation (48-hFD), RF, and 72-h food deprivation
      imposed after RF (post-RF 72-hFD) with 7 days of ad libitum feeding in between.
      NPY protein and mRNA levels in the ARC significantly increased with 48-hFD and
      decreased with re-feeding, whereas those in the NST were not changed by 48-hFD.
      When rats had RF imposed with free access to food from 10.00 to 12.00 h (lights
      on from 06.00 to 18.00 h) for 3 weeks, NPY concentrations in the ARC increased at
      10.00 h, just prior to the daily meal, but those in the NST did not change
      significantly throughout the period examined. On the other hand, NPY mRNA levels
      in both the ARC and NST increased before the meal supply and remained high for 4
      h after feeding. Under post-RF 72-hFD, the prefeeding peak of NPY mRNA was
      detected in the NST, but NPY mRNA levels in the ARC were continuously high
      throughout the 24-h period. These findings indicate that the NPY neurons from the
      NST are specifically activated by RF, whereas those from the ARC are generally
      stimulated by an increased food demand.

PMID- 12786977
TI  - Expression and functional role of mGluR3 and mGluR5 in human astrocytes and
      glioma cells: opposite regulation of glutamate transporter proteins.
AB  - We examined the regulation of glutamate transporter protein expression after
      stimulation with selective metabotropic glutamate receptor (mGluR) agonists in
      cultured human glial cells. mGluR3 and mGluR5 are expressed in human astrocytes
      and in human glioma cells in vivo as well as in vitro, as shown by either RT-PCR
      or western blot analysis. The selective group I agonist (S)-3,5
      dihydroxyphenylglycine produced a significant down-regulation of both GLAST and
      GLT-1 protein expression in astrocytes cultured in the presence of growth
      factors. This condition mimics the morphology of reactive glial cells in vivo
      including an increased expression of mGluR5 protein (observed in pathological
      conditions). In contrast, (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine, a
      selective agonist of group II metabotropic glutamate receptors, positively
      modulates the expression of GLAST and GLT-1 proteins. A similar opposite effect
      of (S)-3,5-dihydroxyphenylglycine and (2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine was observed for the expression of EAAT3 protein in
      U373 glioblastoma cell line. Selective group I and II antagonists prevented these
      effects. Pharmacological inhibition of mitogen-activated protein kinase and
      phosphatidylinositol-3-K pathways reduces the induction of GLT-1 observed in
      response to the group II metabotropic glutamate receptor agonist (2S,2'R,3'R)-2
      (2',3'-dicarboxycyclopropyl)glycine. Thus, mGluR3 and mGluR5 can critically and
      differentially modulate the expression of glutamate transporters and may
      represent interesting pharmacological targets to regulate the extracellular
      levels of glutamate in pathological conditions.

PMID- 12786978
TI  - Removal of PSA from NCAM affects the survival of magnocellular vasopressin- and
      oxytocin-producing neurons in organotypic cultures of the paraventricular
      nucleus.
AB  - The expression of the polysialic acid neural cell adhesion molecule (PSA-NCAM) in
      the hypothalamo-neurohypophyseal system has been correlated with morphofunctional
      plasticity. In this study, we investigated the role of PSA-NCAM in the survival
      of oxytocin (OT)- and vasopressin (VP)-producing magnocellular cells of this
      system. We used a recently developed organotypic slice culture model of the rat
      hypothalamic paraventricular nucleus (PVN) in which ciliary neurotrophic factor
      (CNTF) and leukemia inhibitory factor (LIF) are potent survival factors for
      magnocellular neurons. We demonstrate by means of confocal microscopy that
      cultured magnocellular VP and OT neurons express strong immunoreactivity for PSA
      NCAM. Removal of PSA from NCAM by the enzyme Endo N leads to a significant loss
      of both VP and OT neurons in the presence of low concentrations of CNTF. Endo N
      treatment did not change cell survival in the presence of LIF. These results
      suggest that, in addition to its role in neuro-glial plasticity, PSA-NCAM might
      also influence the trophic factor responsiveness of hypothalamic VP and OT
      neurosecretory cells.

PMID- 12786979
TI  - Pleiotrophin exhibits a trophic effect on survival of dopaminergic neurons in
      vitro.
AB  - To understand what kind of trophic factors are up-regulated in dopamine (DA)
      depleted striatum, we first analysed the up-regulation of mRNAs using a DNA
      microarray in DA-depleted striatum where DAergic inputs were denervated by 6
      OHDA. We then investigated whether or not such trophic factors had an effect on
      cultured dopaminergic neurons. The microarray analysis revealed that pleiotrophin
      (PTN), glial-derived neurotopic factor (GDNF) and others were up-regulated in DA
      depleted striatum. As PTN has been reported to have a wide range of trophic
      effects on neurons, we focused on the functional role of PTN in the present
      study. The increase in PTN mRNA was confirmed by Northern blotting at 1-3 weeks
      after the lesion, reaching a peak at 1 week. In embryonic day 15 mesencephalic
      neuron culture, PTN increased the number of tyrosine hydroxylase (TH) -positive
      neurons in a dose-dependent manner (125.2 +/- 2.0% of the control at 50 ng/mL),
      while a family protein, midkine (10 ng/mL) did not show any trophic effect (99.3
      +/- 0.7%). In addition, the PTN effect on DAergic neurons was additive to the
      GDNF effect. As PTN did not increase the number of microtubule-associated protein
      2 (MAP 2)-positive neurons or promote the proliferation of dopaminergic
      progenitors in a bromodeoxyuridine (BrdU) labelling study, the effect appeared to
      enhance the specific survival of dopaminergic neurons. Expression of PTN
      receptors (syndecan-3, PTP-zeta) was detected on the cultured mesencephalic
      neurons, and also up-regulated in DA-depleted striatum. The data indicate that
      PTN is up-regulated in DA-depleted striatum and exhibits a trophic effect
      specifically on the survival of cultured dopaminergic neurons.

PMID- 12786980
TI  - p53 inactivation leads to impaired motor synchronization in mice.
AB  - We have combined genetic and pharmacological approaches to investigate the
      behavioural consequences of inactivation of the murine p53 protein. Our
      behavioural analysis revealed that p53-null mice (p53KO) exhibit a very specific
      and significant motor deficit in rapid walking synchronization. This deficit,
      observed using the rotarod test, was the only behavioural defect of p53KO mice.
      We demonstrated that it was not due to an increase in neuronal number or abnormal
      connectivity in the olivo-cerebellar system, thought to control motor
      synchronization. In order to test the role of p53 in the central nervous system,
      we injected a pharmacological inhibitor of p53 activation, pifithrin-alpha, into
      the cerebellum of wild-type mice. This treatment mimicked the walking
      synchronization deficit of p53KO mice, suggesting that presence of p53 protein in
      the cerebellum is necessary to execute this synchronization of walking. Our
      investigation reveals a functional role of cerebellar p53 protein in adult
      walking synchronization.

PMID- 12786981
TI  - Synaptic changes characterize early behavioural signs in the ME7 model of murine
      prion disease.
AB  - Prion diseases are fatal, chronic neurodegenerative diseases of mammals,
      characterized by amyloid deposition, astrogliosis, microglial activation, tissue
      vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J
      mouse, we have shown previously that these animals display behavioural changes
      that indicate the onset of neuronal dysfunction. The current study examines the
      neuropathological correlates of these early behavioural changes. After injection
      of ME7-infected homogenate into the dorsal hippocampus, we found statistically
      significant impairment of burrowing, nesting and glucose consumption, and
      increased open field activity at 13 weeks. At this time, microglia activation and
      PrPSc deposition was visible selectively throughout the limbic system, including
      the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies,
      dorsal thalamus and, to a lesser degree, in regions of the brainstem. No increase
      in apoptosis or neuronal cell loss was detectable at this time, while in animals
      at 19 weeks postinjection there was 40% neuronal loss from CA1. There was a
      statistically significant reduction in synaptophysin staining in the stratum
      radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage
      to the dorsal hippocampus is known to disrupt burrowing and nesting behaviour. We
      have demonstrated a neuropathological correlate of an early behavioural deficit
      in prion disease and suggest that this should allow insights into the first steps
      of the neuropathogenesis of prion diseases.

PMID- 12786982
TI  - Effect of lidocaine and NMDA injections into the medial pontobulbar reticular
      formation on mastication evoked by cortical stimulation in anaesthetized rabbits.
AB  - Neurons of the dorsal nucleus reticularis pontis caudalis (nPontc) fire
      rhythmically during fictive mastication, while neurons of the ventral half tend
      to fire tonically (Westberg et al., 2001). This paper describes the changes in
      the pattern of rhythmical mastication elicited by stimulation of the sensorimotor
      cortex during inhibition or excitation of neurons in this nucleus and adjacent
      parts of nucleus reticularis gigantocellularis (Rgc) in the anaesthetized rabbit.
      Masticatory movements and electromyographic (EMG) activity of the masseter and
      digastric muscles produced by cortical stimulation were recorded before, during
      and after injections of a local anaesthetic (lidocaine) or excitatory amino acid
      N-methyl-d-aspartate (NMDA) into nPontc and Rgc through a microsyringe with
      attached microelectrode to record neuronal activity. Lidocaine inhibited local
      neurons and modified the motor program, and the effects varied with the site of
      injection. Most injections into the ventral half of nPontc increased cycle
      duration, digastric burst duration and burst area. The action of lidocaine in
      dorsal nPontc was more variable, although burst duration and area were often
      decreased. The effects on the muscle activity were always bilateral. Lidocaine
      block of the rostromedial part of Rgc had no effect on movements or on EMGs.
      Injections of NMDA excited local neurons and when injected into ventral nPontc,
      it completely blocked mastication. Dorsal injections either had no effect or
      increased cycle frequency, while decreasing burst duration and area. No increases
      in EMG burst duration or area were observed with NMDA. Our findings suggest that
      neurons of ventral nPontc tonically inhibit other parts of the central pattern
      generator during mastication, while dorsal neurons have mixed effects. We
      incorporated these findings into a new model of the masticatory central pattern
      generator.

PMID- 12786983
TI  - Neonatal administration of monosodium glutamate prevents the development of
      ethanol- but not psychostimulant-induced sensitization: a putative role of the
      arcuate nucleus.
AB  - Lesions of the arcuate nucleus by monosodium glutamate, goldthioglucose and
      oestradiol valerate treatments are known to prevent the acute stimulating effect
      of ethanol in mice. On the basis of these results, the current study analysed
      whether a lesion of the arcuate nucleus by monosodium glutamate was able to block
      ethanol-induced locomotor sensitization. To produce the arcuate nucleus lesions,
      pups were injected with saline or monosodium glutamate (4 mg/g body weight)
      subcutaneously on 5 alternate days, starting on postnatal day one. Sensitization
      treatments began 10 weeks after the initial lesions. Sensitization training
      consisted of six trials on alternate days, in which groups of mice were treated
      with ethanol (2 g/kg) or saline, and then tested in an open-field for the
      induction of locomotor activity. The present study demonstrated that animals with
      monosodium glutamate-induced lesions did not develop locomotor sensitization to
      ethanol. Different groups of mice were used to assay blood ethanol levels and to
      evaluate the effect of arcuate nucleus lesions on psychostimulant-induced
      locomotor sensitization. Sensitization to cocaine or amphetamine was spared in
      monosodium glutamate-pre-treated animals, although the lesion of arcuate nucleus
      reduced the sensitivity of mice to cocaine. Our findings therefore suggest that
      the arcuate nucleus may be critical for the neuroadaptations that underlie the
      behavioural sensitization to ethanol, in contrast to those mediating
      psychostimulant-induced sensitization.

PMID- 12786984
TI  - Influence of regular voluntary exercise on spontaneous and social stress-affected
      sleep in mice.
AB  - To investigate the impact of regular physical exercise on sleep, we assessed
      sleep-wake behaviour in male C57BL/6N mice with and without long-term access
      (i.e. 4 weeks) to a running wheel. We studied sleep-wake behaviour during
      undisturbed conditions as well as after social stress. The exercising mice ran
      approximately 4 km/day, which affected their physical constitution, their
      spontaneous sleep-wake pattern and their endocrine and sleep responses to stress.
      When compared with the control mice, exercising animals had more muscle
      substance, less body fat and heavier adrenal glands. At baseline, exercising mice
      showed fewer, but longer-lasting, sleep episodes (indicating improved sleep
      consolidation) and less rapid-eye-movement sleep. In both control and exercising
      mice, mild social stress (elicited by a 15-min social conflict) evoked elevated
      plasma levels of adrenocorticotrophic hormone and corticosterone, an increase in
      non-rapid-eye-movement sleep, an enhancement of low-frequency activity in the
      electroencephalogram within non-rapid-eye-movement sleep (indicating increased
      sleep intensity) and a decrease in wakefulness. However, as compared with the
      control animals, exercising mice responded to social stress with higher
      corticosterone levels, but not adrenocorticotrophic hormone levels, suggesting an
      increased sensitivity of their adrenal glands to adrenocorticotrophic hormone.
      Moreover, in control mice, social stress increased rapid-eye-movement sleep in
      parallel to non-rapid-eye-movement sleep, whereas this stressor selectively
      decreased rapid-eye-movement sleep in exercising animals. Corticosterone is known
      to decrease rapid-eye-movement sleep. Therefore, changes in the regulation of the
      hypothalamic-pituitary-adrenocortical axis as a result of the long-term exercise
      may contribute to the observed differences in spontaneous and social stress
      affected sleep. In conclusion, regular exercise appears to increase sleep quality
      and reverses the effects of mild social stress on rapid-eye-movement sleep.

PMID- 12786985
TI  - Cocaine-induced psychomotor activity is associated with its ability to induce c
      fos mRNA expression in the subthalamic nucleus: effects of dose and repeated
      treatment.
AB  - Factors that modulate the psychomotor activating effects of amphetamine and
      cocaine, such as environmental novelty and dose, also regulate the ability of
      these drugs to induce c-fos mRNA expression in the subthalamic nucleus (STN). We
      hypothesized therefore that engagement of the STN may be important for stimulant
      induced psychomotor activation. To further test this hypothesis we examined
      whether repeated treatment with cocaine, which enhances its psychomotor
      activating effects (i.e. produces behavioural sensitization), also enhances its
      ability to induce c-fos expression in the STN. In addition, given that STN
      activity is thought to be influenced by preproenkephalin mRNA-containing (ENK+)
      neurons in the caudate-putamen, we also examined whether repeated cocaine
      treatment alters c-fos expression in ENK+ cells. We report that: (i) cocaine
      pretreatment enhances the ability of a cocaine challenge to induce c-fos mRNA
      expression in the STN, and this effect is most robust at challenge doses where
      behavioural sensitization is observed; (ii) the ability of cocaine to induce c
      fos in the STN is independent of the ability of cocaine to engage ENK+ cells.
      These results support the idea that the STN is involved in stimulant-induced
      psychomotor activation and sensitization, but suggest that stimulant-induced
      engagement of the STN is not dependent on ENK+ cells in the caudate-putamen.
      These findings may have implications concerning the neurobiological mechanisms
      underlying the behavioural effects of psychostimulant drugs.

PMID- 12786986
TI  - Glutamate motivational ensembles in nucleus accumbens: rostrocaudal shell
      gradients of fear and feeding.
AB  - This study demonstrates that microinjection of an AMPA/kainate glutamate
      antagonist elicits motivated fear and feeding behaviour mapped along rostrocaudal
      gradients of positive-to-negative valence in nucleus accumbens shell (similar to
      rostrocaudal shell gradients recently reported for GABA agonist microinjections).
      Rats received rostral or caudal microinjections of the glutamate AMPA/kainate
      receptor antagonist DNQX (0, 50, 450 or 850 ng in 0.5 micro L) or the NMDA
      receptor antagonist MK-801 (0, 0.5, 1 or 2 micro g in 0.5 micro L), into medial
      accumbens shell prior to behavioural tests for fear, feeding or conditioning of
      place preference or avoidance. Another group received rostral or caudal
      microinjections of DNQX in nucleus accumbens core. Rostral shell DNQX
      microinjections potently increased appetitive food intake and established only
      weak conditioned place avoidance. Caudal shell DNQX microinjections elicited
      defensive treading behaviour, caused rats to defensively bite the experimenter
      and emit fearful distress vocalizations when handled, and established strong
      conditioned place avoidance. By contrast, no rostrocaudal gradients of
      motivational bivalence were produced by microinjections of the glutamate
      AMPA/kainate receptor antagonist DNQX into the core, or by microinjections of the
      NMDA antagonist MK-801 into the shell. Our results indicate that appetitive and
      aversive motivation is carried in anatomically differentiated channels by
      mesocorticolimbic glutamate signals to microcircuits in the medial shell.
      Hyperpolarization of local shell ensembles by AMPA/kainate glutamate receptor
      blockade elicits fear and feeding behaviours mapped along distinct positive-to
      negative rostrocaudal gradients.

PMID- 12786987
TI  - Characterization of the human visual V6 complex by functional magnetic resonance
      imaging.
AB  - Magnetoencephalography of a visual area along the human parieto-occipital sulcus
      suggested that this region represents the human homologue of the monkey visual
      area V6 complex (visual area V6/visuomotor area V6A) involved in the integration
      of visual and somatomotor information. We used functional magnetic resonance
      imaging at 2.0 T and 2 x 2 x 3 mm3 resolution (16 sections) to characterize
      visual areas along the parieto-occipital sulcus in five healthy human subjects.
      Paradigms comprised a full-field checkerboard stimulation, a full-field luminance
      flicker as well as a foveal and peripheral luminance flicker using both a direct
      and differential design for comparing functional states. Along the parieto
      occipital sulcus, and in contrast to primary visual areas, luminance stimulation
      evoked much larger activation volumes than checkerboard stimulation. Moreover,
      based on anatomic landmarks, luminance stimulation identified two functionally
      distinct regions of parieto-occipital sulcus activations: an inferior part
      (supposedly visual area V6) and a superior portion (supposedly visuomotor area
      V6A). With these assignments, foveal vs. peripheral luminance stimulation
      revealed a weaker foveal overrepresentation in visual area V6/visuomotor area V6A
      than in early visual areas, and only a mild tendency for a retinotopic
      organization in visual area V6. Further analyses of the functional coding of the
      human visual area V6 complex require functional magnetic resonance imaging at
      even higher spatial resolution.

PMID- 12786988
TI  - Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine
      self-administration.
AB  - Several human and rat studies suggest that the striatal dynorphin system is
      important for neuroadaptation following cocaine exposure. In the current study,
      prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and
      chronic phases of cocaine self-administration. Adult Rhesus monkeys were trained
      to self-administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg
      per injection) on a fixed interval 3-min schedule for 5 or 100 sessions. Each
      session ended after 30 reinforcers were delivered. The PDYN mRNA expression was
      analysed in the precommissural striatum using in situ hybridization
      histochemistry. We found a specific activation of PDYN mRNA expression in the
      limbic-innervated patch/striosome compartment of the dorsal caudate and dorsal
      putamen during the initial (i.e. 5 day) phase of the high dose cocaine self
      administration. After 100 days of the high dose exposure, the patch/striosome
      compartment remained activated, but an increase in PDYN mRNA levels was also
      evident in the sensorimotor-connected matrix compartment of the caudate. Neither
      self-administration phase resulted in significant changes in the corresponding
      striatal regions of the low dose cocaine-exposed primates. Moreover, cocaine self
      administration failed to alter the PDYN mRNA expression in high- or low
      expressing PDYN cell populations in the nucleus accumbens during any condition
      studied. These results demonstrate the vulnerability of the dorsal striatum (in
      particular the caudate) to neuroadaptations following long-term high dose cocaine
      self-administration. In addition, the temporal nature of the changes in PDYN gene
      expression within the striatal compartments could reflect a change in drug
      responsivity that occurs during the transition to drug dependence.

PMID- 12786989
TI  - Individual differences in prefrontal cortical activation on the Tower of London
      planning task: implication for effortful processing.
AB  - Solving challenging ('effortful') problems is known to involve the dorsal and
      dorsolateral prefrontal cortex in normal volunteers, although there is
      considerable individual variation. In this functional magnetic resonance imaging
      study, we show that healthy subjects with different levels of performance in the
      Tower of London planning task exhibit different patterns of brain activation. All
      subjects exhibited significant bilateral activation in the dorsolateral
      prefrontal cortex, the anterior and posterior cingulate areas and the parietal
      cortex. However, 'standard performers' (performance < 70% correct) and 'superior
      performers' (performance >70% correct) differed in the patterns of activation
      exhibited. Superior performers showed a significantly more spatially extended
      activation in the left dorsolateral prefrontal cortex than did standard
      performers, whereas the latter group tended to show increased activation of the
      anterior cingulate region.

PMID- 12786990
TI  - Diazepam-induced changes on sleep and the EEG spectrum in mice: role of the
      alpha3-GABA(A) receptor subtype.
AB  - Benzodiazepines reduce EEG slow-wave activity in non-REM sleep by potentiating
      GABAergic neurotransmission at GABAA receptors via a modulatory binding site.
      However, the mechanisms of action underlying the effects of benzodiazepines on
      sleep and the sleep EEG are still unknown. Slow waves during sleep are generated
      by the corticothalamic system and synchronized by the inhibitory GABAergic
      neurons of the reticular thalamic nucleus. This region contains exclusively
      alpha3-containing GABAA receptors. We investigated the role of these receptors in
      the mediation of diazepam effects on the sleep EEG by studying point-mutated mice
      in which the alpha3-GABAA receptor is diazepam-insensitive [alpha3(H126R)]. Sleep
      was recorded for 12 h after i.p. injection of 3 mg/kg diazepam or vehicle at
      light onset in alpha3(H126R) and wild-type controls (n = 13-17 per genotype). The
      main effect was a marked reduction of slow-wave activity (EEG power density in
      0.75-4.00 Hz) in non-REM sleep and a concomitant increase in frequencies above
      15.00 Hz in non-REM sleep and waking in both genotypes. Neither effect of
      diazepam differed significantly between the genotypes. Despite the exclusive
      expression of alpha3-containing GABAA receptors in the reticular thalamic
      nucleus, these receptors do not seem to be critical for the mediation of the
      effects of diazepam on the sleep EEG.

PMID- 12786991
TI  - Stress-mediated heart rate dynamics after deletion of the gene encoding
      corticotropin-releasing factor receptor 2.
AB  - The objective of the present study was to investigate the potential role of
      corticotropin-releasing factor receptor subtype 2 (CRFR2) in autonomic regulation
      of heart rate and heart rate variability under physiological conditions in
      conscious mice. Heart rate dynamics during novelty exposure and auditory fear
      conditioning were assessed by radiotelemetry. Heart rate responses and heart rate
      variability values were not different in CRFR2+/+ and CRFR2-/- mice during
      novelty exposure, which was associated with similar locomotor activity exhibited
      by both genotypes. The heart rate responses during retention of conditioned
      auditory fear were similar and the exponential relationship between heart rate
      and heart rate variability was independent of genotype. Pharmacological
      stimulation of the peripheral CRFR2beta by intraperitoneal injection of 200 ng
      human/rat corticotropin-releasing factor yielded a sustained tachycardia in
      wildtype control (CRFR2+/+) mice which was absent in CRFR2-deficient (CRFR2-/-)
      mice. Similarly, the tachycardia was effectively blocked by preinjection of the
      CRFR2 antagonist antisauvagine-30. In conclusion, the results indicate the
      involvement of CRFR2 in heart rate dynamics upon pharmacological stimulation but
      demonstrate that CRFR2 is not involved in baseline heart rate regulation and
      stress-mediated modulation of heart rate responses.

PMID- 12786992
TI  - Natural killer receptor repertoires in transplantation.
AB  - Natural killer (NK) lymphocytes are potent effector cells that are controlled by
      the expression of a variety of cell surface receptors with either inhibitory or
      activating functions. The genetic and functional diversity of this receptor
      repertoire and the role of HLA class I molecules as a major group of NK receptor
      ligands create an innate alloreactive capacity in this cell type. Both animal
      models and in vitro studies have implicated NK cells as contributors to the
      pathology of clinical transplantation. However, recent clinical studies have
      indicated the potential benefit of exploiting NK cell alloreactivity in
      mismatched haematopoietic stem cell transplantation. Further investigations of NK
      cell alloreactivity will undoubtedly reveal additional applications of this
      fundamental cell type in clinical transplantation.

PMID- 12786993
TI  - Tumour immunology, vaccination and escape strategies.
AB  - Our increasing knowledge of the mechanisms by which tumour cells escape immune
      effector cells is helping to establish new approaches to therapeutic vaccination
      against tumour development. One of the escape mechanisms used by tumour cells is
      the generation of multiple variants with different HLA phenotypes. These MHC
      class I phenotypic alterations play a key role in the tumour-host scenario, as
      they are crucial molecules for antigen presentation to T cells and modulation of
      natural killer (NK) cell activity. This review presents evidence indicating that
      tumours develop sophisticated MHC phenotypes that allow them to escape immune
      surveillance. We evaluate the importance of these alterations in terms of the
      potential development of therapeutic approaches to immune vaccination.

PMID- 12786994
TI  - Recognition of HLA-A*0248 in a Chinese donor.
AB  - HLA-A*0248, a rare allele originally found in an individual of Filipino
      background, was detected in a Chinese donor. We confirmed the novel sequence and
      analysed its serological reaction pattern. The exon 2 sequence of A*0248 was
      apparently generated in a gene conversion event with an A2 gene, receiving a
      sequence segment comprising codons 56 to 74 from an A*24 donor gene. Serological
      typing showed a clear-cut A2 reaction pattern, indicating that the three amino
      acid positions 62, 65 and 74, are probably not a critical part of the A2 epitope.
      Our typing experience also demonstrated that different typing technologies often
      complement each other in fine HLA typing.

PMID- 12786995
TI  - Genetic variation in the IGSF6 gene and lack of association with inflammatory
      bowel disease.
AB  - The immunoglobulin superfamily 6 gene (IGSF6) on chromosome 16p11-p12 has been
      investigated as a positional and functional candidate for inflammatory bowel
      disease (IBD) susceptibility. Screening of the six exons of IGSF6 for single
      nucleotide polymorphisms (SNPs) detected four novel SNPs, and validated three of
      six SNPs listed in the international SNP database (dbSNP). The seven SNPs in
      IGSF6 formed five distinct linkage disequilibrium groups. There was no evidence
      for association of the common SNPs with disease in a large cohort of patients
      with IBD. The novel SNPs and the linkage disequilibrium map will be a useful
      resource for the analysis of IGSF6 in other immune disorders.

PMID- 12786996
TI  - A new allelic variation within the 5'-flanking region of the interleukin-10 gene.
AB  - At -2471 bp from the transcriptional start site of the interleukin-10 (IL-10)
      gene, the inverted repeat TG/CA was previously identified and designated IL
      10.IR. In an analysis of samples from 200 Germans (Caucasian) and 286 Gabonese
      (Central African), three different alleles, IL-10.IR6, IL-10.IR7 and IL-10.IR8,
      were identified. In the Caucasians, IL-10.IR6 and IL-10.IR8 were found only once,
      in each case with IL-10.IR7 as the corresponding second allele.

PMID- 12786997
TI  - Lack of association between transporter associated with antigen processing (TAP)
      and HLA-DM gene polymorphisms and antibody levels following measles vaccination.
AB  - The transporter associated with antigen processing (TAP) and human leukocyte
      antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both
      HLA class I and class II-restricted antigen presentation. We hypothesized that
      polymorphisms within the TAP and DM genes may influence antibody levels following
      measles vaccination. We examined TAP and DM polymorphisms in 242 school children
      from Olmsted County, Minnesota, USA who received one dose of measles-mumps
      rubella-II (MMR-II) vaccine at the age of 15 months. Based on the level of serum
      measles-specific immunoglobulin G (IgG) antibodies, subjects were classified as
      seronegatives (n = 72) or seropositives (n = 170). We determined TAP1 and TAP2
      allele types by polymerase chain reaction (PCR) amplification of specific alleles
      (PASA) and determined DM allele type by PCR amplification followed by direct
      sequencing of the polymorphic sites. We analysed the data for any TAP or DM
      allelic association with antibody levels post measles vaccination using the chi
      square test and univariate linear regression analysis. We found no trend in the
      overall distribution of TAP and DM genotype frequencies between seronegative and
      seropositive subjects, suggesting that TAP and DM polymorphism and antibody
      levels following measles vaccination are not directly associated. In addition, we
      did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM
      (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine
      in this study group. Our study suggests that TAP and DM gene polymorphisms do not
      influence antibody levels post measles vaccination.

PMID- 12786998
TI  - Association of ABO histo-blood group B allele with myocardial infarction.
AB  - To investigate a possible association of ABO blood group alleles with myocardial
      infarction, a case-control study comprising 177 patients (median age 57.0 years;
      range 32-72 years) and 89 controls was performed. The distributions of the ABO
      blood-genotype O1, O2, A1, A2 and B alleles were assessed by analysis of genomic
      DNA, using the sequence-specific primer-polymerase chain reaction (PCR-SSP)
      technique to investigate exons VI and VII on chromosome 9. The prevalence of the
      B allele was 2.5 times higher amongst patients with a history of myocardial
      infarction than amongst controls (16.3 vs. 6.7%; P = 0.034, Fisher's exact test).
      There was an association between patients carrying the B allele and myocardial
      infarction, with an odds ratio (OR) of 2.7 (95% confidence interval 1.1-6.8). The
      B allele remained an independent risk factor for myocardial infarction (P =
      0.038) when classical risk factors were adjusted for by unconditional logistic
      regression. In conclusion, the ABO blood group B allele was found to be an
      independent risk factor for myocardial infarction.

PMID- 12786999
TI  - Comparison of TAP2 frequencies in type 1 diabetes patients and healthy controls
      from three ethnic groups indicates an African origin for the TAP2 G allele.
AB  - In order to determine the ethnic origin of the transporter associated with
      antigen processing 2 (TAP2) G allele, initially discovered by us in a group of
      type 1 diabetes (insulin-dependent diabetes mellitus) patients living on Reunion
      Island, HLA TAP2 typing was performed using the polymerase chain reaction
      amplification refractory mutation system (PCR-ARMS) method in type 1 diabetes
      patients and unrelated healthy controls of three different ethnic groups
      (Caucasians, Indians and black Africans from Senegal and Mauritius). The
      comparison of TAP2 allele frequencies in controls showed significant racial
      (ethnic) differences. The TAP2*0101 and TAP2 C alleles were increased,
      respectively, in the Caucasian (50% in Caucasians vs. 40% in other groups) and
      Senegalese (27% in Senegalese vs. 10% in other groups) populations. In comparison
      with Caucasians, the TAP2*0201 variant was significantly increased in the Indian
      population and decreased in the Senegalese black population. In addition, the
      TAP2 G allele was observed in the two African populations studied but not in the
      Caucasian or Indian population. This observation is consistent with the view that
      this allele is restricted to populations of African origin. In addition, we have
      determined the large extended haplotype DQA1-DQB1-DRB1 associated with TAP2 G. We
      found that this allele is preferentially associated with the large conserved
      haplotype HLA DQA1*0501-DQB1*0201-DRB1*0301.

PMID- 12787000
TI  - The distribution of 13 killer-cell immunoglobulin-like receptor loci in UK blood
      donors from three ethnic groups.
AB  - Killer-cell immunoglobulin-like receptors (KIRs) can inhibit the killing activity
      of natural killer (NK) cells if they interact with their ligand, class I HLA.
      Using a modified polymerase chain reaction-sequence-specific primers (PCR-SSP)
      method for typing KIRs using genomic DNA, we compared KIR frequencies in three
      ethnic populations drawn from UK blood donors. We found a significantly lower
      frequency of the inhibitory KIRs KIR2DS1 and 3DS1 in Afro-Caribbean blood donors.
      Despite this, there was a (non-significant) increase in the B haplotype in Afro
      Caribbean and Indian Asian donors. Some donors from each group tested negative
      for all non-inhibitory KIRs. In addition, we describe several new KIR profiles.
      Analysis of linkage disequilibrium was consistent with previously published
      findings.

PMID- 12787001
TI  - The HLA-DRB, -DQB polymorphism and anti-insulin antibody response in Slovenian
      patients with type 1 diabetes.
AB  - A combination of specific HLA class II antigens and the presence of type 1
      diabetes (T1D)-related antibodies has a high positive predictive value for T1D
      but low sensitivity. The aim of the present study was to determine the
      frequencies of HLA-DRB-DQB deduced haplotypes associated with susceptibility and
      protection in Slovenian patients with established T1D, to evaluate the
      relationship between the HLA-DRB1-QBP-DQB1 haplotypes and the presence of insulin
      autoantibodies (IAA) and glutamic acid decarboxylase antibodies (GADA), and to
      access the possible impact of polymorphic QBP promoters on this relationship. A
      cohort of 135 patients with T1D (age 17.5 +/- 7.0 years, duration of T1D 9.14 +/-
      6.3 years) was investigated. HLA-DRB1 and DQB1 alleles were typed using the
      polymerase chain reaction (PCR)-reverse line blot method. QBP promoter region
      alleles were determined using PCR-sequence-specific oligonucleotide hybridization
      (SSO) and PCR-sequence-specific primers (SSP). IAA and GADA antibodies were
      determined by enzyme-linked immunosorbent assay (ELISA). The chi-square test with
      Yates' correction was used for statistical analysis. Deduced haplotypes DRB1*0301
      DQB1*0201 (P = 0.0001, OR = 3.4), DRB1*0401-DQB1*0302 (P = 0.0001, OR = 29.8),
      and DRB1*0402-DQB1*0302 (P = 0.008, OR = 4.7) were significantly more common, and
      DRB1*1501-DQB1*0602 (P = 0.0001, OR = 0.03) significantly less common in the
      investigated cohort than in a Slovenian control group. The highest risk and the
      strongest protective HLA-DR-DQ haplotypes found in Slovenian patients with T1D
      did not differ from those found in other Caucasian populations. While the
      DRB1*0301-QBP2.1-DQB1*0201 haplotype, where QBP2.1 did not help to further
      distinguish DQB1*0201-possessing haplotypes in IAA-positive and IAA-negative
      patients, was strongly associated with the presence of IAA, the DRB1*0101-QBP5.12
      DQB1*0501 haplotype, although not protective compared to the control population,
      was associated with an absence of IAA in the investigated cohort. It is suggested
      that there may be a combined influence of the QBP5.12 promoter and the DQB1*0501
      functional molecule on reduced IAA production.

PMID- 12787002
TI  - Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002.

PMID- 12787003
TI  - Nomenclature for factors of the HLA system, update January 2003.

PMID- 12787004
TI  - Nomenclature for factors of the HLA system, update February 2003.

PMID- 12787005
TI  - Nomenclature for factors of the HLA system, update March 2003.

PMID- 12787006
TI  - Detection and treatment of depression in pallitative care patients.

PMID- 12787008
TI  - Why patients don't take part in cancer clinical trials: an overview of the
      literature.
AB  - Clinical trials have been recognized extensively within the literature as a
      crucial component in the research, development and evaluation of treatment
      strategies within health care services. However, it has also been acknowledged
      that clinicians and researchers have historically experienced problems in terms
      of attaining adequate recruitment to clinical trials. The purpose of this review
      is to explore some of these questions and, more importantly, provide possible
      explanations for non-participation in clinical trials, with specific reference to
      the field of cancer research. In addition, approaches that have been used by
      researchers in order to explore the issue of non-participation, and suggestions
      in terms of the ways that further research into this key area may be undertaken,
      are also be considered.

PMID- 12787009
TI  - Using simulated patients in a multiprofessional communications skills programme:
      reflections from the programme facilitators.
AB  - This paper discusses a multiprofessional, 4-day communication skills programme in
      which participants explore the challenges of communicating with cancer patients
      and their families. Effective communication and skilled emotional support are
      essential prerequisites for high quality care in oncology and palliative care
      settings. This aspect of care presents major challenges to nurses and other
      health care professionals. It is acknowledged that health professionals often
      lack the requisite skills to communicate meaningfully with this patient group and
      that tangible benefits accrue from training in this area. Using simulated
      patients, structured feedback and small group discussions, this multiprofessional
      programme seeks to provide a forum that enables participants to acquire
      confidence and competence in a safe, comfortable and non-threatening environment.
      The programme structure presents several challenges in terms of providing a
      learning experience that addresses the diverse educational of a heterogeneous
      learning group. Participants' comments and programme facilitators reflections
      suggest that the programme is successful in addressing these challenges and
      providing a meaningful learning experience.

PMID- 12787010
TI  - Sustaining the cocoon: the emotional inoculation produced by complementary
      therapies in palliative care.
AB  - The aim of this study is to explore, from a medical sociological perspective, the
      use of complementary therapies by palliative care nurses. This paper shows how
      the conceptual vocabulary developed by Giddens [Giddens A. (1990) The
      Consequences of Modernity. Polity Press, Cambridge; Giddens A. (1991) Modernity
      and Self-Identity. Polity Press, Cambridge] relating to trust, ontological
      security, existential anxiety and the importance of protective cocoons,
      facilitates understanding of the use of complementary therapies in palliative
      care. This is a qualitative study based on semi-structured interviews. During
      analysis both thematic content and narrative form of the interviews are
      scrutinized. Analysis shows that the concepts Giddens developed enable the use of
      complementary therapies to be seen in new ways. In particular, they facilitate
      the application of a complementary therapy being seen as an emotional
      inoculation. Similar to the emotional inoculation Giddens speaks about, an infant
      receiving from its caretaker in childhood which enables a child to have a
      protective cocoon which it carries round with it throughout life and can draw on
      when faced with difficulties, the application of a complementary therapy in
      palliative care can be seen in terms of a booster injection being received by an
      adult, from their professional caretaker, in time of particular need. This
      injection sustains a person's protective cocoon at a time of vulnerability.

PMID- 12787011
TI  - Hypnotherapy and cognitive-behaviour therapy in cancer care: the patients' view.
AB  - Psychological intervention is not widely available for emotionally distressed
      patients with cancer. The purpose of this study is to investigate and report on
      the experiences of eight patients who participated in a programme consisting of
      hypnotherapy and cognitive-behaviour therapy. Following the 12-session
      intervention, qualitative analysis of interview data demonstrated that patients
      had acquired the skills to enable them to cope, both with invasive medical
      procedures and the psychological traumas they faced. The findings also indicated
      some initial misconceptions about hypnotherapy and the need to provide a therapy
      setting sensitive to the needs of cancer patients undergoing active medical
      treatment.

PMID- 12787012
TI  - Building a model to determine the cost-effectiveness of breast cancer screening
      in France.
AB  - This paper describes the methods and initial validation of a cost-effectiveness
      model developed to simulate the breast cancer screening situation in France. The
      first screening pilot programmes were set up in France in 1989 to test the
      feasibility of a decentralized screening model based in a large number of
      existing non-dedicated radiology centres. The present cost-effectiveness model
      was built as a tool to help guide current policy discussions on the future of
      screening in France. This Markov model compares the costs and effects expected
      when a screening programme is offered to a given cohort of women to those
      expected in the absence of screening. The model was initially validated using
      current results from the Bas-Rhin screening programme and local cancer registry
      epidemiological data. Over a 20-year period, 315 274 women would attend for
      screening, of whom 12 491 would be recalled for further assessment. 4423 cancers
      would be detected, resulting in 637 deaths. Screening allows the detection of 106
      additional cancer cases, thereby preventing 92 deaths, and saves 1522 life-years
      compared with a situation without screening. Breast cancer mortality is reduced
      by 12.6%, yielding a cost-effectiveness ratio of 137 000 FF per life-year saved.
      The results of initial analyses suggest that the model is capable of suitably
      assessing the impact of breast cancer screening in terms of costs and effects.
      Further scenario analyses are needed to understand the impact of screening policy
      changes on the costs and effectiveness of future screening programmes.

PMID- 12787013
TI  - The effectiveness of scalp cooling in preventing alopecia for patients receiving
      epirubicin and docetaxel.
AB  - The aim of this study was to establish the effectiveness of scalp cooling in
      preventing alopecia for patients with breast cancer who received the trial
      combination chemotherapy of Epirubicin and Docetaxel. Doubt remains about the
      general effectiveness of scalp cooling in preventing hair loss for patients
      receiving chemotherapy. There is very little information available about its
      specific effectiveness with combinations of Taxanes and Anthracycline drugs. Of
      the 40 patients who received this drug combination, 10 were included in a pilot
      study whereas the remaining 30 constituted the main study sample. A randomized
      controlled study was undertaken whereby the intervention group received scalp
      cooling via gel cool caps and the control group received no specific preventative
      intervention. Nurses assessed participants' hair loss using a modified version of
      the WHO scale at seven time points and also recorded hair loss photographically.
      Two independent experts rated the photographs using the same scale. Patients self
      reported in relation to overall hair loss, hair condition, levels of emotional
      upset, negativity about appearance, hair re-growth and wig use. Significantly
      greater hair loss was apparent in the control group during most of the treatment
      period. However, the level of protection afforded by the cool caps was relatively
      poor with this chemotherapy combination. The marginal benefits of scalp cooling
      in this context must be clearly explained to patients.

PMID- 12787014
TI  - Pruritus: scratching the surface.
AB  - Patients who are jaundiced have an accumulation of bile acids in the plasma,
      which can cause intense irritation. Pruritus associated with cholestasis is a
      difficult problem; the pathogenesis remains unknown. In severe cases, it can lead
      to sleep deprivation and contribute to significant psychological disturbances.
      Patients who have pancreatic cancer with unrelieved jaundice often say the
      itching is the worst symptom. Typically patients are prescribed Chlorpheniramine,
      an antihistamine, and Choleystiramine, which binds bile salts in the bowel and
      helps to facilitate their excretion. Choleystiramine only works if biliary
      obstruction is incomplete; it is not very palatable and can cause diarrhoea. A
      review of the literature revealed that certain drugs not intended for the
      treatment of pruritus associated with malignant cholestasis eased the symptoms
      considerably. There was very little relating to skin care in the majority of
      articles dealing with pruritus. Twycross (1997, Introducing Palliative Care, pp.
      112-114) stated that most patients with advanced cancer and pruritus may never
      need an antihistamine if given appropriate skin care and that drugs are of little
      use in isolation. A regime of skin care was devised with the main aim of keeping
      the skin moist and cool. Factors were identified that would alleviate or
      aggravate the skin surface. With prompt treatment, symptoms were reduced and in
      some cases eradicated completely. The information gained has led to the planning
      of a trial to determine efficacy of skin care management and different drug
      therapies to relieve debilitating pruritus when established treatments fail. Key
      points include: (1) treatment of pruritus associated with malignant disease is
      directed towards effective management of the underlying cause; (2) given the
      subjective nature of pruritus, it is poorly understood and management presents a
      challenging problem; and (3) effective skin management can help to alleviate
      debilitating symptoms. Certain drugs not intended for treatment of pruritus
      associated with malignant cholestasis have proven to be effective.

PMID- 12787015
TI  - Do bowel cancer patients participate in treatment decision-making? Findings from
      a qualitative study.
AB  - The views of bowel cancer patients towards treatment decision-making and the
      extent to which they participate in this process were investigated. A prospective
      longitudinal qualitative study was conducted based on 55 new consultations
      between oncologists and bowel cancer patients and interviews with 37 recently
      diagnosed patients, 28 of whom were re-interviewed after 6 months. The interview
      and consultation data were transcribed verbatim and coded. Theoretical
      comparisons were made between the interviews and themes emerging from the
      consultation narratives. The analysis revealed that most bowel cancer patients
      preferred a limited role in the treatment decision-making process, preferring to
      delegate the responsibility to the clinician. However, they did not always
      consider themselves as 'passive' participants within the consultation and many
      felt that they had made the final decision to accept or refuse treatment. The
      consultation data shows that when a treatment recommendation was not forthcoming
      from the oncologist, patients became more proactive in the consultation, often
      taking the initiative to participate. It is concluded that patients who indicate
      a desire to participate in these types of consultations should be encouraged to
      do so and oncologists should try to identify those patients who could benefit
      from a greater role in treatment decision-making.

PMID- 12787016
TI  - Care and the older person with cancer.
AB  - Care of older people with cancer has received relatively little attention in the
      literature and this area of caring practice has yet to be firmly established in
      professional discourse. References to the increasing proportion of older people
      in the population are common, as are references to the problems associated with
      old age, whether these are seen as medical, or as inevitable consequences of
      natural processes. Health care for older people has sometimes been reported to be
      routinized or basic, and as taking little account of individual perspectives, and
      the 'discourse of senescence' represents a tendency to understand old age and the
      aged body in terms of degeneration and deterioration. Here, it is argued that
      older people are often portrayed as separate and diminished, and have little
      control over the definition of themselves as users of health services. This
      represents a constraint upon the possibilities of caring practice. Divesting
      ourselves of the 'discourse of senescence' may be a fundamental part of
      developing caring practice for older people with cancer in the future.

PMID- 12787017
TI  - The experience of dysphagia and its effect on the quality of life of patients
      with oesophageal cancer.
AB  - This qualitative study was designed to explore the experience of dysphagia in
      oesophageal cancer and how this impacts on quality of life. The aim of the study
      was to add to the knowledge and comprehension of this poorly understood symptom.
      Data was collected through in-depth interview and administration of the EORTC QLQ
      C30 and EORTC QLQ-OES24 quality of life tools with six people with incurable
      oesophageal cancer who had dysphagia. The interviews were tape-recorded and then
      transcribed verbatim for each participant. Through a thematic analysis of the
      interview data and a descriptive analysis of the questionnaires a detailed
      description of the experience of dysphagia and its impact on quality of life was
      obtained. Five basic themes emerged from the participant's accounts and these
      were recognizing dysphagia, the physical experience, the emotions evoked, the
      impact on social life and dysphagia and treatment. In conclusion dysphagia is a
      troublesome symptom which affects all aspects of quality of life.

PMID- 12787020
TI  - On peptide bond formation, translocation, nascent protein progression and the
      regulatory properties of ribosomes. Derived on 20 October 2002 at the 28th FEBS
      Meeting in Istanbul.
AB  - High-resolution crystal structures of large ribosomal subunits from Deinococcus
      radiodurans complexed with tRNA-mimics indicate that precise substrate
      positioning, mandatory for efficient protein biosynthesis with no further
      conformational rearrangements, is governed by remote interactions of the tRNA
      helical features. Based on the peptidyl transferase center (PTC) architecture, on
      the placement of tRNA mimics, and on the existence of a two-fold related region
      consisting of about 180 nucleotides of the 23S RNA, we proposed a unified
      mechanism integrating peptide bond formation, A-to-P site translocation, and the
      entrance of the nascent protein into its exit tunnel. This mechanism implies
      sovereign, albeit correlated, motions of the tRNA termini and includes a spiral
      rotation of the A-site tRNA-3' end around a local two-fold rotation axis,
      identified within the PTC. PTC features, ensuring the precise orientation
      required for the A-site nucleophilic attack on the P-site carbonyl-carbon, guide
      these motions. Solvent mediated hydrogen transfer appears to facilitate peptide
      bond formation in conjunction with the spiral rotation. The detection of similar
      two-fold symmetry-related regions in all known structures of the large ribosomal
      subunit, indicate the universality of this mechanism, and emphasizes the
      significance of the ribosomal template for the precise alignment of the
      substrates as well as for accurate and efficient translocation. The symmetry
      related region may also be involved in regulatory tasks, such as signal
      transmission between the ribosomal features facilitating the entrance and the
      release of the tRNA molecules. The protein exit tunnel is an additional feature
      that has a role in cellular regulation. We showed by crystallographic methods
      that this tunnel is capable of undergoing conformational oscillations and
      correlated the tunnel mobility with sequence discrimination, gating and
      intracellular regulation.

PMID- 12787021
TI  - The crystal structure of annexin Gh1 from Gossypium hirsutum reveals an unusual
      S3 cluster.
AB  - The three-dimensional crystal structure of recombinant annexin Gh1 from Gossypium
      hirsutum (cotton fibre) has been determined and refined to the final R-factor of
      0.219 at the resolution of 2.1 A. This plant annexin consists of the typical
      'annexin fold' and is similar to the previously solved bell pepper annexin
      Anx24(Ca32), but significant differences are seen when compared to the structure
      of nonplant annexins. A comparison with the structure of the mammalian annexin
      AnxA5 indicates that canonical calcium binding is geometrically possible within
      the membrane loops in domains I and II of Anx(Gh1) in their present conformation.
      All plant annexins possess a conserved tryptophan residue in the AB loop of the
      first domain; this residue was found to adopt both a loop-in and a loop-out
      conformation in the bell pepper annexin Anx24(Ca32). In Anx(Gh1), the conserved
      tryptophan residue is in a surface-exposed position, half way between both
      conformations observed in Anx24(Ca32). The present structure reveals an unusual
      sulfur cluster formed by two cysteines and a methionine in domains II and III,
      respectively. While both cysteines adopt the reduced thiolate forms and are
      separated by a distance of about 5.5 A, the sulfur atom of the methionine residue
      is in their close vicinity and apparently interacts with both cysteine sulfur
      atoms. While the cysteine residues are conserved in at least five plant annexins
      and in several mammalian members of the annexin family of proteins, the
      methionine residue is conserved only in three plant proteins. Several of these
      annexins carrying the conserved residues have been implicated in oxidative stress
      response. We therefore hypothesize that the cysteine motif found in the present
      structure, or possibly even the entire sulfur cluster, forms the molecular basis
      for annexin function in oxidative stress response.

PMID- 12787022
TI  - Existence of novel beta-1,2 linkage-containing side chain in the mannan of
      Candida lusitaniae, antigenically related to Candida albicans serotype A.
AB  - The antigenicity of Candida lusitaniae cells was found to be the same as that of
      Candida albicans serotype A cells, i.e. both cell wall mannans react with factors
      1, 4, 5, and 6 sera of Candida Check. However, the structure of the mannan of C.
      lusitaniae was significantly different from that of C. albicans serotype A, and
      we found novel beta-1,2 linkages among the side-chain oligosaccharides, Manbeta1-
      >2Manbeta1--> 2Manalpha1-->2Manalpha1-->2Man (LM5), and Manbeta1-->2Man-beta1-
      >2Manbeta1-->2Manalpha1-->2Manalpha1-->2Man (LM6). The assignment of these
      oligosaccharides suggests that the mannoheptaose containing three beta-1,2
      linkages obtained from the mannan of C. albicans in a preceding study consisted
      of isomers. The molar ratio of the side chains of C. lusitaniae mannan was
      determined from the complete assignment of its H-1 and H-2 signals and these
      signal dimensions. More than 80% of the oligomannosyl side chains contained beta
      1,2-linked mannose units; no alpha-1,3 linkages or alpha-1,6-linked branching
      points were found in the side chains. An enzyme-linked immunosorbent inhibition
      assay using oligosaccharides indicated that LM5 behaves as factor 6, which is the
      serotype A-specific epitope of C. albicans. Unexpectedly, however, LM6 did not
      act as factor 6.

PMID- 12787023
TI  - Probing the interface between factor Xa and tissue factor in the quaternary
      complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor.
AB  - Blood coagulation is triggered by the formation of a complex between factor VIIa
      (FVIIa) and its cofactor, tissue factor (TF). TF-FVIIa is inhibited by tissue
      factor pathway inhibitor (TFPI) in two steps: first TFPI is bound to the active
      site of factor Xa (FXa), and subsequently FXa-TFPI exerts feedback inhibition of
      TF-FVIIa. The FXa-dependent inhibition of TF-FVIIa activity by TFPI leads to
      formation of the quaternary complex TF-FVIIa-FXa-TFPI. We used site-directed
      fluorescence probing to map part of the region of soluble TF (sTF) that interacts
      with FXa in sTF-FVIIa-FXa-TFPI. We found that the C-terminal region of sTF,
      including positions 163, 166, 200 and 201, is involved in binding to FXa in the
      complex, and FXa, most likely via its Gla domain, is also in contact with the Gla
      domain of FVIIa in this part of the binding region. Furthermore, a region that
      includes the N-terminal part of the TF2 domain and the C-terminal part of the TF1
      domain, i.e. the residues 104 and 197, participates in the interaction with FXa
      in the quaternary complex. Moreover, comparisons of the interaction areas between
      sTF and FX(a) in the quaternary complex sTF-FVIIa-FXa-TFPI and in the ternary
      complexes sTF-FVII-FXa or sTF-FVIIa-FX demonstrated large similarities.

PMID- 12787024
TI  - Amino acid residues on the surface of soybean 4-kDa peptide involved in the
      interaction with its binding protein.
AB  - Soybean 4-kDa peptide, a hormone-like peptide, is a ligand for the 43-kDa protein
      in legumes that functions as a protein kinase and controls cell proliferation and
      differentiation. As this peptide stimulates protein kinase activity, the
      interaction between the 4-kDa peptide (leginsulin) and the 43-kDa protein is
      considered important for signal transduction. However, the mechanism of
      interaction between the 4-kDa peptide and the 43-kDa protein is not clearly
      understood. We therefore investigated the binding mechanism between the 4-kDa
      peptide and the 43-kDa protein, by using gel-filtration chromatography and dot
      blot immunoanalysis, and found that the 4-kDa peptide bound to the dimer form of
      the 43-kDa protein. Surface plasmon resonance analysis was then used to explore
      the interaction between the 4-kDa peptide and the 43-kDa protein. To identify the
      residues of the 4-kDa peptide involved in the interaction with the 43-kDa
      protein, alanine-scanning mutagenesis of the 4-kDa peptide was performed. The 4
      kDa peptide-expression system in Escherichia coli, which has the ability to
      install disulfide bonds into the target protein in the cytoplasm, was employed to
      produce the 4-kDa peptide and its variants. Using mass spectrometry, the
      expressed peptides were confirmed as the oxidized forms of the native peptide.
      Surface plasmon resonance analysis showed that the C-terminal hydrophobic area of
      the 4-kDa peptide plays an important role in binding to the 43-kDa protein.

PMID- 12787025
TI  - AtCYS1, a cystatin from Arabidopsis thaliana, suppresses hypersensitive cell
      death.
AB  - In plants, cysteine protease inhibitors are involved in the regulation of protein
      turnover and play an important role in resistance against insects and pathogens.
      AtCYS1 from Arabidopsis thaliana encodes a protein of 102 amino acids that
      contains the conserved motif of cysteine protease inhibitors belonging to the
      cystatin superfamily (Gln-Val-Val-Ala-Gly). Recombinant A. thaliana cystatin-1
      (AtCYS1) was expressed in Escherichia coli and purified. AtCYS1 inhibits the
      catalytic activity of papain (Kd = 4.0 x 10-2 micro m, at pH 7.0 and 25 degrees
      C), generally taken as a molecular model of cysteine proteases. The molecular
      bases for papain inhibition by AtCYS1 have been analysed taking into account the
      three-dimensional structure of the papain-stefin B complex. AtCYS1 is
      constitutively expressed in roots and in developing siliques of A. thaliana. In
      leaves, AtCYS1 is strongly induced by wounding, by challenge with avirulent
      pathogens and by nitric oxide (NO). The overexpression of AtCYS1 blocks cell
      death activated by either avirulent pathogens or by oxidative and nitrosative
      stress in both A. thaliana suspension cultured cells and in transgenic tobacco
      plants. The suppression of the NO-mediated cell death in plants overexpressing
      AtCYS1 provides the evidence that NO is not cytotoxic for the plant, indicating
      that NO functions as cell death trigger through the stimulation of an active
      process, in which cysteine proteases and theirs proteinaceous inhibitors appear
      to play a crucial role.

PMID- 12787026
TI  - The molecular chaperone alpha-crystallin incorporated into red cell ghosts
      protects membrane Na/K-ATPase against glycation and oxidative stress.
AB  - Alpha-crystallin, a molecular chaperone and lens structural protein protects
      soluble enzymes against heat-induced aggregation and inactivation by a variety of
      molecules. In this study we investigated the chaperone function of alpha
      crystallin in a more physiological system in which alpha-crystallin was
      incorporated into red cell 'ghosts'. Its ability to protect the intrinsic
      membrane protein Na/K-ATPase from external stresses was studied. Red cell ghosts
      were created by lysing the red cells and removing cytoplasmic contents by size
      exclusion chromatography. The resulting ghost cells retain Na/K-ATPase activity.
      alpha-Crystallin was incorporated in the cells on resealing and the activity of
      Na/K-ATPase assessed by ouabain-sensitive 86Rb uptake. Incubation with fructose,
      hydrogen peroxide and methylglyoxal (compounds that have been implicated in
      diabetes and cataract formation) were used to test inactivation of the Na/K pump.
      Intracellular alpha-crystallin protected against the decrease in ouabain
      sensitive 86Rb uptake, and therefore against inactivation induced by all external
      modifiers, in a dose-dependent manner.

PMID- 12787027
TI  - Interflavin electron transfer in human cytochrome P450 reductase is enhanced by
      coenzyme binding. Relaxation kinetic studies with coenzyme analogues.
AB  - The role of coenzyme binding in regulating interflavin electron transfer in human
      cytochrome P450 reductase (CPR) has been studied using temperature-jump
      spectroscopy. Previous studies [Gutierrez, A., Paine, M., Wolf, C.R., Scrutton,
      N.S., & Roberts, G.C.K. Biochemistry (2002) 41, 4626-4637] have shown that the
      observed rate, 1/tau, of interflavin electron transfer (FADsq - FMNsq-->FADox -
      FMNhq) in CPR reduced at the two-electron level with NADPH is 55 +/- 2 s-1,
      whereas with dithionite-reduced enzyme the observed rate is 11 +/- 0.5 s-1,
      suggesting that NADPH (or NADP+) binding has an important role in controlling the
      rate of internal electron transfer. In relaxation experiments performed with CPR
      reduced at the two-electron level with NADH, the observed rate of internal
      electron transfer (1/tau = 18 +/- 0.7 s-1) is intermediate in value between those
      seen with dithionite-reduced and NADPH-reduced enzyme, indicating that the
      presence of the 2'-phosphate is important for enhancing internal electron
      transfer. To investigate this further, temperature jump experiments were
      performed with dithionite-reduced enzyme in the presence of 2',5'-ADP and 2'-AMP.
      These two ligands increase the observed rate of interflavin electron transfer in
      two-electron reduced CPR from 1/tau = 11 s-1 to 35 +/- 0.2 s-1 and 32 +/- 0.6 s
      1, respectively. Reduction of CPR at the two-electron level by NADPH, NADH or
      dithionite generates the same spectral species, consistent with an electron
      distribution that is equivalent regardless of reductant at the initiation of the
      temperature jump. Spectroelectrochemical experiments establish that the redox
      potentials of the flavins of CPR are unchanged on binding 2',5'-ADP, supporting
      the view that enhanced rates of interdomain electron transfer have their origin
      in a conformational change produced by binding NADPH or its fragments. Addition
      of 2',5'-ADP either to the isolated FAD-domain or to full-length CPR (in their
      oxidized and reduced forms) leads to perturbation of the optical spectra of both
      the flavins, consistent with a conformational change that alters the environment
      of these redox cofactors. The binding of 2',5'-ADP eliminates the unusual
      dependence of the observed flavin reduction rate on NADPH concentration (i.e.
      enhanced at low coenzyme concentration) observed in stopped-flow studies. The
      data are discussed in the context of previous kinetic studies and of the
      crystallographic structure of rat CPR.

PMID- 12787028
TI  - 31P NMR studies of energy metabolism in xanthosine-5'-monophosphate overproducing
      Corynebacterium ammoniagenes.
AB  - Corynebacterium ammoniagenes is an overproducer of xanthosine-5'-monophosphate
      (XMP) by consuming either glcose (glc) or glutamic acid (glu). Its energy
      metabolism was studied in vivo using 31P NMR spectroscopy coupled with a
      circulating fermentation system (CFS). CFS enabled us to validate directly the
      cellular dependency on carbon sources and changes in biomolecules produced
      according to alterations in the cellular energetic status. For the most efficient
      XMP production, the glutamic acid and glcose molar ratios (glu/glc) in the medium
      were adjusted to a molar ratio of 0.31. The 31P NMR illustrated the two distinct
      phases of the cellular energetic status due to the availability of the substrates
      from the medium. In the earlier phase, both glc and glu were utilized, resulting
      in average ATP and ADP concentrations in cells of 0.50 +/- 0.17 micro mol.g-1 of
      dry cell weight (DCW) and an undetermined level, respectively. The ADP
      concentration in the later phase increased to 2.15 +/- 1.30 micro mol.g-1 of DCW,
      while the ATP concentration decreased to an undetectable level in association
      with a remarkable decrease in XMP production. This decrease in the XMP-producing
      ability was associated with an increase in production of the by-product
      hypoxanthine. Because glu was found to be consumed completely during the earlier
      phase, glc was the only available substrate in the later phases. These findings
      by in vivo NMR indicate that changes in the carbon metabolism profoundly affect
      XMP production by C. ammoniagenes.

PMID- 12787029
TI  - N-Glycan structures of squid rhodopsin.
AB  - To determine the glycoforms of squid rhodopsin, N-glycans were released by
      glycoamidase A digestion, reductively aminated with 2-aminopyridine, and then
      subjected to 2D HPLC analysis [Takahashi, N., Nakagawa, H., Fujikawa, K.,
      Kawamura, Y. & Tomiya, N. (1995) Anal. Biochem.226, 139-146]. The major glycans
      of squid rhodopsin were shown to possess the alpha1-3 and alpha1-6 difucosylated
      innermost GlcNAc residue found in glycoproteins produced by insects and
      helminths. By combined use of 2D HPLC, electrospray ionization-mass spectrometry
      and permethylation and gas chromatography-electron ionization mass spectrometry
      analyses, it was revealed that most (85%) of the N-glycans exhibit the novel
      structure Manalpha1-6(Manalpha1-3)Manbeta1-4GlcNAcbeta1-4(Galbeta1-4Fucalpha1
      6)(Fucalpha1-3)GlcNAc.

PMID- 12787030
TI  - Identification, cloning and characterization of two thioredoxin h isoforms,
      HvTrxh1 and HvTrxh2, from the barley seed proteome.
AB  - Two thioredoxin h isoforms, HvTrxh1 and HvTrxh2, were identified in two and one
      spots, respectively, in a proteome analysis of barley (Hordeum vulgare) seeds
      based on 2D gel electrophoresis and MS. HvTrxh1 was observed in 2D gel patterns
      of endosperm, aleurone layer and embryo of mature barley seeds, and HvTrxh2 was
      present mainly in the embryo. During germination, HvTrxh2 decreased in abundance
      and HvTrxh1 decreased in the aleurone layer and endosperm but remained at high
      levels in the embryo. On the basis of MS identification of the two isoforms,
      expressed sequence tag sequences were identified, and cDNAs encoding HvTrxh1 and
      HvTrxh2 were cloned by RT-PCR. The sequences were 51% identical, but showed higer
      similarity to thioredoxin h isoforms from other cereals, e.g. rice Trxh (74%
      identical with HvTrxh1) and wheat TrxTa (90% identical with HvTrxh2). Recombinant
      HvTrxh1, HvTrxh2 and TrxTa were produced in Escherichia coli and purified using a
      three-step procedure. The activity of the purified recombinant thioredoxin h
      isoforms was demonstrated using insulin and barley alpha-amylase/subtilisin
      inhibitor as substrates. HvTrxh1 and HvTrxh2 were also efficiently reduced by
      Arabidopsis thaliana NADP-dependent thioredoxin reductase (NTR). The biochemical
      properties of HvTrxh2 and TrxTa were similar, whereas HvTrxh1 had higher insulin
      reducing activity and was a better substrate for Arabidopsis NTR than HvTrxh2,
      with a Km of 13 micro m compared with 44 micro m for HvTrxh2. Thus, barley seeds
      contain two distinct thioredoxin h isoforms which differ in temporal and spatial
      distribution and kinetic properties, suggesting that they may have different
      physiological roles.

PMID- 12787031
TI  - Dynamic model of Escherichia coli tryptophan operon shows an optimal structural
      design.
AB  - A mathematical model has been developed to study the effect of external
      tryptophan on the trp operon. The model accounts for the effect of feedback
      repression by tryptophan through the Hill equation. We demonstrate that the trp
      operon maintains an intracellular steady-state concentration in a fivefold range
      irrespective of extracellular conditions. Dynamic behavior of the trp operon
      corresponding to varying levels of extracellular tryptophan illustrates the
      adaptive nature of regulation. Depending on the external tryptophan level in the
      medium, the transient response ranges from a rapid and underdamped to a sluggish
      and highly overdamped response. To test model fidelity, simulation results are
      compared with experimental data available in the literature. We further
      demonstrate the significance of the biological structure of the operon on the
      overall performance. Our analysis suggests that the tryptophan operon has evolved
      to a truly optimal design.

PMID- 12787032
TI  - Expression, localization and potential physiological significance of alcohol
      dehydrogenase in the gastrointestinal tract.
AB  - ADH1 and ADH4 are the major alcohol dehydrogenases (ADH) in ethanol and retinol
      oxidation. ADH activity and protein expression were investigated in rat
      gastrointestinal tissue homogenates by enzymatic and Western blot analyses. In
      addition, sections of adult rat gastrointestinal tract were examined by in situ
      hybridization and immunohistochemistry. ADH1 and ADH4 were detected along the
      whole tract, changing their localization and relative content as a function of
      the area studied. While ADH4 was more abundant in the upper (esophagus and
      stomach) and lower (colorectal) regions, ADH1 was predominant in the intestine
      but also present in stomach. Both enzymes were detected in mucosa but, in
      general, ADH4 was found in outer cell layers, lining the lumen, while ADH1 was
      detected in the inner cell layers. Of interest were the sharp discontinuities in
      the expression found in the pyloric region (ADH1) and the gastroduodenal junction
      (ADH4), reflecting functional changes. The precise localization of ADH in the gut
      reveals the cell types where active alcohol oxidation occurs during ethanol
      ingestion, providing a molecular basis for the gastrointestinal alcohol
      pathology. Localization of ADH, acting as retinol dehydrogenase/retinal
      reductase, also indicates sites of active retinoid metabolism in the gut,
      essential for mucosa function and vitamin A absorption.

PMID- 12787033
TI  - An 'Old World' scorpion beta-toxin that recognizes both insect and mammalian
      sodium channels.
AB  - Scorpion toxins that affect sodium channel (NaCh) gating in excitable cells are
      divided into alpha- and beta-classes. Whereas alpha-toxins have been found in
      scorpions throughout the world, anti-mammalian beta-toxins have been assigned,
      thus far, to 'New World' scorpions while anti-insect selective beta-toxins
      (depressant and excitatory) have been described only in the 'Old World'. This
      distribution suggested that diversification of beta-toxins into distinct
      pharmacological groups occurred after the separation of the continents, 150
      million years ago. We have characterized a unique toxin, Lqhbeta1, from the 'Old
      World' scorpion, Leiurus quinquestriatus hebraeus, that resembles in sequence and
      activity both 'New World'beta-toxins as well as 'Old World' depressant toxins.
      Lqhbeta1 competes, with apparent high affinity, with anti-insect and anti
      mammalian beta-toxins for binding to cockroach and rat brain synaptosomes,
      respectively. Surprisingly, Lqhbeta1 also competes with an anti-mammalian alpha
      toxin on binding to rat brain NaChs. Analysis of Lqhbeta1 effects on rat brain
      and Drosophila Para NaChs expressed in Xenopus oocytes revealed a shift in the
      voltage-dependence of activation to more negative membrane potentials and a
      reduction in sodium peak currents in a manner typifying beta-toxin activity.
      Moreover, Lqhbeta1 resembles beta-toxins by having a weak effect on cardiac NaChs
      and a marked effect on rat brain and skeletal muscle NaChs. These multifaceted
      features suggest that Lqhbeta1 may represent an ancestral beta-toxin group in
      'Old World' scorpions that gave rise, after the separation of the continents, to
      depressant toxins in 'Old World' scorpions and to various beta-toxin subgroups in
      'New World' scorpions.

PMID- 12787034
TI  - Structural elucidation of polysaccharide part of glycoconjugate from Treponema
      medium ATCC 700293.
AB  - Glycoconjugates are distributed on the cell surfaces of some small-sized
      treponemes and have been reported to be completely different from
      lipopolysaccharides. We separated a glycoconjugate fraction from Treponema medium
      ATCC 700293, a medium-sized oral spirochete, to assess its immunobiological
      activities and elucidate the chemical structure of its polysaccharide part using
      phenol/water extraction, hydrophobic chromatography, and gel filtration. The
      glycoconjugate showed negligible or weak endotoxic and immunobiological
      properties. The chemical structure of the polysaccharide part was shown by two
      dimensional NMR and MALDI-TOF-MS to be a tetrasaccharide backbone with two amino
      acids: [-->4)beta-d-GlcpNAc3NAcA(1-->4)beta-d-ManpNAc3NAOrn(1-->3)beta-d
      GlcpNAc(1-->3)alpha-D-Fucp4NAsp(1-->] where GlcNAc3NAcA is 2,3-diacetamido-2,3
      dideoxyglucuronic acid, ManNAc3NAOrn is Ndelta-(2-acetamido-3-amino-2,3
      dideoxymannuronyl)ornithine, and Fuc4NAsp is 4-(alpha-aspartyl)amino-4,6
      dideoxygalactose.

PMID- 12787035
TI  - Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues.
AB  - Activation of a calcium-sensing receptor (Ca-SR) leads to increased intracellular
      calcium concentration and altered cellular activities. The expression of Ca-SR
      has been identified in both nonexcitable and excitable cells, including neurons
      and smooth muscle cells. Whether Ca-SR was expressed and functioning in cardiac
      myocytes remained unclear. In the present study, the transcripts of Ca-SR were
      identified in rat heart tissues using RT-PCR that was further confirmed by
      sequence analysis. Ca-SR proteins were detected in rat ventricular and atrial
      tissues as well as in isolated cardiac myocytes. Anti-(Ca-SR) Ig did not detect
      any specific bands after preadsorption with standard Ca-SR antigens. An
      immunohistochemistry study revealed the presence of Ca-SR in rat cardiac as well
      as other tissues. An increase in extracellular calcium or gadolinium induced a
      concentration-dependent sustained increase in [Ca2+]i in isolated ventricular
      myocytes from adult rats. Spermine (1-10 mm) also increased [Ca2+]i. Pre
      treatment of cardiac myocytes with thapsigargin or U73122 abolished the
      extracellular calcium, gadolinium or spermine-induced increase in [Ca2+]i. The
      blockade of Na+/Ca2+ exchanger or voltage-dependent calcium channels did not
      alter the extracellular calcium-induced increase in [Ca2+]i. Finally,
      extracellular calcium, gadolinium and spermine all increased intracellular
      inositol 1,4,5-triphosphate (IP3) levels. Our results demonstrated that Ca-SR was
      expressed in cardiac tissue and cardiomyocytes and its function was regulated by
      extracellular calcium and spermine.

PMID- 12787036
TI  - Are UV-induced nonculturable Escherichia coli K-12 cells alive or dead?
AB  - Cells that have lost the ability to grow in culture could be defined
      operationally as either alive or dead depending on the method used to determine
      cell viability. As a consequence, the interpretation of the state of
      'nonculturable' cells is often ambiguous. Escherichia coli K12 cells inactivated
      by UV-irradiation with a low (UV1) and a high (UV2) dose were used as a model of
      nonculturable cells. Cells inactivated by the UV1 dose lost 'culturability' but
      they were not lysed and maintained the capacity to respond to nutrient addition
      by protein synthesis and cell wall synthesis. The cells also retained both a high
      level of glucose transport and the capacity for metabolizing glucose. Moreover,
      during glucose incorporation, UV1-treated cells showed the capacity to respond to
      aeration conditions modifying their metabolic flux through the Embden-Meyerhof
      and pentose-phosphate pathways. However, nonculturable cells obtained by
      irradiation with the high UV2 dose showed several levels of metabolic imbalance
      and retained only residual metabolic activities. Nonculturable cells obtained by
      irradiation with UV1 and UV2 doses were diagnosed as active and inactive (dying)
      cells, respectively.

PMID- 12787037
TI  - Clinical evaluation in treatment of oral lichen planus with topical fluocinolone
      acetonide: a 2-year follow-up.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease which is
      recalcitrant to medical treatment. The purpose of this study was to compare the
      effectiveness of various forms of the topical steroid fluocinolone acetonide
      applications in patients with OLP. METHODS: Data of OLP patients were collected
      retrospectively from the chart record and the 97 OLP patients were divided into
      three groups. The first group (n = 28) was treated with a 0.1% solution of
      fluocinolone acetonide (FAS), the second group (n = 22) with 0.1% fluocinolone
      acetonide in orabase (FAO), and the third group (n = 47) with both FAS and FAO
      (FAS/FAO) throughout the study. Each group was clinically evaluated as complete
      remission (CR), partial remission (PR), or no response (NR), following the
      treatment. Also, the side-effect of oral candidiasis was recorded in each group.
      RESULTS: Two years of treatment resulted in complete remission of 77.3, 21.4, and
      17.0% of patients in the FAO, FAS, and FAS/FAO groups, respectively. There was a
      statistically significant difference in disease remission (P < 0.05), but not in
      oral candidiasis appearance (P > 0.05) among various forms of topical steroid
      application. CONCLUSION: The study concluded that FAO or FAS can produce improved
      results in the management of OLP by long-term follow-up.

PMID- 12787039
TI  - Photodynamic therapy (PDT) using topically applied delta-aminolevulinic acid
      (ALA) for the treatment of oral leukoplakia.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a non-invasive method for topical and
      selective treatment of pre-malignant lesions of oral cavity. The aim of our study
      was to determine therapeutic response to PDT in patients with oral leukoplakia.
      METHODS: Twelve patients participated in our study. Lesions affected a variety of
      intraoral sites. The most common location was buccal, gingival and mandibular
      mucosa. Patients were treated with topically applied 10% delta-aminolevulinic
      acid (ALA) and light from an argon-pumped dye laser. Irradiation was performed in
      several (6-8) sessions using light at 635 nm wavelength, delivering a total dose
      of 100 J/cm2 per session. RESULTS: A complete response was obtained in 10 out of
      12 treated patients. One recurrence was observed during 6 months. CONCLUSION:
      Photodynamic therapy appears to be a feasible alternative to conventional therapy
      of pre-malignant lesions of oral cavity.

PMID- 12787038
TI  - Systemic and topical corticosteroid treatment of oral lichen planus: a
      comparative study with long-term follow-up.
AB  - BACKGROUND: Topical corticosteroids are the mainstay treatment for oral lichen
      planus (OLP), but some authors suggest that systemic corticosteroid therapy is
      the only way to control acute presentation of OLP. METHODS: Forty-nine patients
      with histologically proven atrophic-erosive OLP were divided into two groups
      matched for age and sex. The test group (26 patients) was treated systemically
      with prednisone (50 mg/day), and afterwards with clobetasol ointment in an
      adhesive medium plus antimicotics, whereas the control group (23 patients) was
      only treated topically with clobetasol plus antimycotics. RESULTS: Complete
      remission of signs was obtained in 68.2% of the test group and 69.6% of the
      control group, respectively (P = 0.94). Similar results were obtained for
      symptoms. Follow-up showed no significant differences between the two groups. One
      third of the patients of the test group versus none in the control group
      experienced systemic side-effects (P = 0.003). CONCLUSIONS: The most suitable
      corticosteroid therapy in the management of OLP is the topical therapy, which is
      easier and more cost-effective than the systemic therapy followed by topical
      therapy.

PMID- 12787040
TI  - Auto-fluorescence spectra of oral submucous fibrosis.
AB  - BACKGROUND: Oral submucous fibrosis (OSF) is a chronic oral mucosal disease
      characterized by progressive deposition of collagen in the subepithelial
      connective tissue and epithelial atrophy. Previous studies have shown that at 330
      nm excitation, the 380- and 460-nm emission peaks of the auto-fluorescence
      spectra for oral mucosal tissues reflect the collagen content in the
      subepithelial connective tissue and the nicotinamide adenine dinucleotide
      phosphate (NADH) content in the epithelial cells, respectively. Therefore, at 330
      nm excitation OSF mucosa may have a higher 380-nm emission peak and a lower 460
      nm emission peak than the normal oral mucosa (NOM). METHODS: To test the above
      hypothesis, we measured the in vivo auto-fluorescence spectra of 59 OSF mucosal
      sites and compared the measured spectra with auto-fluorescence spectra obtained
      from 15 NOM samples from 15 healthy volunteers, five samples of friction
      hyperkeratosis (histologic diagnosis, hyperkeratosis and acanthosis) on OSF
      buccal mucosa (FHOSF), and 29 samples of oral leukoplakia (histologic diagnosis,
      hyperkeratosis and acanthosis) on OSF buccal mucosa (OLOSF). RESULTS: We found
      that the spectrum of the OSF mucosa had a significantly higher 380-nm emission
      peak and a significantly lower 460-nm emission peak than the spectra of NOM,
      FHOSF, and OLOSF samples. When the mean (+/-SD) fluorescence intensities at 380
      +/- 15 nm (I380 +/- 15 nm) and 460 +/- 15 nm (I460 +/- 15 nm) emission peaks and
      the mean ratio of I460 +/- 15 nm/I380 +/- 15 nm were compared between groups, we
      found that OSF group had a significantly higher mean value of I380 +/- 15 nm, a
      significantly lower mean value of I460 +/- 15 nm, and a significantly lower mean
      ratio of I460 +/- 15 nm/I380 +/- 15 nm than the NOM, FHOSF, and OLOSF groups (P <
      0.001). However, no significant differences in the mean values of I380 +/- 15 nm,
      I460 +/- 15 nm, and ratio of I460 +/- 15 nm/I380 +/- 15 nm were found between NOM
      and FHOSF or OLOSF samples as well as between FHOSF and OLOSF samples (P > 0.05).
      CONCLUSION: Because OSF mucosa has a very unique pattern of auto-fluorescence
      spectrum, we conclude that auto-fluorescence spectroscopy is a good method for
      real-time diagnosis of OSF.

PMID- 12787041
TI  - Shifts in cellular localization of moesin in normal oral epithelium, oral
      epithelial dysplasia, verrucous carcinoma and oral squamous cell carcinoma.
AB  - BACKGROUND: Moesin, a member of ERM (ezrin/radixin/moesin) family, links actin
      filaments of cell surface structure to the cell membrane. The purpose of the
      study is to assess the shifts in cellular distribution of moesin in normal oral
      epithelium, oral epithelial dysplasia (OED), verrucous carcinoma (VC), and oral
      squamous cell carcinoma (OSCC). METHODS: The expression of moesin was evaluated
      immunohistochemically in paraffin-embedded tissues of 59 specimens of OSCC, 35
      specimens of OED, 17 specimens of VC, and five specimens of normal oral
      epithelium. RESULTS: In the normal oral epithelia, all specimens showed a pattern
      of membranous expression against the anti-moesin antibody in the basal layer
      cells. In the OED specimens, moesin was dominantly expressed in the cell membrane
      except for the cornified layer. In VC and OSCC specimens, almost the whole of the
      carcinoma cells were stained with anti-moesin antibody. However, in OSCC samples,
      moesin was markedly expressed increasingly in the cytoplasm and decreasingly in
      the cell membrane, as compared with OED and VC. In addition, there was a
      significant correlation between the pattern of moesin expression and tumor
      differentiation in OSCC. CONCLUSIONS: Our results suggest that it is useful to
      detect the moesin expression as adjunct to screening mucosal lesions in the oral
      cavity.

PMID- 12787042
TI  - Id proteins are overexpressed in human oral squamous cell carcinomas.
AB  - BACKGROUND: The helix-loop-helix (HLH) proteins Id-1, Id-2 and Id-3 have been
      demonstrated to inhibit the activity of transcription factors and play an
      important role in regulating cell growth and tissue-specific differentiation.
      METHODS: To elucidate the involvement of Id in human oral squamous cell carcinoma
      (OSCC), we examined 83 surgical specimens and eight normal gingival mucosae for
      the expression of Id proteins by immunohistochemistry; in addition, some
      specimens of the OSCC and the normal gingivae were also examined for the
      expression of Id-1 mRNA by in situ hybridization (ISH), while Western blots were
      performed on six of the tumours and on cell lysates of five OSCC cell lines. We
      also explored the correlation between Id expressions and cellular proliferation
      indicating Ki-67 or clinical parameters. RESULTS: We discovered a higher and more
      frequent expression of Id-1 protein (27.7%) in human OSCC compared to that of Id
      2 and Id-3 proteins (6.0 and 7.2%, respectively). Western blot analysis detected
      Id-1 protein in four of six tumour samples and in all cell lines. ISH
      demonstrated strong cytoplasmic localization of Id-1 mRNA in tumour samples at
      significantly higher levels compared to those of normal gingival mucosae.
      CONCLUSION: Id-1 protein expression significantly correlates with lymph node
      status, indicating that increased Id expression may relate to the metastatic
      behaviour in human OSCC.

PMID- 12787043
TI  - Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer
      healing of the rabbit oral mucosa.
AB  - BACKGROUND: The therapies for refractory ulcers on the oral mucosa are
      symptomatic and very unsatisfactory. We hypothesized that application of growth
      factors might be able to achieve successful remission of the lesion. We evaluated
      the effects of systemic administration and topical application of epidermal
      growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound
      healing of ulcers in the rabbit gingiva. METHODS: Almost uniform round ulcers
      could be created on the gingiva of the rabbits by chemical injury with acetic
      acid. When the submandibular glands were removed or i.v. injection of cisplatin
      (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of
      the ulcers took longer than in untreated rabbits. To ascertain whether or not
      human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and
      bFGF on the proliferation of the cells derived from rabbit gingiva. We then
      applied EGF or bFGF in these impaired healing models. RESULTS: EGF and bFGF
      promoted proliferation of the fibroblasts, and EGF also promoted proliferation of
      the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic
      injections of EGF and bFGF in rabbits, which had their submandibular glands
      removed, and topical application of bFGF accelerated healing of ulcers created in
      rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote
      the healing of ulcers was much greater than that of EGF. CONCLUSION: Basic FGF
      may be effective for refractory oral mucosal lesions.

PMID- 12787044
TI  - Multinucleated giant cells in various forms of giant cell containing lesions of
      the jaws express features of osteoclasts.
AB  - BACKGROUND: The nature and the mechanism involved in the formation of the
      multinucleated giant cells (MGCs) in various giant cell-containing lesions of the
      jaws are not fully understood. The aim of this study is to clarify the
      osteoclastic features of the MGCs in central giant cell granuloma (CGCG),
      peripheral giant cell granuloma (PGCG), cherubism, and aneurysmal bone cyst
      (ABC), and the mechanism underlying the interrelations between cellular
      components in the formation of the MGCs. METHODS: Immunohistochemical study with
      a panel of antibodies including vacuolar H+-ATPase (V-ATPase), carbonic anhydrase
      II (CA II), Cathepsin K, matrix metalloproteinases-9 (MMP-9), CD68, and
      proliferating cell nuclear antigen (PCNA), and enzyme histochemical staining for
      tartarate-resistant acid phosphatase (TRAP) were applied on a total number of 53
      cases of giant cell-containing lesions including CGCG (n = 34), PGCG (n = 6),
      cherubism (n = 7), and ABC (n = 6). In situ hybridization was also carried out to
      detect the mRNA expression of the receptor activator of NF-kappaB ligand (RANKL),
      a newly identified cytokine that is shown to be essential in the
      osteoclastogenesis, its receptor RANK (receptor activator of NF-kappaB ligand),
      and its decoy receptor OPG (osteoprotegerin) in these four types of lesions.
      RESULTS: Immunohistochemical and enzyme histochemical studies showed that both
      the MGCs and a fraction of mononuclear cells in these lesions were strongly
      positive for TRAP, V-ATPase, CA II, Cathepsin K, MMP-9, and CD68, while the
      spindle-shaped mononuclear cells were positive for PCNA. The results with in situ
      hybridization indicated that RANKL mRNA was mainly expressed in the spindle
      mononuclear cells while OPG was extensively distributed in both the MGCs and the
      mononuclear cells. RANK mRNA was expressed in the MGCs and some round mononuclear
      cells. CONCLUSIONS: These results suggest that MGCs in the four types of giant
      cell-containing lesions of the jaws show characteristics of the osteoclast
      phenotype. The mononuclear stromal cells, which show TRAP positively, may be the
      precursors of the MGCs. RANKL, OPG, and RANK expressed in these lesions may play
      important roles in the formation of the MGCs. The similar characteristics and
      mechanisms in the differentiation of MGCs in these lesions also suggest that
      there might be a similar kind of pathogenesis involved in the formation of the
      MGCs in these lesions

PMID- 12787045
TI  - Ameloblastomatous calcifying odontogenic cyst: a rare histologic variant.
AB  - Calcifying odontogenic cyst (COC) is an uncommon developmental odontogenic cyst
      first described by Gorlin in 1962. It is considered as extremely rare and
      accounts for only 1% of jaw cysts reported. Because of its diverse
      histopathology, there has always been confusion about its nature as a cyst,
      neoplasm or hamartoma. Several subclassifications have been proposed. Here, we
      present a case of calcifying odontogenic cyst with ameloblastic proliferation -
      an extremely rare histologic variant. The classical histologic features of the
      lining epithelium in the form of cords and presence of characteristic ghost cells
      were seen along with ameloblastomatous proliferations. Ameloblastomatous COC
      microscopically resembles unicystic ameloblastoma except for the ghost cells and
      calcifications within the proliferative epithelium. The nature of the COC is
      controversial. The case is presented here for its rarity, and difference between
      ameloblastomatous COC and ameloblastoma ex COC has been emphasized.

PMID- 12787046
TI  - Intermittent footshock facilitates dendritic vasopressin release but suppresses
      vasopressin synthesis within the rat supraoptic nucleus.
AB  - Emotional stress inhibits vasopressin release from the pituitary but may
      facilitate its release from the dendrites in the hypothalamus. We examined
      effects of intermittently applied footshock upon the amount of vasopressin
      heteronuclear RNA in the hypothalamus. The footshock decreased plasma vasopressin
      concentration but increased its extracellular concentration within the supraoptic
      nucleus. The contents of the vasopressin heteronuclear RNA in the supraoptic
      nucleus were significantly decreased after the shock. These data suggest that
      intermittent footshock decreases not only vasopressin release from the axon
      terminals in the pituitary, but also vasopressin synthesis in the cell bodies in
      the hypothalamus while the stimulus facilitates vasopressin release from the
      dendrites in the hypothalamus. The data also suggest differential control of
      dendritic vasopressin release and synthesis in the hypothalamus.

PMID- 12787047
TI  - Hypothalamic-pituitary-adrenal responses to centrally administered orexin-A are
      suppressed in pregnant rats.
AB  - Orexins are hypothalamic neuropeptides that stimulate arousal and food intake but
      also activate the hypothalamic-pituitary-adrenal (HPA) axis. During late
      pregnancy in the rat, the responsiveness of the HPA axis to stressors is
      attenuated, and thus we investigated HPA axis responses to centrally administered
      orexin-A during pregnancy. Intracerebroventricular injection of orexin-A (0.5
      micro g, 140 pmol) significantly increased plasma adrenocorticotropic hormone and
      corticosterone concentration within 10 min in virgin female Sprague-Dawley rats,
      but had no effect in day 21 pregnant rats. Orexin-A significantly increased
      corticotropin-releasing hormone (CRH) mRNA expression, measured by in situ
      hybridization, in the paraventricular nucleus (PVN) of the virgin group but not
      in the pregnant group. Thus, the responsiveness of PVN CRH neurones to orexin-A,
      and hence the pituitary-adrenal axis, is markedly reduced in pregnancy. This may
      favour anabolic adaptations in pregnancy.

PMID- 12787048
TI  - Effects of novelty stress on neuroendocrine activities and running performance in
      thoroughbred horses.
AB  - This study investigated the effects of novelty stress on neuroendocrine
      activities and running performance in Thoroughbred horses. First, to examine the
      neuroendocrine responses to novelty stress, we exposed horses to two types of
      novel environmental stimuli (audiovisual or novel field stimuli). After the
      stimuli, plasma concentrations of vasopressin, catecholamines and
      adrenocorticotropin (ACTH), as well as heart rates, were significantly increased
      in each experiment. Second, we investigated neuroendocrine activities during
      incremental exercise. Plasma concentrations of vasopressin, catecholamines, ACTH
      and blood lactate increased as the exercise load increased. Finally, we
      investigated the effects of novelty stimuli on neuroendocrine activities and
      running performance during supra-maximal exercise (110% VHRmax). When the novelty
      stimuli were presented to horses, the increases in plasma vasopressin and
      catecholamines due to exercise load were significantly smaller than those in the
      control experiments. Blood lactate during supra-maximal exercise was also
      significantly lower and total run time until exhaustion was prolonged in the
      novel environmental stimuli compared to the control. These results suggest that
      novelty stimuli facilitate vasopressin release from the posterior pituitary in
      addition to activating the sympatho-adrenomedullary and the hypothalamic
      pituitary-adrenocortical axes in thoroughbred horses, and increase exercise
      capacity, resulting in improvement of running performance during supra-maximal
      exercise.

PMID- 12787049
TI  - Activation of the hypothalamic arcuate nucleus predicts the anorectic actions of
      ciliary neurotrophic factor and leptin in intact and gold thioglucose-lesioned
      mice.
AB  - Similar to leptin, ciliary neurotrophic factor (CNTF) suppresses appetite and
      selectively reduces body fat in leptin-deficient ob/ob mice. To assess the
      relative importance of specific regions of the hypothalamus in mediating these
      effects, we administered a CNTF analogue (CNTFAx15) or leptin to mice made obese
      by administration of gold thioglucose (GTG), which destroys a well-defined
      portion of the medial basal hypothalamus. CNTFAx15 treatment reduced appetite and
      body weight in obese GTG-lesioned C57BL/6 mice, whereas leptin failed to effect
      similar changes regardless of whether treatment was initiated before or after the
      lesioned mice had become obese. Because leptin does not reduce food intake or
      body weight in most forms of obesity (a condition termed 'leptin resistance'), we
      also investigated the actions of leptin in GTG-lesioned leptin-deficient (ob/ob)
      mice. By contrast to C57BL/6 mice, leptin treatment reduced food intake and body
      weight in GTG-lesioned ob/ob mice, although the effect was attenuated. To further
      compare the neural substrates mediating the anorectic actions of leptin and CNTF,
      we determined the patterns of neurone activation induced by these proteins in the
      hypothalamus of intact and GTG-lesioned mice by staining for phosphorylated
      signal transducer and activator of transcription 3 (pSTAT3). CNTFAx15 stimulated
      robust pSTAT3 signalling in neurones of the medial arcuate nucleus in both intact
      and lesioned C57BL/6 and ob/ob mice. Leptin administration stimulated pSTAT3
      signalling in only a few neurones of the medial arcuate nucleus in intact or
      lesioned C57BL/6 mice, but elicited a robust response in intact or lesioned ob/ob
      mice. By contrast to CNTFAx15, leptin treatment also resulted in prominent
      activation of STAT3 in several areas of the hypothalamus outside the medial
      arcuate nucleus. This leptin-induced pSTAT3 signal was at least as prominent in
      intact and GTG-lesioned C57BL/6 mice as it was in ob/ob mice, and thus was not
      correlated with appetite suppression or weight loss. These results indicate that
      the medial arcuate nucleus is a key mediator of appetite suppression and weight
      loss produced by CNTF and leptin, whereas GTG-vulnerable regions play a role only
      in leptin-induced weight loss. Other regions of hypothalamus in which pSTAT3
      signal is induced by leptin may regulate energy metabolism through mechanisms
      other than appetite reduction.

PMID- 12787050
TI  - Regulation of rat APJ receptor messenger ribonucleic acid expression in
      magnocellular neurones of the paraventricular and supraopric nuclei by osmotic
      stimuli.
AB  - The novel apelin receptor (APJ receptor, APJR) has a restricted expression in the
      central nervous system suggestive of an involvement in the regulation of body
      fluid homeostasis. The endogenous ligand for APJR, apelin, is also highly
      concentrated in regions that are involved in the control of drinking behaviour.
      While the physiological roles of APJR and apelin are not fully known, apelin has
      been shown to stimulate drinking behaviour in rats and to have a regulatory
      effect on vasopressin release from magnocellular neurones of the hypothalamic
      paraventricular (PVN) and supraoptic (SON) nuclei. To determine the role of APJR
      in the regulation of water balance, this study examined the effects of osmotic
      stimulation on the expression of APJR mRNA in the magnocellular PVN (mPVN) and
      SON of salt-loaded and water-deprived rats. Intake of 2% NaCl and water
      deprivation for 48 h induced expression of APJR mRNA in the mPVN and SON. Using
      dual-label in situ hybridization histochemistry, we also investigated whether
      APJR is colocalized within vasopressin neurones in control, salt-loaded and water
      deprived rats. APJR mRNA was found to colocalize with a small population of
      vasopressin-containing magnocellular neurones in control and water-deprived rats.
      Salt-loading resulted in an increased colocalization of APJR and vasopressin
      mRNAs in the SON. These data verify a role for APJ receptors in body fluid
      regulation and suggest a role for apelin in the regulation of vasopressin
      containing neurones via a local autocrine/paracrine action of the peptide.

PMID- 12787051
TI  - Nitric oxide produced by a novel nitric oxide synthase isoform is necessary for
      gonadotropin-releasing hormone-induced growth hormone secretion via a cGMP
      dependent mechanism.
AB  - The involvement of nitric oxide (NO) in the regulation of goldfish growth hormone
      (GH) secretion was further characterized using primary cultures of dispersed
      goldfish pituitary cells. Western blots revealed the presence of an inducible
      nitric oxide synthase (iNOS)-like protein of approximately 120 kDa in
      cytosol/plasma membrane extracts. By contrast, brain NOS-immunoreactive proteins
      of approximately 120-140 kDa were occasionally detected in a
      cytoskeleton/organelle fraction but were absent from cytosol/plasma membrane
      extracts. The NO donor sodium nitroprusside (SNP) acutely increased GH secretion
      but this response was not observed in the presence of either a NO scavenger
      (PTIO) or a soluble guanylate cyclase inhibitor (ODQ). SNP also significantly
      increased the levels of cyclic (c)GMP in somatotrope-enriched cell populations.
      Treatments with 1400W (iNOS inhibitor), PTIO and rutin hydrate (NO scavengers)
      and ODQ abolished the acute GH-release response to two endogenous gonadotropin
      releasing hormones (GnRH). 1400W, rutin hydrate, PTIO and ODQ alone did not
      significantly alter basal GH secretion. Together, these results establish that an
      iNOS-like peptide is constitutively present in the pituitary of the goldfish.
      Furthermore, these data suggest that NO, most likely through the generation of
      cGMP, is a necessary signal transduction component of GnRH-induced GH secretion.

PMID- 12787052
TI  - Mitochondrial benzodiazepine receptors in the ventral tegmental area modulate
      sexual behaviour of cycling or hormone-primed hamsters.
AB  - Hamsters are highly dependent upon the central actions of progesterone (P4) for
      facilitation of sexual behaviour. In the ventral tegmental area (VTA), P4 has
      actions through its neurosteroid metabolite 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP). The effects of enhancing or inhibiting neurosteroidogenesis
      (and thereby 3alpha,5alpha-THP concentrations), through manipulations of
      mitochondrial benzodiazepine receptors, in the VTA on socio-sexual behaviour of
      female hamsters were examined. Intact, naturally receptive hamsters and
      ovariectomized (OVX), hormone-primed hamsters were unilaterally infused via
      chronic guide cannula to the VTA with the mitochondrial benzodiazepine receptor
      antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3
      isoquinolinecarboximide (PK-11195) or the mitochondrial benzodiazepine receptor
      agonist, N,N-dihexyl-2-(4-fluorophenyl)indole-30-acetamide (FGIN 1-27) and tested
      for sexual responsiveness and lordosis. PK-11195 (5.6, 11.2 or 22.4 nm) to the
      VTA attenuated sexual responsiveness of naturally receptive or oestradiol
      benzoate (EB) + P4-primed hamsters compared to vehicle. In addition, FGIN 1-27
      (11.4 nm) infusions to the VTA increased sexual responsiveness and lordosis of
      cycling or OVX, EB + P4-primed hamsters, compared to vehicle infusions. In OVX,
      EB + P4-primed hamsters, decrements in sexual responsiveness produced by VTA
      infusions of PK-11195 (5.6 nm) were attenuated by VTA infusions of 3alpha,5alpha
      THP. VTA infusions of PK-11195 (5.6 nm) or FGIN 1-27 (11.4 nm), respectively,
      decreased and increased midbrain levels of 3alpha,5alpha-THP compared to each
      other. Together, these findings indicate that manipulating actions of
      mitochondrial benzodiazepine receptors in the VTA can augment and inhibit
      neurosteroidogenesis and sexual responsiveness of hormone-primed and naturally
      receptive hamsters.

PMID- 12787053
TI  - Prolactin and oxytocin interaction in the paraventricular and supraoptic nuclei:
      effects on oxytocin mRNA and nitric oxide synthase.
AB  - We investigated the contribution of prolactin and oxytocin to the increase in
      staining for NADPH-d and oxytocin mRNA in the paraventricular nucleus (PVN) and
      supraoptic nucleus (SON) observed at the end of pregnancy, or following a steroid
      priming regimen that mimics the hormonal profile of late pregnant females.
      Ovariectomized rats received chronic implants of silastic capsules containing
      oestrogen and progesterone followed by progesterone removal. In experiment 1,
      oxytocin antagonist (OTA) was administered to rats to investigate whether
      intranuclear oxytocin release was necessary for NADPH-d staining. In experiments
      2a and b, rats received concurrent treatment with bromocryptine (0.5 mg/day) to
      suppress endogenous prolactin release, and either systemic prolactin (0.5 mg once
      daily), or prolactin (2 micro g/ micro l), or vehicle infused twice a day into
      the third ventricle, or chronic oxytocin infusion (24 ng/day) for 3 days
      following progesterone removal. Brains were then processed for NADPH-d
      histochemistry. In experiment 3, the interaction of prolactin and oxytocin on
      oxytocin mRNA within the SON and PVN was examined. NADPH-d staining in the SON
      and PVN was reduced by the highest dose of the OTA, and by bromocryptine
      treatment. Central prolactin and oxytocin replacement completely restored NADPH-d
      staining in bromocryptine-treated rats. Finally, both bromocryptine and the OTA
      suppressed oxytocin mRNA expression and prolactin replacement restored expression
      levels to that of controls. Together, these data suggest that the increased
      capacity to produce nitric oxide in the SON and PVN during late pregnancy is
      dependent on prolactin stimulating oxytocin gene mRNA and hence intranuclear
      oxytocin release.

PMID- 12787054
TI  - Links between the appetite regulating systems and the neuroendocrine
      hypothalamus: lessons from the sheep.
AB  - The hypothalamus is integral to the regulation of energy homeostasis and the
      secretion of hormones from the pituitary gland. Consequently, hypothalamic
      systems may have a dual purpose in regulating both neuroendocrine function and
      appetite. To date, most studies investigating the interface between appetite and
      hormone secretion have been performed in rats or mice that have been acutely
      fasted or baring a genetic abnormality causing either obesity or aphagia. By
      contrast, various physiological models, including chronic food-restriction or
      photoperiodically driven changes in voluntary food intake, add further
      perspective to the issue. In this regard, sheep provide an innovative model
      whereby long-term changes in body weight or extended feeding rhythms can be
      investigated. This review compares and contrasts data obtained in different
      species with regard to the neuroendocrinology of appetite, and discusses the
      benefits and knowledge gained from using various nonrodent models with a
      particular emphasis on a ruminant species.

PMID- 12787055
TI  - Creatine therapy provides neuroprotection after onset of clinical symptoms in
      Huntington's disease transgenic mice.
AB  - While there have been enormous strides in the understanding of Huntington's
      disease (HD) pathogenesis, treatment to slow or prevent disease progression
      remains elusive. We previously reported that dietary creatine supplementation
      significantly improves the clinical and neuropathological phenotype in transgenic
      HD mice lines starting at weaning, before clinical symptoms appear. We now report
      that creatine administration started after onset of clinical symptoms
      significantly extends survival in the R6/2 transgenic mouse model of HD. Creatine
      treatment started at 6, 8, and 10 weeks of age, analogous to early, middle, and
      late stages of human HD, significantly extended survival at both the 6- and 8
      week starting points. Significantly improved motor performance was present in
      both the 6- and 8-week treatment paradigms, while reduced body weight loss was
      only observed in creatine-supplemented R6/2 mice started at 6 weeks.
      Neuropathological sequelae of gross brain and neuronal atrophy and huntingtin
      aggregates were delayed in creatine-treated R6/2 mice started at 6 weeks. We show
      significantly reduced brain levels of both creatine and ATP in R6/2 mice,
      consistent with a bioenergetic defect. Oral creatine supplementation
      significantly increased brain concentrations of creatine and ATP to wild-type
      control levels, exerting a neuroprotective effect. These findings have important
      therapeutic implications, suggesting that creatine therapy initiated after
      diagnosis may provide significant clinical benefits to HD patients.

PMID- 12787056
TI  - Role of protein phosphatase 2C from bovine adrenal chromaffin cells in the
      dephosphorylation of phospho-serine 40 tyrosine hydroxylase.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of
      catecholamines. It is dephosphorylated by protein phosphatase (PP) 2A and PP2C.
      In this study we used a fixed amount of bacterially expressed rat TH (5 microM),
      phosphorylated only at serine 40 (pSer40TH), to determine the PP activities
      against this site that are present in extracts from the bovine adrenal cortex,
      adrenal medulla, adrenal chromaffin cells and rat striatum. We found that PP2C
      was the main TH phosphatase activity in extracts from the adrenal medulla and
      adrenal chromaffin cells. In adrenal cortex extracts PP2C and PP2A activities
      toward pSer40TH did not differ significantly. PP2A was the main TH phosphatase
      activity in extracts from rat striatum. Kinetic studies with extracts from
      adrenal chromaffin cells showed that when higher concentrations of pSer40TH (> 5
      microM) were used the activity of PP2C increased more than the activity of PP2A.
      PP2C was maximally activated by 1.25 mM Mn2+ and by 5 mM Mg2+ but was inhibited
      by calcium. Our data suggest a more important role for PP2C than was previously
      suggested in the dephosphorylation of serine 40 on TH.

PMID- 12787057
TI  - Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected
      in the brains of various mammalian species.
AB  - 2-Eicosa-5',8',11',14'-tetraenylglycerol (2-AG ether, HU310, noladin ether) is a
      metabolically stable ether-linked analogue of 2-arachidonoylglycerol (2-AG), an
      endogenous cannabinoid receptor ligand. 2-AG ether has been used as a valuable
      experimental tool by a number of investigators. Recently, several groups reported
      that 2-AG ether is present in mammalian brains. We examined in detail whether 2
      AG ether actually exists in the brains of various mammalian species. We found
      that 2-AG ether is not present, at least in an appreciable amount, in the rat
      brain by gas chromatography-mass spectrometry analysis and fluorometric high
      performance liquid chromatography analysis. The level of 2-AG ether in the rat
      brain was below 0.2 pmol/g brain, if at all present. Similar results were
      obtained for the mouse brain, hamster brain, guinea-pig brain and pig brain. The
      fact that 2-AG ether was not detected in the brains of various mammalian species
      is consistent with the fact that an ether bond is formed through enzymatic
      replacement of the fatty acyl moiety of 1-acyl dihydroxyacetone phosphate by a
      fatty alcohol, the resultant 1-O-alkyl dihydroxyacetone phosphate being a common
      intermediate of the biosynthesis of ether-linked lipids in mammalian tissues. It
      is rather questionable whether 2-AG ether is present in appreciable amounts in
      the brain and acts as an 'endogenous' cannabinoid receptor ligand.

PMID- 12787058
TI  - Identification of a nerve ending-enriched 29-kDa protein, labeled with [3-32P]1,3
      bisphosphoglycerate, as monophosphoglycerate mutase: inhibition by fructose-2,6
      bisphosphate via enhancement of dephosphorylation.
AB  - Glucose metabolism is of vital importance in normal brain function. Evidence
      indicates that glycolysis, in addition to production of ATP, plays an important
      role in maintaining normal synaptic function. In an effort to understand the
      potential involvement of a glycolytic intermediate(s) in synaptic function, we
      have prepared [3-32P]1,3-bisphosphoglycerate and [32P]3-phosphoglycerate and
      sought their interaction with a specific nerve-ending protein. We have found that
      a 29-kDa protein is the major component labeled with either [3-32P]1,3
      bisphosphoglycerate or [32P]3-phosphoglycerate. The protein was identified as
      monophosphoglycerate mutase (PGAM). This labeling was remarkably high in the
      brain and synaptosomal cytosol fraction, consistent with the importance of
      glycolysis in synaptic function. Of interest, fructose-2,6-bisphosphate (Fru-2,6
      P2) inhibited PGAM phosphorylation and enzyme activity. Moreover, Fru-2,6-P2
      potently stimulated release of [32P]phosphate from the 32P-labeled PGAM (EC50 = 1
      microM), suggesting that apparent reduction of PGAM phosphorylation and enzyme
      activity by Fru-2,6-P2 may be due to stimulation of dephosphorylation of PGAM.
      The significance of these findings is discussed.

PMID- 12787059
TI  - Proteomic identification of nitrated proteins in Alzheimer's disease brain.
AB  - Nitration of tyrosine in biological conditions represents a pathological event
      that is associated with several neurodegenerative diseases, such as amyotrophic
      lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). Increased
      levels of nitrated proteins have been reported in AD brain and CSF, demonstrating
      the potential involvement of reactive nitrogen species (RNS) in neurodegeneration
      associated with this disease. Reaction of NO with O2- leads to formation of
      peroxynitrite ONOO-, which following protonation, generates cytotoxic species
      that oxidize and nitrate proteins. Several findings suggest an important role of
      protein nitration in modulating the activity of key enzymes in neurodegenerative
      disorders, although extensive studies on specific targets of protein nitration in
      disease are still missing. The present investigation represents a further step in
      understanding the relationship between oxidative modification of protein and
      neuronal death in AD. We previously applied a proteomics approach to determine
      specific targets of protein oxidation in AD brain, by successfully coupling
      immunochemical detection of protein carbonyls with two-dimensional polyacrylamide
      gel electrophoresis and mass spectrometry analysis. In the present study, we
      extend our investigation of protein oxidative modification in AD brain to targets
      of protein nitration. The identification of six targets of protein nitration in
      AD brain provides evidence to the importance of oxidative stress in the
      progression of this dementing disease and potentially establishes a link between
      RNS-related protein modification and neurodegeneration.

PMID- 12787060
TI  - Brain edema induced by in vitro ischemia: causal factors and neuroprotection.
AB  - Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to
      ischemic brain injury via complex pathophysiological events, including
      excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+, and
      reactive oxygen species (ROS) generation. Each of these could also contribute to
      cerebral edema, which is the primary cause of patient mortality after stroke. In
      vitro brain slices are widely used to study ischemia. Here we introduce a slice
      model to investigate ischemia-induced edema. Significant water gain was induced
      in coronal slices of rat brain by 5 min of oxygen and glucose deprivation (OGD)
      at 35 degrees C, with progressive edema formation after return to normoxic,
      normoglycemic medium. Edema increased with increasing injury severity, determined
      by OGD duration (5-30 min). Underlying factors were assessed using glutamate
      receptor antagonists (AP5/CNQX), blockade of mitochondrial permeability
      transition [cyclosporin A (CsA) versus FK506], inhibition of Na+/Ca2+ exchange
      (KB-R7943), and ROS scavengers (ascorbate, Trolox, dimethylthiourea, Tempol). All
      agents except KB-R7943 and FK506 significantly attenuated edema when applied
      after OGD; KB-R7943 was effective when applied before OGD. Significantly,
      complete prevention of ischemia-induced edema was achieved with a cocktail of
      AP5/CNQX, CsA and Tempo applied after OGD, which demonstrates the involvement of
      multiple, additive mechanisms. The efficacy of this cocktail further shows the
      potential value of combination therapies for the treatment of cerebral ischemia.

PMID- 12787061
TI  - Interleukin-18 induces expression and release of cytokines from murine glial
      cells: interactions with interleukin-1 beta.
AB  - Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important
      mediator of peripheral inflammation and host defence responses. IL-1 is a key
      proinflammatory cytokine in the brain, but the role of IL-18 in the CNS is not
      yet clear. The objective of this study was to investigate the actions of IL-18 on
      mouse glial cells. IL-18 induced intracellular expression of IL-1 alpha and proIL
      1 beta, and release of IL-6 from mixed glia. Treatment of lipopolysaccharide
      primed microglia with adenosine triphosphate (ATP), an endogenous secondary
      stimulus, induced IL-1 beta and IL-18 release. Although deletion of the IL-18
      gene did not affect IL-1 beta expression or release in this experimental
      paradigm, IL-1 beta knockout microglia released significantly less IL-18 compared
      to wild-type microglia. In addition, ATP induced release of mature IL-1 beta from
      IL-18-primed microglia. These data suggest that IL-18 may contribute to
      inflammatory responses in the brain, and demonstrate that, in spite of several
      common features, IL-18 and IL-1 beta differ in their regulation and actions.

PMID- 12787062
TI  - c-Fos is essential for the response of the tyrosine hydroxylase gene to
      depolarization or phorbol ester.
AB  - Tyrosine hydroxylase (TH) gene transcription rate increases in response to
      numerous pharmacological and physiological stimuli. The AP1 site within the TH
      gene proximal promoter is thought to play an important role in mediating many of
      these responses; however, it is unclear which AP1 factors are required. To
      investigate whether c-Fos is essential for the response of the TH gene to
      different stimuli, c-Fos-deficient PC12 cell lines were produced utilizing an
      antisense RNA strategy. In these cell lines, stimulus-induced increases in c-Fos
      protein levels were dramatically attenuated, while c-Jun and CREB levels remained
      unchanged. TH gene transcription rate increased from four- to eight-fold in
      control cells after treatment with either 50 mM KCl or TPA. These responses were
      dramatically decreased in the c-Fos-deficient cell lines. In contrast, c-Fos down
      regulation had little effect on the response of the TH gene to forskolin.
      Stimulation of TH gene promoter activity, which was observed in control cell
      lines treated with either 50 mm KCl or TPA was also dramatically inhibited in the
      c-Fos-deficient cells. These results suggest that c-Fos induction is essential
      for maximal stimulation of the TH gene in response to either depolarization or
      PKC activation in PC12 cells.

PMID- 12787063
TI  - Cyclosporin A prevents calpain activation despite increased intracellular calcium
      concentrations, as well as translocation of apoptosis-inducing factor, cytochrome
      c and caspase-3 activation in neurons exposed to transient hypoglycemia.
AB  - Blockade of mitochondrial permeability transition protects against hypoglycemic
      brain damage. To study the mechanisms downstream from mitochondria that may cause
      neuronal death, we investigated the effects of cyclosporin A on subcellular
      localization of apoptosis-inducing factor and cytochrome c, activation of the
      cysteine proteases calpain and caspase-3, as well as its effect on brain
      extracellular calcium concentrations. Redistribution of cytochrome c occurred at
      30 min of iso-electricity, whereas translocation of apoptosis-inducing factor to
      nuclei occurred at 30 min of recovery following 30 min of iso-electricity. Active
      caspase-3 and calpain-induced fodrin breakdown products were barely detectable in
      the dentate gyrus and CA1 region of the hippocampus of rat brain exposed to 30 or
      60 min of insulin-induced hypoglycemia. However, 30 min or 3 h after recovery of
      blood glucose levels, fodrin breakdown products and active caspase-3 markedly
      increased, concomitant with a twofold increase in caspase-3-like enzymatic
      activity. When rats were treated with neuroprotective doses of cyclosporin A, but
      not with FK 506, the redistribution of apoptosis-inducing factor and cytochrome c
      was reduced and fodrin breakdown products and active caspase-3 immuno-reactivity
      was diminished whereas the extracellular calcium concentration was unaffected. We
      conclude that hypoglycemia leads to mitochondrial permeability transition which,
      upon recovery of energy metabolism, mediates the activation of caspase-3 and
      calpains, promoting cell death.

PMID- 12787064
TI  - Dopaminergic neuronal differentiation from rat embryonic neural precursors by
      Nurr1 overexpression.
AB  - In vitro expanded CNS precursors could provide a renewable source of dopamine
      (DA) neurons for cell therapy in Parkinson's disease. Functional DA neurons have
      been derived previously from early midbrain precursors. Here we demonstrate the
      ability of Nurr1, a nuclear orphan receptor essential for midbrain DA neuron
      development in vivo, to induce dopaminergic differentiation in naive CNS
      precursors in vitro. Independent of gestational age or brain region of origin,
      Nurr1-induced precursors expressed dopaminergic markers and exhibited
      depolarization-evoked DA release in vitro. However, these cells were less mature
      and secreted lower levels of DA than those derived from mesencephalic precursors.
      Transplantation of Nurr1-induced DA neuron precursors resulted in limited
      survival and in vivo differentiation. No behavioral improvement in apomorphine
      induced rotation scores was observed. These results demonstrate that Nurr1
      induces dopaminergic features in naive CNS precursors in vitro. However,
      additional factors will be required to achieve in vivo function and to unravel
      the full potential of neural precursors for cell therapy in Parkinson's disease.

PMID- 12787065
TI  - Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro:
      opposite effects of lipopolysaccharide.
AB  - Apolipoprotein E (apoE) and apoJ are lipid carriers produced in the brain
      primarily by glial cells. A variety of glial-activating stimuli induce a parallel
      upregulation of both apolipoproteins expression in vivo and in vitro. To further
      characterize the cell type and mechanisms by which apoE and apoJ expression are
      upregulated in activated glia, mixed glial cultures from neonatal rat cortex were
      treated with the endotoxin lipopolysaccharide (LPS). LPS induced dose-dependent
      increases in apoJ and decreases in apoE expression and secretion with maximum
      effects at 1-10 ng/mL and 0.1-1 microg/mL, respectively. Experiments with
      enriched astroglial and microglial cultures demonstrated that apoE and apoJ
      expression are predominantly microglial and astroglial, respectively. Given the
      pivotal role that nuclear factor-kappa B (NF-kappa B) plays in glial activation,
      we assessed its possible role in mediating apoE and apoJ expression by activated
      glia. LPS robustly increased NF-kappa B activation in mixed glial cultures. Two
      NF-kappa B inhibitors, aspirin (10 mM) and MG-132 (0.1 microM), blocked basal
      apoE and apoJ secretion as well as LPS-induced apoJ secretion. These data
      demonstrate that glial apoE and apoJ expression are independently regulated by
      LPS in microglia and astroglia, respectively, and that activated microglia are
      the predominant source of apoE in mixed glial cultures. The transcription factor
      NF-kappa B appears to be a critical mediator of LPS-stimulated apoJ expression
      from astroglia.

PMID- 12787066
TI  - Alpha-synuclein up-regulates expression of caveolin-1 and down-regulates
      extracellular signal-regulated kinase activity in B103 neuroblastoma cells: role
      in the pathogenesis of Parkinson's disease.
AB  - alpha-Synuclein accumulation plays an important role in the pathogenesis of Lewy
      body disease (LBD) and Parkinson's disease (PD). Although the mechanisms are not
      yet clear, it is possible that dysregulation of the extracellular signal
      regulated kinase (ERK) might play a role. As caveolins form scaffolds onto which
      signaling molecules such as ERK can assemble, we propose that signaling
      alterations associated with alpha-synuclein accumulation and neurodegeneration,
      might be mediated via caveolae. Therefore, the objective of the present study was
      to investigate the potential contribution of alterations in the caveolar system
      in mediating alpha-synuclein effects on the ERK signaling pathway. For this,
      synuclein-transfected B103 neuroblastoma cells were used as a model system. In
      this cell line, caveolin-1 expression was up-regulated, whereas, ERK was down
      regulated. ERK was weakly but consistently co-immunoprecipitated with alpha
      synuclein but caveolin-1 did not co-immunoprecipitate with alpha-synuclein.
      Moreover, treatment of alpha-synuclein- overexpressing cells with caveolin-1
      antisense oligonucleotides resulted in stimulation of ERK activity, with
      amelioration of the neuritic alterations. Transduction of alpha-synuclein
      overexpressing cells, with an adenoviral vector directing the expression of ERK,
      resulted in suppression of caveolin-1 expression and re-establishment of the
      normal patterns of neurite outgrowth. These results suggest that alpha-synuclein
      may also interfere with ERK signaling by dysregulating caveolin-1 expression.
      Thus, the caveolin-1/ERK pathway could be a therapeutic target for the alpha
      synuclein-related neurodegenerative disorders.

PMID- 12787067
TI  - Use of Arc expression as a molecular marker of increased postsynaptic 5-HT
      function after SSRI/5-HT1A receptor antagonist co-administration.
AB  - An increase in central postsynaptic 5-hydroxytryptamine (5-HT) function activates
      expression of activity-related cytoskeletal protein (Arc). Here, Arc expression
      was used to test whether, in rats, co-administration of a 5-HT re-uptake
      inhibitor (paroxetine) and a 5-HT1A receptor antagonist (WAY 100635) increases
      postsynaptic 5-HT function. After pre-treatment with WAY 100635 (0.3 mg/kg s.c.),
      paroxetine (5 mg/kg s.c.) caused a threefold increase in 5-HT in prefrontal
      cortex microdialysates. In situ hybridization studies found that neither
      paroxetine (5 mg/kg s.c.) nor WAY 1000635 (0.3 mg/kg s.c.) altered Arc mRNA
      abundance in any region examined. In contrast, paroxetine (5 mg/kg s.c.)
      increased Arc mRNA after pre-treatment with WAY 100635 (0.3 mg/kg s.c.). This
      increase was apparent in cortical regions (frontal, parietal and cingulate) and
      caudate nucleus but was absent in hippocampus (CA1). Increases in Arc mRNA were
      accompanied by an increase in c-fos mRNA. The increase in Arc expression induced
      by paroxetine/WAY 100635 was abolished by the 5-HT synthesis inhibitor, p
      chlorophenylalanine (300 mg/kg i.p., daily for two days). In conclusion,
      paroxetine and WAY 100635 injected in combination (but not alone) caused a region
      specific, 5-HT-mediated increase in Arc expression. These data provide molecular
      evidence that co-administration of a 5-HT re-uptake inhibitor and 5-HT1A receptor
      antagonist increases 5-HT function at the postsynaptic level.

PMID- 12787068
TI  - A myocyte enhancer factor 2D (MEF2D) kinase activated during neuronal apoptosis
      is a novel target inhibited by lithium.
AB  - Depolarization promotes the survival of cerebellar granule neurons via activation
      of the transcription factor myocyte enhancer factor 2D (MEF2D). Removal of
      depolarization induces hyperphosphorylation of MEF2D on serine/threonine
      residues, resulting in its decreased DNA binding and susceptibility to caspases.
      The subsequent loss of MEF2-dependent gene transcription contributes to the
      apoptosis of granule neurons. The kinase(s) that phosphorylates MEF2D during
      apoptosis is currently unknown. The serine/threonine kinase, glycogen synthase
      kinase-3 beta (GSK-3 beta), plays a pro-apoptotic role in granule neurons. To
      investigate a potential role for GSK-3 beta in MEF2D phosphorylation, we examined
      the effects of lithium, a non-competitive inhibitor of GSK-3 beta, on MEF2D
      activity in cultured cerebellar granule neurons. Lithium inhibited caspase-3
      activation and chromatin condensation in granule neurons induced to undergo
      apoptosis by removal of depolarizing potassium and serum. Concurrently, lithium
      suppressed the hyperphosphorylation and caspase-mediated degradation of MEF2D.
      Moreover, lithium sustained MEF2 DNA binding and transcriptional activity in the
      absence of depolarization. Lithium also attenuated MEF2D hyperphosphorylation and
      apoptosis induced by calcineurin inhibition under depolarizing conditions, a GSK
      3 beta-independent model of neuronal death. In contrast to lithium, MEF2D
      hyperphosphorylation was not inhibited by forskolin, insulin-like growth factor
      I, or valproate, three mechanistically distinct inhibitors of GSK-3 beta. These
      results demonstrate that the kinase that phosphorylates and inhibits the pro
      survival function of MEF2D in cerebellar granule neurons is a novel lithium
      target distinct from GSK-3 beta.

PMID- 12787069
TI  - Bcl-2-related protein family gene expression during oligodendroglial
      differentiation.
AB  - Oligodendroglial lineage cells (OLC) vary in susceptibility to both necrosis and
      apoptosis depending on their developmental stages, which might be regulated by
      differential expression of Bcl-2-related genes. As an initial step to test this
      hypothesis, we examined the expression of 19 Bcl-2-related genes in purified
      cultures of rat oligodendroglial progenitors, immature and mature
      oligodendrocytes. All 'multidomain' anti-apoptotic members (Bcl-x, Bcl-2, Mcl-1,
      Bcl-w and Bcl2l10/Diva/Boo) except Bcl2a1/A1 are expressed in OLC.
      Semiquantitative and real-time RT-PCR revealed that Bcl-xL and Mcl-1 mRNAs are
      the dominant anti-apoptotic members and increase four- and twofold, respectively,
      with maturation. Bcl-2 mRNA is less abundant than Bcl-xL mRNA in progenitors and
      falls an additional 10-fold during differentiation. Bcl-w mRNA also increases,
      with significant changes in its splicing pattern, as OLC mature. Transfection
      studies demonstrated that Bcl-xL overexpression protects against kainate-induced
      excitotoxicity, whereas Bcl-2 overexpression does not. As for 'multidomain' pro
      apoptotic members (Bax, Bad and Bok/Mtd), Bax and Bak are highly expressed
      throughout differentiation. Among 'BH3 domain-only' members examined (Bim, Biklk,
      DP5/Hrk, Bad, Bid, Noxa, Puma/Bbc3, Bmf, BNip3 and BNip3L), BNip3 and Bmf mRNAs
      increase markedly during differentiation. These results provide basic information
      to guide further studies on the roles for Bcl-2-related family proteins in OLC
      death.

PMID- 12787071
TI  - Two serine residues distinctly regulate the rescue function of Humanin, an
      inhibiting factor of Alzheimer's disease-related neurotoxicity: functional
      potentiation by isomerization and dimerization.
AB  - The 24-residue peptide Humanin (HN), containing two Ser residues at positions 7
      and 14, protects neuronal cells from insults of various Alzheimer's disease (AD)
      genes and A beta. It was not known why the rescue function of (S14G)HN is more
      potent than HN by two to three orders of magnitude. Investigating the possibility
      that the post-translational modification of Ser14 might play a role, we found
      that HN with D-Ser at position 14 exerts neuroprotection more potently than HN by
      two to three orders of magnitude, whereas D-Ser7 substitution does not affect the
      rescue function of HN. On the other hand, S7A substitution nullified the HN
      function. Multiple series of experiments indicated that Ser7 is necessary for
      self-dimerization of HN, which is essential for neuroprotection by this factor.
      These findings indicate that the rescue function of HN is quantitatively
      modulated by d-isomerization of Ser14 and Ser7-relevant dimerization, allowing
      for the construction of a very potent HN derivative that was fully
      neuroprotective at 10 pM against 25 microM A beta1-43. This study provides
      important clues to the understanding of the neuroprotective mechanism of HN, as
      well as to the development of novel AD therapeutics.

PMID- 12787070
TI  - Functional consequences of homo- but not hetero-oligomerization between
      transporters for the biogenic amine neurotransmitters.
AB  - Before this study, the human norepinephrine transporter (hNET) was the only
      member of the biogenic amine neurotransmitter transporter family that had not
      been demonstrated to be a functional homo-oligomer. Here, using two forms of the
      transporter, I155C and hNET-myc, with distinct antigenicity and inhibitor
      sensitivity, we demonstrated that hNET exists as a homo-oligomer. hNET I155C is a
      functional mutant and is sensitive to inactivation by the sulfhydryl reagent [2
      (trimethylammonium)ethyl]methanethiosulfonate, while hNET-myc is resistant to
      inactivation by this reagent. Coimmunoprecipitation of these two forms
      demonstrated that a physical interaction exists between norepinephrine
      transporter monomers. Further characterization of this physical interaction has
      revealed that the activity of norepinephrine transporters depends on interactions
      between monomers. Because norepinephrine transporters and serotonin transporters
      are the only two members of the neurotransmitter transporter family endogenously
      expressed in the cell membrane of the same cells, placental syncytiotrophoblasts,
      we tested the ability of norepinephrine transporters and serotonin transporters
      to associate and function in a hetero-oligomeric form. Similarly, coexpression of
      hNET-myc with serotonin transporter-FLAG showed a physical interaction in
      coimmunoprecipitation assays. However, coexpression of serotonin and
      norepinephrine transporters did not sensitize norepinephrine transporter activity
      to inhibition by citalopram, a selective serotonin transport inhibitor. Thus, the
      norepinephrine transporter-serotonin transporter physical association did not
      produce functional consequences. Based on this, we propose that the transporters
      for biogenic amine neurotransmitters interact functionally in homo- but not
      hetero-oligomeric forms.

PMID- 12787072
TI  - Cystatin C colocalizes with amyloid-beta and coimmunoprecipitates with amyloid
      beta precursor protein in sporadic inclusion-body myositis muscles.
AB  - Cystatin C (CC), an endogenous cysteine protease inhibitor, is accumulated within
      amyloid-beta (A beta) amyloid deposits in Alzheimer's disease (AD) brain and was
      proposed to play a role in the AD pathogenesis. Because the chemo-morphologic
      muscle phenotype of sporadic inclusion-body myositis (s-IBM) has several
      similarities with the phenotype of AD brain, including abnormal accumulation of A
      beta deposits, we studied expression and localization of CC in muscle biopsies of
      10 s-IBM, and 16 disease- and five normal-control muscle biopsies. Physical
      interaction of CC with amyloid-beta precursor protein (A beta PP) was studied by
      a combined immunoprecipitation/immunoblotting technique in the s-IBM muscle
      biopsies and in A beta PP-overexpressing cultured human muscle fibers. In all s
      IBM muscle biopsies, CC-immunoreactivity either colocalized with, or was adjacent
      to, the A beta-immunoreactive inclusions in 80-90% of the vacuolated muscle
      fibers, mostly in non-vacuolated regions of their cytoplasm. Ultrastructurally,
      CC immunoreactivity-colocalized with A beta on 6-10 nm amyloid-like fibrils and
      floccular material. By immunoblotting, CC expression was strongly increased in
      IBM muscle as compared to the controls. By immunoprecipitation/immunoblotting
      experiments, CC coimmunoprecipitated with A beta PP, both in s-IBM muscle and in
      A beta PP-overexpressing cultured normal human muscle fibers. Our studies (i)
      demonstrate for the first time that CC physically associates with A beta PP, and
      (ii) suggest that CC may play a novel role in the s-IBM pathogenesis, possibly by
      influencing A beta PP processing and A beta deposition.

PMID- 12787073
TI  - Co-expression of non-selective cation channels of the transient receptor
      potential canonical family in central aminergic neurones.
AB  - The mammalian transient receptor potential canonical (TRPC) group of channels is
      a family of Ca2+-permeable cation channels that are activated following receptor
      mediated stimulation of different isoforms of phospholipase C. In vitro TRPC
      proteins can form hetero- or homo-oligomeric channels. We performed single-cell
      RT-PCR analysis to reveal the co-expression of seven TRPC channels in identified
      rat aminergic neurones. All serotonergic neurones of the dorsal raphe (DR), the
      majority of histaminergic (tuberomamillary nucleus; TMN) and dopaminergic cells
      of the ventral tegmental area (VTA), as well as some GABAergic neurones from the
      VTA, expressed at least one variant of TRPC channels. No TRPC channel expression
      was found in the locus coeruleus. In raphe neurones TRPC6 and TRPC5 mRNAs
      occurred most frequently. In VTA and TMN co-expression of TRPC4 with TRPC5 and
      TRPC6 with TRPC7 was not found in individual neurones (in contrast to the whole
      brain regions). Their co-expression in non-neuronal cells could not be excluded.
      The neonatal TRPC3 subunit was rarely seen. In DR, but not in the other nuclei
      studied, the expression of orexin receptors correlated with the expression of
      TRPC channels. We conclude that several TRPC channel populations exist in
      individual neurones and that their subunit co-expression pattern is region and
      cell-type specific.

PMID- 12787074
TI  - Chronic lithium administration potentiates brain arachidonic acid signaling at
      rest and during cholinergic activation in awake rats.
AB  - Studies were performed to determine if the reported 'proconvulsant' action of
      lithium in rats given cholinergic drugs is related to receptor-initiated
      phospholipase A2 signaling via arachidonic acid. Regional brain incorporation
      coefficients k* of intravenously injected [1-14C]arachidonic acid, which
      represent this signaling, were measured by quantitative autoradiography in
      unanesthetized rats at baseline and following administration of subconvulsant
      doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6
      weeks to produce a therapeutically relevant brain lithium concentration, the mean
      baseline values of k* in brain auditory and visual areas were significantly
      greater than in rats fed control diet. Arecoline at doses of 2 and 5 mg/kg
      intraperitoneally increased k* in widespread brain areas in rats fed the control
      diet as well as the LiCl diet. However, the arecoline-induced increments often
      were significantly greater in the LiCl-fed than in the control diet-fed rats.
      Lithium's elevation of baseline k* in auditory and visual regions may correspond
      to its ability in humans to increase auditory and visual evoked responses.
      Additionally, its augmentation of the k* responses to arecoline may underlie its
      reported 'proconvulsant' action with cholinergic drugs, as arachidonic acid and
      its eicosanoid metabolites can increase neuronal excitability and seizure
      propagation.

PMID- 12787075
TI  - Presenilin endoproteolysis mediated by an aspartyl protease activity
      pharmacologically distinct from gamma-secretase.
AB  - Presenilin (PS)-dependent gamma-secretase cleavage is the final proteolytic step
      in generating amyloid beta protein (A beta), a key peptide involved in the
      pathogenesis of Alzheimer's disease. PS undergoes endoproteolysis by an
      unidentified 'presenilinase' to generate the functional N-terminal and C-terminal
      fragment heterodimers (NTF/CTF) that may harbor the gamma-secretase active site.
      To better understand the relationship between presenilinase and gamma-secretase,
      we characterized the biochemical properties of presenilinase and compared them
      with those of gamma-secretase. Similar to gamma-secretase, presenilinase was most
      active at acidic pH 6.3. Aspartyl protease inhibitor pepstatin A blocked
      presenilinase activity with an IC50 of approximately 1 microM. Difluoroketone
      aspartyl protease transition state analogue MW167 was relatively selective for
      presenilinase (IC50 < 1 microM) over gamma-secretase (IC50-16 microM).
      Importantly, removing the transition state mimicking moiety simultaneously
      abolished both presenilinase and gamma-secretase inhibition, suggesting that
      presenilinase, like gamma-secretase, is an aspartyl protease. Interestingly,
      several of the most potent gamma-secretase inhibitors (IC50 = 0.3 or 20 nM)
      failed to block presenilinase activity. Although de novo generation of PS1
      fragments coincided with production of A beta in vitro, blocking presenilinase
      activity without reducing pre-existing fragment levels permitted normal de novo
      generation of A beta and amyloid intracellular domain. Therefore, presenilinase
      has characteristics of an aspartyl protease, but this activity is distinct from
      gamma-secretase.

PMID- 12787076
TI  - Susceptibility to kainate-induced seizures under dietary zinc deficiency.
AB  - Zinc homeostasis in the brain is altered by dietary zinc deficiency, and its
      alteration may be associated with the etiology and manifestation of epileptic
      seizures. In the present study, susceptibility to kainate-induced seizures was
      enhanced in mice fed a zinc-deficient diet for 4 weeks. When Timm's stain was
      performed to estimate zinc concentrations in synaptic vesicles, Timm's stain in
      the brain was attenuated in the zinc-deficient mice. In rats fed the zinc
      deficient diet for 4 weeks, susceptibility to kainate-induced seizures was also
      enhanced. When the release of zinc and neurotransmitters in the hippocampal
      extracellular fluid of the zinc-deficient rats was studied using in vivo
      microdialysis, the zinc concentration in the perfusate was less than 50% of that
      of the control rats and the increased levels of zinc by treatment with kainate
      were lower than the basal level in control rats, suggesting that vesicular zinc
      is responsive to dietary zinc deficiency. The levels of glutamate in the
      perfusate of the zinc-deficient rats were more increased than in the control
      rats, whereas the levels of GABA in the perfusate were not at all increased in
      the zinc-deficient rats, unlike in the control rats. The present results
      demonstrate an enhanced release of glutamate associated with a decrease in GABA
      concentrations as a possible mechanism for the increased seizure susceptibility
      under zinc deficiency.

PMID- 12787077
TI  - Truncated beta-amyloid peptide species in pre-clinical Alzheimer's disease as new
      targets for the vaccination approach.
AB  - Vaccination against human beta-amyloid peptide (A beta) has been shown to remove
      the amyloid burden produced in transgenic mice overexpressing the mutated human
      amyloid precursor protein (APP) gene. For human beings, the efficiency of this
      therapeutic strategy has to take into account the specificities of human amyloid,
      especially at the early stages of 'sporadic' Alzheimer's disease (AD). A beta
      40/42 were previously quantified in tissues from our well-established brain bank,
      including non-demented individuals with both mild amyloid and tau pathologies,
      hence corresponding to the earliest stages of Alzheimer pathology. Herein, we
      have adapted a proteomic method combined with western blotting and mass
      spectrometry for the characterization of insoluble A beta extracted in pure
      formic acid. We demonstrated that amino-truncated A beta species represented more
      than 60% of all A beta species, not only in full blown AD, but also, and more
      interestingly, at the earliest stage of Alzheimer pathology. At this stage, A
      beta oligomers were exclusively made of A beta-42 species, most of them being
      amino-truncated. Thus, our results strongly suggest that amino-truncated A beta
      42 species are instrumental in the amyloidosis process. In conclusion, a vaccine
      specifically targeting these pathological amino-truncated species of A beta-42
      are likely to be doubly beneficial, by inducing the production of specific
      antibodies against pathological A beta products that are, in addition, involved
      in the early and basic mechanisms of amyloidosis in humans.

PMID- 12787078
TI  - The Arg617-Arg618 cleavage site in the C-terminal domain of PC1 plays a major
      role in the processing and targeting of the enzyme within the regulated secretory
      pathway.
AB  - The C-terminal domain of the prohormone convertase PC1 is involved in targeting
      of the enzyme to secretory granules in neuroendocrine cells and is subsequently
      processed in this compartment at an Arg617-Arg618 site. Three other dibasics are
      found in the C-terminal domain of mouse PC1. Here, we examined the role of the
      four dibasics in targeting PC1 to secretory granules. All 15 possible
      combinations of dibasic mutations were performed. Wild-type (WT) and mutant PC1
      were stably expressed in neuroendocrine PC12 cells that lacked endogenous PC1.
      Processing, secretion and intracellular localization of PC1 and its mutants were
      analyzed. Leaving intact Arg617-Arg618 and mutating any combination of the three
      other dibasics yielded proteins that were stored and processed in secretory
      granules, similarly to WT PC1. Mutating Arg617-Arg618 alone or with any one of
      the three remaining dibasics generated proteins that were efficiently stored in
      secretory granules but were not processed further. Mutating Arg617-Arg618 with
      more than one of the remaining dibasics produced proteins that reached the TGN
      but were not stored in secretory granules and exited the cells through the
      constitutive secretory pathway. These data demonstrate that the Arg617-Arg618
      plays a prominent role in targeting PC1 to secretory granules.

PMID- 12787079
TI  - Molecular neuroadaptations in the accumbens and ventral tegmental area during the
      first 90 days of forced abstinence from cocaine self-administration in rats.
AB  - Cocaine self-administration is associated with a propensity to relapse in humans
      and reinstatement of drug seeking in rats after prolonged withdrawal periods.
      These behaviors are hypothesized to be mediated by molecular neuroadaptations
      within the mesolimbic dopamine system. However, in most studies of drug-induced
      neuroadaptations, cocaine was experimenter-delivered and molecular measurements
      were performed after short withdrawal periods. In the present study, rats were
      trained to self-administer intravenous cocaine or oral sucrose (a control non
      drug reward) for 10 days (6-h/day) and were killed following 1, 30, or 90 days of
      reward withdrawal. Tissues from the accumbens and ventral tegmental area (VTA)
      were assayed for candidate molecular neuroadaptations, including enzyme
      activities of cAMP-dependent protein kinase (PKA) and adenylate cyclase (AC), and
      protein expression of cyclin-dependent kinase 5 (cdk5), tyrosine hydroxylase (TH)
      and glutamate receptor subunits (GluR1, GluR2 and NMDAR1). In the accumbens of
      cocaine-trained rats, GluR1 and NMDAR1 levels were increased on days 1 and 90,
      while GluR2 levels were increased on days 1 and 30, but not day 90; PKA activity
      levels were increased on days 1 and 30, but not day 90, while AC activity, TH and
      cdk5 levels were unaltered. In the VTA of cocaine-trained rats, NMDAR1 levels
      were increased for up to 90 days, while GluR2 levels were increased only on day
      1; TH and Cdk5 levels were increased only on day 1, while PKA and AC activity
      levels were unaltered. Cocaine self-administration produces long-lasting
      molecular neuroadaptations in the VTA and accumbens that may underlie cocaine
      relapse during periods of abstinence.

PMID- 12787083
TI  - Numerical studies of optical switching and optical bistability phenomena of nano-
      or meso-size spheres.
AB  - We propose the use of numerical calculations of the optical response of nonlinear
      Kerr-spheres, modifying the Mie theory. As a numerical example, we use a CuCl
      sphere coated with a Kerr-nonlinear sphere, taking into account the excitation of
      the Z3-exciton. The results clearly show that optical bistable and/or optical
      switching devices can be realized on a nano- and meso-size scale when the real
      part of the dielectric constant of CuCl is negative.

PMID- 12787080
TI  - Post-transcriptional suppression of pathogenic prion protein expression in
      Drosophila neurons.
AB  - A wealth of evidence supports the view that conformational change of the prion
      protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic,
      infectious, and inherited forms of prion disease. Although the central role
      played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular
      mechanisms that recognize PrPSc and modulate its production, clearance, and
      neural toxicity have not been elucidated. To address these questions, we used a
      tissue-specific expression system to express wild-type and disease-associated PrP
      molecules heterologously in Drosophila melanogaster. Our results indicate that
      Drosophila brain possesses a specific and saturable mechanism that suppresses the
      accumulation of PG14, a disease-associated insertional PrP mutant. We also found
      that wild-type PrP molecules are maintained in a detergent-soluble conformation
      throughout life in Drosophila brain neurons, whereas they become detergent
      insoluble in retinal cells as flies age. PG14 protein expression in Drosophila
      eye did not cause retinal pathology. Our work reveals the presence of mechanisms
      in neurons that specifically counterbalance the production of misfolded PrP
      conformations, and provides an opportunity to study these processes in a model
      organism amenable to genetic analysis.

PMID- 12787084
TI  - Upconversion fluorescence imaging of erbium-doped fluoride glass particles by
      apertureless SNOM.
AB  - We have imaged fluorescent erbium-doped fluoride glass particles by apertureless
      scanning near-field optical microscopy. The optical excitation has been performed
      at lambda = 780 nm whereas fluorescence emission has been collected around lambda
      = 550 nm. This process, called upconversion by energy transfer, involves two
      erbium ions and is not linear. Besides an improvement of the lateral resolution,
      we have observed on some particles that the fluorescence is not homogeneously
      distributed, but is rather localized in some zones brighter than others. By
      making tip approach curves, we have also observed that the amount of fluorescence
      intensity scattered by the tip is increasing when the tip is approaching the
      sample surface.

PMID- 12787085
TI  - Probing highly confined optical fields in the focal region of a high NA parabolic
      mirror with subwavelength spatial resolution.
AB  - Parabolic mirrors with a high numerical aperture can be conveniently used to
      produce highly confined optical fields in the focal region. Furthermore, these
      fields can have interesting polarization behaviour due to the high numerical
      aperture. In particular, if the mirror is illuminated with a size matched
      radially polarized or azimuthally polarized doughnut mode, the electric field has
      in the focal region almost exclusively a longitudinal or a transverse
      polarization component. Such field distributions are interesting for applications
      in confocal or near-field optical microscopy. Here we present experimental
      results where we have probed some of these field distributions by raster scanning
      a fine gold tip in nanometer steps through the focal region and detecting the
      scattered light intensity. The measured intensity patterns are compared with
      corresponding vector-field calculations.

PMID- 12787086
TI  - Magneto-optical near-field microscopy of ultrathin films in ultrahigh vacuum.
AB  - We demonstrate that magnetic domains of ultrathin films can be imaged in situ in
      ultrahigh vacuum (UHV) by scanning near-field optical microscopy in combination
      with a Sagnac interferometer (Sagnac-SNOM). In the present set-up, the Sagnac
      interferometer is not only used for measuring the magneto-optical Kerr effect but
      also for tip-to-sample distance control. The high sensitivity of the instrument
      enabled us to study the magnetization reversal processes in externally applied
      magnetic fields in ultrathin films of Fe and Ni grown on Cu(100) single crystals.

PMID- 12787087
TI  - Near-field nano-ellipsometer for ultrathin film characterization.
AB  - We describe a near-field ellipsometer for accurate characterization of ultrathin
      dielectric films. Optical tunnelling mimics the absorption in metallic films,
      enabling accurate measurement of the refractive index of ultrathin dielectric
      film. A regression model shows that a refractive index resolution of 0.001 for
      films as thin as 1 nm is possible. A solid-immersion nano-ellipsometer that
      incorporates this near-field ellipsometric technique with a solid-immersion lens
      is constructed to demonstrate the viability of this technique. Such a nano
      ellipsometer can accurately characterize thin films ranging in thickness from
      subnanometre to micrometres with potential transverse resolution of the order of
      100 nm.

PMID- 12787088
TI  - Plasmon-coupled tip-enhanced near-field optical microscopy.
AB  - Near the cut-off radius of a guided waveguide mode of a metal-coated glass fibre
      tip it is possible to couple radiation to surface plasmons propagating on the
      outside surface of the metal coating. These surface plasmons converge toward the
      apex of the tip and interfere constructively for particular polarization states
      of the initial waveguide mode. Calculations show that a radially polarized
      waveguide mode can create a strong field enhancement localized at the apex of the
      tip. The highly localized enhanced field forms a nanoscale optical near-field
      source.

PMID- 12787089
TI  - Study of the focused laser spots generated by various polarized laser beam
      conditions.
AB  - In this work, three-dimensional near-field imaging of the focused laser spot was
      studied theoretically and experimentally. In the theoretical simulation, we use
      the electromagnetic equivalent of the vectorial Kirchhoff diffraction integral to
      calculate the intensity distribution of the focal region, and a high
      depolarization is found in high numerical aperture systems (NA = 0.85). The
      experimental set-up is based on a near-field scanning optical microscope (NSOM)
      system. A high-NA objective lens is used to focus incident light of various
      polarizations, and a tapered near-field optical fibre probe of the NSOM system is
      used to determine the intensity of the focal field. The results show an
      asymmetric distribution of the focused intensity with the linear polarized laser
      beam.

PMID- 12787090
TI  - Optical switching due to whispering gallery modes in dielectric microspheres
      coated by a Kerr material.
AB  - We numerically evaluated the optical responses of a nonlinear microsphere put on
      prisms, i.e. in prism-coupling geometry where the incident light excites the WGM
      through near-field coupling. As numerical calculations, we employed the finite
      difference time-domain method taking into account Kerr nonlinearity. The sphere
      was coated by a Kerr material with 160 nm thick. The third-order nonlinear
      susceptibility of the Kerr material chi(3) was assumed to be 7 x 10(-14)[m(2) V(
      2)]. The diameter of the sphere was assumed to be 1 micro m. The numerical
      results have shown that the control and/or the signal lights can induce the
      optical switching-like variation in the reflectance. Such a nonlinear response of
      the sphere has been interpreted by the variation in the dielectric constant of
      the sphere due to a Kerr nonlinearity.

PMID- 12787091
TI  - Near-field Raman spectroscopy using a sharp metal tip.
AB  - Near-field Raman spectroscopy with a spatial resolution of 20 nm is demonstrated
      by raster scanning a sharp metal tip over the sample surface. The method is used
      to image vibrational modes of single-walled carbon nanotubes. By combining
      optical and topographical signals rendered by the single-walled carbon nanotubes,
      we can separate near-field and far-field contributions and quantify the observed
      Raman enhancement factors.

PMID- 12787092
TI  - Current-sensing scanning near-field optical microscopy using a metal probe for
      nanometre-scale observation of electrochromic films.
AB  - A novel technique for scanning near-field optical microscopy capable of point
      contact current-sensing was developed in order to investigate the nanometre-scale
      optical and electrical properties of electrochromic materials. An apertureless
      bent-metal probe was fabricated in order to detect optical and current signals at
      a local point on the electrochromic films. The near-field optical properties
      could be observed using the local field enhancement effect generated at the edge
      of the metal probe under p-polarized laser illumination. With regard to
      electrical properties, current signal could be detected with the metal probe
      connected to a high-sensitive current amplifier. Using the current-sensing
      scanning near-field optical microscopy, the surface topography, optical and
      current images of coloured WO3 thin films were observed simultaneously.
      Furthermore, nanometre-scale electrochromic modification of local bleaching could
      be performed using the current-sensing scanning near-field optical microscopy.
      The current-sensing scanning near-field optical microscopy has potential use in
      various fields of nanometre-scale optoelectronics.

PMID- 12787093
TI  - Excitation dynamics in a three-quantum dot system driven by optical near-field
      interaction: towards a nanometric photonic device.
AB  - Using density operator formalism, we discuss interdot excitation energy transfer
      dynamics driven by the optical near-field and phonon bath reservoir, as well as
      coherent excitation dynamics of a quantum dot system. As an effective interaction
      between quantum dots induced by the optical near-field, the projection operator
      method gives a renormalized dipole interaction, which is expressed as a sum of
      the Yukawa functions and is used as the optical near-field coupling of quantum
      dots. We examine one- and two-exciton dynamics of a three-quantum dot system
      suggesting a nanometric photonic switch, and numerically obtain a transfer time
      comparable with the recent experimental results for CuCl quantum dots.

PMID- 12787094
TI  - The effects of probe boundary conditions and propagation on nano-Raman
      spectroscopy.
AB  - Raman spectra obtained in the near-field, with collection of the Raman-shifted
      light in reflection, show selective enhancement of vibrational modes. We show
      that the boundary conditions for an electric field near a metal surface affect
      propagation of the reflected signal and lead to this selection. The enhancement
      of certain Raman forbidden vibrations is explained by the presence of an electric
      field gradient near the metal-apertured fibre probe.

PMID- 12787095
TI  - Electrodynamic interaction between two atoms in near-field contact.
AB  - A theoretical study of elements of the quantum electrodynamic interaction between
      two single-electron atoms in near-field contact is presented. The framework of
      the study is an electromagnetic propagator formalism that allows one to describe
      the near-field space-time interaction in such a manner that the Einstein
      causality and lack of photon localizability are manifest. First we set up the
      atom-field Hamiltonian in the so-called G-gauge, starting from the Coulomb
      Hamiltonian, and thereafter we show that this leads to a correct propagator
      description for the retarded part of the transverse electromagnetic field
      (operator). In the G-gauge approach, renormalization of the two-particle energy
      level structure stemming from the transverse self-field occurs. The intraparticle
      renormalization is calculated for a three-level atom (it is trivial for a two
      level atom), and the interparticle renormalization, which depends on the atomic
      separation, is determined for two two-level atoms. The magnitude of the energy
      renormalization is always finite in our theory because we do not consider the
      atoms to be point-like objects from an electromagnetic point of view. Throughout,
      we relate our G-gauge formalism to the multipole theory often used in studies of
      interatomic electrodynamics.

PMID- 12787096
TI  - A versatile multipurpose scanning probe microscope.
AB  - A combined scanning probe microscope has been developed that allows simultaneous
      operation as a non-contact/tapping mode atomic force microscope, a scattering
      near-field optical microscope, and a scanning tunnelling microscope on conductive
      samples. The instrument is based on a commercial optical microscope. It operates
      with etched tungsten tips and exploits a tuning fork detection system for
      tip/sample distance control. The system has been tested on a p-doped silicon
      substrate with aluminium depositions, being able to discriminate the two
      materials by the electrical and optical images with a lateral resolution of 130
      nm.

PMID- 12787097
TI  - Large-area topography analysis and near-field Raman spectroscopy using bent fibre
      probes.
AB  - We present a method for combined far-field Raman imaging, topography analysis and
      near-field spectroscopy. Surface-enhanced Raman spectra of Rhodamine 6G (R6G)
      deposited on silver nanoparticles were recorded using a bent fibre aperture-type
      near-field scanning optical microscope (NSOM) operated in illumination mode.
      Special measures were taken to enable optical normal-force detection for control
      of the tip-sample distance. Comparisons between far-field Raman images of R6G
      covered Ag particle aggregates with topographic images recorded using atomic
      force microscopy (AFM) indicate saturation effects due to resonance excitation.

PMID- 12787098
TI  - Scanning near-field optical microscopy using semiconductor nanocrystals as a
      local fluorescence and fluorescence resonance energy transfer source.
AB  - Local fluorescence probes based on CdSe semiconductor nanocrystals were prepared
      and tested by recording scanning near-field optical microscopy (SNOM) images of
      calibration samples and fluorescence resonance energy transfer SNOM (FRET SNOM)
      images of acceptor dye molecules inhomogeneously deposited onto a glass
      substrate. Thousands of nanocrystals contribute to the signal when this probe is
      used as a local fluorescence source while only tens of those (the most apical)
      are involved in imaging for the FRET SNOM operation mode. The dip-coating method
      used to make the probe enables diminishing the number of active fluorescent
      nanocrystals easily. Prospects to realize FRET SNOM based on a single
      fluorescence centre using such an approach are briefly described.

PMID- 12787099
TI  - Near-field radiation of bow-tie antennas and apertures at optical frequencies.
AB  - We investigate the ability of the bow-tie slot antenna to generate intense
      optical spots below the diffraction limit. A commercially available finite
      difference time-domain electromagnetic modelling software is used in the
      numerical simulations. The finite-difference time-domain software is first
      compared to analytical results at optical frequencies to verify its accuracy. We
      then present numerical simulations for various geometries involving apertures on
      thin films and the bow-tie antenna. The transmission efficiency and optical spot
      size of the bow-tie antenna are compared with those of rectangular and circular
      apertures on thin metal films. We also investigate the effects of material
      composition, frequency, and antenna geometry on the near-field radiation pattern
      using numerical simulations.

PMID- 12787100
TI  - Propagation of surface plasmon polariton in nanometre-sized metal-clad optical
      waveguides.
AB  - Using a local anodic-oxidation method with a probe tip of a scanning near-field
      optical microscope (SNOM) as the electrode, we have fabricated an oxide core with
      subwavelength dimensions on metal. The propagation of the surface plasmon
      polariton (SPP), which is excited at the interface between the oxide core and the
      metal clad, has been investigated using the same SNOM. Altering the wavelength of
      input light from 532 nm to 830 nm, the propagation length of the SPP extends from
      2 micro m to 6 micro m. We carried out a simulation of the SPP propagation, and
      obtained a similar wavelength dependence.

PMID- 12787101
TI  - Scanning near-field optical microscopy of a cell membrane in liquid.
AB  - The applications of scanning near-field optical microscopy to biological
      specimens under physiological conditions have so far been very rare since common
      techniques for a probe-sample distance control are not as well suited for
      operation in liquid as under ambient conditions. We have shown previously that
      our own approach for a distance control, based on a short aperture fibre probe
      and a tuning fork as force sensor in a tapping mode, works well even on soft
      material in water. By means of an electronic self-excitation circuit, which
      compensates for changes of the resonance frequency due to evaporation of liquid,
      the stability of the force feedback has now been further improved. We present
      further evidence for the excellent suitability of the tapping-mode-like distance
      control to an operation in liquid, for example, by force-imaging of double
      stranded DNA. Moreover, we demonstrate that a nuclear envelope in liquid can be
      imaged with a high optical resolution of approximately 70 nm without affecting
      its structural integrity. Thereby, single nuclear pores in the nuclear envelope
      with a nearest neighbour distance of approximately 120 nm have been optically
      resolved for the first time.

PMID- 12787102
TI  - Simulation of an aperture in the thick metallic screen that gives high intensity
      and small spot size using surface plasmon polariton.
AB  - The optical wave behaviour around a subwavelength aperture in a thick metallic
      screen is examined through three-dimensional computer simulation. Treating the
      metallic screen as a dielectric slab with complex-valued permittivity, it is
      possible to design an aperture that simultaneously provides high intensity and
      small spot size through the excitation of surface plasmon polaritons on the side
      walls of the aperture.

PMID- 12787103
TI  - A method for controlling the spins of atoms using optical near-fields.
AB  - On the basis of the procedure for controlling the spins of atoms using circularly
      polarized evanescent light proposed by Hori et al.[(1996) Abstracts of the 1st
      Asia-Pacific Workshop on Near-field Optics] we discuss the influence of boundary
      conditions on the probability of spontaneous emission and thus on the spin
      polarization efficiency, which was not considered in the Hori et al. study. Using
      the Carniglia-Mandel mode expansion of electromagnetic fields, we derive the
      spontaneous emission and spin polarization probabilities of atoms near a
      dielectric surface, and show the atom-surface distance dependence and refractive
      index dependence. Numerical evaluation for the 6P1/2-6S1/2 transition of a Cs
      atom indicates an increase in the efficiency of spin polarization by 30%.

PMID- 12787104
TI  - Transient optical elements: application to near-field microscopy.
AB  - We report methods of near-field infrared microscopy with transient optically
      induced probes. The first technique - a transient aperture (TA) - uses
      photoinduced reflectivity in semiconductors to generate a relatively large
      transient mirror (TM) with a small aperture at its centre. We report the optical
      properties of the TM and TA and experiments performed on near-field imaging with
      the TA. The second technique is based on solid immersion microscopy, in which
      high resolution is achieved when light is focused inside a solid with a high
      refractive index. By creating a transient Fresnel lens on the surface of a
      semiconductor wafer via photoinduction, we were able to form a solid immersion
      lens (SIL) for use as a near-field probe. The use of transient probes eliminates
      the need for mechanical scanning of the lens or sample, and thus provides a much
      faster scanning rate and the possibility to work with soft and liquid objects.

PMID- 12787105
TI  - Performance of visible and mid-infrared scattering-type near-field optical
      microscopes.
AB  - We describe the principles of two scattering-type near-field optical microscopes
      (s-SNOMs), one operating at 633 nm wavelength, the other at selectable
      wavelengths in the range 7.3-11.3 micro m, and compare the measurement
      experience. Both use interferometric detection of scattered radiation, and are
      therefore capable of amplitude and phase-contrast imaging. In this study both
      instruments use the same or even identical commercial probe tips, and measure a
      single, three-component, test sample. Our results show that the imaging process
      of s-SNOM is wavelength-independent, namely, that the resolution is determined by
      the properties of the tip only, and that the contrast is given by the complex
      refractive index of the sample, predictable from a simple, analytical model of
      tip-sample interaction. A novel, 'edge-darkening' artefact is described which may
      appear in s-SNOM and that is wavelength-independent.

PMID- 12787106
TI  - Near-field observation of carrier diffusion in GaAs quantum structures under high
      magnetic fields.
AB  - Photoluminescence from a two-dimensional electron-gas system in GaAs single
      hetero-structures was investigated using a scanning near-field optical microscope
      (SNOM) operated at cryogenic temperatures under high magnetic fields. The local
      intensity of the luminescence increased 600-fold that at 0 T as the magnetic
      field was increased up to 6 T. The enhancement depended on the spatial resolution
      of the SNOM. These characteristics are explained by the suppression of the
      diffusion of photocarriers caused by the Lorentz force in magnetic fields.

PMID- 12787107
TI  - Bessel beams as virtual tips for near-field optics.
AB  - In the previous NFO meeting, we proposed the use of confined evanescent light
      beams as 'virtual' or 'immaterial' tips. Unfortunately, this technique was
      hindered by the need for perfectly radially polarized light beams. In this
      communication, we propose a simple, stable and cheap method allowing the
      generation of beams of any polarization and more especially of purely radially
      polarized light beams. We also demonstrate both theoretically and experimentally
      that for near-field imaging systems polarization is a limiting factor of
      resolution and light confinement. Finally, we present the very first experimental
      results dealing with virtual tips.

PMID- 12787108
TI  - Experimental studies of surface plasmon polariton band gap effect.
AB  - Surface plasmon polaritons (SPPs) propagation at a gold film surface covered by
      periodic arrays of approximately 40-nm-high scatterers arranged in a triangular
      lattice of different periods containing straight line defects is studied using
      collection scanning near-field optical microscopy. The results reveal the
      dependence of the SPP band gap (SPPBG) effect manifested via the SPP reflection
      and guiding (along line defects) on the parameters of the surface structures
      (period, filling factor and lattice orientation). We find that the SPPBG effect
      is stronger along GammaK direction for all investigated periodic structures. Our
      results demonstrate that the SPPBG effect becomes less pronounced with a decrease
      of the filling factor and disappears for a filling factor close to 0.2. We also
      observe that the centre of the SPPBG shifts towards longer wavelengths with an
      increase of the lattice period.

PMID- 12787109
TI  - Apertureless near-field Raman spectroscopy.
AB  - We report on the tip-enhanced Raman spectra of C60 obtained on a custom-built
      apertureless scanning near-field optical microscope. A commercial atomic force
      microscope tip coated with 100 nm thickness of gold was used to enhance locally
      the Raman signal and permit topographic and spectral information to be acquired
      simultaneously. We present preliminary data which demonstrate the tip enhancement
      effect using C60 as a test sample.

PMID- 12787110
TI  - Systematic variation of polymer jacketed fibres and the effects on tip etching
      dynamics.
AB  - Using a chemically etched fibre probe through a plastic jacket provides a simple
      way to smooth a tip's surface. Convection flow in the plastic tube and lateral
      diffusion with fixed meniscus height has been proposed to explain such
      improvement. Fibres with additive thin polymer layers and bare fibres with thick
      untapered/tapered plastic layers have been prepared to verify the dominant
      mechanism. The additive layers greatly change the tip's geometry and bare-fibres
      with untapered plastics cannot form tips. This confirmed that lateral diffusion
      dominates the etching process. Based on our investigation, we propose a new non
      meniscus end-etching method by using tapered plastics. Unlike etching methods
      with meniscus, the end-etching method can regularly form very smooth tips. It is
      insensitive to vibrations and temperature drifts and also suitable for most
      fibres.

PMID- 12787111
TI  - Photo-initiated energy transfer in nanostructured complexes observed by near
      field optical microscopy.
AB  - We report an apertureless near-field optical study on nanostructured objects
      formed by J-aggregates adsorbed on silver (Ag) nanoparticles. Near-field images
      reveal that the enhanced near-field from the dressed particle's (DP) resonantly
      excited plasmon oscillation is efficiently absorbed by the J-aggregates. The
      sensitivity of the near-field images recorded at the harmonics of the probe
      vibration frequency suggests that the DP is releasing part of the absorbed energy
      radiatively upon interaction with the probe. The role of the probe in providing
      this new radiative relaxation channel is further confirmed as fluorescence from
      the J-aggregates on the particle is detected on the particle location only. We
      based the interpretation of our results on the near-field optical response from a
      bare Ag particle excited at the plasmon resonance as well as on far-field
      emission and transient absorption experiments.

PMID- 12787112
TI  - How light gets through periodically nanostructured metal films: a role of surface
      polaritonic crystals.
AB  - The physical origin of the enhanced optical transmission of periodically
      structured films related to surface plasmon polaritons is discussed from first
      principles. The enhancement of transmission through smooth, randomly rough and
      periodically nanostructured films is considered. Analysis shows that any metal
      (or dielectric) nanostructured film can exhibit enhanced transmission in certain
      spectral ranges corresponding to surface plasmon (or phonon) polariton Bloch mode
      states on a periodic structure. Resonant tunnelling via these states is
      responsible for the transmission enhancement. The properties of surface
      polaritonic crystals are analogous to those of photonic crystals and can find
      numerous applications for scaling down optical devices to nanometric dimensions
      as well as for designing novel nanostructured materials whose optical properties
      are determined by surface polariton interaction in a periodic structure.

PMID- 12787113
TI  - Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications
      for hair growth control.
AB  - The continuously remodeled hair follicle is a uniquely exploitable epithelial
      mesenchymal interaction system. In contrast to the cyclical fate of the hair
      follicle epithelium, the dynamics of the supposedly stable hair follicle
      mesenchyme remains enigmatic. Here we address this issue using the C57BL/6 hair
      research model. During hair growth, increase in total follicular papilla size was
      associated with doubling of papilla cell numbers, much of which occurred before
      intra-follicular papilla cell proliferation, and subsequent to mitosis in the
      proximal connective tissue sheath. This indicates that some papilla cells
      originate in, and migrate from, the proliferating pool of connective tissue
      sheath fibroblasts. Follicular papilla cell number and total papilla size were
      maximal by anagen VI, but intriguingly, decreased by 25% during this period of
      sustained hair production. This cell loss, which continued during catagen, was
      not associated with intra-follicular papilla apoptosis, strongly indicating that
      fibroblasts migrate out of the late anagen/early catagen papilla and re-enter the
      proximal connective tissue sheath. Low-level apoptosis occurred only here, along
      with the "detachment" of cells from the regressing connective tissue sheath.
      Thus, the hair follicle mesenchyme exhibits significant hair cycle-associated
      plasticity. Modulation of these cell interchanges is likely to be important
      during clinically important hair follicle transformations, e.g. vellus-to
      terminal and terminal-to-vellus during androgenetic alopecia.

PMID- 12787115
TI  - Ultraviolet a induces generation of squalene monohydroperoxide isomers in human
      sebum and skin surface lipids in vitro and in vivo.
AB  - At the outermost surface of human skin, skin surface lipids are first-line
      targets of solar ultraviolet radiation. Therefore, we hypothesized that
      ultraviolet A and ultraviolet B irradiation induce photo-oxidation of skin
      surface lipids. To test this, sebum samples were collected from facial skin of 17
      healthy volunteers, weighed, and immediately irradiated with either ultraviolet B
      or ultraviolet A. Squalene, the major sebum lipid, as well as photo-oxidation
      products were identified in sebum lipid extracts by high-performance liquid
      chromatography analysis. Upon ultraviolet A exposures squalene was depleted in a
      concentration-dependent manner, whereas an unidentified sebum lipid photo
      oxidation product was detected. Using high-performance thin layer chromatography,
      high-performance liquid chromatography, atmospheric pressure chemical ionization
      mass spectrometry, and nuclear magnetic resonance, unidentified sebum lipid photo
      oxidation product was identified as a mixture of squalene monohydroperoxide
      isomers. Squalene monohydroperoxide isomers purified from sebum were identical
      with squalene monohydroperoxide isomers synthesized by preparative photo
      oxidation of squalene. Squalene monohydroperoxide isomers were formed even after
      small suberythematogenic doses of ultraviolet A (5 J per cm2). Whereas
      physiologic baseline levels of squalene monohydroperoxide isomers in human skin
      were only slightly above detection limits, squalene monohydroperoxide isomer
      levels were strongly increased by suberythematogenic doses of ultraviolet A both
      in vitro and in vivo. High-performance liquid chromatography results could be
      complemented by a straightforward thin layer chromatography method for rapid
      screening of lipid peroxide formation in human sebum/skin surface lipids. In
      conclusion, specific squalene monohydroperoxide isomers were identified as highly
      ultraviolet A sensitive skin surface lipid breakdown products that may serve as a
      marker for photo-oxidative stress in vitro and in vivo.

PMID- 12787114
TI  - Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are
      expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line
      (SEB-1).
AB  - Although the human sebaceous gland can synthesize cholesterol from acetate and
      can further metabolize steroids such as dehydroepiandrosterone into potent
      androgens, the de novo production of steroids from cholesterol has not been
      demonstrated in human skin. The goal of this study was to delineate the
      steroidogenic pathway upstream from dehydroepiandrosterone by documenting the
      presence of members of the P450 side chain cleavage system (P450scc). This system
      catalyzes the initial step in steroid hormone synthesis following translocation
      of cholesterol to the inner mitochondrial membrane. In concert with its
      cofactors, adrenodoxin and adrenodoxin reductase, and the transcription factor
      steroidogenic factor 1, P450scc converts cholesterol to pregnenolone. An SV40
      immortalized human sebaceous gland cell line (SEB-1) was established in order to
      facilitate investigation of the P450scc system. The sebaceous phenotype of SEB-1
      sebocytes was confirmed using immunohistochemistry, Oil Red O staining, and gene
      array expression analysis. Presence of P450scc, adrenodoxin reductase, cytochrome
      P450 17-hydroxylase (P450c17), and steroidogenic factor 1 was documented in human
      facial skin, human sebocytes, and SEB-1 sebocytes. Using immunohistochemistry,
      antibodies to the above proteins localized to epidermis, hair follicles,
      sebaceous ducts, and sebaceous glands in sections of facial skin. Results of
      immunohistochemistry were confirmed with Western blotting. Biochemical activity
      of cytochrome P450scc and P450c17 was demonstrated in SEB-1 sebocytes using
      radioimmunoassay. The relative abundance of mRNA for P450scc, P450c17, and
      steroidogenic factor 1 in SEB-1 sebocytes and sebaceous glands was compared to
      mRNA levels in ovarian theca and granulosa cells using real-time quantitative
      polymerase chain reaction. Gene array expression analysis and quantitative
      polymerase chain reaction indicated that mRNA for P450scc is more abundant than
      mRNA for both P450c17 and steroidogenic factor 1 in sebaceous glands and SEB-1
      cells. These data demonstrate that the skin is in fact a steroidogenic tissue.
      The clinical significance of this finding in mediating androgenic skin disorders
      such as acne, hirsutism, or androgenetic alopecia remains to be established.

PMID- 12787117
TI  - Measuring atopic dermatitis severity in randomized controlled clinical trials:
      what exactly are we measuring?
AB  - Well-designed clinical trials are a fundamental aspect of evidence-based
      medicine. Such trials are dependent on the use of valid, reliable, and relevant
      outcome measures. Wide variation in outcome methodology can have important
      detrimental effects on the correct interpretation and comparison of results. The
      objective of this study was to describe the variation in outcome methodology in
      randomized controlled trials of therapeutic interventions for atopic dermatitis
      published between January 1994 and December 2001. Of the 93 eligible randomized
      controlled trials identified using a systematic electronic database search
      strategy, 85 (91%) incorporated an objective measurement of clinical signs. Only
      23 (27%) of these trials used a published severity scale, however. The remainder
      used either modified versions of published scales (14%) or unnamed scales with no
      data on validity or reliability (59%), although unpublished scales were used
      significantly less frequently over the last 2 y compared to previously (21%vs
      74%, p<0.01). There was lack of consensus on which clinical features best reflect
      disease severity, with 31 different descriptions of clinical signs being used
      across all scoring systems. Fifty-six different "objective" clinical scales were
      identified. Patient symptoms were recorded in 80 trials (86%) and disease extent
      in 62 trials (67%). Quality of life was measured in only three trials (3%). This
      wide variation in outcome methodology is hindering evidence-based practice, and
      the widespread use of unvalidated outcome measures is a potential source of bias
      and inaccuracy. More emphasis should be placed on measuring things that are
      important to patients such as symptoms and quality of life.

PMID- 12787116
TI  - Analysis of microenvironmental factors contributing to basement membrane assembly
      and normalized epidermal phenotype.
AB  - To understand further the role of the dynamic interplay between keratinocytes and
      stromal components in the regulation of the growth, differentiation,
      morphogenesis, and basement membrane assembly of human stratified squamous
      epithelium, we have generated novel, three-dimensional organotypic cultures in
      which skin keratinocytes were grown in the absence or presence of pre-existing
      basement membrane components and/or dermal fibroblasts. We found that
      keratinocytes cultured in the presence of pre-existing basement membrane
      components and dermal fibroblasts for 9 d showed rapid assembly of basement
      membrane, as seen by a nearly complete lamina densa, hemidesmosomes, and the
      polarized, linear distribution of laminin 5 and a6 integrin subunit. Basement
      membrane assembly was somewhat delayed in the absence of dermal fibroblasts, but
      did occur at discrete nucleation sites when pre-existing basement membrane
      components were present. No basement membrane developed in the absence of pre
      existing basement membrane components, even in the presence of dermal
      fibroblasts. Bromodeoxyuridine incorporation studies showed that early
      keratinocyte growth was independent of mesenchymal support, but by 14 d, both
      fibroblasts and assembled basement membrane were required to sustain growth.
      Normalization of keratinocyte differentiation was independent of both dermal
      fibroblasts and structured basement membrane. These results indicated that
      epithelial and mesenchymal components play a coordinated role in the generation
      of structured basement membrane and in the regulation of normalized epithelial
      growth and tissue architecture in an in vitro model of human skin.

PMID- 12787118
TI  - Identification of COL7A1 alternative splicing inserting 9 amino acid residues
      into the fibronectin type III linker domain.
AB  - Type VII collagen is the major component of anchoring fibrils within the
      cutaneous basement membrane zone. The large amino-terminal noncollagenous domain
      of type VII collagen interacts with various extracellular matrix proteins and
      contributes to the dermal-epidermal attachment. The purpose of this study was to
      detect alternative splicing of COL7A1 transcript encoding the noncollagenous 1
      domain. The alternative splicing in this region may affect interactions of the
      noncollagenous 1 domain with extracellular matrix proteins and also dermal
      epidermal adhesion. Thus we examined expression of the alternative splicing in
      situations relating to wound healing and skin remodeling that required dermal
      epidermal binding and detachment. Amplification of overlapping cDNA from
      keratinocytes using reverse transcription-polymerase chain reaction identified
      alternative splicing, which was generated by a different exon 18 acceptor site 27
      bp upstream from the common acceptor site. Expression of this alternatively
      spliced transcript differed among several cell types. The nine amino acid
      residues GPLTLPLSP from the 27 bp nucleotides were inserted into the linker of
      fibronectin type III domains. This insertion was suggested to contribute to
      flexibility of the linker of fibronectin type III domains and may affect the
      interactions between the noncollagenous 1 domain and extracellular matrix
      proteins. Treatment with transforming growth factor-beta 1, which is known to
      promote wound healing and skin remodeling, enhanced the expression of this 27 bp
      transcript. Furthermore, keratinocyte biopsies from the wound edge of patients
      with epithelizing skin ulcers showed a significant increase in the 27 bp
      transcript expression compared with normal keratinocytes from steady-state body
      sites. These results suggest that amino acid variation of this alternative
      splicing may have some role in dermal-epidermal adhesion, wound healing, and skin
      remodeling. To the best of our knowledge, this is the first evidence of
      alternative splice insertion of a small peptide into the linker region of the
      fibronectin type III domains, a common motif within modular proteins.

PMID- 12787119
TI  - SPARC-null mice display abnormalities in the dermis characterized by decreased
      collagen fibril diameter and reduced tensile strength.
AB  - Although collagen and elastic fibers are among the major structural constituents
      responsible for the mechanical properties of skin, proteins that associate with
      these components are also important for directing formation and maintaining the
      stability of these fibers. We present evidence that SPARC (secreted protein
      acidic and rich in cysteine) contributes to collagen fibril formation in the
      dermis. The skin of SPARC-null adult mice had approximately half the tensile
      strength as that of wild-type skin. Moreover, the collagen content of SPARC-null
      skin, as measured by hydroxyproline analysis, was substantially reduced in adult
      mice. At 2 weeks of age, no differences in collagen content were observed; within
      2 months, however, the dermis of SPARC-null mice displayed a reduced collagen
      content that persisted through adulthood until approximately 20 months, when
      collagen levels of SPARC-null skin approximated those of wild-type controls. The
      collagen fibrils present in SPARC-null skin were smaller and more uniform in
      diameter, in comparison with those of wild-type skin. At 5 months of age, the
      average fibril diameter in SPARC-null versus wild-type skin was 60.2 nm versus
      87.9 nm, respectively. Extraction of soluble dermal collagen revealed a relative
      increase in collagen VI, accompanied by a decrease in collagen I, in SPARC-null
      mice. A reduction in the relative amounts of higher-molecular weight collagen
      complexes was also observed in extracts of dermis from SPARC-null animals. Thus
      the absence of SPARC compromises the mechanical properties of the dermis, an
      effect that we attribute, at least in part, to the changes in the structure and
      composition of its collagenous extracellular matrix.

PMID- 12787120
TI  - Insulin-like growth factor-I enhances transforming growth factor-beta-induced
      extracellular matrix protein production through the P38/activating transcription
      factor-2 signaling pathway in keloid fibroblasts.
AB  - Keloids are benign dermal tumors, characterized by invasive growth of fibroblasts
      and concomitant increased biosynthesis of extracellular matrix components, with
      unclear etiology. We previously demonstrated that keloid fibroblasts overexpress
      insulin-like growth factor-I receptor. In investigating the role of insulin-like
      growth factor-I receptor overexpression, insulin-like growth factor-I and
      transforming growth factor-beta interaction was examined in relation to
      extracellular matrix protein production in cultured human and mouse fibroblasts.
      Western blotting revealed that collagen type I was expressed in keloid and normal
      fibroblasts, and its expression was increased by transforming growth factor-beta
      stimulation more significantly in keloid rather than in normal fibroblasts.
      Insulin-like growth factor-I and transforming growth factor-beta1 costimulation
      markedly increased extracellular matrix proteins (collagen type I, fibronectin,
      and plasminogen activator inhibitor-1) compared with cultures with transforming
      growth factor-beta1 alone. Insulin-like growth factor-I treatment alone had no
      stimulatory effect. Real-time reverse transcription-polymerase chain reaction
      confirmed parallel collagen type I messenger RNA level changes. Luciferase assays
      were conducted to investigate intracellular signaling pathways in this
      synergistic stimulation using a mouse fibroblast cell line. Transforming growth
      factor-beta1 (1 or 10 ng per ml) increased the specific signaling activity
      approximately 10-fold, whereas the increase with insulin-like growth factor-I
      (100 ng per ml) was less than 2-fold compared with basal activity; however, the
      combination of transforming growth factor-beta1 and insulin-like growth factor-I
      resulted in an approximately 25-fold increase. Insulin-like growth factor-I
      markedly enhanced transforming growth factor-beta-induced phosphorylation of p38
      mitogen-activated protein kinase and activating transcription factor-2.
      Luciferase assay showed that this synergistic effect was attenuated by the p38
      mitogen-activated protein kinase specific inhibitor SB203580 or
      phosphatidylinositol 3-kinase inhibitor wortmannin, but not by the mitogen
      activated protein kinase/extracellular-signal-regulated protein kinase kinase
      inhibitor PD98059. These results indicate that insulin-like growth factor-I
      enhances transforming growth factor-beta-induced keloid formation through
      transforming growth factor-beta postreceptor signal cross-talk, mainly via the
      p38 mitogen-activated protein kinase/activating transcription factor-2 pathway.

PMID- 12787121
TI  - Novel SLC39A4 mutations in acrodermatitis enteropathica.
AB  - Acrodermatitis enteropathica is an autosomal recessive disease characterized by
      skin involvement due to defective intestinal zinc absorption. Usually, the skin
      lesions include erythema, erosions, and small blisters in perioral, perianal
      regions, and hands and feet, which develop soon after weaning from the breast.
      The acrodermatitis enteropathica gene has been localized to chromosomal region
      8q24.3 and subsequently the SLC39A4 gene has been disclosed as the acrodermatitis
      enteropathica gene. SLC39A4 mutations have been demonstrated in several
      acrodermatitis enteropathica families, and in this study we have examined two
      Japanese acrodermatitis enteropathica families for SLC39A4 mutations. The
      mutation detection strategy consisted of polymerase chain reaction amplification
      of all 12 exons and flanking intronic sequences, followed by direct nucleotide
      sequencing. It revealed three novel mutations, 1017ins53, which creates a
      premature termination codon, and two mis-sense mutations, R95C and Q303H.

PMID- 12787122
TI  - A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish
      families with mal de Meleda: evidence of a founder effect.
AB  - Mal de Meleda is a rare form of palmoplantar keratoderma, and recently mutations
      in the ARS (component) B gene have been identified in families with this disease.
      We identified a recurrent nonsense mutation, R96X, in four families of Turkish
      descent. In this report, we demonstrate that these families share a common
      ancestral haplotype at the mal de Meleda locus, suggesting a founder effect.

PMID- 12787123
TI  - Genomic sequence analysis of the mouse desmoglein cluster reveals evidence for
      six distinct genes: characterization of mouse DSG4, DSG5, and DSG6.
AB  - The desmosomal cadherins, comprising the desmogleins and desmocollins, are
      calcium-dependent transmembrane adhesion molecules that are essential for the
      cell adhesive role of desmosomes. Until recently, three mouse and three human
      desmoglein isoforms had been characterized that are expressed in a tissue- and
      differentiation-specific manner. Very recently, however, we revealed genetic
      evidence for the presence of a fourth human gene, DSG4. Here we present genetic
      evidence for the mouse DSG4 homolog as well as two additional novel mouse
      desmoglein genes situated within the mouse cluster. We have named these two new
      genes DSG5 and DSG6, both of which demonstrate close homology with mouse DSG1.
      Mouse DSG4 comprises 16 exons spanning 36 kb of 18q, whereas DSG5 and DSG6
      comprise 15 exons spanning approximately 33 kb and 37 kb, respectively, of 18q.
      The mouse desmoglein 4 transcript contains an open reading frame of 3123 bp,
      encoding a precursor of 1041 amino acids. The desmoglein 5 transcript contains an
      open reading frame of 3180 bp encoding a precursor of 1060 amino acid residues,
      and the desmoglein 6 transcript contains an open reading frame of 2733 bp
      encoding a precursor of 911 amino acid residues. Using mouse tissue cDNA we have
      demonstrated that mouse desmogleins 4, 5, and 6 are all expressed in the
      epidermis but are expressed during different times of mouse development.

PMID- 12787124
TI  - Current pitfalls in the measurement of the 4977 bp mitochondrial DNA common
      deletion in human skin.

PMID- 12787125
TI  - CX-659S, a diaminouracil derivative, indirectly inhibits the function of
      Langerhans cells by blocking the MEK1/2-Erk1/2 pathway in keratinocytes.
AB  - Keratinocytes are an important component of the skin immune system, and
      keratinocyte-derived cytokines control the function of Langerhans cells. We
      previously showed that CX-659S, a novel diaminouracil derivative, had an
      inhibitory effect on hapten-induced contact hypersensitivity reaction in mice. In
      this study, we investigated the mechanism by which CX-659S elicits its inhibitory
      effect. CX-659S inhibited the expressions of CD80 and CD86, but not that of CD54,
      on Langerhans cells in epidermal cell suspensions. Exogenous granulocyte
      macrophage colony-stimulating factor restored the CX-659S-induced inhibition of
      CD80 and CD86 expressions of Langerhans cells. The production of interleukin-2
      from allogeneic T cells was also inhibited when the cells were stimulated with CX
      659S-treated epidermal cells, and this inhibition was suppressed by the addition
      of granulocyte-macrophage colony-stimulating factor during CX-659S treatment. As
      CX-659S significantly inhibited production of granulocyte-macrophage colony
      stimulating factor from keratinocytes, CX-659S was thought to indirectly affect
      Langerhans cells by inhibiting the function of keratinocytes. These effects of CX
      659S were preceded by blockade of the phosphorylation of extracellular-signal
      regulated kinase 1/2 and their direct activators, mitogen-activated protein
      kinase/extracellular-signal-regulated kinase 1/2 (MEK1/2), but not p38 mitogen
      activated protein kinase or inhibitory nuclear factor kappaBalpha, in
      keratinocytes. Furthermore, a specific MEK1/2 inhibitor, U0126, mimicked the
      effect of CX-659S. CX-659S, a keratinocyte-response modifier, would be an
      effective therapeutic compound to inhibit contact hypersensitivity reaction, its
      action mechanism being different from those of other immunosuppressive agents
      such as glucocorticosteroids or cyclosporine A.

PMID- 12787126
TI  - Double-stranded RNA-exposed human keratinocytes promote Th1 responses by inducing
      a Type-1 polarized phenotype in dendritic cells: role of keratinocyte-derived
      tumor necrosis factor alpha, type I interferons, and interleukin-18.
AB  - Dendritic cells play a key role in establishing the class of immune response
      against invading pathogens. Upon engagement with double-stranded RNA, a major
      bioactive constituent of many virus types, immature dendritic cells develop into
      type 1 immunostimulatory dendritic cells that promote Th1 responses. Immature
      dendritic cells reside in the epithelia and are in close contact with
      keratinocytes. We studied to what extent dendritic cells can also adopt a type 1
      immunostimulatory dendritic cell phenotype indirectly, as a result of the
      interaction with keratinocytes responding to double-stranded RNA. In contrast to
      supernatants from keratinocytes activated by the combination of tumor necrosis
      factor alpha and interleukin-1beta, supernatants from keratinocytes activated by
      synthetic double-stranded RNA, polyriboinosinic polyribocytidylic acid, comprised
      tumor necrosis factor alpha and type I interferons, which induced maturation of
      human monocyte-derived immature dendritic cells. In addition, dendritic cells
      matured in the presence of these supernatants strongly biased the development of
      Th1 cells from naive Th cells. This bias was dependent on keratinocyte-derived
      interferon-alpha/beta and interleukin-18, as neutralization of both interferon
      alpha/beta and interleukin-18 in the keratinocyte culture supernatant reduced the
      development of interferon-gamma-producing Th cells. These findings suggest that
      keratinocytes can contribute to the development of selective Th1/Th2 responses
      through the induction of maturation and functional polarization of dendritic
      cells, indicating a novel role for keratinocytes as initiators and regulators of
      cutaneous T-cell-mediated inflammation. In addition, these results support the
      concept that, in addition to direct interaction with pathogens, dendritic cells
      may also be activated and primed by pathogen indirectly, via the effect of
      resident tissue cells responding to pathogen.

PMID- 12787127
TI  - Neonatal development of the stratum corneum pH gradient: localization and
      mechanisms leading to emergence of optimal barrier function.
AB  - Although basal permeability barrier function is established at birth, the higher
      risk for infections, dermatitis, and percutaneous absorption of toxic agents may
      indicate incomplete permeability barrier maturation in the early neonatal period.
      Since stratum corneum (SC) acidification in adults is required for normal
      permeability barrier homeostasis, and lipid processing occurs via acidic pH
      dependent enzymes, we hypothesized that, in parallel with the less acidic surface
      pH, newborn SC would exhibit signs of incomplete barrier formation. Fluorescence
      lifetime imaging reveals that neonatal rat SC acidification first becomes evident
      by postnatal day 3, in extracellular "microdomains" at the SC- stratum granulosum
      (SG) interface, where pH-sensitive lipid processing is known to occur. This
      localized acidification correlated temporally with efficient processing of
      secreted lamellar body contents to mature extracellular lamellar bilayers. Since
      expression of the key acidifying mechanism NHE1 is maximal just prior to birth,
      and gradually declines over the first postnatal week, suboptimal SC acidification
      at birth cannot be attributed to insufficient NHE1 expression, but could instead
      reflect reduced NHE1 activity. Expression of the key lipid processing enzyme,
      beta-glucocerebrosidase (beta-GlcCer'ase), develops similar to NHE1, excluding a
      lack of beta-GlcCer'ase protein as rate limiting for efficient lipid processing.
      These results define a postnatal development consisting of initial acidification
      in the lower SC followed by outward progression, which is accompanied by
      formation of mature extracellular lamellar membranes. Thus, full barrier
      competence appears to require the extension of acidification in microdomains from
      the SC/SG interface outward toward the skin surface in the immediate postnatal
      period.

PMID- 12787128
TI  - Purinergic receptors are part of a functional signaling system for proliferation
      and differentiation of human epidermal keratinocytes.
AB  - We investigated the expression of P2X5, P2X7, P2Y1 and P2Y2 receptor subtypes in
      normal human epidermis and in relation to markers of proliferation (PCNA and Ki
      67), keratinocyte differentiation (cytokeratin K10 and involucrin) and markers of
      apoptosis (TUNEL and anticaspase-3). Using immunohistochemistry, we showed that
      each of the four receptors was expressed in a spatially distinct zone of the
      epidermis, suggesting different functional roles for these receptors. Functional
      studies were performed on primary cultures of human keratinocytes and on
      explanted rat skin, where different P2 receptor subtype agonists and antagonists
      were applied to cultured keratinocytes or injected subcutaneously into the skin,
      respectively. An increase in cell number was caused by low doses of the
      nonspecific P2 receptor agonist ATP, the P2Y2 receptor agonist UTP (p<0.001), and
      the P2Y1 receptor agonist 2MeSADP (p<0.05). There was a significant decrease in
      cell number as a result of treatment with the P2X5 receptor agonist ATPgammaS
      (p<0.001) and the P2X7 receptor agonist BzATP (p<0.001). Suramin caused a
      significant block in the effect of 100 microm ATP (p<0.01) and 1000 microm ATP
      (p<0.001) on cell number. These results imply that different purinergic receptors
      have different functional roles in the human epidermis with P2Y1 and P2Y2
      receptors controlling proliferation, while P2X5 and P2X7 receptors control early
      differentiation, terminal differentiation and death of keratinocytes,
      respectively.

PMID- 12787129
TI  - The importance of cationic amino acid transporter expression in human skin.
AB  - Inducible nitric oxide synthase and arginase activities are acknowledged as
      important players in human skin epidermal function. For proper enzyme function
      the substrate availability of L-arginine for both enzymes and thus its transport
      across the cell membrane via the y+-system (also named cationic amino acid
      transporters) is critical. Here, we examine the expression of cationic amino acid
      transporters and their functional role in modulating inducible nitric oxide
      synthase and arginase activities in human skin and primary keratinocytes,
      fibroblasts and endothelial cells as well as their impact on keratinocyte
      proliferation. Skin biopsies were found to express constitutively both cationic
      amino acid transporter-1 and cationic amino acid transporter-2 mRNA, an
      expression pattern known to occur in hepatocytes and muscle cells only. To
      determine the cellular components expressing cationic amino acid transporter, we
      analyzed the expression patterns in the different human skin cell types in vitro,
      i.e., in fibroblasts, dermal endothelial cells, and keratinocytes as well as in
      the HaCaT cell line. An ubiquitous cationic amino acid transporter-1 mRNA
      expression was found in all cells, whereas constitutive cationic amino acid
      transporter-2 mRNA expression occurs in resident keratinocytes and dermal
      endothelial cells only. De novo induction of cationic amino acid transporter-2
      and inducible nitric oxide synthase by proinflammatory cytokines was seen in
      fibroblasts and HaCaT. Competitive inhibition of the cationic amino acid
      transporter-mediated L-arginine transport by culturing primary human
      keratinocytes in the presence of increased L-lysine concentration led to
      decreased inducible nitric oxide synthase and arginase activities with a
      concomitant significant decrease in keratinocyte proliferation. In summary, our
      results demonstrate that human keratinocytes constitutively express cationic
      amino acid transporters 1 and 2 and that cationic amino acid transporter mediated
      L-arginine influx, is essential for both inducible nitric oxide synthase and
      arginase enzyme activities, which in turn modulate proliferation and
      differentiation of human epidermal skin cells.

PMID- 12787130
TI  - NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis.
AB  - Glutamate receptors play an important role in the excitatory synaptic action of
      the central nervous system. In this study, effects of glutamate receptor agonists
      and antagonists on skin barrier homeostasis were studied using hairless mouse.
      Topical application of L-glutamic acid, L-aspartic acid (non-specific glutamate
      receptor agonists) and N-methyl-D-aspartate (NMDA, NMDA type receptor agonist)
      delayed the barrier recovery rate after barrier disruption with tape stripping.
      On the other hand, topical application of D-glutamic acid (non-specific
      antagonist of glutamate receptor), MK 801 and D-AP5, (NMDA-type receptor
      antagonists) accelerated the barrier repair. The non-NMDA type receptor agonist,
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), did not affect the
      barrier recovery. Topical application of MK-801 also promoted the healing of
      epidermal hyperplasia induced by acetone treatment under low environmental
      humidity. Immediately after barrier disruption on skin organ culture, secretion
      of glutamic acid from skin was significantly increased. Immunohistochemistry,
      reverse transcription polymearse chain reaction (RT-PCR) and in situ
      hybridization showed an expression of NMDA-type receptor-like protein on hairless
      mouse epidermis. NMDA increased intercellular calcium in cultured human
      keratinocytes and the increase was blocked by MK 801. These results suggest that
      glutamate plays an important role as a signal of cutaneous barrier homeostasis
      and epidermal hyperplasia induced by barrier disruption.

PMID- 12787131
TI  - Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated
      by transforming growth factor beta autoinduction: a negative feedback mechanism
      for keratinocyte growth.
AB  - The epidermal growth factor receptor and its ligands initiate a major signaling
      pathway that regulates keratinocyte growth in an autocrine manner. It is well
      known that high doses of epidermal growth factor receptor ligands inhibit
      keratinocyte growth. Recently, signal transducers and activators of transcription
      1-dependent p21Waf1/Cip1 induction were reported to be involved in high-dose
      epidermal growth factor-dependent cell growth arrest in the A431 squamous cell
      carcinoma cell line; however, transfection of dominant-negative signal
      transducers and activators of transcription 1 adenovirus vector did not block
      epidermal growth factor-induced growth inhibition in normal human keratinocytes.
      As transforming growth factor beta is a potent inhibitor of keratinocyte
      proliferation, we hypothesized that transforming growth factor beta contributes
      to epidermal growth factor-mediated keratinocyte growth inhibition. Epidermal
      growth factor concentrations of 10 ng per ml enhanced transforming growth factor
      beta1 mRNA expression from 3 to 6 h poststimulation. Enzyme-linked immunosorbent
      assay analysis detected 150 pg per ml of transforming growth factor beta1 in the
      culture medium of keratinocytes incubated with 10 and 100 ng per ml epidermal
      growth factor, whereas 0.1 and 1.0 ng per ml epidermal growth factor slightly
      enhance transforming growth factor beta1 production. Epidermal growth factor (100
      ng per ml) upregulated luciferase activity of p3TP-lux, which contains three
      tandem transforming growth factor beta-Smad signaling responsive elements, 6-fold
      compared with unstimulated cells. The epidermal growth factor-dependent induction
      of p3TP-lux luciferase activity was disrupted by transfection of the dominant
      negative form of transforming growth factor beta type I receptor adenovirus
      vector (AxdnALK5), which suggests that epidermal growth factor-induced
      transforming growth factor beta acts in an autocrine manner in keratinocytes.
      Moreover, transfection of AxdnALK5 completely blocked the growth inhibition
      induced by 100 ng per ml of epidermal growth factor in normal keratinocytes.
      These data demonstrate that an autocrine transforming growth factor beta1-ALK5
      pathway is a negative feedback mechanism for epidermal growth factor-induced
      normal human keratinocyte growth.

PMID- 12787132
TI  - EGF upregulates, whereas TGF-beta downregulates, the hyaluronan synthases Has2
      and Has3 in organotypic keratinocyte cultures: correlations with epidermal
      proliferation and differentiation.
AB  - Hyaluronan, a major extracellular matrix molecule in the vital cell layers of
      skin epidermis, has been suggested to support proliferation and migration of
      keratinocytes, during challenges like wounding and inflammation. An organotypic
      keratinocyte culture originated from continuous rat epidermal keratinocyte cell
      line was subjected to the proliferative and antiproliferative growth factors
      epidermal growth factor and transforming growth factor beta, respectively, to
      study their influence on hyaluronan synthesis and epidermal morphology. Epidermal
      growth factor induced a 4-fold increase of epidermal hyaluronan concentration.
      This was associated with upregulation of the hyaluronan synthases Has2 and Has3,
      and the hyaluronan receptor CD44. 5-Bromo-2'-deoxyuridine labeling, basal cell
      height, and the thickness of vital epidermis were increased, reflecting the
      hyperplastic effects of epidermal growth factor. The expression of keratin 10 and
      the maturation of filaggrin were inhibited, and epidermal permeability barrier
      became less efficient, indicating compromised terminal differentiation by
      epidermal growth factor. In contrast, transforming growth factor beta reduced the
      content of hyaluronan and the mRNA of Has2 and Has3. At the same time,
      transforming growth factor beta suppressed keratinocyte proliferation and
      epidermal thickness, but retained intact differentiation. The results suggest
      that epidermal hyaluronan synthesis, controlled by epidermal growth factor and
      transforming growth factor beta through changes in the expression of Has2 and
      Has3, correlates with epidermal proliferation, thickness, and differentiation.

PMID- 12787133
TI  - HAX-1, identified by differential display reverse transcription polymerase chain
      reaction, is overexpressed in lesional psoriasis.
AB  - Psoriasis is a chronic inflammatory disease characterized by epidermal
      hyperplasia and an inflammatory infiltrate. The normal differentiation from basal
      to granular keratinocytes with subsequent apoptosis and cornification is
      disturbed in the akanthotic epidermis. This could be due to both an excess of
      mitogenic stimuli with hyperproliferation and/or resistance to apoptosis. By mRNA
      differential display we found HAX-1 to be overexpressed in lesional psoriatic
      skin. The overexpression of HAX-1 was verified at the mRNA level by Northern blot
      and in situ hybridization, as well as at the protein level by Western blot and
      immunohistochemistry. Detection of HAX-1 in mRNA from different tissues showed
      strong expression in the brain, pancreas, skeletal muscle, and heart. In contrast
      to primary keratinocytes and melanocytes we found HAX-1 highly expressed in human
      immortalized keratinocytes (HaCaT) and different melanoma cell lines. In HaCaT
      cells as a model for psoriatic keratinocytes we found an increased ultraviolet
      induced apoptosis after expression of HAX-1 antisense mRNA. In psoriasis, the
      epidermal differentiation could be disturbed due to the increased expression of
      HAX-1 and hence a prolonged resistance to terminal differentiation. Antiapoptotic
      mechanisms are an emerging concept for the understanding of the pathogenesis of
      this disease possibly leading to clinical applications.

PMID- 12787134
TI  - Desmoglein isotype expression in the hair follicle and its cysts correlates with
      type of keratinization and degree of differentiation.
AB  - Within stratified squamous epithelia, such as the epidermis, desmogleins are
      generally expressed in a differentiation-specific manner. Similar to the
      epidermis, the hair follicle is compartmentalized into a hierarchy of cell types
      based on their level of differentiation. Relatively undifferentiated stem cells
      in the bulge can generate epidermis, sebaceous gland, and hair bulb matrix cells.
      The latter give rise to at least six different cell types that keratinize as they
      move up the hair shaft and inner root sheath. Here, we examined expression
      patterns of the desmoglein isotypes, desmogleins 1, 2, and 3 in the cutaneous
      epithelium, and discovered that desmoglein 1 and 2 expression correlated with the
      state of differentiation of defined populations within the hair follicle.
      Desmoglein 2 was highly expressed by the least differentiated cells of the
      cutaneous epithelium, including the hair follicle bulge of the fetus and adult,
      bulb matrix cells, and basal layer of the outer root sheath. In contrast,
      desmoglein 1 defined more differentiated cell populations, and was expressed in
      epidermal suprabasal cells, the inner root sheath, and the innermost layers of
      the outer root sheath. We found that the expression pattern of desmoglein 3
      correlated with different types of keratinization. In areas of trichilemmal
      keratinization in the follicle, and in cysts arising from these areas, desmoglein
      3 was expressed throughout all layers of the outer root sheath and cyst wall. In
      areas of epidermal-like keratinization, such as in the infundibulum and in
      epidermal inclusion cysts, desmoglein 3 expression was limited mainly to the
      basal layer. We conclude that desmoglein expression patterns define compartments
      of cells in similar states of differentiation within the cutaneous epithelium,
      and reveal a hierarchy of differentiation among these compartments.

PMID- 12787135
TI  - 17Beta-estradiol inhibits MCP-1 production in human keratinocytes.
AB  - A chemokine, monocyte chemoattractant protein 1 (MCP-1), attracts macrophages.
      The production of MCP-1 is enhanced in keratinocytes of psoriatic lesions, which
      may contribute to macrophage infiltration into the lesions. It is known that
      estrogen regulates the course of psoriasis. We examined in vitro effects of
      17beta-estradiol (E2) on MCP-1 production by human keratinocytes. E2 inhibited
      constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced MCP-1 secretion,
      mRNA expression, and promoter activity in keratinocytes, and these effects of E2
      were counteracted by estrogen receptor antagonist ICI 182 780. GC-rich Sp1
      element and activator protein 1 (AP-1) element on MCP-1 promoter were required
      for constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced transcription,
      respectively, and involved in transrepression by E2. E2 inhibited constitutive
      Sp1 and 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 transcriptional
      activities whereas it did not inhibit DNA binding of Sp1 or AP-1 c-Fos/c-Jun. E2
      inhibited Sp1 and AP-1 transcriptional activities and MCP-1 promoter activity in
      estrogen receptor beta (ERbeta) transfected SKBR3 cells. Deletion of the A/B
      region or mutation of activation function 2 in ERbeta abrogated E2-dependent
      transcriptional inhibition by ERbeta whereas mutation of DNA-binding domain
      retained the inhibitory effects. Transfection of ERbeta enhanced the inhibitory
      effects of E2 on Sp1 and AP-1 transcriptional activities and MCP-1 promoter
      activities in nontransfected keratinocytes. Coimmunoprecipitation studies showed
      an E2-dependent association of ERbeta with Sp1 or AP-1 in ERbeta-transfected
      keratinocytes. These results suggest that E2-bound ERbeta may inhibit MCP-1 gene
      expression by inhibiting Sp1 and AP-1 transcriptional activities in
      keratinocytes. A/B region and intact activation function 2 of ERbeta may be
      responsible for the effects of E2.

PMID- 12787136
TI  - The potential impact on melanoma mortality of reducing rates of suboptimal
      excision margins.
AB  - We estimated the potential benefit of reducing rates of inadequate excision
      margins in the treatment of localized invasive melanoma. A computer-simulated
      Markov decision analytic model was created to follow until death a hypothetical
      cohort of 55 y old Caucasians, newly diagnosed in a community setting with
      localized invasive melanoma. We considered two scenarios: usual care, and a
      hypothetical intervention. Markov states included well without local recurrence,
      local recurrence, cured, and dead. Published population-based data were used for
      rates of optimal excision margins, local recurrence, and mortality. Two outcome
      measures were employed: melanoma-related mortality and life expectancy. Major
      assumptions included: local recurrence occurs within 10 y of diagnosis, and
      patients revert to general population mortality rates 10 y following melanoma
      excision or subsequent local recurrence. For usual care, the model estimated
      8.17% melanoma-related mortality. Modeling intervention with 100% optimal
      excision margins reduced this rate to 6.15%, a 25% relative reduction in
      mortality. This increased average life expectancy by 0.437 y, which equates to
      approximately 11 additional years in the 4% who would not experience a local
      recurrence due to improved excision margins. Increasing the percentage of optimal
      excision margins to 80% would still yield substantial improvement, with 6.83%
      melanoma-related mortality, saving 0.29 life-years compared with baseline.
      Results were insensitive to moderate changes in the parameter values. Suboptimal
      excision margins may account for approximately one-fourth of all melanoma-related
      mortality for localized invasive melanoma. If intervention can achieve even
      modest adherence to optimal excision margins, it might substantially reduce
      mortality.

PMID- 12787137
TI  - Regulation of human epidermal melanocyte biology by beta-endorphin.
AB  - beta-Endorphin is an opioid peptide cleaved from the precursor pro-hormone pro
      opiomelanocortin, from which other peptides such as adrenocorticotropic hormone,
      beta-lipotropic hormone, and alpha-melanocyte-stimulating hormone are also
      derived. alpha-Melanocyte-stimulating hormone and adrenocorticotropic hormone are
      well documented to regulate human skin pigmentation via action at the
      melanocortin-1 receptor. Whereas plasma beta-endorphin is reported to increase
      after exposure to ultraviolet radiation, to date a functional role for beta
      endorphin in the regulation of human epidermal melanocyte biology has not been
      demonstrated. This study was designed to examine the involvement of the beta
      endorphin/mu-opiate receptor system in human epidermal melanocytes. To address
      this question we employed reverse transcription-polymerase chain reaction, and
      immunohistochemistry/cytochemistry and immunoelectron microscopy using beta
      endorphin and mu-opiate receptor specific antibodies. A functional role for beta
      endorphin was assessed in epidermal melanocyte cultures by direct stimulation
      with the peptide. This study demonstrated the expression of mu-opiate receptor
      mRNA in cultured epidermal melanocytes, as well as mRNA for pro-opiomelanocortin.
      In addition, we have shown that beta-endorphin and mu-opiate receptor are
      expressed at the protein level in situ in glycoprotein100-positive melanocytes.
      The expression of both beta-endorphin and mu-opiate receptor correlated
      positively with their differentiation status in vitro. Furthermore,
      immunoelectron microscopy studies revealed an association of beta-endorphin with
      melanosomes. Functional studies showed that beta-endorphin has potent
      melanogenic, mitogenic, and dendritogenic effects in cultured epidermal
      melanocytes deprived of any exogenous supply of pro-opiomelanocortin peptides.
      Thus, we report that human epidermal melanocytes express a fully functioning beta
      endorphin/mu-opiate receptor system. In the absence of any data showing cross
      talk between the mu-opiate receptor and the melanocortin-1 receptor, we conclude
      that the beta-endorphin/mu-opiate receptor system participates in the regulation
      of skin pigmentation.

PMID- 12787138
TI  - Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse
      xenotransplantation model.
AB  - It is well established that high expression of the antiapoptotic Bcl-2 family
      proteins Bcl-2 and Bcl-xL can significantly contribute to chemoresistance in a
      number of human malignancies. Much less is known about the role the more recently
      described Bcl-2 family member Mcl-1 might play in tumor biology and resistance to
      chemotherapy. Using an antisense strategy, we here address this issue in
      melanoma, a paradigm of a treatment-resistant malignancy. After in vitro proof of
      principle supporting an antisense mechanism of action with specific reduction of
      Mcl-1 protein as a consequence of nuclear uptake of the Mcl-1 antisense
      oligonucleotides employed, antisense and universal control oligonucleotides were
      administered systemically in combination with dacarbazine in a human melanoma
      SCID mouse xenotransplantation model. Dacarbazine, available now for more than
      three decades, still remains the most active single agent for treatment of
      advanced melanoma. Mcl-1 antisense oligonucleotides specifically reduced target
      protein expression as well as the apoptotic threshold of melanoma
      xenotransplants. Combined Mcl-1 antisense oligonucleotide plus dacarbazine
      treatment resulted in enhanced tumor cell apoptosis and led to a significantly
      reduced mean tumor weight (mean 0.16 g, 95% confidence interval 0.08-0.26)
      compared to the tumor weight in universal control oligonucleotide plus
      dacarbazine treated animals (mean 0.35 g, 95% confidence interval 0.2-0.44) or
      saline plus dacarbazine treated animals (mean 0.39 g, 95% confidence interval
      0.25-0.53). We thus show that Mcl-1 is an important factor contributing to the
      chemoresistance of human melanoma in vivo. Antisense therapy against the Mcl-1
      gene product, possibly in combination with antisense strategies targeting other
      antiapoptotic Bcl-2 family members, appears to be a rational and promising
      approach to help overcome treatment resistance of malignant melanoma.

PMID- 12787139
TI  - The influence of painful sunburns and lifetime sun exposure on the risk of
      actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin
      cancer.
AB  - Painful sunburns are implicated in the pathogenesis of squamous cell carcinoma,
      basal cell carcinoma, and malignant melanoma. Chronic exposure to ultraviolet
      radiation is known as the most important risk factor for the development of
      actinic keratoses and squamous cell carcinoma. The purpose of the study was to
      assess the effect of painful sunburns and lifetime sun exposure on the
      development of actinic keratoses and seborrheic warts in relation to the
      development of squamous cell carcinoma and basal cell carcinoma, and on the
      development of melanocytic nevi and atypical nevi in relation to the development
      of malignant melanoma. We made use of a cohort of 966 individuals who
      participated in a case-control study to investigate environmental and genetic
      risk factors for skin cancer. Exposure measurements for sunlight were collected
      and actinic keratoses, seborrheic warts, melanocytic nevi, and atypical nevi were
      counted. Relative risks were estimated using exposure odds ratios from cross
      tabulation. Multivariate logistic regression was used to adjust for potential
      confounders. The recall of painful sunburns before the age of 20 y was associated
      with an increased risk of squamous cell carcinoma, nodular basal cell carcinoma,
      and multifocal superficial basal cell carcinoma as well as actinic keratoses.
      Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type
      were 1.5 (0.97; 2.3); 1.6 (1.1; 2.2); 2.6 (1.7; 3.8); and 1.9 (1.4; 2.6) for the
      three types of nonmelanoma skin cancer and actinic keratoses, respectively.
      Painful sunburns before the age of 20 y were also associated with an increased
      risk of malignant melanoma and the development of its precursors, melanocytic
      nevi and atypical nevi. Odds ratios with 95% confidence intervals adjusted for
      age, sex, and skin type were 1.4 (0.86; 2.1); 1.5 (1.1; 2.0); and 1.4 (0.88; 2.3)
      for malignant melanoma and the two types of precursors, respectively. Lifetime
      sun exposure was predominantly associated with an increased risk of squamous cell
      carcinoma (p-value for trend=0.03) and actinic keratoses (p-value for trend
      <0.0001) and to a lesser degree with the two types of basal cell carcinoma. By
      contrast, lifetime sun exposure appeared to be associated with a lower risk of
      malignant melanoma, despite the fact that lifetime sun exposure did not diminish
      the number of melanocytic nevi or atypical nevi. Neither painful sunburns nor
      lifetime sun exposure were associated with an increased risk of seborrheic warts.

PMID- 12787140
TI  - Fas ligand downregulation with antisense oligonucleotides in cells and in
      cultured tissues of normal skin epidermis and basal cell carcinoma.
AB  - Fas ligand (FasL), a member of the tumor necrosis factor family, induces
      apoptosis upon interaction with Fas-receptor-expressing cells. FasL normally
      plays an important immune regulatory role, but it can also cause severe skin
      diseases if overexpressed and it may serve some tumors for immune evasion. Thus,
      in situ inhibition of FasL expression with antisense oligonucleotides in patients
      may be a novel approach to overcome its pathogenic role. We designed and
      evaluated 15 phosphorothioate antisense oligonucleotides directed against
      different regions of the human FasL mRNA. They exhibited different inhibitory
      activities on FasL expression in HEK293 cells. The most potent antisense
      oligonucleotide, ASO8, specifically downregulated 90% FasL expression at the
      protein level and 80% at the mRNA level. FasL downregulation reduced the effector
      function of HEK293 cells toward Fas receptor positive target cells. Further
      studies demonstrated that ASO8 efficiently inhibited FasL synthesis in split skin
      and basal cell carcinoma tissue. Our results show that the modulation of FasL
      expression by antisense oligonucleotides is possible in cells as well as tissue
      and indicate that antisense oligonucleotides may provide a promising strategy for
      the therapy of FasL-mediated disorders.

PMID- 12787142
TI  - Glu-Leu-Arg-negative CXC chemokine interferon gamma inducible protein-9 as a
      mediator of epidermal-dermal communication during wound repair.
AB  - Normal wound healing is a complex, highly regulated dynamic process that requires
      co-ordinate responses of both epidermal and dermal compartments. To accomplish
      the healing process several growth factors, chemokines, and matrix elements
      signal both cell proliferation and migration during the inflammatory and
      reparative phases and limit these responses during the remodeling phase. We have
      found that the Glu-Leu-Arg-negative CXC chemokines interferon gamma inducible
      protein 10, monokine induced by interferon gamma, and platelet factor 4, limit
      fibroblast responsiveness to growth factors, but the functioning of these factors
      in wound healing remains uncertain. We hypothesized that the keratinocyte-derived
      member of this Glu-Leu-Arg-negative CXC family, interferon gamma inducible
      protein 9 (IP-9) CXCL11 (also known as I-TAC, beta-R1, and H-174) signals to the
      dermal compartment to synchronize the re-epithelialization process. Interferon
      gamma inducible protein 9 was produced after mechanical wounding of a
      keratinocyte monolayer, suggesting for the first time that this could be a wound
      response factor. Interferon gamma inducible protein 9 limited epidermal growth
      factor (EGF)-induced fibroblast motility (57+/-7%) by the same protein kinase A
      (KA)-mediated inhibition of calpain activation and cell de-adhesion as described
      for interferon gamma inducible protein 10. Surprisingly, interferon gamma
      inducible protein 9 enhanced growth factor-induced motility in undifferentiated
      keratinocytes (137+/-19%) as determined in a two-dimensional in vitro wound
      healing assay, and interferon gamma inducible protein 9 alone promoted motility
      in undifferentiated keratinocytes (49+/-10% of epidermal growth factor-induced
      motility). A stimulated keratinocyte/target cell coculture system revealed that
      interferon gamma inducible protein 9 acts as a soluble keratinocyte-derived
      paracrine factor for both fibroblasts and keratinocytes. Further, we found that
      in both fibroblasts and undifferentiated keratinocytes, interferon gamma
      inducible protein 9 exerted its action through modulation of a cytosolic
      protease, calpain. Interestingly, interferon gamma inducible protein 9 increased
      calpain activity in undifferentiated keratinocytes, whereas the same chemokine
      inhibited the calpain activity in fibroblasts. This provides for a model whereby
      redifferentiated basal keratinocytes could limit fibroblast repopulation of the
      dermis underlying healed wounds while simultaneously promoting re
      epithelialization of the remaining provisional wound.

PMID- 12787141
TI  - Functional overlap and cooperativity among alphav and beta1 integrin subfamilies
      during skin angiogenesis.
AB  - Angiogenesis requires endothelial cell survival and proliferation, which depend
      upon cytokine stimulation together with integrin-mediated cell adhesion to
      extracellular matrix; however, the question of which specific integrins are the
      best targets for suppressing neovascularization is controversial and unresolved.
      Therefore, we designed experiments to compare contributions of individual
      integrins from both the alphav and beta1 integrin subfamilies. With immobilized
      antibodies, we determined that adhesion through integrins alpha1beta1,
      alpha2beta1, alphavbeta3, and alphavbeta5 each individually supported dermal
      microvascular endothelial cell survival. Also, substratum coated with collagen I
      (which binds alpha1beta1 and alpha2beta1) and vitronectin (which binds
      alphavbeta3 and alphavbeta5) each supported survival. Importantly, substratum
      coated with combinations of collagen I and vitronectin were most effective at
      promoting survival, and survival on three-dimensional collagen I gels was
      strongly enhanced by vitronectin. Vascular endothelial growth factor activation
      of the p44/p42 mitogen-activated protein kinase pathway, which is required for
      angiogenesis, was supported by adhesion through either alpha1beta1, alpha2beta1,
      alphavbeta3, or alphavbeta5, and pharmacologic inhibition of this pathway blocked
      proliferation and suppressed survival. Therefore, these studies establish that
      the alpha1beta1, alpha2beta1, alphavbeta3, and alphavbeta5 integrins each support
      dermal microvascular endothelial cell viability, and that each collaborate with
      vascular endothelial growth factor to support robust activation of the mitogen
      activated protein kinase pathway which mediates both proliferation and survival.
      Moreover, survival is supported most significantly by extracellular matrices,
      which engage all of these integrins in combination. Consistent with important
      complementary and overlapping functions, combined antagonism of these integrins
      provided superior inhibition of angiogenesis in skin, indicating that
      multiplicity of integrin involvement should be considered in designing strategies
      for controlling neovascularization.

PMID- 12787143
TI  - Differential effect of wounding on actin and its associated proteins, paxillin
      and gelsolin, in fetal skin explants.
AB  - Skin from the embryonic day 17 rat retains the ability to epithelialize an
      excisional wound when isolated in serum-supplemented suspension culture. This
      ability is lost by embryonic day 19. We have investigated this effect of
      gestational age on fetal epithelial wound closure by correlating the involvement
      of filamentous actin (F-actin) and its associated proteins, paxillin and
      gelsolin, in the wound margins of embryonic day 17 and 19 rat skins, with the
      ability to close a full thickness excisional wound. Using fluorescent-phalloidin
      histochemistry and scanning confocal microscopy, actin polymerization was
      observed some five to six cells back from the margin of wounds in the embryonic
      day 17 skin as early as 3 h postwounding. As the wounds closed over the following
      48-72 h, the actin further condensed around the epithelial margin before
      dispersing after wound closure. In contrast, no organization of actin was seen in
      the epithelial margin of wounds in skin from the embryonic day 19 embryos.
      Instead, actin filaments were observed surrounding the dermal wound margins.
      Chemical or mechanical disruption of the actin in wounded embryonic day 17 skins
      prevented epithelial closure, although wound repair was independent of cell
      division. In particular, incising the wound margin 24 h after wounding resulted
      in the "springing-open" of the embryonic day 17 wound but not the embryonic day
      19 wound, reflecting the development of tension in the embryonic day 17 wound
      margin. Expression of paxillin mRNA was upregulated following wounding at
      embryonic day 17 but not at embryonic day 19. Paxillin was also observed to
      colocalize with actin in embryonic day 17 wounds, but not embryonic day 19
      wounds, indicating a potential role for paxillin in epithelial repair of the
      fetal wound. In contrast, gelsolin mRNA was upregulated in embryonic day 19 fetal
      skin but not at embryonic day 17 and gelsolin protein was observed surrounding
      actin filaments at embryonic day 19 but not embryonic day 17. These results
      demonstrate a change in the mechanism of wound epithelialization at the same
      gestational age that fetal wounds change from scar-free to scar-forming wound
      repair.

PMID- 12787144
TI  - The effect of thrombocytopenia on dermal wound healing.
AB  - The immediate appearance of platelets in wounds and the ability of platelets to
      release growth factors suggest that platelets are an important trigger of the
      tissue repair process. To examine the effect of systemic thrombocytopenia on both
      the inflammatory and proliferative aspects of wound healing, adult mice were
      rendered thrombocytopenic by intraperitoneal administration of a rabbit antimouse
      platelet serum. Full-thickness excisional dermal wounds were prepared and
      analyzed for inflammatory cell content, growth factor production,
      reepithelialization, collagen synthesis, and angiogenesis at multiple time points
      after injury. Compared to control mice, thrombocytopenic mice exhibited
      significantly altered wound inflammation. Wounds of thrombocytopenic mice
      contained significantly more macrophages and T cells, yet exhibited neutrophil
      content similar to wounds from control mice. Surprisingly, thrombocytopenic mice
      exhibited no delay in the reparative aspects of wound healing. The rate of wound
      reepithelialization, collagen synthesis, and angiogenesis was nearly identical
      for thrombocytopenic and control mice. Analysis of vascular endothelial growth
      factor, fibroblast growth factor 2, transforming growth factor beta1,
      keratinocyte growth factor, and epidermal growth factor revealed no difference in
      the levels of these growth factors in the wounds of control and thrombocytopenic
      mice. Taken together, the results suggest that the presence of platelets may
      influence wound inflammation, but that platelets do not significantly affect the
      proliferative aspects of repair, including wound closure, angiogenesis, and
      collagen synthesis.

PMID- 12787148
TI  - Epithelial-mesenchymal networks in wounds: a hierarchical view.

PMID- 12787151
TI  - Beta-endorphin/mu-opiate receptor system in the skin.

PMID- 12787152
TI  - Sebaceous gland in human skin--the fantastic future of a skin appendage.

PMID- 12787154
TI  - Pre-school children with and without developmental delay: behaviour problems and
      parenting stress over time.
AB  - BACKGROUND: Children with intellectual disability are at heightened risk for
      behaviour problems and diagnosed mental disorder. METHODS: The present authors
      studied the early manifestation and continuity of problem behaviours in 205 pre
      school children with and without developmental delays. RESULTS: Behaviour
      problems were quite stable over the year from age 36-48 months. Children with
      developmental delays were rated higher on behaviour problems than their non
      delayed peers, and were three times as likely to score in the clinical range.
      Mothers and fathers showed high agreement in their rating of child problems,
      especially in the delayed group. Parenting stress was also higher in the delayed
      group, but was related to the extent of behaviour problems rather than to the
      child's developmental delay. CONCLUSIONS: Over time, a transactional model fit
      the relationship between parenting stress and behaviour problems: high parenting
      stress contributed to a worsening in child behaviour problems over time, and high
      child behaviour problems contributed to a worsening in parenting stress. Findings
      for mothers and fathers were quite similar.

PMID- 12787155
TI  - Child behaviour problems and partner mental health as correlates of stress in
      mothers and fathers of children with autism.
AB  - BACKGROUND: Previous research has suggested that the mothers and fathers of
      children with disabilities experience stress differently. Although there has been
      a great deal of research exploring how children affect parents, there have been
      many fewer studies of the interrelationships between mothers' and fathers'
      psychological well-being. METHODS: Eighteen married couples who were the parents
      of children with autism reported on their stress and their general mental health
      (i.e. anxiety and depression). Teachers rated the behaviour problems of the
      children with autism. RESULTS: Mothers and fathers did not differ in their levels
      of stress and depression, but mothers reported more anxiety than fathers. Partial
      correlation analyses revealed that child behaviour problems and fathers' mental
      health were associated with mothers' stress. However, neither child behaviour
      problems or mothers' mental health was associated with fathers' stress.
      CONCLUSIONS: Although requiring replication, the results suggest that stress in
      mothers of children with disabilities may be affected by the psychological health
      of other family members, whereas fathers' stress is affected more by other
      factors. Methodological and conceptual issues, and the practical implications of
      these results are discussed.

PMID- 12787156
TI  - Evaluation of an intervention system for parents of children with intellectual
      disability and challenging behaviour.
AB  - BACKGROUND: Signposts is a flexible intervention system for families of children
      who have intellectual disability and challenging behaviour. The Signposts
      materials include eight information booklets, a workbook and videotape for
      parents, and a series of instructional manuals for therapists. The system was
      designed so that it can be delivered in several different ways, i.e. group
      support, telephone support and self-directed modes. METHODS: The present study
      was an evaluation of these three modes of delivery and involved 115 families.
      RESULTS: Following the use of the Signposts materials in parent training
      programmes, the subjects reported that they were less stressed, felt more
      efficacious about managing their children's behaviour, were less hassled about
      meeting their own needs and that their children's behaviour had improved.
      Additionally, families generally reported high levels of satisfaction with the
      content and delivery of the materials. CONCLUSIONS: Finally, there were minimal
      differences among the three modes of delivery on the measures used, although
      families who used the self-directed mode were less likely to complete the
      materials. Implications of these results for service delivery are discussed.

PMID- 12787157
TI  - Depression: its trajectory and correlates in mothers rearing children with
      intellectual disability.
AB  - BACKGROUND: Rearing a child with an intellectual disability (ID) is a lifelong
      activity, and research needs to reflect the extended nature of the task as well
      as its complexity. The present longitudinal study reports on an 11-year follow-up
      of adoptive and birth families rearing children with ID. Its focus was on
      depressive symptoms and how these changed over time in a sample of 187 mothers.
      In particular, the authors were interested in whether initial differences in
      depression between adoptive mothers who knowingly and willingly decided to rear
      their children with disabilities, and birth mothers for whom the diagnosis of
      disability was unexpected and frequently crisis-inducing, would persist over
      time. METHODS: A longitudinal method with three times of measurement provided
      data which were analysed with analysis of variance and regression techniques.
      Moreover, several other individual and family adjustment measures were examined
      with respect to their correlations with depression and an outcome variable that
      measured subjective well-being with regard to the child. Furthermore, mothers
      were classified as typical or atypical for their adoptive/birth group based on
      their depression scores at the first time of measurement. The authors predicted
      that later depression would be different based on the earlier scores. RESULTS:
      Both adoptive and birth mothers reported low depression, not significantly
      different from each other, at the 11-year follow-up. The personality variable of
      neuroticism was the strongest predictor of depression for both adoptive and birth
      mothers, accounting for 24% and 23% of the variance, respectively, but it did not
      predict the mother's subjective well-being with regard to the child. Mothers
      classified as typical or atypical for their groups at initial measurement
      continued to report significantly different depression scores 11 years later.
      CONCLUSIONS: The low depression scores, not significantly different for birth and
      adoptive mothers, portray the long-term prognosis for adjustment to rearing
      children with disabilities as primarily positive. Moreover, the predictive value
      of neuroticism suggests that general mental health is an important component
      influencing this adjustment. Nevertheless, a different pattern for a different
      outcome variable suggests that multiple measures are necessary to portray
      accurately the complexity of reaction over time.

PMID- 12787158
TI  - Stress, social support and well-being of Arab mothers of children with
      intellectual disability who are served by welfare services in northern Israel.
AB  - BACKGROUND: The present study examined the influence of a social support system
      on the level of stress and the sense of personal well-being of 100 Israeli Arab
      mothers of young children with special needs. METHODS: Fifty mothers were served
      by the welfare services in the Nazareth area while 50 did not get help on a
      regular basis. A comparison was done between educated, urban mothers, and less
      educated, rural mothers. RESULTS: The research results point to a relationship
      between informal support resources, and the marital and economic stress of the
      mothers: the higher the amount of the informal support resources, the lower the
      level of stress that was experienced by the mothers. A relationship between the
      amount of informal support and level of parental stress was not confirmed. A
      relationship between the amount of support resources and the personal well-being
      of the mothers was found: the higher the amount of informal support resources,
      the higher the sense of well-being of the mothers. A relationship between formal
      support (the welfare services), and level of stress or personal well-being was
      not found. Education and place of living were not related to level of stress or
      personal well-being. Educated mothers from urban areas used the formal support
      (the welfare services) less than less-educated mothers who lived in rural areas.
      CONCLUSIONS: The findings are interpreted with respect to practice and previous
      studies.

PMID- 12787159
TI  - Fathers of children with Down's syndrome versus other types of intellectual
      disability: perceptions, stress and involvement.
AB  - BACKGROUND: The present study examined fathers' perceptions of, stress relating
      to and involvement with children with Down's syndrome (DS) (n = 30) versus those
      with other types of intellectual disability (ID) (n = 20). METHODS: Fathers and
      mothers completed questionnaires about their children's personalities and
      maladaptive behaviours, their own parenting stress, and the fathers' level of
      involvement. RESULTS: Both fathers and mothers rated their children with DS as
      having more positive personality traits and fewer maladaptive behaviours.
      Possibly because of these positive perceptions, fathers of children with DS also
      reported less child-related stress, particularly in the areas of acceptability,
      adaptability and demandingness. The two groups of fathers were very similarly
      involved in child rearing. The personality, age and maladaptive behaviours of the
      children related to stress levels in the fathers of children with DS, while
      maladaptive behaviours, gender and the fathers' education levels related to
      stress levels in the fathers of children with other types of ID. CONCLUSIONS:
      These results highlight the importance of examining parental stress and
      involvement with children with different types of ID.

PMID- 12787160
TI  - The Family Stress and Coping Interview for families of individuals with
      developmental disabilities: a lifespan perspective on family adjustment.
AB  - BACKGROUND: The present study investigated the psychometric properties of the
      Family Stress and Coping Interview (FSCI), a questionnaire designed to
      quantitatively and qualitatively examine the experiences of parents of children
      with developmental disabilities (DDs). METHODS: The participants consisted of 106
      primary caregivers of 106 individuals with DDs from centres in Eastern, Central
      and North-western Ontario, Canada. The participants completed a demographic
      questionnaire, the FSCI, and the Vineland Adaptive Behaviour Scales. RESULTS: The
      results of this study indicate that the FSCI has adequate reliability (i.e.
      internal consistency and long-term stability) and validity (i.e. independent item
      ratings and discriminant validity). CONCLUSIONS: The results of this study
      support the use of the FSCI as a measure of family stress in research and
      practice.

PMID- 12787161
TI  - The Son-Rise Program intervention for autism: an investigation into family
      experiences.
AB  - BACKGROUND: Despite the increasing involvement of parents as therapists in
      interventions for their children with autism, research to date has focused almost
      exclusively on the outcome for the child, and little is known about the effects
      of involvement on the whole family. This is true even of highly intensive home
      based approaches such as the Son-Rise Program (SRP), the focus of the present
      paper. A longitudinal questionnaire-based study is reported which investigated a
      number of potential positive and negative effects for the family, how these
      changed over time, and their relation to child characteristics and patterns of
      intervention implementation. METHODS: Questionnaires examining family
      demographics, patterns of intervention use and perceived family effects were
      distributed three times over the course of a year to families who had attended an
      initial training course in the use of the SRP. RESULTS: The results indicated
      that, although involvement led to more drawbacks than benefits for the families
      over time, family stress levels did not rise in all cases. Few relationships were
      found between family effects and patterns of intervention use, although there was
      a strong connection with parental perceptions of intervention efficacy.
      CONCLUSIONS: The findings of the present study emphasize the need for those
      supporting families using home-based interventions to consider the needs of the
      whole family. This may be especially important if there are periods during which
      the family find the intervention to be less effective. Families embarking on such
      intensive approaches may also benefit from considering ways in which any
      disruption to family life can be minimized.

PMID- 12787162
TI  - Explaining the parental stress of fathers and mothers caring for a child with
      intellectual disability: a Double ABCX Model.
AB  - BACKGROUND: Twenty variables based on the Double ABCX Model of adaptation and
      selected on the basis of previous research were chosen to explain the parental
      stress of the mothers (n = 116) and fathers (n = 120) of children with an
      intellectual disability (age range = 1- 10 years). METHODS: Principal component
      analysis, rotated into varimax-criterion, was done separately for mothers and
      fathers. The solution containing eight factors was considered best for both
      groups. They accounted for more than 70% of the total variance of the original
      variables. These eight orthogonal components were then entered into a stepwise
      regression analysis that was done separately for mothers and fathers. RESULTS:
      The multiple regression equations obtained explained 72% of the variance in
      maternal stress and 78% of the variance in paternal stress. The equations for
      mothers and fathers contained six and seven components, respectively.
      CONCLUSIONS: The variables used in the present study were highly successful in
      accounting for parental stress. The results confirm the importance of intervening
      factors in explaining the stress. The single most important predictor of parental
      stress was the negative definition of the situation. In mothers, the negative
      definition was associated with the behavioural problems of the child while, in
      fathers it was connected with the experienced social acceptance of the child.

PMID- 12787163
TI  - The role of coping in maintaining the psychological well-being of mothers of
      adults with intellectual disability and mental illness.
AB  - BACKGROUND: Mothers who have a child with intellectual disability (ID) or mental
      illness face a lifetime of caregiving responsibilities and challenges. The
      present study investigated changes over time in how mothers cope with the
      challenges of caring for an adult child with disabilities and the effects of
      changes in coping on maternal well-being. METHODS: A sample of 246 ageing mothers
      of adults with ID and 74 mothers of adults with mental illness was drawn from two
      parallel longitudinal studies of later-life caregiving. RESULTS: There was
      considerable variability at the individual level in the degree to which mothers
      changed over time in their use of problem-focused and emotion-focused coping
      strategies. For both groups, an increase in their use of emotion-focused coping
      led to declining levels of well-being. For the parents of adults with ID, an
      increase in their use of problem-focused coping resulted in a reduction in
      distress and an improvement in the quality of the relationship with their adult
      child. For the parents of adults with mental illness, an increase in the use of
      problem-focused coping had no effect on levels of distress, but led to an
      improved relationship with their adult child. CONCLUSIONS: The present study
      underscores the importance of coping in the lives of older mothers of adults with
      disabilities.

PMID- 12787164
TI  - Influence of macrostructure of society on the life situation of families with a
      child with intellectual disability: Sweden as an example.
AB  - BACKGROUND: Most studies on families with children with intellectual disability
      (ID) have been carried out in the UK or the USA, and are influenced by the
      societal organization, and political and economic climate of those countries. In
      the USA and the UK, the care and well-being of children, with or without ID, are
      seen almost exclusively as the individual family's responsibility. In Sweden, the
      care and well-being of children are seen more as a joint responsibility. Swedish
      society has developed many privileges for all parents in order to help them care
      for their children, and the support for parents of children with disabilities is
      provided exclusively by the Government and the community. The overall question
      explored in this descriptive, quantitative and qualitative study was: Are
      families in Sweden experiencing the stressors and life situations described in
      the studies of parents in more individualistic societies? METHODS: Two hundred
      and twenty-six families with children with ID and 234 control families with
      children ranging from 0 to 16 years of age answered mail surveys. RESULTS: Taken
      together, parents in Sweden describe most of the stressors proposed in the
      international literature with the exception of financial strain. Restricted
      social life and time restrictions seem to be the two most evident and bothersome
      stressors for Swedish families with children who have ID. CONCLUSIONS: As in
      previous research, the parents of children with ID and autism experienced more
      stressors and restrictions in their lives than the parents of children with DS
      and control families.

PMID- 12787165
TI  - Supporting families over the life course: mapping temporality.
AB  - BACKGROUND: The present paper addresses a rather neglected dimension of family
      caregiving, its temporality. Many accounts of caregiving assume a state of
      stasis, and therefore, overlook factors which shape the evolving experience of
      family caregiving over the life course. METHODS: The paper begins by offering
      some reflections on theoretical and methodological issues identified by life
      course researchers. RESULTS: Based both on theoretical propositions and a growing
      body of empirical evidence, this paper offers a heuristic for thinking about
      caregiving stages applied to families supporting people with intellectual
      disability. CONCLUSIONS: This heuristic is used to suggest further avenues of
      research and development.

PMID- 12787166
TI  - Management of respite and personal assistance services in a consumer-directed
      family support programme.
AB  - BACKGROUND: The present study explores the management of respite and personal
      assistance services by families with relatives with developmental disability
      (DD). It focuses on the control of families over recruiting, hiring, training,
      scheduling, directing and negotiating wages of the staff they hire to provide
      services. METHODS: Surveys from 97 families using paid respite or personal
      assistance services were used to test associations between: 1) level of control
      of services and outcome variables; 2) hiring relatives to provide services and
      outcome variables. RESULTS: More control by families in the management of their
      respite/personal assistance services was associated with increased service
      satisfaction, increased community involvement of individuals with DD and
      increased employment of mothers. Families tended to hire friends, neighbours, and
      to a great extent, other family members. Hiring of other relatives to provide
      services was associated with the increased community involvement of individuals
      with DD. CONCLUSIONS: The present study supports the idea that there are benefits
      for both caregivers and individuals with DD with increased control of respite and
      personal assistance services. The study also supports benefits associated with
      hiring relatives and recommends additional research in this area to guide
      policies.

PMID- 12787167
TI  - Toward assessing family outcomes of service delivery: validation of a family
      quality of life survey.
AB  - BACKGROUND: The concept of family quality of life (QoL) has emerged as an
      important outcome of service delivery for individuals with disabilities and their
      families. The present study describes the process of developing a tool to measure
      family QoL. METHODS AND RESULTS: A total of 1197 respondents participated in a
      national field test. Through factor analysis, the survey was refined in several
      ways: (1) the preliminary 10-domain structure was reduced to a five-domain
      structure; (2) a total of 41 items were selected for the revised survey; and (3)
      wordings were clarified. CONCLUSIONS: The implications for future research and
      practice are discussed.

PMID- 12787168
TI  - Mothers of children and adolescents with intellectual disability: social and
      economic situation, mental health status, and the self-assessed social and
      psychological impact of the child's difficulties.
AB  - BACKGROUND: Few large-scale studies with well-constructed samples have compared
      the socio-economic circumstances and social impact of raising a child with
      intellectual disability (ID). The aims of the present paper were to: (1) compare
      the socio-economic situation of mothers raising a child with ID to that of
      mothers of non-ID children; (2) assess the contribution of raising a child with
      ID to negative psychological outcomes for mothers; and (3) identify variables
      associated with negative psychological outcomes among mothers of children with
      ID. METHODS: The 1999 Office for National Statistics survey, Mental Health of
      Children and Adolescents in Great Britain, 1999, collected information on a
      multistage stratified random sample of 10 438 children between 5 and 15 years of
      age across 475 postal code sectors in England, Scotland and Wales. Secondary
      analysis was undertaken of the social and economic circumstances, and stress
      reported by 245 mothers of sampled children with ID and a comparison group of 9
      481 mothers of sampled children who did not have ID. RESULTS: The results
      indicate that: (1) families supporting a child with ID were significantly
      economically disadvantaged when compared with families supporting a child who did
      not have ID; (2) when compared with mothers of sampled children who did not have
      ID, mothers of sampled children with ID reported that their child's difficulties
      resulted in greater social and psychological impact; (3) having a child with ID
      marginally reduced the odds of mothers screening positive for having mental
      health problems (once all other variables were taken into account); and (4) among
      mothers of children with ID, mental health problems were associated with the
      child's difficulties having a greater social impact, having a boy, the child
      experiencing more than one potentially stressful life event, poverty, receipt of
      means-tested welfare benefits and 'unhealthy' family functioning. CONCLUSIONS:
      These results highlight the importance of combating poverty among children with
      ID and their families, and the need to develop more complex models of
      understanding and intervention.

PMID- 12787170
TI  - Current thinking in the evidence-based health care debate.

PMID- 12787171
TI  - A critical appraisal of evidence-based medicine: some ethical considerations.
AB  - Evidence-based medicine (EBM) is a concept that has grown to dominate the medical
      literature over the last decade. EBM has provoked a variety of criticisms,
      scientific, philosophical and sociological. However, while its basic conclusion-
      that we should practise EBM--is ethical, there has been limited ethical analysis
      of EBM. This paper aims to provide an analysis of EBM from an ethical perspective
      and identify some of EBM's potential ethical implications. Following a
      description of what constitutes EBM, this paper will identify and assess some of
      the basic values and epistemological assumptions of EBM that provide support for
      the moral duty to practise EBM. It will then examine potential ethical
      implications that could arise from practising EBM, given the challenges that have
      been made of EBM's assumptions and claims to authority. This paper will conclude
      by arguing that practitioners could strengthen the ethics of EBM by embracing a
      broader definition of evidence and including ethical criteria in the critical
      appraisal of research studies.

PMID- 12787172
TI  - Commentary on 'A critical appraisal of evidence-based medicine: some ethical
      considerations' (Gupta 2003; Journal of Evaluation in Clinical Practice 9, 111
      121).

PMID- 12787173
TI  - The paradox of evidence-based medicine. Commentary on Gupta (2003), A critical
      appraisal of evidence-based medicine: some ethical considerations. Journal of
      Evaluation in Clinical Practice 9, 111-121.

PMID- 12787174
TI  - On morality and logic in medical practice: commentary on 'A critical appraisal of
      evidence-based medicine: some ethical considerations' (Gupta 2003; Journal of
      Evaluation in Clinical Practice 9, 111-121).

PMID- 12787175
TI  - An objectivist's view on the ethics of evidence-based medicine: commentary on 'A
      critical appraisal of evidence-based medicine: some ethical considerations'
      (Gupta 2003; Journal of Evaluation in Clinical Practice 9, 111-121).

PMID- 12787177
TI  - Evaluation of screening for a cancer: annotated catechism of the Gold Standard
      creed.
AB  - Even non-scientific people are generally aware of, and commonly also personally
      affected by, the confusion and debates that arose from two recent systematic
      reviews and their associated meta-analyses of the published randomized controlled
      trials (RCTs) that had been designed to assess the usefulness of screening for
      breast cancer. With nothing about the principles of research on cancer screening
      learned from this debacle, an RCT on screening for lung cancer has just been
      launched in the same 'gold standard' framework; and so in about 10 years, and
      upon expenditure of hundreds of millions of dollars, we are said to be able to
      learn whether the screening saves lives and whether it thereby is justifiable as
      a matter of public policy. We here examine the core tenets and precepts in this
      'gold standard' line of thinking, and we argue that they are matters of belief at
      variance with the dictates of reason.

PMID- 12787178
TI  - Generalizability: beyond plausibility and handwaving.
AB  - The question of how we apply knowledge from biomedical science to medical and
      public health practice has been the subject of heated debates about
      generalizability and related concepts, such as applicability and inductive
      inference. In this essay, I interpret the term from the perspective of two causal
      models: determinism and indeterminism. I suggest that theories of
      generalizability can be formulated on the basis of both models and take the form
      of testable but unverifiable hypotheses, an attribute that is common to all
      scientific theories. Nonetheless, there is one noteworthy difference between the
      two models: determinism allows one to rationalize a decision to treat a certain
      kind of patient but only indirectly a decision to treat any particular patient,
      whereas indeterminism accommodates both types of decisions.

PMID- 12787179
TI  - Inductive reasoning in medicine: lessons from Carl Gustav Hempel's 'inductive
      statistical' model.
AB  - The purpose of this paper is to discuss both the fundamental requirements of
      sound scientific explanations and predictions and common fallacies that occur in
      explaining and predicting medical problems. To this end, the paper presents Carl
      Gustav Hempel's 'covering-law' model (1948 and 1962) and reviews some of the
      criticism of the model. The strength of Hempel's model is that it shows that
      inductive arguments, when applied with the requirement of maximal specificity,
      can serve as explanations as well as predictions. The major weakness of the
      'covering-law' model, its inability to portray causal relatedness, has been
      addressed by philosophers such as Wesley Salmon. While few philosophers today
      agree with the 'covering-law' model in its original formulation, there is
      widespread consensus that the law has made a central contribution to describing
      the fundamental requirements of sound scientific explanations. Applying this
      model and its revisions in the medical context may help uncover potentially
      undetected fallacies in reasoning when explaining and predicting medical
      problems.

PMID- 12787180
TI  - Non-linearity in clinical practice.
AB  - The whole spectrum of medicine consists of complex non-linear systems that are
      balanced and interact with each other. How non-linearity confers stability on a
      system and explains variation and uncertainty in clinical medicine is discussed.
      A major theme is that a small alteration in initial conditions may have a major
      effect on the end result. In the context of non-linearity, it is argued that
      'evidence-based medicine' (EBM) as it exists today can only ever be relevant to a
      small fraction of the domain of medicine, that the 'art of medicine' consists of
      an intuitive 'tuning in' to these complex systems and as such is not so much an
      art as an expression of non-linear science. The main cause of iatrogenic disease
      is interpreted as a failure to understand the complexity of the systems being
      treated. Case study examples are given and analysed in non-linear terms. It is
      concluded that good medicine concerns individualized treatment of an individual
      patient whose body functions are governed by non-linear processes. EBM as it
      exists today paints with a broad and limited brush, but it does promise a fresh
      new direction. In this context, we need to expand the spectrum of scientific
      medicine to include non-linearity, and to look upon the 'art of medicine' as a
      historical (but unstated) legacy in this domain.

PMID- 12787181
TI  - Evaluating and synthesizing qualitative research: the need to develop a
      distinctive approach.
AB  - The growing popularity of qualitative research has led to calls for it to be
      incorporated into the evidence base. It is argued that, in seeking to respond to
      this challenge, it is important that we recognize the important differences
      between qualitative and quantitative research and that we take this into account
      in developing a distinctive approach. This paper outlines the distinctive
      contribution made by qualitative research with regard to the nature of the
      curiosity involved, the iterative research process and its treatment of data,
      analysis and findings. We caution against simply importing templates developed
      for systematic review of quantitative work, and make suggestions with regard to
      developing a new model for evaluating and synthesizing qualitative work. The
      proposed new model takes a critical look at some of the assumptions underpinning
      systematic review, such as the process of literature searching and selection of
      relevant material. Although there is potential for checklist items--such as
      purposive sampling, respondent validation, multiple coding, triangulation and
      grounded theory--to be used over-prescriptively in evaluating qualitative papers,
      it is argued that a more creative engagement with these concepts could yield a
      distinctive approach more appropriate for this type of work. Moreover, we
      speculate that some of the questions thereby raised might be usefully applied to
      consideration of established procedures for reviewing quantitative work.

PMID- 12787182
TI  - Reframing the evaluation of qualitative health research: reflections on a review
      of appraisal guidelines in the health sciences.
AB  - In this article, we explore the form of evaluation put forward by guidelines used
      in the health sciences for appraising qualitative research and we begin to
      articulate an alternative posture. Most guidelines are derivative of the modes of
      assessment developed by clinical epidemiologists as part of the promotion of
      evidence-based medicine (EBM). They are predominantly proceduralist in
      orientation, equating quality with the proper execution of research techniques.
      We argue that this form of judgment assumes a fixed relationship between research
      practice and knowledge generated, and tends to over-simplify and standardize the
      complex and non-formulaic nature of qualitative inquiry. A concern with methods
      as objects of judgment in and of themselves restricts the reader's field of
      vision to the research process and diverts attention away from the analytic
      content of the research. We propose an alternative 'substantive' perspective that
      focuses on the analysis put forward, and regards methods as resources for
      engaging with and understanding the substantive findings and topic of inquiry. An
      important challenge is to find a way to embody such a form of judgment in
      practical assessment tools.

PMID- 12787183
TI  - The state of the science and art of practice guidelines development,
      dissemination and evaluation in Canada.
AB  - The Canadian Medical Association (CMA) maintains a database of clinical practice
      guidelines (CPGs) developed or endorsed by Canadian organizations. The study
      purpose was to describe how these guidelines were developed, disseminated and
      evaluated. A survey was mailed to the developer of each CPG registered in the CMA
      Infobase between June 1996 and December 1999. Data were received for 730 unique
      guidelines (response rate of 70%) developed by 75 organizations. Of these, 72%
      were developed by committees that had a formal process for selecting their
      members. The scientific literature was reviewed for all of the guidelines, a
      computerized search undertaken for 88% and the search strategy included 34% of
      CPG documents. An attempt was made to grade the quality of the evidence
      underpinning 54% of the guidelines. For most guidelines, consensus about values
      or judgements was reached by expert opinion through open discussion (78% of
      guidelines). The most common strategies used to disseminate the guidelines were
      direct mailing of guidelines to members of the developing organization (80% of
      all guidelines), publishing guidelines in newsletters/journals (76%), direct
      mailing to others (73%), electronic dissemination (62%), educational or
      continuing medical education activities (50%), and providing information about
      guidelines to patients/consumers (47%). Overall, 5% of the guidelines have been
      evaluated to determine their impact on health outcomes. During the 5-year study
      period (1994-99), the more recent guidelines were more likely to use
      multidisciplinary development panels, report the literature search strategies and
      grade the quality of the evidence. The CPG development process in Canada is
      becoming more rigorous and reproducible, but there is still considerable room for
      improvement. In addition to encouraging Canadian guideline developers to use more
      rigorous and transparent methods, considerably more attention must be focused on
      using and identifying effective and cost-effective strategies to promote and
      facilitate the uptake of guidelines by practitioners and to evaluate the impact
      of guidelines on patient outcomes.

PMID- 12787184
TI  - The impact of stroke practice guidelines on knowledge and practice patterns of
      acute care health professionals.
AB  - RATIONALE, AIMS AND OBJECTIVES: The Agency for Healthcare Research and Quality's
      Post-Stroke Rehabilitation Guidelines were developed to improve the quality,
      appropriateness and effectiveness of rehabilitation practices. An important goal
      of the guidelines process is to disseminate information to practitioners in order
      to encourage adoption of effective practices. To date, no systematic evaluation
      of these guidelines has been completed, nor has a programme been designed to
      evaluate the effectiveness of an educational programme about the guidelines. The
      objective was to evaluate changes in knowledge and practice following
      presentation of a lecture-based, educational programme about post-stroke
      rehabilitation guidelines. METHODS: The research design was a single group, pre
      test-post-test design without a comparison group. A knowledge and referral
      practices questionnaire was developed specifically for this study. RESULTS:
      Lecture attendance was not associated with an increase in knowledge or referrals.
      However, we found that respondents who made more referrals at follow-up had a
      higher knowledge level at pre-test. Also, those who completed a follow-up
      assessment knew more about the guidelines at the initial assessment than did
      those who did not complete the follow-up assessment. In addition, doctors knew
      more about stroke rehabilitation than the non-doctors, both at the pre-test and
      follow-up. DISCUSSION AND CONCLUSIONS: Encouraging behaviour change among doctors
      and allied health professionals in referrals and clinical practice is a
      complicated process. Providing individual follow-up and lengthier contacts,
      assuring that care providers receive high-quality evidence that guidelines
      improve care, and consulting with key decision-makers about guideline
      implementation might enhance behaviour change.

PMID- 12787185
TI  - Seeking evidence from medical research consumers as part of the medical research
      process could improve the uptake of research evidence.
AB  - Concerns have been expressed about gaps between available medical research
      evidence and current medical practice. These gaps have been attributed to process
      problems with the implementation of evidence previously judged to be appropriate,
      rather than to problems with the appropriateness of the evidence provided for
      implementation. Two such 'appropriateness' problems are the applicability of
      research evidence to an individual patient, and the acceptability to an
      individual patient of a proposed treatment. Part of both these problems is due to
      the pre-eminence of the scientific paradigm within the medical research domain,
      and of the randomized controlled clinical trial within that domain. However,
      there is an opportunity beneficially to address both these problems by supporting
      reciprocal communication between medical research 'producers' and medical
      research 'consumers'--both practising clinicians and patients' representatives-
      in the setting of research priorities, selection of topics for research,
      development of research questions and study designs, in-progress reviewing, and
      final reporting of medical research projects. Such communication could allow
      researchers to understand, and respond to, clinicians' and patients' inputs
      concerning the applicability, utility and acceptability issues that will
      ultimately affect whether, and how, medical research findings can be applied.
      Such communication could also assist with some post-research implementation
      issues: integration of appropriate evidence into everyday practice; access to
      appropriate information sources; and a critical lack of necessary time.

PMID- 12787186
TI  - Achieving change in health care practice.
AB  - This study evaluated a practice development programme consisting of nine projects
      together known as STEP (South Thames Evidence-Based Practice Project). The aim of
      STEP was to establish and assess evidence-based practice in nursing and other
      health care practice areas. Objectives of the independent evaluation were to
      identify and assess outcomes from the process of change and investigate the
      association between these intermediate outcomes and patient outcomes. Outcomes
      were measured before and after the changes were introduced. Data collection
      methods included interviews with the change agents and other stakeholders, and a
      questionnaire to staff in each centre. Patient outcome data were collected from
      each centre. The findings revealed 'dissemination' of information to staff and
      'adherence' by staff to new practice guidelines to be important intermediate
      outcomes in the process of change. The need emerged for a supportive
      organizational culture and commitment, recognition of the importance of change
      and a credible change agent. There was some evidence of linearity in the process
      of change in that a logical route appeared from dissemination of information to
      staff through adherence to the change guidelines to improvement in patient
      outcome in six of the nine centres. Linearity was less apparent in the other
      three centres, where the process of change seemed more dynamic and chaotic. These
      three centres were affected more than the others by organizational barriers to
      change. Our conclusions support the view that the linear model of change can work
      in settings with high levels of certainty but complexity theory is more likely to
      underpin the process of change in organizations characterized by uncertainty.

PMID- 12787188
TI  - The evolution of clinical audit as a tool for quality improvement.
AB  - Clinical auditing practices are recognized universally as a useful tool in
      evaluating and improving the quality of care provided by a health service.
      External auditing is a regular activity for mental health services in Australia
      but internal auditing activities are conducted at the discretion of each service.
      This paper evaluates the effectiveness of 6 years of internal auditing activities
      in a mental health service. A review of the scope, audit tools, purpose, sampling
      and design of the internal audits and identification of the recommendations from
      six consecutive annual audit reports was completed. Audit recommendations were
      examined, as well as levels of implementation and reasons for success or failure.
      Fifty-seven recommendations were identified, with 35% without action, 28%
      implemented and 33.3% still pending or in progress. The recommendations were more
      likely to be implemented if they relied on activity, planning and action across a
      selection of service areas rather than being restricted to individual departments
      within a service, if they did not involve non-mental health service departments
      and if they were not reliant on attitudinal change. Tools used, scope and
      reporting formats have become more sophisticated as part of the evolutionary
      nature of the auditing process. Internal auditing in the Barwon Health Mental
      Health Service has been effective in producing change in the quality of care
      across the organization. A number of evolutionary changes in the audit process
      have improved the efficiency and effectiveness of the audit.

PMID- 12787187
TI  - Evaluating change in health care practice: lessons from three studies.
AB  - Implementation and evaluation of evidence-based practice are high on the policy
      agenda in the UK National Health Service. Over the last 30 years evaluation of
      practice in the health services has moved from a (medical) profession-led mode to
      a politically and managerially led mode in which objectives are pre-set by those
      who legitimate and fund the services. Against this background we describe three
      recent evaluations of nursing practice as examples to illustrate challenges
      encountered when evaluating changes in practice developments in health care. If
      evaluations are to contribute to improvements in practice, a shift is needed from
      an over-reliance on one-off outcome evaluations to those that have a cumulative
      component and take account of context and process as well as outcome. The merits
      of realistic evaluation are suggested as a solution to the methodological
      limitations of traditional approaches and to developing generalizable theory.

PMID- 12787189
TI  - The Australian Centre for Evidence-based Clinical Practice generic audit tool:
      Auditmaker for health professionals.
AB  - Audit is an important step in the process of health care evaluation and quality
      improvement. Some of the barriers to audit include the lack of support in
      initiating an audit, difficulty with data collection and lack of time. Auditmaker
      is a computer package that guides the clinician through the initial process of
      designing an audit, choosing factors and outcomes to analyse, then provides
      customizable data entry forms, and finally simple reports summarizing the data.
      It has user-friendly features, such as help buttons, drop-down lists and built in
      comorbidities and outcomes of common interest. It provides a generic tool for
      performing an audit as well as providing an opportunity for different clinicians
      in different institutions or practice settings to perform similar audits using
      the same data collection tool, which can provide the basis of benchmarking.
      Auditmaker is available for downloading from the ACEPBCP website:
      http://www.acebcp.org.au.

PMID- 12787190
TI  - Are performance indicators generic? The international experience of the Quality
      Indicator Project.
AB  - Performance indicators for healthcare organizations represent a strategy for
      accountability worldwide. A universal approach to either the design for
      indicators or their applicability to local needs remains a work in progress. The
      Maryland Hospital Association's Quality Indicator Project (QIP) is the only
      indicator-based performance measurement system used worldwide. This paper
      presents, for the first time in QIP's 17 years of existence, data showing why
      MHA's QIP may qualify as the most accepted generic methodology for healthcare
      performance measurement and evaluation.

PMID- 12787191
TI  - Public disclosure of comparative clinical performance data: lessons from the
      Scottish experience.
AB  - There is growing international interest in making information available on the
      clinical quality and performance of health care providers. In the United States
      of America, where public reporting is most advanced, comparative performance
      information in the form of 'report cards', 'provider profiles' and 'consumer
      reports' has been published for over a decade. In Europe, Scotland has been at
      the forefront of releasing clinical performance data and has disseminated such
      information since 1994. This paper reviews the Scottish experience of public
      disclosure and distils the key lessons for other countries seeking to implement
      similar programmes. It is based on the findings of the first empirical evaluation
      of a national clinical reporting initiative outside the United States. The study
      examined the impact of publication of Scottish (CRAG) clinical outcome indicators
      on four key stakeholder groups: health care providers, regional government health
      care purchasers, general practitioners and consumer advocacy agencies. We
      conclude that those responsible for developing clinical reporting systems should
      not only pay close attention to developing technically valid and professionally
      credible data which are tailored to the information needs of different end users,
      but should also focus on developing a suitable incentive structure and
      organizational environment that fosters the constructive use of such information.

PMID- 12787192
TI  - Evidence-based practice in mental health: practical weaknesses meet political
      strengths.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Evidence-based medicine (EBM) has given rise to
      evidence-based practice (EBP) in the field of mental health. EBP too is
      predicated on an evidence hierarchy and has the goal of using the "best evidence"
      (usually randomized controlled trials) to improve practice. EBP is increasingly
      influential in mental health care in the U.S. Growing numbers of researchers and
      public officials endorse its claims and pursue its benefits. The rationale for
      this paper is to examine the potential of EBP for the field of mental health-and
      public mental health care specifically. Is it likely to contribute to improved
      lives for mentally ill people? If so, how? METHODS: This qualitative study relies
      on archival, and to a much lesser extent, informant interview data. Informants
      were mostly public mental health officials because they are in a position to
      implement EBP on a large scale and their policies are a matter of public record.
      Interviews were semi-structured, held in person and on the telephone, and lasted
      one to two hours. Archival research included the substantial literature on EBM
      and EBP plus studies and articles on the practice and policy of U.S. public
      mental health care. RESULTS: The results of this study were that there exists an
      extensive, coherent literature critical of EBM and of EBP specifically. Attempts
      to implement EBP will falter on epistemological and organizational barriers.
      Still, as a public idea--that more science will bring about better mental health
      practice--EBP may well serve political purposes, especially in the U.S. public
      mental health system, where more overtly ideological policies have been
      inadequate in the past. EBP, as a public idea, has the advantage of ambiguity,
      accountability, quantifiability, etc. CONCLUSIONS: This paper concludes that EBP
      is growing more influential in public mental health care in the U.S. Its
      practical strengths, i.e., its improvement of mental health practice, may turn
      out to be less than its strengths as a public idea in the formulation and
      dissemination of mental health policy.

PMID- 12787194
TI  - Improving oral health: current considerations.
AB  - The high incidence of periodontal disease among adults in the Western world
      indicates that in most cases, routine dental care could be considerably improved.
      The progressive effect of the disease suggests that improvements in oral
      cleanliness are mandatory if large numbers of adults are to retain their teeth
      into old age. Data show that periodontal disease can be minimized through
      effective plaque control, and that a combination of brushing, interdental
      cleaning, and chemotherapeutic agents (e.g. mouthwash) is beneficial to patients
      with plaque control problems. The vast majority of adults do not follow an
      adequate home-care routine. Average brushing times are low, and only a minority
      of patients regularly floss. In addition, in those patients who do regularly
      brush and floss, a deterioration of plaque control occurs over time, suggesting
      that compliance is a major issue. The principal challenge for dental
      professionals is to identify how best to elicit an improvement.

PMID- 12787195
TI  - Recent concepts in plaque formation.
AB  - Dental plaque is an adherent, bacterial film, and is the main pathological agent
      for periodontal diseases. The formation of dental plaque can occur both
      supragingivally and subgingivally. The development of plaque is a three-step
      process. Following the formation of a pellicle, pioneer micro-organisms will
      adhere to it, proliferate and form colonies. The final stage involves the
      aggregation of filamentous organisms and spirochetes into a cohesive biofilm.
      Many products of the plaque bacteria reach the subepithelial tissue, causing
      inflammatory responses such as increased vascularity and leukocyte diapedesis.
      Both supragingival and subgingival plaque may form a hard, mineralized mass
      called calculus. The surface of calculus harbours bacteria, which may exacerbate
      the inflammatory responses. An effective oral antiseptic must be active against a
      wide range of Gram-positive and Gram-negative bacterial species, including
      streptococci and fusobacteria. Ideally, an effective agent would also penetrate
      the plaque biofilm. Data show that essential oil and chlorhexidine mouthwashes
      have the broadest antimicrobial effects.

PMID- 12787196
TI  - Penetrating the plaque biofilm: impact of essential oil mouthwash.
AB  - The interaction between saliva-coated tooth surfaces and pathogenic bacteria is
      partly governed by electrostatic and hydrophobic interactions, providing a solid
      rationale for using chemical agents as part of a plaque-control routine.
      Chlorhexidine works in several ways. For example, it binds to salivary mucins on
      the bacterial cell membrane, and penetrates the plaque biofilm. Essential oil
      (EO) mouthwashes kill micro-organisms by disrupting their cell walls and
      inhibiting their enzymic activity. They prevent bacterial aggregation, slow
      multiplication and extract endotoxins. Recent studies have shown that bacterial
      phenotypes are altered when organisms change from a planktonic to a sessile
      state. This suggests that an effective mouthwash must also penetrate the plaque
      biofilm. Two studies have demonstrated the ability of an EO mouthwash to
      penetrate the plaque biofilm.

PMID- 12787198
TI  - Management of oral malodour.
AB  - Halitosis is a common problem. Its aetiology is multifactorial, but oral malodour
      is usually caused by microbial metabolism from the tongue, saliva or dental
      plaque. Mouthwashes are only effective against halitosis caused by intraoral
      factors. The principal causative agents of oral malodour are volatile sulphide
      compounds (VSCs), including hydrogen sulphide, methyl mercaptan and dimethyl
      sulphide. Data suggest that oral VSC levels correlate with the depth of
      periodontal pockets. Trials have shown that both mechanical oral care and
      mouthwash use can reduce halitosis levels. The majority of studies involving
      mouthwashes have investigated chlorhexidine and essential oil mouthwashes,
      although comparative studies are sparse.

PMID- 12787197
TI  - Evidence-based control of plaque and gingivitis.
AB  - Most adults brush and floss inadequately, and constant education and/or
      reinforcement is often required. Bacteria are usually left behind with mechanical
      oral health routines, and chemotherapeutic agents may have a key role as adjuncts
      to daily home-care. To date, two antiseptic mouthwashes have received the ADA
      Seal of Acceptance: Peridex (Zila Pharmaceuticals, Phoenix, AZ, USA; CHX,
      chlorhexidine) and Listerine (Pfizer Consumer Healthcare, Morris Plains, NJ, USA;
      essential oil (EO) mouthwash). CHX has a strong affinity for tooth and tissue
      surfaces, but can cause brown staining on the teeth and tongue. Patients must
      also wait until all traces of toothpaste are removed before rinsing with CHX.
      Long-term use of an EO mouthwash is microbiologically safe, with no changes
      observed in the bacterial composition of supragingival plaque, and no evidence of
      antimicrobial resistance. A number of trials have demonstrated the long-term
      plaque- and gingivitis-reducing properties of both CHX and EO mouthwashes. These
      studies clearly demonstrate that these agents have lasting efficacy, and can
      access hard-to-reach areas.

PMID- 12787199
TI  - Additional properties and uses of essential oils.
AB  - Much evidence has been published supporting the use of mouthwashes in a number of
      crucial areas of oral health. These areas include antibacterial activity, home
      irrigation, maintenance of implant health, postsurgery uses, reduction of
      bacteria in dental aerosols and bacteraemia reduction. Although other commonly
      used mouthwashes (e.g. chlorhexidine) have been reviewed in other articles in
      this Supplement, this article concentrates solely on data supporting essential
      oil mouthwash use in these oral health areas.

PMID- 12787201
TI  - Periodontal Practice. Fourth European Workshop on Periodontology. Charterhouse at
      Ittingen, Thurgau, Switzerland. February 2-4, 2002.

PMID- 12787200
TI  - Essential oil mouthwashes: a key component in oral health management.
AB  - This Supplement provides clear evidence that essential oil (EO) mouthwashes can
      be a beneficial, safe component of daily oral health routines. However, despite
      the wealth of supporting evidence, several issues are worthy of discussion.
      Patient compliance is a clear issue with oral home-care routines, and the
      emphasis is on dental professionals to communicate the importance of adherence.
      The reasons for each step of the oral-care routine (i.e. brushing, flossing,
      rinsing) should be clearly explained, and if required, additional motivation
      should be provided. Most mouthwashes contain denatured alcohol as a delivery
      vehicle, and some concern has been raised about the association of alcohol with
      oral cancer. However, a review by the Food and Drug Administration and American
      Dental Association found that the supporting evidence to date is inconsistent and
      contradictory. Some mouthwashes have a pH below 5.5, and some researchers believe
      that this can lead to tooth erosion. Studies have shown that although the pH of
      an EO mouthwash is below 5.5, salivary pH remains above 5.5 following rinsing and
      for 15 min postrinse.

PMID- 12787202
TI  - A guide to systematic reviews.
AB  - Systematic reviews have become widely used for evaluating evidence across all
      fields of biomedicine. The objective of a systematic review is to provide a
      comprehensive and contemporary appraisal of research using transparent methods
      whilst aiming to minimize bias. In essence, research methodology is employed in
      the conduct of the review. Such reviews are therefore fundamentally different
      from traditional 'narrative' review articles in their purpose and in their
      potential to aid clinical decision-making. This paper is a guide to the rationale
      and nature of systematic reviews and will provide a background to understanding
      their use in clinical practice.

PMID- 12787204
TI  - Is periodontitis associated with an increased risk of coronary heart disease and
      preterm and/or low birth weight births?
AB  - The objective of this systematic review was to determine whether periodontal
      disease is associated with an increased risk for coronary heart disease (CHD) and
      preterm and/or low birth weight deliveries (PLBW). A literature search was
      performed to identify cross-sectional, case-control, and cohort studies as well
      as clinical trials addressing different aspects of periodontal disease (clinical,
      microbial, immunological) and clinical outcomes of CHD or PLBW. The periodontitis
      CHD association was evaluated in eight cohort, four case-control- and four cross
      sectional studies. Meta-analysis was not performed due to the extensive
      heterogeneity of the studies, particularly with regard to periodontitis measures,
      which varied from full mouth probing assessments to questionnaires. Percentage
      wise, 50% of the cohort studies (4/8), 75% of the case-control studies (3/4) and
      50% of the cross-sectional studies (2/4) reported a significant association
      between clinical measures of periodontitis and CHD (excess risk ranged from 0 to
      3.3-fold). The periodontitis-PLBW association was evaluated in one cohort and two
      case-control studies. The cohort study as well as one of the two case-control
      studies reported a significant association between periodontitis and PLBW (odds
      ratios 4.4-7.9). From two additional case-control studies microbiological data
      could be extracted. Bacteroides forsythus was found to be associated with PLBW in
      both studies. In conclusion, the evidence linking periodontitis with an increased
      risk for CHD and PLBW is limited. There is a clear need for new, well designed
      observational and intervention studies to confirm the thus far observed
      associations, explore the validity of the associations in diverse populations,
      establish whether they are causal in nature and determine potential benefits of
      periodontal intervention in reducing the risk for these conditions.

PMID- 12787203
TI  - Can presence or absence of periodontal pathogens distinguish between subjects
      with chronic and aggressive periodontitis? A systematic review.
AB  - OBJECTIVES: The purpose of this study was to determine to what extent the
      presence or absence of periodontal pathogens can distinguish between subjects
      with chronic and aggressive periodontitis. MATERIAL AND METHODS: A systematic
      review of cross sectional and longitudinal studies providing microbiological data
      both from patients with chronic periodontitis (ChP) and aggressive periodontitis
      (AgP) at a subject level. Strict inclusion criteria were applied. The presence or
      absence of five microorganisms was selected as primary study parameters:
      Actinobacillus actinomycetemcomitans (AA), Porphyromonas gingivalis (PG),
      Prevotella intermedia (PI), Bacteroides forsythus (BF), and Campylobacter rectus
      (CR). RESULTS: The presence or absence of AA could be evaluated in 11 papers. In
      seven papers the presence or absence of PG could be analysed. Subject specific
      data on PI were available from six studies. Two studies could be used regarding
      the presence or absence of BF, and two regarding CR. Sensitivity and specificity
      of every microbiological test were individually calculated for each selected
      study, assuming that the clinical diagnosis of AgP or ChP was the true status the
      tests attempted to detect. AgP was considered to be the condition of interest and
      ChP was considered equivalent to 'non-AgP'. Receiver Operator Characteristic
      (ROC) diagrams were constructed using these data. ROC diagrams indicated the
      limited discriminatory ability of all of the test parameters to identify subjects
      with AgP. An additional assessment showed that the highly leukotoxic variant of
      AA was uniquely associated with patients suffering from aggressive periodontitis.
      However, in a high proportion of patients diagnosed with AgP the presence of this
      variant could not be detected. CONCLUSION: The presence or absence of AA, PG, PI,
      BF or CR could not discriminate between subjects with AgP from those with ChP.

PMID- 12787206
TI  - A systematic review of powered vs manual toothbrushes in periodontal cause
      related therapy.
AB  - BACKGROUND: Power-driven toothbrushes (PDT) have been designed to improve the
      efficacy of oral hygiene. It is not clear how they compare in efficacy with
      manual toothbrushes in cause-related periodontal therapy. OBJECTIVES: To evaluate
      the effectiveness of the use of a PDT as compared with a manual toothbrush (MT),
      in terms of gingival bleeding or inflammation resolution, in cause-related
      periodontal therapy. MATERIAL AND METHODS: An electronic (MEDLINE and Cochrane
      Oral Health Group Specialised Trials Register) and a manual search were made to
      detect studies which permitted the evaluation of the efficacy of PDT in the
      reduction of gingival bleeding or inflammation, and their effect on other
      secondary variables. Only randomized studies in adults, published in English up
      to June 2001, which compared a PDT with an MT, and evaluated the evolution of
      gingival bleeding or inflammation were included. The selection of articles,
      extraction of data and assessment of validity were made independently by several
      reviewers. RESULTS: Twenty-one studies were finally selected. The heterogeneity
      of the data prevented a quantitative analysis. A higher efficacy in the reduction
      of gingival bleeding or inflammation in the PDT patients was detected in 10
      studies. This effect appears to be related to the capacity to reduce plaque, and
      is more evident in counter-rotational and oscillating-rotating brushes. No solid
      evidence was found for a higher efficacy of sonic brushes. In short-term studies
      with prophylaxis after initial examination, independently of the type of PDT
      tested, no significant differences were found. CONCLUSION: The use of PDT,
      especially counter-rotational and oscillating-rotating brushes, can be beneficial
      in reducing the levels of gingival bleeding or inflammation. There is a need for
      methodological homogeneity in future studies in this field to enable quantitative
      analysis of their results.

PMID- 12787207
TI  - A systematic review on the clinical efficacy of subgingival debridement in the
      treatment of chronic periodontitis.
AB  - OBJECTIVE: The purpose of this study was to perform a systematic review of the
      literature and to evaluate, in patients with chronic periodontitis, what the
      effect is of subgingival debridement (SGD), in terms of bleeding on probing,
      pocket depth and probing attachment level. MATERIAL AND METHODS: An electronic
      search of the Cochrane Oral Health Group specialized register and MEDLINE were
      performed using specific search terms to identify studies assessing in patients
      with chronic periodontitis the effect of subgingival debridement with regard to
      clinical outcomes. This was performed on titles registered up to 2001. The only
      papers included were those which utilized data based on the patient as unit of
      observation. RESULTS: The searches identified 702 abstracts. Titles and abstracts
      were independently screened by two reviewers (G.A.W. & M.F.T.) to identify
      publications that met specific inclusion criteria. The agreement between the two
      reviewers was assessed. The kappa score for agreement was 0.80. Review of these
      abstracts resulted in 114 publications for detailed review. Finally, 26 papers
      which met the criteria of eligibility were independently selected by the two
      reviewers. The kappa score for agreement on this decision was 0.92. Disagreement
      regarding inclusion of both abstracts and full papers was resolved by discussion
      between the reviewers. No randomized controlled trials (RCT) could be retrieved
      that were specifically designed to answer the question formulated at the outset
      of this systematic review. From the 10 controlled studies, four provide a
      definitive 'yes' that SGD is effective with regard to clinical outcomes. In the
      one study where subgingival debridement was not supported by oral hygiene
      instruction, the paper provided a definitive 'no'. The weighted mean of
      attachment gain of SGD in pockets initially >or=5 mm was 0.64 mm as compared with
      0.37 mm for supragingival plaque control only (SPC). The reduction of pocket
      depth was 0.59 mm and 1.18 mm for SPC and SGD, respectively. Of the 18 papers
      that provided only information on the effect of treatment as compared with the
      baseline values, eight showed SGD to be beneficial with regard to clinical
      attachment level change while the remaining 10 provided no such an analysis. The
      weighted mean of this effect was a 0.74-mm gain of attachment as a result of
      treatment in pockets initially >or= 4 mm. CONCLUSIONS: In patients with chronic
      periodontitis, subgingival debridement (in conjunction with supragingival plaque
      control) is an effective treatment in reducing probing pocket depth and improving
      the clinical attachment level. In fact it is more effective than supragingival
      plaque control alone.

PMID- 12787208
TI  - A systematic review of efficacy of machine-driven and manual subgingival
      debridement in the treatment of chronic periodontitis.
AB  - OBJECTIVES: The purpose of this systematic review was to determine the efficacy
      of machine-driven compared with manual subgingival debridement in the treatment
      of periodontitis. BACKGROUND: Mechanical debridement of the periodontal pocket
      plays a pivotal role in the treatment of periodontitis. METHODS: A literature
      search for controlled clinical trials with at least 6 months' follow-up comparing
      machine-driven instruments with hand instruments for the treatment of chronic
      periodontitis was performed up to April 2001. Screening of titles and abstracts
      as well as data extraction was conducted independently by two reviewers (J.T. &
      T.F.F.). As primary outcome variable, the prevention of tooth loss was used;
      secondary outcome variables were the prevention of disease progression, the
      resolution of anatomical defects and the resolution of gingival inflammation.
      Efficiency was assessed by mean time needed to treat one tooth. RESULTS: From a
      total of 419 abstracts, 27 articles were included for the review. The weighted
      kappa score for agreement between the two reviewers was 0.77, 95% CI: 0.65-0.89,
      indicating substantial agreement. No study reported on the selected primary
      outcome variables. Using clinical attachment gain, probing pocket depth reduction
      or bleeding on probing reduction as outcome variables, there appeared to be no
      differences between ultrasonic/sonic and manual debridement. No major differences
      in the frequency or severity of adverse effects were found. However no meta
      analysis could be performed on any of the previously mentioned parameters.
      Ultrasonic/sonic debridement was found to take significantly less time, i.e.
      36.6%, than debridement using hand instruments (P = 0.0002, 95% CI of the
      standardized effect estimate: 0.39-1.37, heterogeneity P = 0.77). CONCLUSIONS:
      With respect to clinical outcome measures, the available data do not indicate a
      difference between ultrasonic/sonic and manual debridement in the treatment of
      chronic periodontitis for single-rooted teeth; however, the evidence for this is
      not very strong. In addition, ultrasonic/sonic subgingival debridement requires
      less time than hand instrumentation. Further research is needed to assess the
      efficacy of machine-driven debridement on multirooted teeth and clinical outcome
      variables having tangible benefit to the patients should be used.

PMID- 12787209
TI  - A systematic review on the use of residual probing depth, bleeding on probing and
      furcation status following initial periodontal therapy to predict further
      attachment and tooth loss.
AB  - BACKGROUND: Chronic periodontitis affects many adults. Initial cause related
      therapy (ICRT) is aimed at elimination of factors causing disease progression.
      OBJECTIVES: To use a systematic review process of peer reviewed publications to
      assess the predictive value of residual probing depths (PD), bleeding on probing
      (BOP) and furcation involvement (FI) in determining further loss of attachment
      and tooth loss following ICRT. MATERIAL AND METHODS: An electronic search of the
      Cochrane Oral Health Group specialized register, MEDLINE and EMBASE, was
      performed using specific search terms to identify studies assessing the
      predictive value of residual probing depths (PD), bleeding on probing (BOP) and
      furcation involvement (FI) in determining further loss of attachment and tooth
      loss following ICRT. RESULTS: The searches resulted in 941 uniquely identified
      studies. Titles and abstracts were then independently screened by two reviewers
      (S.R. and G.R.P.) to identify publications that met specific inclusion criteria.
      The agreement between the reviewers was assessed and statistical analysis failed
      to demonstrate a difference between the two reviewers (kappa-value: 0.94, P =
      0.003). Detailed review of 47 included publications resulted in acceptance of one
      publication which utilized data based on patient as unit of observation. This
      study included 16 subjects over 42 months demonstrating that residual probing
      depths are predictive of further disease progression whereas persisting bleeding
      on probing are not. CONCLUSIONS: Data based on one study suggest that residual
      probing depths are predictive of further disease progression. The implications
      for carefully designed multicentre randomized clinical control trials are many.

PMID- 12787211
TI  - A systematic review of the effect of surgical debridement vs non-surgical
      debridement for the treatment of chronic periodontitis.
AB  - OBJECTIVE: To systematically review the evidence of effectiveness of surgical vs.
      non-surgical therapy for the treatment of chronic periodontal disease. METHODS: A
      search was conducted for randomized controlled trials of at least 12 months
      duration comparing surgical with non-surgical treatment of chronic periodontal
      disease. Data sources included the National Library of Medicine computerised
      bibliographic database MEDLINE, and the Cochrane Oral Health Group (COHG)
      Specialist Trials Register. Screening, data abstraction and quality assessment
      were conducted independently by multiple reviewers (L.H., F.H., L.T.). The
      primary outcome measures evaluated were gain in clinical attachment level (CAL)
      and reduction in probing pocket depth (PPD). RESULTS: The search provided 589
      abstracts of which six randomized controlled trials were included. Meta-analysis
      evaluation of these studies indicated that 12 months following treatment,
      surgical therapy resulted in 0.6 mm more PPD reduction (WMD 0.58 mm; 95% CI 0.38,
      0.79) and 0.2 mm more CAL gain (WMD 0.19 mm; 95% CI 0.04, 0.35) than non-surgical
      therapy in deep pockets (>6 mm). In 4-6 mm pockets scaling and root planing
      resulted in 0.4 mm more attachment gain (WMD -0.37 mm; 95% CI -0.49, -0.26) and
      0.4 mm less probing depth reduction (WMD 0.35 mm; 95% CI 0.23, 0.47) than
      surgical therapy. In shallow pockets (1-3 mm) non-surgical therapy resulted in
      0.5 mm less attachment loss (WMD -0.51 mm; 95% CI -0.74, -0.29) than surgical
      therapy. CONCLUSIONS: Both scaling and root planing alone and scaling and root
      planing combined with flap procedure are effective methods for the treatment of
      chronic periodontitis in terms of attachment level gain and reduction in gingival
      inflammation. In the treatment of deep pockets open flap debridement results in
      greater PPD reduction and clinical attachment gain.

PMID- 12787212
TI  - A systematic review of guided tissue regeneration for periodontal furcation
      defects. What is the effect of guided tissue regeneration compared with surgical
      debridement in the treatment of furcation defects?
AB  - OBJECTIVES: To systematically review the evidence of effectiveness of guided
      tissue regeneration (GTR) for furcation defects. BACKGROUND: The evidence for the
      effectiveness of GTR in furcation defects has not yet been systematically
      appraised. METHODS: We searched for randomized controlled trials with at least 6
      months' follow-up comparing GTR with surgical debridement (open flap debridement,
      OFD). Data sources included electronic databases, hand-searched journals and
      contact with experts. Screening, data abstraction and quality assessment were
      conducted independently by multiple reviewers. The primary outcome measure was
      reduction in open horizontal furcation depth, secondary outcomes were frequency
      of furcation closure, gain in horizontal and vertical probing attachment and
      reduction of vertical probing depth. RESULTS: For the primary outcome, reduction
      in horizontal furcation depth assessed during re-entry, the weighted mean
      difference between GTR and control was 1.51 mm (95% CI [0.39-2.62], chi-square
      for heterogeneity 67.6 (df = 3), P < 0.001) in mandibular class II furcations,
      1.05 mm (95% CI [0.46-1.64, chi-square for heterogeneity 34.9 (df = 3), P <
      0.001) in maxillary class II furcations, and 0.87 mm (95% CI [-0.08-1.82], chi
      square for heterogeneity 0.1 (df = 4), P = 0.991) in studies that had combined
      mandibular and maxillary class II furcations. For the secondary outcomes, GTR
      treatment led to significantly better results than open flap debridement. No meta
      analysis could be performed for frequency of furcation closure because of sparse
      data. CONCLUSIONS: Overall, GTR was consistently more effective than OFD in
      reducing open horizontal furcation depths, horizontal and vertical attachment
      levels and pocket depths for mandibular or maxillary class II furcation defects.
      However, these improvements were modest, variable and there was only a limited
      number of studies available to appraise the effects, thus limiting general
      conclusions about the clinical benefit of GTR. Future studies should aim to
      identify factors associated with achieving consistent and more pronounced
      benefits over open flap debridement.

PMID- 12787213
TI  - A systematic review of graft materials and biological agents for periodontal
      intraosseous defects.
AB  - OBJECTIVES: To determine the adjunctive effect of grafting
      biomaterials/biological agents with open flap debridement (OFD) in the treatment
      of deep intraosseous defects. BACKGROUND: No systematic review of treatment
      outcomes in patients who received graft biomaterials or biological agents have
      been published. METHODS: A rigorous systematic review of randomized controlled
      trials of at least 6-month duration was conducted comparing grafting
      biomaterials/biological agents (alone or in combination) + OFD (test group) to
      OFD alone or in combination with a placebo (control group). RESULTS: The
      difference in CAL change between test and control groups varied from -1.45 mm to
      1.40 mm with respect to different biomaterials/biological agents. Meta-analysis
      showed that CAL change significantly improved after treatment for coralline
      calcium carbonate (weighted mean difference 0.90 mm; 95% CI: 0.53-1.27),
      bioactive glass (weighted mean difference 1.04 mm; 95% CI: 0.31-1.76),
      hydroxyapatite (weighted mean difference 1.40 mm, 95% CI 0.64-2.16), and enamel
      matrix proteins (weighted mean difference 1.33 mm, 95% CI 0.78-1.88). However,
      heterogeneity in results between studies was highly statistically significant for
      most of biomaterials/biologicals and could not be fully explained. CONCLUSIONS:
      Overall, the use of specific biomaterials/biologicals was more effective than OFD
      in improving attachment levels in intraosseous defects. Difference in CAL gain
      varied greatly with respect to different biomaterial/biological agent. Due to a
      significant heterogeneity in results between studies in most treatment groups,
      general conclusions about the expected clinical benefit of graft
      biomaterials/biologicals need to be interpreted with caution. Further research
      should focus on understanding this variability.

PMID- 12787214
TI  - A systematic review on the effect of systemic antimicrobials as an adjunct to
      scaling and root planing in periodontitis patients.
AB  - BACKGROUND: Scaling and root planing (SRP) are the bases of non-surgical therapy
      in the treatment of periodontitis. However, results from this therapy are often
      unpredictable and dependable from many different factors. OBJECTIVES: The aim of
      this systematic review was to evaluate the effectiveness of the adjunctive use of
      systemic antimicrobials with scaling and root planing (SRP) vs. SRP alone in the
      treatment of chronic (CP) or aggressive periodontitis (AgP). SEARCH STRATEGY: Use
      of computerized databases, namely MEDLINE, the Cochrane Oral Health Group
      Specialty Trials Register and EMBASE; reference lists from relevant articles were
      hand-searched; and a hand-search of selected journals until April 2001. SELECTION
      CRITERIA: Studies were selected if they were designed as controlled clinical
      trials in which systemically healthy patients with either AgP or CP were treated
      with SRP plus systemic antimicrobials in comparison with SRP alone or with
      placebo, for a minimum of 6 months. Main outcome measures were clinical
      attachment level (CAL) change and probing pocket depth (PPD) change. DATA
      COLLECTION AND ANALYSIS: Two reviewers extracted independently information
      regarding quality and study characteristics, in duplicate. Kappa scores
      determined their agreement. Main results were collected and grouped by drug,
      disease and PPD category. For the quantitative data synthesis, the data was
      pooled (when mean differences and standard errors were available), and either a
      Fixed Effects or Random Effects meta-analysis was used for the analysis. RESULTS:
      After an initial selection, 158 papers were identified by the manual and
      electronic searches; 25 papers were eligible for inclusion. Their quality
      assessment showed that randomization and allocation concealment methods were
      seldom reported and blindness was usually not defined clearly. In general,
      selected studies showed high variability and lack of relevant information for an
      adequate assessment. Overall, SRP plus systemic antimicrobial groups demonstrated
      better results in CAL and PPD change than SRP alone or with placebo groups. Only
      limited meta-analyses could be performed, due to the difficulties in pooling the
      studies and the lack of appropriate data. This analysis showed a statistically
      significant additional benefit for spiramycin (PPD change) and
      amoxicillin/metronidazole (CAL change) in deep pockets. CONCLUSION: Systemic
      antimicrobials in conjunction with SRP, can offer an additional benefit over SRP
      alone in the treatment of periodontitis, in terms of CAL and PPD change, and
      reduced risk of additional CAL loss. However, differences in study methodology
      and lack of data precluded an adequate and complete pooling of data for a more
      comprehensive analyses. It was difficult to establish definitive conclusions,
      although patients with deep pockets, progressive or 'active' disease, or specific
      microbiological profile, can benefit more from this adjunctive therapy.

PMID- 12787216
TI  - Supportive periodontal care: the effect of periodic subgingival debridement
      compared with supragingival prophylaxis with respect to clinical outcomes.
AB  - BACKGROUND: The programme of supportive periodontal care (SPC) is essential to
      the long-term stability of patients with chronic periodontitis. The clinical
      strategy for SPC is often determined according to 'clinical needs' of the patient
      and is thus determined by clinical observation and individual decision-making
      rather than being based on the best available clinical evidence. OBJECTIVE: To
      evaluate the effectiveness of supragingival prophylaxis vs. sub-gingival
      debridement for SPC following the treatment of chronic periodontitis. SEARCH
      STRATEGY: Computerized for Medline and the Cochrane Oral Health Group Specialty
      Trials Register. Hand searching of the Journals of Clinical Periodontology,
      Periodontal Research and Periodontology. Reference lists from relevant articles
      were scanned and the authors of eligible studies were contacted to obtain
      additional information. SELECTION CRITERIA: Studies were selected if they were
      designed as a prospective clinical trial in which patients with chronic
      periodontitis had followed a programme of SPC, which included at least one of the
      regimens of interest in part of the mouth, for a minimum of 12 months. DATA
      COLLECTION AND ANALYSIS: Information regarding methods, patients, interventions
      (SPC), outcome measures and results were extracted independently, in duplicate,
      by two reviewers (P.A.H., G.McC.). Absent data were recorded as such and
      incomplete data were sought from the researchers wherever possible. RESULTS: In
      all, 28 papers were identified by the manual and electronic searches; 11 papers
      were eligible for inclusion. Only one study reported a direct comparison of the
      two SPCs of interest. The data were reported as mean changes in probing depth and
      attachment level between baseline and the 12-month follow-up point. For coronal
      scaling DeltaPD = 0.59 mm [0.13], DeltaAL = -0.13 mm [0.19]. For subgingival
      debridement DeltaPD = 0.37 mm [0.15], DeltaAL = -0.14 mm [0.18]. There were no
      significant differences between the SPC regimens. The weighted mean DeltaPD [95%
      confidence intervals] for the five additional studies that reported supragingival
      prophylaxis as the SPC regimen was 1.15 mm [-0.17, 2.38]. The weighted mean
      DeltaPD [95% confidence intervals] for the four studies that reported subgingival
      debridement as the SPC regimen was 0.56 mm [0.37, 1.47]. The difference between
      the SPC treatments for the mean DeltaPD is therefore 0.23 mm. The confidence
      interval for the combined studies was very wide [0.37, 1.47] and very little
      additional information is gained unless some strong assumptions are made about
      the comparability of the populations from which the samples are drawn. Such an
      assumption was not considered appropriate. The weighted mean DeltaAL [95%
      confidence intervals] for the six additional studies that reported supragingival
      prophylaxis as the SPC regimen was 0.18 mm [-0.38, 0.74]. The weighted mean
      DeltaAL [95% confidence intervals] for the six additional studies that reported
      supragingival prophylaxis as the SPC regimen was 0.50 mm [0.11, 0.89]. The
      difference between the SPC treatments for mean DeltaAL is 0.32 mm. The confidence
      interval [-0.36, 1.00] is very wide and the data from the additional studies
      provide little extra information than that reported in the one study that
      compared the treatments directly. CONCLUSION: It is not possible to make any firm
      recommendations regarding clinical practice based on the crude meta-analysis and
      the review of these 11 studies. The best available evidence indicates that SPC
      regimens of supragingival prophylaxis and subgingival debridement are comparable
      with respect to the clinical outcomes of probing depth and attachment levels at
      12 months post non-surgical treatment.

PMID- 12787217
TI  - A systematic review of the prevalence of root sensitivity following periodontal
      therapy.
AB  - OBJECTIVES: To systematically review the evidence on the prevalence of root
      sensitivity following periodontal therapy. MATERIAL AND METHODS: Cross-sectional
      and longitudinal clinical studies were searched for in electronic databases, hand
      searched journals and through contact with authors directly. The screening and
      data extraction were conducted by several reviewers independently. The main
      outcome measure was prevalence of root sensitivity following periodontal therapy.
      RESULTS: The prevalence of root sensitivity was 9-23% before and 54-55% after
      periodontal therapy. An increase in the intensity of root sensitivity occurred 1
      3 weeks following therapy, after which it decreased. CONCLUSIONS: It is concluded
      that there are insufficient randomized controlled trials to adequately address
      the stipulated question. However, based on the scarce evidence from only two
      studies, root sensitivity occurs in approximately half of the patients following
      subgingival scaling and root planing. The intensity of root sensitivity increases
      for a few weeks after therapy, after which it decreases. In clinical practice, it
      may be recommended that patients should be made aware of the potential for root
      sensitivity prior to treatment. In research, it may be recommended to conduct
      randomized controlled and prospective studies with both short and long follow-up
      periods. Furthermore, to investigate the effects and the relationship of root
      instrumentation with the aetiology of root sensitivity, the efficacy of
      preventive and therapeutic regimes for root sensitivity, and the incidence and
      severity of root sensitivity by subjective patient-reporting, and the response to
      different modes of stimuli. Protocols should follow the criteria used in dentine
      hypersensitivity studies.

PMID- 12787218
TI  - Periodontal plastic surgery for treatment of localized gingival recessions: a
      systematic review.
AB  - BACKGROUND: The evidence for the efficacy of periodontal plastic surgery (PPS) in
      the treatment of recession defects has not yet been systematically evaluated. The
      objective of this review was to systematically review the efficacy of PPS in
      achieving root coverage in the treatment of localized gingival recession. The
      following surgical procedures have been considered in this review: guided tissue
      regeneration (GTR), free gingival graft (FGG), connective tissue graft (CTG), and
      coronally advanced flap (CAF). METHODS: Randomized and controlled trials, as well
      as case series of at least 6 months' follow-up, were searched. Data sources
      included electronic databases and hand-searched journals. Screening, data
      abstraction and quality assessment were conducted independently and in duplicate.
      RESULTS: Regarding recession reduction, a limited but statistically significant
      greater benefit was found for CTG compared with GTR (weighted mean difference:
      0.43 mm, 95% CI: 0.62-0.23). No differences were found comparing either GTR with
      CAF or resorbable versus non-resorbable GTR barriers. Gain in attachment was also
      similar for each of the three comparisons. Analysis of single arms of trials and
      case series demonstrated that PPS can have a marked improvement on clinical
      parameters but heterogeneity was often high and only partly explained by initial
      defect depth. CONCLUSIONS: Overall, PPS was effective in reducing gingival
      recessions with a concomitant improvement in attachment levels. Even though no
      single treatment can be considered superior to all the others, CTG was
      statistically significantly more effective than GTR in recession reduction.
      Further research is needed to identify the factors most associated with
      successful outcomes.

PMID- 12787220
TI  - A systematic review of the incidence of biological and technical complications in
      implant dentistry reported in prospective longitudinal studies of at least 5
      years.
AB  - OBJECTIVE: To systematically review the incidence of biological and technical
      complications in implant therapy reported in prospective longitudinal studies of
      at least 5 years. METHODS: A MEDLINE search was conducted for prospective
      longitudinal studies with follow-up periods of at least 5 years. Screening and
      data abstraction were performed independently by multiple reviewers. The types of
      complications assessed were as follows: implant loss, sensory disturbance, soft
      tissue complications, peri-implantitis, bone loss >or=2.5 mm, implant fracture
      and technical complications related to implant components and suprastructures.
      RESULTS: The search provided 1310 titles and abstracts, out of which 159 were
      selected for full-text analysis. Finally, 51 studies were included. Meta analysis
      of these studies indicated that implant loss prior to functional loading is to be
      expected to occur in about 2.5% of all implants placed in implant therapy
      including more than one implant and when routine procedures are used. Implant
      loss during function occurs in about 2-3% of implants supporting fixed
      reconstructions, while in overdenture therapy >5% of the implants can be expected
      to be lost during a 5-year period. Few studies (41% of those included) reported
      data on the incidence of persisting sensory disturbance >1 year following implant
      surgery. Most of the studies that provided such data reported on the absence or a
      low incidence (1-2%) of this complication beyond this interval. A higher
      incidence of soft tissue complications was reported for patients treated with
      implants supporting overdentures. There is limited information regarding the
      occurrence of peri-implantitis and implants exhibiting bone loss >or=2.5 mm.
      Implant fracture is a rare complication and occurs in <1% of all implants during
      a 5-year period. The incidence of technical complications related to implant
      components and suprastructures was higher in overdentures than in fixed
      reconstructions. CONCLUSION: Implant loss was most frequently described (reported
      in about 100% of studies), while biological complications were considered in only
      40-60% and technical complications in only 60-80% of the studies. This
      observation indicates that data on the incidence of biological and technical
      complications may be underestimated and should be interpreted with caution.

PMID- 12787221
TI  - A systematic review of the effect of anti-infective therapy in the treatment of
      peri-implantitis.
AB  - The aim of this systematic review was to assess the treatment of peri-implantitis
      with special emphasis on the role of anti-infective therapy. No randomized
      controlled clinical trial was available for analysis. Of 145 peri-implant studies
      initially screened, 21 studies (six human and 15 animal studies) were analysed
      regarding the outcome of treatment of peri-implantitis. A multitude of treatment
      regimens, including anti-infective therapy, was reported. The antibiotic regimens
      varied between studies. No standardized medication protocol was used. Type of
      antibiotic, dosage, duration and time for initiation of antibiotic treatment were
      different for all studies, but details were not always reported. A non-medicated
      control group was reported in one animal experiment only. The outcomes following
      anti-infective treatment of peri-implantitis are highly variable. The evidence
      for a consistent and clinically relevant advantage using antibiotics can be
      questioned in this context. There are to date no data available to support
      specific treatment protocols. It is suggested that randomized human controlled
      clinical trials for the treatment of peri-implantitis be initiated.

PMID- 12787222
TI  - A systematic review of the survival of implants in bone sites augmented with
      barrier membranes (guided bone regeneration) in partially edentulous patients.
AB  - The aim of the present systematic review was to assess the survival of implants
      in regenerated bone applying the method of guided bone regeneration (GBR)
      compared with the survival of implants in non-regenerated bone. Studies to be
      included in this review needed to provide at least 12-month results following
      prosthetic reconstruction of titanium implants in bone regenerated by GBR with or
      without membrane supporting materials. The outcome measures were implant survival
      described as presence of implant, implant success (according to the criteria in
      the respective study), absence of clinical implant mobility, absence of implant
      fracture, absence of progressive peri-implant crestal bone loss as assessed on
      radiographs without clinical signs of peri-implant infection, absence of peri
      implant infection with suppuration. A MEDLINE search and a hand search of
      relevant scientific journals were conducted including studies from the year 1990
      to May 2001. A total of 11 studies could be identified fulfilling the inclusion
      criteria. All studies except two had the characteristics of case series or cross
      sectional surveys. The two different studies had both test and control implants
      included in their analysis and qualified as controlled clinical trials.
      Cumulative success or survival rates, respectively, for implants in regenerated
      bone ranged from 100% after 5 years to 79.4% after 5 years of function. Regarding
      survival data, no significant differences were found in the controlled clinical
      trials between implants in regenerated compared to implants in non-regenerated
      bone. Within the limits of this systematic review characterized by second and
      third levels of evidence, the following conclusions can be drawn: The survival
      rate of implants placed into sites with regenerated/augmented bone using barrier
      membranes varied between 79% and 100% with the majority of studies indicating
      more than 90% after at least one year of function. The survival rates obtained in
      the present systematic review are similar to those generally reported for
      implants placed conventionally into sites without the need for bone augmentation.

PMID- 12787228
TI  - Constructions of spirituality in contemporary nursing theory.
AB  - BACKGROUND: The nursing literature on spirituality tends to agree that modern
      science is relatively powerless to address the loss of personal meaning
      experienced by people facing death, suffering and loss. As a remedy, the
      literature recommends addressing patients' spirituality. The typical analytical
      move is to distinguish spirituality from religion and consider it a part,
      dimension or property of the patient. AIM AND METHOD: This paper uses discourse
      analysis to identify the formal properties of scientific and religious discourses
      and their social and political implications. The nursing literature is then
      investigated to detect the use of such discourses in constructing the object
      spirituality and to consider any implications for nursing as a social practice.
      FINDINGS: Far from escaping science and religion, the literature constructs
      spirituality by means of scientific and religious discourses. These discourses
      have characteristic strengths and weaknesses that the nursing literature seems to
      miss. Accordingly, its use of religious discourse lacks coherence and depth, and
      risks merging human with transcendent authority. Its use of scientific discourse
      lacks precision and clarity and risks intensifying those features of modernity
      which contribute to a loss of personal meaning in the face of death, suffering
      and loss. CONCLUSION: Nursing literature on spirituality raises important
      questions but is limited in its capacity to address them. This paper provides an
      alternative perspective. First, it draws on an analysis of the modern
      institutional environment and its existential dimension. Secondly, it applies
      discourse analysis to the task of helping people experiencing illness and injury.
      This approach respects the strengths and limitations of both scientific and
      religious discourses.

PMID- 12787229
TI  - Psychometric evaluation of the Spiritual Coping Strategies scale in English,
      Maltese, back-translation and bilingual versions.
AB  - BACKGROUND: The little research that has been done on the topic considers
      spiritual coping as consisting mainly of religious coping strategies. This limits
      spiritual coping solely to believers. However, it is argued that spiritual coping
      should address both believers and non-believers. The development of the new
      Spiritual Coping Strategies (SCS) scale, which consists of both religious and non
      religious coping strategies attempts to fill this research gap. Aim. The aim of
      this article is to discuss the psychometric assessment of the SCS scale designed
      in four versions, namely English, Maltese, back-translation and bilingual.
      METHODS: The Likert-type SCS scale comprises 20 items, each represented by the
      frequency and helpfulness of both religious and non-religious coping strategies.
      Test-retest of the four versions was conducted between October 1999 and January
      2000, with 55 final year nursing students, mean age of 24.5 years, recruited from
      the same class to facilitate supervision and prevent contamination of results.
      Test-retest reliability of the scale was investigated by cross-tabulations, Kappa
      (kappa) measures and Spearman's correlation coefficient. Internal consistency was
      tested by Cronbach's alpha. The correlation structure was examined by the
      multivariate techniques of R-type cluster analysis and direct oblimin factor
      analysis. RESULTS: Cross-tabulations between tests and retests gave highly
      significant values of chi-squared (P < or = 0.0001) for most items in all
      versions of the scale. These cross-tabulations also yielded reasonably good
      values for kappa. Additionally, satisfactory values for Spearman's coefficient of
      correlation resulted between tests and retests. Twelve frequency variables and 13
      helpfulness variables had test-retest correlations in the range 0.5 < or = rs <
      or = 0.79 in at least three of the versions. Optimum values of Cronbach's alpha
      were observed for the helpfulness variable in retests namely, 0.81 for the
      English version, 0.73 for the Maltese version, 0.79 for the back-translation, and
      0.82 for the bilingual version. These values were all above the acceptable
      minimum value of 0.7. The correlation structure identified two factors, namely
      religious and non-religious coping strategies. Although the two factors together
      explained only between 33% and 40% of the variance in the different versions, the
      religious factor had good reliability, with 0.77 < or = alpha < or = 0.82 for the
      four versions, whilst the non-religious factor also had alpha > or = 0.71 for all
      versions except the Maltese one, for which alpha = 0.59. CONCLUSION: Therefore,
      psychometric assessment suggests that the SCS scale, in any of the four versions,
      is a reliable tool which can be used in future studies on SCS in Maltese
      patients.

PMID- 12787230
TI  - Symptom status and health-related quality of life: clinical relevance.
AB  - BACKGROUND: Nursing continues to struggle to identify outcomes that measure
      quality of care. Health-related quality of life (HRQOL) has been identified as an
      outcome indicator that is sensitive to health-care interventions. However,
      clinicians remain skeptical about its relevance. AIM: This article discusses the
      conceptual issues surrounding HRQOL research and provides an example that
      demonstrates how symptom status can serve as a clinically relevant and measurable
      dimension of HRQOL. METHODS: The study sample (n = 99) were patients presenting
      to the emergency department of an academic medical centre in the United States of
      America (USA) between July 1997 and March 1999 with the diagnosis of
      gastrointestinal bleeding. The mean age was 57.86 (17.52) years and 62.6% of the
      sample was male. The Short Form-12 (SF-12) (measurement used for HRQOL) and a 15
      item symptom checklist were administered within the first 24 hours following the
      emergency department visit and by phone 1 month after discharge. RESULTS:
      Regression analysis controlling for age, gender, haematocrit and comorbidities
      was used to examine the relationships between symptom status and HRQOL. The
      analysis suggests that symptom status is a key predictor of HRQOL. STUDY
      LIMITATIONS: The sample was a relatively small convenience sample from one
      emergency department in the USA. CONCLUSIONS: Nurses are concerned with improving
      patients' HRQOL. Certainly, symptoms are amenable to nursing interventions. We
      provide one example that demonstrates the relationship between symptom status and
      HRQOL. By tracking and studying trends in the number of symptoms over time we can
      begin to track HRQOL as an outcome of care. Thus, we conclude that by helping
      patients manage their symptoms their overall HRQOL would improve.

PMID- 12787231
TI  - Mothers' involvement in caring for their premature infants: an historical
      overview.
AB  - BACKGROUND: Advances in technology have resulted in increasing survival rates
      even for extremely premature infants. While sophisticated medical management is
      vital to infant survival, research has found that social factors and care giving
      processes are important predictors of infants' later outcome. Consequently,
      evidence is accumulating to demonstrate the fundamental role of mothers and
      families to the optimal developmental outcome of premature infants. AIM: The aim
      of the work reported here was to undertake an historical overview of premature
      infant care practices to increase neonatal nurse's knowledge of the crucial role
      of mothers and families in the care of their premature infants. Understanding
      past practice and current trends can provide neonatal nurses with critical
      insight which will assist in formulating current and future care. METHOD:
      Research and historical articles focusing on maternal involvement in preterm
      infant care from the development of the incubator to the present time were
      examined. A search of the literature between 1960 and 2002 was conducted using
      the MEDLINE, CINAHL and PSYCLIT databases. The search terms were premature
      infant, neonatal intensive care, history, and maternal care. FINDINGS: Three
      major themes were identified which reflect the development of neonatal care.
      Firstly, over the last century advances in medical and public health practice saw
      a decline in mortality rates for mothers and infants. Secondly, the application
      of this new knowledge resulted in the institutionalization and
      professionalization of obstetric and neonatal care which, in turn, resulted in
      the isolation of infants from their mothers. Finally, concurrent advances in
      infant research emphasized the importance of mother-infant relationships to
      infants' developmental outcome, resulting in greater flexibility in hospital
      practices regarding parental contact with their infants. CONCLUSION: As
      biomedical advances in technology continue to help smaller, sicker premature
      infants to survive, neonatal nurses are strategically placed to promote positive
      outcomes for infants and their families through the integration of social science
      and behavioural research into nursing practice.

PMID- 12787232
TI  - Pain management in nursing procedures on premature babies.
AB  - BACKGROUND: Pain can be caused to premature babies when nursing and other
      procedures are carried out. Procedural pain management for these babies raises
      challenging questions for health care professionals. Optimal pain management for
      premature babies can be reached by using and further developing existing
      pharmacological and non-pharmacological pain alleviation methods for procedural
      pain before, during, and after procedures. AIMS: The aims of this study were to
      describe the environment of pain management in nursing procedures and
      examinations with premature babies; to describe preparation of the baby for the
      procedure; to describe non-pharmacological pain alleviation methods during and
      after the procedures; and to develop a process describing procedural pain
      management in premature babies. METHOD: The material for this study consisted of
      journal articles on non-pharmacological procedural pain alleviation in infants
      published between 1994 and 2002. During this period knowledge of pain management
      in premature babies has improved considerably. The study was based on the method
      of content analysis. FINDINGS: Procedural pain management in premature babies was
      described by researchers as a process comprising: (1) an environment that is
      favourable to effective pain management, (2) safe preparation of the baby for the
      procedure, (3) pain alleviation during the procedure, and (4) restoring the
      baby's sense of security after the procedure. Pain management is recommended to
      be used alone or together with pharmacological interventions. Additionally,
      systematic pain management requires documentation of the whole pain management
      process. CONCLUSION: Pain management can be described as a process. It is
      important to test and assess this process and individual non-pharmacological pain
      management methods in practical nursing situations. The findings of this review
      can be used to improve pain management methods in premature babies.

PMID- 12787233
TI  - Life with a rare chronic disease: the scleroderma experience.
AB  - BACKGROUND: Little is known about the experience of living with a rare disease
      and how people with rare diseases cope with not only the disease but also the
      reactions of others. Scleroderma is a rare chronic connective tissue disease that
      results in fibrotic changes involving all or some organs of the body. The two
      types of scleroderma are systemic scleroderma, which involves the skin and
      internal organs and is the more serious type, and local scleroderma, which
      attacks the skin and surrounding tissues. Some people with scleroderma have signs
      that are visible to outsiders, while others have invisible signs. Having this
      chronic condition and being different from the general population may subject
      people with scleroderma to stigmatization by others. AIM: The aim of this study
      was to understand, from the individual's perspective, the experience of living
      with scleroderma. METHOD: Focus group interviews were conducted with two groups
      of individuals with scleroderma. Because of the rarity of the disease and the
      illness of the participants, only two groups were held. The same questions were
      asked of both groups. A moderator and assistant guided the groups. FINDINGS: Data
      analysis revealed five themes: physical manifestations, disclosure/non-disclosure
      to others, living, being normal and facing the future. The data are discussed in
      light of participants' having visible signs, invisible signs and the rarity of
      their condition. For those with visible signs, disclosure was automatic. They
      were conscious of being different from others without scleroderma. Those with
      invisible signs managed their disease information in such a way as to minimize
      the stigma of being different. The rarity of the disease added the problem of
      others not understanding their difficulties. Those who disclosed their disease
      not only had to deal with the reactions of others, but faced the additional
      burden of having to explain their condition. CONCLUSION: Nurses may have little
      knowledge about scleroderma. It is possible that they, through their ignorance of
      such rare conditions, may stigmatize individuals. Through understanding about
      rare diseases will they be able to teach patients the skills necessary to help
      them cope with their symptoms, as well as the reactions of others to their
      diagnosis and appearance.

PMID- 12787234
TI  - The impact of incontinence on older spousal caregivers.
AB  - BACKGROUND: The role of informal spousal caregivers has increased as the
      population ages, levels of disability in society increase, and governments seek
      to restrain expenditure on the provision of institutional health care. Care
      giving has attracted a vast body of research, largely directed at caregiver
      burden. Incontinence, however, has been relatively unexplored, despite being a
      common problem faced by caregivers, and being recognised as a major caregiver
      burden and predictor of institutional placement. AIMS: This study began to
      explore the impact of care recipient incontinence on major care providers, that
      is, their spouses. APPROACH: A qualitative approach based on the grounded theory
      method was used. Eight home-based caregivers of spouses with incontinence were
      interviewed. FINDINGS: Data analysis revealed a number of categories, grouped
      under three major themes: underpinnings, processes and consequences. The
      underpinnings were lifelong love and friendship, and acceptance; the processes
      were problem-solving and constant watchfulness. The consequences were role
      change, financial cost, decreased intimacy, emotional responses, sleeping issues
      and social isolation. DISCUSSION: The research highlighted the interconnectedness
      of factors in the experiences of carers, reinforcing the need for holistic
      assessment beyond a focus on the "continence issue" alone. Nevertheless, simple
      interventions could make substantial differences. A framework is proposed which
      may guide nursing assessment.

PMID- 12787235
TI  - Changing Childbirth: a pilot project.
AB  - OBJECTIVE: To compare the outcomes of an adapted pilot Changing Childbirth
      initiative providing continuity of care by a group of known midwives with
      traditional maternity care. DESIGN: Between-groups trial to compare levels of
      satisfaction and clinical outcomes for two groups of women, cared for either
      under this Changing Childbirth scheme or the traditional model of care. METHOD:
      Of the 200 women who agreed to participate in the project, 100 were randomly
      allocated to the pilot scheme and 100 to the traditional care package. During the
      postpartum period, information was collected via a questionnaire about
      participants' levels of satisfaction with a variety of aspects of care provided
      during the antenatal, delivery and postpartum periods. Data about clinical
      outcomes for the two groups were also obtained. RESULTS: Women in the pilot group
      had significantly more continuity of care throughout each of the three periods,
      were generally more satisfied with their care, felt that they had more choice
      over a variety of aspects of care and experienced no compromise in clinical
      outcomes (P = 0.05 or less in each case). IMPLICATIONS FOR PRACTICE: Many
      previous attempts to introduce the Changing Childbirth initiative have revealed
      significant problems, particularly with regard to the continuity of carer
      requirement. Taking account of local health care needs and existing provision,
      the present study adapted this concept to continuity of care. This did not
      apparently affect any of the guiding principles contained in the original
      document, and yet enhanced satisfaction. It would appear that the Changing
      Childbirth agenda can be adapted and integrated with local health care situations
      without sacrificing any of the overarching principles.

PMID- 12787236
TI  - Identifying cancer nursing research priorities using the Delphi technique.
AB  - BACKGROUND: Nursing research is an integral component of improving the care of
      people with cancer. However, for research to be successfully integrated and
      applied to practice, ownership and identification must come from those in
      practice. The need for local and national strategies for cancer nursing research
      and the importance of establishing priorities for cancer nursing research have
      been repeatedly acknowledged. STUDY AIM: The aim of the study was to facilitate a
      strategic approach to cancer nursing research by identifying the research
      priorities of cancer nurses. RESEARCH METHOD: A three-round Delphi survey was
      administered to nurses (n = 112) attending a cancer nursing research conference
      in Northern Ireland. Participants were asked to identify five research questions
      that they considered a high priority for cancer nursing. A response rate of 54%
      (60 delegates) was obtained for round one and this generated 117 statements.
      These statements were content analysed. Two subsequent quantitative rounds
      followed this. RESULTS: The top priority areas identified were psychosocial
      issues, for example communication and information needs; professional issues
      relating to nurse burnout, stress and nurse-led care; and context of care issues
      including continuity of care. LIMITATIONS: A potential limitation of the study is
      the use of conference delegates. However, it is argued that these are the people
      we wanted to target as they could be considered as experts who already had an
      interest and clinical background in both cancer research and practice.
      CONCLUSION: These priorities have helped to provide both direction and focus for
      the development of a cancer nursing research strategy for Northern Ireland. It is
      recommended that future research questions should be focused around the highest
      ranked priorities.

PMID- 12787237
TI  - Sexual harassment of nurses and nursing students.
AB  - BACKGROUND: Nursing has dealt with sexual harassment long before the term was
      coined during the 1970s. The current study investigated sexual harassment of
      nurses and nursing students in Israel following new legislation against sexual
      harassment in the workplace. METHODS: A self-report questionnaire was
      administered to 281 nurses and 206 nursing students (80% women) from five medical
      centres in Israel. Seven types of sexual harassment behaviour patterns were
      evaluated. FINDINGS: Frequency of sexual harassment decreased as the behaviour
      became more intimate and offensive. Ninety percent of subjects reported
      experiencing at least one type of sexual harassment and 30% described at least
      four types. A significant difference was found between nurses and nursing
      students. Furthermore, "severe" types of behaviour were experienced by 33% of
      nurses, in comparison with 23% of nursing students. Women were significantly more
      exposed than men to "mild" and "moderate" types of sexual harassment, while 35%
      of men vs. 26% of women were exposed to "severe" types of harassment. However,
      women responded significantly more assertively than men to "severe" sexual
      harassment. CONCLUSIONS: Particular attention is needed when sexual harassment
      occurs to male students and nurses because they may be subjected to the more
      offensive sexual conducts and at the same time may lack the ability to respond
      assertively.

PMID- 12787239
TI  - Characterization of Arabidopsis thaliana methyl-CpG-binding domain (MBD)
      proteins.
AB  - Cytosine methylation at symmetrical CpG and CpNpG sequences plays a key role in
      the epigenetic control of plant growth and development; yet, the way by which the
      methylation signal is interpreted into a functional state has not been
      elucidated. In animals, the methylation signal is recognized by methyl-CpG
      binding domain (MBD) proteins that specifically bind methylated CpG
      dinucleotides. In Arabidopsis thaliana, 12 putative MBD proteins were identified
      and classified into seven subclasses. Here, we characterized six MBD proteins
      representing four subclasses (II, III, IV, and VI) of the Arabidopsis MBD family.
      We found that AtMBD7 (subclass VI), a unique protein containing a double MBD
      motif, as well as AtMBD5 and AtMBD6 (subclass IV), bind specifically
      symmetrically methylated CpG sites. The MBD motif derived from AtMBD6, but not
      from AtMBD2, was sufficient for binding methylated CpG dinucleotides. AtMBD6
      precipitated histone deacetylase (HDAC) activity from the leaf nuclear extract.
      The examined AtMBD proteins neither bound methylated CpNpG sequences nor did they
      display DNA demethylase activity. Our results suggest that AtMBD5, AtMBD6, and
      AtMBD7 are likely to function in Arabidopsis plants as mediators of the CpG
      methylation, linking DNA methylation-induced gene silencing with histone
      deacetylation.

PMID- 12787240
TI  - The intermembrane space of plant mitochondria contains a DNase activity that may
      be involved in programmed cell death.
AB  - The key role for mitochondria in mammalian apoptosis, a form of programmed cell
      death (PCD), is well established, but a similar role for plant mitochondria is
      just emerging. In order to unravel the molecular mechanisms linking plant
      mitochondria to the downstream events of PCD, we have developed an Arabidopsis
      cell-free system that can be used to monitor biochemical and morphological
      changes in isolated nuclei that are associated with PCD. Using this system, two
      activities that resulted in nuclear DNA degradation could be distinguished, both
      of which were facilitated by the addition of mitochondria. One activity mediated
      the generation of 30 kb DNA fragments within 3 h and chromatin condensation
      within 6 h, when nuclei were incubated with mitochondria alone. The second
      activity required cytosolic extract in addition to mitochondria and resulted in
      oligonucleosome-sized DNA cleavage after >12 h. Submitochondrial fractionation
      and pharmacological studies suggested the presence of an Mg2+-dependent nuclease
      activity in the intermembrane space, which is responsible for the former in vitro
      activity. The evolutionary conservation of the role of mitochondria in PCD in
      animals and plants is discussed.

PMID- 12787241
TI  - Leucine-rich repeat-mediated intramolecular interactions in nematode recognition
      and cell death signaling by the tomato resistance protein Mi.
AB  - The root-knot nematode resistance gene Mi from tomato encodes a nucleotide
      binding/leucine-rich repeat (NB/LRR) protein with a novel amino-terminal domain
      compared to related disease-resistance genes. The closely linked paralog Mi-1.1,
      which does not confer nematode resistance, encodes a protein 91% identical to the
      functional copy, Mi-1.2. The chimeric construct Mi-DS3, which encodes the 161
      amino-terminal residues from Mi-1.1 fused to the remainder of Mi-1.2, induces
      localized necrosis when transiently expressed in Nicotiana benthamiana leaves. We
      produced mutant constructs that exchanged sequences encoding each of the 40 amino
      acid differences from the Mi-1.1 LRR region into Mi-DS3 and into Mi-1.2. For 23
      of the substitutions, necrosis was lost upon transient expression of the mutated
      Mi-DS3 in N. benthamiana, and nematode resistance was lost when the altered Mi
      1.2 was expressed in the tomato roots. One substitution, R961D, failed to give Mi
      DS3-induced necrosis, but produced a dominant lethal phenotype when introduced
      into Mi-1.2. This gain-of-function phenotype was suppressed by co-expression with
      the amino-terminal region of Mi-1.1, suggesting that residue 961 is critical for
      negative regulation by the corresponding N-terminal region. Substitutions of Mi
      1.1 residues 984-986 retained the ability to cause necrosis in Mi-DS3, but
      resulted in loss-of-nematode resistance in Mi-1.2, suggesting that these residues
      are essential for nematode recognition. None of the loss-of-function mutations in
      Mi-1.2 had a dominant negative phenotype. These results indicate that the Mi-1.2
      LRR is involved in regulation of the transmission of the resistance response as
      well as in recognition of the nematode.

PMID- 12787242
TI  - Substrate preference of stress-activated phospholipase D in Chlamydomonas and its
      contribution to PA formation.
AB  - In response to various environmental stress conditions, plants rapidly form the
      intracellular lipid second messenger phosphatidic acid (PA). It can be generated
      by two independent signalling pathways via phospholipase D (PLD) and via
      phospholipase C (PLC) in combination with diacylglycerol kinase (DGK). In the
      green alga Chlamydomonas, the phospholipid substrates for these pathways are
      characterized by specific fatty acid compositions. This allowed us to establish:
      (i) PLD's in vivo substrate preference; and (ii) PLD's contribution to PA
      formation during stress signalling. Accordingly, G-protein activation (1 micro m
      mastoparan), hyperosmotic stress (150 mm NaCl) and membrane depolarization (50 mm
      KCl) were used to stimulate PLD, as monitored by the accumulation in 5 min of its
      unique transphosphatidylation product phosphatidylbutanol (PBut). In each case,
      PBut's fatty acid composition specifically matched that of
      phosphatidylethanolamine (PE), identifying this lipid as PLD's favoured
      substrate. This conclusion was substantiated by analysing the molecular species
      by electrospray ionization-mass spectrometry (ESI-MS/MS), which revealed that PE
      and NaCl-induced PBut share a unique (18 : 1)2-structure. The fatty acid
      composition of PA was much more complex, reflecting the different contributions
      from the PLC/DGK and PLD pathways. During KCl-induced stress, the PA rise was
      largely accounted for by PLD activity. In contrast, PLD's contribution to
      hyperosmotic stress-induced PA was less, being approximately 63% of the total
      increase. This was because the PLC/DGK pathway was activated as well, resulting
      in phosphoinositide-specific fatty acids and molecular species in PA.

PMID- 12787243
TI  - Sequence-based alignment of sorghum chromosome 3 and rice chromosome 1 reveals
      extensive conservation of gene order and one major chromosomal rearrangement.
AB  - The completed rice genome sequence will accelerate progress on the identification
      and functional classification of biologically important genes and serve as an
      invaluable resource for the comparative analysis of grass genomes. In this study,
      methods were developed for sequence-based alignment of sorghum and rice
      chromosomes and for refining the sorghum genetic/physical map based on the rice
      genome sequence. A framework of 135 BAC contigs spanning approximately 33 Mbp was
      anchored to sorghum chromosome 3. A limited number of sequences were collected
      from 118 of the BACs and subjected to BLASTX analysis to identify putative genes
      and BLASTN analysis to identify sequence matches to the rice genome. Extensive
      conservation of gene content and order between sorghum chromosome 3 and the
      homeologous rice chromosome 1 was observed. One large-scale rearrangement was
      detected involving the inversion of an approximately 59 cM block of the short arm
      of sorghum chromosome 3. Several small-scale changes in gene collinearity were
      detected, indicating that single genes and/or small clusters of genes have moved
      since the divergence of sorghum and rice. Additionally, the alignment of the
      sorghum physical map to the rice genome sequence allowed sequence-assisted
      assembly of an approximately 1.6 Mbp sorghum BAC contig. This streamlined
      approach to high-resolution genome alignment and map building will yield
      important information about the relationships between rice and sorghum genes and
      genomic segments and ultimately enhance our understanding of cereal genome
      structure and evolution.

PMID- 12787244
TI  - The anticodon and the D-domain sequences are essential determinants for plant
      cytosolic tRNA(Val) import into mitochondria.
AB  - In higher plants, one-third to one-half of the mitochondrial tRNAs are encoded in
      the nucleus and are imported into mitochondria. This process appears to be highly
      specific for some tRNAs, but the factors that interact with tRNAs before and/or
      during import, as well as the signals present on the tRNAs, still need to be
      identified. The rare experiments performed so far suggest that, besides the
      probable implication of aminoacyl-tRNA synthetases, at least one additional
      import factor and/or structural features shared by imported tRNAs must be
      involved in plant mitochondrial tRNA import. To look for determinants that direct
      tRNA import into higher plant mitochondria, we have transformed BY2 tobacco cells
      with Arabidopsis thaliana cytosolic tRNA(Val)(AAC) carrying various mutations.
      The nucleotide replacements introduced in this naturally imported tRNA correspond
      to the anticodon and/or D-domain of the non-imported cytosolic tRNA(Met-e).
      Unlike the wild-type tRNA(Val)(AAC), a mutant tRNA(Val) carrying a methionine CAU
      anticodon that switches the aminoacylation of this tRNA from valine to methionine
      is not present in the mitochondrial fraction. Furthermore, mutant tRNAs(Val)
      carrying the D-domain of the tRNA(Met-e), although still efficiently recognized
      by the valyl-tRNA synthetase, are not imported any more into mitochondria. These
      data demonstrate that in plants, besides identity elements required for the
      recognition by the cognate aminoacyl-tRNA synthetase, tRNA molecules contain
      other determinants that are essential for mitochondrial import selectivity.
      Indeed, this suggests that the tRNA import mechanism occurring in plant
      mitochondria may be different from what has been described so far in yeast or in
      protozoa.

PMID- 12787245
TI  - Two cis-acting elements necessary and sufficient for gibberellin-upregulated
      proteinase expression in rice seeds.
AB  - In germinating rice seeds, a cysteine proteinase (REP-1), synthesized in aleurone
      layer cells, is a key enzyme in the degradation of the major storage protein,
      glutelin. The expression of the gene for REP-1 (Rep1) is induced by gibberellins
      (GAs) and repressed by abscisic acid (ABA). To identify GA-responsive elements in
      the Rep1 promoter, we developed a transient expression system in rice aleurone
      cells. Deletion and point-mutation analyses indicated that the GA-response
      complex was composed of TAACAGA, TAACGTA, and two copies of CAACTC. The two
      former sequences were identical to GAREs conserved in the promoter of genes for
      alpha-amylase and proteinases in cereals. The latter, termed as CAACTC regulatory
      elements (CAREs), were novel GAREs. Gain-of-function experiments revealed that
      two pairs of GARE and CARE were necessary and sufficient to confer GA
      inducibility. The sequences were also required for effective transactivation by
      the transcription factor OsGAMyb. Four copies of either GARE or CARE showed
      transactivation neither by OsGAMyb nor by GA induction. CARE and GARE were also
      found in the promoters of a rice alpha-amylase gene, RAmy1A, and a barley
      proteinase gene, EPB1, which are expressed in germinating seeds. Mutations of
      CARE in their promoters caused a loss of GA inducibility and GAMyb
      transactivation, suggesting that CARE is the regulatory element for GA-inducible
      expression of hydrolase genes in the germinating seeds.

PMID- 12787246
TI  - A C-terminal sequence of soybean beta-conglycinin alpha' subunit acts as a
      vacuolar sorting determinant in seed cells.
AB  - In maturing seed cells, many newly synthesized proteins are transported to the
      protein storage vacuoles (PSVs) via vesicles unique to seed cells. Vacuolar
      sorting determinants (VSDs) in most of these proteins have been determined using
      leaf, root or suspension-cultured cells apart from seed cells. In this study, we
      examined the VSD of the alpha' subunit of beta-conglycinin (7S globulin), one of
      the major seed storage proteins of soybean, using Arabidopsis and soybean seeds.
      The wild-type alpha' was transported to the matrix of the PSVs in seed cells of
      transgenic Arabidopsis, and it formed crystalloid-like structures. Some of the
      wild-type alpha' was also transported to the translucent compartments (TLCs) in
      the PSV presumed to be the globoid compartments. However, a derivative lacking
      the C-terminal 10 amino acids was not transported to the PSV matrix, and was
      secreted out of the cells, although a portion was also transported to the TLCs.
      The C-terminal region of alpha' was sufficient to transport a green fluorescent
      protein (GFP) to the PSV matrix. These indicate that alpha' contains two VSDs:
      one is present in the C-terminal 10 amino acids and is for the PSV matrix; and
      the other is for the TLC (the globoid compartment). We further verified that the
      C-terminal 10 amino acids were sufficient to transport GFP to the PSV matrix in
      soybean seed cells by using a transient expression system.

PMID- 12787247
TI  - A polyglycine stretch is necessary for proper targeting of the protein
      translocation channel precursor to the outer envelope membrane of chloroplasts.
AB  - Toc75 is a protein translocation channel in the outer envelope membrane of
      chloroplasts and its presence is essential for the biogenesis of the organelles.
      Toc75 is the only protein identified so far in the outer membrane of chloroplasts
      or mitochondria that is synthesized as a larger precursor, preToc75, with a
      bipartite transit peptide. Its N-terminus targets the protein to the stroma and
      is removed by the stromal processing peptidase, whereas its C-terminus mediates
      envelope targeting and is removed by a yet unknown peptidase. Several conserved
      domains have been identified in the C-terminal portion of the preToc75 transit
      peptide from six plant species. We evaluated their importance in the biogenesis
      of Toc75 by means of deletion or site-directed mutagenesis, followed by import
      experiments using isolated chlroplasts. Among the conserved domains, a
      polyglycine stretch was found to be necessary for envelope targeting.
      Substitution of this domain with other stretches of a single amino acid such as
      alanine caused mistargeting of the protein into the stroma, indicating an
      important role for this domain. Furthermore, a glutamate at +2 and two alanine
      residues at -3 and -1 to the second cleavage site were found to be important for
      processing. A potential mechanism for the biogenesis of Toc75 is discussed.

PMID- 12787248
TI  - Fungal responsive fatty acid acetylenases occur widely in evolutionarily distant
      plant families.
AB  - The fungal elicitor-induced ELI12 gene from parsley has been previously shown to
      encode a divergent form of the Delta12-oleic acid desaturase. In this report, we
      show that the ELI12 gene product is a fatty acid acetylenase or a triple-bond
      forming enzyme. Expression of this enzyme in transgenic soybean seeds was
      accompanied by the accumulation of the Delta12-acetylenic fatty acids, crepenynic
      and dehydrocrepenynic acids. Using PCR with degenerate oligonucleotides, we also
      show that homologs of the ELI12 gene are present in other members of the Apiaceae
      family. In addition, cDNAs for divergent forms of the Delta12-oleic acid
      desaturase were detected among the expressed sequence tags (ESTs) from English
      ivy, an Araliaceae species, and sunflower, an Asteraceae species. As with the
      ELI12 gene, expression of these cDNAs in transgenic soybean embryos was
      accompanied by the accumulation of crepenynic and dehydrocrepenynic acids.
      Homologs of the sunflower acetylenase gene were also detected in other Asteraceae
      species, as revealed by PCR analysis of isolated genomic DNA. Results from
      Northern blot and EST analyses indicated that the expression of the sunflower
      gene, like ELI12, was induced by fungal elicitation. Overall, these results
      demonstrate that expressed genes for Delta12-fatty acid acetylenases occur in at
      least three plant families, and are responsive to fungal pathogenesis. Natural
      products derived from crepenynic and dehydrocrepenynic acids that display
      antifungal, insecticidal, and nematicidal properties are distributed through at
      least 15 plant families. The acetylenases described here provide probes for
      chemotaxonomists, and facilitate functional genomic and molecular investigations
      of these defensive mechanisms.

PMID- 12787249
TI  - AtNRAMP3, a multispecific vacuolar metal transporter involved in plant responses
      to iron deficiency.
AB  - Metal homeostasis is critical for the survival of living organisms, and metal
      transporters play central roles in maintaining metal homeostasis in the living
      cells. We have investigated the function of a metal transporter of the NRAMP
      family, AtNRAMP3, in Arabidopsis thaliana. A previous study showed that AtNRAMP3
      expression is upregulated by iron (Fe) starvation and that AtNRAMP3 protein can
      transport Fe. In the present study, we used AtNRAMP3 promoter beta-glucoronidase
      (GUS) fusions to show that AtNRAMP3 is expressed in the vascular bundles of
      roots, stems, and leaves under Fe-sufficient conditions. This suggests a function
      in long-distance metal transport within the plant. Under Fe-starvation
      conditions, the GUS activity driven by the AtNRAMP3 promoter is upregulated
      without any change in the expression pattern. We analyze the impact of AtNRAMP3
      disruption and overexpression on metal accumulation in plants. Under Fe
      sufficient conditions, AtNRAMP3 overexpression or disruption does not lead to any
      change in the plant metal content. Upon Fe starvation, AtNRAMP3 disruption leads
      to increased accumulation of manganese (Mn) and zinc (Zn) in the roots, whereas
      AtNRAMP3 overexpression downregulates Mn accumulation. In addition,
      overexpression of AtNRAMP3 downregulates the expression of the primary Fe uptake
      transporter IRT1 and of the root ferric chelate reductase FRO2. Expression of
      AtNRAMP3::GFP fusion protein in onion cells or Arabidopsis protoplasts shows that
      AtNRAMP3 protein localizes to the vacuolar membrane. To account for the results
      presented, we propose that AtNRAMP3 influences metal accumulation and IRT1 and
      FRO2 gene expression by mobilizing vacuolar metal pools to the cytosol.

PMID- 12787251
TI  - Enhanced ethylene responsiveness in the Arabidopsis eer1 mutant results from a
      loss-of-function mutation in the protein phosphatase 2A A regulatory subunit,
      RCN1.
AB  - Ethylene signaling in Arabidopsis begins with a family of five ethylene receptors
      that regulate the activity of the Raf-like kinase, CTR1. Recent work to identify
      novel factors required for modulating ethylene signaling resulted in the
      isolation of enhanced ethylene response 1 (eer1), a mutant that displays both
      increased sensitivity and increased amplitude of response to ethylene. Molecular
      cloning of eer1 reveals that its mutant phenotype results from a loss-of-function
      mutation in the previously characterized RCN1, one of three PP2A A regulatory
      subunits in Arabidopsis. Our analysis shows that neither RCN1 expression nor PP2A
      activity is regulated by ethylene. Instead, we found that Arabidopsis PP2A-1C, a
      PP2A catalytic subunit previously characterized as interacting with RCN1,
      associates strongly with the kinase domain of CTR1 in vitro. This likely
      represents a role for PP2A in modulation of CTR1 activity because an in vitro
      kinase assay did not reveal phosphorylation of either RCN1 or PP2A-1C by CTR1,
      indicating that neither of them is a substrate for CTR1. PP2A activity is
      required for Ras-dependent activation of mammalian Raf, with reductions in PP2A
      activity significantly compromising the effectiveness of this mechanism. Our
      genetic and biochemical results suggest that a similar requirement for PP2A
      activity exists for ethylene signaling, with loss-of-function mutations affecting
      PP2A activity possibly reducing the effectiveness of CTR1 activation, thus
      lowering the threshold required for manifestation of ethylene response.

PMID- 12787252
TI  - Functional analysis of the 37 kDa inner envelope membrane polypeptide in
      chloroplast biogenesis using a Ds-tagged Arabidopsis pale-green mutant.
AB  - To study the functions of the nuclear genes involved in chloroplast development,
      we systematically analyzed albino and pale-green Arabidopsis thaliana mutants by
      using a two-component transposon system based on the Ac/Ds element of maize as a
      mutagen. One of the pale-green mutants, albino or pale green mutant 1 (designated
      as apg1), did not survive beyond the seedling stage, when germinated on soil. The
      chloroplasts of the apg1 plants contained decreased numbers of lamellae with
      reduced levels of chlorophyll. A gene encoding a 37 kDa polypeptide precursor of
      the chloroplast inner envelope membrane was disrupted by insertion of the Ds
      transposon in apg1. The 37 kDa protein had partial sequence similarity to the S
      adenosylmethionine-dependent methyltransferase. The apg1 plants lacked
      plastoquinone (PQ), suggesting that the APG1 protein is involved in the
      methylation step of PQ biosynthesis, which is localized at the envelope membrane.
      Our results demonstrate the importance of the 37 kDa protein of the chloroplast
      inner envelope membrane for chloroplast development in Arabidopsis.

PMID- 12787253
TI  - Dominant repression of target genes by chimeric repressors that include the EAR
      motif, a repression domain, in Arabidopsis.
AB  - The redundancy of genes for plant transcription factors often interferes with
      efforts to identify the biologic functions of such factors. We show here that
      four different transcription factors fused to the EAR motif, a repression domain
      of only 12 amino acids, act as dominant repressors in transgenic Arabidopsis and
      suppress the expression of specific target genes, even in the presence of the
      redundant transcription factors, with resultant dominant loss-of-function
      phenotypes. Chimeric EIN3, CUC1, PAP1, and AtMYB23 repressors that included the
      EAR motif dominantly suppressed the expression of their target genes and caused
      insensitivity to ethylene, cup-shaped cotyledons, reduction in the accumulation
      of anthocyanin, and absence of trichomes, respectively. This chimeric repressor
      silencing technology (CRES-T), exploiting the EAR-motif repression domain, is
      simple and effective and can overcome genetic redundancy. Thus, it should be
      useful not only for the rapid analysis of the functions of redundant plant
      transcription factors but also for the manipulation of plant traits via the
      suppression of gene expression that is regulated by specific transcription
      factors.

PMID- 12787254
TI  - Activation tagging, a novel tool to dissect the functions of a gene family.
AB  - In a screen for morphological mutants from the T1 generation of approximately 50
      000 activation-tagging lines, we isolated four dominant mutants that showed
      hyponastic leaves, downward-pointing flowers and decreased apical dominance. We
      designated them isoginchaku (iso). The iso-1D and iso-2D are allelic mutants
      caused by activation of the AS2 gene. The T-DNAs were inserted in the 3'
      downstream region of AS2. Iso-3D and iso-4D are the other allelic mutants caused
      by activation of the ASL1/LBD36 gene. These two genes belong to the AS2 family
      that is composed of 42 genes in Arabidopsis. The only recessive mutation isolated
      from this gene family was of AS2, which resulted in a leaf morphology mutant.
      Applying reverse genetics using a database of activation-tagged T-DNA flanking
      sequences, we found a dominant mutant that we designated peacock1-D (pck1-D) in
      which the ASL5/LBD12 gene was activated by a T-DNA. The pck1-D mutants have lost
      apical dominance, have epinastic leaves and are sterile. These results strongly
      suggest that activation tagging is a powerful mutant-mining tool especially for
      genes that make up a gene family.

PMID- 12787256
TI  - The enteric nervous system II: gastrointestinal functions.
AB  - The enteric nervous system is involved in most of the physiological and
      pathophysiological processes in the gastrointestinal tract. This Minireview is
      part two of three and describes the role of the enteric nervous system in
      gastrointestinal functions (motility, exocrine and endocrine secretions, blood
      flow, and immune processes) in health and some disease states. In this context,
      the functional importance of the enteric nervous system for food intake, the gall
      bladder, and pancreas will be addressed. In specific, dysmotility, diarrhoea,
      constipation, non-occlusive intestinal ischaemia (intestinal angina),
      inflammation, cholelithiasis, cholecystitis, postcholecystectomy syndrome, and
      pancreatitis can be treated with neuroactive pharmacological agents. For example,
      serotonin receptor type four agonists can be used for the treatment of
      constipation, while nitric oxide synthesis inhibitors can be employed for the
      treatment of intestinal angina.

PMID- 12787257
TI  - Neuroprotective effects of currently used antidotes in tabun-poisoned rats.
AB  - The neuroprotective effects of antidotes (atropine, pralidoxime/atropine,
      obidoxime/atropine and HI-6/atropine mixtures) on rats poisoned with tabun at a
      lethal dose (220 microg/kg intramuscularly; 100% of LD50 value) were studied. The
      tabun-induced neurotoxicity was monitored using a functional observational
      battery and an automatic measurement of motor activity. The neurotoxicity of
      tabun was monitored at 24 hr and 7 days after tabun challenge. The results
      indicate that atropine alone is not able to protect the rats from the lethal
      effects of tabun. Three non-treated tabun-poisoned rats and one tabun-poisoned
      rat treated with atropine alone died within 24 hr. On the other hand, atropine
      combined with all tested oximes allows all tabun-poisoned rats to survive at
      least 7 days following tabun challenge. Obidoxime combined with atropine seems to
      be the most effective antidotal treatment for the elimination of tabun-induced
      neurotoxicity in the case of lethal poisoning among tested antidotal mixtures.
      The antidotal mixture consisting of atropine and HI-6 is significantly less
      effective than the combination of atropine with obidoxime in the elimination of
      tabun-induced neurotoxicity in rats at 24 hr following tabun challenge.
      Pralidoxime in combination with atropine appears to be practically ineffective to
      decrease tabun-induced neurotoxicity at 24 hours as well as 7 days following
      tabun poisoning. Due to its neuroprotective effects, obidoxime seems to be the
      most effective and most suitable oxime for the antidotal treatment of acute tabun
      exposure among currently used oximes. Thus, the replacement of obidoxime by a
      more effective acetylcholinesterase reactivator for soman poisoning, the oxime HI
      6, can to a small extent diminish the neuroprotective efficacy of antidotal
      treatment in the case of acute tabun poisonings.

PMID- 12787258
TI  - Analysis of adenosine vascular effect in isolated rat aorta: possible role of
      Na+/K+-ATPase.
AB  - The present experiments were undertaken in order to examine the effect of
      adenosine in isolated rat aorta, to investigate the possible role of intact
      endothelium and endothelial relaxing factors in this action and to determine
      which population of adenosine receptors is involved in rat aorta response to
      adenosine. Adenosine (0.1-300 microM) produced concentration-dependent (intact
      rings: pD2=4.39+/-0.09) and endothelium-independent (denuded rings: pD2=4.52+/
      0.12) relaxation of isolated rat aorta. In the presence of high concentration of
      K+ (100 mM) adenosine-evoked relaxation was significantly reduced (maximal
      relaxation in denuded rings: control - 92.1+/-9.8 versus K+- 54.4+/-5.0). Similar
      results were obtained after incubation of ouabain (100 microM) or glibenclamide
      (1 microM). In K+-free solution, K+ (1-10 mM)-induced rat aorta relaxant response
      was significantly inhibited by ouabain (100 microM). Application of indomethacin
      (10 microM), NG-nitro-L-arginine (10 microM) or tetraethylammonium (500 microM)
      did not alter the adenosine-elicited effect in rat aorta. 8-(3-Chlorostyril)
      caffeine (0.3-3 microM), a selective A2A-receptor antagonist, significantly
      reduced adenosine-induced relaxation of rat aorta in a concentration-dependent
      manner (pKB=6.57). Conversely, 1,3-dipropyl-8-cyclopentylxanthine (10 nM), an A1
      receptor antagonist, did not affect adenosine-evoked dilatation. These results
      indicate that in isolated rat aorta, adenosine produces endothelium-independent
      relaxation, which is most probably dependent upon activation of smooth muscle
      Na+/K+-ATPase, and opening of ATP-sensitive K+ channels, to a smaller extent.
      According to receptor analysis, vasorelaxant action of adenosine in rat aorta is
      partly induced by activation of smooth muscle adenosine A2A receptors.

PMID- 12787250
TI  - Sperm cells of Zea mays have a complex complement of mRNAs.
AB  - Although double fertilization in angiosperm was discovered in 1898, we still know
      nothing about the proteins that mediate gamete recognition and fusion in plants.
      Because sperm are small and embedded within the large vegetative cell of the
      pollen grain, mRNAs from sperm are poorly represented in EST databases. We
      optimized fluorescence-activated cell sorting (FACS) in order to isolate Zea mays
      sperm free of contaminating vegetative cell cytoplasm, and constructed a cDNA
      library. Sequencing of over 1100 cDNAs from the unamplified library revealed that
      sperm have a diverse complement of mRNAs. Most transcripts were singletons; the
      most abundant was sequenced only 17 times. About 8% of the sequences are
      predicted to encode secreted or plasma membrane-localized proteins and are
      therefore candidates that might mediate gamete interactions. About 8% of the
      sequences correspond to retroposons. Plant sperm have condensed chromatin and are
      thought to be transcriptionally inactive. We used RT-PCR and in situ
      hybridization to determine when selected sperm mRNAs were transcribed. Sperm
      transcripts encoding proteins involved in general cell functions were present
      throughout pollen development and were more abundant in tricellular pollen than
      in sperm cells, suggesting that these transcripts were also present in the larger
      vegetative cell. However, several transcripts, which encode proteins that are
      most similar to hypothetical Arabidopsis proteins, appeared to be present
      exclusively in the sperm cells inside mature pollen, but were already present in
      unicellular microspores. This suggests that certain transcripts might be
      transcribed early during pollen development and later partitioned into the sperm
      cells.

PMID- 12787259
TI  - Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1
      [3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).
AB  - The present study evaluated the relationship between the degree of catechol-O
      methyltransferase (COMT) inhibition in erythrocytes and liver by BIA 3-202 (1
      [3,4-dihydroxy-5-nitrophenyl]-2-phenyl-ethanone) and determined its effects upon
      the O-methylation of L-DOPA in rats orally treated with L-DOPA plus benserazide.
      The soluble form of COMT (S-COMT) in erythrocytes was endowed with the same
      affinity as liver S-COMT for the substrate adrenaline. BIA 3-202 inhibited
      erythrocytes and liver S-COMT with ED50's of 1.9 (0.7, 3.1) and 1.9 (0.5, 3.2)
      (95% confidence limits) mg kg(-1), respectively. BIA 3-202 reduced the L-DOPA
      induced rise of 3-O-methyl-L-DOPA in the peripheral circulation, striatal
      dialysate levels and striatum, and increased dopamine striatal levels. In BIA 3
      202-treated rats the increase in L-DOPA in peripheral blood and striatal
      dialysates was significantly greater than in vehicle-treated rats. It is
      concluded that S-COMT activity in erythrocytes may provide important information
      on the pharmacodynamic profile of COMT inhibitors. The novel COMT inhibitor BIA 3
      202 is a potent COMT inhibitor that enhances the availability of L-DOPA to the
      brain by reducing its O-methylation, which may prove beneficial in patients with
      Parkinson's disease treated with L-DOPA.

PMID- 12787260
TI  - Comparative pharmacokinetics and pharmacodynamics of intravenous and oral nefopam
      in healthy volunteers.
AB  - To determine the pharmacokinetic, subjective effects of a single 20 mg dose of
      nefopam administered either intravenously or orally in healthy volunteers, twenty
      four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous
      infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week
      interval, in a double-blind, double-dummy cross-over study. Nefopam and desmethyl
      nefopam plasma concentrations were measured by HPLC with UV detection up to 48 hr
      after drug administration. Self-rating questionnaires (Mood and vigilance Visual
      Analogue Scales, Addiction Research Centre Inventory) and drug safety were
      investigated. The F value (bioavailability) of the parent drug was 0.36+/-0.13.
      The AUCoral/AUCiv ratio of nefopam+desmethyl-nefopam was 0.62+/-0.23. The half
      life of nefopam was similar whether administered orally (5.1+/-1.3 hr) or
      intravenously (5.1+/-0.6 hr). The half-life of desmethyl-nefopam was two to three
      times longer than that of the parent molecule (orally: 10.6+/-3.0 versus 5.1+/
      1.3 hr, P<10(-4) and intravenously: 15.0+/-2.4 versus 5.1+/-0.6 hr, P<10(-4)). As
      assessed by the Addiction Research Centre Inventory, no evidence of abuse
      liability in healthy, drug-naive volunteers was observed. On visual analogue
      scales, volunteers rated themselves as more drowsy, less alert, less energetic
      and less anxious after oral compared to intravenous administration. The AUC0-->24
      hr of anxiety and energy parameters were not different after oral and intravenous
      administration: 90+/-142 versus 35+/-84 (P=0.27) and 66+/-74 versus 46+/-54 mm x
      hr (P=0.36), respectively. The AUC0-->24 hr of drowsiness and alertness
      parameters were significantly greater after oral than after intravenous
      administration: 68+/-65 versus 27+/-30 (P=0.005) and 54+/-63 versus 28+/-48 mm x
      hr (P=0.03), respectively. A clockwise hysteresis loop was observed for
      drowsiness in 16 out of 24 volunteers after oral administration. The results
      suggest that in healthy volunteers desmethyl-nefopam may contribute to the
      pharmacodynamic effects of single dose nefopam solution administered orally. This
      study shows a rather low bioavailability of nefopam given in intravenous solution
      when administered orally. Nevertheless, when the main metabolite desmethyl
      nefopam is taken into account, the ratio of the areas under the curves is almost
      doubled.

PMID- 12787261
TI  - Paclitaxel (taxol) inhibits the arylamine N-acetyltransferase activity and gene
      expression (mRNA NAT1) and 2-aminofluorene-DNA adduct formation in human bladder
      carcinoma cells (T24 and TSGH 8301).
AB  - Acetylator polymorphism in man results from differential expression of human
      liver N-acetyltransferase. N-Acetyltransferase enzyme activity has been
      demonstrated to be involved in some types of chemical carcinogenesis. Paclitaxel
      (taxol) had been shown to affect N-acetyltransferase activity of human lung
      cancer cells. In this study, paclitaxel was chosen to investigate the effects of
      arylamine N-acetyltransferase activity (N-acetylation of substrate), gene
      expression and 2-aminofluorene-DNA adduct formation in human bladder carcinoma
      cell lines (T24 and TSGH 8301). The N-acetyltransferase activity (N-acetylation
      of substrates) was determined by high performance liquid chromatography assaying
      for the amounts of acetylated 2-aminofluorene and p-aminobenzoic acid and
      nonacetylated 2-aminofluorene and p-aminobenzoic acid. Intact human bladder
      carcinoma T24 and TSGH 8301 cells were used for examining N-acetyltransferase
      activity, gene expression and 2-aminofluorene-DNA adduct formation. The results
      demonstrated that the N-acetyltransferase activity, gene expression (NAT1 mRNA)
      and 2-aminofluorene-DNA adduct formation in intact human bladder carcinoma cells
      were inhibited and decreased by paclitaxel in a dose-dependent manner. The
      effects of paclitaxel on the apparent values of Km and Vmax of N
      acetyltransferase enzyme from intact human bladder carcinoma cells were also
      determined in these cell lines. A marked influence of paclitaxel was observed on
      the decreasing apparent values of Km and Vmax from intact human bladder carcinoma
      cells (T24 and TSGH 8301). Thus, paclitaxel is an uncompetitive inhibitor to the
      NAT enzyme.

PMID- 12787263
TI  - Modified rice bran beneficial for weight loss of mice as a major and acute
      adverse effect of Cisplatin.

PMID- 12787262
TI  - Gene expression of cytochrome P450 1B1 and 2D6 in leukocytes in human pregnancy.
AB  - We investigated the influence of human pregnancy on gene expression of two
      cytochrome P450 enzymes in white blood cells. Cytochrome P450 1B1 (CYP1B1)
      catalyses oestradiol 4-hydroxylation, and may participate in the endocrine
      regulation of oestrogens. Cytochrome P450 2D6 (CYP2D6) metabolises many commonly
      used drugs, and previous studies have suggested that it is induced during
      pregnancy. CYP1B1 and CYP2D6 were therefore considered to be of interest in human
      pregnancy. As it is not ethically possible to take liver biopsies from healthy
      mothers during pregnancy, easily accessible cells that express the genes were
      used as a surrogate tissue. White blood cells were collected from eighteen
      pregnant women, and were used to measure CYP1B1 and CYP2D6 ribonucleic acid
      (RNA). The analysis was repeated after pregnancy, the women, thus, serving as
      their own controls. Real-time reverse transcriptase - polymerase chain reaction
      methods were used with 18S ribosomal RNA as an internal control. A slight, but
      not significant, increase in gene activity of CYP1B1 was detected during
      pregnancy. Expression of CYP2D6 in blood was extremely low, and induction of
      CYP2D6 during pregnancy could not be confirmed. In conclusion, gene expression of
      CYP1B1 and CYP2D6 in leukocytes was not significantly up-regulated in the third
      trimester of pregnancy, but a trend indicating an altered metabolism during
      pregnancy was detected.

PMID- 12787264
TI  - Genital carriage of human papilloma virus (HPV) DNA in prepubertal girls with and
      without vulval disease.
AB  - Human papilloma virus (HPV) can reach a child's anogenital area by vertical
      transmission or by close contact, which can be either sexual or nonsexual. Our
      objective was to compare HPV in prepubertal girls with and without lichen
      sclerosus (LS). We compared the frequencies and types of HPV in girls with LS
      with those in children with non-LS vulval disease (vulval swab and urine) and in
      children with no known vulval disease (urine only). HPV DNA was detected using a
      nested polymerase chain reaction (PCR) with general and consensus primers
      amplifying a region of the L1 gene, and PCR amplicons were typed using reverse
      hybridization with labeled HPV type-specific probes. Specimens untypeable by this
      method were typed by DNA sequencing. In the cohort of children with LS, we
      recorded the presence of maternal anogenital warts or a dysplastic cervical smear
      within 3 years of the affected child's birth. We found that HPV was present in
      the urine and vulval swabs of 8 of 32 children with LS and in 2 of 31 children
      with non-LS vulval disease, but also in the urine of 7 of 29 controls. In those
      with LS, the frequency was not increased significantly, but the types were
      predominantly those commonly associated with dysplasia of the cervix, penis,
      vulva, and anus, as opposed to the broader spectrum of types found in the control
      group, not all dysplasia associated. Two of the 32 mothers reported warts, and 15
      of 32 (46.9%) had an abnormal smear. (The national average of abnormal cervical
      smears is less than 10%.) We concluded that HPV appears to be common in all
      prepubertal girls, but children with LS carried types associated with dysplasia
      and their mothers had had a high incidence of dyskaryotic smears.

PMID- 12787265
TI  - Palmar-plantar keratoderma of Unna Thost associated with atopic dermatitis: an
      underrecognized entity?
AB  - We report six cases of palmar-plantar keratoderma of Unna Thost (PPKUT)
      associated with atopic dermatitis. All had typical features of PPKUT with
      diffuse, yellowish thickening on the palms and soles with a well-defined
      erythematous rim of demarcation on the sides associated with palmar-plantar
      hyperhidrosis. The changes were obvious since birth or arose during early life,
      and were persistent. We believe that the association between the two disorders is
      not coincidental but an underrecognized entity that may shed light on the
      underlying pathogenesis of these two conditions.

PMID- 12787266
TI  - Presence of vascular anomalies with congenital hemihypertrophy and Wilms tumor:
      an evidence-based evaluation.
AB  - Congenital hemihypertrophy is an uncommon condition of unknown etiology
      characterized by unilateral overgrowth of part or all of one side of the body.
      Hemihypertrophy is known to be associated with certain childhood tumors, most
      notably Wilms tumor (or nephroblastoma), and for this reason infants with
      hemihypertrophy are often followed with serial abdominal ultrasounds. Klippel
      Trenaunay syndrome (KTS) is the triad of port-wine stain, venous varicosities,
      and soft tissue and/or bony hypertrophy. Children with KTS typically have
      localized rather than generalized hemihypertrophy, but occasionally the
      hypertrophy is more extensive than the vascular anomaly itself. Information is
      lacking about whether hemihypertrophy in this setting can also be a risk factor
      for Wilms tumor. We systematically reviewed the medical literature to determine
      whether well-documented cases of Wilms tumor in the setting of both
      hemihypertrophy and vascular anomalies have been described, and if found, whether
      the association was sufficiently frequent that routine screening for Wilms tumor
      in this setting should be recommended. A review of case reports and case series
      in the pediatric population was undertaken using specific inclusion and exclusion
      criteria. We found 4 of 58 subjects with hemihypertrophy and Wilms tumor had a
      reported vascular anomaly, but in only one case was a clear-cut diagnosis of KTS
      confirmed. The relationship of the other three vascular anomalies reported was of
      uncertain significance. In conclusion, our review suggests that the risk of Wilms
      tumor in the setting of localized soft-tissue hypertrophy in conjunction with a
      vascular malformation is quite low. More extensive hemihypertrophy extending to
      body sites remote from the vascular malformation itself could have a higher risk
      of Wilms tumor, although the magnitude of this risk is uncertain. Our findings
      suggest that routine serial abdominal ultrasounds in patients with vascular
      malformations in association with localized soft-tissue hypertrophy are
      unwarranted.

PMID- 12787267
TI  - Epidemiology of childhood vitiligo: a study of 625 patients from north India.
AB  - To study the clinical and epidemiologic profile of childhood vitiligo, we
      retrospectively analyzed the data of children with vitiligo attending the
      pigmentary clinic of our center. Of the 625 children seen over 10 years, 357
      (57.1%) were girls and 268 (42.9%) were boys. As compared to adult patients with
      vitiligo, this sex difference was found to be statistically significant (p <
      0.001). The mean age of onset of the disease was 6.2 years. Vitiligo vulgaris
      (generalized vitiligo) was the most common type, followed by focal, segmental,
      acrofacial, mucosal, and universal, in that order. The most frequent site of
      onset was the head and neck, followed by the lower limbs, trunk, upper limbs, and
      mucosae. Leukotrichia was present in 77 patients (12.3%), while Koebner
      phenomenon was observed in 71 patients (11.3%). Halo nevi were observed in 29
      patients (4.4%). Seventy-six patients (12.2%) had a family history of vitiligo.
      Eight patients (1.3%) had an associated autoimmune disease. These associated
      disorders were alopecia areata in two patients, and diabetes mellitus, thyroid
      disease, Addison disease, polyglandular syndrome, and pemphigus vulgaris in one
      patient each.

PMID- 12787268
TI  - Two girls with necrobiosis lipoidica and type I diabetes mellitus with
      transfollicular elimination in one girl.
AB  - Necrobiosis lipoidica (NL) is a rare disorder that usually appears in the lower
      extremities and it is often related with diabetes mellitus (DM). There are few
      reported cases of NL in children. Transfollicular elimination of necrotic
      material has been described in adult patients with NL diabeticorum. Here we
      describe two new cases of NL in two girls with type I diabetes mellitus (DM). One
      of the cases is the first case, to our knowledge, of transfollicular elimination
      in a girl. The other case is the second case reported of lesions on the arms in a
      child with DM.

PMID- 12787269
TI  - Granular parakeratosis in children: case report and review of the literature.
AB  - Granular parakeratosis is a cutaneous eruption with erythematous and/or brownish
      hyperkeratotic papules and plaques which are exclusively localized to
      intertriginous areas and show histopathologic features of an unusual form of
      parakeratosis. The etiology is unknown, but the excessive use of various topical
      preparations (e.g., ointments and deodorants) has been associated with this
      disease. It has heretofore been reported only in adults. We report two children,
      ages 3 and 5 months, with characteristic lesions in the groin associated with
      topical pomades used to prevent diaper rash. This is the first report associating
      the clinical presentation and the histopathologic diagnosis of granular
      parakeratosis in children. The literature on this entity is also reviewed and all
      case reports are summarized.

PMID- 12787270
TI  - Sacral hemangioma with sinus tract in an infant.
AB  - Congenital midline cutaneous lesions should always alert the clinician to the
      possibility of spinal dysraphism. These lesions can take many different forms.
      The physician should be cognizant of such lesions in order to avoid potential
      neurologic complications. We present a patient with a midline sacral hemangioma
      associated with a congenital enteric sinus cyst, a previously unreported
      association.

PMID- 12787271
TI  - Calcinosis cutis following liver transplantation in a pediatric patient.
AB  - We report the occurrence of calcinosis cutis in a 3-year-old girl after liver
      transplantation. The cutaneous lesions consisted of 5 mm white papules on an
      erythematous base in linear and rosette configurations that developed in the
      abdominal and lumbar areas 10 days after transplantation. The patient had
      received calcium chloride solution intravenously during surgery. We excluded
      other causes of ectopic calcification such as hyperparathyroidism, renal failure,
      and extravasation of calcium solution. We discuss the etiology of calcinosis
      cutis after liver transplantation. This sequence of events has not been
      previously described in pediatric patients.

PMID- 12787272
TI  - A case of congenital mucinous nevus: a connective tissue nevus of the
      proteoglycan type.
AB  - Mucinous nevus is a very rare entity and can be classified as both a cutaneous
      mucinosis (CM) and a connective tissue nevus (CTN). We describe the
      clinicopathologic features of an unusual case of mucinous nevus in a 14-year-old
      Korean boy who presented with zosteriform plaques of congenital onset.

PMID- 12787273
TI  - Cutaneous pustular leukemoid reactions in trisomy 21.
AB  - We report two neonates with Down syndrome and postnatal leukemoid reactions who
      developed acute widespread pustular eruptions. The white blood cell (WBC) counts
      on the first day of life were markedly elevated, with blasts seen on examination
      of the peripheral blood smear. The skin eruptions progressed and became pustular.
      Viral and bacterial cultures were negative. Skin examination revealed pustules on
      an erythematous base on the cheeks, shoulders, trunk, and proximal extremities.
      Skin biopsy specimens showed an intraepidermal pustule with an inflammatory
      infiltrate including neutrophils, eosinophils, and mononuclear cells. The
      mononuclear cells had atypical, immature-appearing nuclei. In patient 1, these
      cells were strongly myeloperoxidase positive on immunohistochemistry, indicating
      myeloid lineage. In patient 2, these cells were CD3-positive T cells. Patient 1
      received a 5-day infusion of continuous cytarabine (ara-C) secondary to high WBC
      counts and symptomatic hyperviscosity. During therapy, the high WBC count and the
      pustules resolved. The lesions of patient 2 improved with topical mometasone
      furoate and resolved as her WBC count decreased. Recently, similar cases have
      been reported. Transient myeloproliferative disorders, or leukemoid reactions,
      should always be considered when newborns with Down syndrome or trisomy 21
      mosaicism develop a pustular eruption.

PMID- 12787274
TI  - Paraneoplastic pemphigus with bronchiolitis obliterans in a child.
AB  - Paraneoplastic pemphigus (PNP) is a rare blistering autoimmune disease associated
      with an underlying neoplasm, mucous membrane erosions, and occasionally
      bronchiolitis obliterans. Most cases have been reported in adults and the number
      of childhood cases in the current literature is limited. We describe a young
      patient with PNP who was initially misdiagnosed as having recurrent Stevens
      Johnson syndrome. This patient had an underlying inflammatory myofibroblastic
      tumor and subsequently developed fatal progressive bronchiolitis obliterans.

PMID- 12787275
TI  - Dystrophic epidermolysis bullosa inversa with COL7A1 mutations and absence of GDA
      J/F3 protein.
AB  - Epidermolysis bullosa dystrophica inversa (DEB-I) is a very rare disease
      characterized by autosomal recessive inheritance that causes blistering and
      erosions on the trunk and extremities occurring in early infancy with a
      predilection for flexural and mucosal areas thereafter. Ultrastructural findings
      show dermolytic blistering and absent or rudimentary anchoring fibrils as in
      generalized forms of dystrophic epidermolysis bullosa. Immunoreactivity for type
      VII collagen, however, is preserved. We present two patients with DEB-I with
      compound heterozygosity for the two different COL7A1 mutations, one of them
      (Arg2069Cys in exon 74) carried by the heterozygous mother, the other one
      (Lys142Arg in exon 3) carried by the heterozygous father, accompanied by absence
      of the associated anchoring fibrils protein GDA-J/F3.

PMID- 12787276
TI  - Melanocyte stimulation in focal dermal hypoplasia with unusual pigmented skin
      lesions: a histologic and immunohistochemical study.
AB  - Focal dermal hypoplasia (FDH) or Goltz syndrome is a rare genodermatosis
      transmitted in a dominant, X-linked mode. It is characterized clinically by
      atrophic skin lesions, multiple mucocutaneous papillomas, hyperpigmented linear
      skin lesions, and several skeletal and visceral anomalies. We followed over
      several years a female patient with FDH, who had the characteristic atrophic
      cutaneous lesions and periorificial papillomas, who developed at the periphery of
      atrophic lesions peculiar lentigo-like pigmented macules. Immunohistologically,
      increased melanin deposits within the epidermis and the dermis were seen,
      produced by stimulated epidermal melanocytes expressing the HMB-45 antigen. These
      findings further support the contention that cutaneous lesions of FDH may be
      progressive, and provide a physiopathologic basis for understanding the
      hyperpigmented lesions of FDH.

PMID- 12787277
TI  - Generalized acanthosis nigricans in an otherwise healthy young child.
AB  - Acanthosis nigricans in children is usually a benign condition most commonly
      associated with obesity. Generalized acanthosis nigricans is a very rare
      condition, especially in childhood. We report a 6-year-old boy with a 4-year
      history of generalized hyperpigmentation and velvety thickening of the skin.
      Despite an extensive examination, no evidence for an underlying neoplastic or
      endocrinologic disease was found.

PMID- 12787278
TI  - Complications of subcutaneous fat necrosis of the newborn: a case report and
      review of the literature.
AB  - Subcutaneous fat necrosis of the newborn is an uncommon, self-limited
      panniculitis of neonates. Rare complications such as hypercalcemia,
      thrombocytopenia, hypertriglyceridemia, and hypoglycemia have been reported. We
      describe the first case where all of the above complications were encountered in
      the same infant. Physicians caring for infants with subcutaneous fat necrosis of
      the newborn should be aware of the above associations in order to provide prompt
      and appropriate treatment to prevent associated, undesirable sequelae.

PMID- 12787279
TI  - Congenital acantholytic dyskeratotic dermatosis: localized Darier disease or
      disseminated benign papular acantholytic dermatosis?
AB  - Acantholytic dyskeratosis is a histopathologic pattern defined by a
      hyperkeratotic and parakeratotic epidermis with intraepidermal clefts containing
      acantholytic and dyskeratotic keratinocytes. These typical features are
      distinctive but not entirely pathognomonic of Darier disease, since they may
      occur at cutaneous and mucocutaneous sites in other conditions such as Grover
      disease, acantholytic and dyskeratotic epidermal nevus (nevus of Starink), warty
      dyskeratoma, or acantholytic papular dermatosis localized to the vulvocrural
      area. We report a newborn girl who had congenital erosive papules and plaques
      located on the left thigh, left ankle, and right side of the neck.
      Histopathologic examination of a punch biopsy specimen disclosed findings typical
      of acantholytic dyskeratosis. In the absence of any family history or other
      manifestations of Darier disease, we propose the descriptive term "congenital
      acantholytic dyskeratotic dermatosis." This descriptor characterizes our
      patient's disease on the basis of the clinical and histopathologic findings and
      facilitates recognition of this condition until a putative genetic mutation can
      be demonstrated or ruled out.

PMID- 12787280
TI  - Microvenular hemangioma in a boy with acute myelogenous leukemia.
AB  - Microvenular hemangioma (MVH) is a rare, benign, acquired vascular tumor. We
      report a case that shows the characteristic histopathologic features of this
      disorder in a boy with acute myelogenous leukemia (AML), suggesting an
      association with systemic immunosuppression.

PMID- 12787281
TI  - Immunotherapy for recalcitrant warts in children using intralesional mumps or
      Candida antigens.
AB  - Intralesional injection of mumps and Candida skin test antigens has been shown to
      be effective in the treatment of warts. Warts are generally difficult to treat in
      children. To determine the efficacy of intralesional skin test antigen injection
      for the treatment of resistant warts in children, we treated 47 pediatric
      patients with one or more warts with intralesional injection of mumps or Candida
      skin test antigen into one wart. Twenty-two patients (47%) with resistant warts
      experienced complete resolution of treated warts. An average of 3.78 treatments
      were necessary. An additional 34% of children had a greater than 25% improvement
      in their warts. Sixty-eight percent of subjects with more than one wart also
      noted at least partial resolution (greater than 25% resolution) of untreated
      warts at distant sites, with 34% experiencing complete resolution. We concluded
      that intralesional injection of skin test antigens is an effective therapy for
      children who have recalcitrant, nongenital, cutaneous warts.

PMID- 12787282
TI  - What syndrome is this? Greither syndrome.

PMID- 12787283
TI  - Morphea-like plaque in childhood.

PMID- 12787284
TI  - Ken and Katie caterpillar: helpful props for treatment of molluscum contagiosum.
AB  - A hand-made prop that aids in the efficient treatment of molluscum contagiosum
      with curettage or cantharidin is described. Small bandages or pieces of tape are
      affixed to a tongue depressor prior to the procedure so that they may be placed
      quickly over the treated molluscum. This improves time management and helps to
      reduce patient anxiety.

PMID- 12787287
TI  - Rheumatism: a variant of non-Langerhans cell histiocytoses?

PMID- 12787288
TI  - Infants with tinea capitis: experience from the GKT Medical School mycology
      department.

PMID- 12787290
TI  - The hygiene hypothesis.

PMID- 12787292
TI  - Unconventional and conventional medicine: who should learn from whom?
AB  - Unconventional methods are increasingly used to treat allergic diseases. This
      article identifies various factors influencing physicians and patients in their
      choice of treatment and therapist. It is often difficult for patients and
      physicians to distinguish between the natural course of disease and the effects
      of medical intervention. The 'placebo-effect' as well as other mechanisms may
      contribute to the therapeutic success. Chances and risks of unconventional
      methods are discussed. However, only by considering controlled studies can
      conventional and unconventional diagnostic and therapeutic methods be advocated
      on the basis of evidence rather than ideology.

PMID- 12787293
TI  - Fatty acids in breast milk of allergic and non-allergic mothers: The PIAMA birth
      cohort study.
AB  - Fatty acid composition was studied in breast milk of allergic and non-allergic
      mothers, focusing in particular on concentrations of the n-6 and n-3 long-chain
      polyunsaturates (LCP) in relation to maternal allergy. Milk samples were obtained
      from 168 mothers with asthma or inhalant allergies and 107 mothers without asthma
      and inhalant allergies, between 2 and 35 weeks after delivery. Mean values of
      fatty acid concentration (weight% of total fatty acids) were estimated for
      individual fatty acids, for groups of fatty acids and for the metabolic index
      (the ratio between the sum of n-6 polyunsaturates and linoleic acid). For the
      most relevant fatty acids, the association with maternal allergy was subsequently
      analyzed in more detail using multiple regression analysis. The metabolic index
      in breast milk was significantly lower in the allergic than in the non-allergic
      mothers, but no significant differences were observed in the concentrations of
      any of the n-6 fatty acids. Also concentrations of the n-3 fatty acids and nearly
      all other fatty acids were similar in allergic and non-allergic mothers' breast
      milk. No differences in fatty acid concentrations were observed between mothers
      with asthma and mothers with single or with multiple inhalant allergies. Our data
      suggest that differences in fatty acid composition between breast milk of
      allergic and non-allergic mothers are small and are unlikely to be responsible
      for the differential effects of breastfeeding by allergic and non-allergic
      mothers that have been observed in some studies.

PMID- 12787294
TI  - T-cell signal transduction in children with cow's milk allergy -- increased MAP
      kinase activation in patients with acute symptoms of cow's milk allergy.
AB  - The precise immune mechanisms behind cow's milk allergy (CMA) are still unknown.
      Previously, the production of the cytokines TNF-alpha and IFN-gamma in T cells
      from children with CMA has been shown to be decreased, and the production of IL-4
      has been shown to be increased when compared to healthy children. As these
      aberrations in cytokine production may be associated with disturbances in
      cellular function, we investigated whether T-cell signal transduction is abnormal
      in children with CMA. For this purpose we evaluated the activation of the MAP
      kinase Erk2. Thirty-nine infants were included in the study. Of those with CMA,
      13 had acute symptoms and 9 were free of symptoms due to a successful elimination
      diet at the time of the study. To activate T cells and to stimulate MAP kinase
      phosphorylation, peripheral blood mononuclear cells (PBMC) were incubated with
      Concanavalin A (ConA). The change in MAP kinase phosphorylation was measured by
      Western blotting. The increase in MAP kinase phosphorylation after stimulation
      with ConA for 5 min was significantly higher in cells from patients with acute
      symptoms of CMA than in cells from CMA patients free of symptoms or cells from
      healthy children. A time-course experiment showed that the change in MAP kinase
      phosphorylation was still increasing after 10 min incubation in cells from
      patients with acute symptoms of CMA. The increased MAP kinase activation was
      found to correlate positively with non-IgE mediated CMA in patients with acute
      symptoms of CMA.

PMID- 12787295
TI  - Expression of the T-cell markers CD2 and CD28 in healthy and atopic children
      during the first 18 months of life.
AB  - Atopy may be associated with a reduced T-cell function early in life,
      particularly regarding maturation of Th1 responses. The T-cell surface molecules
      CD2 and CD28 are involved in important T-cell activation pathways. Stimulation
      via the CD2 receptor increases the responsiveness to interleukin (IL)-12, which
      is a potent inducer of Th1 responses, whereas CD28 stimulation is critical for
      Th2 differentiation. Our aim was to prospectively study the expression of the
      cell-surface markers CD2 and CD28 on T-cells in relation to development of atopic
      disease. Children (n = 172) were followed from birth to 18 months and the
      cumulative history of atopic disease was recorded. Blood samples were obtained at
      birth and at 18 months, and in a subgroup of 78 infants also at 3, 6 and 12
      months. Flow cytometry was used to analyze the T-cell markers CD2 and CD28, the
      latter also within the subsets of T-helper (CD4+) and T-cytotoxic (CD8+) cells.
      At 18 months, 31 children had and 118 did not have atopic symptoms. At this age,
      skin prick test (SPT) positive children with atopic symptoms with or without an
      atopic family history (AFH) showed a lower expression of CD2 mode fluorescence
      intensity (FI) as well as a lower proportion of CD2+ cells, as compared with non
      sensitized children with neither atopic symptoms nor AFH. This was accompanied by
      a higher expression of CD28 FI on CD2+CD8+CD28+ cells. No significant differences
      were seen at time points before 18 months, although the proportion of CD2+ tended
      to be low also earlier in life. In conclusion, the observed reduced expression of
      CD2 in atopic infants may support previous findings that atopy is associated with
      a reduced CD2 function. The high CD28 FI in SPT positive children with atopic
      symptoms may possibly be a consequence of a TH2-skewed immune system.

PMID- 12787296
TI  - The prevalence, characteristics of and early life risk factors for eczema in 10
      year-old children.
AB  - Eczema is a common infantile disease but its nature and extent during later
      childhood remains unclear. In a whole-population birth cohort study (n = 1456) we
      examined prevalence and characteristics of eczema amongst 10-year-old children.
      At this age 1373 (94%) children completed ISAAC questionnaires, 1043 (72%) skin
      prick testing and 953 (65%) serum inhalant IgE antibody screening. At 10 years of
      age prevalence of eczema ever was 41.0% and for current eczema was 13.7%
      (combined current itchy rash and eczema ever). Most current eczema (71.0%) began
      before 4 years of age, but was associated with low morbidity at 10 years. Amongst
      children with diagnosed eczema at 4 years of age, 56.3% had current eczema at 10
      years. Atopy (positive skin test) and other allergic states were associated with
      current eczema (p < 0.001). Risk factor analysis for current eczema identified
      independent significance for atopy (p = 0.01), rhinitis (p = 0.04) and food
      allergy (p = 0.01) at 4 years, plus maternal asthma (p = 0.03). Diagnosed
      rhinitis at 4 years emerged as a significant predictor of persistent disease.
      Eczema is not simply a transient infantile condition but a common problem at 10
      years of age, often reflecting persistent disease from early childhood. Inherited
      predisposition towards atopy is the predominant risk factor for this state.

PMID- 12787297
TI  - Asthma, lung function and allergy in 12-year-old children with very low birth
      weight: a prospective study.
AB  - We assessed the relationship between very low birth weight (VLBW) (<or=1500 g)
      and the development of asthma, lung function and atopy. The study groups
      comprised 74 of all 86 (86%) VLBW and 64 of all 86 (74%) matched term children
      who were prospectively followed for 12 years. A questionnaire on asthmatic and
      allergic symptoms was completed and skin prick tests, spirometry and hypertonic
      saline provocation tests were performed at 12 years of age. Cytokine secretion
      was analysed in stimulated blood leukocyte cultures in 28 VLBW and 23 term
      children. A history of asthma was more frequent among the VLBW children, as
      compared with the term children at age 12 (22% vs. 9%, p = 0.046). Among the VLBW
      children, very preterm birth (gestational age: week 25 to 29) (RR 2.5, 95%CI 1.1
      5.8), neonatal mechanical ventilation (RR 2.8, 95%CI 1.2-6.4) and neonatal oxygen
      supplementation (RR 4.3, 95%CI 1.3-14.0) were significantly associated with a
      history of asthma by the age of 12 years in univariate analyses. In multivariate
      logistic regression, neonatal oxygen supplementation >or= 9 days was the only
      remaining significant risk factor for a history of asthma (adjusted OR 6.7, 95%CI
      1.0-44). The VLBW children who required mechanical ventilation during the
      neonatal period were more likely to have bronchial hyperresponsiveness than those
      not requiring mechanical ventilation (60% vs. 28%, p = 0.050). The spirometric
      values were similar among the VLBW and the term children at 12 years. Very low
      birth weight was not significantly related to allergic rhinoconjunctivitis,
      eczema or positive skin prick tests. Furthermore, the levels of IL-4, IL-5 and
      IFN-gamma in stimulated cell cultures were similar in the VLBW and the term
      children. A history of asthma by 12 years of age was twice as common among the
      VLBW as the term children, and neonatal oxygen supplementation seemed to be
      associated with the increased risk. Furthermore, mechanical ventilation during
      the neonatal period was associated with bronchial hyperresponsiveness at age 12.
      Very low birth weight per se was not, however, related to atopy.

PMID- 12787298
TI  - Correction of bronchial challenge data for age and size may affect the results of
      genetic association studies in children.
AB  - Meaningful studies of asthma genetics require careful definition of airway
      hyperresponsiveness (AHR). In children, several studies have emphasized the need
      for correction of bronchial challenge data for baseline parameters, such as age,
      gender, lung function and atopic status, when undertaking airway responsiveness
      measurements. However, few studies have suggested how this should be performed in
      practice. This study describes a method for the correction of dose-response
      slopes (DRS) and PC20 values for baseline parameters in children, and illustrates
      the effect of such corrections on the association of AHR with the glutathione S
      transferase GSTP1 Ile105Val polymorphism in children. Skin prick and methacholine
      challenge testing, measurement of total serum IgE concentration and GSTP1
      genotyping were performed in 145 unrelated British children aged 7-18 years.
      Correction of bronchial challenge results, expressed as both DRS and PC20 values,
      for age, gender, baseline lung function and atopic status was performed using
      linear regression and discriminant analysis, respectively. Adjusting bronchial
      challenge results for the age and size of the child altered AHR status, defined
      as a PC20 methacholine <8 mg/ml, in 37% of children. Correction for baseline
      parameters also resulted in a significant reduction in mean DRS (original
      uncorrected DRS 83.6, corrected DRSc 27.4). This had a marked effect on the
      results of the association study, unmasking a previously unidentified association
      between the GSTP1 genotype and AHR in children. Age and size adjustment of
      bronchial challenge data has a significant effect on AHR status and may influence
      the results of genetic association studies in children.

PMID- 12787299
TI  - Skin reactivity to histamine and to allergens in unselected 9-year-old children
      living in Poland and Italy.
AB  - Several studies have shown a higher prevalence of positive skin-prick tests to
      airborne allergens in Western than in Eastern European countries. We have
      recently reported that skin histamine reactivity significantly increased in Italy
      over the past 15 years. Population differences in skin histamine reactivity
      could, at least in part, explain the reported differences in positive allergen
      skin tests. To test this hypothesis we compared histamine skin reactivity and the
      prevalence of allergen positive skin-prick tests in a sample of Italian and
      Polish schoolchildren. A total of 336 unselected 9-year-old-schoolchildren (198
      in Italy and 138 in Poland) underwent skin-prick tests with three different
      histamine concentrations (10, 1 and 0.2 mg/ml) and with a panel of common
      airborne allergens according to the ISAAC protocol, phase two. Mean wheals
      elicited by skin-prick tests with the three serial concentrations of histamine
      were significantly larger (p < 0.001) and shifted more toward higher values (p <
      0.001) in Italian than in Polish children. The differences were greater for the
      intermediate histamine concentration tested (1 mg/ml) than for the highest
      concentration (10 mg/ml). Skin-prick tests for airborne allergens were more
      frequently positive in Italian children: wheals >or= 3 mm induced by any allergen
      [odds ratio (OR) 1.69; confidence interval (CI) 0.98-2.92] by Dermatophagoides
      pteronyssinus (OR 1.92; CI 0.97-3.80) and by D. farinae (OR 3.15; CI 1.16-8.63).
      Labeling as positive allergen wheal reactions half the size of the 10 mg/ml
      histamine wheal or larger reduced but did not abolish the Italian-Polish
      differences. The significantly higher skin histamine reactivity observed in
      Italian children could help to explain why allergen skin-test reactions differ in
      the East and West European populations. Moreover, differences in nonallergen
      specific factors among populations should be considered in the interpretation of
      skin test results (e.g. cut-off points). To obtain meaningful results,
      epidemiological studies of allergies should include serial histamine dilutions.

PMID- 12787300
TI  - H1-antihistaminic activity of cetirizine and fexofenadine in allergic children.
AB  - The clinical pharmacology of H1-antihistamines has not yet been optimally studied
      in children and other special groups of patients. Our objective was to determine
      the onset, extent, and duration of H1-antihistaminic activity of cetirizine and
      fexofenadine in the pediatric population. We performed a prospective, randomized,
      placebo-controlled, double-blind, crossover, single-dose study of these H1
      antihistamines in 15 allergic children, mean+/-SEM age 8.8+/-0.5 years. We used
      suppression of the histamine-induced wheal and flare as the primary outcome.
      Compared with pre-dose baseline, cetirizine 10 mg suppressed the wheals
      significantly (p<or=0.05) from 2 to 24 h and the flares significantly from 1 to
      24 h, achieving 77+/-SEM 10% to 86+/-9% suppression of the wheal from 2 to 7 h
      and 85+/-6% to 88+/-6% suppression of the flare from 2 to 24 h, inclusive.
      Compared with baseline, fexofenadine 30 mg did not suppress the wheals or flares
      significantly at any time, achieving 40+/-9% to 54+/-9% wheal suppression from 2
      to 7 h and 45+/-11% to 68+/-9% flare suppression from 2 to 7 h, inclusive.
      Compared with placebo, cetirizine suppressed the wheals and flares significantly
      from 2 to 24 h. Compared with placebo, fexofenadine suppressed the wheals
      significantly at 4 and 6 h, and the flares from 4 to 7 h. Cetirizine suppressed
      the wheals and flares significantly more than fexofenadine at 2 h (wheals), and
      at 3 and 24 h (flares). Placebo did not suppress the wheals and flares
      significantly at any time. In children age 6-11 years, cetirizine 10 mg has a
      rapid onset of H1-antihistaminic activity, a 24-h duration of action, and greater
      H1-activity than fexofenadine 30 mg. Higher doses of fexofenadine should be
      tested in children.

PMID- 12787301
TI  - The effect of montelukast on allergen-induced cutaneous responses in house dust
      mite allergic children.
AB  - The benefits of a leukotriene modifier on allergen-induced cutaneous responses
      have not been studied in children. We hypothesized that a leukotriene-receptor
      antagonist would provide protection against allergen-induced early and/or late
      phase cutaneous responses in susceptible children. In a randomized, double-blind,
      placebo-controlled, cross-over study in 6- to 15-year-old house dust mite
      allergic children, we compared the benefit of either montelukast or a matching
      placebo for 2 days on cutaneous responses induced by intradermal injection of
      house dust mite extract. Responses were measured as the mean of the longest
      diameter and its longest perpendicular of the induration response after 10, 20
      min, 4 h and 6 h of the challenge. A total of 30 children were randomized to
      placebo or montelukast. The mean decline from baseline was significantly greater
      (p = 0.04) in the montelukast-treated children [-5.20 mm (-12.03-1.63)][median
      (95% CI)] than in the placebo-treated children [0.13 mm (-6.46-6.73] at 6th hour
      of the challenge, as was the mean diameter (p = 0.04), but did not differ in the
      remaining time points. We concluded that in house dust mite allergic children,
      montelukast 5 mg provided significant improvement in allergen-induced cutaneous
      late-phase responses, suggesting its contribution to allergic skin responses and
      its potential therapeutic value.

PMID- 12787302
TI  - Immunomodulation during sublingual therapy in allergic children.
AB  - The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated,
      but its mechanism of action is still controversial. The most recent experimental
      observations suggest that a critical role in the modulation of immune response is
      sustained by Th2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, by co
      stimulatory molecules, such as CD40 on B cells, and by hormones and
      neuropeptides. To better understand whether SLIT affects immune responses we used
      a double-blind placebo-controlled design. Eighty-six children with mild asthma
      due to allergy to Dermatophagoides pteronyssinus (33 of whom also had
      rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We
      assessed symptom scores using diary cards of each patient and determined the
      expression of CD40 on B cells and the serum concentration of ECP, IL-13,
      prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed
      a significant reduction in asthma and rhinitis scores in the immunotherapy group
      compared with the placebo group, no variation in CD40 and ACTH, but a significant
      decrease in ECP, IL-13 and PRL after 6 months of therapy (p <0.01). Our results
      confirm the efficacy and safety of SLIT, and lead us to believe that it could
      modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL-13.
      In addition, the reduction of PRL might be a signal of reduced activation of T
      lymphocytes.

PMID- 12787303
TI  - Early acquisition of serum and saliva antibodies reactive to enteropathogenic
      Escherichia coli virulence-associated proteins by infants living in an endemic
      area.
AB  - Enteropathogenic Escherichia coli (EPEC) is the most common etiological agent of
      acute diarrhea among infants living in poor social conditions in Brazil and other
      developing countries. This infection is rare in breast-fed infants, as well as in
      children older than 2 years. Over the past few years, our group has attempted to
      identify antibodies to EPEC virulence proteins in human milk and to establish the
      in vitro protective role of these antibodies. In the present study, we report the
      identification of antibodies to EPEC virulence proteins in sera and saliva from
      children of different ages, living in slums in the city of Sao Paulo, Brazil.
      Using EPEC and bacterial constructs (pET) for immunoblotting (IB) analysis,
      antibodies reacting to the main adhesins (intimin, bundle-forming pilli) and cell
      signaling proteins (EPEC secreted proteins - Esp A, Esp B) were detected in sera
      from adults and children older than 1 year. Almost all children older than 1 year
      presented recognition patterns similar to those of adults in IB assays for serum
      IgG and secretory IgA antibodies, using EPEC outer membrane and other antigenic
      preparations. As previously observed for human milk, all samples from adults and
      older children recognized the 94 kDa molecular weight adhesin intimin strongly.
      In most children, previous EPEC symptomatic diarrhea could not be confirmed;
      however, almost all of them have presented one or more diarrhea episodes during
      their lifetime. These results suggest that reduction of EPEC infection frequency
      after 2 years of age may be associated with the development of anti-EPEC antibody
      repertoires.

PMID- 12787304
TI  - Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric
      rheumatological diseases.
AB  - The tumor suppressor protein p53 plays an important role in cell cycle
      regulation. One of the major features in rheumatic diseases is the abnormal
      proliferation of lymphocytes. p53 expression in peripheral blood mononuclear
      cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore
      measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA)
      and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy
      controls, to determine their role. p53 expression in patients was insignificantly
      higher than that of controls (2.28 +/- 2.71% vs. 1.08 +/- 1.02%, respectively, p
      > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55%
      (95th percentile of controls). SLE patients with active disease had significantly
      higher p53 expression compared to controls and to patients with quiescent disease
      although no significant correlation with ESR or complement 3 was detected.
      Seropositivity to anti-p53 antibodies was observed in none of controls but in
      22.8% of patients, all of whom, except one, had active disease. Seropositivity to
      anti-p53 antibodies was more prominent in lupus nephritis than in other
      presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients
      was insignificantly higher than in seronegatives. p53 expression and
      seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not
      significantly affected by the mode of therapy. Thus, the overexpression of p53 in
      some patients with active SLE and JRA might explain the abnormal proliferation of
      autoreactive lymphocytes that perpetuates the inflammatory response. The presence
      of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with
      its regulatory functions.

PMID- 12787305
TI  - Left-handedness in asthmatic children.
AB  - Left-handedness has been associated with asthma and allergic disorders. The
      Geschwind-Behan-Galaburda (GBG) hypothesis could explain this association. In
      view of previous findings, we investigated the distribution of laterality scores
      among asthmatic children and controls aged 4-8 years old. Seventy families with
      asthmatic children were administered the International Study of Asthma and
      Allergy in Childhood (ISAAC) questionnaire and the Edinburgh Left-handedness
      Inventory. A sample of 70 families with non-asthmatic, healthy children was used
      as controls. The majority of children had mild asthma. Ambidexterity was the main
      feature in the asthmatic children. A statistically significant difference in the
      laterality quotient (LQ) distribution was found in the group of asthmatic
      children with allergic rhinitis (LQ mean value in the asthmatic children with
      allergic rhinitis: 42.85 vs. 79.50 in the rest of the asthmatic children). These
      results suggest that there is a tendency towards left-handedness in asthmatic
      children and lend support to the GBG hypothesis.

PMID- 12787306
TI  - Medical treatment reverses cytokine pattern in allergic and nonallergic chronic
      rhinosinusitis in asthmatic children.
AB  - A Th2 cytokine pattern has recently been reported both in allergic and
      nonallergic chronic rhinosinusitis in asthmatic children. The aim of the study
      was to evaluate the cytokine pattern in chronic rhinosinusitis in allergic and
      nonallergic asthmatic children before and after medical treatment. Thirty
      asthmatic children were evaluated, 18 males and 12 females (mean age 9.1 years).
      Sixteen were allergic and 14 were nonallergic. All children were asthmatic and
      suffered from chronic rhinosinusitis, whose diagnosis was confirmed by endoscopy.
      All of them were treated with amoxicilline-clavulanate (20 mg/kg b.i.d.) and
      fluticasone propionate aqueous nasal spray (100 microg daily) for 14 days; a
      short course of oral corticosteroid was also prescribed (deflazacort 1 mg/kg
      daily for 2 days, 0.5 mg/kg daily for 4 days and 0.25 mg/kg daily for 4 days).
      Rhinosinusal lavage and nasal cytology were performed in all subjects before and
      after medical treatment. IL4 and IFNgamma were measured by immunoassay and
      inflammatory cells were counted by conventional staining. Thirteen allergic
      children and 12 nonallergic children showed a negative endoscopy after the
      treatment. Allergic subjects showed a significant decrease of IL4 (p = 0.0002)
      and a significant increase of IFNgamma (p = 0.03) after the treatment.
      Nonallergic children showed a significant decrease of IL4 (p = 0.0007) and a
      nonsignificant increase of IFNgamma. A significant reduction of the inflammatory
      infiltrate was detected in all asthmatic children (p < 0.05). This study confirms
      a Th2 polarization in chronic rhinosinusitis both in allergic and nonallergic
      asthmatic children. Moreover, the medical treatment of chronic rhinosinusitis
      reversed the cytokine pattern from a Th2 towards a Th1 profile both in allergic
      and nonallergic children.

PMID- 12787308
TI  - Peculiar form of cerebral microdysgenesis characterized by white matter neurons
      with perineuronal and perivascular glial satellitosis: A study using a variety of
      human autopsied brains.
AB  - Microdysgenesis (MD) is a neuropathological term that implies a variety of minor
      developmental abnormalities of the brain. Recently, MD has been used for
      pathological diagnosis of cerebral tissues surgically resected from epileptic
      patients. However, criteria or consensus on pathological diagnosis of MD is still
      vague and controversial because of the lack of control studies. Therefore, this
      study paid special attention to the presence of white matter neurons with
      perineuronal glial satellitosis (WMN-GS) and perivascular glial satellitosis
      (PVGS) in the white matter, which are occasionally observed in epileptic foci, in
      order to clarify whether they could be handled as definite findings of MD. The
      materials included 80 autopsied whole brains ranging from normal subjects to
      patients with cerebrovascular disorder, neurodegenerative diseases and
      malformations. In each case, the presence of WMN-GS and/or PVGS was searched in
      10 gyri in all five lobes (rostral frontal lobe, caudal frontal lobe, parietal
      lobe, temporal lobe and oc-cipital lobe) and evaluated. Statistically
      significant, WMN-GS and/or PVGS preferentially appeared in a diseased group
      consisting of neuronal migration disorder and related conditions, such as
      polymicrogyria, nodular heterotopia or tuberous sclerosis, leading to a
      suggestive conclusion that the presence of WMN-GS and/or PVGS could be a peculiar
      form of MD possibly derived from neuronal migrational arrest or related events,
      even if they appear alone without any other gross abnormalities.

PMID- 12787307
TI  - Phenotypic analysis of peripheral T/NK cell lymphoma: study of 408 Japanese cases
      with special reference to their anatomical sites.
AB  - The World Health Organization (WHO) classification of malignant lymphoma
      presented a list of disease entities well defined by clinical, immunological and
      genetic features. Therefore, the current diagnosis of peripheral T/NK-cell
      lymphomas (PTNKLs) essentially requires the inclusion of anatomical sites of
      disease and phenotypical features. We analyzed 408 Japanese cases of PTNKLs in
      order to clarify the relationship between anatomical sites of disease and
      phenotypical features and to translate the functional subsets of T and NK cells
      into their diagnoses for further understanding lymphomatic biology. The T/NK-cell
      lymphoma entities were allocated into three categories: (i) cytotoxic memory T
      cell and/or NK-cell lymphoma (n = 151) consisting of extranodal NK/T-cell tumors
      other than mycosis fungoides (MF); (ii) non-cytotoxic memory T-cell lymphoma (n =
      142) consisting of nodal and cutaneous tumors such as angioimmunoblastic T-cell
      lymphoma, adult T-cell lymphoma/leukemia and MF; and (iii) anaplastic lymphoma
      kinase positive anaplastic large cell lymphoma (n = 110) that has unique features
      and might be regarded as cytotoxic 'naive' T-cell lymphoma. Overall, these three
      categories were significantly correlated with age of onset, anatomical sites, the
      level of expression of cytotoxic molecules and CD45RO, and association with
      Epstein-Barr virus. This concept might provide a new insight enabling further
      understanding of the interrelationships among WHO T/NK-cell disease entities.

PMID- 12787309
TI  - Immunohistochemical demonstration of 14-3-3 sigma protein in normal human tissues
      and lung cancers, and the preponderance of its strong expression in epithelial
      cells of squamous cell lineage.
AB  - In order to confirm 14-3-3 sigma (sigma) protein distribution in human tissues,
      immunohistochemistry was performed using various paraffin-embedded human tissues.
      In normal human tissues, the strongest immunoreactivity for 14-3-3sigma protein
      was observed in squamous epithelia at various sites, followed by basal cells of
      the trachea, bronchus and basal or myoepithelial cells of various glands.
      Moderate to weak 14-3-3sigma immunoreactivity was seen in the epithelial cells of
      the alimentary tract, gall bladder, urinary tract and endometrium. In the lung,
      14-3-3sigma immunoreactivity was also observed in hyperplastic type II alveolar
      cells and metaplastic squamous cells. Immunohistochemical study using non-small
      cell lung cancers revealed that 14-3-3sigma immunoreactivity was stronger in
      squamous cell carcinomas than in adenocarcinomas. The present study revealed that
      14-3-3sigma expression was exclusively present in various epithelial cells and
      had a tendency to be stronger in cells destined for squamous epithelium or
      differentiating toward squamous cells in human normal and neoplastic cells.

PMID- 12787310
TI  - Usefulness of endoscopic biopsy using immunostaining of p53 and Ki-67 in tumors
      of the ampulla of Vater.
AB  - We investigated the diagnostic and prognostic value of p53 expression and
      proliferative activity, as indicated by the Ki-67, in endoscopic biopsy
      specimens. Specimens were immunologically stained with p53 and MIB-1 (Ki-67), and
      the MIB-1/Ki-67 labeling index (LI) was calculated. Classification of adenomas
      was based on findings of H&E-stained preparations into those with low- or high
      grade atypia. Well-differentiated tubular and papillary adenocarcinomas were
      classified as carcinomas with low- or high-grade atypia. There were significant
      differences among the control and adenoma patients in MIB-1/Ki-67 LI (P < 0.05).
      No significant difference was identified between adenomas with high grade atypia
      and carcinomas with low grade atypia. The p53 expression was negative in all
      adenomas, but it was positive in 68.2% of carcinomas. The current study
      demonstrated that p53 protein expression in endoscopic biopsy specimens was of
      preoperative diagnostic value for carcinoma of the ampulla of Vater. The p53
      protein positive tumors had a relatively higher malignant potential than p53
      protein negative ones. The MIB-1/Ki-67 LI was useful in differentiating non
      tumorous lesions from adenomas and adenomas with low- or high-grade atypia. The
      MIB-1/Ki-67 LI had a prognostic value because clinicopathological factors of
      carcinoma of ampulla of Vater correlated with MIB-1/Ki-67 LI.

PMID- 12787311
TI  - Fibrosis and smooth muscle metaplasia in rectovaginal endometriosis.
AB  - Rectovaginal (RV) endometriosis presents with a nodular lesion composed of
      fibromuscular and endometriotic tissue, and the fibromuscular tissue is the major
      component in the severe stage. The purpose of our study was to examine the
      extending process of fibromuscular tissue in RV endometriosis. Histological
      examinations using immunostains, were performed in 90 RV tissue specimens from 37
      women. Fibrosis was present in 89 specimens. In each specimen, the intensity of
      the fibrosis differed from area to area: in mildly fibrotic areas, the collagen
      fibers were present around the endometriotic tissue, and in severely fibrotic
      areas, the fibrosis widely extended into fat and connective tissus as well as
      within the endometriotic tissue. In the 60 specimens containing endometriotic
      tissue, the increase in the amount of endometriotic tissue significantly
      correlated to the increase in degree of fibrosis in the entire tissue. The
      presence of aggregated smooth muscles, unassociated with blood vessels, was
      defined as smooth muscle metaplasia (SMM), which was always present within the
      fibrotic areas, and was observed in 80 specimens. The degree of SMM in the entire
      tissue was significantly correlated with the degree of fibrosis. From these
      findings, the following was hypothesized. Initially, endometriotic tissue was
      present sporadically and fibrosis was present around the endometriotic tissue.
      Thereafter, proliferation of endometriotic tissue and an increase in fibrosis
      occur consecutively. The SMM was present within the fibrotic areas, and it became
      more severe, correlating with the increase in fibrosis. In conclusion, this is
      the first report describing the extending process of the fibromuscular tissue of
      RV endometriosis from a histological viewpoint, and we think that recognization
      of this process is useful for histological diagnosis and clinical management of
      RV endometriosis.

PMID- 12787312
TI  - Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase
      positive cells lacking a myofibroblastic phenotype.
AB  - Inflammatory myofibroblastic tumor (IMT), synonymously referred to as
      inflammatory pseudotumor, is a distinctive mesenchymal lesion composed of spindle
      cells displaying morphological features of myofibroblasts admixed with
      considerable numbers of inflammatory cells. Recent genetic and molecular studies
      have shown that a subset of IMT is characterized by the expression of altered
      anaplastic lymphoma kinase (ALK) protein mostly resulting from rearrangements of
      the ALK gene such as TPM3-ALK, TPM4-ALK and CLTC-ALK fusion genes. We analyzed
      the ALK status in nine cases of IMT arising in various anatomical locations. Six
      cases showed immunohistochemical expression of the ALK protein, and two ALK
      positive lesions examined by reverse transcription-polymerase chain reaction and
      a subsequent sequencing analysis harbored the TPM4-ALK fusion gene. Of note, the
      majority of ALK-positive tumor cells in four of the six lesions lacked the
      coexpression of myogenic markers including alpha-smooth muscle actin, a
      cytoskeletal protein indicating myofibroblastic differentiation, whereas a
      substantial number of tumor cells in the remaining two cases coexpressed ALK and
      alpha-smooth muscle actin and/or desmin. In an ultrastructural study of the
      lesion with predominant ALK-positive/actin-negative cells, spindle cells failed
      to demonstrate features of myofibroblasts such as intracytoplasmic bundles of
      thin filaments and dense bodies. The current findings suggest that ALK-positive
      cells in IMT are not always myofibroblastic but might be immature primitive
      mesenchymal cells.

PMID- 12787313
TI  - Ataxia and male sterility (AMS) mouse. A new genetic variant exhibiting
      degeneration and loss of cerebellar Purkinje cells and spermatic cells.
AB  - We describe a novel genetic variant mouse that exhibited ataxia and male
      sterility, named the AMS mouse. It arose in autoimmune-prone MRL/lpr strain and
      putative ams mutation showed an autosomal recessive inheritance pattern. Clinical
      symptoms were first discernible at approximately 21 days of age and consisting of
      subtle sway of the trunk followed by failure to maintain still posture and
      appearance of abnormal walk, but no further worsening was noted with advancement
      of age. The abnormal motor coordination was ascribed to almost complete loss of
      Purkinje cells of the cerebellum. The cell loss in the Purkinje cell layer began
      before onset of ataxia and rapidly progressed towards near-complete loss by 6
      weeks of age. Another symptom was male sterility due to severe oligozoospermia
      associated with cellular degeneration during spermatic differentiation in the
      seminiferous tubules. Thus, the effects of the genetic variation were apparent in
      two different organs after the development of their basic histological
      structures, and degeneration and loss of particular cell types in these two
      tissues produced overt clinical symptoms. Genetic pleiotropism, provided that the
      nature of genetic variation is of a single gene mutation, is discussed.

PMID- 12787314
TI  - A new mutation, ataxia and male sterility (ams), of autoimmune-prone MRL/lpr
      mouse is not linked to lpr gene but associated with reduction of spleen size and
      alteration of lymphocyte subpopulations.
AB  - We describe changes in the immune system of the newly established mutant line,
      ataxia and male sterility (AMS) mouse, and that the putative ams mutation is
      independent of lpr but seemed to affect lymphoproliferation in its mother strain,
      MRL/lpr. The mean weights of the spleen and lymph nodes of ams-lpr double
      homozygous mouse were reduced compared with lpr single-homozygous mouse.
      Comparison between ams single-homozygous and control mice revealed 45-50%
      reduction of the spleen weight in the former for which reduction of the number of
      nucleated cells contributed greatly. In the lymphocyte/monocyte fraction of the
      spleen, there were significant changes in the proportion of lymphocyte
      subpopulations, with a reduction of B cells, an increase in CD4 and CD8 T cells,
      and a decrease in the CD4 : CD8 ratio. In vitro response of splenocytes to
      concanavalin A showed inconspicuous dose- and time-dependent responses in ams
      homozygous spleen, suggesting functional alteration of the immunological
      response. Our results indicate that ams mutation affects the immune system in
      addition to its two other major effects on the central nervous system and male
      reproductive system.

PMID- 12787315
TI  - Intra-epithelial neuroendocrine carcinoma of the nasal cavity.
AB  - We describe a distinctive neuroendocrine carcinoma (NEC) that proliferated intra
      epithelially. The tumor was 35 mm in diameter and arose from the right superior
      turbinate of a 46-year-old woman. Histologically, the tumor exhibited papillary
      growth and the tumor cells were localized in the thickened mucosal epithelium.
      The tumor cells had round to oval and vesicular or hyperchromatic nuclei, and
      cohered without any specific structure such as a fibrillary background, rosette
      or glandular structure. No stromal invasion by the tumor was observed.
      Immunohistochemically, the tumor cells were positive for neuron-specific enolase
      focally. In addition, many tumor cells expressed cytokeratin (AE1/AE3 and CAM
      5.2), mostly with characteristic perinuclear dot-like patterns. Electron
      microscopy revealed focal but well-eveloped cytoplasmic processes containing
      arrays of microtubules and a few dense core granules. The tumor was considered to
      be a poorly differentiated neuroendocrine carcinomas (NEC) that exhibited
      exceptional intra-epithelial proliferation. The tumor completely disappeared
      after the stereotactic radiosurgery and has not recurred for 40 months. It might
      be difficult to distinguish a poorly differentiated NEC in the sinonasal region
      from other neuroectodermal tumors, including olfactory neuroblastoma, but the
      differential diagnosis is important because each tumor has different
      clinicopathological characteristics.

PMID- 12787316
TI  - Desmoplastic malignant mesothelioma of the pleura: autopsy reveals asbestos
      exposure.
AB  - Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma,
      and is often difficult to distinguish from reactive pleural fibrosis because of
      associated extensive collagen fibrosis. An 82-year-old woman with a severe cough
      was revealed to have pleural effusion and diffuse pleural thickening on the right
      side. Antibiotics were ineffective, and a compression fracture of the ninth and
      tenth thoracic vertebral bodies was recognized on X-ray. Autopsy revealed a
      diffuse pleural thickening with hyalinized collagen tissue in the central part of
      the pleura. However, the peripheral part of the fibrous tissue was composed of
      spindle and polygonal cell proliferation that were immunohistochemically positive
      for antibodies against cytokeratin and vimentin. In addition, the ninth and tenth
      thoracic spines were infiltrated by similar cells. The condition was diagnosed as
      desmoplastic mesothelioma with bone metastases. Asbestos bodies were detected in
      the thickened pleura and fibrosed alveolar septa, and it was suggested
      retrospectively that the patient had been exposed to asbestos. Thus, autopsy
      analyses of fibrous pleurisy are necessary to detect a desmoplastic variant of
      mesothelioma of the pleura and its association with asbestos exposure.

PMID- 12787317
TI  - Prostatic stromal sarcoma: case report and review of the literature.
AB  - We report a case of a 65-year-old man with rare prostatic stromal sarcoma in
      which suprapubital radical prostatectomy was performed, but neither chemotherapy
      nor radiation therapy were administered before or after the operation. The well
      circumscribed tumor, measuring 5 cm in diameter, showed a homogeneous white
      grayish cut surface with a hard consistency. Histopathologically, the tumor
      consisted mainly of medium-sized rounded cells with a sarcomatous and epithelioid
      appearance intermingled with collagen fiber. Hyalinized foci were also noted in
      the tumor. Immunohistochemistry revealed that the tumor cells were diffusely
      positive for vimentin and focally positive for progesterone receptor and CD34,
      but not for EMA, cytokeratin or estrogen receptor. No recurrence or distant
      metastasis of the tumor has occurred in 8 years of follow up. The tumor was
      diagnosed as prostatic stromal sarcoma (PSS) showing epithelioid differentiation
      and of a progesterone-dependent nature. Possible favorable nature of the PSS
      might be expected after complete resection.

PMID- 12787318
TI  - Primary cholangiohepatitis as an alternative name for primary biliary cirrhosis.

PMID- 12787319
TI  - Neurotrophins and neurodegeneration.
AB  - There is growing evidence that reduced neurotrophic support is a significant
      factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's
      disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).
      In this review we discuss the structure and functions of neurotrophins such as
      nerve growth factor, and the role of these proteins and their tyrosine kinase
      (Trk) receptors in the aetiology and therapy of such diseases. Neurotrophins
      regulate development and the maintenance of the vertebrate nervous system. In the
      mature nervous system they affect neuronal survival and also influence synaptic
      function and plasticity. The neurotrophins are able to bind to two different
      receptors: all bind to a common receptor p75NTR, and each also binds to one of a
      family of Trk receptors. By dimerization of the Trk receptors, and subsequent
      transphosphorylation of the intracellular kinase domain, signalling pathways are
      activated. We discuss here the structure and function of the neurotrophins and
      how they have been, or may be, used therapeutically in AD, PD, Huntington's
      diseases, ALS and peripheral neuropathy. Neurotrophins are central to many
      aspects of nervous system function. However they have not truly fulfilled their
      therapeutic potential in clinical trials because of the difficulties of protein
      delivery and pharmacokinetics in the nervous system. With the recent elucidation
      of the structure of the neurotrophins bound to their receptors it will now be
      possible, using a combination of in silico technology and novel screening
      techniques, to develop small molecule mimetics with much improved
      pharmacotherapeutic profiles.

PMID- 12787320
TI  - APOE epsilon 4 influences the pathological phenotype of Alzheimer's disease by
      favouring cerebrovascular over parenchymal accumulation of A beta protein.
AB  - The relative amounts of amyloid beta-protein (A beta) in cerebral blood vessels
      and parenchyma vary considerably amongst patients with Alzheimer's disease (AD).
      Although several mechanisms have been proposed to explain this variability, the
      underlying genetic and environmental determinants are still unclear, as are the
      functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E
      (ApoE), influence the risk of developing AD and of deposition of A beta within
      the brain. We examined the relationship between the APOE genotype and the
      relative extent of accumulation of A beta as plaques within the cerebral
      parenchyma and in cortical blood vessels in the form of cerebral amyloid
      angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly,
      neurologically normal controls of which 19 had CAA without other
      neuropathological features of AD. In the AD cases, we also assessed whether the
      severity of CAA was related to the age of onset and duration of dementia, risk
      factors for atherosclerotic vascular disease, and histologically demonstrable
      cerebral infarcts or foci of haemorrhage. The APOE genotype was determined by a
      standard polymerase chain reaction-based method. Paraffin sections of frontal,
      temporal and parietal lobes were immunolabelled for A beta and the parenchymal A
      beta load (total A beta minus vessel-associated A beta) was quantified by
      computer-assisted image analysis. CAA severity was scored for cortical and
      leptomeningeal vessels. The relevant clinical data were obtained from the
      database of the South West Brain Bank. In AD, we found the severity of CAA to be
      strongly associated with the number of epsilon 4 alleles (P < 0.0001) but the
      parenchymal A beta load to be independent of APOE genotype. Cases with severe CAA
      had a lower parenchymal A beta load than had those with moderate CAA (P = 0.003).
      Neither the severity of CAA nor the parenchymal A beta load correlated with age
      of onset, duration of disease or age at death, and the severity of CAA also did
      not correlate with the presence of cerebral infarcts or foci of haemorrhage.
      These findings indicate that possession of the APOE epsilon 4 allele favours
      vascular over parenchymal accumulation of A beta in AD. This may influence the
      pathogenesis of neurodegeneration in epsilon 4-associated AD.

PMID- 12787321
TI  - Frontotemporal and motor neurone degeneration with neurofilament inclusion
      bodies: additional evidence for overlap between FTD and ALS.
AB  - We present the case of a patient who had clinical frontal lobe dementia without
      apparent motor neurone disease (MND), with pathologic findings not typical of any
      single currently classified frontotemporal degeneration (FTD). At autopsy, the
      brain had frontal and temporal atrophy with neuronal loss, gliosis, and
      superficial spongiosis, typical of all FTDs. There were at least three different
      morphologic types of intracytoplasmic neuronal inclusions in a variety of brain
      and brainstem regions, including the hippocampal dentate gyrus and pyramidal
      neurones, the neocortex (in particular, the motor cortex), basal ganglia,
      thalamus, subthalamic nucleus, basis pontis, and inferior olivary nuclei.
      Inclusions had the morphologies of Pick-like bodies, pleomorphic inclusions, and
      hyaline conglomerate (HC)-like inclusions. None of these were positive with tau
      immunostains. Pick-like bodies in the dentate gyrus were labelled with ubiquitin.
      The pleomorphic inclusions in the neocortex and dentate gyrus and the HC-like
      inclusions in the motor and parietal cortex were strongly positive with
      immunostains for neurofilament. We discuss the differential diagnosis and compare
      this case with those disorders to which it is most similar. In particular, we
      compare the unique neurofilament-positive inclusions to the inclusions of FTD
      MND, to Pick bodies, and to the basophilic and HC inclusions that are
      occasionally seen in amytrophic lateral sclerosis (ALS). Although FTD-MND may be
      found in ALS, the findings in this case may have additional implications for a
      link between FTD and ALS.

PMID- 12787322
TI  - Comparative genomic hybridization and pathological findings in atypical
      teratoid/rhabdoid tumour of the central nervous system.
AB  - The atypical teratoid/rhabdoid tumour (AT/RT) is an uncommon tumour of the
      central nervous system in children, characterized by the presence of a rhabdoid
      cell component associated with variable combinations of primitive neuroectodermal
      tumour, mesenchymal and epithelial differentiation. Immunohistochemistry reveals
      a complex pattern of antigen expression and cytogenetic studies have demonstrated
      losses from chromosome 22. We have performed comparative genomic hybridization
      (CGH) on paraffin-embedded material from three cases of AT/RT. Two cases showed
      losses from chromosome 22 associated with other chromosome imbalances including
      losses from 1p in both cases. The third case demonstrated a loss from 8p as the
      sole abnormality. While monosomy or deletion from chromosome 22 is a useful
      diagnostic marker for AT/RT, it is not present in all cases. The variation in
      cytogenetic patterns reported for this tumour type raises the possibility that
      different genetic pathways may underlie this tumour phenotype and warrants the
      further definition of the cytogenetic spectrum for this rare tumour.

PMID- 12787323
TI  - Comparison of the neuropathological characteristics of bovine spongiform
      encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) in mice.
AB  - Bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease
      (vCJD) belong to a group of diseases called the transmissible spongiform
      encephalopathies (TSEs). Transmission studies in inbred mice (strain typing)
      provided overwhelming evidence that vCJD arose from BSE. In this study, we
      compare the patterns of neuropathology in a panel of three inbred mouse strains
      (RIII, C57BL and VM) and one cross (C57BL x VM) infected with either vCJD or BSE.
      For each mouse strain, patterns of abnormal prion protein (PrPres) deposition,
      astrocytosis and vacuolation were similar in the vCJD- and BSE-challenged mice.
      Prion protein (PrP)-positive plaques were prominent in the VM and C57BL x VM mice
      in addition to diffuse PrPres accumulation, whereas only diffuse PrPres labelling
      was observed in the RIII and C57BL mice. The hippocampus was targeted in all
      mouse strains, as was the cochlear nucleus in the medulla, both showing
      consistent severe vacuolation and heavy PrPres deposition. Although the targeting
      of PrPres was similar in the BSE- and vCJD-infected brains, the amount and
      intensity of PrPres observed in the brains treated with formic acid during
      fixation was reduced considerably. The distribution of astrocytosis was similar
      to the targeting of PrPres deposition in the brain, although some differences
      were observed in the hippocampi of mice challenged with vCJD. We conclude that
      there are no significant differences in the targeting of neuropathological
      changes observed in the BSE- and vCJD-infected mice, consistent with the previous
      evidence of a link between BSE and vCJD.

PMID- 12787324
TI  - Expression of the interferon-induced MxA protein in viral encephalitis.
AB  - MxA protein accumulates cytoplasmically in response to interferon stimulation,
      and mediates resistance against several viruses. In order to test whether MxA may
      serve as a diagnostic tool for viral infections of the central nervous system
      (CNS), we performed MxA immunohistochemistry on biopsies and autopsies of 57
      patients with neurological disorders of known viral and nonviral aetiology. MxA
      was detectable in all HIV patients with proven opportunistic viral encephalitis,
      in all patients suffering from isolated viral encephalitis, in one of three HIV
      patients with cerebral toxoplasmosis, and in one case of micronodular
      encephalitis. No MxA was detectable in HIV patients with isolated HIV
      encephalitis or HIV infection accompanied by an opportunistic nonviral disorder.
      We were unable to show MxA expression in a variety of nonviral inflammatory and
      noninflammatory disorders of the CNS. Several cases of Rasmussen's encephalitis
      and multiple sclerosis tested negative, arguing against their possible viral
      aetiology. Two-colour immunohistochemistry identified macrophages and activated
      microglia as MxA expressing cells. In all studied cases MxA expression was
      accompanied by a marked T-cell infiltrate. Therefore, the detection of MxA
      protein is a sensitive adjuvant marker for those cases of viral encephalitis
      which are accompanied by pronounced lymphocytic infiltrates.

PMID- 12787325
TI  - Alpha-synuclein-positive structures in association with diffuse neurofibrillary
      tangles with calcification.
AB  - alpha-Synuclein is known to be a major constituent of the Lewy bodies (LBs) in
      Parkinson's disease (PD) and the neuronal and glial cytoplasmic inclusions (NCIs,
      GCIs) in multiple system atrophy. alpha-Synuclein-positive inclusions such as
      LBs, NCIs and GCIs sometimes show colocalization with tau-positive
      neurofilaments. Studies using alpha-synuclein immunohistochemistry have often
      found LBs in the amygdala of patients with familial or sporadic Alzheimer's
      disease (AD), as well as in patients with Down's syndrome and AD. However, no
      studies have reported alpha-synuclein-positive structures in cases of diffuse
      neurofibrillary tangles with calcification (DNTC), which is characterized by
      numerous neurofibrillary tangles (NFTs) throughout the cerebral cortex but few,
      if any, senile plaques. We investigated the distribution of alpha-synuclein
      positive structures in two cases of DNTC: a 65-year-old woman (brain weight, 850
      g) and a 75-year-old woman (brain weight, 800 g). In both cases, severe cerebral
      atrophy predominant in the temporal lobe was noted. Microscopically, alpha
      synuclein-positive intracytoplasmic inclusions and neurites were found in the
      superior temporal lobe (within the temporal pole), amygdala, parahippocampus,
      entorhinal cortex and insula, the regions most affected by the NFTs. alpha
      Synuclein-positive intracytoplasmic inclusions were rare or absent in other
      regions of the cerebral cortex and brainstem. This distribution pattern differs
      from that of PD or dementia with LBs. Our findings suggest that the accumulation
      pattern of alpha-synuclein is a pathological feature of DNTC, and that DNTC is
      associated with accumulation of both tau and alpha-synuclein.

PMID- 12787327
TI  - Misrouted olfactory fibres and ectopic olfactory glomeruli in normal humans and
      in Parkinson and Alzheimer patients.
AB  - The presence and distribution of misrouted (MR) olfactory projection fibres were
      studied in the olfactory bulbs of control human brains and in the brains of
      people who had suffered from Parkinson's and Alzheimer's disease. It appeared
      that MR fibres, that is, fibres that terminate deep into the glomerular layer,
      are a common phenomenon in the bulbs of aged people. In all but one of the bulbs
      studied, MR fibres are present. The amount of MR fibres is not related to age.
      With a few exceptions, the MR fibres are restricted to the external plexiform
      layer (EPL). Only in Parkinson bulbs the MR fibres occasionally form glomerulus
      like structures. These pseudo glomeruli are located in the EPL. It is concluded
      that MR olfactory projection fibres are a normal phenomenon in the human
      olfactory bulb. In nonhuman mammalians, MR fibres have only been observed in
      foetal and neonatal olfactory bulbs. Possibly, the age-related loss of mitral
      cells, which are the natural synaptic targets for the olfactory projection
      fibres, may play a role in the aberrant behaviour of the MR olfactory receptor
      cell axons. The ectopic glomerulus-like structures in Parkinson bulbs share some
      characteristics with normal rat glomeruli that are not observed in normal human
      olfactory glomeruli. This may refer to possible changes in the genetic content of
      olfactory structures in Parkinson patients.

PMID- 12787326
TI  - Pathological inclusion bodies in tauopathies contain distinct complements of tau
      with three or four microtubule-binding repeat domains as demonstrated by new
      specific monoclonal antibodies.
AB  - Pathological inclusions containing fibrillar aggregates of hyperphosphorylated
      tau protein are a characteristic feature in the tauopathies, which include
      Alzheimer's disease, frontotemporal dementia with parkinsonism linked to
      chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal
      degeneration and Pick's disease. Tau isoform composition and cellular and
      regional distribution as well as morphology of these inclusions vary in each
      disorder. Recently, several pathological missense and exon 10 splice-donor site
      mutations of the tau gene were identified in FTDP-17. Exon 10 codes for the
      second of four microtubule-binding repeat domains. The splice-site mutations
      result in increased inclusion of exon 10 which causes a relative increase in tau
      isoforms containing four microtubule-binding repeat domains over those containing
      three repeat domains. This could be a central aetiological mechanism in FTDP-17
      and, perhaps, other related tauopathies. We have investigated changes in the
      ratio and distribution of three-repeat and four-repeat tau in the different
      tauopathies as a basis of the phenotypic range of these disorders and the
      selective vulnerability of different subsets of neurones. In this study, we have
      developed two monoclonal antibodies, RD3 and RD4 that effectively distinguish
      these closely related tau isoforms. These new isoform-specific antibodies are
      useful tools for analysing tau isoform expression and distribution as well as
      pathological changes in the human brain.

PMID- 12787328
TI  - Case report: An autopsy-proven case of fulminant subacute sclerosing
      panencephalitis.

PMID- 12787329
TI  - A neurofilament antibody recognizes a subset of pyramidal cells in the human
      neocortex that are preserved in Alzheimer's disease.

PMID- 12787332
TI  - Human submucosal neurones regulate intestinal epithelial cell proliferation:
      evidence from a novel co-culture model.
AB  - The role of the human enteric nervous system (ENS) in the control of the
      intestinal epithelium organization and proliferation is unknown. To address this
      issue, we developed a novel co-culture model, consisting of human submucosa
      containing the submucosal plexus and a human colonic epithelial monolayer. After
      3 days in basal conditions (i.e. in absence of neuronal activation) epithelium
      disorganization and proliferation occurred. In contrast, electrical activation of
      submucosal neurones maintained monolayer organization and decreased cell
      proliferation. These effects were blocked by tetrodotoxin and a vasoactive
      intestinal peptide (VIP) receptor antagonist, and reproduced by VIP. In
      conclusion, our study suggests that the human ENS is involved in the control of
      epithelial cell proliferation.

PMID- 12787333
TI  - Further extension of the brain-gut axis?

PMID- 12787334
TI  - Murine intestinal migrating motor complexes: longitudinal components.
AB  - Spontaneous migrating contractions have been described in the circular muscle of
      the isolated mouse colon and terminal ileum, however, spontaneous events
      equivalent to these have not been reported in the longitudinal muscle. The
      longitudinal muscle shortenings in the colon and ileum, which are of similar
      form, frequency and pharmacology to the circular muscle colonic and ileal
      migrating motor complexes (CMMCs and IMMCs), are recorded in the present study.
      The spontaneous ileal and colonic longitudinal muscle shortenings appear to be
      neurally organized as they are abolished by tetrodotoxin (1 micro mol L-1),
      hexamethonium (500 micro mol L-1) and morphine (1 micro mol L-1). Endogenously
      released nitric oxide slowed the frequency of spontaneous ileal and colonic
      longitudinal muscle shortenings and 5-hydroxytryptamine increased their
      frequency. Hyoscine (1 micro mol L-1) abolished longitudinal shortenings in the
      ileum and reduced the amplitude of longitudinal shortening by approximately 44%
      in the colon. Shortenings were effectively abolished by nifedipine (1 micro mol L
      1). Surgical sectioning of the colon identified that each region of the colon
      contracted longitudinally in an independent fashion; the distal colon contracted
      to the greatest amplitude and lowest frequency. The longitudinal preparation is
      suitable to initially assess the actions of novel pharmacological agents on
      spontaneous, neurally coordinated, CMMCs and IMMCs in emptied isolated murine
      intestines.

PMID- 12787335
TI  - Motility in the isolated mouse colon: migrating motor complexes, myoelectric
      complexes and pressure waves.
AB  - This study has used mechanical, together with pressure/volume recordings or
      electrophysiological recordings, to investigate the spontaneous activity in
      isolated preparations of mouse colon. In the former preparations, when not
      distended with fluid, spontaneous colonic migrating motor complexes (CMMCs) were
      observed using isotonic transducers. When the colons were distended with fluid,
      CMMCs continued at an increased frequency and in addition were associated
      temporally, with rises in intraluminal pressure and pulses of distally ejected
      fluid. 5-Hydroxytryptamine (1 micro mol L-1) or NG-nitro-l-arginine (100 micro
      mol L-1) increased the frequency of propulsive activity and this activity was
      abolished by hexamethonium (500 micro mol L-1). In a second preparation,
      myoelectric complexes recorded from circular muscle cells in colons using
      intracellular microelectrodes, were found to correlate in frequency and phase
      with CMMCs. The experiments indicate that CMMCs are intimately related to
      pressure waves in the fluid-filled viscus and the muscle membrane potential
      changes that have been recorded during myoelectric complexes are likely to be
      analogous to those occurring during fluid-filled propulsive activity.

PMID- 12787336
TI  - Interdigestive small bowel motility and duodenal bacterial overgrowth in
      experimental acute pancreatitis.
AB  - The objective of this study is to investigate the effects of an acute necrotizing
      pancreatitis (ANP), without biliary obstruction, on the migrating motor complex
      (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and
      infection of the pancreas simultaneously. Rats were divided into four groups:
      mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes
      were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs
      were harvested for microbial culturing 72 h after induction of pancreatitis. The
      splenic portion of the pancreas was taken for histology. During ANP the MMC cycle
      length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P <
      0.05). The duodenum of ANP rats was in contrast with the other groups
      characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P <
      0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram
      negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle
      length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A
      positive correlation (r = 0.85, P < 0.01) was found between the severity of
      pancreatitis and duodenal bacterial overgrowth. During ANP without biliary
      obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The
      correlation between the severity of pancreatitis, the disturbance of the MMC and
      SBBO suggests an important pathophysiological role of the proximal small bowel in
      the infection of pancreatic necrosis.

PMID- 12787337
TI  - The role of the cytoskeleton in capacitative calcium entry in myenteric glia.
AB  - Capacitative calcium entry (CCE) is the process by which intracellular calcium is
      replenished from the external milieu upon depletion of intracellular stores. CCE
      is thought to participate in chemotaxis, proliferation and cell signalling. A
      physical interaction between intracellular stores and the plasma membrane is
      postulated to regulate CCE. We hypothesized that cytoskeletal disruption alters
      this interaction, inhibiting CCE in enteric glia. Cultured myenteric glia from
      neonatal guinea-pigs were treated with cytochalasin D (10 micro mol L-1), a
      microfilament disrupting agent, nocodazole (20 micro mol L-1), a microtubule
      disrupting agent, or vehicle (dimethyl sulphoxide). Intracellular calcium changes
      were measured using fura-2 microfluorimetry. To evaluate the rate of cation re
      entry, barium was substituted for calcium because barium is not sequestered
      internally. Cytochalasin D-treated glia had diminished CCE responses (57 +/- 3
      nmol L-1) compared with controls (97 +/- 7 nmol L-1) as did nocodazole-treated
      glia (30 +/- 2 nmol L-1) vs controls (77 +/- 6 nmol L-1). The proportion of cells
      demonstrating CCE abolition was greater in the cytochalasin (50 +/- 8%) and
      nocodazole-treated (89 +/- 2%) groups compared with controls (21 +/- 2%, 40 +/-
      9%, respectively). Cytochalasin D and nocodazole treatment diminished the rate of
      cation re-entry based on diminished barium entry in treated vs control cells.
      From this study, we conclude that disruption of cytoskeletal elements diminishes
      calcium influx essential to calcium store repletion in myenteric glia.

PMID- 12787338
TI  - Morphological characteristics and immunohistochemical detection of nicotinic
      acetylcholine receptors on intestinofugal afferent neurones in guinea-pig colon.
AB  - Intestinofugal afferent neurones (IFANs) provide excitatory synaptic input to
      abdominal prevertebral ganglion neurones. Input is greatly reduced during
      blockade of nicotinic acetylcholine receptors (nAChRs) in the wall of the colon,
      suggesting two projection pathways: a direct pathway without synaptic
      interruption and an indirect pathway interrupted by at least one nicotinic
      cholinergic synapse. This study aimed to characterize the morphology of IFANs and
      examine the distribution of nAChRs on them. We identified IFANs in guinea-pig
      colon by retrograde labelling with fluorescent tracer DiI placed either on the
      lumbar colonic nerves in vitro or inferior mesenteric ganglion in vivo. Confocal
      laser scanning microscopy and computerized image-processing software were used
      for 3D image reconstruction. Approximately 70% of identified IFANs had Dogiel
      type I-like morphology, the remainder were Dogiel type II-like. In vivo labelled
      IFANs were injected with Lucifer Yellow and immunostained for nAChRs using
      monoclonal antibody MAb35. Approximately 3% of total plasma membrane surface of
      IFANs with Dogiel type I morphology had MAb35-IR. In contrast, <1% of membrane
      surface of IFANs with Dogiel type II morphology had MAb35-IR. The finding that
      IFANs displayed immunostaining for nAChRs suggests the presence of putative
      nicotinic synapses.

PMID- 12787339
TI  - Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory
      responses in the isolated guinea-pig gastric fundus.
AB  - The inhibitory neurotransmission of the stomach was investigated in isolated
      guinea-pig gastric fundus. In preparations treated with guanethidine (1 micro mol
      L-1) and p-fluoro-hexahydro-sila-difenidol (1 micro mol L-1), electrical
      stimulation evoked neurogenic inhibitory responses not modified by hexamethonium
      (100 micro mol L-1), suggesting that inhibitory postganglionic non-adrenergic non
      cholinergic (NANC) nerve fibres are involved. The nitric oxide (NO)-synthase
      inhibitor Nomega-nitro-l-argininine-methyl-ester hydrochloride (1-100 micro mol L
      1) and the soluble guanylyl cyclase inhibitor ODQ (0.1-3 micro mol L-1) also
      abolished such relaxant response, suggesting the involvement of NO/Cyclic
      Guanosine 3',5' monophosphate (cGMP) system as the final mechanism of muscle
      relaxation. The alpha2-adrenoceptor agonist, UK 14 304 (10 nmol L-1-10 micro mol
      L-1) did not influence the electrical field stimulation (EFS)-evoked NANC
      responses. These latter responses were also refractory to a variety of receptor
      agonists and antagonists, acting at Gamma Aminobutyric Acid (GABA), serotonin
      5HT1a, opioid micro , delta and kappa, muscarinic M1 and M2, histamine H2 and H3
      and cannabinoid receptors. The NANC response was insensitive to the P/Q-type Ca2+
      channel blocker omega-agatoxin TK (1 nmol L-1-0.1 micro mol L-1), but partially
      inhibited by the N-type Ca2+-channel blocker omega-conotoxin GVIA (0.1 nmol L-1
      0.1 micro mol L-1), and by the L-type Ca2+-channel blockers nifedipine and
      calcicludine (0.1 nmol L-1-0.1 micro mol L-1). These data suggest that the NANC
      relaxation of the isolated guinea-pig gastric fundus is mediated by NO as the
      final inhibitory (neuro)transmitter at the longitudinal smooth muscle cells. The
      mechanism(s) promoting NO production is/are Ca2+-dependent, but apparently
      insensitive to presynaptic modulation. Both N- and L-type channels seem to occur
      in nitrergic nerve endings, where they contribute to trigger NO diffusion at the
      synaptic cleft.

PMID- 12787340
TI  - Central tumour necrosis factor-alpha mediates the early gastrointestinal motor
      disturbances induced by lipopolysaccharide in sheep.
AB  - Cytokines are involved in fever and other symptoms of the acute phase response
      induced by endotoxins. The aim of this work was to study the involvement of
      central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by
      lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body
      temperature and myoelectric activity of the antrum, duodenum and jejunum was
      recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg
      1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and
      increased the frequency of the migrating motor complex (MMC). These effects
      started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1)
      mimicked these effects when injected intracerebroventricularly (i.c.v.) but not
      i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg
      1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS.
      Furthermore, the effects induced by either LPS or TNF were suppressed by prior
      i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v.
      injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS
      disturbs GI motility in sheep through a central pathway that involves TNF-alpha
      and prostaglandins sequentially.

PMID- 12787341
TI  - Slowing of intestinal transit by fat depends on an ondansetron - sensitive,
      efferent serotonergic pathway.
AB  - The ileal brake is a neural reflex that slows proximal small bowel transit when
      fat enters the distal small bowel. In rats, ondansetron, a 5-hydroxytryptamine-3
      (5-HT3)-receptor antagonist, abolishes the ileal brake. However, the location of
      this serotonergic pathway is unknown. Of the known enteric sites responsive to 5
      hydroxytryptamine (5-HT), only the myenteric neurone is equipped with 5-HT3
      receptors and is located on the efferent limb of reflex response. The aim of this
      study was to test the hypothesis that slowing of intestinal transit by fat may
      depend on an ondansetron-sensitive serotonergic pathway located on the efferent
      limb of this reflex response. In a fistulated dog model that compartmentalized
      the afferent from the efferent limb of the ileal brake response, ondansetron was
      delivered luminally into the distal (afferent) or proximal (efferent) half of the
      small bowel to localize the serotonergic pathway. It was found that activating
      the ileal brake slowed down the proximal intestinal transit to 30% of control
      values. The ileal brake was abolished when ondansetron was delivered into the
      proximal but not the distal small bowel. Our data supports the hypothesis that
      the 5-HT receptors participating in the ileal brake are on the efferent limb of
      this neural reflex, possibly on myenteric neurones.

PMID- 12787342
TI  - Modulation of oesophago-UOS contractile reflex: effect of proximal and distal
      esophageal distention and swallowing.
AB  - Upper oesophageal sphincter (UOS) tone is influenced by intraoesophageal pressure
      events. Our aim was to test the hypothesis that UOS tone is responsive to
      simultaneous inhibitory and stimulatory signals originating from the oesophagus
      and compare effect of proximal and distal oesophageal air distention on
      oesophageal balloon-stimulated UOS contraction. We studied 16 healthy volunteers,
      ages 19-80 years in two stages. We induced UOS contraction by distending various
      size balloons intraoesophageally and studied response of contracted UOS to
      oesophageal air distentions and swallowing. Intraoesophageal injections of 60-ml
      room air resulted in UOS pressure augmentation (31%), relaxation (64%) and no
      effect in the remaining 5% of instances. The majority of air injections into the
      oesophageal segment proximal to the distended balloon were followed by relaxation
      of the contracted UOS, whereas, the majority of oesophageal air distentions
      distal to the balloon resulted in augmentation of UOS contraction (P < 0.01).
      Swallowing resulted in complete relaxation of the UOS. In conclusion, UOS
      contractile response to oesophageal balloon distention is overridden by further
      augmentation or relaxation as a result of oesophageal air distention and
      swallowing. Contractile and inhibitory responses of the contracted UOS to
      generalized oesophageal distention is region-specific.

PMID- 12787343
TI  - Interlaboratory differences in method for analysis of manometry explain
      discrepancies in studies of duodenal phase III peristalsis.

PMID- 12787345
TI  - Tracing pathways of transport protein evolution.
AB  - We have conducted bioinformatic analyses of integral membrane transport proteins
      belonging to dozens of families. These families rarely include proteins that
      function in a capacity other than transport. Many transporters have arisen by
      intragenic duplication, triplication and quadruplication events, in which the
      numbers of transmembrane alpha-helical hydrophobic segments (TMSs) have
      increased. The elements multiplied may encode two, three, four, five, six, 10 or
      12 TMSs and gave rise to proteins with four, six, seven, eight, nine, 10, 12, 20,
      24 and 30 TMSs. Gene fusion, splicing, deletion and insertion events have also
      contributed to protein topological diversity. Amino acid substitutions have
      allowed membrane-embedded domains to become hydrophilic domains and vice versa.
      Some evidence suggests that amino acid substitutions occurring over evolutionary
      time may in some cases have drastically altered protein topology. The results
      summarized in this microreview establish the independent origins of many
      transporter families and allow postulation of the specific pathways taken for
      their appearance.

PMID- 12787346
TI  - Translational repression mechanisms in prokaryotes.
AB  - Translational repression results from a complex choreography of macromolecular
      interactions interfering with the formation of translational initiation
      complexes. The relationship between the rate and extent of formation of these
      interactions to form repressed mRNA complexes determines the extent of
      repression. A novel analysis of repression mechanisms is presented here and it
      indicates that the reversibility of repressed complex formation influences the
      steady state balance of the distribution of translationally active and inactive
      complexes and therefore has an impact on the efficiency of repression. Reviewed
      here is evidence for three distinct translational repression mechanisms,
      regulating expression of the transcription factor sigma32, threonine tRNA
      synthetase and ribosomal proteins on the alpha operon in Escherichia coli.
      Efficient regulation of expression in these systems makes use of specific mRNA
      structures in quite different ways.

PMID- 12787348
TI  - Role of the Escherichia coli Tat pathway in outer membrane integrity.
AB  - The Escherichia coli Tat system serves to export folded proteins harbouring an N
      terminal twin-arginine signal peptide across the cytoplasmic membrane. Previous
      work has demonstrated that strains mutated in genes encoding essential Tat
      pathway components are highly defective in the integrity of their cell envelope.
      Here, we report the isolation, by transposon mutagenesis, of tat mutant strains
      that have their outer membrane integrity restored. This outer membrane repair of
      the tat mutant arises as a result of upregulation of the amiB gene, which encodes
      a cell wall amidase. Overexpression of the genes encoding the two additional
      amidases, amiA and amiC, does not compensate for the outer membrane defect of the
      tatC strain. Analysis of the amiA and amiC coding sequences indicates that the
      proteins may be synthesized with plausible twin-arginine signal sequences, and we
      demonstrate that they are translocated to the periplasm by the Tat pathway. A
      Tat+ strain that has mislocalized AmiA and AmiC proteins because of deletion of
      their signal peptides displays an identical defective cell envelope phenotype.
      The presence of genes encoding amidases with twin-arginine signal sequences in
      the genomes of other Gram-negative bacteria suggests that a similar cell envelope
      defect may be a common feature of tat mutant strains.

PMID- 12787347
TI  - The Escherichia coli amidase AmiC is a periplasmic septal ring component exported
      via the twin-arginine transport pathway.
AB  - The N-acetylmuramoyl-l-alanine amidases of Escherichia coli (AmiA, B and C) are
      periplasmic enzymes that remove murein cross-links by cleaving the peptide moiety
      from N-acetylmuramic acid. Ami- cells form chains, indicating that the amidases
      help to split the septal murein. Interestingly, cells defective in the twin
      arginine protein transport (Tat) pathway show a similar division defect. We find
      that both AmiA and AmiC are routed to the periplasm via Tat, providing an
      explanation for the Tat- division phenotype. Taking advantage of the ability of
      Tat to export prefolded (fluorescent) green fluorescent protein (GFP) to the
      periplasm, we sublocalized AmiA and AmiC in live cells using functional fusions
      to GFP. Interestingly, the periplasmic localization of the fusions differed
      markedly. AmiA-GFP appeared to be dispersed throughout the periplasm in all
      cells. AmiC-GFP similarly appeared throughout the periplasm in small cells, but
      was concentrated almost exclusively at the septal ring in constricting cells.
      Recruitment of AmiC to the ring was mediated by an N-terminal non-amidase
      targeting domain and required the septal ring component FtsN. AmiC therefore
      replaces FtsN as the latest known recruit to the septal ring and is the first
      entirely periplasmic component to be localized.

PMID- 12787349
TI  - The twin-arginine translocation (Tat) system is essential for Rhizobium-legume
      symbiosis.
AB  - The Tat (twin-arginine translocation) system mediates export of periplasmic
      proteins in folded conformation. Proteins transported via Tat contain a
      characteristic twin-arginine motif in their signal peptide. Genetic determinants
      (tatABC genes) of the Tat system from Rhizobium leguminosarum bv. viciae were
      cloned and characterized, and a tatBC deletion mutant was constructed. The mutant
      lacked the ability for membrane targeting of hydrogenase, a known Tat substrate,
      and was impaired in hydrogenase activity. Interestingly, in the absence of a
      functional Tat system, only small, white nodules unable to fix nitrogen were
      induced in symbiosis with pea plants. Analysis of nodule structure and location
      of green fluorescent protein (GFP)-tagged bacteria within nodules indicated that
      the symbiotic process was blocked in the tat mutant at a stage previous to
      bacteria release into cortical cells. The R. leguminosarum Tat-deficient mutant
      lacked a functional cytochrome bc1 complex. This was consistent with the fact
      that R. leguminosarum Rieske protein, a key component of the symbiosis-essential
      cytochrome bc1 complex, contained a typical twin-arginine signal peptide.
      However, comparative analyses of nodule structure indicated that nodule
      development in the tat mutant was arrested at an earlier step than in a
      cytochrome bc1 mutant. These data indicate that the Tat pathway is also critical
      for proteins relevant to the initial stages of the symbiotic process.

PMID- 12787350
TI  - Ten families of variant genes encoded in subtelomeric regions of multiple
      chromosomes of Plasmodium chabaudi, a malaria species that undergoes antigenic
      variation in the laboratory mouse.
AB  - The chromosome ends of human malaria parasites harbour many genes encoding
      proteins that are exported to the surface of infected red cells, often being
      involved in host-parasite interactions and immune evasion. Unlike other murine
      malaria parasites Plasmodium chabaudi undergoes antigenic variation during
      passage in the laboratory mouse and hence is a model suitable for investigation
      of switching mechanisms. However, little is known about the subtelomeric regions
      of P. chabaudi chromosomes and its variable antigens. Here we report 80 kb of
      sequence from an end of one P. chabaudi chromosome. Hybridization of probes
      spanning this region to two dimensional pulsed field gels of the genome revealed
      10 multicopy gene families located exclusively in subtelomeric regions of
      multiple P. chabaudi chromosomes, interspersed amongst multicopy intergenic
      regions. Hence all chromosomes share a common subtelomeric structure, presumably
      playing a similar role in spatial positioning as the P. falciparum Rep20
      sequence. Expression in blood stages, domains characteristic of surface antigens
      and copy numbers between four and several hundred per genome, indicate a
      functional role in antigenic variation for some of these families. We identify
      members of the cir family, as well as novel genes, that although clearly
      homologous to cir have large low complexity regions in the predicted
      extracellular domains. Although all families have homologues in other rodent
      Plasmodium species, four were previously not known to be subtelomeric. Six have
      homologues in human and simian malarias.

PMID- 12787351
TI  - Promoter analysis of Helicobacter pylori genes with enhanced expression at low
      pH.
AB  - To identify Helicobacter pylori genes with expression that is enhanced under low
      pH conditions, we used subtractive hybridization methodology. We identified 28
      acid-induced genes, of which 18 have known or putative functions. Six pairs of
      genes were co-transcribed. Primer extension analysis identified single or
      multiple transcriptional start points (tsp) for 14 of the 22 loci. Sequence
      analysis of the -10 regions upstream of the tsps revealed consensus motifs for
      multiple RNA polymerase sigma factors present in H. pylori (sigma80, sigma54 and
      sigma28). No sequences resembling the -35 Escherichia coli consensus sequence
      (TTGACA) were present upstream of any of the genes. Both increased gene
      transcription and decreased mRNA decay contribute to the observed increase in H.
      pylori transcript abundance at acid pH. These studies document the complex
      response of H. pylori to environmental pH changes, and provide insight into
      mechanisms used for intragastric survival.

PMID- 12787352
TI  - A reporter gene system for the hyperthermophilic archaeon Sulfolobus solfataricus
      based on a selectable and integrative shuttle vector.
AB  - Sulfolobus solfataricus has developed into an important model organism for
      molecular and biochemical studies of hyperthermophilic archaea. Although a number
      of in vitro systems have been established for the organism, efficient tools for
      genetic manipulations have not yet been available for any hyperthermophile. In
      this work, we have developed a stable and selectable shuttle vector based on the
      virus SSV1 of Sulfolobus shibatae. We have introduced pUC18 for propagation in
      Escherichia coli and the genes pyrEF coding for orotidine-5'-monophosphate
      pyrophosphorylase and orotidine-5'-monophosphate decarboxylase of Sulfolobus
      solfataricus as selectable marker to complement pyrimidine auxotrophic mutants.
      Furthermore, the beta-galactosidase gene (lacS) was introduced into this vector
      as a reporter under the control of the strong and heat-inducible promoter of the
      Sulfolobus chaperonin (thermosome). After transformation of a S. solfataricus
      pyrEF/lacS double mutant, the vector was found to reside as a single-copy vector,
      stably integrated into the host chromosome via the site-specific recombination
      system of SSV1. Specific beta-galactosidase activities in transformants were
      found to be fourfold higher than in wild-type S. solfataricus cells, and
      increased to more than 10-fold after heat shock. Greatly increased levels of lacS
      mRNA were detected in Northern analyses, demonstrating that this reporter gene
      system is suitable for the study of regulated promoters in Sulfolobus and that
      the vector can also be used for the high-level expression of genes from
      hyperthermophilic archaea.

PMID- 12787353
TI  - The DEAD-box RNA helicase SrmB is involved in the assembly of 50S ribosomal
      subunits in Escherichia coli.
AB  - Ribosome assembly in Escherichia coli involves 54 ribosomal proteins and three
      RNAs. Whereas functional subunits can be reconstituted in vitro from the isolated
      components, this process requires long incubation times and high temperatures
      compared with the in vivo situation, suggesting that non-ribosomal factors
      facilitate assembly in vivo. Here, we show that SrmB, a putative DEAD-box RNA
      helicase, is involved in ribosome assembly. The deletion of the srmB gene causes
      a slow-growth phenotype at low temperature. Polysome profile analyses of the
      corresponding cells reveal a deficit in free 50S ribosomal subunits and the
      accumulation of a new particle sedimenting around 40S. Analysis of the ribosomal
      RNA and protein contents of the 40S particle indicates that it represents a large
      subunit that is incompletely assembled. In particular, it lacks L13, one of the
      five ribosomal proteins that are essential for the early assembly step in vitro.
      Sucrose gradient fractionation also shows that, in wild-type cells, SrmB
      associates with a pre50S particle. From our results, we propose that SrmB is
      involved in an early step of 50S assembly that is necessary for the binding of
      L13. This step may consist of a structural rearrangement that, at low
      temperature, cannot occur without the assistance of this putative RNA helicase.

PMID- 12787354
TI  - Ribosome bypassing elicited by tRNA depletion.
AB  - Ribosome bypassing refers to the ability of the ribosome::peptidyl-tRNA complex
      to slide down the message without translation to a site several or dozens of
      nucleotides downstream and resume protein chain elongation there. The product is
      an isoform of a protein with a 'coding' gap corresponding to the region of the
      message which was bypassed. Previous work showed that ribosome bypassing was
      strongly stimulated at 'hungry' codons calling for a tRNA whose aminoacylation
      was limited. We have now used the 'minigene' phenomenon to ascertain whether
      depletion of the pool of specific isoacceptors has a similar effect. High level
      expression of plasmid-borne minigenes results in the sequestration as peptidyl
      tRNA of tRNA cognate to the last triplet of the minigene, thereby limiting
      protein synthesis for lack of the tRNA in question. We find that induction of a
      minigene ending in AUA stimulates bypassing at an AUA codon, but not in a control
      sequence with AGA at the test position; induction of a minigene ending in AGA
      stimulates bypassing at the latter but not the former. Induction of the AUA
      minigene also stimulates both leftward and rightward frameshifting at 'shifty'
      sequences containing an AUA codon. The normal, background frequency of bypassing
      at an AUA codon is markedly reduced by increasing the cellular level of the tRNA
      which reads the codon. Thus, the frequency of bypassing can be increased or
      decreased by lowering or raising the concentration of a relevant tRNA
      isoacceptor. These observations suggest that the occurrence of ribosome bypassing
      reflects the length of the pause at a given codon.

PMID- 12787355
TI  - Identification of Candida albicans genes induced during thrush offers insight
      into pathogenesis.
AB  - Candida albicans causes a wide spectrum of diseases, ranging from mucocutaneous
      infections like oral thrush to disseminated candidiasis. Screening for C.
      albicans genes expressed within infected hosts might advance understanding of
      candidal pathogenesis, but is impractical using existing techniques. In this
      study, we used an antibody-based strategy to identify C. albicans genes expressed
      during thrush. We adsorbed sera from HIV-infected patients with thrush against
      candidal cells grown in vitro and screened a C. albicans genomic expression
      library. We identified 10 genes encoding immunogenic antigens and used reverse
      transcription-polymerase chain reaction to verify that they were induced within
      thrush pseudomembranes recovered from a patient. The in vivo induced genes are
      involved in diverse functions, including regulation of yeast-hyphal
      morphogenesis, adhesion to host cells, nutrient uptake, phospholipid biosynthesis
      and amino acid catabolism. Four genes encode known virulence determinants (HWP1,
      CST20, CPP1 and RBF1). Another gene, LPD1, for which a role in candidal
      pathogenesis is unknown, encodes a protein homologous to a bacterial virulence
      determinant. Most importantly, disruption of CaNOT5, a newly identified gene,
      conferred defects in morphogenesis, decreased adherence to human buccal
      epithelial cells and attenuated mortality during murine disseminated candidiasis,
      proving that our strategy can identify genes encoding novel virulence
      determinants.

PMID- 12787356
TI  - Proteomic studies of diauxic lag in the differentiating prokaryote Streptomyces
      coelicolor reveal a regulatory network of stress-induced proteins and central
      metabolic enzymes.
AB  - Bacteria typically undergo intermittent periods of starvation and adaptation,
      emulated as diauxic growth in the laboratory. In association with growth arrest
      elicited by metabolic stress, the differentiating eubacterium Streptomyces
      coelicolor not only adapts its primary metabolism, but can also activate
      developmental programmes leading to morphogenesis and antibiotic biosynthesis.
      Here, we report combined proteomic and metabolomic data of S. coelicolor used to
      analyse global changes in gene expression during diauxic growth in a defined
      liquid medium. Cultures initially grew on glutamate, providing the nitrogen
      source and feeding carbon (as 2-oxoglutarate) into the TCA cycle, followed by a
      diauxic delay allowing reorientation of metabolism and a second round of growth
      supported by NH4+, formed during prediauxic phase, and maltose, a glycolytic
      substrate. Cultures finally entered stationary phase as a result of nitrogen
      starvation. These four physiological states had previously been defined
      statistically by their distinct patterns of protein synthesis and heat shock
      responses. Together, these data demonstrated that the rates of synthesis of heat
      shock proteins are determined not only by temperature increase but also by the
      patterns and rates of metabolic flux in certain pathways. Synthesis profiles for
      metabolic- and stress-induced proteins can now be interpreted by the
      identification of 204 spots (SWICZ database presented at
      http://proteom.biomed.cas.cz). Cluster analysis showed that the activity of
      central metabolic enzymes involved in glycolysis, the TCA cycle, starvation or
      proteolysis each displayed identifiable patterns of synthesis that logically
      underlie the metabolic state of the culture. Diauxic lag was accompanied by a
      structured regulatory programme involving the sequential activation of heat-,
      salt-, cold- and bacteriostatic antibiotic (pristinamycin I, PI)-induced
      stimulons. Although stress stimulons presumably provide protection during
      environmental- or starvation-induced stress, their identities did not reveal any
      coherent adaptive or developmental functions. These studies revealed interactive
      regulation of metabolic and stress response systems including some proteins known
      to support developmental programmes in S. coelicolor.

PMID- 12787357
TI  - The structure of the helically perturbed flagellar filament of Pseudomonas
      rhodos: implications for the absence of the outer domain in other complex
      flagellins and for the flexibility of the radial spokes.
AB  - Bacterial flagella, the organelles of motility, are commonly divided into two
      classes: 'plain' and 'complex'. The complex filaments are pairwise, helically
      perturbed forms of the plain filaments and have been reported to occur only in
      Rhizobium and Pseudomonas. Previously, we reconstructed and analysed the
      structure of the complex filaments of Rhizobium lupini H13-3 and determined their
      unique symmetry and origin of the perturbations (Trachtenberg et al., 1986, J Mol
      Biol 190: 569-576; 1987, 195: 603-620; 1998, 276: 759-773; Cohen-Krausz and
      Trachtenberg, 1998, J Struct Biol 122: 267-282). Here, we analyse the structure
      of the flagellar filament of the other known complex filament, that of
      Pseudomonas rhodos, as reconstructed from electron microscope images. Compared
      with the filament of R. lupini, the filament of P. rhodos is more flexible, as
      implied from high-intensity darkfield light microscopy and, although constructed
      from flagellins of higher molecular weights (59 versus 41 kDa), has similar
      symmetry. Using cryonegative stained specimens and low-dose, field emission
      electron microscopy, we reconstructed and averaged 158 filaments each containing
      170 statistically significant layer lines. The three-dimensional density maps of
      P. rhodos clearly suggest, when compared with those of R. lupini and the right
      handed Salmonella typhimurium SJW1655, that R. lupini is missing the outer
      flagellin domain (D3), that the interior of the complex filament is rather
      similar to that of the plain filament and that the radial spokes (connecting
      domains D0 and D1), present in individual density maps, average out because of
      their variability and implied flexibility. Extending the three-start grooves and
      ridges on the propeller's surface, in the form of an Archimedean screw, may
      further improve the motility of the cell in viscous environments.

PMID- 12787358
TI  - The DNA excision repair system of the highly radioresistant bacterium Deinococcus
      radiodurans is facilitated by the pentose phosphate pathway.
AB  - Deinococcus radiodurans is highly resistant to radiation and mutagenic chemicals.
      Mutants defective in the putative glucose-6-phosphate dehydrogenase gene (zwf-)
      and the aldolase gene (fda-) were generated by homologous recombination. These
      mutants were used to test the cells' resistance to agents that cause dimer
      formation and DNA strand breaks. The zwf - mutants were more sensitive to agents
      that induce DNA excision repair, such as UV irradiation and H2O2, but were as
      resistant to DNA strand break-causing agents such as methylmethanesulphonic acid
      (MMS) and mitomycin C (MMC) as the wild-type cells. Analysis of the cytoplasmic
      fraction of zwf- cells showed that the concentrations of inosine monophosphate
      (IMP) and uridine monophosphate (UMP) were only 30% of those found in the wild
      type cells. The fda- mutants were slightly more resistant to UV light and H2O2.
      Results suggested that the deinococcal pentose phosphate pathway augmented the
      DNA excision repair system by providing cells with adequate metabolites for the
      DNA mismatch repair.

PMID- 12787359
TI  - Opposing selective forces for expression of the gonococcal lactoferrin receptor.
AB  - All isolates of Neisseria gonorrhoeae express receptors that bind human
      transferrin (Tf). Although lactoferrin (Lf) is abundant on mucosa and in purulent
      exudates, many gonococci do not express an Lf receptor. The naturally occurring
      Lf receptor deletion mutant FA1090 (LbpB-LbpA-) is infectious, but a Tf receptor
      mutant of FA1090 is unable to infect male volunteers [Cornelissen, C.N., Kelley,
      M., Hobbs, M.M., Anderson, J.E., Cannon, J.G., Cohen, M.S., and Sparling, P.F.
      (1998) Mol Microbiol 27: 611-616]. Here, we report that expression of an Lf
      receptor in the absence of the Tf receptor was sufficient for infection, and that
      expression of both Lf and Tf receptors resulted in a competitive advantage over a
      strain that made only the Tf receptor in mixed infection of male volunteers. We
      confirmed that nearly 50% of clinical isolates do not make an Lf receptor.
      Surprisingly, about half of geographically diverse Lf - isolates representing
      many different auxotypes and porin serovars carried an identical lbpB lbpA
      deletion. Among Lf+ strains, all produced the integral outer membrane protein
      LbpA, but 70% did not express the lipoprotein LbpB. Thus, there are apparently
      selective pressures for expression of the Lf receptor in the male urethra that
      are balanced by others against expression of the Lf receptor in niches other than
      the male urethra.

PMID- 12787360
TI  - A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific
      transcript pattern.
AB  - The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane
      protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a
      variety of host receptors, are thought to be important virulence factors. The
      predominant expression of a single cytoadherent PfEMP1 type on an infected red
      blood cell, and the switching between different PfEMP1 types to evade host
      protective antibody responses, are processes thought to be controlled at the
      transcriptional level. Contradictory data have been published on the timing of
      var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR)
      data suggested that transcription of the predominant var gene occurs in the later
      (pigmented trophozoite) stages, whereas Northern blot data indicated such
      transcripts only in early (ring) stages. We investigated this discrepancy by
      Northern blot, with probes covering a diverse var gene repertoire. We confirm
      that almost all var transcript types were detected only in ring stages. However,
      one type, the well-conserved varCSA transcript, was present constitutively in
      different laboratory parasites and does not appear to undergo antigenic
      variation. Although varCSA has been shown to encode a chondroitin sulphate A
      (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts
      does not correlate with the CSA-binding phenotype.

PMID- 12787361
TI  - Oligomerization and activation of the FliI ATPase central to bacterial flagellum
      assembly.
AB  - FliI is the peripheral membrane ATPase pivotal to the type III protein export
      mechanism underlying the assembly of the bacterial flagellum. Gel filtration and
      multiangle light scattering showed that purified soluble native FliI protein was
      in a monomeric state but, in the presence of ATP, FliI showed a propensity to
      oligomerize. Electron microscopy revealed that FliI assembles to a ring
      structure, the yield of which was increased by the presence of a non-hydrolysable
      ATP analogue. Single particle analysis of the resulting electron micrograph
      images, to which no symmetry was applied, showed that the FliI ring structure has
      sixfold symmetry and an external diameter of approximately 10 nm. The oligomeric
      ring has a central cavity of 2.5-3.0 nm, which is comparable to the known
      diameter of the flagellar export channel into which export substrates feed.
      Enzymatic activity of the FliI ATPase showed positive co-operativity,
      establishing that oligomerization and enzyme activity are coupled. Escherichia
      coli phospholipids increased enzyme co-operativity, and in vitro cross-linking
      demonstrated that they promoted FliI multimerization. The data reveal central
      facets of the structure and action of the flagellar assembly ATPase and, by
      extension, the homologous ATPases of virulence-related type III export systems.

PMID- 12787362
TI  - The use of flow cytometry to detect expression of subunits encoded by 11
      Salmonella enterica serotype Typhimurium fimbrial operons.
AB  - The Salmonella enterica serotype Typhimurium (S. Typhimurium) genome contains 13
      putative fimbrial operons termed agf (csg), fim, pef, lpf, bcf, saf, stb, stc,
      std, stf, sth, sti and stj. Evidence for in vitro expression of fimbrial proteins
      encoded by these operons is currently only available for agf, fim and pef. We
      raised antisera against putative major fimbrial subunits of S. Typhimurium,
      including AgfA, FimA, PefA, LpfA, BcfA, StbA, StcA, StdA, StfA, SthA and StiA.
      Elaboration of StcA on the bacterial surface could be detected by flow cytometry
      and immunoelectron microscopy after expression of the cloned stcABCD operon from
      a heterologous T7 promoter in Escherichia coli. To study the expression of
      fimbrial antigens in S. Typhimurium by flow cytometry, we constructed strains
      carrying deletions of agfAB, pefBACDI, lpfABCDE, bcfABCDEFG, stbABCD, stcABC,
      stdAB, stfACDEFG, sthABCDE or stiABCDE. Using these deletion mutants for gating,
      expression of fimbrial antigens was measured by flow cytometry in cultures grown
      in vitro or in samples recovered 8 h after infection of bovine ligated ileal
      loops with S. Typhimurium. FimA was the only fimbrial antigen expressed by S.
      Typhimurium after static growth in Luria-Bertani (LB) broth. Injection of static
      LB broth cultures of S. Typhimurium into bovine ligated ileal loops resulted in
      the expression of BcfA, FimA, LpfA, PefA, StbA, StcA, StdA, StfA and StiA. These
      data show that in vivo growth conditions drastically alter the repertoire of
      fimbrial antigens expressed in S. Typhimurium.

PMID- 12787364
TI  - RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes,
      which are rescued by tmRNA.
AB  - RelE of Escherichia coli is a global inhibitor of translation that is activated
      by nutritional stress. Activation of RelE depends on Lon-mediated degradation of
      RelB, the antagonist that neutralizes RelE. In vitro, RelE cleaves synthetic
      mRNAs positioned at the ribosomal A-site. We show here that in vivo
      overexpression of RelE confers cleavage of mRNA and tmRNA in their coding
      regions. RelE-mediated cleavage depended on translation of the RNAs and occurred
      at both sense and stop codons. RelE cleavage of mRNA and tmRNA was also induced
      by amino acid starvation. An ssrA deletion strain was hypersensitive to RelE,
      whereas overproduction of tmRNA counteracted RelE toxicity. After neutralization
      of RelE by RelB, rapid recovery of translation required tmRNA, indicating that
      tmRNA alleviated RelE toxicity by rescuing ribosomes stalled on damaged mRNAs.
      RelE proteins from Gram-positive Bacteria and Archaea cleaved tmRNA with a
      pattern similar to that of E. coli RelE, suggesting that the function and target
      of RelE may be conserved across the prokaryotic domains.

PMID- 12787365
TI  - Three-way interactions among the Sfh, StpA and H-NS nucleoid-structuring proteins
      of Shigella flexneri 2a strain 2457T.
AB  - Shigella flexneri 2a strain 2457T has been found to express Sfh, a new member of
      the H-NS-like family of nucleoid-structuring proteins. With H-NS and its
      paralogue, StpA, this brings to three the number of these proteins expressed in
      this bacterium. This raises the possibility that three-way interactions may occur
      in S. flexneri among these proteins and between the proteins and each other's
      genes. Such three-way interactions among H-NS-like proteins have not been
      described previously. The expression of the sfh, stpA and hns genes was studied
      at the transcriptional and post-transcriptional levels. The Sfh protein displays
      growth phase-dependent regulation that distinguishes it from both H-NS and StpA.
      Like H-NS and StpA, Sfh can bind to its own promoter region, it negatively
      autoregulates transcription of its own gene, and when overexpressed all three
      proteins cross-repress transcription of each other's genes. The presence of
      highly conserved oligomerization domains within these molecules suggested the
      possibility of protein-protein interactions. Like H-NS and StpA, the purified Sfh
      protein forms homodimers in solution. Using the yeast two-hybrid assay we show
      that each of the three proteins also forms homodimers in vivo and, additionally,
      each protein can form heterodimers with either of its homologues. This raises the
      possibility that Sfh may modulate the activities of H-NS and StpA, and vice
      versa.

PMID- 12787363
TI  - The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response
      to antifungal drugs and loss of calcineurin function.
AB  - Cell wall integrity is crucial for fungal growth, development and stress
      survival. In the model yeast Saccharomyces cerevisiae, the cell integrity
      Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and
      promote cell wall remodelling under stress conditions. We have identified the
      Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and
      have characterized its role in the maintenance of cell integrity in response to
      elevated growth temperature and in the presence of cell wall synthesis
      inhibitors. C. neoformans Mpk1 is required for growth at 37 degrees C in vitro,
      and this growth defect is suppressed by osmotic stabilization. C. neoformans
      mutants lacking Mpk1 are attenuated for virulence in the mouse model of
      cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations
      of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase
      inhibitor), caspofungin (a beta-1,3-glucan synthase inhibitor), or FK506 (a
      calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to
      nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play
      complementing roles in regulating cell integrity in C. neoformans. Our studies
      demonstrate that pharmacological inhibition of the cell integrity pathway would
      enhance the activity of antifungal drugs that target the cell wall.

PMID- 12787366
TI  - Surface localized glyceraldehyde-3-phosphate dehydrogenase of Mycoplasma
      genitalium binds mucin.
AB  - Mycoplasma genitalium is the smallest known self-replicating cell. It was first
      isolated from urethral specimens in individuals with non-gonococcal urethritis
      and, more recently, from respiratory and synovial sites. Our laboratory has been
      interested in defining the mechanisms by which M. genitalium adheres to and
      colonizes host cell surfaces. In order to determine potential targets of
      adherence, we examined the interaction of M. genitalium with a primary component
      of the mucosal epithelial lining, mucin (Mn). Three Mn-binding proteins (MnBPs)
      of M. genitalium were isolated by affinity chromatography. One of these proteins
      was identified by N-terminal sequencing as glyceraldehyde-3-phosphate dehy
      drogenase (GAPDH). Antiserum raised against recombinant GAPDH blocked binding of
      intact biosynthetically labelled mycoplasmas to mucin by approximately 70%. Whole
      cell radioimmunoprecipitation indicated that GAPDH was surface-accessible and
      surface localization of GAPDH was further verified by membrane fractionation and
      immunoelectron microscopy. The role of GAPDH as an adhesin to Mn not only
      provides insights into the organism's mechanisms of adherence and colonization
      but also into its ability to maximize its limited genome.

PMID- 12787370
TI  - Great scots!

PMID- 12787371
TI  - Introduction of night shift call system for surgical trainees: a prospective self
      controlled trial.
AB  - OBJECTIVE: The number of hours worked by specialty trainees has come under
      scrutiny recently. One approach aimed at decreasing the number of consecutive
      hours worked is the night shift call system (NSCS). This study aimed to determine
      the advantages and disadvantages of an NSCS compared with those of the
      conventional overnight call system (ONCS). SUBJECTS AND METHODS: Sixteen basic
      surgical trainees (BSTs) from our unit participated in this prospective, self
      controlled trial. During April 2000, the conventional 1-in-4 ONCS with a post
      call half-day off was instituted. From May to June 2000, each BST rotated to work
      1 week of night duty (20.00-08.00) and 7 weeks of daytime duty. A battery of
      neuropsychological tests were administered to the group after call during the
      study period. RESULTS: On average the numbers of consecutive hours worked during
      the NSCS and ONCS periods were 12 and 28 hours, respectively. There was no
      difference in numbers of errors committed and no difference in discrepancy
      between diagnoses made on admission and discharge. Two of the simple
      neuropsychological tests (memory scanning and addition tests) showed a
      significant fall-off in performance during the ONCS period (P < 0.05). Most
      specialists preferred the ONCS, while the majority of the BSTs preferred the NSCS
      (P < 0.05). This was because without extra manpower, the overall workloads of
      senior staff were increased. CONCLUSIONS: The NSCS is 1 way of reducing work
      hours, and was associated with significantly less impaired cognition on the part
      of our BSTs. It is only feasible if extra relieving staff are available to cover
      daytime duties.

PMID- 12787372
TI  - A web-based presentation of an undergraduate clinical skills curriculum.
AB  - AIMS: The aim of this study was to use information and communications technology
      to present a curriculum of clinical skills in a user-friendly format. SETTING: A
      UK undergraduate medical school with a problem-based curriculum and a strong
      emphasis on proficiency in clinical skills. STUDY DESIGN: Case study describing
      the qualitative analysis of users' requirements and development of a web-based
      learning portfolio. EVALUATION: The study involved direct observation of users
      during a 'think-aloud' protocol, a validated software users' measurement
      inventory and a 17-item questionnaire designed to test whether 'SkillsBase' met
      its users' requirements. RESULTS: Students wanted a clear and flexible
      presentation of their skills curriculum that was easy to navigate, offered
      instructional material and standards for self- and peer assessment, offered
      useful Internet links, allowed them to compare their progress with school
      standards and peer norms, and could be used as a learning portfolio. During the
      think-aloud protocol, students made very few errors in data interpretation or
      navigation, and found SkillsBase easy to learn and aesthetically pleasing to use.
      They rated it higher on all measures of usability than standard commercial
      software. The questionnaire showed that it met most aspects of its design
      specification, although many students were doubtful that they would use its
      reflective function. It is available for inspection at
      http://www.skillsbase.man.ac.uk/. CONCLUSIONS: SkillsBase meets the design
      specification for a training and reflective aid to learning clinical skills and
      is very usable.

PMID- 12787373
TI  - Health professionals' sex and attitudes of health science students to health
      claims.
AB  - INTRODUCTION: The huge influx of women into medicine may modify discriminatory
      attitudes towards health professionals. The aim of this study was to confirm the
      possible influence of health professionals' biological sex on the perception of
      the suitableness of health claims and on the attribution of responsibility in the
      case of presumed malpractice. METHODS: A total of 448 health science students,
      123 of whom were male and 325 of whom were female, made up the sample. They
      represented 63% of students enrolled on their courses. They were asked to read a
      story about a fictitious event that results in a health claim. The story had 2
      versions that differed only in the genders of the professionals involved. The
      students had to answer a 5-point Likert scale questionnaire with 12 items, 7 of
      which referred to the pertinence of the claim, 2 to the responsibility of the
      medical staff, 1 to the responsibility of the nursing staff, 1 to the
      responsibility of the health authority and 1 to the responsibility of the
      hospital where the incident occurred. Each student judged only 1 of the 2
      possible versions, which were randomly distributed. Almost all the students
      invited to collaborate did so. Group differences were assessed by 2-way anova
      analysis. RESULTS: Significantly more responsibility was assigned to the male
      nurse than to the female nurse. Male students, but not female students,
      considered the claim more valid in version B. CONCLUSION: These results show
      that, at least amongst our sample of health science students, negative prejudices
      towards female professionals do not exist.

PMID- 12787374
TI  - Communication skill of general practitioners: any room for improvement? How much
      can it be improved?
AB  - OBJECTIVE: To measure any changes in the communication skills of primary care
      physicians before and after a part-time Diploma course in Family Medicine.
      SUBJECTS: 79 Hong Kong Chinese doctors (46 of whom were local graduates, with an
      average of 7 years in general practice). METHODS: Over the 10-month course in
      2000-01, participants had 11 2.5-hour lecture/demonstrations in communication
      skills, 2 sessions of role play practice in groups of 20, self-analysis of a
      videotaped interview and skills evaluation. A before-after design measured scores
      in videotaped simulated patient interviews (rated by a research assistant using a
      structured observation guide, after standardisation by a psychologist) and scores
      in Objective Structured Clinical Examinations (OSCE) (rated by experienced family
      physician examiners with standardised checklists). RESULTS: There were wide
      variations in baseline skills, with scores ranging between 24-78 (out of 100) for
      video and 18-68 for OSCE, which were related to prior training and inversely
      associated with years after graduation. Significant improvements occurred in both
      video (from 53 to 61) and OSCE (from 46 to 56) post-course (P < 0.001). The group
      in the lowest quartile improved from 36 to 54 for video and from 29 to 48 for
      OSCE, while those in the second lowest quartile improved from 50 to 61 for video
      and from 44 to 56 for OSCE (F = 12.2, P < 0.001). Doctors who graduated more than
      20 years ago made as much improvement as more recent graduates. CONCLUSIONS:
      Communication skills can be effectively taught to, and improved among experienced
      Chinese doctors by a combination of large-class teaching and medium-sized group
      practice with feedback, and without intensive individual supervision.

PMID- 12787375
TI  - The effect of three commercial coaching courses on Step One USMLE performance.
AB  - BACKGROUND: A substantial industry exists to provide formal review courses for
      Step 1 of the United States Medical Licensing Examination (USMLE). There are
      limited data on the usefulness of these courses. AIM: To determine whether or not
      student participation in a commercial coaching course improves performance on
      Step 1 of the USMLE. METHODS: Scores achieved by 468 students on the National
      Board of Medical Examiners (NBME) Comprehensive Basic Science Examination (CBSE)
      were used to predict a score on Step 1 of the USMLE. The NBME is the organisation
      that prepares and administers the USMLE. Predicted USMLE scores were then
      regressed against the actual scores achieved by the students on Step 1. The
      students were divided into 2 groups: those who took a 3-4-week live commercial
      coaching course and those who studied on their own. RESULTS: The regression lines
      for the 369 students who studied on their own and the 99 students who took a
      commercial coaching course were statistically indistinguishable. The analysis was
      powerful enough to have picked up a difference of 1% on average (P = 0.05) or 2
      questions out of the 350 constituting Step 1 of the USMLE. Neither the students
      who performed above average nor those who performed below average on the CBSE
      improved their performance on Step 1 as a result of the coaching courses.
      CONCLUSIONS: Students who take a live, 3-4-week commercial coaching course to
      improve performance on Step 1 of the USMLE do not achieve higher scores than
      students who study on their own. Students should strongly consider whether or not
      a substantial investment in time and money for a commercial coaching course is
      justified in the light of such meagre returns.

PMID- 12787376
TI  - Participating in medical education: views of patients and carers living in
      deprived communities.
AB  - OBJECTIVES: Active patient involvement in community-based education is still
      relatively novel; in particular, the involvement of patients living in socially
      and economically deprived areas is still unusual. This study explores the views
      of patients and carers living in deprived areas on their participation in medical
      education. DESIGN: A total of 36 patients and 18 parents were interviewed at home
      by Year 1 students undertaking an accelerated 4-year degree programme.
      Subsequently, taped interviews using a topic guide were carried out with 18
      patients/carers. Their views on their active involvement with medical students
      are presented here. RESULTS: Most of the patients in this study did not view
      themselves as teaching the students but considered their role to be more one of
      partnership, explanation and sharing. They considered that they were the 'best
      judges' of certain aspects of their illness. These aspects related to
      psychological, social and behavioural issues, which impacted on both themselves
      and their families. Patients considered these issues to be as important as the
      medical condition they were diagnosed with. Patients also raised issues
      concerning the importance of doctors listening to patients. CONCLUSION: This
      study showed that patients living in areas of deprivation were positive about
      being involved in medical education. They considered their personal experience
      and knowledge of illness to be an important aspect of student learning. They were
      happy to share this knowledge and they were very keen that doctors should listen
      to them. The challenge for medical educators is to ensure that this is achieved.

PMID- 12787377
TI  - Peer assessment of competence.
AB  - OBJECTIVE: This instalment in the series on professional assessment summarises
      how peers are used in the evaluation process and whether their judgements are
      reliable and valid. METHOD: The nature of the judgements peers can make, the
      aspects of competence they can assess and the factors limiting the quality of the
      results are described with reference to the literature. The steps in
      implementation are also provided. RESULTS: Peers are asked to make judgements
      about structured tasks or to provide their global impressions of colleagues.
      Judgements are gathered on whether certain actions were performed, the quality of
      those actions and/or their suitability for a particular purpose. Peers are used
      to assess virtually all aspects of professional competence, including technical
      and non-technical aspects of proficiency. Factors influencing the quality of
      those assessments are reliability, relationships, stakes and equivalence.
      CONCLUSION: Given the broad range of ways peer evaluators can be used and the
      sizeable number of competencies they can be asked to judge, generalisations are
      difficult to derive and this form of assessment can be good or bad depending on
      how it is carried out.

PMID- 12787378
TI  - Making sense of clinical reasoning: judgement and the evidence of the senses.
AB  - BACKGROUND: Close noticing, as keen discrimination and judgement between
      qualities, is a key capability for work in visual domains in medicine. This
      generic capability is normally assumed, and its specifics are left to develop
      through experience, as traditional apprenticeship in a specialty. Discrimination
      is an outcome of learning in the affective domain, and introduces a vital
      aesthetic dimension to clinical work that aligns with the interests of the
      medical humanities. An aesthetic approach to clinical reasoning, however, remains
      largely unexplored as an explicit focus for medical education. FRAMEWORK AND
      PRACTICE PARADOXES: We offer a framework for an explicit education of perceptual
      discrimination in the visual domain as a form of practice 'artistry', turning a
      surface 'looking' into a deeper 'seeing'. Such an education, however, raises
      certain paradoxes. While novices typically 'see' what they expect to see in
      visual images (sign and symptom), experts also make similar errors. Further,
      experts become familiar with the use of visual heuristics in diagnosis, such as
      vivid natural referents to aid in rapid pattern recognition in an encompassing
      diagnostic 'glance', yet this appears to defeat the first principle of describing
      what you see. Employing a model of imagination as a tacit form of knowing that
      'prepares' and enhances perception, we suggest, however, that the judicious use
      of such heuristics can be positive. Moreover, the mechanics of the process of
      clinical judgement in visual domains can be detailed to inform educational
      agendas. A further paradox is that of experts using both idiosyncratic heuristics
      and protocol-driven practices, where these seem to offer contradictory approaches
      to gaining knowledge. We recognise this as a facet of medicine's inherent
      uncertainty, in the face of complex, ambiguous and unique material, that must be
      addressed through clinical education. CONCLUSION: We equate 'aesthetics' with
      'sensibility' and describe clinical expertise as 'connoisseurship' of
      informational images. Such connoisseurship, a particular form of knowing, can, in
      turn, be defined as an aesthetic sensibility informing practice artistry. It can
      be articulated and analysed to provide a basis for educational enhancement.
      Connoisseurship is not a technical-rational procedure but is inherently
      paradoxical and such paradox may be valued as an educational resource, rather
      than seen as a hindrance.

PMID- 12787379
TI  - The Arts in Medicine: setting up and evaluating a new special study module at
      Leicester Warwick Medical School.
AB  - CONTEXT: A special study module (SSM) option was introduced for medical students
      at Leicester Warwick Medical School in January 2000. Its aim was to enhance
      students' knowledge and understanding of people's experiences and emotions in
      relation to health and sickness through study of the arts. The module was set up
      and run through collaboration between the medical school and the University of
      Leicester's Department of English. This paper describes the context of SSMs in
      the arts and their relevance to medicine, and examines student perceptions of the
      benefits gained from this particular course. METHOD: Students were exposed to a
      core series of arts-based seminars, and were given time to research a chosen
      study topic looking at an artist or art form in relation to health and sickness
      issue(s). They were assessed on their written submissions on these study topics
      according to the module objectives. Students were encouraged to develop a
      reflective style of learning by keeping learning journals. CONCLUSIONS:
      Evaluation demonstrated that the students considered that their professional
      development had been enhanced by taking time to study the arts. Students also
      felt that they would continue to use the arts to this end after the module had
      finished. Summative assessment showed that the objectives were achievable by the
      great majority of students.

PMID- 12787380
TI  - The Art of Medicine through the Humanities: an overview of a one-month humanities
      elective for fourth year students.
AB  - BACKGROUND: The purpose of incorporating humanities teaching into medical
      education is to encourage students to develop into more sensitive and caring
      doctors who communicate well with their patients and colleagues. CONTENT: A
      unique 4th year student elective at the Medical College of Wisconsin incorporates
      reflective and writing activities. Small group sessions are facilitated by
      faculty with specific interest and expertise in the humanities. EVALUATION:
      Students keep a journal in which they record their reflections on personal
      issues, career planning and reactions to classroom discussions. Each student
      writes a poem and an essay or short story. The course is well received and
      oversubscribed. CONCLUSIONS: Students increase their understanding of the
      humanities through readings, small group discussions, journal keeping and formal
      writing. By incorporating humanism into their professional lives, medical
      students can learn to care for their patients in a more humane and thoughtful
      manner.

PMID- 12787381
TI  - HIV/AIDS in the visual arts: applying discipline-based art education (DBAE) to
      medical humanities.
AB  - CONTEXT AND RATIONALE: Health professions educators have been systematically
      attempting to insert the humanities into health professions curricula for over 4
      decades, with various degrees of success. Among the several medical humanities,
      the visual arts seem particularly adequate for the teaching/learning of crucial
      aspects of medicine. Educational efforts in the arts require, however, a sound
      pedagogical philosophy of art education. Health professions educators need
      therefore to be aware of educational frameworks in the arts. Discipline-based art
      education (DBAE) is a recognised contemporary educational framework for the
      teaching/learning of the arts, which may be adapted to medical humanities.
      OBJECTIVE: It is the ultimate objective of this essay to share the experience of
      applying this educational framework to a course in a medical curriculum. METHODS:
      The author describes a course on the representations of HIV/AIDS in the visual
      arts, with explicit reference to its objectives, content, instructional features
      and student assessment in the light of DBAE, whose principles and characteristics
      are described in detail. RESULTS AND CONCLUSION: Discipline-based art education
      may be applied to medical humanities courses in a medical curriculum. This essay
      throws light on how this structure may be particularly useful for designing other
      pedagogically sound art courses in health professions curricula.

PMID- 12787382
TI  - The views of paediatric specialist registrars on the annual record of in-training
      assessments.

PMID- 12787383
TI  - Allocation of training posts in Austria.

PMID- 12787384
TI  - Self-assessment scores and gender.

PMID- 12787389
TI  - Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus
      mutations.
AB  - BACKGROUND: We previously reported three aquaporin-2 (AQP2) gene mutations known
      to cause autosomal-dominant nephrogenic diabetes insipidus (NDI) (Am J Hum Genet
      69:738, 2001). The mutations were found in the C-terminus of AQP2 (721delG, 763
      to 772del, and 812 to 818del). The wild-type AQP2 is a 271 amino acid protein,
      whereas these mutant genes were predicted to encode 330 to 333 amino acid
      proteins due to the frameshift mutations leading to the creation of a new stop
      codon 180 nucleotides downstream. The Xenopus oocyte expression study suggested
      that the trafficking of the mutant AQP2s was impaired. METHODS: To determine the
      cellular pathogenesis of these NDI-causing mutations in mammalian epithelial
      cells, Madin-Darby canine kidney (MDCK) cells were stably transfected with the
      wild-type AQP2, or the 763 to 772del mutant AQP2, or both. Cells were grown on
      the membrane support to examine the localization of AQP2 proteins by
      immunofluorescence microscopy. RESULTS: Confocal immunofluorescence microscopy
      showed that the wild-type AQP2 was expressed in the apical region, whereas the
      mutant AQP2 was apparently located at the basolateral region. Furthermore, the
      wild-type and mutant AQP2s were colocalized at the basolateral region when they
      were cotransfected, suggesting the formation of mixed oligomers and thereby
      mistargeting. CONCLUSION: Mixed oligomers of the wild-type and the 763 to 772del
      mutant AQP2s are mistargeted to the basolateral membrane due to the dominant
      negative effect of the mutant. This defect is very likely to explain the
      pathogenesis of autosomal-dominant NDI. The mistargeting of the apical membrane
      protein to the basolateral membrane is a novel molecular pathogenesis of
      congenital NDI.

PMID- 12787390
TI  - Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop
      codon mutation Stop78Arg.
AB  - Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop
      codon mutation Stop78Arg. BACKGROUND: Mutations in the gene for apolipoprotein
      AII (apoAII) have recently been found to cause hereditary renal amyloidosis. In
      each case amyloid deposition has been associated with a peptide extension at the
      carboxyl-terminus of apoAII, the result of mutations in the normal stop codon.
      METHODS: A Caucasian man who has had progressive renal dysfunction since age of
      34 was found to have amyloidosis on renal biopsy at age 56. Echocardiogram showed
      mild intraventricular septal thickness and technetium-99m (99mTc)-pyrophosphate
      scintigraphy demonstrated uptake by cardiac muscle consistent with amyloid
      deposition in the myocardium. His father died of renal failure and his paternal
      half brother has renal dysfunction. RESULTS: DNA sequencing of the apoAII gene in
      the proband showed a T to C transition at the first position of the stop codon
      indicating replacement of the stop codon by l-arginine (Arg) at residue 78.
      Western analysis of the proband's plasma under reducing conditions using anti
      apoAII revealed an extra band at approximately 10 kD in addition to the normal
      apoAII band at 8 kD. Western analysis of solubilized amyloid fibrils isolated
      from rectal biopsy tissue contained only the variant apoAII. CONCLUSION: These
      results indicate that the proband's amyloid fibrils are derived from apoAII and
      the amyloidogenesis is linked to the peptide extension at the carboxyl-terminus
      of variant apoAII. Of particular interest is that this novel apoAII variant may
      cause amyloid cardiomyopathy in addition to renal amyloid.

PMID- 12787391
TI  - Steroid-resistant nephrotic syndrome and congenital anomalies of kidneys:
      evidence of locus on chromosome 13q.
AB  - BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) and congenital anomalies
      of kidney and urinary tract (CAKUT) are major causes of renal dysfunction in
      children. Although a few patients with 13q deletion have been previously reported
      with renal anomalies, the association of SRNS with 13q has not been reported and
      critical regions associated with CAKUT have not been identified. We present the
      results of deletion mapping studies to identify the critical regions. METHODS:
      Cytogenetic and deletion mapping studies were performed on DNA obtained from
      peripheral blood of two children with renal anomalies and interstitial deletion
      of 13q as well as their parents. Twenty eight microsatellite markers with a
      spacing of 1-8 Mb (1-3 cM) were utilized. RESULTS: The patients (both males, 5
      and 10 years old) had varying severity of developmental delay and other
      neurologic disorders. The renal involvement included hydronephrosis, ureterocele,
      renal dysplasia, and mesangioproliferative SRNS. Our studies imply existence of
      at least two critical regions in the 13q area that are linked to CAKUT. The first
      is a 7 Mb region defined by markers D13S776 and D13S891 shared by both patients.
      The second is a much larger region extending at least 33 Mb above D13S776 seen in
      one patient with severe renal malformations and SRNS. CONCLUSION: We report an
      association of chromosome 13q with CAKUT as well as SRNS. Our studies suggest the
      presence of more than one gene in this region that is likely to be involved in
      renal development and function.

PMID- 12787392
TI  - Altered expression of immune modulator and structural genes in neonatal
      unilateral ureteral obstruction.
AB  - BACKGROUND: Congenital obstructive nephropathy is a condition characterized by
      hydronephrosis, tubular dilatation, apoptosis, and atrophy, as well as
      interstitial cellular infiltration and progressive interstitial fibrosis. The
      renal consequences of chronic unilateral ureteral obstruction (UUO) in the
      neonatal rat are similar to those of clinical congenital obstructive nephropathy.
      METHODS: To define alterations in renal gene expression induced by chronic
      neonatal UUO, Sprague-Dawley rats were subjected to UUO or sham operation within
      the first 2 days of life, and kidneys were harvested after 12 days. RESULTS:
      Microarray analysis revealed that the mRNA expression of multiple immune
      modulators, including krox24, interferon-gamma regulating factor-1 (IRF-1),
      monocyte chemoattractant protein-1 (MCP-1), interleukin-1beta (IL-1beta),
      CCAAT/enhancer binding protein (C/EBP), p21, c-fos, c-jun, and pJunB, was
      significantly increased in obstructed compared to sham-operated kidneys (all P <
      0.05). Western blot analysis revealed significant changes in immune modulator
      protein abundance in the obstructed versus sham-operated kidney for krox24 (P =
      0.0004), IRF-1 (P = 0.005), MCP-1 (P = 0.01), and JunD (P = 0.0008).
      Alternatively, the abundance of all of the immune modulator proteins was similar
      in sham-operated and obstructed kidneys in rats subjected to acute (4 days)
      neonatal UUO. Microarray analysis studies also reveal that structural genes that
      comprise the cytoskeleton and cell matrix are significantly up-regulated by
      chronic neonatal UUO, including calponin, desmin, dynamin, and lumican (all P <
      0.05). CONCLUSION: Multiple genes are aberrantly expressed in the kidney of rats
      subjected to chronic neonatal UUO. Elucidation of these genes involved in
      neonatal UUO may lead to new insight about congenital obstructive nephropathy.

PMID- 12787393
TI  - Clinical characterization of a family with a mutation in the uromodulin (Tamm
      Horsfall glycoprotein) gene.
AB  - BACKGROUND: We have recently identified a mutation in the uromodulin gene in a
      large family affected with hyperuricemia, gout, and renal failure. The purpose of
      this investigation is to provide a comprehensive characterization of the clinical
      findings of this syndrome in family members who had a mutation in the uromodulin
      gene. METHODS: An extended family suffering from hyperuricemia and gout was
      identified by a local practitioner. After consent was obtained, patients provided
      a directed clinical history and blood and urine specimens for chemical and
      genetic testing. All family members were tested for the presence of uromodulin
      gene mutations by direct DNA sequence analysis. The clinical and biochemical
      characteristics of family members carrying the affected mutation were then
      investigated. RESULTS: Thirty-nine family members were found to have an exon 5
      uromodulin gene mutation (g.1966 1922 del), and 29 unaffected family members were
      identified. The cardinal clinical features in individuals with the uromodulin
      mutation included hyperuricemia, decreased fractional excretion of uric acid, and
      chronic interstitial renal disease leading to end-stage renal disease (ESRD) in
      the fifth through seventh decade. Women did not always develop hyperuricemia or
      gout, but still developed progressive chronic renal failure. CONCLUSION: Mutation
      of the uromodulin gene resulted in hyperuricemia, reduced fractional excretion of
      uric acid, and renal failure. Genetic testing will be required to definitively
      identify individuals suffering from this condition. We are interested in studying
      other families that may suffer from this condition and would appreciate any such
      referrals.

PMID- 12787394
TI  - Detection of inflammation following renal ischemia by magnetic resonance imaging.
AB  - BACKGROUND: Determining the disease culprits in human acute renal failure (ARF)
      has been difficult because of the paucity of renal biopsies and the lack of
      noninvasive methods to determine the location or cause of renal injury. Recently,
      ultrasmall superparamagnetic iron oxide (USPIO) particles have been used to
      detect inflammation in animal models. Therefore, we tested if USPIO enhanced
      magnetic resonance imaging (MRI) could detect inflammation in ischemic ARF in
      rats. METHODS: Rats were subjected to 40 or 60 minutes of bilateral ischemia or
      injected with mercuric chloride. MR images were obtained before and 24 hours
      after USPIO injection, and the signal intensity decrease in the outer medulla was
      measured. Cells containing iron particles were identified by iron staining and
      transmission electron microscopy (TEM). Leukocytes were identified by ED-1 and
      chloracetate esterase staining. RESULTS: Injection of USPIO particles caused a
      black band to appear in the outer medulla at 48, 72, and 120 hours after
      ischemia. This band was not detected in normal animals, 24 hours after ischemia,
      or 48 hours after mercuric chloride injection. The signal intensity change in the
      outer medulla correlated with serum creatinine and the number of iron particle
      containing cells. Most infiltrating cells were macrophages, and iron particles
      were present inside lysosomes of macrophages. USPIO injection did not alter renal
      function in normal or ischemic animals. CONCLUSION: USPIO-enhanced MRI could
      detect inflammation noninvasively from 48 hours after 40 or 60 minutes of renal
      ischemia in rats. This method might be useful to understand the pathogenesis of
      human ARF and to evaluate the effectiveness of anti-inflammatory agents.

PMID- 12787395
TI  - PPARgamma ligand attenuates PDGF-induced mesangial cell proliferation: role of
      MAP kinase.
AB  - BACKGROUND: Mesangial proliferation is a key feature in the pathogenesis of a
      number of renal diseases and can be experimentally induced by the mitogen
      platelet-derived growth factor (PDGF). Mitogen-activated protein kinase (MAPK)
      signaling plays a key role in mesangial cell proliferation. In the present study
      we examined whether peroxisome proliferator-activated receptor gamma (PPARgamma)
      activators/ligands, thiazolidinediones such as ciglitazone, troglitazone, and
      rosiglitazone, can inhibit cell proliferation by modulating individual steps in
      the MAPK pathway. METHODS: Mouse mesangial cells were made quiescent and
      proliferation was measured following the application of PDGF. Using ciglitazone
      as the model compound, the mechanism of the antiproliferative effect of PPARgamma
      activators on MAPK and specific cell cycle regulatory proteins were examined by
      Western blot analysis and transfection studies. RESULTS: Ciglitazone inhibited
      PDGF-induced mesangial cell proliferation in a dose-dependent manner (1 to 20
      micromol/L). The inhibitory effect was blocked by a peroxisome proliferator
      activated receptor element (PPRE) decoy oligonucleotide, indicating that the
      observed effect of ciglitazone was via PPARgamma activation. Ciglitazone (1 to 20
      micromol/L) did not affect extracellular signal-regulated protein kinase (ERK)
      activation but inhibited the activation of serum response element (SRE) by 85 +/-
      6% (P < 0.01). This effect was associated with a reduction in c-fos expression
      (80 +/- 9%, P < 0.01). Ciglitazone (1, 10, and 20 micromol/L) also inhibited
      cyclin D1 expression by 37 +/- 8%, 79 +/- 15%, and 87 +/- 12%, respectively (P <
      0.001 to 0.001), and p21 expression by 45 +/- 6% (P < 0.01), 61 +/- 10% (P <
      0.001), and 72 +/- 8% (P < 0.001), respectively. Ciglitazone inhibited PDGF
      mediated up-regulation of p27. In addition, the antiproliferative effect of
      ciglitazone was potentiated by PD98059, a mitogen-activated protein (MAP) kinase
      kinase (MEK) inhibitor that acts at a step upstream from ERK. CONCLUSION: These
      data indicate that PPARgamma activation may inhibit mesangial growth directly by
      affecting MAPK and cell cycle regulatory proteins. Furthermore, a MAP kinase
      inhibitor can potentiate the antiproliferative effect.

PMID- 12787396
TI  - Autoregulation in the parathyroid glands by PTH/PTHrP receptor ligands in normal
      and uremic rats.
AB  - BACKGROUND: The secretion of parathyroid hormone (PTH) from the parathyroid
      glands might be regulated by autocrine/paracrine factors. We have previously
      shown that N-terminal parathyroid hormone-related protein (PTHrP) enhanced the
      secretory PTH response to low calcium in vivo and in vitro in rat parathyroid
      glands. N-terminal PTHrP fragments are equipotent to N-terminal PTH as ligands
      for the PTH/PTHrP receptor that is demonstrated in parathyroid tissue. This
      supports the possibility that the parathyroid cells respond to PTH/PTHrP receptor
      ligands and as such are target for an autoregulatory action of PTH and PTHrP. Our
      aim was to search for the PTH/PTHrP receptor in rat parathyroid glands and to
      examine the effects of PTHrP 1-40 on PTH secretion in in vivo models of secondary
      hyperparathyroidism (HPT) in uremic rats. METHODS: PTH secretion was examined
      during ethyleneglycol tetraacetic acid (EGTA)-induced hypocalcemia both with and
      without PTHrP. Five groups, each of six normal rats, received a bolus of
      increasing doses of 0.1, 1.0, 10, and 100 microg of PTHrP 1-40, or vehicle only.
      Chronic renal failure (CRF) was induced by 5/6 nephrectomy. One group of 12 CRF
      rats received a standard diet, while another CRF group of 18 rats received a high
      phosphorus diet to induce more severe HPT. After 8 weeks of uremia, the rats were
      infused with EGTA and PTHrP 1-40 or vehicle. The presence of the PTH/PTHrP
      receptor in the rat parathyroid glands was examined by reverse transcription
      polymerase chain reaction (RT-PCR) technique. PTH was measured by a rat PTH assay
      that does not cross-react with PTHrP. RESULTS: In a dose-related manner, PTHrP
      enhanced the PTH response to hypocalcemia in normal rats. A similar rate of
      decrease of plasma Ca++ was induced by EGTA in all experimental groups. In CRF
      rats, plasma creatinine (0.99 +/- 0.10 mmol/L vs. 0.33 +/- 0.01 mmol/L, P <
      0.001) and plasma PTH (226 +/- 32 pg/mL vs. 69 +/- 16 pg/mL, P < 0.001) levels
      were significantly increased. The CRF rats on high phosphorus diet had
      significant hypocalcemia (Ca++, 1.04 +/- 0.02 mmol/L vs. 1.28 +/- 0.03 mmol/L, P
      < 0.001), hyperphosphatemia (3.48 +/- 0.3 mmol/L vs. 2.25 +/- 0.1 mmol/L, P <
      0.001) and severe secondary HPT, PTH (984 +/- 52 pg/mL vs. 226 +/- 32 pg/mL, P <
      0.001) compared to CRF rats on a standard phosphorus diet. The maximal PTH
      response to hypocalcemia was enhanced in CRF rats (maximum PTH 382 +/- 58 pg/mL
      vs. 196 +/- 29 pg/mL in normal rats, P < 0.01) and further enhanced by PTHrP 1-40
      to 826 +/- 184 pg/mL (P < 0.01). The secretory capacity of the parathyroid glands
      in response to low Ca++ was severely diminished in uremia. In CRF rats given a
      high phosphorus diet, the basal PTH levels were at the upper part of the
      calcium/PTH curve, and the induction of more marked hypocalcemia did not
      stimulate PTH secretion further (maximum PTH 1475 +/- 208 pg/mL vs. basal 1097 +/
      69 pg/mL, NS). PTHrP, however, further enhanced the maximal PTH levels
      significantly (maximum PTH 3142 +/- 296 pg/mL, P < 0.01). The presence of the
      PTH/PTHrP receptor in the rat parathyroid glands was confirmed by RT-PCR
      technique. CONCLUSION: PTHrP enhanced significantly, in a dose-related manner,
      the low Ca++-stimulated PTH secretion in normal rats. The PTH/PTHrP receptor is
      present in rat parathyroid glands. The impaired secretory capacity of the
      parathyroid glands in uremic rats is significantly enhanced by PTHrP. An
      autocrine/paracrine role in the parathyroid glands of the PTH/PTHrP receptor
      targeting peptides, PTHrP and PTH, is suggested. Thus, it is hypothesized that
      PTH during hypocalcemia might have a positive auto-feedback regulatory role on
      its own secretion.

PMID- 12787397
TI  - Angiotensin II-induced hypertrophy of proximal tubular cells requires p27Kip1.
AB  - BACKGROUND: Angiotensin II (Ang II), as a single factor, induces hypertrophy of
      cultured proximal tubular cells of various species. Cells undergoing hypertrophy
      are arrested in the G1 phase of the cell cycle. Ang II also stimulated the
      expression of p27Kip1, an inhibitor of cyclin-dependent kinases (CDK). Although
      previous studies inhibiting p27Kip1 expression with antisense oligonucleotides
      suggested that this CDK inhibitor is important for Ang II-induced hypertrophy of
      proximal tubular cells, nonspecific effects of antisense technology, and the
      inability to transfect 100% of cells raised concerns about the true role of
      p27Kip1 in tubular hypertrophy. METHODS: Proximal tubular cells were isolated and
      cultured from wild-type (p27Kip1+/+) and knockout (p27Kip1-/-) mice. p27Kip1
      genomic and protein expression was evaluated. Proximal tubular cell origin was
      confirmed by expression of various markers [3M-1 antigen, gamma
      glutamyltransferase, angiotensin-converting enzyme (ACE)]. Cell proliferation
      (cell number, 3[H]thymidine incorporation) and hypertrophy (de novo protein
      synthesis as measured by 3[H]leucine incorporation, hypertrophy index, cell size)
      were evaluated. CDK2 and CDK4 activities were determined by an in vitro kinase
      assay. In addition, cell cycle analysis was performed by flow cytometry. p27Kip1
      expression was reconstituted in two different clones of p27Kip1-/- proximal
      tubular cells using an inducible vector system based on ecdysone response
      elements. RESULTS: In accordance with previous studies, 10-7 mol/L Ang II induces
      hypertrophy and cell cycle arrest of p27Kip1+/+ proximal tubular cells. In
      contrast, Ang II facilitated cell cycle progression of two p27Kip1-/- proximal
      tubular cell lines without inducing hypertrophy. Ang II activates CDK4/cyclin D
      kinase activity in p27Kip1+/+ and -/- tubular cells, but stimulates CDK2/cyclin E
      activity only in wild-type cells. However, in the presence of Ang II,
      reconstituting p27Kip1 expression in p27Kip1-/- tubular cells using an inducible
      expression system, restored G1 phase arrest and the hypertrophic phenotype. Ang
      II did not induce apoptosis of either p27Kip1+/+ or -/- tubular cells.
      CONCLUSION: Our findings are the first clear evidence that p27Kip1 is required
      for Ang II-induced hypertrophy of proximal tubular cells. However, although
      p27Kip1 expression is an absolute requirement for this hypertrophy,
      reconstitution experiments revealed that other factors induced by Ang II
      contribute to this hypertrophy.

PMID- 12787398
TI  - AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a
      potential target for N-acetylcysteine treatment in dialysis patients.
AB  - AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A
      potential target forN-acetylcysteine treatment in dialysis patients. BACKGROUND:
      Oxidative stress largely contributes to hemodialysis-associated lethal
      complications, thus explaining the urgent need of antioxidant-based therapeutic
      strategies in hemodialysis patients. We previously identified advanced oxidation
      protein products (AOPP) in the uremic plasma as exquisite markers of oxidative
      stress and potent mediators of monocyte activation. The present study was aimed
      at searching whether (1) AOPP can also trigger activation of polymorphonuclear
      neutrophils (PMN), and (2) whether AOPP-induced activation could be inhibited by
      N-acetylcysteine (NAC), a widely used compound which has been shown to prevent
      oxidative injury to kidney. METHODS: Both human serum albumin (HAS) AOPP (i.e.,
      HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of
      hemodialysis patients) were tested for their capacity to trigger phagocyte
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase
      (MPO)-dependent activities as measured by lucigenin- and luminol-amplified
      chemiluminescence (CL), respectively, as compared to receptor-dependent
      [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The
      effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC
      on normal monocyte and on normal or hemodialysis patient's (N = 16) PMN oxidative
      responses were compared. RESULTS: HSA-AOPP triggered in a HOCl dose-dependent
      manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further
      enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients
      also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP-mediated
      responses of normal monocyte and of normal and uremic PMN but had no significant
      effect on opsonized zymosan- or PMA-induced CL responses. CONCLUSION: This dual
      potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP
      without affecting those mediated by compounds mimicking pathogens supports the
      proposal of a therapeutic trial with NAC aimed at reducing oxidative stress
      related inflammation in hemodialysis patients.

PMID- 12787399
TI  - Blockade of TGF-beta action ameliorates renal dysfunction and histologic
      progression in anti-GBM nephritis.
AB  - BACKGROUND: We tested whether the entire soluble extracellular domain of the
      human transforming growth factor-beta (TGF-beta) type II receptor, fused to the
      Fc portion of human immunoglobulin G (IgG1) (Tbeta-ExR) and expressed in skeletal
      muscles by adenovirus-mediated gene transfer (AdTbeta-ExR), can ameliorate renal
      dysfunction and histologic progression in a rat experimental anti-glomerular
      basement membrane (GBM) nephritis. METHODS: Anti-GBM nephritis was induced in
      Wistar Kyoto rats by an intravenous injection of anti-rat glomerular basement
      membrane (GBM) sera. At day 1 (24 hours after induction), AdTbeta-ExR (1 x 109
      pfu/mL) was injected into the femoral muscle in the treatment group, and an
      adenovirus vector-expressing bacterial beta-galactosidase (AdLacZ) was injected
      into the control group. Then, clinical and histologic changes were examined for 3
      weeks after the induction of anti-GBM nephritis. RESULTS: Tbeta-ExR was detected
      in the serum at day 7, but the serum concentration of Tbeta-ExR had decreased
      below the detectable level by day 14. Although blood pressure and the degree of
      proteinuria were similar in both groups, the deterioration of renal function was
      significantly blunted in the treatment group. Crescent formation and interstitial
      fibrosis were also ameliorated in the treatment group. These histologic
      improvements were accompanied by the decreased interstitial infiltration of
      macrophages and the decreased alpha-smooth muscle actin (alpha-SMA)-positive
      cells in the glomeruli and the interstitium. CONCLUSION: This study demonstrated
      for the first time that the blockade of TGF-beta action by AdTbeta-ExR in the
      early stage of anti-GBM nephritis ameliorates the clinical and histologic
      progression. In addition, this study shed light on the development of a specific
      gene therapy for human crescentic glomerulonephritis.

PMID- 12787400
TI  - Gene delivery using human cord blood-derived CD34+cells into inflamed glomeruli
      in NOD/SCID mice.
AB  - BACKGROUND: Bone marrow reconstitution using genetically-modified hematopoietic
      stem cells has been reported to confer resistance to inflammation and prevent
      renal injury in glomerulonephritis. Although this strategy has potentials for
      clinical use, taking hematopoietic stem cells from bone marrow is highly
      stressful for patients. In this regard, umbilical cord blood may be a useful
      alternative and, therefore, we focused on their suitability as a source of
      hematopoietic stem cells for transplantation-based therapy for
      glomerulonephritis. METHODS: CD34+ cells were obtained from human umbilical cord
      blood, retrovirally transduced with human beta-glucuronidase (HBG) gene, and
      transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID)
      mice. After confirming the successful chimerism, these mice were treated with
      lipopolysaccharide (LPS), and local HBG expression in glomeruli was examined
      using immunohistochemical analysis, HBG bioassay, and Western blot analysis.
      RESULTS: Clonogenic assay showed that 88.4 +/- 5.9% burst-forming unit-erythroid
      (BFU-E), 79.7 +/- 11.4% in colony-forming unit-macrophage (CFU-M), and 81.1 +/-
      14.1% in colony-forming unit-granulocyte (CFU-G), respectively, possessed the
      transgene after transfection, suggesting that precommited cells were susceptible
      to retroviral infection. Flow cytometric analysis revealed that 24.1 +/- 14.5% of
      bone marrow cells in these chimera mice expressed human lymphocyte antigen (HLA)
      8 weeks after transplantation. Also, clonogenic assay showed that a sustained
      engraftment of human hematopoietic cells expressed HBG. CD14-positive cells were
      recruited into the glomeruli upon LPS treatment and they secreted bioactive HBG,
      suggesting that cord blood-derived CD34+cells may differentiate into monocyte
      lineage while maintaining the expression of the transgene. CONCLUSION: These data
      indicate that umbilical cord blood cells can be utilized as a source of
      hematopoietic stem cells for the transplantation-based therapy of
      glomerulonephritis.

PMID- 12787401
TI  - Laminin-8/9 is synthesized by rat glomerular mesangial cells and is required for
      PDGF-induced mesangial cell migration.
AB  - BACKGROUND: Laminin (LM), the major glycoprotein component of basement membranes
      is expressed as multiple isoforms in a developmentally regulated and tissue
      specific manner. LM alpha4 has a limited tissue distribution and is highly
      expressed in the developing glomerulus. In the present study, we investigate the
      in vivo and in vitro expression and function of LM alpha4 in the glomerulus.
      METHODS: LM alpha4 expression was examined by Northern blot, reverse
      transcription polymerase chain reaction (RT-PCR), Western blot, and
      immunofluorescence microscopy. Mesangial cells (MC) were plated on purified LM-1,
      LM-2, and LM-8/9. Immunofluorescence microscopy was performed to examine the
      cellular phenotypes induced by LM-1 and LM-8/9. A modified Boyden chamber method
      was used to assess laminin participation in platelet-derived growth factor (PDGF)
      stimulated migration. RESULTS: mRNA for LMalpha4 is expressed in cultured rat MC,
      and isolated rat and mouse glomeruli, but not in cultured rat glomerular
      epithelial cells or glomerular endothelial cells. Using antibodies specific for
      LM alpha4, a 240 kD band was detected in MC extract and a slightly smaller band
      was identified in extracted rat glomeruli. Purified LM-8/9 had MC adhesive
      activity comparable to LM-1 and LM-2. MC attached to LM-8/9 exhibited a unique
      phenotype. In contrast to LM-1, attachment of MC to LM-8/9 produced a highly
      arborized cell morphology with significantly reduced formation of focal contacts
      or stress fibers. LM alpha4 is utilized by MC during PDGF-stimulated migration.
      CONCLUSION: LM alpha4 is synthesized by MC and persists in the mature glomerulus.
      LM-8/9 stimulates a unique cellular morphology, and they are utilized in PDGF
      induced migration. These factors suggest that LM alpha4 plays an important role
      in MC differentiation and in the maintenance of MC phenotype.

PMID- 12787402
TI  - Role of alpha8 integrin in mesangial cell adhesion, migration, and proliferation.
AB  - BACKGROUND: Extracellular matrix receptors of the integrin family are known to
      regulate cell adhesion, migration, and proliferation. The alpha8 integrin chain
      is expressed in the glomerulus exclusively by mesangial cells. The contribution
      of alpha8 to mesangial cell function, however, has not yet been studied. METHODS:
      Mesangial cells from wild-type and alpha8-deficient mice were isolated and
      characterized. Integrin expression was assessed by real-time polymerase chain
      reaction (PCR), Western blot, or fluorescence-activated cell sorter (FACS)
      analysis. Cell adhesion was determined by conventional attachment assay and a
      centrifugal assay for cell adhesion. Cell migration was determined by a
      fluorescence-based transmigration assay and a chemotaxis assay. Proliferation
      rates were determined by BrdU and [3H]-thymidine assays. RESULTS: On the alpha8
      ligands fibronectin and vitronectin, but not on collagens, attachment of alpha8
      deficient mesangial cells was reduced compared to wild-type cells. In contrast,
      alpha8-deficient mesangial cells migrated more easily and displayed an increased
      proliferative response on fibronectin or vitronectin, but not on collagens,
      compared to wild-type cells. These effects were not due to an up-regulation of
      the fibronectin or vitronectin receptors alpha5 or alphav in alpha8-deficient
      mesangial cells, as the cell surface expression of integrins alpha5 and alphav
      was comparable in wild-type and alpha8-deficient mesangial cells. CONCLUSION:
      These findings confirm a role for alpha8 integrin in the regulation of the
      mesangial cell phenotype. alpha8 integrin seems to promote adhesion, but inhibit
      migration and proliferation of mesangial cells. Thus, the data support the
      hypothesis that alpha8 integrin could play an important role for maintaining
      tissue integrity in the glomerulus during glomerular injury.

PMID- 12787404
TI  - SCG/Kinjoh mice: a model of ANCA-associated crescentic glomerulonephritis with
      immune deposits.
AB  - BACKGROUND: Spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj)
      mice spontaneously develop crescentic glomerulonephritis (CGN), systemic
      vasculitis, and perinuclear ANCA (pANCA), and have been suggested as an animal
      model for human antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AASV). Since no systematic serologic, immunohistologic, or structural evaluation
      had been performed thus far, we reinvestigated the development of ANCA and CGN in
      these mice. METHODS: SCG/Kj mice were subjected to serologic and urinary
      analysis, as well as histologic evaluation of the kidneys by standard light,
      immunofluorescence, and electron microscopy at regular intervals during the
      course of the disease. RESULTS: Perinuclear ANCA developed as early as the 6th
      week of life, increasing both in frequency and titer in up to 100% of animals at
      week 20. Crescent formation began at week 10 and peaked at week 16, maximally
      affecting 57% of glomeruli. Crescent formation was initiated by "activated"
      podocytes that formed cell bridges between tuft and Bowman's capsule. The typical
      picture of a diffuse immune complex nephritis was found in all animals as early
      as 8 weeks. Fluorescence intensity increased with age and became strongly
      positive for immunoglobulin (Ig)A, IgM, IgG, and C3 in the mesangium and along
      the peripheral capillary loops. CONCLUSION: Although ANCAs were found in the
      majority of animals, the massive presence of glomerular immune deposits differed
      from the pauci-immune pattern found in human AASV, making this model not
      completely representative for human ANCA-associated CGN. However, the spontaneous
      and concomitant development of pANCA, small vessel vasculitis, and CGN raises the
      opportunity to analyze pathogenetic links between these disease manifestations in
      vivo.

PMID- 12787403
TI  - Radiographic contrast media-induced tubular injury: evaluation of oxidant stress
      and plasma membrane integrity.
AB  - BACKGROUND: Experimental and clinical investigations suggest that oxidant stress
      is a critical determinant of radiocontrast nephropathy (RCN), and that N acetyl
      cysteine (NAC) can prevent this damage. This study addresses these issues
      directly at the tubular cell level. Potential alternative mechanisms for RCN have
      also been sought. METHODS: Isolated mouse proximal tubule segments (PTS), or
      cultured proximal tubule (HK-2) cells, were subjected to radiocontrast media
      (RCM) (Ioversol, Optiray 320) exposure, followed by assessments of cellular
      viability [% lactate dehydrogenase (LDH) release, tetrazolium dye (MTT), uptake]
      and lipid peroxidation. These experiments were conducted in the absence or
      presence of a variety of antioxidants [NAC, glutathione (GSH), superoxide
      dismutase, catalase] or pro-oxidant (GSH depletion, heme oxygenase inhibition)
      strategies. RCM effects on mitochondrial and plasma membrane integrity were also
      assessed. RESULTS: RCM exposure did not induce PTS lipid peroxidation. Neither
      antioxidant nor pro-oxidant interventions mitigated or exacerbated RCM-induced
      tubular cell injury, respectively. RCM impaired mitochondrial integrity, as
      assessed by ouabain-resistant ATP reductions, and by cytochrome c release (before
      cell death). RCM also induced plasma membrane damage, as indicated by loss of key
      resident proteins (NaK-ATPase, caveolin) and by increased susceptibility to
      phospholipase A2 (PLA2) attack (increase of >/=2 times in free fatty acid and NaK
      ATPase release). Hyperosmolality could not account for RCM's toxic effects.
      CONCLUSION: RCM toxicity can be dissociated from tubular cell oxidant stress.
      Alternative mechanisms may include mitochondrial injury/cytochrome c release and
      plasma membrane damage. The latter results in critical protein loss, as well as a
      marked increase in plasma membrane susceptibility to exogenous/endogenous PLA2
      attack.

PMID- 12787405
TI  - Precocious activation of genes of the renin-angiotensin system and the fibrogenic
      cascade in IgA glomerulonephritis.
AB  - BACKGROUND: The renin-angiotensin system (RAS) seems to play a pivotal role in
      progression of immunoglobulin A (IgA) nephropathy (IgAN). Accordingly, in
      patients with IgAN a relationship between the RAS and the fibrogenic cascade
      triggered by transforming growth factor-beta1 (TGF-beta1) should be observed.
      This study was carried out to obtain deeper insight into the regulation of RAS
      and the interaction with TGF-beta1 in the diseased kidney. METHODS: Twenty renal
      biopsies from IgAN patients and five from renal cancer patients (controls) were
      analyzed in both microdissected glomerular and tubulointerstitial compartments by
      reverse transcription-polymerase chain reaction (RT-PCR). All patients had normal
      renal function. The expression of the following genes was determined:
      angiotensinogen (Agtg), renin, angiotensin-converting enzyme (ACE), angiotensin
      II (Ang II) type 1 and type II (AT1 and AT2 receptors), TGF-beta1, collagen IV
      (Coll IV), alpha-smooth muscle actin (alpha-SMA). Quantitative data were
      confirmed for TGF-beta1 and ACE genes by real-time PCR. Results. RAS genes were
      overexpressed in IgAN patients vs. control subjects. There was no difference
      between glomerular and tubulointerstitial RAS gene expression levels. On the
      contrary, the overactivation of fibrogenic cascade genes (TGF-beta1, Coll IV,
      alpha-SMA) in the tubulointerstitium was observed (TGF-beta1, glomerular 0.14 +/-
      0.10 SD; tubulointerstial 0.34 +/- 0.20; P = 0.000) (alpha-SMA, glomerular 0.08
      +/- 0.07; tubulointerstitial 0.35 +/- 0.19; P = 0.000) (Coll IV, glomerular 0.12
      +/- 0.11; tubulointerstitial 0.22 +/- 0.10; P = 0.03). This fibrogenic cascade
      seems to be triggered by RAS as indicated by statistically significant
      correlations between the expression of their respective genes. A direct
      relationship between the putative Ang II activity and the expression of AT
      receptor genes was found in the tubulointerstitium, whereas in the glomeruli this
      relationship was negative. In the interstitium, statistically significant
      positive relationships emerged between interstitial infiltrates and the gene
      expression of Agtg, AT1 receptor, Coll IV, and TGF-beta1. CONCLUSION: This study
      demonstrates that a tight regulation of the intrarenal RAS exists in IgAN and
      that it follows the general rules disclosed in animal models. Moreover, the RAS
      seems to be activated early in the diseased kidney and it appears that such
      activation drives inflammation and a parallel stimulation of the TGF-beta
      fibrogenic loop, particularly at the tubulointerstitial level.

PMID- 12787406
TI  - IL-18 translational inhibition restricts IFN-gamma expression in crescentic
      glomerulonephritis.
AB  - BACKGROUND: Interleukin-18 (IL-18), a potent inducer of interferon gamma (IFN
      gamma) production, is a cytokine involved in the cell-mediated immune response
      that is expressed during inflammatory and pathologic conditions. IFN-gamma plays
      a role in the development of some models of glomerulonephritis (GN); however, the
      role of IL-18 in the production of IFN-gamma during these pathologies has not
      been studied. METHODS: Rat IL-18 cDNA was isolated and the regulation of IL-18
      gene expression was studied. IFN-gamma and IL-18 expression were determined in
      anti-glomerular basement membrane (GBM) antibody (Ab)-induced GN. Recombinant
      active IL-18 (rIL-18) was used to further identify its effect on IFN-gamma
      production during this GN. Glomerular injury and levels of IFN-gamma were assayed
      in Wistar Kyoto (WKY) rats with anti-GBM GN in the presence or absence of rIL-18.
      RESULTS: Rat IL-18, similar to the mouse clone, requires processing by the IL
      1beta converting enzyme to become activated. A rat IL-18 5'-untranslated region
      (UTR) translational inhibitor was identified that strongly inhibited the
      synthesis of IL-18. This translational inhibitor with different lengths (180 and
      130 bp) was highly expressed during GN and correlated with minimal IFN-gamma mRNA
      expression. Injection of recombinant active IL-18 in WKY rats with anti-GBM GN
      was associated with an increase of glomerular IFN-gamma levels, proliferating
      cell nuclear antigen (PCNA)-ED1+ cells, and PCNA-CD8+ cells, with worsening of
      glomerular injury. CONCLUSION: These data suggest that the translational control
      of IL-18 expression by its 5'-UTR limits the production of IL-18, resulting in
      restricted expression of mRNA and protein IFN-gamma in this model of GN.
      Furthermore, it was suggested that possible IL-18/IFN-gamma induction of local
      proliferation of macrophages and CD8+ cells might be an important mechanism for
      amplifying CD8+-mediated macrophage-dependent GN.

PMID- 12787407
TI  - Expression of NOS1 and soluble guanylyl cyclase by human kidney epithelial cells:
      morphological evidence for an autocrine/paracrine action of nitric oxide.
AB  - BACKGROUND: Nitric oxide plays an important role in the kidney through effects on
      both renal hemodynamics and tubular functions. Tubular epithelial cells are thus
      a target for nitric oxide. However, as to whether tubular epithelial cells
      endogeneously produce nitric oxide under physiologic conditions in human kidney
      is currently unknown. The aim of the present study was to characterize and
      localize in situ the nitric oxide synthase (NOS) isoforms (NOS1, NOS2, and NOS3)
      expressed in human normal kidney, and soluble guanylyl cyclase, the well-known
      target for nitric oxide. METHODS: Five complementary experimental approaches were
      used: (1) detection of NOS reductase activity by nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase histochemistry, (2) immunolocalization
      of the NOS isoforms (NOS1, NOS2, NOS3), (3) immunoblot analysis, (4) quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) analysis of NOS mRNA,
      and (5) measurement of NOS activity as the conversion rate of l-[14C]-arginine to
      l-[14C]-citrulline. In addition, in situ detection of soluble guanylyl cyclase
      was assessed by immunohistochemistry. RESULTS: All these techniques led to
      consistent results showing that epithelial cells of most tubules along the human
      nephron exhibit functional NOS1, with a corticomedullary gradient observed both
      at the protein and mRNA levels. Moreover, epithelial cells expressing NOS1 also
      express soluble guanylyl cyclase, indicating that these cells possess the
      machinery for autocrine/paracrine effect of nitric oxide. CONCLUSION: The present
      study demonstrates that NOS1 is strongly expressed in most tubules of the human
      nephron and therefore invites to consider epithelial cells as one of the major
      source of nitric oxide in the human kidney under physiologic conditions.

PMID- 12787408
TI  - Bcl-xL overexpression protects from apoptosis induced by HMG-CoA reductase
      inhibitors in murine tubular cells.
AB  - BACKGROUND: Hyperplasia is attributed to enhanced tubular cell proliferation with
      unbalanced cell death. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors induce apoptosis in a variety of cell lines, including
      proximal tubular cells. However, the mechanisms by which statins induce apoptosis
      in tubular cells have not been fully addressed. METHODS: Apoptosis induced by
      simvastatin was measured in murine tubular cells with and without overexpressing
      Bcl-xL. Expression of genes implicated in cell death was studied by Northern and
      Western blot. RESULTS: The treatment of proliferating murine tubular cells (MCT)
      with simvastatin induced apoptosis in a time- and dose-dependent manner (0.1 to 1
      micromol/L). Apoptosis was correlated with Bcl-xL mRNA and protein down
      regulation. By contrast, the treatment with simvastatin did not modify the
      expression of the proapoptotic protein Bax. Simvastatin treatment was associated
      with cytochrome C release from the mitochondria to the cytosol. We also observed
      the presence of active caspase 9 and 3 during apoptosis induced by simvastatin.
      These effects were reversed by mevalonate, farnesylpyrophosphate (FPP), and
      geranylgeranylpyrophosphate (GGPP), suggesting the involvement of protein
      prenylation. Simvastatin appears to alter the balance between cell-life and death
      promoting genes, as reflected by the decreased Bcl-xL/Bax ratio. Supporting this
      hypothesis, overexpression of Bcl-xL reduced the amount of apoptosis induced by
      simvastatin by 80% when compared with control vector-expressing cells. The
      overexpression of Bcl-xL also prevented the activation of caspase 9 and 3.
      CONCLUSION: Our results indicate that down-regulation of Bcl-xL expression
      mediates apoptosis induced by statins in tubular cells. These results may be
      relevant to the treatment of disorders characterized by altered tubular
      proliferation.

PMID- 12787409
TI  - HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LCAT, ACAT, LDL receptor, and
      SRB-1 in hereditary analbuminemia.
AB  - BACKGROUND: Hereditary analbuminemia is associated with hypercholesterolemia,
      which has been shown to be primarily caused by increased extrahepatic production
      of cholesterol. Nagase rats with hereditary analbuminemia (NAR) have been used as
      a model to dissect the effect of primary hypoalbuminemia from that caused by
      proteinuria in nephrotic syndrome. The present study was undertaken to explore
      the effect of hereditary analbuminemia on protein expression of the key factors
      involved in cholesterol metabolism. METHODS: Hepatic tissue protein abundance of
      3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha
      hydroxylase (a rate-limiting enzyme in cholesterol catabolism), low density
      lipoprotein (LDL) receptor, high density lipoprotein (HDL) receptor (SRB-1), acyl
      coA cholesterol acyltransferase-2 (ACAT-2), and plasma concentration of lecithin
      cholesterol acyltransferase (LCAT), as well as HMG-CoA reductase, ACAT, and LCAT
      activities were determined in fasting male NAR and Sprague-Dawley control rats.
      RESULTS: The NAR group exhibited significant up-regulation of HMG-CoA reductase
      protein abundance but normal HMG-CoA reductase enzymatic activity. This was
      coupled with a significant up-regulation of cholesterol 7alpha-hydroxylase and a
      mild up-regulation of ACAT protein abundance and activity. However, hepatic LDL
      receptor and HDL receptor and plasma LCAT protein concentration and activity were
      normal in NAR. CONCLUSION: Hypercholesterolemia in NAR is associated with
      elevated hepatic HMG-CoA reductase protein abundance, but normal HMG-CoA
      reductase activity. These findings point to post-translational regulation of this
      enzyme and favor an extrahepatic origin of hypercholesterolemia in NAR. The
      observed up-regulation of cholesterol 7alpha-hydroxylase represents a
      compensatory response to the associated hypercholesterolemia. Unlike nephrotic
      syndrome, which causes severe LDL receptor, HDL receptor, and LCAT deficiencies,
      hereditary analbuminemia does not affect these proteins.

PMID- 12787410
TI  - Modulation of Ca2+-activated K+ channel in renal artery endothelium in situ by
      nitric oxide and reactive oxygen species.
AB  - BACKGROUND: Endothelium-derived nitric oxide and reactive oxygen species (ROS)
      have been proposed to regulate vascular tone by complex mechanisms, including the
      modulation of ion channel function. In endothelial function itself, activation of
      Ca2+-activated K+ channels (KCa) plays a crucial role by inducing
      hyperpolarization, which promotes membrane potential-driven Ca2+ influx and Ca2+
      dependent synthesis of vasodilatory factors. In the present study, we tested
      whether nitric oxide and ROS modulate endothelial KCa function. METHODS: By
      employing the patch-clamp technique in endothelium of porcine renal arteries in
      situ, we identified a large-conductance Ca2+-activated K+ channel (big K+
      channel, BKCa) with a conductance of 297 +/- 6 pS. RESULTS: Channel activity was
      strongly controlled by the membrane potential and the cytosolic Ca2+
      concentration (EC50 3.1 +/- 0.5 micromol/L Ca2+ at 0 mV). Channel activity was
      inhibited by Ba2+ and iberiotoxin. At submicromolar [Ca2+]i, nitric oxide induced
      a dose-dependent stimulation of BKCa activity with a 10-fold increase at the
      highest dose tested (1 micromol/L). A similar stimulation was achieved by the
      nitric oxide donors, sodium nitroprusside (SNP), and diethylamine nitric oxide
      complex (DEA-NO). In contrast, ROS and, in particular, hydrogen peroxide (H2O2)
      led to dose-dependent inactivation of BKCa with an IC50 of 80 +/- 6 nmol/L and
      1.1 +/- 0.4 micromol/L, respectively. In isolated porcine renal arteries,
      bradykinin-induced vasodilation was significantly reduced by either iberiotoxin
      or H2O2. CONCLUSION: Direct stimulation of endothelial BKCa by nitric oxide might
      represent a novel mechanism of autocrine regulation of endothelial function and
      points to a positive feedback mechanism by promoting hyperpolarization and nitric
      oxide production itself. The ROS-induced inhibition of BKCa could be part of the
      cellular mechanisms by which ROS impairs endothelium-dependent vasodilation.

PMID- 12787411
TI  - Mass transfer of calcium across the peritoneum at three different peritoneal
      dialysis fluid Ca2+ and glucose concentrations.
AB  - BACKGROUND: In peritoneal dialysis, the rate of ultrafiltration has been
      predicted to be a major determinant of peritoneal calcium (Ca2+) removal. Hence,
      dialysis fluid glucose concentration should be an important factor governing the
      transperitoneal Ca2+ balance. The aim of this study was to test the effect of
      various dialysate glucose levels and selected dialysate Ca2+ levels on Ca2+
      removal in peritoneal dialysis patients. METHODS: Patients (N = 8) received,
      during a 7-week period, 2 L of lactate (30 mmol/L)/bicarbonate (10 mmol/L)
      buffered peritoneal dialysis solutions containing either 1.5% glucose and 1.0
      mmol/L Ca2+ or 2.5% glucose and 1.6 mmol/L Ca2+, or 4% glucose and 2.5 mmol/L
      Ca2+, respectively, provided in a three-compartment bag (trio system). Patients
      underwent standardized (4-hour) dwells, one for each of the three dialysates to
      assess permeability-surface area product (PS) or mass transfer area coefficients
      (MTAC) for ionized and "freely diffusible" Ca2+, lactate, glucose, bicarbonate,
      phosphate, creatinine, and urea. RESULTS: There was a clear-cut dependence of
      peritoneal Ca2+ removal on the rate of ultrafiltration. For large peritoneal to
      dialysate Ca2+ gradients (2.5 mmol/L Ca2+ in 4% glucose) a close fit of measured
      to simulated data was predicted by the three-pore model using nonelectrolyte
      equations. For low transperitoneal Ca2+ concentration gradients, however,
      directly measured Ca2+ data agreed with the simulated ones only when the
      peritoneal Ca2+ PS was set lower than predicted from pore theory (6 mL/min).
      CONCLUSION: There was a marked ultrafiltration dependence of transperitoneal Ca2+
      transport. Nonelectrolyte equations could be used to simulate peritoneal ion
      (Ca2+) transport provided that the transperitoneal ion concentration gradients
      were large. Based on our data 1.38 mmol/L Ca2+ in the dialysis fluid would have
      created zero net Ca2+ gain during a 4-hour dwell for 1.5% glucose, whereas 1.7
      and 2.2 mmol/L Ca2+ would have been needed to produce zero Ca2+ gain for 2.5%
      glucose and 3.9% glucose, respectively.

PMID- 12787412
TI  - L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of
      ischemic acute renal failure in rats.
AB  - BACKGROUND: In ischemic acute renal failure (ARF), nitric oxide-dependent
      regulation of renal hemodynamics and glomerular function is disturbed. Previous
      studies indicate that the nitric oxide precursor l-arginine (l-Arg) has
      beneficial effects on renal function. Here we further analyzed the impact of l
      Arg on functional and biochemical parameters of nitric oxide signaling during the
      course of ischemic ARF. METHODS: Ischemic ARF was induced in rats by bilateral
      clamping of renal arteries for 45 minutes. l-Arg was applied intraperitoneally
      during clamping, and orally during 14 days of follow-up. Glomerular filtration
      rate (GFR) and renal plasma flow (RPF) were measured, and biochemical parameters
      analyzed by protein immunoblots. RESULTS: Clamping resulted in 70% to 90%
      reduction of GFR and RPF, with a gradual recovery by day 14. Using an in situ
      assay with the oxidative fluorescent dye hydroethidine, increased tubular
      generation of O2- was detected in the early course of ischemic ARF, indicating
      enhanced oxidative stress. These findings were accompanied by up-regulation of
      the nitric oxide receptor, soluble guanylate cyclase, and by significant
      regulatory changes of inducible nitric oxide synthase (iNOS) and endothelial NOS
      expression. l-Arg had a beneficial effect on GFR and RPF, decreased O2-
      production, diminished up-regulation of soluble guanylate cyclase, and prevented
      up-regulation of iNOS. CONCLUSION: Ischemic ARF is accompanied by marked
      alterations in the expression of key enzymes of the nitric oxide pathway,
      indicative for deficiency of constitutive NOS activity. l-Arg supplementation
      reduces O2- generation and significantly improves the expression of nitric oxide
      signaling proteins as well as the recovery phase of ischemic ARF.

PMID- 12787413
TI  - Hypoxanthine plus xanthine oxidase causes profound natriuresis without affecting
      renal blood flow autoregulation.
AB  - BACKGROUND: Enhanced superoxide (O2-.) production by xanthine oxidase in
      ischemia/reperfusion has been implicated in structural damage. The reperfusion
      phase is accompanied by decreased tubular sodium reabsorption, which has been
      partly attributed to enhanced action of O2-. In the present study we assessed
      whether intrarenal increases of O2-. accomplished by concomitant intrarenal
      hypoxanthine and intravenous xanthine oxidase (HX/XO) infusion would decrease or
      increase sodium excretion, and whether HX/XO infusion could be responsible for
      the diminished efficacy of renal blood flow (RBF) autoregulation in
      ischemia/reperfusion. METHODS: In the first group of Sprague-Dawley rats, renal
      sodium handling was measured before and during O2-. infusion. In the second
      group, renal hemodynamics and RBF autoregulation were assessed. RESULTS:
      Intrarenal O2-. infusion dramatically increased urine flow from 14.5 +/- 2.0
      microL/min to 46.3 +/- 4.4 microL/min, urinary excretion of sodium (UNaV) from
      1.7 +/- 0.4 micromol/min to 8.6 +/- 0.9 micromol/min, and fractional excretion of
      sodium FENa from 1.2 +/- 0.4% to 7.6 +/- 1.2%. Urinary excretion of
      thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation,
      increased during HX/XO infusion. These changes were completely reversible.
      Glomerular filtration rate (GFR) decreased from 1.12 +/- 0.08 during baseline to
      0.79 +/- 0.06 during HX/XO (P < 0.05) and tended to increase toward baseline
      during recovery (0.84 +/- 0.06 mL/min/g kidney weight). HX/XO did not
      significantly affect mean arterial pressure (MAP). HX/XO decreased RBF in the
      second group from 8.4 +/- 0.6 mL/min/g kidney weight to 7.4 +/- 0.5 mL/min/g
      kidney weight (P < 0.05) and renal vascular resistance (RVR) slightly increased
      from 13.8 +/- 0.9 units under baseline conditions to 15.1 +/- 1.1 units during
      HX/XO infusion (P < 0.05). HX/XO did not significantly affect RBF autoregulation.
      Proteinuria and glucosuria were absent and light microscopy revealed no renal
      morphologic changes. CONCLUSION: Intrarenal O2-. infusion (1) dramatically
      increased sodium and volume excretion and (2) did not affect autoregulation of
      RBF. Thus, superoxide can markedly affect glomerulotubular balance by diverging
      actions on renal hemodynamics and reabsorptive function and could mediate the
      functional tubular consequences of ischemia/reperfusion.

PMID- 12787414
TI  - Association of decreased quality of life and erectile dysfunction in hemodialysis
      patients.
AB  - BACKGROUND: Quality of life in hemodialysis patients has been associated with
      treatment outcomes. We explored the impact of erectile dysfunction on quality of
      life in a cohort of hemodialysis subjects. METHODS: A random sample of 302
      Philadelphia area hemodialysis (HD) subjects was enrolled using a cross-sectional
      design. Subjects completed a self-administered questionnaire including items on
      sexual function, past medical history, and quality of life. Linear regression
      (accounting for sampling design by weighted estimation methods) was used to
      examine the associations between various measures of quality of life (the
      dependent variables) and erectile dysfunction (ED) and other variables (the
      predictor variables). RESULTS: We found the emotional domains of the SF-36, a
      multi-purpose, short-form health survey with 36 questions, to be more profoundly
      associated with ED than the physical domains. Using the physical and mental
      components of the SF-12, a new 12-item short form health survey as predictors of
      ED, only the mental composite score (MCS) was statistically significant after
      adjusting for age and diabetes (P = 0.008). Subjects with ED had significantly
      lower quality of life mean scores. In particular, ED was associated with poorer
      social interaction (mean score difference, -10.3, adjusted P < 0.001), decreased
      emotional well-being (-12.9, adjusted P = 0.005), more role limitations due to
      emotional problems (-22.9, adjusted P = 0.01), and poorer social function (-17.8,
      P = 0.001). CONCLUSION: Recent advances in therapies for ED warrant that the
      diagnosis and treatment of erectile dysfunction be included in the global health
      assessment by the nephrologists and primary care providers of patients with renal
      insufficiency, as it may improve the quality of life of patients.

PMID- 12787415
TI  - Renal dysfunction and serious infections after open-heart surgery.
AB  - BACKGROUND: Infections and sepsis are important determinants of mortality in
      patients with renal dysfunction. We studied the influence of preoperative renal
      function or postoperative acute renal failure (ARF) on the frequency of
      infections after open-heart surgery. METHODS: This was a retrospective analysis
      of 24,660 patients undergoing open-heart surgery from 1993 to 2000. Primary
      outcome was occurrence of serious infections after open-heart surgery; secondary
      outcome was hospital mortality. RESULTS: Overall incidence of infections after
      open-heart surgery was 3.3%. The infection rate was higher in patients with lower
      preoperative creatinine clearance, ranging between 2.2% and 10.0%. Regarding
      postoperative ARF, the frequency of infections was 58.5% in those patients
      requiring dialysis vs. 23.7% in those with ARF not requiring dialysis (P <
      0.001); within each subgroup, however, the infection rates were similar
      regardless of the baseline renal function. In patients who did not develop ARF by
      either of our definitions, the infection rate was 1.6%. By multivariate analysis,
      preoperative renal function was an independent risk factor associated with
      infections [odds ratio (OR) for preoperative creatinine>1.2 mg/dL, 1.3; CI, 1.1
      to 1.6]. The relationship between preoperative renal function and infection
      prevailed even after excluding the patients with postoperative ARF. The overall
      morality was 2.2%; the mortality in patients with serious infection was 31.7%.
      CONCLUSION: Both preoperative renal dysfunction and postoperative ARF influence
      the frequency of serious infections after open-heart surgery. The infection rate
      was higher in patients with postoperative ARF regardless of the baseline renal
      function. However, preoperative renal dysfunction portended higher risk of
      infection, independent of the influence of postoperative ARF.

PMID- 12787416
TI  - Renal cell carcinoma as a cause of end-stage renal disease in the United States:
      patient characteristics and survival.
AB  - BACKGROUND: The patient characteristics and mortality associated with renal cell
      carcinoma (RCC) as a cause of end-stage renal disease (ESRD) have not been
      characterized for a national population. METHODS: An historical cohort study of
      renal cell carcinoma (RCC) was conducted from April 1, 1995, to December 31,
      1999. Included were 360,651 patients in the United States Renal Data System
      (USRDS) who were initiated on ESRD therapy with valid causes of ESRD. RESULTS: Of
      the study population, 1646 patients (0.5%) had RCC. The mean age of patients with
      RCC was 66.8 +/- 14.6 years versus 61.3 +/- 16.4 years for patients with other
      causes of ESRD (P < 0.01 by Student t test). The unadjusted 3-year survival
      (censored at the date of renal transplantation) of patients with RCC during the
      study period was 23% versus 36% in all other patients [adjusted hazard ratio
      (AHR), 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.019 by Cox
      regression]. However, patients with RCC who underwent nephrectomy (bilateral or
      unilateral) had significantly better survival compared to RCC patients who did
      not (AHR, 0.73, 95% CI, 0.63-0.85, P < 0.01), and their survival was not
      significantly different in comparison with nondiabetic ESRD patients. Bilateral
      nephrectomy (vs. unilateral) was not associated with any difference in adjusted
      mortality. CONCLUSION: Among patients with ESRD, the demographics of those with
      RCC were similar to those of patients with RCC in the general population.
      Overall, patients with RCC had decreased survival compared to patients with other
      causes of ESRD; those who underwent nephrectomy had significantly better survival
      than those who did not, with survival comparable to patients with nondiabetic
      ESRD.

PMID- 12787417
TI  - Nonadherence in hemodialysis: associations with mortality, hospitalization, and
      practice patterns in the DOPPS.
AB  - BACKGROUND: Nonadherence among hemodialysis patients compromises dialysis
      delivery, which could influence patient morbidity and mortality. The Dialysis
      Outcomes and Practice Patterns Study (DOPPS) provides a unique opportunity to
      review this problem and its determinants on a global level. METHODS: Nonadherence
      was studied using data from the DOPPS, an international, observational,
      prospective hemodialysis study. Patients were considered nonadherent if they
      skipped one or more sessions per month, shortened one or more sessions by more
      than 10 minutes per month, had a serum potassium level openface>6.0 mEq/L, a
      serum phosphate level openface>7.5 mg/dL (>2.4 mmol/L), or interdialytic weight
      gain (IDWG)>5.7% of body weight. Predictors of nonadherence were identified using
      logistic regression. Survival analysis used the Cox proportional hazards model
      adjusting for case-mix. RESULTS: Skipping treatment was associated with increased
      mortality [relative risk (RR) = 1.30, P = 0.01], as were excessive IDWG (RR =
      1.12, P = 0.047) and high phosphate levels (RR = 1.17, P = 0.001). Skipping also
      was associated with increased hospitalization (RR = 1.13, P = 0.04), as were high
      phosphate levels (RR = 1.07, P = 0.05). Larger facility size (per 10 patients)
      was associated with higher odds ratios (OR) of skipping (OR = 1.03, P = 0.06),
      shortening (OR = 1.03, P = 0.05), and IDWG (OR = 1.02, P = 0.07). An increased
      percentage of highly trained staff hours was associated with lower OR of skipping
      (OR = 0.84 per 10%, P = 0.02); presence of a dietitian was associated with lower
      OR of excessive IDWG (OR = 0.75, P = 0.08). CONCLUSION: Nonadherence was
      associated with increased mortality risk (skipping treatment, excessive IDWG, and
      high phosphate) and with hospitalization risk (skipping, high phosphate). Certain
      patient/facility characteristics also were associated with nonadherence.

PMID- 12787418
TI  - Coronary artery, aortic wall, and valvular calcification in nondialyzed
      individuals with type 2 diabetes and renal disease.
AB  - BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent
      and severe vascular and valvular calcification. We undertook this study to test
      the hypothesis that vascular and valvular calcification begins and is often
      severe long before diabetic renal disease progresses to ESRD. METHODS: A total of
      32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal
      disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate
      (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of
      18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic
      controls without renal disease, matched for age, gender, ethnicity, and the
      presence/absence of dyslipidemia, hypertension, and known coronary artery disease
      (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of
      coronary artery calcification was significantly greater among diabetic renal
      disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs.
      10, P < 0.001) than the nondiabetic controls. The coronary artery calcification
      scores were significantly more severe among diabetic renal disease individuals
      than either the diabetic or nondiabetic controls. Among individuals with diabetic
      renal disease, the coronary artery calcification and aortic wall calcification
      scores were several-fold greater among those with known CAD than among those
      without. There was also a significantly greater prevalence of aortic and mitral
      valve calcification among diabetic renal disease individuals than nondiabetic
      controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001).
      Multivariate analysis using all three groups reproduced these findings and also
      consistently identified age and diabetic renal disease as additional predictors
      for the presence or severity of coronary artery and aortic wall calcification.
      CONCLUSION: In this first, systematic analysis among nondialyzed individuals with
      diabetic renal disease, these data demonstrate that vascular and valvular
      calcification is present and often severe long before the disease progresses to
      ESRD. The data also suggest that the coronary artery and aortic wall
      calcification may represent atherosclerosis.

PMID- 12787419
TI  - A randomized controlled trial of blood flow and stenosis surveillance of
      hemodialysis grafts.
AB  - BACKGROUND: It is widely accepted that hemodialysis graft surveillance combined
      with correction of stenosis reduces thrombosis and prolongs graft survival.
      Nevertheless, few randomized controlled trials have evaluated this approach.
      METHODS: In this randomized controlled trial, 101 patients were assigned to
      control, flow (Qa), or stenosis groups, and were followed for up to 28 months.
      All patients had monthly Qa measured by ultrasound dilution and quarterly percent
      stenosis measured by duplex ultrasound. Referral for angiography was based on the
      following criteria: (1) control group (N = 34), clinical criteria; (2) flow group
      (N = 32), Qa <600 mL/min or clinical criteria; and (3) stenosis group (N = 35),
      stenosis>50% or clinical criteria. Stenosis >or=50% during angiography was
      corrected by preemptive percutaneous transluminal angioplasty (PTA). RESULTS: The
      preemptive PTA rate in the control group (0.22/patient year) was two thirds the
      rate in the flow group (0.34/patient year), and was highest in the stenosis group
      (0.65/patient year, P < 0.01). The percentage of grafts that thrombosed was
      similar in the control (47%) and flow groups (53%), but reduced in the stenosis
      group (29%, P = 0.10). Two-year graft survival was similar in the control (62%),
      flow (60%), and stenosis groups (64%) (P = 0.89). CONCLUSION: Qa and stenosis
      surveillance were not associated with improved graft survival, although
      thrombosis was reduced in the stenosis group. The most important factors in this
      result may be that monthly Qa and quarterly stenosis measurements were not
      accurate or timely indicators of risk of thrombosis or progressive stenosis. This
      study does not support the concept that Qa or stenosis surveillance are superior
      to aggressive clinical monitoring.

PMID- 12787421
TI  - Pharmacokinetics of oral micronized beta-estradiol in postmenopausal women
      receiving maintenance hemodialysis.
AB  - BACKGROUND: Although 11% of postmenopausal women with end-stage renal disease
      (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use
      remains poorly explored. Although there remains controversy surrounding the
      benefits of HRT, it may be of particular interest in this population, which has a
      high risk of bone loss and a fourfold increase in fracture risk compared to the
      general population. However, the appropriate dose of estrogen for use in
      postmenopausal women with ESRD is not known. The objective of this study was to
      evaluate the steady-state pharmacokinetics of oral micronized beta-estradiol in
      postmenopausal women with ESRD compared with postmenopausal women with normal
      renal function in order to determine equivalent dosing. METHODS: Six
      postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy
      postmenopausal controls received 14 days of micronized beta-estradiol (1.0 mg for
      control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained
      during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone
      binding globulin (SHBG) concentrations were determined. Free estradiol
      concentrations were calculated using a previously described method. RESULTS:
      Women with ESRD had significantly lower serum albumin (610 +/- 31 micromol/L vs.
      684 +/- 83 micromol/L) and SHBG (78 +/- 17 vs. 118 +/- 13 nmol/L) than control
      subjects. Total clearance of estradiol was not significantly different. Due to
      difference in binding, free estradiol concentrations were significant higher in
      ESRD women (53.2 +/- 17.7 pg/mL) than control women (43.5 +/- 8.7 pg/mL), despite
      receiving 50% of the dose. There was no significant difference in estrone
      concentrations. Clearance of both estradiol and estrone in the dialysate was
      minimal. CONCLUSION: Women with ESRD should receive approximately 50% of the dose
      typically prescribed to women without ESRD.

PMID- 12787420
TI  - Toxic acute tubular necrosis following treatment with zoledronate (Zometa).
AB  - BACKGROUND: Renal failure and toxic acute tubular necrosis (ATN) may be seen
      following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a
      new, highly potent bisphosphonate used in the treatment of hypercalcemia of
      malignancy. We report the first clinical-pathologic study of nephrotoxicity
      associated with this agent. METHODS: A cohort of six patients (four males and two
      females) with a mean age of 69.2 years received bisphosphonate therapy for
      multiple myeloma (five patients) or Paget's disease (one patient). In all
      patients, zoledronate was administered at a dose of 4 mg intravenously monthly,
      infused over at least 15 minutes, and the duration of therapy was mean 4.7 months
      (range, 3 to 9 months). RESULTS: All patients developed renal failure with a rise
      in serum creatinine from a mean baseline level of 1.4 mg/dL to 3.4 mg/dL. Renal
      biopsy revealed toxic ATN, characterized by tubular cell degeneration, loss of
      brush border, and apoptosis. Immunohistochemical staining revealed a marked
      increase in cell cycle-engaged cells (Ki-67 positive) and derangement in tubular
      Na+,K+-ATPase expression. Importantly, although all patients had been treated
      with pamidronate prior to zoledronate, no biopsy exhibited the characteristic
      pattern of collapsing focal segmental glomerulosclerosis observed in pamidronate
      nephrotoxicity. Following renal biopsy, treatment with zoledronate was
      discontinued and all six patients had a subsequent improvement in renal function
      (mean final serum creatinine, 2.3 mg/dL at 1 to 4 months of follow-up).
      CONCLUSION: The close temporal relationship between zoledronate administration
      and the onset of renal failure and the partial recovery of renal function
      following drug withdrawal strongly implicate this important and widely used agent
      in the development of toxic ATN.

PMID- 12787422
TI  - The cost-effectiveness of maintaining higher hemoglobin targets with
      erythropoietin in hemodialysis patients.
AB  - BACKGROUND: There is uncertainty regarding the appropriate target hemoglobin
      level in hemodialysis patients treated with erythropoietin (EPO). METHODS: We
      sought to determine the incremental cost-effectiveness of prescribing EPO to
      maintain different target hemoglobin levels, by incorporating the impact of EPO
      on health-related quality-of-life (HRQOL) issues and adopting the perspective of
      the health care purchaser. We evaluated the prescription of EPO to maintain
      target hemoglobin levels of 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, compared
      with 9.5 to 10.5 g/dL. Model outputs were quality-adjusted life expectancy and
      costs. RESULTS: The base case analysis estimated intravenous EPO requirements to
      be 3523, 5078, 6097, and 9341 units three times per week to maintain targets of
      9.5 to 10.5, 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, respectively. The cost
      per quality-adjusted life year (QALY) gained for the 11.0 to 12.0 g/dL target vs.
      9.5 to 10.5 g/dL was $55,295 US. For the 12.0 to 12.5 g/dL target compared to
      11.0 to 12.0 g/dL, and 14.0 g/dL target compared to 12.0 to 12.5 g/dL, the costs
      per QALY gained were $613,015 US and $828,215 US, respectively. In sensitivity
      analysis, clinically implausible reductions in hospitalization or EPO
      requirements associated with the two higher hemoglobin targets were required to
      make their incremental cost per QALY gained <$100,000 US. CONCLUSION: Dosing
      intravenous EPO to achieve hemoglobin targets of 11.0 to 12.0 g/dL appears to be
      associated with incremental cost per QALY gained of $50,000 to $60,000, compared
      with a hemoglobin target of 9.5 to 10.5 g/dL. Aiming for hemoglobin targets in
      excess of 12.0 g/dL is associated with unfavorable cost-effectiveness ratios and
      should not be undertaken based on current data.

PMID- 12787423
TI  - Change from three times a week on-line hemodiafiltration to short daily on-line
      hemodiafiltration.
AB  - BACKGROUND: Daily dialysis has shown excellent clinical results because a higher
      frequency of dialysis is more physiologic. On-line hemodiafiltration (OL-HDF) is
      a HDF technique that combines diffusion with high convection in which the
      dialysis fluid itself is used as a reinfusion solution. The aim of this study was
      to demonstrate the beneficial effect of the more effective dialysis schedule
      (daily dialysis) with the dialysis modality that offers the highest uremic toxin
      removal (on-line HDF). METHODS: Eight patients, six males and two females, on
      standard 4 to 5 hours three times a week OL-HDF (S-OL-HDF) were switched to daily
      OL-HDF (D-OL-HDF) 2 to 21/2 hours six times per week. Dialysis parameters were
      identical during both periods and only frequency and dialysis time of each
      session were changed. Tolerance, uremic toxin removal, urea kinetics, biochemical
      and anemia profiles, blood pressure, and left ventricular hypertrophy were
      evaluated. RESULTS: D-OL-HDF was well accepted and tolerated. The disappearance
      of postdialysis fatigue was rapidly reported by patients. Patients mantained the
      same [time average concentration (TAC) and weekly single-pool Kt/V (spKt/V)]
      throughout the study. However, equivalent renal urea clearance (EKR), standard
      Kt/V and weekly urea reduction ratio (URR) were increased during D-OL-HDF. Weekly
      urea, creatinine, osteocalcin, beta2-microglobulin, myoglobin, and prolactin
      reduction ratios were improved with D-OL-HDF. There was a significant decrease in
      predialysis plasma levels of urea, creatinine, acid uric, beta2-microglobulin and
      homocysteine over 6 months. Phosphate binders were reduced and antihypertensive
      drugs were stopped. A 30% regression of left ventricular mass was observed.
      CONCLUSION: The change from S-OL-HDF to D-OL-HDF was well tolerated.
      Disappearance of postdialysis fatigue, better dialysis adequacy, a higher removal
      of middle and large molecules, a reduction of phosphate binders, improvement of
      status nutritional, and an important reduction of cardiovascular risk factors
      were observed.

PMID- 12787424
TI  - Cytokine single nucleotide polymorphisms and intrarenal gene expression in
      chronic allograft nephropathy in children.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) have been reported to
      influence cytokine production. Certain cytokine high producer genotypes have been
      associated with an increased risk for acute rejection and chronic allograft
      dysfunction (CAD) after transplantation. Our study evaluates SNP distribution for
      transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and tumor
      necrosis factor-alpha (TNF-alpha) in pediatric renal transplant recipients and
      control individuals and correlates them to corresponding intrarenal gene
      expression. METHODS: SNPs for TGF-beta1 (codon 10 and 25), IL-10 (positions 
      1082, -819, -592) and TNF-alpha (position -308) were determined in 30 patients
      with stable graft function, in 75 patients with CAD, and in 173 control
      individuals by allele-specific polymerase chain reaction (PCR). Intrarenal
      cytokine gene expression was studied in 25 biopsies with chronic allograft
      nephropathy (CAN) and 27 normal kidney specimens by real-time reverse
      transcription (RT)-PCR. RESULTS: No difference in allele and genotype frequency
      was detected in any of the investigated groups. No correlation between genotype
      and intragraft cytokine gene expression was recognized in CAN patients. However,
      in normal kidney specimens, the low producer TGF-beta1 genotype at codon 10 was
      associated with significant lower TGF-beta1 mRNA expression. This association was
      not found for IL-10 or TNF-alpha. CONCLUSION: Our results do not support the
      proposition that certain specific cytokine genotypes for TGF-beta1, IL-10, and
      TNF-alpha are associated with CAD. Intrarenal cytokine gene expression only
      correlated to one TGF-beta1 SNP in normal kidney specimens. Since overall TGF
      beta1 expression was higher in transplanted patients compared to controls, this
      suggests that SNPs may not play a significant role once the immune system is
      activated.

PMID- 12787425
TI  - Regulation of apoptosis by lethal cytokines in human mesothelial cells.
AB  - BACKGROUND: Dysregulation of peritoneal cell death may contribute to the
      complications of peritoneal dialysis (PD). Chronic peritoneal dialysis and acute
      peritonitis are both associated with loss of mesothelial cells. In addition,
      acute peritonitis is characterized by sudden changes in the number of peritoneal
      leukocytes. However, the factors regulating peritoneal cell survival are poorly
      understood. METHODS: Peritoneal effluent cells and mesothelial cells cultured
      from peritoneal dialysis patients were studied. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) and flow cytometry were used to assess the expression of
      FasL and Fas mRNA and protein. Western blot was used to assess FasL and tumor
      necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). RT-PCR was used
      to study TRAIL and TRAIL receptor mRNA. Apoptosis was quantified by flow
      cytometry of DNA content and confirmed by morphology. RESULTS: Apoptotic cells,
      including apoptotic mesothelial cells, were present in the peritoneal effluent of
      stable peritoneal dialysis patients and patients with bacterial peritonitis. The
      lethal cytokines FasL and TRAIL were expressed by peritoneal effluent cells,
      while cultured mesothelial cells expressed FasL, Fas, and TRAIL receptors.
      Cultured mesothelial cells were sensitive to FasL-induced apoptosis. IFNgamma
      increased the cell surface expression of Fas and the sensitivity of mesothelial
      cells to FasL-induced apoptosis. In contrast to the effect of FasL, TNFalpha and
      TRAIL did not induce apoptosis in human mesothelial cells from peritoneal
      dialysis patients. CONCLUSION: Lethal cytokines, such as FasL, may contribute to
      peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. The
      role of other cytokines, such as TRAIL, remains undefined. Approaches in limiting
      mesothelial cell injury that interferes with apoptosis should be considered.

PMID- 12787426
TI  - Connective tissue growth factor and its regulation in the peritoneal cavity of
      peritoneal dialysis patients.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) is a fibrogenic cytokine that
      is highly expressed in wound healing and fibrotic lesions. The role of
      transforming growth factor-beta (TGF-beta) in fibrosis is well documented, and
      the emerging understanding that its fibrogenic actions are mediated through CTGF
      has provided an attractive target molecule for the modulation of matrix
      overproduction in fibrotic disease. The involvement of CTGF in the pathogenesis
      of peritoneal membrane fibrosis in peritoneal dialysis (PD) patients has not been
      investigated, and so the aim of this study was to ascertain whether CTGF is
      produced in the peritoneal cavity of PD patients and to investigate its
      regulation by cytokines. METHODS: Reverse transcription-polymerase chain reaction
      (RT-PCR), Northern blotting, and Western blotting were used to study CTGF
      expression by cultured human peritoneal mesothelial cells (HPMC) from peritoneal
      dialysis patients. Western blotting was used to detect CTGF expression in spent
      peritoneal dialysate from patients with and without peritonitis. RESULTS: RT-PCR
      analysis demonstrated the expression of CTGF mRNA in cultured primay HPMCs
      isolated from spent peritoneal effluent. The production of the major 36 to 38 kD
      CTGF protein doublet by HPMC in addition to a 23 to 25 kD proteolytically
      processed form was confirmed by Western blotting. Several molecular weight forms
      of CTGF (18 to 38 kD) were also detected by Western blotting in peritoneal
      dialysate, with levels markedly elevated during episodes of peritonitis. Northern
      and Western blot analysis revealed that CTGF mRNA and protein production by HPMC
      was up-regulated by TGF-beta, with mRNA levels significantly increasing above the
      control (P < 0.01). In contrast, platelet-derived growth factor (PDGF), epidermal
      growth factor (EGF), and tumor necrosis factor-alpha (TNF-alpha) had no
      measurable effects on CTGF mRNA expression. CONCLUSION: These results are the
      first to demonstrate the production of CTGF by HPMC and its presence in the
      peritoneal cavity of PD patients. The marked increase in CTGF levels by factors
      implicated in the development of peritoneal membrane fibrosis suggests its
      involvement in the underlying pathophysiologic mechanism(s).

PMID- 12787427
TI  - Health-related quality of life as a predictor of mortality and hospitalization:
      the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: We investigated whether indicators of health-related quality of life
      (HRQOL) may predict the risk of death and hospitalization among hemodialysis
      patients treated in seven countries, taking into account serum albumin
      concentration and several other risk factors for death and hospitalization. We
      also compared HRQOL measures with serum albumin regarding their power to predict
      outcomes. METHODS: We analyzed data from the Dialysis Outcomes and Practice
      Patterns Study (DOPPS), an international, prospective, observational study of
      randomly selected hemodialysis patients in the United States (148 facilities),
      five European countries (101 facilities), and Japan (65 facilities). The total
      sample size was composed of 17,236 patients. Using the Kidney Disease Quality of
      Life Short Form (KDQOL-SFTM), we determined scores for three components of HRQOL:
      (1) physical component summary (PCS), (2) mental component summary (MCS), and (3)
      kidney disease component summary (KDCS). Complete responses on HRQOL measures
      were obtained from 10,030 patients. Cox models were used to assess associations
      between HRQOL and the risk of death and hospitalization, adjusted for multiple
      sociodemographic variables, comorbidities, and laboratory factors. RESULTS: For
      patients in the lowest quintile of PCS, the adjusted risk (RR) of death was 93%
      higher (RR = 1.93, P < 0.001) and the risk of hospitalization was 56% higher (RR
      = 1.56, P < 0.001) than it was for patients in the highest quintile level. The
      adjusted relative risk values of mortality per 10-point lower HRQOL score were
      1.13 for MCS, 1.25 for PCS, and 1.11 for KDCS. The corresponding adjusted values
      for RR for first hospitalization were 1.06 for MCS, 1.15 for PCS, and 1.07 for
      KDCS. Each RR differed significantly from 1 (P < 0.001). For 1 g/dL lower serum
      albumin concentration, the RR of death adjusted for PCS, MCS, and KDCS and the
      other covariates was 1.17 (P < 0.01). Albumin was not significantly associated
      with hospitalization (RR = 1.03, P> 0.5). CONCLUSION: Lower scores for the three
      major components of HRQOL were strongly associated with higher risk of death and
      hospitalization in hemodialysis patients, independent of a series of demographic
      and comorbid factors. A 10-point lower PCS score was associated with higher
      elevation in the adjusted mortality risk, as was a 1 g/dL lower serum albumin
      level. More research is needed to assess whether interventions to improve quality
      of life lower these risks among hemodialysis patients.

PMID- 12787428
TI  - Model of robust induction of glomerulosclerosis in mice: importance of genetic
      background.
AB  - BACKGROUND: Increasing evidence suggests that genetic background plays an
      important role in the development of progressive glomerulosclerosis. The remnant
      kidney model (RKM) of progressive renal disease has been used extensively in
      rats. However, C57BL/6 mice are resistant to glomerulosclerosis with RKM induced
      by either pole amputation or renal artery ligation. A pole resection protocol,
      applied in 129/Sv mice, induced only mild glomerulosclerosis. We present here a
      highly reproducible, modified RKM approach to successfully establish a
      glomerulosclerosis model in mice. METHODS: Male C57BL/6 (N = 17), 129/Sv (N = 20)
      and Swiss-Webster (N = 3) mice underwent RKM as follows: the lower branch of the
      left renal artery was ligated to produce about one third infarct; the upper pole
      of the left kidney (about one third kidney size) was removed by cautery and the
      right kidney was nephrectomized to induce a total 5/6 nephrectomy (Nx). In some
      C57BL/6 mice, 7/8 nephrectomy was induced by removing additional renal mass from
      the upper pole of the left kidney by cautery. Systolic blood pressure (BP) was
      measured in conscious mice using a tail-cuff blood pressure monitor and animals
      were sacrificed at 9, 12, 18, and 24 weeks after nephrectomy. Kidneys were
      harvested for morphologic analysis. RESULTS: BP in C57BL/6 mice increased
      slightly after 5/6 nephrectomy over time without significant difference compared
      to baseline blood pressure except at 8 weeks (blood pressure at week 0, 98 +/- 1
      mm Hg; week 4, 105 +/- 2 mm Hg; week 8, 113 +/- 4 mm Hg; and week 12, 110 +/- 3
      mm Hg). Blood presssure remained normal in C57BL/6 mice at 18 weeks after 7/8
      nephrectomy (103 +/- 2 mm Hg). Blood pressure in 129/Sv mice increased
      significantly after 5/6 nephrectomy from 4 to 12 weeks (week 0, 112 +/- 3 mm Hg;
      week 4, 161 +/- 9 mm Hg; week 8, 166 +/- 5 mm Hg; and week 12, 176 +/- 5 mm Hg; P
      < 0.01 weeks 4, 8, and 12 vs. week 0 blood pressure). Urine protein excretion in
      C57BL/6 mice increased only at 4 weeks after 5/6 nephrectomy, and was back to
      normal at 8 and 12 weeks (week 0, 13.2 +/- 1.4 mg/24 hours; week 4, 20.5 +/- 1.8
      mg/24 hours; week 8, 18.8 +/- 1.6 mg/24 hours; and week 12, 17.2 +/- 1.2 mg/24
      hours, P < 0.05 week 4 vs. week 0). 129/Sv mice developed significant proteinuria
      12 weeks after 5/6 nephrectomy compared to their baseline and to levels achieved
      in C57BL/6 mice (week 0, 17.2 +/- 1 mg/24 hours; week 4, 14.9 +/- 1.8 mg/24
      hours; week 8, 23.8 +/- 6.7 mg/24 hours; and week 12, 36.3 +/- 6.6 mg/24 hours, P
      < 0.01 week 12 vs. week 0; P < 0.01 129/Sv vs. C57BL/6 at week 12). Mortality
      varied in response to nephrectomy injury in the different strains. Ten percent of
      C57BL/6 and 43% of 129/Sv died within 12 weeks after 5/6 nephrectomy. Although
      50% of C57BL/6 mice died by 12 weeks after 7/8 nephrectomy, there was only mild
      glomerulosclerosis (<5%) in C57BL/6 mice even at 24 weeks after 5/6 nephrectomy
      or 18 weeks after 7/8 nephrectomy. In contrast, glomerulosclerosis was marked in
      both 129/Sv mice and Swiss-Webster mice as early as 9 weeks after 5/6
      nephrectomy: 42% of glomeruli showed sclerosis in 129/Sv mice [average sclerosis
      index (SI), 0 to 4+ scale, 1.08] vs. 24% in Swiss-Webster mice (average SI,
      0.57). Tubulointerstitial fibrosis developed in parallel with glomerulosclerosis
      in both 129/Sv and Swiss-Webster mice. CONCLUSION: We conclude that genetic
      background is one of the important factors determining the susceptibility to the
      development of glomerulosclerosis in mice. We speculate that the superior effects
      of renal artery ligation plus cautery to produce glomerulosclerosis may result
      from higher blood pressure responses due to local ischemia activating the renin
      angiotensin system.

PMID- 12787429
TI  - Validation of endogenous controls for gene expression analysis in microdissected
      human renal biopsies.
AB  - BACKGROUND: The appropriate choice of an internal reference is critical for
      quantitative RNA analysis. However, no comparison of frequently used
      "housekeeping" genes is available for renal biopsy studies. METHODS:
      Microdissected biopsies from 165 patients, including a wide range of
      histopathologic diagnoses, were analyzed [immunoglobulin A (IgA) nephritis,
      membranous glomerulopathy, rapid progressive glomerulonephritis, minimal change
      disease, focal segmental glomerulosclerosis (FSGS), nephrosclerosis, diabetic
      nephropathy, interstitial nephritis, and controls]. Expression of three
      frequently used housekeeping genes [glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), 18S rRNA, and cyclophilin A] was examined by real-time reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Absolute expression
      values of reference genes obtained from the renal biopsies were related to each
      other. In tubulointerstitial compartment, a positive correlation coefficient (r)
      of 0.96 was observed between 18S rRNA and cyclophilin A. However, a subset of
      samples showed lower expression levels for GAPDH in relation to 18S rRNA or
      cyclophilin A, resulting in a decrease to r = 0.77 and r = 0.73, respectively,
      consistent with considerable mRNA regulation of GAPDH. In glomerular samples, a
      comparable low correlation between GAPDH versus 18S rRNA (r = 0.75) was obtained.
      CONCLUSION: Using a single housekeeper gene as reference for renal biopsy
      studies, differences in gene expression ratios may reflect regulation of the
      internal control rather than the mRNA under investigation. Relating the gene
      expression to several housekeepers in parallel (i.e., 18S rRNA and cyclophilin A)
      should result in robust expression data.

PMID- 12787430
TI  - Congenital ureteral obstruction: new technology, new targets.

PMID- 12787431
TI  - Unveiling mesangial mysteries.

PMID- 12787432
TI  - Podocin mutations in sporadic focal-segmental glomerulosclerosis occurring in
      adulthood.

PMID- 12787433
TI  - Mycophenolate mofetil prevents development of urinary protein in autoimmune
      nephritis.

PMID- 12787435
TI  - Myocardial function in Bartter's and Gitelman's syndromes.

PMID- 12787437
TI  - Ozonetherapy in a dialyzed patient with calcific uremic arteriolopathy.

PMID- 12787440
TI  - Retarding the progression of renal disease.

PMID- 12787445
TI  - Tri(propylene glycol) glycerolate diacrylate cross-linked polystyrene: a new
      resin support for solid-phase peptide synthesis.
AB  - A highly flexible, mechanically and chemically stable copolymer, tri(propylene
      glycol) glycerolate diacrylate cross-linked polystyrene (PS-TRPGGDA), was
      synthesized by the suspension polymerization and employed as a solid support for
      peptide synthesis. The beaded polymer support containing secondary hydroxyl
      functional groups in the cross-linker was used as the growth site for peptide
      synthesis. The procedure is unique and cost-effective in that it avoids the
      initial functionalization steps required for most of the styrene-based polymer
      supports. The resin was characterized by 13C-CP-MAS NMR spectroscopy and the
      morphologic features of the resin were investigated using scanning electron
      microscopy. Swelling studies conducted on the new support revealed that the PS
      TRPGGDA resin undergoes more effective swelling and solvation than PS-DVB resin
      in all solvents used in peptide synthesis. The efficiency of the new support was
      demonstrated by synthesizing a 'difficult' sequence Ala-Arg-(Ala)6-Lys and
      comparing it with commercially available Merrifield and Sheppard resins. The
      synthetic efficiency was further demonstrated by the synthesis of a 24-residue NR
      2A peptide substrate of calcium/calmodulin-binding peptide. The high yield and
      purity of the peptide synthesized on the novel support indicates the positive
      role of the flexible and hydrophilic cross-linking agent in the solid support.

PMID- 12787446
TI  - A comparative kinetic study on the singlet molecular oxygen-mediated
      photoxidation of alpha- and beta-chymotrypsins.
AB  - Kinetic aspects of the sensitized photooxidation of alpha- and beta-chymotrypsins
      have been studied at pH 6 and 8. The sensitization, employing classical
      O2(1Deltag)-photogenerators, such as xanthene dyes, is a kinetically intricate
      process because of the presence of ground state dye-protein associations and to
      the simultaneous participation of superoxide ion and singlet molecular oxygen
      [O2(1Deltag)]. Both proteins, that possess the same distribution pattern of
      photooxidizable amino acids, suffer a pure O2(1Deltag)-mediated photodynamic
      attack, using the carbonylic sensitizer Perinaphthenone. Overall and reactive
      rate constants for the O2(1Deltag)-quenching (in the order of 108 and 107/M/s,
      respectively), and rates of oxygen consumption determined by time-resolved,
      spectroscopic and polarographic methods indicate that alpha- and beta
      chymotrypsins are less photooxidizable at pH 6, as a result of an enhancement of
      the O2(1Deltag)-physical quenching component. In general terms, beta-chymotrypsin
      exhibits the greater overall proclivity to interact with O2(1Deltag), whereas
      structural factors, possibly evidenced by a higher exposure of the reactive
      tryptophan residues, impart an increased photooxidation degree to the proteins at
      pH 8, specially to the alpha-chymotrypsin.

PMID- 12787447
TI  - Design and function of a conformationally restricted analog of the influenza
      virus fusion peptide.
AB  - A conformationally restricted analog of the N-terminal 12-residue peptide segment
      of the HA2 subunit of the PPV/34, PR/8/34, and Jap/57 strains of influenza virus
      hemagglutinin was synthesized containing three residues of Calpha-methyl-valine.
      This peptide has a higher content of helical structure in the presence of 50%
      trifluoroethanol or when interacting with liposomes of egg phosphatidylcholine
      compared with the conformationally more flexible control peptide with the native
      sequence. The control and analog peptides had opposite effects on membrane
      curvature as measured by shifts in the bilayer-to-hexagonal phase transition
      temperature of a synthetic phosphatidylethanolamine derivative. The control
      peptide promoted more negative curvature, particularly at acidic pH and was also
      more potent than the analog in promoting lipid mixing. The results indicate that
      the ability of the peptide to sample a broader range of conformations is required
      for the influenza fusion peptide to destabilize membranes and that a rigid
      helical structure is less fusogenic. The difference between the two peptides and
      between pH 7.4 and pH 5.0 show a correlation between the ability to promote
      negative curvature and to accelerate lipid mixing.

PMID- 12787448
TI  - Synthesis, refolding and protective immune responses of a potential antigen for
      human Respiratory Syncytial Virus vaccine.
AB  - The design of new antigens with both high immunogenic and safety properties is of
      particular interest to vaccine against infectious diseases. In the present study,
      we describe the synthesis and the refolding of peptide G20 derived from the Human
      Respiratory Syncytial Virus (hRSV) G-protein. G20 (MEF G140-190 G144-158) is a
      peptide of 69 amino acids with two disulfide bridges, which comprises multiple
      protective B-cell epitopes. It was deleted of the T helper cell epitope 184-198
      of the RSV G-protein, which was found to induce pulmonary pathology after RSV
      challenge in mice. Interestingly, we showed in the present study that G20
      generated a highly protective antibody response against RSV challenge in Balb/c
      mice. Therefore, G20 represents a new potential antigen for an RSV vaccine.

PMID- 12787449
TI  - In vivo structure-activity studies on the dark-color-inducing neurohormone of
      locusts.
AB  - In the 11-residue long dark-color-inducing neurohormone (DCIN = [His7]
      corazonin), of locusts, from residue 2 to residue 11, one amino acid at each time
      was substituted by d-phenylalanine (d-Phe). The dark-color-inducing effect of
      these peptides was investigated in comparison with unaltered DCIN by a bioassay
      based on nymphs of a DCIN-deficient albino mutant of the migratory locust,
      Locusta migratoria. Substitution of any single amino acid by d-Phe always reduced
      the activity, but did not abolish it completely. Maximum inactivation was
      obtained after substitution of Gln4, Ser6, or Trp9. The latter two residues are
      within the partial sequence -Ser-Xxx-Gly-Trp- (Xxx = His in the DCIN) that seems
      to be important for the dark-color-inducing activity, as found also in another
      study (Insect Biochem. Mol. Biol. 32, 2002, 909). Gln4, however, is outside of
      this partial sequence. Minimal, although still considerable, inactivation
      occurred after substitution of Gly8, Phe3, or Asn11, despite the fact that Gly8
      is within the -Ser-Xxx-Gly-Trp- partial sequence. In conclusion, no single active
      core was found, indicating that the whole sequence of the DCIN is necessary to
      induce maximum darkening effect. No difference was found in the activity of the
      peptides in which Gly8 was substituted by d-Phe or by l-Phe. Therefore the -Ser
      Xxx-Gly-Trp- partial sequence does not seem to be stabilized by a type II beta
      turn. Nevertheless, existence of another kind of turn that includes this partial
      sequence is feasible. A single unsuccessful attempt was made to discover an
      antagonist to the DCIN.

PMID- 12787450
TI  - The biological consequences of replacing hydrophobic amino acids in deltorphin I
      with amphiphilic alpha-hydroxymethylamino acids.
AB  - New analogues of deltorphin I (DT I), in which the Phe residue in position 3, and
      the Val residue in position 5 or 6 are replaced with respective amphiphilic alpha
      hydroxymethylamino acid residues (HmAA), were synthesized and tested for receptor
      affinity and selectivity to mu and delta opioid receptors. The analogue with (R)
      HmPhe at position 3 lost receptor selectivity, as a result of a partial decrease
      of affinity to delta and a significant increase of affinity to mu receptors. In
      contrast, an analogue with (S)-HmPhe in the same position, was very potent and
      more specific to delta receptors than parent DT I. The analogue with (R)-HmVal at
      position 5 expressed higher delta affinity and selectivity than parent DT I. The
      analogue with other possible isomer (S)-HmVal was less selective for delta opioid
      receptors, as a result of decreasing affinity to delta and increasing affinity to
      mu receptors. The analogues with (R)- or (S)-HmVal in position 6 expressed
      equally low receptor affinity and selectivity. The data obtained support a
      previously proposed model of active conformation of deltorphins.

PMID- 12787451
TI  - Effect of preparation mode on Class II resin composite repair.
AB  - Complete removal of failed posterior resin composite fillings is time-expensive
      and involves the risk of removing sound tooth substance. In any case of failure
      within the composite material, intra-oral repair would be favourable. This in
      vitro study was conducted to examine the effect of different preparation and
      bonding modes on integrity of repaired restorations. Forty-eight direct Class II
      resin composite restorations (Syntac Classic/Tetric Ceram) were placed in
      extracted human third molars. The specimens were stored for 365 days and then
      replaced partially by removing the central part of the proximal box with all
      margins located in composite. The partial repairs were placed with the same
      materials after pre-treatment with a silicon carbide bur and Syntac Classic (n =
      8). Preparation modes have been (i) box-only parallel, (ii) box-only with
      undercuts, (iii) box with undercuts and additional occlusal retention. The
      repairs were performed either with (i) Tetric Ceram or with (ii) Tetric Flow as
      thin lining covered with Tetric Ceram. Before and after thermomechanical loading
      (100 000 cycles of 50 N and 2500 cycles between +5 and +55 degrees C in an
      artificial mouth), marginal quality between aged and freshly applied composite
      was evaluated by SEM at x200 magnification and microleakage was observed by light
      microscopy at x50 magnification. Box-only preparations exhibited a better fatigue
      resistance than preparations with additional occlusal retention. This observation
      was independent from the presence of undercuts (P < 0.05). An intermediary layer
      of flowable resin composite tended to result in better marginal quality, however,
      not being statistically significant.

PMID- 12787452
TI  - Investigation of the factors related to the formation of the buccal mucosa
      ridging.
AB  - The aim of this study was to clarify the factors related to the formation of the
      buccal mucosa ridging, which has been mentioned to be a clinical sign of
      clenching. Twenty-one individuals were investigated and divided into three
      groups: (i) those without buccal mucosa ridging, (ii) the buccal mucosa ridging
      located in all the posterior teeth region, and (iii) the buccal mucosa ridging
      corresponding only to the molar teeth region. A pressure sensor was used and
      placed at two points: first upper premolar and second upper molar. The recording
      tasks were: (i) silent reading at rest, (ii) light voluntary clenching, (iii)
      maximum voluntary clenching, (iv) holding the cheeks tightly against the teeth
      while light voluntary clenching, (v) holding the cheeks tightly against the teeth
      without tooth contact, (vi) pulling angle of mouth laterally while light
      voluntary clenching, (vii) pulling angle of mouth laterally without tooth contact
      and (viii) swallowing. No significant differences were found between groups in
      all the recording tasks except for the swallowing, at which significant
      difference (P < 0.05) was found between the groups of individuals having buccal
      mucosa ridging and without it. Based on these results it became clear that the
      buccal mucosa pressure exerted on the buccal aspect of teeth during swallowing
      plays an important role in the formation of buccal mucosa ridging.

PMID- 12787453
TI  - Effects of interocclusal appliances on EMG activity during parafunctional tooth
      contact.
AB  - To test the hypothesis that a flat plane interocclusal appliance affects the
      electromyographic (EMG) activity of the temporalis and masseter muscles in pain
      free individuals, maxillary splints were fabricated for 20 individuals who
      reported no history, signs or symptoms of myofascial pain or arthralgia as
      determined by two trained, independent examiners. Subjects were instructed to
      establish light tooth contact, maximum clenching, and moderate clenching
      with/without the splint in place (as determined by random assignment) while EMG
      data from the left and right temporalis and masseter muscles were recorded. A 5
      min biofeedback training session to relax the masticatory muscles was followed by
      a repetition of the tooth contact/clenching tasks with/without the splint in
      place. With the splint in place, the activity of the temporalis muscles decreased
      for all tasks, significantly for the left and right temporalis under maximal
      clenching and for the right temporalis under moderate clenching. In contrast, the
      activity of the masseter muscles increased under light and moderate clenching
      (significantly for the left masseter under moderate clenching) and decreased
      slightly under maximal clenching. The effectiveness of interocclusal appliances
      may be due to mechanisms other than redistribution of adverse loading.

PMID- 12787454
TI  - An electromyographic evaluation of the bilateral symmetry and nature of
      masticatory muscle activity in jaw deformity patients during normal daily
      activities.
AB  - This study was designed to investigate the nature of masticatory muscle activity
      and the balance in the bilateral symmetry of the masticatory muscle activity in
      jaw deformity patients. Fifteen patients (19.9 +/- 5.3 years) with lateral shift
      of the mandible caused by transverse craniofacial deformity and 15 controls (28.6
      +/- 1.9 years) were used as the subjects in this study. Surface electromyographic
      (EMG) activities were recorded from the bilateral masseter and anterior temporal
      muscles during daytime (142 min, including mealtime) and sleep (142 min). The
      averaged rectified EMG values were normalized with reference to the EMG amplitude
      induced by a 98-N bite force. Bilateral symmetry of masseter and anterior
      temporal muscle activities was examined using an asymmetry index (AI) for both
      the controls and the patients. The normalized activities of the masseter and
      anterior temporal muscles during normal daily activities were lower in patients
      than in the controls. Asymmetry indices in patients were significantly greater
      during usual daytime activities and sleep for the anterior temporal muscle and
      significantly smaller during sleep for the masseter muscle as compared with the
      controls. The results show that masticatory muscle activity is lower in these jaw
      deformity patients in association with more prominent asymmetry of anterior
      temporal muscle activity than in the controls. It is suggested that these
      findings are highly relevant to occlusal interference and instability because of
      malocclusion and lateral mandibular deviation.

PMID- 12787455
TI  - Relationship between occlusal plane determinants and craniofacial structures.
AB  - A cephalometric study was conducted on 34 complete denture wearers to investigate
      the relationship between the anatomical structures commonly used to determine the
      occlusal plane and the facial skeletal shape. The results showed no correlation
      between the shape of the skeletal face, the gonial angle and the length of the
      mandible versus the location of the retromolar pad, the occlusal plane and
      Camper's plane. However, a statistically significant linear correlation (P <
      0.0001) was found between the facial skeletal shape designated SN POG and the
      location of Camper's plane. Cephalometric analysis alone cannot determine the
      location of the occlusal plane in edentulous patients. Intra-oral structures
      should also be considered.

PMID- 12787456
TI  - Mandibular condyle movement during mastication of foods.
AB  - This study evaluated the mandibular condyle displacement on the working side
      while masticating certain foods with different textures. For referencing the
      mandibular condyle movement, the range of voluntary border movement of the
      mandibular condyle was determined based on the analysis of the sagittal, left
      lateral and right lateral border motion using Posselt's figure. The test foods
      consisted of cheese, peanuts, and beef jerky. During mastication of cheese and
      peanuts, the amount of displacement of the mandibular condyle in all directions
      was within the range of border movement. Significant posterior and superior
      shifts of the mandibular condyle were observed during mastication of beef jerky,
      compared with the findings obtained during border movement. Accordingly, it is
      suggested that prolonged mastication of hard fibrous foods, may stimulate the
      temporomandibular joint structure and mandibular dysfunction patients should
      limit their intake of such foods.

PMID- 12787457
TI  - Changes in properties of polyacid-modified composite resins (compomers) following
      storage in acidic solutions.
AB  - The interaction of three polyacid-modified composite resins (compomers) with
      various acidic storage solutions, and also water, over periods of time up to 6
      months has been studied and compared with those of a glass-ionomer and a
      composite resin. This interaction has been shown to vary in a complex way with
      length of storage and nature of the acid, and citric acid was found to be the
      most aggressive storage medium for glass-ionomer cement, and also for the
      compomers. The pure composite resin, by contrast, was relatively unaffected by
      all of the acid solutions examined. In all acids, the compomers showed a distinct
      buffering effect, i.e. they increased the pH towards neutral, as did the glass
      ionomer. The extent of this also varied with duration of storage and nature of
      the acid. The biaxial flexure strength was determined and found to be essentially
      unaffected by the complex chemical interactions with acidic storage solutions.
      Values obtained for the compomers were lower than those of the composite resin,
      but above those of the glass-ionomer. Fourier-transform infrared (FT-IR)
      spectroscopy was employed to study the changes in the compomers following storage
      in the aqueous media, but bands were broad and no detailed assignments could be
      made. There were changes in the region of the spectra associated with metal
      carboxylates however, and this indicates that the secondary acid-base reaction
      had occurred following water uptake.

PMID- 12787458
TI  - Visual observation of the dynamic flow of elastomer rubber impression material
      between the impression tray and oral mucosa while seating the impression tray.
AB  - The purpose of this study was to inspect visually, the dynamics of the impression
      flow at seating of the impression tray. The effects of the relief and the escape
      hole of the impression tray on the impression flow were also examined. Three
      types of the transparent impression tray (flat tray, relief tray and escape hole
      tray) were prepared. Transparent silicone polymer was put on the impression tray
      surface. Four drops of the dark blue silicone impression material was injected
      into the transparent silicone polymer on the impression tray. The impression tray
      was seated on the model of the denture-supporting mucosa. The movement of the
      four drops caused by the impression flow was visually recorded with the video
      camera and examined. The result for the flat tray showed that the impression
      material moved from inside to the outside. It was also shown that the speed of
      the moved impression material increased as the seating of the impression tray
      advanced. The results for the relief tray and the escape hole tray showed the
      effect of the relief and the escape hole prepared to the impression tray on the
      speed and the direction of the flow of the impression material.

PMID- 12787459
TI  - Functional magnetic resonance imaging of human jaw movements.
AB  - This study used functional magnetic resonance images (fMRI) to examine brain
      activity during clenching, gum chewing, and tapping tasks. It has been considered
      difficult to obtain sufficient fMRI data during jaw movement because the head
      motion associated with the jaw movements creates artifacts on the images. To
      avoid these artifacts, larger pixels were used, thus allowing some head motion of
      the subjects, and data from subjects where the heads were evaluated to have moved
      more than 0.5 mm were discarded. Further, all pixels obtained by fMRI were
      evaluated and pixels positively synchronized with the task, which were considered
      to show brain activity, were selected. Sufficient fMRI data was obtained from 30
      experiments, 10 sets for each task. During the clenching and tapping tasks, the
      activated pixels were in the sensory, motor and pre-motor cortexes, and in the
      sensory and motor cortexes but not in the pre-motor cortex during the gum chewing
      task. There appears to be no significant differences between right- and left
      hemispheres. It is conceivable that there are differences between voluntary jaw
      movements (clenching and tapping tasks) and mastication (gum chewing task)
      concerning the control of jaw movements.

PMID- 12787460
TI  - Effect of different filling materials in combination with intraradicular posts on
      the resistance to fracture of weakened roots.
AB  - The preservation and restoration of severely weakened pulpless teeth is a
      difficult and relatively unpredictable procedure. This study evaluated the
      resistance to fracture of experimentally weakened bovine roots internally
      reconstructed with different filling materials in combination with prefabricated
      post compared with restored roots that were relatively intact. The roots of 75
      mandibular bovine incisors with similar bulks were selected. Of these, 60 were
      internally prepared to standardized dimensions, thereby simulating weakness. All
      roots were filled with different restorative materials. The specimens were
      submitted to the fracture resistance testing with the application of a tangential
      compressive loading at an angle of 135 degrees in relation to the long axes of
      the roots. Results indicated statistically significant differences in relation to
      the root conditions. Weakened roots were less resistant to fracture than were
      controls. The roots restored with the resin cement demonstrated the lowest
      fracture resistance values, but statistically significant differences were
      observed only when compared with those restored by the resin-modified glass
      ionomer cement. Resin-modified glass-ionomer cement, polyacid-modified resin
      composite and resin composite behaved similarly without statistically significant
      differences among them. None of the materials evaluated were capable of achieving
      the fracture resistance recorded for unweakened controls.

PMID- 12787462
TI  - Masticatory performance with a prosthesis following maxillectomy: an analysis of
      43 cases.
AB  - To statistically evaluate the factors that influenced masticatory performance
      following Maxillectomy, masticatory performance was measured in 43 patients with
      a post-operative prosthesis by means of a spectrophotometer using adenosine
      triphosphate (ATP) granules. Our statistical analysis revealed that the number of
      occluding post-canine teeth and the patient's sex were factors that influenced
      masticatory performance and demonstrated that it was most important to improve
      occlusion in the pre-molar/molar region.

PMID- 12787461
TI  - Finite element analysis of strength characteristics of various resin based
      restorative materials in Class V cavities.
AB  - This study investigated the strength characteristics of various composites
      (Tetric Ceram, Tetric Flow, Prisma AP.H, Synergy Duo Shade, Synergy Compact, and
      Z 100) and compomers (Compoglass, Compoglass F, Dyract AP, F 2000) that were
      applied in a Class V cavity of a maxillary central incisor. The study was
      conducted by using a 3-dimensional finite element approach and in the study ansys
      package program was used. The tooth model had 294 elements and 420 nodes. The
      teeth considered were assumed to be subjected to an incisal load of 200 N acting
      at an angle of 26 degrees with the longitudinal axis of the tooth but the effects
      of different loading angles and different loads were also analysed. Hence, the
      loads of 100 and 400 N and the loading angles of 0 degrees representing bruxism
      and 90 degrees representing a traumatic load were also taken into consideration.
      The effects of the cavity preparation size were also studied. It was determined
      that any increase in the loading angle and/or the amount of the load resulted in
      a proportional increase in the stresses developed in the tooth. Furthermore it
      was also verified that, as a cavity weakens the tooth structure by creating a
      discontinuity in an intact tooth, the larger sized cavity preparations inevitably
      cause larger stresses to be developed in the tooth. Strictly from the mechanical
      point of view, the stresses developed in the restored teeth were determined to be
      inversely proportional with the modulus of elasticity of the restorative
      materials. Therefore within the scope of the study Z 100 was found to be superior
      to the other materials concerned.

PMID- 12787463
TI  - Finite element analysis of the effect of the bucco-lingual position of artificial
      posterior teeth under occlusal force on the denture supporting bone of the
      edentulous patient.
AB  - To improve the quality of the complete denture prosthesis, the bucco-lingual
      position of the artificial posterior teeth must be determined with consideration
      of the shape of the maxillary and mandibular residual ridge and the relationship
      between them. The arrangement of posterior artificial teeth should be considered
      not only for the denture stability but also for the avoidance of high pressure on
      the supporting structures. A two-dimensional finite element method program to
      investigate the statics for the contour of the complete denture and the residual
      ridge was developed. With this program, the effect of the bucco-lingual position
      of the artificial posterior teeth under occlusal force on the denture supporting
      bone could be investigated.

PMID- 12787464
TI  - Adhesive bonding of super-elastic titanium-nickel alloy castings with a phosphate
      metal conditioner and an acrylic adhesive.
AB  - The purpose of the current study was to evaluate the bonding characteristics of
      super-elastic titanium-nickel (Ti-Ni) alloy castings. Disk specimens were cast
      from a Ti-Ni alloy (Ti-50.85Ni mol%) using an arc centrifugal casting machine.
      High-purity titanium and nickel specimens were also prepared as experimental
      references. The specimens were air-abraded with alumina, and bonded with an
      adhesive resin (Super-Bond C & B). A metal conditioner containing a phosphate
      monomer (Cesead II Opaque Primer) was also used for priming the specimens. Post
      thermocycling average bond strengths (MPa) of the primed groups were 41.5 for Ti
      Ni, 30.4 for Ti and 19.5 for Ni, whereas those of the unprimed groups were 21.6
      for Ti, 19.3 for Ti-Ni and 9.3 for Ni. Application of the phosphate conditioner
      elevated the bond strengths of all alloy/metals (P < 0.05). X-ray fluorescence
      analysis revealed that nickel was attached to the debonded resin surface of the
      resin-to-nickel bonded specimen, indicating that corrosion of high-purity nickel
      occurred at the resin-nickel interface. Durable bonding to super-elastic Ti-Ni
      alloy castings can be achieved with a combination of a phosphate metal
      conditioner and a tri-n-butylborane-initiated adhesive resin.

PMID- 12787465
TI  - Influence of dentinal regions on bond strengths of different adhesive systems.
AB  - This in vitro study assessed comparatively the shear bond strengths of three
      composite resins, 3M Valux Plus (3MVP), Herculite (H), Clearfil AP-X (CAP-X), a
      polyacid modified composite resin Dyract (D), and a resin modified glass-ionomer
      materials Vitremer (V), to cervical and buccal dentine regions of extracted human
      molar teeth. Four different bonding systems, 3M ScotchBond Multipurpose (SB),
      Clearfil Liner Bond 2 (LB2), Opti Bond (OB), and Prime & Bond 2.1 (PB 2.1) were
      used with the manufacturer's respective composite and compomer materials. One
      hundred freshly extracted mandibular molar teeth were selected for this study.
      Flat buccal dentine surfaces were created on 50 teeth and cylindrical rods of the
      five materials were bonded to the dentine surfaces. For assessment of cervical
      bond strengths, the materials were bonded to mesial and distal enamel bordered
      occlusal dentinal surfaces of the remaining 50 teeth. The five groups of
      restorative procedures were applied as follows; Group 1: SB + 3MVP, Group 2: LB2
      + CAP-X, Group 3: OB + H, Group 4: PB2.1 + D, Group 5: Vitremer primer (VP) VP +
      V. Each restorative procedure thus had 20 specimens (10 buccal + 10 cervical).
      After 24 h of water storage (37 degrees C), the specimens were tested on a
      Universal Testing machine in shear with a cross head speed of 0.5 mm min-1. The
      bond strength values were calculated in MPa and the results were evaluated
      statistically using Kruskal-Wallis one-way/anova and Mann-Whitney U-tests. It was
      found that the bond strengths of SB + 3MVP, LB2 + CAP-X and VP + V to buccal
      dentine surfaces were significantly stronger (P < 0.05) than those to the occluso
      cervical dentine floors. When the bond strengths to the occluso-cervical dentine
      and buccal dentine surface were compared, there was no significant difference
      between the materials (P > 0.05). Vitremer was found the least successful
      adhesive material in terms of shear bond strength on both buccal and occluso
      cervical dentine surfaces.

PMID- 12787466
TI  - A 3-year clinical evaluation of a gallium restorative alloy.
AB  - Several alternative materials have been suggested to take the place of amalgam,
      because of the environmental toxic effects of its mercury component. One such
      material is gallium-based alloy restoratives. The aim of this in vivo study was
      to compare the long-term clinical performance of a commercial gallium alloy with
      an admixed high copper amalgam alloy. For this purpose, 32 gallium and 32 amalgam
      restorations were placed in molar teeth in 14 human subjects. All the selected
      patients had at least two molar teeth that required restoration. In this way both
      restoratives were used in the same oral cavity. The restorations were examined at
      baseline, 6 months, 1, 2 and 3 years. At baseline, six teeth restored with
      gallium alloy showed post-operative sensitivity, whereas none of the amalgams
      were sensitive. At the end of 3 years, only a few amalgam restorations showed
      slight surface tarnish and marginal integrity loss. None of them needed
      replacement. Of the 32 gallium restorations placed, five had to be removed
      because of sensitivity, corrosion and tooth fracture. Also dramatic surface
      roughness and corrosion were noticed in 12 gallium restoration. According to the
      results of this clinical study, gallium-based restoratives should not be used
      before their physical properties are improved.

PMID- 12787467
TI  - Following treatment of myogenous TMD patients with the temporomandibular opening
      index: an initial report.
AB  - Limitation of mandibular movement is one of the cardinal signs of
      temporomandibular disorders (TMD), usually assessed by measurement of maximum
      voluntary mouth opening. A new measure of assessing mandibular mobility, the
      temporomandibular opening index (TOI), is less dependent on variables such as
      age, gender and ramus length. It has also been found to be useful to categorize
      patients. This study examined changes in TOI as treatment progressed in a group
      of myogenous TMD patients. Seven patients with myogenous TMD were included in the
      study and the TOI determined at 0 and 2 weeks, 1 and 6 months after initiation of
      treatment. Treatment outcome was assessed on a 4 point scale, 0=none, 1=mild,
      2=moderate, and 3=severe. Headache, neckache, pain (joints and muscles) and joint
      sounds were assessed. Nine patients with no signs or symptoms of TMD were
      included to obtain a normal TOI. The mean TOI of the patient group was 16.4%
      (s.d.=11.2%) initially and 3.95% (s.d.=1.0%) at 6 months, while mean treatment
      scores changed from 12.57 (s.d.=3.05) to 1.43 (s.d.=1.90). The mean TOI of the
      control group was 3.63 (s.d.=0.74). A paired t-test showed that the TOI decreased
      significantly with time (P=0.02) while there was a concomitant decrease in
      treatment score (P=0.0003) over the same period. The TOI may be a useful method
      of following treatment of this group of myogenous TMD patients.

PMID- 12787469
TI  - Roll back malaria? The scarcity of international aid for malaria control.
AB  - The WHO announced the Roll Back Malaria (RBM) movement in 1998, with the goal of
      halving malaria deaths by 2010, and halving again by 2015. It is widely agreed
      that reaching this goal requires a major increase in international aid funding
      for malaria control, to a budget of perhaps 1.5 - 2.5 billion dollars annually.
      To ascertain whether progress is being made, we compiled data self-reported by
      the donors to the Development Assistance Committee of OECD, and also to ourselves
      directly. We find that, in fact, the total amount of international aid dedicated
      to malaria control, from the 23 richest donor countries plus the World Bank,
      remains in the range of 100 million dollars annually - a figure that is virtually
      unchanged since the start of RBM. This lack of progress toward increasing funding
      very seriously threatens RBM and demands that WHO regularly audit and report on
      malaria control funding, with the certainty that RBM will fail to meet its
      deadline of 2010 if this is not done.

PMID- 12787468
TI  - Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of
      DNA replication in Drosophila.
AB  - BACKGROUND: Cul1 is a core component of the evolutionarily conserved SCF-type
      ubiquitin ligases that target specific proteins for destruction. SCF action
      contributes to cell cycle progression but few of the key targets of its action
      have been identified. RESULTS: We found that expression of the mouse Cul1 (mCul1)
      in the larval wing disc has a dominant negative effect. It reduces, but does not
      eliminate, the function of SCF complexes, promotes accumulation of Cubitus
      interruptus (a target of SCF action), triggers apoptosis, and causes a small wing
      phenotype. A screen for mutations that dominantly modify this phenotype showed
      effective suppression upon reduction of E2F function, suggesting that compromised
      downregulation of E2F contributes to the phenotype. Partial inactivation of Cul1
      delayed the abrupt loss of E2F immunofluorescence beyond its normal point of
      downregulation at the onset of S phase. Additional screens showed that mild
      reduction in function of the F-box encoding gene slimb enhanced the mCul1
      overexpression phenotype. Cell cycle modulation of E2F levels is virtually absent
      in slimb mutant cells in which slimb function is severely reduced. This
      implicates Slimb, a known targeting subunit of SCF, in E2F downregulation. In
      addition, Slimb and E2F interacted in vitro in a phosphorylation-dependent
      manner. CONCLUSION: We have used genetic and physical interactions to identify
      the G1/S transcription factor E2F as an SCFSlmb target in Drosophila. These
      results argue that the SCFSlmb ubiquitin ligase directs E2F destruction in S
      phase.

PMID- 12787470
TI  - Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC
      class II molecules in LS1034 colorectal carcinoma cell line.
AB  - BACKGROUND: The expression of major histocompatibility complex class II (MHCII)
      antigens in both mouse and human tumors is rare, and these antigens are not
      easily inducible by IFN-gamma (IFNg). Since MHCII may play an important role in
      the development of host antitumor immune response, we explored the possibility of
      restoring MHCII inducibility in several IFNg-resistant tumor cell lines using
      protein kinase C (PKC) agonists phorbol myristate acetate (PMA) or Bryostatin.
      RESULTS: Tumor cells were co-cultured with various concentrations of PMA and IFNg
      for 48 hr. The expression of MHCII antigens and receptors IFNgR1 and IFNgR2 was
      determined by flow cytometry. We showed that the presence of as little as 0.1
      ng/ml of PMA in tissue culture restored the ability of weakly inducible LS1034
      colon carcinoma cells to express MHCII in response to IFNg (100 - 10,000 IU/ml)
      in a dose-dependent manner. Likewise, Bryostatin 1, as low as 10 ng/ml produced a
      5-6 fold upregulation of MHCII. The effect of PMA was not observed in two other
      poorly responding cell lines, MSTO-211H mesothelioma and HepG2 hepatocellular
      carcinoma, and was abrogated by relatively high concentrations of PKC inhibitors
      staurosporine (100 nM) and GF 109203X (1,000 nM). Both surface and intracellular
      staining of all cell lines with antibodies against IFNgR1 and IFNgR2 failed to
      detect any increase in IFNg receptor expression following incubation with PMA.
      CONCLUSION: In this study we showed that IFNg-inducibility of MHCII antigens in
      weakly inducible LS1034 colorectal carcinoma cell line can be rescued by
      concomitant incubation with PKC agonists. Bryostatin 1 may be considered for
      further investigation of IFNg-dependent MHCII induction in resistant tumors in
      vivo.

PMID- 12787471
TI  - Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics,
      free energy calculations and experiment.
AB  - BACKGROUND: Charging of transfer-RNA with cognate amino acid is accomplished by
      the aminoacyl-tRNA synthetases, and proceeds through an aminoacyl adenylate
      intermediate. The lysyl-tRNA synthetase has evolved an active site that
      specifically binds lysine and ATP. Previous molecular dynamics simulations of the
      heat-inducible Escherichia coli lysyl-tRNA synthetase, LysU, have revealed
      differences in the binding of ATP and aspects of asymmetry between the nominally
      equivalent active sites of this dimeric enzyme. The possibility that this
      asymmetry results in different binding affinities for the ligands is addressed
      here by a parallel computational and biochemical study. RESULTS: Biochemical
      experiments employing isothermal calorimetry, steady-state fluorescence and
      circular dichroism are used to determine the order and stoichiometries of the
      lysine and nucleotide binding events, and the associated thermodynamic
      parameters. An ordered mechanism of substrate addition is found, with lysine
      having to bind prior to the nucleotide in a magnesium dependent process. Two
      lysines are found to bind per dimer, and trigger a large conformational change.
      Subsequent nucleotide binding causes little structural rearrangement and
      crucially only occurs at a single catalytic site, in accord with the simulations.
      Molecular dynamics based free energy calculations of the ATP binding process are
      used to determine the binding affinities of each site. Significant differences in
      ATP binding affinities are observed, with only one active site capable of
      realizing the experimental binding free energy. Half-of-the-sites models in which
      the nucleotide is only present at one active site achieve their full binding
      potential irrespective of the subunit choice. This strongly suggests the
      involvement of an anti-cooperative mechanism. Pathways for relaying information
      between the two active sites are proposed. CONCLUSIONS: The asymmetry uncovered
      here appears to be a common feature of oligomeric aminoacyl-tRNA synthetases, and
      may play an important functional role. We suggest a manner in which catalytic
      efficiency could be improved by LysU operating in an alternating sites mechanism.

PMID- 12787472
TI  - Mesiodens--diagnosis and management of a common supernumerary tooth.
AB  - Mesiodentes are the most common supernumerary teeth, occurring in 0.15% to 1.9%
      of the population. Given this high frequency, the general dentist should be
      knowledgeable about the signs and symptoms of mesiodentes and appropriate
      treatment. The cause of mesiodentes is not fully understood, although
      proliferation of the dental lamina and genetic factors have been implicated.
      Mesiodentes can cause delayed or ectopic eruption of the permanent incisors,
      which can further alter occlusion and appearance. It is therefore important for
      the clinician to diagnose a mesiodens early in development to allow for optimal
      yet minimal treatment. Treatment options may include surgical extraction of the
      mesiodens. If the permanent teeth do not erupt in a reasonable period after the
      extraction, surgical exposure and orthodontic treatment may be required to ensure
      eruption and proper alignment of the teeth. In some instances, fixed orthodontic
      therapy is also required to create sufficient arch space before eruption and
      alignment of the incisor(s). Early diagnosis allows the most appropriate
      treatment, often reducing the extent of surgery, orthodontic treatment and
      possible complications. This paper outlines the causes and modes of presentation
      of mesiodentes, and presents guidelines for diagnosis and management of
      nonsyndromic mesiodentes.

PMID- 12787473
TI  - Esthetic periodontal considerations in orthodontic treatment--the management of
      excessive gingival display.
AB  - This paper examines various esthetic periodontal considerations during
      orthodontic treatment. The management of excessive gingival display caused by
      altered passive eruption is reviewed, with emphasis on causes, recognition,
      diagnosis and surgical management of this problem. A case of orthodontic
      treatment of excessive gingival display associated with altered passive eruption
      of the maxillary incisors is reviewed to demonstrate appropriate management. With
      proper diagnosis, soft-tissue periodontal procedures after completion of
      orthodontic treatment can enhance the patient's final appearance.

PMID- 12787474
TI  - Rapid palatal expansion in the young adult: time for a paradigm shift?
AB  - A 19-year-old man presented for correction of a malocclusion that included a
      transverse maxillary deficiency. The patient was informed that he required
      orthognathic surgery to expand his upper jaw and correct his malocclusion, but he
      refused surgical expansion. Recent evidence indicates that rapid palatal
      expansion can be used without surgery in young adults; the decision was therefore
      made to treat the patient nonsurgically. Rapid palatal expansion of the maxillary
      arch was accomplished by means of a Hyrax appliance, with post-treatment
      radiographs revealing an opening of the midpalatal suture. The belief still
      persists among some clinicians that young adult patients require orthognathic
      surgery for palatal expansion, despite recent evidence supporting a nonsurgical
      approach after closure of the midpalatal suture.

PMID- 12787475
TI  - Enamel reduction procedures in orthodontic treatment.
AB  - Various combinations of enamel reduction procedures can be used to create space
      between teeth, to correct discrepancies between mandibular and maxillary teeth
      and to correct morphologic anomalies during orthodontic treatment. In particular,
      acid-enhanced interproximal enamel reduction significantly reduces surface
      roughness. This article presents a review of the literature on enamel reduction
      procedures.

PMID- 12787476
TI  - A pilot investigation of enamel reduction procedures.
AB  - OBJECTIVE: To test and describe the use of various combinations of mechanical and
      chemical techniques for enamel reduction to obtain a smooth surface. METHODS:
      Bovine teeth (2 surfaces on each of 32 teeth) were used. The teeth were mounted
      in blocks of dental plaster, which were then mounted in a vise. The mesiodistal
      enamel contact areas were reduced by various combinations of mechanical and
      chemical aids. The mesiodistal width of each tooth was measured with a digital
      caliper after initial reduction of the enamel surface and again after polishing.
      The teeth were subsequently prepared and mounted for scanning electron
      microscopy. RESULTS: All combinations yielded statistically significant enamel
      reduction (p < 0.05). The use of acid stripping in conjunction with mechanical
      procedures produced especially smooth enamel surfaces. CONCLUSIONS: Steps must be
      taken to ensure that a smooth enamel surface remains after enamel reduction and
      polishing. It is recommended that conventional enamel etchants be added to the
      polishing procedure. Enamel reduction can increase available space, but the
      quantity of enamel that can be removed without adverse consequences should be
      carefully evaluated.

PMID- 12787477
TI  - Theoretical investigation of the triphosphate forms of azidothymidine and
      thymidine.
AB  - In this paper we investigate (using AM1 semi-empirical as well as HF methods at
      the STO-3G, 3-21G, 6-31G, 6-31G* and 6-31+G** level) the conformations,
      geometrical parameters, Mulliken charges, and solvation effects of the
      triphosphate form of AZT (AZTTP), as well as the thymidine nucleotide (dTTP)
      structure. Our calculated geometrical parameters and Mulliken charges, with and
      without solvation effects, are correlated with recent experimental results.

PMID- 12787478
TI  - Agmatine reduces hydrogen peroxide in mesangial cells under high glucose
      conditions.
AB  - Agmatine, an amine and organic cation, reduced H(2)O(2) that was generated by
      hyperglycemia, and transcription factors such as NF-kappaB and AP-1 activity in
      the mesangial cells that were exposed to high glucose. However, spermine which
      shares a strong nucleophilic structure with agmatine decreased the H(2)O(2)
      levels and AP-1, but not the NF-kappaB activity. Possible roles for agmatine and
      spermine in decreasing fibronectin are discussed, and the signaling pathway for
      agmatine-reduced fibronectin accumulation is presented.

PMID- 12787479
TI  - Suppression of fatty acid synthase by dietary polyunsaturated fatty acids is
      mediated by fat itself, not by peroxidative mechanism.
AB  - This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that
      were supplemented with vitamin E on lipid peroxidation, glutathione-dependent
      detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS)
      expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets
      containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla
      oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil
      (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances,
      an estimate of lipid peroxidation, were not significantly different among the
      dietary groups. The glutathione peroxidase, glutathione reductase, and
      glutathione S-transferase activities were all elevated by the polyunsaturated
      fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated
      fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA
      contents decreased in rats that were fed the 10% fat diets, particularly
      polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet.
      Similarly, the inhibitory effect was the greatest in fish oil. These results
      suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has
      a suppressive effect on lipogenic enzyme.

PMID- 12787480
TI  - Retinoic acid-induced Golgi apparatus disruption in F2000 fibroblasts: a model
      for enhanced intracellular retrograde transport.
AB  - Retinoic acid (RA) can transform the Golgi apparatus (GA) into a diffuse vacuolar
      aggregate and increase the toxicity of some immunotoxins that enter into cells by
      receptor-mediated endocytosis. An ultramorphological study of the RA-induced GA
      disruption was performed on F2000 fibroblasts. Cultures were treated with 0.11 to
      30 microM RA for 7-180 min. The endocytosis of Limax flavus agglutinin-peroxidase
      conjugate (LFA), and the interactions between a phorbol ester (PMA) and RA
      concerning GA disruption, were examined. Exposure to 0.33 microM RA for 20 min
      transformed the GA into vacuolar aggregate. These vacuoles were not involved in
      endocytosis since they remained unstained after endocytosis of LFA. However, the
      lysosomes were involved in endocytosis, as they were strongly stained. Therefore,
      a RA-induced shift towards lysosomal routing of the entered LFA was presumed.
      Exposure to PMA made cells resistant to the Golgi-disturbing effects of RA,
      indicating that protein kinase C plays an important role in this process.

PMID- 12787481
TI  - Styrylpyrone derivative induces apoptosis through the up-regulation of Bax in the
      human breast cancer cell line MCF-7.
AB  - In the fight against cancer, novel chemotherapeutic agents are constantly being
      sought to complement existing drugs. Various studies have presented evidence that
      the apoptosis that is induced by these anticancer agents is implicated in tumor
      regression, and Bcl-2 family genes play a part in apoptosis following treatment
      with various stimuli. Here, we present data that a styrylpyrone derivative (SPD)
      that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on
      the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in
      MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt
      mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting
      and immunostaining revealed up-regulation of the proapoptotic Bax protein
      expression. SPD, however, did not affect the expression of the anti-apoptotic
      protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent
      on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.

PMID- 12787483
TI  - Production of superoxide dismutase by Deinococcus radiophilus.
AB  - The production of superoxide dismutase (SOD) varied in Deinococcus radiophilus,
      the UV resistant bacterium, depending upon different phases of growth, UV
      irradiation, and superoxide treatment. A gradual increase in total SOD activity
      occurred up to the stationary phases. The electrophoretic resolution of the SOD
      in cell extracts of D. radiophilus at each growth phase revealed the occurrence
      of MnSOD throughout the growth phases. The SOD profiles of D. radiophilus at the
      exponential phase received oxidative stress by the potassium superoxide treatment
      or UV irradiation also revealed the occurrence of a single SOD. However, these
      treatments caused an increase in SOD activity. The data strongly suggest that D.
      radiophilus has only one species of SOD as a constitutive enzyme, which seems to
      be a membrane-associated protein.

PMID- 12787482
TI  - Conditional replication of a recombinant adenovirus studied using neomycin as a
      selective marker.
AB  - An E1B-defective adenovirus, named r2/Ad carrying the neo expression cassette,
      was constructed by homologous recombination. The construction, selection (using
      neomycin as a selective marker), and propagation of the recombinant virus was
      performed in human embryonic kidney 293 cells (HEK 293). An in vitro study
      demonstrated that this recombinant virus has the ability to replicate in and lyse
      some p53-deficient human tumor cells such as human glioma tumor cells (U251) and
      human bladder cells (EJ), but not in some cells with functional p53, such as
      human adenocarcinoma cells (A549) and human fibroblast cells (MRC-5). Also, based
      on the cytopathic effect (CPE), it was demonstrated, under identical conditions,
      that the U251 cells were more sensitive to r2/Ad replication than the EJ cells.
      In this paper, we report that r2/Ad could be very useful in studying the in vitro
      selective replication of E1B-defective adenovirus and has great potential in
      cancer gene therapy.

PMID- 12787484
TI  - The EphA8 receptor phosphorylates and activates low molecular weight
      phosphotyrosine protein phosphatase in vitro.
AB  - Low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) has been
      implicated in modulating the EphB1-mediated signaling pathway. In this study, we
      demonstrated that the EphA8 receptor phosphorylates LMW-PTP in vitro. In
      addition, we discovered that mixing these two proteins leads to EphA8
      dephosphorylation in the absence of phosphatase inhibitors. Finally, we
      demonstrated that LMW-PTP, modified by the EphA8 autokinase activity, possesses
      enhanced catalytic activity in vitro. These results suggest that LMW-PTP may also
      participate in a feedback-control mechanism of the EphA8 receptor autokinase
      activity in vivo.

PMID- 12787485
TI  - Ex vivo cytotoxicity of the Bacillus thuringiensis Cry4B delta-endotoxin to
      isolated midguts of Aedes aegypti larvae.
AB  - The pathological effect of the Bacillus thuringiensis Cry delta- endotoxins on
      susceptible insect larvae had extensive damage on the midgut epithelial cells. In
      this study, an ex vivo assay was devised for assessing the insecticidal potency
      of the cloned Cry4B mosquito-larvicidal protein that is expressed in Escherichia
      coli. Determination of toxicity was carried out by using a cell viability assay
      on the midguts that were dissected from 5-day old Aedes aegypti mosquito larvae.
      After incubation with the toxin proteins, the number of viable epithelial cells
      was determined photometrically by monitoring the quantity of the bioreduced
      formazan product at 490 nm. The results showed that the 65-kDa trypsin-activated
      Cry4B toxin exhibited toxic potency ca. 3.5 times higher than the 130-kDa Cry4B
      protoxin. However, the trypsin-treated products of the non-bioactive Cry4B mutant
      (R158A) and the lepidopteran-specific Cry1Aa toxin displayed relatively no ex
      vivo activity on the mosquito-larval midguts. The ex vivo cytotoxicity studies
      presented here confirms data that was obtained in bioassays.

PMID- 12787486
TI  - Identification of novel target proteins of cyclic GMP signaling pathways using
      chemical proteomics.
AB  - For deciphering the cyclic guanosine monophosphate (cGMP) signaling pathway, we
      employed chemical proteomics to identify the novel target molecules of cGMP. We
      used cGMP that was immobilized onto agarose beads with linkers directed at three
      different positions of cGMP. We performed a pull-down assay using the beads as
      baits on tissue lysates and identified 9 proteins by MALDI-TOF (Matrix-Assisted
      Laser Desorption/Ionization Time-of-Flight) mass spectrometry. Some of the
      identified proteins were previously known cGMP targets, including cGMP-dependent
      protein kinase and cGMP-stimulated phosphodiesterase. Surprisingly, some of the
      coprecipitated proteins were never formerly reported to associate with the cGMP
      signaling pathway. The competition binding assays showed that the interactions
      are not by nonspecific binding to either the linker or bead itself, but by
      specific binding to cGMP. Furthermore, we observed that the interactions are
      highly specific to cGMP against other nucleotides, such as cyclic adenosine
      monophosphate (cAMP) and 5?'-GMP, which are structurally similar to cGMP. As one
      of the identified targets, MAPK1 was confirmed by immunoblotting with an anti
      MAPK1 antibody. For further proof, we observed that the membrane-permeable cGMP
      (8-bromo cyclic GMP) stimulated mitogen-activated protein kinase 1 signaling in
      the treated cells. Our present study suggests that chemical proteomics can be a
      very useful and powerful technique for identifying the target proteins of small
      bioactive molecules.

PMID- 12787487
TI  - Single-strand DNA binding of actinomycin D with a chromophore 2-amino to 2
      hydroxyl substitution.
AB  - A modified actinomycin D was prepared with a hydroxyl group that replaced the
      amino group at the chromophore 2-position, a substitution known to strongly
      reduce affinity for double-stranded DNA. Interactions of the modified drug on
      single-stranded DNAs of the defined sequence were investigated. Competition
      assays showed that 2-hydroxyactinomycin D has low affinity for two
      oligonucleotides that have high affinities (K(a) = 5-10 x 10(6) M(-1) oligomer)
      for 7-aminoactinomycin D and actinomycin D. Primer extension inhibition assays
      performed on several single-stranded DNA templates totaling around 1000 nt in
      length detected a single high affinity site for 2-hydroxyactinomycin D, while
      many high affinity binding sites of unmodified actinomycin D were found on the
      same templates. The sequence selectivity of 2-hydroxyactinomycin D binding is
      unusually high and approximates the selectivity of restriction endonucleases.
      Binding appears to require a complex structure, including residues well removed
      from the polymerase pause site.

PMID- 12787488
TI  - The effects of a high-fat or high-sucrose diet on serum lipid profiles, hepatic
      acyl-CoA synthetase, carnitine palmitoyltransferase-I, and the acetyl-CoA
      carboxylase mRNA levels in rats.
AB  - The purpose of this study was to investigate the effects of altering relative
      intakes of fat and carbohydrates on serum lipid profiles, hepatic acyl-CoA
      synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I), and the acetyl-CoA
      carboxlyase (ACC) mRNA level in Sprague-Dawley rats. For four weeks the rats were
      fed either an AIN-76 diet or one of its modified diets that were supplemented
      with 20% beef tallow (high-fat diet, HF) and 66.3% sucrose (high-sucrose diet,
      HS). The HS group had significantly higher serum triglyceride and total
      cholesterol concentrations when compared with the other groups. Serum LDL
      cholesterol concentrations in the HS and HF groups were significantly higher when
      compared to the normal diet (ND) group. Serum HDL-cholesterol levels of the ND
      and HS groups were significantly higher than those of the HF group. The hepatic
      total lipid level of the HF group was significantly higher than those of other
      groups; triglyceride levels of the HS and HF groups were significantly higher
      than those of the ND group. Hepatic ACS mRNA levels of the HF group were
      significantly higher than those of the ND group. Hepatic CPT-I mRNA levels were
      higher in the HF group than other groups. Also, ACC mRNA levels in the liver
      increased in the HF group. In conclusion, changes in the composition of dietary
      fat and carbohydrates could affect the hepatic ACS, CPT-I, and ACC mRNA levels.
      These results facilitate our understanding of the coordinated regulation of the
      ACS, CPT-I, and ACC mRNA levels and will serve to enhance our understanding of
      the molecular mechanisms that underlie the regulation of fatty acid metabolism.

PMID- 12787489
TI  - Stimulation of gamma-aminobutyric acid synthesis activity in brown rice by a
      chitosan/glutamic acid germination solution and calcium/calmodulin.
AB  - Changes in the concentrations of gamma-aminobutyric acid (GABA), soluble calcium
      ions, glutamic acid, and the activity of glutamate decarboxylase (GAD) were
      investigated in non-germinated vs. germinated brown rice. Brown rice was
      germinated for 72 h by applying each of the following solutions: (1) distilled
      water, (2) 5 mM lactic acid, (3) 50 ppm chitosan in 5 mM lactic acid, (4) 5 mM
      glutamic acid, and (5) 50 ppm chitosan in 5 mM glutamic acid. GABA concentrations
      were enhanced in all of the germinated brown rice when compared to the non
      germinated brown rice. The GABA concentration was highest in the
      chitosan/glutamic acid that germinated brown rice at 2,011 nmol/g fresh weight,
      which was 13 times higher than the GABA concentration in the non-germinated brown
      rice at 154 nmol/g fresh weight. The concentrations of glutamic acid were
      significantly decreased in all of the germinated rice, regardless of the
      germination solution. Soluble calcium and GAD were higher in the germinated brown
      rice with the chitosan/glutamic acid solution when compared to the rice that was
      germinated in the other solutions. GAD that was partially purified from
      germinated brown rice was stimulated about 3.6-fold by the addition of calmodulin
      in the presence of calcium. These data show that the germination of brown rice in
      a chitosan/glutamic acid solution can significantly increase GABA synthesis
      activity and the concentration of GABA.

PMID- 12787491
TI  - Microplate assay measurement of cytochrome p450-carbon monoxide complexes.
AB  - Cytochrome P450 in microsomes can be quantitated using the characteristic 450 nm
      absorption peak of the CO adduct of reduced cytochrome P450. We developed a
      simple microplate assay method that is superior to previous methods. Our method
      is less laborious, suitable for analyzing many samples, and less sensitive to
      sample aggregation. Microsome samples in microplate wells were incubated in a CO
      chamber rather than bubbled with CO gas, and then reduced with sodium
      hydrosulfite solution. This modification allowed a reliable and reproducible
      assay by effectively eliminating variations between estimations.

PMID- 12787490
TI  - Regulation of the gene encoding glutathione synthetase from the fission yeast.
AB  - The fission yeast cells that contained the cloned glutathione synthetase (GS)
      gene showed 1.4-fold higher glutathione (GSH) content and 1.9-fold higher GS
      activity than the cells without the cloned GS gene. Interestingly, gamma
      glutamylcysteine synthetase activity increased 2.1-fold in the S. pombe cells
      that contained the cloned GS gene. The S. pombe cells that harbored the multicopy
      number plasmid pRGS49 (containing the cloned GS gene) showed a higher level of
      survival on solid media with cadmium chloride (1 mM) or mercuric chloride (10
      microM) than the cells that harbored the YEp357R vector. The 506 bp upstream
      sequence from the translational initiation point and N-terminal 8 amino acid
      coding region were fused into the promoterless beta-galactosidase gene of the
      shuttle vector YEp367R to generate the fusion plasmid pUGS39. Synthesis of beta
      galactosidase from the fusion plasmid pUGS39 was significantly enhanced by
      cadmium chloride and NO-generating S-nitroso-N-acetylpenicillamine (SNAP) and
      sodium nitroprusside (SN). It was also induced by L-buthionine-(S,R)-sulfoximine,
      a specific inhibitor of gamma-glutamylcysteine synthetase (GCS). We also found
      that the expression of the S. pombe GS gene is regulated by the Atf1-Spc1-Wis1
      signal pathway.

PMID- 12787492
TI  - Nanog: a new recruit to the embryonic stem cell orchestra.
AB  - In this issue of Cell, and add a new transcriptional operating system to the
      known Oct4 and Stat3 systems required for early embryonal stem cell potency and
      self-renewal. Nanog, a homeobox transcription factor, plays a crucial role in the
      second embryonic cell fate specification following formation of the blastocyst.

PMID- 12787493
TI  - Fingering the ends: how to make new telomeres.
AB  - Telomerase-mediated healing of broken chromosomes gives rise to terminal
      deletions and is repressed in most organisms. In ciliated protozoa, however,
      chromosome fragmentation and de novo telomere addition are part of the
      developmental program. Work by in this issue of Cell indicates that in Euplotes
      crassus, this is mediated through switching between different telomerase reverse
      transcriptase isoforms.

PMID- 12787494
TI  - CUE'd up for Monoubiquitin.
AB  - The first structures have been obtained for complexes between CUE domains and
      monoubiquitin, one by NMR (Kang et al., this issue of Cell) and one by X-ray
      crystallography (Prag et al., this issue of Cell), thus providing insights into
      ubiquitin recognition by CUE domains. Structural comparisons suggest that
      different CUE surfaces can interact with ubiquitin, indicating that not all CUE
      domains are created equal.

PMID- 12787495
TI  - Periplasmic chaperones--preservers of subunit folding energy for organelle
      assembly.
AB  - The periplasmic PapD-like chaperones have long been known to be necessary for the
      assembly of bacterial surface organelles. New structural work now suggests that
      they control assembly by arresting subunit folding. This step may be required to
      preserve energy for fiber formation.

PMID- 12787496
TI  - Regeneration: if they can do it, why can't we?
AB  - The therapeutic potential of stem cells and nuclear cloning has led to renewed
      interest in classical models of regeneration. This longstanding problem is
      undergoing a renaissance spurred by the availability of new techniques that
      finally allow analysis on the cellular and molecular level.

PMID- 12787497
TI  - From DNA to genomes in 50 years.

PMID- 12787498
TI  - Developmentally programmed gene elimination in Euplotes crassus facilitates a
      switch in the telomerase catalytic subunit.
AB  - The primary function of telomerase is to maintain preexisting telomere tracts. In
      the ciliate Euplotes crassus, however, telomerase RNP structure and substrate
      recognition are altered during macronuclear development to facilitate de novo
      telomere addition. We found that E. crassus harbors three TERT genes encoding the
      telomerase catalytic subunit that not only vary in their nucleotide and predicted
      protein sequences, but also in their expression profiles. Expression of EcTERT-1
      and -3 correlates with the requirement for telomere maintenance, while that of
      EcTERT-2 correlates with de novo telomere synthesis. All three genes appear to
      require ribosomal frameshifting for expression of catalytically active protein.
      The transcriptionally active form of EcTERT-2 exists only transiently in mated
      cells and is absent from the vegetative macronucleus. Thus, telomerase expression
      in Euplotes is controlled by unique regulatory mechanisms that culminate in a
      developmental switch to a different catalytic subunit with properties suited to
      de novo telomere addition.

PMID- 12787499
TI  - Riboswitches control fundamental biochemical pathways in Bacillus subtilis and
      other bacteria.
AB  - Riboswitches are metabolite binding domains within certain messenger RNAs that
      serve as precision sensors for their corresponding targets. Allosteric
      rearrangement of mRNA structure is mediated by ligand binding, and this results
      in modulation of gene expression. We have identified a class of riboswitches that
      selectively recognizes guanine and becomes saturated at concentrations as low as
      5 nM. In Bacillus subtilis, this mRNA motif is located on at least five separate
      transcriptional units that together encode 17 genes that are mostly involved in
      purine transport and purine nucleotide biosynthesis. Our findings provide further
      examples of mRNAs that sense metabolites and that control gene expression without
      the need for protein factors. Furthermore, it is now apparent that riboswitches
      contribute to the regulation of numerous fundamental metabolic pathways in
      certain bacteria.

PMID- 12787500
TI  - Structure and biogenesis of the capsular F1 antigen from Yersinia pestis:
      preserved folding energy drives fiber formation.
AB  - Most gram-negative pathogens express fibrous adhesive virulence organelles that
      mediate targeting to the sites of infection. The F1 capsular antigen from the
      plague pathogen Yersinia pestis consists of linear fibers of a single subunit
      (Caf1) and serves as a prototype for nonpilus organelles assembled via the
      chaperone/usher pathway. Genetic data together with high-resolution X-ray
      structures corresponding to snapshots of the assembly process reveal the
      structural basis of fiber formation. Comparison of chaperone bound Caf1 subunit
      with the subunit in the fiber reveals a novel type of conformational change
      involving the entire hydrophobic core of the protein. The observed conformational
      change suggests that the chaperone traps a high-energy folding intermediate of
      Caf1. A model is proposed in which release of the subunit allows folding to be
      completed, driving fiber formation.

PMID- 12787501
TI  - Development of genetic circuitry exhibiting toggle switch or oscillatory behavior
      in Escherichia coli.
AB  - Analysis of the system design principles of signaling systems requires model
      systems where all components and regulatory interactions are known. Components of
      the Lac and Ntr systems were used to construct genetic circuits that display
      toggle switch or oscillatory behavior. Both devices contain an "activator module"
      consisting of a modified glnA promoter with lac operators, driving the expression
      of the activator, NRI. Since NRI activates the glnA promoter, this creates an
      autoactivated circuit repressible by LacI. The oscillator contains a "repressor
      module" consisting of the NRI-activated glnK promoter driving LacI expression.
      This circuitry produced synchronous damped oscillations in turbidostat cultures,
      with periods much longer than the cell cycle. For the toggle switch, LacI was
      provided constitutively; the level of active repressor was controlled by using a
      lacY mutant and varying the concentration of IPTG. This circuitry provided nearly
      discontinuous expression of activator.

PMID- 12787502
TI  - Mechanism of ubiquitin recognition by the CUE domain of Vps9p.
AB  - Coupling of ubiquitin conjugation to ER degradation (CUE) domains are
      approximately 50 amino acid monoubiquitin binding motifs found in proteins of
      trafficking and ubiquitination pathways. The 2.3 A structure of the Vps9p-CUE
      domain is a dimeric domain-swapped variant of the ubiquitin binding UBA domain.
      The 1.7 A structure of the CUE:ubiquitin complex shows that one CUE dimer binds
      one ubiquitin molecule. The bound CUE dimer is kinked relative to the unbound CUE
      dimer and wraps around ubiquitin. The CUE monomer contains two ubiquitin binding
      surfaces on opposite faces of the molecule that cannot bind simultaneously to a
      single ubiquitin molecule. Dimerization of the CUE domain allows both surfaces to
      contact a single ubiquitin molecule, providing a mechanism for high-affinity
      binding to monoubiquitin.

PMID- 12787503
TI  - Solution structure of a CUE-ubiquitin complex reveals a conserved mode of
      ubiquitin binding.
AB  - Monoubiquitination serves as a regulatory signal in a variety of cellular
      processes. Monoubiquitin signals are transmitted by binding to a small but
      rapidly expanding class of ubiquitin binding motifs. Several of these motifs,
      including the CUE domain, also promote intramolecular monoubiquitination. The
      solution structure of a CUE domain of the yeast Cue2 protein in complex with
      ubiquitin reveals intermolecular interactions involving conserved hydrophobic
      surfaces, including the Leu8-Ile44-Val70 patch on ubiquitin. The contact surface
      extends beyond this patch and encompasses Lys48, a site of polyubiquitin chain
      formation. This suggests an occlusion mechanism for inhibiting polyubiquitin
      chain formation during monoubiquitin signaling. The CUE domain shares a similar
      overall architecture with the UBA domain, which also contains a conserved
      hydrophobic patch. Comparative modeling suggests that the UBA domain interacts
      analogously with ubiquitin. The structure of the CUE-ubiquitin complex may thus
      serve as a paradigm for ubiquitin recognition and signaling by ubiquitin binding
      proteins.

PMID- 12787504
TI  - The homeoprotein Nanog is required for maintenance of pluripotency in mouse
      epiblast and ES cells.
AB  - Embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocysts
      grow infinitely while maintaining pluripotency. Leukemia inhibitory factor (LIF)
      can maintain self-renewal of mouse ES cells through activation of Stat3. However,
      LIF/Stat3 is dispensable for maintenance of ICM and human ES cells, suggesting
      that the pathway is not fundamental for pluripotency. In search of a critical
      factor(s) that underlies pluripotency in both ICM and ES cells, we performed in
      silico differential display and identified several genes specifically expressed
      in mouse ES cells and preimplantation embryos. We found that one of them,
      encoding the homeoprotein Nanog, was capable of maintaining ES cell self-renewal
      independently of LIF/Stat3. nanog-deficient ICM failed to generate epiblast and
      only produced parietal endoderm-like cells. nanog-deficient ES cells lost
      pluripotency and differentiated into extraembryonic endoderm lineage. These data
      demonstrate that Nanog is a critical factor underlying pluripotency in both ICM
      and ES cells.

PMID- 12787505
TI  - Functional expression cloning of Nanog, a pluripotency sustaining factor in
      embryonic stem cells.
AB  - Embryonic stem (ES) cells undergo extended proliferation while remaining poised
      for multilineage differentiation. A unique network of transcription factors may
      characterize self-renewal and simultaneously suppress differentiation. We applied
      expression cloning in mouse ES cells to isolate a self-renewal determinant. Nanog
      is a divergent homeodomain protein that directs propagation of undifferentiated
      ES cells. Nanog mRNA is present in pluripotent mouse and human cell lines, and
      absent from differentiated cells. In preimplantation embryos, Nanog is restricted
      to founder cells from which ES cells can be derived. Endogenous Nanog acts in
      parallel with cytokine stimulation of Stat3 to drive ES cell self-renewal.
      Elevated Nanog expression from transgene constructs is sufficient for clonal
      expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels. Cytokine
      dependence, multilineage differentiation, and embryo colonization capacity are
      fully restored upon transgene excision. These findings establish a central role
      for Nanog in the transcription factor hierarchy that defines ES cell identity.

PMID- 12787507
TI  - Principles of assessment from a clinical perspective.
AB  - Physicians apply assessments every day in clinical practice. Common clinical
      practice is impossible without measurements and tests. Testing looks rather
      straightforward: a test result is either positive or negative. Unfortunately,
      this simplicity is not in keeping with truth. At the base of measuring and
      testing in clinical practice lies the assumption of uncertainty: we do not know
      whether a patient has a disease, we can only estimate the probability that he has
      a disease by performing a (chain of) test(s). Every test result leaves open the
      chance that a wrong decision is taken on the basis of the test result. It is a
      challenge for the clinician to get a better insight into this process, as well as
      to minimize the chance of wrong decisions. By using a number of clinical
      examples, we describe here the principles of assessment from two different
      perspectives: the perspective of the test, and the perspective of the individual
      patient. The former perspective incorporates test-specific characteristics, such
      as sensitivity, specificity, accuracy and cut-off levels, and the latter deals
      with individual probabilities from a 'Bayesian' concept.

PMID- 12787506
TI  - Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate
      outgrowth of embryonic axons.
AB  - Axon outgrowth is the first step in the formation of neuronal connections, but
      the pathways that regulate axon extension are still poorly understood. We find
      that mice deficient in calcineurin-NFAT signaling have dramatic defects in axonal
      outgrowth, yet have little or no defect in neuronal differentiation or survival.
      In vitro, sensory and commissural neurons lacking calcineurin function or NFATc2,
      c3, and c4 are unable to respond to neurotrophins or netrin-1 with efficient
      axonal outgrowth. Neurotrophins and netrins stimulate calcineurin-dependent
      nuclear localization of NFATc4 and activation of NFAT-mediated gene transcription
      in cultured primary neurons. These data indicate that the ability of these
      embryonic axons to respond to growth factors with rapid outgrowth requires
      activation of calcineurin/NFAT signaling by these factors. The precise parsing of
      signals for elongation turning and survival could allow independent control of
      these processes during development.

PMID- 12787508
TI  - How to assess musculoskeletal conditions. History and physical examination.
AB  - Musculoskeletal conditions are common, their impact is pervasive and they are a
      major burden on health and social care. However, they are poorly managed because
      of lack of priority and inadequate competencies due to limited medical education
      in this spectrum of conditions. The ability to take a clear history and perform a
      competent examination are core skills to the appropriate management of
      musculoskeletal problems. This chapter outlines an approach that is followed by
      most specialists in rheumatology, orthopaedics or rehabilitation that can be used
      to teach other clinicians going into primary care or at the beginning of
      specialist training.

PMID- 12787509
TI  - How to assess musculoskeletal conditions. Prognostics.
AB  - Both patients and clinicians confronted with rheumatic disease need prognostic
      information to direct their management strategies. Prognosis refers to the
      prediction of outcome of disease. Clinicians confronted with prognostic problems
      in individual patients usually have to rely on evidence from prognostic studies
      on prognostic factors or clinical prediction models. Prognostic factors are
      patient characteristics that can be used to predict the outcome of disease.
      Clinical prediction models are sets of prognostic factors developed by logistic
      regression modelling. These models estimate the probabilities of the various
      forms of outcome of a disease and they can be valuable prognostic tools in daily
      clinical practice. To judge whether an article on prognosis fulfils the necessary
      methodological standards and contains relevant information, clinicians can use a
      number of guidelines that are described in this chapter. To find out whether the
      results of a prognostic study are applicable to individual patients in daily
      practice, the clinician should obtain clarity on three aspects: (i)
      generalizability, (ii) the possibility of extrapolating the results to the
      particular clinical situation, and (iii) feasibility. Decision analysis values
      the information provided by prognostic testing insofar as it alters treatment
      strategies. The treatment threshold is the probability of a particular disease
      outcome for which the net risks of treatment and no treatment are equal.
      Treatment is indicated if the probability of the disease outcome is higher than
      the treatment threshold.

PMID- 12787510
TI  - How to assess musculoskeletal conditions. Assessment of disease activity.
AB  - The concept of disease activity is useful for characterizing chronic rheumatic
      diseases and their current degree of severity. Disease activity should be clearly
      differentiated from damage, which is irreversible. A number of requirements must
      be met in order to make a measure of disease activity acceptable and valid.
      Methods for measurement have been developed in the areas of biological,
      radiographic, ultrasound and computerized imaging techniques. Recently, a
      particular effort has been made to develop questionnaires in the form of complex
      indices, derived from the observations of physicians, and self-report
      questionnaires for patients. Such assessments of disease activity are available
      for most of the chronic inflammatory rheumatic diseases. They are particularly
      relevant at a time when new biological drug therapy is being developed. Research
      effort is needed to develop more instruments suitable for use in clinical
      practice for individual patients.

PMID- 12787511
TI  - Assessment of pain in patients with rheumatic diseases.
AB  - Pain is the most prominent symptom in people with musculoskeletal disorders and
      the most common reason for patients to seek medical help. However, pain generally
      is not recorded quantitatively in usual medical care. A quantitative measure of
      pain is not needed in acute medical care but is essential over long periods as
      patients and health professionals cannot gauge accurately changes in levels of
      pain over years. The experience of pain is subjective, and early efforts by
      health professionals to estimate pain through an 'objective' measure of pain
      status were useful in clinical research but not in clinical care. Over the last
      three decades, self-report questionnaires have been developed in which a patient
      may record quantitatively a pain score, as well as other data concerning clinical
      status, which may be repeated over time to discern whether patients are improved,
      similar or worse. The most robust quantitative pain measure appears to be a
      simple 10-cm visual analogue scale (VAS) which can be completed by the patient
      and scored by a health professional in less than 30 s. These data cannot be
      obtained from any source other than the patient. Pain scores are correlated with
      'objective' measures such as radiographs, laboratory tests and physical
      examination findings, but more strongly correlated with scores for functional
      status and psychological distress in patients with rheumatic diseases. It is
      recommended that quantitative assessment of pain be included at each visit in
      routine rheumatology care, along with assessment of functional disability, global
      status and other patient variables, using a patient self-report questionnaire to
      improve patient care.

PMID- 12787512
TI  - Assessment of the impact of disease on the individual.
AB  - From the medical or disease perspective, patients' functioning, disability and
      health are seen primarily as the consequences or the impact of a disease or
      condition. In this perspective, self-administered health status instruments are
      used primarily to evaluate the effects of drug treatments or surgical
      interventions. The interpretation of these measures is generally based on scales
      and scores and not on individual items. Currently used instruments are reviewed
      and an algorithm for the selection of instruments is provided. In the
      rehabilitation or disability perspective, patients' functioning and health is
      associated with and not merely a consequence of, a condition or disease. The
      basis for the understanding of functioning, disability and health--in association
      with the condition but also the personal and contextual factors--is WHO's
      International Classification of Functioning, Disability and Health or ICF. This
      chapter illustrates the use of the ICF framework for structuring patients'
      problems, and the use of condition-specific ICF-Core-Sets to check for problems
      typically encountered in patients with a given condition.

PMID- 12787513
TI  - Laboratory assessment in musculoskeletal disorders.
AB  - Autoimmune-mediated musculoskeletal disorders feature the presence and pathogenic
      role of circulating autoantibodies and autoreactive T cells. Determination of
      these autoantibodies provides crucial information to establish the diagnosis of
      these diseases. In addition, the determination of these antibodies may have
      prognostic value or may be used to monitor response to treatment or to predict
      relapse of disease. We first address the main characteristics of several
      autoantibody assays that are considered to be clinically most relevant. These
      include rheumatoid factor (RF), anti-cyclic citrullinated antibody (anti-CCP),
      antinuclear autoantibodies (ANA), anti-double-stranded DNA antibodies, antibodies
      to extractable nuclear antigens (ENA), and antineutrophil cytoplasmic
      autoantibodies (ANCA). Subsequently we provide a brief overview of the most
      important musculoskeletal disorders, such as rheumatoid arthritis, systemic lupus
      erythematosus, Sjogren's syndrome, systemic sclerosis/CREST,
      polymyositis/dermatomyositis and vasculitis. Our main goal was to address the
      role of the determination of autoantibodies in the diagnosis and follow-up of
      musculoskeletal disorders.

PMID- 12787514
TI  - Radiography in the assessment of musculoskeletal conditions.
AB  - Plain film radiography is the most widely used imaging technique for diagnosing
      and monitoring the progression of chronic inflammatory and degenerative joint
      diseases. Advanced imaging techniques that are better suited for detecting soft
      tissue inflammation are available, but they are more costly and some of them may
      expose the patient to higher doses of radiation. Plain film radiographs are
      inexpensive, easy to generate, can be compared with baseline and prospective
      films, and provide a permanent, reproducible record. Radiographs can easily
      detect the features that are specific to various rheumatological disorders, and
      serial radiography can be used to assess response to therapy by measuring
      erosions, joint space narrowing, and other disease-specific features. This
      chapter discusses the use of radiography for diagnosing and differentiating
      various rheumatic joint diseases, specifically rheumatoid arthritis, psoriatic
      arthritis, ankylosing spondylitis and osteoarthritis. The most frequently used
      scoring systems that are used to assess and monitor the severity and progression
      of these disorders are briefly described.

PMID- 12787516
TI  - The costs of musculoskeletal disease: health needs assessment and health
      economics.
AB  - Arthritis and musculoskeletal conditions dominate the national illness burden
      worldwide. This chapter presents information on the different types of societal
      and individual impacts of musculoskeletal conditions, and describes the
      appropriate way to evaluate and present these effects. There are three types of
      'costs' associated with musculoskeletal conditions: direct, indirect and
      intangible. The direct costs of care are those associated with ambulatory and
      inpatient medical care; these costs may be borne by the patient or society. The
      indirect costs are those paid and unpaid activities, such as employment,
      schooling and homemaking, that result from disability associated with the health
      condition; these costs may be borne by employers, society or the individual
      patient. The intangible costs of the disease are pain, emotional impairment,
      health worry and other effects on the patient's quality of life. All of these
      components of costs may, and should be, accurately measured to get the full
      picture of the burden of musculoskeletal conditions.

PMID- 12787515
TI  - Imaging of the musculoskeletal system: magnetic resonance imaging,
      ultrasonography and computed tomography.
AB  - In the last decade, musculoskeletal imaging has rapidly expanded largely due to
      the imaging capabilities of magnetic resonance imaging and ultrasound. These
      modalities have increased the clinical understanding and mechanisms of arthritis
      and are assuming increasing importance in the diagnosis of arthritis; more
      recently, they have been used to monitor therapy. This chapter reviews recent
      imaging studies relevant to rheumatic diseases.

PMID- 12787520
TI  - Septic arthritis.
AB  - This chapter describes a rational approach to septic arthritis based on sound
      principles of pathology and therapeutics. Early diagnosis and prompt treatment
      are essential if normal function of the infected joint is to be restored. In any
      acute joint disease, infection must be suspected, and if present, detected. It is
      important to identify causative bacteria in order to administer the correct
      antibiotic. The clinical features are different in neonates, children and adults.
      Diagnosis is not usually difficult and may be aided by diagnostic ultrasound and
      arthrocentesis. Both antibiotics and joint lavage are essential parts of
      management. Successful outcome is based on effective treatment and results in
      normal joint function. Ineffective or delayed treatment may be crippling.

PMID- 12787521
TI  - Gonococcal arthritis.
AB  - Gonococcal arthritis results from blood dissemination of Neisseria gonorrhoeae
      from primary sexually acquired mucosal infection. The disease has become rare in
      Western countries since the introduction of effective control programmes, but it
      still needs to be recognized promptly to avoid systemic, potentially life
      threatening involvement, destructive changes associated with chronic arthritis
      and spread of the infection. Sexually active women are predominantly affected.
      Clinical features include polyarthralgia, sometimes migratory, tenosynovitis,
      arthritis, constitutional symptoms and skin lesions, which are mild and easily
      unnoticed. True arthritis occurs in less than 50% of cases. Primary mucosal
      infection may be asymptomatic.N. gonorrhoeae is a fragile micro-organism which is
      difficult to culture. Sampling of blood, synovial fluid, skin lesion, genito
      urinary tract, pharynx and rectum must be performed before starting antibiotics.
      Samples should be plated immediately on fresh, pre-warmed appropriate media and
      sent quickly to the laboratory. Culture of N. gonorrhoeae is of tremendous
      importance not only for definite diagnosis but also for determination of drug
      susceptibility. When culture is negative, rapid response to antimicrobial
      treatment will allow a probable diagnosis. Penicillin resistance has developed
      worldwide in recent years, and penicillin is no longer the initially recommended
      antibiotic for gonococcal arthritis. Patients should be started on a third
      generation cephalosporin and later switched to ampicillin or penicillin only when
      sensitivity to these antimicrobials has been demonstrated. Oral therapy
      substitutes the intravenous or intramuscular route after signs and symptoms have
      improved, in order to complete 7 days of antimicrobial therapy. Effusions should
      be aspirated until disappearance. Purulent effusions are rare but may require
      longer antibiotic treatment. The patient's sexual partner must be examined and
      treated. Patients should be tested and eventually treated for Chlamydia, syphilis
      and HIV, and educated about the sexual mode of transmission and means of
      preventing sexually transmitted diseases.

PMID- 12787522
TI  - Infection and arthritis. Infection of prosthetic joints.
AB  - Infection of prosthetic joints is one of the most devastating complications
      following replacement surgery. The size of the problem, the diagnostic puzzle,
      bacteriological findings and treatment modalities are highlighted.

PMID- 12787523
TI  - Arthritis associated with enteric infection.
AB  - Reactive arthritis is classically seen following infection with enteric pathogens
      such as Yersinia, Salmonella, Campylobacter and Shigella. Inflammatory arthritis
      has also been described following other enteric infection with organisms such as
      Clostridium difficile, Brucella and Giardia. Furthermore, arthritis is seen in
      Whipple's disease, caused by the actinomycete Tropheryma whippelii. This chapter
      reviews the current understanding of these conditions (with the exception of
      Brucella, which is discussed in a subsequent chapter). The epidemiology is
      reviewed, and the contribution of both host and organism to the aetiology and
      pathogenesis is discussed with particular discussion of the role of HLA-B27 in
      host susceptibility. Recent work exploring evidence for traffic of pathogenic
      organisms to the joint is highlighted. A practical approach to the diagnosis and
      management of the condition is then formulated based, where possible, on clinical
      trial evidence.

PMID- 12787524
TI  - Lyme disease (Lyme borreliosis).
AB  - Lyme borreliosis (Lyme disease) is a systemic infectious disease with a wide
      spectrum of symptoms affecting the skin, the heart, and the nervous and
      musculoskeletal systems. Lyme borreliosis is caused by the spirochaete Borrelia
      burgdorferi and transmitted by ticks. The disease occurs in endemic pockets with
      an incidence of from 50 to more than 100 cases per 100,000 inhabitants. Despite
      increasing knowledge about the virulence factors of the spirochaetes and the
      immune response of the host, many aspects of the pathogenesis, for example of
      chronic treatment-resistant disease, are still a matter of debate. The diagnosis
      is based on clinical findings and confirmed by serology. Diagnostic problems
      arise from patients with non-specific symptoms and a positive IgG serology. In
      about 80% of the patients, the disease can be cured by adequate antibiotic
      therapy. Evidence-based guidelines for treatment have been recently published.
      The only vaccine to prevent Lyme disease, licensed in the USA, has been
      discontinued due to disappointing sales despite good efficacy and tolerability.

PMID- 12787526
TI  - Geographically specific infections and arthritis, including rheumatic syndromes
      associated with certain fungi and parasites, Brucella species and Mycobacterium
      leprae.
AB  - This overview is designed to introduce the reader to the broad spectrum of
      rheumatic syndromes associated with certain fungal and parasitic diseases,
      brucellosis and leprosy. Musculoskeletal disorders caused by fungi are uncommon
      and difficult to diagnose, particularly in the early stages. Deep fungal
      infections involve-in order of frequency-bone, soft tissues and joints. Rare but
      well-defined rheumatic syndromes occur in a variety of parasitic diseases.
      Brucellosis remains a major challenge to both human public health and clinical
      acumen in many countries today. The arthritis of leprosy deserves wider
      recognition and study as it contributes to disability and may hold clues to the
      mechanism of inflammation in other rheumatic disorders. All of the above may
      afflict residents in endemic areas and occasionally appear far from the source of
      origin in travellers or migrants, and usually cause diagnostic confusion.

PMID- 12787525
TI  - Articular manifestations of human immunodeficiency virus infection.
AB  - Prospective studies of HIV-positive and HIV-negative individuals, longitudinal
      prospective studies of HIV-positive patients and the African experience with
      spondyloarthropathies have provided support for a direct role of HIV infection in
      producing a variety of articular manifestations. The most common manifestations
      are arthralgia and the spectrum of spondyloarthropathies, but distinct entities
      such as HIV-associated arthritis and the painful articular syndrome have also
      been reported. Although initial reports described patients with mainly asymmetric
      oligoarthritis, a polyarticular presentation is now seen frequently. In
      Caucasians, HIV-associated reactive arthritis resembles reactive arthritis in non
      HIV-infected persons. Reactive arthritis, psoriatic arthritis and
      undifferentiated spondyloarthropathy were uncommon in Africa and are now detected
      more often with the HIV epidemic. Although early reports in Western communities
      reported asymmetrical oligoarthritis as the usual pattern, polyarticular
      involvement is now seen frequently. Intravenous drug abuse is the most likely
      risk factor for septic arthritis, even in HIV-infected persons in Western
      communities, while HIV infection itself may be more important in developing
      countries where most patients do not receive highly active antiretroviral therapy
      (HAART). Recent reports have drawn attention to the development of avascular
      necrosis of the bone in HIV-positive patients and the risk factors include HAART
      itself, complications of HAART, HIV infection per se or concomitant conventional
      risk factors. Many patients respond to conventional symptomatic therapy, and
      disease-modifying drug therapy is necessary for patients who have persistent and
      progressive arthritis. The use of HAART can modify the prevalence or expression
      of the articular syndromes.

PMID- 12787527
TI  - Virus-associated arthritis.
AB  - The occurrence of arthritis in patients who were infected by a virus has been
      widely observed. In some cases, the clinical appearance seems to resemble that of
      rheumatoid arthritis. The mechanism by which the viral infection proceeds to the
      arthritic manifestation is, however, still to be investigated. Several biological
      and immunological pathways are suggested to be involved in the pathogenesis. The
      representatives of such potentially 'arthritogenic' viruses include human T-cell
      lymphotropic virus type I (HTLV-I), which causes destructive inflammatory
      arthritis in model animals. Other examples are hepatitis C virus and rubella
      virus. Clinical and pathological features of these virus-induced forms of
      arthritis are discussed.

PMID- 12787528
TI  - Arthritis associated with tuberculosis.
AB  - There has been a resurgence in tuberculosis (TB) worldwide. Approximately 2
      billion people have latent infection, 8 million would develop active TB annually,
      and 2-3 million would die due to TB. With this resurgence, cases with
      extrapulmonary TB have also shown an increase. Approximately 10-11% of
      extrapulmonary TB involves joints and bones, which is approximately 1-3% of all
      TB cases. The global prevalence of latent joint and bone TB is approximately 19
      38 million.TB arthritis most commonly manifests as a monoarthritis of weight
      bearing joints in the hip or the knee. Oligo- or polyarticular presentation is
      not rare and may cause diagnostic confusion with inflammatory arthritis. Owing to
      the low incidence in developed countries, the diagnosis of joint and bone TB is
      often delayed. A high degree of sensitivity to this diagnosis would prevent
      delays, permitting prompt institution of anti-TB therapy and preventing
      irreversible joint damage. Despite advances, confirmation of diagnosis still
      relies on lengthy microbiological techniques or invasive biopsy. Due to the
      frequency of isoniazid resistance, initial treatment at present typically
      includes a combination of four drugs: isoniazid, rifampicin, pyrazinamide and
      streptomycin or ethambutol. Antimicrobial therapy should be of at least 9 months
      duration, longer in children and immunocompromised hosts. Surgical procedures
      should be restricted to joints with severe cartilage destruction, large
      abscesses, joint deformity, multiple drug resistance or atypical mycobacteria.

PMID- 12787532
TI  - Blood coagulation.
AB  - Blood coagulation can be initiated by two pathways: the extrinsic pathway, which
      is triggered by release of tissue factor from the site of injury, and the
      intrinsic system, which is stimulated by contact with a negatively charged
      surface. Following initial triggering, a series of serine proteases are
      sequentially activated, culminating in the formation of thrombin, the enzyme
      responsible for the conversion of soluble fibrinogen to the insoluble fibrin
      clot. Activation of coagulation is tightly regulated. Initiation by tissue factor
      is inhibited by tissue factor pathway inhibitor. Antithrombin can inactivate many
      of the serine proteases, including thrombin, by forming stable complexes which
      are rapidly cleared from the circulation. Protein C and protein S combine to
      inactivate coagulation factors V and VIII. The deposition of excess fibrin is
      prevented by the fibrinolytic system which can lyse fibrin into fibrin
      degradation products. Both genetic and environmental factors can influence the
      activation of coagulation and may predispose affected individuals to thrombosis.

PMID- 12787529
TI  - Infections and biological therapy in rheumatoid arthritis.
AB  - Infections are common in patients with rheumatic disorders. Reasons for such
      vulnerability include alterations of immunoregulation, disease severity,
      debility, co-morbid illnesses and the use of immunosuppressive medications. The
      advent of new biological agents has precipitated a further examination of the
      links between infection, the underlying disease and its treatment, resulting in
      several interesting observations. Interleukin-1 (IL-1) and tumour necrosis factor
      alpha (TNF-alpha), the major pro-inflammatory cytokines, play important roles in
      host defence against infection. Inhibition of their activity could therefore be
      anticipated to augment the risk of infection in patients with pre-existing
      abnormalities of immune regulation. Slight increases in the rates of infection
      were noted in the clinical trials of IL-1 receptor antagonist (IL-1Ra). In
      addition, a small number of opportunistic infections have been observed with the
      TNF inhibitor, etanercept. However, a marked increase in opportunistic infection,
      particularly tuberculosis, has occurred with the use of infliximab, an agent that
      also blocks TNF activity. The precise mechanisms by which these agents predispose
      to infection are currently being explored. The answers are likely to add
      significantly to our knowledge of how immune dysfunction contributes both to the
      pathophysiology of disease and the complications of therapy.

PMID- 12787533
TI  - Haemostasis in normal and abnormal pregnancy.
AB  - Haemostasis is a complex and dynamic equilibrium involving pro-coagulants, the
      natural anticoagulation system and fibrinolysis. Normal human pregnancy is
      associated with profound alterations to the process of haemostasis such that the
      pro-coagulant effect becomes dominant. There are very few studies which have
      attempted to elucidate the adaptations that take place in the uteroplacental
      circulation where the haemostatic system faces the conflicting tasks of
      maintaining blood fluidity during pregnancy while preparing for the haemostatic
      challenge of delivery. It is hypothesised that excessive thrombosis within the
      uteroplacental circulation provides the mechanistic basis for the reported
      associations between the inherited thrombophilias and major pregnancy
      complications. The evidence underpinning this widely quoted hypothesis is weak.

PMID- 12787534
TI  - The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation.
AB  - It is now possible to identify a predisposing thrombophilic condition for venous
      thrombosis in well over half of the cases. Certain thrombophilia diagnoses have a
      major impact on anticoagulant therapy, and hence it is incumbent upon physicians
      to understand how to diagnose and manage these conditions. This chapter covers
      the genetics and epidemiology of the inherited thrombophilias and provides a
      useful, common-sense approach to the laboratory evaluation of a patient with
      venous thrombosis.

PMID- 12787535
TI  - Inherited thrombophilia and venous thromboembolism.
AB  - Pulmonary thromboembolism (PTE) is the major cause of maternal death in the UK.
      Underlying PTE is the problem of deep venous thrombosis (DVT). Inherited
      thrombophilia will be found in about 50% of women with a personal history of
      venous thromboembolism (VTE), and screening for thrombophilia should be
      considered in women with a personal or family history of VTE. There is currently
      no place for universal screening for thrombophilia in pregnancy. There are
      particular considerations with regard to the management of thrombophilia in
      pregnancy. Low-molecular-weight heparins are now the heparin of choice in
      pregnancy because of a better side-effect profile (substantially reduced risk of
      heparin-induced osteoporosis and heparin-induced thrombocytopaenia) compared to
      unfractionated heparin, good safety record for mother and fetus and convenient
      once-daily dosing for prophylaxis.

PMID- 12787536
TI  - Inherited thrombophilia and poor pregnancy outcome.
AB  - Gestational vascular complications are a major cause of maternal and fetal
      morbidity.A growing body of evidence suggests a significant role for inherited
      thrombophilia in the development of gestational vascular complications. While the
      majority of women with thrombophilia will have an uneventful gestation, case
      control studies demonstrated that thrombophilia is more prevalent in cohorts of
      women with pregnancy loss and early-onset pre-eclampsia. Placental abruption and
      severe intrauterine growth restriction (IUGR) may also be associated with
      thrombophilia. Placental pathological findings in women with thrombophilia are
      hallmarked by thrombosis and fibrin deposition potentially to a greater degree
      than in normal pregnancy. Preliminary non-randomized studies suggest a benefit
      for prophylaxis with unfractionated and low-molecular-weight heparin (LMWH), and
      prospective randomized trials are in progress to define whether LMWH is effective
      in preventing pregnancy loss and other gestational vascular complications in
      women with thrombophilia and previous fetal wastage.

PMID- 12787537
TI  - Pre-eclampsia and thrombophilia.
AB  - Pre-eclampsia is a major cause of perinatal and maternal morbidity and mortality
      worldwide. Although knowledge of the precise aetiology remains uncertain a number
      of risk factors have been described. Thrombophilias have been associated with pre
      eclampsia in a number of studies and it is biologically plausible that they may
      contribute to the uteroplacental thrombosis that is frequently seen in pre
      eclampsia. If this association is confirmed, there is the potential to
      investigate preventive treatments, including low-molecular-weight heparins,
      aspirin and folate.

PMID- 12787538
TI  - Homocysteine and pregnancy.
AB  - Homocysteine is an amino acid that is involved in several key metabolic
      processes, including the methylation and sulphuration pathways. Blood
      concentrations of homocysteine are determined by various dietary factors,
      including folic acid and vitamin B(12), by alteration in physiology, such as
      renal impairment, and by variation in the activity of enzymes in the various
      pathways as a result of genetic polymorphisms, some of which are commonly found
      in the population. Hyperhomocysteinaemia has been associated with vascular
      disease, although whether it is cause or effect is still a matter of debate. In
      normal pregnancy, homocysteine concentrations fall. Disturbance of maternal and
      fetal homocysteine metabolism has been associated with fetal neural tube defects,
      with various conditions characterized by placental vasculopathy, such as pre
      eclampsia and abruption, and with recurrent pregnancy loss. Apart from folate
      supplementation, which has been clearly shown to halve the risk of fetal neural
      tube defects, no other strategies have been identified in relation to
      homocysteine metabolism that will reliably reduce the frequency of these other
      common obstetric pathologies.

PMID- 12787539
TI  - Inherited thrombophilias and anticoagulation in pregnancy.
AB  - Thromboprophylaxis, primary or secondary, should be considered in selected
      pregnant women with inherited thrombophilias; such women may be divided into high
      , medium- and low-risk categories on the basis of the specific thrombophilic
      defect and any personal or family history of venous thromboembolism (VTE). Women
      at high risk of VTE should receive treatment doses of low-molecular-weight
      heparin (LMWH) throughout pregnancy and should remain on anticoagulation for 6
      weeks postpartum, or, where appropriate, long-term. Women at moderate risk should
      be treated with prophylactic fixed-dose LMWH throughout pregnancy and for 6 weeks
      postpartum. Women at low risk should receive prophylactic fixed-dose LMWH for 6
      weeks postpartum, and low-dose aspirin LDA should be considered during pregnancy.
      LWMH offers important advantages over unfractionated heparin (UFH); heparin
      induced thrombocytopaenia (HIT) and osteopaenia are rarely seen. For treatment
      doses of LMWH, dosage adjustment based on anti-Xa levels is usually required as
      pregnancy progresses. Warfarin should be avoided throughout pregnancy. LMWH, UFH
      and warfarin are safe for breast-feeding mothers.

PMID- 12787540
TI  - Acquired thrombophilias and pregnancy.
AB  - Acquired thrombophilias are hypercoagulable states secondary to various
      aetiologies. In particular, during pregnancy the risks are exaggerated due to the
      underlying physiological changes. The commonest cause of acquired thrombophilia
      in pregnancy is antiphospholipid syndrome. Antiphospholipid syndrome (APS) is a
      complex multisystem disorder that has been associated with varied medical and
      obstetric complications. The pathogenesis of APS has been further elucidated in
      recent studies. The two most clinically significant antiphospholipid antibodies
      that are associated with recurrent pregnancy loss and thromboembolism are
      anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). The laboratory
      diagnosis is based on the presence of moderate to high positive aCL and/or LA
      antibodies. It is crucial that APS is not inappropriately diagnosed as this has
      implications for counselling and management with thromboprophylaxis during
      pregnancy. Over the last decade there have been significant changes in the
      laboratory and clinical criteria for the diagnosis of APS. National and
      international collaborations have made efforts to standardize the laboratory
      methods. There have been very few randomized placebo-controlled trials of drug
      therapy and so not all drug treatment strategies have a strong evidence base.
      With current management strategies, using low-molecular-weight heparin and
      aspirin, a greater than 70% live birth rate may be achieved in affected
      pregnancies. A multidisciplinary approach in the management of these women is
      vital.

PMID- 12787541
TI  - Thrombophilias and gynaecology.
AB  - In gynaecology, women are exposed to sex steroids when using oral contraceptives,
      hormone replacement therapy or when undergoing in vitro fertilization treatment
      and ovulation induction. Oral contraceptives and the use of hormone replacement
      therapy increase the risk of venous thrombosis. The risk is highest in the first
      year of use and higher among women with clotting defects. Women taking third
      generation oral contraceptives have an almost twofold increased risk of venous
      thrombosis compared with those taking second-generation oral contraceptives.
      Inherited clotting defects, which are themselves risk factors of venous
      thrombosis, (e.g. factor V Leiden mutation, deficiency of protein C, protein S or
      antithrombin, high plasma levels of factor VIII, and prothrombin mutation) appear
      synergistically increase the risk of venous thrombosis caused by oral
      contraceptives. Recent studies also point to an interaction between hormone
      replacement therapy and coagulation defects in causing venous thrombosis.
      Emerging studies show that in vitro fertilization treatment and ovulation
      induction are also risk factors for venous thrombosis; the role of coagulation
      defects in this association is not yet clear.

PMID- 12787546
TI  - Nutritional issues for adolescents.
AB  - This chapter provides background on the nutritional health of adolescents,
      focusing on a public health or population-level approach. We detail some specific
      nutritional issues and related health outcomes that are particularly relevant to
      adolescents, including overweight and obesity, type 2 diabetes, eating-related
      disorders and bone health as it relates to calcium intake. We discuss
      implications of the trends in adolescent dietary habits for practitioners and
      propose a research agenda for better understanding and positively influencing
      future adolescent nutritional health.

PMID- 12787547
TI  - Training modalities: over-reaching and over-training in athletes, including a
      study of the role of hormones.
AB  - BACKGROUND: An imbalance between the overall strain experienced during exercise
      training and the athlete's tolerance of such an effort may induce over-reaching
      (OR) or over-training syndrome (OTS). OR is characterized by an unexpected drop
      in performance despite increased training load or may lead to OTS, a complex
      state of exhaustion and persistent fatigue. AIM: As it is important to adapt
      training modalities to the athletes' needs, and as there is still a lack of
      objective parameters suitable for the prevention and diagnosis of OTS, we studied
      11 male elite cyclists, analysing the impact of training modalities ('training
      high-living low'; 'training low-living low') on exercise performance as well as
      on variable hormonal responses in order to detect early and sensitive markers for
      OR and/or OTS. RESULTS: Although the variable hormones varied quite substantially
      among the two training groups, two ratios--free testosterone/cortisol (FTCR) and
      insulin-like growth factor-I/cortisol (IGF-I/C)--did not differ at all. This is
      important because athletes' final aim is to improve in an anabolic way. In
      addition, IGF-binding protein 3 (IGF-BP3) might be a useful screening factor for
      OR and OTS. CONCLUSION: First, from a critical review of the existing over
      training research, it must be concluded that there has been little improvement in
      recent years in the tools available for the diagnosis of OTS. Second, as variable
      training modalities do have a major impact on isolated hormones in circulation,
      hormonal ratios such as FTCR and IGF-I/C have to be calculated. These ratios
      might be useful parameters in the early detection of a imbalance between anabolic
      and catabolic metabolism.

PMID- 12787548
TI  - Skeletal muscle as an artificial endocrine tissue.
AB  - Muscle has the ability to take up and express engineered genes and, because it is
      a post-mitotic tissue, their half-life of expression is prolonged. Although
      muscle is not regarded as a secretory tissue, in many cases, the gene products
      enter the systemic circulation. The possibility exists, therefore, of using this
      approach to alter levels of endocrine and paracrine factors. As a therapeutic
      procedure, this method has an advantage over the administration of the
      peptide/protein, which has a relatively short half-life and requires repeated
      injections. Engineered genes in plasmid or viral vectors under the control of a
      muscle-specific regulatory sequence may be introduced by intramuscular injection
      or by the introduction of transfected myoblasts. The latter is also being used in
      bioreactors to produce medicinal proteins/peptides in vitro as these offer some
      advantages over bacterial expression systems. However, for gene therapy purposes,
      there are still safety issues to be addressed.

PMID- 12787549
TI  - Androgens and the ageing male and female.
AB  - Androgens play a number of important physiological roles in the human. In the
      male, testosterone is required for virilization, normal sexual function, and both
      stimulation and maintenance of bone and muscle mass. Epidemiological studies have
      shown a progressive decline in testosterone levels with ageing in men. The
      clinical significance of this decline is still unclear, and there is controversy
      as to whether a specific syndrome of androgen deficiency or 'andropause' exists.
      The benefits of testosterone supplementation in this age group have yet to be
      equivocally established, and long-term safety data on testosterone administration
      in this setting are lacking. In the female, a decline in testosterone levels with
      ageing has been less clearly established due, at least in part, to the absence of
      sensitive assays. Available data suggest that the major role of testosterone
      replacement after menopause may be in those women who have had an oophorectomy.

PMID- 12787550
TI  - Herbal agents and over-the-counter medications in pregnancy.
AB  - Exposures to over-the-counter and herbal products are frequent in pregnant women.
      Limited information exists on the effects of many of these agents during
      pregnancy; it is not safe to assume that because these products are available
      without a prescription that they are without danger to the pregnant woman and her
      fetus. The basic principles utilized in deciding whether to employ prescription
      medications such as dose, embryological timing and potential toxic fetal effects
      also apply to herbal medications and over-the-counter agents. Conventional
      reasoning indicates that maternal exposure to poorly studied medications should
      be limited; therefore, many of these agents should be used sparingly or not at
      all by pregnant women. This chapter includes a review of selected herbal and over
      the-counter agents, including those which are considered to be acceptable for use
      in pregnancy.

PMID- 12787551
TI  - Phyto-oestrogens.
AB  - Phyto-oestrogens are oestrogenic compounds found in plants and consist of
      isoflavones, lignans and coumestans. Epidemiological studies provide evidence for
      a protective role of isoflavones, and to a lesser extent lignans, against the
      development of numerous chronic diseases, including several cancers,
      cardiovascular disease and osteoporosis. The structural similarity of phyto
      oestrogens to endogenous oestrogens has prompted the hypothesis that phyto
      oestrogens exert hormonal or anti-hormonal effects relevant to the risk of
      hormone-dependent disease and/or their suitability as a dietary alternative to
      hormone replacement therapy. The many human studies that have evaluated the
      effects of isoflavones and lignans on various endpoints relating to risk of
      various diseases have greatly increased knowledge of how these compounds behave.
      At the same time, additional questions have been generated. For example, the
      increasing interest in extracting isoflavones from the soybean for incorporation
      into dietary supplements has raised important concerns regarding safety and
      efficacy. Overall, it is clear that phyto-oestrogens are an area of active and
      advancing research with great potential to continue to affect human health.

PMID- 12787552
TI  - Melatonin: clinical relevance.
AB  - This chapter reviews the neural connections between the retinas and the pineal
      gland and summarizes the role of the light:dark cycle and the biological clock,
      i.e. the suprachiasmatic nuclei, in regulating pineal melatonin synthesis and
      secretion. The cellular mechanisms governing the nocturnal production of
      melatonin are described together with the way in which the misuse of light
      interferes with the circadian melatonin cycle and the total quantity of the
      indole generated. The chapter describes the nature of the membrane melatonin
      receptors and their signal transduction mechanisms in peripheral organs. The
      clinical implications and potential uses of melatonin in terms of influencing the
      biological clock (e.g. sleep and jet lag), immune function, and cancer initiation
      and growth are noted. Additionally, the chapter includes a description of the
      newly discovered free radical scavenging and antioxidant activities of melatonin;
      it also includes a list of clinical situations in which melatonin has been used
      with beneficial effects.

PMID- 12787553
TI  - HPA axis and memory.
AB  - The hormones of the hypothalamus-pituitary-adrenal (HPA) axis influence memory in
      situations of acute and chronic stress. The present review tries to summarize the
      current state of knowledge by describing the enhancing as well as the impairing
      effects of stress or glucocorticoid (GC) treatment documented in animals and
      humans. GCs secreted during the acquisition of a stressful task facilitate
      consolidation. However, acute stress (or GC treatment) unrelated to the task
      impairs performance. The effects of acute stress are additionally modulated by
      gender, age and the emotional valence of the learning material. Chronic stress in
      rodents has mostly impairing effects on memory and hippocampal integrity.
      However, other regions of the brain, such as the prefrontal cortex, are also
      sensitive to stress. In humans, similar observations have been reported in
      several patient populations as well as in older subjects. The potential to
      reverse these effects using behavioural or pharmacological approaches needs to be
      explored.

PMID- 12787557
TI  - The TNF superfamily.

PMID- 12787558
TI  - Biological functions of tumor necrosis factor cytokines and their receptors.
AB  - Tumor necrosis factor (TNF; formerly known as TNFalpha) and lymphotoxin
      (LT)alpha, originally characterized by their ability to induce tumor cell
      apoptosis and cachexia, are now considered as central mediators of a broad range
      of biological activities. These activities encompass beneficial effects for the
      host in inflammation and in protective immune responses against a variety of
      infectious pathogens. TNF family members on the other hand also exert host
      damaging effects in sepsis, in tumor cachexia as well as in autoimmune diseases.
      In addition, the essential roles of the core members of the TNF superfamily,
      LTalpha, LTbeta, TNF, and LIGHT as well as their receptors during the
      organogenesis of secondary lymphoid organs and the maintenance of the
      architecture of lymphatic tissues now becomes appreciated. The elucidation of the
      biological functions of these cytokines and their specific cell surface receptors
      has been crucially advanced by the study of gene-targeted mouse strains. This
      presentation summarizes the roles of TNFR and TNF-like cytokines in infection,
      sepsis and autoimmunity as well as the pivotal involvement of these molecules in
      the development of secondary lymphoid organs.

PMID- 12787559
TI  - The signaling adaptors and pathways activated by TNF superfamily.
AB  - Members of the TNF receptor superfamily play pivotal roles in numerous biological
      events in metazoan organisms. Ligand-mediated trimerization by corresponding homo
      or heterotrimeric ligands, the TNF family ligands, causes recruitment of several
      intracellular adaptors, which activate multiple signal transduction pathways.
      While recruitment of death domain (DD) containing adaptors such as Fas associated
      death domain (FADD) and TNFR associated DD (TRADD) can lead to the activation of
      a signal transduction pathway that induces apoptosis, recruitment of TRAF family
      proteins can lead to the activation of transcription factors such as, NF-kappaB
      and JNK thereby promoting cell survival and differentiation as well as immune and
      inflammatory responses. Individual TNF receptors are expressed in different cell
      types and have a range of affinities for various intracellular adaptors, which
      provide tremendous signaling and biological specificities. In addition, numerous
      signaling modulators are involved in regulating activities of signal transduction
      pathways downstream of receptors in this superfamily. Most of the TNF receptor
      superfamily members as well as many of their signaling mediators, have been
      uncovered in the last two decades. However, much remains unknown about how
      individual signal transduction pathways are regulated upon activation by any
      particular TNF receptor, under physiological conditions.

PMID- 12787560
TI  - Ectodysplasin signaling in development.
AB  - Ectodysplasin (Eda), a signaling molecule belonging to the tumor necrosis factor
      family, is required for normal development of several ectodermally derived organs
      in humans and mice. Two closely related isoforms of ectodysplasin, Eda-A1 and Eda
      A2, have been described which bind to and activate two different receptors, Edar
      and X-linked Eda-A2 receptor (Xedar), respectively. Mutations in Eda, Edar or
      other molecules of this signaling pathway cause ectodermal dysplasias
      characterized by defective development of teeth, hairs, and several exocrine
      glands such as sweat glands presumably due to impaired NF-kappaB response.
      Studies with mice either lacking the functional proteins of Edar pathway or
      overexpressing the ligand or receptor suggest that Eda-A1-Edar signaling has
      multiple roles in ectodermal organ development regulating their initiation,
      morphogenesis, and differentiation.

PMID- 12787561
TI  - Ten years on: mediation of cell death by the common neurotrophin receptor
      p75(NTR).
AB  - The common neurotrophin receptor p75(NTR) remains one of the most enigmatic of
      the tumor necrosis factor receptor (TNFR) superfamily: on the one hand, it
      displays a death domain and has been shown to be capable of mediating programmed
      cell death (PCD) upon ligand binding; on the other hand, its death domain is of
      type II (unlike that of Fas or TNFR I), and it has also been shown to be capable
      of mediating cell death in response to the withdrawal of ligand. Thus, p75(NTR)
      may function as a death receptor-similar to Fas or TNFR I-or a dependence
      receptor-similar to deleted in colorectal cancer (DCC) or uncoordinated gene-5
      homologues 1-3 (UNC5H1-3). Here, we review the data relating to the mediation of
      PCD by p75(NTR), and suggest that one reasonable model for the apparently
      paradoxical effects of p75(NTR) is that this receptor functions as a "quality
      control" in that it is capable of mediating PCD in at least four situations: (1).
      withdrawal of neurotrophins; (2). exposure to mismatched neurotrophins; (3).
      exposure to unprocessed neurotrophins; and (4). exposure of inappropriately
      immature cells to neurotrophins. Results to date suggest that these functions are
      mediated through different underlying mechanisms, and that their respective
      signaling pathways are cell type and co-receptor dependent.

PMID- 12787562
TI  - TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds
      the TweakR/Fn14 receptor.
AB  - The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) was
      initially described as a member of the tumor necrosis factor (TNF) superfamily in
      1997. TWEAK is a cell surface-associated type II transmembrane protein, but a
      smaller, biologically active form can also be shed into the extracellular milieu.
      There is one receptor currently known to bind TWEAK with physiological affinity,
      and it is a type I transmembrane protein that is referred to in the literature as
      either TWEAK receptor (TweakR) or fibroblast growth factor-inducible 14 (Fn14).
      TweakR/Fn14 is the smallest member of the TNF receptor (TNFR) superfamily
      described to date, and it appears to signal via recruitment of several different
      TNFR-associated factors. TWEAK has multiple biological activities, including
      stimulation of cell growth and angiogenesis, induction of inflammatory cytokines,
      and under some experimental conditions, stimulation of apoptosis. In this report,
      we summarize the results from recent studies focused on the TWEAK cytokine.
      Although these studies have contributed a significant amount of new information,
      numerous questions still remain regarding the role of TWEAK in both normal
      physiology and the pathogenesis of human disease.

PMID- 12787563
TI  - Biology of the TRANCE axis.
AB  - As the TNF and TNFR superfamilies have grown to more than two dozen combined
      members over the past 30 years, their involvement in interactions between immune
      cells, with regard to the events governing cellular differentiation, activation,
      and survival have been well established. The recently identified TNF superfamily
      cytokine, TRANCE (RANKL/OPGL/ODF/TNFSF11), which interacts with two receptors-one
      functional, TRANCE-R (RANK/TNFRSF11A), and one decoy, OPG (TNFRSF11B)-is a
      survival factor for activated dendritic cells, and may also be important for the
      maintenance of immune tolerance. TRANCE is also the key cytokine involved in
      osteoclast differentiation and activation, making TRANCE signaling crucial for
      proper bone homeostasis, and a potential therapeutic target in diseases such as
      osteoporosis, osteolytic metastatic cancer, arthritis, and periodontitis.
      Importantly, the positive role that TRANCE has in activating the immune system,
      appears to significantly contribute to pathologic bone loss. These observations
      have spurred intense study of the various ways in which the immune system can
      influence bone. Furthermore, TRANCE has also been demonstrated to play essential
      roles in the developmental processes leading to both lymph node formation, and
      the expansion and function of mammary glands during pregnancy and lactation.
      Thus, TRANCE is quickly emerging as a cytokine of significant importance to
      further understanding unique aspects of mammalian biology.

PMID- 12787564
TI  - Costimulation of T cells by OX40, 4-1BB, and CD27.
AB  - Costimulatory signals have been defined as signals brought about by ligation of
      membrane bound molecules that synergize with, or modify, signals provided when
      the T cell receptor engages peptide-MHC complexes. In large part, costimulatory
      signals are essential for many facets of a T cell response, and the general rule
      is that without these signals, a T cell is ineffective and may often succumb to
      death or become unresponsive. Until recently, costimulation has been dominated by
      studies of the Ig superfamily member, CD28, a constitutively expressed molecule
      that is required to initiate a majority of T cell responses. However, growing
      evidence over the past few years has now shown that several members of the TNFR
      family, OX40 (CD134), 4-1BB (CD137), and CD27, are equally important to the
      effective generation of many types of T cell response. In contrast to CD28, these
      molecules are either induced or highly upregulated on the T cell surface a number
      of hours or days after recognition of antigen, and appear to provide signals to
      allow continued cell division initially regulated by CD28 and/or to prevent
      excessive cell death several days into the response. An argument can be made that
      these molecules control the absolute number of effector T cells that are
      generated at the peak of the immune response and dictate the frequency of memory
      T cells that subsequently develop. The exact relationship between OX40, 4-1BB,
      and CD27, is at present unknown, including whether these molecules act together,
      or sequentially, or control differing types of T cell response. This review will
      focus on recent studies of these molecules and discuss their implications.

PMID- 12787565
TI  - The role of lymphotoxin in development and maintenance of secondary lymphoid
      tissues.
AB  - Secondary lymphoid organs provide the necessary microenvironment for the
      cooperation of antigen-specific T- and B-lymphocytes and antigen-presenting cells
      in order to initiate an efficient immune response. Remarkable progress in
      understanding of the mechanisms of lymphoid organogenesis was achieved due to the
      analysis of various gene-targeted mice. This review primarily focuses on the role
      of lymphotoxin (LT) in development, maturation and maintenance of secondary
      lymphoid organs.

PMID- 12787566
TI  - LIGHT-HVEM signaling and the regulation of T cell-mediated immunity.
AB  - LIGHT is a tumor necrosis factor (TNF) superfamily ligand that regulates T cell
      immune responses by signaling through the herpes virus entry mediator (HVEM) and
      the lymphotoxin beta receptor (LTbetaR). This review will present a summary of
      recent advances made regarding the immunobiology of the LIGHT-HVEM and LTbetaR
      systems. LIGHT has emerged as a potent initiator of T cell co-stimulation signals
      effecting CTL-mediated tumor rejection, allograft rejection and graft versus host
      disease. Constitutive expression of LIGHT leads to tissue destruction and
      autoimmune-like disease syndromes. In contrast to LTalphabeta, LIGHT plays a
      minimal role in lymphoid tissue development, yet some evidence indicates a role
      in negative selection in the thymus. These results provide an encouraging profile
      for the LIGHT-HVEM-LTbetaR axis as a potential target for controlling cellular
      immune reactions.

PMID- 12787567
TI  - The CD40-CD154 interaction in B cell-T cell liaisons.
AB  - The CD40 receptor is expressed constitutively on B lymphocytes, for which it
      provides important signals regulating clonal expansion, antibody production and
      isotype switching, as well as the development of humoral memory. The major source
      of CD154, the ligand for CD40, is activated T lymphocytes. Interactions between
      CD40 and CD154 provide a number of signals that play important roles in
      regulating the complex and multifactorial interactions between these two major
      cell types of the adaptive immune response. Understanding both the biological
      effects of this receptor-ligand interaction, as well as how CD40 signaling
      pathways are controlled, adds to our detailed picture of the complex interplay
      between B and T cells.

PMID- 12787568
TI  - The TNF family members BAFF and APRIL: the growing complexity.
AB  - B cell activating factor belonging to the TNF family (BAFF) and apoptosis
      inducing ligand (APRIL) are two related members of the TNF ligand superfamily.
      Although they share two receptors, TACI and BCMA, transgenic and knockout mice in
      this system reveal that their functions are not redundant. BAFF is a critical
      survival/maturation factor for peripheral B cells and this activity is mediated
      through a BAFF-specific receptor, BAFF-R. Overexpression of BAFF has been linked
      to autoimmune disease and aspects of B cell neoplasia. APRIL appears to play a
      role in T-independent type II antigen responses and T cell survival, but can also
      induce proliferation/survival of non-lymphoid cells. Elevated expression of APRIL
      has been found in some tumor cell lines and in tumor tissue libraries. Therapies
      designed to inhibit the BAFF and APRIL pathways holds great promise for the
      future.

PMID- 12787569
TI  - Biology of FasL.
AB  - FasL (CD95L) is a well-known and well-characterized death-inducing ligand.
      Spontaneous mutations in FasL and its cognate receptor Fas (CD95) have helped
      understand the role of these molecules in the disease. Once thought to be mainly
      involved in the homeostasis of immune system, the territory of FasL regulation
      has been expanded to angiogenesis and tumor progression. Here, we review what is
      currently known about the role of FasL in many areas of biology.

PMID- 12787570
TI  - Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy.
AB  - Apo2 ligand or tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (Apo2L/TRAIL) is one of several members of the TNF gene superfamily that induce
      apoptosis through engagement of death receptors. Apo2L/TRAIL is unusual as
      compared to any other cytokine as it interacts with a complex system of
      receptors: two pro-apoptotic death receptors and three anti-apoptotic decoys.
      This protein has generated tremendous excitement as a potential tumor-specific
      cancer therapeutic because, as a stable soluble trimer, it selectively induces
      apoptosis in many transformed cells but not in normal cells. Transcriptional
      activation of Apo2L/TRAIL by interferons (IFNs) through specific regulatory
      elements in its promoter, and possibly by a number of other cytokines, reveals
      its possible involvement in the activation of natural killer cells, cytotoxic T
      lymphocytes, and dendritic cells. In this review, we focus on the apoptosis
      signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date
      about the physiological role of this ligand and the potential for its application
      to cancer therapy.

PMID- 12787571
TI  - Viruses and the TNF-related cytokines, an evolving battle.
AB  - Tumor necrosis factor (TNF)-related cytokines are critical effector molecules in
      the immune response to viral pathogens. Engagement of the TNF receptors by their
      cognate ligands activates apoptotic and non-apoptotic signaling pathways, both of
      which can mediate antiviral activity. In response, viruses have evolved
      mechanisms to inhibit signaling by some cytokines of the TNF superfamily. These
      strategies are largely unique to each class of virus, but are similar in that
      they all target key regulatory checkpoints of the TNF pathway. In recent years,
      studies directed towards dissecting the mechanisms of TNF signaling and the viral
      retort have led to several significant discoveries, and form the basis for this
      review.

PMID- 12787572
TI  - In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian
      CNS.
AB  - Apoptosis has been recognized to be an essential process during neural
      development. It is generally assumed that about half of the neurons produced
      during neurogenesis die before completion of the central nervous system (CNS)
      maturation, and this process affects nearly all classes of neurons. In this
      review, we discuss the experimental data in vivo on naturally occurring neuronal
      death in normal, transgenic and mutant animals, with special attention to the
      cerebellum as a study model. The emerging picture is that of a dual wave of
      apoptotic cell death affecting central neurons at different stages of their life.
      The first wave consists of an early neuronal death of proliferating precursors
      and young postmitotic neuroblasts, and appears to be closely linked to cell cycle
      regulation. The second wave affects postmitotic neurons at later stages, and is
      much better understood in functional terms, mainly on the basis of the
      neurotrophic concept in its broader definition. The molecular machinery of late
      apoptotic death of postmitotic neurons more commonly follows the mitochondrial
      pathway of intracellular signal transduction, but the death receptor pathway may
      also be involved.Undoubtedly, analysis of naturally occurring neuronal death
      (NOND) in vivo will offer a basis for parallel and future studies aiming to
      elucidate the mechanisms of pathologic neuronal loss occurring as the result of
      conditions such as neurodegenerative disorders, trauma or ischemia.

PMID- 12787573
TI  - Adenosine in the spinal cord and periphery: release and regulation of pain.
AB  - In the central nervous system (CNS), adenosine is an important neuromodulator and
      regulates neuronal and non-neuronal cellular function (e.g. microglia) by actions
      on extracellular adenosine A(1), A(2A), A(2B) and A(3) receptors. Extracellular
      levels of adenosine are regulated by synthesis, metabolism, release and uptake of
      adenosine. Adenosine also regulates pain transmission in the spinal cord and in
      the periphery, and a number of agents can alter the extracellular availability of
      adenosine and subsequently modulate pain transmission, particularly by activation
      of adenosine A(1) receptors. The use of capsaicin (which activates receptors
      selectively expressed on C-fibre afferent neurons and produces neurotoxic actions
      in certain paradigms) allows for an interpretation of C-fibre involvement in such
      processes. In the spinal cord, adenosine availability/release is enhanced by
      depolarization (K(+), capsaicin, substance P, N-methyl-D-aspartate (NMDA)), by
      inhibition of metabolism or uptake (inhibitors of adenosine kinase (AK),
      adenosine deaminase (AD), equilibrative transporters), and by receptor-operated
      mechanisms (opioids, 5-hydroxytryptamine (5-HT), noradrenaline (NA)). Some of
      these agents release adenosine via an equilibrative transporter indicating
      production of adenosine inside the cell (K(+), morphine), while others release
      nucleotide which is converted extracellularly to adenosine by ecto-5'
      nucleotidase (capsaicin, 5-HT). Release can be capsaicin-sensitive, Ca(2+)
      dependent and involve G-proteins, and this suggests that within C-fibres, Ca(2+)
      dependent intracellular processes regulate production and release of adenosine.
      In the periphery, adenosine is released from both neuronal and non-neuronal
      sources. Neuronal release from capsaicin-sensitive afferents is induced by
      glutamate and by neurogenic inflammation (capsaicin, low concentration of
      formalin), while that from sympathetic postganglionic neurons (probably as
      adenosine 5'-triphosphate (ATP) with NA) occurs following more generalized
      inflammation. Such release is modified differentially by inhibitors of AK and AD.
      Following nerve injury, there is an alteration in capsaicin-sensitive adenosine
      release, as spinal release now is less responsive to opioids, while peripheral
      release is less responsive to inhibitors of metabolism. Following inflammation,
      adenosine is released from a variety of cell types in addition to neurons (e.g.
      endothelial cells, neutrophils, mast cells, fibroblasts). ATP is released both
      spinally and peripherally following inflammation or injury, and may be converted
      to adenosine by ecto-5'-nucleotidase contributing an additional source of
      adenosine. Release of adenosine from both spinal and peripheral compartments has
      inhibitory effects on pain transmission, as methylxanthine adenosine receptor
      antagonists reduce analgesia produced by agents which augment extracellular
      levels of adenosine spinally (morphine, 5-HT, substance P, AK inhibitors) and
      peripherally (AK inhibitors, AD inhibitors). Increases in extracellular adenosine
      availability also may contribute to antiinflammatory effects of certain agents
      (methotrexate, sulfasalazine, salicylates, AK inhibitors), and this could have
      secondary effects on pain signalling in chronic inflammation. The purpose of the
      present review is to consider: (a). the factors that regulate the extracellular
      availability of adenosine in the spinal cord and at peripheral sites; and (b).
      the extent to which this adenosine affects pain signalling in these two distinct
      compartments.

PMID- 12787574
TI  - Neurotrophin secretion: current facts and future prospects.
AB  - The proteins of the mammalian neurotrophin family (nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin
      4/5 (NT-4/5)) were originally identified as neuronal survival factors. During the
      last decade, evidence has accumulated implicating them (especially BDNF) in
      addition in the regulation of synaptic transmission and synaptogenesis in the
      CNS. However, a detailed understanding of the secretion of neurotrophins from
      neurons is required to delineate their role in regulating synaptic function. Some
      crucial questions that need to be addressed include the sites of neurotrophin
      secretion (i.e. axonal versus dendritic; synaptic versus extrasynaptic) and the
      neuronal and synaptic activity patterns that trigger the release of
      neurotrophins. In this article, we review the current knowledge in the field of
      neurotrophin secretion, focussing on activity-dependent synaptic release of BDNF.
      The modality and the site of neurotrophin secretion are dependent on the
      processing and subsequent targeting of the neurotrophin precursor molecules.
      Therefore, the available data regarding formation and trafficking of
      neurotrophins in the secreting neurons are critically reviewed. In addition, we
      discuss existing evidence that the characteristics of neurotrophin secretion are
      similar (but not identical) to those of other neuropeptides. Finally, since BDNF
      has been proposed to play a critical role as an intercellular synaptic messenger
      in long-term potentiation (LTP) in the hippocampus, we try to reconcile this
      possible role of BDNF in LTP with the recently described features of synaptic
      BDNF secretion.

PMID- 12787575
TI  - Off-shore activity and environmental compatibility in the Mediterranean.

PMID- 12787577
TI  - Black Sea seagrasses.

PMID- 12787576
TI  - The role of the exchanges through the Strait of Gibraltar on the budget of
      elements in the Western Mediterranean Sea: consequences of human-induced
      modifications.
AB  - The role of the Strait of Gibraltar on the exchanges of substances between
      Mediterranean Sea and the Atlantic Ocean is reviewed. The previous estimations
      have been recalculated by using a similar water flux and compared with the river
      and atmospheric inputs to the Western Mediterranean Sea. The man-induced changes
      in the dimensions of the Strait of Gibraltar increasing (planning the sill) or
      reducing of the cross-section by a total or partial dam are discussed. A total
      dam will control the sea-level rise in the Mediterranean Sea, but an annual
      increase of major nutrient concentrations of 1-2% could be expected, lower than
      the rate of increase of the river and atmospheric inputs in the Western
      Mediterranean Sea. The increase of the cross-section of the Strait by increasing
      the depth (planning) at the sill could compensate the increase of the external
      nutrient inputs.

PMID- 12787578
TI  - How multiagency partnerships can successfully address large-scale pollution
      problems: a Hawaii case study.
AB  - Oceanic circulation patterns deposit significant amounts of marine pollution,
      including derelict fishing gear from North Pacific Ocean fisheries, in the
      Hawaiian Archipelago [Mar. Pollut. Bull. 42(12) (2001) 1301]. Management
      responsibility for these islands and their associated natural resources is shared
      by several government authorities. Non-governmental organizations (NGOs) and
      private industry also have interests in the archipelago. Since the marine debris
      problem in this region is too large for any single agency to manage, a
      multiagency marine debris working group (group) was established in 1998 to
      improve marine debris mitigation in Hawaii. To date, 16 federal, state, and local
      agencies, working with industry and NGOs, have removed 195 tons of derelict
      fishing gear from the Northwestern Hawaiian Islands. This review details the
      evolution of the partnership, notes its challenges and rewards, and advocates its
      continued use as an effective resource management tool.

PMID- 12787579
TI  - Transfer of organic contaminants to the Baltic in the Odra Estuary.
AB  - This paper describes the transfer of organic contaminants to the sea, using PAHs
      (12 compounds) and PCBs (11 congeners) as examples, through a eutrophicated
      coastal lagoon (Szczecin Lagoon, on the Polish-German border). The transfer of
      contaminants study was based on their concentration in recent sediments (0-10
      cm), in relation to different environmental conditions such as temperature,
      salinity, turbidity, oxygen and nutrients in water, hydrological conditions,
      organic carbon and biomarkers (pigments and their derivatives) in sediments.
      Results include the data obtained between 1994 and 2000, also those on before and
      afterwards the great flood in July 1997, at different stations in the Lagoon and
      the adjacent Pomeranian Bay. The results indicated that the eutrophic estuary of
      the shape of lagoon acts as an effective trap for the hydrophobic organic
      pollutants. The abundance and taxonomy of plankton as well as detritus derived
      from it play an important role in bonding the studied compounds. The salinity
      gradient in the lagoon has a significant influence upon deposition of the
      pollutants from the water column to the sediments and the residence time of the
      compounds there depends strongly on oxic-anoxic status of the sediments and the
      strength of interaction with sediments resulting from polarity, the type and
      stability of associates formed, as well as on hydrological conditions. We
      conclude that eutrophication in this area prevents pollution of the sea to some
      extent.

PMID- 12787580
TI  - Dissolved trace metal distributions in Port Jackson estuary (Sydney Harbour),
      Australia.
AB  - Concentrations of dissolved metals (Cd, Cu, Ni, Mn and Zn) were determined for
      summer and winter, under low-flow conditions in Port Jackson, a microtidal, well
      mixed estuary in south-east Australia. Mean concentrations of Cd (0.04+/-0.02
      microg/l), Ni (0.86+/-0.40 microg/l), Mn (20.0+/-25 microg/l) and Zn (6.47+/-2.0
      microg/l) were below water quality guidelines. Concentrations of Cu (1.68+/-0.37
      microg/l), however, slightly exceeded recommended values. Dissolved Ni and Mn
      behaved mostly conservatively, whereas Cd, Cu and Zn showed mid-estuarine maxima.
      Peaks in Cd, Cu and Zn concentrations were located in the upper estuary,
      independent of the salinity and suspended particulate matter loading, and were
      consistent with anthropogenic inputs of metals in the estuary. Concentrations of
      dissolved Cu were highest in summer, whereas concentrations of Cd, Ni and Mn were
      significantly lower in summer than winter (P< or =0.05). The increase in
      temperature and biological activity during summer explained the seasonal
      variation. The sequence of log K(d) values (20-30 salinity) was Mn>Zn>Cu>Ni.
      These results give unique information concerning the contemporaneous distribution
      of dissolved trace metals in the Port Jackson estuary and they provide a data set
      against which the long-term contamination may be assessed.

PMID- 12787581
TI  - Comparing methods and sediment contaminant indicators for determining produced
      water fate in a Louisiana estuary.
AB  - Produced water is a high salinity by-product resulting from oil and gas
      production. Disposal methods include surface water discharge. The current field
      method used to determine its fate in estuarine systems involves extending a
      compass oriented transect (COT) from the point source discharge--a method
      designed for a uniformly dispersing effluent discharged into a uniform offshore
      environment that may be inappropriate for the hydrologic and geomorphologic
      complexities found in estuarine systems. Prior research established the viability
      of the salinity stratification transect (SST) method. Both COT and SST methods
      were used in a small open bay to determine which more accurately detected
      effluent dispersion. Determination was based on sediment contaminant indicators
      (SCIs), including interstitial salinity, hydrocarbons, metals, and radium
      concentrations. Additionally, SCIs were evaluated for their ability to serve as
      indicators of effluent dispersion. The data revealed that SST stations exhibited
      higher contaminant concentrations and that this approach was more accurate in
      tracking the produced water plume. The data also suggested that SCIs varied in
      their ability to serve as indicators. Good indicators included interstitial
      salinity, total targeted aromatic hydrocarbons substantiated with a modified
      fossil fuel pollution index value, certain metals, and radium-228.

PMID- 12787583
TI  - Application of enterococci antibiotic resistance patterns for contamination
      source identification at Huntington Beach, California.
AB  - Huntington Beach, California, one of the most popular surfing spots in the world,
      is plagued by sporadic, elevated levels of fecal bacteria. To assist with
      pollution source identification, we analyzed antibiotic resistance patterns
      (ARPs) of enterococci from four known sources (bird feces, urban runoff, coastal
      marsh sediment and sewage effluent from local sanitation district) and one
      unknown source (seawater) using seven antibiotics at four concentrations each. Of
      2491 enterococci tested, all were resistant to at least one antibiotic at some
      level. Discriminant analysis indicated that the average correct classification
      rates for bird feces and urban runoff sources were above 80%. Sewage effluent
      contained mixed fecal sources. Sixty-four percent of the sewage isolates
      classified with the sewage category, while the other 35% of isolates were
      assigned evenly across the other three categories. When enterococci isolated from
      the seawater were classified using the known ARP database, it was evident that
      bird feces were the source of surf zone contamination on some days while the
      coastal salt marsh and sewage plume may have impacted the surf zone water quality
      to various degrees during other times.

PMID- 12787582
TI  - Contamination by organochlorine compounds in sturgeons from Caspian Sea during
      2001 and 2002.
AB  - Organochlorine compounds (OCs) were determined in the five species of sturgeons
      collected from coastal waters of Caspian Sea in Kazakhstan, Azerbaijan,
      Turkmenistan and Iran during 2001 and 2002 to understand their status of
      contamination and accumulation features. Among OCs examined, concentrations of
      DDTs (DDT and its metabolites) were predominant in all the sturgeon samples with
      concentrations ranging from 73 to 31,000 ng/g on lipid weight basis, followed by
      PCBs, CHLs, HCHs, HCB, dieldrin, TCPMOH, and heptachlor epoxide in order. The
      concentrations of OCs in beluga (Huso huso) were the highest among all the five
      species. When comparing residue levels among same species, OC residues were
      highest in sturgeons from Azerbaijan and Kazakhstan and lowest in Turkmenistan.
      However, the concentrations of HCHs, dieldrin, and heptachlor epoxide in
      sturgeons showed less geographical variability.

PMID- 12787584
TI  - Selection of bioindicators for monitoring marine environmental quality in the Bay
      of Fundy, Atlantic Canada.
AB  - Distribution of metals, PAH's and PCB's in lobsters, mussels, and sediments were
      used to assess marine environmental quality of the Bay of Fundy. This study
      demonstrates that the lobster (Homarus americanus) is a better bioindicator for
      monitoring contaminants in the marine environment and has a greater capacity for
      the uptake and accumulation of contaminants than the mussel (Mytilus edulis) and
      sediments. A definite pattern in the spatial distribution of lobster Cu, Cd, and
      Ag was evident. The distribution of organic contaminants for both mussels and
      lobsters in the Bay of Fundy lacked a spatial trend, and organic contaminants
      were undetectable in sediments from all sites. The Gulf Watch Programme, which
      monitors chemicals in mussels in the Bay of Fundy, did not indicate a problem
      with high levels of Cu, Cd, and Zn in the ecosystem. Analytes below the detection
      limit, such as in mussels and sediments, increase the difficulties of chemical
      analysis and detection for environmental monitoring. Deficiencies of mussels in
      monitoring the Bay of Fundy were discussed.

PMID- 12787585
TI  - Measurement of copper release rates from antifouling paint under laboratory and
      in situ conditions: implications for loading estimation to marine water bodies.
AB  - The release of biocides, such as copper (Cu), from antifouling (AF) coatings on
      vessel hulls represents a significant proportion of overall Cu loading in those
      harbors and estuaries where substantial numbers of small craft or large vessels
      are berthed. Copper release rates were measured on several self-polishing, tin
      free coatings and an ablative Cu reference coating applied to steel panels using
      three measurement methods. The panels were exposed in natural seawater in San
      Diego Bay, and release rates were measured both in the laboratory and field over
      2 years. Results with the static (20 cm x 30 cm) panels indicated that Cu release
      rates were initially high (25-65 microg Cu cm(-2)day(-1)), with a large range of
      values between paint types. Release rates declined to substantially lower rates
      (8-22 microg cm(-2)day(-1)) with reduced variability within 2 months. Release
      rates continued to decrease over time for approximately 6 months when relatively
      constant release rates were observed for most coatings. Over time, relative
      differences in Cu release rates measured by three exposure methods decreased,
      with all coatings exhibiting similar behavior toward the end of the study. Lowest
      overall Cu release rates were observed with the self-polishing experimental paint
      no. 7 in static-dynamic and in situ treatments. The highest periodic release
      rates were measured from panels that experienced periods of both static and
      dynamic exposure (8.7 ms(-1) rotation). The lowest release rates were measured
      from panels that experienced static, constant depth exposure, and where release
      rates were evaluated in situ, using a novel diver-deployed measurement system.
      Results from this in situ technique suggests that it more closely reflects actual
      Cu release rates on vessel hulls measured with intact natural biofilms under
      ambient conditions than measurements using standardized laboratory release rate
      methods. In situ measurements made directly on the AF surface of vessels
      demonstrated typically lower release rates than from the panel studies, averaging
      8.2 microg cm(-2)day(-1) on pleasure craft, and 3.8 microg cm(-2)day(-1) on Navy
      vessels. The data suggest that the presence of an established biofilm likely
      serves to moderate the release of Cu from field-exposed antifouling coatings both
      on panels and hull surfaces.

PMID- 12787586
TI  - Evaluation of nonwoven polypropylene oil sorbents in marine oil-spill recovery.
AB  - Mechanical recovery of oil by oil sorbents is one of the most important
      countermeasures in marine oil-spill response. Polypropylene is the ideal material
      for marine oil-spill recovery due to its low density, low water uptake and
      excellent physical and chemical resistance. Different forms of polypropylene
      nonwoven sorbents were evaluated in this study in terms of initial oil-sorption
      capacities and oil-retention properties. The investigation revealed that the
      fibre diameter, sorbent porosity and oil property are the most important factors
      in the oil-sorption performance of polypropylene nonwoven sorbents.

PMID- 12787587
TI  - Heavy metal contamination in sediment and biomonitors from sites around the Isle
      of Man.

PMID- 12787588
TI  - Increased risk of non-seasonal and body immersion recreational marine bathers
      contacting indicator microorganisms of sewage pollution.

PMID- 12787589
TI  - Toward coastal zone management that ensures coexistence between people and nature
      in the 21st century.

PMID- 12787590
TI  - Assay of phosphatase activity and ATP biomass in tideland sediments and
      classification of the intertidal area using chemical values.
AB  - Detailed studies of the phosphatase activity in the tidelands were examined
      including the localization of the phosphatase activities and the spatial
      distributions of the activity in the tidelands around Hiroshima Bay, the Aki
      Bingo Open Sea and Isahaya Bay of Kyushu on the western side of Japan. The
      results indicate that the phosphatase activity of the sediment fraction accounts
      for 98% of the tideland activity. Furthermore, we classified 19 tidelands into
      four groups by a cluster analysis using two parameters: phosphatase activities
      and ATP (adenosine 5(')-triphosphate) biomass. The first group is a member of the
      tidelands located in areas remote from the cities. They have a low phosphatase
      activity and low ATP biomass and the seawater in the tideland is very clean. The
      second is a group with a low phosphatase activity and high ATP biomass. In the
      tidelands belonging to this group, large numbers of benthos and shellfish can be
      observed. The third group has a high phosphatase activity and a relatively low
      ATP biomass. The estuary tidelands located near Hiroshima City belong to the
      third group. The last one is tidelands with a high phosphatase activity and high
      ATP biomass. In this group, the ratio of the phosphatase activity to ATP biomass
      is relatively low. In the summer, we observed deterioration in the water quality
      and accumulation of sludge on the sea bottom in the tideland of the last
      group.Moreover, we employed a multiple regression analysis and proposed an
      equation to obtain the group number of the cluster analysis using the assayed
      values of the phosphatase activity and the ATP biomass.

PMID- 12787591
TI  - The influence of environmental variability on silicate exchange rates between
      sediment and water in a shallow-water coastal ecosystem, the Seto Inland Sea,
      Japan.
AB  - Silicate regeneration was determined in a shallow-water coastal ecosystem (Shido
      Bay, the Seto Inland Sea, Japan) during 1999-2000. The present study was carried
      out directly by core incubation and by determining gradients of dissolved
      silicate (DSi) in the pore water. Incubated fluxes ranged from 25.5 to 132.6
      mgSim(-2)d(-1), and were 1.6-21.6 times greater than diffusive fluxes (5.4-43.3
      mgSim(-2)d(-1)). The disparity between fluxes measured by core incubation and
      modeling pore water indicated that other physical, chemical or biological
      processes, in addition to diffusion of DSi from below, contribute to DSi fluxes
      measured during the incubation of undisturbed cores. A regression analysis
      revealed that water temperature and salinity explained 24% and 23%, respectively,
      of season to season variability in incubated fluxes. Microphytobenthos was
      responsible for 37% of the variability in measured rate of DSi fluxes, with
      greatly reducing DSi release rates due to their own DSi demand. Moreover, the
      inverse relationship between the DSi fluxes and biogenic silica (Bio-Si)
      concentrations in the surface sediment, suggested that about 41% of the
      variability in the DSi fluxes were explained by Bio-Si concentrations in the
      surface sediment. As a result, Shido Bay showed silicate regeneration of
      incubated cores to be a consequence of Bio-Si dissolution depending on
      microphytobenthos, temperature and salinity, while diffusive fluxes appeared to
      be limited by DSi in the pore water. An annual average of DSi flux (68.7+/-32.9
      mgSim(-2)d(-1)) from the sediments to the water column corresponds to 38% of DSi,
      required for primary production by phytoplankton in Shido Bay.

PMID- 12787592
TI  - Estimation of particulate organic carbon flux in relation to photosynthetic
      production in a shallow coastal area in the Seto Inland Sea.
AB  - Sediment trap experiments were carried out three times from 1999 to 2000, in the
      western part of the Seto Inland Sea (Suo-Sound), Japan. We investigated both the
      particulate flux and the composition of chemical substances in the sediment trap
      samples. Based on the results, we discuss the origin of particulate organic
      carbon (POC) collected by the sediment traps in a coastal area. Moreover, we
      purposed to estimate the flux of the portion of the POC that is derived from
      phytoplankton photosynthesis. The fluxes of POC varied between 677 and 3424 mgC
      m(-2) d(-1). Significant positive correlations between POC and aluminum (Al)
      fluxes suggested that these components show almost the same behaviour. The mean
      value of the Al flux was about eight times higher than that of Al burial rates on
      the sediment surface. Therefore, it seems that the POC flux observed with the
      sediment traps was considerably overestimated. Moreover, judging from the fact
      that Al is a typical terriginous element, it seems that most of the POC collected
      in the sediment traps derived from the re-suspended surface sediment or sediment
      transported laterally from shallow flanks such as intertidal mudflats. The fluxes
      of chlorophyll a (Chl a) were independent of the POC fluxes, and a relatively
      consistent correlation was found between Chl a abundance in the water column and
      the Chl a flux. Moreover, surface sediment Chl a content was approximately 100
      times lower than that of suspended matter. Therefore, resuspension and
      terriginous contributions to Chl a collected in sediment traps are likely to be
      negligible. The POC content in the trap samples varied between 22.4 and 70.7 mg
      g(-1) dry weight. The variations of POC contents were positively correlated with
      the Chl a contents: POC(mg g(-1))=76.5 x Chl a(mg g(-1)) + 26.0 (r=0.95, p<0.01,
      n=9). This result shows that POC contents strongly corresponded with
      phytoplankton and their debris. It was also considered that the fraction of POC
      derived from phytoplankton primary production could be estimated as Chl a content
      times a certain factor. In this study, we estimated the flux of the portion of
      the POC originating from phytoplankton production by multiplying the Chl a fluxes
      by 76.5 (the mean POC:Chl a ratio in the trap samples). These values varied
      between 308 and 758 mgC m(-2) d(-1), and accounted for 35.1+/-21.2% of total POC
      flux. Although the amount of POC that originates from phytoplankton
      photosynthesis was a small portion of total POC flux, it seems to be a large
      portion of potential primary production in the water column.

PMID- 12787593
TI  - A model of fish preference and mortality under hypoxic water in the coastal
      environment.
AB  - Eutrophication and associated occurrence of hypoxic condition could cause
      significant damage to marine ecosystems, resulting in considerable economic
      losses to fisheries and aquaculture and is a major source of stress that fish
      often have to contend with in order to survive. This problem is likely to be
      exacerbated in the coming years, since the wastewater treatment facilities is
      unlikely to catch up with increasing human activities. Moreover, large-scale
      reclamation projects in coastal areas have recently been increased, and these
      activities certainly have adverse impacts on water quality and fisheries
      resources. Coastal construction has a significant role in the development of
      hypoxic water by changing the current and mixing pattern of water. Changes in
      species composition and decreases in species richness and diversity have been
      well documented in hypoxic systems. Hypoxia could cause endocrine disruption in
      fish and eliminate populations of sensitive species. Shallow coastal areas are of
      great importance for the special nursery of fish and shellfish and land
      reclamation in these areas cause strong damage to fisheries. Although the
      tolerance of aquatic life to hypoxia is known, there is no information about the
      mortality of fish caused by hypoxia because fish can swim around it and no
      modeling study has yet been carried out. Criteria that influence the movement of
      fish are: amounts of food, water temperature and depth, dissolved oxygen
      concentration and nature of seabed. However, among these, water temperature and
      dissolved oxygen are the most crucial parameters that affect survival, movement
      and growth of fish. In this paper, a model of fish preference and mortality for
      environmental conditions was developed and applied to the Hakata Bay where
      hypoxic water occurs every summer. For the purpose of this study, a field survey
      of fish behavior under hypoxic water was conducted by releasing marbled sale
      (Pleuronectes yokohamae) in the inner bay. Moreover, a series of preference tests
      for DO, salinity and temperature in the laboratory were conducted in order to
      decide preference parameters of fish. Using the results of both field and
      laboratory studies, a sub-module of fish preference and mortality was coded
      within an integrated hydrothermal and eutrophication model (CHEM) to predict the
      behavior and mortality of marbled sale when hypoxia would occur in the bay. The
      model could reasonably simulate the behavior of the fish under hypoxia. An
      assessment of the impact of the ongoing land reclamation project of about 401 ha
      in the Wajiro tidal flat zones at the head of the bay on the fisheries resources
      was also conducted using the model. The results showed that the artificial land
      lowered the mortality rate of fish under hypoxic condition in the bay during the
      summer period.

PMID- 12787594
TI  - The characteristics of nutrients and eutrophication in the Pearl River estuary,
      South China.
AB  - In the spring of 1998, 24-h time series and synchronization of vertical profiles
      of NO(3)-N, NO(2)-N, NH(3)-N, PO(4)-P, chlorophyll a, suspended substance,
      salinity, temperature and other chemical parameters were taken at 10 stations in
      the Pearl River estuary in order to analyze the status and characteristics of
      nutrients and eutrophication. The results indicated that dissolved inorganic
      nitrogen (DIN) mainly came from the four river channels in the main estuary, and
      NO(3)-N was the main form of DIN in most area. The concentration of DIN was
      general above 0.30 mg l(-1) in the estuary, and more than 0.50 mgl(-1) in most
      part. Phosphate from four river channels was not the main sources, but land-based
      sources from the area near Shenzhen Bay or along the estuary were obvious, and
      other land-based sources outside the estuary brought by coastal current and flood
      tide current were also the main contributions. The concentration of phosphate was
      generally about 0.015 mg l(-1) except the area near Shenzhen Bay. The ratio of
      N:P was generally high, and it was higher in the north than in the south. The
      highest ratio was higher than 300, and the lowest one was over 30. The
      concentration of chlorophyll a was about 0.8-7.8 mg m(-3), and turbidity and
      phosphate may be the main two limiting factors for algal bloom in the estuary.
      The concentration of nutrients decreased slightly in the past decade, but still
      stayed at a high level. The nutrients mainly came from domestic sewage,
      industrial wastewater, agriculture fertilizer and marine culture in the Pearl
      River estuary.

PMID- 12787595
TI  - The Seto Inland Sea--eutrophic or oligotrophic?
AB  - The present water quality conditions in the Seto Inland Sea of Japan are
      described along with an historical background before and after the measures taken
      to reduce eutrophication. The directive to reduce phosphorus discharge into this
      area was very effective, reducing the number of red tides from about 300 cases
      per year at their peak in 1976 to the recent level of about 100 cases per year,
      indicating the improvement of seawater quality. However, the hastiness of the
      measures taken to reduce phosphorous seems to have led to a depletion of
      dissolved inorganic phosphorus that is an essential nutrient for the growth of
      phytoplankton. Fishery production has also decreased with the reduction of
      phosphorus, showing a time lag, and the relationship between them shows a
      hysteresis-like pattern indicating that the condition of fishery production is
      currently in a critical stage of collapse. This implies that the phosphorus
      reduction could have lowered the phytoplankton primary production and also caused
      a detrimental effect on the fishery production. Noteworthy is the change in the
      phytoplankton species composition. The dominant species that form red tides have
      changed from non-harmful diatoms to harmful raphidophytes in the eutrophication
      process and then finally to harmful/toxic dinoflagellates in the
      oligotrophication process. This indicates that the measures to reduce phosphorus
      have caused a change in phytoplankton species composition, thereby altering the
      food web structure, suggesting that this might be the major cause of the
      reduction of fishery production. In conclusion, the Seto Inland Sea of Japan is
      apparently in an oligotrophic condition, and it could be said to be in the state
      of "cultural oligotrophication" caused by the hasty reduction of phosphorus
      loading. Dam construction, as another possible cause of the cultural
      oligotrophication, is also discussed, and evidence relating to the existence of
      numerous dams in this area is also shown. Stress is placed on the regulation of
      the level of nutrients and their elemental ratio in the seawater, because these
      factors are considered to be effective in preventing the generation of harmful
      algae and in sustaining the fishery production through preservation of the
      natural environment. A proposal is also described regarding how these factors
      could be controlled.

PMID- 12787596
TI  - Water pollution and habitat degradation in the Gulf of Thailand.
AB  - The Gulf of Thailand has been a major marine resource for Thai people for a long
      time. However, recent industrialization and community development have exerted
      considerable stress on the marine environments and provoked habitat degradation.
      The following pollution problems in the Gulf have been prioritized and are
      discussed in details: (1) Untreated municipal and industrial waste water are
      considered to be the most serious problems of the country due to limited waste
      water treatment facilities in the area. (2) Eutrophication is an emerging problem
      in the gulf of Thailand. Fortunately, the major species of phytoplankton that
      have been reported as the cause of red tide phenomena were non-toxic species such
      as Noctiluca sp. and Trichodesmium sp. (3) Few problems have been documented from
      trace metals contamination in the Gulf of Thailand and public health threat from
      seafood contamination does not appear to be significant yet. (4) Petroleum
      hydrocarbon residue contamination is not a problem, although a few spills from
      small oil tankers have been recorded. A rapid decrease in mangrove forest, coral
      reefs, and fisheries resources due to mismanagement is also discussed.

PMID- 12787597
TI  - Total dissolved and particulate lead in the Western Harbor of Alexandria, a
      Mediterranean basin under stress.
AB  - The Western Harbor of Alexandria, the largest harbor of Egypt on the
      Mediterranean Sea, receives different internal and external untreated pollutants
      affecting dramatically its water, sediments and biota. Surface and bottom water
      samples were collected bimonthly from this harbor for studying vertical, regional
      and monthly distributions of total suspended matter (TSM), total dissolved lead
      (TDPb) and total particulate lead (TPPb). The high surface TSM values coincided
      with air-borne dust, organic aggregates, plankton productivity and discharged
      wastes. The high TSM averages in winter resulted mainly from turbulence of the
      water column by wind action. The highest averages of TDPb in the petroleum and
      coal basins in the Western Harbor reflect their effects on the water column,
      while the lowest averages of TDPb and TPPb were found at a location far away from
      pollution sources. For the water column, the maximum and minimum monthly averages
      of TPPb and TDPb respectively in June reflect the increase in the rate of lead
      uptake by phytoplankton abundant in summer, favored by temperature elevation. The
      annual mean concentration of TPPb was nearly double that of TDPb, indicating that
      lead was transported to the Western Harbor mainly in particulate form. This
      reflects the high TSM content in the harbor water onto which a considerable part
      of lead was adsorbed.

PMID- 12787598
TI  - Antifouling herbicides in the coastal waters of western Japan.
AB  - Residue analyses of some antifouling herbicides (Diuron, Irgarol 1051 and the
      latter's degradation product M1, which is also known as GS26575), were conducted
      in waters collected along the coast of western Japan. In total, 142 water samples
      were collected from fishery harbours (99 sites), marinas (27 sites), and small
      ports (16 sites) around the Seto Inland Sea, the Kii Peninsula, and Lake Biwa, in
      August 1999. A urea-based herbicide, Diuron, was positively identified for the
      first time in Japanese aquatic environments. Diuron was detected in 121 samples
      (86%) up to a highest concentration of 3.05 microg/l, and was found in 86% of
      samples from fishery harbours, 89% from marinas, and 75% from ports. Four
      freshwater samples out of 11 collected at Lake Biwa contained Diuron. Neither
      Irgarol 1051 nor M1 was found in the lake waters, but both were found in many
      coastal waters. Irgarol 1051 was found in 84 samples (60%) at a highest
      concentration of 0.262 microg/l. The concentrations detected were of similar
      magnitude to those in our previous surveys, taken in 1997 and 1998. M1 was found
      in 40 samples (28%) up to a highest concentration of 0.080 microg/l. The
      concentrations detected were generally lower than those found in our previous
      surveys. The detection frequency among fishery harbours, marinas, and ports was
      57-70% for Irgarol 1051 and 25-30% for M1. Ninety-five per cent of the coastal
      waters in which M1 was detected also contained Irgarol 1051, and 93% of the
      samples in which Irgarol 1051 was detected also contained Diuron. These results
      clearly suggest that commercial ship-bottom paints containing both Diuron and
      Irgarol 1051 are used extensively in the survey area.

PMID- 12787599
TI  - Survey of dioxins in Tokyo Bay bottom sediment.
AB  - This paper examines dioxin profiles in bottom sediments from Tokyo Bay, Japan
      using sedimentation dating based on 210Pb measurements and dioxin measurements
      based on particle size distributions. Dioxin concentrations in surface sediment
      ranged from 3.2 to 52 pg-TEQ g(-1), with the concentrations in the bay back and
      central region being higher than those at the front of the bay. The vertical
      dioxin concentration in sediment core samples showed peak levels from years 1962
      to 1980, with the maximum being 110 pg-TEQ g(-1). Principal component analysis
      indicates that the main source of dioxins in bottom sediment from the back of bay
      are herbicides such as CNP, while in the front of bay atmospheric deposition due
      to incineration activities are responsible. Dioxins in bottom sediment were
      mainly found in the particles <75 microm in size.

PMID- 12787600
TI  - Crude oil bioremediation field experiment in the Sea of Japan.
AB  - Experimental bioremediation of crude oil was conducted for approximately 3 months
      in the intertidal zone of the Sea of Japan, Hyogo Prefecture. Artificial mixtures
      of weathered Arabian light crude oil and sand taken from the experimental site
      were wrapped in polyester net envelopes. The envelopes were placed in drum-shaped
      acrylic vessels with perforated sides to facilitate seawater exchange. The
      vessels were laid in the intertidal area. Slow release nitrogen and phosphorus
      synthetic fertilizer granules were added to the oil-sand mixtures in three
      different amounts. Some oil-sand mixtures were unfertilized controls. The oil
      sand mixtures were periodically sampled and changes in the composition of the
      residual oils were monitored. Oil samples were subjected to gas chromatography
      coupled with mass spectrometry for analysis of some representative semi-volatile
      aliphatic and aromatic compounds. All values for each analyte were normalized
      against that of hopane to evaluate the extent of oil biodegradation. Significant
      increases in the concentrations of both nitrogen and phosphorus were found in the
      fertilized sections in accordance with the amounts of added fertilizers. Although
      significant natural attenuation of oil was observed in the unfertilized sections,
      fertilization stimulated the degradation rate of the oil in the early stage of
      the experimental term. The extent of the oil biodegradation increased as the
      amount of added fertilizer increased. However, the final degradation efficiencies
      for each oil component in the fertilized sections were not significantly
      different from those in the unfertilized sections, and the degradation of each
      oil component had almost ceased after 6 weeks. We conclude that excessive amounts
      of macronutrients are required to accelerate oil biodegradation and that
      fertilization is only effective in the early stages.

PMID- 12787601
TI  - Study of the effect of water-soluble fractions of heavy-oil on coastal marine
      organisms using enclosed ecosystems, mesocosms.
AB  - Mesocosm facilities composed of 4 experimental and 2 reservoir tanks (1.5 m in
      diameter, 3.0 m in depth and 5 tons in capacity) made of FRP plastics, were
      constructed in the concrete fish rearing pond in the Fisheries Laboratory, The
      University of Tokyo. The water-soluble fraction of Rank A heavy residual oil was
      formed by mixing 500 g of the oil with 10 l of seawater, which was introduced to
      the 5000 l-capacity tanks. Experimental Run 4 was conducted from May 31 to June
      7, 2000. Oil concentrations in the tanks were 4.5 microg/l called LOW, and 13.5
      microg/l, called HIGH tank. Bacterial growth rates very quickly accelerated in
      the HIGH tank just after the loading of oil which corresponded with a high
      increase of bacterial cells in the same tank after 2 days. Later, bacterial
      numbers in HIGH tank rapidly decreased, corresponding with the rapid increase of
      heterotrophic nano-flagellates and virus numbers on the same day. Sediment traps
      were deployed at the bottom of the experimental tanks, and were periodically
      retrieved. These samples were observed both under light microscope and epi
      fluorescent microscope with UV-excitation. It was observed that the main
      components of the vertical flux were amorphous suspended matter, mostly
      originating from dead phytoplankton and living diatoms. It was further observed
      from the pictures that vertical transport of oil emulsions were probably
      conducted after adsorption to amorphous suspended matter and living diatoms, and
      were settling in the sediment traps at the bottom of the tanks. This means that
      the main force which drives the soluble fraction of oil into bottom sediment
      would be vertical flux of such amorphous suspended particles and phytoplankton.
      Further incubation of the samples revealed that the oil emulsions were degraded
      by the activity of autochtonous bacteria in the sediment in aerobic condition.

PMID- 12787602
TI  - Effects of spilled oil on microbial communities in a tidal flat.
AB  - Effects of spilled oil on microbial communities in tidal flats were examined by
      use of a simulator for a tidal flat ecosystem. The simulator is composed of a
      wave generator, a tide control device, and a tidal flat. Sediment for the tidal
      flat was obtained at a natural tidal flat in Hiroshima Bay, Japan. After
      stabilizing the benthic organisms, fuel oil C was added to the surface of the
      flat at 1 lm(-2). Although the total number of micro-organisms remained at 1.5
      3.5 x 10(9) cells g(-1) dry sediment irrespective of the addition of oil,
      bacterial communities which were analyzed based on the 16S rDNA showed clear
      changes after the addition of fuel oil C and after a subsequent recovery period.
      Bacterial colonies were randomly isolated from the oil-supplemented sediment
      during the experiments, and the isolates were examined for susceptibility to
      hydrocarbons in order to screen the oil-susceptible bacteria. The proportion of
      oil-susceptible bacteria in the isolates decreased with the addition of the oil.
      Oil-susceptible bacteria showed an inability to assimilate petroleum compounds as
      well as an inhibition of growth. The possibility of using oil-susceptible
      bacteria as an indicator of bioremediation in tidal flats was discussed.

PMID- 12787603
TI  - Impacts by heavy-oil spill from the Russian tanker Nakhodka on intertidal
      ecosystems: recovery of animal community.
AB  - The impact of a heavy-oil spill from the Nakhodka on an intertidal animal
      community, and the recovery process of animals from the damage were surveyed from
      the autumn of 1997 to the spring of 2001. The field study was carried out in the
      rocky coast of Imago-Ura Cove, located along the Sea of Japan, where clean-up
      operations for oil pollution had been conducted less intensely than in other
      polluted areas. We have examined individual number of each animal taxon by
      continuously placing a quadrat of 5 m width along the entire intertidal zone of
      the cove. A total of 76 invertebrate taxa including 57 species of mollusks, 10
      species of crustaceans were observed during the survey. The number of taxa
      increased from 1998 to 1999 in areas where the initial oil pollution was intense.
      Total individual number of benthic animals continued to increase from 1998 to
      2000 in the polluted areas. The impact of oil on benthic animals was different
      from species to species. Some species such as Cellana toreuma and Monodonta labio
      confusa increased rapidly after the oil spill, whereas other species such as
      Patelloida saccharina lanx and Septifer virgatus did not show any apparent
      temporal tendencies. Population size structure of P. saccharina lanx varied
      greatly among years, however that of M. labio confusa did not. For P. saccharina
      lanx, recruitment was unsuccessful in 1997, possibly due to the effect of oil
      pollution. These differences in responses to oil pollution among benthic animals
      are considered to be caused by the differences in habitat use, susceptibility to
      heavy-oil, life history and migration ability. The findings suggest that it took
      at least 2-3 years for the intertidal animal community to recover to its original
      level after the oil spill.

PMID- 12787604
TI  - Impacts of the Nakhodka heavy-oil spill on an intertidal ecosystem: an approach
      to impact evaluation using geographical information system.
AB  - A major heavy-oil spill from the Russian tanker Nakhodka occurred in the Sea of
      Japan on 2 January 1997. We investigated the impacts of this spill on a rocky
      intertidal ecosystem along the southern coast of the Sea of Japan. We selected
      Imago-Ura Cove as our study site to observe temporal changes along the oiled
      shore, because minimal cleaning effort was made in this area. Field surveys were
      conducted every autumn and spring from 1997 to 2000. We measured coverage by
      macroalgae in 1 x 1-m(2) quadrats and counted the animals in 5 x 5-m(2) quadrats
      along the intertidal zone. Changes in the ecosystem caused by the oil spill were
      analyzed by applying a geographical information system (GIS) to the Sea of Japan
      for the first time. The GIS showed that following the accident there were heavily
      oiled areas in sheltered regions, but these decreased over the three years. It
      also showed that coverage by macroalgae and the number of animals increased,
      although some species of algae with microscopic sporophyte generations, and some
      populations of perennial shellfish, remained stable or decreased during the study
      period. GIS was able to trace temporal changes in intertidal communities
      resulting from the impacts of heavy oil on flora and fauna at a spatial scale of
      10-100 m. GIS is thus a practical tool for visualizing, analyzing, and monitoring
      changes in an ecosystem polluted by oil, taking into account topographic
      differences along the coastline.

PMID- 12787605
TI  - Study on the fate of petroleum-derived polycyclic aromatic hydrocarbons (PAHs)
      and the effect of chemical dispersant using an enclosed ecosystem, mesocosm.
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) are one of the components found in oil
      and are of interest because some are toxic. We studied the environmental fate of
      PAHs and the effects of chemical dispersants using experimental 500 l mesocosm
      tanks that mimic natural ecosystems. The tanks were filled with seawater spiked
      with the water-soluble fraction of heavy residual oil. Water samples and settling
      particles in the tanks were collected periodically and 38 PAH compounds were
      analyzed by gas chromatography-mass spectrometry (GC-MS). Low molecular weight
      (LMW) PAHs with less than three benzene rings disappeared rapidly, mostly within
      2 days. On the other hand, high molecular weight (HMW) PAHs with more than four
      benzene rings remained in the water column for a longer time, up to 9 days. Also,
      significant portions (10-94%) of HMW PAHs settled to the bottom and were caught
      in the sediment trap. The addition of chemical dispersant accelerated dissolution
      and biodegradation of PAHs, especially HMW PAHs. The dispersant amplified the
      amounts of PAHs found in the water column. The amplification was the greater for
      the more hydrophobic PAHs, with an enrichment factor of up to six times. The
      increased PAHs resulting from dispersant use overwhelmed the normal degradation
      and, as a result, higher concentrations of PAHs were observed in water column
      throughout the experimental period. We conclude that the addition of the
      dispersant could increase the concentration of water column PAHs and thus
      increase the exposure and potential toxicity for organisms in the natural
      environment. By making more hydrocarbon material available to the water column,
      the application of dispersant reduced the settling of PAHs. For the tank with
      dispersant, only 6% of chrysene initially introduced was detected in the sediment
      trap whereas 70% was found in the trap in the tank without dispersant.

PMID- 12787606
TI  - Monitoring of DSP toxins in small-sized plankton fraction of seawater collected
      in Mutsu Bay, Japan, by ELISA method: relation with toxin contamination of
      scallop.
AB  - Monitorings were conducted on DSP toxins in mid-gut gland of scallop (mouse
      assay), cell numbers of toxic dinoflagellate species of Dinophysis, and
      diarrhetic shellfish poisoning (DSP) toxins in small-sized (0.7-5 microm)
      plankton fraction of seawater collected from surface (0 m) and 20 m depth at a
      station in Mutsu Bay, Aomori Prefecture, Japan, in 2000. A specific enzyme-linked
      immunosorbent assay (ELISA) was employed for the analysis of DSP toxins in small
      sized plankton fraction using a mouse monoclonal anti-okadaic acid antibody which
      recognizes okadaic acid, dinophysistoxin-1, and dinophysistoxin-3. DSP toxins
      were detected twice in the mid-gut gland of scallops at 1.1-2.3 MU (mouse units)
      g(-1) on 26 June and at 0.6-1.2 MU g(-1) on 3 July, respectively. Relatively high
      cell densities of D. fortii were observed on 26 June and 11 September, and may
      only contribute to the bivalve toxicity during late June to early July. D.
      acuminata did not appear to be responsible for the toxicity of scallops in Mutsu
      Bay in 2000. ELISA monitoring of small-sized plankton fraction in seawater could
      detect DSP toxins two weeks before the detection of the toxin in scallops, and
      could do so two weeks after the loss of the bivalve toxicity by mouse assay. On
      17 July, toxic D. fortii was detected at only small number, <10 cells l(-1), but
      DSP toxins were detected by the ELISA assay, suggesting a presence of other toxic
      small-sized plankton in seawater. For the purpose of reducing negative impacts of
      DSP occurrences, monitorings have been carried out hitherto on DSP toxins of
      bivalve tissues by mouse assay and on cell densities of "toxic" species of
      Dinophysis. Here we propose a usefulness of ELISA monitoring of plankton
      toxicity, especially in small-sized fraction, which are possible foods of
      mixotrophic Dinophysis, as a practical tool for detecting and predicting DSPs in
      coastal areas of fisheries grounds of bivalve aquaculture.

PMID- 12787607
TI  - Effects of deposit feeder Stichopus japonicus on algal bloom and organic matter
      contents of bottom sediments of the enclosed sea.
AB  - Algae growing in an enclosed sea may inhibit eutrophication because they absorb
      nutrients in the water. However, dead algae often cause anaerobic conditions in
      the water just above and on sediment after they are deposited on the bottom. We
      found that Stichopus japonicus inhibited the anaerobic processes coupling water
      sulfite production in sediment. The present study investigates whether S.
      japonicus inhibits algal flourish and influences sediment properties such as
      organic matter contents. Aquarium experiments were carried out at Komatsushima
      port in Tokushima Prefecture, western Japan. The aquaria used in the experiments
      were supplied with water directly from the adjacent sea (6 L/min), laid with sand
      of 10 cm depths, and lighted at 12 h intervals. Six aquaria each containing a sea
      cucumber from Komatsushima port and six aquaria without any were used in the
      experiments. Water temperature ranged between 9 and 15 degrees C during December
      2000 and April 2001. Salinity ranged between 32 per thousand and 34 per thousand.
      Algae began to cover the bottom of the aquaria without S. japonicus after 2
      weeks, whereas no growth was evident in the aquaria containing sea cucumbers.
      Chlorophyll a concentration in the surface sediment of the aquaria with S.
      japonicus (6.1+/-3.6 microg/g, mean S.D.+/-standard deviation) was significantly
      lower than that without it (60+/-17 microg/g, U-test, p<0.05). Phaeophytin
      concentration in the surface sediment of the aquaria with S. japonicus (0.9+/
      0.09 microg/g) was also significantly lower than that without it (4.5+/-1.0
      microg/g, U-test, p<0.05). TOC concentration in the surface sediment of the
      aquaria with S. japonicus (2.6+/-1.3 microg/g) was slightly lower than that
      without it (4.0+/-1.2 microg/g). These results showed that algal biomass and
      organic matter concentration of the bottom were decreased in the presence of S.
      japonicus. Therefore, S. japonicus inhibits algal bloom and decrease the contents
      of organic matter deposited on the bottom of enclosed sea areas.

PMID- 12787608
TI  - Recovery of fish stocks in the Seto Inland Sea.
AB  - The total amount of fisheries' yield in the Seto Inland Sea in 1999 was 571,000
      MT, consisting of 256,000 MT by fishing and 315,000 MT from aquaculture. About
      40,000 people engaged in the fishing and aquaculture industries, earned 129
      billion yen (1100 million US$) by fishing and 89 billion yen (770 million $US) by
      aquaculture. The averaged annual catch for the Seto Inland Sea by fishing was 13
      MT/km(2). Division into time periods in terms of eutrophication levels can be
      made: before 1960 when red sea bream were abundant with ecological divergence
      (before eutrophication), from 1960 to 1990 when the biomass of anchovy was large
      (during eutrophication), and after 1990 when the jellyfishes were abundant
      (excessive eutrophication or high N:P ratio). The fish production will decrease
      in the sea of jellyfishes. Actually, the amount of catch was 462,000 MT in 1982
      which decreased 265,000 MT in 1993, corresponding to 43% in twelve years, then
      keeping the same level. A big reduction was seen in the catches of the spotlined
      sardine, anchovy, Spanish mackerel, tiger puffer, short-necked clam, sea cucumber
      and others. The tiger puffer and Spanish mackerel were abundant as predators in
      the sea of anchovy. The biomass of anchovy was at its maximum in 1986 and
      decreased to less than one third in 1996. The stocks of tiger puffer and Spanish
      mackerel greatly decreased because of the higher fishing pressure compared to the
      anchovy stock. The fishing power of individual fisheries targeting on the tiger
      puffer and Spanish mackerel increased substantially when fishing vessel and
      fishing gear improved, resulting in an excessive fishing effort. A large quantity
      of small immature fishes is usually caught in the Seto Inland Sea, resulting in
      growth and/or recruitment overfishing for many species. Hence, it is necessary to
      promote management of the fisheries so as not to reduce the fish stocks, and to
      allow the Seto Inland Sea to return from being a sea of jellyfishes to a sea of
      anchovy, with decreased eutrophication levels.

PMID- 12787609
TI  - The nationwide investigation of endocrine disruptors in sediment of harbours.
AB  - Various types of endocrine disruptors or environmental hormones flow from their
      sources down into harbours through rivers and other watercourses, and are
      accumulated in sediment on the sea bottom. Tributyltin, which has been used as
      paint for ship bottoms, is considered one of the endocrine disruptors. In close
      cooperation with the other ministries and agencies, the Ports and Harbours Bureau
      of the Ministry of Land, Infrastructure and Transport carried out an
      investigation in 1999 to determine the actual condition of 12 endocrine
      disruptors in the sediment of 39 harbours, in order to gather fundamental data to
      be used in future examinations of policy. Furthermore, in 2000 the bureau chose
      seven harbours out of the above 39 harbours as subjects of an additional
      investigation regarding the surface distribution of endocrine disruptors in the
      harbour areas and the synchronistic change of accumulation of dioxin and other
      substances. As the result of the investigation regarding the surface distribution
      of endocrine disruptors accumulated in seven harbours, relatively high
      concentrations were measured in the innermost parts of harbours and the mouths of
      rivers. Synchronistic changes in the amount of dioxin and other substances
      accumulated in sediments of five harbours were determined. Small amounts of
      dioxin and other substances, including an especially small amount of coplanar
      PCBs, were found in the layers formed before or around 1950. Relatively large
      amounts of these substances were measured in the upper layers formed during
      roughly 1960-1990, though no significant yearly differences in concentration
      could be identified. This result coincides with the facts that, during roughly
      1960-1980, PCP and CNP were used as agricultural chemicals and full-scale
      production of PCBs started in 1960.

PMID- 12787610
TI  - Toxicity of 17alpha-ethynylestradiol and norethindrone, constituents of an oral
      contraceptive pill to the swimming and reproduction of cladoceran Daphnia magna,
      with special reference to their synergetic effect.
AB  - Toxicity of 17alpha-ethynylestradiol (EE2) and norethindrone (NOR), constituents
      of low dosage oral contraceptives, was assessed for the freshwater cladoceran
      Daphnia magna. Acute toxicity tests showed that 5 ppm of EE2, the highest
      concentration in this study, never inhibited swimming, whereas NOR inhibited
      swimming at >3 ppm: 48 h EC(50) for NOR was 6.41 ppm. Chronic toxicity tests were
      carried out for 25 days by measuring the number of offspring, moltings and sex
      ratios of neonates at 20, 100 and 500 ppb. EE2>100 ppb significantly decreased
      the number of offspring to 75% of the control; however, no effect was observed in
      molting and sex ratios at <500 ppb. NOR did not affect reproduction and sex
      ratios at <500 ppb. Mixture of EE2 (5.88 ppb) and NOR (94.12 ppb) also
      significantly decreased the number of offspring to 57% of the control. This
      result indicates the importance of examining synergetic effects of chemicals in
      the context of natural environments which face exposure to myriad chemicals.

PMID- 12787611
TI  - Livestock wastes as a source of estrogens and their effects on wildlife of Manko
      tidal flat, Okinawa.
AB  - The Manko tidal flat in the southern part of Okinawa Island is an important
      visiting and wintering area for migratory birds and was added to the Ramsar
      Convention Register of Wetlands in 1999. This area used to be an inlet extending
      to the inner part of Naha Port, but recent reclamation projects have restricted
      its connection to the East China Sea. As is typical in rural regions of
      subtropical islands, the inhabitants in the Manko basin raise livestock,
      especially pigs, without employing sufficient waste treatment methods. As sewage
      treatment works are considered to be one of the main sources of environmental
      estrogens in urban areas, the significance of livestock farming as a source of
      estrogens in rural area is examined in this study. In the present study, total
      estrogenic activities in water and sediment samples from the Manko tidal flat and
      its basin were measured using a recombinant yeast screen method. Estrogenic
      activities (equivalent to 17beta-estradiol, E2) were around 10 ng l(-1) in water
      samples and more than 10 microg kg(-1) in some sediment samples. In addition, the
      concentrations of estrone (E1) and E2 in water samples measured using LC/MS/MS
      indicated a high contribution of environmental estrogens from livestock wastes.

PMID- 12787612
TI  - Natural water-purification system observed in a shallow coastal lagoon: Matsukawa
      ura, Japan.
AB  - Field surveys and in situ experiments were conducted in the shallow Matsukawa-ura
      in summer to evaluate the biological efficiencies of shallow-water areas for
      preserving coastal ecosystems. In Matsukawa-ura (5.8 km(2)), the suspension
      feeding bivalves Ruditapes philippinarum and Crassostrea gigas were the dominant
      animals--their total biomasses (wet weight) were estimated to be 3.4 x 10(6) and
      2.3 x 10(6) kg, respectively. Ulva sp. and Zostera marina were the dominant
      macrophyte species during the summer, with standing crops estimated to be 0.29 x
      10(6) and 0.20 x 10(6) kg, respectively. The dissolved inorganic nitrogen (DIN)
      uptake rates for Ulva sp. and Z. marina were determined by in situ experiments.
      An ecological model calculated on the basis of the observed dataset showed that,
      in comparison with tidal exchange, a significant amount of particulate organic
      matter was removed by bivalve filtration and a considerable quantity of DIN was
      removed by macrophyte species.

PMID- 12787613
TI  - The French approach to managing water resources in the Mediterranean and the new
      European Water Framework Directive.
AB  - The main content of the new European Water Framework Directive is presented.
      Within its river basin management approach, a special mention of coastal waters
      status is made. Among the issues at stake are the setting up of river basin
      management plans, including coastal waters, and water quality assessment system
      leading to an harmonized definition of quality objectives and their appropriate
      indicators. The Rhone-Mediterranean-Corsica Water Master Plan, launched in 1996,
      is considered to be well fitted to this river basin approach and the necessary
      tools which go with it. It shows up how a river quality assessment system (SEQ)
      can be adapted to the coastal waters and how it can progressively lead to an
      efficient set of publishable environmental and performance indicators. Since
      planning and implementation are devolved to the lowest appropriate level, a close
      look is then been given at how such a system can work at the local level through
      different selected case studies on the French Mediterranean coast. In conclusion,
      some guidelines are drawn up for future initiatives towards integrated coastal
      area and river basin management.

PMID- 12787614
TI  - Finnish strategies for reduction and control of effluents to the marine
      environment--examples from agriculture, municipalities and industry.
AB  - The most serious environmental problem encountered in the Baltic Sea is
      eutrophication. Finland finalised in spring 2002 its national Programme for the
      Protection of the Baltic Sea. The programme contains more than 30 measures for
      improving the state of the Baltic Sea and protecting the marine environment.
      Total national investments during the next 10-15 years will amount to EUR 300-370
      million. The highest annual cost will be environmental support to agriculture.
      The bulk of the rest of the money will be used for nitrogen purification of
      municipal wastewater, improvement of water protection in dispersed settlement
      areas, and investments to improve maritime safety and decrease the risks of oil
      spills.

PMID- 12787615
TI  - Effluent trading for water quality management: concept and application to the
      Chesapeake Bay watershed.
AB  - This paper examines the present and potential role of effluent trading in water
      quality management. In particular, it focuses upon the case of the Chesapeake Bay
      on the east coast of the US, where the implementation of a trading system has
      been discussed and undertaken. Potential benefits of effluent trading include
      advantages such as the following: (1) With appropriate monitoring and
      enforcement, the total pollutant loadings can be kept at or below the
      prespecified level. (2) New and expanding dischargers can be accommodated, as
      long as they purchase credits. (3) Abatement costs of pollutants can be reduced.
      (4) Flexible regulations incorporating trading can reduce the incentive for
      industries to relocate to areas with less stringent water quality regulation. (5)
      Broader environmental goals can be addressed, such as wildlife habitat provision
      and endangered species protection. (6) Preliminary studies with a view to trading
      system implementation encourage discussion and dialogue among stakeholders, and
      positively foster concerted, holistic solutions for maintenance of water bodies.

PMID- 12787616
TI  - International survey on the distribution of stranded and buried litter on beaches
      along the Sea of Japan.
AB  - The distribution and abundance of marine litter on 26 beaches along the Sea of
      Japan were investigated from September to November 2000. The mean concentration
      of stranded litter in Japan and Russia was 2144 and 1344 g/100 m(2),
      respectively. The mean number of pieces of stranded litter in Japan and Russia
      was 341 and 20.7/100 m(2), respectively. The most abundant type of stranded
      litter was plastic, which accounted for 40-80 % of the total items in terms of
      weight and number. The mean concentration of buried litter in Japan and Russia
      was 9.03 and 2.70 g/m(2), respectively. The total weight ratio of buried litter
      to stranded litter in the samples was 0.65, suggesting the significance of buried
      litter when evaluating the status of litter on beaches. Resin pellets were found
      on 12 Japanese beaches, but on none of the Russian beaches.

PMID- 12787618
TI  - Landscape mapping of the Russian Black Sea coast.
AB  - The purpose of this investigation is to study structure, evolution and present
      ecological state of background and anthropogenically modified landscapes of the
      Abrau Peninsula. This region has been recommended as one of the main conservation
      sites on the Russian Black Sea coast due to its relatively low anthropogenic
      transformation and its historical importance. The ecological situation is
      aggravated today by the construction of a pipe-line and oil terminal near
      Novorossiysk and by an increase in unregulated recreation activity within the
      peninsula's narrow coastal zone. A special landscape-ecological map has been
      compiled for the model area. All ecosystems shown on the map can be grouped into
      four main categories based on changes of landscape structure resulting from
      direct impact of human activity and indirect impact mainly from chemical
      pollution. Ecosystems exhibiting a high degree of transformation are more typical
      for regions characterized by settlements, vineyards and the coastal recreation
      zone. Ecosystems with moderate changes also exist in the coastal area, including,
      for example, some unique ecosystems with pine-tree forests, pistachio-juniper and
      juniper open-lands. Nearly 50% of pine-tree (Pinus pithyusa) forests are in the
      fourth and fifth stages of recreation degradation. Some protection measures are
      suggested to maintain biodiversity and sustainable development of these coastal
      landscapes and to improve their current condition.

PMID- 12787617
TI  - The status of the ecological environment and a proposed protection strategy in
      Sanya Bay, Hainan Island, China.
AB  - Sanya Bay encompasses a high diversity of natural habitats, ranging from coral
      reefs, rocky and sandy shores and mudflats to mangroves. Seasonal physicochemical
      and biological investigations were conducted from 1998 to 1999 and again in April
      2000. Water-related environmental quality in Sanya Bay is in good condition. The
      levels of dissolved oxygen, nitrogen, phosphorus and heavy metals are within the
      first class of National Seawater Quality Standards for China. Annual mean values
      of chlorophyll a of 0.93 mg m(-3) and phytoplankton primary productivity of 440.8
      mgC m(-2)d(-1), respectively, were found in the waters, both of which show a
      significant correlation with inorganic nitrogen. A mean new productivity of 144.6
      mgC m(-2) d(-1) was recorded in summer. Sanya Bay is rich in natural resources
      and biodiversity with 235 species of phytoplankton and 129 species of zooplankton
      identified in the survey. The annual mean abundance of phytoplankton and
      zooplankton were 1564 x 10 cells m(-3) and 121 individuals m(-3), respectively,
      with an annual mean zooplankton biomass of 129 mg m(-3). A total of 243 species
      of fish were sampled in the survey including many of high economic value. Three
      hundred and eighty-four species of benthos in 121 families were found by mud
      sampling and trawling. The average biomass of benthic organisms was 11.55 gm(-2),
      with a density of 31 individuals m(-2). Molluscs were the dominant group,
      followed by crustaceans; coelenterates exhibited the lowest biomass. One hundred
      and twenty-six species from 48 families of intertidal organisms were collected by
      frame sampling, with a mean annual biomass of 644.7 gm(-2) and average density of
      816 individuals m(-2). The highest biomass of 1673.5 gm(-2) was collected in a
      coral reef region, while the highest density of 1219 individuals m(-2) occurred
      in a mangrove region. The coastline is characterized by coral reefs that accounts
      for 30% of the total coastline length in the bay, so coral reefs are a key
      ecosystem that are important for maintaining the regional marine resources and
      biodiversity. We need to pay much more attention to such diverse marine resources
      to maintain the integrity and function of these coastal ecosystems.

PMID- 12787619
TI  - Approaches to environmental restoration of a polluted harbour with submerged
      archaeology: the Alexandria case study.
AB  - Many invaluable underwater buildings of archaeological interest in Alexandria
      were discovered in 1996 at different sites in the Eastern Harbour of Alexandria.
      There is a belief that the best way to protect these invaluable heritages is to
      transfer them to an underwater park or museum. Obviously, the execution of such a
      project depends essentially upon the water quality (including water transparency)
      improving in the future. The harbour is presently polluted by discharge of
      wastewater effluents from different sources. It has recently been decided to
      restore this important coastal area through: (1) stopping the direct discharge of
      wastewater effluents into this semi-enclosed harbour in 1993 and (2) gradually
      reducing the discharge of the municipal wastewater through marine outfalls at two
      sites lying at the outer sides of the harbour. Zero discharge is expected to be
      effective by the end of the year 2001. The present work, therefore, is a follow
      up of the study of water quality in the harbour after 1993: in 1996 and 1999
      2000. The water quality of an open sea reference station was also studied for
      comparison. The results reveal occurrence of an improvement of the environmental
      conditions in the harbour. The water has turned from being eutrophic to
      mesotrophic. The harbour is expected to become meso/oligotrophic as soon as the
      complete cessation of the discharge from the two outside sources is attained.

PMID- 12787620
TI  - Ecology and restoration techniques for Sargassum beds in the Seto Inland Sea,
      Japan.
AB  - Due to the reduction and degradation of coastal areas in Japan by land
      reclamation and anthropogenic perturbations, from the point of view of
      conservation of the coastal environment, the restoration of Sargassum beds is
      essential. Between 1978 and 1991, 6400 ha of seagrass and seaweed beds have been
      lost along the Japanese coast, of which Sargassum beds were 22%. New techniques
      for Sargassum bed restoration are summarized based on three coastal engineering
      techniques. (1) Construction of shallow and gentle sloping bottom substrata have
      been shown to be effective for the reestablishment of 'management-free seagrass
      and Sargassum beds' on developed coasts. (2) Seeding or transplanting using
      artificial substratum for extension of nursery and fishing grounds around natural
      Sargassum beds. (3) Periodic transplanting of Sargassum plants using artificially
      produced seedlings is effective to produce niches to allow faunal re-colonization
      in severely polluted and sparsely vegetated area. However, prior to
      implementation, the suitability and limitations of these three techniques
      requires to be ascertained for effective Sargassum bed restoration.

PMID- 12787621
TI  - Environmental management of marine fish culture in Hong Kong.
AB  - Marine fish farming is an important commercial practice in Hong Kong. Marine fish
      farms located in eutrophic coastal waters often face the threat of severe
      dissolved oxygen depletion associated with algal blooms and red tides. On the
      other hand, mariculture activities also contribute to pollution. The sustainable
      management of mariculture requires proper siting of the fish farms and stocking
      density control. Both of these are related to the carrying capacity of the water
      body concerned, which is mainly governed by its flushing characteristics. A
      simple method to determine the carrying capacity of a fish farm has been
      developed by using three-dimensional (3D) hydrodynamic modelling and its
      effective coupling with a diagenetic water quality model. A systematic
      methodology using numerical tracer experiments has been developed to compute the
      tidal flushing in a fish farm. The flushing time is determined from the results
      of a numerical tracer experiment using robust 3D hydrodynamic and mass transport
      models. A unit tracer concentration is initially prescribed inside the region of
      interest and zero elsewhere; the subsequent mass transport and the mass removal
      process are then tracked. The fish farms are usually situated in well-sheltered
      shallow embayments and may not connect directly to the open water. It is found
      that it is necessary to define both "local" and "system-wide" flushing times to
      represent the effectiveness of the mass exchange with the surrounding water body
      and the open sea respectively. A diagenetic water quality model simulating the
      sediment-water-pollutant interaction is employed to address the response of the
      water column and the benthic layer to pollution discharges. With the flushing
      rate reliably computed, the carrying capacity of the fish farm can be determined
      in terms of key water quality parameters: chlorophyll-a, dissolved oxygen,
      organic nitrogen and potential lowest dissolved oxygen level on a day of
      negligible photosynthetic production. The predictions are well-supported by field
      data.

PMID- 12787622
TI  - Set-up of a decision support system to support sustainable development of the
      Laguna de Bay, Philippines.
AB  - Over recent decades, population expansion, deforestation, land conversion,
      urbanisation, intense fisheries and industrialisation have produced massive
      changes in the Laguna de Bay catchment, Philippines. The resulting problems
      include rapid siltation of the lake, eutrophication, inputs of toxics, flooding
      problems and loss of biodiversity. Rational and systematic resolution of
      conflicting water use and water allocation interests is now urgently needed in
      order to ensure sustainable use of the water resources. With respect to the
      competing and conflicting pressures on the water resources, the Laguna Lake
      Development Authority (LLDA) needs to achieve comprehensive management and
      development of the area. In view of these problems and needs, the Government of
      the Netherlands was funding a two-year project entitled 'Sustainable Development
      of the Laguna de Bay Environment'.A comprehensive tool has been developed to
      support decision-making at catchment level. This consists of an ArcView GIS
      database linked to a state-of-the-art modelling suite, including hydrological and
      waste load models for the catchment area and a three-dimensional hydrodynamic and
      water quality model (Delft3D) linked to a habitat evaluation module for the lake.
      In addition, MS Office based tools to support a stakeholder analysis and
      financial and economic assessments have been developed. The project also focused
      on technical studies relating to dredging, drinking water supply and
      infrastructure works. These aimed to produce technically and economically
      feasible solutions to water quantity and quality problems. The paper also
      presents the findings of a study on the development of polder islands in the
      Laguna de Bay, addressing the water quantity and quality problems and focusing on
      the application of the decision support system.

PMID- 12787623
TI  - Achieving a paradigm shift in environmental and living resources management in
      the Gulf of Guinea: the large marine ecosystem approach.
AB  - The Gulf of Guinea is situated in the narrow protrusion of eastern Equatorial
      Atlantic between latitudes 2 degrees S and 5 degrees N and longitudes 8 degrees W
      to 12 degrees E, spanning a coastline length of approximately 130 nautical miles.
      The dominant feature of this shallow ocean off the coast of countries in Western
      Africa is the Guinea Current. The distinctive bathymetry, hydrography,
      productivity and trophodynamics of this shallow ocean qualify it as a large
      marine ecosystem (LME) and is indeed recognized as the number 28 of the 64
      delineated LMEs globally. This area is one of the world's productive marine areas
      that is rich in fishery resources, oil and gas reserves, precious minerals and an
      important global reservoir of marine biological diversity. Unfortunately,
      pollution from residential and industrial sources has affected the waters of the
      Gulf of Guinea resulting in habitat degradation, loss of biological diversity and
      productivity, and degenerating human health. In reversing this trend of marine
      environmental degradation, the countries of the region adopted an integrated and
      holistic approach using the LME concept to sustainably manage the environmental
      and living resources of the region. The concept is predicated on the fact that
      marine environmental pollution and living resources respect no political or
      geographical boundaries and so require a holistic and regional approach for its
      management. The Gulf of Guinea countries through the Global Environment facility
      funded regional/communal project on water pollution control and biodiversity
      conservation achieved a paradigm shift in living resources and environmental
      management in the region using the LME concept.

PMID- 12787624
TI  - Economic and geographic backgrounds of land reclamation in Japanese ports.
AB  - Under the present legal system, environmental impacts are usually assessed on
      condition that reclamation plans are given clearly. Although impact magnitude
      depends on reclamation scales, the economic and geographic backgrounds of
      reclamation scales have been rarely analyzed. Hence, properties of reclamation in
      port districts were investigated. The long-term trend showed that the area newly
      reclaimed per year has decreased rapidly since the first oil crisis; while the
      speed of the decrease dropped after 1984. The distributions of increased
      reclamation area planned against its water depth had one or two peaks in 1989
      1991 and 1996-1998. These peaks resulted mainly from "island-type" reclamation,
      and shifted from shallow to deep sites. The areas of port districts had major
      effects on increased area of reclamation and maximum water depth in 1989-1991,
      while such effects were not observed in 1996-1998. Land price had some effects
      for deepening water depth of reclamation in both periods.

PMID- 12787625
TI  - Economic valuation of the Seto Inland Sea by using an Internet CV survey.
AB  - We estimate the economic value of the natural environment damaged in the Seto
      Inland Sea after the introduction of the Law on Temporary Measures for the
      Environmental Conservation of the Seto Inland Sea (Setouchi Law) and the value of
      the natural environment that survived, using a Contingent Valuation (CV) survey
      on an Internet web site. The CV survey contains three plans. Plan 1 is to restore
      4 ha of reclaimed land. By estimating the Willingness To Pay (WTP) for plan 1, we
      can appraise the value of the natural environment that was damaged as a result of
      the original reclamation. Plan 2 is to transplant Zostera (eel-grass) into an
      area of 10 ha offshore. Plan 3 is to preserve the shore area, a natural habitat
      for rare animal species, under the National Trust Program. From the WTP for plans
      2 and 3, we can estimate the value of the shore area and the areas a little
      farther offshore. The value of the natural environment damaged in the Seto Inland
      Sea as a result of reclaiming projects after the introduction of the Setouchi Law
      and the value of the existing natural environment of the Seto Inland Sea from the
      WTP for the plans were estimated to about 172 trillion yen (1.46 trillion
      dollars) and about 424 trillion yen (3.60 trillion dollars), respectively. The
      results indicate that in the 25 years since the introduction of the Setouchi Law,
      we have degraded every year about 6.88 trillion yen (58.5 billion dollars) worth
      of the natural environment by reclaiming. Some seaweed farms and natural shore
      areas, natural habitats to rare marine life-forms like the horseshoe crab and the
      fiddler crab have survived, but their value amounts to about 80% of Japan's GDP.

PMID- 12787626
TI  - The roles and limitations of newspapers in environmental reporting. Case study:
      Isahaya Bay land reclamation project issue.
AB  - This paper looks at Japanese newspaper coverage of environmental issues, focusing
      on the case of the controversy over the Isahaya Bay land reclamation project.
      This project was first planned in the early 1950s and construction began in 1989.
      Local activists groups began raising questions about the project in the 1970s,
      focusing on the environmental degradation that would result, but they did not
      succeed in having their opinions discussed widely in the media until it was too
      late to prevent completion. Only after the dramatic images of the last slab of
      the seawall falling into place, was there intense media coverage of the project.
      The attention paid to the project by the media did much to inform the public
      about the effects of large-scale public works projects on the environment. Yet an
      analysis of the newspaper coverage shows that the media played mostly a
      "spectator" role in the controversy, merely reacting to events. A more active,
      "watch-dog" role would be necessary for the media to uncover threats to the
      environment in time for the public to be educated about such issues and have a
      chance to influence crucial official decisions.

PMID- 12787627
TI  - Education challenges in the North Sea area.
AB  - This paper introduces the North Sea as a fast evolving coastal ecosystem. The
      variability of natural conditions relates to the global climatic change and to
      human disturbances, which originate regionally. Education is an integral part of
      the strategy to improve environmental awareness. Considering contemporary
      challenges for educating the wider public about the main issues of environmental
      concern, attention is paid to various plans, which are being developed in North
      Western Europe from primary schools to universities. "Learning for life" relies
      on an opening of the vocation of traditional universities and on the creation of
      a European university. Sharing resources in a competitive environment is one
      response given by British universities in the framework of a Discipline Network
      in Coastal Sciences and Management in 1996-2000. Networking is truly the key to a
      fast evolving teaching and learning context, notably in relation to ever
      developing information and communication technologies. The dissemination of
      scientific information is primordial in this context; a case study relating to
      the European project "Marine biodiversity in Europe" (BIOMARE) demonstrates the
      need for an elaborated strategy leading to socio-economic considerations.
      Empowering communities and governance are the main possible outcomes of such an
      enlarged approach to education, involving teachers, students, researchers,
      professionals, and volunteers. Proposals are made for amplifying the involvement
      of non-scientists into scientific research and its applications to management.
      Finally, a case is made for facilitating the mobility of all concerned, with a
      view to annihilate language and cultural barriers.

PMID- 12787628
TI  - Coastal seas as a context for science teaching: a lesson from Chesapeake Bay.
AB  - Lessons that employ authentic environmental data can enhance the ability of
      students to understand fundamental science concepts. This differs from
      traditional "environmental education" in that school curricula need not set aside
      time for educators to teach only environmental topics. Rather, the "environment"
      is used to advance student learning in science and technology. The success of
      this approach depends on programs that encourage scientists to communicate more
      effectively with teachers at all education levels. The expanding diversity of
      research and monitoring activities on the world's marine waters constitutes an
      outstanding potential education resource. Many of these projects involve remote
      sensing with sophisticated instrumentation and employ Internet technology to
      compile measurements, interpret data using graphs and satellite imagery, and
      share the results among scientific colleagues and the general public alike.
      Unfortunately, these resources, which constitute a much shortened path between
      research findings and textbook presentation, are seldom interpreted for use by K
      12 educators. We have developed an example that uses the Chesapeake Bay as a
      paradigm to demonstrate how such interpretation can assist educators in teaching
      important principles in physical oceanography and marine ecology. We present this
      example using PowerPoint to conduct a virtual tour of selected Internet sources.
      Our example begins with the conceptual "salt wedge" circulation model of
      Chesapeake Bay as a partially mixed estuary. Teachers have the opportunity to
      explore this model using salinity, temperature, and dissolved oxygen data taken
      from a research vessel platform during summer professional development programs.
      This source of authentic data, originally obtained by teachers themselves,
      clearly demonstrates the presence of a picnocline and deep-water anoxia. Our
      lesson plan proceeds to interpret these data using additional Internet-based
      resources at increasing scales of time and space. The "salt wedge," picnocline,
      and anoxia are examined using graphics derived from data taken by researchers
      using "ScanFish," a towed instrument that samples temperature, salinity, and
      dissolved oxygen at a resolution of only a few meters vertically and
      horizontally. The seasonal dynamics of these parameters at a given location are
      interpreted using biweekly monitoring data obtained as part of the state-federal
      Chesapeake Bay Program. The influence of annual variations in freshwater input is
      examined using stream flow data from US. Geological Survey gauging stations.
      Satellite remote sensing images from the TOPEX/Poseidon project are used to show
      how El Nino and La Nina events in the mid-Pacific affect the Chesapeake Bay
      system via rainfall on its watershed. Finally, the life cycle of the blue crab
      (Callinectes sapidus) is presented to show how an estuarine organism has adapted
      to this truly unique and dynamic coastal environment.

PMID- 12787629
TI  - Conservation of biodiversity of the coastal resources of Sundarbans, Northeast
      India: an integrated approach through environmental education.
AB  - The Indian Sundarbans, a diversified coastal wetland on the southern fringe of
      the State of West Bengal, harbors a luxuriant biodiversity and acts as a
      potential refuge of living marine resources. Girdled with thick mangrove foliage,
      this estuarine delta system offers an excellent nursery ground for most of the
      brackishwater finfish and shellfish. Since supply of hatchery-produced tiger
      prawn seed (Penaeus monodon) is highly inadequate in West Bengal, the aquaculture
      farms of this region largely depend on the supply from natural resources. Being
      motivated by a regular cash income, the majority of coastal people from
      Sundarbans have adopted prawn seed collection as their profession almost
      throughout the year as an important source of earning. The users are neither
      trained nor guided at any stage from collection to marketing and are fully
      dependent on traditional methods. They first sort out the tiger prawn seeds
      (mainly the postlarval stage PL 20) accounting only 0.25-0.27% of the total catch
      and thereafter the major portion of the haul are thrown away on the beach flats
      or the tidal mudflats. This wasted by-catch contains the juveniles of economic
      and uneconomic varieties of finfish and shellfish along with a bulk of
      holoplankters and meroplankters (non-target species). This practice causes
      several ecological and occupational consequences, namely, (i) the huge
      destruction of the pelagic biota that can lead to severe stock depletion as well
      as hamper the energy transference through the marine ecosystem food webs; (ii)
      constant dragging of nets along the coast and tidal creeks paves the way for soil
      erosion, uprooting the mangrove seedlings and saltmarsh vegetation; (iii) the
      water quality is deteriorating in the catchment areas due to mud erosion and (iv)
      due to constant contact with the seawater, the collectors are affected with
      waterborne diseases, skin infections, reproductive tract disease in women and
      many other contagious diseases. This paper, in addition to identifying the
      challenge to environmental quality and resource abundance, emphasizes the need
      for grass-root public education so that local people come to understand, support
      and implement sustainable resource conservation and environmental protection
      activities now and in the future. As a follow-up course of action, the authors
      have initiated a general awareness program for developing consciousness among the
      coastal people regarding proper use of natural resources. Initiatives are taken
      for educating coastal people by holding workshops and seminars with the use of
      educational resource materials. Exclusive awareness camps and grass root level
      training for coastal people are also being proposed as a future course of action
      by means of exhibitions, audiovisuals etc. It is proposed that local government
      bodies come forward to mitigate this problem with scientific and rational
      approaches and to take proper actions towards conservation.

PMID- 12787630
TI  - Marine and coastal environmental awareness building within the context of
      UNESCO's activities in Asia and the Pacific.
AB  - UNESCO is one of the specialized agencies under the United Nations charged with
      the advancement and improvement of education, social and natural sciences,
      culture and communication. This global mandate translates into programmes in the
      field tailored to the member states' specific requirements that build on the full
      breadth of expertise available in UNESCO. Environmental awareness building is an
      integral component of many of UNESCO's programmes. This paper describes how
      UNESCO addresses the need for awareness building in a variety of settings under
      different programmes and sectors. A first example is taken from the work of the
      education sector, which aims at introducing innovative learning methods and
      curricula that change or cultivate the perspective of people of all ages on
      sustainable development. The second example is taken from the Man and Biosphere
      Programme. The Biosphere Reserve concept has had a long history within UNESCO and
      is increasingly applied to protected areas in the coastal zone. Notable examples
      are Ranong Biosphere Reserve in Thailand, Can Gio Biosphere Reserve in Vietnam
      and the Island of Palawan in the Philippines. The concept is currently
      experiencing a revival as more and more countries realize the importance of
      striking a balance between human development and strict conservation. Many people
      know about UNESCO through the so-called World Heritage Sites. These are sites
      that are recognized by the world community as particular monuments, either
      natural or cultural, that warrant preservation for the whole of mankind. In the
      Asia-Pacific region, there are quite a number of coastal and marine sites that
      have been designated as natural world heritage sites, e.g. Halong Bay in Vietnam,
      the Komodo marine national park, Indonesia, the Great Barrier Reef in Australia,
      East-Rennell Island in the Solomon Islands, and Tubbataha Reef in the
      Philippines. The need for a cross-sectoral approach is evident under the so
      called Coastal Zone and Small Islands endeavour, which aims at assisting Member
      States towards environmentally sound, socially equitable and culturally
      appropriate development in coastal regions and in small islands. Four examples of
      current pilot projects (Surin Island, Thailand, Jakarta Bay, Indonesia, Upolo
      Island, Samoa and Ulugan Bay, the Philippines) are highlighted. Each setting and
      each audience requires a different strategy. UNESCO's strength is to learn from
      all these experiences and make such new insights universally available and to put
      novel concepts into practice.

PMID- 12787631
TI  - Coagulation factor VIII: structure and stability.
AB  - Factor VIII (FVIII), a coagulation factor in the blood, is one of the most
      complex proteins known today. To facilitate the rapid development of a more
      convenient and safer FVIII product and to improve the quality of life for
      hemophilia patients, this short article reviews the recent investigations on the
      structure, activity, and more importantly, stability of FVIII.

PMID- 12787632
TI  - Evaluation of different calorimetric methods to determine the glass transition
      temperature and molecular mobility below T(g) for amorphous drugs.
AB  - The purpose of the present study was to compare different calorimetric methods
      used to determine the glass transition temperature (T(g)) and to evaluate the
      relaxation behaviour and hence the stability of amorphous drugs below their T(g).
      Data showed that the values of the activation energy for the transition of a
      glass to its super-cooled liquid state qualitatively correlate with the values of
      the mean molecular relaxation time constant of ketoconazole, itraconazole and
      miconazole, three structurally related drugs. Estimation of the molecular
      mobility by activation energy calculation indicated that loperamide was more
      stable than its two building blocks T263 and R731. It was further shown that the
      most commonly used approach to determine T(g) (T(g (1/2 c(p))) leads to erroneous
      values when enthalpy recovery is significant. In this case, an alternative method
      based on enthalpic considerations leads to results in accordance to basic
      thermodynamics. Estimation of molecular mobility based on activation energy
      calculations is therefore considered to be a valuable alternative for the method
      based on measurement of the extent of relaxation. When enthalpy relaxation is
      important, the use of T(g 1/2c(p)) leads to an overestimation of the T(g).

PMID- 12787633
TI  - Characterization of monoclinic crystals in tablets by pattern-fitting procedure
      using X-ray powder diffraction data.
AB  - The purpose of this study is to characterize the monoclinic crystals in tablets
      by using X-ray powder diffraction data and to evaluate the deformation feature of
      crystals during compression. The monoclinic crystals of acetaminophen and benzoic
      acid were used as the samples. The observed X-ray diffraction intensities were
      fitted to the analytic expression, and the fitting parameters, such as the
      lattice parameters, the peak-width parameters, the preferred orientation
      parameter and peak asymmetric parameter were optimized by a non-linear least
      squares procedure. The Gauss and March distribution functions were used to
      correct the preferred orientation of crystallites in the tablet. The March
      function performed better in correcting the modification of diffraction intensity
      by preferred orientation of crystallites, suggesting that the crystallites in the
      tablets had fiber texture with axial orientation. Although a broadening of
      diffraction peaks was observed in acetaminophen tablets with an increase of
      compression pressure, little broadening was observed in the benzoic tablets.
      These results suggest that "acetaminophen is a material consolidating by
      fragmentation of crystalline particles and benzoic acid is a material
      consolidating by plastic deformation then occurred rearrangement of molecules
      during compression". A pattern-fitting procedure is the superior method for
      characterizing the crystalline drugs of monoclinic crystals in the tablets, as
      well as orthorhombic isoniazid and mannitol crystals reported in the previous
      paper.

PMID- 12787634
TI  - Convolution method to predict drug concentration profiles of 2,3,5,6
      tetramethylpyrazine following transdermal application.
AB  - The objective of this work is to predict the systemic drug concentration of
      2,3,5,6-tetramethylpyrazine (TMP) following transdermal application in rabbits
      from the in vitro skin permeation data. The in vitro skin permeation was studied
      in Franz diffusion cells. Pharmacokinetic evaluation of TMP following transdermal
      application and bolus intravenous administration were carried out in New Zealand
      White (NZW) rabbits. Drug concentration-time curve following transdermal
      application was predicted via the convolution procedure using an in vitro skin
      permeation data as a weighting function, and the intravenous data as an unit
      impulse response. The results showed that the predicted drug concentration
      following transdermal application by convolution method was in good agreement
      with the observed drug absorption profiles. These findings indicated that in
      vitro skin permeation tests could be useful to predict in vivo drug absorption
      profiles following transdermal application.

PMID- 12787635
TI  - Targeted retentive device for oro-dental infections: formulation and development.
AB  - Fibers loaded with amoxycillin trihydrate were prepared for oro-dental infections
      using melt spinning technique. Ethylene vinyl acetate, a biocompatible polymer
      was used for providing controlled release effect over a period of several days.
      The fibers were evaluated for in vitro release in alkaline borate buffer pH 8.1
      in a biological shaker which was rotated at 50 rpm at 37 degrees C. In situ
      studies were carried out in continuous flow through apparatus which simulated the
      conditions of periodontal pocket. Microbiological evaluation was carried out on
      strains commonly implicated in oro-dental infections namely S. aureus, S. mutans,
      and Bacteroides cereus. Results of in vitro release studies revealed that the
      effect was sustained over a period of 6 days and followed Fickian diffusion
      mechanism. In situ release study samples were well above the minimum inhibitory
      concentration of the drug. These samples were effective in inhibiting the growth
      of the above-mentioned strains. The optimized formulation was characterized for
      general appearance, content uniformity, and SEM. Stability studies carried out on
      the formulation showed the degradation rate constant value of 2.79 x 10(-4) per
      day. Retentive fibers were found to be very effective in controlled delivery of
      amoxycillin, and hence can be feasible alternative to systemic administration.

PMID- 12787636
TI  - Development and optimisation of alginate-PMCG-alginate microcapsules for cell
      immobilisation.
AB  - Mechanical stability, uniformity of size, complete encapsulation of cells and
      optimal microenvironment are major challenges in the design and development of
      microcapsules for cell immobilisation purposes. In this work, a novel
      microcapsule chemistry based on polyelectrolyte complexation between alginate and
      poly(methylene-co-guanidine) (PMCG) is presented. We have characterised the
      effect of PMCG concentration and time of exposure on microcapsule diameter and
      membrane thickness, selecting a PMCG concentration of 0.5% (v/v) and an exposure
      time of 1 min as optimal parameters for a correct coating. Afterwards, the
      mechanically most resistant alginate-PMCG-alginate (A-PMCG-A) microcapsule type
      was chosen according to two different stability studies. Beads with a solid core
      and an inhomogeneous internal configuration resulted in stronger microcapsules.
      Further, the selected A-PMCG-A beads presented both an increased stability
      compared to classical Ca(2+)/alginate and alginate-poly-L-lysine-alginate (APA)
      microcapsules, and had an adequate microenvironment for cell viability. This new
      chemistry allows the controlled adjustment of microcapsule size and wall
      thickness, offering new alternatives for cell transplantation.

PMID- 12787637
TI  - Comparison of the compression characteristics between new one-step dry-coated
      tablets (OSDRC) and dry-coated tablets (DC).
AB  - One-step dry-coated tablets (OSDRC) were prepared using materials which are
      generally used in pharmaceutical tablets. The radial tensile strength of OSDRC
      was measured for various compression pressures and core porosities before the
      final compression to compare with that of conventional dry-coated tablets (DC).
      Furthermore, stress relaxation in the compression process was investigated.
      Radial tensile strength and stress relaxation profiles of OSDRC were the same as
      those of conventional DC. X-ray computerized tomography (CT) of the tablets
      showed that the density distribution of both tablets was also the same. Thus, we
      concluded that OSDRC and conventional DC have the same compression
      characteristics and physical properties. The OSDRC-system was executed by the use
      of upper and lower punches, which had a double structure, a center punch, and an
      outer punch surrounding the center punch. The OSDRC process consists of three
      compressions to make the lower-outer layer (1st-outer layer), the core, and the
      whole tablet including the upper-outer and side-outer layers (2nd-outer layer).
      At first, the powder for the 1st-outer layer fills a space, which is made by the
      lower-center punch and lower-outer punch, and is pre-compressed by the upper
      center punch. Then, while the upper-center punch pushes the pre-compressed 1st
      outer layer, the lower-center punch is slid down. The upper-center punch is then
      pulled away to make a space, which is filled with the powder for the core. This
      is then pre-compressed by the upper-center punch. Finally, the lower-outer punch
      is slid downward and the powder for the 2nd-outer layer fills and surrounds the
      pre-compressed core/1st-outer layer completely. The core/1st-outer layer and the
      2nd-outer layer complex is then compressed by the upper and lower punches in
      which the center punches are unified with the outer punches, respectively. This
      system can be assembled onto the turn table of a rotary tableting machine, and
      can make a dry-coated tablet in a single turn.

PMID- 12787638
TI  - Preparation of poly(DL-lactide-co-glycolide) microspheres encapsulating all-trans
      retinoic acid.
AB  - Poly(DL-lactide-co-glycolide) (PLGA) microspheres containing all-trans retinoic
      acid (atRA) were prepared by o/w solvent evaporation method and various
      preparation parameters, such as poly(vinyl alcohol) (PVA) concentration in
      aqueous solution, PVA MW, drug weight, solvent, polymer MW, and polymer weight,
      on the characteristics of microspheres and drug release were investigated. PVA
      concentration in water phase was a critical factor in making microspheres
      consistently with smooth surface and round shape. In our study, at least 2% (w/v)
      of PVA in aqueous solution was necessary for making microspheres with round
      shape. The particle size of microspheres ranged 10-100 microm. AtRA was slowly
      released from PLGA microspheres over 30 days. Sterilization of microspheres by
      ethylene oxide (EO) gas at 37 degrees C did not significantly affect the
      characteristics of drug release or its morphology. Cell growth inhibition of atRA
      was affected by preparation process of microspheres rather than the EO-gas
      sterilization process. These results indicate that PLGA microspheres containing
      atRA are acceptable for controlled release devices for use in the treatment of
      brain tumor.

PMID- 12787639
TI  - Nanoparticles bearing polyethyleneglycol-coupled transferrin as gene carriers:
      preparation and in vitro evaluation.
AB  - The aims of this work were to determine the stability of pDNA against various
      conditions during microencapsulation, prepare transferrin (TF)-conjugated
      PEGylated polycyanoacrylate nanoparticles (TF-PEG-nanoparticles), and assess its
      physicochemical characteristics and in vitro targeting cells association. The
      open circular forms of pDNA obviously increased when pDNA was emulsified into
      organic solution under sonification. When pDNA solution (pH 7.0) contained 1, 3
      or 5% (w/v) PVA, after sonification, average 48.2, 59.4 and 62.1% of double
      supercoiled DNA (dsDNA) were preserved, respectively. When medium of pDNA was
      0.9% NaCl (pH 7.0), 0.1M NaHCO(3) (pH 8.0) or phosphate buffer (pH 8.0), average
      53.1, 69.3 and 56.9% of dsDNA remained after sonification, respectively.
      Poly(aminopoly(ethylene glycol)cyanoacrylate-co-hexadecyl cyanoacrylate)
      (poly(H(2)NPEGCA-co-HDCA)) showed a slight influence on pDNA in 0.1M NaHCO(3) (pH
      8.0) when its concentration increased from 0.5 to 4% (w/v). TF-PEG-nanoparticles
      loading pDNA were spherical in shape with size under 200nm and entrapment
      efficiency 35-50%. 0.1M NaHCO(3) with 3% PVA (w/v) could largely reduce the
      damage of pDNA during microencapsulation. TF-PEG-nanoparticles bore 1-3% of the
      total PEG chains conjugated to TF molecules, and exhibited the burst effect with
      over 30% drug release within 1 day. After the first phase, pDNA release profiles
      displayed a sustained release. The amount of cumulated pDNA release over 7 days
      was: 86.3, 81.5 and 74.4% for 1, 2 and 4% polymer nanoparticles, respectively.
      The degree of target K562 cell binding of TF-PEG-nanoparticles was greater than
      that of non-targeted PEG-nanoparticles at 4 degrees C. The presence of free TF
      decreased significantly the degree of cell binding of TF-PEG-nanoparticles, which
      revealed that the binding of TF-PEG-nanoparticles to K562 cells was indeed
      receptor specific. These results suggested that TF-PEG-nanoparticles were useful
      for delivery of pDNA to target cells.

PMID- 12787640
TI  - Preparation of sustained-release nitrendipine microspheres with Eudragit RS and
      Aerosil using quasi-emulsion solvent diffusion method.
AB  - Sustained-release nitrendipine microspheres were prepared in liquid system by
      quasi-emulsion solvent diffusion method, in which the Aerosil was employed as an
      inert dispersing carrier to improve the dissolution rate of nitrendipine, and
      Eudragit RS as a retarding agent to control the release rate. The resultant
      microspheres were evaluated for the recovery, bulk density, average particle
      size, drug loading, and incorporation efficiency. And the factors affecting the
      formation of microspheres and the drug-release rate were investigated. It was
      observed by a scanning electron microscope (SEM) that the microspheres were
      finely spherical and uniform, and no entire nitrendipine crystals were observed
      visually. The results of X-ray diffraction indicated that nitrendipine in
      microspheres was disordered, suggesting that nitrendipine was highly dispersed in
      microspheres. The drug loading of microspheres was enhanced with increasing the
      ratio of drug to excipients, and the incorporation efficiency was always >90%.
      The formation of microspheres was mainly influenced by the amount of bridging
      liquid and sodium dodecyl sulfate (SDS) in poor solvent. The dissolution profiles
      could be modulated with adjusting the amount of retarding agent and dispersing
      carrier formulated.

PMID- 12787641
TI  - Effect of copolymer composition on the physicochemical characteristics, in vitro
      stability, and biodistribution of PLGA-mPEG nanoparticles.
AB  - The physicochemical properties, the colloidal stability in vitro and the
      biodistribution properties in mice of different PLGA-mPEG nanoparticle
      compositions were investigated. The nanoparticles were prepared by a
      precipitation-solvent evaporation technique. The physical characteristics and the
      colloidal stability of the PLGA-mPEG nanoparticles were significantly influenced
      by the composition of the PLGA-mPEG copolymer used to prepare the nanoparticles.
      PLGA-mPEG nanoparticles prepared from copolymers having relatively high mPEG/PLGA
      ratios were smaller and less stable than those prepared from copolymers having
      relatively low mPEG/PLGA ratios. All PLGA-mPEG nanoparticle compositions
      exhibited prolonged residence in blood, compared to the conventional PLGA
      nanoparticles. The composition of the PLGA-mPEG copolymer affected significantly
      the blood residence time and the biodistribution of the PLGA-mPEG nanoparticles
      in liver, spleen and bones. The in vivo behavior of the different PLGA-mPEG
      nanoparticle compositions did not appear to correlate with their in vitro
      stability. Optimum mPEG/PLGA ratios appeared to exist leading to long blood
      circulation times of the PLGA-mPEG nanoparticles. This may be associated with the
      effects of the mPEG/PLGA ratio on the density of PEG on the surface of the
      nanoparticles and on the size of the nanoparticles.

PMID- 12787642
TI  - Degradation kinetics of mometasone furoate in aqueous systems.
AB  - Mometasone furoate (MF) is a synthetic glucocorticoid. There is little
      information available on the stability of MF and no degradation products have
      been unequivocally identified. Thus, the primary objective of this study was to
      characterize the degradation of MF, qualitatively and quantitatively. Stability
      of MF decreased with increasing pH (>4) and decreasing ionic strength in aqueous
      media. The chemical stability of MF in aqueous systems was significantly
      dependent on pH. MF appeared to be stable at pH < 4 but degraded to four products
      at higher pH. The degradation of MF in aqueous solutions follows pseudo-first
      order kinetics and involved a series of parallel and consecutive reactions. The
      turnover of MF and its products appears to be catalyzed by the hydroxide ion. The
      pH dependence of these reactions should be considered, when formulating or
      extemporaneously compounding MF formulations. An optimal pH of stability was
      below pH 4. The changes in pH, however, do not appear to be the only factor of
      importance, since an increase in ionic strength and buffer concentration
      displayed a stabilizing effect on this glucocorticoid in the buffers tested.
      Trace metal ions are unlikely to be involved in degradation of MF in aqueous
      solution.

PMID- 12787643
TI  - Drug complexation, in vitro release and cellular entry of dendrimers and
      hyperbranched polymers.
AB  - Highly branched, functionalized polymers have potential to act as efficient drug
      carrier systems. Dendrimers are ideal candidates among model hyperbranched
      polymers because of their well-defined structure and high density of functional
      groups. Using ibuprofen as a model drug, we studied the interaction between the
      drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2
      functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with -
      OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly
      forms a complex with PAMAM dendrimers because of the ionic interaction between
      the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78
      molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2
      with 64 end groups. This complex is stable in deionized water and methanol. The
      in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower
      compared to pure ibuprofen. The complexed drug enters A549 cells much more
      rapidly than pure drug suggesting that dendrimers may be able to carry the
      complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end
      groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack
      of strong interactions between the --OH end groups and the drugs prevents complex
      formation.

PMID- 12787644
TI  - The preparation of agglomerates containing solid dispersions of diazepam by melt
      agglomeration in a high shear mixer.
AB  - The aim of this study was to prepare by melt agglomeration agglomerates
      containing solid dispersions of diazepam as poorly water-soluble model drug in
      order to evaluate the possibility of improving the dissolution rate. Lactose
      monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 or Gelucire
      50/13 (mixture of glycerides and PEG esters of fatty acids) as meltable binders
      in a high shear mixer. The binders were added either as a mixture of melted
      binder and diazepam by a pump-on procedure or by a melt-in procedure of solid
      binder particles. Different drug concentrations, maximum manufacturing
      temperatures, and cooling rates were investigated. It was found to be possible to
      increase the dissolution rate of diazepam by melt agglomeration. A higher
      dissolution rate was obtained with a lower drug concentration. Admixing the
      binders by the melt-in procedure resulted in similar dissolution rates as the
      pump-on procedure. The different maximum manufacturing temperatures and cooling
      rates were found to have complex effects on the dissolution rate for formulations
      containing PEG 3000, whereas only minor effects of the cooling procedure were
      found with Gelucire 50/13. Gelucire 50/13 resulted in faster dissolution rates
      compared to PEG 3000.

PMID- 12787645
TI  - Effect of hydrophilic polymers on the release of diltiazem hydrochloride from
      elementary osmotic pumps.
AB  - Diltiazem hydrochloride (DLTZ) is a freely water-soluble drug, because of its
      higher aqueous solubility, the suitability of the drug with elementary osmotic
      pumps is restricted. Plain DLTZ elementary osmotic pump had shown higher release
      rate. Drug entrapment in polymer matrix or addition of release retardant
      materials (various polymers) can reduce the release rate of drug. In present
      study, effect of appropriate hydrophilic polymers (HP) on the release pattern was
      investigated. Ingredients of the system were optimized for parameters like
      drug:polymer ratio and amount of osmogent, for the desired release pattern. Two
      optimized formulations were selected for further characterization. Theoretical
      release rate of the formulations were also determined and compared. Different
      dissolution models were applied to drug release data in order to establish
      release mechanism and kinetics. Criteria for selecting the most appropriate model
      were based on best goodness of fit and smallest sum of squared residuals.

PMID- 12787646
TI  - Fluorouracil prodrugs for the treatment of proliferative vitreoretinopathy:
      formulation in silicone oil and in vitro release of fluorouracil.
AB  - Three new N(1)-alkylcarbonyl-5-fluorouracil derivatives that are prodrugs of 5
      fluorouracil (FU), one of them being a co-drug FU-retinoic acid (RA), were
      studied as potentially effective drugs against postsurgical proliferative
      vitreoretinopathy (PVR). The stability of N(1)-octenoylFU (3), N(1)-lauroylFU
      (2), and N(1)-retinoylFU (4) in aqueous medium, their solubility in silicone oil
      (SiO), the kinetics of FU release in an in vitro system were determined. Compound
      3 is very rapidly soluble in SiO. Its saturation concentration, reached after 6h,
      is 233 +/- 13 microg g(-1) SiO. Compound 2 is not very soluble in SiO but its
      kinetic of solubilization is fast. Its saturation concentration, reached after 2
      days, is 27 +/- 2 microg g(-1) SiO. Compound 4 is poorly soluble in SiO. A
      concentration plateau, with a mean value of 4 microg g(-1) SiO, is reached after
      4 days. The addition in SiO of 5% of a perfluorinated perhydrogenated alkene
      greatly improves the solubilization of compound 4. Two different types of FU
      release are observed. For compound 3, the release is fast and is achieved after 1
      day. For compounds 2 and 4, the release is slower and is ended at 10 and 27 days,
      respectively. The solubility of the prodrugs in SiO is not correlated with their
      lipophilicity, whereas the release rate of FU decreased with increased
      lipophilicity of the prodrug. The most promising prodrug is compound 4 that
      slowly releases two active drugs (FU and RA) with a t (1/2 release) of 5.8 days.
      It might be interesting for the treatment of PVR. However, an in vivo study on an
      animal model of PVR is necessary to prove the efficacy of this formulation and to
      study its toxicity.

PMID- 12787647
TI  - Effect of 1-O-ethyl-3-butylcyclohexanol on the skin permeation of drugs with
      different physicochemical characteristics.
AB  - The effects of 1-O-ethyl-3-butylcyclohexanol (OEBC) on the in vitro skin
      permeation of ten model drugs with different physicochemical properties across
      excised rat skin were evaluated. The results showed that the addition of OEBC
      significantly improved the in vitro skin permeation of the model drugs compared
      with the control (without OEBC). To clarify the promoting mechanism of OEBC, a
      multiple regression analysis was employed. When the permeation study was
      performed without OEBC, the permeability coefficient was quantitatively predicted
      as a linear function of molecular weight (log MW) and their lipophilicity
      (partition coefficient of drugs between octanol and water (log K(o/w)) with a
      sufficiently high correlation coefficient (r=0.842). It was suggested that skin
      permeation of drugs without OEBC was explained as a function of diffusion of
      drugs through the skin and partitioning of drugs to the skin. Although OEBC was
      administered, the permeability coefficient of drugs cannot be predicted as a
      linear function of log MW and log K(o/w) (r=0.572).

PMID- 12787650
TI  - Study of unusual phenomenon of contact firing on gelatine block using .38 Special
      revolver--forensic importance.
AB  - Gunshot wounds in suicide cases are self-inflicted wounds. Self-inflicted wounds
      in suicide cases are usually caused by contact firing and are of great forensic
      significance. Evaluation of contact wound may be associated with difficulties if
      the bore gets obstruction prior to firing. This paper investigates the phenomenon
      and interprets the results of test firing conducted on 20% gelatine block at 10
      degrees C, using .38 Special revolver with obstruction of a bullet in the bore.
      Test firings were conducted in three different muzzle-target contact conditions
      keeping the muzzle pressed against the gel block in each case. The physical
      evidence and the wound ballistic parameter namely bullet track, remaining
      velocity of the bullets and volume of permanent cavity have been studied. When
      compared with the results of contact firing conducted with the same firearm
      without having any bore obstruction under similar conditions, it has been found
      that the physical evidence and the wound ballistic parameters would be helpful
      for interpretation of such unusual incidents for forensic inference.

PMID- 12787651
TI  - Organ weight effects of drowning and asphyxiation on the lungs, liver, brain,
      heart, kidneys, and spleen.
AB  - An examination of the organ weights associated with victims of drowning,
      asphyxiation and trauma was undertaken to determine (a) the effects of
      asphyxiation compared to a trauma group, and in turn, (b) the effects of drowning
      compared to an asphyxiation group. Included in the study were 217 drowning
      deaths, 166 pure asphyxiation deaths and 381 trauma deaths. The effects of
      asphyxiation (compared to trauma) resulted in elevated mean organ weights for the
      lungs, liver, kidneys and spleen (with mean increases of 17.8, 10.5, 10.3 and
      23.4%, respectively). Effects of drowning (compared to asphyxiation) resulted in
      elevated mean organ weights only with the lungs and kidneys (with mean increases
      of 30.0 and 4.4%, respectively). Only the mean heart and brain weight remained
      constant across all experimental groups. A picture of drowning is suggested in
      which elevated lung and kidney weights are the result of both asphyxiation and
      the aspiration of water that occurs with drowning, whereas elevated spleen and
      liver weights in drowning victims are associated with only the effects of
      asphyxiation. In addition, the common autopsy finding of a small, anemic spleen
      in drowning, rather than caused by some pathophysiological mechanism of death, is
      hypothesized to be a postmortem phenomenon.

PMID- 12787652
TI  - The violent female perpetrator and her victim.
AB  - The aim of the present study was to examine the relationship between violent
      female offenders and their victims as well as the putative differences in the
      motives and specific psychological factors among three groups of female
      offenders: women who have victimised someone closely related to them, those who
      have victimised an acquaintance and lastly women who have victimised a stranger.
      More than half (N=61) of all violent female offenders hospitalised or
      incarcerated in Finland during the year of study were interviewed and assessed by
      Structured Clinical Interview II for DSM-IV (SCID-II) and Hare's Psychopathy
      Checklist-Revised (PCL-R). In 34% of the cases the victims were persons close to
      the offender, in 41% the victims were acquaintances and in 25% strangers. The
      victims in homicide offences were more often both male and closer to the
      perpetrator than in assault offences. Although motives were related to
      interpersonal problems, self-defence and long-term physical or psychological
      abuse were reported by only a few women, even for the small proportion of women
      whose victims were intimate partners. The most frequent reason for offences
      stemmed from confrontational situations in connection with alcohol use. Women who
      victimised acquaintances and strangers were also more likely to have a history of
      criminality and substance abuse than women who victimised those in close personal
      relationships. The latter were also more likely to have an antisocial personality
      disorder (PD) and psychopathic characteristics. There were, however, no
      significant differences found between those who had experienced physical or
      psychological abuse in childhood or adulthood and those who had no adverse
      experiences. These findings suggest that the violent behaviour by females leads
      more often to the death of the victim, when the victim is closely related to the
      perpetrator. The commonly-held view that violent female offending occurs
      primarily as a consequence of precipitation by the victim was not supported.

PMID- 12787653
TI  - Area-specific increased density of mu-opioid receptor immunoreactive neurons in
      the cerebral cortex of drug-related fatalities.
AB  - In animal experiments and in cell culture, chronic morphine treatment has been
      followed by "up-regulation" as well as "down-regulation" of the mu-opioid
      receptor (OR) number. The present postmortem morphometric study of morphine
      related fatalities of drug-addicts (n=13, 20-35 years old, with blood
      unconjugated morphine levels from 27.1 ng/ml to 458 ng/ml, m.v. 198.5 ng/ml)
      versus a non-addicted control group (n=13, 10-44 years old) was intended to
      examine, whether chronic opiate exposure affects the numerical density of mu-OR
      expressing neurons in the human neocortex (areas 11, 24 and 25 according to
      Brodmann). For the immunohistochemical procedure, vibratome sections (100 microm)
      were incubated with a monoclonal antibody against the mu-OR, diluted 1:100, and
      immunolabelled sites were visualized using an immunoperoxidase protocol. The
      numerical densities of OR immunoreactive neuronal profiles and Nissl-stained
      central profiles were assessed morphometrically (camera lucida-drawings). In both
      groups, the anti-mu-OR-immunoreactivity was mainly localized in pyramidal neurons
      of layers (L) II/III and V and in multiform neurons of L VI. In the areas 24 and
      25, the density of the immunoreactive neuronal profiles did not display a
      significant difference between the two examined groups. In the area 11, however,
      the number of immunolabelled neuronal profiles amounted to 2777+/-206 mm(3) in
      the drug-related fatalities and to 2320+/-124 mm(3) in the control group and thus
      was significantly increased.

PMID- 12787654
TI  - Radiographic evaluation of third molar development in Spanish children and young
      people.
AB  - Third molar development was evaluated in 786 young people aged between 4 and 20
      years, all patients at the School of Dentistry of the University of Granada. The
      development of third molars and of mandibular second premolars and second molars
      was determined according to the stages proposed by Nolla. The onset of mandibular
      third molar formation was observed at very variable ages in this series, ranging
      from 5.86 to 14.66 years. The first developmental stages of maxillary third
      molars are not usually visible radiographically, which can lead to an incorrect
      diagnosis of agenesis. We found no significant relationship between the gender or
      age of the patient and the presence or absence of third molars. However, the
      presence/absence of the third molar can be predicted in 82.82% of cases when
      there is some degree of calcification of mandibular second molars and second
      premolars.

PMID- 12787655
TI  - Identification of a D8S1179 primer binding site mutation and the validation of a
      primer designed to recover null alleles.
AB  - A population study of Chamorros and Filipinos using short tandem repeat (STR)
      loci amplified with the AmpFlSTR Profiler Plus PCR amplification kit demonstrated
      an excess of observed homozygosity at the D8S1179 locus. Use of a different set
      of D8S1179 primers to type the same samples did not demonstrate an excess of
      homozygosity and showed discordant genotypes at the D8S1179 locus. A single point
      mutation, G-to-A transition, 16 nucleotides from the 3' end of the reverse
      primer, was identified to cause allele dropout when using the AmpFlSTR Profiler
      Plus primer set. An additional D8S1179 reverse primer specific for the variant
      was constructed resulting in the recovery of the null allele. The primer was
      included in the newly developed AmpFlSTR Identifiler PCR amplification kit. No
      deleterious effects or non-specific peaks were observed in validation experiments
      evaluating primer concentration, Mg2+ concentration, annealing temperature and
      population samples.

PMID- 12787656
TI  - Response of short tandem repeat systems to temperature and sizing methods.
AB  - In capillary gel electrophoresis (CE), changing run conditions such as
      temperature can result in minor variations in the size determination of an
      allele. These effects are caused by secondary structure differences that can
      occur between the amplified sample and the internal standard. The type of method
      chosen to generate the sizing curve in STR analysis can influence the
      relationship between estimated allele size and temperature. To better understand
      the effects of temperature and sizing method on the reproducibility of DNA
      migration, two fluorescently labeled allelic ladders, CTTv and Y-PLEX 6 were
      analyzed using the ABI Prism 310 Genetic Analyzer. The default method on the
      Genetic Analyzer utilizes an electrophoretic temperature of 60 degrees C and a
      Local Southern method to generate a sizing curve from the fragment migration
      times of the internal lane standard. In this work, electrophoresis was conducted
      at 35-70 degrees C using the commercially available POP 4 buffer at pH 8 and two
      sizing methods, Global Southern and Local Southern, were compared. The slopes of
      the regression line between estimated allele size and temperature, using either
      sizing method, were measured in order to demonstrate the temperature sensitivity
      of migration time and the importance of the operator-chosen method. Our results
      indicate that the Global Southern method is a better choice in situations where
      temperature fluctuations can occur. In addition, the temperature dependence of
      the DNA size estimates using the POP 4 system were compared to results obtained
      using an experimental buffer consisting of 3% hydroxyethylcellulose at pH 11.
      These results demonstrate that secondary structure effects are minimized at an
      elevated pH, increasing the precision of size estimates obtained.

PMID- 12787657
TI  - Mitochondrial profiling of dog hairs.
AB  - In order to make greater use of dog hairs as forensic evidence, we have developed
      a robust method for duplex amplification of adjacent 306 and 332bp amplicons
      within the 5' hypervariable region (5' HVR) of the canine mitochondrial control
      region. In support of this, a 595bp region covering 35 polymorphic sites has been
      sequenced from the blood of 105 UK dogs. In total, 30 different haplotypes were
      observed, 13 only once whilst the commonest was seen 14 times; the overall
      exclusion capacity is 0.929. One animal was heteroplasmic in blood for a single
      base deletion and showed phenotypes ranging from near complete deletion to a
      predominance of the base among a sample of 12 hairs. In contrast, no evidence of
      heteroplasmy was seen in single hairs from 20 dogs which were not visibly
      heteroplasmic in blood. Phylogenetic analysis and comparisons with other
      published databases highlighted instances of possible recurrent mutation which
      may be relevant when interpreting single base differences between samples.

PMID- 12787658
TI  - Single-strand conformation polymorphism of hyper-variable regions HV1 and HV2 of
      human mitochondrial DNA: detection by silver staining.
AB  - Human mitochondrial DNA from 50 trios consisting of mother (M), child (C) and
      father (F) was PCR amplified with primers flanking the hyper-variable regions,
      HVR1 and HVR2. The amplified products were then fractionated under non-denaturing
      conditions, silver-stained and compared by single-stranded conformational
      polymorphism (SSCP). In all but one case, mother and child displayed identical
      patterns, which could be promptly distinguished from that of the father. For the
      remaining cases, either set of primers was sufficient to resolve the familial
      ties. In no instance, M displayed alleles different from those of C within each
      trio, demonstrating that no false exclusions occurred. The SSCP approach proved
      to be a robust technique suitable as a preliminary screening in cases requiring
      identification of multiple samples.

PMID- 12787659
TI  - Development of the X-linked tetrameric microsatellite markers HumDXS6803 and
      HumDXS9895 for forensic purpose.
AB  - This paper presents sequence and population genetic data of the X-linked DXS6803
      and DXS9895 short tandem repeat (STR). The tetranucleotide repeat polymorphism
      DXS6803 (also known as CHLC.GATA45H11) and DXS9895 (also known as
      CHLC.GATA124B04) are located at the Xq12-Xq21.33 and Xpter-Xp22.2 region,
      respectively. In kinship testing, DXS6803 and DXS9895 are suitable for
      concomitant use. Population genetic data were obtained by analyzing 182 unrelated
      females and 110 males from Chinese Han population. In this population, both
      DXS6803 and DXS9895 exhibited seven clearly distinguishable alleles ranging from
      109bp to 128bp and 139bp to 163bp in length, respectively. Testing for Hardy
      Weinberg equilibrium (HWE) showed no significant deviation for these two loci.
      The polymorphism information content (PIC), observed heterozygosity (H(obs)) and
      power of exclusion for parentage testing of a girl for trios (PE(trio)) and duos
      (PE(duo)) were 0.67, 0.687, 0.673 and 0.530 for DXS6803, and 0.69, 0.736, 0.688
      and 0.547 for DXS9895, respectively. Seventy-eight families studies of these two
      loci confirmed X-linked codominant inheritance and mutations were not found.

PMID- 12787660
TI  - Polymorphism of 17 STRs by multiplex analysis in Japanese population.
AB  - Genotype and distribution of allele frequencies at 17 STRs were studied in 526
      unrelated Japanese individuals using the PowerPlex 16 system and the AmpFlSTR
      Identifiler.

PMID- 12787661
TI  - Genetic data on 11 STRs (CSF1PO, TPOX, TH01, F13A01, FESFPS, vWA, D16S539,
      D7S820, D13S317, F13B, LPL) in an Argentine northeast population.
AB  - Allele frequencies for 11 short tandem repeats (STRs) loci (CSF1PO, TPOX, TH01,
      F13A01, FESFPS, vWA, D16S539, D7S820, D13S317, F13B and LPL) were obtained from a
      sample of 225 unrelated individuals born in the Entre Rios state of Argentina.

PMID- 12787662
TI  - Intoxication due to 1,4-butanediol.
AB  - We report a case of intoxication resulting from the ingestion of a liquid, sold
      in the illicit market as "liquid ecstasy," which was found to contain 1,4
      butanediol, a metabolic precursor of gamma-hydroxybutiric acid (GHB).
      Identification of the substance in the liquid was performed by gas chromatography
      mass spectrometry (GC-MS). The toxicological analysis of blood, urine and gastric
      content of the victim was performed by immunoassay and gas chromatography with
      nitrogen-phosphorus detection as screening techniques and by means of GC-MS for
      confirmation and quantitation of 1,4-butanediol and GHB. The following drug
      concentrations were found: 82 microg/ml (blood), 401 microg/ml (urine) and 7.4
      microg/ml (gastric content) for 1,4-butanediol and 103 microg/ml (blood), 430.0
      microg/ml (urine) for GHB. In addition to these, other drugs detected and their
      blood concentration found in this case were methylenedioxymethylamphetamine
      (MDMA) 0.23 microg/ml and its metabolite methylenedioxyphenylamphetamine (MDA)
      0.10 microg/ml. In the urine, a concentration of 0.10 microg/ml of
      benzoylecgonine was also found.

PMID- 12787663
TI  - Inferring recent human phylogenies using forensic STR technology.
AB  - STR loci are characterized by extremely high mutation rates and thus, high levels
      of length polymorphism both within and among populations. In addition, much of
      the observed variation is believed to be nearly selectively neutral. Because of
      these features, STRs are ideal markers for genetic mapping, intra-species
      phylogenetic reconstructions and forensic analysis. In the present study, we
      investigate the application of five STR loci (CS1PO, TH01, TPOX, FGA and vWA)
      routinely used in forensic analysis for delineating the phylogenetic
      relationships of 10 human populations representing the three major racial groups
      (African-Caribbean, Croatian from the island of Hvar, East Asian, Han Chinese,
      Italian, Japanese, Portuguese, UK Caucasian, US Caucasian and Zimbabwe). The
      resulting tree topology exhibited strong geographic and racial partitioning
      consistent with that obtained with mtDNA haplotypes, Y-chromosome markers, SNPs,
      PAIs (polymorphic Alu insertions) as well as classic genetic polymorphisms. These
      findings suggest that forensic STR loci may be particularly powerful tools and
      provide the necessary fine resolution for the reconstruction of recent human
      evolutionary history.

PMID- 12787664
TI  - Experimental tests of villin subdomain folding simulations.
AB  - We have used laser temperature-jump to investigate the kinetics and mechanism of
      folding the 35 residue subdomain of the villin headpiece. The relaxation kinetics
      are biphasic with a sub-microsecond phase corresponding to a helix-coil
      transition and a slower microsecond phase corresponding to overall
      unfolding/refolding. At 300 K, the folding time is 4.3(+/-0.6) micros, making it
      the fastest folding, naturally occurring protein, with a rate close to the
      theoretical speed limit. This time is in remarkable agreement with the prediction
      of 5 (+11,-3) micros by Zagrovic et al. from atomistic molecular dynamics
      simulations using an implicit solvent model. We test their prediction that
      replacement of the C-terminal phenylalanine residue with alanine will increase
      the folding rate by removing a transient non-native interaction. We find that the
      alanine substitution has no effect on the folding rate or on the equilibrium
      constant. Implications of this result for the validity of the simulated folding
      mechanism are discussed.

PMID- 12787665
TI  - Functional domains of FOXJ2.
AB  - FOXJ2 is a fork head transcriptional activator, the expression of which starts
      very early in embryonic development and it is distributed widely in the adult.
      Here, we describe the characterization of domains that are important for its
      function. FOXJ2 is localized constitutively at the nucleus of the cell. Two
      tyrosine residues and a stretch of basic amino acid residues at the N and C
      terminal ends of the fork head domain, respectively, are important for its
      nuclear targeting. These residues are conserved strongly among all members of the
      fork head family, suggesting that they could be involved in the nuclear
      translocation mechanism of all fork head factors. In addition to the AB domain,
      we have found, at least, two other transactivation domains: Domain I, at the N
      terminus, and the H/P domain, rich in histidine and proline residues. Although
      the AB domain shows the strongest transactivation capacity, all three domains are
      required for full FOXJ2 transcriptional activity. Furthermore, a fourth region
      rich in proline and glutamine residues and with no intrinsic transactivation
      function, the P/Q domain, appears to play an important role in the FOXJ2-mediated
      transactivation mechanism. Although FOXJ2 can be phosphorylated in two serine
      residues, this post-translational modification did not appear to be essential for
      transactivation. Finally, we have found that the W2 wing of the fork head domain
      of FOXJ2 is dispensable for specific DNA binding, although it could have a weak
      stabilizing role for the DNA-FOXJ2 complex.

PMID- 12787666
TI  - Response delays and the structure of transcription networks.
AB  - Sensory transcription networks generally control rapid and reversible gene
      expression responses to external stimuli. Developmental transcription networks
      carry out slow and irreversible temporal programs of gene expression during
      development. It is important to understand the design principles that underlie
      the structure of sensory and developmental transcription networks. Cascades,
      which are chains of regulatory reactions, are a basic structural element of
      transcription networks. When comparing databases of sensory and developmental
      transcription networks, a striking difference is found in the distribution of
      cascade lengths. Here, we suggest that delay times in the responses of the
      network present a design constraint that influences the network architecture. We
      experimentally studied the response times in simple cascades constructed of well
      characterized repressors in Escherichia coli. Accurate kinetics at high temporal
      resolution was measured using green fluorescent protein (GFP) reporters. We find
      that transcription cascades can show long delays of about one cell-cycle time per
      cascade step. Mathematical analysis suggests that such a delay is characteristic
      of cascades that are designed to minimize the response times for both turning-on
      and turning-off gene expression. The need to achieve rapid reversible responses
      in sensory transcription networks may help explain the finding that long cascades
      are very rare in databases of E.coli and Saccharomyces cerevisiae sensory
      transcription networks. In contrast, long cascades are common in developmental
      transcription networks from sea urchin and from Drosophila melanogaster. Response
      delay constraints are likely to be less important for developmental networks,
      since they control irreversible processes on the timescale of cell-cycles. This
      study highlights a fundamental difference between the architecture of sensory and
      developmental transcription networks.

PMID- 12787667
TI  - Role of E.coli transcription-repair coupling factor Mfd in Nun-mediated
      transcription termination.
AB  - Phage HK022 Nun protein excludes phage lambda by binding nascent lambda-nut RNA
      and inducing termination and transcript release. In contrast, in a purified in
      vitro system, Nun arrests transcription on lambdaDNA templates without
      dissociation of the transcription elongation complex (TEC). Our evidence
      indicates that transcription-repair coupling factor (Mfd) frees Nun-arrested RNA
      polymerase. The activity of Nun is enhanced in an mfd-null mutant, consistent
      with prolonged association of Nun with the TEC. Furthermore, expression of lambda
      nut RNA in the mfd mutant titrates Nun, allowing superinfecting lambda to form
      plaques. Finally, addition of Mfd releases a Nun-arrested transcription complex
      in vitro.

PMID- 12787668
TI  - Protein feature based identification of cell cycle regulated proteins in yeast.
AB  - DNA microarrays have been used extensively to identify cell cycle regulated genes
      in yeast; however, the overlap in the genes identified is surprisingly small. We
      show that certain protein features can be used to distinguish cell cycle
      regulated genes from other genes with high confidence (features include protein
      phosphorylation, glycosylation, subcellular location and
      instability/degradation). We demonstrate that co-expressed, periodic genes encode
      proteins which share combinations of features, and provide an overview of the
      proteome dynamics during the cycle. A large set of novel putative cell cycle
      regulated proteins were identified, many of which have no known function.

PMID- 12787669
TI  - Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: covalent
      intermediate formation is not essential for methyl group transfer by the murine
      Dnmt3a enzyme.
AB  - Co-transfections of reporter plasmids and plasmids encoding the catalytic domain
      of the murine Dnmt3a DNA methyltransferase lead to inhibition of reporter gene
      expression. As Dnmt3a mutants with C-->A and E-->A exchanges in the conserved PCQ
      and ENV motifs in the catalytic center of the enzyme also cause repression, we
      checked for their catalytic activity in vitro. Surprisingly, the activity of the
      cysteine variant and of the corresponding full-length Dnmt3a variant is only two
      to sixfold reduced with respect to wild-type Dnmt3a. In contrast, enzyme variants
      carrying E-->A, E-->D or E-->Q exchanges of the ENV glutamate are catalytically
      almost inactive, demonstrating that this residue has a central function in
      catalysis. Since the glutamic acid residue contacts the flipped base, its main
      function could be to hold the target base at a position that supports methyl
      group transfer. Whereas wild-type Dnmt3a and the ENV variants form covalent
      complexes with 5-fluorocytidine modified DNA, the PCN variant does not.
      Therefore, covalent complex formation is not essential in the reaction mechanism
      of Dnmt3a. We propose that correct positioning of the flipped base and the
      cofactor and binding to the transition state of methyl group transfer are the
      most important roles of the Dnmt3a enzyme in the catalytic cycle of methyl group
      transfer.

PMID- 12787670
TI  - Crystallographic characterization of an exocyclic DNA adduct: 3,N4-etheno-2'
      deoxycytidine in the dodecamer 5'-CGCGAATTepsilonCGCG-3'.
AB  - Exocyclic DNA adducts are formed from metabolites of chemical carcinogens and
      have also been detected as endogenous lesions in human DNA. The exocyclic adduct
      3,N(4)-etheno-2'-deoxycytidine (epsilon dC), positioned opposite deoxyguanosine
      in the B-form duplex of the dodecanucleotide d(CGCGAATTepsilonCGCG), has been
      crystallographically characterized at 1.8A resolution. This self-complementary
      oligomer crystallizes in space group P3(2)12, containing a single strand in the
      asymmetric unit. The crystal structure was solved by isomorphous replacement with
      the corresponding unmodified dodecamer structure. Exposure of both structures to
      identical crystal packing forces allows a detailed investigation of the influence
      of the exocyclic base adduct on the overall helical structure and local geometry.
      Structural changes are limited to the epsilon C:G and adjacent T:A and G:C base
      pairs. The standard Watson-Crick base-pairing scheme, retained in the T:A and G:C
      base-pairs, is blocked by the etheno bridge in the epsilon C:G pair. In its
      place, a hydrogen bond involving O2 of epsilon C and N1 of G is present.
      Comparison with an epsilon dC-containing NMR structure confirms the general
      conformation reported for epsilon C:G, including the hydrogen bonding features.
      Superposition with the crystal structure of a DNA duplex containing a T:G wobble
      pair shows similar structural changes imposed by both mismatches. Evaluation of
      the hydration shell of the duplex with bond valence calculations reveals two
      sodium ions in the crystal.

PMID- 12787671
TI  - Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and
      p120GAP.
AB  - Ras specific GTPase activating proteins (GAPs), neurofibromin and p120GAP, bind
      GTP bound Ras and efficiently complement its active site. Here we present
      comparative data from mutations and fluorescence-based assays of the catalytic
      domains of both RasGAPs and interpret them using the crystal structures. Three
      prominent regions in RasGAPs, the arginine-finger loop, the phenylalanine-leucine
      arginine (FLR) region and alpha7/variable loop contain structural fingerprints
      governing the GAP function. The finger loop is crucial for the stabilization of
      the transition state of the GTPase reaction. This function is controlled by
      residues proximal to the catalytic arginine, which are strikingly different
      between the two RasGAPs. These residues specifically determine the orientation
      and therefore the positioning of the arginine finger in the Ras active site. The
      invariant FLR region, a hallmark for RasGAPs, indirectly contributes to GTPase
      stimulation by forming a scaffold, which stabilizes Ras switch regions. We show
      that a long hydrophobic side-chain in the FLR region is crucial for this
      function. The alpha7/variable loop uses several conserved residues including two
      lysine residues, which are involved in numerous interactions with the switch I
      region of Ras. This region determines the specificity of the Ras-RasGAP
      interaction.

PMID- 12787672
TI  - Compositional heterogeneity reflects partial dehydration in three-dimensional
      crystals of bacteriorhodopsin.
AB  - Absorption, fluorescence and excitation spectra of three-dimensional
      bacteriorhodopsin crystals harvested from a lipidic cubic phase are presented.
      The combination of the spectroscopic experiments performed at room temperature,
      controlled pH and full external hydration reveals the presence of three distinct
      protein species. Besides the well-known form observed in purple membrane, we find
      two other species with a relative contribution of up to 30%. As the spectra are
      similar to those of dehydrated or deionized membranes containing
      bacteriorhodopsin, we suggest that amino acid residues, located in the vicinity
      of the retinal chromophore, have changed their protonation state. We propose
      partial dehydration during crystallization and/or room temperature conditions as
      the main source of this heterogeneity. This assignment is supported by an
      experiment showing interconversion of the species upon intentional dehydration
      and by crystallographic data, which have indicated an in-plane unit cell in 3D
      crystals comparable to that of dehydrated bacteriorhodopsin membranes. Full
      hydration of the proteins after the water-withdrawing crystallization process is
      hampered. We suggest that this hindered water diffusion originates mainly from a
      closure of hydrophobic crystal surfaces by lipid bilayers. The present
      spectroscopic work complements the crystallographic data, due to its ability to
      determine quantitatively compositional heterogeneity resulting from proteins in
      different protonation states.

PMID- 12787673
TI  - Plant-based heterologous expression of Mal d 2, a thaumatin-like protein and
      allergen of apple (Malus domestica), and its characterization as an antifungal
      protein.
AB  - Mal d 2 is a thaumatin-like protein and important allergen of apple fruits that
      is associated with IgE-mediated symptoms in apple allergic individuals. We
      obtained a full-length cDNA clone of Mal d 2 from RNA isolated from ripe apple
      (Malus domestica cv. Golden Delicious). The cDNA's open reading frame encodes a
      protein of 246 amino acid residues including a signal peptide of 24 residues and
      two putative glycosylation sites. The deduced amino acid sequence of the mature
      Mal d 2 protein results in a predicted molecular mass of 23,210.9Da and a
      calculated pI of 4.55. Sequence comparisons and molecular modeling place Mal d 2
      among those pathogenesis-related thaumatin-like proteins that contain a conserved
      acidic cleft. In order to ensure the correct formation of the protein's eight
      conserved disulfide bridges we expressed Mal d 2 in Nicotiana benthamiana plants
      by the use of a tobacco mosaic viral vector. Transfected N.benthamiana plants
      accumulated Mal d 2 to levels of at least 2% of total soluble protein. MALDI-TOF
      mass spectrometric analyses of the recombinant Mal d 2 and its proteolytic
      fragments showed that the apple-specific leader peptide was correctly cleaved off
      by the host plant and that the mature recombinant protein was intact and not
      glycosylated. Purified recombinant Mal d 2 displayed the ability to bind IgE from
      apple-allergic individuals equivalent to natural Mal d 2. In addition, the
      recombinant thaumatin-like Mal d 2 exhibited antifungal activity against Fusarium
      oxysporum and Penicillium expansum, implying a function in plant defense against
      fungal pathogens.

PMID- 12787674
TI  - Energetic evidence for formation of a pH-dependent hydrophobic cluster in the
      denatured state of Thermus thermophilus ribonuclease H.
AB  - NMR studies on the denatured states of proteins indicate that residual structure
      often resides predominantly in hydrophobic clusters. Such hydrophobic cluster
      formation implies burial of apolar surface and, consequently, is expected to
      cause a decrease in heat capacity. We report here that, in the case of
      ribonuclease H from the thermophile Thermus thermophilus, a sharp decrease in
      denatured-state heat capacity occurs at about pH 3.8; this result points to the
      formation of hydrophobic clusters triggered by the protonation of several (about
      four) carboxylic acid groups, and indicates that the burial of apolar surface is
      favored by the less hydrophilic character of the uncharged forms of Asp and Glu
      side-chains. The process is not accompanied by large changes in optically active
      structure, but appears to be highly cooperative, as indicated by the sharpness of
      the pH-induced transition in the heat capacity. This acid-induced hydrophobic
      burial in denatured T.thermophilus ribonuclease H is clearly reflected in the pH
      dependence of the denaturation temperature (i.e. an abrupt change of slope at
      about pH 3.8 is seen in the plot of denaturation temperature versus pH),
      supporting a role for such denatured-state hydrophobic clusters in protein
      stability. The finding of cooperative protonation of several groups coupled to
      surface burial in denatured T.thermophilus ribonuclease H emphasizes the
      potential complexity of denatured-state electrostatics and advises caution when
      attempting to predict denatured-state properties on the basis of simple
      electrostatic models. Finally, our results suggest a higher propensity for
      hydrophobic cluster formation in the denatured state of T.thermophilus
      ribonuclease H as compared with that of its mesophilic counterpart from
      Escherichia coli.

PMID- 12787675
TI  - Structure, stability and dynamics of the central domain of cardiac myosin binding
      protein C (MyBP-C): implications for multidomain assembly and causes for
      cardiomyopathy.
AB  - The large multidomain muscle protein myosin binding protein C (MyBP-C) has been
      implicated for some time in cardiac disease while until recently little was known
      about its structure and function. Here we present a detailed study of the central
      domain C5 of the cardiac isoform of MyBP-C. This domain is unusual in several
      aspects. Firstly it contains two sizeable insertions compared to the non-cardiac
      isoforms. The first insertion comprises the linker between domains cC4 and cC5
      that is elongated by ten amino acid residues, the second insertion comprises an
      elongation of the CD-loop in the middle of the domain by approximately 30 amino
      acid residues. Secondly two point mutations linked to familial hypertrophic
      cardiomyopathy (FHC) have been identified in this domain. This work shows that
      the general fold of cC5 is in agreement with the IgI family of beta-sandwich
      structures. The long cardiac-specific linker between cC4 and cC5 is not a linker
      at all but an integral part of the fold of cC5, as evidenced by an unfolded
      mutant in which this segment was removed. The second insertion is shown to be
      unstructured, highly dynamic and mostly extended according to NMR relaxation
      measurements and analytical ultracentrifugation. The loss of several key
      interactions conserved in the CD-loop of the IgI fold is assumed to be
      responsible for the low stability of cC5 compared to other IgI domains from titin
      and MyBP-C itself. The low thermodynamic stability of cC5 is most evident in one
      of the two FHC-linked mutations, N755K (Asn115 in this construct) which is mainly
      unfolded with a small proportion of a native-like folded species. In contrast,
      the second FHC-linked mutation, R654H (Arg14 in this construct) is as well folded
      and stable as the wild-type. This residue is located in the extended beta-bulge
      at the N terminus of the protein, pointing towards the surface of the CFGA' beta
      sheet. This position is in agreement with recent data pointing to a function of
      Arg654 in an intermolecular interaction with MyBP-C domain cC8.

PMID- 12787676
TI  - A structural and functional role for 11-mer repeats in alpha-synuclein and other
      exchangeable lipid binding proteins.
AB  - We have used NMR spectroscopy and limited proteolysis to characterize the
      structural properties of the Parkinson's disease-related protein alpha-synuclein
      in lipid and detergent micelle environments. We show that the lipid or micelle
      surface-bound portion of the molecule adopts a continuously helical structure
      with a single break. Modeling alphaS as an ideal alpha-helix reveals a
      hydrophobic surface that winds around the helix axis in a right-handed fashion.
      This feature is typical of 11-mer repeat containing sequences that adopt right
      handed coiled coil conformations. In order to bind a flat or convex lipid
      surface, however, an unbroken helical alphaS structure would need to adopt an
      unusual, slightly unwound, alpha11/3 helix conformation (three complete turns per
      11 residues). The break we observe in the alphaS helix may allow the protein to
      avoid this unusual conformation by adopting two shorter stretches of typical
      alpha-helical structure. However, a quantitative analysis suggests the
      possibility that the alpha11/3 conformation may in fact exist in lipid-bound
      alphaS. We discuss how structural features of helical 11-mer repeats could play a
      role in the reversible lipid binding function of alpha-synuclein and generalize
      this argument to include the 11-mer repeat-containing apolipoproteins, which also
      require the ability to release readily from lipid surfaces. A search of protein
      sequence databases confirms that synuclein-like 11-mer repeats are present in
      other proteins that bind lipids reversibly and predicts such a role for a number
      of hypothetical proteins of unknown function.

PMID- 12787677
TI  - Effects of the difference in the unfolded-state ensemble on the folding of
      Escherichia coli dihydrofolate reductase.
AB  - The unfolded state of a protein is an ensemble of a large number of conformations
      ranging from fully extended to compact structures. To investigate the effects of
      the difference in the unfolded-state ensemble on protein folding, we have studied
      the structure, stability, and folding of "circular" dihydrofolate reductase
      (DHFR) from Escherichia coli in which the N and C-terminal regions are cross
      linked by a disulfide bond, and compared the results with those of disulfide
      reduced "linear" DHFR. Equilibrium studies by circular dichroism, difference
      absorption spectra, solution X-ray scattering, and size-exclusion chromatography
      show that whereas the native structures of both proteins are essentially the
      same, the unfolded state of circular DHFR adopts more compact conformations than
      the unfolded state of the linear form, even with the absence of secondary
      structure. Circular DHFR is more stable than linear DHFR, which may be due to the
      decrease in the conformational entropy of the unfolded state as a result of
      circularization. Kinetic refolding measurements by stopped-flow circular
      dichroism and fluorescence show that under the native conditions both proteins
      accumulate a burst-phase intermediate having the same structures and both fold by
      the same complex folding mechanism with the same folding rates. Thus, the effects
      of the difference in the unfolded state of circular and linear DHFRs on the
      refolding reaction are not observed after the formation of the intermediate. This
      suggests that for the proteins with close termini in the native structure, early
      compaction of a protein molecule to form a specific folding intermediate with the
      N and C-terminal regions in close proximity is a crucial event in folding. If
      there is an enhancement in the folding reflecting the reduction in the breadth of
      the unfolded-state ensemble for circular DHFR, this acceleration must occur in
      the sub-millisecond time-range.

PMID- 12787678
TI  - The sensitivity of lipid domains to small perturbations demonstrated by the
      effect of Triton.
AB  - The hypothesis of lipid rafts describes functional domains in biological
      membranes. It is often assumed that rafts form by spontaneous de-mixing of
      certain lipids and that they can be isolated as detergent-resistant membrane
      particles (DRMs) using the detergent Triton X-100 (TX). Here, we present a model
      that describes the process of domain formation in membranes in the presence and
      in the absence of TX. We measure the interactions between TX and an equimolar
      mixture of sphingomyelin (SM), cholesterol (Cho), and 1-palmitoyl-2-oleoyl-3-sn
      glycero-phosphatidylcholine (POPC) (1:1:1, mol) by means of isothermal titration
      calorimetry. Comparison with pure POPC membranes reveals a very unfavorable
      interaction between TX and SM/Cho, which causes a substantial tendency to
      segregate these molecules into separate, DRM-like (SM-rich) and fluid (TX-rich),
      domains. If rafts are indeed formed by spontaneous de-mixing of PC and SM/Cho,
      they must be very sensitive, and perturbations caused by techniques used to study
      rafts could lead to misleading results. If, however, rafts are much more stable
      than PC-SM-Cho domains, there must be an unknown raft stabilizer. Subtle changes
      of such a promoter could serve to modulate raft function.

PMID- 12787679
TI  - Structure-based analysis of GPCR function: conformational adaptation of both
      agonist and receptor upon leukotriene B4 binding to recombinant BLT1.
AB  - We produced the human leukotriene B(4) (LTB(4)) receptor BLT1, a G-protein
      coupled receptor, in Escherichia coli with yields that are sufficient for the
      first structural characterization of this receptor in solution. Overexpression
      was achieved through codon optimization and the search for optimal refolding
      conditions of BLT1 recovered from inclusion bodies. The detergent-solubilized
      receptor displays a 3D-fold compatible with a seven transmembrane (TM) domain
      with ca 50% alpha-helix and an essential disulfide bridge (circular dichroism
      evidence); it binds LTB(4) with K(a)=7.8(+/-0.2)x10(8)M(-1) and a stoichiometric
      ratio of 0.98(+/-0.02). Antagonistic effects were investigated using a synthetic
      molecule that shares common structural features with LTB(4). We report evidence
      that both partners, LTB(4) and BLT1, undergo a rearrangement of their respective
      conformations upon complex formation: (i) a departure from planarity of the
      LTB(4) conjugated triene moiety; (ii) a change in the environment of Trp234 (TM
      VI helix) and in the exposure of the cytoplasmic region of this transmembrane
      helix.

PMID- 12787680
TI  - Structure-based analysis of GPCR function: evidence for a novel pentameric
      assembly between the dimeric leukotriene B4 receptor BLT1 and the G-protein.
AB  - We produced human leukotriene B(4) (LTB(4)) receptor BLT1 as a recombinant
      protein in Escherichia coli. This detergent-solubilized receptor displays two
      states with regard to its affinity for LTB(4): (i) a low-affinity state
      (K(a)=7.8x10(8)M(-1)) that involves a receptor homodimer (BLT1.LTB(4))(2); we
      report evidence for a central role of the sixth transmembrane helix in regulating
      the stability of this homodimer; (ii) a high-affinity state (K(a)=1.3x10(10)M(
      1)) upon interaction of the receptor with the heterotrimeric GDP-loaded G
      protein, Galpha(i2)beta(1)gamma(2). Association of the G-protein with recombinant
      BLT1 induces GDP-GTP exchange by the Galpha subunit. These results indicate that
      isolated BLT1 is fully representative of the in vivo receptor with regard to high
      affinity recognition of LTB(4), association with a G-protein and activation of
      Galpha. Using a combination of mass spectrometry after chemical cross-linking and
      neutron-scattering in solution with the native complex, we establish
      unambiguously that only one G-protein trimer binds to a receptor dimer to form
      the stoichiometrically defined (BLT1.LTB(4))(2):Galpha(i2)beta(1)gamma(2)
      pentameric assembly. This suggests that receptor dimerization could be crucial to
      transduction of the LTB(4)-induced signal.

PMID- 12787681
TI  - A simple method for modeling transmembrane helix oligomers.
AB  - We describe an effective procedure for modeling the structures of simple
      transmembrane helix homo-oligomers. The method differs from many previous
      approaches in that the only structural constraint we use to help select the
      correct model is the oligomerization state of the protein. The method involves
      the following steps: (1) perform 100-250 independent Monte Carlo energy
      minimizations of helix pairs to produce a large collection of well-packed
      structures; (2) filter the minimized structures to find those that are consistent
      with the expected symmetry of the oligomer; (3) cluster the structures that pass
      the symmetry filter; and (4) select a representative of the most populous cluster
      as the final prediction. We applied the method to the transmembrane helices of
      five proteins and compare our results to the available experimental data. Our
      predictions of glycophorin A, neu, the M2 channel and phospholamban resulted in a
      single model for each protein that agreed with the experimental results. In the
      case of erbB-2, however, we obtained three structurally distinct clusters of
      approximately equal sizes, so it was not possible to identify a clearly favored
      structure. This may reflect a real heterogeneity of packing modes for erbB-2,
      which is known to interact with different receptor subunits. Our method should be
      useful for obtaining structural models of transmembrane domains, improving our
      understanding of structure/function relationships for particular membrane
      proteins.

PMID- 12787682
TI  - High-resolution structures of retinol-binding protein in complex with retinol: pH
      induced protein structural changes in the crystal state.
AB  - The targeted delivery of non-polar ligands by binding proteins to membranes or
      membrane receptors involves the release of these ligands on or near the plasma
      membrane of target cells. Because these hydrophobic ligands are often bound
      inside a deep cavity of binding proteins, as shown previously for plasma retinol
      binding protein (RBP), their release from these proteins might require the
      destabilization of the protein structure by partially denaturing conditions, such
      as those possibly present near plasma membranes. RBP is a plasma transport
      protein which delivers specifically retinol from its store sites to target cells.
      Here, we report the high-resolution (1.1-1.4A) crystal structures of bovine holo
      RBP at five different pH values, ranging from 9 to 2. While unraveling details of
      the native protein structure and of the interactions with retinol at nearly
      atomic resolution at neutral pH, this study provides evidence for definite pH
      induced modifications of several structural features of RBP. The structure most
      representative of the changes that holo-RBP undergoes at different pH values is
      that of its flexible state at pH 2. At this pH, most significant are the
      alteration of the arrangement of salt bridges and of the network of water
      molecules/H-bonds that participates in the retinol-RBP interaction, an
      appreciable increase of the volume of the beta-barrel cavity, a considerably
      higher degree of mobility of the RBP-bound ligand and of several protein regions
      and the disorder of a large number of solvent molecules that are ordered at
      neutral pH. These changes are likely to be accompanied by a modification of the
      pattern of charge distribution on the protein surface. All these changes, which
      reveal a substantially lowered conformational stability of RBP, presumably occur
      at the initial stages of the acidic denaturation of RBP and are possibly
      associated with a facilitated release of the retinol molecule from its carrier
      protein.

PMID- 12787683
TI  - In vitro effect of chitin particles on the innate cellular immune system of
      gilthead seabream (Sparus aurata L.).
AB  - The interaction between chitin particles and gilthead seabream (Sparus aurata L.)
      head-kidney leucocytes, as well as their effects on the main innate cellular
      immune responses were studied. Three different chitin particle-sizes were tested:
      unfiltered, <10 microM and >10 microM. Leucocytes were able to phagocytose only
      the chitin particles of <10 microM but not the >10 microM ones. Leucocytes were
      incubated with different concentrations (0 to 1000 microg ml(-1)) of the above
      chitin particles for 1, 4, 24 or 48 h and their effects on leucocyte viability
      and the innate cellular immune system were evaluated. Leucocytes incubated with
      chitin for 48 h maintained their viability as determined by the MTT viability
      test. Leucocyte phagocytosis of bacteria after chitin incubation for 1 or 4 h was
      enhanced by the highest chitin concentration tested of each of the chitin
      fractions studied, while the respiratory burst activity was unaffected. As
      regards leucocyte natural cytotoxic activity against tumour cells, prior
      incubation of leucocytes with chitin particles for 1 or 4 h increased while
      incubation for 24 or 48 h reduced the cytotoxic activity in a dose dependent
      manner. Statistically significant differences between the different chitin
      concentrations and between the three chitin particle-size fractions were
      detected. To conclude, gilthead seabream head-kidney leucocytes were able to
      phagocytose chitin particles smaller than 10 microM, and the main cellular innate
      immune activities were enhanced as a consequence of prior incubation with chitin
      particles.

PMID- 12787684
TI  - The spotted wolffish (Anarhichas minor Olafsen) complement component C3:
      isolation, characterisation and tissue distribution.
AB  - The complement component C3 was isolated from spotted wolffish (Anarhichas minor
      Olafsen) serum by polyethylene glycol precipitation, anion exchange
      chromatography and gel filtration. Silver staining in SDS-PAGE and rabbit anti
      wolffish C3 antiserum used in Western blotting revealed that spotted wolffish C3
      contains two polypeptide chains, M(r)65 and 115kDa, respectively. The high
      molecular weight alpha-chain of the C3 incorporated 14C-methylamine suggesting
      that it contained a reactive thioester group. The deduced amino acid sequence,
      after screening a liver cDNA expression library, showed that the wolffish C3
      contained key amino acids for binding C3 convertase, factor H, I and properdin.
      Also, high degree of homology to other vertebrate C3 was found in the beta-alpha
      junction site. Phylogenetic tree analysis indicated that the Japanese flounder
      and spotted wolffish that belong to order pleuronectiformes and perciformes,
      respectively, are phylogenetically close species. Immunohistochemical experiments
      showed that liver hepatocytes and blood contained C3, and in situ hybridisation
      experiments revealed that liver hepatocytes expressed C3.

PMID- 12787685
TI  - Flow cytometric analysis of the neutrophil respiratory burst of ayu, Plecoglossus
      altivelis: comparison with other fresh water fish.
AB  - Neutrophils of vertebrates undergo respiratory burst activity (RBA) as a defense
      mechanism against bacterial infections. We report here that ayu (Plecoglossus
      altivelis) have unusually high RBAs even when they are in a healthy condition.
      Kidney and blood leukocytes were obtained from ayu, rainbow trout (Oncorhynchus
      mykiss), carp (Cyprinus carpio), eel (Anguilla japonica), and pond smelt
      (Hypomesus nipponensis). Neutrophil RBA was measured by flow cytometry using
      dihydrorhodamine after stimulation with phorbol myristate acetate. The amount of
      RBA of neutrophils from both blood and kidney was significantly higher in ayu
      than in the other species (e.g. the fluorescence intensity of ayu blood
      neutrophils was about 3-7 times higher than that from trout and carp, and that of
      ayu kidney neutrophils was 2-19 times higher than that of rainbow trout, carp,
      eel, and pond smelt). This unique character of ayu neutrophils was invariable
      even at different ages, locations, and sex-maturation stages.

PMID- 12787686
TI  - DNA vaccination against viral haemorrhagic septicaemia (VHS) in rainbow trout:
      size, dose, route of injection and duration of protection-early protection
      correlates with Mx expression.
AB  - Rainbow trout of different sizes (10 and 100g) were injected intramuscularly
      (i.m.) or intraperitoneally (i.p.) with different doses (range 10 ng-10 microg)
      of a viral haemorrhagic septicaemia (VHS)-DNA vaccine (pcDNA3vhsG). As controls,
      fish were injected with the pcDNA3 plasmid alone, or with inactivated VHS virus.
      Fish were challenged at different times post-vaccination (p.v.) to assess
      protection. At certain times p.v., serum samples were analysed for neutralising
      antibody and liver tissue was analysed for Mx mRNA expression. A DNA dose of 0.5
      microg injected by the i.m. route induced protection in fish of all sizes in
      challenges performed either 1 or 4 weeks p.v. This dose also conferred effective
      protection up to 9 months p.v. in fish >100 g. With lower doses of DNA (0.1 and
      0.01 microg) and challenge at 4 weeks p.v., 10 g fish were partially protected
      but protection was not observed in 100 g fish. Vaccination by the i.p. route
      induced no or lower levels of protection compared with the i.m. route. Fish
      vaccinated with 0.5 microg DNA i.m. had no detectable serum neutralising antibody
      (NAb) at 4 weeks p.v. (with the exception of a single 10 g fish) but antibody was
      detected at 8 weeks and 6 months p.v. but not at 9 months p.v. However, cohorts
      of these fish showed effective protection at all timepoints. Lack of detectable
      levels of NAb (at 9 weeks p.v.) despite partial protection in challenge at 4
      weeks p.v. was also observed with 0.01 microg doses of DNA i.m. NAb was detected
      in sera of fish at 8 weeks after vaccination with 0.1 microg i.m. but not in fish
      vaccinated with doses of 0.01-0.5 microg i.p. Early protection (1 week p.v.)
      correlated with elevated Mx gene expression.

PMID- 12787687
TI  - The kinetics of antibody production in mucus and serum of European eel (Anguilla
      anguilla L.) after vaccination against Vibrio vulnificus: development of a new
      method for antibody quantification in skin mucus.
AB  - Vibrio vulnificus serovar E, a bacterial pathogen for eels cultured in intensive
      systems, is transmitted through water and enters into new hosts mainly via gills.
      The main objective of this work was to study the kinetics of antibody production
      to V. vulnificus in serum and mucus and their relationship with protection after
      vaccination. To quantify local mucus antibodies, a new "in situ" dot blot
      immunoassay using image analysis has been developed. This assay was applied to
      measure antibody production in the skin zone next to the gills. We found that (i)
      the immune response in mucus was faster (peak at days 3-4) and shorter in
      duration (titres significantly elevated up to day 5 and 11 for skin zone next to
      the gills and for general cutaneous mucus, respectively) than in serum (peak at
      day 7; titres significantly elevated for more than 25 days); (ii) the exposure of
      vaccinated eels with basal levels of local antibodies to sub-lethal dose of the
      pathogen stimulated a more lasting secreted antibody production (for more than 14
      days); (iii) protection and antibody levels in serum were clearly correlated, and
      (iv) immunised eels with basal levels of serum antibodies and maximal levels of
      local antibodies were partially protected.

PMID- 12787688
TI  - Cloning and characterisation of a cDNA encoding Japanese flounder Paralichthys
      olivaceus IgD.
AB  - A cDNA containing the gene for Japanese flounder IgD consisted of 3240 bp
      encoding 998 amino acid residues. The amino acid sequence of the constant region
      of Japanese flounder IgD shares 38-80% identity with the sequences of previously
      reported teleost IgDs. The structure of the constant region of Japanese flounder
      IgD, which contains the micro1, delta1, delta2, delta3, delta4, delta5, delta6,
      delta7, and TM regions, is similar to the structures of the constant regions of
      the IgDs of channel catfish and Atlantic salmon. Southern blot hybridisation
      showed that the Japanese flounder IgD gene exists as a single locus. The Japanese
      flounder IgD gene was mainly detected in peripheral blood leucocytes (PBLs) and
      small amounts were detected in the spleen, head and trunk kidney, although IgM
      mRNA was detected in similar amounts in PBLs, the head kidney, and spleen. The
      copy number of IgM mRNA in Japanese flounder PBL was 56-fold higher than that of
      IgD.

PMID- 12787689
TI  - What is appropriate coronary assessment prior to abdominal aortic surgery?

PMID- 12787690
TI  - An appraisal of different cardiac risk reduction strategies in vascular surgery
      patients.
AB  - OBJECTIVES: to summarize existing evidence regarding the benefits and the risks
      of all available interventional and medical means aimed at cardiac risk reduction
      in patients undergoing vascular surgery. DESIGN: review of the literature.
      MATERIALS AND METHODS: a critical review of all studies examining the impact of
      various prophylactic cardiac maneuvers on perioperative outcome following
      vascular surgery was performed. Overall mortality, cardiac mortality and
      myocardial infarction rate were used as the outcome measures. RESULTS: coronary
      artery bypass grafting is associated with a 60% decrease in perioperative
      mortality in patients undergoing vascular surgery, but in most of the cases this
      decrease does not outweigh the combined risk of the cardiac and the subsequent
      noncardiac vascular procedure. Data supporting the cardioprotective effect of
      percutaneous transluminal angioplasty in the perioperative setting are
      insufficient. beta-blockade has been shown to decrease perioperative mortality
      and cardiac morbidity in both high-risk (strong evidence) and low-risk (weak
      evidence) patients. CONCLUSIONS: coronary revascularization is rarely indicated
      to simply get the patient through vascular surgery and should be reserved for
      patients who would need it irrespective of the scheduled vascular procedure.
      Among all available pharmacological agents, including beta-blockers, alpha
      agonists, calcium channel blockers and nitrates, only beta-blockers have been
      proven to reduce the cardiac risk of vascular surgery.

PMID- 12787691
TI  - Ethnicity and peripheral arterial disease.
AB  - INTRODUCTION: the prevalence of peripheral arterial disease (PAD) is relatively
      well defined for the Caucasian population. Given the susceptibility of Asians and
      Afro-Caribbeans to coronary heart disease and stroke respectively, and the high
      prevalence of cardiovascular risk factors in both groups, one would expect a high
      prevalence of peripheral arterial disease. METHODS: a search of MEDLINE (1966
      2002) was undertaken for studies on the incidence and prevalence of PAD,
      abdominal aortic aneurysms (AAA) and cerebrovascular disease in different ethnic
      groups. RESULTS: there are very few population-based prevalence studies assessing
      PAD, AAA or cerebrovascular disease in non-Caucasians. A review of hospital-based
      series demonstrates different patterns of PAD between ethnic groups. Blacks and
      Asians have a tendency towards more distal occlusive disease and AAA appear to be
      predominantly a disease of Caucasians. It is not clear whether these studies
      provide a true representation of the prevalence of arterial disease in various
      ethnic groups or are the result of an unmet health care need. CONCLUSIONS:
      further studies are required to establish the prevalence, natural history and
      response to treatment of PAD, AAA and cerebrovascular disease in non-Caucasians.
      Only when this has been achieved, can clinically and cost-effective health care
      be delivered to affected individuals from different ethnic groups.

PMID- 12787692
TI  - The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity
      ulcers: a double-blind randomised-controlled trial.
AB  - OBJECTIVE: ischaemic lower-extremity ulcers in the diabetic population are a
      source of major concern because of the associated high risk of limb-threatening
      complications. The aim of this study was to evaluate the role of hyperbaric
      oxygen in the management of these ulcers. METHOD: eighteen diabetic patients with
      ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind
      study. Patients were randomly assigned either to receive 100% oxygen (treatment
      group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min
      daily (total of 30 treatments). RESULTS: healing with complete epithelialisation
      was achieved in five out of eight ulcers in the treatment group compared to one
      out of eight ulcers in the control group. The median decrease of the wound areas
      in the treatment group was 100% and in the control group was 52% (p=0.027). Cost
      effectiveness analysis has shown that despite the extra cost involved in using
      hyperbaric oxygen, there was a potential saving in the total cost of treatment
      for each patient during the study. CONCLUSION: hyperbaric oxygen enhanced the
      healing of ischaemic, non-healing diabetic leg ulcers and may be used as a
      valuable adjunct to conventional therapy when reconstructive surgery is not
      possible.

PMID- 12787693
TI  - Prevalence and distribution of coronary disease in claudicants using 12-lead
      precordial stress electrocardiography.
AB  - AIMS: to evaluate the prevalence of coronary artery disease (CAD) by means of
      modified stress electrocardiography in patients presenting with intermittent
      claudication. METHODS: three hundred consecutive patients (188 male) with
      intermittent claudication (post-exercise ankle brachial index <0.8), and 100 age
      and sex-matched controls, were assessed for CAD with resting and stress 12-lead
      precordial ECG. A history of angina and previous myocardial infarction (MI) was
      recorded. EXCLUSION CRITERIA: recent (<1 month) MI; unstable angina; prior
      coronary intervention; arrhythmias; conduction abnormalities; uncontrolled
      hypertension; heart failure, digoxin therapy, and inability to perform tests.
      RESULTS: based on antecedent angina, MI and abnormal resting ECG, CAD prevalence
      was 47% in claudicants and 6% in controls; on 12-lead-precordial ECG stress
      testing, CAD prevalence was 46% (95% CI: 40.1-51.7%) in claudicants and 11% (95%
      CI: 4.8-17.2%) in controls (both p <0.0001). Only 67% of claudicants (n=141) with
      antecedent angina, MI or an abnormal resting ECG, met the criteria of CAD on
      stress testing; also 28% of claudicants without antecedent angina, MI and a
      normal resting ECG (n=159) had evidence of CAD. The odds ratio for CAD in
      claudicants was 6.9. Based on 12-lead-precordial ECG stress testing we detected
      the presence of: one-, two- and three-vessel disease in 14.7% (95% CI: 10.6
      18.7%), 19% (95% CI: 14.5-23.5%) and in 12.3% (95% CI: 8.6-16%) of claudicants;
      and in 8, 3 and 0% of controls, respectively. CONCLUSIONS: forty six percent of
      patients with intermittent claudication had concomitant CAD, and 31% two- or
      three-vessel disease. In the presence of claudication the odds ratio for CAD is
      6.9 (95% CI: 3.5-13.4) and for two- or three-vessel disease 14.8. Non-invasive
      modified stress electrocardiography by enabling identification of those with
      multi-vessel CAD and thus by providing cardiac risk stratification may help
      bridge the gap between clinical evaluation and invasive coronary imaging.

PMID- 12787694
TI  - Results of urgent and emergency thoracic procedures treated by endoluminal
      repair.
AB  - INTRODUCTION: emergency surgery on the thoracic aorta is associated with a high
      mortality. Endovascular treatment for these patients may offer a realistic
      alternative to open surgery. METHOD: between 1997 and 2002 data was collected
      prospectively on all patients who underwent urgent or emergency endoluminal
      repair for thoracic aortic pathology. All patients had ruptured or were at risk
      of rupture, and had been assessed as high risk for open surgery. RESULTS: twenty
      four patients required urgent/emergency stent grafts. The median age was 74
      (range 17-90). Indications included: trauma (transection in 3 and traumatic
      dissection in 1), acute symptomatic type B dissection (4), symptomatic
      degenerative aneurysms (7), false aneurysms associated with infection (6),
      Takayasu's vasculitis causing rupture of the descending thoracic aorta (1),
      symptomatic aneurysm associated with chronic dissection (1) and a secondary aorto
      oesophageal fistula (1). The 30-day survival was 83.3% (20/24) and the survival
      at 1 year was 70.8% (17/24). The median follow-up was 13.5 months (range 2-57).
      The complications included: transient paraplegia (1), non-disabling stroke (1),
      distal endoleak treated with an extension cuff (1) and a proximal endoleak (1)
      which required removal of the graft at open surgery. CONCLUSION: endoluminal
      repair of thoracic aortic disease requiring urgent/emergency treatment has
      encouraging results with low morbidity and mortality rates compared with open
      surgery. Long-term follow-up is required to assess the durability of the grafts.

PMID- 12787695
TI  - Endovascular treatment of thoracic aortic pathology: feasibility and mid-term
      results.
AB  - OBJECTIVE: to report our experience with 21 consecutive patients treated with a
      thoracic stent-graft. DESIGN: retrospective analysis. MATERIALS AND METHODS:
      Between October 1998 and February 2002, 21 patients (12 male), mean age 55.6
      years (range 19-86 years), were treated for aorticortic pathology localized to
      the descending aorta (18 patients), the aortic arch (2 patients) and the
      ascending aorta (1 patient) and comprising true aneurysms (8 patients), false
      aneurysms (6 patients), traumatic rupture (4 patients), mycotic aneurysms (2
      patients), and ruptured aneurysm (1 patient). Plain chest X-rays and computed
      tomography was performed at 3, 6 and 12 months postoperatively and then annually.
      RESULTS: the median (range) operation time was 85min (50-305min), hospital stay 6
      days (3-63 days) and follow-up 24 months (5-44 months). Complications occurred in
      5 patients and comprised intraoperative migration (1), type I endoleak (1), type
      II endoleak (1), ischemic myelopathy (1), pneumonia (2), suture granuloma (1) and
      common femoral artery dissection (1). CONCLUSIONS: stent-grafting can be
      successfully employed to treat a wide range of thoracic aortic pathologies with a
      mortality, morbidity and resource utilization that is considerably less than that
      associated with conventional surgery. However, long term follow-up on safety and
      efficacy is needed.

PMID- 12787696
TI  - Overexpression of transforming growth factor beta1 in smooth muscle cells of
      human abdominal aortic aneurysm.
AB  - OBJECTIVE: to examine the expression of transforming growth factor beta1 (TGF
      beta1) and the cell kinetics of smooth muscle cells (SMCs) at the neck of
      abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: expression of alpha
      smooth muscle actin and TGF-beta1 was evaluated by immunostaining, and cell
      kinetics were estimated by terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end-labeling (TUNEL) assay and Ki-67 immunostaining in 11 AAAs (at
      both the dilated region and the neck) and eight occlusive aortas. RESULTS: the
      TUNEL-positive SMC ratio in the neck and dilated region was significantly higher
      than in the occlusive aorta (p<0.01). The percentage of Ki-67-positive SMCs in
      the neck was significantly higher than in the dilated region (p<0.01) and the
      occlusive aorta (p=0.032). When compared with the occlusive aorta, the aneurysmal
      neck had increased TGF-beta1 expression (p=0.01) and reduced SMC density, and the
      aneurysmal dilated aorta had much more increased TGF-beta1 expression (p<0.01)
      and much more reduced SMC density (p<0.01). CONCLUSIONS: these results suggest
      that overexpression of TGF-beta1 might be associated with the reduction of SMC
      density through SMC apoptosis and reduced proliferative ability of SMCs, leading
      to dilatation in AAAs.

PMID- 12787698
TI  - Accessibility of calf perforating veins from the superficial posterior
      compartment: an anatomic dissection study.
AB  - OBJECTIVES: to determine the anatomic location of medial perforating veins (PVs)
      and their course within the compartments of the leg. MATERIALS AND METHODS: the
      lower extremity veins of 15 cadavers were filled with coloured latex solution.
      Medial PVs between the ankle and the knee were dissected out. RESULTS: in total
      95 direct PVs (mean 6.3 per extremity, range 3-9) were identified and classifed
      as Cockett I, II, or III, proximal and distal paratibial and Boyd. Cockett PVs
      were present in more than half of the cases, of which the majority (except
      Cockett I) were located in the superficial posterior compartment. Whereas the
      vast majority of Cockett PVs originate from the posterior arch vein, the other
      perforators originate from the greater saphenous vein. CONCLUSIONS: only 62% of
      all PVs pass through the superficial posterior compartment. As a result, during
      subfascial endoscopic perforating vein surgery (SEPS), at least one third of
      patients require a paratibial fasciotomy in order to reach and ligate the PVs.

PMID- 12787697
TI  - Relationships between activators and inhibitors of plasminogen, and the
      progression of small abdominal aortic aneurysms.
AB  - OBJECTIVE: plasmin is a common activator of the known proteolytic systems
      involved in the aneurysmal degradation, and is reported to be associated with the
      expansion of abdominal aortic aneurysms (AAA). The aim of this study was to study
      the activating pathways of plasminogen as predictors of the progression of AAA.
      MATERIALS AND METHODS: one hundred and twelve of 122 male patients with a small
      AAA (def.: +3cm) were interviewed, examined, had blood samples taken at
      diagnosis, and scanned annually for 1-5 years (mean 3.5 years), and referred for
      surgery if the AAA exceeded 5cm in diameter.A random sample of 70 of the 112
      cases had plasma levels of urokinase-like-plasminogen activator (uPA), tissue
      type-plasminogen activator (tPA), plasminogen-activator-inhibitor-1 (PAI-1),
      macrophage inhibiting factor (MIF), tumour-growth-factor-beta1 (TGF-beta1),
      homocysteine, and serum levels of IgA-antibodies against Chlamydia pneumoniae
      (IgA-CP) and Cotinine (a nicotine metabolite) measured. Spearmans correlation
      analysis was used for statistics. RESULTS: the annual expansion rate correlated
      positively with tPA, IgA-CP and S-Cotinine; r =0.37 (p=0.002), 0.29 (p=0.006) and
      0.24 (p=0.038), while PAI1, uPA, TGF-beta1, homocysteine, and MIF did not. S
      Cotinine did also correlate positively with tPA, r=0.24 (p=0.049). CONCLUSION:
      the aortic matrix degradation in AAA may be partly caused by an activation of
      plasminogen by tPA, but apparently not by uPA, which usually dominates matrix
      degradation. Smoking seems to be a factor for this pathway, while the pathways of
      IgA-CP and MIF, a new marker of aneurysmal progression, seem different. The
      latter observations suggest that other proteolytic pathways are involved in the
      aortic wall degradation in AAA.

PMID- 12787699
TI  - Venous disease is associated with an impaired range of ankle movement.
AB  - OBJECTIVES: to investigate the relationship between clinical severity of venous
      disease, calf muscle pump dysfunction and range of ankle movement (ROAM).
      MATERIALS AND METHODS: ROAM was assessed by goniometry in the supine,
      nonweightbearing position. Calf muscle pump function was assessed by ambulatory
      venous pressure (AVP), calculating the pressure relief index (PRI). Venous
      disease was classified according to the CEAP classification (International
      Consensus Committee reporting standards on venous disease). Forty seven limbs in
      38 adults were recruited and matched for age: 11 normal controls CEAP(0), 12
      varicose veins CEAP(2), 12 chronic venous insufficiency CEAP(4,5) and 12 active
      ulceration CEAP(6). RESULTS: mean (S.E.M.) age was 60.7 (1.3) years. Mean
      (S.E.M.) PRI was 1959.6 (313.7) in CEAP(0), 905.3 (139.3) in CEAP(2), 596.5
      (148.5) in CEAP(4,5) and 170.6 (69.0) in CEAP(6) (p < 0.001, ANOVA). Mean
      (S.E.M.) ROAM was 61.3 (2.0) degrees in CEAP(0), but significantly reduced to
      49.7 (2.0) in CEAP(2), 42.1 (2.6) in CEAP(4,5) and 40.9 (2.7) in CEAP(6) (p <
      0.004, ANOVA post hoc Tukey). PRI correlated with ROAM (p < 0.001, Pearson
      correlation coefficientr = 0.52). CONCLUSIONS: limbs with venous hypertension
      have a reduced range of ankle movement related to the clinical severity of venous
      disease.

PMID- 12787700
TI  - Does the pattern of venous insufficiency influence healing of venous leg ulcers
      after skin transplantation?
AB  - AIMS: this study aimed to investigate the influence of venous insufficiency on
      results in venous leg ulcers treated with ulcer excision, meshed split-skin
      transplantation and correction of superficial venous insufficiency in the wound
      area. DESIGN: retrospective cohort study. SETTING: Copenhagen Wound Healing
      Center. METHODS: in 113 patients with venous leg ulceration, examined
      preoperatively with colour Duplex scanning (CDS), prognostic factors of healing
      and recurrence within 1 year were analysed using logistic regression. RESULTS:
      cumulative 1-year healing rate was 65% (73 patients) and 13 (12%) had recurrence
      of ulceration 1 year postoperatively. Initial ulcer size (OR: 0.97(95% CI: 0.96
      0.99)), minor local superficial venous surgery (OR: 2.38 (95% CI: 1.04-5.46)),
      sufficient popliteal vein (2.97 (1.05-8.42)) and non-compliance with compression
      therapy (OR: 0.27 (95% CI: 0.11-0.71)) influenced the prognosis of healing
      positively. No statistically significant differences in healing and recurrence
      between patients with isolated superficial and mixed superficial/deep venous
      insufficiency was found. CONCLUSION: non-healing venous leg ulcers can be treated
      with ulcer excision, meshed split-skin transplantation and correction of
      superficial venous insufficiency in the wound area with beneficial results
      irrespective of underlying pattern of venous insufficiency as determined by CDS.

PMID- 12787701
TI  - Risk factor documentation in elective and emergency vascular surgical admissions.
AB  - OBJECTIVES: this study investigates current practice of risk factor documentation
      in a vascular unit and compares variations in risk factor assessment between
      elective and emergency admissions. METHODS: one hundred and forty-four patients
      who underwent vascular surgical intervention for atherosclerotic disease during
      the year 2000 were retrospectively identified from computerised database. Case
      note review collated demographic details, data on risk factor assessment and the
      nature of surgery. Data were analysed using SPSS statistical software. RESULTS:
      the male to female ratio was 2.3:1 with a median (range) age of 73 (31-95) years.
      For 55 (38%) emergency admissions the following risk factors were not documented;
      ischaemic heart disease (8), diabetes mellitus (10), hypertension (10), smoking
      habit (13) and antiplatelet therapy (18). For 89 (62%) elective admissions the
      following risk factors were not documented; ischaemic heart disease (11),
      diabetes mellitus (9), hypertension (4), smoking habit (5) and antiplatelet
      therapy (19). Sixty-six (72.5%) routine admissions and 11 (20.8%) emergency
      admissions had estimations of serum cholesterol documented (chi(2) p < 0.001).
      There were no statistically significant differences in the documentation of other
      risk factors between the 2 groups. CONCLUSION: risk factors are not documented
      consistently for emergency vascular surgical admissions. Staff education should
      aim to improve risk factor assessment for elective and emergency admissions to
      reduce cardiovascular events and possibly improve surgical outcome in patients
      with atherosclerotic disease.

PMID- 12787702
TI  - An audit of out of hours interventional vascular radiology.
AB  - BACKGROUND: in 1996 the Royal College of Radiologists established a set of
      guidelines for out of hours radiology. Part of the recommendations determined
      that all units should regularly assess their own out of hours workload. In light
      of these guidelines we have audited our units interventional radiology activity.
      METHODS: this was a retrospective study looking at the number of emergency
      angiograms and procedures performed over a 1-year period. Patients were
      identified from a vascular radiology database and case notes reviewed. RESULTS: a
      total of 1902 patients had angiograms with 686 having further procedures. Of
      these, 1093 patients (57%) having 380 procedures (55%) were under the care of a
      consultant vascular surgeon. Of the vascular surgical patients only 17 patients
      (1.6%) were actually investigated out of hours (1700-0800 weekdays and at
      weekends). 5/17 (29%) patients received thrombolysis and 7/17 (41%) had either an
      angioplasty or stent. Despite being a major vascular unit only 2/17 (12%) were
      patients referred from outside the units own trust. Following diagnostic
      angiography, 13/17 (76%) of patients had an intervention performed within the
      first 24h. CONCLUSION: in a unit performing a large number of angiograms only a
      small number of patients require out of hours emergency angiography and
      interventional vascular procedures. Our impression is that this is the result of
      a flexible and responsive in hour's service. At the present time extra-hospital
      referrals do not appear to generate large amounts of out of hours work. This
      level of out of hours activity has implications in the provision of vascular
      radiological services in the future.

PMID- 12787703
TI  - Subintimal angioplasty as a treatment of femoropopliteal artery occlusions.
AB  - OBJECTIVES: to report the results of subintimal PTA of femoropopliteal occlusions
      above the knee. DESIGN: a retrospective study. PATIENTS: in the period from
      January 1997 to January 2002, 109 patients were submitted to 124 interventions.
      The indication for treatment was intermittent claudication in 78 cases and
      critical ischaemia in 46. METHODS: all cases of subintimal angioplasty were
      prospectively registered. A review of all cases treated with subintimal PTA for
      above-knee femoropopliteal occlusions were done. Primary assisted haemodynamic
      patency rate was calculated on intention to treat basis and for successfully
      treated cases. Comparison of patency with respect to comorbidities, indication,
      runoff and occlusion length was done with univariate and multivariate analysis
      (Cox' regression). RESULTS: technical success rate was 90%. Primary assisted
      patency rates at 6, 12 and 18 months were 43, 37 and 31% calculated on basis of
      intention to treat and 48, 42 and 35% for successfully treated cases. Diabetes
      mellitus and critical ischaemia were found to be independent risk factors for re
      occlusion. CONCLUSION: subintimal angioplasty is an alternative to open surgery
      for patients with femoropopliteal occlusions and intermittent claudication. The
      treatment is relatively atraumatic, complications are rare and in most cases
      treated with endovascular techniques. Patency rates are low. In cases of critical
      ischaemia, time can be important for outcome with respect to limb salvage. We
      therefore find that the poor patency rates of subintimal angioplasty of
      femoropopliteal occlusions contraindicate its use in the treatment of critical
      ischaemia with exception of cases unsuitable for surgical treatment.

PMID- 12787704
TI  - Remote endarterectomy: first choice in surgical treatment of long segmental SFA
      occlusive disease?
AB  - OBJECTIVES: to report the long term results of remote superficial femoral artery
      endarterectomy (RSFAE) with the MollRing Cutter for the treatment of long
      segmental SFA occlusive disease. DESIGN: retrospective open study. PATIENTS AND
      METHODS: from March 1994 to August 2000 183 RSFAEs were performed in 164 selected
      patients (105 males, 120 procedures) with a median age of 63 years (43-84 years).
      Indications for operation were disabling intermittent claudication in 129
      procedures (70%), rest pain in 20 procedures (11%), and limb salvage in 34
      procedures (19%). Follow up consisted of clinical evaluation, ankle-brachial
      index measurements and duplex scanning. RESULTS: the mean follow-up time was 29.3
      months. The mean length of the endarterectomised SFAs was 31 cm (range, 17-45cm).
      The five year cumulative primary patency rate by means of life table analysis was
      37.8+/-6.67% (SE). Percutaneous transluminal balloon angioplasty and surgical re
      intervention were performed in twenty-nine and four patients respectively
      resulting in a primary assisted patency rate of 47.9+/-6.27%. Limb salvage was
      achieved in 30 of the 34 patients. Females had a statistically significant lower
      primary patency rate, i.e., 26 vs 45% (p -value=0.01). CONCLUSIONS: the long term
      results of remote SFA endarterectomy show that it is a safe, effective and
      durable, minimally invasive procedure. It also leaves open all other options for
      conventional bypass procedures. The five-year primary patency rate is at least
      similar to prosthetic above-knee bypass surgery.

PMID- 12787705
TI  - A ruptured aneurysm of superior mesenteric artery to duodenum and reconstruction
      with saphenous vein graft.

PMID- 12787706
TI  - Venous thoracic outlet syndrome secondary to congenital pseudoarthrosis of the
      clavicle. Presentation in the fourth decade of life.

PMID- 12787710
TI  - Early diagnosis and surgical management of prostate cancer.
AB  - Prostate cancer is a significant cause of morbidity and mortality in the United
      States and Europe. The natural ageing of the population as well as the continued
      and widespread use of diagnostic tests such as prostate specific antigen (PSA),
      has led to an increase in the numbers of men diagnosed with localised prostate
      cancer. Screening to identify organ-confined disease has provoked much public and
      scientific attention, but remains controversial. Radical prostatectomy is one of
      the most challenging urological procedures performed. Improvements in technique
      due to better understanding of pelvic anatomy have reduced complications, with
      acceptable standards and excellent results in high-volume institutions. Continual
      refinements in technique and the recent introduction of laparoscopic radical
      prostatectomy are likely to improve functional outcome further. However the
      effectiveness of surgery in improving survival and quality of life, in men with
      early prostate cancer remains to be determined. The results from large randomised
      controlled trials are eagerly awaited.

PMID- 12787711
TI  - Radical radiotherapy for prostate cancer.
AB  - External beam radiotherapy is one of the curative treatment options for localised
      prostate cancer. This article will describe recent advances in prostate
      radiotherapy, focussing on the results of randomised trials which have addressed
      the role of radiation dose escalation and of adjuvant hormone therapy. Current
      controversies will then be considered, including the merits of radiotherapy in
      comparison with alternative approaches to early prostate cancer, and the possible
      role of adjuvant radiation following surgery. Finally, future developments will
      be described, including hypofractionation and dose individualisation, which have
      the potential to further improve the outcome of external beam radiotherapy for
      prostate cancer.

PMID- 12787712
TI  - Current strategies in the management of hormone refractory prostate cancer.
AB  - Prostate cancer is the most common cancer diagnosed in American males, and is the
      second leading cause of cancer-related deaths. Most patients who develop
      metastatic disease will initially respond to androgen deprivation, but response
      is invariably temporary. Most patients will develop androgen-independent
      ("hormone-refractory") disease that results in progressive clinical deterioration
      and ultimately death. This progression to androgen independence is accompanied by
      increasingly evident DNA instability and alterations in genes and gene
      expression, including mutations in p53, over-expression of Bcl2, and mutations in
      the androgen receptor gene, among others. Treatment options for hormone
      refractory disease include intensive supportive care, radiotherapy,
      bisphosphonates, second-line hormonal manipulations, cytotoxic chemotherapy and
      investigational agents. A post-treatment reduction in the level of prostate
      specific antigen (PSA) by 50% has been shown to correlate with survival and has
      been accepted by consensus as a valid endpoint in clinical trials.
      Chemotherapeutic agents such as mitoxantrone, estramustine, and the taxanes have
      yielded improved response rates and palliative benefit, but not improved
      survival. Therefore, current efforts must be focused on enrolling patients onto
      clinical trials of investigational agents with novel mechanisms of action, and on
      using survival, time to progression, and quality of life as end points in routine
      clinical practice.

PMID- 12787713
TI  - Pathophysiology of bone metastases from prostate cancer and the role of
      bisphosphonates in treatment.
AB  - Metastasis to bone is a common feature in advanced prostate cancer patients.
      Current treatments, while effective in suppressing tumour growth and relieving
      tumour associated bone pain, do not provide long term remission or 'cure' for the
      disease. A greater understanding of prostate cancer metastasis is required if new
      treatment strategies are to be developed. Growth of tumour foci in skeletal sites
      is a major cause of morbidity in advanced prostate cancer and has required the
      development of specialised approaches to treatment, including the use of
      bisphosphonates. These drugs inhibit tumour induced osteoclastic bone resorption,
      thereby preventing skeletal related events and treatment induced bone loss.
      Zoledronic acid is currently the only bisphosphonate with proven benefit in
      prostate cancer. Bisphosphonates may also modify the bone microenvironment so
      that it becomes less favourable for the growth and survival of metastases. The
      most recent developments in our understanding of the advantages for growth and
      survival gained by metastatic prostate cancer cells in the skeleton are reviewed,
      along with the clinical evidence supporting the use of bisphosphonates in
      advanced prostate cancer.

PMID- 12787714
TI  - Immunotherapy and prostate cancer.
AB  - Prostate cancer is the second leading cause of cancer death in the US, largely
      because of the limitations of our current therapeutic options, especially once
      the cancer has metastasized. Investigators have long sought new therapeutic
      modalities such as angiogenesis inhibitors, vaccines, and gene therapy, among
      others. It appears that a combination approach will be required to cure the
      majority of malignancies. Immunotherapy for prostate cancer appears feasible and
      a likely therapeutic modality in the armamentarium. Unfortunately, further
      research in basic immunology and the interaction of the immune system with other
      forms of therapy is needed. Many obstacles exist in immunotherapy, including
      vector design, tumouricidal specificity, and tumor evasion, which will have to be
      overcome in order to realize the maximum therapeutic benefit from this treatment
      modality.

PMID- 12787715
TI  - Management of treatment-related osteoporosis in men with prostate cancer.
AB  - Osteoporosis is an important and preventable adverse effect of androgen
      deprivation therapy for prostate cancer. Androgen deprivation therapy by either
      bilateral orchiectomies or administration of a gonadotropin-releasing hormone
      agonist decreases bone mineral density and increases fracture risk. Treatment
      related osteoporosis can be prevented by intermittent administration of either
      intravenous pamidronate or zoledronic acid. Pamidronate (60 mg intravenously
      every 3 months) prevents bone loss during androgen deprivation therapy.
      Zoledronic acid (4 mg intravenously every 3 months) not only prevents bone loss
      but also increases bone mineral density. Alendronate and other oral
      bisphosphonates may be effective but have not been evaluated in men with castrate
      testosterone levels. Oestrogen replacement therapy and treatment with selective
      ooestrogen receptor modulators may prevent bone loss during androgen deprivation
      therapy. Bicalutamide (150 mg daily) monotherapy increases serum ooestrogen
      levels and maintains bone mineral density.

PMID- 12787716
TI  - Conformal radiotherapy with dose escalation appears safe and effective in
      localised prostate cancer.

PMID- 12787717
TI  - Combined androgen blockade may have long term survival benefits over monotherapy,
      but may increase adverse effects and reduce quality of life in advanced prostate
      cancer.

PMID- 12787718
TI  - Early androgen suppression may reduce disease progression and improve long term
      survival compared with deferred androgen suppression in locally advanced prostate
      cancer.

PMID- 12787719
TI  - Adding androgen suppression to radiotherapy may improve disease-free survival
      over radiotherapy alone in locally advanced prostate cancer.

PMID- 12787720
TI  - Radical prostatectomy may improve disease-specific mortality, but not overall
      survival compared with watchful waiting in early prostate cancer.

PMID- 12787721
TI  - Watchful waiting and radical prostatectomy have similar quality of life in
      localised prostate cancer.

PMID- 12787722
TI  - Regulatory CD8+ T cells control thyrotropin receptor-specific CD4+ clones in
      healthy subjects.
AB  - One of the mechanisms ensuring immunological unresponsiveness or tolerance
      depends on the action of CD8(+) lymphocytes. In this paper, we report that, in
      healthy subjects, a subset of CD8(+)CD28(-) T cells suppresses the specific
      response to TSH receptor (TSHR) of CD4(+) clones. Suppression was highly
      specific, required cell-cell interaction, and was not mediated by cytotoxicity.
      Co-incubation of CD8(+) and CD4(+) clones, followed by the removal of the CD8(+)
      cells from the cultures before testing CD4(+) responsiveness to TSHR,
      demonstrated that CD4(+) cells were anergic since they showed low response to the
      antigen and a significant impairment of IL-2 production. In CD8-mediated anergy
      induction, the T-cell receptor (TCR) on both CD4(+) and CD8(+) cells seems to
      play a role. Our results indicate that one of the mechanisms ensuring peripheral
      tolerance involve CD8(+)CD28(-) cells. A disregulation in the control of
      autoreactive clones by this subset might be important for the onset of autoimmune
      thyroid diseases.

PMID- 12787723
TI  - Scaffold attachment region located in a locus targeted by hepadnavirus
      integration in hepatocellular carcinomas.
AB  - The role of viral integration in HBV induced hepatocellular carcinoma (HCC) is
      still controversial. In the WHV/woodchuck animal model, WHV integration was found
      to activate the N-myc2 oncogene either by enhancer insertion in proximity of the
      gene, or by integration in a distantly located uncoding locus, win. In addition,
      we have reported that N-myc2 activation also results from WHV integration in the
      b3n locus, located several kilobases downstream of N-myc2. In this work we report
      the search for function(s) of the b3n locus that might be possibly affected by
      WHV integration and indirectly activate N-myc2. A 0.5 kb region of the sequence
      of this locus exhibited unusual features, typical of scaffold/matrix attachment
      regions (S/MAR). Standard in vitro binding assays are commonly used to assess if
      a DNA fragment is a S/MAR. DNA fragments cloned from the b3n locus were tested
      for in vitro binding affinity for both heterologous and autologous nuclear
      scaffold preparations. Only the fragment spanning the region rich of S/MAR motifs
      was found to bind specifically nuclear scaffolds, thus demonstrating that a S/MAR
      element is present in the b3n locus. Based on these findings, we speculate that
      WHV integration might deregulate the S/MAR element and indirectly affect the
      expression of the N-myc2 gene located upstream of the S/MAR. Our findings also
      suggest that the role of HBV integration should be reconsidered, because a
      similar mechanism has not been investigated to date in human HCC.

PMID- 12787724
TI  - Serum p53 antibodies in correlation to other biological parameters of breast
      cancer.
AB  - Breast cancer is the second most frequent cancer of Thai women. Mutation of p53
      is a common event in breast cancer. This alteration can result in cellular
      accumulation of p53 and may also found in serum p53 antibodies (p53-Abs). To
      clarify prognostic significance of these antibodies, we evaluated p53-Abs in 158
      sera of patients with breast cancer. Thirty (19%) patients were found to have p53
      Abs. The incidence of p53-Abs tended to be higher in patients with advanced
      disease group (stages III and IV) than patients with early disease group (stages
      I and II) (P=0.055). Strong correlations were found between the presence of p53
      Abs and p53 protein expression (P<0.001) and lymph node status (P=0.021). The
      presence of p53-Abs was associated with lack of estrogen (ER) receptor expression
      (P=0.035) but was not related to progesterone receptor (PR) (P=0.567). In
      addition, there was a statistically significant correlation between p53-Abs and
      proliferation associated antigen Ki-67 (P=0.006), but no relation between c-erbB2
      oncoprotein and p53-Abs was observed (P=0.112). Additionally, no correlation was
      noted between the presence of p53-Abs and serum carcinoembryonic antigen (CEA) or
      carbohydrate antigen (CA15-3). Our findings indicate that p53-Abs appears to be a
      promising new parameter to evaluate the cellular biology and prognosis of breast
      cancer.

PMID- 12787725
TI  - Occupational physical activity and the risk of breast cancer.
AB  - The association between occupational and the risk of breast cancer was analyzed
      using data from a case-control study of 257 women with breast cancer and 565
      control women. Logistic regression was used to estimate odds ratios (ORs) and 95%
      confidence intervals (CIs) for occupations having light and medium activity
      compared with sedentary ones. After adjusted for potential confounders, women in
      sedentary occupations had a 29% higher risk, compared to those with the
      physically medium demanding jobs. For women at age > or =55 years higher
      occupational physical levels were associated with 53-60% reduction in the risk.
      There was a significant decreasing trend in the ORs from sedentary to medium work
      (P=0.001); while no association emerged in younger women. These findings
      demonstrate that the protective effect of higher levels activity in occupations
      on breast cancer appears to be confined to older women.

PMID- 12787727
TI  - Cervical cancer mortality among foreign-born women living in the United States,
      1985 to 1996.
AB  - PURPOSE OF STUDY: This study explored the potential influence of increasing
      immigration to the United States (US) on US cervical cancer mortality trends.
      BASIC PROCEDURES: Mortality data were derived from the National Center for Health
      Statistics' Detailed Mortality File. Population estimates were obtained from the
      US Bureau of the Census. Age-adjusted cervical cancer mortality rates were
      calculated for women living in the US according to place of birth. MAIN FINDINGS:
      From 1985 to 1996, deaths and death rates from cervical cancer increased for
      foreign-born women and decreased for US-born women. Increases in death rates
      among foreign-born women were highest in the South. Cervical cancer deaths and
      death rates for US-born women decreased uniformly in all regions. PRINCIPLE
      CONCLUSIONS: Cervical cancer mortality rates have increased among foreign-born
      women in the United States, and have influenced overall US cervical cancer
      mortality trends. Cervical cancer control efforts should be intensified in areas
      of the United States with large foreign-born communities.

PMID- 12787726
TI  - Enhancing the efficacy of chemotherapeutic drugs by the suppression of
      antiapoptotic cellular defense.
AB  - The study was aimed at evaluating the combination of a traditional anticancer
      drug doxorubicin (DOX) with a suppressor of antiapoptotic cellular defense-
      synthetic peptide corresponding to the minimal sequence of BCL-2 homology 3 (BH3)
      domain. BH3 peptide was delivered into cells by fusion with a peptide
      corresponding to the Antennapedia (Ant) internalization sequence. The
      cytotoxicity of DOX, Ant-BH3 and Ant-BH3 mixed in with DOX, mitochondrial
      transmembrane potential, expression of genes encoding pro- and antiapoptotic
      members of BCL-2 protein family and caspases, caspases activity, apoptosis
      induction were assessed in human ovarian carcinoma cells. It was found that the
      combination in one drug formulation of DOX and Ant-BH3 produced two main effects:
      (1) enhancing the apoptosis induction by an anticancer drug, and (2) preventing
      the development of antiapoptotic cellular drug resistance. The results confirmed
      that anticancer drug-BH3 combination might form the basis for a new advanced
      anticancer proapoptotic drug delivery systems.

PMID- 12787728
TI  - DNA adducts detected in human gastric mucosa.
AB  - Human gastrointestinal neoplasms are mostly developed from the mucosa, not from
      the adjacent muscle layer. DNA adducts in the mucosa and adjacent muscle layer of
      the non-tumoral part of stomach from 19 patients with gastric neoplasms and from
      six newborns were analyzed by 32P-postlabeling, and then compared them with those
      of representative colon or small intestine sample. Five kinds of mucosa-specific
      DNA adducts (G1-5) were found in all of the adult stomach samples, but were
      entirely absent from the adjacent muscle layers and from the newborn stomachs. In
      addition, several common background adducts were also present in both the mucosa
      and muscle layer. G2 was the same DNA adduct as Si2 in the small intestine and C1
      in the colon, and G3 was the same as Si1 in the small intestine. Thus, it was
      demonstrated that the mucosa of the stomach was exposed to DNA-reactive
      substances.

PMID- 12787729
TI  - Codon 201 polymorphism of DCC gene is a prognostic factor in patients with
      colorectal cancer.
AB  - The polymorphism at codon 201 of the "deleted in colorectal carcinoma" (DCC) gene
      has been liked to susceptibility to colorectal cancer. However, its
      clinicopathological significance has not been reported. We examined the codon 201
      polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length
      polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional
      mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did
      not significantly differ from normal to transitional mucosa and to tumor, but LOH
      was increased from transitional mucosa to tumor. Almost all of the LOH cases
      showed the polymorphism. The polymorphism was increased from well/moderately to
      poorly differentiated and to mucinous carcinoma (P=0.03). The polymorphism was
      more frequently seen in advanced stages than in earlier stages (P=0.02), and
      further predicted worse survival (P=0.04). The data suggest that the codon 201
      polymorphism of the DCC gene was a target of LOH, and predicted prognosis in
      colorectal cancer patients.

PMID- 12787731
TI  - Anti-angiogenesis and angioprevention: mechanisms, problems and perspectives.
AB  - The recognition that angiogenesis is a key early event in tumor progression and
      metastasis has led to the development of new strategies for cancer therapy. The
      generation of a new blood vessel network under physiological conditions is
      regulated by the concerted action of activators and inhibitors. Perturbation of
      this balance, as it occurs in solid tumor growth and metastasis, appears to be a
      critical point in tumorigenesis. This has led to the "angiogenic switch"
      hypothesis: the point at which a tumor acquires the potential to induce
      angiogenesis is a critical step towards malignancy. Based on experimental
      evidence, prevention of blood vessel development appears to be the mechanism of
      action of many successful chemopreventive drugs of natural or synthetic origin: a
      novel concept that we termed "angioprevention". The hypothesis that anti
      angiogenesis is at the basis of tumor prevention also suggests that many anti
      angiogenic drugs could be used for chemoprevention in higher risk populations or
      in early intervention. There is a growing body of experimental evidence that anti
      angiogenic strategies will contribute to the future therapy of cancer, several
      compounds with anti-angiogenic properties are now under clinical investigation
      including anti-inflammatory compounds, as inflammation may play a key role in
      angiogenesis. We must persevere in the development of novel, powerful and safer
      angiogenesis inhibitors and in the use of anti-angiogenic drugs in combination
      with other natural or synthetic anti-cancer agents in a biological therapy
      strategy.

PMID- 12787730
TI  - Comparative analysis of G2 arrest after irradiation with 75 keV carbon-ion beams
      and 137Cs gamma-rays in a human lymphoblastoid cell line.
AB  - Heavy-ion beams are more effective than gamma-rays in causing G2 arrest. In this
      study, we investigated the expression of Wee1 and Cdc2 protein levels in order to
      analyze the G2 arrest caused by carbon-ion beam irradiation. Human lymphoblastoid
      TK6 cells were exposed to a 75 keV carbon-ion beam or 137Cs gamma-rays. Although
      the levels of Wee1 and Cdc2 protein were increased after exposure to either beam,
      Wee1 protein levels were influenced more by carbon-ion beam irradiation than by
      gamma-rays. To the contrary, Cdc2 protein levels were increased more by gamma
      rays than by carbon-ion beams. These findings suggest that the G2 arrest produced
      by heavy-ion beams, such as the carbon-ion irradiation used in this study, might
      be associated with the overexpression of the Wee1 protein and of Cdc2
      phosphorylation regulated by Wee1. Together, these events may act to prolong the
      length of G2 arrest.

PMID- 12787732
TI  - SseA is required for translocation of Salmonella pathogenicity island-2 effectors
      into host cells.
AB  - The Salmonella pathogenicity island-2 (SPI2) is a virulence locus on the
      bacterial chromosome required for intracellular proliferation and systemic
      infection in mice. Cell culture models and a murine model of systemic infection
      were used to address the role of an uncharacterized SPI2 open reading frame,
      designated as sseA, in Salmonella virulence. A Salmonella strain with an unmarked
      internal deletion of sseA displayed a phenotype that was similar to an SPI2
      encoded type III secretion system apparatus mutant. Moreover, SseA was required
      for survival and replication within epithelial cells and macrophages. Murine
      infection studies confirmed that the DeltasseA strain was severely attenuated for
      virulence. Using immunofluorescence microscopy, the virulence defect in the
      DeltasseA strain was attributed to an inability to translocate SPI2 effector
      proteins into host cells. These data demonstrate that SseA is essential for SPI2
      mediated translocation of effector proteins.

PMID- 12787733
TI  - Influence of DNA encoding cytokines on systemic and mucosal immunity following
      genetic vaccination against herpes simplex virus.
AB  - The aim of our investigation was to improve the effectiveness of DNA vaccines
      against herpes simplex virus (HSV) infection. We chose coimmunization with DNA
      encoding cytokines known to emphasize components of immune defense that best
      correlate with immune protection. These include interferon-producing T and NK
      cells and the IgG2a isotype immunoglobulin. Our results show that the
      coadministration of plasmid DNA encoding IL-12 or IL-18 along with glycoprotein B
      (gB) DNA improves immune induction. Recipients of the coimmunization procedure
      had elevated humoral as well as IFN-gamma-producing T cell responses and showed
      greater resistance to vaginal challenge with a lethal dose of HSV-1. The adjuvant
      effects were observed when the vaccines were administered either systemically or
      mucosally. By most assays, the adjuvant effect of IL-18 was superior to IL-12,
      although gB DNA plus IL-18 failed to induce levels of immunity achieved by UV
      inactivated HSV immunization. Mucosal immunization proved as an effective means
      of inducing systemic immunity, but was less effective than the systemic route for
      inducing protection from vaginal challenge. Our results also demonstrated that
      protection from such challenges was mainly a property of IFN-gamma. Thus,
      immunized IFN-gamma-/- mice remained susceptible to challenges even while
      generating readily measurable immune responses. The approach of using DNA
      vaccines combined with DNA encoding cytokines holds promise and represents a
      potentially useful approach for vaccines.

PMID- 12787734
TI  - Prevalence and molecular diversity of pHS-2 plasmids, marker for
      arthritogenicity, among clinical Escherichia coli Shigella isolates.
AB  - Reactive arthritis can occur after numerous bacterial infections, including
      bacillary dysentery caused by Escherichia coli Shigella. A major risk factor for
      the disease is the HLA B27 phenotype in the human host. By comparison between
      plasmid profiles of arthritogenic vs. nonarthritogenic Shigella strains, the pHS
      2 plasmid has been previously associated with the arthritogenic capacity of
      Shigella isolates. However, the prevalence of this plasmid in the various
      Shigella biotypes and serotypes is largely unknown. On this background, 188
      clinical isolates from intestinal disease representing all 46 Shigella serogroups
      were studied for the presence of the pHS-2 plasmid, using PCR, dot blot and
      Southern blot techniques and by analysis of restriction fragment length
      polymorphisms. The pHS-2 plasmid was found in nine of 14 E. coli Flexneri
      serogroups, in E. coli Dysenteriae 1 and in E. coli Boydii 16. In addition, we
      show marked variability of this plasmid in E. coli Flexneri 3A and 4A strains.
      Major biological diversity of the pHS-2 plasmid was found to be strictly related
      to Shigella serogroups. The prevalence pattern of the pHS-2 plasmid matches
      published data on arthritogenic Shigella isolates, providing additional indirect
      evidence for the potential validity of this plasmid as a marker for
      arthritogenicity.

PMID- 12787735
TI  - Classification of Brucella strains isolated from marine mammals by infrequent
      restriction site-PCR and development of specific PCR identification tests.
AB  - Brucella strains have been isolated since the 1990s from a wide variety of marine
      mammals and represent potential zoonotic pathogens. They have distinctive
      phenotypic and molecular characteristics from the terrestrial mammal Brucella
      species, and two new species names have been previously proposed based on DNA
      polymorphism at the omp2 locus and their preferential host, i.e. Brucella
      cetaceae for cetacean isolates and Brucella pinnipediae for pinniped isolates.
      The results presented in this study on characterization of these strains by
      infrequent restriction site-PCR (IRS-PCR), taking into account the higher number
      of IS711 elements in their genome compared to terrestrial mammal Brucella
      species, supports this classification. The nucleotide sequences of specific DNA
      fragments detected by IRS-PCR were determined and used to develop PCR
      identification tests for either B. cetaceae or B. pinnipediae.

PMID- 12787736
TI  - Geographic dynamics of viral encephalitis in Thailand.
AB  - Viral encephalitis (VE) continues to be a major disease in Asia, causing serious
      illness which may result in death or have neurological sequelae. This study
      involves an ecological analysis of the climatic, geographic and seasonal patterns
      of clinically reported VE in Thailand from 1993 to 1998 to investigate regional
      and seasonal differences in disease incidence. Three thousand eight hundred and
      twenty nine cases of VE were clinically diagnosed nationwide during the study
      period by the Thai Ministry of Public Health. Spearman rank correlations of
      temporal, spatial and geographic variables with disease incidence were performed.
      The monthly incidence of VE correlated significantly with seasonal changes in
      temperature, relative humidity and rainfall in the north-northeast region of
      Thailand (P < 0.001), whereas incidence in the south-central region correlated
      only with relative humidity (P = 0.003). Spatial analysis revealed a positive
      correlation of disease with elevation (P < 0.001), and negative correlations with
      rice-field cover (P < 0.001), agricultural land-use (P < 0.001) and temperature
      (P = 0.004) in the north-northeast region. No significant spatial correlation was
      identified in the south-central region. The spatial distribution of VE suggests
      that etiologic variations may be responsible, in part, for the geographic
      patterns of disease. Active etiologic surveillance is necessary in a variety of
      geographic settings in order to provide physicians with information necessary for
      disease prevention and clinical management.

PMID- 12787737
TI  - Bacterial invasion by a paracellular route: divide and conquer.
AB  - The epithelium of the host plays an important first line of defense against most
      human pathogens. Microbial factors have been identified that are involved in the
      destruction of the structures that maintain the integrity of the epithelium. The
      mechanisms used by several, selected bacteria for the disruption of epithelial
      cell-cell junctions are discussed.

PMID- 12787738
TI  - Inducible nitric oxide synthase and control of intracellular bacterial pathogens.
AB  - Inducible nitric oxide synthase (iNOS) has important functions in innate immunity
      and regulation of immune functions. Here, the role of iNOS in the pathogenesis of
      various intracellular bacterial infections is discussed. These pathogens have
      also evolved a broad array of strategies to repair damage by reactive nitrogen
      intermediates, and to suppress or inhibit functions of iNOS.

PMID- 12787739
TI  - Mycobacterium tuberculosis gene expression in macrophages.
AB  - This review provides a discussion on the current information about the response
      of Mycobacterium tuberculosis to the environment encountered in the macrophage.
      We focus on the types of genes shown to be upregulated when the pathogen grows in
      macrophages and discuss the possible roles of these genes in adaptation to the
      conditions in the eukaryotic cell, in the context of enhancing the survival of
      the pathogen during infection.

PMID- 12787740
TI  - Molecular mechanisms of filovirus cellular trafficking.
AB  - The filoviruses, Ebola and Marburg, are two of the most pathogenic viruses,
      causing lethal hemorrhagic fever in humans. Recent discoveries suggest that
      filoviruses, along with other phylogenetically or functionally related viruses,
      utilize a complex mechanism of replication exploiting multiple cellular
      components including lipid rafts, endocytic compartments, and vacuolar protein
      sorting machinery. In this review, we summarize these recent findings and discuss
      the implications for vaccine and therapeutics development.

PMID- 12787741
TI  - Acinetobacter lwoffii infection and gastritis.
AB  - About 25% of humans with chronic gastritis are negative for Helicobacter pylori,
      suggesting that other bacteria are capable of causing inflammation. Bacterial
      overgrowth may occur in the stomach under conditions of reduced acid secretion.
      In this review, we will explore what is generally known about non-H. pylori
      organisms and their ability to induce gastritis, with particular focus on
      Acinetobacter lwoffi.

PMID- 12787742
TI  - Adaptation of Borrelia burgdorferi in the vector and vertebrate host.
AB  - Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, which
      afflicts both humans and some domestic animals. B. burgdorferi, a highly evolved
      extracellular pathogen, uses several strategies to survive in a complex enzootic
      cycle involving a diverse range of hosts. This review focuses on the unique
      adaptive features of B. burgdorferi, which are central to establishing a
      successful spirochetal infection within arthropod and vertebrate hosts. We also
      discuss the regulatory mechanisms linked with the development of molecular
      adaptation of spirochetes within different host environments.

PMID- 12787743
TI  - The origin and maintenance of virulence for the human pathogenic fungus
      Cryptococcus neoformans.
AB  - The origin of virulence in environmental fungi that have no requirement for
      animal hosts in their life cycle is enigmatic. Cryptococcus neoformans is a human
      pathogenic fungus with virulence factors for mammalian pathogenesis that also
      contribute to environmental survival. C. neoformans virulence may originate from
      selection pressures imposed by environmental predators.

PMID- 12787744
TI  - Systemic dissemination in tuberculosis and leprosy: do mycobacterial adhesins
      play a role?
AB  - More than one century after the discovery of their etiological agents,
      tuberculosis and leprosy remain as major health threats for humans, and the
      molecular mechanisms that lead to the development of both diseases are poorly
      understood. The elucidation of these mechanisms, and especially those allowing
      for the mycobacteria to systemically disseminate, should facilitate the
      development of new prophylactic and/or therapeutic strategies. This review is
      focused on the routes that Mycobacterium tuberculosis and Mycobacterium leprae
      may use to disseminate within the human body, and the potential roles played by
      recently characterized adhesins in this process.

PMID- 12787745
TI  - Sexual recombination and clonal evolution of virulence in Toxoplasma.
AB  - The protozoan parasite Toxoplasma gondii is endemic worldwide. For such a
      widespread pathogen that has few geographic or host boundaries, it possess an
      unexpected population structure comprised principally of three clonally
      propagated lineages. The origin and the evolutionary dynamics of these three
      lines are unclear. Recent population genetic analyses suggest that a meiotic
      recombination between two discrete gene pools produces a pandemic outbreak of
      three super-successful lines, which have recently come to dominate most other
      strains worldwide.

PMID- 12787746
TI  - A genomic view of lymphocyte development.
AB  - RNA expression profiles of consecutive stages of mouse and human B-cell
      precursors, and of mouse T-cell precursors, from DJ re-arranged states to mature
      lymphocytes have been generated using high-density oligonucleotide arrays.
      Approximately 10% of all genes present on the arrays are differentially expressed
      across all cellular stages of each of the lineages. Approximately half of these
      are differentially expressed during both T-cell and B-cell differentiation. Many
      of the genes that are shared are involved in cell cycle regulation and DNA
      replication, whereas most of the signaling and adhesion molecules and
      transcription factors are expressed in a lineage-specific manner. Comparable
      stages of the T-and B-lineage developmental programs share only a few genes. By
      contrast, homologous genes differentially expressed during both human and mouse B
      cell development have very similar expression patterns.

PMID- 12787748
TI  - The diversity of immunological synapses.
AB  - Immunological synapses (ISs) are specialised signalling domains characterised by
      complex molecular clustering and segregation at the contact site between cells of
      the immune system. T lymphocytes form different ISs depending on their state of
      activation and on the antigen-presenting cells with which they interact. The
      structural features of the various ISs are better established than the functions
      they carry out. Recent advances point to the importance of taking into account
      diversity in both the structures and the functions of IS.

PMID- 12787749
TI  - Lymphocyte lipid rafts: structure and function.
AB  - Evidence has accumulated over the past few years to suggest that specialized
      plasma membrane regions enriched in cholesterol and glycolipids, called 'lipid
      rafts', are primarily involved in the initiation and propagation of the signal
      transduction cascade associated with lymphocyte activation. Considering the
      multitude of recent and often contradictory data, however, it appears that a
      critical reconsideration of the role of lipid rafts in lymphocyte activation is
      necessary and timely, particularly in light of a series of new experimental
      results that challenge the traditional view of the role of lipid rafts in
      lymphocyte activation.

PMID- 12787750
TI  - Cytoskeletal remodeling in lymphocyte activation.
AB  - The formerly distinct fields of lymphocyte signal transduction and cytoskeletal
      remodeling have recently become linked, as proteins involved in transducing
      signals downstream of lymphocyte antigen receptors have also been implicated in
      actin cytoskeleton remodeling, microtubule dynamics and regulation of cell
      polarity. These discoveries have fuelled interest in understanding both the role
      of the actin cytoskeleton as an integral component of lymphocyte activation and
      the interplay between lymphoid cell-cell contact sites (immunological synapse),
      retractile pole structures (uropod, distal pole complex), and Rho-family GTPases
      (Rac, Rho, Cdc42), their upstream activators (Dbl-family guanine nucleotide
      exchange factors) and their downstream effectors (WASp, Arp2/3, ADAP). To
      understand how these complex regulatory networks are wired, a new breed of
      computational biologists uses mathematical language to reproduce and simulate
      signaling circuits 'in silico'.

PMID- 12787751
TI  - Adaptor proteins in lymphocyte activation.
AB  - Adaptor proteins are unique, as they contain modular domains and lack intrinsic
      enzymatic activity. These proteins are scaffolds for the organization of
      macromolecular complexes and they recruit other proteins for correct localization
      during molecular signal transduction. Numerous recent advances have been made
      through the elucidation of new adaptor proteins and the recognition of novel
      functions for previously identified molecules. In addition, the roles of adaptors
      in both the positive and negative regulation of lymphocyte activation have been
      further clarified.

PMID- 12787752
TI  - The SLAM family of immune-cell receptors.
AB  - The 'signalling lymphocyte activation molecule' (SLAM) family is a newly
      appreciated group of immune-cell specific receptors that has the ability to
      regulate the function of several immune cell types. Recent studies show that the
      SLAM-related receptors mediate intracellular protein tyrosine phosphorylation
      signals. This property is dependent on the aptitude of SLAM-family receptors to
      bind with high affinity to SAP and/or EAT-2, two small adaptor molecules composed
      almost exclusively of a Src homology 2 domain. SAP is mutated in X-linked
      lymphoproliferative disease, a human immune dysfunction characterised by an
      inappropriate response to Epstein-Barr virus infection, thereby suggesting that
      the SLAM-related receptors may be critical for a normal immune response. The
      existence of the SLAM family broadens the spectrum of receptors known to be
      involved in immunomodulation.

PMID- 12787753
TI  - Assembling atomic resolution views of the immunological synapse.
AB  - Antigen-dependent T-cell activation is initiated by the organized interactions of
      a host of cell-surface receptors in the interface between the T cell and an
      antigen-presenting cell. Recent structural studies of many of the receptors that
      comprise this 'immunological synapse', including integrins, cadherins and co
      stimulatory molecules, reveal in detail the molecular interactions that bridge
      the synapse. Additionally, structural analyses of the cytoplasmic tails of
      integrins and co-stimulatory receptors in complex with intracellular signaling
      proteins are providing insight into the mechanisms that couple receptor
      clustering on the cell surface with the initiation of cytoplasmic signaling.

PMID- 12787754
TI  - Regulation and function of serine kinase networks in lymphocytes.
AB  - Recent technological developments have facilitated explorations of the sustained
      signalling pathways important for lymphocyte activation. One key response
      necessary for lymphocyte activation is the prolonged activation of the lipid
      kinase phosphatidylinositol-3 kinase (PI3K). It has also been shown that there is
      sustained activation of diverse serine/threonine kinases in activated
      lymphocytes.

PMID- 12787755
TI  - Calcium signalling in lymphocytes.
AB  - The modulation of intracellular calcium ion concentration, [Ca(2+)](i), is a
      common signalling mechanism used in many biological systems. B and T lymphocytes
      rely on Ca(2+) signalling to initiate both developmental and activation programs.
      Recent data has shed new light on the initiation of this signalling pathway, the
      connection between the release of intracellular Ca(2+) stores and the influx of
      extracellular Ca(2+), and the molecular identity of the elusive Ca(2+) release
      activated Ca(2+) (CRAC) channel. In addition, recent gene profiling of T
      lymphocytes has identified the genes that are controlled by [Ca(2+)](i) and the
      Ca(2+)-dependent phosphatase calcineurin.

PMID- 12787756
TI  - Natural killer cell receptor signaling.
AB  - Natural killer (NK) cell immune responses are regulated by a balance of
      activating and inhibitory signals transmitted by cell surface receptors.
      Immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic domains of
      inhibitory NK receptors recruit tyrosine or lipid phosphatases, which modulate
      the activation signals transmitted by receptors linked to the Syk and ZAP70
      tyrosine kinases and phosphatidylinositol-3 kinases. In addition, recent studies
      of gene-deficient animals, in particular Syk and ZAP70 double-deficient mice,
      suggest that NK cells possess a robust and potentially redundant receptor system
      to ensure their development and function.

PMID- 12787758
TI  - Regulation of peripheral T-cell homeostasis by receptor signalling.
AB  - The peripheral T-cell pool is maintained at a constant size throughout life. This
      is achieved through tight homeostatic regulation of the different T-cell subsets.
      T cells appear to be able to sense whether the T-cell compartment is full and, if
      it is not, they are able to respond by undergoing cell division. Recent advances
      have identified that both signalling through the T-cell receptor and a variety of
      cytokines are essential for the regulation of these responses.

PMID- 12787757
TI  - Negative regulation of TCR signaling and T-cell activation by selective protein
      degradation.
AB  - Protein degradation was previously considered to be a nonspecific cellular
      process that eradicated abnormal or damaged proteins. Current evidence indicates,
      however, that T cells use this mechanism to selectively eliminate activated T
      cell receptors (TCRs) and signaling molecules, and consequently control the
      duration and specificity of TCR signaling.

PMID- 12787759
TI  - Cell-death signaling and human disease.
AB  - The autoimmune lymphoproliferative syndrome (ALPS) in humans and the lpr mouse
      strain are the first examples of primary apoptosis defects caused by inherited
      death-receptor mutations. They illustrate the role of Fas and Fas ligand in the
      control of autoimmune T-cell and B-cell proliferation. Subsequent analyses of
      ALPS in humans have highlighted the role of caspase 10 in the induction of
      apoptosis. The recent identification of a human caspase 8 defect has revealed a
      potential connection between apoptosis pathways and immune-receptor signaling.
      The genetic basis of ALPS is extremely complex, as multiple factors are
      potentially involved in the pathogenesis of this disease, thus offering an
      interesting model with which to unravel the mechanisms involved in T-cell
      homeostasis and self-tolerance.

PMID- 12787761
TI  - Heterogeneity of CD4(+) and CD8(+) T cells.
AB  - There is extensive plasticity in the T-cell response to antigen. Helper CD4(+) T
      cells, cytotoxic CD8(+) T cells, the progression from naive to effector and
      memory T cells, and differentiation into Th1, Tc1, Th2 and Tc2 subsets have long
      been recognized. More recently it has become apparent that T-cell populations
      display additional diversity in terms of phenotype, anatomical distribution and
      effector function.

PMID- 12787762
TI  - Migration and T-lymphocyte effector function.
AB  - The development of immunity depends upon the capacity of responding T cells to
      become mobilized from lymphoid tissues where they are primed to sites of antigen
      exposure, wherever they occur in the body. Activation-induced alterations in the
      ability of T cells to migrate signify a fundamental change in biological
      function. Considerable attention is now focused on identifying mechanisms that
      regulate the migration and persistence of T cells that disseminate to non
      lymphoid compartments as effector cells, and those that are retained in the
      lymphoid compartment. There are many unanswered questions about the developmental
      relationships and roles in protective immunity of antigen-experienced T cells
      that partition in different tissues.

PMID- 12787763
TI  - T-cell effector mechanisms: gammadelta and CD1d-restricted subsets.
AB  - Gammadelta T lymphocytes and CD1d-restricted natural killer T cells are
      classified as innate T lymphocytes, which perform effector functions that protect
      from malignancy and maintain tissue integrity. Innate T cells also play important
      regulatory roles in autoimmunity, inflammation and infection. Recent advances
      have established innate T cells as both effectors and regulators of disease in
      biological models.

PMID- 12787764
TI  - B cells as effectors.
AB  - B cells act as immune effectors, primarily through antigen-specific clonal
      expansion and plasma-cell differentiation. B1 (CD5(+)) B cells and marginal zone
      B cells dominate T-cell independent humoral responses under the molecular control
      of activated dendritic cells. Helper T cell-regulated B-cell responses draw on
      follicular B cells as precursors and rely on qualitatively different patterns of
      immune synapse formation to regulate B-cell fate. These activities culminate in
      the germinal center reaction, during which somatic hypermutation and antigen
      driven selection produce and preserve high-affinity plasma cells with extended
      longevity and memory B cells as the sensitized precursors for antigen recall.

PMID- 12787766
TI  - Genomic insulators: connecting properties to mechanism.
AB  - Insulators are regulatory elements that establish independent domains of
      transcriptional activity within eukaryotic genomes. Insulators possess two
      properties: an anti-enhancer activity that blocks enhancer-promoter
      communication, and an anti-silencer activity that prevents the spread of
      repressive chromatin. Some insulators are composite elements with separable
      activities, while others employ a single mechanism to confer both properties.
      Recent studies focus on elucidating the molecular mechanisms of insulator
      function. Emerging themes support connections between insulators, transcriptional
      activators and topological chromosomal domains. Understanding these processes
      will provide insights into prevention of inappropriate regulatory interactions,
      knowledge that can be applied to gene therapies.

PMID- 12787767
TI  - Maintenance of chromatin states: an open-and-shut case.
AB  - The traditional view of chromatin envisions two states: one is 'active' and
      accessible to nucleases, whereas the other is 'silent' and relatively
      inaccessible. Recent evidence that combinations of diverse histone tail
      modifications represent a spectrum of chromatin states challenges this simple
      view. Here, we examine inter-relationships between chromatin remodeling, histone
      modification, DNA methylation, RNA interference, and nucleosome assembly
      activities. We find that the two-state view can accommodate these new findings,
      and that nucleosome assembly pathways may ultimately maintain euchromatic and
      heterochromatic states.

PMID- 12787768
TI  - Telomerase: what are the Est proteins doing?
AB  - Saccharomyces cerevisiae has proven to be a useful model organism for the study
      of telomerase, a specialized cellular reverse transcriptase that helps maintain
      genomic stability by adding telomeric DNA repeats to the ends of chromosomes.
      Yeast telomerase is thought to be a holoenzyme containing Est2p and TLC1 RNA, the
      catalytic subunit and its intrinsic template, respectively, as well as the TLC1
      RNA-associated factors Est1p and Est3p. Cdc13p, a sequence-specific telomere-DNA
      binding protein, is also required for action in vivo. A current model for
      telomerase regulation is that telomere-associated Cdc13p binds Est1p, thereby
      recruiting telomerase. However, recent chromatin immunoprecipitation experiments
      suggest an alternate role for Est1p in activating Est2p-TLC1-RNA that is already
      bound to the telomere. Three models for Est1p activation are presented.

PMID- 12787769
TI  - Epigenetic gene regulation by noncoding RNAs.
AB  - Functional noncoding RNAs have distinct roles in epigenetic gene regulation.
      Large RNAs have been shown to control gene expression from a single locus (Tsix
      RNA), from chromosomal regions (Air RNA), and from entire chromosomes (roX and
      Xist RNAs). These RNAs regulate genes in cis; although the Drosophila roX RNAs
      can also function in trans. The chromatin modifications mediated by these RNAs
      can increase or decrease gene expression. These results suggest that the primary
      role of RNA molecules in epigenetic gene regulation is to restrict chromatin
      modifications to particular regions of the genome. However, given that RNA has
      been shown to be at the catalytic core of other ribonucleoprotein complexes, it
      is also possible that RNA also plays a role in modulating changes in chromatin
      structure.

PMID- 12787770
TI  - Reprogramming DNA methylation in the preimplantation stage: peeping with Dolly's
      eyes.
AB  - Oocyte cytoplasmic factors can reprogramme the sperm genome during fertilisation
      or the somatic cell genome during cloning. Diverse reprogramming machinery acts
      sequentially and interdependently on the imported genome to drive it to
      totipotency, but their three-dimensional interactions in the cytoplasm remain
      unknown. Aberrant epigenetic phenomena in early cloned embryos indicate that
      parts of the somatic cell genome are unyielding to reprogramming forces, owing to
      their 'knotty' epigenetic features. This fastidious nature of the donor genome
      might prevent completion of epigenetic reprogramming. It might also help to
      explain the chronic developmental defects seen in many cloned embryos.

PMID- 12787771
TI  - Targeting genes and transcription factors to segregated nuclear compartments.
AB  - With increasingly detailed images of nuclear structures revealed by advanced
      microscopy, a remarkably compartmentalized cell nucleus has come into focus.
      Although this complex nuclear organization remains largely unexplored, some
      progress has been made in deciphering the functional aspects of various
      subnuclear structures, revealing how this elaborate framework can influence gene
      activation. Several recent studies have helped illustrate how cells might utilize
      the nuclear architecture as an additional level of transcriptional control,
      perhaps by targeting genes and regulatory factors to specific sites within the
      nucleus that are designated for active RNA synthesis.

PMID- 12787772
TI  - Dynamics of chromatin, proteins, and bodies within the cell nucleus.
AB  - A new and still evolving paradigm of a highly dynamic nucleus has emerged in
      recent years. This paradigm includes an inherently high turnover rate of histone
      and non-histone protein modifications, targeted turnover and/or displacement of
      'stable' core histone proteins, constant flux of macromolecules through
      chromosomes and nuclear bodies, including transcription factors and co
      activators, and an energy-dependent facilitation of nuclear-protein complex
      formation and disassembly. Also included are fast, local movements of
      chromosomes, together with slower but long-range movements of chromosomes and
      nuclear bodies.

PMID- 12787773
TI  - The anatomy of transcription sites.
AB  - Patterns of gene expression in multicellular eukaryotes are regulated by numerous
      extremely sophisticated mechanisms. Over the past year, developments in our
      ability to monitor the organisation and dynamic properties of the components
      involved in gene expression have emphasised how both global nuclear architecture
      and chromosome structure can influence this fundamental process.

PMID- 12787774
TI  - The nucleolus: a site of ribonucleoprotein maturation.
AB  - The nucleolus is the site of ribosomal RNA synthesis, processing and ribosome
      maturation. Various small ribonucleoproteins also undergo maturation in the
      nucleolus, involving RNA modification and RNA-protein assembly. Such steps and
      other activities of small ribonucleoproteins also take place in Cajal (coiled)
      bodies. Events of ribosome biogenesis are found solely in the nucleolus, which is
      the final destination of small nucleolar RNAs after their traffic through Cajal
      bodies. However, nucleoli are just a stopping point in the intricate cellular
      traffic for small nuclear RNAs and other ribonucleoproteins.

PMID- 12787775
TI  - Coupling transcription, splicing and mRNA export.
AB  - Previous studies have led to the view that mRNAs are transported from the nucleus
      to the cytoplasm by machinery that is conserved from yeast to humans. Moreover,
      this machinery is coupled both physically and functionally to the pre-mRNA
      splicing machinery. During the past year, important new insights into the
      mechanisms behind this coupling have been made. In addition, recent advances have
      revealed mechanisms for the co-transcriptional loading of the export machinery on
      to mRNAs. Finally, a newly identified link between the nuclear exosome and the
      machineries required for transcription, 3'-end formation and mRNA export suggests
      that proper mRNP formation is co-transcriptionally monitored.

PMID- 12787776
TI  - Nuclear mRNA surveillance.
AB  - Recent studies demonstrate that the factors involved in mRNA processing specify
      the fate of a transcript. The mRNA is either committed for export to the
      cytoplasm or accumulates in the nucleus, where it may be degraded. These studies
      reveal crosstalk among the nuclear events faced by the pre-mRNA. It is becoming
      evident that the components of the mRNA synthesis machinery interact with each
      other to establish a distinct surveillance mechanism that determines release of
      the transcript from the transcription site for further export and utilisation.
      Recent advances suggest that the major nuclear decay machinery, the nuclear
      exosome, and an Rrp6p-specific complex coordinate with processing factors to
      perform a unique regulatory function that determines its fate: either confinement
      of the defective mRNA at its transcription site, or release from its site of
      transcription for further processing and export or decay. Furthermore, message
      specific regulatory mechanisms correspond with the nuclear mRNA synthesis
      machinery to control gene expression.

PMID- 12787777
TI  - The small GTPase Ran: interpreting the signs.
AB  - The small GTPase Ran has roles in nuclear transport, mitotic spindle assembly and
      nuclear envelope assembly. During the past three years, it has become clear that
      many of these processes rely on conserved molecular mechanisms involving Ran-GTP
      binding proteins of the importin-beta superfamily. Moreover, recent experimental
      evidence has documented the distribution of Ran-GTP within cells and supported
      the notion that Ran plays a central role in the spatial and temporal organization
      of the eukaryotic cell.

PMID- 12787778
TI  - The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA
      repair.
AB  - Interest in BRCA1 stems from its role as a tumour suppressor in breast and
      ovarian cancer. Intensive research in BRCA1 has revealed little about its
      specific role in cancer; rather, this protein has been implicated in a multitude
      of important cellular processes. The diverse biochemical activities of BRCA1
      combine to protect the genome from damage. New data reveal that BRCA1
      transcriptionally regulates some DNA-repair genes, and, in addition, new roles
      for BRCA1 have been identified in heterochromatin formation on the X chromosome,
      double-strand-break repair, and ubiquitination. These diverse activities of BRCA1
      may be linked in a single pathway, or BRCA1 might function in multiple nuclear
      processes.

PMID- 12787779
TI  - Regulation of p53 functions: let's meet at the nuclear bodies.
AB  - The p53 tumour suppressor is crucial for the ability of the cell to either arrest
      cell cycle progression or activate apoptosis in response to stimuli that may
      impinge on genomic stability. p53 activation is controlled by mechanisms
      involving post-translational modifications, protein interactions and modulation
      of subcellular localisation. Recently, p53 was identified within nuclear bodies,
      particular subnuclear structures that can provide a 'platform' where interaction
      of p53 with specific cofactors is favoured. Modulation of recruitment/release of
      some of these components and modifications might be required for directing p53
      toward one or another of its downstream response pathways.

PMID- 12787780
TI  - The nucleoskeleton: lamins and actin are major players in essential nuclear
      functions.
AB  - The nucleoskeleton is composed of many interacting structural proteins that
      provide the framework for DNA replication, transcription and a variety of other
      nuclear functions. For example, the type-V intermediate filament proteins, the
      lamins, and their associated proteins (e.g. Lap2alpha) play important roles in
      DNA replication and transcription. Furthermore, actin, actin-related proteins and
      other actin-associated proteins likewise appear to be important in nuclear
      functions because they are components of chromatin-remodeling complexes and are
      involved in mRNA synthesis, processing and transport. Newly described nuclear
      proteins that contain both actin- and lamin-binding domains could be involved in
      regulating molecular crosstalk between these two types of nucleoskeletal
      proteins. This range of activities might help to explain why genetic defects in
      some of the nucleoskeletal proteins contribute to an ever-expanding list of human
      diseases.

PMID- 12787783
TI  - The laminopathies: nuclear structure meets disease.
AB  - Most inherited diseases are associated with mutations in a specific gene.
      Sometimes, mutations in two or more different genes result in diseases with a
      similar phenotype. Rarely do different mutations in the same gene result in a
      multitude of seemingly different and unrelated diseases. In the past three years,
      different mutations in LMNA, the gene encoding the A-type lamins, have been shown
      to be associated with at least six different diseases. These diseases and at
      least two others caused by mutations in other proteins associated with the
      nuclear lamina are collectively called the laminopathies. How different tissue
      specific diseases arise from unique mutations in the LMNA gene, encoding almost
      ubiquitously expressed nuclear proteins, are providing tantalizing insights into
      the structural organization of the nucleus, its relation to nuclear function in
      different tissues and the involvement of the nuclear envelope in the development
      of disease.

PMID- 12787784
TI  - Muscular dystrophies: genes to pathogenesis.
AB  - Muscular dystrophies are a genetically heterogeneous group of degenerative muscle
      disorders. Nearly 30 genes are known to give rise to various forms of muscular
      dystrophy, which differ in age of onset, severity, and muscle groups affected.
      The number of genes identified increases each year, adding to our understanding
      as well as revealing the overall complexity of the pathogenesis of these
      diseases.

PMID- 12787785
TI  - Transcriptional derepression as a cause of genetic diseases.
AB  - Transcription of DNA into mRNA is a highly regulated process directed by a
      complex molecular machine comprising more than 100 proteins. Regulation of
      transcription occurs by both positive (transcriptional activation) and negative
      (transcriptional repression) mechanisms. Recently, inappropriate transcriptional
      derepression has been found as the underlying basis of several human genetic
      diseases. The putative target genes, whose inappropriate expression is thought to
      cause disease, have remained elusive but are being searched for intensively.

PMID- 12787786
TI  - Chromatin remodeling and human disease.
AB  - In the past few years, there has been a nascent convergence of scientific
      understanding of inherited human diseases with epigenetics. Identified epigenetic
      processes involved in human disease include covalent DNA modifications, covalent
      histone modifications, and histone relocation. Each of these processes influences
      chromatin structure and thereby regulates gene expression and DNA methylation,
      replication, recombination, and repair. The importance of these processes for
      nearly all aspects of normal growth and development is illustrated by the array
      of multi-system disorders and neoplasias caused by their dysregulation.

PMID- 12787787
TI  - Protein aggregation and the ubiquitin proteasome pathway: gaining the UPPer hand
      on neurodegeneration.
AB  - Protein misfolding and aggregation are common to most neurodegenerative diseases,
      suggesting that abnormalities of protein homeostasis contribute to pathogenesis.
      Research implicates at least two components of cellular protein quality control
      in disease: molecular chaperones and the ubiquitin-proteasome pathway (UPP).
      Although evidence is more compelling for chaperone involvement, recent cell-based
      and genetic studies suggest that perturbations in the UPP also contribute to
      neurodegenerative disease processes. UPP involvement in disease seems even more
      probable when the UPP is viewed not simply as an isolated degradation machine but
      rather as a complex cascade linked both to other ubiquitin-dependent processes
      and to chaperone systems.

PMID- 12787788
TI  - Nuclear genes in mitochondrial disorders.
AB  - Nuclear genes encode hundreds of proteins involved in mitochondrial biogenesis
      and oxidative phosphorylation (OXPHOS). Nevertheless, the identification of
      nuclear genes responsible for OXPHOS-related disorders has proceeded at a much
      slower pace, compared with the discovery and characterization of mtDNA mutations.
      Reasons for such a gap include rarity of syndromes, genetic heterogeneity, and
      ignorance on this nuclear gene repertoire in humans. This scenario is changing
      rapidly, thanks to the discovery of several OXPHOS-related human genes, and to
      the identification in some of them of disease-associated mutations. In addition,
      new strategies - based on transcriptome and proteome analysis, and functional
      complementation assays - have been applied successfully to mitochondrial
      medicine.

PMID- 12787789
TI  - The mammalian circadian clock.
AB  - Organisms populating the earth are under the steady influence of daily and
      seasonal changes resulting from the planet's rotation and orbit around the sun.
      This periodic pattern most prominently manifested by the light-dark cycle has led
      to the establishment of endogenous circadian timing systems that synchronize
      biological functions to the environment. The mammalian circadian system is
      composed of many individual, tissue-specific clocks. To generate coherent
      physiological and behavioral responses, the phases of this multitude of clocks
      are orchestrated by the master circadian pacemaker residing in the
      suprachiasmatic nuclei of the brain. Genetic, biochemical and genomic approaches
      have led to major advances in understanding the molecular and cellular basis of
      mammalian circadian clock components and mechanisms.

PMID- 12787790
TI  - Rodent models of genetic disease.
AB  - The genetic study of rats and mice using natural variants, natural mutations,
      chemical or radiation induced mutations, engineered mutations and conditional
      engineered mutations has provided the tools for investigating the genetics of
      disease. The completion of the mouse genomic sequence and progress towards
      sequencing the rat genome in the past year will enable the molecular
      identification of quantitative trait loci and induced mutations. Sequence-based
      single nucleotide polymorphism discovery and a greater understanding of the
      haplotype structure of inbred strains is revitalising quantitative trait locus
      mapping and there are now plans for an ambitious eight-way recombinant inbred
      cross and renewed interest in existing resources such as heterogeneous stocks. In
      the past year there have been refinements to ENU mutagenesis approaches including
      balancer chromosomes and a new gene-driven approach.

PMID- 12787791
TI  - Human and mouse disorders of pigmentation.
AB  - Disorders of pigmentation were among the first genetic diseases ever recognized
      because of their visually striking clinical phenotypes, resulting from defects of
      pigmentary melanocytes. Recent years have seen remarkable progress in
      understanding these diseases, largely as a result of the systematic parallel
      study of human patients and inbred mice with similar phenotypes. Our
      understanding of disorders of pigmentation indicates that these diseases may be
      most usefully considered as abnormalities of melanocyte development, function, or
      survival.

PMID- 12787792
TI  - Modifier genes and protective alleles in humans and mice.
AB  - Interest in modifier genes is growing rapidly because of their ability to
      modulate the phenotype of individuals with monogenic and multigenic traits and
      diseases. A neglected class of modifiers is protective alleles that can suppress
      disease in otherwise susceptible individuals. Together these modifier genes and
      protective alleles provide important glimpses into the molecular and cellular
      basis for the functional networks that provide robustness and homeostasis in
      complex biological systems.

PMID- 12787793
TI  - Finding genes underlying risk of complex disease by linkage disequilibrium
      mapping.
AB  - Identification of genes that harbor variation associated with inter-individual
      differences in risk of complex diseases remains one of the most challenging and
      important problems in human genetics. For genetic variants that are sufficiently
      common and have sufficiently large effects, direct tests of association through
      linkage disequilibrium with anonymous SNPs may prove effective. But the two
      critical parameters - the frequency of risk-inflating alleles and the magnitudes
      of their effect on risk - remain largely unknown. In this review we consider the
      latest information regarding the likely efficacy of the linkage disequilibrium
      mapping approach.

PMID- 12787794
TI  - Genetics and genomics of behavioral and psychiatric disorders.
AB  - Psychiatric conditions are to some degree under genetic influences. Despite the
      application of advanced genetic and molecular biological technologies, the
      genetic bases of the human behavioral traits and psychiatric diseases remains
      largely unresolved. Conventional genetic linkage approaches have not yielded
      definitive results, possibly because of the absence of objective diagnostic
      tests, the complex nature of human behavior or the incomplete penetrance of
      psychiatric traits. However, recent studies have revealed some genes of interest
      using multifaceted approaches to overcome these challenges. The approaches
      include using families in which specific behaviors segregate as a mendelian
      trait, utilization of endophenotypes as biological intermediate traits,
      identification of psychiatric disease phenotypes in genomic disorders, and the
      establishment of mouse models.

PMID- 12787795
TI  - The use of telomere probes to investigate submicroscopic rearrangements
      associated with mental retardation.
AB  - Idiopathic mental retardation is a common condition the origins of which are
      poorly understood. Following initial reports that small chromosomal
      rearrangements affecting telomeres could be an important aetiological
      contributor, several new methods for screening patients have been developed. Over
      the past few years, 22 studies have reported results from 2585 patients. The
      prevalence of abnormalities in the entire group is 5.1%; but the figure is higher
      (6.8%) in individuals with moderate to severe mental retardation. About half the
      cases are caused by a de novo deletion, and about half by a balanced
      translocation segregating in a patient's family. Despite the large sample size
      available, it is still not clear whether a combination of thorough clinical
      examination and assiduous cytogenetic investigation might not be as effective at
      detecting subtelomeric anomalies as molecular assays.

PMID- 12787796
TI  - Gene therapy for ocular neovascularization: a cure in sight.
AB  - Recent advances in the field of ocular gene transfer have led researchers
      pursuing treatment for age-related macular degeneration and diabetic retinopathy
      to turn to gene therapy for the answer. Viral vector-mediated delivery of both
      anti-angiogenic proteins and molecules that inhibit the eye's endogenous pro
      angiogenic factors has successfully diminished the pathology of ocular diseases
      in rodent models. A gene-therapy solution to the debilitating blindness caused by
      ocular neovascularization may be on the horizon.

PMID- 12787797
TI  - Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis.
AB  - Connective tissue growth factor (CTGF/CCN2) is a highly profibrogenic molecule
      which is overexpressed in many fibrotic lesions, including those of the liver.
      CTGF/CCN2 is transcriptionally activated by transforming growth factor-beta (TGF
      beta) and appears to mediate some of the extracellular matrix (ECM)-inducing
      properties that have been previously attributed to TGF-beta. CTGF/CCN2 and TGF
      beta stimulate connective tissue cell proliferation and ECM synthesis in vitro
      and exhibit shared fibrogenic and angiogenic properties in vivo. In fibrotic
      liver, CTGF/CCN2 mRNA and protein are produced by fibroblasts, myofibroblasts,
      hepatic stellate cells (HSCs), endothelial cells, and bile duct epithelial cells.
      CTGF/CCN2 is also produced at high levels in hepatocytes during cytochrome P
      4502E1-mediated ethanol oxidation. CTGF/CCN2 expression in cultured HSCs is
      enhanced following their activation or stimulation by TGF-beta while exogenous
      CTGF/CCN2 is able to promote HSC adhesion, proliferation, locomotion, and
      collagen production. Collectively, these data suggest that during initiating or
      downstream fibrogenic events in the liver, production of CTGF/CCN2 is regulated
      primarily by TGF-beta in one or more cell types and that CTGF/CCN2 plays
      important roles in HSC activation and progression of fibrosis. This article
      reviews the data that support the importance of CTGF/CCN2 in hepatic fibrosis and
      highlights the concept that CTGF/CCN2 may represent a new therapeutic target in
      this disease.

PMID- 12787798
TI  - Efficacy of a glycyrrhizin suppository for the treatment of chronic hepatitis C:
      a pilot study.
AB  - Intravenous administration of glycyrrhizin has potential efficacy on decreasing
      serum aminotransferase levels in patients with chronic hepatitis. However,
      patients receiving this treatment are recommended to attend hospital regularly
      for several years. To improve the quality of life for these patients, we
      developed a glycyrrhizin suppository. In this pilot study, we examined the most
      effective and safe material contents of the suppository and revealed clinical
      efficacy for patients with biopsy-proven chronic hepatitis C comparing
      intravenous administration of glycyrrhizin. As content combinations of the
      suppository, a mixture of 300 mg of glycyrrhizinic ammonium salt and 60 &mgr;g of
      sodium capric acid, with pH neutralization, was confirmed to be most effective
      and safe condition, based on analysis of serum glycyrrhizin levels and the grade
      of rectal irritations in tested patients. The efficacy on decreasing serum
      alanine aminotransferase levels for 12-week administration of the suppository in
      13 patients with chronic hepatitis C was similar to that in another 13 patients
      intravenously administered glycyrrhizin. Moreover, no serious side effects were
      observed. In conclusion, the usage of the newly developed suppository of
      glycyrrhizin can improve the quality of life for chronic hepatitis C patients,
      especially those who do not respond with viral clearance to interferon therapy.
      Using this suppository, larger and longer-term studies are needed.

PMID- 12787799
TI  - Hepatitis C virus infection upregulates expression of the type I interferon
      receptor in human peripheral blood mononuclear cells.
AB  - To assess whether hepatitis C virus infection (HCV) affects type I interferon
      (IFN) receptor expression, the expression levels of two subunits of this
      receptor, IFNAR1 and IFNAR2, in peripheral blood mononuclear cells (PBMCs) were
      determined by flow-cytometric assay in 68 anti-HCV antibody-positive patients (47
      positive for HCV RNA and 21 negative for HCV RNA) and 14 healthy controls. The
      percentages of IFNAR1- and IFNAR2-expressing cells were significantly higher in
      HCV RNA-positive patients than in HCV RNA-negative patients or healthy controls.
      In multiple regression analysis, the presence of HCV RNA in serum was
      independently associated with the expression of both IFNAR1 and IFNAR2 in PBMCs
      (P=0.007 for IFNAR1 and P=0.003 for IFNAR2). The frequency of IFN-gamma-producing
      peripheral CD4(+) and CD8(+) cells was also significantly higher in HCV RNA
      positive patients than in HCV RNA-negative patients or healthy controls and there
      was a significant correlation between IFN receptor expression and the frequency
      of IFN-gamma-producing cells. These results suggest that HCV infection
      upregulates the expression of the type I IFN receptor in PBMCs through enhanced
      IFN-gamma production by peripheral CD4(+) and CD8(+) cells as one of mechanisms
      that regulate the expression of the type I IFN receptor.

PMID- 12787800
TI  - Serum platelet-activating factor acetylhydrolase (PAF-AH) activity in patients
      with hyperbilirubinemic hepatobiliary disease.
AB  - Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme that catalyzes
      hydrolysis of PAF and is important for regulation of serum PAF concentration.
      Twenty-seven patients with hyperbililubinemic hepatobiliary diseases (eight
      patients with liver cirrhosis, five with acute hepatitis and 14 with obstructive
      cholestasis) were studied. Serum PAF-AH activity was elevated in
      hyperbilirubinemic condition associated with liver cirrhosis, obstructive
      cholestasis or acute hepatitis. There was a significant correlation of serum PAF
      AH activity with serum cholesterol (r=0.891, P=0.014 in liver cirrhosis, r=0.813,
      P=0.002 in obstructive cholestasis) or low density lipoprotein (LDL) cholesterol
      (r=0.771, P=0.007 in obstructive cholestasis). Serum PAF-AH activity/cholesterol
      ratio and PAF-AH activity/LDL cholesterol ratio were elevated in the three types
      of hyperbilirubinemic liver disease. LDL cholesterol increased and PAF-AH/LDL
      cholesterol ratio decreased in acute hepatitis after remission. On the other
      hand, LDL cholesterol decreased and PAF-AH/LDL cholesterol ratio did not change
      after treatment in obstructive cholestasis. These findings suggest that, though
      serum LDL is a factor influencing serum PAF-AH activity in obstructive jaundice,
      other factors, i.e. reduced biliary PAF-AH excretion, may also influence serum
      PAF-AH activity in hyperbilirubinemic hepatobiliary diseases.

PMID- 12787801
TI  - Reduced urinary 6beta-hydroxycortisol to cortisol ratios in patients with liver
      cirrhosis.
AB  - While the urinary concentration ratio of 6beta-hydroxycortisol (6beta-HC) to
      cortisol (C) in 24-h urine samples is an established parameter for the induction
      of hepatic cytochrome P450 (CYP) 3A activity, it remains unclear whether it would
      be reduced in association with chronic liver damages. To clarify this issue we
      measured this parameter in 12 patients with chronic hepatitis, 15 patients with
      liver cirrhosis and 12 healthy subjects. Urinary 6beta-HC and C were assayed with
      high-performance liquid chromatography with ultraviolet absorption. Multiple
      regression analysis was performed to search for which biochemical or demographic
      parameter(s) would be associated with the overall variability of urinary 6beta
      HC/C ratios. Results showed that the mean (+/-S.D.) 6beta-HC/C ratio obtained
      from the patients with liver cirrhosis (4.3+/-2.6), but not that from patients
      with chronic hepatitis (7.4+/-7.2), was significantly (P<0.05) lower than that
      obtained from the healthy controls (11.8+/-8.3). It was also revealed that among
      the clinical parameters examined (e.g. serum transaminases concentrations) only
      serum albumin concentrations were correlated significantly (R=0.61, P<0.05) with
      the urinary 6beta-HC/C ratio. In conclusion, the present study implies that that
      the reduced urinary 6beta-HC/C ratios in patients with liver cirrhosis may be
      associated with attenuated hepatic CYP3A activity in these patients.

PMID- 12787802
TI  - 1,25-Dihydroxyvitamin D(3) induced cell cycle arrest in the human primary liver
      cancer cell line HepG2.
AB  - The inhibitory effect of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on the
      proliferation of a number of human and rat liver cancer cell lines has recently
      been reported. In this study we have demonstrated that these cell lines express
      functional receptors able to specifically bind [3H]1,25-(OH)(2)D(3). The highest
      level of functional receptor were found in the human liver cancer cell line HepG2
      which had previously been shown to be the most sensitive in 1,25-(OH)(2)D(3)
      growth inhibition assays. The identity of the binding protein with the Vitamin D3
      receptor was confirmed by PCR analysis of HepG2 cell mRNA. Additionally, the
      inhibitory effect of 1,25-(OH)(2)D(3) on growth of the human liver cancer cell
      line HepG2 resulted from arrest in the G0/G1 phase of the cell cycle. Increases
      in the fraction of cells in G0/G1 were dependent upon the concentration of 1,25
      (OH)(2)D(3) and were accompanied by complementary decreases in the number of
      cells in S phase. There was no change in the number of cells in G2+M at any
      concentration of the hormone. Clonal growth of HepG2 cells in response to 1,25
      (OH)(2)D(3) was also dose dependent over three orders of magnitude, thus
      indicating heterogeneity in cell cycle arrest by this hormone.

PMID- 12787803
TI  - A new suppressive agent against interleukin-1beta and tumor necrosis factor-alpha
      enhances liver regeneration after partial hepatectomy in rats.
AB  - In the present study, the effect of FR167653, a novel suppressive agent against
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), on
      liver regeneration was investigated in rats after partial hepatectomy (PH). Doses
      of 1, 3 and 5 mg/kg per h FR167653 (FR-1, FR-3 and FR-5, respectively) were given
      intravenously 30 min before PH, while the control was given normal saline. Serum
      chemistries were serially monitored, and liver regeneration was evaluated by
      remnant liver weight ratio, proliferating cell nuclear antigen (PCNA) labeling
      index and mitotic index. Accumulation of IL-1beta and TNF-alpha messenger RNA
      (mRNA) in the remnant liver was also measured. In FR167653-treated groups, the
      releases of alanine transaminase (ALT) and aspartate transaminase (AST) were
      lower. The PCNA labeling index was enhanced by FR167653-administration in a dose
      dependent manner, FR-3 and FR-5 groups showed significantly higher peak DNA
      synthesis than the control group at 24 h post-PH (P<0.01). The mitotic index was
      also enhanced by FR167653-administration in a dose-dependent manner. In FR-5
      group, the remnant liver weight ratio was significantly higher than that in the
      control group (P<0.05). The accumulation of IL-1beta messenger RNA (mRNA) in the
      remnant liver was obviously suppressed in FR-3 and FR-5 groups, but the
      expression of TNF-alpha mRNA was not apparently reduced. In conclusion, FR167653
      ameliorates liver injury and enhances liver regeneration after PH in rats.

PMID- 12787804
TI  - Aspirin induces hepatoma-derived cell apoptosis via a hydrogen peroxide-dependent
      pathway.
AB  - Here we studied whether aspirin (ASA) has any influence on viability of human
      hepatoma-derived SKHep-1 cells and whether hydrogen peroxide (H(2)O(2)) has any
      relation with this effect. ASA inhibited SKHep-1 cell proliferation dose- and
      time-dependently. Intracellular H(2)O(2) increased as early as 15 min after ASA
      supplementation. Cellular apoptosis correlated with an increase in intracellular
      H(2)O(2) level. Moreover, in the presence of a catalase inhibitor-aminotriazol,
      ASA showed more apoptotic effect on SKHep-1 cells with increasing intracellular
      H(2)O(2) level. In conclusion, the present results shows that ASA induced SKHep-1
      cell apoptosis has a relation with an early increase in intracellular H(2)O(2)
      level and catalase inhibitor synergizes to induce this process.

PMID- 12787805
TI  - A monoclonal antibody to rat asialoglycoprotein receptor that recognizes an
      epitope specific to its major subunit.
AB  - We previously developed three mouse monoclonal antibodies (MoAbs) identifying the
      domain-specific plasma membrane proteins of rat hepatocytes. Based on the results
      of immunohistochemical and immunoblot analysis, one of them, clone 8D7, likely
      recognizes the rat asialoglycoprotein receptor (ASGPR), which consists of three
      polypeptide subunits: rat hepatic lectin (RHL)-1, RHL-2 and RHL-3. In this study,
      we examined the reactivity of MoAb 8D7 with these subunits in order to identify
      specifically the protein it recognizes. RHL-1 and RHL-2/3 were expressed in COS-1
      mammalian kidney cells transfected with cloned cDNAs. Reactivity of MoAb 8D7 with
      these proteins was examined by flow cytometry, immunoblotting, and an
      immunofluorescence staining. By flow cytometry, MoAb 8D7 reacted with cell
      surface proteins on the COS-1 cells transfected with RHL-1 cDNA but not with RHL
      2/3 cDNA. By immunoblotting, the antibody recognized proteins (molecular weights
      45 and 96 kDa) in RHL-1-expressing cells but not in the RHL-2/3 cDNA-transfected
      cells. Immunoreactive staining with MoAb 8D7 was observed on the cell surface and
      in the cytoplasm of RHL-1-transfected COS-1 cells but not in cells expressing RHL
      2/3. These findings indicate that MoAb 8D7 recognizes a subunit-specific epitope
      on RHL-1 of rat ASGPR.

PMID- 12787806
TI  - Inability of liver dendritic cells from mouse with experimental hepatitis to
      process and present specific antigens.
AB  - The functions of resident antigen-presenting cells (APC) may be compromised in
      inflammatory microenvironment of the host. However, little is known regarding the
      phenotype and function of the liver resident APC in this condition. This issue
      was addressed by evaluating the function of liver dendritic cells (DC) from mice
      with concanavalin-A-induced experimental hepatitis. In sharp contrast to normal
      mice, the expressions of MHC class II and CD86 antigens were not upregulated on
      liver DC from mice with hepatitis due to interactions with specific antigens like
      hepatitis B surface antigen and keyhole limpet hemocyanin. Accordingly, these DC
      were completely unable to induce proliferation of antigen-specific memory
      lymphocytes. Moreover, liver DC from mice with hepatitis produced significantly
      lower levels of interleukin-12 and interferon-gamma compared with those from
      control mice. The lack of antigen internalization capacity of liver DC from mice
      with hepatitis was evident from their low endocytosis capacity. These data
      indicate that impaired antigen capturing and T cell activating capacity of liver
      DC may contribute to low magnitude of antigen-specific immune responses in mice
      with experimental hepatitis.

PMID- 12787807
TI  - Effectiveness of carbohydrate-restricted diet and arginine granules therapy for
      adult-onset type II citrullinemia: a case report of siblings showing homozygous
      SLC25A13 mutation with and without the disease.
AB  - Case 1 is a 37-year-old Japanese man who was admitted to this hospital with a
      disturbance of consciousness. A diagnosis of adult-onset type II citrullinemia
      was made by DNA analysis of SLC25A13 (851del4/851del4) and measurement of hepatic
      ASS activity (2% of control value). After regaining consciousness, Case 1 was
      started on a dietary therapy, revealing that hypertriglyceridemia and ketogenesis
      impairment deteriorated on a low-protein diet and ameliorated on a carbohydrate
      restricted (high-protein) diet. Case 1 could tolerate 70 g/day of protein while
      using arginine granules and developed hyperammonemia only after discontinuation
      of the administration. Case 2 (an elder brother of Case 1) is also homozygote for
      the same SLC25A13 mutation. The hepatic activity of argininosuccinate synthetase
      was about 20% of the control value. However, Case 2 exhibited neither
      hyperammonemia nor lipid metabolism abnormalities. These results suggest that,
      although adult-onset type II citrullinemia is caused by a deficiency of citrin,
      which plays key roles in carbohydrates, amino acids and even lipid metabolism,
      some other environmental or genetic factors are required for the onset of the
      disease, and from the authors' clinical experience, a carbohydrate-restricted
      (relatively high-protein) diet is advocated as a benefit to the patients, and
      that arginine granules are indispensable to this new dietary therapy.

PMID- 12787808
TI  - Spontaneous rupture of peripancreatic lymph node with hepatocellular carcinoma
      metastasis: report of an autopsy case with massive peritoneal bleeding.
AB  - Hepatocellular carcinoma (HCC) has a tendency for fatal spontaneous rupture
      leading to massive hemorrhage. The majority of such ruptures of HCC occur in the
      liver, while a few previous studies showed that such HCC rupture developed at
      metastatic sites including the lung, pleura, spleen, and peritoneum. We here
      report a case of hepatitis C virus-related HCC with spontaneous rupture of a
      peripancreatic lymph node with HCC metastases. A 61-year-old Japanese man died of
      hepatic failure after therapy for cirrhosis and HCC for 6 years. At autopsy, the
      liver showed diffuse multinodular HCC in both lobes. Metastases were found in
      lumbar vertebral bones and abdominal lymph nodes of the hepatic hilar,
      peripancreatic and perigastric regions. One lymph node (4 cm in diameter) around
      the pancreatic head was found ruptured, and blood coagula (100 g) was present
      around the ruptured node. Pure blood of 2000 ml was noted in the peritoneal
      cavity. Cirrhosis was not recognized. Histologically, the liver tumors and
      metastases in the lumbar vertebral bones and abdominal lymph nodes were poorly
      differentiated HCC of Edmondson's grade III. The ruptured lymph node was almost
      replaced by poorly-differentiated HCC, and the ruptured site showed hemorrhage,
      breakdown of the capsule, and ischemic changes. Non-tumorous liver showed chronic
      hepatitis C. The immediate cause of death was suggested to be circulatory
      insufficiency due to rupture of the lymph node and/or hepatic failure. The
      present case showed that abdominal lymph nodes with HCC metastases may rupture
      and cause severe hemorrhage in the peritoneal cavity, leading to death.

PMID- 12787809
TI  - Lamivudine therapy for hepatitis B virus reactivation in a patient receiving
      intra-arterial chemotherapy for advanced hepatocellular carcinoma.
AB  - We describe a case of hepatitis B virus (HBV) reactivation that responded to
      lamivudine therapy in a 58-year-old man with advanced hepatocellular carcinoma
      (HCC). After seroconversion of hepatitis B e antigen to e antibodies by
      interferon therapy, the patient was found to have HCC with a portal tumor
      thrombus. A transarterial port was placed in the right femoral artery to permit
      infusion of epirubicin and cisplatin. After 3 months of arterial chemotherapy,
      the serum alpha-fetoprotein level had decreased and tumor staining diminished.
      Laboratory examinations suggested a flare-up of hepatitis B. Lamivudine was given
      to manage HBV reactivation. After 1 month, the serum HBV DNA level fell below the
      detection limit, and the alanine aminotransferase activity decreased to the
      normal range. With further arterial chemotherapy for HCC, no tumor staining was
      detected on computed tomography. Administration of lamivudine decreased serum HBV
      DNA levels for 7 months. Our findings suggest that HBV may be reactivated during
      chemotherapy for HCC, similar to other types of malignancies, and that lamivudine
      is effective for the management of HBV reactivation.

PMID- 12787810
TI  - Pitfalls of enzyme-based molecular anticancer dietary manipulations: food for
      thought.
AB  - Dietary approaches to cancer chemoprevention increasingly have focused on single
      nutrients or phytochemicals to stimulate one or another enzymatic metabolizing
      system. These procedures, which aim to boost carcinogen detoxification or inhibit
      carcinogen bioactivation, fail to take into account the multiple and paradoxical
      biological outcomes of enzyme modulators that make their effects unpredictable.
      Here, we critically examine the scientific and medical evidence for the idea that
      the physiological roles of specific enzymes may be manipulated by regular, long
      term administration of isolated nutrients and other chemicals derived from food
      plants. Instead, we argue that consumption of healthful diets is most likely to
      reduce mutagenesis and cancer risk, and that research efforts and dietary
      recommendations should be redirected away from single nutrients to emphasize the
      improvement of dietary patterns as a principal strategy for public health policy.

PMID- 12787811
TI  - Illusions of safety: antimutagens can be mutagens, and anticarcinogens can be
      carcinogens.

PMID- 12787812
TI  - Beta-carotene: a cancer chemopreventive agent or a co-carcinogen?
AB  - Evidence from both epidemiological and experimental observations have fueled the
      belief that the high consumption of fruits and vegetables rich in carotenoids may
      help prevent cancer and heart disease in humans. Because of its well-documented
      antioxidant and antigenotoxic properties, the carotenoid beta-carotene (betaCT)
      gained most of the attention in the early 1980s and became one of the most
      extensively studied cancer chemopreventive agents in population-based trials
      supported by the National Cancer Institute. However, the results of three
      randomized lung cancer chemoprevention trials on betaCT supplementation
      unexpectedly contradicted the large body of epidemiological evidence relating to
      the potential benefits of dietary carotenoids. Not only did betaCT show no
      benefit, it was associated with significant increases in lung cancer incidence,
      cardiovascular diseases, and total mortality. These findings aroused widespread
      scientific debate that is still ongoing. It also raised the suspicion that betaCT
      may even possess co-carcinogenic properties. In this review, we summarize the
      current data on the co-carcinogenic properties of betaCT that is attributed to
      its role in the induction of carcinogen metabolizing enzymes and the over
      generation of oxidative stress. The data presented provide convincing evidence of
      the harmful properties of this compound if given alone to smokers, or to
      individuals exposed to environmental carcinogens, as a micronutrient supplement.
      This has now been directly verified in a medium-term cancer transformation
      bioassay. In the context of public health policies, while the benefits of a diet
      rich in a variety of fruits and vegetables should continue to be emphasized, the
      data presented here point to the need for consideration of the possible
      detrimental effects of certain isolated dietary supplements, before mass cancer
      chemoprevention clinical trials are conducted on human subjects. This is
      especially important for genetically predisposed individuals who are
      environmentally or occupationally exposed to mutagens and carcinogens, such as
      those found in tobacco smoke and in industrial settings.

PMID- 12787813
TI  - How many high production chemicals are rodent carcinogens? Why should we care?
      What do we need to do about it?
AB  - High production volume (HPV) chemicals are produced in or imported to the US in
      amounts greater than 1 million pounds per chemical per year. The EPA has
      identified thousands of HPVs. Due to their abundance, such chemicals bring a
      substantial risk for human exposure, and as a result some level of adverse
      consequences to health are to be expected. In order to examine the potential for
      cancer risk associated with HPVs, this paper examines HPVs that have been tested
      in the National Toxicology Program's rodent cancer bioassay. The chemicals tested
      in the bioassay represent a small sample of the universe of environmental
      chemicals to which people are exposed. Unexpectedly, 60% of the 128 HPVs
      evaluated in the bioassay proved to be rodent carcinogens. This value compares to
      a predicted prevalence of only 16.5% carcinogens in a previous study. The
      previous study concluded that HPVs were less likely to be toxic by a variety of
      other test criteria as well. However, the approach involved identifying putative
      carcinogens using quantitative chemical structure-activity relationships (QSAR)
      in contrast to the direct tabulation of bioassay test results performed here.
      Detailed examination of bioassay results reveals that test outcomes depend
      heavily on route of administration as well as on dose level, sex, strain, and
      species used. Since most of these factors have little or no apparent relationship
      to chemical structure, results of this study suggest that QSAR, as well as
      virtually all other alternative methods, may not generally provide accurate
      predictions of carcinogenic potential. As we wait for efficient and effective
      methods for predicting carcinogens to be developed, people continue to be exposed
      to environmental carcinogens. Progress on regulating environmental carcinogens as
      well as on developing more effective test methods has been minimal since "war on
      cancer" began approximately 30 years ago. The present study questions whether the
      current strategy for dealing with environmental carcinogens will ever be
      successful. Close examination of rodent cancer test results seems to suggest that
      almost all chemicals may have carcinogenic potential in some genotypes under some
      exposure circumstances. If this hypothesis is correct, it would explain the
      general lack of progress in developing methods to differentiate carcinogens from
      noncarcinogens. A completely new strategy for dealing with cancer caused by
      exposures to environmental chemicals seems to be needed.

PMID- 12787814
TI  - Biological sample collection and processing for molecular epidemiological
      studies.
AB  - Molecular epidemiology uses biomarkers and advanced technology to refine the
      investigation of the relationship between environmental exposures and diseases in
      humans. It requires careful handling and storage of precious biological samples
      with the goals of obtaining a large amount of information from limited samples,
      and minimizing future research costs by use of banked samples. Many factors, such
      as tissue type, time of collection, containers used, preservatives and other
      additives, transport means and length of transit time, affect the quality of the
      samples and the stability of biomarkers and must be considered at the initial
      collection stage. An efficient study design includes provisions for further
      processing of the original samples, such as cryopreservation of isolated cells,
      purification of DNA and RNA, and preparation of specimens for cytogenetic,
      immunological and biochemical analyses. Given the multiple uses of the samples in
      molecular epidemiology studies, appropriate informed consent must be obtained
      from the study subjects prior to sample collection. Use of barcoding and
      electronic databases allow more efficient management of large sample banks.
      Development of standard operating procedures and quality control plans is a
      safeguard of the samples' quality and of the validity of the analyses results.
      Finally, specific state, federal and international regulations are in place
      regarding research with human samples, governing areas including custody, safety
      of handling, and transport of human samples, as well as communication of study
      results.Here, we focus on the factors affecting the quality and the potential
      future use of biological samples and some of the provisions that must be made
      during collection, processing, and storage of samples, based on our experience in
      the Superfund Basic Research Program and Children's Environmental Health Center,
      at the University of California, Berkeley.

PMID- 12787815
TI  - The evolution of cell death programs as prerequisites of multicellularity.
AB  - One of the hallmarks of multicellularity is that the individual cellular fate is
      sacrificed for the benefit of a higher order of life-the organism. The accidental
      death of cells in a multicellular organism results in swelling and membrane
      rupture and inevitably spills cell contents into the surrounding tissue with
      deleterious effects for the organism. To avoid this form of necrotic death the
      cells of metazoans have developed complex self-destruction mechanisms,
      collectively called programmed cell death, which see to an orderly removal of
      superfluous cells. Since evolution never invents new genes but plays variations
      on old themes by DNA mutations, it is not surprising, that some of the genes
      involved in metazoan death pathways apparently have evolved from homologues in
      unicellular organisms, where they originally had different functions.
      Interestingly some unicellular protozoans have developed a primitive form of non
      necrotic cell death themselves, which could mean that the idea of an altruistic
      death for the benefit of genetically identical cells predated the invention of
      multicellularity. The cell death pathways of protozoans, however, show no
      homology to those in metazoans, where several death pathways seem to have evolved
      in parallel. Mitochondria stands at the beginning of several death pathways and
      also determines, whether a cell has sufficient energy to complete a death
      program. However, the endosymbiotic bacterial ancestors of mitochondria are
      unlikely to have contributed to the recent mitochondrial death machinery and
      therefore, these components may derive from mutated eukaryotic precursors and
      might have invaded the respective mitochondrial compartments. Although there is
      no direct evidence, it seems that the prokaryotic-eukaryotic symbiosis created
      the space necessary for sophisticated death mechanisms on command, which in their
      distinct forms are major factors for the evolution of multicellular organisms.

PMID- 12787816
TI  - Genotoxicity of pesticides: a review of human biomonitoring studies.
AB  - Pesticides constitute a heterogeneous category of chemicals specifically designed
      for the control of pests, weeds or plant diseases. Pesticides have been
      considered potential chemical mutagens: experimental data revealed that various
      agrochemical ingredients possess mutagenic properties inducing mutations,
      chromosomal alterations or DNA damage. Biological monitoring provides a useful
      tool to estimate the genetic risk deriving from an integrated exposure to a
      complex mixture of chemicals. Studies available in scientific literature have
      essentially focused on cytogenetic end-points to evaluate the potential
      genotoxicity of pesticides in occupationally exposed populations, including
      pesticide manufacturing workers, pesticide applicators, floriculturists and farm
      workers. A positive association between occupational exposure to complex
      pesticide mixtures and the presence of chromosomal aberrations (CA), sister
      chromatid exchanges (SCE) and micronuclei (MN) has been detected in the majority
      of the studies, although a number of these failed to detect cytogenetic damage.
      Conflicting results from cytogenetic studies reflect the heterogeneity of the
      groups studied with regard to chemicals used and exposure conditions. Genetic
      damage associated with pesticides occurs in human populations subject to high
      exposure levels due to intensive use, misuse or failure of control measures. The
      majority of studies on cytogenetic biomarkers in pesticide-exposed workers have
      indicated some dose-dependent effects, with increasing duration or intensity of
      exposure. Chromosomal damage induced by pesticides appears to have been transient
      in acute or discontinuous exposure, but cumulative in continuous exposure to
      complex agrochemical mixtures. Data available at present on the effect of genetic
      polymorphism on susceptibility to pesticides does not allow any conclusion.

PMID- 12787817
TI  - Measuring the mitotic index in chemically-treated human lymphocyte cultures by
      flow cytometry.
AB  - In the human lymphocyte chromosome aberration assay, the mitotic index (MI) is
      the standard cytotoxic parameter for determining which test concentrations will
      be evaluated for chromosome aberrations. Assessment of the MI is performed
      microscopically by determining the frequency of mitotic cells in a population of
      1000 cells. With the commercial availability of antibodies to the mitosis
      specific marker, phosphorylated-histone H3 at serine 10, automating the
      assessment of the MI using flow cytometry is now possible [Cytometry 32 (1998)
      71]. Our laboratory has utilized and validated this technology to measure the
      mitotic index of chemically-treated human lymphocyte cultures. Comparisons
      between the microscopic and flow MI frequencies from 24h treatments with
      mitomycin-C, aphidicolin, eugenol, etoposide, hydroxyrurea, potassium cyanide,
      staurosporine, ethyl alcohol, noscapine and colcemid((R)) are presented. Our
      results show that the mitosis specific H3-P marker is excellent for measuring the
      MI frequency in human lymphocyte cultures treated up to toxic concentrations. In
      addition, this study demonstrates that automation of analysis by flow cytometry
      is an excellent alternative to the microscopic method of analysis producing less
      variability than the microscopic scoring and a more complete dose response curve.

PMID- 12787819
TI  - Sister chromatid exchanges and micronuclei analysis in lymphocytes of men exposed
      to simazine through drinking water.
AB  - In some cities of the autonomous community of Extremadura (south-west of Spain),
      levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the
      possible effect of this herbicide, two biomarkers, sister chromatid exchanges
      (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males
      exposed to simazine through drinking water. SCE and MN analysis failed to detect
      any statistically significant increase in the people exposed to simazine when
      compared with the controls. With respect to high frequency cells (HFC), a
      statistically significant difference was detected between exposed and control
      groups.

PMID- 12787818
TI  - Sperm-FISH analysis and human monitoring: a study on workers occupationally
      exposed to styrene.
AB  - Occupational exposure to styrene, a chemical extensively used worldwide, is under
      investigation for possible detrimental effects on human health, including male
      reproductive capacity. Aneuploidy in germ cells is the main cause of infertility,
      abortions and congenital diseases. Fluorescence in situ hybridisation (FISH), is
      the most efficient cytogenetic molecular technique to date to analyse numerical
      alterations of chromosomes in spermatozoa. We investigated the frequencies of
      aneuploidy and diploidy in individuals occupationally exposed to styrene and in
      healthy unexposed controls. We performed multicolour FISH, using DNA probes
      specific for the centromeric regions of sex chromosomes and chromosome 2, in
      decondensed sperm nuclei of samples with normal semen parameters for a total of
      18 styrene-exposed subjects and 13 unexposed controls of the same age range.
      Exposed individuals had worked for at least 2 years during the last 5 years, and
      continuously for 6 months, in factories producing reinforced plastics. The
      incidence of aneuploidy and diploidy for the tested chromosomes did not show a
      statistically significant difference between workers and controls. The exposure
      to styrene was associated with increased frequencies of nullisomy for sex
      chromosomes in the group of non-smokers, although only a limited number of
      subjects belonged to this sub-group. Considering the whole study population, age
      was associated with an increased frequency of XX disomy, whereas smoking was
      associated with meiosis II non-disjunction of sex chromosomes. Overall,
      confounding factors appeared to exert a more important effect than exposure to
      styrene on numerical chromosome alterations in sperm nuclei of subjects selected
      for normal semen parameters.

PMID- 12787820
TI  - Characterization of cytotoxic and genotoxic effects of different compounds in CHO
      K5 cells with the comet assay (single-cell gel electrophoresis assay).
AB  - Different variants of the comet assay were used to study the genotoxic and
      cytotoxic properties of the following eight compounds: chloral hydrate,
      colchicine, hydroquinone, DL-menthol, mitomycin C, sodium iodoacetate, thimerosal
      and valinomycin. Colchicine, mitomycin C, sodium iodoacetate and thimerosal
      induced genotoxic effects. The other compounds were found to be inactive. The
      compounds were tested in the standard comet assay as well as in the all cell
      comet assay (recovery of floating cells after treatment), designed in our
      laboratory for adherently-growing cells. This latter procedure proved to be more
      adequate for the assessment of the cytotoxicity for some of the compounds tested
      (hydroquinone, DL-menthol, thimerosal, valinomycin). Colchicine was positive in
      the standard comet assay (3h treatment) and in the all cell comet assay (24h
      treatment). Sodium iodoacetate and thimerosal were positive in the standard
      and/or the all cell comet assay. Chloral hydrate, hydroquinone, sodium
      iodoacetate, mitomycin C and thimerosal were also tested in the modified comet
      assay using lysed cells. Mitomycin C and thimerosal showed effects in this assay,
      whereas sodium iodoacetate was inactive. This indicates that it does not induce
      direct DNA damage. Compounds that are known or suspected to form DNA-DNA cross
      links or DNA-protein cross-links (chloral hydrate, hydroquinone, mitomycin C and
      thimerosal) were checked for their ability to reduce ethyl methanesulfonate (EMS)
      induced DNA damage. This mode of action could be demonstrated for mitomycin C
      only.

PMID- 12787821
TI  - Inhibition of clastogenicity of benzo[a]pyrene and of its trans-7,8-dihydrodiol
      in mice in vivo by fruits, vegetables, and flavonoids.
AB  - In the in vivo mouse bone marrow micronucleus assay, homogenates of spinach,
      artichoke, peaches, and blue grapes as well as commercial concentrates of these
      vegetables and fruits reduced induction of micronuclei by benzo[a]pyrene (BaP) by
      43-50%. Concentrates of strawberries (31% reduction) and of cauliflower (20%
      reduction) were less potent. Inhibition of genotoxicity by spinach and peaches
      was not caused by any delay in maturation of micronucleated erythrocytes as shown
      by experiments with sampling times of 24, 48, and 72 h after dosing of BaP. Pre
      treatment of the mice with spinach 48, 24, and 12h before application of BaP
      resulted in a 44% reduction of micronuclei while peaches generated only a
      marginal effect. A post-treatment procedure administering spinach or peaches 6h
      after dosing of BaP did not indicate any protective effects. When trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene (BaP-7,8-OH) was applied for induction of
      micronuclei spinach and peaches reduced the number of micronuclei by 55 and 48%,
      respectively. Pre-treatment of mice with spinach 96, 72, and 60 h before
      sacrifice caused a decline of hepatic 7-ethoxyresorufin-O-dealkylase (EROD) and
      of 7-pentoxyresorufin-O-dealkylase (PROD) activities by factors of 2.2 and 1.4,
      respectively. However, statistical significance was not reached. On the other
      hand, peaches had no influence on hepatic EROD or PROD activities. The flavonoids
      quercetin and its glucoside isoquercitrin, administered orally in doses of 0.03
      mmol/kg body weight simultaneously with intraperitoneally given BaP, reduced the
      number of micronuclei in polychromatic erythrocytes of the bone marrow of mice by
      73 and 33%. Ten-fold higher concentrations, however, reversed the effects with a
      particular strong increase observed with isoquercitrin (+109%; quercetin: +16%).

PMID- 12787822
TI  - An assessment of the genotoxicity of 2-hydroxy-1,4-naphthoquinone, the natural
      dye ingredient of Henna.
AB  - 2-Hydroxy-1,4-naphthoquinone (HNQ; Lawsone; CAS 83-72-7) is the principal natural
      dye ingredient contained in the leaves of Henna (Lawsonia inermis). Published
      genotoxicity studies on HNQ suggested it was a weak bacterial mutagen for
      Salmonella typhimurium strain TA98 or was more clearly mutagenic for strain TA
      2637, both in the presence of metabolic activation. HNQ was unable to induce sex
      linked recessive lethal mutations in Drosophila melanogaster. However, a small
      increase in micronucleus frequency was reported in the bone marrow of mice at a
      single mid-range dose level, 24h after intraperitoneal injection. In view of the
      wide use of Henna hair dyes it was deemed necessary to conduct a thorough
      investigation, under Good Laboratory Practice conditions, of the genotoxicity of
      HNQ. HNQ was non-mutagenic in bacterial (Ames test) or mammalian (V79 hprt)
      assays. It was borderline positive in a mouse lymphoma tk mutation assay and a
      chromosome aberration test (CHO cells), results that may reflect a similar
      clastogenic mechanism. Negative in vivo genotoxicity results were noted in the
      rat hepatocyte in vivo/in vitro UDS test, in peripheral lymphocytes (chromosome
      aberrations) of rats receiving repeated oral doses of HNQ at the MTD for 28 days,
      and in mouse and hamster bone marrow chromosome aberration tests. However small,
      but statistically significant increases in the incidence of bone marrow
      micronuclei were observed in two out of five tests at 72 h after dosing, but not
      at 24 or 48 h. There was evidence of haematotoxicity at 72 h, which may have been
      enhanced by the vehicle (DMSO) used in the positive tests. As erythropoiesis and
      administration of haematotoxic agents are known to induce small increases in the
      frequency of bone marrow micronuclei, typically at delayed sampling times, the
      data suggest that the positive 72 h response produced by HNQ is consistent with
      stimulation of haematopoiesis subsequent to haematological toxicity of HNQ, and
      not due to a DNA-reactive mechanism. Overall, the weight of evidence suggests
      that Henna and HNQ pose no genotoxic risk to the consumer.

PMID- 12787823
TI  - The unusual effect of pKM101 on the mutagenicity of acetaldehyde oxime in
      Salmonella typhimurium.
AB  - Acetaldehyde oxime was found to induce more revertants in Salmonella typhimurium
      strain TA1535 than in TA100 in the absence of S9 metabolic activation. TA100 was
      originally constructed from TA1535 by the addition of the plasmid pKM101,
      carrying mucAB which generally enhances sensitivity to the mutagenic effects of
      chemicals. The role of pKM101 in lowering the sensitivity to acetaldehyde oxime
      was explored by: (1) increasing the incubation time of the selective agar plates
      from 2 to 3 days; (2) using a new strain, isogenic to TA100, constructed by
      introducing pKM101 into the TA1535 isolate used in these experiments; (3) by
      testing a strain constructed by inserting into TA1535 a plasmid carrying mucAB
      but otherwise unrelated to pKM101. Each of these alterations increased the number
      of revertants per plate in the presence of acetaldehyde oxime, indicating that
      the apparent nonmutagenicity of this chemical in TA100 is due to multiple
      factors.

PMID- 12787824
TI  - NF449, a novel picomolar potency antagonist at human P2X1 receptors.
AB  - The antagonistic effects of the novel suramin analogue 4,4',4",4"'
      (carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3
      disulfonic acid (NF449) were analyzed at homomeric human P2X(1) and P2X(7)
      receptor subtypes (hP2X(1) and hP2X(7)) heterologously expressed in Xenopus
      oocytes using the two-microelectrode voltage-clamp technique. At activating ATP
      concentrations of 1 microM (hP2X(1)) and 100 microM (hP2X(7)), IC(50) values of
      0.05 nM and 40 microM were found for hP2X(1) and hP2X(7) receptors, respectively.
      The Schild analysis revealed a pA(2) of 10.7 at hP2X(1). Wash-in and wash-out of
      10 nM NF449 were nearly complete within 16 s and 4 min, respectively, at the
      hP2X(1) receptor. An increase in the activating ATP concentration to 100 microM
      shifted the NF449 concentration-inhibition curve rightwards for the hP2X(1)
      receptor. NF449 decelerated activation as well as desensitization of hP2X(1). It
      is concluded that NF449 acts as a reversible competitive antagonist at the
      hP2X(1) with much higher potency at hP2X(1) than at hP2X(7) receptors. NF449 may
      hence be excellently suited to discriminate between both receptors in native
      human tissues.

PMID- 12787825
TI  - Negative modulation of L-type Ca2+ channels via beta-adrenoceptor stimulation in
      guinea-pig detrusor smooth muscle cells.
AB  - beta-Adrenergic stimulation enhances the activity of L-type Ca(2+) channels
      through mechanisms mediated by adenosine 3'5'-cyclic monophosphate (cAMP) and
      protein kinase A in cardiac myocytes. However, in smooth muscle cells, the effect
      of beta-adrenoceptor stimulation on the L-type Ca(2+) channel activity has been
      controversial, and the exact mechanism is still unclear. The present study was
      aimed at elucidating the effect of beta-adrenergic stimulation upon the activity
      of L-type Ca(2+) channels in guinea-pig detrusor smooth muscle cells.
      Isoproterenol (0.1-1 microM) inhibited Ba(2+) currents through L-type Ca(2+)
      channels (I(Ba)). Isoproterenol (0.1 microM) shifted the steady-state
      inactivation curve to negative voltages by 11 mV without affecting activation
      curves. The stimulation of cAMP-mediated signal transduction pathway by
      forskolin, 8-bromoadenosine 3'5'-cyclic monophosphate (8-Br-cAMP), or the
      intracellular application of cAMP also mimicked the effects of isoproterenol on
      I(Ba), which was blocked by the inhibition of protein kinase A. These results
      indicate that, in detrusor smooth muscles, the stimulation of beta-adrenoceptors
      exerts negative modulation of L-type Ca(2+) channels via cAMP/protein kinase A
      dependent mechanism.

PMID- 12787826
TI  - Pharmacological sensitivity and gene expression analysis of the tibial nerve
      injury model of neuropathic pain.
AB  - The tibial nerve injury model is a novel, surgically uncomplicated, rat model of
      neuropathic pain based on a unilateral transection (neurotomy) of the tibial
      branch of the sciatic nerve. The aim of the present study was to describe some
      behavioral and molecular features of the model, and to test its sensitivity to a
      number of drugs which are currently used for the treatment of neuropathic pain.
      The model was characterized by a pronounced mechanical allodynia which was
      present in all subjects and a less robust thermal hyperalgesia. Mechanical
      allodynia developed within 2 weeks post-surgery and was reliably present for at
      least 9 weeks. Neurotomized rats showed no autotomy and their body weight
      developed normally. Gene expression in ipsilateral L5 dorsal root ganglia,
      analyzed by quantitative polymerase chain reaction (PCR), showed a pronounced up
      regulation of galanin and vasointestinal peptide (VIP). This up-regulation
      developed rapidly (within 1 to 2 days following neurotomy) and remained present
      for at least 12 days. On the other hand, expression of calcitonin gene-related
      peptide (CGRP) and substance P mRNA was down-regulated 12 days following
      neurotomy. Mechanical allodynia was completely reversed by morphine [minimal
      effective dose (MED): 8 mg/kg, i.p.] and partially reversed by carbamazepine
      (MED: 64 mg/kg, i.p.), baclofen (MED: 3 mg/kg, i.p.) and amitriptyline (trend for
      efficacy at 32 mg/kg, i.p.), but not by gabapentin (50-100 mg/kg, i.p.). The
      finding that the tibial nerve injury model shows a robust and persistent
      mechanical allodynia which is sensitive to a number of established analgesics, as
      well as a gene expression profile which is compatible with that obtained in other
      models of neuropathic pain, further supports its validity as a reliable and
      surgically uncomplicated model for the study of neuropathic pain.

PMID- 12787827
TI  - Spinally mediated analgesia and receptor binding affinity of epibatidine analogs.
AB  - Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo
      [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for
      their spinally mediated analgesic effects and binding affinity to nicotinic
      acetylcholine receptors. The tail flick response and behavioral side effects were
      studied after intrathecal agents in rats. The membrane preparations of the
      Torpedo Californica and rat cerebral cortices were used for radioligand binding
      utilizing [3H] epibatidine displacement. Their affinity to muscular and neuronal
      nicotinic acetylcholine receptors and spinally mediated analgesic potencies were
      15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less
      than epibatidine, respectively. Two times the analgesic 50% effective doses
      (ED(50)s) of the analogs did not induce side effects, while one-third of that of
      epibatidine induced motor disturbance. In summary, the two epibatidine analogs
      have higher potency ratio of spinally mediated analgesia/side effects than
      epibatidine.

PMID- 12787828
TI  - Long-term voluntary ethanol drinking increases expression of NMDA receptor 2B
      subunits in rat frontal cortex.
AB  - Forced ethanol drinking for several days and application of ethanol to cell
      cultures changes expression levels of various NMDA receptor subunits in rodents.
      Therefore, we investigated the influence of long-term voluntary ethanol
      consumption on the expression of NMDA receptor 2B (NR2B) subunits in several
      forebrain regions of rats [corrected]. This result is in accordance with and
      extends findings from studies using high doses of ethanol for a short period and
      suggests that the NR2B might be a potential target for an effective treatment of
      alcoholic patients.

PMID- 12787829
TI  - Nantenine blocks muscle contraction and Ca2+ transient induced by noradrenaline
      and K+ in rat vas deferens.
AB  - The effect of nantenine, an aporphine alkaloid isolated from Ocotea macrophylla
      H.B.K., was studied on contractions and Ca(2+) translocation induced by
      noradrenaline, Ca(2+), or K(+) in the isolated rat vas deferens from reserpinized
      animals. Concentration-response curves of calcium chloride (CaCl(2)) were
      performed in the vas deferens, in a Ca(2+)-free nutrient solution, using
      potassium chloride (KCl, 80 mM) as a depolarizing agent. In these conditions,
      nantenine (2.35 x 10(-4) and 4.7 x 10(-4) M) significantly reduced the maximum
      contractions (E(max)) of Ca(2+) (IC(50)=2.6 x 10(-4) M) and noradrenaline
      (IC(50)=2.9 x 10(-4) M). The contractile responses were totally recovered after
      the withdrawal of nantenine. In addition, experiments performed to measure
      simultaneously the contraction and the increase of intracellular Ca(2+) induced
      by noradrenaline (10(-5) M) or KCl (80 mM) showed that nantenine (2.35 x 10(-4)
      and 4.7 x 10(-4) M) significantly decreased both effects. The results suggest
      that a reversible block of Ca(2+) entry could be involved on the non-competitive
      like antagonism of nantenine in rat vas deferens.

PMID- 12787830
TI  - An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and
      spontaneously hypertensive rats.
AB  - The vascular response to most neurotransmitters of different vascular beds is
      altered under hypertensive condition. The modulatory effect of genetic pulmonary
      arterial hypertension on histamine responses is not known. The present study was
      undertaken to evaluate the modulatory effect of enzymatic degradation (via
      histamine N-methyl-transferase and diamine oxidase) on the vascular response of
      histamine, and the subtype(s) of histamine receptor present in the pulmonary
      artery (first branch, O.D. approximately 800 microm) of the normotensive Wistar
      Kyoto (WKY) and spontaneously hypertensive rats (SHR) (male, 22-26 weeks old). In
      phenylephrine (1 microM) pre-contracted preparations, histamine and 6-[2-(4
      imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT, a
      histamine H(1) receptor agonist) elicited a concentration-dependent relaxation,
      with a smaller magnitude recorded in SHR. Application of 10 microM S-[4-(N,N
      dimethylamino)-butyl]isothiourea (SKF 91488, a selective histamine N-methyl
      transferase inhibitor), but not aminoguanidine (100 microM, a diamine oxidase
      inhibitor), significantly attenuated histamine-induced relaxation. Clobenpropit
      (1 nM, a potent histamine H(3) receptor antagonist) "antagonised" the suppressive
      effect of SKF 91488 and histamine-evoked relaxation was restored. Endothelial
      denudation reduced histamine- and abolished HTMT-elicited relaxation. Dimaprit (a
      histamine H(2) receptor agonist) caused an endothelium-independent, cis-N-(2
      phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 microM, an
      adenylate cyclase inhibitor)-sensitive, concentration-dependent relaxation, with
      a similar magnitude in both strains of rat. Histamine-evoked relaxation was
      reversed into a further contraction (clobenpropit (10 nM)-sensitive) (with a
      greater magnitude occurred in the WKY rat) after blocking the histamine H(1) and
      H(2) receptors with diphenhydramine plus cimetidine (30 microM each). A similar
      further contraction (clobenpropit-sensitive) was observed with imetit (a
      histamine H(3)/H(4) receptor agonist) (> or =3 microM). Under resting tension,
      imetit (> or =0.3 microM) caused a clobenpropit (10 nM)- and prazosin (1 microM)
      sensitive, concentration-dependent contraction, with a greater contraction in the
      WKY rats. Our results suggest that inhibition of histamine catabolism using SKF
      91488 (histamine N-methyl-transferase inhibitor) resulted in a reduction of
      histamine-mediated relaxation that was due to the activation of the clobenpropit
      sensitive, histamine H(3)/H(4) receptor and the release of catecholamine. In
      addition, activation of histamine H(1) and H(2) receptors resulted in relaxation
      whereas histamine H(3)/H(4) receptor activation by imetit yielded a prazosin
      sensitive contraction of the pulmonary artery.

PMID- 12787831
TI  - Relaxant effect of YM976, a novel phosphodiesterase 4 inhibitor, on bovine
      tracheal smooth muscle.
AB  - Effects of 4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one
      (YM976), a novel and selective phosphodiesterase type 4 inhibitor, on tension and
      adenosine 3',5'-cyclic monophosphate (cAMP) content of bovine tracheal smooth
      muscle were compared with those of rolipram and theophylline. YM976, rolipram and
      theophylline relaxed the tracheal preparations contracted with histamine in a
      concentration-dependent manner. The relaxant effects of YM976 and rolipram were
      more potent than those of theophylline. These phosphodiesterase inhibitors
      induced relaxations were dramatically diminished when tracheal smooth muscle was
      contracted with methacholine instead of histamine. Pretreatment of the tracheal
      preparations with YM976 (10 microM) or rolipram (10 microM), but not with
      theophylline (1 mM), shifted the concentration-response curves for contractile
      responses to histamine; however, the same procedure failed to affect
      concentration-response relationships for methacholine-induced contractions. At 1
      and 10 microM, both YM976 and rolipram increased the tissues cAMP content. These
      results suggest that YM976 relaxes tracheal smooth muscle, probably through the
      cAMP-dependent mechanism.

PMID- 12787832
TI  - Lidocaine attenuates muscarinic receptor-mediated inhibition of adenylyl cyclase
      in airway smooth muscle.
AB  - We examined how lidocaine affects muscarinic receptor-mediated inhibition of
      adenylyl cyclase in bovine tracheal smooth muscles. Lidocaine (100 microM)
      augmented the relaxant responses to forskolin in the bovine tracheal smooth
      muscle contracted with methacholine (0.3 microM). On the other hand, lidocaine
      failed to affect the relaxant effects of forskolin on the histamine (100 microM)-
      and KCl (40 mM)-contracted preparations. Lidocaine (100 microM) enhanced both
      basal and forskolin-stimulated cAMP accumulation in the presence of methacholine
      (0.3 microM). However, in the absence of methacholine, neither basal nor
      forskolin-stimulated cAMP accumulation was affected by lidocaine. Similar
      phenomenon was observed when the bovine tracheal smooth muscles were treated with
      methoctramine (0.03 microM). In radioligand binding experiments, lidocaine
      inhibited [3H]N-methyl scopolamine binding to cloned human muscarinic receptors
      (M(1)-M(5)) expressed in Chinese hamster ovary cells. These results suggest that
      lidocaine prevents muscarinic receptor-mediated signaling pathway and thereby
      reverses inhibition of adenylyl cyclase by methacholine in bovine tracheal smooth
      muscle.

PMID- 12787833
TI  - Effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2 alpha on the release
      of noradrenaline from the isolated rat stomach.
AB  - In the present experiment, we examined the effect of 8-iso-prostaglandin E(2) and
      8-iso-prostaglandin F(2 alpha) on the release of noradrenaline from the isolated
      rat stomach. The postganglionic sympathetic nerves were electrically stimulated
      twice at 1 Hz for 1 min and test reagents were added during the second
      stimulation. 8-Iso-prostaglandin E(2) (10(-8)-10(-6) M) and 8-iso-prostaglandin
      F(2 alpha) (10(-7)-10(-5) M) dose-dependently reduced the evoked noradrenaline
      release, and these inhibitory potencies were as follows: 8-iso-prostaglandin
      E(2)>8-iso-prostaglandin F(2 alpha). The inhibitory effect of 8-iso-prostaglandin
      F(2 alpha), but not 8-iso-prostaglandin E(2), was abolished by 10(-6) M SQ-29548
      ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-7-[3-[[2
      [(phenylamino)carbonyl]hydrazino] methyl]-7-oxabicyclo[2,2,1]hept-2-yl]-5
      heptenoic acid) (a prostanoid TP receptor antagonist). On the other hand, the
      inhibitory effect of 8-iso-prostaglandin E(2) was abolished by 10(-5) M AH-6809
      (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) (a prostanoid EP receptor
      antagonist), which also attenuated the inhibitory effects of ONO-AE-248 (16S-9
      deoxy-9 beta-chloro-15-deoxy-16-hydroxy-17,17-trimethylene 19, 20-didehydro
      prostaglandin F(2)) (a selective EP(3) receptor agonist) on the evoked release of
      noradrenaline. The inhibitory effect of 8-iso-prostaglandin F(2 alpha), but not 8
      iso-prostaglandin E(2), was abolished by pertussis toxin. These results suggest
      that 8-iso-prostaglandin F(2 alpha) inhibits noradrenaline release through TP
      receptors, whereas 8-iso-prostaglandin E(2) seems to inhibit noradrenaline
      release through EP(3) receptors, located on the gastric sympathetic nerve
      terminals in rats.

PMID- 12787834
TI  - Thienylhydrazone derivative increases sarcoplasmic reticulum Ca2+ release in
      mammalian skeletal muscle.
AB  - 3,4-Methylenedioxybenzoyl-2-thienylhydrazone (L-294) is a cardiac inotropic drug
      whose action is mediated by an increase in intracellular Ca(2+) concentration as
      a result of enhanced Ca(2+) accumulation in the sarcoplasmic reticulum. In the
      present study we tested whether this new thienylhydrazone derivative was
      effective in mammalian skeletal muscle. We investigated the effect of L-294 on
      the contractility of isolated skeletal muscle, on Ca(2+) uptake and release by
      sarcoplasmic reticulum in skinned fibers and in membrane vesicles. L-294
      increased in a dose-dependent manner tension of isolated rat soleus muscle. In
      skinned type I fibers, L-294 induced tension and did not alter sarcoplasmic
      reticulum loading with Ca(2+). L-294 reduced the threshold Ca(2+) to induce
      Ca(2+) release and did not affect the ATP-dependent accumulation of Ca(2+) by
      sarcoplasmic reticulum vesicles. These results suggest that L-294 is an inotropic
      agent in skeletal muscle through an increase in the amount of Ca(2+) released
      from the sarcoplasmic reticulum.

PMID- 12787835
TI  - Histamine H1 receptor antagonism by cetirizine in isolated guinea pig tissues:
      influence of receptor reserve and dissociation kinetics.
AB  - We characterised histamine H(1) receptor antagonism by cetirizine and its
      enantiomers on isolated guinea pig ileum and trachea. Competitive or mixed
      (competitive and apparent noncompetitive) antagonism profiles were observed. The
      order of potency was: chlorpheniramine> or =mepyramine>levocetirizine>cetirizine>
      or =terfenadine>loratadine>dextrocetirizine. The inhibitory effects of
      cetirizine, levocetirizine, terfenadine and loratadine were slowly reversible
      compared to those of dextrocetirizine or mepyramine. Cetirizine and its
      enantiomers were inactive on L-type Ca(2+) channels. Reduction of the histamine
      H(1) receptor reserve by dibenamine in the ileum (100-fold higher than in the
      trachea) showed a gradual change from the competitive profile of dextrocetirizine
      and mepyramine to a mixed profile. The present results show that cetirizine and
      levocetirizine are selective competitive but slowly reversible histamine H(1)
      receptor antagonists. Their mixed antagonism profile observed in the trachea can
      be explained by the small receptor reserve present in this tissue compared to the
      ileum and their very slow dissociation rate from the histamine H(1) receptor.

PMID- 12787836
TI  - The effect of the GABAB receptor agonist baclofen on liquid and solid gastric
      emptying in mice.
AB  - The effect of the GABA(B) receptor agonist baclofen, a potential treatment for
      gastroesophageal reflux, on gastric emptying has not been determined. The effect
      of 1-4 mg/kg baclofen on liquid and solid gastric emptying in mice was evaluated
      by noninvasive [13C] breath tests. Baclofen accelerated gastric emptying of
      solids but delayed emptying of liquid, suggesting that it may have differential
      effects on proximal and distal stomach emptying.

PMID- 12787837
TI  - Role of endothelin ETA and ETB receptors in the guinea-pig urinary bladder
      contraction.
AB  - The distribution and function of endothelin receptors in the guinea-pig urinary
      bladder were examined. Specific [125I]endothelin-1 binding sites with both the
      endothelin ET(A) and ET(B) receptor subtypes were distributed in the muscle
      layer. Endothelin-1 elicited a tonic contraction which was inhibited by cyclo(D
      Asp-Pro-D-Val-Leu-D-Trp) (BQ123) but not by N-cis-2,6-dimethylpiperidinocarbonyl
      L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ788) and
      which was inhibited more strongly by a combination of BQ123 and BQ788.
      Sarafotoxin S6c elicited a contraction which was abolished by BQ788. The
      concentration of endothelin-1 in the muscle layer was 707.0+/-67.5 pg/g wet
      weight. Thus, endothelin-1 may regulate muscle tone via both subtypes of
      endothelin receptors in an autocrine manner in the guinea-pig urinary bladder.

PMID- 12787838
TI  - Thearubigin, the major polyphenol of black tea, ameliorates mucosal injury in
      trinitrobenzene sulfonic acid-induced colitis.
AB  - Inflammatory bowel disease is characterized by oxidative and nitrosative stress,
      leukocyte infiltration and upregulation of proinflammatory cytokines. The aim of
      the present study was to examine the protective effects of thearubigin, an anti
      inflammatory and anti-oxidant beverage derivative, on 2,4,6-trinitrobenzene
      sulfonic acid (TNBS)-induced colitis in mice, a model for inflammatory bowel
      disease. Intestinal lesions (judged by macroscopic and histological score) were
      associated with neutrophil infiltration (measured as increase in myeloperoxidase
      activity in the mucosa), increased serine protease activity (may be involved in
      the degradation of colonic tissue) and high levels of malondialdehyde (an
      indicator of lipid peroxidation). Both nitric oxide (NO) and O(2)(-) were
      increased with concomitant upregulation in the mRNA expression of proinflammatory
      cytokine response and inducible NO synthase (iNOS). Dose-response studies
      revealed that pretreatment of mice with thearubigin (40 mg kg(-1) day(-1), i.g.
      for 10 days) significantly ameliorated the appearance of diarrhoea and the
      disruption of colonic architecture. Higher dose (100 mg kg(-1)) had comparable
      effects. This was associated with a significant reduction in the degree of both
      neutrophil infiltration and lipid peroxidation in the inflamed colon as well as
      decreased serine protease activity. Thearubigin also reduced the levels of NO and
      O(2)(-) associated with the favourable expression of T-helper 1 cytokines and
      iNOS. Consistent with these observations, nuclear factor kappa B (NF-kappa B)
      activation in colonic mucosa was suppressed in thearubigin-treated mice. The
      results of this study suggest that thearubigin, the most predominant polyphenol
      of black tea, exerts beneficial effects in experimental colitis and may,
      therefore, be useful in the treatment of inflammatory bowel disease.

PMID- 12787839
TI  - Evaluation of the effects of anti-pruritic drugs on scratch responses using
      histamine H1 receptor-deficient mice.
AB  - The effects of anti-pruritic drugs on scratching behavior associated with passive
      cutaneous anaphylaxis in histamine H(1) receptor-deficient and wild-type mice
      were studied. Passive sensitization with mouse monoclonal anti-dinitrophenyl
      immunoglobulin E (IgE) resulted in an increase in the incidence of scratching
      behavior induced by intravenous injection of dinitrophenyl-ovalbumin in both wild
      type and histamine H(1) receptor-deficient mice. The histamine H(1) receptor
      antagonist diphenhydramine inhibited scratching behavior induced by antigen in
      passively sensitized wild-type mice, whereas no effect was observed in histamine
      H(1) receptor-deficient mice. On the other hand, oxatomide inhibited scratching
      behavior in both mice, although the effect in wild-type mice was more potent than
      that in histamine H(1) receptor-deficient mice. Tranilast inhibited scratching
      behavior with the same potency in both mice. We concluded that the scratching
      behavior associated with passive cutaneous anaphylaxis involves not only
      histamine H(1) receptors but also other chemical mediators. Furthermore, the
      results of the present study indicated that oxatomide has an antagonistic effect
      on histamine H(1) receptors as well as anti-pruritic effect in vivo.

PMID- 12787840
TI  - A novel cholinesterase and brain-selective monoamine oxidase inhibitor for the
      treatment of dementia comorbid with depression and Parkinson's disease.
AB  - Degeneration of cholinergic cortical neurons is one of the main reasons for the
      cognitive deficit in dementia of the Alzheimer type (AD) and in dementia with
      Lewy bodies (DLB). Many subjects with AD and DLB have extrapyramidal dysfunction
      and depression resulting from degeneration of dopaminergic, noradrenergic and
      serotoninergic neurons. We prepared a novel drug, TV-3326 (N-propargyl-3R
      aminoindan-5yl)-ethyl methylcarbamate), with both cholinesterase (ChE) and
      monoamine oxidase (MAO) inhibitory activity, as potential treatment of AD and
      DLB. TV-3326 inhibits brain acetyl and butyrylcholinesterase (BuChE) in rats
      after oral doses of 10-100 mg/kg. After chronic but not acute treatment, it
      inhibits MAO-A and -B in the brain by more than 70% but has almost no effect on
      these enzymes in the small intestine in rats and rabbits. The brain selectivity
      results in minimal potentiation of the pressor response to oral tyramine. TV-3326
      acts like other antidepressants in the forced swim test in rats, indicating a
      potential for antidepressant activity. Chronic treatment of mice with TV-3326 (26
      mg/kg) prevents the destruction of nigrostriatal neurons by the neurotoxin MPTP
      (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). In addition to ChE and MAO
      inhibition, the propargylamine moiety of TV-3326 confers neuroprotective activity
      against cytotoxicity induced by ischemia and peroxynitrite in cultured neuronal
      cells that results from prevention of the fall in mitochondrial membrane
      potential and antiapoptotic activity. These unique multiple actions of TV-3326
      make it a potentially useful drug for the treatment of dementia with Parkinsonian
      like symptoms and depression.

PMID- 12787841
TI  - Drug craving and addiction: integrating psychological and
      neuropsychopharmacological approaches.
AB  - In the present review, an integrated approach to craving and addiction is
      discussed, which is based on recent insights from psychology and
      neuropsychopharmacology. An integrated model explains craving and relapse in
      humans by the psychological mechanism of "attentional bias" and provides
      neuropsychopharmacological mechanisms for this bias. According to this model,
      cognitive processes mediate between drug stimulus and the subject's response to
      this stimulus and subsequent behavioral response (e.g., drug use, relapse).
      According to the model, a conditioned drug stimulus produces an increase in
      dopamine levels in the corticostriatal circuit, in particular the anterior
      cingulate gyrus, amygdala, and nucleus accumbens, which in turn serves to draw
      the subject's attention towards a perceived drug stimulus. This process results
      in motor preparation and a hyperattentive state towards drug-related stimuli
      that, ultimately, promotes further craving and relapse. Evidence for this
      attentional bias hypothesis is reviewed from both the psychopharmacological and
      the neuroanatomical viewpoints. The attentional bias hypothesis raises several
      suggestions for clinical approaches and further research.

PMID- 12787842
TI  - A perspective on molecular genetic studies of tardive dyskinesia: one clue for
      individualized antipsychotic drug therapy.
AB  - Interindividual genetic profile differences related to antipsychotic drug therapy
      may be determined based on molecular genetic studies of the pathogenesis of
      schizophrenia and studies of antipsychotic drug responses (therapeutic as well as
      adverse responses). In the present article, we review molecular genetic studies
      of tardive dyskinesia (TD), which is a representative adverse response to
      antipsychotic drugs. Such studies have been performed to explore the gene
      associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs.
      Positive associations between several genes and TD have been reported. The
      accumulation of results from such studies will hopefully lead to individualized
      antipsychotic drug therapies that involve the application of new genomic
      techniques, including DNA microarrays. Subsequently, antipsychotic drugs may in
      the future be prescribed for smaller subgroups of patients who have been
      classified as having a particular genetic profile.

PMID- 12787843
TI  - Valproic acid fails to induce polycystic ovary syndrome in female rats.
AB  - PURPOSE: Valproic acid (VPA) treatment in female patients is suggested to be
      associated with the occurrence of a variety of endocrine side effects that
      include many characteristic symptoms of polycystic ovary syndrome (PCOS). The aim
      of our study was to prospectively measure whether VPA treatment was associated
      with the presentation of PCOS symptoms in rats, as well as determine whether this
      model could be used to examine the underlying mechanism by which these effects
      are induced. METHODS: Normal estrus-cycling female rats (n=22) were treated
      perorally three times daily with VPA (300 mg/kg/day), divalproex sodium (DVS)
      (330 mg/kg/day), or phosphate-buffered saline for a minimum of 30 days. PCOS
      associated symptoms (estrus cycle, weight, estradiol and testosterone levels,
      aromatase activity, and ovarian morphology) were assessed at baseline, mid-, and
      endpoint. RESULTS: There was no significant difference in the mean number of days
      animals were in proestrus-estrus or metestrus-diestrus between the three groups.
      All groups of animals gained weight during the study and there were no
      appreciable differences in mean weight gain or leptin between groups. Total serum
      estradiol or testosterone levels and ovarian aromatase activity were not
      significantly different between the groups. The number of corpora lutea was not
      significantly different between the groups; however, cystic follicles were
      present in 50% of the drug-treated animals compared to 25% of saline-treated
      animals. CONCLUSIONS: VPA and DVS treatment were associated with a higher
      proportion of animals developing cystic follicles but did not mimic the VPA
      induced PCOS that is observed in women. Thus, it appears that the rat has limited
      usefulness for modeling VPA-induced symptoms associated with PCOS.

PMID- 12787844
TI  - Influence of tiapride on platelet counts in healthy volunteers and patients with
      movement disorders.
AB  - BACKGROUND: The selective D2 antagonist tiapride is administered in various
      movement disorders. Furthermore, there are indications that tiapride increases
      platelet counts. AIM: To characterize tiapride's potential to increase platelet
      counts in healthy subjects and patients with movement disorders. METHODS: In Part
      A, 10 healthy volunteers received tiapride (300 mg/day) for 21 days in a
      longitudinal, prospective, open trial. One hundred healthy subjects served as
      controls. Part B was a retrospective analysis of 15 patients with movement
      disorders on tiapride [Huntington's disease (n=6), Morbus Little (n=3),
      hyperkinetic syndromes of undetermined etiology (n=3), blepharospasm (n=1),
      cervical dystonia (n=1), perioral dyskinesia (n=1)] and 15 age- and sex-matched
      controls. RESULTS: Part A: Although serum prolactin levels increased by 526+/
      14%, confirming good drug compliance, tiapride elicited only minor changes in
      platelet counts. Part B: Platelet counts correlated positively with the dose of
      tiapride (100-800 mg/day; r=.67; P=.007). Platelet counts were significantly
      higher in patients on tiapride compared to healthy age-matched controls (P<.001).
      Four patients responded to an increase in the tiapride dosage with an increase in
      platelet count by 97-173 cells/nl. CONCLUSION: Three weeks of treatment with
      tiapride (300 mg/day) is insufficient to elevate platelet counts to a clinically
      relevant extent in young healthy volunteers. However, in elderly patients with
      movement disorders tiapride treatment is associated with markedly increased
      platelet counts.

PMID- 12787845
TI  - Event-related potentials and neuropsychological tests in obsessive-compulsive
      disorder.
AB  - OBJECTIVE: Previous studies have provided evidence from event-related potentials
      (ERPs) and neuropsychological testing of abnormal cognitive processing in
      obsessive-compulsive disorder (OCD). The aim of this study was to further
      characterize the cognitive functions of the patients with OCD by utilizing ERPs
      and neuropsychological tests. METHODS: ERPs were recorded in a group of 31 drug
      free OCD patients without depression and 30 normal controls following verbal
      auditory stimuli using an oddball paradigm. The specific neuropsychological tests
      administered to assess cognitive functions in all participants were the Stroop
      Test, Trail Making Test, Design Fluency Test, Controlled Word Association Test
      (Verbal Fluency test). RESULTS: The patient group showed shorter P300 duration
      compared to normal controls. In neuropsychological tests, no significant
      differences were found between the two groups. Negative correlations between
      Stroop duration and P300 amplitudes in occipital, parietal, and temporal anterior
      regions were observed. CONCLUSION: Shorter P300 duration may indicate an
      acceleration in the P300 process, and speeding of cognitive processing,
      dysfunction of cortico-subcortical circuits, or some combination of all of the
      above.

PMID- 12787846
TI  - Complications of a trophic xenotransplant approach in parkinsonian monkeys.
AB  - Various restorative cell transplantation strategies have been investigated to
      substitute for lost dopamine (DA) neurons or to enhance DA synthesis in
      Parkinson's disease. Intracerebral implantation of engineered cells encapsulated
      in a semipermeable polymer membrane constitutes one way to deliver bioactive
      substances unable to cross the blood-brain barrier while avoiding the need for
      long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF)
      has shown trophic effects on DA neurons but effective and sustained delivery
      within the brain parenchyma remains problematic. The long-term efficacy and late
      complications of a xenotransplant approach utilizing GDNF-expressing encapsulated
      baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned
      parkinsonian cynomolgus monkeys received five devices containing active or inert
      cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart
      and animals were sacrificed 4 months later for analyses. No definite motor
      benefit was observed, DA levels were comparable between GDNF- and control cell
      implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the
      substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis
      in the explanted devices were negligible. The brain tissue surrounding all
      implants showed an intense immune reaction with prominent "foreign body"
      inflammatory infiltrates. Membrane biophysics, the cell type used, and the
      extended period of time the devices remained in situ may have contributed to the
      negative outcome and should be addressed in future investigations using this
      approach.

PMID- 12787847
TI  - Effects of TNF-alpha injected intracisternally on the nociceptive jaw-opening
      reflex and orofacial formalin test in freely moving rats.
AB  - The present study was performed to investigate the effects of central cytokines
      on the modulation of nociception in the orofacial area. A nociceptive jaw-opening
      reflex (JOR) and an orofacial formalin test were monitored after intracisternal
      administration of tumor necrosis factor (TNF)-alpha in freely moving rats.
      Experiments were carried out on 83 male rats weighing 300-350 g and surgical
      procedures were performed under pentobarbital sodium. After intracisternal
      injection of Tnf-alpha, digastric electromyogram (dEMG) and noxious behavioral
      responses were monitored. In the nociceptive JOR, dEMG was not significantly
      changed after intracisternal injection of 200 pg and 2 ng Tnf-alpha. However, 20
      ng Tnf-alpha suppressed dEMG to 72+/-6% of the control values. The orofacial
      formalin responses showed two distinct phases separated by a time of relative
      inactivity with an early short-lasting response (0-9 min, first phase) and a
      continuous prolonged response (10-45 min, second phase). In the inflammatory
      orofacial formalin test, intracisternal injection of 20 pg Tnf-alpha did not
      change the number of noxious behavioral responses produced by formalin injection.
      However, 200 pg Tnf-alpha injected intracisternally significantly increased the
      number of noxious behavioral responses produced by formalin injection in both the
      early and late phases, and 2 ng Tnf-alpha increased formalin induced noxious
      behavioral responses in only the late phase. A higher dose of 20 ng Tnf-alpha did
      not change the number of noxious behavioral responses produced by formalin
      injection. The hyperalgesic action of Tnf-alpha injected intracisternally was
      blocked by pretreatment with the interleukin-1 (IL-1) receptor antagonist. These
      results suggest that central Tnf-alpha modulates the transmission of nociceptive
      information in the orofacial area. However, the hypo/hyperalgesic response of
      central Tnf-alpha seems to depend on the orofacial pain model or in a dose
      related manner. The hyperalgesic response of central Tnf-alpha seems to be
      mediated by the IL-1 receptor.

PMID- 12787848
TI  - Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder.
AB  - The aim of the present study was to investigate the effect of adjunctive
      olanzapine in patients with obsessive-compulsive disorder (OCD) refractory to
      paroxetine. Twenty-one patients unresponsive to treatment with paroxetine,
      administered for at least 12 weeks at the dose of 60 mg/day, participated to a 12
      week open-label, add-on trial with olanzapine (10 mg/day). The psychopathological
      state was evaluated by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and by
      Clinical Global Impression (CGI). Three patients did not complete the 12-week
      adjunctive treatment with olanzapine. In the 18 completers, the mean Y-BOCS score
      decreased significantly from 27.1+/-4.0 at baseline to 20.1+/-3.9 at final
      evaluation (P<.001). Seven patients (38.9%) were rated as responders at final
      evaluation. Steady-state plasma concentrations of paroxetine were not modified
      during olanzapine coadministration. The drug combination was generally well
      tolerated and initial sedation and weight gain were the most frequent unwanted
      effects. Our findings confirm the results of previous studies and indicate that
      the addition of olanzapine to ongoing treatment with serotonin reuptake
      inhibitors (SRI) may be beneficial in some patients unresponsive to SRI
      monotherapy.

PMID- 12787849
TI  - Effects of the selective nonpeptide corticotropin-releasing factor receptor 1
      antagonist antalarmin in the chronic mild stress model of depression in mice.
AB  - Several recent studies on corticotropin-releasing factor (CRF) have suggested
      that this neuropeptide may play a role in depression. Consequently, CRF receptor
      antagonists have been proposed as potential new agents for the treatment of this
      condition. This study investigated the effects of a 4-week treatment with the
      well-known CRF(1) receptor antagonist, antalarmin, and the prototypical selective
      serotonin reuptake inhibitor (SSRI), fluoxetine, in the chronic mild stress (CMS)
      model in BALB/c mice. Animals were exposed to 9 weeks of CMS which rapidly
      (within 2 weeks) produced decrease of physical state (PS), body weight gain and
      blunted emotional response in the light/dark test. Chronic treatment with
      antalarmin (10 mg/kg ip) and fluoxetine (10 mg/kg ip) led to an improvement of
      CMS-induced modifications. These results suggest that CRF(1) receptor antagonists
      may represent potential antidepressants.

PMID- 12787850
TI  - Duration of transcranial magnetic stimulation effects on the neuroendocrine
      stress response and coping behavior of adult male rats.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is a relatively novel,
      noninvasive method of altering cerebral electrophysiological activity that
      produces localized and reversible changes in brain tissue. TMS has been shown to
      have antidepressant properties in both human trials and animal models.
      Additionally, TMS may alter hypothalamic-pituitary-adrenal (HPA) function
      resulting in a normalized dexamethasone suppression test in some depressed
      subjects and an attenuated stress-induced increase in adrenocorticotropic hormone
      (ACTH) and a possibly lowered basal corticosterone (CORT) concentration in rats.
      This research was undertaken to investigate the duration of these behavioral and
      neuroendocrine effects of TMS in rats. METHODS: In this study, serum ACTH, CORT,
      testosterone, and luteinizing hormone (LH) concentrations following and
      immobility parameters during a forced-swim test in adult male rats were evaluated
      immediately and 1, 3, 5, 7, and 14 days subsequent to a 10-day course of once
      daily TMS or sham application. RESULTS: TMS animals had significantly higher ACTH
      and CORT concentrations immediately following the 10-day course of TMS compared
      to sham controls. Higher CORT concentrations (numerically but not statistically)
      were displayed by TMS-treated animals 1 and 3 days after the 10-day application
      course, although there were no significant differences between TMS and sham
      groups for ACTH or CORT levels 1, 3, 5, 7, and 14 days following application of
      sham or TMS. No significant differences were found between groups for serum
      testosterone and LH levels at any given collection time point. Immobility time, a
      measure of coping ability that is predictive of human antidepressant response,
      was significantly decreased (i.e., time spent actively swimming was significantly
      increased) immediately after the 10-day course of TMS. Thereafter, a
      nonsignificant numerical trend at 1 and 3 days after TMS application for
      immobility times between the TMS and control groups was observed (TMS<control
      values). No significant differences in immobility between TMS and control animals
      were found at subsequent time points. CONCLUSIONS: The present findings suggest
      that the HPA stress axis is significantly altered immediately following a 10-day
      course of TMS in that a significant increase in ACTH and CORT levels in TMS
      treated animals corresponded to a significant decrease in immobility times in the
      forced-swim test compared to control values. Finally, based upon the obtained
      results, the TMS effects in rats appear to be of relatively short duration.

PMID- 12787851
TI  - Fluoxetine decreases stereotypic behavior in primates.
AB  - BACKGROUND: Primates reared in captivity may display stereotypic behaviors. These
      behaviors are arguably reminiscent of human obsessive-compulsive or posttraumatic
      symptoms, which respond to selective serotonin reuptake inhibitors (SSRIs).
      Captive primates with marked stereotypic behaviors were entered into a randomized
      controlled study of the SSRI, fluoxetine. METHODS: A sample of 10 vervet monkeys
      with behaviors such as marked saluting, somersaulting, weaving, or head tossing
      was selected. Subjects were randomized to receive fluoxetine 1 mg/kg for 6 weeks
      (n=5) or no treatment (n=5). A rater blind to the medication status of subjects
      noted the frequency of the stereotypic behaviors. RESULTS: Repeated-measures
      analysis of variance (RM-ANOVA) demonstrated a significant GroupxTime difference
      with significantly fewer stereotypic symptoms in the fluoxetine group by
      endpoint. At this time, three of the five fluoxetine-treated subjects (but none
      of the no-treatment subjects) were responders on the Clinical Global Impressions
      (CGI) change item (CGI < or =2). CONCLUSIONS: Stereotypic behaviors in captive
      vervets gradually and partially decrease in response to administration of an
      SSRI, paralleling research on human anxiety symptoms. Further research on animal
      stereotypies may be useful in providing appropriate veterinary care, and in
      exploring the underlying neurobiology of certain psychiatric disorders.

PMID- 12787852
TI  - Enhancement of serotonin-1A receptor dependent responses following withdrawal of
      haloperidol in rats.
AB  - Although haloperidol is widely prescribed for the treatment of schizophrenia, its
      beneficial effects are accompanied by extrapyramidal side effects (EPS). In view
      of a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the
      elicitation of EPS, the present study concerns pre- and postsynaptic responses to
      a selective 5-HT-1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8
      OH-DPAT) following acute and chronic administration of haloperidol in rats. In
      the acute administration study, effects of 8-OH-DPAT (0.5 mg/kg) were monitored
      30 min after single injection of haloperidol (5 mg/kg). In the chronic
      administration study, effects of 8-OH-DPAT (0.5 mg/kg) were monitored 48 h after
      withdrawal from repeated (two times a day for 2 weeks) administration of
      haloperidol (5 mg/kg). The intensity of 5-HT syndrome elicited by 8-OH-DPAT was
      taken as measure of postsynaptic response. 8-OH-DPAT-induced decreases of 5-HT
      synthesis were taken as measure of presynaptic response. Results showed that 8-OH
      DPAT-induced locomotion was smaller in acute haloperidol-treated rats.
      Conversely, these effects of 8-OH-DPAT were greater in chronic haloperidol
      treated rats. Animals injected acutely or chronically with haloperidol exhibited
      greater 5-HT synthesis in the striatum. Administration of 8-OH-DPAT did not
      decrease 5-HT synthesis in the striatum of acute haloperidol-treated rats but
      decreased it in the striatum of chronic haloperidol-treated rats. The results
      show an increase in the effectiveness of pre- and postsynaptic 5-HT-1A receptor
      dependent responses following chronic administration of haloperidol. A causal
      role of 5-HT-1A receptor responsiveness in the greater incidences of EPS in
      patients treated with typical neuroleptics such as haloperidol is discussed.

PMID- 12787853
TI  - Acamprosate does not induce a conditioned place preference and reveals no state
      dependent effects in this paradigm.
AB  - To evaluate the putative rewarding properties of the anticraving substance
      acamprosate, male rats learned to associate injections of vehicle and acamprosate
      (200 mg/kg ip) with two visually contrasting compartments in a place conditioning
      paradigm. The degree of preference for the acamprosate-associated compartment was
      determined, in both a postconditioning test with undrugged animals and a
      consecutive test with drugged animals, to rule out the possibility that a
      putatively rewarding effect of acamprosate may have been masked by state
      dependent effects. The animals did not show any preference for the substance
      paired compartment, neither in the undrugged nor in the drugged state. In
      conclusion, acamprosate has no rewarding properties as shown in place preference.
      Therefore, it may prevent a relapse in detoxified alcoholics in a way other than
      by simply substituting the rewarding effects of ethanol. This adds to the
      therapeutic value of acamprosate in the treatment of drug craving.

PMID- 12787854
TI  - Neuropsychological performance and regional cerebral blood flow in obsessive
      compulsive disorder.
AB  - Convergent findings from neuropsychological and neuroimaging studies have
      suggested that neural dysfunction in frontal-subcortical circuits may play a
      central role in the pathophysiology of obsessive-compulsive disorder (OCD). To
      further examine the relationship between these two sets of findings we
      investigated both neuropsychological functions and regional cerebral blood flow
      (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV
      criteria for OCD and 14 healthy controls matched for age, gender, handedness, and
      education were assessed on neuropsychological tests that included Trail Making
      Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency
      Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with 99 mTc
      hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed
      tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF
      (copy), VFT, and WCST (perseverative errors). Spearman's correlations indicated
      that severity of OCD correlated inversely with performance on the RCF (copy and
      recall scores) and positively with rCBF in the right thalamus. Positive
      correlations were observed between nonperseverative errors (WCST) and rCBF in
      frontal areas and anterior cingulate. Perseverative errors (WCST) correlated
      negatively with rCBF in the right thalamus. These findings are consistent with
      most previously published studies and suggest neural dysfunctions in the frontal
      subcortical circuits probably more pronounced in the right hemisphere. They also
      extend the existing research, showing associations between deficits in cortical
      subcortical circuitry and performance on neuropsychological tests of controlled
      attention and visuospatial functions.

PMID- 12787855
TI  - Safety, effectiveness, and quality of life of olanzapine in first-episode
      schizophrenia: a naturalistic study.
AB  - OBJECTIVE: This study evaluated the effectiveness, safety, and quality of life
      (Qol) offered by olanzapine in first-episode schizophrenia. METHOD: One hundred
      and eighty-two patients with first-episode schizophrenia (ICD-10) drawn from a
      larger, naturalistic, study were evaluated after 6 months of treatment with
      olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was
      assessed using the Clinical Global Impression-Severity (CGI-S) and Global
      Assessment of Function (GAF). AWAD and EuroQol scales were used to evaluate
      patients' attitude towards medication and Qol, respectively. RESULTS: Subjects
      treated with olanzapine, risperidone, and CA showed similar improvements on CGI-S
      and GAF. Treatment-emergent, extrapyramidal symptoms were significantly lower in
      olanzapine-treated patients (17.8%) than in the risperidone (46.4%) and CA
      (62.2%) groups. Compared to CA, olanzapine and risperidone showed significantly
      greater improvement on the visual analog scale of EuroQol. Olanzapine-treated
      patients also showed significantly improved AWAD scores. CONCLUSIONS: In first
      episode schizophrenia, atypical antipsychotics were effective, and improved Qol.
      Olanzapine had a lower incidence of extrapyramidal symptoms and better subjective
      acceptance of medication.

PMID- 12787856
TI  - Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of
      patients with schizophrenia.
AB  - Basing primarily on the facts of altered levels of glutamate neurotransmitter,
      its receptors and transporters in schizophrenic brain, the "glutamatergic
      hypothesis" of schizophrenia has been broadened into the field of brain glutamate
      metabolism. Significantly changed levels of glutamine synthetase (GS) and
      glutamate dehydrogenase (GDH), the key enzymes involved in glutamine-glutamate
      cycling between neurons and glia, have been found in the prefrontal cortex (area
      10) of patients with schizophrenia compared to controls (P<.01). The data were
      obtained by enzymatic activity determinations as well as immunoreactivity level
      evaluations for GS, glutamine synthetase-like protein (GSLP), and three GDH
      isoenzymes in brain extracts by immunoblotting using specific polyclonal and
      monoclonal antibodies. Inverse changes in amounts of proteins of GS and GSLP, as
      well as elevation in amounts of GDH isoenzymes have been observed in
      schizophrenia. The presented results provide evidence for the impairment of
      glutamate metabolism and, in turn, abnormalities in functioning of the glutamate
      glutamine cycle in the frontal cortex of patients with schizophrenia.

PMID- 12787857
TI  - Open-label nefazodone in patients with a major depressive episode and alcohol
      dependence.
AB  - PURPOSE: Major depressive disorder (MDD) and alcohol dependence (AD) frequently
      occur together. However, MDD clinical trials generally exclude patients with
      alcohol-related disorders. GENERAL METHODS: A 12-week, open-label trial of
      nefazodone in a group of people (n=13) with both a current major depressive
      episode and current AD was conducted to examine the effect of this antidepressant
      on depressive symptoms, alcohol use, and cognition. FINDINGS: Scores on the
      Hamilton Rating Scale for Depression (HRSD) and Hamilton Rating Scale for Anxiety
      (HRSA) significantly decreased from baseline to exit. In addition, significant
      reduction in alcohol craving, drinks/week, and days of alcohol use/week was
      found. Scores on the Rey Auditory Verbal Learning Test (RAVLT) did not
      significantly improve during the study. Changes in mood/anxiety and memory did
      not correlate with changes in alcohol use. CONCLUSIONS: Thus, nefazodone therapy
      was associated with improvement in mood/anxiety and alcohol use, which seem to be
      independent of each other in this patient sample. However, declarative memory,
      which was low average at baseline, did not show statistically significant
      improvement during the 12 weeks of the study.

PMID- 12787858
TI  - Ketamine-induced changes in rat behaviour: A possible animal model of
      schizophrenia.
AB  - It was investigated whether subchronic application of 30 mg/kg ketamine (Ket)
      induces reliable changes in behaviour and parameters of dopaminergic,
      glutamatergic, and serotonergic neurotransmissions, which might be the basis of
      an animal model in schizophrenia research. To test this, rats were injected with
      30 mg/kg ip Ket daily for five consecutive days. In response to the first Ket
      injection, there was a decrease in activity time representing an acute Ket
      effect. Following the fifth injection, there were no differences between Ket- and
      saline (sal)-injected control rats in activity time, which might be a tolerance
      reaction. The following experiments were performed 2 or 4 weeks after Ket
      treatment. There were no effects on anxiety in either vehicle or Ket-treated rats
      using either low or high illumination levels in the elevated plus-maze. In the
      social interaction test, both groups of rats spent comparable times in social
      contact. The percentage of nonaggressive behaviour was decreased in Ket-treated
      rats. Two weeks after completion of the treatment, there was no effect on
      prepulse inhibition (PPI). Four weeks after the final Ket injection, latent
      inhibition (LI) was disrupted. There was no difference in the animals' activity
      in reaction to apomorphine (Apo) administration. Ket-treated rats injected with
      0.1 mg/kg MK-801 showed an enhancement in locomotor activity. Ket treatment leads
      to an increase in D2 receptor binding in the hippocampus and a decrease in
      glutamate receptor binding in the frontal cortex. The authors did not find any
      changes in D1 receptor binding. The density of dopamine transporters was
      increased in the striatum. The density of 5-HT transporters was increased in the
      striatum, the hippocampus, and the frontal cortex. The results suggest that
      subchronic treatment with subanaesthetic doses of Ket induce schizophrenia
      related alterations, which might be a useful animal model in the study of this
      disease.

PMID- 12787859
TI  - Influence of hypoosmolality on the blood-brain barrier permeability during
      epileptic seizures.
AB  - Changes in the blood-brain barrier permeability to macromolecules were
      investigated during pentylenetetrazol-induced seizures, using Evans-blue as an
      indicator, in water-intoxicated and nonintoxicated Wistar albino (210-250 g)
      adult rats of both sexes. Evans-blue albumin extravasation was judged visually
      and estimated quantitatively with a spectrophotometer using homogenized brain to
      release the dye. Hypoosmolar treatment (water intoxication) was performed by the
      intraperitoneal administration of distilled water to a volume of 10% of the body
      weight; Six groups of rats were studied. Group I: female control (n=10), Group
      II: male control (n=10), Group III: nonwater-intoxicated female+seizure (n=15),
      Group IV: nonwater-intoxicated male+seizure (n=15), Group V: water-intoxicated
      female+seizure (n=15), Group VI: water-intoxicated male+seizure (n=15).
      Approximately 2 h after the injection of water, the plasma osmolarity had
      decreased by 25-30 mosm. Our results revealed that in female rats, the
      extravasation of Evans-blue albumin was greater in the brains of water
      intoxicated rats compared to nonwater-intoxicated rats after pentylenetetrazol
      induced seizures. In addition, hypoosmotic female rats were shown to have a
      larger increase in blood-brain barrier permeability than hypoosmotic male rats
      after pentylenetetrazol-induced seizures. This difference between male and female
      rats was found to be significant (P=.005).

PMID- 12787861
TI  - Dietary cytidine (5')-diphosphocholine supplementation protects against
      development of memory deficits in aging rats.
AB  - The present study was designed to assess the effect of supplementation with
      dietary cytidine (5')-diphosphocholine (CDP-choline), a source of cytidine and
      choline, on memory in young and older rats. Although the hippocampal-dependent
      memory deficits in aged rats are well documented, cognitive functioning in early
      aging has not been as thoroughly evaluated. Female Sprague-Dawley rats (3 or 15
      months of age) consumed either a control diet or a diet supplemented with CDP
      choline (approximately 500 mg/kg/day) for 8 weeks, after which they were trained
      to perform spatial and cued versions of the Morris water maze. Compared with
      young rats, aged rats exhibited a selective deficit in spatial memory tasks that
      required rats to retain information for 24 h or longer. CDP-choline
      supplementation protected against the development of this deficit, but had no
      memory-enhancing effect in normal young rats. These findings suggest that early
      aged rats display a selective impairment in hippocampal-dependent long-term
      memory, and that dietary CDP-choline supplementation can protect against this
      deficit.

PMID- 12787860
TI  - Depression in premenopausal women: gonadal hormones and serotonergic system
      assessed by D-fenfluramine challenge test.
AB  - PURPOSE: The aim of the study was to compare the activity of gonadal hormones and
      serotonergic system in premenopausal women with or without depression in relation
      to clinical and hormonal indices of menopause. METHODS: The sample included 60
      women with single or recurrent major depressive episode with disease onset after
      38 year of age (mean age 43 years) and 30 healthy control women (mean age 41
      years). Psychometric assessment was done by means of 17-item Hamilton Depression
      Rating Scale (HDRS) and the Beck Depression Inventory (BDI). The presence of
      menopausal symptoms was assessed by Kupperman Menopause Index (KMI). Activity of
      gonadal axis was measured by estimating estradiol and follicle-stimulating
      hormone (FSH) levels. For the assessment of central serotonergic activity, the D
      fenfluramine test was used. RESULTS: Depressed women had higher intensity of
      menopausal symptoms, significantly lower concentration of estradiol, and higher
      of FSH than control women. Severity of depression correlated with both the
      intensity of menopausal symptoms and the concentration of FSH. Baseline levels of
      prolactin were not different in both groups. Following D-fenfluramine
      administration, there was a significant increase in prolactin concentration in
      healthy women and a transient decrease in depressed ones. Baseline cortisol level
      was significantly higher in depressed women and correlated with the severity of
      depression. D-Fenfluramine challenge caused a significant increase of cortisol
      secretion in healthy women and a significant decrease in depressed ones. A
      relationship was observed between baseline estradiol, FSH, and cortisol level and
      the magnitude of prolactin and cortisol response to D-fenfluramine. CONCLUSIONS:
      In premenopausal women, a high degree of interconnections was demonstrated
      between symptoms of depression and symptoms of menopause on both clinical and
      hormonal level. The results confirm the association between depressive and
      menopausal symptoms as well as an involvement of gonadal hormones, cortisol, and
      serotonin deficiency in this process.

PMID- 12787862
TI  - Bromocriptine augmentation therapy in a patient with Cotard's syndrome.
AB  - A 72-year-old female with bipolar I disorder developed Cotard's syndrome, i.e.,
      various delusions of negation accompanied by severe depressive symptoms. She
      responded neither to the combination of antipsychotic drug and antidepressant nor
      to the lithium augmentation therapy. However, the delusions and depressive
      symptoms improved dramatically after the addition of bromocriptine 2.5-5 mg/day
      to the combination of clomipramine and lithium. This report suggests that
      bromocriptine augmentation therapy might be effective at least for some patients
      with Cotard's syndrome in mood disorders.

PMID- 12787864
TI  - Structure and innervation of the cochlea.
AB  - The role of the cochlea is to transduce complex sound waves into electrical
      neural activity in the auditory nerve. Hair cells of the organ of Corti are the
      sensory cells of hearing. The inner hair cells perform the transduction and
      initiate the depolarization of the spiral ganglion neurons. The outer hair cells
      are accessory sensory cells that enhance the sensitivity and selectivity of the
      cochlea. Neural feedback loops that bring efferent signals to the outer hair
      cells assist in sharpening and amplifying the signals. The stria vascularis
      generates the endocochlear potential and maintains the ionic composition of the
      endolymph, the fluid in which the apical surface of the hair cells is bathed. The
      mechanical characteristics of the basilar membrane and its related structures
      further enhance the frequency selectivity of the auditory transduction mechanism.
      The tectorial membrane is an extracellular matrix, which provides mass loading on
      top of the organ of Corti, facilitating deflection of the stereocilia. This
      review deals with the structure of the normal mature mammalian cochlea and
      includes recent data on the molecular organization of the main cell types within
      the cochlea.

PMID- 12787866
TI  - Primary innervation of the avian and mammalian cochlear nucleus.
AB  - The auditory nerve of birds and mammals exhibits differences and similarities,
      but given the millions of years since the two classes diverged from a common
      ancestor, the similarities are much more impressive than the differences. The
      avian nerve is simpler than that of mammals, but share many fundamental features
      including principles of development, structure, and physiological properties.
      Moreover, the available evidence shows that the human auditory nerve follows this
      same general organizational plan. Equally impressive are reports that homologous
      genes in worms, flies, and mice exert the same heredity influences in man. The
      clear implication is that animal studies will produce knowledge that has a direct
      bearing on the human condition.

PMID- 12787865
TI  - Development of inner ear afferent connections: forming primary neurons and
      connecting them to the developing sensory epithelia.
AB  - The molecular and cellular origin of the primary neurons of the inner ear, the
      vestibular and spiral neurons, is reviewed including how they connect to the
      specific sensory epithelia and what the molecular nature of their survival is.
      Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH)
      protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is
      the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1
      results in absence of primary neuron formation; targeted null mutation of NeuroD
      results in loss of almost all spiral and many vestibular neurons. NeuroD and a
      later expressed gene, Brn3a, play a role in pathfinding to and within sensory
      epithelia. The molecular nature of this pathfinding property is unknown.
      Reduction of hair cells in ngn1 null mutations suggests a clonal relationship
      with primary neurons. This relationship may play some role in specifying the
      identity of hair cells and the primary neurons that connect with them. Primary
      neuron neurites growth to sensory epithelia is initially independent of trophic
      factors released from developing sensory epithelia, but becomes rapidly dependent
      on those factors. Null mutations of specific neurotrophic factors lose distinct
      primary neuron populations which undergo rapid embryonic cell death.

PMID- 12787867
TI  - Parallel auditory pathways: projection patterns of the different neuronal
      populations in the dorsal and ventral cochlear nuclei.
AB  - The cochlear nuclear complex gives rise to widespread projections to nuclei
      throughout the brainstem. The projections arise from separate, well-defined
      populations of cells. None of the cell populations in the cochlear nucleus
      projects to all brainstem targets, and none of the targets receives inputs from
      all cell types. The projections of nine distinguishable cell types in the
      cochlear nucleus-seven in the ventral cochlear nucleus and two in the dorsal
      cochlear nucleus-are described in this review. Globular bushy cells and two types
      of spherical bushy cells project to nuclei in the superior olivary complex that
      play roles in sound localization based on binaural cues. Octopus cells convey
      precisely timed information to nuclei in the superior olivary complex and lateral
      lemniscus that, in turn, send inhibitory input to the inferior colliculus.
      Cochlear root neurons send widespread projections to areas of the reticular
      formation involved in startle reflexes and autonomic functions. Type I multipolar
      cells may encode complex features of natural stimuli and send excitatory
      projections directly to the inferior colliculus. Type II multipolar cells send
      inhibitory projections to the contralateral cochlear nuclei. Fusiform cells in
      the dorsal cochlear nucleus appear to be important for the localization of sounds
      based on spectral cues and send direct excitatory projections to the inferior
      colliculus. Giant cells in the dorsal cochlear nucleus also project directly to
      the inferior colliculus; some of them may convey inhibitory inputs to the
      contralateral cochlear nucleus as well.

PMID- 12787868
TI  - Central projections of the vestibular nerve: a review and single fiber study in
      the Mongolian gerbil.
AB  - The primary purpose of this article is to review the anatomy of central
      projections of the vestibular nerve in amniotes. We also report primary data
      regarding the central projections of individual horseradish peroxidase (HRP)
      filled afferents innervating the saccular macula, horizontal semicircular canal
      ampulla, and anterior semicircular canal ampulla of the gerbil. In total, 52
      characterized primary vestibular afferent axons were intraaxonally injected with
      HRP and traced centrally to terminations. Lateral and anterior canal afferents
      projected most heavily to the medial and superior vestibular nuclei. Saccular
      afferents projected strongly to the spinal vestibular nucleus, weakly to other
      vestibular nuclei, to the interstitial nucleus of the eighth nerve, the cochlear
      nuclei, the external cuneate nucleus, and nucleus y. The current findings
      reinforce the preponderance of literature. The central distribution of vestibular
      afferents is not homogeneous. We review the distribution of primary afferent
      terminations described for a variety of mammalian and avian species. The
      tremendous overlap of the distributions of terminals from the specific vestibular
      nerve branches with one another and with other sensory inputs provides a rich
      environment for sensory integration.

PMID- 12787870
TI  - Central vestibular system: vestibular nuclei and posterior cerebellum.
AB  - The vestibular nuclei and posterior cerebellum are the destination of vestibular
      primary afferents and the subject of this review. The vestibular nuclei include
      four major nuclei (medial, descending, superior and lateral). In addition,
      smaller vestibular nuclei include: Y-group, parasolitary nucleus, and nucleus
      intercalatus. Each of the major nuclei can be subdivided further based primarily
      on cytological and immunohistochemical histological criteria or differences in
      afferent and/or efferent projections. The primary afferent projections of
      vestibular end organs are distributed to several ipsilateral vestibular nuclei.
      Vestibular nuclei communicate bilaterally through a commissural system that is
      predominantly inhibitory. Secondary vestibular neurons also receive convergent
      sensory information from optokinetic circuitry, central visual system and neck
      proprioceptive systems. Secondary vestibular neurons cannot distinguish between
      sources of afferent activity. However, the discharge of secondary vestibular
      neurons can distinguish between "active" and "passive" movements. The posterior
      cerebellum has extensive afferent and efferent connections with vestibular
      nuclei. Vestibular primary afferents are distributed to the ipsilateral uvula
      nodulus as mossy fibers. Vestibular secondary afferents are distributed
      bilaterally. Climbing fibers to the cerebellum originate from two subnuclei of
      the contralateral inferior olive; the dorsomedial cell column and beta-nucleus.
      Vestibular climbing fibers carry information only from the vertical semicircular
      canals and otoliths. They establish a coordinate map, arrayed in sagittal zones
      on the surface of the uvula-nodulus. Purkinje cells respond to vestibular
      stimulation with antiphasic modulation of climbing fiber responses (CFRs) and
      simple spikes (SSs). The modulation of SSs is out of phase with the modulation of
      vestibular primary afferents. Modulation of SSs persists, even after vestibular
      primary afferents are destroyed by a unilateral labyrinthectomy, suggesting that
      an interneuronal network, triggered by CFRs is responsible for SS modulation. The
      vestibulo-cerebellum, imposes a vestibular coordinate system on postural
      responses and permits adaptive guidance of movement.

PMID- 12787871
TI  - Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator
      and neuroprotector.
AB  - Uncoupling proteins (UCPs) are localized in the inner membrane of the
      mitochondria in diverse tissues and decrease mitochondrial membrane potential.
      The first of these proteins, UCP1, was discovered in brown adipose tissue, where
      it has a well-described role in thermogenesis. The functional significance of
      other UCPs, including UCP2, is less well understood. Here we summarize the recent
      advancements on the role of UCP2 in the brain and portray this uncoupler as an
      important player in normal neuronal function as well as a key cell death
      suppressing device. These previously unknown functions of UCPs offer new avenues
      not only for the better understanding of these proteins but also for the
      furthering of our knowledge on the central nervous system in healthy and disease
      states.

PMID- 12787869
TI  - Development of vestibular afferent projections into the hindbrain and their
      central targets.
AB  - In contrast to most other sensory systems, hardly anything is known about the
      neuroanatomical development of central projections of primary vestibular neurons
      and how their second order target neurons develop. Recent data suggest that
      afferent projections may develop not unlike other sensory systems, forming first
      the overall projection by molecular means followed by an as yet unspecified phase
      of activity mediated refinement. The latter aspect has not been tested critically
      and most molecules that guide the initial projection are unknown. The molecular
      and topological origin of the vestibular and cochlear nucleus neurons is also
      only partially understood. Auditory and vestibular nuclei form from several
      rhombomeres and a given rhombomere can contribute to two or more auditory or
      vestibular nuclei. Rhombomere compartments develop as functional subdivisions
      from a single column that extends from the hindbrain to the spinal cord.
      Suggestions are provided for the molecular origin of these columns but data on
      specific mutants testing these proposals are not yet available. Overall, the
      functional significance of both overlapping and segregated projections are not
      yet fully experimentally explored in mammals. Such lack of details of the adult
      organization compromises future developmental analysis.

PMID- 12787872
TI  - Characterization of maleimide-activated Ca2+ entry in neutrophils.
AB  - N-Ethylmaleimide (NEM), a thio-alkylating agent, concentration-dependently
      stimulated the elevation of [Ca(2+)](i) in rat neutrophils in the presence of
      external Ca(2+). This effect was not observed in Ca(2+)-free medium and was
      abrogated by dithiothreitol pretreatment. The application of NEM after
      cyclopiazonic acid (CPA) stimulated the store-emptying activation of Ca(2+)
      entry. Unlike CPA-induced cation entry, NEM showed poor uptake of Ba(2+) and
      Sr(2+) and did not induce Mn(2+) influx. NEM diminished CPA-induced Mn(2+)
      influx, an effect that was blocked by dithiothreitol. Both Ni(2+) and La(3+)
      attenuated the elevation of [Ca(2+)](i) in response to NEM; however, greater
      resistance was observed to Ni(2+) inhibition of NEM-induced Ca(2+) influx than
      inhibition of store-operated Ca(2+) entry. Both cis-N-(2
      phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12,330A) and 1-[beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), Ca(2+)
      channel blockers, and calyculin A, an inhibitor of protein serine/threonine
      phosphatases 1/2, diminished the NEM-induced Ca(2+) entry. Treatment of cells
      with genistein, a general tyrosine kinase inhibitor, or with wortmannin and 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), phosphatidylinositol 3
      kinase inhibitors, had no appreciable inhibitory effects on the action of NEM.
      However, 2-aminoethyldiphenyl borate, an inositol trisphosphate receptor
      antagonist, enhanced rather than inhibited the [Ca(2+)](i) change in response to
      NEM. These results indicate that NEM stimulates Ca(2+) entry and regulates Ca(2+)
      signaling through direct thiol oxidation, bypassing the cellular signal
      transduction pathway. The NEM-regulated Ca(2+) signal demonstrates
      characteristics that distinguish it from the store-emptying operation in
      neutrophils, and therefore represents two distinct modes of Ca(2+) regulation.

PMID- 12787873
TI  - Expression of the murine CB2 cannabinoid receptor using a recombinant Semliki
      Forest virus.
AB  - A recombinant Semliki Forest virus (SFV) RNA construct, SFV1-mCB(2) RNA, was
      employed for the high-level expression of the murine CB(2) (mCB(2)) cannabinoid
      receptor in baby hamster kidney cells. Biosynthetic radiolabel incorporation
      studies in concert with urea-sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (urea-SDS-PAGE) and western immunoblotting revealed that two
      major proteins of approximately 26 and 40kDa were produced by the construct. The
      40kDa product, but not the 26kDa product, was glycosylated as determined by 2
      deoxy-D-glucose incorporation and peptide-N-glycosidase F digestion analysis.
      Assessment of [3H]CP55940 ([3H]-(-)-cis-3-[2-hydroxy-4-(1,1
      dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) binding data for
      membranes of cells transfected with SFV1-mCB(2) RNA indicated a K(d) of 0.35+/
      0.04nM and a B(max) of 24.4+/-2.7pmol/mg. A rank order of binding affinities for
      cannabinoids, which paralleled that reported for native mCB(2) receptors, was
      observed. The CB(2) receptor-specific antagonist SR144528 (N-[(1S)-endo-1,3,3
      trimethyl bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4
      methylbenzyl)-pyrazole-3-carboxamide) blocked binding of [3H]CP55940, while the
      CB(1) receptor-specific antagonist SR141716A [N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride] had a minimal effect. These results indicate that the recombinant
      receptor expressed from SFV1-mCB(2) RNA exhibits properties, including ligand
      binding features, that are consistent with those for the native mCB(2) receptor.
      However, the presence of both 26 and 40kDa receptor species is consistent with
      alternative translation from two AUG start sites using the SFV1-mCB(2) RNA
      expression system.

PMID- 12787874
TI  - Effect of 20-epi-1alpha,25-dihydroxyvitamin D3 on the proliferation of human
      neuroblastoma: role of cell cycle regulators and the Myc-Id2 pathway.
AB  - The antiproliferative effects of 1alpha,25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)] and its epimer, 20-epi-1alpha,25-dihydroxyvitamin D(3) [20-epi
      1,25(OH)(2)D(3)], in six human neuroblastoma (NB) cell lines (SH-SY5Y, NB69, SK-N
      AS, IMR5, CHP134, and NGP) were investigated. We determined the ability of
      1,25(OH)(2)D(3) and 20-epi-1,25(OH)(2)D(3) to influence cell viability by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell
      proliferation by bromodeoxyuridine (BrdU) incorporation, and their antineoplastic
      effect on colony formation in a soft agar assay. A concentration-dependent
      decrease in cell viability, inhibition of DNA synthesis, and suppression of
      clonal proliferation was observed with both compounds. 20-epi-1,25(OH)(2)D(3) was
      more potent in suppressing the proliferation of all six NB cell lines. To
      understand the mechanisms of action, we examined the effect of 20-epi
      1,25(OH)(2)D(3) on the Myc-Id2 cell proliferative network and also on key
      regulators of the cell cycle. For the first time, we show that 20-epi
      1,25(OH)(2)D(3) down-regulated Myc and Id2 expression by western blot analysis.
      Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      analysis revealed that 20-epi-1,25(OH)(2)D(3) induced the expression of retinoic
      acid receptor-beta and p21(Cip1), and down-regulated the expression of cyclin D1
      resulting in decreased phosphorylation of retinoblastoma protein (pRB). In sum,
      we show that 20-epi-1,25(OH)(2)D(3) exerts strong antiproliferative effects by
      regulating key growth control networks (Myc-Id2-pRB) in NB cells.

PMID- 12787876
TI  - Fast repair of deoxythymidine radical anions by two polyphenols: rutin and
      quercetin.
AB  - The effects of rutin and quercetin on the repair of the deoxythemindine radical
      anion (dT*) were studied using the technique of pulse radiolysis. The radical
      anion of dT was formed by the reaction of hydrated electron with dT. After pulse
      irradiation of nitrogen-saturated aqueous solutions containing dT, 0.2M t-BuOH
      and either rutin or quercetin, the initially formed dT*(-), detected
      spectrophotometrically, rapidly decayed with the concurrent formation of the
      radical anion of rutin or quercetin. The results indicated that dT*(-) can be
      rapidly repaired by rutin or quercetin. The rate constants of the repair
      reactions were determined to be 3.1 and 4.1 x 10(9)M(-1)s(-1) for rutin and
      quercetin, respectively. With substitution by glycosyl groups at C(3)-OH bond
      being neighbor to C(4) keto group, which is the active site for electron
      transfer, rutin has a lower repair reaction rate constant toward dT*(-) than
      quercetin. Together with findings from our previous studies, the present results
      demonstrated that nonenzymatic fast repair may be a universal form of repair
      involving phenolic antioxidants.

PMID- 12787875
TI  - Metabolism of 26,26,26,27,27,27-F6-1alpha,25-dihydroxyvitamin D3 by CYP24:
      species-based difference between humans and rats.
AB  - The compound 26,26,26,27,27,27-F(6)-1alpha,25(OH)(2)D(3) is a hexafluorinated
      analog of the active form of Vitamin D(3). The enhanced biological activity of
      F(6)-1alpha,25(OH)(2)D(3) is considered to be related to a decreased metabolic
      inactivation of the compound in target tissues such as the kidneys, small
      intestine, and bones. Our previous study demonstrated that CYP24 is responsible
      for the metabolism of F(6)-1alpha,25(OH)(2)D(3) in the target tissues. In this
      study, we compared the human and rat CYP24-dependent metabolism of F(6)
      1alpha,25(OH)(2)D(3) by using the Escherichia coli expression system. In the
      recombinant E. coli cells expressing human CYP24, bovine adrenodoxin and NADPH
      adrenodoxin reductase, F(6)-1alpha,25(OH)(2)D(3) was successively converted to
      F(6)-1alpha,23S,25(OH)(3)D(3), F(6)-23-oxo-1alpha,25(OH)(2)D(3), and the putative
      ether compound with the same molecular mass as F(6)-1alpha,25(OH)(2)D(3). The
      putative ether was not observed in the recombinant E. coli cells expressing rat
      CYP24. These results indicate species-based difference between human and rat
      CYP24 in the metabolism of F(6)-1alpha,25(OH)(2)D(3). In addition, the metabolite
      with a cleavage at the C(24)z.sbnd;C(25) bond of F(6)-1alpha,25(OH)(2)D(3) was
      detected as a minor metabolite in both human and rat CYP24. Although F(6)
      1alpha,23S,25(OH)(3)D(3) and F(6)-23-oxo-1alpha,25(OH)(2)D(3) had a high affinity
      for Vitamin D receptor, the side-chain cleaved metabolite and the putative ether
      showed extremely low affinity for Vitamin D receptor. These findings indicate
      that human CYP24 has a dual pathway for metabolic inactivation of F(6)
      1alpha,25(OH)(2)D(3) while rat CYP24 has only one pathway. Judging from the fact
      that metabolism of F(6)-1alpha,25(OH)(2)D(3) in rat CYP24-harboring E. coli cells
      is quite similar to that in the target tissues of rat, the metabolism seen in
      human CYP24-harboring E. coli cells appear to exhibit the same metabolism as in
      human target tissues. Thus, this recombinant system harboring human CYP24 appears
      quite useful for predicting the metabolism and efficacy of Vitamin D analogs in
      human target tissues before clinical trials.

PMID- 12787877
TI  - Influence of parenteral iron preparations on non-transferrin bound iron uptake,
      the iron regulatory protein and the expression of ferritin and the divalent metal
      transporter DMT-1 in HepG2 human hepatoma cells.
AB  - It is widely assumed that standard parenteral iron preparations are degraded in
      the reticuloendothelial cells and that the iron is subsequently incorporated into
      transferrin. Hepatocytes or other epithelial cells have been considered as not
      affected. We show that this picture should be carefully reconsidered. By using
      the human hepatoma cell line HepG2 we showed that the parenteral iron
      preparations ferric saccharate and ferric gluconate donated iron to the cells as
      efficiently as low molecular weight iron and stimulated non-transferrin bound
      iron uptake. This led to inactivation of the iron regulatory protein 1 and to an
      increase in the expression of ferritin and of the divalent metal transporter (DMT
      1). Ferric dextran was only a weak stimulator of ferritin and DMT-1 expression.
      The observed changes in iron metabolism occurred at concentrations of parenteral
      iron that can also be found in the plasma of patients after i.v. infusion. We
      conclude that parenteral iron also influences the iron metabolism of non
      reticuloendothelial cells like HepG2 cells. Further the increase in the
      expression of the transporter DMT-1 in HepG2 cells after iron treatment is in
      contrast to the regulation in the duodenum and may be involved in the upregulated
      uptake of potentially toxic non-transferrin bound iron from the circulation to
      store it in the non-toxic form of ferritin.

PMID- 12787878
TI  - Toxic effects of copper-based antineoplastic drugs (Casiopeinas) on mitochondrial
      functions.
AB  - To elucidate some of the subcellular and biochemical mechanisms of toxicity of
      metal-based antineoplastic drugs, mitochondria and cells were exposed to
      Casiopeinas), a new class of copper-based compounds with high antineoplastic
      activity. The rates of respiration and swelling, the H(+) gradient, and the
      activities of succinate (SDH) and 2-oxoglutarate dehydrogenases (2-OGDH) and
      ATPase were measured in mitochondria isolated from rat liver, kidney, heart, and
      hepatoma AS-30D. Also, oligomycin-sensitive respiration and ATP content in
      hepatoma AS-30D cells were determined. Casiopeinas) (CS) II-gly and III-i
      inhibited the rates of state 3 and uncoupled respiration in mitochondria. CS II
      was 10 times more potent than CS III. The sensitivity to CS II was 4-5-fold
      higher in mitochondria incubated with 2-OG than with succinate. Thus, at low
      concentrations (< or =10 nmol (mg protein)(-1); 10 microM), CS II disturbed
      mitochondrial functions only when 2-OG was present, due to a specific inhibition
      of 2-OGDH. At high concentrations (> or =15nmol (mg protein)(-1)), CS II-induced
      stimulation of basal respiration, followed by a strong inhibition, which
      correlated with K(+)-dependent swelling and cytochrome c release, respectively;
      K(+)-channel openers induce a similar mitochondrial response. Mitochondria from
      liver, kidney and hepatoma showed a similar sensitivity towards CS II, whereas
      heart mitochondria were more resistant. Oxidative phosphorylation and ATP content
      were also decreased in tumor cells by CS II. The data suggested that CS affected
      several different mitochondrial sites, bringing about inhibition of respiration
      and ATP synthesis, which could compromise energy-dependent processes such as
      cellular duplication.

PMID- 12787879
TI  - Long-term-desensitization of prostacyclin receptors is independent of the C
      terminal tail.
AB  - Persistent stimulation of the G(s) protein-coupled prostacyclin receptor (IP-R)
      causes its slow desensitization in a variety of cell types, a significant
      desensitization requiring several hours. To evaluate the role of the human IP-R C
      terminus in desensitization and agonist-induced internalization, a C-terminally
      truncated hIP-receptor was generated. The C-terminal 68 amino acid residues were
      deleted by introduction of a stop codon for exchange of the original S319 codon
      (termed D318 mutant). Wild-type (WT) and truncated receptor were expressed in
      COS1 cells. Pretreatment of cells with the stable prostacyclin mimetic cicaprost
      (200 nM) desensitized cAMP production via WT and D318 receptors to similar
      extents. The cAMP response of WT and D318, respectively, was reduced by
      approximately 50% of maximal cAMP formation after 8 hr of continuous agonist
      stimulation, indicating significant long-term desensitization. Moreover, agonist
      promoted sequestration of WT and D318 C-terminally tagged with green fluorescent
      protein was demonstrated, indicating that receptor internalization was not
      prevented by truncation of the C-terminus. These results demonstrated that long
      term desensitization and sequestration of hIP-R did not depend on structures
      located in the hIP-R C-terminus.

PMID- 12787880
TI  - Enforced expression of the tumor suppressor p53 renders human leukemia cells
      (U937) more sensitive to 1-[beta-D-arabinofuranosyl]cytosine (ara-C)-induced
      apoptosis.
AB  - The effects of enforced expression of p53 on the sensitivity of p53(-/-) human
      monocytic leukemia cells (U937) to apoptosis following exposure to the S-phase
      specific antimetabolite 1-[beta-D-arabinofuranosyl]cytosine (ara-C) were
      examined. Cells were stably transfected with a plasmid containing a chimeric DNA
      construct encoding a temperature-sensitive p53 variant (135(ala-->val)), which
      transactivates at 32 degrees but is non-functional at 37 degrees. A significant
      reduction in the S-phase population was observed in ptsp53 mutants incubated at
      32 degrees. Nevertheless, while vector controls did not exhibit differential
      sensitivity to ara-C at 32 degrees versus 37 degrees, temperature-sensitive p53
      mutants displayed a significant increase in apoptosis at the permissive
      temperature. This was not accompanied by increased ara-CTP formation, DNA
      incorporation of [3H]ara-C, or altered expression of Bcl-2 or Bax. Enhanced
      sensitivity was associated with increased mitochondrial injury (e.g. cytochrome c
      release), caspase activation, and loss of clonogenic survival. Significantly,
      ptsp53 cells synchronized in S phase were markedly more sensitive to ara-C
      mediated mitochondrial injury and apoptosis at 32 degrees, indicating that wild
      type p53 specifically enhances the susceptibility of this subpopulation to ara-C
      lethality. Consistent with these results, transient transfection of human wild
      type p53 cDNA rendered parental U937 cells more sensitive to ara-C-mediated cell
      death. Collectively, these findings indicate that p53 expression renders S-phase
      U937 cells more susceptible to ara-C-mediated mitochondrial dysfunction,
      cytochrome c release, apoptosis, and loss of clonogenic survival without
      enhancing ara-C metabolism. Such findings raise the possibility that loss of
      functional p53 activity allows leukemia cells to circumvent ara-C lethality.

PMID- 12787881
TI  - Dual inhibition of topoisomerase I and tubulin polymerization by BPR0Y007, a
      novel cytotoxic agent.
AB  - Through the screening of DNA topoisomerase I (Top I) inhibitors, a new cytotoxic
      agent, BPR0Y007 [2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone], was
      identified. BPR0Y007 was less potent than camptothecin (CPT) in the inhibition of
      Top I in vitro. Also, in vitro data showed that BPR0Y007 induces DNA cleavage in
      the presence of Top I at micromolar concentrations, with a cleavage specificity
      similar to that of CPT. High concentrations of BPR0Y007 did not produce
      detectable DNA unwinding, suggesting that BPR0Y007 is not a DNA intercalator.
      However, BPR0Y007 displaced Hoechst 33342 dye, suggesting that BPR0Y007 binds to
      DNA at the Hoechst 33342 binding site. Furthermore, BPR0Y007 generated protein
      linked DNA breaks in a cell-based study. Cell cycle analysis demonstrated that
      the cell cycle effect of BPR0Y007 differs from that of CPT. Cells accumulated in
      the S-phase when treated with high concentrations of CPT, whereas cells
      accumulated gradually in the G(2)/M phase when treated with increasing
      concentrations of BPR0Y007. Further studies showed that BPR0Y007 inhibits tubulin
      polymerization in vivo and in vitro, and induces apoptosis in a concentration
      dependent manner. No cross-resistance with BPR0Y007 was observed in CPT-, VP-16-,
      or vincristine-resistant cell lines. The IC(50) of BPR0Y007 for various human
      cancer cell lines ranged from 1 to 8 microM. Taken together, these results
      suggest that BPR0Y007 acts on both Top I and tubulin. Given its unique
      biochemical mechanisms of action, BPR0Y007 warrants exploration as an antitumor
      compound.

PMID- 12787882
TI  - Reduced concentrations of serum enhance the antiproliferative activity of
      retinoid-related molecules and accelerate the onset of apoptosis.
AB  - Retinoid-related molecules (RRMs) that are selective agonists for the retinoic
      acid receptor-gamma and one retinoid antagonist are potent inducers of apoptosis
      in various cancer cell lines. This cell-killing activity makes them promising
      candidates for their use as anticancer drugs. We have observed that reducing the
      amount of serum in the cell culture medium significantly increased the
      antiproliferative activity of these RRMs in a serum concentration dependent
      manner. The induction of caspase activity, DNA fragmentation, and externalization
      of phosphatidylserine by the RRMs was markedly reduced when cells were treated in
      medium containing 10% serum, as compared to cells treated in low serum. High
      concentrations of serum also inhibited the activation of stress kinases by RRMs
      and higher amounts of the retinoid derivatives were necessary to cause
      quantitatively similar effects as compared to treatments in medium containing low
      serum. We have demonstrated that high concentrations of serum in the culture
      medium prevented the intracellular accumulation of MX3350-1 (agonist). Moreover,
      pre-incubation of cells in low serum-containing medium accelerated the onset of
      apoptosis as evidenced by the rapid activation of caspases and formation of
      apoptotic bodies. The release of cytochrome c and Smac induced by RRMs occurred
      earlier in cells that had been pre-incubated in 0.5% serum, while the activation
      of JNK and p38 stress kinases was unaffected.

PMID- 12787883
TI  - Activation of deoxycytidine kinase by gamma-irradiation and inactivation by
      hyperosmotic shock in human lymphocytes.
AB  - Deoxycytidine kinase (dCK) is a key enzyme in the intracellular metabolism of
      deoxynucleosides and their analogues, phosphorylating a wide range of drugs used
      in the chemotherapy of leukaemia and solid tumours. Previously, we found that
      activity of dCK can be enhanced by incubating primary cultures of lymphocytes
      with substrate analogues of the enzyme, as well as with various genotoxic agents.
      Here we present evidence that exposure of human lymphocytes to 0.5-2 Gy dosage of
      gamma-radiation as well as incubation of cells with calyculin A, a potent
      inhibitor of protein phosphatase 1 and 2A, both elevate dCK activity without
      changing the level of dCK protein. When cells were gamma-irradiated in the
      presence of calyculin A, a more pronounced activation of dCK was observed. In
      contrast, both basal and stimulated dCK activities were reduced by hyperosmotic
      treatment of the cells. DNA repair determined by the Comet assay and by thymidine
      incorporation was induced by irradiation. Complete repair of gamma-irradiated DNA
      was detected within 1 hr following the irradiation along with dCK activation, but
      the rate of repair was not accelerated by calyculin A. These data provide
      evidence for the activation of dCK upon DNA damage and repair that seems to be
      mediated by phosphorylation of the enzyme, suggesting the role of dCK in DNA
      repair processes.

PMID- 12787884
TI  - Sarin (nerve agent GB)-induced differential expression of mRNA coding for the
      acetylcholinesterase gene in the rat central nervous system.
AB  - We carried out a time-course study on the effects of a single intramuscular
      (i.m.) dose (0.5x LD(50)) of sarin (O-isopropyl methylphosphonofluoridate), also
      known as nerve agent GB, on the mRNA expression of acetylcholinesterase (AChE) in
      the brain of male Sprague-Dawley rats. Sarin inactivates the enzyme AChE which is
      responsible for the breakdown of the neurotransmitter acetylcholine (ACh),
      leading to its accumulation at ACh receptors and overstimulation of the
      cholinergic system. Rats were treated with 50 microg/kg of sarin (0.5x LD(50)) in
      1 mL saline/kg and terminated at the following time points: 1 and 2 hr and 1, 3,
      and 7 days post-treatment. Control rats were treated with normal saline. Total
      RNA was extracted, and northern blots were hybridized with cDNA probes for AChE
      and 28S RNA (control). Poly-A RNA from both treated and control cortex was used
      for reverse transcription-polymerase chain reaction (RT-PCR)-based verification
      of the data from the northern blots. The results obtained indicate that a single
      (i.m.) dose of sarin (0.5x LD(50)) produced differential induction and
      persistence of AChE mRNA levels in different regions of the brain. Immediate
      induction of AChE transcripts was noted in the brainstem (126+/-6%), cortex
      (149+/-4%), midbrain (153+/-5%), and cerebellum (234+/-2%) at 1 hr. The AChE
      expression level, however, increased over time and remained elevated after a
      decline at 1 day in the previously shown more susceptible brainstem. The
      transcript levels remained elevated at a later time point (3 days) in the
      midbrain, after a dramatic decline at day 1 (110+/-2%). In the cortex, transcript
      levels came down to control values by day 1. The cerebellum also showed a decline
      of the elevated levels observed at 2 hr (275+/-2%) to control values by day 1. RT
      PCR analysis of the AChE transcript at 30 min in the cortex showed an induction
      to 213+/-3% of the control level, confirming the expression pattern obtained by
      the northern blot data. The immediate induction followed by the complex pattern
      of the AChE mRNA time-course in the CNS may indicate that the activation of both
      cholinergic-related and unrelated functions of the gene plays an important role
      in the pathological manifestations of sarin-induced neurotoxicity.

PMID- 12787885
TI  - Inhibition of the norepinephrine transporter function in cultured bovine adrenal
      medullary cells by bisphenol A.
AB  - We report here the effects of an environmental estrogen, bisphenol A, on
      norepinephrine (NE) transporter function in cultured bovine adrenal medullary
      cells. The effects of bisphenol A were compared to those of 17beta-estradiol.
      Bisphenol A significantly inhibited [3H]NE uptake by the cells in a concentration
      dependent manner (1-100 microM). Kinetic analysis revealed that bisphenol A, as
      well as 17beta-estradiol, noncompetitively inhibited [3H]NE uptake. Bisphenol A
      and 17beta-estradiol inhibited the specific binding of [3H]desipramine to plasma
      membranes isolated from bovine adrenal medulla. As shown by Scatchard analysis of
      [3H]desipramine binding, bisphenol A increased the dissociation constant (K(d))
      and decreased the maximal binding (B(max)), indicating a mixed type of
      inhibition. 17beta-Estradiol increased the K(d) without altering the B(max),
      thereby indicating competitive inhibition. The present findings suggest that
      bisphenol A inhibits the function of the NE transporter by acting on a site
      different from that of 17beta-estradiol in the adrenal medulla and probably in
      the brain noradrenergic neurons.

PMID- 12787886
TI  - The fusion of IGF I with stromal cell-derived factor I or alpha1 proteinase
      inhibitor alters their mitogenic or chemotactic activities while keeping their
      ability to inhibit HIV-1-gp120 binding.
AB  - It has been previously reported that insulin-like growth factor I (IGF I)
      decreases in AIDS patients with wasting, a condition that is partially prevented
      by combined IGF I growth hormone therapy. By generating bifunctional proteins of
      IGF I and stromal cell-derived factor 1alpha (SDF-1alpha) or alpha1 proteinase
      inhibitor (API), two proteins known to prevent HIV infection, it may be possible
      to improve the therapeutic effectiveness of these compounds for the treatment of
      AIDS-mediated wasting. SDF-1alpha or the M351E-M358L mutant of API were attached
      at the C-terminal end of IGF I and synthesized by a stable insect cell expression
      technique. The IGF I-SDF-1alpha chimera reduced the enhancement of thymidine
      incorporation into bovine fetal erythroid cells observed in the presence of
      insect cell produced IGF I alone. It also decreased the SDF-1 and IGF I
      stimulated hematopoietic cell migration, without losing the capacity to compete
      with the binding of HIV-1 (IIIB)-surface glycoprotein gp120. The IGF I-API
      chimera displayed the same mitogenic activity and a similar, but lower
      chemotactic activity than IGF I in the assays mentioned above. It had a
      comparable anti-elastase activity to that observed with a previously described
      IGF II-API fusion protein with the single mutation M351E. The binding of gp120 to
      a murine hematopoietic cell line was stimulated by human neutrophil elastase (25
      100 nM) and inhibited by IGF I-API. In conclusion, the linkage of IGF I with SDF
      1 or API can alter some biological functions of the single components of the
      chimera while keeping their ability to compete with HIV-1-gp120 binding.

PMID- 12787888
TI  - Endogenous nitric oxide does not modulate mesenteric mast cell degranulation in
      rats.
AB  - The inhibitory effects of endogenous nitric oxide could explain the decreased
      mesenteric mast cell degranulation after anaphylaxis in genetically hypertensive
      rats (SHR). SHR and normotensive rats (NT) were sensitized to ovalbumin and
      challenged 14 days later. Degranulation of mast cells was assessed in duodenum,
      mesentery and skin by increased microvascular permeability using extravasation of
      Evans blue dye (20mg/kg, i.v.), and in the mesentery also by light microscopy
      after staining with toluidine blue. Pretreatment with an inhibitor of nitric
      oxide synthesis, L-NAME (30 mg/kg, i.v.) did not change dye extravasation after
      immunological challenge or after compound 48/80 in mesentery of either SHR or NT.
      PCA was also defective in SHR. Pretreatment with L-NAME did not affect either the
      defective PCA in SHR or the normal PCA reaction in NT. Our results show that
      inhibition by endogenous nitric oxide is not the cause of the defective mast cell
      degranulation in the SHR nor did it modulate degranulation of mesenteric or skin
      mast cells in NT.

PMID- 12787887
TI  - Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on
      human synovial fibroblasts and mouse macrophages.
AB  - We previously reported that nobiletin (5,6,7,8,3',4'-hexamethoxy flavone), a
      citrus polymethoxy flavonoid, effectively interferes with the production of
      promatrix metalloproteinase (proMMP)-9/progelatinase B in rabbit synovial
      fibroblasts [J. Rheumatol. 27 (2000) 20]. In this paper, we further examine the
      effects of nobiletin on the production of cyclooxygenases (COXs), prostaglandin
      (PG) E(2), and proinflammatory cytokines in human synovial fibroblasts and the
      mouse macrophage J774A.1 cell line. Nobiletin suppressed the interleukin (IL)-1
      induced production of PGE(2) in human synovial cells in a dose-dependent manner
      (<64 microM). Additionally, it selectively downregulated COX-2, but not COX-1
      mRNA expression. Nobiletin also interfered with the lipopolysaccharide-induced
      production of PGE(2) and the gene expression of proinflammatory cytokines
      including IL-1alpha, IL-1beta, TNF-alpha and IL-6 in mouse J774A.1 macrophages.
      In addition, nobiletin downregulated the IL-1-induced gene expression and
      production of proMMP-1/procollagenase-1 and proMMP-3/prostromelysin-1 in human
      synovial fibroblasts. In contrast, production of the endogenous MMP inhibitor,
      TIMP-1, was augmented by nobiletin. These anti-inflammatory actions of nobiletin
      are very similar to those of anti-inflammatory steroids such as dexamethasone,
      and the upregulation of TIMP-1 production is a unique action of nobiletin.
      Therefore, these results further support the notion that nobiletin is likely to
      be a candidate for characterization as a novel immunomodulatory and anti
      inflammatory drug.

PMID- 12787889
TI  - Analysis of A2a receptor-deficient mice reveals no significant compensatory
      increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid
      organs.
AB  - Although recent genetic and pharmacologic in vivo studies of acute inflammation
      models in mice demonstrated that the cyclic AMP-elevating A2a receptor plays a
      non-redundant role in protection from excessive acute inflammatory tissue damage
      and in the down-regulation of proinflammatory cytokine production, it remained to
      be established whether genetic deficiency of the A2a receptor is accompanied by a
      compensatory up-regulation of the cAMP-elevating A2b receptor and/or other
      adenosine receptors. Here, we show that most of the cAMP response to adenosine is
      abolished in lymphoid tissues of A2a receptor-deficient mice, although some
      response remains in splenocytes. No significant changes were observed in A2b, A1,
      and A3 mRNA levels in the thymus or lymph nodes of A2a receptor-deficient mice,
      but small increases in mRNA expression of these receptors were detected in the
      spleen. These data suggest that regulation of the expression of A2b, A1, and A3
      receptors is not affected significantly by the absence of A2a receptors and may
      provide further explanation of earlier in vivo observations of increased tissue
      damage and of longer persistence of proinflammatory cytokines in animals with
      inactivated A2a receptors.

PMID- 12787890
TI  - Modification of intracellular free calcium in cultured A10 vascular smooth muscle
      cells by exogenous phosphatidic acid.
AB  - Exogenous phosphatidic acid (PA) was observed to produce a concentration
      dependent increase in [Ca(2+)](i) in cultured A10 vascular smooth muscle cells.
      Preincubation of cells with sarcoplasmic reticulum Ca(2+)-ATPase inhibitors
      (cyclopiazonic acid and thapsigargin), a phospholipase C inhibitor (2-nitro-4
      carboxyphenyl-N,N-diphenylcarbamate), inositol 1,4,5-trisphosphate receptor
      antagonists (2-aminoethoxydiphenyl borate and xestospongin), and an activator of
      protein kinase C (PKC) (phorbol 12-myristate 13-acetate) depressed the PA-evoked
      increase in [Ca(2+)](i). Although EGTA, an extracellular Ca(2+) chelator,
      decreased the PA-induced increase in [Ca(2+)](i), sarcolemmal Ca(2+)-channel
      blockers (verapamil or diltiazem) did not alter the action of PA. On the other
      hand, inhibitors of PKC (bisindolylmaleimide I) and G(i)-protein (pertussis
      toxin) potentiated the increase in [Ca(2+)](i) evoked by PA significantly. These
      results suggest that the PA-induced increase in [Ca(2+)](i) in vascular smooth
      muscle cells may occur upon the activation of phospholipase C and the subsequent
      release of Ca(2+) from the inositol 1,4,5-trisphosphate-sensitive Ca(2+) pool in
      the sarcoplasmic reticulum. This action of PA may be mediated through the
      involvement of PKC.

PMID- 12787891
TI  - Heterodimer requirement for gene regulation by Vitamin D in variant OK cells.
AB  - OK cells are a transformed cell line derived from opossum kidney proximal tubule
      cells. Prior studies have utilized this cell line to study both positive and
      negative transcriptional responses to Vitamin D. However, there was a noticeable
      decrease in sensitivity on the part of these cells to respond to Vitamin D
      treatment in transfection assays, particularly when assessing transcriptional
      activity from a heterologous promoter construct that used the chicken parathyroid
      hormone (cPTH) repressor Vitamin D response element (VDRE). Western blotting
      revealed the apparently diminished expression of both the Vitamin D receptor
      (VDR) together with its heterodimeric DNA-binding partner, the retinoid X
      receptor (RXR), in these cellular extracts. Co-transfection of either a VDR or
      RXR expression vector alone had little effect on hormone-dependent enhancer
      transcriptional activity from the human osteocalcin (hOC) reporter construct, or
      the degree of repression from the cPTH construct. Indeed, significant effects on
      repressor or enhancer activity were only observed in these cells when expression
      vectors for both the VDR and RXR were simultaneously introduced into the cells
      via transfection experiments. Analogous results were obtained irrespective of the
      identity of RXR isoform; co-transfection of either RXRalpha or RXRbeta expression
      vectors together with the VDR-produced similar improvements in repressor
      activity. Titration of Vitamin D hormone under conditions of co-expression of the
      two receptors indicated that half-maximal responses were comparable for both
      VDREs and occurred at <1nM concentration. In summary, these results are
      consistent with prior in vitro studies indicating interaction of the VDR with
      these VDREs occurs as a heterodimer complex with RXR. The decreased expression of
      both heterodimer partners observed in these cells could explain the requirement
      for additional VDR/RXR expression, in particular in order to compensate for the
      reportedly lower binding affinity of the heterodimer with the repressor cPTH
      VDRE. The extent of expression of both heterodimer partners, therefore, may act
      to modulate the available responses to Vitamin D in target cells.

PMID- 12787892
TI  - Metabolism of steroidal anti-inflammatory antedrugs in vitro: methyl 3,20-dioxo
      11beta,17alpha,21-trihydroxy-1,4-pregnadiene-16alpha-carboxylate; its 9alpha
      fluorinated, and their 21-O-acyl derivatives.
AB  - The in vitro hydrolysis rates of steroidal anti-inflammatory antedrugs, methyl
      3,20-dioxo-11beta,17alpha,21-trihydroxy-1,4-pregnadiene-16alpha-carboxylate
      (P16CM), its 9alpha-fluorinated analogue (FP16CM), and their 21-O-acyl
      derivatives (P16CM-acetyl, FP16CM-acetyl, FP16CM-propionyl, FP16CM-valeryl, and
      FP16CM-pivalyl) were investigated in rat plasma. These steroids were synthesized
      based on the antedrug concept. P16CM and FP16CM were hydrolyzed to inactive
      steroid-16-carboxylate, with half-lives of 90.0 and 99.4 min, respectively. The
      metabolite was positively identified by NMR and elemental analysis. To determine
      the relative hydrolysis rate of the C21-O-acyl versus the C16-methoxycarbonyl
      group, P16CM- and FP16CM-21-O-acyl derivatives were also studied. The hydrolysis
      rates of all 21-O-acyl groups were much faster than that of the 16
      methoxycarbonyl group. The half-lives of P16CM-acetyl, FP16CM-acetyl, FP16CM
      valeryl, and FP16CM-propionyl were 6.3, 16.8, 23.2, and 18.4 min, respectively.
      On the other hand, FP16CM-pivalyl showed relatively slow hydrolysis rate (T(1/2):
      59.7 min). These results clearly indicate that 21-O-acyl group is metabolized
      first to active compound, P16CM or FP16CM, followed by the hydrolysis of 16
      methoxycarbonyl to corresponding inactive steroid-16-carboxylates as the major
      metabolites. Collectively, the results of the present study support the previous
      reports where decrease in adverse systemic effects without losing local anti
      inflammatory activity was attributed to the hydrolysis of the active agents to
      inactive acidic metabolites in the systemic circulation. This study thus shows
      that the incorporation of a 16-methoxycarbonyl coupled with a 21-O-acyl moiety
      may be a fundamentally sound synthetic strategy in the development of locally
      active anti-inflammatory steroids having reduced systemic adverse activities.

PMID- 12787893
TI  - Inclusion complexes of ketosteroids with beta-cyclodextrin.
AB  - Inclusion complexes of several steroid derivatives with beta-cyclodextrin (7)
      were studied in dimethylsulfoxide solution. The investigated molecules were
      ketosteroids with different functional groups on the skeleton: 3beta-acetoxypregn
      5-en-20-one (1), 3beta-acetoxypregna-5,16-dien-20-one (2), 3beta-acetoxyandrost-5
      en-17-one (3), 3beta-hydroxyandrost-5-en-17-one (4), 5alpha-androstane-3,17-dione
      (5) and 17beta-hydroxyandrost-4-en-3-one (6). Complex formation was monitored by
      two-dimensional ROESY experiments through the detection of intermolecular dipolar
      interactions. In case of inclusion complex formation, the steroid molecule
      penetrates the cavity of the cyclodextrin and dipole-dipole interactions (ROEs)
      can be detected between the glucose H-3 and H-5 protons inside the cyclodextrin
      cavity and the steroid skeletal protons. Intermolecular interactions were
      detected in all six cases. However, ROESY experiments provided data indicating
      only partial immersion (A and B ring of the steroid skeleton) in case of 1, 2 and
      6. On the contrary, compounds 3 and 5, showing the most correlation rich spectra,
      seem to fully immerse in the beta-cyclodextrin cavity.

PMID- 12787894
TI  - Glucocorticoid receptor interactions with glucocorticoids: evaluation by
      molecular modeling and functional analysis of glucocorticoid receptor mutants.
AB  - In the treatment of inflammatory skin diseases, there are some glucocorticoid
      (GC) double esters combining pronounced antiinflammatory activity and minor
      atrophogenic side effects. The reason, however, is only poorly understood. To
      investigate interactions of GCs with the ligand-binding domain of the
      glucocorticoid receptor (GR), we measured receptor-binding potency of a series of
      GC esters including their metabolites and performed a molecular modeling study
      using progesterone receptor crystal structure data. Ligand docking to the GR
      binding pocket showed good fitting of GC 17-esters corresponding to their high
      receptor-binding affinity, and unfavorable sterical interactions for GC 21-esters
      with substituents larger than propionate. Molecular dynamics simulations served
      to visualize induced fit procedures. Ligand docked GC conformations after
      dynamics simulations were used for generation of a 3D quantitative structure
      activity relationship model. Using a set of 11 steroids, this model showed a
      correlation coefficient (r(2)) of 0.98, a leave-one-out cross validation (q(2))
      of 0.79 and was able to predict binding affinity of further six ligands with a
      standard error of prediction of 0.33. Moreover, interactions of Asn-564 and Met
      639 with the steroids were investigated by studying GR mutants of these amino
      acids. Met-639 participates in hydrophobic interactions mainly with GC side
      chains, while Asn-564 forms a hydrogen bond to the C11-OH group of the steroid.
      Asn-564 is shown to be very important for ligand binding and even more for target
      gene activation and transcription factor repression.

PMID- 12787895
TI  - Development of a flow cytometric assay to study glucocorticoid receptor-mediated
      gene activation in living cells.
AB  - A flow cytometry-based reporter gene assay was developed and utilized to measure
      glucocorticoid receptor (GR)-mediated gene activation at the single cell level in
      living cells. A reporter gene was generated that contains two copies of the
      glucocorticoid response element and an E1b TATA box upstream of a destabilized
      enhanced green fluorescent protein. Glucocorticoid activation of the reporter
      gene in Cos-1 and HTC cell lines was measured in vivo by flow cytometry and was
      shown to be dose dependent, leading to an increase in total fluorescence of the
      cell population. Flow cytometric analysis indicated this increase in total
      fluorescence per sample resulted from an increase in the number of cells
      expressing the activated green fluorescent protein (GFP) reporter as well as an
      overall increase in the mean GFP fluorescence within cells. Activation of
      reporter gene activity was time dependent occurring as early as 1-2h after
      dexamethasone addition. Activation of the reporter gene was specific as it
      exhibited different sensitivities to a range of glucocorticoids and activation
      could be blocked with glucocorticoid receptor antagonists. Coexpression of the
      coactivator SRC-1a or P65 subunit of NF-kappa B with GR led to enhancement or
      repression, respectively. Taken together, these data suggest the reporter-based
      flow cytometry assay is an effective method for analyzing glucocorticoid receptor
      mediated gene expression at the single cell level in living cells.

PMID- 12787896
TI  - DNA slows dissociation of progesterone receptor-steroid ligand complexes.
AB  - Steroid ligands are known to affect the interactions of their respective
      receptors with DNA. In the present study, the possibility of DNA interference in
      progesterone receptor-ligand interactions was investigated. An oligonucleotide
      containing a hormone response element (HRE) was shown to decrease the
      dissociation rate of complexes of [3H]progesterone or [3H]16alpha,17alpha
      cycloalkanoprogesterones with PRs from rabbit and rat uterine cytosol. The extent
      to which the oligonucleotide affected the dissociation constant varied from about
      4- to 1.5-fold depending on the ligand structure and was ranked in the following
      order: progesterone>16alpha,17alpha-cyclopropanoprogesterone approximately
      16alpha,17alpha-cyclopentanoprogesterone>/=16alpha,17alpha-cyclohex-2'
      enoprogesterone approximately 6alpha-methyl-16alpha,17alpha
      cyclohexanoprogesterone>/=16alpha,17alpha-cyclohexanoprogesterone. The control
      oligonucleotide lacking HRE had a weak effect, if any, on the dissociation
      kinetics. No influence of the HRE-containing oligonucleotide on the equilibrium
      binding of ligands to PR was observed. The results suggest that the DNA partner
      affects binding of PR to its ligand.

PMID- 12787897
TI  - Air oxidation of 17-hydroxycorticosteroids catalyzed by cupric acetate: formation
      of hemiacetal dimers.
AB  - Hydrocortisone, cortexolone, hydrocortisone-17-butyrate, and budesonide were
      oxidized into alpha-ketoaldehydes by air exposure in the presence of Cu(OAc)(2).
      When free hydroxyl functions were present at position 17, hydrocortisone and
      cortexolone, the formed oxidation products, were identified as hemiacetal dimeric
      structures involving the free hydroxyl functions at position 17 and the newly
      formed aldehydes at position 21. Dimeric structures were established by using
      1H913C0 correlations (HSQC and HMBC) and 1H-1H correlations (COSY and ROESY). The
      hemiacetal function was further confirmed by reaction of the dimer formed from
      hydrocortisone with two equivalents of 3-methyl-2-benzotriazolinone hydrazine
      (MTBH), giving quantitatively two equivalents of the 3-methyl-2-benzotriazolinone
      hydrazone of 21-dehydrohydrocortisone. When no free hydroxyl function was present
      as in the case of hydrocortisone-17-butyrate and budesonide, the expected alpha
      ketoaldehydes were obtained.

PMID- 12787898
TI  - Crystal structure of steroidal monoenes obtained by reduction of the aromatic A
      ring of 13-ethyl-3-ethoxy-gona-1,3,5(10)-triene-11alpha,17beta-diol.
AB  - The crystal structures of 13-ethyl-gona-1(10)-ene-11alpha,17beta-diacetate (3b)
      and 13-ethyl-10alpha-gona-4-ene-11alpha,17beta-diacetate (5b), two steroidal
      monoenes obtained as minor products from the reduction, then acetylation, of the
      aromatic A ring of 13-ethyl-3-ethoxy-gona-1,3,5(10)-triene-11alpha,17beta-diol
      (1), were determined by X-ray diffraction. The conformations of the rings A, B,
      C, and D and the unusual stereochemistry at C-10 of the 10alpha-gona-4-ene (5b)
      are discussed.

PMID- 12787899
TI  - Short synthesis of 2-methoxyestradiol and 2-hydroxyestradiol.
AB  - The estrogen metabolite 2-methoxyestradiol was synthesized from estradiol bis-THP
      ether which was 2-hydroxylated using the superbase LIDAKOR, trimethyl borate, and
      H(2)O(2), then methylated and deprotected to obtain 2-methoxyestradiol in three
      steps and 61% yield. 2-Hydroxyestradiol was obtained by deprotecting the 2
      hydroxyestradiol bis-THP-ether from the first step.

PMID- 12787900
TI  - 1alpha,3beta,5beta-trihydroxy-24-methylenecholestan-6-one: a novel steroid from a
      soft coral Sinularia gibberosa.
AB  - A novel steroid, 1alpha,3beta,5beta-trihydroxy-24-methylenecholestan-6-one
      (gibberoketosterol) (1), along with four known steroids, was isolated from the
      lipophilic extracts of a Taiwanese soft coral Sinularia gibberosa. The structure
      of the new metabolite was determined on the basis of extensive spectral analyses
      and chemical reaction. The relative stereochemistry of gibberoketosterol was
      established by the NOESY experiments and analysis of the pyridine-induced
      deshielding effect of the axial hydroxy groups. Gibberoketosterol is the first
      example of 1alpha,3beta,5beta-trihydroxy-6-oxosteroids isolated from natural
      sources and was found to exhibit a moderate cytotoxicity against the growth of
      Hepa59T/VGH cancer cells.

PMID- 12787901
TI  - Metabolism of [6,7-3H, 35S] estradiol 17-sulfate in rats.
AB  - To confirm whether or not the sulfo group of estradiol 17-sulfate (ES) is removed
      during in vivo metabolism in rats, the doubly labeled conjugate [6,7-3H, 35S] ES
      was injected into rats, and its biliary and urinary metabolites were determined
      by reverse isotope dilution method (RIDM). In male rats, the major radioactivity
      was detected in biliary disulfate fraction, which was composed of mainly ES and
      its two minor metabolites, 2-hydroxyestradiol 17-sulfate (2-OH-ES) and 2
      methoxyestradiol 17-sulfate (2-MeO-ES). In female rats, in contrast, the
      radioactivity was dispersed into three fractions:biliary monosulfate, biliary
      disulfate, and urinary monosulfate fractions (Frs.) In both monosulfate Frs.,
      7beta-hydroxyestradiol 17-sulfate was detected as the major metabolite followed
      by 6alpha-, 6beta-, and 15beta-hydroxyestradiol 17-sulfates. Like male rats, 2-OH
      ES and 2-Meo-ES as the minor products were detected in biliary disulfate
      fraction. The isotope ratios of ES and its metabolites in both sexes were
      essentially the same as that of the dose except that of 6alpha-hydroxylated
      metabolite, which may be derived from the loss of the tritium labeled at C6.
      These results confirm the occurrence of the direct metabolism of ES in rats.

PMID- 12787902
TI  - Influence of local molecular motions on the determination of 1H-1H internuclear
      distances measured by 2D 1H spin-exchange experiments.
AB  - Analysis of spin-exchange build-up curves obtained by measurement of 2D 1H CRAMPS
      spectra of alpha-glycine was performed to evaluate the rate of 1H-1H spin
      exchange process with respect to the influence of variation in internal molecular
      motion. Differences in local motions significantly affect spin-exchange constants
      even in highly rigid organic solids with virtually uniform motion behavior. The
      polarization transfer between nonequivalent alpha-protons is described by the
      spin-exchange constant D=0.77 nm(2)ms(-1), while the polarization transfer
      involving spin exchange between alphaH and NH(3)(+) protons is characterized by
      D=0.24-0.21 nm(2)ms(-1). This significant decrease corresponds to rotation of
      hydrogen-bonded amino groups. Neglecting this variation in local spin-exchange
      constants the resulting calculated 1H-1H distance can be overestimated by up to
      100%. Complications following from relayed and back polarization transfer
      involving the nearest spins within one functional group (e.g., CH(2) and/or
      NH(3)(+)) and intermolecular spin exchange are discussed. It was shown that 2H
      quadrupolar splitting determined for selected sites directly correlates with the
      experimentally observed differences in spin-exchange coefficients. It is also
      demonstrated that a medium level quantum chemical calculation of molecular
      dynamics provides relevant data that can be used to estimate differences in
      molecular motions.

PMID- 12787903
TI  - Solid-state 13C and 1H spin diffusion NMR analyses of the microfibril structure
      for bacterial cellulose.
AB  - To obtain further information about the cause for the rather large splitting of
      the C4 resonance line into the downfield (C4D) and upfield (C4U) lines in CP/MAS
      13C NMR spectra for native cellulose, 13C and 1H spin diffusion measurements have
      been conducted by using different types of bacterial cellulose samples. In 13C
      spin diffusion measurements, the C4D resonance line is selectively inverted by
      the Dante pi pulse sequence and the 13C spin diffusion is allowed to proceed from
      the C4D carbons to other carbons including the C4U carbons with use of the 13C4
      enriched bacterial cellulose sample. The analysis based on the simple spin
      diffusion theory for the process experimentally observed reveals that the C4U
      carbons may be located at distances less than about 1 nm from the C4D carbons. In
      1H spin diffusion measurements, poly(vinyl alcohol) (PVA) films in which ribbon
      assemblies of bacterial cellulose are dispersed are employed and the 1H spin
      diffusion process is examined from the water-swollen PVA continuous phase to the
      dispersed ribbon assemblies by the 13C detection through the 1H-13C CP technique.
      As a result, it is found that the C4D and C4U carbons are almost equally
      subjected to the 1H spin diffusion from the PVA phase, indicating that the C4U
      carbons are not localized in some limited area, e.g. in the surfacial region, but
      are distributed in the whole area in the microfibrils. These experimental results
      suggest that the C4U carbons may exist as structural defects probably due to
      conformational irregularity associated with disordered hydrogen bonding of the
      CH(2)OH groups in the microfibrils.

PMID- 12787904
TI  - I-STMAS, a new high-resolution solid-state NMR method for half-integer
      quadrupolar nuclei.
AB  - In complement to the previously proposed multiple-quantum magic-angle-spinning
      (MQMAS) and satellite transition MAS (STMAS) sequences, we describe a new two
      dimensional high-resolution method, inverse-STMAS (I-STMAS) that allows second
      order quadrupolar averaging. Like STMAS, I-STMAS correlates second-order
      quadrupole dephasing occurring on coherences related to the central transition
      (CT) and satellite transitions (STs), but does it in a reverse manner: CT evolves
      during the t(1) period while STs are detected during t(2). Although STMAS and I
      STMAS are symmetric, there are some interesting and useful differences between
      the two methods. For example, we show that during the acquisition time t(2), it
      is possible to over-sample the data and then to process them to suppress the CT
      CT correlation resonance.

PMID- 12787905
TI  - Spin-lattice relaxation of 13CH3 groups in 13C-enriched aspirin after proton
      saturation.
AB  - We studied the spin-lattice relaxation of the 13C magnetisation, M(C), in 13C
      enriched single crystal of aspirin (only methyl carbons enriched to 99%) at the
      carbon resonance frequency of 54.5 MHz. After the carbon saturation the recovery
      appears exponential except below 30K, where it is biexponential due to the
      presence of the level crossing omega(t)=omega(C)+omega(H) (the symbols refer,
      respectively, to the tunnel frequency and the carbon and proton resonance
      frequencies in angular units). After the saturation of the proton magnetisation,
      M(H), the description of the M(C) recovery needs three exponentials. The
      evaluation of the time constants is easiest from the data in this case, since
      M(C) varies with time in an initial growth-subsequent decrease (or an initial
      decrease-subsequent growth depending on temperature) manner, instead of the
      monotonous growth after the carbon saturation. Experimental data agree
      semiquantitatively with the predictions of our recent model. According to the
      model the relaxation of M(C) is coupled to M(H) and the tunnel energy TE at
      temperatures below the minimum of the 13C relaxation time. Sufficiently above
      this minimum M(C) is coupled to M(H) and the rotational polarization (but not to
      TE) in agreement with experiment. Also the effect of torsional oscillations of a
      methyl group on the magnitude of various 13C-related transition rates was
      considered in detail. In aspirin the rates are reduced roughly by 10% and the
      reduction should become larger in samples with a larger tunnel splitting. The
      reduction also changes somewhat the angular dependence of these rates.

PMID- 12787906
TI  - 59Co, 23Na NMR and electric field gradient calculations in the layered cobalt
      oxides NaCoO2 and HCoO2.
AB  - 59Co and 23Na NMR has been applied to the layered cobalt oxides NaCoO(2) and
      HCoO(2) at three different magnetic field strengths (4.7, 7.1 and 11.7T). The
      59Co and 23Na quadrupole and anisotropic shift tensors have been determined by
      iterative fitting of the NMR line shapes at the three magnetic field strengths.
      Due to the large 59Co quadrupole interaction in NaCoO(2), a frequency-swept
      irradiation procedure was used to alleviate the limited bandwidth of the
      excitation. While the 59Co and 23Na shift and quadrupole coupling tensors in
      NaCoO(2) are found to be coincident and axially symmetric in agreement with the
      crystal symmetry requirements, the fits of the 59Co NMR spectra clearly show the
      presence of structural disorder in HCoO(2). The 23Na chemical shift anisotropy
      can be reproduced by shift tensor calculations using a point dipole model and
      considering that the magnetic susceptibility in NaCoO(2) is due to Van Vleck
      paramagnetism for Co(3+). Electric field gradient calculations using either the
      empirical point charge model or the ab initio full potential-linearized augmented
      plane wave method are compared with the experimental NMR data.

PMID- 12787907
TI  - High-field NMR in pulsed magnets.

PMID- 12787908
TI  - Parental exposure to low-dose X-rays in Drosophila melanogaster induces early
      emergence in offspring, which can be modulated by transplantation of polar
      cytoplasm.
AB  - In recent years there has been growing concern over the biological effects of low
      dose X-rays, but few studies have addressed this issue. Our laboratory had
      observed flies (Drosophila melanogaster) irradiated with low-dose X-rays tend to
      emerge earlier than normal flies. This observation led us to quantitatively
      examine the effects of low-dose X-irradiation on development in the fly.
      Following exposure of prepupal (day 5) flies to 0.5 Gy X-rays, the time to
      emergence was slightly shorter than in the sham controls. This tendency was
      increased when the X-ray exposure came during the pupal stage (day 7). In these
      flies, the time to eclosion decreased significantly, by an average of 30 h sooner
      than sham controls. A further experiment examined whether such radiation effects
      could be observed in the unexposed F1 generation of exposed individuals. Greater
      radiation effects on early F1 emergence were seen when the time between exposure
      and mating was 3 days, indicating an effect on early spermatid development. Early
      F1 emergence was also observed after exposure of female flies to X-rays during
      late previtellogeny. Furthermore, rapid emergence could be induced in the F1
      embryos of unexposed parents by transferring the polar cytoplasm (precursor cells
      of the germ cell line) from F1 embryos of exposed flies. These results show that
      radiation-induced effects can be transmitted to the next generation through the
      germ cell line.

PMID- 12787909
TI  - Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone
      marrow.
AB  - 5-Aminosalicylic acid (5ASA), a prescribed drug for ulcerative colitis, is a
      potent scavenger of oxygen-derived free radicals. The present study was
      undertaken to ascertain its ability to protect against radiation-induced damage.
      The drug dose-dependent effect, optimum time of drug administration and radiation
      dose-dependent effect (0-4 Gy) on in vivo radiation protection against
      micronuclei induction in polychromatic erythrocytes (PCE) and normochromatic
      erythrocytes (NCE) were studied in the bone marrow of mice. Intraperitoneal
      injection of 10-125 mg/kg of the drug 30 min before whole body irradiation with 3
      Gy produced a significant reduction in the frequency of micronucleated
      erythrocytes at 24 h after exposure. The optimum dose for protection without drug
      toxicity was 25 mg/kg body weight. Injection of 25 mg/kg of the drug 60 or 30 min
      before or within 15 min after 3 Gy whole body gamma-irradiation resulted in a
      significant decrease in the radiation-induced PCE and NCE with micronuclei (MPCE
      and MNCE) and an increase in the ratio of PCE to NCE (P/N), at 24 h post
      irradiation. Maximum effect was seen when the drug was administered 30 min before
      irradiation. Therefore, to study the radiation dose-response, mice were pre
      treated with 25 mg/kg of 5ASA 30 min before 1-4 Gy of gamma-irradiation.
      Radiation increased the MN frequency linearly (r(2)=0.99) with dose. Pre
      treatment with 5ASA significantly reduced the MN counts to 40-50% of the
      radiation (RT) alone values, giving a dose modification factor (DMF) of 2.02
      (MPCE) and 2.53 (MNCE). Irradiation resulted in a dose-dependent decline in the
      P/N ratio at all the doses of radiation studied. 5ASA produced a significant
      increase in the P/N ratio from that of irradiated controls, at all doses of
      radiations tested. These results show that 5ASA protect mice against radiation
      induced MN formation and mitotic arrest.

PMID- 12787911
TI  - Ability of antioxidants to prevent oxidative mutations in Salmonella typhimurium
      TA102.
AB  - An assay for the ability of antioxidants to prevent mutations induced by various
      oxidants in Salmonella typhimurium TA102 cells was developed. Protection against
      hydrogen-peroxide-induced mutagenicity was observed for quercetin, caffeic acid,
      ascorbic acid and dimethyl sulfoxide (used as a solvent for water-insoluble
      antioxidants). No protective effect was observed for green tea extract (weakly
      pro-oxidative), catechin, rutin, sinigrin, ferulic acid and alpha-tocopherol.
      Mutagenicity caused by tert-butyl hydroperoxide (tBOOH) was prevented most
      effectively by quercetin and ascorbic acid, whereas weaker effects were observed
      for green tea extract and for rutin, and no effect being observed for the other
      antioxidants tested. The results for hydrogen peroxide indicate iron chelation to
      be the most important protective mechanism. Radical scavenging appeared to be
      effective only with dimethyl sulfoxide and ascorbic acid, which are effective
      scavengers of hydroxyl radicals and were used here in high concentrations. It is
      proposed that the hydrogen-peroxide-induced mutations in the Salmonella cells are
      caused by hydroxyl radicals generated by iron ions closely associated with DNA.
      Protection against mutagenicity caused by tert-butyl hydroperoxide appears to
      occur mainly through the scavenging of alkoxyl and possibly of alkyl radicals.

PMID- 12787910
TI  - The radioenhancement of two human head and neck squamous cell carcinomas by 2'-2'
      difluorodeoxycytidine (gemcitabine; dFdC) is mediated by an increase in radiation
      induced residual chromosome aberrations but not residual DNA DSBs.
AB  - PURPOSE: The present study aimed at investigating if 2'-2' difluorodeoxycytidine
      (dFdC) radioenhancement was mediated by an effect on induction and/or repair of
      radiation-induced DNA DSBs and chromosome aberrations in cells with different
      intrinsic radiosensitivity. METHODS: Confluent human head and neck squamous cell
      carcinoma cell lines designated SCC61 and SQD9 were treated with 5 microM dFdC
      for 3 or 24 h prior to irradiation. DNA DSBs induction and repair were analyzed
      by PFGE. Radiation-induced chromosome aberrations were examined with a FISH
      technique. RESULTS: In both cell lines, dFdC did not modify radiation-induced DNA
      DSBs in a dose range between 0 and 40 Gy. After a single dose of 40 Gy, dFdC
      affected neither the kinetic of repair nor the residual amount of DNA DSBs up to
      4 h after irradiation. Whereas dFdC did not increase the induction of chromosome
      aberrations, after a single dose of 5 Gy, the percentage of aberrant cells and
      the number of aberrations per aberrant cells were significantly higher in
      combination with dFdC. CONCLUSION: Our data suggest that under experimental
      conditions yielding substantial radioenhancement, dFdC decreases the repair of
      genomic lesions inducing secondary chromosome breaks but has no effect on DNA
      DSBs repair as measured by PFGE.

PMID- 12787912
TI  - Validation of a novel assay for checkpoint responses: characterization of
      camptothecin derivatives in Saccharomyces cerevisiae.
AB  - The evolutionary conservation of pathways preserving genetic stability supports
      the use of a lower eukaryote such as the yeast Saccharomyces cerevisiae in
      screening for novel anti-neoplastic agents. Yeast is already established as a
      model system to characterize the cellular effects of the topoisomerase inhibitor
      and anti-cancer agent camptothecin (CPT). Here, we demonstrate that a recently
      developed two-hybrid based plate assay that visualizes the DNA damage-induced
      homomeric complex formation of the yeast checkpoint protein Rad17 correctly
      predicts the biological activity of the tested camptothecin derivatives. The used
      criteria for biological activity include lethality, cell cycle arrest and Rad53p
      phosphorylation, an essential signaling event during checkpoint activation.
      Surprisingly, although responsive to camptothecin and not without influence on
      drug sensitivity, Rad17p appears to be dispensable for cell cycle arrest and for
      Rad53p phosphorylation following treatment with camptothecin. Such a role is only
      uncovered if double-strand break repair is compromised.

PMID- 12787913
TI  - DNA damage and antioxidant defense in peripheral leukocytes of patients with Type
      I diabetes mellitus.
AB  - We determined relationship among DNA damage, nitric oxide (NO) and antioxidant
      defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as
      strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by
      the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a
      product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G
      Px) activity of the leukocytes were measured by spectrophotometric kits. Serum
      glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients,
      as expected. Differences in measured parameters between controls and patients
      were assessed in men and women separately. There was no significant difference
      between patient and control groups in neither men nor women for nitrite level.
      Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px
      activities of the leukocytes were found to be decreased in both men and women of
      patient group as compared to their respective controls. Significant correlations
      were determined between strand breakage and HbA(1c) (r = 0.37, P<0.05); Fpg
      sensitive sites and HbA(1c) (r = 0.59, P<0.01); Fpg-sensitive sites and glucose
      (r = 0.45, P<0.02); Fpg-sensitive sites and SOD (r = -0.48, P<0.02); HbA(1c) and
      SOD (r = -0.50, P<0.02). In conclusion, impaired antioxidant defense in
      leukocytes of patients with Type 1 DM may be one of the responsible mechanisms
      for increased DNA damage in those patients.

PMID- 12787914
TI  - Effect of caloric restriction on Hprt lymphocyte mutation in aging rats.
AB  - Caloric restriction (CR) reduces tumor incidence and retards aging in laboratory
      animals, including non-human primates. Because of the relationships among
      mutation, disease susceptibility, and aging, we investigated whether or not CR
      affects the accumulation of somatic cell mutations in aging animals. Starting at
      approximately 2 months of age, male CD rats (Harlan Sprague-Dawley-derived) were
      placed on different levels of dietary intake: ad libitum (AL) feeding, and 90%
      (10% CR), 75% (25% CR) and 60% (40% CR) of the total calories consumed by AL
      animals. At 3, 6, 12, and 24 months after the beginning of CR, Hprt mutant
      frequencies (MFs) were determined. The MFs measured in spleen lymphocytes from AL
      and CR rats sacrificed at 3 months of dietary restriction were similar for all
      dietary groups. However, the MFs at 6, 12, and 24 months of CR were significantly
      higher in AL-fed rats compared with animals on 40% CR: (4.5+/-0.4)x10(-6) versus
      (3.3+/-0.3)x10(-6) (P=0.032) in 6 months CR rats; (10.3+/-2.3)x10(-6) versus
      (7.3+/-1.2)x10(-6) in 12 months CR rats (P=0.04), and (18.3+/-3.2)x10(-6) versus
      (7.8+/-1.0)x10(-6) (P=0.001) in 24 months CR rats. In addition, rats receiving
      25% CR for 24 months had a MF, (10.7+/-2.0)x10(-6), between the 40% CR and AL
      rats. Multiplex PCR of the Hprt gene in mutant clones from 12 and 24 months 40%
      CR rats and the corresponding AL rats detected deletions in 42% of CR mutants and
      19% of AL mutants. Because of the difference in Hprt MF in the two groups, the
      estimated MF associated with deletions in CR rats was similar to the deletion MF
      in AL rats. This observation implies that the lower MF in CR rats is due to a
      reduction in smaller Hprt mutations (i.e. base substitutions and frameshifts).
      The pattern of smaller Hprt mutations from AL rats suggests that many were
      produced by reactive oxygen species (ROS). The results indicate that CR reduces
      the accumulation of spontaneous somatic cell mutation in aging rats, especially
      those caused by base substitutions and frameshifts.

PMID- 12787915
TI  - Induction and suppression of cytochrome P450 isoenzymes and generation of oxygen
      radicals by procymidone in liver, kidney and lung of CD1 mice.
AB  - Although chronic administration of procymidone (a widely used dicarboximide
      fungicide) leads to an increased incidence of liver tumors in mice, short-term
      genotoxicity studies proved negative. As cytochrome P450 (CYP) induction has been
      linked to non-genotoxic carcinogenesis, we investigated whether procymidone
      administration causes induction of CYP-dependent monooxygenases in liver, kidney
      and lung microsomes of male Swiss Albino CD1 mice after single or repeated (daily
      for three consecutive days) i.p. treatment with either 400 or 800 (1/10 or 1/20
      of the DL(50)) mgkg(-1) b.w. procymidone. CYP content and CYP3A1/2, 1A1, 1A2,
      2B1/2, 2E1, 2A, 2D9 and 2C11 supported oxidations were studied using either the
      regio- and stereo-selective hydroxylation of testosterone as multibiomarker or
      highly specific substrates as probes of various CYPs. While a single dose was
      uneffective, multiple procymidone administration lead to marked inductions of
      various monooxygenases: CYP3A1/2 in liver and lung (as measured by N
      demethylation of aminopyrine and testosterone 6 beta-hydroxylase); CYP2E1 in
      liver (p-nitrophenol hydroxylation); CYP1A1 in liver and kidney (deethylation of
      ethoxyresorufin). Several hydroxylations were induced in the liver, including the
      CYP2A-linked 7 alpha (14-fold) as well as 6 alpha (22-fold), 6 beta, 16 beta and
      2 beta hydroxylases. The pattern of inductions/suppressions recorded in the three
      different tissues suggests that procymidone exerts complex effects on the CYP
      profile. Tissue-specific trends included a large number of inductions in the
      liver and suppressions in the lung. The main inductions were corroborated by
      immunoblotting analyses and Northern blotting showed that inductions of CYP3A1/2,
      CYP2E1 and CYP1A1/2 were paralleled by increased mRNA levels. It was also found
      that CYP over-expression generates large amounts of reactive oxygen species
      (ROS), especially in liver. These data may explain why in vitro short-term
      genotoxicity studies on procymidone were negative, whereas in vivo long-term
      carcinogenesis studies turned out positive: long-term CYP induction (e.g. oxygen
      centered free radicals over-production) can have a co-carcinogenic and/or
      promoting potential.

PMID- 12787916
TI  - Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma
      from externally irradiated patient.
AB  - Molecular analysis of cDNA derived from a papillary thyroid carcinoma (PTC)
      (follicular variant of papillary thyroid carcinoma on histology) which developed
      in an externally irradiated patient 4 years after exposure identified a portion
      of the 5' region, exons 1-3, of the rfp gene juxtaposed upstream of the fragment
      encoding the tyrosine kinase (TK) domain of the ret gene. The fusion gene, termed
      Delta rfp/ret, was the result of a balanced chromosomal translocation t(6;10)
      (p21.3;q11.2) confirmed by interphase FISH painting, with breakpoints occurring
      in introns 3 and 11 of the rfp and ret genes, respectively. Both Delta rfp/ret
      and reciprocal ret/rfp chimeric introns had small deletions around breakpoints
      consistent with presumed misrepair of a radiation-induced double-strand DNA break
      underlying the rearrangement. No extensive sequence homology was found between
      the fragments flanking the breakpoints. The fusion protein retained the
      propensity to form oligomers likely to be mediated by a coiled-coil of the RFP
      polypeptide as assessed by a yeast two-hybrid system. NIH 3T3 fibroblasts stably
      transfected with a mammalian expression vector encoding full-length Delta RFP/RET
      readily gave rise to the tumors in athymic mice suggestive of high transforming
      potential of the fusion protein. Thus, the Delta rfp/ret rearrangement may be
      involved in a causative manner in cancerogenesis and provides additional evidence
      of the role of activated ret oncogene in the development of a subset of papillary
      thyroid carcinoma.

PMID- 12787917
TI  - Dietary low-dose sucrose modulation of IQ-induced genotoxicity in the colon and
      liver of Big Blue rats.
AB  - Earlier studies have indicated that sucrose increases 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ)-induced aberrant crypt foci in the colon. In this study, we
      investigated the role of sucrose in IQ-induced genotoxicity of the colon mucosa
      and liver. Big Blue rats were fed with IQ (20 ppm in feed) and/or sucrose (3.45
      or 6.85 wt.% in feed) for 3 weeks. IQ increased DNA strand breaks in the colon,
      whereas the mutation frequency was increased in the liver. The level of IQ
      induced DNA adducts was elevated in both colon mucosa cells and liver. In the
      liver, high sucrose intake increased the level of DNA adducts above that of IQ
      and low sucrose intake. Oxidative DNA damage detected in terms of 7-hydro-8-oxo
      2'-deoxyguanosine by HPLC-EC, or endonuclease III or formamidopyrimidine DNA
      glycosylase sensitive sites were unaltered in the colon and liver. Expression of
      ERCC1 and OGG1 mRNA levels were unaffected by IQ or sucrose feeding. Biomarkers
      of oxidative stress, including Vitamin C, malondialdehyde and protein oxidations
      (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) were unaltered in
      plasma and in liver. In conclusion, sucrose feeding increases IQ-induced
      genotoxicity in liver but not in colon, suggesting different mechanisms for
      sucrose and IQ in colon mutagenesis.

PMID- 12787918
TI  - Avoidance of bioflavonoid supplements during pregnancy: a pathway to infant
      leukemia?

PMID- 12787919
TI  - Advanced glycation endproducts as UVA photosensitizers of tryptophan and ascorbic
      acid: consequences for the lens.
AB  - Upon aging, the lens accumulates brown fluorophores, mainly derived from the
      Maillard reaction between vitamin C oxidation products and crystallins lysine
      residues. At the same time, the concentration of UVA filters decreases, allowing
      some radiation to be absorbed by lenticular advanced glycation endproducts
      (AGEs). This paper quantifies the photosensitizing activity of AGEs at various
      oxygen pressures, and compares it to that of lenticular riboflavin (RF).
      Solutions containing the sensitizer and the substrates tryptophan (Trp) and
      ascorbate (AH(-)) were irradiated at 365 nm. We show that the AGEs
      photosensitized Trp oxidation rate increases with AGEs concentration and is
      optimal at 5% oxygen, the pressure in the lens. By contrast, for AH(-), the
      photooxidation rate increases with oxygen concentration. Despite the higher
      quantum yield of RF-depending reactions, its low concentration as compared to
      that of AGEs in aging lenses induces significantly higher Trp and AH(-)
      photodegradation rates with AGEs than with RF. As ascorbate is more rapidly
      photodegraded than Trp, the antioxidant competitively protects Trp from oxidation
      up to 1 mM, although not absolutely. We conclude that in the aging lens, AH(-)
      exerts a strong UVA protecting activity, but does not impede some Trp residue to
      be photodegraded proportionally to the AGEs concentration.

PMID- 12787920
TI  - Human tissue factor pathway inhibitor-2 does not bind or inhibit activated matrix
      metalloproteinase-1.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase
      inhibitor associated with the extracellular matrices of vascular cells. A recent
      report provided in vitro evidence that TFPI-2 may be a novel inhibitor of the
      matrix metalloproteinases MMP-1, MMP-13, MMP-2 and MMP-9. In studies aimed at
      identifying the structural elements of TFPI-2 mediating the putative inhibition
      of the above MMPs, we re-examined the ability of native TFPI-2 to form complexes
      with MMP-2, MMP-9 and MMP-1, as well as assess its ability to inhibit the
      proteolytic activity of the interstitial collagenase, activated MMP-1. We report
      here that TFPI-2 failed to form complexes with MMP-2, MMP-9 and MMP-1 as revealed
      in immunoprecipitation and ligand blotting studies. In addition, TFPI-2 had no
      influence on the proteolytic activity of activated MMP-1 towards triple-helical
      collagen. These data provide presumptive evidence that TFPI-2 does not bind to
      MMP-2, MMP-9 and MMP-1, or regulate MMP-1, in the extracellular matrix.

PMID- 12787922
TI  - Effects of ultrahigh dilutions of 3,5-dichlorophenol on the luminescence of the
      bacterium Vibrio fischeri.
AB  - There is a great need for research in the field of homeopathy for laboratory test
      systems to investigate the actions of ultrahighly diluted biological effectors.
      With this in mind, we used the luminescent bacterium Vibrio fischeri, which is
      used throughout the world in testing water quality. Luminescence inhibition is
      utilized as a test parameter for the toxicity of a sample. We used ultrahigh
      dilutions (UHD) of 3,5-dichlorophenol as effector and adapted the standard test
      procedure for water toxicity in a way that let us evaluate very minute effects.
      Three groups of samples were prepared and then blinded: 45 dilutions of 3,5
      dichlorophenol in steps of 10, starting with 4.2 x 10(-2) M, with vigorous
      shaking between dilution steps; 45 identical dilutions of 3,5-dichlorophenol
      without vigorous shaking; and 49 control samples of the diluent. The results of,
      and the discussion based on, a thorough statistical analysis led to the
      conclusion that an effect based on UHD, which results in an inhibition of
      luminescence of less than 1.5%, can be confirmed for some of the potency samples.
      There were both effective and ineffective samples in the three sample groups. The
      size of the effect was very small (ca. 1.5%), though statistically significant.
      The number of effective samples was significantly higher among the vigorously
      shaken samples than among the controls and the unshaken samples (14, 6 and 7
      effective samples, respectively).

PMID- 12787921
TI  - Oxidative damage to mouse lens in culture. Protective effect of pyruvate.
AB  - Studies have been conducted to examine the feasibility of preventing oxyradical
      dependent oxidative stress to mouse lens in culture, using pyruvate as an
      antioxidant. The extent of oxidative damage to the tissue was assessed by
      measurement of the status of Na(+)-K(+) ATPase dependent active transport of
      rubidium 86Rb(+). The tissue levels of adenosine triphosphate (ATP), glutathione
      (GSH), malonaldehyde (MDA) and catalase were also determined. While the
      measurement of 86Rb(+) uptake provides an assessment of the integrity of the
      primary active transport system, measurement of the other components reflects the
      status of intracellular oxidative stress. ATP measurement also reflected on the
      overall status of metabolic integrity. Incubation of the lens with xanthine
      (XA)/xanthine oxidase (XO) system had an adverse effect on all these parameters.
      Incorporation of pyruvate was strikingly protective. The protective effect of
      pyruvate is apparently due to its ability to scavenge ROS generated in the medium
      with the possibility of its action on tissue metabolism as well. The findings are
      hence considered useful for further studies on the prevention of oxidative stress
      to tissues by exogenous supplementation with pyruvate, specially the human lens
      where the biochemistry of its antioxidant mechanisms is similar to the mouse
      lens, contrary to the rat lens.

PMID- 12787923
TI  - Degradation of (+)-catechin by Acinetobacter calcoaceticus MTC 127.
AB  - Acinetobacter calcoaceticus MTC 127 was able to grow on catechin and
      protocatechuic acid (PCA) as sole carbon source. Cells induced with catechin
      oxidized catechin and PCA at rates higher than cells of uninduced cultures. Two
      aromatic compounds, PCA and phloroglucinol carboxylic acid (PGCA) were isolated
      from culture filtrate of cells grown in catechin and characterized by infrared
      spectrometry and high performance thin-layer chromatography. Moreover, A.
      calcoaceticus MTC 127 produced high levels of PCA compared to PGCA in the
      degradation of catechin. Based upon these results, a pathway for the degradation
      of (+)-catechin in A. calcoaceticus MTC 127 is proposed. Enzymes extracted from
      catechin-induced culture showed catechin oxygenase (cox) and protocatechuate 3,4
      dioxygenase (pcd) activities. Catechin oxygenase was purified by column
      chromatography and SDS-PAGE analysis showed a single band with an apparent
      molecular weight of 47 kDa.

PMID- 12787924
TI  - Woodchuck hepatitis virus post-transcriptional regulation element enhances
      transgene expression from adenovirus vectors.
AB  - In studies of both gene therapy and gene function, transgene expression can be
      modulated at both the transcriptional and post-transcriptional levels. In a
      previous study, we optimized the transcriptional regulatory elements for
      adenovirus (Ad) vectors to mediate efficient transgene expression, including
      promoter, enhancer, intron, and poly(A) sequence. In the present study, we
      systematically investigated the ability of the Woodchuck hepatitis virus post
      transcriptional regulation element (WPRE) to enhance the expression of the
      luciferase gene, as a model gene, in the context of Ad vectors. We found that the
      WPRE in the sense orientation cloned between the luciferase gene and the poly(A)
      sequence stimulated 2- to 7-fold more luciferase expression in vitro and 2- to 50
      fold more in the liver, kidney and lung of mouse than occurred without the use of
      the WPRE. The most efficient Ad vector in this study, which contained the
      improved CMV promoter (the conventional CMV promoter with the intron A) and the
      WPRE, showed more than 700-fold luciferase expression in mouse liver than did the
      Ad vector containing the conventional CMV promoter but no WPRE. These results
      indicate that inclusion of the WPRE, combined with the optimization of
      transcriptional regulatory elements in Ad vectors, will permit a given
      therapeutic goal to be achieved with substantially fewer viral particles. This
      information would be helpful for the construction of adenovirus vectors for
      studies regarding both gene therapy and gene function.

PMID- 12787925
TI  - Glycosyltransferase expression in human colonic tissue examined by
      oligonucleotide arrays.
AB  - For an understanding of tumor-related alterations of the complex carbohydrate
      pattern of carcinomas, it is indispensable to monitor the expression profile of
      the various glycosyltransferases. The objective of this contribution was to
      perform an evaluation of the usefulness and the limits of the microarray approach
      for the identification of enzymes responsible for carbohydrate synthesis with
      differential expression in carcinomas. Expression profiles of colonic carcinomas
      were studied by oligonucleotide arrays using a novel strategy: colonic tissue of
      healthy individuals was compared with early staged colonic carcinomas; 'pure'
      cell populations were obtained by laser microdissection; RNA samples for
      hybridization with the oligonucleotide arrays were prepared by in vitro
      transcription without additional amplification. Expression of 39
      glycosyltransferases and of 10 sulfotransferases in colonic tissues was analyzed
      by Affymetrix GeneChip technology. GeneChip analysis proved the high expression
      level of ST6Gal-I, beta4Gal-TI, II and III, GalNacT-1, FT-III and showed that
      ST3Gal-IV was the most abundantly expressed enzyme in healthy tissue. The strong
      overexpression of FT-VI in healthy tissue has not been described so far, as well
      as the upregulation of FT-VIII and downregulation of GnT-I in carcinoma tissue.
      Quantitative RT-PCR confirmed that FT-VI expression was significantly enhanced in
      healthy tissue. On the other hand, GeneChip analysis failed to detect any
      expression of GnT-III and GnT-V as well as of ST3Gal-I and ST3Gal-II, although
      these sequences could be amplified from the samples used for microarray analysis.
      According to our restricted analysis of only those 39 glycosyltransferases
      present on the GeneChip U95A, alterations of sialyltransferases ST6Gal-I, ST3Gal
      IV, of fucosyltransferases FT-VI, FT-III, and probably FT-VIII, of GalNacT-I, and
      of beta4GalT-II seem to be of relevance for the aberrant biosynthesis of membrane
      bound carbohydrates during colonic carcinogenesis and metastasis.

PMID- 12787926
TI  - A new approach for studying interaction of the polygalacturonase-inhibiting
      proteins with pectins.
AB  - A method for determination of the interaction between pectins and proteins was
      developed using cross-linked polygalacturonic acid (CLPG) as the pectic substrate
      and polygalacturonase-inhibiting proteins (PGIPs). Defined water-insoluble
      pectins were prepared by chemical substitutions with acetyl or methoxyl groups on
      CLPG. In the presence of 0.1 M NaCl, PGIPs fully bound to CLPG but not to cross
      linked alginic acid (CLAL), which had a similar pK(a) to CLPG, suggesting that
      the inhibitor was not simply bound to the substrate by nonspecific electrostatic
      interaction. Optimum binding of PGIPs to CLPG occurred at pH 2.4 to 4.7. The
      binding ability of the inhibitor to CLPGs with degree of methylation (DM) of 66%
      or degree of acetylation (DAc) of 133% was not significantly changed. In
      contrast, the DM of 82% or 95% decreased the binding. These results indicated
      that the carboxylic groups of galacturonic acid residues were involved in the
      recognition of the substrate by PGIPs.

PMID- 12787927
TI  - Oxidative damage of Chinese hamster fibroblasts induced by t-butyl hydroperoxide
      and by X-rays.
AB  - The aim of this study was to investigate the mechanism(s) of X-ray-mediated cell
      damage in comparison to mechanism(s) of organic hydroperoxide cytotoxicity and to
      find the main targets for the two different kinds of cell inactivation. Damage of
      Chinese hamster fibroblasts induced by tert-butyl hydroperoxide (t-BHP) or X
      irradiation was measured by the colony-formation assay and the average single
      colony volume. DNA double-strand breaks (dsb) were determined by constant-field
      gel electrophoresis. The contents of peroxides, of SH-groups and the size of
      inactivated cells were tested for oxidative modifications.Oxidative damage of
      fibroblasts induced by t-BHP or by X-rays inhibits cell proliferation.
      Simultaneously, irradiation causes an increase of DNA dsb with the dose, while
      incubation with t-BHP yields only a very few DNA dsb. Neither chemically induced
      oxidation nor irradiation significantly changed the amount of membrane lipid
      peroxides. Oxidation with t-BHP but not irradiation leads to a loss of the
      membrane SH-groups and to an increase of cell diameter. The similar decrease of
      cell proliferation can be caused by DNA dsb without detectable membrane damage (X
      radiation) as by membrane damage with nearly no DNA dsb (chemically induced
      oxidative stress).

PMID- 12787929
TI  - Molecular cloning and characterization of cDNAs encoding hemoglobin from wheat
      (Triticum aestivum) and potato (Solanum tuberosum).
AB  - Hemoglobins (Hbs) are heme proteins encountered in all five kingdoms of living
      organisms. In plants, two different classes of Hbs have been identified:
      nonsymbiotic (class I) from both monocot and dicot species and symbiotic (class
      II) Hbs from nitrogen-fixing plants. This work reports the cloning and analysis
      of three nonsymbiotic Hb genes from wheat (Triticum aestivum) and potato (Solanum
      tuberosum). The Hb cDNAs were amplified by reverse transcriptase polymerase chain
      reaction (RT-PCR) using consensus oligonucleotide primers for nonsymbiotic Hbs.A
      wheat Hb cDNA (TaHb1) was isolated and shows a very high similarity to
      nonsymbiotic Hbs from Hordeum vulgare (98%) and Zea mays (83%). Another wheat Hb
      cDNA, designated TaHb2, exhibited strong similarity to truncated bacterial Hbs,
      the so-called 2-on-2 Hbs. In addition, a third Hb was cloned from potato, StHb.
      Expression analysis by RT-PCR demonstrated a very high expression level of the
      TaHb1 gene only in wheat roots. In contrast, the other wheat hemoglobin gene,
      TaHb2, was demonstrated to be constitutively expressed although differences in
      expression level in different tissues were observed. The expression of the TaHb1
      gene is induced in wheat roots exposed to microaerobic conditions. The potato Hb
      gene, StHb, was highly expressed in roots and also in tubers and stem tissue
      although at much reduced levels.

PMID- 12787928
TI  - Xerocomus chrysenteron lectin: identification of a new pesticidal protein.
AB  - Xerocomus chrysenteron is an edible mushroom with insecticidal properties. In an
      earlier work, we found that proteins are responsible for this toxicity. Here we
      describe the purification of a approximately 15 kDa lectin, named XCL, from the
      mushroom. Its cDNA and gDNA were cloned by PCR strategies and a recombinant form
      was expressed in Escherichia coli. Sequence alignments and sugar specificity
      showed that this protein is the third member of a new saline-soluble lectin
      family present in fungi. This protein, either purified from mushroom or expressed
      in vitro in E. coli, was found to be toxic to some insects, such as the dipteran
      Drosophila melanogaster and the hemipteran, Acyrthosiphon pisum. The lectin
      possesses a high insecticidal activity compared to lectin isolated from
      leguminosae (Lathyrus ochrus) or from the snowdrop (Galanthus nivalis).

PMID- 12787930
TI  - Quantifying molecular partition into model systems of biomembranes: an emphasis
      on optical spectroscopic methods.
AB  - Optical spectroscopies have been intensively used to determine partition
      coefficients by a plethora of methodologies. The present review is intended to
      give detailed and useful information for the determination of partition
      coefficients and addresses several relevant aspects, namely: (i) definition and
      calculation of the partition coefficient between aqueous and lipidic phases; (ii)
      partition coefficients vs. "binding" formalisms; (iii) advantages of
      spectroscopic methodologies over separation techniques; (iv) formalisms for
      various experimental approaches based on UV-Vis absorption or fluorescence
      parameters (fluorescence intensity, lifetime, anisotropy and quenching); (v)
      experimental hints, artifacts and model limitations; and (vi) a brief survey of
      nonoptical techniques.

PMID- 12787931
TI  - Polycation liposome-mediated gene transfer in vivo.
AB  - The polycation liposome (PCL), a recently developed gene transfer system, is
      simply prepared by a modification of liposomes with cetylated polyethylenimine
      (PEI), and shows remarkable transgene efficiency with low cytotoxicity. In the
      present study, we investigated the applicability of PCLs for in vivo gene
      transfer, since the PCL-mediated transgene efficiency was found to be maintained
      in the presence of serum. PCLs composed of dioleoylphosphatidylethanolamine
      (DOPE) with 5 mol% cetyl PEI (PEI average mr. wt. 1800), were superior for
      transfection to those of dipalmitoylphosphatidylcholine (DPPC) and cholesterol
      (2:1 as molar ratio) with 5 mol% cetyl PEI in vitro, although the latter PCLs
      were more efficient for gene transfer in vivo. PCL-DNA complexes were injected
      into mice via a tail or the portal vein, with the DNA being a plasmid encoding
      green fluorescent protein (GFP) or luciferase; and the expression was monitored
      qualitatively or quantitatively, respectively. Tail vein injection resulted in
      high expression of both GFP and luciferase genes in lung, and portal vein
      injection resulted in high expression of both genes in the liver. Concerning the
      gene delivery efficiency, the PCL was found to be superior to PEI or cetyl PEI
      alone. The optimal conditions for in vivo transfection with PCLs were also
      examined.

PMID- 12787932
TI  - Probing the volume changes during voltage gating of Porin 31BM channel with
      nonelectrolyte polymers.
AB  - To probe the volume changes of the voltage-dependent anion-selective channel
      (VDAC), the nonelectrolyte exclusion technique was taken because it is one of the
      few existing methods that may define quite accurately the rough geometry of lumen
      of ion channels (in membranes) for which there is no structural data.Here, we
      corroborate the data from our previous study [FEBS Lett. 416 (1997) 187] that the
      gross structural features of VDAC in its highest conductance state are asymmetric
      with respect to the plane of the membrane, and state that this asymmetry is not
      dependent on sign of voltage applied. Hence, the plasticity of VDAC does not play
      a role in the determination of lumen geometry at this state and the asymmetry is
      an internal property of the channel. We also show that the apparent diameter of
      the cis segment of the pore decreases slightly from 2 to 1.8 nm when the
      channel's conductance decreases from its high to low state. However, the trans
      funnel segment undergoes a more marked change in polymer accessible volume.
      Specifically, its larger diameter decreases from approximately 4 to 2.4 nm.
      Supposing the channel's total length is 4.6 nm, the apparent change in channel
      volume during this transition is estimated to be about 10 nm(3), i.e. about 40%
      of the channel's volume in the high conductance state.

PMID- 12787933
TI  - Temperature dependence of fluid phase endocytosis coincides with membrane
      properties of pig platelets.
AB  - In previous studies we have shown that platelets take up low molecular weight
      molecules from the medium by fluid phase endocytosis, a phenomenon that we
      previously have used to load trehalose into human platelets, after which we have
      successfully freeze-dried them. We now extend those findings to a species to be
      used in animal trials of freeze-dried platelets:pigs. Further, we report results
      of studies aimed at elucidating the mechanism of the uptake. Temperature
      dependence of fluid-phase endocytosis was determined in pig platelets, using
      lucifer yellow carbohydrazide (LY) as a marker. A biphasic curve of marker uptake
      versus temperature was obtained. The activation energy was significantly higher
      above 22 degrees C (18.7+/-1.8 kcal/mol) than below that critical temperature
      (7.5+/-1.5 kcal/mol). The activation energy of fluid phase endocytosis in human
      platelets was 24.1+/-1.6 kcal/mol above 15 degrees C. In order to establish a
      correlation between the effect of temperature on fluid phase endocytosis and the
      membrane physical state, Fourier transform infrared spectroscopy (FTIR) and
      fluorescence anisotropy experiments were conducted. FTIR studies showed that pig
      platelets exhibit a main membrane phase transition at approximately 12 degrees C,
      and two smaller transitions at 26 and 37 degrees C. Anisotropy experiments
      performed with 1,6 diphenyl-1,3,5 hexatriene (DPH) complemented FTIR results and
      showed a major transition at 8 degrees C and smaller transitions at 26 and 35
      degrees C. In order to investigate the relative roles of known participants in
      fluid phase endocytosis, the effects of several chemical inhibitors were
      investigated. LY uptake was unaffected by colchicine, methylamine, and amiloride.
      However, disruption of specific microdomains in the membrane (rafts) by methyl
      beta-cyclodextrin reduced uptake of LY by 35%. Treatment with cytochalasin B,
      which inhibits actin polymerization, reduced the uptake by 25%. We conclude that
      the inflection point in the LY uptake versus temperature plot at around 22
      degrees C is correlated with changes in membrane physical state, and that optimal
      LY internalization requires an intact cytoskeleton and intact membrane rafts.

PMID- 12787934
TI  - Molecular basis for membrane selectivity of NK-2, a potent peptide antibiotic
      derived from NK-lysin.
AB  - Increasing resistance of pathogenic bacteria against antibiotics is a severe
      problem in health care. Natural antimicrobial peptides and derivatives thereof
      have emerged as promising candidates for "new antibiotics". In contrast to
      classical antibiotics, these peptides act by direct physical destabilization of
      the target cell membrane. Nevertheless, they exhibit a high specificity for
      bacteria over mammalian cells. However, the precise mechanism of action and the
      molecular basis for membrane selectivity are still a matter of debate. We have
      designed a new peptide antibiotic (NK-2) with enhanced antimicrobial activity
      based on an effector protein of mammalian immune cells (NK-lysin). Here we
      describe the interaction of this alpha-helical synthetic peptide with membrane
      mimetic systems, designed to mimic the lipid compositions of mammalian and
      bacterial cytoplasmic membranes. Utilizing fluorescence and biosensor assays, we
      could show that on one hand, NK-2 strongly interacts with negatively charged
      membranes; on the other hand, NK-2 is able to discriminate, without the necessity
      of negative charges, between the zwitterionic phospholipids
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC), the major
      constituents of the outer leaflet of the cytoplasmic membranes of bacteria and
      mammalian cells, respectively.

PMID- 12787935
TI  - The preservation of liposomes by raffinose family oligosaccharides during drying
      is mediated by effects on fusion and lipid phase transitions.
AB  - Raffinose family oligosaccharides (RFO) have been implicated as protective agents
      in the cellular dehydration tolerance, especially of many plant seeds. However,
      their efficacy in stabilizing membranes during dehydration has never been
      systematically investigated. We have analyzed the effects of sucrose, raffinose,
      stachyose, and verbascose on liposome stability during air-drying. With
      increasing degree of polymerization (DP), the RFO were progressively better able
      to stabilize liposomes against leakage of aqueous content and against membrane
      fusion after rehydration. Indeed, there was a very tight linear correlation
      between fusion and leakage for all RFO. These data indicate that increased
      protection of liposomes against leakage with increasing DP is due to better
      protection against fusion. This is in accord with the higher glass transition
      temperature of the longer chain oligosaccharides. Further evidence for the
      influence of glass transitions on membrane stability in the dry state was
      provided by experiments testing the temperature dependence of membrane fusion.
      During incubation at temperatures up to 95 degrees C for 2 h, fusion increased
      less with temperature in the presence of higher DP sugars. This indicates that
      RFO with a higher glass transition temperature are better able to protect dry
      membranes at elevated temperatures. In addition, Fourier-transform infrared
      (FTIR) spectroscopy showed a reduction of the gel to liquid-crystalline phase
      transition temperature of dry liposomes in the presence of all investigated
      sugars. However, the RFO became slightly less effective with increasing chain
      length, again pointing to a decisive role for preventing fusion. A direct
      interaction of the RFO with the lipids was indicated by a strong effect of the
      sugars on the phosphate asymmetric stretch region of the infrared spectrum.

PMID- 12787936
TI  - Regulation of rat intestinal GLUT2 mRNA abundance by luminal and systemic
      factors.
AB  - Fructose in the lumen of the small intestine is transported across the brush
      border membrane by GLUT5, then across the basolateral membrane by GLUT2, which
      also transports glucose. Diets containing high fructose (HF) specifically enhance
      intestinal GLUT5 expression in neonatal rats, but there is little information
      concerning the dietary regulation of GLUT2 expression during early development.
      In this study, we perfused for 1-4 h 100 mM fructose, glucose (HG), alpha
      methylglucose, or mannitol solutions into the jejunum of anaesthetized 20-day-old
      rat pups. GLUT2 mRNA abundance increased only in HF- and HG-perfused intestines,
      an effect inhibited by actinomycin D but not by cycloheximide. Bypassed (Thiry
      Vella) intestinal loops were constructed, then pups were fed either HF or low
      carbohydrate diets for 5 days. GLUT2 mRNA abundance increased significantly in
      both bypassed and anastomosed intestines of Thiry-Vella pups fed HF. In contrast,
      GLUT5 mRNA abundance increased only in the anastomosed segment. In sham-operated
      pups, GLUT2 and GLUT5 mRNA abundance increased in both intestinal regions that
      corresponded to the bypassed and anastomosed regions of Thiry-Vella pups. SGLT1
      mRNA abundance was independent of diet and intestinal region in both Thiry-Vella
      and sham-operated pups. Unlike GLUT5 expression, which is regulated at the level
      of transcription only by luminal fructose, GLUT2 mRNA expression is
      transcriptionally regulated by luminal fructose and glucose as well as by
      systemic factors released during their absorption.

PMID- 12787938
TI  - The overexpression of a new ABC transporter in Leishmania is related to
      phospholipid trafficking and reduced infectivity.
AB  - This paper reports the characterization of a new ABC transporter (LtrABC1.1),
      related to the human ABCA subfamily, in the protozoan parasite Leishmania
      tropica. LtrABC1.1 is a tandem duplicated gene flanked by inverted repeats.
      LtrABC1.1 is expressed mainly in the flagellar pocket of the parasite. Drug
      resistance studies in Leishmania overexpressing LtrABC1.1 showed the transporter
      not to confer resistance to a range of unrelated drugs. LtrABC1.1 appears to be
      involved in lipid movements across the plasma membrane of the parasite since
      overexpression reduces the accumulation of fluorescent phospholipid analogues.
      The activity of this protein may also affect membrane movement processes since
      secreted acid phosphatase (SAP) activity was significantly lower in promastigotes
      overexpressing LtrABC1.1. In vitro infection experiments with macrophages
      indicated LtrABC1.1-transfected parasites to be significantly less infective.
      Together, these results suggest that this new ABC transporter could play a role
      in lipid movements across the plasma membrane, and that its activity might
      influence vesicle trafficking. This is the first ABCA-like transporter described
      in unicellular eukaryotes.

PMID- 12787939
TI  - Physicochemical characterization of silicon-containing glycolipids by DSC, FT
      Raman spectroscopy and X-ray diffraction.
AB  - Derivatives of dimethylalkylchlorosilanes are novel substances which may be used
      in formulations for drug targeting. In order to design their properties it is
      essential to perform physicochemical characterization. For this purpose, a
      combination of differential scanning calorimetry (DSC), FT-Raman spectroscopy and
      X-ray diffraction is well suited. For the starting material
      dimethyloctadecylchlorosilane (DMOC), the assignment of Raman bands is discussed.
      The influence of sugar-containing head groups on the structures of the
      hydrocarbon chains of 1-O-(dimethyldodecylsilyl)-[2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranoside] and 1-O-(dimethyloctadecylsilyl)-[2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranoside] was investigated using the band position of the symmetric
      methylene mode. The temperature dependence of conformationally sensitive bands in
      the CH(2)-stretching region (2800-2900 cm(-1)), C-C-stretching region (1000-1150
      cm(-1)) and CH(3)-rocking region (830-900 cm(-1)) was studied to characterize the
      state of order of the alkyl chains. Using X-ray diffraction, the repeating
      distances of layered structures was determined. The phase transitions occurring
      were found to be completely reversible. The subcell of DMOC shows an orthorhombic
      perpendicular packing structure in the crystalline state.

PMID- 12787937
TI  - An association of 27- and 40-kDa molecules with glycolipids that bind A-B
      bacterial enterotoxins to cultured cells.
AB  - It is well recognized that the Shiga-like toxins (Stxs) preferentially bind to
      Gb3 glycolipids and the cholera toxin (CT) and heat-labile enterotoxin (LTp) bind
      to GM1 gangliosides. After binding to the cell surface, A-B bacterial
      enterotoxins have to be internalized by endocytosis. The transport of the toxin
      glycolipid complex has been documented in several manners but the actual
      mechanisms are yet to be clarified. We applied a heterobifunctional cross-linker,
      sulfosuccinimidyl-2-(p-azidosalicylamido)-1,3'-dithiopropionate (SASD), to detect
      the membrane proteins involved in the binding and the transport of A-B bacterial
      enterotoxins in cultured cells. Both Stx1 and Stx2 bound to the detergent
      insoluble microdomain (DIM) of Vero cells and Caco-2 cells, which were
      susceptible to the toxin, but neither was bound to insusceptible CHO-K1 cells.
      Both CT and LTp bound to the DIM of Vero cells, Caco-2 cells, and CHO-K1 cells.
      In a cross-linking experiment, Stx1 cross-linked only with a 27-kDa molecule,
      while Stx2, which was more potently toxic than Stx1, cross-linked with 27- and 40
      kDa molecules of Vero cells as well as of Caco-2 cells; moreover, no molecules
      were cross-linked with the insusceptible CHO-K1 cells. LTp was cross-linked only
      to the 27-kDa molecule of these three cell types but the CT, which was more toxic
      than LTp, was also cross-linked with 27- and 40-kDa molecules of Vero cells, Caco
      2 cells, and CHO-K1 cells. The 27- and the 40-kDa molecules might play a role in
      the endocytosis and retrograde transport of A-B bacterial enterotoxins.

PMID- 12787940
TI  - Influence of the temperature in the adsorption of sodium dodecyl sulfate on
      phosphatidylcholine liposomes.
AB  - The influence of the temperature on the adsorption of monomeric and micellar
      solutions of the anionic surfactant sodium dodecyl sulfate (SDS) on
      phosphatidylcholine (PC) liposomes was investigated using the fluorescent probe 2
      (p-toluidinyl)-naphthalene-6-sodium sulfonate (TNS). The number of adsorbed
      molecules was quantified by measuring changes in the electrostatic potential
      (Psi(o)) of the liposomes/probe during an incubation with SDS at varying
      temperatures. At low surfactant concentrations (from 0.05 to 0.25 mM), the
      increase in temperature reduced the number of surfactant molecules incorporated
      per vesicle regardless of the incubation time, whereas at high surfactant
      concentrations (from 0.50 to 1.0 mM) the incubation time has an opposite effect
      on this process. Thus, after 10s, the surfactant adsorption decreased with
      temperature, yet it increased progressively with time. The adsorption was linear
      with temperature below critical micellar concentration (CMC) of SDS and this
      linear tendency did not change above CMC. This suggests an adsorption of SDS
      monomers regardless of the surfactant concentration.

PMID- 12787941
TI  - Activity and location of olive oil phenolic antioxidants in liposomes.
AB  - The antioxidant activity of hydroxytyrosol, hydroxytyrosol acetate, oleuropein,
      3,4-dihydroxyphenylelenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylelenolic
      acid dialdehyde (3,4-DHPEA-EDA) towards oxidation initiated by 2,2'-azobis(2
      amidinopropane) hydrochloride in a soybean phospholipid liposome system was
      studied. The antioxidant activity of these olive oil phenols was similar and the
      duration of the lag phase was almost twice that of alpha-tocopherol. Trolox, a
      water-soluble analogue of alpha-tocopherol, showed the worst antioxidant
      activity. However, oxidation before the end of the lag phase was inhibited less
      effectively by the olive oil phenols than by alpha-tocopherol and Trolox.
      Synergistic effects (11-20% increase in lag phase) were observed in the
      antioxidant activity of combinations of alpha-tocopherol with olive oil phenols
      both with and without ascorbic acid. Fluorescence anisotropy of probes and
      fluorescence quenching studies showed that the olive oil phenols did not
      penetrate into the membrane, but their effectiveness as antioxidants showed they
      were associated with the surface of the phospholipid bilayer.

PMID- 12787942
TI  - Cutinase-AOT interactions in reverse micelles: the effect of 1-hexanol.
AB  - Cutinase encapsulated in dioctyl sulfosuccinate reverse micelles displays very
      low stability, undergoing fast denaturation due to an anchoring at the micellar
      interface. The denaturation process and the structure of the reverse micelle were
      characterized using biophysical techniques. The kinetics of denaturation observed
      from fluorescence match the increase of the hydrodynamic radius of reverse
      micelles. Denaturation in reverse micelles is mainly the unfolding of the three
      dimensional structure since the decrease in the circular dichroism ellipticity in
      the far-UV range is very small. The process is accompanied by an increase in the
      steady-state anisotropy, as opposed to what happens for denaturation in aqueous
      solution. Since 1-hexanol used as co-surfactant in dioctyl sulfosuccinate reverse
      micelles slows or even prevents cutinase denaturation, its effect on cutinase
      conformation and on the size of reverse micelles was analyzed. When 1-hexanol is
      present, cutinase is encapsulated in a large reverse micelle, as deduced from
      dynamic light scattering. The large reverse micelle filled with cutinase was
      built from the fusion of reverse micelles according to a pseudo-unimolecular
      process ranging in time from a few minutes to 2h depending on the reverse
      micellar concentration. This slow equilibrium driven by the encapsulated cutinase
      has not been reported previously. The encapsulation of cutinase in dioctyl
      sulfosuccinate reverse micelles establishes a completely new equilibrium
      characterized by a bimodal population of empty and filled reverse micelles, whose
      characteristics depend greatly on the interfacial characteristics, that is, on
      the absence or presence of 1-hexanol.

PMID- 12787943
TI  - In vitro lipofection with novel series of symmetric 1,3-dialkoylamidopropane
      based cationic surfactants containing single primary and tertiary amine polar
      head groups.
AB  - A novel series of symmetric double-chained primary and tertiary 1,3-dialkoylamido
      monovalent cationic lipids were synthesized and evaluated for their transfection
      activities. In the absence of the helper lipid DOPE (1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine), only the primary and tertiary dioleoyl derivatives 1,3lmp5
      and 1,3lmt5, respectively elicited transfection activity. This is a striking
      difference between symmetrical 1,2-diacyl glycerol-based monovalent cationic
      lipids that always found both dioleoyl and dimyristoyl analogues being efficient
      transfection reagents. In the presence of helper lipid, all cationic derivatives
      induced marker gene expression, except the dilauroyl analogues 1,3lmp1 and
      1,3lmt1 that elicited no transfection activity. Combining electrophoretic
      mobility data of the lipoplexes at different charge ratios with transfection
      activity suggested two requirements for high transfection activity with
      monovalent double-chained cationic lipids, that is, binding/association of the
      lipid to the plasmid DNA and membrane fusion properties of the lipid layers
      surrounding the DNA.

PMID- 12787944
TI  - The first total synthesis of the marine fatty acid (+/-)-9-methoxypentadecanoic
      acid: a synthetic route towards mid-chain methoxylated fatty acids.
AB  - The marine fatty acid (+/-)-9-methoxypentadecanoic acid was synthesized for the
      first time in seven steps (7.8% overall yield) starting from commercially
      available 9-decen-1-ol. The key step in the synthesis was the coupling of
      pentylmagnesium bromide with 1-benzyloxy-9,10-epoxydecane under 1,5
      cyclooctadiene copper (I) chloride catalysis. Nuclear magnetic resonance data are
      provided for the first time for this type of methoxylated fatty acids and the
      synthetic approach utilized is of general applicability since it can be used in
      the synthesis of other mid-chain methoxylated fatty acids. This synthetic
      methodology should afford sufficient quantities of these fatty acids for
      biological evaluation. The spectral data obtained for the title compound will
      also be helpful in subsequent characterizations of other mid-chain methoxylated
      fatty acids using nuclear magnetic resonance spectroscopy.

PMID- 12787945
TI  - DMPG gel-fluid thermal transition monitored by a phospholipid spin labeled at the
      acyl chain end.
AB  - Low ionic strength aqueous dispersion of dimyristoyl phosphatidylglycerol (DMPG)
      presents a rather peculiar gel-fluid thermal transition behavior. The lipid main
      phase transition occurs over a large temperature interval (ca. 17 degrees C),
      along which several calorimetric peaks are observed. Using lipids spin labeled at
      the acyl chain end, a two-peak electron spin resonance (ESR) spectrum is observed
      along that temperature transition region (named intermediate phase), at three
      different microwave frequencies: L-, X- and Q-bands. The intermediate phase ESR
      spectra are analyzed, and shown to be most likely due to spin labels probing two
      distinct types of lipid organization in the DMPG bilayer. Based on the ESR
      spectra parameters, a model for the DMPG intermediate phase is proposed, where
      rather fluid and hydrated domains, possibly high curvature regions, coexist with
      patches that are more rigid and hydrophobic.

PMID- 12787946
TI  - The toxicological potential of khat.

PMID- 12787947
TI  - Effect of Catha edulis (khat) chewing on plasma lipid peroxidation.
AB  - The effect of regular khat (Catha edulis) chewing and the combination of khat
      chewing and smoking on plasma lipid peroxidation as a biomarker of oxidative
      stress and free radical activity (measured as plasma malondialdehyde, MDA), as
      well as on the lipid profiles were investigated. The fasting plasma levels of MDA
      were non-significantly higher in both groups (4% in khat chewers and 9.2% in khat
      chewers and smokers), whereas these levels were observed to be significantly
      increased at post meal and 2h through the khat session. Post meal increase of
      plasma MDA could be attributed partially to the meal-induced oxidative stress and
      the possible decrease in the overall antioxidant capacity. This increase in
      plasma levels of MDA in both tested groups were found to be higher in the control
      group suggesting the presence of other contributing factors beside the meal
      induced oxidative stress. Plasma levels of MDA were observed to fall slightly 2h
      through the khat session over the post meal levels, suggesting a lack of additive
      effect of khat consumption. Plasma triglycerides, total cholesterol, and LDL
      cholesterol were shown to be non-significantly affected in this study by khat
      chewing or by the combination of khat chewing and smoking.

PMID- 12787948
TI  - Evaluation of antipyretic potential of Cleome viscosa Linn. (Capparidaceae)
      extract in rats.
AB  - The antipyretic activity of a methanol extract of Cleome viscosa Linn. (CVME) was
      investigated for its potential on normal body temperature and yeast-induced
      pyrexia in albino rats. The CVME, at doses of 200, 300, and 400mg/kg BW p.o.,
      showed significant reduction in normal body temperature and yeast-provoked
      elevated temperature in a dose-dependent manner. The effect also extended upto 5h
      after the drug administration. The anti-pyretic effect of CVME was comparable to
      that of paracetamol (150mg/kg p.o.), a standard anti-pyretic agent.

PMID- 12787949
TI  - Traditional herbal drugs of southern Uganda. Part III: isolation and methods for
      physical characterization of bioactive alkanols from Rubus apetalus.
AB  - The East African plant Rubus apetalus Poir. was collected as a component of an
      ethnobotanical survey in southern Uganda. No phytochemical investigations of this
      plant have been found in the literature. Preliminary antimicrobial susceptibility
      tests performed in Uganda indicated biological activity against several bacterial
      and one fungal human pathogen. Bulk re-collection of Rubus apetalus was
      accomplished and crude extraction performed in preparation for further testing.
      Two chemical fractions of the crude extract were active in the antimicrobial
      susceptibility assay. Fractionation of one of the active crude fractions led to
      the isolation and elucidation of a mixture of related compounds that exhibit
      antimicrobial activity against Staphylococcus aureus (MIC=62 microg/ml),
      Streptococcus faecalis (16 microg/ml) and Candida albicans (32 microg/ml).

PMID- 12787950
TI  - Effect of the desert plant Retama raetam on glycaemia in normal and
      streptozotocin-induced diabetic rats.
AB  - The effect of the aqueous extract of Retama raetam (RR) on blood glucose levels
      was investigated in fasting normal and streptozotocin-induced diabetic rats after
      single and repeated oral administration. The aqueous extract of RR at a dose of
      20mg/kg significantly reduced the blood glucose in normal rats 6h after a single
      oral administration (P<0.005) and two weeks after repeated oral administration
      (P<0.05). This hypoglycaemic effect is more pronounced in streptozotocin (STZ)
      diabetic rats (P<0.001). The aqueous extract of RR had no effect on basal plasma
      insulin levels indicating that the underlying mechanism of RR activity is extra
      pancreatic. These findings suggest that the aqueous extract of RR possess
      significant hypoglycaemic effect in both normal and STZ diabetic rats.

PMID- 12787951
TI  - Effects of Cyperus articulatus compared to effects of anticonvulsant compounds on
      the cortical wedge.
AB  - Cyperus articulatus L. (Cyperaceae) is a plant commonly used in traditional
      medicine in Africa and Latin America to treat many diseases. The water extract
      from rhizomes of Cyperus articulatus concentration-dependently reduced
      spontaneous epileptiform discharges and NMDA-induced depolarisations in the rat
      cortical wedge preparation at concentrations at which AMPA-induced
      depolarisations are not affected. The two antiepileptic compounds, valproate and
      ethosuximide, possessed effect neither on epileptiform discharges nor on AMPA-
      and NMDA-induced depolarisations. Phenobarbital, pentobarbital and phenythoin
      inhibited both AMPA- and NMDA-induced depolarisations and spontaneous
      epileptiform discharges. The effects of Cyperus articulatus were very close to
      the effect of D-CPPene. D-CPPene also inhibited spontaneous epileptiform
      discharges and antagonised NMDA- but not AMPA-induced depolarisations. The
      extract of Cyperus articulatus could contain components acting as NMDA
      antagonists.

PMID- 12787953
TI  - Cholesterol-lowering activity of the aqueous extract of Spergularia purpurea in
      normal and recent-onset diabetic rats.
AB  - The purpose of this study was to examine the effect of single and repeated oral
      administration of the aqueous extract of Spergularia purpurea (SP) at a dose of
      10mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the
      aqueous extract of SP induced a significant decrease of the plasma cholesterol
      concentrations 6h after a single oral administration (P<0.05) and 2 weeks after
      repeated oral administration (P<0.05). The plasma triglycerides levels increased
      significantly 6h after a single oral administration (P<0.05) and decreased 2
      weeks after repeated oral administration (P<0.05). In diabetic rats, SP treatment
      caused a significant decrease of plasma cholesterol levels after a single
      (P<0.01) and repeated (P<0.01) oral administration. A significant increase of
      triglycerides levels was observed 6h after a single oral administration of the SP
      aqueous extract (P<0.01). One week after repeated oral administration of SP
      aqueous extract, the plasma triglycerides levels were significantly decreased
      (P<0.005) and still dropped after 2 weeks (P<0.01). On the other hand, the
      repeated oral administration of SP aqueous extract caused a significant decrease
      of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic
      (P<0.01) rats. We conclude that the aqueous extract of SP exhibits a cholesterol
      and body weight-lowering activities in both normal and severe hyperglycaemic
      rats.

PMID- 12787952
TI  - Antibacterial and anti-inflammatory activities of some plants used for medicinal
      purposes in Kenya.
AB  - Aqueous, hexane and methanol extracts of 12 plant species, traditionally used in
      Kenya for treatment of ailments of infectious and/or inflammatory nature were
      screened for in vitro antibacterial and anti-inflammatory activities.
      Antibacterial activity was tested using the agar diffusion method while anti
      inflammatory activity was tested using the cyclooxygenase (COX-1) assay. All the
      antibacterial activity was against Gram-positive bacteria with nine plant species
      showing some activity against Staphylococcus aureus. The highest activity was
      found in the methanol extracts of Maytenus senegalensis, Plectranthus barbatus,
      Zanthoxylum chalybeum, Zanthoxylum usambarense and hexane extracts of Spiranthes
      mauritianum. All the plant species showed some anti-inflammatory activities. In
      most cases, methanol extracts caused higher inhibition than aqueous and hexane
      extracts.

PMID- 12787954
TI  - Native Americans' choice of species for medicinal use is dependent on plant
      family: confirmation with meta-significance analysis.
AB  - We test the hypothesis that the choice by traditional people of species of plants
      for medicinal use does or does not depend on the families to which those species
      belong. Our geographic context is continental North America north of the Rio
      Grande River. Our plant context is flowering plants. Our ethnological context is
      Native American traditions. Our null hypothesis is that the probability of any
      species being medicinal is the fraction of all species that are medicinal, no
      matter the family to which that species may belong. Classical statistical
      techniques and the experience of ethnobiologists had already made it clear that
      among very large plant families, most have either very many or very few medicinal
      species. Here we use intense computation to simulate thousands of data sets to
      create predictions to compare with the observed data for medium and small
      families. Our results clearly show that a surprising number of medium and small
      families also have very many or very few medicinal species. Recent molecular,
      fossil and cytological studies have confirmed the evolutionary naturalness of
      most plant families. This suggests that species in the same family may have
      inherited from common ancestors similar ecological adaptations, such as ways to
      protect themselves from herbivores, pathogens or decomposers. Some of these
      adaptations affect the physiology of the attacking organisms, suggesting an
      explanation for the clear preferences of Native American traditions to choose
      medicinal species from some families much more than from others, regardless of
      the size of those families.

PMID- 12787955
TI  - Evaluation of antimicrobial activities of Satureja hortensis L.
AB  - The present study was designated to evaluate the antimicrobial activities of
      methonol and hexane extracts of Satureja hortensis L. which is an annual herb
      used as traditional folk medicine in Eastern Anatolia region of Turkey for the
      treatment of different infectious diseases and disorders. The antimicrobial
      activities of the extracts against 147 laboratory strains belong to 55 bacterial
      species, and 31 isolates of 1 yeast and 4 fungi species were tested by using disc
      diffusion assay. The results showed that hexane extract of Satureja hortensis had
      no antifungal, but antibacterial activity against four strains of three Bacillus
      species whereas methanol extract of Satureja hortensis had both anticandidal and
      antibacterial effects. It inhibited the growth of 23 strains of 11 bacterial
      species and 6 isolates of Candida albicans, at the concentration of 300microg/ml.
      Satureja hortensis did not show antimicrobial activity against the remaining
      microorganisms (83%) tested including most and all of the clinic and plant
      pathogenic microorganisms, respectively. Methanol extract showed stronger and
      broader spectrum of antimicrobial activity as compared to hexane extract.

PMID- 12787956
TI  - Antioxidant activity of prenylated flavonoids from the West African medicinal
      plant Dorstenia mannii.
AB  - The antioxidant activities of three prenylated flavonoids from Dorstenia mannii
      (6,8-diprenyleriodictyol, dorsmanin C and dorsmanin F) were compared to the
      common, non-prenylated flavonoid, quercetin. The prenylated flavonoids were found
      to be potent scavengers of the stable free radical 1,1-diphenyl-2-picrylhydrazyl
      (DPPH), and are more potent than butylated hydroxy toluene (BHT), a common
      antioxidant used as a food additive. The prenylated flavonoids also inhibited
      Cu(2+)-mediated oxidation of human low density lipoprotein (LDL). Dose-response
      studies indicated that the prenylated flavonoids were effective inhibitors of
      lipoprotein oxidation with IC50 values <1 microM and had similar inhibitory
      potency compared to quercetin, but was not directly related to Cu binding. Unlike
      quercetin, they did not show any pro-oxidant activity at high doses in the Cu(2+)
      mediated lipoprotein oxidation system. The medicinal action of Dorstenia mannii
      may be related to the high concentration of potent antioxidant prenylated
      flavonoids in this species.

PMID- 12787957
TI  - Isolation and characterization of antioxidant phenolic compounds from the aerial
      parts of Hypericum hyssopifolium L. by activity-guided fractionation.
AB  - Dried methanol extract of Hypericum hyssopifolium subsp. elongatum var. elongatum
      was dissolved in distilled water, and then fractioned by re-extracting with
      petroleum ether, chloroform, and ethyl acetate, subsequently. Antioxidant and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities of these fractions
      were determined, in vitro. The amounts of total phenolic compounds were also
      determined. None of these fractions showed antioxidant activity, in contrast
      water and ethyl acetate fractions acted as prooxidant. However, the ethyl acetate
      fraction exhibited the highest DPPH radical-scavenging activity and the amount of
      its total phenolic compound was highest, too. Therefore, ethyl acetate fraction
      was subjected to further separation by chromatographic methods. Thus, five
      flavonoids (I3,II8-biapigenin, quercetin, quercetin-3-O-alpha-L
      arabinofuranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-beta-D
      galactopyranoside-7-O-beta-D-glucopyranoside) and a napthodianthrone (hypericin)
      were isolated, and their structures were determined by UV, IR, NMR, and MS
      spectroscopic methods. All isolated compounds showed antioxidant and DPPH radical
      scavenging activities. Although, I3,II8-biapigenin and hypericin were able to
      show highest antioxidant activity, they had the lowest DPPH radical-scavenging
      activities. From these results, it can be suggested that these compounds may be
      used as potential antioxidants. In addition, the petroleum ether fraction was
      subjected to silica gel column chromatography (CC). Then, n-dotriacontanyl
      hexadecanoate, bis(2-methylheptyl) phthalate, and beta-sitosterol were isolated
      from it. It is of interest to present the spectral data of bis(2-methylheptyl)
      phthalate first time in the present study.

PMID- 12787958
TI  - Antifungal activities of nine traditional Mexican medicinal plants.
AB  - Eighteen plant extracts from nine traditional Mexican medicinal plants were
      tested for antifungal activity against two dermatophyte fungal species
      (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte
      (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was
      manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum
      oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and
      Annona cherimolia.

PMID- 12787959
TI  - The in vitro effects of Hypericum species on human leukocyte myeloperoxidase
      activity.
AB  - Myeloperoxidase (MPO) is a major component of the antimicrobial system of
      polymorphonuclear neutrophils. The heme enzyme MPO catalyzes the conversion of
      hydrogen peroxide and chloride to hypochlorous acid. Hypochlorous acid is the
      major strong oxidant produced by neutrophils and may contribute to inflammatory
      tissue damage. It was reported that certain antiinflammatory drugs are capable of
      inhibiting MPO activity and this inhibition may account for their
      antiinflammatory effect. Hypericum L. is a genus of about 400 species, widespread
      throughout the world. Some species of genus exhibit a significant
      antiinflammatory activity beside their several pharmacological properties such as
      antidepressant, diuretic, antihelmintic, and antibacterial. In this study, we
      investigated the in vitro effects of three Hypericum species, which exhibit
      antiinflammatory activity, on human polymorphonuclear leukocyte MPO activity. We
      found that each extract of Hypericum species reduced the peroxidative and
      chlorinating activity of human leukocyte MPO in concentration-dependent manner.
      The antiinflammatory activity of these species may be related with inhibition of
      MPO activity.

PMID- 12787960
TI  - Propolis: lymphocyte proliferation and IFN-gamma production.
AB  - We evaluated propolis influence on polyclonal activation of lymphocytes by
      concanavalin A (Con A). The in vitro experiments showed that propolis decreases
      splenocyte proliferation both in the absence or presence of Con A. The
      suppression in mitogen-induced splenocyte proliferation also occurred when mice
      were treated intraperitoneally with propolis for 3 days. An increased of IFN
      gamma production in the culture supernatants of the same cells was observed. A
      dual action of propolis on lymphocyte activation was proposed: it decreases
      splenocyte proliferation in the presence or absence of Con A and stimulates IFN
      gamma production by spleen cells. These results are important to understand the
      immunomodulatory action of propolis on the host's specific and non-specific
      immunity.

PMID- 12787961
TI  - Antimicrobial and antiproliferative activity of Peucedanum nebrodense (Guss.)
      Strohl.
AB  - Acetone extract of Peucedanum nebrodense (Guss.) Strohl., a rare endemic species
      from the Madonie mountains (Sicily), was tested in vitro for its antimicrobial
      activity against bacterial reference strains and antiproliferative activity
      against K562 (human chronic myelogenous leukemia), HL-60 (human leukemia) and
      L1210 (murine leukemia) cell lines. The acetone extract showed antiproliferative
      IC50 values in the range of 14-0.27 microg/ml.

PMID- 12787962
TI  - Screening of anti-bacterial activity of medicinal plants from Belize (Central
      America).
AB  - Twenty-one extracts from seven herbal drugs, Aristolochia trilobata
      (Aristolochiaceae) leaves and bark, Bursera simaruba (Burseraceae) bark, Guazuma
      ulmifolia (Sterculiaceae) bark, Hamelia patens (Rubiaceae) leaves and Syngonium
      podophyllum (Araceae) leaves and bark, used in traditional medicine of Belize
      (Central America) as deep and superficial wound healers, were evaluated for their
      anti-bacterial properties. Activity was tested against standard strains of
      Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus
      aureus ATCC 25923 and Enterococcus faecalis ATCC 29212. Almost all the extracts
      were able to inhibit the growth of one or more of the bacterial strains, except
      that of Enterococcus faecalis. For the first time an anti-microbial activity is
      reported for Aristolochia trilobata as well as for Syngonium podophyllum. The
      hexane extracts of Aristolochia trilobata leaves and bark were the most active
      extracts against Staphylococcus aureus (MIC=0.31 and 0.625mg/ml, respectively).

PMID- 12787963
TI  - Evaluation of Tanacetum larvatum for an anti-inflammatory activity and for the
      protection against indomethacin-induced ulcerogenesis in rats.
AB  - Oral administration of the chloroform extract from Tanacetum larvatum (Griseb. ex
      Pant.) Kanitz caused a dose-dependent anti-inflammatory effect in the carrageenan
      induced rat paw oedema test. The obtained anti-inflammatory effect was 8.6, 32.8,
      37.0 and 49.5% for the extract doses of 25, 50, 100 and 200mg/kg, respectively,
      being statistically significant at a dose of 50mg/kg. Indomethacin had a strong
      anti-inflammatory effect of 73.4% at a dose of 8mg/kg, but large gastric lesions
      were detected. When the plant extract in the highest tested dose (200mg/kg) was
      concomitantly given with indomethacin, the anti-inflammatory effect was slightly
      enhanced, but the gastric lesions were significantly reduced. The anti
      inflammatory and anti-ulcer activity may be mainly due to the inhibition of DNA
      binding of the transcription factor NF-kappaB by components of the plant extract.
      This was proven in an electrophoretic mobility shift assay at a concentration of
      50microg/ml. Due to its anti-inflammatory as well as anti-ulcer effects,
      Tanacetum larvatum should especially be used combined with those drugs that are
      known both for their strong anti-inflammatory activities and the ulcerogenic side
      effects such as NSAIDs.

PMID- 12787964
TI  - Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia
      speciosa leaves in Type II diabetics. A dose-dependence study.
AB  - The antidiabetic activity of an extract from the leaves of Lagerstroemia speciosa
      standardized to 1% corosolic acid (Glucosol) has been demonstrated in a
      randomized clinical trial involving Type II diabetics (non-insulin-dependent
      diabetes mellitus, NIDDM). Subjects received a daily oral dose of Glucosol and
      blood glucose levels were measured. Glucosol at daily dosages of 32 and 48mg for
      2 weeks showed a significant reduction in the blood glucose levels. Glucosol in a
      soft gel capsule formulation showed a 30% decrease in blood glucose levels
      compared to a 20% drop seen with dry-powder filled hard gelatin capsule
      formulation (P<0.001), suggesting that the soft gel formulation has a better
      bioavailability than a dry-powder formulation.

PMID- 12787966
TI  - Estrogen replacement therapy and frontotemporal dementia.
AB  - OBJECTIVE: To examine the relationship between estrogen replacement therapy (ERT)
      and frontotemporal dementia (FTD). METHODS: We examined the files of thirty
      female patients diagnosed with FTD at the University of California, San Francisco
      (UCSF)-Alzheimer's Disease Research Center in Fresno between the years of 1994
      and 1999. Twenty-one patients (70%) were found to have been taking ERT at the
      time of their evaluation. This was compared with an estimate of estrogen use in a
      similar cohort from the general population (24%). RESULTS: Chi-square (chi(2))
      analysis found this number to be significantly greater than estimates from the
      general population significant (chi(2)[df=1, N=30]=34.803, P<0.01). CONCLUSIONS:
      Three potential explanations for the findings are put forth, including an
      intriguing neurobiological relationship between estradiol and tau, the complex
      protein implicated in the etiology of FTD.

PMID- 12787967
TI  - Associations with menopause and menopausal transition in a nationally
      representative US sample.
AB  - OBJECTIVES: The purpose of this study was to assess sociodemographic and
      behavioral factors in relation to menopausal status in a representative sample of
      the United States population. METHODS: Data were taken from the 1999 National
      Health Interview Survey (NHIS), limited to women aged 40-54 years who had not
      undergone surgical menopause. Menopausal transition was defined as absence of
      menstrual cycles for at least 3 but no more than 11 months or cycles that had
      become irregular in the past 12 months. Postmenopause was defined as absence of a
      menstrual cycle for 12 or more months. We used age-adjusted three-level logistic
      regression to examine the association between menopausal status and smoking,
      race/ethnicity, education, body mass index, exercise, and alcohol use. RESULTS:
      Twenty percent of women in this sample had experienced natural menopause, 18%
      were in the menopausal transition and 61% were premenopausal. Using premenopause
      as the reference group, current cigarette smoking was strongly associated with
      being postmenopausal (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.7, 3.0)
      and weakly associated with being in the menopausal transition (OR 1.4, 95% CI
      1.1, 1.8). Education level was associated with being postmenopausal (OR 0.4, 95%
      CI 0.3, 0.6 comparing women with a college degree to women who had not completed
      high school), and alcohol use was weakly associated with being postmenopausal,
      with no evidence of a dose-response. CONCLUSIONS: The associations with smoking
      were stronger for postmenopause than for the transition phase, suggesting that
      the effect of smoking may be to shorten the transition period. Education level
      may be a marker for other exposures that affect ovarian senescence.

PMID- 12787968
TI  - Climacteric symptoms and knowledge about hormone replacement therapy among Hong
      Kong Chinese women aged 40-60 years.
AB  - OBJECTIVES: To evaluate the use of hormone replacement therapy (HRT), the
      prevalence of climacteric symptoms, and the knowledge about HRT. METHODS: A
      prospective study was conducted by telephone interview among a randomly selected
      population-based sample of 978 Hong Kong Chinese women aged 40-60 years. RESULTS:
      Of 414 women with a history of either natural or surgical menopause, 22 (5.3%)
      and 17 (4.1%), respectively, were either past or current users of HRT. The
      climacteric symptom scores of premenopausal women were significantly lower than
      those of perimenopausal women, but were comparable with those of postmenopausal
      women. The commonest climacteric symptom was 'muscle and joint pains' which was
      reported in 553 (56.6%) women, while only 228 (23.3%) and 151 (15.4%) women
      reported hot flushes and night sweating, respectively. Moreover, only 230 (23.5%)
      women realized that HRT could relieve menopausal symptoms and only 33 (3.4%)
      women were aware that HRT was protective against osteoporosis. In general, women
      with more climacteric symptoms, who had ever used HRT, and those with higher
      education level and higher family income, had better knowledge about HRT.
      CONCLUSIONS: Postmenopausal Hong Kong Chinese women have a low HRT usage rate and
      the majority of them are lacking of the knowledge about HRT.

PMID- 12787969
TI  - The effect of various regimens of hormone replacement therapy on mammographic
      breast density.
AB  - OBJECTIVES: To evaluate the effect of three distinct hormone replacement therapy
      regimens on mammography. METHODS: 121 postmenopausal women who had never received
      or were past users of hormone replacement therapy were studied prospectively.
      Women with an intact uterus were randomly allocated either to conjugated equine
      estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=34) or to
      17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E(2)/NETA, n=35).
      Hysterectomized women received CEE 0.625 mg (CEE, n=25). Women who either
      declined or did not qualify for treatment served as controls (n=27). Treatment
      was continuous and the study period lasted 12 months. Main outcome measures were
      the changes according to Wolfe classification between baseline and 12-month
      mammograms. RESULTS: No increase in breast density was identified in any of the
      women in the control group. Two women (8%) in the CEE group showed an increase in
      breast density. Four women (11.8%) in the CEE/MPA and 11 women (31.4%) in the
      E(2)/NETA group revealed an increase in breast density. No woman in the therapy
      groups showed an involution of fibroglandular tissue while seven women (25.9%) in
      the control group exhibited involution of breast parenchyma. CONCLUSIONS: Our
      study suggests that hormone replacement therapy may suspend breast involution but
      does not increase breast density in the majority of patients. In the minority of
      patients who show a density increase, the magnitude of this increase varies
      according to the regimen employed.

PMID- 12787970
TI  - Prevention of postmenopausal bone loss with exchange for short-term HRT for
      1alpha-hydroxycholecalciferol.
AB  - OBJECTIVE: The present study investigated bone turnover with exchange of hormone
      replacement therapy (HRT) by treatment with 1alpha-hydroxycholecalciferol in
      early postmenopausal women. METHODS: Subjects included a total of 75
      postmenopausal women between 49 and 59 years of age who visited the Department of
      Obstetrics and Gynecology at Osaka Medical College Hospital for regular
      gynecological checkups and menopausal disorder, postmenopausal osteoporosis or
      hyperlipidemia, and were diagnosed with menopausal disorder or osteopenia.
      Changes in bone turnover and vertebral bone mineral density (BMD) in 28 patients
      who had undergone HRT; conjugated equine estrogen 0.625 mg daily and
      medroxyprogesterone acetate 2.5 mg daily) for at least 2 years and then switched
      to 1alpha-hydroxycholecalciferol (0.5 microg orally twice daily) and in 26
      patients who were observed without drug administration after discontinuation of
      HRT were compared with those in 37 patients who continued HRT. BMD of the lumbar
      spine (L2-4) was determined using Dual Energy X-ray Absorptiometry. RESULTS:
      While we observed a significant decrease in vertebral bone mass in the HRT-no
      medication group at 12 months (P=0.049) and 18 months (P=0.013), there was no
      significant decrease in vertebral bone mass in either the continuous HRT group or
      the group with change of HRT to 1alpha-hydroxycholecalciferol. In the group with
      change of HRT to 1alpha-hydroxycholecalciferol, although urinary pyridinoline
      level increased significantly from the baseline level throughout the study period
      (P<0.05), serum propeptide of type-1 procollagen (P1CP) level also increased
      significantly from the baseline level throughout this period (P<0.001).
      Furthermore, significant increase from the baseline value (P<0.01) was observed
      in serum osteocalcin level at 6, 12 and 18 months. CONCLUSIONS: These results
      indicate that switching to 1alpha-hydroxycholecalciferol therapy after short-term
      HRT increased both bone resorption and bone formation, and permitted maintenance
      of increase in bone mass due to HRT for at least 18 months, though this switching
      accelerated bone turnover. This may have occurred because stimulation of bone
      formation induced by HRT was maintained by 1alpha-hydroxycholecalciferol, though
      bone turnover was slightly promoted because of withdrawal of HRT. This method was
      thus found to be very effective in preventing bone loss in patients who have
      discontinued HRT and are considered relatively contraindicated for use of
      estrogen.

PMID- 12787971
TI  - The prevalence of symptoms possibly related to the climacteric in pre- and
      postmenopausal women in Linkoping, Sweden.
AB  - BACKGROUND: Some extragenital symptoms have been suggested to be associated with
      the menopause and thus to be affected by estrogen status. In such case
      extragenital symptoms may be more frequent in postmenopausal women without
      hormone replacement therapy (HRT) than in premenopausal women or women using HRT.
      OBJECTIVE: To assess if the prevalence of a number of extragenital symptoms is
      higher in postmenopausal women without than with HRT, or in premenopausal women
      of the same age. MATERIAL AND METHODS: All women aged 53 and 54 years in the
      community of Linkoping (n=1760) were sent a validated questionnaire about use of
      HRT, time since last menstruation and about different extragenital symptoms.
      RESULTS: 1298 (73.8%) women answered the questionnaire and answers from 1180
      (67%) women were possible to analyze. Postmenopausal women woke up significantly
      more often during night than premenopausal, and those without HRT often due to
      hot flushes and sweating. Women with HRT reported more muscular pain than the
      others. We found no other significant difference in prevalence of extragenital
      symptoms between the three groups of women. CONCLUSIONS: Sleeping disorders,
      arthralgia, xerophthalmia, xerostomia and dry skin are not more prevalent in 53
      and 54 years old postmenopausal women without HRT than in women with HRT or in
      premenopausal women of the same age. It may still be that some of these symptoms
      are related to estrogen deficiency, but do not develop until some years after
      menopause. It may also be that women with the most severe symptoms decided to use
      HRT and thereby decreased symptoms to the same level as in non-users.

PMID- 12787972
TI  - Sources of information and HRT prescribing practices among gynecologists in
      Puebla, Mexico.
AB  - OBJECTIVE: The purpose of this study was to determine the sources of information
      and hormone replacement therapy (HRT) prescribing practices of gynecologists in
      the capital city of Puebla, Mexico. METHODS: Practicing gynecologists (n=44) in
      29 colonias (neighborhoods) in the city of Puebla completed a self-administered
      standardized questionnaire. Survey topics included primary sources of information
      about HRT, discussion of patient health practices, awareness of alternative
      medicines, and HRT prescribing practices. RESULTS: Medical journals, hospital
      presentations, and textbook manuals were rated as the primary sources of
      information about HRT by 69-73% of physicians. Patients were rated as a primary
      source of information by 25% of physicians, and pharmaceutical representatives by
      16% of physicians. Almost all physicians reported a willingness to discuss diet,
      smoking habits and other health issues with their patients. Natural and herbal
      medications were recommended by 25% of physicians. Contrary to studies in the US,
      more male than female physicians reported recommending hormones to 90-100% of
      their menopausal patients (60 vs. 33%, n.s.). CONCLUSIONS: This study revealed
      that physicians utilize a wide range of information about HRT, including patients
      and pharmaceutical representatives. Physicians' willingness to list patients as a
      source of information about HRT indicates the degree to which patients are
      involved in the medicalization of menopause. Reasons given for prescribing HRT
      (e.g. prevention of osteoporosis) were similar to those identified in studies in
      the US and Canada. Some variation in physician attitudes and practices related to
      HRT was apparent within the city of Puebla, Mexico.

PMID- 12787973
TI  - Association between ovulation induction and early menopause--a cohort effect?

PMID- 12787974
TI  - [Indications, efficacy and tolerance of drug therapy in view of improving
      recovery of consciousness following a traumatic brain injury].
AB  - OBJECTIVE: To review the literature about the indications, efficacy, limits and
      tolerance problems of drugs used with the aim of improving recovery of
      consciousness after a traumatic coma. METHODS: Query using Medline, Embase,
      Neurosciences and Pascal databases. Thirty-two references were selected,
      including:articles proposing a synthesis of recent knowledge concerning
      neurotransmitters involved in vigilance, the pathophysiological mechanisms of
      impairment and the related pharmacology;clinical studies examining the efficacy
      of large categories of pharmacological agents (dopaminergic drugs,
      psychostimulants, tricyclic antidepressants and others) on vigilance and on
      alteration of consciousness following brain lesions. RESULTS: The synthesis
      provides evidence about the theoretical actions and efficacy of the available
      pharmacological agents. The clinical studies are less convincing: indications and
      therapeutic choices are empirical. Studies report often single cases. Randomised
      studies are rare, often heterogeneous concerning the aetiology of the brain
      lesions. The evaluation scales are varied and too wide. In this context,
      amantadin, amphetamine, methylphenidate and bromocryptin showed some positive
      effects. Despite a pessimist general feeling, some cases of unexpected recovery
      as well as relapses during breaks in treatment were arguments in favour of the
      drug that was administered. DISCUSSION/CONCLUSION: This review suggests that drug
      treatments for awakening might become a useful and perhaps even indispensable,
      complement in case management. It is therefore urgent to design multicentre
      studies in order to set rational indications and to develop realistic therapeutic
      protocols.

PMID- 12787975
TI  - [Influence of obesity on postural capacities of teenagers. Preliminary study].
AB  - OBJECTIVE: The purpose of this work was to define the influence of obesity on
      static postural control of teenagers. SUBJECTS AND METHOD: Nine obese subjects
      and seven non-obese subjects were characterised with stabilometric data of
      surface, of lengths and spontaneous sway in the lateral (X) and antero-posterior
      (Y) axis with open eyes and closed eyes in two conditions on firm floor and foam
      floor condition. RESULTS: For length data, significative differences were
      observed between the two groups for the opened eyes condition (p < 0.02) and eyes
      closed (p < 0.03) during foam floor condition. CONCLUSION: During experimental
      solicitations, obesity influences significatively the postural control of
      teenagers. Instead of systematic statistic differences, we observed a decrease in
      balance capacities of obese subjects. The effects of fat tissue distributions
      were not verified.

PMID- 12787976
TI  - [Biomechanical consequences of a knee osteoarthritis on the opposite lower limb].
AB  - The aim of this work was to study the compensatory strategies built up by
      patients with unilateral knee arthritis during stair descent. These compensatory
      strategies might induce increased biomechanical constraints on the unaffected
      knee. METHOD: A kinetic and kinematic analysis was performed in 11 patients with
      unilateral knee arthritis and in 14 control subjects using an ELITE system and
      two force-plates. The peak of vertical ground reaction forces when landing on the
      reception force-plate, the time to reach the peak and the duration of the
      different phases of the movement were studied during stair descent. RESULTS: The
      peak of vertical ground reaction forces was more important when landing on the
      unaffected limb than when landing on the affected limb. The time to reach this
      peak was longer in patients than in controls no matter which side was supporting.
      The duration of the single support phase was longer on the unaffected limb than
      on the affected limb. DISCUSSION AND CONCLUSION: This work has shown that
      patients with unilateral knee arthritis develop new strategies during stair
      descent. These new strategies imply increased biomechanical constraints on the
      unaffected limb and might favor arthritis on the sound side. These results
      support the idea that rehabilitation protocols of patients with unilateral knee
      arthritis should also involve the unaffected limb.

PMID- 12787977
TI  - [Comparative study of effort training in deconditioned patients with and without
      pain. A preliminary study].
AB  - INTRODUCTION: The deconditioning or disuse syndrome is a recent nosological
      entity, based on medical, professional, social and psychological arguments. The
      aim of the study was to measure the physical condition in deconditioning
      situation and to evaluate the effectivity of a training program on five chronic
      painful patients and five painless subjects. METHODS: After determining the
      physical aspects of the deconditioning syndrome using three tests and evaluating
      pain, this prospective study evaluated the benefits of a six weeks effort
      training period called "interval training" in subjects with and without chronic
      pain. The inclusion criteria were the patient's consent, the absence of
      etiological treatment of the pain and the absence cardiotropic medication. The
      data were compared using the t-test of Student. After the training protocol,
      people were satisfied. A significant increase of Maximum Oxygen Uptake, Maximum
      Tolerance Power duration of recovery and cardiac adaptation of effort were
      observed. Pain didn't seem to be a limited factor to cardiac effort training and
      decreased actively after the program. CONCLUSION: A training effort protocol can
      help to reduce the deconditioning syndrome whether people are painful or not. The
      improvements of physical parameters seem to be reinforced by a better self
      assurance.

PMID- 12787978
TI  - [Physical fitness reconditioning].

PMID- 12787979
TI  - [Rehabilitation after shoulder rotator cuff surgery: in-patient or day
      hospitalization (about 76 cases)].
AB  - OBJECTIVE: To define criteria of orientation in day-hospitalized or in-patient
      after shoulder rotator cuff surgery. METHOD: Population of 71 patients (53.2
      years +/-7) (76 shoulders) operated for rotator cuff tear by the same surgeon,
      then treated by physical therapy either in day-hospitalization or in-patient.
      Weekly, evaluation until the second month after surgery by setting as criteria:
      pain, passive and active range of motion and complications. RESULTS: Fifty-three
      shoulders benefited from rehabilitation therapy in hospitalization and 23 in day
      hospitalization. There is no significant difference for criteria studied between
      the 2 populations except for pains at the fifteenth day after surgery. Pain and
      articular steepness seem more frequent if the surgery is complex. DISCUSSION: Day
      hospitalization and in-patient give equivalent results, which explain themselves
      by the possibility of identical physical medicine and rehabilitation
      performances. The knowledge of the social context is important to choose the most
      adapted rehabilitation type because patients can benefit from assistance for the
      acts of the daily life and the domestic tasks. In-patient allows more comfort but
      implies a familial break.

PMID- 12787981
TI  - In vitro assessment of proximal polyethylene contact surface areas and stresses
      in mobile bearing knees.
AB  - Wear of the polyethylene (PE) insert in total knee arthroplasty remains a
      significant problem. The generation of biologically active wear particles may
      ultimately affect implant longevity through osteolysis or premature/catastrophic
      PE failure. The rate and pattern of wear is influenced by many factors, including
      component geometry and individual loading conditions, which determine the contact
      surface area and kinematics of the reconstructed knee. Contact areas and stresses
      at the proximal femoral-PE insert interface and distal PE-tibial interface
      contact surface areas were measured in nine mobile bearing total knee designs at
      0, 30, 60, 90 and 110 degrees of flexion at 3600 N (5 x body weight) using a
      standardized test method. Proximal and, to a lesser degree, distal interface
      contact area footprints decreased significantly with increasing flexion angle
      based on the conformity of the designs, resulting in a corresponding increase in
      the mean and peak stresses.

PMID- 12787983
TI  - The biomechanical environment of a bone fracture and its influence upon the
      morphology of healing.
AB  - The mechanism by which mechanical stimulus of reparative tissues directs the
      pattern of healing of a bone fracture is not understood. Several hypotheses have
      been developed that predict the ossification pattern during healing for a given
      ambient mechanical environment. These have remained unproved because of the
      absence of data on stress fields in the reparative tissue of real fractures. The
      present study examines the predictive performance of the most recent hypothesis
      that was proposed by Claes and Heigele (J. Biomech. 32 (1999) 255), against
      measured and calculated data from the clinical fracture reported by Gardner et
      al. (J. Biomech. 33 (2000) 415). The hypothesis was used to predict ossification
      from the preceding stress and strain fields present in the FEM of Gardner et al.
      at four temporal stages during healing. Predictions were then compared with the
      observed differentiation and maturation. During early healing of the
      interfragmentary gap region, the hypothesis correctly predicted the formation of
      connective tissue and fibrocartilage, and during later healing it correctly
      predicted the beginning of endochondral ossification. At the periphery of the
      periosteal callus, the hypothesis correctly predicted intramembraneous
      ossification during early healing, and also its thickening by endochondral
      ossification during later healing. However, the hypothesis incorrectly predicted
      intramembraneous ossification during early healing of the main periosteal callus,
      although in later healing it correctly predicted endochondral ossification.

PMID- 12787982
TI  - Relationships between material properties and CT scan data of cortical bone with
      and without metastatic lesions.
AB  - Breast, prostate, lung, and other cancers can metastasize to bone and lead to
      pathological fracture. To lay the groundwork for new clinical techniques for
      assessing the risk of pathological fracture, we identified relationships between
      density measured using quantitative computed tomography (rhoQCT), longitudinal
      mechanical properties, and ash density (rhoAsh) of cortical bone from femoral
      diaphyses with and without metastatic lesions from breast, prostate, and lung
      cancer (bone with metastases from six donors; bone without metastases from one
      donor with cancer and two donors without cancer). Moderately strong linear
      relationships between rhoQCT and elastic modulus, strength, and rhoAsh were found
      for bone with metastases (0.73<r<0.93, P<0.05). After accounting for differences
      in rhoQCT, the elastic modulus, compressive strength, tensile yield strain, and
      rhoAsh of bone with metastatic lesions differed from those of bone from donors
      without cancer (P<0.01). However, differences in tensile strength or compressive
      yield strain, after controlling for rhoQCT, were not found. Thus, these cancers
      degrade the elastic modulus and compressive strength, but not the tensile
      strength, of cortical bone beyond the amount that would be expected from
      decreased density alone. The rhoQCT-mechanical property relationships reported
      may be useful for evaluating bone integrity and assessing the risk of fracture of
      bone with metastases.

PMID- 12787984
TI  - Inflation of a pressure-limited cuff inside a model trachea.
AB  - A theory of the elastic behaviour of thin rubber films is developed to describe
      inflation of pressure-limited tracheal tube cuffs (a) outside and (b) inside
      rigid cylindrical model tracheas. At each stage, assumptions and results were
      successfully checked against experiment. The theory predicts cylinder wall versus
      intracuff pressure. This allows, for any suitable cuff (of which there are many),
      the determination of a single intracuff pressure that ensures a satisfactory
      seal, for any diameter within the human adult range, the wall pressure staying
      below some chosen safety limit.

PMID- 12787985
TI  - The influence of mean heart rate on measures of heart rate variability as markers
      of autonomic function: a model study.
AB  - Some studies have demonstrated that the assessments of autonomic activities from
      the alterations of heart rate variations (HRVs) after autonomic blockade and
      during exercise of high intensity by the spectral analysis of HRV seemed
      inconsistent with actual situation. The inconsistency is probably caused by the
      contributions of fluctuating magnitudes and mean levels of autonomic activities
      on HRV having not been clarified. The alterations of HRV after autonomic blockade
      and during exercise of high intensity using a mathematical model were simulated.
      The autonomic activity in normal condition was assumed first according to some
      experimental evidence. Then autonomic activities after sympathetic blockade,
      vagal blockade and during exercise of high intensity were appropriately adjusted
      accordingly. The HRVs in response to these given autonomic activities were
      simulated. We found that the effect on HRV influenced by the mean level of
      autonomic activity is helpful to explain alterations of HRV in these conditions.
      After vagal blockade, a largely reduced low frequency (LF) power could be caused
      by the reduced mean heartbeat interval induced by a decreased mean level of vagal
      activity. Increased low and high frequency powers after sympathetic blockade
      could be caused by the increased mean heartbeat interval induced by a decreased
      mean level of sympathetic activity. A decreased LF power during exercise of high
      intensity, in addition to the withdrawal of vagal activity, could also be caused
      by the decreased mean heartbeat interval induced by an increased mean level of
      sympathetic activity.

PMID- 12787986
TI  - Silicon dermabrasion tools for skin resurfacing applications.
AB  - Miniature abrasion tools for potential skin resurfacing applications are created
      using microelectromechanical systems (MEMS) fabrication technology. The abrading
      microstructures are formed on silicon wafers by a bulk micromachining process
      based on isotropic xenon difluoride etching. The micromachined abraders
      (microdermabraders) are packaged and applied to human cadaveric skin to assess
      abrasion quality. Plastic (acrylic) microreplicated structures, non-coated and
      aluminum-coated versions, are also used in a similar fashion. Non-textured
      silicon and plastic samples are used as study controls. Dermabraded and intact
      skin regions are analyzed qualitatively and quantitatively by light microscopy,
      image processing techniques, and histology. The microdermabraders exhibit a
      cleaner, more uniform abrading pattern on the cadaveric skin compared to the
      plastic microreplicated structures. Furthermore, the microdermabraders provide a
      consistently uniform cut through the epidermal layer, leaving little debris and
      minimal pitting. In contrast, the plastic microreplicated structures exhibit non
      uniform abrading patterns and leave behind more debris and eccentric pits. The
      results suggest micromachined dermabraders can successfully abrade fine
      dermatological flaws in human skin.

PMID- 12787987
TI  - Plantar soft tissue loading under the medial metatarsals in the standing diabetic
      foot.
AB  - Diabetes mellitus (type 2) is the most frequent cause of non-traumatic lower-limb
      amputations. The major cause of impairment to the feet of diabetics is persistent
      hyperglycemia, potentially leading to peripheral neuropathy as well as to
      pathological changes in plantar soft tissue, which stiffen its structure and
      diminish its ability to effectively distribute foot-ground contact loads. In this
      study, a computational model of the foot structure in the standing position was
      utilized to evaluate stress distributions in plantar soft tissue under the medial
      metatarsal heads of simulated diabetic versus normal feet. The model comprises
      five anatomic planar cross-sections in the directions of the foot rays, which
      were solved for internal stresses under static ankle joint reaction (300 N) and
      triceps surae muscle forces (150 N) using the finite element method. Tissues were
      assumed to be homogenous, isotropic and elastic materials, with nonlinear stress
      strain relations for the ligaments, fascia and plantar tissue. The model revealed
      significant tension stress concentrations (90-150 KPa) in the plantar pad of the
      simulated diabetic forefoot: they were four times the normal maximum stress under
      the first metatarsal head and almost eight times the normal maximum stress under
      the second metatarsal head. It was shown that with increased severity of
      stiffening of the plantar pad, as related to glucose-exposure, peak forefoot
      contact stresses may rise by 38 and 50% under the first and second metatarsal
      heads, respectively. The increase in averaged (von Mises) internal stresses
      within the plantar soft tissue is even more pronounced, and may rise by 82 and
      307% for the tissue under the first and second metatarsal heads, respectively.
      These results, which conform to experimental data gathered over the last two
      decades, suggest that the process of injury in diabetic feet is very likely to
      initiate not on the skin surface, but in deeper tissue layers, and the tissues
      underlying the distal bony prominences of the medial metatarsals are the most
      vulnerable ones.

PMID- 12787988
TI  - Estimation of the respiratory frequency using spatial information in the VCG.
AB  - A new method for extracting respiratory signals from the ECG/VCG is presented.
      The method is based on the alignment of an observed VCG loop to a reference loop
      with respect to the transformations of rotation and time synchronisation. The
      resulting series of estimated rotation angles reflects respiratory-induced
      changes in the electrical axis of the heart. The respiratory frequency is
      estimated by power spectral analysis of the derived respiration signal. The value
      of respiratory modulation of the heart rate is considered by analysing the cross
      power spectrum of the signals related to rotation angles and heart rate. For
      comparison, a respiratory signal derived from the QRS area of two different leads
      is implemented. The performance of the methods is validated on a database with
      simultaneously recorded VCG and respiratory signals acquired from 20 healthy
      subjects. The agreement between the respiratory frequencies obtained from the
      derived and the respiratory signals is presented. The angle-based respiratory
      signal is found to produce the best agreement with a gross median error of only
      4.2%.

PMID- 12787989
TI  - Frequency spectral characteristics of standing balance in children and young
      adults.
AB  - Past research has shown that spectral frequency characteristics of a balance
      control system may be useful for early detection of minor changes in the system.
      Since there is a lack of information regarding the frequency spectrum of
      children's balance control system, this study was undertaken to investigate and
      compare the spectral frequency characteristics of standing balance control
      between children and young adults under altered sensory environments. Seventeen
      children (9 females, 8 males, mean age 7.8+/-0.9 years) and the same number of
      female and male young adults (mean age 21.1+/-1.3 years) were tested for standing
      balance under six sensory conditions. These conditions were created by crossing
      the three levels of the visual factor (open eye, closed eye, sway-referenced
      vision) with the two levels of the somatosensory factor (fixed foot support,
      compliant foot support). The median spectral frequencies of the shear forces in
      the anterior-posterior (A/P) and the medial-lateral (M/L) directions were used as
      dependent variables. The results showed that children had higher median spectral
      frequency of the A/P shear force than young adults and this difference was not
      affected by the somatosensory factor. The median spectral frequency in the M/L
      direction was not different between the groups. The higher rate of body mass
      vibration of children in the A/P direction implies that children may not have
      fully developed the ankle strategy for maintaining standing balance, but
      nonetheless have developed the same efficiency of using vision for their
      reference of standing balance.

PMID- 12787990
TI  - An improved approach for measurement of stroke volume during treadmill exercise.
AB  - In this study, a new ensemble averaging technique was developed to measure
      cardiac output during treadmill exercise. Each dz/dt peak is used as a starting
      point for ensemble averaging, instead of the conventionally used R point of ECG,
      in order to prevent the peak dz/dt waveform (C point) to be smoothed, which
      results in increased dz/dtmax. When using the R point as a reference, time
      interval from the R point to the peak dz/dt varies for each heart beat. Signal to
      noise ratios (SNR) of the five subjects with the new technique were 12.9, 16. 4,
      10.6, 14.0, and 4.6% higher than those with the conventional one at rest and
      during four levels of exercise, respectively. Power density spectra of the
      averaged dz/dt waveforms by the peak dz/dt and R point referencing were also
      analyzed. Stroke volumes of the five subjects averaged by the peak dz/dt were
      4.9, 6.8, 7.6, 7.4, and 9.8% higher than those by the R point at rest and during
      four levels of exercise, respectively.

PMID- 12787992
TI  - Biomechanics of anterior knee pain.

PMID- 12787991
TI  - The use of a reconstructed three-dimensional solid model from CT to aid the
      surgical management of a total knee arthroplasty: a case study.
AB  - The use of a rapid prototyping method was utilised to produce a pre-operative
      solid model of the proximal tibia in a patient with a massive defect of the
      medial tibial plateau. The solid model was reconstructed from aligned sequential
      CT images of the knee. This was then used to determine the level of bone
      resection of the proximal tibia for the optimum placement of the tibial component
      of a total knee replacement. This technique gives the surgeon both the three
      dimensional anatomical information needed to ascertain whether there is adequate
      bony support after cutting for the prosthesis, as well as a solid model on which
      to carry out the proposed surgery, before undertaking the procedure on the
      patient.

PMID- 12787994
TI  - Analysis of the Leeds-Keio ligament for extensor mechanism repair: favourable
      mechanical and functional outcome.
AB  - Many techniques have been described for the challenging problem of extensor
      mechanism rupture, including the use of synthetic grafts. In 1994 Fujikawa et al.
      [J. Bone Surg. 1994:76B:200-203] reported excellent results using the Leeds-Keio
      polyester ligament. Patients were mobilised early, had few post operative
      complications and minimal extensor lag. This is the first independent assessment
      of this technique using both subjective and objective analysis of outcome. We
      reviewed 11 patients (12 knees) whose extensor mechanisms were repaired as
      described in the original paper. At a mean of 3 years after surgery there were no
      infections and no re-ruptures. Good functional recovery was observed with a mean
      Tegner activity score of 1.7, Lysholm score of 66 and Irrgang score of 58%.
      Indeed, 80% of working patients returned to their former employment. However,
      objective tests showed peak extensor torque recovered to only half normal
      strength. We conclude the results of this technique of repair compare favourably
      with other described techniques especially in complex cases.

PMID- 12787993
TI  - Use of the Leeds-Keio prosthetic ligament for repair of patellar tendon rupture
      after total knee arthroplasty.
AB  - We describe a technique for repair of the patellar tendon rupture after total
      knee arthroplasty (TKA), using the Leeds-Keio (L-K) prosthetic ligament. Two
      patients were followed for a mean of 38 months. Knee extension power and improved
      function were obtained in both cases. Use of the L-K ligament is a treatment
      option for repair of patellar tendon rupture following TKA.

PMID- 12787995
TI  - Theoretical use of 3D CT to predict method of patella realignment.
AB  - Procedures for the treatment of patello-femoral malalignment are grouped into two
      categories, proximal realignment and distal realignment. However, no clear
      indications in respect of these realignments have been reported. We have tried to
      evaluate patello-femoral alignment three-dimensionally using CT. The results lead
      us to group patients with recurrent patella dislocation into three types. Type 1
      comprises patients with normal patello-femoral alignment. Type 2 comprises
      patients whose patella only deviates laterally and who need proximal realignment.
      Type 3 comprises patients whose patella and tibial tuberosity both deviate
      laterally and who need both proximal and distal realignment.

PMID- 12787996
TI  - Cold legs: a potential indicator of negative outcome in the rehabilitation of
      patients with patellofemoral pain syndrome.
AB  - PURPOSE: The purpose of this paper is to explore the link between a poor outcome
      in response to an exercise based approach to physiotherapy, in patients with
      patellofemoral dysfunction and a self-report of legs feeling cold even in warm
      surroundings. SCOPE: The study was carried out in the physiotherapy outpatients
      department of Burnley General Hospital, Lancashire, UK with 87 consecutively
      referred patients with a diagnosis of patellofemoral pain syndrome being assessed
      for suitability for entry into the study. Of these 77 entered the study with 14
      (18%), of these responding 'Yes' to the question 'Do your legs feel cold even in
      warm surroundings?' All patients were assessed using four outcome measures prior
      to the commencement of a standardised rehabilitation programme consisting of
      lower limb biarticular muscle stretching, vastus medialis training and patella
      taping or biofeedback. The patients were reassessed using the same outcome
      measures 3 months after completing their course of treatment. CONCLUSIONS:
      Patients who responded 'Yes' to the question 'Do your legs feel cold even in warm
      surroundings?' reported higher pain levels and tolerated less physical activity
      than non-cold sufferers at initial assessment, these differences were
      statistically significant. The cold sufferers showed less improvement on all of
      the outcome measures although the differences between the two groups only reached
      statistical significance for one of the outcome measures. The implications of
      this in relation to clinical practice are discussed.

PMID- 12787997
TI  - Giant cell tumour of the patellar tendon sheath--an unusual cause of anterior
      knee pain: a case report.
AB  - We present a case of a giant cell tumour of the patellar tendon sheath with
      anterior knee pain. The relevant MRI findings and differential diagnosis of such
      lesions is discussed here.

PMID- 12787998
TI  - Clostridium infection in a knee extensor mechanism allograft: case report and
      review.
AB  - An unusual case of Clostridium perfringens infection after an allograft
      reconstruction of an extensor mechanism in a multiply revised total knee
      arthroplasty is reported. The case occurred in an elderly patient with an
      underlying bleeding dyscrasia who had previously undergone two revision total
      knee arthroplasties. The patient was treated by open irrigation, debridement,
      removal of allograft and prosthesis, intravenous antibiotics, and implantation of
      an antibiotic impregnated cement spacer utilizing an intramedullary rod.

PMID- 12787999
TI  - Can knees kneel? Kneeling ability after total, unicompartmental and
      patellofemoral knee arthroplasty.
AB  - This study investigates patients' perception of kneeling ability before and at 1
      and 2 years after total, unicompartmental knee replacement (UKR) and
      patellofemoral knee replacement (PFR), for osteoarthritis. Kneeling is an
      important function of the knee joint required for many daily activities and
      inability to kneel after knee surgery is a frequent cause of dissatisfaction.
      Data were prospectively collected on 253 knees. A kneeling score was obtained by
      analysis of the relevant section of the Oxford knee score. Scores were obtained
      pre-operatively and at 1 and 2 years post-operatively. Absolute values and change
      following surgery were recorded. Correlations with pain and other knee functions
      were also made. Kneeling ability prior to surgery was poor in all 3 groups (80%
      found it extremely difficult or impossible to kneel) and improved in all groups
      after surgery (20% had little or no difficulty to kneel at 2 years). Kneeling
      ability was best in UKR and worst in PFR. These results suggest that kneeling
      ability in osteoarthritic patients is poor but improves with knee arthroplasty
      surgery, however the majority of patients will still have difficulty in kneeling.

PMID- 12788000
TI  - When should we do knee replacements?
AB  - It is not known whether it is better to perform total knee replacements early or
      late in the course of arthritis. To examine the determinants of patient-related
      outcomes after knee replacement, we examined 812 patients in the Avon knee
      registry, in whom pre-operative and 5-year post-operative American Knee Society
      Scores were available. Ninety percent had a good outcome at 5 years. Women had
      significantly more severe disease at the time of surgery than men. Older people
      (>79 years) had the worst disease at the time of surgery, and made the least
      health gain, although their overall outcomes were still good. Those with the most
      severe disease at the time of operation made greater gains to those with less
      disease, but remained in worse health at 5 years, suggesting that earlier surgery
      may be preferable.

PMID- 12788001
TI  - Five year review of the Rotaglide total knee arthroplasty.
AB  - In this study we present the outcome for patients with the Rotaglide mobile
      meniscal knee prosthesis implanted for osteoarthritis. All patients reviewed had
      this prosthesis implanted as a primary total knee Arthroplasty in Crosshouse
      Hospital. The minimum follow-up period was 5 years (range 5-8.2). Patients were
      assessed clinically by the junior author (C.W.) and results were standardised
      using the Hospital for Specialist Surgery (HSS) knee score. Standard radiographs
      were taken in antero-posterior and lateral planes to assess for loosening using
      the Knee Society roentgenographic system. Case notes were then examined for
      evidence of peri and post-operative problems. Sixty-seven patients (71 knees)
      were reviewed. Ninety-four percent of patients had an excellent clinical outcome
      with HSS scores of 85 or more. Two knees were revised, one for meniscal fracture
      and one for meniscal dislocation. Both of these failures were early in our series
      and in a total of 312 knees to date there have been no other meniscal failures.
      No knees were revised for aseptic loosening and there have been no deep
      infections. We feel this prosthesis offers a safe and effective treatment for
      osteoarthritis with a good clinical outcome at 5 years with a low level of
      complications.

PMID- 12788002
TI  - The St. Leger total knee replacement--a 7-year clinical assessment and
      survivorship analysis.
AB  - The St. Leger total knee replacement was developed with the aim of producing an
      affordable prosthesis which contained the best known features of current designs
      and also allowed ease of instrumentation. We present the medium term clinical and
      radiographic outcome and survivorship of the prosthesis. From 1992 to August
      1994, 150 St. Leger total knee replacements were performed on 53 male and 72
      female patients. Mean age was 67 (Range: 40-86). Sixty-nine percent of operations
      were for osteoarthritis and 30% for rheumatoid arthritis. Patients were reviewed
      at 1, 4 and 7 years postoperatively by an independent assessor. One hundred and
      twenty-three patients were assessed at 4 years and 83 patients at 7 years. The
      American Knee Association Scores revealed 84% excellent or good, 9% fair, and 7%
      poor results at 7 years. No patients complained of severe pain, 90% had mild or
      no pain, 10% had moderate pain. Eighty nine percent of patients were satisfied
      with their outcome. There were five complications requiring revision: infection
      (2), loosening (1), valgus instability (1) and knee stiffness (1). Survivorship
      analysis revealed 95% (95% CI +/-7.2%) survival at 7 years. Total knee
      replacement using the St. Leger knee prosthesis has comparable results to other
      condylar knee systems that cost almost twice the price.

PMID- 12788003
TI  - The St. Leger total knee replacement. A false economy?
AB  - We reviewed the outcome of 53 primary St. Leger total knee replacement (TKR)
      implanted into 47 patients over a 2-year period from March 1995 and compared the
      outcome with age and sex matched controls with the Kinemax Plus TKR. All
      operations were performed to treat osteoarthritis of the knee. The St. Leger
      replacements were done in a Teaching Hospital by a Consultant surgeon while the
      Kinemax Plus replacements were done in the same hospital by two other surgical
      teams. During the period of review, 13 patients (13 knees) with St. Legers died
      or were too demented to participate, and 4 were lost to follow up. Eleven
      patients (13 knees) with the Kinemax died or were too demented to cooperate, and
      2 patients (2 knees) were lost to follow up. The St. Leger group had inferior
      Oxford Knee Scores to the Kinemax group but this was not significant. The St.
      Leger group had significantly worse survivorship of the prosthesis. The St. Leger
      prosthesis was cheaper (Pound sterling 650) than the Kinemax (Pound sterling
      1150). The initial saving was dwarfed by the ultimate cost of revision
      procedures.

PMID- 12788004
TI  - Fixed flexion deformity and flexion after knee arthroplasty. What happens in the
      first 12 months after surgery and can a poor outcome be predicted?
AB  - Fixed flexion deformity and flexion of 284 knee replacements were recorded pre
      operatively at 6 weeks and 12 months after surgery. Eighteen knees (6.3%)
      achieved unsatisfactory movements at 12 months. Seven knees (2.4%) had a fixed
      flexion greater than 10 degrees, six (2.1%) had flexion less than 90 degrees and
      five (1.8%) had both. The only pre-operative variable of predictive value for a
      poor outcome was a high fixed flexion deformity (10 out of 52 knees P<0.001).
      Only one out of 15 knees with limited pre-operative flexion was restricted
      afterwards. Seven knees (2.4%) with good pre-operative movements developed either
      limited flexion or a fixed flexion greater than 10 degrees, none had both. There
      were no post-operative events which contributed to this. Eight knees (2.8%)
      achieved very poor movements. In each case there was a significant post-operative
      event which contributed to this. Overall, the flexion achieved at 12 months was
      directly related to the pre-operative flexion. Those knees with <90 degrees of
      flexion gained 29.3 degrees (S.D. 18). Those with 130 degrees or greater flexion
      lost 15.2 degrees (S.D. 13.6). The mean pre-operative fixed flexion was reduced
      by 50% at 6 weeks and again at 12 months. Knees with a high fixed flexion
      deformity alone pre-operatively have an increased risk of developing stiffness
      afterwards even if the deformity is corrected at surgery. In most cases
      significant post-operative events play a major role in this outcome. A small
      percentage of knees develop stiffness without any obvious explanation.

PMID- 12788005
TI  - The consequences of lateral release in total knee replacement: a review of over
      1000 knees with follow up between 5 and 11 years.
AB  - BACKGROUND: The relationship between lateral release in total knee arthroplasty
      and subsequent patello-femoral problems is contentious. Variable rates of
      instability, patella fracture and other complications have been demonstrated
      after lateral release. Significant measures have been taken by some surgeons to
      avoid a lateral release. We wished to determine whether lateral release was
      detrimental or beneficial in terms of mid- to long- term patellofemoral problems.
      METHODS: We examined 1071 total knee arthroplasties with a follow-up of 5 to 11
      years to determine the longer-term consequences of lateral release. Lateral
      release was performed as clinically indicated after a 'no thumbs' assessment in
      51% of cases. The knees requiring a lateral release had lower pre-operative
      Hospital for Special Surgery (HSS) scores and demonstrated a greater improvement
      in post-operative HSS scores. RESULTS: The difference in HSS scores, between the
      groups, was significantly less post-operatively than prior to surgery. Overall,
      we had a high incidence of lateral release (51%), but low fracture rate (1.2%),
      and very low instability rate (0.6%). Only three surgeries were required for
      patello-femoral problems. CONCLUSION: This study suggests that any negative
      consequences of lateral release are minimal and we recommend lateral release
      continue to be performed as clinically indicated.

PMID- 12788006
TI  - Comparison of the lateral release rates in the press fit condylar prosthesis and
      the PFC Sigma prosthesis.
AB  - There are many different total knee replacements on the market. Most have
      undergone design changes since they were introduced. The manufacturers claim
      these changes are necessary to improve outcomes of their products. Johnson and
      Johnson changed their press fit condylar (PFC) knee to PFC Sigma. One of the
      reasons for the change was to improve patella tracking by combining the deeply
      radiused trochlear groove of the PFC cruciate sacrificing knee with the natural
      asymmetrical valgus angle of the PFC cruciate retaining knee. In 1995 we started
      a prospective audit of our knee replacements. We analysed our early outcomes to
      test this theory. Group 1 consisted of 468 patients who underwent 543 PFC
      replacements. Group 2 consisted of 359 patients who underwent 423 Sigma knee
      replacements. An audit nurse saw all the patients preoperatively and an American
      Knee Society Score was done. Operative details were recorded. Patients were
      followed up by an audit nurse at a dedicated knee clinic. The same surgeons using
      the same instrumentation carried out the operations. The change in design reduced
      the lateral release rate by 50% from 32 to 16%. The complications were similar in
      both groups and there was no difference in the outcomes at 6 months. The change
      in design from the PFC to the Sigma knee has had an effect in reducing the
      lateral release rate, without affecting the early outcomes. We plan to continue
      this audit to see if the change leads to less patellar problems in the future.

PMID- 12788007
TI  - Five year results of selective patellar resurfacing in cruciate sparing total
      knee replacements.
AB  - We performed a prospective study on 129 knees with a selective approach to
      patellar resurfacing. One hundred and five knees were followed up at an average
      of 57 months. Of these, 48 knees met the eligibility criteria, thus leaving 57
      knees with unresurfaced patellas. Mean follow up was 57 months. Parameters
      studied included HSS scores, pain, function, range of motion and patellofemoral
      symptoms including the ability to rise from a chair and to negotiate stairs.
      Approximately 90% good to excellent results were observed in both groups. The
      incidence of anterior knee pain and patellofemoral related problems was lower
      than the average reported in literature. None of the knees was revised for
      patellofemoral problems. Our findings suggest that the results of patellofemoral
      resurfacing with modern TKR designs are dependent on a careful patient selection
      and meticulous surgical technique. With a selective approach to resurfacing, one
      can achieve a high percentage of good results in both groups. Post-operative
      anterior knee pain is probably not related to the fact as to whether the patella
      is resurfaced or not.

PMID- 12788008
TI  - Patello-femoral cross-union an unusual cause for knee stiffness following primary
      knee arthroplasty.

PMID- 12788009
TI  - Total knee arthroplasty for neglected permanent post-traumatic patellar
      dislocation--case report.
AB  - Permanent post-traumatic patellar dislocation is a rare entity resulting from
      recurrent trauma. This uncommon condition is often confused clinically with
      congenital dislocation of the patella. Treatment options, although not well
      defined, include observation, various soft tissue and bony procedures for
      realigning the patella and patellectomy. To our knowledge, this is the first case
      reporting the use of conventional non-constrained total knee arthroplasty with
      patellar resurfacing and soft tissue realignment procedure for long-standing
      patellar dislocation in a single stage. An interesting feature of this case was
      the patient's ability to function reasonably well for nearly 40 years with a
      dislocated patella until the development of secondary osteoarthritis, and the
      surprisingly good recovery after total knee replacement.

PMID- 12788010
TI  - Tuberculosis vaccination: the long road to a better BCG.

PMID- 12788012
TI  - Fluctuating asymmetry and animal welfare: how far are we? And how far should we
      go?

PMID- 12788011
TI  - Chondrocyte apoptosis, inflammatory mediators and equine osteoarthritis.

PMID- 12788013
TI  - Diagnostic imaging of congenital porto-systemic shunts in dogs and cats: a
      review.
AB  - An overview of clinical, laboratory, and diagnostic imaging features of
      congenital porto-systemic shunt (PSS) in dogs and cats is presented through the
      analysis of recent literature, and personal case log. Particular emphasis is
      given to diagnostic accuracy of ultrasonographic examination of PSS in the
      evaluation of shunt vessel anatomy, and of ancillary findings such as
      abnormalities of portal vein flow, portal branches, and liver size. Operative
      mesenteric portography to obtain information on PSS morphology and position, and
      quantitative hepatic scintigraphy, which allows the calculation of shunt
      fractions, are also described. Limitations for each diagnostic imaging technique
      are given.

PMID- 12788014
TI  - Growth and developmental instability.
AB  - Developmental stability reflects the ability of an individual to develop a
      regular phenotype under given environmental and genetic conditions. Measures of
      developmental instability include the degree of fluctuating asymmetry and the
      frequency of phenodeviants. Endocrine, neural and circulatory mechanisms that
      control similar development of morphological characters on the two sides of the
      body are also involved in controlling overall development. Cross-validation
      studies have shown that measures of developmental instability are positively
      correlated with other measures of welfare such as tonic immobility in poultry.
      Asymmetric animals grow less rapidly than symmetric individuals. Eleven studies
      have investigated the relationship between growth rate and developmental
      instability, and the observed effect size (Pearson correlation coefficient
      adjusted for sample size) is -0.15. Studies of chickens have shown that asymmetry
      increases as a response to selection for increased growth rate. As conditions for
      rearing deteriorate by higher density, fluctuating asymmetry increases and growth
      rate decreases, both within and among farms. Fluctuating asymmetry can be
      considered a measure of animal welfare since larger values reflect worse
      environmental conditions as experienced by the individual animal itself. Since
      growth rate and fluctuating asymmetry are negatively correlated, we can infer
      that improvement of rearing conditions leading to reduced asymmetry will both
      benefit the producer (in terms of increased growth), but also the animals in
      terms of better conditions for rearing.

PMID- 12788015
TI  - Transcranial magnetic stimulation: review of the technique, basic principles and
      applications.
AB  - Transcranial magnetic stimulation is rapidly developing as a powerful, non
      invasive tool for studying the descending motor tracts in humans. The
      applications of the test in animals are for the moment restricted to small
      animals. However, this non-invasive, sensitive and painless technique appears
      promising as a test of motor tract function in horses where the neurological
      examination is mainly restricted to clinical evaluation and some ancillary tests,
      such as radiography, cerebrospinal fluid analysis and electromyography. In this
      review, we want to discuss the history, basic principles, technique and
      applications of transcranial magnetic stimulation in humans and small animals and
      indicate the possibilities for its use in horses. Since the great portion of this
      review is based on human studies, it is worthwhile to mention that the reports
      being described are from humans unless otherwise specified.

PMID- 12788016
TI  - Vaccinating badgers (Meles meles) against Mycobacterium bovis: the ecological
      considerations.
AB  - Bovine tuberculosis (TB) is a serious zoonotic disease, which despite a largely
      successful test and slaughter programme has persisted in cattle herds in parts of
      the UK. The badger (Meles meles) is widely considered to represent a significant
      wildlife reservoir for the transmission of Mycobacterium bovis to cattle, and has
      been the subject of a variety of culling strategies since the mid 1970s.
      Nevertheless, the incidence of herd breakdowns has continued to rise, and the
      efficacy of culling is currently the subject of a large-scale field trial. One
      potential alternative tool for the management of disease in wildlife populations
      is vaccination. However, the successful development of an effective vaccine and a
      strategy for its delivery will require careful consideration of the practical
      constraints imposed by ecological factors. In the current paper, we discuss
      relevant ecological and epidemiological characteristics of badger populations and
      practical aspects of vaccine delivery in the field.

PMID- 12788017
TI  - Articular chondrocyte apoptosis in equine osteoarthritis.
AB  - Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte
      apoptosis has been implicated as a major pathological OA change in humans and
      experimental animals but no studies have been performed on equine OA. Articular
      cartilage was collected from three normal and five OA horses. Histopathological
      changes were scored by a modified Mankin grading system. A terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was
      performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from
      chondrocytes was indirectly evaluated by immunohistochemistry with polyclonal
      antibody to nitrotyrosine. The histopathological score and percentage of
      chondrocyte apoptosis from the OA cartilages were significantly higher than from
      normal cartilages. There was a significant correlation between histopathological
      grade and the percentage of chondrocyte apoptosis. OA cartilages exhibited
      stronger immunoreactivity to nitrotyrosine than normal cartilage. Topographical
      distributions of chondrocyte apoptosis, cartilage matrix degeneration, and NO
      production overlapped in equine OA cartilages, suggesting that these pathological
      phenomena are closely interrelated.

PMID- 12788018
TI  - Quantitative electroencephalographic findings in beagles anaesthetized with
      propofol.
AB  - The purpose of this study was to assess quantitative electroencephalography (q
      EEG) in 10 healthy beagle dogs under propofol anaesthesia in order to determine
      objective guidelines for diagnostic electroencephalographic (EEG) recordings and
      interpretation. The basic pattern after preliminary visual examination of EEG
      recordings was characterized by spindles, k-complexes, vertex sharp transients,
      and positive occipital transients that were superimposed on the slow background
      activity. The results of the q-EEG were characterized by the prevalence of slow
      rhythms delta and theta, both in absolute and relative power spectrum analysis,
      while fast rhythms (alpha and beta) were poorly represented. The distribution of
      single frequency bands was widespread for delta, focal for frontal and central
      for theta, as well as for most alpha and beta patterns. The present study has
      shown that the use of quantitative EEG gives information on the frequency content
      of the bio-electrical activity and defines the distribution of the single
      frequency bands under a standardized anaesthetic protocol.

PMID- 12788020
TI  - Sensitivity of different prothrombin time assays to factor VII deficiency in
      canine plasma.
AB  - The factor VII sensitivity of prothrombin time (PT) in dogs was tested using five
      different PT reagents and a commercial PT variant. The five PT reagents were used
      according to manufacturers' instructions (standard test, PT([ST])) and also using
      a modified test instruction (modified test, PT([MT])). Plasma samples with
      defined factor VII levels (10-100%) were prepared by adding increasing quantities
      of canine factor VII deficient plasma to the pooled plasma of healthy dogs.
      Statistical comparison based on prothrombin time ratios (PTR = PT sample: PT
      measured for 100% factor VII activity level) revealed significant differences
      between different reagents for PT([ST]) and also for PT([MT]). Factor VII
      activity at which PT was prolonged to the upper limit of the reference values
      (FVII([X(0.975)])) was 16-39% (PT([ST])) and 23-35% (PT([MT])). Factor VII
      sensitivity measured by PTR and also by FVII([X(0.975)]) values, was higher in
      four of five PT reagents using PT([MT]) when compared with PT([ST]). The results
      of this study indicate the importance of selecting a sensitive reagent and method
      for PT measurement and for careful interpretation of PT test results using canine
      plasma.

PMID- 12788019
TI  - Evaluation of virucidal activity of three commercial disinfectants and formic
      acid using bovine enterovirus type 1 (ECBO virus), mammalian orthoreovirus type 1
      and bovine adenovirus type 1.
AB  - A modified version of the test method of the Comite Europeen de Normalisation
      (CEN) was developed using formic acid and three commercial disinfectants to
      evaluate virucidal activity against three non-enveloped viruses, bovine
      enterovirus type 1 (ECBO virus), mammalian orthoreovirus type 1 and bovine
      adenovirus type 1 (BAV 1). Determination of the effects of temperature was
      carried out at 20 and 10 degrees C. All tests with protein load used bovine serum
      albumin (BSA) and yeast extract. The investigations were performed in suspension
      tests and in carrier tests using poplar wood virus carriers. The carrier tests
      showed that ECBO virus could be inactivated at 20 degrees C with 1% formic acid
      within a 60 min reaction time. For disinfection of ECBO virus at 10 degrees C
      within 60 min, a 2% concentration of formic acid was necessary. Formic acid was
      ineffective against reovirus and bovine adenovirus and cannot be recommended as a
      reference disinfectant. Inactivation of ECBO virus and adenovirus type 1 using a
      disinfectant containing aldehydes and alcohols could be achieved, but only at
      room temperature. The disinfection of reovirus type 1 at room temperature with
      this product was possible without a protein load. This disinfectant exhibited
      disinfection ability at 10 degrees C at a concentration of more than 2% or with a
      longer exposure time. A disinfectant containing aldehydes was effective at room
      temperature but its effect was reduced in the presence of organic matter.
      Inactivation at 10 degrees C was found only against adenovirus. The fourth
      disinfectant, which contained peroxiacetic acid, inactivated all test viruses at
      a concentration of 0.5% within 15 min independent of temperature and protein
      load.

PMID- 12788021
TI  - Comparison of polymerase chain reaction and cell culture for the detection of
      Chlamydophila species in the semen of bulls, buffalo-bulls, and rams.
AB  - Two hundred and thirty six semen samples were collected from 120 bulls, 60
      buffalo-bulls, and 56 rams located on farms of known history of infection with
      Chlamydophila species. All semen samples were examined by polymerase chain
      reaction (PCR) and cell culture techniques for detection of Chlamydophila
      species. The primers were selected to allow the amplification of all target
      species in a single reaction by identifying conserved sequences in the omp2 gene.
      PCR assay detected more positive samples (36) from the semen samples collected
      from different animal species than were detected by the culture method (21). The
      results indicated that all culture-positive semen samples (21) from different
      species were PCR positive. The detection limit of the PCR assay was determined
      with DNA extracted from fourfold serial dilution of C. abortus (B577) and C.
      pecorum (11/88) cultures and found to be 0.25 inclusion-forming units (IFU) per
      PCR, while the culture method could not detect less than 4 IFU. This is the first
      report using PCR for the detection of Chlamydophila species in buffalo-bulls'
      semen and the assay provides a simple, sensitive, rapid, and reliable means for
      the detection and identification of the organism.

PMID- 12788022
TI  - Comparison between tail and jugular venipuncture techniques for blood sample
      collection in common chameleons (Chamaeleo chamaeleon).
AB  - The most common technique used for collecting blood samples from chameleons,
      ventral tail caudal venipuncture (Reptile care. An Atlas of Diseases and
      Treatments, Vol. II, T.F.H. Publication, New Jersey, 1991) sometimes presents
      undesired effects. Here we compared tail versus jugular vein venipuncture
      techniques in the common chameleon. In the first experiment, we collected 0.25%
      of the chameleon's body mass in blood from either tail or jugular sites in size
      matched pairs of animals to check for secondary effects. In a second experiment,
      we measured white blood cells (WBC), red blood cells (RBC), total plasma protein
      and uric acid in blood samples collected from both sites in the same individual.
      We found few secondary effects following the use of either venipuncture site
      although skin darkening was observed in few specimens when using the ventral tail
      vein. Blood profiles were similar between samples. The repeatability of
      measurements was similar in RBC and WBC counts and remarkably low (<0.90).
      Despite the few differences recorded, we recommend jugular venipunction in
      chameleons as skin darkening is unlikely, blood volumes are easily obtained and
      collection time is shorter.

PMID- 12788023
TI  - Neonatal piglet losses associated with Escherichia coli and Clostridium difficile
      infection in a Slovakian outdoor production unit.

PMID- 12788024
TI  - Pharmacokinetics of enrofloxacin and the rate of formation of its metabolite
      ciprofloxacin following intravenous and intramuscular single dose administration
      to male buffalo calves.

PMID- 12788025
TI  - C to A single nucleotide polymorphism in intron 18 of the human MST1R (RON) gene
      that maps at 3p21.3.
AB  - The MST1R (RON) gene, that maps at 3p21.3, encodes a protein tyrosine kinase
      receptor comprised of an extra-cellular domain that contains the ligand binding
      pocket and an intracellular region where the kinase domain is located. It
      controls cell survival and motility programs related to invasive growth. With the
      single strand conformation polymorphism (SSCP) method, a C to A nucleotide
      polymorphism (SNP) was found in intron 18 of the gene. The SNP has a frequency of
      0.28 among African-American, 0.25 among Caucasian CEPH and 0.09 among Asian
      healthy individuals. During these studies, an alternatively spliced cDNA of
      MST1R, lacking exon 19, was also found that may result from this change.

PMID- 12788026
TI  - Multiplex PCR using real time DNA amplification for the rapid detection and
      quantitation of HTLV I or II.
AB  - A multiplex 'real-time' polymerase chain reaction (PCR) has been established as a
      general technique for the quantitation of proviral human T-lymphotrophic virus
      types 1 and 2 (HTLV-I/II). The technology utilizes fluorescence to measure
      amplification products from the tax gene of Human T-cell lymphotropic virus type
      1 or the 5' long terminal repeat of Human T-cell lymphotropic virus type 2. The
      quantitative amplification of the standard was linear across four orders of
      magnitude with nearly identical amplification efficiencies for monoplex or the
      biplex format from 1.4 copes/assay (60 copies proviral DNA/0.5 micrograms human
      DNA) to 6000 copies/assay (240000 proviral copies/0.5 micrograms human DNA). The
      human beta-globin gene was used to normalize for human DNA input to determine the
      proviral DNA load. Three hundred fifty-six specimens received by Specialty
      Laboratories for HTLV I/II detection provided identical results in the detection
      of HTLV I/II proviral DNA. No additional positive specimens were identified with
      the biplex assay format. The coefficient of variation for the proviral DNA load
      was less than 30% for HTLV I or II quantitation (n=5). For spiked specimens, two
      groups of five separate 0.25 ml blood specimens (20 total) were spiked,
      respectively, with 0, 9.6, 48, 240 and 1200 copies of HTLV I or HTLV II DNA
      standards. The specimens were amplified with the HTLV I/II multiplex format.
      Twenty of twenty expected negative HTLV I or HTLV II specimens were negative
      (100% specificity) and 14/16 specimens spiked with 48 copies or more HTLV I were
      detected (87.5% sensitivity). Thirteen of sixteen HTLV II spiked specimens (>48
      copies of HTLV II standard per 10 assays) were detected (81.2%). The real-time
      detection provides accurate and reliable results in a single amplification for
      both HTLV (I or II) targets with a more rapid turnaround time and a decrease in
      material required for results.

PMID- 12788027
TI  - An assessment of a multiplex PCR assay for differentiating clinically important
      mycobacteria based on pncA gene variation.
AB  - The pncA genes in mycobacteria are responsible for the production of
      pyrazinamidase (PZase). In Mycobacterium tuberculosis, PZase hydrolyses
      pyrazinamide (PZA) to pyrazonic acid, a compound that possesses bactericidal
      activity against tubercle bacilli. Nucleotide sequences of pncA genes found
      within mycobacteria where aligned in an effort to ascertain the significance of
      any variability in sequence. Three sets of primers (one degenerate and five
      consensus sequences) were designed and employed in a multiplex PCR assay to
      amplify the pncA region in seven clinically common mycobacteria. The banding
      patterns generated from each species in conjunction with PZase activity tests
      demonstrated that the mycobacterial species examined could be clearly identified
      and differentiated from one another. Although not yet tested with clinical
      isolates, the combination of these two assays has provided a promising
      discriminatory tool for the identification of commonly encountered clinical
      mycobacteria species.

PMID- 12788028
TI  - Design of oligonucleotide arrays to detect point mutations: molecular typing of
      antibiotic resistant strains of Neisseria gonorrhoeae and hantavirus infected
      deer mice.
AB  - Microarrays are promising tools for use in molecular diagnostics due to their
      ability to perform a multitude of tests simultaneously. In the case of genotyping
      many such tests will require discrimination of sequence at the single nucleotide
      level. A number of challenges exist including binding of optimal quantities of
      probe to the chip surface, the use of uniform hybridization conditions across the
      chip and the generation of labeled target. We investigated two model systems to
      test out the efficacy and ease with which probes can be designed for this
      purpose. In the first of these we designed primers to identify five mutations
      found in two genes from N. gonohorroeae, gyrA and parC that have been implicated
      in ciprofloxacin resistance. In the second system we used a similar strategy to
      identify four mutations in AT rich mitochondrial DNA from deer mice. These
      mutations are associated with deer mice subspecies that originate from different
      geographical regions of Canada and harbor different hantavirus strains. In every
      case we were able to design probes that could discriminate mutations in the
      target sequences under uniform hybridization conditions, even when targets were
      fairly long in length, up to 400 bp. Our results suggest that microarray analysis
      of point mutations might be very useful for automated identification and
      characterization of pathogens and their hosts.

PMID- 12788030
TI  - Detection and discrimination of B pertussis and B holmesii by real-time PCR
      targeting IS481 using a beacon probe and probe-target melting analysis.
AB  - A beacon probe was designed to detect one of the two documented single nucleotide
      changes in IS481 target allele of Bordetella holmesii genome as compared to
      Bordetella pertussis. PCR amplified product targeting a region of IS481 in
      presence of the probe was subjected to a post-PCR hybridization and melting
      cycle. Hybrid of the probe with B. pertussis specific target had a different
      thermal stability than that with allele having the single nucleotide change in B.
      holmesii. The melting of B. pertussis-probe hybrid occurred in a single phase;
      while that of B. holmesii-probe hybrid was biphasic-one for allele identical to
      that in B. pertussis and the other for that with a single nucleotide change in B.
      holmesii genome, with a difference in melting temperature (T(m)) of 6.5 degrees
      C. The characteristic melting profile and T(m) analysis was the basis for
      discriminatory detection of B. pertussis from B. holmesii. The method was applied
      in a representative set of clinical isolates of B. pertussis and B. holmesii and
      the result was in agreement with conventional culture method.

PMID- 12788029
TI  - Detection of atovaquone and Malarone resistance conferring mutations in
      Plasmodium falciparum cytochrome b gene (cytb).
AB  - Clinical treatment failures of the hydroxynaphthoquinone atovaquone or its
      combination with proguanil (Malarone) in Plasmodium falciparum malaria has been
      recently documented. These events have been associated to single nucleotide
      polymorphisms (SNPs) in the parasite cytochrome b gene (cytb). In this report we
      describe a set of nest PCR-RFLP methods developed for the fast detection of all
      known cytb mutations associated to resistance to these drugs. The methods were
      successfully applied for the analysis of phenol-chloroform extracted DNA samples
      from patients not cured by Malarone, and from an established parasite clone.
      Further, the protocol for the detection of the A803C mutation was applied to 164
      DNA field samples extracted through crude methanol-based protocols, originated
      from several malaria settings. The PCR-RFLP methods here presented can be used as
      a valuable for the clinical detection and study of Malarone and atovaquone P.
      falciparum resistance.

PMID- 12788031
TI  - A comparison of sample preparation methods for PCR detection of pathogenic
      Yersinia enterocolitica from ground pork using swabbing and slurry homogenate
      techniques.
AB  - Two sample preparation methods for multiplex polymerase chain reaction (PCR) for
      detection of plasmid-bearing virulent Yersinia enterocolitica (YEP(+)) from
      ground pork were compared. Two sets of ground pork samples were inoculated with
      10, 1, and 0.5 CFU/cm(2) of a YEP(+) strain, one set was swabbed and the second
      set was dispersed into a slurry homogenate. Both swab and slurry homogenate
      samples were enriched in sterile Whirl Pak bags containing modified trypticase
      soy broth for 48 h at 12 degrees C. From the enriched swab samples, the bacterial
      cells were pelleted, washed, boiled in sterile distilled water, and treated with
      proteinase K to prepare cell lysates to use as a DNA template. Since slurry
      homogenate samples contained food material, DNA extraction was performed using a
      commercial kit. The DNA from cell lysates and from extracted slurry homogenate
      samples were evaluated as templates for multiplex PCR employing primers for the
      chromosomal ail and plasmid virF genes. The enrichment of the YEP(+) strain was
      more efficient using the sponge-swabbed samples than the slurry homogenate
      samples at all three inoculum levels tested. It was necessary to dilute the DNA
      extracted from slurry homogenate to determine the optimal concentration of each
      sample for PCR amplification. No amplification signal was detected using
      undiluted DNA, possibly due to DNA inhibitors present in the slurry homogenate
      that were not removed in the process of extraction. However, DNA could be
      detected in undiluted cell lysates from swab samples. Thus, the cell lysates from
      swab samples are more advantageous than DNA extracted from ground pork slurry
      homogenate samples for the PCR assay.

PMID- 12788032
TI  - Identification and quantification of Chlamydia pneumoniae in human
      atherosclerotic plaques by LightCycler real-time-PCR.
AB  - A real-time PCR assay for Chlamydia pneumoniae in human atherosclerotic plaques
      by the use of novel probes and FRET LightCycler technology, is described. The
      assay proved particularly suitable for the specific and quantitative detection of
      a low DNA copy number in conventional PCR-negative samples. Among fifteen nested
      PCR negative atherosclerotic plaques examined, our method detected three positive
      plaques containing 50(+/-3), 37(+/-2) and 24(+/-2) DNA copy number+/-SD in three
      independent experiments. Real-time PCR holds promise for C. pneumoniae
      quantitation in human atherosclerotic plaques.

PMID- 12788033
TI  - Molecular sub-grouping of enterovirus reference and wild type strains into
      distinct genetic clusters using a simple RFLP assay.
AB  - RFLP analysis and sequencing of RT-PCR amplicons in previous studies revealed the
      existence of intra-serotypic variability in the 5'-UTR of human enteroviruses,
      complicating the use of this method to serotype isolates. During the present
      study, the available sequences of many enterovirus reference and wild type
      strains were analysed in an attempt to discover restriction sites that would
      rapidly and reliably aid the classification of human enteroviruses into specific
      sub-groups on the basis of their 5'-UTR for diagnostic and/or epidemiological
      purposes. Despite intratypic genetic variability in the 5'-UTR, the results of
      the sequence analysis, as well as data from the RFLP analysis of 61 enterovirus
      reference strains from 60 different serotypes and 123 clinical isolates showed
      that one restriction endonuclease, HpaII, may contribute to a reliable sub
      classification of CAVs and the rest of enteroviruses, on the basis of 5'-UTR,
      into five genetic groups, which could be particularly useful in clinical and
      epidemiological studies. Although more sequence data from enterovirus reference
      and wild type strains may be required for the elaboration of a precise molecular
      identification system, the more possible genotypic classification into distinct
      clusters, as shown with the restriction enzyme HpaII, and the determination of
      the biological significance of this grouping (pathogenesis, epidemiology) might
      constitute an alternative means of enterovirus identification against
      conventional classification into distinct serotypes.

PMID- 12788034
TI  - A simple and rapid fluorescence-based immunoassay for the detection of
      staphylococcal enterotoxin B.
AB  - The bioterrorism threat is perceived to be a real challenge to our nation's
      security. This threat has necessitated the design of better and faster assays for
      the detection of biothreat agents including staphylococcal enterotoxin B (SEB), a
      causative agent of food poisoning. This study describes a simple, fast and highly
      sensitive fluorescence-based immunoassay, in which the antibody is fluorescently
      labeled for use in this assay. Use of labeled antibodies resulted in very low
      level of detection of SEB, 100 pg/well. This method is four times faster than
      classical and conventional enzyme-linked immunosorbent assay (ELISA).

PMID- 12788036
TI  - Brain plasticity in paediatric neurology.
AB  - Plasticity includes the brain's capacity to be shaped or moulded by experience,
      the capacity to learn and remember, and the ability to reorganize and recover
      after injury. Mechanisms for plasticity include activity-dependent refinement of
      neuronal connections and synaptic plasticity as a substrate for learning and
      memory. The molecular mechanisms for these processes utilize signalling cascades
      that relay messages from synaptic receptors to the nucleus and the cytoskeleton
      to control the structure of axons and dendrites. Several paediatric neurological
      disorders such as neurofibromatosis-1, Fragile X syndrome, Rett syndrome, and
      other syndromic and non-specific forms of mental retardation involve lesions in
      these signalling pathways. Acquired disorders such as hypoxic-ischaemic
      encephalopathy, lead poisoning and epilepsy also involve signalling pathways
      including excitatory glutamate receptors. Information about these 'plasticity
      pathways' is useful for understanding their pathophysiology and potential
      therapy.

PMID- 12788037
TI  - Ornithine transcarbamylase deficiency: a urea cycle defect.
AB  - The symptoms and signs of ornithine transcarbamylase deficiency are discussed.
      When the condition occurs among males in the neonatal period it is likely to be
      lethal. Pathological findings are non-specific. The diagnosis should be
      considered if coma with cerebral oedema and respiratory alkalosis occurs for no
      obvious reason. When hyperammonaemia is found, enzyme assay on a liver biopsy
      should be considered. A useful clue in an asymptomatic patient is a voluntary
      adoption of a vegetarian diet. Provocative tests, such as the allopurinol test
      can be used, but the method most frequently applied is mutation analysis. In the
      case of prenatal diagnosis this is possible on a chorionic villus sample. The
      prognosis of ornithine transcarbamylase deficiency is better for those with an
      onset after infancy, but morbidity from brain damage does not appear to be linked
      to the number of episodes of hyperammonaemia that have occurred. The syndrome
      results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase
      which catalyses the conversion of ornithine and carbamoyl phosphate to
      citrulline. The gene responsible for this enzyme is located on Xp21.1, and is
      expressed in the liver and gut. Mutations can be divided into two groups: those
      with neonatal onset with all enzyme activity abolished, and those with later
      onset with partial and varying enzyme deficiency. There can be a variety of
      precipitating causes, for example sodium valproate. Treatment can be given with a
      low protein diet, and with alternate pathway drugs such as sodium benzoate and
      phenylbutyrate. Liver transplant can be considered when symptoms are life
      threatening, although there may be severe complications.Gene replacement therapy
      is the hope of the future.

PMID- 12788038
TI  - Effect of levetiracetam in refractory childhood epilepsy syndromes.
AB  - In this open-label add-on study of levetiracetam in refractory childhood epilepsy
      syndromes, we studied the effect of a rapid introduction of levetiracetam on the
      total seizure frequency in 21 children, known to have partial and generalized
      seizures. Starting dosage was 10 mg/kg/day, increased every 4th day by 10 mg/kg
      up to a maximum of 60 mg/kg/day, depending on efficacy and tolerability. In this
      highly refractory population, 47% showed a seizure frequency reduction of more
      than 50%. Levetiracetam was effective both in partial and generalized seizures,
      with a significant effect on myoclonic seizures. Only mild side-effects were
      observed in four of 21 children, at a dosage of more than 40 mg/kg/day.

PMID- 12788040
TI  - Near-fatal cerebellar swelling caused by acute multifocal cerebellar necrosis.
AB  - We report a case of acute near-fatal cerebellar swelling, which was accompanied
      by multifocal cerebellar necrosis. Acute, near-fatal cerebellar swelling is a
      rare problem thought to be of parainfectious aetiology. Initiation by multifocal
      cerebellar necrosis has not been reported so far with this disorder.

PMID- 12788039
TI  - Profound skeletal muscle depletion of alpha-dystroglycan in Walker-Warburg
      syndrome.
AB  - Walker-Warburg syndrome (WWS) is an autosomal recessive disorder characterized by
      the combined involvement of the central nervous and skeletal muscle systems.
      Although the molecular basis of WWS remains unknown, defects in the muscle fibre
      basal lamina are characteristic of other forms of congenital muscular dystrophy
      (CMD). In agreement with this, some forms of CMD, due to glycosyltransferase
      defects, display a reduction in the immunolabelling of alpha-dystroglycan, whilst
      beta-dystroglycan labelling appears normal. Here we describe an almost complete
      absence of alpha-dystroglycan using both immunohistochemistry and immunoblotting
      in two patients with WWS. In addition, there was a mild reduction of laminin
      alpha 2. In contrast, immunohistochemical labelling of perlecan and collagen VI
      was normal. Linkage analysis excluded the recently identified POMT1 locus,
      responsible for a proportion of WWS cases. These results confirm that WWS is a
      genetically heterogeneous condition and suggest that disruption of the alpha
      dystroglycan/laminin-alpha 2 axis in the basal lamina may play a role in the
      degeneration of muscle fibres in WWS-also in cases not due to POMT1 defects.

PMID- 12788048
TI  - Relationship of demethylation processes to veratric acid concentration and cell
      density in cultures of Rhodococcus erythropolis.
AB  - The aim of this study was to investigate the correlation between veratrate
      degradation, veratric acid concentration and cell density in Rhodococcus
      erythropolis cultures. The optimum culture conditions for veratrate demethylation
      proved to be a cell density of A(660)=1 and a concentration of 0.02% veratrate.
      All the products of demethylation (i.e. vanillic and protocatechuic acids) were
      found to be present and correlated with the appearance of high levels of free
      radicals and formaldehyde after contact of the cells with veratrate.
      Demethylation was accompanied by oscillatory changes in the levels of endogenous
      oxygen uptake and phenolic products. Changes in veratrate concentration and cell
      density caused a disturbance in the demethylation process and also in the
      efficiency of phenolics, formaldehyde and reactive oxygen species.

PMID- 12788047
TI  - Runx transcription factors and the developmental balance between cell
      proliferation and differentiation.
AB  - The runt box (Runx) is a highly conserved DNA binding and protein-protein
      interaction domain that defines a family of heterodimeric transcription factors
      with essential roles in metazoan development. The first member of this family to
      be identified was the Drosophila regulatory gene runt, which was named by virtue
      of its function in establishing segmentation patterns during embryogenesis, and
      subsequently discovered to have additional functions in sex determination and
      neurogenesis. A second Drosophila Runx gene, lozenge, is required for cell
      patterning in the eye and for hematopoiesis. The genome project has revealed the
      existence of two additional Drosophila Runx genes, which to date have not been
      functionally characterized. Other invertebrate species with well-characterized
      Runx transcription factors include the nematode Caenorhabditis elegans and the
      sea urchin Strongylocentrotus purpuratus, each of which apparently contains only
      a single Runx gene. There are three Runx genes in mammals; Runx1 is required for
      definitive hematopoiesis and is a frequently mutated gene in human leukemia,
      Runx2 is required for osteogenesis and is associated with cleidocranial
      dysplasia, and Runx3 controls neurogenesis in the dorsal root ganglia and cell
      proliferation in the gastric epithelium, and is frequently deleted or silenced in
      human gastric cancer. Studies using mammalian systems and sea urchins indicate
      that Runx proteins have essential functions in both cell proliferation and
      differentiation, and in mammals they are both proto-oncogenes and tumor
      suppressors. Thus, a central question concerning the cell biology of Runx
      proteins is how are the opposing functions of this class of transcription factors
      regulated during development? Here I review current knowledge of Runx protein
      structure, function and regulation, and outline directions for future research
      aimed at understanding how Runx protein function is modulated during the
      transition from cell proliferation to differentiation in animal development.

PMID- 12788049
TI  - L-arginine and mitomycin C-induced nitric oxide release and apoptosis in human
      lymphocytes.
AB  - Nitric oxide (NO) is a free radical that is produced by a number of mammalian
      cell types from L-arginine and a critical mediator that acts in many tissues to
      regulate a diverse range of physiological processes. The major metabolic end
      product for NO is nitrate (NO(3)) and nitrite (NO(2)), which are stable
      metabolites within tissue, plasma, and urine. Measurements of nitrate and nitrite
      values reveal alterations in NO production. Endogenously generated or exogenously
      applied NO causes DNA cleavage by endonuclease activation. We investigated the
      effect of L-arginine and mitomycin C (MMC) on cultured lymphocytes of healthy
      individuals. We observed chromosome breaks, apoptotic cells and increased NO
      levels after L-arginine and MMC addition. In conclusion, our results confirmed
      that NO may be the cause of apoptotic cell death in L-arginine added lymphocyte
      culture.

PMID- 12788050
TI  - Inhibition of Ca2+/calmodulin-dependent protein kinase or epidermal growth factor
      receptor tyrosine kinase abolishes lysophosphatidic acid-mediated DNA-synthesis
      in human myometrial smooth muscle cells.
AB  - Human myometrial smooth muscle cells (SMCs) were used to evaluate the
      proliferative activity of lysophosphatidic acid (LPA). This study specifically
      focuses on the role of Ca(2+)/calmodulin-dependent protein (CaM) kinase and
      epidermal growth factor (EGF) receptor tyrosine kinase. Myometrial SMCs were
      cultured from biopsies taken at Cesarean sections. The expression of LPA
      receptors was determined by reverse transcriptase polymerase chain reaction (RT
      PCR), and DNA-synthesis was measured by [3H]thymidine incorporation. LPA(1),
      LPA(2), and LPA(3)receptor subtypes were detected in the SMCs using RT-PCR. KN
      62, an inhibitor of CaM kinase, and Tyrphostin AG 1478, an inhibitor of EGF
      receptor tyrosine kinase, dose-dependently decreased LPA-stimulated [3H]thymidine
      incorporation. Furthermore, BB-3103, an inhibitor of matrix metalloproteinases
      (MMPs), also reduced DNA-synthesis induced by LPA in these cells. The results
      show, for the first time, that human myometrial SMCs express all three known LPA
      receptor subtypes. Growth stimulatory effects of LPA on myometrial SMCs seems to
      be mediated by several pathways, where transactivation of EGF receptors through
      MMPs appears to be of importance. Furthermore, CaM kinase activity may be
      critical for LPA signaling since inhibition of CaM kinase totally abolish the
      proliferative effect of LPA.

PMID- 12788051
TI  - Flow cytometric cell-cycle analysis of cultured fibroblasts from the giant panda,
      Ailuropoda melanoleuca L.
AB  - In animal cloning, it is generally believed that the inactive diploid G(0)or
      G(1)stage of the cell cycle is beneficial to initiate cell-cycle coordination and
      reprogramming following transfer of the donor nucleus. Previous experiments have
      demonstrated that serum starvation results in quiescent cell stage. Some
      experiments show that the majority of cells in a fully confluent cell culture are
      also in an inactive G(1)stage. In order to provide more G(0)/G(1)stage cells for
      giant panda cloning, we carried out a flow cytometric analysis of the cell cycle
      of fibroblasts from the abdominal muscle of a giant panda at different passage
      numbers under different growth conditions, and after different periods of serum
      starvation. The percentage of G(0)+G(1)stage cells differed significantly under
      different growth conditions. Serum starvation effectively increased the
      percentage of G(0)+G(1)stage cells, and the cell cycle characteristics following
      serum starvation for varying periods of time differed with this and the initial
      confluency of the cultures. The data should help in choosing the optimal stage
      for preparing donor cells as well as increasing the potential cloning efficiency
      in our study of giant panda cloning.

PMID- 12788052
TI  - A microprobe study of element distribution in vaginal epithelial cells of the
      rat.
AB  - Microprobe analysis of vaginal epithelial cells shed during the estrous cycle of
      the rat was done to determine cellular elements present in successive stages: pro
      estrus, estrus, and post-estrus. Smears of vaginal contents were placed on carbon
      planchettes, fixed by freeze-drying, and examined in a scanning microscope with
      an energy dispersive spectrometer. Concentrations of Na, Mg, P, S, Cl, K, and Ca
      were calculated (mmol/kg dry weight) and analyzed statistically. For phosphorus a
      significant fall at estrus correlates with a loss of nuclear and cytoplasmic
      nucleic acids and nucleoproteins. An increase in sulfur at estrus is consistent
      with an accumulation of keratins over pro-estrus and a greater increase over the
      post-estrus epithelial cells. The epithelial cells of pro-estrus are highest in
      Mg and Ca. By post-estrus, the cells have recovered their Mg, not Ca. Potassium
      concentrations exhibited no significant change between the successive stages.

PMID- 12788053
TI  - Spatio-temporal expression of Drosophila mitochondrial transcription factor A
      during development.
AB  - We previously reported cloning of the Drosophila mitochondrial transcription
      factor A (D-mtTFA) gene, and characterization of a recombinant protein. In this
      report, the expression and distribution patterns of D-mtTFA during development
      are described. D-mtTFA mRNA and its protein product were found to be abundant in
      cells of tissues undergoing both proliferation and polytenization. Furthermore, a
      DRE-like sequence present in the D-mtTFA gene showed promotor activity in
      Drosophila Kc cells. In addition, D-mtTFA was detected in brain throughout the
      developmental process, as well as in non-proliferating tissues, such as flight
      muscle and cardia, and was also found in spermatids of imagos. D-mtTFA possesses
      a nuclear-targeting sequence, and is present in the nucleus at the syncytial
      stage, where bundles of 64 spermatids are present during spermatogenesis. The
      results suggest that D-mtTFA not only contributes to the mitochondrial DNA
      transcription and replication system, but also has a role in cell proliferation
      and development, including spermatogenesis.

PMID- 12788054
TI  - Targeting apoptotic signalling pathway and pro-inflammatory cytokine expression
      as therapeutic intervention in TPE induced lung damage.
AB  - Tropical pulmonary eosinophilia (TPE) is an occult manifestation of filariasis,
      brought about by helminth parasites Wuchereria bancrofti and Brugia malayi.
      Treatment of patients suffering from TPE involves the administration of diethyl
      carbamazine and Ivermectin. Although the drugs are able to block acute
      inflammation, they are not able to alleviate chronic basal inflammation. We have
      attempted to examine the disease by targeting two important components; namely
      filarial parasitic sheath proteins (FPP) induced apoptosis and pro-inflammatory
      cytokine response in human laryngeal carcinoma cells of epithelial origin (HEp-2)
      cells an epithelial cell line. Earlier studies by us have shown that FPP exposure
      induced apoptosis in these cells. In this study with hydrocortisone, calpain
      inhibitor (ALLN) and phorbol myristate acetate (PMA) treatments we demonstrate
      that apoptosis is inhibited as shown by [3H] thymidine incorporation studies,
      propidium iodide staining and Annexin V staining. Hydrocortisone at a dose, which
      inhibits cell death also down regulated, the expression of pro-inflammatory
      cytokines IL-6 and IL-8. These findings give us insights into the multifaceted
      approach one may adopt to target critical signalling molecules using appropriate
      inhibitors, which could eventually be used to reduce lung damage in TPE.

PMID- 12788055
TI  - Chronobiology of the proliferative events related to angiogenesis in mice liver
      regeneration after partial hepatectomy.
AB  - In liver regeneration the formation of new capillary blood vessels is a
      fundamental requirement for cellular proliferation. Vascular endothelial growth
      factor (VEGF) is involved in the events of angiogenesis, the mRNA of which is
      expressed in both hepatocytes and non-parenchymal cells. In this experimental
      design we try to establish if during liver regeneration in mouse, the expression
      of VEGF is produced before or after the hepatocytes proliferation. C3H/S adult
      male mice were divided in three groups in order to study: VEGF expression; S
      phase index (SI); and mitotic activity (MA) of hepatocytes. The results that were
      analyzed by ANOVA, show that VEGF expression starts to increase 26 h after PH
      with a peak at 28 h. Furthermore, the DNA synthesis (DNAs) reaches maximal level
      42 h after pH, meanwhile the MA of the hepatocytes shows an increase 8h after the
      DNAs peak. In conclusion, it could be argued that the chronobiology of the events
      related to liver regeneration in mice started with a release of VEGF by the
      hepatocytes, followed by its DNAs and mitosis.

PMID- 12788056
TI  - Gender differences in the histamine and serotonin content of blood, peritoneal
      and thymic cells: a comparison with mast cells.
AB  - The serotonin and histamine content of mast cells and white blood cells in adult
      male and female rats was compared, using a flow cytometric immunological method.
      Serotonin was significantly higher in female peritoneal mast cells, peritoneal
      monocyte-ganulocyte-macrophage cells, blood lymphocytes and blood thymocytes.
      Histamine was significantly higher in female peritoneal monocyte-granulocyte
      macrophage cells, and blood lymphocytes, monocytes and granulocytes, but was
      significantly less in thymocytes. Peritoneal lymphocytes and the monocyte
      granulocyte-macrophage group contained significantly more histamine than mast
      cells. These experiments call attention to gender differences in the levels of
      biogenic amines in cells participating in defence reactions, and to the possible
      non-unique role of mast cells in serotonin and histamine supply.

PMID- 12788057
TI  - DNA binding of nuclear hormone receptors influences their structure and function.

PMID- 12788058
TI  - Genome-wide expression analysis of NAP1 in Saccharomyces cerevisiae.
AB  - Nap1 is a nucleosome assembly protein which is necessary to keep proper
      nucleosome structures in transcription and replication in vitro. In Saccharomyces
      cerevisiae, additional functions have been ascribed to Nap1, as it has been shown
      to interact with Clb2 (B type cyclin) and Gin4 (septum formation). In this study,
      we investigate genome-wide expression in the Deltanap1 cells using DNA
      microarrays. About 10% of all yeast open reading frames changed the transcription
      level more than 2-fold in the Deltanap1 strain, compared with wild-type strain,
      in one experiment. Interestingly, these genes, whose expressions are up- or down
      regulated in the Deltanap1 cells, are clustered. This result suggests that yeast
      NAP1 is required for the maintenance of cumulative nucleosome formation in vivo
      and the loss of Nap1 leads to a change in the gene expression level in a cluster.

PMID- 12788059
TI  - Adrenomedullin augments collateral development in response to acute ischemia.
AB  - Expression of adrenomedullin, discovered as a vasodilatory peptide, is markedly
      up-regulated under pathological conditions such as tissue ischemia and
      inflammation, which are associated with neovascularization. Here, we tested the
      hypothesis that overly expressed adrenomedullin may augment collateral flow to
      ischemic tissues. We induced hindlimb ischemia in wild-type mice and injected a
      naked plasmid expressing human adrenomedullin or an empty vector into the
      ischemic muscle, followed by in vivo electroporation. Adrenomedullin markedly
      enhanced blood flow recovery as determined by Laser Doppler imaging. The mice
      treated with an empty vector suffered frequent autoamputation of the ischemic
      toe, which was completely prevented by adrenomedullin. Anti-CD31 immunostaining
      revealed that adrenomedullin significantly increased capillary density. The
      angiogenic effect of adrenomedullin was abrogated in endothelial nitric oxide
      synthase (eNOS)-deficient mice. These results indicate that adrenomedullin may
      promote collateral growth in response to ischemia through activation of eNOS.

PMID- 12788060
TI  - Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a
      novel tumor marker.
AB  - With the global pandemic of hepatitis B and C infections, the incidence of
      Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified
      glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human
      HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane
      protein and could be secreted, we attempted to detect secreted GPC3 protein in
      sera from HCC patients using Western blotting and ELISA. GPC3 protein was
      positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from
      subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and
      healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients
      were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor
      markers of HCC, four of these were GPC3-positive in the sera. We also observed
      vanishing GPC3 protein in the sera of three patients after the surgical treatment
      for HCC. On the other hand, immunohistochemical analysis revealed that HCC
      expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as
      defined in this study was shown to be a useful tumor marker for cancer-diagnosis
      for large numbers of patients with HCC.

PMID- 12788061
TI  - Triphenyltin enhances the neutrophilic differentiation of promyelocytic HL-60
      cells.
AB  - Triphenyltin (TPT) is an environmental endocrine disruptor and toxic substance,
      but little information is available on its immunological effects. To assess the
      effect of TPT on leukocyte differentiation, we investigated its effect on the
      neutrophilic differentiation of HL-60 cells induced by dimethyl sulfoxide and
      granulocyte colony-stimulating factor (G-CSF) for 6 days. At a low concentration,
      10(-7)M, TPT increased superoxide production by differentiated HL-60 cells
      stimulated with opsonized zymosan (OZ) by about 45% and increased expression of
      CD18, a component of the OZ-receptor, by about 90%. Real-time PCR analysis
      revealed that TPT augmented the expression not only of CD18 but also of
      components of superoxide-generating NADPH-oxidase, p47phox, 2.7-fold, and
      p67phox, 2.0-fold, and of granulocyte colony-stimulating factor receptor (G
      CSFR), 3.0-fold, whereas various other endocrine disruptors, including parathion,
      vinclozolin, and bisphenol A, had no such enhancing effects. The results of a DNA
      macroarray analysis showed that TPT enhanced the expression of G-CSFR and certain
      other neutrophil functional proteins, including CD14 and myeloid leukemia cell
      differentiation protein (MCL-1), and that TPT induced a decrease in expression of
      LC-PTP, leukocyte protein-tyrosine phosphatase, to about half the control level.
      The TPT-dependent suppression of LC-PTP was confirmed by real-time PCR analysis,
      and the results of immunoblotting indicated that TPT enhances the expression of
      myeloid specific tyrosine kinase hck by about 30% at the protein level, and this
      together with the reduction of LC-PTP may enhance tyrosine phosphorylation, in
      turn resulting in enhancement of superoxide production. These findings suggest
      that TPT may have an enhancing effect on the neutrophilic maturation of
      leukocytes.

PMID- 12788062
TI  - Serum response factor is modulated by the SUMO-1 conjugation system.
AB  - Serum stimulation leads to activation of the serum response factor (SRF)-mediated
      transcription of immediate-early genes such as c-fos via various signal
      transduction pathways. We have previously reported that promyelocytic leukemia
      protein (PML) is involved in the transcriptional regulation by SRF. PML is one of
      the well-known substrates for modification by small ubiquitin-related modifier-1
      (SUMO-1) and several SUMO-1-modified proteins associate with PML. Here, we report
      that SRF is modified by SUMO-1 chiefly at lysine(147) within the DNA-binding
      domain. Substitution of this target lysine for alanine did not affect the
      translocation of SRF to PML-nuclear bodies. The SRF mutant augmented the
      transcriptional activity under Rho A-stimulated condition but not under serum
      starved condition, suggesting that activated SRF is suppressed by its
      sumoylation. These data support the transcriptional role of SUMO-1 conjugating
      system in cellular serum response.

PMID- 12788063
TI  - Refolding of partially thermo-unfolded cinnamomin A-chain mediated by B-chain.
AB  - The pure cinnamomin A-chain is unstable compared to that in the mixture of A- and
      B-chain or in intact cinnamomin molecule either being stored at 4 degrees C or
      being heated. When being heated at 45 degrees C for 20min, the A-chain generates
      partially unfolded intermediate and loses its tertiary structure as monitored by
      circular dichroism (CD) and tryptophan fluorescence, thus resulting in the
      inactivity of its RNA N-glycosidase albeit it retains most of its secondary
      structures. This partially unfolded intermediate is sensitive to protease,
      exhibiting property of a molten globule. The changes in conformation and activity
      are irreversible upon cooling. The partially unfolded intermediate can fully
      restore its RNA N-glycosidase activity in the presence of cinnamomin B-chain. The
      phenomenon, that the cinnamomin B-chain mediates the refolding of partially
      unfolded A-chain, probably plays an important role in the intracellular transport
      of the cytotoxic protein, i.e., keeping the structural stability of A-chain and
      refolding partially unfolded A-chain that occasionally appeared in the process of
      intracellular transport, to avoid the destiny of proteolysis that occurs in most
      denatured proteins in cell.

PMID- 12788064
TI  - Implications of a polyglutamine tract in the function of the human androgen
      receptor.
AB  - The androgen receptor (AR) is a ligand-dependent transcription factor and belongs
      to the nuclear receptor family. The AR gene contains a long polymorphic CAG
      repeat, coding for a polyglutamine tract. In the full size AR, the deletion of
      the polyglutamine tract results in an increase in the transactivation through
      canonical AREs. However, this effect is clearly dependent on the response
      elements, since it is not observed on selective elements. In our assays, a
      deletion of the repeat positively affected the interactions of the ligand-binding
      domain with the amino-terminal domain as well as the recruitment of the p160
      coactivator SRC-1e to the amino-terminal domain of the AR. This is reflected by
      an enhanced coactivation of the AR by SRC-1e.

PMID- 12788065
TI  - Visualization of the reconstituted FRGY2-mRNA complexes by electron microscopy.
AB  - Xenopus oocytes store large quantities of translationally dormant mRNA in the
      cytoplasm as storage messenger ribonucleoprotein particles (mRNPs). The Y-box
      proteins, mRNP3 and FRGY2/mRNP4, are major RNA binding components of maternal
      storage mRNPs in oocytes. In this study, we show that the FRGY2 proteins form
      complexes with mRNA, which leads to mRNA stabilization and translational
      repression. Visualization of the FRGY2-mRNA complexes by electron microscopy
      reveals that FRGY2 packages mRNA into a compact RNP. Our results are consistent
      with a model that the Y-box proteins function in packaging of mRNAs to store them
      stably for a long time in the oocyte cytoplasm.

PMID- 12788066
TI  - Reversible folding of cysteine-rich metallothionein by an overcritical reaction
      path.
AB  - A first-order-like state transition is considered to be involved in the
      restoration of the activities of a few proteins by correctly folding the protein
      [Phys. Rev. E 66 (2002) 021903]. In order to understand the general applicability
      of this mechanism, we studied a metallothionein (MT) protein with an
      unconventional structure, i.e., without any alpha-helix or beta-sheet. MT is a 61
      amino-acid peptide. There are 6-7 Zn(2+) ions, which bind avidly to 20 conserved
      cysteines (Cys) of MT. These properties indicate that the structure of MT is
      quite different from those of the other proteins. Similar to our previous
      findings, the denatured MT can be folded without any aggregation via a designated
      stepwise quasi-static process (an over-critical reaction path). The particle size
      of folded MT intermediates, determined by dynamic light scattering, shrank right
      after the first folding stage. It is consistent with a collapse-model. In
      addition, results from both atomic absorption and circular dichroism (CD)
      indicate that the stable intermediates may fold to the native conformation but
      with only partial Zn(2+) binding, which in turn implies that those folding
      intermediates are in a molten globular state. These reversible unfolding and
      folding processes indicate that Cys-rich protein, MT, may also be folded by way
      of a first-order-like state transition mechanism. We suspect that this process
      may likely be involved in the reaction of the metal substitution process in metal
      containing enzymes.

PMID- 12788067
TI  - Molecular cloning and characterization of human, rat, and mouse synaptotagmin XV.
AB  - Synaptotagmin (Syt) constitutes a large family of putative membrane trafficking
      proteins that share a short extracellular domain, a single N-terminal
      transmembrane domain, and C-terminal tandem C2 domains. In this study, I
      identified and characterized a novel member of the Syt family (named Syt XV-a) in
      the mouse, the rat, and humans. Although Syt XV-a protein has a short hydrophobic
      region at the very end of the N terminus (i.e., lacks a putative extracellular
      domain), biochemical and cellular analyses have indicated that the short
      hydrophobic region (amino acids 5-22) is sufficient for producing type I membrane
      topology in cultured cells, the same as in other Syt family proteins. Unlike
      other Syt isoforms, however, the mouse and human Syt XV have an alternative
      splicing isoform that lacks the C-terminal portion of the C2B domain (named Syt
      XV-b). Since the expression of Syt XV-a/b mRNA was mainly found in non-neuronal
      tissues (e.g., lung and testis) and Syt XV-a C2 domains lack Ca(2+)-dependent
      phospholipid binding activity, Syt XV-a is classified as a non-neuronal, Ca(2+)
      independent Syt.

PMID- 12788068
TI  - Mechanism of nucleosome disruption and octamer transfer by the chicken SWI/SNF
      like complex.
AB  - We had recently characterized SLC, a SWI/SNF-like chromatin remodelling activity,
      from chicken liver. The SLC efficiently disrupts nucleosomes, transfers histone
      octamers from nucleosomal substrates onto acceptor DNA, and slides histone
      octamers along DNA. Here, we present evidence that SLC is indeed a SWI/SNF
      homologue, and it disrupts nucleosomes by inducing extensive dynamic helical
      distortions in the nucleosomal DNA. Both the nucleosome disruption and octamer
      transfer functions are indifferent to nucleosomal histone tails. We further show
      that the nucleosome disruption precedes the octamer transfer and that the latter
      requires continuous presence of ATP. Based on these observations, we propose that
      a disrupted nucleosome is not a spontaneous substrate for octamer transfer;
      rather the nucleosome disruption and the octamer transfer are two temporally
      successive, ATP-dependent events during nucleosome remodelling by SLC in vitro.

PMID- 12788069
TI  - MICAL-1 isoforms, novel rab1 interacting proteins.
AB  - Rab1 GTPases participate in regulating the vesicular transport of ER-Golgi
      compartments. Recently, GM130, p115, and Golgin-84 were identified as effectors
      of the active conformation of rab1. Here, we describe a novel protein, MICAL-1b,
      a splice variant of the MICAL-1a protein. Using the yeast two-hybrid system, we
      showed that it specifically interacts with rab1 in a nucleotide-dependent manner.
      The interaction was confirmed by GST pulldown experiments. Cell fractionation
      revealed that in contrast to the mainly membrane-associated rab1 effector GM130,
      MICAL-1 displays a predominantly cytosolic localization. We mapped the rab1
      interacting domain to the C-terminus of MICAL-1, which also mediates binding to
      the intermediate filament vimentin. Therefore, the interaction of MICAL-1 and
      rab1 might provide a link between the Golgi apparatus and the intermediate
      filament cytoskeleton. We suggest that MICAL-1 isoforms with their multidomain
      structure are novel rab1 interacting proteins that function as scaffold proteins
      connecting different components in the cell.

PMID- 12788070
TI  - DNA cleavage characteristics of non-protein enediyne antibiotic N1999A2.
AB  - N1999A2 (NA2) is a new non-protein antitumor antibiotic that contains a stable 9
      membered ring enediyne chromophore similar to a neocarzinostatin chromophore (NCS
      chr). We have compared DNA cleavage reactions between NA2 and NCS-chr, and also
      clarified some characteristics of DNA strand scission by NA2. It was found that:
      (1) NA2 is considerably stable in nature, (2) the compound intercalates into base
      pairs of a DNA minor groove and decreases its base-attacking frequency in the
      order of T>A>> C>G, (3) the base-sequence specificity 5(')-GGT/3(')-CCA presented
      by NA2 is significantly related to recognition of the base pair with the
      naphthoate moiety, and (4) the different cleavage property between NCS-chr and
      NA2 is associated with the presence or absence of an aminoglycoside residue.
      Based on the results of the site-specific cleavage by NA2 for certain bulged DNAs
      and a fluorescence study of NA2-DNA oligomer complexes, the DNA interaction mode
      of NA2 has also been examined. These results provide important information to
      design a new enediyne molecule for a DNA target.

PMID- 12788071
TI  - Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye
      brain disease.
AB  - Muscle-eye-brain disease (MEB), an autosomal recessive disorder, is characterized
      by congenital muscular dystrophy, brain malformation, and ocular abnormalities.
      Previously, we found that MEB is caused by mutations in the gene encoding the
      protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1),
      which is responsible for the formation of the GlcNAcbeta1-2Man linkage of O
      mannosyl glycan. Although 13 mutations have been identified in patients with MEB,
      only the protein with the most frequently observed splicing site mutation has
      been studied. This protein was found to have no activity. Here, we expressed the
      remaining mutant POMGnT1s and found that none of them had any activity. These
      results clearly demonstrate that MEB is inherited as a loss-of-function of
      POMGnT1.

PMID- 12788072
TI  - New functions of lactoferrin and beta-casein in mammalian milk as cysteine
      protease inhibitors.
AB  - We found new inhibitory function of lactoferrin and beta-casein in milk against
      cysteine proteases using reverse zymography. The inhibition of cathepsin L by
      lactoferrin was strongest and the inhibition kinetics were of a non-competitive
      type. Heat denatured lactoferrin lost the inhibitory activity completely,
      therefore the tertiary structure is essential to show the inhibition. Native
      lactoferrin was not degraded by papain during the assay condition. The
      intramolecular peptide, Y(679)-K(695), of lactoferrin is an active domain and the
      synthesized peptide inhibited cysteine proteases. The Y(679)-K(695) peptide
      showed 90% homology with the sequences of a common active site of cystatin
      family. beta-Casein and the active domain, synthesized L(133)-Q(151), peptide
      inhibited cysteine proteases. Lactoferrin and beta-casein in milk might play a
      role in antiseptic and antiinfectious functions due to cysteine protease
      inhibition of bacteria and viruses.

PMID- 12788073
TI  - Regulation by nectin of the velocity of the formation of adherens junctions and
      tight junctions.
AB  - Cadherins are key Ca(2+)-dependent cell-cell adhesion molecules at adherens
      junctions (AJs) in fibroblasts and epithelial cells, whereas claudins are key
      Ca(2+)-independent cell-cell adhesion molecules at tight junctions (TJs) in
      epithelial cells. The formation and maintenance of TJs are dependent on the
      formation and maintenance of AJs. Nectins are Ca(2+)-independent immunoglobulin
      like cell-cell adhesion molecules which comprise a family of four members, nectin
      1, -2, -3, and -4, and are involved in the formation of AJs in cooperation with
      cadherins, and the subsequent formation of TJs. We show here that the velocity of
      the formation of the E-cadherin-based AJs is increased by overexpression of
      nectin-1 and is reduced by addition of the nectin-1 inhibitors to the medium in L
      cells stably expressing E-cadherin and Madin-Darby canine kidney cells. Moreover,
      the velocity of the formation of the claudin-based TJs is increased by
      overexpression of nectin-1 and is reduced by addition of the nectin-1 inhibitors
      to the medium in Madin-Darby canine kidney cells. These results indicate that
      nectins regulate the velocity of the formation of the E-cadherin-based AJs and
      the subsequent formation of the claudin-based TJs.

PMID- 12788074
TI  - ATP-citrate lyase as a substrate of protein histidine phosphatase in vertebrates.
AB  - The first protein histidine phosphatase from vertebrates discovered recently was
      found in a variety of tissues, however, a physiological substrate protein was
      missing. Phosphorylation of liver extracts in the presence of EDTA, followed by
      SDS-PAGE and autoradiography showed labeling of three proteins. Acid- and
      alkaline-treatment revealed the existence of N-phosphates. Addition of histidine
      phosphatase exclusively resulted in dephosphorylation of a 110kDa protein
      (denaturing conditions). Gelfiltration revealed its native molecular mass of
      approximately 450kDa. That protein was purified and identified as ATP-citrate
      lyase. The results are in favor of histidine phosphatase playing an important yet
      unidentified role in metabolic processes.

PMID- 12788075
TI  - Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and
      simultaneously down-regulates steroid xenobiotic receptor mRNA.
AB  - A steroid xenobiotic receptor (SXR) is involved in the induction of MDR1/P
      glycoprotein. MDR1 up-regulation by digoxin was previously demonstrated in human
      colon adenocarcinoma Caco-2 cells, but the participation of SXR remains unclear.
      Herein, the participation of SXR in MDR1 up-regulation was examined using reverse
      transcription-polymerase chain reaction in Caco-2 cells, and digoxin-tolerant
      cells (Caco/DX) as well as human colon carcinoma LS180 cells, which expressed
      SXR. MDR1 mRNA expression in Caco-2 or LS180 cells was increased by exposure to 1
      microM digoxin for 24h, in a concentration-dependent manner, but SXR mRNA
      decreased concentration-dependently and was undetectable or significantly lower
      at 1 microM digoxin, indicating antithetical changes in MDR1 and SXR mRNA
      expression. Moreover, the MDR1 mRNA level was higher in Caco/DX cells than Caco-2
      cells, whereas the SXR mRNA level was lower in Caco/DX cells. Consequently,
      digoxin was demonstrated to up-regulate MDR1 mRNA and simultaneously down
      regulate SXR mRNA expression.

PMID- 12788076
TI  - Characterization of organic cation/carnitine transporter family in human sperm.
AB  - Spermatozoan maturation, motility, and fertility are, in part, dependent upon the
      progressive increase in epididymal and spermatozoal carnitine, critical for
      mitochondrial fatty acid oxidation, as sperm pass from the caput to the cauda of
      the epididymis. We demonstrate that the organic cation/carnitine transporters,
      OCTN1, OCTN2, and OCTN3, are expressed in sperm as three distinct proteins with
      an expected molecular mass of 63 kDa, using Western blot analysis and our
      transporter-specific antibodies. Carnitine uptake studies in normal control human
      sperm samples further support the presence of high-affinity (OCTN2) carnitine
      uptake (K(m) of 3.39+/-1.16 microM; V(max) of 0.23+/-0.14 pmol/min/mg sperm
      protein; and mean+/-SD; n=12), intermediate-affinity (OCTN3) carnitine uptake
      (K(m) of 25.9+/-14.7 microM; V(max) of 1.49+/-1.03 pmol/min/mg protein; n=26),
      and low-affinity (OCTN1) carnitine uptake (K(m) of 412.6+/-191 microM; V(max) of
      32.7+/-20.5 pmol/min/mg protein; n=18). Identification of individuals with
      defective sperm carnitine transport may provide potentially treatable etiologies
      of male infertility, responsive to L-carnitine supplementation.

PMID- 12788077
TI  - Selectivity of 4,5,6,7-tetrabromobenzimidazole as an ATP-competitive potent
      inhibitor of protein kinase CK2 from various sources.
AB  - Like the previously reported 4,5,6,7-tetrabromobenzotriazole (TBBt), the
      structurally related 4,5,6,7-tetrabromobenzimidazole (TBBz) is a selective ATP
      competitive inhibitor of protein kinase CK2 from such divergent sources as yeast,
      rat liver, Neurospora crassa and Candida tropicalis, with K(i) values in the
      range 0.5-1 microM. It is virtually inactive vs. PKA, PKC, and a very weak
      inhibitor of protein kinase CK1. The corresponding tetrachlorobenzimidazole
      (TCBz) is a much weaker inhibitor of CK2, like tetrachlorobenzotriazole (TCBt)
      relative to TBBt. Bearing in mind the similarity of the van der Waals radii of Br
      (1.95 A) and CH(3) (2.0 A), the corresponding much less hydrophobic 4,5,6,7
      tetramethylbenzotriazole (TMeBt) was prepared and found to be a very weak
      inhibitor of CK2, as well as of CK1. An unexpected, and significant, difference
      between TBBt and TBBz are their inhibitory activities vs. the yeast protein
      kinase PK60S, which phosphorylates, both in vitro and in intact yeast cells,
      three of the five pp13 kDa ribosomal surface acidic proteins in yeast cells. TBBt
      was previously noted to be a more effective inhibitor of PK60S than of yeast CK2;
      by contrast, TBBz is a relatively feeble inhibitor of PK60S, hence more selective
      than TBBt vs. CK2 in yeast cells. TMeBt was virtually inactive vs PK60S. Like
      TBBt, TBBz is an additional lead compound for development of more potent
      inhibitors of CK2.

PMID- 12788078
TI  - The 10trans,12cis isomer of conjugated linoleic acid suppresses the development
      of hypertension in Otsuka Long-Evans Tokushima fatty rats.
AB  - Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers
      of linoleic acid found in beef, lamb, and dairy products. CLA has attracted
      considerable attention over the past several decades because of its potentially
      beneficial biological effects, including protective effects against several
      cancers, atherosclerosis, and obesity. Here we provide the first evidence that
      the 10trans,12cis-CLA isomer is able to suppress increases in blood pressure
      during the onset of obesity in OLETF rats. After 3 weeks of feeding with 10t,12c
      CLA, systolic blood pressure was significantly lowered compared with rats fed
      linoleic acid or 9c,11t-CLA. Abdominal adipose tissue weight was also
      significantly lowered in rats fed 10t,12c-CLA, but not in those which were fed
      9c,11t-CLA. In addition, we found that the relative mRNA expressions of
      angiotensinogen and leptin were suppressed by 10t,12c-CLA in adipose tissue. We
      speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to
      the lowered secretion of hypertensive adipocytokines from abdominal adipose
      tissues.

PMID- 12788079
TI  - TNF-alpha and leptin activate the alpha-isoform of class II phosphoinositide 3
      kinase.
AB  - The class II PI 3-kinases are known to be activated by growth factors and
      chemokines but to date there are no reports of cytokine mediated regulation.
      Further, the intracellular signalling mechanisms regulating the class-II PI 3
      kinases are poorly understood. We investigated the effects of the cytokines
      TNFalpha and leptin on the activity of the alpha isoform of the class II PI 3
      kinase (PI3K-C2alpha) and find that these stimulate the enzyme 2-fold and 3-fold,
      in CHO cells and J774.2 macrophages, respectively. The stimulation by leptin was
      not accompanied by recruitment of any tyrosine phosphorylated proteins to PI3K
      C2alpha and no shift in electrophoretic mobility was noted. Furthermore, we
      demonstrate that the actions of both cytokines are blocked by the MEK inhibitor
      PD98059. These findings indicate that the cytokines activate PI3K-C2alpha and do
      so by a mechanism that requires activation of the ERK pathway and thus differs
      from the mechanism used by insulin to activate the enzyme.

PMID- 12788080
TI  - Parathyroid hormone induces the nuclear orphan receptor NOR-1 in osteoblasts.
AB  - Parathyroid hormone (PTH) significantly affects osteoblast function by altering
      gene expression. We have identified neuron-derived orphan receptor-1 (NOR-1) as a
      PTH-induced primary gene in osteoblastic cells. NOR-1, Nurr1, and Nur77 comprise
      the NGFI-B nuclear orphan receptor family and Nurr1 and Nur77 are PTH-induced
      primary osteoblastic genes. Ten nM PTH maximally induced NOR-1 mRNA at 2h in
      primary mouse osteoblasts and at 1h in mouse calvariae. Cycloheximide
      pretreatment did not inhibit PTH-induced NOR-1 mRNA. PTH activates cAMP-protein
      kinase A (PKA), protein kinase C (PKC), and calcium signaling. Forskolin (PKA
      activator) and PMA (PKC activator) mimicked PTH-induced NOR-1 mRNA. Ionomycin
      (calcium ionophore) and PTH(3-34), which do not activate PKA, failed to induce
      NOR-1 mRNA. PKA inhibition with H89 blocked PTH- and FSK-induced NOR-1 mRNA. PMA
      pretreatment to deplete PKC inhibited PMA-induced, but not PTH-induced, NOR-1
      mRNA. We conclude that NOR-1 is a PTH-regulated primary osteoblastic gene that is
      induced mainly through cAMP-PKA signaling.

PMID- 12788081
TI  - p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn.
AB  - Fyn is a member of the Src-family protein tyrosine kinases and plays important
      roles in both neurons and oligodendrocytes. Here we report association of Fyn
      with p250GAP, a RhoGAP protein that is expressed predominantly in brain. p250GAP
      interacts with Fyn both in vitro and in vivo. p250GAP is tyrosine phosphorylated
      by Fyn when co-expressed in HEK293T cells. This phosphorylation appears to
      enhance the interaction between p250GAP and Fyn. Furthermore, the level of
      tyrosine phosphorylation of p250GAP increases upon differentiation of the
      oligodendrocyte cell line CG4. Given that Fyn activity is up-regulated during
      oligodendrocyte maturation, the results argue that p250GAP is phosphorylated by
      Fyn in oligodendrocytes. Tyrosine phosphorylation of p250GAP by Fyn would
      regulate its RhoGAP activity, subcellular localization, or interactions with
      other proteins, leading to morphological and phenotypic changes of
      oligodendrocytes.

PMID- 12788082
TI  - Properties and regulation of glutamine transporter SN1 by protein kinases SGK and
      PKB.
AB  - The amino acid transporter SN1 with substrate specificity identical to the amino
      acid transport system N is expressed mainly in astrocytes and hepatocytes where
      it accomplishes Na(+)-coupled glutamine uptake and efflux. To characterize
      properties and regulation of SN1, substrate-induced currents and/or radioactive
      glutamine uptake were determined in Xenopus oocytes injected with cRNA encoding
      SN1, the ubiquitin ligase Nedd4-2, and/or the constitutively active serum and
      glucocorticoid inducible kinase S422DSGK1, its isoform SGK3, and the
      constitutively active protein kinase B T308D,S473DPKB. The substrate-induced
      currents were enhanced by increasing glutamine and/or Na(+) concentrations,
      hyperpolarization, and alkalinization (pH 8.0). They were inhibited by
      acidification (pH 6.0). Coexpression of Nedd4-2 downregulated SN1-mediated
      transport, an effect reversed by coexpression of S422DSGK1, SGK3, and
      T308D,S473DPKB. It is concluded that SN1 is a target for the ubiquitin ligase
      Nedd4-2, which is inactivated by the serum and glucocorticoid inducible kinase
      SGK1, its isoform SGK3, and protein kinase B.

PMID- 12788083
TI  - ERK6 is expressed in a developmentally regulated manner in rodent skeletal
      muscle.
AB  - Rat ERK6, also known as SAPK3 and p38gamma, exhibits a distinct pattern of
      expression during muscle development in vitro and in vivo. Levels of mRNA
      transcript and protein abundance for ERK6 are increased during the
      differentiation of 2 rodent myoblast cell lines in culture. This is in contrast
      to the expression of other MAP kinase family members, namely p42/p44 MAPK and p38
      MAPK, whose expression does not change during myogenesis. Similar results are
      observed in vivo where ERK6 mRNA levels increase with post-natal development in
      rat hindlimb mixed muscle samples. These results delineate a distinct pattern of
      ERK6 expression in mature skeletal muscle cells and suggest a specific role for
      ERK6 in muscle development or muscle function.

PMID- 12788084
TI  - Existence of catalase-less peroxisomes in Sf21 insect cells.
AB  - Catalase activity, a peroxisomal marker enzyme, was not detectable in any of the
      subcellular fractions of Spodoptera frugiperda (Sf) 21 insect cells, although
      marker enzymes in other organelles were distributed in the fractions in a manner
      similar to that seen in mammalian cells. When a green fluorescent protein fused
      with peroxisome targeting signal 1 at the C-terminal (GFP-SKL) was expressed in
      Sf21 cells, punctate fluorescent dots were observed in the cytoplasm. The
      fraction where GFP-SKL was concentrated exhibited long-chain and very-long-chain
      fatty acid beta-oxidation activities in the presence of KCN and the density of
      this fraction was slightly higher than that of mitochondria. Immunoelectron
      microscopy studies with anti-SKL antibody demonstrated that Sf21 cells have
      immunoreactive peroxisome-like organelles which are structurally distinct from
      mitochondria, endoplasmic reticulum, and lysosomes. In contrast to peroxisomal
      matrix proteins, adrenoleukodystrophy protein, a peroxisomal membrane protein,
      was not located to peroxisomes. This suggests that the targeting signal for PMP
      in insect cells is distinct from that in mammalian cells. These results
      demonstrate that Sf21 insect cells have unique catalase-less peroxisomes capable
      of beta-oxidation of fatty acids.

PMID- 12788085
TI  - Transmembrane segment 5 of the dipeptide transporter hPepT1 forms a part of the
      substrate translocation pathway.
AB  - This study is the first systematic attempt to investigate the role of
      transmembrane segment 5 of hPepT1, the most conserved segment across different
      species, in forming a part of the aqueous substrate translocation pathway. We
      used cysteine-scanning mutagenesis in conjunction with the sulfhydryl-specific
      reagents, MTSEA and MTSET. Neither of these reagents reduced wild-type-hPepT1
      transport activity in HEK293 cells and Xenopus oocytes. Twenty-one single
      cysteine mutations in hPepT1 were created by replacing each residue within TMS5
      with a cysteine. HEK293 cells were then transfected with each mutated protein and
      the steady-state protein level, [3H]Gly-Sar uptake activity, and sensitivity to
      the MTS reagents were measured. S164C-, L168C-, G173C-, and I179C-hPepT1 were not
      expressed on the plasma membrane. Y167C-, N171C-, and S174C-hPepT1 showed </=25%
      Gly-Sar uptake when compared with WT-hPepT1. P182C-hPepT1 showed approximately
      40% specific activity whereas all the remaining transporters, although still
      sensitive to single cysteine mutations, exhibited more than 50% specific activity
      when compared to WT-hPepT1. The activity of F166C-, L176C-, S177C-, T178C-, I180C
      , T181C-, and P182C-hPepT1 was partially inhibited, while the activity of F163C-
      and I170C-hPepT1 was completely inhibited by 2.5mM MTSEA. F163C, I165C, F166C,
      A169C, I170C, S177C, T181C, and P182C were clearly accessible to 1mM MTSET.
      Overall, these results suggest that TMS5 lines the putative aqueous channel and
      is slightly tilted from the vertical axis of the channel, with the exofacial half
      forming a classical amphipathic alpha-helix and the cytoplasmic half being highly
      solvent accessible.

PMID- 12788086
TI  - Thyroxine downregulates Sox9 and promotes chondrocyte hypertrophy.
AB  - Thyroid hormones exert a profound effect on development, growth, and metabolism
      of skeleton. In the present study, we evaluated the effects of thyroxine (T4) and
      growth hormone (GH) on the terminal differentiation of rib growth plate
      chondrocytes in three-dimensional pellet culture. T4 (30ng/ml) stimulated the
      expressions of type II and X collagens, alkaline phosphatase (ALP) activity. On
      the other hand, the expression of chondrogenic transcription factor Sox9 in the
      T4 treatment group decreased significantly compared to the control group. T4
      downregulates Sox9 and promotes hypertrophy. After day 7, T4 increases
      dramatically the synthesis of type X collagen mRNA, ALP activity, and cellular
      hypertrophy. Addition of GH does not modify the action of T4. Thus, T4 acts
      directly on chondrocytes. In conclusion, we demonstrated that T4 enhances the
      cellular and molecular events of terminal differentiation and hypertrophy of
      chondrocytes in the three-dimensional cultures.

PMID- 12788087
TI  - Differentiation of rhesus embryonic stem cells to neural progenitors and neurons.
AB  - Embryonic stem (ES) cells are pluripotent cells capable of differentiating into
      cell lineages derived from all primary germ layers including neural cells. In
      this study we describe an efficient method for differentiating rhesus monkey ES
      cells to neural lineages and the subsequent isolation of an enriched population
      of Nestin and Musashi positive neural progenitor (NP) cells. Upon
      differentiation, these cells exhibit electrophysiological characteristics
      resembling cultured primary neurons. Embryoid bodies (EBs) were formed in ES
      growth medium supplemented with 50% MEDII. After 7 days in suspension culture,
      EBs were transferred to adherent culture and either differentiated in serum
      containing medium or expanded in serum free medium. Immunocytochemistry on
      differentiating cells derived from EBs revealed large networks of MAP-2 and NF200
      positive neurons. DAPI staining showed that the center of the MEDII-treated EBs
      was filled with rosettes. NPs isolated from adherent EB cultures expanded in
      serum free medium were passaged and maintained in an undifferentiated state by
      culture in serum free N2 with 50% MEDII and bFGF. Differentiating neurons derived
      from NPs fired action potentials in response to depolarizing current injection
      and expressed functional ionotropic receptors for the neurotransmitters glutamate
      and gamma-aminobutyric acid (GABA). NPs derived in this way could serve as models
      for cellular replacement therapy in primate models of neurodegenerative disease,
      a source of neural cells for toxicity and drug testing, and as a model of the
      developing primate nervous system.

PMID- 12788088
TI  - Cloning, sequencing, and characterization of the murine nm23-M5 gene during mouse
      spermatogenesis and spermiogenesis.
AB  - Nucleoside diphosphate kinases (NDPKs) are conserved throughout evolution and
      have been shown to be involved in various biological phenomena. By functional
      screening in yeast, we identified a new member of the NDPK family, nm23-M5, which
      encodes a 211-amino acid protein with 86% identity to the human homolog Nm23-H5.
      Northern blot analysis revealed that nm23-M5 encodes two transcripts of 0.8 and
      0.7kb, which are highly and specifically expressed in adult testis. Reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis showed that nm23-M5
      transcripts first appear in pachytene spermatocytes and increase in abundance in
      subsequent stages. However, a low level of nm23-M5 mRNA was detected by RT-PCR in
      other tissues, such as ovary, brain, heart, and kidney. In situ hybridization
      studies showed that testicular nm23-M5 transcripts are localized in stage 12 to
      stage 16 spermatids in the neighboring lumen of seminiferous tubules. This
      distribution contrasts with that of Nm23-H5 transcripts, which are specifically
      found in spermatogonia and early spermatocytes. The heterologous expression of
      nm23-M5 in yeast cells confers protection from cell death induced by Bax, which
      is due to the generation of reactive oxygen species. Furthermore, overexpression
      of nm23-M5 in fibroblasts altered the cellular levels of several antioxidant
      enzymes, particularly glutathione peroxidase 5. Thus, we believe that the murine
      nm23-M5 gene plays an important role in late spermiogenesis by elevating the
      ability of late-stage spermatids to eliminate reactive oxygen species.

PMID- 12788089
TI  - Stable expression of human melanocortin 3 receptor fused to EGFP in the HEK293
      cells.
AB  - Among the melanocortins alpha-MSH is known to be involved in feeding behavior.
      These hormones mediate their effects through G protein-coupled receptors by
      stimulating adenylate cyclase. In this study, we have developed an in vitro
      expression model for human melanocortin 3 receptor (hMC3R) tagged at its C
      terminus with EGFP. The corresponding chimeric cDNA was stably expressed in
      HEK293 cells. The selected clones expressing the hMC3R-EGFP exhibited cell
      surface fluorescence and responded to NDP-MSH stimulation by producing cAMP in a
      dose-dependent manner (EC(50): 0.3 nM). Binding studies revealed a single class
      of binding sites with a K(D) of 2.24 nM. Moreover, Agouti-related protein was
      also demonstrated to be an antagonist of the hMC3R-EGFP. Thus, the hMC3R tagged
      with EGFP stably expressed in HEK293 cells, exhibiting the same characteristics
      than the wild-type hMC3R, is the only model of expression of this receptor
      allowing its direct localization inside living cells.

PMID- 12788090
TI  - DNA hybridization assays using metal-enhanced fluorescence.
AB  - We describe a new approach to DNA hybridization assays using metal-enhanced
      fluorescence. Thiolated oligonucleotides were bound to silver particles on a
      glass substrate. Addition of a complementary fluorescein-labeled oligonucleotide
      resulted in a dramatic time-dependent 12-fold increase in fluorescence intensity
      during hybridization. Proximity to silver particles resulted in a decreased
      fluorescence lifetime. This effect is thought to be the result of enhanced
      fluorescence from fluorescein near metallic silver particles. Hybridization could
      thus be measured from the decay kinetics of the emission, which can be measured
      independently from the emission intensity. These results suggest the use of
      silver particles as a general approach to measure DNA hybridization as a method
      to increase the sensitivity of DNA detection.

PMID- 12788091
TI  - Incorporation of adult organ-derived endothelial cells into tumor blood vessel.
AB  - In this study, we attempted to assess the incorporable potential of vascular
      endothelial cells derived from adult organ blood vessels into tumor blood
      vessels. Two kinds of adult organ-derived vascular endothelial cells, human aorta
      endothelial cells (HAEC) and umbilical vein endothelial cells (HUVEC), were
      administered into murine tumors inoculated to SCID mice. Many human blood vessel
      networks were visualized in the murine tumors. These cells in solid tumor not
      only survived and proliferated, but also incorporated into tumor endothelium.
      These results suggest that adult organ-derived vascular endothelial cells possess
      the potential to form the neovascular network in various tissues such as vascular
      endothelial progenitor-like cells in vivo. We propose that these cells can be
      regarded as a congenic (autologous) vector for vascular regeneration cell therapy
      and tumor vascular targeting gene therapy.

PMID- 12788092
TI  - An investigation of phosphopeptide binding to SH2 domain.
AB  - A comparative molecular field analysis (CoMFA) was carried out to investigate
      quantitative structure-activity relationships for SH2-binding phosphopeptides.
      Two alignment rules were applied in our CoMFA model. The phosphopeptide backbone
      atoms were used for superposition in alignment I and the backbone atoms of
      peptide-binding residues of SH2-phosphopeptide complexes were used in alignment
      II to consider the position of phosphopeptides in SH2-binding sites. The higher
      correlation and predictivity in alignment II (r(2) value of 0.961 and cross
      validated r(2) value of 0.682) suggest that the consideration of peptide-binding
      position at the binding sites gives rise to better results when the ligand
      receptor complex structure is considered. In addition, CoMFA contour and
      electrostatic maps were well accorded with the experimental results in which the
      replacement of N-terminal residues with an acetyl group reduced the binding
      affinity. Therefore, the modification of molecular size and charge of
      phosphopeptides can be carried out based on these contour maps in order to
      increase binding affinities.

PMID- 12788093
TI  - A novel TBP-interacting zinc finger protein represses transcription by inhibiting
      the recruitment of TFIIA and TFIIB.
AB  - We isolated a novel gene encoding a zinc finger protein from Xenopus laevis,
      designated NZFP that interacts with the TATA-binding protein (TBP). NZFP contains
      a highly conserved sequence designated finger associated box (FAX) and SUMO-1
      consensus-binding motifs at the N-terminal half and 10 C2H2 type zinc finger
      motifs at the C-terminal half, respectively. Deletion mutants of NZFP fused with
      the Gal4 DNA binding domain were used to determine the function of NZFP during
      gene transcription by transfecting them into a Xenopus kidney cell line. Both
      full-length NZFP and the FAX domain repressed transcription activity by 3-5-fold.
      Moreover, an in vitro pull-down assay showed that the C-terminal core domain of
      TBP makes direct contact with the N-terminal portion of NZFP. We also found
      through chromatin immunoprecipitation experiments that the interaction between
      NZFP and TBP inhibits binding of TFIIA and TFIIB. These data strongly suggest
      that the repression by NZFP occurs through its binding to both DNA and TBP and
      the resulting NZFP-TBP-promoter complex inhibits preinitiation complex assembly
      by preventing binding of TFIIA and TFIIB.

PMID- 12788094
TI  - Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr
      promoter.
AB  - The dihydrofolate reductase (dhfr) promoter contains cis-acting elements for Sp1
      and E2F. Here we examined the cooperative regulation of dhfr gene transcription
      by Sp1 and E2F in human osteosarcoma cells, U2OS. Trichostatin A, an inhibitor of
      histone deacetylases, markedly stimulated dhfr promoter activity, a response that
      was enhanced by the deletion of an E2F element. In contrast, deletion of the dhfr
      Sp1 binding sites completely abolished promoter stimulation by trichostatin A.
      Cotransfection assays showed that activation of dhfr transcription by expression
      of E2F1/DP1 requires the reiterated Sp1 elements, whereas activation by Sp1 was
      enhanced by the deletion of the E2F element. Expression of HDAC1 with Sp1
      suppressed promoter activity and suppression was not alleviated by coexpression
      of E2F1/DP1. These results suggest that HDAC1 acts through Sp1 to repress dhfr
      promoter activity, and that the E2F element modulates the activity of Sp1 at the
      dhfr promoter through a cis-acting mechanism.

PMID- 12788095
TI  - Central involvement of Rho family GTPases in TNF-alpha-mediated bovine pulmonary
      endothelial cell apoptosis.
AB  - In our recent studies, we defined a critical role for increased levels of myosin
      light chain (MLC) phosphorylation, a regulatory event in the interaction between
      actin and myosin in TNF-alpha-induced pulmonary endothelial cell actomyosin
      rearrangement and apoptosis. The Rho GTPase effector, Rho kinase is an important
      signaling effector governing levels of MLC phosphorylation which contributes to
      plasma membrane blebbing in several models of apoptosis. In this study, we
      directly assessed the role of Rho kinase in TNF-alpha-induced endothelial cell
      microfilament rearrangement and apoptosis. Inhibition of RhoA GTPase activity by
      the overexpression of dominant negative RhoA attenuates TNF-alpha-triggered
      stress fiber formation, consistent with Rho activation as a key event in TNF
      alpha-induced cytoskeletal rearrangement. Furthermore, pharmacologic inhibition
      of Rho kinase as well as dominant negative RhoA overexpression dramatically
      reduced TNF-alpha-induced bovine endothelial apoptosis reflected by nucleosomal
      fragmentation as well as caspase 7, 3, and 8 activation. These results indicate
      that Rho kinase-dependent cytoskeletal rearrangement is critical for early
      apoptotic events, possibly in the assembly of the death-inducing signaling
      complex leading to initiator and effector caspase activation, and suggest a novel
      role for Rho GTPases in endothelial cell apoptosis.

PMID- 12788096
TI  - Rapid transport of phospholipids across the plasma membrane of Leishmania
      infantum.
AB  - The internalization of fluorescent phospholipid analogs of phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and sphingomyelin
      (SM) in Leishmania infantum promastigotes was studied. We observed a rapid inward
      redistribution of NBD-PC, -PE, and -PS across the plasma membrane at 28 and 4
      degrees C. This internalization was shown to be independent of the endocytic
      activity of parasites. Rapid inward movement was coupled to an energy-dependent
      transporter because it was almost inhibited by depletion of cellular ATP and was
      blocked after pretreatment with N-ethylmaleimide (NEM). In contrast, NBD-SM
      traverses the plasma membrane by passive flip-flop. By comparing this pattern of
      phospholipid transbilayer movement with those known from other eukaryotic cells,
      candidate lipid transporters are discussed.

PMID- 12788097
TI  - Hemostatic effects of polymerized albumin particles bearing rGPIa/IIa in
      thrombocytopenic mice.
AB  - The recombinant fragment of the platelet membrane glycoprotein Ia/IIa (rGPIa/IIa)
      was conjugated to the polymerized albumin particles (polyAlb) with the average
      diameter of 180 nm. The intravenous administration of rGPIa/IIa-polyAlb to
      thrombocytopenic mice ([platelet] = 2.1+/-0.3 x 10(5) particles/ microL) with
      three doses of ca. 2.4 x 10(10), 7.2 x 10(10), and 2.4 x 10(11)particles/kg,
      respectively, significantly reduced their bleeding time to 426+/-71, 378+/-101,
      and 337+/-46 s, respectively, whereas that of the control groups (PBS) was 730+/
      198 s. The injection of rGPIa/IIa-polyAlb (2.4 x 10(11)particles/kg) was
      approximately equal to the effect of the injection of the mouse platelets at a
      dose of 2.0 x 10(10) particles/kg. It was confirmed that rGPIa/IIa-polyAlb had a
      recognition ability against collagen and could contribute to the hemostasis in
      the thrombocytopenic mice as a platelet substitute.

PMID- 12788098
TI  - Platelet-activating factor modulates gastric mucosal inflammatory responses to
      Helicobacter pylori lipopolysaccharide.
AB  - Platelet-activating factor (PAF) is a phospholipid messenger implicated in
      mediation of inflammatory events associated with the resolution of inflammation.
      We applied the animal model of Helicobacter pylori LPS-induced gastritis in
      conjunction with prophylactic and therapeutic administration of a specific PAF
      antagonist, BN52020, to investigate the role of PAF in gastric mucosal responses
      to H. pylori infection. Prophylactic BN52020 administration produced up to 73.6%
      reduction in the severity of the LPS-induced inflammatory changes, whereas up to
      38.4% increase in the severity of mucosal involvement occurred with BN52020
      administered therapeutically. The prophylactic effects of BN52020 were
      accompanied by a drop in apoptosis and the expression of TNF-alpha and NOS-2,
      while BN52020 administered therapeutically caused a marked upregulation in
      apoptosis, TNF-alpha, and NOS-2. The untoward therapeutic effects of BN52020,
      moreover, were potentiated further in the presence of COX-2 inhibitor, whereas
      NOS-2 inhibitor caused a reduction in the extent of inflammatory changes. Our
      findings point to PAF as a key mediator of gastric mucosal inflammatory responses
      to H. pylori and suggest its modulatory role in the expression of COX-2 derived
      anti-inflammatory prostaglandins that are involved in controlling the extent of
      NOS-2 induction.

PMID- 12788099
TI  - Modulation of YY1 activity by SAP30.
AB  - Yin Yang 1 (YY1) is a highly conserved and multifunctional transcription factor.
      The diverse activities of YY1 are regulated and sometimes modified by interaction
      with various other proteins. By using a yeast two-hybrid screening system, SAP30
      was identified as a protein that associates with YY1 and it is able to enhance
      YY1-mediated repression in a dose-dependent manner. SAP30 is a 30kDa nuclear
      protein and is a component of the human histone deacetylase complex. In this
      study, the interaction of SAP30 and YY1 was confirmed both by in vitro and in
      vivo assays. The interaction domains between YY1 and SAP30 were mapped to the C
      terminal segment of YY1 (295-414) and the C-terminal 91 amino acid region of
      SAP30. The observation that YY1, SAP30, and HDAC1 form a complex in vivo provides
      evidence that YY1 also recruits HDAC1 indirectly via its binding to SAP30. These
      results describe a novel mechanism for YY1-mediated repression.

PMID- 12788100
TI  - Differentiation-dependent regulation of skeletal myogenesis by neuregulin-1.
AB  - Neuregulins comprise a group of growth factor proteins that regulate the
      differentiation of skeletal muscle. Here, we report that neuregulins are
      regulators of myogenic differentiation and stimulate mitogenesis in L6 skeletal
      myoblasts. The mitogenic response to neuregulin-1 was differentiation-dependent
      and observed only in aligned, differentiating cells. Treatment of these cells
      with neuregulin-1 increased [3H]thymidine incorporation and cell proliferation by
      2- to 5-fold, while a minimal increase was seen in proliferating myoblasts.
      Neuregulin-1 did not induce DNA synthesis in fused, multinucleated myotubes. The
      increased DNA synthesis correlated with downregulation of myogenin and inhibition
      of myoblast fusion and myotube formation. These data suggest that neuregulins may
      regulate skeletal myogenesis in vivo and that this regulation is dependent on the
      state of differentiation of the myocytes.

PMID- 12788101
TI  - Brain microvessel endothelin type A receptors are coupled to ceramide production.
AB  - Treatment of brain microvessels with endothelin-1 evoked an early decrease in the
      sphingomyelin levels concomitantly with an increase in those of ceramides. These
      responses were time- and concentration-dependent. Evidence also shows that
      endothelin type A receptors are involved. This is the first report on the
      involvement of an agonist in the regulation of the ceramide signal transduction
      system on blood-brain barrier and shows a new pathway likely involved in the
      regulation of the cerebral microvascular functioning.

PMID- 12788102
TI  - Disturbed secretion of mutant adiponectin associated with the metabolic syndrome.
AB  - Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and
      complement C1q-like globular domains, and circulates in human plasma in a
      multimeric form. The protein exhibits anti-diabetic and anti-atherogenic
      activities. However, adiponectin plasma concentrations are low in obese subjects,
      and hypoadiponectinemia is associated with the metabolic syndrome, which is a
      cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and
      dyslipidemia. We have recently reported a missense mutation in the adiponectin
      gene, in which isoleucine at position 164 in the globular domain is substituted
      with threonine (I164T). Subjects with this mutation showed markedly low level of
      plasma adiponectin and clinical features of the metabolic syndrome. Here, we
      examined the molecular characteristics of the mutant protein associated with a
      genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant
      protein showed an oligomerization state similar to the wild-type as determined by
      gel filtration chromatography and, (2) the mutant protein exhibited normal
      insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion
      of the mutant protein from adipose tissues. Our results suggest that I164T
      mutation is associated with hypoadiponectinemia through disturbed secretion into
      plasma, which may contribute to the development of the metabolic syndrome.

PMID- 12788103
TI  - Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T.
AB  - Arylsulfatase A (ARSA) is a lysosomal enzyme implicated in most cases of
      metachromatic leukodystrophy (MLD). The quaternary structure of ARSA is pH
      dependent: at neutral pH, ARSA is a homodimeric protein; at lysosomal (acidic)
      pH, ARSA is homo-octameric. This dimer-octamer transition seems to be of major
      importance for the stability of the enzyme in the lysosomal milieu. Sedimentation
      analysis was used to study the oligomerization capacity of C300F and P425T
      substituted ARSA, two MLD-associated forms of the enzyme displaying reduced
      lysosomal half-lives. P425T-ARSA displays a modest reduction in its
      octamerization capacity. In contrast, the C300F mutation strongly interferes with
      the octamerization process of ARSA but not with its dimerization capacity.
      Interestingly, a major fraction of dimeric ARSA-C300F is composed of covalently
      linked ARSA molecules, through a thiol-cleavable bond that probably involves
      Cys414 residues from each monomer. Our data support the notion that the reduced
      lysosomal half-life of some mutated forms of ARSA is related to deficient
      octamerization.

PMID- 12788104
TI  - SNAP-25 inhibits L-type Ca2+ channels in feline esophagus smooth muscle cells.
AB  - We recently reported that non-secretory gastrointestinal smooth muscle cells also
      possessed SNARE proteins, of which SNAP-25 regulated Ca(2+)-activated (K(Ca)) and
      delayed rectifier K(+) channels (K(V)). Voltage-gated, long lasting (L-type)
      calcium channels (L(Ca)) play an important role in excitation-contraction
      coupling of smooth muscle. Here, we show that SNAP-25 could also directly inhibit
      the L-type Ca(2+) channels in feline esophageal smooth muscle cells at the SNARE
      complex binding synprint site. SNARE proteins could therefore regulate additional
      cell actions other than membrane fusion and secretion, in particular, coordinated
      muscle membrane excitability and contraction, through their actions on membrane
      Ca(2+) and K(+) channels.

PMID- 12788105
TI  - Tocotrienols induce IKBKAP expression: a possible therapy for familial
      dysautonomia.
AB  - Familial dysautonomia (FD), a neurodegenerative genetic disorder primarily
      affecting individuals of Ashkenazi Jewish descent, is caused by mutations in the
      IKBKAP gene which encodes the IkappaB kinase complex-associated protein (IKAP).
      The more common or major mutation causes aberrant splicing, resulting in a
      truncated form of IKAP. Tissues from individuals homozygous for the major
      mutation contain both mutant and wild-type IKAP transcripts. The apparent leaky
      nature of this mutation prompted a search for agents capable of elevating the
      level of expression of the wild-type IKAP transcript. We report the ability of
      tocotrienols, members of the vitamin E family, to increase transcription of IKAP
      mRNA in FD-derived cells, with corresponding increases in the correctly spliced
      transcript and normal protein. These findings suggest that in vivo
      supplementation with tocotrienols may elevate IKBKAP gene expression and in turn
      increase the amount of functional IKAP protein produced in FD patients.

PMID- 12788106
TI  - Seven GC-rich microbial genomes adopt similar codon usage patterns regardless of
      their phylogenetic lineages.
AB  - Seven GC-rich (group I) and three AT-rich (group II) microbial genomes are
      analyzed in this paper. The seven microbes in group I belong to different
      phylogenetic lineages, even different domains of life. The common feature is that
      they are highly GC-rich organisms, with more than 60% genomic GC content. Group
      II includes three bacteria, which belong to the same subdivision as Pseudomonas
      aeruginosa in group I. The genomic GC content of the three bacteria is in the
      range of 26-50%. It is shown that although the phylogenetic lineages of the
      organisms in group I are remote, the common feature of highly genomic GC content
      forces them to adopt similar codon usage patterns, which constitutes the basis of
      an algorithm using a set of universal parameters to recognize known genes in the
      seven genomes. The common codon usage pattern of function known genes in the
      seven genomes is GGS type, where G, G, and S are the bases of G, non-G, and G/C,
      respectively. On the contrary, although the phylogenetic lineages of the three
      bacteria in group II are quite close, the codon usage patterns of function known
      genes in these genomes are obviously distinct. There are no universal parameters
      to identify known genes in the three genomes in group II. It can be deduced that
      the genomic GC content is more important than phylogenetic lineage in gene
      recognition programs. We hope that the work might be useful for understanding the
      common characteristics in the organization of microbial genomes.

PMID- 12788107
TI  - Multiple forms of medicinal leech destabilase-lysozyme.
AB  - Earlier, three genes Ds1, Ds2, and Ds3 encoding corresponding destabilase
      lysozyme isoforms were identified. However only one form of the enzyme encoded by
      Ds3 gene coincided with the protein CNBr fragments [Mol. Gen. Genet. 253 (1996)
      20]. In this work we found by ESI-TOF mass spectrometry that the enzyme
      preparation consists of at least three forms with molecular masses of 12677.6,
      12839.7, and 12938.2Da, each of which contains seven disulfide bridges. Only one
      mass (12839.7Da) fits to the calculated mass for the protein encoded by Ds3 gene.
      Further analysis of the CNBr fragments of the enzyme showed the heterogeneity of
      large 5.5 kDa peptide at positions 64 (threonine or arginine) and 67 (histidine
      or arginine) in the wild-type amino acid sequence. One CNBr peptide, with Arg and
      His at positions 64 and 67, respectively, correlates in the molecular mass with
      the protein encoded by Ds3. In addition, we have found a new acid form of
      destabilase-lysozyme, P-Ac, which differs from all known destabilase-lysozyme
      structures by its N-terminal amino acid sequence.

PMID- 12788108
TI  - Promoting communication with older adults: protocols for resolving interpersonal
      conflicts and for enhancing interactions with doctors.
AB  - In this paper, we review the importance of effective communication in older
      adulthood, and ideas for promoting it. We focus on theoretical and applied work
      in two communicative encounters that have particular relevance for older adult
      health, i.e., interpersonal conflict and visits with a healthcare provider.
      Little applied work has aimed to adapt training protocols for older adults in
      these two areas. We will present training protocols we have developed in
      constructive conflict resolution for older adults, and on enhancing doctor
      patient communication. We present these protocols to stimulate ideas on the part
      of the reader on how to further develop and refine training efforts for older
      adults in effective communication.

PMID- 12788109
TI  - The role of childhood sexual abuse sequelae in the sexual revictimization of
      women: an empirical review and theoretical reformulation.
AB  - There is now widespread empirical evidence that child sexual abuse (CSA)
      survivors are at greater risk for sexual revictimization in adulthood, but less
      is known of the mechanisms underlying this relationship. Despite the lack of a
      conceptual framework to guide research, there has been a recent influx of studies
      examining explanatory variables, with most focusing on the psychological sequelae
      of CSA: alcohol and drug use, sexual behavior, dissociation, posttraumatic
      symptomatology, poor risk recognition, and interpersonal difficulties. With the
      exception of sexual behavior, the studies reviewed here provide limited or mixed
      support for the role of intrapersonal factors in revictimization. Future research
      may benefit from a focus on the function of psychological distress that is
      expressed as psychological vulnerability, as opposed to individual forms of
      psychopathology or maladaptive behavior. An ecological framework may be useful as
      a guide to future investigations, as this model focuses on factors outside of the
      victim, including childhood factors such as family environment, contextual
      factors including the behavior of the perpetrator, and societal and cultural
      factors that impact revictimization. Future investigations should focus on the
      interaction between victim vulnerability and perpetrator behavior. Implications
      for prevention programming, clinical intervention, and future research are
      discussed.

PMID- 12788110
TI  - Towards a better understanding of gambling treatment failure: implications of
      translational research.
AB  - Despite a recent proliferation of gambling treatment protocols and studies
      examining the success of these protocols, there exists an absence of attention to
      mechanisms of change and the individual characteristics that predict treatment
      outcome. A better understanding of the characteristics that place particular
      individuals at-risk for treatment failure will be vital for developing new
      treatments as well as modifying existing treatments. Furthermore, the development
      of tools to identify those at risk for treatment failure, prior to treatment
      initiation, will allow for the tailoring of protocols to suit individual needs
      and vulnerabilities. In the current paper, we review the state of gambling
      treatment and suggest a framework for better understanding and ultimately
      reducing gambling treatment failure.

PMID- 12788111
TI  - Posttraumatic disorders following injury: an empirical and methodological review.
AB  - Although there has been a marked increase in research on psychological disorders
      following physical injury in recent years, there are many discrepancies between
      the reported findings. This paper reviews the prevalence outcomes of recent
      studies of the mental health sequelae of physical injury with a focus on
      posttraumatic stress disorder (PTSD), acute stress disorder (ASD), and
      depression. The review critically outlines some of the methodological factors
      that may have contributed to these discrepancies. The phenomenological overlap
      between organic and psychogenic symptoms, the use of narcotic analgesia, the role
      of brain injury, the timing and content of assessments, and litigation are
      discussed in terms of their potential to confound findings with this population.
      Recommendations are proposed to clarify methodological approaches in this area.
      It is suggested that a clearer understanding of the psychological effects of
      physical injury will require the widespread adoption of more rigorous,
      standardized and transparent methodological procedures.

PMID- 12788113
TI  - Factors related to severe uveitis at diagnosis in children with juvenile
      idiopathic arthritis in a screening program.
AB  - PURPOSE: To identify factors associated with severe uveitis at diagnosis of eye
      disease in children with juvenile idiopathic arthritis (JIA) who were observed in
      a screening program, and to identify temporal changes in findings associated with
      screening during the period 1986 to 2000. DESIGN: Case control study. METHOD:
      Uveitis was defined as being severe at diagnosis if there were associated
      synechiae, cataracts, or retinal edema. Clinical factors for all patients
      undergoing screening for JIA-associated uveitis from 1986 to 2000 at one
      institution were studied retrospectively. Children with severe uveitis at
      diagnosis (cases) were compared with those with mild uveitis at diagnosis and
      those who never developed uveitis during follow-up in the screening program
      (controls). RESULTS: Severe uveitis was present at diagnosis in 22 (5.4%) of 409
      patients. Male patients were more likely to have severe uveitis at diagnosis
      (odds ratio [OR] 3.7 [95% confidence interval 1.3 to 10.7], P =.014). A longer
      interval from the onset of arthritis symptoms to the diagnosis of uveitis was
      associated with a reduced risk of severe uveitis at diagnosis (OR 0.95 [0.91 to
      1.0], P =.044). There was no difference in the frequency of severe uveitis at
      diagnosis between two screening periods: 1986 to 1993 (before American screening
      guidelines were published) and 1994 to 2000. CONCLUSIONS: Male children are more
      likely than female children to have severe uveitis at diagnosis. The proportion
      of children with severe uveitis at diagnosis has not changed since current
      screening guidelines have been widely publicized, suggesting the need for
      refinements in screening procedures to target high-risk children with increased
      surveillance.

PMID- 12788112
TI  - The relation between depression and anxiety: an evaluation of the tripartite,
      approach-withdrawal and valence-arousal models.
AB  - Epidemiological studies have consistently reported that depressive and anxiety
      disorders co-occur frequently. This paper reviews the evidence for three models
      that have been proposed to explain the relation between these two conditions-the
      tripartite, the approach-withdrawal, and valence-arousal models. Specifically, we
      focus on predictions that the three models generate for cross-sectional studies,
      prospective and family/twin studies of personality, and EEG studies. In sum, no
      model was strongly supported across all types of studies, though specific aspects
      of each model were. Because of the heterogeneity of depression and anxiety
      disorders, a model with 2-4 factors or dimensions may not be sufficient to
      explain the relation between the two conditions.

PMID- 12788114
TI  - Laser flare photometry and complications of chronic uveitis in children.
AB  - PURPOSE: To investigate possible relationships between laser flare photometry
      values, complications of uveitis, and outcomes in children with chronic uveitis.
      DESIGN: Retrospective chart review. METHOD: We evaluated patients with active,
      noninfectious anterior, intermediate, or panuveitis who were 16 years of age or
      younger and who had laser flare photometry at one of two academic institutions.
      Complications enumerated at baseline and during follow-up were compared with
      laser flare photometry values and to anterior chamber cell counts. RESULTS: At
      least one laser flare photometry value ("flare"), defined as baseline
      measurement, was available for 59 patients (41 girls, 18 boys; mean age, 10.3 +/-
      3.5 years); 38 of these patients had at least one additional measurement during
      follow-up (median 11 months). Complications of uveitis were present in 35
      patients (59%) at baseline. There was a positive association between increased
      laser flare photometry values and complications at baseline (any complication [P
      =.007], posterior synechiae [P =.003]). The development of complications during
      follow-up was associated with the presence of complications at baseline (P
      =.018). A subgroup of patients with low flare at baseline had no complications
      during follow-up regardless of treatment given. CONCLUSIONS: There is a positive
      relationship between laser flare photometry values and the prevalence of
      complications of uveitis in children. Laser flare photometry provides a novel way
      to monitor children with uveitis. Future study will be needed to determine
      whether values have prognostic importance and whether a treatment strategy that
      minimizes flare results in fewer uveitic complications.

PMID- 12788115
TI  - Surgical management of cataracts in children with juvenile rheumatoid arthritis
      associated uveitis.
AB  - PURPOSE: To evaluate outcomes of cataract surgery with posterior chamber
      intraocular lens (IOL) implantation with or without trabeculectomy in children
      with juvenile rheumatoid arthritis (JRA)-associated uveitis. DESIGN:
      Interventional case series. METHOD: Retrospective chart review of five patients
      aged 12 years or younger with JRA-associated uveitis who underwent cataract
      surgery with posterior chamber IOL with or without trabeculectomy at the
      Cleveland Clinic Foundation from December 1995 to October 2001. RESULTS: Four
      female patients and one male patient ranging from age 7 to 12 years were
      identified. One patient had bilateral involvement; six eyes were included in the
      study. Three eyes underwent cataract extraction with posterior chamber IOL, and
      three underwent combined cataract surgery with posterior chamber IOL and
      trabeculectomy. Median age at surgery was 8.5 years, with a median follow-up of
      43.5 months. Four of five children (five eyes) were on systemic methotrexate
      immunosuppressive therapy for a median length of 1.25 years before surgery. Two
      of five patients (three eyes) were also on additional systemic immunosuppressive
      or anti-inflammatory treatments. All eyes received frequent topical
      corticosteroid therapy for a median of 2 weeks preoperatively and 8.5 weeks
      postoperatively. A final postoperative Snellen visual acuity of 20/40 or better
      was achieved in all children. A median final visual acuity improvement of 7
      Snellen lines was observed after cataract surgery. CONCLUSIONS: With adequate
      long-term preoperative and postoperative control of intraocular inflammation with
      systemic immunosuppressive therapy in addition to intensive topical
      corticosteroid treatment, children with JRA-associated uveitis can demonstrate
      favorable surgical outcomes after cataract surgery with posterior chamber IOL.

PMID- 12788116
TI  - Ophthalmic outcomes after prenatal and postnatal treatment of congenital
      toxoplasmosis.
AB  - PURPOSE: To describe the ophthalmologic outcomes of cases of congenital
      toxoplasmosis treated prenatally and postnatally. DESIGN: Observational case
      series. METHOD: Follow-up ophthalmologic examinations of 18 children born to
      mothers who were infected before 25 weeks gestation were performed concurrently
      by two ophthalmologists. The infection in these children was first suspected when
      their mothers seroconverted during gestation. Toxoplasmic infection of the fetus
      was diagnosed by fetal blood or amniotic fluid analysis. Mothers were treated by
      a regimen of alternating pyrimethamine-sulfonamides and spiramycin during
      gestation. Pyrimethamine-sulfonamides treatment was continued from birth to 1
      year of age. RESULTS: The median age of the children was 4.5 years (range 1-11),
      when the follow-up ophthalmologic examinations were performed. Visual acuity was
      decreased in only one child, who had extensive bilateral macular and peripheral
      lesions. A posterior pole scar was noted in four eyes (four children) for whom
      visual acuity remained normal. Peripheral lesions were observed in nine eyes
      (five children). Both eyes were normal in 11 of 18 (61%) of the children.
      CONCLUSIONS: In these children at a high risk for congenital toxoplasmic
      retinochoroiditis, a favorable visual outcome was observed in all but one case.

PMID- 12788117
TI  - Assessment of visual function after corneal transplantation: the quality of life
      and psychometric assessment after corneal transplantation (Q-PACT) study.
AB  - PURPOSE: Many patients with successful corneal grafts have poor vision
      postoperatively. This study evaluates changes in vision-related quality of life
      after penetrating keratoplasty (PK). DESIGN: Multicenter prospective cohort
      study. METHOD: Penetrating keratoplasty candidates from the university-affiliated
      ophthalmology clinics of four participating centers were enrolled and followed up
      prospectively. We used the PK-VFQ, a modified version of the Visual Function
      Index-14, combined with clinical examinations before and at 6 and 12 months after
      PK. We used multivariate linear regression models to examine predictors of change
      in PK-VFQ scores. RESULTS: We studied 74 grafts in 71 eyes of 67 patients aged 23
      to 91 (mean, 61) years who were followed up for at least 6 months. Indications
      for surgery included bullous keratopathy (27%), scarring (16%), keratoconus
      (16%), dystrophies (16%), and regrafts (15%). Median preoperative visual acuity
      was 20/200 in the graft candidate and 20/30 in the best eye. Median best
      corrected postoperative visual acuity in the operated eyes was 20/60 at 6 months.
      PK-VFQ scores improved at 6 months in 79% by an average of 13.0 points (range, 
      16.7 to 67.5). Improvement in PK-VFQ scores was associated with younger age (P
      =.04), poorer preoperative visual acuity in the best eye (P =.001), and
      postoperative contact lens use (P =.04) but not with postoperative acuity in the
      grafted eye (P =.49). Postoperatively, 80% of patients were moderately to very
      satisfied with their vision, and 97% of patients stated they would have the
      surgery again. CONCLUSIONS: Improvement in visual function is inversely
      associated with visual acuity in the better-seeing eye but does not correlate
      with the postoperative acuity in the grafted eye. Although most keratoplasties
      are done unilaterally in the setting of good visual acuity in the contralateral
      eye, for the majority of patients visual function improves after PK.

PMID- 12788118
TI  - What is the risk of developing pigmentary glaucoma from pigment dispersion
      syndrome?
AB  - PURPOSE: To determine the probability of converting from pigment dispersion
      syndrome to pigmentary glaucoma. DESIGN: Retrospective community-based study of
      all newly diagnosed cases of pigment dispersion syndrome or pigmentary glaucoma.
      METHOD: Subjects were patients newly diagnosed with pigment dispersion syndrome
      or pigmentary glaucoma from 1976 to 1999 in Olmsted County, Minnesota. Criteria
      for pigment dispersion syndrome were two of three signs: midperipheral, radial
      iris transillumination defects; Krukenberg spindle; heavy trabecular meshwork
      pigmentation. Criteria for pigmentary glaucoma were pigment dispersion syndrome
      and two of three findings: intraocular pressure (IOP) greater than 21 mm, optic
      nerve damage, or visual field loss. Kaplan-Meier survival curves were used to
      determine the probability of conversion to pigmentary glaucoma. RESULTS: A total
      of 113 patients were newly diagnosed with pigment dispersion syndrome over the 24
      year period. Of these, 9 persons developed pigmentary glaucoma or elevated IOP
      requiring therapy. The probability of converting to pigmentary glaucoma was 10%
      at 5 years and 15% at 15 years. An additional 23 patients were found to have
      pigmentary glaucoma at their initial examination. The mean age at diagnosis of
      pigmentary glaucoma was 42 +/- 12 years; 78% of patients were male, whereas 58%
      of patients with pigmentary dispersion syndrome glaucoma were male. The most
      significant risk factor for conversion to pigmentary glaucoma was an IOP greater
      than 21 mm Hg at initial examination, whereas age, refractive error, and family
      history of glaucoma were not correlated with conversion. CONCLUSIONS: The risk of
      developing pigmentary glaucoma from pigment dispersion syndrome was 10% at 5
      years and 15% at 15 years. Young, myopic men were most likely to have pigmentary
      glaucoma. An IOP greater than 21 mm Hg at initial examination was associated with
      an increased risk of conversion.

PMID- 12788119
TI  - Conjunctival melanoma: is it increasing in the United States?
AB  - PURPOSE: While the incidence of cutaneous melanoma has been found to have
      increased over time, the evidence for conjunctival melanoma is not as clear. We
      applied a large cancer registry database to determine whether any changes had
      occurred in the incidence of conjunctival melanoma. DESIGN: Descriptive
      epidemiologic analysis. METHOD: Using population-based registry data from the
      Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer
      Institute (NCI), we identified 206 newly diagnosed patients with conjunctival
      melanoma from 1973 to 1999. For analysis purposes, we calculated age-adjusted
      incidence rates and described temporal changes, using joinpoint regression model.
      RESULTS: Overall estimated biannual percent change (EBAPC) was 5.5 (95%
      confidence interval [CI] = 2.3, 8.8; P <.001). The significant elevated trend was
      observed for white men (EBAPC = 11.2; 95% CI = 6.3, 16.3; P <.001) but not for
      white women (EBAPC = 0.3; 95% CI = -4.1, 4.9; P >.05). In white men, the
      incidence rate increased 295% within the 27 years. Our analysis also showed a
      significant upward trend in the age group aged 60 years or more (EBAPC = 7.6; 95%
      CI = 3.9, 11.3; P <.001). Incidence tended to rise in the group aged 40 to 59
      years, but it was not statistically significant (EBAPC = 4.4; 95% CI = -2.3,
      11.6; P =.1536). CONCLUSIONS: Substantial temporal changes in the incidence of
      conjunctival melanoma have occurred in the United States in recent years. The
      changing incidence patterns coincide with those seen in cutaneous melanoma,
      suggesting a possible link to a sunlight-related etiology.

PMID- 12788120
TI  - Surgical technique for control of postkeratoplasty myopia, astigmatism, and
      anisometropia.
AB  - PURPOSE: We previously demonstrated that selective suture removal reduces
      keratoplasty astigmatism; however, a myopic shift was induced with the increasing
      number of interrupted sutures removed. This study is an attempt to determine the
      effects of a modified surgical technique on postkeratoplasty myopia, astigmatism,
      and anisometropia. DESIGN: A cohort study compared with historical controls.
      METHOD: Optical penetrating keratoplasties were performed on 92 eyes of 84
      patients. The study group consisted of 92 consecutive penetrating keratoplasties
      performed using 12 interrupted 10-0 nylon sutures and a tight 12-bite continuous
      suture and an average K reading of 46.00 diopters for eyes undergoing combined
      and intraocular lens exchange procedures. All patients had refraction,
      keratometry, and videokeratoscopy postoperatively starting at 6 weeks and at the
      completion of selective suture removal. RESULTS: Before suture removal, the
      average spherical equivalent was -0.160 +/- 3.59 diopters; it was -1.58 +/- 3.66
      diopters at the completion of suture removal at 1 year and -1.44 +/- 3.72 at the
      last follow-up visit, averaging 20.7 months. Final refractive, keratometric, and
      videokeratoscopy astigmatism was 2.81 +/- 1.82, 4.19 +/- 2.94, and 3.58 +/- 2.03
      diopters, respectively. Anisometropia, using the spherical equivalent of the
      operated and fellow eyes, was 2.49 +/- 2.25 diopters at completion of the study.
      A best-corrected visual acuity of 20/50 or better was achieved in 59% of
      patients. CONCLUSIONS: Low myopic spherical equivalent and anisometropia were
      achieved using a K reading of 46 diopters for calculation of intraocular lens
      power. The use of tighter continuous sutures and selective removal of fewer
      interrupted sutures only served to increase final astigmatism, with no
      significant effect on the final spherical equivalent.

PMID- 12788121
TI  - Is reading disability likely to interfere with glaucoma screening of adults using
      frequency-doubling technology perimetry?
AB  - PURPOSE: The present study is a preliminary investigation of whether frequency
      doubling technology perimetry (FDT) performance deficits exist in adults with
      reading disability (RD) and could thereby interfere with screening assessments
      for glaucoma. DESIGN: Cross-sectional. METHOD: The study population was composed
      of 46 college students. Twenty-four of the participants were identified as having
      a RD, and 22 served as controls. All participants underwent assessments of
      reading, IQ, FDT, Humphrey Visual Fields (HVF), and an ophthalmologic
      examination. RESULTS: No differences between the RD and control groups were found
      in age, education, IQ, far visual acuity, HVF, or FDT performance, regardless of
      how FDT was evaluated (P's >.05). CONCLUSIONS: Preliminary results indicate that
      FDT performance deficits, which have previously been demonstrated in children
      with RD, are either small in magnitude or do not exist in adults. Thus, it is
      unlikely that RD will interfere with assessment for glaucoma using FDT perimetry.

PMID- 12788122
TI  - The Ahmed drainage implant in the treatment of pediatric glaucoma.
AB  - PURPOSE: To report the safety and efficacy of Ahmed Glaucoma Valve (New World
      Medical, Inc., Rancho Cucamonga, California, USA) implantation for the management
      of pediatric glaucoma in the early and intermediate follow-up period. DESIGN:
      Consecutive interventional case series. METHOD: A retrospective chart review was
      conducted on 60 eyes (44 patients, age range at surgery 1.5 months to 16 years,
      average 6 +/- 4.9 years), with pediatric glaucoma that underwent Ahmed Glaucoma
      Valve implantation for medically uncontrolled intraocular pressure (IOP) between
      the years 1995 and 2000. Outcome measures were control of IOP below 21 mm Hg, the
      need for antiglaucoma medications after surgery, and loss of 2 or more lines of
      Snellen acuity. Complications were monitored. RESULTS: The postoperative follow
      up period for each eye averaged 24.3 +/- 16 months (range, 3 to 60 months). At
      last follow-up, IOP was controlled in 44 eyes (73%), 11 of which did not need
      antiglaucoma therapy. Kaplan-Meier life-table analysis showed probability of
      success with or without medications of 93% (95% confidence interval [CI], 86%
      100%), 86% (95% CI, 77%-96%), 71% (95% CI, 59%-87%), and 45% (95% CI, 28%-80%)
      after 12, 24, 36, and 48 months of follow-up. Average IOP decreased from 32.8 +/-
      6.2 before surgery to 16.6 +/- 8.0 postoperatively (P <.0001). The average number
      of medications used decreased from 4.4 +/- 1.97 to 2.0 +/- 2.0 (P <.0001). Kaplan
      Meier survival analysis did not reveal any difference in survival profiles
      related to specific diagnosis of glaucoma, age (above or below 18 months), or
      prior surgery. Complications occurred in 30 eyes (50%). Although most resolved or
      were treated successfully, four patients had severe visual loss during the follow
      up. Uveitis was a significant risk factor for tube exposure (Fisher exact test, P
      =.006). CONCLUSIONS: Ahmed Glaucoma Valve implantation is an effective treatment
      for pediatric glaucoma, although patients frequently require antiglaucoma
      medications. However, a high rate of potentially sight-threatening postoperative
      complications warrants ongoing close follow-up.

PMID- 12788123
TI  - Pseudoexfoliation in a rural population of southern India: the Aravind
      Comprehensive Eye Survey.
AB  - PURPOSE: To determine the prevalence and risk factors for pseudoexfoliation in a
      rural population of southern India. DESIGN: A population-based cross-sectional
      study of pseudoexfoliation with and without glaucoma in rural southern India.
      METHOD: A total of 5,150 subjects aged 40 years and older from 50 clusters
      representative of three southern districts of Tamil Nadu in southern India.
      RESULTS: All participants had a comprehensive eye examination at the base
      hospital, including visual acuity using logarithm of minimal angle of resolution
      (logMAR) illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy,
      applanation tonometry, dilated fundus examinations, and automated central 24-2
      full-threshold perimetry. Pseudoexfoliation (PXF) was diagnosed by the presence
      of typical white deposits on the anterior lens surface; additional sites included
      the cornea, iris, anterior vitreous face, posterior capsule, and intraocular lens
      in cataract-operated eyes and changes in the angle determined through gonioscopy,
      including increased pigmentation, PXF deposition, and PXF material within the
      angle. CONCLUSIONS: The prevalence (95% confidence interval) of PXF was 6.0%
      (5.3, 6.6). The prevalence increased with age (P <.001) and was greater in males
      (P =.01). Of subjects with PXF, 25.7% remained bilaterally blind after best
      correction; 89.3% of this bilateral blindness was the result of cataracts. The
      prevalence of glaucoma among subjects with PXF was 7.5%; exfoliation was present
      in 26.7% of those identified as primary open-angle glaucoma. On multivariate
      analysis, increasing age and male gender were significantly associated with PXF.
      Pseudoexfoliation appears to be a relatively common disorder in older individuals
      in southern India. Ophthalmologists in India may wish to focus on the detection
      of PXF, especially considering the relatively large burden of cataracts in this
      population, the risks for operative complications related to PXF, and the fact
      that PXF may be used as a marker to aid in the detectection of glaucoma.

PMID- 12788124
TI  - Analysis of macular volume in normal and glaucomatous eyes using optical
      coherence tomography.
AB  - PURPOSE: To evaluate macular volume in normal and glaucomatous eyes using optical
      coherence tomography (OCT). DESIGN: Case control study. METHOD: The authors
      assessed 272 eyes of 164 subjects as part of an institutional study at New
      England Eye Center in Boston, Massachusetts; 202 eyes were in the study group and
      70 eyes in the control group. Eyes were categorized as normal (70 eyes of 43
      subjects), glaucoma suspect (70 eyes of 44 subjects), early glaucoma (70 eyes of
      47 subjects), or advanced glaucoma (62 eyes of 43 subjects). Subjects underwent
      analysis with the commercially available OCT1 unit. Optical coherence tomography
      macular neurosensory retinal thickness maps were used to calculate macular volume
      for comparison to Humphrey visual field testing, intraocular pressure
      measurement, and stereo biomicroscopy of the optic nerve head and nerve fiber
      layer. RESULTS: Using repeated measures regression, macular volume in normal
      (2.37 +/- 0.11 mm(3)) glaucoma suspect (2.33 +/- 0.16 mm(3)), and early glaucoma
      eyes (2.27 +/- 0.13 mm(3)) was significantly greater than in eyes with advanced
      glaucoma (2.12 +/- 0.23 mm(3), P =.0001, P =.0001, and P =.0008, respectively).
      Macular volume in normal eyes was significantly greater than in early glaucoma
      eyes (P =.01). CONCLUSIONS: Optical coherence tomography retinal macular volume
      correlates with known structural defects of glaucoma, providing a potential
      objective and quantitative parameter for evaluation. Our data show a significant
      difference in macular volume between normal, glaucoma suspect, and early glaucoma
      eyes, compared with advanced glaucomatous eyes as well as between normal and
      early glaucomatous eyes. This correlates with a trend of decreasing macular
      volume in eyes with more advanced disease.

PMID- 12788125
TI  - Relationship between human leukocyte antigen status and proliferative diabetic
      retinopathy in patients with younger-onset type 1 diabetes mellitus.
AB  - PURPOSE: To investigate the relationship between human leukocyte antigen (HLA)
      status and proliferative diabetic retinopathy (PDR) to assess the genetic basis
      of PDR in younger type 1 diabetic patients. DESIGN: Retrospective, nonrandomized,
      comparative trial. METHOD: Patients who were diagnosed with type 1 diabetes under
      30 years of age (range, 13-28) and had a disease duration of more than 10 years
      were studied. The patients were divided into two groups: 30 patients who had
      undergone vitreous surgery younger than 40 years old (the PDR group) and 50
      patients without retinopathy (the non-DR group). The duration of diabetes and the
      level of glycemic control were matched between the two groups. The control group
      consisted of 50 healthy patients. HLA-A, -B, -C, -DR, and -DQ typing of blood
      samples was done using the standard microcytotoxicity method. RESULTS: The
      frequency of HLA-B62, Cw4, and DQ4 was significantly higher in the PDR group than
      in the non-DR group (P =.0020, P =.048, and P =.0026, respectively). The Cw4-DR4
      DQ4 haplotype frequency was significantly higher in the PDR group than in the
      control group and the non-DR group (P =.0059). CONCLUSIONS: Our results suggests
      that HLA-B62, Cw4, and DQ4 may be useful for predicting the prognosis of
      retinopathy in patients with younger-onset type 1 diabetes.

PMID- 12788126
TI  - Is there an association between cataract surgery and age-related macular
      degeneration? Data from three population-based studies.
AB  - PURPOSE: To determine whether cataract surgery is associated with an increased
      prevalence of age-related macular degeneration (AMD) in three independent
      population-based data sets. DESIGN: Cross-sectional study. METHOD: Data were used
      from the Salisbury Eye Evaluation (2,520 subjects from Salisbury, Maryland, aged
      65 to 84 years), the Proyecto VER (4,774 Hispanic subjects from Arizona aged 40
      years and older), and the Baltimore Eye Survey (4,396 subjects from Baltimore,
      Maryland, aged 40 and older). The main outcome measure was AMD as determined by
      retinal photographs or clinical examination. RESULTS: A history of cataract
      surgery was associated with an increased prevalence of late AMD in all three data
      sets after adjusting for age, race, sex, and smoking, but odds ratios (OR) were
      not individually statistically significant. The OR for the combined analysis was
      1.7 (95% confidence interval: 1.1-2.6). Having a severe cataract in the eye was
      also associated with a slightly higher prevalence of late AMD, although the
      combined OR was not statistically significant (OR = 1.4; 95% confidence interval,
      0.8%-2.4). Overall, increasing time since cataract surgery was not associated
      with late AMD. CONCLUSIONS: A history of cataract surgery may be associated with
      an increased prevalence of late AMD. However, having a severe cataract in the eye
      may also be associated with a higher prevalence of late AMD. Additional research
      is needed to investigate whether a causal relationship exists between cataract
      surgery and AMD or whether this relationship is due to residual confounding or
      bias.

PMID- 12788127
TI  - Selective occlusion of subfoveal choroidal neovascularization in pathologic
      myopia using a new technique of ingrowth site treatment.
AB  - PURPOSE: To evaluate the visual and angiographic effects as well as optical
      coherence tomography findings after a new technique of ingrowth site treatment of
      subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia with
      the use of indocyanine green (ICG)-mediated photothrombosis. DESIGN:
      Interventional, noncomparative case series. METHOD: In the setting of a tertiary
      referral center, patients with pathologic myopia in whom fluorescein and
      conventional ICG angiography demonstrated distinct CNV vessels supplying the
      subfoveal neovascular complex were submitted to focal ingrowth site treatment
      using a new therapeutic modality termed ICG-mediated photothrombosis. Prospective
      evaluation including visual acuity assessment, fluorescein and ICG angiography,
      and optical coherence tomography (OCT) evaluation was performed at weeks 1, 12,
      24, and 48 after treatment. RESULTS: Six consecutive patients (six eyes) had
      treatment using a single session of ICG-mediated photothrombosis at the CNV
      ingrowth site. Obliteration of the entire neovascular complex was achieved
      immediately after treatment in all patients. At last follow-up, visual acuity
      improvement of 1 or more Early Treatment Diabetic Retinopathy Study lines was
      observed in five of six patients, and fluorescein angiography showed an absence
      (four eyes) or minimal leakage (two eyes) from CNV. Indocyanine green angiography
      demonstrated selective obliteration of the neovascular complex. Accordingly,
      reduction of retinal edema was observed in the OCT evaluation in all patients.
      There was no significant complication related to the procedure. CONCLUSIONS: The
      use of lower irradiances of 810- nm continuous light application and intravenous
      ICG infusion for neovascular ingrowth site photothrombosis induced selective CNV
      hypoperfusion, as demonstrated by fluorescein and ICG angiography in patients
      with pathologic myopia. These findings were either consistent with the visual
      acuity improvement observed in five of six patients or with the partial
      restoration of the retinal architecture seen in OCT evaluation 12 months after
      treatment.

PMID- 12788128
TI  - Special considerations in the evaluation and management of uveitis in children.
AB  - PURPOSE: To review issues related to the diagnosis, examination, and treatment of
      children with uveitis that are important for ophthalmologists. DESIGN: Literature
      review. METHOD: A review was made of pertinent reports from the medical
      literature, with commentary based on the authors' experiences and on discussions
      at an international workshop. RESULTS: There are differences between children and
      adults in the differential diagnosis and manifestations of uveitis that should be
      considered during evaluation. There may be a higher risk of some ocular
      complications such as uveitic glaucoma, and the presence of other unique
      complications, such as amblyopia, in young patients during follow-up. With regard
      to treatment, children with uveitis may have unique dosing requirements and drug
      associated risks such as growth retardation with systemic corticosteroids that
      must be considered. Examination and treatment may also be more difficult with
      children because of problems with patient cooperation. CONCLUSIONS: There are
      unique patient care issues associated with uveitis in children that must be
      considered by care providers. Attention to these issues will improve the well
      being of this patient population.

PMID- 12788129
TI  - Arthritis and uveitis in children. A pediatric rheumatology perspective.
AB  - PURPOSE: We describe important characteristics of the chronic arthritides of
      childhood associated with anterior uveitis. DESIGN: Literature review and
      commentary based on the investigators' experiences. METHOD: A review of pertinent
      publications provides a background of current understanding of those forms of
      childhood arthritis that are of interest to ophthalmologists caring for children.
      Recommendations regarding screening for asymptomatic anterior uveitis in this
      patient group are reviewed, and current advances in therapy are noted. A new
      classification of childhood arthritis is compared with existing classifications.
      RESULTS: Uveitis complicates several forms of juvenile idiopathic arthritis
      (oligoarthritis, rheumatoid factor-negative polyarthritis, psoriatic arthritis,
      and enthesitis-related arthritis). Uveitis is a complication in up to 30% of
      children with chronic arthritis, particularly in those with oligoarticular
      disease. CONCLUSIONS: Visual prognosis is guarded for children with chronic
      arthritis and uveitis. Surveillance and early therapy are important factors for
      ensuring a good outcome.

PMID- 12788130
TI  - Intermediate uveitis in childhood preceding the diagnosis of multiple sclerosis:
      a 13-year follow-up.
AB  - PURPOSE: An association between multiple sclerosis during childhood and uveitis
      is exceptionally rare. This is a report of a female patient who presented at the
      age of 8 years with bilateral intermediate uveitis and whose final diagnosis of
      multiple sclerosis was made at age 21 years. DESIGN: Case report. METHOD:
      Retrospective chart review of a 13-year follow-up history. RESULTS: Over 10 years
      our patient was treated systemically and underwent bilateral vitrectomy to reduce
      permanent side effects. Owing to good visual function and low inflammatory signs,
      systemic therapy was stopped. Multiple sclerosis was diagnosed at the age of 21,
      after a 13-year history of uveitis and after 3 years without medication.
      CONCLUSIONS: In the constellation of uveitis in childhood and later diagnosis of
      multiple sclerosis, the outlined therapy provided good functional results.
      Moreover, it may have delayed the manifestation of the underlying disease for 13
      years.

PMID- 12788131
TI  - Ocular involvement in children with candidemia.
AB  - PURPOSE: To evaluate ocular findings in hospitalized children with systemic
      Candida species infection. DESIGN: Retrospective review of inpatient hospital
      consultations. METHOD: Inpatient hospital consultations performed by a pediatric
      ophthalmology service over a 30-month period were reviewed. RESULTS: Of 600
      consultations performed by the service, 30 were to rule out ocular findings in
      patients with suspected or known candida infection. No patients had ocular
      findings consistent with endophthalmitis or chorioretinitis. One patient had
      nonspecific findings of multisystem organ failure, and one had vascular findings
      secondary to elevated pulmonary venous pressures. CONCLUSIONS: In contrast to the
      results of studies performed 10 to 15 years ago, ocular involvement is highly
      unusual in children with candidemia, but such consultations account for a
      substantial workload. Further attention to risk factors associated with ocular
      infection is warranted.

PMID- 12788132
TI  - Eye findings of diffuse unilateral subacute neuroretinitis and multiple choroidal
      infiltrates associated with neural larva migrans due to Bbaylisascaris procyonis.
AB  - PURPOSE: To report childhood infection with Baylisascaris procyonis (raccoon
      round worm) manifesting as diffuse unilateral subacute neuroretinitis (DUSN) and
      choroidal infiltrates in association with neurologic disease (neural larva
      migrans). METHOD: Observational case series, one with eye manifestations of DUSN,
      the other with choroidal infiltrates, both with severe neurologic degeneration.
      RESULTS: Indirect immunofluorescence assays on serum and cerebrospinal fluid were
      positive for B. procyonis in one and serially positive and increasing in the
      other. Both children had a history of pica and raccoon exposure. CONCLUSIONS:
      Baylisascaris procyonis infection is associated with two cases of severe
      neurologic degeneration with ocular lesions: DUSN and choroidal infiltrates.
      Although B. procyonis is known to cause DUSN, these cases indicate that
      concomitant ocular migration may accompany neural larva migrans. These are the
      third and forth cases in the US literature of neural larva migrans due to B.
      procyonis with eye findings.

PMID- 12788133
TI  - Cataract after minor trauma in a young patient with an iris-fixated intraocular
      lens for high myopia.
AB  - PURPOSE: To report a case of traumatic cataract in a young patient with an iris
      fixated phakic intraocular lens (PIOL). DESIGN: Interventional case report.
      METHOD: A 32-year-old woman with bilateral iris-fixated PIOLs for high myopia
      presented with a cortical cataract 2 weeks after minor ocular trauma. Ultrasound
      biomicroscopy and endothelial cell count were performed before and after cataract
      surgery. RESULTS: The distance between the PIOL and the crystalline lens was 0.82
      mm; the distance between the PIOL and the corneal endothelium was 2.30 mm.
      Endothelial cell count was 2,500 cells/mm(2) before surgery and 2,476 cells/mm(2)
      at 1 year follow-up. CONCLUSIONS: Patients with iris-fixated PIOLs are at risk of
      rapid cataract progression after minor ocular traumatism.

PMID- 12788134
TI  - Corticosteroid-induced modulation of acute syphilitic posterior placoid
      chorioretinitis.
AB  - PURPOSE: To report a case of corticosteroid-induced modulation of acute
      syphilitic posterior placoid chorioretinitis. DESIGN: Interventional case report.
      METHOD: A 38-year-old homosexual male who presented with a unilateral uveitis
      secondary to syphilis developed large placoid macular lesions after treatment
      with oral prednisone that resolved when the corticosteroids were discontinued.
      RESULTS: A cause-and-effect relationship was demonstrated between oral prednisone
      and the appearance of acute syphilitic posterior placoid chorioretinitis.
      CONCLUSIONS: The clinical appearance of posterior placoid chorioretinitis in
      syphilis may be modulated by the immune status of the patient.

PMID- 12788135
TI  - Removal of the internal limiting membrane under perfluorocarbon liquid to treat
      macular-hole-associated retinal detachment.
AB  - PURPOSE: To demonstrate the advantages and efficacy of internal limiting membrane
      removal under perfluorocarbon liquid in macular-hole-associated retinal
      detachment. DESIGN: Interventional case series. METHOD: Four patients with
      macular-hole-associated retinal detachment underwent pars plana vitrectomy,
      retinal reattachment with endodrainage through the macular hole, perfluoro-n
      octane injection to seal the macular hole, indocyanine green injection under the
      perfluoro-n-octane bubble and removal of the indocyanine green-stained internal
      limiting membrane. Visual acuity and anatomic results were recorded, with a mean
      follow-up period of 18 months. RESULTS: Postoperatively, the retina was
      reattached in all four patients and closure of the macular hole was achieved in
      three eyes. Visual acuity improved in all eyes. CONCLUSIONS: In retinal
      detachment resulting from macular hole, staining of the internal limiting
      membrane with indocyanine green injected under perfluoro-n-octane can facilitate
      peeling of the membrane without exertion of excessive retinal traction and may
      prevent passage of indocyanine green into the subretinal space.

PMID- 12788136
TI  - Therapeutic deep lamellar keratoplasty for cornea perforation.
AB  - PURPOSE: To present the efficacy of performing deep lamellar keratoplasty as an
      emergency measure following perforation of the cornea. DESIGN: Interventional
      case report. METHOD: Deep lamellar keratoplasty was performed in two cases of
      perforated cornea. Following incarceration of the iris within the perforated
      area, The Descemet membrane was exposed except for strands of stroma surrounding
      the perforation. A fresh donor cornea stripped of the Descemet membrane was then
      sutured in place. RESULTS: Both cases have attained clear corneas in areas other
      than the original perforation. CONCLUSIONS: Deep lamellar keratoplasty is a safe
      technique for the treatment of cornea perforation.

PMID- 12788137
TI  - Treatment of choroidal melanoma using photodynamic therapy.
AB  - PURPOSE: To InternetAdvance publication at ajo.com Feb 26, 2002. investigate the
      effect of photodynamic therapy using verteporfin on choroidal melanoma. DESIGN:
      Interventional case series. METHOD: Four patients with choroidal melanoma who
      showed recurrence or no response after previous brachytherapy and transpupillary
      thermotherapy were treated with photodynamic therapy. RESULTS: One tumor
      decreased in size and remained stable for 18 months. One tumor had no growth for
      11 months. Two melanomas continued to grow, necessitating enucleation.
      CONCLUSIONS: Of the four eyes that had failed conventional therapies, two would
      have been salvaged (to date) with photodynamic therapy. However, additional
      studies are needed to determine if photodynamic therapy can play a role in the
      management of choroidal melanoma.

PMID- 12788138
TI  - Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization
      in children.
AB  - PURPOSE: To report the safety of photodynamic therapy with verteporfin in three
      children. DESIGN: Retrospective interventional noncomparative case series.
      METHOD: Children identified from all patients treated with verteporfin therapy at
      a university-based practice had records reviewed for adverse retinal or systemic
      events. RESULTS: Patients aged 11, 11, and 13 years, with subfoveal idiopathic
      choroidal neovascularization (CNV) received verteporfin therapy with no ocular
      complications recognized either immediately after the procedure or during the
      follow-up from 7 to 12 months. Treatment resulted in cessation of fluorescence
      leakage from CNV by the last follow-up visit in two patients and reduced leakage
      from the lesion in one. The visual acuity change was + 4, +7, and 0 lines.
      CONCLUSIONS: Verteporfin therapy in three children with subfoveal CNV was
      associated with stable or improved vision during short-term follow-up in the
      absence of serious ocular or systemic adverse events.

PMID- 12788139
TI  - The correlation between various types of intraocular lens and laser wavelength.
AB  - PURPOSE: To analyze effects of the composition and the color of intraocular
      lenses (IOLs) on laser wavelength. DESIGN: A case control study. METHOD: Laser
      light rays at wavelengths ranging from 0.1 to 0.5 W were directed at a
      polymethymethacrylate ocular model fitted consecutively with three types of IOLs
      at various refractive powers. A laser detector was placed on the model beneath
      the lenses. The laser beam was passed through the IOLs and the output measured by
      a sensor. Attenuation rate was calculated. RESULTS: The colored IOL caused
      significantly more attenuation than did the noncolored IOLs (p <.01). A 30
      diopter colored IOL showed an attenuation rate of up to 15% at a wavelength of
      488 + 514 nm. CONCLUSIONS: Consideration of the wavelength and the output of a
      laser for a particular IOL is required when laser photocoagulation of the retina
      is performed in patients with pseudophakia.

PMID- 12788140
TI  - Trypan blue-assisted peeling of the internal limiting membrane during macular
      hole surgery.
AB  - PURPOSE: To evaluate the outcome of surgeries for macular holes using trypan blue
      to facilitate delamination of the internal limiting membrane. DESIGN: A
      retrospective series of 18 patients. METHOD: All patients underwent a three-port
      pars plana vitrectomy with internal limiting membrane delamination using trypan
      blue 0.06% to assist visualization. The main outcome measures were postoperative
      visual acuity and clinically evident retinal pigment epithelial changes. RESULTS:
      The median preoperative visual acuity was 20/200, and the median postoperative
      visual acuity was 20/70. All but one macular hole were closed after surgery
      (94%). At the last recorded follow-up, 10 patients (56%) had improved visual
      acuity of at least two chart lines. No adverse reaction related to trypan blue
      was observed up to 1 year postsurgery. CONCLUSIONS: Trypan blue staining of
      internal limiting membrane may accomplish more complete dissections of the
      internal limiting membrane and better surgical and visual outcomes.

PMID- 12788141
TI  - Migration and apparent disappearance of silicone tube following treatment of
      nasolacrimal duct obstruction.
AB  - PURPOSE: To describe the unusual complication of migration and apparent
      disappearance of silicone tubes following intubation of the lacrimal drainage
      system. DESIGN: Interventional case reports. METHOD: Report of two patients with
      an unusual tube migration process. RESULTS: Silicone stents migrated nasally,
      with healing of the erosion tract in the wake of the migrating tube. One tube
      became completely internalized. CONCLUSIONS: Meticulous inspection of the medial
      canthal area in patients with suspected spontaneous extrusion of silicone stents
      from the lacrimal drainage system is warranted. Examination under anesthesia and
      nasal endoscopy may help locate tubes in cases of suspected nasal migration.

PMID- 12788142
TI  - Ruptured retinal arterial macroaneurysm associated with a stage IV macular hole.
AB  - PURPOSE: To report a case of stage IV macular hole associated with ruptured
      retinal arterial macroaneurysm. DESIGN: Observational case report. METHOD: The
      patient's clinical, angiographic, and ophthalmic coherent tomography data were
      reviewed. RESULTS: A stage IV macular hole was observed in association with a
      ruptured retinal arterial macroaneurysm in a 79-year-old patient. After
      vitrectomy surgery, the macular hole closed and vision improved from counting
      fingers to 20/100. CONCLUSIONS: Macular hole associated with ruptured retinal
      macroaneurysm can be closed successfully to result in improved vision.

PMID- 12788143
TI  - Epiretinal membrane surgery assisted by trypan blue.
AB  - PURPOSE: To evaluate patient outcome following epiretinal membrane surgery using
      trypan blue to facilitate visualization and delamination. DESIGN: A retrospective
      noncomparative review of 23 patients. METHOD: Patients underwent a three-port
      pars plana vitrectomy with delamination using trypan blue 0.06%. RESULTS: The
      median preoperative visual acuity was 20/100. The median postoperative visual
      acuity was 20/60. Seventeen patients (74%) improved their visual acuity by at
      least 2 chart lines. No adverse reaction related to trypan blue was observed up
      to 1 year postoperatively. CONCLUSIONS: Trypan blue staining of the epiretinal
      membrane facilitated visualization and delamination without any signs of
      toxicity.

PMID- 12788144
TI  - Spontaneous regression of choroidal metastasis from renal cell carcinoma.
AB  - PURPOSE: To describe a patient with choroidal metastasis from renal cell
      carcinoma that spontaneously regressed after nephrectomy. DESIGN: Interventional
      case report. METHOD: A 48-year-old Hispanic woman presented with reduced vision
      in the left eye attributable to an elevated choroidal lesion and associated
      exudative retinal detachment. Oncology workup revealed a left kidney renal cell
      carcinoma with pulmonary metastases. The patient underwent primary nephrectomy,
      without specific treatment of choroidal or pulmonary metastases. RESULTS: The
      metastatic choroidal lesion regressed and the retinal detachment completely
      resolved, as evidenced by fundus photographs and ultrasonography. CONCLUSIONS:
      Choroidal metastasis from renal cell carcinoma may spontaneously regress after
      removal of the primary tumor.

PMID- 12788146
TI  - Posttraumatic exogenous Nocardia endophthalmitis.
AB  - PURPOSE: To report a case of posttraumatic exogenous Nocardia endophthalmitis.
      DESIGN: Interventional case report. METHOD: A 46-year-old man presented with
      counting fingers vision, severe eye pain, hypopyon, and an iris mass consistent
      with endophthalmitis following a penetrating injury to the left eye. RESULTS:
      Despite oral fluconazole and repeated intravitreal injections of vancomycin,
      gentamicin, and amphotericin B, the eye remained painful with a persistent
      hypopyon and recurrent iris masses. Cultures of the vitreous and iris masses
      remained negative for organisms. Despite vitrectomy and sector iridectomy of the
      iris mass with repeat injections of intravitreal antibiotics, the patient
      continued to have severe pain, poor vision, and developed new iris masses.
      Enucleation cultures confirmed Nocardia asteroides. CONCLUSIONS: Posttraumatic
      exogenous Nocardia endophthalmitis is extremely rare, and its clinical signs can
      mimic a fungal infection.

PMID- 12788145
TI  - Optical coherence tomography findings in nicotinic acid maculopathy.
AB  - PURPOSE: To report optical coherence tomography findings in nicotinic acid
      maculopathy. DESIGN: Observational case report. METHOD: The patient was examined
      with ophthalmoscopy, fluorescein angiography, and optical coherence tomography.
      RESULTS: A 71-year-old man presented with bilateral decreased visual acuity with
      metamorphopsia. Optical coherence tomography demonstrated cystoid spaces in the
      outer plexiform layer and inner nuclear layer. Fluorescein angiography did not
      show leakage. Two weeks after stopping the nicotinic acid, the cystoid spaces
      resolved. CONCLUSIONS: Niacin maculopathy causes cystoid spaces in the inner
      nuclear and outer plexiform layers that resolve with discontinuation of the drug.

PMID- 12788147
TI  - Macular dystrophy in a Japanese family with fundus albipunctatus.
AB  - PURPOSE: To report a Japanese family with fundus albipunctatus and macular
      dystrophy associated with a mutation in the 11-cis retinol dehydrogenase (RDH5)
      gene. DESIGN: Observational case report. METHOD: Ophthalmic examinations and DNA
      analysis were performed. RESULTS: The fundi of a 56-year-old man and his 51-year
      old sister showed numerous yellow-white punctata. He also had bull's-eye
      maculopathy and prepappillary arterial loops, whereas she did not, and his best
      corrected visual acuity was impaired, whereas hers was normal. Their kinetic
      visual fields did, however, show central or paracentral scotoma, and both had
      tritanomalous color vision. Their scotopic electroretinograms were typical of
      fundus albipunctatus, and photopic electroretinograms were significantly reduced.
      A homozygous Gly107Arg mutation in the RDH5 gene was detected in both siblings.
      CONCLUSIONS: We suggest that the macular dystrophy is caused by the RDH5 gene
      mutation as a phenotype variation in fundus albipunctatus.

PMID- 12788148
TI  - Choroidal neovascular membrane associated with optic nerve coloboma in a patient
      with CHARGE association.
AB  - PURPOSE: To report a patient with CHARGE association (coloboma, heart disease,
      choanal atresia, growth retardation, genital hypoplasia, and ear abnormalities)
      who developed a choroidal neovascular membrane in association with an optic nerve
      coloboma. DESIGN: Interventional/observational case report. METHOD: A 21-month
      old boy with CHARGE association developed a grayish choroidal neovascular
      membrane associated with lipid exudation, subretinal fluid, and retinal
      hemorrhage at the temporal edge of his right optic nerve coloboma. RESULTS: The
      patient underwent transpupillary diode laser of the choroidal neovascular
      membrane. Five months later, it and the serous retinal detachment had resolved.
      CONCLUSIONS: Patients with CHARGE association may develop choroidal neovascular
      membrane with serous retinal detachments in association with optic nerve
      colobomas. These neovascular membranes may be treated successfully with
      transpupillary diode laser.

PMID- 12788163
TI  - Consolidation radiotherapy in the treatment of advanced Hodgkin's disease: is it
      dead?

PMID- 12788149
TI  - A six-month randomized clinical trial comparing the IOP-lowering efficacy of
      bimatoprost and latanoprost in patients with ocular hypertension or glaucoma.

PMID- 12788164
TI  - How one defines intensity-modulated radiation therapy.

PMID- 12788165
TI  - Long-term changes in pulmonary function tests after definitive radiotherapy for
      lung cancer.
AB  - PURPOSE: To evaluate the long-term changes in pulmonary function tests (PFTs) in
      patients surviving at least 2 years after definitive radiotherapy (RT) for
      unresectable lung cancer. METHODS AND MATERIALS: Between 1992 and 2000, 277
      patients were enrolled in a prospective clinical study to relate RT-induced
      changes in lung function with dosimetric and functional metrics. Of these, 128
      received definitive RT for lung cancer, and 13 of these had follow-up PFTs for
      approximately >/=2 years without evidence of recurrent or progressive cancer.
      PFTs were obtained before RT and approximately every 6 months after RT. The
      results were evaluated on the basis of each study's "percentage of predicted" of
      normal values (i.e., adjusted for age, gender, height), and a patient's
      sequential examinations were compared with their initial study and a percentage
      of the baseline value was calculated. Follow-up PFTs were available for a median
      of 38 months (range 23-95). The median patient age was 65 years (range 40-74), 6
      patients were men, and 10 were white. Most had Stage T2-T4 and N2-N3. The median
      RT dose was 71.4 Gy (range 60-73), 6 had twice-daily RT. Four patients received
      chemotherapy, one concurrent and three neoadjuvant. None of the patients
      continued to smoke after their treatment. The median pre-RT PFT results were
      (percentage of predicted) forced expiratory volume in 1 s, 67% (range 24-121);
      forced vital capacity, 72% (range 45-116); and diffusing capacity of lung for
      carbon monoxide, 70% (range 41-129). RESULTS: At 6 months, all PFT values had
      declined, with some stabilization by 1 year. However, after 1 year, a gradual
      reduction occurred in all three parameters. Ten patients (77%) developed RT
      induced respiratory symptoms (2 cough only, 8 dyspnea) at 2-21 months (median 5)
      after treatment. Two patients required inhalers, another required long-term
      steroids and oxygen. Of the 8 patients with dyspnea, 7 had an increase in
      symptoms beyond 2 years. No patient died of RT-induced pulmonary insufficiency.
      CONCLUSION: RT caused a decline in PFTs that was apparent at 6 months and
      continued well beyond 1 year. The continued decline in PFTs is suggestive of
      progressive/evolving RT-induced lung injury. "Late" pulmonary symptoms have also
      occurred in these patients. Because of the high mortality rate of unresectable
      lung cancer, few patients can be evaluated for long-term analysis. Additional
      studies and pooling of data from multiple institutions may help to clarify better
      the long-term impact of RT on pulmonary function in this subset of patients.

PMID- 12788166
TI  - Postoperative radiotherapy increases locoregional control of patients with stage
      IIIA non-small-cell lung cancer treated with induction chemotherapy followed by
      surgery.
AB  - PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in
      patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated
      with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We
      retrospectively reviewed the treatment records of 98 patients (58 men and 40
      women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who
      were treated with induction chemotherapy followed by surgery at our institution
      between January 1990 and December 2000. Patients were grouped by treatment
      (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and
      nodal classification. The rates of local control (LC), disease-specific survival,
      disease-free survival, and overall survival (OS) were calculated using the Kaplan
      Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage
      IIIA. The clinical disease stage and N stage were significantly greater in those
      patients who underwent RT than in those who did not; however, no statistically
      significant differences were identified in the additional characteristics between
      those receiving and not receiving RT within each stage or nodal group. The
      overall 5-year actuarial LC rate was 81% in the RT group and 54% in the
      chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly
      improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%,
      p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30%
      with RT vs. 49% without) for all patients or for patients with Stage IIIA
      disease. The disease-specific survival and disease-free survival rates did not
      differ between the treatment groups. Patients who responded to induction
      chemotherapy had a significantly greater 5-year OS rate (49%) than did those with
      stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in
      patients with Stage IIIA NSCLC treated with induction chemotherapy followed by
      surgery significantly improved LC without improving OS. Significantly improved
      survival was observed in all patients who responded to induction chemotherapy
      compared with those with stable or progressive disease.

PMID- 12788167
TI  - Twenty-year follow-up study of long-term survival of limited-stage small-cell
      lung cancer and overview of prognostic and treatment factors.
AB  - PURPOSE: To predict the long-term survival results of clinical trials earlier
      than using actuarial methods and to assess the factors predictive of long-term
      cure in patients with limited-stage small-cell lung cancer. METHODS AND
      MATERIALS: Between 1981 and 1998, 1417 new cases of small-cell lung cancer were
      diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated
      with curative intent. They were followed to the end of February 2002. A
      parametric lognormal statistical model was retrospectively validated to determine
      whether long-term survival rates could be estimated several years earlier than is
      possible using the standard life-table actuarial method. RESULTS: The survival
      time of the uncured group followed a lognormal distribution. Four 2-year periods
      of diagnosis were combined, and patients were followed as a cohort for an
      additional 2 years. The estimated 10-year cause-specific survival rate was 13% by
      the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific
      survival rate was 15% +/- 3%. The data also showed that the absence of
      mediastinal lymphadenopathy and higher chest radiotherapy dose were significant
      prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients
      given prophylactic cranial irradiation, a higher biologically effective dose to
      the brain did not improve survival or decrease the incidence of brain metastases.
      CONCLUSION: The lognormal model has been validated for the estimation of survival
      in patients with limited-stage small-cell lung cancer. A higher biologically
      effective dose to the brain did not improve survival or decrease the incidence of
      brain metastases.

PMID- 12788168
TI  - Analysis of treatment results in advanced Hodgkin's disease: the case for
      adjuvant radiotherapy.
AB  - PURPOSE: To assess the treatment results in patients with advanced Hodgkin's
      disease in a single center and to evaluate the clinical and therapeutic
      prognostic factors, including verification of the significance of the prognostic
      score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients
      with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of
      six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine,
      and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV])
      followed by irradiation (RT) in patients with an indication for RT (84 patients).
      Chemotherapy was then continued for another two cycles. The indications for
      consolidation RT included bulky disease and/or partial response after six cycles
      of chemotherapy. In 31 patients, extended-field RT was performed, and in 53,
      limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The
      median follow-up was 78 months. Complete remission after whole treatment was
      achieved in 88.7% of patients. The actuarial overall survival rate was 78% and
      71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years,
      respectively. The independent adverse prognostic factors in multivariate analysis
      appeared to be older age, low serum albumin, low serum gammaglobulin, lower
      number of chemotherapy cycles, and no RT. The value of the prognostic score was
      confirmed; the higher the prognostic score, the worse the survival. CONCLUSION:
      In patients with advanced Hodgkin's disease, consolidation RT improved survival.
      The best results were achieved with the use of large-volume RT.

PMID- 12788170
TI  - Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven
      ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery.
AB  - PURPOSE: The loss of expression of NES1, a novel putative tumor suppressor gene,
      is an early marker of breast tumorigenesis. NES1 is expressed in normal breast
      tissue and ductal hyperplasia but is absent or markedly diminished in invasive
      cancer. In cases of ductal carcinoma in situ (DCIS), NES1 expression has been
      shown previously to be present in approximately 50% of specimens. This study
      examined the expression level of NES1 in diagnostic biopsy samples found to
      contain pure DCIS. These data were then correlated with the pathologic findings
      found at definitive local surgery. METHODS AND MATERIALS: Twenty-nine cases with
      initial biopsy showing DCIS without invasive carcinoma followed by subsequent
      reexcision were discovered and archived. Formalin-fixed tissue specimens were
      obtained for analysis. Each biopsy specimen was subjected to hematoxylin-eosin
      staining and reviewed by two pathologists to confirm the diagnosis of pure DCIS.
      NES1 cDNA (1069 bp), including 238 bp of 5' and 3' untranslated region and the
      entire protein-coding region, was cloned into a vector. To generate the antisense
      and sense RNA probes, the plasmid was linearized and the transcription reaction
      was carried out with polymerases T7 and T3, respectively. The detection of in
      situ hybridization probes was performed using an mRNAlocator-Biotin Kit. Staining
      was characterized as negative (0/1+) or positive (2+/3+). Subsequent to an
      initial biopsy diagnosis of DCIS, all cases had a definitive surgical procedure.
      Detailed sectioning of the resultant tissue was performed and subjected to
      hematoxylin-eosin staining to determine the presence or absence of invasive
      carcinoma. RESULTS: The initial diagnostic biopsy specimens showed that 17 of 17
      high-grade, 3 of 7 intermediate-grade, and 3 of 5 low-grade DCIS specimens were
      negative for NES1 expression. Of the 6 cases of DCIS found to be positive for
      NES1 expression, none (0%) were subsequently found to have invasive carcinoma at
      definitive surgery. In contrast, the loss of NES1 expression in the initial
      diagnostic biopsy was associated with a 40% incidence of invasive carcinoma at
      definitive surgery. Additional stratification by nuclear grade showed invasive
      carcinoma in 5 (83%) of 6 NES1-negative, low- to intermediate-grade DCIS (p
      </=0.01) and 4 (24%) of 17 NES1-negative, high-grade DCIS (p </=0.05).
      CONCLUSION: These results show that a lack of NES1 expression in DCIS identified
      at the diagnostic biopsy predicts for a high risk of invasive cancer in the
      definitive surgical specimen. The predictive value of NES1 expression appears to
      be particularly relevant for low- and intermediate-grade DCIS.

PMID- 12788169
TI  - Does bulky disease at diagnosis influence outcome in childhood Hodgkin's disease
      and require higher radiation doses? Results from the German-Austrian Pediatric
      Multicenter Trial DAL-HD-90.
AB  - PURPOSE: The identification of risk factors is required for risk-adapted
      treatment strategies in the treatment of Hodgkin's disease. To assess the
      influence of bulky disease at diagnosis as compared with other risk factors on
      event-free survival (EFS) in pediatric Hodgkin's disease such as stage, B
      symptoms, number of involved lymph node regions, histology, and remission status
      after chemotherapy, we analyzed the outcome of 552 patients treated with a risk
      adapted treatment strategy consisting of OPPA(OEPA)/COPP (vincristine,
      procarbazine, etoposide, prednisone, adriamycin, cyclophosphamide) and involved
      field radiotherapy. METHODS AND MATERIALS: Between 1990 and 1995, 578 patients
      with primary Hodgkin's disease (HD) were enrolled in the German/Austrian
      Pediatric Hodgkin's Disease Study Group (DAL) Multicenter Study (HD-90). Patients
      were stratified into three treatment groups (TGs) for early, intermediate, and
      advanced stage. All patients received induction chemotherapy (CT) with two cycles
      of OEPA for boys and two cycles of OPPA for girls. Patients in TG2 and TG3
      received another two or four cycles, respectively, of COPP. Chemotherapy was
      followed by involved-field radiotherapy. The radiation field, which was
      prescribed by the study center, was treated with a dose of 25 Gy/25 Gy/20 Gy
      (TG1/TG2/TG3), and in case of insufficient remission with a local boost of 5 Gy
      to 10 Gy. The following prognostic factors were analyzed with regard to their
      impact on EFS: bulky disease, mediastinal tumor, number of involved lymph node
      regions, histology, treatment group, B-symptoms, sex, age, and remission status
      after chemotherapy. RESULTS: Significant univariate predictive factors for the
      EES were: nodular sclerosis type 2 (NS2) histology (relative risk [RR] 3.43; p =
      0.0002), presence of B-symptoms (RR 2.70; p = 0.0014), number of involved regions
      (1.55; p = 0.019), and treatment groups (RR 1.33; p = 0.017). There was a higher
      risk (RR 1.92; p = 0.040) for patients with bulky compared with nonbulky disease
      (5-year EFS 89.6%/94.6%). In the multiple regression model, only NS2 and B
      symptoms remained strong predictive factors. The remission status after
      chemotherapy did not correlate with EFS (p = 0.66). CONCLUSION: Treatment
      strategies in Hodgkin's disease have an impact on different risk factors. In the
      risk-adapted treatment strategy of the HD-90 study, tumor burden indicated as
      bulky disease or as number of involved lymph nodes loses its importance, whereas
      NS2 histology and B-symptoms have a major impact on treatment outcome. Bulky
      disease at diagnosis might require higher radiation doses only in case of
      insufficient remission.

PMID- 12788171
TI  - Risk factors for regional nodal failure after breast-conserving therapy: regional
      nodal irradiation reduces rate of axillary failure in patients with four or more
      positive lymph nodes.
AB  - PURPOSE: To determine the incidence of, and risk factors for, regional nodal
      failure (RNF) and to evaluate the effectiveness of, and indications for, regional
      nodal irradiation (RNI) in patients with Stage I-II breast cancer treated with
      breast-conserving therapy. METHOD AND MATERIALS: A total of 1500 cases of Stage I
      II breast cancer were treated with breast-conserving therapy between February
      1980 and December 2000. All patients underwent excisional biopsy, and 925 (62%)
      underwent re-excision. Level I-II axillary lymph node dissection was done in 94%
      of patients. The lymph nodes were pathologically involved in 335 patients (22%);
      255 with 1-3 nodes and 80 with >/=4 nodes involved. All patients received whole
      breast irradiation to a median dose of 45 Gy, and 97% received a tumor bed boost
      to a median dose of 61 Gy. Treatment included the breast only in 1309 patients
      (87%), and the breast and regional lymphatics in 191 (13%). RESULTS: With a
      median follow-up of 8.1 years, 35 patients had failure within the regional nodes:
      12 patients (6%) who received RNI and 23 patients (2%) who did not. The 5- and 10
      year rate for any RNF was 1.9% and 2.8%, respectively. The 5 and 10-year rates of
      axillary failure and supraclavicular failure were 0.6% and 1.0% and 0.9% and
      1.6%, respectively. In patients with >/=4 positive lymph nodes, RNI reduced the
      10-year rate of any RNF from 11% to 2% (p = 0.024), the rate of axillary failure
      from 5% to 0% (p = 0.019), and the rate of supraclavicular failure from 11% to 2%
      (p = 0.114). RNI did not affect the rate of axillary failure or supraclavicular
      failure in patients with 1-3 positive nodes. In node-negative patients, the rate
      of RNF was significantly greater if <6 nodes were removed at the time of axillary
      dissection. Multiple clinical, pathologic, and treatment-related factors were
      analyzed for association with RNF. On univariate analysis, RNF was associated
      with the number of nodes excised, number of positive nodes, percentage of
      positive nodes, size of nodal metastasis, presence of angiolymphatic invasion,
      estrogen receptor status, age, systemic chemotherapy, and RNI. Three subsets of
      patients had unusually high rates of RNF, those with >/=67% nodes positive (16%),
      nodal metastasis >/=2.0 cm (44%), or age </=35 years (14%). On multivariate
      analysis, the only significant predictor of RNF was the maximal size of the nodal
      metastasis. RNI did not improve the overall survival for any subset of patients.
      The number of lymph nodes excised had an impact on overall survival, with a 10
      year survival rate of 33%, 65%, and 69% in patients with <6, 6-10, and >10 nodes
      excised, respectively (p = 0.05). CONCLUSION: Failure within the regional lymph
      nodes as an isolated site of first relapse is uncommon in patients with Stage I
      II breast cancer treated with breast-conserving therapy. RNI can significantly
      reduce the rate of RNF (axillary failure) in patients with >/=4 positive lymph
      nodes. The maximal size of the lymph node metastasis was found to be the only
      significant independent predictor of RNF, with nodal metastases >/=2.0 cm
      associated with extremely high regional failure rates. Despite this, young age
      and the extent of axillary dissection (particularly as related to the number of
      positive nodes) also appear to be important and should be considered when
      evaluating patients for RNI. Inadequate axillary dissection was not only
      associated with increased regional failure, but also reduced survival.

PMID- 12788172
TI  - Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by
      local excision and partial breast irradiation by low-dose-rate interstitial
      implant.
AB  - PURPOSE: To evaluate the toxicity of partial breast irradiation (RT) using
      escalating doses of low-dose-rate interstitial implant as the sole adjuvant local
      therapy for selected T1N0 breast cancer patients treated by wide local excision.
      The results of a European Organization for Research and Treatment of Cancer study
      have demonstrated a significant local control benefit using external beam RT to
      65 Gy compared with 50 Gy. Thus, the tolerance of escalating doses of partial
      breast RT should be determined, because this approach may become a standard
      treatment for patients with early-stage breast cancer. METHODS AND MATERIALS:
      Between 1997 and 2001, 48 patients with T1N0M0 breast cancer were enrolled into
      an institutional review board-approved Phase I/II protocol using low-dose-rate
      brachytherapy implants after wide local excision and lymph node staging surgery.
      Brachytherapy was started 3-4 days after surgery at a dose rate of 50 cGy/h,
      using (192)Ir sources evenly spaced to cover 3 cm around the resection margins.
      Typically, 2-3 planes were used, with a median of 14 catheters (range 10-16). The
      total dose was escalated in three groups: 50 Gy (n = 19), 55 Gy (n = 16), and 60
      Gy (n = 13). The implant volume was calculated and used to classify patients into
      quartiles: 76-127 cm(3) (n = 12), 128-164 cm(3) (n = 12), 165-204 cm(3) (n = 12),
      and >204 cm(3) (n = 12). Cosmesis, patient satisfaction, treatment-related
      complications, mammographic abnormalities, rebiopsies, and disease status were
      recorded at each scheduled patient visit. RESULTS: The median follow-up for all
      patients was 23.1 months (range 2-43). Very good to excellent cosmetic results
      were observed in 91.8% of patients. Ninety-two percent of patients were satisfied
      with their cosmetic outcome and said they would choose brachytherapy again over
      the standard course of external beam RT. Six perioperative complications
      occurred: two developed bleeding at the time of catheter removal, two had
      abscesses, one developed a hematoma, and one had a nonhealing sinus tract
      requiring surgical intervention. Significant fibrosis (moderate-to-severe
      scarring and thickening of the skin and breast) was noted in only 4 patients; 1
      had received 55 Gy and 3 had received 60 Gy. Abnormal posttreatment mammograms
      were seen in 19 patients. Eight patients underwent rebiopsy for abnormalities
      found either by mammography or on physical examination; all proved to be fat
      necrosis or post-RT changes. The rebiopsy rates appeared to correlate with doses
      >/=55 Gy (6 [75%] of 8 compared with 29 [60%]of 48 overall) and implant volumes
      >/=128 cm(3) (7 [87.5%] of 8 compared with 36 [75%] of 48 overall). To date, no
      local, regional, or distant recurrences have been observed. CONCLUSION: Low-dose
      rate implants up to 60 Gy were well-tolerated overall. With an implant dose of 60
      Gy, the incidence of posttreatment fibrosis (25%) appeared to be increased. Only
      the long-term follow-up of this and other implant studies will allow an
      understanding of the total radiation dose necessary for tumor control and the
      volume of breast that requires treatment.

PMID- 12788173
TI  - Partial breast brachytherapy after lumpectomy: low-dose-rate and high-dose-rate
      experience.
AB  - PURPOSE: The use of partial breast brachytherapy (PBB) after lumpectomy for
      selected patients with early-stage breast cancer reduces the adjuvant
      radiotherapy treatment time to <1 week. Despite the advantages of accelerated
      treatment, maintaining an acceptable cosmetic outcome is important. In a cohort
      of patients who received low-dose-rate (LDR) or high-dose-rate (HDR) PBB after
      lumpectomy, the clinical characteristics and treatment parameters were analyzed
      to identify predictors for an unfavorable cosmetic outcome. METHODS AND
      MATERIALS: Early-stage breast cancer patients with clear resection margins and 0
      3 positive lymph nodes were eligible for PBB. Uniform guidelines for target
      definition and brachytherapy catheter placement were applied. The HDR PBB dose
      was 34 Gy in 10 fractions within 5 days, and the LDR dose was 45 Gy given at a
      rate of 50 cGy/h. The end points included incidence of radiation recall reaction,
      telangiectasias, and cosmetic-altering fibrosis. RESULTS: Between 1995 and 2000,
      44 patients with early-stage breast cancer received PBB without adjuvant external
      beam radiotherapy after lumpectomy (31 HDR PBB, 13 LDR PBB). After a median
      follow-up of 42 months (range 18-86), all patients remained locally controlled.
      The overall rate of good/excellent cosmetic outcome was 79.6% overall and 90%
      with HDR PBB. Radiation recall reactions occurred in 43% of patients (6 of 14)
      who received adriamycin. LDR PBB and adriamycin were significant predictors for
      late unfavorable cosmetic changes in univariate analysis (p = 0.003 and p =
      0.005, respectively). CONCLUSION: Although a high rate of local control and
      good/excellent cosmetic outcome is provided with HDR PBB, the risk of unfavorable
      cosmetic changes when treated with both LDR PBB and adriamycin is noteworthy.
      This suggests that HDR PBB is preferred in patients for whom adriamycin is
      indicated.

PMID- 12788174
TI  - Intraoperative high-dose-rate 192Ir radical implant in early breast cancer: a
      quality assurance and dosimetry study.
AB  - PURPOSE: To evaluate the variability in catheter length, geometry, and dosimetric
      parameters of radical intraoperative high-dose-rate breasts implant during 7-11
      days. METHODS AND MATERIALS: Simulator X-rays, CT scans, and dosimetric studies
      were repeated on alternate days in 14 consecutive patients treated with radical
      intraoperative two- or three-plane nylon catheter high-dose-rate implant (34 Gy
      in 10 fractions within 5 days). RESULTS: Significant variation was found in
      catheter length, but no major change was noted in implant geometry, homogeneity,
      or inhomogeneity indexes. A variation in length of >5 mm in one or more catheters
      was seen in all patients and >10 mm in 11 patients at any time during the
      implant. Of the 171 catheters in 14 patients, 100 (58%) and 38 (22%) showed a
      variation of >5 mm or >10 mm, respectively. The variation of >10 mm was reduced
      from 32% of catheters in the first 5 patients to 17% in the subsequent 9 patients
      (p = 0.028). Rigid catheter fixation might reduce length variation but may cause
      skin necrosis if the expanding cavity indents the skin for a long period against
      the fixation device. A dose homogeneity index of 0.90 (range 0.85-0.92) and dose
      nonuniformity ratio of 0.20 (range 0.12-0.25) were satisfactory. CONCLUSION: The
      catheter fixation and exit catheter length should be measured daily and if the
      implant is in situ for more than a few days, orthogonal X-rays and, if indicated,
      dosimetry should be repeated at least once.

PMID- 12788175
TI  - Postmastectomy radiotherapy in premenopausal Vietnamese and Chinese women with
      breast cancer treated in an adjuvant hormonal therapy study.
AB  - BACKGROUND: Adjuvant postmastectomy radiotherapy (RT) decreases the risk of local
      recurrence of breast cancer and may increase overall survival (OS). METHODS AND
      MATERIALS: After mastectomy, 656 premenopausal Vietnamese and Chinese women with
      clinical Stage II-IIIA breast cancer, in a clinical trial of adjuvant surgical
      oophorectomy and tamoxifen, were treated with adjuvant RT according to the
      availability in the institution. The short-term disease recurrence and OS
      experience of these 656 women were analyzed using univariate and multivariate
      methods. RESULTS: The 193 patients who did not receive RT differed from the 463
      who did in that they had larger tumors and more frequently Grade 3 tumors. With a
      median follow-up of 3.6 years, in univariate analysis, RT was associated with
      improved disease-free survival (DFS) (relative risk 0.66; 95% confidence interval
      0.49-0.89; p = 0.007) and OS (relative risk 0.71; 95% confidence interval 0.50
      1.00; p = 0.051). In multivariate analysis, the relative risk for DFS and OS
      associated with RT was 0.78 and 0.94, respectively (p = not significant for
      both). Kaplan-Meier estimates showed better 5-year DFS (72% vs. 59%; p = 0.006)
      and OS (78% vs. 70%; p = 0.05) rates with RT. CONCLUSION: In the absence of
      detailed CT planning capacity, adjuvant RT for premenopausal Vietnamese women was
      associated statistically with short-term improvement in DFS and OS in univariate,
      but not multivariate, analysis.

PMID- 12788176
TI  - Initial clinical experience with moderate deep-inspiration breath hold using an
      active breathing control device in the treatment of patients with left-sided
      breast cancer using external beam radiation therapy.
AB  - INTRODUCTION: We present our initial clinical experience using moderate deep
      inspiration breath hold (mDIBH) with an active breathing control (ABC) device to
      reduce heart dose in the treatment of patients with early-stage, left-sided
      breast cancer using external beam radiation therapy (EBRT) limited to the whole
      breast. METHODS AND MATERIALS: Between February and August 2002, 5 patients with
      Stages I/II left-sided breast cancer received EBRT limited to the whole breast
      using an ABC device. After standard virtual simulation, patients with >2% of the
      heart receiving >30 Gy in free breathing were selected. All patients underwent a
      training session with the ABC apparatus to determine their ability to comfortably
      maintain mDIBH at 75% of the maximum inspiration capacity. Three patients
      received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4
      Gy in 28 fractions. For each of the medial and lateral tangential beams,
      radiation was delivered during 2 or 3 breath hold durations that ranged from 18
      to 26 s. "Step-and-shoot" intensity modulation was employed to achieve uniform
      dose distribution. Open beam segments were purposely delivered over 2 breath hold
      sessions and captured on electronic portal images to allow intra- and
      interfraction setup error analysis. All electronic portal images of the
      tangential beams were analyzed off-line using an in-house treatment verification
      tool to assess the anteroposterior, craniocaudal, and rotational uncertainties.
      Corrections were applied if necessary. RESULTS: A comparison of treatment plans
      performed on breath-hold and free-breathing CTs showed that ABC treatments
      achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart
      V(30)) and 1.5% in the heart normal tissue complication probability. A total of
      134 ABC treatment sessions were performed in the 5 patients. The average number
      of breath holds required per beam direction was 2.5 (4-6 per treatment) with a
      median duration of 22 s per breath hold (range: 10-26 s). Patients tolerated
      mDIBH well. The median treatment time was 18.2 min (range: 13-32 min), which was
      progressively shortened with increasing experience. A total of 509 portal images
      were analyzed. Combining measurements for all patients, the interfraction setup
      errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4
      mm, 3.2 mm, and 1 degrees, respectively, for the medial beam and 2.3 mm, 3.1 mm,
      and 1 degrees, respectively, for the lateral beam. For all patients, the
      intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD).
      CONCLUSION: Reduction in heart V(30) can be achieved in patients with left-sided
      breast cancer using mDIBH assisted with an ABC device. With increasing
      experience, ABC treatments were streamlined and could be performed within a 15
      min treatment slot. Our results suggest that mDIBH using an ABC device may
      provide one of the most promising methods of improving the efficacy of EBRT in
      patients with left-sided breast cancer, particularly when wide tangential beams
      are employed. Breast cancer; Breath hold; Radiation therapy; Intensity modulated
      radiation therapy

PMID- 12788177
TI  - Postmastectomy radiotherapy: patterns of recurrence and long-term disease control
      using electrons.
AB  - PURPOSE: To determine the patterns of failure and prognostic factors for
      locoregional recurrence after postmastectomy radiotherapy (RT), using a specific
      electron beam technique. METHODS AND MATERIALS: A uniform electron beam was used
      in 323 patients with invasive breast cancer at the University of Florida Health
      Science Center. The patterns of disease recurrence, prognostic factors, and
      overall outcome were studied. RESULTS: At 10 years, the freedom from locoregional
      recurrence, disease-free survival, and absolute survival rate was 90%, 62%, and
      55%, respectively. The 10-year disease-free survival rate for patients with 0, 1
      3, and >3 positive lymph nodes was 73%, 75%, and 47%, respectively. On
      multivariate analysis, the three factors significantly associated with
      locoregional recurrence were T stage, number of involved nodes, and RT fields.
      Full axillary fields appeared to be beneficial (p = 0.02). Patients with positive
      surgical margins appeared to benefit from a mastectomy incision boost to >/=65
      Gy. Finally, patients with T2N0 disease had a substantial risk of chest wall
      recurrence without chest wall RT. CONCLUSION: Findings include a low rate of
      clinically detectable locoregional recurrence. The data suggest benefits for the
      addition of full axillary RT in node-positive patients and chest wall RT in
      patients with T2N0 disease.

PMID- 12788178
TI  - Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive
      bladder cancer.
AB  - PURPOSE: To investigate the tolerance and efficacy of a modified concurrent
      chemoradiation (CCRT) protocol for patients with invasive bladder cancer "unfit"
      for radical cystectomy. METHODS AND MATERIALS: Twenty-three muscle-invasive
      bladder cancer patients who were unfit for or unwilling to receive radical
      cystectomy were enrolled in this study. All patients had transitional cell
      carcinoma of bladder, and distribution of stage was 14 (61%), 1 (4%), and 8 (35%)
      for T3a, T3b, and T4, respectively. This study included a relatively old-age
      population, with the median age being 75 and 70% of patients over 70 years old.
      Patients were treated with maximal transurethral resection of the bladder tumor
      followed by curative CCRT. The chemotherapy (C/T) regimen was comprised of
      cisplatin, 50 mg/m(2) intravenously (i.v.) on Day 1; 5-fluorouracil (5-FU), 500
      mg/m(2)/day by continuous i.v. infusion on Days 1-3; and leucovorin, 50 mg/day by
      continuous i.v. infusion on Days 1-3. Chemotherapy course was repeated at 21-day
      intervals. The radiation dose was 44-45 Gy to whole pelvis and 60-61.2 Gy to
      bladder, with a daily fraction of 1.8-2 Gy. The completeness of the CCRT protocol
      was defined as patients receiving at least 55 Gy of radiotherapy to the whole
      bladder and at least three courses C/T. RESULTS: Seventy-four percent of patients
      (17/23) completed the CCRT protocol. Radiation Therapy Oncology Group (RTOG)
      Grade 3 acute toxicities were observed in 4 patients, which included leucopenia,
      vomiting, genitourinary (GU) tract infection, and diarrhea. No treatment-related
      deaths occurred during the CCRT period. RTOG Grade 3 or more late complications
      were observed in 3 patients; one of them died of radiation cystitis superimposed
      with GU infection. Of the 18 patients whose response to CCRT was evaluated, a
      complete tumor response was documented in 16 patients (89%). With a median follow
      up of 3 years, the 3-year overall survival (OS) and disease-free survival (DFS)
      for all patients was 69% and 65% respectively. Meanwhile, the 3-year overall and
      DFS rates for patients who completed CCRT vs. those who did not complete CCRT
      were 82% vs. 33% and 75% vs. 33%, respectively (p = 0.18 for OS and p = 0.04 for
      DFS). CONCLUSIONS: Concurrent cisplatin, 5-FU, leucovorin, and radiotherapy for
      treatment of invasive bladder cancer is a feasible and promising treatment even
      for relatively old patients. Our results are comparable to those in recent
      studies by using combined modality treatment or neoadjuvant chemotherapy plus
      radical cystectomy. Consequently, this novel protocol warrants a prospective
      clinical trial and may be a safe, effective alternative to radical cystectomy.

PMID- 12788179
TI  - Accelerated superfractionated radiotherapy with concomitant boost for invasive
      bladder cancer.
AB  - PURPOSE: To determine the toxicity and clinical effectiveness of accelerated
      superfractionated radiotherapy with delayed concomitant boost (ASCBRT) in locally
      invasive carcinoma of the bladder. METHODS AND MATERIALS: Between July 1997 and
      December 2001, 87 patients (unsuitable or refusing cystectomy) with invasive
      bladder cancer underwent ASCBRT. The mean patient age was 66 years (range 40-90).
      The stage distribution was as follows: 2 T1, 51 T2, 13 T3, and 21 T4. Initially,
      the whole pelvis was treated by 1.8-Gy conventional daily fractions up to a total
      dose of 45 Gy. A small field boost covering gross disease was added as a second
      daily fraction (1.5 Gy) during the last 3 weeks of the 5-week schedule up to a
      total dose of 67.5 Gy. The interfraction interval was a minimum of 6 h. The
      patients were evaluated in follow-up for toxicity, local control, and survival.
      RESULTS: All but 2 patients completed the study protocol. Grade 3 acute urinary
      toxicity was observed in 2 patients. Grade 2 and 3 late bladder toxicity was
      observed in 12 patients and 1 patient, respectively. Grade 2 and 3 late bowel
      toxicity was observed in 5 and 3 patients, respectively. The 3-year actuarial
      local control, distant disease control, cause-specific survival, and overall
      survival rate was 64%, 78%, 58%, and 46%, respectively. Multivariate analysis
      revealed T stage as independent predictor of complete response. For Stage T2 and
      T3, the 3-year local control rate was 77% and 48%, respectively. At the last
      follow-up, 53 patients (61%) were still alive with a survival time between 6 and
      62 months. CONCLUSION: ASCBRT is feasible with acceptable tolerance even in
      relatively old patients with Stage T3 or greater tumor. The encouraging
      locoregional control and survival results of this institutional experience,
      favorable compared with conventional radical and other accelerated fractionated
      (with or without a concomitant boost) RT series, make ASCBRT worthy of further
      study in a Phase III trial.

PMID- 12788180
TI  - Appropriate radiation volume for stage IIA/B testicular seminoma.
AB  - PURPOSE: Prophylactic left supraclavicular fossa irradiation has been suggested
      to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma.
      To address this issue, we reviewed patterns of failure and treatment outcome in
      patients treated with radiation therapy at our institution. METHODS AND
      MATERIALS: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB,
      30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral
      (+/- contralateral) pelvic lymph nodes (dose: 25-35 Gy). RESULTS: With a median
      follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error:
      3%), and 2 patients have died of seminoma, giving a 5-year cause-specific
      survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left
      supraclavicular fossa. Five of 7 patients have been successfully salvaged.
      CONCLUSIONS: Prophylactic left supraclavicular fossa irradiation might have
      prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of
      patients would have received unnecessary left neck RT, so we continue to
      recommend, as standard treatment, infradiaphragmatic RT only.

PMID- 12788181
TI  - The prognostic significance of Gleason Grade in patients treated with permanent
      prostate brachytherapy.
AB  - PURPOSE: To assess the difference in biochemical freedom from relapse (BFR)
      between patients with clinically localized prostate cancer having Gleason Grade
      (GG) 3 + 4 vs. 4 + 3 disease treated with permanent prostate brachytherapy (PPB).
      METHODS AND MATERIALS: One thousand twenty-nine consecutive T1/T2 patients
      underwent PPB with Gleason sum 6, 7, or 8 adenocarcinoma of the prostate.
      Treatment consisted of transperineal ultrasound-guided implant as monotherapy or
      in combination with external beam radiation and/or neoadjuvant androgen ablation
      (NAAD). The Kattan modification of the ASTRO consensus definition that censors
      patients with rising follow-up PSA values early was used to measure BFR. Kaplan
      Meier actuarial survival was calculated and compared using the log-rank test. Cox
      proportional hazards regression was performed to assess the role of Gleason
      grade, initial PSA value, stage, the addition of external beam radiotherapy, and
      the addition of NAAD. RESULTS: The median follow-up for all 1029 patients is 46
      months (range: 3-108 months) with a BFR at 5 years of 78.2% and at 7 years of
      76.2%. The 7-year BFR for patients with GG 3 + 3 was 81.8%, GG 3 + 4 was 78.4%,
      GG 4 + 3 was 56.7%, and GG 4 + 4 was 50.7% (p < 0.0001). Cox regression analysis
      identified that the Gleason grade (p < 0.0001), initial PSA value (p = 0.001),
      D90% (p < 0.0001), and clinical stage (p = 0.016) were associated with
      biochemical recurrence, whereas NAAD (p = 0.057) and external beam radiotherapy
      (p = 0.356) were not. CONCLUSIONS: Gleason sum 7 tumors in patients treated with
      PPB represent a heterogeneous group of patients based on the differentiation of
      Gleason Grade 3 + 4 tumors vs. 4 + 3 disease. This information confirms similar
      conclusions identified in patients treated with external beam radiation and is
      useful when determining prognosis after PPB.

PMID- 12788182
TI  - Adjuvant and salvage radiotherapy after radical prostatectomy for prostate
      cancer.
AB  - PURPOSE: The optimal role of radiotherapy (RT) to the prostate bed after radical
      prostatectomy (RP) is the subject of much debate. In this study, the results of
      adjuvant RT (ART) and salvage RT (SRT) were compared. METHODS AND MATERIALS: A
      total of 146 lymph node-negative patients were treated postoperatively after RP
      with RT to the prostate bed between 1987 and 1998. Of these, 75 patients had an
      undetectable prostate-specific antigen (PSA) level and were treated with ART for
      adverse pathologic features only to a median dose of 60 Gy (range 51-70). A
      positive margin was identified in 96%, and two of the three with negative margins
      had seminal vesicle involvement (SVI). SRT was administered for either a
      persistently detectable PSA level after RP (n = 27) or for a delayed rise in PSA
      (n = 44) to a median dose of 70 Gy (range 60-78). Adjuvant androgen ablation was
      given to 37 patients; 2 who had received ART and 35 had who received SRT. The
      median duration of androgen ablation was 24 months. The primary end point was
      freedom from biochemical failure (bNED), which was considered to be an
      undetectable PSA level. The median follow-up was 53 months for all patients: 68
      months for the ART patients and 35 months for the SRT patients. RESULTS: For the
      ART group, 8 patients subsequently developed a rising PSA level. The 5-year bNED
      rate was 88%. SVI was the strongest predictor of outcome, with a 5-year bNED rate
      of 94% for those without SVI and 65% for those with SVI (p = 0.0002). SVI was the
      only significant factor in Cox proportional hazards regression analysis in the
      ART cohort. For the SRT group, 20 patients developed a rising PSA level after RT.
      The 5-year bNED rate was 66% for all SRT patients, and 43% and 78% in those with
      a persistently detectable PSA and those with a delayed rise in PSA, respectively.
      In the Cox proportional hazards regression analysis, this subdivision of SRT was
      statistically significant. Moreover, when the Cox model included all patients and
      variables, the timing of RT (ART vs. SRT) was an independent correlate of bNED,
      as was androgen ablation. CONCLUSION: For RP patients with high-risk pathologic
      features, the timing of postoperative RT and the PSA status after RP were strong
      determinants of outcome. Because of the potential confounding factors, direct
      comparisons of ART and SRT are problematic; however, ART is extremely effective
      and offers the surest approach for maintaining biochemical control.

PMID- 12788183
TI  - Radiation exposure to family and household members after prostate brachytherapy.
AB  - PURPOSE: Patients with localized prostate cancer frequently seek alternatives to
      radical surgery and external beam radiation therapy. Permanent prostate
      brachytherapy is an acceptable option. However, fears of radiation exposure to
      family members may deter some individuals from choosing this treatment option. A
      direct measurement was performed to determine the expected lifetime exposure from
      the patient with a brachytherapy prostate implant to family members and the
      household. METHODS AND MATERIALS: After a permanent brachytherapy implant with
      (125)I or (103)Pd, patients and their family members were provided radiation
      monitors to measure direct radiation exposure at home. Each patient was given two
      monitors to wear, and each member of the household, including the spouse,
      children, and pets, was given a single monitor. In addition, four rooms in the
      house frequently occupied by the patient were monitored. Based on the reading
      from the dosimeters measured at the first follow-up visit, the lifetime exposure
      to each individual or room was calculated. Forty-four patients, along with their
      families, agreed to participate and complied with the use of the dosimeters.
      Twenty-nine patients received a (125)I implant and 15 a (103)Pd implant. Assays
      were obtained on 272 monitors: 78 worn by patients, 52 worn by household members,
      and 142 posted in rooms. RESULTS: Exposures measured by patient dosimeters were
      within the expected range for the type of implant received. Exposures to family
      members were low. Based on dosimeter readings, the calculated mean lifetime dose
      to a spouse from her husband was 0.1 (range: 0.04-0.55) mSv for a (125)I implant
      and 0.02 (range: 0.015-0.074) mSv for a (103)Pd implant. Other family or
      household members had 0.07 (range: 0.04-0.32) mSv or 0.02 (range: 0.015-0.044)
      mSv for (125)I and (103)Pd implants, respectively. The calculated lifetime
      exposure did not exceed the annual limit set by the U.S. Nuclear Regulatory
      Commission in any of the cases. The majority of room dosimeters (94%) had no
      detectable radiation exposure. CONCLUSIONS: Radiation exposure to family members
      from a patient receiving a permanent prostate brachytherapy implant with
      radioactive (125)I or (103)Pd is very low and well below the limits recommended
      by the U.S. Nuclear Regulatory Commission. Radiation exposure to members of a
      patient's family or to the public should not be a deterrent to undergoing this
      procedure.

PMID- 12788184
TI  - Comparison of prognostic value of MRI and FIGO stage among patients with cervical
      carcinoma treated with radiotherapy.
AB  - PURPOSE: To compare the efficacy of MRI and FIGO stage, we performed
      retrospective multicenter analysis of patients with Stage II-III disease treated
      with radiation alone. METHODS AND MATERIALS: From three institutions, 164
      patients diagnosed with cervical carcinoma were entered into the study. The
      majority of this cohort received intracavitary brachytherapy combined with
      external beam radiotherapy (n = 161). Uni- and multivariate analyses were
      performed to identify the prognostic factors for overall survival (OAS), disease
      free survival (DFS), pelvic control (PC), and distant metastasis-free survival
      (DMFS). RESULTS: The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%,
      77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large
      tumor size/volume and positive lymph node enlargement (LN) showed a significantly
      unfavorable influence on survival and local and/or distant failure (p < 0.05).
      Using these two prognostic factors, patients were divided into three subgroups;
      the 5-year DFS rates of patients with risk 0 (volume </=50 cc and negative LN), 1
      (volume >50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%,
      53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume </=50 cc,
      disease stage proved to be a significantly prognostic factor of OAS, DFS, and PC
      (p < 0.05). However, these correlations were not observed in the large volume
      group (p > 0.05). CONCLUSION: MRI will provide more useful and practical
      information than will FIGO stage classification for patients with bulky disease,
      although this will remain a prognostic factor for patients with nonbulky disease
      (volume </=50 cc). With the aid of MRI, accurate and practical evaluation of
      clinical outcome could be achieved.

PMID- 12788186
TI  - Whole abdomen radiotherapy for patients with peritoneal dissemination of
      endometrial adenocarcinoma.
AB  - PURPOSE: No standard, universally accepted therapy exists for patients with
      adenocarcinoma of the endometrium with peritoneal dissemination. We report mature
      outcomes of selected patients with this uncommon pattern of spread treated with
      whole abdomen radiotherapy (RT). METHODS AND MATERIALS: A retrospective review
      was undertaken of all patients with a diagnosis of endometrial cancer referred to
      the Radiologic Associates of Sacramento Medical Group between January 1, 1988 and
      October 1, 1999. Eleven patients were identified who had surgically proven
      peritoneal dissemination (peritoneal seeding) treated with whole abdomen RT as
      the sole cytotoxic therapy after operative cytoreduction. Ten patients had
      International Federation of Obstetrics and Gynecology (1988) Stage IV disease at
      diagnosis, and one had peritoneal dissemination at the time of initial recurrence
      after hysterectomy for Stage I disease. RT was administered to the whole abdomen
      using 10-MV photons in fractions of 1.0 or 1.5 Gy. A cumulative dose of 30 Gy was
      given in all patients, with shielding used to reduce the dose to the liver and
      kidneys. Partial abdominal volumes (pelvis plus paraaortic nodes) received
      supplementary dose at 1.5-1.8 Gy/fraction to bring the cumulative dose within the
      limited volumes to 46.2-54 Gy. RESULTS: Four patients developed progressive
      cancer within 13 months of completion of whole abdomen RT. One additional patient
      died of hepatic venoocclusive disease (radiation hepatitis) 15 months after RT
      without evidence of cancer recurrence. Five patients were alive and clinically
      cancer free 55, 129, 131, 134, and 178 months after RT completion. One patient
      died of unrelated causes 79 months after treatment completion. CONCLUSION:
      Abdominal RT, in doses compatible with the acute and late tolerance of normal
      tissues, can eradicate small deposits of disseminated, intraperitoneal
      endometrial cancer. Currently, our patient selection criteria include limited
      peritoneal dissemination at diagnosis permitting complete surgical clearance (<1
      mm residual) of visible and palpable disease, Grade 1 or 2 histologic features,
      lack of demonstrable extraabdominal metastasis, and absence of major medical
      contraindications.

PMID- 12788185
TI  - Anemia in cervical cancers: impact on survival, patterns of relapse, and
      association with hypoxia and angiogenesis.
AB  - PURPOSE: The prognostic impact of anemia in cervical cancers is well established.
      We have investigated the impact of anemia on prognosis and patterns of relapse in
      cervical cancers. Furthermore, we analyzed the relationship between anemia, tumor
      hypoxia, and angiogenesis. METHODS AND MATERIALS: Eighty-seven patients (mean age
      58 years) with squamous cell cancer of the cervix (Stage IIB: n = 19; Stage IIIB:
      n = 59; Stage IVA: n = 9) were prospectively enrolled in the study from 1995
      through 1999. Patients underwent definitive radiotherapy with a combination of
      external beam radiotherapy (45-50.4 Gy) and high-dose-rate brachytherapy (5 x 7
      Gy). Tumor oxygenation was measured with the Eppendorf pO(2)-histograph before
      radiotherapy and after 19.8 Gy. Angiogenesis was determined by measuring the
      microvessel density in pretreatment biopsies in 46 patients. The impact of tumor
      oxygenation (at 0 Gy and 19.8 Gy), hemoglobin (hb) level (at 0 Gy and 19.8 Gy),
      angiogenesis and clinical parameters on survival and relapse was investigated.
      RESULTS: The 3-year overall survival rate (after a median follow-up of 42 months)
      was 57% for the whole group of patients, 72% for Stage IIB, 60% for Stage IIIB,
      and 22% for Stage IVA. The presence of pretreatment anemia had a significant
      impact on the relapse rate. However, the midtherapy hb level (at 19.8 Gy) had the
      strongest impact on local failure rate and survival: 3-year local failure rate
      was 6% in 20 patients with a hb > 13 g/dL at 19.8 Gy, 15% in 47 patients with an
      hb between 11 and 13 g/dL, and 67% in 20 patients with an hb < 11 g/dL, p =
      0.0001. This was associated with a significant impact on the 3-year overall
      survival, 79% vs. 64% vs. 32%. Twenty-three tumors were poorly oxygenated at both
      measurements (oxygen pressure [median pO(2)] < 15 mm Hg before therapy and at
      19.8 Gy). This group had a significantly lower 3-year overall survival as
      compared with patients with high pO(2) before and/or at 19.8 Gy (38% vs. 68%, p =
      0.02), and these poorly oxygenated tumors had also a significantly increased
      microvessel density. In a multivariate model, the midtherapy hb level maintained
      an overwhelming impact on local failure rate and survival. CONCLUSION: Hemoglobin
      level during radiotherapy was the strongest prognostic factor for local control
      and survival. We could further identify a poor prognostic subgroup with
      persisting hypoxia during radiotherapy, low hb levels, and increased
      angiogenesis. According to these findings, an association between anemia, poor
      tumor oxygenation, and angiogenesis is likely.

PMID- 12788187
TI  - Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation
      for patients with solitary and oligo brain metastasis using noninvasive fixation
      of the skull.
AB  - PURPOSE: To evaluate the efficacy and toxicity of hypofractionated stereotactic
      radiotherapy (HSRT) using noninvasive fixation of the skull on solitary or oligo
      brain metastatic patients as an alternative to stereotactic radiosurgery (SRS)
      using invasive fixation. PATIENTS AND METHODS: The subjects were 87 patients who
      had 4 or fewer brain metastases (50 solitary, 37 oligometastases). Treatment was
      conducted on 159 metastases by using a linac-based stereotactic system. The
      median isocentric dose was 35 Gy in 4 fractions. Whole-brain irradiation was not
      applied as an initial treatment. For the salvage treatment of metachronous brain
      metastases, repeat HSRT or whole-brain irradiation was applied. RESULTS: The
      actuarial 1-year local tumor control rate was 81%. Treatment-related
      complications were observed in 4 patients in the early period (<3 months) and in
      2 patients in the late period. The median survival period was 8.7 months.
      Metachronous brain metastases occurred in 30 patients, and none of the 18
      patients who were eligible for salvage HSRT refused to receive it again.
      CONCLUSIONS: Hypofractionated stereotactic radiotherapy achieved tumor control
      and survival equivalent to those of SRS reported in the literature. The results
      suggested that HSRT could be an alternative for solitary or oligo brain
      metastatic patients with less toxicity and less invasiveness compared to SRS.

PMID- 12788188
TI  - Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma.
AB  - PURPOSE: To evaluate tumor control and outcome from radiosurgery of meningiomas
      diagnosed by imaging without pathologic verification. METHODS AND MATERIALS: A
      total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife
      radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median
      treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28
      Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS:
      Tumor progression developed in 7 cases, 2 of which turned out to be different
      tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma).
      One tumor was controlled, but the development of other brain metastases suggested
      a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5
      and 10 years. The actuarial rate of identifying a diagnosis other than meningioma
      was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any
      postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No
      pretreatment variables correlated with tumor control in univariate or
      multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/-
      2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p =
      0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION:
      Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is
      associated with a high rate of tumor control and acceptable morbidity but carries
      a small risk (2.3%) of an incorrect diagnosis.

PMID- 12788189
TI  - Optic gliomas: a retrospective analysis of 50 cases.
AB  - PURPOSE: Gliomas of the optic pathways are rare childhood central nervous system
      tumors. The treatment approach is controversial because of its rarity and the
      slow and unpredictable growth rates of these lesions. METHODS AND MATERIALS: We
      reviewed 50 patients with the diagnosis of optic pathway low-grade gliomas
      treated between January 1980 and December 1995 at King Faisal Specialist Hospital
      and Research Center, Saudi Arabia. Thirty-five patients presented with
      chiasmatic/hypothalamic (posterior tumors), and 15 with optic nerve gliomas with
      or without chiasmal involvement (anterior tumors). Evidence of neurofibromatosis
      was present in 18 patients. Twenty-nine patients underwent surgery (total or
      partial resection), and 12 of these received postoperative radiotherapy (RT).
      Sixteen patients were treated with primary RT. The radiation dose varied between
      42 and 54 Gy (median dose 50). RESULTS: The overall actuarial survival rate was
      87.5% at 5 years and 75% at 10 years, and the corresponding progression-free
      survival (PFS) rates were 69% and 62%. Patients with anterior tumors fared better
      than those with posterior tumors, with a 10-year PFS rate of 72% and 58%,
      respectively; the difference, however, was not statistically significant (p =
      0.58). A PFS advantage was found in favor of patients with posterior tumors
      treated with RT (primary or postoperative) compared with no RT, with 5-year PFS
      rates of 68% vs. 42% (p = 0.03). This, however, did not translate into a survival
      advantage because of the success of salvage treatment. CONCLUSION: In
      multivariate analysis, age (<3 vs. >3 years) emerged as the only significant
      determinant for PFS with patients <3 years old faring worse (p = 0.03).
      Neurologic and endocrine dysfunction are significant problems that need to be
      addressed.

PMID- 12788190
TI  - Process and preliminary outcome of a patterns-of-care study of esophageal cancer
      in Japan: patients treated with surgery and radiotherapy.
AB  - PURPOSE: To evaluate the quality of radiotherapy (RT) in Japan, we have been
      carrying out a national survey through patterns-of-care studies (PCSs) since
      1996. We present the preliminary results of surgery combined with RT with or
      without chemotherapy for thoracic esophageal cancer. METHODS AND MATERIALS: A
      Japanese PCS data format for esophageal cancer was established based on one used
      in the United States and including information used in the surgical registration
      system in Japan, so that the results in both countries could be compared. An
      independent panel of radiation oncologists surveyed randomly selected
      institutions and patients between September 1998 and March 2001. There were 767
      esophageal cancer patients, of whom 220 had undergone preoperative or
      postoperative RT. RESULTS: The median age of the 220 patients was 62.3 years
      (range 31-89); of them, 88.1% were men. Pathologically, 218 patients (99.5%) had
      squamous cell carcinoma, predominantly located in the middle and lower thoracic
      esophagus, 41.7% of the patients had Stage III disease; they accounted for 52.6%
      of patients in nonacademic institutions and for 37.7% of those in academic
      institutions (p = 0.016). Sixty-nine patients received preoperative RT; of them,
      60.9% received chemotherapy; 145 patients received postoperative RT with or
      without chemotherapy. The spinal cord of 23 (11.7%) of 196 patients was
      irradiated with >/=50 Gy. In academic institutions, extended radical "three
      field" lymphatic dissection was performed for 72 (48.7%) of 148 patients;
      however, this sophisticated surgical procedure was done in only 13 (25.5%) of 51
      patients in nonacademic settings (p = 0.004). In all large academic institutions
      (those treating >/=300 patients annually), >/=6 MV of photon energy was used;
      30.5% of nonacademic institutes had linear accelerators of <6 MV photon (p =
      0.001). No deviations occurred in the radiation dose (median 46 Gy),
      fractionations, or fields between the two types of institutions. Univariate
      analyses showed that the statistically significant prognostic factors affecting
      overall survival were stage (p = 0.001), extended radical "three-field" lymphatic
      dissection (p = 0.001), no residual tumor (p = 0.001), supraclavicular RT (p =
      0.001), mediastinal RT (p = 0.025), Karnofsky performance status (p = 0.006)
      photon energy (p = 0.011), and stratification of the institutions (p = 0.001).
      Multivariate analysis showed that the type of institution (p = 0.045, risk ratio
      = 0.604), stage (p 0.029, risk ratio = 0.572), no residual tumor (p = 0.006, risk
      ratio = 0.487), photon energy (p = 0.043, risk ratio = 0.579), and use of
      chemotherapy (p = 0.012, risk ratio = 1.907) significantly affected overall
      survival. CONCLUSION: This PCS showed that in Japan important issues are present
      regarding RT for esophageal cancer that should be solved immediately, namely,
      treatment strategy, photon energy, and dose applied to the spinal cord. The PCS
      provided important information on how much improvement in structure and process
      would be required nationwide for RT of esophageal cancer.

PMID- 12788191
TI  - Contribution of conformal therapy in the treatment of anal canal carcinoma with
      combined chemotherapy and radiotherapy: results of a phase II study.
AB  - PURPOSE: To evaluate the feasibility of delivering conformal radiotherapy (RT)
      and concurrent chemotherapy without a mandatory break in patients with anal canal
      carcinoma. METHODS AND MATERIALS: Thirty patients with T2-T4 tumors were treated
      with a combination of 54 Gy in 30 fractions and two cycles of 5-fluorouracil and
      mitomycin C. Dose-volume histograms were obtained for bone marrow, small bowel,
      and skin to compare the conventional technique using the Radiation Therapy
      Oncology Group standard with our conformal technique. RESULTS: The mean dose
      ratio of the conventional compared with the conformal technique for bone marrow,
      small bowel, and skin was, respectively, 2.1-2.7, 3.0, and 2.0, in favor of the
      conformal technique. All patients completed their treatment without a treatment
      break. An incidence of Grade 3 toxicity for bone marrow, bowel, and skin of
      13.3%, 3.3%, and 20%, respectively, was observed. With a median follow-up of 33
      months, a 4-year local recurrence-free survival rate of 91% was observed.
      CONCLUSION: The results of this study have shown that conformal RT leads to a
      well-tolerated treatment. The treatment time is shortened to 6 weeks. A
      significant decrease in the acute toxicity rate suggests that by decreasing the
      "volume factor," conformal RT improves the therapeutic index in patients treated
      with combined chemotherapy and RT.

PMID- 12788192
TI  - Phase III quality-of-life study results: impact on patients' quality of life to
      reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.
AB  - PURPOSE: To determine whether prevention of hyposalivation after curative
      radiotherapy (RT) to the head and neck improves patients' quality of life (QOL).
      METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the
      volume of the major salivary glands, provide unstimulated and stimulated saliva
      samples, and complete the University of Washington head-and-neck QOL tool before
      RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5
      mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between
      March 1998 and January 2000. Of these, 214 were eligible for QOL analysis.
      Patients were evenly distributed between arms by race, gender, tobacco use, tumor
      site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status
      of 90% was more common in the pilocarpine arm. Twenty percent of the patients on
      the pilocarpine arm and 29% of the patients on the placebo arm were taking
      nutritional supplements. The placebo arm patients had greater mouth pain and
      chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and
      50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049,
      respectively) preservation of salivary function in the pilocarpine arm, patients
      on the pilocarpine arm reported difficulties with swallowing (75%), activity
      (80%), hyposalivation (64%), and taste (81%). No difference was noted between
      arms at 3 months in mucositis scores, with both arms demonstrating increased
      requirement for oral nutrients. CONCLUSION: Objective prevention of
      hyposalivation did not affect patients' assessment of salivary function or QOL
      because of the greater impact mucositis plays in QOL after RT.

PMID- 12788193
TI  - Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer:
      correlation with outcome of patients after radiotherapy.
AB  - PURPOSE: The expression of inducible nitric oxide synthase (iNOS) and bcl-2
      proteins was evaluated and the prognostic significance determined in
      nasopharyngeal cancer (NPC) patients treated by radiotherapy. METHODS AND
      MATERIALS: Tissue sections from 55 patients with NPC were assessed for iNOS and
      bcl-2 protein expression by immunohistochemistry, immunoelectron microscopy, and
      in situ hybridization before treatment. The markers were correlated with
      apoptosis (detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling assay) and clinicopathologic parameters. RESULTS: All NPC
      sections exhibited positive iNOS and bcl-2 immunoreactivity, with a mean
      percentage of 6.24% +/- 0.58% and 17.09% +/- 2.48%, respectively. A significant
      positive correlation was observed between iNOS expression and the apoptotic index
      (p < 0.0001, Pearson's r = 0.8518), and bcl-2 expression correlated inversely
      with apoptosis (p = 0.0001; Pearson's r = -0.6170). A significant inverse
      correlation was found between iNOS and bcl-2 immunoreactivity (p < 0.0001,
      Pearson's r = -0.7144). Bcl-2 but not iNOS expression was associated with the
      stage of the tumor according to the criteria of the American Joint Committee on
      Cancer (1997) (p < 0.0001). Patients who had recurrence of the tumor and
      metastasis after radiotherapy had a lower expression of iNOS (p = 0.014 and p =
      0.035, respectively), although overall survival was not significantly different
      statistically. Higher bcl-2 expression was also associated with local tumor
      recurrence (p = 0.005) but not with metastasis or overall survival. CONCLUSION:
      It appears that iNOS and bcl-2 expression may be potentially useful biomarkers
      for predicting the outcome of radiotherapy in NPC patients.

PMID- 12788194
TI  - Radiation sensitization of human cancer cells in vivo by inhibiting the activity
      of PI3K using LY294002.
AB  - Multiple genetic alterations such as in Ras or EGFR can result in sustained
      signaling through PI3K. Our previous experiments have shown that resistance to
      radiation results from PI3K activity in cells in culture. Here we examined
      whether inhibition of PI3K in vivo would sensitize tumors to radiation. The human
      bladder cancer cell line T24 has amplified and mutated H-Ras resulting in
      sustained PI3K activity and phosphorylation of the downstream target of PI3K,
      Akt. Nude mice bearing T24 tumor cell xenografts were randomly assigned to one of
      four groups: control, radiation alone, the PI3K inhibitor LY294002 alone, or
      combined LY294002 and radiation. The LY294002 was delivered intraperitoneally to
      the mice. Downregulation of Akt was documented by Western blot analysis of tumor
      lysates. In vivo sensitization was measured using clonogenic assays or regrowth
      assays.A dose of 100 mg/kg of LY294002, but not 50 mg/kg, consistently eliminated
      the phosphorylation of Akt. This inhibition was transient, and Akt activity
      returned after 30 min. This dose resulted in severe respiratory depression and
      lethargy resolving without lethality. It is not possible to tell whether these
      side effects of LY294002 were mechanism-based or idiosyncratic. The PI3K
      inhibitor LY294002 by itself had minimal antitumor effect. The combination of
      LY294002 and radiation resulted in significant and synergistic reduction in
      clonogenicity and growth delay. Inhibition of PI3K by LY294002 can
      synergistically enhance radiation efficacy. This acts as a proof of principle
      that inhibition of the Ras to PI3K pathway could be useful clinically.

PMID- 12788195
TI  - Intraoperative dynamic dose optimization in permanent prostate implants.
AB  - PURPOSE: With the advent of intraoperative optimized planning, the treatment of
      prostate cancer with permanent implants has reached an unprecedented level of
      dose conformity. However, because of well-documented (and unavoidable)
      inaccuracies in seed placement into the gland, carrying out a plan results in a
      large degree of variability relative to the intended dose distribution. This
      brings forth the need to periodically readjust the plan to allow for the real
      positions of seeds already implanted. In this paper, an algorithm for performing
      this task, hereby described as intraoperative dynamic dose optimization (IDDO),
      is presented and assessed. METHODS AND MATERIALS: The general scheme for
      performing IDDO consists of three steps: (1) at some point during the implant,
      coordinates of implanted seeds are identified; (2) seed images are projected onto
      the reference frame of the ultrasound images for planning; and (3) the plan is
      reoptimized. Work on the first two steps is reported elsewhere. Here, we focus on
      the strategy for implementing the reoptimization step. An optimal treatment plan
      is first obtained based on initial operating room-acquired ultrasound images. We
      analyze the sensitivity and effect of the IDDO procedure with respect to the
      total number of reoptimizations performed. Specifically, we consider reoptimizing
      2, 3, and 4 times. When two reoptimizations are used, half of the seeds from the
      initial optimal plan are implanted. The first reoptimization is performed on the
      remaining possible seed positions, and all the seeds designated in this
      reoptimized plan are implanted. The second (final) reoptimization is done on the
      remaining unused seed positions to ensure 100% coverage of the gland and to
      eliminate possible cold spots in the gland. Similarly, when three reoptimization
      steps are used, one-third of the seeds from the initial optimized plan, one-half
      of the seeds from the first reoptimization, and all seeds from the second
      reoptimization are implanted. The third (final) reoptimization is performed to
      assist in eliminating possible cold spots. Reoptimizing four times proceeds in a
      like manner. Fifteen patient cases are used for comparison. Strict dose bounds of
      100% and 120% of the prescription dose are imposed on the urethra, and 100%
      coverage is imposed on the prostate volume. To assist in achieving good
      conformity, prostate contour points are assigned a target upper dose bound of
      150% of the prescription dose. RESULTS: A two-way comparison is performed: (a)
      initial optimized plan, (b) IDDO plan. Postimplant dose analysis, coverage and
      conformity measures, as well as actual dose received by urethra and rectum are
      used to gauge the results. The initial optimized plan consistently provides 93%
      prescription dose coverage to the gland with average conformity index of 1.32.
      The urethra dose ranges within 100% to 150%, and the maximum dose delivered to
      the rectum reaches 91% of the prescription dose. On average, about 50% of the
      urethra receives more than 120% of the prescription dose, and 19% of the rectum
      volume receives more than the 78% upper dose limit. For the IDDO plan, 100%
      postimplant coverage with 1.16 conformity is achieved. Urethra and rectum dose is
      maintained within the prescribed 100% to 120% range and 78% upper bound,
      respectively. CONCLUSIONS: With real-time treatment planning, it is possible to
      dynamically reoptimize treatment plans to account for actual seed positions (as
      opposed to planned positions) and needle-induced swelling to the gland during
      implantation. Postimplant analysis shows that the final seed configuration
      resulting from the IDDO method yields improved dosimetry. The algorithmic design
      ensures that one can achieve complete coverage while maintaining good conformity,
      thus sparing excess radiation to external tissue. The study also provides
      evidence of the possibility of morbidity reduction to urethra and rectum (because
      of reduced dose delivered to these structures) via the use of IDDO planning.
      Clinical studies are needed to validate the importance of our approach.

PMID- 12788197
TI  - Patient-specific point dose measurement for IMRT monitor unit verification.
AB  - PURPOSE: To review intensity-modulated radiation therapy (IMRT) monitor unit
      verification in a phantom for 751 clinical cases. METHODS AND MATERIALS: A custom
      water-filled phantom was used to measure the integral dose with an ion chamber
      for patient-specific quality assurance. The Corvus IMRT planning system was used
      for all cases reviewed. The 751 clinical cases were classified into 9 treatment
      sites: central nervous system (27 cases), gastrointestinal (24 cases),
      genitourinary (447 cases), gynecologic (18 cases), head and neck (200 cases),
      hematology (12 cases), pediatric (3 cases), sarcoma (8 cases), and thoracic (12
      cases). Between December 1998 and January 2002, 1591 measurements were made for
      these 751 IMRT quality assurance plans. RESULTS: The mean difference (MD) in
      percent between the measurements and the calculations was +0.37% (with the
      measurement being slightly higher). The standard deviation (SD) was 1.7%, and the
      range of error was from -4.5% to 9.5%. The MD and SD were +0.49% and 1.4% for
      MIMiC treatments delivered in 2-cm mode (261 cases) and -0.33% and 2.7% for those
      delivered in 1-cm mode (36 cases). Most treatments (420) were delivered using the
      step-and-shoot multileaf collimator with a 6-MV photon beam; the MD and SD were
      +0.31% and 1.8%, respectively. Among the 9 treatment sites, the prostate IMRT (in
      genitourinary site) was most consistent with the smallest SD (1.5%). There were
      23 cases (3.1% of all cases) in which the measurement difference was greater than
      3.5%; of those, 6 cases used the MIMiC in 1-cm mode, and 14 of the cases were
      from the head-and-neck treatment site. CONCLUSION: IMRT monitor unit calculations
      from the Corvus planning system agreed within 3.5% with the point-dose ion
      chamber measurement in 97% of 751 cases representing 9 different treatment sites.
      A good consistency was observed across sites.

PMID- 12788196
TI  - (Non)-migration of radiopaque markers used for on-line localization of the
      prostate with an electronic portal imaging device.
AB  - PURPOSE: Radiopaque gold markers can be implanted in the prostate to visualize
      its position on portal images during radiation therapy. This procedure assumes
      that the markers do not move within the prostate. In this work we test this
      assumptiom. METHODS AND MATERIALS: Three markers were implanted transrectally in
      the prostate of patients undergoing external radiation therapy. An orthogonal
      pair of portal images was acquired periodically throughout the course of
      radiation therapy with an a-Si electronic portal imaging device (EPID). The
      marker coordinates were determined, and the distances between the implanted
      markers were recorded. The distance time trend is used to evaluate the magnitude
      of marker migration. RESULTS: The average standard deviation (SD) of the
      distances between markers was 1.3 mm (range 0.44 to 3.04 mm). Three of the 11
      patients show a SD larger than 2 mm. For these patients, all three distances show
      a simultaneous reduction with time, compatible with a shrinking of the prostate.
      All had been treated with neoadjuvant hormone therapy. For 1 of the 3 patients,
      this reduction in volume was confirmed with a repeat computed tomographic scan.
      CONCLUSION: None of the 33 markers studied migrated significantly. The
      implantation of three radiopaque gold markers enables accurate and precise on
      line verification of the prostate position during external beam radiation
      therapy. The use of three markers provides a tool to monitor prostate position
      and volume changes that can occur over time due to hormone or radiation therapy.

PMID- 12788198
TI  - Automated beam angle and weight selection in radiotherapy treatment planning
      applied to pancreas tumors.
AB  - PURPOSE: To extend and investigate the clinical value of a recently developed
      algorithm for automatic beam angle and beam weight selection, for irradiation of
      pancreas tumors. METHODS AND MATERIALS: The algorithm aims at generation of
      acceptable treatment plans, i.e., delivering the prescribed tumor dose while
      strictly obeying the imposed hard constraints for organs at risk and target.
      Extensions were made to minimize the beam number and/or to escalate the tumor
      dose. For 5 pancreas patients, the clinical value and the potential for beam
      number reduction and dose escalation were investigated. Comparisons were made
      with clinical plans and equiangular plans. RESULTS: Compared to clinical plans,
      the generated plans with the same number of beams yielded a substantial reduction
      in the dose to critical tissues. Using the algorithm, an escalated tumor dose of
      58 Gy could be achieved for two cases. Maximum dose escalations required a
      minimum of 3 to 4 beam orientations. For 13 CT slices and an in-slice resolution
      of 0.5 cm, the total calculation times were 23-55 min, including precalculation
      of 180 input dose distributions (15 min). CONCLUSIONS: The algorithm yielded
      acceptable treatment plans with clinically feasible numbers of beams, even for
      escalated tumor doses. Generated plans were superior to the clinically applied
      plans and to equiangular setups. Calculation times were clinically acceptable.
      The algorithm is now increasingly used in clinical routine.

PMID- 12788199
TI  - A reanalysis of the Collaborative Ocular Melanoma Study Medium Tumor Trial eye
      plaque dosimetry.
AB  - PURPOSE: To recalculate the radiation doses delivered to structures of interest
      within the eye, i.e., the lens, tumor apex, 5-mm point, optic disk, and macula
      for patients treated with eye plaque radiotherapy on the Collaborative Ocular
      Melanoma Study (COMS) Medium Tumor Trial, using updated dosimetric data. METHODS
      AND MATERIALS: Using the Plaque Simulator planning system, doses were
      recalculated for a sampling of COMS patients for each plaque size. Dosimetry
      parameters incorporated into the recalculation were line source approximation, a
      90% Silastic transmission factor, and a 0% gold transmission factor. Generic
      solutions were generated from the dose recalculations for each plaque size and
      structures of interest combination. Doses for the remainder of the patient
      population were recalculated using the generic solutions and compared with the
      originally reported COMS doses. RESULTS: Doses to all structures of interest were
      reduced 7%-21%, depending on the plaque size and structure combination. The
      reduction in dose for the macula, optic disc, lens, tumor apex, and 5-mm point
      was on average 10%, 18%, 8%, 11%, and 12%, respectively. The closer the macula
      and optic disk were to the plaque rim, the greater the dose reduction.
      Incorporation of the Silastic transmission factor accounted for a large part of
      the dose reduction. CONCLUSIONS: Incorporating anisotropy, line source
      approximation, and Silastic and gold shield attenuation into dose recalculations
      resulted in a significant and consistent reduction of doses to structures of
      interest within the eyes.

PMID- 12788200
TI  - In vivo alanine/EPR dosimetry in daily clinical practice: a feasibility study.
AB  - PURPOSE: The objective of this study was evaluation of accuracy of in vivo
      dosimetry using electron paramagnetic resonance (EPR) in alanine. Additionally,
      we aimed to identify sources of uncertainty in dose determination and
      quantitative assessment of physical factors that may result in discrepancies
      between the measured and planned single-fraction doses. METHODS AND MATERIALS:
      The measurements were performed using detectors in a form of 1.6 cm x 1.6 cm
      polyethylene sachets filled with powdered L-alanine. The detectors were taped to
      the patient's skin and measured the entrance doses for (60)Co and electron beams.
      Some detectors were covered with buildup material, and some measured the "skin
      dose." The EPR measurements were performed with a Varian E-4 spectrometer.
      RESULTS: The calculated uncertainty of EPR measured doses was dependent on
      measured doses and varied from 6.6% for 0.5 Gy to 3.2% for 2 Gy. The calculated
      uncertainty was in concordance with experimentally determined reproducibility of
      EPR signals. However, the deviations between measured and planned doses exceeded
      the uncertainty range of EPR measurements, which can be attributed to uncertainty
      in determination of actually delivered doses to the detectors, on the basis of
      treatment planning data. CONCLUSION: The accuracy of dose determination by EPR
      measurements was shown to be achievable within the 5% limit recommended by the
      ICRU for doses above 0.7 Gy. The accuracy of in vivo verification of radiotherapy
      doses by in vivo EPR dosimetry can be improved by meticulous selection of
      measurement conditions, i.e., radiation fields and detector positions, ensuring
      accurate calculation of doses delivered to the dosimeters.

PMID- 12788201
TI  - Comparison of MRI pulse sequences in defining prostate volume after permanent
      implantation: in regard to McLaughlin et al., IJROBP 2002;54:703-711.

PMID- 12788203
TI  - Radiotherapy for benign familial pemphigus.

PMID- 12788204
TI  - Causative and susceptibility genes for Alzheimer's disease: a review.
AB  - Alzheimer's disease (AD) is the most common type of dementia in the elderly
      population. Three genes have been identified as responsible for the rare early
      onset familial form of the disease: the amyloid precursor protein (APP) gene, the
      presenilin 1 (PSEN1) gene and the presenilin 2 (PSEN2) gene. Mutations in these
      genes, however, account for less than 5% of the total number of AD cases. The
      remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex
      aetiology due to interactions between environmental conditions and genetic
      features of the individual. In this paper, we review the most important genes
      supposed to be involved in the pathogenesis of AD, known as susceptibility genes,
      in an attempt to provide a comprehensive picture of what is known about the
      genetic mechanisms underlying the onset and progression of AD. Hypotheses about
      the role of each gene in the pathogenic pathway are discussed, taking into
      account the functions and molecular features, if known, of the coded protein. A
      major susceptibility gene, the apolipoprotein E (APOE) gene, found to be
      associated with sporadic late-onset AD cases and the only one, whose role in AD
      has been confirmed in numerous studies, will be included in a specific chapter.
      As the results reported by association studies are conflicting, we conclude that
      a better understanding of the complex aetiology that underlies AD may be achieved
      likely through a multidisciplinary approach that combines clinical and
      neurophysiological characterization of AD subtypes and in vivo functional brain
      imaging studies with molecular investigations of genetic components.

PMID- 12788205
TI  - Representations of motivational drives in mesial cortex, medial thalamus,
      hypothalamus and midbrain.
AB  - We propose that neural representations of motivational drives, including sexual
      desire, hunger, thirst, fear, power-dominance, the motivational aspect of pain,
      the need for sleep, and nurturance, are represented in four areas in the brain.
      These are located in the medial hypothalamic/preoptic area, the periaqueductal
      gray matter (PAG) in the midbrain/pons, the midline and intralaminar thalamic
      nuclei, and in the anterior part of the mesial cortex, including the medial
      prefrontal and anterior cingulate areas. We attempt to determine the locations of
      each of these representations within the hypothalamus/preoptic area,
      periaqueductal gray and cortex, based on the available literature on activation
      of brain structures by stimuli that evoke these forms of motivation, on the
      effects of electrical and chemical stimulation and lesions of candidate
      structures, and on hodological data. We discuss the hierarchical organization of
      the representations for a given drive, outputs from these representations to
      premotor structures in the medulla, caudate-putamen, and cortex, and their
      contributions to involuntary, learned-sequential (operant) and voluntary
      behaviors.

PMID- 12788206
TI  - Frontal activation during a verbal-fluency task as measured by near-infrared
      spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) is an optical method which allows non-invasive
      in vivo measurements of concentration changes of oxygenated hemoglobin (O(2)Hb)
      and deoxygenated hemoglobin (HHb) in brain tissue. The present study investigated
      the blood oxygenation changes that were associated with the execution of the
      Verbal-Fluency Test (VFT) in left and right prefrontal brain areas of 14 healthy
      subjects by means of NIRS. During the VFT, subjects were required to pronounce as
      many nouns as possible beginning with the letters "A," "F," and "S." Compared to
      a baseline resting condition, we found a significant increase of O2Hb (left
      hemisphere: baseline, 1.2+/-1.1microm; VFT(letterS), 3.56+/-2.02microm; right
      hemisphere: baseline, 1.26+/-1.08microm; VFT(letterS), 3.67+/-2.03microm) and a
      significant decrease of HHb (left hemisphere: baseline, -0.21+/-0.59microm;
      VFT(letterS), -0.67+/-0.60microm; right hemisphere: baseline, -0.29+/-0.53microm;
      VFT(letterS), -0.68+/-0.44microm) during the execution of the VFT over both
      hemispheres. No lateralization effects were observed. The results confirm that
      NIRS is suitable for the measurement of blood oxygenation changes in frontal
      brain areas that are associated with cognitive tasks.

PMID- 12788207
TI  - Ectopic serotonin accumulation and efflux in rat mesencephalic slices after prior
      tissue 'radiolabelling'.
AB  - Radiolabelling of brain tissue has long been used to facilitate detection of
      transmitter efflux, on the assumption that egress of tritiated monoamines
      reflects that of the endogenous transmitter. The present study tested the
      hypothesis that the application of exogenous serotonin (5-HT) to mesencephalic
      slices, in the manner used during a typical radiolabelling protocol, leads to
      efflux of 5-HT from physiologically inappropriate loci such as other non
      serotonergic neurones. We used fast cyclic voltammetry (FCV) to determine the
      effect of tissue pre-incubation with 5-HT on electrically-stimulated 5-HT efflux
      and reuptake in rat mesencephalic slices. Seven subregions were studied,
      including the dorsal raphe nucleus (DRN), dorsomedial periaqueductal grey (PAGdm)
      and the oral part of the pontine reticular nucleus (PnO). In control slices (pre
      incubated without 5-HT), stimulated 5-HT efflux was only detectable in DRN, PAGdm
      and occasionally in PnO. In slices incubated in 5-HT (100nM) for 30min,
      stimulated 5-HT efflux was detected in all seven subregions studied. In such
      slices, citalopram (75nM) increased efflux and reuptake t(1/2) in DRN to 201+/-21
      and 487+/-117% of pre-drug values (P<0.05) but had no significant effect on
      either measure in PnO. The 5-HT1 autoreceptor agonist, 5-carboxamidotryptamine (5
      CT, 100nM) decreased efflux in DRN by 54+/-6% (P<0.05), but was without effect
      (10+/-14%) in PnO. The present results show that pre-incubation in 5-HT allows
      stimulated 5-HT efflux from regions of the mesencephalon other than DRN and
      PAGdm. This stimulated 5-HT efflux is apparently not influenced by 5-HT
      transporters or 5-HT1 autoreceptors, suggesting that efflux is ectopic, an
      artefact of the pre-incubation process. In summary, incubation of rat
      mesencephalic tissue in 5-HT, in the manner of a typical radiolabelling protocol,
      results in stimulated 5-HT efflux from non-physiological sites. The results of
      such transmitter efflux studies should thus be interpreted with caution.

PMID- 12788208
TI  - Fos induction in the rat deep cerebellar and vestibular nuclei following central
      administration of colchicine: a qualitative and quantitative time-course study.
AB  - The present study was conducted to demonstrate Fos expression at four levels
      (anterior, prefastigial, postfastigial, posterior) of the cerebellar-vestibular
      nuclear complex in rats exposed to 1, 6, 24, and 48h of colchicine treatment
      using a light microscopic avidin biotin peroxidase (ABC) immunohistochemistry.
      Intracerebroventricular administration of colchicine (60microg per 10microl
      saline) elicited a continuous increase in the number of Fos-positive cells in the
      main cerebellar (fastigial, interpositus, dentatus) and vestibular (superior,
      medial, lateral, spinal, Y) nuclei. One and six hours after colchicine treatment,
      intensive Fos labeling was observed only in the pyriform cortex and the
      hypothalamic paraventricular nucleus, respectively, and there was no Fos
      immunolabeling in any of the cerebellar or vestibular structures investigated. On
      the other hand, moderate number of Fos-positive cells was visible in each of the
      cerebellar and vestibular nuclei 24h after colchicine treatment. Exposure of the
      animals to 48h of colchicine treatment induced an additional, more than 50%, rise
      in the accumulation of Fos-positive profiles in almost all the cerebellar and
      vestibular nuclei. In addition, at this time-point, a characteristic pattern of
      Fos distribution appeared almost in all of the cerebellar and vestibular nuclei,
      however, the numerical incidence of Fos-positive profiles in paired structures
      along the neuroaxis was bilaterally symmetric. The present data demonstrate for
      the first time that the central administration of colchicine causes a persistent
      and, in comparison with other brain areas, time-delayed activation of certain
      population of neurons in both cerebellar and vestibular nuclei. We assume that
      the delayed Fos activation in these structures indicate that the cerebellar and
      vestibular nuclei are not the primary targets of the central effect of colchicine
      and their activation seems to be rather a result of a postponed functional
      consequences of the central action of colchicine probably related to the
      coordination of motor performance.

PMID- 12788209
TI  - Coeruleotrigeminal suppression of nociceptive sensorimotor function during
      inflammation in the craniofacial region of the rat.
AB  - Descending action from the locus coeruleus (LC) on the trigeminal sensorimotor
      function was evaluated in a rat model of oral-facial inflammation. For the
      induction of oral-facial inflammation, mustard oil (20% solution in 20microl
      mineral oil) was injected into the region of the temporomandibular joint (TMJ).
      One week before testing, rats received bilateral lesions of the LC using a
      cathodal current. The electromyogram (EMG) threshold, which is the threshold
      intensity for the onset of EMG activity of the masseter muscle evoked by pressure
      on the TMJ region, was used in the present study as an indicator of the
      trigeminal sensorimotor function. Following mustard oil injection, in the LC
      lesioned rats, EMG thresholds significantly decreased at 30min, which lasted up
      to 240min. In contrast, EMG thresholds in the LC-intact rats returned to the
      level before injection after 180min. Systemic naloxone (1.3mg/kg, i.v.) produced
      a further decrease of EMG thresholds in both the LC-intact and LC-lesioned rats.
      Under the existence of naloxone, EMG thresholds in the LC-lesioned rats were
      significantly lower than those of the LC-intact rats. These results suggest that
      oral-facial inflammation activates the coeruleotrigeminal modulating system and
      that an action of this system is independent of the opioid depressive mechanism.

PMID- 12788210
TI  - Effect of cold face stimulation on cerebral blood flow in humans.
AB  - BACKGROUND AND PURPOSE: In humans, activation of the diving reflex by a cold
      stimulus to the face results in bradycardia, peripheral vasoconstriction and an
      increase in blood pressure. However, responses of the cerebral blood flow have
      not yet been evaluated. We undertook this study to assess the effect of cold face
      stimulation on the cerebral circulation in humans. METHODS: Seventeen healthy
      volunteers, aged 27+/-5 years were evaluated during application of a cold
      stimulus (0 degrees C) to the forehead for 60s. We continuously monitored mean
      arterial pressure (MAP), mean flow velocity (MFV) of the middle cerebral artery,
      cardiac output, skin blood flow, heart rate and end-tidal CO2. Total peripheral
      resistance (TPR) was calculated as MAP divided by cardiac output. Cerebrovascular
      resistance index (CVRi) was calculated as MAP divided by MFV. RESULTS: Cold face
      stimulation did not significantly affect cardiac output but resulted in
      significant decreases in heart rate and skin blood flow and an increase in MAP.
      MFV in the mid-cerebral artery showed a slight, but significant increase. The
      maximum increase in CVRi (14.2+/-11.4%) was significantly (P<0.01) less than the
      maximum increase in TPR (23.9+/-5.7%). End-tidal CO2 did not change significantly
      during the cold stimulation. CONCLUSIONS: In contrast to other sympathetic
      stimulations (e.g. lower body negative pressure), facial cooling results in an
      increase in cerebral blood flow. The amount of cerebral vasoconstriction was less
      than the amount of total peripheral vasoconstriction. These results suggest that
      although there is some constriction of the cerebral resistance vessels during
      cold face stimulation, cerebral perfusion was maintained, possibly by opposing
      parasympathetic activation.

PMID- 12788211
TI  - Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial
      reversibility after continuous positive airway pressure (CPAP).
AB  - The aims of this study were to assess cognitive function in obstructive sleep
      apnea (OSA) patients and to evaluate the effect of short- and long-term treatment
      with continuous positive airway pressure treatment (CPAP). A battery of
      neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck
      Inventory Scale were administered to 23 patients with severe OSA (age: 56.5+/
      6.13; AHI: 54.9+/-13.37) and to 23 age- and education-matched controls. The OSA
      patients were evaluated in a baseline condition and in two follow-up treatment
      sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA
      patients had a significant impairment, compared to controls, in tests of
      sustained attention, visuospatial learning, executive function, motor
      performance, and constructional abilities. The longitudinal evaluation showed
      that after a 15-days CPAP treatment attentive, visuospatial learning, and motor
      performances returned to normal levels. A 4-months CPAP treatment did not result
      in any further improvement in cognitive tests. Performance on tests evaluating
      executive functions and constructional abilities was not affected by short- and
      long-term treatment with CPAP. The findings of this study confirm the hypothesis
      of partial reversibility of cognitive dysfunction in OSA patients after CPAP.

PMID- 12788212
TI  - Development of antinociceptive tolerance and changes of opioid receptor ligand
      binding in central nervous system of the mouse forced to single and repeated
      swimming in the cold water.
AB  - The present study was designed to characterize underlying mechanism involved in
      the development of tolerance in the production of antinociceptive effect induced
      by repeated cold water swimming stress (CWSS) using the tail-flick test. Mice
      were forced to swim at 4 degrees C for 3min and the tail-flick test was performed
      5, 10, 20, and 30min after the swimming. The profound antinociception was induced
      by a single CWSS. However, when the mice were exposed to CWSS repeatedly seven
      times, they showed a tolerance in the production of antinociception. In the
      opioid receptor binding study, Bmax of delta opioid receptor (DOR) was decreased
      in the brainstem, midbrain and the spinal cord areas by both a single and
      repeated CWSS, without altering Kd value. However, Bmax values of mu opioid
      receptor (MOR) and kappa opioid receptor (KOR) were increased in the brainstem,
      midbrain and spinal cord regions by repeated CWSS, without changing Kd values.
      Our results suggest that the development of tolerance in the production of
      antinociception in mice forced to the repeated CWSS may be, at least, due to the
      reduction of DOR number in the brainstem, midbrain and the spinal cord regions.

PMID- 12788213
TI  - Cycloheximide inhibits neurotoxic responses induced by kainic acid in mice.
AB  - In the present study, we examined the effect of cycloheximide on various
      pharmacological responses induced by kainic acid (KA) administered
      intracerebroventricularly (i.c.v.) in mice. In a passive avoidance test, a 20-min
      cycloheximide (200mg/kg, i.p.) pretreatment prevented the memory impairment
      induced by KA. The morphological damage induced by KA (0.1microg) in the
      hippocampus was markedly concentrated in the CA3 pyramidal neurons and
      cycloheximide effectively prevented the KA-induced pyramidal cell death in CA3
      hippocampal region. In immunohistochemical study, KA dramatically increased the
      phosphorylation of extracellular signal-regulated protein kinase (p-ERK), c-Jun N
      terminal kinase 1 (p-JNK1), and calcium/calmodulin-dependent protein kinase II (p
      CaMK II). Cycloheximide attenuated the increased p-ERK, p-JNK1, and p-CaMK II
      levels induced by KA. Furthermore, cycloheximide inhibited the increased c-Fos
      and c-Jun protein expression levels induced by KA in the hippocampus. The
      activation of microglia was detected in KA-induced CA3 cell death region by
      immunostaining with a monoclonal antibody against the OX-42. Cycloheximide
      inhibited KA-induced increase of OX-42 immunoreactivity. Our results suggest that
      the increased expression of the c-Fos, c-Jun, and phosphorylation of ERK, JNK1,
      and CaMK II proteins may play important roles in the memory impairment and the
      cell death in CA3 region of the hippocampus induced by i.c.v. KA administration
      in mice. Furthermore, the activated microglia may be related to phagocytosis of
      degenerated neuronal elements induced by KA.

PMID- 12788214
TI  - Increased dopamine D2 receptor binding and enhanced apomorphine-induced locomotor
      activity in mu-opioid receptor knockout mice.
AB  - Previous studies from our laboratory have indicated possible interactions between
      opioidergic and dopaminergic neurons in the central nervous system. In this
      study, apomorphine-induced locomotor activity and the D1 and D2 subtype dopamine
      receptor binding were examined in mice lacking the mu-opioid receptor genes. The
      ambulatory time, vertical time and total motor distance of locomotor activity
      were measured after administration of apomorphine (2mg/kg, i.p.) for a period of
      90min. The autoradiographic studies of D1 and D2 dopamine receptors were
      conducted using [3H] SCH23390 and [3H] raclopride as ligand, respectively. In
      wild type mice that received apomorphine, 2mg/kg, i.p., the locomotor activity
      such as ambulatory time, vertical time and total motor distance were not
      significantly altered as compared with that of the saline control group. However,
      the locomotor activity measured was significantly increased in the same dose of
      apomorphine treated mu-opioid receptor knockout mice between 5 and 40min after
      administration. The results obtained also show that the binding of D2 dopamine
      receptor in mu-opioid receptor knockout mice was significantly higher than that
      of the wild type in the caudate putamen. However, the binding of the D1 dopamine
      receptor in mu-opioid receptor knockout mice was not significantly different from
      that of the wild type. It appears that the apomorphine treated mu-opioid receptor
      knockout mice showed enhancement in locomotor activity. The enhanced locomotor
      activity may be related to the compensatory up-regulation of D2 dopamine
      receptors in mice lacking mu-opioid receptor genes.

PMID- 12788215
TI  - The use of ultrasound-stimulated acoustic emission in the monitoring of modulus
      changes with temperature.
AB  - It has been previously shown that the amplitude of the ultrasound-stimulated
      acoustic emission (USAE) signal is sensitive to tissue temperature and,
      therefore, can help detect it. Its amplitude, however, is sensitive to both
      acoustical and mechanical parameters, that at most frequencies have opposite
      effects due to temperature. In this paper, we explore the feasibility of using a
      frequency shift of the resonant peaks of the USAE signal for monitoring the
      tissue stiffness variation with temperature. In a numerical simulation, the
      variation of the frequency shift at different temperatures is shown. Then, in a
      series of experiments involving a gel phantom and porcine muscle tissue, the
      frequency shift variation is shown to follow the known stiffness changes due to
      temperature. It is also shown that this shift indicates reversible changes as
      well as the onset of thermal coagulative necrosis. The necrosis is marked by a
      monotonically increasing positive frequency shift. It was thus shown that the
      USAE spectrum peaks undergo a negative shift (or, downshift) when the stiffness
      decreases and a positive shift (or, upshift) when the stiffness increases. The
      experimental frequency shifted around a peak at 22.1-22.5 kHz within a range of 
      250 to 80 Hz and -200 to 250 Hz for the gel and muscle tissue for the
      temperatures of 25-70 and 30-70 degrees C, respectively. Simulation and ex vivo
      experimental results indicate that the USAE frequency shift method can help
      decouple the mechanical from the acoustical parameter dependence as well as
      detect the onset of thermal coagulative necrosis.

PMID- 12788216
TI  - Reflection of structural waves at a solid/liquid interface.
AB  - This paper investigates the reflection characteristics of structural or guided
      waves in rods at a solid/liquid interface. Structural waves, whose wavelengths
      are much larger than the diameter of the rod, are described in a first
      approximation by classical one-dimensional wave theory. The reflection
      characteristics of such waves at a solid/liquid (melting) interface has been
      reported by two different ultrasonic measurement techniques: first, measuring the
      fast regression rate of a melting interface during the burning of metal rod
      samples in an oxygen-enriched environment, and second, monitoring the propagation
      of the solid/liquid interface during the slow melting and solidification of a rod
      sample in a furnace. The second work clearly shows that the major reflection
      occurs from the solid/liquid interface and not the liquid/gas interface as
      predicted by plane longitudinal wave reflectivity theory. The present work
      confirms this observation by reporting on the results of some specially designed
      experiments to identify the main interface of reflection for structural waves in
      rods. Hence, it helps in explaining the fundamental discrepancy between the
      reflection characteristics at a solid/liquid interface between low frequency
      structural waves and high frequency bulk waves, and confirms that the detected
      echo within a burning metallic rod clearly represents a reflection from the
      solid/liquid interface.

PMID- 12788217
TI  - A broad band spectroscopy method for ultrasound wave velocity and attenuation
      measurement in dispersive media.
AB  - In a recent paper, we have shown experimental results of ultrasound wave velocity
      and attenuation coefficient measurement in macroscopic suspensions. The
      experimental method was shortly described. This spectroscopy method allows
      measurement over a broadband frequency spectrum in a strong absorbing and high
      dispersive medium. The originality of the method lies in the automatic signal
      processing that suppress the ambiguity in the determination of the signal phase.
      The present paper deals with the detailed description of the signal processing
      that we use.

PMID- 12788218
TI  - Estimation of critical and viscous frequencies for Biot theory in cancellous
      bone.
AB  - The use of Biot theory for modelling ultrasonic wave propagation in porous media
      involves the definition of a "critical frequency" above which both fast and slow
      compressional waves will, in principle, propagate. Critical frequencies have been
      evaluated for healthy and osteoporotic cancellous bone filled with water or
      marrow, using data from the literature. The range of pore sizes in bone gives
      rise to a critical frequency band rather than a single critical frequency, the
      mean of which is lower for osteoporotic bone than normal bone. However, the
      critical frequency is a theoretical concept and previous researchers considered a
      more realistic "viscous frequency" above which both fast and slow waves may be
      experimentally observed. Viscous frequencies in bone are found to be several
      orders of magnitude greater than calculated critical frequencies. Whereas two
      waves may well be observed at all ultrasonic frequencies for water-filled
      cancellous bone at 20 degrees C, it is probable megahertz frequencies would be
      needed for observation of two waves in vivo.

PMID- 12788219
TI  - Nondestructive evaluation of explosively welded clad rods by resonance acoustic
      spectroscopy.
AB  - A resonance acoustic spectroscopy technique is assessed for nondestructive
      evaluation of explosively welded clad rods. Each rod is modeled as a two-layered
      cylinder with a spring-mass system to represent a thin interfacial layer
      containing the weld. A range of interfacial profiles is generated in a set of
      experimental samples by varying the speed of the explosion that drives the copper
      cladding into the aluminum core. Excellent agreement is achieved between measured
      and calculated values of the resonant frequencies of the system, through
      appropriate adjustment of the interfacial mass and spring constants used in the
      wave scattering calculations. Destructive analysis of the interface in the
      experimental specimens confirms that key features of the interfacial profile may
      be inferred from resonance acoustic spectroscopy analysis applied to ultrasonic
      measurements.

PMID- 12788220
TI  - A new method of spatial compounding imaging.
AB  - A new method of spatial compound imaging is presented that improves image quality
      without the usual requirement to decrease the frame rate. The new method of
      imaging utilizes three transducers for data acquisition. The transducer located
      at the center of the transducer system is a phased array probe that acts as both
      transmitter and receiver. The other transducers are unfocused pistons that act
      only as receivers. Envelope data acquired by each transducer are combined to form
      a final image with improved quality (speckle contrast, target detectability and
      lateral resolution). It is shown that the improvement in speckle contrast depends
      on the correlation between individual images acquired by the transducers. The
      effective aperture approach is used for analytic estimation of the correlation
      between images in order to optimize the lateral separation between transducers.
      Using simulations, several compounding strategies have been performed to find the
      strategy that maximizes image quality. The central frequency of 2.5 MHz is used
      in simulations. Quantitative analysis of simulated B-mode images shows that the
      new method of imaging efficiently improves visibility, detectability, and lateral
      resolution of low contrast regions. The image frame rate is preserved because
      multiple scans are not required for the spatial compounding.

PMID- 12788221
TI  - A new method of ultrasound color flow mapping.
AB  - Conventional ultrasound color flow mapping systems estimate and visualize only
      the axial velocity component. To obtain the transverse velocity component a
      modification of a multiple-beam method is proposed. The new two-dimensional color
      flow mapping system has a small size and consists of three transducers. The
      central transducer is an appodized and focused phased array. The other
      transducers are unfocused probes. Three transducers act as receivers and the
      central transducer operates as a transmitter. All receivers acquire rf scan lines
      that are then processed to estimate three axial velocity components using an
      autocorrelation method. These estimates are then combined to estimate the
      transverse velocity component, taking into account the geometric relationships
      among three transducers. Two algorithms for transverse velocity estimation are
      proposed. The first uses the Doppler angle estimate for calculation of the
      transverse velocity component. The other algorithm calculates the transverse
      velocity component directly from the axial components. The accuracy of the flow
      velocity estimators is estimated by simulations. Analysis of accuracy allows
      choosing the more effective algorithm for two-dimensional velocity estimation,
      which is insensitive to variations of the Doppler angle.

PMID- 12788222
TI  - Propagation of Bleustein-Gulyaev waves in a prestressed layered piezoelectric
      structure.
AB  - Based on the theories of nonlinear continuum mechanics, piezoelectricity and
      elastic waves in solids, theoretical analysis of Bleustein-Gulyaev surface
      acoustic wave propagation in a prestressed layered piezoelectric structure are
      described. Numerical calculations are performed for the case that the layer and
      the substrate are identical LiNbO(3) except that they are polarized in opposite
      directions. It is found that an almost linear behavior of the relative change in
      phase velocity versus the initial stress is obtained for both surface
      electrically free and shorted cases. Potential applications in the design of
      acoustic wave devices are suggested.

PMID- 12788223
TI  - Biochemical and physiological changes in plants as a result of different sonic
      exposures.
AB  - The effects of two different sonic exposures on two vegetables, namely Chinese
      cabbage and cucumber at two growth stages, including seedlings and mature plants
      were investigated. The 3 h exposures included either 20 kHz sound waves or "green
      music" that comprised classic music and natural sounds such as those of birds,
      insects, water, etc. Analysis of variance between groups (ANOVA) was used to
      determine the appropriate statistics parameters for the different treatments.
      Both exposures caused significant elevations in the level of polyamines (PAs) and
      increased uptake of oxygen O(2) in comparison with the controls. For Chinese
      cabbage the highest PAs' levels were determined for both seedlings and mature
      plants that were exposed to "green music". The oxygen uptake in Chinese cabbage
      also increased as a result of sonic exposures, and the highest oxygen uptake was
      also observed after "green music" treatment. For cucumber, the highest content of
      PAs for both seedlings and mature cucumber plants was determined as a result of
      20 kHz ultrasound exposure. 20 kHz exposure of mature plants also resulted in the
      highest level of oxygen uptake. No statistically significant differences in the
      vitamin C level were determined between the different sonic treatments and sham
      exposed vegetables.

PMID- 12788224
TI  - Chaperones and folding of MHC class I molecules in the endoplasmic reticulum.
AB  - In this review we discuss the influence of chaperones on the general phenomena of
      folding as well as on the specific folding of an individual protein, MHC class I.
      MHC class I maturation is a highly sophisticated process in which the folding
      machinery of the endoplasmic reticulum (ER) is heavily involved. Understanding
      the MHC class I maturation per se is important since peptides loaded onto MHC
      class I molecules are the base for antigen presentation generating immune
      responses against virus, intracellular bacteria as well as tumours. This review
      discusses the early stages of MHC class I maturation regarding BiP and calnexin
      association, and differences in MHC class I heavy chain (HC) interaction with
      calnexin and calreticulin are highlighted. Late stage MHC class I maturation with
      focus on the dedicated chaperone tapasin is also discussed.

PMID- 12788225
TI  - Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up
      regulated by modified lipoproteins.
AB  - To study the signaling pathway involved in the regulation of galectin-3
      expression we used phorbol ester to stimulate macrophage differentiation of THP-1
      cells. Treatment with phorbol 12-myristate 13-acetate (PMA) increased
      significantly the level of expression of galectin-3 in THP-1 cells. PMA-induced
      galectin-3 overexpression was blocked by: protein kinase C inhibitors
      staurosporine, calphostin C, and apigenin; tyrosine-specific protein kinase
      inhibitors genistein and tyrphostin A25; PD 98059, a selective inhibitor of
      mitogen-activated protein kinase (MAPK) kinase 1 (MEK1 or MKK1); and SB 203580, a
      specific inhibitor of p38 MAPK. Galectin-3 up-regulation was not affected by
      exposure to two inhibitors of cAMP-dependent protein kinase (PKA), H-89 and
      KT5720. Co-transfection of pPG3.5, a plasmid vector containing the rabbit
      galectin-3 promoter and the constructs pMCL-MKK1 N3 or pRC-RSV-MKK3Glu that
      constitutively express MKK1 and MKK3, raised the activity of galectin-3 promoter
      by 185% and 110%, respectively. Co-transfection with a Ha-Ras expression vector
      stimulated galectin-3 promoter activity approximately 10-fold. Expression of c
      Jun or v-Jun raised the level of galectin-3 promoter activity more the three- and
      fourfold, respectively. Co-transfection of c-Jun and pPG3.5 5'-upstream deletion
      mutants resulted in a reduction of the galectin-3 promoter activity by 50% to
      80%. Transfection of c-Jun, v-Jun or Ha-Ras increased significantly galectin-3
      protein in THP-1 cells. These findings indicated that Ras/MEKK1/MKK1-dependent/AP
      1 signal transduction pathway plays an important role in the expression of
      galectin-3 in PMA-stimulated macrophages. We further investigated the effect of
      modified lipoproteins on galectin-3 expression in macrophages. Murine resident
      peritoneal macrophages loaded with acetylated low-density lipoprotein (AcLDL) or
      oxidized LDL (OxLDL) showed increased galectin-3 protein and mRNA. These results
      showed that treatment of macrophages with PMA or modified lipoproteins results in
      galectin-3 overexpression. These findings may explain the enhanced expression of
      galectin-3 in atherosclerotic foam cells and suggest that Ras/MAPK signal
      transduction pathway is involved in controlling this gene.

PMID- 12788226
TI  - Regulation by estrogen of synthesis and secretion of apolipoprotein A-I in the
      chicken hepatoma cell line, LMH-2A.
AB  - The synthesis and secretion of apolipoprotein A-I (apoA-I) in response to the
      treatment with estrogen were investigated in the chicken hepatoma cell line, LMH
      2A. Exposure of these cells to exogenous estrogen for up to 48 h results in a
      decrease of apoA-I production, as evident from Western blotting,
      immunoprecipitation, and immunofluorescence experiments. Likewise, the secretion
      of apoA-I is also decreased in estrogen-treated cells when compared to controls.
      However, under both conditions, the disappearance of the apoprotein from the
      cells occurs very rapidly and with similar kinetics. The bulk of apoA-I secreted
      from LMH-2A cells is recovered on lipoprotein particles with a buoyant density of
      > or =1.10 g/ml, corresponding to HDL and heavy LDL. Interestingly, apoA-I is
      detectable on apoB-containing lipoproteins by sequential immunoprecipitation,
      suggesting that the two apoproteins co-reside at least on a subfraction of the
      secreted particles, or that apoB- and apoA-I-containing particles interact. These
      interactions are more pronounced in estrogen-treated cells, most likely due to
      the dramatic estrogen-mediated induction of apoB synthesis and secretion.

PMID- 12788227
TI  - Involvement of cytochrome c release and caspase-3 activation in the oxidative
      stress-induced apoptosis in human tendon fibroblasts.
AB  - Our previous studies have demonstrated that oxidative stress and apoptosis are
      involved in human tendon degeneration. The objectives of our current study were
      to investigate the effect of oxidative stress on human tendon cell apoptosis, and
      to explore pathways by which tendon cell apoptosis was induced. In vitro
      oxidative stress was created by exposure of cultured human rotator cuff tendon
      cells to H(2)O(2). Apoptotic cells were assessed by Annexin V-FITC staining and
      necrotic cells by propidium iodide (PI) staining using flow cytometry. Cytochrome
      c and caspase-3 protein expression were detected by Western blotting. A mini
      dialysis unit was employed to increase the protein concentration of the cytosolic
      fraction. Caspase-3 activity was determined by a colorimetric assay. Tendon cell
      apoptosis induced by H(2)O(2) was both dose and time dependent. Addition of
      H(2)O(2) resulted in the release of cytochrome c to the cytosol, and an increase
      of caspase-3 activity and the expression of caspase-3 subunit. The data suggest
      that oxidative stress-induced apoptosis in human tendon fibroblasts is mediated
      via pathway(s) that includes release of cytochrome c from mitochondria to the
      cytosol and activation of caspase-3.

PMID- 12788228
TI  - Menadione causes endothelial barrier failure by a direct effect on intracellular
      thiols, independent of reactive oxidant production.
AB  - Menadione (MQ), a quinone used with cancer chemotherapeutic agents, causes
      cytotoxicity to endothelial cells (EC). Previous studies have suggested that MQ
      induces an oxidative stress and dysfunction in EC by either increasing hydrogen
      peroxide (H(2)O(2)) production or depleting intracellular glutathione (GSH), the
      main intracellular antioxidant. Since a primary function of EC is to form a
      barrier to fluid movement into tissues, protecting organs from edema formation
      and dysfunction, our aim was to see if MQ would cause a barrier dysfunction and
      to ascertain the mechanism. Using diffusional permeability to fluorescein
      isothiocyanate-labeled bovine serum albumin (FITC-BSA) as a measure of barrier
      function, we found that 15 micro M MQ incubated with a bovine pulmonary artery EC
      (BPAEC) monolayer for 4 h produced a profound barrier failure ( approximately 7
      fold increase in permeability) with a parallel fall in glutathione, almost to
      depletion. These two events were highly correlated. Immunofluorescent imaging
      showed formation of paracellular holes consistent with a loss or rearrangement of
      cell-cell and cell-matrix adhesion molecules. H(2)O(2) (100 micro M), a
      concentration which gave about the same increase in permeability as MQ, only
      slightly decreased GSH concentration. Antioxidants, such as catalase (CAT) and
      dimethylthiourea (DMTU), which were able to block the H(2)O(2)-induced changes,
      had no effect on the MQ-induced permeability and GSH changes, suggesting that
      H(2)O(2) was not involved in MQ-induced effects. MQ caused a severe EC
      cytotoxicity as judged by lactate dehydrogenase (LDH) leakage from the EC,
      whereas H(2)O(2) caused only a minor increase. Also, MQ profoundly inhibited the
      activities of glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), key thiol enzymes involved in glutathione and
      ATP metabolism, whereas H(2)O(2) produced only a slight decrease in these
      activities. We conclude that the cytotoxicity of MQ and resulting barrier
      dysfunction correlate with GSH depletion and inactivation of key metabolic
      enzymes, compromising antioxidant defenses, rather than being consistent with
      H(2)O(2)-mediated oxidative stress.

PMID- 12788229
TI  - The Dictyostelium discoideum prespore-specific catalase B functions to control
      late development and to protect spore viability.
AB  - Changes in the levels of reactive oxygen species (ROS) have been associated
      previously with cell differentiation and development in several systems. Thus,
      there is interest in studying the developmental regulation of antioxidant
      enzymes, whose activities may modulate ROS levels and subsequent oxidant-mediated
      signal transduction events in specific tissues. Our recent identification in
      Dictyostelium discoideum of the prespore-specific catalase B (CatB) enzyme
      suggested (a) that the CatB enzyme functions to provide protection to the mature
      spores, and (b) that the CatB enzyme may have a regulatory role in cell
      differentiation and morphogenesis. We have now confirmed both these hypotheses.
      We specifically disrupted the catB gene by homologous recombination. The
      resulting catB null strain displays a 4-h delay in development at the time of
      normal catB gene expression, followed by slow and asynchronous development of
      fruiting bodies, taking 10 h longer than the isogenic parent strain. The
      expression of both prestalk- and prespore-specific genes was altered in the
      mutant both temporally and quantitatively, and the resultant mutant spores had
      increased sensitivity to H(2)O(2). This study supports the idea that CatB
      functions in the development of D. discoideum by regulating the level of ROS, and
      adds to the growing body of evidence for regulatory roles for ROS.

PMID- 12788230
TI  - Requirement of calcium and phosphate ions in expression of sodium-dependent
      vitamin C transporter 2 and osteopontin in MC3T3-E1 osteoblastic cells.
AB  - Osteoclasts dissolve mineralized bone matrix at bone resorption sites and release
      large amounts of calcium (Ca(2+)) and phosphate (PO(4)(3-)) ions into the
      extracellular fluid. However, the exact nature of Ca(2+) and PO(4)(3-) on
      osteoblasts remains unclear. We proposed that Ca(2+) and PO(4)(3-) ions are
      required for the expression of sodium-dependent vitamin C transporter (SVCT) 2
      and a differentiation marker, osteopontin (OPN), in osteoblasts as a response to
      the osteoclastic degradation. Results from Northern blotting indicated that a
      deficiency of Ca(2+) or PO(4)(3-) inhibited both SVCT2 and OPN expression in a
      time-dependent manner, whereas elevated Ca(2+) (1 to 4 mM) or PO(4)(3-) (1 to 4
      mM) dose-dependently induced SVCT2, OPN expression and OPN promoter activity. In
      addition, the L-type calcium channel blocker, nifedipine (5 to 20 micro M) and
      the phosphate transporter inhibitor, foscarnet (0.15 to 0.6 mM), dose-dependently
      abolished Ca(2+)- and PO(4)(3-)-induced SVCT2, OPN expression and OPN promoter
      activity. Furthermore, the results from L-ascorbic acid uptake assay and Western
      blotting indicated that the stimulatory effect of Ca(2+) and PO(4)(3-) on
      functional SVCT2 protein expression. These findings suggested that Ca(2+) and
      PO(4)(3-) regulate osteoblastic phenotype by entering into cells to stimulate
      SVCT2 and OPN expression.

PMID- 12788231
TI  - Comparison between schistosomiasis transmission modelings considering acquired
      immunity and age-structured contact pattern with infested water.
AB  - In order to analyze the effects of acquired immunity and the contact pattern with
      infested water on the overall transmission of schistosomiasis, a semi-stochastic
      model is proposed. The model's assumptions are the simplest possible to enhance
      the differences between two hypotheses. With respect to the human host, it is
      assumed the mounting of an immune response after elapsing a fixed period of time
      L from the first infection, which is partially effective and never lost. With
      respect to the contact pattern with infested water, it is assumed a decreasing
      age-related function. Both models are compared to a purely random model, which is
      taken as the basic model.

PMID- 12788232
TI  - Effects of epistasis on phenotypic robustness in metabolic pathways.
AB  - It is an open question whether phenomena such as phenotypic robustness to
      mutation evolve as adaptations or are simply an inherent property of genetic
      systems. As a case study, we examine this question with regard to dominance in
      metabolic physiology. Traditionally the conclusion that has been derived from
      Metabolic Control Analysis has been that dominance is an inevitable property of
      multi-enzyme systems and hence does not require an evolutionary explanation. This
      view is based on a mathematical result commonly referred to as the flux summation
      theorem. However it is shown here that for mutations involving finite changes (of
      any magnitude) in enzyme concentration, the flux summation theorem can only hold
      in a very restricted set of conditions. Using both analytical and simulation
      results we show that for finite changes, the summation theorem is only valid in
      cases where the relationship between genotype and phenotype is linear and devoid
      of non-linearities in the form of epistasis. Such an absence of epistasis is
      unlikely in metabolic systems. As an example, we show that epistasis can arise in
      scenarios where we assume generic non-linearities such as those caused by enzyme
      saturation. In such cases dominance levels can be modified by mutations that
      affect saturation levels. The implication is that dominance is not a necessary
      property of metabolic systems and that it can be subject to evolutionary
      modification.

PMID- 12788234
TI  - Asymptotics and bioavailability in multicompartment pharmacokinetic models with
      enterohepatic circulation.
AB  - Analysing discrete as well as continuous linear autonomous pharmacokinetic
      models, it is shown that their asymptotic behaviour is independent of the rates
      of kinetic processes and timing of drug application. Consequently, for the
      description of pharmacokinetic endpoints, i.e. the total amounts of drug
      eliminated through different organs under various ways of administration, in such
      a model the knowledge of total amounts delivered to individual compartments and
      its transition probability matrix P=[p(ij)] is sufficient.A design and analysis
      of a 9-compartment pharmacokinetic model with enterohepatic circulation (EHC),
      avoiding several common simplifications, test the applicability of our method.
      The central compartment of the model is the liver acting as filter and linking
      the systemic and enterohepatic circulation. Explicit formulas are given for
      pharmacokinetic endpoints of the model using the elements of the transition
      probability matrix P. Conversely, the transition probabilities are determined in
      terms of certain measurable pharmacokinetic endpoints and the flow rates through
      the kidneys, liver and the cardiac output, contributing that way to the
      structural identifiability problem. As a further consequence, the bioavailability
      of the drug with and without EHC can be determined and the efficiency of EHC
      expressed as the 'probability' of the enterohepatic cycle.Finally, we apply our
      method to analyse and compare various pharmacokinetic models, describing the EHC
      of drugs, based on some previously published articles.

PMID- 12788233
TI  - Numerical non-identifiability regions of the minimal model of glucose kinetics:
      superiority of Bayesian estimation.
AB  - The so-called minimal model (MM) of glucose kinetics is widely employed to
      estimate insulin sensitivity (S(I)) both in clinical and epidemiological studies.
      Usually, MM is numerically identified by resorting to Fisherian parameter
      estimation techniques, such as maximum likelihood (ML). However, unsatisfactory
      parameter estimates are sometimes obtained, e.g. S(I) estimates virtually zero or
      unrealistically high and affected by very large uncertainty, making the practical
      use of MM difficult. The first result of this paper concerns the mathematical
      demonstration that these estimation difficulties are inherent to MM structure
      which can expose S(I) estimation to the risk of numerical non-identifiability.
      The second result is based on simulation studies and shows that Bayesian
      parameter estimation techniques are less sensitive, in terms of both accuracy and
      precision, than the Fisherian ones with respect to these difficulties. In
      conclusion, Bayesian parameter estimation can successfully deal with difficulties
      of MM identification inherently due to its structure.

PMID- 12788235
TI  - Using network models to approximate spatial point-process models.
AB  - Spatial effects are fundamental to ecological and epidemiological systems, yet
      the incorporation of space into models is potentially complex. Fixed-edge network
      models (i.e. networks where each edge has the same fixed strength of interaction)
      are widely used to study spatial processes but they make simplistic assumptions
      about spatial scale and structure. Furthermore, it can be difficult to
      parameterize such models with empirical data. By comparison, spatial point
      process models are often more realistic than fixed-edge network models, but are
      also more difficult to analyze. Here we develop a moment closure technique that
      allows us to define a fixed-edge network model which predicts the prevalence and
      rate of epidemic spread of a continuous spatial point-process epidemic model.
      This approach provides a systematic method for accurate parameterization of
      network models using data from continuously distributed populations (such as data
      on dispersal kernels). Insofar as point-process models are accurate
      representations of real spatial biological systems, our example also supports the
      view that network models are realistic representations of space.

PMID- 12788236
TI  - Pediatric bipolar disorder coming of age.

PMID- 12788237
TI  - Pediatric bipolar disorder: the parent advocacy perspective.

PMID- 12788238
TI  - Convergence between structured diagnostic interviews and clinical assessment on
      the diagnosis of pediatric-onset mania.
AB  - BACKGROUND: Uncertainties remain as to the utility of structured diagnostic
      methodology to aid in the diagnosis of manic symptomatology in youth. To this
      end, this study compared structured diagnostic interview based diagnoses of mania
      in children and adolescents with that of an expert clinician. METHODS: We
      separately and independently assessed 69 youths recruited for a study of mania in
      childhood, all but 2 of whom experienced mania, with a structured diagnostic
      interview administered by trained psychometricians and a clinical assessment by a
      board-certified child and adolescent psychiatrist (JW) who was blind to the
      structured interview results. RESULTS: Structured interviews and clinical
      evaluations converged in all but two cases (67 of 69 or 97% agreement). In one
      discrepant case, the structured interview diagnosed a full case of mania, but the
      clinical interview diagnosed cyclothymia/subthreshold mania; in the other
      discrepant case, the structured interview failed to diagnose mania, but the
      clinical interview did diagnose mania. CONCLUSIONS: In children referred for
      evaluation of suspected bipolar disorder, a structured interview diagnosis of
      mania is very likely to be corroborated by a clinical interview.

PMID- 12788239
TI  - Bipolar offspring: a window into bipolar disorder evolution.
AB  - Children of parents with bipolar disorder (bipolar offspring) represent a rich
      cohort for study with potential for illumination of prodromal forms of bipolar
      disorder. Due to their high-risk nature, bipolar offspring may present
      phenomenological, temperamental, and biological clues to early presentations of
      bipolar disorder. This article reviews the evidence for establishing bipolar
      offspring as a high-risk cohort, the studies which point to possible prodromal
      states in bipolar offspring, biological findings in bipolar offspring which may
      be indicators of even higher risk for bipolar disorder, initial attempts at early
      intervention in prodromal pediatric bipolar disorder, and implications for future
      research.

PMID- 12788240
TI  - Can a subtype of conduct disorder linked to bipolar disorder be identified?
      Integration of findings from the Massachusetts General Hospital Pediatric
      Psychopharmacology Research Program.
AB  - Our intent was to investigate systematically the overlap between conduct disorder
      (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic
      symptoms were secondary to the other disorder and that children with the two
      disorders would have correlates of both. Results from a series of programmatic
      studies examining phenotypic features of bipolar and conduct disorder alone or
      combined in probands and relatives were evaluated within and without the context
      of ADHD. Examination of the clinical features, patterns of psychiatric
      comorbidity, functioning in multiple domains, and familiality showed that
      children with CD and BPD had similar features of each disorder irrespective of
      the comorbidity with the other disorder. Our data suggest that when BPD and CD co
      occur in children, both are correctly diagnosed. In these comorbid cases, CD
      symptoms should not be viewed as secondary to BPD, and manic symptoms should not
      be viewed as secondary to CD.

PMID- 12788241
TI  - Is preadolescent mania the same condition as adult mania? A British perspective.
AB  - Until relatively recently, the prevailing view was that mania was uncommon in
      preadolescent children. In the past 15 years, however, there has been increasing
      interest in the idea that mania may be much more common at younger ages than
      previously recognized. This article is concerned with the issue of whether
      preadolescent mania represents the same kind of problem as adult mania. It
      reviews concepts of bipolar disorder and mania in adults and preadolescents, some
      of the issue that arise in diagnosing mania in children, and the evidence for
      continuities between preadolescent and adult mania. The diagnosis of mania in
      preadolescent children often requires that inferences are made about the meaning
      of some symptoms but it is not always clear that these inferences are valid. It
      is concluded that the extant evidence does not provide a clear conclusion about
      the links between preadolescent and adult mania. More work is needed on the
      phenomenology and diagnosis of mania in children, on its natural history and on
      its familial correlates.

PMID- 12788242
TI  - The genetics of pediatric-onset bipolar disorder.
AB  - Although bipolar disorder in adults has been extensively studied, early-onset
      forms of the disorder have received less attention. We review several lines of
      evidence indicating that pediatric- and early adolescent-onset bipolar disorder
      cases may prove the most useful for identifying susceptibility genes. Family
      studies have consistently found a higher rate of bipolar disorder among the
      relatives of early-onset bipolar disorder patients than in relatives of later
      onset cases, which supports the notion of a larger genetic contribution to the
      early-onset cases. Comorbid pediatric bipolar disorder and attention
      deficit/hyperactivity disorder (ADHD) may also define a familial subtype of ADHD
      or bipolar disorder that is strongly influenced by genetic factors and may,
      therefore, be useful in molecular genetic studies. There are no twin and adoption
      studies of pediatric bipolar disorder, but the heritability of this subtype is
      expected to be high given the results from family studies. Thus, pediatric- and
      early adolescent-onset bipolar disorder may represent a genetically loaded and
      homogeneous subtype of bipolar disorder, which, if used in genetic linkage and
      association studies, should increase power to detect risk loci and alleles.

PMID- 12788243
TI  - Combination pharmacotherapy in children and adolescents with bipolar disorder.
AB  - BACKGROUND: The purpose of this study was to develop prospective data on the
      effectiveness of combination pharmacotherapy of children and adolescents with
      bipolar disorder during a 6-month period of prospective, semi-naturalistic
      treatment. METHODS: Thirty-five subjects, with a mean age of 11 years, were
      treated in the extension phase of this study after having received 6-8 weeks of
      acute treatment with a single mood stabilizer. The extension phase of this study
      lasted for another 16 weeks, for a total of 24 weeks of prospective treatment.
      During this study phase, subjects were openly treated, and they could have their
      acute-phase mood stabilizer switched or augmented with another mood stabilizer, a
      stimulant, an antidepressant agent, or antipsychotic agent, if they were assessed
      to be a nonresponder to monotherapy with their initial mood stabilizer. RESULTS:
      During the extension phase of treatment, 20 of 35 subjects (58%) required
      treatment with one or two mood stabilizers and either a stimulant, an atypical
      antipsychotic agent, or an antidepressant agent. The response rate to combination
      therapy was very good, with 80% of subjects treated responding to combination
      therapy with two mood stabilizers after not responding to monotherapy with a mood
      stabilizer. CONCLUSIONS: This study suggests that children and adolescents with
      bipolar disorder are similar to adults with bipolar disorder, who also frequently
      require combination therapy.

PMID- 12788244
TI  - Behavioral inhibition and disinhibition as hypothesized precursors to
      psychopathology: implications for pediatric bipolar disorder.
AB  - Attention has been devoted over the past two decades to the identification of
      temperamental risk factors for child psychopathology. These qualities, evident in
      toddlerhood or earlier, have the advantage of being measurable in standardized
      laboratory observations well before children reach the age of onset or diagnosis
      of psychiatric disorders. Our group's programmatic research over the past 15
      years, and that of others, has provided evidence linking "behavioral inhibition
      to the unfamiliar" in toddlerhood or early childhood with later social anxiety
      disorder. In addition, recent results by our group have suggested that
      "behavioral disinhibition" in early childhood, measured by the same laboratory
      methods, may be linked with later disruptive behavior and comorbid mood
      disorders. In this article, we discuss our approach to the study of temperamental
      precursors to disorders in high-risk children, summarize the literature linking
      behavioral inhibition and disinhibition to later psychopathology, and suggest
      directions to take in applying this methodology to the search for temperamental
      precursors to pediatric bipolar disorder.

PMID- 12788245
TI  - Family psychoeducation: an adjunctive intervention for children with bipolar
      disorder.
AB  - Childhood onset bipolar disorder is associated with significant morbidity and
      mortality, yet effective treatment strategies have remained underdeveloped and
      understudied. While some headway is being made vis-a-vis pharmacologic
      treatments, empirical efforts have not focused on adjunctive psychosocial
      interventions for childhood bipolar disorder. In this review, we discuss
      psychoeducation, delivered via workshops, multifamily psychoeducation groups, or
      individual-family psychoeducation, as an adjunct to the ongoing pharmacotherapy,
      psychotherapy, and school-based interventions for children with bipolar disorder.
      We review the theoretical rationale for psychoeducation, including expressed
      emotion and caregiver concordance; summarize findings in the adult literature;
      and then describe our development and testing of psychoeducational interventions
      for mood-impaired children. Data from three pilot studies are reviewed, and
      progress on two studies currently underway is presented. We conclude with current
      limitations of psychoeducation and recommendations for future study to develop
      psychoeducation as an empirically supported adjunctive intervention for children
      with bipolar disorder.

PMID- 12788246
TI  - Researching the pathophysiology of pediatric bipolar disorder.
AB  - We suggest that the core feature of bipolar disorder (BPD) is marked state
      fluctuations. The pathophysiology of switches into depressed, irritable, and
      extreme positive valence states requires study, with the latter deserving
      particular focus because it represents a pathognomonic feature of BPD in both
      adults and children. Hypotheses regarding the pathophysiology of pediatric BPD
      must account for these marked state fluctuations as well as for specific
      developmental aspects of the illness. These developmental aspects include marked
      irritability (in addition to euphoria and depression) and very rapid cycles,
      along with high rates of attention-deficit/hyperactivity disorder. We review
      research on neural mechanisms underlying positive valence states and state
      regulation, focusing on those data relevant to BPD and to development.
      Researchers are beginning to explore the response of manic patients and control
      subjects to positive affective stimuli, and considerable research in both
      nonhuman primates and humans has focused on the cortico-limbic-striatal circuits
      mediating responses to rewarding stimuli. In control subjects, positive affect
      affects cognition, and data indicate that prefrontal electroencephalogram
      asymmetry may differ between control subjects with consistently positive affect
      and those with more negative affect; however, this latter generalization may not
      apply to adolescents. With regard to the pathophysiology of state switching in
      pediatric BPD, data in control subjects indicating that attention regulation
      plays a role in emotion regulation may be germane. In addition, research
      detailing physiologic and psychological responses to negative emotional stimuli
      in bipolar patients and control subjects may increase our understanding of the
      mechanisms underlying both irritability and rapid cycling seen in children with
      BPD. Potential foci for research on the pathophysiology of pediatric BPD include
      reactivity to standardized positive and negative emotional stimuli, and the
      interaction between emotion regulation and attentional processes.

PMID- 12788247
TI  - A preliminary meta-analysis of the child behavior checklist in pediatric bipolar
      disorder.
AB  - BACKGROUND: A possible explanation for the ongoing controversy surrounding
      pediatric bipolar disorder is that differences in assessment methodologies lead
      to conflicting results. One way to address methodological differences in
      assessment across studies is to use a single standardized assessment of
      psychopathology to calibrate the findings reported in different studies. To this
      end, we conducted a meta-analysis of several studies that have employed the Child
      Behavior Checklist in the assessment of children with a diagnosis of bipolar
      disorder. METHODS: MEDLINE was searched for all publications that utilized the
      Child Behavior Checklist in addition to structured diagnostic interviews to
      assess pediatric bipolar disorder. Random effects models were used to calculate
      combined estimates of Child Behavior Checklist clinical subscales. RESULTS:
      Children with bipolar disorder had scaled scores of >70 in the Aggression,
      Attention Problems, and Anxious/Depressed subscales of the Child Behavior
      Checklist. The Child Behavior Checklist was useful in distinguishing bipolar from
      attention-deficit/hyperactivity disorder subjects. CONCLUSIONS: While there was a
      significant heterogeneity in estimates between studies, a consistent pattern of
      elevations in inattention/hyperactivity, depression/anxiety, and aggression was
      identified.

PMID- 12788248
TI  - Rationale, design, and methods of the systematic treatment enhancement program
      for bipolar disorder (STEP-BD).
AB  - The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was
      conceived in response to a National Institute of Mental Health initiative seeking
      a public health intervention model that could generate externally valid answers
      to treatment effectiveness questions related to bipolar disorder. STEP-BD, like
      all effectiveness research, faces many design challenges, including how to do the
      following: recruit a representative sample of patients for studies of readily
      available treatments; implement a common intervention strategy across diverse
      settings; determine outcomes for patients in multiple phases of illness; make
      provisions for testing as yet undetermined new treatments; integrate adjunctive
      psychosocial interventions; and avoid biases due to subject drop-out and last
      observation-carried-forward data analyses. To meet these challenges, STEP-BD uses
      a hybrid design to collect longitudinal data as patients make transitions between
      naturalistic studies and randomized clinical trials. Bipolar patients of every
      subtype with age >/= 15 years are accessioned into a study registry. All patients
      receive a systematic assessment battery at entry and are treated by a
      psychiatrist (trained to deliver care and measure outcomes in patients with
      bipolar disorder) using a series of model practice procedures consistent with
      expert recommendations. At every follow-up visit, the treating psychiatrist
      completes a standardized assessment and assigns an operationalized clinical
      status based on DSM-IV criteria. Patients have independent evaluations at regular
      intervals throughout the study and remain under the care of the same treating
      psychiatrist while making transitions between randomized care studies and the
      standard care treatment pathways. This article reviews the methodology used for
      the selection and certification of the clinical treatment centers, training study
      personnel, the general approach to clinical management, and the sequential
      treatment strategies offered in the STEP-BD standard and randomized care pathways
      for bipolar depression and relapse prevention.

PMID- 12788249
TI  - Juvenile bipolar disorder in Brazil: clinical and treatment findings.
AB  - BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in
      children and adolescents outside North America, this investigation aims to
      describe clinical features, pattern of comorbidities, and response to
      pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a
      pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a
      retrospective chart review of all patients under age 15 with BD diagnoses who
      were evaluated and treated in our clinic from 1998-2001. A comparison sample of
      subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n =
      362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was
      7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in
      91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%).
      Children with BD had significantly higher rates of abnormally elevated CBCL
      scores in the externalizing dimension, anxiety and depression, delinquent
      behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD
      patients (78%) needed combination drug therapy to achieve symptomatic control.
      CONCLUSIONS: Our results replicate clinical and treatment findings from U.S.
      investigations in a different culture demonstrating that juvenile BD is not a
      rare disorder in clinical samples.

PMID- 12788250
TI  - Clinical implications of pervasive manic symptoms in children.
AB  - BACKGROUND: Prior investigations of cross-informant agreement among parents,
      teachers, and clinicians about externalizing and internalizing problems have not
      directly addressed agreement about manic symptoms. METHODS: We identified three
      groups from a large cohort of youths, aged 8-12 years, treated on an inpatient
      unit. All 108 participants met criteria for an externalizing disorder, based on a
      semi-structured diagnostic interview. Of these, 49 did not have manic symptoms
      endorsed by either the parent or a teacher; 34 had manic symptoms reported by the
      parent only, and 25 had pervasive manic symptoms (i.e., corroborated by both
      sources). RESULTS: The "corroborated mania" group consistently showed the most
      disruptive behavior on the inpatient unit, the worst behavior problems on
      multiple scales, and the longest admission durations. The "parent-only" group
      scored in the midrange on all of these measures, with group differences typically
      representing small to medium effect sizes. The "externalizing only" group
      consistently scored lowest on all dependent measures, with the differences
      representing large to extremely large effects when compared with the corroborated
      mania group and medium effects as compared with the parent-only group.
      CONCLUSIONS: Youths for whom multiple informants report manic symptoms appear
      likely to have more severe symptom presentation and more complicated, refractory
      courses than do youths without manic symptoms.

PMID- 12788251
TI  - Decreased N-acetylaspartate in children with familial bipolar disorder.
AB  - BACKGROUND: Relatively low levels of brain N-acetylaspartate, as measured by
      magnetic resonance spectroscopy, may indicate decreased neuronal density or
      viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported
      to be decreased in adults with bipolar disorder. We used proton magnetic
      resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate
      levels in children with familial bipolar disorder. METHODS: Subjects were 15
      children and adolescents with bipolar disorder, who each had at least one parent
      with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for
      subjects and controls. Subjects were allowed to continue current medications.
      Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3)
      voxels placed in left and right dorsolateral prefrontal cortex. RESULTS: Bipolar
      subjects had lower N-acetylaspartate/Creatine ratios only in the right
      dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline
      levels were found. CONCLUSIONS: Children and adolescents with bipolar disorder
      may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults
      with BD, indicating a common neuropathophysiology. Longitudinal studies of at
      risk children before the onset and during the early course of bipolar disorder
      are needed to determine the role of prefrontal N-acetylaspartate as a possible
      risk marker and/or indication of early bipolar illness progression.

PMID- 12788252
TI  - The effect of the dam-calf relationship on serostatus to Neospora caninum on 20
      Costa Rican dairy farms.
AB  - An epidemiological study was conducted on 20 dairy herds previously diagnosed as
      seropositive for Neospora caninum. The number of females per farm varies from 41
      to 296. All females present on the farms were bled once in the period of July and
      August 2000. A total of 3002 females were bled. An indirect ELISA was used to
      determine the serostatus of the animals. The analysis of the data was performed
      in four steps: (1) descriptive statistics about the serological status and
      general characteristics of the cattle; (2) calculation of vertical and horizontal
      transmission; (3) an univariate analysis and, (4) a multivariate logistic
      regression analysis with herd as random effect. The within-herd seroprevalence
      varied between 25.0% (34/136) and 70.5% (203/288). Seven hundred and forty-seven
      dam-daughter pairs were available, involving daughters of any age. Daughters in
      the specific age-class of 2- and 3-years old had a higher seroprevalence (P<0.01)
      compared with younger and older age-classes. The risk of being seropositive when
      being born to a mother that tested seropositive (prevalence ratio (PR)) was 2.8
      fold increased which coincides with a 5.3-fold increased odds. The probability of
      horizontal infection amounts to 0.22. The probability of a seropositive offspring
      due to vertical transmission was 0.64 (attributable fraction among exposed
      (AFexp)). The multivariate logistic regression showed a significant 6.0-fold
      increased odds for being seropositive when born from a seropositive mother. Also
      the within-herd seroprevalence level was significantly associated with the
      serostatus of the daughters. In the specific conditions of the dairy herds
      involved in this study, the serostatus of the cows should be not used as a
      predictor of the serostatus of daughters due to the increased probability of
      horizontal transmission.

PMID- 12788253
TI  - Molecular studies on Babesia, Theileria and Hepatozoon in southern Europe. Part
      II. Phylogenetic analysis and evolutionary history.
AB  - Following a study on molecular epizootiology of Hepatozoon canis and piroplasmids
      (Babesia spp. and Theileria spp.) in southern Europe, newly obtained sequences of
      18s rRNA gene were used for phylogenetic analysis. Partial sequences were
      analysed in isolates showing high degree of homology (>99%) with previous GenBank
      entries: H. canis, B. canis vogeli, B. equi (two isolates, Spain1 and Spain2), T.
      annulata and Theileria sp. The complete gene sequences were used for B. ovis and
      B. bovis, that showed lower homology (<95%) with rapport to previously reported
      species or isolates. A first set of phylogenetic trees constructed with partial
      18s rRNA sequences showed that most European isolates clustered unambiguously
      with previously described species, so that minor sequence dissimilarities found
      are due probably to strain variations. The second set of phylogenetic trees was
      made using the complete 18s rRNA sequences of 44 species from GenBank and the
      newly sequenced B. ovis and B. bovis. The analysis revealed for the first time a
      division of piroplasmids in five clades: (1) B. microti group, with B. rodhaini,
      B. felis, B. leo, B. microti and T. annae (proposed name for the group, without
      taxonomic value: Archaeopiroplasmids), (2) Western USA Theilerid-like group
      (proposed name: Prototheilerids), (3) Theileria group, containing all Theileria
      species from Bovinae (proposed name: Theilerids), (4) A first group of Babesia
      species including B. canis and B. gibsoni from canids together with B. divergens
      and B. odocoilei (proposed name: Babesids), (5) A second group composed mainly by
      Babesia species from ungulates: B. caballi, B. bigemina, B. ovis, B. bovis and
      Babesia sp. from cow (proposed name: Ungulibabesids). The bootstrap support
      obtained with several analytical procedures for this new dicotomy of Babesiidae
      was always very high. Taking into account the present phylogenetic analysis and
      additional paleogeographic, parasitological and zoological evidences, two
      hypothesis on the origin and evolution of piroplasmids groups are presented.

PMID- 12788254
TI  - Merogony in in vitro cultures of Theileria parva.
AB  - In vitro studies were focussed on the duration and cessation of merogony in
      Theileria parva infected blood lymphocyte cell cultures. The cultures were
      infected using purified tick stabilates as an alternative to in vitro infections,
      using sporozoites obtained by labour intensive dissections of salivary glands
      from infected ticks. After establishment of infection in peripheral blood
      lymphocytes (PBL), merozoites were temporarily produced for about 2 months after
      which lymphoblasts only contained schizonts.

PMID- 12788255
TI  - The effect of treatment with eprinomectin on lungworms at early patency on the
      development of immunity in young cattle.
AB  - An experiment was carried out to study the effect of topical application of
      eprinomectin at early patency on the build up of infection and development of
      protection against Dictyocaulus viviparus in young cattle. Three groups of six
      calves were used and parasitological and blood variables were monitored at weekly
      intervals throughout the trial. At the start of the experiment calves in groups A
      and B were experimentally inoculated with 100 D. viviparus infective third-stage
      larvae (L3) for five consecutive days, whereas calves in group C served as
      uninfected controls. The calves in group A were each treated with eprinomectin
      (0.5mg/kg bodyweight) in a pour-on formulation at early patency at day 24 post
      the first inoculation, whereas the calves in groups B and C were left untreated.
      Seven weeks following anthelmintic treatment all groups were challenged with 1500
      L3. Another 4 weeks later the animals were sacrificed and established worms in
      the lungs were counted. Moderate transient signs of lungworm disease occurred
      both in groups A and B. However, group B calves were found to be about 8 times
      more resistant than those in group A, whereas the naive infection controls in
      Group C was found to be about 35 times more susceptible to infection. Also the
      ELISA values showed that the course of infection was different between
      experimental groups. The eosinophil counts prior to and at the time of slaughter
      indicate that immunity was involved in the protection and the response was
      correlated with previous exposure and worm load. Weight gains differed
      significantly, but only between groups A and C and between groups B and C that on
      an average were approximately 13kg heavier at the termination of the experiment.
      It was concluded that eprinomectin was effective against established adult
      lungworms. However, the untreated calves (group B) developed a more marked
      resistance to lungworms compared to those that were subjected to anthelmintic
      treatment at early patency (group A). On the other hand, the cumulative number of
      excreted larvae was on an average 43 times higher in group B as compared to group
      A. Consequently, infected calves that remain out on pasture should be treated.
      This will restrain transmission of the parasite despite the fact that immunity is
      deteriorated.

PMID- 12788256
TI  - A simple pump-assisted method for collecting live, undamaged Psoroptes ovis from
      sheep using circulating saline.
AB  - The availability of large numbers of undamaged sheep scab mites, Psoroptes ovis,
      would be beneficial for discovery screening and development trials. There are
      several reported procedures for removing scab mites from sheep but they have
      limitations. To overcome this, a simple but versatile method employing the use of
      pumped saline was developed to remove all stages of the P. ovis mite from sheep.
      The method takes no more than 2 min to remove mites from the selected site with
      relative ease and is not affected by the condition of the fleece or lesion. The
      number of mites removed with the new method was 5-10 times more than detected by
      visual examination. These mites were undamaged and survived off-host for up to 16
      days. The robust, portable equipment is easy to use under field conditions,
      making this method suitable for use as a diagnostic tool for early detection and
      monitoring of scab mites thus providing opportunities for development of novel
      alternative control strategies.

PMID- 12788257
TI  - PCR-based detection of canine Leishmania infections in formalin-fixed and
      paraffin-embedded skin biopsies: elaboration of a protocol for quality assessment
      of the diagnostic amplification reaction.
AB  - Diagnosis of the cutaneous form of canine leishmaniosis is mostly performed by
      histological or immunohistological examination of skin biopsies. In modern
      histology, the polymerase chain reaction (PCR) has gained increasing importance
      as a complementary tool to directly demonstrate the presence of parasite DNA in
      the tissue sections. For the present study, a previously described Leishmania-PCR
      has been further developed and optimised in view of its practicability for
      routine histological application. Since formalin-fixation of histological
      specimens causes partial DNA-destruction, which may hamper diagnostic PCR
      analysis, primers specific for the highly conserved alpha-actin gene sequences
      were used to pre-diagnostically assess the isolated sample-DNA for its
      functionality in a PCR-reaction. This alpha-actin-specific PCR detects DNA from a
      large variety of mammalian species and thus exhibits relevance for both human and
      veterinary medical application. A recombinant internal positive control was
      introduced to monitor possible sample-related inhibitory effects during the
      amplification reaction. We performed a retrospective evaluative study with 18
      formalin-fixed samples from dogs with suspected or proven leishmaniosis. Six
      samples were PCR-incompatible. In turn, 9 of the other 12 samples were PCR
      positive, and immunohistochemical results matched these findings. Based on these
      technical achievements, the Leishmania-PCR proved to be a valuable tool to
      complement conventional histological and immunohistological methods for diagnosis
      of cutaneous leishmaniosis in formalin-fixed, paraffin-embedded skin biopsies.

PMID- 12788258
TI  - Seroprevalence of canine dirofilariosis in South Korea.
AB  - Eight-hundred and forty eight dogs (480 females and 368 males) not on
      chemoprophylaxis were examined for Dirofilaria immitis infection from 2001 to
      2002. Three-hundred and thirty nine (40.0%) of 848 samples tested with antigen
      detecting ELISA kits showed positive reaction for D. immitis antigen. More male
      (43.5%) than female (37.3%) dogs were affected in this study, although there was
      no significant difference between both groups. Chi2 analysis showed that female
      and male dogs of shoreline areas had higher significant prevalence than other
      areas (P<0.001), respectively. The mean overall positive rates of heartworm
      infection were 10.4% in dogs <2-year-old group, 46.5% in 2-4-year-old group,
      48.4% in 4-6-year-old group and 50.3% in >6-year-old group. The older the age,
      the higher the prevalence of D. immitis infection in this study. Chi2 analysis
      revealed a significant higher prevalence in 4-6-year-old group (100%) of
      shoreline areas and in 2-4-old-year group (51.2%) of urban areas (Chungnam
      province), respectively (P<0.001), and also revealed that the over 6-year-old
      group (50.3%) in mean overall prevalence had the significant higher prevalence
      than other age group (P<0.001). In climate comparison, our data showed that
      shoreline areas (69.5%) had the significant higher prevalence than urban areas
      and mountain areas (P<0.001). This survey confirms that the prevalence of canine
      heartworm infection increases, and also that the prevalence in shoreline areas is
      higher than in other areas in South Korea.

PMID- 12788259
TI  - Alcohol expectancies, alcohol consumption, and problem drinking: the moderating
      role of family history.
AB  - The purpose of this investigation was to examine the moderating role of family
      history (FH) of alcohol use disorders on the association between positive alcohol
      expectancies and drinking behavior (quantity/frequency of drinking and alcohol
      related problems). Lifetime DSM-III-R diagnoses of alcohol abuse/dependence in
      probands from the Yale Family Study were used to classify FH status of adult
      relatives, yielding 149 relatives of probands with alcohol abuse/dependence and
      110 relatives of controls. Significant main effects were found for FH of
      alcoholism on problem drinking symptoms and for alcohol expectancies concerning
      both problem drinking symptoms and quantity/frequency of alcohol use. Regarding
      moderating effects, there was a significant interaction between alcohol
      expectancies and FH only for problem drinking symptoms. When familial density of
      alcoholism was examined as a moderator, significant effects were found for all
      drinking variables, thus demonstrating that the degree to which alcohol
      expectancies was associated with the drinking outcomes varied by the extent to
      which alcohol use disorders clustered in families. The findings are discussed in
      terms of the interaction of alcohol-related risk factors and the importance of
      using multiple indicators of familial vulnerability.

PMID- 12788260
TI  - Performance of recently detoxified patients with alcoholism on a
      neuropsychological screening test.
AB  - OBJECTIVE: Early in recovery from alcoholism, cognitive deficits may compromise
      patients' utilization of rehabilitative information. Cognitive impairment in a
      sample of newly detoxified inpatients with alcoholism was examined using the
      Neurobehavioral Cognitive Status Examination (NCSE). METHODS: Consecutively
      admitted psychiatric inpatients (N=233) with an alcohol-related primary diagnosis
      (63% male, mean age 46.3) were administered the NCSE following medical
      stabilization. Within-samples differences between age and diagnostic groups were
      examined and scores were compared to normative samples. RESULTS: Inpatients older
      than 50 demonstrated significant cognitive deficits for all scales except
      Attention. In comparison with normative samples, patients with alcoholism
      produced lower scores, with the most pronounced deficits among middle-aged
      patients. In alcohol-abusing patients with medical comorbidities, language
      deficits and more severe memory deficits were observed. Abuse severity or
      comorbid psychiatric disorder produced no differences in NCSE scores.
      CONCLUSIONS: Neuropsychological screening following detoxification in patients
      diagnosed with an alcohol disorder reflected the effects of increased age and
      medical comorbidity. Our finding of frequent deficits in abstraction,
      comprehension, and memory suggests that cognitive-behavioral treatments for
      inpatients may be less effective if cognitive impairment is not considered.

PMID- 12788261
TI  - Anxiety sensitivity, controllability, and experiential avoidance and their
      relation to drug of choice and addiction severity in a residential sample of
      substance-abusing veterans.
AB  - The aim of the present study was to evaluate anxiety-related psychological risk
      factors (e.g., anxiety sensitivity, perceived uncontrollability, emotional
      avoidance) and their relation to drug of choice and addiction severity in an
      inpatient residential substance abuse population. Fully detoxified veterans
      (N=94) meeting criteria for Axis I substance abuse disorders were enrolled in a
      28-day residential substance abuse treatment program and completed the following
      measures at intake and discharge: Anxiety Sensitivity Index, Body Sensations
      Questionnaire (BSQ), Acceptance and Action Questionnaire (AAQ), Beck Depression
      Inventory (BDI; intake only), and the Anxiety Control Questionnaire (ACQ).
      Consistent with the expectation, veterans who reported more distress over bodily
      sensations (anxiety sensitivity, BSQ) and depressive symptoms (BDI) were more
      likely to avoid experiencing negative affect (AAQ) and perceived themselves as
      lacking in control (ACQ). Further, extent of avoidance, and to a lesser extent,
      controllability, discriminated between participants as a function of primary and
      comorbid diagnostic status, whereas anxiety sensitivity did not. No relation was
      found between anxiety sensitivity and drug of choice, and relations between
      assessed psychological factors and domains of addiction severity were mixed.
      Findings suggest that heightened bodily sensitivity, emotional avoidance, and
      perceived uncontrollability are common sequelae of patients seeking residential
      substance abuse treatment, but they do not contribute uniquely to drug of choice
      and measures of addiction severity. Theoretical and treatment implications are
      discussed with particular emphasis on approaches that may increase coping with
      untoward bodily cues, decrease avoidance of negative affect, and improve
      patient's sense of personal control over their responses and the environment.

PMID- 12788262
TI  - Assessment of lifetime physical and sexual abuse in treated alcoholics. Validity
      of the Addiction Severity Index.
AB  - We examined the validity of the Addiction Severity Index (ASI) regarding the
      identification of lifetime physical and sexual abuse histories using the
      Structured Trauma Interview (STI) as external criterion in alcohol-dependent
      patients (n=144). Compared to the STI, the ASI showed a lower incidence of
      lifetime physical abuse reports (51% vs. 24%) and lifetime sexual abuse reports
      (29% vs. 17%). Lower incidence of abuse reports was stronger in males compared to
      females, which could be largely explained by ASI perpetrator restrictions (i.e.
      exclusion of several extrafamilial perpetrators). Controlling for these
      restrictions, acceptable sensitivity for both sexual and physical abuse as well
      as good specificity was found. Data indicated no response bias on the ASI in
      terms of social desirability or abuse severity. Sensitivity of the ASI method can
      probably be improved by including an opening preface to the subsequent abuse
      questions, including questions inquiring about abuse histories that have neutral
      wording instead of using the word "abuse," and inclusion of all possible
      perpetrators.

PMID- 12788263
TI  - Evaluating the Lions-Quest "Skills for Adolescence" drug education program.
      Second-year behavior outcomes.
AB  - Thirty-four schools (n=7426 consented sixth graders, 71% of the eligible
      population) were randomized to conditions to test the hypothesis that Skills for
      Adolescence (SFA), a widely used comprehensive life skills training curriculum
      with a dedicated drug education unit, is more effective than standard care in
      deterring and delaying substance use through middle school. Two-year posttest (1
      year post-intervention) data were collected from 5691 eighth graders (77% of
      those who completed the sixth-grade survey and 87% of those who completed the
      seventh-grade survey). Lifetime and recent (last 30 days) use of five substances
      or combinations of substances was compared using mixed-model regression to
      control for school clustering. There were two significant treatment main effects
      at the end of the eighth grade: lifetime (P=.05) and recent (P<.03) marijuana use
      were lower in SFA than control schools with pretest usage and salient demographic
      and psychosocial variables controlled. There was also one significant Treatment x
      Pretest Usage interaction around binge drinking. Baseline binge drinkers in SFA
      schools were less likely to report recent binge drinking than students in control
      schools (P<.01); there were no treatment differences among baseline nonbinge
      drinkers. Analyses of potential mediators of SFA treatment effects on eighth
      grade binge drinking and marijuana use suggested that SFA increased self-efficacy
      around drug refusal skills, but did not affect behavioral intentions, perceptions
      of harm, or perceived peer norms. These 2-year (1-year post-intervention)
      outcomes offer some additional support for SFA effectiveness and the general
      thrust of school-based, life skills-based prevention programs. The promising
      sixth- through eighth-grade findings for SFA, a commercially available program,
      provide a further step in bridging a major gap in the "research to practice"
      literature: theory-based interventions that have documented behavioral effects
      have not enjoyed large-scale implementation, while intuition-based programs that
      have no documented effects still enjoy wide exposure.

PMID- 12788264
TI  - Substance use behaviors among college students with same-sex and opposite-sex
      experience: results from a national study.
AB  - OBJECTIVES: This study seeks to describe the population of college students with
      same-sex sexual experience and determine if these students report more substance
      use than their peers with only opposite-sex experience. METHODS: Questionnaires
      were completed by a national random sample of college students on 119 campuses in
      1999. A total of 10,301 sexually active students were categorized as having only
      opposite-sex, only same-sex, or both-sex partners, and their smoking, binge
      drinking, and marijuana use behaviors were compared. RESULTS: Students who report
      same-sex sexual experiences comprise 6.1% of respondent. Women with both-sex
      partners were approximately twice as likely to smoke, binge drink, and use
      marijuana as women with only opposite-sex partners (OR=1.41-2.78), but women with
      only same-sex partners were not at increased risk for these behaviors. Men with
      both-sex partners were less likely to binge drink (OR=0.54) than men with only
      opposite-sex partners. CONCLUSIONS: Students with same-sex experience are present
      at every type of college. College women with both-sex partners appear to be an
      appropriate target for health interventions; outreach to these students and
      further study of related behaviors are warranted.

PMID- 12788265
TI  - Explaining racial/ethnic differences in smoking during the transition to
      adulthood.
AB  - Using data from a longitudinal panel of nearly 3000 adolescents to predict
      current smoking among young adults, we test whether adding variables that tap
      prior social bonds and influences to the model eliminates race/ethnicity as a
      significant predictor of current smoking. At age 23, African Americans and Asians
      exhibited substantially lower rates of current smoking than Whites and Hispanics.
      Controlling for social influences during high school, particularly exposure to
      siblings and friends who smoked plus parental disapproval of smoking, accounted
      for these differences. Social bonding variables, in contrast, had a limited
      mediating effect. Interventions aimed at decreasing adolescent vulnerability to
      prosmoking influences, reducing overall levels of peer cigarette use, and helping
      parents better convey their disapproval of smoking should help curb young adult
      smoking and diminish racial/ethnic differences in tobacco use.

PMID- 12788266
TI  - Empirical measures vs. perceived gambling severity among youth: why adolescent
      problem gamblers fail to seek treatment.
AB  - A comparison of empirical measures and perceived gambling severity among youth
      was conducted. Participants (N=980), mean age of 18.6 years, completed several
      widely accepted measures of pathological gambling [Diagnostic and Statistical
      Manual of Mental Disorders-IV-Juveniles (DSM-IV-J), South Oaks Gambling Screen
      Revised for Adolescents (SOGS-RA), and Gambler's Anonymous 20 Questions (GA 20)]
      and a questionnaire assessing gambling behavior. Findings revealed that while the
      DSM-IV-J, SOGS-RA, and GA 20 identified between 3.4% and 5.8% of participants as
      probable pathological gamblers, only 1.1% of individuals classified themselves as
      such. Further, 3.3% of the population reported that they considered themselves
      problem gamblers and 66% reported being social gamblers. It appears as though
      either youth are grossly underestimating the severity of their gambling problems
      or the gambling screens are overestimating prevalence rates. The clinical
      implications and future directions for research are considered.

PMID- 12788267
TI  - Alcohol expectancies: integrating cognitive science and psychometric approaches.
AB  - AIMS: To demonstrate an integrative methodology to explore psychological
      constructs, we used multiple methods in the examination of alcohol expectancies-a
      psychological construct that is generally measured using survey methodology. We
      then used the methodology in order to assess the relationship of alcohol
      expectancy dimensions to drinking-related outcomes. DESIGN: We developed alcohol
      expectancy models using a cognitive paradigm designed to maximize cognitive
      activation of expectancies, in order to delineate dimensions of alcohol
      expectancies. Next, using multidimensional scaling (MDS), we defined heuristic
      models representing domains for arousing, sedating, positive, and negative
      alcohol expectancies. We then assessed these models in a separate sample using
      confirmatory factor analysis (CFA) and covariance structure modeling. SETTING:
      The research was conducted at a large public university in the southeastern US.
      PARTICIPANTS: A total of 927 male and female college students ranging in age from
      17 to 35 years participated. MEASUREMENTS: Measures included the Alcohol
      Expectancy Inventory, the Quantity Frequency Index (QFI), and the Drinking Styles
      Questionnaire. FINDINGS: Single indicator models representing expectancies for
      arousing and positive effects of alcohol did not differ significantly in the
      prediction of drinking, and both accounted for significantly more variance in
      self-reported drinking than expectancies for sedating and negative effects of
      alcohol consumption. Expectations for the sedating effects of alcohol accounted
      for significantly more variance than those for negative effects. Expectations for
      sedating effects added unique variance in the prediction of drinking when all
      predictors were simultaneously modeled. CONCLUSIONS: The multiple methods
      integrated here can be used in the development and testing of alcohol expectancy
      models. This integrative methodology warrants further development and validation.

PMID- 12788268
TI  - DUI recidivism: a comparison of Mexican Americans and whites in a northern
      California county.
AB  - OBJECTIVE: While Hispanic offenders for driving under the influence of alcohol
      (DUI) in California are more likely to have a history of multiple offenses
      compared to whites, little is known about characteristics associated with DUI
      recidivism in either ethnic group. Demographic and DUI conviction characteristics
      associated with DUI recidivism are analyzed among Mexican American and white DUI
      offenders in a Northern California county. METHOD: A sample of 459 primarily
      Mexican Americans and 490 whites were randomly selected from records supplied by
      the California Department of Motor Vehicles (DMV) on over 16,000 DUI offenders in
      the county during a 3-year period. DMV data on DUI convictions in the 1- and 5
      year period preceding the identifying DUI offense and the year following the
      identifying offense (the recidivism conviction) were analyzed. RESULTS: Rates of
      recidivism were significantly lower for Mexican Americans (5%) compared to whites
      (11%) who were arrested for DUI but not convicted, but higher for those convicted
      (12% vs. 5%). While conviction status of the identifying DUI offense was not
      predictive of recidivism among Mexican Americans, a DUI conviction in the
      preceding year was significantly predictive. Among white arrestees, receiving a
      conviction was significantly, and negatively, predictive of recidivism, but among
      those who were convicted, a previous DUI conviction in the last year was
      predictive of recidivism. Referral to a DUI treatment program was not a
      significant predictor of recidivism among those convicted in either ethnic group.
      CONCLUSIONS: The data suggest that conviction for a DUI may not play the same
      role in the likelihood of subsequent DUI convictions for Mexican Americans as for
      whites, and this difference may need to be considered in DUI treatment programs.
      Additional research on ethnic differences in DUI offenses and recidivism over
      longer periods of follow-up is needed to determine ethnic-specific intervention
      and prevention strategies for DUI.

PMID- 12788269
TI  - Comparison of DWI offenders with non-DWI individuals on the MMPI-2 and the
      Michigan Alcoholism Screening Test.
AB  - Two groups of driving-while-intoxicated (DWI) offenders with either one DWI
      offense or with repeat offenses were compared to a group of nonoffenders using
      the Minnesota Multiphasic Personality Inventory (MMPI-2) and the Michigan
      Alcoholism Screening Test (MAST). Demographic information was also collected
      regarding their prior legal history, family history, and blood alcohol level at
      the time of the DWI arrest. The results indicated both DWI groups had scored
      significantly higher than the comparison group on the K, Psychopathic Deviate
      (Pd) Scale, Over-Controlled Hostility (O-H) Scale, and MacAndrews Alcoholism
      Scale-Revised (MAC-R). The first offenders and multiple offenders did not differ
      significantly from one another. On the MAST, both DWI offender groups scored
      significantly higher than the nonoffenders. This time, however, the multiple
      offenders scored significantly higher than the first-offender group.
      Unexpectedly, the first offenders and multiple offenders did not differ with
      regards to blood alcohol level at the time of arrest. There were no significant
      differences noted with regard to prior legal history or family history of
      alcoholism for all three groups. These results are discussed with regard to
      assessment implications.

PMID- 12788270
TI  - Interpersonal conflict tactics and substance use among high-risk adolescents.
AB  - Adolescents who use aggressive tactics to handle interpersonal conflicts may be
      at high risk for substance use, while adolescents who possess coping strategies
      to avoid or manage interpersonal conflict may be at lower risk for substance use.
      This study examined the association between interpersonal conflict tactics and
      substance use among 631 continuation high school students. Items from a modified
      Conflict Tactics Scale formed three factors: Physical Aggression, Nonphysical
      Aggression, and Nonaggression. Logistic regression analyses revealed that
      adolescents' ways of responding to interpersonal conflicts were associated with
      their substance use. Use of physical aggression was associated with a higher risk
      of cigarette, alcohol, marijuana, and other drug use. Use of nonphysical
      aggression was associated with a higher risk of cigarette and alcohol use. Use of
      nonaggressive conflict tactics was associated with a lower risk of cigarette use.
      Adolescents who respond to interpersonal conflicts in an aggressive manner,
      whether physical or verbal/psychological, may be at increased risk for substance
      use, while nonaggressive conflict management skills may be protective. Possibly,
      teaching adolescents nonaggressive techniques for handling interpersonal conflict
      may be a useful strategy for preventing both interpersonal violence and substance
      use.

PMID- 12788271
TI  - Increasing the efficacy of cue exposure treatment in preventing relapse of
      addictive behavior.
AB  - Theoretically, cue exposure treatment should be able to prevent relapse by
      extinguishing conditioned drug responding (e.g. cue-elicited craving). According
      to contemporary learning theory, though, extinction does not eliminate
      conditioned responding. Analogous cue exposure with response prevention (CERP) as
      a treatment of addictive behavior might not eliminate the learned relation
      between drug-related cues and drug use. This does not necessarily mean that cue
      exposure cannot successfully prevent relapse. Various suggestions for increasing
      the efficacy of cue exposure treatment are being discussed from a contemporary
      learning theory perspective. It is suggested that cue exposure treatment
      incorporating retrieval cues can be a beneficial treatment in preventing relapse
      of addictive behavior.

PMID- 12788272
TI  - Measuring therapeutic attitude among drug workers.
AB  - A reluctance of nonspecialists to work with drug and alcohol misusers have
      focused upon belief-based systems, including therapeutic commitment (TC) and
      situation-specific constraints. This paper describes the development and
      assessment of a theoretical model for nonspecialist drug workers, characterised
      as a synthesis of attitudinal and constraints explanations. A cohort of 189
      nonspecialist drug workers completed self-report measures of overall TC and
      situational constraints scales. Predictive analysis of associations between TC,
      role security (RS), role requirements, and situational constraints was performed
      to explore direct and indirect effects. Such assessment allowed for the
      identification of a predictive process by which TC may be established,
      manipulated, and maintained. Levels of TC were found to be explained by the
      direct effects of self-esteem (SE), situational constraints, role support, and
      RS. Role support and situational constraints were also found to have indirect
      effects. Experience with working with drug users and education on drug-related
      issues were found to have predominantly indirect effects on TC via situational
      constraints and RS. Findings show the synthesised model to be partially
      supported. Implications for the development of a process-driven theoretical
      understanding of TC and situational constraints are discussed, and applied
      recommendations for training intervention are presented.

PMID- 12788273
TI  - Predictors of change in binge drinking over a 3-month period.
AB  - Self-efficacy and positive and negative alcohol expectancies have been associated
      with drinking reduction for some groups, but the relationship of these constructs
      with changes in high-risk binge drinking behavior among young adults over time is
      poorly understood. Seventy-six young adults between the ages of 18-32 were
      recruited to examine this question. Lower self-efficacy and greater positive
      alcohol expectancies predicted greater numbers of follow-up binge drinking
      episodes, and greater positive alcohol expectancies predicted greater follow-up
      alcohol consumption. Young adults with lower self-efficacy, and greater numbers
      of positive alcohol expectancies may be at risk for experiencing a worsening
      binge pattern over time.

PMID- 12788275
TI  - Regulation of Bt crops in Canada.
AB  - The Canadian Food Inspection Agency (CFIA) regulates environmental releases of
      plants with novel traits, which include transgenic plants such as Bt crops. Bt
      crops are regulated in Canada because they express insect resistance novel to
      their species. Commercialization of crops with novel traits such as the
      production of insecticidal Bt proteins requires an approval for environmental
      release, as well as approvals for use as feed and food. Environmental factors
      such as potential impacts on non-target species are considered. Insect resistance
      management (IRM) may be imposed as a condition for environmental release of Bt
      crops to delay the development of resistance in the target insect. Bt potato and
      European corn borer-resistant Bt corn have been released with mandatory IRM. The
      CFIA imposes an IRM plan consisting of appropriate refugia, education of farmers
      and seed dealers, and monitoring and mitigation. Industry, regulators, government
      extension staff and public researchers provide expert advice on IRM.

PMID- 12788276
TI  - Legal and regulatory concerns about transgenic plants in Brazil.
AB  - Brazil has a biosafety law that was approved in 1995. This law provides for a
      horizontal type of regulation that coordinates other existing regulatory
      frameworks in the areas of agriculture, health and environment. Various federal
      government departments are responsible for implementing the law. The National
      Technical Biosafety Commission is the national competent authority on biosafety
      with overall responsibility. In the case of Bt plants or any insecticidal
      organism, the Agrochemical Law also applies and authorization for laboratory,
      greenhouse and field studies must be obtained from the Plant Protection
      Secretariat, the Brazilian Institute of Environment and the National Agency of
      Health. Furthermore, the National Environmental Council must issue a license for
      commercialization of any GMO. There is pressure needed for capacity building and
      to harmonize the regulatory and administrative frameworks among the different
      federal departments involved. Some perspectives and challenges for the commercial
      registration of transgenic crops are discussed.

PMID- 12788277
TI  - Brazil and the development of international scientific biosafety testing
      guidelines for transgenic crops.
AB  - Under the umbrella of the International Organisation of Biological Control
      (IOBC), an international working group of public sector scientists entitled on
      "Transgenic Organisms in Integrated Pest Management and Biological Control" has
      been organized. The group will develop scientific principles and detailed
      scientific guidelines for biosafety testing of transgenic crops. The key elements
      of this project are: (1) An international initiative including expert scientists
      from leading research institutions in developed and developing countries; (2)
      coordination of the development and implementation of the guidelines as a dynamic
      process, which will include scientific and technical capacity building and
      communication among scientists and between scientists and policy makers; (3)
      rapid serial publication of sections of the guidelines as they are completed; and
      (4) rapid and timely revision of previously published sections. The guidelines
      will be constructed on a case-by-case basis and will have no regulatory
      legitimacy themselves.

PMID- 12788278
TI  - Regulatory and associated political issues with respect to Bt transgenic maize in
      the European union.
AB  - Legislation at the national level in Europe as well as that developed by the
      European Union (EU) generally permits release and commercialization of
      genetically modified organisms (GMOs). However, only 10 plant/event combinations
      were registered as of 2002: three maize events (Bt176, Mon810, and Bt11), with
      the other seven divided among carnation (3), oil-seed rape (2), tobacco (1), and
      raddiccio (1). Of these, only one maize event (Bt176) has been registered as a
      legal variety, and this was in Spain, where 22,000ha have been planted annually
      since 1998. In this paper, we first provide an overview on the complexity of EU
      GMO legislation. Then we discuss the minor role that results of EU-funded
      biosafety research have had on governmental policy. Finally, we provide
      information about initiatives for post-commercialization monitoring plans of Bt
      maize in Europe. As a result of the slow progress to date, we conclude that
      commercialization of GMOs will be seriously delayed in the EU for the next
      several years.

PMID- 12788279
TI  - Considerations for conducting research in agricultural biotechnology.
AB  - Science has shown its increased vulnerability because of two recent high-profile
      articles published in major journals on corn produced through biotechnology: a
      laboratory report suggesting profound consequences to monarch butterfly
      populations due to Bt corn pollen and a report suggesting transgenic
      introgression into Mexican maize. While both studies have been widely regarded as
      having flawed methodology, publishing these studies has created great
      consternation in the scientific community, regulatory agencies and the general
      public. There are roles and responsibilities of scientists, scientific journals,
      the public media, public agencies, and those who oppose or advocate a specific
      technology, and serious consequences when those roles and responsibilities go
      awry. Modern communication may exacerbate the flow of misinformation and easily
      lead to a decline in public confidence about biotechnology and science. However,
      common sense tells us that scientific inquiry and the publication and reporting
      of results should be performed with high standards of ethical behavior,
      regardless of one's personal perspective on agricultural biotechnology.

PMID- 12788280
TI  - Precautionary risk assessment of Bt maize: what uncertainties?
AB  - GM crops have become a test case for the conflicting slogans of 'the
      precautionary principle' versus 'sound science.' The issues can be illustrated by
      developments in regulatory science for Bt maize in the European Union. As this
      case study suggests, risk assessment is always framed by some account of the
      relevant uncertainties. These in turn depend upon how the environment is valued
      and how scientific questions are posed about cause-effect pathways of potential
      harm. The slogan of 'sound science' hides such judgements, by representing
      ignorance or value-judgements as 'science.' By contrast, precaution can challenge
      such judgements, identify new unknowns, generate different criteria for evidence,
      open up new scientific questions, and make these judgements more transparent. It
      is doubtful whether these complexities have been fully acknowledged by
      specialists, and thus whether the continued risk debate is due solely to a public
      misunderstanding of science.

PMID- 12788281
TI  - Interaction of microbial populations in Steinernema (Steinernematidae, Nematoda)
      infected Galleria mellonella larvae.
AB  - Infection of Galleria mellonella larvae with the entomopathogenic nematodes
      Steinernema feltiae (A21 and R strains) and Steinernema glaseri (Dongrae)
      resulted in several species of bacteria, including the respective bacterial
      symbiont, Xenorhabdus spp., growing in the infected insect cadavers. These other
      bacteria were Enterococcus in all three nematode infections studied and
      Acinetobacter in the S. feltiae infections. The respective populations of these
      bacteria changed with time. Following infection of G. mellonella larvae with any
      one of the Steinernema sp., only Enterococcus bacteria were detected initially in
      the dead larvae. Between 30 and 50h post-infection Xenorhabdus bacteria were
      detected and concurrent with this Enterococcus population declined to zero. This
      was probably due to secondary metabolites with antibacterial properties that were
      produced by Xenorhabdus. In the S. feltiae (both R and A21 strains) infections a
      third bacterium, Acinetobacter, appeared at about 130h (in S. feltiae A21
      infections) or 100h (in S. feltiae R infections) and increased in population size
      to approximately that of Xenorhabdus. It was demonstrated that Enterococcus,
      orginating from the G. mellonella digestive tract, was sensitive to the
      organically soluble antimicrobials produced by Xenorhabdus but Acinetobacter,
      which was carried by the nematode, was not.

PMID- 12788282
TI  - Starvation induced stress and the susceptibility of the Colorado potato beetle,
      Leptinotarsa decemlineata, to infection by Beauveria bassiana.
AB  - Starvation of second instar Colorado potato beetle larvae for 24h immediately
      after treatment with Beauveria bassiana conidia increased susceptibility to the
      pathogen and subsequent sporulation of cadavers but decreased time to larval
      death. In feeding studies, B. bassiana-treatment had no effect on subsequent
      larval development, and mortality occurred 5-6 days after treatment. Twenty-four
      hours of starvation alone retarded subsequent larval development but did not
      affect mortality. Mortality of B. bassiana-treated starvation stressed larvae
      occurred 4-5 days after treatment. Both B. bassiana treatment and 24h starvation
      significantly reduced total foliage consumption and daily weight gains. On the
      day of treatment, B. bassiana had no effect on the efficiency with which food was
      converted to biomass (ECI). ECI was not affected by B. bassiana or starvation
      alone on the day following treatment but was significantly affected by a
      combination of both. When larvae were exposed to a range of limited food
      quantities, ECI decreased with decreasing food availability but only extreme
      stress (starvation for 24h) increased susceptibility to B. bassiana. Topical
      application of Dacryodes excelsa resin (an antifeedant) to potato leaves caused a
      concentration dependent reduction in foliage consumption and weight gain by
      second instar larvae but did not affect larval mortality. When larvae were
      exposed to a fixed concentration of B. bassiana and a range of antifeedant
      concentrations there were significant linear relationships between 24h larval
      weight gain and mortality and 24h larval weight gain and sporulation. The
      interaction between starvation stress and the susceptibility to B. bassiana
      infection is discussed and its possible implications in pest management
      considered.

PMID- 12788283
TI  - Ecological characterization of Steinernema scarabaei, a scarab-adapted
      entomopathogenic nematode from New Jersey.
AB  - This study describes the basic ecological characteristics of the entomopathogenic
      nematode Steinernema scarabaei (Rhabditida: Steinernematidae) that was originally
      isolated from epizootics in scarab populations in New Jersey turfgrass areas.
      Under laboratory conditions, S. scarabaei infected a limited range of insect
      species and appeared best adapted to scarab larvae as hosts. It uses a widely
      ranging foraging strategy with a low attachment rate to mobile hosts on the soil
      surface but with excellent infection of sedentary host placed at >or=2 cm soil
      depth. It has a wide thermal activity range with optimum infectivity from 17.5 to
      25 degrees C. Because of its foraging strategy and adaptation to scarab larvae as
      hosts, S. scarabaei has outstanding potential for the control of scarab pests.

PMID- 12788284
TI  - Vibrio lentus associated with diseased wild octopus (Octopus vulgaris).
AB  - Studies were undertaken to identify the bacteria involved in a disease of wild
      octopus (Octopus vulgaris). Signs of the disease include round hard lesions in
      the arms or head mantle, leading, in advanced cases, to the loss of skin and the
      exposure of the muscle beneath. Bacterial strains isolated from sterile organs
      have been evaluated taxonomically and by experimental infections. Different
      phenotypes and ribotypes of Vibrio lentus were identified. Experimental infection
      by bath challenge demonstrated that V. lentus was able to reproduce the skin
      lesions, colonize the internal organs and induce mortality in healthy octopuses.
      V. lentus was re-isolated from the skin lesions and gill heart of dead octopuses,
      as confirmed by numerical taxonomy analysis. No effects were produced in sea
      bream or turbot by intraperitoneal injection of the bacterial isolate.

PMID- 12788285
TI  - Effect of soil temperature and moisture on survival and infectivity of
      Metarhizium anisopliae to four tephritid fruit fly puparia.
AB  - The infectivity of 4 isolates of Metarhizium anisopliae to puparia of Ceratitis
      capitata treated as late third-instar larvae in unsterilized soil was
      investigated in the laboratory under controlled temperature and moisture. At 20
      30 degrees C, mortality in puparia was highest at water potential of -0.1 and 
      0.01 mega Pascal (MPa) and lowest at water potential of -0.0055 and -0.0035 MPa
      in all the isolates. In wetter soil however, isolates ICIPE 20 and 60 caused
      significantly higher mortality than ICIPE 18 and 69. The survival of conidia in
      drier soil (-0.1 MPa) was not adversely affected at all temperatures. However, in
      wet soil (-0.0035 MPa) there was drastic reduction in colony counts in ICIPE 18
      and 69 at 25 and 30 degrees C but conidial density in ICIPE 20 and 60 remained at
      the initial level at 14 days after inoculation at all temperatures. When ICIPE 20
      was evaluated against three other fruit fly species (Ceratitis cosyra, Ceratitis
      rosa, and Ceratitis fasciventris), significant reduction in adult emergence and
      higher pupal mortality occurred in C. cosyra and C. fasciventris than in C. rosa
      at a combination of 15 and 20 degrees C and -0.1 and -0.0035 MPa. However, at
      higher temperature and the same moisture level, the isolates were equally
      pathogenic across the 3 species. It is probable that in addition to pathogen
      cycling and multiplication from dead infected insects in the soil, a balance
      between microbial degradation and replenishment of inoculum of virulent isolates
      occur through fluctuations in, and intricate interactions between temperature and
      moisture levels. This study is indicative of the potential of using isolate ICIPE
      20 for soil inoculation against pupariating third-instar larva of fruit flies,
      thus providing a novel alternative to chemical soil application.

PMID- 12788286
TI  - A model of Taura syndrome virus (TSV) epidemics in Litopenaeus vannamei.
AB  - Taura syndrome virus (TSV) is a highly virulent pathogen of Litopenaeus vannamei,
      has affected shrimp aquaculture throughout the world, and threatens wild
      populations. Despite its importance, little work has been done on the pathogen's
      formal epidemiology. Therefore we developed a compartment model for epidemics of
      TSV in closed populations of L. vannamei. The model includes five compartments,
      uninfected susceptible, prepatently infected, acutely infected, chronically
      infected, and dead infected shrimp. The transmission coefficients, patency
      coefficient, virulence coefficients, and removal coefficient (disappearance of
      dead infected shrimp) control the dynamics of the model. We estimated the
      coefficients in laboratory studies and inserted the estimates in the model to
      characterize TSV epidemics and to estimate the basic reproduction ratio R(0) and
      threshold density for TSV epidemics in L. vannamei. Further we examined through
      computer simulation the effect of varying the coefficients on R(0). Decreases in
      transmission decrease R(0), decreases in virulence increase R(0), increases in
      patency do not affect R(0), and increases in recovery most likely increase R(0)
      but under some conditions might decrease it.

PMID- 12788287
TI  - Ultrastructural characterization and further transmission studies of Thelohania
      solenopsae from Solenopsis invicta pupae.

PMID- 12788288
TI  - Culex nigripalpus nucleopolyhedrovirus (CuniNPV) infections in adult mosquitoes
      and possible mechanisms for dispersal.

PMID- 12788289
TI  - The use of low-frequency vocalizations in African elephant(Loxodonta africana)
      reproductive strategies.
AB  - Fertility-advertisement calls in females are predicted to occur in nonmonogamous
      species where males and females are widely separated in space. In African
      elephants, low-frequency vocalizations have thus been suggested as a reproductive
      strategy used by fertile females to attract mates. This study examined the use of
      low-frequency vocalizations with respect to different phases of the estrous cycle
      in African elephants by simultaneously monitoring vocalizations, behavior, and
      hormonal profiles. Subjects were one male and six female African elephants housed
      at Disney's Animal Kingdom. No acoustically distinct vocalizations were
      restricted to the ovulatory follicular phase. However, overall rate of low
      frequency vocalization as well as the rate of one acoustically distinct
      vocalization changed over the estrous cycle, with highest rates of calling
      related to the first period of follicular growth, or anovulatory follicular
      phase. Elevated rates of vocalization thus were not restricted to behavioral
      estrus and occurred much earlier in the estrous cycle than in most species that
      produce fertility-advertisement calls. Both herd composition and elephant
      identity also affected rates of vocalization. Vocalizations therefore may not be
      reliable signals of actual fertility. However, the increase in vocalizations in
      advance of estrus may attract males to the herd prior to ovulation, facilitating
      both male-male competition and female choice. Once present in the herd, males may
      then switch strategies to use more reliable chemical and visual cues to detect
      ovulating females.

PMID- 12788291
TI  - The display of sexual behaviors by female rats administered ICI 182,780.
AB  - ICI 182,780 (ICI) is a pure antiestrogen that when administered systemically does
      not cross the blood-brain barrier, thus its actions are limited to the periphery.
      Four experiments were conducted to test the effects of ICI on the display of
      sexual behaviors in ovariectomized rats. Experiment 1 examined the effects of
      three doses of ICI (250, 500, and 750 micro g/rat) on sexual receptivity and
      paced mating behavior in rats primed with estradiol benzoate (EB) in combination
      with progesterone (P). Experiments 2 and 3 compared the display of sexual
      behaviors in rats primed with EB+P or EB alone and administered either 250 micro
      g ICI (Experiment 2) or 500 micro g ICI (Experiment 3). Experiment 4 tested the
      effects of ICI (250 and 500 micro g) on the expression of estrogen-induced
      progestin receptors in the uterus. ICI did not affect the display of sexual
      receptivity in any experiment. In rats primed with EB+P, paced mating behavior
      was altered by the 500 and 750 micro g, but not the 250 micro g, doses of ICI.
      The lowest (250 micro g) dose of ICI did alter paced mating behavior in rats
      primed with EB alone. The effects of ICI on paced mating behavior were manifested
      by a substantial lengthening of contact-return latencies following intromissions
      and ejaculations. The percentage of exits were not affected by ICI. Estrogen
      stimulation of uterine weight and induction of uterine progestin receptors was
      suppressed by ICI (250 and 500 micro g). ICI effects on paced mating behavior in
      hormone-primed female rats are likely to reflect antiestrogenic actions in the
      periphery, including interference with the estrogen induction of progestin
      receptors.

PMID- 12788290
TI  - Response of ERalpha-IR and ERbeta-IR cells in the forebrain of female rats to
      mating stimuli.
AB  - Sexual behavior in female rats depends on the action of estradiol on estrogen
      receptors (ERs) found in particular brain regions. While hormonal regulation of
      female sexual behavior requires ERalpha, the possible functions of ERbeta remain
      to be clarified. Mating stimulation has several behavioral and physiological
      consequences and induces Fos expression in many brain areas involved in the
      regulation of reproductive behavior and physiology. In addition, some cells in
      which mating induces Fos expression coexpress ERalpha. To determine whether cells
      in which Fos is induced by a particular mating stimulus coexpress ERalpha,
      ERbeta, or both, we used a triple-label immunofluorescent technique to visualize
      ERalpha-, ERbeta-, and mating-induced Fos-immunoreactivity (Fos-ir) in neurons in
      which mating stimulation reliably increases Fos expression. Ovariectomized,
      hormone-primed rats were either unmated, received 15 mounts, or received 15
      intromissions. In the rostral medial preoptic area, Fos-ir was induced by mounts
      alone primarily in cells coexpressing ERalpha-ir, while Fos-ir was induced by
      intromissions mainly in cells coexpressing both ERalpha-ir and ERbeta-ir
      (ERalpha/ERbeta-ir). In the dorsal part of the posterodorsal medial amygdala, Fos
      ir was induced by intromissions in cells coexpressing ERalpha-ir and
      ERalpha/ERbeta-ir. However, in the ventral part of the posterodorsal medial
      amygdala, Fos-ir was induced by intromissions primarily in cells coexpressing
      only ERbeta-ir. These data suggest that qualitatively different sexual stimuli
      may be integrated through distinct ER-containing circuits in the rostral medial
      preoptic area and posterodorsal medial amygdala. The diversity in coexpression of
      type of ER in cells in different brain areas after various mating stimuli
      suggests a role for both ERalpha and ERbeta in the integration of hormonal
      information and information related to mating stimuli.

PMID- 12788292
TI  - The conference on reproductive behavior: a history.
AB  - The Society for Behavioral Neuroendocrinology was, in part, an outgrowth of the
      Conference on Reproductive Behavior, which was, in turn, an outgrowth of the West
      Coast Sex Meetings. In this article I trace the history of these organizations.
      The West Coast meetings provided an opportunity for free and informal exchange
      among west coast researchers studying sexual behavior. The 29 meetings of the
      Conference on Reproductive Behavior began with a similar format that evolved as
      success and growth forced numerous changes. With time, the meetings became more
      structured and more dependent on time limits, and added invited addresses,
      symposia, workshops, roundtables, posters, tours, and papers presented by
      abstract only. The administrative structure was kept as simple as possible. With
      changing times, these informal meetings eventually were superseded by the Society
      for Behavioral Neuroendocrinology.

PMID- 12788293
TI  - Social status does not predict corticosteroid levels in postdispersal male
      spotted hyenas.
AB  - In social species with low rates of direct male competition levels of
      corticosteroids should not correlate with social status. Male spotted hyenas
      acquire social status by observing strict queuing conventions over many years,
      and thus levels of male-male aggression are low, and male social status and
      tenure are closely correlated. In this study, we investigated whether the low
      rate of direct male competition in spotted hyenas was reflected in fecal
      corticosteroid levels of adult males in the Serengeti National Park. Also,
      interactions with dominant females may influence corticosteroid levels of males,
      and it has been suggested recently that males with a long tenure (high rank) are
      more stressed by females than males with a short tenure (low rank). We tested
      whether there is a difference in the likelihood of being aggressively challenged
      by dominant females between long-tenured and short-tenured males. Short-tenured
      males were more likely to elicit an aggressive response by females than long
      tenured males, but previous work suggests that they also interacted less
      frequently with females, thus avoiding putting themselves in a potentially
      stressful situation. Thus, as expected, the comparison of males in three
      different clans revealed no correlation between social status or tenure and fecal
      corticosteroid levels. However, males of the largest clan had the highest levels
      of fecal corticosteroids, possibly reflecting higher rates of social interactions
      in larger clans.

PMID- 12788294
TI  - Plasma corticosterone in American kestrel siblings: effects of age, hatching
      order, and hatching asynchrony.
AB  - Although it is well documented that hatching asynchrony in birds can lead to
      competitive and developmental hierarchies, potentially greatly affecting growth
      and survival of nestlings, hatching asynchrony may also precipitate modulations
      in neuroendocrine development or function. Here we examine sibling variation in
      adrenocortical function in postnatally developing, asynchronously hatching
      American kestrels (Falco sparverius) by measurements of baseline and stress
      induced levels of corticosterone at ages 10, 16, 22, and 28 days posthatching.
      There was a significant effect of hatching order on both baseline and stress
      induced corticosterone levels during development and these effects grew stronger
      through development. First-hatched chicks exhibited higher baseline levels than
      later-hatched chicks throughout development and higher stress-induced levels
      during the latter half of development. Furthermore, there was significant
      hatching span (difference in days between first- and last-hatched chicks) x
      hatching order interaction on both baseline and stress-induced corticosterone
      levels during development. Hatching span was also positively correlated with both
      measures of corticosterone and body mass in first-hatched chicks, but was
      negatively correlated with these factors through most of the development in last
      hatched chicks. It is known that hatching asynchrony creates mass and size
      hierarchies within kestrel broods and we suggest that hierarchies in
      adrenocortical function among siblings may be one physiological mechanism by
      which these competitive hierarchies are maintained.

PMID- 12788295
TI  - Are corticosterone levels a good indicator of food availability and reproductive
      performance in a kittiwake colony?
AB  - We evaluated the use of corticosterone to gauge forage availability and predict
      reproductive performance in black-legged kittiwakes (Rissa tridactyla) breeding
      in Alaska during 1999 and 2000. We modeled the relationship between baseline
      levels of corticosterone and a suite of individual and temporal characteristics
      of the sampled birds. We also provided supplemental food to a sample of pairs and
      compared their corticosterone levels with that of pairs that were not fed.
      Corticosterone levels were a good predictor of forage availability in some
      situations, although inconsistencies between corticosterone levels and
      reproductive performance of fed and unfed kittiwakes suggested that this was not
      always the case. In general, higher corticosterone levels were found in birds
      that lacked breeding experience and in birds sampled shortly after arriving from
      their wintering grounds. All parameters investigated, however, explained only a
      small proportion of the variance in corticosterone levels. We also investigated
      whether corticosterone, supplemental feeding, year of the study, breeding
      experience, body weight, and sex of a bird were able to predict laying, hatching,
      and fledging success in kittiwakes. Here, breeding experience, year of the study,
      and body weight were the best predictors of a bird's performance. Corticosterone
      level and supplemental feeding were good predictors of kittiwake reproductive
      performance in some cases. For example, corticosterone levels of birds sampled
      during the arrival stage reliably predicted laying success, but were less
      reliable at predicting hatching and fledging success. Counts of active nests with
      eggs or chicks may be more reliable estimates of the actual productivity of the
      colony. Supplemental feeding had strong effects on kittiwake productivity when
      natural forage was poor, but had little effect when natural forage was plentiful.

PMID- 12788296
TI  - Female rats develop conditioned place preferences for sex at their preferred
      interval.
AB  - Female rats engage in approach and avoidance behaviors directed toward the male
      to "pace" the rate of copulation. These pacing behaviors result in a pattern of
      vaginocervical stimulation that triggers a neuroendocrine reflex that is
      important for pregnancy to result from insemination. Each female rat has a
      preferred pacing interval, and females develop conditioned place preferences for
      paced sex versus nonpaced sex. Research from this laboratory has reported that
      extracellular dopamine concentrations in striatum and nucleus accumbens are
      greater in female rats that are engaging in paced sex compared with those
      engaging in nonpaced sex. Furthermore, females who have males removed at their
      preferred intervals during a copulatory bout show extracellular dopamine
      concentrations comparable to females engaging in paced sex. It is unclear,
      however, whether they would also develop a conditioned place preference for sex
      under such conditions. This experiment was designed to address this question.
      Female rats had six exposures each to a chamber in which they engaged in nonpaced
      sex and a chamber in which they engaged in paced or preferred pacing interval
      sex. Following conditioning trials, females were tested for a conditioned place
      preference. The findings indicate that female rats develop conditioned place
      preferences for paced sex and for sex in which the male is removed at her
      preferred interval. This suggests that sexual behavior is reinforcing to female
      rats when their preferred interval is achieved, whether or not they are actively
      controlling the rate of copulation.

PMID- 12788297
TI  - Comparative analysis of male androgen responsiveness to social environment in
      birds: the effects of mating system and paternal incubation.
AB  - Male androgen responses to social challenges have been predicted to vary with
      mating system, male-male aggressiveness, and the degree of paternal investment in
      birds ("challenge hypothesis," Am. Nat. 136 (1990), 829). This study focused on
      the interspecific predictions of the challenge hypothesis. Comparative methods
      were used to control for effects of the phylogenetic relatedness among the
      sampled species. Male androgen data of 84 bird species were collected from
      literature records on seasonal androgen patterns. From these, the androgen
      responsiveness (AR) was calculated as described in the original challenge
      hypothesis (i.e., maximum physiological level/breeding baseline). Scatterplots of
      AR versus mating strategy, male-male aggressiveness, and the degree of paternal
      care confirmed the expected interspecific patterns. When phylogenetic analyses
      were performed among all of the sampled species, the effects of paternal
      investment disappeared while the AR remained covarying to a high degree with
      mating system and male-male aggressiveness. Although these mechanisms may be
      different at the intraspecific level, this suggests that interspecific
      differences of AR in male birds may have evolved in response to changes of mating
      strategies, rather than in response to altered paternal duties. However, control
      for phylogeny among the subsample of 32 passerine species revealed that if any
      paternal investment contributed to the observed variance in AR, then the change
      from "no male incubation" to "male shares incubation duties" represented the most
      effective, whereas the male's contribution to feeding offspring did not explain
      the observed variation of AR.

PMID- 12788298
TI  - Pacing in heart failure: patient and pacing mode selection.

PMID- 12788299
TI  - Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE
      project.
AB  - AIMS: The SCORE project was initiated to develop a risk scoring system for use in
      the clinical management of cardiovascular risk in European clinical practice.
      METHODS AND RESULTS: The project assembled a pool of datasets from 12 European
      cohort studies, mainly carried out in general population settings. There were
      20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person
      years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were
      deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease
      was calculated using a Weibull model in which age was used as a measure of
      exposure time to risk rather than as a risk factor. Separate estimation equations
      were calculated for coronary heart disease and for non-coronary cardiovascular
      disease. These were calculated for high-risk and low-risk regions of Europe. Two
      parallel estimation models were developed, one based on total cholesterol and the
      other on total cholesterol/HDL cholesterol ratio. The risk estimations are
      displayed graphically in simple risk charts. Predictive value of the risk charts
      was examined by applying them to persons aged 45-64; areas under ROC curves
      ranged from 0.71 to 0.84. CONCLUSIONS: The SCORE risk estimation system offers
      direct estimation of total fatal cardiovascular risk in a format suited to the
      constraints of clinical practice.

PMID- 12788300
TI  - Long-term tracking of cardiovascular risk factors among men and women in a large
      population-based health system: the Vorarlberg Health Monitoring & Promotion
      Programme.
AB  - AIMS: To document tracking patterns, if any, over time, of classical
      cardiovascular risk factors in men and women participants in the Vorarlberg
      Health Monitoring and Promotion Programme (VHM&PP) METHODS AND RESULTS: 67,413
      men and 82,237 women underwent a total of 45,4448 standardised examinations in
      the 15 year period 1985-1999. Measures included were systolic and diastolic blood
      pressure, height, weight and fasting sample for total cholesterol, triglycerides,
      gamma-gt and blood glucose. Tracking coefficients were calculated by
      multivariable regression models using the GEE estimation method. All variables
      showed evidence of significant tracking over time, whether estimated in 10-year
      age bands or among individuals categorized as being at high risk using cut-points
      proposed by international guidelines. Effects were most marked for body mass
      index (0.87, SE0.005 in men and 0.89, SE0.003 in women), and were also associated
      with increasing age. Women who died during follow-up showed stronger tracking
      patterns for triglycerides and gamma-gt and weaker effects for blood pressure,
      but there was no effect on patterns according to survival in men. Tracking
      coefficients were weaker among initially high-risk individuals. CONCLUSIONS: This
      is the largest study yet of adults to demonstrate significant tracking effects of
      cardiovascular risk factors over time. The strength of this effect should be
      considered in assessing effectiveness of risk factor modification programmes. The
      study is novel too in highlighting more fully differences according to gender and
      social circumstances and in taking account of the impact on long-term survival.

PMID- 12788301
TI  - Nurse-led heart failure clinics improve survival and self-care behaviour in
      patients with heart failure: results from a prospective, randomised trial.
AB  - AIM: The aim of this trial was to prospectively evaluate the effect of follow-up
      at a nurse-led heart failure clinic on mortality, morbidity and self-care
      behaviour for patients hospitalised due to heart failure for 12 months after
      discharge. METHODS: A total of 106 patients were randomly assigned to either
      follow-up at a nurse-led heart failure clinic or to usual care. The nurse-led
      heart failure clinic was staffed by specially educated and experienced cardiac
      nurses, delegated the responsibility for making protocol-led changes in
      medications. The first follow-up visit was 2-3 weeks after discharge. During the
      visit the nurse evaluated the heart failure status and the treatment, gave
      education about heart failure and social support to the patient and his family.
      RESULTS: There were fewer patients with events (death or admission) after 12
      months in the intervention group compared to the control group (29 vs 40, p=0.03)
      and fewer deaths after 12 months (7 vs 20, p=0.005). The intervention group had
      fewer admissions (33 vs 56, p=0.047) and days in hospital (350 vs 592, p=0.045)
      during the first 3 months. After 12 months the intervention was associated with a
      55% decrease in admissions/patient/month (0.18 vs 0.40, p=0.06) and fewer days in
      hospital/patient/month (1.4 vs 3.9, p=0.02). The intervention group had
      significantly higher self-care scores at 3 and 12 months compared to the control
      group (p=0.02 and p=0.01). CONCLUSIONS: Follow up after hospitalisation at a
      nurse-led heart failure clinic can improve survival and self-care behaviour in
      patients with heart failure as well as reduce the number of events, readmissions
      and days in hospital.

PMID- 12788302
TI  - The impact of gender on the treatment and outcomes of patients with early
      reinfarction after fibrinolysis: insights from ASSENT-2.
AB  - AIMS: To assess gender differences in patients with early reinfarction after
      fibrinolysis for acute myocardial infarction (AMI) and the impact of these
      differences on treatment and outcomes. METHODS AND RESULTS: We studied 3.7% of
      men (n=481) and 4.8% of women (n=189) with early reinfarction after fibrinolysis
      for AMI in the ASSENT-2 trial of 16,949 patients. Women with reinfarction were
      older and more often had hypertension, diabetes, and major bleeding prior to
      reinfarction. Despite adjustment for these differences, women with reinfarction
      were less likely to receive repeat fibrinolytic therapy (OR: 0.55; 95% CI: 0.37
      0.84). Aggressive treatment by either repeat fibrinolysis or urgent
      revascularization was associated with reduced 1-year mortality irrespective of
      gender. Death within 24 h of reinfarction was more frequent in women and
      accounted for a greater proportion of their 1-year mortality (56.0 vs 34.8%;
      p=0.02). The excess mortality in women at 1 year (27.3 vs 19.9%; p=0.045) was
      eliminated after adjustment for gender differences in baseline risk profile.
      CONCLUSION: Women with early reinfarction following fibrinolysis for AMI had more
      frequent early death and were managed less aggressively. These findings suggest
      the need for increased awareness and timely intervention in these patients.

PMID- 12788303
TI  - Up-regulation of IL-18BP, but not IL-18 mRNA in rat liver by LPS.
AB  - Interleukin (IL)-18 is a pro-inflammatory cytokine that plays a critical role in
      inflammation leading to liver damage, through promotion of Fas-mediated
      apoptosis. Inhibition of IL-18 activity protects against LPS-induced lethality in
      mice and against liver damage induced by LPS after sensitisation of mice with
      Proprionibacterium acnes. A specific, potent, endogenous inhibitor of IL-18 (IL
      18BP) has been identified in mice and humans, and IL-18BP mRNA is expressed
      constitutively in liver. The objectives of this study were to compare changes in
      IL-1beta and IL-18 mRNA expression in the liver of rats in response to peripheral
      injection of LPS, using real-time PCR, and also to investigate whether IL-18BP
      mRNA expression is affected by this treatment. LPS rapidly up-regulated IL-1beta
      mRNA expression, but IL-18 mRNA expression was unaffected by LPS treatment.
      Unlike IL-18, IL-18BP mRNA was up-regulated dramatically by approximately 12-fold
      above nai;ve levels, peaking 3 h after LPS injection. This ability of LPS to up
      regulate expression of the endogenous IL-18 inhibitor may indicate a mechanism by
      which the inflammatory response to LPS is regulated.

PMID- 12788304
TI  - Lack of association between pro-inflammatory genotypes of the interleukin-1 (IL
      1B -31 C/+ and IL-1RN *2/*2) and gastric cancer/duodenal ulcer in Korean
      population.
AB  - IL-1beta is a pro-inflammatory cytokine with multiple biological effects and is a
      potent inhibitor of gastric acid secretion, and IL-1RN has been shown to be
      associated with enhanced IL-1beta production in vitro. Recently, it was reported
      that the pro-inflammatory genotypes, IL-1B -31 C/+ and IL-1RN *2/*2, were
      associated with an increased risk of gastric cancer in a Caucasian population. We
      tested the association between the polymorphisms and 190 gastric cancer, 117
      duodenal ulcer, and 172 healthy subjects as controls in the Korean population.
      The allele frequency of IL-1B -31 C was more prevalent in Korean (51%) than in
      Caucasian (30%), while the frequency of IL-1RN *2 allele was less in Korean (6%)
      than in Caucasian (27%). Using the IL-1B TT genotype as a reference group, the CC
      genotype was not associated with an increased risk of gastric cancer or duodenal
      ulcer in the Korean population (odds ratios (OR)=0.90, 95% confidence interval
      (CI)=0.50-1.64; OR=0.72, 95% CI=0.36-1.46, respectively). Similarly, IL-1RN*2 was
      not a risk genotype for either gastric cancer or duodenal ulcer. No association
      was recognized on the haplotype analysis of the two genes, either. Our results
      did not support the previous report that IL-1B -31 C/IL-1RN*2 polymorphisms were
      associated with an increased risk of gastric cancer. The lack of association with
      duodenal ulcer also suggested that the polymorphisms were not directly related to
      the acid-secreting capability.

PMID- 12788305
TI  - Modulation of immune response in Plasmodium falciparum malaria: role of IL-12, IL
      18 and TGF-beta.
AB  - The interaction between pro- and anti-inflammatory cytokines such as interleukin
      12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta)
      plays an important role in malaria pathogenesis and outcome, modulating the
      immunoresponse in Plasmodium falciparum malaria. In our previous studies, we
      analyzed the plasmatic levels of IL-12, IL-18 and TGF-beta in 105 African
      children with different degrees of malaria and we correlated the production of
      these cytokines with the severity of the disease. The aim of the present study
      was to analyze with a mathematical model, taking into account all the
      relationships between these cytokines and the parameter variations involved in
      malaria pathogenesis that influence the results of each type of treatment or
      therapeutic protocol on patients at different stages of the disease. A
      mathematical correlation was demonstrated between the levels of pro-inflammatory
      and anti-inflammatory cytokines, and from this it was possible to build curves of
      reference in which each patient was positioned based on IL-12 level. Our data,
      obtained in patients with mild and severe diseases, demonstrate that the levels
      of IL-12 represent a reliable parameter to predict the progression of the
      disease, which may be complemented or modulated by administration of IL-18 and
      TGF-beta. Our findings provide future implications for an immune therapy against
      the P. falciparum malaria infection, especially in the early phase of the disease
      showing that a more aggressive outcome may be due to the lack of a balanced
      immune response.

PMID- 12788306
TI  - Macrophage migration inhibitory factor and development of type-1 diabetes in non
      obese diabetic mice.
AB  - AIMS/HYPOTHESIS: T-cell activation by specific antigen has been found to increase
      macrophage migration inhibitory factor (MIF) expression, indicating its role as
      an important feature of T-cell activation in vitro and in vivo. To date, the
      potential role of MIF in the development of autoimmune-mediated diabetes mellitus
      has not been studied. METHODS: MIF-mRNA expression in splenic lymphocytes of
      spontaneously diabetic non-obese diabetic (NOD) mice (n=6), cyclophosphamide
      treated NOD mice (n=6), 14-day-old non-diabetic NOD mice (n=7) and C57/Bl6
      control mice (n=6) was monitored using an internally standardised competitive
      reverse transcription-polymerase chain reaction, and the MIF-protein levels were
      determined using Western blot analysis. In addition, the impact of
      intraperitoneally administered recombinant MIF-protein treatment on diabetes
      incidence in NOD mice was evaluated. RESULTS: MIF-mRNA expression was markedly
      increased in splenic lymphocytes of spontaneously diabetic NOD mice as well as in
      8-week-old NOD mice treated with cyclophosphamide compared with 2-week-old non
      diabetic NOD and healthy C57BL/6 control mice. Western blot analyses showed
      decreased lymphocytic MIF-protein content in diabetic as well as in
      cyclophosphamide-treated animals compared with 2-week-old non-diabetic NOD and
      healthy C57BL/6 mice, probably as a consequence of increased protein secretion.
      Furthermore, treatment of NOD mice with recombinant MIF-protein at 25 microg
      twice a week, from age 6 to 11 weeks, led to an increased diabetes incidence
      (86%; n=7) compared with untreated control groups (55%; n=20) at week 34.
      CONCLUSIONS/INTERPRETATION: In this study, we report for the first time that MIF
      mRNA expression in splenic lymphocytes is up-regulated during development of cell
      mediated diabetes in non-NOD mice. The data of our preliminary study suggest a
      possible role of MIF in autoimmune-inflammatory events, such as type-1 diabetes
      and also that anti-MIF therapeutic strategy might serve to attenuate autoimmune
      processes.

PMID- 12788307
TI  - Prolactin enhances production of interferon-gamma, interleukin-12, and
      interleukin-10, but not of tumor necrosis factor-alpha, in a stimulus-specific
      manner.
AB  - Prolactin, an anterior pituitary hormone, has been shown to have a role in
      immunomodulation. Some reports have shown the importance of prolactin in
      activating lymphocytes and macrophages, while in hyperprolactinemia patients,
      prolactin was found to decrease lymphocyte activation and natural killer
      function. In the present work, at physiological (15ng/ml) and stress-induced
      levels (30ng/ml) of prolactin, interferon-gamma (IFN-gamma) and interleukin (IL)
      12 p70 levels, but not of IL-10 and tumor necrosis factor-alpha (TNF-alpha),
      increased significantly (p<0.05-0.006) in phytohemeagglutinin
      (PHA)+lipopolysaccharide (LPS)-stimulated whole blood. However, no such effect
      was observed at high concentrations of prolactin (100-300ng/ml). In addition,
      15ng/ml of prolactin reversed hydrocortisone suppressive effect on IFN-gamma, IL
      12 p70, and IL-10 production in PHA+LPS-stimulated whole blood. On the other
      hand, in LPS-stimulated whole blood, prolactin enhanced significantly (p=0.027)
      the production levels of IL-10, but not of IFN-gamma, IL-12 p70, and TNF-alpha,
      in non-concentration-dependent manner. These results suggest that prolactin
      modulates cytokine response during antigenic response, and this modulation is
      stimulus specific.

PMID- 12788308
TI  - Cytokine response to endotoxin in individuals heterozygous for the Delta32
      mutation of chemokine receptor CCR5.
AB  - Studies of mice with a targeted disruption of the CCR5 gene suggest that the CC
      chemokine receptor 5 (CCR5) is a determinant of the cytokine response to
      endotoxin. In humans, a naturally occurring mutation of the CCR5 gene is a 32
      basepair (bp) deletion which precludes the translation of the gene into a
      functional transmembrane protein. To evaluate the cytokine phenotype of
      heterozygosity for the 32 deletion, we studied the endotoxin-stimulated release
      of tumor necrosis factor-alpha, Interleukin (IL)-6, IL-8, IL-10, and IL-12 in
      whole blood ex-vivo of healthy volunteers and patients undergoing elective
      cardiac bypass surgery. This operation represents a major surgical trauma
      associated with ischemia-reperfusion-injury and triggers a profound inflammatory
      response. In these patients, cytokine plasma concentrations were measured during
      and after cardiac surgery. No difference was found between the frequencies of the
      observed and expected CCR5 genotypes in the groups of individuals studied.
      Furthermore, no significant difference in ex-vivo or peri- and postoperative
      cytokine plasma concentrations was detected between CCR5 wild-type homozygotes
      and individuals carrying one defective CCR5 allele. Our results indicate that
      heterozygosity for the 32bp deletion of CCR5 is not associated with an altered
      cytokine response to endotoxin or to a major surgical trauma when compared with
      individuals homozygous for the wild-type allele.

PMID- 12788310
TI  - Urinary tract stones--Part I: role of radiological imaging in diagnosis and
      treatment planning.
AB  - The modern management of urolithiasis requires a multi-disciplinary approach.
      Imaging plays a central role in both diagnosis and planning therapy of renal and
      ureteric calculi. This article reviews the current status of diagnosis and
      management of stone disease, and the contribution of radiological imaging in
      accurately triaging a given case to the most appropriate therapy.

PMID- 12788309
TI  - Modulation of pro- and anti-inflammatory cytokine production in very preterm
      infants.
AB  - BACKGROUND: In premature infants, outcome of infection-associated complications
      is heterogeneous despite advances in antibiotic treatment and diagnosis.
      Information on the immune response in preterm infants is limited. Immune
      modulatory strategies require detailed analysis of mediators and their kinetics.
      OBJECTIVE: To determine the kinetics of IL-1beta, TNFalpha, IL-6, IL-8, IL-10,
      gammaINF and G-CSF in preterm and term infants in an ex vivo cord blood culture
      (CBC) endotoxin model. DESIGN AND METHODS: Cord blood of 25 infants was obtained
      immediately after birth from the fetal side of the placenta and incubated in
      culture medium (RPMI 1640) in the presence or absence of 500 pg/ml
      lipopolysaccharide (LPS) for 48h. TNFalpha, IL-1beta, IL-6 and IL-8 were measured
      by sequential immunometric assay (IMMULITE, DPC Biermann, Germany); IL-10
      (Milenia Biotec, Bad Nauheim, Germany), gammaINF (Diaclone, Besancon, France) and
      G-CSF (R & D Systems, Wiesbaden, Germany) were determined by ELISA in
      supernatants at 0, 4, 8, 12, 24 and 48h. Infants were stratified into three
      gestational age groups (< or =32 weeks, 33-36 weeks, > or =37 weeks). Variations
      between the groups were first analyzed for significance by Kruskal-Wallis test
      and pairs were compared by Mann-Whitney-U test. Effects of gestational age,
      leucocyte count, hematocrit and frequency of antenatal steroid exposure were
      tested by linear regression analysis. To correct a possible impact of variable,
      WBC count, cytokine levels were adjusted according to individual leucocyte
      numbers. RESULTS: LPS-stimulated maximum levels of IL-6, IL-1beta,TNFalpha and G
      CSF in CBC were significantly lower in very preterm infants compared to more
      advanced gestational age groups. After adjusting the cytokine levels for 10(5)
      leucocytes, a significant effect of gestational age on IL-6 and G-CSF production
      (p<0.05) was detected. A non-significant trend towards reduced cytokine levels
      was observed following multiple antenatal steroid exposures. IL-10:TNFalpha ratio
      increased in very preterm neonates when compared with the advanced gestational
      age, although the increase was not significant. CONCLUSIONS: Pro-inflammatory
      cytokine activity in CBC correlates with gestational age, whereas IL-10 does not.
      Although ex vivo synthesis of IL-1beta, TNFalpha, IL-6, G-CSF in CBC depends in
      part on leucocyte numbers, IL-6 and G-CSF synthesis appeared to be related to
      immaturity. Non-significant effects of multiple antenatal steroid exposure and
      increased IL-10:TNFalpha ratio in preterm neonates, observed in a small sample
      size, warrant further investigation.

PMID- 12788311
TI  - Urinary tract stones--Part II: current status of treatment.
AB  - The majority of renal and ureteric stones are now managed by minimally invasive
      techniques, for example nephrostomy, ureteral stents, extracorporeal shockwave
      lithotripsy or percutaneous nephrolithotomy. A multi-disciplinary approach is
      necessary, and this review examines the status of modern stone therapy and the
      contribution of the radiology department.

PMID- 12788312
TI  - The role of MRI in the diagnosis of MS.
AB  - Magnetic resonance imaging (MRI) is the most widely used imaging technique in the
      investigation of multiple sclerosis (MS). Although MS remains a clinical
      diagnosis, MRI has become an invaluable tool in understanding and monitoring the
      disease, and is commonly used to confirm the clinical diagnosis. Various imaging
      techniques can be used but T2-weighted brain imaging remains the standard tool.
      The officially endorsed imaging criteria for MS places greater emphasis on the
      spatial and temporal distribution of lesions than on their individual appearance.
      This review focuses on the more typical findings in MS, and considers the current
      role of MRI in the diagnosis.

PMID- 12788313
TI  - Ultrasonography of intra-abdominal cystic lesions in the newborn.
AB  - Intra-abdominal cystic lesions are increasingly recognized in the newborn because
      of the advent of routine antenatal ultrasonography. As these lesions are often
      asymptomatic or non-specific in clinical presentation in the newborn, imaging by
      ultrasonography has an important role in diagnosis. We present a pictorial review
      of the commonly encountered intra-abdominal cystic lesions in the newborn, with
      emphasis on ultrasonographic features that can aid differentiation between the
      various lesions.

PMID- 12788314
TI  - Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing
      white matter tract invasion?
AB  - AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can
      demonstrate abnormalities distal to hyperintensities on T2-weighted images, and
      possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients
      with histologically confirmed supratentorial tumours, both gliomas (high and low
      grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences.
      Regions of interest (ROI) were drawn within the tumour, in white matter at
      various distances from the tumour and in areas of abnormality on DTI that
      appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a
      measure of white matter organization, was calculated for these ROI. RESULTS: The
      abnormality on DTI was larger than that seen on T2-weighted images in 10/13
      patients (77%) with high-grade gliomas. New abnormalities were seen in the
      contralateral white matter in 4/13 (30%) of these cases. In these high-grade
      tumours the RAI in areas of white matter disruption with normal appearance on T2
      weighted images was reduced (0.19+/-0.04). Even excluding patients with previous
      radiotherapy this difference remains significant. In all non high-grade tumours
      (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to
      the abnormalities shown on T2-weighted imaging and RAI measurements were not
      reduced (0.3+/-0.04). CONCLUSIONS: Subtle white matter disruption can be
      identified using DTI in patients with high-grade gliomas. Such disruption is not
      identified in association with metastases or low-grade gliomas despite these
      tumours producing significant mass effect and oedema. We suggest the changes in
      DTI may be due to tumour infiltration and that the DTI may provide a useful
      method of detecting occult white matter invasion by gliomas.

PMID- 12788315
TI  - Comparison of high-resolution contrast-enhanced 3D MRA with digital subtraction
      angiography in the evaluation of hepatic arterial anatomy.
AB  - AIM: To evaluate the validity of high-resolution contrast-enhanced three
      dimensional magnetic resonance angiography (MRA) in defining hepatic arterial
      anatomy and to compare this with digital subtraction angiography (DSA). MATERIALS
      AND METHODS: MRA and DSA were performed in 30 patients. MRA was performed with
      breath-hold, gadolinium-enhanced, three-dimensional, fast low-angle shot sequence
      with a 512 pixel matrix. MRA was compared with DSA in terms of image quality and
      depiction of hepatic arterial anatomy. The agreement in image quality between MRA
      and DSA was determined with the kappa statistic. RESULTS: With respect to image
      quality, there was excellent or good correlation between MRA and DSA for the
      common hepatic artery (kappa=0.85), proper hepatic artery (kappa=0.72),
      gastroduodenal artery (kappa=0.70), left hepatic artery (kappa=0.49), left
      gastric artery (kappa=0.50), splenic artery (kappa=0.84), and superior mesenteric
      artery (kappa=0.88). Poor correlation was found for the right hepatic artery
      (kappa=0.18) and right gastric artery (kappa=0.38). With regard to hepatic
      arterial anatomy, MRA correlated correctly with DSA in 28 of the 29 cases, i.e.
      97% of patients. CONCLUSION: MRA is a useful technique for the evaluation of the
      hepatic artery, and for the vast majority of patients, MRA can replace intra
      arterial DSA.

PMID- 12788316
TI  - Radiological patterns in HIV-associated pulmonary tuberculosis: comparison
      between HAART-treated and non-HAART-treated patients.
AB  - AIM: To evaluate whether highly active antiretroviral therapy (HAART) modifies
      radiographic appearances of pulmonary tuberculosis (TB), in terms of patterns and
      their relative frequencies, among patients with human immunodeficiency virus
      (HIV) infection. MATERIALS AND METHODS: Chest radiographs were obtained in 209
      HIV-infected patients with culture confirmed pulmonary TB. Computed tomography
      (CT) images were also reviewed for 42 patients whose chest radiographs were
      normal or showed questionable abnormalities. Imaging was evaluated for the
      presence and distribution of consolidation, cavitation, interstitial changes,
      pleural disease, adenopathy, and were classified as a primary or post-primary
      pattern. RESULTS: A post-primary pattern was more frequent after 1996 when HAART
      came into clinical use. Forty-four percent (77/176) of patients not on HAART had
      a post-primary pattern in comparison with 82% (27/33) of patients receiving HAART
      (p<0.001). A primary pattern was significantly more frequent (p<0.001), in
      patients with more severe immunosuppression (CD4 lymphocyte less than 200/mm(3)).
      CONCLUSION: HIV patients receiving HAART with pulmonary TB, had a post-primary
      pattern more frequently than those not receiving this treatment. This observation
      is consistent with the partial restoration of cell-mediated immunity that can be
      induced by HAART.

PMID- 12788317
TI  - Can the NHS Breast Screening Programme afford not to double read screening
      mammograms?
AB  - AIM: Rapid expansion of the National Health Service (UK) Breast Screening
      Programme (NHSBSP) to routinely invite women aged 50-70 years will result in many
      new readers undertaking screen reading. A timely method for assessing performance
      and preferably one that facilitates a steep learning curve will be required.
      MATERIALS AND METHODS: This unit screens a population of 88000 women aged 50-64
      years and double reads >90% films. A record is kept of proven screen-detected
      cancers not recalled for assessment by either the first or second reader but
      correctly recalled following third-reader arbitration. Individual readers'
      workload and recall rates are obtained by running an annual co-writer report. The
      results of this 7 year prospective audit are presented. RESULTS: In total 177167
      women were screened between 1/4/95 and 31/3/02 resulting in the detection of 1072
      cancers. Eighty-seven cancers (8.1%) were detected after arbitration. Individual
      readers recall to assessment rates and percentage of cases incorrectly returned
      to routine recall varied. Prompt feedback of missed/misinterpreted cases allowed
      both experienced and inexperienced readers to modify their recall thresholds for
      particular mammographic abnormalities. CONCLUSION: It is recommended this audit
      method is adopted by all units in the NHSBSP and that the Advisory Committee for
      Breast Cancer Screening review the policy of single versus double reading.

PMID- 12788318
TI  - Chest radiograph interpretation by medical students.
AB  - AIM: To assess the ability of final year medical students to interpret
      conventional chest radiographs. MATERIALS AND METHODS: Ten conventional chest
      radiographs were selected from a teaching hospital radiology department library
      that were good radiological examples of common conditions. All were conditions
      that a medical student should be expected to recognize by the end of their
      training. One normal radiograph was included. The radiographs were shown to 52
      final year medical students who were asked to describe their findings. RESULTS:
      The median score achieved was 12.5 out of 20 (range 6-18). There was no
      difference between the median scores of male and female students (12.5 and 12.3,
      respectively, p=0.82) but male students were more likely to be certain of their
      answers than female students (median certainty scores 23.0 and 14.0,
      respectively). The overall degree of certainty was low. On no radiograph were
      more than 25% of students definite about their answer. Students had received
      little formal radiology teaching (2-42 h, median 21) and few expressed an
      interest in radiology as a career. Only two (3.8%) students thought they were
      good at interpreting chest radiographs, 17 (32.7%) thought they were bad or
      awful. CONCLUSION: Medical students reaching the end of their training do not
      perform well at interpreting simple chest radiographs. They lack confidence and
      have received little formal radiological tuition. Perhaps as a result, few are
      interested in radiology as a career, which is a matter for concern in view of the
      current shortage of radiologists in the UK.

PMID- 12788319
TI  - Jumpers and fallers: a comparison of the distribution of skeletal injury.
AB  - AIM: The aim of this study was to compare the distribution of injuries between
      patients who have fallen and those who have jumped from a height, and to relate
      the mechanism of injury to the fractures sustained. MATERIALS AND METHODS: Three
      hundred and ninety-nine patients, admitted via Helicopter Emergency Medical
      Service (HEMS), classified as either having fallen or jumped from a height were
      included in the study. The radiographs from the primary survey, together with
      radiographs of specific injury sites were analysed. The distribution of injury
      was compared in the two groups. RESULTS: Of the 399 patients, 342 were fallers
      and 57 were jumpers. Jumpers had a higher Injury Severity Score (ISS), death rate
      and number of fractures per person. Jumpers sustained more rib fractures
      (particularly on the right), pelvic and lower limb fractures but fewer skull
      fractures. CONCLUSION: Jumpers tend to sustain different injuries to fallers. It
      is proposed that jumpers have a tendency to land feet-first and then try to break
      their falls on their dominant side, sustaining more right-sided rib fractures in
      the process. The patterns of injury that have emerged from this study have
      important implications for evaluating skeletal injuries in those who jump or fall
      from a height.

PMID- 12788320
TI  - Transvenous liver biopsy via the femoral vein.
AB  - AIM: To study the safety, effectiveness and diagnostic value of transvenous
      forceps biopsy of the liver in 54 patients with coagulopathy, gross ascites or
      morbid obesity and suspected liver disease in whom percutaneous liver biopsy was
      contraindicated. MATERIAL AND METHODS: Forceps biopsy of the liver via the
      femoral vein was attempted in 54 adult patients with advanced liver disease of
      unknown aetiology who had coagulation disorders (41 cases), gross ascites (11
      cases) or morbid obesity (two cases). In each patient two to six biopsies
      (average four) were taken using a radial jaw forceps inserted via the right or
      left femoral vein. RESULTS: The procedure was successful in 53 cases. Hepatic
      vein catheterization failed in one patient. Adequate liver tissue for diagnosis
      was obtained in 84% of cases. One patient developed delayed haemorrhage at 12 h
      from a capsular leak that was undetected during the biopsy procedure. This
      patient required blood transfusions and laparotomy to control bleeding. There
      were no deaths in the 53 patients studied. Transient minor chest and shoulder
      pain was encountered during sheath insertion into a hepatic vein in 23 patients.
      Three patients developed a femoral vein haematoma, which resolved with
      conservative treatment. CONCLUSION: Transvenous liver biopsy via the femoral vein
      is another safe, effective, simple alternative technique of biopsy when the
      percutaneous route is contraindicated.

PMID- 12788321
TI  - An unusual case of unilateral periureteral retroperitoneal fibrosis.

PMID- 12788322
TI  - Does testicular microlithiasis matter?

PMID- 12788323
TI  - Does testicular microlithiasis matter?

PMID- 12788325
TI  - Radiological findings in severe acute respiratory syndrome.

PMID- 12788326
TI  - Out of hours percutaneous nephrostomy.

PMID- 12788327
TI  - False-negative results in percutaneous adrenal biopsies in oncology patients.

PMID- 12788328
TI  - Can radiographers read screening mammograms?

PMID- 12788332
TI  - Alcohol and withdrawal: from animal research to clinical issues.
AB  - The withdrawal syndrome in alcohol-dependent patients appears to be a major
      stressful event whose intensity increases with repetition of detoxifications
      according to a kindling process. Disturbances in the balance between excitatory
      and inhibitory neural processes are reflected in a perturbed physical state while
      disturbances in the balance between positive and negative reinforcements are
      reflected in a perturbed mood state. Our purpose is to link the different
      behavioral outcomes occurring during withdrawal with specific biological brain
      mechanisms from the animal to the human being. Better understanding of the
      various biological mechanisms underlying withdrawal from alcohol will be the key
      to design and to apply appropriate pharmaceutical management, together with
      appropriate therapy aimed at inducing protracted abstinence.

PMID- 12788333
TI  - The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine
      (MDMA).
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is a relatively novel drug of abuse and
      as such little is currently known of its behavioural pharmacology. This review
      aims to examine whether MDMA represents a novel class of abused drug. MDMA is
      known as a selective serotonergic neurotoxin in a variety of animal species but
      acutely it is a potent releaser and/or reuptake inhibitor of presynaptic
      serotonin, dopamine, noradrenaline, and acetylcholine. Interaction of these
      effects contributes to its behavioural pharmacology, in particular its effects on
      body temperature. Drug discrimination studies indicate that MDMA and related
      drugs produce unique interoceptive effects which have led to their classification
      as entactogens. This is supported by results from other behavioural paradigms
      although there is evidence for dose dependency of MDMA-specific effects. MDMA
      also produces conditioned place preference but is not a potent reinforcer in self
      administration studies. These unique behavioural effects probably underlie its
      current popularity. MDMA is found in the street drug ecstasy but it may not be
      appropriate to equate the two as other drugs are routinely found in ecstasy
      tablets

PMID- 12788334
TI  - Memory retrieval in the day-old chick: a psychobiological approach.
AB  - This review integrates a series of studies conducted examining memory retrieval
      processes in the day-old chick. On the basis of these studies it is proposed that
      two processes are activated following retrieval of a memory. The first is an
      immediate memory recall or retrieval mechanism responsible for the chick's
      ability to remember the information and respond appropriately to the stimulus.
      The second process is activated following the completion of the first immediate
      retrieval phase. Further, it is proposed that the function of this secondary
      phase may be to allow for the modification of a memory undergoing storage
      processes. It is proposed that the processes of memory formation and memory
      retrieval are parallel at a cellular level, but at the functional level of
      information transfer they are interdependent.

PMID- 12788335
TI  - Glucocorticoid regulation of diverse cognitive functions in normal and
      pathological emotional states.
AB  - The glucocorticoid hormone cortisol is essential for many forms of regulatory
      physiology and for cognitive appraisal. Cortisol, while associated with fear and
      stress response, is also the hormone of energy metabolism and it coordinates
      behavioral adaptation to the environmental and internal conditions through the
      regulation of many neurotransmitters and neural circuits. Cortisol has diverse
      effects on many neuropeptide and neurotransmitter systems thus affecting
      functional brain systems. As a result, cortisol affects numerous cognitive
      domains including attention, perception, memory, and emotional processing. When
      certain pathological emotional states are present, cortisol may have a role in
      differential activation of brain regions, particularly suppression of hippocampal
      activation, enhancement of amygdala activity, and dendritic reshaping in these
      regions as well as in the ventral prefrontal cortex. The coordinated actions of
      glucocorticoid regulation on various brain systems such as those implicated in
      emotional processing can lead to perceptual and cognitive adaptations and
      distortions of events that may be relevant for understanding mood disorders.

PMID- 12788336
TI  - Fear and power-dominance motivation: proposed contributions of peptide hormones
      present in cerebrospinal fluid and plasma.
AB  - We propose that fear and power-dominance drive motivation are generated by the
      presence of elevated plasma and cerebrospinal fluid (CSF) levels of certain
      peptide hormones. For the fear drive, the controlling hormone is corticotropin
      releasing factor, and we argue that elevated CSF and plasma levels of this
      peptide which occur as a result of fear-evoking and other stressful experiences
      in the recent past are detected and transduced into neuronal activities by
      neurons in the vicinity of the third ventricle, primarily in the periventricular
      and arcuate hypothalamic nuclei. For the power-dominance drive, we propose that
      the primary signal is the CSF concentration of vasopressin, which is detected in
      two circumventricular organs, the subfornical organ and organum vasculosum of the
      lamina terminalis. We suggest that the peptide-generated signals detected in
      periventricular structures are transmitted to four areas in which neuronal
      activities represent fear and power-dominance: one in the medial hypothalamus,
      one in the dorsolateral quadrant of the periaqueductal gray matter, a third in
      the midline thalamic nuclei, and the fourth within medial prefrontal cortex. The
      probable purpose of this system is to maintain a state of fear or anger and
      consequent vigilant or aggressive behavior after the initial fear- or anger
      inducing stimulus is no longer perceptible. We further propose that all the
      motivational drives, including thirst, hunger and sexual desire are generated in
      part by non-steroidal hormonal signals, and that the unstimulated motivational
      status of an individual is determined by the relative CSF and plasma levels of
      several peptide hormones.

PMID- 12788337
TI  - Schizophrenia: from phenomenology to neurobiology.
AB  - Schizophrenia is a common and debilitating illness, characterized by chronic
      psychotic symptoms and psychosocial impairment that exact considerable human and
      economic costs. The literature in electronic databases as well as citations and
      major articles are reviewed with respect to the phenomenology, pathology,
      treatment, genetics and neurobiology of schizophrenia. Although studied
      extensively from a clinical, psychological, biological and genetic perspective,
      our expanding knowledge of schizophrenia provides only an incomplete
      understanding of this complex disorder. Recent advances in neuroscience have
      allowed the confirmation or refutation of earlier findings in schizophrenia, and
      permit useful comparisons between the different levels of organization from which
      the illness has been studied. Schizophrenia is defined as a clinical syndrome
      that may include a collection of diseases that share a common presentation.
      Genetic factors are the most important in the etiology of the disease, with
      unknown environmental factors potentially modulating the expression of symptoms.
      Schizophrenia is a complex genetic disorder in which many genes may be
      implicated, with the possibility of gene-gene interactions and a diversity of
      genetic causes in different families or populations. A neurodevelopmental rather
      than degenerative process has received more empirical support as a general
      explanation of the pathophysiology, although simple dichotomies are not
      particularly helpful in such a complicated disease. Structural brain changes are
      present in vivo and post-mortem, with both histopathological and imaging studies
      in overall agreement that the temporal and frontal lobes of the cerebral cortex
      are the most affected. Functional imaging, neuropsychological testing and
      clinical observation are also generally consistent in demonstrating deficits in
      cognitive ability that correlate with abnormalities in the areas of the brain
      with structural abnormalities. The dopamine and other neurotransmitter systems
      are certainly involved in the treatment or modulation of psychotic symptoms.
      These broad findings represent the distillation of a large body of disparate
      data, but firm and specific findings are sparse, and much about schizophrenia
      remains unknown.

PMID- 12788340
TI  - Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as
      HIV-1 inhibitors.
AB  - This review addresses key pharmacology and virology issues relevant in discovery
      and development of CCR5 antagonists as anti-HIV drugs, such as target validation,
      receptor internalization, allosterism, viral resistance and tropism. Recent
      progress in the discovery and development of CCR5 antagonists, SAR and clinical
      status are reviewed. Finally, modeling-based structure of CCR5 is discussed in
      the context of a small-molecule antagonism of the CCR5 receptor.

PMID- 12788341
TI  - Effect of O-glycosilation on the antioxidant activity and free radical reactions
      of a plant flavonoid, chrysoeriol.
AB  - Chrysoeriol and its glycoside (chrysoeriol-6-O-acetyl-4'-beta-D-glucoside) are
      two natural flavonoids extracted from the tropical plant Coronopus didymus. The
      aqueous solutions of both the flavonoids were tested for their ability to inhibit
      lipid peroxidation induced by gamma-radiation, Fe (III) and Fe (II). In all these
      assays chrysoeriol showed better protecting effect than the glycoside. The
      compounds were also found to inhibit enzymatically produced superoxide anion by
      xanthine/xanthine oxidase system; here the glycoside is more effective than the
      aglycone. The rate constants for the reaction of the compounds with superoxide
      anion determined by using stopped-flow spectrometer were found to be nearly same.
      Chrysoeriol glycoside reacts with DPPH radicals at millimolar concentration, but
      the aglycone showed no reaction. Using nanosecond pulse radiolysis technique,
      reactions of these compounds with hydroxyl, azide, haloperoxyl radicals and
      hydrated electron were studied. The bimolecular rate constants for these
      reactions and the transient spectra of the one-electron oxidized species
      indicated that the site of oxidation for the two compounds is different. Reaction
      of hydrated electron with the two compounds was carried out at pH 7, where
      similar reactivity was observed with both the compounds. Based on all these
      studies it is concluded that chrysoeriol exhibits potent antioxidant activity. O
      glycosylation of chrysoeriol decreases its ability to inhibit lipid peroxidation
      and reaction with peroxyl radicals. However the glycoside is a more efficient
      scavenger of DPPH radicals and a better inhibitor of xanthine/xanthine oxidase
      than the aglycone.

PMID- 12788342
TI  - Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB
      203207.
AB  - Twenty two analogues of SB-203207 have been prepared by total synthesis, and
      evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic
      core, removing either the terminal amino substituent or the sulfonyl group from
      the side chain, and altering either the carbon skeleton or stereochemistry of the
      isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA
      synthetase. Substituting the isoleucine residue with other amino acids produces
      inhibitors of the corresponding synthetases. In particular, a methionine
      derivative is 50-100 times more potent against methionyl tRNA synthetase than
      against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl
      synthetases.

PMID- 12788343
TI  - Superoxide dismutase mimetics. Part 2: synthesis and structure-activity
      relationship of glyoxylate- and glyoxamide-derived metalloporphyrins.
AB  - Novel glyoxylate- and glyoxamide-derived metalloporphyrins 26-58 were synthesized
      and evaluated as potential superoxide dismutase (SOD) mimetics. Relative to
      previously studied MnTBAP analogues, the glyoxylate-derived metalloporphyrins 32,
      39, and 54 and glyoxamide-derived metalloporphyrin 49, exhibited enhanced
      activity in the SOD assay and the majority of the analogues in the current series
      showed enhanced inhibition of lipid peroxidation and catalase activity.

PMID- 12788344
TI  - Synthesis and pharmacological characterization of a new benzoxazole derivative as
      a potent 5-HT3 receptor agonist.
AB  - N-(2-Benzoxazol-2-yl-ethyl)-guanidine hydrochloride (10) was synthesized and
      pharmacologically tested. This compound showed high affinity for the 5-HT(3)
      receptor (K(i)=0.77 nM) and potently triggered the von Bezold-Jarisch reflex
      (BJR) in rats with an ED(50)=0.52 microg/kg iv and intrinsic activity next to 1
      (i.a.=0.94). This stimulant effect was abolished by pretreatment with the 5-HT(3)
      receptor antagonist granisetron and was subject to a rapid and pronounced
      tachyphylaxis, due to desensitization of the peripheric cardiac 5-HT(3) receptor.
      Consequently, 10 acts as an in vivo 5-HT(3) antagonist inhibiting the BJR
      responses evoked by submaximal doses of 5-HT with an ID(50)=5.8 microg/kg iv.

PMID- 12788345
TI  - Synthesis and biological evaluation of 2,8-disubstituted 9-benzyladenines:
      discovery of 8-mercaptoadenines as potent interferon-inducers.
AB  - Recently, we have identified 9-benzyl-8-hydroxyadenines bearing an appropriate
      substituent (a butoxy, propylthio or butylamino group) at the 2-position as
      potent interferon (IFN)-inducers. Herein we report the design, synthesis, and IFN
      inducing activity of 8-substituted 9-benzyladenines possessing such an
      appropriate substituent at the 2-position. Introduction of the appropriate
      substituent into the 2-position of the adenine nucleus gave rise to expression of
      the activity even in 9-benzyladenines bearing no hydroxyl group at the 8
      position. An amino group at the 6-position and a hydroxyl or thiol group carrying
      an acidic proton at the 8-position are required to express excellent IFN-inducing
      activity. 9-Benzyl-2-butoxy-8-mercaptoadenine (9) indicated the most potent
      activity with MEC of 0.001 microM.

PMID- 12788346
TI  - Apoptotic activities of C2-ceramide and C2-dihydroceramide homologues against HL
      60 cells.
AB  - The apoptotic activities of non-natural ceramide homologues, C2-homo-ceramide, C2
      homo-dihydroceramide, C2-bishomo-ceramide and C2-bishomo-dihydroceramide, were
      examined using human leukemia HL-60 cells. The apoptotic activity was in order of
      C2-ceramide>C2-homo-ceramide approximately C2-bishomo-ceramide and the activities
      of the L-erythro- and D-erythro-ceramide homologues were similar. The
      morphological features of the cells, DNA fragmentations, proteolytic processing
      of pro-caspase-3 and the cleavage of PARP as the result of treatments with these
      homologues indicated that cell death was induced by apoptosis.

PMID- 12788347
TI  - Structure-activity relationships of antileishmanial and antimalarial chalcones.
AB  - A series of oxygenated chalcones which have been evaluated earlier for
      antimalarial activity (Plasmodium falciparum K1) were tested for antileishmanial
      activity against Leishmania donovani amastigotes. A comparison of structure
      activity relationships reveal that different physicochemical and structural
      requirements exist for these two activities. Antileishmanial activity is
      associated with less lipophilic chalcones, in particular those with 4'-hydroxyl
      substituted B rings and hetero/polyaromatic A rings. In contrast, chalcones with
      good antimalarial activity have alkoxylated B rings and electron-deficient A
      rings. Visualization of the steric and electrostatic fields generated from
      comparative molecular field analysis (CoMFA) indicate that the ring A of
      chalcones make a more significant contribution to antileishmanial activity while
      both rings A and B are important for antimalarial activity. Despite different
      requirements, two alkoxylated chalcones (8, 19) were identified which combined
      good antimalarial and antileishmanial activities.

PMID- 12788348
TI  - Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase:
      modifications of essential pyrrolidinone ring substituents.
AB  - We recently reported the first benzoic acid, 1-[4-carboxy-2-(3
      pentylamino)phenyl]-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent
      inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported
      potent neuraminidase inhibitors, does not contain a basic aliphatic amine or
      guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of
      influenza B neuraminidase. In the present study we further evaluated 8 as an
      inhibitor of human influenza A NA isolates, and it was effective against N2NA but
      found to be 160-fold less active against N1NA. We also synthesized analogues of 8
      involving moderate modifications of essential substituents on the pyrrolidinone
      ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11)
      analogues were prepared. Only the most conservative change (compound 9) resulted
      in continued effective inhibition of influenza A, in addition to a noteworthy
      increase in the activity of 9 for N1NA. The effectiveness of 9 against influenza
      B neuraminidase was furthermore improved 10-fold relative to 8, but this activity
      remained 50-fold poorer than for type A NA.

PMID- 12788349
TI  - Design of artificial nucleobases for the recognition of the AT inversion by
      triple-helix forming oligonucleotides: a structure-stability relationship study
      and neighbour bases effect.
AB  - We report herein on the synthesis, the incorporation into triplex forming
      oligonucleotides (TFO) and the recognition properties of a series of synthetic
      nucleosides designed for the specific recognition of an inverted A x T base pair
      in a pyrimidine triple helix motif. These analogues were designed on the basis of
      the results obtained with our previously reported compounds S and B(t), in order
      to define a structure-stability relationship. We report also on the chemical
      nature effect of the bases flanking S in the case of S-containing TFOs, in order
      to get further informations about the recognition process within the A x TxS
      triplet. This study establishes guidelines for the conception of more potent
      analogues for the recognition of both A x T and G x C inverted base pairs.

PMID- 12788350
TI  - Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes.
AB  - Several cis and trans bis-steroidal 1,2,4,5-tetraoxanes possessing amide terminus
      were synthesised and evaluated as antimalarials and antiproliferatives. The
      compounds exhibited submicromolar antimalarial activity against Plasmodium
      falciparum D6 and W2 strains. The existence of HN-C(O) moiety was found necessary
      for pronounced antimalarial and antiproliferative activity. In antiproliferative
      screen, the trans tetraoxane 6 was found to exhibit a pronounced cytotoxicity on
      14 cancer cell lines. In addition, tetraoxanes 11 and 12 exhibited significant
      cytotoxic activity too; microscopic examination of treated HeLa cells showed
      morphological appearance reminiscent for apoptosis (condensed and/or fragmented
      nuclei).

PMID- 12788351
TI  - Synthesis of a [6-pyridinyl-18F]-labelled fluoro derivative of WAY-100635 as a
      candidate radioligand for brain 5-HT1A receptor imaging with PET.
AB  - In recent years, considerable effort has been spent on the design, synthesis and
      pharmacological characterization of radiofluorinated derivatives of the 5-HT(1A)
      receptor antagonist, WAY-100635, for the in vivo study of these receptors in
      human brain with PET. (Pyridinyl-6)-fluoro- and (pyridinyl-5)-fluoro-analogues of
      WAY-100635 (6-fluoro and 5-fluoro-WAY-100635, 5a/6a) were synthesized as well as
      the corresponding chloro-, bromo- and nitro-derivatives as precursors for
      labelling (5b-d and 6b-d). Comparative radiolabelling of these precursors with
      fluorine-18 (positron-emitting isotope, 109.8 min half-life) clearly demonstrated
      that only ortho-fluorination in this pyridine series, and not meta-fluorination,
      is of interest for the preparation of a radioligand by nucleophilic
      heteroaromatic substitution. 6-[(18)F]Fluoro-WAY-100635 ([(18)F]5a) can be
      efficiently synthesized in one step, either from the corresponding 6-bromo
      precursor (using conventional heating at 145 degrees C for 10 min) or from the
      corresponding 6-nitro precursor (using microwave activation at 100 W for 1 min).
      Typically, 15-25 mCi (0.55-0.92 GBq) of 6-[(18)F]fluoro-WAY-100635 ([(18)F]5a, 1
      2 Ci/micromol or 37-72 GBq/micromol) were obtained in 50-70 min starting from a
      100 mCi (3.7 GBq) aliquot of a batch of cyclotron-produced [(18)F]fluoride. This
      (18)F-labelled radioligand is now being evaluated in PET studies.

PMID- 12788353
TI  - Association of chromatin with anticancer antibiotics, mithramycin and chromomycin
      A3.
AB  - Mithramycin and chromomycin A(3) are two anticancer antibiotics, which inhibit
      protein biosynthesis via transcription inhibition. They bind reversibly to DNA
      with (G.C) base specificity. At and above physiological pH in the absence of DNA,
      they form two types of complexes with Mg(2+), complex I (1:1 in terms of
      antibiotic: Mg(2+)) and complex II (2:1 in terms of antibiotic: Mg(2+)). These
      are the DNA binding ligands. In vivo, the antibiotics interact with chromatin, a
      protein-DNA complex. In order to understand the mode of action of these
      antibiotics at molecular level, we have carried out spectroscopic, gel
      electrophoretic and UV melting studies of complex I of these antibiotics with rat
      liver chromatin, nucleosome core particle and DNA stripped of all chromosomal
      proteins. Analysis of the results has led us to propose that the antibiotic:
      Mg(2+) complex binds to both nucleosomal and linker DNA in native chromatin.
      Histone proteins reduce the binding potential and accessibility of the complexes
      to the minor groove of (G.C) rich regions of chromosomal DNA. The antibiotic:
      Mg(2+) complex stabilizes DNA duplex and histone- DNA contacts in chromatin
      fiber. It also leads to the aggregation of chromatin fibers. From a comparison of
      the association of the antibiotic: Mg(2+) complexes with different levels of
      chromatin structure and their effects upon the structure, we suggest that the
      sugar moieties of the antibiotics play a role in the binding process.
      Significance of these results to understand the molecular basis of the
      transcription inhibition potential of the antibiotics in eukaryotes is discussed.

PMID- 12788352
TI  - Detection of acceptor sites for antisense oligonucleotides on native folded RNA
      by fluorescence spectroscopy.
AB  - Antisense strategy has high potential for curing diseases and studying gene
      functions by suppressing the translation step. For the strategy, it is essential
      to detect acceptor sites of antisense molecules on mRNA under physiological
      conditions. We propose a new analytical method for the detection of acceptor
      sites of antisense molecules with high sensitivity. 2'-O
      Methyloligoribonucleotide containing 2'-O-(1-pyrenylmethyl)uridine (OMUpy) was
      chosen as the fluorescence probe. The fluorescence intensity due to the pyrene in
      single-stranded OMUpy was scarcely observed. When OMUpy was hybridized with the
      complementary oligoRNA, the fluorescence intensity at 375 nm was remarkably
      increased. It was found that the increase was derived from the localization of
      the pyrene by the measurements of time-resolved fluorescence spectroscopy, CD and
      UV absorption spectra. These results suggest that the change of the fluorescence
      intensity of OMUpy can be a useful index to monitor hybridization. In this study,
      we chose Escherichia coli. 16S-rRNA as the model RNA and chose seven regions for
      probing by OMUpy based on the reported secondary structure of 16S-rRNA. The
      fluorescence intensity of an equimolar mixture of OMUpy with 16S-rRNA varied
      depending on the sequence. In particular, the increment in the system of OMUpy-8,
      which can hybridize with region 887-896 nt of 16S-rRNA, was most significant
      among the systems. These results indicated that the site targeted by OMUpy-8 was
      exposed to regulatory molecules, and suggest that the method presented here is
      useful to design antisense molecules.

PMID- 12788355
TI  - Synthesis and antimicrobial activity of tetrodecamycin partial structures.
AB  - An efficient synthetic approach to the core structure 5 of the novel polyketide
      antibiotic tetrodecamycin (1) was developed. This approach features the acid
      catalyzed cyclization of a tert-butyldimethylsilyl protected methyl alpha-(gamma
      hydroxyacyl) tetronate, leading to the novel tricyclic ring skeleton exhibited by
      5, and an efficient strategy for the parallel introduction of the cis-diol and
      exo-methylene function. In addition to 5, diastereomer 26, analogue 6 and several
      derivatives (16, 27-29) were prepared and evaluated for their antibacterial
      activities against Staphylococcus aureus (including MRSA) and Enterococcus
      faecalis and for their cytotoxic activities against human leukemia cell lines (HL
      60, Jurkat T-cells). While compound 5 did not inhibit the growth of the Gram
      positive pathogens (MICs >128 microg mL(-1)), analogue 6 and 2-naphthoyl
      derivative 27 showed promising antibacterial activities with MICs of 4-16 microg
      mL(-1). Remarkably, the antibacterial activity of these compounds was paralleled
      by cytotoxicity (IC(50) 10-23 microM). The reactive exo-methylene moiety was
      shown to be crucial, but not sufficient by its own, for both the antibacterial
      and the cytotoxic activities.

PMID- 12788354
TI  - 20-hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal
      vasoconstriction.
AB  - The effects of natural and synthetic eicosanoids on the diameter of rat
      interlobular arteries studied in vitro were compared to that of the potent,
      endogenous vasoconstrictor 20-HETE. Vasoconstrictor activity was optimum for
      chain lengths of 20-22 carbons with at least one olefin or epoxide between
      located between C(13)-C(15) and an oxygen substituent at C(20)-C(22). The
      presence of delta (Zou et al. Am. J. Physiol. 1996, 270, R228; Gebremedhin, D. et
      al. Am. J. Physiol. 1998, 507, 771)-, delta (Carroll et al. Am. J. Physiol. 1996,
      271, R863; Vazquez et al. Life Sci. 1995, 56, 1455)-, or delta (Imig et al.
      Hypertension 2000, 35, 307; Lopez et al. Amer. J. Physiol. 2001, 281, F420)
      olefins had no influence on the vasoconstrictor response whereas the introduction
      of a C(7)-thiomethylene enhanced potency. A sulfonamide or alcohol, but not a
      lactone, could replace the C(1)-carboxylate. These data were used to construct a
      putative binding domain map of the 20-HETE receptor consisting of: (i) a
      comparatively open, hydrophilic binding site accommodating the C(1)
      functionality; (ii) a hydrophobic trough spanning the olefins; (iii) a shallow
      pocket containing a critical pi-pi binding site in the vicinity of the pi (Ito et
      al. Am. J. Physiol. 1998, 274, F395; Quigley, R.; Baum, M.; Reddy, K. M.;
      Griener, J. C.; Falck, J. R. Am. J. Physiol. 2000, 278, F949)-olefin; and (iv) an
      oxyphilic binding site proximate to the omega-terminus.

PMID- 12788356
TI  - Synthesis and biological evaluation of novel turn-modified gramicidin S
      analogues.
AB  - The synthesis of novel gramicidin S analogues having additional functionalities
      in the turn region by employing a biomimetic approach is described. The
      preservation of beta-sheet character in all analogues was established by NMR and
      the biological activity was evaluated.

PMID- 12788357
TI  - Synthesis and structure-antifungal activity relationships of 3-aryl-5-alkyl-2,5
      dihydrofuran-2-ones and their carbanalogues: further refinement of tentative
      pharmacophore group.
AB  - Two series of 3-(substituted phenyl)-5-alkyl-2,5-dihydrofuran-2-ones related to a
      natural product, (-)incrustoporine, were synthesized and their in vitro
      antifungal activity evaluated. The compounds with halogen substituents on the
      phenyl ring exhibited selective antifungal activity against the filamentous
      strains of Absidia corymbifera and Aspergillus fumigatus. On the other hand, the
      influence of the length of the alkyl chain at C(5) was marginal. The antifungal
      effect of the most active compound against the above strains was higher than that
      of ketoconazole, and close to that of amphotericin B. In order to verify the
      hypothesis about a possible relationship between the Michael-accepting ability of
      the compounds and their antifungal activity, a series of simple carbanalogues, 2
      (substituted phenyl)cyclopent-2-enones, was prepared and subjected to antifungal
      activity assay as well.

PMID- 12788358
TI  - Structure-activity relationship study of taxoids for their ability to activate
      murine macrophages as well as inhibit the growth of macrophage-like cells.
AB  - A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions
      has been designed, synthesized and evaluated for their potency to induce NO and
      TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive
      C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for
      their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3.
      The SAR-study has shown that the nature of the substituents at these positions
      have critical effect on the induction of TNF and NO production by Mphi. Positions
      C-3' and C-10 are the most flexible and an intriguing effect of the length of the
      substituents at the C-10 position is observed for taxoids bearing a straight
      chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is
      required for the activity, while only hydroxyl or acetyl substituents seem to be
      tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine
      side chain of the taxoids is an absolute requirement for macrophage activation.
      It has also been clearly shown that there is no correlation between the ability
      of the taxoids to induce TNF/NO production in C3H/HeN Mphi and the cytotoxicity
      against Mphi-like cells.

PMID- 12788359
TI  - QSAR and 3D-QSAR of phenothiazine type multidrug resistance modulators in
      P388/ADR cells.
AB  - A series of 25 phenothiazines and structurally related compounds was investigated
      by QSAR (quantitative structure activity relationship) and 3D-QSAR methods with
      respect to their MDR (multidrug resistance) reversing activity in P388/ADR-
      murine leukemia cell line resistant to ADR (adriamycin). The objective was to
      outline structural properties important for the investigated activity. Different
      measures for MDR reversal were used and compared. Two 3D-QSAR approaches were
      applied-CoMFA (comparative molecular field analysis) and CoMSIA (comparative
      molecular similarity indices analysis). Both, neutral and protonated forms of the
      compounds were investigated. Molecular models with good predictive power were
      derived using a hydrophobic field alone and a combination of steric, hydrophobic,
      and hydrogen bond acceptor fields of the compounds. In the combined models
      highest contribution of the hydrogen bond acceptor field was noticed. Thus, the
      dominant role of the hydrophobic and hydrogen bond acceptor fields for MDR
      reversing activity of the investigated compounds was demonstrated. The structural
      regions responsible for the differences in anti-MDR activity were analyzed in
      respect to their hydrophobic, hydrogen bond acceptor and steric nature. The
      results may direct design of new phenothiazines and related compounds as MDR
      modulators.

PMID- 12788360
TI  - Toward protein-cleaving catalytic drugs: artificial protease selective for
      myoglobin.
AB  - A protein-cleaving catalyst highly selective for a disease-related protein can be
      used as a catalytic drug. As the first protein-cleaving catalyst selective for a
      protein substrate, a catalyst for myoglobin (Mb) was designed by attaching the
      Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinatorial
      method using peptide nucleic acid monomers as building units. Various linkers
      were inserted between the catalytic Co(III) center and the binding site of the Mb
      cleaving catalyst. Kinetic data revealed catalytic turnover of the Mb cleavage by
      the Cu(II) or Co(III) complex. MALDI-TOF MS revealed cleavage of the polypeptide
      backbone of Mb at selected positions. N-Terminal sequencing of the cleavage
      products identified the cleavage site and provided evidence for the hydrolytic
      nature of the Mb cleavage. Various chelating ligands were tested as the ligand
      for the Co(III) center of the Mb-cleaving catalyst. Among the nine chelating
      ligands examined, only cyclen and its triaza-monooxo analogue manifested
      catalytic activity.

PMID- 12788361
TI  - Synthesis and bioevaluation of glycosyl ureas as alpha-glucosidase inhibitors and
      their effect on mycobacterium.
AB  - Glycosyl amino esters (2-13) on reaction with different isocyanates resulted in
      quantitative conversion to glycosyl ureas (14--32). Few of the selected ureas (15
      20, 22-28, 30 and 32) on cyclative amidation with DBU/TBAB/4 A MS gave respective
      dihydropyrimidinones in fair to good yields (33-47). The compounds were screened
      for alpha-glucosidase inhibitory activity and two (19 and 23) of them showed
      strong inhibition against rat intestinal alpha-glucosidase. The compounds were
      also screened against Mycobacterium aurum, however, only one (19) of them
      exhibited marginal antitubercular activity.

PMID- 12788362
TI  - New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde
      thiosemicarbazones. synthesis, spectral studies and in vitro anti-amoebic
      activity.
AB  - Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type
      [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro
      thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via
      the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to
      the metal ion were confirmed by spectral data. These compounds were screened in
      vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal
      properties. Enhancement of antiamoebic activity resulted due to the introduction
      of palladium metal in the thiosemicarbazone moiety. The most promising of the
      group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)]
      comparable to that of metronidazole.

PMID- 12788363
TI  - Substituted hepta-1,6-dien-3-ones with green/fruity odours green/galbanum
      olfactophore model.
AB  - Following an analysis of available SAR data on green/galbanum-smelling molecules,
      a series of new 2-substituted hepta-1,6-dien-3-ones and their analogues were
      prepared and their olfactory properties evaluated. The study allowed to select
      efficient new odourants-potential substitutes for natural galbanum oil-and to
      generate an olfactophore model for the green/galbanum note.

PMID- 12788364
TI  - Effect of 3-5 monocyclizations of angiotensin II and 4-aminoPhe6-Ang II on AT2
      receptor affinity.
AB  - The endogenous angiotensin II (Ang II) and the synthetic AT(2) selective agonist
      4-aminoPhe(6)-Ang II respond very differently to identical cyclizations.
      Cyclizations of Ang II by thioacetalization, involving the 3 and 5 amino acid
      residue side chains, provided ligands with almost equipotent binding affinities
      to Ang II at the AT(2) receptor. In contrast, the same cyclization procedures
      applied on the AT(2) selective 4-aminoPhe(6)-Ang II delivered significantly less
      potent AT(2) receptor ligands, although the AT(2)/AT(1) selectivity was still
      very high. The fact that different structure-activity relationships are observed
      after imposing conformational restrictions on Ang II and 4-aminoPhe(6)-Ang II,
      respectively, suggests that the peptides, despite large similarities might adopt
      quite different backbone conformations when binding to the AT(2) receptor.

PMID- 12788365
TI  - Peptide-based inhibitors of hepatitis C virus full-length NS3 (protease
      helicase/NTPase): model compounds towards small molecule inhibitors.
AB  - From L-alpha-aminobutyric acid (Abu) a set of electrophilic and non-electrophilic
      replacements for the P1 cysteine of substrate and product inhibitors of hepatitis
      C virus full-length NS3 (protease-helicase/NTPase) serine protease have been
      synthesised and coupled to a model pentapeptide furnishing a set of hexapeptide
      inhibitors. Promising inhibitory activities with K(i) values of 0.18 microM (11b,
      P1 electrophilic alpha,beta-unsaturated ketone), 0.46 microM (12e, P1
      electrophilic alkyl ketone) and 0.98 microM (10e, P1 non-electrophilic alkenyl
      alcohol as diastereomeric mixture). The reference hexapeptide product inhibitor
      had a K(i) value of 1.54 microM (14, P1 Abu-OH). The electrophilic inhibitors
      exhibit increased potency as compared with the corresponding product inhibitor,
      and notably also the non-electrophilic P1 alkenyl alcohol 10e. This represents
      the first example of non-electrophilic inhibitors that are not P1 amides or
      product inhibitors.

PMID- 12788366
TI  - Studies on the interaction of the antibiotic moenomycin A with the enzyme
      penicillin-binding protein 1b.
AB  - The interaction of a moenomycin derivative with the enzyme penicillin binding
      protein 1b (PBP 1b) has been studied by means of STD NMR. The results obtained
      initiated the synthesis of a number of moenomycin derivatives modified in unit A
      including a moenomycin-ampicillin conjugate and determination of their antibiotic
      activities. A protocol is described that allows studying the interaction of
      moenomycin analogues with PBP 1b by fluorescence correlation spectroscopy.

PMID- 12788367
TI  - Aminothiazole derivatives with antidegenerative activity on cartilage.
AB  - A series of 2-dialkylamino-N-(4-substituted thiazolyl-2)acetamides and 3
      dialkylamino-N-(4-substituted thiazolyl-2)propionamides were synthesized and
      evaluated for their anti-inflammatory activity. Encouraging results led us to
      investigate the effect of these compounds on NO production and GAGs release.
      Their effects were evaluated in vitro on the metabolism of pig cartilage, treated
      with IL-1beta. The amount of glycosaminoglycans (GAGs) and the production of
      nitric oxide (NO) in the culture medium were determined. The results, obtained,
      showed that all compounds, in the presence of IL-1beta, blocked the cartilage
      breakdown, with different behavior. A quantitative structure-activity
      relationship (QSAR) study was performed.

PMID- 12788368
TI  - Structure-activity studies of a series of dipyrazolo[3,4-b:3',4'-d]pyridin-3-ones
      binding to the immune regulatory protein B7.1.
AB  - The interaction of co-stimulatory molecules on T cells with B7 molecules on
      antigen presenting cells plays an important role in the activation of naive T
      cells. Consequently, agents that disrupt these interactions should have
      applications in treatment of transplant rejection as well as autoimmune diseases.
      To this end, specific small molecule inhibitors of human B7.1 were identified and
      characterized. Herein, we report the identification of potent small molecule
      inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we
      identified several leads that prevented the interaction of B7.1 with CD28 with
      activities in the nanomolar to low micromolar range. One of these, the
      dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain
      of human B7.1 at equimolar stoichiometry. With this as a starting point, we
      report here the synthesis and initial in vitro structure-activity relationships
      of a series of these compounds.

PMID- 12788369
TI  - QSAR of apoptosis induction in various cancer cells.
AB  - In continuing our QSAR study of apoptosis, we consider in this report the action
      of phenolic compounds on Ramos cells (non-Hodgkins B-cell lymphoma): the effect
      of O-8-thapsigargin analogues on human prostate cancer cells, Tsu-Pr-1 and the
      induction of apoptosis of a complex set of congeners on human fibrosarcoma cells
      HT 1080. The human prostate cancer cells activity is very similar to that of the
      Ramos cells. While the QSAR for the fibrosarcoma cells resembles that of our
      earlier study with L1210 leukemia cells. The two different types of QSAR suggest
      at least two quite different types of receptors for the induction of apoptosis.

PMID- 12788370
TI  - A novel neoglycopeptide building block.
AB  - The synthesis of a neoglycopeptide building block is described. The key step is a
      cycloaddition where the chemistry is orthogonal to standard glycosyl transfer
      methodology. Also described is some exploratory chemistry of the building block.

PMID- 12788371
TI  - Modulation of the skeletal muscle Ca2+ release channel/ryanodine receptor by
      adenosine and its metabolites: a structure-activity approach.
AB  - Activation of ryanodine receptor (RyR) from skeletal muscle sarcoplasmic
      reticulum by adenosine and adenosine's metabolites was studied. The purines
      tested increased the [3H]-ryanodine binding as follows:
      xanthine>adenosine>adenine >inosine>/=uric acid>hypoxanthine. The enhanced [3H]
      ryanodine binding did not involve change in the RyR-Ca(2+) sensitivity and was
      due mainly to lower values in the affinity constant (K(d)) that corresponded with
      an increase in the association rate constant (K(+1)). [3H]-ryanodine maximum
      binding (B(max)) was much less affected. Adenosine and inosine effects were
      dependent on the presence beta-glycosidic bond within the ribose ring, since the
      combination of adenine or hypoxanthine with ribose was not able to emulate the
      nucleosides' original activation. Competition experiments with AMP-PCP, a non
      hydrolyzable analogue of ATP, evidenced a nucleotide's inhibitory influence on
      the adenosine and xanthine activation of the RyR. As a result of a Quantitative
      Structure-Activity Relationship (QSAR) study, we found a significant correlation
      between the modulation by adenosine and its metabolites on RyR activity and the
      components of their calculated dipole moment vector. Our results show that the
      ribose moiety and the dipole moment vector could be factors that make possible
      the modulation of the RyR activity by adenosine and its metabolites.

PMID- 12788372
TI  - Mitochondria-assisted cell suicide: a license to kill.
AB  - Although the mechanisms that underlie cardiac cell death remain cryptic, there is
      emerging evidence that mitochondria may play a pivotal role in this process. The
      mitochondrion initially deemed the "power house " is now considered to be a
      central integration site for biological signals that promote cell life or cell
      death. Since mitochondria contain the necessary apoptotic machinery to activate
      the cell-death pathway, it is now appreciated that mitochondria play a key
      decision-making role in whether a cell will live or die following a noxious
      signal-literally a "license to kill ". Permeability changes to the outer
      mitochondrial membrane, collapse of membrane potential, permeability pore complex
      assembly, release of cytotoxic proteins and caspase activation are associated
      with the mitochondrial-death pathway. Members of the Bcl-2 gene family can
      promote or suppress cell death by modulating mitochondrial function. Activation
      of the mitochondrial-death pathway has been reported in several cardiac
      pathologies and believed to account for the reported apoptosis observed in these
      disease entities. Given the meager and limited ability of cardiac muscle for
      repair or self-renewal after injury, the inordinate loss of cardiac cells is
      considered to be a key underlying factor in ventricular remodeling and decline in
      ventricular performance in patients with ischemic heart disease or post
      myocardial infarction. This review will provide mechanistic insight into the
      involvement and contribution of the mitochondrion as a regulator of cell death in
      health and disease with particular focus on the heart.

PMID- 12788373
TI  - Mitochondrial K(ATP) channels in preconditioning.

PMID- 12788374
TI  - Serum response factor: toggling between disparate programs of gene expression.
AB  - Serum response factor (SRF) is a widely expressed transcription factor involved
      in orchestrating disparate programs of gene expression linked to muscle
      differentiation and cellular growth. Vascular smooth muscle cell (SMC)
      differentiation, for example, is marked by the coordinate expression of several
      contractile and cytoskeletal genes regulated directly by SRF through one or more
      CArG-box elements in the immediate vicinity of transcription start sites. In
      vascular disease, this CArG-dependent program of SMC differentiation is
      compromised and numerous CArG-dependent early growth-response genes are
      activated. Thus, SRF must toggle between programs of SMC differentiation and
      growth depending on local environmental cues. Moreover, SRF must distinguish
      between a course of SMC differentiation and programs of cardiac and skeletal
      muscle differentiation. Several mechanisms exist to ensure context- and cell
      specific programs of SRF-dependent gene expression. These include regulated
      expression, DNA binding, and alternative splicing of SRF, flanking sequences
      adjacent to and chromatin remodeling of CArG boxes, RhoA-mediated alterations in
      the cytoskeleton, and association of SRF with a variety of cell-restricted
      cofactors including the recently discovered myocardin coactivator. Although many
      SMC-differentiation genes require critical evolutionarily conserved CArG boxes
      for SMC-restricted promoter activity in cultured cells and transgenic mice, the
      expression of a growing number of similarly restricted genes appears to be
      independent of SRF. Thus, parallel circuits of gene transcription have evolved
      for the appropriate expression of all genes that define mammalian SMC lineages.
      The purpose of this review is to summarize the history and progress made in SRF
      research with emphasis on the role this transcription factor plays in
      facilitating a program of SMC-restricted gene expression.

PMID- 12788375
TI  - Myocardial damage and repair.

PMID- 12788376
TI  - The radical balance between life and death.

PMID- 12788377
TI  - The matrix strikes back: evidence for autoregulatory mechanisms in
      metalloproteinase regulation.

PMID- 12788378
TI  - Transplantation of neonatal cardiomyocytes after permanent coronary artery
      occlusion increases regional blood flow of infarcted myocardium.
AB  - BACKGROUND: Cellular cardiomyoplasty is a promising approach for rebuilding scar
      tissue after acute myocardial infarction. However, the angiogenic potential of
      transplanted immature cardiomyocytes and their effect on regional myocardial
      blood flow (RMBF) after coronary artery occlusion remain to be evaluated. METHODS
      AND RESULTS: Intramyocardial injection of cultured neonatal cardiomyocytes (4 x
      10(6) cells/50-70 microliter) into the scar 1 week after permanent coronary
      occlusion in rats resulted in improved RMBF in the infarct 4 weeks after
      transplantation (radioactive microspheres, 0.97 +/- 0.18 ml/min/g) in comparison
      to medium-injected hearts (0.61 +/- 0.11 ml/min/g, P < 0.047). The macroscopic
      perfusion defect after in vivo staining with the blue dye 50% Uniperse blue was
      significantly smaller in the cell transplantation group (1.5 +/- 0.3% of the
      heart) compared to the medium group (3.0 +/- 0.6%, P < 0.017). Clusters of
      engrafted cells within the scar demonstrated a high capillary density (1217 +/-
      114 perfused (blue) capillaries/mm(2)); however, in the scar tissue itself
      capillary density in the cell group (156 +/- 62/mm(2)) did not significantly
      differ from the medium group (125 +/- 10/mm(2)), suggesting that neo-angiogenesis
      was confined to regions of successful engraftment (non-infarcted tissue: 1924 +/-
      114 perfused capillaries/mm(2)). The transplantation group was characterized by
      smaller diastolic and systolic left ventricular volumes, as assessed by
      intravenous ventriculography, along with thickened infarcts (0.93 +/- 0.07 vs.
      0.75 +/- 0.04 mm, P < 0.020) and lower infarct expansion indices (0.64 +/- 0.07
      vs. 0.83 +/- 0.06, P < 0.023), as determined by post-mortem morphometry of
      histologic slides. CONCLUSIONS: Transplantation of neonatal cardiomyocytes
      induced neo-angiogenesis in zones of successful cell engraftment within the scar,
      which effectively enhanced tissue perfusion.

PMID- 12788379
TI  - H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent
      activation of distinct kinase pathways.
AB  - Reactive oxygen species (ROS) can act as signaling molecules to stimulate either
      hypertrophy or apoptosis in cardiac myocytes. We tested the hypothesis that the
      phenotypic effects of ROS are due to differential, concentration-dependent
      activation of specific kinase signaling pathways. Adult rat ventricular myocytes
      were exposed to H(2)O(2) over a broad concentration range (10-1000 microM). Low
      concentrations of H(2)O(2) (10-30 microM) increased protein synthesis without
      affecting survival. Higher concentrations of H(2)O(2) (100-200 microM) increased
      apoptosis (assessed by TUNEL). Still higher concentrations of H(2)O(2) (300-1000
      microM) caused both apoptosis and necrosis. A hypertrophic concentration of
      H(2)O(2) (10 microM) increased the activity of ERK1/2, but not that of JNK, p38
      kinase or Akt. An apoptotic concentration of H(2)O(2) (100 microM) activated JNK,
      p38 kinase and Akt, and further activated ERK1/2. The MEK1/2 inhibitor U0126
      prevented the hypertrophic effect of 10 microM H(2)O(2). The apoptotic effect of
      100 microM H(2)O(2) was inhibited bya dominant-negative JNK adenovirus, and was
      potentiated by U0126 or an Akt inhibitor. Thus, the concentration-dependent
      effects of ROS on myocyte hypertrophy and growth are due, at least in part, to
      the differential activation of specific kinase signaling pathways that regulate
      hypertrophy and apoptosis.

PMID- 12788380
TI  - Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial
      hypertrophic cardiomyopathy.
AB  - Mutations causing familial hypertrophic cardiomyopathy (HCM) have been described
      in at least 11 genes encoding cardiac sarcomeric proteins. In this study, three
      previously unknown deletions have been identified in the human cardiac genes
      coding for beta-myosin heavy chain (MYH7 on chromosome 14) and myosin-binding
      protein-C (MYBPC3 on chromosome 11). In family MM, a 3-bp deletion in MYH7 was
      detected to be associated with loss of glutamic acid in position 927 (DeltaE927)
      of the myosin rod. In two other families (HH and NP, related by a common founder)
      a 2-bp loss in codon 453 (exon 16) of MYBPC3 was identified as the presumable
      cause of a translation reading frame shift. Taken together 15 living mutation
      carriers were investigated. Six deceased family members (with five cases of
      premature sudden cardiac death (SCD) in families MM and NP) were either obligate
      or suspected mutation carriers. In addition to these mutations a 25-bp deletion
      in intron 32 of MYBPC3 was identified in family MM (five carriers) and in a
      fourth family (MiR, one HCM patient, three deletion carriers). In agreement with
      the loss of the regular splicing branch point in the altered intron 32, a
      splicing deficiency was observed in an exon trapping experiment using MYBPC3 exon
      33 as a test substrate. Varying disease profiles assessed using standard
      clinical, ECG and echocardiographic procedures in conjunction with mutation
      analysis led to the following conclusions: (1) In family MM the DeltaE927
      deletion in MYH7 was assumed to be associated with complete penetrance. Two cases
      of reported SCD might have been related to this mutation. (2) The two families,
      HH and NP, distantly related by a common founder, and both suffering from a 2-bp
      deletion in exon 16 of MYBPC3 differed in their average phenotypes. In family NP,
      four cases of cardiac death were documented, whereas no cardiac-related death was
      reported from family HH. These results support the notion that mutations in HCM
      genes may directly determine disease penetrance and severity; however, a
      contribution of additional, unidentified factors (genes) to the HCM phenotype can
      at least in some cases-not be excluded. (3) The deletion in intron 32 of MYBPC3
      was seen in two families, but in both its relation to disease was not
      unequivocal. In addition, this deletion was observed in 16 of 229 unrelated
      healthy individuals of the population of the South Indian states of Kerala and
      Tamil Nadu. It was not seen in 270 Caucasians from Russia and western Europe.
      Hence, it is considered to represent a regional genetic polymorphism restricted
      to southern India. The association of the deletion with altered splicing in
      transfected cells suggests that this deletion may create a "modifying gene",
      which is per se not or only rarely causing HCM, but which may enhance the
      phenotype of a mutation responsible for disease.

PMID- 12788381
TI  - Combined loss of neuronal and endothelial nitric oxide synthase causes premature
      mortality and age-related hypertrophic cardiac remodeling in mice.
AB  - Deficiency of either neuronal nitric oxide synthase (NOS1) or endothelial nitric
      oxide synthase (NOS3) leads to cardiac hypertrophy in mice. Loss of both produces
      concentric left ventricular (LV) remodeling, in which increased wall thickness is
      accompanied by reduced cavity size. In humans, this phenotype develops in elderly
      hypertensive patients and independently predicts mortality. Accordingly, we
      tested the hypothesis that NOS1/3(-/-) mice have reduced longevity compared to
      either NOS1(-/-) or NOS3(-/-). Survival data on colonies of NOS1(-/-) (n = 295),
      NOS3(-/-) (n = 525), and NOS1/3(-/-) (n = 331) mice were collected for 2 years.
      NOS1(-/-) mice had increased mortality compared to NOS3(-/-) (relative risk, RR
      2.5, P < 0.001), whereas NOS1/3(-/-) fared significantly worse (RR 7.3, P < 0.001
      vs. NOS3(-/-)). Importantly, gender did not affect survival in NOS1(-/-) or NOS3(
      /-), but male NOS1/3(-/-) mice had 2-fold increased mortality compared to
      females. NOS1/3(-/-) mice developed progressive myocyte hypertrophy and
      interstitial fibrosis with age. NOS1/3(-/-) mice underwent in vivo hemodynamic
      analysis with a combined pressure-volume catheter to assess age-related
      cardiovascular changes. Compared with control, NOS1/3(-/-) demonstrated
      hypertension and hypercontractility at all ages, and developed passive diastolic
      dysfunction with increasing age. Thus, combined deficiency of NOS1 and NOS3
      causes increased mortality, myocyte hypertrophy, and an age-associated increase
      in ventricular stiffness. These findings suggest that cardiac NO signals may play
      an essential role in successful cardiac aging.

PMID- 12788382
TI  - Cardiac-specific overexpression of catalase rescues ventricular myocytes from
      ethanol-induced cardiac contractile defect.
AB  - Oxidative stress is intimately involved in alcoholic cardiomyopathy. Catalase is
      responsible for detoxification of hydrogen peroxide (H(2)O(2)) and may interfere
      with ethanol-induced cardiac toxicity. To test this hypothesis, a transgenic
      mouse line was produced to overexpress catalase (~50-fold) in the heart, ranging
      from sarcoplasm, the nucleus and peroxisomes within myocytes. Mechanical and
      intracellular Ca(2+) properties were evaluated in ventricular myocytes from
      catalase transgenic (CAT) and wild-type FVB mice. Protein abundance of sarco
      (endo) plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), Na(+)/Ca(2+)
      exchanger (NCX), dihydropyridine Ca(2+) receptor (DHPR), ryanodine receptor
      (RyR), Akt and phosphorylated Akt (pAkt) were measured by western blot. CAT
      itself did not alter body and organ weights, as well as myocyte contractile
      properties. Acute exposure of ethanol elicited a concentration-dependent
      depression in cell shortening and intracellular Ca(2+) in FVB mice with maximal
      inhibitions of 65.4% and 35.8%, respectively. The ethanol-induced cardiac
      depression was significantly attenuated in myocytes from CAT with maximal
      inhibitions of 42.4% and 27.3%. CAT also abrogated the ethanol-induced inhibition
      of maximal velocity of shortening/relengthening, prolongation of relengthening
      duration and intracellular Ca(2+) clearing time. Cell shortening at different
      extracellular Ca(2+) revealed stronger myocyte-shortening amplitude under lower
      (0.5 mM) Ca(2+) in CAT mice. Protein expression of NCX, RyR, Akt and pAkt were
      elevated in myocytes from CAT mice, while those of SERCA, PLB and DHPR were not
      affected. In conclusion, our data suggest that catalase overexpression may
      protect cardiac myocytes from ethanol-induced contractile defect, partially
      through improved intracellular Ca(2+) handling and Akt signaling.

PMID- 12788383
TI  - Acetylcholine-induced production of reactive oxygen species in adult rabbit
      ventricular myocytes is dependent on phosphatidylinositol 3- and Src-kinase
      activation and mitochondrial K(ATP) channel opening.
AB  - Acetylcholine (ACh), like ischemic preconditioning (PC), protects against
      infarction and is dependent on generation of reactive oxygen species (ROS). To
      investigate the mechanism by which ACh causes ROS production, isolated adult
      rabbit cardiomyocytes underwent a timed incubation in reduced MitoTracker Red,
      which is oxidized to a fluorescent form after exposure to ROS. The mitochondrial
      ATP-sensitive potassium (mK(ATP)) channel opener diazoxide (50 microM) increased
      fluorescence by 47 +/- 9% (P = 0.007), indicating that opening of mK(ATP) leads
      to ROS generation, and that increase was blocked by the mK(ATP) blocker 5
      hydroxydecanoate (5HD, 1 mM); 250 microM ACh caused a similar increase in ROS
      generation (+45 +/- 6% for all experiments, P < 0.001). ACh-induced ROS
      production was prevented by (1) blockade of muscarinic surface receptors with 100
      microM atropine (-6 +/- 2%, P = n.s.) or 250 nM 4-DAMP (+5 +/- 13%, P = n.s.),
      indicating that ACh's effect was receptor mediated; (2) closing K(ATP) channels
      with either the non-selective channel closer glibenclamide (50 microM) (-1.2 +/-
      17%, P = n.s.) or the selective mK(ATP) closer 5HD (-1.8 +/- 9%, P = n.s.),
      indicating that increased ROS production involved opening of mK(ATP); (3)
      blockade of mitochondrial electron transport chain with 200 nM myxothiazol (-4 +/
      9%, P = n.s.), indicating ROS came from the mitochondria; (4) addition of 100 nM
      wortmannin (-13 +/- 12%, P = n.s.), indicating that phosphatidylinositol 3-(PI3)
      kinase was involved; and (5) blockade of Src-kinase with 1 microM PP2 (-2 +/- 5%,
      P = n.s.), indicating the involvement of an Src-kinase. These results support the
      hypothesis that occupation of muscarinic surface receptors by ACh causes
      activation of PI3- and Src-kinases that then open mK(ATP) resulting in
      mitochondrial ROS generation and triggering of the preconditioned state.

PMID- 12788384
TI  - Long-term outcome of fetal cell transplantation on postinfarction ventricular
      remodeling and function.
AB  - OBJECTIVES: The purpose of this study was to determine the long-term outcome of
      fetal cell transplantation into myocardial infarction on left ventricular (LV)
      function and remodeling. BACKGROUND: While neonatal cell transplantation improved
      function for acute myocardial infarction, long-term data on the effects of cell
      transplant therapy using a more primitive cell on ventricular remodeling and
      function are needed.Methods. - Therefore, we injected 4 x 10(6) Fischer 344 fetal
      cardiac cells or medium into 1-week old infarcts in adult female Fischer rats to
      assess long-term outcome. RESULTS: Ten months after transplantation histologic
      analysis showed that cell implants were readily visible within the infarct scar.
      Infarct wall thickness was greater in cell-treated at 0.69 +/- 0.05 mm (n = 11)
      vs. medium-treated hearts at 0.33 +/- 0.01 mm (n = 19; P = 0.0001). Postmortem LV
      volume was 0.41 +/- 0.04 ml in cell-treated vs. 0.51 +/- 0.03 ml in medium
      treated hearts (P < 0.04). Ejection fraction assessed by LV angiography was 0.40
      +/- 0.02 in cell-treated (n = 16) vs. 0.33 +/- 0.02 in medium-treated hearts (n =
      24; P < 0.03) with trends towards smaller in vivo end-diastolic and end-systolic
      volumes in cell-treated vs. medium-treated hearts. Polymerase chain reaction
      analysis of the Sry gene of the Y chromosome was positive in four of five cell
      treated and zero of five medium-treated hearts confirming viability of male cells
      in female donors. CONCLUSION: Over the course of 10 months, fetal cardiac cell
      transplantation into infarcted hearts increased infarct wall thickness, reduced
      LV dilatation, and improved LV ejection fraction. Thus, fetal cell-transplant
      therapy mitigated the longer-term adverse effects of LV remodeling following a
      myocardial infarction.

PMID- 12788385
TI  - Focal complex formation in adult cardiomyocytes is accompanied by the activation
      of beta3 integrin and c-Src.
AB  - In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal
      assembly of c-Src and other signaling proteins which was partially mimicked in
      vitro using adult feline cardiomyocytes embedded in three-dimensional (3D)
      collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD)
      peptide. In the present study, we improved this model further to activate c-Src
      and obtain a full assembly of the focal adhesion complex (FAC), and characterized
      c-Src localization and integrin subtype(s) involved. RGD dose response
      experiments revealed that c-Src activation occurs subsequent to its cytoskeletal
      recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion
      kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine
      tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the
      expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src
      movement from the detergent-soluble to the -insoluble cytoskeletal fraction and
      (ii) confocal microscopic analysis showed c-Src movement from a
      nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused
      sarcolemmal co-localization of FAK and vinculin. Characterization of integrin
      subtypes revealed that beta3, but not beta1, integrin plays a predominant role:
      (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD
      stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD
      stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at
      Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data
      indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation
      and c-Src sarcolemmal localization, that subsequent c-Src activation is
      accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these
      events might be crucial for growth and remodeling of hypertrophying adult
      cardiomyocytes.

PMID- 12788387
TI  - Thioredoxin redox signaling in the ischemic heart: an insight with transgenic
      mice overexpressing Trx1.
AB  - This study examined if thioredoxin, the major redox-regulator in the mammalian
      system, plays any role in the redox signaling of ischemic myocardium. Isolated
      working rat hearts were made globally ischemic for 30 min followed by 2 h of
      reperfusion. Another group of hearts was rendered tolerant to ischemia by four
      cyclic episodes of 5 min ischemia each followed by another 10 min of reperfusion.
      Reperfusion of ischemic myocardium resulted in the downregulation of thioredoxin
      1 (Trx1) expression, which was upregulated in the adapted myocardium. The
      increased expression of Trx1 was completely blocked with cis-diammine
      dichloroplatinum (CDDP), an inhibitor of Trx1. CDDP also abolished
      cardioprotection afforded by ischemic adaptation as evidenced by a reduction of
      post-ischemic ventricular recovery, increase in myocardial infarct size and
      cardiomyocyte apoptosis. The decreased amount of reactive oxygen species in the
      adapted heart was increased significantly, when Trx1 was blocked with CDDP. The
      cardioprotective role of Trx1 was further confirmed with transgenic mouse hearts
      overexpressing Trx1. The Trx1 mouse hearts displayed significantly improved post
      ischemic ventricular recovery and reduced myocardial infarct size as compared to
      the corresponding wild-type mouse hearts. Taken together, the results of this
      study implicate a crucial role of Trx1 in redox signaling of the ischemic
      myocardium.

PMID- 12788386
TI  - Targeted deletion of caspase-1 reduces early mortality and left ventricular
      dilatation following myocardial infarction.
AB  - Objective. - Mice with targeted deletion of caspase-1 (interleukin-1beta (IL
      1beta)-converting enzyme) lack the active forms of IL-1beta and IL-18, two
      cytokines implicated in maladaptive ventricular remodeling following cardiac
      injury. We, therefore, investigated the extent of ventricular dilation in caspase
      1-knockout (KO) mice. Methods and results. - Transthoracic echocardiography was
      performed at days 1, 4, and 9 following left anterior descending artery ligation
      in caspase-1-KO and wild-type (WT) control animals, including M-mode and short
      axis imaging at both mid-papillary and apical levels. Although initial post
      operative mortality was lower in KO than in WT animals (21.4% WT, 12.0% KO, P <
      0.001), there was no difference in mortality between 24 h and 9 d (P = n.s.).
      Caspase-1 KOs exhibited significantly less mid-papillary ventricular dilatation
      at days 4 and 9 compared to day 1 post-myocardial infarction (MI) (P < 0.05).
      Caspase-1 KOs also had a marked (50%) reduction in the level of matrix
      metalloproteinase 3 (MMP-3), although no significant changes occurred in other
      MMPs or in tissue inhibitors of metalloproteinase 1 levels by immunoblot
      analysis. Although IL-beta plasma levels were not detectable, both IL-18 levels
      and the rate of apoptosis in remodeling, non-infarcted muscle were significantly
      higher in WT compared to caspase-1-KO animals.Conclusion. - Mice lacking caspase
      1 exhibited both improved peri-infarct survival and a decreased rate of
      ventricular dilatation, possibly due in part to a decrease in MMP-3 activity, IL
      18 production, and a reduction in the rate of apoptosis after experimental MI.

PMID- 12788388
TI  - Varying susceptibility to myocardial infarction among C57BL/6 mice of different
      genetic background.
AB  - Genetically manipulated mouse lines are invaluable to investigate the effects of
      a single gene on sensitivity to ischemia. When choosing appropriate controls, we
      were concerned that intrinsic, strain-independent but colony-dependent
      differences may influence the susceptibility to ischemia. We, therefore, compared
      the infarct:risk volume ratio (I:R%) after 30-min global ischemia in Langendorff
      perfused hearts from outbred C57BL/6 mice with that in wild-type mice derived
      from heterozygote x heterozygote crosses of two different in-house C57BL/6 mouse
      lines with targeted disruption of an MKK3 or MAPKAPK2 allele. Despite similar
      hemodynamic characteristics, I:R% in outbred C57BL/6 hearts was
      significantlysmaller (40.8 +/- 2.8%) than in C57BL/6 MAPKAPK2 wild types (65.8 +/
      4.5%, P = 0.0003) and significantly larger than in C57BL/6 MKK3 wild types (23.7
      +/- 2.9%, P = 0.002). Therefore, inherent colony substrain-dependent differences
      appear to influence the susceptibility to infarction in response to global
      ischemia, underscoring the importance of using colony-matched wild-type controls
      in murine studies of myocardial ischemia.

PMID- 12788389
TI  - More haste, less speed.

PMID- 12788390
TI  - The real value of microarray technology.

PMID- 12788391
TI  - The legacy of depleted uranium.

PMID- 12788394
TI  - New boost for Italian cancer research.

PMID- 12788396
TI  - New class of drugs help target NO to cancer cells.

PMID- 12788402
TI  - Second-line chemotherapy for ovarian cancer.

PMID- 12788404
TI  - Of mice and men.

PMID- 12788405
TI  - Amputation for soft-tissue sarcoma.
AB  - Soft-tissue sarcomas are a group of rare malignant tumours, many of which arise
      in the limbs. Most are treated with a combination of wide local excision and
      radiotherapy, but a small number--including proximal, large, high-grade, or
      recurrent tumours, or those involving major neurovascular structures--necessitate
      major amputation including forequarter or hindquarter amputation. These uncommon
      operations should remain in the surgical armamentarium for carefully selected
      patients. Those being considered for amputation should be referred to a tertiary
      sarcoma unit for examination of all other options, such as limb-salvage surgery,
      tumour downstaging with chemotherapy or radiotherapy (perhaps with subsequent
      limb-salvage surgery), or novel techniques such as isolated limb perfusion. Only
      after careful assessment should amputation be carried out. Outcomes after major
      amputation are highly variable, but such procedures can confer useful palliation
      to patients with distressing symptoms (pain, bleeding, fungation), long-term
      disease-free survival with reasonable function in carefully selected patients,
      and cure in some.

PMID- 12788406
TI  - Limb salvage in musculoskeletal oncology.
AB  - Since the early 1970s, substantial progress in dealing with musculoskeletal
      tumours has been made, with improvements in surgical skills, radiology,
      chemotherapy, pathology, and radiotherapy. Nowadays, 70-85% of all malignant
      tumours are treated by limb salvage, without compromising the oncological result.
      After many years, the functional result that may be achieved with a limb-saving
      procedure is becoming clear. Limb salvage has cosmetic advantages, but whether
      the quality of life of these patients is superior to that of those who undergo
      amputation is unclear. The non-oncological complication rate is much higher after
      limb salvage than after amputation, and consequently additional surgery is
      necessary. In the future, the co-operating disciplines should strive for better
      survival of these patients, for which the development of new chemotherapeutic
      drugs is especially needed.

PMID- 12788407
TI  - Relevance of DNA methylation in the management of cancer.
AB  - Many genetic and environmental factors contribute to development of cancer, but
      DNA methylation may provide a link between these influences. Genome stability and
      normal gene expression are largely maintained by a fixed and predetermined
      pattern of DNA methylation. In cancer, this idealistic scenario is disrupted by
      an interesting phenomenon: the hypermethylation of regulatory regions called CpG
      islands in some tumour suppressor genes--eg, BRCA1, hMLH1, p16INK4a, APC, VHL-
      which causes their inactivation. Development of new techniques that couple
      bisulphite modification with PCR has enabled these alterations to be studied in
      all types of biological fluids and archived tissues. Potentially, there are four
      types of translational studies that can be used to investigate the aberrant
      pattern of DNA methylation in cancer. First, CpG island hypermethylation can be
      used as a marker to identify cancer cells from biological samples, eg, serum and
      urine. This technique is highly sensitive and informative because profiles of
      tumour-suppressor-gene inactivation are specific to particular cancers. Second,
      single and combined genes that are inactivated by promoter hypermethylation, such
      as p16INK4a and DAPK, can be used as prognostic factors. Third, products of genes
      that are silenced by DNA methylation can be used as biomarkers of response to
      chemotherapy or hormone therapy--eg, the DNA repair O6-methylguanine-DNA
      methyltransferase and the oestrogen receptor. Finally, dormant tumour suppressor
      genes can be reactivated by DNA demethylating drugs, with the aim of reversing
      the neoplastic phenotype. These are new avenues worth exploring in the fight
      against cancer.

PMID- 12788408
TI  - Extraocular muscle palsy from metastatic prostate cancer.

PMID- 12788409
TI  - Isolated limb perfusion with melphalan in the treatment of malignant melanoma of
      the extremities: a systematic review of randomised controlled trials.
AB  - Isolated limb perfusion is a surgical procedure for delivering a high dose of
      chemotherapeutic or immunochemotherapeutic agent to a localised area, thus
      avoiding the severity of side-effects caused by systemic administration. This
      technique is generally used for treatment of patients with tumours of the limbs
      and extremities. We have done a systematic review of randomised controlled trials
      assessing the effectiveness of this treatment in patients with melanoma of the
      extremities. Four trials of 1038 patients met our inclusion criteria and were
      analysed. Although our analysis confirmed the reported increase in survival in
      two of the trials, neither had sufficient power to detect significant benefit for
      perfusion. Results from the trials showed that prophylactic perfusion has an
      equivocal effect on survival in patients with limb melanoma. Therefore, current
      evidence suggests that prophylactic isolated limb perfusion cannot be recommended
      as a routine adjunct to standard surgery in patients with high-risk primary limb
      melanoma, but only as a treatment for local disease control if other forms of
      locoregional therapy are not available.

PMID- 12788410
TI  - Methods for decreasing postoperative gut dysmotility.
AB  - Postoperative disturbances of gastrointestinal function (postoperative ileus) are
      among the most significant side-effects of abdominal surgery for cancer. Without
      specific treatment, major abdominal surgery causes a predictable gastrointestinal
      dysfunction which endures for 4-5 days and results in an average hospital stay of
      7-8 days. Ileus occurs because of initially absent and subsequently abnormal
      motor function of the stomach, small bowel, and colon. This disruption results in
      delayed transit of gastrointestinal content, intolerance of food, and gas
      retention. The aetiology of ileus is multifactorial, and includes autonomic
      neural dysfunction, inflammatory mediators, narcotics, gastrointestinal hormone
      disruptions, and anaesthetics. In the past, treatment has consisted of
      nasogastric suction, intravenous fluids, correction of electrolyte abnormalities,
      and observation. Currently, the most effective treatment is a multimodal
      approach. Median stays of 2-3 days after removal of all or part of the colon
      (colectomy) are now achievable. Recent discoveries have the potential to
      significantly reduce postoperative ileus in patients with cancer who have had
      abdominal surgery.

PMID- 12788411
TI  - Severe high-grade dysplasia and in-situ carcinoma of the common bile duct and
      pancreatic duct.

PMID- 12788412
TI  - Collet-Sicard syndrome--a report and review.

PMID- 12788413
TI  - Does amifostine have a role in chemoradiation treatment?
AB  - For many years, scientists have been investigating use of drugs to protect normal
      tissue from injury during radiation therapy, thereby increasing the amount of
      radiation that can be safely administered to patients. Despite the introduction
      of modern shielding techniques, dose modulation, and tissue-volume mapping, a
      small amount of normal tissue surrounding the target volume is inevitably
      irradiated during treatment, which can lead to severe side-effects. The most
      recent chemical radioprotector to become available clinically is amifostine. On
      the basis of efficacy data from a phase III randomised trial in patients with
      head and neck cancer, which showed reduced acute and chronic xerostomia with
      preserved antitumour response, some institutions are now adding amifostine to
      their chemoradiation regimens. However, much controversy surrounds the use of
      this drug. Some investigators are worried that radioprotectors may stop tumour
      tissue responding to radiation and therefore reduce treatment effectiveness.
      Moreover, amifostine opponents argue that the evidence is insufficient to justify
      routine use of this drug. In this Debate, David Brizel, who worked on the phase
      III amifostine efficacy study, and Jens Overgaard, a vehement opponent of
      amifostine therapy, provide thought-provoking arguments for two opposing
      perspectives on this contentious issue.

PMID- 12788418
TI  - Focused Assessment with Sonography for Trauma in weightlessness: a feasibility
      study.
AB  - BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examines for
      fluid in gravitationally dependent regions. There is no prior experience with
      this technique in weightlessness, such as on the International Space Station,
      where sonography is currently the only diagnostic imaging tool. STUDY DESIGN: A
      ground-based (1 g) porcine model for sonography was developed. We examined both
      the feasibility and the comparative performance of the FAST examination in
      parabolic flight. Sonographic detection and fluid behavior were evaluated in four
      animals during alternating weightlessness (0 g) and hypergravity (1.8 g) periods.
      During flight, boluses of fluid were incrementally introduced into the peritoneal
      cavity. Standardized sonographic windows were recorded. Postflight, the video
      recordings were divided into 169 20-second segments for subsequent interpretation
      by 12 blinded ultrasonography experts. Reviewers first decided whether a video
      segment was of sufficient diagnostic quality to analyze (determinate).
      Determinate segments were then analyzed as containing or not containing fluid. A
      probit regression model compared the probability of a positive fluid diagnosis to
      actual fluid levels (0 to 500 mL) under both 0-g and 1.8-g conditions. RESULTS:
      The in-flight sonographers found real-time scanning and interpretation
      technically similar to that of terrestrial conditions, as long as restraint was
      maintained. On blinded review, 80% of the recorded ultrasound segments were
      considered determinate. The best sensitivity for diagnosis in 0 g was found to be
      from the subhepatic space, with probability of a positive fluid diagnosis ranging
      from 9% (no fluid) to 51% (500 mL fluid). CONCLUSIONS: The FAST examination is
      technically feasible in weightlessness, and merits operational consideration for
      clinical contingencies in space.

PMID- 12788419
TI  - Prospective randomized trial of skin adhesive versus sutures for closure of 217
      laparoscopic port-site incisions.
AB  - BACKGROUND: The purpose of this study is to determine whether closure of
      laparoscopic port-site incisions using octylcyanoacrylate (OCA) is feasible,
      whether it is faster than traditional subcuticular suturing, whether the number
      and length of incisions impact on closure time, and to determine wound morbidity
      and patient satisfaction outcomes. STUDY DESIGN: A prospective randomized trial
      was performed on adult patients scheduled for elective laparoscopic surgery in
      three surgical specialties at a tertiary referral center. Patients were
      randomized to have closure of laparoscopic port sites using either OCA or
      sutures. Patients were followed up 2 to 3 weeks postoperatively. At 2 months
      patients were mailed a questionnaire regarding their satisfaction with the method
      of closure and the appearance of their scars. RESULTS: A total of 175 incisions
      in 50 patients were closed with OCA, and 142 incisions in 42 patients were closed
      with subcuticular sutures. Time to close was significantly faster for OCA (median
      2.5 minutes versus 6 minutes, p < 0.001). OCA was faster than traditional
      subcuticular suturing for cases involving three or more port sites (median 2.5
      minutes versus 6 minutes, p < 0.001), and for cases with total length of
      incisions >4 cm (median 2.6 minutes versus 7 minutes, p < 0.001). OCA and
      subcuticular suturing groups did not differ significantly on patient acceptance
      or assessment of scars. CONCLUSIONS: Closure of laparoscopic port-site incisions
      is feasible with OCA. Closure with OCA requires significantly less operative time
      than subcuticular suturing, particularly in cases when three or more port sites
      are used or when total incision length is greater than 4 cm. OCA appears to have
      equivalent adverse wound outcomes and patient acceptance rates as subcuticular
      suturing.

PMID- 12788421
TI  - Factors influencing delayed gastric emptying after pylorus-preserving
      pancreatoduodenectomy.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is the most frequent postoperative
      complication after pylorus-preserving pancreatoduodenectomy (PPPD). This study
      was undertaken to determine which factors influence the development of DGE after
      PPPD. STUDY DESIGN: We studied 150 consecutive patients who underwent PPPD
      performed by one surgeon between 1996 and 2000. The variables analyzed were age,
      gender, diagnosis, laboratory data, operative time, transfusion, preoperative
      cholangitis, and complications. The operative factors included were route of the
      afferent jejunal limb (retromesenteric versus antemesenteric), type of
      pancreatoenteric anastomosis, and preservation of the right gastric artery. DGE
      was defined as nasogastric drainage for more than 10 days or delay of regular
      diet until 14 days postoperatively. RESULTS: Univariate analysis showed
      preoperative cholangitis, intraabdominal complication, and the jejunal
      reconstruction method were significantly associated with DGE. Preservation of the
      right gastric artery was not associated with gastric emptying ability.
      Multivariate analysis by logistic regression showed that DGE was significantly
      more frequent among patients with preoperative cholangitis (15 of 36 [41.7%]
      versus 19 of 114 [16.7%], p=0.0031), postoperative intraabdominal complications
      (15 of 36 [41.7%] versus 10 of 114 [8.8%], p = 0.0001), and in the
      retromesenteric group (33 of 104 [31.7%] versus 3 of 46 [6.5%], p = 0.0174).
      CONCLUSIONS: Preoperative cholangitis and postoperative leakage problems affect
      gastric emptying after PPPD during the early postoperative period. The
      retromesenteric route is not recommended for pancreato- and biliary-enteric
      anastomosis. We speculate that retromesenteric passage of afferent jejunum can
      cause venous congestion and bowel edema, which can in turn retard the recovery of
      jejunal peristalsis at the duodenojejunostomy site resulting in disturbance from
      food passage.

PMID- 12788420
TI  - Spermatogenesis after parathyroidectomy in patients with symptomatic secondary
      hyperparathyroidism.
AB  - BACKGROUND: The changes in spermatogenesis after parathyroidectomy in patients
      with symptomatic secondary hyperparathyroidism have not been reported before.
      STUDY DESIGN: Nineteen men with symptomatic secondary hyperparathyrodism were
      enrolled in our study. Their ages ranged from 29 to 50 years and duration of
      dialysis from 72 to 168 months. Before operation, serum levels of calcium,
      phosphorus, alkaline phosphatase, intact parathyroid hormone, prolactin,
      luteinizing hormone, follicle-stimulating hormone, and testosterone were checked
      routinely in association with semen analysis. Those data were checked again 3
      months after successful operation. Finally, 15 patients had total
      parathyroidectomy with subcutaneous autotransplantation of 60 or 90 mg of tissue
      and complete postoperative data was available for 13 patients. The semen analysis
      included sperm density, volume of semen, motility index, percentage of active
      motility, and percentage of normal morphology. RESULTS: Ten patients had normal
      sperm density (> or =20 x 10(6)/mL), and nine patients had oligospermia (<20 x
      10(6)/mL) (n = 4) or azoospermia (n = 5). The ages of patients, duration of
      dialysis, and weight of removed parathyroid glands were quite similar between the
      two groups. The serum levels of calcium, phosphorus, alkaline phosphatase, intact
      parathyroid hormone, prolactin, luteinizing hormone, follicle-stimulating
      hormone, and testosterone were not significantly different between the group with
      normospermia and the group with oligospermia or azoospermia. Three months after
      total parathyroidectomy with autotransplantation, the serum levels of calcium,
      phosphorus, alkaline phosphatase, and intact parathyroid hormone were markedly
      decreased; the percentage of active motility and motility index were markedly
      improved; the serum levels of prolactin, luteinizing hormone, follicle
      stimulating hormone, and testosterone had no significant changes; and the volume
      of semen, sperm density, and percentage of normal morphology had no significant
      improvements. One patient, who had oligospermia with primary infertility, had
      paternity 6 months after parathyroidectomy, though his oligospermia remained
      unchanged at that time. CONCLUSION: After parathyroidectomy, the sperm motility
      index and percentage of active motility can be improved. We speculate that
      increases in fertilization and paternity in uremic male patients can be expected
      after surgery.

PMID- 12788422
TI  - Autopsy findings in patients after curative esophagectomy for esophageal
      carcinoma.
AB  - BACKGROUND: The mode of recurrence after esophagectomy for esophageal cancer has
      seldom been studied in detail from autopsy findings. STUDY DESIGN: We reviewed
      the autopsy findings in 43 curatively resected cases of esophageal cancer between
      1976 and 1997 at a single institution. RESULTS: Recurrent or residual esophageal
      cancer was identified in 27 of the 43 patients (62.8%) at autopsy. Local
      recurrence, lymph node metastases, hematogenous metastases, and serosal
      carcinomatosis were observed in 11 (25.6%), 18 (41.9%), 17 (39.5%), and 11
      patients (25.6%), respectively. Metastases to the thoracic, abdominal, and
      cervical nodes were observed in 37.2%, 16.3%, and 11.6% of the cases at autopsy,
      respectively. The pulmonary hilar nodes were most frequently involved (25.6%).
      The frequency of local recurrence was significantly lower in cases after curative
      subtotal esophagectomy with two- or three-field dissection (19.4%) than in cases
      after lower esophagectomy (66.7%) (p = 0.032). The frequency of hematogenous
      metastases after curative esophagectomy after preoperative radiotherapy was
      significantly lower in responders (Grades 2 to 3) than in nonresponders (Grades 0
      to 1) (p = 0.035). CONCLUSIONS: This study showed the characteristics of
      recurrence after esophagectomy for esophageal cancer. Despite esophagectomy with
      lymph node dissection, the frequency of each mode of recurrence was remarkably
      high. Anatomic difficulty of complete removal of lymph nodes by surgical
      procedures was suggested. Hematogenous metastases and serosal carcinomatosis were
      beyond surgical resection. More effective multimodal therapy will be required to
      improve survival of esophageal cancer patients.

PMID- 12788423
TI  - Colorectal adenocarcinoma in cirrhotic patients.
AB  - BACKGROUND: Colorectal carcinoma in cirrhotic patients is different from that in
      patients without the liver disease. The aims of this study were to evaluate the
      incidence of liver metastasis, postoperative mortality, and the predictors of
      longterm survival. STUDY DESIGN: A retrospective analysis of patients operated on
      for colorectal adenocarcinoma at the Mayo Clinic, Rochester, MN between 1976 and
      2001, with confirmed liver cirrhosis at the time of abdominal exploration.
      RESULTS: Seventy-two patients were available for analysis. They were 43% Child A,
      42% Child B, and 15% Child C. The median age was 70 (range 42 to 89) years, and
      the mean duration of followup was 46 months. Postoperative death was 13%. The
      risk factors were an elevated bilirubin (p = 0.01) and prolonged prothrombin time
      (p = 0.009). Seven patients (10%) developed liver metastases. For the whole group
      1-, 3-, and 5-year survival rates were 69%, 49%, and 35%, respectively. Child A
      patients had a significantly better survival rate than the combined group of
      Child B and C patients (p = 0.008). The risks for longterm survival were
      decreased albumin (p = 0.002) and prolonged prothrombin time (p < 0.001). TNM
      stage of the carcinoma provided no prognostic information (p = 0.51).
      CONCLUSIONS: Liver metastases from colorectal adenocarcinoma is infrequent (10%)
      in cirrhotic patients. The Child's classification, and not the TNM stage of the
      carcinoma, predicts the risk of postoperative death and longterm survival.

PMID- 12788425
TI  - Surgical treatment of hepatocellular cancer in the era of hepatic
      transplantation.
AB  - BACKGROUND: This study compares liver resection (LR) or transplantation (LTx) in
      an attempt to reevaluate the indications for treatment. STUDY DESIGN: One hundred
      fifty-four LRs and 121 LTxs performed from 1985 to 1999 were considered. Survival
      and recurrence rate, together with age, gender, liver disease, Child-Pugh
      classification, alpha-fetoprotein (AFP), tumor capsule, vascular invasion, size,
      number of nodules, histologic grade, and pTNM were considered. Followup was
      completed in all cases (mean +/- SD = 3.2 +/- 2.9 years). RESULTS: The 5- and 10
      year actuarial survival rates were 61.7% and 59.8% in LTx and 46.9% and 28.0% in
      LR (p = 0.08). Recurrence-free survival was 85.9% and 85.9%, respectively, in LTx
      and 42.8% and 30.7% in LR (p < 0.0001). In both groups, size, capsule, AFP,
      vascular invasion, grade, pTNM, Child-Pugh classification, and age were all
      significantly related to survival and cancer recurrence. pTNM, AFP, Child-Pugh
      classification, and age, in LR, and capsule, AFP, and viral cirrhosis, in LTx,
      were significant independent variables in Cox's regression model for survival.
      Only AFP, vascular invasion, and grade were significant in both groups for
      recurrence. CONCLUSIONS: LTx offers better recurrence freedom than LR, but
      longterm survival is not significantly different in the two series. A strict
      selection should be made to optimize graft allocation. Size and multifocality
      should not be considered absolute contraindications for LTx. AFP, vascular
      invasion, and grade are more likely to reflect the risk of recurrence of the
      disease. LR should be considered in patients who do not fulfill transplant
      criteria and also in some categories of patients with certain tumor
      characteristics (small resectable tumors in well-compensated cirrhosis).

PMID- 12788424
TI  - Retrorectal cyst: a rare tumor frequently misdiagnosed.
AB  - BACKGROUND: The rarity of retrorectal cysts and their nonspecific clinical
      presentations often lead to misdiagnoses and inappropriate operations. In recent
      years, several such patients have been referred to our institutions for
      evaluation and treatment of misdiagnosed retrorectal cysts. A review of these
      patients is presented. STUDY DESIGN: Medical records of the colorectal surgery
      divisions at two institutions were reviewed. Patients found to have previously
      misdiagnosed retrorectal cysts were identified. Preliminary diagnoses, radiologic
      examinations, operative procedures, and final diagnoses were obtained. RESULTS:
      Seven patients with retrorectal cysts who had been misdiagnosed before referral
      were identified. These patients had been treated for fistulae in ano, pilonidal
      cysts, perianal abscesses; psychogenic, lower back, posttraumatic, or postpartum
      pain, and proctalgia fugax before the correct diagnosis was made. Patients
      underwent an average of 4.1 operative procedures. Physical examination in
      combination with CT scanning made the correct diagnosis in all patients. All
      patients underwent successful resection through a parasacrococcygeal approach,
      and six of seven did not require coccygectomy. The resected tumors included four
      hamartomas, two epidermoid cysts, and one enteric duplication cyst. CONCLUSIONS:
      Retrorectal cysts are a rare entity that can be difficult to diagnose without a
      high index of clinical suspicion. A history of multiple unsuccessful procedures
      should alert the clinician to the diagnosis of retrorectal cyst. Once suspected,
      the correct diagnosis can be made with physical examination and a CT scan before
      a definitive surgical procedure.

PMID- 12788426
TI  - Expression of gastrin-releasing peptide receptors in endometrial cancer.
AB  - BACKGROUND: The Bombesin (BBS)-related peptide, gastrin-releasing peptide, and
      its cognate receptor are ectopically expressed by many cancers, in which they
      regulate tumor proliferation and metastasis. But, their role in endometrial
      cancers is unknown. The purpose of this study was to determine whether
      endometrial cancer cell lines express functional BBS receptors and to determine
      whether they were coupled to the regulation of vascular endothelial growth factor
      (VEGF-A) expression. STUDY DESIGN: Endometrial cancer cell lines (HEC-1A, KLE,
      and AN3CA) were cultured according to the recommendations of the American Tissue
      Culture Collection. Ishikawa cells were maintained in Dulbecco's modified Eagle's
      medium plus 10% fetal bovine serum. Before BBS treatment, all cell lines were
      placed in serum-free, phenol-free media for 24 hours. BBS-stimulated increases in
      intracellular Ca(2+) ([Ca(2+)]i) were used to assess functional BBS receptor
      status. VEGF-A mRNA expression was determined by Northern blotting. RESULTS: BBS
      (100 nM) stimulated an increase in [Ca(2+)]i in HEC-1A, Ishikawa, and KLE cells,
      indicating the presence of functional BBS receptors. This increase did not occur
      in AN3CA cells. BBS stimulated a time-dependent increase in VEGF-A mRNA
      expression in Ishikawa and KLE cells. Ishikawa cells exhibited a peak of VEGF-A
      mRNA expression between 8 and 12 hours with a partial decline by 24 hours. KLE
      cells showed a relatively small increase at 12 hours. In contrast, HEC-1A cells
      exhibited a high baseline level of VEGF-A mRNA expression and did not show a
      response to BBS. CONCLUSIONS: These data demonstrate that endometrial cancer cell
      lines express functional BBS receptors. In Ishikawa, KLE, and HEC-1A cells, BBS
      receptors are coupled to the regulation of VEGF-A mRNA expression.

PMID- 12788427
TI  - An Internet-based evaluation system for a surgical residency program.
AB  - BACKGROUND: Efficient and meaningful evaluation of performance is critical to the
      professional development of trainees in surgical residency programs. Current
      paper-based evaluation instruments have numerous limitations. We developed an
      Internet-based evaluation system to more rapidly and efficiently assess the
      experience of residents, faculty, and rotations. STUDY DESIGN: An on-line
      evaluation system was designed and implemented in October 1999. Custom
      evaluations were created for residents, faculty, and rotations. Evaluations were
      completed via the Internet site from remote locations with standard computers and
      standard Web browser software. Completed evaluations were automatically available
      on-line for review and data analysis. Data were analyzed by chi-square analysis
      with a probability value of less than 0.05 considered statistically significant.
      RESULTS: Compliance in completion of evaluations improved from 50% to 80% in the
      initial 6 months of implementation (p < 0.01) with the Web-based system. There
      was no significant difference between faculty and resident compliance. In
      evaluation of "ease of use," a total of 612 responses were received over this
      period with a total average score of 3.5 (5 point scale, 5 = strongly agree).
      Residents' opinions (average score, 3.69) were slightly more positive than those
      of faculty (average score, 3.31). Confidentiality was improved over paper-based
      systems by a detailed security network. CONCLUSIONS: This Internet-based
      evaluation system is a potentially powerful instrument for evaluating our
      surgical residency program and making changes to improve the educational
      experience in a timely and efficient manner.

PMID- 12788428
TI  - "To Err Is Human": uniformly reporting medical errors and near misses, a naive,
      costly, and misdirected goal.

PMID- 12788429
TI  - What's new in neurological surgery.

PMID- 12788430
TI  - What's new in general surgery: surgical oncology.

PMID- 12788431
TI  - Surgical competence and surgical proficiency: definitions, taxonomy, and metrics.

PMID- 12788432
TI  - Who oversees innovative practice? Is there a structure that meets the monitoring
      needs of new techniques?

PMID- 12788434
TI  - An evidence-based approach to the surgical management of resectable pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Randomized prospective trials have addressed various treatment
      approaches to pancreatic adenocarcinoma in order to improve on the dismal
      prognosis associated with this disease. We conducted a comprehensive review of
      prospective randomized clinical trials and summarized the contemporary treatment
      of resectable pancreatic carcinoma. STUDY DESIGN: A literature search strategy
      identified prospective randomized clinical trials for pancreatic carcinoma using
      standard medical subject heading terms. The articles were critically reviewed and
      ranked according to a standardized three-tiered system (Ia, Ib, Ic) by a panel of
      experts. RESULTS: Surgical studies have demonstrated that morbidity and mortality
      are similar for pylorus-preserving and classic pancreaticoduodenectomy. Extended
      retroperitoneal lymphadenectomy can be performed with similar mortality but
      increased morbidity compared with standard pancreaticoduodenectomy but does not
      prolong survival. Pancreaticogastrostomy and pancreaticojejunostomy appear to be
      comparable techniques for pancreatic duct reconstruction. Pancreatic-enteric
      anastomosis is associated with lower rates of pancreatic fistula and endocrine
      insufficiency than duct occlusion without anastomosis. Intraperitoneal drainage
      after pancreatic resection is unwarranted and may contribute to intraabdominal
      complications. Routine use of prophylactic octreotide does not lower the rate of
      pancreatic fistula; it should be considered for reoperative pancreatic resection
      or for a soft gland. Early trials found that adjuvant chemoradiation therapy
      prolongs survival. But in more recent studies chemoradiation after resection has
      failed to show a survival advantage over surgery alone. CONCLUSIONS: Surgical
      resection remains the only potentially curative therapy for adenocarcinoma of the
      pancreas. There is no clear indication as to a single preferable resection
      approach.

PMID- 12788435
TI  - Laparoscopic staging of gastric cancer: an overview.

PMID- 12788436
TI  - Families' perceptions of surgical intensive care.

PMID- 12788437
TI  - Multiple gastric carcinoids.

PMID- 12788438
TI  - Midgut volvulus.

PMID- 12788439
TI  - A safe laparoscopic technique for the repair of inguinal hernias in boys.

PMID- 12788440
TI  - Endoscopic neck surgery with lymph node dissection for papillary carcinoma of the
      thyroid using a totally gasless anterior neck skin lifting method.

PMID- 12788441
TI  - Impact of culture on the patient-surgeon relationship.

PMID- 12788443
TI  - Abdominal pain analgesia.

PMID- 12788446
TI  - Ab initio prediction of the vibrational spectrum of the hydrogen bonded complex
      O2N...HONO2.
AB  - The changes in the structural parameters and vibrational characteristics
      (vibrational frequencies, infrared intensities and Raman activities) arising from
      the hydrogen bonding between NO(2) and HONO(2) have been studied employing ab
      initio 6-31G(d, p)/UHF and 6-31+G(d, p)/UHF, and B3LYP/6-31G(d, p) calculations.
      The charge rearrangement upon hydrogen bonding have been, estimated using the
      Mulliken population analyses. It was established that the complexation between
      NO(2) and HONO(2) leads to changes in the structural parameters and the
      vibrational characteristics of the monomers. The most sensitive to the hydrogen
      bond formation are the vibrational characteristics of the normal modes of the
      monomer bonds participating in the hydrogen bonding. The predicted shifts in the
      vibrational frequencies by ab initio and B3LYP/6-31G(d, p) calculations are in
      very good agreement with the experimentally observed, which is an evidence for
      the reliance of the studied structure.

PMID- 12788447
TI  - Fourier-transform Raman and infrared spectroscopic analysis of 2-nitro
      tetraphenylporphyrin and metallo-2-nitro-tetraphenylporphyrins.
AB  - The Fourier-transform Raman (FT-Raman) and infrared (FT-IR) spectra of 2-nitro
      tetraphenylporphyrin (2-NO(2)-TPP), nickel-2-nitro-tetraphenylporphyrin (Ni-2
      NO(2)-TPP), zinc-2-nitro-tetraphenylporphyrin (Zn-2-NO(2)-TPP) and copper-2-nitro
      tetraphenylporphyrin (Cu-2-NO(2)-TPP) were acquired for the first time and
      carefully assigned and discussed. The effects of a beta-NO(2) group and the
      influence of the central metal on the molecular symmetry and vibrational spectra
      of the porphyrin macrocycle were also examined. The bands at 1323-1339, 1516-1526
      and 961-971 cm(-1) were attributed to the symmetric and asymmetric stretching
      vibration of the NO(2) group and to the stretching vibration of the C(beta)-N
      bond, respectively, which connects the NO(2) group with the beta-carbon of the
      porphyrin macrocycle. These bands can act as a marker to distinguish beta-NO(2)
      TPPs from other beta-substituent TPPs. Cu-2-NO(2)-TPP has a C(4nu) molecular
      symmetry, which is different from those of Ni-2-NO(2)-TPP and Zn-2-NO(2)-TPP,
      i.e. D(4h).

PMID- 12788448
TI  - In situ UV-visible spectroelectrochemical evidences for conducting copolymer
      formation between diphenylamine and m-methoxyaniline.
AB  - Electrochemical copolymerization of diphenylamine (DPA) with m-methoxy aniline
      (MA) was carried out in 4 M H(2)SO(4) by cyclic voltammetry (CV). Cyclic
      voltammograms (CVs) of the copolymer films were recorded in monomer-free
      background electrolyte. In situ sepectroelectrochemical studies were carried out
      on an optically transparent electrode (Indium tin oxide (ITO) coated glass) in 4
      M H(2)SO(4) for different feed ratios of the comonomers. Constant potential and
      potential sweep methods were employed for performing polymerization. UV-visible
      absorption spectra were collected continuously and concurrently during the
      copolymerization in both the cases. The results from constant potential
      electropolymerisation indicated the formation of an intermediate with an
      absorption peak at 576 nm. Derivative cyclic voltabsorptogram (DCVA) was deduced
      from the results of cyclic spectrovoltammetry. The DCVA derived at 576 nm
      confirms the intermediates formed during the electrochemical copolymerization.
      The compositional changes of the two monomers in the copolymers with changes in
      feed composition of two monomers as predicted from in situ spectro
      electrochemical studies are evident from elemental analysis. A plausible
      copolymerization mechanism is suggested.

PMID- 12788450
TI  - Conformational structures and vibrational spectra of isolated pyrimidine
      nucleosides: Fourier transform infrared matrix isolation study of 2-deoxyuridine.
AB  - The conformational structures of 2-deoxyuridine (dU) were investigated using
      Fourier transform infrared (FTIR) matrix isolation spectroscopy. For the first
      time the FTIR spectra of dU in Ar matrices were obtained in the range 4000-200
      cm(-1). The stabilities of conformers were estimated by the methods HF/3-21G (p),
      HF/6-31G (d,p) and MP2/6-31G (d,p). Ab initio calculations of the infrared
      spectra were performed by the methods HF/3-21G (p) and HF/6-31G (d,p). The actual
      occupancy of conformational isomers in matrix samples was determined. It was
      shown that anti-conformers of dU are dominant. The ribose rings of the main anti
      conformers dU _a0, dU _a1 are in the C2'-endo conformation, but the ribose rings
      of minor anti-conformers dU_a2, dU_a3 have the C3'-endo conformation, stabilized
      by intramolecular hydrogen bonds O3'H...O5' and O5'H...O3', accordingly. Syn
      conformers of dU are stabilized by the intramolecular hydrogen bond O5'H...O2 and
      the dominant conformation of the ribose ring is C2'-endo.

PMID- 12788449
TI  - Angle-resolved soft X-ray emission and absorption spectroscopy of hexagonal boron
      nitride.
AB  - Angle-resolved soft X-ray emission and absorption spectra in the BK and NK
      regions of hexagonal BN were measured using polarized synchrotron radiation. The
      take-off/incident-angle-dependence on the spectral features in both X-ray
      emission and absorption is clearly observed. The configuration of the sigma and
      pi orbitals, which were calculated using discrete variational (DV)-Xalpha
      molecular orbital calculations, explains the angle-resolved soft X-ray emission
      and absorption spectra. The relative peak intensity of the 394-eV peak in the NK
      X-ray emission provides useful information about the BN layer ordering.

PMID- 12788451
TI  - Conformational polymorphism of solid tetramesityldisilene Mes2Si=SiMes2 (Raman,
      UV-vis, IR and fluorescence study).
AB  - Conformational polymorphism of solid tetramesityldisilene (1) has been studied by
      the methods of optical spectroscopy. The three known modifications of 1: orange
      unsolvated 1a and two 1:1 solvates with toluene (1b) and THF (1c) have been found
      to transform under specific conditions to a new, most thermodynamically stable
      polymorph, yellow unsolvated powder 1d. The latter has been characterized by the
      Raman, IR, UV-vis and fluorescence data. All forms of 1 exhibit Raman spectra
      differing in details, which reflect their different crystal and molecular
      structures. Unsolvated 1a and 1d differ significantly in electronic absorption
      and fluorescence emission. The yellow form 1d can be converted to the orange form
      1a upon illumination with laser light in the region 514-457 nm. Similarity of the
      Raman and UV-vis spectra of 1d to those of the solutions of 1 provides some
      evidence for a quasi-trans conformation of 1d.

PMID- 12788452
TI  - Infrared matrix isolation study of the 1:1 molecular complex of OVCl3 with
      (CH3)2O.
AB  - The 1:1 complex of OVCl(3) with (CH(3))(2)O has been isolated in argon matrices
      at 14 K, and characterized by infrared spectroscopy. The complex is relatively
      strongly bound, with significant shifts to vibrational modes of both the acid and
      base subunits in the complex. For example, the OC(2) symmetric stretch of
      (CH(3))(2)O shifted from 925 to 891 cm(-1) upon complex formation, while the
      VCl(3) antisymmetric stretching mode shifted from 505 to 474 cm(-1). Product
      identification and band assignments were confirmed by isotopic labeling. Attempts
      to convert the initial 1:1 complex into secondary intermediates by either thermal
      or photochemical processes were unsuccessful, suggesting that an active hydrogen
      atom is a key element in determining the pathway for reactions of OVCl(3).

PMID- 12788453
TI  - Equilibria of mononuclear oxomolybdenum(VI) complexes of triethanolamine. A
      multinuclear dynamic magnetic resonance study of structure and exchange
      mechanisms.
AB  - 1D and 2D 1H and 13C NMR spectra of the assumed [MoO(4)(TEA)](2-) complex
      recorded in DMSO at variable temperatures clearly indicate one free and two bound
      hydroxyethyl arms. The free arm of the ligand readily exchanges with the two
      metal-bound arms. Under such conditions the triethanolamine (TEA) acts as a
      bidentate ligand. The presence of water accelerates the exchange, which at higher
      water content involves the free ligand too. In organic solvents the binding
      strength of the hydroxo groups to the molybdenum is weaker than that of the water
      molecules. A plausible structure is confirmed by 14N, 17O and 95Mo measurements
      and an exchange mechanism based on the existence of an eight-membered relatively
      rigid chelate ring is suggested.

PMID- 12788454
TI  - A coupled-cluster study of the structure and vibrational spectra of pyrazole and
      imidazole.
AB  - Harmonic force fields were calculated at the corresponding optimized geometries
      for pyrazole and imidazole at the HF, B3LYP, MP2, CCSD and CCSD(T) levels using
      the 6-31G* basis set and at the HF and B3LYP levels using the cc-pVTZ basis set.
      The agreement between the calculated and experimental geometries by the CCSD and
      CCSD(T) methods was generally similar to that obtained with the B3LYP and MP2
      methods. The force fields were scaled using one-scale-factor (1SF), 3SF and 7SF
      scaling schemes. The scale factors were varied with respect to the experimental
      frequencies. Using 7SF scaling, the root-mean-square (RMS) deviation of the
      calculated frequencies from the experimental frequencies by the HF, B3LYP, MP2,
      CCSD and CCSD(T) methods and the 6-31G* basis set was 16, 7, 13, 11 and 11 cm(
      1), respectively. This shows that the B3LYP method is preferred for force field
      calculations over the perturbative MP2, CCSD and CCSD(T) methods. Using 1SF
      scaling, the CCSD(T) scale factor was 0.931, the highest among the five methods
      used but close to that obtained with the B3LYP method and the cc-pVTZ basis set
      with lower RMS deviation.

PMID- 12788455
TI  - On some characteristic properties of ATR liquid light conductors.
AB  - Electronic spectra of aqueous solutions of the malachite green dye have been
      measured by liquid and solid spectroscopy. Particular characteristics of the
      light conductor itself have been shown to have no considerable effect on the
      results of the experiment.

PMID- 12788456
TI  - Synthesis and characterization of novel dipeptide ester prodrugs of acyclovir.
AB  - Four dipeptide (Gly-Gly, Gly-Val, Val-Val, Val-Gly) ester prodrugs of 9-[(2
      hydroxyethoxy)methyl]guanine (acyclovir, ACV) were synthesized. LC/MS was used to
      characterize the new prodrugs. Both 1H NMR and 13C NMR spectra of the four
      prodrugs of ACV were measured and assigned based on spectral comparison with
      compounds of similar structures.

PMID- 12788458
TI  - Vibrational frequencies and structural determinations of 1,5-dicarba-closo
      pentaborane(5).
AB  - The normal mode frequencies and corresponding vibrational assignments of 1,5
      dicarba-closo-pentaborane(5) are examined theoretically using the GAUSSIAN 98 set
      of quantum chemistry codes. All normal modes were successfully assigned to one of
      six types of motion predicted by a group theoretical analysis (C-H stretch, B-H
      stretch, B-B stretch, B-C stretch, C-H wag, and B-H wag) utilizing the D(3h)
      symmetry of the molecule. By comparing the vibrational frequencies with IR and
      Raman spectra available in the literature, a set of scaling factors is derived.
      Theoretical IR and Raman intensities are reported.

PMID- 12788457
TI  - Study on the optical properties of 4,4'-bis-(2-(substituted-styryl))biphenyl and
      1,4-bis-(2-(substituted-styryl))benzene.
AB  - The maximum absorption wavelengths (lambda(a-max)), absorption coefficient
      (epsilon), maximum emission wavelengths (lambda(e-max)), fluorescent quantum
      yields (phi(f)), and second-order nonlinear polarizations (beta(xxx)) of
      seventeen 4,4'-bis-(2-(substituted-styryl))biphenyl and three 1,4-bis-(2
      (substituted-styryl))benzene were measured. The results showed that some of this
      series of compounds possess high fluorescent quantum yields in DMF, such as, 2
      (0.801), 3 (0.680), 5 (0.565), 15 (0.538) 16 (0.848), 18 (2.175), 19 (1.314) and
      20 (1.060), as compared with quinine-sulfuric acid. They could be used as
      fluorescent whiteners and fluorescent colorants. Some of these compounds were of
      a high beta(xxx) values, such as in DMSO, 2 (29.00/10(-30) m(5)c(-1)), 3
      (25.29/10(-30) m(5)c(-1)), 8 (21.79/10(-30) m(5)c(-1)) and 9 (24.08/10(-30)
      m(5)c(-1)). Electron-withdrawing substituent NO(2), which is attached to the two
      terminal phenyl rings could cause lambda(a-max) obviously to be shorter, but it
      made lambda(e-max) change longer. Electron-donating substituent at two end
      benzene rings, such as OCH(3), N((CH(3))(2)), even Cl, could make lambda(a-max)
      and lambda(e-max) longer, and the larger the electron-donating ability of the
      substituent, the longer the lambda(a-max) and lambda(e-max). This influence of 4
      position substituent on lambda(a-max) or lambda(e-max) is obviously larger than
      that of 2-position substituent, and the action of substituent on 2-position is
      larger than that of substituent on 3-position. The values of lambda(a-max) and
      lambda(e-max) of biphenyl compounds 2 or 3 were respectively close to these
      values of corresponding benzene compounds 18 or 19.

PMID- 12788459
TI  - Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl, and
      trimethylgermyl derivatives of 3,3-dimethylcyclopropene III. 3,3-Dimethyl-1
      (trimethylsilyl)cyclopropene.
AB  - The experimental Raman and IR vibrational spectra of 3,3-dimethyl-1
      (trimethylsilyl)cyclopropene in the liquid phase were recorded. Total geometry
      optimisation was carried out at the HF/6-31G* level and the HF/6-31G*//HF/6-31G*
      force field was computed. This force field was corrected by scale factors
      determined previously (using Pulay's method) for correction of the HF/6
      31G*//HF/6-31G* force fields of 3,3-dimethylbutene-1, 1-methyl-, 1,2-dimethyl-,
      and 3,3-dimethylcyclopropene. The theoretical vibrational frequencies calculated
      from the scaled quantum mechanical force field and the theoretical intensities
      obtained from the quantum mechanical calculation were used to construct predicted
      spectra and to perform the vibrational analysis of the experimental spectra.

PMID- 12788460
TI  - Study on vitamin K3-cyclodextrin inclusion complex and analytical application.
AB  - The inclusion interaction of the complexes between Vitamin K(3) (VK(3)) and beta
      cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and
      sulfobutylether-beta-cyclodextrin (SBE-beta-CD) were studied by using steady
      state fluorescence measurements. The various factors affecting the inclusion
      process were examined in detail. The formation constants and inclusion
      stoichiometry for VK(3)-CDs were determined. The results showed that the
      inclusion ability of beta-CD and its derivatives was the order: SBE-beta-CD>HP
      beta-CD>beta-CD. The related inclusion mechanism is proposed to explain the
      inclusion process. A method of determining VK(3) was established with the linear
      range was 2.5 x 10(-6)-5.0 x 10(-4) M, and was used to determine the VK(3)
      tablets. The recoveries were in the range of 97.52-103.5%. The results were
      satisfactory.

PMID- 12788461
TI  - Determination of trace tin by solid substrate-room temperature phosphorimetry
      using sodium dodecyl sulfate as sensitizer.
AB  - The effects of different surfactants on solid substrate-room temperature
      phosphorescence (SS-RTP) properties of Sn(4+)-morin systems were investigated. It
      was found that the SS-RTP intensity of luminescence system was increased greatly
      in presence of sodium dodecyl sulfate (SDS). A new highly sensitive method for
      the determination of trace tin has been proposed based on sensitization of SDS on
      SS-RTP intensity of morin-tin system on the filter paper substrate. The linear
      dynamic range of this method is 8.0-112 ag per spot (with the volume of 0.4
      microl per spot) with a detection limit of 4.0 ag per spot, and the regression
      equation is DeltaIp=199.7+3.456m(Sn(IV)) (ag per spot), with the correlation
      coefficient r=0.9998 (n=7). This simple, rapid and reproducible method has been
      applied to determine the amount of tin in real samples with satisfactory results.

PMID- 12788462
TI  - Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl, and
      trimethylgermyl derivatives of 3,3-dimethylcyclopropene II. 3,3-Dimethyl-1,2
      bis(trimethylsilyl)cyclopropene.
AB  - The IR and Raman spectra of 3,3-dimethyl-1,2-bis(trimethylsilyl)cyclopropene (I)
      (synthesised using standard procedures) were measured in the liquid phase. Total
      geometry optimisation was performed at the HF/6-31G* level. The HF/6-31G*//HF/6
      31G* quantum mechanical force field (QMFF) was calculated and used to determine
      the theoretical fundamental vibrational frequencies, their predicted IR
      intensities, Raman activities, and Raman depolarisation ratios. Using Pulay's
      scaling method and the theoretical molecular geometry, the QMFF of I was scaled
      by a set of scaling factors used previously for 3,3-dimethyl-1,2-bis(tert
      butyl)cyclopropene (17 scale factors for a 105-dimensional problem). The scaled
      QMFF obtained was used to solve the vibrational problem. The quantum mechanical
      values of the Raman activities were converted to differential Raman cross
      sections. The figures for the experimental and theoretical Raman and IR spectra
      are presented. Assignments of the experimental vibrational spectra of I are
      given. They take into account the calculated potential energy distribution and
      the correlation between the estimations of the experimental IR and Raman
      intensities and Raman depolarisation ratios and the corresponding theoretical
      values (including Raman cross sections) calculated using the unscaled QMFF.

PMID- 12788463
TI  - Spectra and structure of silicon-containing compounds. Part XXXVIII: Infrared and
      Raman spectra, vibrational assignment, conformational stability, and ab initio
      calculations of vinyldifluorosilane.
AB  - Infrared spectra (3500-50 cm(-1)) of gaseous and solid, and Raman spectrum (3500
      30 cm(-1)) of liquid vinyldifluorosilane, CH(2)z.dbnd6;CHSiF(2)H, are reported.
      Both the cis and gauche rotamers have been identified in the fluid phases. From
      temperature-dependent FT-infrared spectra of krypton solutions, it is shown that
      the cis conformer is more stable than the gauche form by 119+/-12 cm(-1) (1.42+/
      0.14 kJ mol(-1)). At ambient temperature there is 53+/-2% of the gauche conformer
      present. Complete vibrational assignments are provided for the cis conformer and
      several modes are identified for the gauche form. Harmonic force constants,
      fundamental frequencies, infrared intensities, and Raman activities have been
      obtained from MP2/6-31G(d) calculations with full electron correlation. The
      optimized geometries and conformational stabilities have also been obtained from
      ab initio MP2/6-31G(d), MP2/6-311+G(d,p), and MP2/6-311+G(2d,2p) calculations
      with full electron correlation as well as from density functional theory
      calculations (DFT) by the B3LYP method. The SiH bond distances (r(0)) of 1.472
      and 1.471 A have been obtained for the cis and gauche conformers, respectively,
      from the silicon-hydrogen stretching frequencies. These results are compared to
      the corresponding quantities of the corresponding carbon analogue as well as with
      some similar molecules.

PMID- 12788464
TI  - Optical and EPR studies of iron bearing phosphate minerals: satterlyite and
      gormanite from Yukon Territory, Canada.
AB  - The iron phosphate minerals satterlyite and gormanite have been investigated by
      EPR and optical absorption studies. The optical results indicate the presence of
      ferrous and ferric ions in both minerals. In gormanite the site symmetry of
      Fe(III) is near octahedral whereas in satterlyite it is tetragonally distorted.
      On the other hand, the Fe(II) ions are in tetragonally distorted octahedral site
      in both minerals. In satterlyite the EPR results indicate the presence of the
      ferric ion in a tetragonally distorted state together with a small percentage of
      Mn(II). Crystal field (Dq) and interelectronic parameters (B and C) are
      evaluated.

PMID- 12788465
TI  - Optosensing behavior of the first Ru(II)-compound of di-2-pyridylketone-p
      nitrophenylhydrazone (dpknph), [Ru(bpy)2(dpknph)]Cl2.
AB  - The reaction between Ru(bpy)(2)Cl(2) (bpy=2,2'-bipyridine) and di-2-pyridylketone
      p-nitrophenylhydrazone (dpknph) in refluxing ethanol gave
      [Ru(bpy)(2)(dpknph)]Cl(2) in good yield. Optical measurements on
      [Ru(bpy)(2)(dpknph)]Cl(2) in non-aqueous media revealed the presence of two
      interlocked electronic states due to conformational changes associated with the
      hydrazone moiety of [Ru(bpy)(2)(dpknph)]Cl(2). The equilibrium distribution of
      the high-energy beta-conformation associated with the high-energy electronic
      state and the low-energy alpha-conformation associated with the low-energy
      electronic state is solvent and solute dependent controlled by the solvent-solute
      and solute-solute interactions. The interplay between the alpha- and beta
      conformations of [Ru(bpy)(2)(dpknph)]Cl(2) allowed calculations of the extinction
      coefficients of electronic states by forcing the equilibrium to shift to one
      conformation using chemical stimuli. Extinction coefficients of 56000+/-2000 and
      48500+/-2000 M(-1) cm(-1) were calculated in DMSO for the beta- and alpha
      conformations of [Ru(bpy)(2)(dpknph)]Cl(2), respectively, using excess HgCl(2) in
      DMSO. Thermo-optical measurements on [Ru(bpy)(2)(dpknph)]Cl(2) in DMSO confirmed
      the interconversion between the alpha- and beta-conformations of
      [Ru(bpy)(2)(dpknph)]Cl(2) and gave changes in enthalpy (DeltaH(o)) of -35.5+/-4.0
      and 13.0+/-0.5 kJ mol(-1), entropy (DeltaS(o)) of -126.9+/-20 and 45.2+/-4.5 kJ
      mol(-1), and free energy (DeltaG(o)) of 2.31+/-0.2 and -0.48+/-0.2 kJ mol(-1) in
      the absence and presence of NaBH(4) at 295 K. The high values for the extinction
      coefficients and low values and sensitivity of the activation parameters for the
      interconversion between the alpha- and beta-conformations of
      [Ru(bpy)(2)(dpknph)]Cl(2) in DMSO to solution composition allowed for the use of
      this system ([Ru(bpy)(2)(dpknph)]Cl(2) and surrounding solvent or solute
      molecules) as a spectrophotometric sensor for a variety of chemical stimuli that
      include metal ions. Group 12 metal ions in concentrations as low as 1.00x10(-8) M
      can be detected and determined using [Ru(bpy)(2)(dpknph)]Cl(2) in DMSO in the
      presence and absence of NaBH(4).

PMID- 12788466
TI  - Liquid crystalline properties and IR spectra of 2'-hydroxy-4'
      octyloxyazobenzenes.
AB  - New azobenzene derivatives, namely 3,5-dichloro, 2,6-dimethyl and 3-chloro-4
      methyl derivatives of 2'-hydroxy-4'-octyloxyazobenzene were synthesized and their
      properties were compared with those of 4-chloro, 4-methyl and 4-nitroderivatives.
      Special attention was paid to the characteristics of intramolecular O-H...N
      hydrogen bond reflected in IR spectra of CCl(4) solutions and neat crystalline
      samples. The spectra were analyzed based on DFT calculations. In all cases of
      solutions very strong hydrogen bonds are manifested in broad bands centered at
      about 2700-2800 cm(-1) of low intensity typical of resonance assisted H-bonds. On
      the other hand, in cases of neat crystalline samples, a broad, intensified
      absorption is extended down to approximately 600 cm(-1) forming a continuum
      resembling a Hadzi's trio. However, neither broad maxima nor minima can be
      assigned to delta(OH) or gamma(OH) overtones. The studies of the H/D isotope
      effect on the continuum seem to indicate on the role of resonance couplings
      between nu(OH) vibrators of neighboring molecules as well as hot bands arising
      from the coupling between high and low frequency modes. These couplings modify
      the dynamic pattern of the potential for the proton motion leading to a decrease
      of the barrier for the proton transfer.

PMID- 12788467
TI  - An infrared study of CO adsorption on silica-supported Ru-Sn catalysts.
AB  - CO adsorption on Ru-Sn/SiO(2) catalysts of various Sn/(Ru+Sn) ratios was examined
      by Diffuse Reflectance Infrared Fourier-Transform Spectroscopy (DRIFTS). The
      catalysts were prepared by the incipient wetness impregnation method. Catalysts
      were activated by H(2) reduction at 773 K. CO adsorbed on the catalysts shows
      spectra whose band frequencies are divided into three groups: (i) High Frequency
      Region (HFR), containing a band at 2065 cm(-1), (ii) Low Frequency Region 1
      (LFR(1)), containing bands at 2040-2015 cm(-1), (iii) Low Frequency Region 2
      (LFR(2)), containing bands at 1990 and 1945 cm(-1). The types of adsorbed CO
      species formed strongly depend on the ratio Sn/(Ru+Sn) in the catalyst, CO
      pressure and temperature of adsorption. Adsorption of CO on Ru sites in the
      Ru/SiO(2) catalyst results in LFR(1) bands at 2040-2015 cm(-1), which are
      independent of the CO pressure but the adsorption complexes are easily destroyed
      by raising the temperature. The addition of Sn to the catalyst creates new sites
      for CO adsorption. After adsorption at 298 K, the HFR band at 2065 cm(-1) and
      LFR(2) bands at 1990-1950 cm(-1) are observed. The relative intensities of these
      bands increase with increasing Sn-content in the samples. The LFR bands are
      thermally stable while the HFR band is not. The formation of the corresponding
      species is favored by increasing the CO pressure. Adsorbed CO species giving
      LFR(1) bands are assigned to linearly-adsorbed CO on the Ru(0) and/or on the Ru
      Sn alloy sites. Adsorbed CO species giving HFR bands are assigned to CO
      adsorption on Ru(delta+)-O-Sn sites. After low temperature CO adsorption on
      samples with high Sn-content, only species that show bands at 1990 and 1945 cm(
      1) in LFR(2) are observed.

PMID- 12788468
TI  - Spectra and structure of silicon containing compounds. XXXIX. Raman and infrared
      spectra, conformational stability, vibrational assignment and ab initio
      calculations of n-propyltrifluorosilane.
AB  - The infrared (3100-40 cm(-1)) spectra of gaseous and solid and Raman (3200-20 cm(
      1)) spectra of liquid with qualitative depolarization values and solid n
      propyltrifluorosilane, CH(3)CH(2)CH(2)SiF(3), have been recorded. Additionally
      the infrared spectra of the sample in nitrogen and argon matrices have been
      recorded. Both the anti and gauche conformers have been identified in the fluid
      phases but only the anti conformer remains in the solid. Variable temperature (
      105 to -150 degrees C) studies of the infrared spectra of the sample dissolved in
      liquid krypton have been recorded and the enthalpy difference has been determined
      to be 135+/-14 cm(-1) (1.62+/-0.17 kJ mol(-1)) with the anti conformer the more
      stable form. At ambient temperature it is estimated that there is 51+/-2% of the
      gauche conformer present. Also the enthalpy difference in the liquid was obtained
      from variable temperature studies of the Raman spectra and from three conformer
      pairs an average value of 179+/-18 cm(-1) (2.14+/-0.22 kJ mol(-1)) was obtained
      again with the anti form the more stable conformer. Relatively complete
      vibrational assignments are proposed for both conformers based on the relative
      infrared and Raman spectral intensities, infrared band contours, depolarization
      ratios which are supported by normal coordinate calculations. The geometrical
      parameters, harmonic force constants, vibrational frequencies, infrared
      intensities, Raman activities, depolarization ratios, and energy differences have
      been obtained for the anti and gauche conformers from ab initio MP2/6-31G(d)
      calculations. Structural parameters and energy differences have also been
      obtained utilizing the larger 6-311+G(d, p) and 6-311+G(2d, 2p) basis sets. By
      utilizing the previously reported microwave rotational constants for five
      isotopomers of CH(3)SiF(3) along with ab initio predicted structural values, r(0)
      parameters have been obtained for methyltrifluorosilane. Similarly, from the ab
      initio predicted parameters "adjusted r(0)" parameters have been estimated for
      both conformers of n-propyltrifluorosilane. The results are discussed and
      compared with those obtained for some similar molecules.

PMID- 12788469
TI  - DFT studies of the structure and vibrational spectra of 8-hydroxyquinoline N
      oxide.
AB  - The geometry, frequency and intensity of the vibrational bands of 8
      hydroxyquinoline N-oxide (8-HQNO) and its deuterated derivative (8-DQNO) were
      obtained by the density functional theory (DFT) with the BLYP and B3LYP
      functionals and 6-31G(d,p) basis set. The optimized bond lengths and bond angles
      are in good agreement with the X-ray data. The IR and INS spectra of 8-HQNO and 8
      DQNO computed at the DFT level reproduce the vibrational wavenumbers and
      intensities with an accuracy, which allows reliable vibrational assignments.

PMID- 12788471
TI  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by
      silica in inflammation and fibrosis.
AB  - Exposure to particulate silica (most crystalline polymorphs) causes a persistent
      inflammation sustained by the release of oxidants in the alveolar space. Reactive
      oxygen species (ROS), which include hydroxyl radical, superoxide anion, hydrogen
      peroxide, and singlet oxygen, are generated not only at the particle surface, but
      also by phagocytic cells attempting to digest the silica particle. Two distinct
      kinds of surface centers-silica-based surface radicals and poorly coordinated
      iron ions-generate O(2)(*)(-) and HO(*) in aqueous solution via different
      mechanisms. Crystalline silica is also a potent stimulant of the respiratory
      burst in phagocytic cells with increased oxygen consumption and production of
      O(*)(-), H(2)O(2), and NO leading to acute inflammation and HO(*) generation in
      the lung. Oxidative stress elicited by crystalline silica is also evidenced by
      increased expression of antioxidant enzymes such as manganese superoxide
      dismutase (Mn-SOD) and glutathione peroxidase, and the enzyme inducible nitric
      oxide synthase (iNOS). Generation of oxidants by crystalline silica particles and
      by silica-activated cells results in cell and lung injury, activation of cell
      signaling pathways to include MAPK/ERK kinase (MEK), and extracellular signal
      regulated kinase (ERK) phosphorylation, increased expression of inflammatory
      cytokines (e.g., tumor necrosis factoralpha [TNFalpha], interleukin-1 [IL-1]),
      and activation of specific transcription factors (e.g., NFkappaB, AP-1). Silica
      can also initiate apoptosis in response to oxygen- and nitrogen-based free
      radicals, leading to mitochondrial dysfunction, increased gene expression of
      death receptors, and/or their ligands (TNFalpha, Fas ligand [FasL]).

PMID- 12788470
TI  - Molecular packing in sphingomyelin bilayers and sphingomyelin/phospholid
      mixtures.
AB  - The molecular packing properties of sphingomyelin (SM) from egg yolk were
      studied. The influence of the spontaneous curvature of SM on the phase behaviour
      of SM/dodecane/water systems was investigated. A comparison was made to a
      previous study by Lindblom et al. (Liq. Cryst. 3 (1988) 783), of the phase
      behaviour of dipalmitoylphosphatidylcholine (DPPC)/dodecane/water systems, where
      a reversed hexagonal liquid crystalline was shown to form at high water contents
      (60-80%, w/w). In contrast, SM/dodecane/water systems mainly maintained a
      lamellar liquid crystalline phase at all compositions and temperatures >35
      degrees C. This suggests that the spontaneous curvature of SM is larger than for
      DPPC. To further examine the packing properties of SM and DPPC, the phase
      behaviour of SM/dioleoylphosphatidylethanolamine (DOPE)/water and DPPC/DOPE/water
      systems were investigated. Aqueous dispersions of DOPE normally form a reversed
      hexagonal liquid crystalline phase, while an isotropic phase was formed at small
      additions (20 mol.%) of SM or DPPC and a lamellar liquid crystalline phase was
      maintained at higher fractions (>35 mol.%) of SM or DPPC.

PMID- 12788472
TI  - Gene dosage-dependent effects of bcl-2 expression on cellular survival and redox
      status.
AB  - The human oncogene bcl-2 exerts protective functions in numerous models of
      apoptotic cell death and increased oxidative stress. We investigated the effects
      of inducible bcl-2 overexpression on cellular survival and redox status in
      dopaminergic rat pheochromocytoma PC 12 cells. Induction of high-level expression
      of bcl-2 in PC 12 cells resulted in generation of oxidative stress and cessation
      of growth by cell cycle arrest. Cell cycle arrest in bcl-2-overexpressing PC 12
      cells was prevented by an inhibitor of extracellular signal-related kinase (ERK
      1/2) activation. Protective effects of bcl-2 expression against L-DOPA
      neurotoxicity decreased with increasing amounts of bcl-2. Furthermore, high-level
      bcl-2 overexpression sensitized cells towards oxidative stress and glutathione
      depletion. Our data suggest that bcl-2 expression is beneficial only in a limited
      gene dosage range and that high-level expression of bcl-2 exerts potential
      deleterious effects.

PMID- 12788473
TI  - Oxidant-mediated AA release from astrocytes involves cPLA(2) and iPLA(2).
AB  - Excessive generation of reactive oxygen species (ROS) in the central nervous
      system (CNS) is a leading cause of neuronal injury. Despite yet unknown
      mechanisms, oxidant compounds such as H(2)O(2) have been shown to stimulate the
      release of arachidonic acid (AA) in a number of cell systems. In this study,
      H(2)O(2) and menadione, a compound known to release H(2)O(2) intracellularly,
      were used to examine the phospholipases A(2) (PLA(2)) responsible for AA release
      from primary murine astrocytes. Both H(2)O(2) and menadione dose-dependently
      stimulated AA release, and the release mediated by H(2)O(2) was completely
      inhibited by catalase. H(2)O(2) also stimulated phosphorylation of extracellular
      signal-regulated kinases (ERK1/2) and cytosolic phospholipase A(2) (cPLA(2)).
      However, complete inhibition of cPLA(2) phosphorylation by U0126, an inhibitor
      for mitogen-activated protein kinase kinase (MEK) and GF109203x, a nonselective
      PKC inhibitor preferring the conventional and novel isoforms, only reduced
      H(2)O(2)-stimulated AA release by 50%. MAFP, a selective, active, site-directed,
      irreversible inhibitor of both cPLA(2) and the Ca(2+)-independent iPLA(2), nearly
      completely inhibited H(2)O(2)-mediated AA release; but, HELSS, a potent
      irreversible inhibitor of iPLA(2), only inhibited H(2)O(2)-mediated AA release by
      40%. Along with the observation that H(2)O(2)-mediated AA release was only
      partially inhibited upon chelating intracellular Ca(2+) by BAPTA, these results
      indicate the involvement of both cPLA(2) and iPLA(2) in H(2)O(2)-mediated AA
      release in murine astrocytes.

PMID- 12788474
TI  - Enhancing effect of melatonin on chemiluminescence accompanying decomposition of
      hydrogen peroxide in the presence of copper.
AB  - The oxidation of melatonin (MEL) using the Cu(II) + H(2)O(2) + HO(-) (the Fenton
      like reaction) system was investigated by chemiluminescence (CL), fluorescence,
      spectrophotometric, and EPR spin trapping techniques. The reaction exhibits CL in
      the 400-730 nm region. The light emission from the Fenton-like reaction was
      greatly enhanced in the presence of MEL and was strongly dependent on its
      concentration. The spectrum measured with cut-off filters revealed maxima at
      around 460, 500, 580-590, 640-650, and 690-700 nm. The band at 460 nm may be due
      to the excited cleavage product, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine,
      whereas the bands at 500, 580-590, 640-650, and 700 nm were similar to those
      observed for singlet molecular oxygen ((1)O(2)). The effect of reactive oxygen
      species (ROS) scavengers on the light emission was studied. The CL was strongly
      inhibited by the (1)O(2) scavengers in a dose-dependent manner; at concentration
      1 mM the potency of (1)O(2) scavenging was 5,5-dimethylcyclohexandione-1,3 >
      methionine > histidine > hydroquinone. The potency of HO(*) scavenging by
      thiourea, tryptophan, cysteine at concentration 5 mM was 79-94%, by 1 mM
      glutathione and trolox 75 and 94%, respectively, and by 10 mM cimetidine 18%.
      Specific acceptors of O(2)(*)(-) such as p-nitroblue tetrazolium chloride and 4,5
      dihydroxy-1,3-benzene disulfonic acid (tiron) at concentration 5 mM decreased the
      CL by 51 and 95%, respectively, whereas superoxide dismutase (SOD) does not
      reduce the emission at concentration 2.8 U/ml. At higher concentration SOD
      substantially enhanced the light emission. Addition of 1360 U/ml catalase and 100
      microM desferrioxamine strongly inhibited CL (96 and 90%, respectively). The
      increased generation of (1)O(2) from the Cu/H(2)O(2) system in the presence of
      MEL was confirmed using the spectrophotometric method based on the bleaching of p
      nitrosodimethylaniline and by trapping experiments with 2,2,6,6
      tetramethylpiperidine (TEMP) and subsequent electron paramagnetic (EPR)
      spectroscopy. These findings suggest the increased production of reactive oxygen
      species (O(2)(*)(-), HO(*), (1)O(2)) from the Fenton-like reaction in the
      presence of MEL. This means that the hormone is not able to act as classical
      chain-breaking antioxidant even at low concentration, and may show clear
      prooxidant activity at higher concentrations. In addition, long-lived carbonyl
      product of the MEL transformation in the triplet state can also be toxic by
      transferring its energy to organelles and causing a photochemical process.

PMID- 12788475
TI  - Epr analysis reveals three tissues responding to endotoxin by increased formation
      of reactive oxygen and nitrogen species.
AB  - The excessive formation of reactive oxygen and nitrogen species (RONS) in tissue
      has been implicated in the development of various diseases. In this study we
      adopted ex vivo low temperature EPR spectroscopy combined with spin trapping
      technique to measure local RONS levels in frozen tissue samples. CP-H (1-hydroxy
      3-carboxy-pyrrolidine), a new nontoxic spin probe, was used to analyze RONS in
      vivo. In addition, nitrosyl complexes of hemoglobin were determined to trace
      nitric oxide released into blood. By this technique we found that RONS formation
      in tissue of control animals increased in the following order: liver < heart <
      brain < cerebellum < lung < muscle < blood < ileum < kidney < duodenum < jejunum.
      We also found that endotoxin challenge, which represents the most common model of
      septic shock, increased the formation of RONS in rat liver, heart, lung, and
      blood, but decreased RONS formation in jejunum. We did not find changes in RONS
      levels in other parts of gut, brain, skeletal muscles, and kidney. Scavenging of
      RONS by CP-H was accompanied by an increase in blood pressure, indicating that
      LPS-induced vasodilatation may be due to RONS, but not due to nitric oxide.
      Experiments with tissue homogenates incubated in vitro with CP-H showed that
      ONOO(-) and O(2)(*)(-), as well as other not identified RONS, are detectable by
      CP-H in tissue. In summary, low-temperature EPR combined with CP-H infusion
      allowed detection of local RONS formation in tissues. Increased formation of RONS
      in response to endotoxin challenge is organ specific.

PMID- 12788476
TI  - Biomarkers of diabetes-associated oxidative stress and antioxidant status in
      young diabetic patients with or without subclinical complications.
AB  - The aims of the study were to ascertain the potential role of oxidative stress in
      the onset of disease-related pathophysiological complications in young type 1
      diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation,
      and changes in antioxidant defense system status were measured in blood samples
      from 26 young diabetic patients with recently diagnosed (< 6 months)
      microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40
      healthy age-matched controls (CR). Both diabetic groups presented similar
      fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte
      glutathione peroxidase activity, glutathione content, and plasma beta-carotene to
      be significantly lower in diabetic patients compared with control subjects, but
      with no significant differences between -DC and +DC groups. Antioxidant enzyme
      superoxide dismutase activity was significantly higher in the erythrocytes of
      diabetic patients independently of the presence of microvascular complications.
      However, the plasma alpha-tocopherol/total lipids ratio was significantly
      diminished in +DC group compared with -DC (p =.008). Lipid peroxidation indices
      measured in plasma included malondialdehyde, lipid hydroperoxides, and
      lipoperoxides, which were significantly elevated in our diabetic patients
      regardless of the presence of complications. Evidence of oxidative damage to
      proteins was shown both through the quantification of plasma protein carbonyl
      levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and
      higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those
      of controls (0.32 +/- 0.03 mmol/mg prot; p <.01) and immunoblot analysis of
      protein-bound carbonyls. Additionally, a marked increase in protein oxidation was
      observed in +DC patients through assessment of advanced oxidation protein
      products (AOPP) considered to be an oxidized albumin index; AOPP values were
      significantly higher in +DC than in -DC patients (p <.01) and CR (p <.0001).
      These results point to oxidatively modified proteins as a differential factor
      possibly related to the pathogenesis of diabetic complications.

PMID- 12788477
TI  - Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative
      stress in young and elderly men.
AB  - Muscle damage resulting from eccentric exercise provides a useful model of
      oxyradical-induced injury and can be used to examine age-related responses to
      oxidative stress. Sixteen young (26.4 +/- 3.3 years) and 16 older (71.1 +/- 4.0
      years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for
      12 weeks and ran downhill for 45 min at 75% VO(2)max, once before and following
      supplementation. Blood samples were obtained before (baseline) and immediately
      postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant
      status, muscle damage, lipid peroxidation, and DNA damage. Following exercise,
      young and older men experienced similar increases in serum creatine kinase (CK),
      F(2alpha)-isoprostanes (iPF(2alpha); p <.001) and malondialdehyde (MDA; p <.01),
      although iPF(2alpha) peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen
      Radical Absorbance Capacity (ORAC) decreased at 72 h (p <.01) and correlated with
      the rise in iPF(2alpha), MDA, and CK in the young men (p <.05). Leukocyte 8
      hydroxy-2'-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E
      decreased peak CK in young men, while in older men it decreased resting levels of
      iPF(2alpha) and suppressed the 24 h postexercise increases in iPF(2alpha) (p
      <.05). Thus, vitamin E supplementation induced modest changes eccentric exercise
      induced oxidative stress, although differentially between the young and older
      subjects, while age had no direct influence on these responses among this group
      of physically fit subjects.

PMID- 12788478
TI  - Stress-induced activation of GATA-4 in cardiac muscle cells.
AB  - GATA-4 regulates gene transcription in the heart. This study examined whether
      GATA-4 is influenced by stress-induced signaling events. Treatment of HL-1
      cardiac muscle cells with mercury results in the induction of apoptosis that is
      blocked by overexpression of catalase. Similar to daunorubicin (DNR), mercury
      causes downregulation of GATA-4 mRNA expression. However, mercury is less
      effective in inducing apoptosis compared to DNR. Analyses of GATA-4 protein
      expression and activity reveal that mercury initially enhances the GATA-4 DNA
      binding activity, before subsequent downregulation of GATA-4 expression. The
      mercury-induced GATA-4 activation is associated with a phosphorylation of GATA-4,
      which appears to occur via the MEK/ERK pathway. The level of phosphorylated GATA
      4 is more slowly decreased by mercury or actinomycin D, compared to
      unphosphorylated GATA-4, suggesting that phosphorylated GATA-4 is more resistant
      to cellular degradation. Consistent with a previous finding that GATA-4
      phosphorylation induces cell survival, mercury decreases cell death induced by
      DNR. These results suggest that cardiac muscle cells respond to mercury stress by
      eliciting MEK/ERK signaling to form phosphorylated GATA-4 that is more resistant
      to cellular degradation and induce cell survival.

PMID- 12788479
TI  - Mnsod overexpression extends the yeast chronological (G(0)) life span but acts
      independently of Sir2p histone deacetylase to shorten the replicative life span
      of dividing cells.
AB  - Studies in Drosophila and Caenorhabditis elegans have shown increased longevity
      with the increased free radical scavenging that accompanies overexpression of
      oxidant-scavenging enzymes. This study used yeast, another model for aging
      research, to probe the effects of overexpressing the major activity protecting
      against superoxide generated by the mitochondrial respiratory chain. Manganese
      superoxide dismutase (MnSOD) overexpression increased chronological life span
      (optimized survival of stationary (G(0)) yeast over time), showing this is a
      survival ultimately limited by oxidative stress. In contrast, the same
      overexpression dramatically reduced the replicative life span of dividing cells
      (the number of daughter buds produced by each newly born mother cell). This
      reduction in the generational life span by MnSOD overexpression was greater than
      that generated by loss of the major redox-responsive regulator of the yeast
      replicative life span, NAD+-dependent Sir2p histone deacetylase. It was also
      independent of the latter activity. Expression of a mitochondrially targeted
      green fluorescent protein in the MnSOD overexpressor revealed that the old mother
      cells of this overexpressor, which had divided for a few generations, were
      defective in segregation of the mitochondrion from the mother to daughter.
      Mitochondrial defects are, therefore, the probable reason that MnSOD
      overexpression shortens replicative life span.

PMID- 12788480
TI  - Nitric oxide-mediated upregulation of the TGF-beta-inducible early response gene
      1 (TIEG1) in human fibroblasts by mRNA stabilization independent of TGF-beta.
AB  - Nitric oxide serves various roles in mammalian cells, including intracellular
      signaling and cell killing. To recognize the dynamic molecular changes in
      response to NO, microarray analysis was applied to human fibroblasts (IMR-90)
      exposed to sublethal levels of NO. Among the > 300 transcripts induced by NO, we
      focused on the mRNA encoded by the transforming growth factor-beta- (TGF-beta-)
      inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta
      regulated cell growth control and apoptosis. Northern blotting analysis
      demonstrated that NO upregulates TIEG1 mRNA in a dose-dependent manner. Anti-TGF
      beta antibodies prevented TIEG1 mRNA induction by TGF-beta, but not the induction
      by NO. Conversely, NO had no effect on the amounts of total TGF-beta or its
      active form in culture supernatants. However, the half-life of the TIEG1
      transcript was strongly increased (6-fold) upon exposure of the cells to NO.
      Thus, NO upregulates TIEG1 mRNA by stabilization independently of TGF-beta. The
      TIEG1 mRNA now joins heme oxygenase-1 mRNA in displaying regulation by NO
      mediated stabilization. It remains to be determined whether the same control
      mechanism operates on these and perhaps other messages.

PMID- 12788481
TI  - Inhibition of THP-1 cell adhesion to endothelial cells by alpha-tocopherol and
      alpha-tocotrienol is dependent on intracellular concentration of the
      antioxidants.
AB  - Vitamin E analogs such as alpha-tocopherol and alpha-tocotrienol have been shown
      to reduce endothelial expression of adhesion molecules. The reactivity of alpha
      tocopherol and alpha-tocotrienol in inhibiting lipid peroxidation in vitro was
      essentially identical but the inhibition of adhesion of THP-1 cells, a monocytic
      "like" cell line, to endothelial cells differs substantially. To determine the
      mechanism underlying this response, human umbilical vein endothelial cells
      (HUVECs) were assessed for their ability to accumulate vitamin E analogs. alpha
      Tocotrienol accumulated in HUVECs to levels approximately 10-fold greater than
      that of alpha-tocopherol. The decrease in expression of vascular cell adhesion
      molecule-1 (VCAM-1) and the adhesion of THP-1 cells to HUVECs by alpha-tocopherol
      and alpha-tocotrienol was also determined. Both alpha-tocopherol and alpha
      tocotrienol suppressed VCAM-1 expression and adhesion of THP-1 cells to HUVECs in
      a concentration-dependent manner. The efficacy of tocotrienol for reduction of
      VCAM-1 expression and adhesion of THP-1 cells to HUVECs was also 10-fold higher
      than that of tocopherol. The inhibitory effects of vitamin E analogs on the
      adhesiveness of endothelial cells clearly correlated with their intracellular
      concentrations. The data demonstrated that, in assessing the biological responses
      of antioxidants, intracellular accumulation and metabolism were additional
      important factors that must be considered.

PMID- 12788482
TI  - Suppressed apoptosis in the inflamed gastric mucosa of Helicobacter pylori
      colonized iNOS-knockout mice.
AB  - Deregulated cell turnover in Helicobacter pylori (H. pylori)-colonized gastric
      mucosa has been suggested to be linked to the gastric carcinogenesis pathway. We
      previously reported attenuation of apoptosis and enhancement of cellular
      proliferation in the H. pylori-colonized gastric mucosa of Mongolian gerbils as
      compared to that in mice, which might reflect a specific link between H. pylori
      colonization and carcinogenesis in the Mongolian gerbils; the difference between
      the two strains could be attributable to differences in the host genetic
      background. Inducible-type nitric oxide synthase (iNOS) is thought to participate
      in not only the inflammatory response, but also in the regulation of gastric
      mucosal cell turnover in H. pylori-colonized gastric mucosa. Thus, the present
      study was designed to examine gastric leukocyte activation and epithelial cell
      apoptosis in the gastric mucosa following H. pylori inoculation in iNOS-knockout
      mice. METHODS: iNOS-knockout mice (iNOS(-/-)) and their iNOS(+/+) littermates
      were orally inoculated with the Sydney strain of H. pylori (SS1, 10(8) colony
      forming units [CFU]). H. pylori infection was confirmed by microaerobic bacterial
      culture. The stomach of each mouse was evaluated 14 weeks and 30 weeks after the
      inoculation. Gastric mucosal accumulation of polymorphonuclear leukocytes (PMN)
      was assessed by determining the myeloperoxidase (MPO) activity and histological
      score based on the updated Sydney system. The level of apoptosis was determined
      by estimation of the cytoplasmic levels of mono- and oligonucleosomes and by the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling method. RESULTS: The SS1-inoculated mice showed persistent H. pylori
      colonization for 12 weeks. While gastric mucosal PMN infiltration increased
      following SS1 inoculation in both iNOS(+/+) and iNOS(-/-)strains, enhanced DNA
      fragmentation was observed in only SS1-colonized iNOS(+/+) mice, and not in the
      iNOS(-/-) mice. In conclusion, although the recruitment of PMN in response to H.
      pylori was evoked even in the gastric mucosa of iNOS(-/-) mice, epithelial cell
      apoptosis induced by H. pylori was attenuated in this strain. These data suggest
      that iNOS may play an important role in promoting apoptosis in the H. pylori
      infected inflamed gastric mucosa, and that persistent inflammation without
      apoptosis in iNOS(-/-) mice with H. pylori infection may be linked to
      preneoplastic transformation.

PMID- 12788483
TI  - Age-independent, gray matter-localized, brain-enhanced oxidative stress in male
      fischer 344 rats: brain levels of F(2)-isoprostanes and F(4)-neuroprostanes.
AB  - While studies showed that aging is accompanied by increased exposure of the brain
      to oxidative stress, others have not detected any age-correlated differences in
      levels of markers of oxidative stress. Use of conventional markers of oxidative
      damage in vivo, which may be formed ex vivo and/or eliminated by endogenous
      metabolism, may explain these conflicting results. Recently, F(2)-isoprostanes
      and F(4)-neuroprostanes, peroxidation products of arachidonic acid and
      docosahexaenoic acid, respectively, have been identified as sensitive and
      reliable markers of oxidative injury. Therefore, this study was designed to
      quantify brain levels of F(2)-isoprostanes and F(4)-neuroprostanes and their
      precursors in 4, 10, 50, and 100 week old male Fischer 344 rats. Data show that
      levels of F(2)-isoprostanes and F(4)-neuroprostanes were comparable in all animal
      age groups. However, levels of F(4)-neuroprostanes were approximately 20-fold
      higher than those of F(2)-isoprostanes in all age groups, despite the fact that
      brain levels of docosahexaenoic acid were only twice as high as those of
      arachidonic acid. Based on our findings, it is concluded that aging is not
      accompanied by enhanced brain susceptibility to oxidative stress. Furthermore,
      the metabolically active gray matter of the brain, where docosahexaenoic acid is
      abundant, appears more susceptible to oxidative stress than the white matter.

PMID- 12788485
TI  - Structural insights into the mechanism of proton pumping by bacteriorhodopsin.
AB  - For over three decades, bacteriorhodopsin has served as a paradigm for the study
      of the mechanisms underlying ion pumping across biological membranes. It is
      perhaps among the simplest known ion pumps, which functions by converting light
      energy into an electrochemical gradient by pumping protons out of the cytoplasm.
      The combination of spectroscopic, biochemical and crystallographic studies on
      bacteriorhodopsin provides a unique opportunity to dissect the principal elements
      underlying the mechanism of transmembrane proton transport. Here, we provide a
      brief review of recent developments related to the determination of the
      structural changes during proton transport using crystallographic approaches.
      Taken together with previous spectroscopic and biochemical investigations, these
      studies allow the description of a detailed molecular mechanism of the main steps
      in vectorial proton transport by bacteriorhodopsin.

PMID- 12788486
TI  - Proton pumping by NADH:ubiquinone oxidoreductase. A redox driven conformational
      change mechanism?
AB  - The modular evolutionary origin of NADH:ubiquinone oxidoreductase (complex I)
      provides useful insights into its functional organization. Iron-sulfur cluster N2
      and the PSST and 49 kDa subunits were identified as key players in ubiquinone
      reduction and proton pumping. Structural studies indicate that this 'catalytic
      core' region of complex I is clearly separated from the membrane. Complex I from
      Escherichia coli and Klebsiella pneumoniae was shown to pump sodium ions rather
      than protons. These new insights into structure and function of complex I
      strongly suggest that proton or sodium pumping in complex I is achieved by
      conformational energy transfer rather than by a directly linked redox pump.

PMID- 12788487
TI  - Proton translocation by transhydrogenase.
AB  - Transhydrogenase, in animal mitochondria and bacteria, couples hydride transfer
      between NADH and NADP(+) to proton translocation across a membrane. Within the
      protein, the redox reaction occurs at some distance from the proton translocation
      pathway and coupling is achieved through conformational changes. In an 'open'
      conformation of transhydrogenase, in which substrate nucleotides bind and product
      nucleotides dissociate, the dihydronicotinamide and nicotinamide rings are held
      apart to block hydride transfer; in an 'occluded' conformation, they are moved
      into apposition to permit the redox chemistry. In the two monomers of
      transhydrogenase, there is a reciprocating, out-of-phase alternation of these
      conformations during turnover.

PMID- 12788488
TI  - Protonmotive force generation by a redox loop mechanism.
AB  - Respiration involves the oxidation and reduction of substrate for the redox
      linked formation of a protonmotive force (PMF) across the inner membrane of
      mitochondria or the plasma membrane of bacteria. A mechanism for PMF generation
      was first suggested by Mitchell in his chemiosmotic theory. In the original
      formulations of the theory, Mitchell envisaged that proton translocation was
      driven by a 'redox loop' between two catalytically distinct enzyme complexes.
      Experimental data have shown that this redox loop does not operate in
      mitochondria, but has been confirmed as an important mechanism in bacteria. The
      nitrate respiratory pathway in Escherichia coli is a paradigm for a protonmotive
      redox loop. The structure of one of the enzymes in this two-component system,
      formate dehydrogenase-N, has revealed the structural basis for the PMF generation
      by the redox loop mechanism and this forms the basis of this review.

PMID- 12788489
TI  - Variation in proton donor/acceptor pathways in succinate:quinone oxidoreductases.
AB  - The anaerobically expressed fumarate reductase and aerobically expressed
      succinate dehydrogenase from Escherichia coli comprise two different classes of
      succinate:quinone oxidoreductases (SQR), often termed respiratory complex II. The
      X-ray structures of both membrane-bound complexes have revealed that while the
      catalytic/soluble domains are structurally similar the quinone binding domains of
      the enzyme complexes are significantly different. These results suggest that the
      anaerobic and aerobic forms of complex II have evolved different mechanisms for
      electron and proton transfer in their respective membrane domains.

PMID- 12788490
TI  - Protonmotive pathways and mechanisms in the cytochrome bc1 complex.
AB  - The cytochrome bc(1) complex catalyzes electron transfer from ubiquinol to
      cytochrome c by a protonmotive Q cycle mechanism in which electron transfer is
      linked to proton translocation across the inner mitochondrial membrane. In the Q
      cycle mechanism proton translocation is the net result of topographically
      segregated reduction of quinone and reoxidation of quinol on opposite sides of
      the membrane, with protons being carried across the membrane as hydrogens on the
      quinol. The linkage of proton chemistry to electron transfer during quinol
      oxidation and quinone reduction requires pathways for moving protons to and from
      the aqueous phase and the hydrophobic environment in which the quinol and quinone
      redox reactions occur. Crystal structures of the mitochondrial cytochrome bc(1)
      complexes in various conformations allow insight into possible proton conduction
      pathways. In this review we discuss pathways for proton conduction linked to
      ubiquinone redox reactions with particular reference to recently determined
      structures of the yeast bc(1) complex.

PMID- 12788492
TI  - The role of electrostatics in proton-conducting membrane protein complexes.
AB  - Electrostatic interactions play a key role in the coupling of electron and proton
      transfer in membrane protein complexes during the conversion of the energy stored
      in sunlight or reduced substrates into biochemical energy via a transmembrane
      electrochemical proton potential. Principles of charge stabilization within
      membrane proteins are reviewed and discussed for photosynthetic reaction centers,
      cytochrome c oxidases, and diheme-containing quinol:fumarate reductases. The
      impact of X-ray structure-based electrostatic calculations on the functional
      interpretation of these structural coordinates, on providing new explanations for
      experimental observations, and for the design of more focused additional
      experiments is illustrated by a number of key examples.

PMID- 12788491
TI  - Understanding the mechanism of proton movement linked to oxygen reduction in
      cytochrome c oxidase: lessons from other proteins.
AB  - Cytochrome c oxidase is a large intrinsic membrane protein designed to use the
      energy of electron transfer and oxygen reduction to pump protons across a
      membrane. The molecular mechanism of the energy conversion process is not
      understood. Other proteins with simpler, better resolved structures have been
      more completely defined and offer insight into possible mechanisms of proton
      transfer in cytochrome c oxidase. Important concepts that are illustrated by
      these model systems include the ideas of conformational change both close to and
      at a distance from the triggering event, and the formation of a transitory water
      linked proton pathway during a catalytic cycle. Evidence for the applicability of
      these concepts to cytochrome c oxidase is discussed.

PMID- 12788493
TI  - ATP synthesis driven by proton transport in F1F0-ATP synthase.
AB  - Topical questions in ATP synthase research are: (1) how do protons cause subunit
      rotation and how does rotation generate ATP synthesis from ADP+Pi? (2) How does
      hydrolysis of ATP generate subunit rotation and how does rotation bring about
      uphill transport of protons? The finding that ATP synthase is not just an enzyme
      but rather a unique nanomotor is attracting a diverse group of researchers keen
      to find answers. Here we review the most recent work on rapidly developing areas
      within the field and present proposals for enzymatic and mechanoenzymatic
      mechanisms.

PMID- 12788494
TI  - Molecular evolution of the modulator of chloroplast ATP synthase: origin of the
      conformational change dependent regulation.
AB  - Chloroplast ATP synthase synthesizes ATP by utilizing a proton gradient as an
      energy supply, which is generated by photosynthetic electron transport. The
      activity of the chloroplast ATP synthase is regulated in several specific ways to
      avoid futile hydrolysis of ATP under various physiological conditions. Several
      regulatory signals such as Delta mu H(+), tight binding of ADP and its release,
      thiol modulation, and inhibition by the intrinsic inhibitory subunit epsilon are
      sensed by this complex. In this review, we describe the function of two
      regulatory subunits, gamma and epsilon, of ATP synthase based on their possible
      conformational changes and discuss the evolutionary origin of these regulation
      systems.

PMID- 12788495
TI  - Proton translocation driven by ATP hydrolysis in V-ATPases.
AB  - The vacuolar H(+)-ATPases (or V-ATPases) are a family of ATP-dependent proton
      pumps responsible for acidification of intracellular compartments and, in certain
      cases, proton transport across the plasma membrane of eukaryotic cells. They are
      multisubunit complexes composed of a peripheral domain (V(1)) responsible for ATP
      hydrolysis and an integral domain (V(0)) responsible for proton translocation.
      Based upon their structural similarity to the F(1)F(0) ATP synthases, the V
      ATPases are thought to operate by a rotary mechanism in which ATP hydrolysis in
      V(1) drives rotation of a ring of proteolipid subunits in V(0). This review is
      focused on the current structural knowledge of the V-ATPases as it relates to the
      mechanism of ATP-driven proton translocation.

PMID- 12788496
TI  - Flagellar movement driven by proton translocation.
AB  - The bacterial flagellar motor couples ion flow to rotary motion at high speed and
      with apparently fixed stoichiometry. The functional properties of the motor are
      quite well understood, but its molecular mechanism remains unknown. Recent
      studies of motor physiology, coupled with mutational and biochemical studies of
      the components, put significant constraints on the mechanism. Rotation is
      probably driven by conformational changes in membrane-protein complexes that form
      the stator. These conformational changes occur as protons move on and off a
      critical Asp residue in the stator protein MotB, and the resulting forces are
      applied to the rotor protein FliG.

PMID- 12788498
TI  - Distinct forelimb and hind limb stepping impairments in unilateral dopamine
      depleted rats: use of the rotorod as a method for the qualitative analysis of
      skilled walking.
AB  - The rotorod test, in which animals walk on a rotating drum, is widely used to
      assess motor status in laboratory rodents. Performance is measured by the
      duration that an animal stays up on the drum as a function of drum speed. Here we
      report that the task provides a rich source of information about qualitative
      aspects of walking movements. Because movements are performed in a fixed
      location, they can readily be examined using high-speed video recording methods.
      The present study was undertaken to examine the potential of the rotorod to
      reveal qualitative changes in the walking movements of hemi-Parkinson analogue
      rats, produced by injection of 6-hydroxydopamine (6-OHDA) into the nigrostriatal
      bundle to deplete nigrostriatal dopamine (DA). Beginning on the day following
      surgery and then periodically over the next two months, the rats were filmed from
      frontal, lateral, and posterior views as they walked on the rotorod. Behavior was
      analyzed by frame-by-frame replay of the video records. Rating scales of stepping
      behavior indicated that the hemi-Parkinson rats were chronically impaired in
      their posture and in the use of the limbs contralateral to the DA-depletion. The
      contralateral limbs not only displayed postural and movement abnormalities, they
      participated less in initiating and sustaining propulsion than did the
      ipsilateral limbs. These findings not only reveal new deficits secondary to
      unilateral DA-depletion, but also show that the rotorod can provide a robust tool
      for the qualitative analysis of movement.

PMID- 12788497
TI  - Characterization of probe and tissue factors that influence interpretation of
      quantitative microdialysis experiments for dopamine.
AB  - Two quantitative methods, the Lonnroth (no-net-flux) and variation of perfusion
      flow rate methods, were used to investigate the influence of the probe and tissue
      on dopamine microdialysis measurements. In vivo measurements were made in the
      nucleus accumbens of awake, freely moving rats on two consecutive days of
      dialysis. The results of the no-net-flux study showed that there was no
      statistically significant difference in extraction fraction at a perfusion flow
      rate of 2.0 microl/min between in vitro in a well-stirred solution and in vivo
      measured during 2 days of continuous dialysis. Also, varying the perfusate flow
      rate over the range 0.25-2.0 microl/min produced a variation in the extraction
      fraction that was the same in vitro and in vivo. These results indicate that the
      extraction fraction for dopamine over the 2 days was dominated by the properties
      of the probe. The negligible influence of the tissue on dopamine extraction
      fraction was probably due to the high basal activity of the dopamine transporter
      in vivo. Therefore, the extraction fraction is unlikely to be sensitive to
      increases in dopamine uptake in the vicinity of the probe. The apparent
      extracellular dopamine concentration increased by 37% on the second day of
      dialysis while the calcium-dependence of basal dialysate dopamine levels declined
      by 20%. These findings are consistent with a decrease in physiological viability
      of the dopamine nerve terminals surrounding the probe during a long-term
      experiment.

PMID- 12788500
TI  - Open space swimming test to index antidepressant activity.
AB  - Depression is characterized by a lack of "motivation" rather than a lack of
      "physical space" to move around. This study was designed to evaluate predictivity
      of an open space swimming test for antidepressant activity of various
      antidepressants in rats. Without drug treatment, rats showed a significant
      reduction in the distance moved (increased immobility) over successive trials in
      an open space water pool. Three major classes of antidepressants and a selective
      serotonin reuptake inhibitor (SSRI) were tested. Repeated treatment (10 mg/kg x 3
      per day) of imipramine, a prototypical tricyclic antidepressant, iproniazid, a
      monoamine oxidase inhibitor, mianserin, an atypical antidepressant, and
      alaproclate, an SSRI, all significantly reduced the immobility. These results
      suggest that the open space swimming test is highly predictive of antidepressant
      action and is more sensitive to the drug treatments. The measurement is more
      objective than that of the forced swimming test and does not involve judging and
      scoring the animals' movement or lack of movement by investigators. The
      demonstrated effectiveness of three major types of antidepressants and an SSRI
      suggests that the effects on the test are not restricted to a particular
      underlying molecular mechanism of action. Thus, this swimming test shows
      promising potential as a screen for novel antidepressants and, perhaps, for
      revealing some of the underlying pathophysiology of depression.

PMID- 12788499
TI  - Immunohistochemical detection of wheat germ agglutinin-horseradish peroxidase
      (WGA-HRP).
AB  - Traditional histochemical detection of wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) can impose substantial technical limitations on studies
      requiring co-localization of neurotransmitters, receptors and other neural
      antigens. The goal of our experiments was to establish the ideal conditions and
      reagents for immunohistochemical detection of WGA-HRP. WGA-HRP was injected into
      the tongues and vibrissae pads of adult rats to characterize labeling of somas
      and synapses, respectively. Rats were perfused with either 4% paraformaldehyde
      (for light microscopy, LM) or 4% paraformaldehyde/0.15% glutaraldehyde (for
      electron microscopy, EM) after survival times of 2, 3, 4, 5 or 6 days. For LM,
      brainstem tissue was cut on a cryostat at 20 microm and collected onto glass
      slides. For EM, tissue was sectioned with a vibratome at 50 microm and processed
      free floating. For LM, WGA-HRP was detected with goat anti-HRP, goat anti-WGA,
      biotinylated goat anti-HRP or biotinylated goat anti-WGA antibodies. For EM, WGA
      HRP was detected with biotinylated goat anti-WGA and anti-HRP antibodies.
      Survival intervals of 3 days were ideal for staining of hypoglossal neurons,
      whereas an interval of 4 days produced the strongest staining of synapses within
      the spinal trigeminal nucleus. For LM, the biotinylated antibodies resulted in
      better signal-to-noise ratios than the unconjugated antibodies. At both the LM
      and EM levels, the biotinylated antibody to WGA produced better quality staining
      than the biotinylated antibody to HRP.

PMID- 12788501
TI  - Simultaneous mapping of binocular and monocular receptive fields in awake monkeys
      for calibrating eye alignment in a dichoptical setup.
AB  - We developed a modified Wheatstone stereoscope for simultaneous dichoptical and
      binocular stimulation in awake monkey. We, therefore, extended the conventional
      two-screen Wheatstone stereoscope to a setup with an additional third screen
      viewed binocularly via semi-transparent mirrors. With a sparse noise stimulation
      we mapped classical receptive field (CRF) positions via each screen independently
      but simultaneously. This was done for multiple recording positions (16
      electrodes) at once in primary visual cortex based on multiple unit spike
      activity (MUA) and local field potentials (LFP), respectively. The technique can
      be used to (1) quickly and simultaneously determine binocular as well as left and
      right eye CRFs, including ocular dominance characteristics (net recording time
      for the given examples: approximately 2 min), (2) precisely adjust dichoptical
      stimulation by evaluating offsets between monocular and binocular CRF positions
      (average spatial incongruency between binocular and left/right eye stimulation
      after calibration: approximately 0.025 degrees visual angle), and (3) investigate
      left and right eye interaction in forming binocular CRFs. Due to the precise
      adjustment of the dichoptical and the simultaneous binocular stimulation
      investigations on the basis of stereo vision can be done with appropriate eye
      vergence alignment matching normal binocular viewing conditions in awake animals.

PMID- 12788502
TI  - [3H]Dopamine release in striatum in response to cortical stimulation in a
      corticostriatal slice preparation.
AB  - A new method has been developed to investigate corticostriatal glutamatergic
      influence on [3H]dopamine release in striatum in complex corticostriatal slice
      preparation in vitro. Horizontal slices containing the striatum and the adjacent
      prefrontal cortex of rat brain were cut in a plane that maintains corticostriatal
      connections. After incubation with [3H]dopamine, slices were submerged in a two
      compartment bath so that the cortical region was contained entirely in one
      compartment, corpus callosum passed through a silicone greased slot, and the
      striatal region was contained in the other compartment. A cannula was placed just
      above the striatal part of the slice and effluent was collected with a
      peristaltic pump, released tritiated materials were counted with a liquid
      scintillation counter. Electric field stimulation of cortex increased the release
      of [3H]dopamine in the striatum. Bicuculline (1 mM) increased the basal and
      stimulated release of [3H]dopamine in the striatum in response to cortical
      stimulation of cortex indicating the GABAergic control on dopamine release. This
      method allows investigation of the effect of cortical stimulation on glutamate
      dopamine-GABA interactions in the striatum in vitro that might help to understand
      better the neurochemical background of schizophrenia or Parkinson's disease.

PMID- 12788503
TI  - Identification of human cells in brain xenografts and in neural co-cultures of
      rat by in situ hybridisation with Alu probe.
AB  - Transplantation of human cells into animal models of neurodegenerative disorders
      is an important scientific application to analyse the survival and developmental
      capacity of grafted human cells under in vivo conditions. It is critical,
      therefore, to have a reliable method to distinguish between human and animal
      cells. In the present study, we describe a combined in situ hybridisation and
      immunocytochemistry method for the identification of human cells in cultured rat
      brain cells and xenografts. The specific Alu probe we utilised, which corresponds
      to the consensus sequence of human Alu repeats was evaluated by southern blot
      hybridisation of zoo blot and by in situ hybridisation of primary and neoplastic
      cells from man, rat, mouse, and hamster. This method allows a definite
      identification of human cells in neural xenografts and, in combination with
      additional in situ techniques, a further detection of grafted cells.

PMID- 12788504
TI  - Evaluation of methods for eliciting somatosensory-evoked potentials in the awake,
      freely moving rat.
AB  - To standardise the method of eliciting somatosensory-evoked potentials (SEPs),
      SEPs were generated by electrical stimulation of different stimulus sites and
      recorded bilaterally from the primary somatosensory cortex (S1) and from midline
      in awake, freely moving rats. Increasing stimulus intensity enhanced amplitudes
      of all SEPs. At supramaximal stimulation, SEPs following vibrissae and tail
      stimulation (V-SEP and Ta-SEP, respectively) but not following trunk stimulation
      (Tr-SEP), fulfilled our criterion of signal-to-noise ratio >or=4. The first V-SEP
      component coincided with a stimulus artefact, disqualifying these recordings for
      a standard stimulation protocol. The Ta-SEP generated stable and reproducible
      recordings and was considered to be the preferred technique. Early components of
      the contralateral S1 recorded V-SEP and Tr-SEP occurred at latencies different
      from the other recordings. Increasing stimulus repetition rate (SRR) decreased
      amplitudes of all SEPs. At the highest obtainable SRR, the amplitude between the
      V-SEP second positive and second negative components in all recordings was 70-80%
      of the amplitude at 0.1 Hz, whereas peak amplitudes of subsequent components and
      those of the Tr-SEP and Ta-SEP were 20-50%. These results indicate that the
      different SEP components might be generated by different ascending neural
      pathways.

PMID- 12788505
TI  - High-efficiency transfection of individual neurons using modified
      electrophysiology techniques.
AB  - Transfection of cells by electroporation is a widely used and efficient method.
      Recently, it has been shown that single neurons in brain slice cultures can be
      transfected using micropipettes loaded with plasmid DNA expression constructs.
      However, the transfection efficiencies were very low. Routine employment of
      single-cell electroporation (SCE) for transfection of neurons requires high and
      reliable efficiency together with good cell survival. Here, we describe the
      modification of electrophysiology techniques for SCE leading to very simple and
      efficient (up to 80%) transfection of neurons in organotypic rat hippocampus and
      mouse cortex slice cultures. Electroporation-mediated transfection was visualized
      in real-time by two-photon microscopy at the cellular level using fluorescently
      labeled oligonucleotides and plasmid DNA. Small oligonucleotides enter the cell
      immediately during pulse application while large plasmids remain localized for
      more than 10 min at the cell membrane before they enter the cell by an, as yet,
      unknown process. SCE does not affect the electrophysiology of transgene
      expressing cells. Expression of several neuronal green fluorescent protein-tagged
      proteins demonstrates that the method can be employed to analyze subcellular
      trafficking and targeting in single living neurons.

PMID- 12788506
TI  - A model experimental system for monitoring changes in sensory neuron phenotype
      evoked by tooth injury.
AB  - The dental pulp is a favorable model for studies of interactions between
      nociceptive sensory neurons and their peripheral target tissues. In the present
      study, we retrogradely labeled pulpal afferent neurons with an improved method
      that permits monitoring of changes in neuronal phenotype in response to
      controlled tooth injuries. The capacity of retrograde neuronal tracers to diffuse
      through dentinal tubules was exploited, thereby avoiding the severe injury to the
      pulp associated with previous tracer application methods. The strategy was to
      apply the durable fluorescent tracer, Fluoro-gold (FG), to exposed dentin in the
      floor of shallow cavities in molars, in order to pre-label pulpal neurons in
      trigeminal ganglia of young adult Sprague-Dawley rats. A high percentage of pupal
      afferent neurons were retrogradely labeled by application of FG to exposed dentin
      and the FG fluorescent signal persisted in most labeled neurons for at least 8
      weeks. Following tracer application to dentin, the pulp tissue appeared normal
      histologically, with the exception that a layer of reactive dentin was deposited
      at the pulp-dentin border beneath the shallow cavities. Assessment of expression
      of calcitonin gene-related peptide (CGRP) and brain derived neurotrophic factor
      (BDNF) indicated that pulpal neurons remained in a quiescent, baseline condition
      cytochemically following application of tracer to cavities in dentin and
      upregulation of these markers could be detected in neurons that projected to
      teeth that received a test injury subsequent to tracer application. Thus,
      labeling of trigeminal neurons via dentinal tubules provides the basis for a
      useful model for precisely assessing properties of pulpal afferents in both
      quiescent and activated states.

PMID- 12788507
TI  - Antigenic compartmentation of the cat cerebellar cortex.
AB  - Despite the apparent uniformity in cellular composition of the mammalian
      cerebellar cortex, a complex topography is revealed by several expression
      patterns. Zebrin II, a polypeptide antigen identified as aldolase C, is one such
      marker which, in several species of mammals, is restricted to a subset of
      Purkinje cells that are clustered together to form a symmetrical and reproducible
      array of zones and stripes. In rodents the cerebellar cortex is divided into four
      transverse zones--anterior, central, posterior, and nodular. Each transverse zone
      is further subdivided mediolaterally into an array of parasagittal stripes. The
      similar zone and stripe organization partitions the hemispheres. Based upon a
      novel whole mount immunohistochemical staining procedure, we have now identified
      homologous zones and stripes in the feline cerebellum. In the cat cerebellum the
      somata of most Purkinje cells express zebrin II but parasagittal stripes may
      still be delineated owing to the alternating high and low zebrin II expression
      levels in the dendritic arbors. As in rodents, the cat cerebellum consists of
      four transverse zones with each zone subdivided into a unique combination of
      zebrin II parasagittal stripes, suggesting that a common architecture underlies
      the organization of the mammalian cerebellum.

PMID- 12788508
TI  - Degeneration of beta-amyloid-associated cholinergic structures in transgenic APP
      SW mice.
AB  - Cholinergic dysfunction is a consistent feature of Alzheimer's disease, and the
      interrelationship between beta-amyloid deposits, inflammation and early
      cholinergic cell loss is still not fully understood. To characterize the
      mechanisms by which beta-amyloid and pro-inflammatory cytokines may exert
      specific degenerating actions on cholinergic cells ultrastructural investigations
      by electron microscopy were performed in brain sections from transgenic Tg2576
      mice that express the Swedish double mutation of the human amyloid precursor
      protein and progressively develop beta-amyloid plaques during aging. Both light
      and electron microscopical investigations of the cerebral cortex of 19-month-old
      transgenic mice revealed a number of pathological tissue responses in close
      proximity of beta-amyloid plaques, such as activated microglia, astroglial
      proliferation, increased number of fibrous astrocytes, brain edema, degeneration
      of nerve cells, dendrites and axon terminals. Ultrastructural detection of
      choline acetyl transferase (ChAT)-immunostaining in cerebral cortical sections of
      transgenic mice clearly demonstrated degeneration of ChAT-immunoreactive fibres
      in the environment of beta-amyloid plaques and activated glial cells suggesting a
      role of beta-amyloid and/or inflammation in specific degeneration of cholinergic
      synaptic structures.

PMID- 12788509
TI  - Insulin affects synaptosomal GABA and glutamate transport under oxidative stress
      conditions.
AB  - In this study, we investigated the in vitro effect of exogenously administered
      insulin on the susceptibility to oxidative stress and on the accumulation of the
      amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in a
      synaptosomal fraction isolated from male Wistar rat brain cortex. Insulin (1
      microM) did not affect synaptosomal lipid peroxidation induced by the oxidant
      pair ascorbate/Fe(2+), although under these conditions an increase in
      thiobarbituric acid reactive substances (TBARS) levels was observed. Under
      control conditions, the presence of insulin did not change the uptake of [3H]GABA
      or [3H]glutamate. In contrast, under oxidizing conditions, we observed a 1.8- and
      a 2.2-fold decrease in [3H]GABA and [3H]glutamate accumulation, respectively, and
      insulin reverted the lower levels of both [3H]GABA and [3H]glutamate accumulation
      (to 86.74+/-6.26 and 67.01+/-6.65% of control, respectively). Insulin also
      increased the extrasynaptosomal levels of GABA and glutamate, determined both in
      control and oxidizing conditions. From this study, we can conclude that insulin
      is a modulator of amino acid neurotransmitter transport, either directly, as
      seems to occur under normal conditions, or via the decrease in ATP levels and the
      subsequent reversion of the amino acid transporters, as seems to occur under
      oxidative stress conditions. The modulation of both GABA and glutamate transport
      might be implicated in the neuroprotective role of insulin.

PMID- 12788510
TI  - Deficits in avoidance responding after paradoxical sleep deprivation are not
      associated with altered [3H]pirenzepine binding to M1 muscarinic receptors in rat
      brain.
AB  - Previous work had indicated that animals that were sleep-deprived and then
      trained on a passive avoidance task show poor retention of the task 24 h later
      after being allowed to sleep freely again. Cholinergic involvement is suggested
      by the fact that this effect is prevented by treatment with the muscarinic
      agonist pilocarpine during sleep deprivation. The observation that similar
      deficits are observed in non-deprived rats after treatment with M1-selective
      antagonist compounds such as dicyclomine or pirenzepine cause similar
      impairments, and gave rise to the hypothesis that sleep deprivation might induce
      significant reductions in M1 binding in brain areas involved in learning and
      memory processes. Rats were deprived of sleep for 96 h and then either
      immediately killed, or allowed to recover sleep for 24 h before being killed.
      [3H]pirenzepine binding to M1 sites was examined by quantitative autoradiography
      in 39 different brain areas in cage controls, sleep-deprived and sleep-recovered
      animals (N=8 per group). No significant differences among groups were found in
      any brain region. A separate group of animals was subjected to the sleep
      deprivation procedure and then trained in a simple avoidance task. Animals were
      then allowed to sleep and retested 24 h later. This group showed a significant
      impairment in the avoidance task compared to cage controls, in agreement with
      previous observations. These data suggest that proactive learning/memory deficits
      induced by sleep deprivation cannot be attributed to altered M1 binding either
      immediately after deprivation (when avoidance training occurs) or after sleep has
      recovered (when acquisition/retention are tested). The possibility remains that
      alterations in M1 function occur at post-membrane second messenger systems.

PMID- 12788511
TI  - Transgenic mice expressing the betaAPP695SWE mutation: effects on exploratory
      activity, anxiety, and motor coordination.
AB  - The functional consequences of the betaAPP transgene with the Swedish mutation in
      mice were assessed in tests of exploratory activity and motor coordination. The
      betaAPP(695)SWE (Tg2576) transgenic mice are characterized by Abeta plaque
      formation in the neocortex and hippocampus. By comparison to non-transgenic mice
      controlled for age and gender, 17-month-old betaAPP(695)SWE transgenic mice
      displayed impaired spontaneous alternation, increased activity levels in the
      peripheral part of the open-field, and reduced anxiety in the elevated plus-maze.
      These results are similar to the loss of inhibitory control observed in some
      patients with Alzheimer's disease. These measures may be added to cognitive
      dysfunctions as testing ground for Abeta vaccination and other attempts at
      experimental therapies.

PMID- 12788512
TI  - Neuroprotective effect of nitric oxide against NMDA-induced neurotoxicity in the
      rat retina is associated with tyrosine hydroxylase expression.
AB  - N-methyl-D-aspartate (NMDA) may affect dopaminergic cells, which contain tyrosine
      hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. To clarify the
      involvement of TH in the neuroprotective effects of nitric oxide (NO), we
      investigated whether NMDA alters TH mRNA and TH protein levels and whether NO
      inhibits NMDA-induced changes in the rat retina. Dopamine levels in the retina
      were measured by high-performance liquid chromatography (HPLC). Reverse
      transcription-polymerase chain reaction (RT-PCR) and real-time PCR showed that
      intravitreal injection of NMDA caused a significant reduction in TH mRNA levels
      in the retina. Similarly, Western blot analysis showed that NMDA decreased the
      production of TH protein. These reductions in TH mRNA and TH protein levels were
      attenuated by concomitant injection of NOC 18, an NO donor. HPLC analysis showed
      that NMDA reduced dopamine levels in the retina and that NO attenuated this
      reduction. Furthermore, morphological analysis showed that NO prevents NMDA
      induced neurotoxicity through dopamine D(1) receptors. These results suggest that
      the neuroprotective effect of NO may be associated with the induction of TH
      expression and increased levels of dopamine.

PMID- 12788513
TI  - Effects of head-down tilt on the intracranial pressure in conscious rabbits.
AB  - Head-down tilt (HDT) causes a fluid shift towards the upper body, which increases
      intracranial pressure (ICP). In the present study, the time course of ICP changes
      during prolonged exposure to HDT was investigated in conscious rabbits through a
      catheter chronically implanted into the subarachnoid space. The production of
      cerebrospinal fluid (CSF) after exposure to 7-days HDT was also examined by a
      ventriculo-cisternal perfusion method. The ICP increased from 4.3+/-0.4 (mean+/
      S.E.M.) mmHg to 8.0+/-0.8 mmHg immediately after the onset of 45 degrees HDT,
      reached a peak value of 15.8+/-1.9 mmHg at 11 h, and then decreased to 10.4+/-1.1
      mmHg at 24 h. During 7-days HDT, it also increased from 4.8+/-0.9 mmHg to 9.2+/
      1.6 mmHg immediately after the onset of 45 degrees HDT, reached a peak value of
      12.8+/-2.5 mmHg at 12 h of HDT, and then decreased gradually towards the pre-HDT
      baseline value for 7 days. The rate of CSF production was 10.1+/-0.6 microl/min
      in rabbits exposed to 7-days HDT, and 9.7+/-0.5 microl/min in control rabbits.
      These results suggest that the rabbits begin to adapt to HDT within a few days
      and that the production of CSF is preserved after exposure to 7-days HDT. The
      time course of ICP changes during HDT in conscious rabbits seems to be
      considerably different from that in anesthetized rabbits.

PMID- 12788514
TI  - Transient forebrain ischemia modulates signal transduction from extracellular
      matrix in gerbil hippocampus.
AB  - Cell adhesion to the extracellular matrix (ECM) functions as a survival factor
      and disruption of cell-ECM interaction can lead to cell death. Our previous study
      has demonstrated ischemia-induced enhancement of activity of extracellular
      metalloproteinases, which might result in the alteration of adhesive contact with
      ECM and affect the intracellular signaling pathway. The enzyme thought to play a
      major role in conveying survival signals from ECM to the cell interior is focal
      adhesion kinase (pp125(FAK)). In the present study, the temporal relation between
      activation of extracellular metalloproteinases (MMP-2 and MMP-9), degradation of
      extracellular matrix protein laminin and the expression of pp125(FAK) after 5 min
      of global ischemia in gerbil hippocampus were investigated. While significant
      activation of both investigated metalloproteinases occurred in the course of
      reperfusion, only changes in MMP-9 activity were correlated with degradation of
      laminin. These ischemia-induced extracellular events coincide temporarily with
      proteolytic modification of FAK protein and diminished level of its
      phosphorylated form, to about 50% of the initial value. These results are
      indicative of an involvement of ECM-pp125(FAK) signaling pathway in ischemia
      induced neuronal degeneration.

PMID- 12788515
TI  - The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-alpha
      induced alterations to monoamine turnover in prefrontal cortex and hippocampus.
AB  - Interferon-alpha (IFN-alpha) administration induces major depression in a
      significant number of patients undergoing treatment for viral illnesses and other
      chronic diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to
      counteract a number of IFN-alpha-induced side effects, including pro-inflammatory
      cytokine activation and stress hormone release. To investigate this possibility
      further, we sought to determine the effect of the NSAID diclofenac sodium on
      monoamine turnover in brain induced by acute IFN-alpha exposure. Eleven male,
      Wistar rats (8 weeks old) were pretreated with diclofenac (20 mg/kg, s.c.) or
      saline, followed by intracerebroventricular (i.c.v.) infusion of IFN-alpha (1000
      IU in 5 microl) or vehicle. The prefrontal cortex, striatum, and hippocampus were
      isolated and samples were assayed for monoamines and major metabolites by high
      pressure liquid chromatography with electrochemical detection. The data show that
      acute IFN-alpha increased serotonin turnover in prefrontal cortex and increased
      dopamine turnover in hippocampus, while pre-treatment with diclofenac completely
      prevented these neurochemical responses. Importantly, these changes were recorded
      in two brain areas known to be important in depression and antidepressant action.
      These data offer support for a novel role of NSAIDs in modulating IFN-alpha
      induced neurochemical alterations, and raise the possibility of the use of NSAIDs
      for the prevention of IFN-alpha-induced depression.

PMID- 12788516
TI  - Cardiovascular responses and neurotransmitter changes following blockade of nNOS
      within the ventrolateral medulla during static muscle contraction.
AB  - Nitric oxide (NO) is synthesized from L-arginine through the activity of the
      synthetic enzyme, NO synthase (NOS). Previous studies have demonstrated the roles
      of the three isoforms of NOS, namely endothelial NOS (eNOS), neuronal NOS (nNOS),
      and inducible NOS (iNOS) in cardiovascular regulation. However, no investigation
      has been done to study their individual role in modulating cardiovascular
      responses during static skeletal muscle contraction. In this study, we determined
      the effects of microdialyzing a specific nNOS antagonist into the rostral (RVLM)
      and caudal ventrolateral medulla (CVLM) on cardiovascular responses and
      glutamatergic/GABAergic neurotransmission during the exercise pressor reflex
      using rats. We hypothesized that the NO modulation of the exercise pressor reflex
      was largely influenced by specific nNOS activity within the ventrolateral
      medulla. Bilateral microdialysis of a selective nNOS antagonist, 1-(2
      trifluoromethylphenyl)-imidazole (1.0 microM), for 30 or 60 min into the RVLM
      potentiated cardiovascular responses and glutamate release during a static muscle
      contraction. Levels of GABA within the RVLM were decreased. The cardiovascular
      responses and neurochemical changes to muscle contraction recovered following
      discontinuation of the drug. In contrast, bilateral application of the nNOS
      antagonist into CVLM attenuated cardiovascular responses and glutamate release
      during a static muscle contraction, but augmented GABA release. These results
      demonstrate that nNOS in the ventrolateral medulla plays an important role in
      modulating glutamatergic/GABAergic neurotransmission that regulates the exercise
      pressor reflex, and contributes to the sympathoexcitatory and sympathoinhibitory
      actions of NO within the RVLM and CVLM, respectively.

PMID- 12788517
TI  - Bovine subcommissural organ displays spontaneous and synchronous intracellular
      calcium oscillations.
AB  - The subcommissural organ (SCO) is an ependymal brain gland that secretes into the
      cerebrospinal fluid glycoproteins that polymerize, forming Reissner's fiber (RF).
      The SCO-RF complex seems to be involved in vertebrate nervous system development,
      although its role in adults is unknown. Furthermore, its physiology is still
      greatly undetermined, and little is known about the release control of SCO
      secretion and the underlying intracellular mechanisms. In this report, we show
      that up to 90% of 3-5-day-old in vitro SCO cells from both intact and partially
      dispersed SCO explants displayed spontaneous cytosolic Ca2+ oscillations. The
      putative role of these spontaneous calcium oscillations in SCO secretory activity
      is discussed taking into consideration several previous findings. Two distinct
      subpopulations of SCO cells were detected, each one containing cells with
      synchronized calcium oscillations. A possible existence of different functional
      domains in SCO is therefore discussed. Oscillations persisted in the absence of
      extracellular Ca2+, indicating the major involvement of Ca2+ released from
      internal stores. Depolarization failed to induce intracellular calcium increases,
      although it disturbed the oscillation frequency, suggesting a putative modulator
      role of depolarizing agonists on the calcium oscillating pattern through voltage
      gated calcium channels. Carbachol, a cholinergic agonist, evoked a switch in Ca2+
      signaling from a calcium oscillating mode to a sustained and increased
      intracellular Ca2+ mode in 30% of measured cells, suggesting the involvement of
      acetylcholine in SCO activity, via a calcium-mediated response.

PMID- 12788518
TI  - Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in
      mice.
AB  - Acute administration of intraperitoneal and oral guanosine has been shown to
      prevent quinolinic acid and alpha-dendrotoxin-induced seizures in rats and mice.
      In this study, we investigated the effects of 2 weeks ad libitum consumption of
      guanosine (0.5 mg/ml) added to mice water supply on seizures and lethality
      induced by the alpha-dendrotoxin, hole-board behavior, inhibitory avoidance task,
      locomotor activity, motor coordination, rectal temperature, body weight, and
      water and food consumption. Guanosine prevented seizures in 40% and death in 50%
      on mice treated with i.c.v. alpha-dendrotoxin; it also impaired inhibitory
      avoidance memory and increased head-dipping behavior and locomotor activity on
      the hole-board test. Guanosine consumption did not alter any of the other
      parameters evaluated. The anticonvulsant, amnesic, and anxyolytic-like effects
      may be associated with the ability of guanosine in modulating the glutamatergic
      excitatory system. Adding to previously reported data, these findings suggest a
      potential role for chronic guanosine in the management of diseases associated
      with glutamatergic excitotoxicity, including epilepsy and anxiety.

PMID- 12788519
TI  - Role of oleic acid as a neurotrophic factor is supported in vivo by the
      expression of GAP-43 subsequent to the activation of SREBP-1 and the up
      regulation of stearoyl-CoA desaturase during postnatal development of the brain.
AB  - We have recently reported that albumin, a serum protein present in the developing
      brain, stimulates the synthesis of oleic acid by cultured astrocytes by inducing
      stearoyl-CoA 9-desaturase, the rate-limiting enzyme in oleic acid synthesis,
      through activation of the sterol regulatory element-binding protein-1. In this
      work, we offer evidence supporting the in vivo occurrence of this process during
      the postnatal development of the rat brain. Our results show that albumin reaches
      maximal brain level by day 1 after birth, coinciding with activation of the
      sterol response element binding protein-1, which is responsible for the
      transcription of the enzymes required for oleic acid synthesis. In addition, the
      developmental profile of stearoyl-CoA 9-desaturase-1 mRNA expression follows that
      of sterol regulatory element-binding protein-1 activation, indicating that these
      phenomena are tightly linked. In a previous work, we showed that oleic acid
      induces neuronal differentiation, as indicated by the expression of growth
      associated protein-43. Here, we report that the expression of growth associated
      protein-43 mRNA peaks at about day 7 after birth, following the maximal
      expression of stearoyl-CoA 9-desaturase-1 mRNA that occurs between days 3 and 5
      postnatally. In conclusion, our results support the hypothesis that the synthesis
      of oleic acid is linked to neuronal differentiation during rat brain development.

PMID- 12788520
TI  - Differential increases in P2X receptor levels in rat vagal efferent neurones
      following a vagal nerve section.
AB  - Extracellular ATP can influence cells via activation of P2X purinoceptors, the
      distribution of which can be altered in the central and peripheral nervous
      systems following injury or tissue damage. Here we have investigated the effect
      of a unilateral section of the cervical vagus nerve on the distribution of
      P2X(1), P2X(2), P2X(3), P2X(4) and P2X(7) receptor subunit immunoreactivity (R
      IR) in the dorsal vagal motor nucleus (DVN) and the nucleus ambiguus (NA) in the
      medulla oblongata. As early as 2 days, and followed up to 14 days, there was a
      dramatic ipsilateral increase in P2X(1), P2X(2) and P2X(4)R-IR in the cell soma
      of vagal efferent neurones in the DVN following the nerve section, but not the
      NA. There were no changes in P2X(3) and P2X(7)R-IR in either nuclei. To test for
      possible functional consequences of increased P2X receptor levels, whole-cell
      patch-clamp recordings were made from DVN cells in brainstem slices 4 days
      following unilateral vagotomy. Application of ATP revealed large cell-to-cell
      variance in the current amplitude in neurones from both sectioned and control
      DVN. However, when ATP responses were compared to those elicited by the nicotinic
      acetylcholine receptor agonist carbachol, the mean ratio of the peak ATP-evoked
      current to the peak carbachol-evoked current was significantly larger in DVN
      neurones ipsilateral to the section. Thus the increase in P2XR levels in DVN
      cells ipsilateral to a nerve section are likely to reflect an increase in
      expression of functional P2XRs on the cell surface.

PMID- 12788521
TI  - Anticonvulsant dicarboxyphenylglycines differentially modulate excitatory amino
      acid release in the rat cerebral cortex.
AB  - The 3,4-dicarboxyphenylglycines (3,4-DCPGs) have recently been shown to be
      effective new anticonvulsant agents in a rodent model of epilepsy, with the
      racemic mixture showing significantly greater potency than either isomer alone.
      The (R)-isomer has been identified as a competitive AMPA-type ionotropic
      glutamate receptor antagonist, whilst (S)-3,4-DCPG is a highly potent and
      selective metabotropic glutamate receptor 8 (mGlu8 receptor) agonist. We now
      report the inhibitory activity of (R)- and (RS)-3,4-DCPG, but not (S)-3,4-DCPG,
      against both 35 mM and 50 mM KCl-evoked glutamate release in the rat cerebral
      cortex in vitro. In contrast to the anticonvulsant actions of the 3,4-DCPGs, no
      evidence was obtained for a synergistic inhibitory interaction between the
      separate isomers. We conclude that whilst inhibition of cortical excitatory amino
      acid release may contribute to the anticonvulsant actions of (RS)-3,4-DCPG, it
      does not represent the sole mechanism of action. Synergistic interactions between
      ligands acting at different subtypes of ionotropic and metabotropic glutamate
      receptors remains a promising new strategy for the treatment of currently drug
      refractory seizure states.

PMID- 12788522
TI  - Procaine impairs learning and memory consolidation in the honeybee.
AB  - In vertebrates local anaesthetics lead to various learning deficits, depending on
      the site and time of injection. In this study we show the effects of the local
      anaesthetic procaine on learning and memory in an invertebrate, the honeybee.
      Reversible blocking of neuronal processes leads to different memory deficits
      depending on the time window during which the local anaesthesia is in effect.

PMID- 12788523
TI  - Predominant effects of Polypodium leucotomos on membrane integrity, lipid
      peroxidation, and expression of elastin and matrixmetalloproteinase-1 in
      ultraviolet radiation exposed fibroblasts, and keratinocytes.
AB  - BACKGROUND: Polypodium leucotomos has been reported to have antioxidant, anti
      inflammatory and photoprotective properties. Exposure of skin to ultraviolet (UV)
      radiation can lead to deposition of excessive elastotic material, reduction in
      collagen, and increased expression of matrix metalloproteinases (MMPs).
      OBJECTIVE: The goal of this research was to determine the effects of P.
      leucotomos in the absence or presence of UVA or UVB radiation on membrane damage,
      lipid peroxidation, and expression of elastin and MMP-1 in fibroblasts and
      keratinocytes, respectively. METHODS: Fibroblasts and keratinocytes,
      respectively, were irradiated by a single exposure to UVA (0.6, 1.8 or 3.6 J) or
      UVB radiation (0.75, 2.5 or 7.5 mJ), and then incubated with, or without, P.
      leucotomos (0.01, 0.1 and 1%) and examined for membrane damage, lipid
      peroxidation, expression of elastin (protein levels) and MMP-1 (protein levels or
      MMP-1 promoter activity). RESULTS: UV radiation did not significantly alter
      membrane integrity, lipid peroxidation or MMP-1 expression, but increased elastin
      expression. P. leucotomos significantly improved membrane integrity, inhibited
      lipid peroxidation, increased elastin expression, and inhibited MMP-1 expression
      in both fibroblasts, and keratinocytes. The effects of P. leucotomos predominated
      in the presence of UVA or UVB in both fibroblasts and keratinocytes,
      respectively, with the exception of inhibition of MMP-1 protein levels in
      fibroblasts only in combination with UV radiation. CONCLUSION: Lower
      concentration of P. leucotomos (lower than 0.1%), may be beneficial in preventing
      photoaging by improving membrane integrity and inhibiting MMP-1, without
      increasing elastin expression. Higher concentration (greater than 0.1%) of P.
      leucotomos may reverse the loss of normal elastic fibers associated with
      intrinsic aging.

PMID- 12788524
TI  - A mutation in the connexin 30 gene in Chinese Han patients with hidrotic
      ectodermal dysplasia.
AB  - BACKGROUND: hidrotic ectodermal dysplasia (HED) or Clouston syndrome is a rare
      autosomal dominant disorder affecting the skin and its derivatives. It is
      characterized by the triad of nail dystrophy, alopecia, and palmoplantar
      hyperkeratosis. To date, all mutations have been involving in three codons: G11R,
      A88V and V37E in the connexin 30 (Cx30) gene have been shown to cause this
      disorder. OBJECTIVE: in order to analyze the mutations of the Cx30 gene in
      Chinese Han patients with HED. METHODS: we collected a large Chinese HED family
      consisting of a total of 81 individuals including 28 HED patients (14 males and
      14 females). The whole coding region of Cx30 was amplified by polymerase chain
      reaction and products analyzed by direct sequencing, then further confirmed at
      the mRNA level by RT-PCR. RESULTS: we detected a transition, 31(G-->A), leading
      to a missense mutation (G11R) in genomic DNAs of 18 patients, and the point
      mutation was not found in 16 normal individuals in this HED family and in 188
      unrelated, population-match control individuals. The transcription of mutated
      allele was confirmed by RT-PCR of Cx30 mRNA. CONCLUSION: our data suggests that a
      G11R missense mutation in the Cx30 gene can cause HED in Chinese Han population
      and emphasizes the importance of screening for this as well as other Cx30 gene
      mutations in the HED.

PMID- 12788526
TI  - Rapid identification of Trichophyton tonsurans by PCR-RFLP analysis of ribosomal
      DNA regions.
AB  - BACKGROUND: Culture morphology of Trichophyton (T.) tonsurans, an emerging
      pathogen of dermatophytosis in Japan, varies widely and species level
      identification is sometimes very difficult. Reliable molecular markers are
      expected to be introduced for their identification. OBJECTIVE: The present study
      was conducted to evaluate the efficacy of restriction fragment length
      polymorphism (RFLP) analysis of PCR amplified ribosomal (r) DNA including
      internal transcribed spacers (ITS), as an identification tool. METHODS: Total
      cellular DNA was extracted from 26 Japanese isolates of T. tonsurans, along with
      several taxa of the members in the T. mentagrophytes complex, T. rubrum, T.
      violaceum and Epidermophyton floccosum, using a mini-preparation method. PCR
      amplicons were digested with restriction enzymes Mva I or Hinf I, then
      electrophoresed on 5% polyacrylamide gel. RESULTS: The banding profiles were
      observed about 8 h from initiating DNA extraction. Intraspecies polymorphism was
      not detected among T. tonsurans isolates, and their profiles obtained using Mva I
      digestion were clearly different from those of the other dermatophyte species.
      The restriction profiles evaluated from nucleotide sequence of the regions by a
      computer analysis were compatible with the electrophoresed profiles on gel.
      CONCLUSION: PCR-RFLP analysis is a rapid and reliable tool for the identification
      of T. tonsurans.

PMID- 12788525
TI  - IFN-gamma fails to antagonize fibrotic effect of TGF-beta on keloid-derived
      dermal fibroblasts.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) has been noted as a potential
      therapeutic agent for various fibrotic disorders, in part, through its
      antagonistic effect on a fibrogenic cytokine, transforming growth factor-beta
      (TGF-beta). Keloid is a fibrotic skin disorder that results in an excessive
      deposition of extracellular matrix, which is associated with altered-expression
      of or -responses to TGF-beta in dermal fibroblasts. OBJECTIVE: We sought to
      determine whether IFN-gamma antagonized TGF-beta-mediated fibrotic response in
      keloid-derived dermal fibroblasts. METHODS: Type I collagen production,
      fibroblast contractile activity, and alpha-smooth muscle actin (alpha-SMA)
      expression were assessed by using Western blotting, an in vitro type I collagen
      gel contraction assay, and immunofluorescence study in normal and keloid-derived
      human dermal fibroblasts in the presence or absence of IFN-gamma and/or TGF-beta.
      RESULTS: In contrast to normal dermal fibroblasts, IFN-gamma did not inhibit TGF
      beta-induced type I collagen production, contractile activity, and alpha-SMA
      expression in keloid-derived dermal fibroblasts. In addition, keloid-derived
      dermal fibroblasts constitutively expressed type I collagen and alpha-SMA with
      increased capacity to contract a collagen matrix. CONCLUSION: IFN-gamma failed to
      antagonize TGF-beta-mediated fibrotic response in keloid-derived dermal
      fibroblasts. Thus, IFN-gamma may not be therapeutically useful for keloid and
      clarification of the molecular mechanisms underlying the IFN-gamma resistance
      should be investigated for therapeutic application of IFN-gamma for keloid.

PMID- 12788527
TI  - Comparative study of autoantigen profile between Colombian and Brazilian types of
      endemic pemphigus foliaceus by various biochemical and molecular biological
      techniques.
AB  - BACKGROUND: Besides Brazilian endemic pemphigus foliaceus (EPF), we have
      described another focus of EPF in Colombia. Our previous study suggested that
      Colombian EPF seemed to react various plakin family proteins, such as envoplakin,
      periplakin and BP230. OBJECTIVE: To further characterize the Colombian EPF and
      study the difference from Brazilian EPF, we examined the antigen profile of the
      two types of EPF. METHODS AND RESULTS: Immunoblotting using normal human
      epidermal extracts revealed that 38% Colombian EPF sera and 25% Brazilian EPF
      sera showed IgG antibodies reactive with desmoglein (Dsg) 1, pemphigus foliaceus
      antigen. The sera of both types of EPF showed protein bands co-migrating with
      plakin family proteins, particularly periplakin. Immunoblotting analyses using
      recombinant proteins of various domains of envoplakin, periplakin and BP230
      revealed that a considerable number of Colombian EPF sera reacted with
      recombinant proteins of periplakin, while only few Brazilian sera reacted with
      some of the recombinant proteins of any plakins. Enzyme-linked immunosorbent
      assay (ELISA) for Dsg1 and Dsg3 showed that Dsg1 was reacted by almost all sera
      of both types of EPF. However, unexpectedly, while none of Colombian EPF sera
      reacted with Dsg3, about half of Brazilian EPF sera reacted with Dsg3.
      CONCLUSION: These results suggested that the Colombian EPF is basically similar
      to Brazilian EPF in terms that major antigen is Dsg1, but there were some
      different antigen profiles between the two types of EPF.

PMID- 12788528
TI  - Different mechanisms of adhesion molecule expression in human dermal
      microvascular endothelial cells by xanthoma tissue-mediated and copper-mediated
      oxidized low density lipoproteins.
AB  - BACKGROUND: Oxidation of low density lipoprotein (LDL) has been implicated in
      infiltration of foam cells derived from circulating monocytes. Monocyte adhesion
      to endothelial cells and migration into dermis are essential steps for
      infiltration of foam cells. OBJECTIVE: We investigated the role of adhesion
      molecules contributing to the process of monocyte adhesion to human dermal
      microvascular endothelial cells (HDMEC). Special attention was paid to the signal
      transduction for adhesion molecule expression induced by two distinct types of
      oxidized LDL. METHODS: HDMEC were incubated with xanthoma tissue-modified LDL (x
      LDL), a model of extravasated LDL oxidized in xanthoma lesions, or Cu(2+)-treated
      LDL (Cu-LDL), a model of oxidized LDL. Adhesion of U937 cells, a human monocytic
      leukemia cell line, to HDMEC and expression of endothelial cell adhesion
      molecules on HDMEC were examined. Signal transduction pathways for the adhesion
      molecule expression were evaluated by employing specific inhibitors. RESULTS: x
      LDL induced adhesion of U937 cells to HDMEC through vascular cell adhesion
      molecule-1 (VCAM-1) and E-selectin by activating tyrosine kinase pathway. Cu-LDL
      up-regulated the adhesion through not only VCAM-1 and E-selectin but also
      intercellular cell adhesion molecule-1 (ICAM-1) by activating G(i) protein
      pathway. CONCLUSION: Extravasated and oxidized LDL in xanthoma lesions
      contributes to foam cell recruitment by activating tyrosine kinase pathway and
      inducing adhesion of monocytes to HDMEC through VCAM-1 and E-selectin. Cu-LDL, on
      the other hand, activates G(i) protein pathway and induces the adhesion through
      ICAM-1, VCAM-1 and E-selectin.

PMID- 12788529
TI  - Urokinase-type plasminogen activator is activated in stratum corneum after
      barrier disruption.
AB  - The plasminogen/plasmin system in epidermis is thought to be the major protease
      involved in the delay of barrier recovery. However, little is known about the
      mechanism through which this system is activated. In order to clarify this
      mechanism, we first determined the distribution of proteolytic activity by using
      in situ zymography. As a result, plasminogen-activator activity was found to be
      present in the stratum corneum (SC) after barrier disruption. Next, SC subjected
      to repeated barrier disruption was collected to identify the protease. The
      protease was identified as urokinase-type plasminogen activator, because
      flybrinolytic activity of the collected SC was abolished by addition of anti
      urokinase antibody. Urokinase activation in SC was confirmed by means of an in
      vitro assay, in which the precursor of urokinase (pro-uPA) became active after
      incubation with the insoluble component of SC homogenate. These findings
      indicated that urokinase-type plasminogen activator is activated in SC after
      barrier disruption and this activation might trigger the plasminogen/plasmin
      system in the epidermis.

PMID- 12788530
TI  - Cicatricial pemphigoid sera specifically react with the most C-terminal portion
      of BP180.
AB  - BACKGROUND: cicatricial pemphigoid and bullous pemphigoid are characterized by
      circulating autoantibodies to the hemidesmosomal protein, BP180. Different
      clinical features between cicatricial pemphigoid and bullous pemphigoid appear to
      correlate with distinct target epitopes on BP180. Previous studies demonstrated
      that the majority of bullous pemphigoid sera react with immunodominant membrane
      proximal non-collagenous domain (NC16a) on the extracellular portion of BP180,
      whereas cicatricial pemphigoid antibodies are directed to the C-terminal domains
      of BP180. However, the fine sites within the C-terminal domain of BP180
      recognized by autoantibodies in patients with cicatricial pemphigoid and bullous
      pemphigoid have not yet been clearly elucidated. OBJECTIVES: the aim of the
      present study was to analyze the fine specificity of the reactivity within the C
      terminal domain of BP180 for the autoantibodies in sera from patients with
      cicatricial pemphigoid, and to compare the reactivity with that of bullous
      pemphigoid sera. METHODS AND RESULTS: we generated three recombinant proteins
      with 101 amino acids, which together cover the C-terminal domain of BP180. We
      confirmed that cicatricial pemphigoid sera mainly react with most C-terminal
      portion, whereas bullous pemphigoid sera react with more N-terminal domains.
      CONCLUSION: this study implicated that autoantibodies of sera from patients with
      cicatricial pemphigoid and bullous pemphigoid reacted differently within C
      terminal domain of BP180.

PMID- 12788531
TI  - Analysis of hepatitis C virus (HCV) RNA in the lesions of lichen planus in
      patients with chronic hepatitis C: detection of anti-genomic- as well as genomic
      strand HCV RNAs in lichen planus lesions.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a single-strand RNA virus. The association
      of lichen planus with chronic HCV infection has been reported, as has been
      cryoglobulinemic purpura, psoriasis, urticaria, and porphyria cutanea tarda.
      However, the cause of lichen planus is unclear. OBJECTIVES: To investigate
      whether genomic- and/or anti-genomic-strand HCV RNAs are present in the lichen
      planus lesions of chronic hepatitis C patients and to elucidate the pathogenesis
      of lichen planus. METHODS: Reverse transcription-polymerase chain reaction (RT
      PCR) followed by nested-PCR was carried out to detect HCV RNA using RNA samples
      from lichen planus lesions of three patients with chronic hepatitis C. Since it
      is well known that commonly there is relatively dense inflammatory cell
      infiltration mainly in the upper dermis in lichen planus, the same RT-PCR
      procedure was performed using RNA from peripheral blood leukocytes from the same
      patients. In addition, in one patient, the same procedure was also performed
      using an RNA sample from normal skin. RESULTS: Bands of the appropriate size (161
      base pairs corresponding to region 98-258 of HCV RNA) in the nested-PCR products
      for both genomic- and anti-genomic-strands were detected in lichen planus lesions
      as well as in peripheral blood leukocytes in all the cases. CONCLUSION: To the
      best of our knowledge, this is the first report showing the presence of anti
      genomic- as well as genomic-strand HCV RNAs in lichen planus lesions in patients
      with chronic hepatitis C; suggesting that HCV-associated lichen planus lesions
      may be sites of HCV replication.

PMID- 12788532
TI  - The CUSP DeltaNp63alpha isoform of human p63 is downregulated by solar-simulated
      ultraviolet radiation.
AB  - BACKGROUND: In normal human keratinocytes, a p53-like protein, DeltaNp63alpha,
      also known as CUSP, is constitutively and abundantly expressed. The significant
      constitutive expression of DeltaNp63alpha in stratified epithelium has been
      proposed to maintain the proliferative capacity of basal cells, blocking the
      consequences of inappropriate p53 activation. OBJECTIVE: To determine the
      response of keratinocyte DeltaNp63alpha to ultraviolet radiation (UVR), a
      stimulus for p53 activation. METHODS: Cultured normal human keratinocytes were
      exposed to graded doses of solar-simulated UVR. The expression of DeltaNp63alpha
      protein and mRNA were measured with Western and Northern blotting. Normal mouse
      skin was exposed to UVR, and DeltaNp63alpha expression assessed with
      immunohistochemistry. RESULTS: Increasing doses of UVR virtually shut off
      DeltaNp63alpha protein and mRNA expression in cultured normal human keratinocytes
      and in normal mouse skin in vivo. CONCLUSION: This study supports the hypothesis
      that in situations where p53 activation is desirable, as with DNA-damaging UVR,
      DeltaNp63alpha downregulation occurs and may possibly allow for better target
      gene transcription by p53.

PMID- 12788534
TI  - Nuclear transport: an emerging opportunity for drug targeting.

PMID- 12788533
TI  - Hypoxia-induced increase of matrix metalloproteinase-1 synthesis is not restored
      by reoxygenation in a three-dimensional culture of human dermal fibroblasts.
AB  - BACKGROUND: Delayed wound healing is multi-factorial. Although ischemic change is
      considered to be crucial, little is known about the effects of hypoxia or
      reoxygenation on the connective tissue metabolism by human dermal fibroblasts.
      OBJECTIVE: The aim of this study is to determine whether or not hypoxia (2% O(2))
      or reoxygenation (20% O(2)) affects mRNA expression and production of matrix
      metalloproteinase-1 (MMP-1), type I collagen, tissue inhibitors of
      metalloproteinase-1 (TIMP-1), and transforming growth factor-beta1 (TGF-beta1) by
      human dermal fibroblasts in a three-dimensional culture. METHODS: We introduced
      the three-dimensional culture of human dermal fibroblasts with experimental
      wound. After wounding, cells were incubated under hypoxic (2%) or normoxic (20%)
      condition, and harvested at 24, 36, 48, and 72 h (n=8). In the reoxygenation
      study (n=4), cells were first exposed to a hypoxic condition for 72 h and further
      incubated under a normoxic condition for 72 h. RESULTS: The relative ratio
      (hypoxia/normoxia) of MMP-1 mRNA expressions were significantly elevated at 36
      and 48 h compared with those at 12 h (P<0.05). The relative ratio of proMMP-1 was
      also significantly increased at 48 and 72 h compared with that at 12 h (P<0.001
      and P<0.05, respectively). There were no significant changes in mRNA and protein
      levels of type I collagen, TGF-beta1, and TIMP-1. In a reoxygenic condition, 72 h
      reoxygenation after 72 h hypoxia, the hypoxia-induced alterations of MMP-1 and
      carboxyterminal propeptide of type I procollagen (PIP) were not restored.
      CONCLUSION: Our results indicate that hypoxia may be responsible for delayed
      wound healing by inducing an increase of MMP-1 synthesis.

PMID- 12788535
TI  - Mechanisms of nuclear transport and interventions.
AB  - One of the more overlooked aspects of drug action and delivery is the
      exploitation of nucleocytoplasmic shuttling. Eukaryotic cells regulate many
      biological processes by the compartmentation of specific proteins into designated
      areas. Drugs that have a direct effect on a single protein must be able to
      localize to the same site as the protein and interact with one or more of its
      domains. Alternatively, a drug that effectively blocks the target protein from
      reaching its proper organelle can also inhibit the protein's function. Exploiting
      the selective movement of macromolecules across the nuclear envelope represents
      an exciting new area of drug development. This review aims to explain the basic
      nuclear import/export pathways while focusing on the known drugs that alter the
      regulation of nucleocytoplasmic trafficking.

PMID- 12788536
TI  - Molecular mechanisms that regulate transcription factor localization suggest new
      targets for drug development.
AB  - The distinctive nuclear and cytoplasmic compartments of a eukaryote cell requires
      that metabolic processes which occur in the nucleus, such as gene transcription,
      are coordinated with related processes which occur in the cytoplasm. The steady
      state nuclear abundance of many transcription factors is the net outcome of a
      dynamic balance between nuclear import and nuclear export. Nuclear import and
      nuclear export mechanisms that govern the nucleocytoplasmic distribution of
      transcription factors are regulated at multiple levels, including post
      translational modifications that alter the accessibility of cis-acting transport
      signals, binding and release from compartment-specific anchors, and the selective
      utilization of specific transport factors or specific nucleoporins. The net
      nuclear abundance of a transcription factor represents the integrated sum of
      multiple signal transduction pathways. Mechanisms that regulate nucleocytoplasmic
      transport of transcription factors may provide novel opportunities for drug
      development.

PMID- 12788537
TI  - Virus nuclear import.
AB  - Many viruses replicate in the nucleus of their host cells. To gain access to this
      compartment, they must navigate their way from the cell surface, through the
      endosomal or plasma membrane, across a crowded cytoplasm and finally cross the
      nuclear envelope. Entry into the nucleus typically occurs via nuclear pores,
      which have a strict size limit that most viruses cannot traverse without prior
      uncoating or disassembly. While the majority of the viruses make use of the
      cellular nuclear import machinery for their nuclear transport, a growing number
      of viruses seem to use specialized, virus-encoded routes of nuclear import. For
      nuclear-replicating viruses, entry into the nucleus is highly dependent on prior
      trafficking and uncoating events that act to prime the virus genome for its final
      destination.

PMID- 12788538
TI  - Emerging significance of plasmid DNA nuclear import in gene therapy.
AB  - The signal-mediated import of plasmid DNA (pDNA) into nondividing mammalian cell
      nuclei is one of the key biological obstacles to nonviral therapeutic pDNA
      delivery. Overcoming this barrier to pDNA transfer is thus an important
      fundamental objective in gene therapy. Here, we outline the rationale behind
      current and future strategies for signal-mediated pDNA nuclear import. Results
      obtained from studies of the nuclear delivery of pDNA coupled to experimentally
      defined nuclear localisation signal (NLS) peptides, in conjunction with detergent
      permeabilised reconstitution cell assays, direct intracellular microinjection,
      cell-based transfection, and a limited number of in vivo experiments are
      discussed.

PMID- 12788539
TI  - Role of the cytoskeleton in nuclear import.
AB  - The role of the cytoskeleton in regulating the intracellular localization of
      cellular organelles, viruses, and individual proteins has been the subject of
      much investigation in recent years. While regulated transport through the nuclear
      pore remains the primary determinant of nuclear localization, it has become clear
      that the nuclear localization of viruses and some cellular proteins is mediated
      by the ability of the cytoskeleton, usually microtubules, to direct their
      perinuclear accumulation in close proximity to the nuclear pore complex. We also
      discuss how the size of virions and the viscous nature of the cytoplasm would
      make it very unlikely or even impossible for viruses to achieve this localization
      by diffusion alone in the absence of active transport mechanisms. This review
      focuses on the known methods employed by different viruses and proteins to effect
      their perinuclear accumulation.

PMID- 12788540
TI  - Noninvasive imaging of protein-protein interactions in living organisms.
AB  - Genomic research is expected to generate new types of complex observational data,
      changing the types of experiments as well as our understanding of biological
      processes. The investigation and definition of relationships among proteins is
      essential for understanding the function of each gene and the mechanisms of
      biological processes that specific genes are involved in. Recently, a study by
      Paulmurugan et al. demonstrated a tool for in vivo noninvasive imaging of protein
      protein interactions and intracellular networks.

PMID- 12788541
TI  - Synthetic gene libraries: in search of the optimal diversity.
AB  - Directed evolution has proven to be an effective method for evolving proteins
      with desired properties. A key step is the creation of suitably diverse gene
      libraries. Two new methods for creating such libraries make sole use of
      synthesized oligonucleotides and allow researchers to tailor the diversity of a
      library with greater precision and create libraries with greater diversity than
      was previously possible. Such increased diversity appears to accelerate directed
      evolution.

PMID- 12788542
TI  - Transforming cyanobacteria into bioreporters of biological relevance.
AB  - Microbial bioreporters play an important role in environmental monitoring and
      ecotoxicology. Microorganisms that are genetically modified with reporter genes
      can be used in various formats to determine the bioavailability of chemicals and
      their effect on living organisms. Cyanobacteria are abundant in the
      photosynthetic biosphere and have considerable potential with regards to
      broadening bioreporter applications. Two recent studies described novel
      cyanobacterial reporters for the detection of environmental toxicants and iron
      availability.

PMID- 12788543
TI  - Improved evaluation of potential allergens in GM food.

PMID- 12788544
TI  - On the complete determination of biological systems.
AB  - The nascent field of systems biology ambitiously proposes to integrate
      information from large-scale biology projects to create computational models that
      are, in some sense, complete. However, the details of what would constitute a
      complete systems-level model of an organism are far from clear. To provide a
      framework for this difficult question it is useful to define a model as a set of
      rules that maps a set of inputs (e.g. descriptions of the cell's environment) to
      a set of outputs (e.g. the concentrations of all its RNAs and proteins). We show
      how the properties of a model affect the required experimental sampling and
      estimate the number of experiments needed to "complete" a particular model. Based
      on these estimates, we suggest that the complete determination of a biological
      system is a concrete, achievable goal.

PMID- 12788545
TI  - Building with a scaffold: emerging strategies for high- to low-level cellular
      modeling.
AB  - Computational cellular models are becoming crucial for the analysis of complex
      biological systems. An important new paradigm for cellular modeling involves
      building a comprehensive scaffold of molecular interactions and then mining this
      scaffold to reveal a hierarchy of signaling, regulatory and metabolic pathways.
      We review the important trends that make this approach feasible and describe how
      they are spurring the development of models at multiple levels of abstraction.
      Pathway maps can be extracted from the scaffold using "high-level" computational
      models, which identify the key components, interactions and influences required
      for more detailed "low-level" models. Large-scale experimental measurements
      validate high-level models, whereas targeted experimental manipulations and
      measurements test low-level models.

PMID- 12788546
TI  - From biological databases to platforms for biomedical discovery.
AB  - The use of high-throughput DNA sequencing and proteomic methods has led to an
      unprecedented increase in the amount of genomic and proteomic data. Application
      of computing technologies and development of computational tools to analyze and
      present these data has not kept pace with the accumulation of information. Here,
      we discuss the use of different database systems to store biological information
      and mention some of the key emerging computing technologies that are likely to
      have a key role in the future of bioinformatics.

PMID- 12788547
TI  - Exopolysaccharides from lactic acid bacteria: perspectives and challenges.
AB  - Some lactic acid bacteria (LAB) secrete a polysaccharide polymer. This
      extracellular polysaccharide, or "exopolysaccharide" (EPS), is economically
      important because it can impart functional effects to foods and confer beneficial
      health effects. LAB have a "Generally Recognized As Safe" (GRAS) classification
      and are likely candidates for the production of functional EPSs. Current
      challenges are to improve the productivity of EPSs from LAB and to produce EPSs
      of a structure and size that impart the desired functionality. The engineering of
      improvements in these properties will depend on a deep understanding of the EPS
      biosynthetic metabolism and of how the structure of EPSs relates to a functional
      effect when incorporated into a food matrix.

PMID- 12788548
TI  - Antibodies in proteomics I: generating antibodies.
AB  - The explosion in genome sequencing, and in subsequent DNA array experiments, has
      provided extensive information on gene sequence, organization and expression.
      This has resulted in a desire to perform similarly broad experiments on all the
      proteins encoded by a genome. Panels of specific antibodies, or other binding
      ligands, will be essential tools in this endeavour. Because traditional
      immunization will be unlikely to generate antibodies in sufficient quantity, and
      of the required quality and reproducibility, in vitro selection methods will
      probably be used. This review--the first of two--examines the strategies
      available for in vitro antibody selection. The second review discusses the
      adaptation of these methods to high throughput and the uses to which antibodies,
      once derived, can be put.

PMID- 12788549
TI  - The role of Lactobacillus buchneri in forage preservation.
AB  - In 1996 Wienberg and Muck proposed to implement Lactobacillus buchneri in silage
      starters. The main reason for the use of heterofermentative lactic acid bacteria
      is the increased stability of silages against deterioration by yeasts and moulds
      when exposed to air. In the following years, the unique activity of L. buchneri
      in silages was evaluated. It was proven that acetic acid formed from lactic acid
      by L. buchneri is solely responsible for the increased stability of silages.
      Recently, a novel metabolic pathway from lactic acid to acetic acid and 1,2
      propanediol was proposed.

PMID- 12788550
TI  - An immersible manometric sensor for measurement of humidity and enzyme mediated
      changes in dissolved gas.
AB  - An immersible manometric sensor was made by covering the gaseous cavity of a
      pressure transducer with a 1 microm controlled pore membrane. Transfer of gas
      across the membrane allowed the pressure transducer to record changes in humidity
      or dissolved gas when immersed in solution. By immersing the sensor in distilled
      water, atmospheric humidity could be estimated by the deficit of atmospheric
      vapor pressure from saturation. In another application of the sensor, CO(2) was
      monitored continuously. This was not possible in previous closed-reactor type
      manometric sensors, and may allow the new technology to be used in applications
      requiring continuous monitoring of a process or stream. By coupling the sensor
      with enzymes liberating or consuming dissolved gas, different chemicals could be
      estimated. Urea was estimated by first hydrolyzing it with urease and then
      measuring the resulting CO(2) gas in solution. Glucose was measured through its
      enzymatic oxidation by glucose oxidase. The sensitivity to urea over the range 0
      2.5 mM was about 1.02 kPa/mM, and the standard error was 0.086 mM. Due to the
      lower solubility of oxygen, the sensitivity to glucose in a range from 0 to 10
      microM was over 100 kPa/mM, with a standard error of only 0.76 microM. This
      sensitivity was not possible in closed-reactor type manometric sensors due to
      constraints of dimensioning the head space gas volume for reproducibility and
      effective mass transfer. The 90% rise times for the sensor ranged from about 1-60
      min for the different applications. The dynamic characteristics of the device may
      be improved by using a membrane with greater porosity, higher rigidity and lower
      thickness, and by reducing the dimensions of the cavity volume in the sensor
      through integrated microfabrication of the membrane onto the transducer.

PMID- 12788551
TI  - An amperometric bi-enzyme sensor for determination of formate using cofactor
      regeneration.
AB  - A biosensor for detection of formate at submicromolar concentrations has been
      developed by co-immobilizing formate dehydrogenase (FDH, E.C. 1.2.1.2),
      salicylate hydroxylase (SHL, E.C. 1.14.13.1) and NAD(+) linked to polyethylene
      glycol (PEG-NAD(+)) in a poly(vinyl alcohol) (PVA) matrix in front of a Clark
      electrode. The principle of the bi-enzyme scheme is as follows: formate
      dehydrogenase converts formate into carbon dioxide using PEG-NAD(+).
      Corresponding PEG-NADH produced is then oxidized to PEG-NAD(+) by salicylate
      hydroxylase using sodium salicylate and oxygen. The oxygen consumption is
      monitored with the Clark-electrode. The advantages of this biosensor approach are
      the effective re-oxidation of PEG-NADH, and the entrapment of PEG-NAD(+)
      resulting in avoiding the addition of expensive cofactor to the working medium
      for each measurement. This bi-enzyme sensor has achieved a linear range of 1-300
      microM and a detection limit of 1.98 x 10(-7) M for formate (S/N=3), with the
      response time of 4 min. The working stability is limited to 7 days due to the
      inactivation of the enzymes. Only sodium salicylate was needed in milli-molar
      amounts.

PMID- 12788552
TI  - Application of a flow-type antibody sensor to the detection of Escherichia coli
      in various foods.
AB  - A flow-type biosensor system which uses a broad-spectrum anti-Escherichia coli
      antibody and quartz crystal microbalance as biological component and transducer
      was developed. Biosensor responses were initiated by injecting viable E. coli
      suspensions through a flow cell and the sensor system was optimized for response
      time according to flow rate and injection time, followed by the measurement of
      responses for various E. coli strains. As expected, the sensor system showed a
      characteristic broad binding feature against E. coli strains. A linear sensor
      response in double-logarithmic scale was observed for the microbial suspensions
      ranging from 1.7 x 10(5) to 8.7 x 10(7) CFU/ml. Sample measurements could be done
      within 20-30 min after Stomacher treatment followed by spiking or enrichment.

PMID- 12788553
TI  - Modification of ISFETs with a monolayer of latex beads for specific detection of
      proteins.
AB  - The so-called ion-step method is a novel potentiometric approach that can detect
      protein adsorbed onto the gate area of modified ion-sensitive field-effect
      transistors (ISFETs). In this report, a generic technology is described for
      immobilization of peptides and proteins to the ISFET gate in order to confer
      specific binding properties to the ISFET. For this, the surface of the ISFET was
      covered with a monolayer of Amino beads (diameter, 0.9 microm) followed by
      immobilization of protein ligands onto these beads. Amino beads are latex spheres
      that contain primary amino groups at the outer surface. Preactivation of the
      latex-bound amino groups with glutaraldehyde, and consecutive incubation with
      polylysine resulted in covalent immobilization of this polyamine, as revealed by
      ion stepping measurements. For ImmunoFET applications, human serum albumin (HSA)
      was immobilized onto the Amino bead-covered ISFETs, by passive adsorption but
      also by covalent coupling. Resulting devices were used for qualitative detection
      of alpha-HSA antibodies by means of the ion step method. The binding of antibody
      was very specific and fast (most of the binding was accomplished in 15 min) with
      signal yields up to 17 mV. Efforts to increase the antibody-binding capacity of
      the solid phase on the ISFET exploiting amino group activation (with
      glutaraldehyde or other homobifunctional cross linkers) before HSA coupling, did
      not improve signal yield. The bead technology described in this report is an
      easy, generic method for coating the ISFET with a solid phase that, using the ion
      step method, can be applied to immunosensing.

PMID- 12788555
TI  - Improved selectivity of microbial biosensor using membrane coating. Application
      to the analysis of ethanol during fermentation.
AB  - A ferricyanide mediated microbial biosensor for ethanol detection was prepared by
      surface modification of a glassy carbon electrode. The selectivity of the whole
      Gluconobacter oxydans cell biosensor for ethanol determination was greatly
      enhanced by the size exclusion effect of a cellulose acetate (CA) membrane. The
      use of a CA membrane increased the ethanol to glucose sensitivity ratio by a
      factor of 58.2 and even the ethanol to glycerol sensitivity ratio by a factor of
      7.5 compared with the use of a dialysis membrane. The biosensor provides rapid
      and sensitive detection of ethanol with a limit of detection of 0.85 microM
      (S/N=3). The selectivity of the biosensor toward alcohols was better compared to
      previously published enzyme biosensors based on alcohol oxidase or alcohol
      dehydrogenases. The biosensor was successfully used in an off-line monitoring of
      ethanol during batch fermentation by immobilized Saccharomyces cerevisiae cells
      with an initial glucose concentration of 200 g l(-1).

PMID- 12788554
TI  - A handheld real time thermal cycler for bacterial pathogen detection.
AB  - The handheld advanced nucleic acid analyzer (HANAA) is a portable real time
      thermal cycler unit that weighs under 1 kg and uses silicon and platinum-based
      thermalcycler units to conduct rapid heating and cooling of plastic reaction
      tubes. Two light emitting diodes (LED) provide greater than 1 mW of electrical
      power at wavelengths of 490 nm (blue) and 525 nm (green), allowing detection of
      the dyes FAM and JOE/TAMRA. Results are displayed in real time as bar graphs, and
      up to three, 4-sample assays can be run on the charge of the 12 V portable
      battery pack. The HANAA was evaluated for detection of defined Escherichia coli
      strains, and wild-type colonies isolated from stream water, using PCR for the lac
      Z and Tir genes. PCR reactions using SYBR Green dye allowed detection of E. coli
      ATCC 11775 and E. coli O157:H7 cells in under 30 min of assay time; however,
      background fluorescence associated with dye binding to nonspecific PCR products
      was present. DNA extracted from three isolates of Bacillus anthracis Ames, linked
      to a bioterrorism incident in Washington DC in October 2001, were also
      successfully tested on the HANAA using primers for the vrrA and capA genes.
      Positive results were observed at 32 and 22 min of assay time, respectively. A
      TaqMan probe specific to the aroQ gene of Erwinia herbicola was tested on the
      HANAA and when 500 cells were used as template, positive results were observed
      after only 7 min of assay time. Background fluorescence associated with the use
      of the probe was negligible. The HANAA is unique in offering real time PCR in a
      handheld format suitable for field use; a commercial version of the instrument,
      offering six reaction chambers, is available as of Fall 2002.

PMID- 12788556
TI  - Integrated capillary fluorescence DNA biosensor.
AB  - Covalent attachment of dsDNA molecules inside a glass capillary without the need
      for hybridization is described. It is shown that the glass capillary has a
      surface density of 2.5 x 10(13) molecules/cm(2) with specific binding capacity of
      62.5%. The resulting substrate was used to develop a biosensor for determining
      fluorescent organic analytes and metal binding with DNA. The biosensor combines
      highly specific immobilization chemistry with a capillary-geometry flow cell
      arrangement. The results show that fluorescent dyes are retained in the dsDNA
      modified surface and that exposure to concentrations of nickel and lead ions
      resulted in a recoverable, highly reproducible diminishment of the fluorescence
      intensity.

PMID- 12788557
TI  - Achieving differentiation of single-base mutations through hairpin
      oligonucleotide and electric potential control.
AB  - A novel assay for surface DNA hybridization, which is free of sample and probe
      labeling, convenient and of low cost, sensitive and capable of differentiation of
      single-base mutations, is reported. Hairpin oligonucleotides are carefully
      designed as probes and are covalently attached to Si chips. Segments of the human
      p53 gene are chosen to demonstrate the major features of the novel technique.
      Impedance measurement is used to detect the hybridization. To further optimize
      the performance, electric potential is applied on the chip. The apparently
      different responses of the chip to the complementary strand and the single-base
      mutant are shown under electric potential control. The criteria on the design of
      the hairpin oligonucleotides are discussed.

PMID- 12788558
TI  - Monitoring DNA hybridization on alkyl modified silicon surface through
      capacitance measurement.
AB  - Single strand oligodeoxynucleotide is attached to the alkyl modified silicon
      surface through a peptide bond. The oligodeoxynucleotide-modified silicon
      substrate is used as a working electrode in an electrochemical cell system. After
      the electrode is treated by a solution containing strands of complementary
      oligodeoxynucleotide the Mott-Schottky measurements exhibit obvious negative
      shift in the flat band potential of the electrode, while in a control experiment
      treated with a solution of non-complementary oligodeoxynucleotide such a shift
      does not occur. The DNA hybridization is also manifested in a real time
      capacitance measurement. A DNA sensor based on the capacitance measurement could
      be more convenient than that based on a fluorescence detection.

PMID- 12788559
TI  - HRP-based biosensor for monitoring rifampicin.
AB  - Pyrrole was electropolymerized onto a Pt electrode in the presence of LiClO(4)
      and horseradish peroxidase (HRP). This HRP-based biosensor has been used for the
      amperometric detection of rifampicin (RIF) in the presence of a constant
      concentration of H(2)O(2). The C(H(2)O(2)) as well as the applied potential
      (E(ap)) and the pH of the phosphate buffer have simultaneously been optimized
      through a central composite design. Under these conditions, repeatability,
      reproducibility, and stability of the modified electrode have been analyzed. The
      detection limit for RIF has been calculated taking into account the probability
      of false-positive (alpha) and -negative (beta), reaching a value of 5.06x10(-6)
      mol dm(-3). The biosensor was applied to the determination of RIF in
      pharmaceutical preparations and biological samples.

PMID- 12788560
TI  - Rapid and convenient determination of oxalic acid employing a novel oxalate
      biosensor based on oxalate oxidase and SIRE technology.
AB  - A new method for rapid determination of oxalic acid was developed using oxalate
      oxidase and a biosensor based on SIRE (sensors based on injection of the
      recognition element) technology. The method was selective, simple, fast, and
      cheap compared with other present detection systems for oxalate. The total
      analysis time for each assay was 2-9 min. A linear range was observed between 0
      and 5 mM when the reaction conditions were 30 degrees C and 60 s. The linear
      range and upper limit for concentration determination could be increased to 25 mM
      by shortening the reaction time. The lower limit of detection in standard
      solutions, 20 microM, could be achieved by means of modification of the reaction
      conditions, namely increasing the temperature and the reaction time. The
      biosensor method was compared with a conventional commercially available
      colorimetric method with respect to the determination of oxalic acid in urine
      samples. The urine oxalic acid concentrations determined with the biosensor
      method correlated well (R=0.952) with the colorimetric method.

PMID- 12788561
TI  - Covalently coupling the antibody on an amine-self-assembled gold surface to probe
      hyaluronan-binding protein with capacitance measurement.
AB  - Hyaluronan-binding proteins (HABPs), the important structural components of
      extracellular matrices, served important structural and regulatory functions
      during development and in maintaining adult tissue homestats. A sensitive,
      specific and rapid-responsing immunosensor to probe hyaluronan-binding cartilage
      protein was presented in this work. The novel immunosensor supplied a label-free
      detection method for HABP, which was based on measuring the capacitance change in
      between the unlabeled HABP (antigen) and rabbit-anti-HABP (Ra-HABP, antibody).
      The HABP immunosensor was prepared by covalently coupling Ra-HABP on an amine
      self-assembled gold surface with glutaraldehyde. The capacitance change
      corresponding to the concentration of HABP, the target antigen, was evaluated by
      an electrochemical approach called potentiostatic-step in microseconds. The
      immunosensor showed a specific response to HABP in the range 10-1000 ng/ml. The
      presented work supplied a promising clinical screening method.

PMID- 12788562
TI  - Highly sensitive biosensing using a supercritical angle fluorescence (SAF)
      instrument.
AB  - We present a new optical biosensor for probing molecular binding to a water/glass
      interface. The system is designed to measure the kinetics of surface reactions
      down to low analyte concentrations straightforwardly. The selective detection of
      surface bound fluorescence is achieved by collecting supercritical angle
      fluorescence (SAF) emission of surface bound molecules into the glass. Thereby
      the expansion of the detection volume into the aqueous probe is reduced to about
      one sixth of the fluorescence wavelength, consequently bulk fluorescence from the
      solution is rejected successfully. The SAF-signal is captured by a parabolic
      glass lens, which leads to high spatial collection efficiency and detection
      sensitivity. The sensor has an inverted optical design and is compatible with
      common glass cover slips, which strongly facilitates operation for the user
      working in the biological and biochemical fields. The performance of the system
      is demonstrated by real time measurements of antibody-antigen reactions. Rate
      constants of the reaction were extracted. Antigen concentrations were detected
      down to 10(-13) mol/l.

PMID- 12788563
TI  - A more challenging summit than Everest.

PMID- 12788564
TI  - Varicocele and infertility.

PMID- 12788565
TI  - Might the diabetic environment in utero lead to type 2 diabetes?

PMID- 12788566
TI  - Alternative lengthening of telomeres: dangerous road less travelled.

PMID- 12788567
TI  - The UK National DNA Database.

PMID- 12788568
TI  - Celebrating Everest.

PMID- 12788569
TI  - Effect of enalapril on 12-year survival and life expectancy in patients with left
      ventricular systolic dysfunction: a follow-up study.
AB  - BACKGROUND: In the studies of left ventricular dysfunction (SOLVD), enalapril
      reduced mortality in patients with symptomatic but not asymptomatic left
      ventricular systolic dysfunction during the trial. We did a 12-year follow-up of
      SOLVD to establish if the mortality reduction with enalapril among patients with
      heart failure was sustained, and whether a subsequent reduction in mortality
      would emerge among those with asymptomatic ventricular dysfunction. METHODS: Of
      the 6797 patients previously enrolled in the SOLVD prevention and treatment
      trials, we ascertained the subsequent vital status of 5165 individuals who were
      alive when the trials had been completed. Follow-up was done through direct
      contacts in Belgium and linkages with national death registries and federal
      beneficiary or historic tax summary files in the USA and Canada. FINDINGS: Follow
      up was 99.8% (6784/6797) complete. In the prevention trial, 50.9% (1074/2111) of
      the enalapril group had died compared with 56.4% (1195/2117) of the placebo group
      (generalised Wilcoxon p=0.001). In the treatment trial, 79.8% (1025/1285) of the
      enalapril group had died compared with 80.8% (1038/1284) of the placebo group
      (generalised Wilcoxon p=0.01). The reductions in cardiac deaths were significant
      and similar in both trials. When data for the prevention and treatment trials
      were combined, the hazard ratio for death was 0.90 for the enalapril group
      compared with the placebo group (95% CI 0.84-0.95, generalised Wilcoxon
      p=0.0003). Enalapril extended median survival by 9.4 months in the combined
      trials (95% CI 2.8-16.5, p=0.004). INTERPRETATION: Treatment with enalapril for 3
      4 years led to a sustained improvement in survival beyond the original trial
      period in patients with left ventricular systolic dysfunction, with an important
      increase in life expectancy.

PMID- 12788570
TI  - Computed tomographic scan of massive cerebral air embolism.

PMID- 12788571
TI  - Assessment of efficacy of varicocele repair for male subfertility: a systematic
      review.
AB  - BACKGROUND: Varicocele repair is a widely used treatment for subfertility. Our
      aim was to identify and combine the results from randomised controlled trials
      published to ascertain whether the pregnancy rates after varicocele repair are
      higher than those with no treatment. METHODS: We did a systematic review of seven
      studies identified by searching Medline and a register of controlled trials. We
      also searched the contents of specialist journals and the annual meeting
      programmes of relevant societies by hand. Inclusion criteria were treatment of
      varicocele in subfertile couples, random allocation to treatment and control
      groups, and pregnancy or livebirth rates as an outcome measure. We pooled data by
      use of fixed and random effects models. FINDINGS: None of seven eligible studies
      published between 1979 and 2002 described a strategy for concealment of the
      allocation sequence. There were 61 pregnancies among 281 treated couples and 50
      pregnancies among 259 controls. The overall relative benefit of treatment was
      1.01 (95% CI 0.73-1.40) by the fixed effects model and 1.04 (0.62-1.75) by the
      random effects model. The overall risk difference was 0.2% (-7 to 7) and 3% (-7
      to 14), respectively. In subgroup analyses, varicocele treatment was not
      effective in trials restricted to male subfertility with clinical varicocele, or
      in those that included men with subclinical varicocele or normal semen analysis.
      However, this systematic review, done with a meta-analytical method, might have
      had insufficient power to detect small effects because of the small number of
      patients in some subgroups. INTERPRETATION: Varicocele repair does not seem to be
      an effective treatment for male or unexplained subfertility.

PMID- 12788572
TI  - Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers
      in infants in Tanzania: a randomised placebo-controlled trial.
AB  - BACKGROUND: Malaria is a major cause of infant morbidity and mortality in sub
      Saharan Africa, and is often complicated by severe anaemia. Resistance of
      Plasmodium falciparum to most affordable antimalarial drugs is an impediment to
      intermittent chemotherapy. We investigated the effect of presumptive intermittent
      treatment with amodiaquine and daily iron supplementation in infants on malarial
      fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely
      resistant to chloroquine and sulfadoxine/ pyrimethamine. METHODS: 291 infants
      aged 12-16 weeks who attended three clinics were randomised to receive
      amodiaquine, iron supplementation, amodiaquine plus iron supplementation, or
      placebo. Over 6 months, we gave amodiaquine three times with intervals of 60
      days; oral iron supplementation was given daily. Malarial fevers and anaemia were
      monitored at bimonthly treatment visits and by self-reporting to health centres.
      FINDINGS: The protective efficacy of intermittent amodiaquine treatment in
      prevention of malarial fevers and anaemia was 64.7% (95% CI, 42.4-77.2) and 67.0%
      (95% CI, 34.5-83.4), respectively. Protective efficacy was similar in the group
      receiving amodiaquine plus iron supplementation. Infants receiving iron
      supplementation only were partly protected against anaemia (protective efficacy
      59.8%; 95% CI, 23.4-78.9), but not against malarial fevers. 4 months' follow-up
      did not show rebound morbidity. We noted no haematological or clinical adverse
      effects. INTERPRETATION: Presumptive intermittent treatment for malaria with
      amodiaquine reduced malarial fevers and anaemia in infants, in an area with high
      resistance to other antimalarials. Intermittent treatment strategies for malaria
      in highly endemic areas could be of great benefit to public health.

PMID- 12788573
TI  - Effect of a diabetic environment in utero on predisposition to type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is affected by genetics and environmental factors. We
      aimed to assess the effect of an in-utero diabetic environment independently of
      the genetic background for type 2 diabetes. METHODS: We measured insulin
      sensitivity and insulin secretion in response to oral and intravenous glucose in
      15 non-diabetic adult offspring of mothers with type 1 diabetes (exposed
      participants) and 16 offspring of type 1 diabetic fathers (controls). No
      participants had type 1 diabetes-associated autoantibodies. We also measured
      pancreatic polypeptide, a marker of parasympathetic drive to the pancreas.
      FINDINGS: There was no difference between the groups with respect to percent body
      fat and insulin sensitivity. Five of the 15 exposed participants, but none of the
      controls had impaired glucose tolerance (p=0.02). Early insulin secretion after
      an oral glucose tolerance test was lower in exposed participants than in
      controls: 8.6 IU/mmol (SD 5.4) in exposed participants with impaired glucose
      tolerance, 14.2 IU/mmol (6.5) in those with normal glucose tolerance and 17.7
      IU/mmol (10.9) in controls (p=0.04). Mean insulin secretion rate during glucose
      infusion study was 4.7 pmol/kg per min (3.6) in people with impaired glucose
      tolerance, 5.5 pmol/kg per min (4.5) in exposed participants with normal glucose
      tolerance and 7.5 pmol/kg per min (6.1) in controls (p<0.0001). The area under
      the curve of pancreatic polypeptide 120 min after oral glucose ingestion was 1007
      (429) in people with impaired glucose tolerance, 2829 (1701) in those with normal
      glucose tolerance, and 3224 (1352) in controls (p=0.04). INTERPRETATION: Exposure
      to a diabetic environment in utero is associated with increased occurrence of
      impaired glucose tolerance and a defective insulin secretory response in adult
      offspring, independent of genetic predisposition to type 2 diabetes. This insulin
      secretory defect could be related to low parasympathetic tone. Epidemiological
      studies are needed to confirm our observations before therapeutic strategies can
      be devised.

PMID- 12788574
TI  - Headache and confusion: the dangers of a raw snail supper.

PMID- 12788575
TI  - Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002.
AB  - The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP)
      monitors trends in antimicrobial resistance in consecutive gonococcal isolates
      from 26 genitourinary medicine clinics in England and Wales. In 2002, 2204
      gonococcal isolates were tested, and the overall prevalence of ciprofloxacin
      resistance (minimum inhibitory concentration > or =1 mg/L) was 9.8%, compared
      with 3.1% in 2001 and 2.1% in 2000. Between 2001 and 2002, prevalence of
      ciprofloxacin resistance increased two to three-fold, irrespective of recent
      sexual contact overseas, sex, or residence within or outside of London. These
      findings suggest that national and local treatment guidelines need to be reviewed
      urgently.

PMID- 12788576
TI  - Probiotics and prevention of atopic disease: 4-year follow-up of a randomised
      placebo-controlled trial.
AB  - Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG (ATCC
      53103), reduces incidence of atopic eczema in at-risk children during the first 2
      years of life (infancy). We have therefore assessed persistence of the potential
      to prevent atopic eczema at 4 years. Atopic disease was diagnosed on the basis of
      a questionnaire and a clinical examination. 14 of 53 children receiving
      lactobacillus had developed atopic eczema, compared with 25 of 54 receiving
      placebo (relative risk 0.57, 95% CI 0.33-0.97). Skin prick test reactivity was
      the same in both groups: ten of 50 children previously given lactobacillus
      compared with nine of 50 given placebo tested positive. Our results suggest that
      the preventive effect of lactobacillus GG on atopic eczema extends beyond
      infancy.

PMID- 12788577
TI  - Association between tuberculosis and a polymorphic NFkappaB binding site in the
      interferon gamma gene.
AB  - Interferon gamma is believed to be crucial for host defence against many
      infections. To test the hypothesis that a polymorphism in the gene for interferon
      gamma (IFNG) is associated with susceptibility to tuberculosis, we did two
      independent investigations. In a case-control study of 313 tuberculosis cases, we
      noted a significant association between a polymorphism (+874A-->T) in IFNG and
      tuberculosis in a South African population (p=0.0055). This finding was
      replicated in a family-based study, in which the transmission disequilibrium test
      was used in 131 families (p=0.005). The transcription factor NFkappaB binds
      preferentially to the +874T allele, which is over-represented in controls. This
      preferential binding suggests that genetically determined variability in
      interferon gamma and expression might be important for the development of
      tuberculosis.

PMID- 12788579
TI  - End of an era as Lee confirmed to succeed Brundtland.

PMID- 12788578
TI  - Sparks fly over patents and vital drugs at world health assembly.

PMID- 12788582
TI  - Much needed aid helps Pakistan step up polio fight.

PMID- 12788583
TI  - SARS back in Canada.

PMID- 12788585
TI  - Asia grapples with spreading amphetamine abuse.

PMID- 12788586
TI  - Uganda's state-owned drug firm pressured to drop drug deal.

PMID- 12788587
TI  - Adrenal insufficiency.
AB  - Adrenal insufficiency is caused by either primary adrenal failure (mostly due to
      autoimmune adrenalitis) or by hypothalamic-pituitary impairment of the
      corticotropic axis (predominantly due to pituitary disease). It is a rare
      disease, but is life threatening when overlooked. Main presenting symptoms such
      as fatigue, anorexia, and weight loss are non-specific, thus diagnosis is often
      delayed. The diagnostic work-up is well established but some pitfalls remain,
      particularly in the identification of secondary adrenal insufficiency. Despite
      optimised life-saving glucocorticoid-replacement and mineralocorticoid
      replacement therapy, health-related quality of life in adrenal insufficiency is
      more severely impaired than previously thought. Dehydroepiandrosterone
      replacement therapy has been introduced that could help to restore quality of
      life. Monitoring of glucocorticoid-replacement quality is hampered by lack of
      objective methods of assessment, and is therefore largely based on clinical
      grounds. Thus, long-term management of patients with adrenal insufficiency
      remains a challenge, requiring an experienced specialist. However, all doctors
      should know how to diagnose and manage suspected acute adrenal failure.

PMID- 12788588
TI  - Descriptive review of the evidence for the use of metformin in polycystic ovary
      syndrome.
AB  - Use of metformin in polycystic ovary syndrome (PCOS) is becoming increasingly
      accepted and widespread, but clinical practice is ahead of the evidence. Although
      a wide range of benefits in metabolic, reproductive, and clinical measures have
      been reported from non-randomised trials with metformin, close inspection of
      results from the adequately controlled studies shows that the benefits are
      modest. Our aim in this descriptive review is not to define practice guidelines
      but to improve clinicians' knowledge of the available published clinical
      evidence, concentrating on the few randomised controlled trials. We also
      highlight other issues, including hirsutism, acne, pregnancy, and neonatal
      outcome, that require more attention before clinical recommendations for the use
      of metformin in PCOS can be formalised. The potentially greater benefits
      achievable by lifestyle changes alone are also emphasised. We hope that the
      review will lead to more judicious use of metformin in PCOS and a more structured
      approach to research.

PMID- 12788589
TI  - Meningococcal conjugate vaccine for Africa: a model for development of new
      vaccines for the poorest countries.

PMID- 12788590
TI  - SARS: screening, disease associations, and response.

PMID- 12788591
TI  - Sodium iodide symporter: a new strategy to target cancer?

PMID- 12788592
TI  - SARS: screening, disease associations, and response.

PMID- 12788593
TI  - SARS: screening, disease associations, and response.

PMID- 12788594
TI  - UK National Health Service R&D funding--a bureaucratic nightmare.

PMID- 12788595
TI  - Maintenance buprenorphine for opioid users.

PMID- 12788596
TI  - Maintenance buprenorphine for opioid users.

PMID- 12788598
TI  - In search of genetic precision.

PMID- 12788599
TI  - Palestine, Israel, and Araz.

PMID- 12788600
TI  - In search of genetic precision.

PMID- 12788602
TI  - HIV-1 in eastern Europe.

PMID- 12788603
TI  - Medical innovators: time to show some respect.

PMID- 12788604
TI  - Medical inovators: time to show some respect.

PMID- 12788605
TI  - Anastrozole as a preventive agent in breast cancer.

PMID- 12788606
TI  - Hashimoto's enchephalopathy.

PMID- 12788608
TI  - Hashimoto's encephalopathy.

PMID- 12788609
TI  - Hashimoto's enchephalopathy.

PMID- 12788610
TI  - Risk factors for anorexia nervosa.

PMID- 12788611
TI  - Risk factors for anorexia nervosa.

PMID- 12788613
TI  - Asthma mistaken for chronic obstructive pulmonary disease.

PMID- 12788614
TI  - Hormonal contraception and cervical cancer.

PMID- 12788615
TI  - Reporting on the eye and other surgical organ systems.

PMID- 12788617
TI  - Whipple's disease, genomics, and drug therapy.

PMID- 12788618
TI  - Non-vegetarian anaesthesia.

PMID- 12788619
TI  - Phil Whitaker.

PMID- 12788624
TI  - Developing baculovirus-insect cell expression systems for humanized recombinant
      glycoprotein production.
AB  - The baculovirus-insect cell expression system is widely used to produce
      recombinant glycoproteins for many different biomedical applications. However,
      due to the fundamental nature of insect glycoprotein processing pathways, this
      system is typically unable to produce recombinant mammalian glycoproteins with
      authentic oligosaccharide side chains. This minireview summarizes our current
      understanding of insect protein glycosylation pathways and our recent efforts to
      address this problem. These efforts have yielded new insect cell lines and
      baculoviral vectors that can produce recombinant glycoproteins with humanized
      oligosaccharide side chains.

PMID- 12788625
TI  - Replication and transmission of influenza viruses in Japanese quail.
AB  - Quail have emerged as a potential intermediate host in the spread of avian
      influenza A viruses in poultry in Hong Kong. To better understand this possible
      role, we tested the replication and transmission in quail of influenza A viruses
      of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes.
      Influenza A viruses replicated predominantly in the respiratory tract.
      Transmission experiments suggested that perpetuation of avian influenza viruses
      in quail requires adaptation. Swine influenza viruses were isolated from the
      respiratory tract of quail at low levels. There was no evidence of human
      influenza A or B virus replication. Interestingly, a human-avian recombinant
      containing the surface glycoprotein genes of a quail virus and the internal genes
      of a human virus replicated and transmitted readily in quail; therefore, quail
      could function as amplifiers of influenza virus reassortants that have the
      potential to infect humans and/or other mammalian species.

PMID- 12788626
TI  - Human immunodeficiency virus type 1 capsid protein is a substrate of the
      retroviral proteinase while integrase is resistant toward proteolysis.
AB  - The capsid protein of human immunodeficiency virus type 1 was observed to undergo
      proteolytic cleavage in vitro when viral lysate was incubated in the presence of
      dithiothreitol at acidic pH. Purified HIV-1 capsid protein was also found to be a
      substrate of the viral proteinase in a pH-dependent manner; acidic pH (<7) was
      necessary for cleavage, and decreasing the pH toward 4 increased the degree of
      processing. Based on N-terminal sequencing of the cleavage products, the capsid
      protein was found to be cleaved at two sites, between residues 77 and 78 as well
      as between residues 189 and 190. Oligopeptides representing these cleavage sites
      were also cleaved at the expected peptide bonds. The presence of cyclophilin A
      decreased the degree of capsid protein processing. Unlike the capsid protein,
      integrase was found to be resistant toward proteolysis in good agreement with its
      presence in the preintegration complex.

PMID- 12788627
TI  - Analysis of the herpes simplex virus type 1 UL6 gene in patients with stromal
      keratitis.
AB  - Recent work suggests that herpes simplex virus (HSV) stromal keratitis in the
      mouse is caused by autoreactive T lymphocytes triggered by a 16 amino acid region
      of the HSV UL6 protein (aa299-314), Science 279, 1344-1347). In the present study
      we sought to determine whether genetic variation of this presumed autoreactive
      UL6 epitope is responsible for different pathogenic patterns of human HSV
      keratitis. To accomplish this, we sequenced the HSV UL6 gene from ocular isolates
      of 10 patients with necrotizing stromal keratitis, 7 patients with recurrent
      epithelial keratitis, and 8 patients with other forms of HSV keratitis. The
      sequences obtained predicted identical UL6(299-314) epitopes for all 25 viral
      isolates. Furthermore, the upstream sequence of all isolates was free of
      insertions, deletions, and stop codons. We conclude that different pathogenic
      patterns of human HSV keratitis occur independent of genetic variation of the HSV
      UL6 (299-314) epitope.

PMID- 12788628
TI  - Localization of influenza virus proteins to nuclear dot 10 structures in
      influenza virus-infected cells.
AB  - We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that
      express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was
      incorporated into virions produced by influenza virus infected MDCK cells
      expressing the fusion protein indicating that the fusion protein is at least
      partially functional. Following infection of either HeLa or MDCK cells with
      influenza A virus (but not influenza B virus), GFP-M1 redistributes from its
      cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence
      revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The
      colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was
      confirmed by immunofluorescence following in situ isolation of ND10. These
      findings demonstrate a previously unappreciated involvement of influenza virus
      with ND10, a structure involved in cellular responses to immune cytokines as well
      as the replication of a rapidly increasing list of viruses.

PMID- 12788629
TI  - Comparative analysis of the transcriptional patterns of pathogenic and
      nonpathogenic porcine circoviruses.
AB  - The RNAs of porcine circovirus type 1 (PCV1) synthesized in PK15 cells were
      characterized. A total of 12 RNAs were detected. They include the viral capsid
      protein RNA (CR), a cluster of eight Rep-associated RNAs (designated Rep, Rep',
      Rep3a, Rep3b, Rep3c-1, Rep3c-2, Rep3c-3, and Rep3c-4), and three NS-associated
      RNAs (designated NS462, NS642, and NS0). Members of the Rep-associated RNA
      cluster all share common 5'- and 3'-nucleotide sequences and they share common 3'
      nucleotide sequence with the NS-associated RNAs. Rep, capable of coding for the
      full-length replication-associated protein, appears to be the primary transcript
      that gives rise to the other seven Rep-associated RNAs by alternate splicing.
      NS462, NS642, and NS0 appear to have been transcribed from three different
      promoters present inside ORF1, independent from the Rep promoter. Based on
      sequence alignment analysis, both the nonpathogenic PCV1 and the pathogenic
      porcine circovirus type 2 (PCV2) (with nine RNAs: Rep, Rep', Rep3a, Rep3b, Rep3c,
      NS515, NS672, and NS0) utilize comparable genetic elements similarly located
      along the genome for viral gene expression. The Rep, Rep', Rep3a, Rep3b, and NS0
      of PCV1 and PCV2 are considered equivalent entities in their respective systems.
      However, quantitative and qualitative differences (splice junction variation)
      were observed among the Rep3c- and NS-associated RNAs. This work provides a
      general framework and genetic basis to investigate the biologic properties (and
      differences) of PCV1 and PCV2.

PMID- 12788630
TI  - Cowpea mosaic virus-based chimaeras. Effects of inserted peptides on the
      phenotype, host range, and transmissibility of the modified viruses.
AB  - Expression of foreign peptides on the surface of cowpea mosaic virus particles
      leads to the creation of chimaeras with a variety of phenotypes and yields. Two
      factors were shown to be particularly significant in determining the properties
      of a given chimaera: the length of the inserted sequence and its isoelectric
      point. The deleterious effect of high isoelectric point on the ability of
      chimeras to produce a systemic infection occurs irrespective of the site of
      insertion of the peptide. Ultrastructural analysis of tissue infected with
      chimaeras with different phenotypes showed that all produced particles with a
      tendency to aggregate, irrespective of the size or isoelectric point of the
      insert. Host range and transmission studies revealed that the expression of a
      foreign peptide did not (1) alter the virus host range, (2) increase the rate of
      transmission by beetles or through seed, or (3) change the insect vector
      specificity. These findings have implications for both the utility and the
      biosafety of Cowpea mosaic virus-based chimaeras.

PMID- 12788631
TI  - Genetic analyses of putative conformation switching and cross-species inhibitory
      domains in Microviridae external scaffolding proteins.
AB  - Putative conformational switching and inhibitory regions in the Microviridae
      external scaffolding protein were investigated. Substitutions for glycine 61,
      hypothesized to promote a postdimerization conformational switch, have dominant
      lethal phenotypes. In previous studies, chimeric alpha3/phiX174 proteins for
      structures alpha-helix 1 and loop 6/alpha-helix 7 inhibited phiX174 morphogenesis
      when expressed from high copy number plasmids. To determine if inhibition was due
      to overexpression, chimeric genes were constructed into the phiX174 genome. In
      coinfections with wild-type, protein ratios would be 1:1. The helix 1 chimera has
      a recessive lethal phenotype; thus, overexpression confers inhibition. In single
      infections, the mutant cannot form procapsids, suggesting that helix 1 mediates
      the initial recognition of structural proteins. The lethal chimeric helix 7
      protein has a dominant phenotype. Alone, the mutant forms defective procapsids,
      suggesting a later morphogenetic defect. The results of second-site genetic
      analyses indicate that the capsid-external scaffolding protein interface is
      larger than revealed in the crystal structure.

PMID- 12788632
TI  - Lytic switch protein (ORF50) response element in the Kaposi's sarcoma-associated
      herpesvirus K8 promoter is located within but does not require a palindromic
      structure.
AB  - Kaposi's sarcoma-associated virus (KSHV) ORF50 protein induces lytic replication
      and activates the K8 promoter. We show that ORF50-induced and tetradecanoyl
      phorbol acetate (TPA) induced K8 transcripts initiated from the same start site.
      A newly identified palindrome (PAL2), containing a 12-bp response region required
      for ORF50-induced activation in lymphoid cells, was identified in the K8
      promoter. Specific DNA binding of bacterially expressed ORF50 was not seen with
      the K8 promoter despite specific binding to the PAN promoter. The new palindrome
      shared homology with a previously described ORF50 response element (50RE(K8) and
      50RE(57)). We demonstrate that the new 50RE(K8) (50RE(K8-PAL2)) is not the
      palindrome per se. Instead, the response element is buried within the right arm
      of the palindrome. We propose that the complexity of the K8 response elements
      reflects the complexity of mechanisms used by ORF50 during viral reactivation.

PMID- 12788633
TI  - Mapping of determinants required for the function of the HIV-1 env nuclear
      retention sequence.
AB  - Control of HIV-1 RNA processing and transport are critical to the successful
      replication of the virus. In previous work, we identified a region within the HIV
      1 env that is involved in mediating nuclear retention of unspliced viral RNA. To
      define this sequence further and identify elements required for function,
      deletion mutagenesis was carried out. Progressive 5' and 3' deletions map the
      nuclear retention sequence (NRS) within the intron between nts 8281 and 8381.
      While deletion of sequences comprising the 3'ss had no effect, removal of the
      5'ss resulted in cytoplasmic accumulation of unspliced RNA. Sequence analysis
      determined that the region corresponding to the NRS is highly conserved among HIV
      1 strains. To evaluate whether this NRS interacts with cellular factors, RNA
      electrophoretic mobility shift assays (REMSA) were performed. We show that the
      NRS specifically interacts with cellular factors present in HeLa nuclear
      extracts, and, by UV crosslinking, correlates with the binding of a 49-kDa
      protein. Immunoprecipitation of the UV crosslinked products determined that this
      49-kDa protein corresponds to hnRNP C.

PMID- 12788634
TI  - The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen
      maturation in human foreskin keratinocytes treated with interferon-gamma.
AB  - Major histocompatibility complex (MHC) class II antigens are expressed on human
      foreskin keratinocytes (HFKs) following exposure to interferon gamma. The
      expression of MHC class II proteins on the cell surface may allow keratinocytes
      to function as antigen-presenting cells and induce a subsequent immune response
      to virus infection. Invariant chain (Ii) is a chaperone protein which plays an
      important role in the maturation of MHC class II molecules. The sequential
      degradation of Ii within acidic endocytic compartments is a key process required
      for the successful loading of antigenic peptide onto MHC class II molecules.
      Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late
      endosomes in HFKs, the E5 protein may be able to affect proper peptide loading
      onto the MHC class II molecule. To test this hypothesis, HFKs were infected with
      either control virus or a recombinant virus expressing HPV16 E5 and the infected
      cells were subsequently treated with interferon-gamma. ELISAs revealed a decrease
      of MHC class II expression on the surface of E5-expressing cells compared with
      control virus-infected cells after interferon treatment. Western blot analysis
      showed that, in cells treated with interferon gamma, E5 could prevent the
      breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC
      class II dimers, correlating with diminished surface MHC class II expression.
      These data suggest that HPV16 E5 may be able to decrease immune recognition of
      infected keratinocytes via disruption of MHC class II protein function.

PMID- 12788635
TI  - Effect of selected mutations in the C-terminal region of the vaccinia virus
      nucleoside triphosphate phosphohydrolase I on binding to the H4L subunit of the
      viral RNA polymerase and early gene transcription termination in vitro.
AB  - Vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH I) is an essential
      early gene transcription termination factor. The C-terminal end of NPH I binds to
      the N-terminal end of the H4L subunit (RAP94) of the virion RNA polymerase. This
      interaction is required for transcription termination and transcript release. To
      refine our understanding of the specific amino acids in the C-terminal end of NPH
      I involved in binding to H4L, and to develop a collection of mutations exhibiting
      various degrees of activity to be employed in in vivo studies, we prepared a set
      of short deletions, and clustered substitutions of charged amino acids to
      alanine, or bulky hydrophobic amino acids to alanine mutations. These NPH I
      mutant proteins were expressed, purified, and tested for ATPase activity, binding
      to H4L, and transcription termination activity. Most mutations in amino acids 609
      to 631 exhibited reduced activity. Deletion of the terminal five amino acids (627
      631), or substitution of Y(629) with alanine or glutamic acid, dramatically
      reduced NPH I mediated transcription termination. Deletion of the terminal
      F(631), or substitution of F(631) with alanine, reduced binding to H4L and
      eliminated termination activity. These observations demonstrate that the terminal
      five amino acids directly participate in binding to RNA polymerase and in early
      gene transcription termination.

PMID- 12788636
TI  - Enhancement of RNA synthesis by promoter duplication in tombusviruses.
AB  - Replication of tombusviruses, small plus-strand RNA viruses of plants, is
      regulated by cis-acting elements present in the viral RNA. The role of cis-acting
      elements can be studied in vitro by using a partially purified RNA-dependent RNA
      polymerase (RdRp) preparation obtained from tombusvirus-infected plants, Virology
      276, 279- 288). Here, we demonstrate that the minus-strand RNA of tombusviruses
      contains, in addition to the 3'-terminal minimal plus-strand initiation promoter,
      a second cis-acting element, termed the promoter proximal enhancer (PPE). The PPE
      element enhanced RNA synthesis by almost threefold from the adjacent minimal
      promoter in the in vitro assay. The sequence of the PPE element is 70% similar to
      the minimal promoter, suggesting that sequence duplication of the minimal
      promoter may have been the mechanism leading to the generation of the PPE.
      Consistent with this proposal, replacement of the PPE element with the minimal
      promoter, which resulted in a perfectly duplicated promoter region, preserved its
      enhancer-like function. In contrast, mutagenesis of the PPE element or its
      replacement with an artificial G/C-rich sequence abolished its stimulative effect
      on initiation of RNA synthesis in vitro. In vivo experiments are also consistent
      with the role of the PPE element in enhancement of tombusvirus replication.
      Sequence comparison of several tombusviruses and related carmoviruses further
      supports the finding that duplication of minimal promoter sequences may have been
      an important mechanism during the evolution of cis-acting elements in
      tombusviruses and related RNA viruses.

PMID- 12788637
TI  - Functional interaction between the N- and C-terminal domains of murine leukemia
      virus surface envelope protein.
AB  - A series of murine leukemia viruses (MuLVs) with chimeric envelope proteins (Env)
      was generated to map functional interactions between the N- and the C-terminal
      domains of surface proteins (SU). All these chimeras have the 4070A amphotropic
      receptor-binding region flanked by various lengths of Moloney ecotropic N- and C
      terminal Env. A charged residue, E49 (E16 on the mature protein), was identified
      at the N-terminals of Moloney MuLV SU that is important for the interaction with
      the C-terminal domain of the SU. The region that interacts with E49 was localized
      between junction 4 (R265 of M-MuLV Env) and junction 6 (L374 of M-MuLV Env) of
      SU. Sequencing the viable chimeric Env virus populations identified residues
      within the SU protein that improved the replication kinetics of the input
      chimeric Env viruses. Mutations in the C-domain of SU (G387E/R, L435I, L442P)
      were found to improve chimera IV4, which displayed a delayed onset of
      replication. The replication of AE6, containing a chimeric junction in the SU C
      terminus, was improved by mutations in the N-domain (N40H, E80K), the proline
      rich region (Q252R), or the transmembrane protein (L538N). Altogether, these
      observations provide insights into the structural elements required for Env
      function.

PMID- 12788638
TI  - Differential activation of Tat variants in mitogen-stimulated cells: implications
      for HIV-1 postintegration latency.
AB  - Like other HIV-1 (human immunodeficiency virus type 1) proteins, Tat undergoes
      rapid mutation and occurs in numerous sequence variants in nature. Virus isolated
      from patients often has defects in Tat that lower its activity. The levels of P
      TEFb, an essential cellular cofactor for Tat, are elevated by T-cell activation.
      To test the hypothesis that stimulation of P-TEFb levels might compensate for
      attenuation of Tat activity, we generated Tat constructs with a range of
      transactivation function. Transactivation by the Tat mutants correlated with
      their ability to bind to P-TEFb in vitro. Treatment of U937 cells with the
      phorbol ester PMA (phorbol myristate acetate) induced P-TEFb and stimulated Tat
      transactivation for alleles with basal transcription activity above a threshold
      (>5% compared to wild-type). Highly active alleles (>66% of wild-type) were
      stimulated to a lesser extent than those with activity in the intermediate range.
      Thus, attenuation of Tat function, in concert with low levels of P-TEFb activity,
      could serve to keep the virus in a latent state in quiescent cells yet permit
      viral replication after cell activation.

PMID- 12788639
TI  - The mature reverse transcriptase molecules in virions of mouse mammary tumor
      virus possess protease-derived sequences.
AB  - Our efforts to express in bacteria the enzymatically active reverse transcriptase
      (RT) of mouse mammary tumor virus (MMTV) have shown that the RT is active only
      after adding 27 amino acid residues, which are derived from the end of the pro
      gene, to the amino-terminus of the RT (Biochem, J. (1998) 329, 579-587). In the
      present study we have tested whether the mature RT found in virions is also fused
      to protease-derived sequences. To this end, we have analyzed the RT molecules in
      virions of MMTV by using two antisera directed against peptides, derived from
      either the carboxyl-terminus of MMTV protease or the middle of MMTV RT. The data
      suggest that the mature RT, located in virions, contains at its amino-terminus
      sequences from the carboxyl-terminus of the protease protein. This finding
      supports previous suggestions that MMTV RT is a transframe protein (derived from
      both pro and pol reading frames of MMTV) and that amino acid residues located at
      the carboxyl-terminus of the protease have a dual usage as integral parts of both
      the protease and the RT enzymes.

PMID- 12788640
TI  - Carboxy-fluorescein diacetate, succinimidyl ester labeled papillomavirus virus
      like particles fluoresce after internalization and interact with heparan sulfate
      for binding and entry.
AB  - Human papillomaviruses (HPVs) infect epithelial cells and are associated with
      genital carcinoma. Most epithelial cell lines express cell-surface
      glycosaminoglycans (GAGs) usually found attached to the protein core of
      proteoglycans. Our aim was to study how GAGs influenced HPV entry. Using a human
      keratinocyte cell line (HaCaT), preincubation of HPV virus-like particles (VLPs)
      with GAGs showed a dose-dependent inhibition of binding. The IC(50) (50%
      inhibition) was only 0.5 microg/ml for heparin, 1 microg/ml for dextran sulfate,
      and 5-10 microg/ml for heparan sulfate from mucosal origin. Mutated chinese
      hamster ovary (CHO) cell lines lacking heparan sulfate or all GAGs were unable to
      bind HPV VLPs. Here we also report a method to study internalization by using
      VLPs labeled with carboxy-fluorescein diacetate, succinimidyl ester, a
      fluorochrome that is only activated after cell entry. Pretreatment of labeled HPV
      VLPs with heparin inhibited uptake, suggesting a primary interaction between HPV
      and cell-surface heparan sulfate.

PMID- 12788641
TI  - The archetype enhancer of simian virus 40 DNA is duplicated during virus growth
      in human cells and rhesus monkey kidney cells but not in green monkey kidney
      cells.
AB  - Archetype SV40, obtained directly from its natural host, is characterized by a
      single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost
      invariably exhibits partial or complete duplication of the enhancer region. This
      distinction has been considered important in studies of human tumor material,
      since SV40-associated tumor isolates have been described having a single enhancer
      region, suggesting natural infection as opposed to possible contamination by
      laboratory strains of virus. However, the behavior of archetypal SV40 in cultured
      cells has never been methodically studied. In this study we reengineered
      nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this
      reengineered archetypal DNA to transfect a number of simian and human cell lines.
      SV40 DNA recovered from these cells was analyzed by restriction endonuclease
      analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in
      green monkey TC-7 or BSC-1 kidney cells remained without enhancer region
      duplication even after extensive serial virus passage. Archetype SV40 grown in
      all but one of the rhesus or human cell lines initially appeared exclusively
      archetypal. However, when virus from these cell types was transferred to green
      monkey cells, variants with partial enhancer duplication appeared after as little
      as a single passage. These findings suggest (1) that virus with a single 72-bp
      enhancer may persist in cultured cells of simian and human origin; (2) that
      variants with partially duplicated enhancer regions may arise within cell lines
      in quantities below limits of detection; (3) that these variants may enjoy a
      selective advantage in cell types other than those from which they arose (e.g.,
      green monkey kidney cells); and (4) that certain cell lines may support a
      selective growth advantage for the variants without supporting their formation.
      Our data indicate that enhancer duplication may also occur in human as well as
      rhesus kidney cells. Thus, detection of enhancer region duplication may not, a
      priori, indicate laboratory contamination, nor does detection of a single 72-bp
      enhancer exclude the possibility that contamination may have occurred. These
      findings may be of relevance to studies attempting to detect SV40 DNA in human
      tumors or other clinical specimens.

PMID- 12788642
TI  - The molecular basis of the antigenic cross-reactivity between measles and cowpea
      mosaic viruses.
AB  - Two nonrelated viruses, cowpea mosaic virus (wtCPMV) and measles virus (MV), were
      found to induce cross-reactive antibodies. The nature of this cross-reactivity
      was studied and results are presented here demonstrating that antiserum raised
      against wtCPMV reacted with peptide from the fusion (F) protein of MV.
      Furthermore, the F protein of MV was shown to share an identical conformational B
      cell epitope with the small subunit of CPMV coat protein. Passive transfer of
      anti-wtCPMV antibodies into BALB/c mice conferred partial protection against
      measles virus induced encephalitis. The results are discussed in the context of
      cross-protection.

PMID- 12788644
TI  - SARS: fear of global pandemic.

PMID- 12788643
TI  - Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via
      distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to
      promote transactivation by CREB.
AB  - Nef and Vpr are lentiviral accessory proteins that have been implicated in
      regulation of cellular gene expression. We noticed that Vpr can potentiate Nef
      induced activation of nuclear factor of activated T cells (NFAT)-dependent
      transcription. Unlike Nef, which stimulated calcium signaling to activate NFAT,
      Vpr functioned farther downstream. Similar to the positive effects of Vpr on most
      of the transcriptional test systems that we used, potentiation of NFAT-directed
      gene expression was relatively modest in magnitude (two- to threefold) and
      depended on the cell cycle-arresting capacity of Vpr. By contrast, we found that
      Vpr could cause more than fivefold upregulation of cyclic AMP response element
      (CRE)-directed transcription via a mechanism that did not require Vpr-induced
      G2/M arrest. This effect, however, was only evident under suboptimal conditions
      known to lead to serine phosphorylation of the CRE binding factor (CREB) but not
      to CREB-dependent gene expression. This suggested that Vpr may act by stabilizing
      interactions with CREB and its transcriptional cofactor CREB binding protein
      (CBP). Indeed, this effect could be blocked by cotransfection of the adenoviral
      CBP inhibitor E1A. These results provide additional evidence for cell cycle
      independent regulation of gene expression by Vpr and implicate CREB as a
      potentially important target for Vpr action in HIV-infected host cells.

PMID- 12788645
TI  - A novel TAT-mitochondrial signal sequence fusion protein is processed, stays in
      mitochondria, and crosses the placenta.
AB  - Mutations in nuclear and mitochondrial genomes can lead to defects in
      mitochondrial function. To date, repair of these defects with exogenous proteins
      or gene transfer has been difficult with either viral or nonviral vectors. We
      hypothesized that TAT fusion proteins would cross both mitochondrial membranes
      and that incorporation of a mitochondrial signal sequence into a TAT fusion
      protein would allow processing and localization of exogenous proteins in
      mitochondria. A TAT-mitochondrial malate dehydrogenase signal sequence (mMDH)
      enhanced green fluorescent protein (eGFP) fusion protein was constructed. TAT
      mMDH-eGFP allowed rapid transduction and localization of fusion protein into
      mitochondria of multiple cell types. In contrast, TAT-GFP, without a
      mitochondrial signal sequence, rapidly transduced into cells and mitochondria,
      displayed pseudo-first-order kinetics, but did not remain there. Mice injected 5
      days prior with TAT-mMDH-eGFP had detectable eGFP activity in multiple tissue
      types. Western blotting of cytosolic and mitochondrial fractions isolated from
      their livers confirmed eGFP localization to mitochondria and that the mMDH
      transit peptide was recognized and processed. Furthermore, TAT-mMDH-eGFP fusion
      protein injected into pregnant mice crossed the placenta and was detectable in
      both the fetus and the newborn pups. TAT fusion proteins containing a
      mitochondrial signal sequence are a viable method to localize proteins to
      mitochondria.

PMID- 12788646
TI  - Combined effects of docetaxel and angiostatin gene therapy in prostate tumor
      model.
AB  - The anti-tumor effects of adenovirus-delivered angiostatin (AdK3) in association
      with docetaxel (Taxotere) have been evaluated in a human-origin prostate tumor
      model. In vitro, human endothelial cells were 50- to 100-fold more sensitive to
      docetaxel than prostate cell lines (PC3, LNCaP, and DU145), and the combination
      regimen of docetaxel and AdK3 was significantly more cytotoxic for endothelial
      cells than either treatment alone. PC3 cells, which display the highest
      sensitivity to docetaxel, were then grafted onto athymic mice for an evaluation
      of the combined regimen as a therapy. The combination of a single intratumoral
      injection of AdK3 (2 x 10(9) pfu) and a single intravenous injection of docetaxel
      (15 mg/kg) was compared with the injection of AdK3 alone on preestablished mice
      bearing PC3-derived tumors with a mean tumor volume of 60 +/- 11 or 205 +/- 46
      mm3. Significant antitumoral effects were observed only in mice receiving the
      combined treatment. We showed that all PC3 tumors regressed in the AdK3-docetaxel
      combination group and that 40 to 83% totally regressed. In all cases, this
      regimen was tightly correlated with a marked decrease in intratumoral
      vascularization. Our experimental data show that attacking both endothelial and
      tumoral compartments is an efficient and logical strategy, making this bitherapy
      approach clinically promising.

PMID- 12788647
TI  - Requirement of an integrated immune response for successful neuroattenuated HSV-1
      therapy in an intracranial metastatic melanoma model.
AB  - Neuroattenuated herpes simplex virus ICP34.5 mutants slow progression of
      preformed tumors and lead to complete regression of some tumors. Although this
      was previously thought to be due to viral lysis of infected tumor cells, it is
      now understood that there is an immune component to tumor destruction. We have
      previously shown that no difference in survival is seen in lymphocyte-depleted
      mice after viral or mock therapy of syngeneic intracranial melanomas. We have
      also demonstrated the presence of a wide spectrum of immune cells following viral
      therapy, including larger percentages of CD4+ T cells and macrophages. In this
      paper, the contribution of the immune system to tumor destruction has been
      further delineated. Viral therapy of intracranial melanoma induces a tumor
      specific cytotoxic and proliferative T cell response. However, there is no
      increase following viral therapy in either serum tumor antibody levels or viral
      neutralizing antibodies. Thus specific T cell responses appear to mediate viral
      elicited prolongation in survival. These data suggest that designing new viruses
      capable of augmenting T cell responses may induce stronger tumor destruction upon
      viral therapy.

PMID- 12788648
TI  - Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex
      virus potentiates the viral antitumor effect.
AB  - Oncolytic viruses have shown considerable promise in the treatment of solid
      tumors, but their potency must be improved if their full clinical potential is to
      be realized. We inserted the gene encoding a truncated form of the gibbon ape
      leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an
      oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent
      in vitro and in vivo studies showed that expression of GALV.fus in the context of
      an oncolytic virus significantly enhances the antitumor effect of the virus.
      Furthermore, by controlling GALV.fus expression through a strict late viral
      promoter, whose activity depends on the initiation of viral DNA replication, we
      were able to express this glycoprotein in tumor cells but not in normal
      nondividing cells. It will be of interest to confirm whether functional
      expression of a strong fusogenic gene by an oncolytic herpes simplex virus
      enhances viral antitumor activity without increasing its toxicity.

PMID- 12788649
TI  - In vitro and in vivo activities of an oncolytic adenoviral vector designed to
      express GM-CSF.
AB  - Oncolytic adenoviruses are being tested as biological cancer therapeutics.
      Ar6pAE2fF (E2F vector) contains the E2F-1 promoter to regulate the expression of
      the E1a gene in cells with a disregulated retinoblastoma pathway. Ar6pAE2fmGmF
      (E2F-GM vector) includes the murine granulocyte-macrophage colony-stimulating
      factor (GM-CSF) transgene to enhance anti-tumor activity. Both vectors
      selectively killed human tumor cells in vitro. The E2F-GM vector expressed
      biologically active murine GM-CSF in vitro and GM-CSF was detected for several
      days in serum and tumor extracts following injections of established human
      xenograft tumors. In vivo, both vectors showed significant dose-dependent anti
      tumor responses. The E2F-GM vector elicited greater efficacy compared to the E2F
      vector, demonstrating that GM-CSF enhanced the anti-tumor activity, even in
      immunodeficient nude mice. Histological analysis showed that both vectors induced
      necrosis and mononuclear cell infiltration, but only the E2F-GM vector resulted
      in eosinophil infiltration. Vector replication in vivo was demonstrated. The data
      showed that intratumoral injection of a GM-CSF-armed oncolytic vector induced
      potent anti-tumor responses in xenograft tumor models, likely as the result of
      both oncolytic vector activity and the induction of GM-CSF-mediated inflammation
      and innate immunity.

PMID- 12788650
TI  - Feasibility, sensitivity, and reliability of laser-induced fluorescence imaging
      of green fluorescent protein-expressing tumors in vivo.
AB  - Whole-body imaging of green fluorescent protein (GFP) can be used to test the
      efficiency of gene carriers for in vivo transduction. The aim of the current
      study was to determine the sensitivity and the accuracy of a GFP imaging
      procedure by in vivo investigation of GFP-expressing tumor cells. An improved
      method of whole-body GFP imaging made use of a laser excitation source and band
      pass filters matched specifically to GFP and constitutive tissue fluorescence
      emission bands. Processing of the primary GFP fluorescence images acquired by the
      CCD camera subtracted background tissue autofluorescence. Our approach achieved
      100% sensitivity and specificity for in vivo detection of 10%-transfected BxPc3
      pancreatic tumor after subcutaneous grafting or orthotopical implantation in the
      pancreas of nude mice. It also detected less transfected tumors (i.e., 1 to 5%)
      but with a loss in sensitivity (50% of cases). The system was employed over a 5
      week period to monitor the persistence of GFP expression in 10%-transfected BxPc3
      tumors orthotopically implanted in the pancreas of two nude mice, allowing the
      direct visualization of tumor progression and spread. In facilitating the
      temporal-spatial follow-up of GFP expression in vivo, the optimized laser-induced
      fluorescence imaging device can support preclinical investigations of vectors for
      therapeutic gene transduction through regular, harmless, real-time monitoring of
      theirin vivo transductional efficacy and persistence.

PMID- 12788651
TI  - Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long
      term transduction of retinal pigmented epithelium in rat, dog, and nonhuman
      primate after subretinal delivery.
AB  - We previously described chimeric recombinant adeno-associated virus (rAAV)
      vectors 2/4 and 2/5 as the most efficient vectors in rat retina. We now
      characterize these two vectors carrying the CMV.gfp genome following subretinal
      injection in the Wistar rat, beagle dog, and cynomolgus macaque. Both serotypes
      displayed stable GFP expression for the duration of the experiment (6 months) in
      all three animal models. Similar to the AAV-2 serotype, AAV-2/5 transduced both
      RPE and photoreceptor cells, with higher level of transduction in photoreceptors,
      whereas rAAV-2/4 transduction was unambiguously restricted to RPE cells. This
      unique specificity found conserved among all three species makes AAV-2/4-derived
      vectors attractive for retinal diseases originating in RPE such as Leber
      congenital amaurosis (RPE65) or retinitis pigmentosa due to a mutated mertk gene.
      To provide further important preclinical data, vector shedding was monitored by
      PCR in various biological fluids for 2 months post-rAAV administration. Following
      rAAV-2/4 and -5 subretinal delivery in dogs (n = 6) and in nonhuman primates (n =
      2), vector genome was found in lacrymal and nasal fluids for up to 3-4 days and
      in the serum for up to 15-20 days. Overall, these findings will have a practical
      impact on the development of future gene therapy trials of retinal diseases.

PMID- 12788652
TI  - Optimization of transgene expression at the posttranscriptional level in neural
      cells: implications for gene therapy.
AB  - Gene delivery vectors need to fulfill several efficacy and safety criteria before
      they can be used in humans. Successful clinical application requires effective
      transgene expression with a minimum of vector-associated toxicity. We describe
      the use of posttranscriptional regulatory elements in plasmid and lentiviral
      vectors coding for luciferase. These constructs allow high-level gene expression
      in both neuronal and glial cells. Of the several elements that we tested, WPRE
      gave the highest level of expression. Further enhancements were obtained when
      WPRE was combined with sequences corresponding to the 3' or 5' untranslated
      regions (UTR) of eukaryotic mRNAs (tau 3'UTR, TH 3'UTR, and APP 5'UTR). In
      neuronal cells, WPRE and both tau 3'UTR and APP 5'UTR had an additive effect on
      expression. The combination of the three elements increased the basal level of
      expression by up to 26-fold. In glial cells, WPRE and APP 5'UTR had additive
      effects on expression, and their combination increased expression up to 10-fold.
      These results provide important information regarding the development of optimal
      CNS gene transfer vectors not only for gene therapy but also for the study of
      gene function.

PMID- 12788653
TI  - Single HSV-amplicon vector mediates drug-induced gene expression via dimerizer
      system.
AB  - A variety of viral vectors have been used to deliver genes into various tissues.
      Most have typically relied on either viral or cell-specific mammalian promoters
      to express transgenes. More recently, regulated promoter systems have been
      developed to fine-tune gene expression. Due to limited transgene capacity in most
      viral vectors, regulatory elements are typically subcloned into two separate
      vectors, which must be delivered simultaneously to a target cell. Here, we have
      cloned all the components of the rapamycin-based "dimerizer" system into the
      pantropic HSV-amplicon vector and used it to deliver and regulate red fluorescent
      protein (RFP) expression in cultured cells in a drug-dose-dependent manner.
      293T/17 cells infected at an m.o.i. of 1 transducing unit/cell and induced with
      20 nM rapamycin resulted in a 25-fold increase in RFP mRNA levels after 24 h as
      assessed by quantitative RT-PCR. However, due to a reduced ability to detect RFP
      optically, only a 5-fold induction in the number of RFP-expressing cells was
      noted by FACS analysis 48 h after infection. Further, there was at least 100-fold
      variation in the levels of RFP in individual, infected cells in the induced
      state. Gene induction in several neuronal models, including primary cell culture
      and organotypic cultures, as well as in rodent brain, was observed.

PMID- 12788654
TI  - Inhibiting AIDS in the central nervous system: gene delivery to protect neurons
      from HIV.
AB  - Gene therapy to treat primary and secondary CNS diseases, including neuro-AIDS,
      has not yet been effective. New approaches to delivering therapeutic genes to the
      central nervous system are therefore required. Recombinant SV40 vectors (rSV40)
      transduce both dividing and quiescent cells efficiently, and so we tested them
      for their ability to deliver anti-HIV-1 transgenes to terminally differentiated
      human NT2-derived neurons (NT2-N). These vectors transduced >95% of immature as
      well as mature human neurons efficiently, without detectable toxicity and without
      requiring selection. rSV40 gene delivery was stable to retinoic acid-induced
      neuronal differentiation. The rSV40 vectors used in these studies, SV(RevM10) and
      SV(AT), respectively carried the cDNAs for RevM10, a trans-dominant mutant of HIV
      1 Rev, and human alpha1-antitrypsin. As measured by HIV-1 p24 antigen assays and
      by immunostaining for gp120, NT2-N treated with these vectors strongly resisted
      challenge with different strains of HIV-1. Protection from HIV replication and
      HIV-induced cytotoxicity was conferred by SV(AT) and SV(RevM10) and remained
      constant throughout retinoic acid-induced neuronal differentiation and for the
      duration of these studies (> or =11 weeks). rSV40 transduction of human neurons
      might therefore be a practicable approach to gene delivery for the treatment of
      CNS diseases, including neuro-AIDS.

PMID- 12788655
TI  - Small interfering RNAs expressed from a Pol III promoter suppress the EWS/Fli-1
      transcript in an Ewing sarcoma cell line.
AB  - The EWS/Fli-1 fusion gene encodes an oncogenic fusion protein. The fusion is a
      product of the translocation t(11;22) (q24;q12), which is detected in 85% of
      Ewing sarcoma and primitive neuroectodermal tumor cells. Utilizing
      intracellularly expressed 21- to 23-nucleotide small interfering RNAs (siRNAs)
      targeting the EWS/Fli-1 fusion transcript in an Ewing sarcoma cell line, we
      achieved a greater than 80% reduction in the EWS/Fli-1 transcript. The reduction
      in transcript levels was accompanied by growth inhibition of an Ewing cell line.
      In addition to quantitating the reduction of the fusion transcript, we carefully
      monitored reduction of the endogenous EWS and Fli-1 mRNAs as well. One of the two
      siRNAs targeted to the fusion transcript also partially downregulated the Fli-1
      mRNA, further potentiating the growth inhibition. These results highlight both
      the power of siRNAs and the potential side reactions that need to be carefully
      monitored. In addition, these results provide the first demonstration of
      expressed siRNAs downregulating an oncogenic fusion transcript. The results and
      observations from these studies should prove useful in targeting other fusion
      transcripts characteristic of sarcomas and erythroleukemias.

PMID- 12788656
TI  - Inhibition of HIV-1 gene expression by novel DNA enzymes targeted to cleave HIV-1
      TAR RNA: potential effectiveness against all HIV-1 isolates.
AB  - Nucleic acid-based antiviral approaches have been tried against multiple HIV-1
      genes with the purpose of down-regulating its replication. A unique stem-loop
      structure called TAR is present at the 5'-end of all HIV-1 transcripts; Tat and
      other cellular proteins bind to TAR and thus govern transcription. Therefore, HIV
      1 TAR is an attractive target against which various antiviral approaches could be
      tried. We screened several DNA enzymes (Dz's) containing the 10-23 catalytic
      motif and a single Dz containing the 8-17 catalytic motif against the HIV-1 TAR
      RNA. Dz's directed against the predicted single-stranded bulge regions showed
      sequence-specific cleavage activities. One of the two Dz's, namely Dz-475, showed
      moderate cleavage activity in complete absence of Mg(2+). Addition of unrelated
      sequences at the 5'-end of the HIV-1 TAR RNA rendered it susceptible to four
      additional Dz-mediated cleavages. Both Dz's (470 and 475) showed significant
      intracellular reduction of HIV-1 gene expression. Dz-475-treated cells showed
      significant protection against T-tropic and macrophage-tropic HIV-1 challenge. Dz
      475-transfected T-lymphocytes, human PBMCs, or chronically infected cell lines
      showed marked viral resistance. Unique features of this antiviral strategy with
      respect to HIV-1 gene inhibition are discussed.

PMID- 12788657
TI  - Lentiviral vectors with two independent internal promoters transfer high-level
      expression of multiple transgenes to human hematopoietic stem-progenitor cells.
AB  - Lentiviral vectors (LVs) offer several advantages over traditional oncoretroviral
      vectors. LVs efficiently transduce slowly dividing cells, including hematopoietic
      stem-progenitor cells (HSCs), resulting in stable gene transfer and expression.
      Additionally, recently developed self-inactivating (SIN) LVs allow promoter
      specific transgene expression. For many gene transfer applications, transduction
      of more than one gene is needed. We obtained inconsistent results in our attempts
      to coexpress two transgenes linked by an internal ribosomal entry site (IRES)
      element in a single bicistronic LV transcript. In more than six bicistronic LVs
      we constructed containing a gene of interest followed by an IRES and the GFP
      reporter gene, GFP fluorescence was undetectable in transduced cells. We
      therefore investigated how to achieve consistent and efficient coexpression of
      two transgenes by LVs. In a SIN LV containing the elongation factor 1alpha
      promoter, we included a second promoter from cytomegalovirus, the
      phosphoglycerate kinase gene, or the HLA-DRalpha gene. Using a single LV
      containing two constitutive promoters, we achieved strong and sustained
      expression of both transgenes in transduced engrafting CD34(+) HSCs and their
      progeny, as well as in other human cell types. Thus, such dual-promoter LVs can
      coexpress multiple transgenes efficiently in a single target cell and will enable
      many gene transfer applications.

PMID- 12788658
TI  - Helper virus-free, optically controllable, and two-plasmid-based production of
      adeno-associated virus vectors of serotypes 1 to 6.
AB  - We present a simple and safe strategy for producing high-titer adeno-associated
      virus (AAV) vectors derived from six different AAV serotypes (AAV-1 to AAV-6).
      The method, referred to as "HOT," is helper virus free, optically controllable,
      and based on transfection of only two plasmids, i.e., an AAV vector construct and
      one of six novel AAV helper plasmids. The latter were engineered to carry AAV
      serotype rep and cap genes together with adenoviral helper functions, as well as
      unique fluorescent protein expression cassettes, allowing confirmation of
      successful transfection and identification of the transfected plasmid. Cross
      packaging of vector DNA derived from AAV-2, -3, or -6 was up to 10-fold more
      efficient using our novel plasmids, compared to a conservative adenovirus
      dependent method. We also identified a variety of useful antibodies, allowing
      detection of Rep or VP proteins, or assembled capsids, of all six AAV serotypes.
      Finally, we describe unique cell tropisms and kinetics of transgene expression
      for AAV serotype vectors in primary or transformed cells from four different
      species. In sum, the HOT strategy and the antibodies presented here, together
      with the reported findings, should facilitate and support the further development
      of AAV serotype vectors as powerful new tools for human gene therapy.

PMID- 12788659
TI  - Treatment of relapsed malignant glioma with an adenoviral vector containing the
      herpes simplex thymidine kinase gene followed by ganciclovir.
AB  - Between November 1998 and December 2001, we treated 14 patients with advanced
      recurrent high-grade gliomas with a total dose of 4.6 x 10(8), 4.6 x 10(9), 4.6 x
      10(10), or 4.6 x 10(11) viral particles (VP) of a replication-incompetent
      adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven
      by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir
      (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was
      administered by 50 intraoperative wound-bed injections of 0.2 ml each (total
      volume 10 ml). The study's primary objective was to determine the safety of this
      treatment and establish the maximum tolerated dose (MTD). Injection of all doses
      of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached.
      All patients had recurrence or progression of the tumor 1-24 months (median 3.5
      months) after gene therapy. The overall median survival was 4 months. Four
      patients survived longer than 1 year following gene therapy. One patient is still
      alive, with histologically confirmed progression of the tumor, 29 months after
      treatment. Ten patients died within 8 months of treatment, all from progression
      of the tumor. In 5 patients residual and measurable tumor was visible on the
      direct (<48 h) postoperative MRI. No objective radiological response was
      documented on subsequent MRI. None of the patients came to autopsy. In
      conclusion, the administration of 4.6 x 10(11) VP of IG.Ad.MLPI.TK by 50
      injections into the wound bed following resection of recurrent malignant glioma,
      followed by GCV treatment, was well tolerated.

PMID- 12788660
TI  - Aortomyoplasty: hemodynamics and comparison to the intraaortic balloon pump.
AB  - BACKGROUND: Aortomyoplasty (AMP), a procedure in which the latissimus dorsi
      muscle (LDM) is wrapped around the aorta and stimulated during diastole, is a
      potential method of chronic counterpulsation. Counterpulsation by the intraaortic
      balloon pump (IABP) is a proven treatment for ischemic coronary syndrome and
      heart failure but cannot be used chronically. This study examined the long-term
      potential of a unique AMP configuration and compared its performance to the IABP.
      MATERIALS AND METHODS: AMP was done using a wringer configuration (AMP-W) in nine
      dogs. Six and 12 months later, acute hemodynamic augmentation was evaluated by
      measuring differences in mean diastolic aortic pressure (mDAP), peak left
      ventricular pressure (pLVP), and the endocardial viability ratio (EVR) between
      stimulated and unstimulated beats. RESULTS: The diastolic augmentation obtained
      by AMP-W at 6 months and by AMP-W and IABP at 12 months was statistically
      significant. Additionally, the enhancements in EVR (16.1 +/- 4.3%), mDAP (8.6 +/-
      2.5%), and pLVP (-1.8 +/- 1.0%) at 6 months were similar to those in EVR (19.1 +/
      5.2%), mDAP (13.1 +/- 3.6%), and pLVP (-0.8 +/- 1.3%) at 12 months. Most
      importantly, the augmentation obtained by AMP-W at 12 months was similar to that
      of the IABP: EVR (17.1 +/- 5.9%), mDAP (13.4 +/- 6.7%), and pLVP (-1.5 +/- 0.8%).
      CONCLUSIONS: AMP-W is a safe, robust procedure, capable of providing
      counterpulsation equivalent to the IABP, 12 months following surgery. The
      potential for AMP-W to offer chronic counterpulsation and to benefit the ischemic
      heart should be investigated further.

PMID- 12788661
TI  - Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.
AB  - BACKGROUND: Cellular functions are maintained by a continuous supply of ATP,
      which is supplied efficiently by mitochondrial oxidative phosphorylation. Since
      myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the
      liver, facilitates oxygen diffusion under low oxygen conditions and enhances
      oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and
      attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated
      myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent
      livers with adenovirus carrying CMV promoter sequences linked to the human
      myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for
      myoglobin, and cellular and hepatic ATP levels were examined. The effect of
      myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat.
      RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after
      AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h
      after AdCMVMyo transfection were significantly higher than control levels and
      those after adenovirus-mediated beta-galactosidase transfection. Finally,
      expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver.
      CONCLUSION: These results indicate that myoglobin gene transfer to the liver
      enhanced ATP levels both in vitro and in vivo and might be a novel strategy to
      reduce ischemia-reperfusion injury.

PMID- 12788662
TI  - Melatonin and vitamin D3 increase TGF-beta1 release and induce growth inhibition
      in breast cancer cell cultures.
AB  - BACKGROUND: Evidence has accumulated that 1,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] is involved in the regulation of the proliferation of breast tumor
      cells. For complete tumor suppression high hypercalcemic doses of 1,25
      (OH)(2)D(3) are needed. The aim of this study was to assess the effect of
      combined treatment of 1,25-(OH)(2)D(3) at low doses and melatonin (MEL) on the
      proliferation of estrogen-responsive rat breast cancer cell line RM4. MATERIALS
      AND METHODS: RM4 cell proliferation was assessed by [3H]thymidine uptake. The
      presence of TGF-beta(1) in serum-free conditioned medium was determined by
      inhibition antibody binding assay. RESULTS: In 17-betaE cultured RM4 cells both
      MEL and 1,25-(OH)(2)D(3) alone and in combination significantly reduced
      [3H]thymidine incorporation in a dose-related fashion. MEL by itself was
      ineffective in inhibiting the FCS-cultured RM4 cells, while 1,25-(OH)(2)D(3)
      strongly inhibited [3H]thymidine incorporation. Meanwhile, MEL increased the
      sensitivity of the FCS-cultured RM4 cells to 1,25-(OH)(2)D(3) in the combined
      regimen, from 20- to 100-fold. MEL significantly enhanced the TGF-beta(1)
      secretion from RM4 cells and vitamin D(3) increased the TGF-beta(1) secretion in
      a dose-dependent manner, from 2- to 7-fold. Moreover, a further enhancement of
      the TGF-beta(1) release was obtained with the combined treatment, but only for
      low 1,25-(OH)(2)D(3) concentrations. The addition of monoclonal anti-TGF-beta(1)
      antibody to the medium of RM4 cells exposed to vitamin D(3) alone or in
      combination with MEL increased the [3H]thymidine uptake compared to the
      correspondent cells cultured without antibody. CONCLUSIONS: Our data point to a
      potential benefit of combination therapy with 1,25-(OH)(2)D(3) and MEL in the
      treatment of breast cancer and suggest that the growth inhibition could be
      related, at least in part, to the enhanced TGF-beta(1) secretion.

PMID- 12788663
TI  - Docosahexaenoic acid selectively augments muscarinic stimulation of epithelial Cl
      secretion.
AB  - BACKGROUND: We investigated the effect of various fatty acids on electrogenic
      chloride secretion in T84 cells, a model for intestinal epithelium. MATERIALS AND
      METHODS: T84 intestinal epithelial cells grown on permeable supports were studied
      by conventional current-voltage clamping. Membrane lipids from T84 cells were
      extracted, transmethylated, and analyzed by gas chromatography. Lipid extracts
      were fractionated into nonpolar, free fatty acids, and phospholipids by
      amynopropil column chromatography. RESULTS: Docosahexaenoic acid (DHA) but not
      eicosapentanoic acid or other fatty acids selectively enhanced the secretory
      response to the muscarinic agonist carbachol but not the response to other Ca2+
      agonists (histamine, thapsigargin, or ionomycin) or the response to the cAMP
      agonist forskolin. The ability of DHA to augment Cl- secretion appeared to
      correlate closer with free DHA levels than with membrane-bound DHA. Other effects
      of DHA on T84 cells included a reduction in transepithelial resistance (a measure
      of barrier function), actions that were dissociated from the effect on Cl-
      secretion. CONCLUSION: The results suggest that DHA, which has been shown to
      reverse organ pathology in experimental cystic fibrosis, may selectively affect
      agonist-regulated transport events and other fundamental properties of epithelial
      cells.

PMID- 12788664
TI  - Chronic high pressure potentiates the antiproliferative effect and abolishes
      contractile phenotypic changes caused by endothelial cells in cocultured smooth
      muscle cells.
AB  - High in vitro pressures have been reported to alter smooth muscle cell (SMC) and
      endothelial cell (EC) phenotype, while endothelial cells (ECs) can influence the
      proliferation, phenotype, and contractile features of smooth muscle cells (SMC)
      in coculture systems. However, little is known about the in vitro effects of
      pressure on EC/SMC cocultures. We therefore sought to compare SMC proliferation
      in independent and EC coculture under ambient and high pressure, and identify
      changes in the contractile phenotype of SMCs by measuring levels of the L-type
      Ca(2+) channel a(1) subunit (dihydropyridine-DHP receptor) which is critical for
      Ca(2+) transients, differentiation and contractility in SMC. METHODS: Rat aortic
      SMCs in independent culture (SMC/0) and coculture with ECs (SMC/EC) were
      maintained in 5% CO(2) under either atmospheric or high pressure (130 mmHg). SMC
      were counted at 0, 1, 3, and 5 days and compared to initial cell counts of day 0
      before the exposure to experimental conditions. DHP receptor levels were
      quantitated by Western blotting (three similar studies). RESULTS: ECs suppressed
      SMC proliferation on day 1 of coculture in both atmospheric and high pressure
      (20% inhibition vs independent culture, P < or = 0.05). By day 3, cocultured SMC
      under atmospheric pressure displayed no EC-mediated inhibition, and at day 5,
      atmospheric cocultured SMCs revealed statistically significant enhanced
      proliferation as compared with SMCs in independent cultures. However, cocultured
      SMCs exposed to 130 mmHg pressure displayed sustained sensitivity to EC growth
      inhibition at both days 3 and 5 of the experiment. Coculture decreased SMC DHP
      receptor levels under atmospheric pressure. However, this effect was abolished in
      cocultures exposed to high pressure. CONCLUSIONS: High pressure substantially
      alters the regulatory influence of EC on SMC proliferation and contractile
      potential. This pressure/coculture model should increase our understanding of
      cellular interaction in hypertensive vasculopathy.

PMID- 12788665
TI  - Sepsis alters vessel contraction by adrenoceptor-induced nitric oxide and
      prostanoid.
AB  - BACKGROUND: Alpha-adrenergic agents contract vascular smooth muscle (VSM) and
      stimulate endothelial release of secondary factors which modulate VSM
      contraction. Our study examined constrictor prostanoid (cPN) and nitric oxide
      (NO) as secondary factors which could alter alpha-1 adrenoceptor-mediated
      contraction during sepsis. METHODS: Sepsis was induced in rats by inoculation of
      an implanted sponge with Escherichia coli and Bacteroides fragilis. Aortic rings
      at 24 h from septic (n = 21) and control (n = 21) rats were suspended in
      physiological salt solution (PSS) with or without blockers to NO (N(G)
      monomethylarginine), cPN (mefenamic acid, MFA), or thromboxane A2 (SQ29548).
      Contraction dose-response curves were generated to determine maximal contraction
      force (F(max)) and pD2 (sensitivity) to phenylephrine in each experimental group.
      RESULTS: Sepsis increased F(max) to phenylephrine (PHE) (1.18 vs 0.90 g, SEM
      0.0703). COX inhibition reduced the F(max) in control (0.63 vs 0.90 g, SEM
      0.0675) but not in septic animals (1.19 vs 1.18 g, SEM 0.0433). TXA2 receptor
      inhibition did not alter F(max) in control (1.017 vs 0.973 g, SEM 0.0959) or
      septic animals (1.28 vs 1.12 g, SEM 0.0823). NOS inhibition enhanced the F(max)
      in both nonseptic (2.03 vs 0.83 g, SEM 0.0523) and septic rats (1.96 vs 1.15 g,
      SEM 0.0526), but did less so in the septic animals. CONCLUSIONS: PHE-induced
      F(max) is determined by a balance between PHE-stimulated VSM alpha-adrenoceptor
      activity, and PHE-stimulated endothelial release of cPN and NO. Sepsis enhances
      total PHE-induced F(max) by increasing VSM alpha-adrenoceptor activity and
      reducing PHE-stimulated endothelial release of dilator NO. Sepsis abolishes the
      PHE-stimulated endothelial release of cPN. PHE-stimulated cPN is not thromboxane
      A2, but could be a nonprostanoid dilator in the lipoxygenase (HETE) or cytochrome
      P450 (EET) pathways.

PMID- 12788666
TI  - Immune-enhancing enteral diet increases blood flow and proinflammatory cytokines
      in the rat ileum.
AB  - BACKGROUND: Enteral feeding improves outcome following surgery. Benefits depend
      on timing, route (enteral vs parenteral), and nutrient composition (standard vs
      immune-enhancing diets; IED). IED augments intestinal immunity and stimulates gut
      blood flow during absorption in a nutrient-specific manner. We hypothesize that a
      mechanism for the gut protective effect of IED is augmentation of blood flow to
      the gut-associated lymphoid tissue (GALT) in the terminal ileum. METHODS: Male
      Sprague-Dawley rats (200-230 g) were fed for 5 days either an IED (Impact,
      Novartis) or an isocaloric, isonitrogenous control diet (CD, Boost, Mead-Johnson)
      matched to the daily caloric intake (rat chow). Rats were then anesthetized and
      cannulated for microsphere determination of whole organ blood flow. Blood glucose
      levels and blood flow to abdominal organs were determined at baseline and 30, 60,
      90, and 120 min after gastric gavage (2 ml) with IED or CD. Intestinal tissues
      were harvested for cytokine levels (ELISA: IL-4, IL-10, IFN-gamma, and IgA).
      RESULTS: Chronic IED increased baseline blood flow in the distal third of the
      small intestine compared to chow-fed and CD. Baseline blood flow was comparable
      between IED and CD in all other organs. CD and IED produced different blood flow
      patterns after gavage. CD increased blood flow compared to baseline and IED in
      antrum, duodenum, and jejunum. Ileal blood flow remained elevated in IED rats for
      2 h, perhaps suggesting maximal blood flow. IED increased blood glucose compared
      to CD. Chronic IED increased IL-4 and decreased IL-10 in the terminal ileum.
      CONCLUSIONS: Chronic IED exposure increases and sustains ileal blood flow
      compared to CD with altered proinflammatory cytokine expression. Our data suggest
      that a mechanism for the IED effect involves the selective perfusion of the
      terminal ileum and contiguous GALT during IED nutrient absorption.

PMID- 12788667
TI  - Attenuated metabolic response to surgery in tumor-bearing rats.
AB  - BACKGROUND: During cancer, proteins are chronically wasted, including proteins of
      the gut. Surgical stress acutely increases protein breakdown of the gut. Surgery
      in cancer patients may thus have a double effect on the gut and lead to
      exhaustion and functional loss of the gut. METHODS: Female Lewis rats (+/-200 g)
      were studied bearing a subcutaneous tumor or after sham implantation.
      Hysterectomy was performed in half of the rats as a standardized operative
      procedure. Postoperative protein kinetics of the gut were determined using a
      primed constant infusion of L-[2,6-(3)H]-phenylalanine. Gut function was assessed
      by testing its permeability for sugar probes lactulose and L-rhamnose. Villus
      height and crypt depth were measured and polyamine concentrations were measured
      as markers for mucosal proliferation and differentiation. RESULTS: In control
      rats, gut protein breakdown increased from 6 +/- 3 to 32 +/- 8 nmol phenylalanine
      x 100 g body wt x min after hysterectomy. This was accompanied by increased amino
      acid membrane transport rates and metabolic shunting. In tumor-bearing rats,
      increased protein breakdown in response to surgery was attenuated (8 +/- 4 vs 17
      +/- 4 nmol x 100 g body wt x min). Surgery increased the lactulose/L-rhamnose
      recovery ratio, indicating increased gut permeability. In the presence of a tumor
      gut permeability also increased and it increased further after surgery. No
      changes in villus height or polyamine levels could explain the increased
      permeability of the gut. CONCLUSION: The study shows that a mild surgical trauma
      increases protein breakdown of the gut and simultaneously increases gut
      permeability. In the presence of a tumor the metabolic response to surgery is
      attenuated. Gut barrier loss was highest in the combined presence of cancer and
      the surgical insult.

PMID- 12788668
TI  - The protective mechanism of magnolol, a Chinese herb drug, against warm ischemia
      reperfusion injury of rat liver.
AB  - BACKGROUND: Cell apoptosis following warm ischemia-reperfusion injury is a major
      concern in clinical issues such as organ transplantation, trauma, and cardiogenic
      shock. The purpose of this study was to evaluate the possible role of magnolol, a
      Chinese herb drug, in apoptotic injury and the kinetic expression of apoptotic
      related genes in rat livers subjected to warm ischemia-reperfusion (WI/R).
      MATERIALS AND METHODS: Three weeks prior to the experiment 10 rats underwent a
      portosystemic shunt operation according to Bengmerk's method. The rats were
      divided into three groups. Group 1 (GI) was the control group, Group 2 (GII) and
      Group 3 (GIII) the magnolol-treated groups. GI and GII were subjected to 2 h and
      GIII to 3 h of WI/R by clamping the portal vein and hepatic artery under ether
      anesthesia. RESULTS: Results show that all the control rats died after 2 h WI/R.
      Apoptotic cells were detected under microscopy as well as by DNA assay. Magnolol
      treated groups tolerated warm ischemia-reperfusion for 2 h and significantly less
      apoptotic cells were observed (198 +/- 22 vs 42.6 +/- 28). But magnolol-treated
      rats could not tolerate 3 h warm ischemia-reperfusion. RT-PCR of liver tissue
      shows that there is an upregulated expression of the anti-apoptotic Bcl-xL gene
      and suppression of the Bcl-xS gene in GII. CONCLUSION: Magnolol has an anti
      apoptotic effect and protects the liver against WI/R for 2 h but not for 3 h
      through upregulation of the anti-apoptotic Bcl-XL gene and suppression of the Bcl
      xS gene.

PMID- 12788669
TI  - Matrix metalloproteinase expression in breast cancer.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated as possible
      mediators of invasion and metastasis in some cancers. Our objective was to
      investigate which MMPs were constitutively expressed in breast tumor cells versus
      those that could be up-regulated by a number of agents known to affect MMP
      expression in other cell systems. METHODS: We evaluated expression of MMPs 1-16
      in breast tumor cell lines MDA-MB-231, T47D, and MCF-7 using semiquantitative RT
      PCR and gelatin zymography. Exposure to 12-O-tetradecanoylphorbal-3-acetate
      (TPA), concanavalin-A (Con-A), the fibronectin-mimetic peptide GRGDSP (RGD),
      extracellular matrix (ECM) components, and anti-integrin antibodies was used to
      test for possible MMP up-regulation. Mitogen-activated protein kinase inhibitors
      (MAPK-I) were used to evaluate signal transduction pathways and regulation of MMP
      expression. RESULTS: MMPs 1, 2, 7-11, 13, 14, and 16 were constitutively
      expressed in some tumor cell lines but not in normal breast epithelial cells.
      Administration of TPA, Con-A, and RGD increased the expression of MMPs 1, 2, 9,
      and 10. No MMP up-regulation was seen in MDA-MB-231 or MCF-7 after exposure to
      ECM components or after exposure to anti-integrin antibodies. MAPK-I had no
      effect on constitutive MMP expression but reduced or abolished the TPA up
      regulation of MMP-9 in MDA-MB-231 and MCF-7. CONCLUSIONS: Breast tumor cell lines
      constitutively express a number of MMPs. Because MMP expression can be up
      regulated by Con-A, the fibronectin-mimetic peptide RGD, and TPA while being
      susceptible to inhibition by MAPK antagonists, MAPK signaling appears to play a
      role in this expression.

PMID- 12788670
TI  - Androgen blockade enhances response to melanoma vaccine.
AB  - BACKGROUND: Because preclinical studies suggest an interaction between androgens
      and the immune system, we used a murine model to determine whether androgen
      blockade with flutamide might enhance the immunogenicity of an irradiated
      melanoma cell vaccine. MATERIALS AND METHODS: Forty C57BL/6 male mice were
      randomly assigned to four treatment groups: flutamide + RPMI (Group A), flutamide
      + irradiated B16 murine melanoma cells (Group B), placebo + RPMI (Group C), and
      placebo + irradiated B16 cells (Group D). Splenocyte proliferation and secretion
      of interleukin-2 and interferon-gamma were assayed after coculturing splenocytes
      with irradiated B16 cells. Antibody-dependent cellular cytotoxicity (ADCC)
      against B16 cells was determined using peripheral blood lymphocytes. To examine
      the effect of treatment on tumor growth, a second set of 40 mice assigned to
      Groups A, B, C, and D underwent tumor challenge 7 days after the last treatment.
      RESULTS: Splenocyte proliferation was significantly higher in the two groups
      receiving flutamide at 50 mg/kg x 7 days (29% in Groups A and B vs 3% in Group C
      and 7% in Group D). Secretion of interferon was significantly higher in mice
      receiving flutamide + irradiated B16 cells (15.2 pg/ml in Group B vs 0, 1.7, and
      4 pg/ml in Groups A, C, and D, respectively; P = 0.0024). Differences in
      interleukin secretion were not significant. ADCC was 26% in Group B vs 15, 8, and
      22% in Groups A, C, and D, respectively (P = 0.0001). In the tumor challenge
      experiment, the rate of survival was 10% higher in mice receiving irradiated B16
      + flutamide than in mice receiving irradiated B16 alone. CONCLUSION: Flutamide
      can enhance immune responses to an irradiated whole-cell melanoma vaccine. A
      clinical study of immunotherapeutic androgen blockade is warranted.

PMID- 12788671
TI  - BCL-2 and BAX expression and cell proliferation, after partial hepatectomy with
      and without ischemia, on cholestatic liver in rats: an experimental study.
AB  - BACKGROUND: Liver regeneration after partial hepatectomy (PHx) is regulated by
      several factors that activate or inhibit hepatocyte proliferation. Apoptosis
      seems to play an important role in cellular proliferation and liver regeneration.
      This study investigates the expression apoptosis-associated genes bcl-2 and bax,
      and the presence of apoptosis and cell proliferation after PHx, in normal and
      jaundiced rats with or without superimposed ischemia. MATERIALS AND METHODS: The
      study included 50 male Wistar rats assigned into; five groups (10 rats each). On
      day 0, rats of groups II, IV, and V underwent common bile duct ligation (BDL). On
      day 10, total liver ischemia (TLI) (occlusion of hepatic artery and portal vein
      TLI) for 30 min was performed on animals of group V. When TLI was completed, all
      30 animals (of groups I, IV, and V) underwent PHx (68%). Animals of group III
      underwent only TLI for 30 min. Rats of groups I, IV, and V were sacrificed 24 and
      48 h after PHx was completed. Rats of group II were sacrificed 10, 11, and 12
      days after BDL. Rats of group III were sacrificed immediately, 24 and 48 h after
      TLI completion. Liver tissue was obtained and pathologic examination included:
      (a) H&E stain, (b) in situ hybridization (detection of bcl-2 and bax mRNA) in
      paraffin sections, (c) Western blot analysis for the evaluation of bcl-2 and bax
      protein levels, (d) in situ hybridization (TUNEL) for the detection of apoptotic
      bodies, and (e) immunohistochemical stains (streptavidin-biotin method) in
      paraffin sections to detect cells that (i) express bcl-2 and bax proteins and
      (ii) undergo proliferation (Ki67+ cells). Results were expressed following
      morphometric analysis. RESULTS: Before hepatectomy, bcl-2 (protein or mRNA)
      levels were higher in jaundiced rats vs controls. Furthermore, bax (protein or
      mRNA) levels and apoptotic body index (ABI) were higher in cholestatic livers.
      After hepatectomy, there was an early decrease in the protein and mRNA levels of
      antiapoptotic gene bcl-2 and a late increase of proapoptotic gene bax and the
      ABI, compared to controls. Cell proliferation of hepatocytes was lower in group V
      (BDL + TLI) compared to that of groups II and IV (BDL). CONCLUSIONS: This study
      shows that apoptosis takes place in cholestatic livers with or without
      superimposed ischemia and may contribute in the impaired regenerative response
      observed in livers of jaundiced rats after partial hepatectomy.

PMID- 12788672
TI  - Successful transplantation of a 20% partial liver graft in rats: a technical
      innovation.
AB  - BACKGROUND: Graft-size disparity negatively impacts the postoperative outcome in
      the setting of adult-to-adult living donor liver transplantation. MATERIALS AND
      METHODS: As a model for partial liver transplantation in rats using a minimized
      graft volume, we orthotopically transplanted a 20% reduced-size liver with the
      two-cuff method. Blood chemistry, graft weight restoration, and labeling indices
      of 5-bromo-2'-deoxyuridine were estimated. RESULTS: We achieved 100% 2-week
      survival. Hepatic mass was restored rapidly with early normalization of
      biochemical parameters, although albumin synthesis capacity required more time to
      recover. CONCLUSION: This technique has great potential for research as well as a
      therapeutic approach to regeneration and functional recovery of small liver
      grafts under various posttransplant circumstances.

PMID- 12788673
TI  - Endotoxin impairs endothelium-dependent vasodilation more in the coronary and
      renal arteries than in other arteries of the rat.
AB  - Endotoxemia may result in endothelial dysfunction, and some vascular beds may be
      affected more than others. To test this hypothesis, we studied, in vitro, the
      reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic
      arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at
      37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the
      vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary
      artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh)
      in preconstricted vessels. Although differing between vessel types, the smooth
      muscle contractile responses were not affected by endotoxin, either in the
      presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat
      coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in
      endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in
      control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a
      mean 55% decrease vs controls in coronary and a mean 35% decrease in renal
      arteries. Endotoxin did not affect superior mesenteric and hepatic arteries.
      Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial
      NO synthase, independent of iNOS. The increase in heterogeneity among endothelium
      dependent vasodilation after endotoxin may help to explain early blood flow
      maldistribution in endotoxin shock.

PMID- 12788674
TI  - Integrating the communicative predicament and enhancement of aging models: the
      case of older Native Americans.
AB  - This article addresses issues of diversity in intergenerational communication by
      introducing a model that integrates key aspects of the communication predicament
      and enhancement models of aging with other potent constructs (e.g., group
      vitality, mindfulness). The model is then applied to the health care experience
      of an understudied population-older Native Americans. Specifically, it is used to
      illuminate how intergenerational communication may be facilitated or, indeed,
      hindered by communicative processes born out of categorization and stereotyping.
      Health care professionals (in particular), whose working environment is
      increasingly populated by older economically, culturally, and ethnically diverse
      patients, should be made aware of some of the strengths and weaknesses of their
      communicative practices in such intergenerational interactions.

PMID- 12788675
TI  - The relationship between college students' schema regarding alcohol use, their
      television viewing patterns, and their previous experience with alcohol.
AB  - Two hundred college students participated in an experiment investigating how
      individuals use television and real world experiences to construct alcohol use
      schema. Students were asked to write a story about a student who had a difficult
      day and, on arriving home, fixed himself a drink. In randomly assigned
      conditions, directions led the student to believe this was to be either a real
      world scenario or the setting for a television episode. Stories were coded for
      setting and social nature of use, quantity of use, consequences (both severity
      and valence), and overall tone. In general, stories characterized alcohol use as
      heavy, social, relaxing, and resulting in mostly minor consequences. Story
      characteristics did not differ based on direction type (real world vs. TV
      scenario). Students also completed a series of measures regarding television
      viewing habits, attitudes about alcohol use, and past experiences with use.
      Regarding television viewing patterns, those who watched more television overall
      created stories with more alcohol use. Viewing of dramas in particular was
      associated with less severe consequences as a result of use. In terms of personal
      experience with use, individuals who had driven under the influence of alcohol
      were more likely to construct a story with a positive tone and those who had
      passed out from drinking were less likely to conclude their stories with a moral
      tale discouraging drinking. The conclusion of this research is that both personal
      and observed experiences are important influencing factors in individuals' schema
      regarding alcohol use.

PMID- 12788676
TI  - A radio-based approach to promoting gun safety: process and outcome evaluation
      implications and insights.
AB  - Three radio public service announcements (PSA) were created to increase knowledge
      of 10 gun-safety practices in a mid-Michigan county. Concurrently, a direct-mail
      coupon highlighting the same gun-safety practices was disseminated to over 70,000
      households in the same county. Results of a telephone survey indicate that,
      compared to unexposed individuals, those who were exposed to the PSA were able to
      name significantly more gun-safety practices. Specifically, significant
      differences between those exposed to the PSA versus those not exposed were found
      for 5 gun-safety practices, as well as for a 4-item index measuring gun locking
      and storage behaviors, and a 9-item index that included all gun-safety practices.

PMID- 12788677
TI  - The use of humor in promoting positive provider-patient interactions in a
      hospital rehabilitation unit.
AB  - Humor within the health care setting apparently can serve to facilitate positive
      patient-provider interactions and to create a patient-centered environment. This
      article provides an ethnographic account of patient-provider interactions held
      during therapeutic activity sessions within a hospital unit (MIRTH) designed to
      promote therapeutic humor. This study's findings suggest that humor in these
      activity sessions was mainly a by-product of more predominant effects, such as
      patients' positive attitude and happiness. Whereas MIRTH used contrived humor to
      portray its identity as a humor unit, staff and patients also took advantage of
      spontaneous humor that emerged out of interactions. Humor appeared secondary to
      the primary outcome of promoting patients' happiness and well being.

PMID- 12788678
TI  - The impact of invisible illness on identity and contextual age across the life
      span.
AB  - This study explored the impact invisible illness has on identity, specifically
      contextual age, throughout the life span. It was grounded in the assumption that
      an individual's identity is formed through communicative interaction. Using
      social identity theory (Tajfel & Turner, 1986) as a framework, individuals'
      identities after disclosure of invisible illness were explored. Rubin and Rubin's
      (1986) Contextual Age Questionnaire was used to determine self-perceived as well
      as other-perceived contextual age. Invisibly ill individuals reported
      significantly "higher" contextual age scores than did same chronologically aged,
      matched non-ill individuals. In addition, the friends of invisibly ill
      individuals reported "higher" contextual age scores for the invisibly ill
      individuals than the self-reported scores of the same chronologically aged non
      ill individuals. Interviews further revealed that illness instilled insight and
      that disclosure of illness provoked comments from others that led invisibly ill
      individuals to identify with older individuals. Future directions and limitations
      of this study are also discussed.

PMID- 12788679
TI  - Adolescent reactance and anti-smoking campaigns: a theoretical approach.
AB  - Children between the ages of 9 and 15 are a high-risk group for tobacco use. The
      Centers for Disease Control estimates that first use of cigarettes among
      adolescents has risen 30% over the past decade, and that more than 1.2 million
      people age < 18 became daily smokers in 1996 alone. Moreover, research indicating
      that awareness and liking of cigarette advertisements is higher among adolescents
      than adults underscores the need to devote more effort to understanding reactions
      to tobacco-related messages. Adding to this problem is the fact that the early
      gains of some successful anti-tobacco interventions disappear as adolescents age.
      Drawing on the theory of psychological reactance, a number of hypotheses were
      tested that addressed the impact of pro- and anti-smoking messages on a variety
      of outcomes, including participants' intended behaviors, evaluation of message
      sources, and seeking of disconfirming information. All the messages were created
      and delivered to 4th-, 7th-, and 10th-grade students via personal computers. The
      pattern of results supports the theoretically derived hypotheses, indicating that
      grade level and message type had a significant impact on the processing of
      tobacco-related messages. Implications and suggestions for future tobacco
      prevention campaigns are discussed.

PMID- 12788680
TI  - Neurobehavioral functioning of persons with Parkinson's disease.
AB  - This study examines the neurobehavioral functioning of persons with Parkinson's
      disease (PD) using the Neuropsychology Behavior and Affect Profile (NBAP), a self
      report version of the Neurobehavioral Rating Scale (NRS-Revised), and the
      Dysexecutive Questionnaire (DEX). In the absence of existing data, the
      psychometric properties of these measures were assessed prior to examining
      neurobehavioral functioning. Self- and observer report versions of the NBAP, NRS
      Revised, and DEX were administered to a group of 30 persons with PD and 30
      matched controls. Reliability analyses revealed that, although the total scores
      from these measures provided internally reliable assessments of neurobehavioral
      functioning, the sub-scale scores of the NBAP demonstrated lower reliability. In
      addition, the 3 measures of neurobehavioral functioning showed moderate to high
      correlations with one another and with measures of disease severity. When the PD
      and control groups were compared on measures of current neurobehavioral
      functioning, the PD group was found to exhibit problems on the NRS-Revised. Since
      the onset of their disease, the PD group showed increasing levels of depression,
      inappropriate behavior, and a reduced ability to follow the subtleties of
      communication as measured by the NBAP. There was good agreement between self- and
      observer-reports of neurobehavioral functioning, suggesting that problems with
      insight did not affect patients' reports of symptomatology. Overall, the findings
      indicate the emergence of a number of neurobehavioral problems in the early
      stages of PD that are likely to adversely affect the social interactions of
      persons with PD. When combined with the motor and cognitive effects of PD, these
      problems may lead to social isolation.

PMID- 12788681
TI  - Verbal fluency declines after pallidotomy: an interaction between task and lesion
      laterality.
AB  - Verbal fluency declines are commonly reported after pallidotomy in patients with
      Parkinson's disease. However, it is not clear whether there is an interaction
      between side of surgery and task format (lexical vs. semantic) or whether error
      rates (perseverations, intrusions, rule violations) increase after surgery. This
      study examined verbal fluency before and approximately 4 months after unilateral
      pallidotomy. The left and right pallidotomy groups were matched on key
      demographic, cognitive, and disease variables. Pallidotomy resulted in a decline
      in lexical but not semantic verbal fluency, and this decline was most evident in
      the left-sided surgery group. Error rates (perseverations, intrusions, and rule
      violations) were not affected by pallidotomy. Findings support the role of left
      frontal-basal ganglionic circuits in word retrieval processes and/or lexical
      search and access.

PMID- 12788682
TI  - Tracking cognitive functioning over time: ten-year longitudinal data from a
      community-based study.
AB  - Over 10 years, a community-based sample age 65> or = years, with a starting
      cohort size of 1,206, was assessed biennially with the Mini-Mental State Exam;
      the Consortium to Establish a Registry for Alzheimer's Disease battery; Immediate
      and Delayed Recall of a Story; Verbal Fluency for P and S, Fruits and Animals;
      Clock Drawing; Temporal Orientation; and Trail Making tests. We report
      distributions of scores over time, at each wave, in (a) all individuals who were
      assessed at that wave, whether or not they participated in all waves, and (b) the
      Survivor subgroup of 425 participants who completed all tests at all 5 waves.
      Scores and factor structures remained remarkably stable over the study period.
      The most marked decline over time was seen on the Trail Making tests. As the
      survivors are de facto a largely healthy and motivated group, their data can be
      considered population-based healthy norms and may serve as a reference for other
      studies conducting repeated evaluations using the same tests.

PMID- 12788683
TI  - Impairments in dichotic listening in patients presenting anterior communicating
      artery aneurysm.
AB  - Impaired dichotic listening has been documented in numerous etiologies, but there
      is limited information on patients who present with anterior communicating artery
      (ACoA) aneurysm. The sequelae following ACoA aneurysm is frequently associated
      with neurobehavioral impairments, such as confabulation, memory, and behavior, as
      a result of the areas of innervation (DeLuca, 1992; DeLuca & Diamond, 1995).
      Clinical experience, however, shows ACoA aneurysm to also be associated with
      impairments in dichotic listening. Participants in this study were divided into 2
      groups: patients who presented with ACoA aneurysm with age-matched controls, and
      patients who presented moderate to severe traumatic brain injury (TBI) with age
      matched controls. TBI patients were included for test-validity purposes and to
      allow a comparison between diffuse and focal cerebral damage. Dichotic listening
      results revealed a similar pattern for patients with ACoA aneurysm and those with
      brain injury. The findings suggest that central auditory pathways are susceptible
      to damage following ACoA aneurysm.

PMID- 12788684
TI  - Cognitive function in people with chronic illness: inflammatory bowel disease and
      irritable bowel syndrome.
AB  - Recent research has shown that people with chronic illnesses often experience
      cognitive deficits, such deficits may be specific to a particular type of
      illness, reflecting the disease process itself, or they may be deficits that are
      common across a number of chronic illnesses. Our study investigated whether
      people with an organic disease (Inflammatory Bowel Disease) show cognitive
      dysfunction relative to the control group and people with a functional illness
      (Irritable Bowel Syndrome), and if so, to elucidate the mechanisms by which such
      dysfunction occurs. A quasi-experimental design using three groups of
      participants provided scores on IQ, memory, and cognitive flexibility.
      Differences in absolute scores were slight. However, a noticeable interaction
      effect was found between group and IQ: The illness groups showed a deficit in
      verbal IQ relative to both their own performance IQ and to that of the control
      group's verbal IQ. This verbal deficit cannot be explained by depression,
      cognitive load, or medication.

PMID- 12788685
TI  - Neuropsychological differentiation of late-onset schizophrenia and dementia of
      the Alzheimer's type.
AB  - Late-onset schizophrenia and dementia of the Alzheimer's type (DAT) often present
      with some pathological and behavioral commonalities. Specifically, both illnesses
      may involve varying degrees of delusional manifestation, apathy, lateral/third
      ventricular enlargement, reduced frontal lobe activity, and hippocampal atrophy.
      Moreover, patients with either disease have shown comparable cognitive impairment
      on standardized neuropsychological tests. As such, a differential diagnosis of
      the 2 disorders on the basis of such testing can prove to be difficult. This
      study evaluated the neuropsychological test results of 32 patients with late
      onset schizophrenia and 32 patients with DAT to distinguish the tests that best
      differentiate the 2 disorders. Results indicate that the Wechsler Adult
      Intelligence Scale-Revised Similarities subtest and the California Verbal
      Learning Test (both short- and long-delay free recall) correspond to sensitive
      diagnostic neuropsychological measures. This investigation was preliminary in
      nature, and should aid in the development of a definitive differential profile.

PMID- 12788686
TI  - Reliable change indexes for memory performance in schizophrenia as a means to
      determine drug-induced cognitive decline.
AB  - Some psychotropic medications frequently prescribed in schizophrenia, especially
      agents that contain anticholinergic properties, have adverse effects on learning
      and memory. Given the impact of memory on both functional and symptomatic outcome
      in schizophrenia, it is important to determine if patients suffer from medication
      related memory impairment. This study provides a statistical methodology for
      identifying medication-related changes in memory functioning. Reliable change
      estimates were determined for Rey Auditory Verbal Learning Test performance in 38
      inpatients with schizophrenia. When an 80% confidence criterion was applied,
      improvement or decline of 12 words in the total score (sum score: Trials 1-5)
      cannot be attributed to measurement error. These findings should help clinicians
      better understand cognitive side effects and facilitate decision making regarding
      changes to individual patient's psychopharmacotherapy.

PMID- 12788687
TI  - Trait impressions as overgeneralized responses to adaptively significant facial
      qualities: evidence from connectionist modeling.
AB  - Connectionist modeling experiments tested anomalous-face and baby-face
      overgeneralization hypotheses proposed to explain consensual trait impressions of
      faces. Activation of a neural network unit trained to respond to anomalous faces
      predicted impressions of normal adult faces varying in attractiveness as well as
      several elderly stereotypes. Activation of a neural network unit trained to
      respond to babies' faces predicted impressions of adults varying in babyfaceness
      as well as 1 elderly stereotype. Thus, similarities of normal adult faces to
      anomalous faces or babies' faces contribute to impressions of them quite apart
      from knowledge of overlapping social stereotypes. The evolutionary importance of
      appropriate responses to unfit individuals or babies is presumed to produce a
      strong response preparedness that is overgeneralized to faces resembling the
      unfit or babies.

PMID- 12788688
TI  - Cardiovascular correlates of challenge and threat appraisals: a critical
      examination of the biopsychosocial analysis.
AB  - In this article we examine critically the biopsychosocial (BPS) challenge versus
      threat analysis proposed by Blascovich and his coworkers. We conclude that the
      BPS analysis should be viewed with considerable caution. We conclude this in part
      because the analysis is associated with notable problems, including (a) its
      conception of demand, (b) its definitions of goal-relevant and evaluative
      situations, (c) its assertion regarding primary and secondary appraisal
      determinants of challenge and threat, and (d) its cardiovascular (CV)
      predictions. We conclude this as well because BPS analysis studies have not made
      a compelling empirical case. BPS analysis studies are unpersuasive because (a)
      their CV results are only partially consistent with BPS analysis predictions, (b)
      they have compared CV responses of groups bearing an uncertain relationship to
      the primary and secondary appraisal criteria specified for the production of
      challenge and threat effects, (c) they have not compared challenge and threat
      appraisals between challenge and threat groups, and (d) they provided data that
      are incomplete. Theoretical modifications and additional research could make a
      better case for the BPS view.

PMID- 12788689
TI  - The robust nature of the biopsychosocial model challenge and threat: a reply to
      Wright and Kirby.
AB  - This article responds to Wright and Kirby's (this issue) critique of our
      biopsychosocial (BPS) analysis of challenge and threat motivation. We counter
      their arguments by reviewing the current state of our theory as well as
      supporting data, then turn to their specific criticisms. We believe that Wright
      and Kirby failed to accurately represent the corpus of our work, including both
      our theoretical model and its supporting data. They critiqued our model from a
      contextual, rational-economic perspective that ignores the complexity and
      subjectivity of person-person and person-environmental interactions as well as
      nonconscious influences. Finally, they provided criticisms regarding possible
      underspecificity of antecedent components of our model that do not so much
      indicate theoretical flaws as provide important and interesting questions for
      future research. We conclude by affirming that our BPS model of challenge and
      threat is an evolving, generative theory directed toward understanding the
      complexity of personality and social psychological factors underlying challenge
      and threat states.

PMID- 12788690
TI  - A reflection and evaluation model of comparative thinking.
AB  - This article reviews research on counterfactual, social, and temporal comparisons
      and proposes a Reflection and Evaluation Model (REM) as an organizing framework.
      At the heart of the model is the assertion that 2 psychologically distinct modes
      of mental simulation operate during comparative thinking: reflection, an
      experiential ("as if") mode of thinking characterized by vividly simulating that
      information about the comparison standard is true of, or part of, the self; and
      evaluation, an evaluative mode of thinking characterized by the use of
      information about the standard as a reference point against which to evaluate
      one's present standing. Reflection occurs when information about the standard is
      included in one's self-construal, and evaluation occurs when such information is
      excluded. The result of reflection is that standard-consistent cognitions about
      the self become highly accessible, thereby yielding affective assimilation;
      whereas the result of evaluation is that comparison information is used as a
      standard against which one's present standing is evaluated, thereby yielding
      affective contrast. The resulting affect leads to either an increase or decrease
      in behavioral persistence as a function of the type of task with which one is
      engaged, and a combination of comparison-derived causal inferences and regulatory
      focus strategies direct one toward adopting specific future action plans.

PMID- 12788691
TI  - H as a measure of complexity of social information processing.
AB  - Many studies have used H (a measure of unpredictability derived from information
      theory) to quantify the complexity of descriptions of persons across multiple
      roles. Interpreting these studies is problematic, though, because H confounds
      unpredictability across roles (which is typically the construct of interest) and
      unpredictability within roles (which is simply a function of the proportion of
      traits endorsed). The need to control for unpredictability within roles was
      highlighted by 3 demonstration studies in which controlling for unpredictability
      within roles eliminated relations between well-being and H. I also show how,
      controlling for unpredictability due to the number of traits endorsed and number
      of roles described, H provides a unique measure of role dependence and
      independence. However, H does not measure the type of role overlaps that would
      predict "spillover effects" between roles; therefore, I recommend an alternative
      index of role similarity for future research on spillover effects.

PMID- 12788692
TI  - Hypotonicity induces membrane protrusions and actin remodeling via activation of
      small GTPases Rac and Cdc42 in Rat-1 fibroblasts.
AB  - An important consequence of cell swelling is the reorganization of the F-actin
      cytoskeleton in different cell types. We demonstrate in this study by means of
      rhodamine-phalloidin labeling and fluorescence microscopy that a drastic
      reorganization of F-actin occurs in swollen Rat-1 fibroblasts: stress fibers
      disappear and F-actin patches are formed in peripheral extensions at the cell
      border. Moreover, we demonstrate that activation of both Rac and Cdc42, members
      of the family of small Rho GTPases, forms the link between the hypotonic
      stimulation and F-actin reorganization. Indeed, inhibition of the small GTPases
      RhoA, Rac, and Cdc42 (by Clostridium difficile toxin B) prevents the hypotonicity
      induced reorganization of the actin cytoskeleton, whereas inhibition of RhoA
      alone (by C. limosum C3 exoenzyme) does not preclude this rearrangement. Second,
      a direct activation and translocation toward the actin patches underneath the
      plasma membrane is observed for endogenous Rac and Cdc42 (but not for RhoA)
      during cell swelling. Finally, transfection of Rat-1 fibroblasts with
      constitutively active RhoA, dominant negative Rac, or dominant negative Cdc42
      abolishes the swelling-induced actin reorganization. Interestingly, application
      of cRGD, a competitor peptide for fibronectin-integrin association, induces
      identical membrane protrusions and changes in the F-actin cytoskeleton that are
      also inhibited by C. difficile toxin B and dominant negative Rac or Cdc42.
      Moreover, cRGD also induces a redistribution of endogenous Rac and Cdc42 to the
      newly formed submembranous F-actin patches. We therefore conclude that
      hypotonicity and cRGD remodel the F-actin cytoskeleton in Rat-1 fibroblasts in a
      Rac/Cdc42-dependent way.

PMID- 12788693
TI  - A proteasome inhibitor reduces concurrent, sequential, and long-term IL-1 beta-
      and TNF-alpha-induced ECAM expression and adhesion.
AB  - A promising approach for reducing aberrant leukocyte-endothelial adhesion during
      pathological inflammation is to inhibit endothelial cell adhesion molecule (ECAM)
      expression at the transcription level. Several compounds have been shown to
      decrease cytokine-induced upregulation of ECAMs primarily by modulating the
      activity of transcription factors [e.g., nuclear factor-kappa B (NF-kappa B)].
      The majority of the in vitro studies have focused on the effect of transcription
      inhibitors on endothelial cells exposed to a single cytokine [primarily tumor
      necrosis factor-alpha (TNF-alpha)] for a relatively short period of time
      (primarily 4-6 h). However, in the in vivo setting, multiple cytokines [e.g.,
      interleukin-1 beta (IL-1 beta) and TNF-alpha] may be present for extended periods
      of time. Thus we studied the effects of a transcription inhibitor, the proteasome
      inhibitor lactacystin, on ECAM expression and myeloid (HL60) cell adhesion to
      human umbilical vein endothelial cells (HUVEC) activated by concurrent,
      sequential, and long-term (24 h) treatment with IL-1 beta and TNF-alpha. We show,
      for the first time, that lactacystin inhibits 1) 4-h concurrent IL-1 beta- and
      TNF-alpha-induced expression of E-selectin, VCAM-1, ICAM-1, and HL60 cell
      adhesion to HUVEC; 2) 4-h TNF-alpha-induced expression of E-selectin, VCAM-1, and
      HL60 cell adhesion to HUVEC that have become desensitized to IL-1 beta
      activation; 3) 24-h TNF-alpha-induced expression of E-selectin and VCAM-1 but not
      ICAM-1; and 4) 24-h TNF-alpha-induced HL60 cell adhesion to HUVEC. Combined, our
      results demonstrate that a proteasome inhibitor can reduce concurrent,
      sequential, and long-term IL-1 beta- and TNF-alpha-induced ECAM expression and
      myeloid cell adhesion.

PMID- 12788694
TI  - Key role of PLC-gamma in EGF protection of epithelial barrier against iNOS
      upregulation and F-actin nitration and disassembly.
AB  - Upregulation of inducible nitric oxide synthase (iNOS) is key to oxidant-induced
      disruption of intestinal (Caco-2) monolayer barrier, and EGF protects against
      this disruption by stabilizing the cytoskeleton. PLC-gamma appears to be
      essential for monolayer integrity. We thus hypothesized that PLC-gamma activation
      is essential in EGF protection against iNOS upregulation and the consequent
      cytoskeletal oxidation and disarray and monolayer disruption. Intestinal cells
      were transfected to stably overexpress PLC-gamma or to inhibit its activation and
      were then pretreated with EGF +/- oxidant (H2O2). Wild-type (WT) intestinal cells
      were treated similarly. Relative to WT monolayers exposed to oxidant,
      pretreatment with EGF protected monolayers by: increasing native PLC-gamma
      activity; decreasing six iNOS-related variables (iNOS activity/protein, NO
      levels, oxidative stress, actin oxidation/nitration); increasing stable F-actin;
      maintaining actin stability; and enhancing barrier integrity. Relative to WT
      cells exposed to oxidant, transfected monolayers overexpressing PLC-gamma (+2.3
      fold) were protected, as indicated by decreases in all measures of iNOS-driven
      pathway and enhanced actin and barrier integrity. Overexpression-induced
      inhibition of iNOS was potentiated by low doses of EGF. Stable inhibition of PLC
      gamma prevented all measures of EGF protection against iNOS upregulation. We
      conclude that 1) EGF protects against oxidative stress disruption of intestinal
      barrier by stabilizing F-Actin, largely through the activation of PLC-gamma and
      downregulation of iNOS pathway; 2) activation of PLC-gamma is by itself essential
      for cellular protection against oxidative stress of iNOS; and 3) the ability to
      suppress iNOS-driven reactions and cytoskeletal oxidation and disassembly is a
      novel mechanism not previously attributed to the PLC family of isoforms.

PMID- 12788695
TI  - Role for phosphoinositide 3-kinase in Fc gamma RIIA-induced platelet shape
      change.
AB  - Platelets transform from disks to irregular spheres, grow filopodia, form
      ruffles, and spread on surfaces coated with anti-Fc gamma RIIA antibody. Fc gamma
      RIIA cross-linking leads to a tenfold increase in actin filament barbed end
      exposure and robust actin assembly. Activation of the small GTPases Rac and Cdc42
      follows Fc gamma RIIA cross-linking. Shape change, actin filament barbed end
      exposure, and quantifiable actin assembly require phosphoinositide 3-kinase (PI3
      kinase) activity and a rise in intracellular calcium. PI3-kinase inhibition
      blocks activation of Rac, but not of Cdc42, and diminishes the association of
      Arp2/3 complex and CapZ with polymerized actin. Furthermore, addition of
      constitutively active D-3 phosphorylated polyphosphoinositides or recombinant PI3
      kinase subunits to octylglucoside-permeabilized platelets elicits actin filament
      barbed end exposure by releasing gelsolin and CapZ from the cytoskeleton. Our
      findings place PI3-kinase activity upstream of Rac, gelsolin, and Arp2/3 complex
      activation induced by Fc gamma RIIA and clearly distinguish the Fc gamma RIIA
      signaling pathway to actin filament assembly from the thrombin receptor protease
      activated receptor (PAR)-1 pathway.

PMID- 12788696
TI  - Isolation and characterization of NaCl-sensitive mutants of Caulobacter
      crescentus.
AB  - An attempt to characterize Caulobacter crescentus genes important for the
      response to high concentrations of NaCl was initiated by the isolation of mutants
      defective in survival in the presence of 85 mM NaCl. A transposon Tn5 library was
      screened, and five strains which contained different genes disrupted by the
      transposon were isolated. Three of the mutants had the Tn5 in genes involved in
      lipopolysaccharide biosynthesis, one had the Tn5 in the nhaA gene, which encodes
      a Na(+)/H(+) antiporter, and one had the Tn5 in the ppiD gene, which encodes a
      peptidyl-prolyl cis-trans isomerase. All the mutant strains showed severe growth
      arrest in the presence of 85 mM NaCl, but only the nhaA mutant showed decreased
      viability under these conditions. All the mutants except the nhaA mutant showed a
      slightly reduced viability in the presence of 40 mM KCl, but all the strains
      showed a more severe reduction in viability in the presence of 150 mM sucrose,
      suggesting that they are defective in responding to osmotic shock. The promoter
      regions of each disrupted gene were cloned in lacZ reporter vectors, and the
      pattern of expression in response to NaCl and sucrose was determined; this showed
      that both agents induced ppiD and nhaA gene expression but did not induce the
      other genes. Furthermore, the ppiD gene was not induced by heat shock, indicating
      that it does not belong to the sigma(32) regulon, as opposed to what was observed
      for its Escherichia coli homolog.

PMID- 12788697
TI  - Dynamics of microbial communities on marine snow aggregates: colonization,
      growth, detachment, and grazing mortality of attached bacteria.
AB  - We studied the dynamics of microbial communities attached to model aggregates (4
      mm-diameter agar spheres) and the component processes of colonization,
      detachment, growth, and grazing mortality. Agar spheres incubated in raw seawater
      were rapidly colonized by bacteria, followed by flagellates and ciliates.
      Colonization can be described as a diffusion process, and encounter volume rates
      were estimated at about 0.01 and 0.1 cm(3) h(-1) for bacteria and flagellates,
      respectively. After initial colonization, the abundances of flagellates and
      ciliates remained approximately constant at 10(3) to 10(4) and approximately
      10(2) cells sphere(-1), respectively, whereas bacterial populations increased at
      a declining rate to >10(7) cells sphere(-1). Attached microorganisms initially
      detached at high specific rates of approximately 10(-2) min(-1), but the bacteria
      gradually became irreversibly attached to the spheres. Bacterial growth (0 to 2
      day(-1)) was density dependent and declined hyperbolically when cell density
      exceeded a threshold. Bacterivorous flagellates grazed on the sphere surface at
      an average saturated rate of 15 bacteria flagellate(-1) h(-1). At low bacterial
      densities, the flagellate surface clearance rate was approximately 5 x 10(-7)
      cm(2) min(-1), but it declined hyperbolically with increasing bacterial density.
      Using the experimentally estimated process rates and integrating the component
      processes in a simple model reproduces the main features of the observed
      microbial population dynamics. Differences between observed and predicted
      population dynamics suggest, however, that other factors, e.g., antagonistic
      interactions between bacteria, are of importance in shaping marine snow microbial
      communities.

PMID- 12788698
TI  - Identification and characterization of coenzyme B12-dependent glycerol
      dehydratase- and diol dehydratase-encoding genes from metagenomic DNA libraries
      derived from enrichment cultures.
AB  - To isolate genes encoding coenzyme B(12)-dependent glycerol and diol
      dehydratases, metagenomic libraries from three different environmental samples
      were constructed after allowing growth of the dehydratase-containing
      microorganisms present for 48 h with glycerol under anaerobic conditions. The
      libraries were searched for the targeted genes by an activity screen, which was
      based on complementation of a constructed dehydratase-negative Escherichia coli
      strain. In this way, two positive E. coli clones out of 560,000 tested clones
      were obtained. In addition, screening was performed by colony hybridization with
      dehydratase-specific DNA fragments as probes. The screening of 158,000 E. coli
      clones by this method yielded five positive clones. Two of the plasmids (pAK6 and
      pAK8) recovered from the seven positive clones contained genes identical to those
      encoding the glycerol dehydratase of Citrobacter freundii and were not studied
      further. The remaining five plasmids (pAK2 to -5 and pAK7) contained two complete
      and three incomplete dehydratase-encoding gene regions, which were similar to the
      corresponding regions of enteric bacteria. Three (pAK2, -3, and -7) coded for
      glycerol dehydratases and two (pAK4 and -5) coded for diol dehydratases. We were
      able to perform high-level production and purification of three of these
      dehydratases. The glycerol dehydratases purified from E. coli Bl21/pAK2.1 and E.
      coli Bl21/pAK7.1 and the complemented hybrid diol dehydratase purified from E.
      coli Bl21/pAK5.1 were subject to suicide inactivation by glycerol and were cross
      reactivated by the reactivation factor (DhaFG) for the glycerol dehydratase of C.
      freundii. The activities of the three environmentally derived dehydratases and
      that of glycerol dehydratase of C. freundii with glycerol or 1,2-propanediol as
      the substrate were inhibited in the presence of the glycerol fermentation product
      1,3-propanediol. Taking the catalytic efficiency, stability against inactivation
      by glycerol, and inhibition by 1,3-propanediol into account, the hybrid diol
      dehydratase produced by E. coli Bl21/pAK5.1 exhibited the best properties of all
      tested enzymes for application in the biotechnological production of 1,3
      propanediol.

PMID- 12788699
TI  - CodY-regulated aminotransferases AraT and BcaT play a major role in the growth of
      Lactococcus lactis in milk by regulating the intracellular pool of amino acids.
AB  - Aminotransferases, which catalyze the last step of biosynthesis of most amino
      acids and the first step of their catabolism, may be involved in the growth of
      Lactococcus lactis in milk. Previously, we isolated two aminotransferases from L.
      lactis, AraT and BcaT, which are responsible for the transamination of aromatic
      amino acids, branched-chain amino acids, and methionine. In this study, we
      demonstrated that double inactivation of AraT and BcaT strongly reduced the
      growth of L. lactis in milk. Supplementation of milk with amino acids and keto
      acids that are substrates of both aminotransferases did not improve the growth of
      the double mutant. On the contrary, supplementation of milk with isoleucine or a
      dipeptide containing isoleucine almost totally inhibited the growth of the double
      mutant, while it did not affect or only slightly affected the growth of the wild
      type strain. These results suggest that AraT and BcaT play a major role in the
      growth of L. lactis in milk by degrading the intracellular excess isoleucine,
      which is responsible for the growth inhibition. The growth inhibition by
      isoleucine is likely to be due to CodY repression of the proteolytic system,
      which is necessary for maximal growth of L. lactis in milk, since the growth of
      the CodY mutant was not affected by addition of isoleucine to milk. Moreover, we
      demonstrated that AraT and BcaT are part of the CodY regulon and therefore are
      regulated by nutritional factors, such as the carbohydrate and nitrogen sources.

PMID- 12788700
TI  - Increased production of folate by metabolic engineering of Lactococcus lactis.
AB  - The dairy starter bacterium Lactococcus lactis is able to synthesize folate and
      accumulates large amounts of folate, predominantly in the polyglutamyl form. Only
      small amounts of the produced folate are released in the extracellular medium.
      Five genes involved in folate biosynthesis were identified in a folate gene
      cluster in L. lactis MG1363: folA, folB, folKE, folP, and folC. The gene folKE
      encodes the biprotein 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine
      pyrophosphokinase and GTP cyclohydrolase I. The overexpression of folKE in L.
      lactis was found to increase the extracellular folate production almost 10-fold,
      while the total folate production increased almost 3-fold. The controlled
      combined overexpression of folKE and folC, encoding polyglutamyl folate
      synthetase, increased the retention of folate in the cell. The cloning and
      overexpression of folA, encoding dihydrofolate reductase, decreased the folate
      production twofold, suggesting a feedback inhibition of reduced folates on folate
      biosynthesis.

PMID- 12788701
TI  - Mycotoxigenic Fusarium and deoxynivalenol production repress chitinase gene
      expression in the biocontrol agent Trichoderma atroviride P1.
AB  - Mycotoxin contamination associated with head blight of wheat and other grains
      caused by Fusarium culmorum and F. graminearum is a chronic threat to crop,
      human, and animal health throughout the world. One of the most important toxins
      in terms of human exposure is deoxynivalenol (DON) (formerly called vomitoxin),
      an inhibitor of protein synthesis with a broad spectrum of toxigenicity against
      animals. Certain Fusarium toxins have additional antimicrobial activity, and the
      phytotoxin fusaric acid has recently been shown to modulate fungus-bacterium
      interactions that affect plant health (Duffy and Defago, Phytopathology 87:1250
      1257, 1997). The potential impact of DON on Fusarium competition with other
      microorganisms has not been described previously. Any competitive advantage
      conferred by DON would complicate efforts to control Fusarium during its
      saprophytic growth on crop residues that are left after harvest and constitute
      the primary inoculum reservoir for outbreaks in subsequent plantings. We examined
      the effect of the DON mycotoxin on ecological interactions between pathogenic
      Fusarium and Trichoderma atroviride strain P1, a competitor fungus with
      biocontrol activity against a wide range of plant diseases. Expression of the
      Trichoderma chitinase genes, ech42 and nag1, which contribute to biocontrol
      activity, was monitored in vitro and on crop residues of two maize cultivars by
      using goxA reporter gene fusions. We found that DON-producing F. culmorum and F.
      graminearum strains repressed expression of nag1-gox. DON-negative wild-type
      Fusarium strains and a DON-negative mutant with an insertional disruption in the
      tricothecene biosynthetic gene, tri5, had no effect on antagonist gene
      expression. The role of DON as the principal repressor above other pathogen
      factors was confirmed. Exposure of Trichoderma to synthetic DON or to a non-DON
      producing Fusarium mutant resulted in the same level of nag1-gox repression as
      the level observed with DON-producing FUSARIUM: DON repression was specific for
      nag1-gox and had no effect, either positive or negative, on expression of another
      key chitinase gene, ech42. This is the first demonstration that a target pathogen
      down-regulates genes in a fungal biocontrol agent, and our results provide
      evidence that mycotoxins have a novel ecological function as factors in Fusarium
      competitiveness.

PMID- 12788702
TI  - Characterization of hydrocarbon-degrading microbial populations in contaminated
      and pristine Alpine soils.
AB  - Biodegradation of petroleum hydrocarbons in cold environments, including Alpine
      soils, is a result of indigenous cold-adapted microorganisms able to degrade
      these contaminants. In the present study, the prevalence of seven genotypes
      involved in the degradation of n-alkanes (Pseudomonas putida GPo1 alkB;
      Acinetobacter spp. alkM; Rhodococcus spp. alkB1, and Rhodococcus spp. alkB2),
      aromatic hydrocarbons (P. putida xylE), and polycyclic aromatic hydrocarbons (P.
      putida ndoB and Mycobacterium sp. strain PYR-1 nidA) was determined in 12 oil
      contaminated (428 to 30,644 mg of total petroleum hydrocarbons [TPH]/kg of soil)
      and 8 pristine Alpine soils from Tyrol (Austria) by PCR hybridization analyses of
      total soil community DNA, using oligonucleotide primers and DNA probes specific
      for each genotype. The soils investigated were also analyzed for various
      physical, chemical, and microbiological parameters, and statistical correlations
      between all parameters were determined. Genotypes containing genes from gram
      negative bacteria (P. putida alkB, xylE, and ndoB and Acinetobacter alkM) were
      detected to a significantly higher percentage in the contaminated (50 to 75%)
      than in the pristine (0 to 12.5%) soils, indicating that these organisms had been
      enriched in soils following contamination. There was a highly significant
      positive correlation (P < 0.001) between the level of contamination and the
      number of genotypes containing genes from P. putida and Acinetobacter sp. but no
      significant correlation between the TPH content and the number of genotypes
      containing genes from gram-positive bacteria (Rhodococcus alkB1 and alkB2 and
      Mycobacterium nidA). These genotypes were detected at a high frequency in both
      contaminated (41.7 to 75%) and pristine (37.5 to 50%) soils, indicating that they
      are already present in substantial numbers before a contamination event. No
      correlation was found between the prevalence of hydrocarbon-degradative genotypes
      and biological activities (respiration, fluorescein diacetate hydrolysis, lipase
      activity) or numbers of culturable hydrocarbon-degrading soil microorganisms;
      there also was no correlation between the numbers of hydrocarbon degraders and
      the contamination level. The measured biological activities showed significant
      positive correlation with each other, with the organic matter content, and
      partially with the TPH content and a significant negative correlation with the
      soil dry-mass content (P < 0.05 to 0.001).

PMID- 12788703
TI  - Genes involved in the biosynthesis of photosynthetic pigments in the purple
      sulfur photosynthetic bacterium Thiocapsa roseopersicina.
AB  - A pigment mutant strain of the purple sulfur photosynthetic bacterium Thiocapsa
      roseopersicina BBS was isolated by plasposon mutagenesis. Nineteen open reading
      frame, most of which are thought to be genes involved in the biosynthesis of
      carotenoids, bacteriochlorophyll, and the photosynthetic reaction center, were
      identified surrounding the plasposon in a 22-kb-long chromosomal locus. The
      general arrangement of the photosynthetic genes was similar to that in other
      purple photosynthetic bacteria; however, the locations of a few genes occurring
      in this region were unusual. Most of the gene products showed the highest
      similarity to the corresponding proteins in Rubrivivax gelatinosus. The plasposon
      was inserted into the crtD gene, likely inactivating crtC as well, and the
      carotenoid composition of the mutant strain corresponded to the aborted
      spirilloxanthin pathway. Homologous and heterologous complementation experiments
      indicated a conserved function of CrtC and CrtD in the purple photosynthetic
      bacteria. The crtDC and crtE genes were shown to be regulated by oxygen, and a
      role of CrtJ in aerobic repression was suggested.

PMID- 12788704
TI  - Characterization of the microbial community in indoor environments: a chemical
      analytical approach.
AB  - An integrated procedure is presented whereby gas chromatography-ion trap mass
      spectrometry is used to determine chemical markers of gram-negative bacterial
      lipopolysaccharide (3-hydroxy fatty acids with 10 to 18 carbon atoms), gram
      positive bacteria (branched-chain fatty acids with 15 and 17 carbon atoms),
      bacterial peptidoglycan (muramic acid), and fungal biomass (ergosterol) in
      samples of settled house dust. A hydrolysate of (13)C-labeled cyanobacterial
      cells is used as an internal standard for the first three markers. These analyses
      require two dust samples, one for 3-OH fatty acids, branched-chain fatty acids,
      and muramic acid and another for ergosterol. The method may be used to
      characterize microbial communities in environmental samples.

PMID- 12788705
TI  - Repeated introduction of genetically modified Pseudomonas putida WCS358r without
      intensified effects on the indigenous microflora of field-grown wheat.
AB  - To investigate the impact of genetically modified, antibiotic-producing
      rhizobacteria on the indigenous microbial community, Pseudomonas putida WCS358r
      and two transgenic derivatives were introduced as a seed coating into the
      rhizosphere of wheat in two consecutive years (1999 and 2000) in the same field
      plots. The two genetically modified microorganisms (GMMs), WCS358r::phz and
      WCS358r::phl, constitutively produced phenazine-1-carboxylic acid (PCA) and 2,4
      diacetylphloroglucinol (DAPG), respectively. The level of introduced bacteria in
      all treatments decreased from 10(7) CFU per g of roots soon after sowing to less
      than 10(2) CFU per g after harvest 132 days after sowing. The phz and phl genes
      remained stable in the chromosome of WCS358r. The amount of PCA produced in the
      wheat rhizosphere by WCS358r::phz was about 40 ng/g of roots after the first
      application in 1999. The DAPG-producing GMMs caused a transient shift in the
      indigenous bacterial and fungal microflora in 1999, as determined by amplified
      ribosomal DNA restriction analysis. However, after the second application of the
      GMMs in 2000, no shifts in the bacterial or fungal microflora were detected. To
      evaluate the importance of the effects induced by the GMMs, these effects were
      compared with those induced by crop rotation by planting wheat in 1999 followed
      by potatoes in 2000. No effect of rotation on the microbial community structure
      was detected. In 2000 all bacteria had a positive effect on plant growth,
      supposedly due to suppression of deleterious microorganisms. Our research
      suggests that the natural variability of microbial communities can surpass the
      effects of GMMs.

PMID- 12788706
TI  - Growth of hyperthermophilic archaeon Pyrococcus furiosus on chitin involves two
      family 18 chitinases.
AB  - Pyrococcus furiosus was found to grow on chitin, adding this polysacharide to the
      inventory of carbohydrates utilized by this hyperthermophilic archaeon.
      Accordingly, two open reading frames (chiA [Pf1234] and chiB [Pf1233]) were
      identified in the genome of P. furiosus, which encodes chitinases with sequence
      similarity to proteins from the glycosyl hydrolase family 18 in less-thermophilic
      organisms. Both enzymes contain multiple domains that consist of at least one
      binding domain and one catalytic domain. ChiA (ca. 39 kDa) contains a putative
      signal peptide, as well as a binding domain (ChiA(BD)), that is related to
      binding domains associated with several previously studied bacterial chitinases.
      chiB, separated by 37 nucleotides from chiA and in the same orientation, encodes
      a polypeptide with two different proline-threonine-rich linker regions (6 and 3
      kDa) flanking a chitin-binding domain (ChiB(BD) [11 kDa]), followed by a
      catalytic domain (ChiB(cat) [35 kDa]). No apparent signal peptide is encoded
      within chiB. The two chitinases share little sequence homology to each other,
      except in the catalytic region, where both have the catalytic glutamic acid
      residue that is conserved in all family 18 bacterial chitinases. The genes
      encoding ChiA, without its signal peptide, and ChiB were cloned and expressed in
      Escherichia coli. ChiA exhibited no detectable activity toward chitooligomers
      smaller than chitotetraose, indicating that the enzyme is an endochitinase.
      Kinetic studies showed that ChiB followed Michaelis-Menten kinetics toward
      chitotriose, although substrate inhibition was observed for larger
      chitooligomers. Hydrolysis patterns on chitooligosaccharides indicated that ChiB
      is a chitobiosidase, processively cleaving off chitobiose from the nonreducing
      end of chitin or other chitooligomers. Synergistic activity was noted for the two
      chitinases on colloidal chitin, indicating that these two enzymes work together
      to recruit chitin-based substrates for P. furiosus growth. This was supported by
      the observed growth on chitin as the sole carbohydrate source in sulfur-free
      media.

PMID- 12788707
TI  - Ammonia-oxidizing bacteria along meadow-to-forest transects in the Oregon Cascade
      Mountains.
AB  - Although nitrification has been well studied in coniferous forests of Western
      North America, communities of NH(3)-oxidizing bacteria in these forests have not
      been characterized. Studies were conducted along meadow-to-forest transects at
      two sites (Lookout and Carpenter) in the H. J. Andrews Experimental Forest,
      located in the Cascade Mountains of Oregon. Soil samples taken at 10- or 20-m
      intervals along the transects showed that several soil properties, including net
      nitrogen mineralization and nitrification potential rates changed significantly
      between vegetation zones. Nonetheless, terminal restriction fragment length
      polymorphism (T-RFLP) analysis of the PCR-amplified NH(3) monooxygenase subunit A
      gene (amoA) showed the same DNA fragments (TaqI [283 bp], CfoI [66 bp], and AluI
      [392 bp]) to dominate >/=45 of 47 soil samples recovered from both sites. Two
      fragments (491-bp AluI [AluI491] and CfoI135) were found more frequently in
      meadow and transition zone soil samples than in forest samples at both sites. At
      the Lookout site the combination AluI491-CfoI135 was found primarily in meadow
      samples expressing the highest N mineralization rates. Four unique amoA sequences
      were identified among 15 isolates recovered into pure culture from various
      transect locations. Six isolates possessed the most common T-RFLP amoA
      fingerprint of the soil samples (TaqI283-AluI392-CfoI66), and their amoA
      sequences shared 99.8% similarity with a cultured species, Nitrosospira sp.
      strain Ka4 (cluster 4). The other three amoA sequences were most similar to
      sequences of Nitrosospira sp. strain Nsp1 and Nitrosospira briensis (cluster 3).
      16S ribosomal DNA sequence analysis confirmed the affiliation of these isolates
      with Nitrosospira clusters 3 and 4. Two amoA clone sequences matched T-RFLP
      fingerprints found in soil, but they were not found among the isolates.

PMID- 12788708
TI  - Identification of Listeria monocytogenes genes involved in salt and alkaline-pH
      tolerance.
AB  - The capacity of Listeria monocytogenes to tolerate salt and alkaline stresses is
      of particular importance, as this pathogen is often exposed to such environments
      during food processing and food preservation. We screened a library of Tn917-lacZ
      insertional mutants in order to identify genes involved in salt and/or alkaline
      tolerance. We isolated six mutants sensitive to salt stress and 12 mutants
      sensitive to salt and alkaline stresses. The position of the insertion of the
      transposon was located in 15 of these mutants. In six mutants the transposon was
      inserted in intergenic regions, and in nine mutants it was inserted in genes.
      Most of the genes have unknown functions, but sequence comparisons indicated that
      they encode putative transporters.

PMID- 12788709
TI  - Vector systems allowing efficient autonomous or integrative gene cloning in
      Micromonospora sp. strain 40027.
AB  - Vector systems allowing autonomous or site-specific integrative gene cloning were
      developed for Micromonospora sp. strain 40027, a producer of the antibiotic
      fortimicin A. The autonomous system depends on the discovery of a low-copy
      number, self-transmissible covalently closed circular plasmid, pJTU112 (ca. 14.1
      kb), which was shown to be present in the progenitor strain in both integrated
      and autonomous states. The copy numbers of both wild-type pJTU112 and three
      derivatives of it can be amplified at least sixfold by addition of streptomycin
      to the culture medium. The integrative system was developed by the use of a
      pBR322-derived Escherichia coli plasmid vector, pSET152, mediated by the attP
      site of the Streptomyces phage PhiC31. Both vectors can be transferred by
      conjugation from E. coli into Micromonospora sp. strain 40027. The heterologous
      cloning and expression of the dnd gene cluster originating from Streptomyces
      lividans 1326 into Micromonospora sp. strain 40027 demonstrated the use of the
      two systems.

PMID- 12788710
TI  - Aerobic denitrifying bacteria that produce low levels of nitrous oxide.
AB  - Most denitrifiers produce nitrous oxide (N(2)O) instead of dinitrogen (N(2))
      under aerobic conditions. We isolated and characterized novel aerobic
      denitrifiers that produce low levels of N(2)O under aerobic conditions. We
      monitored the denitrification activities of two of the isolates, strains TR2 and
      K50, in batch and continuous cultures. Both strains reduced nitrate (NO(3)(-)) to
      N(2) at rates of 0.9 and 0.03 micro mol min(-1) unit of optical density at 540
      nm(-1) at dissolved oxygen (O(2)) (DO) concentrations of 39 and 38 micro mol
      liter(-1), respectively. At the same DO level, the typical denitrifier
      Pseudomonas stutzeri and the previously described aerobic denitrifier Paracoccus
      denitrificans did not produce N(2) but evolved more than 10-fold more N(2)O than
      strains TR2 and K50 evolved. The isolates denitrified NO(3)(-) with concomitant
      consumption of O(2). These results indicated that strains TR2 and K50 are aerobic
      denitrifiers. These two isolates were taxonomically placed in the beta subclass
      of the class Proteobacteria and were identified as P. stutzeri TR2 and
      Pseudomonas sp. strain K50. These strains should be useful for future
      investigations of the mechanisms of denitrifying bacteria that regulate N(2)O
      emission, the single-stage process for nitrogen removal, and microbial N(2)O
      emission into the ecosystem.

PMID- 12788711
TI  - A multiplex reverse transcription-PCR method for detection of human enteric
      viruses in groundwater.
AB  - Untreated groundwater is responsible for about half of the waterborne disease
      outbreaks in the United States. Human enteric viruses are thought to be leading
      etiological agents of many of these outbreaks, but there is relatively little
      information on the types and levels of viruses found in groundwater. To address
      this problem, monthly samples from 29 groundwater sites were analyzed for 1 year
      for enteroviruses, hepatitis A virus, Norwalk virus, reoviruses, and rotaviruses
      by multiplex reverse transcription-PCR (RT-PCR). A procedure with which to remove
      environmental RT-PCR inhibitors from groundwater samples was developed. The
      procedure allowed an average of 71 liters of the original groundwater to be
      assayed per RT-PCR, with an average virus recovery rate of 74%, based on seeded
      samples. Human enteric viruses were detected in 16% of the groundwater samples
      analyzed, with reoviruses being the most frequently detected virus group.

PMID- 12788712
TI  - Identification of intermediate and branch metabolites resulting from
      biotransformation of 2-benzoxazolinone by Fusarium verticillioides.
AB  - Detoxification of the maize (Zea mays) antimicrobial compound 2-benzoxazolinone
      by the fungal endophyte Fusarium verticillioides involves two genetic loci, FDB1
      and FDB2, and results in the formation of N-(2-hydroxyphenyl)malonamic acid.
      Intermediate and branch metabolites were previously suggested to be part of the
      biotransformation pathway. Evidence is presented here in support of 2-aminophenol
      as the intermediate metabolite and 2-acetamidophenol as the branch metabolite,
      which was previously designated as BOA-X. Overall, 2-benzoxazolinone metabolism
      involves hydrolysis (FDB1) to produce 2-aminophenol, which is then modified
      (FDB2) by addition of a malonyl group to produce N-(2-hydroxyphenyl)malonamic
      acid. If the modification is prevented due to genetic mutation (fbd2), then 2
      acetamidophenol may accumulate as a result of addition of an acetyl group to 2
      aminophenol. This study resolves the overall chemistry of the 2-benzoxazolinone
      detoxification pathway, and we hypothesize that biotransformation of the related
      antimicrobial 6-methoxy-2-benzoxazolinone to produce N-(2-hydroxy-4
      methoxyphenyl)malonamic acid also occurs via the same enzymatic modifications.
      Detoxification of these antimicrobials by F. verticillioides apparently is not a
      major virulence factor but may enhance the ecological fitness of the fungus
      during colonization of maize stubble and field debris.

PMID- 12788713
TI  - Intraspecific diversity of Vibrio vulnificus in Galveston Bay water and oysters
      as determined by randomly amplified polymorphic DNA PCR.
AB  - Randomly amplified polymorphic DNA (RAPD) PCR was used to analyze the temporal
      and spatial intraspecific diversity of 208 Vibrio vulnificus strains isolated
      from Galveston Bay water and oysters at five different sites between June 2000
      and June 2001. V. vulnificus was not detected during the winter months (December
      through February). The densities of V. vulnificus in water and oysters were
      positively correlated with water temperature. Cluster analysis of RAPD PCR
      profiles of the 208 V. vulnificus isolates revealed a high level of intraspecific
      diversity among the strains. No correlation was found between the intraspecific
      diversity among the isolates and sampling site or source of isolation. After not
      being detected during the winter months, the genetic diversity of V. vulnificus
      strains first isolated in March was 0.9167. Beginning in April, a higher level of
      intraspecific diversity (0.9933) and a major shift in population structure were
      observed among V. vulnificus isolates. These results suggest that a great genetic
      diversity of V. vulnificus strains exists in Galveston Bay water and oysters and
      that the population structure of this species is linked to changes in
      environmental conditions, especially temperature.

PMID- 12788714
TI  - Enhanced mercury biosorption by bacterial cells with surface-displayed MerR.
AB  - The metalloregulatory protein MerR, which exhibits high affinity and selectivity
      toward mercury, was exploited for the construction of microbial biosorbents
      specific for mercury removal. Whole-cell sorbents were constructed with MerR
      genetically engineered onto the surface of Escherichia coli cells by using an ice
      nucleation protein anchor. The presence of surface-exposed MerR on the engineered
      strains enabled sixfold-higher Hg(2+) biosorption than that found in the wild
      type JM109 cells. Hg(2+) binding via MerR was very specific, with no observable
      decline even in the presence of 100-fold excess Cd(2+) and Zn(2+). The Hg(2+)
      binding property of the whole-cell sorbents was also insensitive to different
      ionic strengths, pHs, and the presence of metal chelators. Since
      metalloregulatory proteins are currently available for a wide variety of toxic
      heavy metals, our results suggest that microbial biosorbents overexpressing
      metalloregulatory proteins may be used similarly for the cleanup of other
      important heavy metals.

PMID- 12788715
TI  - Analysis of the sulfate-reducing bacterial and methanogenic archaeal populations
      in contrasting Antarctic sediments.
AB  - The distribution and activity of communities of sulfate-reducing bacteria (SRB)
      and methanogenic archaea in two contrasting Antarctic sediments were
      investigated. Methanogenesis dominated in freshwater Lake Heywood, while sulfate
      reduction dominated in marine Shallow Bay. Slurry experiments indicated that 90%
      of the methanogenesis in Lake Heywood was acetoclastic. This finding was
      supported by the limited diversity of clones detected in a Lake Heywood archaeal
      clone library, in which most clones were closely related to the obligate acetate
      utilizing Methanosaeta concilii. The Shallow Bay archaeal clone library contained
      clones related to the C(1)-utilizing Methanolobus and Methanococcoides and the
      H(2)-utilizing Methanogenium: Oligonucleotide probing of RNA extracted directly
      from sediment indicated that archaea represented 34% of the total prokaryotic
      signal in Lake Heywood and that Methanosaeta was a major component (13.2%) of
      this signal. Archaea represented only 0.2% of the total prokaryotic signal in RNA
      extracted from Shallow Bay sediments. In the Shallow Bay bacterial clone library,
      10.3% of the clones were SRB-like, related to Desulfotalea/Desulforhopalus,
      Desulfofaba, Desulfosarcina, and Desulfobacter as well as to the sulfur and metal
      oxidizers comprising the Desulfuromonas cluster. Oligonucleotide probes for
      specific SRB clusters indicated that SRB represented 14.7% of the total
      prokaryotic signal, with Desulfotalea/Desulforhopalus being the dominant SRB
      group (10.7% of the total prokaryotic signal) in the Shallow Bay sediments; these
      results support previous results obtained for Arctic sediments. Methanosaeta and
      Desulfotalea/Desulforhopalus appear to be important in Lake Heywood and Shallow
      Bay, respectively, and may be globally important in permanently low-temperature
      sediments.

PMID- 12788716
TI  - Bacteriophage ecology in commercial sauerkraut fermentations.
AB  - Knowledge of bacteriophage ecology in vegetable fermentations is essential for
      developing phage control strategies for consistent and high quality of fermented
      vegetable products. The ecology of phages infecting lactic acid bacteria (LAB) in
      commercial sauerkraut fermentations was investigated. Brine samples were taken
      from four commercial sauerkraut fermentation tanks over a 60- or 100-day period
      in 2000 and 2001. A total of 171 phage isolates, including at least 26 distinct
      phages, were obtained. In addition, 28 distinct host strains were isolated and
      identified as LAB by restriction analysis of the intergenic transcribed spacer
      region and 16S rRNA sequence analysis. These host strains included Leuconostoc,
      Weissella, and Lactobacillus species. It was found that there were two phage-host
      systems in the fermentations corresponding to the population shift from
      heterofermentative to homofermentative LAB between 3 and 7 days after the start
      of the fermentations. The data suggested that phages may play an important role
      in the microbial ecology and succession of LAB species in vegetable
      fermentations. Eight phage isolates, which were independently obtained two or
      more times, were further characterized. They belonged to the family Myoviridae or
      Siphoviridae and showed distinct host ranges and DNA fingerprints. Two of the
      phage isolates were found to be capable of infecting two Lactobacillus species.
      The results from this study demonstrated for the first time the complex phage
      ecology present in commercial sauerkraut fermentations, providing new insights
      into the bioprocess of vegetable fermentations.

PMID- 12788717
TI  - Population genetics of Vibrio vulnificus: identification of two divisions and a
      distinct eel-pathogenic clone.
AB  - Genetic relationships among 62 Vibrio vulnificus strains of different
      geographical and host origins were analyzed by multilocus enzyme electrophoresis
      (MLEE), random amplification of polymorphic DNA (RAPD), and sequence analyses of
      the recA and glnA genes. Out of 15 genetic loci analyzed by MLEE, 11 were
      polymorphic. Cluster analysis identified 43 distinct electrophoretic types (ETs)
      separating the V. vulnificus population into two divisions (divisions I and II).
      One ET (ET 35) included all indole-negative isolates from diseased eels worldwide
      (biotype 2). A second ET (ET 2) marked all of the strains from Israel isolated
      from patients who handled St. Peter's fish (biotype 3). RAPD analysis of the 62
      V. vulnificus isolates identified 26 different profiles separated into two
      divisions as well. In general, this subdivision was comparable (but not
      identical) to that observed by MLEE. Phylogenetic analysis of 543 bp of the recA
      gene and of 402 bp of the glnA gene also separated the V. vulnificus population
      into two major divisions in a manner similar to that by MLEE and RAPD. Sequence
      data again indicated the overall subdivision of the V. vulnificus population into
      different biotypes. In particular, indole-negative eel-pathogenic isolates
      (biotype 2) on one hand and the Israeli isolates (biotype 3) on the other tended
      to cluster together in both gene trees. None of the methods showed an association
      between distinct clones and human clinical manifestations. Furthermore, except
      for the Israeli strains, only minor clusters comprising geographically related
      isolates were observed. In conclusion, all three approaches (MLEE, RAPD, and DNA
      sequencing) generated comparable but not always equivalent results. The
      significance of the two divisions (divisions I and II) still remains to be
      clarified, and a reevaluation of the definition of the biotypes is also needed.

PMID- 12788718
TI  - Community analysis of ammonia and nitrite oxidizers during start-up of
      nitritation reactors.
AB  - Partial nitrification of ammonium to nitrite under oxic conditions (nitritation)
      is a critical process for the effective use of alternative nitrogen removal
      technologies from wastewater. Here we investigated the conditions which promote
      establishment of a suitable microbial community for performing nitritation when
      starting from regular sewage sludge. Reactors were operated in duplicate under
      different conditions (pH, temperature, and dilution rate) and were fed with 50 mM
      ammonium either as synthetic medium or as sludge digester supernatant. In all
      cases, stable nitritation could be achieved within 10 to 20 days after
      inoculation. Quantitative in situ hybridization analysis with group-specific
      fluorescent rRNA-targeted oligonucleotides (FISH) in the different reactors
      showed that nitrite-oxidizing bacteria of the genus Nitrospira were only active
      directly after inoculation with sewage sludge (up to 4 days and detectable up to
      10 days). As demonstrated by quantitative FISH and restriction fragment length
      polymorphism (RFLP) analyses of the amoA gene (encoding the active-site subunit
      of the ammonium monooxygenase), the community of ammonia-oxidizing bacteria
      changed within the first 15 to 20 days from a more diverse set of populations
      consisting of members of the Nitrosomonas communis and Nitrosomonas oligotropha
      sublineages and the Nitrosomonas europaea-Nitrosomonas eutropha subgroup in the
      inoculated sludge to a smaller subset in the reactors. Reactors operated at 30
      degrees C and pH 7.5 contained reproducibly homogeneous communities dominated by
      one amoA RFLP type from the N. europaea-N. eutropha group. Duplicate reactors at
      pH 7.0 developed into diverse communities and showed transient population changes
      even within the ammonia oxidizer community. Reactors at pH 7.5 and 25 degrees C
      formed communities that were indistinguishable by the applied FISH probes but
      differing in amoA RFLP types. Communities in reactors fed with sludge digester
      supernatant exhibited a higher diversity and were constantly reinoculated with
      ammonium oxidizers from the supernatant. Therefore, such systems could be
      maintained at a higher dilution rate (0.75 day(-1) compared to 0.2 day(-1) for
      the synthetic wastewater reactors). Despite similar reactor performance with
      respect to chemical parameters, the underlying community structures were
      different, which may have an influence on stability during perturbations.

PMID- 12788719
TI  - Cultivation-dependent and -independent approaches for determining bacterial
      diversity in heavy-metal-contaminated soil.
AB  - In recent years, culture-independent methods have been used in preference to
      traditional isolation techniques for microbial community analysis. However, it is
      questionable whether uncultured organisms from a given sample are important for
      determining the impact of anthropogenic stress on indigenous communities. To
      investigate this, soil samples were taken from a site with patchy metal
      contamination, and the bacterial community structure was assessed with a variety
      of approaches. There were small differences in microscopic epifluorescence
      bacterial counts. Denaturing gradient gel electrophoresis (DGGE) profiles of 16S
      rRNA gene fragments (16S-DGGE) amplified directly from soil samples were highly
      similar. A clone library generated from the most contaminated sample revealed a
      diverse bacterial community, which showed similarities to pristine soil
      communities from other studies. However, the proportion of bacteria from the soil
      samples that were culturable on standard plate-counting media varied between 0.08
      and 2.2%, and these values correlated negatively with metal concentrations. The
      culturable communities from each sample were compared by 16S-DGGE of plate washes
      and by fatty acid profiling of individual isolates. Each approach indicated that
      there were considerable differences between the compositions of the culturable
      communities from each sample. DGGE bands from both culture-based and culture
      independent approaches were sequenced and compared. These data indicated that
      metal contamination did not have a significant effect on the total genetic
      diversity present but affected physiological status, so that the number of
      bacteria capable of responding to laboratory culture and their taxonomic
      distribution were altered. Thus, it appears that plate counts may be a more
      appropriate method for determining the effect of heavy metals on soil bacteria
      than culture-independent approaches.

PMID- 12788720
TI  - Escherichia coli heat shock protein DnaK: production and consequences in terms of
      monitoring cooking.
AB  - Through use of commercially available DnaK proteins and anti-DnaK monoclonal
      antibodies, a competitive enzyme-linked immunosorbent assay was developed to
      quantify this heat shock protein in Escherichia coli ATCC 25922 subjected to
      various heating regimens. For a given process lethality (F(70)(10) of 1, 3, and 5
      min), the intracellular concentration of DnaK in E. coli varied with the heating
      temperature (50 or 55 degrees C). In fact, the highest DnaK concentrations were
      found after treatments at the lower temperature (50 degrees C) applied for a
      longer time. Residual DnaK after heating was found to be necessary for cell
      recovery, and additional DnaK was produced during the recovery process. Overall,
      higher intracellular concentrations of DnaK tended to enhance cell resistance to
      a subsequent lethal stress. Indeed, E. coli cells that had undergone a sublethal
      heat shock (105 min at 55 degrees C, F(70)(10) = 3 min) accompanied by a 12-h
      recovery (containing 76,786 +/- 25,230 molecules/cell) resisted better than
      exponentially growing cells (38,500 +/- 6,056 molecules/cell) when later heated
      to 60 degrees C for 50 min (F(70)(10) = 5 min). Results reported here suggest
      that using stress protein to determine cell adaptation and survival, rather than
      cell counts alone, may lead to more efficient heat treatment.

PMID- 12788721
TI  - Unusual organization for lactose and galactose gene clusters in Lactobacillus
      helveticus.
AB  - The nucleotide sequences of the Lactobacillus helveticus lactose utilization
      genes were determined, and these genes were located and oriented relative to one
      another. The lacLM genes (encoding the beta-galactosidase protein) were in a
      divergent orientation compared to lacR (regulatory gene) and lacS (lactose
      transporter). Downstream from lacM was an open reading frame (galE) encoding a
      UDP-galactose 4 epimerase, and the open reading frame had the same orientation as
      lacM. The lacR gene was separated from the downstream lacS gene by 2.0 kb of DNA
      containing several open reading frames that were derived from fragmentation of
      another permease gene (lacS'). Northern blot analysis revealed that lacL, lacM,
      and galE made up an operon that was transcribed in the presence of lactose from
      an upstream lacL promoter. The inducible genes lacL and lacM were regulated at
      the transcriptional level by the LacR repressor. In the presence of glucose and
      galactose galE was transcribed from its promoter, suggesting that the
      corresponding enzyme can be expressed constitutively. Lactose transport was
      inducible by addition of lactose to the growth medium.

PMID- 12788722
TI  - Involvement of the reserve material poly-beta-hydroxybutyrate in Azospirillum
      brasilense stress endurance and root colonization.
AB  - When grown under suboptimal conditions, rhizobacteria of the genus Azospirillum
      produce high levels of poly-beta-hydroxybutyrate (PHB). Azospirillum brasilense
      strain Sp7 and a phbC (PHB synthase) mutant strain in which PHB production is
      impaired were evaluated for metabolic versatility, for the ability to endure
      various stress conditions, for survival in soil inoculants, and for the potential
      to promote plant growth. The carbon source utilization data were similar for the
      wild-type and mutant strains, but the generation time of the wild-type strain was
      shorter than that of the mutant strain with all carbon sources tested. The
      ability of the wild type to endure UV irradiation, heat, osmotic pressure,
      osmotic shock, and desiccation and to grow in the presence of hydrogen peroxide
      was greater than that of the mutant strain. The motility and cell aggregation of
      the mutant strain were greater than the motility and cell aggregation of the wild
      type. However, the wild type exhibited greater chemotactic responses towards
      attractants than the mutant strain exhibited. The wild-type strain exhibited
      better survival than the mutant strain in carrier materials used for soil
      inoculants, but no difference in the ability to promote plant growth was detected
      between the strains. In soil, the two strains colonized roots to the same extent.
      It appears that synthesis and utilization of PHB as a carbon and energy source by
      A. brasilense under stress conditions favor establishment of this bacterium and
      its survival in competitive environments. However, in A. brasilense, PHB
      production does not seem to provide an advantage in root colonization under the
      conditions tested.

PMID- 12788723
TI  - Carbon starvation can induce energy deprivation and loss of fermentative capacity
      in Saccharomyces cerevisiae.
AB  - Seven different strains of Saccharomyces cerevisiae were tested for the ability
      to maintain their fermentative capacity during 24 h of carbon or nitrogen
      starvation. Starvation was imposed by transferring cells, exponentially growing
      in anaerobic batch cultures, to a defined growth medium lacking either a carbon
      or a nitrogen source. After 24 h of starvation, fermentative capacity was
      determined by addition of glucose and measurement of the resulting ethanol
      production rate. The results showed that 24 h of nitrogen starvation reduced the
      fermentative capacity by 70 to 95%, depending on the strain. Carbon starvation,
      on the other hand, provoked an almost complete loss of fermentative capacity in
      all of the strains tested. The absence of ethanol production following carbon
      starvation occurred even though the cells possessed a substantial glucose
      transport capacity. In fact, similar uptake capacities were recorded irrespective
      of whether the cells had been subjected to carbon or nitrogen starvation.
      Instead, the loss of fermentative capacity observed in carbon-starved cells was
      almost surely a result of energy deprivation. Carbon starvation drastically
      reduced the ATP content of the cells to values well below 0.1 micro mol/g, while
      nitrogen-starved cells still contained approximately 6 micro mol/g after 24 h of
      treatment. Addition of a small amount of glucose (0.1 g/liter at a cell density
      of 1.0 g/liter) at the initiation of starvation or use of stationary-phase
      instead of log-phase cells enabled the cells to preserve their fermentative
      capacity also during carbon starvation. The prerequisites for successful
      adaptation to starvation conditions are probably gradual nutrient depletion and
      access to energy during the adaptation period.

PMID- 12788724
TI  - External pH and nitrogen source affect secretion of pectate lyase by
      Colletotrichum gloeosporioides.
AB  - Accumulation of ammonia and associated tissue alkalinization predispose fruit to
      attack by Colletotrichum gloeosporioides: As the external pH increases from 4.0
      to 6.0, pectate lyase (PL) and other extracellular proteins are secreted and
      accumulate. At pH 4.0 neither pelB (encoding PL) transcription nor PL secretion
      were detected; however, they were detected as the pH increased. Nitrogen
      assimilation also was required for PL secretion at pH 6.0. Both inorganic and
      organic nitrogen sources enhanced PL secretion at pH 6.0, but neither was
      sufficient for PL secretion at pH 4.0. Sequence analysis of the 5' upstream
      region of the pelB promoter revealed nine putative consensus binding sites for
      the Aspergillus transcription factor PacC. Consistent with this result, the
      transcript levels of pac1 (the C. gloeosporioides pacC homologue) and pelB
      increased in parallel as a function of pH. Our results suggest that the ambient
      pH and the nitrogen source are independent regulatory factors for processes
      linked to PL secretion and virulence of C. gloeosporioides.

PMID- 12788725
TI  - Identification and characterization of the conjugal transfer region of the pCg1
      plasmid from naphthalene-degrading Pseudomonas putida Cg1.
AB  - Hybridization and restriction fragment length polymorphism data (K. G. Stuart
      Keil, A. M. Hohnstock, K. P. Drees, J. B. Herrick, and E. L. Madsen, Appl.
      Environ. Microbiol. 64:3633-3640, 1998) have shown that pCg1, a naphthalene
      catabolic plasmid carried by Pseudomonas putida Cg1, is homologous to the
      archetypal naphthalene catabolic plasmid, pDTG1, in P. putida NCIB 9816-4.
      Sequencing of the latter plasmid allowed PCR primers to be designed for
      amplifying and sequencing the conjugal transfer region in pCg1. The mating pair
      formation (mpf) gene, mpfA encoding the putative precursor of the conjugative
      pilin subunit from pCg1, was identified along with other trb-like mpf genes.
      Sequence comparison revealed that the 10 mpf genes in pCg1 and pDTG1 are closely
      related (61 to 84% identity) in sequence and operon structure to the putative mpf
      genes of catabolic plasmid pWW0 (TOL plasmid of P. putida) and pM3 (antibiotic
      resistance plasmid of Pseudomonas. spp). A polar mutation caused by insertional
      inactivation in mpfA of pCg1 and reverse transcriptase PCR analysis of mRNA
      showed that this mpf region was involved in conjugation and was transcribed from
      a promoter located upstream of an open reading frame adjacent to mpfA. lacZ
      transcriptional fusions revealed that mpf genes of pCg1 were expressed
      constitutively both in liquid and on solid media. This expression did not respond
      to host exposure to naphthalene. Conjugation frequency on semisolid media was
      consistently 10- to 100-fold higher than that in liquid media. Thus, conjugation
      of pCg1 in P. putida Cg1 was enhanced by expression of genes in the mpf region
      and by surfaces where conditions fostering stable, high-density cell-to-cell
      contact are manifest.

PMID- 12788726
TI  - The bacterium Thermus thermophilus, like hyperthermophilic archaea, uses a two
      step pathway for the synthesis of mannosylglycerate.
AB  - The biosynthetic pathway for the synthesis of the compatible solute alpha
      mannosylglycerate (MG) in the thermophilic bacterium Thermus thermophilus HB27
      was identified based on the activities of recombinant mannosyl-3-phosphoglycerate
      synthase (MPGS) (EC 2.4.1.217) and mannosyl-3-phosphoglycerate phosphatase (MPGP)
      (EC 3.1.3.70). The sequences of homologous genes from the archaeon Pyrococcus
      horikoshii were used to identify MPGS and MPGP genes in T. thermophilus HB27
      genome. Both genes were separately cloned and overexpressed in Escherichia coli,
      yielding 3 to 4 mg of pure recombinant protein per liter of culture. The
      molecular masses were 43.6 and 28.1 kDa for MPGS and MPGP, respectively. The
      recombinant MPGS catalyzed the synthesis of alpha-mannosyl-3-phosphoglycerate
      (MPG) from GDP-mannose and D-3-phosphoglycerate, while the recombinant MPGP
      catalyzed the dephosphorylation of MPG to MG. The recombinant MPGS had optimal
      activity at 80 to 90 degrees C and a pH optimum near 7.0; MPGP had maximal
      activity between 90 and 95 degrees C and at pH 6.0. The activities of both
      enzymes were strictly dependent on divalent cations; Mn(2+) was most effective
      for MPGS, while Mn(2+), Co(2+), Mg(2+), and to a lesser extent Ni(2+) activated
      MPGP. The organization of MG biosynthetic genes in T. thermophilus HB27 is
      different from the P. horikoshii operon-like structure, since the genes involved
      in the conversion of fructose-6-phosphate to GDP-mannose are not found
      immediately downstream of the contiguous MPGS and MPGP genes. The biosynthesis of
      MG in the thermophilic bacterium T. thermophilus HB27, proceeding through a
      phosphorylated intermediate, is similar to the system found in hyperthermophilic
      archaea.

PMID- 12788727
TI  - Distribution of biosurfactant-producing bacteria in undisturbed and contaminated
      arid Southwestern soils.
AB  - Biosurfactants are a unique class of compounds that have been shown to have a
      variety of potential applications in the remediation of organic- and metal
      contaminated sites, in the enhanced transport of bacteria, in enhanced oil
      recovery, as cosmetic additives, and in biological control. However, little is
      known about the distribution of biosurfactant-producing bacteria in the
      environment. The goal of this study was to determine how common culturable
      surfactant-producing bacteria are in undisturbed and contaminated sites. A series
      of 20 contaminated (i.e., with metals and/or hydrocarbons) and undisturbed soils
      were collected and plated on R(2)A agar. The 1,305 colonies obtained were
      screened for biosurfactant production in mineral salts medium containing 2%
      glucose. Forty-five of the isolates were positive for biosurfactant production,
      representing most of the soils tested. The 45 isolates were grouped by using
      repetitive extragenic palindromic (REP)-PCR analysis, which yielded 16 unique
      isolates. Phylogenetic relationships were determined by comparing the 16S rRNA
      gene sequence of each unique isolate with known sequences, revealing one new
      biosurfactant-producing microbe, a Flavobacterium sp. Sequencing results
      indicated only 10 unique isolates (in comparison to the REP analysis, which
      indicated 16 unique isolates). Surface tension results demonstrated that isolates
      that were similar according to sequence analysis but unique according to REP
      analysis in fact produced different surfactant mixtures under identical growth
      conditions. These results suggest that the 16S rRNA gene database commonly used
      for determining phylogenetic relationships may miss diversity in microbial
      products (e.g., biosurfactants and antibiotics) that are made by closely related
      isolates. In summary, biosurfactant-producing microorganisms were found in most
      soils even by using a relatively limited screening assay. Distribution was
      dependent on soil conditions, with gram-positive biosurfactant-producing isolates
      tending to be from heavy metal-contaminated or uncontaminated soils and gram
      negative isolates tending to be from hydrocarbon-contaminated or cocontaminated
      soils.

PMID- 12788728
TI  - Assessment of bioavailability of soil-sorbed atrazine.
AB  - Bioavailability of pesticides sorbed to soils is an important determinant of
      their environmental fate and impact. Mineralization of sorbed atrazine was
      studied in soil and clay slurries, and a desorption-biodegradation-mineralization
      (DBM) model was developed to quantitatively evaluate the bioavailability of
      sorbed atrazine. Three atrazine-degrading bacteria that utilized atrazine as a
      sole N source (Pseudomonas sp. strain ADP, Agrobacterium radiobacter strain J14a,
      and Ralstonia sp. strain M91-3) were used in the bioavailability assays. Assays
      involved establishing sorption equilibrium in sterile soil slurries, inoculating
      the system with organisms, and measuring the CO(2) production over time. Sorption
      and desorption isotherm analyses were performed to evaluate distribution
      coefficients and desorption parameters, which consisted of three desorption site
      fractions and desorption rate coefficients. Atrazine sorption isotherms were
      linear for mineral and organic soils but displayed some nonlinearity for K
      saturated montmorillonite. The desorption profiles were well described by the
      three-site desorption model. In many instances, the mineralization of atrazine
      was accurately predicted by the DBM model, which accounts for the extents and
      rates of sorption/desorption processes and assumes biodegradation of liquid
      phase, but not sorbed, atrazine. However, for the Houghton muck soil, which
      manifested the highest sorbed atrazine concentrations, enhanced mineralization
      rates, i.e., greater than those expected on the basis of aqueous-phase atrazine
      concentration, were observed. Even the assumption of instantaneous desorption
      could not account for the elevated rates. A plausible explanation for enhanced
      bioavailability is that bacteria access the localized regions where atrazine is
      sorbed and that the concentrations found support higher mineralization rates than
      predicted on the basis of aqueous-phase concentrations. Characteristics of high
      sorbed-phase concentration, chemotaxis, and attachment of cells to soil particles
      seem to contribute to the bioavailability of soil-sorbed atrazine.

PMID- 12788729
TI  - Consensus-degenerate hybrid oligonucleotide primers for amplification of priming
      glycosyltransferase genes of the exopolysaccharide locus in strains of the
      Lactobacillus casei group.
AB  - A primer design strategy named CODEHOP (consensus-degenerate hybrid
      oligonucleotide primer) for amplification of distantly related sequences was used
      to detect the priming glycosyltransferase (GT) gene in strains of the
      Lactobacillus casei group. Each hybrid primer consisted of a short 3' degenerate
      core based on four highly conserved amino acids and a longer 5' consensus clamp
      region based on six sequences of the priming GT gene products from
      exopolysaccharide (EPS)-producing bacteria. The hybrid primers were used to
      detect the priming GT gene of 44 commercial isolates and reference strains of
      Lactobacillus rhamnosus, L. casei, Lactobacillus zeae, and Streptococcus
      thermophilus. The priming GT gene was detected in the genome of both non-EPS
      producing (EPS(-)) and EPS-producing (EPS(+)) strains of L. rhamnosus. The
      sequences of the cloned PCR products were similar to those of the priming GT gene
      of various gram-negative and gram-positive EPS(+) bacteria. Specific primers
      designed from the L. rhamnosus RW-9595M GT gene were used to sequence the end of
      the priming GT gene in selected EPS(+) strains of L. rhamnosus. Phylogenetic
      analysis revealed that Lactobacillus spp. form a distinctive group apart from
      other lactic acid bacteria for which GT genes have been characterized to date.
      Moreover, the sequences show a divergence existing among strains of L. rhamnosus
      with respect to the terminal region of the priming GT gene. Thus, the PCR
      approach with consensus-degenerate hybrid primers designed with CODEHOP is a
      practical approach for the detection of similar genes containing conserved motifs
      in different bacterial genomes.

PMID- 12788730
TI  - Characterization of urease-positive thermophilic Campylobacter subspecies by
      multilocus enzyme electrophoresis typing.
AB  - Thirty-one urease-positive thermophilic Campylobacter (UPTC) isolates, including
      three reference strains (NCTC12892, NCTC12895 and NCTC12896), and three
      Campylobacter lari isolates, which were isolated from several countries and
      sources, were compared genotypically by using multilocus enzyme electrophoresis
      (MLEE). We examined allelic variation around seven enzyme loci, including the
      adenylate kinase, alkaline phosphatase, catalase, fumarase, malic enzyme, malate
      dehydrogenase, and L-phenylalanyl-L-leucine peptidase loci. MLEE typing revealed
      the presence of 23 different electrophoretic types (ETs) among the 31 UPTC
      isolates, and 14 isolates shared six electrophoretic profiles. Three different
      ETs were identified for the three C. lari isolates examined, and no ETs were
      shared by UPTC and C. lari isolates. Quantitative analyses were subsequently
      performed by using allelic variation data, and the results demonstrated that the
      mean genetic diversity was 0.655. In conclusion, MLEE demonstrated that the UPTC
      isolates examined are genetically hypervariable and form a cluster separate from
      the C. lari cluster.

PMID- 12788731
TI  - Isolation of a methanogen from deep marine sediments that contain methane
      hydrates, and description of Methanoculleus submarinus sp. nov.
AB  - We isolated a methanogen from deep in the sediments of the Nankai Trough off the
      eastern coast of Japan. At the sampling site, the water was 950 m deep and the
      sediment core was collected at 247 m below the sediment surface. The isolated
      methanogen was named Nankai-1. Cells of Nankai-1 were nonmotile and highly
      irregular coccoids (average diameter, 0.8 to 2 micro m) and grew with hydrogen or
      formate as a catabolic substrate. Cells required acetate as a carbon source.
      Yeast extract and peptones were not required but increased the growth rate. The
      cells were mesophilic, growing most rapidly at 45 degrees C (no growth at </=10
      degrees C or >/=55 degrees C). Cells grew with a maximum specific growth rate of
      2.43 day(-1) at 45 degrees C. Cells grew at pH values between 5.0 and 8.7 but did
      not grow at pH 4.7 or 9.0. Strain Nankai-1 grew in a wide range of salinities,
      from 0.1 to 1.5 M Na(+). The described phenotypic characteristics of this novel
      isolate were consistent with the in situ environment of the Nankai Trough. This
      is the first report of a methanogenic isolate from methane hydrate-bearing
      sediments. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it
      is most closely related to Methanoculleus marisnigri (99.1% sequence similarity),
      but DNA hybridization experiments indicated a DNA sequence similarity of only
      49%. Strain Nankai-1 was also found to be phenotypically similar to M.
      marisnigri, but two major phenotypic differences were found: strain Nankai-1 does
      not require peptones, and it grows fastest at a much higher temperature. We
      propose a new species, Methanoculleus submarinus, with strain Nankai-1 as the
      type strain.

PMID- 12788732
TI  - Fluorescent heteroduplex assay for monitoring Bacillus anthracis and close
      relatives in environmental samples.
AB  - A fluorescent heteroduplex method was developed to assess the presence of 16S
      rRNA gene (rDNA) sequences from Bacillus anthracis and close relatives in PCR
      amplified 16S rDNA sequence mixtures from environmental samples. The method uses
      a single-stranded, fluorescent DNA probe, 464 nucleotides in length, derived from
      a B. anthracis 16S rRNA gene. The probe contains a unique, engineered deletion
      such that all probe-target duplexes are heteroduplexes with an unpaired G at
      position 343 (deltaG343). Heteroduplex profiles of sequences >/=85% similar to
      the probe were produced using an ABI 377 sequencer in less than 3 h. The method
      divides strains of the Bacillus cereus-Bacillus thuringiensis-B. anthracis group
      into two subgroups. Each subgroup is defined by a specific 16S rRNA gene sequence
      type. Sequence type A, containing one mismatch with the probe, occurs in B.
      anthracis and a small number of closely related clonal lineages represented
      mostly by food-borne pathogenic isolates of B. cereus and B. thuringiensis.
      Sequence type B, containing two mismatches with the probe, is found in the
      majority of B. cereus and B. thuringiensis strains examined to date. Sequence
      types A and B, when hybridized to the probe, generate two easily differentiated
      heteroduplexes. Thus, from heteroduplex profiles, the presence of B. cereus-B.
      thuringiensis-B. anthracis subgroups in environmental samples can be inferred
      unambiguously. The results show that fluorescent heteroduplex analysis is an
      effective profiling technique for detection and differentiation of sequences
      representing small phylogenetic or functional groups in environmental samples.

PMID- 12788733
TI  - Microbiological evaluation of a range of disinfectant products to control mixed
      species biofilm contamination in a laboratory model of a dental unit water
      system.
AB  - Dental unit water system (DUWS) tubing harbors complex multispecies biofilms that
      are responsible for high microbial levels at the distal outlet. The aim of this
      study was to use an established biofilm laboratory model to simulate biofouling
      of DUWS to evaluate practical, cost-effective, and evidence-based methods of
      microbial decontamination. Reproducible biofilms were developed in the model over
      14 days; decontamination was assessed using total viable counts (TVC) and
      microscopic-image analysis techniques to view the inner surface of tubing.
      Flushing did not reduce the biofilm coverage or TVC. Combizyme and ozone did not
      completely eliminate the viable bacteria (70 and 65% reduction in biofilm TVC,
      respectively), nor did they remove the biofilm (45 and 57% reduction in biofilm
      coverage, respectively). Chlorhexidine and Bio2000 (active agent: ethanol and
      chlorhexidine), Tegodor and Gigasept Rapid (aldehyde based), and Grotanol
      (hydroxide based) completely eliminated the TVC but did not completely remove
      biofilm (31, 53 33, 34, and 64.9% reduction of biofilm coverage, respectively).
      Other products including Grotanol Flussig (phenol based), Betadine (povidone
      iodine based), Alpron (chlorite based), and the hydroxide-containing products
      Sporklenz, Sterilex Ultra, Dialox, Sterilox, Sanosil, Oxigenal, and Grotanat
      Bohrerbad resulted in a 100% reduction in the biofilm TVC and a >95% reduction in
      biofilm coverage. The study demonstrated that while many disinfectants achieve a
      sufficient reduction in TVC they may not necessarily remove unwanted biofilm from
      the tubing surfaces as tested in this laboratory-controlled biofilm model.

PMID- 12788734
TI  - Identification and manipulation of soil properties to improve the biological
      control performance of phenazine-producing Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens 2-79RN(10) protects wheat against take-all disease caused
      by Gaeumannomyces graminis var. tritici; however, the level of protection in the
      field varies from site to site. Identification of soil factors that exert the
      greatest influence on disease suppression is essential to improving biocontrol.
      In order to assess the relative importance of 28 soil properties on take-all
      suppression, seeds were treated with strain 2-79RN(10) (which produces phenazine
      1-carboxylate [PCA(+)]) or a series of mutants with PCA(+) and PCA(-) phenotypes.
      Bacterized seeds were planted in 10 soils, representative of the wheat-growing
      region in the Pacific Northwest. Sixteen soil properties were correlated with
      disease suppression. Biocontrol activity of PCA(+) strains was positively
      correlated with ammonium-nitrogen, percent sand, soil pH, sodium (extractable and
      soluble), sulfate-sulfur, and zinc. In contrast, biocontrol was negatively
      correlated with cation-exchange capacity (CEC), exchangeable acidity, iron,
      manganese, percent clay, percent organic matter (OM), percent silt, total carbon,
      and total nitrogen. Principal component factor analysis of the 16 soil properties
      identified a three-component solution that accounted for 87 percent of the
      variance in disease rating (biocontrol). A model was identified with step-wise
      regression analysis (R(2) = 0.96; Cp statistic = 6.17) that included six key soil
      properties: ammonium-nitrogen, CEC, iron, percent silt, soil pH, and zinc. As
      predicted by our regression model, the biocontrol activity of 2-79RN(10) was
      improved by amending a soil low in Zn with 50 micro g of zinc-EDTA/g of soil. We
      then investigated the negative correlation of OM with disease suppression and
      found that addition of OM (as wheat straw) at rates typical of high-OM soils
      significantly reduced biocontrol activity of 2-79RN(10).

PMID- 12788735
TI  - Interactions of insecticidal toxin gene products from Xenorhabdus nematophilus
      PMFI296.
AB  - Four genes on a genomic fragment from Xenorhabdus nematophilus PMFI296 were shown
      to be involved in insecticidal activity towards three commercially important
      insect species. Each gene was expressed individually and in combinations in
      Escherichia coli, and the insecticidal activity of the lysates was determined.
      The combined four genes (xptA1, xptA2, xptB1, and xptC1), in E. coli, showed
      activity towards Pieris brassicae, Pieris rapae, and Heliothis virescens. The
      genes xptA1, xptB1, and xptC1 were involved in expressing activity towards P.
      rapae and P. brassicae, while the genes xptA2, xptB1, and xptC1 were needed for
      activity towards H. virescens. When each of these three genes was expressed
      individually in E. coli and the cell lysates were used in insect assays or mixed
      and then used, insecticidal activity was detected at a very low level. If the
      genes xptB1 and xptC1 were expressed in the same E. coli cell and this cell
      lysate was mixed with cells expressing xptA1, activity was restored to P. rapae
      and P. brassicae. Similarly mixing XptB1/C1 lysate with XptA2 lysate restored
      activity towards H. virescens. Individual gene disruptions in X. nematophilus
      PMFI296 reduced activity to insects; this activity was restored by
      complementation with cells expressing either xptA1 or xptA2 for their respective
      disruptions or E. coli expressing both xptB1 and xptC1 for individual disruptions
      of either of these genes. The genes xptA2, xptC1, and xptB1 were expressed as an
      operon in PMFI296 and inactivation of xptA2 or xptC1 resulted in silencing of
      downstream gene(s), while xptA1 was expressed as a single gene. Therefore, the
      two three gene product combinations interact with each other to produce good
      insecticidal activity.

PMID- 12788736
TI  - Detection and enumeration of aromatic oxygenase genes by multiplex and real-time
      PCR.
AB  - Our abilities to detect and enumerate pollutant-biodegrading microorganisms in
      the environment are rapidly advancing with the development of molecular genetic
      techniques. Techniques based on multiplex and real-time PCR amplification of
      aromatic oxygenase genes were developed to detect and quantify aromatic catabolic
      pathways, respectively. PCR primer sets were identified for the large subunits of
      aromatic oxygenases from alignments of known gene sequences and tested with
      genetically well-characterized strains. In all, primer sets which allowed
      amplification of naphthalene dioxygenase, biphenyl dioxygenase, toluene
      dioxygenase, xylene monooxygenase, phenol monooxygenase, and ring-hydroxylating
      toluene monooxygenase genes were identified. For each primer set, the length of
      the observed amplification product matched the length predicted from published
      sequences, and specificity was confirmed by hybridization. Primer sets were
      grouped according to the annealing temperature for multiplex PCR permitting
      simultaneous detection of various genotypes responsible for aromatic hydrocarbon
      biodegradation. Real-time PCR using SYBR green I was employed with the individual
      primer sets to determine the gene copy number. Optimum polymerization
      temperatures for real-time PCR were determined on the basis of the observed
      melting temperatures of the desired products. When a polymerization temperature
      of 4 to 5 degrees C below the melting temperature was used, background
      fluorescence signals were greatly reduced, allowing detection limits of 2 x 10(2)
      copies per reaction mixture. Improved in situ microbial characterization will
      provide more accurate assessment of pollutant biodegradation, enhance studies of
      the ecology of contaminated sites, and facilitate assessment of the impact of
      remediation technologies on indigenous microbial populations.

PMID- 12788737
TI  - A stable bioluminescent construct of Escherichia coli O157:H7 for hazard
      assessments of long-term survival in the environment.
AB  - A chromosomally lux-marked (Tn5 luxCDABE) strain of nontoxigenic Escherichia coli
      O157:H7 was constructed by transposon mutagenesis and shown to have retained the
      O157, H7, and intimin phenotypes. The survival characteristics of this strain in
      the experiments performed (soil at -5, -100, and -1,500 kPa matric potential and
      artificial groundwater) were indistinguishable from the wild-type strain.
      Evaluation of potential luminescence was found to be a rapid, cheap, and
      quantitative measure of viable E. coli O157:H7 Tn5 luxCDABE populations in
      environmental samples. In the survival studies, bioluminescence of the starved
      populations of E. coli O157:H7 Tn5 luxCDABE could be reactivated to the original
      levels of light emission, suggesting that these populations remain viable and
      potentially infective to humans. The attributes of the construct offer a cheap
      and low-risk substitute to the use of verocytotoxin-producing E. coli O157:H7 in
      long-term survival studies.

PMID- 12788738
TI  - Development of a Listeria monocytogenes EGDe partial proteome reference map and
      comparison with the protein profiles of food isolates.
AB  - A partially annotated proteome reference map of the food pathogen Listeria
      monocytogenes was developed for exponentially growing cells under standardized,
      optimal conditions by using the sequenced strain EGDe (serotype 1/2a) as a model
      organism. The map was developed by using a reproducible total protein extraction
      and two-dimensional (2-D) polyacrylamide gel electrophoresis analysis procedure,
      and it contained 33 identified proteins representing the four main protein
      functional classes. In order to facilitate analysis of membrane proteins, a
      protein compartmentalization procedure was assessed. The method used provided
      partial fractionation of membrane and cytosolic proteins. The total protein 2-D
      profiles of three serotype 1/2a strains and one serotype 1/2b strain isolated
      from food were compared to the L. monocytogenes EGDe proteome. An average of 13%
      of the major protein spots in the food strain proteomes were not matched in the
      strain EGDe proteome. The variation was greater for the less intense spots, and
      on average 28% of these spots were not matched. Two of the proteins identified in
      L. monocytogenes EGDe were missing in one or more of the food isolates. These two
      proteins were proteins involved in the main glycolytic pathway and in metabolism
      of coenzymes and prosthetic groups. The two corresponding genes were found by PCR
      amplification to be present in the four food isolates. Our results show that the
      L. monocytogenes EGDe reference map is a valuable starting point for analyses of
      strains having various origins and could be useful for analyzing the proteomes of
      different isolates of this pathogen.

PMID- 12788739
TI  - Determination of the domain of the Lactobacillus delbrueckii subsp. bulgaricus
      cell surface proteinase PrtB involved in attachment to the cell wall after
      heterologous expression of the prtB gene in Lactococcus lactis.
AB  - Belonging to the subtilase family, the cell surface proteinase (CSP) PrtB of
      Lactobacillus delbrueckii subsp. bulgaricus differs from other CSPs synthesized
      by lactic acid bacteria. Expression of the prtB gene under its own promoter was
      shown to complement the proteinase-deficient strain MG1363 (PrtP(-) PrtM(-)) of
      Lactococcus lactis subsp. cremoris. Surprisingly, the maturation process of PrtB,
      unlike that of lactococcal CSP PrtPs, does not require a specific PrtM-like
      chaperone. The carboxy end of PrtB was previously shown to be different from the
      consensus anchoring region of other CSPs and exhibits an imperfect duplication of
      59 amino acids with a high lysine content. By using a deletion strategy, the
      removal of the last 99 amino acids, including the degenerated anchoring signal
      (LPKKT), was found to be sufficient to release a part of the truncated PrtB into
      the culture medium and led to an increase in PrtB activity. This truncated PrtB
      is still active and enables L. lactis MG1363 to grow in milk supplemented with
      glucose. By contrast, deletion of the last 806 amino acids of PrtB led to the
      secretion of an inactive proteinase. Thus, the utmost carboxy end of PrtB is
      involved in attachment to the bacterial cell wall. Proteinase PrtB constitutes a
      powerful tool for cell surface display of heterologous proteins like antigens.

PMID- 12788740
TI  - Development of a thermally regulated broad-spectrum promoter system for use in
      pathogenic gram-positive species.
AB  - Selectively regulating gene expression is an essential molecular tool that is
      lacking for many pathogenic gram-positive bacteria. In this report, we describe
      the evaluation of a series of promoters regulated by the bacteriophage P1
      temperature-sensitive C1 repressor in Enterococcus faecium, Enterococcus
      faecalis, and Staphylococcus aureus. Using the lacZ gene to monitor gene
      expression, we examined the strength, basal expression, and induced expression of
      synthetic promoters carrying C1 operator sites. The promoters exhibited extremely
      low basal expression and, under inducing conditions, gave high levels of
      expression (100- to 1,000-fold induction). We demonstrate that the promoter
      system could be modulated by temperature and showed rapid induction and that the
      mechanism of regulation occurred at the level of transcription. Controlled
      expression with the same constructs was also demonstrated in the gram-negative
      bacterium Escherichia coli. However, low basal expression and the ability to
      achieve derepression were dependent on both the number of mismatches in the C1
      operator sites and the promoter driving c1 expression. Since the promoters were
      designed to contain conserved promoter elements from gram-positive species and
      were constructed in a broad-host-range plasmid, this system will provide a new
      opportunity for controlled gene expression in a variety of gram-positive
      bacteria.

PMID- 12788741
TI  - Giardia cysts in wastewater treatment plants in Italy.
AB  - Reductions in annual rainfall in some regions and increased human consumption
      have caused a shortage of water resources at the global level. The recycling of
      treated wastewaters has been suggested for certain domestic, industrial, and
      agricultural activities. The importance of microbiological and parasitological
      criteria for recycled water has been repeatedly emphasized. Among water-borne
      pathogens, protozoa of the genera Giardia and Cryptosporidium are known to be
      highly resistant to water treatment procedures and to cause outbreaks through
      contaminated raw or treated water. We conducted an investigation in four
      wastewater treatment plants in Italy by sampling wastewater at each stage of the
      treatment process over the course of 1 year. The presence of the parasites was
      assessed by immunofluorescence with monoclonal antibodies. While Cryptosporidium
      oocysts were rarely observed, Giardia cysts were detected in all samples
      throughout the year, with peaks observed in autumn and winter. The overall
      removal efficiency of cysts in the treatment plants ranged from 87.0 to 98.4%.
      The removal efficiency in the number of cysts was significantly higher when the
      secondary treatment consisted of active oxidation with O(2) and sedimentation
      instead of activated sludge and sedimentation (94.5% versus 72.1 to 88.0%; P =
      0.05, analysis of variance). To characterize the cysts at the molecular level,
      the beta-giardin gene was PCR amplified, and the products were sequenced or
      analyzed by restriction. Cysts were typed as assemblage A or B, both of which are
      human pathogens, stressing the potential risk associated with the reuse of
      wastewater.

PMID- 12788742
TI  - Use of antibiotic resistance analysis for representativeness testing of
      multiwatershed libraries.
AB  - The use of antibiotic resistance analysis (ARA) for microbial source tracking
      requires the generation of a library of isolates collected from known sources in
      the watershed. The size and composition of the library are critical in
      determining if it represents the diversity of patterns found in the watershed.
      This study was performed to determine the size that an ARA library needs to be to
      be representative of the watersheds for which it will be used and to determine if
      libraries from different watersheds can be merged to create multiwatershed
      libraries. Fecal samples from known human, domesticated, and wild animal sources
      were collected from six Virginia watersheds. From these samples, enterococci were
      isolated and tested by ARA. Based on cross-validation discriminant analysis, only
      the largest of the libraries (2,931 isolates) were found to be able to classify
      nonlibrary isolates as well as library isolates (i.e., were representative).
      Small libraries tended to have higher average rates of correct classification,
      but were much less able to correctly classify nonlibrary isolates. A merged
      multiwatershed library (6,587 isolates) was created and was found to be large
      enough to be representative of the isolates from the contributing watersheds.
      When isolates that were collected from the contributing watersheds approximately
      1 year later were analyzed with the multiwatershed library, they were classified
      as well as the isolates in the library, suggesting that the resistance patterns
      are temporally stable for at least 1 year. The ability to obtain a
      representative, temporally stable library demonstrates that ARA can be used to
      identify sources of fecal pollution in natural waters.

PMID- 12788743
TI  - Increasing the oxidative stress response allows Escherichia coli to overcome
      inhibitory effects of condensed tannins.
AB  - Tannins are plant-derived polyphenols with antimicrobial effects. The mechanism
      of tannin toxicity towards Escherichia coli was determined by using an extract
      from Acacia mearnsii (Black wattle) as a source of condensed tannins
      (proanthocyanidins). E. coli growth was inhibited by tannins only when tannins
      were exposed to oxygen. Tannins auto-oxidize, and substantial hydrogen peroxide
      was generated when they were added to aerobic media. The addition of exogenous
      catalase permitted growth in tannin medium. E. coli mutants that lacked HPI, the
      major catalase, were especially sensitive to tannins, while oxyR mutants that
      constitutively overexpress antioxidant enzymes were resistant. A tannin-resistant
      mutant was isolated in which a promoter-region point mutation increased the level
      of HPI by 10-fold. Our results indicate that wattle condensed tannins are toxic
      to E. coli in aerobic medium primarily because they generate H(2)O(2). The
      oxidative stress response helps E. coli strains to overcome their inhibitory
      effect.

PMID- 12788744
TI  - Microbial diversity of biofilms in dental unit water systems.
AB  - We investigated the microbial diversity of biofilms found in dental unit water
      systems (DUWS) by three methods. The first was microscopic examination by
      scanning electron microscopy (SEM), acridine orange staining, and fluorescent in
      situ hybridization (FISH). Most bacteria present in the biofilm were viable. FISH
      detected the beta and gamma, but not the alpha, subclasses of Proteobacteria: In
      the second method, 55 cultivated biofilm isolates were identified with the Biolog
      system, fatty acid analysis, and 16S ribosomal DNA (rDNA) sequencing. Only 16S
      identified all 55 isolates, which represented 13 genera. The most common
      organisms, as shown by analyses of 16S rDNA, belonged to the genera Afipia (28%)
      and Sphingomonas (16%). The third method was a culture-independent direct
      amplification and sequencing of 165 subclones from community biofilm 16S rDNA.
      This method revealed 40 genera: the most common ones included Leptospira (20%),
      Sphingomonas (14%), Bacillus (7%), Escherichia (6%), Geobacter (5%), and
      Pseudomonas (5%). Some of these organisms may be opportunistic pathogens. Our
      results have demonstrated that a biofilm in a health care setting may harbor a
      vast diversity of organisms. The results also reflect the limitations of culture
      based techniques to detect and identify bacteria. Although this is the greatest
      diversity reported in DUWS biofilms, other genera may have been missed. Using a
      technique based on jackknife subsampling, we projected that a 25-fold increase in
      the number of subclones sequenced would approximately double the number of genera
      observed, reflecting the richness and high diversity of microbial communities in
      these biofilms.

PMID- 12788745
TI  - Metabolic engineering of Escherichia coli for production of enantiomerically pure
      (R)-(--)-hydroxycarboxylic acids.
AB  - A heterologous metabolism of polyhydroxyalkanoate (PHA) biosynthesis and
      degradation was established in Escherichia coli by introducing the Ralstonia
      eutropha PHA biosynthesis operon along with the R. eutropha intracellular PHA
      depolymerase gene. By with this metabolically engineered E. coli,
      enantiomerically pure (R)-3-hydroxybutyric acid (R3HB) could be efficiently
      produced from glucose. By employing a two-plasmid system, developed as the PHA
      biosynthesis operon on a medium-copy-number plasmid and the PHA depolymerase gene
      on a high-copy-number plasmid, R3HB could be produced with a yield of 49.5%
      (85.6% of the maximum theoretical yield) from glucose. By integration of the PHA
      biosynthesis genes into the chromosome of E. coli and by introducing a plasmid
      containing the PHA depolymerase gene, R3HB could be produced without plasmid
      instability in the absence of antibiotics. This strategy can be used for the
      production of various enantiomerically pure (R)-hydroxycarboxylic acids from
      renewable resources.

PMID- 12788746
TI  - 1,8-dihydroxynaphthalene (DHN)-melanin biosynthesis inhibitors increase
      erythritol production in Torula corallina, and DHN-melanin inhibits erythrose
      reductase.
AB  - The yeast Torula corallina is a strong erythritol producer that is used in the
      industrial production of erythritol. However, melanin accumulation during culture
      represents a serious problem for the purification of erythritol from the
      fermentation broth. Melanin biosynthesis inhibitors such as 3,4
      dihydroxyphenylalanine and 1,8-dihydroxynaphthalene (DHN)-melanin inhibitors were
      added to the T. corallina cultures. Only the DHN-melanin inhibitors showed an
      effect on melanin production, which suggests that the melanin formed during the
      culturing of T. corallina is derived from DHN. This finding was confirmed by the
      detection of a shunt product of the pentaketide pathway, flaviolin, and elemental
      analysis. Among the DHN-melanin inhibitors, tricyclazole was the most effective.
      Supplementation with tricyclazole enhanced the production of erythritol while
      significantly inhibiting the production of DHN-melanin and DHN-melanin
      biosynthetic enzymes, such as trihydroxynaphthalene reductase. The erythrose
      reductase from T. corallina was purified to homogeneity by ion-exchange and
      affinity chromatography. Purified erythrose reductase was significantly inhibited
      in vitro in a noncompetitive manner by elevated levels of DHN-melanin. In
      contrast, the level of erythrose reductase activity was unaffected by increasing
      concentrations of tricyclazole. These results suggest that supplemental
      tricyclazole reduces the production of DHN-melanin, which may lead to a reduction
      in the inhibition of erythrose reductase and a higher yield of erythritol. This
      is the first report to demonstrate that melanin biosynthesis inhibitors increase
      the production of a sugar alcohol in T. corallina.

PMID- 12788747
TI  - Use of PCR for direct detection of Campylobacter species in bovine feces.
AB  - This study reports on the use of PCR to directly detect and distinguish
      Campylobacter species in bovine feces without enrichment. Inhibitors present in
      feces are a major obstacle to using PCR to detect microorganisms. The QIAamp DNA
      stool minikit was found to be an efficacious extraction method, as determined by
      the positive amplification of internal control DNA added to bovine feces before
      extraction. With nested or seminested multiplex PCR, Campylobacter coli, C.
      fetus, C. hyointestinalis, and C. jejuni were detected in all fecal samples
      inoculated at approximately 10(4) CFU g(-1), and 50 to 83% of the samples
      inoculated at approximately 10(3) CFU g(-1) were positive. At approximately 10(2)
      CFU g(-1), C. fetus, C. hyointestinalis, and C. jejuni (17 to 50% of the samples)
      but not C. coli were detected by PCR. From uninoculated bovine feces, a total of
      198 arbitrarily selected isolates of Campylobacter were recovered on four
      commonly used isolation media incubated at three temperatures. The most
      frequently isolated taxa were C. jejuni (152 isolates) and C. lanienae (42
      isolates), but isolates of C. fetus subsp. fetus, Arcobacter butzleri, and A.
      skirrowii also were recovered (</=2 isolates per taxon). Considerable variability
      was observed in the frequency of isolation of campylobacters among the four media
      and three incubation temperatures tested. With genus-specific primers,
      Campylobacter DNA was detected in 75% of the fecal samples, representing an 8%
      increase in sensitivity relative to that obtained with microbiological isolation
      across the four media and three incubation temperatures tested. With nested
      primers, C. jejuni and C. lanienae were detected in 25 and 67% of the samples,
      respectively. In no instance was DNA from either C. coli, C. fetus, or C.
      hyointestinalis detected in uninoculated bovine feces. PCR was more sensitive
      than isolation on microbiological media for detecting C. lanienae (17%) but not
      C. jejuni. Campylobacters are a diverse and fastidious group of bacteria, and the
      development of direct PCR not only will increase the understanding of
      Campylobacter species diversity and their frequency of occurrence in feces but
      also will enhance the knowledge of their role in the gastrointestinal tract of
      livestock and of the factors that influence shedding.

PMID- 12788749
TI  - Oxygen-insensitive nitroreductases NfsA and NfsB of Escherichia coli function
      under anaerobic conditions as lawsone-dependent Azo reductases.
AB  - Quinones can function as redox mediators in the unspecific anaerobic reduction of
      azo compounds by various bacterial species. These quinones are enzymatically
      reduced by the bacteria and the resulting hydroquinones then reduce in a purely
      chemical redox reaction the azo compounds outside of the cells. Recently, it has
      been demonstrated that the addition of lawsone (2-hydroxy-1,4-naphthoquinone) to
      anaerobically incubated cells of Escherichia coli resulted in a pronounced
      increase in the reduction rates of different sulfonated and polymeric azo
      compounds. In the present study it was attempted to identify the enzyme system(s)
      responsible for the reduction of lawsone by E. coli and thus for the lawsone
      dependent anaerobic azo reductase activity. An NADH-dependent lawsone reductase
      activity was found in the cytosolic fraction of the cells. The enzyme was
      purified by column chromatography and the amino-terminal amino acid sequence of
      the protein was determined. The sequence obtained was identical to the sequence
      of an oxygen-insensitive nitroreductase (NfsB) described earlier from this
      organism. Subsequent biochemical tests with the purified lawsone reductase
      activity confirmed that the lawsone reductase activity detected was identical
      with NfsB. In addition it was proven that also a second oxygen-insensitive
      nitroreductase of E. coli (NfsA) is able to reduce lawsone and thus to function
      under adequate conditions as quinone-dependent azo reductase.

PMID- 12788750
TI  - Evaluation of DNA extraction methods for use in combination with SYBR green I
      real-time PCR to detect Salmonella enterica serotype enteritidis in poultry.
AB  - The objective of this study was to develop a rapid, reproducible, and robust
      method for detecting Salmonella enterica serotype Enteritidis in poultry samples.
      First, for the extraction and purification of DNA from the preenrichment culture,
      four methods (boiling, alkaline lysis, Nucleospin, and Dynabeads DNA Direct
      System I) were compared. The most effective method was then combined with a real
      time PCR method based on the double-stranded DNA binding dye SYBR Green I used
      with the ABI Prism 7700 system. The specificity of the reaction was determined by
      the melting temperature (T(m)) of the amplicon obtained. The experiments were
      conducted both on samples of chicken experimentally contaminated with serotype
      Enteritidis and on commercially available poultry samples, which were also used
      for comparisons with the standard cultural method (i.e., ISO 6579/2001). The
      results of comparisons among the four DNA extraction methods showed significant
      differences except for the results from the boiling and Nucleospin methods (the
      two methods that produced the lowest threshold cycles). Boiling was selected as
      the preferred extraction method because it is the simplest and most rapid. This
      method was then combined with SYBR Green I real-time PCR, using primers SEFA-1
      and SEFA-2. The specificity of the reaction was confirmed by the T(m), which was
      consistently specific for the amplicon obtained; the mean peak T(m) obtained with
      curves specific for serotype Enteritidis was 82.56 +/- 0.22 degrees C. The
      standard curve constructed using the mean threshold cycle and various
      concentrations of serotype Enteritidis (ranging from 10(3) to 10(8) CFU/ml)
      showed good linearity (R(2) = 0.9767) and a sensitivity limit of less than 10(3)
      CFU/ml. The results of this study demonstrate that the SYBR Green I real-time PCR
      constitutes an effective and easy-to-perform method for detecting serotype
      Enteritidis in poultry samples.

PMID- 12788751
TI  - Glucose metabolism in Lactococcus lactis MG1363 under different aeration
      conditions: requirement of acetate to sustain growth under microaerobic
      conditions.
AB  - Lactococcus lactis subsp. lactis MG1363 was grown in batch cultures on a defined
      medium with glucose as the energy source under different aeration conditions,
      namely, anaerobic conditions, aerobic conditions, and microaerobic conditions
      with a dissolved oxygen tension of 5% (when saturation with air was used as the
      reference). The maximum specific growth rate was high (0.78 to 0.91 h(-1)) under
      all aeration conditions but decreased with increasing aeration, and more than 90%
      of the glucose was converted to lactate. However, a shift in by-product formation
      was observed. Increasing aeration resulted in acetate, CO(2), and acetoin
      replacing formate and ethanol as end products. Under microaerobic conditions,
      growth came to a gradual halt, although more than 60% of the glucose was still
      left. A decline in growth was not observed during microaerobic cultivation when
      acetate was added to the medium. We hypothesize that the decline in growth was
      due to a lack of acetyl coenzyme A (acetyl-CoA) needed for fatty acid synthesis
      since acetyl-CoA can be synthesized from acetate by means of acetate kinase and
      phosphotransacetylase activities.

PMID- 12788752
TI  - Secondary metabolites of Flustra foliacea and their influence on bacteria.
AB  - The North Sea bryozoan Flustra foliacea was investigated to determine its
      secondary metabolite content. Gas chromatography-mass spectrometry analysis of a
      dichloromethane extract of the bryozoan enabled 11 compounds to be identified.
      Preparative high-performance liquid chromatography of the extract resulted in the
      isolation of 10 brominated alkaloids (compounds 1 to 10) and one diterpene
      (compound 11). All of these compounds were tested to determine their activities
      in agar diffusion assays against bacteria derived from marine and terrestrial
      environments. Compounds 1, 3 to 7, 10, and 11 exhibited significant activities
      against one or more marine bacterial strains originally isolated from F. foliacea
      but only weak activities against all of the terrestrial bacteria. By using the
      biosensors Pseudomonas putida(pKR-C12), P. putida(pAS-C8), and Escherichia
      coli(pSB403) the antagonistic effect on N-acyl-homoserine lactone-dependent
      quorum-sensing systems was investigated. Compounds 8 and 10 caused reductions in
      the signal intensities in these bioassays ranging from 50 to 20% at a
      concentration of 20 micro g/ml.

PMID- 12788753
TI  - Nitric oxide reductase (norB) genes from pure cultures and environmental samples.
AB  - A PCR-based approach was developed to recover nitric oxide (NO) reductase (norB)
      genes as a functional marker gene for denitrifying bacteria. norB database
      sequences grouped in two very distinct branches. One encodes the quinol-oxidizing
      single-subunit class (qNorB), while the other class is a cytochrome bc-type
      complex (cNorB). The latter oxidizes cytochrome c, and the gene is localized
      adjacent to norC. While both norB types occur in denitrifying strains, the qnorB
      type was also found in a variety of nondenitrifying strains, suggesting a
      function in detoxifying NO. Branch-specific degenerate primer sets detected the
      two norB types in our denitrifier cultures. Specificity was confirmed by sequence
      analysis of the norB amplicons and failure to amplify norB from nondenitrifying
      strains. These primer sets also specifically amplified norB from freshwater and
      marine sediments. Pairwise comparison of amplified norB sequences indicated
      minimum levels of amino acid identity of 43.9% for qnorB and 38% for cnorB.
      Phylogenetic analysis confirmed the existence of two classes of norB genes, which
      clustered according to the respective primer set. Within the qnorB cluster, the
      majority of genes from isolates and a few environmental clones formed a separate
      subcluster. Most environmental qnorB clones originating from both habitats
      clustered into two distinct subclusters of novel sequences from presumably as yet
      uncultivated organisms. cnorB clones were located on separate branches within
      subclusters of genes from known organisms, suggesting an origin from similar
      organisms.

PMID- 12788754
TI  - Nutritional similarity between leaf-associated nonpathogenic bacteria and the
      pathogen is not predictive of efficacy in biological control of bacterial spot of
      tomato.
AB  - It has been demonstrated that for a nonpathogenic, leaf-associated bacterium,
      effectiveness in the control of bacterial speck of tomato is correlated with the
      similarity in the nutritional needs of the nonpathogenic bacterium and the
      pathogen Pseudomonas syringae pv. tomato. This relationship was investigated
      further in this study by using the pathogen Xanthomonas campestris pv.
      vesicatoria, the causal agent of bacterial spot of tomato, and a collection of
      nonpathogenic bacteria isolated from tomato foliage. The effects of inoculation
      of tomato plants with one of 34 nonpathogenic bacteria prior to inoculation with
      the pathogen X. campestris pv. vesicatoria were quantified by determining (i) the
      reduction in disease severity (number of lesions per square centimeter) in
      greenhouse assays and (ii) the reduction in leaf surface pathogen population size
      (log(10) of the number of CFU per leaflet) in growth chamber assays. Nutritional
      similarity between the nonpathogenic bacteria and X. campestris pv. vesicatoria
      was quantified by using either niche overlap indices (NOI) or relatedness in
      cluster analyses based upon in vitro utilization of carbon or nitrogen sources
      reported to be present in tomato tissues or in Biolog GN plates. In contrast to
      studies with P. syringae pv. tomato, nutritional similarity between the
      nonpathogenic bacteria and the pathogen X. campestris pv. vesicatoria was not
      correlated with reductions in disease severity. Nutritional similarity was also
      not correlated with reductions in pathogen population size. Further, the
      percentage of reduction in leaf surface pathogen population size was not
      correlated with the percentage of reduction in disease severity, suggesting that
      the epiphytic population size of X. campestris pv. vesicatoria is not related to
      disease severity and that X. campestris pv. vesicatoria exhibits behavior in the
      phyllosphere prior to lesion formation that is different from that of P. syringae
      pv. tomato.

PMID- 12788755
TI  - Rapid detection of Campylobacter coli, C. jejuni, and Salmonella enterica on
      poultry carcasses by using PCR-enzyme-linked immunosorbent assay.
AB  - Contamination of retail poultry by Campylobacter spp. and Salmonella enterica is
      a significant source of human diarrheal disease. Isolation and identification of
      these microorganisms require a series of biochemical and serological tests. In
      this study, Campylobacter ceuE and Salmonella invA genes were used to design
      probes in PCR-enzyme-linked immunosorbent assay (ELISA), as an alternative to
      conventional bacteriological methodology, for the rapid detection of
      Campylobacter jejuni, Campylobacter coli, and S. enterica from poultry samples.
      With PCR-ELISA (40 cycles), the detection limits for Salmonella and Campylobacter
      were 2 x 10(2) and 4 x 10(1) CFU/ml, respectively. ELISA increased the
      sensitivity of the conventional PCR method by 100- to 1,000-fold. DNA was
      extracted from carcass rinses and tetrathionate enrichments and used in PCR-ELISA
      for the detection of Campylobacter and S. enterica, respectively. With PCR-ELISA,
      Salmonella was detected in 20 of 120 (17%) chicken carcass rinses examined,
      without the inclusion of an enrichment step. Significant correlation was observed
      between PCR-ELISA and cultural methods (kappa = 0.83; chi-square test, P < 0.001)
      with only one false negative (1.67%) and four false positives (6.67%) when PCR
      ELISA was used to screen 60 tetrathionate enrichment cultures for Salmonella.
      With PCR-ELISA, we observed a positive correlation between the ELISA absorbance
      (optical density at 405 nm) and the campylobacter cell number in carcass rinse,
      as determined by standard culture methods. Overall, PCR-ELISA is a rapid and cost
      effective approach for the detection and enumeration of Salmonella and
      Campylobacter bacteria on poultry.

PMID- 12788756
TI  - Bacterial colonization of particles: growth and interactions.
AB  - Marine particles in the ocean are exposed to diverse bacterial communities, and
      colonization and growth of attached bacteria are important processes in the
      degradation and transformation of the particles. In an earlier study, we showed
      that the initial colonization of model particles by individual bacterial strains
      isolated from marine aggregates was a function of attachment and detachment. In
      the present study, we have investigated how this colonization process was further
      affected by growth and interspecific interactions among the bacteria. Long-term
      incubation experiments showed that growth dominated over attachment and
      detachment after a few hours in controlling the bacterial population density on
      agar particles. In the absence of grazing mortality, this growth led to an
      equilibrium population density consistent with the theoretical limit due to
      oxygen diffusion. Interspecific interaction experiments showed that the presence
      of some bacterial strains ("residents") on the agar particles either increased or
      decreased the colonization rate of other strains ("newcomers"). Comparison
      between an antibiotic-producing strain and its antibiotic-free mutant showed no
      inhibitory effect on the newcomers due to antibiotic production. On the contrary,
      hydrolytic activity of the antibiotic-producing strain appeared to benefit the
      newcomers and enhance their colonization rate. These results show that growth-
      and species-specific interactions have to be taken into account to adequately
      describe bacterial colonization of marine particles. Changes in colonization
      pattern due to such small-scale processes may have profound effects on the
      transformation and fluxes of particulate matter in the ocean.

PMID- 12788757
TI  - Use of growth indices from radiometric culture for quantification of sheep
      strains of Mycobacterium avium subsp. paratuberculosis.
AB  - A simple method for using growth indices from radiometric BACTEC cultures was
      evaluated for the enumeration of Australian sheep strains of Mycobacterium avium
      subsp. paratuberculosis. The numbers of viable organisms in inocula were
      determined by end-point titration in BACTEC cultures. Growth indices were
      measured by using a BACTEC 460 machine. There was a linear relationship between
      the number of days taken for the cumulative growth index to reach 1,000
      (dCGI1000) and log(10) inoculum size. The use of dCGI1000 was shown to be as
      effective as the use of growth index data from the entire growth cycle for the
      estimation of inoculum size. For particular isolates characterized by end-point
      titration, the dCGI1000 of a single BACTEC vial provided estimates of viable
      numbers within narrow prediction limits. Predictive relationships were also
      established for the enumeration of M. avium subsp. paratuberculosis from field
      samples by using the dCGI1000 of a single BACTEC vial, with prediction limits of
      +/-1 to 2 log units. Organisms from feces or contaminated soil grew more slowly
      than those from cultures or tissues, and separate equations were developed for
      enumeration from these sources.

PMID- 12788758
TI  - Chemical and biological interactions during nitrate and goethite reduction by
      Shewanella putrefaciens 200.
AB  - Although previous research has demonstrated that NO(3)(-) inhibits microbial
      Fe(III) reduction in laboratory cultures and natural sediments, the mechanisms of
      this inhibition have not been fully studied in an environmentally relevant medium
      that utilizes solid-phase, iron oxide minerals as a Fe(III) source. To study the
      dynamics of Fe and NO(3)(-) biogeochemistry when ferric (hydr)oxides are used as
      the Fe(III) source, Shewanella putrefaciens 200 was incubated under anoxic
      conditions in a low-ionic-strength, artificial groundwater medium with various
      amounts of NO(3)(-) and synthetic, high-surface-area goethite. Results showed
      that the presence of NO(3)(-) inhibited microbial goethite reduction more
      severely than it inhibited microbial reduction of the aqueous or microcrystalline
      sources of Fe(III) used in other studies. More interestingly, the presence of
      goethite also resulted in a twofold decrease in the rate of NO(3)(-) reduction, a
      10-fold decrease in the rate of NO(2)(-) reduction, and a 20-fold increase in the
      amounts of N(2)O produced. Nitrogen stable isotope experiments that utilized
      delta(15)N values of N(2)O to distinguish between chemical and biological
      reduction of NO(2)(-) revealed that the N(2)O produced during NO(2)(-) or NO(3)(
      ) reduction in the presence of goethite was primarily of abiotic origin. These
      results indicate that concomitant microbial Fe(III) and NO(3)(-) reduction
      produces NO(2)(-) and Fe(II), which then abiotically react to reduce NO(2)(-) to
      N(2)O with the subsequent oxidation of Fe(II) to Fe(III).

PMID- 12788759
TI  - Ecology of Vibrio vulnificus in estuarine waters of eastern North Carolina.
AB  - While several studies on the ecology of Vibrio vulnificus in Gulf Coast
      environments have been reported, there is little information on the distribution
      of this pathogen in East Coast waters. Thus, we conducted a multiyear study on
      the ecology of V. vulnificus in estuarine waters of the eastern United States,
      employing extensive multiple regression analyses to reveal the major
      environmental factors controlling the presence of this pathogen, and of Vibrio
      spp., in these environments. Monthly field samplings were conducted between July
      2000 and April 2002 at six different estuarine sites along the eastern coast of
      North Carolina. At each site, water samples were taken and nine physicochemical
      parameters were measured. V. vulnificus isolates, along with estuarine bacteria,
      Vibrio spp., Escherichia coli organisms, and total coliforms, were enumerated in
      samples from each site by using selective media. During the last 6 months of the
      study, sediment samples were also analyzed for the presence of vibrios, including
      V. vulnificus. Isolates were confirmed as V. vulnificus by using hemolysin gene
      PCR or colony hybridization. V. vulnificus was isolated only when water
      temperatures were between 15 and 27 degrees C, and its presence correlated with
      water temperature and dissolved oxygen and vibrio levels. Levels of V. vulnificus
      in sediments were low, and no evidence for an overwintering in this environment
      was found. Multiple regression analysis indicated that vibrio levels were
      controlled primarily by temperature, turbidity, and levels of dissolved oxygen,
      estuarine bacteria, and coliforms. Water temperature accounted for most of the
      variability in the concentrations of both V. vulnificus (47%) and Vibrio spp.
      (48%).

PMID- 12788760
TI  - Use of phospholipid fatty acids to detect previous self-heating events in stored
      peat.
AB  - The use of the phospholipid fatty acid (PLFA) composition of microorganisms to
      detect previous self-heating events was studied in naturally self-heated peat and
      in peat incubated under temperature-controlled conditions. An increased content
      of total PLFAs was found in self-heated peat compared to that in unheated peat.
      Two PLFAs, denoted T1 and T2, were detected only in the self-heated peat.
      Incubation of peat samples at 25 to 55 degrees C for 4 days indicated that T1 and
      T2 were produced from microorganisms with different optimum temperatures. This
      was confirmed by isolation of bacteria at 55 degrees C, which produced T2 but not
      T1. These bacteria produced another PLFA (denoted T3) which coeluted with
      18:1omega7. T2 and T3 were identified as omega-cyclohexyltridecanoic acid and
      omega-cyclohexylundecanoic acid, respectively, indicating that the bacteria
      belonged to the genus Alicyclobacillus: T1 was tentatively identified as omega
      cycloheptylundecanoic acid. T2 was detected 8 h after the peat incubation
      temperature was increased to 55 degrees C, and maximum levels were found within 5
      days of incubation. The PLFA 18:1omega7-T3 increased in proportion to T2. T1 was
      detected after 96 h at 55 degrees C, and its level increased throughout the
      incubation period, so that it eventually became one of the dominant PLFAs after
      80 days. In peat samples incubated at 55 degrees C and then at 25 degrees C, T1
      and T2 disappeared slowly. After 3 months, detectable levels were still found.
      Incubation at 25 degrees C after heating for 3 days at 55 degrees C decreased the
      amounts of T2 and 18:1omega7-T3 faster than did incubation at 5 degrees C. Thus,
      not only the duration and temperature during the heating event but also the
      storage temperature following heating are important for the detection of PLFAs
      indicating previous self-heating.

PMID- 12788761
TI  - Bacterial community structure and location in Stilton cheese.
AB  - The microbial diversity occurring in Stilton cheese was evaluated by 16S
      ribosomal DNA analysis with PCR-denaturing gradient gel electrophoresis. DNA
      templates for PCR experiments were directly extracted from the cheese as well as
      bulk cells harvested from a variety of viable-count media. The variable V3 and V4
      V5 regions of the 16S genes were analyzed. Closest relatives of Lactococcus
      lactis, Enterococcus faecalis, Lactobacillus plantarum, Lactobacillus curvatus,
      Leuconostoc mesenteroides, Staphylococcus equorum, and Staphylococcus sp. were
      identified by sequencing of the DGGE fragments. Fluorescently labeled
      oligonucleotide probes were developed to detect Lactococcus lactis, Lactobacillus
      plantarum, and Leuconostoc mesenteroides in fluorescence in situ hybridization
      (FISH) experiments, and their specificity for the species occurring in the
      community of Stilton cheese was checked in FISH experiments carried out with
      reference cultures. The combined use of these probes and the bacterial probe
      Eub338 in FISH experiments on Stilton cheese sections allowed the assessment of
      the spatial distribution of the different microbial species in the dairy matrix.
      Microbial colonies of bacteria showed a differential location in the different
      parts of the cheese examined: the core, the veins, and the crust. Lactococci were
      found in the internal part of the veins as mixed colonies and as single colonies
      within the core. Lactobacillus plantarum was detected only underneath the
      surface, while Leuconostoc microcolonies were homogeneously distributed in all
      parts observed. The combined molecular approach is shown to be useful to
      simultaneously describe the structure and location of the bacterial flora in
      cheese. The differential distribution of species found suggests specific
      ecological reasons for the establishment of sites of actual microbial growth in
      the cheese, with implications of significance in understanding the ecology of
      food systems and with the aim of achieving optimization of the fermentation
      technologies as well as preservation of traditional products.

PMID- 12788762
TI  - Molecular diversity of denitrifying genes in continental margin sediments within
      the oxygen-deficient zone off the Pacific coast of Mexico.
AB  - To understand the composition and structure of denitrifying communities in the
      oxygen-deficient zone off the Pacific coast of Mexico, the molecular diversity of
      nir genes from sediments obtained at four stations was examined by using a PCR
      based cloning approach. A total of 50 operational taxonomic units (OTUs) for nirK
      and 82 OTUs for nirS were obtained from all samples. Forty-four of the nirS
      clones and 31 of the nirK clones were sequenced; the levels of similarity of the
      nirS clones were 52 to 92%, and the levels of similarity of the nirS clones were
      50 to 99%. The percentages of overlapping OTUs between stations were 18 to 30%
      for nirS and 5 to 8% for nirK. Sequence analysis revealed that 26% of the nirS
      clones were related to the nirS genes of Alcaligenes faecalis (80 to 94% similar)
      and Pseudomonas stutzeri (80 to 99%), whereas 3 to 31% of the nirK clones were
      closely related to the nirK genes of Pseudomonas sp. strain G-179 (98 to 99%),
      Bradyrhizobium japonicum (91%), Blastobacter denitrificans (83%), and Alcaligenes
      xylosoxidans (96%). The rest of the clones, however, were less than 80% similar
      to nirS and nirK sequences available in sequence databases. The results of a
      principal-component analysis (PCA) based on the percentage of OTUs and
      biogeochemical data indicated that the nitrate concentration and oxygen have an
      effect on the denitrifying communities. The communities at the stations in oxygen
      deficient zones were more similar than the communities at the stations in the
      oxygenated zone. The denitrifying communities were more similar at the stations
      that were closer together and had similar nitrate levels. Also, the results of
      PCA based on biogeochemical properties suggest that geographic location and
      biogeochemical conditions, especially the nitrate and oxygen levels, appear to be
      the key factors that control the structure of denitrifying communities.

PMID- 12788763
TI  - Citrate synthase mutants of Sinorhizobium fredii USDA257 form ineffective nodules
      with aberrant ultrastructure.
AB  - The tricarboxylic acid (TCA) cycle plays an important role in generating the
      energy required by bacteroids to fix atmospheric nitrogen. Citrate synthase is
      the first enzyme that controls the entry of carbon into the TCA cycle. We cloned
      and determined the nucleotide sequence of the gltA gene that encodes citrate
      synthase in Sinorhizobium fredii USDA257, a symbiont of soybeans (Glycine max
      [L.] Merr.) and several other legumes. The deduced citrate synthase protein has a
      molecular weight of 48,198 and exhibits sequence similarity to citrate synthases
      from several bacterial species, including Sinorhizobium meliloti and Rhizobium
      tropici. Southern blot analysis revealed that the fast-growing S. fredii strains
      and Rhizobium sp. strain NGR234 contained a single copy of the gene located in
      the bacterial chromosome. S. fredii USDA257 gltA mutant HBK-CS1, which had no
      detectable citrate synthase activity, had diminished nodulation capacity and
      produced ineffective nodules on soybean. Light and electron microscopy
      observations revealed that the nodules initiated by HBK-CS1 contained very few
      bacteroids. The infected cells contained large vacuoles and prominent starch
      grains. Within the vacuoles, membrane structures that appeared to be reminiscent
      of disintegrating bacteroids were detected. The citrate synthase mutant had
      altered cell surface characteristics and produced three times more
      exopolysaccarides than the wild type produced. A plasmid carrying the USDA257
      gltA gene, when introduced into HBK-CS1, was able to restore all of the defects
      mentioned above. Our results demonstrate that a functional citrate synthase gene
      of S. fredii USDA257 is essential for efficient soybean nodulation and nitrogen
      fixation.

PMID- 12788764
TI  - Density-dependent sorting of physiologically different cells of Vibrio
      parahaemolyticus.
AB  - A pure bacterial culture is composed of clonal cells in different physiological
      states. Separation of those subpopulations is critical for further
      characterization and for understanding various processes in the cultured cells.
      We used density-dependent cell sorting with Percoll to separate subpopulations
      from cultures of a marine bacterium, Vibrio parahaemolyticus. Cells from cultures
      in the exponential and stationary phases were fractionated according to their
      buoyant density, and their culturability and ability to maintain culturability
      under low-temperature and low-nutrient stress (stress resistance) were
      determined. The buoyant density of the major portion of the cells decreased with
      culture age. The culturability of stationary-phase cells increased with
      increasing buoyant density, but that of exponential-phase cells did not. Stress
      resistance decreased with increasing buoyant density regardless of the growth
      phase. The results indicate that density-dependent cell sorting is useful for
      separating subpopulations of different culturabilities and stress resistances. We
      expect that this method will be a powerful tool for analyzing cells in various
      physiological states, such as the viable but nonculturable state.

PMID- 12788765
TI  - A C35 carotenoid biosynthetic pathway.
AB  - Upon coexpression with Erwinia geranylgeranyldiphosphate (GGDP) synthase in
      Escherichia coli, C(30) carotenoid synthase CrtM from Staphylococcus aureus
      produces novel carotenoids with the asymmetrical C(35) backbone. The products of
      condensation of farnesyldiphosphate and GDP, C(35) structures comprise 40 to 60%
      of total carotenoid accumulated. Carotene desaturases and carotene cyclases from
      C(40) or C(30) pathways accepted and converted the C(35) substrate, thus creating
      a C(35) carotenoid biosynthetic pathway in E. coli. Directed evolution to
      modulate desaturase step number, together with combinatorial expression of the
      desaturase variants with lycopene cyclases, allowed us to produce at least 10
      compounds not previously described. This result highlights the plastic and
      expansible nature of carotenoid pathways and illustrates how combinatorial
      biosynthesis coupled with directed evolution can rapidly access diverse chemical
      structures.

PMID- 12788766
TI  - Incidence and diversity of microorganisms within the walls of an active deep-sea
      sulfide chimney.
AB  - A large, intact sulfide chimney, designated Finn, was recovered from the Mothra
      Vent Field on the Juan de Fuca Ridge in 1998. Finn was venting 302 degrees C
      fluids on the seafloor and contained complex mineralogical zones surrounding a
      large open central conduit. Examination of microorganisms within these zones,
      followed by community analysis with oligonucleotide probes, showed that there
      were variations in the abundance and diversity of eubacteria and archaea from the
      exterior to the interior of the chimney. The microbial abundance based upon
      epifluorescence microscopy and quantitative fatty acid analyses varied from
      >10(8) cells/g of sulfide 2 to 10 cm within the chimney wall to <10(5) cells/g in
      interior zones. Direct microscopic observation indicated that microorganisms were
      attached to mineral surfaces throughout the structure. Whole-cell hybridization
      results revealed that there was a transition from a mixed community of eubacteria
      and archaea near the cool exterior of the chimney to primarily archaea near the
      warm interior. Archaeal diversity was examined in three zones of Finn by cloning
      and sequencing of the 16S rRNA gene. The majority of sequences from the exterior
      of the chimney were related to marine group I of the Crenarchaeota and uncultured
      Euryarchaeota from benthic marine environments. In contrast, clone libraries from
      interior regions of the chimney contained sequences closely related to
      methanogens, Thermococcales, and Archaeoglobales, in addition to uncultured
      crenarchaeal phylotypes obtained from deep subsurface sites. These observations
      of microbial communities within an active hydrothermal chimney provide insight
      into the microbial ecology within such structures and may facilitate follow-up
      exploration into expanding the known upper temperature limits of life.

PMID- 12788767
TI  - A rapid microtiter plate method to measure carbon dioxide evolved from carbon
      substrate amendments so as to determine the physiological profiles of soil
      microbial communities by using whole soil.
AB  - Sole-carbon-source tests (Biolog), designed to identify bacteria, have become
      very popular for metabolically fingerprinting soil microbial communities, despite
      disadvantages associated with the use of carbon source profiles that primarily
      select for fast-growing bacteria. In this paper we describe the use of an
      alternative method that combines the advantages of the Biolog community-level
      physiological profile (CLPP) method, in which microtiter-based detection plates
      are used, with the ability to measure carbon dioxide evolution from whole soil.
      This method facilitates measurement over short periods of time (4 to 6 h) and
      does not require the extraction and culturing of organisms. Deep-well microtiter
      plates are used as test wells into which soil is placed. The apparatus to fill
      the deep-well plates and interface it with a second removable detection plate is
      described. Two detection systems, a simple colorimetric reaction in absorbent
      alkali and scintillation counting with radioactive carbon sources, are described.
      The methods were compared to the Biolog-CLPP system by using soils under
      different vegetation types and soil treated with wastewater sludge. We aimed to
      test the hypothesis that using whole soil would have specific advantages over
      using extracts in that more immediate responses to substrates could be obtained
      that would reflect activity rather than growth. The whole-soil method was more
      rapid and gave earlier detection of C source use. Also, the metabolic
      fingerprints obtained could discriminate between sludge treatments.

PMID- 12788768
TI  - Development and application of an assay for uranyl complexation by fungal
      metabolites, including siderophores.
AB  - An assay to detect UO(2)(2+) complexation was developed based on the chrome
      azurol S (CAS) assay for siderophores (B. Schwyn and J. B. Neilands, Anal.
      Biochem. 160:47-56, 1987) and was used to investigate the ability of fungal
      metabolites to complex actinides. In this assay the discoloration of two dyed
      agars (one containing a CAS-Fe(3+) dye and the other containing a CAS-UO(2)(2+)
      dye) caused by ligands was quantified. The assay was tested by using the
      siderophore desferrioxamine B (DFO), and the results showed that there was a
      regular, reproducible relationship between discoloration and the amount of
      siderophore added. The ratio of the discoloration on the CAS-UO(2)(2+) agar to
      the discoloration on the CAS-Fe(3+) agar was independent of the amount of
      siderophore added. A total of 113 fungi and yeasts were isolated from three soil
      samples taken from the Peak District National Park. The fungi were screened for
      the production of UO(2)(2+) chelators by using the CAS-based assay and were also
      tested specifically for hydroxamate siderophore production by using the
      hydroxamate siderophore auxotroph Aureobacterium flavescens JG-9. This organism
      is highly sensitive to the presence of hydroxamate siderophores. However, the CAS
      based assay was found to be less sensitive than the A. flavescens JG-9 assay. No
      significant difference between the results for each site for the two tests was
      found. Three isolates were selected for further study and were identified as two
      Pencillium species and a Mucor species. Our results show that the new assay can
      be effectively used to screen fungi for the production of UO(2)(2+) chelating
      ligands. We suggest that hydroxamate siderophores can be produced by mucoraceous
      fungi.

PMID- 12788769
TI  - Combining culture-dependent and -independent methodologies for estimation of
      richness of estuarine bacterioplankton consuming riverine dissolved organic
      matter.
AB  - Three different methods for analyzing natural microbial community diversity were
      combined to maximize an estimate of the richness of bacterioplankton catabolizing
      riverine dissolved organic matter (RDOM). We also evaluated the ability of
      culture-dependent quantitative DNA-DNA hybridization, a 16S rRNA gene clone
      library, and denaturing gradient gel electrophoresis (DGGE) to detect bacterial
      taxa in the same sample. Forty-two different cultivatable strains were isolated
      from rich and poor solid media. In addition, 50 unique clones were obtained by
      cloning of the bacterial 16S rDNA gene amplified by PCR from the community DNA
      into an Escherichia coli vector. Twenty-three unique bands were sequenced from 12
      DGGE profiles, excluding a composite fuzzy band of the Cytophaga-Flavobacterium
      group. The different methods gave similar distributions of taxa at the genus
      level and higher. However, the match at the species level among the methods was
      poor, and only one species was identified by all three methods. Consequently, all
      three methods identified unique subsets of bacterial species, amounting to a
      total richness of 97 operational taxonomic units in the experimental system. The
      confidence in the results was, however, dependent on the current precision of the
      phylogenetic determination and definition of the species. Bacterial consumers of
      RDOM in the studied estuary were primarily both cultivatable and uncultivable
      taxa of the Cytophaga-Flavobacterium group, a concordant result among the methods
      applied. Culture-independent methods also suggested several not-yet-cultivated
      beta-proteobacteria to be RDOM consumers.

PMID- 12788770
TI  - Mapping of genomic regions (quantitative trait loci) controlling production and
      quality in industrial cultures of the edible basidiomycete Pleurotus ostreatus.
AB  - Industrial production of the edible basidiomycete Pleurotus ostreatus (oyster
      mushroom) is based on a solid fermentation process in which a limited number of
      selected strains are used. Optimization of industrial mushroom production depends
      on improving the culture process and breeding new strains with higher yields and
      productivities. Traditionally, fungal breeding has been carried out by an
      empirical trial and error process. In this study, we used a different approach by
      mapping quantitative trait loci (QTLs) controlling culture production and quality
      within the framework of the genetic linkage map of P. ostreatus. Ten production
      traits and four quality traits were studied and mapped. The production QTLs
      identified explain nearly one-half of the production variation. More
      interestingly, a single QTL mapping to the highly polymorphic chromosome VII
      appears to be involved in control of all the productivity traits studied. Quality
      QTLs appear to be scattered across the genome and to have less effect on the
      variation of the corresponding traits. Moreover, some of the new hybrid strains
      constructed in the course of our experiments had production or quality values
      higher than those of the parents or other commercial strains. This approach opens
      the possibility of marker-assisted selection and breeding of new industrial
      strains of this fungus.

PMID- 12788771
TI  - Characterization of an autotrophic nitrogen-removing biofilm from a highly loaded
      lab-scale rotating biological contactor.
AB  - In this study, a lab-scale rotating biological contactor (RBC) treating a
      synthetic NH(4)(+) wastewater devoid of organic carbon and showing high N losses
      was examined for several important physiological and microbial characteristics.
      The RBC biofilm removed 89% +/- 5% of the influent N at the highest surface load
      of approximately 8.3 g of N m(-2) day(-1), with N(2) as the main end product. In
      batch tests, the RBC biomass showed good aerobic and anoxic ammonium oxidation
      (147.8 +/- 7.6 and 76.5 +/- 6.4 mg of NH(4)(+)-N g of volatile suspended solids
      [VSS](-1) day(-1), respectively) and almost no nitrite oxidation (< 1 mg of N g
      of VSS(-1) day(-1)). The diversity of aerobic ammonia-oxidizing bacteria (AAOB)
      and planctomycetes in the biofilm was characterized by cloning and sequencing of
      PCR-amplified partial 16S rRNA genes. Phylogenetic analysis of the clones
      revealed that the AAOB community was fairly homogeneous and was dominated by
      Nitrosomonas-like species. Close relatives of the known anaerobic ammonia
      oxidizing bacterium (AnAOB) Kuenenia stuttgartiensis dominated the planctomycete
      community and were most probably responsible for anoxic ammonium oxidation in the
      RBC. Use of a less specific planctomycete primer set, not amplifying the AnAOB,
      showed a high diversity among other planctomycetes, with representatives of all
      known groups present in the biofilm. The spatial organization of the biofilm was
      characterized using fluorescence in situ hybridization (FISH) with confocal
      scanning laser microscopy (CSLM). The latter showed that AAOB occurred side by
      side with putative AnAOB (cells hybridizing with probe PLA46 and AMX820/KST1275)
      throughout the biofilm, while other planctomycetes hybridizing with probe PLA886
      (not detecting the known AnAOB) were present as very conspicuous spherical
      structures. This study reveals that long-term operation of a lab-scale RBC on a
      synthetic NH(4)(+) wastewater devoid of organic carbon yields a stable biofilm in
      which two bacterial groups, thought to be jointly responsible for the high
      autotrophic N removal, occur side by side throughout the biofilm.

PMID- 12788772
TI  - Microbial reduction and precipitation of vanadium by Shewanella oneidensis.
AB  - Shewanella oneidensis couples anaerobic oxidation of lactate, formate, and
      pyruvate to the reduction of vanadium pentoxide (V(V)). The bacterium reduces
      V(V) (vanadate ion) to V(IV) (vanadyl ion) in an anaerobic atmosphere. The
      resulting vanadyl ion precipitates as a V(IV)-containing solid.

PMID- 12788774
TI  - Characterization of the first molluscicidal lipopolysaccharide from Moraxella
      osloensis.
AB  - Moraxella osloensis is a bacterium that is mutualistically associated with
      Phasmarhabditis hermaphrodita, a nematode that has potential for the biocontrol
      of mollusk pests, especially the slug Deroceras reticulatum. We discovered that
      purified M. osloensis lipopolysaccharide (LPS) possesses a lethal toxicity to D.
      reticulatum when administered by injection but no contact or oral toxicity to
      this slug. The toxicity of the LPS resides in the lipid A moiety. M. osloensis
      LPS was semiquantitated at 6 x 10(7) endotoxin units per mg. The LPS is a rough
      type LPS with an estimated molecular weight of 5,300. Coinjection of
      galactosamine with the LPS increased the LPS's toxicity to the slug two- to four
      fold. The galactosamine-induced sensitization of the slug to the LPS was reversed
      completely by uridine.

PMID- 12788773
TI  - Adhesion, invasion, and translocation characteristics of Listeria monocytogenes
      serotypes in Caco-2 cell and mouse models.
AB  - Adhesion is a crucial first step in Listeria monocytogenes pathogenesis. In this
      study, we examined how the adhesion properties of serotypes correlate with their
      invasion efficiencies in a cell culture model (Caco-2) and in a mouse model.
      Adhesion characteristics of all 13 serotypes of L. monocytogenes (25 strains)
      were analyzed, which yielded three distinct groups (P < 0.05) with high-, medium
      , and low-level-adhesion profiles. The efficiency of these strains in invading
      the Caco-2 cell line was analyzed, which produced two groups; however, the
      overall correlation (R(2)) was only 0.1236. In the mouse bioassay, all selected
      strains, irrespective of their adhesion profiles, translocated to the liver and
      the spleen with almost equal frequencies that did not show any clear relationship
      with adhesion profiles. However, the serotypes with increased adhesion showed a
      slightly increased translocation to the brain (R(2) = 0.3371). Collectively,
      these results indicate that an in vitro adhesion profile might not be an accurate
      assessment of a strain's ability to invade a cultured cell line or organs or
      tissues in a mouse model.

PMID- 12788775
TI  - Alkylphenol biotransformations catalyzed by 4-ethylphenol methylenehydroxylase.
AB  - 4-ethylphenol methylenehydroxylase from Pseudomonas putida JD1 acts by
      dehydrogenation of its substrate to give a quinone methide, which is then
      hydrated to an alcohol. It was shown to be active with a range of 4-alkylphenols
      as substrates. 4-n-propylphenol, 4-n-butylphenol, chavicol, and 4
      hydroxydiphenylmethane were hydroxylated on the methylene group next to the
      benzene ring and produced the corresponding chiral alcohol as the major product.
      The alcohols 1-(4'-hydroxyphenyl)propanol and 1-(4'-hydroxyphenyl)-2-propen-1-ol,
      produced by the biotransformation of 4-n-propylphenol and chavicol, respectively,
      were shown to be R(+) enantiomers. 5-Indanol, 6-hydroxytetralin, 4
      isopropylphenol, and cyclohexylphenol, with cyclic or branched alkyl groups, gave
      the corresponding vinyl compounds as their major products.

PMID- 12788776
TI  - On the origins of cyanuric acid hydrolase: purification, substrates, and
      prevalence of AtzD from Pseudomonas sp. strain ADP.
AB  - Cyanuric acid hydrolase (AtzD) from Pseudomonas sp. strain ADP was purified to
      homogeneity. Of 22 cyclic amides and triazine compounds tested, only cyanuric
      acid and N-methylisocyanuric acid were substrates. Other cyclic amidases were
      found not to hydrolyze cyanuric acid. Ten bacteria that use cyanuric acid as a
      sole nitrogen source for growth were found to contain either atzD or trzD, but
      not both genes.

PMID- 12788778
TI  - Linkage of high rates of sulfate reduction in Yellowstone hot springs to unique
      sequence types in the dissimilatory sulfate respiration pathway.
AB  - Diversity, habitat range, and activities of sulfate-reducing prokaryotes within
      hot springs in Yellowstone National Park were characterized using endogenous
      activity measurements, molecular characterization, and enrichment. Five major
      phylogenetic groups were identified using PCR amplification of the dissimilatory
      sulfite reductase genes (dsrAB) from springs demonstrating significant sulfate
      reduction rates, including a warm, acidic (pH 2.5) stream and several nearly
      neutral hot springs with temperatures reaching 89 degrees C. Three of these
      sequence groups were unrelated to named lineages, suggesting that the diversity
      and habitat range of sulfate-reducing prokaryotes exceeds that now represented in
      culture.

PMID- 12788777
TI  - Phylogeny and characterization of three nifH-homologous genes from Paenibacillus
      azotofixans.
AB  - In this paper, we report the cloning and characterization of three Paenibacillus
      azotofixans DNA regions containing genes involved in nitrogen fixation.
      Sequencing analysis revealed the presence of nifB1H1D1K1 gene organization in the
      4,607-bp SacI DNA fragment. This is the first report of linkage of a nifB open
      reading frame upstream of the structural nif genes. The second (nifB2H2) and
      third (nifH3) nif homologues are confined within the 6,350-bp HindIII and 2,840
      bp EcoRI DNA fragments, respectively. Phylogenetic analysis demonstrated that
      NifH1 and NifH2 form a monophyletic group among cyanobacterial NifH proteins.
      NifH3, on the other hand, clusters among NifH proteins of the highly divergent
      methanogenic archaea.

PMID- 12788779
TI  - Behavior of psychrotrophic lactic acid bacteria isolated from spoiling cooked
      meat products.
AB  - Three kinds of lactic acid bacteria were isolated from spoiling cooked meat
      products stored below 10 degrees C. They were identified as Leuconostoc
      mesenteroides subsp. mesenteroides, Lactococcus lactis subsp. lactis, and
      Leuconostoc citreum. All three strains grew well in MRS broth at 10 degrees C. In
      particular, L. mesenteroides subsp. mesenteroides and L. citreum grew even at 4
      degrees C, and their doubling times were 23.6 and 51.5 h, respectively. On the
      other hand, although the bacteria were initially below the detection limit (<10
      CFU/g) in model cooked meat products, the bacterial counts increased to 10(8)
      CFU/g at 10 degrees C after 7 to 12 days.

PMID- 12788780
TI  - Microorganisms associated with uranium bioremediation in a high-salinity
      subsurface sediment.
AB  - Although stimulation of dissimilatory metal reduction to promote the reductive
      precipitation of uranium has been shown to successfully remove uranium from some
      aquifer sediments, the organisms in the family Geobacteraceae that have been
      found to be associated with metal reduction in previous studies are not known to
      grow at the high salinities found in some uranium-contaminated groundwaters.
      Studies with a highly saline uranium-contaminated aquifer sediment demonstrated
      that the addition of acetate could stimulate the removal of U(VI) from the
      groundwater. This removal was associated with an enrichment in microorganisms
      most closely related to Pseudomonas and Desulfosporosinus species.

PMID- 12788781
TI  - Direct detection of Vibrio cholerae and ctxA in Peruvian coastal water and
      plankton by PCR.
AB  - Seawater and plankton samples were collected over a period of 17 months from
      November 1998 to March 2000 along the coast of Peru. Total DNA was extracted from
      water and from plankton grouped by size into two fractions (64 micro m to 202
      micro m and >202 micro m). All samples were assayed for Vibrio cholerae, V.
      cholerae O1, V. cholerae O139, and ctxA by PCR. Of 50 samples collected and
      tested, 33 (66.0%) were positive for V. cholerae in at least one of the three
      fractions. Of these, 62.5% (n = 32) contained V. cholerae O1; ctxA was detected
      in 25% (n = 20) of the V. cholerae O1-positive samples. None were positive for V.
      cholerae O139. Thus, PCR was successfully employed in detecting toxigenic V.
      cholerae directly in seawater and plankton samples and provides evidence for an
      environmental reservoir for this pathogen in Peruvian coastal waters.

PMID- 12788782
TI  - Generation of food-grade lactococcal starters which produce the lantibiotics
      lacticin 3147 and lacticin 481.
AB  - Transconjugant lactococcal starters which produce both lantibiotics lacticin 3147
      and lacticin 481 were generated via conjugation of large bacteriocin-encoding
      plasmids. A representative of one of the resultant strains proved more effective
      at killing Lactobacillus fermentum and inhibiting the growth of Listeria
      monocytogenes LO28H than either of the single bacteriocin-producing parental
      strains, demonstrating the potential of these transconjugants as protection
      cultures for food safety applications.

PMID- 12788783
TI  - Proteolysis, the ubiquitin-proteasome system, and renal diseases.
AB  - Protein degradation is a critical process for the growth and function of cells.
      Proteolysis eliminates abnormal proteins, controls many cellular regulatory
      processes, and supplies amino acids for cellular remodeling. When substrates of
      proteolytic pathways are poorly recognized or there is mistiming of proteolysis,
      profound changes in cell function can occur. Based on these potential problems,
      it is not surprising that alterations in proteolytic enzymes/cofactors or in the
      structure of protein substrates that render them more or less susceptible to
      degradation are responsible for disorders associated with kidney cell
      malfunctions. Multiple pathways exist for protein degradation. The best-described
      proteolytic system is the ubiquitin-proteasome pathway, which requires ATP and
      degrades the bulk of cellular and some membrane proteins. This review will survey
      examples of renal abnormalities that are associated with defective protein
      degradation involving the ubiquitin-proteasome pathway. Loss of muscle mass
      associated with chronic renal failure, von Hippel-Lindau disease, Liddle
      syndrome, and ischemic acute renal failure will be discussed. These examples are
      indicative of the diverse roles of the ubiquitin-proteasome system in renal
      associated pathological conditions.

PMID- 12788784
TI  - Iron, lipocalin, and kidney epithelia.
AB  - Brilliant new discoveries in the field of iron metabolism have revealed novel
      transmembrane iron transporters, novel hormones that regulate iron traffic, and
      iron's control of gene expression. An important role for iron in the embryonic
      kidney was first identified by Ekblom, who studied transferrin (Landschulz W and
      Ekblom P. J Biol Chem 260: 15580-15584, 1985; Landschulz W, Thesleff I, and
      Ekblom P. J Cell Biol 98: 596-601, 1984; Thesleff I, Partanen AM, Landschulz W,
      Trowbridge IS, and Ekblom P. Differentiation 30: 152- 158, 1985). Nevertheless,
      how iron traffics to developing organs remains obscure. This review discusses a
      member of the lipocalin superfamily, 24p3 or neutrophil gelatinase-associated
      lipocalcin (NGAL), which induces the formation of kidney epithelia. We review the
      data showing that lipocalins transport low-molecular-weight chemical signals and
      data indicating that 24p3/NGAL transports iron. We compare 24p3/NGAL to
      transferrin and a variety of other iron trafficking pathways and suggest specific
      roles for each in iron transport.

PMID- 12788785
TI  - Appetizing rancidity of apoptotic cells for macrophages: oxidation,
      externalization, and recognition of phosphatidylserine.
AB  - Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted
      or irreparably damaged cells ultimately leading to their orderly phagocytosis in
      the absence of calamitous inflammatory responses. Recent studies have
      demonstrated that the generation of free radical intermediates and subsequent
      oxidative stress are implicated as part of the apoptotic execution process.
      Oxidative stress may simply be an unavoidable yet trivial byproduct of the
      apoptotic machinery; alternatively, intermediates or products of oxidative stress
      may act as essential signals for the execution of the apoptotic program. This
      review is focused on the specific role of oxidative stress in apoptotic
      signaling, which is realized via phosphatidylserine-dependent pathways leading to
      recognition of apoptotic cells and their effective clearance. In particular, the
      mechanisms involved in selective phosphatidylserine oxidation in the plasma
      membrane during apoptosis and its association with disturbances of phospholipid
      asymmetry leading to phosphatidylserine externalization and recognition by
      macrophage receptors are at the center of our discussion. The putative importance
      of this oxidative phosphatidylserine signaling in lung physiology and disease are
      also discussed.

PMID- 12788786
TI  - Acute lung injury and predictors of mortality.

PMID- 12788787
TI  - Allergic asthma in mice: what determines the phenotype?

PMID- 12788788
TI  - Role of CaM kinase II and ERK activation in thrombin-induced endothelial cell
      barrier dysfunction.
AB  - We have previously shown that thrombin-induced endothelial cell barrier
      dysfunction involves cytoskeletal rearrangement and contraction, and we have
      elucidated the important role of endothelial cell myosin light chain kinase and
      the actin- and myosin-binding protein caldesmon. We evaluated the contribution of
      calmodulin (CaM) kinase II and extracellular signal-regulated kinase (ERK)
      activation in thrombin-mediated bovine pulmonary artery endothelial cell
      contraction and barrier dysfunction. Similar to thrombin, infection with a
      constitutively active adenoviral alpha-CaM kinase II construct induced
      significant ERK activation, indicating that CaM kinase II activation lies
      upstream of ERK. Thrombin-induced ERK-dependent caldesmon phosphorylation
      (Ser789) was inhibited by either KN-93, a specific CaM kinase II inhibitor, or
      U0126, an inhibitor of MEK activation. Immunofluorescence microscopy studies
      revealed phosphocaldesmon colocalization within thrombin-induced actin stress
      fibers. Pretreatment with either U0126 or KN-93 attenuated thrombin-mediated
      cytoskeletal rearrangement and evoked declines in transendothelial electrical
      resistance while reversing thrombin-induced dissociation of myosin from
      nondenaturing caldesmon immunoprecipitates. These results strongly suggest the
      involvement of CaM kinase II and ERK activities in thrombin-mediated caldesmon
      phosphorylation and both contractile and barrier regulation.

PMID- 12788789
TI  - STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation.
AB  - Interferon-gamma (IFN-gamma) is required for induction of the human nitric oxide
      synthase-2 (NOS2) gene in lung epithelium. Although the human NOS2 promoter
      region contains many cytokine-responsive elements, the molecular basis of
      induction is only partially understood. Here, the major cis-regulatory elements
      that control IFN-gamma-inducible NOS2 gene transcription in human lung epithelial
      cells are identified as composite response elements that bind signal transducer
      and activator of transcription 1 (STAT-1) and activator protein 1 (AP-1), which
      is comprised of c-Fos, Fra-2, c-Jun, and JunD. Notably, IFN-gamma activation of
      the human NOS2 promoter is shown to require functional AP-1 regulatory region(s),
      suggesting a role for AP-1 activation/binding in the IFN-gamma induction of
      genes. We show that c-Fos interacts with STAT-1 after IFN-gamma activation and
      the c-Fos/STAT-1 complex binds to the gamma-activated site (GAS) element in close
      proximity to AP-1 sites located at 4.9 kb upstream of the transcription start
      site. Taken together, our findings support a model in which a physical
      interaction between c-Fos and STAT-1 participates in NOS2 gene transcriptional
      activation.

PMID- 12788790
TI  - Monitoring CML after nonmyeloablative transplantations: how negative is negative?

PMID- 12788791
TI  - Rapid identification of CBFB-MYH11-positive acute myeloid leukemia (AML) cases by
      one single MYH11 real-time RT-PCR.

PMID- 12788792
TI  - No exon 4 polymorphism of cytochrome P450 CYP2C9 in Taiwanese.

PMID- 12788793
TI  - Lack of alteration in GATA-1 expression in CD34+ hematopoietic progenitors from
      patients with idiopathic myelofibrosis.

PMID- 12788794
TI  - Deferiprone and hepatic fibrosis.

PMID- 12788795
TI  - Donor serostatus and CMV infection and disease among recipients of prophylactic
      granulocyte transfusions.

PMID- 12788796
TI  - Cardiovascular endocrinology: introduction.

PMID- 12788798
TI  - Newly recognized components of the renin-angiotensin system: potential roles in
      cardiovascular and renal regulation.
AB  - The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the
      control of cardiovascular, renal, and adrenal function that governs body fluid
      and electrolyte balance, as well as arterial pressure. The classical RAS consists
      of a circulating endocrine system in which the principal effector hormone is
      angiotensin (ANG) II. ANG is produced by the action of renin on angiotensinogen
      to form ANG I and its subsequent conversion to the biologically active
      octapeptide by ANG-converting enzyme. ANG II actions are mediated via the ANG
      type 1 receptor. Here, we discuss recent advances in our understanding of the
      components and actions of the RAS, including local tissue RASs, a renin receptor,
      ANG-converting enzyme-2, ANG (1-7), the function of the ANG type 2 receptor, and
      ANG receptor heterodimerization. The role of the RAS in the regulation of
      cardiovascular and renal function is reviewed and discussed in light of these
      newly recognized components.

PMID- 12788799
TI  - Cardiovascular function in acromegaly.
AB  - Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase
      in mortality, mainly from vascular disease, which is probably a result of the
      long exposure of tissues to excess GH before diagnosis and treatment. There is
      accumulating evidence that effective treatment to lower serum GH levels to less
      than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I
      improves long-term outcome and survival. In addition to recognized cardiovascular
      risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there
      is accumulating evidence of specific structural and functional changes in the
      heart in acromegaly. Along with endothelial dysfunction, these changes may
      contribute to the increased mortality in this disease. There are specific
      structural changes in the myocardium with increased myocyte size and interstitial
      fibrosis of both ventricles. Left ventricular hypertrophy is common even in young
      patients with short duration of disease. Some of these structural changes can be
      reversed by effective treatment. Functionally, the main consequence of these
      changes is impaired left ventricular diastolic function, particularly when
      exercising, such that exercise tolerance is reduced. Diastolic function improves
      with treatment, but the effect on exercise tolerance is more variable, and more
      longitudinal data are required to assess the benefits. What scant data there are
      on rhythm changes suggest an increase in complex ventricular arrhythmias,
      possibly as a result of the disordered left ventricular architecture. The
      functional consequences of these changes are unclear, but they may provide a
      useful early marker for the ventricular remodeling that occurs in the acromegalic
      heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early
      marker of atherosclerosis, and limited data imply that this is impaired in active
      acromegaly and can be improved with treatment. Similarly, early arterial
      structural changes, such as thickened intima media layer, appear more common in
      acromegalics, and there are hints that this may diminish with effective
      treatment, although more studies are required for a definite conclusion on this
      topic. In conclusion, impaired cardiac and endothelial structure and function in
      acromegaly are risk factors for vascular mortality and should be regarded as
      legitimate therapeutic targets in the overall management of this condition.

PMID- 12788800
TI  - Insulin resistance and chronic cardiovascular inflammatory syndrome.
AB  - Insulin resistance is increasingly recognized as a chronic, low-level,
      inflammatory state. Hyperinsulinemia and insulin action were initially proposed
      as the common preceding factors of hypertension, low high-density lipoprotein
      cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose
      tolerance, linking all these abnormalities to the development of coronary heart
      disease. The similarities of insulin resistance with another inflammatory state,
      atherosclerosis, have been described only in the last few decades.
      Atherosclerosis and insulin resistance share similar pathophysiological
      mechanisms, mainly due to the actions of the two major proinflammatory cytokines,
      TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of
      these cytokines is associated with metabolic derangement and simultaneously with
      coronary heart disease. Dysregulation of the inflammatory axis predicts the
      development of insulin resistance and type 2 diabetes mellitus. The knowledge of
      how interactions between metabolic and inflammatory pathways occur will be useful
      in future therapeutic strategies. The effective administration of
      antiinflammatory agents in the treatment of insulin resistance and
      atherosclerosis is only the beginning of a promising approach in the management
      of these syndromes.

PMID- 12788801
TI  - Polycystic ovary syndrome and cardiovascular disease: a premature association?
AB  - Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at
      increased risk for cardiovascular disease (CVD), given the high prevalence of the
      metabolic syndrome X among them. There is, however, no single definition of PCOS,
      and for that reason a comparison of studies that have analyzed its association
      with CVD is compromised from the start. Long-term studies of well characterized
      women with PCOS are lacking, and the link to primary cardiovascular events such
      as stroke or myocardial infarction remains more speculative than substantive.
      Epidemiological studies that have focused on isolated signs and stigmata of PCOS,
      such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found
      mixed results. There are studies that suggest a slight increase in cardiovascular
      events in women with polycystic ovaries, with perhaps stronger evidence between
      an increased risk of cardiovascular events in women with menstrual irregularity.
      However, there is little evidence for an association between hyperandrogenism per
      se and cardiovascular events. Furthermore, there are less data to substantiate an
      increased risk of events in women with PCOS identified on the basis of a
      combination of signs and symptoms, such as hyperandrogenic chronic anovulation.
      The existing data suggest that PCOS may adversely affect or accelerate the
      development of an adverse cardiovascular risk profile, and even of subclinical
      signs of atherosclerosis, but it does not appear to lower the age of clinical
      presentation to a premenopausal age group. Future studies to identify the risk of
      cardiovascular events in women with PCOS will benefit from clear and extensive
      phenotyping of PCOS abnormalities at baseline, from a prospective design, from
      larger sample sizes, and from longer follow-up.

PMID- 12788802
TI  - Androgens and cardiovascular disease.
AB  - Globally, cardiovascular disease will continue causing most human deaths for the
      foreseeable future. The consistent gender gap in life span of approximately 5.6
      yr in all advanced economies must derive from gender differences in age-specific
      cardiovascular death rates, which rise steeply in parallel for both genders but 5
      10 yr earlier in men. The lack of inflection point at modal age of menopause,
      contrasting with unequivocally estrogen-dependent biological markers like breast
      cancer or bone density, makes estrogen protection of premenopausal women an
      unlikely explanation. Limited human data suggest that testosterone exposure does
      not shorten life span in either gender, and oral estrogen treatment increases
      risk of cardiovascular death in men as it does in women. Alternatively, androgen
      exposure in early life (perinatal androgen imprinting) may predispose males to
      earlier onset of atherosclerosis. Following the recent reevaluation of the
      estrogen-protection orthodoxy, empirical research has flourished into the role of
      androgens in the progression of cardiovascular disease, highlighting the need to
      better understand androgen receptor (AR) coregulators, nongenomic androgen
      effects, tissue-specific metabolic activation of androgens, and androgen
      sensitivity. Novel therapeutic targets may arise from understanding how androgens
      enhance early plaque formation and cause vasodilatation via nongenomic androgen
      effects on vascular smooth muscle, and how tissue-specific variations in androgen
      effects are modulated by AR coregulators as well as metabolic activation of
      testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting
      on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor
      alpha/beta) the biological effects of testosterone on the vasculature.
      Observational studies show that blood testosterone concentrations are
      consistently lower among men with cardiovascular disease, suggesting a possible
      preventive role for testosterone therapy, which requires critical evaluation by
      further prospective studies. Short-term interventional studies show that
      testosterone produces a modest but consistent improvement in cardiac ischemia
      over placebo, comparable to the effects of existing antianginal drugs. By
      contrast, testosterone therapy has no beneficial effects in peripheral arterial
      disease but has not been evaluated in cerebrovascular disease. Erectile
      dysfunction is most frequently caused by pelvic arterial insufficiency due to
      atherosclerosis, and its sentinel relationship to generalized atherosclerosis is
      insufficiently appreciated. The commonality of risk factor patterns and
      mechanisms (including endothelial dysfunction) suggests that the efficacy of
      antiatherogenic therapy is an important challenge with the potential to enhance
      men's motivation for prevention and treatment of cardiovascular diseases.

PMID- 12788803
TI  - Cardiac hormones as diagnostic tools in heart failure.
AB  - In patients with heart failure, plasma levels of atrial natriuretic peptide
      (ANP), B-type natriuretic peptide (BNP), and the N-terminal fragments of their
      prohormones (N-ANP and N-BNP) are elevated, because the cardiac hormonal system
      is activated by increased wall stretch due to increased volume and pressure
      overload. Patients suspected of having heart failure can be selected for further
      investigations on the basis of having an elevated plasma concentration of N-ANP,
      BNP, and N-BNP. High levels of cardiac hormones identify those at greatest risk
      for future serious cardiovascular events. Moreover, adjusting heart failure
      treatment to reduce plasma levels of N-BNP may improve outcome. Cardiac hormones
      are most useful clinically as a rule-out test. In acutely symptomatic patients, a
      very high negative predictive value is coupled with a relatively high positive
      predictive value. Measurement of cardiac hormones in patients with heart failure
      may reduce the need for hospitalizations and for more expensive investigations
      such as echocardiography. However, there have also been conflicting reports on
      the diagnostic value of cardiac hormones, they are not specific for any disease,
      and the magnitude of the effects of age and gender on BNP in the normal subgroup
      suggests that these parameters need to be considered when interpreting cardiac
      hormone levels.

PMID- 12788806
TI  - Heteroexchange of purines in the hippocampus: mixing-up or messing-up ATP and
      adenosine.

PMID- 12788804
TI  - The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism
      of endocrine and other tissues.
AB  - Because cholesterol is a precursor for the synthesis of steroid hormones,
      steroidogenic tissues have evolved multiple pathways to ensure adequate supplies
      of cholesterol. These include synthesis, storage as cholesteryl esters, and
      import from lipoproteins. In addition to endocytosis via members of the low
      density lipoprotein receptor superfamily, steroidogenic cells acquire cholesterol
      from lipoproteins by selective lipid uptake. This pathway, which does not involve
      lysosomal degradation of the lipoprotein, is mediated by the scavenger receptor
      class B type I (SR-BI). SR-BI is highly expressed in steroidogenic cells, where
      its expression is regulated by various trophic hormones, as well as in the liver.
      Studies of genetically manipulated strains of mice have established that SR-BI
      plays a key role in regulating lipoprotein metabolism and cholesterol transport
      to steroidogenic tissues and to the liver for biliary secretion. In addition,
      analysis of SR-BI-deficient mice has shown that SR-BI expression is important for
      alpha-tocopherol and nitric oxide metabolism, as well as normal red blood cell
      maturation and female fertility. These mouse models have also revealed that SR-BI
      can protect against atherosclerosis. If SR-BI plays similar physiological and
      pathophysiological roles in humans, it may be an attractive target for
      therapeutic intervention in cardiovascular and reproductive diseases.

PMID- 12788807
TI  - A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human
      nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling
      pathway.
AB  - (1) We examined A3 adenosine and CB1 cannabinoid receptor-coupled signaling
      pathways regulating Cl(-) current in a human nonpigmented ciliary epithelial
      (NPCE) cell line. (2) Whole-cell patch-clamp recordings demonstrated that the A3
      receptor agonist, IB-MECA, activates an outwardly rectifying Cl(-)current
      (I(Cl,Aden)) in NPCE cells, which was inhibited by the adenosine receptor
      antagonist, CGS-15943 or by the protein kinase C (PKC) activator, phorbol 12,13
      dibutyrate (PDBu). (3) Treatment of NPCE cells with pertussis-toxin (PTX), or
      transfection with the COOH-terminus of beta-adrenergic receptor kinase (ct
      betaARK), inhibited I(Cl,Aden). The phosphatidyl inositol 3-kinase (PI3K)
      inhibitor, wortmannin, had no effect on I(Cl,Aden); however, the mitogen
      activated protein kinase kinase (MEK) inhibitor, PD98059, inhibited I(Cl,Aden).
      (4) Reverse transcription-polymerase chain reaction experiments and
      immunocytochemistry confirmed mRNA and protein expression for the CB1 receptor in
      NPCE cells, and the CB1 receptor agonist, Win 55,212-2, activated a PDBu
      sensitive Cl(-) current (I(Cl,Win)). (5) Transfection of NPCE cells with the
      human CB1 (hCB1) receptor, increased I(Cl,Win), consistent with increased
      receptor expression, and I(Cl,Win) in hCB1 receptor-transfected cells was
      decreased after application of a CB1 receptor inverse agonist, SR 141716. (6)
      Constitutive activity for CB1 receptors was not significant in NPCE cells as
      transfection with hCB1 receptors did not increase basal Cl(-) current, nor was
      basal current inhibited by SR 141716. (7) I(Cl,Win) was inhibited by PTX
      preincubation, by transfection with ct-betaARK and by the MEK inhibitor, PD98059,
      but unaffected by the PI3K inhibitor, wortmannin. (8) We conclude that both A3
      and CB1 receptors activate a PKC-sensitive Cl(-) current in human NPCE cells via
      a G(i/o)/Gbetagamma signaling pathway, in a manner independent of PI3K but
      involving MAPK.

PMID- 12788808
TI  - A specific taurine recognition site in the rabbit brain is responsible for
      taurine effects on thermoregulation.
AB  - (1) Taurine and GABA are recognized as endogenous cryogens. In a previous study,
      some structural analogues of taurine, namely 6-aminomethyl-3-methyl-4H-1,2,4
      benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2
      hydroxyethanesulfonic (ISE) and (+/-)cis-2-aminocyclohexane sulfonic acids (CAHS)
      have been shown to displace [(3)H]taurine binding from rabbit brain synaptic
      membrane preparations, without interacting either with GABA-ergic systems, nor
      with taurine uptake mechanism, thus behaving like direct taurinergic agents. (2)
      To answer the question whether the role of taurine as an endogenous cryogen
      depends on the activation of GABA receptors or that of specific taurine
      receptor(s), taurine or the above structural analogues were injected
      intracerebroventricularly in conscious, restrained rabbits singularly or in
      combination and their effects on rectal (RT)- and ear-skin temperature and gross
      motor behavior (GMB) were monitored. (3) Taurine (1.2 x 10(-6)-4.8 x 10(-5) mol)
      induced a dose-related hypothermia, vasodilation at ear vascular bed and
      inhibition of GMB. CAHS, at the highest dose tested (4.8 x 10(-5) mol) induced a
      taurine-like effect either on RT or GMB. On the contrary ISE, injected at the
      same doses of taurine, induced a dose-related hyperthermia, vasoconstriction and
      excitation of GMB. AEA and TAG caused a dose-related hyperthermia, but at doses
      higher than 1.2 x 10(-7) mol caused death within 24 h after treatment. (4) CAHS
      (4.8 x 10(-5) mol) antagonized the hyperthermic effect induced by TAG (1.2 x 10(
      6) mol), AEA (1.2 x 10(-8) mol) or ISE (4.8 x 10(-5) mol). (5) In conclusion,
      these findings may indicate the existence of a recognition site specific for
      taurine, responsible for its effects on thermoregulation.

PMID- 12788809
TI  - Bisphenol A diglycidyl ether-induced apoptosis involves Bax/Bid-dependent
      mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and
      Smac/DIABLO.
AB  - (1) Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) antagonist, which is able to induce apoptosis in
      tumor cells independently of PPAR-gamma in caspase-dependent and -independent
      manners. Additionally, BADGE promotes TRAIL-induced apoptosis. (2) We report that
      BADGE activates via Bax and caspases-2 and -8 both the intrinsic and extrinsic
      apoptotic pathways using Bid as a shunt. (3) BADGE stimulates the mitochondrial
      release of apoptosis-inducing factor (AIF), cytochrome c and second mitochondria
      derived activator of caspase/direct IAP-binding protein with low pl
      (Smac/DIABLO). The release of cytochrome c could not be blocked by inhibitors of
      caspases-3, -8 and -9 indicating that BADGE acts upstream of caspases-3 and -9
      and does not involve caspase-8 to release cytochrome c. (4) While the caspase
      independent apoptotic effect might be mediated by AIF, the sensitizing effect of
      BADGE against other apoptotic substances is most likely mediated by the X-linked
      inhibitor of apoptosis inhibitor Smac/DIABLO. (5) Our data suggest that BADGE or
      BADGE derivatives could represent promising substances for the treatment of
      neoplasms improving the antitumoral activity of TRAIL.

PMID- 12788810
TI  - Control of signalling efficacy by palmitoylation of the rat Y1 receptor.
AB  - (1) We have investigated the properties of native and haemagglutinin (HA)-tagged
      neuropeptide Y (NPY) Y(1) receptors after mutation of the palmitoylation site
      Cys(337) to Ser or Ala. (2) In Chinese hamster ovary cells expressing similar
      receptor levels, the C337A mutation abolished incorporation of [(3)H]palmitic
      acid into the HA-Y(1) receptor. (3) Cys(337) substitution did not alter the
      affinities of Y(1) receptor agonists or antagonists, but it eliminated the
      ability of guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) to displace
      [(125)I]PYY-specific binding (compared to approximately 50% inhibition in Y(1) or
      HA-Y(1) clones). (4) Stimulation of GTPgamma[(35)S] binding by native and HA-Y(1)
      receptors in standard incubation buffer (100 mM NaCl, 10 micro M GDP) was
      prevented by Cys(337) mutation. In this assay, the function of Y(1)(C337S)
      receptors could be partially rescued by reducing the Na(+) concentration, and
      when overexpressed (B(max): approximately 10 pmol mg(-1)), both HA-Y(1) and HA
      Y(1)(C337A) receptors displayed similar responses to NPY and peptide YY (PYY).
      (5) In stably transfected adenocarcinoma cells expressing Y(1) or Y(1)(C337S)
      receptors, PYY inhibited anion secretion stimulated by vasoactive intestinal
      peptide (VIP; measured as short-circuit current, I(SC)) with similar potency
      (EC(50): 26-53 nM). In contrast to the transient Y(1) receptor-mediated responses
      observed at maximal PYY concentrations, I(SC) reductions in both Y(1)(C337S)
      clones were sustained. (6) We conclude that nonpalmitoylation of the Y(1)
      receptor reduces its coupling efficiency to G proteins, and may also indirectly
      influence desensitisation processes that depend on the formation of an active
      agonist-receptor conformation.

PMID- 12788811
TI  - Effect of sildenafil on cyclic nucleotide phosphodiesterase activity, vascular
      tone and calcium signaling in rat pulmonary artery.
AB  - (1) Sildenafil (viagra) is a potent PDE5 inhibitor and thus a relaxant drug in
      corpus carvernosum smooth muscle. In the present work, we evidenced the presence
      of PDE5 isozyme and investigated the effect of sildenafil on the specific cyclic
      nucleotide phosphodiesterase (PDE) activity, smooth muscle tone and calcium
      signaling in the rat main pulmonary artery (MPA). (2) The PDE activity was
      measured in cytosolic and microsomal fractions. Total cAMP and cGMP-PDE
      activities were mainly present in the cytosolic fraction. Sildenafil (0.1 micro
      M) reduced by 72% cGMP-PDE activity, whereas zaprinast (10 micro M), a relatively
      selective PDE5 inhibitor, reduced this activity by 63%. Sildenafil (0.1 micro M)
      also inhibited significantly (22%) the cAMP-PDE activity. (3) Western blot
      analysis revealed the expression of PDE5 mainly in the cytosolic fraction of MPA.
      Sildenafil concentration-dependently inhibited (IC(50)=3.4 nM) the activity of
      MPA PDE5 partially purified by HPLC. (4) Sildenafil (0.1 nM-50 micro M)
      concentration-dependently relaxed MPA rings precontracted with phenylephrine (0.5
      micro M). The potency of sildenafil (IC(50)=11 nM) was similar to that of a
      nitric oxide donor, sodium nitroprusside, but higher than that of zaprinast
      (IC(50)=600 nM). The vasorelaxant effect of sildenafil was not altered by
      endothelium removal or in the presence of KT 5823 (1 micro M) and H89 (1 micro
      M), potent inhibitors of PKG and PKA, respectively. (5) In isolated MPA myocytes,
      which had been loaded with the calcium fluorophore indo-1, sildenafil (10-100 nM)
      antagonized ATP- and endothelin-1-induced calcium oscillations but had no effect
      on the transient caffeine-induced [Ca(2+)](i) response. (6) This study
      demonstrates the presence of a functional and highly sildenafil-sensitive PDE5
      isozyme in rat MPA. Inhibition of this isozyme mainly accounts for the potent
      pulmonary vasodilator action of sildenafil, which involves alteration in the
      inositol triphosphate-mediated calcium signaling pathway.

PMID- 12788813
TI  - Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and
      Kv1.4 K+ channels expressed in HEK293 cells.
AB  - (1) We have determined the molecular basis of nicardipine-induced block of
      cardiac transient outward K(+) currents (I(to)). Inhibition of I(to) was studied
      using cloned voltage-dependent K(+) channels (Kv) channels, rat Kv4.3L, Kv4.2,
      and Kv1.4, expressed in human embryonic kidney cell line 293 (HEK293) cells. (2)
      Application of the dihydropyridine Ca(2+) channel antagonist, nicardipine,
      accelerated the inactivation rate and reduced the peak amplitude of Kv4.3L
      currents in a concentration-dependent manner (IC(50): 0.42 micro M). The
      dihydropyridine (DHP) Ca(2+) channel agonist, Bay K 8644, also blocked this K(+)
      current (IC(50): 1.74 micro M). (3) Nicardipine (1 micro M) slightly, but
      significantly, shifted the voltage dependence of activation and steady-state
      inactivation to more negative potentials, and also slowed markedly the recovery
      from inactivation of Kv4.3L currents. (4) Coexpression of K(+) channel
      interacting protein 2 (KChIP2) significantly slowed the inactivation of Kv4.3L
      currents as expected. However, the features of DHP-induced block of K(+) current
      were not substantially altered. (5) Nicardipine exhibited similar block of Kv1.4
      and Kv4.2 channels stably expressed in HEK293 cells; IC(50)'s were 0.80 and 0.62
      micro M, respectively. (6) Thus, at submicromolar concentrations, DHP Ca(2+)
      antagonist and agonist inhibit Kv4.3L and have similar inhibiting effects on
      other components of cardiac I(to), Kv4.2 and Kv1.4.

PMID- 12788812
TI  - Tachykinins and tachykinin receptors in human uterus.
AB  - (1) Studies were undertaken to determine the nature of the receptors mediating
      contractile effects of tachykinins in the uteri of nonpregnant women, and to
      analyse the expression of preprotachykinins (PPT), tachykinin receptors and the
      cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and
      nonpregnant women. (2) The neurokinin B (NKB) precursor PPT-B was expressed in
      higher levels in the myometrium from nonpregnant than from pregnant women. Faint
      expression of PPT-A mRNA was detectable in the myometrium from nonpregnant but
      not pregnant women. PPT-C, the gene encoding the novel tachykinin peptide
      hemokinin-1 (HK-1), was present in trace amounts in the uteri from both pregnant
      and nonpregnant women. (3) Tachykinin NK(2) receptors were more strongly
      expressed in tissues from nonpregnant than from pregnant women. NK(1) receptor
      mRNA was present in low levels in tissues from both pregnant and nonpregnant
      women. A low abundance transcript corresponding to the NK(3) receptor was present
      only in tissues from nonpregnant women. (4) The mRNA expression of the tachykinin
      degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant
      women. (5) Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the
      peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of
      myometrium from nonpregnant women. The order of potency was NKA>>SP>/=NKB. The
      potency of NKA was unchanged in the absence of peptidase inhibitors. (6) The
      tachykinin NK(2) receptor-selective agonist [Lys(5)MeLeu(9)Nle(10)]NKA(4-l0) was
      approximately equipotent with NKA, but the tachykinin NK(1) and NK(3) receptor
      selective agonists [Sar(9)Met(O(2))(11)]SP and [MePhe(7)]NKB were ineffective in
      the myometrium from nonpregnant women. (7) The uterotonic effects of
      [Lys(5)MeLeu(9)Nle(10)]NKA(4-10) were antagonized by the tachykinin NK(2)
      receptor-selective antagonist SR48968. Neither atropine, nor phentolamine nor
      tetrodotoxin affected responses to [Lys(5)MeLeu(9)Nle(10)]NKA(4-10). (8) These
      data are consistent with a role of tachykinins in the regulation of human uterine
      function, and reinforce the importance of NK(2) receptors in the regulation of
      myometrial contraction.

PMID- 12788815
TI  - Molecular cloning and characterization of avian bombesin-like peptide receptors:
      new tools for investigating molecular basis for ligand selectivity.
AB  - (1) Bombesin (BN), originally isolated from amphibians, is structurally related
      to a family of BN-like peptides found in mammals, which include gastrin-releasing
      peptide (GRP) and neuromedin B (NMB). These peptides have important effects on
      secretion, smooth muscle contraction, metabolism and behavior. Here we report
      cloning and characterization of two subtypes of BN-like peptide receptors in
      Aves. (2) The amino-acid sequence of chick GRP-R (chGRP-R) is highly identical
      with mammalian and amphibian GRP-R, and this receptor showed high affinity for
      GRP, BN and synthetic bombesin agonist, [D-Phe(6), beta-Ala(11), Phe(13),
      Nle(14)]bombesin(6-14) ([FAFNl]BN(6-14)). The chGRP-R gene was localized to
      chicken chromosome 1q23distal-q24proximal, where chick homologs of other human X
      linked genes have also been mapped. (3) ChBRS-3.5, having sequence similarities
      to both mammalian bombesin-like peptide receptor subtype-3 and amphibian bombesin
      like peptide receptor subtype-4, showed high affinity for [FAFNl]BN(6-14),
      moderate affinity for BN, but low affinity for both GRP and NMB. (4) Expression
      of both receptors was detected in brain, but only chGRP-R was expressed in
      gastrointestinal (GI) tissues. (5) When expressed in Chinese hamster ovary K1
      cells, these receptors mediate intracellular calcium mobilization upon agonist
      stimulation. These results suggest that a novel BN peptide may occur in Aves as
      an endogenous ligand for chBRS-3.5. (6) The receptor sequences responsible for
      ligand selectivities were discussed and this knowledge about avian BN-like
      peptide receptors will help us to understand the molecular basis for agonist
      sensitivities of BN-like peptide receptors.

PMID- 12788814
TI  - Protein kinase C-alpha attenuates cholinergically stimulated gastric acid
      secretion of rabbit parietal cells.
AB  - (1) The phorbolester 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of
      protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid
      secretion. We observed that this effect strongly correlated with the inhibition
      of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity in rabbit
      parietal cells. (2) The aim of this study was to specify the function of PKC
      alpha in cholinergically stimulated H(+) secretion. PKC-alpha represents the only
      calcium-dependent PKC isoenzyme that has been detected in rabbit parietal cells.
      (3) Go 6976, an inhibitor of calcium-dependent PKC, concentration-dependently
      antagonized the inhibitory effect of TPA, and, therefore, revealed the action of
      PKC-alpha on carbachol-induced acid secretion in rabbit parietal cells. (4) TPA
      exerted no additive inhibition of carbachol-stimulated acid secretion if acid
      secretion was partially inhibited by the potent CaMKII inhibitor 1-[N,O-bis(5
      isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-piperazine (KN-62). (5) Since
      both kinase modulators, TPA and KN-62, affected no divergent signal transduction
      pathways in the parietal cell, an in vitro model has been used to study if PKC
      directly targets CaMKII. CaMKII purified from parietal cell-containing gastric
      mucosa of pig, was transphosphorylated by purified cPKC containing PKC-alpha up
      to 1.8 mol P(i) per mol CaMKII in vitro. The autonomy site of CaMKII was not
      transphosphorylated by PKC. (6) The phosphotransferase activity of the purified
      CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was
      absent during transphosphorylation. Attenuation of CaMKII activity by PKC showed
      strong similarity to the downregulation of CaMKII by basal autophosphorylation.
      (7) Our results suggest that PKC-alpha and CaMKII are closely functionally linked
      in a cholinergically induced signalling pathway in rabbit parietal cells. We
      assume that in cholinergically stimulated parietal cells PKC-alpha transinhibits
      CaMKII activity, resulting in an attenuation of acid secretion.

PMID- 12788816
TI  - The antipsychotic drug chlorpromazine inhibits HERG potassium channels.
AB  - (1) Acquired long QT syndrome (aLQTS) is caused by prolongation of the cardiac
      action potential because of blockade of cardiac ion channels and delayed
      repolarization of the heart. Patients with aLQTS carry an increased risk for
      torsade de pointes arrhythmias and sudden cardiac death. Several antipsychotic
      drugs may cause aLQTS. Recently, cases of QTc prolongation and torsade de pointes
      associated with chlorpromazine treatment have been reported. Blockade of human
      ether-a-go-go-related gene (HERG) potassium channels, which plays a central role
      in arrhythmogenesis, has previously been reported to occur with chlorpromazine,
      but information on the mechanism of block is currently not available. We
      investigated the effects of chlorpromazine on cloned HERG potassium channels to
      determine the biophysical mechanism of block. (2) HERG channels were
      heterologously expressed in Xenopus laevis oocytes, and ion currents were
      measured using the two-microelectrode voltage-clamp technique. (3) Chlorpromazine
      blocked HERG potassium channels with an IC(50) value of 21.6 micro M and a Hill
      coefficient of 1.11. (4) Analysis of the voltage dependence of block revealed a
      reduction of inhibition at positive membrane potentials. (5) Inhibition of HERG
      channels by chlorpromazine displayed reverse frequency dependence, that is, the
      amount of block was lower at higher stimulation rates. No marked changes in
      electrophysiological parameters such as voltage dependence of activation or
      inactivation, or changes of the inactivation time constant were observed. (6) In
      conclusion, HERG channels were blocked in the closed and activated states, and
      unblocking occurred very slowly.

PMID- 12788817
TI  - Growth hormone secretagogues modulate the electrical and contractile properties
      of rat skeletal muscle through a ghrelin-specific receptor.
AB  - (1) Growth hormone secretagogues (GHS) exhibit potent growth hormone (GH)
      releasing activity through the activation of a pituitary receptor. Here, we
      consider the possibility that GHS can target a specific receptor in rat skeletal
      muscle and have a role in the control of muscle function. (2) By means of the
      intracellular microelectrode technique, we found that in vitro application of
      hexarelin and L-163,255 dose dependently reduced resting chloride (gCl) and
      potassium (gK) conductances in rat skeletal muscle. These effects were prevented
      by the GHS-receptor antagonist [D-Lys-3]-GHRP-6, and by either phospholipase C or
      protein kinase C (PKC) inhibitors. Ghrelin, a natural ligand of GHS receptors,
      also induced a reduction of muscle gCl and gK, which was antagonised by [D-Lys-3]
      GHRP-6. (3) Both GHS shifted the mechanical threshold for the contraction of
      muscle fibres towards more negative voltages. Accordingly, by means of FURA-2
      fluorescent measurements, we demonstrated that L-163,255 induced a resting
      [Ca(2+)](i) increase, which was reversible and not blocked by nifedipine or
      removal of external Ca(2+). (4) Ageing is a condition characterised by a deficit
      of GH secretion, which in turn modifies the electrical and contractile properties
      of skeletal muscle. In contrast to GH, chronic treatment of aged rats with
      hexarelin or L-163,255 failed to restore the electrical and contractile muscle
      properties. Moreover, the two GHS applied in vitro were able to antagonise the
      beneficial effect on gCl and gK obtained through chronic treatment of aged
      animals with GH. (5) Thus, skeletal muscle expresses a specific GHS receptor able
      to decrease gCl and gK through a PKC-mediated intracellular pathway. This
      peripheral action may account for the lack of restoration of skeletal muscle
      function in long-term GHS-treated aged animals.

PMID- 12788818
TI  - Endothelium-independent relaxation to cannabinoids in rat-isolated mesenteric
      artery and role of Ca2+ influx.
AB  - (1) Three cannabinoid receptor agonists, anandamide (CB(1) receptor-selective)
      and the aminoalkyl-indoles, JWH 015(2-methyl-1-propyl-1H-indol-3-yl)-1
      napthalenylmethanone; (CB(2) receptor-selective), R-(+)-WIN 55,212-2 (R-(+)-[2,3
      dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolol[1,2,3-de]-1,4-benzoxazin-6-yl]-1
      napthalenylmethanone; slightly CB(2) receptor-selective), as well as the
      enantiomer S-(-)-WIN 55,212-3(S-(-)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolol[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone;
      inactive at cannabinoid receptors), induced endothelium-independent relaxation of
      methoxamine-precontracted isolated small mesenteric artery of rat. KCL (60 mM)
      precontraction did not affect relaxation to the aminoalkylindoles, but reduced
      that to anandamide. (2) SR14176A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3 micro M; CB(1) receptor
      antagonist) inhibited relaxation only to JWH 015 and anandamide. Neither AM 251
      (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide; CB(1) antagonist) nor SR 144528 (N-[(1S)-endo-1,3,3-trimethyl
      bicyclo[2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)
      pyrazole-3-carboxamide; CB(2) antagonist; both at 3 micro M) affected any of the
      relaxations. (3) Vanilloid receptor desensitisation with capsaicin reduced
      anandamide relaxation; addition of SR 141716A (3 micro M) then caused further
      inhibition. SR 141716A did not affect capsaicin-induced relaxation. (4) The
      aminoalkylindoles inhibited CaCl(2)-induced contractions in methoxamine
      stimulated vessels previously depleted of intracellular Ca(2+). These inhibitory
      effects were greatly reduced or abolished in ionomycin-(a calcium ionophore)
      contracted vessels. Anandamide also caused vanilloid receptor-independent, SR
      141716A- (3 micro M) insensitive, inhibition of CaCl(2) contractions. (5) In
      conclusion, the aminoalkylindoles JWH 015, R-(+)-WIN 55,212-2 and S-(-)-WIN
      55,212-3 relax rat small mesenteric artery mainly by inhibiting Ca(2+) influx
      into vascular smooth muscle. Anandamide causes vasorelaxation by activating
      vanilloid receptors, but may also inhibit Ca(2+) entry. Relaxation to JWH 015 and
      anandamide was sensitive to SR 141716A, but there is no other evidence for the
      involvement of CB(1) or CB(2) receptors in responses to these compounds.

PMID- 12788819
TI  - Involvement of nitric oxide and tachykinins in the effects induced by protease
      activated receptors in rat colon longitudinal muscle.
AB  - (1) The aim of the present study was to verify a possible involvement of nitric
      oxide (NO) and of tachykinins in the contractile and relaxant effects caused by
      the activation of protease-activated receptor (PAR)-1 and PAR-2 in the
      longitudinal muscle of rat colon. (2) Mechanical responses to the PAR-1
      activating peptides, SFLLRN-NH(2) (10 nM-10 micro M) and TFLLR-NH(2) (10 nM-10
      micro M), and to the PAR-2-activating peptide, SLIGRL-NH(2) (10 nM-10 micro M),
      were examined in vitro in the absence and in the presence of different
      antagonists. (3) The relaxation induced by SFLLRN-NH(2), TFLLR-NH(2) and SLIGRL
      NH(2) was antagonised by the inhibitor of NO synthase L-N(omega)-nitroarginine
      methyl ester (300 micro M), or by the inhibitor of the guanylyl cyclase, 1-H
      oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one (10 micro M). (4) The contractile
      responses to PAR-1 and PAR-2 activation were concentration-dependently attenuated
      by SR140333 (0.1-1 micro M), NK(1) receptor antagonist, or by SR48968 (0.1-1
      micro M), NK(2) receptor antagonist. The combined pretreatment with SR140333 (1
      micro M) and SR48968 (1 micro M) produced additive suppressive effects on the
      contractile responses to PAR activation. Pretreatment of the preparation with
      capsaicin (10 micro M) markedly reduced the contractions evoked by SFLLRN-NH(2),
      TFLLR-NH(2) and SLIGRL-NH(2), while omega-conotoxin GVIA (0.2 micro M) had no
      effect. (5) The present results suggest that in rat colonic longitudinal muscle,
      PAR-1 and PAR-2 activation can evoke (i) relaxation through the production of NO
      or (ii) contraction through the release of tachykinins, likely, from sensory
      nerves. These actions may contribute to motility disturbances during intestinal
      trauma and inflammation.

PMID- 12788820
TI  - Effects of G-protein-specific antibodies and G beta gamma subunits on the
      muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle
      cells.
AB  - (1) The effects on the whole-cell carbachol-induced muscarinic cationic current
      (mIcat) of antibodies against the alpha-subunits of various G proteins, as well
      as the effect of a Gbetagamma subunit, were studied in single guinea-pig ileal
      smooth muscle cells voltage-clamped at -50 mV. Ionized intracellular calcium
      concentration, [Ca(2+)](i), was clamped at 100 nM using a 1,2-bis(2-aminophenoxyl
      ethane-N,N,N',N'-tetraacetic acid)/Ca(2+) mixture. (2) Application of ascending
      concentrations of carbachol (1-300 micro M) activated mIcat (mean amplitude 0.83
      nA at 300 micro M carbachol; EC(50) 8 micro M; Hill slope 1.0). A 20 min or
      longer intracellular application via the pipette solution of G(i3)/G(o) or G(o)
      antibodies resulted in about a 70% depression of the maximum response without
      change in the EC(50) value. In contrast, antibodies against alpha-subunits of
      G(i1), G(i1)/G(i2), G(i3), G(q)/G(11) or G(s) protein over a similar or longer
      period did not significantly reduce mIcat. Antibodies to common Gbeta or infusion
      of the Gbetagamma subunit itself had no effect on mIcat. (3) If cells were
      exposed briefly to carbachol (50 or 100 micro M) at early times (<3 min) after
      infusion of antibodies to Galpha(i3)/Galpha(o) or to Galpha(o) had begun,
      carbachol responses remained unchanged even after 20-60 min; that is, the
      depression of mIcat by these antibodies was prevented. (4) These data show that
      Galpha(o) protein couples the muscarinic receptor to the cationic channel in
      guinea-pig ileal longitudinal smooth muscle and that Gbetagamma is not involved.
      They also show that prior activation of the muscarinic receptor presumably causes
      a long-lasting postactivation change of the G protein, which is not reflected in
      mIcat, but acts to hinder antibody binding.

PMID- 12788821
TI  - Development of agonists of endothelin-1 exhibiting selectivity towards ETA
      receptors.
AB  - (1) Endothelin-1 (ET-1) is a bicyclic 21-amino-acid peptide causing a potent and
      sustained vasoconstriction, mainly through the ET(A) receptor subtype. So far, no
      selective ET(A) agonists are described in the literature. (2) A series of
      truncated and chemically modified ET-1 analogues were obtained through solid
      phase peptide synthesis and their biological activity was assessed on rat
      thoracic aorta rings (ET(A) receptors) and guinea-pig lung parenchyma strips
      (ET(B) receptors). (3) Structure-activity studies led to the identification of ET
      1 fragments exhibiting an ET(A) selective agonistic activity. (4) In particular,
      [D-Lys(9)]cyclo(11-15) ET-1(9-21) was the most potent peptide. It appeared as a
      full agonist of ET(A) receptors, being under two orders of magnitude less potent
      than ET-1 (EC(50): 2.3 x 10(-7) vs 6.8 x 10(-9) M). Interestingly, even a linear
      formylated analogue, [Ala(11,15), Trp(For)(21)]ET-1(9-21), showed a selective
      ET(A) activity (EC(50): 3.0 x 10(-6) M). None of the numerous analogues of the
      series exhibited substantial effects in the guinea-pig lung parenchyma bioassay.
      (5) Thus, this study describes the first compounds showing a significant
      bioactivity in an ET(A) pharmacological preparation while being inactive in an
      ET(B) paradigm. They show that the ET-1 pharmacophores, responsible for the ET(A)
      mediated actions, are located within the 9-21 segment of the molecule. Moreover,
      the bicyclic structure of ET-1 does not appear as essential for the ET(A)-related
      vasoconstriction. Results also suggest that the positive charge of the Lys(9)
      side chain participates in an intramolecular ionic bond with the carboxylate
      function of Asp(18).

PMID- 12788822
TI  - Homo- and heteroexchange of adenine nucleotides and nucleosides in rat
      hippocampal slices by the nucleoside transport system.
AB  - (1) Here, we investigated how nucleotides and nucleosides affect the release of
      tritiated purines and endogenous adenosine 5'-triphosphate (ATP) from superfused
      rat hippocampal slices. (2) ATP elicited concentration-dependent [(3)H]purine
      efflux from slices preloaded with [(3)H]adenosine. High-performance liquid
      chromatography analysis of the effluent showed that the tritium label represented
      the whole set of adenine nucleotides and nucleosides, and ATP significantly
      increased the outflow of [(3)H]ATP. (3) Adenosine 5'-diphosphate, adenosine,
      uridine, uridine 5'-triphosphate, alpha,beta-methylene-ATP and 3'-O-(4
      benzoylbenzoyl)-ATP were also active in eliciting [(3)H]purine release. Adenosine
      (300 micro M) also evoked endogenous ATP efflux from the hippocampal slices. (4)
      Reverse transcription-coupled-polymerase chain reaction analysis revealed that
      mRNAs encoding a variety of P2X and P2Y receptor proteins are expressed in the
      rat hippocampus. Nevertheless, neither P2 receptor (i.e. pyridoxal-5-phosphate-6
      azophenyl-2',4'-disulphonic acid, 30 micro M, suramin, 300 micro M and reactive
      blue 2, 10 micro M), nor adenosine receptor (8-cyclopentyl-1,3-dipropylxanthine,
      250 nM and dimethyl-1-propargylxanthine, 250 nM) antagonists modified the effect
      of ATP (300 micro M) to evoke [(3)H]purine release. (5) The nucleoside transport
      inhibitors, dipyridamole (10 micro M), nitrobenzylthioinosine (10 micro M) and
      adenosine deaminase (2-10 U ml(-1)), but not the ecto-adenylate kinase inhibitor
      diadenosine pentaphosphate (200 micro M) significantly reduced ATP-evoked
      [(3)H]purine efflux. (6) In summary, we found that ATP and other nucleotides and
      nucleosides promote the release of one another and themselves by the nucleoside
      transport system. This action could have relevance during physiological and
      pathological elevation of extracellular purine levels high enough to reverse the
      nucleoside transporter.

PMID- 12788823
TI  - Vascular endothelial growth factor increases heme oxygenase-1 protein expression
      in the chick embryo chorioallantoic membrane.
AB  - (1) Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. It
      has been recently suggested that the inducible heme oxygenase (HO-1) isoform may
      play a role in angiogenesis. (2) The aims of this study were to determine, in
      chicken embryo chorioallantoic membranes (CAM), whether VEGF increases HO-1
      protein expression, and, if so, by which molecular mechanism, and whether HO-1
      activity is required for VEGF-induced angiogenesis. (3) Treatment of CAMs with
      VEGF for 48 h caused a significant increase in HO-1 protein expression,
      simultaneously with angiogenesis. (4) VEGF-stimulated angiogenesis in CAMs was
      markedly attenuated by the HO inhibitor zinc mesoporphyrin (ZnMP). This
      inhibitory effect of ZnMP was not observed with copper mesoporphyrin (CuMP), a
      metalloporphyrin that has a similar structure to ZnMP but does not inhibit HO
      enzymatic activity. (5) Overexpression of HO-1 protein elicited by VEGF in CAMs
      was significantly attenuated by the intracellular calcium chelator 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM).
      The effects of BAPTA-AM were, in turn, compensated by the calcium ionophore A
      23187. (6) In addition, the protein kinase C inhibitor staurosporine
      significantly attenuated, in a dose-dependent manner, the VEGF-stimulated HO-1
      induction observed in CAMs. (7) These results demonstrate, for the first time,
      that VEGF upregulates HO-1 protein expression in vivo in CAMs by a mechanism
      dependent on an increase in cytosolic calcium levels and activation of protein
      kinase C. Our findings also suggest that HO-1 activity is necessary for VEGF
      induced angiogenesis in CAMs.

PMID- 12788824
TI  - Chronic cardiotoxicity of anticancer anthracyclines in the rat: role of secondary
      metabolites and reduced toxicity by a novel anthracycline with impaired
      metabolite formation and reactivity.
AB  - (1) The anticancer anthracycline doxorubicin (DOX) causes cardiomyopathy upon
      chronic administration. There is controversy about whether DOX acts directly or
      after conversion to its secondary alcohol metabolite DOXol. Here, the role of
      secondary alcohol metabolites was evaluated by treating rats with cumulative
      doses of DOX or analogues--like epirubicin (EPI) and the novel disaccharide
      anthracycline MEN 10755--which were previously shown to form less alcohol
      metabolites than DOX when assessed in vitro. (2) DOX induced electrocardiographic
      and haemodynamic alterations, like elongation of QalphaT or SalphaT intervals and
      suppression of isoprenaline-induced dP/dt increases, which developed in a time
      dependent manner and were accompanied by cardiomegaly, histologic lesions and
      mortality. EPI caused less progressive or severe effects, whereas MEN 10755
      caused essentially no effect. (3) DOX and EPI exhibited comparable levels of
      cardiac uptake, but EPI formed approximately 60% lower amounts of its alcohol
      metabolite EPIol at 4 and 13 weeks after treatment suspension (P<0.001 vs DOX).
      MEN 10755 exhibited the lowest levels of cardiac uptake; hence, it converted to
      its alcohol metabolite MEN 10755ol approximately 40% less efficiently than did
      EPI to EPIol at either 4 or 13 weeks. Cardiotoxicity did not correlate with
      myocardial levels of DOX or EPI or MEN 10755, but correlated with those of DOXol
      or EPIol or MEN 10755ol (P=0.008, 0.029 and 0.017, respectively). (4) DOX and EPI
      inactivated cytoplasmic aconitase, an enzyme containing an Fe-S cluster liable to
      disassembly induced by anthracycline secondary alcohol metabolites. DOX caused
      greater inactivation of aconitase than EPI, a finding consistent with the higher
      formation of DOXol vs EPIol. MEN 10755 did not inactivate aconitase, which was
      because of both reduced formation and impaired reactivity of MEN 10755ol toward
      the Fe-S cluster. Aconitase inactivation correlated (P<0.01) with the different
      levels of cardiotoxicity induced by DOX or EPI or MEN 10755. (5) These results
      show that (i) secondary alcohol metabolites are important determinants of
      anthracycline-induced cardiotoxicity, and (ii) MEN 10755 is less cardiotoxic than
      DOX or EPI, a behaviour attributable to impaired formation and reactivity of its
      alcohol metabolite.

PMID- 12788825
TI  - Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the
      activity of pig urethral ATP-sensitive K+ channels.
AB  - (1) We have investigated the possible roles of sulphonylurea receptor (SUR) type
      1 and 2B in the activity of pig urethral ATP-sensitive K(+) channels (K(ATP)
      channels) by use of patch-clamp and reverse transcriptase-polymerase chain
      reaction (RT-PCR) techniques. (2) In voltage-clamp experiments, not only
      diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2
      activator, caused an inward current at a holding potential of -50 mV in
      symmetrical 140 mM K(+) conditions. (3) Gliclazide (</=1 micro M), a selective
      SUR1 blocker, inhibited the 10 micro M pinacidil-induced currents (K(i)=177 micro
      M) and the 500 micro M diazoxide-induced currents (high-affinity site, K(i1)=5
      nM; low-affinity site, K(i2)=108 micro M) at -50 mV. (4) Application of
      tolbutamide (</=100 micro M) reversibly caused an inhibition of the 500 micro M
      diazoxide-induced current at -50 mV. (5) MCC-134, a SUR type-specific K(ATP)
      channel regulator (1-100 micro M), produced a concentration-dependent inward K(+)
      current, which was suppressed by the application of glibenclamide at -50 mV. The
      amplitude of the MCC-134 (100 micro M)-induced current was approximately 50% of
      that of the 100 micro M pinacidil-induced currents. (6) Using cell-attached
      configuration, MCC-134 activated a glibenclamide-sensitive K(ATP) channel which
      was also activated by pinacidil. (7) RT-PCR analysis demonstrated the presence of
      SUR1 and SUR2B transcripts in pig urethra. 8 These results indicate that both
      SUR1 and SUR2B subunits play a functional role in regulating the activity of pig
      urethral K(ATP) channels and that SUR1 contributes less than 25% to total K(ATP)
      currents.

PMID- 12788826
TI  - Endothelium-dependent relaxation and endothelial hyperpolarization by P2Y
      receptor agonists in rat-isolated mesenteric artery.
AB  - (1) Vasorelaxation and hyperpolarization of endothelial cells by adenosine 5'
      [beta-thio]diphosphate (ADPbetaS) and adenosine 5'-[gamma-thio]triphosphate
      (ATPgammaS) were studied in rat-isolated mesenteric artery. Effects from
      stimulation of P2X receptors were avoided by desensitization with alpha,beta
      methylene adenosine triphosphate. (2) ADPbetaS caused concentration- and
      endothelium-dependent relaxations of methoxamine-precontracted small (third
      generation) and main mesenteric artery. These were inhibited by N(omega)-nitro-L
      arginine methyl ester (L-NAME) or a combination of apamin plus charybdotoxin
      (inhibitors of Ca(2+)-activated K(+) channels); L-NAME, apamin and charybdotoxin
      applied together abolished the response. (3) ATPgammaS induced limited relaxation
      (35% of methoxamine-induced tone at 10 micro M) of small mesenteric artery, which
      was sensitive to L-NAME or endothelium denudation. However, it almost completely
      relaxed the main mesenteric artery over an extended concentration range (>6
      orders of magnitude) in an endothelium-dependent manner. This relaxation was
      inhibited by either L-NAME or a combination of apamin with charybdotoxin, and
      abolished by a combination of all the three inhibitors. (4) The P2Y(1) receptor
      antagonist MRS 2179 (2'-deoxy-N(6)-methyladenosine 3',5'-bisphosphate; 0.3-3
      micro M) caused parallel rightward shifts of the concentration/relaxation curve
      to ADPbetaS (pA(2)=7.1). However, MRS 2179 did not inhibit, but potentiated,
      relaxant responses to ATPgammaS. MRS 2179 did not affect the contractile
      responses ATPgammaS in small mesenteric artery; ATPgammaS did not contract the
      main mesenteric artery. (5) ADPbetaS hyperpolarized the endothelium of the main
      mesenteric artery in a concentration-dependent manner. This was unaffected by L
      NAME but antagonized by MRS 2179. ATPgammaS also hyperpolarized the mesenteric
      artery endothelium in a concentration-dependent manner but, when ATPgammaS was
      applied at 10 micro M, its effect was potentiated by MRS 2179 (3 micro M). (6) It
      is concluded that both relaxation and hyperpolarization to ADPbetaS are mediated
      by P2Y(1) receptors and that the endothelial hyperpolarization is related to the
      L-NAME-resistant relaxation. Relaxation to the P2Y(2) agonist ATPgammaS shows
      regional variation along the mesenteric vasculature. The mechanisms for
      potentiation of relaxation and hyperpolarization by ATPgammaS are unknown, but
      may indicate interactions between P2Y receptor subtypes.

PMID- 12788829
TI  - 50th anniversary of aldosterone.

PMID- 12788830
TI  - Aldosterone resurgens--letter from EPHESUS.

PMID- 12788827
TI  - Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult
      sensory neurones in culture: a novel role of prostaglandins.
AB  - (1) Peripheral inflammation causes an increase in the proportion of primary
      afferent neurones that express neurokinin(1) (NK(1)) receptors for substance P
      (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory
      pain. The aim of this study was to identify endogenous mediators that stimulate
      upregulation of NK(1) receptors in dorsal root ganglion (DRG) neurones. Cultured
      DRG neurones from the adult normal rat were exposed for 2 days to media that
      contained specific mediators, namely potassium in high concentration,
      prostaglandin E(2) (PGE(2)), somatostatin (SRIF), and compounds influencing
      second messenger cascades. After fixation neurones were labelled with an NK(1)
      receptor antibody. (2) Repetitive addition of the inflammatory mediator PGE(2) or
      dibutyryl-cyclic adenosine 3',5' monophophate (db-cAMP) to the culture medium
      enhanced the proportion of neurones with NK(1) receptor-like immunoreactivity
      from about 12% up to 40%. PGE(2)-induced upregulation was prevented by
      coadministration of PGE(2) and a protein kinase A inhibitor or SRIF to the
      medium. High potassium concentration, protein kinase C inhibitors and omission of
      nerve growth factor from the medium had no effect. (3) In calcium-imaging
      experiments, bath application of SP evoked increases of the intracellular calcium
      concentration in about 20% of the neurones. This proportion increased to about
      40% after PGE(2)-pretreatment, but the increase was prevented when PGE(2) and
      SRIF were coadministered to the medium. (4) These data show that the expression
      of NK(1) receptor-like immunoreactivity in DRG neurones is regulated by the
      inflammatory mediator PGE(2). This upregulation depends on the intracellular
      adenylyl cyclase-protein kinase A pathway.

PMID- 12788831
TI  - Aldosterone: direct effects on and production by the heart.

PMID- 12788832
TI  - Hypertension and the cortisol-cortisone shuttle.
AB  - 11 beta-Hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) plays a crucial role
      in converting hormonally active cortisol to inactive cortisone, thereby
      conferring specificity on the mineralocorticoid receptor. Mutations in the gene
      encoding 11 beta-HSD2 (HSD11B2) account for an inherited form of hypertension,
      the syndrome of apparent mineralocorticoid excess, in which cortisol induces
      hypertension and hypokalemia. A similar clinical picture to apparent
      mineralocorticoid excess occurs after the ingestion of licorice and
      carbenoxolone, which are competitive inhibitors of 11 beta-HSD2. Reduced 11 beta
      HSD2 activity may explain the increased sodium retention in preeclampsia, renal
      disease, and liver cirrhosis. Substrate saturation of 11 beta-HSD2 occurs in
      Cushing's syndrome and explains the mineralocorticoid excess state that
      characterizes ectopic ACTH syndrome. Polymorphic variability in the HSD11B2 gene
      in part determines salt sensitivity, a forerunner for adult onset hypertension.
      Furthermore, reduced placental 11 beta-HSD2 expression might underpin the Barker
      hypothesis, the epidemiological link between reduced birth weight and adult
      hypertension. At a prereceptor level, 11 beta-HSD2 plays a key role in normal
      physiology in the corticosteroid regulation of sodium homeostasis and
      pathophysiology of hypertension.

PMID- 12788833
TI  - Insulin resistance and its potential role in pregnancy-induced hypertension.
AB  - New-onset hypertension (which includes preeclampsia and gestational hypertension)
      is a common and morbid complication of pregnancy. Many features of the insulin
      resistance syndrome have been associated with this condition. These include
      hypertension, hyperinsulinemia, glucose intolerance, obesity, and lipid
      abnormalities. Other accompanying abnormalities may include elevated levels of
      leptin, TNFalpha, tissue plasminogen activator, plasminogen activator inhibitor
      1, and testosterone. The documentation of these features before the onset of
      hypertension in pregnancy suggests that insulin resistance or associated
      abnormalities may have a role in this disorder. Furthermore, the recognition that
      features of the insulin resistance syndrome persist many years after pregnancy
      among women with this condition raises the possibility that these women may have
      increased risk for future cardiovascular disease. These observations suggest that
      interventions to reduce insulin resistance may reduce the risk of both
      hypertension in pregnancy and later life cardiovascular complications, and
      warrant further study.

PMID- 12788834
TI  - Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and
      cardiovascular disease.

PMID- 12788835
TI  - The emergence of the metabolic syndrome with menopause.
AB  - Women with the metabolic syndrome (central obesity, insulin resistance, and
      dyslipidemia) are known to be at especially high risk for cardiovascular disease
      (CVD). The prevalence of the metabolic syndrome increases with menopause and may
      partially explain the apparent acceleration in CVD after menopause. The
      transition from pre- to postmenopause is associated with the emergence of many
      features of the metabolic syndrome, including 1) increased central
      (intraabdominal) body fat; 2) a shift toward a more atherogenic lipid profile,
      with increased low density lipoprotein and triglycerides levels, reduced high
      density lipoprotein, and small, dense low density lipoprotein particles; 3) and
      increased glucose and insulin levels. The emergence of these risk factors may be
      a direct result of ovarian failure or, alternatively, an indirect result of the
      metabolic consequences of central fat redistribution with estrogen deficiency. It
      is unclear whether the transition to menopause increases CVD risk in all women or
      only those who develop features of the metabolic syndrome. This article will
      review the features of the metabolic syndrome that emerge with estrogen
      deficiency. A better understanding of these metabolic changes with menopause will
      aid in the recognition and treatment of women at risk for future CVD, leading to
      appropriate interventions.

PMID- 12788836
TI  - The metabolic syndrome: peroxisome proliferator-activated receptor gamma and its
      therapeutic modulation.
AB  - By the end of this decade, it has been estimated that between 200 million and 300
      million people worldwide will meet World Health Organization diagnostic criteria
      for diabetes mellitus. This epidemic of predominantly type 2 diabetes has largely
      been mediated by our shift toward a more sedentary lifestyle predisposing to
      obesity and insulin resistance. Affected individuals can also exhibit an array of
      associated undesirable traits such as hypertension, dyslipidemia, and
      hypercoagulability, leading to morbidity and mortality from atherosclerotic
      vascular disease. The coexistence of several of these traits with insulin
      resistance constitutes the metabolic syndrome. Accordingly, improving insulin
      sensitivity in this group, and thereby potentially ameliorating the excess
      vascular risk, is a primary goal of treatment. Recent interest has focused on the
      thiazolidinediones, a novel class of antidiabetic agents, which act as insulin
      sensitizers and, therefore, potentially target the underlying metabolic
      disturbance. These agents are high-affinity ligands for the nuclear receptor
      peroxisome proliferator-activated receptor gamma, and a large body of in vitro
      and in vivo data has evolved to support their increasing clinical use.
      Importantly, clinical and laboratory findings in human subjects harboring natural
      mutations and polymorphisms within the receptor have provided additional
      insights. Here, we focus on the consequences of inherited variation in the human
      peroxisome proliferator-activated receptor gamma gene, linking this receptor to
      disordered glucose homeostasis, adipogenesis, lipid metabolism, and blood
      pressure regulation. These studies provide further support for the future
      development of more selective receptor modulators, targeting specific pathways to
      ameliorate facets of the metabolic syndrome.

PMID- 12788837
TI  - The potential influence of inflammation and insulin resistance on the
      pathogenesis and treatment of atherosclerosis-related complications in type 2
      diabetes.

PMID- 12788838
TI  - The rationale and management of hyperglycemia for in-patients with cardiovascular
      disease: time for change.
AB  - There is increasing evidence that aggressive glycemic control for patients
      admitted into the hospital improves clinical outcomes, especially for patients
      with cardiovascular disease. There appear to be a variety of mechanisms for this.
      Although hyperglycemia has been shown to result in poor wound healing and more
      infectious complications, especially after cardiac surgical procedures, what has
      become clear is that the treatment of hyperglycemia with i.v. glucose, insulin,
      and potassium (GIK) results in better clinical outcomes even in patients without
      diabetes. The mechanisms for this are not year clear, but could be related to the
      insulin administration, perhaps due to suppression of various cytokines or free
      fatty acids. The practical use of insulin in these patients requires basic
      understanding of the use of both i.v. and s.c. insulin. Although there are
      several appropriate options for both of these routes of administration, it is
      critical that all caregivers involved in this population's care are knowledgeable
      about insulin strategies.

PMID- 12788839
TI  - Hypothyroidism and atherosclerosis.

PMID- 12788840
TI  - Medical management of hyperlipidemia/dyslipidemia.

PMID- 12788841
TI  - Pharmacological therapy of obesity: past, present, and future.

PMID- 12788842
TI  - New markers for cardiovascular disease risk in women: impact of endogenous
      estrogen status and exogenous postmenopausal hormone therapy.
AB  - The role of estrogen in altering cardiovascular disease risk in women is
      contentious. Menopause is associated with increased risk for ischemic heart
      disease and cerebrovascular disease, which collectively are the main causes of
      morbidity and mortality in women of developed nations. Observational studies
      suggest a protective role of estrogen, whereas recent randomized controlled
      trials report a negative role for oral estrogen in primary and secondary
      prevention of cardiovascular events. Inflammatory mechanisms underlie the process
      of arterial thrombus formation following atheromatous plaque rupture, and as such
      modulation of the inflammatory process may be a potential means of reducing
      cardiovascular risk. Sex steroids may influence inflammatory processes and hence
      modify cardiovascular risk. The objective of the study was to review the current
      understanding of the relationships between C-reactive protein (CRP),
      homocysteine, IL-6, and lipoprotein (a) [Lp(a)] and endogenous estrogen status,
      exogenous estrogen treatment, and cardiovascular disease risk. The design was a
      review of all relevant published, peer- reviewed studies. Raised levels of CRP,
      homocysteine, Lp(a), IL-6, and CRP are each independently associated with
      increased risk for cardiovascular events in women. Changes in these parameters
      across the menopausal transition cannot clearly be attributed to hormonal
      changes. With respect to the effects of exogenous postmenopausal therapy, oral
      estrogen use is consistently associated with elevations in CRP, no change or a
      reduction in homocysteine, varied effects on IL-6, and a consistent reduction in
      Lp(a). Transdermal estradiol overall has no significant effect on any of these
      parameters. Progestin use appears to attenuate the effect of oral estrogen on CRP
      and is associated with a reduction in Lp(a). Like oral estrogen, tibolone use is
      associated with a rise in CRP, with no change in homocysteine and consistent
      lowering of Lp(a). Selective estrogen receptor modulators modestly lower
      homocysteine and Lp(a), have varied effects on CRP, and have no reported effects
      on IL-6. Despite these varied effects of postmenopausal hormone treatment on
      inflammatory markers, homocysteine, and Lp(a), there is no evidence that change
      in these markers results in modification of cardiovascular risk. Further studies
      are required to specifically investigate whether treatments that increase or
      decrease these markers in fact modulate the risk of cardiovascular events in
      women.

PMID- 12788843
TI  - Adult-onset growth hormone deficiency: Relation of postprandial dyslipidemia to
      premature atherosclerosis.

PMID- 12788844
TI  - Variability in the renin/aldosterone profile under random and standardized
      sampling conditions in primary aldosteronism.
AB  - An increased plasma aldosterone concentration (PAC) with decreased plasma renin
      activity (PRA) is the abnormal endocrine finding in primary aldosteronism (PA).
      However, it remains unknown whether this profile is universal when blood samples
      are obtained in a random manner. We retrospectively evaluated the
      renin/aldosterone profile in 71 patients with PA due to unilateral adrenal
      adenoma. Blood samples were obtained randomly at an out-patient clinic and under
      standardized conditions during hospitalization before surgery. The frequency of
      PAC above 15 ng/dl, PRA below 0.5 ng angiotensin I/ml x h, and a PAC/PRA ratio
      greater than 35 was determined. These three variables showed a large intra- and
      interpatient variation. At least one measurement of PAC, PRA, and PAC/PRA ratio
      was in the normal range in 39%, 48%, and 31% of patients, respectively. Only 37%
      of patients always had the characteristic profile associated with PA. The mean
      values of PAC at the out-patient clinic were slightly, but significantly, lower
      than those in the hospital. These results clearly demonstrated that the
      renin/aldosterone profile in PA is not always abnormal due in part to conditions
      for blood sampling. We conclude that a single normal PAC, PRA, or PAC/PRA ratio
      does not excluded the diagnosis of PA in a hypertensive patient, but repeated
      measurements yields one or more abnormal parameters in the vast majority of
      patients. The PAC/PRA ratio is recommended to use as a screening, but other
      testing is required to arrive at the correct diagnosis.

PMID- 12788845
TI  - A biallelic gene polymorphism of CYP11B2 predicts increased aldosterone to renin
      ratio in selected hypertensive patients.
AB  - Altered control of aldosterone synthase (CYP11B2) gene expression may modulate
      aldosterone secretion, as suggested by a raised aldosterone to renin ratio (ARR)
      in some patients with essential hypertension. We compared the frequency of two
      linked CYP11B2 polymorphisms, one in the steroidogenic factor-1 (SF-1) binding
      site and the other an intronic conversion (Int2) in relation to ARR in 141
      hypertensive patients. Patients were divided into groups with either normal or
      high supine ARR using a cut-off threshold of 145 pmol/liter per ng/liter. Supine
      ARR was normal in 104 patients and raised in 37 patients. The two polymorphisms
      were in strong linkage disequilibrium (chi(2) = 123.8; P < 0.0001). The SF-1 T
      and Int2 C alleles were more prevalent among patients with high ARR (46% and 43%,
      respectively) than with normal ARR (22% and 17%; P < 0.01 and P < 0.005,
      respectively). Odds ratios for raised ARR in subjects with a homozygous SF-1 T
      and Int2 C haplotype were 6.1 (95% confidence interval, 1.6-22.5; P < 0.005) when
      compared with the contrasting haplotype. Linear modeling of individual postural
      changes in renin and aldosterone showed a maximal achievable aldosterone increase
      of 110 pmol/liter with no mutated haplotype and 500 pmol/liter with two mutated
      haplotypes. These findings support the view of a molecular basis regulating
      aldosterone production.

PMID- 12788846
TI  - Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene
      in a case of apparent mineralocorticoid excess.
AB  - The human microsomal 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2)
      metabolizes active cortisol into cortisone and protects the mineralocorticoid
      receptor from glucocorticoid occupancy. In a congenital deficiency of 11 beta
      HSD2, the protective mechanism fails and cortisol gains inappropriate access to
      mineralocorticoid receptor, resulting in low-renin hypertension and hypokalemia.
      In the present study, we describe the clinical and molecular genetic
      characterization of a patient with a new mutation in the HSD11B2 gene. This is a
      4-yr-old male with arterial hypertension. The plasma renin activity and serum
      aldosterone were undetectable in the presence of a high cortisol to cortisone
      ratio. PCR amplification and sequence analysis of HSD11B2 gene showed the
      homozygous mutation in exon 4 Asp223Asn (GAC-->AAC) and a single nucleotide
      substitution C-->T in intron 3. Using site-directed mutagenesis, we generated a
      mutant 11 beta HSD2 cDNA containing the Asp223Asn mutation. Wild-type and mutant
      cDNA was transfected into Chinese hamster ovary cells and enzymatic activities
      were measured using radiolabeled cortisol and thin-layer chromatography. The mRNA
      and 11 beta HSD2 protein were detected by RT-PCR and Western blot, respectively.
      Wild-type and mutant 11 beta HSD2 protein was expressed in Chinese hamster ovary
      cells, but the mutant enzyme had only 6% of wild-type activity. In silico 3D
      modeling showed that Asp223Asn changed the enzyme's surface electrostatic
      potential affecting the cofactor and substrate enzyme-binding capacity. The
      single substitution C-->T in intron 3 (IVS3 + 14 C-->T) have been previously
      reported that alters the normal splicing of pre-mRNA, given a nonfunctional
      protein. These findings may determine the full inactivation of this enzyme,
      explaining the biochemical profile and the early onset of hypertension seen in
      this patient.

PMID- 12788847
TI  - Different inactivating mutations of the mineralocorticoid receptor in fourteen
      families affected by type I pseudohypoaldosteronism.
AB  - We have analyzed the human mineralocorticoid receptor (hMR) gene in 14 families
      with autosomal dominant or sporadic pseudohypoaldosteronism (PHA1), a rare form
      of mineralocorticoid resistance characterized by neonatal renal salt wasting and
      failure to thrive. Six heterozygous mutations were detected. Two frameshift
      mutations in exon 2 (insT1354, del8bp537) and one nonsense mutation in exon 4
      (C2157A, Cys645stop) generate truncated proteins due to premature stop codons.
      Three missense mutations (G633R, Q776R, L979P) differently affect hMR function.
      The DNA binding domain mutant R633 exhibits reduced maximal transactivation,
      although its binding characteristics and ED(50) of transactivation are comparable
      with wild-type hMR. Ligand binding domain mutants R776 and P979 present reduced
      or absent aldosterone binding, respectively, which is associated with reduced or
      absent ligand-dependent transactivation capacity. Finally, P979 possesses a
      transdominant negative effect on wild-type hMR activity, whereas mutations G633R
      and Q776R probably result in haploinsufficiency in PHA1 patients. We conclude
      that hMR mutations are a common feature of autosomal dominant PHA1, being found
      in 70% of our familial cases. Their absence in some families underscores the
      importance of an extensive investigation of the hMR gene and the role of precise
      diagnostic procedures to allow for identification of other genes potentially
      involved in the disease.

PMID- 12788848
TI  - A compound heterozygote case of type II aldosterone synthase deficiency.
AB  - An infant with failure to thrive, persistent hyponatremia and episodic vomiting
      and diarrhea was admitted to hospital at 9 months of age, and the diagnosis of
      type II aldosterone synthase deficiency was confirmed by plasma and urinary
      steroid determinations. The entire coding sequence of the aldosterone synthase
      gene (CYP11B2) was determined (both strands) in the affected infant, an
      unaffected sibling, and both parents. An exon 3 mutation (C554T, leading to amino
      acid T185I) was found in the father and both siblings, and an exon 9 mutation
      (A1492G, leading to T498A) was found in the affected infant and the mother.
      Expression of the mutant sequences in COS cells showed steroidogenic patterns
      typical of aldosterone synthase type II deficiency, including very low levels of
      aldosterone synthesis (< or =0.5% of wild-type enzyme) consistent with the low
      aldosterone levels in the patient's plasma. Both mutations in this compound
      heterozygote localize to the beta 3-sheet in the cytochrome P450 enzyme
      structure, as does the previously characterized R181W mutation. This region of
      the enzyme is not part of the putative structural core, but mutations to this
      region suggest that it is important for conferring the unique ability of
      aldosterone synthase to catalyze efficient oxygenation of the C(18) carbon of
      steroid substrates.

PMID- 12788849
TI  - Cardiovascular risk factors and common carotid artery caliber and stiffness in
      patients with Cushing's disease during active disease and 1 year after disease
      remission.
AB  - Cardiovascular accidents represent the most important cause of death in patients
      with Cushing's syndrome. This prospective study aims at evaluating carotid
      arteries by echo-Doppler ultrasonography and clinical and metabolic markers of
      atherosclerosis in 25 patients with Cushing's disease (CD) before and after 1 yr
      of remission. Thirty-two sex- and age-matched subjects (control-1) and 32 body
      mass index-matched subjects (control-2) served as controls. At diagnosis, CD
      patients had higher body mass index, waist to hip ratio (WHR), total, low-density
      lipoprotein-cholesterol and total/high-density lipoprotein (HDL) ratio, glucose
      and insulin, as well as lower HDL-cholesterol than control-1; they had higher WHR
      and total/HDL ratio and lower HDL-cholesterol than control-2. They also had
      higher intima-media thickness (IMT), and lower systolic lumen diameter and
      distensibility coefficient (DC) than either control group. Atherosclerotic
      plaques were detected in 31.2% of patients, 0 control-1, and 6.2% of control-2
      subjects. One year after remission, WHR, LDL-cholesterol, and IMT significantly
      decreased, whereas systolic lumen diameter and DC significantly increased.
      However, all of the above parameters were still abnormal compared with control-1,
      but not control-2. A significant correlation was found between WHR, glucose and
      insulin levels, and right and left carotid IMT. WHR was the best predictor of
      left IMT and left DC in active, but not in cured, patients. The duration of
      hypercortisolism was the best predictor of right DC in active but not in cured
      patients. In conclusion, patients with CD have severe atherosclerotic damage. The
      persistence of a metabolic syndrome, vascular damage, and atherosclerotic plaques
      after cortisol level normalization makes these subjects still at high
      cardiovascular risk despite disease remission.

PMID- 12788850
TI  - Obesity, regional fat distribution, and syndrome X in obese black versus white
      adolescents: race differential in diabetogenic and atherogenic risk factors.
AB  - The incidence of type 2 diabetes mellitus in children is increasing with the
      increasing prevalence of obesity, particularly in African-American children. We
      hypothesized that African-American obese adolescents are more insulin resistant
      than their white peers, but have lower insulin secretion, thus increasing their
      risk of type 2 diabetes mellitus. The present study investigated insulin
      sensitivity and secretion, visceral adiposity (VAT), and cardiovascular disease
      (CVD) risk profile in black obese adolescents (BOA) vs. white obese adolescents
      (WOA). Twenty-four BOA and 26 WOA underwent a hyperinsulinemic-euglycemic clamp
      to assess insulin sensitivity, a hyperglycemic clamp to determine insulin
      secretion, dual energy x-ray absorptiometry for body composition and computed
      tomography scan at L4-L5 to measure VAT and sc abdominal adipose tissue. Fasting
      lipid and automated blood pressure measurements were obtained. The WOA and BOA
      groups were divided into low VAT and high VAT groups. BOA compared with WOA of
      similar body mass index and percent body fat had less visceral adiposity, lower
      hepatic glucose production, and lower lipid levels. Visceral adiposity was
      associated with lower insulin sensitivity in both groups [low vs. high VAT; BOA,
      2.9 +/- 0.4 vs. 1.7 +/- 0.2 micromol/kg x min per pmol/liter (P = 0.016); WOA,
      2.6 +/- 0.5 vs. 1.5 +/- 0.1 (P = 0.032)]. However, this was compensated by higher
      insulin secretion in whites (low VAT, 934.8 +/- 121.8; high VAT, 1590.6 +/- 232.8
      pmol/liter; P = 0.037), but not in blacks (low VAT, 1398.9 +/- 214.0; high VAT,
      1423.7 +/- 108.7 pmol/liter). Glucose disposition index (insulin sensitivity x
      first phase insulin) was lower in high VAT vs. low VAT BOA, but not in WOA. In
      each racial group, high VAT groups had elevation of systolic and diastolic blood
      pressure, but dyslipidemia was worse in WOA with high VAT. In conclusion, a given
      level of body mass index confers different metabolic risks for WOA vs. BOA.
      Although differences in fat patterning may help explain the more atherogenic risk
      profile in whites, the cause of the more diabetogenic insulin
      sensitivity/secretion profile in blacks remains unknown and needs to be
      investigated further.

PMID- 12788851
TI  - Clinical features and genetic analysis of autosomal recessive
      hypercholesterolemia.
AB  - Previously we have reported on siblings with severe hypercholesterolemia,
      xanthomas, and premature atherosclerosis without any impairment of low-density
      lipoprotein receptor in their fibroblasts as a first characterization of
      autosomal recessive hypercholesterolemia (ARH). Recently, mutations were
      identified for this disease in a gene encoding a putative adaptor protein. The
      purpose of this study was to examine the molecular pathogenesis of ARH in
      Japanese siblings. A novel insertion mutation was discovered in the ARH gene of
      the siblings. An insertion of an extra cytosine residue was identified in a locus
      comprising eight consecutive cytosines at positions 599 through 606 in exon 6,
      resulting in a sequence of nine cytosines and generating an early stop codon at
      657-659. The mother was heterozygous for this mutation. Neither transcription
      product nor protein of ARH was detected in the fibroblasts of the homozygous
      patients. A single nucleotide polymorphism was discovered among the normal
      control subjects at position 604 (cytosine to thymine: ARH-604C to ARH-604T),
      which changes the proline residue at 202 to serine. Interestingly, ARH is caused
      by a mutation of cytosine to adenine at this same position. Both siblings
      exhibited fatty liver, which may also be related to this mutation.

PMID- 12788852
TI  - Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with
      high-density lipoprotein cholesterol level.
AB  - The serum level of high-density lipoprotein cholesterol (HDL-c), which protects
      against the development of atherosclerosis, is under genetic control. However,
      the genetic components responsible for the serum HDL-c level are yet to be
      determined. A recent knockout mouse study demonstrated that hepatocyte nuclear
      factor-1 alpha (HNF-1 alpha) is an essential transcriptional regulator of HDL-c
      metabolism. In this study, the association of an HNF-1 alpha gene polymorphism,
      isoleucine (Ile) 27 leucine (Leu), with lipid parameters, in particular with
      serum HDL-c level, was studied in 356 unrelated Japanese men. Though no
      significant difference was observed in total cholesterol and triglyceride levels
      among the three genotypes, the serum HDL-c level was significantly associated
      with the genotype (P < 0.01, trend test). Subjects with the Ile/Ile genotype had
      low serum HDL-c levels, and those with the Leu/Leu genotype had high serum HDL-c
      levels. These results demonstrate that the HNF-1 alpha gene locus is associated
      with serum HDL-c level and suggest that the Ile27 allele is a risk marker for
      atherosclerosis.

PMID- 12788853
TI  - Quantitative determination of estradiol fatty acid esters in lipoprotein
      fractions in human blood.
AB  - According to experimental studies, 17 beta-estradiol associates with lipoproteins
      in blood in the form of fatty acid esters. However, concentrations of endogenous
      estradiol esters in human lipoprotein fractions have not been previously
      reported. We investigated the distribution of estradiol fatty acid esters between
      plasma lipoproteins in 10 healthy women during late pregnancy. Following
      extraction from serum and ultracentrifugally isolated, gel-filtered lipoproteins,
      estradiol esters were separated from nonesterified estradiol by column
      chromatography. After saponification and chromatographic purification of the
      estradiol ester fraction, the concentration of hydrolyzed esters was determined
      by estradiol time-resolved fluoroimmunoassay. Of total serum estradiol, a mean of
      0.7% (549 pmol/liter, n = 10) was in the form of fatty acid esters. Estradiol
      fatty acid ester concentrations measured in serum and lipoprotein fraction
      correlated positively (n = 10; r = 0.98; P < 0.001). The majority of lipoprotein
      estradiol esters, 54%, was recovered in high-density lipoprotein, and 28% in low
      density lipoprotein fraction. Most lipoprotein fractions contained undetectable
      amounts of nonesterified estradiol (< 36 pmol/liter). In conclusion, our results
      indicate that estradiol fatty acid esters are mostly bound by lipoproteins in
      blood in vivo.

PMID- 12788854
TI  - The effects of depot long-acting somatostatin analog on central aortic pressure
      and arterial stiffness in acromegaly.
AB  - Acromegaly is associated with increased cardiovascular risk. Although
      conventional risk factors such as glucose intolerance, hypertension, and
      dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I
      excess on the vasculature. To study the effects of GH excess on the vasculature,
      we have assessed arterial stiffness in acromegalic subjects with and without
      active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on
      vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6
      females) and 8 healthy controls were studied. Of the acromegalic subjects, eight
      had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B).
      The three groups were age, sex, and blood pressure matched. Group A subjects were
      restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was
      assessed by analyzing central arterial pressure waveforms derived from measured
      radial artery waveforms. This allowed determination of the augmentation of
      central pressure and the augmentation index. Lipids, glucose, and IGF-I were also
      measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index
      was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22
      +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in
      group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9
      nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I
      concentration was identified as a strong independent predictor of the
      augmentation index (beta = 0.50; P = 0.007). There were no significant
      differences in aortic systolic pressure, aortic diastolic pressure, lipids, or
      glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of
      augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6
      months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced
      from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months
      (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion,
      acromegaly is associated with changes in the central arterial pressure waveform,
      suggesting large artery stiffening. This may have important implications for
      cardiac morphology and performance in acromegaly as well as increasing the
      susceptibility to atheromatous disease. Large artery stiffness is reduced in
      cured acromegaly and partially reversed after pharmacological treatment of active
      disease.

PMID- 12788855
TI  - Prevalence and predictors of coronary artery calcification in women with
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS), a common endocrine disorder of reproductive
      aged women, is associated with multiple risk factors for coronary heart disease
      (CHD), such as diabetes mellitus, dyslipidemia, visceral obesity, and
      hypertension. However, premature coronary atherosclerosis has not been
      demonstrated in PCOS women. Electron beam computed tomography (EBCT)
      noninvasively measures coronary artery calcium (CAC), a marker for coronary
      atherosclerosis. We measured CAC by EBCT in 30- to 45-yr-old premenopausal PCOS
      women and compared the results to CAC in 1) recruited normal ovulatory volunteers
      matched for age and weight to the PCOS cohort, and 2) community-dwelling women of
      similar age in an extant coronary calcium database. Healthy, community-dwelling,
      ovulatory controls (n = 71) were matched by age and body mass index (BMI) to PCOS
      women (n = 36). Women with diabetes or known CHD were excluded. Subjects
      underwent EBCT scanning, oral glucose tolerance testing, and CHD risk factor
      assessment. PCOS women had significantly higher levels of serum total and low
      density lipoprotein cholesterol and testosterone levels than matched controls.
      PCOS and control women were obese and had a greater mean BMI than community
      dwelling women (33 kg/m(2) for PCOS vs. 31 kg/m(2) for control; P < 0.001). CAC
      was more prevalent in PCOS women (39%) than in matched controls (21%; odds ratio,
      2.4; P = 0.05) or community-dwelling women (9.9%; odds ratio, 5.9; P < 0.001).
      BMI, waist circumference, and total and low density lipoprotein cholesterol
      levels predicted CAC prevalence after adjustment for BMI. CAC is more prevalent
      in PCOS women than in obese or nonobese women of similar age. PCOS women are at
      increased risk for atherosclerosis and should be targeted for primary prevention
      of CHD.

PMID- 12788856
TI  - Short-term effects of growth hormone on body composition as a predictor of
      growth.
AB  - The objective of this study was to investigate whether short-term changes in
      metabolism, as a result of GH therapy, could be used to predict its growth effect
      after 1 yr. Twenty-eight children (8.7 +/- 2.8 yr) were selected, based on
      anthropometric criteria characterizing GH-deficient patients. In addition, 21
      healthy, age- and sex-matched controls (8.9 +/- 3.1 yr) were included. Total body
      water (TBW) and height were measured before and at 6 wk and 1 yr after the start
      of treatment. After 1 yr of treatment, patients were divided into good and poor
      responders, based on a change in height of at least 0.7 SD. Because individuals
      of different heights were compared, changes in TBW after 6 wk were corrected for
      height(2), in accordance with the body mass index. Eighty percent of the children
      who showed a good response to GH therapy had a change in TBW divided by height(2)
      exceeding the 2 SD reference line of the controls. In contrast, poor responders
      did not differ from controls. Maximum GH concentrations found during endocrine
      tests were not significantly different between good and poor responders. Changes
      in body composition data, after 6 wk, proved valuable in identifying good
      responders to GH therapy.

PMID- 12788857
TI  - Increased pulse wave velocity associated with reduced calcaneal quantitative
      osteo-sono index: possible relationship between atherosclerosis and osteopenia.
AB  - Although the associations between arterial calcification or advanced
      atherosclerosis and osteopenia have been well documented, it is not clear whether
      the one is the result of the other or they coprogress from the early stages
      through common mechanisms. Thus, we measured pulse wave velocity (PWV), which
      reflects earlier phase atherosclerosis, and osteo-sono assessment index (OSI),
      which correlates with bone mineral density, in 7865 Japanese subjects (4183 males
      and 3682 females, aged 50 +/- 12 yr) and analyzed their association. PWV was
      determined by the volume rendering method; OSI was measured by the calcaneal
      quantitative ultrasound method. We evaluated the influence of age, gender,
      menopausal state, and established atherosclerotic risk factors on this
      association. In a linear regression analysis, OSI negatively correlated with PWV
      in both genders, and this association was more prominent in females (r = -0.38, P
      < 0.01) than in males (r = -0.17, P < 0.01). In females, this relationship was
      stronger after the menopause. In a multivariate analysis, PWV was significantly
      associated with OSI independent of age and conventional atherosclerotic risk
      factors. In females, this association was independent from menopause. These
      results suggest that common or related mechanisms, which may be accelerated after
      menopause, control both atherosclerosis and osteoporosis from the early stages.

PMID- 12788858
TI  - Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas
      as a potential marker for discriminating benign versus malignant tumors.
AB  - EM66 is a novel secretogranin II-derived peptide present in chromaffin cells of
      the human adrenal gland. The aim of the present study was to investigate the
      possible occurrence of EM66 in benign and malignant pheochromocytomas.
      Immunohistochemical labeling using specific antibodies revealed intense staining
      in both benign and malignant tumors. Coincubation of pheochromocytoma slices with
      EM66 and tyrosine hydroxylase antibodies showed that the immunostaining was
      restricted to chromaffin cells. RIA experiments indicated that serial dilutions
      of extracts of benign and malignant tumors generated displacement curves that
      were parallel to those produced by recombinant EM66. RIA quantification revealed
      concentrations of EM66 immunoreactivity ranging from 3.2-210 ng/mg protein
      (median = 25.6 ng/mg protein) in benign pheochromocytomas, and from 2.9-6.3 ng/mg
      protein (median = 3.8 ng/mg protein) in malignant tumors. The EM66-like
      immunoreactivity contained in the pheochromocytoma extracts was characterized by
      HPLC analysis combined with RIA detection. All of the benign and malignant tumors
      examined exhibited a single immunoreactive peak coeluting with recombinant EM66.
      These data indicate that the secretogranin II-derived peptide EM66 is generated
      in human tumoral chromaffin tissue. The significant difference in EM66
      concentrations observed between benign and malignant pheochromocytomas suggests
      that measurement of EM66 levels may help identifying patients with higher risk of
      progression of such tumors.

PMID- 12788859
TI  - Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo
      controlled trial.
AB  - Hypothalamic obesity is a devastating complication in children surviving brain
      tumors and/or cranial irradiation. These subjects are thought to exhibit
      autonomic dysregulation of the beta-cell, with insulin hypersecretion in response
      to oral glucose tolerance testing (OGTT). We report the results of a randomized,
      double-blind, placebo-controlled trial of octreotide therapy for pediatric
      hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass
      index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.)
      or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/
      0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs.
      +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin
      response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM
      after placebo (P = 0.034). Improvement in physical activity by parent report was
      noted with octreotide, but not placebo (P = 0.03). For the octreotide group,
      changes in quality of life positively correlated with changes in insulin response
      (P = 0.041). Complications and adverse events were mild and self-limited. These
      data demonstrate the beneficial effects of octreotide in pediatric hypothalamic
      obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved
      quality of life correlated with the degree of insulin suppression. Octreotide was
      safe and well tolerated.

PMID- 12788860
TI  - Changes in serum leptin in lean and obese subjects with acute hyperglycemic
      crises.
AB  - We aimed to determine the effect of insulin replacement on serum leptin
      concentration in lean and obese patients with diabetic ketoacidosis (DKA). We
      compared serial leptin levels in 52 patients with DKA, 14 obese subjects with
      hyperglycemia, and 52 nondiabetic control subjects. Leptin levels on admission
      were significantly decreased in lean and obese patients with DKA and/or
      hyperglycemia compared with weight- and gender-matched controls. Insulin therapy
      resulted in a significant increase in leptin levels within 4 h, with peak
      stimulation at 12 h. Leptin levels on admission and at resolution of
      hyperglycemia were higher in obese DKA (9.7 +/- 2 ng/ml and 26.5 +/- 5 ng/ml,
      respectively; P < 0.001) and obese hyperglycemia subjects (11.9 +/- 4 ng/ml vs.
      24.4 +/- 2 ng/ml; P < 0.001) than in lean DKA subjects (5.3 +/- 0.3 ng/ml and
      10.1 +/- 2 ng/ml; P < 0.001). We conclude that insulin treatment in patients with
      acute hyperglycemic crises is followed by rapid and significant increase in
      leptin concentration, and this increase is more discernible in obese subjects.
      The low serum leptin level on admission in subjects with hyperglycemic crises may
      be the result of impaired adipocyte glucose utilization due to insulin deficiency
      and/or to increased catecholamine levels.

PMID- 12788861
TI  - Serum androgen bioactivity in cryptorchid and noncryptorchid boys during the
      postnatal reproductive hormone surge.
AB  - The first postnatal months of life in boys are characterized by activation of the
      hypothalamic-pituitary-testicular axis that results in the well depicted surge of
      reproductive hormones. Serum testosterone levels at that time are high, but
      infants do not display signs of virilization, and subsequently there is only
      indirect evidence that circulating androgens during the surge are biologically
      active. We used a recombinant cell bioassay to determine serum androgen
      bioactivity in 80 3-month-old boys born after full-term pregnancies (37-42 wk) in
      whom localization of the testes was determined by palpation after birth and at a
      mean age of 3 months. At that age, serum androgen bioactivity ranged from less
      than 0.8 to 1.9 nM testosterone equivalents and correlated with serum
      testosterone concentration (r = 0.71; P < 0.0001; n = 34), free androgen index (r
      = 0.80; P < 0.0001; n = 34), age (r = -0.29; P < 0.01; n = 80), and localization
      of the testes (r = -0.24; P < 0.05; n = 80). Moreover, all boys in this study
      with detectable androgen bioactivity (n = 26) had testes located in scrotal or
      high scrotal position (n = 64), whereas all boys (n = 16) with at least 1
      suprascrotal, inguinal, or nonpalpable testis had nonmeasurable androgen
      bioactivity in serum (P < 0.01). We conclude that 3-month-old boys are exposed to
      biological effects of androgens during the postnatal activation of the
      hypothalamic-pituitary-testicular axis, and that this exposure may be reduced in
      boys with at least 1 testis located superior to the scrotum.

PMID- 12788862
TI  - Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat
      mass in nonobese adolescents with ovarian hyperandrogenism.
AB  - Ovarian hyperandrogenism is a common disorder often presenting post menarche with
      anovulatory oligomenorrhea and signs of androgen excess. Associated
      hyperinsulinemic insulin resistance, dyslipidemia, and central fat excess herald
      long-term disease risk. Combined antiandrogen (flutamide 250 mg/d) and insulin
      sensitizing (metformin) therapy has beneficial effects, in particular on
      dyslipidemia and androgen excess in young women. We studied the effects of low
      dose flutamide-metformin combination on metabolic variables and body composition
      in adolescent girls with ovarian hyperandrogenism. Thirty teenage girls (age
      range, 13.6-18.6 yr) with hyperinsulinemic hyperandrogenism participated in a 12
      month pilot study with a 3-month off-treatment phase and a 9-month treatment
      phase (randomized sequence) on combined flutamide (125 mg/d) and metformin (1275
      mg/d). Body composition was assessed by dual-energy x-ray absorptiometry;
      endocrine-metabolic state and ovulation rate were screened every 3 months.
      Insulin sensitivity was assessed by homeostasis model assessment (HOMA).
      Overnight GH and LH profiles were obtained pretreatment and after 6 months on
      treatment (n = 8). Over the 3-month pretreatment control phase (n = 14) all study
      indices were unchanged. Flutamide-metformin treatment (n = 30) was followed
      within 3 months by marked decreases in hirsutism score and serum androgens, by a
      more than 50% increase in insulin sensitivity and by a less atherogenic lipid
      profile (all P < 0.0001). After 9 months on flutamide-metformin, body fat
      decreased by 10%, with a preferential 20% loss of abdominal fat; conversely lean
      body mass increased, and total body weight remained unchanged; ovulation rate
      increased from 7-87% after 9 months. Baseline GH hypersecretion and elevated
      serum IGF-1 normalized after 6 months on flutamide-metformin. Within 3 months
      post treatment (n = 16), a rebound was observed for all assessed indices. In
      conclusion, in teenage girls with ovarian hyperandrogenism, low-dose combined
      flutamide-metformin therapy attenuated a spectrum of abnormalities, including
      insulin resistance and hyperlipidemia. Improved insulin sensitivity and reduced
      androgen activity led to a marked redistribution of body fat and lean mass,
      resulting in a more feminine body shape.

PMID- 12788863
TI  - Fat-free body mass is the most important body composition determinant of 10-yr
      longitudinal development of lumbar bone in adult men and women.
AB  - The purpose of this study was to analyze the longitudinal relationship between
      body composition and lumbar bone mineral density (LBMD) and lumbar bone mineral
      content (LBMC) in (young) adults over a 10-yr period. The data are from the
      Amsterdam Growth and Health Longitudinal Study. Two hundred twenty-five men and
      241 women were measured at 27, 32, and/or 36 yr of age. Nine body composition
      components were explored: total body weight, standing height, body mass index,
      waist circumference, hip circumference, waist to hip ratio, sum of four
      skinfolds, fat mass, and fat-free mass (FFM). Stratified analyses were performed
      by gender and adjustment was made for physical activity and calcium intake.
      Univariate multilevel analyses indicated that FFM was significantly positively
      related to the 10-yr development of both LBMD and LBMC in both sexes. Total body
      weight, standing height, and body mass index also showed a significant positive
      univariate relationships with LBMD and LBMC in both sexes, fat mass only with
      female LBMD. All best predictive multiple regression models included FFM,
      explaining 4-27% of the variation in bone mineral over this 10-yr period. Because
      FFM can be interpreted as a proxy for skeletal muscle mass, these results
      indicate the importance of muscle contractions on bone to increase bone strength
      in (young) adults.

PMID- 12788864
TI  - The Impact of congenital, severe, untreated growth hormone (GH) deficiency on
      bone size and density in young adults: insights from genetic GH-releasing hormone
      receptor deficiency.
AB  - GH and IGF-I have well recognized effects on bone elongation during development,
      but their importance for bone mineralization and structure during the growth
      phase are less well understood. Because children with GH deficiency are generally
      treated with GH, little detailed information exists in humans about the effects
      of long-term GH deficiency on bone development. The recently described syndrome
      of genetic GHRH receptor deficiency in Pakistan (dwarfism of Sindh) affords a
      unique opportunity to examine the question of GH deficiency on bone development
      because the affected patients have congenital, severe, isolated GH deficiency,
      which had never been treated because of societal reasons. We performed dual
      energy x-ray absorptiometry scans in four adult males (age, 23-30 yr) to address
      the question of bone mineralization. Areal bone mineral density (BMD) was low
      (mean Z scores: -3.3, -2.1, -3.7, and -1.7) in the lumbar spine, femoral neck,
      forearm, and total skeleton, respectively. This low areal BMD is in part caused
      by the small bone size in these dwarfed patients. When corrected for size,
      volumetric BMD (bone mineral apparent density) was normal to near normal (mean Z
      scores: -1.2, +0.8, and +0.8 for lumbar spine, femoral neck and total skeleton,
      respectively). We conclude that GH/IGF-I deficiency has relatively little impact
      on bone mineralization during the bone accretion phase. This is in marked
      contrast to their effect on bone elongation and overall bone size.

PMID- 12788865
TI  - Adiponectin levels in women with polycystic ovary syndrome.
AB  - Serum adiponectin levels were evaluated in 60 women with polycystic ovary
      syndrome (PCOS), 30 normal-weighted and 30 obese women, and 60 healthy women age
      and body mass index (BMI) matched with the patients. The homeostasis model
      assessment (HOMA) score was also calculated. Both in PCOS and controls, serum
      adiponectin levels were significantly (P < 0.05) lower in obese than normal
      weight women, without any difference between PCOS and controls. The HOMA score
      was significantly (P < 0.05) higher in obese than normal-weight women both in
      PCOS and controls; additionally, the HOMA score was significantly (P < 0.05)
      higher in normal-weight PCOS than normal-weight controls. Both in PCOS and
      controls, adiponectin levels were significantly correlated with BMI (r = -0.51, P
      < 0.01 in PCOS; r = -0.45, P < 0.01 in controls) and HOMA values (r = -0.39, P <
      0.05 in PCOS; r = -0.35, P < 0.05 in controls); HOMA was correlated with BMI (r =
      0.51, P < 0.01 in PCOS, r = 0.61, P < 0.001 in controls). In conclusion, our
      results confirm that adiponectin concentrations change according to variations of
      fat mass. They further suggest that insulin sensitivity per se probably does not
      play any pivotal role in the control of adiponectin levels in PCOS women.

PMID- 12788866
TI  - Follow-up of 68 children with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency: relevance of genotype for management.
AB  - The phenotype of congenital adrenal hyperplasia (CAH) varies greatly. The purpose
      of this study was to optimize diagnosis and follow-up by comparing phenotype with
      genotype. Sixty-eight patients with CAH due to 21-hydroxylase deficiency were
      studied by clinical, hormonal, and molecular genetic methods. Patients were
      classified according to predicted mutation severity: group 0, null mutation
      (17.6%); group A, homozygous for IVS2 splice mutation or compound heterozygous
      for IVS2 and null mutations (33.8%); group B, homozygous or compound heterozygous
      for I172N mutation (14.7%); group C, homozygous or compound heterozygous for
      V281L or P30L mutations (26.5%); and group D, mutations with unknown enzyme
      activity (7.4%). All group 0 and A patients had the salt-wasting form, and group
      C had nonclassical forms. Group B included five salt-wasting and five simple
      virilizing forms. Groups 0 and A were younger at diagnosis (P < 0.02), and
      females were more virilized than those in group B. Group B had higher basal
      plasma 17-hydroxyprogesterone (564 +/- 162 nmol/liter) and testosterone (11 +/- 3
      nmol/liter) levels than group C [59 +/- 13 nmol/liter (P < 0.001) and 1.4 +/- 0.2
      nmol/liter (P < 0.005), respectively]. Hydrocortisone doses given to groups 0, A,
      and B were similar at all ages, but lower in group C (P < 0.01). Final height was
      below target height in classical (n = 16; -2 +/- 0.2 SD score; P < 0.02) and
      nonclassical (n = 11; -1.2 +/- 0.4 SD score; P < 0.03) forms. The severity of the
      genetic defects and the clinical-laboratory features are well correlated.
      Genotyping, combined with neonatal screening and optimal medical and surgical
      treatment, can help in the management of CAH.

PMID- 12788867
TI  - The value of the low-dose dexamethasone suppression test in the differential
      diagnosis of hyperandrogenism in women.
AB  - We studied 211 hyperandrogenic women with respect to clinical presentation, basal
      androgen levels, and the degree of cortisol and androgen suppression during a 48
      h low-dose (2 mg) dexamethasone-suppression test (LDDST) to exclude ovarian and
      adrenal tumors. In 42 women with elevated testosterone levels, 21 of whom failed
      to suppress testosterone during the LDDST, the response of serum androgen levels
      during a 4-wk administration of 7.5 mg prednisolone in a reverse circadian
      regimen was also assessed. These results were compared with an additional 17
      patients with histologically proven androgen-secreting tumors. Clinical
      presentation alone was suggestive of a virilizing tumor in 70% of patients with
      tumors. Serum testosterone, although occasionally only marginally elevated, was
      the sole androgen that was elevated in every patient with a tumor. After the
      LDDST, none of the patients with tumors obtained either a greater than 40%
      reduction or normalization of the previously elevated testosterone levels,
      whereas 88% of patients with nontumorous hyperandrogenism showed either
      normalization or suppression of more than 40%. With one exception, all of the
      patients with nontumorous hyperandrogenism who showed inadequate suppression of
      testosterone during the LDDST, and were treated with prednisolone, normalized the
      previously elevated androgens after 1 month of administration. In summary, in
      women presenting with hyperandrogenism, lack of testosterone suppression during
      the LDDST is associated with 100% sensitivity and 88% specificity in
      distinguishing patients with ovarian and adrenal androgen-secreting tumors from
      patients with nontumorous hyperandrogenism in this small series. The LDDST is an
      easy to perform screening test that can also identify causes of hyperandrogenism
      due to altered glucocorticoid secretion.

PMID- 12788868
TI  - RET codon 634 mutations in multiple endocrine neoplasia type 2: variable clinical
      features and clinical outcome.
AB  - Since the establishment of a protocol for molecular analysis of hereditary
      medullary thyroid carcinoma (MTC) in southern Brazil, in 1997, 17 independent
      families with RET germline mutation have been identified. Because neither
      molecular diagnosis nor the pentagastrin test were available before the
      establishment of this protocol, we had the opportunity to observe a large number
      of patients in whom the disease has evolved naturally without medical
      intervention, namely prophylactic thyroidectomy. We observed a wide spectrum in
      terms of clinical presentation and natural course of the disease even among
      genetically related individuals. Sixty-nine individuals from 12 different
      families presented a codon 634 mutation, the most prevailing missense mutation in
      our series. The specific mutations identified were C634Y (n = 49), C634R (n =
      13), and C634W (n = 7). Individuals with the C634R mutation presented
      significantly more distant metastases at diagnosis than subjects with the C634Y
      or C634W mutations (54.5% vs. 19.4% vs. 14.3%, respectively, P = 0.03). Further
      analysis of the estimated cumulative frequency of lymph node and/or distant
      metastases by Kaplan-Meier curves showed that the appearance of lymph nodes and
      metastases occurred later in patients with C634Y than in those with C634R (P =
      0.001). Our results suggest that specific nucleotide and amino acid exchanges at
      codon 634 might have a direct impact on tumor aggressiveness in MEN 2A syndrome.

PMID- 12788869
TI  - Autosomal dominant hyperostosis/osteosclerosis with high serum alkaline
      phosphatase activity.
AB  - We studied eight affected and four unaffected individuals from a Colombian family
      with autosomal dominant diffuse high bone density. Affected individuals have
      normal, proportional height and high serum alkaline phosphatase activity.
      Radiographically, affected members exhibit generalized, symmetrically diffuse
      endosteal hyperostosis of the long bones and skull with narrow medullary cavities
      and loss of the diploe, respectively. There is no periosteal reaction or
      decreased hematopoiesis. Furthermore, osteosclerosis affects vertebral bodies,
      ribs, pelvis, mandible, clavicles, and scapulae. Bone mineral density is 2.4-7.3
      SD above the mean for age and gender in affected individuals. Affected vs.
      unaffected individuals' Z-scores were (mean +/- SD) 5.03 +/- 1.77 vs. 0.08 +/-
      0.97, respectively, P = 0.0004). Three affected subjects older than 40 yr old
      lost bone mass in 6 yr. No dysmorphism, abnormal facial features, bone fractures,
      or cranial nerve involvement was found. The pattern of inheritance, the absence
      of asymmetries and malformations, the increased serum alkaline phosphatase, the
      peak bone mass that appears to decrease physiologically with age, and the
      involvement of cortical and trabecular bone suggest a new variant of
      hyperostosis/osteosclerosis that affects the entire skeleton.

PMID- 12788870
TI  - Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false
      positive test results.
AB  - Measurements of plasma normetanephrine and metanephrine provide a highly
      sensitive test for diagnosis of pheochromocytoma, but false-positive results
      remain a problem. We therefore assessed medication-associated false-positive
      results and use of supplementary tests, including plasma normetanephrine
      responses to clonidine, to distinguish true- from false-positive results. The
      study included 208 patients with pheochromocytoma and 648 patients in whom
      pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48
      patients with and 49 patients without the tumor. Tricyclic antidepressants and
      phenoxybenzamine accounted for 41% of false-positive elevations of plasma
      normetanephrine and 44-45% those of plasma and urinary norepinephrine. High
      plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios
      were strongly predictive of pheochromocytoma. Lack of decrease and elevated
      plasma levels of norepinephrine or normetanephrine after clonidine also confirmed
      pheochromocytoma with high specificity. However, 16 of 48 patients with
      pheochromocytoma had normal levels or decreases of norepinephrine after
      clonidine. In contrast, plasma normetanephrine remained elevated in all but 2
      patients, indicating more reliable diagnosis using normetanephrine than
      norepinephrine responses to clonidine. Thus, in patients with suspected
      pheochromocytoma and positive biochemical results, false-positive elevations due
      to medications should first be eliminated. Patterns of biochemical test results
      and responses of plasma normetanephrine to clonidine can then help distinguish
      true- from false-positive results.

PMID- 12788871
TI  - Painful Hashimoto's thyroiditis as an indication for thyroidectomy: clinical
      characteristics and outcome in seven patients.
AB  - Patients with chronic lymphocytic thyroiditis, or Hashimoto's thyroiditis (HT),
      usually present with goiter, hypothyroidism, or both. Thyroid pain and tenderness
      are rare and suggest an alternative diagnosis of subacute granulomatous
      thyroiditis or other forms of thyroiditis. We report seven patients with painful
      HT who had temporary or no relief from L-thyroxine replacement or steroid
      treatment and required surgical intervention for unremitting pain. Antithyroid
      antibodies were elevated in all except one patient, in whom fine-needle
      aspiration and surgical pathology were diagnostic of HT. All patients underwent
      either a subtotal or near-total thyroidectomy. Pathology showed lymphocytic
      thyroiditis in all specimens, with varying degrees of fibrosis. Giant cells and
      granulomas characteristic of subacute thyroiditis were not seen. After surgery,
      four patients obtained total and permanent relief of pain after subtotal (two
      patients) or near total (two patients) thyroidectomy, whereas one patient had
      minimal residual discomfort. One patient had relapse of pain, despite adjunct
      radioiodine ablation. In this patient with documented total thyroid ablation but
      persistent pain, the overall clinical picture suggested a strong psychological
      element in her medical problem. In conclusion, thyroidectomy is an uncommon but
      necessary therapy for patients with painful HT not responding to medical therapy.

PMID- 12788872
TI  - AA2500 testosterone gel normalizes androgen levels in aging males with
      improvements in body composition and sexual function.
AB  - Testosterone replacement in hypogonadal men improves body composition, mood, and
      sexual functioning. In this 90-d study, we compared the pharmacokinetics and
      treatment effectiveness of a topical testosterone gel (AA2500) at two
      concentrations, 50 mg/d and 100 mg/d, to a testosterone patch and placebo gel in
      406 hypogonadal men. Pharmacokinetic profiles were obtained, body composition was
      measured, and mood and sexual function were monitored. AA2500 treatments resulted
      in dose-dependent improvements in all pharmacokinetic parameters, compared with
      testosterone patch and placebo. Mean average concentrations at d 90 T were 13.8,
      17.1, 11.9, and 7.3 nmol/liter for 50 mg/d AA2500, 100 mg/d AA2500, testosterone
      patch, and placebo, respectively. At d 90, the 100 mg/d AA2500 treatment improved
      lean body mass by 1.7 kg and percentage of body fat by 1.2% to a significantly
      greater degree than either control treatment. Significant improvements in
      spontaneous erections, sexual desire, and sexual motivation were also evidenced
      with the 100 mg/d AA2500 dose in comparison with placebo. Testosterone gel was
      well tolerated; however, the testosterone patch resulted in a high rate of
      application site reactions. Overall, AA2500 is an effective, well tolerated
      treatment for hypogonadism.

PMID- 12788873
TI  - Genetic modification of risk assessment based on staging of preclinical type 1
      diabetes in siblings of affected children.
AB  - We set out to study the association between human leukocyte antigen-defined
      genetic disease susceptibility and the stage of preclinical type 1 diabetes and
      whether genetic predisposition affects the natural course of preclinical diabetes
      in initially nondiabetic siblings of affected children. A total of 701 initially
      unaffected siblings were graded into four stages of preclinical type 1 diabetes
      based on the initial number of disease-associated autoantibodies detectable close
      to the time of diagnosis of the index case: no prediabetes (no antibodies), early
      (one antibody specificity), advanced (two antibodies), and late prediabetes
      (three or more antibodies). Another classification system covering 659 siblings
      was based on a combination of the initial number of antibodies and the first
      phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies),
      early (one antibody specificity, normal FPIR), advanced (two or more antibodies,
      normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic
      susceptibility to type 1 diabetes was defined by human leukocyte antigen identity
      and DR and DQ genotypes. There was a higher proportion of siblings with late
      prediabetes initially among those with strong genetic disease susceptibility than
      among those with decreased genetic predisposition (16.7% vs. 0.5%; P < 0.001 for
      DQB1 genotypes according to the first classification), whereas there was a higher
      proportion of siblings with no signs of prediabetes among those with genotypes
      conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1
      genotypes; P < 0.001 according to the first classification). Autoantibodies alone
      were more sensitive in the prediction of future diabetes in siblings than when
      combined with genetic susceptibility. Genetic susceptibility played a role in
      whether the initial prediabetic stage progressed (progression in 29.6% of the
      high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes
      conferring decreased risk; P < 0.001 according to the first classification) and
      whether overt type 1 diabetes became manifest or not. Genetic susceptibility has
      an impact on both the initiation and progression of the autoimmune process
      leading to clinical diabetes in siblings of affected children.

PMID- 12788874
TI  - Interleukin-1 beta stimulates progesterone production by in vitro human luteal
      cells: evidence of a mediatory role of prostaglandins.
AB  - We have investigated whether IL-1 beta, a cytokine with an important role in
      ovarian physiology, is also involved in progesterone (P) synthesis in human
      luteal cells, and whether this effect is mediated via the cyclooxygenase (COX)
      pathway. Human luteal cells were cultured for 24 h in the presence of IL-1 beta
      (0.01-10 ng/ml), given alone or in combination with human chorionic gonadotropin
      (100 ng/ml), indomethacin (1 micro g/ml), or P (100 ng/ml). We observed a
      significant increase in prostaglandin (PG)release after IL-1 beta treatment; the
      cytokine was more effective on PGE(2) than PGF(2 alpha) release. The effect of IL
      1 beta was abolished by human chorionic gonadotropin, which had no action on
      basal PG levels when given alone; in contrast, P reduced basal, but not IL-1 beta
      stimulated, PG production. Treatment with the human IL-1 receptor antagonist was
      associated with a decrease in both basal and IL-1 beta-stimulated PG production.
      Moreover, IL-1 beta induced a concentration-dependent increase in P production
      and release, an effect counteracted by the COX inhibitor indomethacin. In
      conclusion, our data show the ability of IL-1 beta to influence P secretion via
      the COX pathway, thereby suggesting a possible luteotropic role in human ovary
      based on an autocrine-paracrine mechanism.

PMID- 12788875
TI  - Variability of vascular endothelial growth factor in normal human breast tissue
      in vivo during the menstrual cycle.
AB  - Exposure to sex steroids increases the risk of breast cancer, but the mechanisms
      are poorly understood. Angiogenesis is crucial in tumor development and
      progression. Very little is known about the regulation of angiogenesis in the
      normal breast. Vascular endothelial growth factor (VEGF) has a key stimulatory
      role in angiogenesis. Interferon-inducible protein 10 (IP-10) is a potent
      inhibitor of angiogenesis in vivo. These factors function in autocrine/paracrine
      pathways; therefore, direct measurements in the target tissue are needed. I
      measured VEGF and IP-10 in normal human breast tissue in situ in healthy women,
      using microdialysis, in the follicular and luteal phase of the menstrual cycle.
      In breast tissue, VEGF levels increased in the luteal phase, compared with the
      follicular phase (17.8 +/- 4 pg/ml to 34 +/- 9 pg/ml, P < 0.05). Plasma VEGF did
      not show a cyclic variation (10.6 +/- 2.8 pg/ml vs. 14.6 +/- 3.5 pg/liter, P =
      0.3). IP-10 levels did not vary during the menstrual cycle either in breast
      tissue (65 +/- 17 pg/ml vs. 75 +/- 21 pg/ml, P = 0.6) or in plasma (64 +/- 7
      pg/ml vs. 81 +/- 10 pg/ml, P = 0.06). The data suggests that, in the luteal
      phase, VEGF and IP-10, in the normal human breast, exhibit a proangiogenic
      profile. This may be one mechanism by which sex steroids contribute to breast
      cancer development.

PMID- 12788876
TI  - Blood glucose concentrations are reduced in children born small for gestational
      age (SGA), and thyroid-stimulating hormone levels are increased in SGA with
      blunted postnatal catch-up growth.
AB  - Fetal growth restriction is associated with an increased risk of developing
      insulin resistance and type 2 diabetes in adulthood. In addition, 10-20% of
      children born small for gestational age (SGA) do not achieve a normal final
      height. The purpose of this study was to investigate insulin sensitivity and
      endocrine status in SGA children, compared with that in children born appropriate
      for gestational age (AGA). Furthermore, within the SGA group, we aimed to relate
      postnatal growth to anthropometric, biochemical, and endocrine parameters. Eighty
      two SGA children (with a mean age of 8.6 +/- 3.5 yr) and 53 short-AGA children
      (with a mean age of 9.3 +/- 3.3 yr) were studied. A case-control study was
      carried out in 26 SGA and 26 short-AGA subjects. For each SGA subject, we
      selected a short-AGA child matched for sex, age (within 1 yr), pubertal status,
      body mass index (within 0.5 kg/m(2)), and height (within 0.25 z-score).
      Children's statures were corrected for their midparental height, and SGA children
      were subdivided into 2 groups: catch-up growth (CG) group (children with
      corrected height with at least 0 z-score); and non-CG (NCG) group (subjects with
      corrected height with less than 0 z-score). Comparing SGA with short-AGA
      subjects, no significant differences in fasting insulin, fasting glucose/insulin
      ratio, homeostasis assessment model for insulin resistance, and homeostasis
      assessment model-beta-cell values were observed. SGA children showed
      significantly reduced levels of glucose (4.4 +/- 0.6 vs. 4.9 +/- 0.6 mM, P <
      0.0001), total cholesterol (160.1 +/- 28.8 vs. 171.8 +/- 28.5 mg/dl, P = 0.02),
      and high-density-lipoprotein cholesterol (53.3 +/- 12.1 vs. 58 +/- 11.4 mg/dl, P
      = 0.02). The analysis of the subjects selected for the case-control study
      confirmed that SGA children did not have significant differences in the indices
      of insulin sensitivity but showed significantly lower glucose levels (4.4 +/- 0.7
      vs. 4.9 +/- 0.4 mM, P < 0.005). Subdividing the SGA group into CG (n = 25) and
      NCG (n = 57) children, we found that NCG children showed significantly higher
      levels of TSH (2.5 +/- 1.3 vs. 1.9 +/- 0.6 mU/liter, P = 0.002). Our data
      indicate that SGA children do not have altered insulin sensitivity when compared
      with auxologically identical AGA subjects but show a significant reduction of
      glucose concentrations. Whether the lower glucose levels are attributable to an
      early phase of augmented insulin sensitivity, as previously reported in animal
      models, has to be established. The finding of higher TSH concentrations in SGA
      children with blunted CG suggests that intrauterine reprogramming might involve
      thyroid function, which, in turn, might affect postnatal growth and cholesterol
      metabolism, eventually increasing the risk of cardiovascular disease.

PMID- 12788877
TI  - Incretin secretion in relation to meal size and body weight in healthy subjects
      and people with type 1 and type 2 diabetes mellitus.
AB  - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) are incretin hormones secreted in response to meal ingestion, thereby
      enhancing postprandial insulin secretion. Therefore, an attenuated incretin
      response could contribute to the impaired insulin responses in patients with
      diabetes mellitus. The aim of the present investigation was to investigate
      incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its
      dependence on the magnitude of the meal stimulus. Plasma concentrations of
      incretin hormones (total, reflecting secretion and intact, reflecting potential
      action) were measured during two meal tests (260 kcal and 520 kcal) in eight type
      1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic
      patients, and eight obese healthy subjects. Both in diabetic patients and in
      healthy subjects, significant increases in GLP-1 and GIP concentrations were seen
      after ingestion of both meals. The incretin responses were significantly higher
      in all groups after the large meal, compared with the small meal, with
      correspondingly higher C-peptide responses. Both type 1 and type 2 diabetic
      patients had normal GIP responses, compared with healthy subjects, whereas
      decreased GLP-1 responses were seen in type 2 diabetic patients, compared with
      matched obese healthy subjects. Incremental GLP-1 responses were normal in type 1
      diabetic patients. Increased fasting concentrations of GIP and an early enhanced
      postprandial GIP response were seen in obese, compared with lean healthy
      subjects, whereas GLP-1 responses were the same in the two groups. beta-cell
      sensitivity to glucose, evaluated as the slope of insulin secretion rates vs.
      plasma glucose concentration, tended to increase in both type 2 diabetic patients
      (29%, P = 0.19) and obese healthy subjects (22% P = 0.04) during the large meal,
      compared with the small meal, perhaps reflecting the increased incretin response.
      We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired
      insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is
      normal in type 1 diabetic patients; and 2) that it is possible to modulate the
      beta-cell sensitivity to glucose in obese healthy subjects, and possibly also in
      type 2 diabetic patients, by giving them a large meal, compared with a small
      meal.

PMID- 12788878
TI  - Novel interactions of adiponectin with the endocrine system and inflammatory
      parameters.
AB  - Several markers of chronic immune activation have been found in association with
      obesity and insulin resistance. We aimed to study the interaction of adiponectin
      with chronic inflammation and known components of the insulin resistance
      syndrome. Insulin sensitivity (minimal model analysis) and plasma soluble
      fractions of TNF-alpha receptor 1 (sTNFR1) and 2 (sTNFR2), adrenal and thyroid
      function, and adiponectin were evaluated in 68 apparently healthy subjects. An
      additional group of type 2 diabetic patients (n = 19) similarly studied, except
      for insulin sensitivity, were also included in the analysis. As reported by
      others, serum adiponectin concentrations were higher in women than in men (13.55
      +/- 9.79 vs. 8.64 +/- 7.83 mg/liter; P = 0.018). They were also higher in healthy
      subjects compared with diabetic patients (10.35 +/- 8.48 vs. 7.41 +/- 8.31
      mg/liter; P = 0.021). As expected also, circulating adiponectin was significantly
      associated with waist to hip ratio (r = -0.28; P = 0.013), diastolic blood
      pressure (r = -0.25; P = 0.027), fasting plasma high-density lipoprotein
      cholesterol (r = 0.35; P = 0.001), triglycerides (r = -0.37; P = 0.001), and
      insulin sensitivity (r = 0.30; P = 0.011). Additionally, subjects in the higher
      quartile of circulating adiponectin had lower sTNFR2 concentrations (3.05 vs.
      4.37 microg/liter; P = 0.012), a trend to lower sTNFR1 concentrations (1.76 vs.
      2.20 microg/liter; P = 0.055), higher concentration of serum morning cortisol
      (16.86 vs. 13.52 microg/dl; P = 0.027), and higher serum free T(4) levels (1.31
      vs. 1.20 ng/dl; P = 0.038). Multiple regression analysis models were constructed
      to predict adiponectin concentrations. Predictive variables in these models
      included insulin sensitivity, waist to hip ratio and free T(4), contributing to
      17%, 10%, and 8% of adiponectin variance, respectively, These findings suggest
      that circulating adiponectin differentially modulates insulin action and that
      thyroid-axis, inflammatory cytokines, and the adrenal cortex might intervene in
      this modulation.

PMID- 12788879
TI  - Normalization of glucose concentrations and deceleration of gastric emptying
      after solid meals during intravenous glucagon-like peptide 1 in patients with
      type 2 diabetes.
AB  - The effects of different i.v. doses of glucagon-like peptide 1 (GLP-1) on glucose
      homeostasis and gastric emptying were compared in patients with type 2 diabetes.
      Twelve patients with type 2 diabetes received three different infusion rates of
      GLP-1 (0.4, 0.8, and 1.2 pmol/kg x min) or placebo in the fasting state and after
      a solid test meal (containing [(13)C]octanoic acid). Blood was drawn for glucose,
      insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate
      was calculated from the (13)CO(2) excretion rates in breath samples. Statistics
      were determined using repeated measures ANOVA and Duncan's post hoc test. Plasma
      glucose concentrations were equally normalized with all GLP-1 doses (P < 0.001).
      Insulin and C-peptide concentrations dose-dependently rose during GLP-1 infusion
      in the fasting state (P < 0.05), but were dose-dependently reduced by GLP-1 after
      meal ingestion (P = 0.0031 and 0.0074, respectively). Glucagon secretion was
      suppressed with GLP-1. Gastric emptying was decelerated by GLP-1 in a dose
      dependent fashion (P < 0.001). Despite a dose-dependent stimulation of insulin
      secretion, glucose normalization can be achieved even with 0.4 pmol GLP-1/kg x
      min. Due to the dose-dependent inhibition of gastric emptying, lower GLP-1 doses
      than previously used may be as suitable for glucose control in patients with type
      2 diabetes.

PMID- 12788880
TI  - Mutation of IVS2 -12A/C>G in combination with 707-714delGAGACTAC in the CYP21
      gene is caused by deletion of the C4-CYP21 repeat module with steroid 21
      hydroxylase deficiency.
AB  - More than 90% of the cases of congenital adrenal hyperplasia are caused by
      mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are
      generated through intergenic recombination, termed apparent gene conversion, from
      the neighboring CYP21P pseudogene. Among them, mutation of the aberrant splicing
      donor site of IVS2 -12A/C>G at nucleotide (nt) 655 is believed to be a result
      derived from this mechanism and is the most prevalent case among all ethnic
      groups. However, mutation of 707-714delGAGACTAC rarely exists alone, although
      this locus is a distance of 53 nt away from IVS2 -12A/C>G. From the molecular
      characterization of the mutation of IVS2 -12A/C>G combined with 707
      714delGAGACTAC in patients with congenital adrenal hyperplasia, we found that it
      appeared to be in a 3.2-rather than a 3.7-kb fragment generated by Taq I
      digestion in a PCR product of the CYP21 gene. Interestingly, the 5' end region of
      such a CYP21 haplotype had CYP21P-specific sequences. Our results indicate that
      the coexistence of these two mutations is caused by deletion of the CYP21P, XA,
      RP2, and C4B genes and intergenic recombination in the C4-CYP21 repeat module.
      Surprisingly, this kind of the haplotype of the mutated CYP21 gene has not been
      reported as a gene deletion.

PMID- 12788881
TI  - Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis
      excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor
      genes.
AB  - Failure of the normal pattern of episodic secretion of GnRH from the hypothalamus
      results in the clinical syndrome of idiopathic hypogonadotropic hypogonadism
      (IHH), with failure of pubertal development and infertility. The only gene that
      has been implicated in normosmic IHH is the GnRH receptor gene (GNRHR), which
      accounts for 10% of cases. This report presents four families with autosomal
      recessive IHH, including a consanguineous pedigree from the Middle East. Defects
      within the genomic coding sequence of the GNRHR, and the GnRH gene itself, GNRH1,
      were excluded by temperature gradient gel electrophoresis, direct sequencing, and
      haplotypes created from simple sequence polymorphisms flanking the GNRH1 and
      GNRHR loci. We concluded that: 1) genetic analysis has excluded sequence
      variations in GNRH1 and GNRHR in four families with recessive IHH, suggesting the
      existence of a novel, as-yet-undiscovered gene for this condition, and 2) because
      mutation analysis of genomic coding sequence will fail to detect mutations deep
      within introns or regulatory regions, haplotype analysis is the preferred genetic
      methodology to eliminate the role of specific candidate genes.

PMID- 12788882
TI  - Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and
      messenger ribonucleic acid levels are associated with adiposity and insulinemia
      in Pima Indians and Caucasians.
AB  - Metabolic effects of cortisol may be critically modulated by glucocorticoid
      metabolism in tissues. Specifically, active cortisol is regenerated from inactive
      cortisone by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) in
      adipose and liver. We examined activity and mRNA levels of 11-HSD1 and tissue
      cortisol and cortisone levels in sc adipose tissue biopsies from 12 Caucasian (7
      males and 5 females) and 19 Pima Indian (10 males and 9 females) nondiabetic
      subjects aged 28 +/- 7.6 yr (mean +/- SD; range, 18-45). Adipose 11-HSD1 activity
      and mRNA levels were highly correlated (r = 0.51, P = 0.003). Adipose 11-HSD1
      activity was positively related to measures of total (body mass index, percentage
      body fat) and central (waist circumference) adiposity (P < 0.05 for all) and
      fasting glucose (r = 0.43, P = 0.02), insulin (r = 0.60, P = 0.0005), and insulin
      resistance by the homeostasis model (r = 0.70, P < 0.0001) but did not differ
      between sexes or ethnic groups. Intra-adipose cortisol was positively associated
      with fasting insulin (r = 0.37, P = 0.04) but was not significantly correlated
      with 11-HSD1 mRNA or activity or with other metabolic variables. In this cross
      sectional study, higher adipose 11-HSD1 activity is associated with features of
      the metabolic syndrome. Our data support the hypothesis that increased
      regeneration of cortisol in adipose tissue influences metabolic sequelae of human
      obesity.

PMID- 12788883
TI  - Specific pattern of RAS oncogene mutations in follicular thyroid tumors.
AB  - The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors
      according to malignancy and histology is controversial. Differences in
      methodology and histological classifications may explain discrepant results. To
      address this issue, we first performed a pooled analysis of 269 mutations
      garnered from 39 previous studies. Mutations proved significantly less frequent
      when detected with direct sequencing than without (12.3% vs. 17%). The rate of
      mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%.
      Mutations of codon 61 of N-RAS (N2) were significantly more frequent in
      follicular tumors (19%) than in papillary cancers (5%) and significantly more
      frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in
      codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations
      in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them
      were malignant. K-RAS mutations in exon 1 were found more often in papillary than
      follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special
      epidemiological circumstances. The second part of this study involved analysis of
      80 follicular tumors from patients living in Marseille (France) and Kiev
      (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of
      the three RAS genes. Common and atypical adenomas were separated using strict
      cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas
      and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and
      17.6% of atypical adenomas and follicular carcinomas, respectively. These results
      confirm the predominance of N2-RAS mutations in thyroid follicular tumors and
      their correlation with malignancy. They support the implication of N2-RAS
      mutations in the malignant progression of thyroid follicular tumors and the
      assumption that some atypical adenomas are precursors of follicular carcinomas.

PMID- 12788884
TI  - Insulin secretagogues, but not glucose, stimulate an increase in [Ca2+]i in the
      fetal human and porcine beta-cell.
AB  - Fetal pancreatic beta-cells release insulin poorly in response to glucose;
      however, the cellular mechanism for this is unknown. By using fura-2 to measure
      changes in the cytoplasmic free Ca(2+) concentration in beta-cells, we examined
      human/porcine fetal islet-like cell clusters (ICCs) and human adult islets for
      the presence of functional K(+)(ATP) and voltage-activated Ca(2+) ion channels.
      The effects of glucose, glyceraldehyde, leucine, KCl, and the channel effectors
      glipizide and BAY K8644 were studied. In fetal human/porcine ICCs and adult
      islets, KCl, glipizide, and BAY K8644 increased [Ca(2+)](i). Both glucose and
      glyceraldehyde increased [Ca(2+)](i) in islets but had no effect on ICCs. Leucine
      increased [Ca(2+)](i) in islets and porcine but not human ICCs. We hypothesize
      that the beneficial effect of leucine in fetal porcine, but not human ICCs, is
      attributable to time-dependent maturation of the beta-cells, because porcine ICCs
      examined were at 87% of the gestational period, and human ICCs were at 42%. Our
      data demonstrate that both K(+)(ATP) and voltage-activated Ca(2+) channels,
      required for glucose-stimulated increase in [Ca(2+)](i), are functional early in
      gestation. This suggests that the cause of the immaturity of fetal human/porcine
      beta-cells is at a more proximal step of glucose-induced metabolism than the
      channels on the cell surface.

PMID- 12788885
TI  - Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha
      reductase activity in women with polycystic ovary syndrome.
AB  - Hyperandrogenism, a main clinical feature of polycystic ovary syndrome (PCOS), is
      thought to result from enhanced ovarian and adrenal androgen generation. To
      investigate the contribution of peripheral steroidogenesis, we used an oral
      challenge with dehydroepiandrosterone (DHEA) and analyzed its downstream
      conversion toward androgens in eight women with PCOS (age, 20-32 yr; body mass
      index, 20-41 kg/m(2)) and eight healthy women matched for age and body mass
      index. They underwent frequent serum sampling and urine collection for 8 h on
      three occasions: at baseline, and after 4 d of dexamethasone (Dex; 4 x 0.5 mg/d),
      followed by ingestion of 100 mg DHEA or placebo. Dex induced similar significant
      suppression of circulating steroids in both groups. The oral DHEA challenge led
      to similar significant increases in the area under the concentration-time curve
      (0-8 h after Dex) of serum DHEA, DHEA sulfate, androstenedione, and testosterone.
      However, after oral DHEA, PCOS women had significantly higher increases in serum
      5 alpha-dihydrotestosterone (P < 0.01), its main metabolite androstanediol
      glucuronide (P < 0.05), and the 5 alpha-reduced urinary androgen metabolite
      androsterone (P < 0.05). PCOS women also had significantly higher baseline
      excretion of 5 alpha-reduced glucocorticoid (P < 0.01) and mineralocorticoid
      metabolites (P < 0.05). Taken together, these data indicate enhanced peripheral 5
      alpha-reductase activity in PCOS. Thus, not only ovary and adrenal, but also
      liver and peripheral target tissues, significantly contribute to steroid
      alterations in PCOS.

PMID- 12788886
TI  - A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor
      alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype
      in patients with type 2 diabetes.
AB  - Our previous results have suggested that genes outside the human leukocyte
      antigen (HLA) class II locus may affect the phenotype of type 2 diabetic patients
      from families with both type 1 and type 2 diabetes (mixed type 1/2). To study
      whether the TNF alpha gene could be such a modifying gene, we studied TNF alpha
      promoter polymorphisms (G-->A substitution at positions -308 and -238) in
      relation to HLA-DQB1 genotypes in type 2 patients from mixed type 1/2 families or
      common type 2 diabetes families as well as in patients with adult-onset type 1
      diabetes and control subjects. The TNF alpha(308) AA/AG genotype frequency was
      increased in adult onset type 1 patients (55%, 69 of 126), but it was similar in
      type 2 patients from type 1/2 families (35%, 33/93) or common type 2 families
      (31%, 122 of 395), compared with controls (33%, 95/284; P < 0.0001 vs. type 1).
      The TNF alpha(308) A and DQB1*02 alleles were in linkage disequilibrium in type 1
      patients (Ds = 0.81; P < 0.001 vs. Ds = 0.25 in controls) and type 2 patients
      from type 1/2 families (Ds = 0.59, P < 0.05 vs. controls) but not in common type
      2 patients (Ds = 0.39). The polymorphism was associated with an insulin-deficient
      phenotype in the type 2 patients from type 1/2 families only together with
      DQB*02, whereas the common type 2 patients with AA/AG had lower waist to hip
      ratio [0.92 (0.12) vs. 0.94 (0.11), P = 0.008] and lower fasting C-peptide
      concentration [0.48 (0.47) vs. 0.62 (0.46) nmol/liter, P = 0.020] than those with
      GG, independently of the presence of DQB1*02. In conclusion, TNF alpha is
      unlikely to be the second gene in the HLA area responsible for our previous
      findings in type 1/2 patients. However, we could show an association between TNF
      alpha(308) polymorphism and the phenotype of common type 2 diabetes.

PMID- 12788887
TI  - Insulin secretion and cellular glucose metabolism after prolonged low-grade
      intralipid infusion in young men.
AB  - We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on
      peripheral glucose disposal, intracellular glucose partitioning and insulin
      secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp
      [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp (HI), 40 mU/m(2) x
      min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free
      fatty acid concentrations were similar during basal steady state but 3.7- to 13
      fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio
      decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation
      decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and
      glucose production were not significantly altered. At HI, glucose disposal, and
      glucose oxidation decreased by 12% and 24%, respectively, during Intralipid
      infusion. Glycolytic flux, glucose storage, and glucose production were
      unchanged. Insulin secretion rates increased in response to Intralipid infusion,
      but disposition indices (DI = insulin action.insulin secretion) were unchanged.
      In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in
      the oxidative (but not in the nonoxidative) glucose metabolism in young healthy
      men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid
      induced insulin resistance. Future studies are needed to determine the role of a
      prolonged moderate lipid load in subjects at increased risk of developing
      diabetes.

PMID- 12788888
TI  - Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19
      nortestosterone in hypogonadal men.
AB  - The potent synthetic androgen 7 alpha-methyl-19-nortestosterone (MENT) is
      resistant to 5 alpha-reductase but is a substrate for aromatase. It may therefore
      offer selective sparing of the prostate gland while supporting other androgen
      dependent tissues. MENT acetate implants were administered for 24 wk to 16
      hypogonadal men, randomly allocated to 1 or 2 implants (groups I and II,
      respectively; releasing approximately 400 microg/d x implant). Hemoglobin
      concentration and hematocrit were maintained during MENT treatment. Prostate
      volume fell in group I and to a small, but statistically nonsignificant, degree
      in group II; the level of prostate-specific antigen fell significantly in both.
      Lumbar spine bone mineral density decreased in both groups. Sexual behavior and
      erectile function declined in group I, but were maintained in group II. Thus,
      overall, one MENT implant appeared to provide subphysiological androgen
      replacement. The 2-implant dose of MENT was able to maintain most androgen
      dependent functions, except bone mass, and there was evidence to support
      selective sparing of the prostate gland. These results demonstrate for the first
      time in humans the selectivity of MENT in tissues dependent on 5 alpha-reductase.
      In addition, our data are consistent with the importance of adequate
      estrogenicity as part of the necessary spectrum of activity of an androgen for
      replacement therapy in men.

PMID- 12788889
TI  - A rare duplicated 21-hydroxylase haplotype and a de novo mutation: a family
      analysis.
AB  - 21-Hydroxylase (21-OH) genotyping was performed in clinically unaffected family
      members of a congenital adrenal hyperplasia (CAH) index patient (Prader stage 3),
      who is a compound heterozygous carrier of the I172N (exon 4) and the intron2
      splicing mutations. Whereas the latter mutation could be traced to the father,
      the exon 4 aberration represents a de novo mutation (accounting for 1% of CAH
      alleles) harbored on an unaffected allele, which was inherited from the mother.
      Although clinically and biochemically unaffected, the patient's brother was found
      to be compound heterozygous for intron2splice (paternal allele) and Q318X in exon
      8 (maternal allele). As shown by PCR-based sequence and Southern blot analysis,
      the maternal haplotype, inherited by the brother, has a duplicated CYP21B
      (functional) gene, one of which carries a Q318X mutation. This duplicated Q318X
      affected haplotype is the first of its kind among 800 alleles screened for 21-OH
      deficiency in our laboratory and has to date been reported only in three Swedish
      CAH patients, all of them bearing an intron2splice and a Q318X mutation. This
      family analysis highlights the complexity of the CYP21/CYP21P(pseudogene) loci
      and the difficulties of 21-OH genotyping.

PMID- 12788890
TI  - Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)
      and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH,
      and PRL secretion.
AB  - Somatostatin (SRIF) analogs interacting with SRIF receptor subtype (SSTR) 2 and
      SSTR5 are known to reduce secretion in GH-secreting pituitary adenomas. We
      investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH
      and prolactin (PRL) secretion and cell viability in primary cultures deriving
      from 15 GH- and PRL-secreting adenomas expressing SSTR1. Quantitative RT-PCR
      showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/ microg reverse
      transcribed total RNA. SSTR2 and SSTR5 were frequently expressed (93.3%), on the
      contrary of SSTR3 (53.3%) and SSTR4 (6.7%). GH secretion was significantly
      reduced by SRIF and BIM-23926 (45 +/- 8.6% and 32 +/- 18.1% inhibition,
      respectively) as well as PRL secretion (16.1 +/- 4% and 19.7 +/- 3.5% inhibition,
      respectively). After treatment with SRIF and BIM-23926, cell viability was
      significantly reduced by 17.5 +/- 5% and 20 +/- 3.9%, respectively. SSTR1 mRNA
      levels correlated with the degree of GH and PRL secretion inhibition. These
      results demonstrate that SSTR1 selective activation inhibits hormone secretion
      and cell viability in GH- and PRL-secreting adenomas in vitro and suggest that
      SRIF analogs with affinity for SSTR1 may be useful to control hormone
      hypersecretion and reduce neoplastic growth of pituitary adenomas.

PMID- 12788891
TI  - The human kidney is a progesterone-metabolizing and androgen-producing organ.
AB  - Progesterone (P) is a potent antagonist of the human mineralocorticoid receptor
      (MR) in vitro. We have previously demonstrated effective downstream metabolism of
      P in the kidney. This mechanism potentially protects the MR from P action. Here,
      we have investigated the expression and functional activity of steroidogenic
      enzymes in human kidney. RT-PCR analysis demonstrated the expression of 5 alpha
      reductase type 1, 5 beta-reductase, aldo-keto-reductase (AKR) 1C1, AKR1C2,
      AKR1C3, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type 2, and 17 alpha
      hydroxylase/17,20-lyase (P450c17). The presence of 3 beta-HSD type 2 and P450c17
      indicated that conversion of pregnenolone to dehydroepiandrosterone (DHEA) and to
      androstenedione may take place effectively in kidney. To investigate this
      further, we incubated kidney subcellular fractions with radiolabeled
      pregnenolone. This resulted in efficient formation of DHEA from pregnenolone,
      indicating both 17 alpha-hydroxylase and 17,20-lyase activities exerted by
      P450c17. Radiolabeled DHEA was converted via androstenedione, androstenediol, and
      testosterone, indicating both 3 beta-HSD type 2 activity and 17 beta-HSD
      activity. In addition, the conversion of testosterone to 5 alpha
      dihydrotestosterone was detectable, indicating 5 alpha-reductase activity. In
      conclusion, we verified the expression and functional activity of several enzymes
      involved in downstream metabolism of P and androgen synthesis in human kidney.
      These findings may be critical to the understanding of water balance during the
      menstrual cycle and pregnancy and of sex differences in hypertension.

PMID- 12788892
TI  - Prostaglandin E2 regulates aromatase activity and expression in human adipose
      stromal cells via two distinct receptor subtypes.
AB  - The aromatase enzyme complex, located primarily in the stromal cells of breast
      tumors, catalyzes estrogen biosynthesis and is fundamental to hormone-dependent
      growth of breast cancer. Although an important pharmacological target, the
      mechanisms by which aromatase is regulated are poorly understood. Thus,
      regulation of aromatase activity and expression in human breast stromal cells by
      prostaglandin E(2) (PGE(2)) was investigated. PGE(2) exerts its actions via four
      transmembrane receptors, EP(1), EP(2), EP(3), and EP(4), which coordinate
      different signal transduction pathways. Using selective receptor agonists and
      antagonists, the involvement of the EP(1), EP(2), and EP(3) subtypes was
      assessed. Enzyme activity levels in cultures of disease-free stromal cells were
      determined using a tritiated water-release assay. PGE(2) and agonists of EP(1)
      and EP(2) significantly increased aromatase activity levels, which were decreased
      by the corresponding antagonists. An agonist of EP(3), an inhibitory pathway,
      antagonized activity levels induced by PGE(2). These results were generally
      reflective of changes in aromatase protein expression, determined by Western
      blotting analysis and the pattern of mRNA expression determined by a competitive
      RT-PCR method. Collectively, the results demonstrate that regulation of aromatase
      by PGE(2) is complex and may influence the development and progression of hormone
      dependent breast cancer.

PMID- 12788893
TI  - Acute effects of growth hormone on vascular function in human subjects.
AB  - GH is involved in the long-term regulation of peripheral vascular resistance and
      vascular reactivity. We determined whether GH plays a role in the acute
      regulation of vascular function in humans. The acute vascular effects of GH were
      studied in eight healthy subjects according to a double-blind, placebo-controlled
      design. Forearm blood flow (FBF), vascular resistance, and nitric oxide (NO)
      production were monitored during a 4-h infusion of GH into the brachial artery at
      a rate chosen to raise local GH to stress levels (approximately 40 ng/ml). During
      GH infusion, FBF rose 75% (P < 0.05), whereas forearm vascular resistance
      decreased comparably (P < 0.05). These changes were paralleled by augmented
      forearm release of NO (P < 0.02). GH heightened the response of FBF to the
      endothelium-dependent vasodilator acetylcholine (Ach; P < 0.02). With the highest
      Ach dose, FBF reached 30.4 +/- 4.2 and 16.9 +/- 3.1 ml/dl x min in the GH and
      placebo studies, respectively (P < 0.005). The slopes of the dose-response curves
      also differed markedly (0.45 +/- 0.07 and 0.25 +/- 0.05 ml/dl x min/ microg in
      the GH and placebo studies, respectively; P < 0.01). GH caused an upward shift of
      the FBF response to the endothelium-independent vasodilator sodium nitroprusside
      (P < 0.01), but did not affect the slope of the dose-response curve. GH infusion
      did not cause any appreciable increment in the venous IGF-I concentration in the
      test arm. In conclusion, GH acutely lowers peripheral vascular resistance and
      stimulates endothelial function. These effects are mediated by activation of the
      NO pathway and appear to be independent of IGF-I.

PMID- 12788894
TI  - Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia
      associated lipodystrophy.
AB  - Mandibuloacral dysplasia (MAD) is a phenotypically heterogeneous, rare autosomal
      recessive disorder characterized by mandibular and clavicular hypoplasia,
      acroosteolysis, delayed closure of cranial sutures, joint contractures, and
      mottled cutaneous pigmentation. Patients with MAD develop two patterns of
      lipodystrophy: type A pattern, with loss of sc fat from the extremities and
      normal or slight excess in the neck and truncal regions; and type B pattern, with
      a more generalized loss of sc fat involving the face, trunk, and extremities.
      Recently, affected patients from five consanguineous Italian pedigrees with
      partial lipodystrophy (type A) were reported to have a homozygous R527H mutation
      in LMNA (lamin A/C) gene. We carried out mutational analysis of LMNA in affected
      patients from six pedigrees. Affected patients from two pedigrees with type A
      lipodystrophy had the homozygous R527H mutation in LMNA. The other four affected
      subjects who had type B lipodystrophy did not have any mutation in the exons and
      splice site junctions of LMNA; RNA extracted from lymphoblasts of two of these
      patients also revealed normal sequence. In these four subjects, sequencing of
      other known genes implicated in lipodystrophies, i.e. AGPAT2, Seipin, and PPARG
      also revealed no substantial alterations. We conclude that MAD is a genetically
      and phenotypically heterogeneous disorder. Besides LMNA gene, other as yet
      unmapped loci could be linked to MAD.

PMID- 12788895
TI  - Role for inner ring deiodination preventing transcutaneous passage of thyroxine.
AB  - Creams containing thyroid hormone are commonly employed for cosmetic purposes. To
      verify whether T(4) applied to the skin surface can enter the bloodstream either
      directly or as a metabolite, a cream containing L-T(4) [3,5,3',5'
      tetraiodothyronine (T(4))] was self-applied by volunteers for 2 wk. No
      significant variations in urinary iodide, TSH, and serum (total and free) T(4)
      and T(3) concentrations were observed at any time relative to pretreatment
      values, whereas rT(3) concentrations increased significantly 6 and 12 h after
      cream application. The increased rT(3) concentration led us to investigate the
      presence of inner ring type III deiodinase (D3) activity in human skin. Using
      human surgical discard skin, we found that T(4) can be carried across human
      epidermis in a liposome cream. Substantial inner ring deiodination was suggested
      by the fact that only 10% of transferred thyroid hormone remained as T(4), and
      T(3) was not detected. We then measured D3 activity in a surgical skin specimen.
      The K(m) for T(3) was 1.74 nmol/liter, and the maximum velocity was 23.5
      fmol/microg microsomal protein/h. In conclusion, our study indicates that normal
      human skin serves as a substantial, but incomplete, barrier to T(4) passage. D3
      plays an important role in augmenting T(4) blockade by inactivating T(4) to
      rT(3).

PMID- 12788896
TI  - Activity and protein expression of Na+/K+ ATPase are reduced in microvillous
      syncytiotrophoblast plasma membranes isolated from pregnancies complicated by
      intrauterine growth restriction.
AB  - In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is
      distributed to both the microvillous membrane (MVM) and the basal membrane (BM)
      of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in
      maintaining the electrochemical gradient for Na(+), which represents the driving
      force for Na(+)-coupled transport of nutrients. We hypothesized that
      syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth
      restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR
      placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit
      was determined by Western blotting and found to be slightly reduced in MVM
      isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was
      measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent
      pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM
      obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of
      Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady
      state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the
      Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were
      unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity
      is reduced in the MVM of placentas from IUGR pregnancies. These changes might
      impair the function of Na(+)-coupled transporters and contribute to the reduced
      growth of these fetuses.

PMID- 12788897
TI  - Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison
      with leptin, circulating soluble leptin receptor, and cortisol patterns.
AB  - Adiponectin is an abundant serum adipokine secreted exclusively from
      differentiated adipocytes, which plays an important role in regulating insulin
      sensitivity. The dynamics of circulating adiponectin concentrations have yet to
      be systematically investigated. We sought to determine whether serum adiponectin
      levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to
      compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin
      binding protein (sOB-R), and cortisol. We collected blood samples at 15-min
      intervals over 24 h from six subjects receiving an isocaloric diet, and we
      measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross
      correlation analyses were performed on these time series to study diurnal
      variations, and the Cluster7 program was used for pulsatility analysis.
      Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well
      as a diurnal variation with a significant decline at night, reaching a nadir in
      the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly
      identical and followed those of cortisol after a few hours, but were out-of-phase
      with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels
      might be influenced by common regulatory factors and challenge the notion that
      cortisol may have a direct inhibitory effect on adiponectin in humans.

PMID- 12788898
TI  - Acute temporal regulation of vascular endothelial growth/permeability factor
      expression and endothelial morphology in the baboon endometrium by ovarian
      steroids.
AB  - We recently showed that endometrial vascular endothelial growth/permeability
      factor (VEG/PF) mRNA expression was decreased by ovariectomy of baboons and
      restored by chronic administration of estrogen. However, it remains to be
      determined whether this effect of estrogen reflects genomic up-regulation of
      VEG/PF and leads to an increase in microvascular permeability, an early
      physiological event in angiogenesis. Therefore, we determined the temporal
      expression of VEG/PF mRNA in glandular epithelial and stromal cells isolated by
      laser capture microdissection from and width of microvascular paracellular clefts
      that regulate vessel permeability in the endometrium of ovariectomized baboons
      after acute estradiol and/or progesterone administration. Endometrial VEG/PF mRNA
      levels were increased in five of five animals within 2 h of estradiol
      administration and remained elevated at 4 and 6 h. The net increase in glandular
      epithelial (7.31 +/- 2.72 attomol/fmol 18S ribosomal rRNA) and stromal (3.13 +/-
      0.36) cell VEG/PF mRNA levels after estradiol administration was over 8-fold (P <
      0.05) and 2.6-fold (P < 0.01) greater, respectively, than after vehicle (0.90 +/-
      0.30, glands and 1.20 +/- 0.33, stroma). In contrast, endometrial VEG/PF mRNA
      expression was unaltered by progesterone. After estradiol treatment, endometrial
      paracellular cleft width was increased (P < 0.01) from a mean (+/-SE) of 71.6 +/-
      4.6 nm at 0 h to 101.1 +/- 6.4 nm at 6 h, whereas vehicle or progesterone had no
      effect. We suggest that estrogen has a major role in regulating VEG/PF synthesis
      and early events in angiogenesis in the primate endometrium.

PMID- 12788899
TI  - Different basic fibroblast growth factor and fibroblast growth factor-antisense
      expression in eutopic endometrial stromal cells derived from women with and
      without endometriosis.
AB  - In all species studied, the basic fibroblast growth factor (bFGF) gene is
      transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS)
      probably involved in regulating the stability of the sense transcript. In this
      study we investigated whether the regulatory mechanisms of bFGF expression might
      be altered in endometrial stromal cells derived from women with endometriosis.
      bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic
      endometrial stromal cells derived from 29 women without endometriosis and 24
      patients affected by the disease. When the data were analyzed according to the
      phase of the menstrual cycle, endometrial stromal cells derived from patients in
      the late proliferative phase showed significantly higher bFGF mRNA values and
      significantly lower 1B FGF-AS mRNA levels compared with control samples.
      Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in
      endometrial stromal cells derived from patients compared with that in controls
      (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009).
      Moreover, for bFGF expression the differences existing at the mRNA level were
      maintained at the protein level. These findings support the hypothesis that 1B
      FGF-AS mRNA could regulate the expression of the sense transcript and suggest
      that in endometrial cells derived from patients, the presence of higher bFGF
      levels could improve their ability to proliferate at the ectopic site.

PMID- 12788900
TI  - Effects of growth hormone replacement on parathyroid hormone sensitivity and bone
      mineral metabolism.
AB  - Adult GH deficiency (AGHD) is associated with reduced bone mineral density, and
      decreased end-organ sensitivity to the effects of PTH has been suggested as a
      possible underlying mechanism. We investigated the effects of GH replacement
      (GHR) on PTH circulating activity and its association with phosphocalcium
      metabolism and bone turnover in 16 (8 men and 8 women) AGHD patients. Half-hourly
      blood and 3 hourly urine sampling was performed on each patient over a 24-h
      period before GHR and then after 1, 3, 6, and 12 months of GHR. GH was commenced
      at a dose of 0.5 IU/d and was titrated to achieve and maintain an IGF-I SD score
      within 2 SD of the age-related reference range. The target IGF-I SD score was
      achieved within 3 months and was maintained at 12 months after GHR in all
      patients. Our results demonstrated a significant decrease in serum PTH at all
      visits after GHR compared with baseline values (P < 0.001), with a concomitant
      increase in nephrogenous cAMP excretion at 1 (P < 0.001) and 3 (P < 0.05) months
      and increases in serum calcium (P < 0.001), serum phosphate (P < 0.001), 1,25
      dihydroxyvitamin D(3) (P < 0.001), type I collagen C-telopeptide (a bone
      resorption marker; P < 0.001), and procollagen type I amino-terminal propeptide
      (a bone formation marker; P < 0.001). Simultaneously, we observed a significant
      decrease in urinary calcium excretion (P < 0.001) and an increase in maximum
      tubular phosphate reabsorption (P < 0.001). Together these results suggest
      increased end-organ responsiveness to the effects of circulating PTH resulting in
      increased bone turnover and reduced calcium excretion. Significant circadian
      rhythms were observed for serum PTH, phosphate, type I collagen C-telopeptide,
      and procollagen type I amino-terminal propeptide before and after GHR. However,
      sustained PTH secretion was observed between 1400-2200 h, with a reduced
      nocturnal rise in untreated AGHD patients, whereas PTH secretion decreased
      significantly between 1400-2200 h (P < 0.001), with a significant increase in
      nocturnal PTH secretion (P < 0.001) after 12 months of GHR. Our results
      demonstrate that GH may have a regulatory role in bone mineral metabolism, and
      our data provide a possible underlying mechanism for the development of
      osteoporosis in AGHD patients. The changes observed after GHR may further explain
      the beneficial effects of GHR on bone mineral density that have consistently been
      reported.

PMID- 12788902
TI  - Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and
      iodothyronine levels in healthy subjects.
AB  - Single nucleotide polymorphisms (SNPs) in genes involved in thyroid hormone
      metabolism may affect thyroid hormone bioactivity. We investigated the occurrence
      and possible effects of SNPs in the deiodinases (D1-D3), the TSH receptor (TSHR),
      and the T(3) receptor beta (TR beta) genes. SNPs were identified in public
      databases or by sequencing of genomic DNA from 15 randomly selected subjects (30
      alleles). Genotypes for the identified SNPs were determined in 156 healthy blood
      donors and related to plasma T(4), free T(4), T(3), rT(3), and TSH levels. Eight
      SNPs of interest were identified, four of which had not yet been published. Three
      are located in the 3'-untranslated region: D1a-C/T (allele frequencies, C = 66%,
      T = 34%), D1b-A/G (A = 89.7%, G = 10.3%), and D3-T/G (T = 85.5%, G = 14.2%). Four
      are missense SNPs: D2-A/G (Thr92Ala, Thr = 61.2%, Ala = 38.8%), TSHRa-G/C
      (Asp36His, Asp = 99.4%, His = 0.6%), TSHRb-C/A (Pro52Thr, Pro = 94.2%, Thr =
      5.8%), and TSHRc-C/G (Asp727Glu, Asp = 90.7%, Glu = 9.3%). One is a silent SNP:
      TR beta-T/C (T = 96.8%, C = 3.2%). D1a-T was associated in a dose-dependent
      manner with a higher plasma rT(3) [CC, 0.29 +/- 0.01; CT, 0.32 +/- 0.01; and TT,
      0.34 +/- 0.02 nmol/liter (mean +/- SE); P = 0.017], a higher plasma rT(3)/T(4) (P
      = 0.01), and a lower T(3)/rT(3) (P = 0.003) ratio. The D1b-G allele was
      associated with lower plasma rT(3)/T(4) (P = 0.024) and with higher T(3)/rT(3) (P
      = 0.08) ratios. TSHRc-G was associated with a lower plasma TSH (CC, 1.38 +/-
      0.07, vs. GC, 1.06 +/- 0.14 mU/liter; P = 0.04), and with lower plasma TSH/free
      T(4) (P = 0.06), TSH/T(3) (P = 0.06), and TSH/T(4) (P = 0.08) ratios. No
      associations with TSH and iodothyronine levels were found for the other SNPs. We
      have analyzed eight SNPs in five thyroid hormone pathway genes and found
      significant associations of three SNPs in two genes (D1, TSHR) with plasma TSH or
      iodothyronine levels in a normal population.

PMID- 12788901
TI  - Genetic variation at the scavenger receptor class B type I gene locus determines
      plasma lipoprotein concentrations and particle size and interacts with type 2
      diabetes: the framingham study.
AB  - The scavenger receptor class B type I (SR-BI) is a key component in the reverse
      cholesterol transport pathway. We have previously reported three common
      polymorphisms associated with plasma lipids and body mass index. We hypothesized
      that diabetic status may interact with these polymorphisms in determining plasma
      lipid concentrations and particle size. We evaluated this hypothesis in 2463
      nondiabetic (49% men) and 187 diabetic (64% men) participants in the Framingham
      Study. SR-BI and APOE genotypes, anthropometric, clinical, biochemical, and
      lifestyle variables were determined. After multivariate adjustment, we found a
      consistent association between the exon 8 polymorphism and high-density
      lipoprotein cholesterol concentration and particle size. Interaction effects were
      not significant for exon 8 and intron 5 polymorphisms. However, we found
      statistically significant interactions between SR-BI exon 1 genotypes and type 2
      diabetes, indicating that diabetic subjects with the less common allele (allele
      A) have lower lipid concentrations. For low-density lipoprotein cholesterol, the
      adjusted means (+/-SE) were 3.31 +/- 0.03 and 3.29 +/- 0.04 mmol/liter for G/G
      and G/A or A/A in nondiabetics, respectively, compared with 3.19 +/- 0.10 and
      2.75 +/- 0.01 mmol/liter for G/G and G/A or A/A in diabetics (P = 0.03 for
      interaction). Similar results were obtained for HDL(2)-C. In conclusion, SR-BI
      gene variation modulates the lipid profile, particularly in type 2 diabetes,
      contributing to the metabolic abnormalities in these subjects.

PMID- 12788903
TI  - Antiangiogenic agents are effective inhibitors of endometriosis.
AB  - Endometriosis is a disease in which the lining of the uterus (endometrium), shed
      at the time of menstruation, becomes established at sites such as the peritoneum
      and ovaries. These explants develop a rich blood supply that enables them to
      survive and grow. We hypothesized that inhibitors of angiogenesis would prevent
      this growth by disrupting sensitive vessels supplying endometriotic lesions.
      Vessels sensitive to angiogenic antagonism have few associations with pericyte
      cells. The vessels supplying human endometriotic lesions were
      immunohistochemically characterized and found to be predominantly pericyte free.
      A model in which human endometrium is implanted into nude mice was used to test
      the effects of two antagonists of the angiogenic growth factor, vascular
      endothelial cell growth factor A. Soluble truncated receptor (flt-1; P = 0.002)
      and an affinity-purified antibody to human vascular endothelial cell growth
      factor A (P = 0.03) significantly inhibited the growth of nude mouse explants.
      Pericyte-free vessels were shown to supply endometrial lesions in nude mice and
      were disrupted in lesions taken from soluble flt-1-treated mice. In summary,
      antiangiogenic agents inhibited the growth of explants in an in vivo model of
      endometriosis by disrupting the vascular supply, and this effect is likely to
      apply to the human disease. These findings suggest that antiangiogenic agents may
      provide a novel therapeutic approach for the treatment of endometriosis.

PMID- 12788904
TI  - Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase
      mediated induction of apoptosis.
AB  - Bovine seminal ribonuclease (BS-RNase), a natural dimeric homolog of bovine
      pancreatic RNase (RNase A), and HHP2-RNase, an engineered dimeric form of human
      pancreatic RNase (HP-RNase), are endowed with powerful antitumor effects. Here we
      show that BS- and HHP2-RNases, but not monomeric RNase A, induce apoptosis of
      human thyroid carcinoma cell lines. RNase-induced apoptosis was associated with
      activation of initiation caspase-8 and -9. This was followed by activation of
      executioner caspase-3, leading to the proteolytic cleavage of poly(ADP-ribose)
      polymerase. The caspase inhibitor Z-Val-Ala-Asp-(OMe)-fluoromethylketone
      protected thyroid cancer cells from BS-RNase-induced apoptosis. RNase-triggered
      apoptosis and caspase activation were accompanied by reduced phosphorylation of
      Akt/protein kinase B (PKB), a serine-threonine kinase that when phosphorylated is
      able to deliver survival signals to cancer cells. BS-RNase antitumor effects in
      nude mice were accompanied by caspase activation and apoptosis. Because of the
      high selectivity of apoptotic effects for malignant cells, BS- and HHP2-RNase are
      promising tools for the treatment of aggressive thyroid cancer.

PMID- 12788905
TI  - Endocrine and metabolic responses to long-term monotherapy with the antiepileptic
      drug valproate in the normally cycling rhesus monkey.
AB  - An association between epilepsy and reproductive disturbances with an apparent
      increase in a polycystic ovarian syndrome (PCOS) has been reported. Whether this
      association can be attributed to epilepsy itself or is related to antiepileptic
      drug therapy, in particular valproate (VPA), remains controversial. We studied
      effects of a long-term VPA treatment on cycling monkeys, postulating that, if VPA
      monotherapy were to promote abnormal endocrine and metabolic parameters that are
      characteristic of PCOS, changes in cyclicity would be readily demonstrated. After
      a 2-month control, a 12- to 15-month VPA monotherapy was initiated in 7 regularly
      cycling rhesus monkeys. Overall mean levels of VPA were 88.7 +/- 4.0 (SE)
      microg/ml. Mean body weight increased progressively during VPA treatment from 8.5
      +/- 0.5 kg before treatment to 9.6 +/- 0.7 kg in the last week of treatment (P <
      0.05). Monkeys continued to have regular ovulatory menstrual cycles throughout
      VPA monotherapy. Length of the cycles was 28 +/- 0.58 d in control and 28.4 +/-
      1.18 d in the last 3 months of VPA treatment. Follicular and luteal lengths and
      peak preovulatory estradiol and integrated luteal progesterone levels did not
      differ between control and treatment. Ovaries from VPA-treated monkeys showed
      histological evidence of ovulation, and none had characteristic features of PCOS.
      Endocrine PCOS markers, such as increased early follicular LH/FSH ratio and
      androgen levels were not different in control and VPA treatment cycles. LH and 17
      hydroxyprogesterone responses to GnRH agonist challenges and the insulin response
      to glucose tolerance tests were similar in control and VPA groups. Lipid profiles
      were not affected by VPA treatment. The data indicate that a 12- to 15-month
      therapeutic exposure to VPA does not induce cyclic hormonal or morphological
      ovarian abnormalities or characteristics of the PCOS when administered to
      nonepileptic normally cycling nonhuman primates.

PMID- 12788906
TI  - Mutations in the PDS gene in German families with Pendred's syndrome: V138F is a
      founder mutation.
AB  - Pendred's syndrome, an autosomal-recessive condition characterized by congenital
      sensorineural hearing loss and goiter, is caused by mutations in the PDS gene.
      Located on chromosome 7q22-q31, it encodes a chloride-iodide transporter
      expressed in the thyroid, inner ear, and kidney. We investigated the PDS gene of
      six affected individuals from four unrelated families with Pendred's syndrome by
      direct sequencing. PDS mutations were identified in homozygous or compound
      heterozygous state in all six cases. A homozygous missense mutation leading to
      the amino acid substitution S133T was detected in a family of Turkish origin. The
      mutations found in the other affected individuals, who originate from Germany,
      were V138F/Y530H, V138F/E384G, and V138F/V138F. Because V138F was found in the
      German patients with Pendred's syndrome on at least one allele, we genotyped five
      microsatellite markers located in the PDS region. All affected German individuals
      shared a common haplotype at three microsatellite markers located close to or
      within the PDS gene. We therefore concluded that V138F is a founder mutation in
      our cohort of German families with Pendred's syndrome.

PMID- 12788908
TI  - Developmental changes in the hormonal identity of gonadotroph cells in the rhesus
      monkey pituitary gland.
AB  - To help elucidate the regulatory mechanism responsible for divergent
      gonadotrophin secretion during sexual maturation, we examined the gonadotroph
      population and hormonal identity of gonadotroph subtypes in pituitary glands of
      juvenile (age, 1.7 +/- 0.2 yr) and adult (age, 12.3 +/- 0.8 yr) male rhesus
      monkeys (Macacca mulatta). Serum LH and testosterone concentrations were,
      respectively, 3 and 7 times lower in juveniles than in adults, thus confirming
      the different stages of development. Immunohistochemistry revealed that the
      proportion of LH gonadotrophs in relation to the total pituitary cell population
      in the juvenile animals was significantly smaller than in the adults. In a
      subsequent study, double immunofluorescent labeling identified three distinct
      gonadotroph subtypes in both age groups: ones expressing either LH or FSH and
      another one expressing a combination of both gonadotrophins. Whereas the number
      of monohormonal LH cells per unit area was greater in the adults than in the
      juveniles, the number of monohormonal FSH gonadotrophs was remarkably lower.
      However, the proportion of FSH cells (whether mono- or bihormonal) within the
      gonadotroph population was similar between groups. Interestingly, the proportion
      and number of bihormonal gonadotrophs as well as the LH/FSH gonadotroph ratio
      were significantly greater in the adults than in the juveniles. Taken together,
      these data reveal that during the juvenile-adult transition period, not only does
      the pituitary gonadotroph population increase, but a large number of monohormonal
      FSH gonadotrophs are likely to become bihormonal. Because this morphological
      switch occurs when marked changes in plasma gonadotrophins are known to occur, it
      may represent an intrapituitary mechanism that differentially regulates
      gonadotrophin secretion during sexual development.

PMID- 12788907
TI  - Mechanism of cortisol/progesterone antagonism in the regulation of 15
      hydroxyprostaglandin dehydrogenase activity and messenger ribonucleic acid levels
      in human chorion and placental trophoblast cells at term.
AB  - Prostaglandin dehydrogenase (PGDH) metabolizes prostaglandins (PGs) to render
      them inactive. We reported previously that cortisol (F) decreases and
      progesterone (P(4)) maintains PGDH activity/expression in human chorion and
      placenta. Furthermore, we have shown that F and P(4) compete for regulation of
      PGDH. We hypothesized that P(4) maintains PGDH activity through interaction with
      the glucocorticoid receptor (GR) and that elevations in F compete with P(4) at
      the GR, resulting in a decrease in PGDH at term. By immunohistochemistry and
      Western blotting analysis, we localized immunoreactive GR and progesterone
      receptor (PR) to chorion and placental trophoblast cells. We treated chorion and
      placental trophoblast cells in culture with F, dexamethasone (DEX), beta
      methasone, P(4), trilostane (a 3 beta-hydroxysteroid dehydrogenase inhibitor),
      medroxyprogesterone acetate (MPA), and/or 21-hydroxy-6,19-oxidopregn-4-ene-3,20
      dione (21OH-6OP; a GR antagonist). By RIA and Northern blotting analysis, all
      glucocorticoids (GCs) decreased PGDH activity/expression. Coincubation with 21OH
      6OP reversed GC inhibition of PGDH; MPA, but not P(4), treatment stimulated PGDH
      activity. Trilostane inhibited PGDH activity, and coincubation with P(4) or MPA
      reversed trilostane inhibition of PGDH. Treatment with trilostane, P(4), 21OH
      6OP, or MPA plus 21OH-6OP reversed P(4) and MPA up-regulation of PGDH activity.
      Our findings suggest that F inhibition and P(4) stimulation of PGDH may be
      mediated by PR, but also via the GR, in chorion and placenta.

PMID- 12788909
TI  - Cerebrospinal fluid ghrelin is negatively associated with body mass index.
AB  - Ghrelin is a 28 amino acid peptide hormone, predominantly expressed in the
      gastric epithelium and, at a lower level, in the hypothalamus. Although several
      lines of evidence indicate that ghrelin has a role in appetite regulation,
      nevertheless the regulation and role of central ghrelin levels remain unclear. To
      further characterize the role of ghrelin in the regulation of body adiposity, we
      investigated the association between fasting cerebrospinal fluid (CSF) ghrelin
      levels and body mass index (BMI) in humans. We consecutively enrolled 19 adults
      (aged 21-76 yr, 15 females and 4 males), including 4 obese, 7 overweight and 8
      lean subjects, who underwent spinal anesthesia during surgery for non-malignant
      conditions. We found a negative association between fasting CSF ghrelin levels
      and BMI (r = -0.48, p = 0.035) and a trend towards lower (by 16%) fasting CSF
      ghrelin levels in the obese (p = 0.06 for the difference between lean and obese
      subjects). In conclusion, we found a negative association between fasting CSF
      ghrelin levels and BMI in humans. Our data suggest that central ghrelin may have
      a role in the regulation of body adiposity in humans, which requires further
      study to be fully elucidated.

PMID- 12788910
TI  - A locus for autosomal recessive idiopathic hypogonadotropic hypogonadism on
      chromosome 19p13.3.
AB  - Idiopathic hypogonadotropic hypogonadism (IHH) is traditionally established by 1)
      the absence of spontaneous pubertal development by age 18 yr and 2) low sex
      steroids with inappropriately low gonadotropins in the absence of any functional
      or anatomic cause. To identify a novel disease locus for IHH, a genome wide scan
      was performed on a large, consanguineous Saudi family with 6 affected
      individuals. Linkage over a 1.06 Mb interval on chromosome 19p13.3 was
      established with a maximal two point LOD score of 5.17. Because numerous genes
      and hypothetical proteins are mapped to this region, further studies will be
      necessary to determine the precise genetic defect in this family.

PMID- 12788912
TI  - Cortisol metabolism and glucose intolerance.

PMID- 12788913
TI  - Reversal of the deoxyhypusine synthesis reaction. Generation of spermidine or
      homospermidine from deoxyhypusine by deoxyhypusine synthase.
AB  - Deoxyhypusine synthase catalyzes the first step in hypusine (N epsilon-(4-amino-2
      hydroxybutyl)lysine) synthesis in a single cellular protein, eIF5A precursor. The
      synthesis of deoxyhypusine catalyzed by this enzyme involves transfer of the 4
      aminobutyl moiety of spermidine to a specific lysine residue in the eIF5A
      precursor protein to form a deoxyhypusine-containing eIF5A intermediate,
      eIF5A(Dhp). We recently discovered the efficient reversal of deoxyhypusine
      synthesis. When eIF5A([3H]Dhp), radiolabeled in the 4-aminobutyl portion of its
      deoxyhypusine residue, was incubated with human deoxyhypusine synthase, NAD, and
      1,3-diaminopropane, [3H]spermidine was formed by a rapid transfer of the
      radiolabeled 4-aminobutyl side chain of the [3H]deoxyhypusine residue to 1,3
      diaminopropane. No reversal was observed with [3H]hypusine protein, suggesting
      that hydroxylation at the 4-aminobutyl side chain of the deoxyhypusine residue
      prevents deoxyhypusine synthase-mediated reversal of the modification. Purified
      human deoxyhypusine synthase also exhibited homospermidine synthesis activity
      when incubated with spermidine, NAD, and putrescine. Thus it was found that
      [14C]putrescine can replace eIF5A precursor protein as an acceptor of the 4
      aminobutyl moiety of spermidine to form radiolabeled homospermidine. The Km value
      for putrescine (1.12 mM) as a 4-aminobutyl acceptor, however, is much higher than
      that for eIF5A precursor (1.5 microM). Using [14C]putrescine as an acceptor,
      various spermidine analogs were evaluated as donor substrates for human
      deoxyhypusine synthase. Comparison of spermidine analogs as inhibitors of
      deoxyhypusine synthesis, as donor substrates for synthesis of deoxyhypusine (or
      its analog), and for synthesis of homospermidine (or its analog) provides new
      insights into the intricate specificity of this enzyme and versatility of the
      deoxyhypusine synthase reaction.

PMID- 12788914
TI  - Functional interactions between Hsp90 and the co-chaperones Cns1 and Cpr7 in
      Saccharomyces cerevisiae.
AB  - Hsp90 complexes contain a class of co-chaperones characterized by a
      tetratricopeptide repeat (TPR) domain, which mediates binding to a carboxyl
      terminal EEVD region in Hsp90. Among Hsp90 TPR co-chaperones in Saccharomyces
      cerevisiae, only Cns1 is essential. The amino terminus of Cns1, which harbors the
      TPR domain, is sufficient for viability when overexpressed. In a screen for
      temperature-sensitive alleles of CNS1, we identified mutations resulting in
      substitutions of conserved residues in the TPR domain. Mutations in CNS1 disrupt
      in vitro and in vivo interaction with Hsp90 and reduce Hsp90 function, indicating
      that Cns1 is a bona fide co-chaperone. Genetic interactions between CNS1 and
      another Hsp90 co-chaperone, CPR7, suggest that the two co-chaperones share an
      essential role in the cell. Although both the TPR and the isomerase domains of
      the cyclophilin Cpr7 are required for viability of cns1 mutant cells, this
      requirement does not depend on the catalytic function of the isomerase domain.
      Instead, hydrophilic residues on the surface of this domain appear to be
      important for the common Cns1.Cpr7 function. Although both co-chaperones interact
      with Hsp90 primarily through the carboxyl terminus (EEVD), Cns1 and Cpr7 are
      mostly found in complexes distinct from Hsp90. EEVD is required for normal growth
      in cns1 mutant cells, demonstrating for the first time in vivo requirement for
      this conserved region of Hsp90. Overall, our findings reveal a considerable
      degree of complexity in the interactions not only between Hsp90 and its co
      chaperones, but also among the co-chaperones themselves.

PMID- 12788915
TI  - Characterization of p53-mediated up-regulation of CD95 gene expression upon
      genotoxic treatment in human breast tumor cells.
AB  - Death receptor CD95 gene expression is frequently low in human breast tumors and
      is up-regulated by genotoxic treatments in a p53-dependent manner. We have
      evaluated the relative contribution of promoter and intronic p53 consensus sites
      to the regulation of the human CD95 gene in breast tumor cells following
      doxorubicin treatment. Deletion constructs of the promoter region and site
      directed mutagenesis of p53 consensus sites in a fragment spanning 1448 bp of the
      5'-promoter demonstrate that these sites are not involved in the observed up
      regulation of the CD95 gene upon doxorubicin treatment. In contrast, a p53
      consensus site located within the first intron of CD95 gene is absolutely
      required for the inducible expression of CD95 upon genotoxic treatment in breast
      tumor cells. Analysis of the transcriptional activity of the two most common p53
      mutants found in human breast tumors that are associated with resistance to
      doxorubicin reveals that these mutations completely eliminate the ability of p53
      protein to transactivate CD95 gene expression. On the other hand, Bcl-2
      overexpression albeit preventing doxorubicin-induced apoptosis, has no effect on
      p53-mediated CD95 up-regulation in breast tumor cells. Altogether, these results
      indicate the lack of involvement of p53 consensus sites of the CD95 promoter
      region and the pivotal role of intronic p53-responsive element in the regulation
      of human CD95 gene expression in breast tumor cells. Our results also suggest
      that in breast cancer patients with certain mutations in the p53 gene, expression
      of death receptor CD95 in response to genotoxic treatments could be severely
      compromised.

PMID- 12788916
TI  - Unbound form of tomato inhibitor-II reveals interdomain flexibility and
      conformational variability in the reactive site loops.
AB  - The Potato II (Pot II) family of proteinase inhibitors plays important roles in
      the constitutive and inducible defense of plants against predation by a wide
      range of pests. The structural basis of inhibition by a multidomain Pot II family
      inhibitor was revealed recently by the structure of the ternary complex between
      the two-headed tomato inhibitor-II (TI-II) and two molecules of subtilisin
      Carlsberg. Here we report the 2.15-A resolution crystal structure of the unbound
      form of TI-II that reveals significant conformational flexibility in the absence
      of bound proteinase molecules. The four independent copies of unbound TI-II in
      the asymmetric unit of the unit cell display a range of different conformations
      when compared with the bound form of the inhibitor, most strikingly in the
      orientations of the inhibitory domains and in the conformations of the reactive
      site loops. One of the two linker segments (residues 74 to 79) between the two
      domains as well as the adjacent beta-strand in Domain I (residues 80-85) is well
      ordered in all four copies of the unbound inhibitor, even though this region
      appeared to be disordered in the structure of the ternary complex. Conformational
      flexibility seen in the reactive site loops of unbound TI-II suggests a mechanism
      by which the inhibitor can balance the need for tight binding with the need for
      broad inhibitory function.

PMID- 12788917
TI  - Type XIX collagen purified from human umbilical cord is characterized by multiple
      sharp kinks delineating collagenous subdomains and by intermolecular aggregates
      via globular, disulfide-linked, and heparin-binding amino termini.
AB  - Type XIX collagen was discovered from the sequence of rhabdomyosarcoma cDNA
      clones. The chain is composed of a 268-residue amino terminus, an 832-residue
      discontinuous collagenous region, and a 19-residue carboxyl peptide. Light
      microscopy immunohistochemistry of adult human tissues demonstrated that type XIX
      is localized in vascular, neuronal, mesenchymal, and some epithelial basement
      membrane zones. It also appears to be involved in events linked to skeletal
      myogenesis. In this report, we have presented the first direct evidence for the
      molecular structure of type XIX collagen. Using human umbilical cord, native type
      XIX was purified by neutral salt extraction and by ion exchange and antibody
      affinity chromatography. Type XIX was found to represent only approximately 10(
      6)% of the dry weight of tissue, making it by far the least abundant collagen
      ever isolated. Transmission electron microscopy after rotary shadowing revealed
      the appearance of rodlike structures with multiple sharp bends, a small nodule at
      one end of the molecule, and a total length of 240 nm. Domain-specific antibodies
      were used to identify the nodule as the noncollagenous amino terminus, whereas
      the location of most kinks corresponds to major interruptions separating the five
      collagenous subdomains. More than half of the type XIX molecules observed were
      present in oligomers of different size and complexity, resulting from association
      of the amino-terminal domains. Biochemical analysis demonstrated that these
      supramolecular aggregates are dependent upon and/or stabilized by intermolecular
      disulfide cross-links and that the globular amino terminus contains a high
      affinity, heparin-binding site. The polymorphic conformational states of this
      rare collagen, and its ability to self-assemble into a higher order structure
      provide focal points for future determination of biologically significant
      functions in cell-cell and/or cell-matrix interactions.

PMID- 12788918
TI  - Age-related changes in the biomolecular mechanisms of calvarial osteoblast
      biology affect fibroblast growth factor-2 signaling and osteogenesis.
AB  - The ability of immature animals to orchestrate successful calvarial ossification
      has been well described. This capacity is markedly attenuated in mature animals
      and humans greater than 2 years of age. Few studies have investigated biological
      differences between juvenile and adult osteoblasts that mediate successful
      osteogenesis. To identify possible mechanisms for this clinical observation, we
      investigated cellular and molecular differences between primary osteoblasts
      derived from juvenile (2-day-old) and adult (60-day-old) rat calvaria. Data
      demonstrated that juvenile osteoblasts contain a subpopulation of less
      differentiated cells as observed by spindle-like morphology and decreased
      osteocalcin production. Juvenile, compared with adult, osteoblasts showed
      increased proliferation and adhesion. Furthermore, following rhFGF-2 stimulation
      juvenile osteoblasts increased expression of collagen I alpha 1 (5-fold),
      osteopontin (13-fold), and osteocalcin (16-fold), compared with relatively
      unchanged adult osteoblasts. Additionally, juvenile osteoblasts organized and
      produced more matrix proteins and formed 41-fold more bone nodules.
      Alternatively, adult osteoblasts produced more FGF-2 and preferentially
      translated the high molecular weight (22 kDa) form. Although adult osteoblasts
      transcribed more FGF-R1 and juvenile osteoblasts transcribed more FGF-R2 at
      baseline levels, juvenile osteoblasts translated more FGF-R1 and -R2 and showed
      increased phosphorylation. Collectively, these findings begin to explain why
      juvenile, but not adult, osteoblasts successfully heal calvarial defects.

PMID- 12788919
TI  - Genome-based identification and analysis of collagen-related structural motifs in
      bacterial and viral proteins.
AB  - Collagens are extended trimeric proteins composed of the repetitive sequence
      glycine-X-Y. A collagen-related structural motif (CSM) containing glycine-X-Y
      repeats is also found in numerous proteins often referred to as collagen-like
      proteins. Little is known about CSMs in bacteria and viruses, but the occurrence
      of such motifs has recently been demonstrated. Moreover, bacterial CSMs form
      collagen-like trimers, even though these organisms cannot synthesize
      hydroxyproline, a critical residue for the stability of the collagen triple
      helix. Here we present 100 novel proteins of bacteria and viruses (including
      bacteriophages) containing CSMs identified by in silico analyses of genomic
      sequences. These CSMs differ significantly from human collagens in amino acid
      content and distribution; bacterial and viral CSMs have a lower proline content
      and a preference for proline in the X position of GXY triplets. Moreover, the
      CSMs identified contained more threonine than collagens, and in 17 of 53
      bacterial CSMs threonine was the dominating amino acid in the Y position.
      Molecular modeling suggests that threonines in the Y position make direct
      hydrogen bonds to neighboring backbone carbonyls and thus substitute for
      hydroxyproline in the stabilization of the collagen-like triple-helix of
      bacterial CSMs. The majority of the remaining CSMs were either rich in proline or
      rich in charged residues. The bacterial proteins containing a CSM that could be
      functionally annotated were either surface structures or spore components,
      whereas the viral proteins generally could be annotated as structural components
      of the viral particle. The limited occurrence of CSMs in eubacteria and lower
      eukaryotes and the absence of CSMs in archaebacteria suggests that DNA encoding
      CSMs has been transferred horizontally, possibly from multicellular organisms to
      bacteria.

PMID- 12788921
TI  - Characterization of the human prolyl 4-hydroxylases that modify the hypoxia
      inducible factor.
AB  - The hypoxia-inducible factors (HIFs) play a central role in oxygen homeostasis.
      Hydroxylation of one or two critical prolines by specific hydroxylases (P4Hs)
      targets their HIF-alpha subunits for proteasomal degradation. By studying the
      three human HIF-P4Hs, we found that the longest and shortest isoenzymes have
      major transcripts encoding inactive polypeptides, which suggest novel regulation
      by alternative splicing. Recombinant HIF-P4Hs expressed in insect cells required
      peptides of more than 8 residues, distinct differences being found between
      isoenzymes. All the HIF-P4Hs hydroxylated peptides corresponding to Pro564 in HIF
      1alpha, whereas a Pro402 peptide had 20-50-fold Km values for two isoenzymes but
      was not hydroxylated by the shortest isoenzyme at all; this difference was not
      explained by the two prolines being in a -Pro402-Ala- and -Pro564-Tyr-sequence.
      All the HIF-P4Hs-hydroxylated peptides corresponding to two of three potential
      sites in HIF-2alpha and one in HIF-3alpha. The Km values for O2 were slightly
      above its atmospheric concentration, indicating that the HIF-P4Hs are effective
      oxygen sensors. Small molecule inhibitors of collagen P4Hs also inhibited the HIF
      P4Hs, but with distinctly different Ki values, indicating that it should be
      possible to develop specific inhibitors for each class of P4Hs and possibly even
      for the individual HIF-P4Hs.

PMID- 12788922
TI  - X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the
      assembly of the C1 complex of complement.
AB  - C1, the complex that triggers the classical pathway of complement, is assembled
      from two modular proteases C1r and C1s and a recognition protein C1q. The N
      terminal CUB1-EGF segments of C1r and C1s are key elements of the C1
      architecture, because they mediate both Ca2+-dependent C1r-C1s association and
      interaction with C1q. The crystal structure of the interaction domain of C1s has
      been solved and refined to 1.5 A resolution. The structure reveals a head-to-tail
      homodimer involving interactions between the CUB1 module of one monomer and the
      epidermal growth factor (EGF) module of its counterpart. A Ca2+ ion is bound to
      each EGF module and stabilizes both the intra- and inter-monomer interfaces.
      Unexpectedly, a second Ca2+ ion is bound to the distal end of each CUB1 module,
      through six ligands contributed by Glu45, Asp53, Asp98, and two water molecules.
      These acidic residues and Tyr17 are conserved in approximately two-thirds of the
      CUB repertoire and define a novel, Ca2+-binding CUB module subset. The C1s
      structure was used to build a model of the C1r-C1s CUB1-EGF heterodimer, which in
      C1 connects C1r to C1s and mediates interaction with C1q. A structural model of
      the C1q/C1r/C1s interface is proposed, where the rod-like collagen triple helix
      of C1q is accommodated into a groove along the transversal axis of the C1r-C1s
      heterodimer.

PMID- 12788923
TI  - A new fungal lectin recognizing alpha(1-6)-linked fucose in the N-glycan.
AB  - In this report, we describe a new lectin from the fungus Rhizopus stolonifer that
      agglutinates rabbit red blood cells. Agglutinating activity was detected in the
      extract of mycelium-forming spores cultured on agar plates but not in the
      mycelium-forming no spores from liquid medium. This lectin, which we designated
      R. stolonifer lectin (RSL), was isolated by affinity chromatography with porcine
      stomach mucin-Sepharose. SDS-polyacrylamide gel electrophoresis and mass spectral
      analysis showed that RSL is approximately 4.5 kDa, whereas gel filtration
      indicated a mass of 28 kDa. This indicates that the lectin is a hexamer of
      noncovalently associated RSL monomers. RSL activity was very stable, since it was
      insensitive to heat treatment at 70 degrees C for 10 min. Analysis of RSL binding
      specificity by both microtiter plate and precipitation assays showed that N
      glycans with l-fucose linked to the reducing terminal GlcNAc residues are the
      most potent inhibitors of RSL binding, whereas N-glycans without alpha(1-6)
      linked fucose residues are approximately 100-fold weaker inhibitors of binding.
      Oligosaccharides with alpha(1-2, -3, and -4) linkages showed no inhibition of
      binding in these assays. In a mirror resonance biosensor assay, high affinity
      binding was observed between RSL and the glycopeptide of bovine gamma-globulin,
      which has N-glycans with alpha(1-6)-linked fucose residues. However, RSL showed
      only a weak interaction with the glycopeptide of quail ovomucoid, which lacks
      fucose residues. Finally, capillary affinity electrophoresis studies indicated
      that RSL binds strongly to N-glycans with alpha(1-6)-linked fucose residues.
      Together, these results show that RSL recognizes the core structure of N-glycans
      with alpha(1-6)-linked l-fucose residues. This specificity could make RSL a
      valuable tool for glycobiological studies.

PMID- 12788924
TI  - Autocrine growth factor regulation of lysyl oxidase expression in transformed
      fibroblasts.
AB  - Lysyl oxidase catalyzes oxidative deamination of peptidyl-lysine and
      hydroxylysine residues in collagens and lysine residues in elastin to form
      peptidyl aldehydes that are required for the formation of covalent cross-links in
      normal extracellular matrix biosynthesis. Lysyl oxidase in addition has tumor
      suppressor activity, and phenotypic reversion of transformed cell lines is
      accompanied by increased lysyl oxidase expression. The mechanism of low
      expression of lysyl oxidase in tumor cells is unknown. The present study
      investigates the hypothesis that autocrine growth factor pathways maintain low
      lysyl oxidase expression levels in c-H-ras-transformed fibroblasts (RS485 cell
      line). Autocrine pathways were blocked with suramin, a general inhibitor of
      growth factor receptor binding, and resulted in more than a 10-fold increase in
      lysyl oxidase expression and proenzyme production. This regulation was found to
      be reversible and occurred at the transcriptional level determined using lysyl
      oxidase promoter/reporter gene assays. Function blocking anti-fibroblast growth
      factor-2 (FGF-2) antibody enhanced lysyl oxidase expression in the absence of
      suramin. Finally, the addition of FGF-2 to suramin-treated cells completely
      reversed suramin stimulation of lysyl oxidase mRNA levels. Data support that an
      FGF-2 autocrine pathway inhibits lysyl oxidase transcription in the tumorigenic
      transformed RS485 cell line. This finding may be of therapeutic significance and,
      in addition, provides a new experimental approach to investigate the mechanism of
      the tumor suppressor activity of lysyl oxidase.

PMID- 12788925
TI  - Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin
      structures in the absence of DNA methylation.
AB  - MeCP2 is a transcriptional repressor that contains an N-terminal methylated DNA
      binding domain, a central transcription regulation domain, and a C-terminal
      domain of unknown function. Whereas current models of MeCP2 function evoke
      localized recruitment of histone deacetylases to specific methylated regions of
      the genome, it is unclear whether MeCP2 requires DNA methylation to bind to
      chromatin or whether MeCP2 binding influences chromatin structure in the absence
      of other proteins. To address these issues, we have characterized the complexes
      formed between MeCP2 and biochemically defined nucleosomal arrays. At molar
      ratios near 1 MeCP2/nucleosome, unmethylated nucleosomal arrays formed both
      extensively condensed ellipsoidal particles and oligomeric suprastructures.
      Furthermore, MeCP2-mediated chromatin compaction occurred in the absence of
      monovalent or divalent cations, in distinct contrast to all other known chromatin
      condensing proteins. Analysis of specific missense and nonsense MeCP2 mutants
      indicated that the ability to condense chromatin resides in region(s) of the
      protein other than the methylated DNA-binding domain. These data demonstrate that
      MeCP2 assembles novel secondary chromatin structures independent of DNA
      modification and suggest that the ability of MeCP2 to silence chromatin may be
      related in part to its effects on large-scale chromatin organization.

PMID- 12788927
TI  - Intermediary metabolism and energetics during murine early embryogenesis.

PMID- 12788926
TI  - Template recognition and formation of initiation complexes by the replicase of a
      segmented double-stranded RNA virus.
AB  - Replication of the segmented double-stranded (ds) RNA genome of viruses belonging
      to the Reoviridae family requires the RNA-dependent RNA polymerase (RdRP) to use
      10-12 different mRNAs as templates for (-) strand synthesis. Rotavirus serves as
      a model system for study of this process, since its RdRP (VP1) is catalytically
      active and can specifically recognize template mRNAs in vitro. Here, we have
      analyzed the requirements for template recognition by the rotavirus RdRP and
      compared those to the requirements for formation of (-) strand initiation
      complexes. The results show that multiple functionally independent recognition
      signals are present at the 3'-end of viral mRNAs, some positioned in nonconserved
      regions upstream of the highly conserved 3'-terminal consensus sequence. We also
      found that RdRP recognition signals are distinct from cis-acting signals that
      promote (-) strand synthesis, because deletions of portions of the 3'-consensus
      sequence that caused viral mRNAs to be poorly replicated in vitro did not
      necessarily prevent efficient recognition of the RNA by the RdRP. Although the
      RdRP alone can specifically bind to viral mRNAs, our analysis reveals that this
      interaction is not sufficient to generate initiation complexes, even in the
      presence of nucleotides and divalent cations. Rather, the formation of initiation
      complexes also requires the core lattice protein (VP2), a virion component that
      forms a T = 1 icosahedral shell that encapsidates the segmented dsRNA genome. The
      essential role that the core lattice protein has in (-) strand initiation
      provides a mechanism for the coordination of genome replication and virion
      assembly.

PMID- 12788928
TI  - In vivo mutagenesis of the insulin receptor.
AB  - Mice bearing targeted gene mutations that affect insulin receptor (Insr) function
      have contributed important new information on the pathogenesis of type 2
      diabetes. Whereas complete Insr ablation is lethal, conditional mutagenesis in
      selected tissues has more limited consequences on metabolism. Studies of mice
      with tissue-specific ablation of Insr have indicated that both canonical (e.g.
      muscle and adipose tissue) and noncanonical (e.g. liver, pancreatic beta-cells,
      and brain) insulin target tissues can contribute to insulin resistance, albeit in
      a pathogenically distinct fashion. Furthermore, experimental crosses of Insr
      mutants with mice carrying mutations that affect insulin action at more distal
      steps of the insulin signaling cascade have begun to unravel the genetics of type
      2 diabetes. These studies are consistent with an oligogenic inheritance, in which
      synergistic interactions among few alleles may account for the genetic
      susceptibility to diabetes. In addition to mutant alleles conferring an increased
      risk of diabetes, these studies have uncovered mutations that protect against
      insulin resistance, thus providing proof-of-principle for the notion that certain
      alleles may confer resistance to diabetes.

PMID- 12788929
TI  - Beta-Adrenergic receptors, diet-induced thermogenesis, and obesity.

PMID- 12788931
TI  - Glyceroneogenesis and the triglyceride/fatty acid cycle.

PMID- 12788920
TI  - Transcriptional regulation of biomass-degrading enzymes in the filamentous fungus
      Trichoderma reesei.
AB  - The filamentous fungus Trichoderma reesei produces and secretes profuse
      quantities of enzymes that act synergistically to degrade cellulase and related
      biomass components. We partially sequenced over 5100 random T. reesei cDNA
      clones. Among the sequences whose predicted gene products had significant
      similarity to known proteins, 12 were identified that encode previously unknown
      enzymes that likely function in biomass degradation. Microarrays were used to
      query the expression levels of each of the sequences under different conditions
      known to induce cellulolytic enzyme synthesis. Most of the genes encoding known
      and putative biomass-degrading enzymes were transcriptionally co-regulated.
      Moreover, despite the fact that several of these enzymes are not thought to
      degrade cellulase directly, they were coordinately overexpressed in a cellulase
      overproducing strain. A variety of additional sequences whose function could not
      be ascribed using the limited sequence available displayed analogous behavior and
      may also play a role in biomass degradation or in the synthesis of biomass
      degrading enzymes. Sequences exhibiting additional regulatory patterns were
      observed that might reflect roles in regulation of cellulase biosynthesis.
      However, genes whose products are involved in protein processing and secretion
      were not highly regulated during cellulase induction.

PMID- 12788932
TI  - Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor
      challenges assumptions about insulin action and glucose homeostasis.

PMID- 12788933
TI  - Gene-altered mice and metabolic flux control.

PMID- 12788934
TI  - Angiogenesis in collagen I requires alpha2beta1 ligation of a GFP*GER sequence
      and possibly p38 MAPK activation and focal adhesion disassembly.
AB  - Angiogenesis depends on proper collagen biosynthesis and cross-linking, and type
      I collagen is an ideal angiogenic scaffold, although its mechanism is unknown. We
      examined angiogenesis using an assay wherein confluent monolayers of human
      umbilical vein endothelial cells were overlain with collagen in a serum-free
      defined medium. Small spaces formed in the cell layer by 2 h, and cells formed
      net-like arrays by 6-8 h and capillary-like lumens by 24 h. Blocking of
      alpha2beta1, but not alpha1 or alpha(v)beta3 integrin function halted
      morphogenesis. We found that a triple-helical, homotrimeric peptide mimetic of a
      putative alpha2beta1 binding site: alpha1(I)496-507 GARGERGFP*GER (where single
      letter amino acid nomenclature is used, P* = hydroxyproline) inhibited tube
      formation, whereas a peptide carrying another putative site: alpha1(I)127-138
      GLP*GERGRP*GAP* or control peptides did not. A chemical inhibitor of p38 mitogen
      activated protein kinase (p38 MAPK), SB202190, blocked tube formation, and p38
      MAPK activity was increased in collagen-treated cultures, whereas targeting MAPK
      kinase (MEK), focal adhesion kinase (FAK), or phosphatidylinositol 3-kinase
      (PI3K) had little effect. Collagen-treated cells had fewer focal adhesions and 3-
      to 5-fold less activated FAK. Thus capillary morphogenesis requires endothelial
      alpha2beta1 integrin engagement of a single type I collagen integrin-binding
      site, possibly signaling via p38 MAPK and focal adhesion disassembly/FAK
      inactivation.

PMID- 12788935
TI  - Targeted disruption of a murine glucuronyl C5-epimerase gene results in heparan
      sulfate lacking L-iduronic acid and in neonatal lethality.
AB  - The glycosaminoglycan, heparan sulfate (HS), binds proteins to modulate signaling
      events in embryogenesis. All identified protein-binding HS epitopes contain l
      iduronic acid (IdoA). We report that targeted disruption of the murine d
      glucuronyl C5-epimerase gene results in a structurally altered HS lacking IdoA.
      The corresponding phenotype is lethal, with renal agenesis, lung defects, and
      skeletal malformations. Unexpectedly, major organ systems, including the brain,
      liver, gastrointestinal tract, skin, and heart, appeared normal. We find that
      IdoA units are essential for normal kidney, lung, and skeletal development,
      albeit with different requirement for 2-O-sulfation. By contrast, major early
      developmental events known to critically depend on heparan sulfate apparently
      proceed normally even in the absence of IdoA.

PMID- 12788936
TI  - Control of mitochondrial respiration by NO*, effects of low oxygen and
      respiratory state.
AB  - Nitric oxide (NO.) inhibits mitochondrial respiration by binding to the binuclear
      heme a3/CuB center in cytochrome c oxidase. However, the significance of this
      reaction at physiological O2 levels (5-10 microM) and the effects of respiratory
      state are unknown. In this study mitochondrial respiration, absorption spectra,
      [O2], and [NO.] were measured simultaneously at physiological O2 levels with
      constant O2 delivery, to model in vivo respiratory dynamics. Under these
      conditions NO. inhibited mitochondrial respiration with an IC50 of 0.14 +/- 0.01
      microm in state 3 versus 0.31 +/- 0.04 microM in state 4. Spectral data indicate
      that the higher sensitivity of state 3 respiration to NO. is due to greater
      control over respiration by an NO.-dependent spectral species in the respiratory
      chain in this state. These results are discussed in the context of regulation of
      respiration by NO. in vivo and its implications for the control of vessel
      parenchymal O2 gradients.

PMID- 12788937
TI  - Transcriptional regulation of the cytosolic chaperonin theta subunit gene, Cctq,
      by Ets domain transcription factors Elk-1, Sap-1a, and Net in the absence of
      serum response factor.
AB  - The chaperonin-containing t-complex polypeptide 1 (CCT) is a molecular chaperone
      that facilitates protein folding in eukaryotic cytosol, and the expression of CCT
      is highly dependent on cell growth. We show here that transcription of the gene
      encoding the theta subunit of mouse CCT, Cctq, is regulated by the ternary
      complex factors (TCFs), Elk-1, Sap-1a, and Net (Sap-2). Reporter gene assay using
      HeLa cells indicated that the Cctq gene promoter contains a cis-acting element of
      the CCGGAAGT sequence (CQE1) at -36 bp. The major CQE1-binding proteins in HeLa
      cell nuclear extract was recognized by anti-Elk-1 or anti-Sap-1a antibodies in
      electrophoretic mobility shift assay, and recombinant Elk-1, Sap-1a, or Net
      specifically recognized CQE1. The CQE1-dependent transcriptional activity in HeLa
      cells was virtually abolished by overexpression of the DNA binding domains of
      TCFs. Overexpression of full-length TCFs with Ras indicated that exogenous TCFs
      can regulate the CQE1-dependent transcription in a Ras-dependent manner. PD98059,
      an inhibitor of MAPK, significantly repressed the CQE1-dependent transcription.
      However, no serum response factor was detected by electrophoretic mobility shift
      assay using the CQE1 element. These results indicate that transcription of the
      Cctq gene is regulated by TCFs under the control of the Ras/MAPK pathway,
      probably independently of serum response factor.

PMID- 12788938
TI  - Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3:
      implications for the control of protein stability and PTEN-protein interactions.
AB  - PTEN phosphatase is one of the most commonly targeted tumor suppressors in human
      cancers and a key regulator of cell growth and apoptosis. We have found that PTEN
      is cleaved by caspase-3 at several target sites, located in unstructured regions
      within the C terminus of the molecule. Cleavage of PTEN was increased upon
      TNFalpha-cell treatment and was negatively regulated by phosphorylation of the C
      terminal tail of PTEN by the protein kinase CK2. The proteolytic PTEN fragments
      displayed reduced protein stability, and their capability to interact with the
      PTEN interacting scaffolding protein S-SCAM/MAGI-2 was lost. Interestingly, S
      SCAM/MAGI-2 was also cleaved by caspase-3. Our findings suggest the existence of
      a regulatory mechanism of protein stability and PTEN-protein interactions during
      apoptosis, executed by caspase-3 in a PTEN phosphorylation-regulated manner.

PMID- 12788939
TI  - Nuclear protein phosphatase-1 regulates HIV-1 transcription.
AB  - We recently reported that protein phosphatase 1 (PP1) dephosphorylates RNA
      polymerase II C-terminal repeats and regulates HIV-1 transcription in vitro. Here
      we provide evidence that PP1 is also required for Tat-induced HIV-1 transcription
      and for viral replication in cultured cells. Inhibition of PP1 by overexpression
      of nuclear inhibitor of PP1 (NIPP1) inhibited Tat-induced HIV-1 transcription in
      transient transfection assays. A mutant of NIPP1 that was defective in binding to
      PP1 did not have this effect. Also the co-expression of PP1 gamma reversed the
      inhibitory effect of NIPP1. Adeno-associated virus-mediated delivery of NIPP1
      significantly reduced HIV-1 transcription induced by Tat-expressing adenovirus in
      CD4+ HeLa cells that contained an integrated HIV-1 promoter (HeLa MAGI cells). In
      addition, infection of HeLa MAGI cells with adeno-associated virus-NIPP1 prior to
      the infection with HIV-1 significantly reduced the level of HIV-1 replication.
      Our results indicate that PP1 might be a host cell factor that is required for
      HIV-1 viral transcription. Therefore, nuclear PP1 may represent a novel target
      for anti-HIV-1 therapeutics.

PMID- 12788940
TI  - AMP-activated protein kinase (AMPK) signaling in endothelial cells is essential
      for angiogenesis in response to hypoxic stress.
AB  - AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that is
      regulated by hypoxia and other cellular stresses that result in diminished
      cellular ATP levels. Here, we investigated whether AMPK signaling in endothelial
      cells has a role in regulating angiogenesis. Hypoxia induced the activating
      phosphorylation of AMPK in human umbilical vein endothelial cells (HUVECs), and
      AMPK activation was required for the maintenance of pro-angiogenic Akt signaling
      under these conditions. Suppression of AMPK signaling inhibited both HUVEC
      migration to VEGF and in vitro differentiation into tube-like structures in
      hypoxic, but not normoxic cultures. Dominant-negative AMPK also inhibited in vivo
      angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. These
      data identify AMPK signaling as a new regulator of angiogenesis that is
      specifically required for endothelial cell migration and differentiation under
      conditions of hypoxia. As such, endothelial AMPK signaling may be a critical
      determinant of blood vessel recruitment to tissues that are subjected to ischemic
      stress.

PMID- 12788941
TI  - SAMP14, a novel, acrosomal membrane-associated, glycosylphosphatidylinositol
      anchored member of the Ly-6/urokinase-type plasminogen activator receptor
      superfamily with a role in sperm-egg interaction.
AB  - We report a new member of the Ly-6/urokinase-type plasminogen activator receptor
      (uPAR) superfamily of receptors, SAMP14, which is retained on the inner acrosomal
      membrane of the human spermatozoan following the acrosome reaction and may play a
      role in fertilization. The SAMP14 sequence predicted a
      glycosylphosphatidylinositol (GPI)-anchored protein with a signal peptide, a
      transmembrane domain near the carboxyl terminus, and a putative transamidase
      cleavage site in the proprotein. Attachment of SAMP14 to the membrane by a lipid
      anchor was confirmed by its sensitivity to phosphatidylinositol phospholipase C.
      SAMP14 has a single functional domain similar to the Ly-6 and urokinase
      plasminogen activator receptor superfamily of proteins, and the gene mapped to
      19q13.33, near the PLAUR locus for uPAR at 19q13.2. Northern and dot blotting
      showed that SAMP14 expression was testis-specific. Indirect immunofluorescence
      and immunoelectron microscopy with antisera to purified recombinant SAMP14
      localized the protein to outer and inner acrosomal membranes as well as the
      acrosomal matrix of ejaculated human sperm. Acrosome-reacted sperm demonstrated
      SAMP14 immunofluorescence, indicating its retention on the inner acrosomal
      membrane following the acrosome reaction. However, SAMP14 localized to the entire
      sperm when unwashed swim-up sperm from the ejaculate were stained, indicating
      that some SAMP14 is loosely associated with the plasma membrane. Antibodies
      against recombinant SAMP14 inhibited both the binding and the fusion of human
      sperm to zona free hamster eggs, suggesting that SAMP14 may have a role in sperm
      egg interaction. SAMP14 represents a GPI-anchored putative receptor in the Ly
      6/uPAR family that is exposed on the inner acrosomal membrane after the acrosome
      reaction.

PMID- 12788942
TI  - The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1),
      interacts with the polycomb group protein, embryonic ectoderm development (EED),
      and functions as a transcriptional repressor.
AB  - The nuclear protein NIPP1 (nuclear inhibitor of protein Ser/Thr phosphatase-1)
      interacts with the splicing factors SAP155 and CDC5L and is involved in a late
      step of spliceosome assembly. In addition, NIPP1 is an interactor of protein
      phosphatase-1 and a COOH-terminal NIPP1 fragment displays an RNase E like
      endoribonuclease activity. A yeast two-hybrid screening resulted in the
      identification of the Polycomb group protein EED (embryonic ectoderm
      development), an established transcriptional repressor, as a novel NIPP1
      interactor. NIPP1 only interacted with full-length EED, whereas two EED
      interaction domains were mapped to the central and COOH-terminal thirds of NIPP1.
      The NIPP1-EED interaction was potentiated by the binding of (d)G-rich nucleic
      acids to the central domain of NIPP1. Nucleic acids also decreased the potency of
      NIPP1 as an inhibitor of PP1, but they did not prevent the formation of a ternary
      NIPP1.EED.PP1 complex. EED had no effect on the function of NIPP1 as a splicing
      factor or as an endoribonuclease. However, similar to EED, NIPP1 acted as a
      transcriptional repressor of targeted genes and this NIPP1 effect was mediated by
      the EED interaction domain. Also, the histone deacetylase 2 was present in a
      complex with NIPP1. Our data are in accordance with a role for NIPP1 as a DNA
      targeting protein for EED and associated chromatin-modifying enzymes.

PMID- 12788943
TI  - Mutagenesis reveals a specific role for Cox17p in copper transport to cytochrome
      oxidase.
AB  - The provision of copper to cytochrome oxidase is one of the requisite steps in
      the assembly of the holoenzyme. Several proteins are involved in this process
      including Cox17p, Sco1p, and Cox11p. Cox17p, an 8-kDa protein, is the only
      molecule thought to be involved in shuttling copper from the cytoplasm into
      mitochondria. Given the small size of Cox17p, we have taken a random and site
      directed mutagenesis approach to studying structure-function relationships in
      Cox17p. Mutations have been generated in 70% of the Cox17p amino acid residues,
      with only a small subset leading to a detectable respiration-deficient phenotype.
      We have characterized the respiration-deficient cox17 mutants and found in
      addition to the expected cytochrome oxidase deficiency, a specific lack of Cox2p
      and the presence of a misassembled cytochrome oxidase in a subset of mutants.
      These results suggest that Cox17p is involved upstream of Sco1p in delivering
      copper specifically to subunit 2 of cytochrome oxidase and predict the existence
      of a subunit 1-specific copper chaperone.

PMID- 12788944
TI  - The association of the human PM/Scl-75 autoantigen with the exosome is dependent
      on a newly identified N terminus.
AB  - The exosome is a complex of 3' --> 5' exoribonucleases that functions in a
      variety of cellular processes, all concerning the processing or degradation of
      RNA. Paradoxically, the previously described cDNA for the human autoantigenic
      exosome subunit PM/Scl-75 (Alderuccio, F., Chan, E. K., and Tan, E. M. (1991) J.
      Exp. Med. 173, 941-952) encodes a polypeptide that failed to interact with the
      exosome complex. Here, we describe the cloning of a more complete cDNA for PM/Scl
      75 encoding 84 additional amino acids at its N terminus. We show that only the
      longer polypeptide is able to associate with the exosome complex. This
      interaction is most likely mediated by protein-protein interactions with two
      other exosome subunits, hRrp46p and hRrp41p, one of which was confirmed in a
      mammalian two-hybrid system. In addition we show that the putative nuclear
      localization signal present in the C-terminal region of PM/Scl-75 is sufficient,
      although not essential for nuclear localization of the protein. Moreover, the
      deletion of this element abrogated the nucleolar accumulation of PM/Scl-75,
      although its association with the exosome was not disturbed. This suggests that
      this basic element of PM/Scl-75 plays a role in targeting the exosome to the
      nucleolus.

PMID- 12788945
TI  - Proanthocyanidin biosynthesis in plants. Purification of legume
      leucoanthocyanidin reductase and molecular cloning of its cDNA.
AB  - Leucoanthocyanidin reductase (LAR) catalyzes the synthesis of catechin, an
      initiating monomer of condensed tannin or proanthocyanidin (PA) synthesis, from
      3,4-cis-leucocyanidin and thus is the first committed step in PA biosynthesis.
      The enzyme was purified to near homogeneity from PA-rich leaves of the legume
      Desmodium uncinatum (Jacq.) DC, partially sequenced and the corresponding cDNA
      cloned. The identity of the enzyme was confirmed by expressing active recombinant
      LAR in Escherichia coli and in tobacco and white clover. The enzyme is a monomer
      of 43 kDa (382 amino acids) and is most active synthesizing catechin (specific
      activity of approximately 10 micromol min+1 mg of protein+1) but also synthesizes
      afzelechin and gallocatechin. LAR is most closely related to the isoflavone
      reductase group of plant enzymes that are part of the Reductase-Epimerase
      Dehydrogenase (RED) family of proteins. Unlike all other plant isoflavone
      reductase homologues that are about 320 amino acids long, LAR has an additional
      65-amino acid C-terminal extension whose function is not known. Curiously,
      although Arabidopsis makes PA, there is no obvious LAR orthologue in the
      Arabidopsis genome. This may be because Arabidopsis seems to produce only an
      epicatechin, rather than a dual catechin/epicatechin-based PA similar to many
      other plants.

PMID- 12788946
TI  - Homodimeric quaternary structure is required for the in vivo function and thermal
      stability of Saccharomyces cerevisiae and Schizosaccharomyces pombe RNA
      triphosphatases.
AB  - Saccharomyces cerevisiae Cet1 and Schizosaccharomyces pombe Pct1 are the
      essential RNA triphosphatase components of the mRNA capping apparatus of budding
      and fission yeast, respectively. Cet1 and Pct1 share a baroque active site
      architecture and a homodimeric quaternary structure. The active site is located
      within a topologically closed hydrophilic beta-barrel (the triphosphate tunnel)
      that rests on a globular core domain (the pedestal) composed of elements from
      both protomers of the homodimer. Earlier studies of the effects of alanine
      cluster mutations at the crystallographic dimer interface of Cet1 suggested that
      homodimerization is important for triphosphatase function in vivo, albeit not for
      catalysis. Here, we studied the effects of 14 single-alanine mutations on Cet1
      activity and thereby pinpointed Asp280 as a critical side chain required for
      dimer formation. We find that disruption of the dimer interface is lethal in vivo
      and renders Cet1 activity thermolabile at physiological temperatures in vitro. In
      addition, we identify individual residues within the pedestal domain (Ile470,
      Leu519, Ile520, Phe523, Leu524, and Ile530) that stabilize Cet1 in vivo and in
      vitro. In the case of Pct1, we show that dimerization depends on the peptide
      segment 41VPKIEMNFLN50 located immediately prior to the start of the Pct1
      catalytic domain. Deletion of this peptide converts Pct1 into a catalytically
      active monomer that is defective in vivo in S. pombe and hypersensitive to
      thermal inactivation in vitro. Our findings suggest an explanation for the
      conservation of quaternary structure in fungal RNA triphosphatases, whereby the
      delicate tunnel architecture of the active site is stabilized by the homodimeric
      pedestal domain.

PMID- 12788947
TI  - Structural requirements for expression of factor Va activity.
AB  - Thrombin activated factor Va (factor VIIa, residues 1-709 and 1546-2196) has an
      apparent dissociation constant (Kd,app) for factor Xa within prothrombinase of
      approximately 0.5 nM. A protease (NN) purified from the venom of the snake Naja
      nigricollis nigricollis, cleaves human factor V at Asp697, Asp1509, and Asp1514
      to produce a molecule (factor VNN) that is composed of a Mr 100,000 heavy chain
      (amino acid residues 1-696) and a Mr 80,000 light chain (amino acid residues
      1509/1514-2196). Factor VNN, has a Kd,app for factor Xa of 4 nm and reduced
      clotting activity. Cleavage of factor VIIa by NN at Asp697 results in a cofactor
      that loses approximately 60-80% of its clotting activity. An enzyme from
      Russell's viper venom (RVV) cleaves human factor V at Arg1018 and Arg1545 to
      produce a Mr 150,000 heavy chain and Mr 74,000 light chain (factor VRVV, residues
      1-1018 and 1546-2196). The RVV species has affinity for factor Xa and clotting
      activity similar to the thrombin-activated factor Va. Cleavage of factor VNN at
      Arg1545 by alpha-thrombin (factor VNN/IIa) or RVV (factor VNN/RVV) leads to
      enhanced affinity of the cofactor for factor Xa (Kd,app approximately 0.5 nM). A
      synthetic peptide containing the last 13 residues from the heavy chain of factor
      Va (amino acid sequence 697-709, D13R) was found to be a competitive inhibitor of
      prothrombinase with respect to prothrombin. The peptide was also found to
      specifically interact with thrombin-agarose. These data demonstrate that 1)
      cleavage at Arg1545 and formation of the light chain of factor VIIa is essential
      for high affinity binding and function of factor Xa within prothrombinase and 2)
      a binding site for prothrombin is contributed by amino acid residues 697-709 of
      the heavy chain of the cofactor.

PMID- 12788948
TI  - Identification and characterization of the cytoplasmic protein TRAF4 as a p53
      regulated proapoptotic gene.
AB  - The role of p53 in tumor suppression partly relies on its ability to
      transcriptionally regulate target genes involved in the initiation of cell cycle
      arrest or the activation of programmed cell death. In recent years many genes
      have been identified as p53-regulated genes; however, no single target gene has
      been shown to be required for the full apoptotic effect. We have identified TRAF4
      as a p53-regulated gene in a microarray screen using a Murine 11K Affymetrix
      GeneChip hybridized with cRNA from the p53 temperature-sensitive cell line, Vm10.
      TRAF4 is a member the TRAF family of adaptor proteins that mediate cellular
      signaling by binding to various members of the tumor necrosis family receptor
      superfamily and interleukin-1/Toll-like receptor super-family. In contrast to its
      other family members, TRAF4 has not been shown to bind to a member of the tumor
      necrosis factor receptor superfamily in vivo, nor has it been shown to regulate
      signaling pathways common to its other family members. Therefore the role of
      TRAF4 in a signaling pathway has not yet been established and requires further
      study. TRAF4 is specifically regulated by p53 in response to temperature
      sensitive p53, overexpression of p53 by use of an adenovirus, and stabilization
      of p53 in response to DNA damage. The murine TRAF4 promoter contains a functional
      p53 DNA-binding site approximately 1 kilobase upstream of the initiating
      methionine. TRAF4 localizes to the cytoplasm and appears to remain in the
      cytoplasm following DNA damage. Interestingly, the overexpression of TRAF4
      induces apoptosis and suppresses colony formation. These data suggest a
      correlation that the orphan adaptor protein TRAF4 may play a role in p53-mediated
      proapoptotic signaling in the response to cellular stress.

PMID- 12788949
TI  - Genetic analysis of the myotubularin family of phosphatases in Caenorhabditis
      elegans.
AB  - Myotubularins (MTMs) constitute a large family of lipid phosphatases that
      specifically dephosphorylate phosphatidylinositol (3)P. MTM1 and MTM2 are mutated
      in X-linked myotubular myopathy and Charcot-Marie-Tooth disease (type 4B),
      respectively, although the mechanisms whereby MTM dysfunction leads to these
      diseases is unknown. To gain insight into MTM function, we undertook the study of
      MTMs in the nematode Caenorhabditis elegans, which possesses representative
      homologues of the four major subgroups of MTMs identified in mammals. As in
      mammals, we found that C. elegans MTMs mediate distinct functions. let-512
      (vps34) encodes the C. elegans homologue of the yeast and mammalian homologue of
      the phosphatidylinositol 3-kinase Vps34. We found that reduction of mtm-6
      (F53A2.8) function by RNA inhibition rescued the larval lethality of let-512
      (vps34) mutants and that the reduction of mtm-1 (Y110A7A.5) activity by RNA
      inhibition rescued the endocytosis defect of let-512 animals. Together, these
      observations provide genetic evidence that MTMs negatively regulate
      phosphatidylinositol (3)P levels. Analysis of MTM expression patterns using
      transcriptional green fluorescence protein reporters demonstrated that these two
      MTMs exhibit mostly non-overlapping expression patterns and that MTM-green
      fluorescence protein fusion proteins are localized to different subcellular
      locations. These observations suggest that some of the different functions of
      MTMs might, in part, be a consequence of unique expression and localization
      patterns. However, our finding that at least three C. elegans MTMs play essential
      roles in coelomocyte endocytosis, a process that also requires VPS34, indicates
      that MTMs do not simply turn off VPS34 but unexpectedly also function as positive
      regulators of biological processes.

PMID- 12788950
TI  - Direct interaction between Escherichia coli RNA polymerase and the zinc ribbon
      domains of DNA topoisomerase I.
AB  - Escherichia coli DNA topoisomerase I (encoded by the topA gene) is important for
      maintaining steady-state DNA supercoiling and has been shown to influence vital
      cellular processes including transcription. Topoisomerase I activity is also
      needed to remove hypernegative supercoiling generated on the DNA template by the
      progressing RNA polymerase complex during transcription elongation. The
      accumulation of hypernegative supercoiling in the absence of topoisomerase I can
      lead to R-loop formation by the nascent transcript and template strand, leading
      to suppression of transcription elongation. Here we show by affinity
      chromatography and overlay blotting that E. coli DNA topoisomerase I interacts
      directly with the RNA polymerase complex. The protein-protein interaction
      involves the beta' subunit of RNA polymerase and the C-terminal domains of E.
      coli DNA topoisomerase I, which are homologous to the zinc ribbon domains in a
      number of transcription factors. This direct interaction can bring the
      topoisomerase I relaxing activity to the site of transcription where its activity
      is needed. The zinc ribbon C-terminal domains of other type IA topoisomerases,
      including mammalian topoisomerase III, may also help link the enzyme activities
      to their physiological functions, potentially including replication,
      transcription, recombination, and repair.

PMID- 12788951
TI  - Refolding of substrates bound to small Hsps relies on a disaggregation reaction
      mediated most efficiently by ClpB/DnaK.
AB  - Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that bind
      denatured proteins in vitro, thereby facilitating their subsequent refolding by
      ATP-dependent chaperones. The mechanistic basis of this refolding process is
      poorly defined. We demonstrate that substrates complexed to sHsps from various
      sources are not released spontaneously. Dissociation and refolding of sHsp bound
      substrates relies on a disaggregation reaction mediated by the DnaK system, or,
      more efficiently, by ClpB/DnaK. While the DnaK system alone works for small,
      soluble sHsp/substrate complexes, ClpB/DnaK-mediated protein refolding is fastest
      for large, insoluble protein aggregates with incorporated sHsps. Such conditions
      reflect the situation in vivo, where sHsps are usually associated with insoluble
      proteins during heat stress. We therefore propose that sHsp function in cellular
      protein quality control is to promote rapid resolubilization of aggregated
      proteins, formed upon severe heat stress, by DnaK or ClpB/DnaK.

PMID- 12788952
TI  - Mice lacking phosphatidylinositol transfer protein-alpha exhibit spinocerebellar
      degeneration, intestinal and hepatic steatosis, and hypoglycemia.
AB  - Phosphatidylinositol transfer proteins (PITPs) regulate the interface between
      lipid metabolism and cellular functions. We now report that ablation of PITP
      alpha function leads to aponecrotic spinocerebellar disease, hypoglycemia, and
      intestinal and hepatic steatosis in mice. The data indicate that hypoglycemia is
      in part associated with reduced proglucagon gene expression and glycogenolysis
      that result from pancreatic islet cell defects. The intestinal and hepatic
      steatosis results from the intracellular accumulation of neutral lipid and free
      fatty acid mass in these organs and suggests defective trafficking of
      triglycerides and diacylglycerols from the endoplasmic reticulum. We propose that
      deranged intestinal and hepatic lipid metabolism and defective proglucagon gene
      expression contribute to hypoglycemia in PITP alpha-/- mice, and that
      hypoglycemia is a significant contributing factor in the onset of spinocerebellar
      disease. Taken together, the data suggest an unanticipated role for PITP alpha in
      with glucose homeostasis and in mammalian endoplasmic reticulum functions that
      interface with transport of specific luminal lipid cargoes.

PMID- 12788953
TI  - The NOG1 GTP-binding protein is required for biogenesis of the 60 S ribosomal
      subunit.
AB  - NOG1 is a nucleolar GTP-binding protein present in eukaryotes ranging from
      trypanosomes to humans. In this report we demonstrate that NOG1 is functionally
      linked to ribosome biogenesis. In sucrose density gradients Trypanosoma brucei
      NOG1 co-sediments with 60 S ribosomal subunits but not with monosomes. 60 S
      precursor RNAs are co-precipitated with NOG1. Together with the nucleolar
      localization of NOG1, these data indicate that NOG1 is associated with a
      precursor particle to the 60 S subunit. Disruption of NOG1 function through RNA
      interference led to a dramatic decrease in the levels of free 60 S particles and
      the appearance of an atypical rRNA intermediate in which ITS2 was not cleaved.
      Overexpression of mutant nog1 with a defect in its GTP binding motif on a wild
      type background caused a modest defect in 60 S biogenesis and a relative decrease
      in processing of the large subunit rRNAs. In contrast to the mutant protein,
      neither the N-terminal half of NOG1, which contains the GTP binding motifs, nor
      the C-terminal half of NOG1 associated with pre-ribosomal particles, although
      both localized to the nucleolus.

PMID- 12788954
TI  - Kinetic mechanism for formation of the active, dimeric UvrD helicase-DNA complex.
AB  - Escherichia coli UvrD protein is a 3' to 5' SF1 helicase required for DNA repair
      as well as DNA replication of certain plasmids. We have shown previously that
      UvrD can self-associate to form dimers and tetramers in the absence of DNA, but
      that a UvrD dimer is required to form an active helicase-DNA complex in vitro.
      Here we have used pre-steady state, chemical quenched flow methods to examine the
      kinetic mechanism for formation of the active, dimeric helicase-DNA complex.
      Experiments were designed to examine the steps leading to formation of the active
      complex, separate from the subsequent DNA unwinding steps. The results show that
      the active dimeric complex can form via two pathways. The first, faster path
      involves direct binding to the DNA substrate of a pre-assembled UvrD dimer (dimer
      path), whereas the second, slower path proceeds via sequential binding to the DNA
      substrate of two UvrD monomers (monomer path), which then assemble on the DNA to
      form the dimeric helicase. The rate-limiting step within the monomer pathway
      involves dimer assembly on the DNA. These results show that UvrD dimers that pre
      assemble in the absence of DNA are intermediates along the pathway to formation
      of the functional dimeric UvrD helicase.

PMID- 12788956
TI  - No confidence in the MRC.

PMID- 12788955
TI  - A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes
      with similar docking sites in JNK substrates.
AB  - Specific docking interactions between MAPKs and their activating MAPK kinases
      (MKKs or MEKs) are crucial for efficient and accurate signal transmission. Here,
      we report the identification of a MAPK-docking site, or "D-site," in the N
      terminus of human MKK4/JNKK1. This docking site conforms to the consensus
      sequence for known D-sites in other MKKs and contains the first of the two
      cleavage sites for anthrax lethal factor protease that have been found in the N
      terminus of MKK4. This docking site was both necessary and sufficient for the
      high affinity binding of the MAPKs JNK1, JNK2, JNK3, p38 alpha, and p38 beta to
      MKK4. Mutations that altered conserved residues in this docking site reduced
      JNK/p38 binding. In addition, a peptide version of this docking site, as well as
      a peptide version of the JNK-binding site of the JIP-1 scaffold protein,
      inhibited both MKK4/JNK binding and MKK4-mediated phosphorylation of JNK1. These
      same peptides also inhibited JNK2-mediated phosphorylation of c-Jun and ATF2,
      suggesting that transcription factors, MKK4, and the JIP scaffold compete for
      docking to JNK. Finally, the selectivity of the MKK4, MEK1, and MEK2 D-sites for
      JNK versus ERK was quantified. The MEK1 and MEK2 D-sites displayed a strong
      selectivity for their cognate MAPK (ERK2) versus a non-cognate MAPK (JNK). In
      contrast, the MKK4 D-site exhibited only limited selectivity for JNK versus ERK.

PMID- 12788958
TI  - The evolving role of sirolimus in renal transplantation.

PMID- 12788957
TI  - Recent developments in the treatment of alcoholic hepatitis.
AB  - Alcoholic hepatitis is a form of acute injury to liver tissue that is also a
      precursor of cirrhosis, and carries significant morbidity and mortality. Severe
      alcoholic hepatitis in particular carries a high short-term mortality, and also
      places an enormous burden on stretched healthcare resources. Treatment of
      alcoholic hepatitis has been limited to supportive management and nutritional
      supplementation without clear improvements in outcome, and the timing and patient
      selection for hepatic transplantation is problematic. The use of corticosteroids
      has remained controversial for many years, but probably has a role in selected
      patients. Various other therapeutic strategies have been tested over the decades
      and none has shown any consistent benefit. Recently there have been major
      developments in our understanding of the mechanisms of alcoholic liver injury,
      including the role of cytokines and hepatocyte apoptosis. For the first time,
      there are exciting possibilities for specific therapies for this challenging and
      serious condition.

PMID- 12788959
TI  - Powerful morphometric indicator of prognosis in lupus nephritis.
AB  - BACKGROUND: Changes in renal biopsies in lupus nephritis have been analysed in
      many ways, but few have had prognostic value. AIM: To see whether a morphometric
      measure of chronic renal damage that was a prognostic indicator in other
      conditions had similar value in lupus nephritis. DESIGN: Retrospective analysis
      of biopsies and study of outcome. METHODS: On sections of 260 biopsies from 182
      consecutive patients with systemic lupus erythematosus, an image analysis system
      measured chronic damage as a proportion of cortical area, to give the index of
      chronic damage. This was related to survival (until death or onset of dialysis).
      Patients were followed for up to 20 years. RESULTS: The index of chronic damage
      ranged from 0 to 93%. Twenty-three patients (13%) died before dialysis, many from
      infection or myocardial infarction, and 40 (22%) went onto permanent dialysis.
      There were strong correlations between the index and time until death or dialysis
      (log rank test: chi(2) = 51.08, three degrees of freedom [df], p < 0.001) and
      time to dialysis (log rank test: chi(2) = 72.88, 3df, p < 0.001), but there was
      no correlation with time until death before dialysis (log rank test: chi(2) =
      0.36, 3df, p > 0.9). WHO class of nephritis had no major relation to outcome
      after the index was taken into account and after appropriate treatment of the
      different classes. DISCUSSION: The index was a strong indicator of risk of
      progression to renal failure in lupus nephritis, but not of risk of death before
      dialysis. This will be useful in clinical management and treatment trials.

PMID- 12788960
TI  - Solute loss plays a major role in polydipsia-related hyponatraemia of both water
      drinkers and beer drinkers.
AB  - BACKGROUND: Polydipsia-related hyponatraemia is generally considered an acute
      dilutional state. AIM: To determine whether solute loss plays a role in the
      pathogenesis of polydipsia-related hyponatraemia. DESIGN: Prospective
      uncontrolled study. METHODS: We studied routine biochemical volume-related
      parameters before and after 2 l isotonic saline infusion over 24 h, in 10
      consecutive hyponatraemic polydipsia patients (mean age 55 +/- 11 years; 6 beer
      drinkers and 4 compulsive water drinkers) with initial urinary osmolality <220
      mosm/kg H(2)O. In five of these patients, we measured balance data over 24 h.
      RESULTS: Mean initial plasma protein concentration in the 10 studied polydipsia
      patients was 7 +/- 0.7 g/dl, unexpectedly high for an acute dilutional state.
      Mean plasma sodium concentration increased from 126 +/- 5 mmol/l before saline,
      to 135 +/- 5 mmol/l after infusion of 2 l isotonic saline (p < 0.01). Balance
      data in five polydipsia patients showed a mean decrease of 1.6 kg of their
      initial body weight and a mean salt retention of 406 mosm. DISCUSSION: Polydipsia
      related hyponatraemia is a mixed disorder, in which about half of sodium decrease
      is due to solute loss. This explains the apparent paradox of a normal plasma
      protein concentration, despite the increase in body weight due to water
      intoxication.

PMID- 12788961
TI  - Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia.
AB  - BACKGROUND: The role of volume resuscitation in severe Plasmodium falciparum
      malaria is controversial. AIM: To examine the role of hypovolaemia in severe
      childhood malaria. STUDY DESIGN: Retrospective review. METHODS: We studied 515
      children admitted with severe malaria to a high-dependency unit (HDU) in Kilifi,
      Kenya. On admission to the HDU, children underwent a further assessment of vital
      signs and a standard clinical examination. RESULTS: Factors associated with a
      fatal outcome included deep breathing or acidosis (base excess below -8),
      hypotension (systolic blood pressure <80 mmHg), raised plasma creatinine (>80
      micro mol/l), low oxygen saturation (<90%), dehydration and hypoglycaemia (<2.5
      mmol/l). Shock was present in 212/372 (57%) children, of whom 37 (17.5%) died,
      and was absent in 160, of who only 7 (4.4%) died (chi(2) = 14.9; p = 0.001).
      DISCUSSION: Impaired tissue perfusion may play a role in the mortality of severe
      malaria. Moreover, volume resuscitation, an important life-saving intervention in
      children with hypovolaemia, should be considered in severe malaria with evidence
      of impaired tissue perfusion.

PMID- 12788962
TI  - Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to
      inhaled corticosteroids.
AB  - BACKGROUND: The protection afforded by long-acting beta(2)-agonists against
      bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing
      effects on airway smooth muscle. AIM: To determine the magnitude of residual
      bronchoprotection after chronic dosing with long-acting beta(2)-agonists. DESIGN:
      Retrospective meta-analysis. METHODS: Medline, BIDS and Cochrane Library
      databases were searched from 1990. A meta-analysis was then performed of 13
      eligible randomized placebo-controlled trials (596 patients) in which second-line
      treatment with a long-acting beta(2)-agonist (salmeterol or formoterol) was used
      for 1 week or more. The residual protection against bronchoconstrictor stimuli as
      doubling dose/dilution shift was the main outcome measure. RESULTS: Data were
      assessed according to Quorum criteria. Combining the results of the meta
      analysis, the overall estimated protection amounted to a 0.79 (95%CI 0.63-0.96)
      doubling dose/dilution shift from placebo. Subgroup analysis showed greater
      protection at peak vs. trough, but no difference between formoterol vs.
      salmeterol, or between direct vs. indirect challenge. There was no evidence of
      significant heterogeneity across all the studies, or within any of the subgroups.
      DISCUSSION: When used as second-line treatment, the overall additive protective
      effect of long-acting beta(2)-agonists amounts to a 0.8 doubling dose/dilution
      shift. This stabilizing effect on airway smooth muscle may explain their
      beneficial effects on exacerbations.

PMID- 12788963
TI  - Waist circumference, waist-to-hip ratio and body mass index as predictors of
      adipose tissue compartments in men.
AB  - BACKGROUND: The accumulation of fat in visceral and posterior subcutaneous
      adipose tissue compartments is highly correlated with the metabolic abnormalities
      that contribute to increased risk of diabetes mellitus and cardiovascular
      disease. AIM: To determine which of waist circumference (WC), waist-to-hip ratio
      (WHR) and body mass index (BMI) was the best predictor of intraperitoneal and
      posterior subcutaneous abdominal adipose tissue mass in men. METHODS: We studied
      59 free-living men with a wide range of BMI. WC, WHR and BMI were determined
      using standard methods. Intraperitoneal, retroperitoneal, anterior subcutaneous
      and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, ASAATM
      and PSAATM, respectively) were quantified using magnetic resonance imaging.
      RESULTS: In univariate regression analysis, WC, WHR and BMI were all
      significantly and positively correlated (all p < 0.05) with IPATM, RPATM, ASAATM
      and PSAATM. To assess the relative strength of these associations, we used non
      nested regression models. There was no significant difference between WC and WHR
      in predicting IPATM and RPATM; WC was a stronger predictor of ASAATM (p < 0.001)
      and PSAATM (p < 0.001) than WHR; WC was also a stronger predictor of IPATM (p =
      0.042) and RPATM (p = 0.045) than BMI, but the relative strengths of WC and BMI
      in predicting ASSATM and PSAATM did not different significantly (p > 0.05); there
      was no significant difference between BMI and WHR in predicting IPATM and RPATM
      (p>0.05), but BMI was a stronger predictor of ASAATM (p = 0.036) and PSAATM (p <
      0.001) than WHR. DISCUSSION: In men WC is the anthropometric index that most
      uniformly predicts the distribution of adipose tissue among several fat
      compartments in the abdominal region, there apparently being little value in
      measuring WHR or BMI.

PMID- 12788964
TI  - Should we add screening for and treating left ventricular hypertrophy to the
      management of all patients needing secondary prevention of cardiovascular
      disease?

PMID- 12788965
TI  - Intracranial plasmacytoma causing acute unilateral loss of vision.

PMID- 12788966
TI  - Assessing chronic fatigue.

PMID- 12788967
TI  - Hashimoto's encephalopathy: clinical, SPECT and neurophysiological data.

PMID- 12788968
TI  - Communication of risks: an analysis beyond numbers.

PMID- 12788969
TI  - The new mapping.

PMID- 12788972
TI  - The complete genome sequence of Mycobacterium bovis.
AB  - Mycobacterium bovis is the causative agent of tuberculosis in a range of animal
      species and man, with worldwide annual losses to agriculture of $3 billion. The
      human burden of tuberculosis caused by the bovine tubercle bacillus is still
      largely unknown. M. bovis was also the progenitor for the M. bovis bacillus
      Calmette-Guerin vaccine strain, the most widely used human vaccine. Here we
      describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its
      comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium
      leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that
      of M. tuberculosis, but deletion of genetic information has led to a reduced
      genome size. Comparison with M. leprae reveals a number of common gene losses,
      suggesting the removal of functional redundancy. Cell wall components and
      secreted proteins show the greatest variation, indicating their potential role in
      host-bacillus interactions or immune evasion. Furthermore, there are no genes
      unique to M. bovis, implying that differential gene expression may be the key to
      the host tropisms of human and bovine bacilli. The genome sequence therefore
      offers major insight on the evolution, host preference, and pathobiology of M.
      bovis.

PMID- 12788971
TI  - A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major
      lupus autoantigen.
AB  - Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen,
      occur in 24-60% of all patients with systemic lupus erythematosus. Anti-Ro
      antibodies are correlated with photosensitivity and cutaneous lesions in these
      patients and with neonatal lupus, a syndrome in which mothers with anti-Ro
      antibodies give birth to children with complete congenital heart block and
      photosensitive skin lesions. In higher eukaryotes, the Ro protein binds small
      RNAs of unknown function known as Y RNAs. Because the Ro protein also binds
      misfolded 5S rRNA precursors, it is proposed to function in a quality-control
      pathway for ribosome biogenesis. Consistent with a role in the recognition or
      repair of intracellular damage, an orthologue of Ro in the radiation-resistant
      eubacterium Deinococcus radiodurans contributes to survival of this bacterium
      after UV irradiation. Here, we show that mice lacking the Ro protein develop an
      autoimmune syndrome characterized by anti-ribosome antibodies, anti-chromatin
      antibodies, and glomerulonephritis. Moreover, in one strain background, Ro-/-
      mice display increased sensitivity to irradiation with UV light. Thus, one
      function of this major human autoantigen may be to protect against autoantibody
      development, possibly by sequestering defective ribonucleoproteins from immune
      surveillance. Furthermore, the finding that mice lacking the Ro protein are
      photosensitive suggests that loss of Ro function could contribute to the
      photosensitivity associated with anti-Ro antibodies in humans.

PMID- 12788973
TI  - Masquerading as self? Endoparasitic Strepsiptera (Insecta) enclose themselves in
      host-derived epidermal bag.
AB  - We report here the case of a metazoan parasite, a strepsipteran, that manipulates
      host epidermal tissue and wraps itself within it; which probably camouflages the
      endoparasite and is recognized as "self" by the host. This mechanism is one of
      immune avoidance among parasitoid insects. The host-derived epidermal "bag" might
      have enabled Strepsiptera to radiate to disparate hosts compared with the
      relatively few taxa (596 species) described so far. They have been recorded as
      parasitizing 34 families belonging to seven orders of Insecta. We also report a
      mechanism of insect ecdysis between the first- and second-instar larva, while
      enclosed in the bag.

PMID- 12788974
TI  - Physical interaction between RRS1-R, a protein conferring resistance to bacterial
      wilt, and PopP2, a type III effector targeted to the plant nucleus.
AB  - RRS1-R confers broad-spectrum resistance to several strains of the causal agent
      of bacterial wilt, Ralstonia solanacearum. Although genetically defined as
      recessive, this R gene encodes a protein whose structure combines the TIR-NBS-LRR
      domains found in several R proteins and a WRKY motif characteristic of some plant
      transcriptional factors and behaves as a dominant gene in transgenic susceptible
      plants. Here we show that PopP2, a R. solanacearum type III effector, which
      belongs to the YopJ/AvrRxv protein family, is the avirulence protein recognized
      by RRS1-R. Furthermore, an interaction between PopP2 and both RRS1-R and RRS1-S,
      present in the resistant Nd-1 and susceptible Col-5 Arabidopsis thaliana
      ecotypes, respectively, was detected by using the yeast split-ubiquitin two
      hybrid system. This interaction, which required the full-length R protein, was
      not observed between the RRS1 proteins and PopP1, another member of the
      YopJ/AvrRxv family present in strain GMI1000 and that confers avirulence in
      Petunia. We further demonstrate that both the Avr protein and the RRS1 proteins
      colocalize in the nucleus and that the nuclear localization of the RRS1 proteins
      are dependent on the presence of PopP2.

PMID- 12788975
TI  - Germ-line transgenesis of the Tc1/mariner superfamily transposon Minos in Ciona
      intestinalis.
AB  - The tadpole larva of the basal chordate Ciona intestinalis has the most
      simplified, basic body-plan of chordates. Because it has a compact genome with a
      complete draft sequence, a large quantity of EST/cDNA information, and a short
      generation time, Ciona is a suitable model for future genetics. We establish here
      a transgenic technique in Ciona that uses the Tc1/mariner superfamily transposon
      Minos. Minos was integrated efficiently into the genome of germ cells and
      transmitted stably to subsequent generations. In addition, an enhancer-trap line
      was obtained. This is a demonstration of efficient, Minos-mediated transgenesis
      in marine invertebrates.

PMID- 12788978
TI  - Chronic T cell-mediated enteropathy in rural west African children: relationship
      with nutritional status and small bowel function.
AB  - Previous studies from The Gambia have shown that poor childhood growth is
      resistant to all but the most intense nutritional intervention and highly
      dependent on small bowel permeability related to enteropathy. We thus aimed to
      characterize the mucosal inflammatory response in rural Gambian children in
      relation to intestinal permeability and nutritional status. Small bowel biopsies
      were taken from 38 rural Gambian children (age, 0.5-3 y) with a range of
      nutritional and clinical states (median weight z score, -4.6; range, 0.5 to 
      6.4), 75% of whom had diarrhea. Morphometry was performed with
      immunohistochemical analysis for a range of lineage and activation markers,
      including proinflammatory and regulatory cytokines, and related to current
      clinical status and gut permeability. Comparison was made with 19 age-matched
      U.K. controls. All Gambian children, regardless of nutritional status, had
      evidence of chronic cell-mediated enteropathy with crypt hyperplasia, villous
      stunting, and high numbers of intraepithelial lymphocytes. CD25+ cells were 20
      fold higher than in U.K. controls. Although small bowel architecture was
      independent of nutritional status, T cell numbers rose and B cell numbers fell
      with worsening nutrition, and mucosal cytokine production became biased toward a
      proinflammatory response, with progressive decrease of transforming growth factor
      beta expression. Tropical enteropathy predates the onset of marasmus and is
      characterized by a cell-mediated TH1 response. Protein-energy malnutrition is
      associated with reduction of regulatory immune responses in the mucosal
      microenvironment, potentially impairing the mechanisms of oral tolerance.

PMID- 12788977
TI  - Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model
      of prostate cancer bone metastasis.
AB  - Emerging evidence indicates that tumor-associated proteolytic remodeling of bone
      matrix may underlie the capacity of tumor cells to colonize and survive in the
      bone microenvironment. Of particular importance, urokinase-type plasminogen
      activator (uPA) has been shown to correlate with human prostate cancer (PC)
      metastasis. The importance of this protease may be related to its ability to
      initiate a proteolytic cascade, leading to the activation of multiple proteases
      and growth factors. Previously, we showed that maspin, a serine protease
      inhibitor, specifically inhibits PC-associated uPA and PC cell invasion and
      motility in vitro. In this article, we showed that maspin-expressing transfectant
      cells derived from PC cell line DU145 were inhibited in in vitro extracellular
      matrix and collagen degradation assays. To test the effect of tumor-associated
      maspin on PC-induced bone matrix remodeling and tumor growth, we injected the
      maspin-transfected DU145 cells into human fetal bone fragments, which were
      previously implanted in immunodeficient mice. These studies showed that maspin
      expression decreased tumor growth, reduced osteolysis, and decreased
      angiogenesis. Furthermore, the maspin-expressing tumors contained significant
      fibrosis and collagen staining, and exhibited a more glandular organization.
      These data represent evidence that maspin inhibits PC-induced bone matrix
      remodeling and induces PC glandular redifferentiation. These results support our
      current working hypothesis that maspin exerts its tumor suppressive role, at
      least in part, by blocking the pericellular uPA system and suggest that maspin
      may offer an opportunity to improve therapeutic intervention of bone metastasis.

PMID- 12788979
TI  - Maternal protein restriction increases hepatic glycogen storage in young rats.
AB  - This study aimed to determine whether maternal protein restriction alters hepatic
      glycogen metabolism. Mated female rats were fed diets containing 20% protein
      throughout pregnancy and lactation (CONT), 8% protein throughout pregnancy and
      lactation (LP), or 8% protein during the last week of pregnancy only and
      lactation (LLP). Weights and lengths were reduced in the LLP and LP offspring
      compared with the CONT offspring. The LLP and LP offspring demonstrated reduced
      insulin concentrations at both 10 and 26 d and also failed to show the increase
      in insulin seen with time in the CONT offspring. Serum glucose and leptin levels
      increased with time but were not different among the groups; however, in relation
      to adiposity leptin levels were greater in the LLP and LP offspring at 26 d. The
      LLP and LP offspring had increased hepatic glycogen at day 10 (CONT, 75.1 +/-
      9.8; LLP, 103.4 +/- 11.0; LP, 116.0 +/- 18.4 glucose residues/g tissue) and d 26
      (CONT, 183.1 +/- 38.9; LLP, 395.3 +/- 16.8; LP, 396.6 +/- 15.1 glucose residues/g
      tissue). Glycogen synthase expression was increased in the LLP and LP offspring
      at 10 d but not 26 d; glucose transporter 2 and glycogen phosphorylase
      expressions were not different at either time. At 26 d glycogen synthase activity
      was not different; however, glycogen phosphorylase a activity was reduced. The
      enhanced capacity to store glycogen despite reductions in insulin secretion
      suggests increased insulin sensitivity possibly acting with an alternative non
      insulin-dependent glycogen storage mechanism.

PMID- 12788980
TI  - Interleukin-10 inhibits proinflammatory chemokine release by neutrophils of the
      newborn without suppression of nuclear factor-kappa B.
AB  - An increase in polymorphonuclear leukocytes (PMNs) and proinflammatory
      chemokines, such as IL-8 and macrophage inflammatory protein-1 alpha (MIP), are
      found in the airways during early stages of bronchopulmonary dysplasia. We
      determined whether IL-10 produces a dose-related inhibition of proinflammatory
      chemokine release from stimulated neutrophils of the newborn and whether the
      mechanism involves the pivotal transcription factor, nuclear factor-kappa B. PMNs
      isolated from the cord blood of healthy newborns were stimulated submaximally
      with either lipopolysaccharide (n = 5) or tumor necrosis factor (n = 4), with and
      without IL-10 (0.01-1000 ng/mL). IL-8 and MIP release were measured in cell
      culture supernatants at 18 h. The presence or absence of nuclear factor-kappa B
      activity and inhibitor-kappa B alpha degradation was measured at 30 min and 3 h
      after PMN stimulation began. During lipopolysaccharide stimulation, IL-10
      significantly reduced IL-8 levels from 50 +/- 16 ng/mL to 7 +/- 3 ng/mL, and MIP
      levels from 14 +/- 5 to 0.7 +/- 0.1 ng/mL (mean +/- SEM, p < 0.01). IL-10
      produced an insignificant reduction in IL-8 and MIP levels after stimulation of
      PMNs with tumor necrosis factor. IL-10 did not inhibit nuclear factor-kappa B
      activation and inhibitor-kappa B alpha degradation in PMNs stimulated with tumor
      necrosis factor or lipopolysaccharide for 30 min. After PMN stimulation for 3 h,
      inhibitor-kappa B alpha cytoplasmic levels were restored; however, they were
      unaffected by IL-10. We conclude that IL-10 is a potent inhibitor of
      lipopolysaccharide-stimulated release of IL-8 and MIP from neutrophils of the
      newborn via a mechanism not involving nuclear factor-kappa B activity. Further
      work is needed to determine whether exogenous IL-10 may be useful for suppressing
      inflammation in bronchopulmonary dysplasia.

PMID- 12788981
TI  - Role of superoxide anion on basal and stimulated nitric oxide activity in
      neonatal piglet pulmonary vessels.
AB  - The superoxide anion (O2*-) appears to be an important modulator of nitric oxide
      bioavailability. Enzymatic scavenging of O2*- is carried out by superoxide
      dismutase (SOD). The present study was designed to characterize the developmental
      changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2)
      several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed
      age-related changes on pulmonary SOD activity and vascular O2*- levels. SOD (1
      300 U/mL) produced endothelium-dependent relaxation of U46619-contracted
      intrapulmonary arteries (fourth branch) and veins from 12- to 24-h-old and 2-wk
      old piglets. SOD-induced relaxation was greater in pulmonary arteries and was
      abolished by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl
      ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in
      the 12- to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced
      relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by
      diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in
      pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity
      in lung tissue did not change with postnatal age. With the use of
      dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find
      significant age- or vessel-related differences in O2*- presence. From the
      putative SOD mimetics tested, only the metal salts MnCl2 and CuSO4 reproduced the
      vascular effects of SOD. In summary, SOD produces endothelium-dependent pulmonary
      vascular relaxation by protecting nitric oxide from destruction by O2*-. This
      effect was less marked in newborns than in 2-wk-old piglets. In contrast,
      pulmonary arteries from newborn piglets are more sensitive to the inhibition of
      endogenous SOD.

PMID- 12788982
TI  - Intestinal adherent bacteria and bacterial translocation in breast-fed and
      formula-fed rats in relation to susceptibility to infection.
AB  - The barrier function of the intestinal mucosa is immature in the newborn mammal,
      and is strengthened by breast milk. We investigated this effect of breast milk by
      comparing the susceptibility to infection assessed in terms of adherent bacterial
      colonization of the intestinal tissue (AdC) and bacterial translocation (BT)
      between breast-fed and formula-fed newborn rats. Three-day-old rat pups were
      assigned to one of three groups: mother-reared (MR), pseudo-cannulated (sham),
      and artificially reared (AR). AR rats were infused with formula through an
      intragastric cannula, under the control of a computer-regulated pumping machine.
      MR and sham rat pups were reared with their respective dams and received breast
      milk until weaning in a specially designed cage. In 10-d-old rats, there was no
      significant difference in the fecal or cecal flora between the AR and MR groups,
      whereas the AdC and the BT to the liver were greater in the AR than MR group.
      Enterobacteriaceae, Streptococcus and/or Enterococcus, and Staphylococcus were
      dominantly detected as microorganisms in AdC flora and BT. The AdC flora did not
      directly reflect the bacterial colonization flora. These findings suggest that AR
      rat pups mature normally, although there is a greater colonization of
      Enterobacteriaceae and BT in AR than MR pups. Consequently, the intestinal
      barrier function of the pups reared by artificial feeding may become susceptible
      to BT, and AdC may be more indicative than bacterial colonization of the
      susceptibility to BT.

PMID- 12788983
TI  - Could monoamine plasma levels and erythrocyte membrane ATPase activities at birth
      be predictive for future hand performance?
AB  - The monoamine and intracellular calcium systems are two major elements of nervous
      system functions. However, their role in human brain development is unclear. We
      studied the association between activity of monoamine and intracellular calcium
      systems during prenatal life and subsequent psychomotor performances in healthy
      children. We used prospective data from 247 children followed from birth through
      6 y of age. Among those, 195 were examined at 9 mo using the Brunet-Lezine
      Scales, whereas 126 were examined at 3 y and 100 at 6 y using the McCarthy Scales
      of Children's Ability. A blood sample was collected from the umbilical cord to
      measure levels of dopamine and serotonin metabolites (homovanillic acid and 5
      hydroxyindoleacetic acid, respectively) and ATPase activities (Na+K+-ATPase and
      Ca2+Mg2+-ATPase). The hand skill score at 6 y of age was significantly and
      negatively correlated with ATPase activities and with monoamine metabolite
      concentrations. No other cognitive score was related to biochemical measures at
      birth. Results were adjusted for child's sex, mother's educational level,
      duration of labor, and tea consumption. Composite scores of ATPase activities and
      monoamine metabolite concentrations measured at birth explained 29% of hand skill
      score variance at 6 y. Our results demonstrate the importance of prenatal factors
      on monoaminergic and ATPase activities in early human psychomotor development.
      This study also suggests that specific psychometric measures such as fine motor
      tests may be a better developmental measurement to correlate with biochemical
      factors than general cognitive scales.

PMID- 12788984
TI  - The role of endothelin converting enzyme inhibition during group B streptococcus
      induced pulmonary hypertension in newborn piglets.
AB  - An endothelin-converting enzyme mediates the conversion from low-potency pro
      endothelin to potent endothelin-1 (ET-1). Increased ET-1 levels have been
      observed in pulmonary hypertension of various etiologies in infants. We
      hypothesized that increased ET-1 levels induce pulmonary hypertension during
      group B Streptococcus (GBS) infusion, and this can be attenuated by the
      administration of an endothelin-converting enzyme inhibitor (ECEI). Twenty-two
      unanesthetized, chronically instrumented newborn piglets received a continuous
      infusion of GBS (3.5 x 10(8) colony-forming units/kg/min) while exposed to 100%
      O2. They were randomly assigned to receive a placebo (PL) or an ECEI
      (phosphoramidon, 30 mg/kg i.v.) 15 min after sustained pulmonary hypertension.
      Comparison of hemodynamic measurements and arterial blood gases at baseline and
      over the first 210 min from the onset of pulmonary hypertension was performed
      between groups. GBS infusion caused significant increases in mean pulmonary
      artery pressure, pulmonary vascular resistance (PVR), systemic vascular
      resistance (SVR), and PVR/SVR, and significant decreases in cardiac output, pH,
      and base excess. After the administration of ECEI, a significant reduction in
      pulmonary artery pressure (p < 0.0001), PVR (p < 0.001), and PVR/SVR (p < 0.01)
      and an improvement in cardiac output (p < 0.01) were observed during GBS
      infusion. The decrease in pH (p < 0.001) and base excess (p < 0.001) during GBS
      infusion was less marked after the administration of ECEI compared with the PL.
      Plasma ET-1 levels were obtained in 20 additional piglets; levels were
      significantly lower in the ECEI compared with PL after 3 h of GBS infusion (p <
      0.02). All animals in the ECEI group survived the study period as opposed to 25%
      survival in the PL group (p < 0.001). These data suggest that the increased
      circulating ET-1 levels mediate, in part, the GBS-induced pulmonary hypertension.

PMID- 12788985
TI  - Renal effects of adenosine A1-receptor blockade with 8-cyclopentyl-1,3
      dipropylxanthine in hypoxemic newborn rabbits.
AB  - The key role of intrarenal adenosine in mediating the hypoxemic acute renal
      insufficiency in newborn rabbits has been well demonstrated using the nonspecific
      adenosine antagonist theophylline. The present study was designed to define the
      role of adenosine A1 receptors during systemic hypoxemia by using the specific A1
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function
      parameters were assessed in 31 anesthetized and mechanically ventilated newborn
      rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis
      (+44%) and GFR (+19%), despite a significant decrease in renal blood flow (RBF) (
      22%) and an increase in renal vascular resistance (RVR) (+37%). In hypoxemic
      conditions, diuresis (-19%), GFR (-26%), and RBF (-35%) were decreased, whereas
      RVR increased (+33%). DPCPX administration hindered the hypoxemia-induced
      decrease in GFR and diuresis. However, RBF was still significantly decreased (
      27%), whereas RVR increased (+22%). In all groups, the filtration fraction
      increased significantly. The overall results support the hypothesis that, in
      physiologic conditions, intrarenal adenosine plays a key role in regulating
      glomerular filtration in the neonatal period through preferential A1-mediated
      afferent vasoconstriction. During a hypoxemic stress, the A1-specific antagonist
      DPCPX only partially prevented the hypoxemia-induced changes, as illustrated by
      the elevated RVR and drop in RBF. These findings imply that the contribution of
      intrarenal adenosine to the acute adverse effects of hypoxemia might not be
      solely mediated via the A1 receptor.

PMID- 12788976
TI  - End-sequence profiling: sequence-based analysis of aberrant genomes.
AB  - Genome rearrangements are important in evolution, cancer, and other diseases.
      Precise mapping of the rearrangements is essential for identification of the
      involved genes, and many techniques have been developed for this purpose. We show
      here that end-sequence profiling (ESP) is particularly well suited to this
      purpose. ESP is accomplished by constructing a bacterial artificial chromosome
      (BAC) library from a test genome, measuring BAC end sequences, and mapping end
      sequence pairs onto the normal genome sequence. Plots of BAC end-sequences
      density identify copy number abnormalities at high resolution. BACs spanning
      structural aberrations have end pairs that map abnormally far apart on the normal
      genome sequence. These pairs can then be sequenced to determine the involved
      genes and breakpoint sequences. ESP analysis of the breast cancer cell line MCF-7
      demonstrated its utility for analysis of complex genomes. End sequencing of
      approximately 8,000 clones (0.37-fold haploid genome clonal coverage) produced a
      comprehensive genome copy number map of the MCF-7 genome at better than 300-kb
      resolution and identified 381 genome breakpoints, a subset of which was verified
      by fluorescence in situ hybridization mapping and sequencing.

PMID- 12788986
TI  - Development of the intestinal bacterial composition in hospitalized preterm
      infants in comparison with breast-fed, full-term infants.
AB  - The establishment and succession of bacterial communities in hospitalized preterm
      infants has not been extensively studied. Because earlier studies depended on
      classical cultural techniques, their results were limited. This study monitored
      the establishment and succession of the neonatal microbiota in the first weeks of
      life by analyzing the 16S rDNA variety in fecal samples applying PCR-denaturing
      gradient gel electrophoresis (PCR-DGGE). Fecal samples from 29 preterm infants
      hospitalized in a neonatal intensive care unit, including samples from antibiotic
      treated infants and one with neonatal necrotizing enterocolitis, were subjected
      to PCR-DGGE analysis. Daily DGGE profiles from all preterm infants during the
      first 4 wk were obtained and analyzed. In addition, feces of 15 breast-fed, full
      term infants and a variety of clinical bacterial isolates were examined and
      compared with the PCR-DGGE profiles of the preterm infants. During the first days
      of life, the DGGE profiles were rather simple but increased in their complexity
      over time. It became obvious that not only the intraindividual band-pattern
      similarity increased over time, but also the interindividual. During the
      observation period, similarity values (Cs) increased in each preterm infant from
      0 to 80%, whereas interindividual Cs increased from 18.1 to 57.4%, revealing the
      acquisition of a highly similar bacterial community in these infants. In
      contrast, Cs-values obtained for breast-fed, full-term infants were rather low
      (11.2%). Escherichia coli, Enterococcus sp., and Klebsiella pneumoniae were the
      bacteria most commonly found in all preterm infants. The interindividual
      bacterial composition in hospitalized preterm infants is more similar in
      comparison with breast-fed, full-term infants and is not necessarily influenced
      by birth weight, diet, or antibiotic treatment.

PMID- 12788987
TI  - The effect of inhaled nitric oxide and oxygen on the hydroxylation of salicylate
      in rat lungs.
AB  - Inhaled nitric oxide (iNO) is used as a selective pulmonary vasodilator, and
      often under conditions when a high fraction of inspired oxygen is indicated.
      However, little is known about the potential toxicity of iNO therapy with or
      without concomitant oxygen therapy. NO can combine with superoxide (O2-) to form
      peroxynitrite (ONOO-), which can in turn decompose to form hydroxyl radical
      (OH.). Both OH. and ONOO- are involved in various forms of lung injury. To begin
      evaluation of the effect of iNO under either normoxic or hyperoxic conditions on
      OH. and/or ONOO- formation, rats were exposed for 58 h to either 21% O2, 21% O2 +
      10 parts per million (ppm) NO, 21% O2 + 100 ppm NO, 50% O2, 90% O2, 90% O2 + 10
      ppm NO, or 90% O2 + 100 ppm NO. We used a salicylate hydroxylation assay to
      detect the effects of these exposures on lung OH. and/or ONOO- formation measured
      as the appearance of 2,3-dihydroxybenzoic acid (2,3-DHBA). Exposure to 90% O2 and
      90% O2 + 100 ppm NO resulted in significantly (p < 0.05) greater lung wet weight
      (1.99 +/- 0.14 g and 3.14 +/- 0.30 g, respectively) compared with 21% O2 (1.23 +/
      0.01 g). Exposure to 21% O2 + 100 ppm NO led to 2.5 times the control (21% O2
      alone) 2,3 DHBA formation (p < 0.05) and exposure to 90% O2 led to 2.4 times the
      control 2,3-DHBA formation (p < 0.05). However, with exposure to both 90% O2 and
      100 ppm NO, the 2,3-DHBA formation was no greater than the control condition (21%
      O2). Thus, these results indicate that, individually, both the hyperoxia and the
      100 ppm NO led to greater salicylate hydroxylation, but that the combination of
      hyperoxia and 100 ppm NO led to less salicylate hydroxylation than either did
      individually. The production of OH. and/or ONOO- in the lung during iNO therapy
      may depend on the ratio of NO to O2.

PMID- 12788988
TI  - Enhanced expression of interferon regulatory factor-1 in the mucosa of children
      with celiac disease.
AB  - Celiac disease (CD) is an enteropathy characterized by a Th1-type immune response
      to the dietary gluten. The transcriptional mechanisms or factors that control Th1
      cell development in this condition remain to be elucidated. The aim of this study
      was to analyze in CD the expression of interferon (IFN) regulatory factor (IRF)
      1, a transcription factor that regulates the differentiation and function of Th1
      cells. Duodenal biopsies were taken from children with untreated CD and control
      children, and analyzed for IRF-1 by Southern blotting of reverse-transcriptase
      PCR products and Western blotting. IRF-1 DNA-binding activity was assessed by
      electrophoretic shift mobility assay. The effect of gliadin stimulation on IRF-1
      induction was investigated in an ex vivo organ culture of treated CD biopsies.
      Enhanced IRF-1 was seen in untreated CD in comparison with controls. This was
      evident at both the RNA and protein level. Furthermore, untreated CD samples
      exhibited stronger nuclear accumulation and DNA-binding activity of IRF-1 than
      controls. In contrast, IRF-2, a transcriptional repressor that binds the same DNA
      element and competes with IRF-1, was expressed at the same level in nuclear
      proteins extracted from both untreated CD and control patients. In explant
      cultures of treated CD biopsies, gliadin enhanced both IRF-1 RNA and protein.
      This effect was prevented by a neutralizing IFN-gamma antibody. Furthermore,
      stimulation of normal duodenal biopsies with IFN-gamma enhanced IRF-1. These data
      indicate that IRF-1 is a hallmark of the gliadin-mediated inflammation in CD and
      suggest that IFN-gamma/IRF-1 signaling pathway can play a key role in maintaining
      and expanding the local Th1 inflammatory response in this disease.

PMID- 12788989
TI  - Dexamethasone aggravates hippocampal apoptosis and learning deficiency in
      pneumococcal meningitis in infant rats.
AB  - In an infant rat model of pneumococcal meningitis the effect of dexamethasone on
      neuronal injury in the hippocampus and on learning disability after recovery from
      the disease was examined. Treatment with dexamethasone or vehicle was started 18
      h after infection, concomitant with antibiotics. Neuronal apoptosis in the
      hippocampal dentate gyrus 34 h after infection was significantly aggravated by
      dexamethasone treatment compared with vehicle controls (p = 0.02). Three weeks
      after acute pneumococcal meningitis, learning capacity of animals was assessed in
      the Morris water maze. The results showed a significantly impaired learning
      performance of infected animals treated with dexamethasone compared with vehicle
      controls (p = 0.01). Dexamethasone had no effect on hippocampal injury or
      learning in uninfected controls. Thus, dexamethasone as adjuvant therapy
      increased hippocampal cell injury and reduced learning capacity in this model of
      pneumococcal meningitis in infant rats.

PMID- 12788990
TI  - Responding to organ failure in HIV-infected patients.

PMID- 12788991
TI  - The new medical malpractice crisis.

PMID- 12788992
TI  - Regression of microalbuminuria in type 1 diabetes.
AB  - BACKGROUND: In the present study, we aimed to determine the frequency of a
      significant reduction in urinary albumin excretion and factors affecting such
      reduction in patients with type 1 diabetes and microalbuminuria. METHODS: The
      study included 386 patients with persistent microalbuminuria, indicated by
      repeated measurements of urinary albumin excretion (estimated on the basis of
      albumin-to-creatinine ratios) in the range of 30 to 299 microg per minute during
      an initial two-year evaluation period. Subsequent measurements during the next
      six years were grouped into two-year periods, averaged, and analyzed for
      regression of microalbuminuria, which was defined as a 50 percent reduction in
      urinary albumin excretion from one two-year period to the next. RESULTS:
      Regression of microalbuminuria was frequent, with a six-year cumulative incidence
      of 58 percent (95 percent confidence interval, 52 to 64 percent). The use of
      angiotensin-converting-enzyme inhibitors was not associated with the regression
      of microalbuminuria. However, microalbuminuria of short duration, salutary levels
      of glycosylated hemoglobin (less than 8 percent), low systolic blood pressure
      (less than 115 mm Hg), and low levels of both cholesterol and triglycerides (less
      than 198 mg per deciliter [5.12 mmol per liter] and 145 mg per deciliter [1.64
      mmol per liter], respectively) were independently associated with the regression
      of microalbuminuria. Patients with salutary levels of all modifiable factors had
      a hazard ratio for regression of 3.0 (95 percent confidence interval, 1.5 to
      6.0), as compared with patients with no salutary levels of any modifiable factor.
      CONCLUSIONS: Frequent regression of microalbuminuria in patients with type 1
      diabetes indicates that elevated urinary albumin excretion does not imply
      inexorably progressive nephropathy. Identification of the multiple determinants
      of the regression of microalbuminuria has implications for current theories about
      the mechanisms of early diabetic nephropathy.

PMID- 12788994
TI  - Screening newborns for inborn errors of metabolism by tandem mass spectrometry.
AB  - BACKGROUND: The recent development of electrospray tandem mass spectrometry makes
      it possible to screen newborns for many rare inborn errors of metabolism, but the
      efficacy and outcomes of screening remain unknown. We examined the effect of the
      screening of newborns by tandem mass spectrometry on the rates of diagnosis of 31
      disorders. METHODS: We compared the rates of detection of 31 inborn errors
      affecting the metabolism of the urea cycle, amino acids, and organic acids and
      fatty-acid oxidation among 362,000 newborns screened by tandem mass spectrometry
      over a four-year period (April 1998 through March 2002) with the rates in six
      preceding four-year birth cohorts in New South Wales and the Australian Capital
      Territory, Australia, where screening, diagnostic, and clinical services were
      centralized. RESULTS: The overall prevalence of disorders during the periods when
      clinical diagnosis was used did not vary between 1982 and 1998. In the cohort
      screened with tandem mass spectrometry, the prevalence of inborn errors,
      excluding phenylketonuria, was 15.7 per 100,000 births (95 percent confidence
      interval, 11.9 to 20.4), as compared with adjusted rates of 8.6 to 9.5 per
      100,000 births in the four preceding four-year cohorts. Of the 57 cases diagnosed
      after the introduction of newborn screening, 15 were diagnosed clinically; 7 of
      the 15 newborns had a normal result on screening. The rate of detection was
      increased specifically for medium-chain acyl-coenzyme A dehydrogenase deficiency
      (P<0.001) and other disorders of fatty-acid oxidation (P=0.007), as compared with
      the 16-year period before the implementation of neonatal screening for these
      disorders. CONCLUSIONS: More cases of inborn errors of metabolism are diagnosed
      by screening with tandem mass spectrometry than are diagnosed clinically. It is
      not yet clear which patients with disorders diagnosed by such screening would
      have become symptomatic if screening had not been performed.

PMID- 12788993
TI  - Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes
      mellitus.
AB  - BACKGROUND: Cardiovascular disease causes severe morbidity and mortality in type
      1 diabetes, although the specific risk factors and whether chronic hyperglycemia
      has a role are unknown. We examined the progression of carotid intima-media
      thickness, a measure of atherosclerosis, in a population with type 1 diabetes.
      METHODS: As part of the Epidemiology of Diabetes Interventions and Complications
      (EDIC) study, the long-term follow-up of the Diabetes Control and Complications
      Trial (DCCT), 1229 patients with type 1 diabetes underwent B-mode ultrasonography
      of the internal and common carotid arteries in 1994-1996 and again in 1998-2000.
      We assessed the intima-media thickness in 611 subjects who had been randomly
      assigned to receive conventional diabetes treatment during the DCCT and in 618
      who had been assigned to receive intensive diabetes treatment. RESULTS: At year 1
      of the EDIC study, the carotid intima-media thickness was similar to that in an
      age- and sex-matched nondiabetic population. After six years, the intima-media
      thickness was significantly greater in the diabetic patients than in the
      controls. The mean progression of the intima-media thickness was significantly
      less in the group that had received intensive therapy during the DCCT than in the
      group that had received conventional therapy (progression of the intima-media
      thickness of the common carotid artery, 0.032 vs. 0.046 mm; P=0.01; and
      progression of the combined intima-media thickness of the common and internal
      carotid arteries, -0.155 vs. 0.007; P=0.02) after adjustment for other risk
      factors. Progression of carotid intima-media thickness was associated with age,
      and the EDIC base-line systolic blood pressure, smoking, the ratio of low-density
      lipoprotein to high-density lipoprotein cholesterol, and urinary albumin
      excretion rate and with the mean glycosylated hemoglobin value during the mean
      duration (6.5 years) of the DCCT. CONCLUSIONS: Intensive therapy during the DCCT
      resulted in decreased progression of intima-media thickness six years after the
      end of the trial.

PMID- 12788995
TI  - Puberty and genetic susceptibility to breast cancer in a case-control study in
      twins.
AB  - BACKGROUND: Breast cancer is thought to result from excessive cumulative exposure
      to ovarian hormones. Different predictors of hereditary and sporadic breast
      cancer suggest different pathogenic mechanisms. Affected twin pairs may help to
      illustrate such differences. METHODS: We obtained information from 1811 pairs of
      female twins, one or both of whom had breast cancer. The pairs were stratified
      according to concordance or discordance for breast cancer, zygosity, the presence
      or absence of a family history of breast cancer, and the presence of bilateral or
      unilateral disease. Disease-concordant monozygotic pairs were assumed to have a
      higher genetic susceptibility than other subgroups of pairs. Paired twins were
      compared with respect to age at puberty and other factors. We calculated adjusted
      odds ratios for the diagnosis of breast cancer when only one twin was affected
      and for the first of the two diagnoses when both were affected. RESULTS: Within
      disease-discordant monozygotic pairs, the twin with an earlier onset of puberty
      did not have an increased risk of breast cancer (adjusted odds ratio, 0.8; 95
      percent confidence interval, 0.6 to 1.2). Within disease-concordant monozygotic
      pairs, the twin with earlier puberty was much more likely to receive the
      diagnosis first (adjusted odds ratio, 5.4; 95 percent confidence interval, 2.0 to
      14.5). In contrast, a later first pregnancy, lower parity, and later menopause
      within the pair were associated with an increased risk of breast cancer when one
      twin was affected but did not predict an earlier diagnosis when both were
      affected. CONCLUSIONS: Within the most genetically susceptible subgroup of twin
      pairs, the strong influence of earlier puberty on the age at the diagnosis of
      breast cancer and the absence of linkage to hormonal milestones later in life
      suggest that most cases of hereditary breast cancer are not related to cumulative
      hormone exposure and that they may instead result from an unusual sensitivity to
      pubertal hormones. Associations between breast cancer and early menarche and
      those with reproductive milestones in adulthood may reflect different genotypes.

PMID- 12788997
TI  - Images in clinical medicine. Emphysematous cholecystitis.

PMID- 12788996
TI  - Successful cardiac transplantation in an HIV-1-infected patient with advanced
      disease.

PMID- 12788998
TI  - Clinical practice. Microscopic hematuria.

PMID- 12788999
TI  - Breast and ovarian cancer.

PMID- 12789000
TI  - Albuminuria and vascular damage--the vicious twins.

PMID- 12789001
TI  - Genes, hormones, and pathways to breast cancer.

PMID- 12789003
TI  - Ventricular ectopy after exercise as a predictor of death.

PMID- 12789002
TI  - Neuronal regeneration after stroke.

PMID- 12789004
TI  - Carcinoid heart disease.

PMID- 12789005
TI  - Genetics of colorectal cancer.

PMID- 12789006
TI  - Vestibular neuritis.

PMID- 12789007
TI  - The electrocardiogram in acute myocardial infarction.

PMID- 12789008
TI  - Postmenopausal hormone therapy.

PMID- 12789009
TI  - Elective primary cesarean delivery.

PMID- 12789011
TI  - Zygotic-splitting rates after single-embryo transfers in in vitro fertilization.

PMID- 12789010
TI  - Computer crash.

PMID- 12789012
TI  - Images in clinical medicine. Cardiac tamponade in Dressler's syndrome.

PMID- 12789014
TI  - Dendritic initiation and propagation of spikes and spike bursts in a multimodal
      sensory interneuron: the crustacean parasol cell.
AB  - Invasion of dendrites by spikes and spike bursts can play a critical role in
      regulating the output of central neurons by modifying their dynamic input-output
      relationships. Back-propagating bursts can modulate voltage-gated channels in the
      short term and can also modify long-term responses to synaptic input. Determining
      the morphological site of spike initiation and the mode of propagation through
      the dendritic arbor is therefore crucial to an understanding of a neuron's
      functional properties. I used electrophysiological methods to study parasol cells
      in isolated, perfused head preparations of the freshwater crayfish Procambarus
      clarkii to determine the compartment of origin of orthodromically activated
      action potentials and bursts that propagate within the dendritic arbor and to
      examine the identity of low-amplitude, electrotonically recorded spike events
      that are present in more than one-half of the intracellular recordings obtained
      from dendrites in these neurons. Experiments using antidromic activation of
      parasol cell axons indicated that electrotonically recorded spikes probably are
      generated in neighboring parasol cells, to which the impaled neurons are
      electrically coupled. Both paired intracellular recordings and extracellular
      field potential measurements were used to compare arrival times of antidromic and
      orthodromic spikes at loci in the vicinity of the trunk and the basal branch
      compartments of parasol cell dendrites. These methods provided consistent
      results, indicating that synaptically evoked action potentials are initiated at a
      site on the trunk, from which point they back-propagate into the basal branches
      within the hemiellipsoid body, and presumably, also orthodromically to the axon.
      Data are presented suggesting that bursts also arise at a trunk locus, but one
      that is different from the initiation point of single spikes evoked by excitatory
      postsynaptic potentials (EPSPs). Morphological specializations between the
      dendritic trunk and basal branches may facilitate back-propagation of spikes and
      spike bursts into the basal branches.

PMID- 12789015
TI  - Spreading depression can be elicited in brain stem of immature but not adult
      rats.
AB  - Spreading depression (SD), a neuronal mechanism involved in brain
      pathophysiology, occurs in brain areas with high neuronal density such as the
      cerebral cortex. By contrast, the brain stem is thought to be resistant to SD.
      Here we show that DC shifts resembling cortical SD can be elicited in rat brain
      stem by topical application of KCl but not by pricking the brain stem. However,
      this was only possible until postnatal day 13, and, in addition, susceptibility
      for SD had to be enhanced. The latter was achieved by superfusion of the brain
      stem for 45 min with a solution containing acetate instead of chloride ions.
      Transient asphyxia or hypoxia by 2 min breathing 6% O2 in N2 had a similar
      effect. Negative brain stem DC deflections were paralleled by an increase of
      extracellular potassium concentration </=40 mM and were spreading, but unlike
      cortical SD they were not inducible by glutamate and N-methyl-d-aspartate (NMDA).
      Time course and slope of brain stem SD either resembled cortical SD or were long
      lasting and sustained. The latter stopped normal breathing. Different from
      cortical SD, negative brain stem DC deflections were changed in their slope
      (mostly converted into sustained shape, peak time was significantly prolonged,
      decline-time and duration were prolonged), but not abolished by the NMDA receptor
      blocker MK-801. Thus we demonstrate that the immature brain stem has the capacity
      to generate negative DC shifts, which could be relevant as a risk factor in
      newborn brain stem function.

PMID- 12789013
TI  - Dissociating cortical regions activated by semantic and phonological tasks: a
      FMRI study in blind and sighted people.
AB  - Previous neuroimaging studies of language processing in blind individuals
      described cortical activation of primary (V1) and higher tier visual areas,
      irrespective of the age of blindness onset. Specifically, participants were given
      nouns and asked to generate an associated verb. These results confirmed the
      presence of adaptations in the visual cortex of blind people and suggested that
      these responses represented linguistic operations. The present functional
      magnetic resonance imaging study attempted to further characterize these
      responses as being preferential for semantic or phonological processing. Three
      groups of participants (sighted, early onset, and late-onset blind) heard lists
      of related words and attended to either a common meaning (semantic task) or
      common rhyme (phonological task) that linked the words. In all three groups, the
      semantic task elicited stronger activity in the left anterior inferior frontal
      gyrus and the phonological task evoked stronger activity bilaterally in the
      inferior parietal cortex and posterior aspects of the left inferior frontal
      gyrus. Only blind individuals showed activity in occipital, temporal, and
      parietal components of visual cortex. The spatial extent of visual cortex
      activity was greatest in early blind, who exhibited activation in all ventral and
      dorsal visual cortex subdivisions (V1 through MT) for both tasks. Preferential
      activation appeared for the semantic task. Late blind individuals exhibited
      responses in ventral and dorsal V1, ventral V2, VP and V8, but only for the
      semantic task. Our findings support prior evidence of visual cortex activity in
      blind people engaged in auditory language processing and suggest that this
      activity may be related to semantic processing.

PMID- 12789016
TI  - Stretch sensitivity of cutaneous RA mechanoreceptors in rat hairy skin.
AB  - Twenty-five rapidly adapting mechanoreceptor afferents were recorded in an in
      vitro preparation of rat skin and nerve. Single units were recorded while the
      skin was subjected to dynamic uniaxial stretch using a pseudo-Gaussian noise
      (PGN) input waveform. Force was the controlled variable in stretch stimuli.
      Measured loads and displacements were used to calculate tensile stresses,
      strains, and their rates of change. Associations between spike responses and
      individual stimulus components such as tensile stress or strain were determined
      in a reverse correlation design using multiple logistic regression. Spikes were
      strongly associated with stress, at memory times from 0 to 14 ms, and with the
      rate of change of stress, at a memory times between 6 and 18 ms. There was a
      strong interaction between stress and its rate of change, with a maximum value at
      a memory time of 10 ms. We found no relationship between spike responses and
      strain.

PMID- 12789017
TI  - Possible roles of kainate receptors on GABAergic nerve terminals projecting to
      rat substantia nigra dopaminergic neurons.
AB  - GABAergic afferent inputs are thought to play an important role in the control of
      the firing pattern of substantia nigra pars compacta (SNc) dopaminergic neurons.
      We report here the actions of presynaptic kainite (KA) receptors in GABAergic
      transmission of rat SNc dopaminergic neurons. In mechanically dissociated rat SNc
      dopaminergic neurons attached with native presynaptic nerve terminals, GABAergic
      miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of
      conventional whole cell patch recording mode. In the voltage-clamp condition, KA
      (3 microM) significantly increased GABAergic mIPSC frequency without affecting
      the current amplitude. This facilitatory effect of KA was not affected in the
      presence of 20 microM GYKI52466, a selective AMPA receptor antagonist, but was
      completely inhibited in the presence of 20 microM CNQX, an AMPA/KA receptor
      antagonist. Presynaptic KA receptors on GABAergic terminals were mainly permeable
      to Na+ but impermeable to Ca2+ because KA-induced facilitation of mIPSC frequency
      was completely suppressed in either Na+-free or Ca2+-free external solutions, and
      in the presence of 200 microM Cd2+, a general voltage-dependent Ca2+ channel
      blocker. In the slice preparation, KA increased GABAergic spontaneous mIPSC
      frequency, but significantly suppressed evoked IPSC (eIPSC) amplitude. However,
      this inhibitory action on eIPSCs was reversed by 10 microM CGP55845, a selective
      GABAB receptor antagonist, implicating the possible involvement of GABAB
      autoreceptors in KA-induced modulation of GABAergic transmission. Thus
      presynaptic KA receptors on GABAergic nerve terminals synapsing onto SNc neurons
      may play functional roles contributing the fine control of neuronal excitability
      and firing pattern of SNc.

PMID- 12789018
TI  - Ethical issues concerning animal research outside the laboratory.
AB  - Unique ethical issues can be associated with research outside the customary
      laboratory setting. Protocols involving wild animals must consider that any
      infringement on the wild nature of the species can be disruptive and may involve
      pain, fear, anxiety, and frustration, all of which constitute ethical harm that
      must be balanced with anticipated benefit. Agricultural and companion animal
      research, however, take place in a human-engineered environment and involves
      domesticated species adapted to human contact. Special animal welfare issues can
      be related to agricultural production goals that fail to deal adequately with
      moral concerns. Human/companion animal relationships, on the other hand, present
      unique moral obligations to animal owners. Other factors may present additional
      ethical issues when research is performed outside the laboratory. These factors
      include a required sensitivity to the environment of wild animals and an
      awareness that this outside research may to quite public and, therefore,
      vulnerable to community perception. The institutional animal care and use
      committee(IACUC) has the responsibility to ensure that research in outside
      settings is ethical and properly implemented. This responsibility requires that
      IACUC members have knowledge of the needs of a wide range of species and that a
      process is in place to allow effective monitoring of research in remote
      locations. Finally, and most important, there must be a sensitivity to the unique
      ethical considerations outlined here. Armed with these strengths, the IACUC will
      be effective in what may be unfamiliar surroundings and will have a significant
      opportunity to cause improvements in animal welfare.

PMID- 12789019
TI  - Regulatory issues surrounding the use of companion animals in clinical
      investigations, trials, and studies.
AB  - Laboratory animal veterinarians sometimes encounter animals with rare conditions
      and may subsequently become involved in the performance of related animal
      research outside the laboratory, in homes, in veterinary clinics, or in
      universities to which owners have donated their animals for study. Similarly,
      veterinarians may monitor animal companion vaccination studies, performed to
      optimize preventive health care or minimize physiological variability and
      research confounders associated with a preventive medicine program for dogs and
      cats utilized for research procedures. These nontraditional uses of dogs, cats,
      and other companion animals in research have spurred the establishment of
      regulations to ensure that the animals benefit from clinical veterinary products
      and techniques. Included and described are the 2002 Public Health Service Policy,
      the Animal Welfare Act (AWA), the Federal Food, Drug, and Cosmetic Act, and the
      regulations of the US Department of Agriculture in response to the AWA. The
      complexities of clinical research with companion animals outside standard
      biomedical research facilities are discussed.

PMID- 12789020
TI  - Assessment of pain in dogs: veterinary clinical studies.
AB  - Hundreds of thousands of animals are presented to US veterinarians annually for
      surgery or for evaluation of painful disease. This large population offers the
      opportunity for clinical research of both acute and chronic pain syndromes.
      Although there is growing interest by veterinary clinical specialists to explore
      the nature of animal pain and how best to treat it, this resource is relatively
      unknown to the pain research community. Computer-assisted collection of
      behavioral data has created new opportunities for characterizing the pain
      experience in animal species for the benefit of both animals and humans. This
      review describes the current state of veterinary clinical pain studies in dogs
      and an application of computer-assisted behavioral analysis.

PMID- 12789021
TI  - Agricultural (nonbiomedical) animal research outside the laboratory: a review of
      guidelines for institutional animal care and use committees.
AB  - Challenges and published guidelines associated with appropriate care and use of
      farm animals in agricultural research conducted outside the laboratory are
      briefly reviewed. The Animal Welfare Act (Title 9 of the 2000 Code of Federal
      Regulations), which regulates the care and use of agricultural animals in
      biomedical research, does not include livestock and poultry used in agricultural
      research. Farm animal research funded (and thereby regulated) by the US Public
      Health Service is further discussed in the National Research Council's 1996 Guide
      for the Care and Use of Laboratory Animals. However, neither of these guidelines
      adequately addresses the unique attributes of research and teaching designed to
      improve production agriculture. That information is contained in the Guide for
      the Care and Use of Agricultural Animals in Agricultural Research and Teaching
      (the Ag Guide), published by the Federation of Animal Science Societies in 1999.
      The Ag Guide provides excellent general recommendations for agricultural animal
      research. It serves as an invaluable resource for institutional animal care and
      use committees, which attempt to balance the welfare of farm animals and the
      needs of those working to improve animal agriculture.

PMID- 12789023
TI  - Demands for rhesus monkeys in biomedical research: a workshop report.

PMID- 12789022
TI  - Behavioral evaluation of the psychological welfare and environmental requirements
      of agricultural research animals: theory, measurement, ethics, and practical
      implications.
AB  - The welfare of agricultural research animals relies not only on measures of good
      health but also on the presence of positive emotional states and the absence of
      aversive or unpleasant subjective states such as fear, frustration, or
      association with pain. Although subjective states are not inherently observable,
      their interaction with motivational states can be measured through assessment of
      motivated behavior, which indicates the priority animals place on obtaining or
      avoiding specific environmental stimuli and thus allows conclusions regarding the
      impact of housing, husbandry, and experimental procedures on animal welfare.
      Preference tests and consumer demand models demonstrate that animal choices are
      particularly valuable when integrated with other behavioral and physiological
      measurements. Although descriptive assessments of apparently abnormal behavior
      such as stereotypies and "vacuum behaviors" provide indications of potentially
      impoverished environments, they should be used with some caution in drawing
      welfare conclusions. The development of stereotypies may in some cases be linked
      to psychiatric dysfunction and reflect underlying neurophysiological impairments,
      which have implications for the ability to perform flexible behavior and thus the
      quality of research data provided by this kind of behavioral measurement (e.g.,
      in pharmaceutical research). Environmental modifications, commonly termed
      "enrichment," can have diverse consequences for cognitive function, physiological
      responses, health, psychological welfare, and research data. Simple practical
      modifications of housing, husbandry, and experimental design are suggested to
      improve the psychological welfare of agricultural research animals in accordance
      with the principles of refining, reducing, and replacing (the "3Rs"), which
      underlie US Public Health Service Policy, and prevailing public ethics.

PMID- 12789024
TI  - The effect of suprapubic catheterization versus transurethral catheterization
      after abdominal surgery on urinary tract infection: a randomized controlled
      trial.
AB  - BACKGROUND/AIM: Transurethral catheterization is generally associated with a
      higher incidence of urinary tract infections than suprapubic catheterization;
      however, suprapubic catheterization is associated with other disadvantages such
      as higher costs and a more difficult technique, and at the moment there is no
      consensus about the use of both catheter systems. Therefore, a prospective
      randomized study was performed to investigate the effects of suprapubic
      catheterization and transurethral catheterization in patients undergoing surgery
      on the incidence of urinary tract infections and patient satisfaction. METHODS:
      Patients who underwent an elective laparotomy were randomized and received a
      suprapubic or transurethral catheter. The primary end point was urinary tract
      infection. Other parameters of urinary tract infection, as well as duration of
      catheterization, hospital stay, and number of recatheterizations and of
      relaparotomies were monitored. Treatment 'per protocol' was also analyzed after
      exclusion of patients receiving another catheter than randomized for. Patients
      were asked for their satisfaction with the catheters and complaints during and
      after catheterization. RESULTS: 165 patients were eligible, of whom 19 patients
      had to be excluded. 75 patients were allocated to receive the suprapubic catheter
      and 71 the transurethral catheter. There was no difference in the incidence of a
      urinary tract infection between the suprapubic group (n = 9/75; 12%) and the
      transurethral group (n = 8/71; 11%). Most patients (6/9) who developed a urinary
      tract infection in the suprapubic group, however, underwent recatheterization
      because of postoperative complications/sepsis and relaparotomy. The incidence of
      urinary tract infections in patients who received a suprapubic catheter and not a
      transurethral catheter was 3/59 (5%). The patients did not differ with respect to
      satisfaction and complaints. Being a men, recatheterization and duration of
      catheterization are risk factors. CONCLUSIONS: The incidence of a urinary tract
      infection between a suprapubic catheter and a transurethral catheter in patients
      undergoing major surgery was not different. A potential advantage of the
      suprapubic catheter (reduction of urinary tract infections) is probably partly
      negated, because transurethral catheters were used if recatheterization was
      indicated during the postoperative stay or due to complications.

PMID- 12789025
TI  - Are some cases of infected pancreatic necrosis treatable without intervention?
AB  - BACKGROUND: Infected pancreatic necrosis is considered an absolute indication for
      interventional management such as percutaneous drainage or surgery. The presence
      of retroperitoneal air is a sign of anaerobic sepsis. METHOD: A retrospective
      review of case records of patients presenting with severe acute pancreatitis and
      pancreatic necrosis was performed to identify cases in whom conservative
      treatment was followed by a satisfactory outcome. RESULTS: Four patients were
      identified over a 3-year period who had pancreatic necrosis and retroperitoneal
      air; they were treated with antibiotics and intensive care, and they improved
      without any interventional treatment. CONCLUSIONS: Some patients with infected
      pancreatic necrosis are treatable medically. The clinical status of the patients
      may well be a more important factor governing the choice of the treatment
      approach than bacteriological findings of infection alone.

PMID- 12789026
TI  - Alveolar echinococcosis in Turkey. Experience from an endemic region.
AB  - BACKGROUND: Radical resection is the only potentially curative treatment for
      hepatic alveolar echinococcosis (AE). Although Turkey is an endemic region,
      population screening is not performed and early diagnosis is rare. Consequently,
      surgeons are compelled to explore possibilities such as near-total resection and
      biliodigestive anastomosis for palliation of jaundice. METHODS: Surgery was
      performed in 32 patients with hepatic AE with the following indications: (1)
      resection; (2) palliation of jaundice; (3) definite assessment of operability;
      (4) failure in the management of cavity infection by percutaneous methods.
      Curative resection (R0 = complete resection of all parasitic mass [n = 9], and R1
      = a resection in which a small remnant was left on a vital structure [n = 8])
      were performed in 17 patients, intrahepatic cholangiojejunostomy in 7, laparotomy
      external drainage in 7, and debulking in 1. RESULTS: Perioperative mortality
      rates were 2/17, 0/7, 2/7 and 1/1, respectively. Twelve patients in the curative
      resection group are alive without recurrence/progression of the small remnant
      during a median follow-up of 59 (range 27-116) months. One patient developed an
      inoperable recurrence that was treated with albendazole. One patient was lost to
      follow-up. Long-term albendazole treatment was effective in all R1 patients
      except a patient who had slow asymptomatic progression. Successful palliation of
      jaundice was achieved in 5 of the 7 intrahepatic cholangiojejunostomy patients.
      CONCLUSIONS: The results of R1 resection in alveolar hydatid disease are similar
      to those of R0 resection; a small remnant is successfully controlled by
      albendazole. In patients with jaundice due to hilar invasion, biliary diversion
      from segment 3 or 5 is effective for palliation of the jaundice and facilitates
      albendazole treatment.

PMID- 12789029
TI  - Personalization as it relates to nurse suffering: how managers can recognize the
      phenomenon and assist suffering nurses.

PMID- 12789027
TI  - Renoprotective effects of omapatrilat are mediated partially by bradykinin.
AB  - AIM: To investigate the effects of omapatrilat on systemic and renal
      hemodynamics, glomerular dynamics, renal function, and histopathological changes
      as well as the participation of the bradykinin B2 receptor in WKY, SHR, and L
      NAME/SHR rats. METHODS: Eight groups of 17-week-old rats were examined using
      renal micropuncture techniques and histopathological analyses after 3 weeks of
      treatment: group 1, WKY control; group 2, WKY+omapatrilat (40 mg/kg/day); group
      3, SHR control; group 4, SHR+omapatrilat; group 5, SHR+L-NAME (50 mg/l); group 6,
      SHR+L-NAME+omapatrilat; group 7, SHR+L-NAME for 3 weeks followed by omapatrilat
      for a subsequent 3 weeks, and group 8, SHR+L-NAME+omapatrilat+bradykinin
      antagonist icatibant (500 microg/kg/day). RESULTS: In WKY and SHR, omapatrilat
      significantly reduced the mean arterial pressure, increased effective renal blood
      flow and single nephron plasma flow associated with reduced glomerular arteriolar
      resistances. Furthermore, omapatrilat prevented and reversed L-NAME induced
      urinary protein excretion, glomerular and arteriolar injuries, glomerular
      morphometric alterations, and glomerular apoptosis (at least, p < 0.05).
      Icatibant partially inhibited these beneficial effects of omapatrilat.
      CONCLUSION: Omapatrilat provided potent antihypertensive and renoprotective
      actions, which were mediated, in part, by bradykinin.

PMID- 12789030
TI  - DHHS's final rule on the Quality Assessment and Performance Improvement Program.
AB  - All facilities that participate in the Medicare and Medicaid programs must comply
      with the Quality Assessment and Performance Improvement Program as a condition of
      participation. Nurse executives need to be familiar with the requirements of this
      program in order to be able to participate in ensuring the compliance of the
      facilities with which they work.

PMID- 12789031
TI  - Promoting a good death for persons with dementia in nursing facilities: family
      caregivers' perspectives.
AB  - The experience of dying from Alzheimer's disease (AD) in a nursing home setting
      is a poorly understood phenomenon. Fifty-seven family member caregivers of
      persons with Alzheimer's disease, who had died as a resident in a national
      nursing home chain, participated in a structured telephone interview. Despite the
      belief that their loved one had died with dignity, 16 out of 57 (28%) family
      member caregivers believed that their loved one had not experienced a good death.
      This article reviews the definition of a good death and the six themes of a good
      death found in the literature: pain and symptom management; clear decision
      making; preparation for death; completion; contributing to others; and
      affirmation of the whole person. Five standards for evaluating the quality of an
      anticipated death are discussed in relation to the experiences of the persons
      with AD. Finally, recommendations for how nurse administrators and other members
      of the healthcare team can promote a positive death experience for a person with
      AD are proposed.

PMID- 12789032
TI  - The unilateral DNR order--one hospital's experience.
AB  - Hospital or institutional policies that guide the activity of nurses in the care
      of their patients may, at times, be controversial. Nursing staffs often act as
      gatekeepers of patient care activities and the implementers of institutional
      policy. When nurses raise questions as to the appropriateness of a given policy
      statement, the institution should take serious notice and, perhaps, even study
      the policy outcomes that relate to the concerns expressed by the nursing staff.
      This article introduces a policy that originally prompted serious concerns by the
      nursing staff at one institution. The nursing staff voiced their concerns
      regarding a revision in the DNR policy that would allow physicians to write
      unilateral do-not-resuscitate (DNR) orders. Because of this, a review of this
      policy took place and the results were used to dispel unfounded concerns and also
      to improve the use of the policy. This article may help nursing administrators to
      understand better the importance of policy-related studies and it may also
      encourage nurses to question policy statements and guidelines that may present
      some concerns. Enhanced patient care will ultimately result by such teamwork and
      scholarly activity.

PMID- 12789033
TI  - Conflict of interest, or interest in conflict?

PMID- 12789034
TI  - Identifying and treating mycotic skin infections.
AB  - PURPOSE: To provide physicians and nurses with an overview of mycotic infections
      and related cutaneous manifestations. TARGET AUDIENCE: This continuing-education
      activity is intended for physicians and nurses with an interest in learning how
      to recognize and treat mycotic skin infections. OBJECTIVES: After reading the
      article and taking the test, the participant will be able to:1. Identify the
      cause and clinical presentation of mycotic skin infections.2. Identify diagnostic
      tests used in evaluating patients with mycotic skin infections.3. Identify
      appropriate treatment options in patients with mycotic skin infections.

PMID- 12789035
TI  - Pressure ulcer prediction in older adults receiving home health care:
      implications for use with the OASIS.
AB  - OBJECTIVE: To determine whether admission data routinely collected on the Outcome
      and Assessment Information Set (OASIS) might be used to identify the older adult
      at risk for pressure ulcer development in home health care. DESIGN: Secondary
      analysis of data from a retrospective cohort study. SETTING AND SUBJECTS: The
      sample included 1711 nonhospice patients 60 years or older and free of pressure
      ulcers who were admitted to the intermittent skilled nursing division of a large
      midwestern home health care agency between January 1995 and March 1996. MAIN
      OUTCOME MEASURES: Data on potential risk factors were extracted from admission
      information. Those identical to items on the admission OASIS assessment were
      included in the study. Patient records were followed forward chronologically to
      either pressure ulcer development or absence. MAIN RESULTS: Cox regression
      analysis showed that limitation in activity to bed, dependence in dressing,
      urinary incontinence, and needing assistance with transferring predicted Stage I
      pressure ulcer development (P </=.001). Bowel/bladder incontinence, oxygen use, a
      current fracture, and dependence in dressing predicted Stage II and greater
      pressure ulcer development (P </=.001). Predictors of Stage I plus Stage II and
      greater pressure ulcers included those predictors from each of the individual
      models, including limitation in activity to bed, dependence in dressing, a
      current fracture, oxygen use, needing assistance with transferring, and urinary
      incontinence (P </=.001). CONCLUSION: These findings suggest that the admission
      OASIS assessment may provide a method for identifying elderly patients who are at
      risk for developing Stage I and Stage II pressure ulcers in home health care.

PMID- 12789036
TI  - Effects of support surface relief pressures on heel skin blood perfusion.
AB  - OBJECTIVE: To investigate the effect of pressure-relief magnitude on heel blood
      flow. DESIGN: 12 healthy subjects (5 male, 7 female; 21 to 43 years of age) lay
      on a support surface for 50 minutes with 1 heel on the end cell of the support
      surface. Cell pressure was computer controlled to vary cyclically at 5-minute
      intervals between a constant 20 mm Hg during loading and 10, 5, and 0 mm Hg
      during off-loading. Heel skin blood perfusion was monitored by laser Doppler
      probes on the heel and foot dorsum. Average skin blood perfusion during each 10
      minute cycle and the hyperemic response after pressure relief were determined
      absolutely and relative to baseline. SETTING: University research center.
      RESULTS: An inverse relationship was found between relief pressure and heel skin
      blood perfusion over each pressurization-relief cycle and during the hyperemia
      phase. Full-cycle average skin blood perfusion associated with release to 0, 5,
      and 10 mm Hg were 34.1 +/- 7.5 arbitrary units (AU), 26.4 +/- 7.5 AU, and 9.3 +/-
      3.3 AU, respectively (P <.001). CONCLUSIONS: The reduced average skin blood
      perfusion is attributable to blunting of hyperemia when relief pressure is too
      high. When it corresponded to an interface pressure near diastolic pressure,
      little, if any, functional pressure relief or hyperemia is realized. Suitable
      relief pressures are likely dependent on an individual's diastolic blood pressure
      and the net tissue forces acting on heel blood vessels. This suggests that lower
      blood pressures need lower pressure-relief levels. It is suspected that if
      depressed vascular responsiveness and/or diminished hyperemic reserve is also
      present, even lower relief pressures are needed.

PMID- 12789037
TI  - Ostomy pearls: a concise guide to stoma siting, pouching systems, patient
      education and more.

PMID- 12789038
TI  - Ostomy Medicare policy 2003.

PMID- 12789040
TI  - Commending the camp.

PMID- 12789041
TI  - Toxic managers at all levels.

PMID- 12789042
TI  - Valuing certification.

PMID- 12789043
TI  - Triumph over toxicity.

PMID- 12789044
TI  - Vaccination available.

PMID- 12789045
TI  - Motivation: your key IC ingredient.
AB  - Positive reinforcement and a sense of self-motivation are important factors in
      helping your staff follow an infection control plan.

PMID- 12789046
TI  - What's in a name? The taxonomy and nomenclature puzzle, part 1.
AB  - Nursing needs a unified, ubiquitous language with which to describe its unique
      contributions to the health care process. The first step to creating this
      language is to understand the terms.

PMID- 12789047
TI  - Positive discipline reaps retention.

PMID- 12789048
TI  - Strategies at work. Innovative programs grab a thumbs up.

PMID- 12789049
TI  - Take the fear out of sentinel events.
AB  - Follow the proper procedure for identifying and reporting sentinel events to the
      Joint Commission to decrease their incidence.

PMID- 12789050
TI  - Make room for patient privacy.
AB  - Sharing patient information is the hallmark of nursing care continuity. Learn how
      HIPAA affects the way nurses practice.

PMID- 12789051
TI  - Ethics committees: guidance through gray areas.
AB  - Review a plan for implementing and maintaining ethics committees.

PMID- 12789052
TI  - Pinpointing intravascular device infections.
AB  - The U.S. Centers for Disease Control and Prevention (CDC) recently revised its
      guidelines for preventing infections related to intravenous infusion devices.
      Review these recommendations and learn how to best comply with them to provide
      safer vascular care.

PMID- 12789053
TI  - Balancing staffing and safety.
AB  - Several high-profile research studies link nurse staffing and patient safety.

PMID- 12789054
TI  - What's your perspective - past, present, or future?
AB  - Time Typing sets up a behavior model for three different perspectives: past,
      present, and future.

PMID- 12789055
TI  - Consider joining a medical fraud team.
AB  - A registered nurse can bring balance to the investigation process of a medical
      fraud team.

PMID- 12789056
TI  - Bradycardia and medications: identify the dangerous pace.
AB  - Review bradycardia and medications that can cause the condition.

PMID- 12789058
TI  - Infection control staff update. SARS and safety.
AB  - The recent SARS outbreak emphasizes the need for employee safety.

PMID- 12789059
TI  - The use of non-invasive ventilation in the emergency department.

PMID- 12789060
TI  - Non-invasive ventilation delivered by conventional interfaces and helmet in the
      emergency department.
AB  - Non-invasive positive pressure ventilation is increasingly used as a first-line
      treatment for respiratory failure. Non-invasive positive pressure ventilation can
      reduce the complications of endotracheal intubation such as barotrauma,
      nosocomial infections and the need for sedation. Non-invasive positive pressure
      ventilation has been shown to reduce the rate of endotracheal intubation in acute
      cardiogenic pulmonary oedema (27%), in chronic obstructive pulmonary disease
      (21%), and in acute respiratory failure (17%). Non-invasive positive pressure
      ventilation can be successfully delivered in the emergency department or in the
      general ward. However, the criteria for interrupting non-invasive positive
      pressure ventilation must be stricter (i.e. failure to improve gas exchange
      within 30 min) than in the general ward. One of the main reasons for the failure
      of non-invasive positive pressure ventilation lies in the technical problems
      caused by the face mask. We recently developed a new interface, the 'helmet', to
      deliver non-invasive positive pressure ventilation. When using the helmet instead
      of a face mask an increase of 10 cm H(2)O of pressure support and a fast
      pressurization rate are recommended. In a lung model and in healthy individuals
      the helmet reduced inspiratory effort. In hypoxemic patients the helmet reduced
      the intubation rate and the incidence of face mask-related complications. We
      believe that the helmet can extend the application of non-invasive positive
      pressure ventilation in different categories of patients with respiratory
      failure.

PMID- 12789062
TI  - How do Belgian mobile intensive care units deal with cardiovascular emergencies?
AB  - OBJECTIVES: To assess the availability and use of diagnostic tools, therapeutic
      equipment and drugs for the prehospital treatment of acute coronary syndromes,
      cardiopulmonary arrest and other cardiovascular emergencies in Belgian physician
      staffed and hospital-based mobile intensive care units. METHODS: In April 2001, a
      questionnaire was sent to all Belgian mobile intensive care unit centres.
      RESULTS: The response rate was 90%. There was a 100% availability of many drugs
      and therapeutic equipment, with a well-established role in the care of
      cardiovascular emergencies: defibrillators, nitrates, epinephrine, atropine and
      diuretics. Important emergency drugs and tools were not ubiquitously available:
      external pacemakers (90%), aspirin (90%), bicarbonate (99%), amiodarone (87%),
      and intravenous beta-blockers (75%). Twelve-lead electrocardiogram recorders and
      thrombolytics had a rather low availability (46 and 20%, respectively) and were
      rarely used. There was a high availability of some drugs with limited data to
      support their use: oral calcium antagonists (61%), bretylium (65%) and
      isoproterenol (92%). CONCLUSIONS: In Belgian mobile intensive care units the
      availability and use of technical and diagnostic equipment and cardiac drugs
      varied to an important extent. A local multidisciplinary evaluation may improve
      prehospital cardiovascular care by implementing current guidelines.

PMID- 12789061
TI  - 'Boussignac' continuous positive airway pressure system: practical use in a
      prehospital medical care unit.
AB  - Continuous positive airway pressure in acute cardiogenic pulmonary edema is
      rarely used by prehospital emergency care units, because of the particular
      technical drawbacks of existing equipment. The aim of this one year prospective
      descriptive open study without a control group was to assess the technical
      feasibility of using the Boussignac continuous positive airway pressure system
      (Vygon) in a prehospital medical care service. Statistical comparisons were
      performed using Student's t-test or a Wilcoxon T-test. There were 57 decisions to
      use continuous positive airway pressure. Seven records were excluded. Four
      patients were intubated on the scene and six within one hour after hospital
      admission. The respiratory rate and transcutaneous oxygen saturation improved
      significantly for all of the other patients (Student's t-test P < 0.001). The
      Boussignac continuous positive airway pressure system has many advantages,
      including flexibility and pressure monitoring, lower oxygen consumption, and ease
      of use. These should allow this technique to be used more widely by prehospital
      teams.

PMID- 12789063
TI  - Children with attention deficit hyperactivity disorder and attendance at
      hospital.
AB  - The aim of this study was to identify the risk of injury for children with
      attention deficit hyperactivity disorder. Children with attention deficit
      hyperactivity disorder were matched with controls and attendances at the Accident
      and Emergency department and injury rates were compared. Children with attention
      deficit hyperactivity disorder are at a greater risk of injury and also attend
      the Accident and Emergency department more frequently. The pattern and causation
      of injury is also different. This paper identifies attention deficit
      hyperactivity disorder as a predisposing cause of injury.

PMID- 12789064
TI  - National multicentre study of acute intoxication in emergency departments of
      Spain.
AB  - OBJECTIVE: No studies have been published on global acute intoxication in Spanish
      emergency departments. We therefore designed a multicentre study to identify the
      epidemiology and management of intoxicated patients in Spain. METHODS: We
      prospectively recorded cases from 14 emergency departments during 14 randomized
      days between February and April 2000. We included all age groups and all kinds of
      acute intoxication patients (including alcohol), except food-related cases, inert
      foreign bodies and deaths before arrival at the emergency department. Phone calls
      to poison control centres and inpatients were not followed. RESULTS: A total of
      419 cases were recorded, 0.66% of emergency department visits. The incidence of
      intoxication was higher at weekends and on Mondays (P<0.001). The mean age was 33
      years (STD+/-18.10); males represented 56%, and 34.2% of patients arrived at the
      emergency department within the first 2 h. A total of 80% of patients were
      treated as outpatients, 3.7% were admitted to the intensive care unit, 6.7% were
      hospitalized, and 0.2% died. DISCUSSION: We recorded a slightly lower incidence
      than other European countries with the same epidemiological profile, except for a
      low incidence of acetaminophen cases. If we apply the European Association of
      Poisons Centres and Clinical Toxicologists gastric lavage criteria, there were an
      important number of unnecessary gut decontamination techniques in drug poisoning.
      Most patients were treated in emergency departments, without hospital admission.

PMID- 12789065
TI  - Carbon monoxide load in indoor carting.
AB  - Personal experience and reports of colleagues made the authors aware of a
      possible problem of carbon monoxide exposure in indoor carting arenas. Symptoms
      such as nausea, headache and altered coordination are not uncommon. This prompted
      us to register carbon monoxide levels in 15 healthy volunteers in a recreational
      carting event in a random arena. After two sessions of 10 min and a finale of 20
      min we measured a clear increase in carboxyhaemoglobin levels, up to a 16.5-fold
      increase. The mean rise in the carboxyhaemoglobin level (expressed as a
      percentage) was 2.06 (mean start carboxyhaemoglobin 0.49%, mean end
      carboxyhaemoglobin 2.55%). Nausea was noted in 53% of the drivers, headache and
      altered coordination in 33%, and 13% had a vague abdominal pain. The effects of
      carbon monoxide exposure during indoor carting should thus not be underestimated,
      and healthcare workers should be aware of the possible risks.

PMID- 12789066
TI  - Reliability of vital signs measured at triage.
AB  - OBJECTIVE: To determine the reliability of vital signs measured at triage in the
      emergency department. METHODS: The vital signs of all consenting ambulatory
      patients 16 years old and above presenting at triage were measured by the duty
      triage nurse as standard practice and then repeated by a single, blinded, trained
      observer within 2 min of the initial assessment using the same (manual or
      electronic) methods. The results were analysed using paired sample t-tests.
      RESULTS: No significant difference was found in the repeated electronic
      measurement of oxygen saturation [95% confidence interval (CI) -0.30-0.46,
      P=0.687] or repeated manual measurement of respiratory rate (95% CI -1.04-1.76,
      P=0.613). A statistically but not clinically significant difference of 2.43 bpm
      was found in the repeated electronic measurement of heart rate (95% CI 0.52-4.33,
      P=0.013). CONCLUSIONS: The manual and electronic measurements of vital signs at
      triage appear to be reliable.

PMID- 12789067
TI  - How to modify the risk-taking behaviour of emergency medical services drivers?
AB  - High speed and an aggressive style of driving are major risk factors for serious
      traffic accidents. Consequently, frontline emergency medical services vehicles
      have an increased collision risk. We report on two studies designed to modify the
      risk-taking behaviour of emergency medical services drivers. In the first study,
      we compared the travel intervals for a second tier unit using two different types
      of vehicles. We found that the replacement of a sports estate by an ambulance,
      which can be considered more or less as a change from a speedy and aggressive
      style of driving to a cautious style of driving with respect for the speed
      limits, resulted in an increase of the travel interval of only 10-20%. In the
      second study we found that the installation of a 'black box' in an emergency
      medical services vehicle, combined with well-defined guidelines for the drivers
      and a close monitoring system, provides fair but still not optimal results with
      regard to maximum speed and the occurrence of harsh braking events. Despite some
      limitations in the study designs, we conclude that for second tier units only a
      small amount of time is gained by high speed and an aggressive style of driving.
      Furthermore, we are convinced that a 'black box' is a good tool to modify the
      risk-taking behaviour of emergency medical services drivers.

PMID- 12789068
TI  - A more rational approach to medical disaster management applied retrospectively
      to the Enschede fireworks disaster, 13 May 2000.
AB  - As in any other medical discipline, developments in disaster medicine have
      occurred. A model for medical disaster management is briefly discussed and then
      applied retrospectively to the Enschede fireworks disaster (2000). Differences
      between the theoretical model and the actual situation are shown with respect to
      the number of casualties, the average severity of injury sustained, the medical
      rescue capacity, the medical transport capacity and hospital treatment capacity.
      It was concluded that the proposed model for the management of disasters with
      traumatically injured victims worked adequately.

PMID- 12789069
TI  - Integration of foreign and local medical staff in a disaster area: the Honduras
      and El Salvador experiences.
AB  - International medical aid after natural disasters may take various forms, ranging
      from self-sufficient military forces to single experts or specialists who
      function primarily as advisers. A model integrating foreign and local medical
      staff has not previously been reported. In response to the call for international
      aid by the Honduran and El Salvadorian governments in the wake of Hurricane Mitch
      in November 1998 and the San Salvador earthquake in January 2001, Israel sent
      medical supplies and 10 member teams of medical professionals to each country.
      The aim of the present paper is to describe the unique Israeli approach to
      providing healthcare in disaster areas by integrating foreign and local medical
      staff, and to discuss its advantages and disadvantages. The paper focuses on the
      experience of the two emergency medicine physicians on the team who were assigned
      to the Atlantida General Hospital in La Ceiba, Honduras. The same team in San
      Salvador subsequently applied the same approach.

PMID- 12789070
TI  - Cat bite in an old patient: is it a simple injury?
AB  - An 84-year-old woman bitten by her domestic cat developed a severe wound
      infection caused by Pasteurella multocida. Although she was treated with
      antibiotics according to the bacterial sensitivity, the infection progressed to
      sepsis and became complicated by transient renal failure caused by interstitial
      nephritis. The need in the emergency department for a thorough examination of
      patients with domestic animal-inflicted injuries, the indication for surgical
      debridement, and the isolation of the offender by early obtained cultures are
      considered. The administration of the properly chosen antibiotics and
      prophylactic vaccination against rabies and tetanus are discussed.

PMID- 12789071
TI  - Perimortem surgical intervention in cardiorespiratory arrest secondary to
      ruptured ovarian neoplasm.
AB  - Perimortem caesarean section is the intervention of choice for unresponsive
      cardiorespiratory arrest during the third trimester of pregnancy. We present a
      case of emergent surgical intervention in an arrested patient with an
      abdominopelvic mass, which revealed a ruptured granulosa cell ovarian neoplasm
      with haemoperitoneum.

PMID- 12789072
TI  - A pulmonary embolism case presenting with upper abdominal and flank pain.
AB  - BACKGROUND: The clinical manifestations of pulmonary thromboembolism are non
      specific, which makes this condition difficult to diagnose. A case of helical
      computerized tomography angiographically documented pulmonary thromboembolism,
      which initially presented as upper abdominal and flank pain, is described. CASE
      REPORT: A 46-year-old woman was referred to the emergency department for left
      flank and upper abdominal pain with diaphoresis and nausea. Her history included
      rheumatoid arthritis 3 years previously. During her examination the only abnormal
      finding was abdominal tenderness at the right upper quadrant and a positive
      Murphy sign without other systemic signs. A chest radiograph demonstrated an
      atelectatic line at the left lung base. The alveolar-arterial gradient was
      increased, and a ventilation-perfusion scan revealed a mismatch at the left upper
      and lower lobes, indicative of pulmonary thromboembolism. Helical computerized
      tomography angiography revealed filling defects on that side. The patient
      received anticoagulant therapy and gradually improved. CONCLUSION: The
      pathogenesis of the pain in the flank and upper abdomen is not known in this
      case. Unexplained upper abdomen and flank pain in a patient with risk factors for
      pulmonary thromboembolism, such as rheumatoid arthritis, should be investigated
      to rule out this treatable but potentially fatal condition.

PMID- 12789073
TI  - A case of Lemierre's syndrome.
AB  - Lemierre's syndrome is a rare but potentially life-threatening entity that
      follows an oropharyngeal infection. The syndrome is characterized by an
      antecedent acute oropharyngeal infection, with secondary suppurative
      thrombophlebitis of the internal jugular vein and septic emboli. In the pre
      antibiotic era, it had a 90% mortality rate. Now, with the advent of antibiotics,
      the prognosis is favorable, but delays in diagnosis may result in increased
      morbidity and mortality. Its incidence appears to be increasing. We present a
      case of Lemierre's syndrome, most notable for the patient's essentially benign
      physical examination and lack of clinical improvement with penicillin.

PMID- 12789074
TI  - Dorsal dislocation of the trapezoid.
AB  - Report of a dorsal dislocation of the trapezoid after a benign trauma, with only
      moderate symptoms and signs, without the necessity for further treatment.

PMID- 12789075
TI  - Re-expansion pulmonary oedema and circulatory shock in a 20-year-old man.
AB  - Re-expansion pulmonary oedema is a well-recognized rare complication of the
      treatment of spontaneous pneumothorax. It has been associated with death in 20%
      of cases. A fit 20-year-old man who had returned from holiday 2 days previously
      presented with a large left-sided pneumothorax of 10 days' duration. He had
      exhibited symptoms of chest pain and shortness of breath during the return
      flight. He showed no signs of respiratory distress at presentation to the
      Accident and Emergency Department, but after treatment with a chest tube in the
      ensuing 90 min developed severe unilateral re-expansion pulmonary oedema and
      circulatory collapse. Factors in the aetiology of the condition and prevention
      are considered.

PMID- 12789076
TI  - Drug-induced hyperthermia and muscle rigidity: a practical approach.
AB  - Body thermoregulation can be violently offset by drugs capable of altering the
      balance between heat production and dissipation. Such events may rapidly become
      fatal. The drugs that are involved in the eruption of such syndromes include
      inhalation anaesthetics, sympathomimetic agents, serotonin antagonists,
      antipsychotic agents and compounds that exhibit anticholinergic properties. The
      resultant hyperthermia is frequently accompanied by an intense skeletal muscle
      hypermetabolic reaction that leads to rapidly evolving rigidity, extensive
      rhabdomyolysis and hyperkalemia. The differential diagnosis should, however, rule
      out non-drug-induced causes, such as lethal catatonia, central nervous system
      infection or tetanus, strychnine poisoning, thyrotoxic storm and
      pheochromocytoma. Prompt life-saving procedures include aggressive body
      temperature reduction. Patients with a suspected drug (or non-drug)
      hypermetabolic reaction should be admitted into an intensive care area for close
      monitoring and system-oriented supportive treatment. We present six conditions,
      in decreasing order of gravity and potential lethality, in which hyperthermia
      plays an essential role, and suggest a clinical approach in such conditions.

PMID- 12789077
TI  - Pulmonary thromboembolism after long car travel (Tromboembolismo pulmonar tras
      viaje prolongado en automovil).
AB  - Prolonged immobility, especially bed rest for medical or surgical processes,
      constitutes one of the main risk factors for developing pulmonary
      thromboembolism. Immobility during extended plane or coach journeys (economy
      class syndrome) is not a frequent cause of serious pulmonary thromboembolism in
      healthy travellers. We report a case of serious pulmonary thromboembolism after a
      prolonged journey by car.

PMID- 12789078
TI  - Hyperbaric oxygen for carbon monoxide intoxications: do we know the dose?

PMID- 12789081
TI  - Chloroquine in the Ugandan market fails quality test: a pharmacovigilance study.
AB  - BACKGROUND: Antimalaria treatment failure has been partly attributed to poor
      quality antimalarials in the drug market. A 1998 survey in Kampala showed that
      55% of tablets and 62% of injection forms of chloroquine failed the quality test.
      OBJECTIVE: This study was carried out as a follow-up to establish the quality of
      chloroquine tablet and injection dosage forms in the Ugandan drug market from
      June - November 2001. METHODS: Chloroquine tablets and injection dosage forms,
      randomly purchased from pharmacies and drug shops in the four regions of Uganda,
      were assayed for content of the active ingredient according to the USP standard,
      using the HPLC method. RESULTS: Of the tablets samples surveyed, 39% failed the
      content test with 11% having sub-normal and 28% having supra-normal amounts,
      whilst 51% of the injection samples failed with 40% and 11% having sub-normal and
      supra-normal amounts respectively. CONCLUSION: There was overall improvement in
      the quality of chloroquine in Uganda compared with the 1998 figures, but the
      failure rates are still unacceptably high. The variations in the chloroquine
      amounts in both the tablet and injection forms may contribute to chloroquine
      toxicity or poor response during treatment. More vigorous pharmacovigilance on
      drugs entering the Ugandan drug market is needed.

PMID- 12789082
TI  - Family communication about HIV/AIDS and sexual behaviour among senior secondary
      school students in Accra, Ghana.
AB  - BACKGROUND: Sexually active adolescents in Ghana are increasingly at risk of HIV
      and other sexually transmitted infections. As a primary agent of socialization,
      the family can exert a strong influence on adolescent sexual behaviour.
      Therefore, to aid in the design and implementation of effective prevention
      programmes, it is important to understand the role of the family in influencing
      sexual behaviour among school-going adolescents. OBJECTIVES: To evaluate the
      relationship between family communications about HIV/AIDS and sexual activity and
      condom use among school-going adolescents in Accra, Ghana. METHOD: A sample of
      894 students (56.9% girls, 43.1% boys; mean age = 17.4 years, SD = 1.40) at two
      senior secondary schools in Accra completed a modified version of the Youth Risk
      Behavior Survey (YRBS) questionnaire, a self-administered instrument developed by
      the Centers for Disease Control and Prevention. Analytical techniques utilized
      included logistic regression and chi-square. RESULTS: Twenty-five percent of the
      participants reported being sexually experienced, and 73.6% had talked about
      HIV/AIDS with parents or other family members. Of the sexually experienced
      students, 64.7% initiated first sexual intercourse by age 16; and 55.7% did not
      use a condom at last sexual intercourse. Bivariate analysis showed significant
      gender differences in sexual activity, condom use, and family communication about
      HIV/AIDS. Logistic regression analysis showed that student-family communication
      about HIV/AIDS was not associated with sexual activity. However, communication
      about HIV/AIDS between students and parents or other family members increased the
      odds of using a condom at last sexual intercourse. CONCLUSIONS: The findings of
      this study suggest that prevention programmes that seek to educate Ghanaian
      school-going adolescents about sexual risk behaviour must strongly encourage
      communication about HIV/AIDS between students and family members.

PMID- 12789083
TI  - Severe anaemia in childhood cerebral malaria is associated with profound coma.
AB  - BACKGROUND: Severe anaemia in children with cerebral malaria has been associated
      with respiratory distress secondary to lactic acidosis and/or hypoxia. The
      ensuing metabolic derangement may further depress the level of consciousness
      culminating in presentation with profound coma. This association has poorly been
      studied. OBJECTIVE: To determine the relationship between profound coma at
      presentation and the presence of severe anaemia in children with cerebral
      malaria. METHODS: This cross-sectional study involved 100 children with cerebral
      malaria who were consecutively recruited at admission in the Paediatric emergency
      unit of Mulago hospital in Uganda from July to December 2000. Clinical and
      laboratory evaluation was done using the hospital's guidelines for the management
      of severe malaria. The exposure factor of interest was severe anaemia (Hb < 5.0
      g/dl) and occurrence of profound coma (Blantyre coma Scale 0) was the outcome
      measure. RESULTS: Severe anaemia and profound coma were seen in 20% and 9% of the
      children respectively. Severe anaemia was independently associated with profound
      coma, adjusted OR 1.34 (CI 1.17 - 1.95), p = 0. 002 and age < 3 years, adjusted
      OR 1.42 (CI 1.13 - 1.54), p = 0.001). Thirty percent of those with severe anaemia
      had deep sighing (acidotic) breathing compared to only 15% of those with
      haemoglobin (Hb) > 5 g/dl, OR 1.21 (CI 0.90 - 1.64), p = 0.118. There was no
      association between the malaria parasite density and severe anaemia. A similar
      proportion of those with severe anaemia regained consciousness within 24 hours
      compared to those with Hb > 5 g/dl (30 vs 42.5%), OR 1.56 (0.65 - 3.71), p =
      0.307. CONCLUSIONS: The findings suggest that profound coma in cerebral malaria
      may not only result from primary malaria encephalitis but possibly also from a
      metabolic dysfunction due to severe anaemia.

PMID- 12789084
TI  - Baseline survey of oral health of primary and secondary school pupils in Uganda.
AB  - BACKGROUND: Among the issues that determine the performance of a child at school
      is health. In recognition of this, the Uganda government has embarked on a school
      health program for the success of universal primary education. Although dental
      health is an important component of school health there is little information on
      it. OBJECTIVE: This study aimed at collecting information on dental health of
      pupils in school for evaluation and planning. DESIGN: A cross-sectional study
      using a multistage cluster sampling technique was used to select 685 children
      attending schools in 5 districts. Children were clinically examined for common
      illnesses/conditions. The oral examinations were done using simplified versions
      of Decayed, Missing, and Filled teeth (DMFT) index and Community Periodontal
      Index (CPI). Oral examinations also assessed presence of fluorosis. RESULTS: The
      pupils attending school were aged from 5 to 22 years. Sixty six percent (456)
      were found to be caries free with a group DMFT of 0.7. The D-component (decay)
      accounted for approximately 70% of the cases. Fifty nine percent of the pupils
      were found to have a healthy periodontium. Sixteen percent of the pupils were
      found to have some degree of fluorosis of whom the majority were from the
      highland districts of Kabale and Mbale. Urban school pupils were more likely to
      have caries (OR 1,69; 95% CI 1.21-2.37) than the rural. CONCLUSION: There is an
      upward trend in the caries prevalence when compared to studies done earlier. This
      study revealed a need to develop preventive programs alongside improvement of
      dental health services.

PMID- 12789085
TI  - The accuracy of self monitoring blood glucose meter systems in Kampala Uganda.
AB  - BACKGROUND: Many blood glucose self monitoring systems are privately and publicly
      used by people in Uganda and technical and human errors may occur during their
      operation. Many patients were referred to Kololo polyclinic laboratory to have
      their blood glucose checked because the values obtained on the patients' glucose
      meter systems did not tally with familiar clinical signs and symptoms. This
      prompted an experimental set up to check glucose meter systems using a larger
      number of patients. OBJECTIVE: The objective was to collate the technical
      conditions and standing operational procedures of four common glucose meter
      systems; observe the time, ambient temperature and humidity at which the meter
      systems operate locally; and compare the performance of three meter systems A, B,
      and C with the Sensorex glucose meter system on a number of capillary blood
      samples. SETTING: Kololo polyclinic laboratory--a privately run facility in
      Kampala, Uganda. DESIGN: An experimental set up to compare four glucose meter
      systems. METHODS: Instruction manuals of the four glucose monitoring systems were
      studied and used to familiarize with the meter operations. One hundred and
      fourteen capillary blood specimens were assayed for blood glucose. Blood glucose
      values were instantly read off the four randomly set meter systems A, B, C, and
      Sensorex, noting the time, ambient temperature and humidity. Results from meter
      systems A, B, and C were regressed against those of Sensorex using Epi-Info
      computer program. RESULTS: Blood glucose concentration levels on meter system A
      tallied with those on Sensorex meter system. However, those on meter system B and
      C were significantly lower and different. Temperature and humidity adversely
      affected the analytical performance of meter systems B and C in the Kampala
      environ. CONCLUSION: Some of the blood glucose monitoring systems in Kampala,
      Uganda are poor performers and may lead to the mismanagement of patients. There
      is need for a system to ensure national quality control of blood glucose
      monitoring systems.

PMID- 12789086
TI  - Screening for disability in a community: the 'ten questions' screen for children,
      in Bondo, Kenya.
AB  - BACKGROUND: Although the need for early identification and interventions of
      disabilities is evident, the current state of routine screening practice in Kenya
      needs intensive training of screeners before more rigorous techniques are
      introduced. OBJECTIVE: To compare the precision and practical utility of the 'ten
      questions' and EARC screens among the 2- 9 year olds in a community setting.
      METHOD: In this analytical comparative cross-sectional survey of two disabilities
      screening methods. multiphase sampling and multistage data collection procedures
      were employed. Quantitative research utilizing structured interview checklist was
      used for data collection. It described the prevalence rates of different types of
      disabilities using both methods. It analyzed the precision and practical utility
      of the two methods in a community setting. RESULTS: 64 of the 399 children under
      study were disabled (50.5% male and 49.5% female). The 'ten questions' picks up
      only those problems that are of great concern to families. EARC services are a
      more definite case defining process of measuring the existence and degree of
      disability in children. It screens the children who are severely disabled leaving
      out the mildly disabled and medical conditions which, when left untreated, could
      lead to possible disablement. CONCLUSION: Parents need to be sensitized about
      symptoms requiring the ten questions that can be used to screen out the
      potentially disabled children and the Education Assessment and Resource Centres
      (EARC) be used to diagnose the type and degree of the disability and refer the
      ill children for treatment. The basic needs of disabled children could be met in
      the community and do not require highly specialized personnel. They need to be
      localized and accessible.

PMID- 12789087
TI  - The complete paediatrician: attributes of good practice.
AB  - The attributes which the author considers help to make up good paediatric
      practice are discussed. Some of the problems associated with their achievement
      are examined. All of these ingredients can never be possessed by any one of us
      though each of us should have them as our aim. Their full spectrum, to be evident
      in practice, needs us to be members of a team.

PMID- 12789088
TI  - Breast cancer guidelines for Uganda.

PMID- 12789090
TI  - Tuberculosis in children at Mbarara University Teaching Hospital, Uganda:
      diagnosis and outcome of treatment.
AB  - BACKGROUND: The diagnosis of tuberculosis in children is difficult particularly
      in HIV infected children. The poor outcome following antituberculosis treatment
      usually reported in HIV infected children might be due, in part, to other HIV
      related chronic diseases wrongly diagnosed as TB. OBJECTIVE: The study examines
      the impact of HIV infection on the clinical features and diagnosis of children
      presenting with suspected tuberculosis in Mbarara University Teaching Hospital.
      It also examines the effect of various factors on the outcome of anti-TB
      treatment. METHODS: Children presenting with suspected TB were prospectively
      enrolled. Clinical data were recorded and investigations included Mantoux test,
      chest X-ray, HIV test and Z-N staining of various specimens for AAFBs where
      available. Patients were treated with standard, short-course anti-TB therapy, and
      followed-up for six months. They were then classified as "good outcome" if they
      improved and "poor outcome" if they deteriorated or died whilst on treatment.
      RESULTS: A total of 128 children were enrolled over an 18-month period. Four
      patients (3.1%) had a diagnosis of confirmed TB, 82 (64.1%) with "probable TB"
      and 42 (32.8%) with "suspected TB". Of 88 patients tested 43 (48.9%) were HIV
      positive. HIV positive patients had a higher frequency of failure to thrive,
      digital clubbing, enlarged lymph nodes and hepatomegaly; and a lower frequency of
      positive Mantoux tests. HIV positive patients were less likely to be classified
      as "confirmed or probable TB" (chi2 = 5.02, p = 0.025). Fifty six patients had a
      good outcome, 12 had a poor outcome and 60 defaulted before completing six months
      of treatment. HIV positive children were more likely to have a poor outcome
      (relative risk = 9.58, 95% CI 1.32 - 69.46). A diagnosis of "confirmed or
      probable TB" was associated with a good outcome (relative risk for poor outcome =
      0.14, 95% CI 0.05 - 0.36). CONCLUSION: HIV positive children with suspected TB
      frequently have signs that suggest the presence of other diseases such as
      Lymphocystic Interstitial Pneumonitis (LIP) and chronic bronchiectasis; and are
      less likely to have a diagnosis of "probable or confirmed TB" after
      investigations. Patients with an uncertain diagnosis of TB are less likely to
      improve on anti-TB therapy.

PMID- 12789091
TI  - The effect of an overpass on pedestrian injuries on a major highway in Kampala -
      Uganda.
AB  - OBJECTIVES: To describe the pedestrian population, their use of an overpass, and
      to assess pedestrian perceptions and responses to the risk of traffic crashes,
      determine pedestrian injuries in relation to traffic flow, and compare traffic
      crash and pedestrian injury rates before and after the overpass construction.
      SETTING: The study was conducted in Nakawa trading center approximately six
      kilometers from the center of Kampala city on a major highway. The trading center
      has a busy market, small retail shops, industries, a sports stadium, offices, low
      cost housing estates, schools, and an estimated population of 6,226 residents,
      15.1% of them students. METHODOLOGY: Pedestrian road behavior and traffic
      patterns were observed, and police traffic crash records reviewed, one year
      before and one year after overpass construction. A convenient sample of overpass
      and non-overpass users was interviewed to assess their perceptions of risk.
      RESULTS: A total of 13,064 pedestrians were observed (male: female ratio= 2.2:1).
      The overall prevalence of pedestrian overpass use was 35.4%. A bigger proportion
      of females (49.1%) crossed on the overpass compared to males (29.2%). More
      children (79.7%) than adults (27.3%) used the overpass. The majority of
      pedestrians (77.9%) were worried about their safety in traffic but only 6.6%
      thought of the overpass as an appropriate means to avoid traffic accidents.
      Traffic was not segregated by vehicle type. Mean traffic flow varied from 41.5
      vehicles per minute between 0730-0830 hours, to 39.3 vehicles per minute between
      1030-1130 hours and 37.7 vehicles per minute between 1730-1830 hours. The
      proportion of heavy vehicles (lorries, trailers, tankers, and tractors) increased
      from 3.3% of total vehicle volume in the morning to 5.4% in the evening (t =
      2.847, p <0.05); 44.0% of the collisions occurred in the evening with 35
      pedestrian casualties before and 70 after the overpass intervention. CONCLUSIONS:
      The prevalence of pedestrian overpass use was low with adult males least likely
      to use it. Pedestrians had a high perception of risk, which did not seem to
      influence overpass use. Pedestrian were more likely to be injured during slow
      traffic flows. There were more traffic crashes, and pedestrian injuries, but
      fewer fatalities after the construction of the overpass.

PMID- 12789092
TI  - Health seeking behavior by families of children suspected to have malaria in
      Kabale: Uganda.
AB  - BACKGROUND: Malaria is common among communities of Kabale district, and many
      young children die of the illness. Despite a good distribution of health
      facilities, able to handle malaria patients, families and individuals tend to
      depend on self-treatment, or private clinics where drugs used may be of doubtful
      quality. This study reports on health seeking behaviour by families with children
      suspected to have malaria. METHODOLOGY: A community-based, cross-sectional survey
      among 209 rural peasant families living in 12 villages, chosen from the 5 most
      malaria-affected sub-counties was done. Using a questionnaire, respondents'
      reactions to the disease and what decisions they took were recorded. Reasons for
      choices such as drugs used, location of treatment and malaria control methods
      were recorded. RESULTS: Ninety seven percent lived within easy reach of a public
      health facility. Over 2/3 knew how malaria was transmitted and how it presented.
      They believed it was best treated at public heath facilities using western type
      of medicine. Fifty percent of the children, who attended public health units,
      were treated within 24 of illness. Thirty eight percent of the caretakers knew
      how to correctly use chloroquine. The caretakers relied on fever, vomiting and
      refusal to feed as the main symptoms for their diagnosis of malaria. Only 31% of
      the families sought treatment from government health facilities. Fifty three
      percent of the families sought treatment from drug shops/vendors. Unfortunately
      only 38% of the families knew the correct regimen of chloroquine, 4.3% for sulpha
      doxine pyrimethamine and 0.5% for quinine. One quarter could afford malaria
      treatment, and one out of five missed treatment because of poverty. Concerning
      prevention, 90% stated at least one method but only 21.2% used them. CONCLUSIONS:
      Despite reasonable knowledge for diagnosis of malaria, awareness of correct
      treatment is limited. Paradoxically government health units appear to play a
      minor role in the treatment of malaria.

PMID- 12789093
TI  - High prevalence and morbidity of Schistosoma mansoni along the Albert Nile in
      Uganda.
AB  - An epidemiological cross sectional study of Schistosoma mansoni was conducted in
      two hyper endemic fishing villages of Rhino Camp and Obongi both in West Nile
      district in northern Uganda in 1991 and 1992. People with various water contacts
      were registered. A small group of civil servants and clergies with less water
      contact in the river Nile were studied for control of infection and morbidity. An
      overall prevalence of 81.5% of the 1367 people studied in both fishing villages
      of Rhino Camp and Obongi were excreting from 100 to > or = 500 Schistosoma
      mansoni eggs per gram (epg). 253 18.5% did not have Schistosoma mansoni eggs in
      their faeces. The influence of socioeconomic factors on infections in the study
      population was high among poorer illiterates who have frequent water contacts
      activities with River Nile. The sonomorphological abnormalities of periportal
      thickening (PT) due to Schistosoma mansoni were performed using ultrasound. 664
      patients were found to have various stages of (PT stages 0, I, II and III). A
      total of 703 (51.4%) patients did not have any periportal thickening (PT 0) in
      their livers despite the fact that 450 (32.9%) of them had Schistosoma. mansoni
      eggs in their faeces. The gravities of schistosomiasis in the two villages were
      similar showing greater morbidity in the younger adults.

PMID- 12789094
TI  - "Safe sex advice is good - but so difficult to follow". Views and experiences of
      the youth in a health centre in Kampala. From Kiswa Youth Clinic, Kampala,
      Uganda.
AB  - BACKGROUND: Young people in Uganda are advised by the Ministry of Health and
      other authorities to abstain from sex in order to avoid the human
      immunodeficiency virus (HIV), other sexually transmitted diseases (STD) and early
      pregnancies. If they cannot abstain they should use condoms and they should stay
      faithful to their partner. OBJECTIVE: To find out how young people perceive this
      advice and if they find it possible and realistic to follow. METHOD: In May and
      June 2000 twenty informants were selected by purposeful sampling and were
      interviewed in English. Given items were discussed. The interviews were recorded
      on tape, transcribed, extracted and sorted into categories in a qualitative
      research method. RESULTS: Most of the interviewed youth claimed that the advice
      is good and helpful but there are many obstacles. The results showed that
      information given in schools about condom use and safer sex behaviour is not
      always adequate. However, despite lack of clear health education messages, the
      risk of being HIV positive is of major concern to many youth. In addition, the
      expected lack of support if the test is positive is a common reason for
      abstaining from HIV testing. CONCLUSIONS: More discussions in society are needed
      to create consensus on safe sex messages presented to young people. HIV infection
      is a major concern but many young people abstain from testing, as they expect to
      receive inadequate support.

PMID- 12789095
TI  - The optimum pH for the derivative spectrophotometric determination of co
      trimoxazole in binary mixtures.
AB  - BACKGROUND: Although the experimental assessment of co-trimoxazole by use of
      derivative spectrophotmetry underscores the usefulness of this method due to its
      relative simplicity with which it can be carried out over the official United
      States Pharmacopoeia (USP) high pressure liquid chromatography (hplc) methods for
      this drug, suitable optimum conditions ought to be refined for its universal
      acceptability. OBJECTIVE: The objective of the present work was to obtain the
      optimum pH level for the UV assessment of co-trimoxazole. METHODS: The aqueous
      solutions of the individual drugs and their binary mixtures were buffered with
      Sodium Acetate-Acetic Acid buffer in the pH ranges 2-7 and scanned on zero order
      and on first-order derivative at the wave length between 200- 300 nm. RESULTS: At
      the same drug solution concentrations, spectral shifts occurred with change in
      pH, especially between the wavelengths 200 and 240 nm, only seeming to converge
      from approximate wavelength 260 nm onwards. Absorbance fluctuations were also
      observed at the same drug concentrations in the pH range 2 to 3.5 and 5 to 7 when
      the solutions were scanned, even at the wavelength where the spectra seem to
      converge. However there were no absorbance differences between pH 4 and 5.
      CONCLUSION: The UV spectrophotometric method is dependent on the optimum pH and
      this has been found to range from 4 to 5.

PMID- 12789096
TI  - Camurati-Engelmann's disease: a case report.
AB  - Camurati-Engelmann's disease is a rare condition worldwide. No cases have been
      documented in Uganda. A 26 year old female presented with a history of grinding
      pain in the limbs for over 20 years. Strong painkillers would temporally relieve
      the pain. She had an asthenic stature with generalised reduction in muscle bulk.
      Plain x-rays revealed the characteristic symmetrical thickening and sclerosis of
      the diaphyses of the appendicular skeleton and skull base, which is pathognomonic
      of Camurati-Engelmann's disease. Involvement of the metaphyses of these long
      bones as well as the metacarpal bones makes this an unusual case.

PMID- 12789097
TI  - Congenital lobar emphysema: a diagnostic challenge and cause of progressive
      respiratory distress in a 2 month-old infant.
AB  - Congenital lobar emphysema (CLE) is a rare congenital abnormality characterized
      by over inflation of a pulmonary lobe. It often presents a diagnostic and
      therapeutic dilemma. No case has been described in Uganda in the previous 10
      years. We describe a case of a 2 months old infant who presented with severe
      respiratory distress. A diagnosis of congenital left upper lobar emphysema was
      established on diagnostic imaging. Both his vascular anatomy and the bronchial
      wall were normal. He improved dramatically after surgery. The SaO2 normalized
      within 12 hours of Surgery (lobectomy) and the postoperative period was
      uneventful.

PMID- 12789098
TI  - A 14-year-old Nigerian female with idiopathic intracranial hypertension
      (Pseudotumor cerebri or benign intracranial hypertension).
AB  - A 14-year-old secondary school girl presented with acute onset severe generalized
      headache associated with vomiting and diplopia. These followed an initial fever,
      which responded to chloroquine. She had been on peflacine for a left knee septic
      arthritis until onset of her symptoms. The main findings on physical examination
      were mild obesity, left abducent nerve palsy, bilateral papilledema and evidence
      of resolving arthritis of her left knee. The results of her investigations,
      including a brain CT scan were within normal limits. A diagnosis of IIH was made.
      She responded satisfactorily to oral acetazolamide with complete resolution of
      her symptoms and signs within 12 days of hospitalization and 2 weeks of follow
      up.

PMID- 12789099
TI  - Corporate response to the HIV/AIDS epidemic in Uganda - time for a paradigm
      shift?
AB  - The HIV/AIDS epidemic is likely to remain the pre-eminent global health concern
      for the foreseeable future. In Uganda, while significant progress has been made
      by the government over the past decade in bringing down the rate of new
      infections, the HIV/AIDS burden in the country remains huge and vigilant efforts
      must be continued if this burden is to further decrease. Traditionally the
      government, supported by its international partners as well as local non
      government organizations and the community has borne the brunt of the costs of
      containing the epidemic in Uganda. While the corporate sector in the country has
      financially contributed towards the costs of some of the interventions that are
      currently in place to combat the HIV epidemic, there is largely a paucity of
      sustained and systematic corporate leadership in providing comprehensive HIV/AIDS
      programmes for their employees. A survey done by the authors of this paper
      reveals that most programmes undertaken in the private sector are of limited
      scope. We argue that there is more the corporate sector can do to more equitably
      share the HIV/AIDS burden, without necessarily jeopardizing its primary role -
      namely to maximize returns to shareholders. This paper proposes a conceptual
      framework of how companies can approach the issue of HIV/AIDS within their
      workforce and suggests that providing more comprehensive interventions may in
      some instances result in substantial cost savings through the prevention or at
      least delay of HIV/AIDS related consequences such as: frequent absences from
      work, erosion of company skills and knowledge through key employee deaths, and
      the costs of hiring and training replacements etc. This ultimately could result
      in positive financial returns to those companies that choose to pursue work place
      led HIV/AIDS control and prevention programmes.

PMID- 12789101
TI  - Gestational trophoblastic disease following complete hydatidiform mole in Mulago
      Hospital, Kampala, Uganda.
AB  - OBJECTIVES: To determine epidemiological characteristics and clinical
      presentation of complete hydatidiform mole (CHM) and complications associated
      with prophylactic chemotherapy with oral methotrexate. SETTING: Mulago hospital,
      Kampala. DESIGN: Prospective study. METHODS: Ninety-four patients with clinically
      and histologically confirmed complete hydatidiform mole admitted between 1/9/1995
      and 30/1/1998 were followed for periods ranging from 12 months to 30 months.
      Seventy-eight (83.0%) received a total of 187 courses of oral methotrexate (0.4
      mg/kg daily in 3 divided doses) as prophylactic chemotherapy. The main outcome
      measures were pre- and post-evacuation serum hCG levels and complications
      associated with oral methotrexate use. RESULTS: The prevalence of CHM was 3.42
      per 1000 deliveries. The mean age of subjects was 29.6 + 8.5 years. Eighteen
      women (19.1%) were nulliparous and mean gravidity was 8.3. Many women presented
      with high-risk disease. Risk factors for persistent trophoblastic disease were
      prior molar pregnancy, age<19 or >35 years and features of high-risk molar
      pregnancy. Twenty-four of the seventy-eight patients (30.7%) developed
      complications, mainly mucositis and haematological toxicity (leucopenia, anaemia
      and thrombocytopenia), commonly after 3 or more courses. CONCLUSION: CHM was
      common and many patients presented with high-risk disease. Oral methotrexate for
      prophylactic chemotherapy was tolerable and safe for the first 2 courses, but
      serious complications occur as the duration of treatment increases. Prophylaxis
      did not prevent development of (or death from) metastatic trophoblastic disease.
      RECOMMENDATIONS: Patients with CHM should be monitored for the development of
      post-evacuation trophoblastic disease. Those on prophylactic chemotherapy require
      close monitoring for the toxic effects of the drugs.

PMID- 12789103
TI  - Spectrophotometric determination of sulphamethoxazole and trimethoprim (co
      trimoxazole) in binary mixtures and in tablets.
AB  - BACKGROUND: The formulation of sulphamethoxazole (S) and trimethoprin (T) (CO
      TRIMOXAZOLE) in a combination mixture is very good pharmacologically since it
      enhances the efficacy of the individual drugs. However in this combination,
      difficulties in analysis on ordinary UV spectrophotometry are introduced because
      the two components give overlapping spectral bands on zero-order. The United
      States Pharmacopoea (USP)-recommended HPLC analytical method is quite expensive.
      OBJECTIVE: The objective of the present work was to assess whether derivative
      spectrophotometry could be used to circumvent the overlapping spectral bands of
      the components and hence use it for routine analysis of the drug. STUDY DESIGN:
      Experimental. METHODS: The aqueous solution of the individual drugs and their
      binary mixtures were scanned on zero order and on first derivative at the wave
      length between 200- 300 nm and at the pH of 4.5. RESULTS: The zero-order spectra
      of the compounds were completely overlapping. However the first-derivative scan
      offered better separation and hence T was determined from the absorbance at 237.6
      nm with negligible contribution from S (since at this point it was reading zero).
      Likewise S was determined at a wavelength of 259 nm when T was reading zero. The
      linear calibration graphs were obtained for 4-25 microg x ml(-1) of S and for 4
      20 microg x ml(-1) of T. CONCLUSION: The method is rapid, simple and can be
      applied successfully to assay a mixture of the two drugs in pharmaceutical
      preparations.

PMID- 12789102
TI  - Comparison of immunohistochemical and modified Giemsa stains for demonstration of
      Helicobacter pylori infection in an African population.
AB  - BACKGROUND: Modified Giemsa staining has been favoured by many researchers
      because it is easy to perform but, like many other stains, demonstration of the
      bacteria depends on its morphology. It has been arged in some research circles
      that some of the organisms in the gastric mucosa may not be true H.pylori.
      Immunohistochemical techniques have been developed and make use of anti H.pylori
      antibody, which reacts, with somatic antigens of the whole bacteria and have been
      found to correlate well with the presence of the bacteria. OBJECTIVE: To
      ascertain the efficacy of modified Giemsa stain in an African setting where
      H.Pylori seems quite prevalent. STUDY DESIGN: A laboratory-based study of two
      diagnostic tests in which modified Giema stain was compared with
      immunohistochemistry. METHODS: A total of 48 consecutive autopsy cases with no
      upper gastro intestinal diseases had their gastric mucosa stained for
      demonstration of H.pylori using both modified Giemsa and immunohisto chemical
      staining techniques. RESULTS: Twenty-seven cases of H.pylori were demonstrated by
      both techniques and 14 cases were not identified by the two staining methods. In
      2 cases immunostain could not demonstrate the bacteria but they were identified
      with modified Giemsa stain while in 5 cases the bacteria were identified by
      immunostain but not with modified Giemsa stain. The sensitivity of modified
      Giemsa stain was 85% (CI 66.5-98.8) while the specificity was 89% (CI 60.4 -
      97.8). The positive predictive value of modified Giemsa stain was 93% CI 75 -
      98.8%) while the negative predictive value was 74% (CI 48.6 - 89.9). The kappa
      statistic comparing the 2 stains was 0.69 (p value 0.00001) giving a good
      agreement between the two tests. CONCLUSION: With the above results the modified
      Giemsa stain, which is readily available in most African laboratories, is
      recommenced for diagnosis of H.pylori, a prevalent infection in Africa.

PMID- 12789104
TI  - Monitoring the severity of iodine deficiency disorders in Uganda.
AB  - BACKGROUND: Iodine deficiency disorders (IDD) cover a variety of pathological
      conditions including goitre, mental retardation and perinatal mortality in
      millions of individuals globally. IDD was initially identified as a problem in
      1970 and was confirmed in 1991. In 1993, the Uganda government introduced a
      policy of Universal Salt Iodization (USI) requiring all household salt to be
      iodized. After 5 years this study evaluates the USI programme. OBJECTIVES: To
      determine goitre prevalence rate, establish the proportion of household consuming
      iodized salt and determine the levels of iodine intake in the sample districts.
      METHODS: A sample of 2880 school children aged 6-12 years from 72 Primary schools
      in 6 districts of Uganda was studied in October 1999. Goitre was established by
      palpation, salt iodine was analysed by thiosulphate titration, while urinary
      iodine was analyzed using ICCIDD recommended method F in which iodine is detected
      colorimetrically at 410 nm. RESULTS: The over all total goitre rate was 60.2%
      down from 74.3 in 1991 and visible goitre was 30% down from 39.2% in 1991. The
      proportion of households taking adequately iodized salt was 63.8% and the median
      urinary iodine was 310 microg/L. Whereas 36% of 95 urine samples analysed in 1991
      had urinary iodine below 50 microg/L, only 5% of the 293 urine samples studied in
      1999 had the same urine levels. This represents a considerable improvement in
      iodine intake, which is confirmed by the fact that 63.8% of the study households
      consume adequately iodized salt. If maintained and evenly spread, this will
      enable Uganda to control IDD. CONCLUSION: USI has improved iodine intake in
      Uganda. However, iodine malnutrition is still a severe public health problem
      because some communities in this study such as in Kisoro still have low iodine
      consumption, while others such as Luwero now have iodine excess. The latter is
      likely to predispose to hyperthyroidism. RECOMMENDATION: The national set
      standard of household salt iodine of 100 ppm be revised. Locally produced salt be
      iodized, and a national iodine monitoring programme be instituted to ensure
      evenly spread consumption of adequately iodized salt by all communities in the
      country.

PMID- 12789105
TI  - A survey of the prevalence of refractive errors among children in lower primary
      schools in Kampala district.
AB  - BACKGROUND: Refractive errors are a known cause of visual impairment and may
      cause blindness worldwide. In children, refractive errors may prevent those
      afflicted from progressing with their studies. In Uganda, like in many developing
      countries, there is no established vision-screening programme for children on
      commencement of school, such that those with early onset of such errors will have
      many years of poor vision. Over all, there is limited information on refractive
      errors among children in Africa. OBJECTIVE: To determine the prevalence of
      refractive errors among school children attending lower primary in Kampala
      district; the frequency of the various types of refractive errors, and their
      relationship to sexuality and ethnicity. DESIGN: A cross-sectional descriptive
      study. SETTING: Kampala district, Uganda PATIENTS: A total of 623 children aged
      between 6 and 9 years had a visual acuity testing done at school using the same
      protocol; of these 301 (48.3%) were boys and 322 (51.7%) girls. RESULTS: Seventy
      three children had a significant refractive error of +/-0.50 or worse in one or
      both eyes, giving a prevalence of 11.6% and the commonest single refractive error
      was astigmatism, which accounted for 52% of all errors. This was followed by
      hypermetropia, and myopia was the least common. CONCLUSION: Significant
      refractive errors occur among primary school children aged 6 to 9 years at a
      prevalence of approximately 12%. Therefore, there is a need to have regular and
      simple vision testing in primary school children at least at the commencement of
      school so as to defect those who may suffer from these disabilities.

PMID- 12789106
TI  - Lay workers in directly observed treatment (DOT) programmes for tuberculosis in
      high burden settings: Should they be paid? A review of behavioural perspectives.
AB  - The current global tuberculosis (TB) epidemic has pressured health care managers,
      particularly in developing countries, to seek for alternative, innovative ways of
      delivering effective treatment to the large number of TB patients diagnosed
      annually. One strategy employed is direct observation of treatment (DOT) for all
      patients. In high-burden settings innovation with this strategy has resulted into
      the use of lay community members to supervise TB patients during the duration of
      anti-TB treatment. However, community involvement in health programmes is not a
      simple matter. There is often a need for continued motivation of community
      members in order to ensure sustainability of such projects. Lay workers may
      demand payment for work done particularly if this takes up a reasonable
      proportion of their time. TB treatment, by its very nature, lasts for a
      considerable period and this paper seeks to examine behavioural perspectives that
      attempt to address the issue of whether lay workers in such programmes should be
      paid for their services. The theories explored suggest intrinsic and extrinsic
      motivation as factors that lead people to volunteer for health programmes.
      Intrinsic motivation encompasses such feelings as empathy and altruism as well as
      other factors such as religious and cultural conviction. The authors argue
      however that in high-burden TB settings, these factors alone may be inadequate to
      provide continued motivation for lay worker involvement in health programmes.
      Extrinsic motivators, of which money is the strongest example, then also serve to
      keep sustained interest particularly in resource-limited settings where people
      expect payment for work done. The debate on whether lay workers in health
      programmes should be paid is thus compounded by issues such as what factors one
      believes are responsible for motivation in particular contextual settings; how
      long lay persons are expected to perform tasks at hand; the capacity that exists
      to pay them and the sustainability of the motivating option chosen. We recommend
      more qualitative research to be done on this issue in high TB burden settings.

PMID- 12789108
TI  - Screening extracts of Zanthoxylum chalybeum and Warburgia ugandensis for activity
      against measles virus (Swartz and Edmonston strains) in vitro.
AB  - A large proportion of the population in Uganda still relies on the use of plant
      extracts for treatment of various ailments. This study tested the claimed
      efficacy of some plants in the treatment of measles. In vitro antiviral assays
      were performed on extracts of two medicinal plants (Warburgia ugandensis and
      Zanthoxylum chalybeum) using measles virus (Edmonston and Swartz strains) as the
      test organisms. The assays performed were the neutralisation tests and the plaque
      reduction assays. Of the two plants Z. chalybeum had demonstrable in vitro
      antiviral activity in the seed extracts (titer reduction factor [TRF]: 100, for
      the ethanolic extract). The in vitro antiviral activity of the seed extracts was
      demonstrated to be due to compound 27-135D (TRF=1000), which was characterized by
      (1)H-NMR spectroscopy as the alkaloid skimmianine. Skimmianine had minimal
      toxicity to VERO cell lines. The petroleum ether extracts and the ethanolic
      extracts of Warburgia ugandensis had no inhibitory effect on cytopathic effect
      (CPE) formation, especially at the maximal non-toxic dose (MNTD). The extracts of
      W. ugandensis were highly toxic to VERO cell lines. The TRF values for the stem
      bark extracts of W. ugandensis were: water extract, 10; ethanolic extract, 1;
      fraction 27-163D, 100., which were regarded to be too low. Seed extracts of
      Z.chalybeum therefore probably cure measles due to the antiviral effect of
      skimmianine. It is not clear how extracts of W. ugandensis produce a beneficial
      response in measles disease, if at all.

PMID- 12789109
TI  - Sugar as a potential vehicle for vitamin A fortification: experience from Kamuli
      district in Uganda.
AB  - BACKGROUND: Despite measures put in place by the Uganda Government ten years ago
      to combat Vitamin A deficiency, the number of children suffering from this
      deficiency remains high. OBJECTIVE: To determine whether sugar may be used as a
      vehicle for vitamin A fortification. DESIGN: Cross-sectional descriptive study.
      SETTING: Kamuli district in Uganda. PATIENTS: One thousand one hundred and four
      children, and one thousand one hundred and two mothers or care-takers
      participated in the study. Sugar consumption patterns for the two age groups were
      determined. The methods of sugar storage in households were also determined. The
      children were aged 12 to 36 months, and mothers/caretakers 16 to 45 years.
      RESULTS: The overall proportion of households where sugar was consumed in the
      last seven days was 89.2% for children, and 88.3% for mothers/caretakers. Sugar
      was stored in covered tins in 67% of the households, and in covered baskets in
      28% of households. CONCLUSION: Sugar is a potential vehicle for fortification
      with vitamin A for Kamuli district. Storage of sugar in covered tins and baskets
      means that the stability of the vitamin A in the fortified sugar might not be
      affected by exposure to light.

PMID- 12789110
TI  - Community participation in primary health care (PHC) programmes: lessons from
      tuberculosis treatment delivery in South Africa.
AB  - BACKGROUND: Currently, there is renewed interest in the role community
      participation can play in Primary Health Care (PHC) programmes such as the
      delivery of effective anti-TB treatment to patients in high-burden settings.
      OBJECTIVES: To explore the feasibility of community participation in a high
      burden Tuberculosis Control Programme and to establish how supervision of
      treatment by lay volunteers compares with other methods of tuberculosis treatment
      delivery in the Northern Cape province of South Africa. METHODS: Prospective
      study involving 769 patients with confirmed pulmonary TB who were followed-up
      over a one-year period. Questionnaire interviews were also carried out with 135
      lay volunteers participating in the TB programme. RESULTS: One-third of the TB
      patients in the study received their treatment from lay volunteers in the
      community. Treatment outcomes for new patients supervised from the community were
      found to be equivalent to those who received treatment through other modes of
      treatment delivery (RR=1.04[0.94-1.16], p=0.435). For the re-treatment patients,
      community-based treatment was found to be superior (RR=5.89[2.30-15.09],
      p<0.001), to self-administered therapy. CONCLUSIONS: Health care planners should
      consider community participation as a viable way of ensuring accessibility and
      effectiveness in PHC programmes. There is need for more research into ways of
      achieving sustainability in resource-limited but high disease burden settings.

PMID- 12789111
TI  - Isolations of Bwamba virus from south central Uganda and north eastern Tanzania.
AB  - BACKGROUND: Bwamba virus (Genus Bunyavirus, family Bunyaviridae) is widely
      distributed in Africa. It causes many unidentified fevers because of its benign
      nature. OBJECTIVES: Samples of blood from patients were received at Uganda Virus
      Research Institute for diagnosis and confirmation of infections. Mosquito
      collections obtained in the O'nyong-nyong virus fever epidemic in Rakai in 1997
      were also investigated in an effort to confirm the vectors of O'nyong-nyong virus
      fever. METHODS: Patientsapos; serum and aliquots of mosquito pools were
      inoculated into the brain of 1-day old albino mice for attempted isolation of
      viruses. Positive isolates from sick mice were confirmed to be Bwamba virus by
      immunoflourescence assay microscopy and by plaque reduction neutralization tests.
      RESULTS: Three positive isolates of Bwamba virus were obtained. One of the
      strains was isolated from a sample of blood from a refugee in Burigi Camp, Ngara,
      in north eastern Tanzania; another strain was isolated from a health worker at
      the Uganda Virus Research Institute, working with the Rakai Project on HIV in
      Rakai district; while the third strain was isolated from a pool of 50 Anopheles
      funestus mosquitoes collected during the O'nyong-nyong virus fever epidemic in
      Rakai district in 1996/1997. CONCLUSIONS: Bwamba fever may be more common than it
      is usually thought to be. It is often mistaken for malaria and because it is a
      mild infection, many people do not go to hospital when infected. Further studies
      are needed to understand the epidemiology and natural history of Bwamba virus.

PMID- 12789112
TI  - Diverticular disease of the colon in Kampala, Uganda.
AB  - BACKGROUND: Diverticular disease of the colon has been reported to be a disease
      of the western world, however of recent it has been described in the Africans.
      OBJECTIVE: To study the clinical, demographic and radiological features of
      diverticular disease of the colon in Kampala, Uganda. METHODS: A retrospective
      and prospective descriptive study was carried out between January 1995-December
      1996 and January 1998-December 2000. The period January 1995-December 1996 was
      retrospective while January 1998-December 2000 was prospective. Thirty one
      consecutive patients were found to have diverticular disease of the colon at
      barium enema studies in two major hospitals and two private x-ray units in
      Kampala, Uganda. RESULTS: Thirty-one patients were seen during the study period;
      all were over 40 years of age. The commonest presenting complaint was rectal
      bleeding in 13 patients followed by abdominal pain in 12 patients. Most patients
      were found to eat a mixed type of diet, that is both low and high residue food.
      Radiologically the diverticulae appeared as flask shaped or rounded outpouchings
      at barium enema. This would sometimes be accompanied by a serrated appearance of
      the affected area. The commonest site affected was the sigmoid colon followed by
      the ascending colon. CONCLUSION: Although it was previously reported that
      diverticular disease was unknown in black Africans, it has been noted that cases
      are now being increasingly discovered. It is recommended that our index of
      suspicious for diverticular disease of the colon and its complications should
      also increase.

PMID- 12789113
TI  - Contraception and sexuality among the youth in Kisumu, Kenya.
AB  - BACKGROUND: A significant proportion of youth is infected by HIV and other
      sexually transmitted infections mainly through sexual intercourse, while the
      prevalence of unwanted pregnancies is rising. OBJECTIVE: To describe knowledge,
      attitude and practice and factors influencing sexual relationships and
      contraceptive practice among the youth in Kisumu town in western Kenya. METHODS:
      A descriptive cross-sectional study using a semi-structured questionnaire, key
      informant interviews, focus group discussions and informal conversations was
      carried out. The sample population of 388 youth aged 15-24 years was determined
      by simple random cluster sampling. Quantitative data were analysed using SPSS
      computer package. RESULTS: The majority of the youth are sexually experienced
      (73.5%) with most of the first sexual experiences occurring within the 15-19
      years age group. There is a high level of knowledge (99.2%) of contraceptive
      methods and a positive attitude towards contraception. However, the level of
      contraceptive use is relatively lower (57.5%) even for the sexually active.
      Factors influencing this practice are associated with the individual's background
      as well as health delivery systems and policy. CONCLUSION: There is a wide
      disparity between contraceptive knowledge and practice, which needs to be
      bridged. There is need to review policies and practices regarding reproductive
      health, sexuality and family life education.

PMID- 12789114
TI  - Injury Prevention Initiative for Africa: achievements and challenges.

PMID- 12789116
TI  - Clarifying the role of misoprostol in obstetrics.

PMID- 12789117
TI  - A comparative study of vaginal misoprostol and intravenous oxytocin for induction
      of labour in women with intra uterine fetal death in Mulago Hospital, Uganda.
AB  - BACKGROUND: Intrauterine fetal death is a major problem in obstetrics
      particularly in developing countries such as Uganda. Induction of labour in cases
      of fetal death using the available method of oxytocin is often difficult,
      expensive and frustrating. OBJECTIVES: To compare the effectiveness of vaginal
      misoprostol and intravenous oxytocin in induction of labour in women with
      intrauterine fetal death. METHODS: One hundred and twenty mothers were allocated
      in a randomised controlled way to one of the two induction groups. Oxytocin
      infusion was titrated based on patient response. The starting dose was 50 mcg
      (1/4 tablet) in misoprostol group and the dose was doubled every six hours till
      effective contractions were achieved. The two groups were compared for induction
      to delivery intervals, costs of the drugs and their safety during induction.
      RESULTS: The success rate within 48 hours of induction was 100% in the
      misoprostol group and 96.7% in oxytocin group. The mean induction to delivery
      time was significantly longer in the oxytocin group compared with the misoprostol
      group (23.3 versus 12.4 hours; p= 0.004). In the gestational age before 28 weeks,
      the induction to delivery interval in oxytocin group, was more than twice that
      used in misoprostol. However beyond 28 weeks, there was no significant
      difference. Women with intact membranes had induction to delivery interval of
      27.9 hours in the oxytocin group and 14.7 hours in the misoprostol group
      (p=0.002). When the membranes were ruptured, the values were 10.5 and 8.5 hours
      respectively (p=0.6). The induction to delivery time in cases with Bishop's score
      < 6 was 29.8 hours in the oxytocin group and 15.9 hours in misoprostol group
      (p=0.001). The corresponding values for Bishop's scores > 6 were 10 and 7.9 hours
      respectively (p=0.6). The majority of patients in misoprostol group (62%),
      required less than one tablet for successful induction. Misoprostol was cheaper
      (0.65 US dollars than oxytocin (7.86 US dollars) Retained placenta occurred in
      only 3.3% of the patients in the misoprostol group. There were no cases of
      ruptured uterus in both groups. CONCLUSION: Intravaginal misoprostol is more
      effective and cheaper than intravenous oxytocin for inducing labour in patients
      with intrauterine fetal death.

PMID- 12789119
TI  - Antibacterial and antifungal activities of extracts of Zanthoxylum chalybeum and
      Warburgia ugandensis, Ugandan medicinal plants.
AB  - Measles is a killer disease of children in Uganda. The treatment of the disease
      is mainly directed at the secondary microbial infections. A large proportion of
      the population in Uganda still relies on the use of herbal remedies, which have
      been claimed to produce beneficial responses. In this study, the efficacy of
      Warburgia ugandensis and Zanthoxylum chalybeum against common bacteria and fungi
      was investigated. Bactericidal and antifungal assays were done using extracts
      derived from Z. chalybeum and W. ugandensis (agar well diffusion, disc diffusion
      and colony count assays). All extracts (ethanolic, petroleum ether and aqueous)
      of Z. chalybeum did not show antimicrobial activity. Phytochemical investigations
      of Zanthoxylum chalybeum (seed) yielded a pure crystalline alkaloid (27-135 D)
      which was characterized as skimianine based on (1)H-NMR spectroscopy and
      comparison with spectra of authentic samples. Skimmianine did not have
      antimicrobial activity in this test system. W. ugandensis water extracts elicited
      antibacterial activity against both Escherischia coli and Staphylococcus aureus
      in the agar well assay but not in the disc diffusion assay. Warburgia ugandensis
      water extracts and fraction 27-163 D also showed antifungal activity against
      Candida albicans. Chromatography of extracts of Warburgia ugandensis stem bark
      afforded compound 49-169 K, which was characterized as the sesquiterpine
      muzigadial (by (1)H-NMR spectroscopy), which did not show antibacterial activity
      but had antifungal activity against C. albicans. Therefore, the claimed efficacy
      of W. ugandensis could be attributable to antibacterial and antifungal activity
      of its components. Since Z. chalybeum extracts had neither antifungal nor
      antibacterial activities, its mode of action is unclear from these results.

PMID- 12789118
TI  - Ebola haemorrhagic fever among hospitalised children and adolescents in northern
      Uganda: epidemiologic and clinical observations.
AB  - BACKGROUND: A unique feature of previous Ebola outbreaks has been the relative
      sparing of children. For the first time, an out break of an unusual illness-Ebola
      haemorrhagic fever occurred in Northern Uganda Gulu district. OBJECTIVES: To
      describe the epidemiologic and clinical aspects of hospitalised children and
      adolescents on the isolation wards. METHODS: A retrospective descriptive survey
      of hospital records for hospitalised children and adolescents under 18 years on
      the isolation wards in Gulu, Northern Uganda was conducted. All patient test
      notes were consecutively reviewed and non was excluded because being deficient.
      RESULTS: Analysis revealed that 90 out of the 218 national laboratory confirmed
      Ebola cases were children and adolescents with a case fatality of 40%. The mean
      age was 8.2 years +/- SD 5.6 with a range of 16.99 years. The youngest child on
      the isolation wards was 3 days old. The under fives contributed the highest
      admission (35%) among children and adolescents; and case fatality because of
      prolonged close contact with the seropositive relatives among the laboratory
      confirmed cases. All (100%) Ebola positive children and adolescents were febrile
      while only 16% had hemorrhagic manifestations. CONCLUSION: Similar to previous
      Ebola outbreaks, a relative sparing of children in this outbreak was observed.
      The under fives were at an increased risk of contact with the sick and dying.
      RECOMMENDATIONS: Strategies to shield children from exposure to dying and sick
      Ebola relatives are recommended in the event of future Ebola outbreaks. Health
      education to children and adolescents to avoid contact with sick and their body
      fluids should be emphasized.

PMID- 12789120
TI  - Contraceptive security, information flow, and local adaptations: family planning
      Morocco.
AB  - BACKGROUND: Many developing countries increasingly recognize and acknowledge
      family planning as a critical part of socio-economic development. However, with
      few health dollars to go around, countries tend to provide essential drugs for
      curative care, rather than for family planning products. Donors have historically
      provided free contraceptives for family planning services. Whether products are
      donated or purchased by the country, a successful family planning program depends
      on an uninterrupted supply of products, beginning with the manufacturer and
      ending with the customer. Any break in the supply chain may cause a family
      planning program to fail. A well-functioning logistics system can manage the
      supply chain and ensure that the customers have the products they need, when they
      need them. METHODOLOGY: Morocco was selected for the case study. The researchers
      had ready access to key informants and information about the Logistics Management
      Information System. Because the study had time and resource constraints, research
      included desktop reviews and interview, rather than data collection in the field.
      RESULTS: The case study showed that even in a challenging environment an LMIS can
      be successfully deployed and fully supported by the users. It is critical to
      customize the system to a country-specific situation to ensure buy-in for the
      implementation. CONCLUSIONS: Significant external support funding and technical
      expertise are critical components to ensure the initial success of the system.
      Nonetheless, evidence from the case study shows that, after a system has been
      implemented, the benefits may not ensure its institutionalization. Other support,
      including local funding and technical expertise, is required.

PMID- 12789121
TI  - Rapid detection of Mycobacterium avium subsp. paratuberculosis from cattle and
      zoo animals by nested PCR.
AB  - Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis, a
      suspect causative agent of Crohn's disease in man, is an emerging disease of
      international proportions affecting all ruminants. Early stage detection of
      Mycobacterium avium subsp. paratuberculosis infection would accelerate progress
      in control programmes. Despite new molecular approaches the standard diagnostic
      test for this disease is at present still the time consuming classic isolation
      procedure. Therefore, alternative diagnostic tests such as PCR, are needed for
      quick detection of infected animals. In this study, the conventional enrichment
      and isolation procedure and two IS900-based PCR methods for detection of
      Mycobacterium avium subsp. paratuberculosis in clinical samples from zoo animals
      and cattle were compared. A total number of 48 different clinical specimens
      obtained from animals suspected of having paratuberculosis were examined. The
      samples included faeces (n = 15) and organ tissues (n = 33). Of the faecal
      specimens two were identified as positive by nested PCR, whereas none was
      positive by single PCR or by culture. 28 organ specimens were found positive by
      culture. Mycobacterium avium subsp. paratuberculosis DNA was detected by nested
      PCR in 82% of the organ specimens identified positive by culture (23 samples) as
      opposed to 57% by single PCR (16 samples). Nested PCR also identified two
      positive samples that were not detected by either culture or single PCR. These
      findings show the great potential of nested PCR as a useful tool for the rapid
      diagnosis of paratuberculosis in animals.

PMID- 12789122
TI  - Bioavailability and stability of erythromycin delayed release tablets.
AB  - BACKGROUND: Erythromycin is available as the free base, ethylsuccinate, estolate,
      stearate, gluceptate, and lactobionate derivatives. When given orally
      erythromycin and its derivatives except the estolate are inactivated to some
      extent by the gastric acid and poor absorption may result. OBJECTIVES: To
      establish whether delayed release erythromycin tablets meet the bioequivalent
      requirement for the market. METHODS: Sectrophotometric analysis was used to
      determine the dissolution percentage of the tablets in vitro. High performance
      liquid chromatography and IBM/XT microcomputer was used to determine the
      bioavailability and pharmacokinetic parameters in vivo. RESULTS: Dissolution
      percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was
      completely released. The parameters of the delayed release tablets were Tlag 2.3
      hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F
      49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release
      tablet to erythromycin capsules was 105.31% CONCLUSION: The content, appearance,
      and dissolution bioavailability of delayed release erythromycin tablets conforms
      to the United States pharmacopoeia standards. The tablets should be stored in a
      cool and dry place in airtight containers and the shelf life is temporarily
      assigned two years.

PMID- 12789123
TI  - Menstruation in an unusual place: a case of thoracic endometriosis in Kampala,
      Uganda.
AB  - While pelvic endometriosis is relatively common, thoracic menstruation is rare. A
      report of what is believed to be the first case of thoracic endometriosis in
      Uganda is given. A 34-year-old female was complaining of on and off chest pain
      mainly on the right side. Clinically she had signs of pleural effusion and 500
      mls of altered blood were tapped from her right pleural space. Worried about a
      possibility of a malignant process, an urgent chest CT scan was performed. A
      right posterior pleural mass and pleural effusion were found. A pleural biopsy
      was taken and confirmed at histology as endometrial tissue. She did well on
      surgical excision and hormonal therapy. This was a rare case of endometriosis
      which shows the usefulness of imaging in the patient work up.

PMID- 12789125
TI  - Evaluation of the adjuvant effect of Escherichia coli heat-labile enterotoxin
      mutant (LTK63) on the systemic immune responses to intranasally co-administered
      measles virus nucleoprotein. Part I: antibody responses.
AB  - The adjuvanticity and immunogenicity of the heat-labile enterotoxin (LT) of
      Escherichia coli and of its non-toxic mutant, LTK63, was evaluated after
      intranasal administration of CBA mice with recombinant measles virus
      nucleoprotein (rMVNP) with or without LT or LTK63. Both LT and LTK63 were shown
      to be highly immunogenic with higher responses observed 4 weeks after the booster
      immunization. Although the nucleoprotein was immunogenic on its own, mice
      immunized with the nucleoprotein plus wild type LT produced significantly high
      antibody responses (p< 0.01). Mice that received the rMVNP with LTK63 also
      generated strong antibody responses to rMVNP. These antibodies were also
      significantly higher than those of rMVNP alone (p< 0.05). No significant
      differences were observed between groups of mice immunized intranasally with
      rMVNP plus LT or LTK63 (p> 0.05). Data on IgG antibody isotype profiles showed
      that IgG 1 and IgG 2a were predominant in mice immunized with rMVNP + LT or LTK63
      whereas IgG 1 predominated when rMVNP was given on its own implying that LT and
      LTK63 induce both Th1 and Th2-type immune responses. These results highlight the
      great potential of this non-toxic mutant of LT as a safe vaccine adjuvant.

PMID- 12789126
TI  - Childhood bacterial meningitis in Mbarara Hospital, Uganda: antimicrobial
      susceptibility and outcome of treatment.
AB  - BACKGROUND: The recommended antibiotic treatment of bacterial meningitis has come
      under scrutiny following frequent reports of in-vitro resistance by the common
      causative organisms to penicillin and chloramphenicol. OBJECTIVE: The study
      recorded the causative organisms, antibiotic sensitivity patterns and outcome of
      treatment of bacterial meningitis in children and examined the impact of various
      factors on the recorded outcome. DESIGN: This was a retrospective review of all
      case records of patients treated for bacterial meningitis over a one year period.
      SETTING: The study was set in the paediatric wards of Mbarara University Teaching
      Hospital, in south western Uganda. RESULTS: A total of 77 patients were treated.
      Among 56 patients with available CSF results the frequency of bacterial causes
      was as follows: H. influenzae 13(23.2%), coliforms 7(12.5%), uncultured Gram
      negative bacilli 7(12.5%), S. pneumoniae 5(8.9%) and N. meningitidis 3(5.4%).
      Most isolates tested were resistant to both penicillin and chloramphenicol, but
      all were sensitive to ciprofloxacin and perfloxacin. Twenty eight(36.8%) patients
      died, 22(28.9%) survived with sequelae and 15(19.7%) improved without sequelae.
      14/18 who received perfloxacin and/or ciprofloxacin survived compared with 23/47
      who did not: p=0.04). CONCLUSIONS: The high case-fatality rates and the high
      frequency of resistance to penicillin and chloramphenicol make a case for a
      review of the currently recommended antibiotic treatment of bacterial meningitis
      in this region. Fluoroquinolones need further evaluation as potential
      alternatives to chloramphenicol in the treatment of bacterial meningitis.

PMID- 12789127
TI  - Bioassay-guided studies on the cytotoxic and in vitro trypanocidal activities of
      a sesquiterpene (Muzigadial) derived from a Ugandan medicinal plant (Warburgia
      ugandensis).
AB  - Trypanosomosis is arguably the most important disease of man and his domesticated
      animals in the tropics. There are few compounds available for its treatment. This
      has exacerbated the development of drug resistance. There is therefore urgent
      need to search for newer compounds to treat this important disease. Medicinal
      plants represent a potential source of the drugs. This paper reports a bioassay
      guided study to search for possible biological activity (cytotoxic and
      trypanocidal) in two Ugandan medicinal plants. The methodology adopted was the so
      called 'ping-pong' approach, involving phytochemical purification (column
      chromatography and preparative thin layer chromatography), alongside biological
      studies (cytotoxicity, antibacterial, trypanocidal and antifungal studies).
      Phytochemical investigations of Zanthoxylum chalybeum (seed) yielded a pure
      crystalline compound, 27-135D, which was characterized by 'HNMR as the alkaloid
      skimmianine. Studies on stem bark yielded three alkaloids 27-165A, 27-173A and 27
      173B. All the above pure isolates, and the crude extracts of Z. chalybeum had
      neither biological activity nor cytotoxicity in the brine shrimp assay. A
      cytotoxic sesquiterpine, characterized as muzigadial, was isolated from W.
      ugandensis. It was highly toxic in the brine shrimp assay and also had in vitro
      trypanocidal activity against IL 3338 as well as IL1180; reference drug-resistant
      and drug-sensitive trypanosome strains respectively, comparable to diminazene
      aceturate and Geneticin (G418). Muzigadial also had antifungal activity against
      Candida albicans. It was concluded that the brine shrimp assay might be a useful
      predictor of trypanocidal activity of plant extracts and that muzigadial may be
      potentially valuable in the treatment of drug-resistant trypanosomosis.

PMID- 12789128
TI  - Knowledge, attitude and practice about sexually transmitted diseases among
      university students in Kampala.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) remain an important cause of
      morbidity and mortality among women in the child-bearing age. In order to
      institute appropriate preventive measures there is need to establish the profile
      of knowledge of the predisposing factors and causation of STDs, attitude to
      sexual practice and sexual patterns among the susceptible young people, such as
      university students. STUDY POPULATION: Non medical university students, Makerere
      University. DESIGN: Descriptive cross sectional study. METHODS: A detailed
      questionnaire identifying socio-demographic characteristics, sexual patterns,
      knowledge of STDs as well as attitudes towards prevention of STDs was
      administered to 400 non medical university students of Makerere University.
      RESULTS: Knowledge of the clinical features of gonorrhoea and AIDS was high; most
      knew the predisposing factors for STDs (multiple sexual partners 90%; unprotected
      sexual intercourse 93%; rape 81%; sex outside marriage 78%, and sex under the
      influence of alcohol 73%) but not so for syphilis. Males were three times more
      likely to contract STDs (27%) than their female (9%) counterparts. Whereas
      knowledge on methods of prevention was high (>90%) it was not followed by
      appropriate behavioural patterns. More female (33.5%) students had heard about
      Trichomonas vaginalis than males (23%); (((2) = 17.1; < 0.0001). This study has
      shown that more female than male students got information from their parents
      (((2) = 25.3; p < 0.001) while more male students had their source of information
      from previous sexual intercourse (((2) = 12.9; p = 0.001). CONCLUSION: The level
      of knowledge about STDs and their prevention is not matched by sexual behavioural
      patterns, and male students undertake more risky sexual behaviour. Sexual
      education should be introduced at the university as a means of increasing
      students' awareness about the problem and prevention of sexually transmitted
      diseases including HIV/AIDS.

PMID- 12789129
TI  - Splenic injury following trauma: the role of ultrasonography.
AB  - The spleen is the most commonly injured abdominal organ and this may follow
      accidental or non-accidental trauma. Three cases are presented of adult males who
      presented with pain in the left hypochondrium following trauma. Traumatic injury
      to the spleen was suspected and ultrasound confirmed this suspicion in the 3
      patients. The patients did well after splenectomy. Hence ultrasound evaluation of
      patents with history of trauma and left hypochondrial pain should be performed
      urgently in order to detect possible splenic rupture.

PMID- 12789130
TI  - Empty sella syndrome: incidental findings at computerised tomography.
AB  - A case is presented of a 43-year-old female patient who presented with severe
      dizziness, neck pain and headache. Clinical examination revealed diplopia with a
      horizontal gaze. Plain skull radiographs showed an enlarged sella turcica with no
      abnormal intracraial calcifications. Pre and post contrast axial and post
      contrast coronal computerised tomography scans through the sella turcica were
      done. An enlarged sella turcica filled with cerebrospinal fluid was demonstrated.

PMID- 12789131
TI  - Spinal African histoplasmosis simulating tuberculous spondylitis.
AB  - Spinal histoplasmosis is a rare disease condition that must be differentiated
      from other common inflammatory lesions of the spine such as tuberculosis. A case
      is presented of a pathologically proven African spinal hisptoplasmosis in a 39
      year-old female. Paraplegia and fever were the patient's clinical findings.
      Cervical plain radiography demonstrated a lytic destructive process of the lower
      cervical spine with radiographic signs similar to tuberculosis. The surgical
      management and chemotherapy of histoplasmosis are briefly discussed.

PMID- 12789132
TI  - The retained placenta.
AB  - The retained placenta is a significant cause of maternal mortality and morbidity
      throughout the developing world. It complicates 2% of all deliveries and has a
      case mortality rate of nearly 10% in rural areas. Ultrasound studies have
      provided fresh insights into the mechanism of the third stage of labour and the
      aetiology of the retained placenta. Following delivery of the baby, the retro
      placental myometrium is initially relaxed. It is only when it contracts that the
      placenta shears away from the placental bed and is detached. This leads to its
      spontaneous expulsion. Retained placenta occurs when the retro-placental
      myometrium fails to contract. There is evidence that this may also occur during
      labour leading to dysfunctional labour. It is likely that this is caused by the
      persistence of one of the placental inhibitory factors that are normally reduced
      prior to the onset of labour, possibly progesterone or nitric oxide. Presently,
      the only effective treatment is manual removal of placenta (MROP) under
      anaesthetic. This needs to be carried out within a few hours of delivery to avoid
      haemorrhage. For women in rural Africa, facilities for MROP are scarce, leading
      to high mortality rates. Injection of oxytocin into the umbilical vein has been
      suggested as an alternative. This method relies on the injected oxytocin passing
      through the placenta to contract the retro-placental myometrium and cause its
      detachment. Despite several placebo controlled trials of this technique, no firm
      conclusion have been reached regarding its efficacy. This may be due to
      inadequate delivery of the oxytocin to the placenta. Further trials are in
      progress to assess the optimal dose of oxytocin as well as the efficacy of a new
      technique designed to improve delivery of the oxytocin to the placental bed.

PMID- 12789134
TI  - Paediatric and neonatal resuscitation.

PMID- 12789133
TI  - Ten best readings on community participation and health.
AB  - This article reviews, in the opinion of the author, the 10 most influential
      reading on community participation and health development. The introduction notes
      that some of the articles do not address health directly but still do bring
      crucial interpretations to the topic. All articles view community participation
      as an intervention by which the lives of people, particularly the poor and
      marginalised can be improved. In addition, they all address the issue of the
      value of participation to equity and sustainability. The article considers the
      readings under four heading: concepts and theory; advocacy; critiques and case
      studies. It highlights the important contributions each reading makes to the
      understanding of participation in the wider context of health and health
      development. In conclusion, the article argues that participation has not met the
      objectives of planners and professionals, in good part, because it is
      questionable as to whether viewing participation as an intervention enables them
      to make correct assessments of its contribution to development. The bottom line
      is that participation is always about power and control, an issue planners and
      professionals do not want explicitly to address.

PMID- 12789135
TI  - Antioxidant vitamins and zinc for macular degeneration.

PMID- 12789136
TI  - Drug interactions.

PMID- 12789137
TI  - The role of TIGR and OPTN in Finnish glaucoma families: a clinical and molecular
      genetic study.
AB  - PURPOSE: The aim of the present study was to analyze the role of the two primary
      open angle glaucoma (POAG) genes, trabecular meshwork-induced glucocorticoid
      response (TIGR/MYOC) and optineurin (OPTN), in Finnish glaucoma families
      originating from southern coast of Finland. METHODS: In total, 136 patients were
      examined to determine their ophthalmological status. Genealogical studies were
      performed using church records. Direct PCR-sequencing of the coding regions of
      the TIGR and OPTN genes was performed in 11 subjects. RESULTS: Inheritance
      resembling autosomal dominant mode was detected in eight families with open-angle
      glaucoma. Glaucoma was diagnosed in 53 subjects, of them 44 had POAG, 7 had
      exfoliative glaucoma (EG), and 2 had other types of glaucoma. Of the first degree
      relatives, 22 out of 79 (28%) were glaucoma suspects. No mutations in these
      families were identified. Instead, two polymorphisms in the TIGR gene and three
      polymorphisms in the OPTN gene, in which one was novel, were found in three
      phenotypes: POAG, exfoliative glaucoma, and exfoliation syndrome. CONCLUSIONS:
      Our results give evidence that novel, unidentified genes will underlie POAG and
      exfoliation syndrome in the Finnish population.

PMID- 12789138
TI  - Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular
      neovascularization in a mouse model.
AB  - PURPOSE: RNA interference mediated by small interfering RNAs (siRNAs) is a
      powerful technology allowing the silencing of mamalian genes with great
      specificity and potency. The purpose of this study was to demonstrate the
      feasibility of RNA interference mediated by siRNA in retinal cells in vitro and
      in the murine retina in vivo. METHODS: siRNAs specific for enhanced green
      fluorescent protein (EGFP) and murine and human vascular endothelial growth
      factor (VEGF) were designed. In vitro studies in human cell lines entailed
      modulation of endogenous VEGF levels through chemically induced hypoxia. Effects
      of siRNA treatment on these levels were measured by ELISA. In vivo studies
      evaluating effects of siRNA on levels of EGFP and VEGF were performed by co
      injecting recombinant viruses carrying EGFP or hVEGF cDNAs along with the
      appropriate siRNAs subretinally in mice. Additional studies aimed at blocking
      production of endogenous mVEGF were performed using laser-induced choroidal
      neovascularization (CNV) in mice. Effects of in vivo treatments were evaluated
      ophthalmoscopically. Retinal/choroidal flat mounts were evaluated after perfusion
      with dextran-fluorescein. Alternatively, retinas were evaluated in histological
      sections or VEGF levels were measured in intact eyes using ELISA. RESULTS:
      Successful delivery of siRNA to the subretinal space was confirmed by observing
      significantly reduced levels of EGFP in eyes treated with Ad.CMV.EGFP plus EGFP
      directed siRNA. siRNAs directed against hVEGF effectively and specifically
      inhibit hypoxia-induced VEGF levels in human cell lines and after adenoviral
      induced hVEGF transgene expression in vivo. In addition, subretinal delivery of
      siRNA directed against murine Vegf significantly inhibited CNV after laser
      photocoagulation. CONCLUSIONS: Delivery of siRNA can be used in vitro and in vivo
      to target specific RNAs and to reduce the levels of the specific protein product
      in the targeted cells. This work suggests that RNA interference has potential for
      application to studies of retinal biology and for the treatment of a variety of
      retinal diseases, including those involving abnormal blood vessel growth.

PMID- 12789140
TI  - Write the right word.

PMID- 12789139
TI  - A novel PAX6 gene mutation in an Indian aniridia patient.
AB  - PURPOSE: A mutation in the PAX6 gene is thought to be the genetic cause of
      aniridia. Here we search for PAX6 gene mutations in Indian aniridia patients.
      METHODS: We amplified the coding exons of the PAX6 gene from the genomic DNA of
      15 unrelated aniridia patients using polymerase chain reaction technology. We
      then performed single-strand conformation polymorphism analysis and heteroduplex
      analysis to search for sequence variants. RESULTS: Sequencing of shifted bands in
      two patients revealed PAX6 gene mutations. One of these was a novel mutation,
      1180insA, located in exon 10 at the start of the PST domain. The other mutation,
      1080C->T (R240X), located in exon 9 within the homeodomain, and is another
      example of the most commonly reported PAX6 mutation. CONCLUSIONS: Although PAX6
      gene mutations and polymorphisms have been reported from various ethnic groups,
      we report for the first time the identification of PAX6 gene mutations in Indian
      aniridia patients.

PMID- 12789141
TI  - Management of the aging forehead: a review.
AB  - Aging in the upper third of the face manifests as rhytids and ptosis of the
      frontal, glabellar, and brow regions. Frown lines may occur even in younger
      individuals as a result of habitual or dynamic forehead muscular hyperactivity.
      Multiple treatment options have been advocated to address forehead rhytids and
      brow ptosis. This article reviews 3 of the more commonly used treatment options:
      collagen, botulinum toxin, and surgical forehead lifting. Additionally, an
      algorithm is proposed as a guideline for selecting the most appropriate option
      for a given condition.

PMID- 12789142
TI  - Changes in bite force and dentoskeletal morphology in prognathic patients after
      orthognathic surgery.
AB  - OBJECTIVE: We sought to evaluate the changes in bite force and dentoskeletal
      morphology in prognathic patients after orthognathic surgery. STUDY DESIGN:
      Twenty-four patients underwent orthognathic surgery to correct Class III skeletal
      and dental malocclusions. Ten patients who underwent Le Fort I and bilateral
      sagittal split ramus osteotomy of the mandible (ie, surgical correction of 2
      jaws) and 14 patients who underwent only bilateral sagittal split ramus osteotomy
      (ie, surgical correction of 1 jaw) were compared. Bite force was measured
      preoperatively and at 3, 6, and 12 months postoperatively. The dentoskeletal
      morphology was assessed through lateral cephalograms obtained preoperatively and
      12 months postoperatively. RESULTS: Twelve months postoperatively, the bite force
      was significantly greater in the patients who underwent surgery on 1 jaw than in
      the patients who underwent surgery on 2 jaws. Significant decreases in the gonial
      angle, occlusal plane angle, and anterior facial height were observed
      postoperatively in the patients with 1 surgically corrected jaw, but not in the
      patients with 2 surgically corrected jaws. Patients with 2 surgically corrected
      jaws experienced a greater increase in the Frankfort mandibular plane angle and a
      greater decrease in the posterior facial height than did those with 1 surgically
      corrected jaw. CONCLUSION: The difference in the preoperative-to-postoperative
      change in dentoskeletal morphology between the 2 groups is one of the factors
      responsible for the significant difference in postoperative bite force between
      the 2 groups.

PMID- 12789143
TI  - Microbiology of mandibular third molar pericoronitis: incidence of beta-lactamase
      producing bacteria.
AB  - OBJECTIVES: The purpose of this study was to evaluate the predominant flora
      associated with pericoronitis in third molars and to investigate the presence of
      beta-lactamase-producing strains. STUDY DESIGN: The third molars in 26 adults
      were evaluated by cultures with nonselective media and with selective media
      containing amoxicillin, pristinamycin, spiramycin, metronidazole, and spiramycin
      plus metronidazole. RESULTS: In the majority of cases (19/26), the flora found in
      an anaerobic atmosphere predominated. Obligate anaerobes were present in 21 of
      the 26 samples. The bacteria most commonly detected were alpha-hemolytic
      streptococci (26/26) and the genera Prevotella (15/26), Veillonella (15/26),
      Bacteroides (9/26), and Capnocytophaga (9/26). Amoxicillin and pristinamycin were
      the most active in reducing the anaerobic cultivable counts. beta-Lactamase
      producing strains were detected in 9 samples and were mostly bacteria of the
      genera Prevotella, Staphylococcus, and Bacteroides. CONCLUSIONS: These results
      highlight (1) the diversity of the microflora associated with pericoronitis and
      the importance of the anaerobic flora and (2) the existence of selection pressure
      related to the use of beta-lactams that may culminate in failure of prescribed
      penicillins.

PMID- 12789144
TI  - Blood-flow change and recovery of sensibility in the maxillary dental pulp after
      a single-segment Le Fort I osteotomy.
AB  - OBJECTIVE: To examine blood-flow change and recovery of sensibility in the dental
      pulp of maxillary incisors in patients undergoing a single-segment Le Fort I
      osteotomy. STUDY DESIGN: Fifty-four maxillary incisors in 14 patients were
      examined preoperatively and at 1 to 7 days, 14 days, 3 months, 6 months, and 12
      months postoperatively. The pulpal blood flow (PBF) was measured by laser Doppler
      flowmetry, and the pulpal sensibility (PS) was investigated by
      electrodiagnostics. RESULTS: The mean PBF dropped to its lowest value at 1 day
      postoperatively and subsequently increased except for a temporary drop on day 4.
      The PS was negative in all the examined teeth from 1 day to 14 days after
      surgery. Subsequently, the rate of the teeth with positive PS increased. At 3
      months postoperatively, the PS recovered in half of the examined teeth. The PBF
      value on day 1 was significantly higher in the teeth with positive PS at 3 months
      postoperatively than in those with negative PS at 3 months postoperatively.
      CONCLUSION: These results suggest that the decrease of the PBF in the maxillary
      incisors on 1 day after a single-segment Le Fort I osteotomy may affect the
      recovery of the PS in the short term after surgery.

PMID- 12789145
TI  - Magnetic resonance imaging of temporomandibular joint synovial fluid collection
      and disk morphology.
AB  - OBJECTIVE: The purpose of this study was to determine the features of synovial
      fluid, the shape of the disk, and the presence of disk displacement without
      reduction (DDsR) of the temporomandibular joint. STUDY DESIGN: A total of 612
      bilateral temporomandibular magnetic resonance images of 306 patients were
      reviewed. The status of the joint was categorized as follows: normal disk
      position, disk displacement with reduction, acute DDsR, subacute DDsR, and
      chronic DDsR. The disk shape was characterized as one of following: biconcave,
      cap-shaped, cup-shaped, flattened, eyeglass-shaped, amorphous, or discontinuous.
      The amount of synovial fluid was divided into 4 categories: not observed, small,
      moderate, or large. RESULTS: Synovial fluid collection was observed more
      frequently with subacute DDsR and when the disk was a folded shape. CONCLUSION:
      Synovial fluid collection, which was observed on T2-weighted magnetic resonance
      images, is more frequent in the early stage of DDsR. In addition, high signal
      intensity within the disk space should be considered a simple matter of fluid
      collection.

PMID- 12789146
TI  - Lateral pterygoid myotomy with reattachment to the condylar neck: an adjunct to
      restore function after total joint reconstruction.
AB  - OBJECTIVE: The purpose of this study was to investigate the results of performing
      a lateral pterygoid myotomy with reattachment to the condylar stump to restore
      more normal function after total joint reconstructive surgery. STUDY DESIGN:
      Twenty-four joints were reconstructed in 14 patients with stock Christensen
      chrome-cobalt prostheses. Patients were separated into 2 groups. Group I
      consisted of 4 joints without reattached lateral pterygoid muscle (-LPM), and
      group II consisted of 20 joints with reattachment of the lateral pterygoid muscle
      to the condylar stump (+LPM). Patients were evaluated at an average of 15 months
      postoperatively to assess mandibular movement. Group I was compared with group
      II, and statistical analysis was performed through the use of the Mann-Whitney
      test. Patient satisfaction was evaluated by using postoperative questionnaires.
      RESULTS: Group II had an average interincisal opening 7.3 mm greater than Group I
      (P <.001). Lateral movements averaged 3.86 mm in Group II versus 0.5 mm in Group
      I (P <.05). Protrusion was 2.83 mm greater in Group II than in Group I (P =
      0.53). CONCLUSION: The reattachment of the lateral pterygoid muscle to the
      condylar stump during total joint reconstructive surgery may provide the patient
      with greater interincisal opening, lateral excursions, and protrusive movement.
      The preliminary data from these small, nonrandomized groups are promising for
      improved function following total joint reconstruction.

PMID- 12789147
TI  - Amyloid deposition in the oral cavity: a retrospective study and review of the
      literature.
AB  - OBJECTIVE: A retrospective study was conducted to investigate the anatomic
      location and characteristics of amyloid deposition in the oral cavity. STUDY
      DESIGN: Seventeen biopsy specimens that were conclusive for a diagnosis of
      amyloidosis were assessed in terms of their anatomic location and histopathologic
      characteristics. RESULTS: Biopsy specimens were received from 13 patients-9
      females and 4 males. Six specimens were taken from the buccal mucosa, 4 from the
      tongue, 3 from the palate, 2 from the gingiva, and 2 from the floor of the mouth.
      Fifteen of 17 specimens (88%) had amyloid deposition in the subepithelial
      connective tissue in all locations. CONCLUSION: On the basis of our pilot data, a
      previously overlooked intraoral anatomic location, the buccal mucosa, may prove
      to be of higher diagnostic value than others previously reported in terms of
      obtaining a diagnosis of amyloidosis. In addition, the manner in which tissue
      biopsies are conducted for amyloid detection may be altered to create less
      morbidity.

PMID- 12789148
TI  - New oral findings in Cohen syndrome.
AB  - Cohen syndrome is a hereditary disorder transmitted as an autosomal-recessive
      trait. Approximately 100 cases have been reported in the genetic and pediatric
      literature. Despite the fact that oral alterations are often observed in these
      cases, only 1 work has been published addressing this specific topic, and it
      tended to concentrate on periodontal abnormalities. The present study details 2
      new patients, 2 brothers (8 and 11 years old), and mainly consists of an analysis
      of the dentomaxillary anomalies that until now have not been studied in depth. In
      this study, the mandible, characterized as hypoplastic in Cohen syndrome, appears
      to be in a normal position; what really exists is a maxillary hyperplasia of
      genetic origin. We also put forward an observation hitherto undescribed in the
      literature: dental agenesis.

PMID- 12789149
TI  - Treatment of severe erosive gingival lesions by topical application of clobetasol
      propionate in custom trays.
AB  - OBJECTIVE: We sought to describe the response of patients with severe erosive
      gingival lesions to treatment with clobetasol propionate in Orabase paste
      administered in trays. The adverse effects were also recorded. STUDY DESIGN: A
      descriptive pretest/posttest clinical study with no control group (33 patients
      total) was developed. All patients received repeated applications of 0.05%
      clobetasol propionate plus 100,000 IU/cc of nystatin in Orabase paste. Over the
      48-week period, the pain levels, ulcerations, presence of atrophy, and the
      patients' daily activities were recorded, and Likert scales were used to classify
      each outcome as either a complete recovery, excellent, good, poor, or failed. The
      presence of any adverse effect was also noted. RESULTS: At the end of the study
      period, the pain and ulceration had disappeared (complete response) in 100% of
      the sample (33/33; 95% confidence interval = 89.4%-100%), and there was a
      complete recovery of daily activities and remission of atrophy in 93.9% (31/33;
      95% confidence interval = 79.8%-99.3%) and 21.2% (7/33; 95% confidence interval =
      9.0%-38.9%) of the patients, respectively. No adverse effects related to the
      treatment were observed. CONCLUSIONS: The application of an Orabase paste of
      0.05% clobetasol 17-propionate plus 100,000 IU/cc of nystatin by means of a tray
      appears to be an efficacious treatment for severe erosive gingival lesions.

PMID- 12789150
TI  - A 4-year longitudinal evaluation of xerostomia and salivary gland hypofunction in
      the Women's Interagency HIV Study participants.
AB  - OBJECTIVES: Our purpose was to conduct a longitudinal investigation of xerostomia
      and salivary gland hypofunction in a national cohort of HIV-positive and at-risk
      HIV-negative participants in the Women's Interagency HIV Study. Study design.
      Data included responses to a dry mouth questionnaire, clinical evaluations of
      major salivary glands, and unstimulated and chewing-stimulated whole salivary
      flow rates. Repeated measures regression models were used to determine factors
      associated with xerostomia and salivary gland hypofunction. RESULTS: Significant
      univariate associations were found between HIV status and reports of "too little
      saliva" (P <.0001), < or = 0.1 mL/min, unstimulated saliva (P =.01), and lack of
      saliva upon palpation of parotid (P =.02) and submandibular/sublingual salivary
      glands (P =.03). Adjusted odds of reports of "too little saliva" were
      significantly higher for HIV-positive participants (odds ratio [OR] = 2.44; 95%
      CI, 1.49 - 3.97; P =.0004) than for HIV-negative participants. Among HIV-positive
      women, adjusted odds of reports of "too little saliva" and of < or = 0.7 mL/min
      chewing-stimulated saliva were significantly higher for those with CD4 < 200 (OR
      = 1.58; 95% CI, 1.07-2.34; P =.022; and OR = 1.53; 95% CI, 1.05-2.23; P =.027,
      respectively) and for those with CD4 200-500 (OR = 1.47; 95%CI, 1.07-2.02; P =
      0.016; and OR = 1.37; 95% CI, 1.01-2.31; P =.001, respectively) than for those
      with CD4 > 500. Also, adjusted odds of < or = 0.1mL/min unstimulated saliva and <
      or = 0.7 mL/min chewing-stimulated saliva were significantly higher in women on
      highly active antiretroviral therapy (HAART) (OR = 1.25; 95% CI, 1.05 - 1.50; P
      =.014) than in women not on HAART (OR = 1.34; 95% CI, 1.01 - 1.79; P =.044).
      CONCLUSIONS: HIV-positive women are at a significantly higher risk for xerostomia
      and salivary gland hypofunction than HIV-negative women, and low CD4 cell counts
      and HAART use are significant risk factors for these conditions.

PMID- 12789151
TI  - Low-grade malignant Triton tumor of the oral cavity: a case report.
AB  - Malignant Triton tumor (MTT) is a malignant peripheral nerve sheath tumor showing
      rhabdomyoblastic differentiation. It is considered a high-grade neoplasm with
      poor outcome. This report describes an MTT appearing in the oral cavity. On
      histologic examination the encapsulated lesion was composed of interlacing
      fascicles of spindle cells and scattered, large, strap-like pleomorphic cells
      with abundant eosinophilic cytoplasm. No cross striations were seen. Examination
      of levels through the tissue showed a total of only 4 normal mitoses and no
      necrosis. Immunohistochemistry demonstrated diffuse S100 positivity in the
      spindle cells. The large pleomorphic cells were weakly positive for alpha
      sarcomeric actin and myoglobin, although variably but strongly positive for
      desmin. Management involved a small en bloc resection of the maxilla. After 33
      months there was no sign of recurrence or distant metastasis. It was concluded
      that low-grade variants of MTT occur that do not have an aggressive clinical
      course.

PMID- 12789152
TI  - Oral and dental manifestations of vitamin D-dependent rickets type I: report of a
      pediatric case.
AB  - Vitamin D-dependent rickets type I (VDDRI) represents an autosomal recessive
      hereditary defect in vitamin D metabolism. Patients with VDDRI have mutations of
      chromosome 12 that affect the gene for the enzyme 1-alpha-hydroxylase, resulting
      in decreased levels of 1,25(OH)(2) vitamin D. Clinical features include growth
      failure, hypotonia, weakness, rachitic rosary, convulsions, tetany, open
      fontanels, and pathologic fractures. The oral and dental manifestations of VDDRI
      have not been described. Here we present the case of a 10-year-old girl affected
      by VDDRI, as established by the combination of clinical and radiographic
      findings, family history, and laboratory values. Dental examination revealed
      markedly hypoplastic, yellowish-to-brownish enamel in all permanent teeth,
      malocclusion, and chronic periodontal disease. Large quadrangular pulp chambers
      and short roots were evident in dental radiographs. Light microscopic and
      ultrastructural examination showed abnormalities of dental hard tissues,
      affecting both enamel and dentin. The differential diagnosis and treatment of
      VDDRI are discussed.

PMID- 12789153
TI  - Matrix metalloproteinase 2 and matrix metalloproteinase 9 expression in human
      oral squamous cell carcinoma and the effect of protein kinase C inhibitors:
      preliminary observations.
AB  - OBJECTIVE: The purpose of this study was to investigate gelatinase
      (matrixmetalloproteinase [MMP]-2 and MMP-9) expression in oral squamous cell
      carcinoma (OSCC) and to explore the mechanisms that may inhibit gelatinase
      activity. STUDY DESIGN: Thirty biopsy specimens of OSCCs were examined by means
      of immunohistochemistry. Supernatants from primary cultures of human oral mucosal
      keratinocyte and oral cancer-derived cells (KB and OC2) were analyzed by means of
      gelatin zymography. Furthermore, protein kinase C (PKC) inhibitors (H7 and
      staurosporine) were added to test how they modulate gelatinase production in
      human oral cancer cells. RESULTS: MMP-2 and MMP-9 expression was significantly
      higher in oral SCCs and was located in discrete clusters of tumor cells. Oral
      mucosal keratinocyte cultures, KB, and OC2 were found to secrete and produce MMP
      2 and MMP-9. However, the amounts of MMP-2 and MMP-9 were highly elevated in the
      2 oral cancer cell lines in comparison with oral mucosal keratinocyte cultures (P
      <.05). In addition, PKC inhibitors were found to decrease MMP-2 and MMP-9
      activities in oral cancer cells (P <.05). CONCLUSION: Taken together, human oral
      SCCs produce MMP-2 and MMP-9 in vivo and in vitro, and gelatinase activity is
      down-regulated by PKC inhibitors in vitro. PKC inhibitors suppressing MMP
      production and/or activity may represent valuable therapeutic agents through
      their influence on the pathogenesis of OSCC. These agents may prove clinically
      useful in combination with standard therapeutic modalities for the treatment of
      patients with oral cancer.

PMID- 12789154
TI  - Oral spindle cell neoplasms: a review of 307 cases.
AB  - The infrequent exposure of pathologists to soft tissue spindle cell neoplasms
      coupled with overlapping histologic patterns can often make diagnosis
      challenging. We reviewed all nonodontogenic spindle cell neoplasms seen between
      1982 and 2002 (86,162 total accessions). Diagnoses were reclassified according to
      current standards supplemented with immunohistochemistry. Of the 307 neoplasms
      reviewed (0.36% of total accessions), neural tumors were the most common benign
      entities, accounting for 21% of total cases. Kaposi's sarcoma was the most common
      malignancy, accounting for 67% of all cases. Diagnoses were revised for 57 cases.
      Schwannoma and neurofibroma were most commonly revised to palisaded encapsulated
      neuroma. There were 8 myofibromas and 1 inflammatory myofibroblastic tumor. There
      were no oral leiomyomas; that is, all 4 originally reported cases were
      reclassified as myofibroma, palisaded encapsulated neuroma, and solitary fibrous
      tumor. With the exception of Kaposi's sarcoma, oral soft tissue sarcomas were
      rare; most benign lesions were neural in origin. The relatively high prevalence
      of some tumors, such as myofibroma, likely reflects the use of
      immunohistochemistry in the diagnosis of spindle cell tumors.

PMID- 12789155
TI  - Hajdu-Cheney syndrome (acro-osteolysis): a case report of dental interest.
AB  - Hajdu-Cheney syndrome (acro-osteolysis) is a rare disorder of bone metabolism
      characterized by progressive lytic lesions in a number of bones. Constant
      features of this condition include an osteoporotic skeleton, acro-osteolysis, and
      a shortened lower third of face. The purpose of this report was to focus on the
      craniofacial and oral manifestations of the disorder in a 9-year-old boy.

PMID- 12789156
TI  - Effect of root resection on the apical sealing ability of mineral trioxide
      aggregate.
AB  - OBJECTIVE: The purpose of this in vitro study was to determine the minimum depth
      of mineral trioxide aggregate (MTA; ProRoot; DENTSPLY/Tulsa Dental, Tulsa, Okla)
      required to maintain an apical seal following root resection. Study design. In 10
      instrumented teeth, MTA was used to obturate the apical 6 mm of the root canal
      and was allowed to set for 48 hours. Leakage was determined by means of a fluid
      filtration method at a pressure of 20 cm H(2)O. Leakage was measured before root
      resection, and after 3, 4, 5, and 6 mm apical resections. Data were analyzed by
      means of a Kruskal-Wallis one-way analysis of variance with P <.05. RESULTS:
      Fluid leakage was shown to increase after each resection, but did not reach
      statistical significance (P <.05) until 4 mm of the apex had been removed.
      CONCLUSION: The results indicate that root resection did not significantly affect
      the sealing ability of MTA when at least 3 mm of the MTA remained. Although there
      was a statistically significant difference in leakage following the 4 mm
      resection, it is unknown what the biological difference would be between the 3 mm
      and 4 mm resections.

PMID- 12789157
TI  - Tooth exfoliation and necrosis of the crestal bone caused by the use of
      formocresol.
AB  - A 68-year-old woman received a formocresol pulpectomy of the right lower lateral
      incisor. The temporary restoration was lost within hours. The next day, the
      patient suffered continuous pain, the gingiva sloughed, and the alveolar bone was
      exposed. Four days after treatment, the patient complained of moderate pain. Six
      days after the pulpectomy, the tooth spontaneously exfoliated. At this time she
      was referred to our hospital. The clinical diagnosis was chronic alveolitis.
      Treatment consisted of irrigation of the area. Three weeks after the pulpectomy,
      the dull pain had subsided, but the alveolar bone of the area showed increased
      mobility. Five weeks after the pulpectomy, the mobility of the alveolar bone was
      more significant and a sequestrectomy was performed with the patient under local
      anesthesia. The sequestrum of necrotic bone was approximately 10 x 5 x 5 mm in
      size. The patient has been symptom-free for 2 years since the sequestrectomy.

PMID- 12789158
TI  - Effects of root-end filling materials on fibroblasts and macrophages in vitro.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of 4 root-end
      filling materials (mineral trioxide aggregate [MTA], intermediate restorative
      material [IRM], amalgam, and Retroplast) on cell growth, cell morphology, and
      cytokine (interleukin [IL]1beta and IL-6) production in mouse fibroblasts and
      macrophages. STUDY DESIGN: Millipore culture plate inserts with freshly mixed or
      set root-end filling material were placed into 6-well cell culture plates with
      already attached mouse fibroblasts or macrophages. Cells cultured with only the
      Millipore culture plate inserts served as a control. After a 3-day incubation,
      cell morphology was examined, and the total cell number per well was counted and
      analyzed by using 1-way analysis of variance. For cytokine assay, mouse
      macrophages were incubated in 24-well flat-bottom plates with set root-end
      filling material disks in the bottom. Cells cultured without the material disks
      served as negative controls, and cells cultured with lipopolysaccharides served
      as positive controls. After 24-hour incubation, culture media were collected for
      cytokine assay by using enzyme-linked immunosorbent assay. RESULTS: All root-end
      filling materials inhibited the cell growth of mouse fibroblasts and macrophages.
      There was no growth in the originally seeded cells in the fresh IRM, the fresh
      Retroplast, and the set IRM group. There was no difference between MTA and
      amalgam for cell growth either in the fresh material groups or in the set
      material groups. The total cell number in the set Retroplast group was
      significantly less than that in the set MTA group. Morphologically, MTA was
      characterized by denatured medium proteins and dead cells adjacent to the
      material, which were observed only in the fresh MTA group. There was no detected
      cytokine production in any of the tested material groups. CONCLUSION: All root
      end filling materials inhibited cell growth, and none induced IL-1beta and IL-6
      production.

PMID- 12789159
TI  - Comments on noise and resolution of the DenOptix radiography system.
AB  - OBJECTIVES: Relatively low signal/noise (S/N) ratios, which are not substantiated
      by the results reported here, have been reported for the DenOptix digital
      intraoral radiography system. Unexplained poor performance has also been reported
      for imaging of the gingival tissue. I sought to discover the probable sources of
      the discrepancies and to present data on the effects of pixel size and screen
      type on noise and resolution. Methods. S/N ratios were measured with an aluminum
      phantom, and noise was measured with a step-wedge. The radiographs were scanned
      with both default and special, manufacturer-supplied software to obtain 8-bit
      rescaled data and 16-bit raw data. The data were compared with previously
      published data for the DenOptix and Digora systems. RESULTS: The S/N ratios of up
      to 17 obtained here were much higher than previously reported. Previously
      reported low ratios and poor performance for the imaging of gingival tissue were
      likely caused by digital clipping of 8-bit images, which should not affect bony
      tissue images in normal clinical radiographs. With nonstandard white phosphor
      screens, S/N ratios of up to 18 were observed, with only a minor loss of
      resolution. For the smallest pixel size (42 micro m), resolutions of > or =10
      line-pairs/mm and > or =8 line-pairs/mm were observed for standard blue and white
      phosphor screen types. If the smallest pixel size is selected, the noise
      increases by only 25%, which is much less than the theoretical increase.
      CONCLUSIONS: In terms of both noise and resolution, the DenOptix system compares
      favorably with the Digora system. S/N ratios for the DenOptix system are
      comparable with the best of 6 previously tested systems. With the DenOptix
      system, the smallest pixel size produces both the best resolution and the best
      noise characteristics. The selection of 16-bit images prevents digital clipping
      of 8-bit images.

PMID- 12789160
TI  - Three new cases of salivary duct carcinoma in the palate: a radiologic
      investigation and review of the literature.
AB  - Salivary duct carcinoma (SDC) is a rare, extremely aggressive malignancy arising
      in the ductal epithelium of the salivary glands. Radiologic investigations of and
      reports on minor salivary gland SDC are very rare. We present 3 cases of SDC of
      the palate with the attendant radiologic features and clinicopathologic findings.
      We also review English-language reports with radiologic findings regarding SDC
      and minor salivary gland SDC. MR imaging findings such as low signal intensity on
      T2-weighted images, infiltrative margins, and poor enhancement, in particular,
      should be recognized as indicators of high-grade malignancy such as SDC and, as
      such, should be considered when making a differential diagnosis.

PMID- 12789161
TI  - Does joint effusion on T2 magnetic resonance images reflect synovitis? Part 3.
      Comparison of histologic findings of arthroscopically obtained synovium in
      internal derangements of the temporomandibular joint.
AB  - OBJECTIVES: To evaluate the relationship between the volume of joint effusion
      (JE), determined by T2-weighted magnetic resonance imaging (MRI), and microscopic
      findings of synovial inflammation in internal derangement of the
      temporomandibular joint (TMJ). STUDY DESIGN: Magnetic resonance images of 53
      symptomatic TMJs (53 patients) associated with painful hypomobility were taken to
      evaluate the degree of JE on a scale of 0 to 3. Within 2 months after MRI, biopsy
      specimens obtained by arthroscopy were quantitatively assessed, on the basis of
      Gynther's grading system, for severity of hyperplasia of synovial lining cell
      layers, vascularity, and the presence of inflammatory cells. Each synovitis score
      was compared among the 4 JE grades, as well as between 2 groups-effusion present
      (grades 2 and 3) and effusion absent (grades 0 and 1)-by using the Spearman
      correlation coefficiency and the Mann-Whitney U test. RESULTS: The distribution
      of JE was as follows: 14 joints had grade 0, 9 joints had grade 1, 19 joints had
      grade 2, and 11 joints had grade 3. Significant relationships were found between
      the grades of JE and scores of synovial lining cell layers (P =.0012) as well as
      between the grades of JE and scores of presence of inflammatory cells (P =.0064).
      The joints with effusion had significantly higher scores for synovial lining cell
      layers (2.0 +/- 0.2) than the joints without effusion (1.3 +/- 0.2) (P =.029).
      There was no statistically significant correlation between the scores of
      vascularity and JE (P =.394). CONCLUSIONS: The evidence of JE on MRI might
      correlate with synovial inflammatory activity. It confirms the common consensus
      that JE probably reflects synovitis, especially when synovial hyperplasia has a
      key role in the pathogenesis of JE.

PMID- 12789162
TI  - Human hair: a unique physicochemical composite.
AB  - All hair is ethnic. Categorizing diverse hair types into 3 major groups-African,
      Asian, and Caucasian-makes it easier to recognize characteristics specific to
      each hair type, such as curliness, color, and cross-sectional parameters. All
      hair, however, regardless of its ethnic origin, exhibits common characteristics
      of morphology, chemical makeup, and molecular structure. This article provides a
      brief review of the salient elements of hair structure, chemistry, and the
      fundamental interplay that contributes to the properties of the hair fiber and
      its response to treatments.

PMID- 12789163
TI  - Current research on ethnic hair.
AB  - This study collected qualitative and quantitative data about the morphology,
      structure, geometry, water swelling, and mechanical properties of hair fibers
      from subjects of different ethnic origins. X-ray analysis, cross-sectional
      measurements, tensile testing, and water swelling were performed on samples of
      hair collected from Caucasian, Asian, and African subjects. No differences in the
      intimate structures of fibers were observed among these 3 types of hairs, whereas
      geometry, mechanical properties, and water swelling differed according to ethnic
      origin. In addition, the behavior of hair fiber under mechanical stress was
      visualized with environmental scanning electron microscopy.

PMID- 12789164
TI  - Hair shape of curly hair.
AB  - The hair follicle is a unique composite organ, composed of epithelial and dermal
      compartments interacting with each other in a surprisingly autonomous way. This
      is a self-renewing organ that seems to be a true paradigm of epithelial and
      mesenchymal interactions. Each of the follicular compartments is endowed with a
      specific differentiation pathway under the control of an intricate network of
      growth factors, cytokines, and hormones. As observed for ethnic hairs, even the
      shape of the hair shaft is intrinsically programmed from the bulb.

PMID- 12789165
TI  - Ethnic hair update: past and present.
AB  - Hair and scalp disorders in African American patients are challenging because of
      the lack of pathophysiologic explanations for many of the disorders that occur in
      this population. To understand the clinical appearance of these disorders and to
      design an effective treatment plan, the dermatologist must have a clear knowledge
      of the basic hair-care practices and concerns of this group of patients. Given
      that patients of African American heritage are not a homogeneous group, this
      overview describes many of the common hair-care practices of African Americans
      and how they affect patients' health. The common hair and scalp disorders are
      discussed, with a specific focus on inflammatory disorders that result in
      significant pigmentation alteration or scarring.

PMID- 12789166
TI  - Lasers in ethnic skin: a review.
AB  - Laser therapy has been a mainstay of dermatologic therapy for more than a decade.
      However, until recently, most published literature focused on the Caucasian
      patient. The face of the aesthetic patient is changing to be more representative
      of the ethnic diversity of the population of the United States. It is imperative
      that the dermatologic surgeon not only have an understanding of the concerns of
      the aesthetic patient but also have an awareness of the unique needs of those
      with darker skin.

PMID- 12789167
TI  - Ethnic skin: overview of structure and function.
AB  - Racial variability in skin function is an area in which data often conflict.
      Understanding and quantifying racial differences in skin function are important
      for skin care and the prevention and treatment of skin diseases. A key feature
      that characterizes race is skin color: Is deeply pigmented skin different from
      fair skin in terms of responses to chemical and environmental insults? Is skin
      care the same? Are there different risks among racial groups of developing a skin
      disease after exposure to the same insults? The interpretation of
      pathophysiologic phenomena should consider not only anatomic and functional
      characteristics of ethnic groups but also socioeconomic, hygienic, and
      nutritional factors. This article reviews and discusses recent findings.

PMID- 12789168
TI  - Ethnic skin disorders overview.
AB  - With the changing demographics of the US population, there is a need to
      understand the variety of dermatologic disorders that manifest in ethnic groups
      of non-Caucasian skin types. This article provides a review of presentations and
      current treatments of several common dermatologic diagnoses in black, Hispanic,
      and Asian racial groups and compares them with the presentations in Caucasian
      skin. The specific diagnoses discussed in the different racial groups include
      acne; pigmentary disorders such as postinflammatory hyperpigmentation and
      hypopigmentation, vitiligo, and melasma; and photoaging. Because the majority of
      the world's population already consists of people with pigmented skin and the
      population within the United States is approximately one-third non-Caucasian,
      physicians who practice in the field of dermatology today need a thorough
      understanding of non-Caucasian dermatoses.

PMID- 12789169
TI  - Connections between psoriasis and Crohn's disease.
AB  - The prevalence of psoriasis in patients with Crohn's disease (CD) is higher than
      chance would allow if they were mutually exclusive diseases. A close examination
      reveals genetic and pathologic connections between these diseases. An
      appreciation for the role of tumor necrosis factor-alpha in both diseases has
      proven very important. Increased levels of this inflammatory cytokine have been
      measured in CD lesions, and in 1997 a clinical trial demonstrated the response of
      this disease to infliximab, a monoclonal antibody specific for tumor necrosis
      factor-alpha. A subsequent clinical trial evaluated infliximab in a patient with
      CD and psoriasis, another disease in which increased levels of tumor necrosis
      factor-alpha are seen in lesions. Scientists noticed the marked skin improvement
      of this patient and later demonstrated the efficacy of infliximab for psoriasis
      in a randomized, double-blind, placebo-controlled trial. Thus, an appreciation
      for connections between psoriasis and CD can suggest novel therapeutic strategies
      with ensuing benefits to patients. This article reviews epidemiologic, genetic,
      and pathologic connections between psoriasis and CD and discusses pharmaceuticals
      targeting inflammatory mediators common to each disease. (J Am Acad Dermatol
      2003;48:805-21.) LEARNING OBJECTIVE: At the completion of this learning activity,
      participants should understand how psoriasis and Crohn's disease are related at
      epidemiologic, genetic, and pathological levels and should appreciate how to use
      this knowledge to treat these diseases.

PMID- 12789170
TI  - Brachioradial pruritus: a symptom of neuropathy.
AB  - BACKGROUND: Brachioradial pruritus (BRP) is a localized pruritus of the
      dorsolateral aspect of the arm. BRP is an enigmatic condition with a
      controversial cause; some authors consider BRP to be a photodermatosis whereas
      other authors attribute BRP to compression of cervical nerve roots. OBJECTIVE: We
      sought to investigate the presence of neuropathy in patients with BRP. METHODS:
      We performed electrophysiologic studies of the median, ulnar, and radial nerves
      in consecutive patients with BRP, including measurement of sensory and motor
      distal latency, conduction velocity and F responses of the median and ulnar
      nerves, and sensory distal latency of the radial nerves in both upper limbs.
      RESULTS: Included in the study were 7 patients, 5 men and 2 women, with an
      average age of 58.3 years (range: 42-72 years). Of the patients, 4 (57%) had
      abnormal F responses that were diagnostic for cervical radiculopathy, and 3 of
      these patients had prolonged distal latencies of the nerves tested, which may be
      interpreted as sensory motor neuropathy secondary to chronic radiculopathy. The
      fourth patient had polyneuropathy secondary to diabetes mellitus. CONCLUSION: BRP
      may be attributed to a neuropathy, such as chronic cervical radiculopathy. The
      possibility of an underlying neuropathy should be considered in the evaluation
      and treatment of all patients with BRP.

PMID- 12789171
TI  - Infliximab monotherapy provides rapid and sustained benefit for plaque-type
      psoriasis.
AB  - BACKGROUND: Effective, rapid-acting, safe therapies are needed for the long-term
      treatment of psoriasis. OBJECTIVE: We sought to evaluate infliximab monotherapy
      in maintaining clinical benefit in psoriasis. METHODS: A total of 33 patients
      received 3 doses of 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6
      (double-blind phase). During the open-label phase (weeks 10-26), responding
      patients were evaluated for relapse (loss of at least half of the improvement in
      the Psoriasis Area Severity Index score at week 10) and retreated with open-label
      infliximab (5 or 10 mg/kg) as needed. Placebo nonresponders were treated with an
      induction regimen of infliximab (5 or 10 mg/kg) and followed up through week 26.
      RESULTS: In all, 29 patients received either 5 or 10 mg/kg of infliximab in the
      open-label extension. At week 26, psoriasis area severity index response was
      maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab,
      respectively. CONCLUSION: Infliximab produced a rapid, effective, and sustainable
      (through week 26) effect in patients with moderate to severe psoriasis.

PMID- 12789173
TI  - Mid-dermal elastolysis: a clinical, histologic, and immunohistochemical study of
      11 patients.
AB  - BACKGROUND: Mid-dermal elastolysis is a rare entity defined by the selective loss
      of elastic tissue in the mid dermis. Many cases appear induced or aggravated by
      ultraviolet (UV) light exposure. Pathogenesis is still uncertain. OBJECTIVE: Our
      purpose was to report on the clinical and histologic features of 11 patients with
      mid-dermal elastolysis. Moreover, we analyzed by immunohistochemistry leukocyte
      subsets and expression of metalloproteinase (MMP) with the potential to degrade
      elastic tissue in 7 cases. RESULTS: All patients were women with a mean age of
      31.4 years. Disease duration ranged from 4 months to 17 years. Affected areas
      included the trunk, neck, and upper aspect of limbs. Two patients also had
      Hashimoto's thyroiditis and uterine carcinoma, respectively, whereas 1 patient
      had undergone silicone mammoplasty. In all patients, disease onset was associated
      with intense UV light exposure. Moderate leukocyte infiltration in the dermis was
      observed mostly in recent lesions and was composed of CD3(+) T cells and some
      CD68(+) macrophages with a normal number of factor XIIIa(+) dermal dendritic
      cells. Elastin, but not fibrillin-1 immunoreactivity disappeared from the mid
      dermis. MMP-9 was detected in epidermal keratinocytes and in the cytoplasm of
      large, angulated, multinucleated cells located in lesional dermis. These cells
      were negative for leukocyte, dendritic cell, macrophage, and T-cell markers and
      were absent in old lesions. Staining for MMP-7 and MMP-12 did not differ from
      control skin. CONCLUSION: Onset of mid-dermal elastolysis appears strongly
      associated with UV exposure, which may induce fibroblast-like cells to express
      MMP-9 that in turn could be involved in the degradation of elastic fibers.

PMID- 12789172
TI  - Efficacy and safety of azelaic acid (15%) gel as a new treatment for
      papulopustular rosacea: results from two vehicle-controlled, randomized phase III
      studies.
AB  - BACKGROUND: Rosacea is a common, chronic dermatosis for which safe and effective
      new treatment options are needed. OBJECTIVE: The objective of these studies was
      to evaluate the efficacy, tolerability, and safety of a new formulation of 15%
      azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate,
      papulopustular rosacea. METHODS: Two multicenter, double-blind, randomized,
      parallel-group, vehicle-controlled studies were conducted using identical study
      designs, patient-selection criteria, and efficacy end points. Overall, 329
      patients were enrolled in study 1 and 335 patients in study 2. RESULTS: Both
      studies consistently demonstrated the superiority of AzA gel over vehicle in the
      topical treatment of moderate, papulopustular rosacea. AzA gel yielded
      statistically significantly higher reductions in mean inflammatory lesion count
      than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P
      =.0208). Significantly higher proportions of patients treated with AzA gel
      experienced improvement in erythema compared with vehicle gel: 44% versus 29%,
      study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's
      global assessment, therapeutic success in terms of a clear, minimal, or mild
      final result was achieved in 61% and 62% of patients treated with AzA gel in
      studies 1 and 2, respectively, which was significantly superior to the result
      achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127,
      study 2). No serious, treatment-related adverse events were reported. CONCLUSION:
      The results of these 2 controlled studies demonstrate that AzA gel, used twice
      daily, is an efficacious, safe, and well-tolerated topical treatment for
      moderate, papulopustular rosacea.

PMID- 12789174
TI  - Scytalidiosis in Paris, France.
AB  - BACKGROUND: Scytalidium dimidiatum and S hyalinum are molds responsible for human
      skin and nail infections in tropical areas. OBJECTIVE: We sought to examine the
      epidemiology of cutaneous infections caused by Scytalidium species in a temperate
      country. METHODS: We conducted a retrospective study of patients with Scytalidium
      spp. infection diagnosed in our laboratory in Paris, France, from 1994 to 1999.
      RESULTS: Cutaneous Scytalidium infections were diagnosed in 332 patients, all of
      whom were from the tropics, especially the West Indies and Africa. S hyalinum and
      S dimidiatum were isolated in 53.6% and 43.9% of cases, respectively, and were
      associated with dermatophytes in 30 patients. Skin and nail lesions were found
      in, respectively, 65.3% and 34.7% of cases, and the feet were involved in 90.6%
      of cases. CONCLUSION: Cutaneous infections caused by Scytalidium species are far
      from rare in France, a temperate country, and must not be mistaken for
      dermatophytosis, given the resistance of S hyalinum and S dimidiatum to most
      antifungal drugs. Mycologic examination is, thus, required to identify
      Scytalidium spp in patients returning from or residing in tropical areas.

PMID- 12789175
TI  - Species identification and strain differentiation of dermatophyte fungi using
      polymerase chain reaction amplification and restriction enzyme analysis.
AB  - BACKGROUND: Standard biochemical tests, microscopy, colony characteristics, and
      mating tests have conventionally been used for the identification of
      dermatophytes species, but these methods of identification are costly, time
      consuming, and require special skills. OBJECTIVE: Our purpose was to identify a
      method that enables rapid species identification and strain differentiation of
      dermatophyte fungi. METHODS: We chose 4 restriction enzymes (BsYiI, DdeI, HinfI,
      and MvaI) that could produce different fragment patterns after enzyme digestion
      according to species or strain. We performed enzyme digestions after polymerase
      chain reaction amplification of internal transcribed spacer region and identified
      different restriction fragment length polymorphisms (RFLP) according to species
      and strains. RESULTS: All the species included in this study could be easily
      differentiated using any combination of 2 different restriction enzymes except
      Trichophyton rubrum and T raubitschekii, which produced identical digestion
      patterns after all 4 restriction enzyme digestions. In the case of T
      mentagrophytes, MvaI and DdeI each produced 2 distinct RFLP patterns. CONCLUSION:
      This study showed that internal transcribed spacer region analysis using
      polymerase chain reaction-RFLP through DdeI and MvaI is useful for rapid
      identification of the majority of dermatophytes species. However, there were 2
      different band patterns by DdeI and MvaI restriction enzyme digestion and no
      correlations between morphologic types and RFLP patterns in T mentagrophytes.

PMID- 12789176
TI  - UV photoprotection by combination topical antioxidants vitamin C and vitamin E.
AB  - BACKGROUND: Virtually all plants and animals protect themselves from the sun
      using vitamins C and E. OBJECTIVE: The purpose of this study was to see if a
      combination of topical vitamins C and E is better for UV protection to skin than
      an equivalent concentration of topical vitamin C or E alone. METHODS: We
      developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1%
      alpha-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig
      skin daily for 4 days. We irradiated (1-5x minimal erythema dose) control- and
      antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter.
      On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and
      thymine dimers. RESULTS: The combination of 15% L-ascorbic acid and 1% alpha
      tocopherol provided significant protection against erythema and sunburn cell
      formation; either L-ascorbic acid or 1% alpha-tocopherol alone also was
      protective but the combination was superior. Application during 4 days provided
      progressive protection that yielded an antioxidant protection factor of 4-fold.
      In addition, the combination of vitamins C and E provided protection against
      thymine dimer formation. CONCLUSION: Appreciable photoprotection can be obtained
      from the combination of topical vitamins C and E. We suggest that these natural
      products may protect against skin cancer and photoaging.

PMID- 12789177
TI  - Reduction in injection pain with botulinum toxin type B further diluted using
      saline with preservative: a double-blind, randomized controlled trial.
AB  - BACKGROUND: Injection with botulinum A exotoxin reconstituted with preserved
      saline has been shown to be less uncomfortable than injection with the same toxin
      reconstituted with preservative-free saline. OBJECTIVE: We sought to determine
      whether injection with botulinum toxin type B is similarly less painful when
      preservative-containing saline is used to further dilute the product. METHODS: We
      conducted a double-blind, randomized controlled trial. A total of 15 consecutive
      adult patients presenting for treatment of upper face dynamic lines received
      treatment to one side (left or right) of the face with toxin type B further
      diluted with preservative-containing saline, and to the other side with toxin
      type B further diluted with preservative-free saline. RESULTS: Of 15 patients, 13
      (87%) reported less pain in the halves of their faces treated with the
      preservative-containing saline (P =.0006). Pain on the preservative-containing
      side was on average 32% less among patients as a whole, and 39% less among
      patients noting some reduction. The 95% confidence interval for pain reduction
      associated with preservative-containing injection was -46.9% to -16.1%. Neither
      investigators nor patients observed any difference in clinical efficacy between
      the 2 treatment sides. CONCLUSIONS: Use of preservative-containing saline to
      further dilute botulinum toxin type B can significantly decrease patient
      discomfort on injection.

PMID- 12789178
TI  - Cutaneous lesions of secondary syphilis are highly angiogenic.
AB  - BACKGROUND: The role of angiogenesis in infectious processes is poorly studied.
      Some viruses have been linked to angiogenesis, but the role of bacteria and
      protozoa in inducing angiogenesis in chronic infections is poorly understood.
      OBJECTIVES: We examined the role of angiogenesis in syphilis, a common and often
      difficult-to-treat infectious disease, especially in the setting of HIV/AIDS.
      METHOD: Microvessel counts were performed on 27 paraffin-fixed sections of
      secondary syphilis by staining with monoclonal antibodies against CD31. In
      addition, immunohistochemistry was performed using antibodies against vascular
      endothelial growth factor (VEGF) to determine whether increased angiogenesis may
      be mediated, in part, through increased production of VEGF. RESULTS: The CD31
      mean microvessel count in secondary syphilis sections was significantly higher
      than in normal control sections. VEGF intensity appeared increased in the
      patients with secondary syphilis. CONCLUSIONS: Infection with Treponema pallidum
      results in increased angiogenesis in secondary syphilis. The mechanism for
      increased angiogenesis may involve elaboration of angiogenic cytokines, such as
      VEGF and epidermal growth factor.

PMID- 12789179
TI  - Lipid profile, insulin secretion, and insulin sensitivity in psoriasis.
AB  - BACKGROUND: Psoriasis has been associated with an abnormal plasma lipid
      metabolism and diabetes mellitus possibly related to alterations in insulin
      secretion and sensitivity. OBJECTIVE: We sought to identify lipid profile,
      insulin secretion, and insulin sensitivity in patients with psoriasis and healthy
      control patients. METHODS: A cross-sectional study was performed in 44 nonobese
      adults, 22 with psoriasis and 22 without. The psoriasis activity was evaluated by
      the psoriasis area and severity index. Insulin secretion was estimated using the
      homeostasis model analysis beta-cell function index. Insulin sensitivity was
      assessed with the insulin tolerance test. RESULTS: High-density lipoprotein
      cholesterol was significantly decreased in patients with psoriasis (P =.02).
      There were no significant differences in insulin secretion or sensitivity in
      patients with psoriasis compared with control patients. CONCLUSION: Patients with
      psoriasis had significantly decreased high-density lipoprotein cholesterol
      concentrations. There were no differences in insulin secretion or sensitivity
      compared with control patients.

PMID- 12789180
TI  - Graftskin therapy in epidermolysis bullosa.
AB  - BACKGROUND: Epidermolysis bullosa (EB) is a family of 23 genetic skin disorders
      for which treatments are mainly supportive. Graftskin is a bilayered living human
      skin construct characterized by a normal expression profile of all the genes
      reported as mutant in EB. OBJECTIVE: The objective of this study was to evaluate
      the efficiency and durability of graftskin in the treatment of EB. METHODS: A
      total of 9 children with EB were treated with graftskin. These include EB
      simplex: Dowling-Meara type (n = 2); Weber-Cockayne type (n = 1); junctional EB
      Herlitz type (n = 1); and recessive dystrophic EB (n = 5). Lesions were debrided
      of epidermis and crusts followed by application of fenestrated graftskin under
      sterile conditions. Syndactyly hand release for "mitten deformity" was performed
      after removal of all epidermis under general anesthesia. All treatment sites were
      dressed with a nonadherent contact layer followed by absorbent foam dressing,
      roll gauze, and a compression wrap covering and were left intact for 1 week.
      Graft take was assessed clinically at weeks 1, 2, 4, 12, and 20 to 28. Graft
      persistence was assessed by electron microscopy and polymerase chain reaction
      analysis at weeks 4 and 12, and between weeks 20 and 28 on selected cases.
      RESULTS: A total of 96 sites were treated with 90% to 100% healing observed by 5
      to 7 days, and many sites appearing as normal skin by 10 to 14 days. Finger and
      hand lesions showed 50% to 90% improvement in range of motion over baseline. Two
      children learned to walk after graftskin treatment of chronic plantar lesions.
      Two children had improvement in their chronic anemia after graftskin treatment.
      All patients and/or parents reported rapid pain resolution. Immunologic and
      genetic studies of graft persistence revealed evidence of donor DNA up to 28
      weeks after graftskin application. None of the samples from female patients
      demonstrated Y chromosome-specific sequence when analyzed by the method of short
      tandem repeat. CONCLUSION: The encouraging results reported herein support the
      hypothesis that graftskin is more than a simple bandage or a source of growth
      factors to stimulate autologous closure of EB wounds. The improved quality of
      life and rapid achievement of growth/development milestones we have observed
      makes this an exciting step forward in the care of the patient with EB.

PMID- 12789182
TI  - Effectiveness of dermasanding (manual dermabrasion) on the appearance of surgical
      scars: a prospective, randomized, blinded study.
AB  - BACKGROUND: Dermasanding using sterile sandpaper has been described as a simple
      treatment for scars but has not been evaluated in a prospective randomized
      fashion. It could provide a safe, simple, and cost-effective option for the
      treatment of scars. OBJECTIVE: Our purpose was to assess the effectiveness of
      dermasanding on the appearance of surgical scars of the face. METHODS: We
      evaluated 15 patients using a blinded, split-scar model. Each scar was divided
      into 2 equal portions, and half of the scar was treated according to randomized
      assignment. Scars were treated with dermasanding 6 to 8 weeks after operation.
      The treatment half was compared with the control half by blinded observers at 3
      time points. RESULTS: Improvement in the treated half of scars was seen in 80% of
      patients at 6 months (95% confidence interval, 60%-100%), and 47% had an
      excellent response. In 20% of patients the unsanded side was better. CONCLUSIONS:
      Dermasanding is an effective procedure in the treatment of surgical scars.

PMID- 12789181
TI  - Treatment of cutaneous leishmaniasis by photodynamic therapy.
AB  - BACKGROUND: Cutaneous leishmaniasis represents a common health problem and
      standard treatments are often ineffective or yield poor cosmetic results.
      OBJECTIVE: We compared the efficacy of photodynamic therapy (PDT) with
      paromomycin sulfate in 10 lesions of cutaneous leishmaniasis. METHODS: Five
      lesions were treated by PDT with Metvix (Photocure, Oslo, Norway) and 75 J/cm(2)
      red light. PDT was performed twice weekly and, after 12 weeks, once weekly. The
      other 5 lesions were treated with paromomycin sulfate once daily. All
      nonresponding lesions of the paromomycin-treated plaques finally also underwent
      PDT. RESULTS: All 5 lesions treated by PDT and 2 of the paromomycin sulfate
      treated plaques were clinically and histologically Leishmania free. Three lesions
      with poor response to paromomycin sulfate finally responded to subsequent PDT.
      Ten months after therapy there was no recurrence, and cosmetic outcome after PDT
      was excellent. CONCLUSION: PDT may be an effective therapeutic alternative in
      cutaneous leishmaniasis.

PMID- 12789183
TI  - Histopathologic findings in lupus erythematosus tumidus: review of 80 patients.
AB  - BACKGROUND: In a recent study, we demonstrated that lupus erythematosus (LE)
      tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically
      characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed
      areas. OBJECTIVE: Our purpose was to analyze skin biopsy specimens from 80
      patients with this disease and to determine whether it could be differentiated
      from other variants of CLE on histopathologic grounds. METHODS: Skin biopsy
      specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients
      with LET were examined and compared with skin biopsy specimens from patients with
      discoid LE (DLE) and subacute CLE (SCLE). RESULTS: Specimens from LET lesions
      showed a characteristic and diagnostic pattern of perivascular and periadnexal
      cellular infiltrates in the papillary and reticular dermis composed almost
      entirely of lymphocytes. In some cases, few scattered neutrophils were present.
      Furthermore, interstitial mucin deposition was observed in all specimens, as
      confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE
      lesions, epidermal atrophy or alteration at the dermoepidermal junction was not
      detected. CONCLUSION: Skin lesions of patients with LET present with specific
      histopathologic features, and the differences compared with subacute CLE and
      discoid LE further support the concept to consider LET as a separate entity of
      CLE.

PMID- 12789184
TI  - The evolution of current medical and popular attitudes toward ultraviolet light
      exposure: part 2.
AB  - The 1920s and 1930s represented an extraordinary time in the shaping of modern
      attitudes towards ultraviolet light. Dermatologists and other physicians today
      are still confronting the effects of changes in social behavior that occurred at
      this time. The discovery that ultraviolet wavelengths played a role in vitamin D
      synthesis in the skin ushered in a period of enormous popularity for ultraviolet
      light exposure. A variety of other medical claims were soon made for ultraviolet
      radiation, including that it increased resistance to disease. The field of
      phototherapy rapidly expanded, and its use was employed by proponents for a host
      of unlikely medical conditions. Exposure to sunlight or ultraviolet lamps was
      widely promoted as a form of preventive medicine. Home sunlamps gained popularity
      and were aggressively marketed to the public. A suntan, which had previously
      achieved limited popularity, now was viewed as de rigueur in the United States
      and Europe. The role that medical advocacy of ultraviolet light exposure played
      in initially advancing the practice of sunbathing is not commonly appreciated
      today. Ironically, public health recommendations of the time were often
      diametrically opposed to those being made at present, since sunlight exposure is
      currently recognized as the major preventable cause of cancer of the skin.

PMID- 12789185
TI  - Bibliographic landmarks in the history of dermatology.
AB  - The current advancements in our understanding of cutaneous diseases should not
      obscure our appreciation for the past and the achievements of the founders of
      dermatology. Their observations, ideas, discoveries, and writings shaped the
      development of the specialty, influence daily practices today, and serve as the
      foundation for future research endeavors. This article reviews the history of
      outstanding contributions that were preserved in enduring landmark works on which
      the whole knowledge of skin diseases rests. From the earliest books written with
      meager prior information to the impressive 19th century texts and atlases
      providing significant advances, these volumes marked and recorded defining
      moments in the evolution of dermatology.

PMID- 12789186
TI  - Surgical pearl: use of the vacutainer as a closed, active, surgical drain.

PMID- 12789188
TI  - Diffuse neurofibroma on the lower back.
AB  - Diffuse neurofibroma is an uncommon form of neurofibroma, which occurs
      principally in children and young adults. This tumor presents most often in the
      head and neck region. We have seen a young girl with a diffuse neurofibroma on
      the lower back that was successfully excised.

PMID- 12789187
TI  - Tacrolimus ointment for the treatment of vulvar lichen sclerosus.
AB  - The treatment of vulvar lichen sclerosus is generally considered difficult.
      Ultrapotent corticosteroids represent the most effective topical treatment, but
      carry the risk of side effects such as skin atrophy. We describe a 71-year-old
      woman with long-standing vulvar lichen sclerosus refractory to conventional
      treatment. After 6 consecutive weeks of treatment with tacrolimus ointment 0.1%
      (Protopic) twice daily, signs and symptoms of lichen sclerosus resolved. To our
      knowledge, this is the first report of the use of topical tacrolimus, which does
      not induce skin atrophy, in the treatment of vulvar lichen sclerosus.

PMID- 12789189
TI  - Papular-purpuric "gloves and socks" syndrome in a mother and daughter.
AB  - The papular-purpuric "gloves and socks" syndrome (PPGSS) is a unique exanthem
      characterized by petechiae with painful edema of the hands and feet extending
      proximally with less severity. Constitutional symptoms of fever, lethargy, and
      arthralgia have also been described. Human parvovirus B19 has been implicated in
      most cases as the causative agent. We describe a mother and her daughter
      presenting with the characteristic findings of PPGSS and demonstrating the
      seroconversion of human parvovirus B19 a few days after the onset of their
      illness. Additional clinical findings of cutaneous vesicles, bullae, and
      conjunctivitis are reported in the mother's case. To our knowledge, these are the
      first 2 cases of PPGSS in a household setting.

PMID- 12789190
TI  - Superficial gyrate erythema as a cutaneous reaction to alendronate for
      osteoporosis.
AB  - Alendronate is a bisphosphonate compound used to treat diseases of pathologic
      bone resorption. Cutaneous reactions to this medication are rare. We report the
      case of a superficial gyrate erythema that occurred as a reaction to weekly
      alendronate therapy used in the treatment of postmenopausal osteoporosis.

PMID- 12789191
TI  - Severe subacute cutaneous lupus erythematosus presenting with generalized
      erythroderma and bullae.
AB  - A 31-year-old woman presented with progressive generalized erythroderma and
      bullae. Histologic evaluation revealed dyskeratosis and interface dermatitis with
      a paucity of infiltrate. Serologic evaluation revealed markedly elevated titer of
      Ro/SS-A and La/SS-B antibodies. Further workup revealed leukopenia. The
      generalized eruption cleared with prednisone. The patient later had the classic
      discrete lesions of subacute cutaneous lupus erythematosus develop. The
      erythrodermic and bullous presentation of subacute cutaneous lupus erythematosus
      is rare and requires a high index of suspicion.

PMID- 12789192
TI  - Cutis marmorata telangiectatica congenita with hemangiomatous histopathologic
      features.
AB  - Cutis marmorata telangiectatica congenita (CMTC) is a congenital cutaneous
      vascular malformation that is diagnosed on the typical clinical findings of
      persistent cutis marmorata, telangiectasia, phlebectasia, occasional ulceration
      and atrophy, and tendency for clinical improvement. Histopathologic findings
      seldom have been reported. We report a case of CMTC with atypical histopathologic
      findings of proliferation of vasculature in addition to dilated capillaries in
      the dermis. We have reviewed all cases of CMTC with histopathologic findings
      published in the English-language literature. The most common and prominent
      finding was dilation of capillaries and veins in the dermis (13/15 cases). Two
      cases, including our own, demonstrated proliferation of vascular channels. The
      implications of vascular proliferation on the clinical course of CMTC are
      unclear.

PMID- 12789193
TI  - Unilateral Darier's disease with unilateral guttate leukoderma.
AB  - We report a case of diffuse unilateral Darier's disease that is associated with
      unilateral macular hypopigmentation. The histologic evidence of the hypopigmented
      macules revealed features of Darier's disease.

PMID- 12789194
TI  - Fatal Lucio's phenomenon in 2 patients with previously undiagnosed leprosy.
AB  - We report 2 cases of Lucio's phenomenon, a rare, aggressive, occasionally fatal
      type 2 reaction occurring in the diffuse nonnodular type of lepromatous leprosy.
      The clinical diagnosis of Lucio's phenomenon is difficult, and there are no known
      predictive or prognostic factors. Despite institution of aggressive treatment
      after diagnosis, our 2 cases had fatal outcomes.

PMID- 12789195
TI  - Pseudoacromegaly induced by the long-term use of minoxidil.
AB  - Acromegaly is an endocrine disorder caused by chronic excessive growth hormone
      secretion from the anterior pituitary gland. Significant disfiguring changes
      occur as a result of bone, cartilage, and soft tissue hypertrophy, including the
      thickening of the skin, coarsening of facial features, and cutis verticis gyrata.
      Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid
      features in the absence of elevated growth hormone or insulin-like growth factor
      levels. We present a patient with pseudoacromegaly that resulted from the long
      term use of minoxidil at an unusually high dose. This is the first case report of
      pseudoacromegaly as a side effect of minoxidil use.

PMID- 12789196
TI  - Culture and immunohistochemical evidence of Chlamydia pneumoniae infection in
      ulcerative pyoderma gangrenosum.
AB  - A potentially contributing factor to the development and chronicity of pyoderma
      gangrenosum is infection with the relatively recently characterized human
      pathogen, Chlamydia pneumoniae. C pneumoniae is an obligate intracellular
      bacterium that can infect endothelial, monocyte, and smooth muscle cells and is
      associated with cardiopulmonary diseases. A case of serologically, polymerase
      chain reaction-positive, immunohistochemically, and culture-documented viable C
      pneumoniae organisms in a chronic pyoderma gangrenosum ulcer is reported, a
      finding that has not been described previously.

PMID- 12789197
TI  - Triad of exophthalmos, pretibial myxedema, and acropachy in a patient with
      Graves' disease.
AB  - Graves' disease is an autoimmune disorder of the thyroid gland with
      characteristic peripheral manifestations. The most common clinical findings
      include ophthalmopathy in 30% of patients, dermopathy (pretibial myxedema) in 4%
      of patients, and thyroid acropachy in 1% of patients. The triad of exophthalmos,
      pretibial myxedema, and acropachy occurs in less than 1% of patients. We present
      a case of Graves' disease with the clinical triad of eye disease, dermopathy, and
      acropachy.

PMID- 12789198
TI  - Erythromelalgia precipitated by acral erythema in the setting of
      thrombocytopenia.
AB  - Erythromelalgia is a rare syndrome that is characterized by episodic attacks of
      burning pain in the distal extremities, which last from minutes to days and are
      precipitated by exercise, warmth, or limb dependency. There is a primary or
      idiopathic form and a secondary form that occur with myeloproliferative or other
      diseases. All previous reports about erythromelalgia that is the result of a
      myeloproliferative process have documented associated thrombocytosis. We describe
      a 40-year-old woman with myelodysplastic syndrome who experienced erythromelalgia
      in the setting of acral erythema and thrombocytopenia, first induced by
      chemotherapy and recurring after a radiation- and chemotherapy-based
      myeloablative regimen that was administered before a T-cell-depleted allogeneic
      bone marrow transplantation.

PMID- 12789199
TI  - Antibodies to desmoglein 1 and 3, and the clinical phenotype of pemphigus
      vulgaris.

PMID- 12789200
TI  - AAD Guidelines of Care: how did we get here and where are we going?
AB  - In 1987 the American Academy of Dermatology began to create Guidelines of Care
      for clinical disease processes in dermatology. The format of the guidelines has
      changed dramatically over the past several years; now all of the recent
      guidelines are in the evidence-based style. These guidelines have been recognized
      nationally both in print and on the World Wide Web, establishing dermatologists
      as the skin experts. We believe that these guidelines continue to serve as
      effective educational tools for dermatologists around the world.

PMID- 12789201
TI  - Chloroquine-induced, vitiligo-like depigmentation.

PMID- 12789202
TI  - Merkel cell carcinoma after postmastectomy lymphedema.

PMID- 12789203
TI  - The hand-held dermatoscope improves the clinical evaluation of port-wine stains.

PMID- 12789204
TI  - Cutaneous manifestations of antiviral therapy.

PMID- 12789205
TI  - Vulvar itching in prepubertal girls: let's be specific.

PMID- 12789212
TI  - Rhinitis and asthma: evidence for respiratory system integration.
AB  - The vast majority of patients with asthma have rhinitis, and rhinitis is a major
      independent risk factor for asthma in cross-sectional and longitudinal studies.
      The relationships between rhinitis and asthma can be viewed under the concept
      that the 2 conditions are manifestations of one syndrome, the chronic allergic
      respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the
      syndrome's severity spectrum, rhinitis appears to be the sole manifestation,
      although pathologic abnormalities in the lower airways are already present. At
      the higher end, rhinitis is worse, and the lower airways disease becomes
      clinically evident. Once manifested, the 2 conditions track in parallel in terms
      of severity. This parallel relationship is influenced by many interactions
      between the nasal and the lower airways: some interactions stem from the fact
      that the nasal passages play a major homeostatic role by conditioning inhaled
      air, but perhaps even more important is the bidirectional interaction that
      results from the systemic inflammation that is produced after local allergic
      reactions. Successful management of the chronic allergic respiratory syndrome
      requires an integrated view of the airways and an understanding of their
      interactions.

PMID- 12789214
TI  - Chemokines: roles in leukocyte development, trafficking, and effector function.
AB  - Chemokines, representing a large superfamily of 8- to 15-kd proteins, were
      originally discovered through their ability to recruit various cell types into
      sites of inflammation. It is now clear that these molecules play a much wider
      role in immune homeostasis, playing key roles in driving the maturation, homing,
      and activation of leukocytes. In this review we analyze the roles chemokines play
      in the development, recruitment, and activation of leukocytes. Because signaling
      from the receptors drives these processes, signal transduction from chemokine
      receptors will also be reviewed. Taken together, we highlight the various points
      at which chemokines contribute to allergic inflammation and at which their
      targeting might contribute to new therapies for type I hypersensitivity
      reactions.

PMID- 12789216
TI  - Polarized helium: changing our view of asthma.

PMID- 12789217
TI  - Assessing the economic burden of asthma.

PMID- 12789218
TI  - Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic
      resonance: assessment of response to methacholine and exercise challenge.
AB  - BACKGROUND: Imaging of gas distribution in the lungs of patients with asthma has
      been restricted because of the lack of a suitable gaseous contrast agent.
      Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance
      imaging of lung diseases. OBJECTIVE: We sought to investigate the use of HHe3 gas
      to image the lungs of patients with moderate or severe asthma and to assess
      changes in gas distribution after methacholine and exercise challenge. METHODS:
      Magnetic resonance imaging was performed in asthmatic patients immediately after
      inhalation of HHe3 gas. In addition, images were obtained before and after
      methacholine challenge and a standard exercise test. RESULTS: Areas of the lung
      with no signal or sharply reduced HHe3 signal (ventilation defects) are common in
      patients with asthma, and the number of defects was inversely related to the
      percent predicted FEV(1) (r = 0.71, P <.002). After methacholine challenge (n =
      3), the number of defects increased. Similarly, imaging of the lungs after
      exercise (n = 6) showed increased ventilation defects in parallel with decreases
      in FEV(1). The increase in defects after challenge in these 9 asthmatic patients
      was significant both for the number (P <.02) and extent (P <.02) of the defects.
      The variability and speed of changes in ventilation and the complete lack of
      signal in many areas is in keeping with a model in which the defects result from
      airway closure. CONCLUSION: HHe3 magnetic resonance provides a new technique for
      imaging the distribution of inhaled air in the lungs. The technique is suitable
      for following responses to treatment of asthma and changes after methacholine or
      exercise challenge.

PMID- 12789219
TI  - A comprehensive study of the direct and indirect costs of adult asthma.
AB  - BACKGROUND: Asthma is a common and costly health condition, but most estimates of
      its economic effect have relied on secondary sources with limited condition
      specific detail. OBJECTIVE: We sought to estimate the magnitude of direct and
      indirect costs of adult asthma from the perspective of society. METHODS: We used
      cross-sectional survey data from an ongoing community-based panel study of 401
      adults with asthma originally derived from random samples of northern California
      pulmonologists, allergist-immunologists, and family practitioners to assess
      health care use for asthma, to assess purchase of items to assist with asthma
      care, and to measure work and other productivity losses. Unit costs derived from
      public-use and proprietary data sources were then assigned to the survey items.
      RESULTS: Total per-person annual costs of asthma averaged $4912 US dollars, with
      direct and indirect costs accounting for $3180 US dollars (65%) and $1732 US
      dollars (35%), respectively. The largest components within direct costs were
      pharmaceuticals ($1605 US dollars [50%]), hospital admissions ($463 US
      dollars[15%]), and non-emergency department ambulatory visits ($342 US dollars
      [11%]). Within indirect costs, total cessation of work accounted for $1062 US
      dollars (61%), and the loss of entire work days among those remaining employed
      accounted for another $486 US dollars (28%). Total per-person costs were $2646,
      $4530, and $12,813 US dollars for persons self-reporting mild, moderate, and
      severe asthma, respectively (P <.0001, 1-way ANOVA). CONCLUSION: Asthma-related
      costs are substantial and are driven largely by pharmaceuticals and work loss.

PMID- 12789220
TI  - Modifiable barriers to adherence to inhaled steroids among adults with asthma:
      it's not just black and white.
AB  - BACKGROUND: Sociobehavioral factors influence adherence to inhaled corticosteroid
      (ICS) in adults with asthma and warrant exploration as explanations of apparent
      racial disparities in adherence. OBJECTIVE: The purposes of this study were to
      identify barriers to adherence, potentially modifiable by healthcare providers,
      in a group of African Americans and non-African Americans and to test modifiable
      barriers as explanations of racial-ethnic differences in adherence. METHODS: We
      conducted a cohort study of 85 adults (mean age, 47 +/- 15 years; 61 [72%]
      female; 55 [65%] African American) with moderate or severe persistent asthma to
      determine modifiable sociobehavioral predictors of adherence. These were
      knowledge of the function of ICS, patient-perceived adequacy of communication
      with the provider, social support, attitude (perception of risks/benefits of
      ICS), depression, and self-efficacy. Adherence was calculated from electronic
      monitoring data as the mean of the number of doses recorded per 12 hours divided
      by the number prescribed, truncated at 100%. Past adherence, baseline severity of
      symptoms, and sociodemographics were treated as fixed confounders in ordinal
      logistic modeling. RESULTS: Adherence was 60% +/- 30%. In bivariate analyses,
      favorable attitude to ICS (P =.01) was associated with better adherence. Of
      immutable predictors, African American race-ethnicity (P =.001), lower
      educational achievement (P =.01), lower household income (P =.002), and more
      baseline symptoms (P =.003) were associated with poorer adherence. In
      multivariable analysis, controlling for immutable predictors, favorable attitude
      was associated with adherence. Favorable attitude was associated with greater
      adherence in African Americans and non-African Americans. Controlling for
      immutable factors, the race-adherence relationship was not mediated by the
      mutable factors, but economic factors (income and insurance) were mediators.
      CONCLUSION: Attitude is strongly related to adherence but does not mediate the
      effect of race-ethnicity.

PMID- 12789221
TI  - Smallpox vaccination and risk of allergy and asthma.
AB  - BACKGROUND: It has been proposed that childhood vaccinations may influence the
      development of allergy. Atopy and allergic diseases have increased after routine
      smallpox vaccination was stopped in the 1970s. OBJECTIVE: We examined whether
      administration of smallpox vaccination during childhood was associated with a
      decreased risk of atopy, allergic rhinitis, and asthma. METHODS: The occurrence
      of atopy, allergic rhinitis, and asthma was studied in nearly 2000 women
      participating in a national birth cohort study. Detailed information on smallpox
      vaccination was available from school health records. Atopic status was assessed
      serologically by a specific response to 11 common inhalant allergens by using
      serum samples obtained from the women during the period 1997 to 2001. Information
      on allergic rhinitis and asthma was available from telephone interviews. RESULTS:
      We found no association between having been vaccinated against smallpox in
      childhood and risk of atopy or allergic rhinitis. Smallpox vaccination was
      associated with a slightly decreased risk of asthma. There was no association
      between age at smallpox vaccination and risk of atopy, allergic rhinitis, or
      asthma. Adjusting for birth cohort, sibship size, age of the woman's mother at
      birth, and social class in childhood did not change these results. CONCLUSION:
      Our findings do not suggest that childhood vaccination against smallpox, even if
      given early in life, influences the development of atopy or allergic rhinitis.
      The association with asthma should be interpreted with caution and needs further
      study.

PMID- 12789222
TI  - Is the prevalence of adult asthma and allergic rhinitis still increasing? Results
      of an Italian study.
AB  - BACKGROUND: The prevalence of asthma and allergic rhinitis has increased
      worldwide during the 1970s and 1980s. OBJECTIVE: This study was aimed at
      evaluating whether the increasing trend in prevalence persisted during the 1990s
      in the young adult Italian population. METHODS: In 1998 to 2000 a screening
      questionnaire was sent by mail to a general population sample aged 20 to 44
      years; nonresponders were contacted again first by mail and then by phone,
      achieving a final response rate of 78.1% (6876 of 8800). Prevalence estimates,
      adjusted to correct for nonresponse bias, were compared with those recorded in
      Italy in 1991 to 1993 during the European Community Respiratory Health Survey,
      when response rate had been slightly higher (87.6%). Temporal variations in
      symptom prevalence were analyzed by a logistic regression model, controlling for
      sex, age, site of residence (urban vs suburban areas), season of response,
      response rate, and type of contact (mail vs phone). RESULTS: The prevalence of
      asthma attacks did not vary significantly from 1991 to 1993 (3.6%) to 1998 to
      2000 (3.2%) (P =.188). The prevalence of asthma-like symptoms (wheezing, chest
      tightness, shortness of breath) tended to decrease in the age classes of 32.5 to
      45 years, while increasing in the youngest age class (20 to 26 years). A clear
      cut increase from 15.4% to 18.3% was observed for the prevalence of allergic
      rhinitis (P <.001), whereas the proportion of people under antiasthmatic
      treatment increased in suburban areas but not in urban areas (interaction time
      site of residence, P <.001). CONCLUSION: Asthma prevalence has not increased
      during the last decade in Italy. The persistence of an increasing trend in
      allergic rhinitis prevalence deserves attention.

PMID- 12789223
TI  - Pregnancy outcome after gestational exposure to loratadine or antihistamines: a
      prospective controlled cohort study.
AB  - BACKGROUND: Loratadine is a second-generation histamine H(1)-receptor antagonist,
      used in the treatment of allergic conditions. No prospective controlled trials on
      loratadine in human pregnancy have been published to date. OBJECTIVE: To
      determine whether the use of loratadine or other antihistamines (OAH) is
      associated with an increased risk of major anomalies. METHODS: Callers who were
      counseled by the Israeli Teratogen Information Service in regard to loratadine or
      OAH exposure during pregnancy were prospectively collected and followed up.
      Pregnancy outcome was compared among three exposure groups: loratadine, OAH, and
      a control group of patients who were counseled for nonteratogenic exposure,
      nonteratogenic controls (NTC). The OAH included astemizole, chlorpheniramine,
      terfenadine, hydroxyzine, promethazine, and dimetindene. RESULTS: We followed up
      210 pregnancies exposed to loratadine (77.9% in the first trimester) and 267
      pregnancies exposed to OAH (64.6% in the first trimester) and compared pregnancy
      outcome with that of 929 NTC. The rate of congenital anomalies did not differ
      among the groups [loratadine: 4/175 (2.3%), OAH: 10/247 (4.0%), NTC: 25/844
      (3.0%), P =.553, relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to
      2.19, (loratadine vs NTC); RR, 0.56; 95% CI, 0.18 to 1.77, (loratadine vs OAH)].
      The rate did not differ between those exposed to antihistamines in the first
      trimester and the control patients [loratadine: 1/126 (0.8%), OAH: 7/146 (4.8%),
      NTC: 25/844 (3.0%), P =.152, RR, 0.27; 95% CI, 0.04 to 1.94, (loratadine vs NTC);
      RR, 0.17; 95% CI, 0.02 to 1.33, (loratadine vs OAH)]. CONCLUSIONS: This study on
      the use of loratadine in human pregnancy suggests that this agent does not
      represent a major teratogenic risk. The study was powered to find a 3-fold
      increase in the overall rate of major anomalies.

PMID- 12789224
TI  - Safety of cetirizine in infants 6 to 11 months of age: a randomized, double
      blind, placebo-controlled study.
AB  - BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic
      disorders in infants and children; however, there are few prospective,
      randomized, double-blind, controlled studies of these medications in young
      children, and to date, no such studies have been conducted in infants. OBJECTIVE:
      This prospective, randomized, parallel-group, double-blind, placebo-controlled
      study was designed to evaluate the safety of the H(1)-antihistamine cetirizine,
      particularly with regard to central nervous system and cardiac effects, in
      infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry
      criteria for age and had a history of treatment with an H(1)-antihistamine for an
      allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine
      orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily
      dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all
      cause or treatment-related adverse events were observed between the cetirizine-
      and placebo-treated groups. A trend was observed toward fewer adverse events and
      sleep-related disturbances in the cetirizine group compared with the placebo
      group. No prolongation in the linear corrected QT interval was observed in
      cetirizine-treated infants compared with either baseline values or with values in
      placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine
      in this short-term investigation, the first randomized, double-blind, placebo
      controlled study of any H(1)-antihistamine in infants. Additional prospective,
      randomized, double-blind, placebo-controlled, long-term studies of cetirizine and
      other H(1)-antihistamines are needed in this population.

PMID- 12789225
TI  - Presence of atopy in first-degree relatives as a predictor of a female proband's
      depression: results from the Northern Finland 1966 Birth Cohort.
AB  - BACKGROUND: Recent investigations suggest a common genetic rather than
      environmental cause to explain the association between IgE-mediated atopic
      allergies and depression. OBJECTIVE: Taking into account psychosocial confounding
      factors, we investigated separately and at the epidemiologic level the effects of
      maternal, paternal, and sibling atopy on the cumulative incidence of a child's
      depression. METHODS: We used an unselected, genetically homogenous, general
      population birth cohort of 12,058 live-born children in Finland. The 31-year
      prospective follow-up included questionnaire information on atopic disorders of
      the cohort members' parents and siblings. The probands' own atopic conditions
      were evaluated by means of skin prick tests, and information on lifetime
      depression diagnoses was gleaned from postal questionnaires and national hospital
      discharge registers. Potential confounders were mother's parity, father's social
      class, maternal smoking during pregnancy, proband's regular daily smoking, and
      proband's dwelling place. Total variable information was available from 4068
      cohort members. RESULTS: Among female probands, the presence of atopy in parents
      was the strongest predictor for lifetime depression (P <.001), and sibling atopy
      and parental atopy were the strongest predictors for hospital-treated depression
      (P =.018 and P =.036, respectively). After controlling for confounders, it was
      noticed that maternal atopy increased a female proband's risk of lifetime
      depression up to 1.9-fold (odds ratio, 1.9; 95% CI, 1.1-3.0). The corresponding
      risk increased over 4-fold if parental-maternal atopy was combined with proband's
      own atopy. CONCLUSIONS: Our findings suggest that maternal inheritance could be a
      significant causative factor in the association between atopy and depression of
      female probands.

PMID- 12789226
TI  - Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.
AB  - BACKGROUND: Immunotherapy involves the modulation of allergen-specific T-cell
      responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated
      patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing
      CD4+CD25+ regulatory T cells have emerged as potential mediators of immune
      tolerance in numerous murine models of immunopathology. OBJECTIVE: The aim of
      this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in
      the response to grass pollen immunotherapy. METHODS: PBMCs were isolated from
      patients after 1 year of grass pollen immunotherapy and from matched untreated
      atopic and healthy control subjects. After 6 days of in vitro stimulation with
      Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation
      and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for
      a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed
      for intracellular IL-10 by means of flow cytometry. RESULTS: Patients undergoing
      immunotherapy produced significantly more IL-10 than atopic control subjects
      (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients,
      30 +/- 5 pg/mL [n = 11]; P <.001), and the number of CD4+CD25+ cells identified
      after allergen stimulation was also greater in the immunotherapy group. The
      numbers of CD4+CD25+ T cells correlated positively with activation as measured by
      proliferation in both of the control groups but not in the immunotherapy group.
      Moreover, only T cells from patients undergoing immunotherapy were positive for
      intracellular IL-10, and these were almost exclusively CD4+CD25+ cells.
      CONCLUSION: Grass pollen immunotherapy results in a population of circulating T
      cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen
      restimulation.

PMID- 12789227
TI  - Monoclonal IgE antibodies against birch pollen allergens: novel tools for
      biological characterization and standardization of allergens.
AB  - BACKGROUND: IgE antibodies are key players in immediate hypersensitivity
      reactions. Allergen characterization and standardization is usually based on the
      sera of allergic patients, whereas monoclonal IgE antibodies specific for
      clinically relevant allergens are very rare. OBJECTIVE: The aim of this study was
      to establish IgE mAbs specific for birch pollen allergens, because these are
      important inhalant allergens. METHODS: IgE-producing hybridomas were identified
      by using the highly sensitive rat basophilic leukemia cell mediator release assay
      with enhanced allergen stimulation by additional cross-linking with birch pollen
      specific IgG antibodies. The obtained IgE mAbs were characterized by immunologic
      methods and by cDNA sequencing. RESULTS: Seven IgE mAbs specific for the birch
      pollen allergens Bet v 1 or Bet v 6 were obtained and were all biologically
      active in mast cell-based assays. Mediator release experiments with mAb
      combinations indicated that 2 different epitope regions were recognized on Bet v
      1, whereas the 2 Bet v 6-specific mAbs bound to the same epitope region. After
      sensitization of rat basophilic leukemia cells with IgE mAbs, different amounts
      of Bet v 1 or Bet v 6 were detected in commercial diagnostic allergen reagents,
      whereas sensitization with polyclonal IgE resulted in similar allergenic potency
      of all products. CONCLUSIONS: IgE mAbs represent promising novel tools for
      allergen characterization and component-resolved standardization of allergen
      extracts.

PMID- 12789228
TI  - Mite and mite allergen removal during machine washing of laundry.
AB  - BACKGROUND: Few studies have investigated live house dust mite and mite allergen
      removal from clothing and bedding by washing machines. No studies have
      investigated the transfer of mites from infested to uninfested clothing and
      bedding during washing. OBJECTIVE: The purpose of this study was to wash
      different types of clothing and bedding in residential washing machines to
      determine the live Dermatophagoides farinae mite and allergen removal and the
      mite transfer from mite-infested items to mite-free items. METHODS: Clothing and
      bedding items were machine washed in 6- and 8-lb loads in warm (36 degrees C-38
      degrees C) or cold (22 degrees C-27 degrees C) water with and without recommended
      concentrations of laundry detergent and sodium hypochlorite bleach. Live mites
      and allergen present in washed versus unwashed and washed mite-infested versus
      washed mite-free items were compared. RESULTS: Washing clothing and bedding in
      water alone, detergent, or detergent plus bleach removed 60% to 83% of the live
      mites. Washing removed more mites from some items than from others. When mite
      infested items were washed with identical sets of mite-free items, many live
      mites were transferred to the previously mite-free items. Overall, 84% of Der f 1
      was removed from items washed in water alone or in detergent and 98% from items
      washed in detergent plus bleach. CONCLUSIONS: Washing clothing and bedding in
      cold or warm water with detergent or detergent plus bleach removed most allergen
      and a significant (P <.05) portion of live mites. Repeated washing is required to
      further reduce mite levels. Live mites were transferred from mite-infested to
      mite-free items during washing.

PMID- 12789229
TI  - Fire ants represent an important risk for anaphylaxis among residents of an
      endemic region.
AB  - BACKGROUND: Imported fire ants (IFA) represent a potential anaphylactic risk to
      IFA-sensitized individuals. OBJECTIVE: We examined the prevalence of allergic
      sensitization to IFA, yellow jacket venom (YJV), and peanut in an adult
      population from an IFA-infested region, Augusta, Georgia. METHODS: Specific IgE
      to IFA, YJV, and peanut were determined by using the Pharmacia UniCAP assay in
      200 random blood donors from an Augusta blood bank. These results were compared
      with specific IgE to identical allergens in a random sample of blood donors from
      Oklahoma City, Oklahoma (OKC), a nonendemic region for IFA. RESULTS: Prevalence
      of IFA-specific IgE (17%) in the Augusta population was significantly higher than
      to YJV (10%, P =.04) or peanut (7.5%, P =.004). The majority of individuals who
      had significant IgE to IFA (> or =0.35 kIU/L) did not have IgE to YJV (24/34 =
      71%). YJV caused significantly more inhibition of IgE binding to a YJV solid
      phase than to an IFA solid phase when the 10 dual-positive sera were analyzed
      (58% vs 11%, P =.005). The prevalence of IFA-specific IgE in adults from Augusta
      was higher than in OKC (17% vs 2%, P =.0002). YJV-specific IgE was also more
      prevalent in Augusta compared with OKC (10% vs 6.0%, P =.04), whereas no
      difference was demonstrated for peanut-specific IgE (7.5% vs 6.5%, P =.6).
      CONCLUSIONS: Allergic specific IgE to IFA is 1.7 times more common in adults
      living in an endemic area than specific IgE for other allergens associated with
      potentially fatal anaphylaxis. This suggests that IFA may pose the greatest risk
      of anaphylaxis for adults residing in IFA-endemic regions.

PMID- 12789230
TI  - Matrix metalloproteinase inhibitor regulates inflammatory cell migration by
      reducing ICAM-1 and VCAM-1 expression in a murine model of toluene diisocyanate
      induced asthma.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has been reported to play a
      crucial role in the transmigration of neutrophils, lymphocytes, and eosinophils.
      Neutrophils, eosinophils, and lymphocytes migrate from the blood to the lungs in
      response to inflammatory mediators produced in the airways and are subsequently
      released into the circulation. This traffic is mediated by adhesion molecules.
      However, little is known about the migration of inflammatory cells through the
      endothelial and epithelial basement membranes in toluene diisocyanate (TDI)
      induced asthma. OBJECTIVES: An aim of this study was to evaluate the effect of
      MMP inhibitors on the expression of ICAM-1 and VCAM-1 in the migration of
      inflammatory cells in a murine model of TDI-induced asthma. METHODS: We used a
      murine model to investigate TDI-induced asthma to examine the possible
      involvement of ICAM-1 and VCAM-1 in the pathogenesis of that disease and the
      effect of MMP inhibitors on the expression of ICAM-1 and VCAM-1. RESULTS: In
      mice, the following typical pathophysiologic features develop in the lungs:
      increased numbers of inflammatory cells and increased expression of MMP-9, ICAM
      1, and VCAM-1 mRNA and protein. Administration of MMP inhibitors reduced the
      increased numbers of inflammatory cells and the increased expression of ICAM-1
      and VCAM-1 mRNA expression and protein. In addition, MMP inhibitors significantly
      abrogated the increased expression of IL-1beta, IL-4, and TNF-alpha mRNA in lung
      tissues and levels of IL-1beta, IL-4, and TNF-alpha in bronchoalveolar lavage
      fluids after TDI inhalation. CONCLUSIONS: These results suggest that MMP
      inhibitors regulate inflammatory cell migration by reducing ICAM-1 and VCAM-1
      expression and possibly also by suppressing IL-1beta, IL-4, and TNF-alpha
      expression.

PMID- 12789231
TI  - The RANTES promoter polymorphism: a genetic risk factor for near-fatal asthma in
      Chinese children.
AB  - BACKGROUND: RANTES promoter polymorphisms were found associated with asthma/atopy
      in some studies but not others, possibly reflecting the genetic heterogeneity
      among different ethnicities and different asthma severity. OBJECTIVE: The purpose
      of this investigation was to test the genetic association between the RANTES 
      28C/G and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children,
      with particular emphasis on those patients who had experienced life-threatening
      asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134
      children with mild-to-moderate asthma, 69 children with allergic disorders but no
      asthma, and 107 nonasthmatic nonatopic control children were genotyped through
      use of a PCR-based assay. RESULTS: No significant difference was demonstrated for
      frequency of the RANTES -28C/G polymorphism when the mild-to-moderate asthma,
      atopic/nonasthmatic, and normal control groups were compared. The RANTES -28G
      allele was present in a significantly higher proportion of the children with near
      fatal asthma compared with the nonasthmatic nonatopic controls (odds ratio, 2.93
      [1.41-6.06]; P =.006) and the children with mild-to-moderate asthma (odds ratio,
      3.52 [1.73-7.16]; P =.001). The frequency of -28G allele carriage correlated with
      asthma severity. The RANTES -28G allele was also associated with an increased
      blood eosinophil count and a higher degree of bronchial hyperresponsiveness. The
      RANTES -403G/A polymorphism did not influence asthma/atopy susceptibility, blood
      eosinophil count, or bronchial hyperresponsiveness. Interestingly, a higher
      frequency of -403A allele carriage was observed in the moderate asthma subgroup
      compared with the mild asthma analog. CONCLUSIONS: We conclude that the RANTES 
      28C/G polymorphism exacerbates asthma severity, representing a genetic risk
      factor for life-threatening asthma attacks in Chinese children. In addition, the
      linkage disequilibrium between these 2 polymorphisms is a potential confounder
      that must be considered in the design and interpretation of RANTES gene
      association studies.

PMID- 12789232
TI  - Airway remodeling-associated mediators in moderate to severe asthma: effect of
      steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression.
AB  - BACKGROUND: Important features of airway remodeling in asthma include the
      formation of subepithelial fibrosis and increased deposition of types I and III
      collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the
      formation of subepithelial fibrosis and are increased in patients with asthma,
      particularly in those with severe disease. OBJECTIVE: The purpose of this study
      was to investigate the effect of corticosteroids on the expression of these
      profibrotic cytokines and on extracellular matrix deposition. METHODS: We used
      immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and
      collagen types I and III in the airways of patients with mild asthma (n = 9),
      patients with moderate-to-severe asthma (n = 10), and control subjects without
      asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups.
      In addition, repeat biopsies were obtained in the patients with moderate-to
      severe asthma after a 2-week course of oral corticosteroids. RESULTS: TGF-beta
      expression was significantly higher in all groups with asthma, and it did not
      decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17
      were increased in patients with moderate-to-severe asthma compared with patients
      with mild asthma and normal controls (P <.05). The expression of these cytokines
      decreased with oral corticosteroids in the moderate-to-severe group to levels
      that were comparable to those seen in the patients with mild asthma and in the
      normal controls (P <.005). Expression of types I and III collagens was higher in
      the patients with moderate-to-severe asthma than in the patients with mild asthma
      and the controls (P <.05; P <.001). Treatment with corticosteroids did not
      decrease the expression of types I and III collagens. CONCLUSIONS: These results
      confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types
      I and III collagens with severe disease and suggest that the failure of cortico
      steroids to decrease collagen deposition might be due to persistently elevated
      TGF-beta expression.

PMID- 12789233
TI  - Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human
      basophils.
AB  - BACKGROUND: Activation of mast cells and basophils through allergen stimulation
      releases chemical mediators and synthesizes cytokines. Among these cytokines, IL
      4, IL-13, and IL-5 have major roles in allergic inflammation. OBJECTIVE: We
      sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol,
      myricetin, quercetin, and rutin) for the inhibition of cytokine expression and
      synthesis by human basophils. METHODS: The inhibitory effect of flavonoids on
      cytokine expression by stimulated KU812 cells, a human basophilic cell line, and
      freshly purified peripheral blood basophils was measured by means of
      semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on
      transcriptional activation of the nuclear factor of activated T cells were
      assessed by means of electrophoretic mobility shift assays. RESULTS: Fisetin
      suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187
      stimulated KU812 cells and basophils in response to cross-linkage of the IgE
      receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory
      concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively)
      but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited
      IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50)
      = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated
      basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids
      examined, kaempferol and quercetin showed substantial inhibitory activities in
      cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear
      localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812
      cells. CONCLUSION: These results provide evidence of a novel activity of the
      flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4,
      IL-13, and IL-5) by basophils.

PMID- 12789234
TI  - TH2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor
      production by cultured human airway smooth muscle cells is attenuated by IFN
      gamma and corticosteroids.
AB  - BACKGROUND: T(H)2 and T(H)1 cytokines have opposite effects on many aspects of
      the inflammatory response. METHODS: This study was designed to determine if
      cytokines possibly present in asthma can modulate airway smooth muscle cell
      (ASMC) production of vascular endothelial growth factor (VEGF) and thus
      contribute to altered airway vascularity. ASMC were incubated for 24 hours with
      various concentrations of T(H)2 cytokines (IL-4, IL-5, IL-10, and IL-13);
      transforming growth factor (TGF)-beta1, TGF-beta2, or TGF-beta3; and IL-1beta or
      TNF-alpha with or without IFN-gamma. Budesonide and exogenous prostaglandin
      (PG)E(2) were also evaluated. Postculture media were assayed for VEGF and PGE(2)
      by ELISA. RESULTS: IL-4, IL-5, and IL-13 alone but not IL-10 enhanced VEGF
      production by ASMC in a concentration-dependent manner. IFN-gamma alone inhibited
      spontaneous VEGF release by ASMC and concentration-dependently attenuated IL-4
      augmented, IL-5-augmented, or IL-13-augmented production of VEGF (P <.01). All
      three TGF-beta isoforms augmented VEGF production, which was reduced by IFN-gamma
      (P <.005). IL-1beta also increased VEGF production, but this was not affected by
      IFN-gamma (P >.05). TNF-alpha alone had little effect on VEGF release by ASMC.
      Production of VEGF stimulated by all cytokines was inhibited by budesonide.
      Exogenous PGE(2) increased VEGF release, but cytokine modulation of PGE(2)
      release did not always correlate with VEGF release. CONCLUSIONS: T(H)2 cytokines
      and TGF-beta stimulate ASMC release of VEGF. This can be inhibited by IFN-gamma
      and glucocorticoids.

PMID- 12789235
TI  - Segmental allergen challenge in patients with atopic asthma leads to increased IL
      9 expression in bronchoalveolar lavage fluid lymphocytes.
AB  - BACKGROUND: IL-9 is a T(H)2 cell-derived cytokine that might be involved in the
      pathophysiology of allergic diseases. Little is known about its expression and
      release during the allergic response in the human lung. OBJECTIVE: The expression
      of IL-9 was measured in 10 atopic subjects with mild asthma and 5 nonatopic
      healthy control subjects at baseline and 24 hours after segmental sham and
      allergen challenge. METHODS: IL-9 protein was measured in bronchoalveolar lavage
      (BAL) fluid by means of ELISA and detected within the BAL cells by means of
      immunocytochemistry. Furthermore, IL9 mRNA expression of BAL cells was detected
      by means of real-time PCR. RESULTS: Although only low or undetectable amounts of
      IL9 mRNA and IL-9 protein were present in nonatopic control subjects and atopic
      asthmatic patients at baseline, there was an increase after segmental allergen
      challenge in the atopic subjects. Lymphocytes were identified as major cellular
      sources of IL-9 production by means of immunocytochemistry. Furthermore, IL-9
      protein and IL9 mRNA expression correlated with eosinophil numbers in BAL fluid.
      CONCLUSIONS: These findings demonstrate that IL-9 is specifically upregulated
      after local allergen challenge in the lungs of atopic asthmatic patients.
      Lymphocytes are the major cellular source of IL-9. The increased expression and
      its correlation with eosinophil numbers suggest a potential role for IL-9 in the
      late phase of the allergic response.

PMID- 12789236
TI  - Native Art v 1 and recombinant Art v 1 are able to induce humoral and T cell
      mediated in vitro and in vivo responses in mugwort allergy.
AB  - BACKGROUND: Mugwort pollen is an important allergen source in hay fever and
      pollen-related food allergy. Little is known about the clinical relevance of the
      major mugwort allergen Art v 1 and its importance in allergy. OBJECTIVE: In this
      study we aimed to investigate the allergenicity of mugwort extract compared with
      the allergenicity of native (n)Art v 1 and recombinant (r)Art v 1, one major
      allergen of mugwort, in vivo and in vitro. METHODS: Thirty-two patients allergic
      to mugwort and 10 control subjects were investigated by means of skin prick and
      nasal provocation testing with different concentrations of mugwort extract, nArt
      v 1, and rArt v 1. nArt v 1 was purified from aqueous mugwort extract, and rArt v
      1 was cloned, expressed in Escherichia coli, and then purified. The in vitro
      allergenicity was measured by means of ImmunoCAP, ELISA, ELISA-inhibition
      experiments, and T-cell proliferation assays. RESULTS: nArt v 1 and rArt v 1 were
      able to elicit positive in vivo and in vitro reactions. The IgE-binding capacity,
      as determined by means of ELISA, was slightly higher for nArt v 1 than for rArt v
      1, and both allergens were able to induce T-cell proliferation in sensitized
      patients. However, rArt v 1 elicited a reduced response in skin and nasal
      provocation tests compared with nArt v 1. Compared with mugwort extract, both
      nArt v 1 and rArt v 1 showed lower sensitivity in patients with mugwort allergy
      in vivo. CONCLUSIONS: Art v 1, either in its native or recombinant form, is able
      to induce allergic reactions in patients with mugwort allergy. rArt v 1 induced
      comparable humoral and cell-mediated responses in vitro but showed reduced in
      vivo allergenicity compared with biochemically purified nArt v 1.

PMID- 12789237
TI  - Differential regulation of eotaxin expression by IFN-gamma in airway epithelial
      cells.
AB  - BACKGROUND: Eotaxin is a chemokine that binds with high affinity and specificity
      to the chemokine receptor CCR3 and plays an important role in the pathogenesis of
      allergic disease. OBJECTIVE: We studied the regulation of eotaxin expression by
      the T(H)1 cytokine IFN-gamma and analyzed its molecular mechanisms. METHODS:
      Levels of eotaxin mRNA and protein expression in the airway epithelial cell line
      BEAS-2B were determined with RT-PCR and ELISA. Mechanisms of transcriptional
      regulation were assessed by means of electrophoretic mobility shift assays and
      luciferase assay with eotaxin promoter-luciferase reporter plasmids. RESULTS:
      Although IFN-gamma did not directly induce the expression of eotaxin protein, it
      increased the induction by TNF-alpha when these cytokines were added
      simultaneously. In contrast, preincubation of cells with IFN-gamma for 24 hours
      profoundly inhibited the production induced by TNF-alpha. IFN-gamma did not
      influence the TNF-alpha-induced binding of nuclear factor kappaB to a DNA probe
      derived from the eotaxin promoter. IFN-gamma did not increase the ability of TNF
      alpha to activate the eotaxin promoter. Studies of eotaxin mRNA levels indicate
      that IFN-gamma combined with TNF-alpha increased the expression of eotaxin mRNA.
      When cells were preincubated with IFN-gamma, there was no inhibition of the
      appearance of eotaxin mRNA. CONCLUSION: These studies demonstrate that IFN-gamma
      enhances eotaxin expression when added in combination with TNF-alpha and
      profoundly inhibits eotaxin expression after preincubation. In both cases the
      available data indicate that the effect is mediated by a posttranscriptional
      mechanism.

PMID- 12789238
TI  - Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9:
      association with asthma severity, neutrophilic inflammation, and wound repair.
AB  - BACKGROUND: Asthma likely involves an active injury and repair process, including
      components such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although
      MMP-9 is increased in lavage fluid and sputum in patients with asthma,
      controversy exists as to the role of tissue MMP-9. OBJECTIVE: The purpose of this
      study was to determine whether increases in submucosal cellular MMP-9, matrix MMP
      9 (subepithelial basement membrane [SBM]), or both would be associated with
      severe asthma, neutrophilic inflammation, and wound repair. METHODS:
      Immunohistochemical staining and analyses of MMP-9, inflammatory cells,
      transforming growth factor beta, and collagen I were performed in endobronchial
      biopsy specimens, bronchoalveolar lavage fluid, or both from 38 patients with
      severe asthma and compared with results in 10 patients with mild asthma, 8
      patients with moderate asthma, and 10 healthy control subjects. RESULTS: A
      significantly greater proportion of patients with severe asthma demonstrated MMP
      9 staining of the SBM than control subjects (P =.02). Bronchoalveolar lavage MMP
      9 levels were also increased in patients with severe asthma (P =.0004). The
      numbers of submucosal neutrophils and macrophages, but not eosinophils, were
      significantly higher in asthmatic individuals with MMP-9 staining of the SBM (P
      =.004 and P =.01, respectively). However, the presence of SBM MMP-9 was
      associated with a high correlation between lavage and tissue eosinophils (r =
      0.58, P =.009). Although the SBM thickness did not differ between groups, higher
      numbers of transforming growth factor beta-positive cells were seen in subjects
      with SBM MMP-9 staining. Pulmonary function was significantly lower in those
      asthmatic subjects with SBM staining. CONCLUSIONS: These results suggest that
      localized tissue MMP-9 might play an important role in wound repair and cell
      trafficking.

PMID- 12789239
TI  - TH1-biased immunity induced by exposure to Antarctic winter.
AB  - BACKGROUND: Certain immune functions are known to be impaired in human beings
      exposed to Antarctic winter; in particular, decreased amounts of serum
      proinflammatory cytokines, such as TNF-alpha and IL-1, were noted. It is not
      known, however, whether this exposure has any effect on T-cell-mediated acquired
      immune functions. OBJECTIVES: This study aims to investigate whether exposure to
      Antarctic winter has any effect on T cell-dependent immune functions. METHODS: We
      assessed changes in various immunologic indicators, including serum levels of
      various cytokines, peripheral blood Valpha24Vbeta11 natural killer T cell
      numbers, and T(H)1/T(H)2 ratios of 40 Japanese personnel exposed to an Antarctic
      winter. Also, a 2-month inland traverse was executed during the isolation, and
      the effect on the above indicators was assessed. RESULTS: All subjects were
      healthy during the Antarctic isolation. The levels of serum TNF-alpha, IL-1Ra, IL
      6, and IL-1beta were dramatically reduced and remained at low levels throughout
      the isolation. The decrease in the levels of TNF-alpha and IL-1Ra was more
      pronounced during the inland traverse than during the rest of the isolation. The
      percentage of Valpha24Vbeta11 natural killer T cells was significantly increased
      at the midpoint of the isolation. Most interestingly, T(H)1/T(H)2 ratio was
      increased significantly, and this T(H)1 bias was most prominent at the late point
      of the isolation. CONCLUSIONS: Exposure to an Antarctic winter appeared to induce
      T(H)1-skewed immunity in human beings.

PMID- 12789240
TI  - Inhibition of the IL-4/IL-13 receptor system prevents allergic sensitization
      without affecting established allergy in a mouse model for allergic asthma.
AB  - BACKGROUND: IL-4 and IL-13 are considered as key regulators for the development
      of atopic disease. OBJECTIVE: This study addresses the therapeutic potential of
      an IL-4/IL-13 inhibitor on the basis of a mutated IL-4 variant (Q116D, Y119D)
      during allergic sensitization and in established disease in a murine asthma model
      with persistent airway pathologic condition. METHODS: BALB/c mice were sensitized
      with ovalbumin intranasally. Mice were treated with the IL-4/IL-13 inhibitor
      during the sensitization phase or alternatively after ovalbumin allergy was
      established. Specific antibodies were measured, and histologic lung sections were
      examined for goblet cell metaplasia. In addition, bronchoalveolar lavages were
      performed and checked for airway eosinophilia, IL-5 levels, and the number of IL
      4 secreting CD4(+) T cells. Furthermore, airway responsiveness to inhaled
      methacholine was assessed. RESULTS: The inhibition of the IL-4/IL-13 system
      during allergic sensitization resulted in a dose-dependent reduction of ovalbumin
      specific IgEs and inhibition of airway eosinophilia together with decreased IL-5
      levels and decreased numbers of IL-4 secreting CD4(+) T cells. Moreover, goblet
      cell metaplasia and airway responsiveness to methacholine could be reduced
      significantly by the IL-4/IL-13 inhibitor. However, the inhibition of the IL-4/IL
      13 system at various time points after allergy was established showed only little
      effect on all measured allergic parameters. CONCLUSION: Although the inhibition
      of the IL-4/IL-13 system can efficiently prevent the development of the allergic
      phenotype, these cytokines seem to play a minor role in established allergy. This
      is relevant for estimating the therapeutic effects of IL-4/IL-13 inhibitors in
      patients with allergic asthma.

PMID- 12789241
TI  - Trichosporon pullulans infection in 2 patients with chronic granulomatous
      disease: an emerging pathogen and review of the literature.
AB  - BACKGROUND: Chronic granulomatous disease is a genetically determined primary
      immunodeficiency disease in which phagocytic cells are unable to kill certain
      bacteria and fungi after ingestion. Manifestations include recurrent pyogenic
      infections caused by catalase-positive microbes. Trichosporon species are
      emerging as opportunistic agents that cause systemic disease in immunocompromised
      patients. Typically disease has been described in association with T beigelii in
      patients with secondary immunodeficiency, such as underlying malignancy.
      OBJECTIVE: The objective was to report the first 2 cases of T pullulans infection
      in 2 male children with chronic granulomatous disease. METHODS: The records of
      the 2 patients were reviewed. In addition, all cases of T pullulans infection
      reported in the English language literature are presented. RESULTS: This report
      brings to 7 the total number of cases of T pullulans reported and the first in
      patients with chronic granulomatous disease, one with invasive pneumonia and the
      other with an infected paronychium and localized cellulitis. In the 5 additional
      cases malignancy was the principal risk factor. CONCLUSION: T pullulans has
      rarely been reported as a fungal pathogen. The most prominent risk factor for the
      development of trichosporonosis is immunocompromise, most notably with
      neutropenia. Abnormally functioning neutrophils, such as with chronic
      granulomatous disease, may also predispose individuals to this opportunistic
      pathogen.

PMID- 12789242
TI  - Helper CD4+ T cells for IgE response to a dietary antigen develop in the liver.
AB  - BACKGROUND: Although T-cell responses to food antigens are normally inhibited
      either by deletion, active suppression, or both of antigen-specific T cells, T
      helper cells for IgE response to a food antigen still develop by unknown
      mechanisms in a genetically susceptible host. OBJECTIVE: We determined the site
      at which those IgE helper T cells develop. METHODS: We administered ovalbumin
      (OVA) orally to DO11.10 mice and studied CD4+ T cells in Peyer's patches, the
      spleen, and the liver. Helper activity for IgE response was assessed by
      adoptively transferring those CD4+ T cells to naive BALB/c mice, followed by
      systemic immunization with OVA. RESULTS: OVA-specific CD4+ T cells were deleted
      by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA
      specific CD4+ T cells that survived apoptosis in the liver expressed Fas ligand
      and secreted IL-4, IL-10, and transforming growth factor beta(1). CD4+ T cells
      producing IFN-gamma were deleted in the liver by repeated feeding of OVA. On
      transfer of CD4+ T cells to naive mice and systemic immunization with OVA, a
      marked increase in OVA-specific IgE response developed only in the mice that
      received hepatic CD4+ T cells from OVA-fed mice, the effect of which was not
      observed in the recipients of hepatic CD4+ T cells deficient in IL-4. In
      addition, significant suppression of delayed-type hypersensitivity and
      IgG(1)/IgG(2a) responses to OVA was observed in the recipients of hepatic CD4+ T
      cells, and this suppression required Fas/Fas ligand interaction. CONCLUSION:
      Together, these results suggested that a food antigen might negatively select
      helper T cells for IgE response to the antigen by preferential deletion of T(H)1
      cells in the liver.

PMID- 12789243
TI  - Transglutaminase-mediated cross-linking of a peptic fraction of omega-5 gliadin
      enhances IgE reactivity in wheat-dependent, exercise-induced anaphylaxis.
AB  - BACKGROUND: Patients with wheat-dependent, exercise-induced anaphylaxis (WDEIA)
      experience recurrent anaphylactic reactions when exercising after ingestion of
      wheat products. We have identified omega-5 gliadin (Tri a 19) as a major allergen
      in WDEIA, but the role of exercise in eliciting the symptoms remains obscure.
      OBJECTIVE: The aim was to examine whether tissue transglutaminase (tTG)-mediated
      cross-linking could be involved in modulating the IgE-binding ability and in vivo
      reactivity of digested omega-5 gliadin peptides in WDEIA. METHODS: Purified omega
      5 gliadin was digested with pepsin or with pepsin and trypsin and treated with
      tTG. The binding of IgE antibodies in pooled sera from 10 patients with WDEIA was
      studied by means of immunoblotting before and after tTG treatment of the digested
      peptides. The peptides derived from pepsin digestion were separated by means of
      gel-filtration chromatography, and IgE reactivity of 4 different peptide
      fractions was studied by immunoblotting before and after tTG treatment. The
      fraction showing the greatest degree of cross-linking by tTG was further studied
      by means of IgE ELISA, ELISA inhibition, and skin prick testing. RESULTS: The IgE
      binding ability of omega-5 gliadin was retained after pepsin and pepsin-trypsin
      digestion. tTG treatment of the whole peptic digest formed large peptide
      complexes, with molecular weights ranging from 40 to greater than 200 kd. These
      cross-linked aggregates bound IgE antibodies in immunoblotting more intensely
      than untreated, pepsin-digested, or pepsin-trypsin-digested omega-5 gliadin. A
      gel-filtration fraction of the whole peptic digest corresponding to the highest
      peak of the chromatogram and showing the greatest degree of tTG-mediated cross
      linking showed an increase in serum IgE reactivity in ELISA after tTG treatment,
      as well as a shift of reactivity to cross-linked complexes. In the 20 patients
      with WDEIA, the mean skin prick test wheal elicited by this tTG-treated peptic
      fraction was 77% larger (P <.001) than that elicited by the untreated peptic
      fraction and 56% larger (P <.01) than that elicited by intact omega-5 gliadin.
      CONCLUSIONS: Omega-5 gliadin-derived peptides are cross-linked by tTG, which
      causes a marked increase in IgE binding both in vitro and in vivo. Activation of
      tTG during exercise in the intestinal mucosa of patients with WDEIA could lead to
      the formation of large allergen complexes capable of eliciting anaphylactic
      reactions.

PMID- 12789244
TI  - Characterization of drug-specific T cells in lamotrigine hypersensitivity.
AB  - BACKGROUND: Lamotrigine is associated with hypersensitivity reactions, which are
      most commonly characterized by skin rash. An immune etiology has been postulated,
      though the nature of this is unclear. OBJECTIVES: The aim of this study was to
      characterize the role of T cells in lamotrigine hypersensitivity. METHODS: A
      lymphocyte transformation test was performed on 4 hypersensitive patients.
      Lymphocytes from 3 of 4 lamotrigine-hypersensitive patients proliferated when
      stimulated with lamotrigine. T-cell clones were generated from one patient to
      further characterize the nature of the T-cell involvement. Cells were
      characterized in terms of their phenotype, functionality, and mechanisms of
      antigen presentation and cytotoxicity. RESULTS: Of the 44 drug-specific T-cell
      clones generated, most were CD4(+) with occasional CD8(+) cells. All clones
      expressed the alphabeta T-cell receptor; several Vbeta 5.1(+) or 9(+) T-cell
      clones were generated. All clones also expressed the skin-homing receptor
      cutaneous lymphocyte antigen. Lamotrigine-stimulated T cells were cytotoxic and
      secreted perforin, IFN-gamma, IL-5, and macrophage inflammatory protein 1alpha,
      macrophage inflammatory protein 1beta, RANTES, and I-309. Lamotrigine was present
      on HLA-DR and HLA-DQ by antigen-presenting cells in the absence of drug
      metabolism and processing. The T-cell receptor of certain clones could
      accommodate analogs of lamotrigine, but no cross-reactivity was seen with other
      anticonvulsants. CONCLUSIONS: Our data provide evidence that T cells are involved
      in the pathogenesis of some lamotrigine-hypersensitivity reactions. The
      identification of drug-specific cells that express cutaneous lymphocyte antigen
      and type 1 cytokines after T-cell receptor activation is consistent with the
      clinical symptoms. Furthermore, identification of large numbers of Vbeta 5.1(+) T
      cells suggests that polymorphisms within T-cell receptor genes might act as
      determinants of susceptibility.

PMID- 12789245
TI  - Selective celecoxib-associated anaphylactoid reaction.

PMID- 12789246
TI  - Atopy and allergic respiratory diseases in multitransfused patients: a new
      insight into the increase in the prevalence of atopy.

PMID- 12789247
TI  - Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful
      sublingual allergen immunotherapy.

PMID- 12789248
TI  - Oral tacrolimus for severe recalcitrant atopic eczema.

PMID- 12789249
TI  - Anaphylaxis caused by skin prick testing with aeroallergens: Case report and
      evaluation of the risk in Italian allergy services.

PMID- 12789251
TI  - Study design is a major determinant of whether equivalence or superiority is
      demonstrated.

PMID- 12789252
TI  - Clinical laboratory assessment of IgE.

PMID- 12789254
TI  - Rapid effect of inhaled fluticasone on airway responsiveness to AMP: research
      implications.

PMID- 12789257
TI  - Airway remodeling in asthma.

PMID- 12789259
TI  - pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1
      multimolecular complexes mediate the transcription of estrogen receptor-alpha in
      breast cancer.
AB  - The estrogen receptor-alpha (ER) plays a crucial role in normal breast
      development and is also linked to development and progression of mammary
      carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an
      area of active investigation with potential clinical significance. However, the
      molecular mechanisms that regulate the ER-alpha gene expression are not fully
      understood. Here we show a new molecular mechanism of ER-alpha gene inactivation
      mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo
      occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and
      pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between
      pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha
      transcription in a physiological setting. These findings suggest that pRb2/p130
      multimolecular complexes can be key elements in the regulation of ER-alpha gene
      expression and may be viewed as promising targets for the development of novel
      therapeutic strategies in the treatment of breast cancer, especially for those
      tumors that are ER negative.

PMID- 12789260
TI  - Triggering of p73-dependent apoptosis in osteosarcoma is under the control of
      E2Fs-pRb2/p130 complexes.
AB  - Mechanisms underlying multidrug resistance (MDR), one of the major causes of
      cancer treatment failure, are still poorly understood. We selected the
      osteosarcoma MDR HosDXR150 cell line by culturing Hos cells in the presence of
      increasing doxorubicin doses and showed that it is crossresistant to vinblastine.
      Similarly to the Hos parental cell line, HosDXR150 cells present mutated p53,
      functionally inactivated pRb/p105 and wild-type pRb2/p130. Owing to p53 mutation,
      MDR-1 gene, codifying for P-glycoprotein, is upregulated. Evasion of apoptosis in
      HosDXR150 cells is only partially explained by drug extrusion because of P
      glycoprotein overexpression. Analysis of gene expression level profiles showed
      that parental cell line undergoes apoptosis through an E2F1/p73-dependent pathway
      while its resistant variant evades it. This result can be explained by the
      presence of distinct E2Fs-pRb2/p130 complexes on the p73 promoter. Namely, in Hos
      p73 transcription is activated by E2F1-Rb2/p130-p300 complexes, while in
      HosDXR150 it is kept repressed by E2F4-Rb2/p130-HDAC1 complexes.

PMID- 12789261
TI  - Oxidative damage to cellular and isolated DNA by homocysteine: implications for
      carcinogenesis.
AB  - Homocysteine is considered to be an important risk factor for cancer as well as
      cardiovascular diseases. To clarify whether homocysteine has potential
      carcinogenicity, we investigated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxodG), which is known to be correlated with the incidence of cancer, induced
      by homocysteine in human cultured cell lines. Homocysteine increased the amount
      of 8-oxodG in human leukemia cell line HL-60, whereas the amount of 8-oxodG in
      its hydrogen peroxide (H(2)O(2))-resistant clone HP100 was not increased. We
      investigated the mechanism for oxidative DNA damage by homocysteine using (32)P
      labeled DNA fragments obtained from human tumor suppressor genes and a proto
      oncogene. There were two mechanisms by which homocysteine caused DNA damage in
      the presence of Cu(II). A low concentration of homocysteine (20 microM)
      frequently induced piperidine-labile sites at thymine residues, whereas a high
      concentration of homocysteine (100 microM) resulted in damage principally to
      guanine residues. Catalase inhibited DNA damage by 20 microM homocysteine,
      indicating the participation of H(2)O(2), but was ineffective in preventing DNA
      damage by 100 microM homocysteine. Experiments using a singlet oxygen probe
      showed that 100 microM homocysteine enhanced chemiluminescence intensity in
      deuterium oxide more than that in H(2)O. These results indicated that the metal
      dependent DNA damage through H(2)O(2) is likely to be a more relevant mechanism
      for homocysteine carcinogenicity.

PMID- 12789262
TI  - Procaspase 3 expression in ovarian carcinoma cells increases survivin
      transcription which can be countered with a dominant-negative mutant, survivin
      T34A; a combination gene therapy strategy.
AB  - Increased survivin expression is a negative prognostic marker in many tumours,
      including ovarian cancer. We show here that ovarian carcinoma cells upregulate
      survivin transcription in response to increased expression of the proapoptotic
      protein procaspase 3. We have utilized this observation in a combination gene
      therapy strategy using adenoviral constructs expressing the dominant-negative
      mutant survivin T34A (Ad Survivin T34A) and procaspase 3 (Ad Caspase 3) in
      ovarian carcinoma cell lines. Transfection of ovarian carcinoma cells with Ad
      Survivin T34A induces apoptosis via a caspase 9-mediated pathway that is not
      affected by cell cycle block prior to G2/M. Ad Survivin T34A-induced apoptosis
      can be significantly enhanced by cotransfection with Ad Caspase 3, and the
      combination of Ad Survivin T34A and Ad Caspase 3 leads to a significant increase
      in survival in a murine intraperitoneal ovarian carcinoma model with some long
      term survivors. This suggests that inhibiting endogenous survivin activity while
      also delivering high levels of procaspase 3 allow proteolytic cleavage and
      activation of the terminal caspase cascade leading to tumour cell death.

PMID- 12789264
TI  - A novel mechanism of tumor suppression by destabilizing AU-rich growth factor
      mRNA.
AB  - The occurrence of pathologically stable mRNAs of proto-oncogenes, growth factors
      and cyclins has been proposed to contribute to experimental and human
      oncogenesis. In normal resting cells, mRNAs containing an AU-rich element (ARE)
      in their 3' untranslated region are subjected to rapid degradation.
      Tristetraprolin (TTP) is an RNA-binding zinc-finger protein that promotes decay
      of ARE-containing mRNAs. Here we report that TTP acts as a potent tumor
      suppressor in a v-H-ras-dependent mast cell tumor model, where tumors express
      abnormally stable interleukin-3 (IL-3) mRNA as part of an oncogenic autocrine
      loop. Premalignant v-H-ras cells were transfected with TTP and injected into
      syngeneic mice. TTP expression delayed tumor progression by 4 weeks, and late
      appearing tumors escaped suppression by loss of TTP. When transfected into a
      fully established tumor line, TTP reduced cloning efficiency in vitro and growth
      of the inoculated cells in vivo. Transgenic TTP interfered with the autocrine
      loop by enhancing the degradation of IL-3 mRNA with concomitant reduction of IL-3
      secretion. Our data establish the ARE as an antioncogenic target in a model
      situation, underline the importance of mRNA stabilization in oncogenesis and show
      for the first time that tumor suppression can be achieved by interfering with
      mRNA turnover.

PMID- 12789263
TI  - Transcripts in pretreatment biopsies from a three-arm randomized trial in
      metastatic non-small-cell lung cancer.
AB  - Non-small-cell lung cancer patients with locally advanced or metastatic disease
      at the time of diagnosis show marginal response to chemotherapy in terms of tumor
      shrinkage, time to progression and median survival. The identification and
      implementation of predictive genetic markers of response-specific cytotoxic drugs
      is a priority of current research and future trials. In this study, we have used
      quantitative PCR to analyse expression of beta-tubulin III, stathmin, RRM1, COX-2
      and GSTP1 in mRNA isolated from paraffin-embedded tumor biopsies of 75 nonsmall
      cell lung cancer patients treated as part of a large randomized trial. In total,
      22 patients were treated with gemcitabine/cisplatin, 25 with
      vinorelbine/cisplatin and 28 with paclitaxel/carboplatin. There were no
      differences in clinical characteristics and transcript levels in the pretreatment
      biopsies according to treatment arm. Patients with low beta-tubulin III levels
      had better response in the paclitaxel/carboplatin arm (P=0.05), and those with
      low RRM1 levels showed a tendency to better response in the gemcitabine/cisplatin
      arm. Time to progression was influenced by beta-tubulin III (P=0.03) and stathmin
      (P=0.05) levels in the vinorelbine/cisplatin arm, and there was a tendency toward
      correlation between beta-tubulin III levels and time to progression in the
      paclitaxel/carboplatin arm. RRM1 levels influenced time to progression (P=0.05)
      and even more so, survival (P=0.0028) in the gemcitabine/cisplatin arm. The
      predictive value of beta-tubulin III, stathmin and RRM1 should be tested in
      prospective customized chemotherapy trials, the results of which will help tailor
      chemotherapy to improve patient survival.

PMID- 12789265
TI  - Kos1, a nonreceptor tyrosine kinase that suppresses Ras signaling.
AB  - Kinase of embryonic stem cells (Kos1), a nonreceptor protein tyrosine kinase
      (NRPTK), was identified and cloned from differentiating murine embryonic stem
      cells. Kos1 is localized on mouse chromosome 11 that corresponds to human
      chromosome 17p13.1 and is homologous to Tnk1, Ack1 and Ack2, making it a new
      member of the Ack family of NRPTKs. Kos1 is a ubiquitously expressed 47-kDa
      protein with autotyrosine kinase activity that is developmentally regulated
      during embryogenesis. Kos1 is also upregulated following IL3 withdrawal from
      factor-dependent murine NSF/N1.H7 cells that undergo apoptosis, suggesting a role
      in growth inhibition. Stable overexpression of Kos1 inhibits growth of NIH 3T3
      cells, while the kinase-dead Kos1(CN) promotes cell growth in both liquid culture
      and soft agar. In addition, forced expression of Kos1 inhibits Ras activity in an
      indirect mechanism that results in the downregulation of the Ras-Raf1-MAPK growth
      pathway. Furthermore, overexpression of Kos1 in NCI-H82 lung cancer cells that
      express oncogenic Ha-Ras(G12V) inhibits cell growth under reduced serum (0.5%)
      conditions in close association with the upregulation of the Ras inhibitor,
      Rap1A. Collectively, these data support a negative regulatory role for Kos1 in
      regulating the Ras-Raf1-MAPK growth pathway by a mechanism that requires its
      autotyrosine kinase activity.

PMID- 12789266
TI  - Transformation-selective apoptotic program triggered by farnesyltransferase
      inhibitors requires Bin1.
AB  - Neoplastic transformation sensitizes many cells to apoptosis. This phenomenon may
      underlie the therapeutic benefit of many anticancer drugs, but its molecular
      basis is poorly understood. We have used a selective and potent
      farnesyltransferase inhibitor (FTI) to probe a mechanism of apoptosis that is
      peculiarly linked to neoplastic transformation. While nontoxic to untransformed
      mouse cells, FTI triggers a massive RhoB-dependent, p53-independent apoptosis in
      mouse cells that are neoplastically transformed. Here we offer evidence that the
      BAR adapter-encoding tumor suppressor gene Bin1 is required for this
      transformation-selective death program. Targeted deletion of Bin1 in primary
      mouse embyro fibroblasts (MEFs) transformed by E1A+Ras did not affect FTI-induced
      reversion, actin fiber formation, or growth inhibition, but it abolished FTI
      induced apoptosis. The previously defined requirement for RhoB in these effects
      suggests that Bin1 adapter proteins act downstream or in parallel to RhoB in cell
      death signaling. The death defect in Bin1 null cells was significant insofar as
      it abolished FTI efficacy in tumor xenograft assays. p53 deletion did not
      phenocopy the effects of Bin1 deletion. However, MEFs transformed by SV40 large T
      antigen+Ras were also resistant to apoptosis by FTI, consistent with other
      evidence that large T inhibits Bin1-dependent cell death by a p53-independent
      mechanism. Taken together, the results define a function for Bin1 in apoptosis
      that is conditional on transformation stress. This study advances understanding
      of the functions of BAR adapter proteins, which are poorly understood, by
      revealing genetic interactions with an Rho small GTPase that functions in stress
      signaling. The frequent losses of Bin1 expression that occur in human breast and
      prostate cancers may promote tumor progression and limit susceptibility to FTI or
      other therapeutic agents that exploit the heightened sensitivity of neoplastic
      cells to apoptosis.

PMID- 12789267
TI  - v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL
      receptor-related protein 1.
AB  - We recently observed that the LDL receptor-related protein 1 (LRP-1) is tyrosine
      phosphorylated in v-Src-transformed cells. Using a GST-fusion protein containing
      the cytoplasmic domain of LRP-1, we show that LRP-1 is a direct substrate for v
      Src in vitro. To study LRP-1 phosphorylation in vivo, we constructed an LRP-1
      minireceptor composed of the beta chain linked at the amino-terminus to a Myc
      epitope (Myc-LRPbeta). When expressed together with v-Src, Myc-LRPbeta becomes
      phosphorylated on tyrosine. Of the four tyrosine residues present in the
      cytoplasmic domain of LRP-1, only Tyr 63 is phosphorylated by v-Src in vivo or in
      vitro. Using fibroblasts deficient in Src, Yes and Fyn, we were able to show that
      there are multiple kinases present in the cell that can phosphorylate LRP-1.
      Tyrosine-phosphorylated LRP-1 associates with Shc, a PTB and SH2 domain
      containing signaling protein that is involved in the activation of Ras. Binding
      of the purified Shc PTB domain to Tyr 63 containing peptides shows that the
      interaction between LRP-1 and Shc is direct. We found that DAB, a PTB domain
      containing signaling protein that is involved in signaling by LDL receptor
      related proteins in the nervous system, did not bind to full-length LRP-1. Our
      observations suggest that LRP-1 may be involved in normal and malignant signal
      transduction through a direct interaction with Shc adaptor proteins.

PMID- 12789268
TI  - Atypical expression of ErbB3 in myeloma cells: cross-talk between ErbB3 and the
      interferon-alpha signaling complex.
AB  - We have previously demonstrated that the responsiveness of multiple myeloma (MM)
      cells to interferon-alpha (IFN-alpha) stimulation is variable, with an atypical
      growth response displayed by some cells. Here we report the ability of IFN-alpha
      to induce tyrosine phosphorylation of a 180 kDa band in the KAS-6/1 MM cell line,
      which is growth responsive to IFN-alpha. Further characterization demonstrated
      that this band corresponds to ErbB3. To our knowledge, this is the first report
      of ErbB3 expression in a cell type of the hematopoietic lineage. Although ErbB
      receptors have been shown to crosscommunicate with various other receptors, our
      results show for the first time that the IFN-alpha receptor can crosscommunicate
      with ErbB3. To address the significance of these observations, we transfected
      ErbB3-negative DP-6 MM cells with ErbB3 and used siRNA to silence ErbB3 in the
      KAS-6/1 cell line. Although IFN-alpha transactivated ErbB3 in the DP-6
      transfectants, it did not confer growth responsiveness to IFN-alpha.
      Interestingly, silencing ErbB3 expression in the KAS-6/1 cells decreased the
      overall growth response to IFN-alpha and to interleukin-6. These results suggest
      that ErbB3 expression alone does not uniquely confer IFN-alpha growth
      responsiveness, but instead may amplify proliferation rates in MM cells that have
      acquired atypical expression of this receptor.

PMID- 12789269
TI  - Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by
      cdk2.
AB  - The signal transducing protein Stat3 activates gene transcription in cells in
      response to multiple cytokines. Constitutive activation of Stat3 has been
      observed in solid tumors including head and neck squamous cell carcinoma. Stat3
      activation in cancer has been associated with autocrine stimulatory loops and is
      believed to convey a growth advantage to cells. We now demonstrate ligand
      independent activation of Stat3 by high cell density in multiple cancer cell
      lines. Activation of Stat3 is associated with antiproliferative rather than
      proliferative conditions. Interference with cdk2 activity upregulates Stat3
      phosphorylation and Stat3-directed DNA-binding activity. Our data supports a
      model in which Stat3 activity is partially suppressed by cdk2 in growing cells
      and derepressed upon cell confluence.

PMID- 12789270
TI  - Neurotrophin-induced melanoma cell migration is mediated through the actin
      bundling protein fascin.
AB  - Expression of the p75 neurotrophin receptor (p75(NTR)) in primary melanomas is
      associated with deeply invasive lesions. In turn, there is expression of high
      levels of neurotrophins at the invasion front of normal tissue adjacent to brain
      metastases, thus implicating this growth factor-receptor system in melanoma
      tumorigenesis. The neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT
      3) are potent chemotactic agents for human melanoma cells which express
      p75(NTR)in vitro. Here we show that the actin-bundling protein fascin
      specifically interacts with p75(NTR) in an NGF-dependent manner by co
      immunoprecipitation and colocalization in melanoma cells that express the two
      proteins endogenously. In addition, expression of a fascin point mutant at the
      serine phosphorylation site (serine 39) regulating actin binding abrogates
      neurotrophin-induced migration. These results suggest a causal role for NGF
      mediated dephosphorylation of serine 39 on fascin in mediating actin binding and
      subsequent melanoma cell migration.

PMID- 12789271
TI  - Mutant p53 and aberrant cytosine methylation cooperate to silence gene
      expression.
AB  - p53 is an important transcriptional regulator that is frequently mutated in
      cancer. Gene-profiling experiments of breast cancer cells infected with wt p53
      revealed both MASPIN and desmocollin 3 (DSC3) to be p53-target genes, even though
      both genes are silenced in association with aberrant cytosine methylation of
      their promoters. Despite the transcriptional repression of these genes by
      aberrant DNA methylation, restoration of p53 resulted in the partial reactivation
      of both genes. This reactivation is a result of wt p53 binding to its consensus
      DNA-binding sites within the MASPIN and DSC3 promoters, stimulating histone
      acetylation, and enhancing chromatin accessibility of their promoters.
      Interestingly, wt p53 alone did not affect the methylation status of either
      promoter, suggesting that p53 itself can partially overcome the repressive
      barrier of DNA methylation. Pharmacologic inhibition of DNA methylation with 5
      aza-2'-deoxycytidine in combination with restoration of wt p53 status resulted in
      a synergistic reactivation of these genes to near-normal levels. These results
      suggest that cancer treatments that target both genetic and epigenetic facets of
      gene regulation may be a useful strategy towards the therapeutic transcriptional
      reprogramming of cancer cells.

PMID- 12789272
TI  - deltaNp63alpha functions as both a positive and a negative transcriptional
      regulator and blocks in vitro differentiation of murine keratinocytes.
AB  - deltaNp63 is overexpressed in squamous carcinomas where it is associated with
      proliferation and is believed to enhance cell growth by blocking p53-mediated
      transactivation. In normal epithelium, deltaNp63alpha protein expression is
      abundant in basal cells and decreases with differentiation. To explore the
      biological consequences of deltaNp63alpha overexpression in relation to squamous
      carcinogenesis, we evaluated its effect on normal squamous differentiation and
      p53 transactivation function in keratinocytes. Forced overexpression of
      deltaNp63alpha in primary murine keratinocytes in vitro inhibits morphological
      differentiation induced by elevated extracellular [Ca(2+)], abrogates Ca(2)(+)
      induced growth arrest, and blocks expression of maturation-specific proteins
      keratin 10 and filaggrin. This suggests that deltaNp63 overexpression in squamous
      carcinomas may serve to maintain the basal cell phenotype and promote cell
      survival. deltaNp63alpha blocks transactivation of p53 responsive reporter
      constructs mediated by endogenous or exogenous p53 at 17 h postinfection, as
      expected. However, at 41 h, when p53-mediated transactivation is diminished,
      deltaNp63alpha enhances transactivation of these reporter constructs by 2.2-12
      fold over control. Maximal deltaNp63alpha-induced transactivation requires intact
      p53 responsive elements, but is independent of cellular p53 status. This positive
      transcriptional function of deltaNp63alpha appears to be cell-type specific, as
      it is not observed in primary dermal fibroblasts or Saos-2 cells. These findings
      support deltaNp63alpha as a master regulator of keratinocyte differentiation, and
      suggest a novel function of this protein in the maintenance of epithelial
      homeostasis.

PMID- 12789273
TI  - Global transcriptional program of p53 target genes during the process of
      apoptosis and cell cycle progression.
AB  - The temporal gene expression profile during the entire process of apoptosis and
      cell cycle progression in response to p53 in human ovarian cancer cells was
      explored with cDNA microarrays representing 33 615 individual human genes. A
      total of 1501 genes (4.4%) were found to respond to p53 (approximately 80% of
      these were repressed by p53) using 2.5-fold change as a cutoff. It was
      anticipated that most of p53 responsive genes resulted from the secondary effect
      of p53 expression at late stage of apoptosis. To delineate potential p53 direct
      and indirect target genes during the process of apoptosis and cell cycle
      progression, microarray data were combined with global p53 DNA-binding site
      analysis. Here we showed that 361 out of 1501 p53 responsive genes contained p53
      consensus DNA-binding sequence(s) in their regulatory region, approximately 80%
      of which were repressed by p53. This is the first time that a large number of p53
      repressed genes have been identified to contain p53 consensus DNA-binding
      sequence(s) in their regulatory region. Hierarchical cluster analysis of these
      genes revealed distinct temporal expression patterns of transcriptional
      activation and repression by p53. More genes were activated at early time points,
      while more repressed genes were found after the onset of apoptosis. A small-scale
      quantitative chromatin immunoprecipitation analysis indicated that in vivo p53
      DNA interaction was detected in eight out of 10 genes, most of which were
      repressed by p53 at the early onset of apoptosis, suggesting that a portion of
      p53 target genes in the human genome could be negatively regulated by p53 via
      sequence-specific DNA binding. The approaches and genes described here should aid
      the understanding of global gene regulatory network of p53.

PMID- 12789274
TI  - MLL-mediated transcriptional gene regulation investigated by gene expression
      profiling.
AB  - The human mixed lineage leukemia (MLL) gene is involved in about 50 different
      chromosomal translocations, associated with the disease phenotype of acute
      leukemia. However, the normal function of MLL is less understood. Homozygous
      knockouts of murine Mll were embryonal lethal, while heterozygous disruption led
      to aberrant hox gene expression associated with skeletal malformations, growth
      retardation, and impaired hematopoiesis. To understand MLL functions on the
      molecular level, gene expression profiling experiments were performed with a pair
      of murine cell lines (MLL(+/+) and MLL(-/-)). Microarray hybridization
      experiments revealed 197 potential target genes that are differentially
      expressed, providing new and important clues about MLL functions.

PMID- 12789276
TI  - Development of melanocyte precursors from the vertebrate neural crest.
AB  - Pigment cells that differentiate in the vertebral skin arise from the neural
      crest (NC), a transitory structure formed at the dorsal borders of the neural
      plate and which gives rise to migratory cells of multiple fates. How NC cells
      become committed to the melanocytic lineage and what factors control the
      survival, proliferation and differentiation of melanocyte precursors remain
      largely unknown. These issues are of great importance for understanding the
      mechanisms of several pigment cell pathologies including melanomas. Recent in
      vivo and in vitro analyses of the fate of single NC cells have indicated that
      multipotent cells yield melanocyte precursors that become spatially and
      temporally segregated from other, non melanogenic, NC-derived cell types. The
      proper development of subsets of NC precursors is governed by environmental local
      cytokines acting in a paracrine manner. The conjunction of recent studies in
      mammals and birds reviewed here focuses on the action of endothelin 3 in
      controlling both the emergence and the maintenance of the NC-derived melanocyte
      phenotype.

PMID- 12789277
TI  - The importance of having your SOX on: role of SOX10 in the development of neural
      crest-derived melanocytes and glia.
AB  - SOX10 is a member of the high-mobility group-domain SOX family of transcription
      factors, which are ubiquitously found in the animal kingdom. Disruption of neural
      crest development in the Dominant megacolon (Dom) mice is associated with a Sox10
      mutation. Mutations in human Sox10 gene have also been linked with the occurrence
      of neurocristopathies in the Waardenburg-Shah syndrome type IV (WS-IV), for which
      the Sox10(Dom) mice serve as a murine model. The neural crest disorders in the
      Sox10(Dom) mice and WS-IV patients consist of hypopigmentation, cochlear
      neurosensory deafness, and enteric aganglionosis. Consistent with these
      observations, a critical role for SOX10 in the proper differentiation of neural
      crest-derived melanocytes and glia has been demonstrated. Emerging data also show
      an important role for SOX10 in promoting the survival of neural crest precursor
      cells prior to lineage commitment. Several genes whose regulation is dependent on
      SOX10 function have been identified in the peripheral nervous system and in
      melanocytes, helping to begin the identification of the multiple pathways that
      appear to be modulated by SOX10 activity. In this review, we will discuss the
      biological relevance of these target genes to neural crest development and the
      properties of Sox10 as a transcription factor.

PMID- 12789278
TI  - Microphthalamia-associated transcription factor: a critical regulator of pigment
      cell development and survival.
AB  - The microphthalamia-associated transcription factor (MITF) is an integral
      transcriptional regulator in melanocyte, the lineage from which melanoma cells
      originate. This basic-helix-loop-helix-leucine-zipper (bHLHzip) protein is
      critical for melanocyte cell-fate choice during commitment from pluripotent
      precursor cells in the neural crest. Its role in differentiation pathways has
      been highlighted by its potent transcriptional and lineage-specific regulation of
      the three major pigment enzymes: tyrosinase, Tyrp1, and Dct as well as other
      pigmentation factors. However, the cellular functions of MITF seem to be wider
      than differentiation and cell-fate pathways alone, since melanocytes and melanoma
      cells appear to require an expression of this factor. Here, we discuss the
      transcriptional networks in which MITF is thought to reside and describe
      signaling pathways in the cell which impinge on MITF. Accumulating evidence
      supports the notion that MITF is involved in survival pathways during normal
      development as well as during neoplastic growth of melanoma.

PMID- 12789279
TI  - Melanoma etiology: where are we?
AB  - Melanoma incidence rates are rising rapidly, particularly in older men. Older men
      are also more likely to have thick melanomas, which confer high mortality and
      morbidity. The reasons for the rate of increase are not known; increasing sun and
      UV exposure, however, is the major hypothesized explanation. In the past several
      years, two major susceptibility genes for melanoma, CDKN2A and CDK4, have been
      identified, but the two genes together account for a minority of familial
      melanoma. Other high-risk susceptibility genes are being sought actively. Genetic
      epidemiologic studies suggest that penetrance of each of the two identified genes
      is altered by other factors, either genetic or environmental. Epidemiologic
      studies have also identified other major host factors important in the
      development of melanoma. In European, North American, and Australian populations,
      the presence of clinically identified dysplastic nevi confers greatly increased
      risk of melanoma. A new measure of sun exposure, based on individual residential
      history, confers substantially increased risk of melanoma. Recent surveys of sun
      behavior in the US reveal extensive sunburning and use of tanning beds in
      adolescents and adults. Sun protective behaviors are not as prevalent as in
      Australia, where population rates of melanoma are stabilizing.

PMID- 12789280
TI  - Genetics of melanoma predisposition.
AB  - Predisposition to melanoma is genetically heterogeneous. Two high penetrance
      susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is
      ongoing to localize and identify others. With the advent of a catalogue of
      millions of potential DNA polymorphisms, attention is now also being focused on
      identification of genes that confer a more modest contribution to melanoma risk,
      such as those encoding proteins involved in pigmentation, DNA repair, cell growth
      and differentiation or detoxification of metabolites. One such pigmentation gene,
      MC1R, has not only been found to be a low penetrance melanoma gene but has also
      been shown to act as a genetic modifier of melanoma risk in individuals carrying
      CDKN2A mutations. Most recently, an environmental agent, ultraviolet radiation,
      has also been established as a modifier of melanoma risk in CDKN2A mutation
      carriers. Hence, melanoma is turning out to be an excellent paradigm for studying
      gene-gene and gene-environment interactions.

PMID- 12789281
TI  - Human melanocyte senescence and melanoma susceptibility genes.
AB  - The molecular mechanisms and biology of cellular senescence in human melanocytes
      are discussed, including similarities to and differences from senescence in
      fibroblasts and other cell lineages. Special reference is made to the fact that
      the known melanoma susceptibility genes in the human, Inhibitor A of [cyclin
      dependent] kinase 4-alternative reading frame (INK4A-ARF) and cyclin-dependent
      kinase 4, are involved in the regulation of cellular senescence, and possible
      reasons why this should be so. Based on the evidence including growth and
      survival kinetics of human and mouse melanocytes carrying germline deficiencies
      in the INK4A sequence, it is suggested that an 'M0' or p16/RB-dependent form of
      senescence may be particularly important in melanocytes. A speculative model is
      proposed, relating current concepts of early melanoma progression to the
      processes of cellular senescence and immortalization. This includes the
      suggestion that moles or nevi are senescent clones of melanocytes.

PMID- 12789282
TI  - Molecular plasticity of human melanoma cells.
AB  - The molecular analysis of tumors, such as melanoma, has benefited significantly
      from microarray technology that can facilitate the classification of tumors based
      on the differential expression of genes. The data summarized in this review
      describe the molecular profile of aggressive cutaneous and uveal melanoma cells
      as that of multiple phenotypes similar to a pluripotent, embryonic-like stem
      cell. A noteworthy example of the plasticity of the aggressive melanoma cell
      phenotype is demonstrated by the ability of these tumor cells to engage in
      vasculogenic mimicry and neovascularization. A review of the current evidence
      demonstrating important cellular and molecular determinants of melanoma
      vasculogenic mimicry is presented. In addition, novel signaling pathways are
      discussed, involving VE-cadherin, EphA2, FAK, and PI 3-kinase, which promote cell
      migration, invasion, and matrix remodeling. The observations summarized in this
      review describe some of the key molecular events that regulate the process of
      melanoma vasculogenic mimicry and identify new signal transduction pathways that
      can serve as putative targets for therapeutic intervention.

PMID- 12789283
TI  - Gene-expression profiling in human cutaneous melanoma.
AB  - Genomic technology presents new and exciting opportunities to study complex human
      diseases. Several types of genomic analysis are helping to elucidate the biology
      of important human cancers. One of these, gene expression profiling, provides a
      more comprehensive view of the consequences of the genetic changes in cancer
      cells than was previously available. In addition to detailing the expression
      patterns of thousands of genes simultaneously, this exploding field of research
      has begun to build a new 'molecular taxonomy' of cancer and to identify novel
      disease genes for many human cancers, including cutaneous melanoma. Whether this
      new information will lead to improved treatments and prolonged survival for
      cancer patients remains to be determined. Here, we review the use of
      complementary DNA microarray technology to study gene expression patterns in
      cutaneous melanoma and highlight recent advances concerning the identification of
      novel melanoma disease-related genes. The fundamentals of microarray technology
      and analysis have been extensively discussed, and readers are referred to several
      recent reviews in this area.

PMID- 12789284
TI  - Understanding the progression of melanocytic neoplasia using genomic analysis:
      from fields to cancer.
AB  - Analysis of DNA copy number changes using comparative genomic hybridization in
      melanocytic neoplasms has revealed distinct patterns of chromosomal aberrations
      between benign melanocytic nevi and melanoma. Whereas the vast majority of
      melanoma expresses chromosomal aberrations, blue nevi, congenital nevi, and most
      Spitz nevi typically show no aberrations. A subset of Spitz nevi shows an
      isolated gain of chromosome 11p, an aberration pattern not observed in melanoma.
      These Spitz nevi frequently harbor mutations in the HRAS gene located on this
      chromosomal arm. Comparisons among melanoma types showed that melanomas of the
      palms, soles, and subungual sites can be distinguished by the presence of
      multiple gene amplifications that arise very early in their progression. About
      50% of these amplifications are found at the cyclin D1 locus. By contrast,
      amplifications are significantly less frequent in other cutaneous melanoma types
      and if present arise late in progression. The frequent amplifications in
      melanomas on acral sites allowed the detection of single basal melanocytes with
      gene amplifications in the histologically normal appearing skin immediately
      adjacent to a melanoma. These "field cells" represent subtle melanoma in situ and
      are likely to represent minimal residual disease that can lead to local
      recurrences if not excised with safety margins. The high frequency of chromosomal
      aberrations in melanomas and their relative absence in nevi could indicate that
      melanocytes of melanomas went through telomeric crisis, whereas melanocytes in
      nevi did not. Such a scenario would suggest that replicative senescence is a
      tumor-suppressive mechanism in melanocytic neoplasia. It might also explain part
      of the phenomenon of regression commonly seen in melanoma. Genomic analysis is a
      powerful tool to obtain insight in the progression of melanocytic neoplasms with
      potential clinical applications for classification and detection of minimal
      residual melanoma.

PMID- 12789286
TI  - The INK4a/ARF locus and melanoma.
AB  - Inactivation of the INK4a/ARF (or CDKN2a) locus is a common and critical genetic
      event in the development of human and mouse melanoma. This locus engages the Rb
      and p53 tumor suppressor pathways through its capacity to encode two distinct
      gene products, p16(INK4a) and p14(ARF). This review highlights the body of
      evidence supporting a role for both p16(INK4a) and p14(ARF) in the suppression of
      melanoma, and speculates as to why this locus is preferentially targeted in this
      tumor type. In addition, the potential importance of these two pathways in
      mediating UV-induced melanoma genesis will be addressed via genetic and molecular
      evidence in the mouse.

PMID- 12789285
TI  - Oncogenes in melanoma.
AB  - Transformation of normal melanocytes into melanoma cells is accomplished by the
      activation of growth stimulatory pathways, typically leading to cellular
      proliferation, and the inactivation of apoptotic and tumor suppressor pathways.
      Small molecule inhibitors of proteins in the growth stimulatory pathways are
      under active investigation, and their application to melanoma patients would
      represent a new treatment strategy to inhibit cell proliferation or induce cell
      death. We provide a general overview of the mechanisms of oncogene activation and
      the functions of oncogenes. Lastly, we review oncogenic events in melanoma.

PMID- 12789287
TI  - Ultraviolet radiation and cutaneous malignant melanoma.
AB  - Recent years have seen a steady rise in the incidence of cutaneous malignant
      melanoma worldwide. Although it is now appreciated that the key to understanding
      the process by which melanocytes are transformed into malignant melanoma lies in
      the interplay between genetic factors and the ultraviolet (UV) spectrum of
      sunlight, the nature of this relation has remained obscure. Recently, prospects
      for elucidating the molecular mechanisms underlying such gene-environment
      interactions have brightened considerably through the development of UV
      responsive experimental animal models of melanoma. Genetically engineered mice
      and human skin xenografts constitute novel platforms upon which to build studies
      designed to elucidate the pathogenesis of UV-induced melanomagenesis. The future
      refinement of these in vivo models should provide a wealth of information on the
      cellular and genetic targets of UV, the pathways responsible for the repair of UV
      induced DNA damage, and the molecular interactions between melanocytes and other
      skin cells in response to UV. It is anticipated that exploitation of these model
      systems will contribute significantly toward the development of effective
      approaches to the prevention and treatment of melanoma.

PMID- 12789288
TI  - PTEN signaling pathways in melanoma.
AB  - Phosphatase and tensin homolog deleted in from chromosome ten (PTEN), initially
      also known as mutated in multiple advanced cancers or TGF-beta-regulated and
      epithelia cell-enriched phosphatase, is a tumor suppressor gene that is mutated
      in a large fraction of human melanomas. A broad variety of human cancers carry
      PTEN alterations, including glioblastomas, endometrial, breast, thyroid and
      prostate cancers. The PTEN protein has at least two biochemical functions: it has
      both lipid phosphatase and protein phosphatase activity. The lipid phosphatase
      activity of PTEN decreases intracellular PtdIns(3,4,5)P(3) level and downstream
      Akt activity. Cell-cycle progression is arrested at G1/S, mediated at least
      partially through the upregulation of the cyclin-dependent kinase inhibitor p27.
      In addition, agonist-induced apoptosis is mediated by PTEN, through the
      upregulation of proapoptotic machinery involving caspases and BID, and the
      downregulation of antiapoptotic proteins such as Bcl2. The protein phosphatase
      activity of PTEN is apparently less central to its involvement in tumorigenesis.
      It is involved in the inhibition of focal adhesion formation, cell spreading and
      migration, as well as the inhibition of growth factor-stimulated MAPK signaling.
      Therefore, the combined effects of the loss of PTEN lipid and protein phosphatase
      activity may result in aberrant cell growth and escape from apoptosis, as well as
      abnormal cell spreading and migration. In melanoma, PTEN loss has been mostly
      observed as a late event, although a dose-dependent loss of PTEN protein and
      function has been implicated in early stages of tumorigenesis as well. In
      addition, loss of PTEN and oncogenic activation of RAS seem to occur in a
      reciprocal fashion, both of which could cooperate with CDKN2A loss in
      contribution to melanoma tumorigenesis.

PMID- 12789289
TI  - Role and regulation of the thrombin receptor (PAR-1) in human melanoma.
AB  - To determine treatment strategies and predict the clinical outcome of patients
      with melanoma it is important to understand the etiology of this disease.
      Recently, there has been some insight into molecular basis of melanoma including
      identification of a few of the regulatory factors and genes involved in this
      disease. For instance, the transcription factor AP-2 plays a tumor suppressor
      like role in melanoma progression by regulating genes involved in tumor growth
      and metastasis. Previously, we have shown that the progression of human melanoma
      to the metastatic phenotype is associated with loss of AP-2 expression and
      deregulation of target genes such as MUC18/MCAM, c-KIT, and MMP-2. Increasing
      evidence demonstrates that the thrombin receptor (protease-activated receptor-1,
      PAR-1) plays a major role in tumor invasion and contributes to the metastatic
      phenotype of human melanoma. This review focuses on the role of the thrombin
      receptor in melanoma and its regulation by AP-2. We show that loss of AP-2
      expression in metastatic melanoma cells correlates with overexpression of the
      thrombin receptor. Our analysis of AP-2/Sp1 complexes within the regulatory
      region of the thrombin receptor demonstrates that AP-2 binds the proximal 3'
      region of the promoter and diminishes PAR-1 expression. Levels of AP-2 and Sp1
      proteins in a panel of melanoma cell lines demonstrated a marked decrease in the
      ratio of AP-2/Sp1, a decrease that correlated with overexpression of PAR-1 in
      metastatic melanoma cells. We propose that loss of AP-2 results in increased
      expression of the thrombin receptor, which subsequently contributes to the
      metastatic phenotype of melanoma by upregulating the expression of adhesion
      molecules, proteases, and angiogenic molecules.

PMID- 12789290
TI  - Apoptosis and melanoma chemoresistance.
AB  - Melanoma is the most aggressive form of skin cancer and is notoriously resistant
      to all current modalities of cancer therapy. A large set of genetic, functional
      and biochemical studies suggest that melanoma cells become 'bullet proof' against
      a variety of chemotherapeutic drugs by exploiting their intrinsic resistance to
      apoptosis and by reprogramming their proliferation and survival pathways during
      melanoma progression. In recent years, the identification of molecules involved
      in the regulation and execution of apoptosis, and their alteration in melanoma,
      have provided new insights into the molecular basis for melanoma chemoresistance.
      With this knowledge in hand, the challenge is now to devise strategies potent
      enough to compensate or bypass these cell death defects and improve the actual
      poor prognosis of patients at late stages of the disease.

PMID- 12789291
TI  - Death receptors and melanoma resistance to apoptosis.
AB  - Impaired ability to undergo programmed cell death in response to a wide range of
      external stimuli acquires melanomas a selective advantage for progression and
      metastasis as well as their notorious resistance to therapy. Better understanding
      of mechanisms that govern apoptosis has enabled identification of diverse routes
      by which melanomas manage to escape stimuli of apoptosis. Changes at genomic,
      transcriptional and post-translational levels of G-proteins and protein kinases
      (Ras, B-Raf) and their transcription factor effectors (c-Jun, ATF2, Stat3 and NF
      kappaB) affects TNF, Fas and TRAIL receptors, which play important roles in
      acquiring melanoma's resistance to apoptosis. Here, we summarize our current
      understanding of changes that alters the regulation of death receptors during
      melanoma development.

PMID- 12789292
TI  - Function and regulation of melanoma-stromal fibroblast interactions: when seeds
      meet soil.
AB  - Melanoma development and progression not only involve genetic and epigenetic
      changes that take place within the melanocytic cells, but also involve processes
      that are determined collectively by contextual factors including intercellular
      adhesions and communications. In this review, we focus on melanoma-stromal
      fibroblast crosstalk by direct cell-cell contact and by growth
      factors/cytokines/chemokines interacting with their respective receptors. The
      interactions between melanoma cells and stromal fibroblasts create a context that
      promotes tumor growth, migration/invasion, and angiogenesis. An understanding of
      this process and developing new experimental and screening models are of great
      importance for the development of effective therapeutical strategies to treat
      melanoma.

PMID- 12789293
TI  - Angiogenesis, lymphangiogenesis, and melanoma metastasis.
AB  - The induction of angiogenesis is a critical point in the development of most
      human tumors - including melanomas. Some of the earliest studies in the field of
      tumor angiogenesis showed that transplantation of human melanoma fragments into
      the hamster cheek pouch stimulated blood vessel growth. Since then, numerous
      studies have demonstrated that human melanomas also induce angiogenesis. The
      prognostic importance of the degree of melanoma vascularization, however, has
      remained controversial. Elevated expression of several angiogenic factors,
      including vascular endothelial growth factor, basic fibroblast growth factor, and
      interleukin-8, has been detected in primary cutaneous melanomas, and the
      importance of these mediators in promoting melanoma angiogenesis and metastasis
      has been confirmed in tumor xenotransplant models. Based upon these findings,
      several clinical trials of angiogenesis inhibitors have been initiated in human
      melanoma patients and are currently underway. Recent experimental evidence
      indicates that tumor-associated lymphangiogenesis also plays an important role in
      mediating tumor spread to regional lymph nodes. These observations have important
      implications for prognosis and treatment of human melanomas.

PMID- 12789294
TI  - Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity.
AB  - Cancer cells express self-antigens that are weakly recognized by the immune
      system. Even though responses against autologous cells are difficult to induce,
      the immune system is still able to mount a response against cancer. The discovery
      of the molecular identity of antigens that are recognized by the immune system of
      melanoma patients has led to the elucidation of tumor immunity at a cellular and
      molecular level. Multiple pathways in both the priming and effector phases of
      melanoma rejection have been described. Animal models' active immunotherapies for
      melanoma show a requirement for the cellular compartment of the immune system in
      the priming phase, primarily CD4+T cells. More diverse elements are required for
      the effector phase, including components from the innate immune system
      (macrophages, complement and/or natural killer cells) and from the adaptive
      immune system (CD8+T cells and B cells). Minor differences in amino-acid
      sequences of antigens must determine the particular mechanisms involved in tumor
      rejection. Since the immune system contains T and B cells that recognize and
      reject autologous cells, a consequence of tumor immunity is potential
      autoimmunity. There are distinct pathways for tumor immunity and autoimmunity.
      The requirements for autoimmunity at the priming phase seem to be CD4+/IFN-gamma
      dependent while the effector mechanisms are alternative and redundant. Vitiligo
      (autoimmune hypopigmentation) can be mediated by T cells, FcgammaR+macrophages
      and/or complement.

PMID- 12789295
TI  - GM-CSF-secreting melanoma vaccines.
AB  - The development of biochemical and genetic schemes to characterize cancer
      antigens led to the recognition that malignant melanoma frequently evokes a host
      response. While the generation of brisk T-cell infiltrates in early stage disease
      is correlated with prolonged survival, host reactions in most cases are
      insufficient to impede tumor progression. One variable that may limit the potency
      of the host response against nascent melanoma is the mixture of cytokines present
      in the tumor microenvironment. In a murine melanoma model, we identified
      granulocyte-macrophage colony stimulating factor (GM-CSF) as the most potent
      molecule for augmenting tumor immunity following gene transfer into melanoma
      cells. Vaccination with irradiated melanoma cells engineered to secrete GM-CSF
      enhances host responses through improved tumor antigen presentation by recruited
      dendritic cells and macrophages. Melanoma-specific CD4(+) and CD8(+) T-cells,
      CD1d-restricted NKT-cells, and antibodies mediate tumor rejection. Initial
      testing of this immunization strategy in patients with metastatic melanoma
      revealed the consistent induction of cellular and humoral antitumor responses
      that provoked the extensive necrosis of distant metastases without significant
      toxicity.

PMID- 12789296
TI  - Biodefence takes its toll.

PMID- 12789297
TI  - A meeting for Europe's scientists and publics.

PMID- 12789298
TI  - Harmful potential of viral vectors fuels doubts over gene therapy.

PMID- 12789299
TI  - Protests win reprieve for renowned medical lab.

PMID- 12789300
TI  - Divisions sink US consensus effort on transgenic food.

PMID- 12789301
TI  - UK universities face star treatment in funding revamp.

PMID- 12789302
TI  - Natural history collections in crisis as funding is slashed.

PMID- 12789303
TI  - Biologist gets minimum sentence in 'espionage' case.

PMID- 12789304
TI  - Geneticists play the numbers game in vain.

PMID- 12789305
TI  - Pet theory comes to the fore in fight against SARS.

PMID- 12789306
TI  - Panel calls for sea change to fisheries policy.

PMID- 12789307
TI  - Japanese team makes stem cells.

PMID- 12789309
TI  - Sweet revenge.

PMID- 12789310
TI  - The ulcer bug: Gut reaction.

PMID- 12789311
TI  - SARS, a challenge from the South.

PMID- 12789312
TI  - Impact factors: target the funding bodies.

PMID- 12789318
TI  - Neurobiology: All change at the synapse.

PMID- 12789319
TI  - Biogeochemistry: Ancient oceans and oxygen.

PMID- 12789320
TI  - Cancer: Out of air is not out of action.

PMID- 12789322
TI  - Condensed-matter physics: Hydrogen falls into line.

PMID- 12789323
TI  - Signal transduction: A regulator branches out.

PMID- 12789325
TI  - The double puzzle of diabetes.

PMID- 12789326
TI  - Palaeobotany: Ice-age steppe vegetation in east Beringia.

PMID- 12789327
TI  - Insect behaviour: Motion camouflage in dragonflies.

PMID- 12789328
TI  - Electromagnetic waves: Negative refraction by photonic crystals.

PMID- 12789329
TI  - Social networks: Sexual contacts and epidemic thresholds.

PMID- 12789331
TI  - Three modes of synaptic vesicular recycling revealed by single-vesicle imaging.
AB  - Synapses recycle their spent vesicles in order to keep up with on-going
      neurotransmitter release. To investigate vesicle recycling in the small synapses
      of hippocampal neurons, we have used an optical recording method that permits us
      to resolve single-vesicle events. Here we show that an exocytic event can
      terminate with three modes of vesicle retrieval: a fast (400-860 ms) 'kiss-and
      run' mode that has a selective fusion pore; a slow (8-21 s) 'compensatory' mode;
      and a 'stranded' mode of recycling, in which a vesicle is left on the cell
      surface until a nerve impulse triggers its retrieval. We have also observed that,
      in response to a nerve impulse, synapses with low release probability primarily
      use the kiss-and-run mode, whereas high release probability terminals
      predominantly use the compensatory mode of vesicle retrieval.

PMID- 12789332
TI  - An extragalactic supernebula confined by gravity.
AB  - Little is known about the origins of globular clusters, which contain hundreds of
      thousands of stars in a volume only a few light years across. Radiation pressure
      and winds from luminous young stars should disperse the star-forming gas and
      disrupt the formation of the cluster. Globular clusters in our Galaxy cannot
      provide answers; they are billions of years old. Here we report the measurement
      of infrared hydrogen recombination lines from a young, forming super star cluster
      in the dwarf galaxy NGC5253. The lines arise in gas heated by a cluster of about
      one million stars, including 4,000-6,000 massive, hot 'O' stars. It is so young
      that it is still enshrouded in gas and dust, hidden from optical view. The gases
      within the cluster seem bound by gravity, which may explain why the windy and
      luminous O stars have not yet blown away those gases. Young clusters in
      'starbursting' galaxies in the local and distant Universe may also be
      gravitationally confined and cloaked from view.

PMID- 12789333
TI  - A strong decrease in Saturn's equatorial jet at cloud level.
AB  - The atmospheres of the giant planets Jupiter and Saturn have a puzzling system of
      zonal (east-west) winds alternating in latitude, with the broad and intense
      equatorial jets on Saturn having been observed previously to reach a velocity of
      about 470 m x s(-1) at cloud level. Globally, the location and intensity of
      Jupiter's jets are stable in time to within about ten per cent, but little is
      known about the stability of Saturn's jet system. The long-term behaviour of
      these winds is an important discriminator between models for giant-planet
      circulations. Here we report that Saturn's winds show a large drop in the
      velocity of the equatorial jet of about 200 m x s(-1) from 1996 to 2002. By
      contrast, the other measured jets (primarily in the southern hemisphere) appear
      stable when compared to the Voyager wind profile of 1980-81.

PMID- 12789334
TI  - Universal alignment of hydrogen levels in semiconductors, insulators and
      solutions.
AB  - Hydrogen strongly affects the electronic and structural properties of many
      materials. It can bind to defects or to other impurities, often eliminating their
      electrical activity: this effect of defect passivation is crucial to the
      performance of many photovoltaic and electronic devices. A fuller understanding
      of hydrogen in solids is required to support development of improved hydrogen
      storage systems, proton-exchange membranes for fuel cells, and high-permittivity
      dielectrics for integrated circuits. In chemistry and in biological systems,
      there have also been many efforts to correlate proton affinity and deprotonation
      with host properties. Here we report a systematic theoretical study (based on ab
      initio methods) of hydrogen in a wide range of hosts, which reveals the existence
      of a universal alignment for the electronic transition level of hydrogen in
      semiconductors, insulators and even aqueous solutions. This alignment allows the
      prediction of the electrical activity of hydrogen in any host material once some
      basic information about the band structure of that host is known. We present a
      physical explanation that connects the behaviour of hydrogen to the line-up of
      electronic band structures at heterojunctions.

PMID- 12789335
TI  - Chaperonin-mediated stabilization and ATP-triggered release of semiconductor
      nanoparticles.
AB  - Various properties of semiconductor nanoparticles, including photoluminescence
      and catalytic activity, make these materials attractive for a range of
      applications. As nanoparticles readily coagulate and so lose their size-dependent
      properties, shape-persistent three-dimensional stabilizers that enfold
      nanoparticles have been exploited. However, such wrapping approaches also make
      the nanoparticles insensitive to external stimuli, and so may limit their
      application. The chaperonin proteins GroEL (from Escherichia coli) and T.th
      ('T.th cpn', from Thermus thermophilus HB8) encapsulate denatured proteins inside
      a cylindrical cavity; after refolding, the encapsulated proteins are released by
      the action of ATP inducing a conformational change of the cavity. Here we report
      that GroEL and T.th cpn can also enfold CdS semiconductor nanoparticles, giving
      them high thermal and chemical stability in aqueous media. Analogous to the
      biological function of the chaperonins, the nanoparticles can be readily released
      from the protein cavities by the action of ATP. We expect that integration of
      such biological mechanisms into materials science will open a door to
      conceptually new bioresponsive devices.

PMID- 12789336
TI  - Evidence for low sulphate and anoxia in a mid-Proterozoic marine basin.
AB  - Many independent lines of evidence document a large increase in the Earth's
      surface oxidation state 2,400 to 2,200 million years ago, and a second biospheric
      oxygenation 800 to 580 million years ago, just before large animals appear in the
      fossil record. Such a two-staged oxidation implies a unique ocean chemistry for
      much of the Proterozoic eon, which would have been neither completely anoxic and
      iron-rich as hypothesized for Archaean seas, nor fully oxic as supposed for most
      of the Phanerozoic eon. The redox chemistry of Proterozoic oceans has important
      implications for evolution, but empirical constraints on competing environmental
      models are scarce. Here we present an analysis of the iron chemistry of shales
      deposited in the marine Roper Basin, Australia, between about 1,500 and 1,400
      million years ago, which record deep-water anoxia beneath oxidized surface water.
      The sulphur isotopic compositions of pyrites in the shales show strong variations
      along a palaeodepth gradient, indicating low sulphate concentrations in mid
      Proterozoic oceans. Our data help to integrate a growing body of evidence
      favouring a long-lived intermediate state of the oceans, generated by the early
      Proterozoic oxygen revolution and terminated by the environmental transformation
      late in the Proterozoic eon.

PMID- 12789337
TI  - Stability of forest biodiversity.
AB  - Two hypotheses to explain potentially high forest biodiversity have different
      implications for the number and kinds of species that can coexist and the
      potential loss of biodiversity in the absence of speciation. The first hypothesis
      involves stabilizing mechanisms, which include tradeoffs between species in terms
      of their capacities to disperse to sites where competition is weak, to exploit
      abundant resources effectively and to compete for scarce resources. Stabilization
      results because competitors thrive at different times and places. An alternative,
      'neutral model' suggests that stabilizing mechanisms may be superfluous. This
      explanation emphasizes 'equalizing' mechanisms, because competitive exclusion of
      similar species is slow. Lack of ecologically relevant differences means that
      abundances experience random 'neutral drift', with slow extinction. The relative
      importance of these two mechanisms is unknown, because assumptions and
      predictions involve broad temporal and spatial scales. Here we demonstrate that
      predictions of neutral drift are testable using palaeodata. The results
      demonstrate strong stabilizing forces. By contrast with the neutral prediction of
      increasing variance among sites over time, we show that variances in post-Glacial
      tree abundances among sites stabilize rapidly, and abundances remain coherent
      over broad geographical scales.

PMID- 12789338
TI  - Scaling metabolism from organisms to ecosystems.
AB  - Understanding energy and material fluxes through ecosystems is central to many
      questions in global change biology and ecology. Ecosystem respiration is a
      critical component of the carbon cycle and might be important in regulating
      biosphere response to global climate change. Here we derive a general model of
      ecosystem respiration based on the kinetics of metabolic reactions and the
      scaling of resource use by individual organisms. The model predicts that fluxes
      of CO2 and energy are invariant of ecosystem biomass, but are strongly influenced
      by temperature, variation in cellular metabolism and rates of supply of limiting
      resources (water and/or nutrients). Variation in ecosystem respiration within
      sites, as calculated from a network of CO2 flux towers, provides robust support
      for the model's predictions. However, data indicate that variation in annual flux
      between sites is not strongly dependent on average site temperature or latitude.
      This presents an interesting paradox with regard to the expected temperature
      dependence. Nevertheless, our model provides a basis for quantitatively
      understanding energy and material flux between the atmosphere and biosphere.

PMID- 12789339
TI  - Single synaptic vesicles fusing transiently and successively without loss of
      identity.
AB  - Vesicle fusion and recycling are particularly critical for ongoing
      neurotransmitter release in the small nerve terminals of the brain, which
      typically contain about 30 functional vesicles. However, the modes of exocytosis
      and endocytosis that operate at synapses of the central nervous system are
      incompletely understood. Here we show real-time visualization of a single vesicle
      fusing at a small synapse of the central nervous system, made possible by highly
      intensified charge-coupled device imaging of hippocampal synaptic terminals, in
      which a single vesicle was labelled with the fluorescent membrane marker FM1-43
      (ref. 6). In a small number of cases, full loss of fluorescent membrane dye was
      elicited by a single action potential, consistent with classical complete
      collapse. In most cases, however, action potentials triggered only partial loss
      of fluorescence, suggesting vesicular retention of membrane marker, consistent
      with 'kiss-and-run' vesicle cycling. An alternative hypothesis of independent
      fusion of partially stained vesicles arising from endosomal splitting could be
      excluded by observations on the size and timing of successive fusion events.
      Thus, our experimental evidence supports a predominance of kiss-and-run fusion
      events and rapid vesicular re-use.

PMID- 12789340
TI  - Fission yeast mod5p regulates polarized growth through anchoring of tea1p at cell
      tips.
AB  - Microtubules have a central role in eukaryotic cell polarity, in part through
      interactions between microtubule end-binding proteins and the cell cortex. In the
      fission yeast Schizosaccharomyces pombe, microtubules and the polarity modulator
      tea1p maintain cylindrical cell shape and strictly antipodal cell growth. The
      tea1p protein is transported to cell tips by association with growing microtubule
      plus ends; once at cell tips, tea1p releases from microtubule ends and associates
      with the cell cortex, where it coordinates polarized growth. Here we describe a
      cortical protein, mod5p, that regulates the dynamic behaviour of tea1p. In
      mod5Delta cells, tea1p is efficiently transported on microtubules to cell tips
      but fails to anchor properly at the cortex and thus fails to accumulate to normal
      levels. mod5p contains a signal for carboxy-terminal prenylation and in wild-type
      cells is associated with the plasma membrane at cell tips. However, in tea1Delta
      cells, although mod5p remains localized to the plasma membrane, mod5p is no
      longer restricted to the cell tips. We propose that tea1p and mod5p act in a
      positive-feedback loop in the microtubule-mediated regulation of cell polarity.

PMID- 12789341
TI  - Sphingolipid signalling in Arabidopsis guard cells involves heterotrimeric G
      proteins.
AB  - In animals, the sphingolipid metabolite sphingosine-1-phosphate (S1P) functions
      as both an intracellular messenger and an extracellular ligand for G-protein
      coupled receptors of the S1P receptor family, regulating diverse biological
      processes ranging from cell proliferation to apoptosis. Recently, it was
      discovered in plants that S1P is a signalling molecule involved in abscisic acid
      (ABA) regulation of guard cell turgor. Here we report that the enzyme responsible
      for S1P production, sphingosine kinase (SphK), is activated by ABA in Arabidopsis
      thaliana, and is involved in both ABA inhibition of stomatal opening and
      promotion of stomatal closure. Consistent with this observation, inhibition of
      SphK attenuates ABA regulation of guard cell inward K(+) channels and slow anion
      channels, which are involved in the regulation of stomatal pore size.
      Surprisingly, S1P regulates stomatal apertures and guard cell ion channel
      activities in wild-type plants, but not in knockout lines of the sole
      prototypical heterotrimeric G-protein alpha-subunit gene, GPA1 (refs 5, 6, 7-8).
      Our results implicate heterotrimeric G proteins as downstream elements in the S1P
      signalling pathway that mediates ABA regulation of stomatal function, and suggest
      that the interplay between S1P and heterotrimeric G proteins represents an
      evolutionarily conserved signalling mechanism.

PMID- 12789342
TI  - Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene
      expression.
AB  - Cytokine-induced activation of the IkappaB kinases (IKK) IKK-alpha and IKK-beta
      is a key step involved in the activation of the NF-kappaB pathway. Gene
      disruption studies of the murine IKK genes have shown that IKK-beta, but not IKK
      alpha, is critical for cytokine-induced IkappaB degradation. Nevertheless, mouse
      embryo fibroblasts deficient in IKK-alpha are defective in the induction of NF
      kappaB-dependent transcription. These observations raised the question of whether
      IKK-alpha might regulate a previously undescribed step to activate the NF-kappaB
      pathway that is independent of its previously described cytoplasmic role in the
      phosphorylation of IkappaBalpha. Here we show that IKK-alpha functions in the
      nucleus to activate the expression of NF-kappaB-responsive genes after
      stimulation with cytokines. IKK-alpha interacts with CREB-binding protein and in
      conjunction with Rel A is recruited to NF-kappaB-responsive promoters and
      mediates the cytokine-induced phosphorylation and subsequent acetylation of
      specific residues in histone H3. These results define a new nuclear role of IKK
      alpha in modifying histone function that is critical for the activation of NF
      kappaB-directed gene expression.

PMID- 12789344
TI  - Food for thought.

PMID- 12789345
TI  - For scientists who want a career in law, the options are greater than ever--and
      some don't even involve going back to school.

PMID- 12789343
TI  - A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene
      expression.
AB  - NF-kappaB is a principal transcriptional regulator of diverse cytokine-mediated
      processes and is tightly controlled by the IkappaB kinase complex (IKK
      alpha/beta/gamma). IKK-beta and IKK-gamma are critical for cytokine-induced NF
      kappaB function, whereas IKK-alpha is thought to be involved in other regulatory
      pathways. However, recent data suggest a role for IKK-alpha in NF-kappaB
      dependent gene expression in response to cytokine treatment. Here we demonstrate
      nuclear accumulation of IKK-alpha after cytokine exposure, suggesting a nuclear
      function for this protein. Consistent with this, chromatin immunoprecipitation
      (ChIP) assays reveal that IKK-alpha was recruited to the promoter regions of NF
      kappaB-regulated genes on stimulation with tumour-necrosis factor-alpha. Notably,
      NF-kappaB-regulated gene expression is suppressed by the loss of IKK-alpha and
      this correlates with a complete loss of gene-specific phosphorylation of histone
      H3 on serine 10, a modification previously associated with positive gene
      expression. Furthermore, we show that IKK-alpha can directly phosphorylate
      histone H3 in vitro, suggesting a new substrate for this kinase. We propose that
      IKK-alpha is an essential regulator of NF-kappaB-dependent gene expression
      through control of promoter-associated histone phosphorylation after cytokine
      exposure. These findings provide additional insight into the role of the IKK
      complex in NF-kappaB-regulated gene expression.

PMID- 12789346
TI  - Abstracts of the 12th European Congress on Obesity. Helsinki, Finland, 29 May-1
      June, 2003.
AB  - International Journal of Obesity (2003) 27, S1. doi:10.1038/sj.ijo.0802329

PMID- 12789383
TI  - Spread sexual medicine knowledge through the written word: IJIRjsm.

PMID- 12789384
TI  - A double-blind, randomised- placebo, controlled, parallel group, multicentre,
      flexible-dose escalation study to assess the efficacy and safety of sildenafil
      administered as required to male outpatients with erectile dysfunction in Korea.
AB  - The efficacy and safety of sildenafil was evaluated in a randomiSed, double
      blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with
      erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months
      duration. A total of 133 patients were randomised at six centres in Korea to
      receive either sildenafil (50 mg initially, increased if necessary to l00 mg or
      decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching
      placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual
      activity for a period of 8 weeks. At the end of this time, the primary efficacy
      variables relating to the achievement and maintenance of erections sufficient for
      sexual intercourse, and the secondary efficacy variables, which included: (1) the
      five separate domains of sexual functioning of the International Index of
      Erectile Function (IIEF) scale, (2) the percentage of successful intercourse
      attempts, and (3) a global assessment of erections, were all statistically
      significantly improved by sildenafil in comparison with placebo (P&<0.0001).
      Treatment-related adverse events occurred in 56.1% of patients receiving
      sildenafil and 20.9% receiving placebo. The most common adverse events with
      sildenafil were vasodilatation (flushing), headache and abnormalities in colour
      vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in
      nature. The efficacy and safety of sildenafil in this population of Korean men
      appears similar to that reported in other studies in western populations.

PMID- 12789385
TI  - Under-reporting of erectile dysfunction among men with unrelated urologic
      conditions.
AB  - To evaluate the incidence of erectile dysfunction (ED) in men with unrelated
      urologic conditions paying special attention to the reasons for patient under
      reporting. We asked 500 consecutive men over age 50 visiting their urologist's
      office for problems unrelated to ED, whether or not they had any difficulty with
      their potency. Those who gave a positive response were then asked to complete a
      questionnaire to assess their reasons for under-reporting and whether they had
      had any previous discussions with their primary-care physicians regarding their
      sexual function. Out of 500 men, 218 (44%) reported experiencing some degree of
      ED. Reasons for failure to discuss ED with their urologist included: 161 out of
      218 (74%) were embarrassed; 27 out of 218 (12%) felt that ED was a natural part
      of aging; 20 out of 218 (9%) were unaware that urologists dealt with the problem
      of ED; and 10 out of 218 (5%) did not consider the problem worthy of attention.
      Only 48 of the 218 men with ED reported having previous discussions about their
      problem with their primary-care physicians. Of the 170 patients who did not
      report having such discussions, 140 (82%) reported that they would have liked
      their primary-care physician to have initiated a discussion of ED during their
      routine visits. In conclusion. a significant percentage of older men with some
      unrelated urologic complaint also suffer from some degree of ED and remain
      undiagnosed unless specifically questioned about this problem. By far, the most
      common reason for under-reporting of ED was patient embarrassment. While
      urologists are able to elicit information regarding erectile function on specific
      questioning, patients appear comfortable and willing to discuss their potency
      with primary-care physicians.

PMID- 12789386
TI  - Vardenafil reverses erectile dysfunction induced by paroxetine in rats.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are associated with a high
      incidence of impotence. Paroxetine is an extensively used SSRI that has been
      shown to impair erectile function in patients, to induce erectile dysfunction and
      to inhibit nitric oxide synthase (NOS) activity and NO production in animal
      models. NO is a key mediator of penile erection. Vardenafil is a type 5
      phosphodiesterase inhibitor that potentiates NO-mediated responses in isolated
      trabecular smooth muscle and penile erection in men in clinical trials. The aim
      of this study was to evaluate the effects of vardenafil on the impairment of
      erectile responses produced by paroxetine in the rat model. Application of
      cavernosal nerve electrical stimulation (CNES) produced frequency-related
      intracavernosal pressure (ICP) increases, which were inhibited by the NOS
      inhibitor N(G)-nitro-L-arginine (0.3 mg/kg) and potentiated by vardenafil (0.3
      mg/kg). Acute paroxetine treatment (10 mg/kg) significantly reduced ICP-responses
      to CNES. This inhibition was completely reversed by vardenafil (0.3 mg/kg)
      administration. The results show that the erectile dysfunction induced by
      paroxetine in rats can be effectively treated with vardenafil, suggesting that
      the use of this compound could be a reasonable therapeutic approach to treating
      erectile dysfunction associated with SSRI administration.

PMID- 12789387
TI  - Clinical course of penile fibrosis in intracavernosal prostaglandin E1 injection
      therapy: a follow-up of 44 patients.
AB  - A study was undertaken of 44 patients who had developed fibrotic changes in the
      penis in the course of intracavernosal prostaglandin E1 (PGE1) injection therapy
      for erectile dysfunction. Of these patients, 75.0% (n=33) were followed up for
      more than 24 months, and 59.1% (n=26) for more than 36 months. Of the patients,
      52.3% (n=23) had clinical improvement of the fibrotic changes without therapeutic
      intervention and despite most (91.3%) continuing intracavernosal PGE1 injection
      therapy. These included 25.0% (n=11) no longer having clinically detectable
      penile fibrosis (PF). The presence of penile curvature or pain did not
      significantly influence this outcome. The ages of men who showed improvement and
      the duration of their injection therapy were similar to those who did not
      improve. It would be prudent to defer therapeutic intervention for PF in the
      course of intracavernosal PGE1 injection therapy in anticipation of possible
      spontaneous improvement.

PMID- 12789388
TI  - Normal hemodynamic parameters do not always predict the presence of a rigid
      erection: a quantitative assessment of functional erectile impairment.
AB  - The purpose was to assess objectively and quantitatively the hemodynamic status
      and the degree of functional erectile impairment in a group of impotent patients.
      A clinical study was designed, incorporating pharmacocavernosometry (to evaluate
      arterial and veno-occlusive function) with axial buckling forces and penile
      geometry measurements in a group of impotent patients. The pressure gradient
      between the intracavernosal pressure associated with the presence of penile axial
      rigidity and the equilibrium intracavernosal pressure was calculated (axial
      rigidity gradient, ARG); such methodology allowed a quantitative characterization
      of functional impairment, as ARG expresses the intracavernosal pressure increase
      necessary to achieve axial rigidity and therefore potency. Penile geometry
      characteristics were also expressed by calculating the penile aspect ratio
      (diameter/length, D/L). In 83 consecutive patients tested (mean age 42.89+/
      9.96), rigidity occurred at intracavernosal pressures between 50 and 100 mm Hg. A
      conversely proportional relation was noticed between penile aspect ratio values
      and the intracavernosal pressure associated with rigidity values, clearly
      demonstrating the important functional role of penile geometry. ARG demonstrated
      a wide range of values (3-69 mm Hg), reflective of the severity of the erectile
      dysfunction on each patient. Half (50.6%) of the patients had ARG values < or =20
      mm Hg, indicative of minimal and minimal-to-moderate erectile impairment, while
      20.48% had ARG between 21-30 and 28.92% >30 mm Hg, indicative of moderate and
      severe erectile dysfunction (ED) respectively. In all, 6% of the study group, all
      of them with primary ED, ARG <20 mm Hg had normal hemodynamics, but low penile
      aspect ratio values indicating that penile geometry may be the cause of
      insufficient rigidity. Hemodynamic integrity is the most critical, but not the
      only determinant of penile rigidity, as erectile impairment may be noticed in
      patients with normal arterial inflow and corporal veno-occlusive function. In
      such cases, unfavorable penile geometry should be considered as the possible
      etiological factor of impotence.

PMID- 12789389
TI  - The ups and downs of Rho-kinase and penile erection: upstream regulators and
      downstream substrates of rho-kinase and their potential role in the erectile
      response.
AB  - In the absence of arousal stimuli, the activity of the Rho-kinase-mediated
      signaling pathway promotes vasoconstriction of the cavernosal arterioles and
      sinuses, keeping the penis in the nonerect state. Upon sexual arousal or during
      nocturnal tumescence, nitric oxide (NO), released from
      nonadrenergic/noncholinergic nerves or from local endothelial cells, induces
      cavernosal vasodilation, resulting in an elevation in blood flow and
      intracavernosal pressure to initiate the erectile response. Although NO is
      thought to be the principal stimulator of penile erection, the signaling
      mechanism(s) of NO-mediated cavernosal vasodilation is unknown. In this article,
      we will consider the novel hypothesis that NO induces penile erection through the
      inhibition of endogenous Rho-kinase-mediated vasoconstriction. Additionally, we
      will look downstream of Rho-kinase, introducing a potential role for various
      substrates in the mechanism of Rho-kinase-mediated constriction in the cavernosal
      vasculature.

PMID- 12789390
TI  - Predictive validity of the Golombok Rust Inventory of Sexual Satisfaction (GRISS)
      for the presence of sexual dysfunctions within a Dutch urological population.
AB  - The objective of this study was to investigate the predictive validity of the
      Dutch translation of the Golombok Rust Inventory of Sexual Satisfaction (GRISS)
      for the presence of clinically relevant sexual dysfunctions and patient's need of
      help. A total of 57 male urological outpatients (age 50.7+/-13.2 y; range 27-77
      y) completed the GRISS, a 28-item self-report questionnaire assessing sexual
      dysfunctions and sexual satisfaction in heterosexual relationships. GRISS
      subscales were found to differentiate multivariately between men with and without
      sexual dysfunctions. The erectile dysfunction (In the original English version of
      the GRISS, the term 'impotence' was used instead of 'erectile dysfunction'),
      dissatisfaction, and infrequency subscales also differentiated univariately
      between these groups. The predictive validity for the presence of sexual
      dysfunctions and for the patients' need for professional help was investigated.
      Prediction models, derived by means of logistic regression analysis, were tested
      in a crossvalidation sample. Sensitivity and specificity for the presence of
      sexual dysfunctions, as well as the predictive values positive and negative were
      found to be satisfactory. The predictive validity of the GRISS was found equally
      satisfactory for the patients' need for professional help. The discriminant and
      predictive validity of the GRISS in men with and without sexual dysfunctions
      appeared satisfactory. Routine use of the GRISS appears warranted for the
      screening of sexual dysfunctions in new urological patients.

PMID- 12789391
TI  - Effect of sildenafil on nocturnal erections of potent men.
AB  - We try to evaluate the effect of sildenafil on nocturnal penile erections of
      potent men. We recruited 22 potent men (eight medical students and 14 urology
      residents) 23-29 years old into the study. A disorder-free medical and sexual
      history and normal erectile functions were the only inclusion criteria. All
      subjects completed three sessions of consecutive nights using the RigiScan Plus
      device. After a first night of adaptation, night 2 recordings were their baseline
      values whereas they received sildenafil 100 mg on night 3. We observed
      statistically significant improvement with regard to those NPT parameters at the
      nights with sildenafil: number of erectile episodes; duration of tip rigidity
      >60%, RAU tip, RAU base and TAU tip (P<0.005). Although the duration of erectile
      episodes (min) and TAU base were greater during the sildenafil night, these did
      not reach statistical significance. In conclusion, our study showed that
      sildenafil can improve nocturnal erectile quality not only in patients with
      erectile dysfunction as previously published but also in potent males.

PMID- 12789392
TI  - Evidence for centrally initiated genital vasocongestive engorgement in the female
      rat: findings from a new model of female sexual arousal response.
AB  - PURPOSE: In spite of rapidly growing interest, few research tools have been
      developed to study female sexual dysfunction. Using the D(1)/D(2) agonist,
      apomorphine (APO), our objective was to develop a new model of the sexual arousal
      response in female rats based on one previously established for the male
      condition. METHODS: APO (80 micro g/kg, s.c.) was given during proestrus (P),
      estrus (E), metestrus (M), early diestrus (DI) and late diestrus (DII), and in
      ovariectomized (OVX) female Wistar rats. APO-induced behavioral and genital
      responses were characterized (30 min) using video monitoring. RESULTS: APO
      induced reproducible, periodic morphological changes in the external genitalia.
      The onset, timing and duration of these female APO responses were consistent with
      genital vasocongestive arousal (GVA) responses in males (ie erections). APO
      induced GVAs occurred throughout the estrous cycle, peaking in E (1.4+/-1.21
      overall; 0.9+/-0.64 in DII; 1.8+/-1.66 in E) and were markedly diminished by
      ovariectomy (OVX, 0.4+/-0.51). CONCLUSION: APO induced a reproducible sexual
      arousal response in female rats involving obvious genital vasocongestive
      engorgement. Further, the findings demonstrate that the APO-induced genital
      arousal responses are hormonally regulated.

PMID- 12789393
TI  - Isolation of two isoforms of phosphodiesterase 5 from rat penis.
AB  - Inhibition of cGMP-specific phosphodiesterase type 5 (PDE5) has been shown to
      improve penile erection in patients with erectile dysfunction. We have reported
      previously the cloning of three PDE5 isoforms from human penile tissues. Here we
      report the cloning of two PDE5 isoforms from rat penile tissues. The similarity
      between rat and human PDE5A1-specific sequences were 68 and 88% at the nucleotide
      and amino-acid levels, respectively. Like the bovine and canine PDE5A1 sequences,
      the rat PDE5A1 sequence lacks the polyglutamine tract that appears to be unique
      to the human PDE5A1 sequence. The similarity between rat and human PDE5A2
      specific sequences were 64 and 100% at the nucleotide and amino-acid levels,
      respectively. The equivalent of human PDE5A3-specific sequence was identified in
      the rat PDE5A gene; however, repeated efforts to clone the putative rat PDE5A3
      isoform were not successful. Expression of PDE5A1 and A2 mRNA in various tissues
      was examined by Northern blotting and reverse transcription-polymerase chain
      reaction. Results from the two experimental procedures were largely in good
      agreement and indicated that PDE5A1 and A2 mRNA were expressed in a tissue
      specific manner with PDE5A2 being the dominant isoform. International Journal of
      Impotence Research (2003) 15, 129-136. doi:10.1038/sj.ijir.3900983

PMID- 12789394
TI  - Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve
      stimulation in female dogs.
AB  - The relaxation of the smooth muscle in the vagina and clitoris and the increase
      of blood flow into these organs is thought to be essential in the female sexual
      response. Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that
      potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle
      relaxation and improving penile erection in men. Although the potentiation of the
      NO/cGMP pathway through PDE5 inhibitors can clearly enhance blood flow into the
      penis and is used in the therapy of male sexual dysfunction, there is controversy
      about the efficacy of these agents in improving female sexual function. The aim
      of this work was to evaluate the effects of vardenafil on the increase of blood
      flow into the vagina and clitoris induced by pelvic nerve electrical stimulation
      (PNES) in a female dog model. Application of PNES produced consistent and
      frequency-related increased blood flow into the vagina and clitoris of
      anesthetized female dogs. The magnitude and duration of the blood flow responses
      to PNES were variable among the different animals but remained stable over time
      within the same animal. The intravenous administration of vardenafil (1 mg/kg)
      significantly potentiated the increases in blood flow produced by PNES into the
      vagina (381.4 and 206.2% of control response at 5 and 10 Hz, respectively,
      P<0.01, n=6) and clitoris (379.4 and 238.5% of control response at 5 and 10 Hz,
      respectively, P<0.01, n=6) 20 min after administration. The significant
      enhancement of PNES-induced responses was maintained 50 min (224.5 and 181.0%,
      P<0.01 in vagina; 294.8 and 258.9%, P<0.05 in clitoris) and 80 min after
      vardenafil administration (209.5 and 156.9%, P<0.05 in vagina; 268.9 and 194.9%,
      P<0.05 in clitoris). Here we present a feasible model for research into female
      sexual function. Our results show that vardenafil effectively potentiates the
      blood flow responses to PNES in the genitalia of female dogs. These results
      emphasize the role of the NO/cGMP pathway in the local vasodilatory response in
      female sexual organs and provide a rationale for testing PDE5 inhibitors, such as
      vardenafil, as a treatment for certain forms of female sexual dysfunction.

PMID- 12789395
TI  - Histological and functional aspects of different regions of the rabbit vagina.
AB  - Relatively little data is available on regional differences in both morphological
      and functional studies of vaginal smooth muscle in the rabbit. Histological and
      in vitro strip studies were performed upon the vaginal walls of 10-week-old New
      Zealand White rabbits discriminately according to location (upper, middle or
      lower) and the type of muscle arrangement (longitudinal or circular). The
      contraction and relaxation responses of the vaginal smooth muscle were assessed.
      The upper and middle third of the vagina were histologically characterized by an
      abundance of smooth muscle, while the lower third was composed of numerous
      sinusoids scattered among smooth muscle bundles. The peak amplitudes of 60 mM KCl
      induced contraction per tissue strip weight were regionally different
      (upper>middle>lower). Contractile responses induced by adrenergic agonists
      (epinephrine, norepinephrine, phenylephrine and isopreterenol) showed regional
      differences, and were mainly of a tonic nature in lower part and strong phasic in
      middle and upper vagina. Electrical field stimulation induced a prominent
      relaxation response in the lower third of the vagina precontracted with
      phenylephrine (5 microM). This relaxation response was partially inhibited by N
      omega-nitro-L-arginine methyl ester (NAME, 43.3+/-6.9%, s.e.), a nitric oxide
      synthase inhibitor, and D-vasoactive intestinal peptide (VIP) (11.3+/-4.4%), a
      VIP receptor antagonist. The type of muscle arrangement did not affect the
      results. Our results demonstrated that rabbit vagina has regional difference, not
      only histologically but also functionally. The contractile response was induced
      in all regions of the rabbit vagina by sympathetic agonists, while the prominent
      nerve-mediated relaxation was identified in the lower third portion of the rabbit
      vagina. The nature of relaxation and contractile function of vagina awaits future
      investigation.

PMID- 12789396
TI  - Infectious diseases and bioweapons. Science and political economics of affiction.

PMID- 12789397
TI  - The embodiment of inequality. AIDS as a social condition and the historical
      experience in South Africa.

PMID- 12789398
TI  - HIV and AIDS in relation to other pandemics. Among the viruses plaguing humans,
      HIV is a recent acquisition. Its outstanding success as an infection poses
      immense scientific challenges to human health and raises the question "What comes
      nest?".

PMID- 12789399
TI  - Gaps between the rich and the poor. The widening differences in wealth, life
      expectancy, public health infrastructure and perception of threats, and the
      consequences for global security.

PMID- 12789400
TI  - Infectious disease in Haiti. HIV/AIDS, tuberculosis and social inequalities.

PMID- 12789401
TI  - The economic divide and tuberculosis. Tuberculosis is not just a medical problem,
      but also a problem of social inequality and poverty.

PMID- 12789402
TI  - Malaria: past problems and future prospects. After more than a decade of neglect,
      malaria is finally black on the agenda for both biomedical research and public
      health politics.

PMID- 12789403
TI  - Plagues and peoples revisited. Basic and strategic research for ingectious
      disease control at the intergace in the life, health and social sciences.

PMID- 12789404
TI  - Neglected diseases: under-funded research and inadequate health interventions.
      Can we change this reality?

PMID- 12789405
TI  - The molecular biologist against infectious disease. Infectious diseases, in both
      the developing and the developed world, still pose considerable challenges to
      biomedical research. But science alone is clearly not sufficient to overcome the
      burden of disease in the world.

PMID- 12789406
TI  - Product R&D for neglected diseases. Twenty-seven years of WHO/TDR experiences
      with public-private partnerships.

PMID- 12789407
TI  - The history of biological warfare. Human experimentation, modern nightmares and
      lone madmen in the twentieth century.

PMID- 12789408
TI  - Advances in life sciences and bioterrorism. Risks, perspectives and
      responsibilities.

PMID- 12789409
TI  - Genetic engineering and biological weapons. New technologies, desires and threats
      from biological research.

PMID- 12789410
TI  - Strengthening the BTWC. The role of Biological and Toxin Weapons Convention in
      combating natural and deliberate disease outbreaks.

PMID- 12789411
TI  - Points of regulation for auxin action.
AB  - There have been few examples of the application of our growing knowledge of
      hormone action to crop improvement. In this review we discuss what is known about
      the critical points regulating auxin action. We examine auxin metabolism,
      transport, perception and signalling and identify genes and proteins that might
      be keys to regulation, particularly the rate-limiting steps in various pathways.
      Certain mutants show that substrate flow in biosynthesis can be limiting. To date
      there is little information available on the genes and proteins of catabolism.
      There have been several auxin transport proteins and some elegant transport
      physiology described recently, and the potential for using transport proteins to
      manage free indole-3-acetic acid (IAA) concentrations is discussed. Free IAA is
      very mobile, and so while it may be more practical to control auxin action
      through managing the receptor and signalling pathways, the candidate genes and
      proteins through which this can be done remain largely unknown. From the
      available evidence, it is clear that the reason for so few commercial
      applications arising from the control of auxin action is that knowledge is still
      limited.

PMID- 12789412
TI  - High-frequency somatic embryo production and maturation into normal plants in
      cotton (Gossypium hirsutum) through metabolic stress.
AB  - A highly efficient somatic embryo production and maturation procedure has been
      developed to regenerate plantlets from cotton ( Gossypium hirsutum). This
      procedure involves the acceleration of differentiation through manipulations of
      nutrient and microenvironment conditions. Embryogenic calli, initiated from
      hypocotyls or cotyledonary leaf sections on MS medium containing 0.1 mg/l 2,4
      dichlorophenoxyacetic acid, 0.5 mg/l kinetin, and 3% maltose produced globular
      stage somatic embryos when transferred to hormone-free MS medium supplemented
      with high concentrations of nitrate. Subculture of globular embryos on hormone
      free MS medium led to the development of torpedo- and cotyledonary-stage at a low
      frequency (two to four per plate) with the majority of embryos lacking further
      growth or entering into the dedifferentiation stage. Significant improvement in
      embryogenesis (two- to threefold) was achieved when calli were cultured on 1/5
      strength MS medium irrespective of stress treatment. However, the frequency of
      globular embryos developing into normal plantlets improved considerably (20-24
      per plate) when cultured on filter paper placed on MS medium. In this procedure,
      about 33% of globular embryos not only developed into the cotyledonary stage but
      rooted simultaneously, eliminating a separate rooting step. More than 70% of
      cotyledonary embryos developed into normal plantlets when cultured on full-
      strength MS medium containing 0.05 mg/l gibberellic acid.

PMID- 12789413
TI  - Adventitious shoot regeneration from in vitro cultured leaves of London plane
      tree (Platanus acerifolia Willd.).
AB  - Adventitious shoots were successfully regenerated from leaf explants of in vitro
      cultures of Platanus acerifolia Willd. The leaves of three clones (genotypes),
      designated as PH1, PH2 and PC, respectively, were wounded by three to four
      transverse cuts through the midvein and cultured on 26 media based on Murashige
      and Skoog (MS) basal medium, containing different concentrations of 6
      benzylaminopurine (BAP) in combination with different concentrations of indole-3
      butyric acid (IBA). The highest regeneration rate (>90%) and the largest number
      of shoot clumps per regenerating leaf (>4 shoot clumps/explant) were obtained
      with leaves of genotype PH2 cultured on MS basal medium supplemented with 17.76
      microM BAP and 4.92 microM IBA. The other two genotypes, PH1 and PC, showed very
      low capability of shoot regeneration (<10%) on all the media tested. Shoots on
      leaf explants originated mainly from callus that developed around the cut end of
      petioles and along the cuts across the midvein. The regenerated shoots were
      micropropagated, rooted and transplanted to the soil successfully.

PMID- 12789414
TI  - Enhanced bud and bulblet regeneration from bulbs of Nerine sarniensis cultured in
      vitro.
AB  - Nerine (Nerine sarniensis) cv. Salmon Supreme in vitro-grown bulblets, 7-9 mm in
      diameter, were cut in half longitudinally and used for adventitious bud
      initiation following dissection of the roots and two-thirds of the upper part of
      the bulblets. The terminal apex was injured with a hot, sterile microscope
      dissecting needle. The highest number of buds formed (seven to nine buds per
      halved bulblet) on a semi-solid Murashige and Skoog (MS) basal salts medium
      supplemented with 3% sucrose and either 1 microM 6-benzylaminopurine (BA) and 1
      microM alpha-naphthaleneacetic acid (NAA) or 0.5 microM BA and 0.1 microM NAA.
      Bulblet halves were cultured in the dark for 11-13 weeks with one subculture
      after 6 weeks. Anatomical studies indicated that the initiation of adventitious
      buds on the abaxial side of the inner scales of the halved bulblet was adjacent
      to the basal plate and started from the leaf primordium and a meristematic bulge.
      Buds developed directly into small bulblets after they were transferred to semi
      solid MS basal salts medium supplemented with 6% sucrose, 10 microM indole-3
      butyric acid (IBA) and 0.25% activated charcoal. Small bulblets cultured in
      liquid MS medium supplemented with additional KH(2)PO(4 )(170 mg l(-1)), 6%
      sucrose and 0.1 microM NAA under a 16/8-h (light/dark) photoperiod for 8 weeks
      grew into larger bulbs faster than those cultured on semi-solid medium. The bulbs
      were rooted on a semi-solid medium after 4 weeks and then transferred to the
      soil. As many as 18 bulblets developed and rooted from one in vitro-grown bulb
      after 25-27 weeks.

PMID- 12789415
TI  - Expression of hemagglutinin protein of Rinderpest virus in transgenic pigeon pea
      [Cajanus cajan (L.) Millsp.] plants.
AB  - Rinderpest virus is the causative agent of a devastating, often fatal disease in
      wild and domestic bovids that is endemic in Africa, the Middle East and South
      Asia. The existing live attenuated vaccine is heat-labile, and thus there is a
      need for the development of new strategies for vaccination. This paper reports
      the development of transgenic pigeon pea [ Cajanus cajun (L.) Millsp.] expressing
      one of the protective antigens, the hemagglutinin (H) protein of Rinderpest
      virus. A 2-kb fragment containing the coding region of the H protein was cloned
      into pBI121 and mobilized into Agrobacterium tumefaciensstrain EHA105. Embryonic
      axes and cotyledonary nodes from germinated seeds of pigeon pea were used for
      transformation. The presence of the transgene in transgenic plants was confirmed
      by Southern blots, and the specific transcription of the marker gene in the
      plants was demonstrated by reverse transcription-polymerase chain reaction.
      Integration of the H gene into the pigeon pea genome was confirmed by Southern
      hybridization. The expression of the H protein in the transgenic lines was
      confirmed by Western blot analysis using a polyclonal monospecific antibody to
      the H protein. The highest level of expression of the hemagglutinin protein in
      leaves of pigeon pea was 0.49% of the total soluble protein. The transgenic
      plants were fertile and the transgene expressed in the progeny.

PMID- 12789416
TI  - Factors influencing successful Agrobacterium-mediated genetic transformation of
      wheat.
AB  - The development of a robust Agrobacterium-mediated transformation protocol for a
      recalcitrant species like bread wheat requires the identification and
      optimisation of the factors affecting T-DNA delivery and plant regeneration. We
      have used immature embryos from range of wheat varieties and the Agrobacterium
      strain AGL1 harbouring the pGreen-based plasmid pAL156, which contains a T-DNA
      incorporating the bar gene and a modified uidA (beta-glucuronidase) gene, to
      investigate and optimise major T-DNA delivery and tissue culture variables.
      Factors that produced significant differences in T-DNA delivery and regeneration
      included embryo size, duration of pre-culture, inoculation and co-cultivation,
      and the presence of acetosyringone and Silwet-L77 in the media. We fully describe
      a protocol that allowed efficient T-DNA delivery and gave rise to 44
      morphologically normal, and fully fertile, stable transgenic plants in two wheat
      varieties. The transformation frequency ranged from 0.3% to 3.3%. Marker-gene
      expression and molecular analysis demonstrated that transgenes were integrated
      into the wheat genome and subsequently transmitted into progeny at Mendelian
      ratios.

PMID- 12789417
TI  - Agrobacterium tumefaciens-mediated transformation of Indian mulberry, Morus
      indica cv. K2: a time-phased screening strategy.
AB  - An efficient and reproducible protocol for the production of transgenic plants
      was developed for Morus indica cv. K2 by Agrobacterium tumefaciens-mediated
      transformation. The hypocotyls, cotyledon, leaf and leaf callus explants
      precultured for 5 days on regeneration medium were co-cultivated with a bacterial
      suspension at 10(9) cells/ml for 3 days in the dark. Infectivity of A.
      tumefaciens strain LBA4404 was more than that of strains GV2260 and A281, and
      among the various plasmids tried, pBI121 and pBI101:Act1 transformed nearly 100%
      of the explants followed closely by p35SGUSINT. About 90-100% of the explants
      tested positive in the beta-glucuronidase (GUS) histochemical assay performed
      after 3 days of co-cultivation. This high level of transient expression, however,
      decreased to 20-25% after 15 days. Gus activity was most stable in the callus
      explants, which emerged as the explant of choice for transformation. The
      transformed explants were selected on 50-75 mg/l kanamycin for 1 month, and 25
      50% of the explants developed adventitious buds. On the basis of kanamycin
      resistant shoots produced from the total number of explants inoculated, the
      transformation efficiency was 44%. After 1 month, 40% of these shoots displayed
      high gus activity as assessed by the GUS fluorometric assay. On a selection-free
      root induction medium, 80% of the shoots developed roots and 90% of the potted
      plantlets acclimatized to the growth room conditions. The 3-month-old regenerates
      showed gus and nptII(neomycin phosphotransferase II) gene activity as assayed by
      the GUS fluorometric assay and nptII enzyme assay, followed by PCR polymerase
      chain reaction (54.5%) analysis after 6-months. Transgene integration into the
      nuclear genome of 1-year-old regenerates was confirmed in 10 of the 18
      transformants tested by Southern analysis. The transformation efficiency as
      defined by the number of transgenic plants produced from the total number of
      explants co-cultivated was 6%.

PMID- 12789420
TI  - Ultrastructural changes associated with cryopreservation of banana ( Musa spp.)
      highly proliferating meristems.
AB  - Cryopreservation has been shown to improve the frequency of virus elimination -
      specifically cucumber mosaic virus and banana streak virus - from banana ( Musa
      spp.) plants. To understand the mode of action of cryopreservation for the
      eradication of viral particles, we examined the ultrastructure of meristem tips
      at each step of the cryopreservation process. Excised meristematic clumps
      produced from infected banana plants belonging to cv. Williams (AAA, Cavendish
      subgroup) were cryopreserved through vitrification using the PVS-2 solution. We
      demonstrated that the cryopreservation method used only allowed survival of small
      areas of cells in the meristematic dome and at the base of the primordia.
      Cellular and subcellular changes occurring during the cryopreservation process
      are discussed.

PMID- 12789418
TI  - Gene silencing in transgenic soybean plants transformed via particle bombardment.
AB  - Transgenes are susceptible to silencing in plants especially when multiple copies
      of the gene of interest are introduced. Transgenic plants derived by particle
      bombardment, which is the common method for transforming soybean, have a tendency
      to have multiple integration events. Three independent transgenic soybean plants
      obtained via particle bombardment were analyzed for transgene silencing. A GUS
      transgenic soybean line had at least 100 copies of the GUS gene while there were
      approximately 60 copies of the transgene in the two soybean lines transformed
      with a 15-kDa zein storage protein gene from maize. Soybean plants transformed
      with the GUS gene showed variable GUS expression. The coding region and promoter
      of the GUS gene in the plants with low expression of GUS were heavily methylated.
      Variability in GUS expression was observed in the progeny of the high expressors
      in the T(2) and T(3) generations as well. Expression level of the 15-kDa zein
      gene in transgenic soybean plants showed correlation with the level of transgene
      methylation. The helper component-proteinase from potyviruses is known to
      suppress post-transcriptional gene silencing. Transgenic plants were inoculated
      with the soybean mosaic potyvirus (SMV) to test possible effects on transgene
      silencing in soybean. Infection with SMV did not suppress transgene silencing in
      these plants and suggests that the silencing in these plants may not be due to
      post-transcriptional gene silencing.

PMID- 12789419
TI  - Globulin-1 gene expression in regenerable Zea mays (maize) callus.
AB  - Since maize callus cultures regenerate plants via somatic embryogenesis, one
      might expect to find similar proteins in both zygotic embryos and tissue
      cultures. The 63-kD globulin protein designated GLB1, the expression of which is
      regulated by abscisic acid (ABA), is one such protein. When maize Type I
      regenerable callus was exposed for 24 h to 0.1 m M ABA or a water stress induced
      by 0.53 M mannitol, GLB1 was produced as determined by Western analysis. This
      protein was not detected in ABA or mannitol-treated regenerable cultured tissue
      of a null genotype or in tissues not exposed to ABA or water stress. Exposure to
      ABA in the culture medium increased the callus ABA levels greatly but a mannitol
      induced water stress had only a small effect on ABA levels. Regenerable callus
      exposed to 0.1 m M ABA also produced mRNA that hybridized on a Northern blot with
      a globulin- 1 gene ( Glb1) probe. When both Type I and Type II regenerable
      cultured tissues were exposed to regeneration medium without ABA or mannitol,
      several GLB1 antibody immunoreactive proteins were produced. These proteins were
      not detected in regenerated plants nor in non-regenerable callus treated with
      ABA. These results suggest that: (1) at least for expression of Glb1, somatic
      embryogenesis is similar to zygotic embryogenesis, (2) there may be a regulatory
      role for auxin in the processing of Glb1-encoded polypeptides since fewer are
      seen when dicamba is present in the medium, (3) ABA has a role in somatic
      embryogenesis, and (4) regenerability of a maize callus culture may be assessed
      by treating the cultured tissue with 0.1 m M ABA to determine if GLB1 proteins
      are induced.

PMID- 12789421
TI  - Transient expression of Arabidopsis thaliana ascorbate peroxidase 3 in Nicotiana
      benthamiana plants infected with recombinant potato virus X.
AB  - We have explored the transient over-expression of Arabidopsis thaliana ascorbate
      peroxidase 3 (APX3) in Nicotiana benthamiana using a viral vector based on the
      potato virus X (PVX). Plants infected with a PVX:APX3 hybrid had a similar
      progression of viral particles compared to control plants infected with a PVX:GFP
      hybrid, indicating that infection was not affected by the over-expression of
      heterologous APX3. Our results also showed that in PVX:APX3-infected plants, the
      hybrid virus directed a high level of APX3 expression and the recombinant protein
      was functional, as inferred from the higher APX activity compared to mock and
      PVX:GFP hybrid-infected plants. The PVX recombinant expression system used is a
      simple and quick method for transient expression of heterologous APXs, which are
      expected to suffer specific processing in plant cells.

PMID- 12789423
TI  - Efficient callus formation and plant regeneration of goosegrass [Eleusine indica
      (L.) Gaertn.].
AB  - Efficient methods in totipotent callus formation, cell suspension culture
      establishment and whole-plant regeneration have been developed for the goosegrass
      [ Eleusine indica (L.) Gaertn.] and its dinitroaniline-resistant biotypes. The
      optimum medium for inducing morphogenic calli consisted of N6 basal salts and B5
      vitamins supplemented with 1-2 mg l(-1) 2,4-dichlorophenoxyacetic acid (2,4-D), 2
      mg l(-1) glycine, 100 mg l(-1) asparagine, 100 mg l(-1) casein hydrolysate, 30 g
      l(-1) sucrose and 0.6% agar, pH 5.7. The presence of organogenic and embryogenic
      structures in these calli was histologically documented. Cell suspension cultures
      derived from young calli were established in a liquid medium with the same
      composition. Morphogenic structures of direct shoots and somatic embryos were
      grown into rooted plantlets on medium containing MS basal salts, B5 vitamins, 1
      mg l(-1) kinetin (Kn) and 0.1 mg l(-1) indole-3-acetic acid (IAA), 3% sucrose,
      0.6% agar, pH 5.7. Calli derived from the R-biotype of E. indica possessed a high
      resistance to trifluralin (dinitroaniline herbicide) and cross-resistance to a
      structurally non-related herbicide, amiprophosmethyl (phosphorothioamidate
      herbicide), as did the original resistant plants. Embryogenic cell suspension
      culture was a better source of E. indica protoplasts than callus or mesophyll
      tissue. The enzyme solution containing 1.5% cellulase Onozuka R-10, 0.5%
      driselase, 1% pectolyase Y-23, 0.5% hemicellulase and N(6) mineral salts with an
      additional 0.2 M KCl and 0.1 M CaCl(2) (pH 5.4-5.5) was used for protoplast
      isolation. The purified protoplasts were cultivated in KM8p liquid medium
      supplemented with 2 mg l(-1) 2,4-D and 0.2 mg l(-1) Kn.

PMID- 12789424
TI  - Production of haploids from anther culture of banana [Musa balbisiana (BB)].
AB  - We report here, for the first time, the production of haploid plants of banana
      Musa balbisiana (BB). Callus was induced from anthers in which the majority of
      the microspores were at the uninucleate stage. The frequency of callus induction
      was 77%. Callus proliferation usually preceded embryo formation. About 8% of the
      anthers developed androgenic embryos. Of the 147 plantlets obtained, 41 were
      haploids (n=x=11). The frequency of haploid production depended on genotypes
      used: 18 haploid plants were produced from genotype Pisang klutuk, 12 from Pisang
      batu, seven from Pisang klutuk wulung and four from Tani. The frequency of
      regeneration was 1.1%, which was based on the total number of anthers cultured.
      Diploid plants (2n=2x=22) were also observed in the regenerated plants. The
      haploid banana plants that were developed will be important material for the
      improvement of banana through breeding programmes.

PMID- 12789425
TI  - An optimised protocol for plant regeneration from embryogenic suspension cultures
      of date palm, Phoenix dactylifera L., cv. Deglet Nour.
AB  - An improved protocol is described for the large-scale micropropagation of an
      elite date palm ( Phoenix dactylifera L.) cultivar, Deglet Nour. Clonal plants
      were regenerated from somatic embryos derived from highly proliferating
      suspension cultures. Friable embryogenic calli were initiated from both leaf and
      inflorescence explants. Suspension cultures consisting of pro-embryonic masses
      were established from calli showing a high competency for somatic embryogenesis.
      The subculture of suspensions in liquid medium enriched with low amounts of plant
      growth regulators (1 mg l(-1) 2,4-dichlorophenoxyacetic acid with 300 mg l(-1)
      charcoal) resulted in the differentiation of large numbers of somatic embryos.
      The productivity of the cultures increased 20-fold (from 10 to 200 embryos per
      month per 100 mg fresh weight of embryogenic callus) when embryogenic suspensions
      were used instead of standard cultures on solid media. The overall production of
      somatic embryos reached 10,000 units per litre per month. Partial desiccation of
      the mature somatic embryos, corresponding to a decrease in water content from 90%
      to 75%, significantly improved germination rates (from 25% to 80%). The cutting
      back of the cotyledonary leaf was also found to stimulate embryo germination.
      Flow cytometric analysis showed that the micropropagation protocol followed here
      did not affect the ploidy level of somatic embryo-derived plantlets.

PMID- 12789426
TI  - Regeneration of the Egyptian medicinal plant Artemisia judaica L.
AB  - An in vitro propagation system for Artemisia judaica L., a traditional Egyptian
      medicinal plant, has been developed. De novo shoot organogenesis was induced by
      culturing etiolated hypocotyls and intact seedlings on medium supplemented with
      thidiazuron [N-phenyl-N'-(1,2,3-thidiazol-yl) urea] via callusing at the
      cotyledonary notch region. Up to 16 shoots formed per seedling cultured on a
      medium containing 1 micro mol l(-1) thidiazuron for an optimal duration of
      exposure of 20 days. Regenerated shoots formed roots when subcultured onto a
      medium containing 1 micromol l(-1) indole-3-butyric acid. The regeneration
      protocol developed in this study provides a basis for germplasm conservation and
      for further investigation of medicinally active constituents of A. judaica.

PMID- 12789427
TI  - Production of haploids of neem (Azadirachta indica A. Juss.) by anther culture.
AB  - Androgenic haploids of the neem tree (Azadirachta indica A. Juss.) were produced
      by anther culture at the early- to late-uninucleate stage of pollen. Haploid
      formation occurred via callusing. The best medium for inducing callusing in the
      anther cultures was Murashige and Skoog's basal medium (MS) (9% sucrose)
      supplemented with 1 microM 2,4-D, 1 microM NAA and 5 microM BAP, while anther
      callus multiplied best on MS medium supplemented with 1 microM 2,4-D and 10
      microM Kn. These calli differentiated shoots when transferred to a medium
      containing BAP; 5 microM BAP was optimum for young calli (75% cultures
      differentiated shoots), but older calli showed the best regeneration with 7.5
      microM BAP. Shoots elongated at a lower concentration of BAP-0.5 microM. These
      shoots were multiplied by forced axillary branching and rooted in vitro. The
      plants were subsequently established in soil. Of the plants that regenerated from
      anther callus 60% were haploid, 20% were diploid and 20% were aneuploid.

PMID- 12789429
TI  - Agrobacterium tumefaciens-mediated transformation of eggplant (Solanum melongena
      L.) using root explants.
AB  - An efficient variety-independent method for producing transgenic eggplant
      (Solanum melongena L.) via Agrobacterium tumefaciens-mediated genetic
      transformation was developed. Root explants were transformed by co-cultivation
      with Agrobacterium tumefaciens strain LBA4404 harbouring a binary vector pBAL2
      carrying the reporter gene beta-glucuronidase intron (GUS-INT) and the marker
      gene neomycin phosphotransferase (NPTII). Transgenic calli were induced in media
      containing 0.1 mg l(-1) thidiazuron (TDZ), 3.0 mg l(-1) N(6)-benzylaminopurine,
      100 mg l(-1) kanamycin and 500 mg l(-1) cefotaxime. The putative transgenic shoot
      buds elongated on basal selection medium and rooted efficiently on Soilrite
      irrigated with water containing 100 mg l(-1) kanamycin sulphate. Transgenic
      plants were raised in pots and seeds subsequently collected from mature fruits.
      Histochemical GUS assay and polymerase chain reaction analysis of field
      established transgenic plants and their offsprings confirmed the presence of the
      GUS and NPTII genes, respectively. Integration of T-DNA into the genome of
      putative transgenics was further confirmed by Southern blot analysis. Progeny
      analysis of these plants showed a pattern of classical Mendelian inheritance for
      both the NPTII and GUS genes.

PMID- 12789428
TI  - Developing a scale-up system for the micropropagation of cucumber (Cucumis
      sativus L.): the effect of growth retardants, liquid culture and vessel size.
AB  - We investigated the effect of the growth retardant flurprimidol, the phase of the
      culture medium (solid versus liquid) and the size of the liquid culture vessel
      (250-ml flask versus 2.5-l airlift bioreactor) on the micropropagation of
      cucumber (Cucumis sativus L.) from nodal explants. Flurprimidol at concentrations
      of 0.1-2 mg l(-1) caused considerable growth retardation but increased, albeit
      slightly, the number of branches and buds and stimulated (solid medium) or
      reduced (liquid medium) the accumulation of NO(3)-and PO(4)(3-). Flurprimidol had
      varying effects on the accumulation of soluble sugars and antioxidant compounds.
      Bioreactor-derived plants showed an increased fresh weight and size but a
      decreased content of macronutrients, solid sugars, ascorbic acid and free
      antioxidant phenolics. The majority (95%) of the plants were successfully
      acclimatized after being graft on squash. The perspective for an efficient,
      commercial-level use of bioreactors in combination with growth retardants of this
      commercially important vegetable species is discussed.

PMID- 12789430
TI  - Additional virulence genes and sonication enhance Agrobacterium tumefaciens
      mediated loblolly pine transformation.
AB  - Additional virulence (vir) genes in Agrobacterium tumefaciens and sonication were
      investigated for their impact on transformation efficiency in loblolly pine
      (Pinus taeda L.). Mature zygotic embryos of loblolly pine were co-cultivated with
      disarmed A. tumefaciens strain EHA105 containing either plasmid vector
      pCAMBIA1301 or vector pCAMBIA1301 with an additional 15.8-kb fragment carrying
      extra copies of the Vir B, Vir C, and Vir G regions from the supervirulent
      plasmid pTOK47. pCAMBIA1301 contains hygromycin resistance and the beta
      glucuronidase (GUS) reporter gene. Expression of GUS was observed after 3-6 days
      of co-cultivation, with peak expression at approximately 21 days. The highest
      numbers of GUS-expressing areas were visible up to 21 days after co-cultivation,
      declining rapidly thereafter. Both transient and stable transformation
      efficiencies increased when the explants were sonicated before co-cultivation
      and/or the additional virB, virC, and virG genes were included with the
      pCAMBIA1301 plasmid T-DNA. Use of the plasmid with additional vir genes and
      sonication dramatically enhanced the efficiency of Agrobacterium-mediated gene
      transfer not only in transient expression but also in the recovery of hygromycin
      resistant lines. Stably transformed cultures and transgenic plants were produced
      from embryos transformed with A. tumefaciens EHA105 carrying pCAMBIA1301 or
      pCAMBIA1301+pTOK47 in the three families of loblolly pine. The presence of the
      introduced GUS and hygromycin phosphotransferase genes in the transgenic plants
      was confirmed by polymerase chain reaction and Southern hybridization analyses.

PMID- 12789431
TI  - Production of herbicide-resistant transgenic Panax ginseng through the
      introduction of the phosphinothricin acetyl transferase gene and successful soil
      transfer.
AB  - Herbicide-resistant transgenic Panax ginseng plants were produced by introducing
      the phosphinothricin acetyl transferase (PAT) gene that confers resistance to the
      herbicide Basta (bialaphos) through Agrobacterium tumefaciens co-cultivation.
      Embryogenic callus gathered from cotyledon explants of P. ginseng were pre
      treated with 0.5 M sucrose or 0.05 M MgSO(4 )before Agrobacterium infection. This
      pre-treatment process markedly enhanced the transient expression of the beta
      glucuronidase (GUS) gene. Embryogenic callus was initially cultured on MS medium
      supplemented with 400 mg/l cefotaxime for 3 weeks and subsequently subcultured
      five times to a medium containing 25 mg/l kanamycin and 300 mg/l cefotaxime.
      Somatic embryos formed on the surfaces of kanamycin-resistant callus. Upon
      development into the cotyledonary stage, these somatic embryos were transferred
      to a medium containing 50 mg/l kanamycin and 5 mg/l gibberellic acid to induce
      germination and strong selection. Integration of the transgene into the plants
      was confirmed by polymerase chain reaction and Southern analyses. Transfer of the
      transgenic ginseng plantlets to soil was successfully accomplished via
      acclimatization in autoclaved perlite. Not all of the plantlets survived in soil
      that had not been autoclaved because of fungal infection, particularly in the
      region between the roots and leaves. Transgenic plants growing in soil were
      observed to be strongly resistant to Basta application.

PMID- 12789432
TI  - Characterisation of the expression of a novel constitutive maize promoter in
      transgenic wheat and maize.
AB  - A novel constitutive promoter from the maize histone H2Bgene was recently
      identified. In this study, we characterised H2B promoter activity in both wheat
      and maize tissues using the gusA reporter gene and two synthetic versions of the
      pat (phosphinothricin acetyl transferase) selectable marker gene, namely mopat
      and popat. Analyses of transgenic plants showed that the H2B promoter is able to
      drive the expression of gusA to strong, constitutive levels in wheat and maize
      tissues. Using an H2B:mopat construct and phosphinothricin selection, we
      recovered transgenic wheat plants at efficiencies ranging from 0.3% to 7.4% (mean
      1.6%), and the efficiency of selection ranged from 40% to 100% (mean 77.7%). In
      another application, H2B was combined with the maize Ubi-1 or the maize Adh-1
      intron to drive the expression of mopat and popat. Transformation efficiencies
      with the Ubi-1 intron were between 1.4- to 16-fold greater than with the Adh-1
      intron. However, the use of either of the introns was necessary for the recovery
      of transgenic plants. Mopat gave higher transformation efficiencies and induced
      higher levels of PAT protein in maize tissues than popat.

PMID- 12789433
TI  - Somatic hybrids Solanum nigrum (+) S. tuberosum: morphological assessment and
      verification of hybridity.
AB  - Somatic hybrids between the cultivated potato diploid hybrid clone, ZEL-1136, and
      hexaploid non-tuber-bearing wild species Solanum nigrum L. exhibiting resistance
      to Phytophthora infestans were regenerated after PEG-mediated fusion of mesophyll
      protoplasts. The objective was to transfer the late-blight resistance genes from
      the wild species into plants of the cultivated potato clone. From a total of 59
      regenerants, 40 clones survived and have been maintained in vitro on hormone-free
      MS/2 medium. Thirty-two somatic hybrids were identified by their intermediate
      morphology (leaves of nigrum type and flowers of tuberosum type) and verified by
      flow cytometry and random amplified polymorphic DNA (RAPD) patterns. The RAPD
      analysis of nuclear DNA confirmed the hybrid nature of 29 clones. Flow cytometry
      revealed a wide range of ploidy in the generated hybrids, from nearly the tetra-
      to decaploid level. Most of the hybrid clones were stable in vitro, grew
      vigorously in soil, and set flowers and parthenocarpic berries. However, all of
      the flowering hybrids were male-sterile. Nine hybrid clones produced tuber-like
      structures in soil. The most vigorous flowering somatic hybrids were selected for
      assessment of the late-blight resistance.

PMID- 12789434
TI  - Gametic embryos of maize as a target for biolistic transformation: comparison to
      immature zygotic embryos.
AB  - The aim of the present study was to determine the suitability of maize gametic
      embryos of three ETH genotypes as a target for biolistic transformation. We
      studied parameters considered essential for a successful transformation, such as
      the frequency of secondary embryo formation, their regeneration ability and the
      transient transgene expression. Transformable zygotic embryos of one of the ETH
      genotypes were used as positive control. Our results indicate that gametic
      embryos can potentially be transformed by particle bombardment, since they
      responded positively to all the studied parameters, although with lower
      efficiencies than the zygotic embryos. In particular, differences were found in
      the rate of secondary embryogenesis and the density of transformed cells.

PMID- 12789435
TI  - Genetic transformation of two species of orchid by biolistic bombardment.
AB  - We report here the transformation of two species of orchid, Dendrobium
      phalaenopsis and D. nobile,by biolistic bombardment. Calli or protocorm-like
      bodies (PLBs) were used as target explants. Gold particles (1.0 microm) coated
      with plasmid DNA (pCAMBIA1301) encoding an intron-containing beta-glucuronidase
      gene (gus-int) and a hygromycin phosphotransferase (hpt) gene were introduced
      into the PLBs or calli using the Bio-Rad PDS-1000/He Biolistic Particle Delivery
      System. Calli and PLBs were then chopped up and pre-cultured in 1/2-strength MS
      medium supplemented with 0.4 M mannitol for a 1-h osmoticum treatment before
      bombardment. Immediately after bombardment, the calli and PLBs were transferred
      to 1/2-strength MS medium without mannitol for recovery. Putatively transformed
      plantlets were obtained by selection and regeneration on medium supplemented with
      30 mg/l hygromycin. The highest efficiency of transformation was obtained when
      selection was conducted at 2 days post-bombardment. For D. phalaenopsis and D.
      nobile, respectively, about 12% and 2% of the bombarded calli or PLBs produced
      independent transgenic plants. Integration and expression of the transgenes were
      confirmed by Southern hybridization and Northern hybridization. No nontransformed
      plants were regenerated, indicating a tight selection scheme. However, separate
      incorporation of the gus gene and the hpt gene was observed, and in one
      transgenic line the gus gene was integrated into the genome of the transgenic
      plant, but not expressed.

PMID- 12789436
TI  - Increased Agrobacterium-mediated transformation and rooting efficiencies in
      canola (Brassica napus L.) from hypocotyl segment explants.
AB  - An efficient protocol for the production of transgenic Brassica napus cv. Westar
      plants was developed by optimizing two important parameters: preconditioning time
      and co-cultivation time. Agrobacterium tumefaciens-mediated transformation was
      performed using hypocotyls as explant tissue. Two variants of a green fluorescent
      protein (GFP)-encoding gene--mGFP5-ER and eGFP--both under the constitutive
      expression of the cauliflower mosaic virus 35S promoter, were used for the
      experiments. Optimizing the preconditioning time to 72 h and co-cultivation time
      with Agrobacterium to 48 h provided the increase in the transformation efficiency
      from a baseline of 4% to 25%. With mGFP5-ER, the transformation rate was 17% and
      with eGFP it was 25%. Transgenic shoots were selected on 200 mg/l kanamycin.
      Rooting efficiency was 100% on half-strength Murashige and Skoog medium with 10
      g/l sucrose and 0.5 mg/l indole butyric acid in the presence of kanamycin.

PMID- 12789437
TI  - Visualization of somatic deletions mediated by R/RS site-specific recombination
      and induction of germinal deletions caused by callus differentiation and
      regeneration in rice.
AB  - A transgenic rice plant expressing the recombinase of Zygosaccharomyces rouxii
      under the control of the CaMV 35S promoter was crossed with a transgenic plant
      carrying a cryptic (beta-glucuronidase) GUS reporter gene, which was activated by
      recombinase-mediated deletions between two specific recombination sites ( RSs).
      In F(1) plants, GUS activity was observed as blue spots and stripes in vascular
      bundles in several parts of the leaves. GUS expression was detected in all of the
      calli induced from F(1) seeds and throughout the regenerated plants. DNA analysis
      using the polymerase chain reaction and Southern blotting showed that R/ RS
      mediated deletions occurred in all of the cells of the regenerated plants. Stable
      GUS expression was confirmed in the progeny resulting from self-pollination.
      Thus, the deletions obtained in the regenerated plants were genetically
      equivalent to the germinal deletions. These results indicate that the induction
      of callus differentiation and shoot regeneration is an effective manner to
      activate the R/ RS system and to produce plants with chromosomal deletions.

PMID- 12789439
TI  - An improved MUG fluorescent assay for the determination of GUS activity within
      transgenic tissue of woody plants.
AB  - Despite the success of the MUG fluorometric assay for quantitative analysis of
      beta-glucuronidase (GUS) activity within a vast array of transgenic plant species
      and tissues, attempts to apply this protocol for analysis of woody plants has
      been found to be problematic, primarily due to the interfering effects of
      phenolics and other secondary metabolites. Our analysis of transgenic spruce
      needles and poplar leaves illustrates that low tissue mass to extract volume,
      along with the inclusion of polyvinylpolypyrolidone and either beta
      mercaptoethanol or metabisulphite, are essential for producing reliable results.
      The primary action of these additives was found to involve increased GUS
      extractability and the preservation of GUS activity during extract manipulation,
      but they were not completely effective in eliminating GUS enzymatic inhibitors.
      Normalization of GUS activity upon DNA concentration was also found to be an
      effective alternative to protein concentration, providing the ability to make
      cross-species and inter-tissue comparisons of gusA transgene activity.

PMID- 12789438
TI  - Light-regulated differential expression of pea chloroplast and cytosolic fructose
      1,6-bisphosphatases.
AB  - The light-regulated differential expression of pea chloroplast and cytosolic
      fructose-1,6-bisphosphatases (FBPase) was investigated using enzyme activity
      assay, immunoblot, and Northern blot analyses. The enzyme activities of both
      chloroplast and cytosolic FBPases gradually increased under continuous white
      light illumination, although the increase in chloroplast FBPase was more drastic.
      Northern and immunoblot analyses also indicated that light stimulated the
      expression of both enzymes. Enzyme activity and the transcript levels of both
      enzymes gradually decreased under the dark treatment, although protein levels
      were unchanged for up to 24 h following the initiation of culture in the dark,
      indicating that reversible modifications of the enzymes may occur during the
      transition from light to dark (or the reverse). Light pulse experiments using
      blue (420 nm) and red/far-red (660/730 nm) light were carried out to analyze the
      photoreceptors related to the light-mediated expression of both enzymes.
      Expression of the chloroplast enzyme was very sensitive to red or far-red light
      pulses-it was induced by red light, but suppressed by far-red light pulses, as
      determined by enzyme activity, immunoblot, and Northern blot analyses, suggesting
      that red light signaling is involved in the control of chloroplast FBPase
      expression. However, cytosolic FBPase was virtually insensitive to blue or
      red/far-red light pulses in terms of enzyme activity, as determined by protein
      and transcript levels, indicating that cytosolic enzyme expression is not
      directly regulated by light signals. Instead, the expression of the cytosolic
      enzyme may be closely related to photosynthetic energy conversion accompanied by
      continuous white light irradiation.

PMID- 12789440
TI  - Adventitious shoot regeneration from seven commercial strawberry cultivars
      (Fragaria x ananassa Duch.) using a range of explant types.
AB  - The parameters for optimal regeneration of seven commercial strawberry cultivars
      were tested using a range of explants and culture conditions. Efficient levels of
      regeneration--those needed to carry out transformation experiments--with the
      cultivars Calypso, Pegasus, Bolero, Tango and Emily were achieved with leaf
      discs, petioles, roots and stipules. Regeneration from cv. Elsanta proved to be
      difficult from all explant material, although unpollinated ovaries proved to be a
      promising explant source, with 12% of the explants regenerating shoots. In cv.
      Eros, regeneration occurred only from root tissue. A comparison of the genetic
      background suggests that there is a strong genetic component amongst the
      different cultivars determining their regeneration capacity. The development of
      these regeneration systems provides a means to use almost the whole stock plant
      for the efficient genetic transformation of commercial strawberry varieties.

PMID- 12789441
TI  - A xyloglucan from seeds of the native Brazilian species Hymenaea courbaril for
      micropropagation of Marubakaido and Jonagored apples.
AB  - Xyloglucan was extracted from seeds of Hymenaea courbaril and mixed with agar to
      prepare a solid culture medium used for micropropagation of the Marubakaido apple
      rootstock (Malus prunifolia Borkh) and cv. Jonagored (Malus domestica). The
      performance on gels created from a blend of 0.4%agar and 0.2% xyloglucan (w/v)
      was compared with that on media gelled with a standard concentration 0.6% (w/v)
      of agar. The growth of shoots and the multiplication rate were higher on the
      modified culture medium than on the agar-gelled medium. The occurrence of
      hyperhydric shoots was lower on the modified medium. In the absence of auxin,
      shoot rooting reached 70% (Marubakaido) and 66% (Jonagored) on the agar
      xyloglucan medium and 6.7% and 10.4%, respectively, on the agar medium. When 0.25
      microM indole-3-butyric acid (IBA) was added to both media, the modified medium
      gave better results in terms of rooting percentage and quality of roots than the
      agar-gelled medium.

PMID- 12789442
TI  - Thidiazuron induces shoot organogenesis at low concentrations and somatic
      embryogenesis at high concentrations on leaf and petiole explants of African
      violet (Saintpaulia ionantha Wendl).
AB  - Regeneration via shoot organogenesis and somatic embryogenesis was observed from
      thidiazuron (TDZ)-treated leaf and petiole explants of greenhouse- and in vitro
      grown African violet plants. The response of cultures to other growth regulators
      over a range of 0.5 microM to 10 microM was 50% less than that observed with TDZ.
      A comparative study among several cultivars of African violet indicated that
      "Benjamin" and "William" had the highest regeneration potential. In "Benjamin",
      higher frequencies of shoot organogenesis (twofold) and somatic embryogenesis (a
      50% increase) were observed from in vitro- and greenhouse-grown plants,
      respectively. At concentrations lower than 2.5 microM, TDZ induced shoot
      organogenesis, whereas at higher doses (5-10 microM) somatic embryos were formed.
      These findings provide the first report of simultaneous shoot organogenesis and
      somatic embryogenesis of African violet explants in response to TDZ.

PMID- 12789443
TI  - Rapid in vitro multiplication and ex vitro rooting of Rotula aquatica Lour., a
      rare rhoeophytic woody medicinal plant.
AB  - Single medium-based efficient protocols for large-scale multiplication of the
      rare woody aromatic medicinal plant Rotula aquatica Lour. by means of axillary
      bud multiplication and indirect organogenesis were established using Murashige
      and Skoog (MS) medium. There were no significant differences with respect to the
      induction of shoots per node or callus and roots per shoot on media prepared
      either with tap water and commercial sugar or those prepared with double
      distilled water and tissue culture-grade sucrose. The most effective medium for
      axillary bud proliferation was MS medium fortified with 1.0 mg l(-1 )N(6)
      benzylaminopurine (BAP) and 0.5 mg l(-1 )indole-3-butyric acid (IBA), on which
      shoots were induced at the rate of 15 per node. The excision of node segments
      from the in vitro-derived shoots and their subsequent culture on medium
      supplemented with same concentrations of BAP and IBA facilitated enhanced
      axillary bud proliferation. Callus that developed from the lower cut end of the
      node explants induced shoots during subculture on half-strength MS medium with
      1.0 mg l(-1 )BAP and 0.5 mg l(-1 )kinetin. The shoots developed rooted best on
      half-strength MS medium supplemented with 0.5 mg l(-1 )naphthaleneacetic acid
      (NAA). Rooted shoots, following acclimation in the greenhouse, were successfully
      transferred to field conditions, and 80% of the plantlets survived. When the
      basal ends of shoots harvested from multiplication medium were dipped in an NAA
      (0.5 mg l(-1)) solution for 25 days, a mean of 5.6 roots per shoot developed; the
      transfer to small pots facilitated the survival of 75% of the rooted shoots. Ex
      vitro rooting by direct transfer of the shoots from the multiplication medium to
      the greenhouse resulted in a 65% survival. Commercial sugar and tap water and ex
      vitro rooting make the protocol economically advantageous. About 750 plantlets
      were procured in a 3-month period starting from a single node explant.

PMID- 12789444
TI  - Characterization of grapefruit plants (Citrus paradisi Macf.) transformed with
      citrus tristeza closterovirus genes.
AB  - Grapefruit (Citrus paradisi Macf. cv Duncan) plants were transformed with several
      sequences from citrus tristeza closterovirus (CTV) that varied in terms of
      position in the CTV genome and virus strain origin in an attempt to obtain
      resistant plants. The sequences included the capsid protein gene from three
      different strains, a nontranslatable version of the capsid protein gene, the
      replicase (RdRp), the minor capsid protein (p27), a highly transcribed gene of
      unknown function (p20) and the more conserved 3' end of the genomic RNA.
      Transgenic plants were generated from all of the constructs, except from the p20
      and p27 genes. Southern and Western blot analyses demonstrated that stably
      transformed grapefruit plants were obtained and that at least some transgenes
      were expressed. In a first effort at virus challenge, 25 transgenic lines were
      graft inoculated with a severe strain of CTV. Although some transgenic plants
      averaged lower titers of virus than controls, there was great variability in
      titer in both controls and transgenic plants, and all were apparently susceptible
      to the virus.

PMID- 12789445
TI  - Agrobacterium tumefaciens-mediated transformation of wheat using a superbinary
      vector and a polyamine-supplemented regeneration medium.
AB  - Immature embryo-derived calli of spring wheat (Triticum aestivum L.) cv Veery5
      were transformed using Agrobacterium tumefaciens strain LBA4404 carrying either
      binary vector pHK22 or superbinary vector pHK21, the latter carrying an extra set
      of vir genes--vir B, -C and -G. In both cases, transient beta-glucuronidase (
      GUS) expression ranging from 35-63% was observed 3 days after co-cultivation, but
      587 calli infected with pHK22/LBA4404 failed to produce a single stably
      transformed plant, whereas 658 calli infected with pHK21/LBA4404 gave rise to 17
      transformants carrying both the GUS and bar genes. Regeneration media
      supplemented with 0.1 M spermidine improved the recovery of transformants from
      pHK21/LBA4404-infected calli from 7% to 24.2%, resulting in an increase in the
      overall transformation frequency from 1.2% to 3.9%. The results suggest that two
      important factors that could lead to an improvement in transformation frequencies
      of cereals like wheat are (1) the use of superbinary vectors and (2) modification
      of the polyamine ratio in the regeneration medium. Stable expression and
      inheritance of the transgenes was confirmed by both genetic and molecular
      analyses. T1 progeny showed segregation of the transgenes in a typical Mendelian
      fashion in most of the plants. Of the transformed plants, 35% showed single-copy
      insertion of the transgene as shown by both Southern analysis and the segregation
      ratios.

PMID- 12789446
TI  - Agrobacterium tumefaciens-mediated transformation of Festuca arundinacea
      (Schreb.) and Lolium multiflorum (Lam.).
AB  - Agrobacterium tumefaciens strain LBA4404 carrying plasmid pTOK233 encoding the
      hygromycin resistance (hph) and beta-glucuronidase (uidA) genes has been used to
      transform two agronomic grass species: tall fescue (Festuca arundinacea) and
      Italian ryegrass (Lolium multiflorum). Embryogenic cell suspension colonies or
      young embryogenic calli were co-cultured with Agrobacterium in the presence of
      acetosyringone. Colonies were grown under hygromycin selection with cefotaxime
      and surviving colonies plated on embryogenesis media. Eight Lolium (six
      independent lines) and two Festuca plants (independent lines) were regenerated
      and established in soil. All plants were hygromycin-resistant, but histochemical
      determination of GUS activity showed that only one Festuca plant and one Lolium
      plant expressed GUS. Three GUS-negative transgenic L. multiflorum and the two F.
      arundinacea plants were vernalised and allowed to flower. All three Lolium plants
      were male- and female-fertile, but the Festuca plants failed to produce seed.
      Progeny analysis of L. multiflorum showed a 24-68% inheritance of the hph and
      uidA genes in the three lines with no significant difference between paternal and
      maternal gene transmission. However, significant differences were noted between
      the paternal and maternal expression of hygromycin resistance.

PMID- 12789447
TI  - Molecular characterization of cytoplasmic and nuclear genomes in phenotypically
      abnormal Valencia orange (Citrus sinensis) + Meiwa kumquat (Fortunella
      crassifolia) intergeneric somatic hybrids.
AB  - Organelle DNA inheritance of four 10-year-old somatic hybrid trees between
      Valencia orange [Citrus sinensis (L.) Osbeck] and Meiwa kumquat (Fortunella
      crassifolia Swingle) was analyzed by cleaved amplified polymorphic sequence
      (CAPS) and restriction fragment length polymorphisms (RFLPs). Five chloroplast
      (cp) and three mitochondrial (mt) universal primer pairs were amplified, but no
      polymorphisms were detected. When the polymerase chain reaction products were
      digested by 15 restriction enzymes, four polymorphic cpDNA-CAPS and two mtDNA
      CAPS markers were found. Both the cpDNA and mtDNA in the somatic hybrids were
      derived from Valencia orange (the embryogenic suspension parent). Genomic DNA of
      the somatic hybrids and corresponding parents was digested by five restriction
      endonucleases and hybridized with one chloroplast probe (RbcL- RbcL) and nine
      mitochondrial probes (coxI, coxII, c oxIII, c ob, atpA, tyr, proI, atp6 and
      atp9). The results indicated that three hybrid plants shared one strong cpDNA
      band with both parents and that the remaining one plant had two additional novel
      bands besides the shared band, while their mtDNA was identical to that of
      Valencia orange plus non-parental bands. When data on the mtDNA banding patterns
      were combined with observations on phenotypic performance in the field, it was
      found that the more complex mtDNA banding pattern coincided with increased vigor
      of the plant. The stability of the organelle genomes was studied by extracting
      the genomic DNA of one hybrid plant at monthly intervals for 1 year and then
      analyzing it using RFLPs. Before the dieback of the shoots, two fragments of the
      mtDNA were lost while the cpDNAs remained stable. Ploidy analysis by flow
      cytometry showed that all of the hybrids were stable tetraploids. Four simple
      sequence repeat primer pairs were applied to detect microsatellite alleles of the
      four hybrid plants, both parents and the 12 DNA samples from one plant. The
      results showed that all hybrids had biparental bands uniformly, which indicated
      that they had the same nuclear background. These results suggest that the mtDNA
      pattern is correlated with the phenotypic abnormality of Valencia and kumquat
      somatic hybrid plants and that nuclear-cytoplasm incompatibility may be the cause
      of dieback.

PMID- 12789448
TI  - Evaluation of different promoters driving the GFP reporter gene and selected
      target tissues for particle bombardment of Dendrobium Sonia 17.
AB  - Three different morphological callus types, identified as type A, B and C, and
      tips of in vitro inflorescences were used as target tissues for genetic
      transformation. Five different DNA plasmids carrying a synthetic green
      fluorescent protein (gfp) gene driven by different promoters, CaMV 35S, HBT, and
      Ubi1 were tested for the genetic transformation of Dendrobium Sonia 17. 35S-sgfp
      TYG-nos (p35S) with the CaMV 35S promoter showed the highest GFP transient
      expression rate, while the HBT and Ubi1 promoters showed a relatively lower
      expression rate in all of the target tissues tested. The highest number of GFP
      expressing cells was observed on day 2 post-bombardment, and the number declined
      gradually over the course of the next 2 weeks. Type A and B callus were found to
      be the best potential target tissues for genetic transformation.

PMID- 12789449
TI  - Regeneration of transformed verbena (Verbena x hybrida) by Agrobacterium
      tumefaciens.
AB  - Verbena (Verbena x hybrida), an important floricultural species, was successfully
      regenerated from stem segments on Murashige and Skoog's basal medium supplemented
      with thidiazuron and indole-3-acetic acid. A transformation system was developed
      using cvs. Temari Scarlet, Temari Sakura, Tapien Rose and TP-P2. Agrobacterium
      tumefaciens strain Agl0 harboring the sGFP gene was infected into stem segments.
      Transformation efficiency was improved by evaluating and manipulating the age of
      the plant material, the concentration of kanamycin in the medium during
      selection, and the length of the culture period in the dark. After 2-3 months of
      culture on the selection medium, GFP-positive shoots were obtained in all four of
      the cultivars tested. These shoots were successfully acclimated and set flowers
      within 2-3 months in a greenhouse. GFP was expressed in all of the organs
      including the floral parts. Stable genomic transformation was confirmed by
      Southern blot analysis. No morphological differences were observed between the
      transformed plants and their host plants.

PMID- 12789450
TI  - Expression of green fluorescent protein and its inheritance in transgenic oat
      plants generated from shoot meristematic cultures.
AB  - The expression of green fluorescent protein (GFP) and its inheritance were
      studied in transgenic oat ( Avena sativa L.) plants transformed with a synthetic
      green fluorescent protein gene [sgfp(S65T)] driven by a rice actin promoter. In
      vitro shoot meristematic cultures (SMCs) induced from shoot apices of germinating
      mature seeds of a commercial oat cultivar, Garry, were used as a transformation
      target. Proliferating SMCs were bombarded with a mixture of plasmids containing
      the sgfp(S65T) gene and one of three selectable marker genes, phosphinothricin
      acetyltransferase (bar), hygromycin phosphotransferase (hpt) and neomycin
      phosphotransferase (nptII). Cultures were selected with bialaphos, hygromycin B
      and geneticin (G418), respectively, to identify transgenic tissues. From 289
      individual explants bombarded with the sgfp(S65T) gene and one of the three
      selectable marker genes, 23 independent transgenic events were obtained, giving a
      8.0% transformation frequency. All 23 transgenic events were regenerable, and 64%
      produced fertile plants. Strong GFP expression driven by the rice actin promoter
      was observed in a variety of tissues of the T(0) plants and their progeny in 13
      out of 23 independent transgenic lines. Stable GFP expression was observed in
      T(2) progeny from five independent GFP-expressing lines tested, and homozygous
      plants from two lines were obtained. Transgene silencing was observed in T(0)
      plants and their progeny of some transgenic lines.

PMID- 12789451
TI  - Improved Agrobacterium-mediated transformation of sunflower (Helianthus annuus
      L.): assessment of macerating enzymes and sonication.
AB  - Agrobacterium -mediated transformation of shoot apices of sunflower (Helianthus
      annuus L.) was evaluated following wounding by cell-wall-digesting enzymes and
      sonication. The frequency of explants with regenerated shoots expressing GUS
      (beta-glucuronidase) or GFP (green fluorescent protein) increased following
      treatment with the macerating enzymes cellulase Onozuka R-10 and pectinase
      Boerozym M5, whereas treatment with macerozyme R-10 had a negative effect. When a
      combination of cellulase (0.1%) and pectinase (0.05%) was used, the rate of
      explants with uniformly GUS-positive shoots increased at least twofold. The
      transient expression of reporter genes was also enhanced using sonication (50
      MHz; 2, 4 and 6 s), but stable expression in regenerated shoots following 4 weeks
      of selection did not increase with this treatment. Enzyme treatment alone (0.1%
      cellulase and 0.05% pectinase) was superior to a combined treatment of sonication
      and enzymes with respect to stable transformation. Polymerase chain reaction
      analyses of shoots recovered by grafting from transformation experiments using
      GFP as the reporter gene demonstrated the stable integration of the transgene.
      Regenerated plants were fertile and seeds could be harvested.

PMID- 12789453
TI  - Inhibition of growth of microcultured Hancornia speciosa shoots by 3beta
      hydroxylated gibberellins and one of their C-3 deoxy precursors.
AB  - Gibberellins (GAs) A(1), A(3), A(4) and A(7), all 3beta-hydroxylated, growth
      active GAs, significantly inhibited shoot elongation and the formation of nodes
      in in vitro-grown Hancornia speciosa, as did GA(20), a 3-deoxy precursor of
      GA(1). Ancymidol, an early-stage inhibitor of GA biosynthesis, significantly
      retarded shoot elongation without affecting the formation of nodes. Co
      application of ancymidol and GA(1 )did not overcome the ancymidol-induced growth
      retardation. Trinexapac-ethyl, which can inhibit 3beta-hydroxylation (GA
      activation) and 2beta-hydroxylation (GA inactivation), gave no significant
      response on either shoot elongation or node formation, while two isomers of 16,17
      dihydro GA(5), also inhibitors of GA 3beta-hydroxylation, significantly inhibited
      both shoot growth and the formation of nodes. These unusual results may indicate
      a unique metabolism for GAs in microcultured shoots of H. speciosa.

PMID- 12789454
TI  - Expression of pokeweed antiviral proteins in creeping bentgrass.
AB  - Fungal diseases of creeping bentgrass, an important amenity grass used
      extensively on golf courses, are a serious problem in golf course management.
      Transgenic approaches to improving disease resistance to fungal diseases are
      being explored in many species, and in some cases ribosome-inactivating proteins
      have been found to be effective. We have generated transgenic creeping bentgrass
      plants expressing three forms of ribosome-inactivating proteins from pokeweed,
      which are termed pokeweed antiviral proteins (PAP). PAP-Y and PAP-C are nontoxic
      mutants of PAP; PAPII is the native form of another ribosome-inactivating protein
      from pokeweed. In creeping bentgrass, PAP-C transformants did not accumulate the
      protein, suggesting that it is unstable, and in a field test these plants were
      not protected from infection by the fungal pathogen Sclerotinia homoeocarpa, the
      causal agent of dollar spot disease. PAPII transformants could accumulate stable
      levels of the protein but had symptoms of toxicity; one low-expressing line
      exhibited good disease resistance. PAP-Y transformants accumulated stable levels
      of protein, and under greenhouse conditions they appeared to be phenotypically
      normal.

PMID- 12789452
TI  - Rapid detection of aneuploidy in Musa using flow cytometry.
AB  - We report a procedure for the rapid and convenient detection of aneuploidy in
      triploid Musa using DNA flow cytometry. From a population of plants derived from
      gamma-irradiated shoot tips, plants were selected based on aberrant morphology
      and their chromosome numbers were counted. Aneuploids plants with chromosome
      numbers 2n=31 or 32 were found as well as the expected triploid plants
      (2n=3x=33). At the same time, the nuclear DNA content of all plants was measured
      using flow cytometry. The flow cytometric assay involved the use of nuclei
      isolated from chicken red blood cells (CRBC), which served as an internal
      reference standard. The relative DNA content of individual plants was expressed
      as a ratio of DNA content of CRBC and Musa (DNA index). In order to estimate the
      chromosome number using flow cytometry, the relative DNA content of plants with
      unknown ploidy was expressed as a percentage of the DNA content of triploid
      plants. The classification based on flow cytometry fully agreed with the results
      obtained by chromosome counting. The results indicated that flow cytometry is a
      convenient and rapid method for the detection of aneuploidy in Musa.

PMID- 12789455
TI  - What are we doing and where are we going?

PMID- 12789456
TI  - MIDI face-lift and tricuspidal SMAS-flap.
AB  - Looking tired is enough for many 40-50-years-olds to ask a plastic surgeon for
      prophylactic rejuvenation. They want to achieve good and long lasting effects
      with harmonious features, small scars, and--as they are still very active in
      their professional and private lives--a quick recovery is very important to them.
      We have developed a modification of the short-scar face-lift with solid deep
      support. We call it the MIDI face-lift. MIDI stands for Minimal, Invasive, Deep,
      Intensive. Technical details are as follows. Two half Z-plasties were performed
      at each end of modest skin excision, supra-auriculary and retro-auriculary, to
      avoid even suture edges. By doing so we achieve very unobtrusive scarring. For
      solid SMAS tension we perform SMAS-plication, simple SMAS-flap, or tricuspidal
      SMAS-flap. This is an overview of 200 patients we treated over three years. By
      applying tumescent local anesthesia with adrenaline and ornipressin, and fibrin
      glue at the end of the procedure, we can the draining so that 96% of our patients
      were outpatients. Technical details will be discussed as well as complications,
      adjuvant and alternative procedures. The satisfaction of our patients was high
      (88%) and no major complications have occurred. Only three out of 200 patients
      had to undergo revisionary surgery.

PMID- 12789458
TI  - Sociological aspects of rhinoplasty.
AB  - Although the psychological aspect of the rhinoplasty operation has been a subject
      of interest for a long time, with the exception of a few studies, sociological
      factors have been almost totally ignored. In this prospective study the
      personality characteristics and socioeconomic backgrounds of 216 rhinoplasty
      patients were evaluated. Between 1994 and 2000, a questionnaire and the Minnesota
      Multiphasic Personality Inventory (MMPI) were given preoperatively to 157 females
      and 59 males. The MMPI was also given to age-matched people as a control. Six
      months after surgery, patients were called on the telephone and asked to rate
      their satisfaction. According to questionnaire, a great majority of the
      rhinoplasty patients were young, unmarried women with high education levels. In
      the rhinoplasty group, one or more scales of the inventory were not in the normal
      ranges in 45% of the patients, whereas this proportion in the control group was
      28% (p < 0.01). When MMPI results are considered, female patients of this study
      could be described as egocentric, childish, highly active, impulsive,
      competitive, reactive, perfectionistic about themselves, talkative, and
      emotionally superficial. Male patients could be described as rigid, stubborn,
      over-sensitive, suspicious, perfectionistic, pessimistic, over-reactive, and
      having somatizations. Tension and anxiety with feelings of inferiority were found
      to be characteristics of the male patients. The satisfaction rate after six
      months was reported as 72%. There was no significant correlation between MMPI
      results and demographic variables, nor satisfaction rate. In conclusion, the
      rhinoplasty patients in our study are young people at the very beginning of their
      careers. It could be that their personalities and socioeconomic backgrounds
      combine to make aesthetic surgery rewarding enough, both socially and personally,
      to encourage them to follow through.

PMID- 12789459
TI  - Circular lipectomy with lateral thigh-buttock lift.
AB  - Patients with body contour deformities amongst the challenges that plastic
      surgeons most frequently face. Through the years, many surgical procedures have
      been developed that attempt to solve many forms of body contour deformities while
      optimizing the number of surgical stages within safety limits. In one stage,
      circular lipectomy with lateral thigh and buttock lift and trochanteric
      liposuction corrects deformities of the abdomen, the lateral thighs, the
      buttocks, the supra-gluteal area, the lateral supra-gluteal area, leaving only
      one circular scar that can be covered with a thong. It is performed under
      epidural anesthesia, requires one or two units of autologous blood, one night in
      a hospital, and two or three weeks off work. Thirty-nine patients were operated
      on without any major complications. Results were consistently good and superior
      to patients' expectations.

PMID- 12789460
TI  - Congenital heart disease management in developing countries.

PMID- 12789461
TI  - Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122
      metastases treated in 64 patients.
AB  - PURPOSE: Stereotactic radiosurgery is an alternative option to neurosurgical
      excision in the management of patients with brain metastases. We retrospectively
      analyzed patients with brain metastases of malignant melanoma who were treated at
      our institution for outcome and prognostic factors. PATIENTS AND METHODS: 64
      patients with 122 cerebral metastases were treated with stereotactic radiosurgery
      between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the
      time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at
      that time. The median dose to the 80% isodose line, prescribed to encompass the
      tumor margin, was 20 Gy (range, 15-22 Gy). RESULTS: Neurologic symptoms improved
      in five of twelve symptomatic patients. 41 patients remained asymptomatic or
      unchanged in their neurologic symptoms. Only five patients (8%) temporarily
      worsened neurologically after therapy despite no signs of tumor progression. With
      a mean follow-up time of 9.4 months, actuarial local control was 81% after 1
      year. There was a statistically significant dose and size dependency of local
      tumor control. Median actuarial survival after treatment was 10.6 months.
      Patients without extracerebral tumor manifestation showed a superior survival (p
      = 0.04). CONCLUSIONS: Despite high local tumor control rates, the prognosis of
      patients with cerebral metastases of malignant melanoma remains poor.
      Stereotactic radiosurgery has the potential of stabilizing or improving
      neurologic symptoms in these patients in a palliative setting.

PMID- 12789462
TI  - Radiotherapy for Graves' orbitopathy: results of a national survey.
AB  - BACKGROUND: Graves' orbitopathy (GO) is a widely accepted indication for
      radiation therapy (RT). In conjunction with the German Cooperative Group on
      Radiotherapy for Benign Diseases (GCG-BD), a national survey was conducted in
      order to assess whether or not there is a consensus on the indication for RT and
      various treatment factors which were studied. MATERIAL AND METHODS: A
      questionnaire was circulated to 190 RT institutions to obtain relevant data
      concerning the patients' workload, stage-dependent indication, and diagnostic
      procedures, which were considered to be necessary. Further questions addressed
      details on radiation technique and dose-fractionation schedules, the combined use
      of corticoids, and salvage RT after previous treatment failure following RT.
      RESULTS: With a response rate of 152/190 (80%), the survey is nationally
      representative. Based on the case workload, an estimated annual number of 1,600
      GO cases are treated in German radiotherapy departments. With an 88% consensus,
      stages II-V are the typical indications. 85% considered imaging studies necessary
      for indication and only 48% for laboratory tests. 76% of the institutions used
      total doses in the range of 15-20 Gy, and conventional fractionation was most
      common (57%). 82% used a face mask fixation and 67% CT-based treatment planning.
      Approximately 50% would prescribe salvage RT, and total doses in the range of 20
      40 Gy were considered to be acceptable. CONCLUSIONS: The survey revealed a
      consensus concerning most of the factors studied. We recommend to review the
      patterns of care for RT of other entities of benign diseases and to implement a
      quality assurance program both on national and international levels.

PMID- 12789463
TI  - Californium-252 (252Cf) versus conventional gamma radiation in the brachytherapy
      of advanced cervical carcinoma long-term treatment results of a randomized study.
AB  - BACKGROUND: When photon radiotherapy is applied to cervical carcinoma, it has
      been observed that, despite important progress in radiotherapy technique and
      quality assurance, no significant increase in curative rates has resulted. Among
      the reasons for this is the varying radiosensitivity of different tumor
      subpopulations. Treatment with californium-252 ((252)Cf), as a source of
      gamma/neutron radiation in brachytherapy, provides properties and new treatment
      modalities that help to overcome this factor. PATIENTS AND METHODS: From January
      1985 to June 1993, 227 women with stage IIB and IIIB cervical carcinoma were
      treated in a randomized brachytherapy study as follows: (1) 117 patients (55 with
      stage IIB, 62 with stage IIIB) were treated with (252)Cf during the 1st week of
      therapy by 6 Gy (40 Gy-eq) of the neutron component in point A. Supplementation
      by a 16-Gy dose with (226)Ra or (137)Cs was done in the 5th week. (2) 110
      patients (50 with stage IIB, 60 with stage IIIB) were treated solely by gamma
      radiation ((226)Ra or (137)Cs). A dose of 56 Gy in point A was applied in two
      fractions at the 3rd and 5th week, respectively. The dose of 56 Gy-equivalents
      was completed by external radiation with 40 Gy. The total radiation doses at
      points A and B amounted to 85 Gy and 59 Gy, respectively. The treatment results
      were compared. RESULTS: The overall 5-year survival rate for all stages IIB and
      IIIB was better by 18.9% for (252)Cf patients than for patients receiving
      conventional treatment (75.2% vs. 56.3%, respectively; p < 0.001). In the stage
      IIIB (252)Cf group, it was significantly better by 22.8% than for the
      conventional group (66.1% vs. 43.3%, respectively; p < 0.003). The higher
      survival rate in (252)Cf patients was the result of significantly less local
      relapses compared with patients treated conventionally (12,8% vs. 31.8%; p <
      0.0009). CONCLUSION: The importance of neutron source (252)Cf in the
      brachytherapy of cervical carcinoma by overcoming the tumor resistance to
      conventional photon irradiation has been confirmed.

PMID- 12789464
TI  - Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in
      head and neck cancer. Is there evidence for radioprotection?
AB  - PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced
      acute toxicity by amifostine (A). We investigated this issue in a randomized
      trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus
      amifostine (RC + CT + A) in patients with head and neck cancer. PATIENTS AND
      METHODS: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4
      N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were
      irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2)
      carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were
      applied daily before each radiotherapy session. Acute toxicity was evaluated
      according to the Common Toxicity Criteria (CTC). As for acute xerostomia,
      patients with laryngeal cancer were excluded from evaluation. RESULTS: 50
      patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT +
      A group). Clinical characteristics were well balanced in both treatment groups.
      Amifostine provided reduction in acute xerostomia and mucositis but had no
      obvious influence on Karnofsky performance status, body weight, cutaneous side
      effects, and alopecia. The differences between both groups were statistically
      significant for acute xerostomia and nonsignificant, but with a trend for
      mucositis. CONCLUSIONS: According to our results, there is a radioprotective
      effect on salivary glands and a potential effect on oral mucosa by amifostine in
      postoperative radiotherapy combined with carboplatin. To improve the radio- and
      chemoprotective effects of amifostine in clinical practice, the application of a
      higher dose (> 250 mg) seems to be necessary.

PMID- 12789465
TI  - Early morbidity after radiotherapy with or without chemotherapy in advanced head
      and neck cancer. Experience from four nonrandomized studies.
AB  - BACKGROUND: Data on early treatment-related morbidity after radiotherapy alone
      (RT; 217 patients) or combined with chemotherapy (RT + CT; 182 patients) of head
      and neck squamous cell carcinoma are analyzed. PATIENTS AND METHODS: The patients
      were treated between November 1985 and November 1996 in four Swiss centers that
      independently introduced combined-modality therapy in selected cases of head and
      neck cancer. RT schedules varied among the four centers, but within each
      institution all patients received the same dose-fractionation schedule
      irrespective of whether they had CT or not. The following early morbidity items
      were evaluated: skin, mucosa, larynx, salivary glands, dysphagia, weight loss,
      and toxic death. Toxicity was scored using the EORTC/RTOG scale. RESULTS:
      Although considerable variation was noted among the treatment schedules/centers,
      the main findings are as follows: (1) early morbidity was significantly enhanced
      after all five RT + CT schedules compared with RT alone; (2) typically, a third
      of the patients lost > 10% of their body weight during concurrent RT + CT as
      compared with 10% of the patients receiving RT alone; (3) at 12 weeks, the
      prevalence of grade 2 morbidity was 25-60% after RT + CT as compared with 4-20%
      after RT alone. CONCLUSION: A number of early morbidity items were found to be
      more prevalent and/or more severe after RT + CT than after RT alone.

PMID- 12789467
TI  - Sensitivity of human tumor cells to retinoids or combined treatment with
      retinoids and ionizing radiation is not dependent on RAR-beta 2 induction.
AB  - PURPOSE: The nuclear retinoic acid receptor beta 2 (RAR-beta2) is supposed to be
      a prognostic marker of retinoid sensitivity in patients after retinoid treatment.
      Therefore, we investigated the role of RAR-beta2 induction with respect to
      clonogenic survival of different human tumor cells under retinoid treatment alone
      or in combination with irradiation. MATERIAL AND METHODS: The retinoid
      responsiveness of seven human tumor cell lines (HTB35, HTB43, SCC4, SCC9, MDA
      MB231, HCT116, and CaSki) as well as one normal human skin fibroblast (HSF6) as
      control cells was analyzed by colony formation assay under retinoid and
      retinoid/radiation treatment. Basic mRNA levels of all retinoic acid receptors as
      well as the treatment-dependent modulation of mRNA and protein levels of RAR-beta
      were analyzed by RT-PCR and Western blot analysis under the different treatment
      conditions. RESULTS: It could be shown that the clonogenic inactivation of tumor
      cells under retinoid treatment alone or in combination with irradiation was not
      correlated with the induction of RAR-beta on mRNA and protein level,
      respectively. The control cells (HSF6), however, demonstrated an induction.
      CONCLUSION: The responsiveness of human tumor cells to retinoid treatment alone
      and particularly to combined treatment with irradiation is not necessarily
      associated with an induction of RAR-beta2 as it has been postulated so far. Thus,
      loss of RAR-beta induction in tumors does not seem to be a good prognostic factor
      for successful retinoid/radiation therapy, since RAR-beta-deficient tumors may
      also present strong retinoid responsiveness.

PMID- 12789466
TI  - [Extranodal non-Hodgkin's lymphoma of MALT-type stage I. A case report].
AB  - BACKGROUND: Extranodal non-Hodgkin's lymphoma are mostly localized in the
      gastrointestinal tract. A small number of these lymphoma arise from specialized
      lymphoid cells, the so-called mucosa-associated lymphoid tissue (MALT). We
      describe one case with a metachronous occurrence of a MALT-type lymphoma of the
      conjunctiva of both eyelids and supraglottic larynx. PATIENT AND METHOD: A 56
      year old woman was first treated in August 1990 for a low-grade B-cell lymphoma
      in the conjunctiva of the left eyelid. 42 months later an extranodal B-cell
      lymphoma, located in the conjunctiva of the right eyelid, was found. After a
      father period of 48 months a MALT-type lymphoma arose in the supraglottic larynx.
      The findings of staging examinations were normal. The final diagnosis was low
      grade B-cell lymphoma of the MALT-type, limited to the conjunctival eyelids and
      supraglottic larynx, with the clinical staging of IE A. Treatment consisted of a
      LASER-resection followed by a locoregional radiotherapy, with the dose of 40 Gy.
      RESULTS: Currently no evidence of disease (NED) at all sites can be proven.
      CONCLUSIONS: Extranodal, primary low grade B-cell MALT-type lymphoma are rare. In
      the literature only few cases of each larynx- and conjunctival eyelid involvement
      described. The radiotherapy has been reported to achieve a long time of relapse
      free interval. The present case demonstrates, that even the recurrence of an
      extranodal, primary low-grade B-cell MALT-type lymphoma responds well to local
      radiotherapy and can also have a long period of no evidence of disease.

PMID- 12789468
TI  - In Vivo TGF-beta 3 expression during wound healing in irradiated tissue. An
      experimental study.
AB  - BACKGROUND: Wound-healing disorders frequently present a clinical problem in
      patients with squamous epithelial carcinomas of the head and neck region after
      surgical interventions such as grafts of free flaps in preirradiated graft bed
      tissues. Here, inflammatory changes and the expression of cytokines can lead to
      delayed healing and to the induction of fibrosis. The isoforms of the
      transforming growth factor beta (TGF-beta(1-3)) play a central role in this
      process. While it was possible to experimentally show a fibrosis-inducing
      activity for TGF-beta(1) and TGF-beta(2), a fibrosis-reducing and radioprotective
      effect has been described for TGF-beta(3) on epithelial cells and fibroblasts.
      The influence of irradiation and tissue grafting on the TGF-beta(3) expression,
      however, remains uncertain. The objective of the in vivo study was therefore to
      analyze the expression profile of TGF-beta(3) in the graft bed and in the
      transition area between the graft and the graft bed after irradiation and/or
      after surgery. MATERIAL AND METHODS: A total of 48 Wistar rats (male, weight 300
      500 g) were used in the study. A free myocutaneous gracilis flap was transplanted
      in 30 rats: group 1 (n = 18 rats) no transplantation, only irradiation (3 x 10
      Gy); group 2 (n = 14 rats) transplantation without preoperative irradiation;
      group 3 (n = 16 rats) transplantation following preoperative irradiation (3 x 10
      Gy). The interval between radiotherapy and grafting was 4 weeks. Tissue samples
      were taken perioperatively and postoperatively after 3, 4, 7, 11, 14, 28, and 30
      days from the transition area between the graft and the graft bed and from the
      graft bed itself. The TGF-beta(3) expression was analyzed immunohistochemically
      (labeling index) both qualitatively and quantitatively and checked for
      statistical differences between the groups (p < 0.05). RESULTS: The success rate
      for graft healing was 75% in the group irradiated with 30 Gy, and 86% in the
      nonirradiated group. The rats that were irradiated but not operated on showed
      significantly (p = 0.04) reduced TGF-beta(3) expression in the graft bed
      immediately after the end of the irradiation. Whereas only minor differences in
      TGF-beta(3) expression were observed postoperatively in the graft bed and in the
      transition area between the graft and the graft bed in the group where a graft
      was carried out without preirradiation, the group that was preirradiated with
      subsequent grafting showed a significantly reduced expression in the bed (p =
      0.018). CONCLUSION: After irradiation, it was possible to measure reduced TGF
      beta(3) expression in the irradiated graft bed. The exogenous application of TGF
      beta(3) could therefore present a new therapeutic approach for improving wound
      healing through radioprotection of nontransformed epithelial cells and
      fibroblasts after preoperative radiotherapy and surgery.

PMID- 12789469
TI  - Inverse automated treatment planning with and without individual optimization in
      interstitial permanent prostate brachytherapy with high- and low-activity 125I.
AB  - PURPOSE: To determine whether dose distribution achieved with treatment plans
      using high- and low-activity (125)I implants differs. PATIENTS AND METHODS: Based
      on intraoperative transrectal ultrasound scans of 71 patients, inverse automated
      treatment plans (IATP) were performed with 15.5-kBq (0.42-mCi) and 25.2-kBq (0.68
      mCi) (125)I implants using a commercial 3-D planning system (Variseed). A
      prescription dose of 145 Gy in 98% of the prostate volume (V100), a maximum dose
      to the urethra of 250 Gy (D1), and a maximum dose to 10% of the anterior rectal
      wall of 145 Gy (D10) were required. The plans were manually corrected, if
      necessary. RESULTS: In the IATP, a better dose coverage of the prostate was found
      for high-activity seeds (V100 of 98% vs 84%). The prostate dose values increased
      with the prostate volume. After manual optimization, the differences were only
      marginal with a prostate V100 of 99% for both activities, a urethra D1 of 247 Gy
      and 239 Gy, and a rectum D10 of 135 Gy and 124 Gy for high- and low-activity
      seeds. Low-activity seeds required more sources (66 vs 47) and needles (24 vs 17;
      all numbers are median values). CONCLUSIONS: Concerning the prostate dose
      coverage, high-activity seeds are superior in the IATP. After manual adjustment,
      the dose values for the prostate and the organs at risk are similar. Considering
      a supposedly decreased toxicity and a shorter implantation time for a lower
      number of seeds, we recommend high-activity seeds for experienced teams.

PMID- 12789470
TI  - An outbreak of rubella aboard a ship of the German Navy.
AB  - BACKGROUND: During May and June 1996, an outbreak of rubella occurred offshore
      aboard a ship of the German Navy. The outbreak spread among 330 crew members over
      a period of 9 weeks, ending 2 days after the ship's return. This is the first
      detailed epidemiological investigation of a rubella outbreak on a ship,
      describing temporal progression, clinical manifestations, immunization status and
      seroprevalence of the population exposed. PATIENTS AND METHODS: Outbreak
      investigation using a questionnaire, health records and rubella serology
      (hemagglutination inhibition (HI) test and EIA). RESULTS: Of the 330 crew members
      298 (90%) participated in the investigation. The outbreak was continuous without
      a peak and ended abruptly after the ship's return. It resulted in 20 cases, 11 of
      which were clinically symptomatic. A total of 35 (12%) crew members were
      susceptible to rubella prior to the outbreak, resulting in an attack rate of 57%.
      The highest risk for infection was linked to accommodation aboard the ratings
      deck (chi(2)-test, p = 0.004) with most favorable conditions of transmission.
      Only 9% of the participating crew were able to provide complete proof of their
      immunization status. The positive predictive value of a past history of rubella
      for the presence of antibodies against rubella was 59%. CONCLUSION: The
      transmission of rubella that we describe aboard a ship was facilitated by the
      unusually close proximity of the crew and their insufficient immunity.
      Documentation of immunization was inadequate in this population.

PMID- 12789471
TI  - Cervical human papillomavirus infection in Tunisian women.
AB  - BACKGROUND: It is well established that certain types of human papillomavirus
      (HPV) are the sexually transmitted agents etiologically linked to cervical
      cancer. Sexual habits have been shown to be a major determining factor for HPV
      infection. A large study was carried out to investigate the prevalence and risk
      factors associated with cervical infection with HPV in Tunisian women. MATERIALS
      AND METHODS: PCR and restriction enzyme digestion were used to characterize HPV
      cervical infection in 106 Tunisian married women and 51 legal prostitutes.
      Epidemiological data were collected and correlated with HPV molecular genotyping.
      RESULTS: There was a higher relative frequency of HPV-DNA in prostitutes (39%)
      than in married women (14%) (p = 0.001). Molecular analyses of HPV types showed
      the most prevalent type in prostitutes to be HPV-16, a high-risk oncogenic type.
      In married women, the most prevalent type was HPV-6 which is associated with a
      low risk for cervical cancer. HPV-DNA detection was markedly increased in young
      adult women and in those having recent sexual experience. CONCLUSION: Cervical
      HPV infection in Tunisia is less frequent than in other African countries, but
      far from uncommon. The decrease of HPV prevalence in older women, regardless of
      their sexual behavior, may result from an efficient immune response acquired with
      age.

PMID- 12789472
TI  - Chlamydia pneumoniae infection and restenosis in patients with coronary heart
      disease.
AB  - BACKGROUND: The aim of this study was to establish whether Chlamydia pneumoniae
      is implicated in the development of restenosis in patients with coronary heart
      disease (CHD) after percutaneous transluminal coronary angioplasty (PTCA).
      PATIENTS AND METHODS: 67 patients were selected for study after they underwent
      control angiography after PTCA. Sera were tested for anti-chlamydial antibodies
      with a genus specific ELISA and a species-specific microimmunofluorescence test
      (MIFT). Oropharyngeal specimens were examined for the presence of antigen with a
      Chlamydia immunofluorescence test (IFT), C. pneumoniae IFT and semi-nested PCR.
      In addition, anamnestic findings were also included. To determine the general
      level of antibodies, an age- and sex matched control group of 180 persons was
      also examined for Chlamydia and C. pneumoniae serology. RESULTS: Coronary
      angiography revealed that 31 of the 67 patients had developed a restenosis. There
      was no significant correlation between serological and angiographic findings.
      However, the MIFT showed a higher positive rate, especially in IgA, in the
      restenosis group. C. pneumoniae was detected in the oropharynx by PCR and/or IFT
      in 20.8% and 16.0% of the cases in patients with and without a restenosis. PCR
      found more C. pneumoniae-positive cases in the restenosis patients than IFT. No
      association was found between the detection of Chlamydia antigen and serology.
      The women with restenosis were more frequently smokers (p = 0.012). Men with
      restenosis were significantly older (p = 0.015). C. pneumoniae serology based on
      the rELISA or the MIFT did not show any correlation with restenosis. CONCLUSION:
      No evidence was found to suggest that positive C. pneumoniae serology is a risk
      factor for the development of restenosis. However, whether the species-specific
      serological test, especially for IgA-antibodies, and the detection of C.
      pneumoniae in oropharyngeal specimens by PCR might be reliable diagnostic markers
      in these cases remains to be determined.

PMID- 12789473
TI  - Stenotrophomonas (Xanthomonas) maltophilia as an emerging opportunistic pathogen
      in association with HIV infection: a 10-year surveillance study.
AB  - BACKGROUND: Stenotrophomonas (Xanthomonas) maltophilia has been increasingly
      reported as a nosocomial opportunistic pathogen, responsible for serious
      infectious complications in immunocompromised patients. At present very limited
      information is available concerning its clinical significance in the setting of
      HIV infection. PATIENTS AND METHODS: A retrospective survey of clinical and
      microbiological records of 1,374 HIV-infected patients referring to our tertiary
      care center during a 10-year period (1991-2000) was performed to identify all
      episodes of S. maltophilia infection and analyze epidemiological, clinical and
      laboratory variables. The episodes of S. maltophilia bacteremia were compared
      with those caused by non-typhoid Salmonella spp. occurring in HIV-infected
      patients referring to our center during the same period, in order to evaluate
      eventual predisposing risk factors. RESULTS: 61 episodes of S. maltophilia
      infection were observed in 59 HIV-infected patients: sepsis/bacteremia in 48
      cases (78.7%), lower airways infection in five, urinary tract infection in four,
      pharyngitis in two, lymphadenitis and liver abscess in one case each. 47 of 61
      episodes (77%) of S. maltophilia infection occurred as nosocomial disease (i.e.
      were diagnosed after the 3rd day of hospitalization) and bacterial isolates
      showed an elevated resistance profile against many beta-lactam compounds,
      aztreonam, imipenem and aminoglycosides. At the same time, 38 episodes of
      bacteremia due to non-typhoid Salmonella spp. were diagnosed in our patients, 13
      of which were nosocomial infections. CONCLUSION: When compared with non-typhoid
      Salmonella spp. bacteremia, a significantly higher risk of developing S.
      maltophilia disseminated infection was seen in association with advanced
      immunodeficiency, leukopenia-neutropenia, central venous catheterization, prior
      broad-spectrum antimicrobial therapy and/or corticosteroid treatment.

PMID- 12789474
TI  - Prions and orthopedic surgery.
AB  - Prions are a novel class of infectious agents that cause subacute encephalopathy
      in man and animals as human Creutzfeldt-Jakob disease (CJD), sheep scrapie and
      bovine spongiform encephalopathy (BSE). Previously, prions were shown to be
      transmitted by neuro- and ophthalmosurgical measures and by application of brain
      derived therapeutic hormones. Recently, prions have been detected in blood
      specimens of experimentally infected monkeys indicating a principal threat to
      transfusion medicine, furthermore in human or bovine materials used in
      reconstructive surgery. In this article the risk of prion transmission from the
      surgeon to the patient or vice versa during (orthopedic) surgery is reevaluated
      including the issues of blood transfusion. This is accomplished based on recent
      epidemiologic findings and biometric calculations on the spread of prions in
      animals and humans as well as in terms of experimental data on artificially
      contaminated medical materials and devices. The overall risk of prion
      transmission in orthopedic surgery is considered very low if adequately prepared
      and sterilized materials and devices are used.

PMID- 12789475
TI  - HIV/HTLV co-infection: frequency and epidemiological characteristics among
      patients admitted to an Italian hospital.
AB  - BACKGROUND: Human T-cell leukemia/lymphoma viruses (HTLV) and HIV share identical
      modes of transmission and co-infections may be detected in populations that are
      highly exposed to common risk factors. MATERIALS AND METHODS: A total of 599
      serum samples from HIV-positive patients attending our outpatient clinic during
      the last semester of 2000 were tested to assess the prevalence of HTLV co
      infection in both Italian (n = 472) and non-European HIV-infected patients (n =
      127). RESULTS: 72 samples were positive for HTLV-II. Most of the HTLV-II-positive
      patients were Italian (71/72, 98.6%) and 98.5% of them had acquired the HIV
      infection through use of intravenous recreational drugs. CONCLUSION: These data
      demonstrate a high HTLV-II exposure among HIV-positive intravenous drug users in
      our area which was not previously considered to be an area of endemicity for HTLV
      II.

PMID- 12789476
TI  - Prognostic factors for death from visceral leishmaniasis in Teresina, Brazil.
AB  - BACKGROUND: A possible strategy to reduce fatality rates of visceral
      leishmaniasis is to identify prognostic factors that can be easily assessed and
      used as an aid to clinical decision-making. PATIENTS AND METHODS: A case-control
      study was developed in Teresina, Brazil, in which cases were patients who died
      during treatment (n = 12) and controls (n = 78) comprised a random sample of
      patients who were alive when treatment was finished. RESULTS: Variables
      significantly associated with death were severe anemia, fever for more than 60
      days, diarrhea and jaundice. The prognostic system had a sensitivity of 85.7% and
      a specificity of 92.5%. CONCLUSION: The prognostic model developed in this study
      had satisfactory performance and might be useful in developing countries, since
      it is simple and inexpensive. However, it is still preliminary and needs to be
      improved and validated using larger and more recent samples.

PMID- 12789477
TI  - Mediastinal mass with Dysphagia in an elderly patient.
AB  - We report the use of endoscopic techniques for successful diagnosis in a case of
      atypical esophageal tuberculosis. Tuberculosis of the esophagus is an unusual
      presentation of this disease, having been estimated to occur in 0.15% of the
      people who die of tuberculosis. A few cases of possible primary tuberculous
      esophagitis have been described. This report describes a patient with dysphagia
      who appeared to have esophageal tuberculosis without HIV and in the absence of
      other signs of tuberculosis. The patient responded promptly to treatment with
      tuberculostatics.

PMID- 12789478
TI  - Aortic homograft endocarditis caused by Rhodotorula mucilaginosa.
AB  - Serious infections caused by Rhodotorula spp. are rare and usually occur in
      immunocompromised people, especially in patients with tumors and long-time use of
      indwelling central venous catheters. We report a case of Rhodotorula mucilaginosa
      homograft endocarditis in an otherwise healthy man, which was successfully
      treated by surgery in combination with amphotericin B and subsequently
      intraconazole.

PMID- 12789479
TI  - Pacemaker endocarditis due to Propionibacterium acnes.
AB  - Propionibacterium acnes belongs to the cutaneous flora of humans; it is often
      considered to be contaminant but has also been found to be a pathogen in human
      diseases. It is an uncommon causal agent in infective endocarditis and appears to
      have a predilection for prosthetic valves and foreign bodies. We describe a case
      of pacemaker endocarditis which shows that so-called harmless bacteria like P.
      acnes must be considered to be potential pathogens.

PMID- 12789480
TI  - Emergency endovascular stent-grafting for infected pseudoaneurysm of brachial
      artery.
AB  - The use of covered stents in an infected field is controversial. It is generally
      recommended that infected aneurysms be treated using autografts or allografts. We
      report a case of infected brachial pseudoaneurysms that developed after medical
      debridement of a methicillin-resistant Staphylococcus aureus (MRSA)-infected
      wound of the right arm and emergency brachial artery bypass-grafting using the
      saphenous vein, which was successfully treated by endovascular stent-grafting
      followed by antibiotic administration. The present case suggests that
      endovascular stent-grafting prevents rupture and occlusion of infected aneurysms
      and enables the continued administration of antibiotics.

PMID- 12789481
TI  - False-positive Mycobacterium tuberculosis culture revealed by restriction
      fragment length polymorphism analysis.
AB  - BACKGROUND: The microbiological analysis of respiratory specimens is the most
      reliable approach to diagnose active pulmonary tuberculosis. PATIENT AND METHODS:
      We report a 60-year-old female patient (index patient) who underwent diagnostic
      bronchoscopy for chronic cough. No acid-fast bacilli were detected in bronchial
      washings. Although cough subsided with symptomatic treatment, Mycobacterium
      tuberculosis grew on egg-based media after 12 weeks. A false-positive culture
      result was suspected. Chart review and DNA fingerprinting were carried out.
      RESULTS: The bronchoscope used to examine the index patient was previously used
      for a 30-year-old patient (source patient) with smear- and culture-positive
      pulmonary tuberculosis. Restriction fragment length polymorphism (RFLP) analysis
      based on the IS 6110 element confirmed that the two strains were identical.
      CONCLUSION: Cross-contamination is a reason for false-positive cultures with M.
      tuberculosis and should be suspected in patients with a low clinical probability
      for active tuberculosis.

PMID- 12789482
TI  - Intestinal perforations in a premature infant caused by Bacillus cereus.
AB  - Although Bacillus cereus is a ubiquitous bacterium, the incidence of neonatal
      infections is very low with only a few cases of B. cereus infections in neonates
      reported in the literature. We report the case of a premature infant with
      multiple intestinal perforations and an abdominal B. cereus infection. The
      initial course was characterized by severe cardiovascular shock, anemia,
      thrombocytopenia and disseminated intravascular coagulation, leading to
      periventricular leukomalacia, alopecia capitis and toxic epidermal necrolysis.
      The possible role of B. cereus-associated enterotoxins for the clinical
      manifestations are discussed. Our case confirms previous reports of severe
      clinical symptoms in B. cereus infection in premature neonates. We speculate that
      the systemic complications of B. cereus infection are at least partly related to
      the effect of B. cereus-associated enterotoxins.

PMID- 12789483
TI  - [Pain in children and adolescents--results of an exploratory epidemiological
      study].
AB  - AIM OF THE STUDY: The objective of this exploratory study was to examine the
      prevalence of overall pain generally and combinations of different pain
      locations, as well as their location, intensity, and duration in children and
      adolescents. METHODS: After consent was granted by the local ethical committee
      and the Ministry for Education, Research, Science and Culture, modified versions
      of the structured pain questionnaire of Perquin et al. were submitted to 1077
      parents, children,and adolescents in the Lubeck region of Germany. Of the 1077
      questionnaires distributed, 1030 were returned (95.6%), and 991 of the 1030
      questionnaires (96.2%) could be included in the analysis. RESULTS: The prevalence
      of overall pain during the preceding 3 months was 80.1%, while the prevalence of
      pain in more than one region of the body during the preceding 3 months was 66.3%.
      Of the children and adolescents, 57% had headaches, 43.2% suffered from abdominal
      pain, 41.6% had limb pain, 32.9% had back pain, and 30% suffered from sore
      throats during the previous 3 months. A total of 30.7% of the children and
      adolescents with pain reported that the pain had already lasted for more than 6
      months. CONCLUSIONS: Pain in general is very frequent in children and
      adolescents. Further studies are required to investigate chronic pain in children
      and adolescents.

PMID- 12789484
TI  - [Neuropeptide release in the dura mater encephali in response to nitric oxide-
      relevance for the development of vascular headaches?].
AB  - Nitric oxide (NO) and calcitonin gene-related peptide (CGRP), potent vasodilators
      in the meninges,may be involved in the pathophysiology of vascular headaches such
      as migraine pain. NO donators can provoke headache attacks in migraineurs and
      increased levels of CGRP have been found in the venous outflow from the head
      during migraine attacks. We therefore examined the effect of both NO and CGRP on
      dural blood, a process which may parallel nociceptive processes in the meninges.
      1. Arterial blood flow was measured in the exposed dura mater encephali of the
      rat using laser Doppler flowmetry. Local application of different NO donors
      (SNAP,NONOate, and NOC-12) caused dose-dependent increases in meningeal blood
      flow. CGRP(8-37) at 10(-4) M did not significantly change the basal flow but
      attenuated increases in blood flow caused by the NO donors at concentrations of
      10(-5)-10(-3) M.2. In another series of experiments, the hemisected skulls of
      adult Wistar rats, complete with intact dura mater, were filled with oxygenated
      synthetic interstitial fluid (SIF) and the CGRP content of this fluid was
      assessed every 5 min. When the NO donator NONOate, at concentrations of 10(-5)
      10(-3) M, was added to the SIF, or when the SIF was bubbled with NO gas (1000 ppm
      in N(2) atmosphere) instead of carbogen, CGRP release increased in a
      concentration-dependent manner. We conclude that the vasodilatory effect of NO
      that causes increased meningeal blood flow is in part the result of both
      stimulating the release of CGRP and promoting the vasodilatory action of CGRP.
      Since NO donors such as nitroglycerin are known to provoke headache and CGRP is
      released during migraine pain, the NO-stimulated CGRP release may be relevant for
      the development of vascular headaches that are accompanied by meningeal
      hyperaemia.

PMID- 12789485
TI  - [Tissue toxicity of local anesthetics. An in vivo trial].
AB  - AIM: Local anesthetics are often administered intra-articularly after knee
      surgery. The aim of this study was to determine differences in irritancy of local
      anesthetics in an in vivo test performed on the chorioallantoic membrane of hen's
      eggs (HET-CAM test) to evaluate the specific irritation score. METHOD: After
      incubation for 9 days, the chorioallantoic membrane was prepared and then exposed
      to different local anesthetics (Naropin, Scandicain,Carbostesin,Xyloneural).
      RESULTS: We found no irritating values for the tested substances. No vascular
      injuries of the chorioallantoic membrane could be detected. Therefore, the
      irritation score was measured according to the standard protocol with an
      irritation score=0. CONCLUSION: Our results show that local anesthetics often
      used in clinics do not provoke severe vascular injuries as a sign of tissue
      toxicity. Therefore, the customary concentrations can be recommended for clinical
      use.

PMID- 12789486
TI  - ["Facial pain" in German-language medical textbooks on pain (1990-2002)].
AB  - INTRODUCTION: The aim of this study was to determine how frequently and to what
      extent facial pain--particularly musculoskeletal and neuropathic pain--has been
      considered in German-language textbooks on pain published between 1990 and 2002.
      METHODS: Relevant textbooks were identified by hand search and by search in
      electronic bibliographic databases. A quantitative analysis was carried out by
      counting and comparing the number of pertinent pages in the textbooks. For the
      assessment of the medical-scientific quality of the information on
      musculoskeletal face pain, a checklist was used based on comparisons with the
      current state of the scientific literature on facial pain. RESULTS: Of 231
      textbooks on pain, 28 consider the topic of "facial pain." Of the 1923 pages
      dedicated to facial pain and headache, musculoskeletal and neuropathic facial
      pain make up 7% and 17%, respectively. Headache, in contrast, accounts for 71% of
      all pages. Only ten contributions on musculoskeletal facial pain could be
      assessed, two of which exhibit a high medical-scientific quality. CONCLUSIONS:
      The data suggest that facial pain is underrepresented in German-language
      textbooks on pain. In addition, a considerable part of the information given on
      musculoskeletal facial pain does not correspond to the current state of the
      scientific literature. This may lead to under- or overdiagnosis and to under- or
      overtreatment.

PMID- 12789487
TI  - [Local treatment of rheumatic diseases with the 5-HT3 receptor antagonist
      tropisetron].
AB  - Local injection of the 5-HT3 receptor antagonist tropisetron manifests a distinct
      analgesic effect in various local diseases of the locomotor system such as
      tendinopathies, peri-arthropathies,myofascial pain syndrome, in trigger points,
      and in inflammatory joint processes.This effect corresponds to that exerted by
      local anesthetics in general use such as lidocaine and prilocaine among others,
      but the effect lasts considerably longer. The reason for this finding is found in
      a simultaneous antiphlogistic effect of the 5-HT3 receptor antagonist as
      evidenced by animal experiments and clinical data.

PMID- 12789488
TI  - [Novel potential uses of thalidomide in the management of pain? A review of the
      literature].
AB  - Thalidomide was introduced as a sedative and antiemetic agent to the European
      market in the late 1950s. However, it soon became clear that a hitherto unheard
      of incidence of severe birth defects was due to the maternal use of thalidomide
      and the drug was withdrawn from the market. Despite its teratogenesis,
      thalidomide is currently being rediscovered because of its known spectrum of
      anticachectic, antiemetic, mildly hypnotic, anxiolytic, anti-inflammatory,
      antiangiogenic, and analgesic properties. The mechanism of action of thalidomide
      is probably based on its immunomodulatory effect, namely the suppression of
      production of tumor necrosis factor alpha and the modulation of interleukins. A
      striking but not well-known finding is the effectiveness of thalidomide as an
      analgesic or analgesic adjuvant. During the early era of thalidomide use, the
      drug was shown to enhance the analgesic efficacy of a combined treatment with
      acetylsalicylic acid, phenacetin, and caffeine (APC) by testing "normal
      volunteers, using electrical stimulation of teeth." The combination of
      thalidomide and APC was superior to other combinations (APC alone, APC and
      codeine) with respect to both the total analgesic effect and the duration of this
      analgesic effect. In 1965 thalidomide was found to be effective in treating the
      painful subcutaneous manifestations of the leprosy-associated erythema nodosum
      leprosum, a condition for which it eventually was approved by the United States
      Food and Drug Administration in 1998. In an animal model of neuropathic pain
      (chronic constriction injury), thalidomide was shown to reduce both mechanical
      allodynia and thermal hyperalgesia. Recent studies documented the analgesic
      efficacy of thalidomide in treating painful mucocutaneous aphthous ulcers
      associated with HIV syndrome and Behcet's disease.However, to date there are no
      recent clinical trials that are specifically designed to explore the analgesic
      potential of thalidomide. In view of the current basic research and clinical
      findings,we suggest to investigate the potential benefits of thalidomide in
      severe pain conditions that respond poorly to common pain management approaches
      such as neuropathic pain, postherpetic neuralgia, or central pain phenomena.
      Because its mechanism of action is distinct from that of other drugs such as
      steroids, thalidomide offers the possibility of a combined treatment with other
      agents with nonoverlapping toxicities. We conclude that thalidomide, when used
      properly,may enrich the therapeutic regimen in the management of some pain
      related conditions.

PMID- 12789489
TI  - [Complex regional pain syndrome. Sympathetic reflex dystrophy and causalgia].
AB  - Complex regional pain syndromes (CRPS) occur as the inadequate response to
      painful trauma in a distal extremity. With CRPS I (sympathetic reflex dystrophy),
      no lesion of the nerve is present. Aside from sensory disturbances, burning deep
      spontaneous pain and mechanical allodynia are characteristic. Disturbances in the
      skin blood circulation,sweating,edema,and trophic disturbances of the skin,
      joints, and bones are typical. Reduction in muscle strength, tremor, and late
      dystonic changes comprise the motor disturbances. All symptoms are distributed in
      the distal extremity and not limited to the region of the peripheral nerves.
      Complex regional pain syndrome II (causalgia),develops following a partial
      peripheral nerve lesion. The distally generalized symptoms are identical.
      Successful therapy depends on an early start of interdisciplinary treatment. In
      addition to the pain therapy,physiotherapy plays a decisive role in
      rehabilitation. During the acute phase, freedom from pain at rest and
      retrogression of the edema must be achieved. With slight spontaneous pain, a
      conservative therapeutic method may be applied (analgesics, rest, raised
      position). In case of insufficient improvement and in difficult cases, the effect
      of intervention (sympathetic blockade) should be tested and possibly a blockade
      series performed. After reduced spontaneous pain,physiotherapy should be
      increased stepwise.

PMID- 12789490
TI  - Migraine aura dynamics after reverse retinotopic mapping of weak excitation waves
      in the primary visual cortex.
AB  - Akinematical model for excitable wave propagation is analyzed to describe the
      dynamics of a typical neurological symptom of migraine. The kinematical model
      equation is solved analytically for a linear dependency between front curvature
      and velocity. The resulting wave starts from an initial excitation and moves in
      the medium that represents the primary visual cortex. Due to very weak
      excitability the wave propagates only across a confined area and eventually
      disappears. This cortical excitation pattern is projected onto a visual hemifield
      by reverse retinotopic mapping. Weak excitability explains the confined
      appearance of aura symptoms in time and sensory space. The affected area in the
      visual field matches in growth and form the one reported by migraine sufferers.
      The results can be extended from visual to tactile and to other sensory symptoms.
      If the spatiotemporal pattern from our model can be matched in future
      investigations with those from introspectives, it would allow one to draw
      conclusions on topographic mapping of sensory input in human cortex.

PMID- 12789491
TI  - A recurrent network for landmark-based navigation.
AB  - A new type of network is proposed that can be applied to landmark navigation. It
      solves the guidance task, that is, it finds a nonvisually marked location using
      knowledge concerning its spatial relation to other, visible landmarks. The path
      to the searched location is not disturbed if a landmark is not visible for some
      time. The network can also describe findings obtained by experiments with insects
      and rodents, where the position of the landmarks has been changed after training.
      In this net, recognition does not occur by searching for a match between a
      pattern seen and the same pattern being stored but by searching for a match
      between a pattern seen with a prediction calculated from different data. A simple
      extension allows a unique match of the landmarks seen with the items stored in
      memory. With this extension a recognition of the individual landmark is not
      necessary. A specific output unit of the network can be interpreted in such a way
      as to show properties of place cells found in vertebrates and the function of the
      network proposed here as to determine the input to a place cell. The model can
      explain the observation that a given place cell can also be active when the
      animal moves in a different environment. An extension is discussed of how the
      network could be exploited for recognition-triggered response that allows animals
      to follow fixed routes.

PMID- 12789492
TI  - Neuron classification based on temporal firing patterns by the dynamical analysis
      with changing time resolution (DCT) method.
AB  - Spike train data of many neurons can be obtained by multirecording techniques;
      however, the data make it difficult to estimate the connective structure in a
      large network. Neuron classification should be helpful in that regard, assuming
      that multiple neurons having similar connections with other neurons show a
      similar temporal firing pattern. We propose a novel method for classifying
      neurons based on temporal firing patterns of spike train data called the
      dynamical analysis with changing time resolution (DCT) method. The DCT method can
      evaluate temporal firing patterns by a simple algorithm with few arbitrary
      factors and automatically classify neurons by similarity of temporal firing
      patterns. In the DCT method, temporal firing patterns were objectively evaluated
      by analyzing their dependence on temporal resolution. We confirmed the
      effectiveness of the DCT method using actual spike train data.

PMID- 12789493
TI  - Neural computations in the tiger salamander and mudpuppy outer retinae and an
      analysis of GABA action from horizontal cells.
AB  - A neural network architecture based on the neural anatomy and function of retinal
      neurons in tiger salamander and mudpuppy retinae is proposed to study basic
      aspects of early visual information processing. The model predictions for the
      main response characteristics of retinal neurons are found to be in agreement
      with neurophysiological data, including the antagonistic role of horizontal cells
      in the outer plexiform layer. The examination of possible gamma-aminobutyric acid
      (GABA) action from horizontal cells suggests that GABA(A) alone, GABA(B) alone,
      or their weighted combination can generate the response characteristics observed
      in bipolar cells.

PMID- 12789494
TI  - Stimulus-dependent onset latency of inhibitory recurrent activity.
AB  - This paper gives an explanation for the experimentally observed onset latencies
      of the inhibitory responses that vary from a few milliseconds to hundreds of
      milliseconds in systems where the conduction delays are only several milliseconds
      in the feedback pathways. To do this we use a simple mathematical model. The
      model consists of two delay differential equations (DDE) where the nonlinear
      relation between the postsynaptic potential and the firing frequency of the
      neuron population arises from the stoichiometry of the transmitter-receptor
      kinetics. The parameters of the model refer to the hippocampal feedback system,
      and the modeling results are compared with corresponding experiments.

PMID- 12789495
TI  - Possible functional roles of phase resetting during walking.
AB  - The walking rhythm is known to show phase shift or "reset" in response to
      external impulsive perturbations. We tried to elucidate functional roles of the
      phase reset possibly used for the neural control of locomotion. To this end, a
      system with a double pendulum as a simplified model of the locomotor control and
      a model of bipedal locomotion were employed and analyzed in detail. In these
      models, a movement corresponding to the normal steady-state walking was realized
      as a stable limit cycle solution of the system. Unexpected external perturbations
      applied to the system can push the state point of the system away from its limit
      cycle, either outside or inside the basin of attraction of the limit cycle. Our
      mathematical analyses of the models suggested functional roles of the phase reset
      during walking as follows. Function 1: an appropriate amount of the phase reset
      for a given perturbation can contribute to relocating the system's state point
      outside the basin of attraction of the limit cycle back to the inside. Function
      2: it can also be useful to reduce the convergence time (the time necessary for
      the state point to return to the limit cycle). In experimental studies during
      walking of animals and humans, the reset of walking rhythm induced by
      perturbations was investigated using the phase transition curve (PTC) or the
      phase resetting curve (PRC) representing phase-dependent responses of the
      walking. We showed, for the simple double-pendulum model, the existence of the
      optimal phase control and the corresponding PTC that could optimally realize the
      aforementioned functions in response to impulsive force perturbations. Moreover,
      possible forms of PRC that can avoid falling against the force perturbations were
      predicted by the biped model, and they were compared with the experimentally
      observed PRC during human walking. Finally, physiological implications of the
      results were discussed.

PMID- 12789496
TI  - Agrobacterium-mediated transformation of niger [ Guizotia abyssinica (L. f.)
      Cass.] using seedling explants.
AB  - A protocol was developed for Agrobacterium-mediated genetic transformation of
      niger [ Guizotia abyssinica (L.f.) Cass.] using hypocotyl and cotyledon explants.
      Hypocotyls and cotyledons obtained from 7-day-old seedlings were co-cultivated
      with Agrobacterium tumefaciens strain EHA101/pIG121Hm that harbored genes for
      beta-glucuronidase (GUS), kanamycin, and hygromycin resistance. Following co
      cultivation, the hypocotyl and cotyledon explants were cultivated on MS medium
      containing 1 mg/l 6-benzylaminopurine (BA) for 3 days in darkness. Subsequently,
      hypocotyl and cotyledon explants were transferred to selective MS medium
      containing 1 mg/l BA, 10 mg/l hygromycin, 10 mg/l kanamycin, and 500 mg/l
      cefotaxime. After 6 weeks, hypocotyls and cotyledons produced multiple
      adventitious shoot buds, and these explants were subcultured to MS medium
      containing 1 mg/l BA, 30 mg/l hygromycin, and 30 mg/l kanamycin. After a further
      3 weeks, the explants (along with developing shoot buds) were subcultured to MS
      medium containing 1 mg/l BA, 50 mg/l kanamycin, and 50 mg/l hygromycin for
      further selection. Transgenic plants were obtained after rooting on half-strength
      MS medium supplemented with 0.1 mg/l alpha-naphthaleneacetic acid, 50 mg/l
      kanamycin, and 50 mg/l hygromycin and were confirmed by GUS histochemical assay
      and polymerase chain reaction analysis. Genomic Southern blot hybridization
      confirmed the incorporation of the neomycin phosphotransferase II gene into the
      host genome.

PMID- 12789497
TI  - Ethylene inhibitors and low kanamycin concentrations improve adventitious
      regeneration from apricot leaves.
AB  - An improved method for adventitious regeneration from apricot leaves is
      described. The use of the ethylene inhibitors silver thiosulphate (30-60 micro M)
      or aminoethoxyvinylglycine (0.5 micro M) increased regeneration percentages in
      Helena and Canino apricot cultivars and also the consistency of results from
      different experiments. Use of "Pure Agar" also improved regeneration from Helena
      leaves as compared with agargel or agarose. Regeneration rates for Canino were
      dependent on the medium in which the shoots were micropropagated. When different
      antibiotics were tested for their influence on regeneration, the combination of
      cefotaxime (0.13 m M) plus vancomycin (0.63 m M), which efficiently controls
      Agrobacterium growth, also increased regeneration percentages in Helena two-fold
      but did not affect regeneration in Canino. Kanamycin, an antibiotic widely used
      for selection of nptII transformed cells, promoted more rapid regeneration and
      higher regeneration rates from Helena leaves when added at low concentrations
      (8.6 and 17.1 micro M). With this improved procedure, regeneration from apricot
      leaves has been increased more than 200% as compared with rates reported
      previously.

PMID- 12789498
TI  - Use of an inducible reporter gene system for the analysis of auxin distribution
      in the moss Physcomitrella patens.
AB  - The plant hormone auxin plays a major role in a variety of growth and
      developmental responses, even in the more ancient plants-for example, cell
      differentiation in mosses. Nevertheless, almost nothing is known about the
      distribution of auxin during moss development. To address this question, we
      characterised auxin distribution in the moss Physcomitrella patens using auxin
      inducible reporter gene systems. Stable transgenic Physcomitrella plants were
      produced expressing the beta-glucuronidase (GUS) gene driven by the auxin
      inducible promoters GH3 and DR5, respectively. Both fusions showed remarkable
      differences with respect to auxin-induced promoter strength and expression
      kinetics. A detailed characterisation of the GUS expression pattern in different
      developmental stages revealed that the highest auxin concentrations were in
      dividing and ontogenetic young cells.

PMID- 12789500
TI  - A method for inflorescence proliferation.
AB  - Most perennial plants must pass through a long juvenile phase of vegetative
      development before they are capable of flowering. We have developed a method
      specifying inflorescence proliferation to bypass juvenility and maintain the
      adult phase. Bamboo ( Bambusa edulis) inflorescences were amplified by incubation
      in Murashige and Skoog medium supplemented with 0.1 mg/l thidiazuron. Mutant
      albino inflorescences also proliferated in this medium. This method is equally
      effective with dicotyledonous plants. Ginseng ( Panax ginseng) buds were
      incubated in B5 medium supplemented with 1 mg/l benzyladenine and 1 mg/l
      gibberellic acid; new inflorescences developed from the base of the explants.
      Ginseng flowers were parthenocarpic and some of the fruit proliferated in vitro.
      Using the inflorescences as the material of somatic embryogenesis, we
      demonstrated that these were not mutations. The regenerated plants still had a
      juvenile phase and grew normally.

PMID- 12789499
TI  - Roles of the reactive oxygen species-generating peroxidase reactions in plant
      defense and growth induction.
AB  - Extracellularly secreted plant peroxidases (POXs) are considered to catalyze the
      generation of reactive oxygen species (ROS) coupled to oxidation of plant hormone
      indole-3-acetic acid (IAA) and defense-related compounds salicylic acid (SA),
      aromatic monoamines (AMAs) and chitooligosaccharides (COSs). This review article
      consists of two parts, which describe H(2)O(2)-dependent and H(2)O(2)-independent
      mechanisms for ROS generation, respectively. Recent studies have shown that plant
      POXs oxidize SA, AMAs and COSs in the presence of H(2)O(2) via a conventional POX
      cycle, yielding the corresponding radical species, such as SA free radicals.
      These radical species may react with oxygen, and superoxide (O(2)(.-)) is
      produced. Through the series of reactions 2 moles of O(2)(.-) can be formed from
      1 moles of H(2)O(2), thus leading to oxidative burst. It has been revealed that
      the ROS induced by SA, AMAs and COSs triggers the increase in cytosolic Ca(2+)
      concentration. Actually POXs transduce the extracellular signals into the redox
      signals that eventually stimulate the intracellular Ca(2+) signaling required for
      induction of defense responses. On the other hand, IAA can react with oxygen and
      plant POXs in the absence of H(2)O(2), by forming the ternary complex enzyme-IAA
      O(2), which readily dissociates into enzyme, IAA radicals and O(2)(.-). This
      article covers the recent reports showing that extracellularly produced hydroxy
      radicals derived from O(2)(.-) mediate the IAA-induced cell elongation. Here a
      novel model for IAA signaling pathway mediated by extracellular ROS produced by
      cell-wall POXs is proposed. In addition, possible controls of the IAA-POX
      reactions by a fungal alkaloid are discussed.

PMID- 12789501
TI  - Cost-effective in vitro propagation methods for pineapple.
AB  - We have developed an efficient and cost-effective method for commercial
      micropropagation of Smooth Cayenne pineapple. In vitro shoots were used as
      starting materials, and either longitudinal sections of the shoots or leaf bases
      were used as the explants to regenerate shoots. When these explants were used,
      the axillary meristems, which usually remain quiescent during shoot
      multiplication, were able to form new shoots. Subsequent to the regeneration
      step, additional multiplication was achieved inside a 10-l Nalgene vessel with
      shoots immersed in liquid medium for 5-10 min/h (periodic immersion bioreactor,
      PIB). The shoots were then induced to form roots and transferred to soil. Using
      the above micropropagation method and the PIB, we produced 6,000-8,000 shoots
      from two initial shoots in less than 6 months. The clonal fidelity of propagated
      plants was tested in Costa Rican and Indonesian pineapple farms.

PMID- 12789502
TI  - Stable genetic transformation of Vigna mungo L. Hepper via Agrobacterium
      tumefaciens.
AB  - Vigna mungo is one of the large-seeded grain legumes that has not yet been
      transformed. We report here for the first time the production of morphologically
      normal and fertile transgenic plants from cotyledonary-node explants inoculated
      with Agrobacterium tumefaciens carrying binary vector pCAMBIA2301, the latter of
      which contains a neomycin phosphotransferase ( nptII) gene and a beta
      glucuronidase (GUS) gene ( uidA) interrupted with an intron. The transformed
      green shoots, selected and rooted on medium containing kanamycin, tested positive
      for nptII and uidA genes by polymerase chain reaction (PCR) analysis. These
      shoots were established in soil and grown to maturity to collect the seeds.
      Mechanical wounding of the explants prior to inoculation with Agrobacterium, time
      lag in regeneration due to removal of the cotyledons from explants and a second
      round of selection at the rooting stage were found to be critical for
      transformation. Analysis of T(0) plants showed the expression and integration of
      uidA into the plant genome. GUS activity in leaves, roots, flowers, anthers and
      pollen grains was detected by histochemical assay. PCR analysis of T(1) progeny
      revealed a Mendelian transgene inheritance pattern. The transformation frequency
      was 1%, and 6-8 weeks were required for the generation of transgenics.

PMID- 12789503
TI  - Transformation of triploid bermudagrass (Cynodon dactylon x C. transvaalensis cv.
      TifEagle) by means of biolistic bombardment.
AB  - A transformation system for triploid bermudagrass ( Cynodon dactylon x C.
      transvaalensis cv. TifEagle) was established with a biolistic bombardment
      delivery system. Embryogenic callus was induced from stolons and maintained on
      Murashige and Skoog's medium supplemented with 30 microM dicamba, 20 microM
      benzylaminopurine, and 100 mg/l myo-inositol. Using the hygromycin
      phosphotransferase ( hpt) gene as the selectable marker gene, we obtained 75
      transgenic lines from 18 petri dishes bombarded. Integration of the hpt gene into
      genomic DNA and transcription of hpt was confirmed by Southern and Northern blot
      analyses, respectively. Through suspension culture screening, we obtained
      homogeneously transformed plants showing stable transcription of the hpt gene.

PMID- 12789504
TI  - Efficiency of transient transformation in tobacco protoplasts is independent of
      plasmid amount.
AB  - We describe an optimized protocol for the transient transformation of tobacco
      protoplasts mediated by polyethylene-glycol (PEG). As expected, the quantitative
      beta-glucuronidase (Gus) activity driven by pCaMVGus was dependent on the amount
      of plasmid used. Nevertheless, we demonstrate by an immunodetection method that
      transformation efficiency did not depend on the amount of plasmid used but on the
      limitation imposed by cell competence. In fact, we obtained the same percentage
      of transformed cells (about 60%) using a wide range of plasmid concentrations
      (0.1-10 microg per test). Finally, we show that, when we used two plasmid types
      in a mixture at a concentration ranging from 0.1 to 10 microg for each, all
      transformed cells expressed proteins encoded by both plasmids. Transient
      expression and co-transformation experiments are routinely used methods and,
      probably, the major results from this work were assumed by many researchers in
      this field, but our data experimentally support this assumption.

PMID- 12789505
TI  - Stable transformation of Theobroma cacao L. and influence of matrix attachment
      regions on GFP expression.
AB  - We describe a protocol for Agrobacterium-mediated genetic transformation of
      Theobroma cacao L. using cotyledonary explants from primary somatic embryos (SEs)
      and A. tumefaciens strain AGL1. Transgenic plants carrying the visible marker,
      gene green fluorescent protein ( EGFP), the selectable marker gene neomycin
      phosphotransferase II ( NPTII), the class I chitinase gene from cacao ( Chi), and
      tobacco nuclear matrix attachment regions (MARs) in different combinations were
      successfully produced via regeneration of secondary SEs. The presence of the Chi
      gene or MARs did not influence the number of transgenic plants produced compared
      to the marker genes alone. However, the inclusion of MARs contributed to
      increased mean GFP expression in the population of transgenics. Additionally, the
      presence of MARs reduced the occurrence of gene silencing and stabilized high
      levels of GFP expression in lines of transgenic plants multiplied via reiterative
      somatic embryogenesis. Ninety-four transgenic plants were acclimated in a
      greenhouse and grown to maturity. Detailed growth analysis indicated that there
      were no differences in various growth parameters between transgenic and non
      transgenic SE-derived plants. Seeds produced from two genetic crosses with one of
      the transgenic lines were analyzed for EGFP expression-a near-perfect 1:1
      segregation was observed, indicating that this line resulted from the insertion
      of a single locus of T-DNA.

PMID- 12789506
TI  - Assembly of cholera toxin B subunit full-length rotavirus NSP4 fusion protein
      oligomers in transgenic potato.
AB  - A CTB-NSP4(175) fusion gene encoding the entire 175-aa murine rotavirus NSP4
      enterotoxin protein was transferred into Solanum tuberosum cells by Agrobacterium
      tumefaciens-mediated transformation. The CTB-NSP4(175) enterotoxin fusion gene
      was detected in the genomic DNA of transformed leaves by PCR DNA amplification.
      Synthesis and assembly of the full-length CTB-NSP4(175) fusion protein into
      oligomeric structures of pentamer size was detected in transformed tuber extracts
      by immunoblot analysis. The binding of CTB-NSP4(175 )fusion protein pentamers to
      intestinal epithelial cell membrane receptors was quantified by G(M1)-ganglioside
      enzyme-linked immunosorbent assay (G(M1)-ELISA). The ELISA results showed that
      CTB-NSP4(175) fusion protein was 0.006-0.026% of the total soluble tuber protein.
      The synthesis of CTB-NSP4(175) monomers and their assembly into biologically
      active oligomers in transformed potato tubers demonstrates the feasibility of
      using edible plants for the synthesis of enterocyte-targeted full-length
      rotavirus enterotoxin antigens that retain all of their pathogenic epitopes for
      initiation of a maximum mucosal immune response.

PMID- 12789507
TI  - Polyester synthesis in transplastomic tobacco (Nicotiana tabacum L.): significant
      contents of polyhydroxybutyrate are associated with growth reduction.
AB  - The pathway for synthesis of polyhydroxybutyrate (PHB), a polyester produced by
      three bacterial enzymes, was transferred to the tobacco plastid genome by the
      biolistic transformation method. The polycistronic phb operon encoding this
      biosynthetic pathway was cloned into plastome transformation vectors. Following
      selection and regeneration, the content and structure of plant-produced
      hydroxybutyrate was analysed by gas chromatography. Significant PHB synthesis was
      limited to the early stages of in vitro culture. Within the transformants, PHB
      synthesis levels were highly variable. In the early regeneration stage, single
      regenerates reached up to 1.7% PHB in dry weight. At least 70% of plant-produced
      hydroxybutyric acid was proven to be polymer with a molecular mass of up to 2,500
      kDa. PHB synthesis levels of the transplastomic lines were decreasing when grown
      autotrophically but their phb transcription levels remained stable. Transcription
      of the three genes is divided into two transcripts with phbB being transcribed
      separately from phbC and phbA. In mature plants even low amounts of PHB were
      associated with male sterility. Fertility was only observed in a mutant carrying
      a defective phb operon. These results prove successful expression of the entire
      PHB pathway in plastids, concomitant, however, with growth deficiency and male
      sterility.

PMID- 12789508
TI  - A carnation anthocyanin mutant is complemented by the glutathione S-transferases
      encoded by maize Bz2 and petunia An9.
AB  - Particle bombardment was used to elucidate the function of Flavonoid3, a late
      acting anthocyanin gene of the ornamental plant, carnation ( Dianthus
      caryophyllus L.). The fl3 mutation conditions dilute anthocyanin coloration that
      closely resembles phenotypes produced by the anthocyanin mutants bz2 of maize and
      an9 of petunia. Bz2 and An9 encode glutathione S-transferases (GSTs) involved in
      vacuolar sequestration of anthocyanins. Constructs containing either of these or
      another late-function maize gene, Bronze1 (UDPglucose:flavonol 3- O
      glucosyltransferase), were introduced via microprojectile bombardment into fl3
      petals. Complementation resulted only from Bz2 and An9, indicating that Fl3
      encodes a GST involved in the transport of anthocyanins to the vacuole. The
      observed result in carnation, an angiosperm phylogenetically distant from maize
      and petunia, indicates that GST activity might be a universal step in the
      anthocyanin pathway. Microprojectile bombardment was used to identify late
      pathway anthocyanin mutations, which may be responsible for the pale anthocyanin
      coloration of important cultivars in many species but which can be difficult to
      characterize by other means.

PMID- 12789509
TI  - Chromosome doubling procedures of onion (Allium cepa L.) gynogenic embryos.
AB  - A novel approach for chromosome doubling that consists of treating embryos
      instead of parts of micropropagated plants was investigated. Following 2-year
      trials, amiprofos-methyl (APM) was found to be superior to oryzalin on the basis
      of a lower toxicity, and we were able to narrow the range of concentrations of
      APM. The addition of 2% dimethyl sulphoxide (DMSO) and 1% Triton X-100 to 25
      microM APM had no effect in all treatments. A final experiment with 6,658 embryos
      demonstrated that a 2-day treatment in liquid media supplemented with 50 microM
      APM was the most successful with respect to chromosome doubling-36.7% of the
      plants were diploid-but the survival rate was reduced to 52.5% of that of the non
      treated control. A 2-day treatment in liquid medium supplemented with 25 microM
      APM or a 2-day treatment on solid medium with 50 microM APM resulted in the
      production of diploids at a frequency of 28.9% and 21.3%, respectively. These may
      represent alternative methods for chromosome doubling since compared to the
      untreated control these two treatments reduced the survival rate by only about
      24%. Final ploidy and fertility of the large proportion of induced mixoploid
      plants (up to 30.3%) need to be evaluated in further studies.

PMID- 12789510
TI  - The S haplotypes lacking SLG in the genome of Brassica rapa.
AB  - Self-incompatibility (SI) discriminating self- and non-self pollen is regulated
      by S-locus genes in Brassica. In most of the S haplotypes, a highly polymorphic S
      locus glycoprotein ( SLG) gene is tightly linked to genes for the SI
      determinants, S-receptor kinase ( SRK) and SP11, although the precise function of
      SLG in SI has not been clarified. In the present study, we performed DNA gel blot
      analysis for S(32), S(33), and S(36) haplotypes of Brassica rapa showing normal
      SI phenotypes and concluded that there might be no SLG in their genome. RNA gel
      blot analysis of the SLG-less S haplotypes indicated the possible existence of
      eSRK transcripts in the stigma. These three S haplotypes are useful resources to
      discern the molecular mechanism of the SI reaction without SLG.

PMID- 12789511
TI  - Analysis of regulatory elements of the promoter and the 3' untranslated region of
      the maize Hrgp gene coding for a cell wall protein.
AB  - Hydroxyproline-rich glycoproteins (HRGP) are structural components of the plant
      cell wall. Hrgp genes from maize and related species have a conserved 500 bp
      sequence in the 5'-flanking region, and all Hrgp genes from monocots have an
      intron located in the 3' untranslated region. To study the role of these
      conserved regions, several deletions of the Hrgp gene were fused to the beta
      glucuronidase ( GUS) gene and used to transform maize tissues by particle
      bombardment. The overall pattern of GUS activity directed by sequential deletions
      of the Hrgp promoter was different in embryos and young shoots. In embryos, the
      activity of the full-length Hrgp promoter was in the same range as that of the
      p35SI promoter construct, based on the strong 35S promoter, whereas in the fast
      growing young shoots it was 20 times higher. A putative silencer element specific
      for young shoots was found in the -1,076/-700 promoter region. Other major cis
      elements for Hrgp expression are probably located in the regions spanning -699/
      510 and -297/-160. Sequences close to the initial ATG and mRNA leader were also
      important since deletion of the region -52/+16 caused a 75% reduction in promoter
      activity. The presence of the Hrgp intron in the 3' untranslated region changed
      the levels of GUS activity directed by the Hrgp and the 35S promoters. This
      pattern of activity was complex, and was dependent on the promoter and cell type
      analysed.

PMID- 12789512
TI  - Efficient regeneration systems for two closely related Moricandia species
      possessing a C3 or C3-C4 intermediate photosynthetic character.
AB  - The C(3)-C(4) intermediate species Moricandia arvensis ( Brassicaceae) and its
      closest C(3) relative, Moricandia moricandioides, represent model species for
      studying the C(3)-C(4) photosynthetic character relative to the C(3) phenotype.
      In order to enable transgenic analyses in these two species, optimal regeneration
      systems based on leaf and/or stem internode segments were developed, and
      genotypes suitable for in vitro tissue culture were identified. Evaluation of the
      regeneration capability of 30 M. arvensis genotypes and 12 M. moricandioides
      genotypes revealed that all could form callus. However, shoots were only produced
      by 40% of the M. arvensis genotypes and 8% of the M. moricandioides genotypes.
      The two Moricandia species showed significant genotypic differences with respect
      to callus formation and shoot regeneration. For the 12 regenerative M. arvensis
      genotypes, 29-100% of the explants developed shoots, while 71% of the explants
      from the single regenerable M. moricandioides genotype formed shoots. The
      genotype used, the choice of stem or leaf explants and the composition of the
      medium (i.e. concentrations of different hormones and salts) significantly
      affected plant regeneration (chi-square analyses, P<0.05). Whole plants could be
      obtained in the greenhouse after 3-3.5 months for M. arvensis genotypes and after
      4-4.5 months for M. moricandioides.

PMID- 12789513
TI  - Sexual modification of female spinach seeds (Spinacia oleracea L.) by irradiation
      with ion particles.
AB  - The female seeds of a spinach plant (Spinacia orelacea L.) were exposed to He
      (12.5 MeV/n) and C (18.3 MeV/n) ions in order to investigate the effects of ion
      particles on sex expression. He ions did not affect germination rates or
      flowering at doses up to 50 Gy. C ions did not affect germination rates or
      flowering at doses up to 15 Gy, but a dose of 25 Gy resulted in many plants with
      morphological aberrations. When unexposed female plants were grown without cross
      fertilization for 10 weeks after sowing, 5.6-14.3% of the plants produced anthers
      from female flowers. These sex-modified plants could self-pollinate and form
      seeds, which expressed only female organs. Conversely, gynomonoecious plants were
      induced from these female seeds by exposure to He ions (5-50 Gy) and C ions (5-25
      Gy) without any difference in the rates of flowered progeny. Moreover,
      andromonoecious plants were induced from female seeds by exposure to He ions at
      50 Gy. These results suggest that the sex of a spinach plant is expressed as a
      flexible phenotype, converging from female to gyno- and andromonoecy after
      exposure to ion particles.

PMID- 12789514
TI  - Encapsulation of nodal cuttings and shoot tips for storage and exchange of
      cassava germplasm.
AB  - We report the encapsulation of in vitro-derived nodal cuttings or shoot tips of
      cassava in 3% calcium alginate for storage and germplasm exchange purposes. Shoot
      regrowth was not significantly affected by the concentration of sucrose in the
      alginate matrix while root formation was. In contrast, increasing the sucrose
      concentration in the calcium chloride polymerisation medium significantly reduced
      regrowth from encapsulated nodal cuttings of accession TME 60444. Supplementing
      the alginate matrix with increased concentrations of 6-benzylaminopurine and
      alpha-naphthaleneacetic acid enhanced complete plant regrowth within 2 weeks.
      Furthermore, plant regrowth by encapsulated nodal cuttings and shoot tips was
      significantly affected by the duration of the storage period as shoot recovery
      decreased from almost 100% to 73.3% for encapsulated nodal cuttings and 94.4% to
      60% for shoot tips after 28 days of storage. The high frequency of plant regrowth
      from alginate-coated micropropagules coupled with high viability percentage after
      28 days of storage is highly encouraging for the exchange of cassava genetic
      resources. Such encapsulated micropropagules could be used as an alternative to
      synthetic seeds derived from somatic embryos.

PMID- 12789515
TI  - A rooting procedure for lentil (Lens culinaris Medik.) and other hypogeous
      legumes (pea, chickpea and Lathyrus) based on explant polarity.
AB  - The present study assessed the rooting response of lentil nodal segments in
      relation to explant polarity, hormone, salt and carbohydrate concentrations of
      the medium. Nodal segments of lentil with an axillary bud cultured in an inverted
      orientation (apical end in medium) showed higher rooting frequencies than
      explants cultured in a normal orientation (basal end in medium). The highest
      rooting percentage (95.35%) and average number of shoots regenerated per explant
      (2.4) were obtained from explants placed in an inverted orientation on Murashige
      and Skoog (MS) medium salts with 3% sucrose, supplemented with 5 microM indole
      acetic acid (IAA) and 1 microM kinetin (KN). Reducing or increasing phytohormone
      concentration did not alter significantly root regeneration of inverted explants.
      Sucrose at 3% allowed higher root regeneration frequencies compared to 1.5%
      sucrose. MS full concentration permitted regeneration of longer shoots with more
      nodes per regenerated shoot, compared to MS half-strength, which regenerated more
      shoots of shorter length and with less nodes. Inverted nodal segments of other
      hypogeous legumes (pea, chickpea and Lathyrus) also exhibited higher rooting
      frequencies than explants cultured in a normal orientation on MS medium with 3%
      sucrose and supplemented with 5 microM IAA and 1 microM KN. The most novel
      application of this study is the culture of nodal segments of hypogeous legumes
      in an inverted orientation. This procedure is a considerable improvement over
      other published procedures concerning in vitro rooting of lentil, pea, chickpea
      and Lathyrus.

PMID- 12789516
TI  - High frequency plant regeneration from immature embryos of an elite barley
      cultivar (Hordeum vulgare L. cv. Morex).
AB  - An efficient plant regeneration system was developed for Hordeum vulgare L.
      'Morex' barley, an important United States malting cultivar. The protocol was
      based on a series of experiments involving the sizes of immature embryos and the
      culture media. We found that the embryo size is critical for the establishment of
      embryogenic callus. Smaller embryos (0.5-1.5 mm) showed a much higher ability to
      produce embryogenic callus capable of regenerating green plants with fewer
      albinos than did the larger embryos (1.6-3.0 mm). Either 3 mg/l 2,4
      dichlorophenoxyacetic acid or dicamba in modified Murashige and Skoog's (MS)
      medium was optimum for the induction of embryogenic callus. The embryogenic
      callus maintained high regeneration during six subcultures in the callus
      induction medium. Efficient shoot regeneration was obtained on modified MS medium
      containing 0.5-1.0 mg/l 6-benzylaminopurine (BA). Regenerated shoots were rooted
      on half-strength MS medium containing 0.2 mg/l IBA. Plants were successfully
      transferred to soil and grown to maturity in the greenhouse. This efficient plant
      regeneration system provides a foundation for generating transgenic plants of
      this important barley cultivar.

PMID- 12789517
TI  - Shoot production in squash (Cucurbita pepo) by in vitro organogenesis.
AB  - Seedling-derived cotyledon explants of squash ( Cucurbita pepo L.) of commercial
      cultivars True French, Ma'yan and Goldy were regenerated in vitro on Murashige
      and Skoog medium augmented with 1 mg/l benzyladenine. After 4 weeks in culture
      small shoots and buds regenerated only on the most proximal cotyledon edge.
      Culture on an elongation medium with a reduced cytokinin concentration (0.1 mg/l)
      with or without 1 mg/l gibberellic acid (GA(3)) facilitated the recovery of
      shoots. Fresh shoots could be recovered at each subculture of the regenerating
      mass. Peak productivity was during the third cycle of subculture, and shoot
      production ceased after the fifth subculture. Culture on elongation medium
      supplemented with GA(3) was 55% more effective with respect to overall shoot
      production than that on medium without GA(3), with 22 shoots recovered in total
      per explant from the former. Regeneration occurred under both light and dark
      conditions. All of the shoots tested were diploid. The shoots were rooted and
      transferred to the greenhouse where they grew and flowered normally.

PMID- 12789518
TI  - Improving loblolly pine somatic embryo maturation: comparison of somatic and
      zygotic embryo morphology, germination, and gene expression.
AB  - Clonal production of loblolly pine ( Pinus taeda L.) through somatic
      embryogenesis has the potential to meet the increasing industrial demands for
      high-quality uniform raw materials. A major barrier to the commercialization of
      this technology is the low quality of the resulting embryos. Twenty-five newly
      initiated loblolly pine genotypes were followed through the process of liquid
      culture establishment, embryo maturation, germination, and retrieval from
      cryogenic storage. A maturation medium, capable of promoting the development of
      loblolly pine somatic embryos that can germinate, is presented that combines 1/2
      P6 modified salts, 2% maltose, 13% polyethylene glycol 8000 (PEG), 5 mg/l
      abscisic acid (ABA), and 2.5 g/l Gelrite. A procedure for converting and
      acclimating germinants to growth in soil and greenhouse conditions is also
      described. A set of somatic seedlings, produced from the maturation medium,
      showed 100% survival when planted in a field setting. Somatic seedlings showed
      normal yearly growth relative to standard seedlings from natural seed. The
      quality of the resulting embryos was examined and compared to that of zygotic
      embryos using such parameters as morphology, dry weight, germination performance,
      and gene expression. All of the observations that were made support the
      conclusion that even with the new maturation medium somatic embryos grow
      approximately only halfway through the normal sequence of development and then
      prematurely discontinue growth.

PMID- 12789519
TI  - Vegetative propagation of Quercus suber L. by somatic embryogenesis. I. Factors
      affecting the induction in leaves from mature cork oak trees.
AB  - Somatic embryogenesis was induced in expanding leaves from epicormic shoots
      forced to sprout from segments of branches collected from several hundred-year
      old cork oak trees. Following a basic protocol previously defined for leaves
      taken from seedlings of this species, several factors were studied to improve the
      response. The induction frequency was significantly higher when the length of
      exposure to growth regulators was increased from 7 to 30 days. The combined
      application of NAA and BAP was essential for induction. Although both regulators
      had a very significant influence, their interaction was not significant,
      suggesting independent roles. Leaf size had a crucial effect, because beyond a
      certain threshold, embryogenesis could not be obtained. Embryogenic lines were
      maintained via repetitive embryogenesis on hormone-free medium for more than 2
      years.

PMID- 12789520
TI  - Vegetative propagation of Quercus suber L. by somatic embryogenesis. II. Plant
      regeneration from selected cork oak trees.
AB  - The regeneration of somatic seedlings from selected 100-year-old cork oak trees
      is reported. The induction of somatic embryogenesis from leaves of epicormic
      shoots was significantly affected by genotype, harvesting time and their
      interaction. Leaves from all five selected trees produced somatic embryos when
      the segments of branches used as sources of epicormic shoots were collected in
      May. Genotype, but not the level of photosynthetically active radiation, affected
      the proliferation of the embryogenic lines and the number of detachable embryos
      that could be obtained from them. Genotype also affected several steps leading to
      conversion of somatic embryos, from germination to complete acclimatisation of
      somatic seedlings. Almost 40% of the somatic embryos from all lines germinated,
      showing coordinated root and shoot growth. Although the mean percentage of
      recovery for the whole process was low, plants could be regenerated from four of
      the five trees tested.

PMID- 12789521
TI  - A new transformation-regeneration procedure in the model legume Lotus japonicus:
      root explants as a source of large numbers of cells susceptible to Agrobacterium
      mediated transformation.
AB  - We describe herein a simple and efficient transformation procedure for the
      production of transgenic Lotus japonicus plants. In this new procedure,
      dedifferentiated root explants, used as starting material, are the source of a
      large number of cells that are competent for the regeneration procedure, with a
      high susceptibility to Agrobacterium infection. The application of this protocol
      resulted in a tenfold increase in the number of transformants produced by a
      single plant in comparison to the widely used hypocotyl transformation procedure.
      Furthermore, our procedure allowed the use of intact plants stored for a long
      time at 4 degrees C, thus providing a potential continuous supply of explants for
      transformation experiments. The overall time of incubation under tissue culture
      conditions required to obtain a plant transferable into soil is 4 months. The
      transgenic nature of the transformants was demonstrated by the detection of beta
      glucuronidase (GUS) activity in the primary transformants and by molecular
      analysis. Stable transformation was indicated by Mendelian segregation of the
      hygromycin selectable marker and of the gusA activity after selfing of the
      transgenic plants.

PMID- 12789522
TI  - Binary transformation systems based on 'shooter' mutants of Agrobacterium
      tumefaciens: a simple, efficient and universal gene transfer technology that
      permits marker gene elimination.
AB  - A simple transformation procedure with a positive selection scheme using the
      expression of the isopentenyl transferase ( ipt) gene of transfer DNA (T-DNA)
      'shooter' mutants of Agrobacterium tumefaciens was elaborated. After comparing
      several 'shooter' mutants we found that particular strains frequently produced
      phenotypically normal shoots after co-culturing with tobacco leaf explants.
      Shoots selected for normal phenotype showed apical dominance and could be rooted
      with the same efficiency as non-transformed shoots. When binary vectors were
      introduced into these strains, stably integrated binary vector T-DNA sequences
      were found in some regenerants, which were produced under non-selective
      conditions on growth-regulator-free medium. Such phenotypically normal
      transformants typically lacked a stably integrated ipt gene. Normal looking
      shoots could also be produced in tomato, muskmelon and sweet pepper.

PMID- 12789525
TI  - Long-term expression of the uidA gene in Gladiolus plants under control of either
      the ubiquitin, rolD, mannopine synthase, or cauliflower mosaic virus promoters
      following three seasons of dormancy.
AB  - UidA silencing did not occur following three seasons of dormancy for 23
      independently transformed lines of Gladiolus plants carrying the bar- uidA fusion
      gene under control of either the cauliflower mosaic virus 35S (CaMV 35S),
      ubiquitin ( UBQ3), mannopine synthase ( mas2), or rolD promoters. The highest
      levels of GUS (beta-glucuronidase) expression were observed in callus, shoots,
      and roots of plants carrying the bar- uidA fusion gene under control of the CaMV
      35S promoter and in shoots and roots of greenhouse-grown plants that contained
      the rolD promoter. There was no major difference in GUS expression when plants
      carrying the fusion gene driven by either the CaMV 35S, mas2, or UBQ3 promoters
      were grown in vitro as compared to growth in the greenhouse, although plants
      containing the rolD promoter expressed at 4- to 11-fold higher levels in shoots
      and roots, respectively, when grown in the greenhouse. The levels of GUS
      expression in greenhouse-grown plants were higher in roots than shoots for all
      four promoters. Of the 21 plants analyzed, 20 contained one to three copies of
      the bar- uidA fusion gene. Of the 23 plants analyzed, 11 had rearrangements of
      the transgene, but without apparent effects on levels of GUS expression.

PMID- 12789523
TI  - Establishment of a highly efficient transformation system for pepper (Capsicum
      annuum L.).
AB  - Application of modern genetic manipulation has been limited in pepper ( Capsicum
      annuum L.) due to the lack of an efficient transformation system. Following the
      development of an efficient protocol for in vitro regeneration of pepper
      cotyledons, we investigated the key factors affecting transformation and
      established a highly efficient genetic transformation system using the pepper
      cotyledon as starting material. In this system, cotyledon explants are
      preconditioned for 2 days on kanamycin (km)-free DM1 medium [Murashige and Skoog
      (MS) salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l sucrose,
      5,000 mg/l DJ nutrients and a hormone combination of 1.0 mg/l indoleacetic acid
      (IAA) and 5.0 mg/l 6-benzyladenine (BA) solidified with 0.7% agar, pH 5.8],
      followed by co-cultivation with Agrobacterium tumefaciens on DM1 for 2 days and
      delay selection on DM1 with 500 mg/l carbenicillin (carb) for 2 days. The
      explants are then placed on DM1 containing 10 mg/l AgNO(3), 50 mg/l km-sulfate
      and 500 mg/l carb. After 4-5 weeks, the explants with buds are transferred to EM1
      medium (MS salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l
      sucrose, 5,000 mg/l DJ nutrients, 10 mg/l AgNO(3) and a hormone combination of
      1.0 mg/l IAA, 3.0 mg/l BA and 2.0 mg/l gibberellic acid, solidified with 0.7%
      agar, pH 5.8) with 50 mg/l kanamycin and 500 mg/l carbenicillin for the
      elongation of buds. After 3-6 weeks, 1- to 2-cm-long elongated shoots are excised
      and planted on RM1 medium (MS basal medium supplemented with a hormone
      combination of 0.2 mg/l NAA and 0.1 mg/l IAA, solidified with 0.8% agar, pH 5.8)
      with 25 mg/l km and 200 mg/l carb for rooting. We tested four genotypes of
      pepper, and all presented a high differentiation efficiency (81.3% on average),
      elongation rate (61.5%) and rooting efficiency (89.5%). Polymerase chain reaction
      analysis results showed that 40.8% of the regenerated plantlets were transgenic
      plants.

PMID- 12789524
TI  - Transgene expression in broccoli (Brassica oleracea var. italica) clones
      propagated in vitro via leaf explants.
AB  - We have developed an efficient protocol for the in vitro propagation of
      transgenic broccoli plants using leaf explants as starting material. A high
      frequency of shoot formation from leaf explants was obtained on Murashige and
      Skoog medium containing benzyladenine (BA, 5 mg/l) and naphthaleneacetic acid
      (0.5 mg/l). Frequent subcultures of existing shoots and shoot clusters to medium
      containing only BA (2 mg/l) promoted rapid shoot multiplication. The use of a 1:1
      mixture of Agargel and Gelrite in the rooting medium increased the number of
      healthy roots per rooted plant. Applying this protocol, we obtained thousands of
      clonal rooted plantlets within 6 months from a transgenic broccoli plant carrying
      the cry1Ac and cry1C genes from Bacillus thuringiensis associated with kanamycin
      and hygromycin selectable markers, respectively. Thirty randomly selected clones
      that had been propagated for 1 year on medium containing kanamycin (50 mg/l) all
      showed resistance to both kanamycin and hygromycin. Genomic DNA and total soluble
      proteins were isolated from 16 of these clones. Polymerase chain reaction
      analysis indicated that the cry1Ac and cry1C genes were both maintained. ELISA
      assays showed that all of the clones produced a high level of Cry1Ac protein
      similar to the original transgenic plant; however, most clones had significantly
      lower levels of Cry1C protein than the original plant. This variation indicates
      that it is important to evaluate transgene expression in transgenic clones
      propagated long-term in vitro. In vitro propagation starting from leaf explants
      was also successful with other transgenic and non-transgenic Brassica oleracea
      materials, including broccoli, cauliflower, and collard.

PMID- 12789526
TI  - Expression of CCAAT-binding factor antisense transcripts in reproductive tissues
      affects plant fertility.
AB  - We have previously isolated a CCAAT-binding factor B subunit gene ( BnCBF-B) from
      Brassica napus that is widely expressed in different plant tissues and whose role
      is still unknown. To investigate the importance of this transcription factor
      subunit in plant reproductive tissues, we targeted antisense BnCBF-B transcripts
      to the tapetum of transgenic B. napus plants. Of the 24 independent
      transformants, 13 yielded reduced quantities of viable pollen, of which five were
      unable to produce the elongated siliques indicative of normal seed set. The
      decrease in pollen viability probably resulted from the precocious degeneration
      of the tapetal cell layer observed in these plants. Surprisingly, the male
      sterile phenotype was also accompanied by a decrease in female fertility, which
      could be due to the expression of the antisense BnCBF-B transcripts in the female
      reproductive structures of the transgenic plants. These results suggest that the
      BnCBF-B gene plays a critical non-redundant role in plant reproductive tissues.

PMID- 12789527
TI  - Tetraploid Artemisia annua hairy roots produce more artemisinin than diploids.
AB  - Hairy root cultures of diploid Artemisia annua L. (clone YUT16) grow rapidly and
      produce the antimalarial sesquiterpene artemisinin. Little is known about how
      polyploidy affects the growth of transformed hairy roots and the production of
      secondary metabolites. Using colchicine, we produced four stable tetraploid
      clones of A. annua L. from the YUT16 hairy root clone. Analysis showed major
      differences in growth and artemisinin production compared to the diploid clone.
      Tetraploid clones produced up to six times more artemisinin than the diploid
      parent. This study provides an initial step in increasing our understanding of
      the role of polyploidy in secondary metabolite production, especially in hairy
      roots.

PMID- 12789528
TI  - Molecular detection of a bacterial contaminant Bacillus pumilus in symptomless
      potato plant tissue cultures.
AB  - An aberrant random amplified polymorphic DNA (RAPD) marker in genomic DNA of
      tissue culture plantlets was frequently observed during a comparison of DNA
      fingerprints derived from potato germplasm grown in tissue culture and the field.
      The RAPD marker was cloned, sequenced and determined to be of bacterial origin. A
      bacterial contaminant was isolated from the tissue culture plants and identified
      as a Bacillus pumilus. A set of sequence characterised amplified region (SCAR)
      primers were designed from the sequence of the cloned fragment and tested for the
      specific detection of B. pumilus. Polymerase chain reaction-restriction fragment
      length polymorphisms (PCR-RFLPs) were also used to generate B. pumilus profiles
      specific to our isolate in order to test and confirm the sequence homology of
      amplified markers generated from a range of DNA samples isolated from tissue
      culture plants and pure isolates of B. pumilus-like bacteria.

PMID- 12789529
TI  - Impact of flumioxazin herbicide on growth and carbohydrate physiology in Vitis
      vinifera L.
AB  - The impact of flumioxazin herbicide on in vitro-grown grapevine ( Vitis vinifera
      L. cv. Chardonnay) was investigated. The herbicide treatments (1, 10 or 100 micro
      M flumioxazin in MM medium) had a negative impact on photosynthesis, as revealed
      by a reduction in foliar chlorophyll and carotenoid contents, gas exchanges and
      alteration in plastid structure and, consequently, resulted in a strong
      inhibition of plantlet growth. Surprisingly, soluble sugars and starch
      accumulated in all organs, suggesting a stimulation of sugar uptake from the
      medium. Moreover, photosynthetic activity and starch content partially recovered
      within 3 weeks of treatment at the weakest herbicide concentration. These results
      provide new insights into the physiological responses of non-target crops to
      flumioxazin, showing that flumioxazin is active in photosynthetic tissues of the
      non-target grapevine via root uptake, which is contrary to what is mentioned in
      the literature, and that the in vitro-grown plantlet is a good model for
      investigating the physiological effects of pesticides on crop species.

PMID- 12789530
TI  - Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen
      induced uveitis.
AB  - PURPOSE: Investigated the effect of N-3-aminomethylbenzylacetamidine (1400 W), a
      highly selective inhibitor of inducible nitric oxide synthase (iNOS), on the
      effector phase of EAU. METHODS: Sixteen Lewis rats were sensitized with bovine
      retinal S-antigen; ten of them injected subcutaneously with 1400 W (20 mg/kg)
      three times a day, from day 11 through day 13 following the injection of S
      antigen. Five of the ten rats were also injected intraperitoneally with
      polyethylene-glycol-modified superoxide dismutase (SOD 1000 IU) twice a day from
      day 7 through day 13. Six rats received intraperitoneal and/or subcutaneous
      injections of normal saline from day 7 through day 13. The eyes were enucleated
      on day 14. The intensity of the inflammatory lesion was assessed by a
      histological score. The thickness of the choroidal and photoreceptor layers was
      measured. RESULTS: The histological score was higher in the 1400 W-treated rats
      (26 +/- 2.1) than in the saline- (20.5 +/- 8; p < 0.0001) or 1400 W/SOD-treated
      rats (20.5 +/- 4.9; p < 0.005). The choroid was thicker in the 1400 W-treated
      rats (60.7 +/- 16.8 microm) than in the saline- (19.2 +/- 9.4 microm, p < 0.0005)
      or the 1400 W/SOD-treated rats (29.6 +/- 19.3 microm, p < 0.05). The
      photoreceptor layer was thinner in the 1400 W-treated rats (8.4 +/- 32.1 microm)
      than in the saline- (40 +/- 26.7 microm; p < 0.05) or 1400 W/SOD-treated rats
      (60.8 +/- 38.1 microm; p < 0.05). CONCLUSIONS: The data suggests that 1400 W
      exacerbates choroidal inflammation and photoreceptor damage at the effector phase
      of S-antigen-induced uveitis. This implies that iNOS expressed in the outer
      retina may have a protective role in EAU.

PMID- 12789531
TI  - Increased soluble interleukin-6 receptor in vitreous fluid of proliferative
      vitreoretinopathy.
AB  - PURPOSE: To clarify the effect of the interaction between interleukin-6 (IL-6)
      and its soluble receptor (sIL-6R) on retinal pigment epithelial (RPE) cell
      proliferation in proliferative vitreoretinopathy (PVR). METHODS: Concentrations
      of IL-6 and sIL-6R molecules in vitreous fluids were measured in eyes with PVR
      and idiopathic macular hole (MH), and the localization of IL-6 and IL-6R on the
      PVR fibrous membrane was studied. Production of IL-6 and sIL-6R by cultured RPE
      cells and the effect of the IL-6/sIL-6R complex on growth of cultured RPE cells
      were analyzed. RESULTS: Positive staining of IL-6 and IL-6R was observed in
      proliferating membranes in all PVR cases. IL-6 and sIL-6R concentrations in
      vitreous fluid from eyes with PVR were significantly higher than in eyes with MH
      (p < 0.05). A time-dependent increase in IL-6 molecules was identified in the
      culture medium of RPE cells, although sIL-6R was not detected. Dose-dependent
      growth of RPE cells was observed in the three concentrations (50, 100, and 500
      ng/ml) of sIL-6R used. CONCLUSION: IL-6 derived from blood during the breakdown
      of the blood-retinal barrier (BRB) and produced by RPE cells and hematogenous sIL
      6R cause RPE proliferation.

PMID- 12789532
TI  - Differential expression of the lenticular antioxidant system in laboratory
      animals: a determinant of species predilection to oxidative stress-induced ocular
      toxicity?
AB  - PURPOSE: Various animal species have been used to study oxidative stress-induced
      cataractogenesis; however, given that differences in the expression of the lens
      antioxidant system may influence species susceptibility to oxidative stress, we
      compared and contrasted a broad spectrum of components of the lens antioxidant
      system in dog, rat, marmoset, and rabbit. METHODS: Lenses collected from beagle
      dogs, Sprague-Dawley rats, marmosets, and New Zealand white rabbits were assayed
      for reduced glutathione (GSH), and activities of copper-zinc and manganese
      superoxide dismutase (CuZn-SOD; Mn-SOD), catalase (CAT), glutathione peroxidase
      (GPX), gamma-Glutamylcysteine synthetase (GCS), glutathione reductase (GR),
      glutathione-S-transferases (GST), and glucose-6-phosphate dehydrogenase (GPDH),
      and Trolox equivalent antioxidant capacity (TEAC). RESULTS: Expression of the
      lens antioxidant system varied considerably between species. Marmoset lens
      contained the highest levels of GSH, its respective biosynthetic and recycling
      enzymes GCS and GR, and the associated H(2 )O(2)-dismutation enzyme GPX.
      Activities of both SOD isoforms were also highest in marmoset lens. However,
      activities of the xenobiotic-conjugating enzyme GST and NADPH-generating enzyme
      GPDH were relatively low. In contrast, dog lens had the lowest levels of GSH,
      GCS, GR, and Cu-Zn SOD (1/2, 1/2 and 1/33, and 1/63 that in marmoset) but highest
      levels of GST and GPDH. Rabbit lens contained the highest CAT activity, at up to
      3.5-fold that for marmoset and rat. CONCLUSION: These results demonstrate
      substantial variation in lens antioxidant systems between different laboratory
      animal species. Given that such variation may affect relative susceptibility to
      oxidative stress-mediated ocular toxicity, our findings may provide useful
      information when choosing different animal species for lens research.

PMID- 12789533
TI  - Functional analysis of the human recoverin gene promoter.
AB  - PURPOSE: Following photoactivation of rhodopsin, recoverin inhibits rhodopsin
      kinase activity in retinal photoreceptors by reducing the binding of arrestin to
      rhodopsin and therefore prolonging the termination of the phototransduction
      cascade. To identify potential cis-elements that may be involved in understanding
      the mechanisms that determine the cell-specific expression of recoverin in
      retinal and cancerous cells, the promoter region of the human recoverin gene was
      studied in cultured human Y79 retinoblastoma cells. METHODS: A 2.5 kb EcoRI
      fragment of a 9.4 kb cosmid that contains the 5' non-coding region of the human
      recoverin gene was sequenced and cloned into an expression vector upstream of a
      luciferase gene. Cultured Y79 human retinoblastoma cells were transfected with
      DNA constructs using lipofection. Deletion mutants were generated by site
      directed mutagenesis, cloned into the expression vector, and transfected into Y79
      cells. Reporter gene activity was measured with a luciferase assay, and
      normalized to beta-beta-galactosidase activity resulting from a co-transfected SV
      beta-galactosidase SV40 vector. RESULTS: Reporter gene expression in the
      transfected Y79 cells demonstrated an increase in activity between 232 and 620 bp
      from the translational start site of the recoverin gene. There was a decrease in
      the reporter gene expression between 900 and 1200 bp from the start site,
      followed by an increase between 1200 and 1440 bp. CONCLUSIONS: This analysis
      suggests that there are cis-acting elements in the 5' non-coding region of the
      recoverin gene that are involved in the activation and suppression of gene
      expression.

PMID- 12789534
TI  - Molecular analysis of the pediatric ocular surface for fungi.
AB  - PURPOSE: To analyze the conjunctival flora of individuals 21 years of age or less
      for fungi using polymerase chain reaction (PCR) methodology. METHODS: Before
      povidone-iodine antisepsis, eye-swab specimens were collected from adolescent
      corneal donors preceding corneal excision and from children during preparation
      for strabismus surgery. Nucleic acid was extracted from the specimens and
      analyzed by PCR using primers designed for the detection of broad-spectrum fungal
      DNA and of Candida albicans-specific DNA. RESULTS: Twelve (38%) of 32 eye donor
      surfaces and 7 (23%) of 30 patient samples were positive for fungal DNA (P =
      0.1). C. albicans DNA was detected in 6 (19%) of the decedents' eyes but from
      none of the surgical patients (P = 0.04). CONCLUSIONS: Fungi were present on the
      normal ocular surface of children and adolescents. C. albicans was more likely to
      be found postmortem than pre-surgically.

PMID- 12789535
TI  - Suramin modulates wound healing of rabbit conjunctiva after trabeculectomy:
      comparison with mitomycin C.
AB  - PURPOSE: To investigate and compare the effects of suramin and mitomycin C on
      conjunctival wound healing after trabeculectomy in a rabbit model. MATERIALS AND
      METHODS: Thirty New Zealand White rabbits were divided into three groups, and
      trabeculectomy was performed on the left eyes under general anesthesia. During
      the surgery, suramin (250 mg/ml) and mitomycin C (0.4 mg/ml) were applied to the
      scleral flap site for 2 minutes in groups 1 and 2, respectively. The control
      animals (group 3) received no pharmacological treatment during trabeculectomy.
      Intraocular pressure (IOP) measurements were recorded before surgery and every 3
      days after the operation, starting from postoperative day 1. Three animals from
      each group were sacrificed on days 15, 20, and 25, yielding a total of 27 eyes
      for histopathological study. Each specimen was histochemically and
      immunohistochemically (CD3, CD20, CD68, and collagen III) evaluated, and graded.
      RESULTS: Bleb failure time was significantly longer in both the suramin (15.0 +/-
      4.7 days) and mitomycin C (16.7 +/- 5.1 days) groups than in the controls (10.3
      +/- 4.2 days) (p < 0.05). Starting from postoperative day 9, the IOP in the
      suramin and mitomycin C groups was significantly lower than that in the control
      group (p < 0.05). This difference continued to be significant until day 18 for
      the suramin group, and until day 24 in the mitomycin C group. Histopathological
      evaluation showed lower degrees of cellularity, fibrosis, collagen III
      deposition, and CD3 density in the suramin- and mitomycin C-treated eyes compared
      to control eyes at all time points (p < 0.05). There was also no significant
      difference between the suramin and mitomycin C groups concerning these
      histopathological findings and CD3 density (p > 0.05). Although there were trends
      towards reduced mean elastic fiber deposition and lower CD20 and CD68 density in
      both groups of treated eyes, the differences between the treated and control
      groups were not significant (p > 0.05). CONCLUSIONS: The results of the current
      study suggest that suramin has beneficial effects on wound healing in glaucoma
      surgery, and effectively prolongs bleb survival in rabbits. Suramin may be a
      promising alternative to anti-metabolite therapy in glaucoma surgery.

PMID- 12789536
TI  - Intravitreous anti-raf-1 kinase antisense oligonucleotide as an angioinhibitory
      agent in porcine preretinal neovascularization.
AB  - PURPOSE: To test the efficacy of a synthetic antisense oligonucleotide inhibitor
      of an intracellular signal transduction protein, C-raf-1 kinase, as an inhibitor
      of ocular neovascularization. METHODS: A 2'methoxyethyl, 2'deoxy chimeric 20
      nucleotide sequence containing a uniform phosphorothioate backbone was
      synthesized which targets the 3'untranslated region of porcine C-raf-1 mRNA (ISIS
      107189). Efficacy of mRNA inhibition was tested in vitro in porcine vascular
      endothelial cells and treated pigs by Northern blotting. In a pig model of
      intraocular neovascularization induced by branch retinal vein occlusion,
      intravitreal injection of ISIS 107189 compound (8 microM calculated intraocular
      concentration) at baseline and on days 14, 42, and 70, was tested against vehicle
      as control for inhibition of neovascularization. After enucleation on day 84,
      ocular tissues were analyzed for ISIS 107189 content by solid-phase extraction
      and capillary gel electrophoresis. Cryostat sections were immunostained for C-raf
      1 kinase protein. RESULTS: The antisense oligonucleotide demonstrated high
      potency for inhibition of C-raf-1 kinase in the porcine cells lines. Levels of C
      raf-1 kinase were also decreased in the retina of pigs following a single 180
      microg dose. Pig eyes injected with the multiple doses of 180 microg
      oligonucleotide demonstrated a marked decrease in neovascularization due to
      branch retinal vein occlusion 12 weeks after treatment (p = 0.05, Mann-Whitney U
      test). Posterior subcapsular cataracts were noted in the treated eyes.
      Concentrations of oligonucleotide in retina ranged from 2-12 microM in the
      treated eyes. Qualitative assessment of the expression of C-raf-1 kinase via
      immunohistostaining of frozen sections demonstrated inhibition of expression in
      the treated eyes compared to controls. CONCLUSIONS: ISIS 107189 successfully
      inhibited neovascularization in this model, which was correlated with an
      inhibition of expression of C-raf-1 kinase. While not proven in these studies,
      these results suggest that C-raf kinase may be important in angiogenesis.
      Antisense therapy has potential applicability in the therapy of ocular
      neovascular diseases.

PMID- 12789538
TI  - Glutamate receptors in the retina: the molecular substrate for visual signal
      processing.

PMID- 12789537
TI  - Intrinsic activation of PI3K/Akt signaling pathway and its neuroprotective effect
      against retinal injury.
AB  - PURPOSE: The aim of this study was to determine whether the phosphatidylinositol
      3-kinase (PI3K)/Akt signaling pathway can function as a neuroprotective pathway
      following induced retinal injury. METHODS: The activation of Akt was assessed by
      immunoblot analysis, and the role of PI3K/Akt pathway was evaluated by TUNEL
      staining and counting the number of retrogradely-labeled retinal ganglion cells
      (RGCs) in the whole retina at 168 h after injury with or without PI3K specific
      inhibitor, LY294002. RESULTS: Akt was induced within one hr and reached a maximum
      6 hrs after optic nerve clamping. The activation was observed in the RGC layer
      including RGCs, the inner plexiform layer, inner nuclear layer, and in the
      photoreceptor outer segments. The number of surviving RGCs was decreased
      significantly 168 hrs after injury. LY294002 partially inhibited the activation
      of Akt, and significantly decreased the number of surviving RGCs as compared with
      that of injury alone. CONCLUSIONS: These results indicate that the PI3K/Akt
      signaling pathway is activated intrinsically and has a neuroprotective effect on
      injured RGCs.

PMID- 12789539
TI  - RGD peptide-assisted vitrectomy to facilitate induction of a posterior vitreous
      detachment: a new principle in pharmacological vitreolysis.
AB  - PURPOSE: To evaluate a new concept in pharmacological vitreolysis by studying the
      efficacy of intravitreal RGD peptide-assisted vitrectomy in facilitating the
      separation of the posterior cortical vitreous from the retinal surface in an
      animal model. METHODS: Eight rabbits (16 eyes) received an intravitreal injection
      of 1 or 5 mg of RGD peptide in one eye and either RGE peptide (inactive control)
      or phosphate buffered saline in the fellow eye. After 24 hours, a pars plana
      vitrectomy with low aspiration (< or =30 mmHg) was performed in an attempt to
      create a detachment of the posterior cortical vitreous. A masked observer
      performed pre- and postoperative indirect ophthalmoscopy and B-scan
      ultrasonography. Postoperative scanning electron microscopy evaluated the
      vitreoretinal surface in selected eyes. Two additional rabbits received
      intravitreal injections of RGD peptide in one eye (1 mg and 5 mg) and 1 mg of RGE
      peptide in the fellow eye to examine apoptosis of the retinal cells by TUNEL
      assay. RESULTS: Based on postoperative ultrasound findings, six of the eight
      rabbits had a greater degree of posterior vitreous detachment in the RGD eye
      compared to the fellow eye (p = 0.03). The total number and the average number of
      detached quadrants in the group of RGD peptide eyes was twenty-three and 2.85
      respectively compared to seven and 0.85 for the control fellow eyes (p = 0.02).
      Scanning electron microscopy confirmed the presence of postoperative posterior
      vitreous detachment. There was no evidence of retinal cell apoptosis in RGD
      injected eyes. CONCLUSION: RGD peptide-assisted vitrectomy facilitated posterior
      vitreous detachment in rabbit eyes, suggesting that RGD-containing peptides may
      prove to be effective adjuncts in producing posterior vitreous separation during
      vitreous surgery.

PMID- 12789540
TI  - Calculation of the diameter of the central retinal artery from noninvasive
      measurements in humans.
AB  - PURPOSE: The aim of the present study was to calculate the diameter of the
      central retinal artery from results as obtained with non-invasive techniques in
      healthy young subjects. METHODS: Twenty-four healthy male subjects participated
      in this study. Total retinal blood flow was calculated from combined bi
      directional laser Doppler velocimetry and measurement of retinal venous diameters
      using the Zeiss retinal vessel analyzer. Using these techniques red blood cell
      velocity and vessel diameters of all visible veins entering the optic nerve head
      were measured and total retinal blood flow was calculated. Blood flow velocity in
      the central retinal artery was measured with color Doppler imaging. Form these
      outcome parameters the diameter of the central retinal artery was calculated for
      each subject individually. RESULTS: In the present study cohort the mean retinal
      blood flow was 38.1 +/- 9.1 microl/min and the mean flow velocity in the central
      retinal artery was 6.3 +/- 1.2 cm/s. From these data we calculated a mean
      diameter of the central retinal artery of 163 +/- 17 microm. CONCLUSIONS: Our
      results are in good agreement with data obtained from in vitro studies. The data
      of the present study also indicate that one needs to be careful to interpret
      velocity data from the central retinal artery in terms of retinal blood flow.

PMID- 12789542
TI  - Dual-directional optokinetic nystagmus elicited by the intermittent display of
      gratings in primary open-angle glaucoma and normal eyes.
AB  - PURPOSE: To compare optokinetic nystagmus (OKN) responses to the intermittent
      display of stimuli between normal subjects and patients with primary open-angle
      glaucoma (POAG). METHODS: Optokinetic nystagmus (OKN) was recorded in 9
      glaucomatous patients and 7 normal subjects. The computer-generated stimuli
      displayed sinusoidal luminance gratings (16 cd/m(2) mean luminance, 0.5 cyc/deg)
      with a pi/2 phase shift between successive stimulus gratings. These stimulus
      gratings were separated by an interstimulus interval (ISI), during which a
      homogeneous luminance field of 16 cd/m(2) was presented. The ISI duration and the
      luminance contrast were set at different values. RESULTS: For normal subjects,
      dual-directional alternating OKN could be evoked in the ISI range from 33 to 100
      ms. The dual-directional alternating OKN was defined as that OKN slow phase
      alternatively tracked in the direction of pi/2 shift (forward OKN) and against
      the pi/2 shift (reverse OKN). By contrast, for most glaucomatous eyes, nearly no
      reverse OKN could be evoked at any ISI value. CONCLUSIONS: The lack of reverse
      OKN in POAG patients in the present experiments is a meaningful finding. The
      occurrence of reverse OKN during a certain range of ISI duration could be related
      to the biphasic characteristics of the temporal impulse response in normal
      subjects, whereas, the lack of reverse OKN might suggest the plausible damage of
      magnocellular cells in POAG.

PMID- 12789543
TI  - Chemotactic and chemokinetic properties of topical ophthalmic preparations.
AB  - PURPOSE: Chronic ocular inflammation can be due to a disease process or to
      iatrogenic factors that attract inflammatory cells to the anterior chamber. This
      study was conducted to investigate the effect of commonly used ophthalmic
      preparations on leukocyte migration. METHODS: A modified multi-well Boyden
      chamber was used to study the chemotactic and chemokinetic effects of 33
      commercial ophthalmic preparations. To determine whether the chemotactic effect
      was a property of the commercial ophthalmic preparation or other chemicals
      present in the products, experiments were also done with some common
      preservatives and excipients. RESULTS: Of the drugs, 14 (42.4%) showed
      chemokinetic and/or chemotactic activity and 19 (57.6%) had either no effect or
      decreased neutrophil migration. Of the preservatives and excipients, 5 (62.5%)
      were found to be chemotactic. Eleven of 14 chemotactic drugs (78.6%) and 8 of 19
      non-chemotactic drugs (42.1%) were positive for at least one chemotactic
      excipient. The correlation between chemotactic ophthalmic preparations and the
      presence of a chemotactic excipient in their composition was significant (p <
      0.05). CONCLUSIONS: Chemotactic activity was commonly found in commercial
      ophthalmic preparation. Furthermore, the presence of certain chemotactic
      preservatives and/or excipients was a contributing factor enhancing this
      property. Avoiding known chemotactic compounds or adjusting the intervals of the
      treatment may help to eliminate this iatrogenic component of the inflammatory
      process especially in patients with chronic ocular inflammation.

PMID- 12789541
TI  - Transformation of human trabecular meshwork cells with SV40 TAg alters promoter
      utilization.
AB  - PURPOSE: To compare promoter usage in primary differentiated and SV40 TAg
      transformed human trabecular meshwork cells (HTM and TM1 cells). METHODS:
      Cultured HTM and TM1 cells were transfected with vectors expressing MYOC/TIGR
      from the CMV-IE, IE4/5 (HSV immediate early 4/5), ICP6 (early gene ICP6 of HSV),
      EF-1 alpha (human elongation factor 1 alpha-subunit), or the UB6 (human
      ubiquitin) promoters, respectively. Immunoblotting was used to measure MYOC/TIGR
      protein expression. MYOC/TIGR expression at the RNA level was detected by
      Northern blotting. RESULTS: In primary HTM cells, CMV was the only promoter
      displaying substantial activity. In TM1 cells, several promoters were functional
      with the order in decreasing activity being EF-1 alpha > or = CMV > or = UB6 >>
      IE4/5. CONCLUSIONS: The difference between the normal and transformed HTM cells
      suggests that the latter cell type has alterations that influence cellular
      promoter function. The type of cell used is likely to be a crucial factor in
      evaluating the functions of promoter elements for genes expressed in the
      trabecular meshwork and in screening promoters for use in gene delivery studies,
      especially for evaluations of the MYOC/TIGR gene in relation to glaucoma
      mechanisms.

PMID- 12789544
TI  - The correlation among different immunostaining evaluation methods for the
      assessment of proliferative activity in uveal melanoma.
AB  - PURPOSE: Proliferative index of uveal melanoma cells serves as a prognostic
      factor. However, different methods are being used to determine proliferative
      index using immunostaining for proliferative markers. The major differences among
      assessment methods are whether the mean proliferative activity of all tumor cells
      in a section or for areas of rapidly proliferating cells is determined, and
      whether 10 or 20 fields are being evaluated. We aimed to assess the correlation
      among proliferative indexes obtained by different immunostaining evaluation
      methods. METHODS: Sections from 60 formalin-fixed paraffin-embedded uveal
      melanomas were immunostained with MIB-1 antibody. Immunostaining was assessed by
      counting immunoreactive cells in semi-randomly selected fields (non-selective
      method) and in areas with maximal immunoreactivity (selective method).
      Proliferative activity indexes according to the two methods in 10 and 20 high
      power fields (one high power filed = 0.785 mm(2)) were calculated and compared.
      RESULTS: The mean positive cell counts per mm(2) (MPCC/mm( 2)) according to the
      selective and the non-selective methods were 29.8 +/- 8.1 and 10.7 +/- 2.4
      respectively (p = 0.004, paired t-test). Despite these different values, there
      was a good correlation between the MPCC/mm( 2) obtained by the non-selective and
      the selective methods for each tumor (r = 0.737, p < 0.0001, Pearson
      correlation). In addition, according to both methods, the readings of the first
      10 fields and those of fields 1-20 correlated well. CONCLUSIONS: Mean
      proliferative activity of uveal melanoma cells correlates with the proliferative
      activity in localized areas of the tumor with rapidly proliferating cells.
      Therefore, uveal melanomas are classified similarly by the selective and non
      selective methods of immunostaining evaluation. However, the two methods yield
      different proliferative index values for the same tumors, a fact that should be
      taken into account when comparing results of studies in which different
      techniques were used for immunostaining evaluation.

PMID- 12789545
TI  - Morphologic characteristics of retinal degeneration induced by sodium iodate in
      mice.
AB  - PURPOSE: Retinal degeneration induced by sodium iodate (NaIO( 3)) in mice was
      evaluated morphologically. METHODS: Male and female ICR and C57BL mice were
      intraperitoneally administered 100 mg/kg NaIO(3) at 7 weeks of age, and were
      killed 6, 12, 24 hrs, and 3, 7 and 28 days after the treatment. Retinas were
      examined histologically, ultrastructurally, immunohistochemically, and by the
      TUNEL method. RESULTS: Retinal degeneration was evoked in all NaIO(3)-treated
      mice. The primary site of damage appeared in the retinal pigment epithelial (RPE)
      cells followed by photoreceptor cell degeneration. Initially, the RPE cells
      showed necrosis starting 6 hrs post-NaIO(3), followed by photoreceptor outer
      segment disruption and photoreceptor cell apoptosis at 24 hrs; photoreceptor cell
      apoptosis peaked at day 3 and was completed by day 7. At day 3, Muller cell
      proliferation, macrophage migration within the retina, and regeneration of
      damaged RPE cells occurred. Finally at day 7 and day 28, the retina showed a
      mosaic pattern of relatively normal retina and areas lacking RPE cells and
      photoreceptor cells. CONCLUSIONS: RPE cell necrosis followed by photoreceptor
      cell apoptosis and the resulting mosaic pattern of the retina phenotypically
      resembles gyrate atrophy of the choroid and retina.

PMID- 12789546
TI  - Upregulation of glucose-dependent insulinotropic polypeptide and its receptor in
      the retina of streptozotocin-induced diabetic rats.
AB  - The pathology of diabetic retinopathy includes dilatation and beading of retinal
      vessels, and vascular sheathing. To gain a better understanding of the molecular
      events leading to diabetic retinopathy, we investigated disease-specific gene
      responses by screening differential expression using cDNA microarray. Male
      Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ, 50
      mg/kg) or the control buffer and were maintained for 6 weeks. Total RNA extracted
      from the retinas of both groups was used for cDNA microarray analysis. Signals
      from all the spots representing hybridized DNA were quantified and compared
      between the normal and diabetic rat retinas. Among 1176 genes analyzed, the
      retinal expression of glucose-dependent insulinotropic polypeptide (GIP) was
      found to increase in STZ-induced diabetic rats compared to controls. GIP is a
      secreted protein, known to be released from the small intestine, which
      potentiates glucose-induced insulin secretion from the pancreas. However, the
      expression of GIP and its receptor (GIPR) has not been previously noted in the
      rat retina. To further validate the expression of GIP in the rat retina and to
      determine its possible role in the development of early diabetic retinopathy, we
      investigated its expression by RT-PCR, Northern blotting, and
      immunohistochemistry in normal and diabetic rat retinas. GIP mRNA and protein are
      not only expressed in the rat retina, but their levels are greater in the
      diabetic rat as compared to controls. And GIPR expression was also upregulated in
      the retinas of STZ-induced diabetic rats. We here demonstrate for the first time
      the expression of GIP and GIPR in the rat retina. And we also revealed some
      genetic events in the early stage of diabetic retinopathy including the de novo
      increment of GIP and GIPR expression in the retina.

PMID- 12789547
TI  - Activation of caspase 9 in a rat model of experimental glaucoma.
AB  - PURPOSE: We investigated retinal ganglion cell (RGC) death and activation of
      caspase 9 in rats with experimental glaucoma. METHODS: Elevated intraocular
      pressure (IOP) was induced in rats using the Morrison model. Surviving
      backlabeled RGC were counted and TUNEL staining detected apoptosis. Procaspase 9
      expression and activated caspase 9 were studied by immunoblot and
      immunohistochemistry. RESULTS: IOP correlated with surviving RGC. TUNEL-positive
      RGC were observed in animals with elevated IOP. Procaspase 9 levels increased
      with IOP intensity. Cleaved caspase 9 was detected by immunoblot only in rats
      with peak IOP above 35 mm Hg for > or =6 days. Cleaved caspase 9 staining was
      seen only in the ganglion cell layer of retinas from rats with peak IOP > or =32
      mm Hg. CONCLUSIONS: RGC loss is correlated with IOP in experimental glaucoma.
      These results support activation of caspase 9, the intrinsic caspase cascade, in
      RGC death in experimental glaucoma.

PMID- 12789570
TI  - Duke University honors Gordon Klintworth.

PMID- 12789571
TI  - The gene for Stargardt disease, ABCA4, is a major retinal gene: a mini-review.
AB  - The gene ABCA4 encodes the rod and cone photoreceptor Rim protein, which is a
      transmembrane transporter of vitamin A intermediates. ABCA 4 mutations are
      responsible for a large variety of retinal degenerations including all cases of
      Stargardt macular dystrophy and fundus flavimaculatus, some forms of cone-rod
      degeneration, and retinitis pigmentosa, and likely increase the risk of
      developing age-related macular degeneration (AMD). The purpose of this mini
      review is to highlight the advances in our understanding of Stargardt disease and
      the ABCA4 gene from the first description of the disease by Karl Stargardt in
      1909 to gene discovery by Allikmets and colleagues in 1997. The knockout mouse
      model by Mata and co-workers has provided crucial pathophysiological information
      that has led to new ideas regarding treatment possibilities. These hypotheses
      were tested by Radu and colleagues in the mouse and shown to be efficacious.

PMID- 12789572
TI  - Ophthalmic manifestations of congenital disorder of glycosylation type 1a.
AB  - PURPOSE: To present the ophthalmic manifestations of patients with congenital
      disorder of glycosylation type Ia (CDG-Ia) due to the frequent R141H/F119L PMM2
      genotype. METHODS: Ophthalmic records of 23 patients (age: 10 months to 20 years)
      were evaluated. They had had at least one ophthalmic reexamination. RESULTS:
      Measurements of refractive error showed that 18 patients were myopic, two were
      hypermetropic, and three could not be measured. Serial measurements in 12
      patients indicated a progression towards myopia of 0.80 diopters (D) per year.
      Congenital esotropia and delayed visual maturation (DVM) were consistent
      findings. Two children developed good visual acuity (VA), 16 had low vision, and
      five were legally blind. Pallor of the optic disc was noted in five patients.
      Electroretinography (ERG) performed in nine patients showed reduced rod
      responses, while cone responses were only slightly reduced. CONCLUSIONS: The
      present study illustrates the difficulties in examining severely disabled
      children. Consistent ophthalmic manifestations of CDG-Ia patients due to the
      R141H/F119L genotype were congenital esotropia, DVM, and a reduced rod response
      in ERG-examined patients. The vast majority of patients had reduced VA and
      developed myopia. We speculate that there is a relationship between the
      glycosylation defect in CDG-Ia and the development of myopia. We recommend that
      CDG-Ia patients be followed annually by an ophthalmologist.

PMID- 12789573
TI  - Phenotype in two families with RP3 associated with RPGR mutations.
AB  - OBJECTIVE: To describe the phenotype of three patients and two carriers from two
      families with mutations in the RPGR gene. The genotypes (a 75-kb deletion on the
      X chromosome spanning the RPGR gene and the first exon of the SRPX gene, and a
      stop mutation (G52X) in the RPGR gene) have been reported previously. METHODS: A
      clinical examination including Goldmann perimetry, full-field electroretinography
      (ERG), dark adaptometry, and dark- and light-adapted two-color threshold (500-nm
      cut-off, 600-nm cut-on filter) perimetry was performed in all patients and one
      carrier. The second carrier was only examined clinically. RESULTS: All affected
      males presented with a marked decrease in visual acuity of 0.3 to 0.5 at the age
      of 17-22.5 years, and a typical fundus appearance. The stop mutation (G52X)
      appeared to be associated with a more pronounced bone spicule formation compared
      to the deletion of the entire RPR gene and the first exon of the SRPX gene. The
      kinetic visual fields were constricted to < 20 degrees eccentricity, in part with
      a residual island in the temporal field. Using two-color dark-adapted threshold
      perimetry, rod function was more reduced than cone function. The ERG was
      extinguished. The carrier with the stop mutation showed sectorial peripheral bone
      spicules and ERG changes typical of carriers of XLRP. The carrier with the
      deletion had no visual complaints, full visual acuity, and only minimal
      peripheral retinal changes. Goldmann perimetry showed minor peripheral defects
      with small targets. ERG amplitudes were reduced below the 10th percentile of
      normals, without selective loss in rods or cones. The scotopic (rod) sensitivity
      loss at 500 nm was more pronounced than the photopic (cone) sensitivity loss at
      600 nm. Neither of the two carriers showed a tapetal reflex. CONCLUSION: The
      affected males of the two families with RPGR mutations already exhibited
      retinitis pigmentosa with severe impairment of the rod and cone system during
      their second decade of life. The degree of bone spicules differed between the two
      families. Psychophysics detected a slightly more pronounced affection of the rod
      system compared to the cone system in both the hemizygous males and the carrier
      with the deletion of the RPGR gene and the first exon of the SRPX gene.
      Psychophysics disclosed mild progression of the disease in the carrier
      underlining the potential of the method in monitoring the disease course. As in
      most other reported phenotypes of RPGR mutations, no tapetal reflex was found in
      the carriers.

PMID- 12789574
TI  - Allelic variants in the MYOC/TIGR gene in patients with primary open-angle,
      exfoliative glaucoma and unaffected controls.
AB  - One of the leading causes of blindness in the world is glaucoma. The most common
      form is primary open-angle glaucoma (POAG). The only gene identified so far as
      being associated with POAG is the MYOC gene; 2-4% of the patients have been
      reported to carry mutations in this gene. Exfoliative glaucoma is a secondary
      glaucoma, in which one of the symptoms is exfoliations on the lens capsule and
      anterior segment of the eye. No gene has been identified as being associated with
      this variant. The aim of the present study was to analyze Swedish patient
      material for allelic variants and mutations in the coding region of the MYOC
      gene. Two hundred patients with POAG and 200 with exfoliative glaucoma were
      analyzed using enzymatic cleavage assay and denaturing high-performance liquid
      chromatography (dHPLC). An age-matched control group (n = 200), in whom glaucoma
      had been excluded, was also analyzed using dHPLC. Eight allele variants were
      identified, two of which were determined to be disease-causing mutations. These
      two disease-causing mutations were only found in POAG patients, indicating a
      prevalence of 1% in this patient group. This frequency is lower than that
      reported in other studies of other populations. No disease-causing mutations were
      found in the exfoliative glaucoma patients, indicating a fundamentally different
      genetic basis for that glaucoma variant.

PMID- 12789576
TI  - Congenital cystic eye: recurrence after initial surgical removal.
AB  - Congenital cystic eye arises from failure of invagination of the primary optic
      vesicle. The cyst lacks the usual intraocular structures and contains only
      abortive derivatives of the anterior and posterior portions of the primary optic
      vesicle. Because the cystic eye usually occupies a large portion of the orbit and
      distends the upper eyelid, surgical excision is often carried out. We report a
      case of congenital cystic eye in which an initial attempt at excision was
      followed in three months by recurrence of the cyst in the orbit. A second
      excision appears to have eliminated the cyst since no recurrence has become
      evident in the ensuing two years. The pathology of the cyst from both excision
      specimens suggests that the pigmented cells from the posterior portion of the
      cyst were not included in the first resection. Based on this experience, we
      conclude that every effort should be made to excise all of the congenital cystic
      eye when surgical removal is undertaken.

PMID- 12789575
TI  - A novel syndrome of congenital lid and punctal anomalies, corneal and
      chorioretinal dystrophy.
AB  - A 28-year old woman had an ocular syndrome consisting of congenital lid and
      punctal anomalies, and corneal and chorioretinal dystrophy without facial
      dysmorphism. These combined malformations of the ocular adnexae and both anterior
      and posterior ocular segments have not been previously described and appear to
      represent a novel syndrome. Direct sequencing of PAX6 and the DNA-binding domain
      of FOXC1 failed to detect a mutation.

PMID- 12789577
TI  - Abnormal retinal architecture in a 33-week-old fetus with LCA and a homozygous
      C330Y mutation in RPE65.

PMID- 12789578
TI  - The major gene for Bardet-Biedl syndrome is BBS1.

PMID- 12789579
TI  - Thickness of the retinal nerve fiber layer in patients with anisometropic and
      strabismic amblyopia.
AB  - PURPOSE: To compare the retinal nerve fiber layer [RNFL] thickness of the
      amblyopic eye with that of the normal eye in patients with anisometropic and
      strabismic amblyopia. METHODS: Scanning laser polarimetry was performed with the
      GDx Nerve Fiber Analyzer (NFA), a scanning laser ophthalmoscope that measures the
      thickness of the peripapillary RNFL quantitatively and objectively, in vivo,
      based on the birefringence of the RNFL. Eighteen anisometropic, two strabismic
      and four combined amblyopic (both anisometropia and strabismus) patients were
      enrolled in the study. There were 9 male and 15 female patients, age range 7-66
      years. Using Student's t-test, 14 GDx parameters in the amblyopic eyes and sound
      eyes were compared. RESULTS: The GDx parameters showed no significant differences
      between the two groups [p > 0.5]. The superior average and inferior average
      values were 79.50 microm and 80.41 microm, respectively, in the amblyopic group,
      and 80.75 microm and 82.75 microm, respectively, in the healthy eyes. The average
      thickness did not differ between amblyopic and sound eyes (65.50 microm and 66.45
      microm, respectively). CONCLUSION: Assessment of RNFL thickness by means of
      scanning laser polarimetry revealed no difference between the two eyes in
      patients with unilateral amblyopia.

PMID- 12789580
TI  - Influence of eye position on stereo matching.
AB  - In animals with binocular depth vision, or stereopsis, the visual fields of the
      two eyes overlap, shrinking the overall field of view. Eye movements increase the
      field of view, but they also complicate the first stage of stereopsis: the search
      for corresponding images on the two retinas. If the eyes were stationary in the
      head, corresponding images would always lie on retina-fixed bands called epipolar
      lines. Because the eyes rotate, the epipolar lines move on the retinas.
      Therefore, the stereoptic system has a choice: it may monitor eye position to
      keep track of the epipolar lines, or it may give up on tracking epipolar lines
      and instead search for matches over retina-fixed regions, but in that case the
      search regions must be 2-D patches, large enough to encompass all possible
      locations of the epipolar lines in all usual eye positions. We use a new type of
      random-dot stereogram to show that human stereopsis uses large, retina-fixed
      search zones. We show that the brain somewhat reduces the size of these search
      zones by rotating the eyes about their lines of sight in a way that reduces the
      motion of the epipolar lines. These findings show the link between sensory and
      motor processes: by considering eye motion we can understand why the brain
      searches for matching images over 2-D retinal regions rather than along epipolar
      lines; and by considering retinal correspondence we appreciate why the eyes
      rotate as they do about their lines of sight.

PMID- 12789581
TI  - Dynamic eye plant models and the control of eye movements.
AB  - Models of the oculomotor plant (globe, muscles, pulleys, and orbital tissues)
      fall into three categories: 1). one-dimensional dynamic with lumped plant
      elements, 2). three-dimensional dynamic with lumped plant elements, or 3). three
      dimensional static with distinct plant elements. The second class of models is
      most often used when studying the neural control of 3-D eye movement, because
      they best represent the plant dynamics. However, they are often faulted because
      they make two unrealistic assumptions: 1). muscle pairs act along the three
      orthogonal axes (symmetry assumption); and 2). the force generated by the muscles
      depends only on their innervation (force assumption). It turns out that the
      symmetry assumption is quite benign, because in a realistic model of the plant
      the deviations from orthogonal axes can be easily accounted for by simple
      adjustments to the innervation. In contrast, the force assumption introduces some
      serious problems. In the present paper, the authors show that a realistic,
      dynamic model of the geometry of the orbit, with independent muscles, makes
      different predictions than a similar model with lumped muscles. This difference
      arises because muscle force is a function of both innervation and muscle length.

PMID- 12789582
TI  - Ocular kinematics and eye-hand coordination.
AB  - Eye-hand coordination is complicated by the fact that the eyes are constantly in
      motion relative to the head. This poses problems in interpreting the spatial
      information gathered from the retinas and using this to guide hand motion. In
      particular, eye-centered visual information must somehow be spatially updated
      across eye movements to be useful for future actions, and these representations
      must then be transformed into commands appropriate for arm motion. In this
      review, we present evidence that early visuomotor representations for arm
      movement are remapped relative to the gaze direction during each saccade. We find
      that this mechanism holds for targets in both far and near visual space. We then
      show how the brain incorporates the three-dimensional, rotary geometry of the
      eyes when interpreting retinal images and transforming these into commands for
      arm movement. Next, we explore the possibility that hand-eye alignment is
      optimized for the eye with the best field of view. Finally, we describe how head
      orientation influences the linkage between oculocentric visual frames and
      bodycentric motor frames. These findings are framed in terms of our 'conversion
      on-demand' model, in which only those representations selected for action are put
      through the complex visuomotor transformations required for interaction with
      objects in personal space, thus providing a virtual on-line map of visuomotor
      space.

PMID- 12789583
TI  - Ocular kinematics, vergence, and orbital mechanics.
AB  - Important aspects of ocular kinematics relate to the geometric configuration of
      extraocular muscles (EOMs). The orbital layer of each rectus EOM inserts on a
      connective tissue ring called a pulley that deflects the EOM path. Global layer
      fibers of each EOM pass through the pulley to insert on the sclera. The orbital
      layer thus controls linear translation of the pulley, regulating the EOM's
      pulling direction, while the global layer rotates the eye. The active pulley
      hypothesis (APH) states that pulleys are actively positioned to regulate ocular
      kinematics. The coordinated control postulate of the APH proposes that during
      conjugate visually guided eye movements, rectus pulleys move the same
      anteroposterior distance as their insertions, but the inferior oblique pulley
      moves with vertical gaze by half the amount as the inferior rectus insertion.
      These motions, observable by magnetic resonance imaging (MRI), shift the pulling
      directions of these EOMs by half the ocular angle, mechanically implementing a
      'linear oculomotor plant' appearing mathematically commutative to the brain and
      consistent with Listing's Law of ocular torsion. In the non-converged state with
      the head upright and stationary, rectus pulleys move little transverse to the EOM
      axes. During convergence and during the static torsional vestibulo-ocular reflex,
      MRI shows that the rectus pulley array rotates around the line of sight. Oblique
      EOM orbital layers may implement this shift.

PMID- 12789584
TI  - First description of eye muscle 'poulies' by Tenon in 1805.

PMID- 12789585
TI  - Anatomical observations on some parts of the eye and eyelids. 1805.

PMID- 12789587
TI  - Orbital vascular anatomy and vascular lesions.

PMID- 12789588
TI  - Microanatomy of the blood supply to the optic nerve.
AB  - The vascularization to the optic nerve is understood to come from the superior
      hypophyseal arteries and ophthalmic artery. However, anatomical studies about
      their detailed distribution to the optic nerve, especially its intracanalicular
      part, are rare. As the optic nerve is very prone to compression inside the optic
      canal, the vascularization here is especially at risk. This study shows that the
      superior hypophyseal arteries are the main source of blood supply to the
      intracranial and intracanalicular part of the optic nerve. The contribution of
      the ophthalmic artery to this part of the nerve is negligible. This artery mainly
      contributes to the intraorbital part of the optic nerve by means of the short and
      long ciliary arteries and the central retinal artery.

PMID- 12789589
TI  - Cerebrofacial vascular disease.

PMID- 12789590
TI  - Vascular malformations of the orbit: hemodynamic concepts.
AB  - Vascular malformations of the orbit can best be understood within the context of
      their hemodynamics, of which there are three types. Type 1 (no flow) lesions have
      essentially little connection to the vascular system and include lymphangiomas or
      combined venous lymphatic malformations. Type 2 (venous flow) lesions appear as
      either distensible lesions with a direct and rich communication with the venous
      system or nondistensible anomalies that have minimal communication with the
      venous system. Types 1 and 2 can be combined with both features of distensible
      and nondistensible hemodynamics. Arterial flow lesions, type 3, include
      arteriovenous malformations characterized by direct antigrade high flow through
      the lesion to the venous side. Cavernous hemangiomas are also malformations that
      demonstrate direct low flow through the lesion.

PMID- 12789591
TI  - Carotid-cavernous and orbital arteriovenous fistulas: ocular features, diagnostic
      and hemodynamic considerations in relation to visual impairment and morbidity.
AB  - The author investigated 101 cases with direct dural carotid-cavernous and orbital
      arteriovenous fistulas (CCF). The characteristic clinical findings, such as
      specific epibulbar arterialized loops, are described and the differential
      diagnosis of the striking diagnostic triad (exophthalmos, the above-mentioned
      loops and glaucoma) is discussed, together with the exclusion criteria for other
      causes of red eyes, episcleral measurements and blood flow. The results of
      various diagnostic procedures, such as ultrasonography, Doppler hematotachography
      and color Doppler of the orbit and carotid systems, magnetic resonance imaging
      and angiography, and of conservative treatment and embolization processes are
      dealt with successively. The classification of different types of carotid
      cavernous fistulas is presented,(1-3) together with the clinical signs in
      relation to morbidity and mortality during or after conservative or intervention
      therapies. The importance of patient follow-up, in the clinic as well as with
      Doppler methods, is emphasized in order to differentiate a progressive or
      diminished clinical condition caused by spontaneous thrombosis in the healing
      process or more arteriovenous flow. A 'decision tree' for use in daily practice
      is provided. In this study, of the 101 cases in which the localization was
      diagnosed by angiography, 42 were direct (30 traumatic, 12 spontaneous), 31 were
      dural (3 traumatic, 28 spontaneous) and 10 were orbital CCFs. In 18 other cases,
      usually dural or orbital shunts, angiography was not performed. For the
      management of 42 direct fistulas, conservative treatment was used in 12 cases (7
      with success; 58%) and balloon embolization was performed in 18 cases (17 with
      success; 94.5%); the other cases were treated by direct or indirect surgery. Of
      the 48 (spontaneous and traumatic) dural fistulas, 39 were treated conservatively
      (32 recovered or were much improved: 82%, of the total cases, 67%). All seven
      cases in which embolization was performed were cured and/or much improved. In two
      cases, one fistula was conservatively treated while one was embolized at another
      location, both with success. Of the 10 orbital arteriovenous shunts showing signs
      of dural fistulas, the features disappeared in 8 cases, although after a much
      longer follow-up period than for the typical dural carotid-cavernous sinus
      fistulas; in one patient, direct surgery was performed successfully and in one
      patient the original, non-progressive, orbital features could still be observed.

PMID- 12789592
TI  - An old crone finds a new home: Crohn's disease and pars planitis.

PMID- 12789593
TI  - Optic neuritis in multiple sclerosis.
AB  - PURPOSE: To review the clinical features, natural history, potential pathogenic
      mechanisms, differential diagnosis, and management of optic neuritis in multiple
      sclerosis. METHODS: Relevant literature regarding optic neuritis in multiple
      sclerosis from 1970 to the present was reviewed. RESULTS: Optic neuritis is an
      acute inflammatory optic neuropathy. It is the most common type of optic
      neuropathy causing acute visual loss in young adults (peak age at 30-40 years),
      especially among women. Patients usually present with an acute reduction of
      visual acuity, orbital pain exacerbated by eye movements, dyschromatopsia, and an
      afferent papillary defect, with or without swelling of the optic nerve head.
      Visual field testing most often reveals central defects, but others, such as
      centrocecal, can also occur. Magnetic resonance image (MRI) scanning of the brain
      should be undertaken in all cases of acute optic neuritis for diagnostic and
      prognostic purposes. The brain lesions of multiple sclerosis are commonly seen as
      T2 ovoid high-signal white matter lesions on MRI scans of the brain located in
      perivenular regions perpendicular to ventricles with variable enhancement. For
      atypical presentations of optic neuritis, additional laboratory tests, such as
      cerebrospinal fluid analysis, serologic tests, and visual evoked potentials,
      prove to be useful in the diagnosis and subsequent management of the patient. The
      recommended treatment for optic neuritis is intravenous steroids, as shown in the
      Optic Neuritis Treatment Trial (ONTT). CONCLUSION: Optic neuritis is often the
      initial presentation of multiple sclerosis. Recent advances in the understanding
      of the immune basis for multiple sclerosis has led to earlier and more effective
      treatment of this disease.

PMID- 12789594
TI  - Blood-aqueous barrier in prostaglandin EP2 receptor knockout mice.
AB  - The role of prostaglandin EP(2) receptors in the disruption of the blood-aqueous
      barrier was examined using EP(2) receptor-deficient mice. Eyes were topically
      treated with EP receptor agonists or subjected to paracentesis. Fluorescein
      angiography was performed after topical treatment with 2.0 icrog butaprost. The
      results show that EP receptor agonists, PGE( 2) and the EP(2) receptor-selective
      agonist butaprost, increased aqueous humor protein in EP(2) +/+ wild-type mice to
      18.0 mg/ml and 12.0 mg/ml, respectively, from the control value of 2.7 mg/ml. The
      increase in aqueous humor protein concentration in response to these EP receptor
      agonists was reduced significantly in EP(2) receptor-deficient mice. Fluorescein
      leakage into the anterior chamber, two minutes after its injection, was
      significantly greater in butaprost-treated wild-type mice than in butaprost
      treated knockout mice. Protein concentration, 15 min after paracentesis,
      increased from 2.2 mg/ml to 25.0 mg/ml in the aqueous humor of the eyes of wild
      type mice, while the increase in knockout mice was 10.6 mg/ml. These results
      suggest that EP( 2) and EP(4) receptors mediate the disruption of the blood
      aqueous barrier induced by EP receptor agonists and paracentesis.

PMID- 12789595
TI  - Seropositivity of human herpesvirus-8 in patients with uveitis.
AB  - PURPOSE: To explore the role of human herpesvirus-8 (HHV-8) in the pathogenesis
      of uveitis and other forms of ocular inflammation. METHODS: Serum antibody titers
      to HHV-8 were measured in 76 patients with uveitis from various causes and other
      types of ocular inflammation in either the acute phase, the convalescent phase,
      or both. RESULTS: Only one 21-year-old male patient in the convalescent phase of
      unilateral pars planitis showed a positive titer for HHV-8. His serum was
      negative for human immunodeficiency virus-1. CONCLUSIONS: Although the
      seropositive rate in the patient population was higher than that in the general
      population, the increased incidence was not statistically significant. The role
      of HHV-8 in the pathogenesis of intraocular inflammation appears to be limited.

PMID- 12789596
TI  - Presumed toxoplasmosic anterior optic neuropathy.
AB  - PURPOSE: To describe the clinical findings and course of toxoplasmic anterior
      optic neuropathy and to differentiate primary and secondary involvement. METHODS:
      Retrospective observational case series from a tertiary referral institution.
      Clinical and photographic charts of 13 patients with toxoplasmosis with direct
      optic nerve head involvement were reviewed and data were collected throughout the
      length of follow-up. RESULTS: Toxoplasmic anterior optic neuropathy was divided
      into two types. Type I was defined as secondary infectious involvement of the
      optic nerve head from an adjacent focus of chorioretinitis that resolved with
      chorioretinal scarring. Type II was defined as primary involvement of the optic
      nerve head that resolved without chorioretinal scarring. Visual acuity improved
      after treatment in both Type I and Type II patients; however, the visual
      prognosis was worse in Type I patients due to macular involvement. Eighty-three
      percent of Type II patients had a final visual acuity equal to or better than
      20/25 compared to 50% of Type I patients. Visual field defects were present in
      all patients, most frequently arcuate or altitudinal (62%). Delay in diagnosis
      was common (54%), especially in Type II patients (71%). Vitreous inflammation was
      absent on the initial examination in 31% of the patients. CONCLUSION: Toxoplasmic
      anterior optic neuropathy is an uncommon manifestation of ocular toxoplasmosis.
      Delays in diagnosis are common because of the frequent lack of typical
      chorioretinitis or vitreous inflammation. Adjacent macular involvement strongly
      influences visual outcome.

PMID- 12789597
TI  - A long-term follow-up of Eales' disease.
AB  - PURPOSE: To provide long-term follow-up information on Eales' patients. METHODS:
      Eales' patients, who had been examined at varying periods between the years 1970
      and 1991 with a minimum five-year follow-up, were included in the study. RESULTS:
      A total of 130 patients were followed up for a minimum of five and a maximum of
      26.5 years. The retinal lesions found during the first examination included
      vascular sheathing, disc and/or retinal neovascularization, vitreous hemorrhage,
      branch retinal vein occlusion, retinitis proliferans, and retinal detachment.
      Visual acuity improved in 37 (20%) of the 185 treated eyes, was maintained in 79
      (43%), and worsened in 69 (37%). The complications were tractional detachment,
      cataract, rubeosis iridis, neovascular glaucoma, and phthisis bulbi. CONCLUSION:
      The most important elements in dealing with Eales' disease are periodic follow
      up, a good and adequate laser treatment, pars plana vitrectomy combined with
      procedures for nonclearing vitreous hemorrhage, and retinal vasoproliferative
      changes to stabilize the retinal lesions and maintain functional levels of
      vision.

PMID- 12789598
TI  - Incidence of sympathetic ophthalmia after penetrating eye injury and choice of
      treatment.
AB  - INTRODUCTION: Sympathetic ophthalmia, a diffuse bilateral granulomatous
      panuveitis, is a serious potential complication after penetrating eye injury.
      Many surgeons recommend enucleation within two weeks of trauma to prevent this
      condition. We retrospectively reviewed the medical records of patients with
      penetrating ocular injuries who had either evisceration or enucleation to
      determine the incidence of sympathetic ophthalmia and to evaluate the surgical
      interventions and their complications. Age at surgery, time after penetrating
      trauma, surgery technique, follow-up period, ophthalmic examination of the fellow
      eye, and surgical complications were evaluated. RESULTS: In total, 217 patients
      were included in the study with a mean follow-up period of 10.3 +/- 6.6 years.
      The longest time between the trauma and time of surgery was 43 years.
      Postoperative uveitis was observed in only one patient (0.5%) who had primary
      repair after injury. Histopathological review did not reveal typical sympathetic
      ophthalmia. Complications after enucleation were significantly higher than after
      evisceration. CONCLUSION: There was no histopathologically supported sympathetic
      ophthalmia in our series. Sympathetic ophthalmia is very rare even when the
      injured eye is retained. With this in mind, the first choice of treatment may not
      be enucleation. Furthermore, evisceration may be the procedure of choice if
      primary repair cannot be performed or for patients who have panophthalmitis.

PMID- 12789600
TI  - Statins, super-statins and cholesterol absorption inhibitors.
AB  - An elevated level of low-density lipoprotein cholesterol (LDL-C) is an
      independent risk factor for premature coronary heart disease (CHD), with a value
      of > or = 160 mg/dl designated as high-risk by the National Cholesterol Education
      Program Adult Treatment Panels I, II and III. Current goals of therapy for all
      patients with elevated LDL-C include reducing levels to: (i) < 160 mg/dl in those
      with < or = 1 CHD risk factor; (ii) < 130 mg/dl in those with more than or equal
      to 2 CHD risk factors; and (iii) < 100 mg/dl in patients with established CHD or
      CHD risk equivalents, one of which is diabetes. The discovery of drugs that
      inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate
      limiting enzyme in cholesterol biosynthesis, constituted a major advance in the
      treatment of patients with elevated plasma concentrations of LDL-C. The efficacy
      of statins in LDL-lowering and CHD risk reduction has clearly been demonstrated
      in a number of primary and secondary intervention trials. Emerging options for
      the treatment of patients with elevated LDL-C include the super-statins
      rosuvastatin and pitavastatin, as well as the cholesterol absorption inhibitor
      ezetimibe. This article reviews large-scale clinical trials in which statins have
      been used to reduce LDL-C concentrations. Studies that have examined the efficacy
      and safety of rosuvastatin, pitavastatin and ezetimibe will also be discussed.

PMID- 12789599
TI  - Ocular toxoplasmosis presenting as neuroretinitis: report of two cases.
AB  - BACKGROUND: Neuroretinitis is a clinical entity usually seen in young healthy
      adults, that is characterized by rapid profound unilateral loss of vision and
      includes optic nerve head edema, splinter hemorrhages, macular exudate in a
      stellate pattern, and variable vitreous inflammation. There are numerous entities
      that can cause a picture of neuroretinitis ranging from vascular to infectious to
      autoimmune. PATIENT AND METHODS: We report two patients with neuroretinitis, who
      presented with unilateral blurred vision and had serologic evidence of Toxoplasma
      gondii infection. RESULTS: Both patients responded well to treatment with
      systemic antibiotics and corticosteroids. Visual acuity returned to 20/60 in one
      patient and 20/20 in the other. CONCLUSION: Although the etiology is usually
      idiopathic, infectious causes of neuroretinitis, including toxoplasmosis, should
      be kept in mind in order to maintain visual acuity by early diagnosis and
      appropriate therapy.

PMID- 12789601
TI  - Status of therapies in development for the treatment of age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is among the leading causes of visual
      impairment in the elderly. The FDA has approved only two treatments, laser
      photocoagulation and Visudyne photodynamic therapy (PDT), approved for the wet
      form of AMD, a progressive condition characterized by the presence of choroidal
      neovascularization (CNV). Current pharmaceutical activities aimed at the
      treatment of wet-type AMD are largely focused on the development of anti
      angiogenic drugs that would inhibit further CNV formation or even reduce existing
      CNV. However, other lines of attack for the treatment of wet AMD include anti
      inflammatory agents as well as new PDT agents. This review will summarize ongoing
      activities for these different approaches.

PMID- 12789602
TI  - Pentosan polysulfate as a prophylactic and therapeutic agent against prion
      disease.
AB  - Pentosan polysulfate (PPS) acts by imitating the physiological roles of the
      heparans. It binds to heparan binding sites on proteins and alters the
      physiological actions of these proteins. PPS acts as a prophylactic agent against
      infection with prions both in vivo and in vitro. Low concentrations (10 mg/ml)
      are needed extracellularly for this effect to be seen but, due to cellular
      uptake, it is believed that a much higher concentration is found intracellularly.
      The prophylactic effect of PPS is observed if the drug is administered to mice
      between 3 months before and approximately 30 days after the inoculation of the
      disease. After that point it is considered that the infection has entered the
      nervous system, and that the drug cannot penetrate the blood-brain barrier. The
      prophylaxis of humans with oral PPS and the current therapeutic activity of the
      drug when given by intracerebroventricular infusion to symptomatic, prion
      infected animals are discussed.

PMID- 12789603
TI  - SPM-927 (Schwarz Pharma).
AB  - Schwarz Pharma, under license from Harris FRC, is developing SPM-927, synthesized
      by researchers at the University of Houston, for the potential treatment of
      epilepsy and neuropathic pain.

PMID- 12789604
TI  - Pixantrone (Novuspharma).
AB  - Novuspharma is developing pixantrone, a second-generation, well-tolerated
      anthracenedione analog, for the potential treatment of lymphoma and multiple
      sclerosis.

PMID- 12789605
TI  - Potential treatments and treatment strategies in Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease is a rare neurodegenerative disease that follows a
      rapidly progressive course, leading to death, usually only a few months from
      onset. Over the last 30 years, many treatments have been tried for this
      condition, including a wide variety of antiviral agents and immunomodulating
      drugs. More recently, potential treatments have been devised that interfere with
      the pathological processes involved in the formation of the prion protein. Most
      of these experiments have been performed in in vitro and tissue culture models
      and have yet to be tried in human prion disease. As yet, no treatment has been of
      sustained benefit but, currently, a preliminary open-label trial of quinacrine is
      underway in the UK.

PMID- 12789606
TI  - Recent progress toward the clinical development of new anti-MRSA antibiotics.
AB  - The escalation in drug resistance is well documented for methicillin-resistant
      Staphylococcus aureus (MRSA) and the urgency to discover new antibiotic
      treatments is more apparent with the growing incidences of vancomycin
      intermediate and vancomycin-resistant S aureus. Much of the current research into
      finding new remedies focuses on chemical modification of existing antibiotics
      (ie, glycopeptides and cephalosporins) and developing synthetic molecules with
      novel mechanisms of action (ie, oxazolidinones and N-thiolated b-lactams). This
      review describes recent progress toward the clinical development of new drug
      therapies for MRSA.

PMID- 12789607
TI  - Multifunctional drugs for endothelial dysfunction in diabetes and glaucoma.
AB  - Endothelial dysfunction is a multifactorial term in that it encompasses a number
      of complex biochemical alterations in the ability of endothelial cells to perform
      their normal physiological function. These alterations are generally initiated by
      increased oxidative stress leading to pathological alterations in the cellular
      balance of mediators produced by endothelial cells. The key mediators include
      nitric oxide (NO), superoxide and endothelin. This review presents the current
      status of our knowledge of endothelial dysfunction in diabetes and in glaucoma
      and presents the case for evaluation of multifunctional drugs in these diseases.

PMID- 12789608
TI  - Chronogesic (DURECT).

PMID- 12789609
TI  - Merimepodib (Vertex).

PMID- 12789610
TI  - CEP-1347 (Cephalon).

PMID- 12789611
TI  - Vascular endothelial growth factor and anti-angiogenic peptides as therapeutic
      and investigational molecules.
AB  - The fundamental importance of angiogenesis in health and disease makes both
      inhibition and stimulation of blood vessel formation a major therapeutic goal.
      Vascular endothelial growth factor (VEGF) is the single most important angiogenic
      factor in disease-associated neovascularization and is both a major focus for the
      development of anti-angiogenic medicines for cancer and a candidate pro
      angiogenic cytokine for the treatment of ischemic heart disease. The development
      of VEGF-specific or vascular-specific peptides is an emerging approach to the
      design of therapeutic molecules targeted against pathophysiological angiogenesis.
      This article highlights recent progress toward the development of anti-angiogenic
      and vascular-specific peptides with a focus on peptidic VEGF receptor
      antagonists.

PMID- 12789613
TI  - The future prospects of oxazolidinones.
AB  - The high rates of antimicrobial resistance seen among many Gram-positive
      pathogens means that there is an ongoing need for new antibacterial drugs.
      Currently, several pharmaceutical companies are investigating compounds belonging
      to a new class of anti-Gram-positive agents, the oxazolidinones, one member of
      which, linezolid, is licensed for clinical use. Interest in oxazolidinones is
      being stimulated by the results of recent trials demonstrating the excellent
      clinical efficacy of linezolid in a range of infections. Linezolid is also a
      relatively safe drug, the main toxicity issue relating to development of
      thrombocytopenia in some patients receiving prolonged courses. With regard to new
      oxazolidinones, there is particular interest in analogs that, in early laboratory
      evaluation, show enhanced activity against the respiratory pathogens Haemophilus
      influenzae and Moraxella catarrhalis. The future potential of the oxazolidinones
      will depend on the antibacterial spectra, pharmacokinetic properties and toxicity
      profiles of new compounds, and the degree to which their clinical use may be
      affected by the emergence of oxazolidinone-resistant pathogens.

PMID- 12789612
TI  - Recently discovered sulfonamide-, acyl sulfonamide- and carboxylic acid-based
      endothelin antagonists.
AB  - Endothelins (ET-1, 2 and 3) are 21-residue peptides with two disulfide bridges
      and a highly conserved carboxy terminal. ET-1, the most significant isoform, is a
      potent vasoconstrictor and mitogen that exerts its biological effects through
      binding to its two G protein-coupled receptors: ET(A) and ET(B). ET(A) receptors
      are expressed on vascular smooth muscle cells and mediate vasoconstrictive and
      proliferative responses to ET-1. ET(B) receptors are mainly located on
      endothelial cells where they clear ET-1 from circulation and mediate vasodilation
      via the release of nitric oxide. ET-1 has been associated with a variety of
      serious diseases such as pulmonary hypertension, heart failure, prostate cancer
      and renal dysfunction.

PMID- 12789614
TI  - Aplidin PharmaMar.
AB  - Aplidin is a cell cycle inhibitor being developed by PharmaMar SA for the
      potential treatment of a variety of cancers, including non-Hodgkin's lymphoma
      (NHL), non-small-cell lung cancer (NSCLC), acute lymphoblastic leukemia (ALL),
      neuroendocrine, prostate, gastric and colorectal cancers [390131], [464778].

PMID- 12789615
TI  - NN-2211 Novo Nordisk.
AB  - Novo Nordisk A/S, under license from Scios Inc, is developing NN-2211, a stable
      analog of the naturally occurring peptide hormone glucagon-like peptide 1 (GLP
      1), which stimulates insulin release in response to increases in blood sugar
      levels, for the potential treatment of type 2 diabetes.

PMID- 12789617
TI  - Synthetic urokinase inhibitors as potential antitumor drugs.
AB  - Urokinase-mediated plasminogen activation is involved in many normal
      physiological processes, including tissue remodeling, embryogenesis, wound
      healing and clot lysis. In addition, elevated levels of urokinase, the urokinase
      receptor uPA-R and its endogenous inhibitor plasminogen activator inhibitor (PAI
      1), in combination with plasmin, play an important role in the pathogenesis of
      malignancy through its ability to mediate tumor cell growth, invasion and
      metastatic dissemination. The inhibition of urokinase with synthetic inhibitors
      is a new concept for a specific cancer therapy. This review examines synthetic
      urokinase inhibitors described during the last two years.

PMID- 12789616
TI  - Morphinan derivatives--A review of the recent patent literature.
AB  - Alkaloids extracted from the Papaverum somniferum are among the most powerfully
      acting and clinically used drugs for diseases of the central nervous system, in
      particular for pain. The basic ring system, common to these opiate alkaloids, is
      the morphinan skeleton, which in the last 50 years has been chemically
      manipulated to obtain compounds with improved potency and increased selectivity
      toward different populations of opioid receptors. Despite a huge amount of
      research, interest surrounding these compounds is still high. This review will
      discuss the patent applications published from January 2001 to June 2002,
      focusing on new chemical entities that could become drugs over the next few
      years, new chemical processes for the production of the morphinans currently used
      in therapy, novel formulations and combined compositions.

PMID- 12789618
TI  - Drug therapy for amyotrophic lateral sclerosis: Where are we now?
AB  - In the 60 years since Lou Gehrig died from amyotrophic lateral sclerosis (ALS)
      there have been numerous advances in our understanding of this disease. However,
      scant progress has been made regarding disease-altering treatments. Today most
      physicians still recommend vitamin E, which is the treatment Gehrig himself
      received. In this paper we will review what is currently known about the
      pathophysiology of ALS as well as the history of clinical trials in ALS. We
      indicate current and future directions in research and clinical trials, and also
      argue that a logical next step for clinical trials in ALS should be combination
      drug treatment.

PMID- 12789619
TI  - Pralnacasan (vertex pharmaceuticals).
AB  - Vertex is collaborating with Aventis Pharma AG (formerly Hoechst Marion Roussel
      Inc) in the development of pralnacasan, an interleukin (IL)-1b converting enzyme
      (ICE) inhibitor, for the potential treatment of inflammatory diseases [170247],
      [188293], [453094].

PMID- 12789620
TI  - Ruboxistaurin (Eli Lilly).
AB  - Eli Lilly & Co is developing the protein kinase C (PKC)-b inhibitor
      ruboxistaurin, the lead compound from a series of 14-membered macrocycles, for
      the potential treatment of diabetic retinopathy, diabetic peripheral neuropathy
      and macular edema.

PMID- 12789621
TI  - Stereoselectivity of drug-receptor interactions.
AB  - Stereochemical aspects of drug action have intrigued researchers ever since (and
      even before) the introduction of the receptor concept. Easson and Stedman first
      formalized this by suggesting the three-point tethering of an asymmetric ligand
      to its macromolecular target. Today, enantioselectivity is increasingly
      understood in molecular and atomic detail. Through site-directed mutagenesis, the
      amino acids responsible for the stereoselective recognition of ligand molecules
      have been identified in a number of cases, in particular for the b(2)-adrenergic
      receptor, a prototypic G protein-coupled receptor. Novel ligands with one or more
      chiral centers and complicated stereochemistry continue to be developed as
      potential medicines, despite reservations put forward by regulatory agencies. In
      this review, recent achievements in this respect will be discussed for a number
      of receptor (sub)families, and some general thoughts will be presented on the
      stereoselectivity of drug action.

PMID- 12789622
TI  - Inhibitors of the NOS enzymes: a patent review.
AB  - This review covers the recent literature on inhibitors of nitric oxide synthase
      (NOS) between 2001 and June 2002. Some of the potential therapeutic uses of
      selective NOS inhibitors are highlighted in the introduction, while the main part
      of the review covers the patent literature of small molecule NOS inhibitors being
      investigated primarily by the pharmaceutical industry.

PMID- 12789623
TI  - LY-354740 (Eli Lilly).
AB  - Lilly is developing LY-354740, the lead compound in a series of derivatives of
      the metabotropic glutamate receptor group II agonist L-CCG-1, for the potential
      treatment of anxiety [212536], [276941], [276942].

PMID- 12789624
TI  - BMS-214662 (Bristol-Myers Squibb).
AB  - Bristol-Myers Squibb is developing BMS-214662, a farnesyl transferase inhibitor,
      for the potential treatment of cancer. By October 2000, preclinical
      investigations were ongoing in Japan. By February 2001, the drug was in phase II
      trials in the US for pancreatic, head and neck, lung and colorectal cancers.

PMID- 12789625
TI  - [From PRK to LASEK, and from LASEK to PRK].

PMID- 12789626
TI  - [Vitreous body amino acids control group].

PMID- 12789627
TI  - [Iris-claw phakic intraocular lens for high myopia correction. Visual and
      refractive results].
AB  - PURPOSE: To determine predictability, efficacy, complications and patient's
      satisfaction to phakic intraocular lens (Artisan) in highly myopic patients.
      METHOD: Retrospective study of 65 eyes (36 patients), with preoperative spherical
      equivalent (SE) between -9,75 and -25,0 diopters (D) operated on by a single
      surgeon (JAD) between January 1999 and August 2001. Uncorrected visual acuity
      (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, postoperative
      complications, and patient's subjective response were evaluated. RESULTS: UCVA
      evaluated 3 months postoperatively was 0.47 and BSCVA was 0.62. An average gain
      of 2.3 lines was observed with respect to the preoperative BSCVA. Refraction
      between +/-0.50 D from emmetropia ocurred in 49.23% of the eyes, and between +/-
      1.0 D in 78.46% of the eyes. The difference between intended SE (preoperative SE
      minus IOL diopter) and achieved postoperative SE, showed a 0.55 D mean
      undercorrection. An intraocular pressure (IOP) over 30 mmHg was seen in 10% of
      the eyes in the immediate postoperative period. Night halos/glare perception was
      <<mild>> in 20% of the eyes, and in 90.77% of the cases the patient showed
      satisfaction with the results of the procedure. CONCLUSION: Artisan iris-claw
      phakic lens implantation in highly myopic eyes is a safe procedure that increases
      BSCVA. It was observed a tendency towards undercorrection in the postoperative
      refractive outcome.

PMID- 12789628
TI  - [Topical versus contact anaesthesia in conventional trabeculectomy. Prospective
      randomised study].
AB  - PURPOSE: To compare the pain rates, comfort levels and safety between
      conventional topical anaesthesia and the application of a long lasting lidocaine
      soaked film or contact anaesthesia. METHODS: Fifty patients undergoing
      conventional trabeculectomy with or without Mitomycin-C were included. One half
      received topical anaesthesia and the other half contact anaesthesia in a random
      fashion. Pain and discomfort rates before, during and after surgery were
      evaluated on a scale from 0 to 5, also, surgeon subjective stress and
      complications observed were included in the clinical protocol. RESULTS:
      Significant differences were found between both groups regarding pain rates,
      during and after surgery, and surgeon stress level. Sedation and change of
      anesthesic method were required more frequently by the patients included in the
      topical anaesthesia group. CONCLUSIONS: Topical anaesthesia provides sufficient
      level of anaesthesia for performing a trabeculectomy. Nevertheless pain rate
      differences between contact and conventional topical anaesthesia were patent
      during and after surgery. Contact anaesthesia appears to be a valid and practical
      alternative in a wide range of patients undergoing glaucoma surgery.

PMID- 12789629
TI  - [Measure of the fatty layer thickness of precorneal tear film by interference
      colours in different types of dry eye].
AB  - PURPOSE: Measure the thickness of lacrimal fatty layer in several pathologies
      with ocular dryness, by the study of interferencial colours. METHODS: A
      prospective study of 100 patients (50 males and 50 females), divided in ten
      groups was performed. The first nine groups had dry eye pathology, the other one
      was the control group of healthy patients. We measured with the slit lamp the
      fatty layer thickness by the study of interferencial colours. RESULTS: We found a
      greater thickness of the fatty layer in patients with pathologies like seborrheic
      blepharitis, keratoconjunctivitis sicca, chronic blepharitis and contact lens
      wear, compared with the control group. Patients with climatic and ambiental dry
      eye had a thin fatty layer compared with the control group. We didn't find
      statisticaly significative differences between control group and the patients
      with chronic conjunctivitis or atopic conjunctivitis. CONCLUSIONS: The thickness
      of the fatty layer changes in different dry eye pathologies. Interferencial
      colours study is a semiquantitative and non invasive method to measure the
      thickness of fatty layer of precorneal tear film. It s easy to perform and
      interprete, so we must include this as a part of the dry eye diagnostic study.

PMID- 12789630
TI  - [Interferon alfa-2b treatment in selected cases of recurrent conjunctival
      intraepithelial neoplasia].
AB  - PURPOSE: To study the efficacy of topical and combined topical and
      subconjunctival interferon alfa 2b (IFN alfa 2b) in the treatment of recurrent
      conjunctival intraepithelial neoplasia (CIN) in those patients who present
      resistance or intolerance to topical mitomycin C (MMC) treatment or when it is
      not indicated. METHODS: Four patients (age range from 52 to 70) with histological
      confirmation of recurrent CIN were studied prospectively. Two patients were
      resistant to topical MMC, another one did not tolerate it, and in the last case,
      this treatment was not indicated due to a stem cell insufficiency associated to a
      trophic corneal ulcer. Three patients were given just topical interferon (1
      million IU/ ml four times a day for three months), while the last one received
      topical therapy and subconjunctival IFN alfa 2b injections (3 millions IU/ 0.5
      ml). RESULTS: Complete regression of the tumour was evident in all cases. sixteen
      to 24 months after treatment no patient had clinical evidence of recurrence. No
      side effects were observed in any patient, not even with subconjunctival
      administration. CONCLUSIONS: IFN alfa 2b is effective as an alternative treatment
      to topical MMC in selected cases of recurrent CIN.

PMID- 12789631
TI  - [Double scleral covering evisceration].
AB  - PURPOSE: To describe a surgical technique for evisceration that allows the use of
      large size implants, reducing risk of exposure. MATERIAL AND METHODS: We analize
      the results of 22 eviscerations with Medpor implants with double scleral
      covering. RESULTS: We managed to use implants of 20 and 22 mm, sometimes in very
      small anophthalmic cavities, without complications. CONCLUSIONS: Double scleral
      covering evisceration is a surgical technique that allows the use of large size
      implants, reducing the risk of exposure.

PMID- 12789633
TI  - [Endogenous serratia marcescens endophthalmitis diagnosis with PCR].
AB  - PURPOSE/METHOD: We report the case of a 75-year-old man with endogenous
      endophthalmitis in the left eye. Culture results were negative. PCR for several
      Gram-negative bacterias genome was performed. RESULTS/CONCLUSIONS: Polymerase
      chain reaction showed amplification of Serratia marcescens genome. Our case
      indicates that PCR can be a valuable tool in the diagnosis of culture negative
      endophthalmitis.

PMID- 12789632
TI  - [Verteporfin and photosensitivity in diabetic].
AB  - PURPOSE/METHOD: A 33-year-old woman with a myopic neovascular lesion was treated
      with photodynamic therapy (PDT) with verteporfin. She had a borde-line diabetes
      mellitus that finally needed treatment with a sulfonylurea. She underwent a
      second treatment with PDT that was uneventful, but 10 hours later she experienced
      severe skin photosensitivity reaction. RESULTS/CONCLUSIONS: As the use of
      verteporfin becomes more widespread around the world, physicians must be alert to
      the possibility of adverse side effects associated with its use and its
      interaction with other drugs.

PMID- 12789634
TI  - [Ocular accommodation. (1931)].

PMID- 12789635
TI  - [Prospect of Nineteen Century].

PMID- 12789636
TI  - [Ineffective anticoagulation prior to elective electric cardioversion for atrial
      fibrillation. Results of transesophageal echocardiography].
AB  - BACKGROUND AND OBJECTIVE: Anticoagulation (AC) should be given for 3 to 4 weeks
      before elective electrical cardioversion to reduce thromboembolic events. During
      this period ineffective AC is a common problem. The aim of our study was to
      investigate the influence of the duration of ineffective AC on the incidence of
      left atrial thrombi (LAT) or spontaneous echocontrast (SEC) induced by hemostasis
      detected by transesophageal echocardiography (TEE). PATIENTS AND METHODS: 56
      consecutive patients (39 men) at the age of 64 +/- 9 years with non-rheumatic
      atrial fibrillation who were scheduled for electrical cardioversion after 3 to 4
      weeks of AC and a documented ineffective AC underwent TEE. Cardioversion was
      performed after exclusion of a LAT by TEE or in patients with LAT after 4 more
      weeks of AC and repeated TEE. All patients received AC and were observed for at
      least 4 weeks after cardioversion. Echocardiographic, demographic and clinical
      parameters and available values of AC were recorded. RESULTS: In 5/56 (9 %)
      patients a LAT, in 10 (18 %) patients SEC was detected. No patient had both. In
      patients with LAT the duration of ineffective AC was 15 +/- 10 days (range 5 -
      28) and did not differ significantly from patients without LAT (17 +/- 8 days;
      range 0 - 28) or to the group with SEC (23 +/- 6 days; range 12 - 28). There was
      no significant difference of demographic, echocardiographic and clinical
      parameters between these groups. There was no embolic event during follow-up.
      CONCLUSIONS: Neither the duration of ineffective AC nor clinical, epidemiologic
      or echocardiographic parameters could differentiate patients with or without LAT
      in our observed groups with small numbers of patients. In case of an ineffective
      AC patients who are to undergo electrical cardioversion should have TEE. In our
      study patients with SEC were not at a higher thromboembolic risk.

PMID- 12789637
TI  - [Excessive hyperferritinemia as an indication of a reactive hemophagocytosis
      syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 17-year-old girl with a history of a
      polyarthritis of unknown etiology was admitted because of acute fever and general
      weakness. There were palpable cervical lymph nodes and her body temperature was
      39.5 degrees C. INVESTIGATIONS: GOT was raised to 282 U/1, GPT to 266 U/l lactate
      dehydrogenase to 1275 U/I and bilirubin to 0.6 mg/dl. The Quick value was 67%,
      albumin 28 mg/dl. White cell count was decreased to 1700/microl, with 43%
      granulocytes, 39% lymphocytes, 17% monocytes. Platelet count was 64,000/microl.
      Ultrasound revealed splenomegaly. Ferritin was markedly raised to 11,860 ng/ml
      (normal up to 150 ng/ml). An epstein-barr-virus infection was found. THERAPY AND
      CLINICAL COURSE: Suspecting a reactive hemophagocytosis syndrome, she was treated
      with prednisolone (2 mg/kg). The diagnosis was confirmed by a bone marrow
      aspirate. The patient's condition and laboratory values improved rapidly.
      CONCLUSION: Markedly increased ferritin levels in a clinically septic patient
      with an underlying rheumatic disease indicates a hemophagocytotic syndrome. High
      dosage steroid should be started before there is biopsy confirmation of the
      disease.

PMID- 12789638
TI  - [Malaria--case report].

PMID- 12789639
TI  - [Malaria--diagnosis].

PMID- 12789640
TI  - [Malaria--treatment].

PMID- 12789643
TI  - [Porcine endogenous retroviruses (PERVs) and xenotransplantation. A risk for the
      recipient and for society?].

PMID- 12789644
TI  - [Truth imparting in the hospital].

PMID- 12789645
TI  - [Liability of the physician in the refusal of a clinic admission by the patient.
      Decision of the Provincial High Court of Zweibrucken from August 20, 2002--5 U
      25/01].

PMID- 12789646
TI  - Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin
      extracellular-matrix linker protein UNC-112, causes Kindler syndrome.
AB  - Kindler syndrome is an autosomal recessive disorder characterized by neonatal
      blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the
      skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in
      additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations
      were identified in the FLJ20116 gene (renamed "KIND1" [encoding kindlin-1]).
      Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a
      membrane-associated structural/signaling protein that has been implicated in
      linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler
      syndrome is, to our knowledge, the first skin fragility disorder caused by a
      defect in actin-ECM linkage, rather than keratin-ECM linkage.

PMID- 12789649
TI  - Islet transplantation: where do we stand now?
AB  - After many years of limited success in islet transplantation, researchers
      developing this procedure have made great strides, and several centers have now
      reported that islet transplantation can result in long-term insulin independence
      for patients with type 1 diabetes mellitus. The improved quality of life achieved
      in some islet allograft recipients suggests that this important line of
      investigation should proceed. Yet, several factors limit the technique and these
      hurdles must be overcome before it can be considered a practical treatment for
      the millions of individuals with diabetes, be it type 1 or type 2. Most obvious
      is the gross disparity between the number of islets available for clinical
      transplantation and the number of patients with diabetes who might benefit. Other
      important limitations, too often lost in the discussion, include complications
      associated with the technique itself, the toxicity of currently available
      immunosuppressive drugs, and the imperfect glycemia control achieved in most
      patients. In fact, our ongoing analysis as to whether transplantation-based
      therapy improves survival for patients with type 1 diabetes suggests that, for
      many at least, the opposite may be true. Two variables, as yet undefined, also
      need to be considered: (1) can the procedure, when done well, prevent or reverse
      diabetes-associated complications and (2) what are the long-term consequences of
      intrahepatic islets?

PMID- 12789647
TI  - Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype.
AB  - Mutations in TBX5, a T-box-containing transcription factor, cause cardiac and
      limb malformations in individuals with Holt-Oram syndrome (HOS). Mutations that
      result in haploinsufficiency of TBX5 are purported to cause cardiac and limb
      defects of similar severity, whereas missense mutations, depending on their
      location in the T box, are thought to cause either more severe heart or more
      severe limb abnormalities. These inferences are, however, based on the analysis
      of a relatively small number of independent cases of HOS. To better understand
      the relationship between mutations in TBX5 and the variable expressivity of HOS,
      we screened the coding and noncoding regions of TBX5 and SALL4 for mutations in
      55 probands with HOS. Seventeen mutations, including six missense mutations in
      TBX5 and two mutations in SALL4, were found in 19 kindreds with HOS. Fewer than
      50% of individuals with nonsense or frameshift mutations in TBX5 had heart and
      limb defects of similar severity, and only 2 of 20 individuals had heart or limb
      malformations of the severity predicted by the location of their mutations in the
      T box. These results suggest that neither the type of mutation in TBX5 nor the
      location of a mutation in the T box is predictive of the expressivity of
      malformations in individuals with HOS.

PMID- 12789650
TI  - Negative T cell costimulation and islet tolerance.
AB  - Activation of self-reactive T cells that specifically destroy the pancreatic beta
      cells is one of the hallmarks in the development of type 1 diabetes. Thus, for
      prevention and treatment of this autoimmune disease, approaches to induce and
      maintain T cell tolerance toward the beta-cells, especially in islet
      transplantation, have been actively pursued. Noticeably, many of the recent
      protocols for inducing transplant tolerance involve blockade of positive T cell
      costimulation extrinsically. Though highly effective in prolonging graft
      survival, these strategies alone might not be universally sufficient to achieve
      true tolerance. As the mystery of the suppressive and regulatory T cells unfolds,
      it is becoming appreciated that exploiting the intrinsic molecular and cellular
      mechanisms that turn off an immune response would perhaps facilitate the current
      protocols in establishing T cell tolerance. In this perspective, here we
      summarize the recent findings on the negative costimulation pathways, in
      particular, the newly identified PD-1 : PD-L interactions. On the basis of these
      observations, we propose a new principle of curtailing pathogenic T cell response
      in which blockade of positive T cell costimulation is reinforced by concurrent
      engagement of the negative costimulation machinery. Such a strategy may hold
      greater hope for therapeutic intervention of transplant rejection and autoimmune
      diseases.

PMID- 12789651
TI  - Chemokines in islet allograft rejection.
AB  - Chemokines have emerged as important regulators in the development,
      differentiation, and anatomic distribution of leukocytes. Studies of renal and
      cardiac allograft biopsies have revealed that the expression of many chemokine
      receptors and their ligands was associated with acute allograft rejection.
      However, the importance of these chemokine receptor systems varies in the host
      response to a particular allograft. In this regard, CXCR3 appears to play a more
      important role in cardiac allograft rejection than CCR2 and CCR5. We have found
      that CCR2, CCR5, and CXCR3 and their ligands, as well as Th1 cytokines are
      induced to high levels in rejecting islet allografts. Interestingly, targeting
      CCR5 resulted in a significant prolongation of islet allograft survival. This
      prolongation was associated with a Th2 response. Our data indicate that in the
      process of acute rejection, the temporal expression and the ultimate function of
      a given chemokine vary among different organs or tissues. Hence, each organ or
      tissue may require a unique set of chemokines to generate acute rejection.
      Targeting the appropriate chemokine receptors may provide a clinically useful
      strategy to prevent islet allograft rejection.

PMID- 12789652
TI  - Genes expressed in the developing endocrine pancreas and their importance for
      stem cell and diabetes research.
AB  - The genes that regulate endocrine pancreas development, maintain adult endocrine
      cells, and stimulate progenitor/stem cells during regeneration remain largely
      unstudied. There is ample evidence that many of the genes involved in endocrine
      pancreas development also function in the homeostasis of the adult islet. In
      light of the potential benefits to diabetic research, it is surprising that there
      is little information about the genes expressed throughout the ontogeny of the
      endocrine pancreas. In the past few years, efforts have been made to establish
      the Endocrine Pancreas Consortium database (EPConDB), in which many of the genes
      expressed in the developing endocrine pancreas are in a database with a
      corresponding publicly available clone bank. In addition, advances in microarray
      technology now allow for a quantitative expression analysis of thousands of genes
      simultaneously, which makes it possible to generate a quantitative catalog of the
      genes expressed at each step of endocrine differentiation, from embryonic
      endoderm to mature beta cells. In this review, I will discuss how genes
      discovered by virtue of their role in endocrine pancreas development may function
      in the maintenance of pancreatic stem cells and the regeneration of islets. I
      will further summarize the recent advances in genomics-based studies of the
      developing endocrine pancreas and will discuss how they might impact on the
      discovery of diagnostics and research into stem cell-based approaches for the
      treatment of diabetes.

PMID- 12789653
TI  - Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample.
AB  - OBJECTIVE: There is some evidence to suggest that individuals with depression are
      at an almost twofold increased risk of developing type 2 diabetes mellitus, but
      results are far from conclusive. Therefore, to determine if depressive symptoms
      increased the risk of type 2 diabetes, we conducted longitudinal analyses using
      data from the NHANES I Epidemiologic Follow-up Survey (NHEFS). RESEARCH DESIGN
      AND METHODS: Participants included individuals who were white or African
      American, did not report previous diagnosis of diabetes, and who completed the
      Centers for Epidemiologic Studies Depression (CES-D) questionnaire in the 1982
      1984 study (n = 8870). Participants were followed up for incident-diagnosed
      diabetes through 1992 (mean follow-up 9.0 years). RESULTS: There were 1444
      (15.9%) participants with high depressive symptoms in the 1982-1984 study (CES-D
      score > or = 16). During follow-up, there were 465 incident cases of diabetes.
      Incidence of diabetes was 6.9/1000 person years among those with high depressive
      symptoms, 6.0/1000 person years among those with moderate symptoms, and 5.0/1000
      person years among those with no symptoms. After adjusting for age, sex, and
      race, the relative hazard (RH) of diabetes among those with high depressive
      symptoms was 1.27 (95% CI: 0.93 to 1.73) compared to those without symptoms.
      Further adjustment for education and known diabetes risk factors (body mass index
      and physical activity) further attenuated the relationship (RH 1.11, 95% CI: 0.79
      to 1.56). CONCLUSIONS: There was no increased incidence of diabetes for those
      with high or moderate depressive symptoms compared to those with no depressive
      symptoms. These results do not support the etiologic relationship of depression
      predisposing individuals to diabetes.

PMID- 12789654
TI  - Increase in adenosine A1 receptor gene expression in the liver of streptozotocin
      induced diabetic rats.
AB  - BACKGROUND: Adenosine A1 receptor (A1-AR) activation can lower plasma glucose in
      diabetic rats lacking insulin. We investigated the change in A1-AR gene
      expression in diabetic rats. METHODS: The incorporation of [U-(14)C]-glucose into
      glycogen was carried out to evaluate the effect of N(6)-cyclopentyladenosine
      (CPA) on glucose utilization in vitro. The plasma glucose concentration was
      assessed by the glucose oxidase method. The mRNA and protein levels of A1-AR in
      isolated liver were detected by Western blotting analysis and Northern blotting
      analysis, respectively. RESULTS: The effect of CPA, an agonist of A1-AR, on
      glycogen incorporation in hepatocytes isolated from streptozotocin-induced
      diabetic rats (STZ-diabetic rats) was more marked than that from the normal rats.
      However, similar glycogen synthesis was not modified by 12-O-tetradecanoylphorbol
      13-acetate (TPA), an activator of protein kinase C, in the isolated hepatocytes
      from both the normal and the STZ-diabetic rats. A change in response at the
      receptor level can thus be considered. The mean level of liver mRNA transcripts
      encoding A1-AR was increased in STZ-diabetic rats to about 250% of that in normal
      rats. Exogenous insulin at a dose sufficient to normalize the plasma glucose of
      STZ-diabetic rats reversed the mRNA level of A1-AR in the liver after a four-day
      treatment. Similar results were also observed in STZ-diabetic rats that received
      treatment with phlorizin for four days. Moreover, the protein level of A1-AR was
      higher in the liver of STZ-diabetic rats than that in the normal rats. Similar
      treatment with exogenous insulin or phlorizin reversed the elevated protein level
      of A1-AR in the liver of STZ-diabetic rats to near the normal level. Therefore,
      correction of hyperglycemia in STZ-diabetic rats can reverse the higher gene
      expression of A1-AR in liver. CONCLUSIONS: The obtained results suggest that an
      increase in plasma glucose is responsible for the higher gene expression of A1-AR
      in the liver of STZ-diabetic rats.

PMID- 12789655
TI  - Prevalence of psychiatric disorders in an onset cohort of adults with type 1
      diabetes.
AB  - BACKGROUND: Previous studies indicate a high prevalence of psychiatric disorders
      in adults with type 1 diabetes mellitus. The aim of our study was to determine if
      newly diagnosed adults with type 1 diabetes already have an elevated rate of
      psychiatric disorders at the beginning of their physical illness. METHODS: The
      authors consecutively recruited 313 newly diagnosed, adult inpatients with type 1
      diabetes (age 17-40 years) from 12 hospitals. A national, representative
      population sample of 2046 persons of a similar age range served as the reference
      group. Psychiatric disorders were measured in both groups using structured
      interviews that provided diagnoses according to DSM-IV. RESULTS: There was a
      point prevalence of 12.5% for psychiatric disorders in the sample. The most
      frequent conditions were anxiety and affective disorders. Subjects with type 1
      diabetes demonstrated a rate of major depressive episodes twice that of the
      reference group (5.8% vs 2.7%, p < 0.003; corrected for confounders). Apart from
      this finding, there was no significantly increased prevalence of psychiatric
      disorders in the diabetes sample as compared to the general German population.
      CONCLUSION: The rate of major depressive episodes in the new onset cohort of type
      1 diabetes patients was double that of the population as a whole. However, the
      hypothesis, that newly diagnosed type 1 diabetes patients have more psychiatric
      disorders than the general population, was not confirmed.

PMID- 12789658
TI  - Management of cerebral oedema in diabetes.

PMID- 12789656
TI  - Minalrestat and leukocyte migration in diabetes mellitus.
AB  - BACKGROUND: We recently demonstrated that aldose reductase inhibition was
      effective in restoring the reduced migratory capacity of leukocytes in diabetic
      rats. To investigate the mechanism(s) involved in the restoring effect, we used
      minalrestat, an aldose reductase inhibitor. METHODS: In sodium pentobarbital
      anesthetized (40 mg/kg, intraperitoneally) alloxan-diabetic or galactosemic male
      Wistar rats, the internal spermatic fascia was exteriorized, and the number of
      leukocytes rolling along the venular endothelium and the number of leukocytes
      sticking to the vascular wall after topical application of zymosan-activated
      plasma or leukotriene B(4) (1 ng/ml), as well as after the application of a local
      irritant stimulus (carrageenan, 100 microg), were determined using intravital
      microscopy. Data from animals that were treated with and those that were not
      treated with minalrestat (10 mg/kg/d by gavage) were compared. RESULTS: The
      reduced number of leukocytes rolling along the venular endothelium (by about 70%)
      and the number of adhered and migrated leukocytes in postcapillary venules (by
      60%) were significantly restored to control values after minalrestat treatment.
      Total or differential leukocyte counts, venular blood flow velocity or wall shear
      rate were not altered by minalrestat treatment. The expression of ICAM-1 and P
      selectin, cell adhesion molecules involved in the interaction of leukocyte
      endothelium, reduced in diabetic rats was restored by minalrestat treatment.
      CONCLUSION: We conclude that an enhanced flux through the polyol pathway might be
      involved in the reduced expression of ICAM-1 and P-selectin contributing to the
      impaired leukocyte-endothelial interactions in diabetes mellitus and that aldose
      reductase inhibition restores the defect, restoring the reduced expression.

PMID- 12789657
TI  - Recall of severe hypoglycaemia and self-estimated state of awareness in type 1
      diabetes.
AB  - BACKGROUND: The ability of people with insulin-treated diabetes to remember
      severe hypoglycaemia and the consistency of their self-estimated awareness of
      hypoglycaemia are not well documented but are important in clinical practice. The
      aim of this study is to assess recall of severe hypoglycaemia in patients with
      type 1 diabetes and to evaluate the feasibility of a simple method for clinical
      classification of the awareness of hypoglycaemia. METHODS: A one-year prospective
      study was performed on a cohort of patients with type 1 diabetes (n = 230). The
      rate of severe hypoglycaemia reported retrospectively at the end of the study was
      compared to the prospectively recorded rate during the study period. Self
      estimated awareness was explored in questionnaires at baseline and at the end,
      and assessments were evaluated by the occurrence of severe hypoglycaemic
      episodes. RESULTS: Almost 90% of the participants correctly recalled whether they
      had had severe hypoglycaemia. However, those with high prospectively recorded
      numbers had incomplete recall, resulting in a 15% underestimation of the overall
      rate. On the basis of the answer to the question "Do you recognise symptoms when
      you have a hypo?", the population was classified into three groups: 40% with
      normal awareness, 47% with impaired awareness and 13% with unawareness. The
      groups with impaired awareness and unawareness had 5.1 and 9.6 times higher rates
      of severe hypoglycaemia, respectively, compared to the group with normal
      awareness (p < 0.001). CONCLUSION: People with type 1 diabetes generally remember
      severe hypoglycaemic episodes during a one-year period. A simple method is
      proposed for classifying the state of awareness of hypoglycaemia in clinical
      practice.

PMID- 12789659
TI  - Current literature in diabetes.

PMID- 12789660
TI  - IQGAPs: integrators of the cytoskeleton, cell adhesion machinery, and signaling
      networks.

PMID- 12789661
TI  - CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by
      different mechanisms.
AB  - CLIP-170 is a "cytoplasmic linker protein" implicated in endosome-microtubule
      interactions and in control of microtubule dynamics. CLIP-170 localizes
      dynamically to growing microtubule plus ends, colocalizing with the dynein
      activator dynactin and the APC-binding protein EB1. This shared "plus-end
      tracking" behavior suggests that CLIP-170 might interact with dynactin and/or
      EB1. We have used site-specific mutagenesis of CLIP-170 and a
      transfection/colocalization assay to address this question in mammalian tissue
      culture cells. Our results indicate that CLIP-170 interacts, directly or
      indirectly, with both dynactin and EB1. We find that the CLIP-170/dynactin
      interaction is mediated by the second metal binding motif of the CLIP-170 tail.
      In contrast, the CLIP-170/EB1 interaction requires neither metal binding motif.
      In addition, our experiments suggest that the CLIP-170/dynactin interaction
      occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the
      cytosol (i.e., it does not require microtubule binding). These results have
      implications for the targeting of both dynactin and EB1 to microtubule plus ends.
      Our data suggest that the CLIP-170/dynactin interaction can target dynactin
      complex to microtubule plus ends, although dynactin likely also targets MT plus
      ends directly via the microtubule binding motif of the p150(Glued) subunit. We
      find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1,
      indicating that EB1 can target microtubule plus ends independently of dynactin.

PMID- 12789662
TI  - Control of flatfish sperm motility by CO2 and carbonic anhydrase.
AB  - Sperm motility in flatfishes shows unique characteristics. The flagellar movement
      either in vivo or in permeabilized models is arrested by the presence of 25-100
      mM HCO3-, or by gentle perfusion with CO2 gas. To understand the molecular basis
      of this property, sperm Triton-soluble proteins and flagellar proteins from
      several species were analyzed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. An abundant 29-kDa protein was observed only in flatfish
      species. Partial amino acid sequences identified this protein as a carbonic
      anhydrase, an enzyme involved in the interconversion of CO2 and HCO3-. 6
      ethoxyzolamide, a specific inhibitor of carbonic anhydrase inhibits sperm
      motility, especially at low pH. In the case of HCO3(-)-arrested sperm, the
      motility is restored by addition of 6-ethoxyzolamide. Taken together, these
      results suggest that a novel pH/HCO3(-)-dependent regulatory mechanism mediated
      by carbonic anhydrase is involved in the motility control in flatfish sperm.

PMID- 12789663
TI  - Reconstruction of the projection periodicity and surface architecture of the
      flagellar central pair complex.
AB  - The substructure of central pair microtubule-associated components has been
      analyzed by comparing thin section and freeze-etch images of Chlamydomonas
      flagellar axonemes. The longitudinal periodicity of central pair projections that
      were previously described from cross-sectional image averages was determined from
      thin sections of axonemes isolated from either wild type or central pair assembly
      defective strains. All projections directed toward one quadrant of the central
      pair repeat at 32 nm, while those in the other three quadrants all show 16-nm
      spacing. The surface architecture of these projections as seen in rapid-freeze
      deep-etch images of central pair complexes includes elements that form
      circumferentially oriented fibers around most of the central pair. This
      appearance changes dramatically along the lateral edge of the C1 microtubule
      where material is arranged in rows of separate particles that may play a unique
      role in spoke-mediated regulation of flagellar dynein activity.

PMID- 12789664
TI  - Genomic organization, alternative splicing, and expression of human and mouse N
      RAP, a nebulin-related LIM protein of striated muscle.
AB  - Linkage analysis identifies 10q24-26 as a disease locus for dilated
      cardiomyopathy (DCM), a region including the N-RAP gene. N-RAP is a nebulin-like
      LIM protein that may mediate force transmission and myofibril assembly in
      cardiomyocytes. We describe the sequence, genomic structure, and expression of
      human N-RAP, as well as an initial screen to determine whether N-RAP mutations
      cause cardiomyopathy. Human expressed sequence tag databases were searched with
      the published 3,528-bp mouse N-RAP open reading frame (ORF). Putative cDNA
      sequences were interrogated by direct sequencing from cardiac and skeletal muscle
      RNA. We identified two human N-RAP isoforms with ORFs of 5,085 bp (isoform C) and
      5,190 bp (isoform S), encoding products of 193-197 kDa. Genomic database searches
      localize N-RAP to human chromosome 10q25.3 and match isoforms C and S to 41 and
      42 exons. Only isoform C is detected in human cardiac RNA; in skeletal muscle,
      approximately 10% is isoform C and approximately 90% is isoform S. We
      investigated apparent differences between human N-RAP cDNA and mouse sequences.
      Two mouse N-RAP isoforms with ORFs of 5,079 and 5,184 bp were identified with
      approximately 85% similarity to human isoforms; published mouse sequences include
      cloning artifacts truncating the ORF. Murine and human isoforms have similar gene
      structure, tissue specificity, and size. N-RAP is especially conserved within its
      nebulin-like and LIM domains. We expressed both N-RAP isoforms and the previously
      described truncated N-RAP in embryonic chick cardiomyocytes. All constructs
      targeted to myofibril precursors and the cell periphery, and inhibited myofibril
      assembly. Several human N-RAP polymorphisms were detected, but none were unique
      to cardiomyopathy patients. N-RAP is highly conserved and exclusively expressed
      in cardiac and skeletal muscle. Genetic abnormalities remain excellent candidate
      causes for cardiac and skeletal myopathies.

PMID- 12789665
TI  - Requirement for the betaI and betaIV tubulin isotypes in mammalian cilia.
AB  - Nielsen et al., [2001: Curr Biol 11:529-533], based on studies in Drosophila,
      have proposed that beta tubulin in axonemal microtubules must contain a specific
      acidic seven amino acid sequence in its carboxyl terminus. In mammals, the two
      betaIV isotypes (betaIVa and betaIVb) contain that sequence. In order to test the
      application of this hypothesis to mammals, we have examined the expression of
      beta tubulin isotypes in four different ciliated tissues (trachea, ependyma,
      uterine tube, and testis) using isotype-specific antibodies and indirect
      immunofluorescence. We find that betaIV tubulin is present in all ciliated cell
      types examined, but so is betaI tubulin. Taken together with recent studies that
      show that betaI and betaIV tubulin are both present in the cilia of vestibular
      hair cells, olfactory neurons, and nasal respiratory epithelial cells, we propose
      that both betaI tubulin and betaIV tubulin may be required for axonemal
      structures in mammals.

PMID- 12789666
TI  - Association of life events and psychosocial factors with early but not late onset
      depression in the elderly: implications for possible differences in aetiology.
AB  - BACKGROUND: Depression occurring for the first time in later life (after age 60,
      late onset depression (LOD)) may have a different, more organic, aetiology from
      early onset depression (EOD). We investigated the possible role of life events,
      the presence of a confidante and personality factors in the aetiology of
      depression in the elderly, testing the hypothesis that these factors would be
      associated with EOD but not LOD. METHODS: Subjects consisted of 66 elderly
      patients (aged over 60) with DSM-IV Major depression (30 EOD, 33 LOD; groups
      matched for age) and 38 age and sex matched controls. Life events in the 12
      months prior to onset of depression (or prior to interview for controls) were
      recorded using a previously validated 12-item scale. Personality was assessed
      using the Eysenck Personality Questionnaire (EPQ). RESULTS: Subjects with EOD
      reported having a close confidente significantly less frequently (52%) than
      controls (82%, p < 0.05) or LOD (80%, p < 0.05). Bereavement life events occurred
      significantly more frequently in EOD (52%) than LOD (16%, p < 0.01) and were also
      more frequent in controls (42%) than LOD (p < 0.05). Higher EPQ 'extraversion'
      and 'neuroticism' were found in both EOD and LOD compared to controls, with no
      differences between EOD and LOD. CONCLUSIONS: LOD was associated with fewer
      bereavement life events and more frequent presence of a confidente than EOD. This
      supports a greater role for psychosocial factors in the aetiology of EOD and
      different, probably neurobiological, factors in LOD. Personality attributes may
      have a greater relevance for both EOD and LOD than previously recognized.

PMID- 12789667
TI  - Apathy and cognitive performance in older adults with depression.
AB  - OBJECTIVES: Recent studies have linked apathy to frontal lobe dysfunction in
      persons with dementia, but few studies have explored this relationship in older,
      depressed persons without dementia. We examined the association between apathy
      and cognitive function in a group of older persons with major depression using
      standardized neuropsychological tests. We hypothesized that presence of apathy in
      depression is associated with poorer frontal executive performance. METHODS: We
      analyzed data from 89 older adults with major depression. We defined apathy using
      four items from the Hamilton Psychiatric Rating Scale for Depression which
      reflect the clinical state of apathy, including 'diminished work/interest,'
      'psychomotor retardation,' 'anergy' and 'lack of insight.' RESULTS: Apathy most
      strongly correlated with two verbal executive measures (Stroop C and FAS), a
      nonverbal executive measure (Wisconsin Card Sorting Test-Other Responses), and a
      measure of information processing speed (Stroop B). Apathy was not associated
      with age, sex, education, medical illness burden, Mini-Mental State Examination
      score and Full Scale IQ score. Stepwise regression analyses of significant
      cognitive tests showed that apathy alone or apathy plus depression severity, age,
      or education accounted for a significant amount of the variance. CONCLUSIONS: The
      results of this study provide support for an apathy syndrome associated with
      poorer executive function in older adults with major depression.

PMID- 12789668
TI  - Clinical and phenomenological comparisons of delusional and non-delusional major
      depression in the Chinese elderly.
AB  - OBJECTIVE: Distinct clinical entities, with and without delusions, have been
      reported for depressed patients. This study explores the clinical and
      phenomenological aspects of delusional and non-delusional major depression in
      elderly Chinese patients. METHODS: A total of 156 depressed patients (105 males
      and 51 females) admitted to our geriatric psychiatry ward were investigated.
      Sociodemographic and clinical characteristics were compared between patients
      divided into two groups-according to presence or absence of delusions. RESULTS:
      On admission, higher risk of suicide attempt, higher chance of guilt feelings,
      and greater daily functional impairment were observed for the deluded group.
      Further, the score of Hamilton Depression Rating Scale was higher and the score
      of Mini-Mental State Examination was lower for delusional depressives.
      CONCLUSION: Our findings were grossly concordant with previous Western reports,
      and highlight the importance of identifying the delusional subgroup of depressive
      patients because of the higher risk of suicide attempt.

PMID- 12789669
TI  - Use of constraints and surveillance in Norwegian wards for the elderly.
AB  - OBJECTIVE: To describe the use of constraints and surveillance and their
      correlates in a nationwide sample of wards in institutions for the elderly in
      Norway. METHODS: Questionnaires were sent to 975 institutions and returned by 623
      (64%) with 1398 wards. The wards' head nurses were asked whether any patient was
      currently subjected to physical restraints, electronic surveillance, force or
      pressure in medical examination or treatment, and force or pressure in ADL. The
      reporting of constraints was found reliable. RESULTS: In all, 79% of the head
      nurses reported daily or occasional use of constraints in their wards. Most
      frequently reported were force or pressure in the performing of activities of
      daily living (reported by 61%, 95% Confidence Intervals (CI) 59-64), use of force
      or pressure in medical treatment or examination (49%, 95% CI 47-53) and use of
      physical restraints (38%, 95% CI 36-41). Electronic surveillance was used less
      frequently (14%, 95% CI 13-16). All classes of constraints, except physical
      constraints, were used significantly more frequently in special care units for
      persons with dementia than in ordinary nursing home units. The methodology does
      not allow conclusions to be drawn regarding the role of ward size and person
      characteristics. The staffing was unrelated to the use of constraints which
      varied significantly across the counties. CONCLUSION: Constraints are widely used
      in Norwegian institutions for the elderly. A different pattern in use of
      constraints was found between special care units for demented patients and
      ordinary units in nursing homes.

PMID- 12789670
TI  - Screening for late life depression: cut-off scores for the Geriatric Depression
      Scale and the Cornell Scale for Depression in Dementia among Japanese subjects.
AB  - BACKGROUND: Proper screening of depression among older adults depends on accurate
      cut-off scores. Recent articles have recommended the Geriatric Depression Scale
      (GDS) and the Cornell Scale for Depression in Dementia (CSDD) for this screening.
      However, there has been no investigation of the sensitivity and specificity of
      either scale using Japanese subjects. The purpose of the present study was to
      identify appropriate GDS and CSDD cut-offs for Japanese older adults. METHODS:
      The GDS and the CSDD were interview-administered to nondepressed Japanese older
      adults (n = 74) and to Japanese older adults with a SCID-IV diagnosis of major or
      minor depression (n = 37). Depressed subjects were also administered the Hamilton
      Depression Rating Scale (HDRS). Data were also collected on demographic
      variables, mental status, health status, and medication use. RESULTS: ROC curve
      analysis identified a cut-off score of 6 for the GDS which had a sensitivity of
      0.973, a specificity of 0.959, a False Positive Rate (FPR) of 0.894, and a False
      Negative Rate (FNR) of 0. A cutoff score of 5 for the CSDD yielded a sensitivity
      of 1, a specificity of 0.919, a FPR of 0.942, and a FNR of 0. Comparisons
      indicate current HDRS cut-offs may overlook subthreshold depression. The GDS cut
      off score identified among Japanese subjects was the same as that reported for
      Western subjects. CONCLUSIONS: Due to the substantial prevalence of psychiatric
      disorders found in false-negative subjects, the above cut-off scores were chosen
      to optimize the potential for true positives. These scores are recommended for
      alerting physicians and other caregivers as to when more intensive depression
      evaluation is needed.

PMID- 12789671
TI  - Geriatric depression in Nigerian primary care attendees.
AB  - OBJECTIVE: To determine the rate and correlates of geriatric depression in two
      primary care facilities within a teaching hospital in Nigeria. METHOD: 202 older
      people were screened using the Geriatric Depression Scale (GDS). The Geriatric
      Mental State schedule (GMS) was administered to participants who scored above the
      cut-off on the GDS in order to assess psychopathology. Diagnosis of depression
      was based on ICD-10 criteria as well as the GMS-AGECAT program. RESULTS: The rate
      of geriatric depression in primary care was found to be 7.4%. Severe depression
      was only 1.5%. Very low income and subjective report of poor health were
      significantly associated with depression in the cohort. AGECAT recognition of
      depression was comparable to that by the ICD-10 (k = 0.7). CONCLUSION: The study
      is the first known study of geriatric depression in primary care in Nigeria. The
      rates are comparable with rates obtained in other countries. Specific correlates
      of depression in the older Nigerians identified included poor self-assessed
      health and low income.

PMID- 12789672
TI  - Factors associated with antipsychotic drug use in residential care: changes
      between 1990 and 1997.
AB  - BACKGROUND: There is limited information from population-based studies about the
      rates of antipsychotic drug use in residential and nursing homes in the UK, and
      associated adverse effects. OBJECTIVES: To examine the relationship between
      antipsychotic drug prescription, cognitive impairment and disturbed behaviour in
      this population over time, and to identify possible adverse consequences of their
      use. METHODS: Two censuses of the residential and nursing home population aged 65
      years and older in Leicestershire, carried out in 1990 and 1997. A questionnaire
      was completed by care staff for each resident, including information on
      demographic details, physical functioning, cognitive impairment, behaviour
      disturbance, urinary incontinence, falls, mobility, daytime alertness (1997
      only), and prescribed medication. RESULTS: The prevalence of staff-rated moderate
      or severe cognitive impairment increased from 38.0% in 1990 to 44.3% in 1997. The
      prevalence of staff-rated disturbed behaviour decreased from 11.8% in 1990 to
      10.4% in 1997. Cognitive impairment was strongly associated with disturbed
      behaviour in both years. The prescription rate of antipsychotic drugs increased
      from 17.8% in 1990 to 21.9% in 1997. There was no significant change in the
      prescription rates to cognitively impaired residents between 1990 and 1997 (29.1%
      vs 30.7%). In residents without cognitive impairment, the prescription rate rose
      from 10.7% to 15.0%. Antipsychotic drug use was independently associated with:
      younger age, type of home (1990 only), cognitive impairment, offensive behaviour,
      lower ADL dependency (1990 only), antidepressant drug use, reported urinary
      incontinence and greater mobility. There was no association with increased
      liability to falls or drowsiness. In the cognitively unimpaired residents,
      antipsychotic drug use was not associated with urinary incontinence in 1997, and
      there was an association with increased drowsiness in that year. CONCLUSIONS: The
      only significant change in antipsychotic drug prescribing practice in this
      population over the period covered by this study was an increase in the
      prescription rate in cognitively unimpaired residents in 1997, possibly related
      to mental hospital closures. Urinary incontinence was the principal adverse
      effect of antipsychotic drug use observed in the group as a whole. Changes in the
      adverse effects associated with antipsychotic drug use may be a function of the
      increasing frailty.

PMID- 12789673
TI  - Bright light treatment improves sleep in institutionalised elderly--an open
      trial.
AB  - STUDY OBJECTIVES: This study evaluates the effects of bright light therapy among
      demented nursing home patients with sleep disturbances. DESIGN AND SETTING: 11
      nursing home patients with actigraphically measured sleep efficiency below 85%
      took part in an open, non-randomised study where the subjects served as their own
      control. INTERVENTION: After two weeks of baseline measurements and two weeks of
      pretreatment measurements, patients received bright light exposure 2 h/day within
      the period 08:00-11:00 for two weeks. MEASUREMENTS AND RESULTS: Sleep-wake
      patterns during the 24-h day were evaluated by nursing staff ratings and wrist
      worn motor activity devices (actigraphs). Sleep improved substantially with
      bright light exposure. Waking time within nocturnal sleep was reduced by nearly
      two h, and sleep efficiency improved from 73% to 86%. Corresponding improvements
      were found in nursing staff ratings. Effects were consistent across subjects.
      CONCLUSIONS: The findings add further evidence of the effectiveness of morning
      bright light exposure in the treatment of disturbed sleep among demented nursing
      home patients.

PMID- 12789674
TI  - Delusions of Japanese patients with Alzheimer's disease.
AB  - BACKGROUND: Delusions constitute one of the most prominent psychiatric
      complications in Alzheimer's disease (AD). However, there is little consensus of
      the prevalence and associated factors for delusions in AD. AIMS: To reveal the
      characteristics of delusions among Japanese patients with AD. METHOD: 112
      consecutive patients with AD were recruited over a one year period and
      administered the Neuropsychiatric Inventory (NPI). RESULTS: Delusions were
      present in 53 patients (47.3%). Delusions of theft were the most common type of
      delusion (75.5% of patients with delusions), followed by misidentification
      delusions and delusions of suspicion. More hallucination, agitation, and female
      gender were found in the delusions group. CONCLUSIONS: The authors found a high
      frequency of delusions, particularly of delusions of theft and suggested that
      gender was associated with the expression of delusions in Japanese patients with
      AD.

PMID- 12789675
TI  - Recent trends in elderly suicide rates in a multi-ethnic Asian city.
AB  - BACKGROUND: There are a few reports on the trends of elderly suicide rates in
      western countries but none from Asian countries. OBJECTIVES: To describe the
      trends of elderly suicide rates of Chinese, Malays and Indians in Singapore from
      1991 to 2000. DESIGN: Data obtained from the National Department of Statistics
      were used in the analysis of sex- and age-standardized suicide rates and relative
      risks. RESULTS: Overall, the suicide rates for the elderly showed a decline from
      40.1 per 100,000 in 1990 to 17.8 per 100,000 in 2000, with the most pronounced
      decline occurring from 1995 to 2000. The suicide rate for elderly Chinese was at
      a peak of 52 per 100,000 in 1995 and declined to 20 per 100,000 in 2000. The
      rates for elderly Malays were consistently low at 2.2 per 100,000 for the 10
      years; for elderly Indians the rates were between the other two ethnic groups.
      CONCLUSION: In the 10-year period, the elderly suicide rates in Singapore
      declined markedly, especially for elderly Chinese.

PMID- 12789676
TI  - Late-onset auditory hallucinations treated with cognitive behaviour therapy.

PMID- 12789677
TI  - The influence of zinc on the uptake of vitamin B12 by the cerebrospinal fluid.

PMID- 12789678
TI  - A model to classify the sedative load of drugs.

PMID- 12789679
TI  - Suicidal ideation and frontal lobe dysfunction: a study examining the
      relationship between clinical frontal lobe tests depression and suicidal
      ideation.

PMID- 12789680
TI  - Somatic symptoms among older depressed primary care patients.

PMID- 12789681
TI  - Long term safety and efficacy of donepezil in the treatment of dementia in
      Alzheimer's disease in adults with Down syndrome: open label study.

PMID- 12789682
TI  - SSRIs in the treatment of depression in Parkinson's disease.

PMID- 12789683
TI  - Rivastigmine in prevention of delirium in a 65 years old man with Parkinson's
      disease.

PMID- 12789684
TI  - Time waits for no man.

PMID- 12789685
TI  - The Confusion Assessment Method (CAM).

PMID- 12789687
TI  - Cholecystokinin antagonists: pharmacological and therapeutic potential.
AB  - Cholecystokinin (CCK) is a regulatory peptide hormone, predominantly found in the
      gastrointestinal tract, and a neurotransmitter present throughout the nervous
      system. In the gastrointestinal system CCK regulates motility, pancreatic enzyme
      secretion, gastric emptying, and gastric acid secretion. In the nervous system
      CCK is involved in anxiogenesis, satiety, nociception, and memory and learning
      processes. Moreover, CCK interacts with other neurotransmitters in some areas of
      the CNS. The biological effects of CCK are mediated by two specific G protein
      coupled receptor subtypes, termed CCK(1) and CCK(2). Over the past fifteen years
      the search of CCK receptor ligands has evolved from the initial CCK structure
      derived peptides towards peptidomimetic or non-peptide agonists and antagonists
      with improved pharmacokinetic profile. This research has provided a broad
      assortment of potent and selective CCK(1) and CCK(2) antagonists of diverse
      chemical structure. These antagonists have been discovered through optimization
      programs of lead compounds which were designed based on the structures of the C
      terminal tetrapeptide, CCK-4, or the non-peptide natural compound, asperlicin, or
      derived from random screening programs. This review covers the main
      pharmacological and therapeutic aspects of these CCK(1) and CCK(2) antagonist.
      CCK(1) antagonists might have therapeutic potential for the treatment of
      pancreatic disorders and as prokinetics for the treatment of gastroesophageal
      reflux disease, bowel disorders, and gastroparesis. On the other hand, CCK(2)
      antagonists might have application for the treatment of gastric acid secretion
      and anxiety disorders.

PMID- 12789686
TI  - Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and
      antiviral agents.
AB  - The sulfonamides constitute an important class of drugs, with several types of
      pharmacological agents possessing antibacterial, anticarbonic anhydrase,
      diuretic, hypoglycemic, and antithyroid activity among others. A large number of
      structurally novel sulfonamide derivatives have ultimately been reported to show
      substantial protease inhibitory properties. Of particular interest are some
      metalloprotease inhibitors belonging to this class, which by inhibiting several
      matrix metalloproteases (MMPs) show interesting antitumor properties. Some of
      these compounds are currently being evaluated in clinical trials. The large
      number of sulfonamide MMP inhibitors ultimately reported also lead to the design
      of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors,
      potentially useful in the treatment of inflammatory states of various types.
      Since both MMPs and TACE contribute synergistically to the pathophysiology of
      many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual
      inhibition of these enzymes emerged as an interesting target for the drug design
      of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were
      recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide
      type may also be useful in the treatment of inflammatory conditions, such as
      emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and
      acute respiratory distress syndrome. Inhibition of some cysteine proteases, such
      as several caspase and cathepsin isozymes, may lead to the development of
      pharmacological agents effective for the management of several diseases, such as
      rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke.
      Another research line that progressed much in the last time regards different
      sulfonamides with remarkable antiviral activity. Some clinically used HIV
      protease inhibitors (such as amprenavir) possess sulfonamide moieties in their
      molecules, which are critical for the potency of these drugs, as shown by means
      of X-ray crystallography, whereas a very large number of other derivatives are
      constantly being synthesized and evaluated in order to obtain compounds with
      lower toxicity or augmented activity against viruses resistant to the such first
      generation drugs. Other viral proteases, such as those isolated from several
      types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus
      to more effective classes of antiviral drugs.

PMID- 12789688
TI  - Recent advances in de novo design strategy for practical lead identification.
AB  - De novo design programs such as LEGEND, LUDI, and LeapFrog can identify novel
      structures that are predicted to fit the active site of a target protein.
      However, in the conventional de novo design strategy, the output structures
      obtained from the programs can be problematic with regard to synthetic
      accessibility and binding affinity prediction. Thus it has been practically
      difficult to obtain novel lead compounds that are appropriate for medicinal
      chemists through the de novo design strategy. Since the late 1990s, several new
      strategies for lead identification have been reported and the successful examples
      have been disclosed. One of the strategies is validation of small fragments,
      which can be substructures of de novo ligands, by using NMR, X-ray, or MS
      spectra. Another method is prioritization of output structures obtained from de
      novo design programs by chemical accessibility. This review describes these new
      strategies with practical applications and future perspectives of de novo design.

PMID- 12789689
TI  - Platinum-based anticancer agents: innovative design strategies and biological
      perspectives.
AB  - The impact of cisplatin on cancer chemotherapy cannot be denied. Over the past 20
      years, much effort has been dedicated to discover new platinum-based anticancer
      agents that are superior to cisplatin or its analogue, carboplatin. Most
      structural modifications are based on changing one or both of the ligand types
      coordinated to platinum. Altering the leaving group can influence tissue and
      intracellular distribution of the drug, whereas the carrier ligand usually
      determines the structure of adducts formed with DNA. DNA-Pt adducts produced by
      cisplatin and many of its classical analogues are almost identical, and would
      explain their similar patterns of tumor sensitivity and susceptibility to
      resistance. Recently some highly innovative design strategies have emerged, aimed
      at overcoming platinum resistance and/or to introduce novel mechanisms of
      antitumor action. Platinum compounds bearing the 1,2-diaminocyclohexane carrier
      ligand; and those of multinuclear Pt complexes giving rise to radically different
      DNA-Pt adducts, have resulted in novel anticancer agents capable of circumventing
      cisplatin resistance. Other strategies have focused on integrating biologically
      active ligands with platinum moieties intended to selectively localizing the
      anticancer properties. With the rapid advance in molecular biology, combined with
      innovation, it is possible new Pt-based anticancer agents will materialize in the
      near future.

PMID- 12789691
TI  - Community registered design.

PMID- 12789692
TI  - The Dunlop phenomena: a lesson in risk management from an unlikely source.
AB  - Modern production processes are designed to minimise chances of error and poor
      judgement, yet sometimes events occur that initially seem trivial, but ultimately
      prove fatal. In these circumstances, associations between cause and effect can
      become distorted and are often difficult to overcome.

PMID- 12789693
TI  - The effect of gamma irradiation on thermoplastic copolyesters.
AB  - Gamma irradiation affects colour, most notably b, and total transmittance of all
      of the copolyesters used in this study. The changes in colour and total
      transmittance increase with increasing dose level and CHDM content of the
      copolyester. These changes are only temporary and decay with time after
      sterilisation. At the highest dose level, all of the resins showed a slight
      decrease in molecular weight. Small changes in mechanical properties can be
      attributed to physical ageing that occurs at the slightly elevated temperatures
      associated with gamma irradiation. The mechanical properties are, however, stable
      after irradiation indicating no continued effects of the sterilisation process.

PMID- 12789694
TI  - Practical experience of microbiological validation of sterilisation.
AB  - The addition of the VDmax method provides manufacturers with a choice of three
      microbiological validation methods to substantiate a 25 kGy sterilisation dose.
      This article reports on experiences of applying these methods and suggests ways
      to handle difficult products.

PMID- 12789695
TI  - Innovate to speculate.
AB  - The medical device industry can learn from consumer product manufacturers in
      other industries about how to commercially exploit technology in ways that engage
      and excite consumers. This article explores the designer's contribution.

PMID- 12789696
TI  - Change in FDA stance on Part 11 Requirements.
AB  - The United States Food and Drug Administration (FDA) has decided to reexamine its
      regulations for electronic records and signatures, and during this process, to
      reduce the enforcement of some of the provisions of the regulations. This article
      discusses FDA's decision and the content of its related, recently issued guidance
      document.

PMID- 12789697
TI  - Techniques for laser welding polymeric devices.
AB  - Recent advances in laser techniques mean that lasers are now being considered as
      an alternative to vibration, ultrasonic, dielectric, hot plate or hot bar
      welding, and adhesive bonding of plastics. The techniques required to put laser
      welding methods into practice are described for medical devices, tubular systems,
      films and synthetic fabrics.

PMID- 12789698
TI  - Life-cycle management: a long-term challenge.
AB  - With some electronics components being withdrawn after only two years, life-cycle
      management is becoming a key strategic issue for users and manufacturers of
      electromedical equipment. This article describes some approaches to tackling the
      challenge.

PMID- 12789699
TI  - The impact of FDA reform.
AB  - The changes introduced by the Medical Device User Fee and Modernisation Act
      should ensure a timely and effective review process. The impact of some of the
      reforms is discussed here.

PMID- 12789700
TI  - Opportunities with thermoplastics.
AB  - Whether as substitutes for glass and metal, or completely novel injection moulded
      applications, engineering polymers offer a range of opportunities for developing
      cost-effective, safe and smart medical devices.

PMID- 12789701
TI  - Interview with David L. Bernd, FACHE, CEO, Sentara Healthcare, Norfolk, Virginia.
      Interview by Kyle L. Grazier.

PMID- 12789702
TI  - Building job security: strategies for becoming a highly valued contributor.

PMID- 12789703
TI  - The value of market research.

PMID- 12789704
TI  - A profile of hospital acquisitions.
AB  - The number of hospitals acquired by hospital systems has declined from 99
      facilities in 1996 to less than 63 facilities between 1999 and 2000. We evaluated
      the market, operating and organizational factors, and their relationship to these
      hospital acquisitions that occurred during this period of decline. We found that
      acquired hospitals, on average, operated at a loss, incurred higher debt levels,
      and were more likely to be located in markets with a large number of health
      maintenance organizations. Older, for-profit hospitals with fewer occupied beds
      were also likely targets for hospital acquisitions.

PMID- 12789705
TI  - Physicians and hospital managers as cofiduciaries of patients: rhetoric or
      reality?
AB  - The reality of physicians and hospital managers as cofiduciaries of patients is
      of vital importance today. In this article we develop the concept of physicians
      as fiduciaries of patients based on the work of John Gregory and of hospitals as
      fiduciaries of patients based on the work of Thomas Percival to supplement the
      recent literature on organizational ethics in healthcare. To be a fiduciary of
      patients means that (1) one possesses expert knowledge and skills on how to
      protect and promote the health-related interests of patients and (2) one is
      committed to using that expertise primarily for the benefit of the patient and to
      making self-interest a systematically secondary consideration. This concept is
      accepted in contemporary medical ethics and law (McCullough and Chervenak 1994).
      We identify two core virtues--diffidence and compassion--as vital to the
      fiduciary role. We use these virtues to develop preventive ethics strategies for
      dealing with two major problems in physician-hospital administrator interactions,
      what we call strategic procrastination and strategic ambiguity. The main
      preventive ethics response to both strategic procrastination and strategic
      ambiguity is to point them out when they occur and to emphasize that they
      compromise cofiduciary responsibility. As a preventive ethics response to
      strategic procrastination, physicians and managers should provide role models of
      accountability and change policy and practice in a timely manner when
      intellectually obligated to do so. As a preventive ethics response to strategic
      ambiguity, physicians and managers should be role models of transparency by being
      explicit in their communications.

PMID- 12789706
TI  - Organizational downsizing: a review of literature for planning and research.
AB  - The use of downsizing as management's strategic response to environmental and
      institutional changes is prevalent in all U.S. industries, including healthcare.
      The popular and research literature is inundated with reports on companies
      undergoing various stages of restructuring, which often include one or more staff
      reductions. This article provides a review of downsizing literature published
      from 1985 to 2002. Although the findings and conclusions of these articles are
      generally inconsistent, the prevailing opinion is that for downsizing to be
      successful, effective planning must occur long before, during, and after
      downsizing. Additionally, a downsizing plan should be included in the strategic
      management plan of all organizations, regardless of whether they plan to downsize
      or not. By including such a plan, the organization will be better prepared to
      begin the staff-reduction process should it be forced to do so in response to
      environmental changes. Finally, providing ample support and protection for staff
      is key to the organization's recovery and growth. The lessons provided in this
      literature review should assist healthcare managers in deciding how to plan and
      structure potential staff reductions.

PMID- 12789707
TI  - Development of an inpatient rehab facility in an urban safety-net hospital.

PMID- 12789708
TI  - Evidence and the future of medicine.
AB  - For the foreseeable future, the rapid influx of information from sequencing the
      human genome will raise to a still higher level the complexity of scientific and
      ethical issues confronting the practice of medicine. Sustained attention to the
      nature and quality of medical evidence and the extent of medical uncertainty is
      thus important for all concerned--health care providers, policy makers, the
      media, and the general public. The situation poses a special challenge for
      educators. This article presents the author's Ethics of Evidence, an approach for
      dealing with the uncertainties of medicine in the full context of contemporary
      culture. Meant to be of service to all of society, the Ethics of Evidence can be
      symbolized by a lighthouse--a beacon to warn of danger and to show the way. It is
      illustrated here by the example of hypertension, a medical condition afflicting
      tens of millions of Americans.

PMID- 12789709
TI  - The use of placebo interventions in medical practice--a national questionnaire
      survey of Danish clinicians.
AB  - The authors sent a questionnaire to 772 randomly selected Danish clinicians and
      asked them about their use of placebo interventions. Sixty-five percent
      responded. Among the general practitioners, 86% (95% confidence interval 81-91)
      reported to have used placebo interventions at least once, and 48% (41-55) to
      have used placebo interventions more than ten times, within the last year.
      Hospital-based doctors and private specialists reported to have used placebo
      interventions less frequently (p < .001). The most important reason for the use
      of placebo interventions was to avoid a confrontation with the patient. Typical
      placebos were antibiotics for viral infections. Approximately 30% (28-36) of the
      clinicians believed in an effect of placebo interventions on objective outcomes,
      and 46% (42-50) found clinical placebo interventions generally ethically
      acceptable.

PMID- 12789710
TI  - Context effects. Powerful therapies or methodological bias?
AB  - This article provides an analysis of the way in which placebo effects could be
      investigated and taken into account, supported by a description of some of the
      major articles that have been published on this topic. Based on conceptual,
      theoretical, and methodological issues, the authors highlight some of the reasons
      for current controversies regarding the nature of placebo effects. They suggest
      the use of the term context effects to overcome some of the negative connotations
      associated with the term placebo and to highlight the therapeutic nature of the
      health care context, and they present the major findings and limitations from
      their systematic review of the therapeutic effects of health care interactions.
      Recommendations for future research are proposed.

PMID- 12789711
TI  - Measurement in abstinence education. Critique and recommendations.
AB  - The purpose of this article is to identify, assess, and offer solutions to common
      measurement errors found in sexual abstinence education evaluation. A critical
      review of the methodology of adolescent sexuality research was performed. "Gold
      standards" of their measurement strategy were derived and applied against 14
      selected studies. Many of the articles reviewed had substantial limitations in
      their measurement strategies. However, several articles demonstrated excellence
      and serve as models for future efforts. Sexual abstinence education evaluation is
      plagued by the inherent weaknesses of self-report and health outcome measures.
      However, with careful adherence to the gold standards proposed, it is possible to
      limit the threat from these weaknesses, maximizing the benefit of self-report
      surveys and county-level health indicators.

PMID- 12789712
TI  - Evaluability assessment. A catalyst for program change and improvement.
AB  - Using a local cross-cultural health service program as a framework, the authors
      describe the process of an evaluability assessment (EA) and illustrate how it can
      be a catalyst for program change. An EA is a process that improves evaluation.
      The key product was a logic model, which traces the links between objectives,
      activities, and outcomes. Four key insights emerged. First, the distinction of
      who was included and excluded in the target population, originally ambiguous, was
      clearly defined. Second, through the development of the logic model, staff
      members were able to analyze their goals and assumptions and critically explore
      possible gaps between expected outcomes and activities. Third, the EA enabled
      reflection on and clarification of both process and outcome measures. Finally,
      global goals were pared down to better match the project capacity. Developing an
      evaluability assessment was a cost-effective way to collaborate with staff to
      develop a clearer, more evaluable project.

PMID- 12789713
TI  - Toward validation of an assessment tool designed to measure medical students'
      integration of scientific knowledge and clinical communication skills.
AB  - This article reports on a study undertaken to validate an assessment tool of
      medical students' ability to integrate clinical skills and scientific knowledge
      within the patient encounter. One hundred forty first-year medical students at
      the State University of New York at Buffalo examined a standardized patient with
      either acute lower back pain or gastroesophageal reflux disease (GERD). Forty
      eight clinical exams were evaluated by two raters to test the interrater
      reliability of the instrument. Results were promising but mixed. The tool
      displayed high internal consistency. However, results from a generalizability
      study indicated that a significant amount of variance in student scores was due
      to faculty raters. It is recommended that future studies undertake a training
      workshop for raters and examine different cases in an effort to expand the
      flexibility of the instrument.

PMID- 12789714
TI  - AANN and ABNN--family or friends?

PMID- 12789715
TI  - A lot of banter about the nursing shortage these days.

PMID- 12789716
TI  - Defining neuroscience nursing practice: the 2001 role delineation study.
AB  - Studies that provided a blueprint for the Certified Neuroscience Registered Nurse
      (CNRN) examination were conducted in 1987, 1992, and 1997. In 2000, the American
      Board of Neuroscience Nursing (ABNN) formed a task force to re-examine the
      previous role delineation survey, obtain information to define current
      neuroscience nursing practice, and provide content validity for future CNRN
      examinations. Previous role delineation studies conducted by ABNN and a review of
      the literature provided the background for the study. The theoretical framework
      was the Nursing Intervention Classification (NIC) taxonomy and the methodology
      was a survey design. Computer Adaptive Technologies, Inc. (CAT), assisted the
      task force with survey development and data analysis. The survey, a three-part
      questionnaire, was mailed to 1,505 CNRNs and returned by 453 participants.

PMID- 12789717
TI  - Complex regional pain syndrome--type I: research relevance, practice realities.
AB  - Because complex regional pain syndrome--type I usually occurs following minor
      trauma, clients will most likely be encountered in community settings. Nurses
      will come into contact with them as family members, friends, neighbors, and
      coworkers. It is important that nurses become knowledgeable about this syndrome
      to assist in early recognition, diagnosis, and treatment. The latest research
      findings have relevance for current practice, but many questions remain
      unanswered.

PMID- 12789718
TI  - The educational needs of caregivers of stroke survivors in acute and community
      settings.
AB  - Stroke is a major cause of chronic illness in Australia, where it is estimated
      that between 200,000 and 250,000 people live with disabilities due to stroke.
      Given stroke's effect on survivors and the accompanying burden on caregivers,
      attention should be given to addressing the needs of caregivers of stroke
      survivors because they are central to supporting survivors living in the
      community. Research has shown that the information needs of caregivers are not
      being met across healthcare settings. Thus, some attention must be given to the
      development of educational materials that address caregiver needs. In this study
      we interviewed caregivers to determine their perspectives on support and
      educational needs at two different stages in the recovery of the stroke survivor:
      the acute hospital and the community. Despite a high level of uncertainty among
      caregivers in the acute and community settings, limited information was provided
      to assist them in their new role. A multifaceted approach would involve the
      development and implementation of specifically designed educational materials for
      caregivers; the use of a tool such as a patient-held record to assist in and
      improve the continuity and communication of care, and the provision of ongoing
      support from a stroke nurse practitioner who would follow stroke survivors from
      the acute setting to the community. This approach should be evaluated so that the
      important issue of addressing caregiver needs is given its due attention.

PMID- 12789719
TI  - Broadening the understanding of injury prevention: a case study.
AB  - The death or injury of a loved one is tragic, especially if that injury could
      have been prevented. Programs to reduce the incidence and severity of
      neurological trauma are traditionally driven by injury statistics, and the
      literature on neurological injury prevention often fails to capture individual
      experiences. Understanding community members' concerns about injury and safety
      efforts can move injury-prevention programs to a new level by assessing injury
      related beliefs and refining interventions suited to the community. Pediatric
      injury is an especially complex problem that is influenced by developmental,
      environmental, sociopolitical, economic, geographic, parental, and child-related
      factors. Recognition of injury as a public health concern supports updating
      program development. The following case study, based on an in-depth parent
      interview, offers a unique perspective on pediatric injury. The audiotaped
      interview was transcribed verbatim following qualitative guidelines. Three main
      themes emerged from the analysis: (a) sources of parental concern for children's
      safety, (b) private versus public safety influences, and (c) behaviors making
      children vulnerable to injury. As this case study illustrates, parents may
      consider children susceptible to injury as a result of factors often not
      considered by injury prevention programs, for example, being "injury prone."
      Parents also have access to resources, grandparents, for example, not typically
      considered when programs are marketed. The challenge is to identify how programs
      become an accepted public safety influence and to address real-life parental
      concerns.

PMID- 12789720
TI  - Adolescents' lived experience of epilepsy.
AB  - To improve the well-being of adolescents with epilepsy, research is needed on how
      adolescents cope. In this study, Lazarus' model of stress and coping and
      Antonovsky's Theory of Sense of Coherence were used as the theoretical framework.
      The aim was to describe the lived experience of adolescents with epilepsy and
      their coping skills. The participants were 13-19 years old with an epilepsy
      diagnosis but without mental retardation or cerebral palsy. The study was
      performed in southern Sweden at the pediatric department of a university
      hospital. Semistructured and open-ended interviews were conducted with 13
      adolescents. The transcripts were analyzed with manifest and latent content
      analysis. All the adolescents had developed strategies to cope with the emotional
      strains caused by epilepsy. They experienced strains from the seizures,
      limitation of leisure activities, side effects of medication, and feelings of
      being different. The coping strategies described were finding support, being in
      control, and experimenting.

PMID- 12789721
TI  - Metastatic compression fractures--vertebroplasty for pain control.
AB  - Quality of life issues remain at the forefront for individuals with life
      threatening disease, such as metastatic cancer. The pain of metastatic bone
      cancer can severely hamper an individual's quality of life. Percutaneous
      vertebroplasty offers a minimally invasive way to reinforce bony elements,
      provide substantial improvement in pain control, allow for mobilization, and
      overall improve quality of life in these patients.

PMID- 12789722
TI  - Scientific integrity--the cornerstone of knowledge.
AB  - In the past, nurses often found themselves pressured within complex social
      interactions in the research environment that often overshadowed their advocacy
      role for the patient (Davis, 1989). With the recent emphasis on enforcing
      adequate protections for participants in research, nurses need to feel free to
      act as sentient beings with a conscience and a strong commitment to their
      patients. It is only through this advocacy role that scientific misconduct can be
      reduced and research integrity upheld.

PMID- 12789723
TI  - Sanazole as a sensitizer of hypoxic cells with radical radiation in the treatment
      of advanced cancer of cervix an Indian experience.
AB  - AK-2123, is a nitrotriazole with a potential to sensitize hypoxic tissue to
      radiation. Cancer of cervix in advanced stages are predominantly treated with
      radiation. These are the tumours which harbour a large hypoxic core. This is an
      Indian experience of the multicentric trial. Patients were randomized to control
      and AK-2123 arm. 49 patients were randomized to each group. Patients received
      external radiation with telecobalt to a dose of 50 Gy in five weeks. Those in the
      study arm received 600 mg/m2, on alternate days. The patients were further
      treated with intracavitory radiation a dose of 20 Gy. The total dose of 70 Gy was
      achieved. Patients in the study arm had a complete response of 71.43% (35 of 49)
      while only 21 of 49 (42.86%) responded in the control group. The overall survival
      at two years was 72.2% for the study group and 32.43% for control. Neuropathy, a
      drug related toxicity was transient except, in one patient, which has persisted.
      AK-2123, has shown significant radiation sensitizing potential.

PMID- 12789724
TI  - Triangular approach for the diagnosis of monoclonal gammopathy in malignancies.
AB  - Monoclonal Gammopathy (MG) in multiple myeloma (MM) is an established association
      but its occurrence in nonmyelomatous malignancies and other inflammatory
      conditions is still a subject of research. We carried out this study to detect
      monoclonal gammopathy in myelomatous and nonmyelomatous malignancies by adopting
      the triangular approach of correlating radiologic findings, bone marrow studies
      and electrophoretic findings. 200 cases of malignancies (25 cases of multiple
      myeloma and 175 cases of nonmyelomatous malignancies) were studied. Serum and
      urine electrophoresis was carried out in every case and positive cases were
      subjected for typing by immunoelectrophoresis (IEP). The incidence of monoclonal
      gammopathy in nonmyelomatous malignancies was 2.29% (4/175 cases), in epithelial
      malignancies was 0.8% (1/125 cases) and 6% (3/50 cases) in haematological
      malignancies. Though the study sample was small, these interesting findings
      warrant more exhaustive research in this field.

PMID- 12789725
TI  - Renal angiomyolipoma: a clinico-pathological study or eleven cases.
AB  - Retrospective analysis of clinical and histomorphological features and follow up
      of eleven cases of renal angiomyolipoma (AML) encountered during the past twelve
      years at our centre was performed. These included seven female and four male
      patients, nine of them were symptomatic and two were incidentally detected on
      ultrasonography for other reasons. Eight patients had solitary and three had
      bilateral lesions on radiological investigations. None of the three patients with
      bilateral AML had associated tuberous sclerosis, however, a patient with tuberous
      sclerosis, showing solitary lesion on radiological investigation, was detected to
      have multiple lesions on thorough pathological examination of the nephrectomy
      specimen. The surgical treatment comprised of nephrectomy in six cases,
      enucleation in four cases and trueut biopsy in one case. Enucleation of the
      largest lesion was done in all three patients of bilateral AML. The mean follow
      up was of three years. Two patients with bilateral AML had radiological
      progression of size of other lesions, whereas one died due to excessive bleeding
      in the postoperative period. None of the patients had any evidence of recurrence
      or metastasis. Bilateral AML is not always associated with tuberous sclerosis,
      however, in patients with tuberous sclerous thorough sampling of nephrectomy
      specimen is recommended.

PMID- 12789726
TI  - Cytogenetic profile of chronic myeloid leukemias.
AB  - Chronic Myeloid leukemia is a clonal disease of multipotent haematopoietic cells
      associated with specific cytogenetic changes involving a translocation t(9;22)
      (q34:q11), more commonly known as Philadelphia Chromosome (Ph1). A total of 525
      patients with CML (480 adults and 45 children) diagnosed at the Nizam's Institute
      of Medical Sciences, Hyderabad, formed the subjects of this study. Hematological
      investigations were carried out using standard methods. Unstimulated peripheral
      blood samples and/or bone marrow aspirates were used for cytogenetic analysis.
      Hematological evaluation at presentation showed that 435 were in chronic phase,
      36 in accelerated phase and 54 in blast crisis. Chromosomal analysis revealed
      that 86.3% were Ph1 positive and 13.7% Ph1 negative. Additional chromosome
      changes observed during blast crisis included an extra Ph1 chromosome, Trisomy 8
      and Trisomy 19. The results were correlated with survival pattern and prognosis
      of patients following certain treatment protocols.

PMID- 12789727
TI  - Atypical distant metastases from hypopharyngeal cancer.
AB  - Hypopharyngeal squamous carcinoma is an aggressive disease with a high frequency
      of local and distant spread. Distant metastasis is seen more often now because of
      better loco-regional control due to more aggressive multimodal therapy. This
      article reports two cases of unusual metastatic disease from squamous carcinoma
      of pyriform sinus and reviews the metastatic disease in hypopharyngeal squamous
      cancers. The first was a case of metastatic pericardial effusion and the second
      was a metastasis to soft tissues of the scapular region and lung.

PMID- 12789728
TI  - Prosthetic rehabilitation of a patient following maxillectomy with orbital
      exenteration.
AB  - The maxillectomy patient despite the drastic nature of the procedure can often be
      restored to an acceptable aesthetic and functional condition. The treatment of
      maxillectomy patient presents an excellent opportunity for the surgeon and the
      prosthodontist to coordinate their efforts to enhance the patient's
      rehabilitation. This clinical report describes the prosthetic rehabilitation of a
      patient with squamous cell carcinoma of the right maxilla requiring maxillectomy
      with orbital exenteration.

PMID- 12789730
TI  - Primary squamous cell carcinoma of the ovary in a young patient. A case report.
AB  - A case report of a squamous cell carcinoma arising in a dermoid cyst of the ovary
      in a 29 year old patient is presented. Such an occurrence in young patients is
      unusual.

PMID- 12789729
TI  - Carcinoma prostate with penile metastases. A case report.
AB  - Prostatic carcinoma metastasizing to the penis is rare. The prognosis is also
      poor. A case of carcinoma prostate with penile metastases where successful
      palliation was achieved with external radiation therapy is reported.

PMID- 12789732
TI  - Reform of the Mental Health Act: its direction and impact.

PMID- 12789731
TI  - Psoas abscess-like metastasis from transitional cell carcinoma of urinary
      bladder.
AB  - We report a 70-year-old male who presented with gross painless total haematuria
      associated with persistent left hip pain of one month duration. Computerised
      tomography of abdomen revealed a mass on the right lateral wall of urinary and
      abscess like lesion in the left psoas. He underwent transurethral resection of
      bladder tumour and ultrasonographical guided tru-cut biopsy of psoas lesion.
      Histopathology confirmed transitional cell carcinoma with metastasis to left
      psoas muscle. The presentation highlights the clinical and radiological features
      along with review of literature of rare metastatic site from transitional cell
      carcinoma of urinary bladder.

PMID- 12789733
TI  - Irritable bowel syndrome: unravelling the mysteries.

PMID- 12789735
TI  - Infection as a cause of irritable bowel syndrome.
AB  - The normal response to infection, such as vomiting and diarrhoea, is protective
      and beneficial. However, in about 10% of patients these protective changes
      persist and may contribute to the development of post-infective irritable bowel
      syndrome, which may persist for many years. New insights into the pathogenesis of
      this condition suggest novel, effective ways of treatment.

PMID- 12789734
TI  - Brain-gut interaction in irritable bowel syndrome.
AB  - Abdominal pain occurs commonly in irritable bowel syndrome. The mechanism of pain
      is likely to be either peripheral or central sensitization of gut nerves or
      aberrant brain processing. Functional brain techniques are now allowing the study
      of brain-gut interactions.

PMID- 12789736
TI  - Chronic pelvic pain and irritable bowel syndrome.
AB  - This article describes the common association between chronic pelvic pain and
      irritable bowel syndrome. The aim of the diagnosis and management of chronic
      pelvic pain and irritable bowel syndrome is to improve the quality of life of the
      patient. Methods of diagnosis, treatment and overall management for these two
      challenging conditions are outlined in this article.

PMID- 12789737
TI  - Thromboprophylaxis in patients undergoing total hip replacement.
AB  - Venous thromboembolism is a common complication following a hip replacement. It
      was the authors' impression that prophylaxis of deep vein thrombosis has changed
      in recent years. The authors felt that it was important to repeat a survey, done
      in 1997, on the use of thromboembolism prophylaxis among British orthopaedic
      surgeons.

PMID- 12789738
TI  - Use of carvedilol in the treatment of heart failure.
AB  - Carvedilol is a multiple action, non-specific, adrenergic beta-blocker, licensed
      for the treatment of mild, moderate and severe chronic heart failure. This
      article considers the evidence for using beta-blockers in general, and carvedilol
      in particular, in the treatment of heart failure. Evidence suggests that
      carvedilol should be considered as an alternative first-line initiation therapy.

PMID- 12789740
TI  - Acute compartment syndrome: diagnosis and immediate care.
AB  - Acute compartment syndrome is an uncommon but potentially limb-threatening
      condition whose early recognition and treatment can prevent or reduce serious
      complications. Identifying at-risk patients and appropriate investigation is the
      key.

PMID- 12789739
TI  - Oral agents for erectile dysfunction.
AB  - Erectile dysfunction is a common disease affecting the lives of millions of men
      worldwide. Sildenafil was the first oral treatment licensed for male erectile
      dysfunction. However, there are now a number of other options available. In this
      article the currently available oral treatments are reviewed.

PMID- 12789741
TI  - The eye in cardiac and cardiovascular disease.

PMID- 12789742
TI  - An initiative to reform senior house officer training in histopathology.
AB  - Senior house officer schools in histopathology have been established in Leeds,
      Leicester and Southampton, each training six new recruits each year. Nine hours
      of protected teaching time is provided each week giving a ratio of apprenticeship
      learning to formal teaching of 3:1. Evaluations have been very positive. Much of
      this success is attributed to careful planning and adequate funding. This may be
      a useful model for other specialties to follow.

PMID- 12789743
TI  - Tuberculous meningitis with tuberculomata presenting as postpartum pyrexia of
      unknown origin.

PMID- 12789744
TI  - Visceral leishmaniasis misdiagnosed as probable acute lymphoblastic leukaemia.

PMID- 12789745
TI  - A cirrhotic patient with fever and abdominal pain in the presence of ascites.

PMID- 12789746
TI  - Informed consent and junior house officers.

PMID- 12789747
TI  - Antibiotic prescribing must improve.

PMID- 12789748
TI  - Should we treat severe sepsis with activated protein C?

PMID- 12789749
TI  - Cut to the chase.

PMID- 12789750
TI  - The HSJ interview: Dr Evan Harris. Gruel intentions. Interview by Lyn Whitfield.

PMID- 12789751
TI  - PCT merger. Building bridges.
AB  - Primary care trusts can be torn between the need for critical mass and the danger
      of losing local vision and ownership; mergers are politically unpopular and
      fraught with difficulty. A review of Trafford South PCT stakeholders enabled a
      range of organisational models to be tested. The result was the creation of a
      'joint and integrated management structure' for the two Trafford PCTs.

PMID- 12789752
TI  - Clinical IT. Ticker taped.
AB  - Paper-traced records of difficult births can be a poor-quality defence in
      litigation. A newly developed IT system provides an electronic archive of
      clinical data. A further module to provide automatic decision support is under
      evaluation.

PMID- 12789753
TI  - HSJ people. Back in the fold.

PMID- 12789754
TI  - Temporal bone fracture with tympanic membrane perforation and hemorrhage.

PMID- 12789755
TI  - Antrochoanal polyp displacing the uvula and the soft palate.

PMID- 12789757
TI  - Gelfoam injection as a treatment for temporary vocal fold paralysis.

PMID- 12789756
TI  - Tracheoesophageal fistula caused by ingestion of a caustic substance.

PMID- 12789759
TI  - A case of dizziness, headache, aural fullness, and concentration difficulty
      following scuba diving.

PMID- 12789760
TI  - Primary parathyroid hyperplasia.

PMID- 12789758
TI  - Epiphrenic diverticulum.

PMID- 12789761
TI  - How to measure your practice's level of patient satisfaction.

PMID- 12789762
TI  - Treatment of advanced oropharyngeal cancers with chemotherapy and radiation.
AB  - We conducted a retrospective chart review of treatment outcomes in 17 adults who
      had been selected to undergo concomitant chemotherapy and radiation (chemo/XRT)
      for late-stage oropharyngeal cancers. All patients had been treated at the West
      Los Angeles VA Medical Center between March 1, 1998, and Sept. 30, 2000. Nine
      patients had a primary tumor at the base of the tongue, five had a primary tumor
      in the tonsillar area, and three had a tumor that affected both sites. Of this
      group, 15 patients completed one to three cycles of chemo/XRT, and the remaining
      two died during therapy. At the most recent follow-up, 9 of the 17 patients
      (52.9%) were documented to still be alive; seven patients had earlier died as a
      result of their primary tumor or a distant metastasis, and one patient had been
      lost to follow-up after completing treatment. At study's end, the duration of
      post-treatment survival ranged from 2 to 36 months (mean: 12.5). Based on the
      results of our small series, we conclude that chemo/XRT is a valid alternative to
      surgery with postoperative radiation and to radiation alone. Chemo/XRT yields
      acceptable rates of local control and allows for organ preservation with
      tolerable side effects.

PMID- 12789763
TI  - Salivary duct carcinoma of the larynx: report of a rare case.
AB  - Salivary duct carcinomas are primarily high-grade, aggressive malignancies that
      affect men in the fifth and sixth decades of life. These tumors are usually found
      in the major salivary glands; rarely do they originate in the minor salivary
      glands. The distinctive feature of these neoplasms is their remarkable histologic
      resemblance to infiltrating ductal carcinomas of the mammary gland; both types of
      tumor feature epithelial and myoepithelial cells arrayed in solid, papillary, and
      cribriform patterns. To the best of our knowledge, only one case of a primary
      salivary duct carcinoma of the larynx has been previously reported. In this
      article, we describe a new case, and we review the literature on salivary duct
      carcinomas.

PMID- 12789765
TI  - Cystosarcoma phyllodes metastatic to the mandible: report of a rare case and
      literature review.
AB  - Cystosarcoma phyllodes is a rare breast tumor with variable malignant potential.
      Metastasis has been reported in a small percentage of cases. We describe the case
      of a 52-year-old woman who developed a large facial tumor 1 year after she had
      undergone a mastectomy for a rapidly enlarging breast neoplasm. The facial lesion
      was found to be a malignant cystosarcoma phyllodes metastatic to the mandible,
      and the patient died shortly after diagnosis. To our knowledge, this patient
      represents only the third reported case of a phyllodes tumor metastatic to the
      mandible.

PMID- 12789764
TI  - Management of acoustic neuromas in the elderly: retrospective study.
AB  - The wide availability of gadolinium-enhanced magnetic resonance imaging (MRI-Gd)
      has led to the discovery of an increasing number of small and less symptomatic
      acoustic neuromas in elderly patients. We conducted a retrospective study in
      order to obtain data on outcomes and complications associated with different
      management strategies that would be useful in establishing a management
      guideline. We identified 44 patients aged 65 to 77 years with acoustic neuromas
      who had been managed with either surgery or simple observation with MRI-Gd
      imaging. Of the entire group, 36 patients had tumors larger than 1 cm, and they
      underwent surgery (most via the translabyrinthine approach). Complete removal of
      the tumor was achieved in 34 of these patients (94.4%). At the 1-year follow-up,
      grade VI facial nerve paralysis was evident in only two of 35 evaluable patients
      (5.7%). Postsurgical complications occurred in five patients (13.9%), including
      one death. The remaining eight patients had tumors 1 cm or smaller, and they were
      managed with periodic MRI-Gd scanning. At the 5-year follow-up, no tumor growth
      was seen in six of these patients. The other two patients exhibited a tumor
      growth rate of less than 2 mm per year. No patient in the observation group
      required surgical intervention.

PMID- 12789766
TI  - A case of renal cell carcinoma metastatic to the nose and tongue.

PMID- 12789767
TI  - Insular carcinoma of the thyroid.
AB  - Thyroid surgeons are becoming increasingly more aware of a histologically
      distinct subset of thyroid carcinoma whose classification falls between well
      differentiated and anaplastic carcinomas with respect to both cell
      differentiation and clinical behavior. This subtype of tumors has been
      categorized as poorly differentiated or insular carcinoma, based on its
      characteristic cell groupings. Although the differentiation of insular carcinoma
      from other thyroid carcinomas has important prognostic and therapeutic
      significance, relatively little about insular carcinoma has been published in the
      otolaryngology literature. In this article, we describe a new case of insular
      carcinoma and we discuss the findings of our review of the literature. We
      conclude that insular thyroid carcinoma warrants aggressive management with total
      thyroidectomy followed by radioactive iodine ablation of any remaining thyroid
      tissue.

PMID- 12789768
TI  - Subtotal parathyroidectomy: a possible treatment for calciphylaxis.
AB  - Calciphylaxis is a rare disorder in patients with chronic renal failure that is
      characterized by ischemic necrotic skin lesions. The prognosis is grave and
      mortality is high (80%). The precise mechanism of calciphylaxis is still unknown,
      but in addition to chronic renal failure, elevated parathyroid hormone levels
      appear to play a role. The role of parathyroidectomy in treating affected
      patients is questionable. In this article, we describe the case of a patient with
      chronic renal failure who developed rapidly progressive subcutaneous
      calcifications and ulcerations in the lower extremities. These lesions regressed
      following subtotal parathyroidectomy. We also review the literature on
      calciphylaxis, with a focus on treatment options.

PMID- 12789769
TI  - [50 years of the Institute for Research in Pharmacy and Biochemistry].
AB  - After the nationalization of pharmaceutical industry and establishment of the
      United Pharmaceutical Enterprises in 1946, the Research and Control Institute
      (VKU) was established in Prague in 1947 to support the development of research,
      manufacture, and control of drugs. After other measures of nationalization and
      unification of research, in 1951 the research sections of the VKU and the
      pharmaceutical sections of the Research Institute of CCHZ were fused to form the
      Research Institute for Pharmacy and Biochemistry (VUFB). The section the VUFB
      taking care of the quality of production was transformed into the Pharmaceutical
      Control Institute (KUF). Each of the institutes had its own farm for breeding
      experimental animals outside Prague. In 1958, KUF was transformed into the
      Research Institute of Medicinal Plants (VULERO) and later, in 1960, into the
      Research Institute of Natural Substances (VUPL), which eventually fused with VUFB
      in 1967. During the years of increasing activities of VUFB, a chemical pilot
      plant was established in Olomouc, and a department of clinical pharmacology in
      Plzen. Research activities of VUFB were aimed to search for original drugs and to
      develop non-proprietary medicines in the field of the central and vegetative
      nervous systems, blood circulation, inflammatory processes, microbial infections,
      carcinostatic drugs, etc. In natural substances, the greatest attention was paid
      to ergot alkaloids, but the extent of research also included the constituents of
      the poppy, periwinkle, and other plants. An important part of the programme was
      also the breeding and cultivation of selected medicinal plants. The results of
      research were continuously published in both inland and foreign scholarly
      journals and at conferences and congresses. Every year, usually more than 100
      papers were published and 40-50 for patents applications were submitted. The
      activity of the Institute resulted in the production of 30 original substances
      which were introduced into therapeutic practice. Twenty of them are still
      commonly prescribed. Some of these original substances got into foreign markets,
      particularly Prothiaden and Trimepranol represented important exports. In
      addition, 83 non-proprietary drugs were introduced into the inland market.

PMID- 12789770
TI  - [Two-phase semi-solid hydrophilic systems--hydrocreams].
AB  - Production of a drug of good quality in the form of a hydrocream presents a wide
      set of complex problems. Hydrocreams as emulsions of the o/w type form a
      structured system which consists of at least three phases, the dispersed,
      crystalline hydrated, and crystalline gel one. The loading operations of
      manufacturing procedures can negatively affect both the individual components and
      the complex structure of the hydrocream. Due attention must thus be paid to the
      formulation study which together with the conditions of manufacture will ensure
      the production of a drug with required quality indices.

PMID- 12789771
TI  - [Chiral separation of drugs based on macrocyclic antibiotics using HPLC,
      supercritical fluid chromatography (SFC) and capillary electrochromatography
      (CEC)].
AB  - Separation of enantiomers by means of high-performance liquid chromatography
      (HPLC), supercritical fluid chromatography (SFC), and capillary
      electrochromatography (CEC) is of great importance in pharmaceutical analyses. In
      recent years, separation of various types of racemates employs most frequently
      chiral stationary phases based on macrocyclic antibiotics. This class of chiral
      selectors includes vancomycin, teikoplanin, ristocetin A, teikoplanin without
      saccharide components, avoparcin, etc. The review paper describes the properties
      of selected antibiotics, the effect of chromatographic conditions on
      enantioselectivity (effect of the composition of the mobile phase, effect of pH
      of the mobile phase, effect of temperature), and the study of possible mechanisms
      of interaction, which play an important role in the separation of enantiomers.
      Examples of the use of macrocyclic antibiotics in the separation of various
      compounds by means of the HPLC, SFC, and CEC methods follow.

PMID- 12789772
TI  - [Natural substances as chemoprotective agents].
AB  - The fate of xenobiotics in the organism and their toxic or therapeutic influence
      have been under intensive investigation in recent years. The compounds are
      searched for which affect as preventive agents cancerogenesis and other disorders
      caused by procancerogens and pro-mutagens from the environment. The main focus is
      on the compounds able to modulate the activity of enzymes of the Ist and IInd
      phase of xenobiotic detoxication or compounds with antioxidative activity. In the
      following review, compounds of natural origin are presented which possess an
      ability to modulate the processes connected with detoxication of xenobiotics.
      These compounds could be usable as preventive agents against some diseases or as
      supportive pharmaceuticals during chemotherapy.

PMID- 12789773
TI  - [Effect of pilocarpine chloride on pseudoplastic hydrogel].
AB  - Colloidal aqueous dispersions of 2 to 5% (weight) of hydroxypropylmethylcellulose
      (HMPC 4000) yield pseudoplastic mucilages and gels. Rotational viscosimetry in
      the cone-plate arrangement enables rapid and reproducible evaluation of the
      transitional region between pseudoplastic and plastic deformation, characterized
      by Herschel-Bulkley equation. To the traditional Ostwald's two-parameter
      relationship it adds a third one, revealing a deviation from the beginning of the
      coordinates of the rheogram caused by the limiting yield stress. The obtained
      equations make it possible not only to estimate apparent and real viscosity, but
      also the area under the curve of the pseudoplastic rheogram. The actual
      precondition of integration, however, is the estimation of the limiting yield
      stress as the shear rate for the zero shear stress. Experimental estimation of
      the bottom margin for the integration of the area under the curve makes mutual
      comparability of rheograms possible. At a temperature of 32 degrees C, analysis
      of variance demonstrated a significant diminution of this area in the presence of
      about 2% of pilocarpinium chloride.

PMID- 12789774
TI  - [TCL and HPLC separation of positional isomers of alkylester acids of 2-, 3-, 4
      [2-hydroxy-3-[(4-diphenylmethyl) piperazine-1-yl]propoxy]phenylcarbamic acid and
      their lipohydrophilic properties].
AB  - The paper deals with chromatographic separations of newly prepared substances,
      aryloxyaminopropanol derivatives. The derivatives represent three homological
      series of four carbons and four groups of positional isomers (methyl- to butyl-
      in positions 2-, 3, and 4-). Thin-layer adsorption chromatography employed the
      foil Silufol UV 254 as the stationary phase and partition chromatography,
      commercially produced glass plates DC Fertigplatten MERCK RP-8 F254 S. High
      performance liquid chromatography was used to separate positional isomers on the
      column Supelkosil ABZ + PLUS. The mobile phase was methanol and acetonitrile in
      graded rations with water and various flow rates of the mobile phase were tested.
      Partition chromatography, determination of partition coefficient in the system
      octanol-water, and the values of capacity factors k' of the substances was
      employed to evaluate their lipophilicity.

PMID- 12789775
TI  - [Effect of disinfectants on surface hydrophobicity and mobility in Salmonella
      enterica serovar Typhimurium DT104].
AB  - The paper evaluated antibacterial efficacy of 12 disinfectants on the basis of
      quaternary ammonium compounds (KAZ) on the isolates of Salmonella enterica
      serovar Typhimurium of the definitive phage type 104 (DT104). One isolate-
      5551/99--represented the multiresistant phenotype, resistant to ampicillin (A),
      chloramphenicol (C), streptomycin (S), and tetracycline (T). The second isolate-
      577/99--was sensitive to all antibiotics tested. The present study further
      examined the capability of sub-MIC concentrations of disinfectants to intervene
      into surface hydrophobicity and motility of the strains tested. The results
      showed that all disinfectants under study exhibited high antibacterial activity.
      It is of interest that the isolate resistant to antibiotics was more sensitive to
      disinfectants in comparison with the isolate resistant to antibiotics. The most
      effective substances against strain 5551/99 (R-type) were Sokrena, Triquart,
      Hexaquart plus, ID213, and Microbac forte, and those most effective against
      strain 577/99 (S-type) were Benzalkonium chloride and Hexaquart plus (MIC 0.09
      0.19 microliter/ml). Surface hydrophobicity of both tested strains after the
      action of sub-MIC (1/16, 1/8, 1/4 of MIC) of disinfectants was not influenced in
      a more marked way. In the case of strain 5551/99, the highest percentage of
      inhibition of adherence to xylene, to 69.5% versus the control, was produced by
      1/4 of MIC of the substance Triquart and, in the whole concentration range, by
      the substance Microbac forte. After the action of most substances to strain
      577/99, stimulation of adherence took place. Only substance ID213 induced
      inhibition of adherence in the whole concentration range. The salt-aggregative
      capabilities of both strains were not influenced in a more marked way. The only
      exceptions were the action of 1/4 of MIC of the substances Cetrimid, Sokrena,
      ID212, Forten, and 1/8 of MIC of Hexaquart S on strain 577/99, where a decrease
      in hydrophobicity was observed. A moderate inhibition of motility was found after
      the action of 1/4 of MIC of Benzalkonium chloride (to 87.5%) and A.D.L. 007 (to
      85.2%) on strain 5551/99. In the case of sensitive isolate 577/99, the most
      markedly manifested inhibition effect was that of Sokrena within the whole
      concentration range and that of 1/4 of MIC ID213. The results can be used in the
      selection of a suitable disinfectant for decontamination of solid surfaces. The
      effect of substances under study on surface hydrophobicity and motility of the
      important, food-transferred pathogen in the sense of inhibition or stimulation
      points out to intervention into its pathogenic potential.

PMID- 12789777
TI  - [Jaroslav Hladik--a Czech pharmaceutical historian on his jubilee].
AB  - Jaroslav Hladik, who on 12. April 2003 would reach the age of 100 years, started
      his professional career as a pharmacist in different pharmacies, but after
      certain period of interim activities he became a university teacher Associate
      Professor for Pharmaceutical History, founded a pharmaceutical museum, published
      papers on pharmaceutical history, laid the foundations of a centralized
      pharmaceutical book collections, etc. He was successfully active in several
      pharmaceutical university institutions in Prague, Brno, and Bratislava.
      Pharmaceutical history remained his hobby until his death on 1. August 1975. He
      is remembered as a great positive personality of Czech pharmacy.

PMID- 12789776
TI  - [Effect of jasminic acid on production of anthracene derivatives in cultures of
      Rheum palmatum L].
AB  - The process of elicitation makes use of the capacity of plants and plant cells
      cultivated in vitro to react to various stress stimuli by a number of protective
      reactions leading to increased accumulation of secondary metabolites. The
      endogenic signal substances of plant protective reactions include jasminic acid,
      which in the case of exogenous application also acts as an elicitor. The paper
      examined the effect of four concentrations of jasminic acid on the production of
      anthracene derivatives by a three-year-old tissue culture, which was derived from
      the roots of a two-year-old intact plant Rheum palmatum L. (Polygonaceae). The
      culture was cultivated on Murashige-Skoog medium with an addition of 10 mg.l-1 of
      alpha-naphthylacetic acid. The results show that the optimal effect of jasminic
      acid on the production of callus culture was manifested after a 12-hour
      application of the strongest concentration of 5 mM, and on the production of
      suspension culture after a 48-hour application of a concentration of 0.05 mM,
      when the photometric determination according to PhBs 4 demonstrated the maximal
      content of anthracene derivatives (1.26%) and the production was stimulated by
      109% in comparison with the control.

PMID- 12789778
TI  - [Diagnosis-related grey zones].

PMID- 12789779
TI  - [Public health announcement--from talks to plan].

PMID- 12789780
TI  - [Do children need another vaccine?].

PMID- 12789781
TI  - [Albumin, artificial colloids or saline solutions?].

PMID- 12789782
TI  - [We need more psychiatric outpatient clinics, too].

PMID- 12789783
TI  - [Do psychiatric patients receive the correct level of treatment?].

PMID- 12789785
TI  - [Surgical treatment of Meniere's disease].

PMID- 12789784
TI  - [Use of albumin in Norwegian hospitals--changes following the 1998 Cochrane
      report].

PMID- 12789786
TI  - [Socioeconomic conditions and asthma in 4-5-year old children--a cohort study in
      Vesthold].

PMID- 12789787
TI  - [Gastrointestinal stromal tumor].

PMID- 12789788
TI  - [Stress ulcer].

PMID- 12789789
TI  - [More children should be vaccinated against pneumococcal disease].

PMID- 12789790
TI  - [Drug-induced severe jaundice].

PMID- 12789791
TI  - [Congenital melanocytic nevi--what should be said and done?].

PMID- 12789793
TI  - [Use of fluconazole during pregnancy].

PMID- 12789792
TI  - [Cutis marmorata telangiectatica congenita].

PMID- 12789794
TI  - [The hospital--a vulnerable zone].

PMID- 12789795
TI  - [Expected longevity in Europe: increasing gap between east and west].

PMID- 12789796
TI  - [A tiger leap was necessary].

PMID- 12789797
TI  - [The psychosis prodrome in life and poetry of Gunvor Hofmo].

PMID- 12789798
TI  - [Blue anemone--a "medicinal" plant].

PMID- 12789799
TI  - [The Red Cross emblem is not to be abused].

PMID- 12789800
TI  - [Medical equipment and relief work].

PMID- 12789801
TI  - [Thiazides--good first choice preparations in hypertension].

PMID- 12789802
TI  - [Does use of alternative medicine aggravate the survival prognosis in cancer?].

PMID- 12789803
TI  - [Iscador--alternative medicine?].

PMID- 12789804
TI  - [Discouraging about drug therapy].

PMID- 12789805
TI  - [Carotid surgery in the prevention of stroke].

PMID- 12789806
TI  - [Norovirus gastroenteritis at the Ulleval university hospital].

PMID- 12789807
TI  - [When pain goes its own ways. Mechanism-based diagnostics would make the correct
      choice of treatment for patients with chronic pain easier].

PMID- 12789808
TI  - [Sensory sensitization, part I: Mechanisms behind fibromyalgia. "So my wife's
      pain system has become unnecessarily efficient"].
AB  - A pathophysiological mechanism named "nociceptive sensory sensitisation" is
      introduced to explain part of the fibromyalgia pain syndrome as well as several
      local or regional long standing pain conditions like epicondylitis, chronic low
      back pain, whiplash associated disorder, temporomandibular pain disorder and
      trochanteritis. The article is based on a vast rheumatological clinical
      experience on patients presenting with local or wide-spread pain, and on
      literature studies. Sensory sensitisation describes a changed quality in sensory
      nerve pathways with hyperexcitability and facilitated transmission of nerve
      impulses to the sensory cortex. Sensory sensitisation should be considered as a
      pathophysiological reaction originating from tissues and organs exposed to
      "external" overload or trauma, either physical, chemical or biochemical. The
      sensitisation process is usually facilitated by "internal" psychological
      distress.

PMID- 12789809
TI  - [Sensory sensitization, part II: Pathophysiology in dysfunctional disorders.
      Understanding the inner life of the nerve pathways may explain hitherto
      unexplainable symptoms].
AB  - This article is based on a vast clinical experience from patients presenting with
      widespread pain syndromes as well as dysfunctional symptoms from inner organs. A
      literature survey has been performed. Allodynia and hyperalgesia that partly
      explain the fibromyalgia and local myalgia syndromes seem to arise from a
      pathophysiological process of nociceptive sensitisation. It is proposed that the
      concept of "sensory sensitisation dysfunctional disorders" be applied to
      conditions like bronchial hyperreactivity, Da Costas syndrome, Dercum's disease
      (Adipositas dolorosa), dry eyes and mouth syndrome, fibromyalgia, gastralgia,
      globus hystericus, interstitial cystitis, chronic prostatitis, irritable bowel
      syndrome, photo- and phonosensitivity, rhinitis, tension headache, tinnitus,
      vestibulitis syndrome. These dysfunctional disorders cannot be satisfactorily
      explained by presently known pathophysiological models like ongoing inflammatory
      process, tissue degeneration, fibrosis, blood vessel diseases, tumours, immune
      reactions, toxic or deficiency conditions, metabolic disturbances. Neurogenic
      mechanisms also seem to play an important role in the pathophysiology of
      arthritic conditions, and might be worthwhile to include in forthcoming
      discussions concerning the aetiology of chronic inflammatory disease.

PMID- 12789810
TI  - [Adrenogenital syndrome in children and adolescents--new guidelines for
      treatment. An international consensus conference emphasizes the need of team
      work].

PMID- 12789811
TI  - [Strategic learning. A method for an effective self-directed learning].

PMID- 12789812
TI  - [Strategic learning. A good and useful model for physicians' competence
      development].

PMID- 12789813
TI  - [Do we manage to express ourselves explicitly in writing and speaking, with or
      without a computer?].

PMID- 12789814
TI  - [Lars Hertervig and Edvard Munch. Two Norwegian artists balancing between sanity
      and madness].

PMID- 12789815
TI  - [Our responsibility for the epidemics of sick leave].

PMID- 12789816
TI  - [Being woman professor].

PMID- 12789817
TI  - [Persons with the most severe mental disorders must also have the right to care
      and treatment].

PMID- 12789818
TI  - [Basic points of conception of quality assurance in mental health care].
AB  - The article presents conceptual approaches to the problem of quality assurance in
      mental health care, which accumulate a previous national and international
      experience in the field of medical and psychiatric care quality, taking into
      account the results obtained by the authors. The article addresses juridical,
      ethic, economic and organizational aspects of mental health care improvement.
      Attention is drawn to a need in controlling system and quality evaluation based
      on adequate and informative criteria and quality standards and in making
      scientifically founded administrative decisions. Specific criteria for evaluation
      of mental health care quality, taking into account its main components-
      structure, process, results--were suggested.

PMID- 12789819
TI  - [A comparative validation of the scale CES-D, BDI, and HADS(d) in diagnosis of
      depressive disorders in general practice].
AB  - To determine a most precise instrument for diagnostics of depression and a level
      of its severity, a comparative study of 3 questionnaires: Hospital Anxiety and
      Depression Scale (d) (HADS(d)), Beck Depression Inventory (BDI) and Center for
      Epidemiological Studies Depression scale (CED-D) was conducted in 148 patients
      (91 women, 57 men), aged 46.5 +/- 9.34 years. An analysis of sensitivity,
      specificity and predictive values of positive and negative results allowed to
      detect optimal cut off points, distinguishing depressive patients, as follows: =
      18 for CES-D, = 12 for BDI, = 0.89 for HADS(d). For all scales, areas under
      receiver-operator characteristic (ROC) curve (0.97 +/- 0.02, 0.96 +/- 0.02 and
      0.94 +/- 0.02, respectively) proved to be comparable. The optimal cut off points
      for distinct separation between patients with mild and severe depression were
      detected as = 26 for CES-D, = 20 for BDI, = 10 for HADS(d). The area under ROC
      curve for CES-D was higher (0.99 +/- 0.01) than those for BDI (0.86 +/- 0.04) and
      for HADS(d) (0.83 +/- 0.05). The data obtained reveal that the cut off points
      ascertained in the study reduce a chance of depression under diagnosis. All the
      scales could be recommended to interns for primary (screening) diagnostics of
      depression in routine medical care.

PMID- 12789820
TI  - [Pyramidal syndrome in lateral amyotrophic sclerosis: clinico-morphological
      analysis].
AB  - Retrospective clinical analysis with a special focus on pyramidal syndrome
      expression in the disease course as well as morphological study of brain and
      spinal structures in all levels of cortical-spinal projection (from brain motor
      cortex to spinal lumbar segments) have been conducted for 11 section cases of
      lateral amyotrophic sclerosis (LAS), sporadic type. Two groups of patients were
      studied: with pronounced pyramidal syndrome (spasticity, hyperreflexia, etc)--7
      cases and with some signs of pyramidal deficiency (anisoreflexia, stability of
      peritoneal reflexes)--4 cases. Pyramidal syndrome in LAS is considered as an
      emergence of current neurodegenerative process, embracing a significant part of
      upper motor neurons of both precentral convolution and its axons along the whole
      length of cerebrospinal axis in the form of cytoplasmic inclusions and axonal
      spheroids. A presence of pathomorphological changes in other upper segmental
      structures of motor control reveals their role in pyramidal deficiency.
      Comparative analysis showed that expression of pyramidal syndrome signs and its
      correlation to atrophic paresis appearances is specifically determined by the
      severity of upper and lower motor neurons lesions. With regard to morphological
      changes in CNS structures, the peculiarities of some pyramidal syndrome
      appearances in LAS are analyzed.

PMID- 12789821
TI  - [Auto-chronometric abnormalities in patients with various location of cerebral
      pathology].
AB  - Dysfunction of limbic structures of temporal lobes (mainly, hippocampus),
      chiasmus, hypothalamus and epiphysis are followed by inner time-keeping disorder.
      In temporal lobes and skull base lesions, auto-chronometric shifts are of the
      same type, being mostly pronounced and not directly connected with either
      locomotor parameters, or with changes of CNS general functional condition.
      Regardless of CNS dynamic state disorders, any serious defects of endogenous time
      keeping were not found both in patients with spinal or vertebral injuries,
      including those with tumor processes, and in patients with extensive lesions of
      fronto-parietal neocortex regions. These findings allow considering cerebral
      oscillator formations--hippocampus, hypothalamic region, epiphysis--as the
      structures involved directly in physiological mechanisms of autochronometric
      regulation.

PMID- 12789822
TI  - [Psychological mechanisms of communication disorders in schizophrenics and their
      relatives].
AB  - The study aimed at searching for mechanisms of communicative impairments in
      patients with schizophrenia and their relatives. To evaluate a contribution of
      attention and memory to communication efficacy and to ability for understanding
      mental states of others, 100 patients with schizophrenia and schizoaffective
      psychosis, 150 their healthy relatives and 145 controls have been studied. The
      results confirmed a presence of communicative deviations in the patients with
      schizophrenia and their relatives. In these groups, communication deficit was
      determined by disturbance of 1 out of 4 communication principles--the principle
      of information quantity. Attention and memory did not exert any significant
      influence on communication efficacy in the patients and their relatives. Distinct
      deterioration of fulfilling the tasks demanding mentalizing ability was found
      only in the patients. However, no correlation was revealed between this
      deterioration and communication peculiarities.

PMID- 12789823
TI  - [Borderline mental disorders in patients with prostate cancer].
AB  - Sixty five patients, aged 48-87, with prostate cancer at different stages were
      studied. Borderline mental disorders were found in all the patients. In the
      majority of them, affective disorders in the form of anxiety-depressive (52.3%)
      and astheno-depressive (24.6%) syndromes were observed. Astheno-hypochondriacal
      and dysphoric syndromes were detected less frequently (in 15.4% and 7.7% of the
      cases, respectively).

PMID- 12789824
TI  - [Comparative efficacy of betaserc and cinnarizine of vertigo in patients with
      migraine].
AB  - Headache and vertigo often emerge simultaneously. Fifty six (40%) out of 140
      patients complaining of vertigo were studied. Emerging in the aura and/or in
      headache phases, vertigo was more frequently registered in patients suffered from
      migraine with aura (57%). Vertigo associated with migraine was diagnosed in 25%
      of the cases. The patients were randomized into 2 equal identical groups, one of
      which was treated by betaserc (16 mg, 3 times daily before meal) and the other
      one was given cinnarizine (25 mg, 3 times daily). Treatment duration was 12
      weeks. Reduction of vertigo attacks frequency and headache by 50% and over, in
      comparison to the baseline period, was considered as beneficial. Fifty three
      (95%) patients completed the treatment course. Decrease of a risk for negative
      results and a frequency of positive effect of vertigo therapy were significantly
      higher in the group receiving betaserc. Reduction of monthly relapses by 50% and
      over was detected in 79% of the patients of betaserc group and in 52% of those of
      cinnarizine one. Migraine attacks monthly frequency was diminished by 43% and
      64%, respectively. Therefore, betaserc is considered for using as vertigolytic
      medication and for migraine attacks prevention.

PMID- 12789826
TI  - [Brain bioelectrical activities in heroin addicts during early abstinence
      period].
AB  - Standard 19-channel EEG registration was performed in 30 heroin addicts (mean age
      21.7 +/- 2.8 years, daily heroin abusing duration--12.2 +/- 8.0 months, heroin
      dose per day--0.42 +/- 0.29 g, abstinence duration--12.3 +/- 8.1 days).
      Qualitative EEG changes, being observed in more than 70% of the cases, included
      low voltage of background activity with depression of alpha rhythm and increase
      in beta activity; large amount of low amplitude waves in central regions; low
      reactivity to stimulation. The patients with daily heroin doses more than 0.5 g
      demonstrated slowing of alpha rhythm in comparison to those with lower doses (8.9
      +/- 0.8 Hz vs 10.3 +/- 2.0 Hz, p < 0.05). In follow-up study, obvious or even
      complete normalization of the EEG was observed in most of the cases during the
      first months of abstinence.

PMID- 12789825
TI  - [Cipramil treatment of neurotic depression].
AB  - Thirty one patients, aged 23-48 years, with ICD-10 diagnosis of psychogenic
      neurotic depression (F32.0 and F32.1), were studied. According to antidepressants
      used, the patients were divided into 2 groups, of which the test one included 19
      patients treated by cipramil (20-40 mg/day) and the comparative one consisted of
      12 patients treated with amitriptilin (25-50 mg/day). The treatment duration was
      28 days. The patient's state was evaluated, using clinical approach and
      instrumental methods, i.e. Hamilton depression scale, before treatment and on
      14th and 28th days. After cipramil treatment, 14 patients out of 19 exhibited an
      improvement, with 5 revealing neurotic symptoms compensation. However, 5 patients
      proved to be resistant to the medication. In amitriptilin treatment, complete
      depression reduction was found only in 1 patient, with pronounced improvement
      being shown in 8 out of 12 patients. No changes in the patient's state were
      revealed for 3 cases. Cipramil treatment was not accompanied with any side
      effects.

PMID- 12789827
TI  - [Glycosaminoglycans and their fractions in patients with hereditary neuromuscular
      disorders].
AB  - Hereditary neuromuscular disorders (HNMD), with population incidence 1:3000, are
      characterized in most cases by progressive course and treatment resistance and
      patient's disabling. To study the involvement of the tissue-connecting structures
      in the pathogenesis, glycosaminoglycans and their fractions were determined in
      blood serum. The test group involved 40 patients with hereditary myotonia,
      myodystrophy, neuropathy and spinal muscular atrophy and control one consisted of
      27 healthy age- and sex-matched subjects. The study was conducted using anion
      exchange chromatography on DEAE-cellulose. Comparing to controls, significant
      increase of total glycosaminoglycans and decrease of gilauronic acid fraction (p
      < 0.05) were found in HNMD patients, with no differences being detected between
      nosologic entities. Reverse correlation (r = -0.46) was revealed between
      patient's age and glycosaminoglycans concentration in blood serum. We concluded
      on intracellular and intercellular matrix heteropolyglycans metabolism
      dysregulation in the patients and suggested a part of HNMD pathogenesis scheme.

PMID- 12789828
TI  - [Biological and social correlates of favorable and unfavorable neurosis course].
AB  - Four hundred ninety seven patients with neurosis of Astana (Kazakhstan)
      community, 116 men and 381 women, have been studied. The patients were traced in
      5-year follow up study. Favorable and unfavorable types of the disorder were
      established, the latter being characterized by transforming into neurotic
      personality development. The influence of endogenous and environmental factors on
      neurosis prognosis was examined. To elaborate adequate measures for preventing
      neurotic personality development, criteria for favorable and unfavorable
      prognosis of neurotic disorders were suggested.

PMID- 12789829
TI  - [Some psychological features of opioid addicts].

PMID- 12789830
TI  - [Effects of the drug magne B6 on the trace element homeostasis of rat brain].

PMID- 12789832
TI  - [A proposal for continuing medical education].

PMID- 12789831
TI  - [Quality assurance in medical/mental health care].

PMID- 12789833
TI  - [Use of devices for spine immobilization for trauma patients at the emergency
      department: review of the literature].
AB  - Trauma care implies the use of various devices for partial or total spine
      immobilization in order to prevent secondary damages due to medical
      interventions. The aim of this review of the medical and nursing literature of
      the last 10 years is the analysis of the latest evidences produced and the
      comparison with the recommendations provided by the most recent clinical
      guidelines. The following key-words were used ("cervical collar", "spinal board",
      "trauma", "vacuum mattress", "stretcher", "emergency department", "spinal
      trauma") and clinical trials, surveys and descriptive studies were searched in
      Pub-med. According to the most recent studies the spine table should be removed
      within two hours from the arrival to the Emergency Department in favour of a
      stretcher with a padded rigid surface. Safety straps for securing the patient on
      the spinal board should replace spider burlap for trauma patients. Of utmost
      importance is the correct positioning of a cervical collar of the right size, the
      positioning of low pillows under occipitis in order to obtain the neutral
      position of the head and its stabilization through the blocking of the head and
      trunk.

PMID- 12789835
TI  - [Models, methods, clinical contents in the specialized degree in nursing
      sciences].
AB  - The document presented is the result of a consensus conference where nurses
      involved in teaching, direct care and management discussed with professionals and
      experts of other disciplines on the role of the clinical teaching at specialistic
      level. Nursing education in fact recently underwent a re-organization therefore
      after the degree (first level) there is a second level (Specialistic degree and
      PhD) first and second level master courses. The main question of the consensus
      conference was if there is a role and what are the contents of clinical nursing
      to be taught at specialistic level. A consensus was reached on the importance of
      not separating the teaching of the methods from the contents of care, to allow
      the production of new knowledge relevant for patients' care. A nurse with a
      specialistic degree should be able to plan and implement innovative models of
      care based on scientific knowledge; to recognise unexpected and rapidly evolving
      problems; to plan and implement, in collaboration with other professionals,
      complex educational interventions; study and explore principles and theories of
      helping relationship. The differences in contents and methods of clinical
      teaching between master and specialistic degree need to be further discussed and
      explored.

PMID- 12789834
TI  - [Variability of intestinal preparation in patients undergoing stomach, intestine,
      uterus surgery at 4 hospitals].
AB  - The standard preoperative care of the surgical wards of 4 hospitals for patients
      undergoing abdominal (stomach and colon) and gynaecological (uterum) surgery has
      been described. Date collection included the comparative assessment of standard
      protocols and intervention, with nurses in charge of the preoperative care.
      Patients undergoing colon surgery may be prescribed an ash-free diet for 7-10
      days or may eat normal meals till two days before the surgery. The same
      variability exists for the antimicrobial prophylaxis and its route of
      administration. Patients are not allowed to drink from the midnight before the
      surgery. Enemas administered the afternoon before the surgery may contain castor
      oil. A systematic review of preoperative care is warranted and guidelines for an
      evidence based practice should be provided in order to reduce the variability and
      improve the effectiveness of preoperative care.

PMID- 12789836
TI  - [Guide for self-teaching the management of infusion therapy through peripheral
      vascular access].

PMID- 12789837
TI  - [Economic embargos can also be a violation of human rights. The impact of
      sanctions on the health of children].

PMID- 12789838
TI  - Assign cases based on acuity level of patients, not just on the number.

PMID- 12789839
TI  - Time studies facilitate case assignment.

PMID- 12789840
TI  - Electronic system places patients in post-acute care.

PMID- 12789841
TI  - Safety concerns should not end with discharge.

PMID- 12789842
TI  - Baptist Health Care's performance standards.

PMID- 12789843
TI  - Take a deep breath, now prepare for EDI deadline.

PMID- 12789844
TI  - Speed up orders for inpatients held in ED.

PMID- 12789845
TI  - Use protocol to send inpatient holds upstairs.

PMID- 12789846
TI  - Pimecrolimus cream for atopic dermatitis.
AB  - Pimecrolimus (pronounced pi-me-kro-ly-mus) cream (Elidel--Novartis) is a new
      topical immunosuppressant licensed for the treatment of patients aged 2 years or
      over with mild or moderate atopic dermatitis. It is the second topical treatment
      in this class, the first being tacrolimus ointment (Protopic--Fujisawa) which we
      reviewed in October 2002. Pimecrolimus is the first such treatment to be licensed
      for first-line use in atopic dermatitis. It can be used either as short-term
      treatment for actively inflamed lesions, or as intermittent long-term treatment
      to prevent the progression of early symptoms and signs to flares. The company
      claims that "when used at the first sign of redness and itch" pimecrolimus cream
      is "the only treatment clinically proven to prevent progression to flare", and
      that many people using it have "eliminated or reduced steroid use". Here, we
      consider the place of pimecrolimus cream in the management of atopic dermatitis.

PMID- 12789847
TI  - Management of pancreatic cancer.
AB  - Each year in the UK, pancreatic cancer is diagnosed in around 7,000 people. At
      least 80% of these present with locally advanced inoperable or metastatic disease
      and most patients with pancreatic cancer die within a year of diagnosis. Here, we
      review treatment options, dealing exclusively with adenocarcinoma (the commonest
      tumour type), focusing on whether they cure the disease, prolong survival,
      alleviate symptoms or improve quality of life.

PMID- 12789848
TI  - Notes on the World Day of the Sick.

PMID- 12789849
TI  - Mission and mentoring at St. Joseph Health System.

PMID- 12789850
TI  - Make partners of your local clergy.

PMID- 12789851
TI  - Susceptibility testing for children.

PMID- 12789852
TI  - Portraits in collaboration. The new covenant goes into action in Cleveland.
AB  - In 2002 Catholic Charities USA and the Catholic Health Association sponsored a
      study assessing the state of collaboration in Catholic ministries across the
      United States. The study was conducted by Health Systems Research, Inc., and was
      funded in part by a grant from SC Ministry Foundation. As part of the study,
      researchers visited give sites (St. Petersburg/Tampa, FL; Cleveland; Wichita, KS;
      Orange County, CA; and Albany, NY) to learn what makes for successful
      collaboration. This is the second in a series of articles for Health Progress
      highlighting the findings from this study, which will become available later this
      year.

PMID- 12789853
TI  - Living our mission. Healing is mutual for nurses who attend to their patients
      lovingly.

PMID- 12789854
TI  - Spirituality and work. Indianapolis's Seton Cove Center seeks to integrate
      spirituality into the workplace.

PMID- 12789855
TI  - Becoming a health care administrator. A survey reveals a spirit of service to be
      the most important ingredient.

PMID- 12789856
TI  - Transforming the workplace. Ten strategies can help increase employee
      satisfaction.

PMID- 12789857
TI  - Strategic planning for a turnaround. A two-facility Missouri system recaptures
      the leadership position in its local market.

PMID- 12789858
TI  - The technology of partnership. Physicians must play a larger role in decisions
      concerning capital and technology.

PMID- 12789859
TI  - The church and diversity. Catholic social teaching provides a firm basis for
      following the principle of inclusion.

PMID- 12789860
TI  - An engaged spirituality.

PMID- 12789861
TI  - Enrollee satisfaction with three Florida Medicaid managed care programs.
AB  - A study was undertaken to compare adult enrollees' satisfaction with three
      Medicaid Programs operating in South Florida: (1) the provider service network
      (PSN), (2) MediPass, and (3) Medicaid HMOs. The Consumer Assessment of Health
      Plans Study 2.0 Medicaid Adult instrument was used to collect information on four
      global ratings and five composite ratings. MediPass enrollees were satisfied with
      their overall health care, whereas PSN enrollees gave only average scores for
      their doctors, specialists, overall health care, provider communication, and
      staff helpfulness. The HMO enrollees were satisfied with their specialists,
      health plan, access to care, promptness of care, staff helpfulness, and
      member/customer service. Improvements in satisfaction would require different
      interventions in each of the programs.

PMID- 12789862
TI  - Health law or stealth law? The back-door regulation of business associates.

PMID- 12789863
TI  - Rebates and other drug-cost issues.

PMID- 12789864
TI  - The budgetary crunch and how to rationally decide what to cut.

PMID- 12789865
TI  - The effect of increasing clinical autonomy in workers' compensation.
AB  - Many health plans are shifting to less-restrictive managed care options that
      increase provider and consumer autonomy. Although intended to improve
      satisfaction and quality, the effect of these changes on utilization and
      expenditures is not yet known. Evidence from changes increasing clinical autonomy
      in a statewide workers' compensation system may be illustrative for managed
      health care plans as to how these changes may result in costly and unintended
      consequences.

PMID- 12789866
TI  - Inpatient length of stay and atypical antipsychotic use among elderly patients
      with psychiatric disorders and Alzheimer's disease.
AB  - This study evaluated length of stay (LOS) associated with atypical antipsychotic
      monotherapy in inpatients with Alzheimer's disease. In addition to
      sociodemographic information, data were also obtained on severity of illness,
      medications, used, patient satisfaction, and hospitalization. Sociodemographics
      and severity of illness at admission were similar in groups taking olanzapine (N
      = 66), quetiapine (N = 41), and risperidone (N = 147). The mean LOS for
      risperidone was significantly shorter than that for quetiapine (12.3 vs. 16.4
      days, respectively; P < .02), but the difference between risperidone and
      olanzapine did not reach statistical significance (12.3 vs. 14.9 days,
      respectively; P < .08). The savings associated with risperidone versus quetiapine
      therapy, based on an estimated daily hospital care cost of $492, was $2,017.20
      per patient.

PMID- 12789867
TI  - Pharmacists, public air concerns about risk management programs.

PMID- 12789868
TI  - Cancer vaccines offer new treatment modality.

PMID- 12789869
TI  - Nursing and pharmacy agree: it is time for change.

PMID- 12789870
TI  - Niacin for dyslipidemia: considerations in product selection.
AB  - The efficacy and safety profiles of various forms of niacin for treating
      dyslipidemia are described. Niacin is well recognized for treating dyslipidemia
      in adults and has been shown to be effective in reducing coronary events. It has
      a broad range of effects on serum lipids and lipoproteins, including lowering
      total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides.
      Niacin is the most effective lipid-modifying drug for raising high-density
      lipoprotein (HDL) cholesterol levels and has been shown to lower Lp(a)
      lipoprotein. Niacin reduces triglycerides and very-low-density-lipoprotein and
      LDL cholesterol synthesis, primarily by decreasing fatty acid mobilization from
      adipose tissue. Niacin appears to raise HDL cholesterol by reducing hepatic
      apolipoprotein A-l clearance and enhancing reverse cholesterol transport. Niacin
      is metabolized through a conjugation or nicotinamide pathway. Standard immediate
      release niacin is metabolized primarily through the conjugation pathway, which
      results in a high frequency of flushing. Long-acting niacin is metabolized
      through the nicotinamide pathway, which results in less flushing but increases
      the risk of hepatotoxicity. Extended-release niacin has a more balanced
      metabolism and causes fewer of both types of adverse effects. Improved serum
      lipid levels during niacin therapy have been associated with clinical and
      angiographic evidence of reduced coronary artery disease, especially when
      combined with statins. Niacin is particularly useful for managing high
      triglyceride and low HDL cholesterol levels as well as the lipid abnormalities
      associated with metabolic syndrome, including those commonly encountered in
      patients with diabetes. Several niacin products are available with significant
      differences in their safety and efficacy profiles. Health care providers must
      consider the differences between agents when recommending niacin for dyslipidemia
      treatment.

PMID- 12789871
TI  - Permeation of cytotoxic formulations through swatches from selected medical
      gloves.
AB  - The permeability of selected medical glove materials to various cytotoxic agents
      is described. Fifteen cytotoxic agents were prepared at the highest
      concentrations normally encountered by hospital personnel. Four single-layer and
      two double-layer glove systems made of two materials--latex and neoprene--were
      exposed to the drugs for 30, 60, 90, 120, 150, and 180 minutes. Circular sections
      of the glove material were cut from the cuff and evaluated without any
      pretreatment. Permeability tests were conducted in an apparatus consisting of a
      donor chamber containing the cytotoxic solution and a collection chamber filled
      with water (the acceptor medium). The two sections were separated by the glove
      material. Permeating portions, collected in water as the acceptor medium, were
      analyzed by either ultraviolet-visible light spectrophotometry or high
      performance liquid chromatography (HPLC). Permeation rates were calculated on the
      basis of the concentration of the cytotoxic agent in the acceptor medium.
      Spectrophotometric measurements were taken every 30 minutes, and HPLC analysis
      was performed at the end of the three-hour period. Average permeation rates for
      14 drugs were low (< 0.2 nmol/[min.cm2]) or no permeation was detected in all
      glove materials. All glove materials tested were impermeable to most of the
      cytotoxic agents over a period of three hours. Carmustine was the only agent that
      substantially permeated single-layer latex glove materials. Permeation of most
      tested cytotoxic formulations was low through swatches of material from various
      medical gloves.

PMID- 12789873
TI  - Stability of nifedipine in an extemporaneously compounded oral solution.
AB  - The stability of nifedipine in an extemporaneously compounded oral solution is
      described. A solution of nifedipine 10 mg/mL was prepared from commercially
      available nifedipine powder with polyethylene glycol 400, glycerin, and
      peppermint oil. Four samples were stored in amber glass bottles at room
      temperature under fluorescent lighting and analyzed in duplicate. Samples were
      analyzed immediately and at 7, 14, 23, and 35 days. Eight samples were stored in
      amber oral syringes and eight in amber oral syringes wrapped in aluminum foil;
      all were stored at room temperature under fluorescent lighting. Samples from foil
      wrapped syringes were analyzed at 7 and 14 days; samples not wrapped in foil were
      analyzed after 7 days. Nifedipine concentrations were measured with a modified
      stability-indicating high-performance liquid chromatographic method. Excessive
      degradation was defined as a greater than 10% loss of initial drug concentration.
      There were no detectable changes in color or odor and no visible solids or
      microbial growth was observed in any sample. Samples in amber glass bottles and
      amber oral syringes wrapped in aluminum foil retained more than 90% of the
      initial nifedipine for 35 and 14 days, respectively. Samples packaged in amber
      oral syringes not wrapped in foil lost over 20% of the initial nifedipine
      concentration within 7 days. Nifedipine 10 mg/mL was stable in an oral solution
      prepared from commercially available powder in a peppermint-flavored vehicle for
      at least 35 days when stored at 22-25 degrees C in amber glass bottles and for at
      least 14 days when stored in amber oral syringes wrapped in aluminum foil.

PMID- 12789872
TI  - Pharmacist involvement in a multidisciplinary inpatient medication education
      program.
AB  - The development of a multidisciplinary inpatient medication education program is
      described. A multidisciplinary group designed and implemented a medication
      education program with defined roles for both nurses and pharmacists. Nurses
      provided medication education to patients during each medication administration
      using specially designed assessment and teaching tools. The nursing staff
      submitted requests for pharmacist consultations for patients with complex
      medication regimens, who were admitted because of a drug-related problem or who
      required additional teaching as determined through the medication education
      assessment form. A complex medication regimen was defined as the administration
      of oral medication more than five different times per day, the start of at least
      5 new medications that would be continued at discharge, or the prescribing of at
      least 10 medications to be taken daily that would be continued at discharge.
      Pharmacists provided education for 19% of admitted patients during a six-month
      period. As a result of pharmacists' interactions with prescribers and nurses, the
      number of medications was reduced in 12% of these patients, and the number of
      medication administrations each day was reduced in 19% of patients. In addition,
      for 33% of patients, pharmacists contacted the prescriber to make recommendations
      beyond the scope of the medication education program that optimized and
      simplified the patient's drug regimen. The development of a structured medication
      education program allowed patients to receive medication education throughout
      their hospitalization from both nurses and pharmacists. Pharmacists provided
      education for patients at highest risk for noncompliance or poor outcomes. Full
      implementation of a medication education program involving staff pharmacists is
      planned.

PMID- 12789874
TI  - Patient outcomes after therapeutic interchange of dolasetron for granisetron.
AB  - The impact of using therapeutic interchange (TI) of dolasetron for granisetron
      for the prevention of chemotherapy-induced nausea and vomiting (CINV) was
      evaluated. An outcomes evaluation was conducted in two cohorts of adult
      outpatients who had not previously received chemotherapy. Before the interchange,
      20 patients were enrolled in a granisetron cohort, and after the interchange to
      dolasetron, 42 patients were matched to the initial cohort. Evaluations using the
      modified Functional Life Index--Emesis (MFLIE) compared changes in functional
      status before and after treatment. Nausea and vomiting frequency, satisfaction
      with antiemetics, reported adverse effects, changes in antiemetic therapy, and
      the use of antiemetics postchemotherapy were also evaluated. Success, defined as
      no vomiting and less than a 2.5-unit change in MFLIE score, was demonstrated in
      45% of granisetron patients and 40% of dolasetron patients (p = 0.461). While
      functional status declined in both groups in response to chemotherapy, the
      changes in MFLIE scores did not differ between agents (-16.8 +/- 20.16 versus 
      19.39 +/- 26.36 in granisetron and dolasetron patients, respectively) (p =
      0.650). Patients were equally satisfied with their prescribed antiemetic therapy,
      although less than half of patients achieved antiemetic success in the 72-hour
      study period. Self-reported adverse events attributed to serotonin type 3
      receptor antagonist use were minimal and not significantly different between
      groups. The TI did not negatively affect patient outcomes and produced savings of
      $143,534 in the first year of the program. TI of dolasetron for granisetron for
      CINV did not affect functional status, nausea control, or patient satisfaction
      with antiemetic therapy.

PMID- 12789875
TI  - Clinical and economic outcomes of a fall-focused pharmaceutical intervention
      program.
AB  - The effects of a fall-focused pharmaceutical intervention program (FFPIP) on the
      clinical and economic outcomes of elderly patients who fall while residing in a
      rehabilitation center are described. The objectives of this retrospective
      observational study were to identify the differences in the number of patient
      falls among elderly patients before and after pharmaceutical interventions,
      identify the cost savings related to decreasing the number of falls, and
      determine whether a relationship exists between falls among the elderly and
      specific medication classes. A data collection tool was developed by the
      investigators to record demographics and medication use. Two hundred patients
      were randomly selected from the preintervention (October 1, 1999-September 30,
      2000) and postintervention (October 1, 2000-September 30, 2001) periods. Two data
      collectors collected data from patient medical records to test the data
      collection tool and ensure accuracy. The number of patient falls was reduced in
      the postintervention group by 47%, resulting in a future savings of $7.74 per
      patient per day. The use of several classes of medication also decreased in the
      postintervention period: cardiovascular agents, 10.7%; analgesics, 6.3%;
      psychoactive drugs, 18.2%; and sedatives and hypnotics, 13.9%. Patients most
      likely to fall were male, greater than 76 years of age, had a cardiovascular- or
      orthopedic-related diagnosis, and were taking analgesics, cardiovascular agents,
      and central nervous system agents, yet the intervention had a more significant
      effect on female patients. Implementation of an FFPIP decreased falls by 47% and
      decreased the use of cardiovascular drugs, analgesics, psychoactive medications,
      and sedatives and hypnotics.

PMID- 12789876
TI  - A pharmacist-managed anticoagulation clinic: six-year assessment of patient
      outcomes.

PMID- 12789877
TI  - Evaluation of a teaching certificate program for pharmacy residents.

PMID- 12789878
TI  - Compatibility of calcium and phosphate in four parenteral nutrition solutions for
      preterm neonates.

PMID- 12789879
TI  - Restriction of vancomycin use at a university hospital in Thailand.

PMID- 12789880
TI  - Pharmacy students' knowledge of medication-error reporting.

PMID- 12789881
TI  - Formulary management strategies for type 3 serotonin receptor antagonists.
AB  - The efficacy of type 3 serotonin (5-hydroxytryptamin) (5-HT3) receptor
      antagonists in preventing nausea and vomiting associated with cancer
      chemotherapy, radiation therapy, and surgery and the role of practice guidelines
      for the use of these agents in controlling antiemetic drug costs without
      compromising patient care are described. Nausea and vomiting caused by cancer
      chemotherapy, radiation therapy, and surgery can have a negative impact on
      quality of life and patient outcomes. The 5-HT3 receptor antagonists are
      effective for preventing nausea and vomiting from these causes. Oral 5-HT3
      receptor antagonist therapy is as effective as intravenous therapy, while usually
      costing less. Various factors associated wtih the patient and the chemotherapy,
      radiation therapy, or surgery that increase the risk for nausea and vomiting have
      been identified. Practice guidelines have been developed in which 5-HT3 receptor
      antagonist therapy is reserved for patients at high risk for nausea and vomiting
      based on these various factors. The use of such practice guidelines at Memorial
      Sloan-Kettering Cancer Center limited antiemetic drug expenditures despite an
      increase in the number of patients receiving cancer treatment without
      compromising emetic control or quality of life. The use of special order forms
      improved compliance with the practice guidelines.

PMID- 12789882
TI  - Formulary decision-making about cephalosporins with similar therapeutic uses.
AB  - The various costs and intangible factors that enter into formulary decisions in
      an era of increasingly frequent drug product shortages that can adversely affect
      patient care and increase treatment costs are described. Pharmacy administration
      at Carolinas HealthCare System analyzed the costs associated with making a
      formulary switch from the third-generation cephalosporin ceftriaxone to
      cefotaxime, which recently became available in generic form and has a similar
      spectrum of antimicrobial activity and therapeutic uses. Hard dollar costs for
      purchasing drugs and the supplies needed to administer them; soft dollar costs
      for staff time spent acquiring, preparing, and administering doses; and
      intangible factors were considered. A reliable supply of drug product from the
      manufacturer was an important intangible factor because of frequent drug
      shortages in the past few years and the adverse effect on patient care and the
      increased soft dollar costs associated with these shortages. Administrators at
      Carolinas HealthCare System decided not to make the proposed formulary change
      after weighing the many factors and costs.

PMID- 12789883
TI  - Antimicrobial formularies: can they minimize antimicrobial resistance?
AB  - The relationship between antimicrobial drug use and resistance rates and the
      implications for antimicrobial formularies are described. Efforts to restrict
      antimicrobial drug use to reduce resistance in certain microorganisms have been
      accompanied by increases in resistance in other microorganisms. Random cycling of
      a variety of antimicrobial agents to treat infections caused by the same
      microorganism in different patients within a health care institution has been
      advocated as a means to reduce antimicrobial resistance. Analysis of actual
      antimicrobial drug use and resistance data from a network of 40 hospitals
      revealed wide variability in antimicrobial use. The specific type and volume of
      antimicrobial agents used appear to play key roles in determining resistance
      rates. It may be feasible to optimize diversity in antimicrobial drug use and
      minimize resistance by making judicious changes to the antimicrobial formulary.

PMID- 12789884
TI  - Information technology. The $5 billion plan.

PMID- 12789885
TI  - Finance. Revenue cyclers.

PMID- 12789886
TI  - Biotech. Practical genomics.

PMID- 12789887
TI  - Customer service. Hold on there.

PMID- 12789888
TI  - Quality of care. The house call is back.

PMID- 12789889
TI  - The data page. Top department margins.

PMID- 12789890
TI  - Air quality. Scents-ative.

PMID- 12789891
TI  - Your move.
AB  - Welcome to the age of transparency. Spurred by an unprecedented convergence of
      forces, dissemination of hospital performance data is at the forefront of the
      quality movement. Thanks to an initiative led by the AHA and other groups,
      hospitals have the opportunity to define quality and decide how it will be
      measured and reported. Will they?

PMID- 12789892
TI  - Surviving medical malpractice madness.
AB  - Mind-bending increases in medical malpractice insurance rates are driving
      physicians out of certain regions or out of medicine altogether, forcing
      hospitals to make tough choices such as eliminating services or cutting staff.
      Hospitals desperate to keep physicians are trying a number of strategies, from
      banding together to start their own insurance companies to reducing the amount of
      insurance they require their doctors to carry.

PMID- 12789893
TI  - Bar code bandwagon.
AB  - The Food and Drug Administration issued a proposed rule in March requiring bar
      codes on all medications. Most expect that the technology will be commonplace in
      hospitals before the FDA's three-year window. A handful of systems are leading
      the way.

PMID- 12789894
TI  - Six sigma in action. Case studies in quality put theory into practice.
AB  - Case studies of four hospitals show how Six Sigma can be used for everything from
      reducing ED hold time to cutting down on medical errors. Our examples pinpoint
      the costs of implementation and the savings and other benefits derived.

PMID- 12789895
TI  - Working well.
AB  - In health care as in other fields, this is the age of specialization. Yet while
      expertise in a precise field may be good for the advancement of knowledge, it can
      hinder collaboration.

PMID- 12789896
TI  - A short history of randomized experiments in criminology. A meager feast.
AB  - This article discusses advantages of randomized experiments and key issues raised
      in the following articles. The main concern is the growth and decrease in the use
      of randomized experiments by the California Youth Authority, the U.S. National
      Institute of Justice, and the British Home Office, although other experiments are
      also discussed. It is concluded that feast and famine periods are influenced by
      key individuals. It is recommended that policy makers, practitioners, funders,
      the mass media, and the general public need better education in research quality
      so that they can tell the difference between good and poor evaluation studies.
      They might then demand better evaluations using randomized experiments.

PMID- 12789897
TI  - The "experimenting agency". The California Youth Authority Research Division.
AB  - During the 1960s and 1970s, the California Youth Authority embarked on a series
      of randomized field trials to test interventions for juvenile and young adult
      offenders. This article examines the institutional and political reasons why
      rigorous tests were adopted for such interventions as the Community Treatment
      Program. It also describes the effect these trials had on the agency and on
      California justice, as well as how the experimental method eventually became less
      often used in the Youth Authority. The authors explore some general reasons why
      this happened.

PMID- 12789898
TI  - The Home Office and random allocation experiments.
AB  - By examining the history of the random experiment in the Home Office in the
      United Kingdom, this article demonstrates that research is not an altogether
      rational process and that fashion, personality, and politics are at least as
      important as science and evidence when setting research and policy programs and
      determining methodologies. The article also shows that even in 1970, the research
      world was a village and that issues and fashions on one side of it could
      determine the outcome of decisions on the other side, even though they had no
      direct relevance. On a more optimistic note, the article shows how the fashions
      go in cycles so that if you could not get the research funded in the last cycle,
      just wait 20 years for the cycle to come around and try again.

PMID- 12789899
TI  - Explaining feast or famine in randomized field trials. Medical science and
      criminology compared.
AB  - A feast of randomized controlled trials (RCTs) in medical science and comparative
      famine in criminology can be explained in terms of cultural and structural
      factors. Of central importance is the context in which the evaluation of
      interventions is done and the difference in status of situational research in the
      two disciplines. Evaluation of medical interventions has traditionally been led
      by practitioner (clinical) academics. This is not the case in criminal justice,
      where theory has had higher status than intervention research. Medical science
      has advanced in, or closely associated with, university teaching hospitals, but
      links between criminology and criminal justice services are far more tenuous. The
      late development of situational crime prevention seems extraordinary from a
      medical perspective, as does the absence of university police schools in the
      United Kingdom and elsewhere. These structural and cultural factors explain
      concentration of expectation, resource, and RCT productivity in medical science.
      The Campbell Collaboration and the Academy of Experimental Criminology are forces
      which are reducing this polarization of feast and famine in RCTs. But unless
      scientific criminology is embedded in university schools which are responsible
      for the education and training of law, probation, and police practitioners,
      convergence in terms of RCTs and implementation of findings in practice seems
      unlikely.

PMID- 12789900
TI  - The production of criminological experiments.
AB  - This article examines the production of crime and justice field experiments
      during the 1990s. Data were collected on the characteristics of criminological
      experiments funded by the National Institute of Justice (NIJ), the principal
      research agency of the U.S. Department of Justice, during the 10-year period from
      1991 through 2000. The analyses find that, whereas the funds available for
      research and evaluation at the NIJ increased during this period, the number of
      projects and the amount of funds awarded supporting field experiments declined.
      The article describes the characteristics of the experiments funded and assesses
      the extent to which the reduced support can be attributed to the characteristics
      of NIJ research funding, research topics, researchers, or criminal justice
      operational agencies.

PMID- 12789901
TI  - Ethical practice and evaluation of interventions in crime and justice. The moral
      imperative for randomized trials.
AB  - In considering the ethical dilemmas associated with randomized experiments,
      scholars ordinarily focus on the ways in which randomization of treatments or
      interventions violates accepted norms of conduct of social science research more
      generally or evaluation of crime and justice questions more specifically. The
      weight of ethical judgment is thus put on experimental research to justify
      meeting ethical standards. In this article, it is argued that just the opposite
      should be true, and that in fact there is a moral imperative for the conduct of
      randomized experiments in crime and justice. That imperative develops from our
      professional obligation to provide valid answers to questions about the
      effectiveness of treatments, practices, and programs. It is supported by a
      statistical argument that makes randomized experiments the preferred method for
      ruling out alternative causes of the outcomes observed. Common objections to
      experimentation are reviewed and found overall to relate more to the failure to
      institutionalize experimentation than to any inherent limitations in the
      experimental method and its application in crime and justice settings. It is
      argued that the failure of crime and justice practitioners, funders, and
      evaluators to develop a comprehensive infrastructure for experimental evaluation
      represents a serious violation of professional standards.

PMID- 12789903
TI  - Facility profile. Prairie clinic has holistic appeal.

PMID- 12789905
TI  - Open for business. Strategies for designing retail spaces in health care
      facilities.

PMID- 12789904
TI  - Risky business. Organizations tackle infection control during construction.

PMID- 12789902
TI  - Infection control recommendations for patients with cystic fibrosis:
      microbiology, important pathogens, and infection control practices to prevent
      patient-to-patient transmission.

PMID- 12789906
TI  - Looking ahead. Advice on developing a technology master plan.

PMID- 12789907
TI  - Department benchmarks.

PMID- 12789909
TI  - Keratinized squamous cells in fine needle aspiration of the brain. Cytopathologic
      correlates and differential diagnosis.
AB  - OBJECTIVE: To analyze the differential diagnosis when keratinized squamous cells
      are found in a brain aspirate. STUDY DESIGN: Twenty cases of brain aspirates with
      keratinized squamous cells were retrieved (1982-2001). Diagnoses included
      craniopharyngioma (CP) (n = 11), metastatic squamous cell carcinoma (SCC) (n =
      5), epidermoid cyst (EC) (n = 3) and Rathke cleft cyst (RCC) (n = 1). Aspirates
      were obtained under stereotactic radiologic (CT) guidance. Smears were stained
      with Diff-Quik or Papanicolaou stain, and cell block sections were stained with
      hematoxylin and eosin. Radiologic and histopathologic correlation with subsequent
      resection specimens was performed in selected cases. RESULTS: CP showed cellular
      smears with numerous keratinized squamous cells in a background of degenerated
      cellular and keratinaceous debris. Also noted were clusters of anucleate squamous
      cells, multinucleated giant cells, histiocytes, calcified debris and
      characteristic fragments of basaloid epithelial cells. Metastatic SCC showed
      single cells and tissue fragments of markedly atypical and focally keratinized
      cells with enlarged, hyperchromatic nuclei; prominent pleomorphism in a
      background of necrotic cellular debris and acute inflammatory exudate. EC showed
      numerous isolated keratinized squamous cells often with prominent keratohyaline
      granules and occasional parakeratotic cells in a relatively clean background. RCC
      showed single cells and aggregates of benign-appearing squamous cells admixed
      with numerous anucleate squames and hemosiderin-laden macrophages. Glandular-type
      epithelium was present only rarely. CONCLUSION: Squamous cell-containing lesions
      in the brain present a spectrum of pathologic entities. Although they all display
      the common morphologic denominator of keratinizing squamous cells, subtle
      cytomorphologic differences exist in these lesions, permitting an accurate
      cytopathologic diagnosis. Clinicardiologic features and anatomic location of the
      tumor in the brain are additionally helpful.

PMID- 12789908
TI  - The right prescription. Managing pharmaceutical waste is environmentally correct
      and the law.

PMID- 12789911
TI  - Hydatid cyst in soft tissues mimicking malignant tumors. Diagnosis by fine needle
      aspiration cytology.
AB  - OBJECTIVE: To evaluate the role of fine needle aspiration cytology in the
      diagnosis of soft tissue hydatid cysts. STUDY DESIGN: Five cases of soft tissue
      hydatid cyst were diagnosed primarily by fine needle aspiration cytology.
      RESULTS: In all cases, large fragments of acellular material, finely lamellated,
      were found. There were no complications related to fine needle aspiration, and
      histologic studies confirmed the diagnosis of hydatid cyst. CONCLUSION: When
      acellular, laminated fragments suggestive of a laminated layer are identified on
      smears, hydatid cyst should be considered in the differential diagnosis, even in
      atypical locations and in the absence of hooklets, protoscolices or both.

PMID- 12789910
TI  - Fine needle aspiration biopsy for improving the diagnostic accuracy of cut needle
      biopsy of focal liver lesions.
AB  - OBJECTIVE: To determine the value of fine needle aspiration biopsy (FNAB) in
      comparison to cut needle biopsy (CNB) for the diagnosis of malignancy of focal
      liver lesions. STUDY DESIGN: A retrospective analysis was conducted on 68 FNAB
      and 49 CNB procedures performed on 62 patients with focal liver lesions. RESULTS:
      Cytology permitted a diagnosis of the lesion in 78% of cases. When punctures with
      insufficient material were excluded (11), the diagnostic accuracy of FNAB was
      93%. For the 49 patients who underwent both procedures, FNAB and CNB had the same
      diagnostic accuracy, 78%, when considered separately and of 88% when considered
      in combination. Sensitivity, specificity and positive predictive value were
      similar for the 2 techniques. The negative predictive value was 64% for FNAB and
      CNB used separately and reached 78% when the 2 techniques were combined. There
      were no complications during the execution of FNAB and CNB. CONCLUSION: FNAB is
      an effective and safe method for the diagnosis of focal hepatic lesions, with
      diagnostic accuracy similar to that of CNB. When the 2 techniques are combined,
      the accuracy of the diagnosis of malignancy of focal liver lesions increases.

PMID- 12789912
TI  - Endoscopic ultrasound-guided fine needle aspiration of the pancreas. Diagnostic
      utility and accuracy.
AB  - OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB)
      is regarded as a safe and reliable procedure for diagnosing and staging of
      pancreatic neoplasms. This study retrospectively evaluated both the diagnostic
      utility and accuracy of pancreatic EUS-FNABs and potential cytologic pitfalls
      when using Diff-Quik stain for on-site evaluation. STUDY DESIGN: Pancreatic EUS
      FNABs performed between 1995 and 1998 were identified from the files of the
      Department of Pathology. All patients were studied via a linear-array ultrasound
      endoscope with an FNAB device. Immediate evaluation of the specimen by a
      pathologist using air-dried slides and Diff-Quik stain was done on all cases. An
      average of five passes (range, three to nine) were performed. Five cytologic
      categories were identified: nondiagnostic, benign, atypical, suspicious and
      malignant. EUS disease staging, histologic correlation and clinical follow-up
      were reviewed. RESULTS: Sixty-nine consecutive pancreative FNABs were evaluated
      in the study period. The patients comprised 38 females and 31 males with a mean
      age of 65 years (range, 36-83). Histologic correlation was available on 40
      patients, and follow-up was available on the remaining 29. The cytologic
      diagnoses included: 31 malignant, 8 suspicious, 6 atypical, 20 benign and 4
      nondiagnostic. Forty-three cases were true positive, 9 were true negative, 2 were
      false positive, and 11 were false negative. The overall sensitivity was 80% and
      specificity was 82%. CONCLUSION: The study showed that cytologic evaluation of
      pancreatic EUS-FNABs has 80% sensitivity and 82% specificity. False negative
      diagnosis was usually due to sampling error. A nondiagnostic cytologic diagnosis
      should be rendered in the absence of adequate sampling of a lesion. On-site
      cytologic evaluation of EUS-FNABs aids in guaranteeing specimen adequacy, and the
      pathologist should be trained to evaluate Diff-Quik-stained samples.

PMID- 12789913
TI  - Fine needle capillary sampling of eyelid masses. A study of 70 cases.
AB  - OBJECTIVE: To study the cytomorphology of eyelid tumors, correlate it with
      histopathology and determine the diagnostic accuracy of fine needle capillary
      (FNC) sampling (nonaspiration) in the evaluation of lid tumors. STUDY DESIGN: A
      prospective study of 70 cases of eyelid masses carried out using FNC, with
      confirmation by histology in 66 cases and peripheral blood smear and bone marrow
      examination in 3. Histology was not done in 1 case, and 11 cases were inadequate
      on cytology. The diagnostic accuracy of cytology was 94.73%, and false negativity
      was 5.17%. RESULTS: The ages of the patients ranged from 3 to 75 years, with a
      mean of 40.4. The male/female ratio was nearly equal (37:33). The upper eyelid
      was affected in 45 cases and lower lid in 25 cases. The right eye was affected in
      35 cases, left eye in 34 cases and both eyes in 1 case. Fifteen benign, 35
      malignant and 9 infectious/inflammatory lesions were encountered, with 11
      inadequate smears. CONCLUSION: FNC sampling is an effective method of sampling
      eyelid tumors because it causes little discomfort to the patient and allows the
      operator to maintain better control over the procedure. A distinction between
      inflammatory, benign and malignant lesions and between the types of malignant
      tumors can be made.

PMID- 12789914
TI  - Fibromatosis colli in infants. A cytologic study of eight cases.
AB  - OBJECTIVE: To review eight cases of fibromatosis colli and assess their
      cytomorphologic features. STUDY DESIGN: Cytologic smears from eight patients
      diagnosed as having fibromatosis colli on fine needle aspiration cytology were
      reviewed. RESULTS: Cytologic features of fibromatosis colli are bland-appearing
      fibroblasts and degenerative atrophic skeletal muscle in a clean background.
      Besides these, we found a large number of muscle giant cells; numerous bland,
      bare nuclei; and parallel clusters of fibroblasts. Collagen was seen in all
      cases. CONCLUSION: A confirmatory, noninvasive diagnosis of fibromatosis colli
      can be made by fine needle aspiration cytology alone; invasive diagnostic and
      therapeutic measures are best avoided. Excision biopsy may not be necessary and
      should be reserved for cases with a strong clinicopathologic suspicion of
      malignancy.

PMID- 12789915
TI  - E-cadherin expression on fine needle aspiration biopsies of breast invasive
      ductal carcinomas and its relationship to clinicopathologic factors.
AB  - OBJECTIVE: To evaluate E-cadherin expression on fine needle aspiration biopsies
      (FNAB) of breast ductal invasive carcinomas and to correlate that expression with
      the grade of the tumors, axillary lymph node status, primary tumor size,
      menopausal status, estrogen-progesterone receptors and Bcl-2 expression. STUDY
      DESIGN: One hundred female patients ranging in age from 25 to 82 underwent FNAB
      under ultrasound guidance and were diagnosed as having breast carcinomas. Biopsy
      was done with 22-gauge Chiba needles under local anesthesia. All FNAB specimens
      were stained using Papanicolaou and Giemsa stain, diagnosed cytologically as
      ductal invasive breast carcinomas and confirmed histologically postoperatively. E
      cadherin (L-CAM), monoclonal mouse IgG1, primary antibodies ER (clone 1D5), PGR
      (clone PGR) and Bcl-2 monoclonal antibody (clone 124) were used. Immunostaining
      was performed using the alkaline phosphatase method. RESULTS: The expression
      (transmembrane) of E-cadherin was found in 66 (66%) cases. Decreased expression
      of E-cadherin statistically correlated (P < .005) (chi 2 test) with high grade
      (grade 3) tumors (26.6%), axillary lymph node metastasis (42.2%) (according to
      the TNM classification), premenopausal status (43.1%), negative estrogen
      progesterone receptors (49.1% and 41%, respectively) and negative Bcl-2
      expression (32.2%). No relationship was found between E-cadherin expression and
      primary tumor size. CONCLUSION: E-cadherin evaluation on FNAB specimens can be
      helpful in preoperatively predicting tumor cell differentiation and invasiveness,
      defining a population of patients with breast ductal carcinomas and a possible
      poor outcome, and should be taken into consideration in management of the
      disease.

PMID- 12789916
TI  - Fine needle aspiration cytology of leprous neuritis.
AB  - OBJECTIVE: To document the cytomorphologic features of leprous neuritis and their
      correlation with bacterial density. STUDY DESIGN: A partly retrospective, partly
      prospective study of the fine needle aspiration cytology of enlarged nerves in
      leprosy. Cytomorphologic features of nerve aspirates from 28 patients were
      studied. May-Grunwald-Geimsa and Ziehl-Neelsen staining methods were employed.
      RESULTS: Five cytomorphologic patterns were observed in smears of nerve aspirates
      in 19 group I patients with concurrent skin and nerve lesions: (1) inflammation
      composed of epithelioid cell granulomas (5), bacillary index (BI) = 0; (2)
      epithelioid cell granulomas with necrosis (5), BI = 0-1+; (3) acellular necrosis
      (5), BI = 0-4+; (4) macrophage granuloma (3), BI = 5-6+; and (5) granulation
      tissue (1), BI = 1+. In 9 group II patients with pure neuritic leprosy, 3
      patterns were seen: (1) epithelioid cell granulomas (5), BI 0-6+; (2) epithelioid
      granulomas with necrosis (1), BI = 0; and (3) acellular necrosis (3), BI = 0-6+.
      CONCLUSION: The entire spectrum of leprosy is seen in nerve aspirates. Necrosis
      is often a prominent feature. Recognition of the range of cytomorphologic
      patterns and their correlation with BI contribute to accurate calibration of the
      disease in nerves, resulting in appropriate choice of treatment.

PMID- 12789918
TI  - Extracellular hyaline material in association with other cytologic features in
      aspirates from collagenous spherulosis and adenoid cystic carcinoma of the
      breast.
AB  - OBJECTIVE: To reevaluate breast aspirates showing extracellular hyaline material
      (EHM) and globules to assess if clinicoradiologic and cytologic features could
      help in differentiating between benign and malignant lesions, especially
      collagenous spherulosis (CS) and adenoid cystic carcinoma (ACC). STUDY DESIGN:
      Fine needle aspiration was performed on 884 patients with breast lumps. The
      cytomorphologic features of 6 cases showing EHM, including classic hyaline
      globules (HGs), were analyzed in detail. Three cases also had hemorrhagic nipple
      discharge. Tissue diagnosis (4) and mammography (6) were available. RESULTS:
      Aspirate smears revealed high cellularity composed of monolayers: clusters of
      uniform, small cells; EHM; and HGs surrounded by similar cells. Benign naked
      nuclei and stromal fragments (4), nuclear pleomorphism (3), apocrine cells (2),
      foam cells (2), naked HGs (2) and spindle cells in proximity to HGs were also
      seen (4). Nipple discharge smears showed foam cells, erythrocytes (3) and
      epithelial cell clusters with hyaline material (1). The cytologic diagnosis was
      CS (4) and ACC (2). Histopathology confirmed the diagnosis of CS (2) and ACC (1).
      CONCLUSION: There may be a morphologic overlap between the cytomorphologic
      features of CS and ACC, leading to diagnostic errors. The presence of EHM and HGs
      in association with bland cellular features should be interpreted with caution to
      avoid erroneous diagnoses. Histopathology is mandatory in these cases because of
      their different prognostic implications.

PMID- 12789917
TI  - Mammary pseudoangiomatous stromal hyperplasia. A reappraisal of the fine needle
      aspiration cytology findings.
AB  - OBJECTIVE: To describe and reevaluate the fine needle aspiration cytology
      findings of pseudoangiomatous stromal hyperplasia (PASH) of the breast, with
      histologic, immunohistochemical and ultrastructural correlation. STUDY DESIGN:
      The authors reviewed the clinical features, fine needle aspiration cytology,
      histology and immunohistochemical results in all cases of mammary PASH
      encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4
      year period from January 1998 to May 2002. Ultrastructural examination was
      carried out in a selected example. The findings were compared with those in the
      literature. RESULTS: Four cases of PASH of the breast were encountered during the
      study period. The ages of the patients ranged from 34 to 56 years. One of them
      was a male presenting with gynecomastia. Only 2 cases had fine needle aspiration
      biopsies with a satisfactory cellular yield available for review. The cytospin
      preparations were of moderate cellularity and showed cohesive clusters of bland
      looking ductal cells in a background of single, naked nuclei and some spindle
      cells containing fine chromatin and a discernible amount of cytoplasm. Occasional
      ductal cell clusters assuming a "staghorn" pattern, a feature commonly seen in
      fibroadenoma, were noted. Besides, there were scantly, loose and hypocellular
      stromal tissue fragments that contained spindle cells and occasional paired,
      elongated nuclei embedded in a fibrillary matrix. Histologic examination of the
      excisional biopsies confirmed the presence of PASH. It was characterized by many
      slitlike spaces rimmed by CD34-positive myofibroblasts/fibroblasts in a focally
      hyalinized stroma. Sometimes, ill-formed, fusiform aggregates of fibroblasts were
      also observed. Their fibroblastic nature was confirmed by electron microscopy.
      CONCLUSION: Fine needle aspiration cytology of PASH closely resembles that of
      fibroadenoma. Though subtle differences do exist, a definitive diagnosis is
      unlikely on the basis of the cytologic examination alone. PASH needs to be
      distinguished from borderline lesions, such as phyllodes tumor, and more sinister
      conditions, which sometimes have a similar cytologic appearance.

PMID- 12789919
TI  - Fine needle aspiration cytology of head and neck masses. Seven years' experience
      in a secondary care hospital.
AB  - OBJECTIVE: To study the value of fine needle aspiration (FNA) in the diagnosis of
      head and neck masses in a secondary care hospital. STUDY DESIGN: FNA from 225
      patients with head and neck masses were reviewed. The results were analyzed,
      according to anatomic location, into 3 groups: inflammatory, congenital and
      neoplastic. FNA diagnoses were retrospectively correlated with available
      histologic findings or with the outcome of treatment. Accuracy, sensitivity,
      specificity, positive predictive value and negative predictive value in the
      diagnosis were computed. The numbers of lymph node biopsies performed before and
      after introduction of the procedure were compared. RESULTS: The most common
      diagnoses were reactive/nonspecific lymphadenitis and tuberculous (TB)
      lymphadenitis (33% and 21%, respectively). Sensitivity and negative predictive
      value for TB were 97% and 93%, respectively. The next most common masses were
      malignant neoplasms, cysts, benign neoplasms and sialadenitis, in 13%, 11%, 9%
      and 5%, respectively. Carcinomas metastatic to the lymph node were the most
      common type of cancer, followed by lymphoma and salivary gland carcinoma. The
      primary site of metastatic carcinomas were nasopharynx (44%) and thyroid (22%).
      The sensitivity and negative predictive values for the diagnosis of cancer were
      95% and 96%, respectively, but reached 100% when lymphoma was excluded. The
      introduction of FNA reduced the number of lymph node biopsies performed in this
      hospital by 90%. CONCLUSION: FNA of head and neck masses proved to be a very
      useful diagnostic tool in separating inflammatory lesions (no surgical excision
      required) from cystic and neoplastic lesions. It enhanced surgical planning for
      malignant diseases, allowing rapid referral of lymphomas and cancer cases to
      tertiary care centers for management. FNA is simple, cost effective and suitable
      for developing countries and small, secondary care hospitals with limited
      resources. Skilled personnel and routine audits are the keys to success.

PMID- 12789920
TI  - Value of image-guided needle aspiration cytology in the assessment of pelvic and
      retroperitoneal masses. A study of 112 cases.
AB  - OBJECTIVE: To evaluate the diagnostic value of the noninvasive method of image
      guided needle aspiration cytology (NAC) in the assessment of radiologically
      detected pelvic and retroperitoneal space-occupying lesions (excluding the
      pancreas, kidney and adrenal). STUDY DESIGN: NAC was performed under computed
      tomographic or ultrasound guidance on 112 patients suspected of having a pelvic
      or retroperitoneal mass. Cytologic examination was performed on site after
      staining smears with the Papanicolaou method. In addition, air-dried smears,
      fixed smears, filter preparations from needle washings and cell blocks were
      studied. The NAC diagnosis was supported by examining cell blocks; further
      support was obtained with a tissue biopsy in some cases. Additionally, pertinent
      immunoperoxidase and/or histochemical studies were done. RESULTS: Eighteen cases
      were diagnosed as inflammatory lesions, 17 cases consisted of normal cellular
      elements, and 12 cases showed scanty material and were considered
      unsatisfactory/inadequate for a diagnosis. Five cases were suspicious for
      malignancy, and in 39 cases metastatic tumors were diagnosed from a previously
      known primary. Thirteen cases were diagnosed as lymphoma, and in 8 cases a
      diagnosis of soft tissue sarcoma was made. There were no false positive diagnoses
      of malignancy. Cell block preparations and immunohistochemistry were helpful with
      tumor typing, although lymphoma subtyping and soft tissue tumor typing generally
      required open biopsy. CONCLUSION: NAC, as the first-line investigation, is not
      only useful in the diagnosis of space-occupying lesions of the pelvic and
      retroperitoneal region but can also help in choosing appropriate management. The
      technique is most useful in diagnosing metastases but is also helpful in
      excluding malignancy in some cases and in suggesting diagnoses of lymphomas and
      soft tissue tumors.

PMID- 12789921
TI  - Cytologic features of hyalinizing trabecular adenoma of the thyroid.
AB  - OBJECTIVE: To clarify the cytologic findings of hyalinizing trabecular adenoma
      (HTA) in order to reduce erroneous diagnoses of papillary carcinoma. STUDY
      DESIGN: Review of aspiration cytologic smears of 16 HTA cases and comparison with
      those of 20 papillary carcinoma cases. RESULTS: The smears from HTA were slightly
      cellular, and 5 of 16 cases were insufficient for evaluation. Vague, curved
      nuclear palisading, radiating arrangement surrounding hyaline materials and
      yellow bodies were observed in 9 (81.8%) of 11 cases that had sufficient
      material. The tumor cells were mainly spindled; elongated, polygonal and stellate
      cells were also seen. In 9 of 11 cases, tumor cells with cytoplasmic processes
      were occasionally observed. The cytoplasm was faintly stained and somewhat
      filamentous. The cell border was indistinct. Neither papillary nor follicular
      structures were seen. Intranuclear cytoplasmic inclusions were identified in 100%
      of HTA and 75% of papillary carcinomas. The incidences of nuclear grooves in HTA
      and papillary carcinoma were 81.8% and 100%, respectively. CONCLUSION: Cytologic
      findings indicating HTA are vague, curved nuclear palsiading; radiating
      arrangement surrounding hyaline material; elongated cells; cell processes; ill
      defined cell border; faintly stained and filamentous cytoplasm; yellow bodies;
      and hyaline material in the background. All are useful cytologic characteristics
      in distinguishing HTA from papillary carcinoma. A lack of papillary architecture
      and sheetlike arrangement may also suggest HTA rather than papillary carcinoma.

PMID- 12789923
TI  - Origin of adenocarcinoma cells observed on cervical cytology.
AB  - OBJECTIVE: To clarify the ratio of diseases suspected when malignant glandular
      cells are observed on cervical cytology. STUDY DESIGN: Seventy cases of cervical
      adenocarcinoma/adenosquamous carcinoma, 207 cases of endometrial adenocarcinoma,
      7 cases of tubal adenocarcinoma and 83 cases of ovarian adenocarcinoma were
      reviewed. The positive rate in cervical cytology performed 3 months before
      surgery was calculated. Based on the positive rate for each entity and the number
      of cases treated in the previous 10 years, we estimated the incidence of disease
      responsible for malignant glandular cells on cytology. RESULTS: The positive rate
      was 93% in cervical adenocarcinoma/adenosquamous carcinoma, 45% in endometrial
      adenocarcinoma, 14% in tubal adenocarcinoma and 6% in ovarian adenocarcinoma.
      These positive rates and case numbers at our institute indicated the percentage
      of suspicious diseases to be 38% for cervical aaenocarcinoma/adenosquamous
      carcinoma, 53% for endometrial adenocarcinoma, 1% for tubal adenocarcinoma and 8%
      for ovarian adenocarcinoma. CONCLUSION: When a cytologic specimen suggested the
      existence of adenocarcinoma, the most probable disease was endometrial
      adenocarcinoma, and the second was cervical adenocarcinoma/adenosquamous
      carcinoma. Adnexal malignancies were responsible in 9% of cases. In the case of
      positive cervical cytology suggesting adenocarcinoma, the ratio of suspicious
      diseases is as valuable as the cytologic findings for the differential diagnosis.

PMID- 12789922
TI  - Histopathologic correlation of atypical parakeratosis diagnosed on cervicovaginal
      cytology.
AB  - OBJECTIVE: To retrospectively examine the histopathologic findings in women with
      the isolated finding of atypical parakeratosis (PK) on a Pap test. STUDY DESIGN:
      The cytology files (1999-2001) were searched for cervicovaginal Pap tests
      interpreted as atypical PK. Cases were included for study only if there was a
      subsequent cervicovaginal tissue sample within 1 year of the cytologic
      interpretation and there was no diagnosis of squamous intraepithelial lesion
      (SIL) within the previous five years. RESULTS: Of 355 patients with atypical PK,
      109 (aged 14-69 years, mean 31.5) met the inclusion criteria of the study. The
      interval between the cytologic interpretation and cervicovaginal tissue
      examination ranged from 0.5 to 12 months (mean, 2.5). Sixty-one patients
      underwent both endocervical curettage (ECC) and cervical biopsy (CBx), 20
      patients underwent ECC only, 19 patients underwent CBx only, and the remainder
      underwent other procedures. Histopathologic findings on the tissue samples
      included: no significant pathologic change but no squamous epithelium present for
      evaluation (n = 10, 9.2%), benign changes other than hyperkeratosis and/or PK (n
      = 50, 45.9%), hyperkeratosis and/or PK (n = 8, 7.3%), low grade SIL (n = 33,
      30.3%), high grade SIL (n = 6, 5.5%) and invasive squamous cell carcinoma (n = 2,
      1.8%). CONCLUSION: The isolated finding of atypical PK on a Pap test correlated
      with the presence of an underlying SIL or invasive carcinoma in approximately 40%
      of patients. Of these, 80% had low grade SIL. The cytologic finding of atypical
      PK warrants further investigation in order to exclude SILs and/or carcinoma. We
      suggest that atypical PK be routinely included in the category of atypical
      squamous cells of undetermined significance.

PMID- 12789924
TI  - Introduction of the Bethesda System to Mainland China with a Web-based tutorial.
AB  - OBJECTIVE: To validate the use of a Web-based tutorial to introduce the Bethesda
      System (TBS) to Mainland Chinese laboratories. STUDY DESIGN: Digitized color
      images of the diagnostic features in 20 Pap smears were displayed on a Web page.
      Participants were asked to give each smear a diagnosis using the reporting
      nomenclature employed in their laboratory or one that was familiar to them. This
      was followed by teaching images of each smear accompanied by text in English and
      Chinese that highlighted important features for making a diagnosis using TBS.
      Participants then reviewed the 20 original Pap smears and rendered a diagnosis
      using TBS. RESULTS: Pathologists and cytotechnologists at 17 laboratories located
      in 10 cities completed the exercise. The average diagnostic accuracy for the 20
      Pap smears before and after the tutorial was 76% and 88%, respectively.
      CONCLUSION: Web-based tutorials can be used for disseminating cytologic
      information to widely dispersed laboratories in China and help enhance the
      practice of cytology, currently an underutilized diagnostic technique. However,
      such difficulties as lack of Internet connections in the laboratory, outdated
      computers and a lack of interest in cytology need to be overcome to ensure
      success.

PMID- 12789925
TI  - Nuclear grooves in normal and abnormal cervical smears.
AB  - OBJECTIVE: To determine whether the frequency of nuclear grooves in intermediate
      squamous cells in cervical smears is related to inflammatory or neoplastic
      events. STUDY DESIGN: Sixty benign and 40 neoplastic, nonatrophic cervical
      smears, collected by conventional methods and stained by Papanicolaou stain, were
      selected for this study. Twenty smears of the benign cohort showed evidence of
      inflammation. The neoplastic cohort comprised 20 smears representative of low
      grade and 20 of high grade squamous intraepithelial lesion (LSIL and HSIL,
      respectively), with 50% in each group showing evidence of inflammation. The
      patients, of mixed ethnic backgrounds, were between 18 and 45 years of age. The
      frequency of nuclear grooves in 100 morphologically benign intermediate squamous
      cells were determined in each case. The results were evaluated by statistical
      analysis. RESULTS: The study established that the presence of inflammation had no
      impact on the frequency of nuclear grooves in benign intermediate squamous cells
      in either benign or neoplastic smears. When compared with benign smears, there
      was no increase in the frequency of nuclear grooves in LSIL. Smears of HSIL
      showed the highest frequency of nuclear grooves. The difference between HSIL and
      other groups was statistically significant (P < .01). CONCLUSION: The frequency
      of nuclear grooves in either normal or neoplastic smears is unrelated to
      inflammation. In smears with neoplastic changes, an increase in grooved nuclei
      occurred in HSIL. The mechanism and significance of this observation are unknown
      and warrant further study.

PMID- 12789926
TI  - Multinucleated giant cells in bronchoalveolar lavage.
AB  - OBJECTIVE: To determine the frequency, morphology and possible diagnostic
      significance of multinucleated giant cells (MGC) in bronchoalveolar lavage (BAL).
      STUDY DESIGN: Retrospectively we examined 671 BAL specimens. Enlarged cells
      having > or = 10 nuclei were defined as MGC. Cytomorphologic features were
      described. BAL specimens containing MGC were grouped according to
      clinicohistologic diagnosis into sarcoidosis, asbestosis, other interstitial lung
      diseases and different chronic, noninterstitial lung diseases. RESULTS: MGC were
      present in 10.7% of BAL specimens and occurred in low numbers. MGC were
      classified into Langhans' or foreign-body-type MGC (LF-MGC), alveolar macrophage
      like MGC (AM-MGC) and nonspecific MGC (NS-MGC). LF-MGC were found most often in
      patients with sarcoidosis. AM-MGC were found in all groups of patients. NS-MGC
      were found most often in patients with asbestosis and other interstital lung
      diseases. CONCLUSION: MGC in BAL are not encountered frequently and are not
      numerous. Based on cytomorphologic features, three types of MGC can be
      distinguished.

PMID- 12789927
TI  - Brush cytology of colorectal malignancies.
AB  - OBJECTIVE: To evaluate the specificity and sensitivity of brush cytology and
      biopsy in colorectal malignancies. STUDY DESIGN: The study was performed over 3
      years, 1998-2000. Seventy-six patients with any colorectal lesion on colonoscopy
      were selected, and in all of them brush cytology and biopsy were done at the same
      time. The cytologic smears and biopsies were reviewed separately. The cytologic
      smears were categorized as negative, suspicious, suggestive or positive for
      malignancy. The results of cytology and biopsy were compared based on sensitivity
      and specificity. The gold standard for positive cases was the tissue specimen
      after surgery; negative cases were followed for at least 1 year. Cases with 1
      year of disease-free survival were considered negative. RESULTS: Among 76 cases,
      4 were excluded because of unsatisfactory cytologic smears. Of the remaining 72
      cases, 31 were male and 41 female. The age range was 19-80 years. Cytology showed
      23 positive and 49 negative cases (1 false positive and 3 false negative). Biopsy
      showed 24 positive and 48 negative cases (no false positives and 1 false
      negative). There were 47 negative cases, followed for at least 1 year, and after
      that we considered them definitively negative for malignancy. Sensitivity of
      cytology and biopsy was 88% and 96%; specificity was 98% and 100%, respectively.
      Combined use of brush cytology and biopsy had the highest sensitivity, 100%.
      CONCLUSION: Brush cytology of the colon is a safe, fast and reliable method for
      the diagnosis of colorectal cancer. We recommend performing it in conjunction
      with biopsy. It is also reasonable to perform a repeat biopsy in patients with
      negative biopsy and positive cytology for a definitive diagnosis.

PMID- 12789928
TI  - Reclassification of "atypical" diagnoses in endoscopic retrograde
      cholangiopancreaticography-guided biliary brushings.
AB  - OBJECTIVE: To evaluate the usefulness of reclassifying "atypical" diagnoses in
      reporting biliary cytology using strict morphologic criteria. STUDY DESIGN:
      Cytologic specimens from 139 patients (direct, alcohol-fixed smears or
      cytocentrifuge preparations) were evaluated. Diagnoses were benign (70), atypical
      (36) and malignant (33). Using strict criteria--major (nuclear contour, chromatin
      pattern) and minor (polarity, cell types, nuclear size, nuclear grooves,
      nucleoli, mitosis, nuclear/cytoplasmic [N/C] ratio)--atypical cases were
      reevaluated and reclassified. Follow-up (F/U) was available on all cases.
      RESULTS: Atypical cases, (36) were reclassified as malignant (26), atypical favor
      benign (2)/reactive (3) and atypical, not otherwise specified (NOS) (5). Cases
      reclassified as malignant showed irregular nuclear contours, chromatin
      irregularities and rare mitosis. Nuclear enlargement, nucleoli and cellularity
      varied widely in all groups. N/C ratio was increased in most reclassified
      malignant cases. All 26 malignant reclassifications correlated with F/U of
      malignancy. Benign and reactive cases (5) were negative for malignancy on F/U
      (4), and in 1 case a metastatic carcinoma involving the biliary tree was found.
      In the 5 atypical (NOS) cases, F/U showed malignancy (3) and pancreatitis (2).
      Cytocentrifuge preparations made in our laboratory were of superior quality when
      compared to other methods of cell preparation. CONCLUSION: Irregularities in
      nuclear membrane and abnormal chromatin pattern were the most consistently useful
      features correlating with malignancy. The sensitivity and specificity of biliary
      brush cytology can be enhanced by using strict cytomorphologic criteria and
      proper collection and fixation, all of which decrease atypical diagnoses.

PMID- 12789929
TI  - Comparative analysis of electron microscopy and immunocytochemistry in the
      cytologic diagnosis of malignant small round cell tumors.
AB  - OBJECTIVE: To compare the contributions of electron microscopy (EM) and
      immunocytochemistry (ICC) as adjuncts in the cytodiagnosis of malignant small
      round cell tumors (MSRCT). STUDY DESIGN: This prospective study included 57 cases
      with a preliminary aspiration diagnosis of MSRCT. The contributions of EM and ICC
      in arriving at a specific diagnosis were evaluated. RESULTS: The 57 cases
      included 22 cases of Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), 12
      neuroblastomas, 8 Wilms' tumors, 6 rhabdomyosarcomas, 5 lymphomas, 2
      retinoblastomas and 1 synovial sarcoma. One case remained unclassified. Electron
      microscopy was crucial to the diagnosis in 38.4% cases as against 39.2% of cases
      by ICC. The light microscopic diagnosis was confirmed in 42.3% and 53.5% cases by
      EM and ICC, respectively. EM and ICC were inconclusive for a specific diagnosis
      in 19.2% and 7.1% of cases, respectively. Technically unsatisfactory preparations
      in EM and ICC accounted for 5 and 1 cases, respectively. The overall efficiency
      in making a diagnosis was 80.7% for EM versus 92.8% for ICC. Aberrant expression
      of antigens led to difficulties in interpretation of ICC, and EM was particularly
      helpful. The ultrastructural demonstration of neural differentiation in Ewing's
      sarcoma/PNET tumors helped place tumors in the PNET category. CONCLUSION: While
      ICC is the ancillary method of choice in the cytologic diagnosis of MSRCT, EM
      contributes to the diagnosis and improves diagnostic accuracy.

PMID- 12789930
TI  - Detection of HPV DNA in cervical specimens collected in cytologic solution by
      ligation-dependent PCR.
AB  - OBJECTIVE: To determine the feasibility and sensitivity of detecting human
      papillomavirus (HPV) in specimens collected in Cytyc PreservCyt fluid
      (Boxborough, Massachusetts, U.S.A.) using ligation-dependent polymerase chain
      reaction (LD-PCR) and to demonstrate the diagnostic value of HPV DNA testing as
      an adjunct to cytology in the detection of cervical squamous intraepithelial
      lesions (SIL), especially in cases of atypical squamous cells of undetermined
      significance (ASCUS). STUDY DESIGN: LD-PCR is a recently invented DNA
      amplification technology that utilizes a capture probe for target isolation and 2
      hemiprobes for target detection. The hemiprobes are designed in such a way that
      when they hybridize to their target, the 5' end of one probe and the 3' end of
      the other probe are brought together. Two hemiprobes can then be ligated into a
      full probe that can serve as a template for PCR amplification. A total of 94
      cervical specimens were collected in cytologic fluid and tested with LD-PCR. The
      results were compared with those of the Digene Hybrid Capture II assay (HC II)
      (Beltville, Maryland, U.S.A.) and consensus PCR. RESULTS: The overall sensitivity
      for detecting HPV was 41.5% (39/94) by LD-PCR, 50% (47/94) by consensus PCR and
      37.2% (35/94) by HC II. The prevalence of HPV by HC II, consensus PCR and LD-PCR
      were 87.5%, 100% and 87.5% in the high grade SIL group; 100%, 90.9% and 90.9% in
      the low grade SIL group; 30%, 52.5% and 40% in the ASCUS group; and 14.2%, 22.8%
      and 17.1% in women with normal cytology. These results indicate that all 3
      methods have similar sensitivity in patients with SIL. However, there is greater
      variation in detection rates in the ASCUS and normal cytology groups. CONCLUSION:
      LD-PCR is a useful method of detecting HPV in liquid-based gynecologic cytologic
      preservatives, and HPV testing as a method adjunct to the liquid-based Pap test
      could be useful in detecting SILs, especially for the management of patients with
      ASCUS.

PMID- 12789931
TI  - Transmission electron microscopy of fine needle aspiration biopsies of
      metastases. Accuracy of both techniques as established by biopsy diagnoses.
AB  - OBJECTIVE: To determine the accuracy of fine needle aspiration biopsy in
      establishing the primary on cytology and on cytologic and electron microscopy
      examinations using tissue biopsy as the gold standard. STUDY DESIGN: A
      retrospective study of 96 nonrandomly selected cases of metastases with an
      unknown primary was carried out. Tissue biopsy was performed subsequently for
      confirmation. Proper clinical correlation was part of the analysis. RESULTS: The
      accuracy of cytology in identifying the tumor category (e.g., carcinoma, sarcoma)
      and tumor type (e.g., adenocarcinoma, leiomyosarcoma) was 76% and 78%,
      respectively, while that of electron microscopy was 95% and 91%, respectively.
      The primary site was correctly identified by cytology in 59% and by electron
      microscopy in 88% of cases, provided that clinical parameters were also
      considered. CONCLUSION: Electron microscopy is an ancillary technique useful in
      increasing the accuracy of tumor classification of metastatic neoplasms
      identified by fine needle aspiration biopsy.

PMID- 12789932
TI  - Daily workload guidelines for cytotechnologists utilizing automated, assisted
      screening technologies.

PMID- 12789933
TI  - Metastatic anaplastic oligodendroglioma simulating acute leukemia. A case report.
AB  - BACKGROUND: Anaplastic oligodendroglioma (OG) is an uncommon tumor that rarely
      metastasizes outside the central nervous system. Spread to the bone marrow (BM)
      is so rare that when it occurs in the course of follow-up of a case of OG, a
      disseminated second primary tumor may be a more likely possibility unless BM
      examination provides evidence to the contrary. Potentially misleading cytologic
      features of metastatic anaplastic OG can be seen in a BM touch preparation. CASE:
      A 50-year-old man had undergone left frontal lobectomy in September 1999 for
      anaplastic OG and presented seven months later with evidence, on BM scan, of
      focal abnormal uptake at multiple sites. Bone marrow biopsy confirmed OG
      secondaries, which, on the touch preparation, appeared not only in clusters but
      also as single cells, simulating acute leukemia. CONCLUSION: The morphology of
      anaplastic OG metastatic to BM simulates acute leukemia, as seen on the BM touch
      preparation. This is relevant particularly in the context of anaplastic OG on
      follow-up. This diagnostic pitfall can be heightened if a BM aspirate rather than
      biopsy is performed. Metastatic OG can be added to the list of tumors that
      metastasize to BM as single cells.

PMID- 12789934
TI  - Low grade mucoepidermoid carcinoma arising in cervical lymph nodes. A report of
      two cases with fine needle aspiration findings.
AB  - BACKGROUND: Heterotopic islands of salivary tissue are commonly found in the
      intraparotid lymph nodes and, less commonly, within extraparotid cervical nodes.
      Salivary gland tumors, both benign and malignant, can develop within this ectopic
      salivary tissue. CASES: Two patients presented with a solitary, painless mass in
      the cervical region. Fine needle aspiration cytology was performed, and the
      smears revealed a mixture of intermediate and mucus-secreting cells associated
      with extracellular mucin. The tumors were removed, and the diagnosis of
      mucoepidermoid carcinoma was confirmed by histologic study. CONCLUSION: The
      finding of a malignant cervical salivary gland tumor does not necessarily
      represent a metastasis from an occult site.

PMID- 12789936
TI  - Cytology of pleural effusion associated with disseminated infection caused by
      varicella-zoster virus in an immunocompromised patient. A case report.
AB  - BACKGROUND: Pleural effusion caused by varicella-zoster virus (VZV) is rare. We
      report a case of a woman with acute lymphocytic leukemia (ALL) who developed a
      pleural effusion caused by VZV infection. CASE: A 55-year-old woman with ALL
      treated with consolidation therapy developed skin vesicles and a pleural
      effusion. Pleural fluid smears contained numerous mesothelial cells, which had
      ground-glass nuclei or eosinophilic nuclear inclusions. Some multinucleated giant
      cells were also seen. Electron microscopic examination revealed intranuclear
      virus particles, about 150 nm in diameter, in some mesothelial cells. Tissue
      samples from the skin, lungs, pleura, liver, pancreas, kidneys and
      gastrointestinal tract, obtained at autopsy, contained many virus-infected cells.
      They were positive for VZV glyco-protein 1 by immunohistochemistry. CONCLUSION:
      VZV infection should be considered in the differential diagnosis of an
      unexplained exudative pleural effusion, especially in immunocompromised hosts.

PMID- 12789935
TI  - Primitive neuroectodermal tumor of the kidney. A report of two cases diagnosed by
      fine needle aspiration cytology.
AB  - BACKGROUND: Primitive neurocetodermal tumors (PNETs) constitute a family of
      neoplasms of presumed neuroectrodermal origin most often presenting as bone or
      soft tissue masses. There are very few reported cases of PNET of the kidney and
      none diagnosed by fine needle aspiration cytology (FNAC), to the best of our
      knowledge, in the world literature. We present two cases of renal PNET diagnosed
      on cytology. CASES: Two patients with renal masses were diagnosed as having PNET
      on FNAC. Cytologically the tumors showed a dispersed population of malignant
      small round cells with focal rosette formation and perivascular arrangement of
      tumor cells. Immunohistochemistry on the cell blocks in both cases showed strong
      membrane positivity for CD99 (MIC2). Cytogenetic studies in both cases showed the
      characteristic t(11;22)(q24;q12) translocation, with additional chromosomal
      abnormalities in case 2. CONCLUSION: PNET of the kidney is a distinct entity and
      can be diagnosed on fine needle aspiration smears and confirmed with
      immunohistochemistry and cytogenetic studies. A diagnosis of PNET must be
      included in the differential diagnosis of renal masses in adolescents and young
      adults.

PMID- 12789937
TI  - Fine needle aspiration cytology of neurothekeoma. A case report.
AB  - BACKGROUND: Neurothekeoma (NT) is a rare, benign neoplasm of soft parts with a
      distinctive histologic appearance. To our knowledge, the cytologic findings have
      not been described before. We present a case of NT with the cytologic features on
      fine needle aspiration cytology (FNAC). CASE: A 54-year-old female presented with
      a circumscribed nodule in the left breast. The lesion was evaluated by FNAC. The
      smears showed an abundant, metachromatic, myxoid matrix with fusiform and
      epithelioid cells, some binucleated or multinucleated, loose or in groups and
      sometimes forming concentric whorls. The lesion was removed, and the diagnosis of
      NT was made after histopathologic study. CONCLUSION: NT is an extremely rare
      neoplasm in the mammary region. Fusiform and epithelioid cells arranged in
      concentric whorls in a myxoid tumor of soft tissue are a distinctive
      characteristic of this neoplasm and can suggest the diagnosis.

PMID- 12789938
TI  - Fine needle aspiration appearance of extragastrointestinal stromal tumor. A case
      report.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) rarely develop outside the
      digestive tract and in the soft tissues of abdomen and retroperitoneum. Such
      tumors are designated extra-GISTs (EGISTs). Cytologic and immunocytochemical
      features of a case of EGIST are reported. CASE: A 54-year-old woman presented
      with a peritoneal mass, diameter 22 cm, adherent to the omentum and without a
      connection to the digestive tract. Fine needle aspiration biopsy (FNAB) of the
      excised tumor showed high cellularity in two patterns: monotonous spindle cells
      were intermingled with a mildly atypical epithelioid component.
      Immunocytochemistry performed on cytospins revealed reactivity for c-kit (CD117),
      CD34 and smooth muscle actin and negativity for S-100. The findings were
      concordant with a histologic diagnosis of EGIST. CONCLUSION: EGISTs are
      infrequent neoplasms and can be diagnosed in FNAB samples. The
      clinical/radiologic setting must be considered together with the cytologic
      features. Immunocytochemistry is a clue to the diagnosis when it detects c-kit
      reactivity.

PMID- 12789939
TI  - Synovial sarcoma of the thyroid. Report of a case with aspiration cytology
      findings and gene analysis.
AB  - BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also
      occur in the head and neck region, including the thyroid gland. Cytologic
      findings are important to differentiate the tumor from other types of neoplasms
      arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A
      palpable neck tumor was detected, and a computed tomography scan showed a thyroid
      tumor accompanied by destruction of the thyroid and cricoid cartilage. The
      results of a preoperative fine needle aspiration biopsy showed numerous spindle
      cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of
      which suggested a medullary carcinoma. The extirpated thyroid tissue weighed
      approximately 120 g, and a grayish white, elastic, solid tumor (6.8 x 6.5 cm) was
      present in the left lobe. Histologically, fasciculation of spindle cells that had
      proliferated solidly and densely was observed. Also, the expression of a chimera
      gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of
      the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy
      is generally considered very difficult. The detailed cytologic findings observed
      here might be helpful with the differential diagnosis of thyroid neoplasms.

PMID- 12789940
TI  - Occult lymph node metastasis from desmoplastic small round cell tumor diagnosed
      by fine needle aspiration cytology. A case report.
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare but well
      defined neoplasm generally forming in the abdominal or pelvic cavity of young
      males and has distinct clinical, immunohistochemical and molecular features.
      Cytologic features of DSRCT have been described on fine needle aspiration of
      primary tumors. An occult lymph node metastasis of DSRCT diagnosed through the
      cytologic features, a basic immunocytochemical panel and DNA ploidy evaluation on
      cytospins obtained by fine needle aspiration is reported. CASE: Aspiration
      cytology was performed on an inguinal lymph node from a 20-year-old male. A Diff
      Quik-stained smear showed mature lymphocytes and groups of undifferentiated,
      small cells with scanty cytoplasm, dense and coarse chromatin, and small
      nucleoli. Basic immunocytochemical stains showed negativity for leukocyte-common
      antigen and neuron-specific enolase and positivity for cytokeratin cocktail (Cam
      5.2), vimentin and desmin, the last with characteristic paranuclear dotlike
      positivity. DNA ploidy evaluation showed an aneuploid histogram with a low 5c
      exceeding rate. CONCLUSION: Cytologic and immunocytochemical features suggest the
      diagnosis of DSRCT on fine needle aspiration cytology samples even in cases of a
      metastatic, unknown primary tumor. Because of the tumor's aggressiveness, a rapid
      and accurate diagnosis is required.

PMID- 12789942
TI  - Fine needle aspiration cytology findings of cystic hypersecretory ductal
      carcinoma of the breast: a reappraisal.

PMID- 12789941
TI  - Intracranial hydatidosis. Report of a case diagnosed on cerebrospinal fluid
      cytology.
AB  - BACKGROUND: Hydatidosis occurs due to infestation with the larval stage of the
      Echinococcus species. Humans are incidental hosts. Symptoms and signs in humans
      are a slowly growing mass lesion, especially in the central nervous system.
      Diagnosis depends on the appropriate presentation and history with corroborative
      radiology and serology. Microscopic detection of characteristic parasitic
      scolices and hooklets is confirmatory. CASE: A 10-year-old girl presented with
      complaints of headaches and convulsions for the preceding several months.
      Computed tomography findings showed asymmetric dilatation of the right lateral
      ventricle by an intraventricular, focally calcified mass. The radiologic
      suspicion was an intraventricular tuberculoma, hydatid cyst or choroid plexus
      papilloma. Cytologic examination of cerebrospinal fluid (CSF) smears revealed
      characteristic echinococcal components. CONCLUSION: Intracranial hydatid cyst is
      a fairly uncommon manifestation of an echinococcal infestation and shares
      clinicoradiologic features with several intracranial, space-occupying lesions.
      Cytologic examination of CSF samples may be employed to detect confirmatory
      evidence of a clinical/radiologic suspicion.

PMID- 12789943
TI  - Nodal neuroendocrine (Merkel cell) carcinoma without an identifiable primary
      tumor.

PMID- 12789944
TI  - Malignant transformation of a well-differentiated peritoneal papillary
      mesothelioma.

PMID- 12789945
TI  - Cytology of subependymoma.

PMID- 12789946
TI  - Immunocytochemical analysis of fine needle aspiration cytology to improve
      surgical strategy in thyroid neoplasms.

PMID- 12789948
TI  - Fine needle aspiration cytology of a cutaneous bronchogenic cyst.

PMID- 12789947
TI  - Diagnosis of chondroid syringoma by fine needle aspiration cytology.

PMID- 12789949
TI  - Fine needle aspiration cytology of pilomatrixoma of the neck region:
      differentiation from metastatic undifferentiated nasopharyngeal carcinoma.

PMID- 12789950
TI  - A rare case of cryptococcosis diagnosed by fine needle aspiration cytology.

PMID- 12789951
TI  - Histoid leprosy: diagnosis by fine needle aspiration cytology.

PMID- 12789952
TI  - Testicular germ cell tumor metastatic to the retina: vitreous fluid cytologic
      findings.

PMID- 12789953
TI  - Implications of child development on the practice of oral care.
AB  - Of all patient groups, children represent perhaps the most challenging in the
      preventive dental practice. While technical skills must be excellent, the
      interpersonal skills of the clinician are also paramount to successful pediatric
      dentistry and are affected by where children are in their development. This
      article reviews the developmental stages that children experience and how age
      characteristics can be predictors of the dental professional's approach to ensure
      successful, long-term oral health care.

PMID- 12789954
TI  - The hygienist's role in improving children's oral health throughout their
      development.
AB  - Improving oral hygiene in children is one of the most challenging aspects of the
      preventive dental practice because their dentition, dexterity, and emotional
      maturity are simultaneously developing. This article discusses the role of the
      hygienist in providing oral health care and education in the context of
      developing preventive care programs that can be tailored to meet the needs of
      children in different age groups. Particular attention will be given to
      identifying proven approaches to motivating children and their parents to respond
      positively to oral health advice and hygiene instruction.

PMID- 12789955
TI  - A practice based evaluation of a range of children's manual toothbrushes: safety
      and acceptance.
AB  - Toothbrushes for children have not suited all age groups. The development of a
      series of children's toothbrushes (Oral-B Stages toothbrushes) targeted at four
      age-defined groups and designed to meet their needs offers the potential to
      enhance oral hygiene. To obtain information regarding the specific likes and
      dislikes of these four children's toothbrushes, a randomized, practice based
      study involving children between the ages of 4 months and 11 years was conducted.
      Children were recruited from 25 pediatric dental practices located in the United
      States, Australia, and Europe. After 1 month of using the brushes, questionnaires
      were completed by the parents or guardians, children, and dental professionals.
      Eighty percent to 90% of respondents "liked" or "liked extremely" the
      toothbrushes with respect to overall like or dislike, cleaning ability, ease of
      use, and gentleness. Ninety-five percent of the dental professionals in the study
      concluded that they would recommend these toothbrushes to their patients and 90%
      thought that the toothbrushes would improve their patients' oral health. It was
      concluded that the four children's toothbrushes are safe and effective. The
      design of the brush heads should enhance plaque removal while the ergonomic
      design of the handles will aid dexterity.

PMID- 12789956
TI  - A practice based study of a children's power toothbrush: efficacy and acceptance.
AB  - Power toothbrushes can offer significant advantages over a manual toothbrush both
      with respect to plaque removal and compliance. Most studies have, however, been
      carried out with adult toothbrushes in adult populations. Less is known about the
      efficacy of children's power toothbrushes, although it is likely that similar
      advantages will be demonstrated. This practice based study used the Debris Index
      (DI) component of the Simplified Oral Hygiene Index to compare baseline oral
      hygiene with results after 2 months of using the Braun Oral-B Kids' Power
      Toothbrush (D10). The study involved 13 dental offices and a total of 154
      children aged 4 to 9 years. For all sites (facial and lingual), using the D10 for
      2 months resulted in an approximately 40% reduction in the DI. Questionnaires
      completed by the parents or guardians, the children, and the dentists indicated a
      very favorable response to the power toothbrush. Both parents and children
      preferred the D10 to a manual toothbrush and most said they would continue to use
      it. The fact that children found the D10 fun to use may well aid compliance.
      Dentists thought that the D10 was effective and, at the end of the study, most
      said that they would now recommend a power toothbrush. It is concluded from the
      results of this practice based study that the D10 can help to reduce plaque
      levels in a population of children who previously relied on a manual toothbrush.
      The fact that the D10 is appealing to children and fun to use should aid
      compliance with long-term oral hygiene.

PMID- 12789957
TI  - Immediate implant placement and temporization in extraction and healing sites.
AB  - While single tooth replacement can be predictably accomplished using implant
      therapy, this procedure is challenging in the esthetic zone where numerous
      criteria must be evaluated by the restorative team. If the gingival and osseous
      architecture of the failing tooth is acceptable, the therapeutic goal is to
      maintain the existing morphological condition. The optimal tridimensional implant
      is placed in the esthetic zone immediately after extraction or 8 to 12 weeks
      after extraction. The abutment connection and the nonfunctional temporary tooth
      restoration are prepared in advance and should respect the forms of contour of
      the contralateral tooth. In some specific clinical cases, not only can the
      patient's smile be returned after only a few hours of clinical work, but more
      importantly, initial capital of soft and hard tissues can be preserved. After
      healing, maturation, and stabilization during the 3 to 6 months of
      osseointegration, a compressive impression of the implant site can be taken and
      the implant restoration can be cemented. A multi-centric study performed by
      several dentists during the past 3 years have drawn interesting statistics on the
      rate of success, the different type of implants, and the variation of the peri
      implant bone and gingival contour.

PMID- 12789958
TI  - Reinforced core build-up materials.

PMID- 12789960
TI  - An auto-mixing resin ionomer cement.

PMID- 12789959
TI  - Clinical evaluation of a 35% hydrogen peroxide in-office whitening system.
AB  - This study evaluated the effectiveness of light-curing (heat conversion) vs no
      light-curing (no heat conversion) of a 35% hydrogen peroxide in-office tooth
      whitening system. Twenty patients with sound medical history (without tooth
      sensitivity) participated in this randomized, parallel clinical evaluation. Only
      six maxillary anterior teeth with discoloration and a tooth shade of A3 or darker
      were selected. Patients received a complete prophylaxis and were evaluated for
      initial (baseline) shade by three independent evaluators, precalibrated at 85%
      rater reliability in determining shades before the experiment began. Participants
      received a 20-minute chairside whitening treatment with a 35% hydrogen peroxide
      agent using a reflective resin barrier for gingival isolation. During the
      whitening treatment, the 35% hydrogen peroxide agent was light-activated with a
      halogen curing light on teeth Nos. 6 through 8 (Group I), but was not light
      activated on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours
      after the whitening application for shade evaluation. Although there were
      isolated instances (7 out of 20 patients) of greater degrees of lightening in the
      light-curing group, there was no statistically significant difference using the
      Mann-Whitney U test (P > .05). This study indicates that light-curing is optional
      with this 35% tooth whitening system.

PMID- 12789961
TI  - Treatment of the infected implant site using platelet-rich plasma.
AB  - Implant therapy has become a highly effective treatment modality for patients
      seeking the replacement of lost dentition. Potential complications in the
      delivery of implant therapy may cause either failure of implant integration or
      the development of peri-implantitis. In an effort to enhance the healing phase in
      the treatment of the infected implant site, the incorporation of platelet-rich
      plasma and its growth factors has been introduced into the surgical protocol.
      Documentation of cases requiring the treatment of infected implant sites with
      combined bone grafting, tissue regeneration, and enhanced healing phase
      management with platelet-rich plasma is presented.

PMID- 12789962
TI  - A century of progress in understanding periodontal disease.
AB  - Throughout the 20th century, investigators and clinicians sought to discover the
      causes and trace the natural history of periodontal disease. Noteworthy progress
      has been made on several fronts. It was once believed that oral hygiene and age
      accounted predominantly for variances in the prevalence and severity of
      periodontal disease; now, a number of innate, acquired, and environmental risk
      factors have been identified. Light has been shed on the roles in periodontal
      disease pathogenesis of both specific bacteria and bacterial complexes and host
      immunoinflammatory responses. Insight into periodontal wound healing has fostered
      promising approaches to promoting regeneration of damaged periodontal structures.
      Finally, although theories of "focal infection" as a primary cause of systemic
      disease have been discredited, recent studies have confirmed the existence of an
      intimate connection between oral and systemic health. The progress made in
      understanding the nature of periodontal disease has been complemented by equally
      noteworthy therapeutic advances. The coupling of surgical and medical approaches
      to treatment ushers in a new era in the management of periodontal disease.

PMID- 12789963
TI  - The etiology and pathogenesis of periodontitis.
AB  - Major advances have been made in our basic understanding of periodontal disease
      during the last decade. Pathways whereby bacteria destroy the periodontal
      connective tissues and alveolar bone have been elucidated. The manner in which
      various risk factors alter these pathways to enhance risk and amplify the onset
      and progression of disease is becoming clearer. Furthermore, a strong link
      between periodontitis and potentially fatal systemic diseases and conditions has
      been demonstrated. These advances in knowledge have led to the development of new
      approaches to treatment that enhance our capacity to prevent and control oral
      infections and to decrease potential systemic disease consequences.

PMID- 12789965
TI  - Putting science into practice: the clinical translation of medical approaches.
AB  - Proving a relationship between inflammatory periodontal disease and systemic
      disease will bring significant changes to the average periodontal practice.
      First, there will be a time of confusion with competing ideas and techniques.
      Determination of acceptable levels of inflammation will bring an end to the
      discussion. As this transition occurs, patients will need to be kept as current
      as possible without being unnecessarily alarmed. The average periodontal practice
      will shift its emphasis toward controlling inflammation. Initially, this will
      mean more periodontal surgery, more tooth extraction, and more implant placement.
      In the long run, periodontal disease may be treated by the patient with anti
      inflammatory medications; by the general dentist with local therapy including
      antibiotics and anti-inflammatory medications, advanced nonsurgical techniques,
      and surgery; and, less frequently, by the periodontist.

PMID- 12789964
TI  - Minocycline microspheres: a complementary medical-mechanical model for the
      treatment of chronic periodontitis.
AB  - Locally delivered antimicrobials represent an expanding class of therapeutics
      that may complement conventional mechanical treatments for chronic periodontitis.
      Currently available locally delivered antimicrobials include a tetracycline
      fiber, chlorhexidine chip, doxycycline gel, and newly approved minocycline
      microspheres. This last therapeutic is formulated to contain 3 mg polyglycolide
      co-dl lactide (PGLA) copolymer and 1 mg of minocycline per unit (pocket) dose. As
      the polymer microspheres resorb, minocycline is released locally within the
      periodontal pocket at effective concentrations for at least 14 days. Recently,
      three phase 3 human clinical trials were conducted to assess the efficacy and
      safety of minocycline microspheres in patients with moderate-to-advanced chronic
      periodontitis. Data from an open-label trial involving 173 subjects indicated
      that minocycline microspheres plus scaling and root planing (SRP) at baseline
      produced significant improvements in pocket depth (PD) (> or = 1.5 mm) at 1 and 3
      months. Retreatment with minocycline microspheres at 3 and 6 months maintained
      these improvements for 12 months. Two concurrent, blinded studies cumulatively
      recruited 748 periodontitis subjects who were randomized to SRP plus minocycline
      microspheres, SRP plus vehicle (placebo), or SRP alone at baseline. Minocycline
      microspheres or the vehicle were readministered per the randomization at 3 and 6
      months. Patients receiving minocycline microspheres plus SRP exhibited
      significantly greater PD reduction at 1, 3, 6, and 9 months compared to patients
      receiving SRP plus vehicle or SRP alone. Overall, mean PD reduction with
      adjunctive minocycline-microsphere treatment increased when patients with more
      advanced periodontitis (mean PD > or = 6 mm or 7 mm) were considered. Similarly,
      significant improvements in clinical attachment level and percent bleeding on
      probing were observed among advanced periodontitis patients treated with SRP plus
      minocycline microspheres relative to controls. Patients treated with minocycline
      microspheres plus SRP were 50% more likely to shift to an overall mean PD < 5 mm
      or to a more maintainable case definition. No increased incidence of adverse
      events or tetracycline resistance were observed with minocycline-microsphere
      treatment. The data from these clinical trials indicate that minocycline
      microspheres plus SRP are safe in patients and more effective than SRP alone in
      reducting the signs of chronic periodontitis.

PMID- 12789966
TI  - Biological mediators for periodontal and bone regeneration.
AB  - In the past 25 years, significant advances in treatment have occurred in the area
      of periodontal and bone regeneration. Novel regenerative therapies have emerged
      based on an increased understanding of embryonic development and wound healing at
      the cellular and molecular level. Two approaches that have demonstrated
      significant regenerative potential include the administration of enamel matrix
      proteins and growth and differentiation factors. Current data regarding the use
      of enamel matrix proteins support their safety and efficacy. The use of
      recombinant growth and differentiation factors has been validated in preclinical
      and clinical trials. A new era of regenerative therapies has emerged, using
      biological mediators combined with scaffold materials to stimulate cellular
      processes required for the regeneration of oral tissues. The clinical application
      of these therapies will be to either replace or augment traditional regenerative
      treatments.

PMID- 12789967
TI  - Management of complicated crown fractures: tooth fragment reattachment.

PMID- 12789968
TI  - The effect of four mouthrinses on oral malodor.
AB  - The purpose of the study was to compare the efficacy of four mouthrinses in
      clinical outcomes of changes in oral malodor measurements in a 4-week,
      randomized, double-blind, longitudinal clinical trial in adults. The four rinses
      were coded as Products 1, 2, 3, and 4 so that neither the examiners nor subjects
      had the knowledge of treatment. Of the four mouthrinses, two were commercially
      available mouthrinses with essential oils (EO) or chlorine dioxide plus zinc
      (CD/Zn) as active ingredients (Products 1 and 4), one mouthrinse was a
      formulation containing cetylpyridinium chloride (Product 2), and one was a
      placebo (Product 3). A total of 99 subjects who met the study criteria were
      assigned randomly to one of the four groups. At three separate visits (0, 2, and
      4 weeks), subjects received an examination of the oral soft tissues and were
      assessed for baseline oral malodor by two organoleptic judges and a laboratory
      instrument that measures oral malodor. Subjects were instructed to use the
      assigned rinse, and the measurements were performed again after 2 and 4 hours.
      Throughout the 4-week study period, each subject was asked to use the assigned
      rinse twice daily per the manufacturer's recommended directions. The results
      showed that the four mouthrinses reduced oral malodor within 4 hours after a
      single usage, with Product 2 being the most effective and the placebo being the
      least effective. Daily use of EO, CD/Zn, and placebo rinses for up to 4 weeks did
      not reduce oral malodor from week 0 baseline values, and the effects on oral
      malodor were comparable among these three mouthrinses. Product 2 was the only
      mouthrinse that reduced oral malodor from baseline values after 2 and 4 weeks of
      daily use.

PMID- 12789969
TI  - Bonded resin-based composite crown restoration of diminutive lateral incisors.

PMID- 12789970
TI  - Management of occupational exposure to hepatitis B, hepatitis C, and human
      immunodeficiency virus.
AB  - The primary focus in occupational injury management is the prevention of injuries
      before they take place through standard precautions, personal protective
      equipment, and administrative, work practice, and engineering controls. However,
      should an exposure occur, prompt and appropriate response may reduce the risk of
      bloodborne pathogen transmission. The Centers for Disease Control and Prevention
      (CDC) recently released an updated guideline for postexposure management after
      occupational exposure to hepatitis B, hepatitis C, or human immunodeficiency
      virus. This article reviews the steps that should be taken to prevent exposure to
      bloodborne pathogens as well as the appropriate response in the event of an
      exposure. In addition, the CDC's updated guidelines for postexposure management
      will be reviewed.

PMID- 12789971
TI  - Dental practice slowdown--a case study.

PMID- 12789972
TI  - Direct composite resins: an update.
AB  - Esthetic restorative materials require a bonding procedure to achieve durability
      and reliability. To accomplish this, the bonding system and restorative material
      must be biocompatible and bond well to both dentin and enamel. The direct
      restorative must have sufficient strength to resist masticatory forces as well as
      mechanical properties close to those of natural tooth structure. These materials
      should be resistant to degradation in the oral cavity and easy to use. This
      article reviews the published literature on direct composite restorative
      materials.

PMID- 12789973
TI  - Indirect composite restorations: alternative or replacement for ceramic?
AB  - In esthetic restorative dentistry, many new materials have been developed in
      recent years. These materials are often promoted with little clinical research
      and dentists use these materials on the recommendations of their peers or simply
      because they are new. It is the author's opinion that supportive clinical
      research should be examined before any material can be used with absolute
      confidence. In the absence of supportive research, there must be sufficient
      justification for trying new materials. It is the purpose of this article to
      examine the possible uses of indirect composite in esthetic restorative dentistry
      and to evaluate whether or not their use is advantageous over the use of ceramic
      materials.

PMID- 12789974
TI  - A cementable, all-ceramic restorative system.

PMID- 12789975
TI  - CAD/CAM systems, materials, and clinical guidelines for all-ceramic crowns and
      fixed partial dentures.
AB  - Advances in dental ceramic materials and the development of computer-aided
      design/computer-aided manufacturing (CAD/CAM) and milling technology have
      facilitated the development and application of superior dental ceramics. CAD/CAM
      allows the use of materials that cannot be used with conventional dental
      processing techniques. This article reviews the main techniques and new materials
      used in dentistry for CAD/CAM-generated crowns and fixed partial dentures. Also
      covered are the clinical guidelines for using these systems.

PMID- 12789976
TI  - Clinical evaluation of etched porcelain onlays: a 4-year report.
AB  - Etched porcelain-bonded-to-enamel restorations (porcelain veneers) have
      demonstrated a low incidence of debonding, fracture, microleakage, and
      discoloration. In addition, laboratory and short-term clinical studies have shown
      satisfactory results with posterior etched porcelain-bonded restorations. This
      study evaluated the 4-year clinical performance of posterior all-ceramic onlays
      and overlays bonded with a dual-cure luting resin and a self-cure acetone-based
      dentinal adhesive. Twenty-one posterior porcelain overlay restorations were
      fabricated from a high-leucite-content porcelain and bonded to the teeth of 12
      adults using a dual-cure luting resin and an acetone-based self-cure N(P-tolyl)
      glycine-glycdyl methacrylate (NTG-GMA), pyromellitic acid dianhydride and 2
      hydroxyethyl methacrylate (PMDM) dentinal adhesive. Restorations were examined
      for retention, marginal caries, marginal microleakage, sensitivity,
      discoloration, restorative fracture, and patient satisfaction. Data collected at
      4 years revealed 100% retention of the restorations with no marginal
      discoloration, marginal ditching, caries, or sensitivity. A small gap (Ryge UPHS
      rating of Bravo) was detected at the facial margin of one restoration but was not
      sufficient enough to require repair or replacement. Each patient reported a very
      high level of satisfaction with the restorations. This study demonstrates that
      porcelain overlays with supragingival margins entirely on enamel that rely
      primarily or entirely on bonding for their retention can provide excellent
      esthetics, good function, and perhaps long-term durability if properly designed,
      fabricated, and bonded. Porcelain overlays fabricated from high-leucite-content
      porcelain bonded to sound enamel and dentin with a dual-cure luting resin and a
      fourth generation dentinal adhesive provide satisfactory clinical results and
      high patient satisfaction.

PMID- 12789978
TI  - Impact of the sonicare toothbrush on plaque and gingivitis.
AB  - The sonicare toothbrush has been shown to be 40% more effective in removing
      plaque than a manual toothbrush, 82% better in removing plaque from interproximal
      areas, and to reverse gingivitis. In vitro studies have examined the ability of
      the sonicare toothbrush to remove plaque bacteria beyond the reach of the
      bristles. The sonicare toothbrush has also been shown to produce significantly
      less dentin wear in vitro than another leading power toothbrush. This article
      reviews both in vivo and in vitro studies that illustrate the efficacy of the
      sonicare toothbrush in improving oral health.

PMID- 12789977
TI  - Dental plaque as a biofilm and new research on biofilm removal by power
      toothbrushes.
AB  - Dental researchers have only recently begun to regard dental plaque as a biofilm.
      Dental plaque biofilm is a complex, heterogeneous structure of bacteria cells, a
      sticky extracellular matrix, and fluid channels. The biofilm must be modeled
      accurately for laboratory studies to be meaningful. To that end, researchers have
      compared the sonicare toothbrush to the Braun Oral-B 3D Excel Plaque Remover for
      the removal of interproximal dental plaque biofilm in an in vitro model. This
      article defines the concept of biofilms in the oral cavity and reviews how
      biofilm modeling is showing differences in toothbrush performance.

PMID- 12789979
TI  - Effects of the sonicare toothbrush for specific indications.
AB  - The sonicare toothbrush has been shown to reduce plaque and gingivitis better
      than a manual toothbrush among orthodontic patients. The sonicare toothbrush has
      also been shown to reduce pocket depths in patients with periodontitis. Use of
      the sonicare toothbrush reduced hypersensitivity after 8 weeks of use and removed
      82% of the extrinsic stain from coffee, tea, and tobacco after 4 weeks of use. It
      has also been shown to be as effective as or better than a manual toothbrush for
      reducing plaque and gingivitis around dental implants and to increase salivary
      flow in xerostomia patients.

PMID- 12789980
TI  - Clinical aspects of recurrent oral herpes simplex virus infection.
AB  - Recurrent oral ulcerations are the most common pathologic condition seen by
      general dentists. Because the etiology of oral ulcers is diverse, it is a
      continuous challenge for clinicians to reach a correct diagnosis. Recurrent
      herpes simplex virus (HSV)-associated ulcerations mainly affect the lip (herpes
      labialis). However, intraoral ulcerations may also be a sign of recurrent
      disease. For many patients, these sores are painful and unsightly. Up to 85% to
      90% of adults show serologic evidence of exposure to HSV. HSV infections can
      cause high morbidity beyond oral and genital lesions. Furthermore, HSV poses an
      infectious risk to both patients and oral health care providers, so it is
      important that dental professionals are up-to-date on appropriate therapies and
      precautions. This article discusses recurrent oral HSV infection and nonoral
      manifestations of HSV infection.

PMID- 12789981
TI  - Recurrent herpes labialis: current treatment perspectives.
AB  - Recurrent herpes simplex infection of the lips and perioral skin is a very common
      problem in the general population, often leading patients to seek diagnostic and
      therapeutic intervention from their dental practitioner. Mechanisms for viral
      reactivation are well known and have led to the development of new classes of
      systemic and topical drugs that have been shown to be clinically effective in
      reducing recurrence frequency and duration. This article presents current
      treatment choices within the context of healthy and immunocompromised patients,
      as well as more traditional therapies.

PMID- 12789982
TI  - Exploring evolutions in dental handpieces.
AB  - The introduction of a variety of contemporary esthetic and restorative materials
      has resulted in numerous improvements in the techniques employed throughout the
      entire restorative process that were historically taught in schools. As a result,
      the equipment designs and hand instrumentation have evolved to offer clinicians
      higher efficiency and better physical delivery of quality dental care.

PMID- 12789983
TI  - Case selection criteria and a simplified technique for placing and finishing
      direct composite veneers.
AB  - This article addresses the key obstacles clinicians face when considering direct
      composite veneers as a treatment option for the cosmetic correction of anterior
      teeth. These obstacles include case selection, material selection, the best
      technique to allow the expeditious placement of the veneers, and, ultimately,
      final esthetics. The best clinical situations for choosing direct composite
      veneers are identified, and a new microhybrid composite resin system, Esthet-X,
      which offers a simplified solution to shade matching and polishing, is
      introduced. A clinical case demonstrates a simplified technique for the placement
      of stratified, polychromatic direct veneers, and describes a new polishing system
      that generates a microfill type of shine with modern microhybrids.

PMID- 12789985
TI  - A new metal-free alternative for single- and multiunit restorations.
AB  - More than 40 years after their development, porcelain-fused-to-metal (PFM)
      restorations remain the clinical standard against which other esthetic dental
      materials are measured. One of the challenges of PFM restorations, as with many
      indirect restorations, is the task of making them appear lifelike when viewed
      adjacent to natural teeth. All-ceramic restorations have become a welcome
      addition to the restorative armamentarium because their lack of a metal
      substructure allows them to blend well with surrounding natural dentition. While
      all-ceramic materials were initially used to veneer teeth and improve esthetics,
      they began to be used for full-coverage crowns and, more recently, to replace
      missing teeth as well.

PMID- 12789984
TI  - Light-curing technology: past, present, and future.
AB  - The availability of light-curable resin systems has led to the development of a
      variety of technologies for producing the light necessary to cure them. Light,
      being electromagnetic radiation, is comprised of a wide spectrum of energies
      including ultraviolet, visible, and infrared. Each wavelength region of light has
      different characteristics in terms of chemical reactions, most notably
      polymerization of dental materials. Quartz tungsten halogen, plasma arc curing,
      laser, and, recently, light-emitting diode have all been important technologies
      used to produce light through dental curing units. Each technology has unique
      advantages and disadvantages. Thus, it is important for dental professionals to
      understand the polymerization processes and the ways in which these processes are
      affected by light energy.

PMID- 12789986
TI  - A clinician's 3-year experience with perioscopy.
AB  - A medical endoscope has been modified for assisting the clinician in subgingival
      scaling and root planing. The dental endoscope provides real-time indirect
      visualization of the root surface for aiding the removal of root deposits and
      biofilm. When the majority of biofilm and visible calculus is removed from the
      root surface in a periodontal pocket, the pocket will most often close, resulting
      in a shallow sulcus. Many lesions on single-rooted teeth can be treated
      successfully with this technique, resulting in a significant reduction in
      probable pocket depth and a gain in the calibrated attachment level. Other sites,
      such as furcations and maxillary first bicuspids, may demonstrate significant
      improvement but not complete resolution of these parameters. Perioscopy is
      scaling and root planing aided by indirect vision with an endoscope. This
      technique can offer many patients an alternative to periodontal surgery in
      carefully selected sites. This article describes the clinical rationale for
      perioscopy, defines those sites that most predictably will respond to this mode
      of therapy, and offers some guidelines on integrating this technology into the
      dental practice. The observations and recommendations in this article are based
      on the author's 3-year experience with the dental endoscope in his periodontal
      practice, the experience of other periodontists and dental hygienists, and
      published reports.

PMID- 12789987
TI  - Clinical applications for host modulatory therapy.
AB  - A better understanding of the pathogenesis of periodontitis has resulted in
      pharmacotherapeutic advancements that address both the microbes and the host
      response, leading to improved management of this chronic progressive disease by
      the dental practitioner. The adjunctive use of host modulatory therapy can
      enhance therapeutic responses, slow the progression of the disease, and allow for
      more predictable management of patients, particularly in those patients at
      increased risk caused by factors beyond the reach of conventional therapeutic
      approaches. This article reviews the pathogenesis and risk factors associated
      with periodontitis and addresses, in detail, the concept and clinical use of host
      modulation as a therapeutic strategy.

PMID- 12789988
TI  - Conceptualization vs reality in periodontal therapy: genetic testing and host
      modulation.
AB  - This article addresses controversial issues associated with two different
      subjects: reliability of a genetic susceptibility test to identify individuals
      predisposed to developing periodontitis; use of subantimicrobial-dose doxycycline
      in the treatment of periodontal diseases. Each subject is assessed with regard to
      its practical application in the management of patients with chronic
      periodontitis.

PMID- 12789989
TI  - Laser curettage: an overview.
AB  - The literature suggests that subgingival curettage has no benefit beyond
      traditional scaling and root planing. In addition, mounting evidence suggests
      that there is a risk of clinically significant collateral damage to using Nd:YAG
      laser energy within the sulcus. There also appears to be some confusion regarding
      the standards of evidence upon which to judge the performance of adjunctive
      procedures such as laser curettage. This article presents a review of the
      literature and a synopsis of the current scientific consensus regarding laser
      curettage, its effectiveness, its potential for collateral damage, and the
      scientific standards that apply.

PMID- 12789990
TI  - Lasers and soft tissue curettage: an update.
AB  - This article describes how certain dental laser instruments are used adjunctively
      in the initial phase of the treatment of periodontal disease. The author explains
      the fundamentals of laser science and tissue interaction and lists the steps of
      the clinical protocol. Examples of treated clinical cases are shown, and the
      safety and effectiveness of this instrumentation are discussed.

PMID- 12789991
TI  - Safety profile of a new liquid whitening gel.
AB  - Colgate Simply White Clear Whitening Gel, an at-home tooth-whitening product
      purchased over the counter, contains 18% carbamide peroxide (equivalent to 6.5%
      hydrogen peroxide) as the active ingredient in a brush-applied liquid gel. The
      excipients include ingredients commonly used in dentifrices. The potential for
      effects on the tooth pulp, oral soft tissue irritation, enamel damage, and tooth
      sensitivity with this peroxide-containing product have been evaluated. An in
      vitro study demonstrated that pulpal chamber hydrogen peroxide levels are well
      below those considered to cause an effect on pulpal tissue. An exaggerated-use (4
      applications per day for 3 weeks) clinical study showed that no oral irritation
      occurred during 3 weeks of use. A study measuring peroxide salivary concentration
      after use of Colgate Simply White Clear Whitening Gel showed that the
      concentration of peroxide in the saliva after use of the product was extremely
      low, further supporting the position that this product has a low potential for
      causing oral irritation. Additional studies demonstrate that Colgate Simply White
      Clear Whitening Gel does not harm the enamel surface or produce demineralization
      after exposure equivalent to 3 weeks of normal use and over 6 weeks of
      exaggerated use. Colgate Simply White Clear Whitening Gel has not produced oral
      irritation (hard and soft tissues) or tooth hypersensitivity in a clinical
      subject population of 141 individuals using varying treatment regimens. These
      studies prove that Colgate Simply White Clear Whitening Gel is safe for daily use
      as directed.

PMID- 12789992
TI  - Comparative 3-week clinical tooth-shade evaluation of a novel liquid whitening
      gel containing 18% carbamide peroxide and a commercially available whitening
      dentifrice.
AB  - A randomized, controlled, examiner-blind, parallel-group clinical trial was
      performed to compare the tooth-whitening benefits of a novel, nontray, "paint-on"
      liquid gel containing 18% carbamide peroxide (Colgate Simply White Clear
      Whitening Gel) to those of a commercially available whitening dentifrice.
      Efficacy was measured by using Vita shade scores obtained at baseline and after 2
      and 3 weeks of product use. Eighty subjects were first balanced according to
      gender, age, and shade scores into two groups. Half were then randomly assigned
      to either alpha 3-week routine of tooth-brushing (using a nonwhitening
      dentifrice) and twice-daily 18% carbamide peroxide gel application or a 3-week
      routine of twice-daily brushing with the commercially available whitening
      dentifrice. At the completion of the study, the results showed that subjects'
      teeth in the liquid whitening gel-treated group exhibited a statistically
      significant (P < .05) 4.12 mean tooth-shade improvement compared to baseline and
      exhibited a mean score that was 3.7 units higher than the corresponding mean
      score of the group assigned to use the whitening dentifrice (statistically
      significant, P < .05). It can therefore be concluded that the combined use of
      Colgate Simply White Clear Whitening Gel immediately after brushing with a
      regular toothpaste is clinically superior at whitening teeth than solely using a
      clinically proven, commercially available whitening dentifrice.

PMID- 12789993
TI  - Clinical comparison of the stain-removal efficacy of a novel liquid whitening gel
      containing 18% carbamide peroxide and a commercially available whitening
      dentifrice.
AB  - The objective of this examiner-blind clinical study was to compare the extrinsic
      tooth-stain removal efficacy of a novel, nontray, "paint-on" liquid whitening gel
      containing 18% carbamide peroxide (Colgate Simply White Clear Whitening Gel) with
      a commercially available whitening dentifrice. After a baseline examination for
      extrinsic tooth stain, qualifying adult men and women from Canada were randomized
      into two treatment groups balanced for age, gender, and level of extrinsic tooth
      stain. Subjects were instructed to brush their teeth twice daily (morning and
      evening) for 1 minute with their assigned dentifrice (Group 1: nonwhitening
      dentifrice; Group 2: whitening dentifrice). The subjects in Group 1 also were
      instructed to use the paint-on whitening gel for 30 minutes twice daily.
      Examinations for extrinsic tooth stain were repeated after 2 and 3 weeks. Ninety
      seven subjects complied with the protocol and completed the entire study. At both
      the 2- and 3-week examinations, subjects assigned to the liquid whitening gel
      treatment group exhibited statistically significant reductions in extrinsic tooth
      stain (P < .05) with respect to stain area (22.7% reduction at 3 weeks), stain
      intensity (26.3% reduction at 3 weeks), and overall stain removal (32% reduction
      at 3 weeks) compared with the commercially available whitening dentifrice group.
      Thus, the results of the examiner-blind clinical study support the conclusion
      that Colgate Simply White Clear Whitening Gel provides a significantly greater
      level of extrinsic tooth-stain removal efficacy than a commercially available
      whitening dentifrice.

PMID- 12789994
TI  - Efficacy of a novel, nontray, paint-on 18% carbamide peroxide whitening gel.
AB  - A double-blind, 3-week, randomized, placebo-controlled, parallel-group clinical
      trial was conducted to evaluate the tooth-whitening efficacy of a novel nontray,
      "paint-on" liquid whitening gel containing 18% carbamide peroxide (Colgate Simply
      White Clear Whitening Gel). Efficacy was based on measured Vita tooth-shade
      scores collected at baseline and after 2 and 3 weeks of product use. Eighty
      healthy volunteers were balanced into 2 groups based on gender, age, and shade
      scores (A3 or higher). The duration of product usage was 30 minutes, twice daily,
      for 3 weeks. Results from this clinical study showed that subjects' teeth in the
      liquid whitening gel-treated group exhibited an overall mean 3.84-shade
      improvement and a 3.5-shade difference compared with teeth in the placebo gel
      group (statistically significant, P < .05) after 3 weeks. Furthermore, this
      improvement exceeds the minimum requirement to claim "clinical efficacy" as
      established by the "Guidelines for the Acceptance of Peroxide-Containing Oral
      Hygiene Products," published by the American Dental Association in 1994.
      Therefore, it can be concluded that Colgate Simply White Clear Whitening Gel
      significantly whitens teeth.

PMID- 12789995
TI  - Improving the oral health of Hispanic populations: challenges and opportunities.

PMID- 12789997
TI  - The diabetes-oral health connection.

PMID- 12789996
TI  - Caries management in children: decision-making and therapies.

PMID- 12789998
TI  - Hepatitis C infection: implications for dental care providers and dental care.

PMID- 12789999
TI  - Oral and oral pharyngeal cancer: an update on incidence and epidemiology,
      identification, advances in treatment, and outcomes.
AB  - Dental health care providers offer a primary means by which improvements in
      outcome in oral and oral pharyngeal cancer can be realized. Early detection of
      mucosal abnormalities (e.g., leukoplakia, erythroplakia), which may represent the
      earliest identifiable premalignant change, requires only thorough oral
      examination skills. Patient education and efforts to decrease the use of tobacco
      products are a critical means of decreasing incidence. Changes in cancer
      incidence related to tobacco cessation will take many years to affect statistical
      rates of oral and oral pharyngeal cancer.

PMID- 12790000
TI  - Genetic syndromes of the head and neck associated with cancer: what else to look
      for in the presence of positive orofacial findings.

PMID- 12790001
TI  - Barriers that affect achieving and maintaining oral health among Hispanics.

PMID- 12790002
TI  - Barriers to achieving and maintaining the oral health of Hispanics: working with
      the community to develop a community-based oral health promotion program.

PMID- 12790003
TI  - Children's Dental Safety Net--a collaborative initiative of San Diego County's
      Council of Community Clinics.

PMID- 12790004
TI  - Strategies to build an effective dental hygiene infrastructure for the Hispanic
      community.

PMID- 12790005
TI  - The role of organizational infrastructure in promoting change: lessons from the
      American Dental Education Association.
AB  - Meeting the oral health needs of the Hispanic community can only be accomplished
      with the establishment of an effective infrastructure--one that will attract our
      "best and brightest" candidates and ensure their successful transition into the
      profession. The ADEA is proud of its leadership role in addressing the many
      issues that pertain to this infrastructure, and it is committed to collaborating
      at every level to help meet the oral health needs of the Hispanic population--and
      all underserved populations--in the United States.

PMID- 12790006
TI  - The Pennsylvania Dental Association's initiatives to develop relationships with
      the Hispanic Dental Association.
AB  - All dentists should think seriously about actively participating in their dental
      organizations and becoming a part of the ADA tripartite system. We can bring
      about change, but this will occur only by having strength in numbers. Presently,
      the ADA has a 70% market share of active licensed dentists. We want all national
      dental groups to be a part of this mix so that we can meet the challenges before
      us--and work together to ensure the delivery of the very best dental care to our
      patients.

PMID- 12790007
TI  - Building an effective research infrastructure to meet the oral health needs of
      the Hispanic community.

PMID- 12790008
TI  - A modular approach to dental implant therapy: the appropriate selection of one-
      and two-stage surgeries.
AB  - Different clinical situations merit careful consideration of the surgical and
      restorative approaches taken during the process of tooth replacement using dental
      implants. When clinically feasible, one-stage surgical procedures and subsequent
      restoration offer practical advantages. Modular implant designs comprised of
      separate endosseous implants and transmucosal abutments provide important
      clinical advantages for one-stage surgeries. The biological and mechanical
      advantages of conus implant-abutment interfaces reinforce the selection of
      modular implants for the broad application of one-stage dental implant
      procedures.

PMID- 12790009
TI  - Achieving and maintaining predictable implant esthetics through the maintenance
      of bone around dental implants.
AB  - The position of gingival soft tissues depends on the position and health of the
      underlying alveolar bone. Implant designs are evolving to maintain bone at
      predictable positions on the implant body through the development of stable and
      simplified prosthetic choices in abutment designs. The positioning of the
      restorative abutment deep inside the implant allows the abutment-implant joint to
      remain stable for a prolonged service life. With this stability, the titanium
      abutment allows the connective tissue and junctional epithelial seal ("biological
      width") to form and remain on the side of the abutment, rather than the side of
      the implant. Abutment joint stability plus well-defined implant surface
      topographies allow predictable implant rehabilitation in challenging situations.
      With the use of a mechanically and biologically stable joint interface, the
      prosthetic flexibility of a two-piece modular-style implant system allows the
      greatest flexibility for application in routine surgical and restorative implant
      dentistry.

PMID- 12790010
TI  - Understanding the intimate relationship between biomechanics and optimal clinical
      performance: application of implant design.
AB  - The intimate relationship between living oral tissue and artificial dental
      implant material is complex. Some of the factors that influence clinical outcome
      include the: biological inertness, biocompatibility and/or biotoxicity of the
      implant material; differential elasticity of the materials and tissues; implant
      design; primary implant stability; manner by which the tissues attach to the
      material surface; topography of the material surface; presence of micromovement;
      and implant-abutment joint design (micromovement and microleakage). This article
      presents the fundamental data available on these factors and gives an insight
      into how they affect our understanding of current implant technology.

PMID- 12790012
TI  - Dental caries: risk assessment and treatment solutions for an elderly population.
AB  - Caries remains one of the top three most common infectious diseases in the world
      today. Although caries prevalence decreased markedly in children and in adults up
      to age 40 between 1975 and 2000, the overall risk for caries in older age groups
      (45 to 64, 65 to 84, and > 85 years of age) has not decreased appreciably. In
      fact, the risk for caries in individuals 70 years of age and older has increased.
      The increase in restorative work needed between 1990 and 2030 will be highest in
      adults over the age of 44 years. Root caries prevalence and the number of
      restored teeth will be greatest in the elderly population. Approximately 30% of
      individuals over the age of 65 will have no permanent teeth. It is also apparent
      that additional caries risk factors are associated with a significant proportion
      of the older population, including reduced saliva flow, inadequate oral hygiene,
      frequent sugar intake, Asian ethnicity, and the presence of partial dentures. The
      principles of modern caries management focus on risk assessment, risk reduction,
      monitoring noncavitated carious lesions, and the assignment of specific treatment
      options according to risk. Because a relatively high proportion of elderly
      patients will remain at high risk for caries, therapeutic regimens for managing
      caries as an infectious disease must focus on the use of antibacterial treatment;
      high-fluoride dentifrices; supplementary low-dose, high-frequency fluoride
      rinses; patient education; and shorter recall intervals.

PMID- 12790011
TI  - Aging successfully: oral health for the prime of life.
AB  - Aging is a worldwide phenomena. More adults, particularly those in developed
      countries, are living longer and healthier lives. The average US life expectancy
      was 47 years in 1900; by 2000, it had increased to 74 years. As the population
      ages, the number of adults with acute and chronic illnesses increases. The use of
      medications also increases with age. People over 65 years of age make up about
      12% of the US population, but they consume 30% of all prescription medications,
      many of which can have a negative impact on oral health. Although tooth loss is
      declining in US adults, the need for various types of dental services in the
      adult population continues to increase. Data on the use of dental services has
      shown that dental visits by older adults correlate with the presence of teeth,
      not age. Research on the epidemiology of periodontal disease in older adults
      suggests that the disease in older adults is probably not due to greater
      susceptibility but, instead, the result of cumulative disease progression over
      time. Data on root caries has shown that exposed root surfaces, in combination
      with compromised health status and the use of multiple medications, can increase
      an older adult's risk for root caries. Oral candidiasis commonly occurs in
      immunocompromised individuals of any age, but in older adults, nursing home
      residents are particularly susceptible. Oral cancer is a disease of older adults,
      with a median age of 64 at diagnosis. Tobacco and alcohol use are the most common
      risk factors. Mental or physical impairments, such as dementing illnesses, or
      impaired dexterity as a result of arthritis or stroke, can impair an adult's
      ability to perform adequate oral self-care. Preventing oral diseases in older
      adults requires an understanding of the risk factors for oral diseases and how
      these risk factors change over time. Of particular concern are nursing home
      residents, who remain the most vulnerable of elders. Incorporating preventive
      oral health strategies into dental treatment and nursing home care will play a
      critical role in maintaining oral health for a lifetime. Oral health education of
      family, caregivers, and nursing home staff is essential if oral diseases are to
      be avoided later in life.

PMID- 12790013
TI  - Oral osteoporosis: is there an association between periodontitis and
      osteoporosis?
AB  - Osteoporosis and periodontitis represent two highly prevalent diseases associated
      with advancing age. There is evidence that a patient with systemic osteoporosis
      is likely to have decreased oral bone density, which may affect treatment
      decisions. Further, a patient with decreased bone mineral density, indicative of
      osteoporosis, may be at a higher risk for periodontitis progression. Therefore,
      osteoporosis could be considered a risk factor for periodontitis. Ultimately,
      many of the medical, nutritional, and lifestyle interventions that are beneficial
      in the management of osteoporosis have the potential to be applied to oral health
      care and the management of oral bone loss.

PMID- 12790014
TI  - Distinguishing Mars from Venus: emergence of gender biology differences in oral
      health and systemic disease.
AB  - We are learning to appreciate and understand that men and women have different
      genes and gene products (proteins), biochemistry and physiology, body weights and
      distribution of fats, and a few different tissues and organs. In such
      comparisons, we discover that women have a different prevalence for many oral and
      systemic diseases and disorders, and often illustrate differences in responses to
      disease mechanisms as well as to drug therapy and treatments. For example,
      consider the milestones of development, such as puberty or menopause, the unique
      differences in the prevalence of autoimmune diseases and disorders (Sjogren's
      syndrome, Hashimoto's disease), differences in the onset and progression of
      osteoporosis and osteoarthritis, differences in response to radiation and
      chemotherapy, and the differences in chronic facial pain, chronic fatigue
      syndrome, and fibromyalgia. This article highlights many opportunities to enhance
      the quality of oral health care for women.

PMID- 12790015
TI  - The three phases of Eve: exploring the common and unique findings in oral and
      systemic health of differently aging women.
AB  - Given that, collectively, women are the longer-lived of the human species, it is
      fitting that we examine the impact and correlations of aging on systemic and oral
      health with women as the paradigm. Aging, however, is not a homogeneous process.
      Its influences are as diverse as the subgroups of people affected. To exemplify
      the differing manifestations and progressiveness of aging, this article
      highlights the profiles of three differently aging women: an independent dweller
      in the community, a participant in an assisted living program, and a resident of
      a skilled nursing home. How aging has affected their lives commonly and uniquely
      is addressed, as are medical and oral health issues that transcend functional
      capability, and evolving research in preventive strategies focusing on successful
      aging.

PMID- 12790016
TI  - Dry mouth: aging and oral health.
AB  - Dry mouth is a common complaint among older adults, and the aging process is
      erroneously considered by many to be the primary cause. The subjective complaint
      of dry mouth (xerostomia) is not always associated with objective evidence of a
      reduced saliva flow rate (salivary gland hypofunction). Moreover, there are
      patients who have reduced saliva flow rates and are asymptomatic. Xerostomia and
      salivary gland hypofunction are associated with sundry oral and systemic
      complications and affect the quality of an individual's life. This article
      includes the common causes of xerostomia and salivary gland hypofunction and
      addresses the common complications of and routine therapeutic modalities
      available for these conditions in the elderly.

PMID- 12790017
TI  - Technology integration: a journey, not a destination.
AB  - This article discusses the integration of the latest technologies into the dental
      practice. Given the rapid rate of obsolescence in computer hardware, clinicians
      need to look to practice-management software to build the foundation for
      incorporating all future applications into a smoothly running operation.
      Combined, the core components of the clinical dental record, digital radiography,
      intraoral and digital cameras, and cosmetic imaging create an integrated dental
      image-management system that is becoming a critical factor in how we communicate
      with our patients and with each other.

PMID- 12790018
TI  - Managing and practicing in the dental office: the EagleSoft difference. An
      interview with Mr. Scott Kabbes, president, EagleSoft.

PMID- 12790019
TI  - Transitions to technology: the return on investment.

PMID- 12790021
TI  - [Main results of tuberculosis control in Russia in 2001].

PMID- 12790020
TI  - Hydraulic sinus lift with sinus condensers. Interview.

PMID- 12790022
TI  - [Use of the major components methods in epidemiological studies].
AB  - When multifactorial processes are analyzed, it is most rational to use the
      methods of multidimensional statistical analysis, including the major components
      methods. This method is rather new in epidemiological surveys. Its advantage is
      that it may be used to get information that is difficult derived by other ways.
      Noteworthy is the versatility of the method, which lies in that the problems of
      analysis, prediction, and classification (stratification) of temporal series are
      solved by using actually the same techniques. How to apply the major components
      method are considered by using an example of investigating the general trends in
      the development of an epidemic tuberculous process in a specific area.
      Statistical data on tuberculosis morbidity in the areas of the Novosibirsk Region
      were employed as the initial material.

PMID- 12790023
TI  - [New approaches to timely detection of pulmonary tuberculosis recurrences].
AB  - To improve the organization of timely detection of recurrences of pulmonary
      tuberculosis under the present conditions assumes a differential approach to
      following up the persons recovered from tuberculosis or to observing them in the
      outpatient setting with emphasis on socially defective contingents.

PMID- 12790024
TI  - [Current aspects of tuberculosis infection in children in West Siberia].
AB  - The paper presents the epidemiological features of tuberculosis in children from
      West Siberia at the present stage. It covers the problems of primary its
      contamination and morbidity in children, including those at risk. An algorithm of
      a physician's efforts is proposed depending on the results of the Mantoux test
      with 2 TE (PPD-L) in children. The use of the algorithm is aimed at optimizing
      the joint activities of a pediatric service and a phthisiopediatric one.

PMID- 12790025
TI  - [Diagnostic value of the forced oscillation test in detection of bronchial
      obstruction].
AB  - Clinical testing of the forced oscillation test (FOT) yielded criteria for
      bronchial obstruction: an increase in viscous respiratory resistance (VRR) (Rfo,
      Rin, Rex); the frequency dependence of VRR; and a decrease in a phase angle. The
      study of VRR promoted detection of bronchial malpatency in additional 20.7% of
      the individuals who had no bronchial obstruction, as evidenced by spirography
      (SG) and forced expiration volume-current curve (FEV-CC) recording. To improve
      the diagnosis of bronchial patency impairments, it is expedient to use FOT of VRR
      along with the routine methods (SG and FEV-CC recording). A relationship has been
      established between the values of VRR and the clinical signs of chronic
      bronchitis and the degree of bronchial obstruction.

PMID- 12790026
TI  - [Thermovision diagnosis of tuberculosis of the spine and large joints].
AB  - A comprehensive study was carried out in 95 patients with different forms and
      stages of osteoarticular tuberculosis by using the thermographic diagnostic
      technique. The patients' age was 17 to 76 years. The study was undertaken to
      define the capacities of thermography for differential diagnosis of
      osteoarticular tuberculosis from noninflammatory disease of the skeleton and to
      evaluate the efficiency of treatment in phthisiorthopedic patients. The study has
      provided evidence for that thermography has great capacities to diagnose a
      specific inflammatory skeleton lesion and to evaluate the efficiency of
      treatment, which allows one not to carry out expensive and radiation load
      carrying X-ray studies in some cases.

PMID- 12790027
TI  - [Optimization of the detection, diagnosis, and prevention of advanced forms of
      pulmonary tuberculosis].
AB  - A rise in the number of patients with disseminated and advanced forms of
      tuberculosis becomes a great problem in phthisiology. The quality of tuberculosis
      control depends on the organization of examination of patients with the suspected
      tuberculosis etiology of the disease. Thus, the authors propose to optimize both
      general and addressing tuberculosis controlling measures, which include among
      them to improve general practitioners' qualification as the latter largely
      determines the efficiency and timeliness of verification of a tuberculous
      process.

PMID- 12790028
TI  - [On early transfer of new cases of pulmonary tuberculosis to outpatient
      treatment].
AB  - Based on 228 clinical cases, the authors propose procedures for complex two-stage
      (inpatient and outpatient) treatments of new cases of pulmonary tuberculosis by
      using intermittent intravenous chemotherapy that makes it possible to have a high
      therapeutic effect in a short space of time, to reduce the duration of hospital
      treatment substantially, to on the average 2-4 months, and to ensure controlled
      chemotherapy at the outpatient stage.

PMID- 12790029
TI  - [Modalities of complex therapy in different categories of patients with pulmonary
      tuberculosis].
AB  - The paper proposes the standards of combined treatment involving intermittent
      intravenous bactericidal chemotherapy for different groups of patients. It
      describes treatment regimens at the inpatient stage, defines the scope and time
      of control examination and correction of a treatment protocol by taking into
      account the pattern, phase, and dissemination of a process and the duration of
      the disease.

PMID- 12790030
TI  - [Tuberculosis of the central nervous system in preschool children].
AB  - The clinical and X-ray forms of tuberculosis were studied in 1481 patients aged
      under 7 years who had been treated from 1970 to 2000. Patients with tuberculosis
      of the central nervous system accounted for 5.5%. In the past 15 years, there was
      an increase in the share of generalized tuberculosis, more severity of the
      clinical course of tuberculous meningitis, and a rise in the incidence of deaths
      from the disease. Children of the first year of life fell ill more frequently.
      The main causes should be considered to be exogenous superinfection whose role
      increases under the conditions of an undetected reservoir of tuberculous
      infection; no biomedical protection as tuberculosis controlling measures; no
      protection of children from socially disadapted families. A fatal case was
      recorded in half the patients. The other half was discharged as having rough
      residual changes in the central nervous system.

PMID- 12790031
TI  - [Treatment of patients with destructive pulmonary tuberculosis and nonspecific
      purulent endobronchitis].
AB  - Imozymase treatment should be started from the first hospital days in patients
      with destructive pulmonary tuberculosis concurrent with nonspecific purulent
      endobronchitis. Two-week ultrasound inhalations with imozymase in a dose of 1 ml
      (60 PU) may rapidly abolish not only the nonspecific inflammatory bronchial
      process, but also accelerate the attenuation of symptoms of intoxication, the
      time of abacillation, cavernous closure, and preparation for surgical
      interventions.

PMID- 12790032
TI  - [Role of surgical treatments in patients with fibrocavernous pulmonary
      tuberculosis].
AB  - Three hundred and seventy patients operated on at the Institute Surgical Clinic
      underwent 638 surgical interventions: 356 and 282 in Groups 1 and 2 patients,
      respectively. Intraoperative complications occurred in 24 (3.8%) cases, in 6.5%
      of the patients operated on. Twenty-two complications were successfully
      eliminated, 2 patients died. Postoperative complications were established in 25
      (14.8%) of the 169 patients of Group 1 and in 12 (6.0%) of the 201 patients of
      Group 2. The incidence of complications largely depended on the type of an
      operation. Complications were observed in 8 (36.4%) of the 22 patients undergone
      pulmonectomy. The active phase of a specific process as a surgical risk factor is
      prime consideration. In patients operated for emergency indications in the phase
      of an non-arrested exacerbation of tuberculosis, pleuropulmonary complications
      occur 2.5 times as frequently as those in patients with relative process
      stabilization.

PMID- 12790033
TI  - [Osteoplastic thoracoplasty with concomitant pulmonectomy in the surgery of
      generalized destructive pulmonary tuberculosis].
AB  - The paper analyzes the results of surgical treatment in 155 patients with
      generalized destructive pulmonary tuberculosis who underwent pulmonectomy
      concomitantly with different types of thoracoplasties in 1986 to 1999. According
      to the type of thoracoplasty, all the patients were divided in 3 groups: 1) 38
      patients undergone pulmonectomy with concomitant osteoplastic thoracoplasty; 2)
      41 patients had pulmonectomy with concomitant extrapleural thoracoplasty; and 3)
      76 had pulmonectomy with concomitant intrapleural thoracoplasty. On discharge,
      the full clinical effect was achieved in 92.2% of the patients from Group 1 with
      their mortality rates of 2.6, whereas in the control groups (Groups 2 and 3), the
      efficiency of treatment was less and the mortality rates were higher (82.9 and
      4.9% in Group 2 and 76.3% and 3.9% in Group 3, respectively). Long-term results
      in 132 patients were followed up for 2-15 years. Clinical recovery was stated in
      91.2, 77.8, and 83.3% in Groups 1, 2, and 3, respectively.

PMID- 12790034
TI  - [Clinical and morphological comparisons in pulmonary tuberculosis in workers from
      pneumoconiosis-risk industries].
AB  - The relationship between the efficiency of treatment and the nature of
      morphological changes in the lung was studied in 125 patients with pulmonary
      tuberculosis without X-ray signs of pneumoconiosis who worked at coniosis-risk
      enterprises (CRR). Despite adequate specific and pathogenetic therapy,
      tuberculomas formed and decay cavities preserved in the patients, in this
      connection they had surgical treatment. Three types of morphological changes were
      identified. Quartz-containing industrial dust was found to exert an adverse
      potentiating effect on the course of tuberculosis in most CRE patients: increases
      in the delimiting a specific process of respiratory disorders and postoperative
      complications. These specific features should be borne in mind in drawing up a
      treatment protocol for patients working exposed to industrial dust.

PMID- 12790035
TI  - [Molecular genetics of Mycobacterium tuberculosis].

PMID- 12790036
TI  - [Differential diagnosis of tuberculosis of the urinary system].

PMID- 12790038
TI  - [Use of artificial pneumothorax and pneumoperitoneum in the treatment of
      destructive pulmonary tuberculosis under present conditions].

PMID- 12790037
TI  - [New organizational forms of antituberculosis care under present conditions.
      Results and experience exchange of work in pilot regions. Scientific-and
      Practical Conference (Moscow, September 25-27, 2002)].

PMID- 12790039
TI  - [Electron paramagnetic resonance in the diagnosis of pulmonary tuberculosis
      activity].

PMID- 12790040
TI  - Prologue: ventricular assist devices and total artificial hearts. A historical
      perspective.
AB  - In the 1960s, when LVADs and TAHs were introduced into clinical use, researchers
      estimated that, with this technology, the problem of heart failure could be
      solved within 20 years. Unfortunately, the evolution of these devices has taken
      much longer than anticipated. Nevertheless, significant advances have been
      achieved in both cardiac assistance and replacement, and today's cardiac surgeons
      have a wide range of devices from which to choose (Table 4). This progress has
      largely been due to the support of the NHLBI, especially the Devices and
      Technology Division headed by John Watson, and of the devoted commitment of the
      investigators. Because of the long-term commitment required for both basic and
      clinical research, commercial medical technology companies are unable to assume
      this burden. Advances in mechanical circulatory support and replacement have
      benefited numerous patients worldwide who would otherwise have died of heart
      failure, and devices now exist for use as bridges to recovery, bridges to
      transplant, and destination therapy. The current challenge is to refine what we
      have and to apply these technologies to broader patient populations with maximal
      safety and at a reasonable cost.

PMID- 12790041
TI  - Physiologic and hemodynamic basis of ventricular assist devices.
AB  - Heart failure is a particularly complex disorder with etiology that is primary in
      nature or secondary to other systemic diseases, including hypertension, diabetes,
      and atherosclerosis. The pathogenesis appears to result, in part, from extensive
      abnormal interactions among tissues, such as the heart, vasculature, kidney,
      lungs, and sympathetic nervous system. Improvements in understanding this complex
      disorder, particularly factors that contribute to cardiac cell cycle alterations,
      gene activation and re-expression resulting in cardiac remodeling and,
      eventually, maladaption are paramount. Clinical experience with the current
      generation of mechanical blood pumps continues to be promising; nonetheless,
      these devices are not the definitive therapy for all patients with heart failure.
      The next generation of devices capable of mimicking many of the native heart pump
      attributes, such as responsiveness to preload, afterload, contractility, and beat
      rate, will broaden the use of this technology. In addition to solving the
      fundamental engineering challenges (size, energy supply, biocompatibility,
      durability, and portability), implantable heart pumps that are physiologically
      adaptive would enhance the treatment strategies for prolonged chronic support.
      The ultimate measure of device mediated success is to show improvements that
      extend beyond a favorable hemodynamic profile and include nutritional status and
      metabolic and neurohormonal levels and must demonstrate improved exercise
      tolerance and a better quality of life.

PMID- 12790042
TI  - Extracorporeal mechanical circulatory assist.
AB  - There are currently several safe and effective options to provide temporary MCS
      for patients presenting with cardiogenic shock or refractory heart failure. Newer
      device designs are currently being developed that will increase the options
      available to patients. Due to the technological advancements, it will be
      difficult to predict what devices will ultimately prove to be the most
      efficacious. It is likely that a variety of devices will be necessary, depending
      on clinical circumstances and patient characteristics.

PMID- 12790043
TI  - Management of acute cardiogenic shock.
AB  - The present state of the art in mechanical cardiac assist technology has
      permitted application of machines to a variety of conditions that confound the
      cardiologist and cardiac surgeon alike. Decades of research and development have
      allowed the present devices to be used as bridges to native heart recovery and
      bridges to transplantation. We are now entering the era in which devices are
      being placed for permanent assist or replacement. Although the acute cardiogenic
      shock patient remains problematic, we now have at our disposable a variety of
      tools that have enabled us to salvage more patients than ever before. The
      experience with these systems continues to grow, with leading centers and
      investigators contributing meaningful information toward the application and
      development of the latest technologies. It has been said that mechanical
      therapies precede biological therapies. We are at the crossroads in which a
      combination of biological therapies with mechanical therapies is underway.
      Current research is investigating the role of mechanical cardiac support while
      biological therapies are introduced into the failing heart. In the meantime, the
      role of mechanical cardiac assist and replacement has matured into an effective
      means of treating acute cardiogenic shock of any variety.

PMID- 12790044
TI  - Indications for long-term assist device placement as bridge to transplantation.
AB  - The current indications for long-term mechanical support as bridge to
      transplantation first require the patient to be a transplant candidate. Often
      times a patient presents with limited history and refractory cardiogenic shock,
      where a full transplant work-up for contraindications cannot be safely performed.
      The use of short-term mechanical support can be used to help filter out many
      patients who have easily identifiable contraindications to heart transplant.
      Nevertheless, patients need to be listed for a heart transplant before the
      implantation of some of these devices. This paradigm needs to be altered, because
      there are many instances where mechanical support can be used to support a
      patient for an intervention to "make" them a transplant candidate where they
      otherwise would not have been. Long-term mechanical support can overcome the
      cardiac contraindication to the surgical/interventional therapy to "cure" them of
      the process that would have prevented them from being a good cardiac transplant
      candidate in the first place. Noncardiac surgical procedures are well tolerated
      in these patients [11]. The FDA is currently evaluating the Vented Electric
      Heartmate system for use as destination therapy for patients who are not
      transplant candidates. Approval for this indication (with a device that is
      already approved for bridge to transplantation) will allow this paradigm shift.
      This system could be used in the group who may be good candidates, but not
      determined. If they were subsequently determined to not be a good surgical
      candidate, they would be chronically supported with the LVAD as destination
      therapy.

PMID- 12790045
TI  - Long-term implantable left ventricular assist devices: out-of-hospital program.
AB  - The assist devices demonstrate the safety and reliability of these systems in the
      management of end-stage cardiac failure, not only in an in-hospital setting, but
      also in the cohort of OOH patients. The OOH option has led to a significant
      improvement in the quality of life of those patients. However, VADs are still
      associated with a considerable number of complications. The newly introduced
      fully implantable system (LionHeart) has reduced significantly the system-related
      infection complications. Further miniaturization of the systems might reduce the
      comorbidities and increase the acceptance of this therapeutic option in the
      management of end-stage cardiac failure.

PMID- 12790046
TI  - Devices as destination therapy.
AB  - The use of circulatory support as destination therapy has been a goal for the
      treatment of endstage heart failure for several decades. Current investigations
      are evaluating several circulatory pumps with that particular objective. With
      continued modification of design, the current and future pumps will become more
      reliable and provide improved quality of life to patients in need of mechanical
      circulatory assistance. The new pumps on the horizon specifically address
      reliability, size, and cost, and are based on the centrifugal system. These
      devices use the Maglev (Magnetic Levitation) concept that allows for frictionless
      pumping, low thrombogenicity, minimal noise, and increased durability. Further
      research with this goal in mind and support from the federal government will be
      the key to the future use of circulatory assistance as destination therapy for
      heart failure patients. In addition, the cost-effectiveness of these devices will
      need to be maintained as the technology improves, as in any new technology that
      confronts a more intuitive option like the native heart.

PMID- 12790047
TI  - Pathogenetic basis of myocardial dysfunction and amenability to reversal.
AB  - As the role of the LVAD graduates from the "bridge-to-transplant" to the "bridge
      to-recovery," several important issues need to be answered. Such a paradigm would
      require a definition of appropriate candidates for LVAD implantation, the most
      appropriate time for LVAD placement during the management of end-stage CHF,
      reliable histologic, biochemical, and imaging markers of recovery, and the
      optimum duration of LVAD support. The device technology must be refined further
      to reduce the morbidity associated with the device itself, and to make the device
      smaller, less invasive, and less thrombogenic. It will be a challenge to identify
      the role for concomitant drug therapy and to develop weaning programs for device
      support. Finally, guidelines will have to be developed to monitor and manage
      these patients after explantation of LVAD.

PMID- 12790048
TI  - Outpatient management of long-term assist devices.
AB  - Current VAD technology has enabled patients to be safely discharged from
      hospital, awaiting transplantation in the setting of their home. The results of
      recent studies have proven that patients on LVADs as destination therapy fare
      better than their medical counterparts and enjoy a higher quality of life. The
      lessons learned thus far in the outpatient management of LVADs has convinced the
      medical and non-medical communities that this form of therapy is more than
      feasible in addressing the epidemic of heart failure. Newer devices are on the
      horizon. It is inevitable that more patients will be visible in the streets and
      workplace as the modifications in size and application become more user friendly.
      It will be our responsibility, as the guardians of this technology, to use it
      wisely and provide the support that is necessary for this special population of
      people.

PMID- 12790049
TI  - Total artificial hearts: bridge to transplantation.
AB  - The CardioWest TAH was created and initially tested at the same time as the
      Thoratec, Novacor, and HeartMate devices. It was designed as a permanent
      artificial heart and was the first-ever mechanical circulatory device to be used
      as destination therapy. Twenty years have passed since that early experience.
      Pneumatic technology is still current and being developed as in existing or new
      implantable Thoratec VADs the pneumatic HeartMate, and the Abiomed BVS 5000
      pumps. Portable pneumatic drivers have been available since 1982, and in recent
      times have allowed discharge to home of substantial numbers of patients, thus
      reducing the length of hospital stays and making mechanical device support less
      expensive to society and more tolerable to patients. Within months, a portable
      driver for the CardioWest will be available. The documented benefits of the
      CardioWest TAH include rescue of: critically ill patients with advanced heart
      failure; patients with biventricular failure especially those with significant
      right heart failure, elevated pulmonary vascular resistance, or pulmonary edema;
      patients with renal or hepatic failure secondary to low cardiac output; patients
      with massive myocardial damage such as those with post-?infarction VSD or
      irreversible cardiac graft rejection; patients with mechanical valves or native
      valve disease; and patients with intractable arrhythmias and heart failure. High
      device outputs with restoration of normal filling pressures result in high
      perfusion pressures that have led to dramatic recoveries, convalescence, and
      return to levels of activity compatible with normal life. The average device
      output with the CardioWest TAH is higher than any other approved or
      investigational device. The reason for this resides in design simplicity this
      device has the shortest and largest inflow pathway. Stroke, in the authors' own
      series, is rare with a linearized rate of 0.068 events per patient year. If the
      experiences of La Pitie and the University of Arizona are combined, there has
      been one stroke in 25 patient years (0.04 events/patient year). Serious
      infections have been rare (12% of patients). No clinical mediastinitis has
      occurred. Drivelines have healed in tightly and never caused an "ascending"
      infection. There has not been a case of device endocarditis. Using a broad
      definition of bleeding, including takeback reoperation for bleeding, bleeding
      more than 8 units in the first postoperative 24 hours or 5 units over any other
      48-hour period, a 25% to 36% incidence has been documented. No cases of fatal
      exsanguination have resulted, as there have been with the HeartMate. The
      incidence of bleeding as an adverse event is about 17% lower than the rate
      reported for the HeartMate VE LVAD, and it is about the same as that reported for
      Novacor and for Thoratec. Implantation of this device is relatively easy and
      often done (with attending help) by the authors' residents. If one follows the
      guidelines for fitting the device, and takes the recommended advice for
      implantation, hemostasis is excellent and restoration of immediate cardiac
      function with high flows is nearly automatic. Use of a neopericardium of 0.1 mm
      EPTFE at the time of implantation assures atraumatic and relatively quick re
      entry for transplantation and prevents the normal inflammatory mediastinal
      reaction that might be desirable in a destination application. In selected
      patients the CardioWest TAH is the device of choice for bridge to
      transplantation. When a portable driver becomes available, out of hospital
      management of CardioWest TAH patients will be feasible and consideration of use
      of this device for longer term applications, (e.g., "destination therapy,") will
      be reasonable. A wearable driver, even smaller than a portable, will improve
      quality of life and expand the patient population that may be therapeutically
      served with this system. In short, the CardioWest TAH has come nearly full
      circle. It was first used as a destination device. It has since been used as a
      bridge to transplantation in nearly 200 patients as the Jarvik-7/Symbion TAH and,
      since 1993, in over 225 patients as CardioWest. The results have improved with
      time. Thromboembolism and infection rates have been competitive with currently
      available devices. Device reliability and durability have been excellent.
      Survival rates have been very high in a group of perhaps the sickest patients to
      be supported with any pulsatile device. Pneumatic technology has improved with
      portability and miniaturization, and there is reason to believe that it will
      become even better. Application of modern manufacturing techniques to this very
      simple device raises the possibility of significant manufacturing cost reduction,
      in an era of prohibitive cost for other devices. All of this establishes the
      CardioWest as a valuable device for any program that is seriously interested in
      end-stage heart disease and a likely device for permanent use in appropriately
      selected patients.

PMID- 12790050
TI  - Total artificial heart: destination therapy.
AB  - The AbioCor is a revolutionary device. It is the only device of its kind in the
      clinical world. The role of the AbioCor is to provide permanent replacement of
      the failing heart for patients who are not transplant candidates. The clinical
      trial has been successful in the majority (four of seven) of patients implanted
      thus far. Eight more patients are required to complete the initial feasibility
      phase of the trial, afterwhich it remains to be seen if the trial will expand to
      additional patient populations. The powerful features of the pump have been
      demonstrated in the extremely sick group of candidates that enrolled in the
      study. The TET system has worked extremely well. Lastly, the milestone of
      discharging a patient to home on a completely internal artificial heart has been
      realized. The profile of CardioWest is very different from AbioCor. Although both
      were initially designed as permanent replacement therapies, the CardioWest has
      been extremely useful as a bridging device, and it may have a broader application
      in the future. For the CardioWest, the most favorable groups are patients with
      cardiomyopathy who decompensate while awaiting transplantation. On the other
      hand, the AbioCor is indicated in nontransplant candidates with biventricular
      failure who have a less than 30-day predicted survival. Proper patient selection
      is critical to achieving success with either device.

PMID- 12790051
TI  - Immunobiologic consequences of assist devices.
AB  - The aberrant state of monocyte and T-cell activation resulting from these host
      device interaction is accompanied by two parallel processes: (1) selective loss
      of Th1 cytokine-producing CD4 T cells through activation-induced cell death, and
      (2) unopposed activation of Th2 cytokine-producing CD4 T cells resulting in B
      cell hyperreactivity and dysregulated immunoglobulin synthesis via Th2 cytokines
      and heightened CD40 ligand-CD40 interactions. The net result of these events is
      that on one hand the VAD recipient develops progressive defects in cellular
      immunity and is at increased risk of serious infection, and on the other hand the
      VAD recipient is more likely to develop allosensitization, posing a significant
      risk to successful transplant outcome.

PMID- 12790052
TI  - Epilogue: support devices for end stage heart failure.
AB  - The present approach to circulatory assist/replacement devices is to use them as
      rescue for a patient in shock while awaiting transplant. In the next decade, the
      paradigm will shift to a more widespread use of such devices in patients without
      subsequent transplantation. Achievement of the ultimate goals of improved
      survival and quality of life for patients with advanced heart disease may depend
      on the strategic use of support devices more frequently than on the total
      replacement heart.

PMID- 12790053
TI  - On food as a recreational drug.

PMID- 12790054
TI  - Enhancing the perceived health of HIV seropositive men.
AB  - The purpose of this study was to examine the relationships between hope, social
      support, uncertainty in illness, and spirituality and their effect on the
      perceived health of HIV seropositive men. A prospective design was used to test a
      causal model on a sample of 125 HIV seropositive men recruited from urban
      HIV/AIDS outpatient clinics. A goodness of fit index of .90 and a comparative fit
      index of .79 indicated minimal fit of the theorized model with the data. Findings
      revealed significant, positive paths from hope to perceived health and from
      spirituality to hope. Significant negative paths were found between social
      support and uncertainty in illness and uncertainty in illness and hope. The level
      of hope may play an important role in enhancing health of HIV seropositive men.

PMID- 12790055
TI  - Ethnicity and prenatal health promotion content.
AB  - Prenatal care health promotion education is an important strategy for reducing
      perinatal health disparities. The purposes of this study were to (a) identify
      differences between the health promotion content women wanted to discuss and the
      content women reported discussing and (b) determine whether ethnicity was related
      to health promotion content. A cross-sectional study used face-to-face interviews
      to obtain data about 159 Mexican American and African American pregnant women's
      prenatal experience. Women wanted more health promotion content than they
      discussed. Despite wanting information about more health promotion topics than
      African American women. Mexican American women discussed fewer topics. Ethnicity,
      number of topics women wanted to discuss, whether a woman had a primary provider,
      and type of prenatal provider model were also related to content.

PMID- 12790056
TI  - Dieting, perceived deprivation, and preoccupation with food.
AB  - A prospective study using 14-day food diaries was conducted to determine whether
      perceived deprivation and preoccupation with food correspond to actual caloric
      and fat intake, using a sample of 121 adult women who were binge eating without
      purging or were currently dieting. Caloric and fat intake were not significantly
      related to perceived deprivation. Only weight cycling and Revised Restraint Scale
      was significantly correlated with perceived deprivation with 11% of the variation
      explained by the Revised Restraint Scale scores. These findings support the
      contention that psychological deprivation occurs regardless of caloric intake.
      For preoccupation with food, only fat intake and Revised Restraint Scale scores
      were significantly correlated with 15% of the variance explained by the Revised
      Restraint Scale scores.

PMID- 12790057
TI  - A qualitative investigation of fatigue among healthy working adults.
AB  - Despite considerable attention to fatigue in acute and chronic illnesses, little
      is known about fatigue in a healthy population. A detailed exploration of
      fatigue, therefore, was conducted to answer the broad question of what fatigue is
      to a basically healthy population and to lay the groundwork for establishing an
      empirically based definition of fatigue. Qualitative and quantitative methods
      were used. Results of the qualitative phase of the study, in which 40 persons
      were interviewed, are presented here. Categories and themes of the experience of
      fatigue were identified. Based on the qualitative findings, we propose that
      fatigue in generally healthy adults is an acute, subjective, sometimes
      overwhelming, but temporary state (with physical, emotional, and behavioral
      manifestations) caused by stress and overwork in one's life roles, which disrupts
      activity and alerts the person to take restorative measures.

PMID- 12790058
TI  - Magnet hospital nurses describe control over nursing practice.
AB  - Staff nurses describe control over nursing practice (C/NP) as a professional
      nursing function made up of a variety of activities and outcomes. Greater
      acclaim, status, and prestige for nursing in the organization are viewed as a
      result, not a precursor, of C/NP. Interviews with 279 staff nurses working in 14
      magnet hospitals indicated that effective C/NP requires some kind of empowered,
      formal organizational structure, extends beyond clinical decision making at the
      patient care interface, and is the same as or highly similar to what the
      literature describes as professional autonomy. From constant comparative analysis
      of nurses' descriptions of C/NP activities, five ranked categories of this real
      life event emerged. The basis for the categories and ranking was "who owned the
      problem, issue, and solution" and the "degree of effectiveness of control" as
      reflected in visibility, viability, and recognition of a formal structure
      allowing and encouraging nurses' control over practice. Hospital mergers and
      structural reorganization were reported to negatively affect the structure needed
      for effective C/NP. Almost 60% of these magnet hospital staff nurses stated
      and/or described little or no C/NP.

PMID- 12790059
TI  - Helping to manage the high cost of rare diseases.
AB  - The recent innovations in electronic technology, discoveries in biotechnology
      research and changes in FDA policy have resulted in the fast-growing market of
      specialty pharmaceuticals. These drug agents offer treatment (where there was
      often none) for patients with rare, chronic diseases such as pulmonary
      hypertension, Gaucher disease, hemophilia and others. The new drug therapies are
      expensive, with an annual average cost of $71,000 a year, and often require
      specialized handling and administration. In response to market need, a new
      service sector called specialty pharmacy has emerged to manage these therapies.
      The specialty pharmacy provides services for specialized drug delivery and
      handling, patient education, drug administration, treatment oversight, and
      reimbursement assistance. These services assist healthcare providers and payors
      to enhance quality care and reduce the administrative burden of managing
      treatments for patients with rare disease.

PMID- 12790060
TI  - Developing a management plan.
AB  - Many complex issues are associated with specialty pharmaceuticals in the
      development of a successful specialty pharmaceutical program. A previous article
      focused on the definition and scope of specialty pharmaceuticals. This article
      explores the mechanics of developing and managing a specialty pharmaceutical
      program, specifically, authorization management.

PMID- 12790061
TI  - Primary care satisfaction among adults with physical disabilities: the role of
      patient-provider communication.
AB  - OBJECTIVES: To determine overall satisfaction with primary care among people with
      cerebral palsy, multiple sclerosis, and spinal cord injury, and to identify
      potential differences in primary care satisfaction between managed care (MC) and
      fee-for-service (FFS) enrollees with these physical disabilities. PARTICIPANTS:
      The sample consisted of 195 people with cerebral palsy (CP), multiple sclerosis
      (MS), and spinal cord injury (SCI), between the ages of 18 and 65 who had
      received primary care services in the six months prior to the survey.
      MEASUREMENTS: Satisfaction with various aspects of primary care were assessed
      using a 10-item self-report measure. Respondents were compared with regard to
      service satisfaction based on disability and insurance type (MC vs. FFS).
      Satisfaction items were summed up to produce an unweighted index of overall
      satisfaction. In the analysis we used non-parametric statistics, such as Kruskal
      Wallis One Way ANOVA and Mann-Whitney Rank tests. Post hoc alpha corrections were
      performed using the Holms Stepdown Procedure. CONCLUSIONS: The lack of disability
      specific knowledge among primary care providers is consistent with findings of
      other studies. People with physical disabilities in managed care plans are less
      satisfied with how their providers communicate with them, relative to those in
      FFS plans. Poor patient-provider communication may place individuals with certain
      physical disabilities at risk for not receiving appropriate care.

PMID- 12790062
TI  - The arrival of consumer-centric healthcare.
AB  - Rising employer healthcare costs are driving the need for new cost-saving benefit
      programs. Consumer-driven health plans have the potential to create savings for
      employers and better care options for patients. Furthermore, three fundamental
      forces need to come together for these health plans to become a reality. First,
      employees need to view healthcare benefits as assets and be provided with the
      tools to manage those assets. Second, employees must have continuity in the
      management of their healthcare assets, which includes their medical utilization
      history. Finally, any savings accumulated in these plans must be employee owned
      and portable from job to job or available for retirement healthcare needs. Making
      consumers active participants in the next generation of health plans is a
      necessity. Making it happen, however, will be a challenge.

PMID- 12790063
TI  - The salience of choice for Medicare beneficiaries.
AB  - The MedicareChoice program was created to expand choice and encourage
      beneficiaries to more actively consider the choices they have. This article
      assesses how "salient" choice is to Medicare beneficiaries. More than half of all
      Medicare beneficiaries in 2000 reported that they either have never considered
      their options to join a Medicare HMO or get supplemental coverage (44 percent) or
      did so last when they first became Medicare eligible (14 percent). Overall, 14
      percent of Medicare beneficiaries found choice salient in 2000. Those new to
      Medicare or forced to switch because their plan left the program were more likely
      to consider choice, as expected. The multi-variate analysis shows that existing
      HMO enrollment is most strongly associated with salience of choice and also that
      this effect operates especially in the individual market. The findings of this
      research are consistent with the literature in highlighting the limited salience
      of choice to Medicare beneficiaries and the even more limited extent of actual
      switching that occurs in that market. There is little reason to believe that
      choice is more salient now than when the study was done. Policymakers who seek to
      encourage market-based solutions confront a dilemma: How to create incentives for
      a choice that most beneficiaries do not find particularly salient.

PMID- 12790064
TI  - Reducing pain and costs with innovative postoperative pain management.
AB  - Individual patient responses to some of the standard-of-care treatments for post
      operative pain management are unpredictable, but studies have shown
      undertreatment of acute post operative pain is common. There are new, innovative
      techniques for postoperative pain management that may improve a patients'
      recovery period. These techniques are also economically beneficial, and may
      contribute to the reduction of long-term care costs. Overall, the less time a
      patient is removed from normal day-to-day activity, the more satisfied they tend
      to be with their surgical experience. The following article addresses these and
      other issues surrounding the reduction of pain and cost after surgery.

PMID- 12790065
TI  - Stealth law: HIPAA's back-door regulation of "business associates".
AB  - The final HIPAA privacy modifications have substantially lightened the
      administrative, compliance, and liability loads borne by health plan and provider
      covered entities. Unlike under the original Clinton rules, for example, covered
      entities are no longer required to obtain patient consents, to monitor and
      mitigate the information practices of their business associates, or to treat
      patients as third-party beneficiaries of their business associate contracts. But
      the final modifications have done almost nothing to lessen the huge burdens and
      expense that will soon be imposed on those managed care entities that are merely
      business associates, a category that Congress never authorized HHS to regulate.

PMID- 12790066
TI  - A test of the California competency-based differentiated role model.
AB  - To address the incongruence between the expectations of nursing service and
      education in California, the Education Industry Interface Task Force of the
      California Strategic Planning Committee for Nursing developed descriptions to
      assist employers and educators in clearly differentiating practice and
      educational competencies. The completion of the Competency-Based Role
      Differentiation Model resulted in the need to test the model for its utility in
      the service setting, in education, and for career planning for nurses. Three
      alpha demonstration sites were selected based on representative geographical
      regions of California. The sites were composed of tri-partnerships consisting of
      a medical center, an associate degree in nursing program, and a baccalaureate
      nursing program. Observers rated senior students and new graduates in medical
      surgical units on their behaviors in teacher and leadership care provider and
      care coordinator roles. The alpha demonstration study results were as expected.
      That is, senior students practice predominantly at a novice level in teacher and
      management/leadership care provider functions and new graduates practice
      predominately at the competent level. New graduates are more likely to take on
      novice and competent care coordinator roles. The CBRDM may be useful for practice
      and education settings to evaluate student and nurse performance, to define role
      expectations, and to identify the preparation necessary for the roles. It is
      useful for all of nursing as it continues to define its levels of practice and
      their relationship to on-the-job performance, curriculum development, and carrier
      planning.

PMID- 12790067
TI  - Restoring members' confidence through plain English.

PMID- 12790068
TI  - The business imperative behind a sound ethics program.

PMID- 12790069
TI  - The US healthcare system--a diagnosis.

PMID- 12790070
TI  - Consumer choice and tiered networks--two sides of the same coin?

PMID- 12790071
TI  - Legal perspectives from Sidley Austin Brown & Wood LLP memo from investors: we're
      watching the cost of complying with HIPAA.

PMID- 12790072
TI  - [Infectious endocarditis: morbi-mortality in Chile. Results of the National
      Cooperative Study of Infective Endocarditis (1998-2002)].
AB  - BACKGROUND: Infective endocarditis is a severe condition, with a mortality that
      fluctuates between 16 and 25% in the Metropolitan area of Chile. AIM: To perform
      a prospective assessment of clinical and microbiological features of patients
      with infective endocarditis in Chile. MATERIAL AND METHODS: Collaborative study
      of regional hospitals in the whole country and teaching hospitals in Santiago.
      Patients with a possible or definitive infective endocarditis, according to
      Duke's criteria, were included in the protocol and a structured data entry form
      was completed. RESULTS: Three hundred twenty one patients (65% male, mean age 49
      +/- 16.5 years) were studied. According Duke's criteria, 89% had a definitive and
      11% a possible endocarditis. The subacute form occurred in 64% of patients. The
      most frequent predisposing cardiopathies were rheumatic in 25%, prosthetic valves
      in 15% and congenital in 13%. There was no evidence of cardiopathy in 20%. Twenty
      percent of patients were on hemodialysis, 11% were diabetic and only one patient
      abused intravenous drugs. The most frequent complication was cardiac failure in
      59% of cases, followed by renal failure in 32% and embolism in 28%. The most
      frequent causing organism was coagulase positive Staphylococcus in 35%. Blood
      cultures were negative in 28% of cases from the metropolitan region, in 56% of
      cases from the north and 38% of cases from the south. Echocardiographic diagnosis
      was done in 92% of cases. Aortic valve was involved in 42% and mitral valve in
      29%. Successful antimicrobial treatment was achieved in 59% of patients. Thirty
      five percent of patients were subjected to surgical procedures with a 78%
      survival. Overall mortality was 29%. Univariate analysis identified sepsis, an
      age over 60 years and the presence of cardiac or renal failure as prognostic
      indicators of mortality. On multivariate analysis, the identified prognostic
      indicators were the presence of sepsis, renal failure, mitroaortic involvement
      associated to combined surgery and failure of antimicrobial treatment not
      associated to surgery. CONCLUSIONS: Subacute form is the most common presentation
      of infective endocarditis and rheumatic valve disease is the most common
      underlying cardiac lesion. Intravenous drugs users infective endocarditis is
      exceptional in Chile. The most frequent causing agent is coagulase positive
      Staphylococcus and the most frequent complication is cardiac failure. Surgical
      and overall mortality were 22 and 29% respectively. Sepsis, renal failure,
      combined surgical procedures, failure of medical treatment were identified as
      prognostic indicators of mortality.

PMID- 12790073
TI  - [Newborn hydronephrosis: dynamic renal scintigraphy with Tc99m MAG3 in the first
      month of life].
AB  - BACKGROUND: The early and accurate diagnosis of obstructive uropathy in the
      newborn, prevents secondary complications and kidney damage. AIM: To study the
      usefulness of Tc99M MAG3 diuretic renogram in newborns with hydronephrosis.
      MATERIAL AND METHODS: Forty newborns, aged 1 to 30 days, with hydronephrosis,
      were studied. A Tc99M MAG3 diuretic renogram (DR) was done and its results were
      compared with clinical features and other imaging studies. Each kidney and its
      ureter, were considered a renal unit. RESULTS: Seventy six renal units were
      evaluated. Twenty six were normal on prenatal ultrasound examination and DR. In
      11 of the 50 renal units with hydronephrosis, renal function was impaired. Thus,
      it was impossible to obtain an excretory curve. In 17 of the 39 remaining renal
      units, the absence of obstructive uropathy was demonstrated clinically. In 16 of
      these, the DR showed absence of obstruction. In 20 of 21 renal units with
      confirmed obstructive uropathy, DR showed an obstructive pattern. CONCLUSIONS: In
      newborns, there is an adequate Tc99M MAG3 uptake and diuretic response. Thus, DR
      becomes a good functional assessment method in newborns with hydronephrosis.

PMID- 12790074
TI  - [Insulin resistance and other expressions of metabolic syndrome in obese Chilean
      children].
AB  - BACKGROUND: Infantile obesity is a probable risk factor for the early appearance
      of chronic illnesses like Type 2 Diabetes Mellitus, Dislipidemia and
      Hypertension. Insulin Resistance (IR) appears as the common etiological
      mechanism. AIM: To describe metabolic complications associated to obesity in a
      group of Chilean children and to correlate them with IR, estimated through the
      homeostasis model assessment index (HOMA). SUBJECTS AND METHODS: We studied 88
      children, 12 +/- 2.4 years old. Fifty two had severe obesity, 19 were overweight,
      and 17 had a normal weight (body mass index z score (BMIz): 4.7 +/- 1.6, 1.7 +/-
      0.5 and 0.2 +/- 0.6 respectively, p < 0.001). In obese children, an oral glucose
      tolerance test, measuring basal and 30 min insulin levels, was performed and
      serum lipid levels were measured. RESULTS: Eleven percent of the severely obese
      children were glucose intolerant, 67% had basal hyperinsulinemia (> 20 uU/ml) and
      79% had IR (HOMA > 3.8). These children also had a higher prevalence of acantosis
      nigricans than the overweight and normal counterparts (63, 10.5 and 0%
      respectively, p < 0.001), higher basal insulinemia: (24.4 +/- 10, 16.4 +/- 4 and
      12.2 +/- 3 mU/ml respectively) and HOMA (5.3 +/- 2, 3.4 +/- 0.8 and 2.3 +/- 0.5
      respectively, p < 0.001). By multiple stepwise regression analysis, BMIz was the
      only significant predictor for basal hyperinsulinemia, HOMA and diastolic blood
      pressure. Age and BMIz were independent predictors for systolic blood pressure.
      The strongest predictor for plasma lipid levels was the family history of
      dislipidemia. CONCLUSIONS: Obese children have a high prevalence of metabolic
      complications, which are related to the severity of obesity. Most of the severely
      obese children have hyperinsulinism and IR. BMIz is the principal predictor for
      high blood pressure. Familiar history is the better predictor for dislipidemia.

PMID- 12790075
TI  - [Prevalence of smoking among nurses in the Ninth region of Chile].
AB  - BACKGROUND: Smoking is noxious for health and is considered a public health
      priority. The prevalence of smoking is increasing, specially in women. Among
      nurses, its prevalence is 42.7%. AIM: To study the prevalence of smoking among
      Chilean nurses. MATERIAL AND METHODS: A cross sectional analysis of the
      prevalence of smoking among 290 female nurses living in 9th Region of Chile. A
      nicotine addiction scale was applied to smokers. RESULTS: The prevalence of
      smoking was 37.9% and the percentage of former smokers was 18.3%. Twenty percent
      of the sample was an occasional smoker. The starting age for the habit was
      between 17 and 20 years (49.4%). Twenty seven percent of nurses without children
      and 42% of those with children smoked. Having a couple or not, did not influence
      the smoking habit. Ninety percent of smokers had a very low addiction to
      nicotine. CONCLUSIONS: The prevalence of smoking obtained in a sample of nurses
      is similar to that obtained by former studies in other population samples in
      Chile.

PMID- 12790076
TI  - [Challenge testes for diagnosis and follow-up of children with food allergy].
AB  - BACKGROUND: The prevalence of food allergy increased worldwide in the last
      century. In Chile we became aware of this increase 10-15 years ago, after an
      epidemiological transition on health. AIM: To assess the most frequent clinical
      presentations of food allergy, results of circulating immunologlobulins (total
      IgE, specific IgE and IgG4 against cow's milk) and usefulness of a standardized
      challenge test. PATIENTS AND METHODS: Cross sectional assessment of 49 patients
      with cow's milk allergy (9 months-8 years of age), diagnosed at INTA, University
      of Chile between 1991-2001. RESULTS: All patients had cow's milk allergy and 37%
      of them were additionally intolerant to other allergens. Seventy eight percent
      had digestive symptoms and 84% had non digestive symptoms. The cause of
      consultation was a non-digestive manifestation in 16% of cases. At least one of
      the immunoglobulins (total IgE total, specific IgE or IgG4) was over the cut off
      point in 92% of patients. Between 1990-1995 six patients were diagnosed with
      cow's milk allergy and malabsorption syndrome. Suppression of the specific
      allergen resulted in disappearance of symptoms in 78% of patients; when a second
      dietary modification was necessary 87% of cases showed a good response. Thirty
      five of 56 challenge tests performed were done at home, by relatives, in a non
      controlled fashion. All of them were aimed to determine the desensitization of
      the child. CONCLUSIONS: Digestive and non-digestive manifestations were observed
      in these patients with food allergy. Although not designed to assess laboratory
      tests, results show that serum immunoglobulin determinations were helpful in
      guiding diagnosis. Mothers and relatives should be educated to accept diagnostic
      challenges and avoid carrying out non-controlled challenges.

PMID- 12790077
TI  - [Tc99m-pertechnetate thyroid scintigraphy in newborns with congenital
      hypothyroidism].
AB  - BACKGROUND: Congenital hypothyroidism is one of the most frequent endocrine
      diseases of the newborn and requires an early diagnosis to avoid its deleterious
      effects on neurological and intellectual functions. AIM: To evaluate thyroid
      scintigraphy (TS) findings in newborns with congenital hypothyroidism (CH),
      detected in the national program of newborn screening, which is working in Chile
      since 1992. MATERIAL AND METHODS: TS findings of 189 newborns with CH (68%
      female) were analyzed. Tc99m pertechnetate TS was performed at 19 +/- 11 days of
      life. The gland was classified as eutopic, ectopic or absence of contrast (AC).
      Eutopic glands were classified by visual and quantitative criteria as: normal,
      goiter and decreased contrast (DC). TS results were compared by gender and
      hormonal levels. RESULTS: Forty seven percent of newborns had ectopy, 29.1%
      eutopy and 24.3% AC. Eutopic gland predominated in males (44.2% vs 22.7%) and
      ectopy was more frequent in girls (53.1% vs 32.8%, p < 0.05). Newborns with AC
      had the most severe hormonal alterations, without gender differences. Newborns
      with normal TS had less hormonal alterations than those with goiter. CONCLUSIONS:
      TS allows an etiological classification of CH. Thyroid dysgenesis is the most
      frequent cause, most of which correspond to ectopy, especially in girls. Eutopic
      glands are present in one third of newborns with CH. Goiter predominates,
      especially in males.

PMID- 12790078
TI  - [Chronic lymphoproliferative syndromes in Chile. A prospective study in 132
      patients].
AB  - BACKGROUND: Chronic lymphoproliferative disorders include a variety of diseases
      which are often a diagnostic problem for clinical hematologists. AIM: To study
      prospectively the distribution and incidence of chronic lymphoproliferative
      disorders in Chile and compare them with those of other Western, Latin American
      and Oriental countries. PATIENTS AND METHODS: A group of 132 patients were
      studied in a 36 months period (1999-2001), with a panel of monoclonal antibodies.
      A score for chronic lymphocytic leukemia was employed to differentiate it from
      other B-cell disorders. RESULTS: The median age was 63 years old (range 32-94).
      Most patients had B-cell tumors (109) and the rest (23), T-cell tumors (82% vs
      18%). Forty five percent of patients with B-cell tumors had a chronic lymphocytic
      leukemia (CLL), while the others were disseminated lymphomas. The incidence of T
      cell tumors was slightly higher than that of other Western countries. Noteworthy
      is that the most common of these disorders was adult T cell leukemia/lymphoma
      (ATLL), in concordance with the high HTLV-1 seroprevalence in Chile. CONCLUSIONS:
      A morphologic, immunophenotypic and pathological study in a large number of
      patients with chronic lymphoproliferative disorders in Chile, shows a relatively
      low incidence of CLL when compared to other chronic B-cell tumors and a high
      representation of ATLL associated to HTLV-1 infection, compared with other
      Western countries. The lower incidence of CLL in our study might be due to
      patient's selection and/or underdiagnosis of this disease as a substantial
      proportion of CLL are asymptomatic.

PMID- 12790079
TI  - [Antifungal susceptibility of yeasts by Etest. Comparison of 3 media].
AB  - BACKGROUND: The increasing frequency of systemic fungal infections and the
      emergency of secondary resistance to antifungals in the lasts years, has
      stimulated the use of methods for antifungal susceptibility testing. Etest is an
      easily performed quantitative method that has a good agreement with the broth
      microdilution reference method (NCCLS), if appropriate media are used. AIM: To
      compare the susceptibility to Amphotericin B (AmB) and Fluconazole (Flu) of 22
      opportunistic yeast isolates (C albicans (7), C tropicalis (9), C parapsilosis
      (3) and Cryptococcus neoformans (3) by Etest, using three different media and to
      choose the best medium for each tested drug. The studied media were RPMI 1640,
      Casitone (Cas) and Sabouraud. RESULTS: The interpretation of minimal inhibitory
      concentration (MIC) endpoints on Sabouraud was difficult for AmB. The American
      Type Culture Collection (ATCC) strains MICs were out of the acceptable range in
      this medium. RPMI and Cas were suitable media to test AmB and Flu, but best
      endpoints were obtained for AmB in RPMI and Flu in Cas. CONCLUSIONS: The use of
      appropriate media for each antifungal drug optimizes the MIC readings by Etest.
      AmB should be tested in RMPI and Flu in Cas. Sabouraud must not be used.

PMID- 12790081
TI  - [Acute traumatic transection of the thoracic aorta: endovascular treatment].
AB  - Traumatic rupture of the aorta has a near 80% mortality. Most patients die on the
      site of the accident. Conventional surgical repair of these lesions has a high
      morbidity and mortality, generally associated to the severity of associated
      lesions. Over the last decade, endovascular treatment has become an effective
      therapeutic alternative. We report a 40 years old male, that suffered a traumatic
      rupture of the descending thoracic aorta in a car accident. A successful
      endovascular repair was performed, installing an endoprothesis on the site of the
      lesion, using a femoral artery approach. The patient had a good postoperative
      evolution and was discharged from the hospital once complete rehabilitation of
      his associated lesions was obtained.

PMID- 12790080
TI  - [X-linked hyper-IGM syndrome associated to sclerosing cholangitis and gallbladder
      neoplasm: clinical case].
AB  - We report a 11 years old male diagnosed as a X-linked hyper-IgM syndrome that
      presented with recurrent infections and sclerosing cholangitis and later
      developed a gallbladder cancer. Immunological evaluation showed decreased levels
      of serum IgG and IgA with elevated levels of IgM. Study of CD40 ligand expression
      on mitogen activated peripheral blood mononuclear cells revealed total absence of
      this marker on T lymphocytes. Molecular analysis detected, in the patient and his
      mother, a nonsense mutation in exon 1 of the transmembrane segment of the CD40
      ligand. He also presented elevation of alkaline phosphatases and mild elevation
      of liver enzymes. Liver biopsy demonstrated the presence of idiopathic sclerosing
      cholangitis. The patient was started on monthly IVIG therapy at 400 mg/kg, as
      well as ursodeoxycholic acid and vitamin E, with normalization of his IgG and IgM
      levels a decrease in the incidence of infections and normalization of liver
      function. Three years after diagnosis, we detected the presence of polyps inside
      the gallbladder that were reported at biopsy as adenocarcinoma. He underwent
      hepatic bisegmentectomy (VI B-V) and local lymphadenectomy.

PMID- 12790082
TI  - [Mucolipidoses type II. Case report].
AB  - We report a female newborn with type II mucolipidoses. This condition is
      characterized clinically by Hurler like features, progressive psychomotor
      retardation and death during the first or second year of life. Most cases present
      during the first year of life, with poor weight gain and coarse facies features.
      The cause of this rare autosomal recessive hereditary disease is the deficiency
      of the enzyme N-acetylglucosamine-1-phosphotransferase, required for the
      synthesis of mannose-6-phosphate, the ligand that allows the transport of acid
      hydrolases into lysosomes. The patient had clinical features commonly found in
      mucolipidosis II, including disproportionate dwarfism, retarded psychomotor
      development, coarse facies features, gibbous and restricted joint mobility. The
      diagnosis was proved by an extremely elevated activity of lysosomal enzymes in
      the serum, secondary to non-regulated secretion and subsequent intracellular
      depletion of these proteins. The child suffered recurrent pneumonia and died at
      22 months of age.

PMID- 12790084
TI  - [Looking for the physicians that our countries need: emphasis on communication
      and training of academics].
AB  - Changes in physicians education and practice induce, nowadays persistent
      modifications in program's curricula and contents and in learning methodologies,
      in almost all medical schools and countries. In many of these, and in Chile, this
      process shows some peculiarities due to the unusual proliferation of medical
      schools and their differing proposals about the profile of the professional
      training based on epidemiological considerations and teaching resources. The
      institutional initiatives leading to reforms, have defined quality and pertinence
      of these programs and profiles, as it has been the case of the curricular renewal
      in the University of Chile School of Medicine. Relevant to this reform have been:
      1) the introduction of communication skills, pursuing to increase humanistic
      contents, to improve patient doctor relationship and to accomplish the actual
      goals of medicine, and 2) capacitating the faculty in the proper disciplines and
      competencies, for better application of new knowledge and teaching tools to
      improve learning of the health professionals. Prospective evaluation of these
      changes will allow us to assess, with best evidence, its definitive role, that is
      momentarily availed by student's satisfaction.

PMID- 12790083
TI  - [Income inequality and self rated health: an analysis from a contextual
      perspective in Chile].
AB  - BACKGROUND: The correlation between income inequality and life expectancy was
      demonstrated 10 years ago, but later, several studies suggested that the negative
      impact of a low economic income on the health status was disappearing. AIM: To
      assess the independent effects of community income inequality on self rated
      health in Chile. MATERIAL AND METHODS: Multilevel analysis of the 2000 National
      Socio Economic Characterization Survey (CASEN) data from Chile. Individual level
      information included self rated health, age, sex, ethnicity, marital status,
      education, income, type of health insurance and residential setting
      (urban/rural). Community level variables included the Gini coefficient and median
      income. The main outcome measure was dichotomized self rated health (0 if
      excellent, very good or good; 1 if fair or poor). RESULTS: 101,374 individuals
      (at level 1) aged 18 and above, nested within 285 communities (at level 2) and 13
      regions (at level 3) were studied. Controlling for a range of individual level
      predictors, a significant gradient was observed between income and poor self
      rated health, with very poor most likely to report poor health (10.5%) followed
      by poor (9.5%) low (9%) middle (7%), high (6%) and very high (4.5%) income
      earners. Controlling for individual and community effects of income, a
      significant non linear effect of community income inequality was observed, with
      the most unequal communities being associated with approximately 5% higher
      likelihood of reporting poor health compared to the most equal communities.
      CONCLUSIONS: Individual income does not explain any of the between community
      differences and neither does it wash the significant effects of income inequality
      on poor self rated health. The contextual effect of inequality is almost as large
      as the differential observed in poor health comparing the very poor to the very
      rich individual income categories.

PMID- 12790085
TI  - [Why an Academic Department of Family Medicine?].
AB  - Over the last fifty years, Family Medicine has became not only an important part
      of many health systems around the world but also an established academic
      discipline. However, in the Iberoamerican context its development has been slow
      and with a number of difficulties. After a decade of work at the Family and
      Community Medicine Programme of the Catholic University of Chile, the role of
      Family medicine as an academic discipline requires a reflection. A definition of
      Family Medicine is advanced in line with a recent proposal of WONCA Europe
      including some fundamental aspects in the practice of any family doctor. A set of
      criteria for considering a medical subject as a discipline is analyzed and
      discussed with reference to Family Medicine. A unique field of action, an
      established body of knowledge, a set of analytical techniques, an specific area
      of research, its own philosophy, and a training which is intellectually rigorous,
      are all criteria that Family Medicine fulfills. Family Medicine is a medical
      discipline with a clear definition and it can be considered an academic
      discipline. Therefore, it is possible to establish an academic department within
      a Faculty of Medicine in Chile, which will contribute to a more balanced and
      complete medical education in the country.

PMID- 12790086
TI  - [Perception of angular velocity as a sensorimotor function of the shoulder
      complex].

PMID- 12790087
TI  - Synthesis of the mixed lithium-potassium-(bis)magnesium N-metallated/N, C
      dimetallated amide [Li2K2Mg4[But(Me3Si)N]4[But[Me2(H2C)Si]N]4]: an inverse crown
      molecule with an atomless cavity.
AB  - Unlike previous members of the inverse crown family, which are heterobimetallic
      and have cationic rings surrounding anionic cores, the title compound is
      heterotrimetallic and its "guest" anion is intramolecularly stitched into the
      complex fused-ring structure of its cationic "host".

PMID- 12790088
TI  - Synthesis, structure and reductive dechlorination of the C-centred
      phosphorus(III) beta-diketiminate PCl(Ph)L [L = C[C(Me)NC6H3Pri2(
      2),6][C(Me)NHC6H3Pri2(-2),6]].
AB  - Treatment of the beta-diketimine HL with successively LiBun and PCl2Ph gave the
      first C-centered monodentate beta-diketiminate PCl(Ph)L 1; with C8K 1 underwent
      reductive dechlorination yielding 2, a novel N-PIII-PIII-C=C heterocycle.

PMID- 12790089
TI  - [BHV-1 and BVDV eradication in Germany: a contagious hygienic challenge].

PMID- 12790090
TI  - [Tick-borne diseases and ecosystem modifications in Lorraine].

PMID- 12790091
TI  - Effect of visible light on the recovery of Streptomyces griseus conidia from
      ultra-violet irradiation injury.

PMID- 12790092
TI  - Reactivation of ultra-violet-inactivated bacteriophage by visible light.

PMID- 12790093
TI  - Marine sponges as biomonitor of polychlorobiphenyl contamination: concentration
      and fate of 24 congeners.
AB  - The aim of this study was first to assess the relevance of a marine sponge,
      Spongia officinalis, as a biomonitor of PCB. Twenty-four chlorobiphenyl congeners
      have been measured along a pollution gradient both in sponges and seawater. S.
      officinalis displays a capacity to accumulate all types of congeners. The highest
      concentration factors were found for hexa- and heptachlorobiphenyls.
      Concentrations recorded in sponges agreed quite well with the PCB concentrations
      of study sites. The prevalence of CB138 and CB153 definitely demonstrated the
      urban origin of the PCB detected, despite the ban on their production and the
      existence of a wastewater treatment plant since 1987. The CB138/CB153 ratio is
      approximately 1.2 in commercial mixtures as well as in seawater. In sponges, this
      ratio varies strongly in space and time, from 1 in sponges at the most polluted
      site to 0.3 at the reference site. This change in the ratio of these two very
      persistent congeners, which is not observed in seawater, indicates a metabolism
      of CB138 in sponges. As it was recently demonstrated for nonpersistent organic
      contaminants, sponges might well be able to degrade PCB, but further work is
      needed to identify the processes involved.

PMID- 12790094
TI  - [About anterior resections of the rectum].

PMID- 12790095
TI  - [Trends of stomatology towards the 21st century in China].

PMID- 12790096
TI  - "Quantitative analysis of human heart valves: does anorexigen exposure produce a
      distinctive morphological lesion?" by McDonald PC, et all.

PMID- 12790098
TI  - [Immunization against dental caries: current strategies].

PMID- 12790100
TI  - [Fetal monitoring development and current status].

PMID- 12790101
TI  - [Summary of national symposium on fetal monitoring].

PMID- 12790102
TI  - [Current state and prospect of molecular pathology of lung cancer].

PMID- 12790104
TI  - In commemoration of Alexander Evseevich Braunstein (1902-1986).

PMID- 12790103
TI  - [Proceedings of the Conference Celebrating the Certificate of Poliomyelitis
      Eradication in the European Region. 8 October 2002, Warsaw, Poland].

PMID- 12790105
TI  - Disease alert. SARS--severe acute respiratory syndrome.

PMID- 12790106
TI  - Disease management to population-based health: steps in the right direction?
AB  - This issue brief reviews the evolution of the disease management model and the
      ways it relates to care coordination and case management approaches. It also
      looks at examples of population-based disease management programs operating in
      both the private and public sectors and reviews the evidence of their success.
      Finally, the paper considers the policy implications of adapting this model to a
      Medicare fee-for-service population.

PMID- 12790107
TI  - [Research progression of nuclear transcription factor-kappaB].

PMID- 12790108
TI  - [Pathological diagnosis of viral hepatitis and liver carcinoma - progress and
      problems].

PMID- 12790109
TI  - Practice development: what are we learning from our British partners?

PMID- 12790111
TI  - [Display technique for phage antibody].

PMID- 12790110
TI  - [Heparanase and neoplasm metastasis].

PMID- 12790112
TI  - [The precancerous lesions and early carcinoma of uterine cervix].

PMID- 12790113
TI  - [The early diagnosis of pancreatic carcinoma].

PMID- 12790114
TI  - [The relationship between promoters of insulin like growth factor-II and
      hepatocellular carcinogenesis].

PMID- 12790115
TI  - [The precursor lesions and microinvasive adenocarcinoma of cervical
      adenocarcinoma].

PMID- 12790116
TI  - [Today and tomorrow of the development of pathology].

PMID- 12790118
TI  - [Improving research level of molecular pathology in the coming century].

PMID- 12790117
TI  - Pleiotropic actions of sphingosine-1-phosphate.
AB  - Sphingosine-1-phosphate (SIP) is a bioactive sphingolipid metabolite that
      regulates diverse cellular responses including, growth, survival, cytoskeleton
      rearrangements and movement. SIP plays an important role during development,
      particularly in vascular maturation and has been implicated in pathophysiology of
      cancer, wound healing, and atherosclerosis. This review summarizes the evidence
      showing that signaling induced by SIP is complex and involves both intracellular
      and extracellular actions. The intracellular effects of SIP remain speculative
      awaiting the identification of specific targets whereas the extracellular effects
      of SIP are clearly mediated through the activation of five specific G protein
      coupled receptors, called S1P1-5. Recent studies demonstrate that intracellular
      generated SIP can act in a paracrine or autocrine manner to activate its cell
      surface receptors.

PMID- 12790119
TI  - Cross-cultural competency in emergency medicine.

PMID- 12790120
TI  - [Basic and clinical investigations of hypertension-induced renal disease].

PMID- 12790121
TI  - Critical care training for emergency physicians.

PMID- 12790122
TI  - [The clinical study of systemic inflammatory response syndrome].

PMID- 12790123
TI  - Mild hypothermia in resuscitation: a historical perspective.

PMID- 12790124
TI  - Hopelessly complex.

PMID- 12790127
TI  - Another hazard of college drinking: the black light concoction.

PMID- 12790128
TI  - New ways of interfering with HCV replication.

PMID- 12790130
TI  - [Quality control and quality assurance in histo-pathology laboratories].

PMID- 12790129
TI  - Of chimps and men--finding the path to an HCV vaccine.

PMID- 12790131
TI  - [To improve as a whole the quality of diagnostic pathology].

PMID- 12790132
TI  - [Summary of the 2nd national conference on diagnostic pathology and the
      application of current technology in pathological diagnosis (Editorial Committee,
      Chinese Journal of Pathology)].

PMID- 12790133
TI  - [Bioregulation mechanism of cell apoptosis].

PMID- 12790134
TI  - [Microdissection technique used in the research of tumors].

PMID- 12790135
TI  - Against a role of lactic acid on the generation of the exercise pressor reflex.

PMID- 12790136
TI  - [Progress in pathological diagnosis of breast cancer].

PMID- 12790137
TI  - [Recent advances on molecular biology of diffuse astrocytoma].

PMID- 12790138
TI  - [Study on the molecular mechanism of histogenesis of colorectal carcinoma in
      recent years].

PMID- 12790139
TI  - [Histogenesis and nomenclature of stromal tumors in gastro-intestinal tract].

PMID- 12790141
TI  - On the 50th anniversary of solving the structure of DNA.

PMID- 12790140
TI  - [PTEN--a new tumor inhibitory gene].

PMID- 12790142
TI  - Rapamycin throws a master switch.

PMID- 12790143
TI  - TXG at SOT.

PMID- 12790144
TI  - Putting proteins in one place.

PMID- 12790145
TI  - Monitoring estrogenic effects: a genomics approach.

PMID- 12790147
TI  - [Clinical problems and strategies of interstitial lung diseases].

PMID- 12790146
TI  - Metals leave their mark: fingerprints of low-dose exposure.

PMID- 12790148
TI  - Long-term care waivers and the Independence Plus Initiative.

PMID- 12790149
TI  - The effect of retiring dentists.

PMID- 12790151
TI  - Miss Manners might not approve.

PMID- 12790150
TI  - Health care cost and access problems intensify: initial findings from HSC's
      recent site visits.
AB  - Continued high-cost trends are threatening the affordability of health insurance
      and many consumers' access to care. Early findings from the Center for Studying
      Health System Change's (HSC) 2002-03 site visits to 12 nationally representative
      communities show the retreat from tightly managed care continues to shape local
      health care markets. Employers are aggressively shifting higher health costs to
      workers, and absent tight managed care controls to limit the use of care and slow
      payment rate increases, hospitals and physicians in many markets are competing
      fiercely for profitable specialty services. These developments have sparked
      growing skepticism about the potential for market-led solutions to the cost,
      quality and access problems facing the health care system today.

PMID- 12790152
TI  - Vision impairment therapies.

PMID- 12790153
TI  - Aripiprazole.

PMID- 12790154
TI  - In vivo we trust.

PMID- 12790155
TI  - A new twist on the chiral switch.

PMID- 12790156
TI  - Brand versus generic medications: the money, the patient and the research.

PMID- 12790158
TI  - Smoking and tardive dyskinesia: lack of involvement of the CYP1A2 gene.
AB  - OBJECTIVE: To establish if there is an association between cigarette smoking and
      tardive dyskinesia (TD) in patients with schizophrenia and to evaluate the role
      of the CYP1A2 polymorphism in TD in patients of Chinese descent. METHOD: Two
      hundred and ninety-one patients diagnosed with schizophrenia according to DSM-IV
      criteria were included in the study. Dyskinesia was assessed by the Abnormal
      Involuntary Movement Scale and TD by the criteria of Schooler and Kane.
      Demographic and clinical data and information on smoking habits were collected,
      and patients of Chinese descent with a well established smoking history were
      subsequently genotyped for CYP1A2. RESULTS: Forty-three (41.3%) of the 104
      patients with a history of smoking and 52 (27.8%) of the 187 non-smokers were
      diagnosed with TD. The prevalence of TD was significantly higher among smokers
      than non-smokers (chi2 = 5.57, p = 0.018). Logistic regression using TD as the
      dependent variable revealed smokers to be at a significantly higher risk for TD
      (p < 0.005). Genotyping of smokers of Chinese descent for CYP1A2 polymorphism
      revealed no significant differences in the genotypic or allelic distribution
      between those with and without TD. CONCLUSIONS: Consistent with other studies,
      the prevalence of TD was significantly higher among smokers than non-smokers;
      however, we did not find an association between the C --> A genetic polymorphism
      of CYP1A2 and TD.

PMID- 12790157
TI  - Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and
      reward-related behaviours in animal models.
AB  - Cholecystokinin (CCK) is an abundant and widely distributed neuropeptide that
      plays a modulatory role in a variety of behaviours. This paper focuses on the
      role of CCK in modulating anxiety-related and reward-related behaviours in key
      brain regions of the amygdala and mesolimbic dopamine system, respectively. The
      role of CCK in mediating aspects of these behaviours has been studied in a
      variety of behavioural paradigms, but inconsistent results have led to confusion
      regarding the precise role of the receptor subtypes in mediating behaviour. The
      confusion in the literature may come in part from the diverse behavioural
      paradigms that are used, the differences in regional effects of CCK manipulations
      in different areas and at different receptor subtypes in these areas and the
      dependence of the behavioural outcome on the baseline state of arousal of the
      animal. Evidence on the role of CCK in anxiety-related and reward-related
      behaviours in various animal models indicates that CCK-B receptors in the
      basolateral amygdala are important mediators of anxiety-related behaviours and
      that CCK-A and CCK-B receptors in the nucleus accumbens are important in
      mediating different aspects of reward-related behaviour. Emphasis is placed upon
      the role of CCK as a neuromodulator that is recruited only under conditions of
      high frequency neuronal firing.

PMID- 12790159
TI  - Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled,
      crossover study.
AB  - OBJECTIVE: To assess the hypnotic effect of melatonin in patients with primary
      insomnia. METHOD: Ten patients (mean age 50 yr, range 30-72 yr) who met the DSM
      IV criteria for primary insomnia received, in random order, 0.3 mg of melatonin,
      1.0 mg of melatonin or placebo 60 minutes before bedtime. A crossover design was
      used so that each patient received each of the 3 treatments for a 7-day period
      (with a 5-day washout period between). After each 7-day treatment, night time
      electroencephalographic (EEG) records were collected, and each morning, subjects
      completed sleep logs and analogue-visual scales to document the amount and
      subjective quality of sleep. RESULTS: There were no significant differences in
      sleep EEG, the amount or subjective quality of sleep or side effects between the
      placebo, 0.3-mg melatonin or 1.0-mg melatonin treatments. CONCLUSION: Melatonin
      did not produce any sleep benefit in this sample of patients with primary
      insomnia.

PMID- 12790161
TI  - Hypothalamic-pituitary-thyroid system activity during lithium augmentation
      therapy in patients with unipolar major depression.
AB  - OBJECTIVE: Lithium augmentation is an established strategy in the treatment of
      refractory depression, but little is known about predictors of response and its
      mode of action. There is increasing evidence that low thyroid function indices
      within the normal range are associated with a poorer treatment response to
      antidepressants, but previous studies on the hypothalamic-pituitary-thyroid (HPT)
      system during lithium augmentation provide inconclusive results and have
      methodological limitations. This study aimed at exploring the role of thyroid
      function in lithium augmentation and used a prospective design that included a
      homogeneous sample of inpatients with unipolar major depressive disorder.
      METHODS: In 24 euthyroid patients with a major depressive episode who had not
      responded to antidepressant monotherapy of at least 4 weeks, we measured serum
      thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total
      thyroxine (T4) before (baseline) and during lithium augmentation therapy (follow
      up). The time point of the endocrinological follow-up depended on the status of
      response, which was assessed weekly with the Hamilton Depression Rating Scale, 17
      item version (HDRS17). Responders were reassessed immediately after response was
      determined, and non-responders after 4 weeks of lithium augmentation. RESULTS:
      There was a statistically significant change in thyroid system activity during
      lithium augmentation, with an increase of TSH levels and a decrease of peripheral
      T3 and T4 levels. However, there were no differences in any of the HPT hormones
      between responders and non-responders at baseline or at follow-up. CONCLUSIONS:
      The decrease of thyroid system activity during lithium treatment reflects the
      well-established "antithyroid" properties of lithium. However, it appears that
      thyroid status does not predict response to lithium augmentation in euthyroid
      patients before treatment.

PMID- 12790160
TI  - Spontaneously hypertensive rats: further evaluation of age-related memory
      performance and cholinergic marker expression.
AB  - OBJECTIVE: The spontaneously hypertensive rat (SHR), often used to study
      cardiovascular disease processes, may also be utilized to model certain central
      nervous system changes associated with memory disorders. Previous work in our
      laboratory indicated that central nicotinic acetylcholine receptors are markedly
      diminished and that memory-related task performance is impaired in this rodent
      phenotype. Due to the well-documented importance of the central cholinergic
      system to memory processes and its vulnerability to the effects of aging, it was
      of interest to measure other cholinergic markers and to further evaluate memory
      function in older SHRs. METHOD: Radial arm maze performance was used to assess
      working memory, quantitative receptor autoradiography with [3H]-pirenzipine, [3H]
      AFDX-384 and [3H]-epibatidine (combined with cytisine) was used to determine the
      densities of muscarinic-M1 and -M2 and nicotinic cholinergic alpha3 receptors,
      respectively. Immunoblotting experiments were also used to determine the
      expression of the presynaptic cholinergic markers, choline acetyltransferase and
      the vesicular acetylcholine transporter. RESULTS: Radial arm maze performance was
      impaired in hypertensive (compared with normotensive Wistar and Wistar-Kyoto)
      rats, regardless of age. M1 binding was increased in frontal and prefrontal
      cortical areas in SHR (p < 0.05), whereas M2 densities were higher in the
      hypertensive phenotype in the caudate putamen. A lower expression of alpha3
      containing nicotinic receptors was observed in the superior colliculus in SHRs.
      Age-related differences in the expression of the vesicular acetylcholine
      transporter were noted in the hippocampus. CONCLUSION: The SHR may be useful to
      model some aspects (particularly hypertension-related) of memory disorders,
      especially those in which cholinergic function is altered.

PMID- 12790162
TI  - Left with the voices or hearing right? Lateralization of auditory verbal
      hallucinations in schizophrenia.

PMID- 12790163
TI  - Tackling the problem of tuberculosis in cattle and people.

PMID- 12790164
TI  - Use of clinical information to predict the characteristics of bacteria isolated
      from clinical cases of bovine mastitis.
AB  - Farmers recorded the clinical signs of cows with clinical mastitis and submitted
      milk samples for bacteriological examination, so that the clinical signs could be
      correlated with the bacteriological findings. Odds ratios for the demeanour of
      the cow, the appearance of the milk, milk yield, udder texture, and the
      administration of parenteral antibiotics were calculated for mastitis cases
      classified in terms of their microbiology as either enterobacteriaceae, major
      Gram-positive pathogens, minor pathogens, 'no growths' or 'all other pathogens'.
      Animals infected with enterobacteriaceae had the highest odds of being reported
      as having a reduced milk yield, swollen or hard udders, watery milk and/or being
      systemically sick. A logistic regression model was used to predict the Gram
      staining characteristics of the bacteria causing clinical mastitis. The clinical
      findings found to be significant predictors in the model were the demeanour of
      the cow and its milk yield. The regression model was used as a basis for a
      predictive test. Using a test data set, the sensitivity of the test was 28 per
      cent, its specificity was 96 per cent, the positive predictive value was 74 per
      cent and the negative predictive value was 80 per cent. The overall accuracy of
      these predictions was 79 per cent.

PMID- 12790165
TI  - Aid to the antemortem diagnosis of Fell pony foal syndrome by the analysis of B
      lymphocytes.
AB  - Fell pony foals are affected by a congenital fatal immunodeficiency that commonly
      leads to anaemia and lymphopenia. Previous work has shown that the foals'
      circulating subpopulations of CD4 and CD8 T lymphocytes are unaffected. In this
      study it was shown that the mean population of B lymphocytes in 10 affected foals
      was less than 10 per cent of that in normal foals.

PMID- 12790166
TI  - Immunohistochemical study of the expression of E-cadherin in canine mammary
      tumours.
AB  - To investigate the possible role of E-cadherin in canine mammary tumours 20
      benign and 40 malignant tumours were evaluated by immunohistochemistry in
      formalin-fixed paraffin wax-embedded samples. In all the benign tumours, E
      cadherin was strongly expressed at the intercellular borders of epithelial cells,
      but it was less strongly expressed in 17 (43 per cent) of the malignant tumours.
      Furthermore, poorly differentiated carcinomas were less immunoreactive for E
      cadherin than moderately and well differentiated carcinomas.

PMID- 12790167
TI  - Analysis of feline urinary calculi and urethral plugs by infrared spectroscopy
      and scanning electron microscopy.
AB  - The chemical constituents of 34 feline urinary calculi and five urethral plugs
      were analysed by infrared spectroscopy. The analysis revealed that 18 (52.9 per
      cent) of the calculi contained magnesium ammonium phosphate hexahydrate
      (struvite) as the major component; 10 (29.4 per cent) contained complex ammonium
      urates (three of them also containing calcium phosphate, mainly on the surface);
      three were composed of calcium phosphates and three were composed mainly of
      calcium oxalate mono and dihydrates. The urethral plugs were composed primarily
      of struvite, but also contained large amounts of organic matter. The examination
      of 16 selected samples by scanning electron microscopy and electron dispersive x
      ray analysis revealed that their crystalline structures were similar to those of
      canine stones.

PMID- 12790168
TI  - Effect of sinus trephination on scintigraphy of the equine skull.

PMID- 12790169
TI  - Clinical and radiographic findings in six cattle with cervical diskospondylitis.

PMID- 12790170
TI  - Poor reproductive performance in pigs.

PMID- 12790171
TI  - FMD control strategies.

PMID- 12790172
TI  - FMD control strategies.

PMID- 12790173
TI  - Supply of veterinary medicines.

PMID- 12790174
TI  - Supply of veterinary medicines.

PMID- 12790175
TI  - RCVS consultation on practice standards.

PMID- 12790176
TI  - Testing for equine arteritis virus.

PMID- 12790178
TI  - Magnesium poisoning in cattle.

PMID- 12790177
TI  - Eastern Counties Veterinary Society.

PMID- 12790180
TI  - How much information is associated with a particular stimulus?
AB  - Although the Shannon mutual information can be used to reveal general features of
      the neural code, it cannot directly address which symbols of the code are
      significant. Further insight can be gained by using information measures that are
      specific to particular stimuli or responses. The specific information is a
      previously proposed measure of the amount of information associated with a
      particular response; however, as I show, it does not properly characterize the
      amount of information associated with particular stimuli. Instead, I propose a
      new measure: the stimulus-specific information (SSI), defined to be the average
      specific information of responses given the presence of a particular stimulus.
      Like other information theoretic measures, the SSI does not rely on assumptions
      about the neural code, and is robust to non-linearities of the system. To
      demonstrate its applicability, the SSI is applied to data from simulated visual
      neurons, and identifies stimuli consistent with the neuron's linear kernel. While
      the SSI reveals the essential linearity of the visual neurons, it also
      successfully identifies the well-encoded stimuli in a modified example where
      linear analysis techniques fail. Thus, I demonstrate that the SSI is an
      appropriate measure of the information associated with particular stimuli, and
      provides a new unbiased method of analysing the significant stimuli of a neural
      code.

PMID- 12790179
TI  - The Functional Brain Connectivity Workshop: report and commentary.
AB  - This report summarizes the presentations and discussions at a recent workshop
      entitled 'Functional Brain Connectivity', held in Dusseldorf, Germany. The aims
      of the workshop were to bring together researchers using different approaches to
      study connectivity in the brain, to enable them to share conceptual, mathematical
      and experimental ideas and to develop strategies for future work on functional
      integration. The main themes that emerged included: (1) the importance of
      anatomical knowledge in understanding functional interactions the brain; (2) the
      need to establish common definitions for terms used across disciplines; (3) the
      need to develop a satisfactory framework for inferring causality from functional
      imaging and electroencephalographic/magneto-encephalographic data; (4) the
      importance of analytic tools that capture the dynamics of neural interactions;
      and (5) the role of experimental paradigms that exploit the functional imaging of
      perturbations to cortical interactions.

PMID- 12790181
TI  - Sequence learning in differentially activated dendrites.
AB  - Differentially activated areas of a dendrite permit the existence of zones with
      distinct rates of synaptic modification, and such areas can be individually
      accessed using a reference signal which localizes synaptic plasticity and memory
      trace retrieval to certain subregions of the dendrite. It is proposed that the
      neural machinery required in such a learning/retrieval mechanism could involve
      the NMDA receptor, in conjunction with the ability of dendrites to maintain
      differentially activated regions. In particular, it is suggested that such a
      parcellation of the dendrite allows the neuron to participate in multiple
      sequences, which can be learned without suffering from the 'wash-out' of synaptic
      efficacy associated with superimposition of training patterns. This is a
      biologically plausible solution to the stability-plasticity dilemma of learning
      in neural networks.

PMID- 12790182
TI  - A computational model of cuneothalamic projection neurons.
AB  - The dorsal column nuclei, cuneatus and gracilis, play a fundamental role in the
      processing and integration of somesthetic ascending information. Intracellular
      and patch-clamp recordings obtained in cat in vivo have shown that cuneothalamic
      projection neurons present two modes of activity: oscillatory and tonic (Canedo
      et al 1998 Neuroscience 84 603-17). The former is the basis of generating, in
      sleep and anaesthetized states, slow, delta and spindle rhythms under the control
      of the cerebral cortex (Marino et al 2000 Neuroscience 95 657-73). The latter is
      needed, during wakefulness, to process somesthetic information in real time. To
      study this behaviour we have developed the first realistic computational model of
      the cuneothalamic projection neurons. The modelling was guided by experimental
      recordings, which suggest the existence of hyperpolarization-activated inward
      currents, transient low- and high-threshold calcium currents, and calcium
      activated potassium currents. The neuronal responses were simulated during (1)
      sleep, (2) transition from sleep to wakefulness and (3) wakefulness under both
      excitatory and inhibitory synaptic input. In wakefulness the model predicts a set
      of synaptically driven firing modes that could be associated with information
      processing strategies in the middle cuneate nucleus.

PMID- 12790183
TI  - Nonlinear ideal observation and recurrent preprocessing in perceptual learning.
AB  - Residual micro-saccades, tremor and fixation errors imply that, on different
      trials in visual tasks, stimulus arrays are inevitably presented at different
      positions on the retina. Positional variation is likely to be specially important
      for tasks involving visual hyperacuity, because of the severe demands that these
      tasks impose on spatial resolution. In this paper, we show that small positional
      variations lead to a structural change in the nature of the ideal observer's
      solution to a hyperacuity-like visual discrimination task such that the optimal
      discriminator depends quadratically rather than linearly on noisy neural
      activities. Motivated by recurrent models of early visual processing, we show how
      a recurrent preprocessor of the noisy activities can produce outputs which, when
      passed through a linear discriminator, lead to better discrimination even when
      the positional variations are much larger than the threshold acuity of the task.
      Since, psychophysically, hyperacuity typically improves greatly over the course
      of perceptual learning, we discuss our model in the light of results on the speed
      and nature of learning.

PMID- 12790184
TI  - Dynamics of neuronal populations: eigenfunction theory; some solvable cases.
AB  - A novel approach to cortical modelling was introduced by Knight and co-workers in
      1996. In their presentation cortical dynamics is formulated in terms of
      interacting populations of neurons, a perspective that is in part motivated by
      modern cortical imaging. The approach may be regarded as the application of
      statistical mechanics to neuronal populations, and the simplest exemplar bears a
      kinship to the Boltzmann equation of kinetic theory. The disarming simplicity of
      this linear equation hides the complex behaviour it produces. A purpose of this
      paper is to investigate and reveal its intricacies by treating a series of
      solvable special cases. In particular we will focus on issues that relate to the
      spectral analysis of the underlying operators. A fairly thorough treatment is
      presented for a simple, but still useful example, that has important consequences
      for more general situations.

PMID- 12790185
TI  - Network capacity analysis for latent attractor computation.
AB  - Attractor networks have been one of the most successful paradigms in neural
      computation, and have been used as models of computation in the nervous system.
      Recently, we proposed a paradigm called 'latent attractors' where attractors
      embedded in a recurrent network via Hebbian learning are used to channel network
      response to external input rather than becoming manifest themselves. This allows
      the network to generate context-sensitive internal codes in complex situations.
      Latent attractors are particularly helpful in explaining computations within the
      hippocampus--a brain region of fundamental significance for memory and spatial
      learning. Latent attractor networks are a special case of associative memory
      networks. The model studied here consists of a two-layer recurrent network with
      attractors stored in the recurrent connections using a clipped Hebbian learning
      rule. The firing in both layers is competitive--K winners take all firing. The
      number of neurons allowed to fire, K, is smaller than the size of the active set
      of the stored attractors. The performance of latent attractor networks depends on
      the number of such attractors that a network can sustain. In this paper, we use
      signal-to-noise methods developed for standard associative memory networks to do
      a theoretical and computational analysis of the capacity and dynamics of latent
      attractor networks. This is an important first step in making latent attractors a
      viable tool in the repertoire of neural computation. The method developed here
      leads to numerical estimates of capacity limits and dynamics of latent attractor
      networks. The technique represents a general approach to analyse standard
      associative memory networks with competitive firing. The theoretical analysis is
      based on estimates of the dendritic sum distributions using Gaussian
      approximation. Because of the competitive firing property, the capacity results
      are estimated only numerically by iteratively computing the probability of
      erroneous firings. The analysis contains two cases: the simple case analysis
      which accounts for the correlations between weights due to shared patterns and
      the detailed case analysis which includes also the temporal correlations between
      the network's present and previous state. The latter case predicts better the
      dynamics of the network state for non-zero initial spurious firing. The
      theoretical analysis also shows the influence of the main parameters of the model
      on the storage capacity.

PMID- 12790186
TI  - Optimal neural rate coding leads to bimodal firing rate distributions.
AB  - Many experimental studies concerning the neuronal code are based on graded
      responses of neurons, given by the emitted number of spikes measured in a certain
      time window. Correspondingly, a large body of neural network theory deals with
      analogue neuron models and discusses their potential use for computation or
      function approximation. All physical signals, however, are of limited precision,
      and neuronal firing rates in cortex are relatively low. Here, we investigate the
      relevance of analogue signal processing with spikes in terms of optimal stimulus
      reconstruction and information theory. In particular, we derive optimal tuning
      functions taking the biological constraint of limited firing rates into account.
      It turns out that depending on the available decoding time T, optimal encoding
      undergoes a phase transition from discrete binary coding for small T towards
      analogue or quasi-analogue encoding for large T. The corresponding firing rate
      distributions are bimodal for all relevant T, in particular in the case of
      population coding.

PMID- 12790187
TI  - Modular organization of adaptive colouration in flounder and cuttlefish revealed
      by independent component analysis.
AB  - Flounders and cuttlefish have an impressive ability to change colouration, for
      camouflage and, in the case of cuttlefish, for communication. We pursue the
      hypothesis that these diverse patterns are created by combining a small number of
      distinct pattern modules. Independent component analysis (ICA) is a powerful tool
      for identifying independent sources of variation in linear mixtures of signals.
      Two versions of ICA are used, one assuming that sources have independence over
      time, and the other over space. These reveal the modularity of the skin
      colouration system, and suggest how the pattern modules are combined in specific
      behavioural contexts. ICA may therefore be a useful tool for studying animal
      camouflage and communication.

PMID- 12790189
TI  - Pattern formation in intracortical neuronal fields.
AB  - This paper introduces a neuronal field model for both excitatory and inhibitory
      connections. A single integro-differential equation with delay is derived and
      studied at a critical point by stability analysis, which yields conditions for
      static periodic patterns and wave instabilities. It turns out that waves only
      occur below a certain threshold of the activity propagation velocity. An
      additional brief study exhibits increasing phase velocities of waves with
      decreasing slope subject to increasing activity propagation velocities, which are
      in accordance with experimental results. Numerical studies near and far from
      instability onset supplement the work.

PMID- 12790188
TI  - Application of Lempel-Ziv complexity to the analysis of neural discharges.
AB  - Pattern matching is a simple method for studying the properties of information
      sources based on individual sequences (Wyner et al 1998 IEEE Trans. Inf. Theory
      44 2045-56). In particular, the normalized Lempel-Ziv complexity (Lempel and Ziv
      1976 IEEE Trans. Inf. Theory 22 75-88), which measures the rate of generation of
      new patterns along a sequence, is closely related to such important source
      properties as entropy and information compression ratio. We make use of this
      concept to characterize the responses of neurons of the primary visual cortex to
      different kinds of stimulus, including visual stimulation (sinusoidal drifting
      gratings) and intracellular current injections (sinusoidal and random currents),
      under two conditions (in vivo and in vitro preparations). Specifically, we
      digitize the neuronal discharges with several encoding techniques and employ the
      complexity curves of the resulting discrete signals as fingerprints of the
      stimuli ensembles. Our results show, for example, that if the neural discharges
      are encoded with a particular one-parameter method ('interspike time coding'),
      the normalized complexity remains constant within some classes of stimuli for a
      wide range of the parameter. Such constant values of the normalized complexity
      allow then the differentiation of the stimuli classes. With other encodings (e.g.
      'bin coding'), the whole complexity curve is needed to achieve this goal. In any
      case, it turns out that the normalized complexity of the neural discharges in
      vivo are higher (and hence carry more information in the sense of Shannon) than
      in vitro for the same kind of stimulus.

PMID- 12790190
TI  - Iminodiacetic acid functionalised monolithic silica chelating ion exchanger for
      rapid determination of alkaline earth metal ions in high ionic strength samples.
AB  - Iminodiacetic acid has been covalently bonded to a bare silica monolith to
      produce the first reported high-performance monolithic chelating ion exchange
      column. Using the new column, separation and determination of traces of alkaline
      earth metal ions (low ppm) in high ionic strength samples (up to 2 M NaCl and KCl
      brines), could be achieved in under 40 s. At an eluent flow rate of 4 mL min(-1)
      retention time precision was < 1.2% (n = 9) for Mg(II) and Ca(II), with detector
      linearity (n = 5) over the range 2-10 mg L(-1) of between R2 = 0.985 and R2 =
      0.995. In 1 M KCl and NaCl brine samples, detection limits of 0.2 mg L(-1) were
      possible.

PMID- 12790191
TI  - Mobile phase compensation to improve NMR spectral properties during solvent
      gradients.
AB  - A solvent compensation method based on flow injection analysis is used to obtain
      high quality nuclear magnetic resonance (NMR) spectra during solvent gradients.
      Using a binary solvent system containing D2O and CD3OD, NMR line broadening and
      chemical shift changes are observed with a 10% methanol per min solvent
      composition gradient. However, by creating a second equal but reverse gradient
      and combining the two solvent gradients before the NMR detector, the composition
      of solvent reaching the NMR flow cell is kept constant. We demonstrate a system
      using flow injection analysis of combining solvent gradients and show constant
      NMR spectral performance as a function of time as the combined flow has a
      constant solvent composition irrespective of the initial solvent gradient. Using
      this approach, methods can be developed to measure high quality NMR spectra
      during on-flow gradient LC-NMR experiments. The ultimate ability of this approach
      depends on the ability to compensate for the disturbance of the solvent gradient
      and reverse gradient by a pair of LC columns (the analytical and reverse gradient
      columns).

PMID- 12790192
TI  - Evaluation of a reversed-phase column (supelcosil LC-ABZ) under isocratic and
      gradient elution conditions for estimating octanol-water partition coefficients.
AB  - The solvation parameter model is used to identify suitable chromatographic models
      for estimating the octanol-water partition coefficient for neutral compounds of
      varied structure by reversed-phase liquid chromatography. The stationary phase
      Supelcosil LC-ABZ with methanol-water mobile phases affords a series of suitable
      correlation models for estimating the octanol-water partition coefficient (log
      KOW) under isocratic and gradient elution conditions. Isocratic separations with
      mobile phase compositions containing from about 25 to 40% (v/v) methanol provide
      the most accurate results for log KOW values in the range -0.1 to 4.0. Gradient
      separations programmed from 5 to 100% (v/v) methanol are suitable for faster
      separations of compounds with large log KOW values. The standard error in the
      estimate for the regression models of the predicted log KOW values against
      literature values are 0.135 log units for the 30% (v/v) methanol-water isocratic
      system and 0.263 log units for the methanol-water gradient system. Isocratic
      retention factors predicted from two gradient separations with gradient times of
      15 and 45 min afford a poorer fit for the correlation models between log KOW and
      the estimated retention factors than that of either the above isocratic and
      gradient models. Plots of the retention factor (log k) as a function of mobile
      phase composition are generally non-linear. Values of log kw obtained by non
      linear extrapolation to a volume fraction of 0% (v/v) methanol do not afford a
      useful model for estimating log KOW.

PMID- 12790193
TI  - Analysis of polycyclic aromatic hydrocarbons in soil and sediment with on-line
      coupled pressurised hot water extraction, hollow fibre microporous membrane
      liquid-liquid extraction and gas chromatography.
AB  - Pressurised hot water extraction (PHWE) was coupled on-line via hollow fibre
      microporous membrane liquid-liquid extraction (HF-MMLLE) to gas chromatography
      (GC) and applied in the analysis of polycyclic aromatic hydrocarbons (PAHs) in
      soil and sediment. In this combination, the MMLLE unit serves as a trapping
      device for the extracted compounds. Simultaneously it cleans and concentrates the
      extract, which is then transferred on-line to the GC. No extra clean-up steps are
      required between the trapping and the transfer to GC. The on-line system gives
      excellent sensitivity while allowing small sample size. The method was linear,
      with limits of detection in the range 50-890 pg and limits of quantification 0.11
      1.22 microg g(-1). The concentration enrichment factors obtained with the method
      ranged from 9 to 55. Comparison of the results with those obtained by other
      techniques confirmed the good performance.

PMID- 12790195
TI  - Isotope dilution analysis as a definitive tool for the speciation of organotin
      compounds.
AB  - Different spike solutions available for the determination of butyltin compounds
      by isotope dilution analysis are described and applied for the determination of
      butyltin compounds in PACS-2 certified reference material. Additionally, those
      spike solutions were evaluated during the course of an interlaboratory exercise
      organised by the National Research Council of Canada and the Laboratory of the
      Government Chemist (UK) in order to quantify tributyltin in a pilot sediment. The
      aim of this project was to evaluate the capabilities of isotope dilution mass
      spectrometry to reduce the uncertainty in the certification of Reference
      Materials for the speciation of organotin compounds. All participants were
      supplied with a 17Sn-enriched TBT solution from the Laboratory of the Government
      Chemist (UK). In our case, we performed the analysis of the pilot sediment also
      using a 119Sn enriched spike (mixed mono-, di- and tributyltin) and a 118Sn-119Sn
      double spike. The use of these additional spike solutions not only allowed the
      determination of monobutyltin and dibutyltin in the pilot sediment but also the
      evaluation and correction of possible extraction-derived rearrangement reactions.
      An excellent agreement amongst our results and between the participants was
      obtained with a precision of 8.4% RSD at a level of ca. 80 ng TBT g(-1) (as Sn).

PMID- 12790194
TI  - A method for detecting O-glycanase in biological samples using a combination of
      MALDI-TOF mass spectrometry and time-resolved fluorimetry.
AB  - O-Glycans (mucin type oligosaccharides) are ubiquitously found in various
      glycoproteins such as mucin-type glycoproteins on the surface of various
      digestive organs. In the present paper, we propose a method for detecting O
      glycanase which catalyzes the hydrolysis of the O-glycan linkage between
      oligosaccharides and serine/threonine residues of mucin-type glycoprotein. As the
      substrate for O-glycanases, we chose glycopeptides containing O-glycans derived
      from bovine fetuin. The present method is divided into two parts. At the initial
      stage, the presence of O-glycanase was confirmed by observing characteristic ions
      due to O-glycans and peptides released from the glycopeptide by matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. In the
      second step, europium labeled O-glycosylated peptide permits more detailed
      analysis such as enzyme kinetics. We demonstrated the usefulness of the present
      method using O-glycanase (Streptococcus pneumoniae) as model enzyme. The present
      approach can easily confirm the presence of O-glycanase by detecting both
      deglycosylated peptides and O-glycans, even if contaminating peptides or
      glycosidases are present in crude biological samples.

PMID- 12790196
TI  - Trace humic and fulvic acid determination in natural water by cloud point
      extraction/preconcentration using non-ionic and cationic surfactants with FI-UV
      detection.
AB  - A preconcentration and determination method for humic and fulvic acids at trace
      levels in natural water samples was developed. Cloud point extraction was
      successfully employed for the preconcentration of humic acid (HA) and fulvic acid
      (FA) prior to the determination by using a flow injection (FI) system coupled to
      a spectrophotometric UV-Vis detector. The quantitative extraction of HA and FA
      within the pH range 1-12 was obtained by neutralization of the anionic charge on
      the humic substances with a cationic surfactant, hexadecyltrimethylammonium
      bromide (CTAB). This generated a hydrophobic species that was subsequently
      incorporated (solubilized) into the micelles of a non-ionic surfactant
      polyethylene glycol, tert-octylphenyl ether (Triton X-114). The FI method for HA
      and FA determination was developed by injection of 100 microl of the extracted
      surfactant-rich phase using an HPLC pump with spectrophotometric detection at 350
      nm. A 50 ml sample solution preconcentration allowed an enrichment factor of 167.
      The limit of detection (LOD) obtained under the optimal conditions was 5 microg
      l(-1). The precision for ten replicate determinations at 0.2 mg l(-1) HA was 3.1%
      relative standard deviation (RSD), calculated from the peak heights. The
      calibration using the preconcentration system for HA and FA was linear with a
      correlation coefficient (r2) of 0.9997 at levels near the detection limits up to
      at least 1 mg l(-1). The method was successfully applied to the determination of
      HA and FA in natural water samples (river water).

PMID- 12790197
TI  - The production and characterisation of an antibody to detect the coccidiostat
      toltrazuril and its metabolite ponazuril.
AB  - The production of an antibody to detect toltrazuril or its metabolite ponazuril
      is complicated due to structural constraints of conjugating these coccidiostats
      to a carrier protein. Therefore a search was carried out for a compound that
      shared a common substructure to use as an antigen mimic. The chosen compound,
      trifluoraminoether, was conjugated to two carrier proteins (HSA and BTG) and used
      in the immunisation of six rabbits. Two immunogen doses (1 mg and 0.1 mg) were
      also used. All six rabbits produced an immunological response to the hapten
      regardless of the carrier protein or immunogen dose used. The most sensitive
      polyclonal antibody produced, designated R609, was subsequently characterised.
      This antiserum exhibited an IC50 of 18 ng ml(-1) using a competitive ELISA
      format. Cross reactivity studies show that this serum is specific for toltrazuril
      and its metabolites (toltrazuril sulfoxide and toltrazuril sulfone) but does not
      cross-react with other coccidiostats such as halofuginone, nitroimidazoles or
      nicarbazin. This is the first reported production of an antibody capable of
      specifically binding toltrazuril and ponazuril.

PMID- 12790198
TI  - Nanometer fluorescent hybrid silica particle as ultrasensitive and photostable
      biological labels.
AB  - Nanometer-sized fluorescent hybrid silica (NFHS) particles were prepared for use
      as sensitive and photostable fluorescent probes in biological staining and
      diagnostics. The first step of the synthesis involves the covalent modification
      of 3-aminopropyltrimethoxysilane with an organic fluorophore, such as fluorescein
      isothiocyanate, under N2 atmosphere for getting a fluorescent silica precursor.
      Then the NFHS particles, with a diameter of well below 40 nm, were prepared by
      controlled hydrolysis of the fluorescent silica precursor with tetramethoxysilane
      (TMOS) using the reverse micelle technique. The fluorophores are dispersed
      homogeneously in the silica network of the NFHS particles and well protected from
      the environmental oxygen. Furthermore, since the fluorophores are covalently
      bound to the silica network, there is no migration, aggregation and leakage of
      the fluorophores. In comparison with common single organic fluorophores, these
      particle probes are brighter, more stable against photobleaching and do not
      suffer from intermittent on/off light emission (blinking). We have used these
      newly developed NFHS particles as a fluorescent marker to label antibodies, using
      silica immobilization method, for the immunoassay of human alpha-fetoprotein
      (AFP). The detection limit of this method was down to 0.05 ng mL(-1) under our
      current experimental conditions. We think this material would attract much
      attention and be applied widely in biotechnology.

PMID- 12790199
TI  - Voltammetric detection of lead(II) and mercury(II) using a carbon paste electrode
      modified with thiol self-assembled monolayer on mesoporous silica (SAMMS).
AB  - The anodic stripping voltammetry at a carbon paste electrode modified with thiol
      terminated self-assembled monolayer on mesoporous silica (SH-SAMMS) provides a
      new sensor for simultaneous detection of lead (Pb2+) and mercury (Hg2+) in
      aqueous solutions. The overall analysis involved a two-step procedure: an
      accumulation step at open circuit, followed by medium exchange to a pure
      electrolyte solution for the stripping analysis. Factors affecting the
      performance of the SH-SAMMS modified electrodes were investigated, including
      electrode activation and regeneration, electrode composition, preconcentration
      time, electrolysis time, and composition of electrolysis and stripping media. The
      most sensitive and reliable electrode contained 20% SH-SAMMS and 80% carbon
      paste. The optimal operating conditions were a sequence with a 2 min
      preconcentration period, then a 60 s electrolysis period of the preconcentrated
      species in 0.2 M nitric acid, followed by square wave anodic stripping
      voltammetry from -1.0 V to 0.6 V in 0.2 M nitric acid. The areas of the peak
      responses were linear with respect to metal ion concentrations in the ranges of
      10-1500 ppb Pb2+ and 20-1600 ppb Hg2+. The detection limits for Pb2+ and Hg2+
      were 0.5 ppb Pb2+ and 3 ppb Hg2+ after a 20 min preconcentration period.

PMID- 12790200
TI  - Physical adsorption of N,N'-diphenyl-p-phenylenediamine onto carbon particles:
      application to the detection of sulfide.
AB  - The derivatisation of carbon powder by physical adsorption of N,N'-diphenyl-p
      phenylenediamine (DPPD) onto the surface of graphite particles (1-2 microm
      diameter) results in usefully functionalised carbon. The derivatised carbon
      powders have been studied using cyclic voltammetry by (i) abrasive immobilisation
      of the powder onto a basal plane pyrolytic graphite electrode (bppg) and (ii) by
      the manufacture of carbon-epoxy electrodes containing the derivatised carbon. The
      electrochemical response of the DPPD modified carbon has been examined in the
      presence of sulfide and possible reactions identified for the behaviour of each
      electrode substrate. The analytical application of the carbon-epoxy electrode for
      the sensing of sulfide is reported.

PMID- 12790201
TI  - Electrochemiluminescence enzyme immunoassay for TNT.
AB  - Details of an electrochemiluminescence (ECL) enzyme immunoassay for TNT (2,4,6
      trinitrotoluene) are reported. The design and construction of a computer
      controlled flow injection electrochemiluminometer in which the immunoassays are
      carried out is described. This system is used to select and pump solutions
      through a flow cell, which contains a gold working electrode as part of a three
      electrode arrangement. The deposition of a re-usable immunosorbent dextran
      surface anchored to a gold surface in the flow cell by chemiadsorbed thiol groups
      is described. Antibodies are labeled with the enzyme glucose oxidase and used in
      competitive immunoassays in which the separation step is carried out by
      concentrating unbound antibodies on the immunosorbent surface. Hydrogen peroxide
      generated by the enzyme label when glucose is pumped through the flow cell is
      detected using luminol ECL. Light intensity was inversely proportional to the
      concentration of TNT in the sample in the range 0-100 ppb. The results are
      compared with colorimetric ELISA's carried out using the same reagents, and
      potential for developing a portable instrument for use in the field is discussed.

PMID- 12790202
TI  - Validation of the CALUX bioassay for the screening of PCDD/Fs and dioxin-like
      PCBs in retail fish.
AB  - The chemical-activated luciferase expression (CALUX) assay is a reporter gene
      assay that detects dioxin-like compounds based on their ability to activate the
      aryl hydrocarbon receptor (AhR) and thus expression of the reporter gene. In this
      paper, the CALUX assay was examined for its application in the screening of
      polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like
      polychlorinated biphenyls (dioxin-like PCBs) in retail fish. The sample extracts
      were cleaned up on a sulfuric acid-silica gel column followed by an activated
      carbon column, and the AhR activity of the separated PCDD/F and dioxin-like PCB
      fractions was determined using the assay. The quantitative limit for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) was 0.98 pg ml(-1) (0.19 pg assay(-1)
      in the standard curve, corresponding to 0.16 pg g(-1) of CALUX-based toxic
      equivalency (2,3,7,8-TCDD equivalents) in the tested sample. Recovery tests in
      which dioxins were added to fish samples resulted in acceptable recoveries (77
      117%). The CALUX assay performed well in the analysis of dioxins in fish samples
      and a comparative study revealed a strong correlation between the CALUX assay and
      high-resolution gas chromatography-high-resolution mass spectrometry analysis for
      the determination of PCDD/Fs (r = 0.89) and dioxin-like PCBs (r = 0.91) in retail
      fish (n = 22). These data revealed that the CALUX assay would be a useful
      screening method for PCDD/Fs and dioxin-like PCBs in retail fish.

PMID- 12790204
TI  - Confocal Raman microscopy of supercritical fluid dyeing of polymers.
AB  - Supercritical CO2 was used as a medium to introduce azo-dyes into polymers (PMMA
      and PET). Confocal Raman microscopy has been applied using dry metallurgical and
      oil objectives to measure the concentration of dye as a function of distance from
      the surface to the core of the polymer samples. A significant gradient of dye
      concentration normal to the surface, down to the depth of ca. 100 microm, has
      been observed. In addition, cross-sections of cut dyed polymer samples have been
      analysed using a conventional mapping approach. The comparison between confocal
      depth and conventional mapping approaches has demonstrated that the use of the
      oil objective can provide reliable qualitative information on dye distribution in
      these systems. These confocal Raman experiments demonstrate the potential of this
      method in applications to polymeric materials processed with supercritical
      fluids.

PMID- 12790203
TI  - Complete curve fitting of extraction profiles for estimating uncertainties in
      recovery estimates.
AB  - This paper reports the use of improved numerical approaches to modelling
      extraction profiles, and shows that the approach substantially reduces
      statistical prediction uncertainties compared to those obtained on the basis of a
      three-point extrapolation from the later part of the extraction curve. Numerical
      fitting of manually obtained polycyclic aromatic hydrocarbon extraction data to a
      spherical particle diffusion model showed uncertainties typically reduced by a
      factor of three (with extremes at 1.02 and 770). Application to pressurised fluid
      extraction study of pelletised poly(vinylchloride) containing 30 mass% di(2
      ethylhexyl)phthalate also showed good improvements. However, this high precision
      data showed small but significant lack of fit resulting in residual correlation
      and visibly biased prediction (more so than simple extrapolation). Re-fitting and
      uncertainty estimation using a first-order autoregression approximation to the
      covariance matrix produced more realistic uncertainty estimates and closer
      parameter estimates and is accordingly recommended for treating residual
      correlation from other causes, but did not entirely alleviate the problem.
      Different shape models (spherical, plane sheet and cylindrical) were applied
      without accounting fully for fitting error, and particle size effects were
      eliminated by modelling a simple size distribution. However, an approximate model
      based on linearly concentration-dependent diffusion coefficient showed excellent
      fit, confirming concentration-dependence as the most likely cause. This
      semiempirical model led to an uncertainty in total extractable material, at 0.2%
      of the total extractable value (with allowance for correlation). This is
      potentially good enough for recovery estimation and correction in certification
      of reference materials for validation purposes.

PMID- 12790205
TI  - Basic concepts of ion channel physiology and anaesthetic drug effects.
AB  - Ion channels regulate a diversity of physiological functions such as neuronal
      signalling, cardiac excitability and immune cell response. All of these systems
      may be affected during the conduct of general as well as local anaesthesia. Thus,
      the investigation of anaesthetic action on ion channels has become the focus of
      an increasing number of laboratory studies. Consequently, the concepts of ion
      channel physiology are becoming important for understanding the scientific and
      pharmacological basis of clinical anaesthesia. This brief guide is intended to
      help in understanding the increasing number of studies concerned with the effects
      of anaesthetic agents on ionic currents. The generation of ionic currents
      requires a complex molecular interplay of ions, ion channel proteins and lipid
      membranes. Anaesthetic agents frequently exhibit more than a single effect on ion
      channel function. Their effects can be described by quantifying the
      pharmacological alteration of ion channel activation, conductance and
      inactivation. Many physiological functions are directly influenced by ion
      channels. Pharmacological action on ion channels is thus fundamental to effects
      as well as side-effects of anaesthetic agents. The alteration of ion channel
      function by anaesthetic agents consequently determines their clinical effects.

PMID- 12790206
TI  - Pharmacological modification of sodium channels from the human heart atrium in
      planar lipid bilayers: electrophysiological characterization of responses to
      batrachotoxin and pentobarbital.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effects of barbiturates on
      batrachotoxin-modified sodium channels from different regions of the human heart.
      Single sodium channels from human atria were studied and compared with existing
      data from the human ventricle and from the central nervous system. METHODS:
      Sodium channels from preparations of human atrial muscle were incorporated into
      planar lipid bilayers in the presence of batrachotoxin, a sodium channel
      activator. The steady-state behaviour of single sodium channels was recorded in
      symmetrical 500 mmol NaCl before and after the addition of pentobarbital 0.34
      1.34 mmol. RESULTS: The batrachotoxin-treated human atrial sodium channel had an
      average single-channel conductance of 23.8 +/- 1.6 pS in symmetrical 500 mmol
      NaCl and a channel fractional open time of 0.83 +/- 0.06. The activation mid
      point potential was -98.0 +/- 2.3 mV. Extracellular tetrodotoxin (a specific
      sodium channel blocking agent) blocked these channels with a k(1/2) = 0.53
      micromol at 0 mV. Pentobarbital reduced the time average conductance of single
      atrial sodium channels in a concentration-dependent manner (ID50 = 0.71 mmol). In
      the same way, the steady-state activation was shifted to more hyperpolarized
      potentials (-10.6 mV at 0.67 mmol pentobarbital). CONCLUSIONS: The properties of
      batrachotoxin-modified sodium channels from human atrial tissue did not differ
      greatly from those described for ventricular sodium channels in the literature.
      Our data yielded no explanation for the observed functional diversity. However,
      cardiac sodium channels differ from those found in the central nervous system.

PMID- 12790207
TI  - Testing and modelling the interaction of alfentanil and propofol on the EEG.
AB  - BACKGROUND AND OBJECTIVE: For total intravenous anaesthesia an opioid is often
      combined with a hypnotic. A supra-additive interaction has been reported for
      clinical signs such as loss of consciousness or loss of the eyelash reflex. This
      study investigated the type of interaction of alfentanil and propofol on the
      electroencephalogram. METHODS: Twenty patients scheduled for abdominal surgery
      were enrolled in the study. Anaesthesia was induced and maintained with
      alfentanil and propofol. Each patient received a target-controlled infusion of
      alfentanil. Three target concentrations of 150, 225 and 300 ng mL(-1) were
      applied to each patient in random order. Propofol was added to the alfentanil
      infusion by a feedback system. The set point was the range of 1.5-2.5 Hz median
      frequency of the electroencephalogram. Four arterial blood samples were taken
      within the last 20 min of each period. The mean drug concentrations were used to
      determine the type of interaction and an isobole was estimated by fitting
      Bernstein spline functions to the data. RESULTS: In 17 patients, all three
      alfentanil target concentrations could be administered. The test for supra
      additivity as well as the isobole construction resulted in an additive type of
      interaction. The line of additivity cA/cA0 + cP/cP0 = 1 was best fitted for the
      values (standard deviation) cA0 = 1240 (51)ng mL(-1) and cP0 = 5.21 (0.36) microg
      mL(-1). CONCLUSIONS: The type of interaction between alfentanil and propofol on
      the electroencephalogram in the investigated dose range is additive. This gives
      the freedom and need to select the appropriate dosing ratio of alfentanil and
      propofol by other considerations.

PMID- 12790208
TI  - Modelling the pharmacodynamic interaction between remifentanil and propofol by
      EEG-controlled dosing.
AB  - BACKGROUND AND OBJECTIVE: Knowledge of the pharmacodynamic interaction between
      remifentanil and propofol is important to permit optimal dosage strategies. We
      studied this pharmacodynamic interaction using the median power frequency of the
      processed electroencephalogram as a control parameter for feedback-controlled
      dosing of propofol. METHODS: Twenty-one patients were given total intravenous
      anaesthesia with remifentanil and propofol. During three target-controlled
      infusion regimens, the target concentrations of remifentanil (5, 10, 15 ng mL(
      1)) and propofol dosing were automatically adjusted to keep the median power
      frequency in the range 2 +/- 0.5 Hz. In each patient and during each remifentanil
      target concentration, four arterial propofol/remifentanil concentration pairs
      were measured. The type of interaction was tested using the relative distance
      from the line of additivity and the isobole was modelled using Bernstein splines.
      RESULTS: The results from 13 patients were used for data analysis. The measured
      remifentanil concentrations during the three targets were (mean +/- SD): 3.6 +/-
      0.9, 8.1 +/- 2.5 and 12.4 +/- 2.8 ng mL(-1). The corresponding propofol
      concentrations were 2.64 +/- 0.86, 2.13 +/- 0.58 and 2.09 +/- 0.58 microg mL(-1).
      The data were best described with an additive type of interaction and the isobole
      was estimated using: ((c)Remifentanil/64.2 ng mL(-1)) + ((c)Propofol/2.61 microg
      mL(-1)) = 1. CONCLUSIONS: Within the studied concentration range, remifentanil
      and propofol showed an additive type of pharmacodynamic interaction on the
      electroencephalogram.

PMID- 12790209
TI  - Effect of sevoflurane on the ex vivo secretion of TNF-alpha during and after
      coronary artery bypass surgery.
AB  - BACKGROUND AND OBJECTIVE: Sevoflurane has been used for the induction and
      maintenance of anaesthesia during cardiac surgery owing to its favourable
      haemodynamic effects. It has been suggested that it offers protection against
      myocardial ischaemia-reperfusion injury. METHODS: We investigated the effect of
      sevoflurane on plasma concentrations of tumour necrosis factor-alpha (TNF-alpha)
      after ex vivo stimulation of whole-blood leukocytes by lipopolysaccharide from 20
      patients undergoing coronary artery bypass surgery. The patients were randomized
      to two groups. Group 1 patients were induced and maintained with sevoflurane;
      those in Group 2 were anaesthetized with moderate doses of midazolam-sufentanil.
      Blood samples were drawn from the patients on seven occasions from before
      induction of anaesthesia until 24 h after skin closure. RESULTS: Plasma
      concentrations of TNF-alpha were lower in Group 1 than in Group 2 after cessation
      of cardiopulmonary bypass (median (interquartiles): 25 (21-30) versus 37 (28-79)
      pg mL(-1); P < 0.05) and 24h after skin closure (196 (100-355) versus 382 (233
      718) pg mL(-1); P < 0.05). Postoperatively, two cases of myocardial infarction
      were recorded, one in each group. Six patients in Group 2 needed continued
      inotropic support after the first morning to maintain haemodynamic stability
      versus one patient in Group 1 (P < 0.05). The length of stay in the intensive
      care unit was significantly lower in Group 1 than in Group 2 (mean +/- SD: 25 +/-
      16 versus 54 +/- 30 h; P < 0.05). CONCLUSIONS: Sevoflurane reduces production of
      TNF-alpha more than total intravenous anaesthesia with midazolam-sufentanil
      during cardiac surgery. This may reduce cardiac morbidity and the length of stay
      in the intensive care unit.

PMID- 12790210
TI  - Pharmacokinetic-based total intravenous anaesthesia using remifentanil and
      propofol for surgical myocardial revascularization.
AB  - BACKGROUND AND OBJECTIVE: We investigated the following aspects of
      pharmacokinetic-guided total intravenous anaesthesia with remifentanil and
      propofol in patients undergoing surgical myocardial revascularization:
      anaesthetic efficacy, haemodynamic effects, impact on extubation of the trachea
      and analgesia after operation. METHODS: Thirty-two patients undergoing on-pump
      coronary bypass surgery received intravenous anaesthesia with remifentanil and
      propofol. Both drugs were dosed and titrated based on computer-assisted
      pharmacokinetic models to maintain constant plasma concentrations. The propofol
      target plasma concentration was 1.2 microg mL(-1) throughout the procedure. A
      remifentanil target plasma concentration of 8 ng mL(-1) was achieved over 2 min
      for induction. After tracheal intubation, the opioid plasma concentration was
      reduced to 4 ng mL(-1), and then titrated up to 8 ng mL(-1) during surgery.
      Postoperative analgesia was managed with remifentanil infusion until 4 h after
      tracheal extubation, and a continuous infusion of tramadol was started 1 h before
      the remifentanil was stopped. RESULTS: After induction of anaesthesia, heart rate
      (-20%) and cardiac index (-6%) decreased significantly. No hypotensive episodes
      (mean arterial pressure < 60 mmHg) occurred. Intraoperative haemodynamics were
      stable. Three cases of myocardial ischaemia were detected: two by
      transoesophageal echocardiography and one with ST-segment monitoring. The
      duration of postoperative mechanical ventilation of the lungs was 95 +/- 13 min
      and the time to extubation was 150 +/- 18 min. Postoperative analgesia was
      satisfactory in all patients. CONCLUSIONS: Pharmacokinetic-based total
      intravenous anaesthesia with remifentanil and propofol provides adequate
      anaesthesia during coronary surgery with cardiopulmonary bypass and allows safe
      early extubation after operation.

PMID- 12790211
TI  - Changes in gas concentrations in the Brandt endotracheal tube cuff during and
      after anaesthesia with nitrous oxide.
AB  - BACKGROUND AND OBJECTIVE: The mechanism underlying stable cuff pressure in the
      Brandt rediffusion endotracheal tube during anaesthesia with nitrous oxide is not
      fully understood. The present study assessed changes in gas concentrations in the
      cuff during and after nitrous oxide anaesthesia. METHODS: The pressure of an air
      filled Brandt endotracheal tube cuff was measured; anaesthesia was maintained
      with nitrous oxide 67% and oxygen 33% for 6 h in the Continuous Group; oxygen was
      substituted for nitrous oxide after 3 h of nitrous oxide anaesthesia in the
      Discontinuous Group (n = 8 for each). In some other patients, the study was
      terminated at 90, 180, 270 and 360 min (n = 8 for each). Gas concentrations in
      the cuff were measured at the end of the study. RESULTS: Cuff pressures increased
      slightly during the first 180 min of anaesthesia (P < 0.001). Thereafter, the
      cuff pressure did not change significantly in the Control Group but decreased in
      the Discontinuous Group (P < 0.001); there was a significant difference between
      the two groups (P < 0.0001). Cuff pressure never exceeded 22 mmHg and there were
      no air leaks in either group during the 6 h anaesthesia. Nitrous oxide
      concentrations in the cuff were 11.3 +/- 2.6% and 2.6 +/- 0.8% in the Control
      Group and Discontinuous Groups, respectively; however, changes in carbon dioxide
      and oxygen concentrations in the cuff were within approximately 1%. CONCLUSIONS:
      Small changes in the nitrous oxide concentration in the cuff contribute to a
      stable cuff pressure in the Brandt rediffusion system, but changes in carbon
      dioxide or oxygen concentrations have little effect.

PMID- 12790212
TI  - Effect of bispectral index monitoring on sevoflurane consumption.
AB  - BACKGROUND AND OBJECTIVE: The bispectral index, a parameter derived from the
      electroencephalograph, has been shown to correlate with the loss of consciousness
      and sedation. This study was designed to assess the effects of bispectral index
      monitoring on sevoflurane and its recovery profiles. METHODS: Sixty ASA I and II
      patients undergoing open abdominal surgery were randomized into two groups: one
      monitored using the bispectral index (Group BIS) and the other without its use
      (controls). After a standardized induction, anaesthesia was maintained with
      sevoflurane in both groups. In Group BIS, sevoflurane was titrated to maintain
      the bispectral index in the range 40-60. In the control group, the administered
      sevoflurane concentration was adjusted according to the signs of anaesthesia. The
      end-tidal sevoflurane concentration, bispectral index and routine haemodynamic
      variables were noted every 5 min during surgery. The consumption of sevoflurane
      was computed. At the conclusion of surgery operations, the time to 'open eyes on
      verbal command', 'motor response to verbal command' and Aldrete's score were
      recorded by a blinded anaesthesiologist. RESULTS: The difference in the
      consumption of sevoflurane was not significant between the groups. Bispectral
      index monitoring was associated with a reduction of 4.73% in sevoflurane usage
      and 2.19 mL h(-1) was saved. CONCLUSIONS: Bispectral index monitoring during
      anaesthesia provides only a small advantage related to the need to monitor the
      depth of anaesthesia.

PMID- 12790213
TI  - Perioperative headache and day case surgery.
AB  - BACKGROUND AND OBJECTIVE: Headache is a common and distressing morbidity
      associated with day case surgery. We undertook a prospective, observational study
      to identify risk factors associated with perioperative headache in a modern, day
      case surgery setting. METHODS: Two hundred-and-thirty consecutive patients
      presenting for day case surgery were invited to complete a questionnaire about
      their previous experience of headache and various associated risk factors.
      Questionnaires were completed by 90% of patients. The presence of headache in the
      pre- or postoperative period was also documented. We used multivariate logistic
      regression to model perioperative headache. RESULTS: Increased frequency of
      previous headache, odds ratio (95% confidence interval) 1.9 (1.2-2.8) (P = 0.004)
      and low alcohol consumption 0.90 (0.87-0.98) (P = 0.019) were significant
      predictors. A history of migraine showed a trend towards being predictive 1.9
      (0.9-4.0) (P = 0.055). Some risk factors thought to be important such as caffeine
      withdrawal and duration of starvation and fluid deprivation were not associated
      with perioperative headache in this setting. CONCLUSIONS: In this study of risk
      factors associated with perioperative headache in day case surgery, increased
      frequency of headache and low alcohol consumption were independent risk factors.

PMID- 12790214
TI  - Analgesic effects of intrathecal neostigmine in perianal surgery.
AB  - BACKGROUND AND OBJECTIVE: In recent human and animal studies, intrathecal
      administration of various doses of neostigmine produces analgesia without
      neurotoxicity. The aim was to examine the effects of intrathecal neostigmine and
      bupivacaine in patients undergoing perianal surgery under spinal anaesthesia.
      METHODS: The patients were randomly allocated into three groups of 15: Group 1
      (controls) received hyperbaric bupivacaine 10 mg + dextrose 5%, 1 mL, to a total
      volume of 3 mL; Group 2 received hyperbaric bupivacaine 10 mg + neostigmine 25
      microg in dextrose 5%, 1 mL, to a total volume of 3 mL; and Group 3 received
      hyperbaric bupivacaine 10 mg + neostigmine 50 microg in dextrose 5%, 1 mL, to a
      total volume of 3 mL. RESULTS: The onset of sensory block was significantly
      earlier for Group 2 and 3 patients compared with Group 1 patients (P < 0.05). The
      full time to recovery of motor block and sensory block was significantly longer
      in Group 3 compared with Group 1 (P < 0.05). In Group 3, the average time until
      the first dose of tramadol was longer than Group 1 (P < 0.05). The incidence rate
      of nausea and vomiting was significantly higher in Groups 2 and 3 than in Group 1
      (P < 0.05). CONCLUSIONS: The use of intrathecal neostigmine as an analgesic drug
      in perianal surgery is unsatisfactory because of prolonged motor blockade and
      nausea.

PMID- 12790215
TI  - Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction
      injury rat model.
AB  - BACKGROUND AND OBJECTIVE: Trazodone hydrochloride is used in the treatment of
      neuropathic pain. However, the analgesic effects of trazodone on neuropathic pain
      are controversial. The study was undertaken to determine the analgesic effect of
      trazodone on a chronic constriction injury model. METHODS: We tested the effect
      of trazodone on thermal hyperalgesia due to a chronic constriction injury of the
      sciatic nerve in rats and examined the effects of lesions in the descending and
      ascending serotonergic system induced by 5,7-dihydroxytriptamine (5,7-DHT).
      RESULTS: The analgesic effects of trazodone showed a clear dose dependency.
      Furthermore, the analgesic effect of trazodone was observed in rats injected with
      5,7-DHT into the dorsal raphe nucleus and medial raphe nucleus. CONCLUSIONS: The
      results suggest that a mainly serotonergic descending pain control pathway
      mediates the analgesic effects of trazodone.

PMID- 12790216
TI  - Postoperative pain management with intravenous patient-controlled morphine:
      comparison of the effect of adding magnesium or ketamine.
AB  - BACKGROUND AND OBJECTIVE: This double-blind randomized study tested whether the
      addition of magnesium or ketamine to morphine for intravenous patient-controlled
      analgesia resulted in improved analgesic efficacy and lower pain scores compared
      with morphine patient-controlled analgesia alone after major abdominal surgery.
      METHOD: Ninety patients (3 x 30) were randomly allocated to receive either
      morphine 0.4 mg mL(-1) (Group M) by patient-controlled analgesia, morphine 0.4mg
      mL(-1) + MgSO4 30mg mL(-1) (Group MM) or morphine 0.4 mg mL(-1) + ketamine 1 mg
      mL(-1) (Group MK). Postoperative analgesia was started when the verbal rating
      scale was > or = 2. Patients were first given a standardized loading dose (0.05
      mg kg(-1)) of the study solution. They were then allowed to use bolus doses of
      this solution (0.0125 mg kg(-1) every 20 min without time limit). Discomfort,
      sedation, pain scores, cumulative morphine consumption and adverse effects were
      recorded up to 24 h after the start of the patient-controlled analgesia. RESULTS:
      The level of discomfort, level of sedation and verbal rating scores decreased
      significantly with time in all groups (P < 0.05). Both verbal rating and
      discomfort scores were significantly lower in Groups MM and MK at 15, 30 and 60
      min compared with Group M (P < 0.001). Cumulative morphine consumption after 12
      and 24 h was significantly higher in Group M alone (median 26 and 49 mg,
      respectively) compared with Group MM (24.2 and 45.7 mg) and Group MK (24.4 and
      46.5 mg). CONCLUSIONS: In the immediate postoperative period, the addition of
      magnesium or ketamine to morphine for intravenous patient-controlled analgesia
      led to a significantly lower consumption of morphine. However, these differences
      are unlikely to be of any clinical relevance.

PMID- 12790217
TI  - Acid-base management during hypothermic neuroprotection.

PMID- 12790218
TI  - Egg membrane as a new biological dressing in split-thickness skin graft donor
      sites: a preliminary clinical evaluation.
AB  - BACKGROUND: This preliminary investigation attempted to determine the
      effectiveness of egg membranes as a new biological dressing to promote infection
      free healing and provide pain relief over split-thickness skin graft (STSG) donor
      sites. METHODS: Eighteen patients, with 28 STSG donor sites who were admitted to
      the LinKou Burn Center from August 1997 to July 1999, were selected for this
      trial. The bilateral thighs were the main donor sites for STSG. To compare
      different dressings, Surgilon, B.G.C. (beta-glucan collagen), and Biobrane were
      applied to the same donor sites, and epithelialization, pain relief, fluid
      accumulation, hematoma formation, and the occurrence of rejection or infection
      were monitored post-application. RESULTS: The average wound healing time with egg
      membrane application was 11.64 +/- 1.29 (range, 10 to 13) days. Meanwhile, the
      average wound healing times for B.G.C. (6 patients) and Biobrane (6 patients)
      were 14.5 +/- 0.84 and 14.0 +/- 0.63 days, respectively. Finally, Surgilon (16
      patients) had the longest healing time, at 16 +/- 1.41 days. On average, complete
      pain relief was achieved by 7.3 +/- 0.70 days for egg membrane application, while
      for B.G.C., Biobrane, and Surgilon, complete pain relief occurred by 7.0 +/-
      0.89, 6.0 +/- 0.63, and 10.0 +/- 0.37 days, respectively. Finally, no infection
      or rejection developed during healing. CONCLUSIONS: From this preliminary study,
      egg membrane may be an ideal STSG donor site dressing, as it possesses properties
      of pain relief, wound protection, promotion of healing, and low cost. However,
      the limited unit size must be overcome, and its clinical application for burn
      wounds should be studied.

PMID- 12790219
TI  - Surgical correction of postradiation spinal deformity.
AB  - BACKGROUND: Radiation to the juxtaspinal area in children with malignant tumors
      induces the appearance of a postradiation spinal deformity (PRSD) with drastic
      progression during the growth spurt, so surgical correction is mandatory. Methods
      of surgical treatment depend on the age of the patient, and the type and size of
      the spinal deformity. METHODS: A long-term retrospective survey of 6 patients
      receiving surgical management of kyphoscoliosis was conducted. The original
      tumors were 3 Wilms' tumors, 2 neuroblastomas, and 1 lymphoma. The mean length of
      time for tumor excision and subsequent radiation was 2.2 years. The total
      radiation dose averaged 3566 rad. The mean age at initial presentation was 6.1
      years and that at spinal correction was 11.8 years. Single posterior surgery was
      performed in 3 cases, while the other 3 required anteroposterior correction due
      to severe deformity and scar contracture. RESULTS: The curves of PRSD were
      concave toward the side irradiated, and the kyphotic component was more severely
      involved than was the scoliotic component. Four patients had favorable correction
      without curve progression. However, in the other 2 younger patients, due to
      thinness of their back, rigid angulation of the spine, poor bony stock, and
      medical comorbidity, spinal instrumentation was rather difficult. Postoperative
      pseudarthrosis and subsequent rod protrusion occurred with progressive kyphosis.
      CONCLUSIONS: PRSDs consist of uncommon developmental vertebral anomalies, of
      which curved patterns occur in any combination, but most severely involve the
      presence of collapsing kyphosis and soft tissue contracture. Surgical correction
      may be less effective, especially if the children are skinny and have low bone
      stocks.

PMID- 12790220
TI  - Clinical results of a single central interbody fusion cage and transpedicle
      screws fixation for recurrent herniated lumbar disc and low-grade
      spondylolisthesis.
AB  - BACKGROUND: The posterior lumbar interbody fusion (PLIF) procedure allows
      restoration of the weight-bearing capacity to a more physiological ventral
      position and maintenance of disc space height. However, the procedure can be
      technically difficult and may cause complications. It has always been performed
      bilaterally with paired cages; a single central cage has not been commonly used.
      METHODS: Twenty-eight patients who met the interbody fusion criteria from March
      1999 through November 2001 were included in the study. Surgery was performed from
      the posterior with a single central cage supplemented with transpedicle screws.
      The follow-up period ranged from 8 to 39 months with a mean of 14.4 months.
      Clinical outcomes were assessed. Dynamic radiography for fusion mass was
      interpreted by an independent radiologist. RESULTS: Overall, 92.86% of the
      patients were satisfied with their conditions after surgery. Radiography study
      showed the rate of bony fusion being 82.14%. Fibrous union was noted in five
      patients. No migration of the cage was observed. One patient experienced
      laceration of the dura without clinical sequelae. One patient had transient
      paresthesia and recovered within 2 weeks. One patient had transient bladder atony
      and recovered within 3 days. Overall, the complications were negligible and none
      of the patients sustained a motor deficit and permanent complication.
      CONCLUSIONS: The PLIF procedure using a single, central cage combined with
      bilateral pedicle screws fixation obtained satisfactory outcome within a short
      term or long-term follow-up period. Since the implant-related complications have
      seldom been observed, it may be used as an alternative option for recurrent
      lumbar disc herniation or low grade spondylolisthesis with apparent degenerative
      disc disease.

PMID- 12790221
TI  - Initial experience during balloon angioplasty assisted surgical thrombectomy for
      thrombosed hemodialysis grafts.
AB  - BACKGROUND: Access failure in hemodialysis patients is commonly encountered by
      vascular surgeons. Researchers have reported various solutions for dealing with
      clotted grafts, including thrombectomy, thrombolysis, interposition grafting,
      angioplasty, or a combination of these methods. Surgical thrombectomy has been
      the standard procedure for dealing with thrombosed hemodialysis grafts in the
      cardiovascular department of Chang Gung Memorial Hospital. However, to correct
      associated stenotic lesions and improve the results of surgery, intraoperative
      balloon angioplasty has been applied in consecutive cases of dialysis graft
      failure since July 2001. METHODS: Initial experience with 13 consecutive
      intraoperative balloon angioplasties performed during a 2-month period was
      reviewed. Noncompliant high-pressure balloons were used for the procedures. Age,
      gender, graft age, and initial outcome were reviewed and analyzed. RESULTS: A
      success rate of 100% was achieved in the group that underwent thrombectomy plus
      intraoperative balloon angioplasty. Furthermore, the primary potency rates were
      77% at 1 month, 62% at 3 months, and 38% at 6 months. CONCLUSIONS: We recommend
      intraoperative balloon angioplasty plus surgical thrombectomy as an effective
      method of salvaging thrombosed hemodialysis grafts. However, since these are the
      initial results for this kind of hybrid procedure from a single hospital, large
      scale studies with long-term follow up are required.

PMID- 12790222
TI  - A survey of the oral status of children undergoing liver transplantation.
AB  - BACKGROUND: The purposes of this study were to examine the oral tissues and
      caries prevalence of children undergoing liver transplantation, and to evaluate
      the relationship between tooth staining and serum bilirubin level. METHODS:
      Thirty-four children (22 boys and 12 girls) under the age of 6 years with end
      stage liver disease were referred from the Liver Transplantation Center at
      Kaohsiung Chang Gung Children's Hospital, Taiwan. Oral tissues were examined, and
      photographs taken to determine the green staining of the teeth and gingiva. A
      questionnaire was completed by their parents. Serum bilirubin levels were
      collected preoperatively in these children. Student's t-test was used to compare
      the mean decayed, missing, and filled tooth (dmft) difference between night-fed
      and non-night-fed groups, and to test the relationships between tooth staining
      and serum bilirubin levels. RESULTS: The caries prevalence of the 34 children
      undergoing liver transplantation was 61.8%. The mean dmft score of children 2 to
      6 years old who were night-fed was significantly higher than that of children who
      were not (10.1 +/- 1.2 vs. 6.3 +/- 1.2; p = 0.038). Green staining of the teeth
      and gingiva was found in 61.3% of cases in children with biliary atresia. Total
      serum bilirubin levels were significantly higher in the green-stained group than
      in the non-stained group (17.87 +/- 2.50 vs. 2.20 0.65; p < 0.01). CONCLUSIONS:
      Oral findings of children undergoing liver transplant presented significant green
      staining of the teeth and gingiva related to high serum bilirubin levels.
      Children who were night-fed showed an increased risk of developing caries
      suggesting that oral hygiene instructions should begin as early as possible
      before liver transplantation.

PMID- 12790223
TI  - Vascular injury during a lumbar laminectomy.
AB  - A lumbar laminectomy is a common and routine operation. Damage to abdominal
      vascular structures during surgery is a relatively infrequent complication;
      however, when it does occur, it is sudden and life-threatening. We herein report
      on 2 cases of abdominal vascular injury which occurred during lumbar
      microdiscectomies. The first case was a 34-year-old man. A bloody surgical field
      was noted 45 min into the operation along with an increase in heart rate and a
      decrease in blood pressure. After fluid resuscitation and an ephedrine injection,
      his vital signs stabilized. The patient was then sent to the surgical intensive
      care unit for observation. An emergent abdominal computer tomography scan
      revealed right retroperitoneal hematoma, and an urgent exploratory laparotomy was
      performed to check for bleeding and to remove the hematoma. The second case was a
      61-year-old woman with recurrent disc herniation. The operation was proceeding
      smoothly for 90 min, when a large amount of fresh blood suddenly gushed out. Her
      blood pressure immediately dropped to that of a state of shock. The patient was
      turned back to a supine position, and an emergent laparotomy was done to repair
      the injured vessels. Both patients had uneventful recoveries.

PMID- 12790224
TI  - Severe portopulmonary hypertension in congenital hepatic fibrosis.
AB  - Portopulmonary hypertension is a rare complication of portal hypertension.
      Although epoprostenol infusion, nitric oxide inhalation, isosorbide-5
      mononitrate, nitroglycerin, and calcium channel blockers may reduce pulmonary
      artery pressure in patients with portopulmonary hypertension, the prognosis
      remains poor. We present a case of congenital hepatic fibrosis associated with
      pulmonary hypertension. A 42-year-old man with congenital hepatic fibrosis
      visited our hospital with syncope. The man had suffered from breathlessness on
      exertion for 2 weeks before the episode of syncope. He also had a history of
      portal hypertension with documented gastric cardiac varices at the age of 28
      years. Despite undergoing intensive care, the patient died 1 week after admission
      owing to severe right-sided heart failure. Autopsy revealed dilatation of the
      right atrium and right ventricle grossly and plexogenic pulmonary arteriopathy
      microscopically. Accurate diagnosis of portopulmonary hypertension requires
      awareness of the disease and a high index of suspicion when examining patients
      with portal hypertension and dyspnea.

PMID- 12790225
TI  - Alternate-sided homonymous hemianopia as the solitary presentation of
      mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes syndrome.
AB  - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) syndrome has various presentations. We report on a case of MELAS in which
      alternate-sided homonymous hemianopia was the main symptom of recurrent
      neurological defects. A 19-year-old woman suffered from blurred vision,
      headaches, vomiting, and fever that subsided within days. The ophthalmic
      examination demonstrated right homonymous hemianopia. One month later a similar
      episode occurred again. Computed tomography (CT) and magnetic resonance imaging
      (MRI) of her brain revealed an infarct in the left temporo-occipital lobes.
      Exercise tests showed lactic acidosis, and a muscle biopsy confirmed the
      diagnosis of mitochondrial myopathy. Half a month later, a third episode
      occurred. Visual field examination demonstrated left homonymous hemianopia and
      partial recovery of the right visual field. The infarct in the brain, as revealed
      by CT and MRI, was compatible with the visual field changes. MELAS should be
      ruled out in young patients who present with homonymous hemianopia accompanied by
      recurrent headaches or other recurrent symptoms.

PMID- 12790226
TI  - Adenocarcinoma of the jejunum: a pediatric case report.
AB  - The clinical history and surgical findings of an adenocarcinoma of the jejunum in
      a 15-year-old boy are reported. The diagnosis of small bowel carcinoma remains
      difficult, primarily because of the rarity of the disease and the ambiguity of
      its symptoms. We reviewed the literature on this subject and found a total of
      seven cases of adenocarcinima of the jejunum and ileum in patients under 20 years
      of age. We report this case for its rarity and the findings which should alert
      the pediatricians including intermittent abdominal pain, severe loss of body
      weight, and stools positive for guaiac.

PMID- 12790227
TI  - Synovial chondromatosis of the hip: management with arthroscope-assisted
      synovectomy and removal of loose bodies: report of two cases.
AB  - Primary synovial chondromatosis is an uncommon disorder, and involvement of the
      hip joint is rare. The clinical symptoms are usually non-specific, and a clinical
      diagnosis of synovial chondromatosis of the hip may be difficult and delayed,
      especially before the ossifying nodules become evident. Loose bodies in the joint
      can cause secondary degenerative osteoarthritis of the hip. Currently, the
      recommended management is surgical removal of the loose bodies and a synovectomy
      without dislocation of the hip joint. Herein we report on 2 cases of synovial
      chondromatosis of the hip, which were managed with an arthroscope-assisted
      synovectomy and removal of the loose bodies. We believe this is an easy and safe
      method for management of this disorder.

PMID- 12790228
TI  - Children with ectodermal dysplasia need early treatment.

PMID- 12790229
TI  - Oral hygiene, gingivitis, and periodontitis in persons with Down syndrome.
AB  - This study was conducted to determine and compare the prevalence, severity, and
      extent of gingivitis and periodontitis in patients with Down syndrome and
      patients who did not have Down syndrome. The authors also assessed the
      relationship of these conditions and compared them to the age, gender, and oral
      hygiene profiles in both groups. Using a case-control study design, the authors
      examined 32 individuals with Down syndrome (DS) and matched each with a
      participant from the control group (CG) according to age and gender. Researchers
      determined the Simplified Oral Hygiene Index, Gingival Index, and measured the
      level of gingival attachment for each participant. The authors found that the
      relationship between the presence of dental plaque and the severity of gingivitis
      was moderate among participants with DS. While the overall characteristics of the
      periodontal and gingival health status were not markedly different between the
      two groups, the extent and severity of gingivitis and the extent of periodontitis
      were greater in the group with DS than in the CG.

PMID- 12790230
TI  - Evaluation of health questionnaires used in dentistry.
AB  - An evaluation of a patient's general health before dental treatment is necessary
      to identify any systemic conditions, which may influence treatment and allow the
      dentist to evaluate risks, and reduce possible complications. Of the 860 dentists
      contacted by mail, 112 provided health questionnaires used in their offices. The
      authors evaluated the information in these questionnaires by describing content
      and rating them according to the importance of each topic. Questions were divided
      into categories and compared against a standard list of health-related topics.
      The authors also assessed the questionnaires based on dentists' area of
      specialization and length of clinical experience. It was not possible to
      establish a statistically significant correlation between the quality of a health
      questionnaire and dentists' specialty or length of experience; however, the
      questionnaires used by periodontists were rated as more comprehensive than those
      adopted by pedodontists (p < 0.05). Overall, the topics asked about most
      frequently were allergies, diabetes, and patient drug use.

PMID- 12790231
TI  - Stimulated whole saliva components in children with Down syndrome.
AB  - The authors report on the components of stimulated whole saliva from children
      with Down syndrome--including pH, flow rate, sialic acid and protein
      concentrations, and amylase and peroxidase activity. Saliva samples were
      collected from 35 children aged 6-10 years. Of the participants, 17 had Down
      syndrome and 18 did not. To stimulate saliva production, the children chewed a
      piece of parafilm for 10 minutes before the sample was collected. Soon after
      collecting the saliva sample, the authors measured pH using a portable pH-meter.
      Sialic acid levels were determined with a thiobarbituric acid assay. Protein
      content was determined with Folin's phenol reagent. Amylase was assayed and the
      authors measured the maltose produced by the breakdown of starch and peroxidase
      using orthodianisidine. No statistically significant difference was observed in
      levels of sialic acid (free and total) between the two groups. Protein
      concentration was about 36% higher in the group with Down syndrome. However, the
      salivary flow rate, pH, and amylase and peroxidase activities were lower among
      the children with Down syndrome.

PMID- 12790232
TI  - Dental findings in 4-, 14-, and 25-to 35-year-old Hong Kong residents with mental
      and physical disabilities.
AB  - This study was designed to collect baseline data on dental status of 4-, 14- and
      25- to 35-year-old Hong Kong residents who were mentally impaired and physically
      disabled. Participants were randomly selected from figures derived from a pilot
      survey, and dentally examined. The mean dmft/DMFT scores were 1.25, 2.27, and
      5.23 (Missing component of 3.02), respectively. There was no correlation between
      caries experience and physical mobility, mental impairment, or sex in any age
      group. No visible plaque was found in 85.1% of 4 year olds (n = 309), 52.3% 14
      year olds (n = 174), and 36.2% 25 to 35 year olds (n = 264). Visible plaque was
      recorded for 13.6% 4 year olds, 30.5% 14 year olds, and 47% 25 to 35 year olds.
      Abundant plaque was detected in 1.4% 4 year olds, 17.2% 14 year olds, and 15.8%
      25 to 35 year olds. No calculus was observed in the 4 year olds, but 20.2% of 14
      year olds had calculus as did 56.3% of the 25 to 35 year olds.

PMID- 12790233
TI  - Use of participatory epidemiology in studies of the persistence of lineage 2
      rinderpest virus in East Africa.
AB  - In 1994, rinderpest virus of African lineage 2 was detected in East Africa after
      an apparent absence of more than 30 years. In 1996, a disease search, based on
      participatory epidemiological techniques supplemented by serological and
      virological analyses, was undertaken in southern Somalia and north-eastern Kenya
      to collate past and current epidemiological information about rinderpest
      compatible disease events, and to test the hypothesis that African lineage 2
      rinderpest virus persists in populations of transhumant cattle in the Somali
      ethnic areas. The findings in Afmadu in Lower Juba led the search for rinderpest
      to the communities in the Bardera area and then on to the Kenya/Somalia border
      areas between Mandera and El Wak. The herders had a specific knowledge of the
      clinical signs of rinderpest and provided detailed and accurate descriptions of
      cases. They differentiated between classical acute rinderpest and a milder
      syndrome characterised by an ocular discharge and diarrhoea, few oral lesions,
      corneal opacity and occasional mortality. The studies provided evidence for the
      endemic occurrence of rinderpest back to at least 1981, with a periodicity of
      five years in the incidence of the disease. After a period of high mortality in
      1992 to 1993, around Afmadu, herders reported a mild disease, with occasional
      increases in mortality, from other areas of Lower Juba and the Gedo Region.
      Reports by herders of a rinderpest-compatible disease in the El Wak area were
      pursued until active cases were located and rinderpest was confirmed.

PMID- 12790234
TI  - Multifocal eosinophilic enteritis associated with a small intestinal obstruction
      in a standardbred horse.
AB  - A seven-year-old standardbred gelding developed marked signs of colic associated
      with an acute small intestinal obstruction. Surgical exploration revealed three
      intramural, circumferential constricting lesions in the small intestine, the two
      most severe of which were in the jejunum and were resected. The horse was
      euthanased owing to postoperative complications. Histopathological examination
      confirmed the diagnosis of idiopathic multifocal eosinophilic enteritis.

PMID- 12790235
TI  - Control of cutaneous mycosis in five chimpanzees (Pan troglodytes) with
      lufenuron.
AB  - Five chimpanzees at the Limbe Wildlife Centre in Cameroon, of both sexes and
      between six and eight years of age, were treated with lufenuron at a dose rate of
      60 mg/kg bodyweight to control various types of mycotic skin infections. The
      409.8 mg tablets were administered by mixing them with milk and avocado. Each
      animal received two or three treatments three weeks apart. Most of them improved
      significantly during the two to three weeks after the first treatment, and they
      had completely recovered two to four months later. All the chimpanzees accepted
      the medication readily, and no adverse drug reactions were observed either
      immediately after the treatment or during the subsequent eight to 10 months.

PMID- 12790236
TI  - Rapid screening of chicken intestinal contents for Campylobacter jejuni using
      coagglutination.

PMID- 12790237
TI  - Lingual squamous cell carcinoma in an ocelot (Felix pardalis).

PMID- 12790238
TI  - Non-fatal aflatoxicosis in Arabian horses in Iraq.

PMID- 12790240
TI  - Thoracic intervertebral disc protrusion in a donkey.

PMID- 12790241
TI  - Ethics of kidney transplants in cats and dogs.

PMID- 12790239
TI  - Bovine herpesvirus type 5 in the semen of a bull not exhibiting clinical signs.

PMID- 12790242
TI  - Veterinary surveillance.

PMID- 12790243
TI  - Veterinary surveillance.

PMID- 12790244
TI  - Crushed tail head syndrome in cattle.

PMID- 12790245
TI  - Anal biting in pigs.

PMID- 12790246
TI  - Contagious ovine digital dermatitis.

PMID- 12790247
TI  - Supply of POMs.

PMID- 12790248
TI  - Dressing down.

PMID- 12790249
TI  - Cats with allergic skin disease.

PMID- 12790250
TI  - Biased cognitive processing of cancer-related information among women with family
      histories of breast cancer: evidence from a cancer stroop task.
AB  - Stimuli associated with sources of stress have been shown to interfere with
      cognition. The authors hypothesized that women with the stress of having a family
      history of breast cancer (FH+) would exhibit greater interference on a task with
      cancer-related stimuli than women without cancer in the family (FH-). The authors
      developed a modified Stroop color-naming task to test this hypothesis in a sample
      of FH+ (n = 72) and FH- (n = 96) women. Consistent with the hypotheses, FH+ women
      had longer color-naming times and more errors (ps < .01) on a cancer word list
      relative to noncancer lists. This biased processing was not mediated by the
      significantly higher perceived risk, general distress, or cancer-specific
      distress in FH+ women. Maladaptive alterations in processing cancer stimuli may
      have important clinical implications, as these women must process complex cancer
      related information critical to their health (e.g., options for chemoprevention,
      screening).

PMID- 12790252
TI  - Effect of valued activity disability, social comparisons, and satisfaction with
      ability on depressive symptoms in rheumatoid arthritis.
AB  - This longitudinal study identified a model through which function affects the
      psychologicalwell-being of individuals with rheumatoid arthritis (RA). Results of
      hierarchical linear regression analyses (N = 436) demonstrated that greater
      physical impairment resulted in greater disability in valued activities and
      engagement in unfavorable social comparisons. All 3 factors--greater physical
      impairment, greater disability in valued activities, and unfavorable comparison
      evaluations--predicted low satisfaction with abilities. Low satisfaction with
      abilities was the most important predictor of higher depressive symptoms and
      mediated the impact of physical impairment, valued activity disability, and
      unfavorable comparisons on depressive symptoms. Results highlight the role of
      personal meaning attached to changes in functional status in predicting the long
      term psychological well-being of individuals with chronic illnesses such as RA.

PMID- 12790251
TI  - A population study of low-rate smokers: quitting history and instability over
      time.
AB  - This study used 1 longitudinal and 2 cross-seconal population surveys to compare
      stability of low-rate daily smokers (less than 5 cigarettes per day) with other
      daily smokers and occasional smokers. Few low-rate smokers maintained consumption
      level; 36% retained smoking status after 20 months, compared with 82% and 44% for
      regular daily and occasional smokers, respectively. In a dynamic process,
      established smokers quit smoking and/or modified (decreased or increased)
      consumption. Low-rate and occasional smokers quit at higher rates than regular
      daily smokers (odds ratios 3:1) but were replenished by new members, many
      converted from regular daily smoker. The overall trend is an increasing
      proportion of low-consumption smokers while smoking prevalence declines. The
      dynamic process has implications for tobacco control efforts and for addiction
      theory.

PMID- 12790254
TI  - Conflict structure moderates associations between cardiovascular reactivity and
      negative marital interaction.
AB  - This study examined the role of marital conflict structure--who desires and
      requests change versus who responds to the change request--in spouses'
      cardiovascular responses to marital interactions. Forty-one couples discussed 2
      marital topics: one in which the wife desired change in the husband, and one in
      wich the husband desired change in the wife. Cardiovascular responses were
      assessed at 2-min intervals. Results indicated that marital conflict structure
      moderates cardiovascular reactivity during negative marital interactions:
      Husbands and wives whose interactions were characterized by high levels of
      negative behavior showed the most pronounced diastolic blood pressure reactivity,
      but only when they were in the role of desiring change in their spouses.
      Implications for gender difference in marital conflict physiology are considered.

PMID- 12790253
TI  - Memory in pediatric patients undergoing conscious sedation for aversive medical
      procedures.
AB  - This study investigated preserved memory in 26 pediatric cancer patients (65%
      boys, 77% Caucasian, mean age = 12.5 years) undergoing midazolam-induced
      conscious sedation during painful medical procedures to treat hematological or
      oncological diseases. The sedative midazolam had a significant anterograde
      amnesic effect on participants' performance on a visual recognition (explicit)
      memory task but not on a visual perceptual facilitation (implicit) memory task.
      That implicit memory scores were relatively unaffected while explicit memory
      scores deteriorated significantly indicates that leaning occurred while
      participants were sedated, even when participants did not recollect the learning
      event. These findings, which replicate those of M. R. Polster, R. A. McCarthy, G.
      O'Sullivan, P. A. Gray, and G. R. Park (1993) in a study of adults, have
      implications for the development and treatment of conditioned anxiety reactions
      associated with aversive medical procedures.

PMID- 12790255
TI  - Hostility predicts metabolic syndrome risk factors in children and adolescents.
AB  - The authors tested in 134 African American and European American children whether
      hostility measured at study entry predicted the metabolic syndrome risk factors
      an average of 3 years later. Hostility was measured with the Cook-Medley
      Hostility Scale (W. W. Cook & D. M. Medley, 1954) and with ratings of Potential
      for Hostility from interview responses. Metabolic syndrome was based on having at
      least 2 of the following risk factors above the 75th percentile of scores for
      their age, race, and gender group: body mass index, insulin resistance index,
      ratio of triglycerides to high-density lipoprotein cholesterol, and mean arterial
      blood pressure. Children who exhibited high hostility scores at baseline were
      likely to exhibit the metabolic syndrome at the follow-up. The results highlight
      the potential importance of early prevention and intervention of behavioral risk
      factors for cardiovascular disease.

PMID- 12790256
TI  - Sleeping problems and health behaviors as mediators between organizational
      justice and health.
AB  - The aim of this longitudinal cohort study was to investigate whether sleeping
      problems and health behaviors (smoking, alcohol consumption, and sedentary
      lifestyle) mediate the association between organizational justice and employee
      health. Health indicators were minor psychiatric morbidity, as assessed by the
      General Health Questionnaire (U. Werneke, D. P. Goldberg, I. Yalcin, & B. T.
      Ustun, 2000), and poor self-rated health status. The results of logistic
      regression analysis of data for 416 male and 3,357 female hospital employees
      working during the 1998-2000 period in 10 Finnish hospitals suggest that sleeping
      problems are one of the underlying factors causing the adverse health effects of
      low organizational justice at work. No support for a mediating role of health
      behaviors between low organizational justice and health problems was obtained.

PMID- 12790257
TI  - Spiritual health locus of control and breast cancer beliefs among urban African
      American women.
AB  - The present study examined the relationship between spiritual health locus of
      control, breast cancer beliefs, and mammography utilization among a sample of
      1,227 African American women from urban public health centers. Spiritual health
      locus of control was conceptualized as having an active and passive dimension,
      empowering individuals in their health beliefs and behaviors or rendering them to
      rely on a higher power (e.g., God) to determine their health outcomes,
      respectively. The active dimension was negatively associated with perceived
      benefits of mammography and positively associated with perceived barriers to
      mammography. The active and passive spiritual dimensions are distinct from
      internal and external health locus of control. Further study of their
      associations with other health-related beliefs and behaviors is warranted.

PMID- 12790258
TI  - Chronic stress burden, discrimination, and subclinical carotid artery disease in
      African American and Caucasian women.
AB  - This study examined the association between a composite index of stress that
      included measures of life events, ongoing stress, discrimination, and economic
      hardship and subclinical carotid disease among 109 African America and 225
      Caucasian premenopausal women. African Americans reported more chronic stress and
      had higher carotid intima-media thickness (IMT) as compared with Caucasians.
      Among African Americans only, the composite stress index and unfair treatment
      were associated with higher IMT. These effects were partially mediated by
      biological risk factors. African American who reported experiencing racial
      discrimination had marginally more carotid plaque than did those who did not
      report experiencing racial discrimination. The results suggest that African
      Americans may be particularly vulnerable to the burden of chronic stress.

PMID- 12790259
TI  - Short-term effects of telephone therapy for breast cancer patients.
AB  - The authors report the short-term effects of a clinical trial testing 2 telephone
      therapies for breast cancer patients. Women (N = 222) with breast cancer were
      recruited and randomly assigned to cancer education, emotional expression, or
      standard care. Oncology nurses conducted 6 individual 30-min-therapy phone
      sessions. Women in the cancer education condition reported greater perceived
      control than women in the standard care condition. No treatment effects were
      obtained for mood or quality of life. These are the 1st data from a large-scale
      study testing telephone therapy, and they suggest that such therapies may be
      ineffective. Explanations for the results include therapy type and delivery,
      participant characteristics, short- versus long-term results, therapy conent, and
      whether therapy is necessary for breast cancer patients.

PMID- 12790261
TI  - Urinary incontinence in women. A surgeon's point of view.

PMID- 12790260
TI  - Psychological adjustment among African American breast cancer patients: one-year
      follow-up results of a randomized psychoeducational group intervention.
AB  - The effectiveness of support group interventions for cancer patients has been
      established among White patients but has been virtually unstudied among minority
      patients. The current study represents the 1st randomized support group
      intervention targeted to African American women with breast cancer. Participants
      (N = 73) with nonmetastatic breast cancer were randomly assigned to an 8-week
      group intervention or an assessment-only control condition At 12 months, the
      intervention resulted in improved mood as well as improved general and cancer
      specific psychological functioning among women with greater baseline distress or
      lower income. Subsequent research is needed to address effective methods of
      enrolling and following women with fewer psychosocial and financial resources, as
      they were the most likely to benefit from this particular intervention.

PMID- 12790262
TI  - Avoiding the family physician path.

PMID- 12790263
TI  - Correcting an apparent contradiction.

PMID- 12790264
TI  - Is a 5% decline in physician supply significant?

PMID- 12790265
TI  - "Welcome to our home, doctor".

PMID- 12790266
TI  - Effect of methotrexate on male fertility.
AB  - QUESTION: Several men with psoriatic arthritis have asked whether the
      methotrexate they take for rheumatoid arthritis will affect their fertility or
      the outcome of any of their partners' future pregnancies. What is known regarding
      risks to fertility and to fetuses? ANSWER: To date, there are no reports of
      adverse pregnancy outcomes among men exposed to methotrexate before conception.
      Opinions in the literature differ on the effects of methotrexate on male
      fertility. Several case reports and studies report no effect; others report
      reversible sterility. One limitation to several of these studies is the
      concurrent administration of other chemotherapeutic agents. Small studies
      reporting on methotrexate use with no other agents suggest no increased
      infertility. Motherisk is currently following men who are taking methotrexate
      alone for psoriatic arthritis to see whether it affects fertility.

PMID- 12790267
TI  - Ophthaproblem. Pseudotumour cerebri.

PMID- 12790268
TI  - Thoracic aortic dissection: distinguishing it from acute myocardial infarction.

PMID- 12790270
TI  - Are angry men more likely to develop cardiovascular disease?

PMID- 12790269
TI  - Immunizing adults against tetanus and diphtheria.

PMID- 12790271
TI  - Update on combined HRT.

PMID- 12790272
TI  - Urinary incontinence. Non-surgical management by family physicians.
AB  - OBJECTIVE: To review current evidence on conservative management of urinary
      incontinence (UI) by family physicians. QUALITY OF EVIDENCE: Articles were sought
      through MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CINAHL,
      PsycLit, ERIC, two consensus meetings, and review of abstracts presented at
      urology meetings. References of these articles were searched for relevant trials.
      Strong evidence supports bladder training, pelvic floor exercises, and some
      medications, but only fair evidence supports fluid adjustment, caffeine
      reduction, and stopping smoking. Weight loss and exercise are supported by expert
      opinion only. Consensus opinion is that, whenever possible, conservative
      management should be considered first. MAIN MESSAGE: Good evidence shows that
      initial management by primary care physicians is effective. After basic
      assessment and tests, strategies such as bladder retraining, pelvic floor
      exercises, and lifestyle modifications, augmented by appropriate medications, can
      be successful. If initial strategies are unsuccessful, patients can be referred.
      CONCLUSION: More than a million Canadians suffer from UI. In almost all cases,
      family physicians are the first health professionals contacted by patients. Basic
      assessment and conservative management can go far to ameliorate the problem.

PMID- 12790274
TI  - Short report: common parenting problems. Experience and comfort level in family
      medicine residency.

PMID- 12790275
TI  - Short report: care for people aged 75 and older. Independence, community care,
      and institutional care.

PMID- 12790273
TI  - Approach to urinary incontinence in women. Diagnosis and management by family
      physicians.
AB  - OBJECTIVE; To outline an approach to diagnosis and management of the types of
      urinary incontinence seen by family physicians. SOURCES OF INFORMATION:
      Recommendations for diagnosis are based on consensus guidelines. Treatment
      recommendations are based on level I and II evidence. Guidelines for referral are
      based on the authors' opinions and experience. MAIN MESSAGE: Diagnoses of stress,
      urge, or mixed urinary incontinence are easily established in family physicians'
      offices by history and gynecologic examination and sometimes a urinary stress
      test. There is little need for formal diagnostic testing. Management by family
      physicians (without need for specialist referral) includes lifestyle
      modification, pelvic floor muscle strengthening, bladder retraining, and
      pharmacotherapy with muscarinic receptor antagonists. Patients with pelvic organ
      prolapse might require specialist referral for consideration of pessaries or
      surgery, but family physicians can provide follow-up care. Women with more
      complex problems, such as severe prolapse or failed continence surgery, require
      referral. CONCLUSION: Urinary incontinence is a common condition in women. In
      most cases, it can be diagnosed and managed effectively by family physicians.

PMID- 12790276
TI  - Hand-held presentations.

PMID- 12790277
TI  - Teaching family medicine.

PMID- 12790278
TI  - Fostering interest in family medicine. Focusing on patient-physician
      relationships.

PMID- 12790279
TI  - Funding protected time for research. New opportunities from the Canadian
      Institutes of Health Research.

PMID- 12790280
TI  - Good health starts with us.

PMID- 12790281
TI  - Cooperative study of ruptured vertebrobasilar artery aneurysms in the Tohoku
      district in Japan.
AB  - A multicenter study investigated the clinical characteristics and overall outcome
      of 342 cases of ruptured vertebrobasilar artery aneurysms among 6783 ruptured
      intracranial berry aneurysms in 73 hospitals across the Tohoku district in Japan
      between 1992 and 1996. The incidence of ruptured vertebrobasilar artery aneurysms
      was less frequent than previously reported. The incidence was 5% among all
      intracranial berry aneurysms. One hundred eleven patients had aneurysms of the
      basilar artery bifurcation, 98 had vertebral-posterior inferior cerebellar artery
      aneurysms, 44 had basilar-superior cerebellar artery aneurysms, and 28 had distal
      posterior inferior cerebellar artery aneurysms. Aneurysm clipping was performed
      in 238 cases (70%), intravascular treatment in 22 (6%), drainage in 22 (6%), and
      conservative treatment in 60 (18%). Approximately 50% of patients were in good
      condition at admission. At 3-month follow up, 46% had good recovery, 14% had
      moderate disability, 10% had severe disability, 4% were vegetative state, and 27%
      died. Vertebral artery aneurysms showed favorable outcomes compared to basilar
      artery bifurcation aneurysms. Surgical results in the 238 operated cases were
      good recovery in 60%, moderate disability in 18%, severe disability in 10%,
      vegetative state in 2%, and death in 11% of cases. Worse postoperative outcomes
      were observed in patients with high preoperative Hunt and Kosnik grades or
      aneurysms larger than 10 mm, and in patients over 70 years of age.

PMID- 12790282
TI  - Long-term outcome for surgically treated cervical spondylotic radiculopathy and
      myelopathy.
AB  - Long-term follow-up results were examined to verify the efficacy of anterior
      osteophytectomy for cervical spondylotic myelopathy and radiculopathy, in
      particular the outcome for patients with developmentally narrow cervical canals
      and patients with associated ossification of the posterior longitudinal ligament
      (OPLL). One hundred thirty-nine patients who had undergone anterior
      osteophytectomy with interbody fusion between 1976 and 1990 were followed up for
      1 to 22.5 years (mean 11.4 years). Overall results evaluated by the neurosurgical
      cervical spine scale scoring and grading showed significant improvement in both
      improvement score (2.7 +/- 2.3) and improvement rate (52.3 +/- 45.7%). Lower
      extremity motor function improved in 66.1% of patients, upper extremity motor
      function in 82.0%, and sensory/pain function in 70.5%. Improvement ranged from
      one to three grades. Severely affected patients showed good recovery. Outcome for
      patients with narrow cervical canals (41 patients, 29.5%) did not differ
      significantly from that for patients with normal canals (98, 70.5%). Patients
      with associated OPLL (32 patients, 23.0%) had approximately the same outcomes as
      those with only spondylosis (107, 77.0%). Fifteen patients (10.8%) underwent
      reoperation because of myelopathy due to disc degeneration adjacent to the fused
      level (11 patients) or OPLL (4 patients). Anterior osteophytectomy with interbody
      fusion can achieve good outcomes in patients with cervical spondylotic myelopathy
      and radiculopathy, regardless of the size of the spinal canal and association
      with OPLL.

PMID- 12790283
TI  - Severe tension pneumocephalus caused by opening of the frontal sinus by head
      injury 7 years after initial craniotomy--case report.
AB  - A 46-year-old man presented with severe tension pneumocephalus triggered by mild
      head injury 7 years after craniotomy. He had a history of subarachnoid hemorrhage
      due to ruptured anterior communicating artery aneurysm, coating of the aneurysm
      performed via a craniotomy, and a ventriculoperitoneal (VP) shunt inserted. He
      fell from bed in a rehabilitation hospital. Eight hours after the injury, he
      became comatose and suffered general convulsion. He was then transferred to our
      hospital. Radiography and computed tomography (CT) revealed a large amount of
      intracranial air and a widely opened frontal sinus. On the day of admission, the
      shunt tube was ligated. Surgery was performed to repair the dura mater and close
      the frontal sinus. Postoperative CT revealed reduction in the amount of air and
      frontal sinus obstruction. The patient had a good postoperative course without
      meningitis. Tension pneumocephalus may occur as a complication several years
      after a craniotomy because of the chronic lowering of intracranial pressure
      induced by a VP shunt. Complete frontal sinus repair is important during the
      initial craniotomy.

PMID- 12790284
TI  - Aneurysm and fenestration of the azygos anterior cerebral artery--case report.
AB  - A 78-year-old female suffered sudden onset of nausea and headache. Computed
      tomography demonstrated diffuse subarachnoid hemorrhage. Cerebral angiography
      demonstrated an aneurysm arising from the right A1 segment of the azygos anterior
      cerebral artery, and the hypoplastic left A1. A right frontotemporal craniotomy
      was performed to obliterate the aneurysm by neck clipping. Surgical exploration
      found the fenestration of the right A1 and showed that the aneurysm had
      originated from the bifurcation of the fenestrated A1 and a small perforating
      artery arising from the fenestration. This unusual combination of an aneurysm
      associated with a fenestration of the right A1 and contralateral A1 hypoplasia
      may have been caused by local hemodynamic stress.

PMID- 12790285
TI  - Large vertebral arteriovenous fistula treated with stent-grafts--case report.
AB  - A 24-year-old woman presented with neck bruit and thrill. Neurological
      examination revealed no focal abnormality. Angiography and magnetic resonance
      imaging showed an arteriovenous fistula (AVF) at the C4-5 levels of the right
      vertebral artery (VA). The fistula had a single orifice that drained into the
      epidural veins via the C4-5 intervertebral foramen. A stent-graft was made of a
      3.9 cm balloon-expandable stent and an expandable polytetrafluoroethylene graft
      sutured outside the stent. The stent-graft was advanced through the femoral
      artery up to the VA but did not pass far enough distally to seal the entire
      fistula because of the high friction between the bulky device and the small
      vessel. Another 2 cm stent-graft was delivered and successfully positioned across
      the fistula. The AVF completely disappeared and the right VA was well preserved.
      Follow-up angiography at 3 weeks and 5 months after the treatment showed no
      fistula and no stenosis inside the stent-grafts. Stent-grafts are useful to treat
      AVF with a large orifice. The stent-graft is a promising technology to treat
      neurovascular diseases, although improvement is required for use in smaller
      vessels.

PMID- 12790286
TI  - Brainstem congestion caused by direct carotid-cavernous fistula--case report.
AB  - A 41-year-old woman presented with tinnitus in the left ear and headache,
      followed by diplopia and pain in the left cheek. Angiography showed a left high
      flow direct carotid-cavernous fistula (CCF), causing steal of the blood flow from
      the internal carotid artery into the cavernous sinus. A few days later, she
      rapidly developed right hemiparesis, dysarthria, and ocular conjugate deviation
      to the right, and became somnolent. Angiography at that time revealed occlusion
      of the superior petrosal sinus, causing engorgement of the veins in the
      surrounding brainstem. The CCF was completely embolized with interlocking
      detachable coils. Her consciousness disturbance and ophthalmoparesis dramatically
      improved within a few days, and the right hemiparesis and dysarthria gradually
      resolved. Magnetic resonance (MR) imaging after the treatment showed small
      pontine hemorrhage and perifocal edema but no ischemic lesions in the cerebral
      hemisphere. Re-evaluation of the MR imaging with gadolinium taken on admission
      demonstrated engorged veins in the brainstem parenchyma, which corresponded to
      the hemorrhagic lesion in the brainstem. Brainstem congestion caused by direct
      CCF is very rare, but it can be life-threatening. Good outcome can be expected if
      the CCF is completely occluded before congestive hemorrhage occurs.

PMID- 12790287
TI  - Panhypopituitarism induced by cholesterol granuloma in the sellar region--case
      report.
AB  - A 67-year-old man with generalized fatigue and weight loss developed
      hyponatremia. Endocrinologic examination demonstrated panhypopituitarism.
      Magnetic resonance imaging showed a pituitary mass extending slightly to the
      suprasellar region. Transsphenoidal resection of the tumor was performed.
      Histological examination found exclusively granulomatous tissue with cholesterol
      clefts, and no epithelial component. This cholesterol granuloma may be classified
      as xanthogranuloma of the sellar region.

PMID- 12790288
TI  - Orbital malignant fibrous histiocytoma with extension to the base of the skull-
      case report.
AB  - An 18-year-old woman presented with a malignant fibrous histiocytoma (MFH)
      originating in the orbit and invading the frontal and temporal base of the skull
      manifesting as exophthalmos and double vision that had persisted for 2 months.
      Magnetic resonance imaging revealed a tumor in the left orbit that extended as
      far as the frontal and temporal base of the skull. The tumor was treated by
      radical resection with conservation of the eyeball and its contents, followed by
      orbit wall reconstruction. The histological diagnosis was MFH. Local radiotherapy
      was administered postoperatively. The preoperative symptoms improved, and there
      has been no evidence of local recurrence or metastasis in the year since the
      surgery. In this case, radical resection of the tumor was essential. Furthermore,
      the adjuvant therapy was apparently successful, probably because this
      histological type of tumor is highly sensitive to radiotherapy.

PMID- 12790289
TI  - Fracture and lateral dislocation of the T12-L1 vertebrae without neurological
      deficit--case report.
AB  - A 21-year-old man suffered T12-L1 vertebrae fracture and lateral dislocation
      without neurological deficit. Computed tomography and magnetic resonance imaging
      demonstrated the fracture and lateral dislocation of the thoracolumbar spine. The
      injured spine was realigned with rods and screws, and bony fusion of the affected
      vertebrae was performed. Patients with thoracolumbar fracture-dislocation without
      neurological deficit may suffer unintended neurological injury secondary to
      maneuvers that cause further dislocation of the spine. Severe spinal injury
      without neurological deficit should be evaluated in detail, especially with
      spinal computed tomography. Internal fixation and reduction are recommended if
      the patient's condition is suitable for surgery.

PMID- 12790290
TI  - Head and neck extension-fixation with a head frame for exposure of the distal
      internal carotid artery in carotid endarterectomy--technical note.
AB  - Adequate exposure of the distal internal carotid artery (ICA) for carotid
      endarterectomy may be difficult to achieve because of the position of the
      mandible and associated soft tissues. A simple yet effective use of a head frame
      is described to gain several centimeters of exposure of the distal ICA. The
      patient's head and neck are fixed in an extension position using a radiolucent
      head frame. Nasotracheal intubation and secure taping of the chin are also
      employed to keep the mouth closed and to prevent the mandible from spontaneously
      hanging down. The head frame tightly fixes the patient's neck, so the mandible
      does not disturb the surgical field throughout the operation. This simple method
      maximizes exposure of the distal ICA. The radiolucent head frame also enables
      intraoperative angiography to confirm the patency of the ICA and the absence of
      flap formation. This simple technique is useful for exposing the distal ICA.

PMID- 12790291
TI  - Adhesion of 4-META/MMA-TBB resin to heated dentin: effects of pre-treatments with
      FeCl3 and/or HEMA.
AB  - The purpose of this study was to compare the tensile bond strengths (TBSs) and
      failure mode of 4-META/MMA-TBB resin to 60 degrees C-heated and unheated bovine
      dentin, especially to investigate the influence of ferric chloride contained in
      citric acid pre-conditioning. In addition, the effect of HEMA priming for heated
      dentin was also evaluated. The TBSs to heated dentin were significantly lower
      than those to unheated dentin. Adhesive failures were observed in most specimens
      of the heated and HEMA-non primed group. HEMA application to heated dentin
      significantly increased the TBSs in each acid conditioning, which were also
      significantly higher than those of the unheated and ferric chloride-contained
      citric acid-conditioned group. It was clarified that heating dentin decreased the
      bond strength without HEMA priming even if the dentin surfaces were acid
      conditioned with 10-3, while HEMA priming after acid conditioning recovered the
      bond strength.

PMID- 12790292
TI  - Precipitation hardening in a dental low-gold alloy.
AB  - Age-hardening characteristics in a dental low-gold alloy composed of 40.0 wt% Au
      35.0 wt% Ag-7.9 wt% Pd-7.0 wt% Cu-5.0 wt% In-3.5 wt% Zn-1.5 wt% Sn, were
      investigated by means of the hardness test, XRD study, SEM observations and EPMA.
      The following results were obtained. The age-hardening was characterized by a
      precipitation of Cu-rich alpha2 phase in the a phase. The softening that occurred
      following prolonged ageing was due to the heterogeneous formation of the fine
      nodular precipitates composed of the Ag-rich alpha1 phase and the Cu-rich alpha2
      phase at the grain boundaries of the a phase.

PMID- 12790293
TI  - Effects of zinc treatment in patients with recurrent aphthous stomatitis.
AB  - The purpose of this study was to assess the effects of systemic zinc sulfate in
      the treatment of recurrent aphthous stomatitis (RAS) by atomic absorption
      spectrophotometry. The study was carried out on 40 patients with RAS. The first
      group consisted of 20 subjects with RAS who were administered zinc sulfate (220
      mg) once per day for one month. In the second group, there were 20 subjects with
      RAS who were administered placebo (saccharose). Results showed that the levels of
      serum zinc before treatment were under the normal value in the 42.5% percent of
      the patients with RAS. Saliva ALP, serum zinc, serum albumin, and serum alkaline
      phosphates activity for group II were significantly lower than those for group I
      after treatment (p < 0.01). After 1 month of zinc therapy the aphthae reduced and
      did not reappear for 3 months. The empirical use of systemic zinc sulfate
      supplementation in the treatment of RAS is recommend.

PMID- 12790294
TI  - Impact strength of acrylic denture base resin reinforced with woven glass fiber.
AB  - This study investigated the effect of the number and position of woven glass
      fibers in denture base resin matrix on its impact strength. Test specimens were
      reinforced with woven glass fiber 0.5, 1.0, or 1.5 mm below the surface. The
      impact strength was tested using an Izod-type impact tester with an impact speed
      of 335 cm/s, which simulates dropping the denture, and using a flywheel-type
      impact tester with a two-point support at 13.5 and 75.0 cm/s, which simulates the
      chewing. The woven glass fibers had a strengthening effect in all tests, and the
      impact resistance was further improved when the woven glass fibers were
      positioned more superficially in the resin. The results suggest that woven glass
      fiber is an effective reinforcement in denture base resin.

PMID- 12790295
TI  - Effect of depth and tubule direction on ultimate tensile strength of human
      coronal dentin.
AB  - The purpose of this study was to evaluate the effect of dentin depth and tubule
      direction on the ultimate tensile strength (UTS) of human dentin. Dentin slabs of
      0.5-mm thickness were trimmed either from the mesial and distal (for specimens
      with the tubules parallel to the tensile force; parallel group) or from the
      occlusal and pulpal surfaces (perpendicular group) to reduce the cross-sectional
      area of the superficial, middle, and deep regions to 0.25 mm2, and subjected to
      microtensile testing. From SEM photomicrographs of the fractured specimens of the
      parallel group, the tubule density was investigated. For both parallel and
      perpendicular groups, superficial dentin showed a significantly higher UTS than
      deep dentin. The tubule density of superficial dentin was significantly lower
      than that of middle and deep dentin. When performing the microtensile bond test
      to deep dentin, it is possible that cohesive failure of dentin can occur at
      relatively low tensile stresses.

PMID- 12790296
TI  - Studies on MMA-TBB resin II. The effect of dual use of TBB and other initiators
      on polymerization of PMMA/MMA resin.
AB  - The effects of dual use of tributylborane (TBB) and benzoyl peroxide/ N,N
      dimethyl-p-toluidine (BPO/DMPT) or camphorquinone/N,N-dimethyaminoethyl
      methacrylate (CQ/DMAEMA), as well as BPO/DMPT and CQ/DMAEMA for comparison
      purposes, on postpolymerization of PMMA/MMA resin were examined from the view
      point of long term changes of residual MMA and molecular weight. Each resin was
      polymerized and analyzed by high performance liquid chromatography and size
      exclusion chromatography. The effect of dual use of TBB and BPO/DMPT or CQ/DMAEMA
      on polymerization of PMMA/MMA resin was additive in nature and each initiator
      system worked rather independently without little interaction between the two.
      TBB was effective especially during the period of postpolymerization. On the
      other hand, BPO/DMPT used in combination with CQ/DMAEMA had a limited effect only
      during the initial period and little effect during postpolymerization. It was
      suggested that TBB was most suitable as a chemically accelerated initiator
      component for a dual cure system.

PMID- 12790297
TI  - Caries diagnosis using a laser fluorescence system--observation of
      autofluorescence of dental caries--.
AB  - The purpose of this study was to evaluate the usefulness of autofluorescence of
      carious lesions on caries diagnosis. The observation of the micromorophology of
      caries lesions was conducted using a confocal laser scanning microscope, a
      fluorescence microscope and a WDX type electron probe X-ray microanalyzer.
      Observation of autofluorescence under Cy5 and UV fields showed clearly specific
      images of autofluorescence in the carious lesion. However, observation of
      autofluorescence under FITC field showed images of autofluorescence with unclear
      boundaries in the carious lesion. EPMA images showed decreases in Ca and P in the
      carious areas. As a result of the observation of autofluorescence and the EPMA
      images in the carious lesion, a correlation was noted between autofluorescence
      under the Cy5 field as the laser fluorescence apparatus for caries diagnosis and
      demineralized areas. The usefulness of autofluorescence of carious lesion on
      caries diagnosis was suggested.

PMID- 12790299
TI  - Electron probe micro-analysis of a contact probe after Er:YAG laser tooth
      ablation.
AB  - The purpose of this study was to investigate the contact probes of Er:YAG laser
      before and after tooth ablation. Three kinds of contact probe were prepared. The
      first was an unused probe (NE). The second was used to prepare 10 cervical
      cavities (KP). The third was a probe that was judged for an exchange by three
      dentists who had expertise with Er:YAG laser (EX). The surface observation and
      mapping analysis were performed. The contact surface of NE was a flat and smooth
      surface, only Si was observed. KP demonstrated an uneven surface, Si was observed
      throughout, with scattered indications of Ca and P. EX displayed regions of
      fracture along the edge and a surface exhibiting dissolved adherents in parts. It
      was suggested that micro-explosions have effects on not only the tooth substance,
      but also the contact surface of the probe.

PMID- 12790298
TI  - Evaluation of adhesive defects using an ultrasonic pulse-reflection technique.
AB  - The purpose of this study was to examine the application of an ultrasonic pulse
      reflection technique for the evaluation of adhesive defects. First, the sonic
      velocities in the enamel and dentin of human molars and bovine incisors were
      measured with a pulsar receiver attached to an ultrasonic transducer. The
      identification of the dentino-enamel junction and pulp-dentin interface using the
      ultrasonic method based on intrinsic sonic velocities showed good agreement with
      the actual measured thicknesses. Next, a cemented restoration with artificial
      faults was prepared. Half of the Au-Ag-Pd alloy plate area was cemented to the
      dentin slab using luting resin cement. The adhesive interface was evaluated with
      a high-resolution ultrasonic imaging system. Clear internal faults were evident
      from the ultrasonic tomogram. The findings of this study suggest that the
      ultrasonic pulse-reflection technique may be useful for inspecting and imaging
      structural defects of adhesive interfaces.

PMID- 12790301
TI  - Ions released from dental amalgams in contact with titanium.
AB  - The ions released from conventional and high-copper amalgams in contact with
      titanium were quantitatively analyzed in a 0.9% NaCl solution at 37 degrees C
      when the surface area ratio of titanium/amalgam was set up as 1/10, 1/1, or 10/1.
      The corrosion potentials of the amalgams and titanium were measured under the
      same conditions. Surface analyses on the amalgams were also employed using SEM
      with WDS. Though the potential of the conventional amalgam was always lower than
      that of titanium, that of the high-copper amalgam was reversed during the early
      stage of immersion and remained lower. When the surface area ratio of titanium
      grew at 10/1, tin and copper ions released from the conventional and high-copper
      amalgam, respectively, increased significantly compared with those of each
      amalgam that was not in contact with titanium. The galvanic corrosion in such a
      large surface area of titanium possibly led to the heavy corrosion of the
      amalgams.

PMID- 12790300
TI  - Development of casting investment preventing blackening of noble metal alloys
      part 1. Application of developed investment for Ag-Pd-Cu-Au alloy.
AB  - The objective of this study is to develop a casting investment that prevents the
      blackening of the cast surface of noble metal alloys. The experimental
      investments were prepared using a gypsum-bonded investment in which the metallic
      powders such as boron (B), silicon (Si), aluminum (Al) and titanium (Ti) were
      added as oxidizing agents. An Ag-Pd-Cu-Au alloy was cast into the mold made of
      the prepared investment. The effect of the addition of each metal powder was
      evaluated from the color difference between the as-cast surface and the polished
      surface of the cast specimen. The color of the as-cast surface approached that of
      the polished surface with increasing B and Al content. A lower mean value in the
      color difference was obtained at 0.25-1.00 mass% B content. B and Al are useful
      as an additive in a gypsum-bonded investment to prevent the blackening of an Ag
      Pd-Cu-Au alloy. The effects of Si and Ti powder addition could not be found.

PMID- 12790302
TI  - Moving child-psychiatric nursing into the 21st century--revisited.

PMID- 12790303
TI  - Psychotherapeutic treatment outcomes in grandparent-raised children.
AB  - PROBLEM: Few studies have focused on grandparent-raised children with behavioral/
      emotional problems. The present study examined the therapeutic progress of this
      population. METHODS: Data from this descriptive, correlational study were
      obtained from records of 207 children who received treatment at a child treatment
      center. Instruments included the Progress Evaluation Scales (PES) and an
      investigator-constructed tool. FINDINGS: Children who had regular paternal
      contact, were younger when treatment started, and were raised by grandparents
      with adult partners had significantly more positive change in the PES scores.
      CONCLUSIONS: More thorough clinical assessment of these reconfigured families
      will lead to improved mental health outcomes for children and will enhance
      clinical records as sources of research data.

PMID- 12790304
TI  - Depression in adolescents with diabetes.
AB  - TOPIC: Prevalence and interventions for depression in youth with type 1 diabetes.
      PURPOSE: To explore the co-morbidity of youth with diabetes and psychiatric
      conditions, and evaluate the relationship of youth with co-morbid depression and
      diabetes on glycemic control, quality of life, family support, behavioral
      problems, attributional style, and self-esteem. SOURCES: Relevant literature in
      both child and adolescent populations of psychiatry, psychology, and nursing.
      CONCLUSIONS: Youth with type 1 diabetes have significantly higher rates of
      depression over the general population. Seratonin reuptake inhibitors, cognitive
      behavioral treatment, interpersonal therapy, improving family communication and
      problem-solving skills, and diabetes education hold promise as treatment that can
      decrease depression in youth with diabetes. Advanced practice nurses are
      positioned to provide these interventions and treatments.

PMID- 12790305
TI  - A model of recovery from substance abuse and dependence for Korean adolescents.
AB  - PROBLEM: There is a need for a model that illuminates the recovery process from
      substance abuse and dependence for Korean adolescents, identifies the stages and
      strategies of recovery, and directs interventions to specific stages. METHODS:
      The model was developed from content analysis focused on the experiences during
      the recovery process of 8 Korean adolescents with substance abuse and dependence.
      CONCLUSIONS: The stages in recovery include retracing, accepting, surrendering,
      and turning to change. The strategies of recovery involve a variety of activities
      and multidimensional domains. The model integrates the stages and strategies of
      recovery, and suggests nursing interventions to promote recovery of adolescents
      with a substance-related disorder.

PMID- 12790306
TI  - Richness of collaboration for children's response to disaster.

PMID- 12790307
TI  - False-negative primary neonatal thyroid screening: the need for clinical
      vigilance and secondary screening.
AB  - The screening of newborn babies for congenital hypothyroidism has changed the
      natural history of this abnormality. We describe here a case of a female patient
      with congenital hypothyroidism that was missed by primary neonatal thyroid
      screening (using thyroid-stimulating hormone) at two days of age; it was detected
      only after the development and persistence of jaundice during the first three
      weeks of life. A normal neonatal screening result does not preclude the
      development of hypothyroidism later in infancy. Clinical vigilance must be
      maintained by practitioners. A second screening between two and six weeks of age
      may be useful in order to detect the few cases missed at first screening.

PMID- 12790308
TI  - Assays for thyroid-stimulating hormone using dried blood spotted filter paper
      specimens to screen for hypothyroidism in older children and adults.
AB  - OBJECTIVE: Symptoms of hypothyroidism in adults can be mistaken for medical and
      psychiatric diseases, as well as for general signs of ageing such as weakness,
      lethargy and fatigue. The incidence of hypothyroidism is many-fold higher in
      adults than in newborn children. The latter have been routinely screened for the
      condition using filter paper dried blood spots (DBS) for nearly three decades but
      this cost-effective screening technique has only recently been applied to adults.
      This study was undertaken to show that DBS testing in adults and older children
      is an accurate way to screen for hypothyroidism. METHODS: Serum and DBS specimens
      were collected from adults and children. Assays were run on both specimens and
      the results correlated. In addition 972 specimens were collected from adults at
      community centres and nursing homes. Follow-up studies were performed on patients
      with positive results. RESULTS: The correlation coefficient for 118 matched serum
      and DBS specimens was 0.99. Thyroid-stimulating hormone (TSH) values were
      elevated in 50 of the 972 adults from nursing homes and community centres.
      Thirteen of these individuals were on thyroid medication and 28 had either high
      serum TSH or high thyroglobulin (TgAb) or thyroid peroxidase (TPOAb) antibody
      levels. CONCLUSIONS: Individuals can be screened for hypothyroidism by collecting
      finger stick DBS specimens at community centres, nursing homes and other
      locations which can be mailed by regular postal service to a central laboratory
      for accurate and inexpensive testing.

PMID- 12790309
TI  - Hereditary haemochromatosis and hepatocellular carcinoma in males: a strategy for
      estimating the potential for primary prevention.
AB  - OBJECTIVES: Homozygosity for the C282Y mutation of the HFE gene is the main cause
      of iron overload in hereditary haemochromatosis. This study calculated the number
      of hepatocellular carcinoma cases among a cohort of white males that could be
      attributed to C282Y homozygosity. A better understanding of the extent of
      potentially preventable mortality arising from this cancer might help with
      decision making about the feasibility of population screening. METHODS: We
      combined information from published life tables, age-specific cancer rates and
      DNA studies of archived liver biopsy specimens to calculate the number of cases
      of hepatocellular carcinoma that might occur during the lifetime of a cohort of
      1,000,000 men, including a subgroup of 5000 C282Y homozygotes. RESULTS:
      Hepatocellular carcinoma was estimated to occur in 2673 men in the cohort
      (1:374); 267 of these cases were in the subgroup of 5000 C282Y homozygotes
      (1:17). If these 267 cases were prevented, the remaining lifetime risk among all
      males would be 1:416. The relative risk for this cancer in C282Y homozygotes is
      23. CONCLUSIONS: There continues to be uncertainty about the efficacy of
      screening for haemochromatosis. Hepatocellular carcinoma is the most readily
      quantifiable serious health problem attributable to this source. Further
      confirmatory DNA (C282Y) studies would be helpful in larger, unbiased sets of
      archived biopsy specimens, as a way to confirm the present estimate. Any strategy
      designed to prevent attributable liver cancer is likely to prevent other serious
      problems from haemochromatasis as well.

PMID- 12790310
TI  - Performance of the recommendations of a British advisory group for screening for
      chlamydia in a sample of women in general practice.
AB  - In this study the performance of the guidelines produced by the British Chief
      Medical Officer's expert advisory group for selective screening for Chlamydia
      trachomatis was evaluated. The guidelines were applied to a sample of 777 women
      in general practice in Antwerp, Belgium. The accuracy of the screening/testing
      recommendations was suboptimal. The model detected 90% of infections but failed
      to identify a high-risk population; the population to be screened was reduced by
      only 21%. The focus on young age as the most important determinant for screening
      was not appropriate. More attention should be paid to risky sexual behaviour.

PMID- 12790311
TI  - Contribution of clinical breast examination to mammography screening in the early
      detection of breast cancer.
AB  - OBJECTIVES: As the benefit of clinical breast examination (CBE) over that of
      screening mammography alone in reducing breast cancer mortality is uncertain, it
      is informative to monitor its contribution to interim measures of effectiveness
      of a screening programme. Here, the contribution of CBE to screening mammography
      in the early detection of breast cancer was evaluated. SETTING: Four Canadian
      organised breast cancer screening programmes. METHODS: Women aged 50-69 receiving
      dual screening (CBE and mammography) (n = 300,303) between 1996 and 1998 were
      followed up between screen and diagnosis. Outcomes assessed by mode of detection
      (CBE alone, mammography alone, or both CBE and mammography) included referral
      rate, positive predictive value, pathological features of tumours (size, nodal
      status, morphology), and cancer detection rates overall and for small cancers (<
      or = 10 mm or node-negative). Heterogeneity in findings across programmes was
      also assessed. RESULTS: On first versus subsequent screen, CBE alone resulted in
      28.5-36.7% of referrals, and 4.6-5.9% of cancers compared with 52.6-60.1% of
      referrals and 60.0-64.3% of cancers for mammography alone. Among cancers detected
      by CBE, 83.6-88.6% were also detected by mammography, whereas for
      mammographically detected cancers only 31.7-37.2% were also detected by CBE. On
      average, CBE increased the rate of detection of small invasive cancers by 2-6%
      over rates if mammography was the sole detection method. Without CBE, programmes
      would be missing three cancers for every 10,000 screens and 3-10 small invasive
      cancers in every 100,000 screens. CONCLUSIONS: Inclusion of CBE in an organised
      programme contributes minimally to early detection.

PMID- 12790312
TI  - Informed consent for breast screening: what should we tell women?
AB  - OBJECTIVE: To illustrate visually the lifetime probabilities of the principal
      outcomes of the UK breast screening programme in a readily understandable format.
      METHODS: We derived prognostic data from a modelling exercise using published
      effectiveness data and routine data sources. We calculated the probability that a
      woman will survive to the age of 75 if she chooses to participate fully in breast
      screening from age 50 to 64 and if she chooses not to participate. We also
      calculated her probability of being referred for assessment, undergoing fine
      needle biopsy and undergoing open biopsy. We present these data in two
      alternative decision aid formats. These alternative formats illustrate visually
      the outcomes for 1000 women and 100 women choosing each alternative: breast
      screening or no breast screening. RESULTS: A woman participating in breast
      screening from age 50 to 64 increases her chances of surviving to age 75 by 0.6%.
      She has a 21.8% probability of surviving to age 75 and being referred for
      assessment but no further investigation. She has a 5.7% probability of undergoing
      core biopsy and a 0.9% probability of undergoing open biopsy. This information
      can easily be presented visually. CONCLUSIONS: We can provide realistic estimates
      of the effects of the breast screening programme on mortality in a readily
      understandable format. If we wish women to make an informed choice about breast
      screening they must be given this information.

PMID- 12790313
TI  - Does evidence-based information about screening for prostate cancer enhance
      consumer decision-making? A randomised controlled trial.
AB  - OBJECTIVES: Efforts to educate men about the controversy surrounding prostate
      cancer screening are well intended but rarely evaluated rigorously. We evaluated
      an evidence-based (EB) booklet for men designed to promote informed decision
      making. We also determined whether men's preference for involvement in decision
      making ("passive", "collaborative" or "active") modified its impact. SETTING AND
      METHODS: Men aged 40-70 years were recruited from the practices of 13 local
      general practitioners (GPs) in Sydney, Australia. They completed a self
      administered questionnaire before seeing their GP, who, according to pre
      randomised codes, distributed either our EB booklet or conventional information.
      Post-test questionnaires were mailed to men three days later. Of the 248 eligible
      men recruited, 214 (86% response rate) returned post-test questionnaires.
      Knowledge of evidence and of risk of developing and dying from prostate cancer,
      attitudes, interest in screening for prostate-specific antigen (PSA), worry and
      decisional conflict were the main outcome measures. RESULTS: Compared with those
      receiving conventional information, men receiving the EB booklet had
      significantly improved knowledge (50% of items correct, 95% CI 46-53%; vs 45%
      correct, 95% CI 42-48%) (p = 0.048) and lower levels of decisional conflict (mean
      21.6, 95% CI 20.7-22.5; vs mean 24.3, 95% CI 23.4-25.2) (p < 0.001). Interest in
      PSA screening was significantly reduced in both groups at post-test (p < 0.001).
      Men preferring a "passive" approach to decision-making gained as much from our EB
      booklet as those with "active" or "collaborative" preferences. CONCLUSIONS: Our
      findings show the benefits of providing evidence-based information to men about
      PSA screening. Our EB booklet facilitated informed choice, even among "passive"
      decision-makers.

PMID- 12790314
TI  - Screening for vulnerability to psychological disorders in the military: an
      historical survey.
AB  - OBJECTIVES: To evaluate attempts in the military to screen for vulnerability to
      psychological disorders from World War I to the present. METHODS: An extensive
      literature review was conducted by hand-searching leading medical and
      psychological journals relating to World Wars I and II. Recent publications were
      surveyed electronically and UK archives investigated for British applications.
      RESULTS: Despite the optimism shown in World War I and the concerted efforts of
      World War II, follow-up studies showed that screening programmes did not succeed
      in reducing the incidence of psychological casualties. Furthermore, they had a
      counter-productive effect on manpower, often rejecting men who would have made
      good soldiers. Continued experimentation with screening methods for psychiatric
      vulnerability failed to yield convincing results during the post-war period.
      CONCLUSIONS: Although well-measured variables, such as intelligence, have been
      shown to predict success in training and aptitude, no instrument has yet been
      identified which can accurately assess psychological vulnerability. Previous
      attempts have failed because of false-positives, false-negatives and reluctance
      in the target population because of stigma. Early findings suggest that
      psychological surveillance, if not screening, may yield valuable results when
      applied to military populations exposed to stress.

PMID- 12790315
TI  - A likelihood ratio approach to meta-analysis of diagnostic studies.
AB  - OBJECTIVE: To develop a clinically and methodologically sound approach to
      diagnostic meta-analysis. METHODS: Two-step model was used involving four
      fictitious sets of 10 studies each with varying sensitivity and specificity; this
      was followed by the application of the method to data from a published systematic
      review of emergency ultrasound. Multidimensional test characteristics (relating
      to the detection or exclusion of the condition of interest) were described by
      likelihood ratio scatterplots and pooled likelihood ratios. Likelihood ratios
      summarise the ability of a test to revise the prior probability of disease. They
      can be summarised by established fixed-effects and random-effects methods.
      RESULTS: Likelihood ratios precisely describe both directions of test
      performance. By plotting positive against negative likelihood ratios, together
      with their 95% confidence intervals, a multidimensional forest plot is obtained
      that can be interpreted in analogy to therapeutic meta-analyses. There are
      accepted threshold values of positive and negative likelihood ratios (i.e. 10.0
      and 0.1) to recommend a test for clinical use. In the matrix space, distinct test
      characteristics can even be assessed by eyeballing. With regard to data from the
      real meta-analysis, the suggested high discriminatory power of ultrasound was
      only partially qualified by likelihood ratios. The positive value confirms the
      reliability of a positive scan, whereas the negative value questions a normal
      sonogram. CONCLUSIONS: A full characterisation of test performance requires
      multidimensional effect measures. Likelihood ratios are recommended descriptors
      of the two dimensions of diagnostic research evidence and provide a convenient
      means to visualise and to communicate results as weighted summary estimates of a
      diagnostic meta-analysis.

PMID- 12790317
TI  - The urokinase receptor (uPAR, CD87) as a target for tumor therapy: uPA-silica
      particles (SP-uPA) as a new tool for assessing synthetic peptides to interfere
      with uPA/uPA-receptor interaction.
AB  - Many different processes in the physiology and pathophysiology of human beings
      are regulated protein/protein interactions such as receptor/ligand interactions.
      A more detailed knowledge of the nature of receptor/ligand binding sites and
      mechanisms of interaction is necessary as well in order to understand the process
      of cancer spread and metastasis. For instance, the cell surface receptor uPAR
      (CD87) and its ligand, the serine protease urokinase-type plasminogen activator
      (uPA), facilitate tumor invasion and metastasis in solid malignant tumors.
      Besides its proteolytic function in activating the zymogen plasminogen into the
      serine protease plasmin, binding of uPA to tumor cell-associated uPAR initiates
      various cell responses such as tumor cell migration, adhesion, proliferation, and
      differentiation. Hence, the tumor-associated uPA/uPAR system is considered a
      potential target for cancer therapy. Here we briefly describe a new technology
      using micro-silica particles coated with uPA (yields SP-uPA) and reaction of SP
      uPA with recombinant soluble uPAR (suPAR) to test the competitive antagonistic
      potential of synthetic uPA peptides by flow cytofluorometry (FACS). We discuss
      the data obtained with the SP-uPA system from two different points of view: (1)
      The enhanced potential of improved uPA-derived synthetic peptides compared to
      previously described peptides, and (2) comparison of the new technique to other
      test systems currently used to identify uPA/uPAR or other protein/protein
      interactions.

PMID- 12790316
TI  - Comparing the observed and predicted effectiveness of folic acid fortification in
      preventing neural tube defects.

PMID- 12790319
TI  - Stromal cell involvement in cancer.
AB  - Solid tumors co-opt the body's endogenous extracellular proteolytic machinery for
      their invasion and metastasis. This is supported by a large number of independent
      observations ranging from histochemical and prognostic studies of cancer patient
      material to animal experiments. There are several extracellular proteolytic
      systems that are relevant in the context of cancer, but the plasminogen
      activation (PA) system and the matrix metalloproteases (MMPs) remain the most
      thoroughly investigated. Localization studies by immunohistochemistry and in situ
      mRNA hybridization in tumors of common human cancers have repeatedly identified
      members of the PA and MMP systems in stromal cells. The cancer cells, of
      epithelial origin, contribute PA and MMP components in some cases, but their
      contribution fades in comparison with the overwhelming expression of proteolytic
      components by fibroblasts, macrophages, endothelial cells, and other stromal
      cells. Ideal animal models of human cancers should recapitulate this fundamental
      proteolytic aspect of tumor biology. However, in the transplantable tumor models
      where PA or MMP components have been studied at the cellular level in vivo, this
      is most often not the case. Transgenic cancer models may provide a closer
      parallel to the human situation, in that PA and MMP components are synthesized by
      the tumor stroma. The pivotal role of stromal cells has been confirmed
      experimentally in mouse models in which the expression pattern of proteolytic
      components is strongly reminiscent of human tumors. In these models it is
      possible to reconstitute the wild-type tumor characteristics of proteolytically
      deficient tumor-bearing mice by transplantation with wild-type fibroblasts or
      hemapoietic cells. These studies collectively show that cancer-associated
      proteolysis is a collaborative effort of malignant cancer cells and various
      stromal cells--a collaboration in which stromal cells contribute the majority of
      the active proteolytic components that are necessary for the invasive behavior of
      the tumors. This cellular division of labor positions the stromal cells as prime
      targets for future research and possibly therapy. Vascular endothelial cells are
      already the focus of intense therapeutically relevant research, but tumor
      associated fibroblasts, macrophages, neutrophils, lymphendothelial cells, etc.
      provide additional largely unexplored territory in the ongoing search for
      efficient countermeasures against invasive cancer.

PMID- 12790318
TI  - Molecular regulation of urokinase-receptor gene expression as one potential
      concept for molecular staging and therapy.
AB  - The urokinase-receptor (u-PAR) is a central molecule of invasion and metastasis
      promoting plasminogen-dependent extracellular matrix degradation in diverse
      carcinoma types such as gastric or colon cancer. Overexpression of u-PAR has been
      reported to occur mainly at the transcriptional level in malignant cells, and has
      been shown to indicate a poor clinical prognosis of cancer patients. This review
      will give an overview on experimental findings on u-PAR and its function,
      molecular mechanisms of its regulation, and its impact for future clinical
      decision planning and potential therapeutic concepts.

PMID- 12790320
TI  - Inhibition of the tumor-associated urokinase-type plasminogen activation system:
      effects of high-level synthesis of soluble urokinase receptor in ovarian and
      breast cancer cells in vitro and in vivo.
AB  - Tumor cell invasion and metastasis depend on the coordinated and temporal
      expression of proteolytic enzymes to degrade the surrounding extracellular matrix
      and of adhesion molecules to remodel cell-cell and/or cell-matrix attachments.
      The tumor cell-associated urokinase-type plasminogen activator system, consisting
      of the serine protease uPA, its substrate plasminogen, its membrane-bound
      receptor uPAR, as well as its inhibitors PAI-1 and PAI-2, plays an important role
      in these pericellular processes. Especially, association of the proteolytic
      activity of uPA with the cell surface via interaction with uPAR significantly
      increases the invasive capacity of tumor cells. Consequently, various approaches
      have been pursued to interfere with the expression or activity of uPA and/or
      uPAR, including antisense strategies and the development of active-site
      inhibitors of uPA or inhibitors of uPA/uPAR interaction. In this review, we focus
      on the results obtained in vitro and in vivo with tumor cells producing high
      levels of a recombinant soluble form of uPAR, which efficiently inhibits uPA
      binding to cell surface-associated uPAR and, by this, acts as a scavenger for
      uPA.

PMID- 12790321
TI  - Molecular mechanisms of carcinogenesis in gastric cancer.
AB  - The catalog of gene alterations in human cancer grows rapidly. Gastric cancer is
      no exception and displays gene changes in multiple oncogenes, suppressor genes,
      and DNA repair genes. Clinically relevant molecules whose expression or structure
      is altered include the plasminogen activator (uPA) and its inhibitor PAI-1
      (plasminogen activator inhibitor type 1), the cell-cycle regulator cyclin E,
      epidermal growth factor (EGF), the apoptosis inhibitor bcl-2, the cell adhesion
      molecule E-cadherin, and the multifunctional protein beta-catenin. In addition,
      genetic instability is commonly seen. Gene amplification and protein
      overexpression of the growth factor receptors c-erbB2 and K-sam may be prognostic
      factors for intestinal-type and diffuse-type gastric cancer, respectively. The
      clinical implications of some of the recent findings for diagnosis and therapy
      are discussed.

PMID- 12790322
TI  - Clinical implications of molecular diagnosis in hereditary nonpolyposis
      colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary cancer
      predisposition accounting for approximately 1%-5% of all colorectal cancers.
      Clinical management of HNPCC families is most challenging due to the following
      factors: (1) reduced penetrance of approximately 80%; (2) predisposition to
      cancer of the colorectum but also of the endometrium, urinary tract and small
      bowel; (3) broad inter- and intrafamilial heterogeneity; and (4) highly
      accelerated adenoma carcinoma sequence in the colorectum. To date, HNPCC may be
      defined either by the so-called Amsterdam I+II criteria or by detection of a
      mutation in one of the mismatch repair genes. Once the positive mutation has been
      identified, predictive testing of at-risk family members is available. Screening
      recommendations for clinically identified families, mutation carriers, and their
      unaffected at-risk relatives must be defined for clinical management. The
      question of prophylactic colectomy in HNPCC is also discussed.

PMID- 12790323
TI  - Minimal residual disease in gastric cancer.
AB  - In curatively resected gastric cancer, the incidence of distant relapse is as
      high as 30%. Although the most important factor contributing to the local control
      of the tumor is the microscopic tumor-free margin of the surgical resection, the
      occurrence of distant metastases is in many cases due to preoperative or
      perioperative tumor cell dissemination. In addition to the established TNM
      staging system, disseminated tumor cells may serve as independent prognostic
      factors influencing patient outcome after curative surgery. Basically, in gastric
      cancer three compartments have been identified in which single tumor cells may be
      shed: lymph nodes, peritoneal cavity, and bone marrow. Assessment of resected
      regional lymph nodes with monoclonal antibodies directed against cytokeratin
      antigens leads to an upstaging in comparison with conventional histology. Nodal
      micrometastases detected by immunohistochemistry result in an upstaging of up to
      36% of patients. However, their prognostic significance remains controversial.
      Local dissemination of tumor cells in the peritoneal cavity determines the
      outcome in advanced gastric cancer and diffuse-type carcinoma. Patients with
      negative peritoneal washings seem to have a more favorable prognosis. Moreover,
      with the use of these diagnostic tools, patient subpopulations may be identified
      which profit from intraperitoneal therapy regimens. Diffuse hematogenous tumor
      cell dissemination into the bone marrow has been shown to be a prognostic factor
      in several studies. In our own population of 180 gastric cancer patients, bone
      marrow cells were screened immunohistochemically with a monoclonal antibody
      directed against cytokeratin 18 (CK18). In 95 patients (53%), CK2-posititve cells
      were detected. In a multivariate analysis, the independence of the presence of
      three or more disseminated tumor cells per 10(6) mononuclear cells was proven to
      be a prognostic factor in patients with intestinal-type tumors, pT1/2 status, and
      pN0 status. In conclusion, the TNM status only partially reflects the actual
      extent of systemic disease in patients with resected gastric cancer. The
      assessment of minimal residual disease is valuable in estimating the prognosis in
      many patients. In the future, staging systems will have to not only include TNM
      data but also provide specific information on biological properties of residual
      cancer cells in order to establish more exact prognostic estimates and provide
      patients with an individually tailored multimodal treatment.

PMID- 12790324
TI  - Minimal residual disease in breast cancer and gynecological malignancies:
      phenotype and clinical relevance.
AB  - In breast cancer, about 35% of patients without any clinical signs of overt
      distant metastases already have disseminated tumor cells in bone marrow aspirates
      at the time of primary therapy. A significant prognostic impact of these
      disseminated tumor cells has been shown by many international studies: patients
      with tumor cells in their bone marrow have a significantly worse prognosis than
      those without them. Even in malignancies where the skeletal system is not a
      preferred location for distant metastasis, such as ovarian cancer, early presence
      of minimal residual disease (MRD) is correlated with poor patient outcome. Thus,
      besides analysis of the primary tumor, detection of MRD can be used for
      assessment of patient prognosis and for prediction or monitoring of response to
      systemic therapy. Disseminated tumor cells are also the targets for novel tumor
      biological therapy approaches such as specific antibody-based therapies against
      target cell-surface antigens such as HER2, Ep-CAM (17-1A), and uPA-R. In breast
      cancer, a first antibody-based tumor therapy against HER2 (Herceptin) has already
      been approved for clinical use in recurrent disease. However, patient selection
      for such tumor biological therapies becomes rather difficult due to phenotype
      changes, which may manifest themselves as differences between primary lesion and
      disseminated tumor cells. Therefore, not only identification of disseminated
      tumor cells but even more so their characterization at the protein and gene
      levels have become increasingly important. In conclusion, characterization of
      tumor biological properties of disseminated tumor cells allows identification of
      patients with breast cancer or gynecological malignancies at risk for relapse who
      are likely to benefit from systemic treatment and/or novel tumor biological
      therapy approaches.

PMID- 12790325
TI  - Advanced statistical methods for the definition of new staging models.
AB  - Adequate staging procedures are the prerequisite for individualized therapy
      concepts in cancer, particularly in the adjuvant setting. Molecular staging
      markers tend to characterize specific, fundamental disease processes to a greater
      extent than conventional staging markers. At the biological level, the course of
      the disease will almost certainly involve interactions between multiple
      underlying processes. Since new therapeutic strategies tend to target specific
      processes as well, their impact will also involve interactions. Hence, assessment
      of the prognostic impact of new markers and their utilization for prediction of
      response to therapy will require increasingly sophisticated statistical tools
      that are capable of detecting and modeling complicated interactions. Because they
      are designed to model arbitrary interactions, neural networks offer a promising
      approach to improved staging. However, the typical clinical data environment
      poses severe challenges to high-performance survival modeling using neural nets,
      particularly the key problem of maintaining good generalization. Nonetheless, it
      turns out that by using newly developed methods to minimize unnecessary
      complexity in the neural network representation of disease course, it is possible
      to obtain models with high predictive performance. This performance has been
      validated on both simulated and real patient data sets. There are important
      applications for design of studies involving targeted therapy concepts and for
      identification of the improvement in decision support resulting from new staging
      markers. In this article, advantages of advanced statistical methods such as
      neural networks for definition of new staging models will be illustrated using
      breast cancer as an example.

PMID- 12790326
TI  - Clinical implications of the EGF receptor/ligand system for tumor progression and
      survival in gastrointestinal carcinomas: evidence for new therapeutic options.
AB  - The epidermal growth factor (EGF) receptor and its various ligands (EGF, TGF
      alpha, amphiregulin, heparin-binding (HB)-EGF, heregulin, betacellulin) seem to
      be involved in the growth regulation of intestinal mucosa and might be related to
      the development and progression of gastrointestinal tumors. However, few
      quantitative data investigating the impact of tumor-EGF receptor levels in
      gastrointestinal carcinomas on tumor stage and prognosis are available.
      Therefore, EGF receptors were quantitatively determined in colorectal carcinomas
      in comparison to adjacent normal mucosa by 125I[EGF]-binding studies. EGFR
      capacity was increased in advanced invasive colorectal carcinomas (T1/2 vs. T3/4
      tumors, p<0.001) and advanced UICC stages (UICC I vs. UICC II/III, p<0.001).
      These findings were confirmed with quantitative 125[I]EGF autoradiography
      performed on frozen tissue slides and analyzed by laser densitometry (p=0.020).
      EGF receptor analysis with immunohistochemistry with EGFR antibodies directed
      against the extracellular domain of the receptor was not correlated with tumor
      invasion or prognosis. mRNA-expression of EGFR ligands was investigated using
      semiquantitative RT-PCR amplification using specific primers. RT-PCR transcripts
      of EGFR ligands (EGF, TGF-alpha, HB-EGF, and amphiregulin) were detected in both
      carcinomas and normal mucosa, indicating that autocrine growth stimulation of
      colorectal carcinomas is mediated by coexpression of EGF receptor ligands and
      upregulation of EGF receptors. Survival of colorectal cancer patients with
      increased tumor EGF receptor levels was significantly reduced in comparison to
      patients with low/unchanged tumor EGF receptor levels (mean survival+/-SD, 36.2+/
      4.0 vs. 46.8+/-4.3 months; p=0.017). Further studies investigating EGF receptor
      levels in gastric cancer patients have shown that increased tumor EGF receptor
      levels were associated with poor prognosis in gastric cancer patients with tumors
      localized distal from the cardia. Several specific EGF receptor tyrosine kinase
      inhibitors have recently entered clinical phase I-III studies, with promising
      antitumor effects in several tumors, including gastrointestinal cancer.
      Therefore, patients with invasive gastric or colorectal carcinomas might benefit
      from therapies specifically blocking EGFR-mediated signal transduction.

PMID- 12790327
TI  - Minimal residual disease in bone marrow and peripheral blood of patients with
      metastatic breast cancer.
AB  - The presence of occult micrometastases in bone marrow (BM) of patients with early
      breast cancer increases the risk of relapse. Detection of circulation tumor cells
      in peripheral blood (PB) may also influence the patient's prognosis. Few data are
      available on the correlation between tumor cell dissemination in BM and PB in
      solid epithelial tumors. Twenty-milliliter blood samples were collected from PB
      of 42 patients with advanced breast cancer and centrifuged using the density
      gradient OncoQuick (OncoQuick Greiner BioOne, Frickenhausen, Germany). The BM
      aspirates available from 11 of the 42 patients were centrifuged using density
      centrifugation Ficoll. Tumor cell detection was performed by microscopy after
      cytospin preparation and immunocytochemical staining with the monoclonal antibody
      A45-B/B3. Cytokeratin-positive cells were detected in 23 patients (55%) in the PB
      and in three patients (27%) in the BM. A cohort with bone lesions as the only
      metastatic side showed a correlation as follows: 7 of the 11 patients (64%) had
      negative findings in BM and PB, whereas cytokeratin-positive cells in PB were
      present in 3 of these 11 patients (27%). The presence of visceral metastases was
      associated with the detection of cytokeratin-positive cells in the PB in 20 of
      the 31 patients (65%) in this subgroup. The density gradient OncoQuick in
      combination with immunocytochemical staining allows the detection of cytokeratin
      positive cells in PB of patients with advanced breast cancer. The
      immunocytochemical detection of cytokeratin-positive cells in PB seems to be
      associated with the site of metastatic manifestation.

PMID- 12790329
TI  - Detection of circulating tumor cells in blood using an optimized density gradient
      centrifugation.
AB  - The aim of the study was to compare the new density gradient centrifugation
      system OncoQuick with the standard density gradient centrifugation system Ficoll
      for improved tumor cell enrichment in blood of tumor patients. Evaluation of
      OncoQuick and Ficoll density gradient centrifugation was performed by flow
      cytometry and immunocytochemistry using 10 ml unspiked and tumor cell-spiked
      blood samples of tumor-free probands. From 10 ml blood, OncoQuick density
      gradient centrifugation separated a cell fraction which consisted of a mean cell
      number of 9.5x10(4) mononuclear cells compared to 1.8x10(7) cells by Ficoll.
      Density gradient centrifugation of tumor cell-spiked blood samples with OncoQuick
      and Ficoll led to similar tumor cell recovery rates, between 70% and 90% for both
      methods. The improved depletion of mononuclear blood cells by OncoQuick
      simplified further immunocytochemical evaluation of the enriched cell fraction,
      which could be spun onto 1-2 glass slides by cytocentrifugation. In comparison,
      the mononuclear cells separated by Ficoll had to be spun onto more than 50 glass
      slides for complete immunocytochemical evaluation. Consequently, tumor cell
      density on each cytospin was higher after OncoQuick preparation compared to
      Ficoll. Density gradient centrifugation with OncoQuick results in higher relative
      tumor cell enrichment than Ficoll density gradient centrifugation. This
      simplifies further immunocytochemical tumor cell detection and is a promising
      tool for the detection of circulating tumor cells in blood of tumor patients.

PMID- 12790328
TI  - Estrogen receptor expression profile of disseminated epithelial tumor cells in
      bone marrow of breast cancer patients.
AB  - The estrogen receptor (ER) status in primary breast cancer represents an
      important prognostic factor and has a profound impact on therapeutic decisions.
      However, ER expression profile on disseminated breast cancer cells is largely
      unknown, although these cells are one of the main target structures in adjuvant
      therapy after local curative resection (R0) achieved in most breast cancer
      patients. Thus, the present pilot study was designed to evaluate the ER
      expression profile on disseminated epithelial cells in bone marrow, one of the
      preferential organs for manifestation of distant metastases in breast cancer.
      Using the alkaline phosphatase anti-alkaline phosphatase-immunogold double
      staining procedure, in a panel of 17 breast cancer patients, epithelial cells
      (mab CK2) detected in bone marrow were analyzed for ER expression (mab 1D5) and
      compared with ER expression in the corresponding primary tumors. Whereas eleven
      of the 17 patients (64.7%) were ER-positive in primary carcinomas, only two
      patients (11.8%) revealed ER-positive epithelial cells in bone marrow. In
      addition, one of these two patients demonstrated a heterogeneous ER expression
      pattern, with both ER-positive and ER-negative epithelial cells in bone marrow.
      Although in both of these cases the ER-positive epithelial cells in bone marrow
      derived from ER-positive primary tumors, in this small patient cohort none of the
      prognostic relevant clinical and pathological factors tested, i.e., TNM
      classification, grading, and ER status in primary breast cancer, correlated with
      the ER status in bone marrow. The striking discrepancy between ER expression in
      primary breast cancers and the corresponding disseminated epithelial cells in
      bone marrow suggests either the selective dissemination of ER-negative tumor
      cells into the bone marrow or a negative impact of the bone marrow
      microenvironment on epithelial ER expression. This phenomenon might influence
      therapeutic effects of antihormonal treatment.

PMID- 12790330
TI  - Antitumoral and antimetastatic effects of continuous particle-mediated cytokine
      gene therapy.
AB  - We established a mice tumor model to investigate the effects of continuous cancer
      gene therapy, including antigen-presenting cell (APC) engineering and local
      stimulation of the immune system. B16 melanoma or Lewis lung carcinoma cells were
      injected intradermally on the back of C57/BL6 mice. The overlaying dermis or the
      tumor was shot with a gene gun (particle-mediated gene transfer) starting 8 days
      after tumor implantation in the case of the melanoma (Lewis lung carcinoma start
      day 7), continuing every fourth day thereafter until death. Control groups were
      mice without any therapy (A) or gene therapy with the empty plasmid (B). Therapy
      groups (Melanoma) received the genes as follows: group C--day 8, IL-12; day 12,
      IL-2...; group D--day 8, IFN-gamma/B7.1; day 12, IFN-gamma/B7.1...; group E--day
      8, IFN-gamma/B7.1; day 12, IL-12, day 16, IL-2.... Melanoma: Mean survival time
      was enhanced in all therapy groups significantly, whereby the greatest survival
      time was found in group C. Tumor growth was reduced in all therapy groups
      similarly (C and D significant). Lewis Lung: Only mice of group C had an enhanced
      survival and reduced tumor growth (both significant). An antimetastatic effect
      was seen in all therapy groups.

PMID- 12790331
TI  - Genetic subtyping of renal cell carcinoma by comparative genomic hybridization.
AB  - The prognosis of renal cell carcinoma (RCC) varies dependent on histologic tumor
      subtypes. However, differentiation between RCC types may sometimes be difficult
      on histologic grounds alone. Furthermore, the prognostic value of histologic
      parameters for the individual prognosis is limited. Additional information on the
      molecular level seems necessary to obtain more certainty in diagnostic and
      prognostic evaluation. By investigating genetic alterations in different RCC
      subtypes, we sought to obtain a genotype-phenotype correlation. Eighty-two clear
      cell, 53 papillary, 23 chromophobe RCCs and 26 renal oncocytomas were
      investigated. Comparative genomic hybridization (CGH) was performed on DNA from
      paraffin-embedded tissue samples. DNA was isolated from tumor areas by
      microdissection and amplified by degenerated oligonucleotide primed polymerase
      chain reaction (DOP-PCR). CGH was performed according to standard protocols. We
      were able to detect specific alterations in each RCC subtype: clear cell RCC
      showed -3p, +5/5q, -8p, -9, -14, -18; papillary (chromophilic) RCC gains of
      chromosomes 7, 17, 16, 3, 12; chromophobe RCC loss of chromosomes 1, 2, 6, 10,
      13, 17, 21; renal oncocytomas loss of chromosomes 1/1p and 14. Furthermore, for
      clear cell RCC, it was possible to define alterations which are associated with
      metastatic disease: loss of 9, 10, 14. Our results demonstrate that each RCC
      subtype is characterized by distinct genetic alterations. The definition of
      genetic alterations seems helpful for a tumor typing especially when morphology
      is equivocal. Therefore, genetic analyses represent a powerful diagnostic and
      prognostic tool for RCC.

PMID- 12790332
TI  - Telomere length and hTERT expression in patients with colorectal carcinoma.
AB  - The stabilization of telomere length by telomerase activation is an important
      step in carcinogenesis. Quantification of the catalytic telomerase subunit hTERT
      (human Telomerase Reverse Transcriptase) is a new indirect measure for
      telomerase. Telomere length and hTERT expression in cancer tissue and
      corresponding normal mucosa of 57 patients with completely resected colorectal
      carcinoma (UICC stage I-IV, R0) were determined for correlation with
      histopathological parameters and survival. Telomere lengths were measured using
      Southern Blot and hTERT-encoding mRNA was quantified by real-time RT-PCR.
      Telomere length and hTERT expression were significantly correlated in normal
      mucosa and cancer tissue (p<0.001). Telomere length and hTERT expression
      decreased with ageing only in normal mucosa. Cancer tissue had significantly
      shorter telomeres (p<0.001) and significantly lower hTERT expression levels
      (p<0.001) than corresponding normal mucosa. UICC stage I tumors showed
      significantly shorter telomeres than UICC stage II-IV tumors (p<0.002). Telomere
      length and hTERT expression were significantly correlated with overall survival.
      Telomere length and hTERT expression play an important role in ageing and
      carcinogenesis. Both parameters were identified as prognostic factors in patients
      with colorectal carcinoma.

PMID- 12790333
TI  - Estimation of concentration of chosen adhesive factors in suprarenal tumours of
      'incidentaloma' type.
AB  - The role of adhesive molecules in the pathogenesis of adrenal gland tumours
      formation remains unclear. Here we present the concentrations of soluble vascular
      cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1
      (sICAM-1) in the blood of patients with adrenal "incidentaloma". We found that
      the mean concentrations of sVCAM and sICAM in the serum of the patients with
      adrenocortical cancers were significantly higher than those of the patients with
      benign adenomas or control cases. These results suggest that the levels of
      adhesion molecules may be a marker of malignancy of adrenal incidentalomas.

PMID- 12790334
TI  - Evaluation of the levels of bFGF, VEGF, sICAM-1, and sVCAM-1 in serum of patients
      with thyroid cancer.
AB  - Tumour growth and development depend on a complex cascade of angiogenic factors.
      The aim of the study is evaluation of the level of growth factors VEGF and bFGF,
      and adhesion molecules sICAM-1, sVCAM-1 in the serum of patients with papillary
      thyroid cancer. The study comprised 35 patients aged 21-68 years (mean age 46+/
      14) who had papillary thyroid cancer diagnosed on the basis of thin needle
      aspiration biopsy, and were qualified for operative treatment. This group
      comprised 28 women and seven men. The control group was 26 healthy individuals.
      Serum concentrations of bFGF, VEGF, sICAM-1, and sVCAM-1 were evaluated by the
      enzyme-linked immunosorbent assay (ELISA) method. We have observed significantly
      higher mean concentrations of bFGF, VEGF, and sICAM-1 in the serum of patients
      with thyroid cancer compared with the control group. There was no significant
      difference between the sVCAM-1 concentrations of the thyroid cancer group and the
      control group.

PMID- 12790335
TI  - Molecular whole-body cancer staging using positron emission tomography:
      consequences for therapeutic management and metabolic radiation treatment
      planning.
AB  - A prospective analysis was performed in 124 non-small cell lung cancer patients
      to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission
      tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring
      after induction-chemotherapy (n=34), and conformal radiation treatment planning
      (n=27). Staging by FDG-PET was significantly more accurate than CT (p<0.001) and
      changed therapeutic management in 52% of all patients. After induction
      chemotherapy, patients with complete metabolic remission histologically did not
      show vital tumor cells in contrast to patients with metabolic partial remission
      or progressive disease. Metabolic radiation treatment planning by PET led to
      smaller planning target volumes (PTVs) for radiation therapy (between 3% and 21%
      in 25/27 patients), resulting in a reduction of dose exposure to healthy tissue.
      In two patients, PET-PTV was larger than CT-based PTV, since PET detected lymph
      node metastases smaller than 1 cm. FDG-PET provides clinically important
      information; changes therapeutic management, can predict noninvasively
      effectiveness of chemotherapy, and may lead to better tumor control with less
      radiation-induced toxicity.

PMID- 12790336
TI  - Recurrences of thyroid cancer after radical surgery and complementary treatment:
      are macroscopic, microscopic, scintigraphic, and biochemical criteria sufficient
      in the evaluation of radicality of primary treatment?
AB  - From 1974 to 1999, 1,001 patients were operated on for thyroid cancer, including
      778 (78%) for differentiated thyroid cancer and 223 (22%) for other thyroid
      malignant neoplasms. Radical operations were performed in 716 (92%) patients with
      differentiated thyroid cancer and in 85 (38%) patients with other thyroid
      malignant neoplasms. After surgery, all patients underwent various methods of
      complementary treatment, depending on cancer type and grading (levothyroxine,
      131I, radiotherapy and/or chemotherapy). These patients had no evidence of
      persistent disease after finishing treatment (Tg, CEA, calcitonin, scintigraphy).
      We observed recurrences of thyroid cancer, although macroscopic, microscopic,
      biochemical, and scintigraphic criteria of radicality were present. At 18 months'
      to 24 years' follow-up, we observed recurrences in 94 (11.7%) of 801 patients
      treated radically, including in 53 (7.4%) of 716 patients with differentiated
      thyroid cancer and in 41 (48%) of 85 patients with other thyroid malignancies.
      Among 37 patients with thyroid bed recurrence, 18 (48.6%) underwent radical
      operations and 19 (51.4%) palliative ones. Of 33 patients with regional lymph
      node recurrence, radical operations were performed in 26 (78.8%) and palliative
      ones in seven (21.2%). Of 24 patients with distant metastases, four (17%) (with
      single metastasis) underwent surgery (three radical operations and one palliative
      one). Other methods of treatment were used in the remaining patients. Occurrence
      of thyroid cancer recurrences in the thyroid bed and lymph nodes indicates that
      macroscopic, microscopic, and scintigraphic criteria of radicality are not
      sufficient. Recurrences after radical surgery are more infrequent in patients
      with differentiated thyroid cancers than in those with other thyroid malignant
      neoplasms. In many patients, thyroid bed and lymph node recurrences can be
      removed radically during surgery.

PMID- 12790337
TI  - Summary and congress report: molecular staging of cancer--concepts of today,
      therapies of tomorrow.

PMID- 12790338
TI  - Chemical and pharmacological investigations of Epimedium species: a survey.
AB  - More than 130 different compounds have been identified from over 16 species of
      the Epimedium genus of the Berberidaceae family. Eight of these species have been
      used in the Traditional Chinese Medicines (TCM) over centuries to treate a wide
      range of diseases. From in vitro and in vivo experimental data, and preliminary
      structure-activity relationship (SAR) analysis of the androgenic/anti-estrogenic
      and anti-oxidant activities of the icariin series of flavonoids and glycosides,
      the results appear to be consistent with those of known anti-estrogenic
      flavonoids, such as luteolin. Further QSAR analysis of the different active
      ingredients is now in progress and will be reported elsewhere. Our survey
      suggests the possibility of multiple targets and multiple mechanisms of action by
      Epimedium preparations and their purified compounds. These may serve as leads for
      further new drug development.

PMID- 12790339
TI  - Potential of p38 MAP kinase inhibitors in the treatment of cancer.
AB  - The involvement of chronic inflammation in tumor development and progression is
      reviewed. Based on the natural history of certain diseases and epidemiology
      studies, a strong association has been established between particular chronic
      inflammatory conditions and eventual tumor appearance. Solid tumors require a
      stroma for their growth and recruit macrophages to synthesize essential growth
      and angiogenic factors that they do not have the capacity to produce. The
      microenvironment of the local host tissue appears to be an active participant in
      exchanging cytokines and enzymes with tumor cells that modify the local
      extracellular matrix, stimulate migration, and promote tumor angiogenesis,
      proliferation and survival. The role of p38 MAP kinase as a therapeutic target
      for treating cancer is discussed.

PMID- 12790340
TI  - Therapeutic role of peroxisome proliferator-activated receptors in obesity,
      diabetes and inflammation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor family and play a significant role in regulation of lipid metabolism,
      hepatic peroxisomal enzyme expression, insulin sensitivity and glucose
      homeostasis. PPARs have been classified into three subtypes encoded by different
      genes: PPARalpha (NR1C1), PPARdelta (NR1C2), and PPARgamma (NR1C3). Each subtype
      of PPARs appears to be differently expressed in a tissue-specific manner because
      of their binding to specific consensus DNA sequences, known as PPREs (peroxisome
      proliferator response elements). Thus, PPARs have emerged as potential molecular
      targets for the design and synthesis of a different class of compounds,
      considering the conformation of receptors for the treatment of human metabolic
      disorders. This review covers the rapid progress made in functional analysis of
      PPARs and progress made towards the identification of ligands for each subtype
      receptor.

PMID- 12790341
TI  - Quasispecies and the development of new antiviral strategies.
AB  - RNA virus populations consist of complex and dynamic mutant distributions, rather
      than defined genomic sequences. This feature confers great adaptability on
      viruses and is partly responsible for current difficulties of viral disease
      prevention and control. Mutant distributions, also termed mutant swarms or mutant
      clouds, were first proposed in a theory of molecular evolution termed
      quasispecies theory. The theoretical formulation of quasispecies and its links to
      present day RNA viruses are discussed. The need to accommodate antiviral
      strategies to the dynamic nature of viral populations is emphasized. In
      particular, recent results on viral extinction associated with enhanced
      mutagenesis (virus entry into error catastrophe) are reviewed and presented as an
      example of how the understanding of viruses as quasispecies could lead to a
      potential practical application in medicine.

PMID- 12790342
TI  - Maximizing the value of genomics in the drug discovery and development process.
AB  - Genomics and all the associated technologies it has spawned have fundamentally
      changed the way research and development organizations carry out the work they do
      in the early stages of discovery. However, successful organizations must move
      from product concept through to registration as efficiently as possible. In order
      to achieve this, the early "basic" science must be combined with the clinical
      perspective from the start. Furthermore, since the genomics industry was first
      established in the early 1990s it has evolved from tool and data suppliers to
      drug development companies. It is therefore likely that we will see technology
      advances in genomics become more limited in the years ahead.

PMID- 12790343
TI  - Quantitative structure-activity relationships of carbonic anhydrase inhibitors.
AB  - A review is presented of quantitative structure-activity relationships (QSARs) of
      different categories of carbonic anhydrase (CA) inhibitors, which are basically
      benzenesulfonamides, heterocyclic sulfonamides and aliphatic sulfonamides. The
      review shows that in all categories, the inhibition potency depends largely on
      the electronic properties of the sulfonamide group, which can be affected by the
      electronic characteristics of the substituents present on the nucleus (benzene or
      heterocyclic ring) of the sulfonamide molecules. Substituents themselves can be
      involved, along with the nucleus, in some dispersion interaction with the enzyme.
      Based on this review, a schematic model is presented to represent the interaction
      of sulfonamides with the CA.

PMID- 12790344
TI  - Crystallins, genes and cataract.
AB  - Far from being a physical entity, assembled of inanimate structural proteins, the
      ocular lens epitomizes the biological ingenuity that sustains an essential and
      near-perfect physical system of immaculate optics. Crystallins (alpha, beta, and
      gamma) provide transparency by dint of their high concentration, but it is
      debatable whether proteins that provide transparency are any different,
      biologically or structurally, from those that are present in non-transparent
      structures or tissues. It is becoming increasingly clear that crystallins may
      have a plethora of metabolic and regulatory functions, both within the lens as
      well as outside of it. Alpha-crystallins are members of a small heat shock family
      of proteins and beta/gamma-crystallins belong to the family of epidermis-specific
      differentiation proteins. Crystallin gene expression has been studied from the
      perspective of the lens specificity of their promoters. Mutations in alpha-, beta
      , and gamma-crystallins are linked with the phenotype of the loss of
      transparency. Understanding catalytic, non-structural properties of crystallins
      may be critical for understanding the malfunction in molecular cascades that lead
      to cataractogenesis and its eventual therapeutic amelioration.

PMID- 12790345
TI  - Current and potential therapies for the treatment of herpes-virus infections.
AB  - Human herpesviruses are found worldwide and are among the most frequent causes of
      viral infections in immunocompetent as well as in immunocompromised patients.
      During the past decade and a half a better understanding of the replication and
      disease-causing state of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2),
      varicella zoster virus (VZV), and human cytomegalovirus (HCMV) has been achieved
      due in part to the development of potent antiviral compounds that target these
      viruses. While some of these antiviral therapies are considered safe and
      efficacious (acyclovir, penciclovir), some have toxicities associated with them
      (ganciclovir and foscarnet). In addition, the increased and prolonged use of
      these compounds in the clinical setting, especially for the treatment of
      immunocompromised patients, has led to the emergence of viral resistance against
      most of these drugs. While resistance is not a serious issue for immunocompetent
      individuals, it is a real concern for immunocompromised patients, especially
      those with AIDS and the ones that have undergone organ transplantation. All the
      currently approved treatments target the viral DNA polymerase. It is clear that
      new drugs that are more efficacious than the present ones, are not toxic, and
      target a different viral function would be of great use especially for
      immunocompromised patients. Here, an overview is provided of the diseases caused
      by the herpesviruses as well as the replication strategy of the better studied
      members of this family for which treatments are available. We also discuss the
      various drugs that have been approved for the treatment of some herpesviruses in
      terms of structure, mechanism of action, and development of resistance. Finally,
      we present a discussion of viral targets other than the DNA polymerase, for which
      new antiviral compounds are being considered.

PMID- 12790346
TI  - Human auditory steady-state responses.
AB  - Steady-state evoked potentials can be recorded from the human scalp in response
      to auditory stimuli presented at rates between 1 and 200 Hz or by periodic
      modulations of the amplitude and/or frequency of a continuous tone. Responses can
      be objectively detected using frequency-based analyses. In waking subjects, the
      responses are particularly prominent at rates near 40 Hz. Responses evoked by
      more rapidly presented stimuli are less affected by changes in arousal and can be
      evoked by multiple simultaneous stimuli without significant loss of amplitude.
      Response amplitude increases as the depth of modulation or the intensity
      increases. The phase delay of the response increases as the intensity or the
      carrier frequency decreases. Auditory steady-state responses are generated
      throughout the auditory nervous system, with cortical regions contributing more
      than brainstem generators to responses at lower modulation frequencies. These
      responses are useful for objectively evaluating auditory thresholds, assessing
      suprathreshold hearing, and monitoring the state of arousal during anesthesia.

PMID- 12790347
TI  - Reliability and validity of the (modified) Amsterdam Inventory for Auditory
      Disability and Handicap.
AB  - This study investigated the psychometric adequacy of the (modified) Amsterdam
      Inventory for Auditory Disability and Handicap ((m)AIAD). The original version of
      the AIAD was developed by Kramer et al in 1995. Special emphasis was placed on
      the statistical aspects of the scores, because these properties place limits on
      the clinical utility of the instrument. The AIAD is a self-assessment
      questionnaire that consists of 30 questions covering all the relevant factors of
      disability in individual hearing functioning in daily life. This paper reports
      data from 94 subjects, aged 17-65 years, with different hearing abilities, who
      completed a modified version of the AIAD and the Hearing Disability Questionnaire
      (HDQ), on two occasions 1 month apart. The psychometric adequacy of the AIAD was
      determined by measuring its reliability and validity. Factor analysis was
      performed, and the reliability was tested by measuring internal consistency,
      split-half correlation, and test-retest reproducibility. The validity was tested
      by measuring construct and criterion validity. The results showed that the
      reliability of the (m)AIAD was highly satisfactory, with good internal
      consistency, high split-half correlations, and high test-retest correlations.
      Construct validity showed a high correlation between scores on the (m)AIAD and
      scores on the HDQ. Criterion validity showed a moderate but significant
      correlation between scores on the (m)AIAD and hearing thresholds in dB HL.

PMID- 12790348
TI  - Effect over time of allopurinol on noise-induced hearing loss in guinea pigs.
AB  - Temporary threshold shift (TTS) and permanent threshold shift (PTS) may follow
      prolonged noise exposure. Several reports suggest that noise-induced damage to
      the cochlea may be related to the activity of reactive oxygen species (ROS).
      Drugs that scavenge or block ROS formation also protect the cochlea. Guinea pigs,
      treated with allopurinol, were exposed to white noise (120 dB SPL) or impulse
      noise (114 dB SPL) for 2 and 5 h. The protective effect of allopurinol was
      confirmed, but, at these levels of sound, it was present only after noise
      exposure up to 2 h. This study also offers evidence suggesting that allopurinol
      does not influence the establishment of PTS.

PMID- 12790349
TI  - Comment on 'horizontal localization and speech intelligibility with bilateral and
      unilateral hearing aid amplification', by S. Kobler and U. Rosenhall.

PMID- 12790350
TI  - Facio-lingual width of the alveolar base.
AB  - Importance is attached to assessment of anterior facio-lingual maxillary and
      mandibular apical base widths in determining limits to incisor root movements.
      There is absence of similar assessment of facio-lingual base widths for premolars
      and molars. The aims of this paper are two-fold: to determine the strength of
      associations between the facio-lingual widths of the anterior and buccal alveolar
      apical bases, and to determine if an association might exist between the
      posterior alveolar base width and specific lateral cephalometric measurements.
      Comparative measurements were made on 40 adult Thai skulls and their companion
      mandibles using lateral cephalometric radiographs, linear tomography, and direct
      measurements of the dento-alveolar and basal structures. Wide variation was found
      in facio-lingual widths of the alveolar bases. No significant correlations were
      found between the facio-lingual widths of the anterior and posterior alveolar
      bases in the maxillae and mandible. Significant inverse correlations were found
      between the alveolar base widths at the mandibular incisors and the FP-MP and PP
      MP angles, and between maxillary incisor base widths and the gonial angle.
      Importantly, no cephalometric indicators were found to predict posterior alveolar
      base widths. There is a need to continue to search for assessment indicators.

PMID- 12790351
TI  - In vitro surface corrosion of stainless steel and NiTi orthodontic appliances.
AB  - Simulated fixed orthodontic appliances were constructed, immersed and incubated
      in artificial saliva for periods up to three months. Two types of stainless steel
      archwires and two types of NiTi wires were used. The surface corrosion of the
      archwires was determined macroscopically, with scanning electron microscopy, and
      with spectrophotometry. The deposits on the wires were identified with X-ray
      diffraction. Uniform corrosion was observed on stainless steel wires, and a
      slight colour change was detected on the NiTi wires beneath stainless steel
      ligatures. The corrosion product on the stainless steel wires increased with
      immersion time, and the surface oxide films were easily detached from the
      underlying matrix. Crevice corrosion was observed under deposits of oxide, and at
      the interface between bracket and band. Such corrosion may weaken a wire or weld
      leading to fracture. In contrast, the NiTi archwires did not corrode, and there
      was no significant difference in surface morphology. The stainless steel
      archwires showed a significant loss of reflectance after heat treatment and
      immersion in artificial saliva. The NiTi archwires had the same reflectance
      before and after the immersion test. NiTi archwires are significantly more stable
      and resistant to corrosion than stainless steel archwires.

PMID- 12790352
TI  - Some factors associated with open gingival embrasures following orthodontic
      treatment.
AB  - Open gingival embrasures or "black triangles" can be an undesirable outcome of
      adult orthodontic treatment. The aims of the present study were to determine the
      prevalence of open gingival embrasures in a group of orthodontic patients, and to
      determine if open gingival embrasures were related to: age at the start of
      treatment, the severity of pretreatment crowding of the mandibular incisors, the
      duration of treatment or changes in alveolar bone height. The subjects were 80
      orthodontic patients (33 males, 47 females) between 15 and 31 years of age. Open
      gingival embrasures were found in 43.7 per cent of all subjects, while in
      subjects over 20 years of age the prevalence was 66.7 per cent. In relation to
      the amount of crowding 42.8 per cent of the subjects with less than 4 mm crowding
      had open gingival embrasures, 41.2 per cent of those with between 4 and 8 mm
      crowding had open gingival embrasures, and 50 per cent of those with more than 8
      mm crowding had open gingival embrasures. The groups were not significantly
      different. Approximately 42 per cent of the subjects in the shorter treatment
      group had open gingival embrasures, and 44.4 per cent of those whose treatment
      took longer than 3 years had open gingival embrasures. This difference was not
      statistically significant. Cephalometric measurements of mandibular alveolar bone
      height indicate that open gingival embrasures were more likely to be due to
      resorption of the alveolar crest rather than extrusion of the mandibular
      incisors. In conclusion, open gingival embrasures were more frequently found in
      patients over 20 years of age than in younger patients, and were associated with
      resorption of the alveolar crest.

PMID- 12790353
TI  - Cervical vertebral maturation as a predictor of the adolescent growth spurt.
AB  - The aim of this study was to investigate the application of an improved version
      of the Cervical Vertebral Maturation (CVM) method in a group of indigenous
      Australians and to relate the ossification events to the timing of peak growth in
      both stature and the mandible. Data were obtained from longitudinal records of 74
      Australian Aboriginal children living at Yuendumu Settlement in the Northern
      Territory of Australia. CVM stages were limited to particular growth periods: in
      a large percentage of subjects stage 1 occurred in the pre-peak period of growth,
      stages 2 and 3 in the peak period, and stages 4 and 5 in the post-peak period.
      Our findings were similar to those reported in other ethnic groups, suggesting
      that they can be applied more generally in orthodontic practice to assess a
      child's growth activity. In the majority of boys, CVM stage 2 would appear to be
      a good time to commence an orthopaedic phase of treatment, whereas in girls,
      results would support an earlier more cautious approach, sometime before stage 2
      is reached. Peak growth occurs between stages 2 and 3 and timing is extremely
      important to maximize the effects of growth in the treatment process.

PMID- 12790354
TI  - Minimizing publication bias.

PMID- 12790355
TI  - PET studies in dementia.
AB  - Measurement of local cerebral glucose metabolism (lCMRGlc) by positron emission
      tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard
      technique during the past 20 years and is now available at many university
      hospitals in all highly developed countries. Many studies have documented a close
      relation between lCMRGlc and localized cognitive functions, such as language and
      visuoconstructive abilities. Alzheimer's disease (AD) is characterized by
      regional impairment of cerebral glucose metabolism in neocortical association
      areas (posterior cingulate, temporoparietal and frontal multimodal association
      cortex), whereas primary visual and sensorimotor cortex, basal ganglia, and
      cerebellum are relatively well preserved. In a multicenter study comprising 10
      PET centers (Network for Efficiency and Standardisation of Dementia Diagnosis,
      NEST-DD) that employed an automated voxel-based analysis of FDG PET images, the
      distinction between controls and AD patients was 93% sensitive and 93% specific,
      and even in very mild dementia (at MMSE 24 or higher) sensitivity was still 84%
      at 93% specificity. Significantly abnormal metabolism in mild cognitive deficit
      (MCI) indicates a high risk to develop dementia within the next two years.
      Reduced neocortical glucose metabolism can probably be detected with FDG PET in
      AD on average one year before onset of subjective cognitive impairment. In
      addition to glucose metabolism, specific tracers for dopamine synthesis (18F-F
      DOPA) and for (11C-MP4A) are of interest for differentiation among dementia
      subtypes. Cortical acetylcholine esterase activity (AChE) activity is
      significantly lower in patients with AD or with dementia with Lewy bodies (DLB)
      than in age-matched normal controls. In LBD there is also impairment of dopamine
      synthesis, similar to Parkinson disease.

PMID- 12790356
TI  - Quantitative evaluation by Tl-201 scintigraphy in the diagnosis of thyroid
      follicular nodules.
AB  - We examined the diagnostic capability of a quantitative evaluation by determining
      the optimum area for comparisons with nodule and optimum imaging time by Tl-201
      scintigraphy in thyroid follicular nodules, retrospectively. Ninety-one thyroid
      follicular nodules, for which the pathological diagnosis had been established,
      were examined (60 benign, 31 malignant). After 74 MBq of Tl-201 chloride was
      injected intravenously, Tl-201 scintigrams were obtained at 10, 20, 30, and 120
      min. For the quantitative evaluation, the area with the greatest accumulation in
      the nodule and a comparative region in the contralateral thyroid and the soft
      tissues in the cervical region were manually selected as the region of interest
      (ROI) referring to Tc-99m pertechnetate scintigrams and ultrasonographic findings
      as a guide by two radiologists, and the T/N ratio (tumor/normal tissue ratio) and
      T/S ratio (tumor/soft tissue ratio) were calculated. The pixel counts were
      determined for all ROI. A summary index of overall test performance can be
      calculated as the area under the receiver operating characteristic (ROC) curve
      (Area (Az)), and the likelihood ratios were also calculated. We estimated the cut
      off on a fitted binormal ROC curve. Multiple regression analyses were used to
      investigate the relationships between the optimum quantitative evaluation and 5
      independent variables. A p value below 5% was considered to be significant. The
      T/N ratio and T/S ratio were significantly higher in the malignant group at 10
      min (0.844 and 0.702), 20 min (0.844 and 0.704), 30 min (0.841 and 0.670), and
      120 min (0.887 and 0.733), respectively (p < 0.01). The Az for the T/N ratio was
      greatest at 120 min. The multiple regression analysis showed that only 'benign or
      malignant' was a significant variable in the T/N ratio at 120 min. It correlated
      significantly in interobserver (r = 0.80) and intraobserver (r = 0.80) studied (p
      < 0.001). An assessment of the cut-off value of the T/N ratio at 120 min, at the
      cut-off of 1.255, the likelihood ratio for positive test result was greatest at
      8.56, while at the cut-off of 1.010, the likelihood ratio for negative test
      result was lowest at 0.165. The T/N ratio at 120 min was more useful than the
      other condition to distinguish between benign and malignant thyroid follicular
      nodules.

PMID- 12790357
TI  - Dependency of energy and spatial distributions of photons on edge of object in
      brain SPECT.
AB  - OBJECTIVES: Accurate mu maps are important for quantitative image reconstruction
      in SPECT. The Compton scatter energy window (CSW) technique has been proposed to
      define the outline of objects. In this technique, a lower energy window image is
      acquired in addition to the main photo-peak energy window. The image of the lower
      energy window is used to estimate the edge of the scanned object to produce a
      constant attenuation map. The aim of this study was to investigate the dependency
      of CSW on the spatial and energy distribution of radioisotope to predict the
      edges of objects. METHODS: Two particular cases of brain study were considered,
      namely uniform distribution and non-uniform distribution using Monte Carlo
      simulation and experiments with uniform cylindrical phantom and hotspot phantom.
      The phantoms were filled with water and a radioactive solution of 99mTc. For each
      phantom, 20%, 30%, 40% and 50% thresholds of the mean profile were applied to
      estimate Ewt, the energy window for minimum difference between the estimated and
      true edge of objects. RESULTS: The Ewt's were 100-120 keV with a 40% threshold
      and 92-114 keV with a 30% threshold for uniform and hotspot phantoms,
      respectively. CONCLUSIONS: Edge of the objects with CSW technique varies with
      energy window and thresholds. Careful setting of the energy window is required to
      use the CSW technique.

PMID- 12790358
TI  - Tc-99m-HMPAO uptake by bronchoalveolar cells.
AB  - Lung uptake of intravenously injected Tc-99m-HMPAO is observed in smokers and in
      lung toxicity due to various agents. We investigated the Tc-99m-HMPAO uptake of
      bronchoalveolar lavage (BAL) cells in the lungs after incubation in in vitro
      conditions (6 patients), intravenous injection (IV) (7 patients) and inhalation
      (INH) (6 patients) of Tc-99m-HMPAO in order to show whether BAL cells are also
      responsible for Tc-99m-HMPAO uptake in the lungs. Cell/supernatant (C/S) count
      ratio was 7.0 +/- 3.5, 29.3 +/- 40.8 and 8.4 +/- 4.5 for in vitro, IV and INH
      groups, respectively. C/Sin vitro showed a positive correlation with % alveolar
      macrophages (r = 0.943, p = 0.0048) and a negative correlation with % neutrophils
      (r = -0.945, p = 0.0045). Cells/whole BAL fluid ratio correlated with the amount
      of daily cigarette consumption in INH group (r = 0.95, p = 0.0037). Tc-99m-HMPAO
      showed adherence to mucus after inhalation. Tc-99m-HMPAO diffuses into alveolar
      spaces after injection and is present in BAL fluid and BAL cells both after
      injection and inhalation. Glutathione concentration and oxido-reductive state of
      the epithelial lining fluid and BAL cells may influence the lung uptake of Tc-99m
      HMPAO.

PMID- 12790359
TI  - Disseminated Mycobacterium avium complex (MAC) in a patient with acquired
      immunodeficiency syndrome (AIDS).

PMID- 12790360
TI  - Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin
      myocardial SPECT--comparison with acute coronary syndrome.
AB  - We assessed Takotsubo (ampulla) cardiomyopathy compared with acute coronary
      syndrome (ACS) using two-dimensional echocardiography and 99mTc-tetrofosmin
      myocardial SPECT. METHODS: We examined 10 patients with Takotsubo cardiomyopathy
      and 16 with ACS at the time of emergency admission (acute phase), at three to
      nine days after the attack (subacute phase) and at one month after the attack
      (chronic phase). The left ventricle was divided into nine regions on
      echocardiograms and SPECT images, and the degree of abnormalities in each region
      was scored in five grades from normal (0) to severely abnormal (4). RESULTS:
      Coronary angiography revealed total or subtotal occlusion in patients with ACS
      but no stenotic legions in those with Takotsubo cardiomyopathy. The amount of ST
      segment elevation (mm) was 7.9 +/- 3.4 in patients with Takotsubo cardiomyopathy
      and 7.3 +/- 3.7 in those with ACS (N.S.). Abnormal wall motion scores on
      echocardiograms were 13.8 +/- 4.4, 4.4 +/- 3.8 and 1.8 +/- 2.3 during the acute,
      subacute and chronic phases in patients with Takotsubo cardiomyopathy, and 13.9
      +/- 4.0, 11.7 +/- 3.7, 7.6 +/- 4.2, respectively in patients with ACS. The value
      of MB fraction of creatine phosphokinase (IU/l) was 34 +/- 23 in patients with
      Takotsubo cardiomyopathy and 326 +/- 98 in those with ACS (p < 0.001). Abnormal
      myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.4 +/-
      3.2, 3.2 +/- 3.3 and 0.7 +/- 1.1 during the acute, subacute and chronic phases
      respectively, in patients with Takotsubo cardiomyopathy, and 15.8 +/- 4.1, 13.5
      +/- 4.4, 8.2 +/- 4.4, respectively, in those with ACS. The numbers of myocardial
      segments that did not uptake 99mTc-tetrofosmin during the acute phase were 0.5 +/
      0.8 and 3.6 +/- 2.8 in patients with Takotsubo cardiomyopathy and ACS,
      respectively. CONCLUSION: Impaired coronary microcirculation might be a causative
      mechanism of Takotsubo cardiomyopathy.

PMID- 12790361
TI  - Effect of sabcomeline on muscarinic and dopamine receptor binding in intact mouse
      brain.
AB  - Sabcomeline [(R-(Z)-(+)-alpha-(methoxyiamino)-1-azabicyclo[2.2.2]octane-3
      acetonitrile)] is a potent and functionally selective muscarinic M1 receptor
      partial agonist. However, little is known of the binding properties of
      sabcomeline under in vivo conditions. In this study, muscarinic receptor
      occupancy by sabcomeline in mouse brain regions and heart was estimated using
      [3H]quinuclidinyl benzilate (QNB) and [3H]N-methylpiperidyl benzilate (NMPB) as
      radioligands. In the cerebral cortex, hippocampus, and striatum, the estimated
      IC50 value of sabcomeline for [3H]NMPB binding was almost 0.2 mg/kg. Sabcomeline
      was not a selective ligand to M1 receptors as compared with biperiden in vivo. In
      the cerebral cortex, maximum receptor occupancy was observed about 1 hr after
      intravenous injection of sabcomeline (0.3 mg/kg), and the binding availability of
      mACh receptors had almost returned to the control level by 3-4 hr. These findings
      indicated that the binding kinetics of sabcomeline is rather rapid in mouse
      brain. Examination of dopamine D2 receptor binding revealed that sabcomeline
      affected the kinetics of both [3H]raclopride and [3H]N-methylspiperone (NMSP)
      binding in the striatum. It significantly decreased the k3 and k4 of
      [3H]raclopride binding resulting in an increase in binding potential (BP = k3/k4
      = Bmax/Kd) in sabcomeline-treated mice, and an approximately 15% decrease in k3
      of [3H]NMSP binding was also observed. Although the mechanism is still unclear,
      sabcomeline altered dopamine D2 receptor affinity or availability by modulations
      via neural networks.

PMID- 12790362
TI  - Monitoring of response to radiation therapy for human tumor xenografts using
      99mTc-HL91 (4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime).
AB  - PURPOSE: Oxygenation status of tumor tissue is an important factor to
      discriminate it with respect to its radiosensitivity. 99mTc-4,9-diaza-3,3,10,10
      tetramethyldodecan-2,11-dione dioxime (99mTc-HL91) is retained in hypoxic
      tissues, making it possible to use it as hypoxic imaging agent. We evaluated if
      the accumulation of 99mTc-HL91 in tumors could aid in the prediction of
      sensitivity of radiation therapy of cancers. METHODS: Human tumors (the gastric
      cancer cell line: MKN45, the epidermoid carcinoma cell line: KB-31, and the lung
      adenocarcinoma cell line: HLC) were xenografted into the thigh of athymic mice
      and irradiated with a 4 MV linear accelerator. Tumor growth was measured and
      99mTc-HL91 uptakes in tumors were determined by serial imaging, biodistribution,
      and autoradiography. RESULTS: 99mTc-HL91 uptake (ratio of ROItumor to ROIwhole
      body) in HLC ranged from 1.1 to 8.0%, and it did not show any response to
      radiation therapy. Major variations were observed in 99mTc-HL91 accumulation in
      MKN45 and KB-31; from 0.7 to 4.7%, and from 1.0 to 7.3%, respectively. Some
      tumors responded to radiotherapy, while others did not. Tumor response was not
      dependent on the 99mTc-HL91 uptake, tumor size or radiation dose. Comparing 99mTc
      HL91 uptake in tumors before (B) and after (A) their radiation, uptake (B) was
      always smaller than uptake (A) for HLC, and they did not respond to irradiation
      at all. For MKN45 and KB-31, tumors responded to radiation when their uptake (A)
      was not higher than uptake (B). In contrast, the tumors continued to grow when
      their uptake (A) was higher than uptake (B). Sequential 99mTc-HL91 imaging of KB
      31 and their autoradiography indicated that tumors whose 99mTc-HL91 uptakes was
      increased post irradiation were composed of mainly hypoxic cells. On the other
      hand, many viable areas were observed in tumors when the increase in 99mTc-HL91
      uptake was relatively small. CONCLUSION: 99mTc-HL91 uptake in tumors did not
      always relate to their sensitivities to radiation therapy. Sequential 99mTc-HL91
      imagings post irradiation showed that the increase in 99mTc-HL91 uptake in tumors
      predicted a poor response to radiation therapy, and that a decrease or no change
      suggested that radiation therapy would be effective. Monitoring by 99mTc-HL91
      imaging is a good tool to predict the radiosentivities of tumors.

PMID- 12790363
TI  - Acetazolamide assisted Tc-99m MAG3 renography to assess renal blood flow reserve.
AB  - OBJECTIVE: The present study examines whether or not baseline and acetazolamide
      (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. METHODS:
      Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m
      MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ
      renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney
      and the percentage change in cERPF of those parameters (deltaERPF) were obtained
      before and after the administration of ACZ in 10 subjects without hypertension or
      diabetes (normal group), in 10 with essential hypertension (hypertensive group)
      and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo
      test was performed in the 10 without hypertension or diabetes using distilled
      water instead of ACZ (placebo group). RESULTS: The placebo test performed in the
      10 without hypertension or diabetes using distilled water instead of ACZ
      indicated that the parameter variance between the two types of renogram was below
      3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the
      normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89
      +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and
      24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in
      the cERPF value was significant in the normal and hypertensive groups whereas
      this did not change in the diabetic group before or after ACZ administration.
      CONCLUSIONS: We suggested that the deltaERPF determined by baseline and ACZ Tc
      99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.

PMID- 12790364
TI  - Stripe sign in pulmonary embolism: a review of the causes.
AB  - The most common indication for radionuclide imaging of lungs is the evaluation of
      suspected pulmonary thromboembolism (PE). Scintigraphically PE classically
      produces ventilation/perfusion mismatch, that is perfusion defects in areas
      showing normal ventilation. Stripe sign refers to the visualization a stripe at
      normally perfused lung interposed between a defect and adjacent pleural surfaces
      as originally described by Gottschalk. In the present case the authors describe a
      patient with a ventilation/perfusion scan suggesting PE. She also had a stripe
      sign on the perfusion scan with normal ventilation. On the follow-up perfusion
      scintigraphy, normal perfusion was seen in the corresponding area. The literature
      on stripe sign is also reviewed.

PMID- 12790365
TI  - Bartter's syndrome and captopril scintigraphy: a case report.
AB  - We report a case of a woman who came to our attention because of hypokalemia,
      hyperreninemia and hyperaldosteronemia but with normal blood pressure. Under
      suspicion of a normotensive renal artery stenosis captopril and baseline
      scintigraphies were performed. Captopril scintigraphy demonstrated a bilateral
      progressive retention of radiopharmaceutical without significant excretion. The
      baseline study revealed a complete normalization of the scintigraphyc picture. A
      Magnetic Resonance Angiography (Angio-MRI) performed to evaluate renal arteries
      gave completely normal results. On the basis of the clinical picture and imaging
      findings a diagnosis of Bartter's syndrome was formulated. Renal function in
      Bartter's syndrome patients is maintained by hyperactivation of the renin
      angiotensin system. Acute administration of captopril in these patients induces
      an increase of renal plasma flow whereas it has no effects on glomerular
      filtration rate thus inducing a decrease of the filtration fraction: post
      captopril renal scintigraphy of our patient depicted exactly this feature.
      Although the diagnosis of Bartter's syndrome is based on the clinical picture and
      biochemical abnormalities, scintigraphic tests could be useful in differentiating
      Bartter's syndrome from other causes of hypokalemia.

PMID- 12790366
TI  - Tc-99m-tetrofosmin scintigraphy in a primary giant cell tumor of bone with
      pulmonary metastases.
AB  - Giant cell tumor (GCT) is usually considered to be a benign entity. In rare
      cases, pulmonary metastases can be observed. This report documents the 99mTc
      tetrofosmin scan findings of a conventional GCT of the femur and developed
      pulmonary nodules. The lung lesions were felt to be an example of benign
      metastases. According to our review, this is the first case in the literature
      demonstrating tetrofosmin accumulation in a GCT of bone and its pulmonary
      metastases.

PMID- 12790367
TI  - A splenic pseudotumor: an accessory spleen.
AB  - We encountered a case of splenic pseudotumor. It contained a cystic portion, and
      the solid portion of the mass showed much higher vascularity than the proper
      spleen on dynamic CT. An accessory spleen was considered most likely, but the
      differential diagnosis still included malignant lymphoma and metastatic tumor.
      The diagnosis was obtained by technetium-99m Sn colloid scintigraphy.

PMID- 12790368
TI  - Scintigraphic prediction of therapeutic outcomes of splenectomy in patients with
      thrombocytopenia.
AB  - In patients with thrombocytopenia, platelet scintigraphy has been used to locate
      the site of platelet sequestration and destruction and to determine whether
      splenectomy will be of benefit. However, its efficacy in predicting the outcome
      of splenectomy is controversial. We assessed the feasibility of platelet
      scintigraphy in this regard. METHODS: Platelet scintigraphy was performed in five
      patients (2 women, 3 men, mean age 48 years) before splenectomy. Four patients
      were diagnosed with idiopathic thrombocytopenic purpura and one with
      hypersplenism due to portal hypertension caused by intrahepatic chemotherapy
      against metastatic liver tumors of rectal cancer. Platelets labeled with 37 MBq
      of In-111 oxine or 1110 MBq of Tc-99m HMPAO were intravenously injected. Anterior
      images were obtained with a gamma camera 3-5 and 23-29 hours post-injection in
      five patients. Additional images were obtained 48 hours post-injection in three
      patients. For the analysis, a spleen/liver ratio (S/L ratio) was calculated using
      mean counts in regions of interest defined on the spleen and the liver. Serum
      platelet counts were measured before and after the operation; in three patients,
      splenectomy effectively resolved the thrombocytopenia (Group A), while it was
      ineffective in two patients (Group B). RESULTS: The S/L ratios were apparently
      higher in Group A than in Group B; in Group A, the ratios were 6.05, 6.97 and
      3.16 at 3-5 hours, 12.67, 7.48 and 3.46 at 23-29 hours and 17.66 and 8.12 at 48
      hours, whereas, in Group B, they were 0.67 and 0.66 at 3-5 hours, 0.52 and 0.54
      at 24 hours, and 0.42 at 48 hours. CONCLUSION: The results of this study indicate
      that platelet scintigraphy is of value in predicting the therapeutic efficacy of
      splenectomy in patients with thrombocytopenia.

PMID- 12790369
TI  - The importance of polyvinyl chloride in medical devices and the physician's role
      in the choice of materials.

PMID- 12790370
TI  - How to control blood glucose under continuous glucose challenge.
AB  - A newly improved method for controlling blood glucose was compared with the
      standard model predictive controller under continuous glucose infusion.
      Continuous intravenous glucose infusion at rates of 50 or 100 mg/kg/hour was
      conducted on pancreatectomized dogs. An improved blood glucose control method
      using a combination of the proportional controller in the initial stage and the
      model predictive controller in the later stage was compared with the simple model
      predictive controller. The parameters of the controller were determined by
      identifying individual responses to the infused insulin during the first 60
      minutes. The parameters of the proportional controller were changed at 60, 90,
      and 120 minutes to reflect the response to the infused insulin. The simple model
      predictive controller was able to reach the target level in the usual manner
      under the low infusion rate of glucose. However, under glucose infusion rates of
      100 mg/kg/hour and more, it was difficult to reach the target level within 8
      hours. In contrast, the improved system could reach the target level within 5 to
      8 hours even under continuous glucose challenge. Addition of the modified
      proportional controller to the model predictive controller can stabilize the
      blood glucose control even under continuous glucose infusion.

PMID- 12790371
TI  - The National Cardiovascular Center electrohydraulic total artificial heart and
      ventricular assist device systems: current status of development.
AB  - Electrohydraulic total artificial heart (EHTAH) and electrohydraulic ventricular
      assist device (EHVAD) systems have been developed in our institute. The EHTAH
      system comprises a pumping unit consisting of blood pumps and an actuator, as
      well as an electronic unit consisting of an internal controller, internal and
      external batteries, and transcutaneous energy transfer (TET) and optical
      telemetry (TOT) subunits. The actuator, placed outside the pericardial space,
      reciprocates and delivers hydraulic silicone oil to the alternate blood pumps
      through a pair of flexible oil conduits. The pumping unit with an external
      controller was implanted in 10 calves as small as 55 kg. Two animals survived for
      more than 12 weeks in a good general condition. The assumed cardiac output ranged
      between 6 and 10 L/min, the power consumption was 12-18 W, and the energy
      efficiency was estimated to be 9-11%. Initial implantation of subtotal system
      including electronic units was further conducted in another calf weighing 73 kg.
      It survived for 3 days with a completely tether free system. The EHVAD system is
      developed by using the left blood pump and the actuator of the EHTAH, which were
      packaged in a compact metal casing with a compliance chamber. In vitro testing
      demonstrated maximum output more than 9 L/min and more than 13% maximum
      efficiency. The initial animal testing lasted for 25 days. These results indicate
      that our EHTAH and EHVAD have the potential to be totally implantable systems.

PMID- 12790372
TI  - Volume controlled apparatus for neonatal tidal liquid ventilation.
AB  - Conventional gas ventilation is often unsuccessful for premature neonatal
      patients suffering from respiratory distress syndrome (RDS). For such patients,
      liquid ventilation (LV) with perfluorocarbon (PFC) liquids has been proposed. By
      eliminating the air-liquid interface in saccules (the premature gas exchange
      structures), where scarce or absent surfactant production exists, pulmonary
      instability is avoided, lung compliance is improved, and atelectatic saccules are
      recruited, ultimately lowering the saccular pressure. Tidal LV involves
      administrating a liquid tidal volume to the patient at each respiratory cycle,
      and therefore requires a dedicated circuital setup to deliver, withdraw, and
      refresh the PFC during the treatment. We have developed a prototype liquid
      breathing system (LBS). The apparatus comprises two subcircuits managed by a
      personal computer based control system. The ventilation subcircuit performs
      inspiration/expiration with two sets of peristaltic pumps. A system to evaluate
      the true inspired/expired volumes was devised that consists of two reservoirs
      equipped with pressure transducers measuring the hydraulic head of the fluid
      therein. Volume accuracy was +/- 0.3 ml. The refresh subcircuit properly
      processes the PFC by performing filtration (DFA, Pall, NY), oxygenation, CO2
      scavenge, and heat exchange (SciMed 2500, Life Systems, MN). The new apparatus
      has been used in preliminary animal tests on five newborn mini pigs with induced
      acquired RDS. The PFC used was RM-101 (Miteni, Milano, Italy). The animals were
      successfully supported for 4 hours each. Mean arterial O2 pressure was 131.4 mm
      Hg (range 79.0-184.2), and mean arterial CO2 pressure was 64.8 mm Hg (range 60.0
      73.4).

PMID- 12790373
TI  - Operating point control system for a continuous flow artificial heart: in vitro
      study.
AB  - We proposed and developed a practical and effective servo control system for
      rotary blood pumps. A rotary blood pump for assisting the failing natural heart
      should be operated only in physiologically acceptable conditions. The operation
      of a rotary blood pump is based on the rotational speed of the impeller and
      pressure head. If the pump flow and the pressure head are set within an
      acceptable range, the driving condition is deemed normal condition, and this
      control system maintains the preset operating point by applying proportional and
      detective control (PD control). If the pump flow or pressure head is outside the
      acceptable range, the driving condition is determined to be abnormal condition,
      and this system operates the pump in a recovery fashion. If the driving condition
      is kept under abnormal conditions of sudden decrease of the flow, the condition
      is termed a suction condition. The controller releases the pump from the suction
      condition and later returns it to the normal condition. In this study, we
      evaluated these servo control modes of the centrifugal pump and confirmed whether
      the performance of this proposed operating point control system was practical.

PMID- 12790374
TI  - Development of built-in type and noninvasive sensor systems for smart artificial
      heart.
AB  - It is very important to grasp the artificial heart condition and the physiologic
      conditions for the implantable artificial heart. In our laboratory, a smart
      artificial heart (SAH) has been proposed and developed. An SAH is an artificial
      heart with a noninvasive sensor; it is a sensorized and intelligent artificial
      heart for safe and effective treatment. In this study, the following sensor
      systems for SAH are described: noninvasive blood temperature sensor system,
      noninvasive blood pressure sensor system, and noninvasive small blood flow sensor
      system. These noninvasive sensor systems are integrated and included around the
      artificial heart to evaluate these sensor systems for SAH by the mockup
      experiments and the animal experiments. The blood temperature could be measured
      stably by the temperature sensor system. Aortic pressure was estimated, and
      sucking condition was detected by the pressure sensor system. The blood flow was
      measured by the flow meter system within 10% error. As a result of these
      experiments, we confirmed the effectiveness of the sensor systems for SAH.

PMID- 12790375
TI  - Bound solute dialysis.
AB  - We used the thermodynamic principles governing bound solute dialysis, commonly
      referred to as "albumin dialysis" or "sorbent dialysis" and practiced clinically
      with the Molecular Adsorbent Recirculating System (MARS) and Biologic-DT
      approaches, respectively, to develop a comprehensive understanding of the
      process. Dimensionless parameters emerging from the thermodynamic analysis that
      govern bound solute dialysis are as follows: (1) lambda, the binding power of the
      solute binding moiety; (2) kappa, the dialyzer mass transfer/blood flow rate
      ratio; (3) alpha, the dialysate/blood flow rate ratio; (4) beta, the
      dialysate/blood binding moiety concentration ratio, and (5) psi, the
      solute/binding moiety concentration ratio in the blood. Results from a
      mathematical model of countercurrent bound solute dialysis for phi = 0.9 indicate
      that for a given binding moiety (fixed lambda), the most important parameter for
      achieving high removal rates is the dialyzer mass transfer ratio for free
      (unbound) solute. The results also show solute removal approaching an asymptote
      with increasing beta that is dependent on kappa and independent of alpha. More
      importantly, results indicate that once a dialysis membrane is chosen, solute
      removal is virtually independent of blood flow rate, dialysate flow rate, and
      amount of binding moiety in the dialysate, provided the amount is greater than
      approximately 90% of that required to reach the asymptote. Experimental
      observations over a range of blood flow rates (100-400 ml/ minute), dialysate
      flow rates (50-400 ml/minute), and dialysate/blood albumin concentration ratios
      (beta = 0-0.3) corroborate the model predictions and indicate that < 4 g/L
      albumin in the dialysate solution is required for effective bound solute
      dialysis. The experimental results also show evidence of enhanced mass transfer
      once the dialysis membrane pore structure surface saturates with albumin.

PMID- 12790376
TI  - Hypoalbuminemia is a marker of overhydration in chronic maintenance patients on
      dialysis.
AB  - Hypoalbuminemia is an important risk factor for increased morbidity and mortality
      in patients on dialysis. Hypoalbuminemia is usually attributed to malnutrition or
      a state of chronic inflammation. However, hypoalbuminemia could result from
      hemodilution caused by chronic volume expansion. We prospectively evaluated 142
      patients on chronic dialysis for 12 consecutive months (mean age: 62 +/- 14
      years; 41% women, 37% African American, 43% diabetic, 27% peritoneal dialysis).
      Intracellular (ICW) and extracellular (ECW) water content was estimated using
      single frequency bioelectrical impedance. Values in each albumin grouping (group
      1, < 3.5 g/dl; group 2, 3.5-4.0 g/dl; group 3, > 4.1 g/dl) are expressed as
      annual mean +/- SEM. Group 1 patients had lower body weight, body mass index,
      blood urea nitrogen, serum creatinine, dietary protein intake, and ICW content
      than those in groups 2 and 3. ECW was significantly increased in group 1 when
      compared with groups 2 and 3 (p < 0.001). A significant correlation was found
      between ECW and serum albumin concentration (R = 0.2230; p < 0.0001). Resistance
      and reactance were decreased in group 1 when compared with groups 2 and 3 (p <
      0.05 and 0.001, respectively), causing the resultant bioimpedance vector to move
      away from the normal population range into the overhydration boundaries. We
      conclude that, in addition to malnutrition and chronic inflammation,
      overhydration is a contributor to hypoalbuminemia in patients on chronic
      dialysis.

PMID- 12790378
TI  - Clinical biodurability of aliphatic polyether based polyurethanes as peritoneal
      dialysis catheters.
AB  - Thermoplastic polyurethane elastomers are the most important implantable grade
      polyurethanes in medical applications. An aliphatic polyether based polyurethane,
      Tecoflex (TF; Thermedics, Inc., Woburn, MA), is used in the construction of a
      proprietary peritoneal dialysis (PD) catheter. Information is limited regarding
      the biostability of the TF polymer in the clinical environment as a PD catheter.
      This report presents the clinical experience regarding the biodurability of 104
      catheter implants. The extracorporeal tubing segments of all TF catheters
      eventually developed aesthetically offensive discoloration, opaqueness, and
      surface tackiness. Catheter breaks in the external segment occurred in 27% of
      devices that survived longer than 28 months. Mupirocin ointment at the catheter
      skin exit site caused swelling and deformity of the TF in one case. Three
      catheters extruded as a result of Dacron cuffs separating from the tubing wall.
      Catheters removed for other reasons were frequently found to have loose cuffs,
      especially if the devices were implanted for several years. Causes and possible
      mechanisms for observed failures are discussed. The durability of biomaterials
      used in construction of PD catheters is of vital importance for successful long
      term functioning. The TF polymer embodied as a PD catheter represents a mismatch
      of the material and its mission. Fabrication of PD catheters from higher grade
      polyurethanes possessing greater biostability should be explored. Silicone rubber
      appears to remain the most durable material to date for PD catheter construction.

PMID- 12790377
TI  - Heparin solution locked in acute hemodialysis catheters: impact on activated
      partial thromboplastin time.
AB  - Fifteen patients on hemodialysis, wearing acute dual lumen hemodialysis catheters
      (DLHCs) locked with a 4 ml heparin solution (HS) containing 7,500 IU of
      conventional heparin (3,750 IU/lumen), were studied. After the preexisting HS was
      aspirated and discarded, 10 ml of blood was withdrawn from each lumen in a
      syringe. Then, two 3 ml blood samples (A and B) were withdrawn in a row from the
      venous lumen; a third blood sample (C) was withdrawn from a peripheral vein, and
      the 20 ml of blood in the syringe was returned to the patient. Patient to control
      ratios of activated partial thromboplastin time (aPTT) in samples A, B, and C
      were 2.87 +/- 1.04, 2.02 +/- 0.85, and 1.06 +/- 0.14, respectively (p < 0.002
      comparing A to B and B to C). In these patients, we also studied the effect of
      the same HS on the aPTT, 10 minutes after the filling of the DLHCs postdialysis.
      A blood sample (H1) was withdrawn at the end of the session; 10 minutes after
      injecting each lumen of the DLHC with a 2 ml HS containing 3,750 IU of heparin, a
      second blood sample (H2) was drawn from a peripheral vein. The aPTT ratios in
      samples H1 and H2 were 1.15 +/- 0.13 and 3.58 +/- 0.61 respectively (p < 0.0001).
      We concluded that even after the aspiration of 15 ml from the venous lumen of a
      DLHC filled with a 2 ml HS containing 3,750 IU of heparin, the next blood sample
      remains contaminated by heparin. Filling each lumen of a DLHC with the same HS
      results in a significant increment of the aPTT 10 minutes later.

PMID- 12790380
TI  - High vacuum drainage of the chest using a miniature double lumen chest tube.
AB  - The purpose of this study was to test the safety and efficacy of a high vacuum
      pressure drainage system with a 7F double lumen chest tube. Methods included
      animal experiments, where seven rabbits were subjected to bilateral tube
      thoracostomies, using a 7F double lumen chest tube at 340 torr on one side and
      more than 500 torr on the other for 30 minutes. Then, a preliminary clinical
      study was done. Three patients were treated with a 7F double lumen chest tube and
      a vacuum box at 340 torr after a thoracoscopic sympathectomy for approximately 60
      minutes. An additional 460 patients were treated with a conventional system,
      using a 20F single lumen chest tube and chest drainage system at 14.7 torr
      following the same operation. All animals tolerated the test well. Suction injury
      of the lung was noted on the control side. In the clinical study, the air leaks
      stopped within 15 minutes, and no patients showed a radiologic sign of lung
      suction injury. Six patients in the control group developed subcutaneous
      emphysema. In conclusion, high vacuum pressure drainage of the chest using the 7F
      double lumen chest tube is safe and effective.

PMID- 12790379
TI  - Paraoxonase activity and paraoxonase 1 gene polymorphism in patients with uremia.
AB  - Patients on hemodialysis (HD) show an increased risk for developing
      atherothrombotic events. The oxidative modification of low density lipoproteins
      (LDL) play an important role in the pathogenesis of atherosclerosis. In patients
      with uremia (chronic renal failure and HD), the increased oxidative stress
      induces oxidative modification of LDL. High density lipoproteins (HDL) exhibit a
      double antiatherogenic role, removing both lipid peroxides from LDL and
      cholesterol from tissues or vascular wall. Paraoxonase 1 (PON1) is one of three
      enzymes shown to prevent the formation of oxidized LDL. PON1 activity is
      modulated by its genetic polymorphism and by non-genetic factors, such as diet,
      smoking, acute phase reactants, and hormones. PON1 activity has been found to be
      significantly decreased in uremia. The present study aimed to verify the
      possibility that this reduced activity could be caused by a different PON1 gene
      polymorphism between patients on HD and healthy subjects, but this was not the
      case. The main cause may be identified in the different distribution of HDL
      subspecies, rather than in the different PON1 allele distribution between healthy
      subjects and patients with uremia.

PMID- 12790381
TI  - A new approach to detection of the cavitation on mechanical heart valves.
AB  - The cavitation on the mechanical heart valves (MHVs) is thought to be a cause of
      the mechanical failure of the occluder; also, the free radicals that would be
      generated when the cavitation bubbles implode might affect the patients
      chemically. These cavitation effects are attributed to the bubble collapse.
      Therefore, it is important to detect the bubble implosion behavior to analyze the
      cavitation on MHVs. The cavitation bubbles induce the generation of free radicals
      at their implosion, and the excited hydroxyl radicals emit the faint light. Based
      on this fact, we have tried to observe the faint light emission from a MHV to
      specifically capture the implosion of the cavitation bubbles. A highly sensitive
      CCD (charge coupled device) camera (C2400-35 VIM camera, Hamamatsu Photonics,
      Hamamatsu, Japan) was adopted in this study. This camera can observe low light
      down to the single photon counting range, and it gives two-dimensional mapping of
      the light. A 20 mm Bjork-Shiley valve was submerged in the water tank of 10 L
      deionized water with luminol as a light enhancer, and then the pressure
      difference of 150 mm Hg was exerted on the valve at a rate of 60 bpm with a pulse
      duplicator. The camera and the water tank were settled in the lightproof
      configuration. After 2 hours of exposure, faint light images have been obtained
      successfully. The light emits mostly from the edge of the occluder on the inflow
      side in the major orifice of the valve. Therefore the results suggest that the
      bubbles would implode around this region and that free radicals caused by
      cavitation might be produced on MHV, which has coincided with our preliminary
      result by an electron spin resonance spectrometry.

PMID- 12790382
TI  - HeartPatch implanted direct cardiac compression: effect on coronary flow and flow
      patterns in acute heart failure sheep.
AB  - A novel HeartPatch direct cardiac compression (DCC) device has been shown to
      effectively restore circulatory parameters in sheep with acute heart failure
      (HF). Its effect on the coronary circulation and myocardial perfusion, however,
      remains uncertain. The effect of DCC assist on coronary artery blood flow (CABF)
      and its patterns in acute HF sheep were examined in this study. Ten sheep (51 +/-
      6 kg) were implanted with a heart patch on each of the left ventricular and right
      ventricular free walls 1 week before study. Stable HF [cardiac output (CO) at 51
      +/- 8% of baseline] induced by intravenous esmolol resulted in CABF decreasing to
      53 +/- 16% of baseline (p < 0.001). DCC device activation did not alter CABF (54
      +/- 15% of baseline, N.S.) but was accompanied by increases in both peak
      antegrade and retrograde flow velocity (161 +/- 75%, p < 0.001 and 413 +/- 377%,
      p < 0.001). A shift in the proportion of flow occurring in diastole (%DF) also
      was observed: baseline, 81 +/- 9%; HF, 82 +/- 6%; DCC assist, 121 +/- 16% (p <
      0.001). Despite significant changes in coronary artery flow pattern resulting
      from DCC of the failing heart, total antegrade coronary flow was maintained.
      These findings suggest that myocardial perfusion is not compromised by DCC.

PMID- 12790383
TI  - A durable load bearing muscle to prosthetic coupling.
AB  - Skeletal muscles have been successfully linked to power mechanical support
      devices acutely. However, the required load bearing muscle to prosthetic
      interfaces have not been consistently durable. Tissue simply may not tolerate the
      repetitive pressure generated, ranging to 40,000 mm Hg, when necessary forces
      meet the crosssectional areas accessible by suture or clamp fixation.
      Dramatically increasing the force transfer surface by dispersing ultrafine
      polymer fibers in the distal muscle substance is the principle of a coupling
      device termed the MyoCoupler. Earlier, effective force transfer was
      computationally projected and confirmed in a pilot 30 day rabbit trial, with pull
      out strength several times need. This investigation tested bonding strength after
      longer periods and examined the postulated fiber tissue integration. Devices and
      controls (buttressed suture fixation alone) were implanted contralaterally in the
      posterior tibial muscles of 28 rabbits for up to 90 days. Of the 28 rabbits, 21
      were used for bond strength testing, and 3 were used for histology. Infection or
      procedural error disqualified 4 of the rabbits. Pull-out strength levels at 10-30
      days (n = 7), 31-60 days (n = 10), 61-90 days (n=4), and all (n=21) were,
      respectively, 107.1 +/- 58.1, 111.4 +/- 42.7, 97.0 +/- 21.3, and 107.2 +/- 43.9
      for MyoCouplers and 58.4 +/- 19.4, 52.3 +/- 34.7, 40.5 +/- 13.0, and 52.1 +/-
      26.9 for the control animals. Differences were statistically significant (one
      tailed t-test for paired data) and at progressively higher standards of
      probability for each successive period (p < 0.05 at 10-30 days, p < 0.01 at 31-60
      days, p < 0.001 at 90 days, and p < 0.00001 for all). Histology showed fibrous
      tissue insinuation. Of 360 random fiber surface sites, 88% were closer to fibrous
      tissue structures than to other fibers. These findings support the aggressive
      pursuit of muscle powered mechanisms for artificial hearts, assist devices, and
      heart wall actuators.

PMID- 12790384
TI  - Synthetic human alpha-atrial natriuretic peptide infusion in management after
      open heart operations.
AB  - Cardiopulmonary bypass (CPB) induces water retention in the third space, and the
      mechanism is partially associated with the activation of the renin-angiotensin
      aldosterone system (RAAS). Atrial natriuretic peptide (ANP) has a gradual but
      strong diuretic effect and suppresses the RAAS activation. We examined the
      efficacy of synthetic human alpha-ANP (hANP) infusion in the management of the
      postoperative water balance control. Thirty patients (male:female = 18:12, 65.2
      +/- 9.5 years) undergoing elective open heart operations in 2001 were allocated
      into one of two groups. Group H (n = 14) received 0.025 microg/kg/minute of
      synthetic hANP (HANP; Suntory Inc., Zeria Pharmaceutical, Tokyo, Japan) from the
      termination of CPB; the dose was gradually reduced to 0 until the 72nd
      postoperative hour. Group C (n = 16) served as control subjects. Twenty-four
      hours after operation, the central venous pressure, mean pulmonary arterial
      pressure, and pulmonary capillary wedge pressure were significantly lower in
      group H than in group C, and the cardiac index was significantly higher in group
      H. Total volume of plasma solution infused during the initial 24 postoperative
      hours was significantly smaller in group H. The total dosages of furosemide and
      potassium-chloride added during the first 72 postoperative hours were
      significantly smaller in group H. On the first postoperative day, plasma levels
      of renin activity and aldosterone were significantly lower in group H. These
      results suggest that postoperative hANP infusion, which provides a sufficient
      diuretic effect and suppresses CPB induced RAAS activation, may simplify
      management after open heart operations.

PMID- 12790385
TI  - Advance in animal experiments with the undulation pump total artificial heart: 50
      and 54 day survival periods with 1/R control.
AB  - The undulation pump total artificial heart (UPTAH) is a unique, implantable,
      total artificial heart (TAH) that uses undulation pumps. To achieve long-term
      survival in animals with physiologic hemodynamic conditions, a control method
      based on conductance and arterial pressure was applied to UPTAH. With this
      control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6
      kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No.
      0016, 1/R control was applied to the left pump, whereas in No. 0030, it was
      applied to the right pump. Another pump was used for left-right balance control.
      The control stability was better in No. 0030 than in No. 0016. The sucking effect
      of the left atrium was remarkable in No. 0016, possibly because of a time delay
      when left-right balance control was performed with the right pump. In No. 0016,
      the cause of death was probably a thrombus flown from a panus in the left atrium.
      It is possible that the left atrial suction effect influenced the thrombus and
      panus formation in the left atrium. In No. 0030, the cause of death was a small
      rupture of the membrane in the right pump. The rupture may have been caused by
      excessive negative pressure inside the pump. This pressure resulted from suction
      of the right atrium because of an unexpected control excursion, which was
      probably caused by a software bug. It will be necessary to redesign the
      undulation pump and improve the software to achieve longer survival periods for
      animals with physiologic hemodynamic conditions.

PMID- 12790386
TI  - Newly developed ventricular assist device with linear oscillatory actuator.
AB  - The goal of this study was to develop a new direct electromagnetic left
      ventricular assist device (DEM-LVAD) with a linear oscillatory actuator (LOA).
      The DEM-LVAD is a pulsatile pump with a pusher plate. The pusher plate is driven
      directly by the mover of the LOA. The LOA provides reciprocating motion without
      using any movement converter such as a roller screw or a hydraulic system. It
      consists of a stator with a single winding excitation coil and a mover with two
      permanent magnets. The simple structure of the LOA is based on fewer parts to
      bring about high reliability and smaller size. The mover moves back and forth
      when forward and backward electric current is supplied to the excitation coil.
      The pump housings have been designed using three-dimensional computer aided
      design software and fabricated with the aid of computer aided manufacturing
      technology. Monostrut valves (Bjork-Shiley #21) were used for the prototype. The
      DEM-LVAD dimension is 96 mm in diameter and 50 mm thick with a mass of 0.62 kg
      and a volume of 280 ml. An in vitro test (afterload 100 mm Hg; preload 10 mm Hg;
      input power 10 W) demonstrated more than 6 L/minute maximum output and 15%
      maximum efficiency at 130 beats per minute (bpm). Dynamic stroke volume ranged
      between 40 and 60 ml. The feasibility of the DEM-LVAD was confirmed.

PMID- 12790387
TI  - Development of a database of patients supported by ventricular assist devices.
AB  - An increase in the number of patients with end stage heart failure is leading to
      increased use of ventricular assist devices (VAD). However, sometimes the optimal
      time point for implantation of left ventricular or biventricular support remains
      unclear. Data analysis using an electronic database may help to make the decision
      making process more precise and thus improve outcome. However, it is not easy to
      find a balance between sufficient comprehensiveness of the data, which are
      selected from a huge amount of available information, and practicability of
      database maintenance and data analysis. We developed the Assist Database based on
      Access for Windows. The Assist Database consists of five main parts: (1)
      demographic and admission data, diagnosis, goal, and type of VAD; (2)
      preoperative period; (3) postoperative period up to 30 days; (4) follow-up
      period; and (5) statistical evaluation. The preoperative and postoperative parts
      include hemodynamic data; ventilatory support; laboratory results; results from
      echocardiographic, neurologic, pathologic, and other examinations; medication;
      and complications. The follow-up part documents readmissions, complications, and
      outcome. From April 1987 to October 2002, eight different types of VAD were
      implanted in 654 patients in our institution. Their data were retrospectively
      added to the Assist Database using medical records and different previously used
      electronic databases. Since the Assist Database came into routine use, it has
      been supplied daily with selected data of current patients. On the data entry
      level, the data arising from medical records are entered either manually via
      standard forms or automatically from other electronic documentation systems used
      in our hospital in routine patient care to collect laboratory results,
      demographic data, blood transfusion data, and operative data and from electronic
      patient charts via interfaces. The structure of the database is designed to
      facilitate the data analysis level. The database presented is one of three
      databases united to form a network. The structure of the Assist Database
      facilitates comprehensive, time saving data collection, which allows different
      online data analyses. These analyses may affect the decision making process and
      thus improve outcome. However, achieving a balance between the volume of
      available information, the time consumed, and the relevance of the data for
      further analysis remains difficult. The Assist Database should include
      information relevant for the decision making process and for the prediction of
      outcome. In particular, data collection should be focused on patients'
      preoperative condition and on postoperative organ function and quality of life.
      Further, different databases (for patients with congestive heart failure, assist
      device patients, and transplanted patients) should be unified to form a network
      to avoid the repeated collection of identical data, to save time, and to increase
      the quality of analysis. In the long-term, multicenter use of the Assist Database
      could be considered.

PMID- 12790388
TI  - Physiological adaptation to a nonpulsatile biventricular assist system.
AB  - Physiological adaptation of the recipient to a nonpulsatile biventricular assist
      system (NPBVAS) is not well understood. The aim of this study is to evaluate the
      physiological adaptation of experimental animals after NPBVAS implantation. Since
      May 2001, four long-term NPBVAS implant experiments in calves were performed. The
      blood gas and hemodynamic data were analyzed retrospectively. An additional
      prospective experiment was performed to confirm retrospective findings. All
      calves (n = 5) lived longer than 5 weeks without complication. In retrospective
      analysis, there was not a correlation between the O2 content and total blood flow
      in the pulmonary artery during the 1st postoperative week, but they began to
      correlate within the 2nd postoperative week. Then, there was a strong correlation
      after the 3rd postoperative week (r = 0.753). In the prospective experiment, O2
      content related to total pulmonary flow after 2 weeks (r = 0.732) was the same as
      in the retrospective study. Most of the hemodynamic parameters studied became
      normalized after 14 days. In addition, easier controllability of the blood pumps
      was demonstrated after the 2nd postoperative week in all five experiments.
      Experimental results suggested that the native healthy heart accepted NPBVAS by
      reducing its cardiac output in 2 weeks. In addition, complicated control of the
      BPVAS was not necessary after 2 weeks of implantation. These results demonstrate
      the possibility of physiological adaptation to the NPBVAS being established
      within 2 postoperative weeks.

PMID- 12790389
TI  - Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian
      elephants (Elephas maximus).
AB  - The deaths of two Asian elephants (Elephas maximus) in August 1996 led the United
      States Department of Agriculture to require the testing and treatment of
      elephants for tuberculosis. From August 1996 to September 1999. Mycobacterium
      tuberculosis infection was confirmed by culture in 12 of 118 elephants in six
      herds. Eight diagnoses were made antemortem on the basis of isolation of M.
      tuberculosis by culture of trunk wash samples; the remainder (including the
      initial two) were diagnosed postmortem. We present the case histories,
      epidemiologic characteristics, diagnostic test results, and therapeutic plans
      from these six herds. The intradermal tuberculin test, enzyme-linked
      immunosorbent assay serology, the blood tuberculosis test, and nucleic acid
      amplification and culture are compared as methods to diagnose M. tuberculosis
      infection in elephants.

PMID- 12790390
TI  - Humoral immune responses of black-footed penguins (Spheniscus demersus) after DNA
      mediated immunization with a beta-galactosidase reporter gene.
AB  - Humoral immune responses of black-footed penguins (Spheniscus demersus) to DNA
      mediated immunization with a beta-galactosidase reporter gene expression plasmid
      were evaluated. Six male and 6 female adult penguins received either test
      plasmid, pCMV-beta, containing the beta-galactosidase gene or control plasmid,
      pCI, lacking a gene for expression. Three birds from each group were used
      previously in a diluent control group and given one injection of sterile saline.
      All samples were screened for anti-beta-galactosidase antibodies by indirect
      enzyme-linked immunosorbent assay with anti-chicken immunoglobulin G as secondary
      antibody. Antibodies to beta-galactosidase were detected in the sera of pCMV-beta
      inoculated penguins, with a peak response on day 21. Antibody titers of the test
      plasmid group versus both control groups on days 21, 28, and 42 differed
      significantly. These results demonstrate that black-footed penguins can be safely
      transfected with the gene encoding beta-galactosidase and will mount a humoral
      response against the in vivo-expressed protein. Knowledge from this initial study
      can be applied to the development of DNA-mediated vaccines against specific
      infectious diseases of penguins.

PMID- 12790391
TI  - Detection of feline coronavirus infection in captive cheetahs (Acinonyx jubatus)
      by polymerase chain reaction.
AB  - Feline coronavirus genetic elements were detected by polymerase chain reaction
      from blood, fecal samples, and effusive fluid collected from 33 cheetahs in the
      U.S.A. Feline coronavirus-specific serum antibodies were also measured by
      indirect immunofluorescence. Ten cheetahs were positive for viral shedding by
      polymerase chain reaction, whereas 13 were seropositive by immunofluorescence.
      Results of serology did not consistently correlate with shedding of virus, and
      the capture antigen used for detection of feline coronavirus-specific antibodies
      had a significant impact on results. Testing of samples from one population over
      a 1-yr period indicated chronic infection in some animals. These relatively
      healthy carrier animals were a source of virus for contact animals. Screening
      programs in cheetah populations for feline coronavirus infection may be most
      reliable if a combination of serologic analysis and viral detection by polymerase
      chain reaction is used.

PMID- 12790392
TI  - Clinical implications of rhinoceros reproductive tract anatomy and histology.
AB  - Reproductive tracts or tissues from five male black rhinoceroses (Diceros
      bicornis), two male white rhinoceroses (Ceratotherium simum), two male one-horned
      Asian rhinoceroses (Rhinoceros unicornis), seven female black rhinoceroses, and
      six female white rhinoceroses from multiple institutions were examined to
      characterize their anatomy and histology. Some observations and measurements were
      obtained from in situ tracts of intact animals before or during necropsy.
      Formalin-fixed tissues were dissected and examined histologically. Retrospective
      reproductive data from each rhinoceros was obtained from the institutions of
      origin. Reproductive histology of these species was similar to that of other
      mammals. Male accessory gland structure varied among species, and the Asian
      rhinoceros epididymis was more loosely attached and had larger duct diameters
      than did the epididymides of the African species. Although histology was
      typically mammalian, rhinoceros reproductive morphology combined characteristics
      of several different mammals. Defining this unique morphology of rhinoceroses may
      help in understanding their reproductive physiology and will effect the
      development of appropriate reproductive techniques.

PMID- 12790393
TI  - Electrocardiography, heart rates, and heart weights of free-living birds.
AB  - To examine the waveforms of electrocardiograms, cardiac rhythm, heart rates at
      rest and during excitement, and the rate of increase of heart rate,
      electrocardiograms were recorded with standard bipolar limb leads from 79 free
      living birds, including 19 species. The heart weights and heart-to-body weight
      ratios were obtained from an additional 96 free-living birds, including 20
      species. In the majority of the electrocardiograms, lead I was of low amplitudes
      for all waves except the P wave, and leads II and II were very similar to each
      other with a predominant S wave and a very short or elevated ST segment. The P
      wave was often superimposed on the T wave when the heart rate increased to 330
      beats/min. Four types of arrhythmia were observed in 50 of the 79 birds (63.3%):
      48 sinus arrhythmias, four sinus arrests, two atrial premature contractions, and
      one ventricular premature contraction. The resting heart rate was negatively
      associated with the rate of increase, suggesting that a bird with a low resting
      rate might be able to maintain a greater capacity to increase its heart rate than
      one with a high resting rate. A negative correlation on a bilogarithmic scale was
      obtained between the heart weight and the resting heart rate, indicating that a
      bird with a high heart weight had lower resting heart rate than a bird with a low
      heart weight. When the heart-to-body weight ratios of free-living birds were
      compared according to their motility, the ratios of more active birds were
      greater than those of less active ones.

PMID- 12790394
TI  - Inactivated suckling mouse brain rabies vaccine provides short-term immunity in
      capuchin monkeys (Cebus apella).
AB  - Eight capuchin monkeys (Cebus apella) were vaccinated against rabies with an
      inactivated suckling mouse brain vaccine (SMBV). Three 1-ml doses of 2% brain
      tissue suspension were given by i.m. injection at 0, 30, and 60 days. Blood
      samples were collected at 0, 30, 60, 90, 150, 210, 240, 300, and 365 days and
      were tested by simplified fluorescence inhibition to titer-neutralizing
      antibodies. All of the animals developed neutralizing antibodies with titers >0.5
      IU/ml after vaccination, but the immune response persisted for only 122.3 +/-
      32.6 days. The SMBV was able to induce immune response in the capuchin monkeys,
      but protection was short-lived.

PMID- 12790395
TI  - Inflammatory arthritis in canids: spondyloarthropathy.
AB  - Spondyloarthropathy was observed in 25 (2.8%) of 895 preserved canid museum
      specimens and was catalogued by species. The associated skeletal alterations in
      canids are indistinguishable grossly and physiologically from those in humans
      with spondyloarthropathy of the reactive type. Rate of affliction was independent
      of captive or wild-caught status or gender. In canids, spondyloarthropathy was
      much more common than osteoarthritis (0.3%), which predominantly is limited to
      captive animals. Animal well-being may be enhanced by recognition of the
      condition and initiation of specific treatment.

PMID- 12790396
TI  - Use of monoclonal antibodies developed against chicken coccidia (Eimeria) to
      study invasion and development of Eimeria reichenowi in Florida sandhill cranes
      (Grus canadensis).
AB  - Eimeria gruis and Eimeria reichenowi are common coccidial parasites of a number
      of species of cranes. Until recently, little was known about either the site for
      invasion or the dynamics of early development of the crane coccidia because of
      the difficulty of identifying sporozoites and early developmental stages of these
      parasites by conventional staining methods. In the present study, monoclonal
      antibodies (MAbs) elicited against Eimeria spp. of chickens and turkeys were
      found to cross-react with sporozoites and developmental stages of E. reichenowi
      in the tissues of Florida sandhill cranes (Grus canadensis). With these Mabs, E.
      reichenowi sporozoites were found in specimens taken at 6 hr postinoculation (PI)
      from just proximal to Meckel's diverticulum in the jejunum to the ileocecal
      juncture. Fewer were found in the ceca and rectum and none in the duodenal loop.
      At 24 hr PI, there were markedly fewer sporozoites and their location had shifted
      to the duodenum. No stages were seen in intestinal cells at 5 days PI (DPI), but
      trophozoites had developed in the liver and spleen. At 10 DPI, sexual stages were
      detected in the intestine from the duodenal loop through Meckel's diverticulum
      but not in other organs. By 14 DPI, numerous developmental stages were detected
      in the intestine (ceca and jejunum), liver, and lungs but not in the heart,
      kidney, or brain. The number, location, and maturity of the stages in the ceca
      differed markedly from those in the jejunum.

PMID- 12790397
TI  - Intestinal and blood parasites in Amazon parrots destined for relocation in
      Guatemala.
AB  - Approximately 350 Amazon parrots were destined for relocation in Peten province,
      northeastern Guatemala. In random sampling of the parrots, 95 blood and 75 fecal
      samples were examined individually for parasites. Coccidia were present in 6.0%
      (3/50) of Amazona autumnalis autumnalis, and they were the only parasites
      detected. There were no blood parasites observed in 64 A. a. autumnalis, four
      Amazona pionus senilis, 16 Amazona ferinosa guatemala, 10 Amazona albifronsus
      albifronsus, and one Amazona xantholora. No fecal parasites were observed in four
      A. p. senilis, 12 A. f. guatemala, eight A. a. albifronsus, and one A.
      xantholora.

PMID- 12790398
TI  - Intravenous pharmacokinetics of penicillin G and antipyrine in ostriches
      (Struthio camelus) and emus (Dromaius novaehollandiae).
AB  - Penicillin G and antipyrine, which served as model drugs to assess the relative
      capacities of renal and hepatic elimination pathways, respectively, were each
      administered intravenously to six ostriches (Struthio camelus) and to six emus
      (Dromaius novaehollandiae). Drug concentrations in blood samples collected over a
      period of 12 hr after administration were assayed, and elimination half-life,
      mean residence time, clearance, and steady-state volume of distribution were
      calculated. Mean values for elimination half-life and mean residence time of
      penicillin G were significantly higher in emus than in ostriches; no significant
      differences in antipyrine pharmacokinetics between species were demonstrated.

PMID- 12790399
TI  - Serologic response of maned wolves (Chrysocyon brachyurus) to canine and canine
      parvovirus vaccination distemper virus.
AB  - This study evaluated the immune response of 47 (22 males, 25 females) captive
      maned wolves (Chrysocyon brachyurus) to modified-live canine parvovirus and
      canine distemper virus (Onderstepoort and Rockborn strains) vaccines. Sera were
      collected from 33 adults and 14 pups, including five free-ranging pups captured
      at 1 yr of age or younger. All the adults and four captive-born pups had been
      vaccinated prior to this first blood collection. Virus neutralization and
      hemagglutination-inhibition assays were performed for quantitating antibodies
      against canine distemper and canine parvovirus, respectively. Distemper antibody
      titers > or = 100 were present in 57% of adults and 14% of pups. All adults and
      29% of pups had parvovirus antibody titers > or = 80. After vaccination, 72% of
      the wolves developed antibody titers > or = 100 against distemper and 98%
      developed titers > or = 80 against parvovirus. Both vaccines used were safe and
      immunogenic to juvenile and adult maned wolves, regardless of prior vaccination
      history.

PMID- 12790400
TI  - Use of naloxone to reverse carfentanil citrate-induced hypoxemia and
      cardiopulmonary depression in Rocky Mountain wapiti (Cervus elaphus nelsoni).
AB  - With the use of a crossover study design, we investigated the respiratory and
      cardiovascular effects of naloxone administration in eight healthy Rocky Mountain
      wapiti (Cervus elaphus nelsoni) anesthetized with carfentanil (10 microg/kg i.m.)
      and xylazine (0.1 mg/kg). Anesthetized animals showed profound hypoxemia with
      mild hypercapnia, tachycardia, hypertension, and acidosis prior to naloxone
      administration. After monitoring equipment was placed, animals were administered
      either naloxone (2 microg/microg carfentanil i.v.) or an equivalent volume of
      normal saline. Mean values for PaO2, PaCO2, heart rate, and respiratory rate were
      significantly different between naloxone- and saline-treated groups, but mean
      blood pressure, hematocrit, and serum electrolyte concentrations were not. Mean
      PaO2 was 23.0 +/- 4.1 mm Hg prior to administration of naloxone or saline and
      increased to 50.2 +/- 7.3 mm Hg after naloxone administration. Mean PaO2 of
      saline-treated animals did not change significantly. Electrocardiograms of three
      saline-treated animals suggested myocardial hypoxia. Hypoxemia appeared to be
      caused by respiratory depression, hemodynamic alterations, and lateral
      recumbency. All but one animal remained anesthetized after naloxone
      administration. Anesthesia in all animals was reversed in < or = 4 min with
      naltrexone (100 mg/mg carfentanil i.v. s.c.) and yohimbine (0.1 mg/kg i.v.). One
      bolus of naloxone improved oxygenation in carfentanil-xylazine-anesthetized
      wapiti.

PMID- 12790402
TI  - Mycobacterium avium infection in an ostrich (Struthio camelus).
AB  - Acid-fast organisms were identified by histopathology of granulomatous lesions in
      an ostrich (Struthio camelus). The organisms were grown in Herrold's egg media
      with and without mycobactin and identified as Mycobacterium avium. An agar gel
      immunodiffusion (AGID) test for Mycobacterium avium paratuberculosis was
      performed for detection of antibody for M. avium in this infected ostrich and
      seven other ostriches that were in contact. The results of the AGID were
      consistent with the pathologic diagnosis of mycobacteriosis and the isolation of
      M. avium in the affected ostrich.

PMID- 12790401
TI  - Myelogenous leukemia in a bearded dragon (Acanthodraco vitticeps).
AB  - A 3-yr-old bearded dragon (Acanthodraco vitticeps) presented with lethargy, a
      swollen right elbow joint, inability to move its rear limbs normally, and marked
      leukocytosis. The majority of leukocytes were an abnormal mononuclear lymphoid
      type cell with a high nuclear to cytoplasmic ratio, a slightly blue cytoplasm,
      nuclei with coarsely granular chromatin, and some nuclear clefts. Acute leukemia
      of lymphoid or myeloid origin was tentatively diagnosed. The abnormal mononuclear
      leukocyte cell population stained positively for the myeloid cytochemical stains:
      peroxidase, chloroacetate esterase, and L1-calprotectin. The abnormal cell
      population of the peripheral blood did not stain with the lymphoid cytochemical
      stains: alpha-naphthyl butyrate esterase, CD3, and CD79a.

PMID- 12790403
TI  - Cryptosporidium sp.-associated enteritis without gastritis in rough green snakes
      (Opheodrys aestivus) and a common garter snake (Thamnophis sirtalis).
AB  - An epizootic of severe Cryptosporidium sp.-associated enteritis occurred in a
      group of 15 wild-caught juvenile rough green snakes (Opheodrys aestivus) at the
      Baltimore Zoo quarantine facility. All of the animals died with no premonitory
      signs. Histopathologic examination of the small and proximal large intestine of
      eight of the green snakes showed moderate to severe Cryptosporidium sp. infection
      and enteritis characterized by dense heterophilic and lymphocytic inflammatory
      infiltrates throughout the lamina propria with epithelial necrosis.
      Cryptosporidium sp. was also found in feces of an adult common garter snake
      (Thamnophis sirtalis) that was wild caught on zoo grounds and held in quarantine
      during the epizootic. After euthanasia, histologic examination of the garter
      snake showed a severe small intestinal Cryptosporidium sp. infection with only
      mild enteritis consisting of sparse heterophilic and lymphocytic infiltrates.
      There was no gross or histologic evidence of Cryptosporidium sp. gastritis in the
      nine snakes evaluated, and this is the first report of Cryptosporidium sp.
      associated enteritis in snakes without gastric lesions.

PMID- 12790404
TI  - Strongyloidiasis in a Cope's grey tree frog (Hyla chrysoscelis).
AB  - A male Cope's grey tree frog (Hyla chrysoscelis) died spontaneously with ventral
      subcutaneous edema and was necropsied. Thickening of the intestinal mucosa was
      observed histopathologically, with villous atrophy and intraepithelial nematodes
      present. Adult female Strongyloides sp. nematodes were isolated from the fixed
      intestinal tract, the first time this nematode genus has been recovered from this
      frog genus. Intestinal strongyloidiasis should be considered as a cause for
      protein-losing enteropathy and death in frogs.

PMID- 12790405
TI  - Preductal aortic coarctation and patent ductus arteriosus in a Sumatran tiger
      (Panthera tigris sumatrae) cub.
AB  - Preductal aortic coarctation and patent ductus arteriosus are described in a
      neonatal Sumatran tiger, Panthera tigris sumatrae. Eight days postpartum, the cub
      appeared weak, and it was separated from the dam for hand rearing. On examination
      it was dehydrated and hypothermic. Despite treatment, the animal's condition
      worsened and the cub died 12 days postpartum. Gross postmortem and histologic
      examinations revealed a preductal aortic coarctation and patent ductus arteriosus
      with a patent foramen ovale and moderate dilatation of the right ventricle of the
      heart. Focal pneumonia and mild hepatitis were also present; however, diffuse
      pulmonary congestion and edema were considered to be the proximate cause of
      death.

PMID- 12790406
TI  - Ivermectin toxicosis in a chameleon (Chamaeleo senegalensis) infected with
      Foleyella furcata.
AB  - Both male and female Foleyella furcata were found in the subcutaneous tissue and
      abdominal cavity of an adult male wild-caught Senegalese chameleon (Chamaeleo
      senegalensis). This nematode species is endemic to Madagascar but has never been
      recorded from the continent of Africa. Prior to the chameleon's death, a
      migrating worm was seen under the skin in the abdominal and thoracic region. Huge
      numbers of small, sheathed microfilariae were detected in the blood smears. The
      chameleon was treated with a single dose (0.2 mg/kg s.c.) of ivermectin. Serious
      adverse reactions (complete inertia) developed within 24 hr after injection and
      lasted for 7 days, indicating either ivermectin toxicity or a systemic reaction
      involving the release of endotoxins from the microfilariae dying in the
      bloodstream as a result of parasiticide therapy. Therefore, ivermectin treatment
      of chameleons infected with Foleyella should be avoided.

PMID- 12790407
TI  - Diagnosis and management of a patent urachus in a white rhinoceros calf
      (Ceratotherium simum simum).
AB  - A 10-day-old female southern white rhinoceros calf (Ceratotherium simum simum)
      was diagnosed with a patent urachus after urine was observed dribbling from the
      umbilicus. After being separated from its mother, the animal was sedated with
      i.m. butorphanol and anesthetized with isoflurane in oxygen for surgical
      correction of the patent urachus. Mild postoperative complications involved
      seroma formation and partial skin incision dehiscence, which necessitated three
      follow-up immobilizations for reevaluation and treatment of the surgical site.
      Histopathology did not reveal an infectious etiology as the cause for the
      complications or for the patent urachus. The etiology of the patent urachus in
      this animal remains undetermined. This report represents the first documented
      case of a patent urachus in a white rhinoceros.

PMID- 12790408
TI  - Exposure of hooded capuchin monkeys (Cebus apella cay) to a rabid bat at a
      zoological park.
AB  - On 27 May 1999, a big brown bat (Eptesicus fuscus) was discovered on an island
      exhibit at the Denver Zoo that contained a troop of 15 hooded capuchin monkeys
      (Cebus apella cay). The monkeys were attacking the bat when it was discovered.
      The bat was collected and humanely euthanatized without direct handling and
      submitted to the Colorado Department of Public Health and Environment Virology
      Laboratory for rabies evaluation. The monkeys had not been vaccinated against
      rabies virus. The next day, the laboratory confirmed that the bat was positive
      for rabies. The recommendations from the Colorado Department of Public Health and
      Environment and the Centers for Disease Control and Prevention were to
      euthanatize the monkeys or quarantine them and comply with the human
      nonvaccinated postexposure protocol. A 1-ml dose of a killed rabies vaccine was
      administered i.m. in the hip on each of days 2, 7, 12, 19, and 33 postexposure,
      and a single dose of human rabies immune globulin was administered i.m. 5 days
      postexposure. Blood was collected under anesthesia in order to evaluate the
      immune response after rabies vaccination from six monkeys 5 days postexposure,
      six monkeys 19 days postexposure (five of the six monkeys were the same monkeys
      bled 5 days postexposure), 15 monkeys 67 days postexposure, and 13 monkeys
      approximately 1 yr postexposure. All of the monkeys developed and maintained
      levels of rabies virus neutralizing antibody above 0.05 IU/ml by 67 days
      postexposure. Although a serologic titer of 0.05 IU/ml indicates an adequate
      human response after rabies vaccination, no similar information is available for
      nonhuman primates. To date, none of the monkeys has succumbed to rabies.

PMID- 12790409
TI  - Antibody response to rabies vaccination in captive and free-ranging wolves (Canis
      lupus).
AB  - Fourteen captive and five free-ranging Minnesota gray wolves (Canis lupus) were
      tested for the presence of rabies virus neutralizing antibodies (RVNA) after
      vaccination with an inactivated canine rabies vaccine. Blood was collected from
      all wolves prior to vaccination and at 1 mo postvaccination (PV) and from all
      captive and three wild wolves at 3 mo PV. In addition, one free-ranging wolf was
      sampled at 4 mo PV, and two free-ranging wolves were sampled at 6 mo PV. All
      wolves were seronegative prior to vaccination. RVNA were detected in 14 (100%)
      captive wolves and in four of five (80%) free-ranging wolves. The geometric mean
      titer of the captive wolves at 1 mo PV was significantly higher (P = 0.023) than
      in the free-ranging wolves. Five of 13 (38.5%) captive wolves and none of the
      three (0%) free-ranging wolves had measurable RVNA at 3 mo PV. No measurable RVNA
      were detected in the serum samples collected from the free-ranging wolves at 4
      and 6 mo PV. These results should be interpreted with caution because of the
      small number of free-ranging wolves tested. Further research is needed to
      properly assess immune function and antibody response to vaccination in captive
      wolves in comparison with their free-ranging counterparts.

PMID- 12790410
TI  - Cytogenetic identification of a hybrid owl monkey, Aotus nancymaae x Aotus
      lemurinus griseimembra.
AB  - A neonate male owl monkey (Aotus sp.) was identified cytogenetically as a hybrid
      after it failed to nurse and died. Phenotypically, the male parent possessed
      characteristics of the "gray-neck group," and G-banded karyotypes identified him
      as Aotus lemurinus griseimembra (2n = 53), heterozygous for the centric fusion of
      chromosomes 13 and 14. The female parent belonged to the "red-neck group" and was
      identified cytogenetically as Aotus nancymaae (2n = 54). The neonate hybrid had
      2n = 54 chromosomes with 13 homologous pairs of autosomes, 26 nonhomologous
      autosomes, and XY sex chromosomes. Thirteen of the nonhomologous chromosomes
      represented the paternal complement, and 13 were from the maternal complement.
      Chromosomal rearrangements occurring between the karyotypes of A. l. griseimembra
      and A. nancymaae were believed to include two paracentric inversions, a
      reciprocal translocation, and two complex rearrangements involving pericentric
      inversion, telocentromeric fusion, and centromeric adjustment. Cytogenetic
      analyses are necessary to identify most Aotus taxa and thus should be utilized to
      pair chromosomally compatible animals and avoid interspecies hybridization.

PMID- 12790411
TI  - Clostridium perfringens enterotoxicosis in two Amur leopards (Panthera pardus
      orientalis).
AB  - Two 6-yr-old male sibling Amur leopards (Panthera pardus orientalis) housed
      together at the Pittsburgh Zoo presented for acute onset of diarrhea with no
      changes in appetite or behavior. Heat-fixed modified Wright-stained and Gram
      stained fecal smears revealed a mixed bacterial population with a large number of
      gram-positive Clostridium perfringens-like spores (>20 per high-power oil
      immersion field). In addition, C. perfringens enterotoxin was isolated from one
      leopard at 1:256, confirming the presence of C. perfringens enterotoxicosis.
      Treatment with oral metronidazole, tylosin tartrate, and psyllium fiber was
      prescribed, with return of more normal stool by the third day of treatment. Fecal
      consistency steadily improved and was considered normal by the time all
      prescribed treatments were complete. Diarrhea has not recurred. Partially thawed
      meat in the leopards' diet may have precipitated the production of an endogenous
      clostridial enterotoxicosis by disrupting digestive tract flora with resultant
      clostridial overgrowth and sporulation.

PMID- 12790412
TI  - Exposure of game birds to ochratoxin A through supplemental feeds.
AB  - Thirty randomly selected game bird feeders were sampled at 25-33-day intervals
      from November 1996 to March 1997 to quantitate ochratoxin A concentrations in
      supplemental feed. Monthly mean ochratoxin A concentration of grain in feeders
      was 8.3 +/- 0.8 ppb (n = 167). Ochratoxin A concentrations from individual
      feeders ranged from <5 to 109.9 ppb, levels that have not been demonstrated to
      negatively affect game birds in a laboratory environment. Stress may increase the
      chance of ochratoxin-induced mortality or morbidity for wild game birds. Only
      mean relative humidity was significantly correlated with monthly mean ochratoxin
      A concentration.

PMID- 12790413
TI  - Clinical challenge. Pectus excavatum and gastrointestinal gaseous dilatation with
      secondary compression of the thoracic cavity.

PMID- 12790414
TI  - Clinical challenge. Hydrocephalus.

PMID- 12790415
TI  - The veterinarian's role in biodiversity conservation.

PMID- 12790416
TI  - Cardiopulmonary assessment of medetomidine, ketamine, and butorphanol anesthesia
      in captive Thomson's gazelles (Gazella thomsoni).
AB  - This investigation evaluated the cardiopulmonary effects of medetomidine,
      ketamine, and butorphanol anesthesia in captive juvenile Thomson's gazelles
      (Gazella thomsoni). Butorphanol was incorporated to reduce the dose of
      medetomidine necessary for immobilization and minimize medetomidine-induced
      adverse cardiovascular side effects. Medetomidine 40.1 +/- 3.6 microg/kg,
      ketamine 4.9 +/- 0.6 mg/kg, and butorphanol 0.40 +/- 0.04 mg/kg were administered
      intramuscularly by hand injection to nine gazelles. Times to initial effect and
      recumbency were within 8 min postinjection. Cardiopulmonary status was monitored
      every 5 min by measuring heart rate, respiratory rate, indirect blood pressure,
      end-tidal CO2, and indirect oxygen-hemoglobin saturation by pulse oximetry.
      Venous blood gases were collected every 15 min postinjection. Oxygen saturations
      less than 90% in three gazelles suggested hypoxemia. Subsequent immobilized
      gazelles were supplemented with intranasal oxygen throughout the anesthetic
      period. Sustained bradycardia (<60 beats per minute, as compared with
      anesthetized domestic calves, sheep, and goats) was noted in eight of nine
      gazelles. Heart and respiratory rates and rectal temperatures decreased slightly,
      whereas systolic, mean, and diastolic blood pressure values were consistent over
      the anesthetic period. Mild elevations in end tidal CO2 and PCO2 suggested
      hypoventilation. Local lidocaine blocks were necessary to perform castrations in
      all seven of the gazelles undergoing the procedure. Return to sternal recumbency
      occurred within 7 min and return to standing occurred within 12 min after
      reversal with atipamezole (0.2 +/- 0.03 mg/kg) and naloxone (0.02 +/- 0.001
      mg/kg). Medetomidine, ketamine, and butorphanol can be used to safely anesthetize
      Thomson's gazelles for routine, noninvasive procedures. More invasive procedures,
      such as castration, can be readily performed with the additional use of local
      anesthetics.

PMID- 12790417
TI  - A modified protocol for sex identification of in ovo avian embryos and its
      application as a management tool for endangered species conservation programs.
AB  - A simple, reliable, and safe protocol was developed for the collection of small
      amounts of blood from avian eggs of variable size and at early stages of
      development. Fifty eggs were used in the study; 40 were common chicken (Gallus
      domesticus) eggs, six were homing pigeon (Columba livia domestica) eggs, and four
      were burrowing owl (Athene cunicularia) eggs. Collection was attempted
      approximately halfway through incubation. The success rate for collection of
      blood or blood-tinged fluid from eggs was high, averaging 68% in the chicken
      eggs, 100% in the homing pigeon eggs, and 75% in the burrowing owl eggs.
      Collection did not affect subsequent hatchability. This blood could then be used
      to determine the sex of the embryo by utilizing a DNA probe or restriction
      fragment length polymorphism technique. Sex identification in ovo allowed the
      demographic management of small populations of birds within our institution.

PMID- 12790418
TI  - Chemical anesthesia of northern sea otters (Enhydra lutris): results of past
      field studies.
AB  - Between 1987 and 1997, we chemically immobilized 597 wild sea otters (Enhydra
      lutris) in Alaska for the collection of biological samples or for surgical
      instrumentation. One drug-related sea otter fatality occurred during this time.
      Fentanyl in combination with diazepam produced consistent, smooth inductions with
      minimal need for supplemental anesthetics during procedures lasting 30-40 min.
      Antagonism with naltrexone or naloxone was rapid and complete, although we
      observed narcotic recycling in sea otters treated with naloxone. For surgical
      procedures, we recommend a fentanyl target dose of 0.33 mg/kg of body mass and
      diazepam at 0.11 mg/kg. For nonsurgical biological sample collection procedures,
      we recommend fentanyl at 0.22 mg/kg and diazepam at 0.07 mg/kg. We advise the use
      of the opioid antagonist naltrexone at a ratio of 2:1 to the total fentanyl
      administered during processing.

PMID- 12790419
TI  - Development of a standardized nomenclature for bronchoscopy of the respiratory
      system of harbor porpoises (Phocoena phocoena).
AB  - Respiratory disease is common in captive and wild cetaceans. Bronchoscopy may
      permit early diagnosis of respiratory disease in dolphins and porpoises.
      Refinement of cetacean bronchoscopy requires development of a nomenclature system
      to facilitate description of the anatomic site at which lesions occur. A standard
      bronchoscopic nomenclature also permits serial evaluations of lesions and
      enhances communication between veterinarians. In this project, we adapted the
      bronchoscopic nomenclature devised by Amis and McKiernan for the dog and horse to
      the harbor porpoise (Phocoena phocoena). Silastic and air-dried models of the
      bronchial tree of the harbor porpoise were made to illustrate the anatomy and
      devise the nomenclature. Bronchial anatomy was consistent among the four porpoise
      lungs studied. The Amis and McKiernan nomenclature was readily adaptable to the
      harbor porpoise lung with minor modifications and may be useful for cetacean
      bronchoscopy.

PMID- 12790420
TI  - Experimental inoculation of broad-nosed caimans (Caiman latirostris) and Siamese
      crocodiles (Crocodylus siamensis) with Mycoplasma alligatoris.
AB  - An outbreak of mycoplasmosis caused by Mycoplasma alligatoris resulted in the
      death or euthanasia of 60 American alligators (Alligator mississippiensis) from a
      population of 74 captive bull alligators in Florida in 1995. The natural
      reservoir, routes of transmission, and host range of M. alligatoris are unknown.
      This study was undertaken to determine whether crocodilian species other than
      American alligators are susceptible to M. alligatoris. Six broad-nosed caimans
      (Caiman latirostris) and six Siamese crocodiles (Crocodylus siamensis) were
      experimentally inoculated with 10(6) colony forming units (CFU) of M. alligatoris
      instilled through the glottis. Two caimans and two crocodiles were used as
      negative controls. Six and four American alligators were used as positive and
      negative controls, respectively. Three of six (50%) inoculated caimans died
      within 10 wk postinoculation (PI) of severe mycoplasmosis. Gross necropsy,
      histopathologic, and culture results were similar for broad-nosed caimans and
      American alligators. None of the inoculated Siamese crocodiles developed
      mycoplasmosis, though M. alligatoris was isolated from the tonsils in three of
      six (50%) animals at necropsy. All the inoculated crocodilians that survived
      showed significant seroconversion by 6-8-wk PI (P < 0.05). The infective dose 50%
      (ID50) and lethal dose 50% (LD50) of M. alligatoris for the broad-nosed caiman
      are 10(6) CFU when instilled through the glottis, which is similar to that of the
      American alligator. Although the host range of M. alligatoris is not restricted
      to the American alligator, the organism does not appear to be pathogenic for
      Siamese crocodiles. Other species of crocodilians may be susceptible to infection
      with M. alligatoris, and this organism should be considered when the rapid onset
      of clinical signs of pneumonia, polyarthritis, pericarditis, and death occur.

PMID- 12790421
TI  - Surgical technique for intra-abdominal radiotransmitter placement in North
      American river otters (Lontra canadensis).
AB  - Twenty-two free-ranging North American river otters (Lontra canadensis) from
      northern and eastern New York were captured and surgically implanted with
      radiotransmitters as part of a relocation project. The surgical technique
      involved an incision in the paralumbar fossa and transection through the
      abdominal musculature to introduce a radiotransmitter into the abdominal cavity.
      Two complications were encountered. Excessive hemorrhage occurred during one
      procedure. The otter was treated for blood loss with fluids, and it recovered
      uneventfully. Surgical incision infection occurred in a second animal. The otter
      was treated with metronidazole and enrofloxacin, and the wound was cleaned daily
      with chlorhexidine. The otter recovered uneventfully. Otters were released in
      western New York state. Postrelease monitoring via radiotelemetry revealed that
      the otters became established in their new ranges. The intra-abdominal implants
      did not affect their survival or reproductive potential.

PMID- 12790422
TI  - The effect of time at which plasma separation occurs on biochemical values in
      small island flying foxes (Pteropus hypomelanus).
AB  - Heparinized blood samples from 15 adult small island flying foxes (Pteropus
      hypomelanus) were stored at 22 degrees C for 0-, 6-, and 24-hr intervals prior to
      centrifugation and separation of plasma from erythrocytes. Mean plasma
      biochemical values of 16 analytes were determined from all samples. Mean values
      of blood urea nitrogen, creatinine, total protein, albumin, globulin, alkaline
      phosphatase, alanine transaminase, aspartate transaminase, cholesterol, calcium,
      sodium, and bilirubin did not change significantly over 24 hr at 22 degrees C.
      Glucose was decreased at 6 and 24 hr. Potassium and phosphorus increased and
      chloride decreased, respectively, between 6 and 24 hr.

PMID- 12790423
TI  - The prevalence and transmission to exotic equids (Equus quagga antiquorum, Equus
      przewalskii, Equus africanus) of intestinal nematodes in contaminated pasture in
      two wild animal parks.
AB  - Wild equids maintained in large enclosures may suffer from helminth diseases
      because common hygiene practices have only limited effects on parasite
      populations. Weekly monitoring of helminth prevalences and pasture infestation
      was performed for 1 yr in several extensive maintenance systems of two wildlife
      parks with similar climates to determine when veterinary intervention to control
      parasites would be useful. We also sought evidence of natural immunogenic
      reactions among herds of Chapman zebras (Equus quagga antiquorum), Przewalski's
      horses (Equus przewalskii) and dwarf donkeys (Equus asinus africanus). Fecal and
      vegetation samples and cultures for third-stage larvae revealed permanent egg
      shedding in the three species and pasture infestation during the warm, moist
      periods (July-September) in all enclosures. Stable social structure and low equid
      population density may be sufficient to make prophylaxis unnecessary in adults,
      whereas biotic and abiotic environmental factors such as crowding, animal
      transfers, social integration of subadults, and weaning stress may facilitate
      temporary severe infections of individuals. Biweekly helminth monitoring is a
      useful diagnostic tool for extensive management of exotic equids.

PMID- 12790424
TI  - Carfentanil citrate used as an oral anesthetic agent for brown bears (Ursus
      arctos).
AB  - Carfentanil citrate was given orally to five adult brown bears (Ursus arctos) on
      14 separate occasions during the winter and summer to determine effective
      anesthetic dosages and how season may alter these dosages. Lower blood urea
      nitrogen:creatinine ratios, depressed appetite, and decreased activity levels in
      the winter versus summer were reflective of different metabolic states, even
      though bears were not hibernating in the winter. Doses of carfentanil citrate
      between 6.0 and 15.2 microg/kg were mixed with 5-10 ml of honey, which the bears
      licked voluntarily from a spoon. During each anesthetization, respiratory and
      heart rates, hemoglobin saturation, temperature, electrocardiogram, blood gas
      values, and level of consciousness were monitored and utilized to determine
      effective dosages. Mean (+/- SE) dose requirements in the winter were 7.6 +/- 0.4
      microg/kg, whereas a greater mean dose of 12.7 +/- 0.5 microg/kg was required in
      the summer (P < 0.05). After ingestion began, sternal recumbency occurred in an
      average of 7.5 min (range: 4-11 min), and full restraint and safe handling was
      achieved in 21 min (range: 8-40 min). At the end of each procedure, naltrexone
      was given as the reversal agent at a ratio of 100 mg naltrexone per 1 mg
      carfentanil, with 25% of the dose given i.v. or i.m. and 75% given s.c. Mean
      reversal time was 6 min after injection of naltrexone (range: 4-9 min). Rapid
      induction and recovery times and ease of oral administration make carfentanil
      citrate an effective anesthetic agent for use in brown bears. However,
      hypoventilation and respiratory acidosis were noted in all bears, and oxygen
      insufflation is recommended.

PMID- 12790426
TI  - The timing of the onset of puberty, extension of the breeding season, and length
      of postpartum anestrus in the female mouflon (Ovis gmelini musimon).
AB  - The timing of the onset of puberty, duration of seasonal ovulatory activity, and
      length of postpartum anestrus were studied by means of blood plasma progesterone
      concentrations in a flock of European female mouflons (Ovis gmelini musimon)
      maintained in captivity under natural photoperiod (40 degrees 25'N).
      Concentrations of progesterone in the peripheral blood were determined by
      radioimmunoassay in samples collected from the jugular vein twice a week. First
      ovulations in the breeding season were highly synchronized and occurred in mid
      October. In contrast, the cessation of ovulatory cycles showed significant
      variation among females and extended from February to May, depending on age, with
      2-yr-old animals exhibiting the longest anovulatory period (P < 0.01). When
      lambing occurred within the breeding season (February-April), 12 out of 26
      animals had their first ovulation 25 +/- 1.8 days after parturition. The 14 late
      lambing females had the first postpartum ovulation delayed until the next
      breeding season. March/April-born mouflon lambs that reached a minimum threshold
      body weight (23.8 +/- 0.6 kg) in their first breeding season reached puberty at 8
      mo of age. In those with slower growth rates, however, the prepubertal period was
      extended throughout the first breeding and nonbreeding seasons, reaching puberty
      during the breeding season of the following year at 19 mo of age and 27 +/- 0.3
      kg body weight. Further, attainment of puberty in ewe lambs born in June/July was
      also delayed until the breeding season of the following year, when animals had
      reached a threshold body weight at 17 mo of age.

PMID- 12790425
TI  - Pharmacodynamics of flunixin and ketoprofen in mallard ducks (Anas
      platyrhynchos).
AB  - Flunixin (FLX) and ketoprofen (KET) are potent nonsteroidal anti-inflammatory
      drugs (NSAIDs) used to alleviate pain and decrease inflammation. These drugs
      block access of arachidonic acid to its binding site on the cyclooxygenase
      enzyme, thus preventing conversion to thromboxane A2 and subsequent degradation
      to thromboxane B2 (TBX). Consequently, plasma TBX may be used to estimate
      duration of NSAID action. Sixteen adult mallard ducks (Anas platyrhynchos) were
      randomly assigned to three treatment groups: control (n = 4), FLX 5 mg/kg (n =
      6), or KET 5 mg/kg (n = 6). Blood samples were taken 1 hr prior to and just
      before (0 hr) injection and 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, and 48 hr after
      injection. Plasma samples were analyzed for corticosterone and TBX. The feces
      were tested for the presence of hemoglobin and the ducks were euthanized for
      complete necropsy at the end of the study. Samples of muscle, kidney, liver,
      proventriculus, and intestine were taken for histologic analysis. Thromboxane was
      suppressed significantly in all birds following administration of either FLX or
      KET for 4 hr and decreased for approximately 12 hr compared with baseline samples
      (-1 and 0 hr). In the control group, TBX gradually declined over time. None of
      the ducks showed evidence of gastrointestinal bleeding, but the FLX group had
      muscle necrosis present at injection sites. FLX and KET likely exert
      pharmacological effects for at least 12 h. Although degree of TBX inhibition
      cannot be correlated absolutely with degree of analgesia or anti-inflammatory
      effects, it is possible that these effects are present during this time. This
      work suggests that FLX and KET can potentially be used as anti-inflammatory and
      analgesic agents in waterfowl. However, because of muscle necrosis at the
      injection site, we do not recommend parenteral use of FLX in ducks.

PMID- 12790427
TI  - Unilateral proptosis and orbital cellulitis in eight African hedgehogs (Atelerix
      albiventris).
AB  - Eight African hedgehogs (Atelerix albiventris) were presented with unilateral
      proptosis. Six animals presented specifically for an ocular problem, whereas two
      had concurrent neurologic disease. Enucleation and light microscopic examination
      of tissues was performed in five animals, and euthanasia followed by complete
      postmortem examination was performed in three animals. Histopathologic findings
      in all hedgehogs included orbital cellulitis, panophthalmitis, and corneal
      ulceration, with perforation in seven of eight eyes. The etiology of the orbital
      cellulitis was not determined, but it appeared to precede proptosis. Orbits in
      hedgehogs are shallow and the palpebral fissures are large, which may predispose
      them to proptosis, similar to brachycephalic dogs. This clinical presentation was
      seen in 15% (8/54) of African hedgehogs presented to the Western College of
      Veterinary Medicine over a 2-yr period from January 1995 to December 1996 and
      warrants further investigation.

PMID- 12790428
TI  - Mycobacterium avium subsp. paratuberculosis infection in an addax (Addax
      nasomaculatus).
AB  - Mycobacterium avium subsp. paratuberculosis was cultured from a single fecal
      sample collected from a 10-yr-old, captive-bred male addax (Addax nasomaculatus).
      Attempts to confirm infection with additional fecal cultures, serology, semen
      culture, and tissue biopsy were unsuccessful. There were no gross lesions on
      necropsy. On histopathology there were neither acid-fast organisms nor
      microscopic changes suggestive of active or clinical Johne's disease.
      Mycobacterium avium subsp. paratuberculosis was isolated from four organ tissues:
      ileum, jejunum, colon, and mesenteric lymph node.

PMID- 12790429
TI  - Pyometra and uterine adenocarcinoma in a melengestrol acetate-implanted captive
      coati (Nasua nasua).
AB  - A 9-yr and 3-mo-old captive female coati (Nasua nasua) was implanted with
      melengestrol acetate for contraception for 4.5 yr prior to presentation. During
      her annual examination, purulent vaginal discharge and a palpably prominent
      uterus were identified. Ancillary diagnostic tests including hematology,
      cystocentesis, radiographs, and abdominal ultrasound were consistent with
      pyometra. An ovariohysterectomy was performed and histologic examination revealed
      pyometra and uterine adenocarcinoma, similar to pathology that has been
      associated with melengestrol acetate contraception in felids, canids, and
      primates. Given the potential association between melengestrol acetate and
      uterine pathology in this case, we recommend caution with melengestrol acetate
      use in procyonids.

PMID- 12790430
TI  - Acute pulmonary Sarcocystis falcatula-like infection in three Victoria crowned
      pigeons (Goura victoria) housed indoors.
AB  - Three free-roaming Victoria crowned pigeons (Goura victoria) housed in a
      completely enclosed tropical exhibit were found dead without antemortem signs of
      illness. The birds died within 9 days of each other. Gross necropsy revealed
      moderate pulmonary edema in all three birds. Histopathologic examination revealed
      pulmonary edema and pulmonary protozoal merozoites compatible with Sarcocystis
      spp., Toxoplasma gondii, or Neospora spp. infection. Immunohistochemical staining
      for T. gondii and Neospora spp. were negative. Immunohistochemical staining
      identified a Sarcocystis falcatula-like parasite in all three birds. It is
      suspected that new exhibit soil contaminated with feces from the Virginia opossum
      (Didelphis virginiana) was the source of the infective sporocysts.

PMID- 12790431
TI  - Teratoma in desert grassland whiptail lizards (Cnemidophorus uniparens).
AB  - The clinical, gross necropsy, and histopathology findings in two unrelated desert
      grassland whiptail lizards (Cnemidophorus uniparens) with teratoma are described.
      The desert grassland whiptail is a parthenogenic lizard species with a polyploid
      chromosomal complement. The chromosome composition of the teratomas from these
      lizards was not determined.

PMID- 12790432
TI  - Interstitial cell tumor in a black-and-white ruffed lemur (Varecia variegatus
      variegatus).
AB  - A 14.5-yr-old, male black-and-white ruffed lemur (Varecia variegatus variegatus)
      presented for acute enlargement of the left testicle and hemiscrotum. Physical
      examination also revealed poor pelage quality with short guard hairs, sparse
      undercoat, and areas of alopecia. Increased aggression was also reported. A
      unilateral, open orchiectomy was performed, with the left testicle, epidydymis,
      associated vaginal tunic, and attached spermatic cord removed. Microscopic
      evaluation was consistent with an interstitial cell tumor, with many morphologic
      features similar to this neoplasm in people. No overt histopathologic criteria of
      malignancy were present. Following orchiectomy, gradual improvement in pelage
      quality was noted and was considered almost normal by 5 mo postoperative. In
      contrast with the aggressive preoperative behavior, the lemur was extremely
      submissive for 3 mo following the surgery. Gradual return to normal behavior and
      social status occurred over the next 2 mo. Multiple follow-up examinations and
      radiographs revealed no evidence of metastasis, and biopsy of the remaining
      testicle 4 mo later revealed no evidence of neoplasia. Serial measurements of
      testosterone and estradiol revealed levels within the range of those for other
      ruffed lemurs, as were repeated measurements taken of the remaining testicle. At
      19 mo postoperative, the lemur had a coat quality considered nearly normal and
      maintained its historical social position in the lemur group without abnormal
      aggressive behavior.

PMID- 12790433
TI  - Persistent right aortic arch and aberrant left subclavian artery in a white
      Bengal tiger (Panthera tigris).
AB  - A 3-mo-old male white Bengal tiger (Panthera tigris) presented with the chief
      complaint of regurgitation of solid food since weaning at 2 mo of age. Compared
      with its littermates, the tiger was in poor body condition and weighed only 10.3
      kg when its littermates were estimated at 20-25 kg. Thoracic radiographs showed a
      megaesophagus cranial to the heart base. A contrast esophagram more clearly
      outlined the megaesophagus, and fluoroscopy demonstrated normal motility of the
      caudal esophagus. Endoscopic examination revealed a structure coursing dorsally
      from right to left over the esophagus and a constrictive band on the left of the
      esophagus at the heart base. Nonselective angiography confirmed the presence of a
      persistent right aortic arch, as well as an aberrant left subclavian artery. A
      left fourth intercostal thoracotomy was performed, and the ligamentum arteriosum
      was double ligated and divided. The left subclavian artery did not cause
      significant compromise of the esophagus and was not manipulated at surgery. The
      tiger recovered well from anesthesia and surgery. Solid food was slowly
      introduced over a 2-mo period without any regurgitation. The cub gained weight
      rapidly after surgery.

PMID- 12790434
TI  - Clinical challenge. Dermestid beetle larvae (Coleoptera, Dermestidae).

PMID- 12790435
TI  - Microscopic origin of light scattering in tissue.
AB  - A newly designed instrument, the static light-scattering (SLS) microscope, which
      combines light microscopy with SLS, enables us to characterize local light
      scattering patterns of thin tissue sections. Each measurement is performed with
      an illumination beam of 70-microm diameter. On these length scales, tissue is not
      homogeneous. Both structural ordering and small heterogeneities contribute to the
      scattering signal. Raw SLS data consist of a two-dimensional intensity
      distribution map I(theta, phi), showing the dependence of the scattered intensity
      I on the scattering angle theta and the azimuthal angle phi. In contrast to the
      majority of experiments and to simulations that consider only the scattering
      angle, we additionally perform an analysis of the azimuthal dependence I(phi). We
      estimate different contributions to the azimuthal scattering variation and show
      that a significant fraction of the azimuthal amplitude is the result of tissue
      structure. As a demonstration of the importance of the structure-dependent part
      of the azimuthal signal, we show that this function of the scattered light alone
      can be used to classify tissue types with surprisingly high specificity and
      sensitivity.

PMID- 12790436
TI  - Monte Carlo prediction of near-infrared light propagation in realistic adult and
      neonatal head models.
AB  - In near-infrared spectroscopy and imaging, the sensitivity of the detected signal
      to brain activation and the volume of interrogated tissue are clinically
      important. Light propagation in adult and neonatal heads is strongly affected by
      the presence of a low-scattering cerebrospinal fluid layer. The effect of the
      heterogeneous structure of the head on light propagation in the adult brain is
      likely to be different from that in the neonatal brain because the thickness of
      the superficial tissues and the optical properties of the brain of the neonatal
      head are quite different from those of the adult head. In this study, light
      propagation in the two-dimensional realistic adult and neonatal head models,
      whose geometries are generated from a magnetic resonance imaging scan of the
      human heads, is predicted by Monte Carlo simulation. The sandwich structure,
      which is a low-scattering cerebrospinal fluid layer held between the high
      scattering skull and gray matter, strongly affects light propagation in the brain
      of the adult head. The sensitivity of the absorption change in the gray matter is
      improved; however, the intensely sensitive region is confined to the shallow
      region of the gray matter. The high absorption of the neonatal brain causes a
      similar effect on light propagation in the head. The intensely sensitive region
      in the neonatal brain is confined to the gray matter; however, the spatial
      sensitivity profile penetrates into the deeper region of the white matter.

PMID- 12790437
TI  - Hybrid Monte Carlo-diffusion method for light propagation in tissue with a low
      scattering region.
AB  - The heterogeneity of the tissues in a head, especially the low-scattering
      cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown
      to strongly affect light propagation in the brain. The radiosity-diffusion
      method, in which the light propagation in the CSF layer is assumed to obey the
      radiosity theory, has been employed to predict the light propagation in head
      models. Although the CSF layer is assumed to be a nonscattering region in the
      radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in
      the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion
      method, is proposed to calculate the head models, including the low-scattering
      region in which the light propagation does not obey neither the diffusion
      approximation nor the radiosity theory. The light propagation in the high
      scattering region is calculated by means of the diffusion approximation solved by
      the finite-element method and that in the low-scattering region is predicted by
      the Monte Carlo method. The intensity and mean time of flight of the detected
      light for the head model with a low-scattering CSF layer calculated by the hybrid
      method agreed well with those by the Monte Carlo method, whereas the results
      calculated by means of the diffusion approximation included considerable error
      caused by the effect of the CSF layer. In the hybrid method, the time-consuming
      Monte Carlo calculation is employed only for the thin CSF layer, and hence, the
      computation time of the hybrid method is dramatically shorter than that of the
      Monte Carlo method.

PMID- 12790438
TI  - Ultrafast-laser-radiation transfer in heterogeneous tissues with the discrete
      ordinates method.
AB  - Here light propagation and radiation transfer of ultrafast laser pulses in
      heterogeneous biological tissues are simulated by use of the discrete-ordinates
      method (DOM). Formulations for solving the time-dependent radiation-transfer
      equation are deduced for three-dimensional geometries incorporating the Fresnel
      specularly reflecting boundary condition and characteristics of ultrafast laser
      pulses. The present method can treat both the incident laser intensity and the
      scattered radiation intensity from the walls of the targeted tissue as two
      components, i.e., a diffuse part and a specular part. Reflectivity at the tissue
      air interface is calculated by use of Snell's law and the Fresnel equation. The
      high-order S10 DOM method is found to be adequate for describing the propagation
      and transfer of ultrafast laser radiation in heterogeneous tissues. The time
      dependent radiation field in the tissue as well as the temporal radiation
      intensity profiles at the boundaries can be obtained simultaneously. The absolute
      values of the logarithmic slope of the temporal reflectance and transmittance at
      various detector positions are found to converge to a constant value in a
      homogeneous tissue model. With the inclusion of a small inhomogeneity, such a
      value will change in line with the property of the embedded inhomogeneity. The
      orientation of heterogeneity of the tissues also substantially affects the
      radiation intensity at the boundaries. The effect of the Fresnel boundary in the
      modeling is pronounced. The simulated transmitted signals are broadened and
      amplified under specularly reflecting boundary condition as compared with those
      under diffusely reflecting boundary conditions.

PMID- 12790439
TI  - Near-infrared light propagation in an adult head model. I. Modeling of low-level
      scattering in the cerebrospinal fluid layer.
AB  - Adequate modeling of light propagation in a human head is important for
      quantitative near-infrared spectroscopy and optical imaging. The presence of a
      nonscattering cerebrospinal fluid (CSF) that surrounds the brain has been
      previously shown to have a strong effect on light propagation in the head.
      However, in reality, a small amount of scattering is caused by the arachnoid
      trabeculae in the CSF layer. In this study, light propagation in an adult head
      model with discrete scatterers distributed within the CSF layer has been
      predicted by Monte Carlo simulation to investigate the effect of the small amount
      of scattering caused by the arachnoid trabeculae in the CSF layer. This low
      scattering in the CSF layer is found to have little effect on the mean optical
      path length, a parameter that can be directly measured by a time-resolved
      experiment. However, the partial optical path length in brain tissue that relates
      the sensitivity of the detected signal to absorption changes in the brain is
      strongly affected by the presence of scattering within the CSF layer. The
      sensitivity of the near-infrared signal to hemoglobin changes induced by brain
      activation is improved by the effect of a low-scattering CSF layer.

PMID- 12790440
TI  - Near-infrared light propagation in an adult head model. II. Effect of superficial
      tissue thickness on the sensitivity of the near-infrared spectroscopy signal.
AB  - It is important for near-infrared spectroscopy (NIRS) and imaging to estimate the
      sensitivity of the detected signal to the change in hemoglobin that results from
      brain activation and the volume of tissue interrogated for a specific source
      detector fiber spacing. In this study light propagation in adult head models is
      predicted by Monte Carlo simulation to investigate the effect of the superficial
      tissue thickness on the partial optical path length in the brain and on the
      spatial sensitivity profile. In the case of source-detector spacing of 30 mm, the
      partial optical path length depends mainly on the depth of the inner skull
      surface whereas the spatial sensitivity profile is significantly affected by the
      thickness of the cerebrospinal fluid layer. The mean optical path length that can
      be measured by time-resolved experiments increases when the skull thickness
      increases whereas the partial mean optical path length in the brain decreases
      when the skull thickness increases. These results indicate that it is not
      appropriate to use the mean optical path length as an alternative to the partial
      optical path length to compensate the NIRS signal for the difference in
      sensitivity caused by variation of the superficial tissue thickness.

PMID- 12790441
TI  - Haar transform analysis of photon time-of-flight measurements for quantification
      of optical properties in scattering media.
AB  - A method to independently quantify the absorption and the scattering properties
      of samples based on the analysis of the Haar transform (HT) of photon time-of
      flight (TOF) distributions is described. A series of reflectance photon TOF
      measurements were acquired from absorbing/scattering milk samples of known
      composition (0 < mu(a) < 0.025 mm(-1); 100 < mu(s) < 250 mm(-1)). The HT of the
      profiles was calculated, and the regression based on the most parsimonious subset
      of wavelets was determined by the genetic algorithm (GA). In addition, the
      utility of computing the logarithm of the profiles or of the absolute value of
      the wavelet coefficients before the GA was studied. Results show that the
      absorption coefficient could be estimated with a coefficient of variation (C.V.)
      of 6.7% and an r2 of 0.99 by use of the log of selected wavelets of frequency
      less than 800 MHz. Scattering coefficients were estimated with a C.V. of 2.3% and
      an r2 of 0.99 with the log of wavelets of frequency less than 400 MHz. The above
      results suggest that a simplified instrument based on low-frequency switches
      could be developed to quantify the optical properties of highly scattering media.

PMID- 12790442
TI  - Frequency-domain multiplexing system for in vivo diffuse light measurements of
      rapid cerebral hemodynamics.
AB  - A novel frequency-domain multiplexing system has been developed for in vivo
      measurements of rapid cerebral hemodynamics. The instrument operates in the
      frequency-domain with three optical wavelengths, six source positions, and two
      detectors. Frequency-division multiplexing was used to modulate three wavelengths
      (690, 786, and 830 nm) at slightly different frequencies around 70 MHz. The three
      laser output beams were combined and switched into different source positions by
      use of fast optical switches (switch time <10 ms). Three narrowband, in-phase and
      in-quadrature demodulators decode the modulated signals. Our full-frame
      acquisition rate is 2.5 Hz, with flexibility for acquisition rates greater than
      50 Hz with smaller detection areas. We evaluate the performance of the instrument
      with tissue phantoms, and then employ the system to measure in vivo cerebral
      blood oxygenation during forepaw stimulation of a rat's brain.

PMID- 12790443
TI  - In vivo quantification of optical contrast agent dynamics in rat tumors by use of
      diffuse optical spectroscopy with magnetic resonance imaging coregistration.
AB  - We present a study of the dynamics of optical contrast agents indocyanine green
      (ICG) and methylene blue (MB) in an adenocarcinoma rat tumor model. Measurements
      are conducted with a combined frequency-domain and steady-state optical technique
      that facilitates rapid measurement of tissue absorption in the 650-1000-nm
      spectral region. Tumors were also imaged by use of contrast-enhanced magnetic
      resonance imaging (MRI) and coregistered with the location of the optical probe.
      The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin,
      and water are measured simultaneously each second for approximately 10 min. The
      differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise
      from differences in their effective molecular weights. ICG, because of its
      binding to plasma proteins, behaves as a macromolecular contrast agent with a low
      vascular permeability. A compartmental model describing ICG dynamics is used to
      quantify physiologic parameters related to capillary permeability. In contrast,
      MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the
      vasculature into the extravascular, extracellular space, and is sensitive to
      blood flow and the arterial input function.

PMID- 12790444
TI  - Coregistration of diffuse optical spectroscopy and magnetic resonance imaging in
      a rat tumor model.
AB  - We report coregistration of near-infrared diffuse optical spectroscopy (DOS) and
      magnetic resonance imaging (MRI) for the study of animal model tumors. A combined
      broadband steady-state and frequency-domain apparatus was used to determine
      tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors.
      Simultaneous MRI coregistration provided structural (T2-weighted) and contrast
      enhanced images of the tumor that were correlated with the optical measurements.
      By use of Monte Carlo simulations, the optically sampled volume was superimposed
      on the MR images, showing precisely which tissue structure was probed optically.
      DOS and MRI coregistration measurements were performed on seven rats over 20 days
      and were separated into three tumor tissue classifications: viable, edematous,
      and necrotic. A ratio of water concentration to total hemoglobin concentration,
      as measured optically, was performed for each tissue type and showed values for
      edematous tissue to be greater than viable tissue (1.2 +/- 0.49 M/microM versus
      0.48 +/- 0.15 M/microM). Tissue hemoglobin oxygen saturation (StO2) also showed a
      large variation between tissue types: viable tissue had an optically measured
      StO2 value of 61 +/- 5%, whereas StO2 determined for necrotic tissue was 43 +/-
      6%.

PMID- 12790445
TI  - Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge
      monitored with three oxygen-sensitive parameters.
AB  - The simultaneous measurement of three oxygen-sensitive parameters [arterial
      hemoglobin oxygen saturation (SaO2), tumor vascular-oxygenated hemoglobin
      concentration ([HbO2]), and tumor oxygen tension (pO2)] in response to hyperoxic
      respiratory challenge is demonstrated in rat breast tumors. The effects of two
      hyperoxic gases [oxygen and carbogen (5% CO2 and 95% O2)] were compared, by use
      of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in
      pedicles on the foreback. Two different gas-inhalation sequences were compared,
      i.e., air-carbogen-air-oxygen-air and air-oxygen-air-carbogen-air. The results
      demonstrate that both of the inhaled, hyperoxic gases significantly improved the
      tumor oxygen status. All three parameters displayed similar dynamic response to
      hyperoxic gas interventions, but with different response times: the fastest for
      arterial SaO2, followed by biphasic changes in tumor vascular [HbO2], and then
      delayed responses for pO2. Both of the gases induced similar changes in vascular
      oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2] and
      mean pO2 showed a linear correlation with large standard deviations, which
      presumably results from global versus local measurements. Indeed, the pO2 data
      revealed hetergeneous regional response to hyperoxic interventions. Although
      preliminary near-infrared measurements had been demonstrated previously in this
      model, the addition of the pO2 optical fiber probes provides a link between the
      noninvasive relative measurements of vascular phenomena based on endogenous
      reporter molecules, with the quantitative, albeit, invasive pO2 determinations.

PMID- 12790446
TI  - Limited possibility for quantifying mean particle size by logarithmic light
      scattering spectroscopy.
AB  - Recent studies have shown that the slope of logarithmic scattering spectroscopy
      of a turbid medium is related to the sizes of the scattering particles within the
      turbid medium. Mie theory can be used to generate a logarithmic plot of the
      reduced-scattering coefficient versus wavelength. According to Nilsson et al.
      [Appl. Opt. 37, 1256 (1998)], the slope value of a linear fit of the logarithmic
      scattering spectroscopy between 600 and 1050 nm can be used for direct
      determination of particle size. We performed similar calculations using the
      Rayleigh-Gans approximation and obtained an analogous overall shape with
      additional sinusoidal features. Our calculations indicate a possible relationship
      between the slope and the particle size when the size is used to calculate the
      slope, namely, in the forward calculation. However, because of the sinusoidal
      pattern, the inverse calculation to obtain the particle size from the slope may
      be applied only for particles with a radius of <0.13 microm in combination with
      650-1050-nm light. Caution should be exercised when inverse calculation is
      performed to determine the scattering particle sizes in the range of radii >0.13
      microm, with the slope of logarithmic scattering spectroscopy within 650-1050 nm.

PMID- 12790447
TI  - Optical lever recording of displacements from activated lobster nerve bundles and
      Nitella internodes.
AB  - An optical lever was designed for studying physical displacements associated with
      electrophysiological activation of lobster nerve bundles. Stimulation current
      pulses generated a compound action potential volley, and upward physical
      displacements of <1 nm were recorded. The swelling displacement propagated in the
      same direction as the action potential volley, occurred simultaneously with the
      action potentials, and required 10 ms to relax after the electrical potential was
      restored. For comparison with previous reports, we also recorded the displacement
      of Nitella internodes associated with electrical stimulation. We found that a
      rapid swelling displacement (approximately 10 nm) was followed by a larger, slow
      shrinking displacement (approximately 100 nm).

PMID- 12790448
TI  - Optical path-length spectroscopy of incipient caries lesions in relation to
      quantitative light-induced fluorescence and lesion characteristics.
AB  - A basic understanding of the light-scattering processes that take place inside
      the dental tissue (either sound or carious) is obtained both with measurements of
      the photon path-length distribution of light inside such media and with Monte
      Carlo simulations. Furthermore, the following is investigated: the correlations
      between different momenta of the photon path-length distribution of light inside
      caries lesions, the fluorescence loss determined with quantitative light-induced
      fluorescence, and/or the demineralization and depth of caries lesions determined
      with transversal microradiography. It is concluded that (i) the light paths
      inside both carious and sound enamel are considerably influenced by the
      refractive-index contrast at the tooth surface; (ii) contrary to a previous
      hypothesis, the fluorescence loss is larger in lesions in which the average
      photon path length is longer; (iii) very good correlations are obtained between
      the optical characteristics and the physical parameters of lesions when the
      optical measurements are performed such that there is high refractive contrast at
      the tooth surface.

PMID- 12790449
TI  - Convective-diffusion-based fluorescence correlation spectroscopy for detection of
      a trace amount of E. coli in water.
AB  - Fluorescence correlation spectroscopy (FCS) is adapted for a new procedure to
      detect trace amounts of Escherichia coli in water. The present concept is based
      on convective diffusion rather than Brownian diffusion and employs confocal
      microscopy as in traditional FCS. With this system it is possible to detect
      concentrations as small as 1.5 x 10(5) E. coli per milliliter (2.5 x 10(-16) M).
      This concentration corresponds to an approximately 1.0-nM level of Rhodamine 6G
      dyes. A detailed analysis of the optical system is presented, and further
      improvements for the procedure are discussed.

PMID- 12790450
TI  - Studying biological tissue with fluorescence lifetime imaging: microscopy,
      endoscopy, and complex decay profiles.
AB  - We have applied fluorescence lifetime imaging (FLIM) to the autofluorescence of
      different kinds of biological tissue in vitro, including animal tissue sections
      and knee joints as well as human teeth, obtaining two-dimensional maps with
      functional contrast. We find that fluorescence decay profiles of biological
      tissue are well described by the stretched exponential function (StrEF), which
      can represent the complex nature of tissue. The StrEF yields a continuous
      distribution of fluorescence lifetimes, which can be extracted with an inverse
      Laplace transformation, and additional information is provided by the width of
      the distribution. Our experimental results from FLIM microscopy in combination
      with the StrEF analysis indicate that this technique is ready for clinical
      deployment, including portability that is through the use of a compact picosecond
      diode laser as the excitation source. The results obtained with our FLIM
      endoscope successfully demonstrated the viability of this modality, though they
      need further optimization. We expect a custom-designed endoscope with optimized
      illumination and detection efficiencies to provide significantly improved
      performance.

PMID- 12790451
TI  - Absorption coefficient imaging by near-field scanning optical microscopy in
      bacteria.
AB  - We present a method for obtaining a position-dependent absorption coefficient
      from near-field scanning optical transmission microscopy. We show that the
      optical transmission intensity can be combined with the topography, resulting
      into an absorption coefficient that simplifies the analysis of different
      materials within a sample. The method is tested with the dye rhodamine 6G, and we
      show some analysis in biological samples such as bacteria KIebsiella pneumoniae
      and Pseudomonas aeruginosa. The calculated absorption coefficient images show
      important details of the bacteria, in particular for P. aeruginosa, in which
      membrane vesicles are clearly seen.

PMID- 12790452
TI  - Techniques for fast and sensitive measurements of two-dimensional birefringence
      distributions.
AB  - We propose image processing algorithms for measuring two-dimensional
      distributions of linear birefringence using a pair of variable retarders. Several
      algorithms that use between two and five recorded frames allow us to optimize
      measurements for speed, sensitivity, and accuracy. We show images of asters,
      which consist of radial arrays of microtubule polymers recorded with a polarized
      light microscope equipped with a universal compensator. Our experimental results
      confirm our theoretical expectations. The lowest noise level of 0.036 nm was
      obtained when we used the five-frame technique and four-frame algorithm without
      extinction setting. The two-frame technique allows us to increase the speed of
      measurement with acceptable image quality.

PMID- 12790453
TI  - Submicrosecond speed optical coherence tomography system design and analysis by
      use of acousto-optics.
AB  - A novel high-speed no-moving-parts optical coherence tomography (OCT) system is
      introduced that acquires sample data at less than a microsecond per data point
      sampling rate. The basic principle of the proposed OCT system relies on use of an
      acousto-optic deflector. This OCT system has the attractive features of an
      acousto-optic scanning heterodyne interferometer coupled with an acousto-optic
      (AO) variable optical delay line operating in a reflective mode. Fundamentally,
      OCT systems use a broadband light source for high axial resolution inside the
      sample or living tissue under examination. Inherently, AO devices are Bragg-mode
      wavelength-sensitive elements. We identify that two beams generated by a Bragg
      cell naturally have unbalanced and inverse spectrums with respect to each other.
      This mismatch in spectrums in turn violates the ideal autocorrelation condition
      for a high signal-to-noise ratio broadband interferometric sensor such as OCT. We
      solve this fundamental limitation of Bragg cell use for OCT by deploying a new
      interferometric architecture where the two interfering beams have the same power
      spectral profile over the bandwidth of the broadband source. With the proposed AO
      based system, high (e.g., megahertz) intermediate frequency can be generated for
      low 1/f noise heterodyne detection. System issues such as resolution, number of
      axial scans, and delay-path selection time are addressed. Experiments described
      demonstrate our high-speed acousto-optically tuned OCT system where optical delay
      lines can be selected at submicrosecond speeds.

PMID- 12790454
TI  - Precision of measurement of tissue optical properties with optical coherence
      tomography.
AB  - Accurate and noninvasive measurement of tissue optical properties can be used for
      biomedical diagnostics and monitoring of tissue analytes. Noninvasive measurement
      of tissue optical properties (total attenuation and scattering coefficients,
      optical thickness, etc.) can be performed with the optical coherence tomography
      (OCT) technique. However, speckle noise substantially deteriorates the accuracy
      of the measurements with this technique. We studied suppression of speckle noise
      for accurate measurement of backscattering signal and scattering coefficient with
      the OCT technique. Our results demonstrate that the precision of measurement of
      backscattering signals with the OCT technique can be 0.2% for homogeneously
      scattering media and 0.7% for skin, if spatial averaging of speckle noise is
      applied. This averaging allows us to achieve the precision of tissue scattering
      coefficient measurements of approximately +/-0.8%. This precision can be further
      improved by a factor of 2-3, upon optimization of OCT operating parameters.

PMID- 12790455
TI  - Autofocus algorithm for dispersion correction in optical coherence tomography.
AB  - Practical clinical optical coherence tomography (OCT) systems require automatic
      tools for identifying and correcting flaws in OCT images. One type of flaw is the
      loss of image detail owing to the dispersion of the medium, which in most cases
      is unknown. We present an autofocus algorithm for estimating the delay line and
      material dispersion from OCT reflectance data, integrating a previously presented
      dispersion compensation algorithm to correct the data. The algorithm is based on
      minimizing the Renyi entropy of the corrected axial-scan image, which is a
      contrast-enhancement criterion. This autofocus algorithm can be used in
      conjunction with a high-speed, digital-signal-processor-based OCT acquisition
      system for rapid image correction.

PMID- 12790456
TI  - Automated detection of ocular alignment with binocular retinal birefringence
      scanning.
AB  - We previously developed a retinal birefingence scanning (RBS) device to detect
      eye fixation. The purpose of this study was to determine whether a new binocular
      RBS (BRBS) instrument can detect simultaneous fixation of both eyes. Control
      (nonmyopic and myopic) and strabismic subjects were studied by use of BRBS at a
      fixation distance of 45 cm. Binocularity (the percentage of measurements with
      bilateral fixation) was determined from the BRBS output. All nonstrabismic
      subjects with good quality signals had binocularity >75%. Binocularity averaged
      5% in four subjects with strabismus (range of 0-20%). BRBS may potentially be
      used to screen individuals for abnormal eye alignment.

PMID- 12790457
TI  - Optical topography: practical problems and new applications.
AB  - We will briefly review the present status of optical topography and then discuss
      the method of improving practicality, i.e., the signal-to-noise (S/N) ratio and
      the spatial resolution in observations of higher-order brain functions. The
      optimum wavelength pair improved the S/N ratio sixfold for deoxyhemoglobin, and
      new configurations of light irradiation and detection positions doubled the
      spatial resolution. We also report on developing application fields of optical
      topography. This modality will bridge the gap between natural sciences,
      neuroscience, and pedagogy, and show actual real-time brain activity.

PMID- 12790458
TI  - Characterization of spatial and temporal variations in the optical properties of
      tissuelike media with diffuse reflectance imaging.
AB  - We describe a method to characterize spatial or temporal changes in the optical
      properties of turbid media using diffuse reflectance images acquired under broad
      beam illumination conditions. We performed experiments on liquid phantoms whose
      absorption (mu(a)) and reduced scattering (mu(s)') coefficients were
      representative of those of biological tissues in the near infrared. We found that
      the relative diffuse reflectance R depends on mu(a) and mu(s)' only through the
      ratio mu(a)/mu(s)' and that dependence can be well described with an analytical
      expression previously reported in the literature [S. L. Jacques, Kluwer Academic
      Dordrecht (1996)]. We have found that this expression for R deviates from
      experimental values by no more than 8% for various illumination and detection
      angles within the range 0 degrees-30 degrees. Therefore, this analytical
      expression for R holds with good approximation even if the investigated medium
      presents curved or irregular surfaces. Using this expression, it is possible to
      translate spatial or temporal changes in the relative diffuse reflectance from a
      turbid medium into quantitative estimates of the corresponding changes of
      (mu(a)/mu(s)')(1/2). In the case of media with optical properties similar to
      those of tissue in the near infrared, we found that the changes mu(a)/mu(s)'
      should occur over a volume approximately 2 mm deep and 4 mm x 4 mm wide to apply
      this expression.

PMID- 12790459
TI  - In vivo quantitative three-dimensional localization of tumor labeled with
      exogenous specific fluorescence markers.
AB  - We introduce a diffused optical detection system based on the administration of a
      fluorophore-antibody conjugate to diseased tissue. The conjugate interacts with
      the antigens expressed by the diseased tissue, resulting in fluorescent labeling
      of the antigen. By combining an optical detection system with a reconstruction
      algorithm developed on the basis of the random-walk model, we were able to
      determine the position of the fluorophore (and, thus, of the diseased cells) in
      the tissue. We present three-dimensional reconstructions of the location of a
      fluorophore (FITC-fluorescein isothiocyanate) in the tongues of mice.
      Measurements were performed with the fluorophore embedded at various simulated
      depths. The simulations were performed with agarose-based gel slabs applied to
      the tongue as tissuelike phantoms. Reconstructed fluorophore locations agree well
      with the actual values.

PMID- 12790460
TI  - Fluorescence optical diffusion tomography.
AB  - A nonlinear, Bayesian optimization scheme is presented for reconstructing
      fluorescent yield and lifetime, the absorption coefficient, and the diffusion
      coefficient in turbid media, such as biological tissue. The method utilizes
      measurements at both the excitation and the emission wavelengths to reconstruct
      all unknown parameters. The effectiveness of the reconstruction algorithm is
      demonstrated by simulation and by application to experimental data from a tissue
      phantom containing the fluorescent agent Indocyanine Green.

PMID- 12790461
TI  - Robust inference of baseline optical properties of the human head with three
      dimensional segmentation from magnetic resonance imaging.
AB  - We model the capability of a small (6-optode) time-resolved diffuse optical
      tomography (DOT) system to infer baseline absorption and reduced scattering
      coefficients of the tissues of the human head (scalp, skull, and brain). Our
      heterogeneous three-dimensional diffusion forward model uses tissue geometry from
      segmented magnetic resonance (MR) data. Handling the inverse problem by use of
      Bayesian inference and introducing a realistic noise model, we predict
      coefficient error bars in terms of detected photon number and assumed model
      error. We demonstrate the large improvement that a MR-segmented model can
      provide: 2-10% error in brain coefficients (for 2 x 10(6) photons, 5% model
      error). We sample from the exact posterior and show robustness to numerical model
      error. This opens up the possibility of simultaneous DOT and MR for quantitative
      cortically constrained functional neuroimaging.

PMID- 12790462
TI  - Optical tomography of a realistic neonatal head phantom.
AB  - We have begun clinical trials of optical tomography of the neonatal brain. To
      validate this research, we have built and imaged an anatomically realistic,
      tissue-equivalent neonatal head phantom that is hollow, allowing contrasting
      objects to be placed inside it. Images were reconstructed by use of two finite
      element meshes, one generated from a computed tomography image of the phantom and
      the other spherical. The phantom was filled with a liquid of the same optical
      properties as the outer region, and two perturbations were placed inside. These
      were successfully imaged with good separation between the absorption and scatter
      coefficients. The phantom was then refilled with a liquid of increased absorption
      compared with the background to simulate the brain, and the absolute properties
      of the two regions were found. These were used as a priori information for the
      complete reconstruction. Both perturbations were visible, superimposed on the
      increased absorption of the central region. The head-shaped mesh performed
      slightly better than the spherical mesh, particularly when the absorption of the
      central region of the phantom was increased.

PMID- 12790463
TI  - Three-dimensional optical tomography: resolution in small-object imaging.
AB  - Near-infrared (NIR) optical tomography provide estimates of the internal
      distribution of optical absorption and transport scattering from boundary
      measurement of light propagation within biological tissue. Although this is a
      truly three-dimensional (3D) imaging problem, most research to date has
      concentrated on two-dimensional modeling and image reconstruction. More recently,
      3D imaging algorithms are demonstrating better estimation of the light
      propagation within the imaging region and are providing the basis of more
      accurate image construction algorithms. As 3D methods emerge, it will become
      increasingly important to evaluate their resolution, contrast, and localization
      of optical property heterogeneity. We present a concise study of 3D reconstructed
      resolution of a small, low-contrast, absorbing and scattering anomaly as it is
      placed in different locations within a cylindrical phantom. The object is an 8-mm
      diameter cylinder, which represents a typical small target that needs to be
      resolved in NIR mammographic imaging. The best resolution and contrast is
      observed when the object is located near the periphery of the imaging region (12
      22 mm from the edge) and is also positioned within the multiple measurement
      planes, with the most accurate results seen for the scatter image when the
      anomaly is at 17 mm from the edge. Furthermore, the accuracy of quantitative
      imaging is increased to almost 100% of the target values when a priori
      information regarding the internal structure of imaging domain is utilized.

PMID- 12790464
TI  - Three-dimensional shape-based imaging of absorption perturbation for diffuse
      optical tomography.
AB  - We present a shape-based approach to three-dimensional image reconstruction from
      diffuse optical data. Our approach differs from others in the literature in that
      we jointly reconstruct object and background characterization and localization
      simultaneously, rather than sequentially process for optical properties and
      postprocess for edges. The key to the efficiency and robustness of our algorithm
      is in the model we propose for the optical properties of the background and
      anomaly: We use a low-order parameterization of the background and another for
      the interior of the anomaly, and we use an ellipsoid to describe the boundary of
      the anomaly. This model has the effect of regularizing the inversion problem and
      provides a natural means of including additional physical properties if they are
      known a priori. A Gauss-Newton-type algorithm with line search is implemented to
      solve the underlying nonlinear least-squares problem and thereby determine the
      coefficients of the parameterizations and the descriptors of the ellipsoid.
      Numerical results show the effectiveness of this method.

PMID- 12790465
TI  - Experimental test of a perturbation model for time-resolved imaging in diffusive
      media.
AB  - We report what to our knowledge is a novel perturbation approach for time
      resolved transmittance imaging in diffusive media, based on the diffusion
      approximation with extrapolated boundary conditions. The model relies on the
      method of Pade approximants and consists of a nonlinear approximation of time
      resolved transmittance curves in the presence of an inclusion. The proposed model
      is intended to extend the range of applicability of perturbation models when
      applied to inclusions that are non-point-like. We test the model on different
      tissue phantoms with scattering only, absorbing only, and both scattering and
      absorbing inclusions. Maps of the optical properties are displayed, and the
      results are compared with those obtained by means of the usual linear
      approximation of time-resolved transmittance curves. We found that the nonlinear
      approach gives a better prediction for absolute values of the scattering and
      absorption coefficients of inclusions, when the inclusion optical properties are
      higher than the surrounding background. Furthermore, better-resolved spots and a
      reduced cross talk between the two parameters are found in the reconstructed
      maps. Because the range of the optical properties spanned by the considered
      phantoms covers the values expected for optical mammography, the application of
      the reported reconstruction method to in vivo images of a breast appears
      promising from a diagnostic viewpoint.

PMID- 12790466
TI  - Optode positional calibration in diffuse optical tomography.
AB  - Although diffuse optical tomography is a highly promising technique used to
      noninvasively image blood volume and oxygenation, the reconstructed data are
      sensitive to systemic difference between the forward model and the actual
      experimental conditions. In particular, small changes in optode location or in
      the optode-tissue coupling coefficient significantly degrade the quality of the
      reconstruction images. Accurate system calibration therefore is an essential part
      of any experimental protocol. We present a technique for simultaneously
      calibrating optode positions and reconstructing images that significantly
      improves image quality, as we demonstrate with simulations and phantom
      experiments.

PMID- 12790467
TI  - In vivo breast imaging with diffuse optical tomography based on higher-order
      diffusion equations.
AB  - We report on in vivo absorption and scattering imaging of a human breast cyst and
      implant, using a reconstruction algorithm based on our third-order diffusion
      equations. To validate these in vivo images, a series of phantom experiments were
      conducted, in which we used low-absorbing and low-scattering heterogeneities to
      mimic a breast cyst or implant. These heterogeneities or targets were composed of
      pure water or a mixture of water and very dilute Intralipid (0.05% and 0.1%). The
      phantom experiment confirmed the quantitative imaging capability of our improved
      algorithm for reconstructing heterogeneities where the conventional diffusion
      approximation is inadequate. Pilot clinical results from female volunteers
      indicate that enhanced diffuse optical tomography can quantitatively image
      findings such as breast cysts or implants in which the absorption and scattering
      coefficients are usually low.

PMID- 12790468
TI  - Time-domain optical mammography: initial clinical results on detection and
      characterization of breast tumors.
AB  - Mammograms of 35 patients suspected of breast cancer were taken along
      craniocaudal and mediolateral projections with a dual-wavelength scanning laser
      pulse mammograph measuring time-resolved transmittance. Among 26 tumors known
      from routine clinical diagnostics, 17 tumors were detected retrospectively in
      optical mammograms. Effective tumor optical properties derived from a homogeneous
      model were used to deduce physiological information. All tumors exhibited
      increased total hemoglobin concentration and decreased or unchanged blood oxygen
      saturation compared with surrounding healthy tissue. Scatter plots based on a
      pixelwise analysis of individual mammograms were introduced and applied to
      represent corelations between characteristic quantities derived from measured
      distributions of times of flight of photons.

PMID- 12790470
TI  - Influence of perfusion depth on laser Doppler flow measurements with large source
      detector spacing.
AB  - Laser Doppler flowmetry with a large source-detector spacing has been applied to
      measure blood perfusion in the deeper regions of tissue. The influence of the
      depth of perfusion on the Doppler spectrum for the large source-detector spacing
      is likely to be different from that for the conventional laser Doppler
      instruments with small source-detector spacing. In this study, the light
      propagation in a tissue model with a blood perfusion layer is predicted by the
      Monte Carlo simulation to discuss the influence of the depth of perfusion, blood
      volume, and source-detector spacing on the spectrum of the Doppler signal
      detected with large source-detector spacing. The influence of the depth of
      perfusion on the Doppler spectrum for the large source-detector spacing is
      different from that for the conventional laser Doppler instruments with small
      source-detector spacing, although the influence of source-detector spacing and
      blood volume on the Doppler spectrum for large source-detector spacing is almost
      the same as that for the conventional laser Doppler instruments. The influence of
      the depth of the perfusion on the Doppler spectrum depends on the path length
      that the detected light travels at different depths.

PMID- 12790469
TI  - Collection efficiency of a single optical fiber in turbid media.
AB  - If a single optical fiber is used for both delivery and collection of light, two
      major factors affect the measurement of collected light: (1) the light transport
      in the medium that describes the amount of light that returns to the fiber and
      (2) the light coupling to the optical fiber that depends on the angular
      distribution of photons entering the fiber. We focus on the importance of the
      latter factor and describe how the efficiency of the coupling depends on the
      optical properties of the medium. For highly scattering tissues, the efficiency
      is well predicted by the numerical aperture (NA) of the fiber. For lower
      scattering, such as in soft tissues, photons arrive at the fiber from deeper
      depths, and the coupling efficiency could increase twofold to threefold above
      that predicted by the NA.

PMID- 12790471
TI  - Catheter for diagnosis and therapy with infrared evanescent waves.
AB  - We have developed an optical delivery device (catheter) capable of transmitting
      broadband infrared light (IR wavelengths from 2 to 10 microm) for both diagnostic
      and therapeutic applications. The catheter is 1.68 mm in outer diameter and 1 m
      in length. It consists of two hollow glass waveguides coupled to a high
      refractive-index optic tip. The IR light interacts with the tissue at the optic
      tissue interface to measure the spectral signatures and perform therapy on the
      tissue at this interface. Fourier-transform IR spectrophotometer light is used to
      obtain the spectral signatures, and an IR free-electron laser (FEL) is used to
      study the therapeutic interaction of evanescent waves with the tissue. We present
      our catheter design; preliminary IR spectroscopy of aorta, blood, fatty tissue,
      and muscle; and IR FEL therapy on atheroslerotic aorta.

PMID- 12790472
TI  - In vivo port-wine stain depth determination with a photoacoustic probe.
AB  - We have designed a photoacoustic probe for port-wine stain (PWS) depth
      measurements consisting of optical fibers for laser light delivery and a
      piezoelectric element for acoustic detection. We characterized the capabilities
      and limitations of the probe for profiling PWS skin. The probe induced and
      measured photoacoustic waves in acrylamide tissue phantoms and PWS skin in vivo.
      The optical properties of the phantoms were chosen to mimic those of PWS skin. We
      denoised acoustic waves using spline wavelet transforms, then deconvolved with
      the impulse response of the probe to yield initial subsurface pressure
      distributions in phantoms and PWS skin. Using the phantoms, we determined that
      the limit in resolving epidermal and PWS layers was less than 70 microm. In
      addition, we used the phantoms to determine that the maximum epidermal melanin
      concentration that allowed detection of PWS was between 13 and 20%. In vivo
      measurements of PWS skin with different epidermal melanin concentrations
      correlated with the phantoms. Thus the photoacoustic probe can be used to
      determine PWS depth for most patients receiving laser therapy.

PMID- 12790473
TI  - Controlling the spectral response in guided-mode resonance filter design.
AB  - Techniques for controlling spectral width are used in conjunction with thin-film
      techniques in the design of guided-mode resonance (GMR) filters to provide
      simultaneous control over line-shape symmetry, sideband levels, and spectral
      width. Several factors that could limit the minimum spectral width are discussed.
      We used interference effects for passband shaping by stacking multiple GMR
      filters on top of one another. A design is presented for a 200-GHz
      telecommunications filter along with a tolerance analysis. Compared with a
      conventional thin-film filter, the GMR filter has fewer layers and looser
      thickness tolerances. Grating fabrication tolerances are also discussed.

PMID- 12790474
TI  - Optical measurement of depth and duty cycle for binary diffraction gratings with
      subwavelength features.
AB  - We describe a new and unique method for simultaneous determination of the groove
      depth and duty cycle of binary diffraction gratings. For a near-normal angle of
      incidence, the +1 and -1 diffracted orders will behave nearly the same as the
      duty cycle is varied for a fixed grating depth. The difference in their behavior,
      quantified as the ratio of their respective diffraction efficiencies, is compared
      to a look-up table generated by rigorous coupled-wave theory, and the duty cycle
      of the grating is thus obtained as a function of grating depth. Performing the
      same analysis for the orthogonal probe-light polarization results in a different
      functional dependence of the duty cycle on the grating depth. By use of both TE
      and TM polarizations, the depth and duty cycle for the grating are obtained by
      the intersection of the functions generated by the individual polarizations.
      These measurements can also be used to assess qualitatively both the uniformity
      of the grating and the symmetry of the grating profile. Comparison with scanning
      electron microscope images shows excellent agreement. This method is advantageous
      since it can be carried out rapidly, is accurate and repeatable, does not damage
      the sample, and uses low-cost, commonly available equipment. Since this method
      consists of only four fixed simple measurements, it is highly suitable for
      quality control in a manufacturing environment.

PMID- 12790475
TI  - Fiber Fabry-Perot sensors for detection of partial discharges in power
      transformers.
AB  - A diaphragm-based interferometric fiberoptic sensor that uses a low-coherence
      light source was designed and tested for on-line detection of the acoustic waves
      generated by partial discharges inside high-voltage power transformers. The
      sensor uses a fused-silica diaphragm and a single-mode optical fiber encapsulated
      in a fused-silica glass tube to form an extrinsic Fabry-Perot interferometer,
      which is interrogated by low-coherence light. Test results indicate that these
      fiber optic acoustic sensors are capable of faithfully detecting acoustic signals
      propagating inside transformer oil with high sensitivity and wide bandwidth.

PMID- 12790476
TI  - Erbium-doped optical fiber fluorescence temperature sensor with enhanced
      sensitivity, a high signal-to-noise ratio, and a power ratio in the 520-530- and
      550-560-nm bands.
AB  - We analyze and predict the performance of a fiber-optic temperature sensor from
      the measured fluorescence spectrum to optimize its design. We apply this analysis
      to an erbium-doped silica fiber by employing the power-ratio technique. We
      develop expressions for the signal-to-noise ratio in a band to optimize sensor
      performance in each spectral channel. We improve the signal-to-noise ratio by a
      factor of 5 for each channel, compared with earlier results. We evaluate the
      analytical expression for the sensor sensitivity and predict it to be
      approximately 0.02 degrees C(-1) for the temperature interval from room
      temperature to above 200 degrees C, increasing from 0.01 degrees C(-1) at the
      edges of the interval to 0.03 degrees C(-1) at the center, at 100-130 degrees C.
      The sensitivity again increases at temperatures higher than 300 degrees C,
      delineating its useful temperature intervals.

PMID- 12790477
TI  - Resolution limit for two-dimensional crossed-grating patterns projected by a
      coherent beam.
AB  - The resolution limit for two-dimensional crossed-grating patterns created by
      projecting mask objects by using a coherent beam has been investigated. We
      consider first two conventional mask types, a binary-amplitude mask and a two
      level phase-shifting mask, in analyzing relationships between a diffraction-beam
      configuration and an image-intensity distribution. Then we derive, as a mask that
      overcomes the resolution limit of the conventional ones, a four-level phase
      shifting structure with which the minimum image period can be reduced to square
      root(2)/2 time that of the two-level phase-shifting mask.

PMID- 12790478
TI  - Simple polarimetric approach to direct measurement of the near-surface refractive
      index in graded-index films.
AB  - In the standard M-line method for the characterization of graded-index film, an
      analytical curve is fitted to the waveguide mode measurements and extrapolated to
      provide the refractive index in the zero-depth limit. Here we review our
      polarimetric approach to a direct near-surface measurement, which complements the
      M-line method. Also, we present its new and more straightforward version, which
      is applicable to existing samples and does not require masking before ion
      exchange.

PMID- 12790479
TI  - Dependence of the Bragg condition on an external electric field for a polymeric
      photorefractive material.
AB  - We investigated the effect of an applied electric field on the Bragg condition of
      degenerate four-wave mixing a polymeric photorefractive material with a low glass
      transition temperatue. For a polymeric photorefractive material the application
      of an external electric field is necessary for photorefractivity leads to
      birefringence of the material by poling of the nonlinear optical chromophore.
      Because the propagation vectors of the pumping and reading beams inside the
      material are influenced by the refractive index of the material, the Bragg
      condition depends on the magnitude of the external field. Using an oriented gas
      model and the-coupled-mode theory, we numerically analyzed the Bragg-mismatch
      effect that causes a reduction in diffraction efficiency as a function of an
      external field. We present the boundary conditions for sample thickness and
      grating spacing for which the Bragg-mismatch effect must be taken into account.

PMID- 12790480
TI  - Confocal total-internal-reflection fluorescence microscopy with a high-aperture
      parabolic mirror lens.
AB  - We present a theoretical study of a new total-internal-reflection fluorescence
      microscope for the detection of fluorescence at a water-glass interface. The
      system is designed for confocal imaging and spectroscopy of nanoparticles and
      single molecules. Focusing and fluorescence collection through standard glass
      coverslips is accomplished by a parabolic mirror lens. The large aperture of the
      element is used to excite fluorescence within the evanescent field of a
      diffraction-limited focus and to collect focal emission with high efficiency.
      Tight focusing and supercritical excitation reduce the detection volume for
      fluorescent analyte molecules well below that of an attoliter (10(-18) L), which
      can be advantageous for monitoring surface binding of single molecules without
      interference from fluorescence of the unbound bulk. Calculations of the electric
      fields in the focus region and simulated confocal imaging demonstrate the
      performance of the system.

PMID- 12790481
TI  - Exact ray-trace beam for an off-axis paraboloid surface.
AB  - When an off-axis paraboloidal mirror focuses a parallel beam, the image is formed
      on one side of the optical axis. For a tilted beam focused by an off-axis
      paraboloidal mirror, the focus is no longer pointlike (not considering the
      diffraction effect); rather, it is a distorted spot. This is due to the inherent
      aberrations of the surface. In addition, there is a change in the focus position.
      We calculate by exact ray-trace equations the modified wave-front aberration and
      express it in power series. Our formulation uses the optical path variation along
      a defined principal ray that we relate to the parameter that describe the surface
      and the beam angle of incidence. We designate this ray as that reflected by the
      center of the entrance pupil and field of view. We employ the direction cosines
      of the principal ray to compute the wave-front aberration function of a beam
      reflected by an off-axis paraboloid.

PMID- 12790482
TI  - Structure and scattering properties of Ni80Nb20-MgO water-window multilayer
      mirrors.
AB  - Ni80Nb20-MgO multilayers with d spacing that varies from 2.50 to 3.07 nm were
      prepared by pulsed laser deposition under conditions of ultrahigh vacuum (UHV)
      and argon. The morphological and atomic structure in the multilayers was
      determined by hard-x-ray scattering. It was found that the interface roughness in
      both cases, UHV and argon deposition, is <0.4 nm, whereas the lateral and
      longitudinal correlation lengths in the case of argon deposition, 5.0 and 1.0 nm,
      respectively, are an order of magnitude lower. This is due to a reduction in
      kinetic energy of the condensing species in argon by orders of magnitude due to
      multiple collisions, which reduces the lateral relaxation probability. Hence the
      soft-x-ray reflectance of [Ni80Nb20-MgO]10 multilayers deposited in argon was
      determined at 413 eV (3.00 nm), middle of the water window. The reflectance has a
      peak at approximately 35.2 degrees with a half-width of 3.5 degrees and 0.19%
      maximum value. These results agree well with the simulation results performed by
      use of the structural parameters obtained from hard-x-ray scattering. The atomic
      structure determined by high-angle x-ray diffraction shows that both Ni80Nb20 and
      MgO are amorphous in the as-deposited condition.

PMID- 12790483
TI  - Design considerations for a highly segmented mirror.
AB  - Design issues for a 30-m highly segmented mirror are explored, with emphasis on
      parametric models of simple, inexpensive segments. A mirror with many small
      segments offers cost savings through quantity production and permits high-order
      active and adaptive wave-front corrections. For a 30-m f/1.5 paraboloidal mirror
      made of spherical, hexagonal glass segments, with simple warping harnesses and
      three-point supports, the maximum segment diameter is approximately 100 mm, and
      the minimum segment thickness is approximately 5 mm. Large-amplitude, low-order
      gravitational deformations in the mirror cell can be compensated if the segments
      are mounted on a plate floating on astatic supports. Because gravitational
      deformations in the plate are small, the segment actuators require a stroke of
      only a few tens of micrometers, and the segment positions can be measured by a
      wave-front sensor.

PMID- 12790484
TI  - Streak camera: a multidetector for diffuse optical tomography.
AB  - We describe an experimental setup for time-resolved diffuse optical tomography
      that uses a seven-channel light guide to transmit scattered light to a streak
      camera. This setup permits the simultaneous measurement of the time profiles of
      photons reemitted at different boundary sites of the objects studied. The
      instrument, its main specifications, and detector-specific data analysis before
      image reconstruction are described. The instrumentation was tested with phantoms
      simulating biological tissue, and the absorption and reduced scattering images
      that were obtained are discussed.

PMID- 12790485
TI  - Penetration depth of single-, two-, and three-photon fluorescence microscopic
      imaging through human cortex structures: Monte Carlo simulation.
AB  - Penetration depth is investigated in terms of the performance of transverse image
      resolution and signal level in human cortex under single-, two-, and three-photon
      fluorescence microscopy. Simulation results show that, in a double-layer human
      cortex structure consisting of gray and white matter media, the signal level is
      strongly affected by the existence of the white matter medium under three-photon
      excitation. Compared with three-photon excitation, two-photon excitation keeps a
      better signal level and sacrifices a slight degradation in image resolution. In a
      thick gray matter medium, a penetration depth of 1500 microm with a near
      diffraction-limited resolution is obtainable under three-photon excitation. It is
      also demonstrated that the numerical aperture has a slight influence on image
      resolution and signal level under two- and three-photon excitation because of the
      nonlinear nature in the excitation process.

PMID- 12790486
TI  - Involuntary cultural change, stress phenomenon and aboriginal health status.

PMID- 12790487
TI  - The health of Ontario First Nations people: results from the Ontario First
      Nations Regional Health Survey.
AB  - OBJECTIVE: To describe the health of First Nations adults residing on Ontario
      reserves using data from the Ontario First Nations Regional Health Survey
      (OFNRHS). METHOD: Communities were randomly selected; individuals were
      systematically selected based on gender and age. Health questions were parallel
      to those used in the National Population Health Survey (NPHS) and included
      general health, chronic conditions, substance use, and health service
      utilization. RESULTS: Response rate was 86% (N=1094) in participating
      communities; 23 of 30 selected communities participated. Most OFNRHS respondents
      reported that their health was good or better. Comparisons of OFNRHS participants
      with NPHS Ontario respondents showed: some chronic health conditions (including
      diabetes, high blood pressure) were more common; a greater proportion reported
      smoking; and a substantially lower proportion indicated that they consumed
      alcohol in the past year. CONCLUSIONS: The OFNRHS provides important province
      wide data to inform decisions by the First Nations people about how to intervene
      effectively to improve their health status.

PMID- 12790488
TI  - A review of Aboriginal women's physical and mental health status in Ontario.

PMID- 12790489
TI  - Hepatitis A among residents of First Nations Reserves in British Columbia, 1991
      1996.
AB  - BACKGROUND: Hepatitis A spreads by the fecal-oral route. We hypothesize that it
      is more common in Aboriginal communities because of poverty, crowded housing and
      inadequate or substandard water and sewage systems. METHODS: We tabulated on
      reserve cases reported to First Nations and Inuit Health Branch, Health Canada.
      We obtained information on community water supply, sewage disposal and mean
      population per housing unit, from site inspections in a 1994 survey. RESULTS:
      Crude incidence on-reserve was 31 per 100,000 persons per year (95% CI: 25 to
      37), twice as high as in the general population of BC (15.1 per 100,000). Higher
      incidence of hepatitis A was associated with more persons per housing unit and
      with presence of community water supply problems. CONCLUSIONS: An ecologic, multi
      factorial approach to disease prevention is needed, including upgrading housing
      and sanitary infrastructure, specific measures (i.e., hepatitis A vaccination)
      and general measures (e.g., education, poverty reduction, population planning).

PMID- 12790490
TI  - Voices from the wilderness: an interpretive study describing the role and
      practice of outpost nurses.
AB  - OBJECTIVE: Outpost nurses function as primary care providers and in a community
      health nursing role, providing comprehensive primary health care in Canada's
      underserved northern communities. Little information exists regarding how outpost
      nurses meet this expectation. The purpose of this interpretive study was to
      address the following research questions: 1) How do experienced outpost nurses
      perceive and enact their role? 2) How are practical knowledge and clinical wisdom
      revealed in the practice narratives of experienced outpost nurses? METHODS:
      Purposive sampling was used to recruit the nine experienced outpost nurses who
      participated by sharing narratives of clinical practice. Data analysis was
      conducted in accordance with Benner's model of interpretive phenomenology.
      Paradigm and exemplary cases served to ground the interpretation in the data.
      RESULTS: Four themes emerged from the data: a) primary care competencies are
      fundamental to outpost practice, b) nurses evolve into the outpost role by
      learning community health competencies and adapting to context-specific practice
      issues, c) experienced outpost nurses build and maintain responsive relationships
      with communities, and d) experienced outpost nurses become comfortable with the
      autonomy and responsibility of practice. DISCUSSION: The findings of this study
      reinforce the complex nature of outpost nursing; it is an anomalous community
      health nursing role grounded in primary care competency. Interpretation of the
      data suggests that outpost nurses share practice domains and competencies with
      nurse practitioners. A better understanding of the outpost nursing role clarifies
      how nurses might better contribute to improving the health status of northern
      residents, helping northern communities become healthy communities.

PMID- 12790491
TI  - The Canadian Institutes of Health Research, Institute of Aboriginal People's
      Health: a global model and national network for Aboriginal health research
      excellence.

PMID- 12790492
TI  - Public health in Canada: what are the real issues?

PMID- 12790493
TI  - University students immunized and not immunized for measles: a comparison of
      beliefs, attitudes, and perceived barriers and benefits.
AB  - OBJECTIVE: To compare students who were immunized or not immunized during the
      1997 Simon Fraser University measles outbreak in British Columbia. METHODS:
      Descriptive comparative study using the Health Belief Model as a theoretical
      framework. A self-administered questionnaire was mailed to a stratified random
      sample of 400 immunized and 400 non-immunized SFU students. RESULTS: Perceived
      susceptibility, severity, barriers, cues to action, threat and student age were
      significantly related to being immunized. Logistic regression analysis achieved
      an overall correct prediction rate of 84.7% by including the contribution of the
      four variables of susceptibility, barriers, cues to action, and health
      motivation. Content analysis of the non-immunized students' descriptions of what
      it would have taken for them to be immunized indicated the influence of these
      four variables. DISCUSSION: The Immunization Health Belief Model Scale is a
      valuable tool for ascertaining attitudes and beliefs relating to immunization
      decision-making. Interventions targeted to significant beliefs may increase
      immunization coverage levels and result in improved disease prevention.

PMID- 12790494
TI  - [Accessibility to methadone substitution treatment: the role of a low-threshold
      program].
AB  - OBJECTIVE: To evaluate the accessibility to a Montreal low-threshold methadone
      program (Relais-Methadone). This program is aimed at a marginalized population of
      heroin addicts who are injection drug users (IDU). METHOD: The data (n = 141
      clients) were collected during the first year of the program implementation with
      questionnaires administered by the programme workers. RESULTS: Analysis of the
      characteristics of the clients revealed that the program does reach the target
      population. The program's clientele is characterized by long-time and frequent
      heroin use, unstable lifestyles, and the presence of numerous behaviours that put
      them at high risk for HIV transmission. The retention of clients in the program
      is very high (88%) within the first 30 days. INTERPRETATION: These results
      demonstrate the importance and value of flexible intervention programs in
      reaching a marginalized clientele exposed to the HIV virus, who would not have
      access to regular programs characterized by restrictive selection criteria and
      limited availability.

PMID- 12790495
TI  - Public perception of alcohol policy issues relating directly or indirectly to
      privatization: results from a 1999 Ontario survey.
AB  - OBJECTIVE: The purpose of this study is to measure public opinion on alcohol
      policy issues relating to youth, litigation, outlet density, and government
      action. The authors comment on the implications of public opinion with regard to
      proposals for privatization of alcohol retailing in Ontario. METHOD: Using data
      from a 1999 provincial survey (n = 1,288), the authors examine the opinions of
      Ontario adults (male and female over the age of 18) on seven alcohol policy
      related items. In order to identify characteristics of persons tending to express
      certain opinions, the opinion items are cross-tabulated with sex, age, drinking
      pattern, marital status, and education. A scale is created to show the level and
      strength of aggregate support for alcohol controls. A logistic regression
      confirms associations between demographic characteristics and opinions. RESULTS:
      The majority expresses opinions favouring alcohol controls and disagreeing with
      privatization (73% of total sample against). However, differences of opinion are
      observed within groups, between groups, and between items. In particular, higher
      risk drinkers stand out for their dislike of most control measures. DISCUSSION:
      Taken as a whole, the results suggest that privatization of alcohol retailing in
      Ontario would run contrary to the wishes of the majority. Disapproval would
      probably be even stronger if more people realized there is often a connection
      between privatization and increased outlet density, relaxation of other controls,
      and less consideration for public health.

PMID- 12790496
TI  - Suicidal behaviours among adolescents in northern Nova Scotia.
AB  - OBJECTIVES: To estimate the 12-month prevalence of suicidal behaviours by gender
      and to investigate the gender-specific factors associated with suicidal
      behaviours and to describe health service utilization by suicidal adolescents.
      METHODS: This was a cross-sectional study. The baseline data of the Adolescent
      Health Study conducted in northern Nova Scotia were used. RESULTS: Female
      students were more likely to report suicidal behaviours than male students (p <
      0.005). There was no gender difference in injurious suicide attempts. Depression
      was the strongest risk factor for suicidal behaviours in the two genders (p <
      0.005). Female students who reported drug use and living in a non-intact family
      were at higher risk of suicide attempts. Low self-esteem was positively
      associated with suicidal ideation and suicide planning among male students.
      Suicidal girls were more likely to seek professional help for emotional
      disturbance than boys. Family doctors were the most frequently contacted
      professional by suicidal adolescents. CONCLUSIONS: Some factors associated with
      suicidal behaviours among adolescents may be gender specific. Suicidal behaviours
      have been considered a depressive symptom. Most suicidal students, however, had
      not contacted a health professional for an emotional problem in this population.
      This presents challenges for prevention of suicidal behaviours among adolescents.

PMID- 12790497
TI  - Secular trends in self-reported violent activity among Ontario students, 1983
      2001.
AB  - INTRODUCTION: This paper examines secular trends in violence among Ontario
      students between 1983 and 2001, and variation by sex. METHODS: Using data from
      the Ontario Student Drug Use Survey, we examined self-reports of assault, weapon
      carrying, and gang fighting based on 10 cross-sectional surveys from 1983 to
      2001. Respondents were derived from representative samples of Ontario students in
      grades 7, 9, 11, and 13 (OAC) who completed in-class anonymous self-administered
      surveys. Data were weighted to account for the complex survey design and analyzed
      using logit trend analyses. RESULTS: Short-term trends (1991-2001) showed
      assault, weapon carrying, and gang fighting have been on downward trajectories
      since the mid-1990s, reaching the lowest prevalence in 2001 among males and
      females. Long-term trends (1983-2001) among 11th-graders showed assault increased
      between 1985 and 1999, but declined in 2001. Gang fighting among males increased
      during the late 1980s and again during the mid-1990s, but declined between 1997
      and 2001. Gang fighting among females remained at a stable, low level.
      DISCUSSION: Future monitoring is necessary to understand whether the decline in
      self-reported violent behaviour among adolescents is robust.

PMID- 12790499
TI  - Socioeconomic status, sense of coherence and health in Canadian women.
AB  - OBJECTIVE: The purpose of this study was to explore the role of sense of
      coherence (SOC) in the relationship between household income and self-rated
      health among Canadian women. SOC is a global orientation that enables one to
      perceive events of the world as comprehensible, manageable, and meaningful.
      METHODS: A secondary data analysis was conducted using the National Population
      Health Survey 1994-95. Only women between the ages of 20 and 64 (n = 6748) were
      selected for this study. Data were analysed using multivariate path analyses.
      RESULTS: SOC is a psychosocial factor that intervenes in the income and health
      relationship. It did not function, however, as an interaction buffer to
      ameliorate the adverse effects of low income on health. CONCLUSION: This study
      lends support for public health interventions that target the socioeconomic
      conditions that influence health, and for strategies that foster the development
      of a strong SOC.

PMID- 12790498
TI  - [Why are some children incompletely vaccinated at the age of 2?].
AB  - OBJECTIVE: A survey was conducted in the Province of Quebec to document the
      factors associated with an incomplete immunization status among 2-year-old
      children. METHODS: Parents of 430 completely and 266 partially vaccinated
      children selected from the computerized vaccination register agreed to
      participate. RESULTS: The non-simultaneous administration of the 2nd MMR and 4th
      DPT-P-Hib at 18 months of age was responsible for 46% of incompleteness. The
      following characteristics were significantly associated with an incomplete
      immunization status: being a single parent, > or = 2 children in the family, an
      older age at first immunization (> or = 3 months), parent's preference for
      postponing the second vaccine when two injections are scheduled for the same
      visit, perception of lack of information about vaccination, and disagreement with
      immunization recommendations. CONCLUSION: One of the key points of this study is
      the impact of the non-simultaneous administration of the two vaccines at 18
      months. Factors such as being a single parent and older age at first immunization
      might be used to design an early intervention for children who are most likely to
      be incompletely immunized. Even if parents are favourable towards immunization,
      they need to be well informed about the associated risks and benefits.

PMID- 12790500
TI  - The impact of switching to polymerase chain reaction for the diagnosis of
      Chlamydia trachomatis infections in women.
AB  - BACKGROUND: We noted a marked increase in Chlamydia trachomatis (CT) infections
      in the Capital Health Region of NS coincident with substitution of a PCR for an
      enzyme immunoassay (EIA). We reviewed our experience to determine the cost of
      switching and the impact on the number of new infections diagnosed. METHODS:
      Information on the number of EIA and PCR tests performed on women was retrieved
      from an abstracted laboratory information database. We examined records of
      testing performed between April 1998 and December 2001. Prior to June 2001, all
      genital swabs were tested using the MicroTrak, II Chlamydia EIA and confirmed by
      direct fluorescence examination. After July 2001, genital swabs were tested using
      the COBAS AMPLICOR C. trachomatis test. RESULTS: During the study period, 62,288
      EIA tests were performed on specimens submitted; 2,061 (3.33%) were positive. In
      the six months when testing was performed by the PCR method, 9,559 PCR tests were
      performed, 463 (4.84%) were positive; 46% increase. In the three years before PCR
      testing was implemented, an average of 1,626 specimens were submitted monthly. An
      average of 54 tests were positive (3.3%). The cost for each positive detected by
      PCR was 208 dollars Cdn and 226 dollars by EIA. CONCLUSIONS: The switch to PCR
      for the diagnosis of CT produced a marked increase in the number of chlamydia
      infections diagnosed. The recent increase in the number of reported CT cases in
      Canada may be due in large part to more sensitive tests. Surprisingly, the cost
      of each positive test by PCR was 18 dollars Cdn less than that of the EIA.

PMID- 12790501
TI  - A descriptive analysis of two mobile crisis programs for clients with severe
      mental illness.
AB  - PURPOSE: To describe cases seen by two Mobile Crisis Programs (MCPs) for
      individuals with severe mental illnesses. Focus is on client characteristics,
      mental health status, interventions, referrals, and immediate outcomes. METHODS:
      Data were collected retrospectively through a chart review of clinical record
      forms and accompanying progress notes for cases seen by the MCPs over a one-year
      period. A total of 981 cases were included in the study. Data were analyzed using
      descriptive and bivariate statistics. RESULTS: Most cases involved clients who
      were female (60.2%), single (55.8%), living at home (56.8%), unemployed (85.6%),
      and between 20 and 44 years of age (44.5%). The two programs varied on a number
      of factors related to the demographic profile and mental health needs of the
      different geographical regions in which they are located. CONCLUSIONS: Findings
      highlight the need for further research into how MCPs can be integrated with
      related mental health services in offering clients the least intrusive and most
      efficient services.

PMID- 12790502
TI  - Absence of facial type differences among preschool children with sleep-related
      breathing disorder.
AB  - The aim of this study was to find out whether there are specific facial types and
      a specific hyoid bone position in preschool children with sleep-related breathing
      disorder (SBD). A total of 69 children were divided into 4 groups based on the
      mandibular line/Frankfurt horizontal angle and apnea index. There were 19
      children with hyperdivergent facial type and SBD and 19 children with neutral
      facial type and SBD, all of them with documented 0 < AI < 5. Ten children had
      hyperdivergent facial type and non-SBD, and 21 children neutral facial type and
      non-SBD. The present findings show that SBD may be associated with both
      hyperdivergent and neutral facial type. Furthermore, we could not find any
      specific hyoid bone position related to SBD, non-SBD, or to facial type. In
      conclusion, it is important to note that while evaluation based on facial type
      (mandibular shape or position) does not necessarily distinguish between children
      with SBD and children without SBD (non-SBD), important differences are found in
      the pharynx. Short nasal floor length, long soft palate, and particularly short
      upper pharyngeal width can be considered indicators of SBD.

PMID- 12790503
TI  - Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis
      imperfecta.
AB  - Two semiquantitative scoring systems, Clinical Radiographic Score (CRS) and
      Dysplastic Dentin Score (DDS), were introduced for analyzing degree of dysplastic
      manifestations in dentin. The utility of both systems was demonstrated in a large
      material of teeth from patients with dentinogenesis imperfecta (DI) and
      osteogenesis imperfecta (OI). Twenty teeth from healthy controls, 81 teeth from
      40 patients with OI, and 18 teeth with DI without OI (DI type II) were examined.
      The degree of dysplasia was correlated with type and form of OI and type of DI.
      The median DDS did not differ between DI associated with OI (DI type I) and DI
      type II. DDS in OI patients without clinical signs of DI was above that of
      control teeth. Both circumpulpal and mantle dentin showed increased DDS, although
      circumpulpal dentin was more severely affected. The median DDS was highest for
      the most severe type of non-lethal OI (type III). DDS increased significantly
      with form (severity) of OI. A significant association between DDS and CRS was
      found, although diagnosis of DI in less severe cases was not possible based on
      radiographic or clinical signs alone. Thus, the DDS system proved valuable when
      the CRS system based on radiographic/clinical manifestations failed, the most
      significant finding being subclinical histological manifestations of DI in
      patients with OI but without clinical or radiographic signs of DI. These subtle
      dysplastic changes are most likely an expression of genetic disturbances
      associated with OI and should not be diagnosed as DI, but rather be termed
      histologic manifestations of dysplastic dentin associated with OI.

PMID- 12790504
TI  - Perception of dental fluorosis amongst Ethiopian children and their mothers.
AB  - This study was conducted in three Ethiopian Rift Valley villages known for
      endemic fluorosis. Three-hundred-and-six adolescents (12-15 years) and 233
      mothers participated. The aim was to study dental fluorosis in the youngsters and
      to assess the extent of agreement between clinical and self-rated discoloration
      and pitting of teeth, and also the level at which dental fluorosis is perceived
      as a problem both by children and their mothers. The children (154 M and 152 F)
      gave a simple self-assessment of tooth-color and quality of their teeth, and were
      subsequently examined for dental fluorosis. Finally, four color photographs of
      teeth with dental fluorosis (TF-scores 2, 3, 5, and 7) were used as references
      during a structured oral interview of the children, as well as their mothers. At
      TF score > or = 2, the prevalence of dental fluorosis on maxillary central
      incisors was 72% and 37% at TF score > or = 4. The mean TF score was
      significantly higher among boys than among girls of unemployed fathers compared
      to children of employed fathers. The likelihood of reporting problems with dental
      appearance increased with increasing individual TF scores. The child/mother pairs
      found teeth with TF scores 2 and 3 esthetically acceptable, while teeth with TF
      scores 5 and 7 were considered unacceptable. Mothers were more critical of severe
      fluorosis than were their children.

PMID- 12790505
TI  - Flexural strength and modulus of a novel ceramic restorative cement intended for
      posterior restorations as determined by a three-point bending test.
AB  - The aim of this study was to compare a new restorative cement intended for
      posterior restorations, Doxadent, with other types of tooth-colored materials as
      regards flexural strength and flexural modulus. The new restorative material
      consists mainly of calcium aluminate. Four hybrid resin composites, one polyacid
      modified resin composite, one resin-modified glass ionomer cement, one
      conventional glass ionomer cement, one zinc phosphate cement, and an experimental
      version as well as the marketed version of Doxadent were investigated. Flexural
      strength and flexural modulus were tested according to ISO standard 4049 and
      determined after 1 d, 1 week, and 2 weeks. Together with the zinc phosphate
      cement, Doxadent had the lowest flexural strengths (13-22 MPa). The strongest
      materials were the resin composites and the polyacid-modified resin composite (83
      136 MPa). The highest flexural modulus was found for Doxadent (17-19 GPa). The
      flexural strength of Doxadent decreased significantly from 1 week to 2 weeks,
      while flexural modulus remained unchanged. The other materials reacted in
      different ways to prolonged water storage. It can be concluded that the
      restorative cement Doxadent had significantly lower flexural strength and
      significantly higher flexural modulus than today's materials used for direct
      posterior restorations.

PMID- 12790506
TI  - Effects of cognitive therapy, applied relaxation and nitrous oxide sedation. A
      five-year follow-up study of patients treated for dental fear.
AB  - Five years after completing a controlled, randomized treatment trial comparing
      the effect of nitrous oxide sedation (NO), cognitive therapy (CT), and applied
      relaxation (AR), all 62 patients who had participated were invited to a follow-up
      questionnaire study. Forty-three responded. All participants had been to the
      dentist during the follow-up period. Mean scores (s) on Corah's Dental Anxiety
      Scale (CDAS) and Symptom Checklist 90 Revised (SCL-90-R, a measure of general
      psychological distress) were 10.4 (4.1) and 0.35 (0.34), respectively. There were
      no between-group effects. Significant changes across the assessment phases (at
      enrollment, after treatment, and 5 years after) were found for both dental fear
      and general distress (CDAS: F = 137.8, P < 0.01; SCL-90-R: F = 12.5, P < 0.01).
      However, no significant changes between measures obtained after treatment and at
      follow-up emerged. Seven participants (3 from the NO group, 2 from the CT group,
      and 2 from the AR group) had CDAS scores above 14, indicating a recurrent or
      continual dental fear problem. The majority (81%) assessed the dental fear
      treatment received 5 years previously to have been useful for them. In
      conclusion, the favorable effects on dental fear and general psychological
      distress continued at 5-year follow-up for all treatment groups.

PMID- 12790507
TI  - Dental health behavior, gastroesophageal disorders and dietary habits among
      Norwegian recruits in 1990 and 1999.
AB  - A questionnaire was given to representative samples of Norwegian recruits in 1990
      and 1999 to explore dental health habits, history of gastroesophageal disorders
      and diet with possible relations to dental erosion. The samples were 792 (mean
      age 20.9 years) and 676 (mean age 21.6 years), respectively, and the
      corresponding responses were 62% and 100%. Minor differences in self-reported
      dental health habits and gastroesophageal disorders were found. The respondents'
      dentists had provided information about dental erosion for 8.2% of the
      respondents in 1990 versus 14.5% in 1999. There was an increase in the reported
      frequency of daily intake of juice from 17% to 24% (P = 0.006) and carbonated
      soft drink from 54% to 61% (P = 0.025) in the period 1990-99. The frequency of
      training activity showed minor changes, but in 1999 it was more common to drink
      during exercise (94% versus 74% in 1990, P < 0.001), and the majority drank
      water. Sixteen percent of recruits ate oranges daily in 1990; in 1999 this had
      dropped to 11% (P = 0.012). The corresponding proportion that ate apples daily
      had dropped from 17% to 8% in the period (P < 0.001). It is likely that lifestyle
      factors related to diet among young men have changed in the period 1990-99 in a
      direction that may increase the prevalence of dental erosions.

PMID- 12790508
TI  - Dental age and dental health determined longitudinally from patient records in
      three towns in Finland.
AB  - The aims of this study were to test the suitability of normal dental records in
      determining the eruption times of teeth and to compare the retrospective
      longitudinal DMF values with the statistical cross-sectional means. Patient
      records for two cohorts (1970 and 1980) were collected from three Finnish towns.
      The study population comprised 1910 children. The eruption times of the permanent
      teeth, DMFT and DMFS curves (excluding F due to fractures and M due to
      orthodontic reasons) were investigated for the year of examination in different
      study locations. The cross-sectional DMF values were compared to longitudinally
      calculated data. Tooth eruption was earlier in girls than in boys. However, girls
      did not have significantly higher DMF values than boys. In all towns, dental
      health was significantly better in the 1980 cohort than in the 1970 cohort.
      Comparison of the cross-sectional DMF values in the municipal health center
      statistics showed that the mean statistics gave considerably higher values than
      the measured values did after 15 years of age. The inconsistency between measured
      longitudinal DMF values and the cross-sectional statistical DMF values indicates
      the importance of creating computer programs for analyzing data longitudinally
      from normal dental records.

PMID- 12790509
TI  - Economic evaluation of a risk-based caries prevention program in preschool
      children.
AB  - We have previously reported that, in young children, a risk-based caries
      prevention program compared with conventional prevention has a good caries
      preventive effect. The present study aimed to assess the economic aspects of this
      program. We used the presence of mutans streptococci in plaque (Dentocult-SM)
      and/or the presence of incipient carious lesions at 2 years of age for risk
      assessment, and measured the outcome of caries (yes/no) at the age of 5 years.
      Dental assistants carried out the screening and preventive work. The economic
      analysis included the actual running costs of the program during the 3-year
      follow-up based on the time spent on dental visits. The costs per child per 3
      years were significantly lower in the risk-based group (54 euros) than in the
      conventional prevention group (69 euros) (Student's t test, P = 0.004). If a
      dentist with an assistant had done all the work, the costs would have been twice
      as high. Compared to conventional prevention, the results suggest that risk-based
      prevention can be effective in reducing both costs and dental caries in preschool
      children, provided that the screening and preventive measures are delegated to
      preventive dental assistants.

PMID- 12790510
TI  - Subgingival microbiota levels and their associations with periodontal status at
      the sampled sites in an adult Sudanese population using miswak or toothbrush
      regularly.
AB  - Little information is available on the effect of miswak use on gingival
      microbiota. We assessed levels of 28 oral bacteria in subgingival plaque of adult
      Sudanese miswak (n = 38) and toothbrush users (n = 36) age range 20-53 years
      (mean 34.6 years) to study associations between these bacteria, oral hygiene
      method, and periodontal status at the sampled sites. A pooled subgingival plaque
      sample from 6 probing sites of 1 selected tooth in each jaw was obtained from
      each subject. Whole genomic DNA probes and the checkerboard DNA-DNA hybridization
      were used in assessing 74 pooled samples. Using 10(5) bacterial cells threshold,
      between 2.6% and 47.4% of miswak users and between 2.8% and 36.1% of toothbrush
      users harbored the investigated species. The percentages of subjects with the
      investigated species at 10(6) bacterial cells varied between 2.6% and 39.5% in
      miswak and between 2.8% and 36.1% in toothbrush users. Miswak users harbored
      significantly higher Streptococcus intermedius, Actinobacillus
      actinomycetemcomitans, Veillonella parvula, Actinomyces israelii, and
      Capnocytophaga gingivalis, and significantly lower Selenomonas sputigena,
      Streptococcus salivarius, Actinomyces naeslundii, and Streptococcus oralis than
      did toothbrush users. Probing pocket depth > or = 6 mm showed significantly (P <
      0.05) higher levels of Porphyromonas gingivalis, Treponema denticola, Bacteroides
      forsythus, Fusobacterium nucleatum, and V. parvula than those 4-5 mm. Our results
      indicate that the type of oral hygiene had a significant effect on levels of 11
      out of 28 bacterial species, and that the type of effect was also dependent on
      type of bacteria and probing pocket depth.

PMID- 12790511
TI  - Occlusal status in orthodontically treated and untreated adolescents.
AB  - In order to evaluate the outcome of orthodontic care, all available 16-year-old
      adolescents (n = 138) living within the catchment area of one Finnish health
      center were invited for a clinical examination. A total of 126 adolescents
      participated, corresponding to 79% of the whole age cohort. Of these, 47% had
      been treated orthodontically, 2% were still wearing appliances, and 51% were
      untreated. In 80% of cases, a non-extraction treatment was carried out. All
      occlusions were evaluated using a recently developed occlusal morphology and
      functional index (OMFI) based on assessment of 6 morphological and 4 functional
      traits which are classified applying an acceptable-non-acceptable dichotomy. The
      occlusal status in untreated individuals was used as a second reference in
      comparisons between the treated and untreated occlusions. The morphological
      criteria for an acceptable occlusion were met by 42% of the participants and the
      functional criteria by 64%. Although the treated occlusions failed to meet the
      criteria of morphological acceptability more often than the untreated ones (73%
      vs 40%), the proportions of non-acceptable occlusions were fairly high among
      untreated occlusions. The main reasons for non-acceptability were the failure of
      the canine relationship, overbite, and protrusion movement to fulfill the
      criteria of acceptability. Only 19% of the adolescents had occlusions classified
      as acceptable, both morphologically and functionally. In the evaluated health
      center, the allocation of resources resulted in a high coverage of orthodontic
      care. However, our results indicate that the general occlusal status in the
      examined age cohort did not reach an optimal level.

PMID- 12790512
TI  - Hepatitis C virus therapies: current treatments, targets and future perspectives.
AB  - Chronic hepatitis C virus (HCV) infection is the cause of an emerging global
      epidemic of chronic liver disease. Current combination therapies are at best 80%
      efficacious and are often poorly tolerated. Strategies to improve the therapeutic
      response include the development of novel interferons, nucleoside analogues with
      reduced haemolysis compared with ribavirin and inosine 5'-monophosphate
      dehydrogenase inhibitors. Compounds in preclinical or early clinical trials
      include small molecules that inhibit virus-specific enzymes (such as the serine
      proteases, RNA polymerase and helicase) or interfere with translation (including
      anti-sense molecules, iRNA and ribozymes). Advances in understanding HCV
      replication, obtaining a sub-genomic replicon and contriving potential small
      animal models, in addition to solving crystallographic structures for the
      replication enzymes, have improved prospects for developing novel therapies. This
      review summarizes current and evolving treatments for chronic hepatitis C
      infection. In addition, progress in HCV targets and drug discovery tools valuable
      in the search for novel anti-HCV agents is detailed.

PMID- 12790513
TI  - Ribavirin derivatives with a hexitol moiety: synthesis and antiviral evaluation.
AB  - Current standard therapy for the treatment of chronic infections with hepatitis C
      virus consists of combination therapy with (pegylated) interferon-alpha and
      ribavirin. 1,5-Anhydrohexitol nucleoside analogues are constrained congeners
      known to mimic the ribonucleoside conformation. Within this series some analogues
      are endowed with strong antiviral properties, particularly against herpesviruses.
      The six-membered anhydrohexitol ring was, therefore, combined with the triazolyl
      carboxamide moiety of ribavirin, thus providing a new series of ribavirin
      analogues. None of the newly synthesized compounds elicited any substantial
      antiviral activity, neither against herpes simplex virus type 1 and 2, nor
      against bovine viral diarrhoea virus (a surrogate for hepatitis C virus) or the
      yellow fever virus.

PMID- 12790514
TI  - Synthesis and antiviral activity of a series of new cyclohexenyl nucleosides.
AB  - A series of new cyclohexenyl nucleosides is synthesized by coupling the
      heterocyclic bases with a protected cyclohexenyl precursor under Mitsunobu
      conditions. The compounds were evaluated for their antiviral and cytostatic
      activity. Pronounced activity against herpes simplex virus type 1 and type 2 was
      observed for the 2,6-diaminopurine analogue.

PMID- 12790515
TI  - Cellular pharmacology of D-d4FC, a nucleoside analogue active against drug
      resistant HIV.
AB  - The backbone of effective highly active antiretroviral therapy regimens for the
      treatment of HIV infections currently contains at least two nucleosides. Among
      the features that influence the potency of each component of a regimen and the
      overall efficacy of the combination are the cellular uptake and bioconversion of
      nucleoside analogues to their active triphosphate form, and the extent of
      possible interactions in these steps that might occur when more than one
      nucleoside is used in a regimen. D-d4FC (Reverset), a new cytidine analogue with
      the ability to inhibit many nucleoside-resistant viral variants, was examined for
      these parameters. In phytohemaglutinin-stimulated human peripheral blood
      mononuclear cells, D-d4FC was taken up in a rapid (8 h to 50% maximal value),
      saturable (plateau above 10 microM parent nucleoside concentration) process,
      resulting in levels of D-d4FC triphosphate that should provide potent antiviral
      activity against a variety of virus genotypes. Based on measurement of antiviral
      effects in cell culture, additive and in some cases, synergistic interactions
      were observed with protease inhibitors, non-nucleoside reverse transcriptase
      inhibitors or other nucleosides, including cytidine analogues.

PMID- 12790516
TI  - HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor
      beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (Reverset).
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) represent the cornerstone of
      highly active antiretroviral therapy when combined with non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) or HIV-1 protease inhibitors (PIs). Unlike the
      NNRTIs and PIs, NRTIs must be successively phosphorylated by cellular kinases to
      a triphosphate form, which represents the active metabolite possessing antiviral
      activity. Emergence of viral resistance to NRTIs has severely hampered treatment
      options for persons infected with HIV-1. As such, there is an urgent need to
      develop NRTIs capable of suppressing NRTI-resistant strains of HIV-1. We have
      recently reported that the cytidine analogue D-d4FC (DPC817, Reverset)
      effectively inhibits clinically prevalent resistant strains of HIV-1. In this
      report, we have extended these findings and now describe a detailed resistance
      profile for this novel NRTI. By examining a panel of 50 viruses carrying RTs
      derived from HIV-1 clinical isolates displaying a wide range of NRTI resistance
      mutations, we report that the median fold increase in effective antiviral
      concentration for such a panel of viruses is 3.2, which is comparable to
      tenofovir (2.8-fold) and didanosine (2.4-fold). D-d4FC is highly effective at
      inhibiting subsets of lamivudine- and zidovudine-resistant variants but, like
      other NRTIs, seems less potent against multi-NRTI-resistant viruses, particularly
      those carrying the Q151M complex of mutations. Finally, in vitro selections for
      HIV-1 mutants capable of replicating in the presence of D-d4FC yielded a mutant
      carrying the RT K65R mutation. This mutation confers 5.3- to 8.7-fold resistance
      to D-d4FC in vitro. These findings suggest that D-d4FC may represent an
      alternative NRTI for the treatment of individuals infected with lamivudine- and
      zidovudine-resistant strains of HIV-1.

PMID- 12790517
TI  - 2'-O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] modified oligonucleotides: symbiosis
      of charge interaction factors and stereoelectronic effects.
AB  - [structure: see text] Oligonucleotides with a novel, 2'-O-[2-[2-(N,N
      dimethylamino)ethoxy]ethyl] (2'-O-DMAEOE) modification have been synthesized.
      This modification, a cationic analogue of the 2'-O-(2-methoxyethyl) (2'-O-MOE)
      modification, exhibits high binding affinity to target RNA (but not to DNA) and
      exceptional resistance to nuclease degradation. Analysis of the crystal structure
      of a self-complementary oligonucleotide containing a single 2'-O-DMAEOE
      modification explains the importance of charge factors and gauche effects on the
      observed antisense properties. 2'-O-DMAEOE modified oligonucleotides are ideal
      candidates for antisense drugs.

PMID- 12790518
TI  - Organoplatinum(II) complexes as a color biomarker in solid-phase peptide
      chemistry and screening.
AB  - [reaction: see text] A novel organoplatinum(II) biomarker is introduced to
      facilitate the solid-phase screening of combinatorial libraries for substrates
      and inhibitors of enzymes and receptors. The robust organoplatinum(II) biomarker
      can be incorporated, on amine functions, in peptides using standard peptide
      coupling techniques. The chemistry, stability, and (reversible) coloration
      process with KI(3) of the organoplatinum(II) biomarker was investigated.

PMID- 12790519
TI  - A supramolecular "ship in bottle" strategy for enantiomeric selectivity in
      geminate radical pair recombination.
AB  - [reaction: see text] Reactions in which zeolites are modified with chiral
      inductors to serve as media for chiral induction are often limited by the
      propensity of both substrate and inductor to occupy the same supercage. Herein,
      we report a "ship in bottle" strategy utilizing the thermal decomposition of
      dioxetanes obtained from oxazolidinone-substituted enecarbamates for the
      enantioselective generation of methyl desoxybenzoin (MDB). Photoexcitation of the
      supramolecular geminate molecular pair results in enrichment of the opposite
      enantiomer of MDB.

PMID- 12790520
TI  - Determination of inorganic phosphate in serum and saliva using a synthetic
      receptor.
AB  - [structure: see text] A C(3)(v) symmetric synthetic receptor (1) was employed in
      an indicator-displacement assay to determine the phosphate concentrations in both
      horse serum and human saliva at biological pH. The determination of the phosphate
      concentrations in the serum and saliva using the colorimetric assay were 1.6 and
      5.1 mM, respectively. These results further accentuate the usefulness of
      synthetic receptors in truly practical applications.

PMID- 12790522
TI  - New and efficient procedure for the preparation of unsymmetrical silaketals.
AB  - [reaction: see text] A new and efficient procedure for the preparation of
      unsymmetrical silaketals via a three-step protocol without isolation of the
      intermediates is presented. The unsymmetrical silyl ethers and silanes can also
      be readily obtained via this sequence of reactions.

PMID- 12790521
TI  - Synthesis and characterization of an N-acylsulfonamide inhibitor of human
      asparagine synthetase.
AB  - [structure: see text] The synthesis of N-acylsulfonamide 6, which is an analogue
      of beta-aspartyl-AMP, is described. This compound appears to be the first and
      only potent inhibitor of human asparagine synthetase that has been described to
      date. The N-acylsulfonamide 6 exhibits slow-onset inhibition kinetics, with a
      K(i) of 728 nM. Preparation and characterization of two additional N
      acylsulfonamide analogues has also demonstrated the importance of hydrogen
      bonding interactions in the recognition of the AS inhibitor with the enzyme.
      These observations provide the basis for the discovery of new compounds with
      application in the treatment of drug-resistant leukemia.

PMID- 12790523
TI  - Utility of neodymium diiodide as a reductant in ketone coupling reactions.
AB  - [reaction: see text] The viability of NdI(2) as a one-electron reducing agent in
      organic synthesis has been examined by studying coupling reactions between alkyl
      chlorides and ketones and aldehydes.

PMID- 12790524
TI  - Synthesis of pyrroles through coupling of enyne-hydrazones with Fischer carbene
      complexes.
AB  - [reaction: see text] The coupling of enyne-imines with Fischer carbene complexes
      leads to the formation of alkenylpyrrole derivatives. Maximum yields of pyrrole
      adducts were obtained using N,N-dimethylhydrazones. A mechanism involving alkyne
      insertion followed by nucleophilic attack of the imine nitrogen at the
      intermediate alkenylcarbene complex was proposed.

PMID- 12790525
TI  - Benzaldehyde lyase-catalyzed enantioselective carboligation of aromatic aldehydes
      with mono- and dimethoxy acetaldehyde.
AB  - [reaction: see text] Benzaldehyde lyase from the Pseudomonas fluorescens
      catalyzes the reaction of aromatic aldehydes with methoxy and dimethoxy
      acetaldehyde and furnishes (R)-2-hydroxy-3-methoxy-1-arylpropan-1-one and (R)-2
      hydroxy-3,3-dimethoxy-1-arylpropan-1-one in high yields and enantiomeric excess
      via acyloin linkage. Aromatic aldehydes and benzoins are converted into enamine
      carbanion-like intermediates prior to carboligation.

PMID- 12790526
TI  - Synthesis and metal-binding properties of chelating fluorescein derivatives.
AB  - [reaction: see text] Two routes to highly functionalized metal-chelating
      fluorescein derivatives have been pursued. Compound 3 is partially quenched by a
      variety of first-row transition metal ions in aqueous solution, with EC(50)
      values ranging from 0.4 to 60 microM. Compounds of this type may find application
      in biological sensing.

PMID- 12790527
TI  - Lewis acid-induced intramolecular Friedel-Crafts cyclization of 1,3-bis-exocyclic
      dienes. a new route to 4a-methyltetrahydrofluorenes.
AB  - [reaction: see text] An efficient new method for constructing the 4a
      methyltetrahydrofluorene skeleton was achieved via Friedel-Crafts intramolecular
      cyclization of 1,3-bis-exocyclic dienes. This strategy offers a simple and
      promising method for accessing complex structures.

PMID- 12790528
TI  - Practical asymmetric synthesis of beta-trichloromethyl-beta-hydroxy ketones by
      the reaction of chloral or chloral hydrate with chiral imines.
AB  - [reaction: see text] Chloral or its hydrate undergoes the carbon-carbon bond
      formation reaction with various optically active imines in the absence of any
      additive, followed by hydrolysis, to produce the corresponding beta
      trichloromethyl-beta-hydroxy ketones in good yields with high
      enantioselectivities. In addition, the products with higher ee values were
      obtained by a simple recrystallization process.

PMID- 12790529
TI  - Oxidative 5-endo cyclization of enamides mediated by ceric ammonium nitrate.
AB  - [reaction: see text] Ceric ammonium nitrate mediates the oxidative 5-endo radical
      polar crossover reactions of beta-enamide esters to give 5,5-C,O-disubstituted
      gamma-lactams. Trapping of the intermediate cations leads to 5-hydroxy- or 5
      alkoxy-gamma-lactams depending upon the reaction conditions. The methodology was
      used to synthesize the basic heterocyclic ring fragments of the natural products
      L-755,807, Quinolacticin C, and PI-091.

PMID- 12790530
TI  - 2,6-Diamino-5,8-diaza-7,9-dicarba-purine.
AB  - [reaction: see text] The title compound, a constitutional isomer of the natural
      nucleobase 2,6-diaminopurine, undergoes regioselective electrophilic
      substitutions at carbon C-9.

PMID- 12790531
TI  - C-Nucleosidations with 2,6-diamino-5,8-diaza-7,9-dicarba-purine.
AB  - [structure: see text] Endocyclic iminium ions derived from l-4-amino-threose
      derivatives smoothly react with 2,6-diamino-5,8-diaza-7,9-dicarba-purine to give
      corresponding C(9)-nucleosides in high yields.

PMID- 12790532
TI  - Structure reinvestigation of gelsemoxonine, a constituent of Gelsemium elegans,
      reveals a novel, azetidine-containing indole alkaloid.
AB  - [structure: see text] The structure of gelsemoxonine, isolated from Gelsemium
      elegans Benth., was revised to be a novel oxindole alkaloid having an azetidine
      unit. A new alkaloid, 14,15-dihydroxygelsenicine, which was presumed to be a
      biosynthetic precursor of gelsemoxonine, was also isolated.

PMID- 12790533
TI  - Metal-dependent regioselective oxidative coupling of 5,10,15-triarylporphyrins
      with DDQ-Sc(OTf)3 and formation of an oxo-quinoidal porphyrin.
AB  - [reaction: see text] Regioselectivity of the oxidative coupling of 5,10,15
      triarylporphyrin metal complexes with DDQ-Sc(OTf)(3) was dependent on the central
      metal and meso-aryl substituent. Oxo-quinoidal porphyrin was obtained from Ni(II)
      porphyrin under the same conditions.

PMID- 12790534
TI  - New fluorescent photoinduced electron transfer chemosensor for the recognition of
      H2PO4-.
AB  - [structure: see text] The fluorescent chemosensor 1 bearing two imidazolium
      groups at the 1,8-position of anthracene has been designed for the recognition of
      anions through the (C-H)(+)- - -X(-) hydrogen bond formation. As unique tweezer
      like binding of 1 with anions is predicted by the ab initio calculations, strong
      anion-binding properties of chemosensor 1 are demonstrated by using fluorescence
      as well as (1)H NMR.

PMID- 12790535
TI  - Stereoselectivity of superacid-catalyzed Pictet-Spengler cyclization reactions.
AB  - [reaction: see text] High stereoselectivities were found in a wide range of
      superacid-catalyzed Pictet-Spengler cyclization reactions. Particularly in the
      cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity
      was observed under the superacid conditions as compared with the corresponding
      weak acid (TFA)-catalyzed (monocationic) cyclization reaction of the N
      benzylidene-2-(3',4'-dimethoxy)phenethylamines that bear electron-donating groups
      on the cyclizing aromatic ring. The computational study also supported the
      energetic favorability of the cyclization of the N,N-diprotonated imine and
      revealed a significantly early transition-state structure.

PMID- 12790536
TI  - Parallel approach to selective catalysts for palladium-catalyzed desymmetrization
      of 2,4-cyclopentenediol.
AB  - [reaction: see text] Work toward the development of a bis-phosphine ligand system
      for the palladium-catalyzed desymmetrization of meso-diols is reported. A
      parallel approach using phosphine-containing amino acids and a "representational
      search" was taken to find a polymer-supported catalyst system. The selectivities
      reported are comparable to many other polymer-bound asymmetric catalysts.

PMID- 12790537
TI  - Synthetic studies on ecteinascidin-743: constructing a versatile pentacyclic
      intermediate for the synthesis of ecteinascidins and saframycins.
AB  - [reaction: see text] The asymmetric synthesis of a highly functionalized
      pentacyclic tetrahydroisoquinoline relevant to the ecteinascidin, saframycin,
      safracin, and renieramycin family of antitumor alkaloids is described.

PMID- 12790538
TI  - Limits of delocalization in through-conjugated dinitrenes: aromatization or bond
      formation?
AB  - [reaction: see text] Dinitrenes 4 and 5 both can form quinonoidal structures by
      conjugative bond formation. However, ESR spectroscopy detects a thermally
      populated, excited-state, triplet quinonoidal structure only for 4, with a zero
      field splitting of |D/hc| = 0.0822 cm(-)(1), |E/hc| congruent with 0.0 cm(-)(1).
      The tendency to maintain aromaticity in the additional ring of 5 favors a
      dinitrene structure (with one less formal pi-bond) over a quinonoidal structure.
      The thermally populated quintet state of 5 has a zero-field splitting of |D/hc| =
      0.287 cm(-)(1), |E/hc| <or= 0.002 cm(-)(1).

PMID- 12790539
TI  - Asymmetric transfer hydrogenation of prochiral ketones in aqueous media with new
      water-soluble chiral vicinal diamine as ligand.
AB  - [reaction: see text] An easily accessible water-soluble chiral o-sulfonated 1,2
      diphenylethlenediamine 2 and its mono-N-tosylated derivative 3 were synthesized
      for the first time. The ruthenium-complex-catalyzed reduction of prochiral
      ketones in aqueous media has been examined by using 3 as ligand and sodium
      formate as the source of hydrogen. The asymmetric transfer hydrogenation of omega
      bromo acetophenones was achieved, in which only formate displacement occurred
      when formic acid/triethylamine azeotrope was used as the hydrogen donor.

PMID- 12790540
TI  - Efficient synthesis of enantiopure beta-amino-gamma-keto acids from l-homoserine.
AB  - [reaction: see text] A variety of beta-amino-gamma-keto acids were prepared in
      four steps from commercially available l-homoserine. The reaction sequence is
      highlighted by a Ni-catalyzed Grignard addition to a N-protected derivative of l
      homoserine. One of the beta-amino-gamma-keto acids was then used to create a beta
      peptide trimer composed solely of beta-amino-gamma-keto acids.

PMID- 12790541
TI  - Highly stereoselective anti SN2' substitutions of (Z)-allylic
      pentafluorobenzoates with polyfunctionalized zinc-copper reagents.
AB  - [reaction: see text] Allylic substitution reactions of zinc-copper
      organometallics on (Z)-allylic pentafluorobenzoates proceed with very high
      regioselectivity and excellent anti selectivity. The high fidelity in transfer of
      stereochemical information allowed a short synthesis of (+)-ibuprofen (97% ee).

PMID- 12790542
TI  - Tentoxin as a scaffold for drug discovery. Total solid-phase synthesis of
      tentoxin and a library of analogues.
AB  - [reaction: see text] A solid-phase method for the synthesis of tentoxin has been
      developed. Two key steps-dehydration and N-alkylation-are carried out while the
      peptide is anchored to the resin. The method, which has been validated by the
      preparation of a library of tentoxin analogues, should be applicable to the
      generation of further libraries that have the tentoxin scaffold structure, as
      well as other structures containing N-alkylated didehydroamino acids.

PMID- 12790543
TI  - Bhc-diol as a photolabile protecting group for aldehydes and ketones.
AB  - [reaction: see text] 6-Bromo-4-(1,2-dihydroxyethyl)-7-hydroxycoumarin (Bhc-diol)
      can be used under simulated physiological conditions as a photoremovable
      protecting group for aldehydes and ketones. The single- and two-photon-induced
      release of benzaldehyde, piperonal, acetophenone, and cyclohexanone is
      demonstrated.

PMID- 12790544
TI  - Biomimetic synthesis of fused polypyrans: oxacyclization stereo- and
      regioselectivity is a function of the nucleophile.
AB  - [reaction: see text] The stereoselectivity of Lewis acid-induced endo
      regioselective oxacyclizations of 1,4-diepoxides is dependent upon the nature of
      the terminating nucleophile. For instance, the tert-butyl carbonate-substituted
      diepoxide of 3,6-dimethylhepta-2,5-dien-1-ol provides a cis-fused bicyclic
      product, whereas the N,N-dimethylcarbamate derivative affords the trans-fused
      diastereomer. Stereospecific and regioselective conversion of the tertiary
      carbamate-terminated 1,4,7-triepoxide (I) to tricyclic all-trans-fused polypyran
      (II) is also demonstrated.

PMID- 12790545
TI  - Photochromic radical compounds based on a naphthopyran system.
AB  - [reaction: see text] Naphthopyran derivatives with aminoxyl substituents (4a,b)
      gave the corresponding open-formed isomers (5a,b) by irradiation, which could be
      changed back to the starting closed-formed naphthopyrans by the treatment with
      SiO(2) as a catalyst. The tuning of intermolecular magnetic interactions between
      the isomer couples was found to be possible in these reversible systems.

PMID- 12790546
TI  - Microwave-assisted C-H bond activation: a rapid entry into functionalized
      heterocycles.
AB  - [reaction: see text] Microwave irradiation strongly accelerates the rhodium
      catalyzed intramolecular coupling of a benzimidazole C-H bond to pendant alkenes.
      The cyclic products were formed in moderate to excellent yields with reaction
      times less than 20 min. Additionally, the use of microwave irradiation allowed
      the reactions to be performed without any solvent purification and with minimal
      precautions to exclude air.

PMID- 12790547
TI  - Diels-Alder reactions of perfluorobicyclo[2.2.0]hex-1(4)-ene with aromatics.
AB  - [reaction: see text] The title perfluoroalkene cycloadds to a variety of aromatic
      hydrocarbons, including benzene. It is the first alkene to yield a Diels-Alder
      adduct with benzene and is thus among the most potent dienophiles known.

PMID- 12790548
TI  - Titanium-mediated [2 + 2 + 2] coupling of diynes with homoallylic alcohols.
AB  - [reaction: see text] In connection with the known diyne-ene [2 + 2 + 2]
      cycloaddition reactions mediated by titanium aryloxides, the ability of titanium
      alkoxides to promote coupling of a titanacyclopentadiene with an alkene has been
      assessed for the isomerization-free preparation of 1,3-cyclohexadienes. The
      successful cycloaddition by titanium alkoxides is predicated on the use of
      homoallylic alcohols as the olefin component. With secondary homoallylic
      alcohols, high 1,3-diastereoselectivity is observed, which lends itself to
      enantioselective preparation of functionalized 1,3-cyclohexadienes.

PMID- 12790549
TI  - A general, Bronsted acid-catalyzed hetero-Michael addition of nitrogen, oxygen,
      and sulfur nucleophiles.
AB  - [reaction: see text] Strong Bronsted acids such as
      bis(trifluoromethanesulfon)imide catalyze the hetero-Michael addition of
      carbamates, alcohols, and thiols to alpha,beta-unsaturated ketones, alkylidene
      malonates, and acrylimides. Scope, reaction rates, and yields are superior to
      comparable Lewis acid-catalyzed processes.

PMID- 12790550
TI  - Asymmetric synthesis of allyl- and alpha-allenylamines from chiral imines and
      alkynes via (eta(2)-imine)Ti(O-i-Pr)2 complexes.
AB  - [reaction: see text] The reaction of a divalent titanium reagent Ti(O-i-Pr)(4)/2i
      PrMgX with optically active arylaldimines derived from arylaldehydes and O
      methylphenylglycinol provided, in a highly diastereoselective manner, chiral
      (eta(2)-imine)Ti(O-i-Pr)(2) complexes, which in turn reacted with 1-alkynes or
      propargyl compounds to give optically active allyl- and alpha-allenylamines,
      respectively.

PMID- 12790552
TI  - Stereoselective synthesis of functionalized pyrrolidines by ruthenium porphyrin
      catalyzed decomposition of alpha-diazo esters and cascade azomethine ylide
      formation/1,3-dipolar cycloaddition reactions.
AB  - [reaction: see text] Ruthenium porphyrins catalyze three-component coupling
      reaction of alpha-diazo esters with a series of N-benzylidene imines and alkenes
      to form functionalized pyrrolidines in excellent diastereoselectivities. The
      reaction proceeds via a reactive ruthenium-carbene intermediate and its
      subsequent reaction with imine to generate azomethine ylide, which reacts with
      alkenes via 1,3-diploar cycloaddition.

PMID- 12790551
TI  - Stereochemical diversity through cyclodimerization: synthesis of polyketide-like
      macrodiolides.
AB  - [reaction: see text] An expeditious procedure for the direct formation of
      stereochemically well-defined macrodiolides is described. Cyclodimerizations of
      enantioenriched C7 and C8 hydroxy esters 6 in the presence of catalytic amounts
      of distannoxane transesterification catalysts afford 14- to 22-membered
      macrodiolides 7-9 bearing up to six stereocenters. Additional structural
      diversity is introduced by further stereoselective reactions on selected
      macrodiolides 7a, 7g, 10a, and 11.

PMID- 12790553
TI  - Novel lactonization with phenonium ion participation induced by hypervalent
      iodine reagents.
AB  - [reaction: see text] A novel lactonization of 4-aryl-4-pentenoic acids is
      described using aryl-lambda(3)-iodanes as reagents for this transformation. The
      hypervalent iodine species acts as a hypernucleofuge, generating intermediate
      phenonium ions, which react to aryl-migrated lactones.

PMID- 12790554
TI  - Palladium-catalyzed rearrangement/arylation of 2-allyloxypyridine leading to the
      synthesis of N-substituted 2-pyridones.
AB  - [reaction: see text] The Pd-catalyzed one-pot rearrangement/arylation of 2
      allyloxypyridine is described. The catalyst/base combination of Pd[P(t
      Bu)(3)](2)/Ag(2)CO(3) was found to be optimal for this one-pot
      rearrangement/arylation. The initial rearrangement of 2-allyloxypyridine was
      found to be catalyzed by both Pd(0) and Pd(II) complexes with different
      mechanisms.

PMID- 12790555
TI  - m-Phenylene-linked aromatic poly(aminium cationic radical)s: persistent high-spin
      organic polyradicals.
AB  - [structure: see text] High molecular weight and networked aromatic polyamines
      prepared by palladium-catalyzed polycondensation were oxidized to yield the
      corresponding poly(aminium cationic radical)s, which displayed a substantial
      stability and an intramolecular ferromagnetic interaction of eight or nine spins.

PMID- 12790556
TI  - Microwave-assisted synthesis of diaryl ethers without catalyst.
AB  - [reaction: see text] Diaryl ethers have been prepared by direct coupling of
      phenols including those that bear a strong electron-attracting substituent to
      electron-deficient aryl halides through S(N)Ar-based addition reactions with
      assistance of microwave irradiation in high to excellent yields within 5-10 min.
      No catalysts were required under our conditions.

PMID- 12790558
TI  - Asymmetric allylation of unsymmetrical 1,3-diketones using a BINAP-palladium
      catalyst.
AB  - [reaction: see text] The chiral palladium complex generated in situ from
      [Pd(eta(3)-allyl)Cl](2) and (R)-BINAP is a good catalyst for the catalytic
      asymmetric allylation of 1,3-diketones. The reaction provided chiral 2,2-dialkyl
      1,3-diketones with 64-89% ee in high yields (13 examples). Enantiomeric excesses
      are strongly affected by the gamma-substituent of the allylic substrates. A
      variety of unsymmetrical 1,3-diketones were alkylated with cinnamyl acetate in
      good enantioselectivities via use of the BINAP-palladium catalyst (77-89% ee).

PMID- 12790557
TI  - New stereoselective beta-C-glycosidation by uncatalyzed 1,4-addition of
      organolithium reagents to a glycal-derived vinyl oxirane.
AB  - [reaction: see text] Epoxide 4 is generated in situ from d-glucal-derived hydroxy
      mesylate 3. Reaction of epoxide 4 with a series of alkyl- and aryllithium
      reagents affords 2,3-unsaturated beta-C-glycosides with excellent 1,4
      regioselectivity and complete stereoselectivity for the beta-glycoside. Other
      organometallic reagents demonstrate more complex behavior in their reactions with
      epoxide 4.

PMID- 12790559
TI  - New strategy for the synthesis of tetrahydroisoquinoline alkaloids.
AB  - [reaction: see text] A general strategy for the formation of 1,3-cis-substituted
      tetrahydroisoquinolines is described from ortho-iodo imines involving Larock
      isoquinoline synthesis, addition of organolithium compounds to unactivated
      isoquinolines, and ionic hydrogenation. In addition, a new synthesis of lactams
      via an unprecedented azide cyclization in the presence of a sulfonium ion is
      described.

PMID- 12790560
TI  - Synthesis of ethyl 3-aryl-1-methyl-8-oxo- 8H-anthra[9,1-gh]quinoline-2
      carboxylates as dyes for potential application in liquid crystal displays.
AB  - [reaction: see text] Two new fluorescent ethyl 3-aryl-1-methyl-8-oxo-8H
      anthra[9,1-gh]quinoline-2-carboxylates have been synthesized for the first time
      by cyclization of 3-(arylidene-amino)-benzo[de]anthracen-7-ones with 3-oxo
      butyric acid ethyl ester. The cyclization reaction was investigated with and
      without concentrated hydrochloric acid as a catalyst. New dyes have shown a very
      good orientation parameter (S(A)) in nematic liquid crystal, indicating a high
      potential for application in liquid crystal displays.

PMID- 12790561
TI  - The 4,6-O-[alpha-(2-(2- iodophenyl)ethylthiocarbonyl)benzylidene] protecting
      group: stereoselective glycosylation, reductive radical fragmentation, and
      synthesis of beta-D-rhamnopyranosides and other deoxy sugars.
AB  - [reaction: see text] In the thioglycoside/BSP/Tf(2)O glycosylation method, the
      4,6-O-[alpha-(2-(2-iodophenyl)ethylthiocarbonyl)benzylidene] group enforces beta
      selectivity in mannopyranosylations. Following glycosylation, treatment with
      Bu(3)SnH in toluene at reflux affords regioselective, reductive fragmentation to
      the 6-deoxy-beta-mannosides (beta-rhamnosides). Applied to glucosides, the
      radical fragmentation provides 6-deoxyglucosides, whereas 4-deoxygalactosides are
      the preferred products in the galactose series. The radical fragmentation is
      fully compatible with the presence of benzyl and p-methoxybenzyl ethers and with
      acetate esters

PMID- 12790563
TI  - Stereochemical analysis by solid-state NMR: structural predictions in ambuic
      acid.
AB  - Relative stereochemistry is predicted for ambuic acid using a novel solid-state
      NMR approach. This NMR technique entails a comparison of measured shift tensor
      principal values with computed values for all diastereomers, allowing the
      selection of a best-fit structure. The proposed method extends previous solution
      NMR structural data by simultaneously modeling with high statistical probability
      hydrogen-bonding arrangements and molecular conformation at two positions. A
      dimeric structure is proposed for ambuic acid based on the initial poor fit of
      the carboxyl carbon tensors to a monomeric model. The dimer model, consisting of
      hydrogen bonding between pairs of neighboring carboxyl groups, reduces the root
      mean square error at the carboxy tensor by a factor of 2.7. Lattice details are
      thus also described by the proposed approach. The structural characterization
      method presented is of general applicability and may be especially useful for
      characterizing difficult to crystallize or hydrogen-poor materials.

PMID- 12790564
TI  - Hydroxymethyl rotamer populations in disaccharides.
AB  - Sixteen methyl glucopyranosyl glucopyranoside disaccharides (methyl beta-d-Glcp(p
      Br-Bz)-(1-->x)-beta/alpha-d-Glcp) containing beta-glycosidic linkages (1-->2, 1-
      >3, 1-->4, and 1-->6) were synthesized and analyzed by means of CD and NMR
      spectroscopy in three different solvents. For each of these four types of
      disaccharides, a correlation was observed between the hydroxymethyl rotational
      populations around the C5-C6 bond of the glucopyranosyl residue II with the
      substituents and the anomeric configuration of the methoxyl group in residue I,
      as well as with the solvent. Nonbonded interactions, the stereoelectronic exo
      anomeric effect, and hydrogen bonding were found to be responsible for the
      observed rotameric differences. Whereas the rotational populations of the (1-->6)
      linked disaccharides are mainly dependent on the exo-anomeric effect, the (1-->2)
      bonded disaccharides are strongly dependent on the anomeric configuration at C1,
      and the (1-->3)- and (1-->4)-linked disaccharides are mainly dependent on the
      substituents and the solvent. The population of the gt rotamer decreases as
      nonbonded interactions increase but increases as the exo-anomeric effect becomes
      greater, as well as in the presence of intramolecular hydrogen bonding to the
      endocyclic oxygen O5'. Comparison of the hydroxymethyl rotational preferences
      between our model disaccharides revealed a dependence on the glycosidic linkage
      type. Thus the population of the gg and gt rotamers decreases/increases from (1-
      >2)- (beta series), to (1-->6)-, to (1-->2)- (alpha series), to (1-->4)-, and to
      (1-->3)-bonded disaccharides respectively, while the tg rotamer population
      remains almost constant (around 20%), except for the (1-->3)- and (1-->4)-linked
      disaccharides with the intramolecular hydrogen bonding to O5', where this
      population decreases to 10%.

PMID- 12790565
TI  - New direct 11B NMR-based analysis of organoboranes through their potassium
      borohydrides.
AB  - Representative organoborane mixtures were quantitatively converted to their
      borohydrides through their reaction with activated KH (KH), permitting their
      detailed analysis by (11)B NMR. Through the treatment of commercial KH with a THF
      solution of lithium aluminum hydride (LAH), a dramatic change in the surface
      morphology results as revealed by scanning electron microscopy (SEM). Energy
      dispersed spectroscopy (EDS) was employed to reveal that the LAH treatment
      deposits a significant amount of an unknown aluminum-containing species on the
      surface of the KH, which imparts a unique reactivity to the KH. Even highly
      hindered organoboranes are quantitatively converted to their borohydrides by
      replacing electronegative groups (e.g., OR, halogen) with hydrogen, retaining
      only the carbon ligation. Through this simple KH treatment, complex organoborane
      reaction mixtures are converted to the corresponding borohydrides whose (11)B NMR
      spectra normally exhibit resolved signals for the individual species present. The
      integration of these signals provides quantitative information on the relative
      amounts of each component of the mixture. New generalities for the effect of
      alpha-, beta-, and gamma-substituents have also been determined that provide a
      new, simple technique for the determination of the isomeric distribution in
      organoborane mixtures resulting from common organoborane processes (e.g.,
      hydroboration). Moreover, the (1)H-coupled (11)B NMR spectra of these mixtures
      reveal the extent of alkylation for each species present. Representative
      organoboranes were examined by this new technique permitting a simple and
      convenient quantitative analysis of the regio- and diastereomeric composition of
      a variety of asymmetric organoborane processes. Previously unknown details of
      pinene-based hydroborations and reductions are revealed for the first time
      employing the KH (11)B NMR technique.

PMID- 12790566
TI  - Synthesis and reactions of fluorous carbobenzyloxy (FCbz) derivatives of alpha
      amino acids.
AB  - Fluorous carbobenzyloxy ((F)Cbz) reagents RfCH(2)CH(2)C(6)H(4)CH(2)OC(O)OSu
      (where Su is succinimidoyl and Rf is C(6)F(13) and C(8)F(17)) have been used to
      make (F)Cbz derivatives of 18 of the 20 natural amino acids. The potential
      utility of this new family of reagents in both standard fluorous synthesis with
      spe separation and fluorous quasiracemic synthesis is illustrated with
      representative reactions of the (F)Cbz-Phe derivatives.

PMID- 12790567
TI  - Computational studies of chiral catalysts: a comparative molecular field analysis
      of an asymmetric Diels-Alder reaction with catalysts containing bisoxazoline or
      phosphinooxazoline ligands.
AB  - A QSAR using Comparative Molecular Field Analysis (CoMFA) is developed for a set
      of 23 catalysts containing bisoxazoline or phosphinooxazoline ligands that are
      known to induce asymmetry during the Diels-Alder reaction of N-2-alkenoyl-1,3
      oxazolidine-2-one with cyclopentadiene. It is shown that extremely high q(2)
      statistics can be derived by using standard modeling protocols when internal
      validation alone is done as well as when an external test set is used. From these
      models it is shown that approximately 70% of the variance in the observed
      enantiomeric excess can be attributed to the steric field and the remainder of
      the variance to the electrostatic field. Suggestions about how to improve the
      performance of inefficient catalysts are given.

PMID- 12790568
TI  - Remote substituent effects on homolytic bond dissociation energies.
AB  - In the study we tried to answer two questions. First, does X-Z homolytic bond
      dissociation energy (BDE) of Y-C6H4-X-Z obey the Hammett relationship? Second, if
      it does what factors determine the magnitude and sign of the slope (rho+) of
      Hammett regression against substituent sigma(p)(+) constants? We collected a
      large number of X-Z BDEs for over one-thousand Y-C6H4-X-Z systems using the
      RMP2/6-311++G**//UB3LYP/6-31G* method. We found that remote substituent effects
      on X-Z BDEs are determined by both the ground effect (i.e.
      stabilization/destabilization of X-Z by the substituents) and the radical effect
      (i.e. stabilization/destabilization of X. by the substituents). The ground or
      radical effect is determined by the electron demand of X-Z or X. in the same way
      as the deprotonation enthalpy of HOOC-C6H4-X-Z or HOOC-C6H4-X. is affected by X-Z
      or X. . As a result, rho+ (BDE) for X-Z bond homolysis can be quantitatively
      predicted by using the change in deprotonation enthalpy from HOOC-C6H4-X-Z to
      HOOC-C6H4-X. .

PMID- 12790569
TI  - Molecular dynamics study of 2rotaxanes: influence of solvation and cation on co
      conformation.
AB  - The conformational preference of a [2]rotaxane system has been examined by
      molecular dynamics simulations. The rotaxane wheel consists of two bridged
      binding components: a cis-dibenzo-18-crown-6 ether and a 1,3-phenyldicarboxamide,
      and the penetrating axle consists of a central isophthaloyl unit with
      phenyltrityl capping groups. The influence of solvation on the co-conformation of
      the [2]rotaxane was evaluated by comparing the conformational flexibility in two
      solvents: chloroform and dimethyl sulfoxide. Attention was also paid to the
      effect of cation binding on the dynamical properties of the [2]rotaxane. The
      conformational stability of the [2]rotaxane was calculated using a MM/PB-SA
      strategy, and the occurrence of specific motions was examined by essential
      dynamics analysis. The changes in the co-conformational properties in the two
      solvents and upon cation binding are discussed in light of the available NMR
      data. The results indicate that in chloroform solution the [2]rotaxane system
      exists as a mixture of co-conformational states including some that have hydrogen
      bonds between axle C=O and wheel NH groups. Analysis of the simulations allow us
      to hypothesize that the [2]rotaxane's circumrotation motion can occur as the
      result of a dynamic process that combines a preliminary axle sliding step that
      breaks these hydrogen bonds and a conformational change in the ester group more
      distant from the wheel. In contrast, no hydrogen-bonded co-conformation was found
      in dimethyl sulfoxide, which appears to be due to the preferential formation of
      hydrogen bonds between the wheel NH groups with solvent molecules. Moreover, the
      axle experiences notable changes in anisotropic shielding, which would explain
      why the NMR signals are broadened in this solvent. Insertion of a sodium cation
      into the crown ether reduces co-conformational flexibility due to an interaction
      of the axle with the cation. Overall, the results reveal how both solvent and
      ionic atmosphere can influence the co-conformational preferences of rotaxanes.

PMID- 12790570
TI  - Irradiation of imine-group VI carbene complexes in the presence of alkynes: a
      theoretical and experimental study.
AB  - The photoreaction between imine-substituted Fischer carbene complexes and alkynes
      is studied at both experimental and theoretical levels. 2H-Pyrrole derivatives
      are easily obtained as main products in moderate to good yields, with complete
      control of the regiochemistry. High-level theoretical calculations are carried
      out in order to explore and fully understand the reaction pathway. On the basis
      of the theoretical results, a mechanism that accounts for the experimental
      findings is proposed.

PMID- 12790571
TI  - The aminobarbituric acid-hydantoin rearrangement.
AB  - A general synthesis protocol for the generation of tri- and tetrasubstituted 5
      carbamoylhydantoins is described. Starting from barbituric acids and following
      bromination and reaction with primary amines, 5-aminobarbituric acids 3a-s and 8
      were prepared. Compounds 3 and 8 were subjected to different conditions of a base
      catalyzed rearrangement reaction to yield the 1,5,5-trisubstituted hydantoins 4a
      s and the 1,3,5,5-tetrasubstituted hydantoin 5c, respectively. Alkylation of 4a-s
      afforded 1,3,5,5-tetrasubstituted hydantoins 5a-h. Mechanisms that explain the
      transformation of corresponding aminobarbituric acids to hydantoins 4a-s and 5c
      were discussed in terms of the formation of ring-opened intermediates.
      Aminobarbituric acids 3a-s unsubstituted at position 3 underwent a ring
      contraction via intermediate isocyanates which were trapped by the amino
      function. A different mechanism involving a carbamate intermediate was concluded
      for conversion of the 1,3,5,5-tetrasubstituted aminobarbituric acid 8.

PMID- 12790572
TI  - Trifluoromethoxy substituted anilines: metalation as the key step for structural
      elaboration.
AB  - Trifluoromethoxy-substituted anilines undergo hydrogen/lithium permutation
      ("metalation") with optional site selectivity depending on the N-protective group
      employed. N-tert-Butoxycarbonyl-2- and -4-(trifluoromethoxy)aniline react with
      tert-butyllithium at the nitrogen-adjacent 6- and 2-position affording, after
      electrophilic trapping, products 1-6. In contrast, deprotonation of the para
      isomer occurs at the oxygen-neighboring 3-position, giving rise to the acid 12,
      when the amino group is carrying two trimethylsilyl groups. sec-Butyllithium
      attacks 3-trifluoromethoxy-N-mono(trimethylsilyl)aniline at the 2-position, but 3
      trifluoromethoxy-N,N-bis(trimethylsilyl)aniline at the 4-position to provide
      respectively the acids 10 and 11 after carboxylation. The synthesis of two new
      benzodiazepines illustrates (19 and 22) the preparative potential of the aniline
      functionalization mediated by organometallic reagents.

PMID- 12790574
TI  - A concise modular synthesis of 2,5-diethynyl-3,4-dibutyl-thiophene-bridged back
      to-back terpyridine ligands.
AB  - The efficient synthesis of soluble and rigid terpyridine-based ditopic ligands
      bearing an increasing number of 2,5-diethynyl-3,4-dibutylthiophene (DEDBT)
      modules has demonstrated the advantages of a single convergent strategy based on
      a double coupling in a final step of monoterpyridine building blocks carrying the
      adequate number of thiophene modules with a diiodo-substituted thiophene subunit.
      This protocol enjoys the advantages of both efficiency and versatility and
      requires pivotal intermediates, which were produced by a step-by-step
      implementation of monoterpyridine fragments with a key thiophene intermediate
      carrying an iodo function, a propargylic-protecting group, and two butyl
      solubilizing fragments. One set of experimental conditions is required to produce
      all the intermediates and the final ligands. Oxidative dimerization of
      monosubstituted terpyridine skeletons bearing one or two thiophene substituents
      and a terminal alkyne function, in the presence of cupric salts and oxygen,
      afforded the homotopic ligands with a central dithienylbutadiyne spacer. Optical
      properties for the new oligomers have been investigated and are discussed in
      terms of effective conjugation length and pi-electron conjugation. Upon
      increasing the number of interspersed DEDBT units, a significant lowering in
      energy of absorption and fluorescence transitions as well as of the quantum
      yields is observed.

PMID- 12790573
TI  - Enantioselective synthesis of the C1-C11 fragment of bafilomycin A1 using non
      Wittig and desymmetrization strategies.
AB  - The synthesis of the C1-C11 fragment 33 of bafilomycin A(1) was achieved.
      Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13.
      Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench
      furnished silyl enol ether 17 with excellent enantioselectivity. Further
      elaboration led to C5-C11 aldehyde 24, which was coupled with sulfone 3 to give
      lactone 25 in very good yield. The subsequent reductive elimination created the E
      trisubstituted C4-C5 olefin with a 13:1 selectivity. The E C2-C3 double bond was
      then installed by methanol elimination, and compound 33 was obtained after a few
      functional group manipulations and a Negishi methyl zirconation.

PMID- 12790575
TI  - Quantitative evaluation of Lewis acidity of metal ions with different ligands and
      counterions in relation to the promoting effects of Lewis acids on electron
      transfer reduction of oxygen.
AB  - The g(zz) values of ESR spectra of superoxide (O(2)(.-) complexes of metal ion
      salts acting as Lewis acids with different ligands and counterions were
      determined in acetonitrile at 143 K. The binding energies (DeltaE) of (O(2)(.
      )/Lewis acid complexes have been evaluated from deviation of the g(zz) values
      from the free spin value. The DeltaE value is quite sensitive to the difference
      in the counterions and ligands of metal ion salts acting as Lewis acids. On the
      other hand, the fluorescence maxima of the singlet excited states of 10
      methylacridone/Lewis acid complexes are red-shifted as compared with that of 10
      methylacridone, and the relative emission energies (Deltahnu(f)) vary
      significantly depending on the Lewis acidity of metal ion salts with different
      counterions and ligands. The promoting effects of Lewis acids were also examined
      on electron transfer from cobalt(II) tetraphenylporphyrin to oxygen in
      acetonitrile at 298 K, which does not occur in the absence of Lewis acids under
      otherwise the same experimental conditions. Both DeltaE and Deltahnu(f) values
      are well correlated with the promoting effects of Lewis acids on the electron
      transfer reduction of oxygen. Such correlations indicate that DeltaE and
      Deltahnu(f) values can be used as quantitative measures of Lewis acidity of metal
      ion salts with different ligands and counterions. The Lewis acidity thus
      determined can also be applied to predict the promoting effects of Lewis acids on
      organic synthesis.

PMID- 12790576
TI  - Synthesis of new chiral 2,2'-bipyridine ligands and their application in copper
      catalyzed asymmetric allylic oxidation and cyclopropanation.
AB  - A series of modular bipyridine-type ligands 1 and 3-9 has been synthesized via a
      de novo construction of the pyridine nucleus. The chiral moieties of these
      ligands originate from the isoprenoid chiral pool, namely, beta-pinene (10 -->
      1), 3-carene (14 --> 3 and 5), 2-carene (28 --> 4), alpha-pinene (43 --> 6-8),
      and dehydropregnenolone acetate (48 --> 9), respectively. Copper(I) complexes,
      derived from these ligands and (TfO)(2)Cu (1 mol %) upon an in situ reduction
      with phenylhydrazine, exhibit good enantioselectivity (up to 82% ee) and
      unusually high reaction rate (typicaly 30 min at room temperature) in allylic
      oxidation of cyclic olefins (52 --> 53). Copper-catalyzed cyclopropanation
      proceeded with < or =76% enantioselectivity and approximately 3:1 to 99:1
      trans/cis-diastereoselectivity (54 --> 55 + 56). The level of the asymmetric
      induction is discussed in terms of the ligand architecture that controls the
      stereochemical environment of the coordinated metal.

PMID- 12790577
TI  - Theoretical study of nucleophilic substitution at the disulfide bridge of cyclo-l
      cystine.
AB  - The reaction of cyclo-l-cystine with thiolate is examined at the B3LYP/6-31+G
      level. The two isomers of cyclo-l-cystine differ in their dihedral angle about
      the disulfide bond; the M isomer (with dihedral angle of -90.1 degrees) is found
      to be slightly lower in energy. The nucleophilic substitution reaction at sulfur
      follows the addition-elimination mechanism, exemplified by the hypercoordinate
      sulfur intermediate on the reaction surface. The reaction is exergonic (DeltaG = 
      6.16 kcal mol(-1)), and both the entrance and exit transition state lie below the
      reactant energies.

PMID- 12790578
TI  - Synthesis and partial biological evaluation of a small library of differentially
      linked beta-C-disaccharides.
AB  - The synthesis of a small library of differentially-linked beta-C-disaccharides
      has been carried out through the use of a radical allylation-RCM strategy. Acids
      6 were prepared by Keck allylation of a suitable carbohydrate-based radical
      precursor, followed by oxidative cleavage of the formed alkene. Dehydrative
      coupling of these acids with the known olefin alcohol 5 then gave the precursor
      esters 7 in excellent yield. Methylenation of the esters 7 was followed by RCM
      and in situ hydroboration-oxidation of the formed glycals to furnish the
      protected beta-C-disaccharides 10 in good overall yield. Five examples were then
      deprotected and screened for their efficacy as enzyme inhibitors of beta
      glycosidase and against several solid-tumor cell lines for in vitro differential
      cytotoxicity.

PMID- 12790580
TI  - A bimetallic catalyst and dual role catalyst: synthesis of N
      (alkoxycarbonyl)indoles from 2-(alkynyl)phenylisocyanates.
AB  - 3-allyl-N-(alkoxycarbonyl)indoles are synthesized via the reaction of 2
      (alkynyl)phenylisocyanates and allyl carbonates in the presence of Pd(PPh(3))(4)
      (1 mol %) and CuCl (4 mol %) bimetallic catalyst. It is most probable that Pd(0)
      acts as a catalyst for the formation of a pi-allylpalladium alkoxide intermediate
      and Cu(I) behaves as a Lewis acid to activate the isocyanate, and the cyclization
      step proceeds with a cooperative catalytic activity of Pd and Cu. On the other
      hand, N-(alkoxycarbonyl)indoles are produced via the reaction of 2
      (alkynyl)phenylisocyanates and alcohols under a catalytic amount of Na(2)PdCl(4)
      (5 mol %) or PtCl(2) (5 mol %). Pd(II) or Pt(II) catalyst exhibits dual roles; it
      acts as a Lewis acid to accelerate the addition of alcohols to isocyanates and as
      a typical transition-metal catalyst to activate the alkyne for the subsequent
      cyclization.

PMID- 12790579
TI  - Solid-phase synthesis of HTLV-1 protease inhibitors containing hydroxyethylamine
      dipeptide isostere.
AB  - An efficient method has been developed for the first solid-phase synthesis of
      HTLV-1 protease inhibitors that contain hydroxyethylamine isostere as a
      transition-state mimetic. The synthetic procedure was designed to allow the
      evaluation of stereostructure-activity relationships at the scissile site. All
      the possible configurations at the hydroxy- and side chain-bearing asymmetric
      centers of the isostere were constructed by an ester-derived asymmetric aldol
      reaction. Each inhibitor containing the isostere backbone was synthesized on
      solid support by using the newly developed succinate ester linker. The
      configuration at the hydroxy- and side chain-bearing asymmetric center showed
      remarkable effects on the inhibitory activity; the K(i) value changed with
      approximately 2 orders of magnitude. The described approach enables an efficient
      preparation of the inhibitors containing secondary alcohol as a transition-state
      mimetic.

PMID- 12790581
TI  - Intra- and intermolecular 1,3-dipolar cycloaddition of sugar ketonitrones with
      mono-, di-, and trisubstituted dipolarophiles.
AB  - The 1,3-dipolar cycloaddition of sugar ketonitrones is a useful synthetic
      procedure to build up nitrogenated quaternary centers in terms of scope
      (substrate, dipolarophile, inter- and intramolecular versions), yield, and regio-
      and stereoselectivity. The hybrid ONIOM (B3LYP/6-31G(d):AM1) theoretical method
      followed by single-point energy calculations at the B3LYP/6-31G(d) level
      adequately perform to model this cycloaddition for the relatively large ketosugar
      precursors commonly used.

PMID- 12790582
TI  - An unexpected highly stereoselective double aza-Baylis-Hillman reaction of
      sulfonated imines with phenyl vinyl ketone.
AB  - The aza-Baylis-Hillman reaction of N-sulfonated imine with phenyl vinyl ketone
      gave the double aza-Baylis-Hillman adduct in good yields with excellent
      stereoselectivities in the presence of Lewis base 1,4-diazabicyclo[2.2.2]octane.

PMID- 12790583
TI  - Synthesis, molecular structure, and applications of 2-hydroxylamino-4,5
      dihydroimidazolium-O-sulfonate to the synthesis of novel heterocyclic ring
      systems.
AB  - 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate (1) has been prepared by
      reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid.
      Deprotonated compound 1a containing both the nucleophilic endocyclic nitrogen
      atoms and electrophilic exocyclic nitrogen was used for the syntheses of 3
      substituted 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]oxadiazoles 2-9 and 6,7-dihydro
      5H-imidazo[2,1-c][1,2,4]thiadiazole-3-thione (10) by tandem nucleophilic addition
      electrophilic amination reaction. The method promises utility in the synthesis of
      a variety of other heterocycles. On the other hand, the convenient routes to 7,8
      dihydroimidazo[1,2-c][1,3,5]thiadiazine-2,4(6H)-dithione (16) and 2,6,7,8
      tetrahydroimidazo[1,2-a][1,3,5]triazine-4(3H)-thione derivative (17) are reported
      starting from compound 1. The structures of the compounds prepared were
      established by elemental analyses, IR, NMR, and MS spectra, and in some instances
      X-ray analyses.

PMID- 12790584
TI  - Nucleophilic epoxidation of gamma-hydroxyvinyl sulfoxide derivatives.
AB  - The nucleophilic epoxidation of simple (gamma-silyloxy)vinyl sulfoxides takes
      place with complete stereocontrol and high yields. For substrates bearing an
      additional substituent at the gamma position, a reinforcing/nonreinforcing
      scenario is operative. While E and Z silylated substrates undergo a primarily
      sulfur directed epoxidation with good to excellent diastereocontrol, the related
      (E)-(2-methoxyethoxy)methyl ethers display diminished selectivity for the
      diastereomer derived from the nonreinforcing scenario.

PMID- 12790585
TI  - Design and synthesis of tridentate facially chelating ligands of the [2.n.1]
      (2,6)-pyridinophane family.
AB  - Syntheses are reported for tripyridine macrocycles 2 and 3 and some of their
      alkyl derivatives. The macrocycles are designed to stabilize to various extents
      coordinated d(8) metal precursors and d(6) alkane oxidative addition products
      (Pt(IV)), therefore allowing favorable kinetics and thermodynamics of (e.g.,
      Pt(II)) the cleavage of substrate H-C(sp(3)) bonds. Both the Chichibabin protocol
      and oxidative coupling of carbanions by copper(I) iodide were used for the
      macrocyclization step. Crystal structures of singly and doubly protonated 2
      establish atom connectivity in the macrocycle, and reveal structural features
      which are obscured in solution NMR by rapid proton migration.

PMID- 12790586
TI  - An efficient route to chiral alpha- and beta-hydroxyalkanephosphonates.
AB  - Enzymatic kinetic resolution of alpha- and beta-hydroxyphosphonates in
      combination with ruthenium-catalyzed alcohol isomerization led to a successful
      dynamic kinetic resolution. A variety of racemic hydroxyphosphonates were
      efficiently transformed to the corresponding enantiomerically pure acetates (ee
      up to 99% and yield up to 87%).

PMID- 12790587
TI  - Inter- and innermolecular reactions of chloro(phenyl)carbene.
AB  - Supramolecular photolyses of 3-chloro-3-phenyl-3H-diazirine (8) were performed
      within cyclodextrin (CyD) hosts to determine whether these toroidal inclusion
      compounds could alter the reactivity of the ensuing carbene reaction
      intermediate, chloro(phenyl)carbene (9). Remarkably, no intramolecular products
      stemming from carbene 9 could be detected. Instead, modified CyDs were formed via
      so-called innermolecular reactions. Hence, diazirine 8 was photolyzed in various
      conventional solvents to gauge the intermolecular reactivity of carbene 9.
      Relevant results were used to rationalize the CyD innermolecular reaction
      products.

PMID- 12790588
TI  - Epoxides, cyclic sulfites, and sulfate from natural pentacyclic triterpenoids:
      theoretical calculations and chemical transformations.
AB  - Several triterpenic derivatives, with the A-ring functionalized, were
      semisynthesized from oleanolic and maslinic acids. The reactivities of sulfites,
      sulfate, and epoxides in these triterpene compounds were investigated under
      different reaction conditions. Moreover, contracted A-ring triterpenes (five
      membered rings) were obtained, by different treatments of the sulfate 7. From the
      epoxide 8, deoxygenated and halohydrin derivatives were semisynthesized with
      several nucleophiles. Ozonolysis and Beckmann reactions were used to yield 4-aza
      compounds, from five-membered ring olanediene triterpenes. The X-ray structure of
      sulfate 7 is given and compared with density functional theory geometries.
      Theoretical (13)C and (1)H chemical shifts (gauge-invariant atomic orbital method
      at the B3LYP/6-31G*//B3LYP/6-31G* level) and (3)J(H,H) coupling constants were
      calculated for compounds 5-9 and 34-36, identifying the (R)- or (S)-sulfur and
      alpha- or beta-epoxide configurations together with 4-aza or 3-aza structures.

PMID- 12790589
TI  - Syntheses of functionalized 1,4-disubstituted gamma-carbolines.
AB  - We report the complete synthesis of a variety of 1,4-disubstituted gamma
      carbolines. These compounds are of particular interest for their involvement in
      many biological processes and are believed to possess various medicinal
      activities. A large number of N-tosylaldimines were condensed with indoles
      affording an array of 3-aminomethyl indoles. Subsequent additions, followed by
      intramolecular cyclization, afforded an array of 1,2-dihydro-3H-gamma-carbolones
      in good yield. Upon subsequent aromatization, the corresponding fully aromatic
      functionalized 1-aryl-4-hydroxy-gamma-carbolines resulted.

PMID- 12790590
TI  - Fullerene anions of different sizes and shapes: a 13C NMR and density-functional
      study.
AB  - A combined experimental and theoretical study was conducted on numerous higher
      fullerene anions with different sizes and shapes, C76-D2, C78-C2v, C78-D3, C84
      D2, and C84-D2d. The corresponding fullerenes were reduced by lithium metal to
      diamagnetic multiply charged anions. The centers of gravity of the 13C NMR
      spectra of all the multiply charged anions were deshielded, relative to those of
      the neutral fullerenes. The results of density functional (DFT) computations of
      the 13C NMR spectra and the molecular orbitals (MOs) of possible polyanion
      reduction products suggest that hexaanions were the species formed.

PMID- 12790591
TI  - Photochemistry of phenyl-substituted 1,2,4-thiadiazoles. 15N-labeling studies.
AB  - Irradiation of 5-phenyl-1,2,4-thiadiazole (6) resulted in the formation of
      benzonitrile (5), 3-phenyl-1,2,4-thiadiazole (4), phenyl- and diphenyl-1,3,5
      triazines (7 and 8), and a trace quantity of diphenyl-1,2,4-thiadiazole (9). The
      formation of 4,5, 7, and 8 can be explained in terms of photoinduced
      electrocyclic ring closure resulting in the formation of an intermediate 4-phenyl
      1,3-diaza-5-thiabicyclo[2.1.0]pentene. 15N-labeling experiments revealed that
      sulfur can undergo sigmatropic shifts around all four sides of the diazetine
      ring. Thus, irradiation of 6-4-15N led to the formation of 6-2-15N and an
      equimolar mixture of 4-2-15N and 4-4-15N. The thiabicyclo[2.1.0]pentene
      intermediate is also suggested to undergo sulfur elimination resulting in the
      formation of phenyldiazacyclobutadiene, which can undergo complete fragmentation
      to benzonitrile or [4+2] cycloaddition leading to unstable tricyclic adducts, the
      suggested precursors of the 1,3,5-triazine products 7 and 8. The observed 15N
      distribution in 7 and 8 is consistent with this mechanism. Irradiation of 4 led
      only to the formation of 5. 15N-labeling experiments show that 4 does not undergo
      electrocyclic ring closure but reacts exclusively by photofragmentation of the
      thiadiazole ring.

PMID- 12790592
TI  - Nanoscale tripodal 1,3,5,7-tetrasubstituted adamantanes for AFM applications.
AB  - The synthesis of four novel nanoscale 1,3,5,7-tetrasubstituted adamantanes 22 and
      25-27 designed for atomic force microscopy (AFM) applications is described. Each
      tetrahedrally shaped molecule incorporates a broad tripodal base made up of three
      identical legs that terminate with a sulfur-containing moiety, which is either a
      4-acetylsulfanylmethylphenyl unit or else a (1,2,5-dithiazepan-1-yl)phenyl unit.
      The sulfur atoms are intended for eventual binding of the molecule multivalently
      to the apex of a gold-coated commercial AFM tip through formation of multiple S
      Au bonds. In each molecule, the fourth terminus is a para-substituted benzoic
      acid methyl ester that is designed to scan the sample. We demonstrate that 27 is
      sufficiently large and rigid to be imaged by a conventional AFM tip. Adamantanes
      22 and 25-27 may also find application as chemically well-defined nanoscale
      objects for calibration of AFM tips.

PMID- 12790593
TI  - Rapid SmI2-mediated reductions of alkyl halides and electrochemical properties of
      SmI2/H2O/amine.
AB  - Mixtures of SmI(2)/H(2)O/amine have been found to reduce alkyl halides more
      efficiently than SmI(2)/HMPA/alcohol mixtures at room temperature. Alkyl and aryl
      iodides were quantitatively reduced in <1 min and alkyl bromides in 10 min, while
      alkyl and aryl chlorides required more than 5 h for completion. Determination of
      the reaction order of Et(3)N in the reduction of 1-chlorodecane showed that the
      reaction order is one. Water was shown not to participate in the rate-determining
      step of this reduction. There was a significant change of the UV-vis spectrum and
      color of SmI(2) upon addition of either PMDTA or water, while no effect was
      observed with the addition of Et(3)N or TMEDA. Although the combination of
      SmI(2), water, and amines produces a very efficient reducing system, cyclic
      voltammetric experiments showed that the redox potential is nearly identical with
      that of SmI(2) alone. These results are consistent with precipitation providing
      the driving force for reduction. Taken together, the results of these experiments
      show that the combination of SmI(2)/H(2)O/amine provides a fundamentally novel
      and useful approach to enhance the reactivity of SmI(2).

PMID- 12790594
TI  - Synthesis and reactions of 2-substituted ethyl N-alkylmalonylhydroxamic acids.
AB  - Alkylation of O-silylated N-alkylmalonylhydroxamic acids provides a method for
      the synthesis of 2-substituted N-alkylmalonyl hydroxamic acids. The substituent
      at C-2 does not materially change the chemistry of the alpha-lactam intermediates
      produced from them. They can be converted to unsymmetric ureas and hydantoins in
      high yields. The addition of unsaturated substituents at C-2 is used to produce
      cyclic ureas containing medium rings via RCM reactions.

PMID- 12790595
TI  - A novel alpha-arylation of ketones, aldehydes, and esters via a photoinduced SN1
      reaction through 4-aminophenyl cations.
AB  - 4-Aminophenyl cations (expediently generated by photolysis of 4-chloroaniline and
      its N,N-dimethyl derivative by photolysis in MeCN) added to enamines and gave the
      corresponding alpha-(4-aminophenyl) ketones in satisfactory yields. The yields of
      the same ketones were increased when silyl enol ethers were used in the place of
      enamines. The alpha-arylation of silyl enol ethers of aldehydes occurred with
      lower yields and only with the N,N-dimethyl derivative. The procedure was
      successful with ketene silyl acetals giving in a single step a good yield of
      alpha-(4-aminophenyl)propionic(acetic) esters, known intermediates for the
      preparation of analgesic compounds. The reaction of the aryl cation with
      Danishefsky's diene gave the arylated beta-methoxy enone. The method is
      complementary to the recently developed palladium-catalyzed alpha-arylation and
      occurs under neutral conditions.

PMID- 12790596
TI  - Synthesis, isolation, and characterization of 2'-paclitaxel glycinate: an
      application of the Bsmoc protecting group.
AB  - The relevance of the Bsmoc protecting group in the synthesis of moisture- and
      base-sensitive compounds has been demonstrated by the preparation of 2'
      paclitaxel glycinate with use of the solid anhydrous base, 4-piperidinopiperidine
      in DCM solvent.

PMID- 12790597
TI  - Asymmetric synthesis of an axially chiral antimitotic biaryl via an atropo
      enantioselective Suzuki cross-coupling.
AB  - A catalytic asymmetric synthesis of the axially chiral bridged biaryl (-)-2, a
      structural analogue of natural (-)-rhazinilam possessing original antimitotic
      properties, is described. The key step is an intermolecular asymmetric Suzuki
      coupling, furnishing the nonbridged biaryl (-)-6, precursor of (-)-2, with up to
      40% ee using binaphthyl ligand 7a. Various known or new binaphthyl and ferrocenyl
      phosphines as well as phosphetanes were screened as ligands in this reaction, the
      conditions of which were optimized. The comparison with another Suzuki coupling
      system showed that 7a is the most versatile ligand described to date for this
      type of transformation. This work gives the first application of the asymmetric
      Suzuki coupling to a biologically relevant target.

PMID- 12790598
TI  - Photolysis of chiral 1-pyrazolines to cyclopropanes: mechanism and
      stereospecificity.
AB  - The photodenitrogenation of chiral trisubstituted 1-pyrazolines has been studied
      by laser flash photolysis. These experiments have permitted the detection of two
      transients that have been assigned, for each pyrazoline, to the trimethylene-type
      diradical resultant from the extrusion of nitrogen (lifetime tau = 0.1-0.8
      micros) and to the pyrazoline triplet (tau < 9 ns), respectively. The efficiency
      of the photosensitization process has been evaluated by determination of the
      corresponding quenching rate constant in each instance. Theoretical calculations
      support a mechanistic pathway involving a trimethylene radical as intermediate
      that rapidly evolves to the corresponding cyclopropane derivative. The
      cyclopropane ring-closure is predicted to be faster than rotation around the C-C
      bond, thus accounting for the observed stereospecificity.

PMID- 12790599
TI  - From thiourea to bicyclic structures: an original route to imidazo[2,1
      b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and
      2H,6H-pyrimido[2,1-b][1,3]thiazines.
AB  - We report an example of an efficient regioselective synthesis of biheterocyclic
      compounds using thiourea as starting material. In fact, N,N'
      bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation
      of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with
      haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3)
      diazadienes, respectively, themselves undergoing cyclization reactions to yield
      imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1
      b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any
      regioisomeric ambiguity. This straightforward route represents an original and
      unambiguously regioselective pathway to these valuable heterocycles.

PMID- 12790600
TI  - First regioselective ortho-lithiation induced by a 2-chloropyridyl group
      complexation.
AB  - It is shown that t-BuLi in Et(2)O promotes an exclusive regioselective metalation
      of 2-aryl-6-chloropyridine compounds at the aromatic ortho position demonstrating
      that the 2-chloropyridyl moiety may be considered as a directing group. This
      functionally directed metalation group was successfully used for the selective
      lithiation of substituted aromatics and for the straightforward preparation of
      new N,P ligands.

PMID- 12790601
TI  - Synthesis of enantiopure 3-azabicyclo[3.2.0]heptanes by diastereoselective
      intramolecular [2+2] photocycloaddition reactions on chiral perhydro-1,3
      benzoxazines.
AB  - [2+2] photocycloadditions involving chiral 3-acryloyl-2-vinylperhydro-1,3
      benzoxazines derived from (-)-8-aminomenthol are highly diastereoselective
      reactions. The facial selectivity depends on the type of substitution at the
      vinyl double bond, and always leads to cis-fused bicyclic derivatives. The de is
      good for compounds with one substituent at the outer carbon of the double bond at
      C-2, but only one diastereomer is formed in cyclizations of compounds with two
      substituents at that position. The elimination of the menthol appendage gives
      enantiopure 3-azabicyclo[3.2.0]heptanes.

PMID- 12790602
TI  - Expedient acylations of primary and secondary alkyl cyanides to alpha-substituted
      beta-ketonitriles.
AB  - Primary and secondary cyanides are efficiently acylated with N-acylbenzotriazoles
      3a-f (derived from a variety of acids) to afford the corresponding alpha
      substituted beta-ketonitriles 5a-r in 67-96% yields.

PMID- 12790603
TI  - Regiospecific synthesis of 3-substituted imidazo[1,2-a]pyridines, imidazo[1,2
      a]pyrimidines, and imidazo[1,2-c]pyrimidine.
AB  - 3-Substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2
      c]pyrimidine were obtained regiospecifically in yields of 35-92% in one pot by
      reaction of 2-aminopyridines or 2-(or 4-)aminopyrimidines, respectively, with 1,2
      bis(benzotriazolyl)-1,2-(dialkylamino)ethanes.

PMID- 12790604
TI  - Novel Synthesis of 1,2,3,4-Tetrahydropyrazino[1,2-a]indoles.
AB  - Condensation of 2-(3-methyl-1H-indol-1-yl)ethylamine (7) with benzotriazole and
      formaldehyde gave 2-(1H-1,2,3-benzotriazol-1-ylmethyl)-10-methyl-1,2,3,4
      tetrahydropyrazino[1,2-a]indole (8) in 96% yield. Nucleophilic substitutions of
      the benzotriazolyl group in 8 with NaBH(4), NaCN, triethyl phosphite,
      allylsilanes, silyl enol ether and Grignard reagents afforded novel 10-methyl
      1,2,3,4-tetrahydropyrazino[1,2-a]indoles 9a-i in 78-95% yields.

PMID- 12790605
TI  - A general route to 5-aminotetrazoles.
AB  - Various di- and trisubstituted (benzotriazolyl)carboximidamides were used for the
      preparation of N,N-di- and 1,N,N-trisubstituted 5-aminotetrazoles 3a-e and 6a-d
      under mild conditions in good to excellent yields.

PMID- 12790606
TI  - Preparation of enantiopure 1-azabicyclo[3.2.2]nonanes functionalized at carbon
      C3, from cinchonine and cinchonidine. stereoselective solvolysis and an easily
      enolizable ketone.
AB  - Solvolysis of C9 mesylated cinchonidine 1-OMs and cinchonine 2-OMs in solvent
      MeOH, EtOH, and CF(3)CH(2)OH affords ring-expanded 1-azabicyclo[3.2.2]nonanes
      oxygenated at carbon C3 ("second Cinchona rearrangement"). The newly introduced
      substituents at C3 and the neighboring quinolyl group Q' at C2 adopt
      quasiequatorial positions. The derived 1-azabicyclo[3.2.2]nonan-3-ones 5 and 6
      are easily equilibrated. On contact with MeOD uptake of deuterium takes place at
      room temperature.

PMID- 12790607
TI  - Acid-promoted reaction of trimethylsilylketene bis(ethylthio)acetal with imines.
      Synthesis of gamma,gamma-bis(ethylthio)allylamines.
AB  - Acid-catalyzed reaction of silylketene dithioacetal 1 with iminium salts or
      imines 3b,d-h gave the corresponding gamma,gamma-bis(ethylthio)allylamines 2a-h
      or 5b,d-h in generally high yields. Similar reactions of 1 with
      (salicylidene)amines 6a-e afforded 4-amino-2,2-bis(ethylthio)chromans 8a-e in
      good to moderate yields.

PMID- 12790608
TI  - Lithium trifluoromethanesulfonate (LiOTf) as a recyclable catalyst for highly
      efficient acetylation of alcohols and diacetylation of aldehydes under mild and
      neutral reaction conditions.
AB  - A variety of alcohols and aldehydes were reacted with acetic anhydride at room
      temperature in the presence of a catalytic amount of lithium triflate (LiOTf) to
      produce the corresponding esters and 1,1-diacetates, respectively, in good to
      excellent yields under essentially neutral reaction conditions. Sensitive
      functional groups such as PhCO(2)-, OMe, and OTBDMS ethers survived intact under
      the described reaction conditions.

PMID- 12790609
TI  - Iron(II)-catalyzed sulfimidation and [2,3]-sigmatropic rearrangement of propargyl
      sulfides with tert-butoxycarbonyl azide. Access to N-allenylsulfenimides.
AB  - The iron(II)-catalyzed Bach reaction of tert-butoxycarbonyl azide (BocN(3)) and
      allyl sulfides has been extended to include propargyl sulfides, which give N
      allenylsulfenimide products. Using 10 mol % dppeFeCl(2) as catalyst the reaction
      proceeds at 0 degrees C with a number of different propargyl sulfides in 31-73%
      isolated yield. The reaction is limited by product instability toward catalyst
      and termination of the catalytic cycle by excess BocN(3). N-Allenylsulfenimide 2b
      smoothly undergoes catalytic hydrogenation and a Diels-Alder reaction with
      cyclopentadiene.

PMID- 12790610
TI  - Addition of water to zinc triflate promotes a novel reaction: stereoselective
      Mannich-type reaction of chiral aldimines with 2-silyloxybutadienes.
AB  - A novel stereoselective Mannich-type reaction of chiral aldimines with 2
      silyloxybutadienes in the presence of zinc triflate and water has been achieved.
      The diastereoselectivities of the products were 74-90% de, and no cycloadducts
      were detected. Classical Mannich-type products were also obtained by using zinc
      triflate and water with high diastereoselectivities.

PMID- 12790611
TI  - An improved synthesis of a ketone catalyst for asymmetric epoxidation of olefins.
AB  - An efficient synthesis of a ketone catalyst for asymmetric epoxidation of olefins
      from D-glucose in six steps is described.

PMID- 12790612
TI  - Sequoiamonascins a-d: novel anticancer metabolites isolated from a redwood
      endophyte.
AB  - Aspergillus parasiticus, a fungal isolate from the bark of a redwood tree
      (Sequoia sempervirens), has been shown to produce the antitumor metabolites
      sequoiatones A and B and more recently the sequoiatones C-F. We have also
      isolated another series of compounds with a new carbon skeleton, the
      sequoiamonascins. The structures of sequoiamonascins A-D were deduced by
      interpretation of their spectral data and that of some reaction products. The
      sequoiamonascins were isolated by brine shrimp lethality-guided fractionation and
      were submitted to the NCI for anticancer evaluation.

PMID- 12790613
TI  - Synthesis of louisianin C.
AB  - The synthesis of louisianin C (3), a member of a small family of 3,4,5
      trisubstituted pyridyl natural products, is achieved in six steps and 11% overall
      yield starting from commercially available 3,5-dibromopyridine. The key step is a
      fluoride-induced desilylation-cyclization to afford carbinol 12.

PMID- 12790614
TI  - Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of
      nucleophilic glycine equivalent.
AB  - An efficient, easy to scale-up method for preparing 2-aminoindane-2-carboxylic
      acid via two-step alkylation of a Ni(II)-complex of glycine Schiff base with 2-[N
      (alpha-picolyl)amino]benzophenone (PAAP) (2b) with o-dibromoxylylene (3) is
      reported. The first step, monoalkylation of 2b with 3, conducted under phase
      transfer conditions, gave the corresponding complex 6 in excellent chemical yield
      (97.2%). Without any purification the intermediate 6 was cyclized under
      homogeneous conditions (DMF, NaO-t-Bu) to give the product 7 in high chemical
      yield (93.1%). Decomposition of prepared 7 afforded the target amino acid 2
      aminoindane-2-carboxylic acid (1) in 97.9% yield, along with recovery of ligand
      8, which was converted back to the starting glycine complex 2b. Operationally
      convenient experimental procedures, mild reaction conditions, as well as high
      chemical and volume yields render the method practical for preparing amino acid 1
      and its analogues.

PMID- 12790615
TI  - Isolation and characterization of kallosin A, a novel rearranged pseudopterane
      diterpenoid from the Caribbean sea plume Pseudopterogorgia kallos (Bielschowsky).
AB  - The Caribbean alcyonacean Pseudopterogorgia kallos is shown to contain a novel
      rearranged pseudopterane diterpene, kallosin A (1), possessing several unusual
      structural features. In addition to having two distinct 2(3H)- and 2(5H)-furanone
      moieties, kallosin A is based on a new carbon skeleton. The structural assignment
      of 1 was based mainly on 1D and 2D NMR spectral data and was further supported by
      accurate mass measurement and single-crystal X-ray diffraction analysis.

PMID- 12790616
TI  - Efficient and practical method for synthesizing optically active indan-2-ols by
      the Ti(O-i-Pr)(4)/2 i-PrMgCl-mediated metalative Reppe reaction.
AB  - An efficient and practical synthesis of optically active indan-2-ols 1 has been
      developed starting from readily accessible optically active 4-siloxy-1,6
      alkadiynes 2 and ethynyl p-tolyl sulfone, where the metalative Reppe reaction
      mediated by an economical divalent titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, is
      a key step.

PMID- 12790617
TI  - A novel enantioselective alkylation and its application to the synthesis of an
      anticancer agent.
AB  - A novel enantioselective alkylation of double benzylic substrates with secondary
      electrophiles is reported. A simple norephedrine-based chiral ligand was
      synthesized that gives alkylation product in 95% yield and 95% ee. A unique water
      effect on the enantioselectivity was unveiled. Good to excellent ee values were
      obtained with a number of double benzylic substrates and secondary electrophiles.
      This novel reaction has been applied to the synthesis of a promising anticancer
      agent.

PMID- 12790618
TI  - Regiospecificity in the synthesis of diaryl sulfones.
AB  - The addition of arylsulfinic acids to 2-methyl-1,4-benzoquinone provides high
      yields of sulfones in a wide variety of solvents. The distribution of isomeric
      products obtained is strongly influenced by either (1) the acidity of aqueous
      solvents or (2) the water content of alcohol solvents. The distribution of
      isomeric products does not change in the various anhydrous, aprotic solvents
      examined.

PMID- 12790619
TI  - Revision and confirmation of the regiochemistry of isoxazoles derived from methyl
      oleanonate and lanost-8-en-3-one. Synthesis of a new lanostane triterpenoid with
      a cyano-enone functionality in ring A.
AB  - It was previously reported that methyl oleanonate (5) and lanost-8-en-3-one (10)
      give predominantly [3,2-c]isoxazoles. On the contrary, we have confirmed that
      both compounds 5 and 10 do not give [3,2-c]isoxazoles but rather afford
      regioselectively [2,3-d]isoxazoles in good yields. Consequently, a new lanostane
      triterpenoid with a cyano-enone functionality in ring A was synthesized in two
      steps from the corresponding [2,3-d]isoxazole, which is interesting from the
      perspective of biological activity because lanosterol is the biogenetic precursor
      of steroids.

PMID- 12790620
TI  - Highly regioselective ring opening of oxiranes with phenoxides in the presence of
      beta-cyclodextrin in water.
AB  - Highly regioselective ring opening of oxiranes to beta-hydroxy ethers with
      phenoxides has been achieved in impressive yields in the presence of beta
      cyclodextrin as catalyst and water as solvent.

PMID- 12790621
TI  - Convenient synthesis of 2-benzazepines via radical cyclization.
AB  - Synthesis of 2-benzazepines was readily achieved via 7-endo radical cyclization
      of N-o-bromobenzylitaconamides or N-o-bromobenzylmethacrylamides which were
      prepared in two steps from commercially available benzaldehydes, amines, and
      alpha,beta-unsaturated acids.

PMID- 12790622
TI  - Trichloroisocyanuric/TEMPO oxidation of alcohols under mild conditions: a close
      investigation.
AB  - Efficient oxidation of primary alcohols to the corresponding carboxylic acids can
      be carried out at room temperature and in acetone/water, using
      trichloroisocyanuric acid (TCCA) in the presence of catalytic TEMPO. The mild
      conditions of this procedure and the total absence of any transition metal make
      this reaction suitable for safe laboratory use. A possible mechanism is presented
      and discussed.

PMID- 12790623
TI  - Sulfinyl moiety as an internal nucleophile. 1. Efficient stereoselective
      synthesis of fragment a of cryptophycin 3.
AB  - A novel, efficient, and stereoselective synthesis of fragment A of cryptophycin 3
      is disclosed. The key step involves the regio- and stereoselective transformation
      of an unsaturated ester to a bromohydrin via anchimeric assistance by the
      sulfinyl group.

PMID- 12790624
TI  - Synthesis of a novel cis-proline-derived cyclic type VI beta-turn mimic via ring
      closing metathesis.
AB  - A cis-proline derived cyclic mimic of a type VI beta-turn is synthesized via a
      ring-closing metathesis reaction. The solution NMR conformational study indicates
      that the major conformer of the cyclic peptide adopts a type VIa beta-turn in
      CDCl(3) and a type VIb beta-turn in DMSO-d(6).

PMID- 12790625
TI  - Retrocyclopropanation reactions of fullerenes: complete product analyses.
AB  - Mono- and bis-pyrene malonates 1 and 2 were synthesized and reacted with C(60) to
      prepare the corresponding Bingel adducts 3 and 4. These compounds were
      characterized electrochemically and exhibited the well-established
      retrocyclopropanation reaction when subjected to bulk electrolytic reductions.
      For the first time, it was possible to perform detailed product analyses after
      the retrocyclopropanation reactions, and these showed the presence of the
      original malonates 1 and 2 along with C(60), in reasonable yields, around 50%.

PMID- 12790626
TI  - Advance and prospect of bionanomaterials.
AB  - Over the past few years, bionanomaterial science has emerged as a new exciting
      field in which theoretical and experimental studies of structure and function of
      bionanomaterials have become a focus, and the importance of DNA, RNA, and
      peptides as bionanomaterials to the fundamental development in biology and
      nanomaterials has begun to be recognized. In particular, biochemistry,
      biophysics, biomechanics, thermodynamics, and electronic properties of DNA, RNA,
      and peptides, as well as intelligent composite biological materials, have become
      a new interdisciplinary frontier in life science and material science. There is
      an increasing need for a more systematic study of the basic issues involved in
      bionanomaterials and a more active participation of researchers in the
      application domain of such novel materials. Great advances have been and are
      being made in nanobiochip materials, nanoscale biomimetic materials, nanomotors,
      nanocomposite materials, interface biomaterials, and nanobiosensor and nano drug
      delivery systems, with enormous prospect in industrial, defense, and clinical
      medicine applications. Here we review some of the main advances in this field
      over the past few years, explore the application prospects, and discuss the
      concepts, issues, approaches, and challenges, with the aim of stimulating a
      broader interest in developing bionanomaterials technology.

PMID- 12790627
TI  - Design and installation of a next generation pilot scale fermentation system.
AB  - Four new fermenters were designed and constructed for use in secondary metabolite
      cultivations, bioconversions, and enzyme production. A new PC/PLC-based control
      system also was implemented using GE Fanuc PLCs, Genius I/O blocks, and Fix
      Dynamics SCADA software. These systems were incorporated into an industrial
      research fermentation pilot plant, designed and constructed in the early 1980s.
      Details of the design of these new fermenters and the new control system are
      described and compared with the existing installation for expected effectiveness.
      In addition, the reasoning behind selection of some of these features has been
      included. Key to the design was the goal of preserving similarity between the new
      and previously existing and successfully utilized fermenter hardware and software
      installations where feasible but implementing improvements where warranted and
      beneficial. Examples of enhancements include strategic use of Inconel as a
      material of construction to reduce corrosion, piping layout design for simplified
      hazardous energy isolation, on-line calculation and control of nutrient feed
      rates, and the use of field I/O modules located near the vessel to permit low
      cost addition of new instrumentation.

PMID- 12790628
TI  - Carbon material and bioenergetic balances of xylitol production from corncobs by
      Debaryomyces hansenii.
AB  - The effect of oxygenation on xylitol production by the yeast Debaryomyces
      hansenii has been investigated in this work using the liquors from corncob
      hydrolysis as the fermentation medium. The concentrations of consumed substrates
      (glucose, xylose, arabinose, acetate and oxygen) and formed products (xylitol,
      arabitol, ethanol, biomass and carbon dioxide) have been used, together with
      those previously obtained varying the hydrolysis technique, the level of
      adaptation of the microorganism, the sterilization procedure and the initial
      substrate and biomass concentrations, in carbon material balances to evaluate the
      percentages of xylose consumed by the yeast for the reduction to xylitol, alcohol
      fermentation, respiration and cell growth. The highest xylitol concentration (71
      g/L) and volumetric productivity (1.5 g/L.h) were obtained semiaerobically using
      detoxified hydrolyzate produced by autohydrolysis-posthydrolysis, at starting
      levels of xylose (S(0)) and biomass (X(0)) of about 100 g/L and 12 g(DM)/L,
      respectively. No less than 80% xylose was addressed to xylitol production under
      these conditions. The experimental data collected in this work at variable oxygen
      levels allowed estimating a P/O ratio of 1.16 mol(ATP)/mol(O). The overall ATP
      requirements for biomass production and maintenance demonstrated to remarkably
      increase with X(0) and for S(0) >or= 130 g/L and to reach minimum values (1.9-2.1
      mol(ATP)/C-mol(DM)) just under semiaerobic conditions favoring xylitol
      accumulation.

PMID- 12790629
TI  - Metabolite profiles and growth characteristics of Rhizobium meliloti cultivated
      at different specific growth rates.
AB  - Rhizobium meliloti (ATCC 55340) was grown at different specific growth rates in a
      chemostat apparatus. Metabolic products, relating to the Embden-Meyerhof-Parnas
      (EMP) pathway and the tricarboxylic acid (TCA) cycle, were measured and
      quantified to probe the influence of specific growth rate on the distribution of
      important metabolites. The detection of propionate in the fermentation broth
      implies that the imbalance of reducing equivalents of FADH(2) and NADH + H(+)
      resulted in a partially reductive operation of the TCA cycle. Additionally,
      experimental results show that the specific growth rate plays an essential role
      in modulating the biomass concentration, the specific substrate uptake rate, the
      cell length, the specific exopolysaccharide (EPS) production rate, the
      distribution of EPS molecular weight, and the profiles of carbohydrate and
      organic acid. The specific EPS production rate (varying from 13.3 to 111 mg EPS/g
      DW/h) follows a growth-associated pattern at the specific growth rate ranging
      from 0.06 to 0.20 h(-1) and switches into non-growth-associated mode when the
      specific growth rate is over 0.20 h(-1).

PMID- 12790630
TI  - Protein-protein interaction conferring stability to an extracellular acetyl
      (xylan) esterase produced by Termitomyces clypeatus.
AB  - Acetyl esterase (AE) activity present in the culture filtrate of Termitomyces
      clypeatus was separated into lower molar mass (LMM) and higher molar mass (HMM)
      protein fractions during BioGel P-200 gel chromatography. AE was purified as a 30
      kDa nonglycosylated protein from LMM fractions by CM-Sepharose ion exchange
      chromatography and HPGPLC. Although the HMM fraction had a number of enzyme
      activities (sucrase, beta-xylosidase, beta-glucosidase, and alpha-L
      arabinofuranosidase) other than AE, protein present in the fraction was eluted as
      a single protein peak in HPGPLC and gave a single band in native PAGE. The
      fraction, subsequently purified by DEAE-Sephadex chromatography, was a SDS-PAGE
      homogeneous 80 kDa glycoprotein, but with both AE and cellobiase activities. The
      aggregate dissociated during ConA-Sepharose chromatography and 30 kDa AE and 56
      kDa glycosylated cellobiase were purified separately. The dissociation caused
      significant loss of cellobiase activity but not that of AE. AE purified from both
      HMM and LMM fractions was characterized to be the same enzyme in terms of molar
      masses, pI (7.3), and other physicochemical properties. AE as an aggregate with
      cellobiase showed higher thermostability, temperature optimum, and resistance
      toward chemical denaturants than those of purified AE. Compared to cellobiase
      purified earlier from the same fungus, the enzyme present with AE in the
      aggregate also showed higher catalytic activity, thermostability, and temperature
      optimum. The study indicated that the formation of such SDS-resistant enzyme
      aggregate was associated with significant changes in the physicochemical
      properties of the enzymes, mainly toward improvement of rigidity of enzymes, and
      sometimes with the improvement of catalytic activity.

PMID- 12790631
TI  - New system for positive selection of recombinant plasmids and dual expression in
      yeast and bacteria based on the restriction ribonuclease RegB.
AB  - By coupling the toxic restriction endoribonuclease RegB, from the bacteriophage
      T4, to the prokaryotic T7 and the eukaryotic GAL1 promoters, we constructed a two
      function plasmid called pTOXR-1. This plasmid is a zero-background cloning
      vector. It allows an efficient positive selection of recombinant plasmids without
      the need to completely digest, dephosphorylate, or purify the vector prior to the
      ligation step. The pTOXR-1 positive selection system requires no special
      Escherichia coli strains, no special culture media, and no addition of inducer to
      the selective plates. In addition, since this vector carries all signals required
      for both prokaryotic and eukaryotic expression, it allows the overproduction of
      heterologous proteins, fused to a polyhistidine tag, in the bacterium E. coli and
      in the yeast Saccharomyces cerevisiae from a single plasmid. Hence, this vector
      may be a useful time-saving tool for one-step cloning and versatile protein
      expression in bacteria and yeast.

PMID- 12790632
TI  - Small RNA sequences are readily stabilized by inclusion in a carrier rRNA.
AB  - This laboratory previously showed that an RNA derived from 5S ribosomal RNA could
      be used as a carrier to harbor a nucleic acid "tag" for monitoring genetically
      engineered or naturally occurring bacteria. The prototype system expressed a
      specific tagged RNA that was stable and accumulated to high levels. For such a
      system to be useful there should, however, be little limitation on the sequence
      composition and length of the insert. To test these limitations, a collection of
      insertion sequences were created and introduced into the artificial 5S rRNA
      cassette. This library consisted of random 13- and 50-base oligonucleotides that
      were inserted into the carrier RNA. We report here that essentially all of the
      insert-containing RNAs are stable and accumulate to detectable levels. Tagged
      RNAs were produced by both plasmid-borne and chromosomally integrated expression
      systems in E. coli and several Pseudomonas strains without obvious effect on the
      host cell. It is anticipated that in addition to its intended use in
      environmental monitoring, this system can be used for in vivo selection of useful
      artificial RNAs. Because the carrier lends stability to the RNAs, the system may
      also be useful in RNA production.

PMID- 12790634
TI  - Lipase-catalyzed synthesis of butyl butyrate by alcoholysis in an integrated
      liquid-vapor system.
AB  - This paper reports experimental work pertaining to alcoholysis between butanol
      and ethyl butanoate, catalyzed by an immobilized lipase in a liquid-vapor system
      where chemical reaction and physical separation are simultaneously carried out.
      The processing setup was tested for various compositions of the starting
      feedstock and operated under reduced pressure. Samples were withdrawn both from
      the boiler and the condenser, and they were chromatographically assayed for butyl
      butyrate. The integrated configuration tested is quite effective toward
      improvement of the final yield of the desired product.

PMID- 12790633
TI  - Effect of culture conditions on the degree of sialylation of a recombinant
      glycoprotein expressed in insect cells.
AB  - Secreted human placental alkaline phosphatase (SEAP) was produced in a
      nonengineered Trichoplusia ni insect cell line, Tn-4s, using a recombinant
      Autographa californica baculovirus expression vector. The effect of culture
      conditions on SEAP specific yield and glycosylation was studied. When cultured in
      the high aspect ratio vessel (HARV) or in tissue culture flasks (T-flasks),
      baculovirus-infected Tn-4s cells produced high levels of SEAP (13 and 23 U/10(6)
      cells, respectively; 4 days postinfection), but in those conditions SEAP
      possessed only high mannose, paucimannosidic, and hybrid structures. In spinner
      flasks, lower SEAP yields were obtained (<4 U/10(6) cells, 3 days postinfection),
      but in such cultures, sialylation of SEAP could be achieved. Several spinner
      flask culture conditions were tested and resulted in different SEAP specific
      yields and levels of sialylation. The highest level of sialylation (9%) was
      obtained in the culture with the lowest agitation rate and lowest yield (1.2
      U/10(6) cells), suggesting a limiting capacity of the Tn-4s cells to process
      glycoproteins to sialylation. High specific yield, low passage number Tn5B1-4
      cells did not produce SEAP with complex glycosylation when cultured in a low
      agitation rate spinner-flask. On the basis of these results, we propose that the
      Golgi apparatus has a limited capacity for processing proteins to complex
      glycosylation and sialylation and that this capacity is easily overwhelmed by
      high levels of foreign protein productivity. Selected media additives such as
      Pluronic F-68, dextran sulfate (MW 12 500) and a lipids premix did not allow
      improvement of the specific yield of sialylated SEAP when supplemented to spinner
      flask cultures.

PMID- 12790635
TI  - Auxiliary phase guidelines for microbial biotransformations of toxic substrate
      into toxic product.
AB  - When an industrial process is developed using the microbial transformation of a
      precursor into a desired chemical compound, high concentrations of substrate and
      product will be involved. These compounds may become toxic to the cells. In situ
      product removal (ISPR) may be carried out, using auxiliary phases such as
      extractants or adsorbents. Simultaneously, in situ substrate addition (ISSA) may
      be performed. It is shown that for uncharged substrates and products, the aqueous
      solubilities of substrate and product can be used to predict if ISPR might be
      required. When a particular auxiliary phase is selected and the distribution
      coefficients of substrate and product are known, it is possible to estimate a
      priori if this auxiliary phase might be good enough and how much of it might be
      needed for an efficient (fed-)batch biotransformation process. For
      biotransformation products of intermediate polarity (aqueous solubility of about
      1-10 g/L) there seems to be a lack of extractants and adsorbents with the
      capacity to raise the product concentrations to commercially more interesting
      levels.

PMID- 12790636
TI  - Preparation of a stable biocatalyst of bovine liver catalase using immobilization
      and postimmobilization techniques.
AB  - Bovine liver catalase was immobilized on different supports. The tetrameric
      nature of this enzyme was found to cause its rapid inactivation in diluted
      conditions due to subunit dissociation, a fact that may rule out its industrial
      use. Multi-subunit immobilization using highly activated glyoxyl agarose was not
      enough to involve all enzyme subunits. In fact, washing the derivative produced a
      strong decrease in the enzyme activity. Further cross-linking of previously
      immobilized enzyme with tailor-made dextran-aldehyde permitted the multimeric
      structure to be fully stabilized using either multisubunit preparations
      immobilized onto highly activated glyoxyl-agarose support or one subunit enzymes
      immobilized onto poorly activated glyoxyl-agarose. The highest stability of the
      final biocatalyst was observed using the multisubunit immobilized derivative
      cross-linked with dextran-aldehyde. The optimal derivative retained around 60% of
      the immobilized activity, did not release any enzyme subunits after boiling in
      the presence of SDS, and did not lose activity during washing, and its stability
      did not depend on the dilution. This derivative was used for 10 cycles in the
      destruction of 10 mM hydrogen peroxide without any decrease in the enzyme
      activity.

PMID- 12790637
TI  - Controlling substrate concentration in fed-batch candida magnoliae culture
      increases mannitol production.
AB  - Candida magnoliae HH-01, a yeast strain that is currently used for the industrial
      production of mannitol, has the highest mannitol production ever reported for a
      mannitol-producing microorganism. However, when the fructose concentration
      exceeds 150 g/L, the volumetric mannitol production rate decreases because of a
      lag in mannitol production, and the yield decreases as a result of the formation
      of side products. In fed-batch culture, the volumetric production rate and
      mannitol yield from fructose vary substantially with the fructose concentration
      and are maximal at a controlled fructose concentration of 50 g/L. In continuous
      feeding experiments, the maximum mannitol yield was 85% (g/g) at a
      glucose/fructose feeding ratio of 1/20. A high glucose concentration in the
      production phase resulted in the formation of ethanol followed by a decrease in
      yield and productivity. NAD(P)H-dependent mannitol dehydrogenase was purified to
      homogeneity from C. magnoliae. In vitro, mannitol dehydrogenase was inhibited by
      increasing ethanol concentration. Mannitol product was also found to be
      inhibitory with a K(i) of 183 mM. Under optimum conditions, a final mannitol
      production of 213 g/L was obtained from 250 g fructose/L after 110 h.

PMID- 12790638
TI  - Impact of low-temperature plasmas on Deinococcus radiodurans and biomolecules.
AB  - The effects of cold plasma on Deinococcus radiodurans, plasmid DNA, and model
      proteins were assessed using microbiological, spectrometric, and biochemical
      techniques. In low power O(2) plasma (approximately 25 W, approximately 45 mTorr,
      90 min), D. radiodurans, a radiation-resistant bacterium, showed a 99.999%
      reduction in bioburden. In higher power O(2) plasma (100 W and 500 mTorr), the
      reduction rate increased about 10-fold and observation by atomic force microscopy
      showed significant damage to the cell. Damage to cellular lipids, proteins, and
      chromosome was indicated by losses of infrared spectroscopic peaks at 2930, 1651,
      1538, and 1245 cm(-1), respectively. In vitro experiments show that O(2) plasmas
      induce DNA strand scissions and cross-linking as well as reduction of enzyme
      activity. The observed degradation and removal of biomolecules was power
      dependent. Exposures to 200 W at 500 mTorr removed biomolecules to below
      detection limits in 60 s. Emission spectroscopy indicated that D. radiodurans
      cells were volatilized into CO(2), CO, N(2), and H(2)O, confirming that these
      plasmas were removing complex biological matter from surfaces. A CO(2) plasma was
      not as effective as the O(2) plasma, indicating the importance of plasma
      composition and the dominant role of chemical degradation. Together, these
      findings have implications for NASA planetary protection schemes and for the
      contamination of Mars.

PMID- 12790639
TI  - Use of physicochemical tools to determine the choice of optimal enzyme:
      stabilization of D-amino acid oxidase.
AB  - An evaluation of the stability of several forms (including soluble and two
      immobilized preparations) of d-amino acid oxidases from Trigonopsis variabilis
      (TvDAAO) and Rhodotorula gracilis (RgDAAO) is presented here. Initially, both
      soluble enzymes become inactivated via subunit dissociation, and the most
      thermostable enzyme seemed to be TvDAAO, which was 3-4 times more stable than
      RgDAAO at a protein concentration of 30 microg/mL. Immobilization on poorly
      activated supports was unable to stabilize the enzyme, while highly activated
      supports improved the enzyme stability. Better results were obtained when using
      highly activated glyoxyl agarose supports than when glutaraldehyde was used.
      Thus, multisubunit immobilization on highly activated glyoxyl agarose
      dramatically improved the stability of RgDAAO (by ca. 15,000-fold) while only
      marginally improving the stability of TvDAAO (by 15-20-fold), at a protein
      concentration of 6.7 microg/mL. Therefore, the optimal immobilized RgDAAO was
      much more stable than the optimal immobilized TvDAAO at this enzyme
      concentration. The lower stabilization effect on TvDAAO was associated with the
      inactivation of this enzyme by FAD dissociation that was not prevented by
      immobilization. Finally, nonstabilized RgDAAO was marginally more stable in the
      presence of H(2)O(2) than TvDAAO, but after stabilization by multisubunit
      immobilization, its stability became 10 times higher than that of TvDAAO.
      Therefore, the most stable DAAO preparation and the optimal choice for an
      industrial application seems to be RgDAAO immobilized on glyoxyl agarose.

PMID- 12790640
TI  - Benzene transformation in nitrifying batch cultures.
AB  - The effect of benzene on the nitrifying activity of a sludge produced in steady
      state nitrification was evaluated in batch cultures. Benzene at 10 mg/L inhibited
      nitrate formation by 53%, whereas at 5 mg/L there was no inhibition. For initial
      benzene concentrations of 0, 7, and 10 mg/L, the specific rates of NO(3)(-)-N
      production were 0.545 +/- 0.101, 0.306 +/- 0.024, and 0.141 +/- 0.010 g NO(3)(-)
      N/g microbial protein-N.h, respectively. The specific rates of benzene
      consumption at 7, 12, and 20 mg/L were 0.034 +/- 0.003, 0.050 +/- 0.006, and
      0.027 +/- 0.002 g/g microbial protein-N.h, respectively. Up to a concentration of
      10 mg/L, benzene was first oxidized to phenol, which was later totally oxidized
      to acetate. Benzene at higher concentrations (20 and 30 mg/L) was converted to
      intermediates other than acetate, phenol, or catechol. These results suggest that
      this type of nitrifying consortium coupled with a denitrification system may have
      promising applications for complete removal of nitrogen and benzene from
      wastewaters.

PMID- 12790641
TI  - Improved production of recombinant ovine interferon-tau by mut(+) strain of
      Pichia pastoris using an optimized methanol feed profile.
AB  - Recombinant ovine interferon-tau (r-oIFN-tau) production by Pichia pastoris was
      studied using methanol as the sole carbon source during induction. The cells were
      grown on glycerol up to a certain cell density before induction of the AOX1
      promoter by methanol for expression of the recombinant protein. Cell growth on
      methanol has been modeled using a substrate-feed equation, which served as the
      basis for an effective computer control of the process. The r-oIFN-tau
      concentration in the culture began to decline despite continued cell growth after
      50 (+/- 6) h of induction, which was associated with an increase in proteolytic
      activity of the fermentation broth. A specific growth rate of 0.025 h(-1) was
      found to be optimal for r-oIFN-tau production. No significant improvement in r
      oIFN-tau production was observed when the specific growth rate was stepped up
      before the critical point when r-oIFN-tau concentration started decreasing during
      fermentation. However, best results were obtained when the specific growth rate
      was stepped down from 0.025 to 0.02 h(-1) at 38 h of induction, whereby the
      active production period was prolonged until 70 h of induction and the broth
      protease activity was correspondingly reduced. The corresponding maximum protein
      yield was 391.7 mg x L(-1) after 70 h of fermentation. The proteolytic activity
      could be reduced by performing fermentations at specific growth rates of 0.025 h(
      1) or below. The recombinant protein production can be performed at an optimal
      yield by directly controlling the methanol feed rate by a computer-controlled
      model. The production profile of r-oIFN-tau was found to be significantly
      different from other secreted and intracellular recombinant protein processes,
      which is an indication that recombinant protein production in Pichia pastoris
      needs to be optimized as individual processes following established principles.

PMID- 12790642
TI  - Covalent coupling method for lipase immobilization on controlled pore silica in
      the presence of nonenzymatic proteins.
AB  - Candida rugosa lipase was covalently immobilized on silanized controlled pore
      silica previously activated with glutaraldehyde in the presence of nonenzymatic
      proteins. This strategy is suggested to protect the enzyme from aggregation
      effects or denaturation that occurs as a result of the presence of silane
      precursors used in the formation of the silica matrix. The immobilization yield
      was evaluated as a function of the lipase loading and the additive type (albumin
      and lecithin) using statistical concepts. In agreement with the mathematical
      model, the maximum coupling yield (32.2%) can be achieved working at high lipase
      loading (450 units x g(-1) support) using albumin as an additive. In these
      conditions, the resulting immobilized lipase exhibits high hydrolytic (153.2 U x
      mg(-1)) and esterification (337.6 mmol x g(-1) x min) activities. The enhanced
      activity of the final lipase derivative is the sum of the benefits of the
      immobilization (that prevents enzyme aggregation) and the lipase coating by
      additives that increases the accessibility of active sites to the substrate.

PMID- 12790643
TI  - Phosphoenolpyruvate availability and the biosynthesis of shikimic acid.
AB  - The impact of increased availability of phosphoenolpyruvate during shikimic acid
      biosynthesis has been examined in Escherichia coli K-12 constructs carrying
      plasmid-localized aroF(FBR) and tktA inserts encoding, respectively, feedback
      insensitive 3-deoxy-d-arabino-heptulosonic acid 7-phosphate synthase and
      transketolase. Strategies for increasing the availability of phosphoenolpyruvate
      were based on amplified expression of E. coli ppsA-encoded phosphoenolpyruvate
      synthase or heterologous expression of the Zymomonas mobilis glf-encoded glucose
      facilitator. The highest titers and yields of shikimic acid biosynthesized from
      glucose in 1 L fermentor runs were achieved using E. coli SP1.lpts/pSC6.090B,
      which expressed both Z. mobilis glf-encoded glucose facilitator protein and Z.
      mobilis glk-encoded glucose kinase in a host deficient in the
      phosphoenolpyruvate:carbohydrate phosphotransferase system. At 10 L scale with
      yeast extract supplementation, E. coli SP1.lpts/pSC6.090B synthesized 87 g/L of
      shikimic acid in 36% (mol/mol) yield with a maximum productivity of 5.2 g/L/h for
      shikimic acid synthesized during the exponential phase of growth.

PMID- 12790644
TI  - Scale-up of a new bacterial mannitol production process.
AB  - D-Mannitol is a sugar alcohol with applications in chemistry, food and
      pharmaceutical industries, and medicine. Commercially, mannitol is produced by
      catalytic hydrogenation. Although this process is widely used, it is not optimal
      for mannitol production. New processes, including chemical, enzymatic, and
      microbial processes, are frequently developed and evaluated against the existing
      hydrogenation processes. In earlier papers, we have described the identification
      of a food-grade lactic acid bacterium strain, Leuconostoc mesenteroides ATCC
      9135, with efficient mannitol production capabilities and the development and
      optimization of a new bioprocess in which the strain was applied. The new
      bioprocess is simple. It requires a reduced bioreactor with the following
      features: sterilization, pH and T control (at mild conditions), and slow mixing.
      The contamination risk of the new bioprocess is low, and the downstream
      processing protocol comprises simple, widely used unit operations: evaporation,
      crystallization, crystal separation, and drying. On a 2-L laboratory scale, high
      mannitol yields from fructose (93-97%) and volumetric mannitol productivities
      (>20 g L(-1) h(-1)) were achieved. In this paper, the scalability of the new
      bioprocess was tested on a small pilot scale (100 L). In the pilot plant,
      production levels were achieved similar to those in the laboratory. Also, high
      purity mannitol crystals were obtained at similar yield levels. The results
      presented in this paper indicate that the new bioprocess can easily be scaled-up
      to an industrial scale and that the production levels achieved with it are
      comparable to the catalytic hydrogenation processes.

PMID- 12790645
TI  - Development of a phenomenological modeling approach for prediction of growth and
      xanthan gum production using Xanthomonas campestris.
AB  - An unstructured kinetic model for xanthan production is described and fitted to
      experimental data obtained in a stirred batch reactor. The culture medium was
      composed of several nitrogen sources (soybean hydrolysates, ammonium and nitrate
      salts) consumed sequentially. The model proposed is able to describe this
      sequential consumption of nitrogen sources, the consumption of inorganic
      phosphate and carbon, the evolution of biomass, and production of xanthan. The
      parameter estimation has been performed by fitting the kinetic model in
      differential form to experimental data. Runs of the model for simulating xanthan
      gum production as a function of the initial concentration of inorganic phosphate
      have shown the positive effect of phosphate limitation on xanthan yield, though
      diminishing rates of production. The model was used to predict the kinetic
      parameters for a medium containing a 2-fold lower initial phosphate
      concentration. When tested experimentally, the measured fermentation parameters
      were in close agreement with the predicted model values, demonstrating the
      validity of the model.

PMID- 12790646
TI  - Hydrogen production with immobilized sewage sludge in three-phase fluidized-bed
      bioreactors.
AB  - Municipal sewage sludge was immobilized with a modified alginate gel entrapment
      method, and the immobilized cells were used to produce hydrogen gas in a three
      phase fluidized bed. The hydrogen-producing fluidized beds were operated at
      different liquid velocity (U(0)) and hydraulic retention time (HRT). The results
      show that in response to operating liquid velocities, the fluidized-bed system
      had three flow regimes, namely, plug flow, slug flow, and free bubbling. Pressure
      fluctuation analysis was used to analyze the hydrodynamic properties in this
      three-phase fluidized bed when it was under a steady-state production of biogas.
      With a steady-state biogas production rate (U(g)) of 0.196 mL/s/L, a transition
      state occurred at a liquid velocity (U(0)) of 0.85 cm/s. As U(0) < 0.85 cm/s, the
      system was basically a nonhomogeneous fluidized bed, whereas the bed became
      homogeneous when U(0) was higher than 0.85 cm/s. The fluidized bed can be stably
      carried out at high loading rates (HRT as low as 2 h). Hydrogen fermentation
      results show that the maximal hydrogen production rate was 0.93 L/h/L and the
      best yield (Y(H)2(/sucrose)) was 2.67 mol H(2)/mol sucrose.

PMID- 12790647
TI  - Comparison of a production process in a membrane-aerated stirred tank and up to
      1000-L airlift bioreactors using BHK-21 cells and chemically defined protein-free
      medium.
AB  - The applicability of a protein-free medium for the production of recombinant
      human interleukin-2 with baby hamster kidney cells in airlift bioreactors was
      investigated. For this purpose, a BHK-21 cell line, adapted to grow and produce
      in protein-free SMIF7 medium without forming spheroids in membrane-aerated bubble
      free bioreactors, was used as the producer cell line. First, cultivation of the
      cells was established at a 20-L scale using an internal loop airlift bioreactor
      system. During the culturing process the medium formulation was optimized
      according to the specific requirements associated with cultivation of mammalian
      cells under protein-free conditions in a bubble-aerated system. The effects of
      the addition of an antifoam agent on growth, viability, productivity, metabolic
      rates, and release of lactate dehydrogenase were investigated. Although it was
      possible to establish cultivation and production at a 20-L scale without the use
      of antifoaming substances, the addition of 0.002% silicon-oil-based antifoaming
      reagent improved the cultivation system by completely preventing foam formation.
      This reduced the release of lactate dehydrogenase activity to the level found in
      bubble-free aerated stirred tank membrane bioreactors and led to a reduction in
      generation doubling times by about 5 h (17%). Using the optimized medium
      formulation, cells were cultivated at a 1000-L scale, resulting in a culture
      performance comparable to the 20-L airlift bioreactor. For comparison,
      cultivations with protein-containing SMIF7 medium were carried out at 20- and
      1000-L scales. The application of protein supplements did not lead to a
      significant improvement in the cultivation conditions. The results were also
      compared with experiments performed in a bubble-free aerated stirred tank
      membrane bioreactor to evaluate the influence of bubbles on the investigated
      culture parameters. The data implied a higher metabolic activity of the cells in
      airlift bioreactors with a 150% higher glucose consumption rate. The results of
      this study clearly demonstrate the applicability of a protein-free chemically
      defined medium for the production of recombinant proteins with BHK cells in
      airlift bioreactors.

PMID- 12790648
TI  - Naphthalene biodegradation from non-aqueous-phase liquids in batch and column
      systems: comparison of biokinetic rate coefficients.
AB  - The kinetics of microbial degradation of naphthalene from a two-component non
      aqueous-phase liquid (NAPL) coated onto uniformly sized nonporous particles were
      evaluated in a completely mixed batch reactor (CMBR) system and in flow-through
      column systems to examine the differences in the biodegradation kinetic
      coefficients, micro(max), the maximum specific growth rate coefficient, and K(s),
      the half saturation constant in the two systems. The values of these coefficients
      were estimated by nonlinear least-squares regression of the naphthalene
      mineralization profiles obtained from both CMBR and column biodegradation
      experiments. The results show that the range of values for micro(max) and K(s)
      obtained from column systems are very similar to the range of values obtained
      from CMBR systems. This suggests that coefficients estimated from CMBR or column
      systems are equally applicable for modeling studies. The presence of
      microorganisms and the development of biofilms at the NAPL-water interface
      reduced the mass transfer rates of naphthalene from the NAPL by 60% in CMBR and
      by 70% in column systems. If such changes in mass transfer coefficients are not
      accounted for, significantly erroneous values of biokinetic coefficients may be
      obtained.

PMID- 12790649
TI  - Use of co-immobilized beta-amylase and pullulanase in reduction of
      saccharification time of starch and increase in maltose yield.
AB  - Beta-amylase and pullulanase were co-immobilized to poly(acrylamide-acrylic acid)
      resin [P(AAm-AAc)] using 1-ethyl-3-(3-dimethylaminopropyl) carbodimide
      hydrochloride (EDC). The combined beta-amylase and pullulanase activity was 32%
      relative to the nonimmobilized beta-amylase. Co-immobilization of beta-amylase
      and pullulanase increased the maltose yield compared to thart of the immobilized
      beta-amylase alone and reduced the saccharification time to about 50 h. The
      results showed that there is a significant increase in the thermal stability, pH
      stability, and stability toward gamma irradiation. The results also suggest that
      the co-immobilization of beta-amylase and pullulanase is a potentially useful
      approach for commercial starch hydrolysis.

PMID- 12790650
TI  - Influence of hydrodynamic conditions on biofilm behavior in a methanogenic
      inverse turbulent bed reactor.
AB  - This paper presents a study about the influence of gas velocity on a methanogenic
      biofilm in an inverse turbulent bed reactor. Experimental results indicate a
      dynamic response of the growing attached biomass to the changes of hydrodynamic
      conditions, mainly attrition constraints. Short but intensive increases of gas
      velocity (U(g)) are shown to induce more detachment than a high but constant gas
      flow rate. Hydrodynamic conditions control the composition of the growing biofilm
      in terms of cells and exocellular polymeric substances (EPS). The cell fraction
      within the biofilm (R(cell)) was found to be inversely proportional to the gas
      velocity. The specific activity expressed in methane production rate or COD
      removal rate is higher in biofilms formed under high hydrodynamic constraints.
      The control of the hydrodynamic conditions in a biofilm reactor should make it
      possible to obtain a resistant and active biofilm.

PMID- 12790652
TI  - Microbial desizing using starch as model compound: enzyme properties and desizing
      efficiency.
AB  - A film of sizing agents protects yarn during weaving. Its removal in a subsequent
      washing process causes 50% of the organic effluent load of textile finishing
      processes and requires large amounts of auxiliary chemicals (e.g., surfactants).
      Microbial desizing is a new bioprocess that uses the acidifying culture of a two
      phase anaerobic digestion plant for the removal and partial degradation
      (acidification) of the sizing agent. Soluble starch is used in this study to
      characterize the enzymatic properties in the supernatant of the desizing culture
      and to link them to desizing efficiencies. The supernatant of the culture (grown
      at 37 degrees C, pH 5.5) displayed the highest enzymatic activity between pH 4
      and 5 and in a broad temperature range (20-80 degrees C). Highest metabolization
      rates were determined with the substrate amylose. Short chain dextrins (average
      of 5 and 10 glucose units) and amylopectin were converted significantly more
      slowly. At 37 degrees C the half-life time of the enzymatic activity in the
      supernatant was 45 h. In a desizing test a decisive reduction of the chain length
      was found already after 1 h (allowing starch solubilization). A microbial
      desizing experiment with dyed, native maize starch demonstrated the efficiency of
      the proposed bioprocess.

PMID- 12790651
TI  - Production, IMAC purification, and molecular modeling of N-carbamoyl-D-amino acid
      amidohydrolase C-terminally fused with a six-his peptide.
AB  - A six-His peptide was genetically engineered to the C-terminus of Agrobacterium
      radiobacter N-carbamoyl-D-amino acid amidohydrolase monomer to facilitate the
      protein purification with immobilized metal affinity chromatography (IMAC). The
      fusion enzyme, named as DCaseH, was overexpressed in Escherichia coli and one
      step IMAC-purified. The production study showed that DCaseH was optimally
      produced at 15 degrees C for 25 h by the induction of 0.05 mM IPTG. Both Co(2+)
      chelated TANOL gels and Ni(2+)-chelated nitriloacetic acid agarose gels
      efficiently purified DCaseH, with the former yielding purer enzyme than the
      latter. Highly pure DCaseH was obtained in the former purification with the
      addition of 5 mM imidazole in the washing buffer, and the specific enzyme
      activity was increased more than 11-fold. Denaturing IMAC purification
      successfully purified DCaseH from inclusion bodies that were mostly composed of
      the overexpressed DCaseH, while the attempt to refold the purified enzyme by
      either dialysis or solid-state refolding was not achieved. The purified native
      enzyme was optimally active at pH 6.5 and 50 degrees C, and the presence of 10%
      glycerol increased the activity. The molecular modeling of dimeric DCaseH
      indicated that the six-His tags were freely exposed to the protein surface,
      resulting in the selective and effective IMAC purification of DCaseH.

PMID- 12790653
TI  - Expanded bed adsorption of protein with DEAE Spherodex M.
AB  - In this article, the bed expansion behavior and the hydrodynamic and protein
      adsorption properties of the DEAE Spherodex M in expanded bed with mobile phases
      of different viscosities have been studied. The axial liquid-phase dispersion
      coefficient is found to be on the order of 10(-6) m(2)/s, falling into the common
      range from 1.0 x 10(-6) to 1.0 x 10(-5) m(2)/s observed previously in expanded
      bed operation. Because of the small size of the adsorbent, the high pore
      diffusivity of protein and the favorable column efficiency (low dispersion
      coefficient), the dynamic binding capacity (DBC) of bovine serum albumin (BSA) at
      5% breakthrough in the expanded bed reaches over 80% that of the equilibrium
      adsorption density (EAD). Moreover, a theoretical model with unadjustable model
      parameters is used for the prediction of the breakthrough curves. Computer
      simulations show that the model agrees well with the experimental results at
      breakthrough less than about 50%. It indicates that the model is promising in the
      prediction of protein breakthrough behavior because breakthrough profiles at 5
      50% breakthrough points are more important in practical applications.

PMID- 12790654
TI  - Efficient inclusion body processing using chemical extraction and high gradient
      magnetic fishing.
AB  - In this study we introduce a radical new approach for the recovery of proteins
      expressed in the form of inclusion bodies, involving (i) chemical extraction from
      the host cells, (ii) adsorptive capture of the target protein onto small magnetic
      adsorbents, and (iii) subsequent rapid collection of the product-loaded supports
      with the aid of high gradient magnetic fields. The manufacture and testing of two
      types of micron-sized nonporous superparamagnetic metal chelator particles
      derivatized with iminodiacetic acid is described. In small-scale adsorption
      studies conducted with a hexahistidine tagged form of the L1 coat protein of
      human papillomavirus type 16 dissolved in 8 M urea-phosphate buffer, the best
      binding performance (Q(max) = 58 mg g(-1) and K(d) approximately 0.08 microM) was
      exhibited by Cu(2+)-charged type II support materials. Equilibrium adsorption of
      L1 to these nonporous supports was achieved very rapidly (<300 s), and
      approximately 90% of the tightly bound L1 could be desorbed in just one elution
      step by including >100 mM imidazole in the equilibration buffer. The influence of
      feedstock complexity on L1 adsorption to the Cu(2+)-charged type II magnetic
      chelators was studied using various dilutions of four crude chemical E. coli cell
      extracts containing denatured L1 protein. Undiminished L1 adsorption to these
      adsorbents (relative to the 8 M urea-phosphate buffer case) was observed with the
      least complex of these feed materials, i.e., a partially clarified (12 g dry
      weight L(-1)) and spermine-treated chemical cell extract (feedstock B). Efficient
      recovery of L1 from feed B was demonstrated at a 60-fold increased scale using
      the high gradient magnetic fishing (HGMF) system to collect loaded Cu(2+)
      chelator particles following batch adsorption of L1. Over 70% of the initial L1
      present was recovered within the HGMF rig in a highly clarified form in two batch
      elution cycles with an overall purification factor of approximately 10.

PMID- 12790655
TI  - Magnetophoretic cell sorting is a function of antibody binding capacity.
AB  - Antibody binding capacity (ABC) is a term representing a cell's ability to bind
      antibodies, correlating with the number of specific cellular antigens expressed
      on that cell. ABC allows magnetically conjugated antibodies to bind to the
      targeted cells, imparting a magnetophoretic mobility on each targeted cell. This
      enables sorting based on differences in the cell magnetophoretic mobility and,
      potentially, a magnetic separation based on the differences in the cell ABC
      values. A cell's ABC value is a particularly important factor in continuous
      magnetic cell separation. This work investigates the relationship between ABC and
      magnetic cell separation efficiency by injection of a suspension of
      immunomagnetically labeled quantum simply cellular calibration microbeads of
      known ABC values into fluid flowing through a quadrupole magnetic sorter. The
      elution profiles of the outlet streams were evaluated using UV detectors. Optimal
      separation flow rate was shown to correlate with the ABC of these microbeads.
      Comparing experimental and theoretical results, the theory correctly predicted
      maximum separation flow rates but overestimated the separation fractional
      recoveries.

PMID- 12790656
TI  - High-pressure processing of apple juice: kinetics of pectin methyl esterase
      inactivation.
AB  - High-pressure (HP) inactivation kinetics of pectin methyl esterase (PME) in apple
      juice were evaluated. Commercial PME was dispensed in clarified apple juice,
      sealed in dual peel sterilizable plastic bags, and subjected to different high
      pressure processing conditions (200-400 MPa, 0-180 min). Residual enzyme activity
      was determined by a titration method estimating the rate of free carboxyl group
      released by the enzyme acting on pectin substrate at pH 7.5 (30 degrees C). The
      effects of pressure level and pressure holding time on enzyme inactivation were
      significant (p < 0.05). PME from the microbial source was found to be more
      resistant (p < 0.05) to pressure inactivation than PME from the orange peel.
      Almost a full decimal reduction in the activity of commercial PME was achieved by
      HP treatment at 400 MPa for 25 min. Inactivation kinetics were evaluated on the
      basis of a dual effect model involving a pressure pulse effect and a first-order
      rate model, and the pressure sensitivity of rate constants was modeled by using
      the z-value concept.

PMID- 12790657
TI  - On-column refolding of recombinant human interferon-gamma with an immobilized
      chaperone fragment.
AB  - The chaperone mini-GroEL is a soluble recombinant fragment containing the 191-345
      amino acid sequence of GroEL with a 6xHis tag. The refolding protocol assisted
      with mini-GroEL was studied for the activity recovery of rhIFN-gamma inclusion
      bodies. In a suspended system, mini-GroEL showed significant enhancement of the
      activity recovery of rhIFN-gamma, applyed with a 1-5:1 stoichiometry of mini
      GroEL to rhIFN-gamma at 25 degrees C. Moreover, 1 M urea in the renaturation
      buffer had a synergistic effect on suppressing the aggregation and improving the
      activity recovery. Finally, a novel chromatographic column, containing 1 cm
      height of Sephadex G 200 at the top of column and packed with immobilized mini
      GroEL to promote refolding, was devised. The total activity recovered per
      milligram of denatured rhIFN-gamma was up to 3.93 x 10(6) IU with the immobilized
      mini-GroEL column, which was reused four times without evident loss of
      renaturation ability. A convenient technique with the integrated process of
      chaperon preparation and rhIFN-gamma folding in vitro was developed.

PMID- 12790658
TI  - Use of ceramic monoliths as stationary phase in affinity chromatography.
AB  - The use of coated ceramic monoliths as support for affinity chromatography is
      described. Ceramic monoliths are robust active matrix supports and present a very
      small pressure drop. Monoliths are coated with a very thin agarose gel layer and
      activated using a standard activation process for agarose beads. Experiments
      demonstrate that enzyme adsorption occurs exclusively on the outside surface of
      the agarose coating since enzyme molecules are too large to fit into the porous
      matrix. Adsorption and desorption rates are large and production of enzyme per
      unit monolith volume justifies further exploring this separation process for
      large throughput operation.

PMID- 12790659
TI  - Reverse micellar extraction and precipitation of lysozyme using sodium di(2
      ethylhexyl) sulfosuccinate.
AB  - Sodium di(2-ethylhexyl) sulfosuccinate, referred to as Aerosol-OT or AOT, was
      used to remove lysozyme from an aqueous phase via reverse micellar extraction and
      precipitation method. For both methods, when the surfactant was in excess, a
      complete removal of lysozyme from the aqueous phase was obtained at the values of
      pH below the pI of lysozyme. However, for the reverse micellar method, a
      solubilization limit of lysozyme in the organic phase was observed, and a white
      precipitate was formed at the aqueous-organic interface. This observation
      suggested using AOT directly as a precipitating ligand. The lysozyme precipitated
      with AOT was fully recovered, with its original enzymatic activity, using acetone
      as a recovery solvent. A mechanism is suggested to explain the solubilization of
      lysozyme in an AOT reverse micellar system. It is shown that a direct
      precipitation method can be used with advantage instead of using the reverse
      micellar extraction method to recover lysozyme from an aqueous phase.

PMID- 12790660
TI  - Purification and kinetics of a raw starch-hydrolyzing, thermostable, and neutral
      glucoamylase of the thermophilic mold Thermomucor indicae-seudaticae.
AB  - The purified glucoamylase of the thermophilic mold Thermomucor indicae
      seudaticaehad a molecular mass of 42 kDa with a pI of 8.2. It is a glycoprotein
      with 9-10.5% carbohydrate content, which acted optimally at 60 degrees C and pH
      7.0, with a t(1/2) of 12 h at 60 degrees C and 7 h at 80 degrees C. Its
      experimental activation energy was 43 KJ mol(-1) with temperature quotient
      (Q(10)) of 1.35, while the values predicted by response surface methodology (RSM)
      were 43 KJ mol(-1) and 1.28, respectively. The enzyme hydrolyzed soluble starch
      at 50 degrees C (K(m) 0.50 mg mL(-1) and V(max) 109 micromol mg(-1) protein min(
      1)) and at 60 degrees C (K(m) 0.40 and V(max) 143 micromol mg(-1) protein min(
      1)). The experimental K(m) and V(max) values are in agreement with the predicted
      values at 50 degrees C (K(m) 0.45 mg mL(-1) and V(max) 111.11 micromol mg(-1)
      protein min(-1)) and at 60 degrees C (K(m) 0.36 mg mL(-1)and V(max) 142.85
      micromol mg(-1) protein min(-1)). An Arrhenius plot indicated thermal activation
      up to 60 degrees C, and thereafter, inactivation. The enzyme was strongly
      stimulated by Co(2+), Fe(2+), Ag(2+), and Ca(2+), slightly stimulated by Cu(2+)
      and Mg(2+), and inhibited by Hg(2+), Zn(2+), Ni(2+), and Mn(2+). Among additives,
      dextran and trehalose slightly enhanced the activity. Glucoamylase activity was
      inhibited by EDTA, beta-mercaptoethanol, dithiothreitol, and n-bromosuccinimide,
      and n-ethylmaleimide inhibited its activity completely. This suggested the
      involvement of tryptophan and cysteine in catalytic activity and the critical
      role of disulfide linkages in maintaining the conformation of the enzyme. The
      enzyme hydrolyzed around 82% of soluble starch and 65% of raw starch (K(m) 2.4 mg
      mL(-1), V(max) 50 micromol mg(-1) protein min(-1)), and it was remarkably
      insensitive to glucose, suggesting its applicability in starch saccharification.

PMID- 12790661
TI  - Prediction of band profiles of mixtures of bradykinin and kallidin from data
      acquired by competitive frontal analysis.
AB  - The competitive adsorption isotherms of two closely related peptides, bradykinin
      and kallidin, were measured by frontal analysis on a Zorbax SB-C18 microbore
      column. An aqueous soluton at 20% acetonitrile (0.1% TFA) was used as the mobile
      phase. The competitive isotherm data were fitted to four different models:
      Langmuir, Bilangmuir, Langmuir-Freundlich, and Toth. These data fitted best to a
      Bilangmuir isotherm model. The influence of the pressure on the retention factors
      of the two peptides was found to be small and was not investigated in detail. The
      band profiles of large samples of the single components and of their mixtures
      were recorded. The overloaded profiles calculated using either the equilibrium
      dispersive or POR model are in excellent agreement with the experimental profiles
      in all cases. Our results confirm that the competitive isotherm data derived from
      mixtures may suffice for a reasonably accurate prediction of the band profiles of
      all mixtures of the two components, provided their composition is close to 1/1.

PMID- 12790662
TI  - Parsing the effects of binding, signaling, and trafficking on the mitogenic
      potencies of granulocyte colony-stimulating factor analogues.
AB  - The pharmacodynamic potency of a therapeutic cytokine interacting with a cell
      surface receptor can be attributed primarily to three central properties: [1]
      cytokine/receptor binding affinity, [2] cytokine/receptor endocytic trafficking
      dynamics, and [3] cytokine/receptor signaling. Thus, engineering novel or second
      generation cytokines requires an understanding of the contribution of each of
      these to the overall cell response. We describe here an efficient method toward
      this goal in demonstrated application to the clinically important cytokine
      granulocyte colony-stimulating factor (GCSF) with a chemical analogue and a
      number of genetic mutants. Using a combination of simple receptor-binding and
      dose-response proliferation assays we construct an appropriately scaled plot of
      relative mitogenic potency versus ligand concentration normalized by binding
      affinity. Analysis of binding and proliferation data in this manner conveniently
      indicates which of the cytokine properties-binding, trafficking, and/or signaling
      are contributing substantially to altered potency effects. For the GCSF analogues
      studied here, two point mutations as well as a poly(ethylene glycol) chemical
      conjugate were found to have increased potencies despite comparable or slightly
      lower affinities, and trafficking was predicted to be the responsible mechanism.
      A third point mutant exhibiting comparable binding affinity but reduced potency
      was predicted to have largely unchanged trafficking properties. Surprisingly,
      another mutant possessing an order-of-magnitude weaker binding affinity displayed
      enhanced potency, and increased ligand half-life was predicted to be responsible
      for this net beneficial effect. Each of these predictions was successfully
      demonstrated by subsequent measurements of depletion of these five analogues from
      cell culture medium. Thus, for the GCSF system we find that ligand trafficking
      dynamics can play a major role in regulating mitogenic potency. Our results
      demonstrate that cytokine analogues can exhibit pharmacodynamic behaviors across
      a diverse spectrum of "binding-potency space" and that our analysis through
      normalization can efficiently elucidate hypotheses for the underlying mechanisms
      for further dedicated testing. We have also extended the Black-Leff model of
      pharmacological agonism to include trafficking effects along with binding and
      signaling, and this model provides a framework for parsing the effects of these
      factors on pharmacodynamic potency.

PMID- 12790663
TI  - Direct current electrical field effects on intact plant organs.
AB  - Intact plant tissues (of hypocotyls, radicles, cotyledons and leaves) were
      contracted by applying a low DC electrical field through them. Stomatal opening
      as a result of the electrical treatment of leaves was observed, presumably due to
      the differential influence of the electrical treatment on guard cell turgor
      pressure versus turgor pressure of the surrounding epidermal cells. In addition,
      leakage of minerals from the treated leaves was detected (higher contents of
      potassium, sodium, calcium and sulfur), as was leakage of betanin from
      electrically treated red beet roots (higher OD value of the immersion solution
      with increasing time of applied electrical field). Application of such a
      treatment can be used for initial drying or as part of another more drastic
      drying method. The advantages of this method lie in its nonthermal character and
      its potential to increase the quality of processed foods by maintaining their
      "like-fresh" quality, e.g., fruits and vegetables that are less damaged by
      browning. An understanding of the mechanism involved in this nonthermal
      application can help in controlling the process and predicting its outcome.

PMID- 12790664
TI  - Modeling of the co-transport of cryoprotective agents in a porous medium as a
      model tissue.
AB  - Cryopreservation is likely the choice for long-term preservation of natural and
      engineered tissues, and high concentration multiple cryoprotective agents (CPAs)
      are usually used in such a process. To achieve high cell viability after
      cryopreservation, cells at all locations within the tissue must be protected
      properly by the CPAs during freezing. It is hence essential to know the
      distribution and concentration of CPAs within the tissue during multiple-CPA
      addition, to maximize cell survival and minimize tissue damage. In this work, a
      model to describe the CPA transport during multiple-CPA addition in a one
      dimensional porous medium, as a simplified model of living tissue, was developed
      on the basis of the Maxwell-Stefan (M-S) equations. The UNIFAC and UNIQUAC models
      were used to evaluate the activity coefficients, and the Siddiqi-Lucas
      correlation was used for estimation of Maxwell-Stefan diffusivities. Simulations
      were carried out to examine the effect of temperature, tissue property, CPA type
      and the interactions between solutes on the CPA transport within construct during
      the CPA addition. It was found that these parameters, especially the interactions
      between the different CPA molecules, which was neglected before, significantly
      affect the transport of each individual CPA component. It is hence concluded that
      the traditional single-component analysis on the CPA diffusion is not adequate to
      quantify the multiple-CPA distribution in the tissue, particularly when the CPA
      concentrations are relatively high.

PMID- 12790665
TI  - Nucleic acid separations utilizing immobilized metal affinity chromatography.
AB  - Immobilized metal affinity chromatography (IMAC) is widely used for protein
      purification, e.g., in the isolation of proteins bearing the well-known
      hexahistidine affinity tag. We report that IMAC matrixes can also adsorb single
      stranded nucleic acids through metal ion interactions with aromatic base
      nitrogens and propose that metal affinity technologies may find widespread
      application in nucleic acid technology. Oligonucleotide duplexes, plasmid, and
      genomic DNA show low IMAC binding affinity, while RNA and single-stranded
      oligonucleotides bind strongly to matrixes such as Cu(II) iminodiacetic acid
      (IDA) agarose. The affinity of yeast RNA for IDA-chelated metal ions decreases in
      the following order: Cu(II), Ni(II), Zn(II), and Co(II). Adsorption isotherms for
      20-mer oligonucleotide homopolymers show that purines are strongly favored over
      pyrimidines and that double-stranded duplexes are not bound. IMAC columns have
      been used to purify plasmid DNA from E. coli alkaline lysates, to purify a
      ribozyme, to remove primers and imperfect products from PCR reactions, and to
      separate 20-mer oligonucleotide duplexes containing centered single-base
      mismatches. Potential further applications include SNP scoring, hybridization
      assays, and the isolation of polyadenylated messenger RNA.

PMID- 12790666
TI  - Quartz crystal microbalance study of endothelial cell number dependent
      differences in initial adhesion and steady-state behavior: evidence for cell-cell
      cooperativity in initial adhesion and spreading.
AB  - The quartz crystal microbalance (QCM) technique has been applied to the real time
      monitoring of endothelial cell (EC) adhesion and spreading on the QCM gold
      surface. We previously showed that the measured QCM Deltaf and DeltaR shifts were
      due to cells adhering to the gold crystal surface, requiring proteolytic enzyme
      treatment to be removed from the surface, in order for the Deltaf and DeltaR
      shifts to return to zero. In the present report, we demonstrate the quantitative
      dependence and saturation of the measured Deltaf and DeltaR shifts on the number
      of firmly attached ECs as measured by electronic counting of the cells. We
      demonstrate through a light microscope simulation experiment that the different
      Deltaf and DeltaR regions of the QCM temporal response curve correspond to the
      incident ECs contacting the surface, followed by their adhesion and spreading,
      which reflect cellular mass distribution and cytoskeletal viscoelasticity
      changes. Also, we demonstrate that the dose response curve of Deltaf and DeltaR
      values versus attached EC number is more sensitive and possesses less scatter for
      the hydrophilically treated surface compared to the native gold surface of the
      QCM. For both surfaces, a Deltaf and DeltaR versus trypsinized, attached EC
      number plot 1 h post-seeding exhibits a sigmoid curve shape whereas a similar
      plot 24 h post-seeding exhibits a hyperbolic curve shape. This number dependence
      suggests cell-cell cooperativity in the initial cell adhesion and spreading
      processes. These QCM data and our interpretation are corroborated by differences
      in cell appearance and spreading behavior we observed for ECs in a light
      microscope fluorescence simulation experiment of the cell density effect. For a
      stably attached EC monolayer at 24 h post-addition, steady-state Deltaf and
      DeltaR values are higher and exhibit saturation behavior for both the
      hydrophilically treated gold surface as compared to the untreated surface. The
      steady-state 24 h Deltaf and DeltaR values of stably attached ECs are shifted
      from the 1 h attached ECs. The 24 h values are characteristic of a more energy
      dissipative structure. This is consistent with the time-dependent elaboration of
      surface contacts in anchorage-dependent ECs via the attachment of intregrins to
      underlying extracellular matrix. It is also in agreement with the known energy
      dissipation function of the ECs that cover the interior of blood vessels and are
      exposed to continuous pulsatile blood flow.

PMID- 12790667
TI  - On-line monitoring of cell growth and cytotoxicity using electric cell-substrate
      impedance sensing (ECIS).
AB  - An on-line and continuous technique based on electric cell-substrate impedance
      sensing (ECIS) was developed for measuring the concentration and time response
      function of fibroblastic V79 cells exposed to mercury chloride and 1,3,5
      trinitrobenzene (TNB). Attachment, spreading and proliferation of V79
      fibroblastic cells cultured on a microarray of small gold electrodes precoated
      with fibronectin were detected as resistance changes. The response function was
      derived to reflect the resistance change as a result of cell attachment,
      spreading, mitosis and cytotoxicity effect. Exposure of V79 cells to mercury
      chloride or TNB led to alterations in cell behavior, and therefore, chemical
      cytotoxicity was easily screened by measuring the response function of the
      attached and spread cells in the presence of inhibitor. The half inhibition
      concentration, the required concentration to achieve 50% inhibition, was obtained
      from the response function to provide information about cytotoxicity during the
      course of the assay. A simple mathematical model was developed to describe the
      responses of ECIS that were related to the attachment, spreading, and
      proliferation of V79 fibroblastic cells. The novel results of this paper are
      mainly characterized by the systematic study of several parameters including the
      cell number, detection limit, sensor sensitivity, and cytotoxicity, and they may
      motivate further research and study of ECIS sensors.

PMID- 12790668
TI  - Measuring protein interactions by microchip self-interaction chromatography.
AB  - The self-interaction of proteins is of paramount importance in aggregation and
      crystallization phenomena. Solution conditions leading to a change in the state
      of aggregation of a protein, whether amorphous or crystalline, have mainly been
      discovered by the use of trial and error screening of large numbers of solutions.
      Self-interaction chromatography has the potential to provide a quantitative
      method for determination of protein self-interactions amenable to high-throughput
      screening. This paper describes the construction and characterization of a
      microchip separation system for low-pressure self-interaction chromatography
      using lysozyme as a model protein. The retention time was analyzed as a function
      of mobile-phase composition, amount of protein injected, flow rate, and
      stationary-phase modification. The capacity factors (k') as a function of
      crystallizing agent concentration are compared with previously published values
      for the osmotic second virial coefficient (B(22)) obtained by static light
      scattering, showing the ability of the chip to accurately determine protein
      protein interactions. A 500-fold reduction in protein consumption and the
      possibility of using conventional instrumentation and automation are some of the
      advantages over currently used methodologies for evaluating protein-protein
      interactions.

PMID- 12790670
TI  - Kinetic study on the enzymatic resolution of homophenylalanine ester using ionic
      liquids.
AB  - Two ionic liquids (ILs) were investigated as novel media for the enzymatic
      resolution of amino acid ester to obtain enantiomeric amino acid
      homophenylalanine. The effects of solvent nature, polarity, and concentration on
      the kinetic resolution were investigated. With change in solvent concentration, a
      systematic study shows that an improved enzyme activity can be obtained by
      adjusting these solvent parameters.

PMID- 12790669
TI  - Discovery of differentially expressed genes related to histological subtype of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human malignancies in
      the world. To identify the histological subtype-specific genes of HCC, we
      analyzed the gene expression profile of 10 HCC patients by means of cDNA
      microarray. We proposed a systematic approach for determining the discriminatory
      genes and revealing the biological phenomena of HCC with cDNA microarray data.
      First, normalization of cDNA microarray data was performed to reduce or minimize
      systematic variations. On the basis of the suitably normalized data, we
      identified specific genes involved in histological subtype of HCC. Two
      classification methods, Fisher's discriminant analysis (FDA) and support vector
      machine (SVM), were used to evaluate the reliability of the selected genes and
      discriminate the histological subtypes of HCC. This study may provide a clue for
      the needs of different chemotherapy and the reason for heterogeneity of the
      clinical responses according to histological subtypes.

PMID- 12790671
TI  - Nitrate removal in aquariums by immobilized pseudomonas.
AB  - Biological denitrification of nitrate to nitrogen gas was examined in a
      freshwater and a marine aquarium. Nitrate removal in the aquarium water was
      accomplished with denitrifiers immobilized in a freeze-dried, alginate-starch
      matrix. Starch served as a bacterial carbon source and cellular matrix
      strengthening filler. Freeze-dried beads were placed in canisters through which
      nitrate-rich aquarium water was recirculated. The freshwater aquarium (100 L)
      contained goldfish (Carassius auratus) at a total biomass of 390 g, whereas
      cichlids (Oreochromis mossambicus) were kept at a similar stocking density in the
      marine aquarium. Denitrification resulted in low ambient nitrate concentrations
      in both aquariums. The specific nitrate removal rate of the freshwater beads was
      significantly higher (50 microg of NO(3)-N/bead/day) than that of seawater beads
      (5 microg of NO(3)-N/bead/day). Differences in ambient nitrate concentrations
      between both aquariums and diffusion limitation of nitrate to the active
      denitrification sites within the beads might explain these observed differences.

PMID- 12790672
TI  - Vibration analysis on incubating eggs and its relation to embryonic development.
AB  - Coucke (1998) was the first to use acoustic resonance analysis to monitor embryo
      development in chicken eggs. He remarked that at around 100 hours of incubation,
      the course of the resonant frequency and damping changed abruptly in the case of
      fertile eggs. He also showed that these changes were related to a physiologic
      event during early embryonic development. The objective of our study is to
      monitor the course of the vibration parameters during the early incubation of
      chicken eggs and to relate these changes to egg and embryo characteristics. A
      total of 72 Hybro eggs were incubated vertically in a small incubator at standard
      conditions. Several egg parameters were measured before incubation. During the
      early stages of incubation the vibration behavior of these eggs was monitored.
      The time at which the damping of the vibration suddenly changed, the diameter of
      the eggs and their interaction were found to be significant explanatory variables
      in order to predict hatching time. A correlation coefficient r of 0.72 was
      obtained.

PMID- 12790673
TI  - Enhanced production of podophyllotoxin by Podophyllum hexandrum using in situ
      cell retention bioreactor.
AB  - The rhizomes of the rare plant Podophyllum hexandrum contain podophyllotoxin,
      which is a precursor of the anticancer drugs etoposide and teniposide. Batch
      cultivation of Podophyllum hexandrum was conducted using optimized medium in a 3
      L bioreactor, which resulted in biomass and podophyllotoxin concentrations of
      21.4 g/L and 13.8 mg/L in 24 and 26 days, respectively. The batch kinetics was
      used to identify the mathematical model. The model was extrapolated to identify
      the nutrient feeding rate (150 mL/d) and substrate concentration (105 g/L) in the
      incoming feed for nonlimiting and noninhibitory glucose concentration in the cell
      retention bioreactor. An improvement in cell growth to 53 g/L and intracellular
      podophyllotoxin accumulation of 48.8 mg/L was achieved in 60 days, when the
      bioreactor was operated in continuous cell retention cultivation mode.

PMID- 12790674
TI  - Use of salt hydrate pairs to control water activity for enzyme catalysis in ionic
      liquids.
AB  - Salt hydrate pairs were used to control water activity in the ionic liquid 1
      butyl-3-methylimidazolium hexafluorophosphate. It was shown that salt hydrate
      pairs behave essentially the same in ionic liquids as they do in organic solvents
      as long as they do not dissolve. Initial rate-water activity profiles were
      prepared for the immobilized Candida antarctica lipase catalyzed synthesis of 2
      ethylhexyl methacrylate. The ability to use salt hydrate pairs for the control of
      water activity in ionic liquids should allow for improved comparison of enzyme
      activity and specificity in ionic liquids and conventional solvents.

PMID- 12790675
TI  - Rolling adhesion kinematics of yeast engineered to express selectins.
AB  - Selectins are cell adhesion molecules that mediate capture of leukocytes on
      vascular endothelium as an essential component of the inflammatory response. Here
      we describe a method for yeast surface display of selectins, together with a
      functional assay that measures rolling adhesion of selectin-expressing yeast on a
      ligand-coated surface. E-selectin-expressing yeast roll specifically on surfaces
      bearing sialyl-Lewis-x ligands. Observation of yeast rolling dynamics at various
      stages of their life cycle indicates that the kinematics of yeast motion depends
      on the ratio of the bud radius to the parent radius (B/P). Large-budded yeast
      "walk" across the surface, alternately pivoting about bud and parent. Small
      budded yeast "wobble" across the surface, with bud pivoting about parent.
      Tracking the bud location of budding yeast allows measurement of the angular
      velocity of the yeast particle. Comparison of translational and angular
      velocities of budding yeast demonstrates that selectin-expressing cells are
      rolling rather than slipping across ligand-coated surfaces.

PMID- 12790676
TI  - Ultrasound increases the rate of bacterial cell growth.
AB  - Ultrasound was employed to increase the growth rate of bacterial cells attached
      to surfaces. Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia
      coli cells adhered to and grew on a polyethylene surface in the presence of
      ultrasound. It was found that low-frequency ultrasound (70 kHz) of low acoustic
      intensity (<2 W/cm(2)) increased the growth rate of the cells compared to growth
      without ultrasound. However, at high intensity levels, cells were partially
      removed from the surface. Ultrasound also enhanced planktonic growth of S.
      epidermidis and other planktonic bacteria. It is hypothesized that ultrasound
      increases the rate of transport of oxygen and nutrients to the cells and
      increases the rate of transport of waste products away from the cells, thus
      enhancing their growth.

PMID- 12790677
TI  - Comparison of fluidized bed and ultrasonic cell-retention systems for high cell
      density mammalian cell culture.
AB  - Economically viable biopharmaceutical production is to a high degree dependent on
      high product yields and stable fermentation systems that are easy to handle. In
      the current study we have compared two different fermentation systems for the
      production of recombinant protein from CHO cells. Both systems are fully
      scaleable and can be used for industrial high cell density bioprocesses. As a
      model cell line we have used a recombinant CHO cell line producing the enzyme
      arylsulfatase B (ASB). CHO cells were cultivated as adherent cell culture
      attached on Cytoline macroporous microcarrier (Amersham Biosciences, Sweden)
      using a Cytopilot Mini fluidized bed bioreactor (FBR, Vogelbusch-Amersham
      Biosciences, Austria) and as suspension culture using a stirred tank bioreactor
      equipped with a BioSep ultrasonic resonator based cell separation device
      (Applikon, The Netherlands). Both systems are equally well-suited for stable,
      long-term high cell density perfusion cell culture and provide industrial
      scalability and high yields. For products such as the recombinant ASB, high
      perfusion rates and therefore short product bioreactor residence times may be of
      additional benefit.

PMID- 12790678
TI  - Surface hydrophobicity of Aspergillus nidulans conidiospores and its role in
      pellet formation.
AB  - Formation of pellets by Aspergillus nidulans is primarily due to agglomeration of
      the fungal conidiospores. Although agglomeration of conidiospores has been known
      for a long time, its mechanism has not been clearly elucidated. To study the
      influence of the fungal conidiospore wall hydrophobicity on conidiospore
      agglomeration, pellet formation of an A. nidulans wild type and strains deleted
      in the conidiospore-wall-associated hydrophobins DewA and RodA was compared at
      different pH values. From contact angle measurements, RodA was found to be more
      important for the surface hydrophobicity than DewA. The absence of either
      hydrophobin led to a decrease in the relative amount of biomass present as
      pellets at all pH values as well as a decrease in the average size of the
      pellets. For all strains, an increasing alkalinity of the medium resulted in an
      increased pellet formation. Together with measurements of electrophoretic
      mobility, it is concluded that both the electrical charge and hydrophobicity of
      the conidiospores affects the pellet formation but that the conidiospore
      agglomeration process cannot be ascribed to these factors alone.

PMID- 12790679
TI  - Biosorption of milk substrates onto anaerobic flocculent and granular sludge.
AB  - Experiments were performed for adsorption of milk-based substrates onto anaerobic
      biomass at 35 degrees C. The influence of two parameters was studied, namely, the
      type of biomass (flocculent or granular) and the sludge adaptation to the
      substrate. It was found that flocculent sludge presented an adsorption capacity
      roughly 3 times higher than that of granular sludge. The adsorption data fit well
      with the Freundlich and Langmuir isotherms. Apparently, short-term sludge
      adaptation is not influential on the adsorption behavior. On the other hand, long
      term adapted sludge showed a higher adsorption capacity than nonadapted sludge,
      which probably is an indirect effect of different microbial populations. These
      results suggest that the role of adsorption in the anaerobic treatment of complex
      substrates containing fat cannot be overlooked, especially for flocculent sludge
      systems, since organic matter accumulation could cause process failure due to
      biomass washout.

PMID- 12790680
TI  - A novel heterofunctional epoxy-amino sepabeads for a new enzyme immobilization
      protocol: immobilization-stabilization of beta-galactosidase from Aspergillus
      oryzae.
AB  - The properties of a new and commercially available amino-epoxy support (amino
      epoxy-Sepabeads) have been compared to conventional epoxy supports to immobilize
      enzymes, using the beta-galactosidase from Aspergillus oryzae as a model enzyme.
      The new support has a layer of epoxy groups over a layer of ethylenediamine that
      is covalently bound to the support. This support has both a great anionic
      exchanger strength and a high density of epoxy groups. Epoxy supports require the
      physical adsorption of the proteins onto the support before the covalent binding
      of the enzyme to the epoxy groups. Using conventional supports the immobilization
      rate is slow, because the adsorption is of hydrophobic nature, and immobilization
      must be performed using high ionic strength (over 0.5 M sodium phosphate) and a
      support with a fairly hydrophobic nature. Using the new support, immobilization
      may be performed at moderately low ionic strength, it occurs very rapidly, and it
      is not necessary to use a hydrophobic support. Therefore, this support should be
      specially recommended for immobilization of enzymes that cannot be submitted to
      high ionic strength. Also, both supports may be expected to yield different
      orientations of the proteins on the support, and that may result in some
      advantages in specific cases. For example, the model enzyme became almost fully
      inactivated when using the conventional support, while it exhibited an almost
      intact activity after immobilization on the new support. Furthermore, enzyme
      stability was significantly improved by the immobilization on this support (by
      more than a 12-fold factor), suggesting the promotion of some multipoint covalent
      attachment between the enzyme and the support (in fact the enzyme adsorbed on an
      equivalent cationic support without epoxy groups was even slightly less stable
      than the soluble enzyme).

PMID- 12790681
TI  - Rapid evaluation of oxygen and water permeation through microplate sealing tapes.
AB  - Eight commercially available microplate sealing tapes and 10 other suitable
      materials (transparent wound dressings) are compared qualitatively in terms of
      their ability to minimize water evaporation from a multiwell plate while
      maintaining the oxygen supply as high as possible, which is necessary for
      applications like aerobic growth. The transparency and sterility of the products
      are considered as well. All evaluated commercially available sealing tapes fall
      into one of the following two classes: (1) O(2) transfer is comparable to that of
      an unsealed plate, but water vapor retention is relatively low, or (2) O(2)
      transfer via the sealing is slower, but the water retention capability is
      comparably high. All but one of the evaluated wound dressings fall under the
      second class. That dressing, however, constitutes a compromise by showing both
      moderate O(2) permeability and medium water retention. But the estimated mass
      transport in a microtiter plate sealed with this dressing is about 5 times slower
      than that of an unsealed 96 well plate. The aim of this publication is to enable
      the reader to choose a microtiter plate sealing from the materials evaluated
      within this work and to use the rapid methods described herein to easily perform
      tests of additional sealing materials.

PMID- 12790682
TI  - The snowball effect in fed-batch bioreactions.
AB  - The bioreactor will play an important role in future biological manufacturing.
      For economic profit, important profiles of the feed rate in fed-batch cultures
      have been discussed. Unfortunately, the optimal feed rate is less robust. In
      these studies there exists the snowball effect in a substrate-inhibited
      bioprocess, in which substrate is accumulated due to uncertain parameters in the
      model or feed-rate error. The snowball effect also exists in multi-substrate
      limited processes. In further studies, the interaction between the substrates has
      been higher in essential substrates than in growth-enhancing substrates. In a
      typical fed-batch bioreactor, the amount of the product can be reduced to 1% or
      less when the snowball effect arises. A new control structure, i.e., an off-line
      optimized feedforward controller added to a gain-scheduling PI(2)D feedback
      controller, is proposed to eliminate the troublesome snowball effect. The
      proposed control strategy recovers the yield up to 95%. Moreover, the robustness
      of the proposed control structure is demonstrated by simulation.

PMID- 12790683
TI  - Studies on production of ajmalicine in shake flasks by multiple shoot cultures of
      Catharanthus roseus.
AB  - The effects of different concentrations of indole-3-acetic acid (IAA) and
      benzyladenine (BA) on production of ajmalicine by multiple shoot cultures of
      Catharanthus roseus (C. roseus) were studied. By supplementing Murashige and
      Skoog's (MS) medium with a high concentration of IAA (11.42 microM) and a low
      concentration of BA (2.22 microM), shoot cultures accumulated high levels of
      ajmalicine. When culture medium was fortified with a low concentration of IAA
      (2.85 microM) and a high concentration of BA (8.90 microM), shoots released high
      levels of ajmalicine into the culture medium. Quantification of ajmalicine was
      performed by high performance liquid chromatography (HPLC). The highest
      concentration of ajmalicine production (0.166% dry wt) was obtained by shoot
      cultures grown in MS medium containing IAA (11.42 microM) on 20 days of
      cultivation. Shoot cultures accumulated ajmalicine 4.2-fold more in IAA (11.42
      microM) supplemented medium compared with the high concentration of BA (8.90
      microM). The content of ajmalicine concentration in the medium was quantified.
      Shoot cultures grown in BA (8.90 microM) supplemented medium released the maximum
      production of ajmalicine (0.853 g/L) into the culture medium after 15 days of
      cultivation. The experimental data show that the secretion of ajmalicine was 2
      fold more into the culture medium supplemented with a high concentration of BA
      compared to that with a low concentration of BA. Data presented here show that
      production of ajmalicine by shoot cultures is not correlated with growth rate.
      Dimeric indole alkaloids vincristine and vinblastine were not present in shoot
      cultures. Ajmalicine production by shoot cultures was 2.4-fold higher compared to
      leaves of 1-year-old naturally grown plants.

PMID- 12790684
TI  - Applicability of new expression vectors for both engineering uses and biological
      studies.
AB  - To be applicable for both engineering and biological uses, the plasmid with the
      features of tight regulation, high-level expression, and subtle modulation (or
      homogeneous induction) is required. IPTG-inducible promoters are of particular
      interest since they acquire the latter two merits but usually lack stringency. To
      this end, two plasmids have been developed to contain the T7 A1 promoter along
      with either lacI(q) or lacI gene. As a production system, the cells harboring the
      plasmids with the lacZ gene clone enabled production of the maximal protein
      accounting for 35% total cell content upon induction by a saturating IPTG level.
      This protein yield is amplified over 700-fold relative to that at the uninduced
      state. As a system for biological study, the ppc negative strain bearing the
      plasmid with the ppc gene clone failed to grow on glucose without IPTG induction
      but immediately resumed its growth in the presence of IPTG. Moreover, the level
      of the ppc gene product in the cell was varied by various IPTG, and the result
      revealed that the wild-type ppc level was sufficient to support the saturated
      growth of the cell on glucose. Overall, it illustrates the applicability of these
      plasmids to needs in the post-genome era.

PMID- 12790685
TI  - Bioconversion of linoleic acid into conjugated linoleic acid by immobilized
      Lactobacillus reuteri.
AB  - Lactobacillus reuteri was immobilized on silica gel to evaluate the bioconversion
      of linoleic acid (LA) into conjugated linoleic acid (CLA), consisting of cis
      9,trans-11 and trans-10,cis-12 isomers. The amount of cell to carrier, the
      reaction time, and the substrate concentration, pH, and temperature for CLA
      production were optimized at 10 mg of cells/(g of carrier), 1 h, 500 mg/L LA,
      10.5, and 55 degrees C, respectively. In the presence of 1.0 mM Cu(2+), CLA
      production increased by 110%. Under the optimal conditions, the immobilized cells
      produced 175 mg/L CLA from 500 mg/L LA for 1 h with a productivity of 175
      mg/(L.h) and accumulated 5.5 times more CLA than that obtained from bioconversion
      by free washed cells. The CLA-producing ability of reused cells was investigated
      over five reuse reactions and was maximal at pH 7.5, 25 degrees C, and 1.0 mM
      Cu(2+). The total amount of CLA by the combined five reuse reactions was 344 mg
      of CLA/L reaction volume. This was 8.6 times higher than the amount obtained from
      reuse reactions by free washed cells.

PMID- 12790686
TI  - Study of protein splicing and intein-mediated peptide bond cleavage under high
      cell-density conditions.
AB  - Protein splicing elements (inteins), capable of catalyzing controllable peptide
      bond cleavage reactions, have been used to separate recombinant proteins from
      affinity tags during affinity purification. Since the inteins eliminate the use
      of a protease in the recovery process, the intein-mediated purification system
      has the potential to significantly reduce recovery costs for the industrial
      production of recombinant proteins. Thus far, the intein system has only been
      examined and utilized for expression and purification of recombinant proteins at
      the laboratory scale for cells cultivated at low cell densities. In this study,
      protein splicing and in vitro cleavage of intein fusion proteins expressed in
      high-cell-density fed-batch fermentations of recombinant Escherichia coli were
      examined. Three model intein fusion constructs were used to examine the stability
      and splicing/cleavage activities of the fusion proteins produced under high-cell
      density conditions. The data indicated that the intein fusion protein containing
      the wild-type intein catalyzed efficient in vivo protein splicing during high
      cell-density cultivation. Also, the intein fusion proteins containing modified
      inteins catalyzed efficient thiol-induced in vitro cleavage reactions. The
      results of this study demonstrated the potential feasibility of using the intein
      mediated protein purification system for industrial-scale production of
      recombinant proteins.

PMID- 12790688
TI  - Direct binding and characterization of lipase onto magnetic nanoparticles.
AB  - Lipase was covalently bound onto Fe(3)O(4) magnetic nanoparticles (12.7 nm) via
      carbodiimide activation. The Fe(3)O(4) magnetic nanoparticles were prepared by
      coprecipitating Fe(2+) and Fe(3+) ions in an ammonia solution and treating under
      hydrothermal conditions. The analyses of transmission electron microscopy (TEM)
      and X-ray diffraction (XRD) showed that the size and structure of magnetic
      nanoparticles had no significant changes after enzyme binding. Magnetic
      measurement revealed the resultant lipase-bound magnetic nanoparticles were
      superparamagnetic with a saturation magnetization of 61 emu/g (only slightly
      lower than that of the naked ones (64 emu/g)), a remanent magnetization of 1.0
      emu/g, and a coercivity of 7.5 Oe. The analysis of Fourier transform infrared
      (FTIR) spectroscopy confirmed the binding of lipase onto magnetic nanoparticles.
      The binding efficiency of lipase was 100% when the weight ratio of lipase bound
      to Fe(3)O(4) nanoparticles was below 0.033. Compared to the free enzyme, the
      bound lipase exhibited a 1.41-fold enhanced activity, a 31-fold improved
      stability, and better tolerance to the variation of solution pH. For the
      hydrolysis of pNPP by bound lipase at pH 8, the activation energy within 20-35
      degrees C was 6.4 kJ/mol, and the maximum specific activity and Michaelis
      constant at 25 degrees C were 1.07 micromol/min mg and 0.4 mM, respectively. It
      revealed that the available active sites of lipase and their affinity to
      substrate increased after being bound onto magnetic nanoparticles.

PMID- 12790687
TI  - Pulsed feeding during fed-batch Aspergillus oryzae fermentation leads to improved
      oxygen mass transfer.
AB  - Productivity in many fungal fermentations is detrimentally affected by high broth
      viscosity and consequent reduced oxygen mass transfer capacity. The goal here was
      to determine whether pulsed feeding of limiting carbon in a fungal fermentation
      could lead to reduced viscosity and improved oxygen mass transfer. As a model, an
      industrially relevant recombinant strain of Aspergillus oryzae was grown in
      carbon-limited, fed-batch mode. Maltodextrin was used as a carbon source and was
      added either continuously or in 1.5-min pulses, 3.5 min apart. In both feeding
      modes the same total amount of carbon was added, and carbon feed rate was at
      sufficiently low levels to ensure cultures were always carbon-limited. Compared
      to continuous feeding, pulsed addition of substrate led to smaller fungal
      elements, which resulted in a significant reduction in broth viscosity. This in
      turn led to higher dissolved oxygen concentrations and increased oxygen uptake
      rates during pulsed feeding.

PMID- 12790689
TI  - Fusion to a carrier protein and a synthetic propeptide enhances E7 HPV-16
      production and secretion in Lactococcus lactis.
AB  - An inducible system to improve and stabilize the production of an extremely
      labile protein (E7 antigen of human papillomavirus type 16) was developed in the
      food-grade bacterium Lactococcus lactis. A protein carrier, the staphylococcal
      nuclease Nuc, was fused either to N- or C-termini of E7 protein, and the
      resulting hybrid proteins were rescued from intracellular proteolysis but poorly
      secreted by L. lactis. A synthetic propeptide (LEISSTCDA) was then fused and
      significantly improved the secretion efficiency of the hybrid protein Nuc-E7 by
      L. lactis.

PMID- 12790690
TI  - Role of the non-mevalonate pathway in indole alkaloid production by Catharanthus
      roseus hairy roots.
AB  - The 1-deoxy-D-xylulose-5-phosphate (DXP) pathway (non-mevalonate pathway) leading
      to terpenoids via isopentenyl diphosphate (IPP) has been shown to occur in most
      bacteria and in all higher plants. Treatment with the antibiotic fosmidomycin, a
      specific inhibitor of DXP reductoisomerase, considerably inhibited the
      accumulation of the alkaloids ajmalicine, tabersonine, and lochnericine by
      Catharanthus roseus hairy root cultures in the exponential growth phase. However,
      fosmidomycin did not significantly affect alkaloid levels in stationary phase
      hairy root cultures. Feeding with 1-deoxy-D-xylulose, 10-hydroxygeraniol, or
      loganin resulted in significant increases in alkaloid production by exponential
      phase hairy root cultures. These results suggest that the DXP pathway is a major
      provider of carbon for the monoterpenoid pathway leading to the formation of
      indole alkaloids in C. roseus hairy roots in the exponential phase.

PMID- 12790691
TI  - Current management strategies for coexisting diabetes mellitus and obesity.
AB  - Besides genetic predisposition, obesity is the most important risk factor for the
      development of diabetes mellitus. Weight reduction has been shown to markedly
      improve blood glucose control and vascular risk factors associated with insulin
      resistance in obese individuals with type 2 diabetes. Therapeutic strategies for
      the obese diabetic patient include: (i) promoting weight loss, through lifestyle
      modifications (low-calorie diet and exercise) and antiobesity drugs (orlistat,
      sibutramine, etc.); (ii) improving blood glucose control, through agents
      decreasing insulin resistance (metformin or thiazolidinediones, e.g. pioglitazone
      and rosiglitazone) or insulin needs (alpha-glucosidase inhibitors, e.g. acarbose)
      in preference to agents stimulating defective insulin secretion (sulphonylureas,
      meglitinide analogues); and (iii) treating common associated risk factors, such
      as arterial hypertension and dyslipidaemias, to improve cardiovascular prognosis.
      Whenever insulin is required by the obese diabetic patient after failure to
      respond to oral drugs, it should be preferably prescribed in combination with an
      oral agent, more particularly metformin or acarbose, or possibly a
      thiazolidinedione. When morbid obesity is present, both restoring a good
      glycaemic control and correcting associated risk factors can only be obtained
      through a marked and sustained weight loss. This objective justifies more
      aggressive weight reduction programmes, including very-low-calorie diets and
      bariatric surgery, but only within a multidisciplinary approach and long-term
      strategy.

PMID- 12790692
TI  - Polycystic ovary syndrome and epilepsy: a review of the evidence.
AB  - Overrepresentation of polycystic ovary syndrome (PCOS) in women with epilepsy has
      been described since the early 1980s. While some authors attribute this
      association to an effect of the seizure disorder on the hypothalamic control of
      reproductive function, others have reported a relationship with the use of the
      antiepileptic drug valproic acid (VPA). In this article we review the literature
      on this complex issue, with a detailed analysis of the different reports which
      describe the reproductive endocrine assessment in women with epilepsy. In spite
      of the large number of patients assessed, a clear picture does not emerge, mostly
      because of the wide variability of methodology employed in the different study
      projects and of the small size of many patient samples especially when divided in
      subgroups. However, on the whole these studies suggest that women with epilepsy
      are at risk for developing reproductive endocrine disorders, even if there is not
      yet definite evidence that PCOS may be over-represented in these patients nor
      that VPA may be the cause of endocrine problems. It is likely that both the
      epileptic disorder and the antiepileptic treatment play different roles in the
      development of such disturbances. This hypothesis deserves further prospective
      study in large samples of patients; consistency in methodology, diagnostic
      criteria and presentation of results should always be encouraged in the
      researchers dealing with these projects. In the meantime, women with epilepsy
      should be carefully monitored with regard to menstrual function, bodyweight and
      hyperandrogenism, and evaluation of these parameters should become part of the
      routine evaluation in baseline and follow-up consultations.

PMID- 12790693
TI  - Alemtuzumab.
AB  - Alemtuzumab is an unconjugated, humanised, monoclonal antibody directed against
      the cell surface antigen CD52 on lymphocytes and monocytes. In noncomparative
      phase I/II studies in patients with B-cell chronic lymphocytic leukaemia (B-CLL)
      relapsed after or refractory to alkylating agents and fludarabine, intravenous
      (IV) administration of alemtuzumab 30 mg/day three times weekly for up to 12
      weeks was associated with overall objective response (OR) rates of 21-59%.
      Combining alemtuzumab with fludarabine resulted in ORs >80%. In noncomparative
      studies in patients with previously untreated B-CLL, subcutaneous (SC)
      administration of alemtuzumab alone, or IV in combination with fludarabine, was
      highly effective, achieving OR rates of around 90%. IV alemtuzumab was active in
      patients with chemotherapy-resistant/relapsed T-cell prolymphocytic leukaemia,
      with reported OR rates of 24-76%. Alemtuzumab has been incorporated in novel
      conditioning regimens designed to facilitate stem cell transplantation in
      haematological malignancies. Adverse events with alemtuzumab are predictable and
      manageable. 'First-dose' flulike symptoms, frequently seen after IV infusion, can
      be managed by (pre)medication and minimised by dose escalation (or SC injection).
      Anti-infective prophylaxis is mandatory. Cytopenias are transient, although red
      blood cell and platelet support may be required.

PMID- 12790757
TI  - Molecular pathways of endoplasmic reticulum dysfunctions: possible cause of cell
      death in the nervous system.
AB  - This review summarizes recent information on the role of calcium in the process
      of neuronal injury with special attention to the role of calcium stores in the
      endoplasmic reticulum (ER). Experimental results present evidence that ER is the
      site of complex processes such as calcium storage, synthesis and folding of
      proteins and cell response to stress. ER function is impaired in many acute and
      chronic diseases of the brain which in turn induce calcium store depletion and
      conserved stress responses. Understanding the mechanisms leading to ER
      dysfunction may lead to recognition of neuronal protection strategies.

PMID- 12790758
TI  - The pacemaker activity of interstitial cells of Cajal and gastric electrical
      activity.
AB  - Interstitial cells of Cajal (ICC) are the pacemaker cells in the gut. They have
      special properties that make them unique in their ability to generate and
      propagate slow waves in gastrointestinal muscles. The electrical slow wave
      activity determines the characteristic frequency of phasic contractions of the
      stomach, intestine and colon. Slow waves also determine the direction and
      velocity of propagation of peristaltic activity, in concert with the enteric
      nervous system. Characterization of receptors and ion channels in the ICC
      membrane is under way, and manipulation of slow wave activity markedly alters the
      movement of contents through the gut. Gastric myoelectrical slow wave activity
      produced by pacemaker cells (ICC) can be reflected by electrogastrography (EGG).
      Electrogastrography is a perspective non-invasive method that can detect gastric
      dysrhythmias associated with symptoms of nausea or delayed gastric emptying.

PMID- 12790759
TI  - Genetic isolation of quantitative trait loci for blood pressure development and
      renal mass on chromosome 5 in the spontaneously hypertensive rat.
AB  - Total genome scans of genetically segregating populations derived from
      spontaneously hypertensive rats (SHR) and other rat models of essential
      hypertension suggested a presence of quantitative trait loci (QTL) regulating
      blood pressure on multiple chromosomes, including chromosome 5. The objective of
      the current study was to test directly a hypothesis that chromosome 5 of the SHR
      carries a blood pressure regulatory QTL. A new congenic strain was derived by
      replacing a segment of chromosome 5 in the SHR/Ola between the D5Wox20 and
      D5Rat63 markers with the corresponding chromosome segment from the normotensive
      Brown Norway (BN/Crl) rat. Arterial pressures were directly monitored in
      conscious, unrestrained rats by radiotelemetry. The transfer of a segment of
      chromosome 5 from the BN strain onto the SHR genetic background was associated
      with a significant decrease of systolic blood pressure, that was accompanied by
      amelioration of renal hypertrophy. The heart rates were not significantly
      different in the SHR compared to SHR chromosome 5 congenic strain. The findings
      of the current study demonstrate that gene(s) with major effects on blood
      pressure and renal mass exist in the differential segment of chromosome 5 trapped
      within the new SHR.BN congenic strain.

PMID- 12790697
TI  - Saquinavir: a review of its use in boosted regimens for treating HIV infection.
AB  - Protease inhibitor boosting involves concurrent administration of a protease
      inhibitor, such as saquinavir, plus a potent inhibitor of cytochrome P450 (CYP)
      3A4, usually ritonavir in subtherapeutic doses. Since protease inhibitors are
      extensively metabolised by CYP3A4, this results in a marked increase in systemic
      exposure of saquinavir or other protease inhibitors boosted by ritonavir. As with
      traditional protease inhibitor regimens, boosted regimens are typically used in
      combination with nucleoside reverse transcriptase inhibitors (NRTIs). In protease
      inhibitor-experienced and -naive patients with HIV infection, twice-daily and
      once-daily boosted saquinavir regimens achieved good rates of viral suppression,
      improved CD4+ cell counts and were generally well tolerated in clinical trials.
      Encouraging results have also been reported in a number of small studies in
      heavily pretreated HIV-infected patients who received salvage therapy comprising
      double-boosted regimens of saquinavir plus lopinavir with subtherapeutic doses of
      ritonavir, along with other agents. The largest clinical trials have been
      multicentre, randomised comparisons of twice-daily boosted saquinavir versus
      twice-daily boosted indinavir (MaxCmin1) or lopinavir (MaxCmin2) regimens. In the
      MaxCmin1 study, >90% of patients in both groups had an undetectable viral load
      (<400 copies/mL) after 48 weeks of therapy in the on-treatment analysis. However,
      viral suppression was achieved in significantly more saquinavir than indinavir
      recipients in the intention-to-treat analysis, which appeared to be due to the
      significantly greater percentage of patients in the indinavir group who switched
      from randomised therapy because of adverse events. Interim 24-week results of the
      MaxCmin2 trial indicate that 90% of patients in both groups combined had plasma
      HIV RNA levels <400 copies/mL; final results at 48 weeks will report data
      separately for the boosted regimens of saquinavir and lopinavir. CONCLUSION:
      Boosted protease inhibitor regimens (including two NRTIs) are recommended as a
      first-line option in current HIV treatment guidelines and are used extensively in
      clinical practice. The convenient administration schedule and good
      pharmacokinetic profile associated with boosted saquinavir regimens have the
      potential to increase adherence to therapy and improve antiretroviral effects
      through increased drug exposure. Twice-daily boosted saquinavir is one of the
      most extensively evaluated boosted protease inhibitor regimens and has been shown
      to have good efficacy on surrogate markers of HIV disease as well as significant
      tolerability advantages over boosted indinavir. Once-daily boosted saquinavir
      regimens may be most suitable for HIV-infected patients with busy lifestyles and
      those who would benefit from directly observed therapy.

PMID- 12790760
TI  - Office blood pressure, heart rate and A(-596)G interleukin-6 gene polymorphism in
      apparently healthy Czech middle-aged population.
AB  - The aim of the study was to assess the association between promoter polymorphism
      [A(-596)G] in interleukin-6 gene and office systolic and diastolic blood
      pressures, and the heart rate (HR) in apparently healthy Czech subjects.
      Furthermore, we evaluated the possible influence of gender, BMI and smoking on
      these supposed associations. An age-matched (40-50 years) and gender-matched
      (F/M=81/89) sample of apparently healthy Czech subjects (n=170, F/M=81/89)
      without hypertension, other cardiovascular diseases or diabetes was examined. The
      A(-596)G Il-6 gene polymorphism was detected by the PCR method. No differences in
      genotype distribution and/or allelic frequency was found between groups with
      lower systolic blood pressure (L 122 mm Hg) and higher systolic blood pressure (>
      122 mm Hg). Similarly, no differences in the IL-6 polymorphism were found between
      lower (L 86 mm Hg) and higher (> 86 mm Hg) diastolic blood pressure groups.
      However, we proved a significant increase of genotypes AG+GG as well as the
      allele (-596)G in higher (>78 beats/min) heart rate group. The genotypes AG+GG
      represent significantly higher relative risk for higher HR frequency, especially
      in women. Among lean persons with a low heart rate frequency, fewer AG+GG
      genotypes were determined than among any other subjects. The genotypes AG+GG are
      more frequent in non-smoking persons with higher HR compared to non-smoking
      subjects with lower HR, especially in women. Gender, BMI and smoking
      substantially modify the distribution of A(-596)G Il-6 gene polymorphism in
      apparently healthy persons with lower or higher heart rate.

PMID- 12790761
TI  - A dampening effect of pulse interval variability on blood pressure variations
      with respect to primary variability in blood pressure during exercise.
AB  - The correlation between baroreflex sensitivity (BRS) and the spectrum component
      at a frequency of 0.1 Hz of pulse intervals (PI) and systolic blood pressure
      (SBP) was studied. SBP and PI of 51 subjects were recorded beat-to-beat at rest
      (3 min), during exercise (0.5 W/kg of body weight, 9 min), and at rest (6 min)
      after exercise. BRS was determined by a spectral method (a modified alpha index
      technique). The subjects were divided into groups according to the spectral
      amplitude of SBP at a frequency of 0.1 Hz. The following limits of amplitude (in
      mm Hg) were used: very high > 5.4 (VH); high 5.4 > H > 3 (H); medium 3 > M > 2
      (M), low < 2 (L). We analyzed the relationships between 0.1 Hz variability in PI
      and BRS at rest, during the exercise and during recovery in subgroups VH, H, M,
      L. The 0.1 Hz variability of PI increased significantly with increasing BRS in
      each of the groups with identical 0.1 Hz variability in SBP. This relationship
      was shifted to the lower values of PI variability at the same BRS with a decrease
      in SBP variability. The primary SBP variability increased during exercise. The
      interrelationship between the variability of SBP, PI and BRS was identical at
      rest and during exercise. A causal interrelationship between the 0.1 Hz
      variability of SBP and PI, and BRS was shown. During exercise, the increasing
      primary variability in SBP due to sympathetic activation was present, but it did
      not change the relationship between variability in pulse intervals and BRS.

PMID- 12790696
TI  - Tacrolimus: a further update of its use in the management of organ
      transplantation.
AB  - Extensive clinical use has confirmed that tacrolimus (Prograf) is a key option
      for immunosuppression after transplantation. In large, prospective, randomised,
      multicentre trials in adults and children receiving solid organ transplants,
      tacrolimus was at least as effective or provided better efficacy than cyclosporin
      microemulsion in terms of patient and graft survival, treatment failure rates and
      the incidence of biopsy-proven acute and corticosteroid-resistant rejection
      episodes. Notably, the lower incidence of rejection episodes after renal
      transplantation in tacrolimus recipients was reflected in improved cost
      effectiveness. In bone marrow transplant (BMT) recipients, the incidence of
      tacrolimus grade II-IV graft-versus-host disease was significantly lower with
      tacrolimus than cyclosporin treatment. Efficacy was maintained in renal and liver
      transplant recipients after total withdrawal of corticosteroid therapy from
      tacrolimus-based immunosuppression, with the incidence of acute rejection
      episodes at up to 2 years' follow-up being similar with or without
      corticosteroids. Tacrolimus provided effective rescue therapy in transplant
      recipients with persistent acute or chronic allograft rejection or drug-related
      toxicity associated with cyclosporin treatment. Typically, conversion to
      tacrolimus reversed rejection episodes and/or improved the tolerability profile,
      particularly in terms of reduced hyperlipidaemia. In lung transplant recipients
      with obliterative bronchiolitis, conversion to tacrolimus reduced the decline in
      and/or improved lung function in terms of forced expiratory volume in 1 second.
      Tolerability issues may be a factor when choosing a calcineurin inhibitor.
      Cyclosporin tends to be associated with a higher incidence of significant
      hypertension, hyperlipidaemia, hirsutism, gingivitis and gum hyperplasia, whereas
      the incidence of some types of neurotoxicity, disturbances in glucose metabolism,
      diarrhoea, pruritus and alopecia may be higher with tacrolimus treatment. Renal
      function, as assessed by serum creatinine levels and glomerular filtration rates,
      was better in tacrolimus than cyclosporin recipients at up to 5 years' follow-up.
      CONCLUSION: Recent well designed trials have consolidated the place of tacrolimus
      as an important choice for primary immunosuppression in solid organ
      transplantation and in BMT. Notably, in adults and children receiving
      transplants, tacrolimus-based primary immunosuppression was at least as effective
      or provided better efficacy than cyclosporin microemulsion treatment in terms of
      patient and graft survival, treatment failure and the incidence of acute and
      corticosteroid-resistant rejection episodes. The reduced incidence of rejection
      episodes in renal transplant recipients receiving tacrolimus translated into a
      better cost effectiveness relative to cyclosporin microemulsion treatment. The
      optimal immunosuppression regimen is ultimately dependent on balancing such
      factors as the efficacy of the individual drugs, their tolerability, potential
      for drug interactions and pharmacoeconomic issues.

PMID- 12790762
TI  - Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine,
      lithium and citalopram.
AB  - Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake
      inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium
      carbonicum (Li) have different cardiovascular side-effects. We compared them in
      the prophylactic therapy of periodic affective disorder in remission with TCA,
      SSRI and Li. Our previous papers confirmed the most prominent effects of heart
      electric field parameters in TCA patients (Slavicek et al., 1998). In the present
      work we studied for the first time the dose-dependent changes of ECG, body
      surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40
      SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDL10; age 40+/-5 years;
      treated for depressive disorders or bipolar disorders). The daily doses of
      dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08
      meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were
      measured and calculated by the Cardiag 112.1 diagnostic system. The results have
      shown a relation between the dose of dosulepine and extremum (maximum and
      minimum) of depolarization isoarea map in dosulepine, but not in citalopram
      patients. The repolarization BSPM changes were most pronounced in SSRI patients.
      Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM
      changes. The present results correspond with our previous observations.

PMID- 12790763
TI  - Plasma levels of dosulepine and heart electric field.
AB  - Antidepressants, particularly tricyclic (TCA) antidepressants, may have
      cardiotoxic effects, such as cardiac arrhythmias, especially in patients with
      cardiovascular diseases. For most of TCA, no exact correlation between dosage,
      plasma levels and changes of ECG parameters of standard ECG has been found. So
      far, no relationship between dosulepine plasma levels and heart electric field
      parameters has been studied. We selected 18 female outpatient subjects diagnosed
      with recurrent depressive disorders, currently in the remission phase (HAMD <
      10), without any cardiovascular disease. Patients were treated with daily
      dosulepine doses of 25-125 mg for 4-8 weeks. 30 heart electric field parameters
      were analyzed by Cardiag 128.1 diagnostic system as part of BSPM (Body Surface
      Potential Mapping). Acquired data were correlated with dosulepine plasma levels
      by means of Spearman's rank order correlation test. Four ECG parameters showed a
      significant correlation with dosulepine plasma levels: QRS axis deviation in
      frontal plane (p=0.01), DIAM 40 max (p<0.05), QRS-STT angle in transversal and
      left sagittal plane (p<0.05). The demonstrated changes confirmed dosulepine
      influence on the early myocardium depolarization phase and the correlation of
      this effect with dosulepine dose (its plasma concentration). The higher the
      dosulepine level, the more marked are the changes of the QRS-STT angle in
      transversal and sagittal planes and the changes in the QRS axis deviation in
      frontal plane. Repeatedly recorded changes in the heart electric field were
      dosulepine-specific and dependent on its plasma levels.

PMID- 12790764
TI  - Hydrogen peroxide production by alveolar macrophages is increased and its
      concentration is elevated in the breath of rats exposed to hypoxia: relationship
      to lung lipid peroxidation.
AB  - Hypoxic exposure triggers a generation of reactive oxygen species that initiate
      free radical damage to the lung. Hydrogen peroxide is the product of alveolar
      macrophages detectable in the expired breath. We evaluated the significance of
      breath H(2)O(2) concentration for the assessment of lung damage after hypoxic
      exposure and during posthypoxic period. Adult male rats were exposed to
      normobaric hypoxia (10 % O(2)) for 3 hours or 5 days. Immediately after the
      hypoxic exposure and then after 7 days or 14 days of air breathing, H(2)O(2) was
      determined in the breath condensate and in isolated lung macrophages. Lipid
      peroxidation was measured in lung homogenates. Three-hour hypoxia did not cause
      immediate increase in the breath H(2)O(2); 5-day hypoxia increased breath
      H(2)O(2) level to 458 %. After 7 days of subsequent air breathing H2O2 was
      elevated in both groups exposed to hypoxia. Increased production of H(2)O(2) by
      macrophages was observed after 5 days of hypoxia and during the 7 days of
      subsequent air breathing. Lipid peroxidation increased in the periods of enhanced
      H(2)O(2) generation by macrophages. As the major increase (1040 %) in the breath
      H(2)O(2) concentration found 7 days after 3 hours of hypoxia was not accompanied
      by lipid peroxidation, it can be concluded that the breath H(2)O(2) is not a
      reliable indicator of lung oxidative damage.

PMID- 12790765
TI  - Effect of head-down bed rest on the neuroendocrine response to orthostatic stress
      in physically fit men.
AB  - The role of neuroendocrine responsiveness in the development of orthostatic
      intolerance after bed rest was studied in physically fit subjects. Head-down bed
      rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic
      training. The standing test was performed before, after training and on day 4 of
      the HDBR. Orthostatic intolerance was observed in one subject before and after
      training. The blood pressure response after training was enhanced (mean BP
      increments 18+/-2 vs. 13+/- 2 mm Hg, p<0.05, means +/- S.E.M.), although
      noradrenaline response was diminished (1.38+/-0.18 vs. 2.76+/-0.25 mol.l(-1),
      p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP
      response was blunted, and noradrenaline as well as plasma renin activity (PRA)
      responses were augmented (NA 3.10+/-0.33 mol.l(-1), p<0.001; PRA 2.98+/-1.12 vs.
      0.85+/-0.15 ng.ml(-1), p<0.05). Plasma noradrenaline, adrenaline and aldosterone
      responses in orthostatic intolerant subjects were similar to the tolerant group.
      We conclude that six weeks of training attenuated the sympathetic response to
      standing and had no effect on the orthostatic tolerance. In orthostatic
      intolerance the BP response induced by subsequent HDBR was absent despite an
      enhanced sympathetic response.

PMID- 12790766
TI  - Inhibin B, follicle stimulating hormone, luteinizing hormone, and estradiol and
      their relationship to the regulation of follicle development in girls during
      childhood and puberty.
AB  - Inhibin B, produced by granulosa cells in the ovary, is a heterodimeric
      glycoprotein suppressing synthesis and secretion of the follicle stimulating
      hormone (FSH). The aim of the present study was to determine hormone profiles of
      inhibin B, FSH, luteinizing hormone (LH), and estradiol in girls during childhood
      and puberty and to evaluate whether inhibin B is a marker of follicle
      development. We examined the correlation between inhibin B and gonadotropins and
      estradiol during the first two years and across the pubertal development. Using a
      specific two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels
      were measured in the serum of 53 healthy girls divided into 8 groups according to
      age. In addition, serum FSH, LH, and estradiol were measured by chemiluminescent
      immunoassay in all serum samples. A rise in serum levels of inhibin B (55.2+/-7.3
      ng/l, mean +/- S.E.M.) and FSH (1.78+/-0.26 UI/l), concomitant with a moderate
      increment of serum LH (0.36+/-0.09 UI/l) and estradiol (45.8+/-12.2 pmol/l)
      concentrations was observed during the first three months of life and declined to
      prepubertal concentrations thereafter. A strong positive correlation between
      inhibin B and FSH (r = 0.48, p<0.05), LH (r = 0.68, p<0.001) and estradiol (r =
      0.59, p<0.01) was demonstrated during the first 2 years of life. A rise in serum
      levels of inhibin B, FSH, LH, and estradiol was found throughout puberty. Inhibin
      B had a strong positive correlation with FSH (stage I of puberty: r = 0.64,
      p<0.05; stage II of puberty: r = 0.86, p<0.01), LH (I: r = 0.61, p<0.05; II: r =
      0.67, p<0.05), and estradiol (II: r = 0.62, p<0.05) in early puberty. From
      pubertal stage II, inhibin B lost this relationship to gonadotropins and
      estradiol. Serum inhibin B and FSH levels increased significantly during pubertal
      development, with the highest peak found in stage III of puberty (133.5+/-14.3
      ng/l), and decreased thereafter. In conclusion, inhibin B is produced in a
      specific pattern in response to gonadotropin stimulation and plays an important
      role in the regulation of the hypothalamic-pituitary-gonadal axis during
      childhood and puberty in girls. Inhibin B is involved in regulatory functions in
      developing follicles and seems to be a sensitive marker of ovarian follicle
      development.

PMID- 12790767
TI  - Soluble leptin receptor levels in patients with chronic renal failure.
AB  - Soluble leptin receptor (SLR) is the extracellular part of the leptin receptor.
      This protein is released into circulation and constitutes the main circulating
      leptin-binding protein. The aim of our study was to measure SLR concentrations in
      patients with chronic renal failure (CRF) and healthy subjects and to explore the
      relationship of SLR to other hormones and cytokines. The patients with CRF had
      significantly higher serum leptin, TNF-alpha and insulin levels than healthy
      subjects (25.1+/-23.5 vs. 9.4+/-7.6 ng.ml(-1) (S.D.); 14.2+/-4.2 vs. 4.55+/-2.5
      ng.ml(-1); 39.8+/-36.1 vs. 20.3+/-11.1 mU.l(-1)). Serum soluble leptin receptor
      levels did not differ between these groups (19.1+/-11.3 vs. 19.6+/-6.1 U.ml(-1)).
      An inverse relationship between serum SLR and leptin levels was found in both
      groups. In patients with CRF the inverse relationship between SLR and insulin,
      body fat content and total protein levels were also found, while in healthy
      subjects only inverse relationship of SLR with insulin and albumin concentrations
      were detected. We conclude that soluble leptin receptor levels in patients with
      chronic renal failure do not differ from those of healthy subjects despite higher
      serum leptin levels in CRF patients. The physiological consequences of this
      finding require further investigation.

PMID- 12790768
TI  - TGF-beta1 expression and chronic allograft nephropathy in protocol kidney graft
      biopsy.
AB  - Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause
      of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine
      associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy,
      protocol biopsy has been suggested to be a beneficial method for early CAN
      detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine
      based immunosuppression-treated kidney transplant recipients with stable renal
      function 12 months after renal transplantation. Biopsy specimens were analyzed
      morphologically according to Banff-97' criteria and immunohistologically for TGF
      beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels
      and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I
      was found to be the most frequent one (44 %). A normal finding within the graft
      was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA
      was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline
      changes were present. We found a significant correlation between CAN grade and
      creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well
      as body mass index (p<0.01). There was a significant correlation between chronic
      vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF
      beta1 staining and chronic vasculopathy (p<0.01). There were no relations between
      morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma
      lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the
      donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft
      biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked
      with chronic vasculopathy.

PMID- 12790769
TI  - Serum alpha-glutathione S-transferase as a sensitive marker of hepatocellular
      damage in patients with cystic fibrosis.
AB  - The aim of the study was to evaluate serum a-glutathione S-transferase (s-GSTA)
      levels in patients with cystic fibrosis (CF) and to compare s-GSTA with other
      liver function tests and with a hepatic ultrasound scan (US). The cytosolic
      enzyme, alpha-glutathione S-transferase is predominantly found in the liver and
      is distributed uniformly in the liver tissue. In our study s-GSTA levels were
      measured in 37 CF patients aged 1 to 28 years (mean age 10.4 years, 24 males).
      The control group consisted of 27 patients aged 2 to 17 years (mean age 8.5
      years, 18 males). The presence of hepatobiliary abnormalities was assessed by
      clinical examination, ultrasound scan, s-GSTA, and conventional liver enzymes:
      alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate
      aminotransferase (AST) and gama-glutamyl transferase (GMT). The calculated 5-95 %
      range of s-GSTA for the control group was 0.098-2.54 microg/l, for the CF group
      0.43-9.76 microg/l. Mean s-GSTA level in the control group was 1.55 microg/l
      (S.D.=1.57), and 2.05 micro/l (S.D.=2.60) in the CF group. In the group of CF
      patients, the serum levels were significantly higher than in the control group
      (P<0.01). No significant correlation existed in the CF group between s-GSTA and
      conventional liver tests (ALT, AST, ALP and GMT). Four patients in the CF group
      had hepatobiliary abnormalities detectable by conventional liver tests, s-GSTA
      and US. Four patients had abnormal s-GSTA, while conventional liver tests and US
      were normal. One other patient had abnormal hepatic US, but normal standard liver
      tests and s-GSTA. The study has suggested that a raised s-GSTA level might be a
      marker of possible pathological changes of the hepatobiliar system in CF
      patients. Serum GSTA seems to be a more sensitive marker than transaminases for
      the monitoring of hepatocellular integrity and as an early predictor of hepatic
      damage.

PMID- 12790770
TI  - Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase
      IV-like activity baring enzymes in human blood plasma and glioma cell lines.
AB  - Quaternary benzo[c]phenanthridine alkaloids (QBA), fagaronine (FA), sanguinarine
      (SA), chelerythrine (CHE) and the QBA extract from Macleya cordata (EX) exerted
      differential inhibitory effect on the hydrolytic activity of particular
      dipeptidyl peptidase (DPP)-like enzyme isolated from human blood plasma and from
      human and rat glioma cell lines. The low-MW form of DPP-IV-like enzyme activity,
      corresponding most probably to DPP-8, observed only in glioma cells but not in
      human plasma, was inhibited preferentially by SA, CHE and EX, and only slightly
      by FA. The alkaloid inhibitory effect was concentration-dependent in the range 25
      150 mM and directly pH-related. In addition, a subtle but consistent inhibition
      of the intermediate-MW form of DPP-IV-like enzyme activity, ascribed to DPP
      IV/CD26, observed only in human plasma and of the attractin (high-MW form of DPP
      IV-like enzyme activity, expressed in U87 glioma cells) by the studied alkaloids
      was observed. We conclude that some of the QBA biological effects could be
      determined by tissue and cell type specific dipeptidyl peptidase IV-like
      molecules expression pattern.

PMID- 12790771
TI  - Hippocampal vasopressin release evoked by N-methyl D-aspartate (NMDA)
      microdialysis.
AB  - Hippocampus is a brain structure containing vasopressin (AVP) fibers and specific
      binding sites for this peptide. There is growing evidence that AVP and its
      metabolites participate in glutamate-mediated plasticity of the hippocampus. The
      aim of the present study was to evaluate the influence of NMDA on AVP release in
      the rabbit hippocampus. Caudate nucleus was chosen as the reference structure.
      The mentioned brain structures were simultaneously microdialyzed with 0.9 % NaCl
      solution. AVP was determined in the outflowing fluid by radioimmunoassay. The
      mean basal AVP content in the fluid outflowing from the hippocampus was
      significantly greater than that from the caudate nucleus. The addition of K(+)
      into the fluid perfusing the probes implanted into the hippocampus and caudate
      nucleus significantly increased AVP release into the extracellular fluid of both
      brain structures. NMDA applied into the mentioned brain structures increased AVP
      release only from the hippocampus but not from the caudate nucleus. Our findings
      indicate a role which NMDA receptors play in AVP release into the extracellular
      fluid of the hippocampus.

PMID- 12790772
TI  - Components of cigarette smoke inhibit expansion of oocyte-cumulus complexes from
      porcine follicles.
AB  - The role of alkaloids in cigarette smoke was investigated in the cumulus
      expansion of oocyte-cumulus complexes (OCC) isolated from large antral porcine
      follicles. Suppression of the cumulus expansion stimulated by FSH was observed in
      the presence of different concentration of cadmium, anabasine and nicotine but
      not its metabolite cotinine. There were comparable inhibitory effects of cadmium
      and nicotine on the synthesis and accumulation of hyaluronic acid in the
      cell/matrix compartment of OCC. The inhibitory effect of tested compounds on the
      cumulus expansion was accompanied by decreased progesterone synthesis by cumulus
      cells during 42 h incubation of OCC with FSH. The results suggest that cigarette
      smoking may affect intrafollicular processes, which are responsible for normal
      ovulation and fertilization.

PMID- 12790773
TI  - Proceedings of the International Congress on Hormonal Steroids and Hormones and
      Cancer. 21-25 October 2002, Fukuoka, Japan.
AB  - International Congress provide the impetus to facilitate the presentation and
      discussion of a wide spectrum of opinions, which then lead to the development of
      a broad perspective of understanding. The format chosen is usually designed to
      accomplish three general aims: the critical review of rapidly advancing and
      important fields, the integration of cutting edge information considered to
      represent new pathways of understanding, and the presentation of exciting and
      provocative preliminary data. The meeting in Fukuoka, Japan held on October 21-25
      2002 served these purposes well. In addition, this meeting created unique synergy
      imparted by the joining of two previously independent congresses, the
      International Congress on Hormonal Steroids (ICHS) and the International Congress
      on Hormones and Cancer (ICHC). This joint congress continued a long tradition
      since it represented the 11th ICHS and 7th ICHC meetings. The marriage of these
      two congresses was timely and reflected the increasing understanding that
      hormones, growth factors, cytokines, and chemokines all work through receptors
      and influence cancer cell proliferation and apoptosis, as well as differentiated
      function. By providing a forum to summarize recent data from several disparate
      areas, this combined congress weaved a fabric of interlocking information based
      upon evolving principles of cellular biology and clinical intervention.

PMID- 12790774
TI  - Adaptive hypersensitivity to estrogen: mechanism for superiority of aromatase
      inhibitors over selective estrogen receptor modulators for breast cancer
      treatment and prevention.
AB  - Clinical observations suggest that human breast tumors can adapt to endocrine
      therapy by developing hypersensitivity to estradiol (E(2)). To understand the
      mechanisms responsible, we examined estrogenic stimulation of cell proliferation
      in a model system and provided in vitro and in vivo evidence that long-term E(2)
      deprivation (LTED) causes "adaptive hypersensitivity". The enhanced responses to
      E(2) do not involve mechanisms acting at the level of transcription of estrogen
      regulated genes. We found no evidence of hypersensitivity when examining the
      effects of E(2) on regulation of c-myc, pS2, progesterone receptor, several
      estrogen receptor (ER) reporter genes, or c-myb in hypersensitive cells. Estrogen
      deprivation of breast cells long-term does up-regulate both the MAP kinase and
      phosphatidyl-inositol 3-kinase pathways. As a potential explanation for up
      regulation of these signaling pathways, we found that ERalpha is 4- to 10-fold up
      regulated and co-opts a classic growth factor pathway using Shc, Grb-2 and Sos.
      This induces rapid non-genomic effects which are enhanced in LTED cells. E(2)
      binds to cell membrane-associated ERalpha, physically associates with the adapter
      protein SHC, and induces its phosphorylation. In turn, Shc binds Grb-2 and Sos,
      which results in the rapid activation of MAP kinase. These non-genomic effects of
      E(2) produce biological effects as evidenced by Elk activation and by
      morphological changes in cell membranes. Further proof of the non-genomic effects
      of E(2) involved use of cells which selectively expressed ERalpha in the nucleus,
      cytosol and cell membrane. We created these COS-1 "designer cells" by
      transfecting ERalpha lacking a nuclear localization signal and containing a
      membrane localizing signal. The concept of "adaptive hypersensitivity" and the
      mechanisms responsible for this phenomenon have important clinical implications.
      Adaptive hypersensitivity would explain the superiority of aromatase inhibitors
      over the selective ER modulators (SERMs) for treatment of breast cancer. The
      development of highly potent third-generation aromatase inhibitors allows
      reduction of breast tissue E2 to very low levels and circumvents the enhanced
      sensitivity of these cells to the proliferative effects of E(2). Clinical trials
      in the adjuvant, neoadjuvant and advanced disease settings demonstrate the
      greater clinical efficacy of the aromatase inhibitors over the SERMs. More recent
      observations indicate that the aromatase inhibitors are superior for the
      prevention of breast cancer as well. These observations may be explained by the
      hypothesis that estrogens induce breast cancer both by stimulating cell
      proliferation and by their metabolism to genotoxic products. The SERMs block ER
      mediated proliferation only, whereas the aromatase inhibitors exert dual effects
      on proliferation and genotoxic metabolite formation.

PMID- 12790775
TI  - The role of vitamin D and retinoids in controlling prostate cancer progression.
AB  - Prostate cancer is a leading cause of cancer-related deaths in many countries.
      Premalignant lesions and invasive cancer occur more frequently in the prostate
      than in any organ other than the skin. Yet, the incidence of clinically detected
      prostate cancer is much lower than the histopathological incidence. The slow
      growth of prostate cancer and the low incidence of clinically manifest disease in
      some geographical locations or racial/ethnic groups suggest that prostate cancer
      can be controlled, perhaps by dietary factors. Vitamin D and retinoids have
      emerged as leading candidates both to prevent and to treat prostate cancer. Many
      of the activities of these compounds, established from epidemiological studies,
      research with cell culture and animal models, and clinical trials, are consistent
      with tumor suppressor effects. However, retinoids may have additional tumor
      enhancer properties that balance or negate anti-cancer activity. This perhaps
      explains the overall lack of protective effects of vitamin A compounds against
      prostate cancer found in epidemiological studies, and the minimal efficacy of
      retinoids in clinical trials to treat prostate cancer. While current efforts
      focus on developing strategies to use vitamin D compounds to control prostate
      cancer, the possibility exists that prostate cancer cells may become resistant to
      tumor suppressor effects of vitamin D. Analyses of experimental model systems
      show that prostate cancer cells become less sensitive to vitamin D through loss
      of receptors or signaling molecules that mediate vitamin D's actions, or through
      changes in metabolic enzymes that synthesize or degrade vitamin D compounds. The
      potential promise of exploiting vitamin D to control prostate cancer is tempered
      by the possibility that prostate cancer, perhaps even at early stages, may
      develop mechanisms to escape tumor suppressor activities of vitamin D and/or
      retinoids.

PMID- 12790776
TI  - The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic
      perspectives.
AB  - CYR61 (CNN1), a member of the cysteine rich 61/connective tissue growth
      factor/nephroblastoma overexpressed (CYR61/CTFG/NOV) family of growth regulators
      (CNN), is a pro-angiogenic factor that mediates diverse roles in development,
      cell proliferation, and tumorigenesis. We have recently shown that CYR61 is
      overexpressed in invasive and metastatic human breast cancer cells. Accordingly,
      elevated levels of CYR61 in breast cancer are associated with more advanced
      disease. Unfortunately, the exact mechanisms by which CYR61 promotes an
      aggressive breast cancer phenotype are still largely unknown. This review
      examines the functional role of CYR61 in breast cancer disease, presenting
      evidence that CYR61 signaling may play a major role in estrogen- as well as
      growth factor-dependent breast cancer progression. We also emphasize the
      functional significance of the molecular connection of CYR61 and its integrin
      receptor alpha(v)beta(3) enhancing breast cancer aggressiveness. Moreover, we
      describe experimental evidence that establishes a novel role for CYR61
      determining the protection of human breast cancer cells against chemotherapy
      induced apoptosis through its interactions with the integrin receptor
      alpha(v)beta(3). All these findings delineate a new noteworthy function of a
      CYR61/alpha(v)beta(3) autocrine-paracrine signaling pathway within both
      angiogenesis and breast cancer progression, which would allow a dual anti
      angiogenic and anti-tumor benefit with a single drug.

PMID- 12790777
TI  - Melatonin and mammary cancer: a short review.
AB  - Melatonin is an indolic hormone produced mainly by the pineal gland. The former
      hypothesis of its possible role in mammary cancer development was based on the
      evidence that melatonin down-regulates some of the pituitary and gonadal hormones
      that control mammary gland development and which are also responsible for the
      growth of hormone-dependent mammary tumors. Furthermore, melatonin could act
      directly on tumoral cells, as a naturally occurring antiestrogen, thereby
      influencing their proliferative rate. The first reports revealed a low plasmatic
      melatonin concentration in women with estrogen receptor (ER)-positive breast
      tumors. However, later studies on the possible role of melatonin on human breast
      cancer have been scarce and mostly of an epidemiological type. These studies
      described a low incidence of breast tumors in blind women as well as an inverse
      relationship between breast cancer incidence and the degree of visual impairment.
      Since light inhibits melatonin secretion, the relative increase in the melatonin
      circulating levels in women with a decreased light input could be interpreted as
      proof of the protective role of melatonin on mammary carcinogenesis. From in vivo
      studies on animal models of chemically induced mammary tumorigenesis, the general
      conclusion is that experimental manipulations activating the pineal gland or the
      administration of melatonin lengthens the latency and reduces the incidence and
      growth rate of mammary tumors, while pinealectomy usually has the opposite
      effects. Melatonin also reduces the incidence of spontaneous mammary tumors in
      different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a
      high tumoral incidence. In vitro experiments, carried out with the ER-positive
      MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological
      concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in
      a reversible way, cell proliferation, (b) increases the expression of p53 and
      p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the
      metastasic capacity of these cells and counteracts the stimulatory effect of
      estradiol on cell invasiveness; this effect is mediated, at least in part, by a
      melatonin-induced increase in the expression of the cell surface adhesion
      proteins E-cadherin and beta(1)-integrin. The direct oncostatic effects of
      melatonin depends on its interaction with the tumor cell estrogen-responsive
      pathway. In this sense it has been demonstrated that melatonin down-regulates the
      expression of ERalpha and inhibits the binding of the estradiol-ER complex to the
      estrogen response element (ERE) in the DNA. The characteristics of melatonin's
      oncostatic actions, comprising different aspects of tumor biology as well as the
      physiological doses at which the effect is accomplished, give special value to
      these findings and encourage clinical studies on the possible therapeutic value
      of melatonin on breast cancer.

PMID- 12790778
TI  - Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and
      progression.
AB  - Luteinizing hormone-releasing hormone (LHRH) is the key hormone in the control of
      reproductive functions. In recent years, it has become evident that LHRH might
      act as a growth modulatory factor in tumors of the reproductive system. We have
      shown that in prostate cancer cells LHRH is expressed, together with its
      receptors, to negatively regulate cell proliferation. In these cells, LHRH acts
      as an antimitogenic factor through the activation of the Gi-cAMP intracellular
      signaling pathway. More recently, we investigated whether an LHRH-based autocrine
      system might also be expressed in tumors that are not classically related to the
      reproductive tract, such as melanoma. Malignant melanoma is known to be
      characterized not only by a high proliferation rate, but also by an aggressive
      metastatic behavior. We have demonstrated that both LHRH and LHRH receptors are
      expressed in human melanoma cells (BLM and Me15392). Activation of LHRH receptors
      by means of a potent LHRH agonist (Zoladex) significantly inhibited cell
      proliferation. The LHRH agonist also reduced the ability of melanoma cells to
      invade a reconstituted basement membrane (Matrigel) and to migrate in response to
      a chemotactic stimulus. These data indicate that: (a) in prostate cancer cells
      the LHRH receptor is coupled to a Gi-cAMP signal transduction pathway; (b) LHRH
      and LHRH receptors are also expressed in tumors that are not classically related
      to the reproductive system, such as melanoma; in melanoma cells, LHRH might act
      as an inhibitory factor on both cell proliferation and metastatic behavior. It is
      suggested that, in melanoma, LHRH receptors might represent a diagnostic marker
      and a possible molecular target for new therapeutic approaches for this
      pathology.

PMID- 12790779
TI  - Potential role of gonadotrophin-releasing hormone (GnRH)-I and GnRH-II in the
      ovary and ovarian cancer.
AB  - Gonadotrophin-releasing hormone (GnRH) functions as a key neuroendocrine
      regulator of the hypothalamic-pituitary-gonadal axis. In addition to the
      hypothalamus and pituitary gland, GnRH and its receptor have been detected in
      other reproductive tissues including the gonads, placenta and tumours arising
      from these tissues. Recently, a second form of GnRH (GnRH-II) and type II GnRH
      receptor have been found in normal ovarian surface epithelium and neoplastic
      counterparts. The two types of GnRH may play an important role as an
      autocrine/paracrine regulator of reproductive functions and ovarian tumour
      growth. In this review, the distribution and potential roles of GnRH-I/-II and
      their GnRH receptors in the ovarian cells and ovarian cancer will be discussed.

PMID- 12790780
TI  - Estrogen and antiestrogen regulation of cell cycle progression in breast cancer
      cells.
AB  - The central involvement of estrogen in the development of the mammary gland and
      in the genesis of breast cancer has lent impetus to studies of the links between
      estrogen action and the cell cycle machinery. Recent studies of the estrogenic
      regulation of molecules with known roles in the control of G1/S phase progression
      have resulted in significant advances in understanding these links. Estrogens
      independently regulate the expression and function of c-Myc and cyclin D1 and the
      induction of either c-Myc or cyclin D1 is sufficient to recapitulate the effects
      of estrogen on cell cycle progression. These pathways converge at the activation
      of cyclin E-Cdk2 complexes. The active cyclin E-Cdk2 complexes are depleted of
      the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) because of estrogen
      mediated inhibition of nascent p21(WAF1/CIP1). Insulin and estrogen
      synergistically stimulate cell cycle progression, and the ability of estrogen to
      antagonize an insulin-induced increase in p21(WAF1/CIP1) gene expression appears
      to underlie this effect. Antiestrogen treatment of MCF-7 cells leads to an acute
      decrease of c-Myc expression, a subsequent decline in cyclin D1, and ultimately
      arrest of cells in a state with features characteristic of quiescence. An
      antisense-mediated decrease in c-Myc expression results in decreased cyclin D1
      expression and inhibition of DNA synthesis, mimicking the effects of antiestrogen
      treatment and emphasizing the importance of c-Myc as an estrogen/antiestrogen
      target. These data identify c-Myc, cyclin D1, p21(WAF1/CIP1) and cyclin E-Cdk2 as
      central components of estrogen regulation of cell cycle progression and hence as
      potential downstream targets that contribute to the role of estrogen in
      oncogenesis.

PMID- 12790781
TI  - Oestrogens and prostate cancer.
AB  - Androgens are essential for stimulating normal development, growth and secretory
      activities of the prostate whereas oestrogens are generally regarded as
      inhibitors of growth. Evidence for the local synthesis of oestrogens includes the
      detection of aromatase mRNA and protein in the stroma of human non-malignant
      tissues and in malignant tissue, where it is detected in epithelial tumour cells.
      As well, aromatase activity was measured by biochemical assay and protein was
      detected in prostatic non-malignant and tumour cell lines. Taken together with
      the identification of direct oestrogenic actions on the prostate, these results
      suggest that alterations in local oestrogen synthesis may have significant
      consequences in malignancy of these organs. Genetically modified mouse models
      were studied in order to evaluate the action of oestrogens alone or in
      combination with androgens on the prostate gland. Hypogonadal (hpg) mice are
      deficient in gonadotrophins and androgens but showed direct proliferative
      responses to oestradiol. The responses were characterised by discrete lobe
      specific changes including smooth-muscle regression, fibroblast proliferation,
      inflammation, and basal epithelial cell proliferation and metaplasia. The
      aromatase knockout (ArKO) mouse, deficient in oestrogens due to a non-functional
      aromatase enzyme, developed prostatic hyperplasia during the lifelong exposure to
      elevated androgens, however, no malignant changes were detected in the prostate
      at any time. In contrast, combined androgen and oestrogen treatment has been
      shown to induce prostatic dysplasia and adenocarcinoma. These results demonstrate
      that malignant changes to the prostate gland are dependent upon both androgenic
      and oestrogenic responses and that neither hormone alone is sufficient to evoke
      aberrant patterns of growth, resulting in malignancy.

PMID- 12790782
TI  - The expression and function of estrogen receptor alpha and beta in human breast
      cancer and its clinical application.
AB  - The overexpression of estrogen receptor alpha (ERalpha) is frequently observed in
      the early stage of breast cancer. We previously reported that the specific
      promoter of the ERalpha gene is responsible for this enhanced transcription of
      the gene, and identified the cis-acting elements which play an important role in
      its transcription. Furthermore, methylation of the ERalpha gene promoters also
      contribute to the regulation of gene transcription. Elucidation of these
      mechanisms of ERalpha gene expression may provide useful information for the
      early detection and chemoprevention of breast cancer. On the other hand, the
      expression of ERbeta has been reported in breast cancer. We have also assessed
      the significance and function of ERbeta and its variant types in breast cancer,
      and suggest that ERbeta and ERbetacx specifically suppress the function of
      ERalpha through different mechanisms. ERbeta isoforms may be important functional
      modulators of the estrogen-signaling pathway in breast cancer cells, and might
      affect the clinical outcome of patients. Moreover, to address the role of these
      ERs on the estrogen-dependent growth of breast cancer cells and to develop a
      diagnostic tool, we have analyzed the gene expression profiles of estrogen
      responsive genes using cDNA microarray. Based on these results, the expression of
      several candidate genes in breast cancer tissues were analyzed by real-time RT
      PCR and by immunohistochemical techniques, in order to discover new predictive
      factors for the endocrine therapy of patients with breast cancer. These studies
      could provide new clues for the elucidation of the estrogen-dependent mechanisms
      of cancer and the clinical benefits for patients.

PMID- 12790783
TI  - Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic
      factor for patients with endometrial cancer.
AB  - To clarify whether and how PTEN and the phosphatidylinositol 3-kinase/Akt pathway
      relates to endometrial cancer we examined the expression of these pathway-related
      proteins in patients with endometrial cancer. Of 103 endometrial cancers, 37
      (36%) showed negative immunohistochemical staining for PTEN. Western blotting
      revealed that the level of phosphorylated Akt expression in PTEN-negative cases
      was significantly higher compared with that in positive cases. We found a
      significant inverse correlation between PTEN and phosphorylated Akt. The present
      study indicates the phosphorylation of Akt accompanied by the loss of PTEN in
      clinical specimens of endometrial cancers. In order to investigate the
      relationship between PTEN expression and prognosis in endometrial cancer, 98
      patients with advanced endometrial cancer were newly enrolled. The survival rate
      for PTEN-positive patients was significantly higher than that for PTEN-negative
      or -heterogeneous staining patients. Of the 98 patients, 25 underwent radiation
      therapy, 62 received chemotherapy after surgery, and the remaining 11 did not
      have any postoperative treatment. When patients underwent chemotherapy, the
      survival rate for PTEN-positive cases was clearly higher than that for PTEN
      negative or -heterogeneous cases (62.4 vs 11.8%). Subsequent multivariate
      analysis revealed that PTEN staining was an independent prognostic factor for
      patients undergoing chemotherapy. The current study demonstrates that PTEN
      positive staining is a significant prognostic indicator of favorable survival for
      patients with advanced endometrial cancer who undergo postoperative chemotherapy.

PMID- 12790784
TI  - Androgen receptor involvement in the progression of prostate cancer.
AB  - Since the growth of prostate cancer is androgen-sensitive, metastatic disease has
      been treated by hormonal therapy. Almost all prostate cancer patients initially
      respond to hormonal therapy, but the majority gradually develop resistance. The
      mechanism of the change in tumors from being androgen-responsive to androgen
      unresponsive is generally explained by clonal selection, adaptation, an
      alternative pathway of signal transduction and androgen receptor (AR)
      involvement. Since androgen action is mediated by ARs, abnormalities in ARs are
      believed to play an important role in the progression of prostate cancer.
      Hyperactivated AR gene mutations have been detected in 20-30% of hormone
      refractory tumors and functional analyses have demonstrated a wide responsiveness
      to estrogens, progesterone and anti-androgens as well as to androgens. The AR is
      highly amplified in 30% of patients with hormone-refractory prostate cancer that
      has been treated by castration without anti-androgens. Immunohistochemical
      studies of ARs in hormone-refractory prostate cancer specimens have shown that AR
      protein is down-regulated. DNA hypermethylation of the AR promoter region leading
      to AR down-regulation has been identified in 30% of hormone-refractory prostate
      cancers. The AR N-terminal domain in the LNCaP cell line model is activated by
      interleukin-6 via mitogen-activated protein kinase and single transducers and
      activators of transcription 3. Epidemiological observations have shown that short
      CAG repeats are more frequently associated with higher transactivational function
      in the African-American population, which may explain racial differences in the
      incidence of prostate cancer. Among Japanese, a short CAG repeat appears to
      predict a response to hormonal therapy, indicating a positive prognostic value
      and good prognosis at the metastatic stage of prostate cancer. Several co-factors
      between ARs and the transcriptional complex have been cloned and reports indicate
      that steroid receptor co-activator 1 is correlated with the hormone-refractory
      progression of prostate cancer. Thus, ARs plays an important role in the
      progression of prostate cancer. Based on the findings described above, genetic
      diagnosis and/or molecular-targeted therapy via AR pathways can be developed for
      hormone-refractory states.

PMID- 12790785
TI  - Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen
      receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer
      MCF-7 cell proliferation: a preliminary report.
AB  - LRP16 is a novel gene cloned from lymphocytic cells, and its function is not
      known. The expression level of LRP16 mRNA was up-regulated by estrogen in breast
      cancer MCF-7 cells based on the computed aided serial analysis of gene expression
      (SAGE) analysis. In this study, we investigate the effect of 17beta-estradiol
      (17beta-E(2)) on the expression of LRP16 mRNA and the effects of overexpression
      of LRP16 on the proliferation of cultured MCF-7 cells and the possible mechanisms
      involved. The expression level of LRP16 mRNA induced by 17beta-E(2) was
      determined by Northern blot analysis. LRP16 promoter-controlled luciferase
      expression vector (pGL3-S(0)) was co-transfected with various nuclear receptors,
      including estrogen receptor alpha and beta (ERalpha and ERbeta), glucocorticoid
      receptor alpha (GRalpha), androgen receptor (AR) and peroxisome-proliferator
      activated receptor gamma and alpha (PPARgamma and PPARgamma) into COS-7 cells,
      and the relative luciferase activity was measured using Dual-luciferase report
      assay systems. The effect of overexpression of LRP16 on MCF-7 proliferation was
      examined by the Trypan Blue exclusion method, and the cell cycle was analyzed by
      flow cytometry. The expression levels of cyclin E, p53 and p21(WAF1/CIP1)
      proteins were determined by Western blot analysis. The results showed (1) 17beta
      E(2) induced a five- to eightfold increase in LRP16 mRNA levels in MCF-7 cells;
      (2) the relative luciferase activities in the COS-7 cells co-transfected by pGL3
      S(0) and ERalpha or AR were 7.8-fold and 11-fold respectively of those in the
      control cells transfected by pGL3-S(0) alone; (3) overexpression of LRP16
      stimulated MCF-7 cell proliferation, and the numbers of cells in the S-phase of
      the cell cycle in cells transfected with LRP16 increased about 10% compared with
      the control cells; and (4) cyclin E levels were much higher in cells with
      overexpression of LRP16 than in the control cells, while the expression levels of
      p53 and p21(WAF1/CIP1) were not different between the two groups of cells. From
      these results we concluded that estrogen up-regulates the expression level of
      LRP16 mRNA through activation of ERalpha and that overexpression of LRP16
      promotes MCF-7 cell proliferation probably by increasing cyclin E.

PMID- 12790786
TI  - Prostate cancer susceptibility genes: lessons learned and challenges posed.
AB  - In most developed countries, prostate cancer is the most frequently diagnosed
      malignancy in men. The extent to which the marked racial/ethnic difference in its
      incidence rate is attributable to screening methods, environmental, hormonal
      and/or genetic factors remains unknown. A positive family history is among the
      strongest epidemiological risk factors for prostate cancer. It is now well
      recognized that the role of candidate genetic markers to this multifactorial
      malignancy is more difficult to identify than the identification of other cancer
      susceptibility genes. Indeed, despite the localization of several susceptibility
      loci, there has been limited success in identifying high-risk susceptibility
      genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless,
      three strong candidate susceptibility genes have been described, namely ELAC2
      (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L
      (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1),
      a gene within a region of linkage on chromosome 8p. Additional studies using
      larger cohorts are needed to fully evaluate the role of these susceptibility
      genes in prostate cancer risk. It is also of interest to mention that a
      significant percentage of men with early-onset prostate cancer harbor germline
      mutation in the BRCA2 gene thus confirming its role as a high-risk prostate
      cancer susceptibility gene. Although initial segregation analyses supported the
      hypothesis that a number of rare highly penetrant loci contribute to the
      Mendelian inheritance of prostate cancer, current experimental evidence better
      supports the hypothesis that some of the familial risks may be due to inheritance
      of multiple moderate-risk genetic variants. In this regard, it is not surprising
      that analyses of genes encoding key proteins involved in androgen biosynthesis
      and action led to the observation of a significant association between a
      susceptibility to prostate cancer and common genetic variants in some of those
      genes.

PMID- 12790787
TI  - How to target estrogen receptor-negative breast cancer?
AB  - Estrogen receptor (ER)-positive breast cancers generally have a better prognosis
      and are often responsive to anti-estrogen therapy, which is the first example of
      a successful therapy targeted on a specific protein, the ER. Unfortunately ER
      negative breast cancers are more aggressive and unresponsive to anti-estrogens.
      Other targeted therapies are thus urgently needed, based on breast cancer
      oncogene inhibition or suppressor gene activation as far as molecular studies
      have demonstrated the alteration of expression, or structure of these genes in
      human breast cancer. Using the MDA-MB.231 human breast cancer cell line as a
      model of ER-negative breast cancers, we are investigating two of these approaches
      in our laboratory. Our first approach was to transfect the ER or various ER
      deleted variants into an ER-negative cell line in an attempt to recover anti
      estrogen responsiveness. The unliganded receptor, and surprisingly estradiol,
      were both found to inhibit tumor growth and invasiveness in vitro and in vivo.
      The mechanisms of these inhibitions in ER-negative cancer cells are being
      studied, in an attempt to target the ER sequence responsible for such inhibition
      in these cancer cells. Another strategy is trying to inhibit the activity or
      expression of an oncogene specifically overexpressed in most breast cancers. This
      approach was recently shown by others to be efficient in breast cancer therapy
      with HER2-Neu oncogene amplification using Herceptin. Without excluding other
      molecular putative targets, we have focused our research on cathepsin D as a
      potential target, since it is often overexpressed in aggressive human breast
      cancers, including ER-negative tumors, and rarely associated with HER2-Neu
      amplification. Our first results obtained in vitro on cell lines and in vivo in
      tumor xenografts in nude mice, illustrate that the mode of action of cathepsin D
      in breast cancer is useful to guide the development of these therapies. In the
      past 20 years we have learned that the action of cathepsin D is complex and
      involves both intracellular and extracellular activities due to its proteolytic
      activity and to interactions with membrane components without catalytic activity.
      Each of these mechanisms could be potentially inhibited in an attempt to prevent
      tumor growth. Breast cancer is a very heterogeneous and multigenic disease and
      different targeted therapies adapted to each category of breast cancer are
      therefore required. Validated assays in the primary tumor of molecular markers
      such as ER, HER2-Neu and cathepsin D should help to predict which targeted
      therapy should be applied to cure breast cancer patients.

PMID- 12790788
TI  - New approaches to the understanding of tamoxifen action and resistance.
AB  - Tamoxifen (TAM) provides an effective agent for treatment of hormone-dependent
      breast cancer but resistance uniformly ensues upon continued use. Additional
      studies are required to define more precisely the mechanisms involved in
      development of resistance. We conducted systematic experimental and clinical
      studies based on the hypothesis that tumors exposed to TAM long-term may develop
      resistance by becoming hypersensitive to its estrogenic effects. These
      investigations uncovered new features of the TAM resistance (TR) phenomenon and
      identified possible means for its prevention and/or elimination. Initially we
      confirmed that TR may be divided into two subtypes, primary and acquired
      resistance, and that these differ by certain important characteristics including
      the level of the possible involvement of adaptive and genetic components. Then we
      distinguished at least three consequent stages of this phenomenon: stage I when
      TAM behaves as an antiestrogen, stage II with development of increased
      sensitivity to the agonistic (pro-estrogenic) properties of TAM and stage III
      with an adaptive increase in sensitivity to estradiol (E(2)). During this
      evolutionary process, as shown in vitro, MAP kinase (MAPK) and aromatase
      activities increase. The time frame of the increase in MAPK activity as a rule
      outpaces the increase in aromatase activity during the course of the development
      of TR. This may occur as a response to estrogen deprivation or interruption of
      the process of estrogen signaling and can be one of the promoting factors of
      increased aromatase activation. On the other hand, the chronology of these events
      indicates that changes in the MAPK cascade can be more important for the early
      steps of the development and maintenance of the TR state. Changes in local
      estrogen production/sensitivity to E(2) are perhaps essential for the later steps
      of this phenomenon. We have explored the use of a growth factor-blocking agent to
      abrogate the adaptive changes in sensitivity. Farnesylthiosalicylic acid (FTS),
      an inhibitor of GTP-Ras binding to its membrane acceptor site, reduces the
      increase in the number of MCF-7 cells induced by long-term TAM treatment. It also
      decreases MAPK activity in TAM-treated MCF-7 cells and in established TR cell
      lines. Alone or in combination with letrozole (presumably, through the influence
      on MAPK pathway) FTS exerts moderate inhibitory effects on aromatase activity in
      estrogen-deprived or estrogen-exposed MCF-7 cells. Taken together, our
      observations suggest that FTS is a 'candidate drug' for the treatment of TR. Both
      the adaptive and genetic types of resistance may be amenable to this approach.
      Our studies underline the possible importance of starting the
      treatment/prevention of TR early on. From our clinical studies using
      immunohistochemistry, there is a rather strong rationale to include as a
      predisposing factor in the development of TR the increase in MAPK and aromatase
      activities in human primary breast tumors. In summary, data obtained during the
      course of this project may be considered as evidence supporting the principle
      that processes resulting in responses to TAM as an agonist and the development of
      estrogen hypersensitivity of breast cancer cells could potentially be
      mechanistically linked.

PMID- 12790789
TI  - Endocrine/paracrine/autocrine survival factor activity of bone microenvironment
      participates in the development of androgen ablation and chemotherapy
      refractoriness of prostate cancer metastasis in skeleton.
AB  - Bone is the most frequent site of metastases of prostate cancer and is almost
      always the first and frequently the only site of metastases where disease will
      progress to stage D3. In addition, the number of skeletal metastatic foci is the
      most powerful independent prognostic factor of limited response to hormone
      ablation therapy and poor survival of patients with advanced prostate cancer.
      Furthermore, disease progression frequently occurs in the osteoblastic
      metastases, even though androgen ablation therapy still provides adequate and
      sustained control of disease at the primary site. Notably, the management of
      metastatic disease onto bones has traditionally relied on therapeutic modalities,
      which almost exclusively aim at directly inducing cancer cell death. However,
      accumulating pieces of evidence, from both the clinical and the basic research
      front, point to major limitations of this conventional approach. The in vivo
      response of malignant cells to anticancer therapies is directly influenced by the
      local microenvironment in which they metastasize. In particular, organ sites
      frequently involved in metastatic diseases, such as the bones, appear to confer
      to metastatic cells protection from anticancer drug-induced apoptosis. This
      protection is mediated by soluble growth factors and cytokines released by the
      normal cellular constituents of the host tissue microenvironment. The
      characterization of bone microenvironment-related survival factors has led to the
      development of a novel hormone manipulation which can re-introduce clinical
      responses in patients with stage D3 prostate cancer.

PMID- 12790790
TI  - GnRH antagonists in the treatment of gynecological and breast cancers.
AB  - Approximately 80% of human ovarian and endometrial cancers and 50% of breast
      cancers express GnRH and its receptor as part of an autocrine regulatory system.
      After binding of its ligand the tumor GnRH receptor couples to G-protein alphai
      and activates a variety of intracellular signaling mechanisms. (1) Through
      activation of a protein tyrosine phosphatase, autophosphorylation of growth
      factor receptors is reverted leading to an inhibition of mitogenic signaling and
      reduced cell proliferation. (2) Through activation of nuclear factor kappa B
      antiapoptotic mechanisms are induced protecting tumor cells from apoptosis
      induced, for example, by doxorubicin. (3) Through activation of the Jun kinase
      pathway AP-1 is induced, leading to cell cycle arrest in the G0/G1 phase. It
      seems reasonable to speculate that this system enables the tumor cell to reduce
      proliferation and to activate repair mechanisms while being protected
      simultaneously from apoptosis. Interestingly, GnRH antagonists show the same
      activity in this system as agonists, indicating that the dichotomy GnRH agonist
      GnRH antagonist defined in the pituitary gonadotrope is not valid for the tumor
      GnRH system. Recently, a second type of GnRH receptor, specific for GnRH-II, has
      been identified in ovarian and endometrial cancers, which transmits significantly
      stronger antiproliferative effects than the GnRH-I receptor. GnRH antagonists
      have agonistic effects on this type II receptor. In animal models of human
      cancers, GnRH antagonists had stronger antitumor effects than GnRH agonists.
      Therefore, we performed a phase II clinical trial with the GnRH antagonist,
      cetrorelix (10 mg/day), in patients with ovarian or mullerian carcinoma
      refractory to platinum chemotherapy. Of 17 evaluable patients treated with
      cetrorelix, 3 obtained a partial remission (18%) which lasted for 2 to 6 months.
      Furthermore, 6 patients experienced disease stabilization (35%) for up to 1 year.
      In this very refractory patient population (median number of prior chemotherapies
      = 3) these results are quite remarkable when compared with palliative
      chemotherapy. In addition, cytotoxic GnRH analogs have been developed, where for
      example doxorubicin was covalently coupled to GnRH analogs. These compounds have
      superior antitumor effects in cancers expressing GnRH receptors as compared with
      native doxorubicin and allow for a targeted cytotoxic chemotherapy of gynecologic
      and breast cancers.

PMID- 12790791
TI  - Innate immunity in breast carcinoma.
AB  - The innate immune response, which depends on so-called pattern-recognition
      receptors (PRRs) is an evolutionarily old immune response able to elicit a
      defensive response against a vast array of pathogens. The purpose of this review
      is to revisit the role of innate immunity in breast carcinoma from the oldest
      therapeutic approach using bacillus Calmette-Guerin to the recent findings on the
      manipulation of the PRR pathways with unmethylated cytosine-guanosine
      dinucleotides (CpG motifs). Encouraging results have been obtained in prevention
      and local treatment of murine mammary tumors using tumor cells engineered to
      express stably mycobacterial antigens or directly using CpG-containing
      oligonucleotides. The experimental findings raise the possibility of successful
      anti-tumor management through stimulation of innate immunity in women at high
      risk of developing breast cancer and in breast cancer patients with reasonable
      immunological performance and low tumor load.

PMID- 12790792
TI  - Parathyroid adenomas and cardiovascular risk.
AB  - In recent decades, primary hyperparathyroidism (pHPT) has changed its clinical
      presentation from a disease with bone and renal involvement to a frequently
      asymptomatic disorder detected on routine biochemistry. Nevertheless, it remains
      unclear whether patients with untreated mild asymptomatic hyperparathyroidism are
      at risk for other complications such as increased morbidity and mortality from
      cardiovascular diseases. There are limited data on the incidence of
      cardiovascular abnormalities in mild pHPT. However, pHPT has been associated with
      increased risk of death from cardiovascular disease, hypertension, left
      ventricular hypertrophy (LVH), valvular and myocardial calcifications, impaired
      vascular reactivity, alterations in cardiac conduction, impaired glucose
      metabolism, dyslipidaemia, and alterations in body composition. The nature of
      some of these associations is in question, because cure of pHPT does not lead to
      improvement of the cardiovascular disorder e.g. hypertension. In contrast,
      currently available data suggest that LVH, impaired glucose metabolism and
      dyslipidaemia may improve after surgery and that successful parathyroidectomy
      could decrease the excess mortality in patients with pHPT due to cardiovascular
      disease.

PMID- 12790793
TI  - Epigenetic change in pituitary tumorigenesis.
AB  - Throughout the genome CpG dinucleotides are found at one-fifth of their expected
      frequency and their rarity is further marked by the fact that 70% are methylated.
      In contrast, CpG islands (CGI), found associated with the promoters of many
      genes, have maintained their expected frequency of this dinucleotide, and remain
      unmethylated. Inappropriate methylation of CGIs is associated with histone
      deacetylation and gene silencing, while methylation of CpGs outside of CGIs is
      associated with significantly higher mutation rates. Methylation of CGIs is a
      frequent event in numerous tumour types including those that arise within the
      pituitary gland. Several studies now show highly frequent methylation of the p16
      gene that is significantly associated with loss of cognate protein and that
      appears to be an early change in pituitary tumorigenesis. Collectively, studies
      show that somatotrophinomas are an infrequent target for p16 CGI methylation.
      However, in this pituitary tumour subtype, loss of pRb is associated with either
      CGI methylation or micro-deletion within the protein-pocket binding domain. As in
      other tumour types loss of p16 or RB1 appear to be mutually exclusive events in
      non-functional adenomas and somatotrophinomas respectively. Investigation of the
      Death Associated Protein Kinase gene shows that loss of its protein (DAPK), a pro
      apoptotic molecule, in pituitary tumours is also associated with either
      methylation or deletion within its associated CGI. In the case of DAPK, however,
      these changes segregate with invasive pituitary tumours irrespective of tumour
      subtype. Methylation represents a positive signal that can be detected with
      exquisite sensitivity; in addition, this change targets multiple genes that show
      tumour type specificity. Taken together, the detection of DNA methylation
      changes, using either a panel of predefined marker-islands, or CGI arrays,
      provides the opportunity to generate "methylation profiles". This new knowledge
      will increase our understanding of tumour biology and could ultimately aid
      medical management in these different tumour types, including those of pituitary
      origin.

PMID- 12790794
TI  - Interactions between estrogen and insulin-like growth factor signaling pathways
      in human breast tumor cells.
AB  - Estrogens and insulin-like growth factors (IGFs) act as mitogens promoting cell
      proliferation in normal breast tissue as well as in breast carcinomas. Both
      hormones have been shown to play a role in the development of breast cancer and
      were found to activate multiple signaling pathways leading to proliferation of
      human breast cancer cell lines in vitro. Originally, it was considered that these
      agents manifest their mitogenic actions through separate pathways, but a growing
      body of evidence suggests that the IGF- and estrogen-mediated signaling pathways
      are intertwined. 17beta-Estradiol (E2) has been shown to enhance IGF signaling at
      multiple levels. E2 treatment of breast cancer cells alters expression of nearly
      all of the IGF family members including IGF-I, IGF-II, IGF-binding proteins, IGF
      type I receptor (IGF-RI), and insulin receptor substrate 1. The ligand-bound
      estrogen receptor has been reported to bind to and to activate the IGF-RI
      directly. Vice versa, IGF signaling has been reported to enhance estrogen
      receptor activation in human breast cancer cells by inducing phosphorylation of
      the estrogen receptor. Finally, several groups have described synergistic effects
      of the combination of E2 and IGF-I on S phase entry in breast tumor cell lines.
      Here, we review recent, often contradictory, reports describing the effects of E2
      and IGFs on the proliferation of breast tumor cells, with special emphasis on the
      synergistic effects of the two hormones.

PMID- 12790795
TI  - Bayesian hierarchical approach to estimate insulin sensitivity by minimal model.
AB  - We adopted Bayesian analysis in combination with hierarchical (population)
      modelling to estimate simultaneously population and individual insulin
      sensitivity (SI) and glucose effectiveness (SG) with the minimal model of glucose
      kinetics using data collected during insulin-modified intravenous glucose
      tolerance test (IVGTT) and made comparison with the standard non-linear
      regression analysis. After fasting overnight, subjects with newly presenting Type
      II diabetes according to World Health Organization criteria (n =65; 53 males, 12
      females; age, 54 +/- 9 years; body mass index, 30.4 +/- 5.2 kg/m2; means+/-S.D.)
      underwent IVGTT consisting of a 0.3 g of glucose bolus/kg of body weight given at
      time zero for 2 min, followed by 0.05 unit of insulin/kg of body weight at 20
      min. Bayesian inference was carried out using vague prior distributions and log
      normal distributions to guarantee non-negativity and, thus, physiological
      plausibility of model parameters and associated credible intervals. Bayesian
      analysis gave estimates of SI in all subjects. Non-linear regression analysis
      failed in four cases, where Bayesian analysis-derived SI was located in the lower
      quartile and was estimated with lower precision. The population means of SI and
      SG provided by Bayesian analysis and non-linear regression were identical, but
      the interquartile range given by Bayesian analysis was tighter by approx. 20% for
      SI and by approx. 15% for SG. Individual insulin sensitivities estimated by the
      two methods were highly correlated ( rS=0.98; P <0.001). However, the correlation
      in the lower 20% centile of the insulin-sensitivity range was significantly lower
      than the correlation in the upper 80% centile ( rS=0.71 compared with rS=0.99; P
      <0.001). We conclude that the Bayesian hierarchical analysis is an appealing
      method to estimate SI and SG, as it avoids parameter estimation failures, and
      should be considered when investigating insulin-resistant subjects.

PMID- 12790796
TI  - Mammalian NADH diphosphatases of the Nudix family: cloning and characterization
      of the human peroxisomal NUDT12 protein.
AB  - The human NUDT12 Nudix hydrolase has been expressed in insect cells from a
      baculovirus vector as a His-tagged recombinant protein. In vitro, it efficiently
      hydrolyses NAD(P)H to NMNH and AMP (2',5'-ADP), and diadenosine diphosphate to
      AMP. It also has activity towards NAD(P)(+), ADP-ribose and diadenosine
      triphosphate. K (m) values for NADH, NADPH and NAD(+) are 11, 16 and 190 microM
      and k (cat) values are 11, 16 and 10.5 s(-1) respectively. Thus, like other NADH
      diphosphatases of the Nudix family, NUDT12 has a marked substrate preference for
      the reduced nicotinamide nucleotides. Optimal activity was supported by 50 microM
      Mn(2+) ions in vitro, with 3-fold lower activity at 0.4 mM Mg(2+). Expression of
      NUDT12 as a C-terminal fusion to green fluorescent protein revealed that it was
      targeted to peroxisomes by the C-terminal tripeptide PNL acting as a novel type 1
      peroxisomal targeting signal. Deletion of PNL resulted in diffuse cellular
      fluorescence. In addition, C-terminal, but not N-terminal, fusions with or
      without the PNL signal accumulated in large, unidentified cytoplasmic structures.
      NUDT12 may act to regulate the concentration of peroxisomal nicotinamide
      nucleotide cofactors required for oxidative metabolism in this organelle.

PMID- 12790798
TI  - The renin-angiotensin system and male reproduction: new functions for old
      hormones.
AB  - The blood-borne renin-angiotensin system (RAS) is known best for its role in the
      maintenance of blood pressure and electrolyte and fluid homeostasis. However,
      numerous tIssues show intrinsic angiotensin-generating systems that cater for
      specific local needs through actions that add to, or differ from, the circulating
      RAS. The male reproductive system has several sites of intrinsic RAS activity.
      Recent focus on the epididymis, by our laboratories and by others, has
      contributed important details about the local RAS in this tIssue. The RAS
      components have been localized morphologically and topographically; they have
      been shown to be responsive to androgens and to hypoxia; and angiotensin has been
      shown to influence tubular, and consequently, fluid secretion. Components of the
      RAS have also been found in the testis, vas deferens, prostate and semen.
      Angiotensin II receptors, type 1 and, to a lesser extent, type 2 are widespread,
      and angiotensin IV receptors have been localized in the prostate. The roles of
      the RAS in local processes at these sites are still uncertain and have yet to be
      fully elucidated, although there is evidence for involvement in tubular
      contractility, spermatogenesis, sperm maturation, capacitation, acrosomal
      exocytosis and fertilization. Notwithstanding this evidence for the involvement
      of the RAS in various important aspects of male reproduction, there has so far
      been a lack of clinical evidence, demonstrable by changes in fertility, for a
      crucial role of the RAS in male reproduction. However, it is clear that there are
      several potential targets for manipulating the activity of the male reproductive
      system by interfering with the locally generated angiotensin systems.

PMID- 12790799
TI  - Fatty acid and phorbol ester-mediated interference of mitogenic signaling via
      novel protein kinase C isoforms in pancreatic beta-cells (INS-1).
AB  - It is possible that activation of protein kinase C (PKC) isoforms by free fatty
      acids (FFA) plays a role in the failure of pancreatic beta-cell mass expansion to
      compensate for peripheral insulin resistance in the pathogenesis of type-2
      diabetes. The effect of lipid moieties on activation of conventional (PKC-alpha
      and -beta1), novel (PKC-delta) and atypical (PKC-zeta) PKC isoforms was evaluated
      in an in vitro assay, using biotinylated neurogranin as a substrate. Oleoyl
      Coenzyme A (CoA) and palmitoyl-CoA, but not unesterified FFA, significantly
      increased the activity of all PKC isoforms (P< or =0.05), particularly that for
      PKC-delta. It was found that FFA (0.4 mM oleate/complexed to 0.5% bovine serum
      albumin) inhibited IGF-I-induced activation of protein kinase B (PKB) in the
      pancreatic beta-cell line (INS-1), but this was alleviated in the presence of the
      general PKC inhibitor (Go6850; 1 microM). To further investigate whether
      conventional or novel PKC isoforms adversely affect beta-cell proliferation, the
      effect of phorbol ester (phorbol 12-myristate 13-acetate; PMA)-mediated
      activation of these PKC isoforms on glucose/IGF-I-induced INS-1 cell mitogenesis,
      and insulin receptor substrate (IRS)-mediated signal transduction was
      investigated. PMA-mediated activation of PKC (100 nM; 4 h) reduced glucose/IGF-I
      mediated beta-cell mitogenesis (>50%; P< or =0.05), which was reversible by the
      general PKC inhibitor Go6850 (1 microM), indicating an effect of PKC and not due
      to a non-specific PMA toxicity. PMA inhibited IGF-I-induced activation of PKB,
      correlating with inhibition of IGF-I-induced association of IRS-2 with the p85
      regulatory subunit of phosphatidylinositol-3 kinase. However, in contrast, PMA
      activated the mitogen-activated protein kinases, Erk1/2. Titration inhibition
      analysis using PKC isoform inhibitors indicated that these PMA-induced effects
      were via novel PKC isoforms. Thus, FFA/PMA-induced activation of novel PKC
      isoforms can inhibit glucose/IGF-I-mediated beta-cell mitogenesis, in part by
      decreasing PKB activation, despite an upregulation of Erk1/2. Thus, activation of
      novel PKC isoforms by long-chain acyl-CoA may well contribute to decreasing beta
      cell mass in the pathogenesis of type-2 diabetes, similar to their inhibition of
      insulin signal transduction which causes insulin resistance.

PMID- 12790800
TI  - Inhibition of Src tyrosine kinase stimulates adrenal androgen production.
AB  - A unique characteristic of the primate adrenal is the ability to produce 19
      carbon steroids, often called the adrenal androgens. Although it is clear that
      the major human adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate
      (DHEA-S), are produced almost solely in the adrenal reticularis, the mechanisms
      regulating production are poorly understood. Herein, we tested the hypothesis
      that the Src family of tyrosine kinases are involved in the regulation of adrenal
      androgen production. The NCI-H295R human adrenal cell line and primary human
      adrenal cells in culture were used to study adrenal androgen production and
      expression of enzymes involved in steroidogenesis. To examine the role of Src
      tyrosine kinase, cells were treated with PP2, a specific Src inhibitor.
      Alternatively, adrenal cells were transfected with an expression vector
      containing a dominant-negative form of Src. PP2 treatment inhibited basal
      cortisol production while significantly increasing the production of DHEA and
      DHEA-S (together referred to as DHEA(S)) in both adrenal cell models. The effect
      of PP2 on steroidogenesis occurred along with a rapid induction of steroidogenic
      acute regulatory (StAR) protein synthesis as revealed by Western analysis.
      Treatment with PP2 also increased mRNA levels for StAR, and cholesterol side
      chain cleavage (CYP11A) and 17alpha-hydroxylase/17,20-lyase (CYP17) enzymes.
      Treatment of adrenal cells with the cAMP agonist dibutyryladenosine cyclic
      monophosphate (dbcAMP), stimulated the production of cortisol and DHEA(S).
      However, treatment of adrenal cells with a combination of PP2 and dbcAMP enhanced
      the production of DHEA(S) while inhibiting cortisol production. During dbcAMP
      treatment PP2 was able to augment the expression of CYP17 and to inhibit the
      induction of 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) levels.
      Increasing the CYP17 to HSD3B2 ratio is likely to promote the use of steroid
      precursors for the production of DHEA(S) and not for cortisol. Taken together
      these data suggest that the inhibition of Src tyrosine kinases causes adrenal
      cells to adopt a reticularis phenotype both by the production of DHEA(S) and by
      the steroidogenic enzymes expressed.

PMID- 12790801
TI  - Expression of estrogen, progesterone and androgen receptors in the oviduct of
      developing, cycling and pre-implantation rats.
AB  - To determine expression and localization of receptors for estrogen (ER),
      progesterone (PR) and androgen (AR), detailed immunohistochemical evaluations
      were performed in the Sprague-Dawley rat oviduct during pre- and neonatal
      development, estrous cycle and pre-implantation period. In addition, real-time RT
      PCR studies were conducted to evaluate changes in ERalpha, ERbeta, total PR (PR
      A+B), PR-B and AR mRNA expressions. All receptors except for ERbeta were detected
      in epithelial, and stromal or mesenchymal cells of the fetal and neonatal
      oviduct, and increased with development. During the estrous cycle and early
      pregnancy, ERalpha and PR-A+B were expressed in epithelial, stromal and muscle
      cells throughout the oviduct region, and showed changes in expression
      predominantly in the isthmus. Only a few epithelial cells in the infundibulum
      (inf) and ampulla (AMP) showed ERbeta staining. AR was detected in stromal and
      muscle cells throughout the oviduct region, and in epithelial cells of the
      inf/AMP. Taken together, ERalpha, PR-A+B and AR were detected in the epithelium
      of the inf/AMP region, but all of these receptors were expressed in a distinct
      subset of epithelial cells which were negative for beta-tubulin IV, a ciliated
      epithelial cell marker. These results contribute to a better understanding of the
      respective roles of ERs, PRs and AR in the rat oviduct.

PMID- 12790802
TI  - Identification of hepatic transcriptional changes in insulin-resistant rats
      treated with peroxisome proliferator activated receptor-alpha agonists.
AB  - Peroxisome proliferator activated receptor (PPAR)-alpha controls the expression
      of multiple genes involved in lipid metabolism, and activators of PPAR-alpha,
      such as fibrates, are commonly used drugs in the treatment of
      hypertriglyceridemia and other dyslipidemic states. Recent data have also
      suggested a role for PPAR-alpha in insulin resistance and glucose homeostasis. In
      the present study, we have assessed the transcriptional and physiological
      responses to PPAR-alpha activation in a diet-induced rat model of insulin
      resistance. The two PPAR-alpha activators, fenofibrate and Wy-14643, were dosed
      at different concentrations in high-fat fed Sprague-Dawley rats, and the
      transcriptional responses were examined in liver using cDNA microarrays. In these
      analyses, 98 genes were identified as being regulated by both compounds. From
      this pool of genes, 27 correlated to the observed effect on plasma insulin,
      including PPAR-alpha itself and the leukocyte antigen-related protein tyrosine
      phosphatase (PTP-LAR). PTP-LAR was downregulated by both compounds, and showed
      upregulation as a result of the high-fat feeding. This regulation was also
      observed at the protein level. Furthermore, downregulation of PTP-LAR by
      fenofibric acid was demonstrated in rat FaO hepatoma cells in vitro, indicating
      that the observed regulation of PTP-LAR by fenofibrate and Wy-14643 in vivo is
      mediated as a direct effect of the PPAR agonists on the hepatocytes. PTP-LAR is
      one of the first genes involved in insulin receptor signaling to be shown to be
      regulated by PPAR-alpha agonists. These data suggest that factors apart from
      skeletal muscle lipid supply may influence PPAR-alpha-mediated amelioration of
      insulin resistance.

PMID- 12790803
TI  - Tetracycline-regulated secretion of human insulin in a transfected non-endocrine
      cell line.
AB  - Long-term constitutive secretion of insulin by implantation of ex vivo
      transfected cells such as fibroblasts or myoblasts or in situ by intramuscular
      injection of naked plasmid DNA provides a potential approach to gene therapy for
      diabetes mellitus. A mechanism for regulating insulin secretion will be necessary
      to realize the therapeutic potential of this approach. A second obstacle is the
      inability of non-endocrine host cells to fully process proinsulin. Therefore,
      alteration of the wild-type cDNA will be necessary to achieve processing of
      proinsulin by endogenous endoproteases within these cells. The cDNAs for beta
      galactosidase (beta), human wild-type proinsulin (hppI1) and a mutated construct
      (hppI4), in which the dibasic PC2 and PC3 cleavage sites had been altered to form
      furin cleavage sites, were sub-cloned into four vectors (pCR3, pVR1012, pIRES,
      pTRE), including a tetracycline responsive plasmid (pTRE) that requires co
      transfection with another plasmid encoding a transactivator (pTet-off) for
      transgene expression. Transient transfection of the COS-7 fibroblast cell line
      with these constructs was performed using DEAE-dextran and liposomes. Analysis of
      vector efficiencies revealed that pTRE/pTet-off>pIRES>pCR3>pVR1012. Further
      analysis demonstrated total pro/insulin secretion of 2.33 ng/10(6) cells/24 h
      with > or =25% processed to insulin in hppI-1.pTRE/pTet-off-transfected cells
      compared with 0.39 ng/10(6) cells/24 h and >70% processing in hppI-4.pTRE/pTet
      off-transfected cells. In co-transfection studies with pTRE-hppI1/pTet-off and
      pTRE-hppI4/pTet-off constructs, pro/insulin secretion was inhibited to 65-66% and
      36-38% of control (100%) in the presence of 0.01 and 0.1 microg/ml tetracycline
      respectively over a 24-h incubation period. Furthermore, reversal of tetracycline
      inhibition was demonstrated for pTRE-hppI1/pTet-off- and pTRE-hppI4/pTet-off
      transfected cells. After a 48-h incubation with 1.0 microg/ml tetracycline, total
      pro/insulin levels were 10 and 14% compared with untreated cells respectively. On
      tetracycline removal, total proinsulin levels increased and were equivalent to
      untreated groups 72 h later. In conclusion, regulation of fully processed human
      insulin secretion has been achieved in a transiently transfected non-endocrine
      cell line.

PMID- 12790797
TI  - Mechanisms of cross-talk between G-protein-coupled receptors resulting in
      enhanced release of intracellular Ca2+.
AB  - Alteration in [Ca(2+)](i) (the intracellular concentration of Ca(2+)) is a key
      regulator of many cellular processes. To allow precise regulation of [Ca(2+)](i)
      and a diversity of signalling by this ion, cells possess many mechanisms by which
      they are able to control [Ca(2+)](i) both globally and at the subcellular level.
      Among these are many members of the superfamily of GPCRs (G-protein-coupled
      receptors), which are characterized by the presence of seven transmembrane
      domains. Typically, those receptors able to activate PLC (phospholipase C)
      enzymes cause release of Ca(2+) from intracellular stores and influence Ca(2+)
      entry across the plasma membrane. It has been well documented that Ca(2+)
      signalling by one type of GPCR can be influenced by stimulation of a different
      type of GPCR. Indeed, many studies have demonstrated heterologous desensitization
      between two different PLC-coupled GPCRs. This is not surprising, given our
      current understanding of negative-feedback regulation and the likely shared
      components of the signalling pathway. However, there are also many documented
      examples of interactions between GPCRs, often coupling preferentially to
      different signalling pathways, which result in a potentiation of Ca(2+)
      signalling. Such interactions have important implications for both the control of
      cell function and the interpretation of in vitro cell-based assays. However,
      there is currently no single mechanism that adequately accounts for all examples
      of this type of cross-talk. Indeed, many studies either have not addressed this
      issue or have been unable to determine the mechanism(s) involved. This review
      seeks to explore a range of possible mechanisms to convey their potential
      diversity and to provide a basis for further experimental investigation.

PMID- 12790804
TI  - Analysis of temporal changes in the expression of estrogen-regulated genes in the
      uterus.
AB  - In order to understand early events caused by estrogen in vivo, temporal uterine
      gene expression profiles at early stages were examined using DNA microarray
      analysis. Ovariectomized mice were exposed to 17beta-estradiol and the temporal
      mRNA expression changes of ten thousand various genes were analyzed. Clustering
      analysis revealed that there are at least two phases of gene activation during
      the period up to six hours. One involved immediate-early genes, which included
      certain transcription factors and growth factors as well as oncogenes. The other
      involved early-late genes, which included genes related to RNA and protein
      synthesis. In clusters of down-regulated genes, transcription factors, proteases,
      apoptosis and cell cycle genes were found. These hormone-inducible genes were not
      induced in estrogen receptor (ER) alpha knockout mice. Although expression of
      ERbeta is known in the uterus, these findings indicate the importance of ERalpha
      in the changes in gene expression in the uterus.

PMID- 12790805
TI  - Identification of a functional glucocorticoid response element in the promoter of
      the cyclin-dependent kinase inhibitor p57Kip2.
AB  - Glucocorticoids are known regulators of the cell cycle, normally exerting an anti
      proliferative effect. We have previously shown that glucocorticoids stimulate
      expression of p57(Kip2), a member of the Cip/Kip family of cyclin-dependent
      kinase inhibitors which, in some cell types, may account for the anti
      proliferative responses seen after glucocorticoid treatment. The induction of
      p57(Kip2) involves primary transcriptional effects where no de novo protein
      synthesis is necessary, suggesting a direct interaction of the glucocorticoid
      receptor with the p57(Kip2) gene. In this study we have identified a functional
      glucocorticoid response element (GRE), located 5 kilo bases (kb) upstream of the
      transcription start site in the human p57(Kip2) promoter. This GRE was functional
      also when isolated, suggesting a direct transcriptional effect of the
      glucocorticoid receptor. Furthermore, mutation of this GRE abolished
      glucocorticoid induction of the reporter gene, whereas mutation of a nearby Sp1
      site did not. Using electrophoretic mobility shift assays, we have shown that the
      -5 kb p57(Kip2) promoter GRE was able to compete with a well-known GRE for
      glucocorticoid receptor binding. Sequence comparisons with the mouse genome
      showed that this GRE is highly conserved, further strengthening the biological
      importance of this site. All these data emphasize the involvement of this GRE in
      the glucocorticoid-mediated induction of p57(Kip2) expression.

PMID- 12790806
TI  - Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye
      diseases ex vivo and indicates adipogenesis in progress in vivo.
AB  - The thyrotrophin receptor (TSHR) provides an autoantigenic link between the
      thyroid and orbit in Graves' (GD) and thyroid eye diseases (TED). We measured
      TSHR transcripts in different fat depots to determine whether TSHR expression
      levels are influenced by the autoimmune/inflammatory process and/or thyroid
      hormone status, using quantitative real-time PCR. Nine intact or fractionated
      adipose samples, from patients with GD and/or TED, were analysed ex vivo. Eight
      expressed the TSHR, at levels approaching the thyroid, and one was at the limit
      of detection. Thirteen/fifteen orbital and abdominal fat samples from patients
      free of GD and TED, measured ex vivo, were negative for TSHR transcripts and two
      were at the limit of detection. All preadipocyte samples induced to differentiate
      in vitro expressed the TSHR. To investigate the influence of thyroid hormone
      status on adipose TSHR expression, we induced hyper- and hypothyroidism in BALBc
      mice by administering tri-iodothyronine and propylthiouracil respectively. In
      euthyroid animals, whole fat samples were at the limit of detection and were not
      altered by thyroid hormone status. The results show that adipose TSHR expression
      ex vivo indicates adipogenesis in progress in vivo and is associated with the
      autoimmune/inflammatory process in GD and TED but is not restricted to the orbit
      or influenced by thyroid hormone status.

PMID- 12790808
TI  - The expression of the sarco/endoplasmic reticulum Ca2+-ATPases in thyroid and its
      down-regulation following neoplastic transformation.
AB  - Maintaining a high Ca(2+) concentration in the lumen of the endoplasmic reticulum
      (ER), by the action of sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs), is
      important in many cellular processes, such as Ca(2+)-mediated cytosolic signaling
      in response to extracellular stimuli, cell growth and proliferation, and
      synthesis, processing and folding of ER-translated proteins. In the thyroid
      gland, SERCAs have not been studied yet, and there is little information
      available on general problems such as the expression of SERCAs following
      neoplastic transformation. In this study we investigated the expression of
      SERCA2b and SERCA3 in rat thyroid tIssue and, in addition, in normal and
      transformed rat thyroid cell lines. RT-PCR and Northern blot assays showed that
      SERCA2b is the SERCA form preferentially expressed in the thyroid. In rat
      thyroid, SERCA2b mRNA was expressed at a higher level than that of other non
      muscle tIssues such as liver or spleen, but at much lower level than in brain. On
      the other hand, SERCA3 mRNA was not detected in thyroid by Northern blot
      analysis, or barely detected by RT-PCR assays. We also studied the SERCA2b
      expression pattern in PC Cl3 thyroid cells transformed by several oncogenes that
      induce different degrees of malignancy and dedifferentiation. RT-PCR and Northern
      blot assays showed that SERCA2b mRNA expression dramatically decreased in highly
      tumorigenic thyroid cells, while expression of glyceraldehyde-3-phosphate
      dehydrogenase mRNA, a housekeeping gene used as internal control, exhibited no
      variations. The dramatic down-regulation of SERCA2b expression in fully
      transformed thyroid cells was also evident by Western blot analysis. Also,
      following neoplastic transformation of thyroid cells, the enzymatic activity of
      SERCA2b was reduced in a measure which correlated with the mRNA and protein
      levels. Therefore, rat thyrocytes expressed intermediate levels of SERCAs, mostly
      the SERCA2b isoform. This pattern of expression was basically reproduced in fully
      differentiated thyroid cells in culture and was sensitive to neoplastic
      transformation.

PMID- 12790807
TI  - Transcriptional regulation of the mouse steroidogenic acute regulatory protein
      gene by the cAMP response-element binding protein and steroidogenic factor 1.
AB  - Transcriptional induction by cAMP is mediated through the interaction of the cAMP
      response-element binding protein (CREB) with a cAMP response element (CRE) in the
      promoter of target genes. The steroidogenic acute regulatory (StAR) protein gene
      is regulated by cAMP-mediated signaling in steroidogenic cells even though its
      promoter lacks a consensus CRE. Previously, we have identified three highly
      conserved 5'-CRE half-sites within the -96/-67 bp region of the mouse StAR gene,
      and a member of the CREB family (CREB/CRE modulator (CREM)) was shown to be
      involved in its expression and regulation. Here we show that CREB and CREMtau
      (but not CREMalpha and CREMbeta) have qualitatively similar effects on StAR
      promoter activity in response to (Bu)(2)cAMP. Studies on the effects of the
      functional integrity of the CRE half-sites on CREB-dependent (Bu)(2)cAMP-mediated
      StAR gene transcription demonstrated the greater importance of the CRE2 site in
      comparison with the CRE1 and CRE3 sites. The CRE2 sequence was also found to bind
      specifically to recombinant CREB protein and nuclear extract from MA-10 mouse
      Leydig tumor cells. The cAMP and CREB/CREM responsive region (-151/-1 bp) of the
      mouse StAR promoter also contains three recognition motifs for steroidogenic
      factor 1 (SF-1). Electrophoretic mobility shift assays and reporter gene analyses
      demonstrated the involvement of different SF-1 elements in StAR gene expression
      with the order of importance being SF-1/3>SF-1/1>SF-1/2. Specific mutations that
      eliminated the binding sites of CRE and SF-1 elements, either alone or in
      combination, resulted in an attenuation of StAR promoter activity, indicating
      that CREB and SF-1 can regulate StAR gene transcription in a cooperative fashion.
      In addition, mammalian two-hybrid assays revealed a high affinity protein-protein
      interaction between CREB/CREMtau and SF-1 which appeared to be dependent upon
      CREB protein phosphorylation. These findings further demonstrate CREB's role in
      StAR gene transcription and also provide evidence that the combined action of
      CREB/CREMtau and SF-1 results in enhanced activation of the StAR promoter.

PMID- 12790810
TI  - Anaesthesia for patients with Creutzfeldt-Jakob disease. A practical guide.

PMID- 12790809
TI  - Transcriptional activation by estrogen receptor (ERalpha) and steroid receptor
      coactivator (SRC1) involves distinct mechanisms in yeast and mammalian cells.
AB  - Steroid receptors activate transcription in yeast cells via interactions with
      endogenous coactivators and/or basal factors. We examined the effects of
      mutations in the ligand binding domain on the transcriptional activity of ERalpha
      in yeast. Our results show that mutations in Helix 3 (K366A) and Helix 12 (M547A,
      L548A) disrupt transcriptional activity of ERalpha in yeast, as previously
      observed in mammalian cells. However, replacement of a conserved tyrosine residue
      in Helix 12 with alanine or aspartate (Y541A and Y541D), which renders ERalpha
      constitutively active in mammalian cells, had only a weak stimulatory effect on
      ligand-independent reporter activation by ERalpha in yeast. Two-hybrid
      interaction experiments revealed that a Y541A mutant expressed in yeast was
      capable of ligand-independent binding to a mammalian coactivator, suggesting that
      there is a subtle difference in how this mutant interacts with mammalian and
      yeast cofactors. We also show that the ligand-dependent activities of ERalpha and
      progesterone receptor (PR) in yeast cells were strongly enhanced by the human
      p160 protein steroid receptor coactivator (SRC1), but not by CREB-Binding Protein
      (CBP) or the p300/CBP associated factor (P/CAF). Although the SRC1 activation
      domains AD1 and AD2 are functional in yeast, deletion of these sequences only
      partially impaired SRC1 coactivator function in this organism; this is in
      contrast to similar experiments in mammalian cells. Thus SRC1 sequences involved
      in recruitment of CBP/p300 and Co-Activator-Associated Arginine Methyltransferase
      (CARM-1) in mammalian cells are not essential for its function in yeast,
      suggesting that SRC1 operates via distinct mechanisms in yeast and mammalian
      cells.

PMID- 12790811
TI  - Evaluation of personal, environmental and biological exposure of paediatric
      anaesthetists to nitrous oxide and sevoflurane.
AB  - Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic
      gases, which often exceed set safety limits. Recommended personal diffusive
      sampling techniques for monitoring exposure to waste anaesthetic gases may not
      give a true profile of exposure and hence biological sampling may also be
      necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide
      and sevoflurane as assessed by personal environmental and biological samples. The
      influence of venue and technique, and the strength of the relationship among the
      various sampling techniques were analysed. The study found that exposure to
      nitrous oxide during paediatric anaesthetic inductions is still a major problem,
      although exposure to sevoflurane was usually within the accepted limits. The type
      of breathing system used and the presence of scavenging seem to influence this
      exposure, though surprisingly, the induction technique or the methods of airway
      control do not. No significant relationship was found between the various
      biological indicators measured.

PMID- 12790812
TI  - Long-term survival following intensive care: subgroup analysis and comparison
      with the general population.
AB  - This study aimed to compare the very long-term survival of critically ill
      patients with that of the general population, and examine the association among
      age, sex, admission diagnosis, APACHE II score and mortality. In a retrospective
      observational cohort study of prospectively gathered data, 2104 adult patients
      admitted to the intensive care unit (ICU) of a teaching hospital in Glasgow from
      1985 to 1992, were followed until 1997. Vital status at five years was compared
      with that of an age- and sex-matched Scottish population. Five-year mortality for
      the ICU patients was 47.1%, 3.4 times higher than that of the general population.
      For those surviving intensive care the five-year mortality was 33.4%. Mortality
      was greater than that of the general population for four years following
      intensive care unit admission (95% confidence interval included 1.0 at four
      years). Multivariate analysis showed that risk factors for mortality in those
      admitted to ICU were age, APACHE II score on admission and diagnostic category.
      Mortality was higher for those admitted with haematological (87.5%) and
      neurological diseases (61.7%) and septic shock (62.9%). A risk score was
      produced: Risk Score = 10 (age hazard ratio + APACHE II hazard ratio + diagnosis
      hazard ratio). None of the patients with a risk score > 100 survived more than
      five years and for those who survived to five years the mean risk score was 57.
      Long-term survival following intensive care is not only related to age and
      severity of illness but also diagnostic category. The risk of mortality in
      survivors of critical illness matches that of the normal population after four
      years. Age, severity of illness and diagnosis can be combined to provide an
      estimate of five-year survival.

PMID- 12790813
TI  - Effect of milrinone on vecuronium-induced neuromuscular block.
AB  - We examined the effect of milrinone, a phosphodiesterase III inhibitor, on
      neuromuscular block induced by vecuronium. Thirty adult patients were randomly
      assigned to one of two equal groups: the milrinone group and the control group.
      Subjects in the milrinone group received an intravenous loading dose of milrinone
      5 microg x kg-1x min-1 for 10 min, followed by an infusion at a rate of 0.5
      microg x kg-1x min-1. Subjects in the control group received normal saline at a
      rate of 0.1 ml x kg-1 x h-1. Thirty minutes after the beginning of the infusion
      of milrinone, anaesthesia was induced with intravenous thiopental 4 mg x kg-1 and
      fentanyl 2 microg x kg-1, and was maintained with isoflurane in oxygen and
      nitrous oxide. Neuromuscular blockade was monitored electromyographically at the
      adductor pollicis muscle. The times from the administration of vecuronium 0.1
      mg.kg-1 to the onset of neuromuscular block and the return of the first, second,
      third, and fourth response of the train-of-four were compared between the two
      groups. Times to the recovery of the ratio of the first twitch to the control
      twitch to 25%, 50% and 75%, and times to the recovery of train-of-four ratio to
      25%, 50% and 75% were also compared between the two groups. The onset of
      neuromuscular block in the milrinone group was significantly slower than in the
      control group. The times to the returns of the four twitches of the train-of
      four, times to recovery of the ratio of the first twitch to the control twitch to
      25% and 50%, and the times to the recovery of the train-of-four ratio to 25% and
      50% were significantly shorter in the milrinone group than in the control group.
      We conclude that milrinone delays the onset of neuromuscular blockade but hastens
      its recovery in anaesthetised patients receiving vecuronium.

PMID- 12790814
TI  - New aspects of ventilation in acute lung injury.
AB  - Recent recognition that artificial ventilation may cause damage to the acutely
      injured lung has caused renewed interest in ventilation techniques that minimise
      this potential harm. Many ventilation techniques have proved beneficial in small
      trials of very specific patient groups, but most have subsequently failed to
      translate into improved patient outcome in larger trials. An exception to this is
      'protective ventilation' using reduced tidal volumes (to lower airway pressure)
      and increased PEEP (to reduce pulmonary collapse). Results of trials of
      protective ventilation have been encouraging, and the technique should now be
      adopted more widely. High frequency ventilation, inverse ratio ventilation, prone
      positioning and inhaled nitric oxide are all techniques that may be considered
      when, in spite of optimal artificial ventilation, the patient's gas exchange
      remains dangerously poor. Under these circumstances, the choice of technique is
      dependent on their availability, local expertise and individual patient needs.

PMID- 12790815
TI  - Startin's pneumatic inhaler.
AB  - This apparatus was seen by one of us (DAW) in a private collection. Although it
      was one of the first ether inhalers to be manufactured commercially, and was
      described in the medical literature of the time, it is not mentioned in any of
      the histories of anaesthesia. Its genesis was unusual, and it presents a number
      of interesting features, not least being the purpose for which it was originally
      designed.

PMID- 12790816
TI  - The rigid nasendoscope as a tool for difficult tracheal intubation: a manikin
      study.
AB  - We examined the use of the 30 degrees rigid nasendoscope in aiding difficult
      tracheal intubations. A Cormack and Lehane grade 4 difficult intubation (no view
      of glottis or epiglottis) was set up on a manikin. After 10 s of tuition, 40
      anaesthetists attempted to pass a standard gum elastic bougie between the cords,
      with and without the nasendoscope, in randomised order. A bougie curved to an
      'optimal curve' was also tested. Using the standard bougie 13/40 (33%) passed the
      bougie between the cords without the nasendoscope, compared with 31/40 (78%) when
      using the nasendoscope (p < 0.001). The 'optimal curve' bougie resulted in 29/40
      (73%) and 39/40 (98%) success rates without and with the nasendoscope,
      respectively (p = 0.004). The nasendoscope is a simple and easy to use tool in
      grade 4 intubation, and results are improved further by the use of an 'optimal
      curve' bougie.

PMID- 12790817
TI  - Rapidly repeated intravenous boluses of salbutamol for acute severe asthma.
AB  - We describe the use of intravenous boluses of salbutamol given rapidly (over 1-2
      min) in children (5 microg x kg-1) and young adults (250 microg) with acute
      severe asthma who were not improving with doses of nebulised salbutamol.
      Intravenous boluses were repeated within a short time until improvement was seen.
      Two of the seven patients required tracheal intubation and ventilation.

PMID- 12790818
TI  - Postoperative analgesia following renal transplantation - current practice in the
      UK.

PMID- 12790819
TI  - Syringe labelling in critical care areas.

PMID- 12790820
TI  - Failed gastric tube insertion with the ProSeal laryngeal mask airway (PLMA).

PMID- 12790821
TI  - Retropharyngeal abscess presenting with upper airway obstruction.

PMID- 12790822
TI  - To refuse or not to refuse, that is the question?

PMID- 12790823
TI  - Another central line complication: failure of inotrope delivery due to equipment
      incompatibility.

PMID- 12790824
TI  - Fibreoptic equipment and variant Creutzfeldt-Jakob disease.

PMID- 12790825
TI  - Transient lingual ischaemia during anaesthesia.

PMID- 12790826
TI  - Bronchospasm or blocked tracheal tube?

PMID- 12790827
TI  - Consenting for direct laryngoscopy.

PMID- 12790828
TI  - Expiratory obstruction caused by inappropriate connection of the expiratory limb
      of a breathing circuit.

PMID- 12790829
TI  - Total intravenous anaesthesia for oculoplastic surgery in a patient with
      myasthenia gravis without high-dependency care.

PMID- 12790830
TI  - Anterior commissure laryngoscope.

PMID- 12790831
TI  - The oesophageal tracheal combitube: a pilot study on airflow resistance and
      ventilatory pressures in 26 anaesthetised patients.

PMID- 12790832
TI  - Giant axonal neuropathy and anaesthesia.

PMID- 12790834
TI  - Problems performing a sciatic nerve block in an amputee.

PMID- 12790835
TI  - Difficult central venous access - another role for the portable Doppler device
      (Dopplex).

PMID- 12790833
TI  - Dystonic reactions to cyclizine.

PMID- 12790836
TI  - Anaesthetised for evacuation of retained products of conception; delivered a baby
      instead.

PMID- 12790837
TI  - Pulse oximeter ear probe.

PMID- 12790838
TI  - Repeated courses of antenatal corticosteroids: is it justified?
AB  - The benefits of a single course of antenatal corticosteroids on neonatal outcomes
      are well established. There is, however, much controversy about how long this
      treatment should continue, and whether repeated courses should be administered if
      the women remain at risk for preterm delivery 7 days after the initial therapy.
      This review aims to discuss current evidence on the effectiveness and safety of
      repeated courses of antenatal corticosteroids.

PMID- 12790839
TI  - Serum levels of macrophage colony-stimulating factor after cesarean section,
      vaginal delivery, or laparotomy in normal pregnant women and gynecologic
      patients.
AB  - BACKGROUND: Macrophage colony-stimulating factor (M-CSF) is located in villous
      cells lining the vessels in the placenta in the third trimester and has been
      implicated in placental growth and development. Macrophage colony-stimulating
      factor levels in peripheral blood increased significantly with progression of
      pregnancy in uncomplicated pregnancies. The serum levels of M-CSF appear to be
      altered after laparotomy in normal pregnant women and nonpregnant gynecologic
      patients. Thus, the present study examined changes in serum levels of M-CSF
      before and after laparotomy and compared these findings between the two groups.
      Macrophage colony-stimulating factor levels before and after vaginal delivery
      were also examined. METHODS: Peripheral blood was collected before, 1 day, and 10
      days after laparotomy or vaginal delivery from 38 subjects, of whom 14 were
      normal pregnant women who underwent cesarean section (group 1), 12 were
      gynecologic patients (group 2), and 12 were normal pregnant women who delivered
      vaginally (group 3). The M-CSF level was determined by the sandwich ELISA method
      using three antibodies. RESULTS: In all groups, the serum levels of M-CSF
      increased significantly 1 day after laparotomy or vaginal delivery, but then
      decreased significantly after 10 days. The net increase 1 day after laparotomy
      was significantly lower in group 1 than in group 2. Before and 1 day after
      laparotomy, the M-CSF levels were significantly higher in group 1 than in group
      2, but not 10 days after laparotomy. Changes in M-CSF levels in group 3 were
      relatively similar to those in group 1. CONCLUSIONS: Serum levels of M-CSF were
      significantly higher in groups 1 and 3 than in group 2, before laparotomy or
      vaginal delivery. The M-CSF level increased moderately 1 day after cesarean or
      vaginal delivery, and it increased remarkably after gynecologic laparotomy. The
      increases in M-CSF levels postlaparotomy may occur via different mechanisms
      between groups 1 and 2. Placental removal and termination of pregnancy might
      contribute to the decrease in M-CSF levels, leading to only a moderate increase
      in M-CSF levels 1 day after laparotomy in group 1.

PMID- 12790840
TI  - Differential expression of T-helper cytokines in the peritoneal fluid of women
      with normal ovarian cycle compared with women with chronic anovulation.
AB  - BACKGROUND: Estrogen and progesterone immunoregulate the genital environment by
      expression of cytokines and growth factors. OBJECTIVE: To investigate the pattern
      of expression of T-helper cytokines during the ovarian cycle compared with women
      with chronic anovulation resistant to clomiphene citrate. HYPOTHESIS: Expression
      of T-helper cytokines in women with chronic anovulation may be different from the
      pattern in women with a normal ovarian cycle. METHODS: We evaluated 31 infertile
      women having laparoscopy for evaluation of tubal patency and evidence of
      ovulation in two groups during (a) the luteal phase (17 women) and (b) the
      follicular phase (14 women). A third group was composed of 14 women with
      polycystic ovarian syndrome, but they were resistant to clomiphene citrate for
      induction of ovulation and had laparoscopic ovarian cautery. Peritoneal fluid was
      collected during laparoscopy. Estimation of T-helper cytokine interleukin (IL)-2,
      tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 in serum, peritoneal fluid and
      culture of the peritoneal mononuclear cells was performed by ELISA. Serum
      luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin,
      estradiol and progesterone were evaluated by the Vidas Parametric System.
      RESULTS: The LH : FSH ratio was significantly higher in the women with polycystic
      ovaries than in the ovulatory groups. IL-2 and IFN-gamma were more highly
      expressed in the follicular phase but the T-helper 2 cytokines IL-4 and IL-6
      predominated in the luteal phase, serum, peritoneal fluid and culture of the
      peritoneal mononuclear cells. From the follicular to the mid-luteal phase, IL-6
      increased three to fivefold in the serum and peritoneal fluid, but there was low
      expression with anovulation. CONCLUSIONS: The peritoneal fluid levels of IL-4 and
      IL-6 are higher in the luteal phase. Low IL-6 levels in chronic anovulation may
      be a marker of resistance to clomiphene citrate.

PMID- 12790841
TI  - Correlation between estrogen receptor alpha expression, collagen content and
      stiffness in human uterine arteries.
AB  - AIM OF THE STUDY: To investigate the relationship between estrogen receptor alpha
      expression, collagen content and distensibility of the human uterine artery.
      STUDY DESIGN: Uterine arteries (n = 13) obtained from women undergoing
      hysterectomy were mounted for length-tension relations and thereafter frozen for
      later determination of collagen and estrogen receptor alpha contents. RESULTS: A
      negative correlation between estrogen receptor alpha content and collagen content
      (r = -0.76, n = 13) and a positive correlation between collagen content and
      passive tension at 1.4 Lo (r = 0.72, n = 13) in the uterine artery were detected.
      No difference was found between pre- and postmenopausal women concerning the
      estrogen receptor alpha content, the collagen content or maximal active force.
      CONCLUSIONS: Our data show a functional correlate to the expression of estrogen
      receptors alpha, as a high content of estrogen receptor alpha correlates with a
      lower collagen concentration, indicating that estrogen through activation of
      estrogen receptor alpha protects against vascular collagen accumulation making
      the vessel more distensible.

PMID- 12790842
TI  - Serum nitric oxide metabolites and E-selectin in preterm premature rupture of
      membranes.
AB  - BACKGROUND: Diseases with low-grade inflammation perturb endothelial function. We
      investigated whether preterm premature rupture of membranes (PPROM) is associated
      with endothelial dysfunction, as assessed by the levels of endothelium-derived
      nitric oxide metabolites (NOx) and E-selectin in maternal serum. METHODS: The
      concentrations of NOx and E-selectin were measured in 32 pregnant women with
      PPROM and in 27 healthy gestational age-matched control women. The grade of
      inflammation was estimated by measuring serum C-reactive protein (CRP) and
      interleukin-6 (IL-6) concentrations. RESULTS: NOx and E-selectin concentrations
      were not different in PPROM patients as compared to controls. In 17 patients with
      PPROM, CRP rose above 12 mg/L. In this group, IL-6 concentration was
      significantly higher than among controls, but concentrations of NOx and E
      selectin remained unaltered. There was a negative correlation between the levels
      of NOx, CRP and IL-6 and the interval from PPROM to delivery. The levels of NOx
      correlated positively with those of IL-6. CONCLUSIONS: PPROM, with or without CRP
      and IL-6 surges, does not affect endothelial function markedly, as judged from
      the unaltered concentrations of NOx and E-selectin in maternal serum.

PMID- 12790843
TI  - Periconceptional use of folic acid supplements in Oslo.
AB  - BACKGROUND: Periconceptional supplementation with folic acid has been shown to
      decrease the occurrence of neural tube defects (NTD). A daily supplement of 400
      micro g folic acid from the month before pregnancy and the first 2 to 3 months of
      pregnancy is recommended in Norway. We wanted to evaluate the use of folic acid
      supplements among pregnant women in Oslo, and to explore demographic factors that
      were associated with periconceptional intake. METHODS: All women attending
      antenatal ultrasound screening at the two main obstetric departments in Oslo
      during 3 months in 2001 were invited to answer questions regarding folic acid
      supplementation before and during their present pregnancy. RESULTS: A total of
      1541 women (91, 5%) participated in the study, of which 26% were nonwestern
      immigrants. Only 17% of all women had started the folic acid supplementation
      preconceptionally (22% of the nonimmigrant vs. 2% of the immigrant population).
      Folic acid had been used by 58% at some time during the present pregnancy (73% of
      the nonimmigrant vs. 19% of the immigrant population). Regression analysis
      demonstrated that the difference in periconceptional use of folic acid between
      the two population groups could not be explained by registered demographic
      factors other than immigrant status. CONCLUSIONS: Most pregnant women in Oslo do
      not use folic acid as recommended and a dramatically low usage is seen among the
      immigrant population, indicating that more widespread information is necessary.
      Furthermore, fortification of cereals with folic acid should be considered to
      secure a sufficient intake of folic acid in all fertile women.

PMID- 12790844
TI  - Iron supplementation during pregnancy in Sweden: to what extent is the national
      recommendation followed?
AB  - BACKGROUND: While there has been a worldwide trend to reduce the recommended
      amount of iron in prenatal supplements, this has still not been implemented in
      Sweden. It is likely that the current national recommendation of 100 mg of
      iron/day to all pregnant women provides a larger amount of iron than warranted
      and results in increased occurrence of side-effects and reduced compliance. This
      may also reduce midwives' motivation to implement the recommendation. The aim of
      this study was to assess adherence to the current recommendation and to describe
      factors associated with prescription and use of iron supplements. METHODS: A
      questionnaire capturing determinants for and use of prenatal iron supplementation
      was distributed to newly delivered women and midwives in five regions of Sweden.
      In addition, an inquiry about implementation of the recommendation was sent to
      all senior obstetricians in charge of antenatal care. RESULTS: Most (79%) of the
      senior obstetricians indicated adherence to the national recommendation. A lower
      percentage of midwives (41%) and a further lower proportion of pregnant women
      (28%) did so. Despite limited compliance to the recommendation, the majority of
      pregnant women had used some type of iron-containing supplement. Side-effects of
      supplements, perceived need and advice from midwives influenced their use. Many
      midwives preferred and practiced a selective supplementation strategy.
      CONCLUSIONS: The current recommendation is not practiced. Side-effects and
      perceptions that the amount of iron is larger than necessary contribute to its
      limited use. A revision is needed to address the amount of iron required and
      strategies to ensure good adherence.

PMID- 12790845
TI  - Choice of antibiotics for infection prophylaxis in emergency cesarean sections in
      low-income countries: a cost-benefit study in Mozambique.
AB  - BACKGROUND: There is a need to assess the cost-benefit of different models of
      antibiotic administration for the prevention of post cesarean infection,
      particularly in resource-scarce settings. DESIGN: Randomized, nonblinded
      comparative study of a single combined preoperative dose of gentamicin and
      metronidazole vs. a post cesarean scheme for infection prophylaxis. METHODS:
      Pregnant women (n = 288) with indication for emergency cesarean section were
      randomly allotted to two groups. Group 1 (n = 143) received the single, combined
      dose of prophylactic antibiotics and group 2 (n = 145) received, over 7 days, the
      postoperative standard scheme of antibiotics followed in the department. Both
      groups were followed up during 7 days for detection of signs of wound infection,
      endometritis, peritonitis and urinary tract infection. MAIN OUTCOME MEASURES:
      Prevalence of postoperative infection, mean hospital stay and costs of
      antibiotics used. RESULTS: Women completing the study (n = 241) were distributed
      into group 1 (n = 116) and group 2 (n = 125). No significant difference was found
      neither in the prevalence of postoperative infection nor in the mean hospital
      stay. No death occurred. The cost of the single dose of prophylactic antibiotics
      was less than one-tenth of the cost of the standard postoperative scheme.
      CONCLUSION: In our setting, the administration of a single dose of 160 mg of
      gentamicin in combination with 500 mg of metronidazole before emergency cesarean
      section for prevention of infection is clinically equivalent to existing
      conventional week-long postoperative therapy, but at approximately one-tenth of
      the cost.

PMID- 12790846
TI  - Failed individual and sequential instrumental vaginal delivery: contributing risk
      factors and maternal-neonatal complications.
AB  - BACKGROUND: To identify the risk factors for failed instrumental vaginal
      delivery, and to compare maternal and neonatal morbidity associated with failed
      individual and sequential instruments used. DESIGN: A retrospective case-control
      study. METHODS: From January 1995 to June 2001, there were 39 508 live births at
      >37 weeks' gestation of which 2628 (6.7%) instrumental vaginal deliveries were
      performed, 1723 (4.4%) were vacuum extractions and 905 (2.3%) were forceps. A
      total of 155/2628 (5.9%) patients who had failed instrumental delivery were
      matched with 204 patients who had successful instrumental delivery. The patients
      were divided into five groups. Group I (n = 129) had failed vacuum extraction,
      group II (n = 13) failed forceps, group III (n = 13) failed both (i.e. failed
      attempt at both instruments sequentially), group IV (n = 138) had successful
      vacuum extraction and group V (n = 66) successful forceps. RESULTS: The failure
      rate for vacuum extractions 129/1723 (7.5%) was significantly higher than that
      for forceps 13/905 (1.4%) [odds ratio (OR) = 5.6, 95% CI 3-10.3]. There were no
      significant differences in all maternal complications (25.5% vs. 26.6%) between
      vacuum (groups I and IV) and forceps (groups II and V) assisted deliveries. There
      were more maternal complications in group III (46.2%) than in groups I (35.7%),
      II (23.1%) and V (27.3%) that did not reach statistical significance but were
      significantly higher than in group IV (15.9%, OR = 4.5, 95% CI 1.2-16.9). There
      was a significantly higher rate of all fetal complications in group III [11/13
      (84.6%)] than in groups I [69/129 (53.5%)], II [7/13 (53.8%)], IV [35/138
      (25.4%)] and V [22/66 (33.3%)] (OR = 4.8, 95% CI 0.9-19.9). CONCLUSIONS: Applying
      the instrument at < or =0 fetal station, nulliparous women, history of previous
      cesarean section and fetal head other than occipitoanterior position were risk
      factors for failed instrumental delivery. Sequential use of instrumental delivery
      carries a significantly higher neonatal morbidity than when a single instrument
      is used.

PMID- 12790847
TI  - Diagnostic delay in women with pain and endometriosis.
AB  - BACKGROUND: Women with endometriosis claim that delayed diagnosis is a problem.
      Anglo-American studies have shown a delay from 3 to 11 years between the onset of
      pain symptoms and the final diagnosis of endometriosis. The aim of this study was
      to find the time difference between the onset of pelvic pain symptoms and the
      final diagnosis of endometriosis among Norwegian patients. MATERIAL AND METHODS:
      Questionnaires were sent to 400 women, of whom 313 were members of the Norwegian
      Endometriosis Association and 87 were patients with endometriosis being
      hospitalized at St Olav's Hospital, Trondheim, in recent years. The response rate
      was 89%. Among the 356 questionnaires returned, 95 were excluded as not
      fulfilling the inclusion criterion of surgically verified symptomatic
      endometriosis or incomplete questionnaires. Data were analyzed from 261 women, of
      whom 223 were members of the Norwegian Endometriosis Association. In all included
      patients, pain was an indication for diagnostic surgery. RESULTS: The mean delay
      in diagnosis was 6.7 +/- 6.2 years and the median delay was 5.0 years for the two
      groups in total. There was no statistically significant difference in delay
      between the two recruitment groups. Mean delay in diagnosis had not changed
      significantly with time. Women reporting infertility in addition to pain did not
      have a significantly shorter delay. CONCLUSION: In Norway there is a considerable
      delay in the diagnosis of endometriosis, with figures comparable to results from
      Anglo-American studies. A greater awareness of symptoms of endometriosis and a
      more rapid investigation should thus be encouraged.

PMID- 12790848
TI  - Expectant management of first-trimester miscarriage in clinical practice.
AB  - BACKGROUND: The aim of this study was to evaluate treatment efficacy and patient
      compliance in women with an early miscarriage managed expectantly in routine
      clinical practice. METHODS: During 1995-98, 263 consecutive women who sought
      medical attention for an ongoing or incomplete miscarriage (gestational length
      <99 days), and who were circulatory stable and had a gestational residue
      measuring 15-50 mm (anterio-posterior, A-P diameter) on ultrasound examination
      were invited to participate in this study. Hemoglobin (Hb), C-reactive protein
      (CRP), human chorionic gonadotrophin (hCG), progesterone and Rh-factor were
      analyzed and a questionnaire regarding the pregnancy, duration of genital
      bleeding and number of days of absenteeism was completed on admission and after 1
      and 4 weeks. RESULTS: Expectant management was considered to be complete (vaginal
      ultrasound, gestational residue <15 mm after 1 week) in 83%. The patients who
      were managed successfully by expectant management had a smaller gestational
      residue (p = 0.026) and a lower mean serum progesterone level (p = 0.025) on
      referral than in the group of women with failed expectant management. A
      gynecologic infection was diagnosed in seven cases (3%) and five of the
      infections were in the group of women who underwent dilatation and curettage. No
      patient required a blood transfusion. The mean number of days of absenteeism was
      3.2 days. There were no differences in Hb levels before or after treatment,
      number of bleeding days or absenteeism between the groups. CONCLUSIONS: Expectant
      management of clinically stable patients with symptoms of early miscarriage is
      safe, efficient and well tolerated.

PMID- 12790849
TI  - Periurethral connective tissue status of postmenopausal women with genital
      prolapse with and without stress incontinence.
AB  - OBJECTIVE: Connective tissue consists mainly of collagen and structural
      glycoproteins and is considered an important factor of the supportive structures
      of the genitourinary region. Few data have been published as yet with respect to
      the role of connective tissue in pelvic floor relaxation and genuine stress
      incontinence (GSI). We compared periurethral connective tissue structures between
      continent and incontinent postmenopausal women with genital prolapse. METHODS:
      Twenty-nine women underwent pelvic floor reconstructive surgery (anterior
      colporrhaphy: n = 29, sacrospinous fixation: n = 12), with biopsies obtained from
      the periurethral region. Fifteen patients and 14 women were incontinent and
      continent, respectively. Tissue samples were investigated for localization and
      distribution of collagen (types I, III, IV, V, VI) and glycoproteins
      (fibronectin, laminin, vitronectin) using immunofluorescent microscopic
      techniques. RESULTS: Collagen types I, III, IV, V, and VI were found in all
      tissue samples. Compared with the continent women, the tissue samples of the
      incontinent women showed a significantly weaker immunohistochemical staining of
      type I, III, and VI collagen. No difference in staining patterns of collagen type
      IV and V, fibronectin, and laminin was observed between the two groups. Intact
      vitronectin was found in the periurethral tissues of all the continent women,
      whereas this glycoprotein was either absent or fragmented in the incontinent
      women. CONCLUSIONS: Our results indicate an altered metabolism of connective
      tissue in the periurethral region with a significant decrease of collagen and
      vitronectin expression in postmenopausal women with pelvic floor relaxation with
      and without GSI.

PMID- 12790850
TI  - Tension-free vaginal tape and laparoscopic mesh colposuspension in the treatment
      of stress urinary incontinence: immediate outcome and complications--a randomized
      clinical trial.
AB  - BACKGROUND: The purpose of the study was to evaluate the immediate outcome and
      complications of the tension-free vaginal tape (TVT) and laparoscopic mesh
      colposuspension (LC) procedures in the treatment of female stress urinary
      incontinence (SUI). METHODS: One hundred and twenty-eight patients suffering from
      urodynamically confirmed SUI were recruited to this multicenter, randomized
      clinical trial. After randomization there were seven drop-outs--121 patients were
      operated upon: 70 patients in the TVT group and 51 in the LC group. The patients
      were evaluated according to the study protocol before operation and 6 weeks after
      it. The independent sample t-test and the Mann-Whitney U-test were used to
      calculate statistical differences between the study groups. RESULTS: Immediate
      cure rates, defined as negative stress test with 300 mL saline in the bladder,
      were similar (92.9% in the TVT group and 88.2% in the LC group; p = ns). Return
      to normal voiding was faster in the TVT group (9.2 h in the TVT group vs. 24.4 h
      in the LC group; p = 0.004). Fewer analgesics were used in the TVT group and
      hospital stay was shorter in this group. Complication rates associated with the
      procedures were similar and the number of complications was small. CONCLUSIONS:
      The immediate outcome of both procedures is the same. The rates of complications
      were similar. However, the TVT procedure seems to be less invasive and requires
      fewer hospital resources than LC.

PMID- 12790851
TI  - Paraneoplastic cerebellar degeneration with ovarian endometroid carcinoma.

PMID- 12790852
TI  - Vaginal mesh erosion 7 years after a sacral colpopexy.

PMID- 12790853
TI  - The nineteenth pregnancy in a patient with cor pulmonale and severe pulmonary
      hypertension: a management challenge.

PMID- 12790854
TI  - Severe syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) in
      the 18th week of pregnancy associated with the antiphospholipid-antibody
      syndrome.

PMID- 12790855
TI  - Advanced maternal age parturient: is there reason for concern?

PMID- 12790857
TI  - Irish nursing comes of age.

PMID- 12790856
TI  - Hormone replacement therapy and risk of breast cancer: the role of progestins.
AB  - Epidemiological studies have shown an increased risk of breast cancer associated
      with the use of hormone replacement therapy (HRT). This notion is mostly based on
      studies from the USA. During the last decades unopposed estrogen treatment has
      been used to a lesser extent, whereas the combined estrogen-progestin treatment
      regime is now prescribed worldwide. In the USA the predominant compounds are
      conjugated estrogens and medroxyprogesterone-acetate, whereas oestradiol combined
      with testosterone-like progestins is commonly used in Europe. These differences
      are largely the result of traditions. Recent studies originating from both the
      USA and Europe suggest that the combined treatment regimens with estrogen and
      progestin increase the risk of breast cancer beyond the risk following the use of
      unopposed estrogen. At present it is not known if progestins with different
      androgenicity influence the risk of breast cancer to a varying degree. This
      review focuses on studies published after the latest meta-analysis in 1997, with
      special attention given to the type of progestin used and the treatment mode,
      i.e., cyclical or continuous regimen.

PMID- 12790859
TI  - Thai nurses' beliefs about breastfeeding and postpartum practices.
AB  - Cultural beliefs are important determinants of health care behaviours. Nurses
      have an important influence on infant feeding decisions and maternal postpartum
      care, but little is known about the extent to which their practice is influenced
      by traditional beliefs and/or recent innovations driven by evidence-based
      research. The aim of this study was to investigate Thai nurses' traditional
      beliefs about breastfeeding and related postpartum care, and their impact on
      nursing practice. A survey of 372 nurses working in hospitals and health services
      in Ubon Ratchathani, Thailand was undertaken. Questionnaire items were developed
      from a review of the literature and exploratory interviews with Thai women.
      Descriptive statistics were used to represent the incidence of particular beliefs
      and behaviours. Chi-square analyses were conducted to determine relationships
      between demographic characteristics and traditional beliefs and practices. There
      were discrepancies between nurses' beliefs and contemporary evidence-based
      practices. Many nurses supported traditional Thai postpartum practices such as
      food restrictions and encouraging hot baths. Some traditional beliefs supported
      by nurses may be detrimental to women and babies such as "lying by fire",
      discarding of colostrum, and giving boiled water to neonates. Only half the
      nurses reported that they encouraged mothers to breastfeed immediately following
      birth. The study was undertaken in the North-East of Thailand, where the
      population is known to have strong belief systems. Reliability and content
      validity of the tool would be enhanced through replication studies and
      qualitative investigations of other breastfeeding issues. There is a need for
      professional development strategies such as peer review and mentoring to address
      inadequate knowledge and outdated practices of some health professionals, as well
      as continuity of care models to assess quality care outcomes that are culturally
      appropriate.

PMID- 12790858
TI  - Agency nursing work in acute care settings: perceptions of hospital nursing
      managers and agency nurse providers.
AB  - There is a paucity of research in investigating agency nursing work from the
      perspectives of hospital nursing managers and agency nurse providers. This
      exploratory paper examines the hospital nursing managers' and agency nurse
      providers' perceptions and experiences of agency nursing work. Individual, in
      depth interviews were conducted with three agency nurse providers and eight
      hospital nursing managers. Because of the lack of previous research in this area,
      an exploratory, semi-structured interviewing technique was deemed appropriate.
      Three major themes emerged from interview data: planning for ward allocation,
      communication and professionalism. In planning for ward allocation, hospital
      managers were primarily concerned with maintaining adequate numbers of nursing
      staff in the ward settings. A major concern for agency nurse providers was
      inappropriate allocation of temporary staff. Communication was valued in
      different ways. While hospital managers focused on communication between the
      agency nurse and other permanent members of the health care team, agency
      providers were concerned with exchanges between agencies and hospital
      organizations, and between the agencies and agency nurses. For both groups,
      responsibility for professional development and the status of agency nursing as a
      career choice for graduate and experienced nurses were the focal aspects for
      consideration. A limitation of this study is the small number of individual
      interviews conducted with hospital nursing managers and agency nurse providers.
      Nevertheless, the findings represent the views of 11 individuals in senior
      managerial roles. The findings reinforce the need to enhance collaboration
      between hospitals and nursing agencies, and to examine how divergent views of
      agency nursing work could be reconciled--with the aim of providing quality
      patient care.

PMID- 12790860
TI  - Critical care nurses' use of decision-making strategies.
AB  - Effective decision-making has the potential to facilitate improvements in health
      care. This paper reports several aspects of a study which used "thinking aloud"
      within a concept attainment framework to examine the decision-making processes of
      expert critical care nurses in relation to haemodynamic monitoring. The purpose
      of this study was to examine whether hypotheses were used in the decision-making
      process and, if so, were hypotheses deactivated when no longer relevant. In
      addition, the strategies that were used during the decision-making process were
      examined. Eight expert critical care nurses consented to participate in the study
      after ethics clearance was obtained from both the University and Hospital ethics
      committees. The majority of expert critical care nurse participants in this study
      demonstrated extensive use of hypotheses to explain the relationship between
      attributes and concepts. There was no evidence of specific deactivation of
      hypotheses when they were no longer relevant. Participants demonstrated use of a
      range of decision-making strategies, with a Focus Gambling Strategy being the
      most common. The reason for using different decision-making strategies was not
      clear and may represent variation between decision-makers or between scenarios
      for each individual decision-maker. Recommendations are made to help improve
      critical care nurses' decision-making.

PMID- 12790861
TI  - A prospective, randomized study of ventilator-associated pneumonia in patients
      using a closed vs. open suction system.
AB  - The objective of this study was to verify the incidence of nosocomial pneumonia
      in intubated and extended mechanically ventilated patients having endotracheal
      suctioning by an open vs. closed suction method aiming to decrease nosocomial
      pneumonia. Twenty-four (51.1%) patients received open-tracheal suction and 23
      (48.9%) received closed-tracheal suction. The inclusion criteria were: surgical
      and medical patients older than 13 years, undergoing mechanical ventilation for
      more than 48 hours. Additional data were gathered using the Acute Physiology and
      Chronic Health Evaluation II, and details on smoking, alcoholism, diabetes
      mellitus, renal failure, previous lung disease, and previous use of antibiotics,
      steroids, H2 antagonists and antacids. Among the 24 patients having open-tracheal
      suction, 11 developed nosocomial pneumonia while of the 23 patients undergoing
      closed-tracheal suction, seven developed infection (P = 0.278). Risk factors for
      nosocomial pneumonia were not significantly different between the two groups. In
      the final logistical regression model the following variables remained: groups
      (open and closed) [odds ratio (OR) = 0.014; confidence interval (CI) = 0.001
      0.416; P = 0.014] and use of prior antibiotics (OR = 2.297; CI = 1.244-4.242; P =
      0.008). Use of a closed suction system did not decrease the incidence of
      nosocomial pneumonia when compared with the open system. The exogenous risk
      factors were the most important for acquiring this infection.

PMID- 12790862
TI  - Immediate needs of adult family members of adult intensive care patients in Hong
      Kong.
AB  - Having a family member admitted to Intensive Care Unit (ICU) is stressful for the
      whole family. Stress can hinder family members' coping and thus affect the
      support that is given to patient. In order to lessen the effect of stress, family
      members' immediate needs must be identified and met. The aim of this study was to
      explore the immediate needs of adult family members of adult intensive care
      patients in Hong Kong. The study adopted a descriptive cross-sectional design.
      The Chinese version of Critical Care Family Need Inventory (CCFNI) was used to
      investigate the immediate needs of a convenience sample of 40 adult family
      members of patients in an adult ICU. Data were collected through personal
      interviews within 24-72 hours of patients' admission. Findings revealed that 25
      out of 45 need items on the CCFNI that were rated as important or very important.
      The need "to know the expected outcome" was ranked as the most important. All the
      needs related to reassurance were ranked within the top 10 important needs. The
      top 10 important needs were met by doctors and nurses. There were significant
      differences in needs between family members with different gender, experience of
      visiting ICUs, religious background and characteristics of patients. The findings
      suggest that family members perceived reassurance and information support as
      important. Although this study was limited by using a small convenience sample,
      the findings could still provide insight for nurses working in ICUs.

PMID- 12790863
TI  - Power imbalance between nurses and patients: a potential inhibitor of partnership
      in care.
AB  - The Patient's Charter identifies the need for nurses to respect patients' rights
      to influence their care, and contemporary nursing practice advocates that nurses
      work in partnership with patients. Hence nurses are encouraged to share their
      power and facilitate empowerment in their patients by giving them information and
      support. However, the literature indicates that nurses are not very successful in
      making patients feel empowered to make informed decisions. This study, conducted
      in 1998, provides some answers as to why this may be the case. The aim of the
      study was to explore and describe nurses' and patients' views regarding
      partnership in care in hospital. Using the grounded theory approach, participants
      were drawn from four hospitals in Western Australia. A purposive sample of 33
      nurses and 32 patients were interviewed in-depth. Participant observation was
      also conducted and field notes were written. The interviews were transcribed
      verbatim and analysed using the constant comparative method. The findings showed
      that nurses viewed involving patients in care as requiring them to give patients
      information and to share their decision-making powers with them. With the
      exception of a few, the majority of nurses were unwilling to share their decision
      making powers. This created a situation of power imbalance with subsequent little
      patient input. Factors identified included nurses' beliefs that they "know best",
      the view that patients lacked medical knowledge and the perceived need for nurses
      to hold onto their power and maintain control. If nurses and patients are to work
      as partners, it is important that nurses make every effort to equalize the power
      imbalance. One way to do this is for nurses to share and give information to
      patients readily and to be open in their communication with them.

PMID- 12790864
TI  - Demand for nursing competencies: an exploratory study in Taiwan's hospital
      system.
AB  - Along with increasing complexity of nursing services, hospital employers are
      demanding qualified and competent staff nurses for high quality clinical care. In
      Taiwan, disparities in the demand for competent nurses by employers and the
      supply produced by nursing educators still exist and require attention. A
      comprehensive understanding of the specific needs of Taiwan's medical care system
      for nursing services would help bridge the current gap between demand for and
      supply of competently trained nurses. This exploratory study investigated
      hospital employers' perceptions of the extent to which the nursing skills
      identified by Cleary et al. [Image: Journal of Nursing Scholarship (1998)20(4):39
      42] were needed for staff nurses in Taiwan's medical care system. There were a
      total of 21 nursing competencies and classification on these items was also
      implemented. A cross-sectional, quantitative, survey design was conducted.
      Subjects' participation was voluntary, an information leaflet and an informed
      consent form was included in the questionnaire. A total of 89 nursing employers
      (nursing directors, associate directors, supervisor, or head nurse) participated,
      resulting in a 42.6% response rate. Factor analysis grouped these skills into
      three factors: basic-level patient care, intermediate-level patient care and
      basic management, and advanced-level patient care and supervision. This study
      confirmed that levels of nursing competencies needed differed by type of hospital
      accreditation. These levels also varied depending on types of services provided,
      employers' professional titles and tenure of currently employed nurses. The
      questionnaire developed for this study could be used as one of the tools to
      communicate demand and supply of nursing competencies between nurse educators and
      employers. These competencies could be used to develop a checklist for evaluating
      adequacy of nursing programmes in order to meet nurses' new roles and
      responsibilities and improve nursing care quality in the fast-changing health
      care environment in Taiwan.

PMID- 12790865
TI  - Medication calculation skills of nurses in Finland.
AB  - The aim of this study was to describe the medication calculation skills of nurses
      in Finland. We tried to ascertain how nurses evaluate their own medication
      calculation skills and how these self-evaluations are associated with various
      background factors and the actual level they score in a calculation test. In the
      spring of 2000, nurses (n = 546) in one Finnish university hospital completed a
      questionnaire specially developed for this study. The instrument included
      structured questions, statements and a medication calculation test. The response
      rate was 56%. Data analysis was based on descriptive statistics. The nurses found
      the mathematics and dosage calculation easy and interesting but the pharmacology
      difficult. They evaluated their own mathematical and dosage calculation skills as
      sufficient, although it had certain shortcomings. The youngest nurses (20-29
      years) evaluated their mathematical and dosage calculation skills as sufficient
      and they also succeeded in the calculation test. Basic (High School) education
      was associated with better calculation skills. The findings of this study support
      the need and importance of checking and maintaining one's medication calculation
      skills.

PMID- 12790866
TI  - International clinical placements for undergraduate students.
AB  - This paper reports the findings of a study that sought to gain insight into the
      experiences of third year nursing students who participated in a 4-week clinical
      placement in an international setting. This study is different from many studies
      describing international placements for undergraduate nursing students as it
      concentrates on clinical experiences on placement. Students' reflective journals
      and face-to-face discussions were used to collect data, which were analysed by
      thematic content analysis. Categories were identified describing a focus on micro
      clinical-based issues that expanded over time to a focus on broader issues
      reflecting the "nursing culture" of the placement. Students described both
      positive and negative aspects of being placed in an international clinical
      setting, with the concept of "being different" emerging. Whilst the findings
      cannot be generalized beyond the sample, the study highlights the importance of
      adequate preparation and support for students on international clinical
      placements, with emphasis on attention to clinical detail.

PMID- 12790867
TI  - Nurses' attitudes towards perinatal bereavement support in Hong Kong: a pilot
      study.
AB  - The purpose of this study is to explore nurses' attitudes towards perinatal
      bereavement care and to identify required support and training needs for nurses
      on bereavement care in Hong Kong. Data were collected through a structured
      questionnaire, and 110 nurses were recruited from the obstetrics and gynaecology
      unit in one of the largest public hospitals in Hong Kong. The majority of nurses
      held a positive attitude towards bereavement care. A significant difference in
      nurses' attitudes towards bereavement support was found in terms of demographics,
      practical experiences and training factors. The results showed that only 25.5% (n
      = 28) of nurses had bereavement-related training. In contrast, 90.9% of nurses
      showed a positive response to grief training and 90.0% would share experiences
      with colleagues and seek support when feeling under stress. The findings also
      suggest that nurses' attitudes towards bereavement care are positively correlated
      with bereavement care training needs (r = 0.53) and hospital policy support (r =
      0.55). Hong Kong nurses' attitudes towards perinatal care emphasized their need
      for increased knowledge and experience, improved communication skills, and
      greater support from team members and the hospital. These findings may be used
      for Hong Kong health care professionals to improve support of nurses, to ensure
      delivery of sensitive bereavement care in perinatal settings and to enhance
      nursing school curricula.

PMID- 12790868
TI  - "It's like an explosion in your life...": lay perspectives on stress and
      myocardial infarction.
AB  - Psychological difficulties are common after myocardial infarction (MI). These
      difficulties are most often represented to patients through cardiac
      rehabilitation services and the literature offered to patients after MI as being
      related to "stress" and its management. However, no research has examined what MI
      patients understand by the term "stress" or how congruent lay views of stress are
      with those evident in the professional literature. The aim of the study reported
      here was to examine post-MI patients' views of stress, its functioning and
      relationship to their MI. As patients' views of stress were sought, qualitative
      interviews were used. A philosophical approach was taken (critical realism) that
      recognizes the legitimacy of both professional and lay perspectives. Data were
      generated in 44 semistructured interviews with 14 MI patients who were
      interviewed 48 hours, 1 week, 1 month and 3 months after hospital admission.
      While participants described their experiences after MI as being difficult, to
      convey this they used everyday terms such as fear, fright and worry. Rather than
      viewing stress as being a consequence of their MI, they perceived it to be a
      common cause of heart problems. Many considered stress as having a more
      influential role than other risk factors, such as smoking and diet. They
      expressed a wide variety of sophisticated and diverse views of stress and its
      functioning. Each of these views placed different weighting on the roles of
      social, personal and situational factors in contributing to the stressful
      reaction. Parallels were apparent between these lay accounts and theories of
      stress developed in the professional literature.

PMID- 12790869
TI  - Indices for studying urinary incontinence and levator ani function in primiparous
      women.
AB  - Urinary incontinence (UI) is a complex phenomenon that is prevalent in pregnant
      and parous women and requires the use of sophisticated measures to adequately
      reflect functioning of the continence system. The purpose of this study was to
      develop reliable and valid measures of UI and levator ani function for use in
      research and clinical settings. A Leakage Index (LI) and a Levator Ani Function
      Index (LAFI) were developed using data from a longitudinal study of primiparous
      women. Reliability and validity tests were conducted to: (i) estimate the
      internal consistency reliability of each index, (ii) determine whether the
      indices captured change in continence status and pelvic floor function during
      pregnancy through 1 year postpartum, and (iii) estimate association between the
      indices as a test of predictive validity. Cronbach's alpha ranged from 0.72 to
      0.84 for the LI and from 0.53 to 0.79 for the LAFI across the six data collection
      time points of the study. Average LI scores increased late in pregnancy and
      decreased postpartum, though not significantly. Average LAFI scores decreased
      significantly at 35 weeks gestation (t = 4.84, P = 0.000) and increased
      significantly at 12 months postpartum (t = -3.51, P = 0.002) relative to
      baseline. The LI and LAFI were significantly associated at 20 weeks gestation
      (Pearson r = -0.40, P = 0.007) and at 6 weeks postpartum (Pearson r = -0.33, P =
      0.029). The findings suggest the LI and LAFI are reliable and valid measures of
      UI and levator ani function in primiparous women, which can be used with
      confidence in clinical and research settings.

PMID- 12790870
TI  - Lived experiences of eating problems for patients with head and neck cancer
      during radiotherapy.
AB  - Only a small proportion of cancer patients undergo radical radiotherapy to the
      head and neck, but their needs are particularly complex. Although extensive
      research describes the side-effects of radiotherapy to the head and neck, few
      studies focus on patients' subjective experiences of eating problems and the
      impact these have on the patients' daily life. In this study a phenomenological
      approach was used, as the purpose was to acquire deeper understanding of head and
      neck cancer patients' lived experiences of eating problems, their consequences in
      daily life and patients' strategies of coping with these problems. Eight patients
      from two radiation therapy departments in mid-Sweden were interviewed in an open
      dialogue. Data analysis was based on Colaizzi's method. Eating problems
      experienced were captured in two interrelated main themes: "Ability to chew and
      swallow" and "Will and desire to eat". The eating problems were found to cause a
      number of severe consequences in daily life. These are incorporated into one main
      theme: "The way of life is disturbed". Ways to cope with this disturbance were
      captured in one main theme: "Trying to see the end - To survive". This study
      identifies the need to view eating problems as a complex phenomenon in a specific
      context including the individual patient's life situation. The findings create
      the opportunity to develop nursing interventions based on patients' own needs. To
      facilitate this, a specialist nurse should be responsible for reviewing patients
      regularly throughout radiation therapy. Intervention studies are needed to
      provide optimal clinical guidelines.

PMID- 12790871
TI  - The experience of sexuality for individuals living with multiple sclerosis.
AB  - Little is known of the experience of sexuality among people living with multiple
      sclerosis (MS). This Roy Adaptation Model-based study focused on identifying the
      experiences of sexuality reported by individuals living with MS. A qualitative,
      naturalistic case study method was employed. Five women and three men diagnosed
      with MS were interviewed by telephone three times over a period of 1 year. The
      telephone interview guide consisted of a series of structured questions. Analysis
      of the telephone interview transcripts revealed three themes. The theme, "How I
      Feel About My Appearance", reflected elements of the Roy model physiological,
      self-concept, role function and interdependence modes. The theme, "I Have
      Feelings About My Sexuality", reflected the self-concept and interdependence
      modes, and the theme, "Sexuality For Me Has Both Negative and Positive Emotions",
      reflected the self-concept and interdependence modes. The small sample size
      precludes generalization of the results to all individuals living with MS. Nurses
      and other health care providers need to recognize that sexuality is an important
      issue for individuals with MS. Researchers should continue to examine experiences
      of sexuality in a larger sample of individuals with MS and also should begin to
      examine the effects of nursing interventions, such as support groups and
      individual counselling, on feelings about sexuality in individuals with MS.

PMID- 12790872
TI  - Postoperative cognitive changes among older Taiwanese patients.
AB  - The purpose of the study was to describe variations in cognitive/behavioural
      changes during the course of delirium among older Taiwanese patients after
      elective surgery. A total of 106 patients assessed four times (admission, onset
      of delirium, delirium day 3 and delirium day 5) by the Mini Mental State
      Examination (MMSE) were included in the analysis to understand the
      neurocognitive/behaviour change during the course of delirium. Repeated measures
      anova was used to analyse within-subject differences across these four time
      points for those who became delirious and those who did not. The findings showed
      that patients who experienced delirium had significantly (P < 0.01) lower MMSE
      scores than non-delirious patients. Scores for the delirious group were also
      significantly different across the four assessments (P < 0.01) within the group.
      The subscales of orientation to time, orientation to place, registration and
      recall were the major changes from time 1 (admission assessment) to time 2 (onset
      of delirium) for delirious patients. When scores for time 4 (delirium day 5) and
      time 1 (admission assessment) were compared, the subscales of orientation to
      time, orientation to place and visual construction showed the least improvement
      among the subscales at time 4. The findings of the study suggest that mental
      status assessments are important during the patient's admission and hospital
      stay. The repeated assessments can be incorporated into routine nursing care so
      that problems can be detected and appropriate nursing care implemented.

PMID- 12790873
TI  - Finnish nurses' views on their research activities.
AB  - The purpose of the study reported here was to describe Finnish nurses' research
      and publication activities, as well as their views on the availability and
      utilization of research results in nursing practice. The data were collected
      using a structured questionnaire in which obstacles to the utilization of
      research results were measured with a previously developed instrument. A total of
      400 nurses from community health centres, a central hospital and a central
      university hospital took part. Most of the nurses had carried out research on
      their own. Age, experience, training in research and development and other
      further training, as well as reading the nursing literature, were associated with
      doing research. Some of the reasons why the nurses had not carried out research
      were revealed. Publication of results was very rare. There were problems with the
      availability of research results. The most common obstacles to research
      utilization had to do with the presentation of results and the setting. In
      research utilization, respondents received most support from the ward manager and
      least support from doctors. If we want to encourage nurses to do research and
      increase the utilization of research results, greater effort should be invested
      in teaching research methodology, in introducing more flexible working hours and
      in developing other support systems.

PMID- 12790874
TI  - Meanings of giving touch in the care of older patients: becoming a valuable
      person and professional.
AB  - Touch is central to nursing and health care workers frequently touch their
      patients, consciously or unconsciously in their interactions with them. Most
      literature has studied touch from a patient perspective, thus inquiry about
      professionals' experiences are rare. The aim of this study was to illuminate
      meanings of giving touch in nursing care of older patients. To understand the
      meaning of lived experiences of giving touch in care of older patients,
      interviews with 12 health care professionals in northern Sweden were analysed
      using a phenomenological-hermeneutic approach influenced by the philosophy of
      Ricoeur. The findings show that giving touch in the care of older patients is a
      transforming experience, where one suddenly perceives oneself as both a valuable
      person and professional who no longer powerlessly confronts patients' haunted and
      disrupted bodies, but who, by means of touch, has gained power to ease this
      suffering. The experience also transforms the way one regards older patients.
      Instead of seeing a severely demanding patient suffering from dementia and/or
      pain, one is able to see the person behind the disease as a human being, like
      oneself. A relationship described as calm, friendly and humane is created between
      caregiver and patient when giving touch, a relationship that transcends the
      moment of touch and influences one's way of caring. This understanding is
      presented using the theoretical framework of the philosophy of Marcel. Giving
      touch has the power to shed new light on health care professionals' experiences
      of caring for older patients suffering from dementia and/or pain, giving them the
      power to be a valuable person and professional.

PMID- 12790875
TI  - How to manage and display qualitative data using "Framework" and Microsoft Excel.

PMID- 12790881
TI  - Epidemiology of neural tube defects.
AB  - Neural tube defects (NTDs)-malformations secondary to abnormal neural tube
      closure between the third and fourth weeks of gestational age-have a complex and
      imperfectly understood etiology in which both genetic and environmental factors
      appear to be involved. A number of specific chromosomal or single-gene disorders,
      presumably not affected by environmental influences, are associated with the
      development of NTDs, but such syndromal cases account for a small proportion of
      NTDs in live-born infants. Analysis of recurrence patterns within families and of
      twin-concordance data provides evidence of a genetic influence in nonsyndromal
      cases, but factors such as socioeconomic status and geographic area (independent
      of race or ethnicity) are also associated with variations in the incidence of
      NTDs. The prevalence at birth of both anencephaly and spina bifida has decreased,
      but the advent of antenatal diagnosis and elective termination of affected
      pregnancies has undermined the reliability of birth prevalence rate as an
      estimate of incidence. Some occupational and other exposures, including maternal
      use of antiepileptic drugs (AEDs), are associated with increased risk for NTDs.
      Among women who have had an NTD-affected pregnancy, recurrence risk is markedly
      higher than the risk for a first NTD-affected pregnancy in the general
      population. There is strong evidence, overall, for a protective effect of
      adequate folate consumption. In some high-risk groups, however, such as women
      taking AEDs, folate supplementation has not been proven to reduce NTD risk.

PMID- 12790883
TI  - Pharmacology of neural tube defects.
AB  - The pharmacology of neural tube defects (NTDs) is a complex issue. Several
      theories regarding the etiology of NTDs emphasize the importance of interactions
      between genetic, environmental, and biochemical factors at a key point in time.
      One such factor is chronic drug therapy, a potential consequence of which is the
      formation of toxic drug metabolites, including free radicals (FRs), which have
      been implicated in the etiology of NTDs. Under normal physiological conditions,
      FRs are quickly destroyed by antioxidant defense systems. However, FR-mediated
      cellular damage can occur if these defense systems fail or are overburdened, such
      as in patients who are genetically deficient in FR scavenging enzyme activity
      (FRSEA) or who are receiving chronic drug therapy. Congenital defects, including
      NTDs, resulting from FR-induced damage have been reported in both experimental
      animals and humans. For example, the use of antiepileptic drugs (AEDs) during
      pregnancy that have the propensity to form FRs during their metabolism are
      associated with an increased risk of the development of congenital malformations,
      including NTDs. This article reviews the biochemistry of FRs, the factors
      regulating FR scavenging capacity, and the theories regarding the etiology of
      NTDs; presents a hypothesis of a unified mechanism for AED-induced NTDs and other
      congenital defects; and briefly discusses the roles of folate and selenium in the
      prevention of NTDs.

PMID- 12790882
TI  - Pathobiology and genetics of neural tube defects.
AB  - PURPOSE: Neural tube defects (NTDs), including spina bifida and anencephaly, are
      common congenital malformations that occur when the neural tube fails to achieve
      proper closure during early embryogenesis. Based on epidemiological and clinical
      data obtained over the last few decades, it is apparent that these multifactorial
      defects have a significant genetic component to their etiology that interacts
      with specific environmental risk factors. The purpose of this review article is
      to synthesize the existing literature on the genetic factors contributing to NTD
      risk. RESULTS: To date, there is evidence that closure of the mammalian neural
      tube initiates and fuses intermittently at four discrete locations. Disruption of
      this process at any of these four sites may lead to an NTD, possibly arising
      through closure site-specific genetic mechanisms. Candidate genes involved in
      neural tube closure include genes of the folate metabolic pathway, as well as
      those involved in folate transport. CONCLUSIONS: Although extensive efforts have
      focused on elucidating the genetic risk factors contributing to the etiology of
      NTDs, the population burden for these malformations remains unknown. One group at
      high risk for having children with NTDs is epileptic women receiving
      antiepileptic medications during pregnancy. Efforts to better understand the
      genetic factors that may contribute to their heightened risk, as well as the
      pathogenesis of neural tube closure defects, are reviewed herein.

PMID- 12790884
TI  - Clinical care of pregnant women with epilepsy: neural tube defects and folic acid
      supplementation.
AB  - Women with epilepsy (WWE) have a risk of bearing children with congenital
      malformations that is approximately twice that of the general population. Most
      antiepileptic drugs (AEDs) have been associated with such risk. Valproate and
      carbamazepine have been associated specifically with the development of neural
      tube defects (NTDs), especially spina bifida. Other factors may contribute to the
      risk, including concomitant diseases such as diabetes mellitus, occupational
      exposure to teratogens, excessive prepregnancy weight, and various nutrient
      deficiencies. In the general population, maternal folate deficiency, in
      particular, has been linked with the development of NTDs, and periconceptional
      folate supplementation with a reduction of risk. It is unclear whether folate
      supplementation has a comparable protective effect for WWE. Data concerning the
      risk for congenital malformations associated with the newer AEDs (gabapentin,
      felbamate, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and
      zonisamide) are still limited. Several pregnancy registries for women taking AEDs
      have been established. Comprehensive postmarketing surveillance, regionally or
      nationally, might be the ideal method of monitoring medication safety, but
      government support for such an undertaking has for the most part been lacking.
      Despite uncertainty about the efficacy of periconceptional folate supplementation
      in WWE, these women should receive such supplementation at dosage levels
      recommended for the general population of women of childbearing age. Seizure
      control must not be neglected in a pregnant woman with epilepsy since seizures
      are associated with harm to the fetus as well as the mother. Risk may be
      minimized by using a single AED at the lowest effective dosage.

PMID- 12790885
TI  - Case reports of women with epilepsy.

PMID- 12790886
TI  - Practice parameter: temporal lobe and localized neocortical resections for
      epilepsy.
AB  - PURPOSE: To examine evidence for effectiveness of anteromesial temporal lobe and
      localized neocortical resections for disabling complex partial seizures. METHODS:
      Systemic review and analysis of the literature since 1990. RESULTS: One intention
      to-treat Class I randomized controlled trial of surgery for mesial temporal lobe
      epilepsy found that 58% of patients randomized to be evaluated for surgical
      therapy (64% of those who received surgery) were free of disabling seizures and
      10 to 15% were unimproved at the end of 1 year, compared with 8% free of
      disabling seizures in the group randomized to continued medical therapy. There
      was a significant improvement in quantitative quality-of-life scores and a trend
      toward better social function at the end of 1 year for patients in the surgical
      group, no surgical mortality, and infrequent morbidity. Twenty-four Class IV
      series of temporal lobe resections yielded essentially identical results. There
      are similar Class IV results for localized neocortical resections; no Class I or
      II studies are available. CONCLUSIONS: A single Class I study and 24 Class IV
      studies indicate that the benefits of anteromesial temporal lobe resection for
      disabling complex partial seizures is greater than continued treatment with
      antiepileptic drugs, and the risks are at least comparable. For patients who are
      compromised by such seizures, referral to an epilepsy surgery center should be
      strongly considered. Further studies are needed to determine if neocortical
      seizures benefit from surgery, and whether early surgical intervention should be
      the treatment of choice for certain surgically remediable epileptic syndromes.

PMID- 12790887
TI  - Calorie restriction and ketogenic diet diminish neuronal excitability in rat
      dentate gyrus in vivo.
AB  - PURPOSE: The ketogenic diet (KD) is an effective treatment for intractable
      epilepsy. However, little is known about its underlying mechanisms. METHODS: In
      this study, in vivo extracellular field responses to angular bundle stimulation
      were recorded in the dentate gyrus of Sprague-Dawley rats fed one of three diets:
      ketogenic calorie-restricted (KCR), normal calorie-restricted (NCR), or normal ad
      libitum (NAL). Input/output curves and paired-pulse relations were used to assess
      network excitability. A maximal dentate activation (MDA) protocol was used to
      measure electrographic seizure threshold and duration. RESULTS: Animals fed
      calorie-restricted (CR) diets exhibited greater paired-pulse inhibition, an
      elevated MDA threshold, and an absence of spreading depression-like events
      compared with ad libitum-fed controls. In the MDA model of epileptogenesis, the
      rate of increase in electrographic seizure duration after repeated stimuli was
      markedly reduced in KCR-fed animals compared with NCR- and NAL-fed controls.
      CONCLUSIONS: These data suggest that CR, by itself, can be anticonvulsant, and
      treatment with a KCR diet may be both anticonvulsant and antiepileptogenic.

PMID- 12790888
TI  - Intrastriatal methylmalonic acid administration induces convulsions and TBARS
      production, and alters Na+,K+-ATPase activity in the rat striatum and cerebral
      cortex.
AB  - PURPOSE: Methylmalonic acid (MMA) inhibits succinate dehydrogenase (SDH) and beta
      hydroxybutyrate dehydrogenase activity in vitro. Acute intrastriatal
      administration of MMA induces convulsions through glutamatergic mechanisms
      probably involving primary adenosine triphosphate (ATP) depletion and free
      radical generation. In this study we investigated whether the intrastriatal
      administration of MMA causes lipoperoxidation and alteration in Na+, K+-ATPase
      activity ex vivo and characterized the electrographic changes elicited by the
      intrastriatal administration of this organic acid. METHODS: MMA-induced
      lipoperoxidation, alterations in Na+, K+-ATPase activity and electrographic
      changes were measured by measuring total thiobarbituric acid-reacting substances
      and inorganic phosphate release by spectrophotometry, and by depth electrode
      recording, respectively. RESULTS: We demonstrated that intrastriatal MMA (6 mmol)
      injection causes convulsive behavior and electrographically recorded convulsions
      that last approximately 2 h. Concomitant with the increase of thiobarbituric acid
      reacting substances (TBARS) content, we observed a significant inhibition of
      Na+,K+-ATPase activity in the striatum, and activation of Na+,K+-ATPase activity
      in the ipsilateral cerebral cortex. Intrastriatal MMA injection increased the
      content of TBARS in the striatum measured 30 min (32.4 +/- 12.0%, compared with
      the noninjected contralateral striatum) and 3 h (39.7 +/- 5.1%, compared with the
      noninjected contralateral striatum) after MMA injection. TBARS content of the
      ipsilateral cerebral cortex increased after MMA injection at 30 min (42.1 +/-
      6.0%) and 3 h (40.4 +/- 20.2%), and Na+,K+-ATPase activity in the ipsilateral
      cerebral cortex increased during ictal activity (113.8 +/- 18%) and returned to
      basal levels as electrographic convulsions vanished in the cortex. Interestingly,
      intrastriatal MMA administration induced a persistent decrease in Na+,K+-ATPase
      activity only in the injected striatum (44.9 +/- 8.1% at 30 min and 68.7 +/- 9.4
      at 3 h). CONCLUSIONS: These data suggest that MMA induces lipoperoxidation
      associated with Na+,K+-ATPase inhibition or activation, depending on the cerebral
      structure analyzed. It is suggested that Na+,K+-ATPase inhibition may play a
      primary role in generating MMA-induced convulsions.

PMID- 12790889
TI  - In vivo modulation of hippocampal epileptiform activity with radial electric
      fields.
AB  - PURPOSE: Electric field stimulation can interact with brain activity in a
      subthreshold manner. Electric fields have been previously adaptively applied to
      control seizures in vitro. We report the first results from establishing suitable
      electrode geometries and trajectories, as well as stimulation and recording
      electronics, to apply this technology in vivo. METHODS: Electric field
      stimulation was performed in a rat kainic acid injection seizure model. Radial
      electric fields were generated unilaterally in hippocampus from an axial depth
      electrode. Both sinusoidal and multiphasic stimuli were applied. Hippocampal
      activity was recorded bilaterally from tungsten microelectrode pairs. Histologic
      examination was performed to establish electrode trajectory and characterize
      lesioning. RESULTS: Electric field modulation of epileptiform neural activity in
      phase with the stimulus was observed in five of six sinusoidal and six of six
      multiphasic waveform experiments. Both excitatory and suppressive modulation were
      observed in the two experiments with stimulation electrodes most centrally placed
      within the hippocampus. Distinctive modulation was observed in the period
      preceding seizure-onset detection in two of six experiments. Short-term
      histologic tissue damage was observed in one of six experiments associated with
      high unbalanced charge delivery. CONCLUSIONS: We demonstrated in vivo electric
      field modulation of epileptiform hippocampal activity, suggesting that electric
      field control of in vivo seizures may be technically feasible. The response to
      stimulation before seizure could be useful for triggering control systems, and
      may be a novel approach to define a preseizure state.

PMID- 12790890
TI  - Is the cell death in mesial temporal sclerosis apoptotic?
AB  - PURPOSE: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the
      hippocampus. Studies on experimental models and patients with intractable
      epilepsy suggest that apoptosis may be involved in neuronal death induced by
      recurrent seizures. METHODS: We searched evidence for apoptotic cell death in
      temporal lobes resected from drug-resistant epilepsy patients with MTS by using
      the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL)
      method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin
      fragment, fractin. The temporal lobe specimens were obtained from 15 patients
      (six women and nine men; mean age, 29 +/- 8 years). RESULTS: Unlike that in
      normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining
      neurons dispersed throughout the hippocampus proper as well as in most of the
      reactive astroglia. Bax immunopositivity was increased in almost all neurons.
      Fractin immunostaining, an indicator of caspase activity, was detected in
      approximately 10% of these neurons. Despite increased Bax expression and
      activation of caspases, we could not find evidence for DNA fragmentation by TUNEL
      staining. We also could not detect typical apoptotic changes in nuclear
      morphology by Hoechst-33258 or hematoxylin counterstaining. CONCLUSIONS: These
      data suggest that either apoptosis is not involved in cell loss in MTS, or a very
      slow rate of cell demise may have precluded detecting TUNEL-positive neurons
      dying through apoptosis. Increased Bax expression and activation of caspases
      support the latter possibility.

PMID- 12790891
TI  - Expression and cell distribution of group I and group II metabotropic glutamate
      receptor subtypes in taylor-type focal cortical dysplasia.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is known to be a major cause of
      intractable epilepsy. The cellular mechanism(s) underlying the epileptogenicity
      of FCD remain largely unknown. Because recent studies indicate that metabotropic
      glutamate receptor subtypes (mGluRs) play a role in epileptogenesis, we
      investigated the expression and cellular distribution pattern of mGluRs in FCD
      specimens. METHODS: Immunocytochemical expression of group I and group II mGluR
      subtypes was investigated in 15 specimens of human FCD obtained during epilepsy
      surgery. RESULTS: Strong mGluR1alpha and mGluR5 (group I mGluRs) immunoreactivity
      (IR) was observed in the majority of FCD specimens in dysplastic as well as in
      heterotopic neurons. mGluR1alpha was expressed in a subpopulation of neurons
      (mainly large dysplastic cells), whereas mGluR5 was represented in a higher
      percentage of dysplastic neuronal cells. Group II mGluRs (mGluR2/3) IR was
      observed less frequently than that in group I mGluRs and generally appeared in
      <10% of the dysplastic neurons. IR for all three mGluR subtypes was observed in
      balloon cells. mGluR2/3 appeared to be most frequently expressed in glial
      fibrillary acidic protein (GFAP)-positive balloon cells (glial type), and
      mGluR1alpha, in microtubule-associated protein (MAP)2-positive cells (neuronal
      type). mGluR5 was present in the majority of balloon cells. Occasionally glial
      mGluR1alpha IR was observed in bizarre glial cells with di- or multinuclei.
      Reactive astrocytes were intensively stained, mainly with mGluR5 and mGluR2/3.
      CONCLUSIONS: The cellular distribution of mGluR subtypes, with high expression of
      mGluR1alpha and mGluR5 in dysplastic neurons, suggests a possible contribution of
      group I mGluRs to the intrinsic and high epileptogenicity of dysplastic cortical
      regions.

PMID- 12790892
TI  - Increased frequency of interleukin-1beta-511T allele in patients with temporal
      lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion.
AB  - PURPOSE: To confirm the high frequency of interleukin (IL)-1beta-511T allele
      occurrence in patients with temporal lobe epilepsy (TLE) and hippocampal
      sclerosis (HS), with special attention given to the impact of prolonged febrile
      convulsions (PFCs) on IL-1beta genotype distribution. METHODS: Patients with
      evidence of unilateral HS on magnetic resonance (MR) images were chosen as study
      subjects (TLE+HS; n = 66). Other patients with essentially normal MRI findings or
      only foreign tissue (TLE without HS; TLE-HS; n = 64), and those with symptomatic
      localization-related epilepsy but without TLE (SLE; n = 89) were selected as
      disease controls. A single base pair polymorphism at position 2511 in the
      promoter region of the IL-1beta gene was analyzed. RESULTS: The distribution of
      IL-1beta-511 genotypes as well as allele frequency was significantly different
      between TLE+HS patients and controls. In contrast, no difference was found
      between TLE-HS patients and controls or between SLE patients and controls.
      Further, in the group of patients with TLE+HS, the frequency of the IL-1beta-511T
      allele tended to increase as a function of febrile convulsions [0.531 without
      either PFC or simple febrile convulsion (SFC); 0.633 with SFC; 0.686 with PFC].
      Although no statistically significant difference was noted between patients
      without PFC and the controls, a chi2 analysis of allele distribution revealed a
      significant difference between those with PFC and the controls. CONCLUSIONS: PFC
      proved to be a potent determinant of IL-1beta-511T allele frequency; thus a
      discrepancy of PFC incidence should be considered an explanation of recent
      conflicting results regarding the association between the gene polymorphisms of
      IL-1beta-511 and TLE+HS.

PMID- 12790893
TI  - Hippocampal deformation-based shape analysis in epilepsy and unilateral mesial
      temporal sclerosis.
AB  - PURPOSE: To assess shape changes in patients with mesial temporal sclerosis (MTS)
      and temporal lobe epilepsy (TLE), by using deformation-based hippocampal shape
      analysis. METHODS: We retrospectively reviewed magnetic resonance imaging (MRI)
      studies in 30 subjects with unilateral MTS (15 right-sided MTS, 15 left-sided
      MTS) and TLE. We defined the "average" hippocampus in the right- and left-MTS
      groups by generating a mean transformation for the 15 deformation images in each
      group. Further to quantify the difference between the hippocampi, we coregistered
      the mean transformation of the involved hippocampus (with MTS) to the
      contralateral hippocampus, considering the left- and right-MTS groups
      independently. We generated a color "flame" scale showing degrees of outward and
      inward deviation of the coregistered hippocampi. RESULTS: Both the right- and
      left-MTS groups showed similar shape changes, with maximal inward deformation in
      the medial and lateral hippocampal head and the hippocampal tail. However, more
      extensive involvement was seen in the lateral hippocampal body in the right-MTS
      group as compared with the left. CONCLUSIONS: Deformation-based hippocampal shape
      analysis shows specific regions of hippocampal surface anatomy that are most
      affected in MTS. This technique may aid in detection of clinically significant
      anatomic abnormalities of the hippocampus in patients with epilepsy.

PMID- 12790894
TI  - Clinical and neuroimaging features of good and poor seizure control patients with
      mesial temporal lobe epilepsy and hippocampal atrophy.
AB  - PURPOSE: Hippocampal atrophy (HA) and signal changes, detected at magnetic
      resonance imaging, have been associated with intractable seizures. Such a
      relation has been established by tertiary centers, where the prevalence of more
      severe cases tends to be higher. We evaluated the clinical and imaging variables
      that may have relevance to seizure control in patients with mesial temporal lobe
      epilepsy (MTLE) and HA. METHODS: MTLE patients from the outpatient clinic of
      University of Sao Paulo School of Medicine at Ribeirao Preto were evaluated with
      protocols for the temporal lobe. Patients were considered to have good seizure
      control (GC; n = 42) if they had three of fewer seizures per year. Patients with
      pharmacoresistance and who did not fit the criteria for GC were considered to
      have poor seizure control (PC; n = 44). We made group comparisons and
      correlations of clinical data and hippocampal volume (HV) with seizure frequency.
      RESULTS: No statistical differences were observed between the GC and PC groups in
      the following parameters: age at the time of study, age at the time of the
      initial precipitating injury (IPI) or first epileptic seizure, epilepsy duration
      and follow-up, and family history of epilepsy. No differences were found in HV
      between GC (male, 2.04 +/- 0.60 cc; female, 2.00 +/- 0.70 cc) and PC (male, 2.26
      +/- 0.47 cc; female, 2.15 +/- 0.48 cc) groups. Regression analysis indicated no
      correlation between seizure frequency and HV (p = 0.33). CONCLUSIONS: These
      findings suggest that the intensity of HA does not have a direct correlation with
      seizure frequency in patients with MTLE with HA and that the detection of HA in
      MTLE patients does not mean an unequivocal indication of intractability.

PMID- 12790895
TI  - Myoinositol abnormalities in temporal lobe epilepsy.
AB  - PURPOSE: This study used magnetic resonance spectroscopy (MRS) to examine
      metabolite abnormalities in the temporal and frontal lobe of patients with
      temporal lobe epilepsy (TLE) of differing severity. METHODS: We investigated
      myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO
      TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short
      echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and
      analyzed by using LCModel. RESULTS: The temporal lobe ipsilateral to seizure
      origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated
      myoinositol (MI; HS-TLE NA, 7.8 +/- 1.9 mM, control NA, 9.2 +/- 1.3 mM; p < 0.05;
      HS-TLE MI, 6.1 +/- 1.6 mM, control mI 4.9 +/- 0.8 mM, p< 0.05). Frontal lobe MI
      was low in both patient groups (LO-TLE, 4.3 +/- 0.8 mM; p < 0.05; HS-TLE, 3.6 +/
      .05 mM; p < 0.001; controls, 4.8 +/- 0.5 mM). Ipsilateral frontal lobes had lower
      MI (3.8 +/- 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 +/- 0.8 mM; p
      < 0.05). CONCLUSIONS: MI changes may distinguish between the seizure focus, where
      MI is increased, and areas of seizure spread where MI is decreased.

PMID- 12790896
TI  - The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor
      outcome and neurosurgical aspects.
AB  - PURPOSE: To describe the histologic spectrum and clinical characteristics of
      patients with neuroepithelial tumors and drug-resistant epilepsy and to analyze
      clinical data and treatment related to seizure outcome and survival. METHODS:
      Data were analyzed from 207 consecutive patients with intractable epilepsy (aged
      2-54 years), who between 1988 and 1999 had >or=50% resection of supratentorial,
      neuroepithelial tumors. Extent of resection was assessed on postoperative
      magnetic resonance imaging (MRI); seizure outcome was classified according to
      Engel's outcome scale; and follow-up data were prospectively updated. RESULTS:
      Median follow-up was eight years (range, 2-14 years). Histologic examination
      revealed 154 classic epilepsy-associated tumors (ganglioglioma, dysembryoplastic
      neuroepithelial tumor, pleomorphic xanthoastrocytoma, and pilocytic astrocytomas)
      and 53 others (astrocytomas and oligodendrogliomas). Four World Health
      Organization (WHO) grade III tumors were found (astrocytoma, n = 3;
      ganglioglioma, n = 1). After surgery, 82% of the patients were seizure free
      (class I). The following factors were associated with improved seizure outcome:
      Short duration of epilepsy before surgery, single EEG focus, absence of
      additional hippocampal sclerosis or cortical dysplasia, transsylvian approach,
      other than astrocytomas, and complete tumor resection. After 5 years, only nine
      (4%) patients had tumor recurrence, four (2%) with malignant transformation and
      death. None of the four patients with anaplastic tumors died. Even patients with
      astrocytomas of WHO grade II or III showed 10-year recurrence of only 25% and 10
      year survival of 90%. CONCLUSIONS: Tumors associated with long-term epilepsy
      should be removed early for two different reasons: high rate of seizure freedom
      and rare but potential risk of malignant tumor progression. The unexpected long
      survival of these astrocytomas should be investigated by using
      immunohistochemistry and molecular biology.

PMID- 12790897
TI  - Acute postoperative seizures after frontal lobe cortical resection for
      intractable partial epilepsy.
AB  - PURPOSE: To evaluate the incidence and prognostic importance of acute
      postoperative seizures (APOSs) occurring in the first week after a focal
      corticectomy in patients with partial epilepsy of frontal lobe origin. METHODS:
      We retrospectively evaluated 65 patients who underwent a frontal lobe cortical
      resection for intractable partial epilepsy between April 1987 and December 2000.
      All patients were followed up for a minimum of 1 year after surgery. RESULTS:
      APOSs occurred in 17 (26%) patients. None of the following factors was shown to
      be significantly associated with the occurrence of APOSs: gender, duration of
      epilepsy, etiology for seizure disorder, use of subdural or depth electrodes,
      surgical pathology, or postoperative risk factor for seizures. Patients with
      APOSs were older at seizure onset and at the time of surgery (p = 0.003 and p =
      0.05, respectively). At last follow-up, patients who had APOSs had a seizure-free
      outcome similar to that of individuals without APOSs (47.1% vs. 50.0%; p = 0.77).
      Patients with APOSs appeared less likely to have a favorable outcome [i.e., fewer
      than three seizures per year and >95% decrease in seizure activity (58.8 vs.
      70.8%; p = 0.35)]. This result may not have reached statistical significance
      because of the sample size. No evidence suggested that precipitating factors or
      the timing of APOSs was an important prognostic factor. CONCLUSIONS: The presence
      of APOSs after frontal lobe surgery for intractable epilepsy does not preclude a
      significant reduction in seizure tendency. These findings may be useful in
      counseling patients who undergo surgical treatment for frontal lobe epilepsy.

PMID- 12790898
TI  - Obstructive sleep apnea in a clinical series of adult epilepsy patients:
      frequency and features of the comorbidity.
AB  - PURPOSE: The aim of this study was to evaluate the rate and features of
      obstructive sleep apnea (OSA) in adult epilepsy patients. METHODS: Two hundred
      eighty-three adult epilepsy patients (137 men; mean age, 33 years; range, 18-70
      years) were prospectively screened for OSA by means of a structured interview.
      Those in whom OSA was clinically suspected were monitored for a full night by
      using a portable device (Polymesam), and OSA was diagnosed when they had an
      Apnea/Hypopnea Index greater than five. RESULTS: Coexistence of OSA with epilepsy
      was found in 10.2% (15.4% of the male and 5.4% of the female) epilepsy patients
      investigated. The OSA was mild in 66.6%, moderate in 22.2%, and severe in 11.1%
      of the cases. The "epilepsy + OSA" patients were older, heavier, more frequently
      male, and sleepier (p < 0.05) than those with "epilepsy only." Furthermore, they
      experienced their first seizure at an older age (p < 0.05). CONCLUSIONS:
      Systematic investigation reveals that OSA is frequent in epilepsy patients. The
      major risk factors for OSA in our epilepsy patients were the same as those
      typically found in the general population. Of the epilepsy-related factors, older
      age at onset of seizures appears to be significantly related to comorbidity with
      OSA (p < 0.05). The presence in epilepsy patients of these features should alert
      the clinician to the possibility of an underlying OSA.

PMID- 12790899
TI  - Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant
      inheritance in Alabama.

PMID- 12790900
TI  - The ketogenic diet: adolescents can do it, too.
AB  - PURPOSE: To determine both the efficacy of and compliance with the ketogenic diet
      in the adolescent population. METHODS: A retrospective study of 45 patients, aged
      12-19 years, consecutively enrolled in a ketogenic diet program from 1994 to
      2002, was performed. Thirty-seven patients were from The Johns Hopkins Medical
      Institutions; eight were from The University of Texas at Houston. Charts were
      reviewed, and patients were contacted by telephone. RESULTS: Six months after
      diet initiation, 28 (62%) of 45 remained on the ketogenic diet, with six (21%) of
      28 having 50-90% seizure reduction, and eight (29%) of 28 having >90%. At 12
      months, 20 (44%) of 45 remained on the diet, with seven (35%) of 20 having 50-90%
      seizure reduction and six (30%) of 20 achieving >90% efficacy. Only 22%
      discontinued the diet for perceived restrictiveness. The mean diet duration was
      1.2 years. Patients with multiple seizure types did best, whereas gender, prior
      seizure frequency, diet ratio, and age did not influence outcome. Patients
      dependent on parents for daily care were more likely to remain on the diet at 6
      months, but had less efficacy. Weight loss (60%) and menstrual dysfunction (45%
      of female subjects) were the most commonly reported side effects. CONCLUSIONS:
      The ketogenic diet is as well tolerated and efficacious for adolescents with
      epilepsy as for the general childhood population.

PMID- 12790901
TI  - Diffusion-weighted imaging abnormalities in the splenium after seizures.
AB  - PURPOSE: Transient increased T2 signal in the splenium of the corpus callosum
      after seizures has been reported and sometimes attributed to a postulated
      toxicity of anticonvulsant medications (AEDs). METHODS: We describe two patients
      with bitemporal epilepsy. RESULTS: Transiently increased T2 signal (in one) and
      decreased apparent diffusion coefficient (ADC) (in both) in the splenium appeared
      to be related directly to acute seizures. CONCLUSIONS: These cases illustrate an
      unusual acute postictal imaging finding, highlight involvement of an important
      commissural pathway, and suggest that seizures per se, and not their treatment,
      are the cause of transient white-matter abnormalities in these cases.

PMID- 12790902
TI  - Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or
      adverse effect of vagal nerve stimulation?
AB  - Sensory symptoms are commonly seen in association with focal epilepsy, but
      viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main
      clinical manifestation. With the introduction of vagal nerve stimulation (VNS)
      for medically refractory epilepsy, viscerosensory symptoms commonly occur as an
      adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local
      neck or throat pain, and cough are the most common adverse effects seen during
      active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a
      tingling sensation of the neck and throat is directly related to stimulation
      intensity. We present a case in which recurrent pharyngeal sensations caused a
      diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and
      correlating this with clinical symptoms helped determine the etiology of the
      recurrent sensory symptoms.

PMID- 12790903
TI  - Restricted frontomesial epileptogenic focus generating dyskinetic behavior and
      laughter.
AB  - PURPOSE: Substantial data are missing about the anatomic location of frontal
      regions supporting gelastic seizures. METHODS: We report the results of stereo
      electro-encephalographic recordings performed over several distinct functional
      premotor and executive fields in a patient whose seizures were characterized by
      dyskinetic behavior and ictal laughter, in the absence of cerebral MRI
      abnormalities. RESULTS: The epileptogenic zone was circumscribed in the anterior
      and ventral part of the supplementary motor area and the underlying dorsal
      cingulate cortex. There were no or little spreading to cortical neighboring
      areas. The patient is seizure-free (follow-up of 27 months) after a stereotactic
      electric radiofrequency lesion of the epileptogenic focus. CONCLUSION: The
      present data suggest that pericingulate premotor areas are involved in the
      triggering of the motor component of laughter. In this case, the coexistence of
      paroxysmal dyskinesias during laughter might reflect the involvement of specific
      compartment(s) of the basal ganglia.

PMID- 12790904
TI  - Interictal paroxysmal epileptic discharges during sleep in childhood: phenotypic
      variability in a family.
AB  - We report three children of the same parents who exhibited various types of
      cognitive disorders, ranging from severe mental deficiency with transient
      autistic-like regression to specific neuropsychological disabilities, associated
      with paroxysmal EEG abnormalities with various patterns of severity. This
      familial association highly suggests a genetic factor responsible for both
      epileptic discharges on EEG and cognitive dysfunction.

PMID- 12790905
TI  - Late language transfer in patients with Rasmussen encephalitis.

PMID- 12790906
TI  - Development of temporal lobe epilepsy in 21-day-old rats.

PMID- 12790910
TI  - Behavior problems in nonepileptic children with rolandic epileptiform discharges.

PMID- 12790908
TI  - Another Rett patient with a typical Angelman EEG.

PMID- 12790911
TI  - Quantitative venous severity scoring using venous arterial flow index by duplex
      sonography.

PMID- 12790913
TI  - Dysplasia in the ileoanal pouch.
AB  - Formation of an ileo-anal pouch is an accepted technique following colectomy in
      the surgical management of ulcerative colitis (UC) and familial adenomatous
      polyposis (FAP). The configuration of pouches and anastomotic techniques has
      varied over the last two decades. The increased use of stapling devices in
      formation of the pouch-anal anastomosis avoids the need for endoanal mucosal
      stripping and may contribute to improved functional results, but leaves a
      'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long
      term safety of the ileo-anal pouch have been raised by reports of the occurrence
      of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC,
      persistence of underlying disease in the residual rectal mucosa, anal transition
      zone and columnar cuff provides the site for development of dysplasia and
      malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy,
      as long-term follow-up of patients with Koch pouches has demonstrated. In FAP,
      any persistent rectal mucosa and mucosa of the small intestine is at risk of
      adenomatous dysplasia due to the genetic alterations causing the disease. Long
      term surveillance should focus on all FAP pouch patients, and in UC patients
      should be directed towards the diagnosis of residual rectal mucosa in the area
      distal to the pouch anastomosis. Specialist histopathological opinion is
      essential in the diagnosis of dysplasia in the ileo-anal pouch.

PMID- 12790914
TI  - The role of topical diltiazem in the treatment of chronic anal fissures that have
      failed glyceryl trinitrate therapy.
AB  - OBJECTIVE: The treatment of anal fissures has evolved over the last 5 years with
      the development of topical treatments aimed at reducing sphincter hypertonia.
      This is thought to improve anal mucosal blood flow and promote healing of the
      fissure. This study reports the use of topical diltiazem in patients with chronic
      anal fissures that have failed previous treatment with topical 0.2% glyceryl
      trinitrate (GTN). PATIENTS AND METHODS: Forty-seven patients with chronic anal
      fissure who had previously failed at least one course of topical GTN were
      recruited prospectively from a single centre. Patients were instructed to apply 2
      cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for
      eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear
      analogue score prior to starting the cream and then repeated at 2 weekly
      intervals. Patients were asked to report side-effects throughout the study
      period. Healing of the fissure was assessed after 8 weeks of treatment. RESULTS:
      Forty-six patients completed treatment; of these, 22 had healed fissures (48%).
      Ten of the 24 patients with persistent fissures were symptomatically improved and
      wished no further treatment. Of the 14 patients who remained symptomatic, one was
      given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the
      fissure, 10 were recruited into an ongoing study involving injections of
      botulinum toxin into the internal anal sphincter and three were referred for
      surgery. CONCLUSION: This study shows that topical 2% diltiazem is an effective
      and safe treatment for chronic anal fissure in patients who have failed topical
      0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.

PMID- 12790915
TI  - Pre-operative assessment of anal fistulas using endoanal ultrasound.
AB  - OBJECTIVE: To study the accuracy of endoanal ultrasound in pre-operative
      assessment of cryptoglandular anal fistulas, with respect to the site of the
      internal opening, type and depth of the fistula tract. PATIENTS AND METHODS: A
      consecutive series of 151 patients with anal sepsis underwent pre-operative
      endoanal ultrasound assessment of a suspected anal fistula. Hydrogen peroxide was
      used to define the tract when there was doubt as to the course of the fistula.
      All patients subsequently had surgical exploration under anaesthesia,
      irrespective of findings at sonography. The site of the internal opening, depth
      and type of fistula were recorded at surgery, and concordance with the ultrasound
      was assessed. RESULTS: One hundred and forty-five patients were subsequently
      shown to have a fistula at surgical exploration. Type of fistula: Two thirds were
      transsphincteric (63%) and one third were inter sphincteric (32%), with a few
      submucosal, and supra sphincteric fistulas. Ultrasound correctly predicted
      surgical findings in 82% of patients (124/151). Concordance was highest for
      transsphincteric fistulas (87%). Internal opening: Accuracy of predicting the
      site of the internal opening was 93% (140/151). The commonest site for the
      internal opening was the midline posteriorly (49%), followed by the midline
      anteriorly (25%), the rest lay laterally. Fistula depth: Ultrasound and surgical
      assessment of the depth of fistulas was concordant in 120 of 145 patients (83%).
      CONCLUSIONS: Endoanal ultrasound has a high accuracy of predicting the site of
      internal opening of an anal fistula. Endoanal ultrasound is able to assess the
      type and depth of a fistula. This information is useful for pre-operative
      planning of fistula treatment.

PMID- 12790916
TI  - Telomerase expression of malignant epithelial cells correlates with Dukes' stage
      in colorectal cancer.
AB  - BACKGROUND: The ribonucleoprotein telomerase has been proposed as a potential
      prognostic marker for malignancy. Whether telomerase activity of clinical
      specimens correlates with other clinico-pathological variables, however, remains
      controversial. This is at least in part due to the varying contribution that
      nonmalignant cells will make to the net activity when extracts are assayed for
      telomerase activity. We therefore designed experiments to assay telomerase
      activity of isolated malignant cells of primary colorectal cancers. METHODS:
      Thirty colorectal cancer and 20 corresponding specimen taken from macroscopically
      normal regions of the colon were mechanically disaggregated and digested with
      collagenase, DNase and hyaluronidase. The epithelial cell population was
      separated using Ber-EP4 pan-epithelial antibody and Magnetic Activated Cell
      Sorting technique. Haematoxylin and eosin staining was used to assess the
      proportion of recovered epithelial cells which were malignant. Telomerase
      activity was assayed by the Telomeric Repeat Amplification Protocol, which was
      quantified by PhosphorImager with Image Quant software. RESULTS: Epithelial cells
      of three of 20 normal mucosa specimens were telomerase positive with weak
      activity (mean 3.7 TPGs, Total Product Generated, range 1.4-5.1TPGs). In the
      cancer group the vast majority (>95%) of the epithelial cells recovered were
      malignant by cytological criteria. Epithelial cells were telomerase positive in
      all the cancers, with a wide range of telomerase activity values (mean 22.7 TPGs,
      range 0.19-308 TPGs). Telomerase activity correlated with Dukes' stage (r = 0.52,
      P=0.004, Spearman's rank). CONCLUSIONS: Pathological stage correlates with
      telomerase activity of the malignant cell population of the primary tumour in
      colorectal cancer. This suggests that telomerase activity increases during the
      progression of a cancer and may have implications for the design of anticancer
      (antitelomerase) agents.

PMID- 12790917
TI  - Intra-operative injection of Patent Blue V dye to facilitate nodal staging in
      colorectal cancer.
AB  - OBJECTIVES: Routine histopathology may understage colorectal cancer by failing to
      detect involved lymph nodes. This study examined the feasibility of dye staining
      those lymph nodes most likely to harbour metastases. PATIENTS AND METHODS: Patent
      Blue V dye 2.5% was injected intra-operatively into left-sided colorectal
      carcinomas prior to resection in 19 patients. RESULTS: Blue-stained nodes were
      found in 12/19 patients (63%). Examination of blue-stained nodes alone correctly
      identified overall nodal status in 11 (92%) of these 12 patients. CONCLUSION: The
      technique needs to be refined further. Nonetheless, intra-operative lymph node
      staining using blue dye offers the prospect of improving the ease and accuracy of
      nodal staging in colorectal cancer.

PMID- 12790918
TI  - The contemporary management of haemorrhoids.
AB  - BACKGROUND: New concepts in the management of haemorrhoidal disease have recently
      rekindled interest in this common pathology. General and subspecialist colorectal
      surgeons were surveyed to assess their impact on the current management of
      haemorrhoids. METHODS: A questionnaire was sent to all members of the Association
      of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of
      Surgeons of Great Britain and Ireland (ASGBI). Regarding indications for surgery,
      surgical techniques, day case haemorrhoidectomy (DCH) and postoperative treatment
      regimens. ASGBI members were asked to state their subspecialist interest and
      estimated time devoted to colorectal practice. RESULTS: There were 406 (71%)
      ACPGBI respondents and 483 (68%) ASGBI respondents. Eighty-four (12%) ASGBI
      respondents performed no elective colorectal surgery. One hundred and ninety-nine
      (35%) of ACPGBI respondents saw between 6 and 10 new haemorrhoid patients per
      week whereas three hundred (42%) of ASGBI respondents saw between 1 and 5 per
      week. Non-operative management included routine advice on fluid and diet by the
      majority of surgeons, with banding carried out in 79% (ACPGBI) and 75% (ASGBI)
      and injection sclerotherapy in 61% (ACPGBI) and 56% (ASGBI). The Milligan Morgan
      haemorrhoidectomy was performed in 265 (46%; ACPGBI) and 336 (47%; ASGBI). ACPGBI
      members used Submucosal diathermy (148, 26%vs 67, 9%; ASGBI (P < 0.01; chi2 test
      with Yates correction)) and stapled anoplasty (61, 11%vs 14, 2%; ASGBI (P < 0.01;
      chi2 test with Yates correction)) more often. DCH was performed in 117 (20%;
      ACPGBI) and in 48 (7%; ASGBI)(P < 0.01; chi2 test with Yates correction).
      CONCLUSIONS: In this sample of surgeons, operative management varies according to
      specialist interest. There was a trend towards day case haemorrhoidectomy. Whilst
      more surgeons have accepted the use of postoperative techniques to reduce pain,
      only a small minority have, as yet, adopted new surgical techniques such as
      stapling.

PMID- 12790919
TI  - Histological changes associated with the use of intravenous cyclosporin in the
      treatment of severe ulcerative colitis may mimic dysplasia.
AB  - BACKGROUND: During six years experience of intravenous cyclosporin (i.v. Cy) for
      severe ulcerative colitis we have noted that changes of villous architecture and
      epithelial regeneration occur even when the disease fails to enter clinical
      remission and colectomy is required. OBJECTIVE: To describe the histological
      changes in patients who received i.v. Cy and steroids compared with those treated
      with i.v. steroids alone. PATIENTS AND METHODS: Two groups of histological
      sections were reviewed. The first group was of 23 colectomy specimens from
      patients who had been treated with i.v. Cy and steroids. For 11 patients pre-Cy
      histological sections were available. The second group was of 10 colectomy
      specimens from patients who had received i.v. steroids alone. Biopsies were
      scored for their histological disease activity (HDAI), villous architecture and
      epithelial regeneration. The HDAI assesses the degree of acute and chronic
      inflammation. RESULTS: The post-Cy group had higher median scores for villous
      architecture and epithelial regeneration compared to the pre-Cy and poststeroid
      groups. For the patients where both pre- and post-Cy histological sections were
      available 63% increased their villous score post-Cy and 82% increased their
      epithelial regeneration score post-Cy. CONCLUSION: Although villous
      transformation and epithelial regeneration may be seen in UC they are more
      frequent and more severe in those patients who received i.v. Cy and i.v.
      steroids, compared to controls who received i.v. steroids alone. These
      histological changes may mimic dysplasia. Increased awareness of this potential
      mimic of dysplasia is crucial for patient management.

PMID- 12790920
TI  - Diagnostic lessons learnt from a series of enterovesical fistulae.
AB  - OBJECTIVE: An enterovesical fistula (EVF) is an uncommon condition requiring
      careful and sometimes extensive preoperative investigation. Our experience over a
      10-year period has been reviewed with emphasis on the diagnostic investigations
      performed. PATIENTS AND METHOD: Forty-two patients (30 male) have been studied.
      Presenting symptoms, diagnostic investigations, and subsequent treatment have
      been reviewed. RESULTS: The site of the fistulae were; 37 colonic, 2 rectal, and
      3 ileal. The commonest presenting symptoms were; pneumaturia 75%, faecaluria 63%
      and urinary tract infections 57%. The positivity rate of the investigations
      performed were; cystoscopy 89%, urine cytology 86%, barium enema 65%,
      computerized tomography (CT) scanning 55%, IVP 35%, and cystography 27.5%. The
      causes of the fistula were; diverticular disease 71%, carcinoma 20%, Crohn's
      disease 7%, and radiotherapy 2%. CONCLUSIONS: We recommend cystoscopy and urine
      cytology for faecal material as the first-line investigations in all patients
      with a suspected enterovesical fistulae. CT scanning and barium enema should not
      be first line investigations but may be performed subsequently to help determine
      the aetiology and planning of surgery.

PMID- 12790921
TI  - Treatment of resistant anal fissure with advancement anoplasty.
AB  - OBJECTIVE: The primary aim of this study was to assess the outcome of advancement
      anoplasty in the treatment of chronic anal fissure, resistant to conventional
      therapy. The secondary aim was to evaluate the anal resting pressure in these
      patients with resistant fissures. PATIENTS AND METHODS: Over a five-year period
      eight patients (2 male, median age 55 years, range 20-74) with resistant anal
      fissure were referred from 6 centres. They had endured symptoms for a median of 8
      years (range 2-20) and had undergone a median of 2 previous surgical procedures
      (range 1-3), including lateral sphincterotomy and anal dilatation. Anorectal
      physiological testing was performed on all patients who then underwent
      advancement anoplasty. The outcome was analysed retrospectively. RESULTS: Pre
      operative anorectal physiological testing showed a significantly lowered median
      maximal anal resting pressure of 42 mm H2O (range 12-72 mm H2O, normal range > 60
      mm), P=0.03. All patients underwent advancement anoplasty. At a median of seven
      months follow-up (range 2-22) seven of eight patients had healed their fissure
      and were asymptomatic. The median healing time was four months (range 2-6).
      CONCLUSION: Patients with chronic anal fissure, resistant to conventional
      therapy, may be successfully treated by advancement anoplasty. Healing time
      however, may be prolonged. In this series patients had a decreased anal resting
      pressure rather than anal hypertonia.

PMID- 12790922
TI  - Transanal endoscopic microsurgery--lessons from a single UK centre series.
AB  - OBJECTIVES: Transanal endoscopic microsurgery (TEM), a minimally invasive
      technique has been employed in the excision of benign and selected malignant
      rectal tumours since 1983. We present a single surgeon's series of 102
      procedures. PATIENTS AND METHODS: A retrospective case note review of 102
      procedures performed over a 6-year period between 1996 and 2001. RESULTS: One
      hundred and two TEM procedures were performed on 100 patients. 68 for adenomas,
      19 potentially curative excisions for carcinoma, 13 palliative procedures for
      advanced carcinoma and 2 for solitary rectal ulcer syndrome (SRUS). Four adenomas
      recurred and were successfully treated by various procedures. None went on to
      develop malignancy, or a further recurrence. Of the cancers, six T1 and 10 T2
      were excised with curative intent. Three T3 cancers were excised before
      endorectal ultrasound was available in the unit and went on to have definitive
      procedures. One T1 and two T2 carcinomas were not completely histologically
      excised. These patients were offered definitive procedure and there have been no
      recurrences. 11 patients underwent palliative TEM procedures, 2 went on to have a
      recurrence of symptoms. Both underwent a successful second TEM procedure.
      CONCLUSIONS: Although longer term follow up is still required, TEM appears to be
      an effective method of excising benign tumours and T1 carcinomas of the rectum.
      The role of TEM in the treatment of T2 carcinomas is, as yet, unclear and needs
      further evaluation although the results of our series and others are encouraging.

PMID- 12790923
TI  - Histopathology of stapled haemorrhoidectomy specimens: a cautionary note.
AB  - OBJECTIVE: Stapled haemorrhoidectomy is a new technique with encouraging early
      results. The aim of this study was to examine the tissue removed during stapled
      haemorrhoidectomy, in particular to check on the presence or absence of
      transitional or squamous anal canal mucosa and internal anal sphincter muscle.
      METHODS: Twenty-six consecutive patients undergoing stapled haemorrhoidectomy
      were studied. Resected tissue was examined histologically according to a
      standardized histological protocol. RESULTS: All 26 specimens contained columnar
      mucosa. Twelve specimens also contained anal transitional and stratified squamous
      epithelium. Two specimens contained columnar and transitional mucosa. Twenty-two
      of 26 specimens contained smooth muscle as well as mucosa (median maximum
      diameter 7.5 mm, range 2-20 mm). In 11 specimens this was circular muscle only;
      in 11 circular and longitudinal smooth muscle were present. In 10 specimens
      smooth muscle was seen to be lying beneath stratified squamous or transitional
      epithelium, suggesting that it was from the internal anal sphincter. CONCLUSIONS:
      Stapled haemorrhoidectomy results in resection of stratified squamous mucosa or
      part of the internal anal sphincter in a significant proportion of patients.
      Surgeons should be aware that this technique may result in damage to the internal
      anal sphincter.

PMID- 12790924
TI  - Treatment of constipation in adults associated with idiopathic megarectum by
      behavioural retraining including biofeedback.
AB  - BACKGROUND: Constipation in adults associated with a grossly dilated rectum and
      recurrent faecal impaction, idiopathic megarectum, is rare. The aetiology of
      idiopathic megarectum is unknown, but may involve neuromuscular or behavioural
      factors. It is unknown whether the condition is reversible. This study aimed to
      determine the efficacy of behavioural therapy, including biofeedback, in such
      patients. METHODS: Six patients (4 female; median age 27) with a history of
      rectal faecal impaction and a grossly dilated rectum on radiological examination
      were evaluated by structured questionnaire before, immediately after biofeedback
      therapy, and on follow-up. Physiological testing was performed before treatment,
      and 2 patients were evaluated by repeat physiological testing and contrast
      radiology on follow-up. RESULTS: On median follow-up of 18 months (range 11-27),
      five patients felt major and one patient minor improvement in symptoms, including
      two with complete symptom relief. Four patients came off laxatives without
      recurrent faecal impaction. In the 2 studied patients rectal size did not appear
      to decrease. CONCLUSION: Behavioural retraining, including biofeedback, improved
      symptoms in most patients with idiopathic megarectum. In some patients symptoms
      completely resolved, without the need for laxatives. Although further studies are
      necessary in terms of both larger number of patients and longer follow-up period,
      behavioural treatment may be useful for such patients.

PMID- 12790925
TI  - The impact of bowel cancer awareness week.
AB  - OBJECTIVES: To assess knowledge of Bowel Cancer Awareness Week (BCAW) amongst
      patients attending their general practice surgery and to identify whether BCAW
      could increase knowledge of colorectal cancer symptoms. METHOD: Questionnaire
      study with ethics committee approval. Patients attending non-emergency clinics in
      a single general practice during the week following BCAW were given a
      questionnaire. Respondents were asked for knowledge of colorectal cancer
      symptoms, sources of this information and awareness of BCAW compared to similar
      knowledge of breast cancer. RESULTS: Seventy-seven patients responded (96%
      response rate, median age 42, 40% male). Eighty-five percent could name a breast
      cancer symptom compared to only 44% who could name a colorectal cancer symptom
      (McNemar's chi2, P < 0.0001). Respondents identified more sources of information
      for breast than colorectal cancer. Only 21% had heard of BCAW and none could name
      any symbol for bowel cancer awareness whereas 69% were aware of Breast Cancer
      Awareness Month and 28% could name its symbol (McNemar's chi2, P < 0.0001).
      Multivariate analysis demonstrated that patients who were aware of BCAW were 4.6
      times more likely to have knowledge of colorectal cancer symptoms (95% CI 1.25
      17.1). CONCLUSIONS: Despite their similar incidence, knowledge of colorectal
      cancer is much less than breast cancer. In part this may be due to the greater
      publicity given to breast cancer. BCAW can increase knowledge of colorectal
      cancer symptoms but currently, too few people are aware of it.

PMID- 12790926
TI  - Carcinomatous transformation in hyperplastic polyps of the colon and rectum.

PMID- 12790927
TI  - Femoral nerve palsy after colorectal surgery.

PMID- 12790932
TI  - Surgical resection of colorectal liver metastases.
AB  - BACKGROUND: Liver metastases are a major cause of death in patients with
      colorectal carcinoma. The only curative option available at present is surgery.
      This review article discusses the current state of evidence for the effectiveness
      of liver resection for patients with liver metastases from colorectal cancer.
      METHODS: Medline, Embase, Current Contents and Science Citation Index databases
      were used to search English language articles published on the subject of liver
      resection for colorectal metastases in the last 20 years. RESULTS: Liver
      resection has a five year survival of 16-49% and 10 year survival of 17-33% with
      an operative mortality rate of 0-9%. Two factors appear to be clearly associated
      with poorer outcome - involved resection margins and the presence of extrahepatic
      disease (including hilar and coeliac axis lymph nodes) at the time of liver
      resection. None of the other factors related to the patients, their primary
      tumour or the metastases themselves have been conclusively shown to adversely
      effect long-term survival. CONCLUSIONS: Liver resection is a feasible, safe and
      effective procedure which carries an acceptable morbidity and mortality and does
      have a major impact on the survival of these patients. The decision on
      resectability of colorectal metastases should be decided by the ability to leave
      at least 2-3 segments of liver free from metastases with uninvolved resection
      margins, together with the general fitness of the patient to undergo a major
      surgical procedure.

PMID- 12790933
TI  - Circular stapled anopexy for haemorrhoidal disease: results.
AB  - OBJECTIVE: Stapled anopexy is a new approach for haemorrhoids requiring surgical
      treatment. This study reviews the available information concerning the present
      results of this procedure. METHODS: Medline and hand search of the literature was
      conducted to identify available information on the procedure, with a special
      interest for the on-going or published randomized clinical trials. RESULTS: The
      advantages of the stapled approach of haemorrhoids were analyzed in the different
      areas of concern, including postoperative pain reduction, length of hospital stay
      and sick-leave, postoperative wound care and type and rate of complications.
      Continence status, symptom cure and patient satisfaction following stapled
      anopexy are also reported. CONCLUSION: Stapled anopexy is probably less painful
      than conventional haemorrhoidectomy. Other advantages in the short term result
      from this new approach. Long term efficacy of the procedure is still unknown.

PMID- 12790934
TI  - Immunoscintigraphy and intra-operative radioimmunodetection in the treatment of
      colorectal carcinoma.
AB  - PURPOSE: Intra-operative radioimmunodetection of malignant involved lymph nodes
      follows the pre-operative immunoscintigraphy in the treatment of patients with
      colorectal carcinoma. The aims of this clinical study were to determine the
      sensitivity of the method, to compare the results in study when using Oncoscint
      and CEA-Scan and to evaluate the importance of the method of surgery and
      postoperative adjuvant therapy. PATIENTS AND METHODS: 121 patients with
      colorectal tumours (106 primary and 15 recurrent) were operated on using
      radioimmunoguided surgery (RIGS). The study compared results of pre-operative
      immunoscintigraphy, intra-operative radioimmunodetection and postoperative
      histological examination. Histological investigation used classical H&E staining.
      In histologically negative and RIGS positive cases the immunohistochemical
      investigation was supplemented. Two radiopharmaceuticals were used Oncoscint CR
      103 (MAb B72.3, Satumomab Pendetide), labelled with 111In in 56 patients and CEA
      Scan (IMMU 4-Fab' fragments MAb against CEA, Arcitumomab), labelled with 99mTc in
      65 patients. RESULTS: The relationship between RIGS positive results and
      histological examination was statistically assessed after 38 operations and the
      most acceptable RIGS evaluating index was determined. All subsequent results were
      evaluated by this index. Immunoscintigraphy of tumour was positive in 112 cases
      (92.6%). Fifty-five RIGS positive cases of malignant infiltrated lymph nodes were
      confirmed by 43 histologically positive examinations (78%). In this group 9 cases
      were discovered only by immunohistochemistry. Sixty-six remaining RIGS negative
      results were confirmed in 62 (94%) cases by negative histology. CONCLUSIONS: Both
      immunoscintigraphy and RIGS enable one to make a more accurate diagnosis. While
      treating the primary disease the use of RIGS may help in assessment of necessary
      extent of operation performance and in staging of the disease by revealing occult
      lymph nodes involved. Pre-operative immunoscintigraphy seems to be a useful
      diagnostic method for detection of tumour recurrence. When comparing two
      radiopharmaceuticals used, CEA-Scan seems to be more suitable for diagnostic
      studies, but using the Oncoscint for tumour recurrence detection had some
      specific benefit, too.

PMID- 12790936
TI  - Long-term results of subtotal colectomy for severe slow-transit constipation in
      patients with normal rectal function.
AB  - OBJECTIVE: The outcome of subtotal colectomy for severe constipation may be
      difficult to predict. One factor, which probably is of major importance for the
      functional outcome, is rectal function. The aim of the study has been to evaluate
      long-term results after subtotal colectomy with ileo-rectal anastomosis in a
      group of patients with severe slow-transit constipation but without evidence of
      impaired rectal emptying. PATIENTS AND METHODS: Of 273 patients with constipation
      referred for surgical evaluation 18 (7%) fulfilled our criteria for subtotal
      colectomy. Slow-transit was confirmed by radio-opaque marker studies and normal
      rectal function by emptying of viscous fluid and normal emptying at defecography.
      RESULTS: At follow up between 3 and 9 years 15 patients had a bowel frequency
      between 2 and 6 daily. One patient, who had an ileostomy because of anastomotic
      leak, had not wanted bowel continuity restored. One patient with opiate abuse
      became less constipated with 2-3 bowel movements a week. One patient was still
      constipated one year after the operation and subsequently had an ileal pouch-anal
      anastomosis. This patient who had normal rectal emptying had a very high volume
      tolerability with a maximum tolerable volume of 700 ml. In 4 of 7 patients
      abdominal pain persisted after the operation, and 3 developed diarrhoea, which
      required daily intake of loperamide. CONCLUSION: Subtotal colectomy for severe
      slow-transit constipation is justified provided anorectal function is normal. In
      spite of normal rectal emptying very high rectal volume tolerability may be an
      indicator of functional megarectum and impaired rectal emptying postoperatively.

PMID- 12790935
TI  - Island flap perineoplasty decreases the incidence of wound breakdown following
      overlapping anterior sphincter repair.
AB  - OBJECTIVE: Overlapping anterior sphincter repair is the accepted treatment for
      faecal incontinence resulting from sphincter disruption, however, wound breakdown
      has been reported to occur in up to 30% of patients. The aim of this study was to
      assess whether the type of wound closure affected the incidence of wound
      breakdown, and in particular whether island flap perineoplasty decreased this
      incidence. METHODS: An historical control study was performed evaluating wound
      outcomes in patients undergoing different methods of wound closure after
      sphincter repair. Data were obtained from a prospectively collected database.
      RESULTS: 85 patients who underwent overlapping sphincter repair were studied.
      Five patients had their wounds left open to heal by granulation. Of the remaining
      80 patients, wound dehiscence occurred in 33 patients (41%). When wound breakdown
      did occur, the mean time to healing was 9.1 weeks. Wound dehiscence was found to
      occur significantly less frequently in patients having an island flap
      perineoplasty than in those having other forms of wound closure (15 vs 54%;
      P=0.0015). The presence of a complex injury such as cloacal defect or recto
      vaginal fistula was also found to increase the incidence of wound breakdown,
      however, performing additional operations at the time of sphincter repair such as
      levator-plasty, gynaecological procedures or defunctioning colostomy did not
      affect the incidence of wound disruption. CONCLUSIONS: Wound disruption following
      overlapping anterior sphincter repair occurs in a significant proportion of
      patients and results in prolonged healing. Island flap perineoplasty
      significantly decreases the incidence of wound disruption in comparison to other
      forms of wound closure.

PMID- 12790937
TI  - Colorectal subspecialization in a DGH. The way forward!
AB  - AIMS: To audit all aspects of the diagnosis and management of colorectal cancers
      by a specialist unit within a District General Hospital (DGH). To compare the
      clinical effectiveness of the specialist service with the service prior to
      specialization and attempt to assess the feasibility of setting up such a service
      within the constraints imposed by a DGH. MATERIALS AND METHODS: Data for this
      study was collected prospectively over a 3-year period from July 1997 to June
      2000 since the establishment of a specialist colorectal service. The results so
      obtained have been compared with the Trent and Wales audit of 1993 as well as
      with the guidelines issued by the Royal College of Surgeons of England and the
      Association of Colo-proctologists of Great Britain and Ireland. We have attempted
      to evaluate whether specialization has altered the outcome for patients with
      colorectal cancer. RESULTS: A total of 2181 patients were seen at the specialist
      colorectal clinic and 42% underwent immediate flexible sigmoidoscopy. A total of
      241 colorectal cancers were diagnosed during this period by the specialist unit,
      of which the rapid access clinic had picked up 191 (a pick-up rate of 8.75%). The
      mean age of patients with colorectal cancer was 69.23 years and the median
      waiting time from referral to clinic and from referral to treatment was 9 days
      and 24 days, respectively. These compare favourably with the waiting times prior
      to specialization. 117 rectal cancers were diagnosed of whom 32 (32%) underwent
      APER. A selective approach to short course preoperative radiotherapy resulted in
      24% of rectal cancer patients receiving this treatment. The CRM was positive in
      14% of resected rectal cancers, all of whom had received preoperative
      radiotherapy. The percentage of patients with Dukes' stage A disease has risen
      from 11% in 1993 to 23% and the percentage of patients undergoing emergency
      surgery have fallen from 29% in 1993 to 8.2%. The rate of permanent stoma
      formation has also decreased from 52% to 32%. This audit has also confirmed that
      the guidelines for the management of colorectal cancers were all being met or
      exceeded. CONCLUSION: The study demonstrates that, even within the constraints of
      a DGH, a specialist service can result in earlier diagnosis, shorter waiting
      periods and judicious use of adjuvant treatment leading to improved clinical
      effectiveness. It is possible to deliver a high quality service, which meets, and
      in some areas, surpasses the minimum guidelines, provided there is an integrated
      multidisciplinary approach.

PMID- 12790938
TI  - The efficacy of chemoradiation therapy in HIV seropositive patients with squamous
      cell carcinoma of the anus.
AB  - OBJECTIVE: The aim was to assess the efficacy of chemoradiation therapy for
      squamous cell carcinoma of the anal canal in HIV seropositive patients. PATIENTS
      AND METHODS: A retrospective review of all patients with squamous cell carcinoma
      of the anus treated primarily with combined chemotherapy (5-fluorouracil and
      mitomycin) and radiotherapy or local excision was undertaken comparing HIV
      seropositive to HIV seronegative patients. RESULTS: Thirteen HIV seronegative
      patients were compared with 6 HIV seropositive patients. The HIV positive group
      included a higher proportion of males and a significantly greater history of
      prior treatment for condyloma. There was no difference in the median radiation
      dose (5020 cGy vs 4500 cGy, P=0.10). There was a trend towards higher local
      tumour recurrence in the HIV seropositive patients although this was not
      statistically significant (30% vs 66%). The CD4 count of HIV positive patients
      did not correlate either with their ability to complete the prescribed treatment
      regimen or with subsequent recurrence. CONCLUSION: Combined chemoradiation is
      feasible in HIV positive patients, however, local recurrence rates in HIV
      positive patients may be higher. Tolerance of this therapy in HIV seropositive
      patients or recurrence after therapy are not related to the patient's CD4 cell
      count.

PMID- 12790939
TI  - Success and failure after repair of rectovaginal fistula in Crohn's disease:
      analysis of prognostic factors.
AB  - OBJECTIVE: To compare the healing rate after several types of surgical repair of
      rectovaginal fistula (RVF) in Crohn's disease, and to identify factors predicting
      a successful outcome. PATIENTS AND METHODS: A Medline review of the literature
      since 1980 and analysis of our results in 32 consecutive patients was done.
      RESULTS: All types of repair (rectal, vaginal, anocutaneous advancement flap, or
      perineoproctotomy with fistula closure) seem to be equally effective. Healing
      after a first repair is observed in 58 (46-71)%. Healing can still be obtained at
      subsequent attempts in 62 (40-71)% of the patients. The reported overall healing
      rate is 75 (56-93)%. The need for proctectomy after an attempt to repair was 6 (0
      27)% in these series. Using a tailored surgical approach, we observed primary
      healing in 57%, healing after one or more supplementary procedures in 71%, for a
      total 'definitive' closure rate of 75%. Anal continence was never compromised and
      all temporary stomas (12 patients) could be closed. Univariate analysis
      identified number of Crohn's sites, presence of extra-intestinal disease and
      previous Crohn's proctitis to be related with problematic healing after a
      surgical repair. A positive relation was found between extra-intestinal disease
      and the number of repairs needed to ultimately obtain healing, whereas the
      relation with previous right hemicolectomy was negative. Multivariate analysis
      revealed the number of Crohn's sites as the only factor predicting problematic
      healing. A defunctioning stoma was not related to the healing rate and had its
      intrinsic morbidity with supplementary hospitalization (9.6 days). After a median
      follow-up of 40.4 (range 8-87) months, we observed 4 late recurrences in 25
      patients with healed RVF (16%). CONCLUSION: Closure of a RVF in Crohn's disease
      should not be considered an easy undertaking, especially in patients with several
      Crohn's sites. In this very heterogeneous group of patients the technique is
      adapted to the nature and the extent of accompanying anorectal disease.
      Construction of a temporary stoma is not mandatory and can be limited to complex
      cases. Healing can be obtained in 75% of all patients, although a late recurrence
      might occur.

PMID- 12790940
TI  - Results of anterior levatorplasty for rectocele.
AB  - OBJECTIVE: Transanal and transvaginal repair of rectocele have been advocated in
      the treatment of rectocele, with mixed results. The aim of this study was to
      assess our experience using anterior levatorplasty in the surgical management of
      rectocele. PATIENTS AND METHODS: Sixty of 90 women who had undergone anterior
      levatorplasty for rectocele over a seven year period were traced, and 44 (33 with
      rectocele only and 11 with rectocele and faecal incontinence) responded to a
      standardized questionnaire 6 months to 7 years (mean 3.5 years) after anterior
      levatorplasty. Results were expressed in general and specific improvement of
      symptoms and were classified as excellent, good, fair, or poor. The effects on
      social activities, sexual function, and employment were also assessed. RESULTS:
      General satisfaction with the operation was rated as good or excellent in 27 of
      33 (82%) and 18 of 24 (75%) patients with rectocele only at 2 and 3.2 years
      follow-up, respectively, and in 7 of 11 (64%) and 5 of 11 (45%) patients with
      rectocele and faecal incontinence at 2 and 4 years follow-up, respectively. 31
      (70%) and 34 (77%) of all patients reported an improvement in sensation and the
      ability to defaecate, respectively. An improvement in social activities, sexual
      satisfaction and employment was noted in 10 of 21 (48%), 10 of 23 (43%), and 7 of
      12 (58%) patients, respectively. CONCLUSION: Anterior levatorplasty provides good
      short and long-term symptomatic improvement in patients with rectocele and avoids
      complications associated with rectal or vaginal approaches.

PMID- 12790941
TI  - Quality of life of patients after surgical treatment of anal fistula; the role of
      anal manometry.
AB  - OBJECTIVE: This study was undertaken to assess the quality of life of patients
      after surgical treatment of anal fistula and to investigate whether anal
      manometry (AM) can guide the choice of the proper surgical intervention in these
      patients in order to protect the sphincter mechanism. PATIENTS AND METHODS: One
      hundred patients with anal fistula (AF) were studied prospectively (78 men; mean
      age 45 years; range 11-78). Cleveland Incontinence Score (CIS) was record pre
      operatively and 1 and 3 months postoperatively for each patient in order to
      specify their quality of life (QOL) before and after the surgical treatment.
      Also, anal manometry (AM) was performed pre-operatively and 1 month
      postoperatively. The pre-operative anal pressures and the type of fistula
      determined the kind of the surgical treatment. 55 patients had an
      intersphincteric fistula, 42 trans-sphincteric and 3 suprasphincteric. 65
      patients underwent laying open of the fistulous track, 7 fistulectomy and 28 were
      treated by seton fistulotomy. RESULTS: Three patients had defective gas control
      and 6 reported some degree of soiling. 3 patients developed recurrent fistula.
      CIS was significantly impaired (P=0.02) at the first postoperative month in these
      patients who were treated for trans-sphincteric fistula by fistulotomy; AM
      revealed significant decrease of anal pressures in these patients (resting and
      squeeze; P=0.007 and 0.0001 respectively); CIS and AM in the remaining cases
      revealed no significant deterioration of QOL and fall of anal pressures
      respectively. CIS was normal in the vast majority of patients at 3-months
      postoperatively. CONCLUSIONS: QOL of patients after surgical treatment of AF is
      unalterable on the understanding that the AF is simple and the treatment is not
      associated by incontinence or recurrence. Pre-operative AM is important regarding
      the choice of the proper surgical procedure.

PMID- 12790942
TI  - Assessment and classification of never operated and recurrent cryptoglandular
      fistulas-in-ano using hydrogen peroxide enhanced transanal ultrasound.
AB  - OBJECTIVE: Classification and visualization of fistula-in ano is used to
      determine surgical treatment according to the type of fistula, predict the
      recurrence rate and incontinence risk and compare the results of treatment
      published in literature. Hydrogen peroxide enhanced transanal ultrasound (HPUS)
      with the peroxide introduced through the external opening of the fistula gives a
      clear and accurate visualization of the track in relation to the sphincters. The
      aim of this study was to review never operated and recurrent cryptoglandular
      fistulas-in-ano visualized with the aid of HPUS in order to establish the
      anatomical differences. PATIENTS AND METHODS: Eighty-one patients with never
      operated (48) or recurrent (33) cryptoglandular fistulas-in-ano were assessed by
      clinical examination and HPUS. RESULTS: Never operated fistulas were single
      track, trans- or inter-sphincteric fistulas in 80%. In 15%, the tracks were sinus
      with no connection to the pectinate line. Two patients (5%) had a
      transsphincteric fistula with a ramification. No supra- or extra-sphincteric
      fistulas were found in the never operated fistula group. In the recurrent fistula
      patients, 57% had a single trans or intersphincteric track, 15% of the patients
      had a single track supra or extrasphincteric fistula and 27% had a ramified
      fistula. CONCLUSIONS: All never operated cryptoglandulair fistulas-in-ano were
      inter- or trans-sphincteric. An extra track was found in 5%. Recurrent fistulas
      in-ano were supra or extrasphincteric in 15% and ramified in 27%. Therefore,
      never operated fistula-in-ano does not require any special investigation before
      surgical treatment. However, before treating recurrent fistulas, visualization by
      HPUS is recommended to detect supra or extrasphincteric fistulas or ramification.

PMID- 12790943
TI  - Treatment of chronic pilonidal sinus with local anaesthesia: a randomized trial
      of closed compared with open technique.
AB  - OBJECTIVE: To compare open with closed treatment of chronic pilonidal sinus.
      PATIENTS AND METHODS: From 1993 to 1996, 100 patients were submitted to excision
      of chronic pilonidal sinus, with local anaesthesia and were randomized in two
      groups: group A in which open treatment and group B in which direct suture were
      performed. The follow-up, ranging from 37 to 89 months, was performed by
      outpatient visits or by phone. RESULTS: Short-term results showed 6 (12.0%) post
      operative complications in group A vs 10 (20.0%) in group B. Long-term results
      showed 9 (18.0%) complications in group A vs 7 (14.0%) in group B. Mean wound
      healing was 58 days (range: 29-93) in group A vs 12 (range: 9-61) in group B. The
      return to normal activity was 25.7 (range: 11-77) vs 10.4 (range: 5-32). Wound
      healing and the return to normal activity were the only statistically significant
      differences. CONCLUSIONS: Regarding morbidity neither technique has particular
      advantages over the other. The closed technique produced quicker wound healing
      and a quicker return to normal activity.

PMID- 12790947
TI  - Local staging of rectal cancer and planning management.

PMID- 12790948
TI  - Detection of lymph node metastases in colorectal carcinoma.
AB  - The detection of lymph node metastases is the single most important prognostic
      factor for patients with colorectal cancer. This review outlines the difficulties
      and methods of detecting positive lymph node metastases in this disease. An
      outline of traditional diagnostic methods including preoperative ultrasound and
      cross sectional imaging techniques are evaluated alongside newer modalities
      including immunoscintography and PET scanning and intraoperative radioguided
      imaging. Pathological methods of detecting positive nodal disease using standard
      histopathological staging, enhanced lymph node harvesting and determination of
      micrometastases are also discussed.

PMID- 12790949
TI  - Evaluation of the role of pre-operative magnetic resonance imaging in the
      management of rectal cancer.
AB  - OBJECTIVES: This study assesses the ability of body coil magnetic resonance
      imaging (MRI) to pre-operatively stage mural penetration, nodal status and
      circumferential resection margin (CRM) involvement of rectal cancer. PATIENTS AND
      METHODS: Between 1995 and 1997, MRI using a body coil was performed in
      consecutive patients with primary rectal carcinomas. Group A: 67 patients
      underwent surgery without long course neo-adjuvant therapy. Predicted tumour
      stage was compared to the histology of the specimen. Group B: 21 patients with
      MRI evidence of advanced disease, underwent long course neo-adjuvant therapy
      followed by repeat MRI prior to surgery. The second scan assessed response to
      treatment and likelihood of CRM involvement at subsequent surgery. RESULTS: Group
      A: Accuracy of pre-operative staging was: 'T' stage - 54%, 'N' stage - 77%,
      involvement of CRM by tumour - 97%. Group B: After long course neo-adjuvant
      therapy the second MRI scan was 95% accurate in predicting CRM involvement by
      tumour. CONCLUSION: In this study pre-operative rectal cancer staging with MRI
      and a body coil lacks accuracy in predicting mural penetration and nodal
      involvement. Body coil MRI can accurately predict the potential for CRM
      involvement. This technique may help determine which patients require long course
      neo-adjuvant therapy.

PMID- 12790950
TI  - Rectal excision with coloanal anastomosis for superficial distal third rectal
      cancer: survival and local recurrence.
AB  - OBJECTIVE: Appropriate surgical treatment of distal third rectal cancer limited
      to bowel wall (i.e. T1 or T2) in medically operable patients is controversial.
      Transanal excision can deprive some patients of accurate pathological staging,
      prognosis and cure. In contrast abdominoperineal resection has considerable
      practical and psychosocial problems largely related to a permanent colostomy. We
      hypothesize that superficial distal rectal tumours can be effectively treated
      with rectal excision and coloanal anastomosis. SUBJECTS AND METHODS: Prospective
      oncological study of 80 patients with distal third superficial rectal carcinomas
      treated by complete rectal excision with coloananl anastomosis from December 1977
      to January 1993 was carried out. The resected specimens were examined for depth
      of spread and number of histologically positive nodes. The actuarial local
      recurrence and survival rates for superficial node-negative and node-positive
      tumours were analysed independently. RESULTS: Seventy-eight patients had complete
      postoperative assessment. Thirty-one percent had received low-dose preoperative
      neo-adjuvant radiotherapy (3500 rads). Mean follow-up time in all patients was 70
      months on average. The lymph node involvement rate for T1 and T2 tumours was 12.5
      and 15.6%, respectively. The local recurrence rates for patients with (T1/T2) N0
      and (T1/T2) N1 were 1.5 and 16.7%, respectively, and the five year actuarial
      survival rates were 96.6 and 90%, respectively. The overall local recurrence was
      3.8% with five-year actuarial survival of 95.8%. CONCLUSIONS: Lymph node
      involvement in superficial tumours is not rare. Rectal excision with coloanal
      anastomosis results in a high cure rate especially for node-positive superficial
      tumours. This treatment strategy avoids the psychological trauma of colostomy
      following abdominoperineal resection and the potential risk of undertreatment by
      local excision.

PMID- 12790951
TI  - Screening of patients at high risk of colorectal cancer.
AB  - OBJECTIVE: To determine the present state of colonoscopic screening practice for
      patients at a high risk of developing colorectal cancer. METHODS: We assessed
      colonoscopic screening practice in nine colorectal surgery or gastroenterology
      units referring patients to the regional genetics centre in the North-west of
      England. The validity of the pedigree was confirmed by inspection of Hospital
      records, use of cancer registries and records of general practitioners across the
      United Kingdom. The screening activity at the participating centres was
      investigated by means of a questionnaire, site visit and study of case notes.
      RESULTS: One hundred and eight high risk families were identified. Outside the
      genetics unit, family history was not taken in a structured manner and family
      pedigree was not confirmed. In four units screening was offered directly by the
      consultant surgeon. Differing protocols for screening were in place in six units,
      but were frequently not adhered to. Colonoscopy completion rates were known in
      only four units (range 83-97%). Frequency of screening varied from 2 to 5 years.
      Recording of information was minimal outside the patients' records and there were
      no dedicated databases. Facilities for families to be screened together existed
      in three units and the psychological effect of screening was not determined
      outside the genetics centre. CONCLUSIONS: Screening practice should be
      standardized and specific criteria met before regular screening is initiated. A
      dedicated database should be established to record information from units
      screening patients at high risk of colorectal cancer.

PMID- 12790952
TI  - Curative resection for rectal carcinoma: definition influences outcome in terms
      of local recurrence.
AB  - OBJECTIVE: There are wide variations in local recurrence rate following curative
      surgery for rectal cancer and there are substantial inconsistencies among
      surgeons regarding the method of defining curative resection. This paper seeks to
      explore whether defining criteria is one of the important factors driving the
      variations in outcome. METHOD: A literature review was undertaken to find all UK
      based studies that had data on curative resection and local recurrence rates. The
      studies were divided into groups with distinct definitions of curative resection
      for rectal cancer. Meta-analyses were performed to pool the risks of local
      recurrence by group definition. Statistical tests were used to explore the
      variation in local recurrence by group. Confounding relationships of age, sex,
      Dukes stage, length of follow-up and year of study were explored as far as
      possible given the limitations of the available data. RESULTS: For rectal cancers
      significant differences were found between the pooled local recurrence risks by
      group definition (P < 0.01). Meta-regression tests including all the studies
      indicate that the definition of curative resection is an important predictor of
      local recurrence. CONCLUSION: It is suggested that a standardized approach
      towards defining curative resection and local recurrence may have a significant
      effect on outcomes in colorectal cancer surgery and would enable comparisons to
      be made between different series.

PMID- 12790953
TI  - Effect of age on the functional outcome of total abdominal colectomy for colonic
      inertia.
AB  - OBJECTIVE: Colonic inertia (CI) usually presents in women in the third decade of
      life; however, elderly patients are at times diagnosed with the disease. Total
      abdominal colectomy (TAC) is considered the preferred surgical treatment for
      patients with well established CI refractory to conservative and medical
      management. Surgeons are reluctant to proceed with colectomy in aged patients
      because of anticipated high morbidity and poor functional outcome. MATERIALS AND
      METHODS: We retrospectively reviewed the outcome in 14 patients over the age of
      65 years (range 65-80) (Group I) who underwent TAC for CI between 1988 and 1996.
      The functional and clinical outcome was compared with that of 41 patients under
      the age of 65 (range 21-61) (Group II) operated upon during the same time period.
      Functional outcome was assessed by postal and telephone questionnaires at least
      12 months following surgery. RESULTS: There was no major postoperative morbidity
      in either group. Three (21%) patients in Group I developed small bowel
      obstruction postoperatively and, of them, 2 required surgical treatment. In Group
      II the rate of obstruction was 7% (3 patients), with one patient requiring
      surgery. One patient in Group I subsequently underwent completion proctectomy and
      creation of an end ileostomy due to continued panenteric hypomotility. Three
      patients in Group I died during follow-up from causes unrelated to surgery. The
      mean frequency of spontaneous bowel movements following surgery was 3.8 (range 1
      10)/day in Group I and 2.9 (range 1-8)/day in Group II (P=NS). 'Excellent'
      outcome was reported by 7 patients (64%) in Group I and 39 patients (95%) in
      Group II (P=0.01). CONCLUSION: TAC can be performed in elderly patients with
      established CI with acceptable functional results and no increase in morbidity,
      resulting in lifestyle improvement. Complete physiological evaluation with
      increased emphasis on small bowel and gastric motility studies is required in
      this patient population.

PMID- 12790954
TI  - Anal plug for faecal incontinence.
AB  - OBJECTIVE: Despite the availability of pharmacological, behavioural and surgical
      treatments for faecal incontinence, many patients remain symptomatic. There are
      few devices designed specifically to cope with this, and perineal pads are
      inefficient and unacceptable for many patients. This study aimed to evaluate a
      new device in patients with intractable faecal incontinence. METHOD: Two sizes of
      a purpose-designed anal plug were evaluated in 20 patients with intractable
      faecal incontinence for solid or liquid stool. Each plug size was tested for 2
      weeks, with patients completing a structured questionnaire after each size.
      RESULTS: The majority [14/20] could not tolerate a plug due to discomfort. Four
      patients (20%) wished to continue to use a plug on a regular basis after the
      study, and two others on an occasional basis. However, for this minority who
      could tolerate a plug, it was highly successful at controlling faecal
      incontinence. There was no clear preference for the smaller or larger plug. There
      was no association between comfort in using the plug and anorectal sensitivity as
      measured by electrophysiological tests. It was not possible to predict which
      patients would benefit from plug use. CONCLUSION: The anal plug is effective in
      controlling faecal incontinence and is well tolerated in a minority of patients.
      Evaluation quickly reveals whether the patient will find it an effective and
      acceptable option. This device therefore offers a further management option for
      patients with faecal incontinence.

PMID- 12790955
TI  - A simplified defaecographic procedure for the assessment of faecal incontinence
      or obstructed defaecation.
AB  - OBJECTIVE: Various types of defaecography have been reported for research
      purposes. A simplified method for clinical use has not been devised for the
      assessment of disordered defaecation. The aim of this study was to describe a
      simplified procedure of defaecography and evaluate its usefulness in the
      diagnosis of faecal incontinence or obstructed defaecation. PATIENTS AND METHODS:
      Anorectal manometry and simplified defaecography were performed in 82 consecutive
      patients. The procedure of defaecography consisted of instillation into the
      rectum with a 100% weight per volume of barium in the sitting position through a
      Foley catheter with an inflated balloon, and several series of static radiograph
      at rest, during squeezing and straining according to deflation of the balloon.
      RESULTS: Positive rate of barium leakage after barium insertion was significantly
      higher in incontinent patients than constipated or asymptomatic patients (P <
      0.001, respectively). The degree of barium leakage was classified into mild in 18
      patients with faecal incontinence, moderate in 4 and severe in 2. Constipated
      patients had more difficulty trying to expel a catheter than incontinent or
      asymptomatic patients (P=0.001, P=0.03). Twenty-four percent of patients with
      obstructed defaecation could not expel the balloon and 48% could not evacuate
      barium sulphate completely. The positive rate of morphological changes such as
      rectocele, internal intussusception and band formation was higher in constipated
      patients than incontinent or asymptomatic patients (P=0.01, P=0.04). CONCLUSION:
      The grade of barium leakage or balloon prolapse reflected the severity of faecal
      incontinence. The ability in rectal emptying of the balloon or barium sulphate
      also correlated with the degree of outlet obstruction. The authors concluded that
      the present defaecographic technique was useful for the assessment of faecal
      incontinence or functional outlet obstruction, and recommend it due to its
      simplicity.

PMID- 12790956
TI  - Life table analysis of hernia following end colostomy construction.
AB  - OBJECTIVE: To study the long-term hernia rate and risk factors after end
      colostomy construction. PATIENTS AND METHODS: 86 patients with a permanent end
      colostomy constructed over 5 years were examined and interviewed. There were 35
      men and the mean age was 56.5 (28-87) years. Risk factors which were analysed
      included emergency operation, age over 60 years, obesity, steroids, cancer,
      infection at the stoma site, smoking and chronic obstructive airways disease.
      RESULTS: Para-colostomy hernia occurred in 12/86 cases (13.9%). The cumulative
      recurrence rose with duration of follow up. Overall 10/45 patients (22%) over 60
      years developed hernia vs. 2/41 patients (4.8%) less than 60 years (P=0.02).
      There were no other risk factors that correlated with para-colostomy hernia.
      CONCLUSIONS: These data indicate that the incidence of colostomy related hernia
      increases with follow up and is significantly higher in patients over the age of
      60. Other risk factors, particularly obesity and coexisting cardiorespiratory
      disease, have no impact.

PMID- 12790957
TI  - Bacterial translocation in a non-lethal rat model of peritonitis.
AB  - BACKGROUND: Bacterial translocation from the gut may occur under a variety of
      different clinical circumstances and has been implicated in the development of
      multiple organ failure. The aim of this study was to determine the distribution
      of bacterial translocation occurring in a model of chemically induced
      peritonitis. We also sought to document the degree of the associated immune and
      inflammatory response. METHODS: Though a midline laparotomy, rats were injected
      with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4,
      18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular
      influx, TNF-alpha and interleukin-6 concentrations and myeloperoxidase activity.
      Bacterial cultures were initiated from the free peritoneal fluid, mesenteric
      lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal
      mesothelial surface to determine its integrity. RESULTS: When comparing rats
      injected with zymosan with the controls, there was evidence of a peritoneal
      inflammatory response within 4 hours. Facultative gram negative bacteria were
      found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at
      48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h.
      No organisms were cultured from the liver, lung or kidneys. In addition there was
      a significant increase in intraperitoneal cell numbers (predominantly
      neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-alpha and IL
      6 concentrations (P < 0.05). There was extensive loss of the peritoneal
      mesothelial cells. The peritoneal inflammatory changes and bacterial
      translocation had resolved by 96 h. CONCLUSION: Bacterial translocation can be
      induced by the presence of an acute inflammatory focus in the peritoneal cavity.
      The translocation and inflammatory changes were associated with extensive loss of
      mesothelial cells. Nonetheless, these changes all resolved, indicating that the
      peritoneal cavity has a significant capacity to deal with such insults. A clearer
      understanding of the cellular and molecular events involved in the resolution
      phase could lead to improvements in the treatment of peritonitis.

PMID- 12790958
TI  - In vitro and preclinical studies of targeted alpha therapy (TAT) for colorectal
      cancer.
AB  - INTRODUCTION: Effective targeted cancer therapy requires high selectivity and
      cytotoxicity of the labelled product. We report the preparation and testing of
      anticolorectal cancer monoclonal antibody c30.6 radioimmunoconjugates (RIC)
      labelled with alpha-emitting Bismuth-213 and positron emitting Terbium-152 using
      two chelators, viz. Cyclic dianhydride of diethylenetriaminepentacetic acid
      (DTPA) and CHX-A" (a DTPA derivative). METHODS: Selectivity and stability of the
      RIC were tested in vitro (flow cytometry) and in vivo (biodistribution,
      organ/tumour uptake and retention). Cytotoxicity assays were carried out using
      tritiated thymidine uptake (inhibition of DNA synthesis) and MTS assay. RESULTS:
      High labelling efficiency (ranging between 89 and 91%) and stability over 2-5
      half-lives of the isotopes were seen. Kidney retention was not seen in contrast
      to high uptake and retention of both conjugates in tumours. Flow cytometry
      studies showed high specificity of the antibody before and after labelling and
      this unchanged targeting behaviour was reflected in cytotoxicity assays. These
      assays showed that only alpha-labelled antibody could selectively kill the cancer
      cells for activities as low as 2-3 microCi. The study also revealed that free
      isotopes or isotopes bound to nonspecific antibodies did not kill cancer cells.
      CONCLUSION: The stability of the RICs and outstanding cytotoxicity of the alpha
      emitter, together with no kidney retention and high tumour uptake and retention
      of the radiolabel, offers a new approach for the potential control of colorectal
      cancer.

PMID- 12790961
TI  - An old chestnut revisited.

PMID- 12790962
TI  - 5-amino-salicylate in the management of inflammatory bowel disease.
AB  - The role of aminosalicylates in the treatment of idiopathic bowel disease is
      reviewed, with emphasis on how the different formulations can be used in
      different clinical manifestations. Although not fully understood, the possible
      mechanisms of action of these agents are discussed and their adverse reactions
      noted. Their use in clinical practice, both in acute disease and in remission, is
      outlined with particular reference to the different delivery characteristics of
      the aminosalicylates, thus allowing their use according to the distribution of
      the disease. Finally, benefits that might come from maintenance therapy,
      including possible reduction in post-operative recurrence of Crohn's disease and
      the risk of colorectal cancer are mentioned.

PMID- 12790963
TI  - Patient quality of life after successful restorative proctocolectomy is normal.
AB  - OBJECTIVE: To measure quality of life (QoL), using validated health status
      instruments, of patients with functioning IPAA for CUC. PATIENTS AND METHODS:
      Between 1986 and 1997, a total of 77 patients had an IPAA. Thirteen patients were
      excluded [6 excised, 3 awaiting ileostomy closure, 2 lost to follow up, 2 serious
      unrelated illnesses]. Postal survey using SF36 and EuroQol questionnaires. Age,
      sex, year of pouch construction and stool frequency were documented. RESULTS:
      Fifty-six patients (87.5%) replied. Male:female ratio; 3:2. Median age; 34 years
      (range 13-64). Median time since pouch construction; 4 years (range 1-10 years).
      Median SF36 scores (range); physical function 86.6 (0-100), physical role 81.6 (0
      100), body pain 78.4 (22-100), general health 61.6 (5-100), vitality 57.6 (5
      100), social function 75.4 (25-100), emotional role 83.5 (0-100), mental health
      70.7 (16-100). All the SF36 scores were within the normal range, as were the
      EuroQol scores. Median EuroQol score (range); 0.85 (-0.07-1.0). Median EuroQol
      thermometer score (range); 83.3 (20-100). There was no correlation between
      objective QoL score and age, gender, stool frequency and year of pouch
      construction. CONCLUSION: The QoL for patients with a functioning IPAA for CUC
      measured using validated health status instruments is normal. Age, gender, stool
      frequency and year of construction do not affect QoL outcome after the IPAA for
      ulcerative colitis.

PMID- 12790964
TI  - A prospective randomized trial of consultant-led injection sclerotherapy compared
      with nurse practitioner-led noninvasive interventions in the management of
      patients with first and second degree haemorrhoids.
AB  - OBJECTIVE: To determine whether nurse practitioner (NP)-led advice in relation to
      bowel and defecatory habits in hemorrhoidal disease is as effective as local
      invasive treatment (sclerotherapy) in the management of patients with symptomatic
      1st and 2nd degree haemorrhoids, with respect to both alleviation of presenting
      symptoms and relapse rate, and patients' understanding of their condition.
      PATIENTS AND METHODS: In a prospective randomized trial, 25 patients with
      bleeding haemorrhoids were allocated to receive either standard medical injection
      sclerotherapy (Group 1, n=13) or NP-led advice, information and bowel habit
      retraining (Group 2, n=12). Bulking agents were offered, when deemed appropriate,
      to patients in both groups. Treatment was administered by two clinicians only.
      Patients were assessed at 8 weeks, 4 months and finally at 6 months post
      treatment and any symptoms present were graded. RESULTS: At 6 months, symptomatic
      improvement was similar in both groups (mean range 3 points) with a patient
      expected to get better with a good degree of confidence (C.I: 2-4 points).
      However those patients in Group 2 would be expected to have a slightly better
      minimum level of improvement (GP 1 P=0.004 GP 2 P=0.0005). At six months, there
      was no statistical difference between the two groups with regard to the patient's
      perception of the amount of information given, the clarity of the explanation,
      and the ability of the patient to understand and discuss their problem. In
      relation to understanding the cause of their problem patients in Group 2 felt
      they had a higher level of understanding of the cause of their problem (U=13,
      NA=7, NB=10, P=0.05) and felt more able to prevent their problem returning (U=12,
      NA=7, NB=10, P=0.05). CONCLUSION: A bulking agent and Nurse led education, advice
      and bowel habit retraining is as effective in reducing the incidence of bleeding
      from 1st and 2nd degree haemorrhoids as injection sclerotherapy. Patients who
      consult a NP with symptomatic 1st and 2nd degree haemorrhoids feel more empowered
      in the long term. Non-invasive bowel retraining methods should be offered as an
      alternative to more traditional, invasive treatments for patients with
      symptomatic early hemorrhoidal disease.

PMID- 12790965
TI  - Long-term results of faecal diversion for refractory perianal Crohn's disease.
AB  - BACKGROUND AND AIMS: Faecal diversion (FD) for refractory anoperineal Crohn's
      disease (APCD) is thought to be unsatisfactory with a low overall rate of
      defunctioning stoma closure. However, only a few patients have so far been
      reported in the literature. The aim of this study was to reassess the long-term
      efficiency of FD for APCD. METHODS: Among 136 patients who were operated for APCD
      over a 18-year period, 17 underwent FD. The factors assessed were the mortality
      and morbidity of stoma formation, the evolution of anoperineal Crohn's disease
      after FD, and predictive factors of FD effectiveness. RESULTS: Mean follow-up
      after FD was 135 +/- 79 months (range 20-328). Initial healing of APCD was
      observed in 11 patients (65%), allowing stoma closure after 14 +/- 9 months
      (range 3-52). The 6 other patients underwent abdominoperineal resection (APR) for
      persistent APCD. Three of the 11 patients with normal bowel continuity underwent
      secondary APR for APCD recurrence. Thus, at the end of follow up 9 (53%) patients
      had definitive end ileostomy and 8 (47%) continued to have normal bowel
      continuity with a mean follow up of 124 +/- 90 months (range 12-292) after stoma
      closure. The presence of rectal lesions at the time of FD was the only predictive
      factor of poor outcome: 8/9 (89%) patients with rectal lesions underwent APR vs
      1/8 (13%) patients without rectal lesion (P < 0.01). CONCLUSIONS: Faecal
      diversion for anoperineal Crohn's disease produced a high initial rate of
      anoperineal lesion healing. After long-term follow-up, results of faecal
      diversion are good (normal bowel continuity was restored in 89%) in patients
      without associated rectal lesions. However, in patients with associated rectal
      lesions, the prospects for restoring continuity were limited, thus making faecal
      diversion a questionable procedure.

PMID- 12790966
TI  - Peri-operative management of patients having external anal sphincter repairs:
      temporary prevention of defaecation does not improve outcomes.
AB  - OBJECTIVE: To determine whether there was any detectable difference in outcomes
      of external anal sphincter repair depending on whether patients were managed
      routinely with a covering stoma, a constipating dietary regimen or a laxative
      dietary regimen in the early postoperative period. PATIENTS AND METHODS: A
      consecutive retrospective series of 299 anal sphincter repairs undertaken on 286
      patients within a single institution was studied. Patients were divided into
      three groups depending on the peri-operative regimen followed: routine use of a
      covering stoma (group 1), routine use of a postoperative constipating dietary
      regimen (group 2) and routine use of a laxative dietary regimen (group 3). Choice
      of peri-operative regimen depended on surgeon preference alone. Short-term
      outcomes (length of stay, complications) and long-term outcomes (functional
      reported degree of continence, anal ultrasound and physiology test results) were
      assessed in relation to peri-operative group as well as aetiology of sphincter
      damage. RESULTS: Short-term results (complications of surgery) were obtainable in
      all patients; long-term results were available for 89% of patients. Length of
      stay was similar for all 3 groups (excluding re-admission for stoma closure).
      Complication rates were not significantly different between the three groups.
      Functional improvement in continence was reported by 68% of group 1, 69% of group
      2 and 79% of group 3 (differences not statistically significant). An anatomical
      sphincter defect was detected postoperatively in 8% of patients in group 1, 9% in
      group 2 and 7% of group 3. Poorer outcomes were achieved in older patients and in
      patients with previous ileo-anal pouch formation. Early faecal impaction and
      repair breakdown were independently associated with poor long-term outcomes.
      CONCLUSIONS: Neither routine use of a covering stoma nor a postoperative
      constipating regimen produced better results following external anal sphincter
      repair than did the use of a postoperative laxative regimen which encouraged
      early passage of loose stool without the need for straining.

PMID- 12790967
TI  - Administration of Lactobacillus plantarum 299v reduces side-effects of external
      radiation on colon anastomotic healing in an experimental model.
AB  - OBJECTIVE: Preoperative radiotherapy of patients with rectal carcinoma is
      frequently used to reduce the incidence of local recurrence. However, the
      radiation therapy is associated with several complications, including diarrhea,
      retarded anastomotic healing and mucosal atrophy. Exogenous administration of
      lactobacilli has been demonstrated to be effective in stimulating intestinal
      mucosal growth and reduce mucosal inflammation. The objective of this study was
      to examine the effects of Lactobacillus plantarum 299v administration on external
      radiation injury in colon anastomotic healing at different time points. MATERIAL
      AND METHODS: Sprague-Dawley rats were treated with Lb. plantarum 299v or saline
      as control and received external radiation of the lower abdomen (10 Gy/day) on
      day 3 and 7 of the experiment. After 4 days, a colonic resection with anastomosis
      was performed. Animals were sacrificed on 4th, 7th and 11th day postoperatively.
      Body weight, white blood cell (WBC) count, mucosal myeloperoxidase (MPO)
      activity, hydroxyproline, nucleotide, DNA and RNA content, colonic bacterial
      microflora, bacterial translocation and histology were evaluated. RESULTS: On the
      4th postoperative day body weight, WBC and MPO decreased significantly after
      radiation. On the 7th postoperative day MPO decreased after radiation. In the two
      irradiated groups it decreased significantly in the Lb. plantarum group compared
      to the radiated group without treatment. Collagen concentration on the 7th
      postoperative day was significantly higher in Lb. plantarum group without
      radiation compared to the group with radiation without Lb. plantarum. On the 11th
      postoperative day MPO was significantly higher in irradiated rats without
      treatment compared to Lb. plantarum treatment. The collagen concentration
      increased significantly in the irradiated Lb. plantarum group compared to the
      other two groups. CONCLUSION: The collagen content decreased and MPO activity
      increased significantly of the colonic anastomosis in irradiated rats without
      treatment compared to those treated with Lb. plantarum. It therefore seems that
      administration of Lactobacillus plantarum 299v reduces the intestinal injury and
      inflammation following external radiation and improves the colonic anastomotic
      healing.

PMID- 12790968
TI  - Long-term outcome after colectomy in severe idiopathic constipation.
AB  - OBJECTIVE: The specific aim of the investigation was to assess the long-term
      results of subtotal colectomy with ileorectal anastomosis in patients with severe
      idiopathic constipation. PATIENTS AND METHODS: 40 patients with severe idiopathic
      constipation were operated on between 1981 and 1993. Patients were accepted for a
      colectomy and an ileo-rectal anatomosis after a thorough gastro-intestinal
      investigation. Pre-operative bowel frequency was less than 2 movements per week,
      and slow transit was documented. Postoperative complications occurred in eight
      patients. Early re-operation was performed in 2 patients for small bowel
      obstruction. RESULTS: Mean follow-up was 11 (range 5-16) years. The defaecation
      frequency at follow-up was 3.0 +/- 1.9 per day. Twenty-nine patients stated that
      they were satisfied and 11 were dissatisfied with the procedure. The outcome did
      not correlate with observed signs of outlet obstruction, blunted rectal sensation
      or presence of a psychiatric diagnosis. At 5-16 years after the procedure 33
      patients still retain the ileo-rectal anastomosis. Seven patients have had
      further procedures: Five patients have an ileo-anal pouch, one has a continent
      ileostomy and one has a conventional ileostomy. Small bowel obstruction was
      encountered in 17 patients, in 10 of these surgical treatment was necessary.
      CONCLUSION: It is concluded that colectomy and ileorectal anastomosis for the
      treatment of severe idiopathic constipation causes an increase in the number of
      bowel motions, but is deemed successful only by 3 out of 4 patients. Secondary
      morbidity is considerable.

PMID- 12790969
TI  - The dose response of the internal anal sphincter to topical application of
      glyceryl trinitrate ointment.
AB  - INTRODUCTION: Glyceryl trinitrate (GTN) ointment has been used for the treatment
      of chronic anal fissure based on the assumed pathophysiology that the fissure is
      due to internal anal sphincter hypertonia and that GTN causes relaxation. METHOD:
      48 patients, with a diagnosis of haemorrhoids, underwent 24 h anal manometry
      following application of different concentrations (placebo, 0.1%, 0.2%, 0.4%) of
      GTN ointment. RESULTS: We have found that there was a progressive relaxation with
      increasing doses (placebo -8.8%, 0.1% GTN -21.9%, 0.2% GTN -27.2%, 0.4% GTN 
      33.1%). One way ANOVA showed this progression was significant (P=0.020), with the
      difference lying between placebo and 0.4% GTN (Tukey multiple comparisons,
      P=0.017). Only 3 patients experienced headaches and these were split evenly
      between the treatment arms. CONCLUSION: The internal anal sphincter has a dose
      related response to GTN and when dose application is strictly applied higher
      doses may be used without an increase in side-effects.

PMID- 12790970
TI  - Non-specific colitis, is it a justifiable diagnosis?
AB  - OBJECTIVE: The terms non-specific and chronic colitis are often used by
      histopathologists. The aim of this study is to look into the validity of the
      label non-specific chronic colitis (NSCC), the consistency of its reporting, as
      well as its clinical usefulness in patients who, on review, have shown to have
      normal biopsies. METHODS: Colonic and rectal biopsies from 35 patients who
      presented with acute onset diarrhoea, were initially diagnosed as nonspecific
      chronic colitis (NSCC) by a number of pathologists in one Department, and were
      reviewed by an outside pathologist (NYH) without the knowledge of the clinical
      details. A previously described set of histological criteria in reporting colonic
      biopsies in inflammatory conditions were used. RESULTS: Normal biopsies were
      found in 13 of the 35 patients (37%). These patients recovered without clinical
      intervention. In a further seven patients there was active inflammation with no
      features of chronicity, in 12 patients there were features of chronicity, in two
      patients there were hyperplastic polyps, and in one patient there were features
      of solitary ulcer syndrome. CONCLUSION: NSCC was used, without consistency, to
      cover a variety of conditions, including normal biopsies, sometimes relaying a
      wrong message. We suggest that histological criteria for chronicity should be
      adhered to when this label is used and the term Non-Specific Colitis should no
      longer be used.

PMID- 12790971
TI  - Sulindac and tamoxifen in the treatment of desmoid tumours in patients with
      familial adenomatous polyposis.

PMID- 12790972
TI  - Ensuring the optimum anastomotic level in restorative proctocolectomy.

PMID- 12790973
TI  - Does trephine colostomy produce a satisfactory stoma?

PMID- 12790974
TI  - Consensus statement of definitions for anorectal physiology and rectal cancer.

PMID- 12790975
TI  - ACPGBI annual meeting.

PMID- 12790979
TI  - Colitis indeterminate.

PMID- 12790976
TI  - Resources for coloproctology.

PMID- 12790980
TI  - Diverticular colitis: diagnosis and management.
AB  - Diverticular colitis is a recently recognized nosological entity in which a
      chronic focal mucosal sigmoid colitis occurs in association with diverticulosis.
      It usually presents with rectal bleeding and may be difficult to distinguish
      clinically, endoscopically and pathologically from other segmental colitides
      including ulcerative, Crohn's, ischaemic, infective and NSAID-induced colitis as
      well as diverticulitis. Uncontrolled data suggests that most patients respond
      satisfactorily to treatment with a high fibre diet, antibiotics and/or
      aminosalicylates, but a minority with persistent or recurrent symptoms require
      sigmoid resection. This paper reviews the literature on diverticular colitis and
      concludes with an algorithm suggesting the optimal management of patients who
      present with rectal bleeding in association with segmental sigmoid colitis and
      diverticulosis.

PMID- 12790981
TI  - Locoregional recurrence in patients with anastomotic leakage after anterior
      resection for rectal carcinoma.
AB  - OBJECTIVE: Anastomotic leakage is a serious complication after anterior resection
      for rectal carcinoma. It is controversial whether anastomotic leakage influences
      the rate of locoregional recurrence and therefore survival. PATIENTS AND METHODS:
      The data of 940 patients with invasive rectal carcinoma stage I-III treated by
      curative anterior resection from 1978 to 1996 at the Department of Surgery of the
      University of Erlangen were analysed. Patients who received neoadjuvant or
      adjuvant treatment were excluded as well as patients who died postoperatively. 89
      out of 814 patients (10.9%) developed an anastomotic leakage after anterior
      resection. RESULTS: The rate of locoregional recurrence during the first five
      postoperative years of all patients was 13.6%. In patients with anastomotic
      leakage the rate of locoregional recurrence was 22.0%, significantly higher than
      in patients without anastomotic leakage which was 12.5%, (P=0.018). On
      multivariate Cox regression analysis anastomotic leakage was shown to be an
      independent risk factor for locoregional recurrence (relative risk: 1.7, CI 95%:
      1.02-2.75, P=0.042). Also cancer-related survival was influenced significantly by
      anastomotic leakage in univariate analysis as well as in multivariate analysis
      (relative risk: 1.6, CI 95%: 1.1-2.2, P=0.017). CONCLUSION: Anastomotic leakage
      after anterior resection for rectal carcinoma is a risk factor for locoregional
      recurrence and decreases cancer-related survival.

PMID- 12790982
TI  - Comparison of the Moskowitz criteria and the pouchitis disease activity index
      (PDAI) for diagnosis of ileoanal pouch inflammation.
AB  - OBJECTIVE: To prospectively compare two indices for diagnosis of pouchitis:
      Moskowitz criteria and pouchitis disease activity index (PDAI). PATIENTS AND
      METHODS: Fifty-six consecutive patients with an ileoanal pouch for ulcerative
      colitis were recruited. A clinical questionnaire was composed and the Oresland
      functional score calculated. Pouchoscopy and biopsy were performed after
      cleansing of the pouch. RESULTS: Seven patients had pouchitis according to both
      Moskowitz and PDAI ('positive' group). Five patients had PDAI > or = 7, but did
      not fulfil the Moskowitz criteria ('negative' group). The pouchoscopy and
      Oresland functional scores were similar between the two groups. The biopsy
      neutrophilia and ulceration were more prominent in the 'positive' group
      (chi2=5.18, P < 0.05), whereas urgency (chi2=8.4, P < 0.001), evacuation
      difficulties (chi2=5.18, P < 0.05) and history of bleeding per pouch (chi2=4.18,
      P < 0.05) were more pronounced in the 'negative' group. CONCLUSION: Moskowitz
      criteria may be broadly in agreement with the PDAI; these, however, cannot be
      regarded as interchangeable.

PMID- 12790983
TI  - A double-blind randomized placebo-controlled trial of oral indoramin to treat
      chronic anal fissure.
AB  - BACKGROUND: Indoramin is an alpha1-adrenoceptor antagonist and has been shown to
      reduce anal resting pressure. Its therapeutic potential has not been explored.
      The aim of this study was to determine the outcome of treatment with oral
      indoramin on patients with chronic anal fissure in the setting of a double-blind
      randomized placebo-controlled trial. METHODS: Twenty-three patients with chronic
      anal fissure were computer randomized to receive a 6-week course of oral
      indoramin (20 mg) or placebo in identical capsules, twice daily and with bulk
      forming laxatives. Pain was assessed by a visual analogue scale from 0 to 10.
      Anal resting pressure, heart rate and blood pressure were recorded. Patients were
      reviewed 1 h after taking the capsule and at 2, 6 and 12 weeks thereafter.
      RESULTS: Fourteen patients were randomized to indoramin and 9 to placebo. Maximum
      anal resting pressure was reduced from a mean of 96.4 cm H2O (+/- 32) to 67.6 cm
      H2O (+/- 26), 1 h after indoramin (P=0.02) and there was no significant change
      after placebo. There were no significant changes in heart rate or blood pressure.
      Pain was reduced in the placebo group from a score of 4.9 to 2.0 after 6 weeks (P
      < 0.01) but not in the indoramin group. After 6 weeks, healing had occurred in
      one (7%) patient in the indoramin group and in 2 (22%) in the placebo group (P >
      0.1). After 3 months, the chronic anal fissure in the indoramin group had
      recurred. The trial was terminated early because of poor healing rates.
      CONCLUSION: An oral dose of indoramin (20 mg) administered twice daily reduced
      anal resting pressure by 30% compared with pretreatment levels but was
      ineffective in healing chronic anal fissures.

PMID- 12790984
TI  - Multiplanar anal endosonography--normal anal canal anatomy.
AB  - INTRODUCTION: Volume acquisition during anal ultrasound enables multiplanar
      imaging of the anal canal. The normal ultrasonic multiplanar appearance of the
      anal canal is described and gender differences in canal anatomy are highlighted.
      METHODS: Ten male and 12 female normal volunteers (mean ages 31.5 years (s.d.
      5.9) and 31.2 (s.d. 6.7)) had three-dimensional anal endosonography (3-D AES).
      Each volume dataset was seeded in the axial plane facilitating multiplanar
      identification of known anatomical structures. RESULTS: The anterior external
      anal sphincter (EAS) was significantly longer in men than women 30.1 mm (3.9) vs
      16.9 mm (7.4) (P < 0.001). There was no difference in the length of the
      puborectalis 24.7 mm (6.4) vs 24 mm (5) (P=0.78) in men compared with women. The
      cranial extent of the anterior EAS was tilted forward in both sexes. The angle
      formed by the anterior EAS and the longitudinal axis of the anal canal was more
      acute in men than in women (11.1 degrees vs 18.6 degrees; P=0.007). Dataset
      volume seeding of familiar structures in the axial plane allowed the multiplanar
      endosonographic anatomy to be described. CONCLUSIONS: Multiplanar AES has enabled
      detailed longitudinal measurement of the components of the anal canal and has
      revealed important gender differences. The multiplanar ultrasonic appearance of
      the normal anal canal has been described for the first time.

PMID- 12790985
TI  - Stapled mucosectomy for acute thrombosed circumferentially prolapsed piles: a
      prospective randomized comparison with conventional haemorrhoidectomy.
AB  - OBJECTIVE: Stapled mucosectomy has been developed as an alternative to
      conventional haemorrhoidectomy for the elective treatment of haemorrhoids, but
      has not been assessed in the emergency setting. The aim of this study was to
      compare this technique with a conventional procedure for acute thrombosed
      circumferential prolapsed haemorrhoids. PATIENTS AND METHODS: A prospective
      randomized comparison of conventional Milligan-Morgan haemorrhoidectomy and
      stapled mucosectomy was carried out on 35 consecutive patients presenting with
      acute thrombosed circumferential prolapsed haemorrhoids. Operative data,
      postoperative stay, pain assessment and persistent symptoms were compared at
      discharge and at 2 week and 6 week review. Additionally at 6 week review the time
      to return to work was recorded and an endoanal ultrasound was carried out.
      RESULTS: Thirty patients were randomized and followed up for six weeks. Although
      postoperative stay and in-hospital analgesia were the same, patients from the
      stapled group reported significantly more pain at discharge. However, by 2 weeks
      the conventional group reported significantly higher pain scores particularly on
      passing stool. By this stage over half the stapled group patients reported no
      pain at all. More patients in the conventional group complained of persistent
      symptoms of pain, bleeding and discharge at 2 week and 6 week review with 20%
      requiring readmission compared with none in the stapled group. The median return
      to work was significantly shorter for the stapled group (14 days vs 28 days, P <
      0.05). Although all patients claimed to be continent, two patients from each
      group had ultrasonic evidence of internal sphincter damage. CONCLUSION: Stapled
      mucosectomy for acute thrombosed circumferential piles is feasible and may result
      in less pain, a more rapid resolution of symptoms and an earlier return to work
      compared with a conventional procedure.

PMID- 12790986
TI  - Impact of surgeon organization and specialization in rectal cancer outcome.
AB  - PURPOSE: The present study was designed to assess the differences in the outcome
      of patients with rectal cancer treated by a group of surgeons before and after
      being organized as a Coloproctology Unit at the same University Department of
      Surgery. METHODS: Comparison of two periods of rectal cancer surgery: I (1986-91)
      and II (1992-95). Period I: 94 patients were operated on by 14 general surgeons.
      Period II: 108 patients were operated on by only 4 surgeons of the same group
      organized as a Colorectal Surgery Unit after visiting referral centres abroad,
      adopting techniques such as total mesorectal excision (TME) for middle and low
      rectal cancer and washout of rectal stump. Mean follow-up during periods I and II
      was 69.1 and 42.0 months, respectively. A prospective data base analysis was
      used. Survival and local recurrence rates were calculated by the actuarial
      method. For comparison between groups the log rank method was used. RESULTS: The
      two groups were comparable with respect to mean age, gender, TNM and rectal
      tumour location. A significant increase in radical resectability and a decrease
      of the Abdominoperineal resection (APR)/Low anterior resection (LAR) ratio were
      observed in the second period. The overall pelvic recurrence rate was 25% in the
      first period and 11 in the second (P < 0.01). Significant differences were also
      found when the patients with LAR were compared between both periods, 30% vs 9% (P
      < 0.01) and specially when the 10 cm anal verge distance was considered to divide
      the LAR groups. No differences were found regarding the APR procedures in both
      periods. There was improved cancer-specific survival for the LAR group in the
      second period (P=0.03). CONCLUSION: Specialization and centralization influence
      the quality of rectal cancer surgery, mainly local recurrence rates and survival
      after low anterior resection.

PMID- 12790987
TI  - Does anorectal manometry predict clinical outcome after laparoscopic ACE
      procedures in children with spina bifida?
AB  - PURPOSE: The laparoscopic antegrade continence enema (LACE) procedure is used for
      the treatment of faecal incontinence in children with spina bifida. The purpose
      of this study was to relate the outcome of the LACE procedure to anorectal
      function, as determined by anorectal manometry. METHOD: Eleven children with
      spina bifida who had the LACE procedure underwent anorectal manometry (ARM) to
      document their anorectal function, and its relationship to the level of
      continence obtained following surgery. RESULTS: There was a consistently high
      level of functional continence achieved following surgery despite wide
      variability in the parameters of anorectal manometry. There was no demonstrable
      correlation between the outcome of the LACE procedure and anorectal function as
      assessed by manometry. CONCLUSION: Anorectal function as determined by manometry
      failed to predict outcome after the laparoscopic ACE procedure in children with
      spina bifida.

PMID- 12790988
TI  - Endoanal ultrasound or magnetic resonance imaging for preoperative assessment of
      anal fistula: a comparative study.
AB  - OBJECTIVE: To compare endoanal ultrasound (EUS) with a 10-MHz probe vs. bodycoil
      magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula.
      SUBJECTS AND METHODS: 23 patients with fistula in the anal region underwent
      preoperative 0.5 T bodycoil MRI and 10 MHz EUS which included probing in 6
      patients. The results of the EUS and MRI were compared against the surgical
      findings as a reference method. RESULTS: In classification of the primary tract
      there was agreement between EUS and surgical findings in 14 (61%) and between MRI
      and surgery in 11 (48%). Concerning the presence of an internal opening the
      corresponding figures were 17 (74%) and 10 (43%) and in judging the presence of
      an extension or an abscess 15 (65%) vs. 11 (48%), respectively. In three out of
      eight patients with nonhealing or recurrence after surgery preoperative imaging
      had shown an extension and/or an abscess that was not identified by the surgeon.
      CONCLUSION: EUS, sometimes complemented with probing, is well comparable to
      bodycoil MRI in classifying and describing the topography of an anal fistula.

PMID- 12790989
TI  - Is routine histological reporting of doughnuts justified after anterior resection
      for colorectal cancer?
AB  - OBJECTIVE: 'Doughnuts' of colonic tissue which remain on a circular stapler after
      firing are routinely examined histologically. However, Royal College of
      Pathologists' guidelines state that this is not necessary. The aim of this study
      was to examine current practice among pathologists in one region in the UK and to
      determine the incidence of clinically significant pathology within colonic
      doughnuts. METHODS: Current practice in all pathology Departments within the
      South-west Region was examined and 100 doughnuts from anterior resection
      specimens were reviewed for the presence of abnormal pathology. RESULTS: Practice
      varied between hospitals with only 15% following guidelines for examination of
      doughnuts and 38% following guidelines for reporting of resection margins. Review
      of pathology specimens demonstrated no incidence of colonic adenocarcinoma in a
      doughnut. Benign pathology was present in 9% and dysplasia in 3% but in no case
      was patient management altered as a result of the pathology report. CONCLUSION:
      Application of recommended guidelines is inconsistent. We have demonstrated a low
      incidence of clinically significant pathology in doughnuts and more economical
      guidelines could therefore be safely applied without detriment to patient care.

PMID- 12790991
TI  - Pile banding in anti coagulated patients.

PMID- 12790990
TI  - Primary adenosquamous carcinoma of the rectum. Report of 4 cases and review of
      the literature.
AB  - OBJECTIVE: To review the experience of two referral centres in the management of
      an infrequent condition: primary adenosquamous carcinoma of the rectum, a rare
      disease. MATERIALS AND METHODS: Four cases of primary adenosquamous carcinomas of
      the rectum are reported with a review of the literature. No preoperative
      diagnosis of adenosquamous carcinoma was established. All tumours were located in
      the rectum. Two patients presented with liver metastasis. No preoperative
      therapies were indicated. All patients underwent surgery. RESULTS: Patients
      underwent anterior resections (n=2), recto-sigmoid resection (n=1) and abdomino
      perineal excision (n=1). All resected specimens had positive lymph nodes and
      metastatic liver disease was confirmed in the two cases. No adjuvant therapy was
      carried out after surgery and patients died within 8 months after surgical
      treatment. CONCLUSIONS: Adenosquamous carcinoma of the rectum is a rare and
      aggressive tumour characterized by coexisting of malignant glandular and squamous
      components. Presentation is usually at an advanced stage. The tumour is
      aggressive and metastatic disease at the time of diagnosis is common. Surgery is
      the treatment of choice. Adjuvant therapy is difficult to evaluate prospectively
      due to the rarity of the condition. Survival is less than 50% than that for
      adenocarcinoma.

PMID- 12790992
TI  - Percutaneous endoscopic colostomy: an alternative treatment of acute colonic
      pseudo-obstruction.

PMID- 12790993
TI  - Local methods of treatment of rectal cancer.

PMID- 12790995
TI  - European Association of Coloproctology. First annual meeting, 15th-16th
      September, Versailles, France.

PMID- 12790998
TI  - Surgical treatment of ulcerative colitis.

PMID- 12790999
TI  - Anorectal manifestations of sexually transmitted infections.
AB  - Sexually transmitted infections have a wide range of clinical presentations,
      including involvement of the anal verge, anal canal and rectum. This review
      focuses on anorectal sexually transmitted infections which may cause diagnostic
      difficulty when encountered by the coloproctologist. An approach to the diagnosis
      of a variety of sexually transmitted infections is set out, with a discussion of
      the role of biopsy and a summary of relevant histopathological findings. The
      value of early antibiotic treatment is discussed. Problems related to HIV/AIDS
      are highlighted, as clinical presentation may be atypical in immunosuppressed
      individuals. Sexually transmitted oncogenic viruses and their role in anal
      neoplasia are also briefly summarized.

PMID- 12791000
TI  - The ileo neorectal anastomosis: an experimental study on development of the
      surgical technique and theoretical background.
AB  - OBJECTIVE: The keystones of surgical treatment of ulcerative colitis and familial
      adenomatous polyposis are resection of the diseased colon with either an
      ileostomy or restoration of oro-anal continuity with an ileo-anal pouch. The ileo
      pouch anal anastomosis however, has a 15-35% pouch-related complication rate, 10%
      failure rate and is accompanied by an unpredictable functional outcome. In order
      to reduce these unfavourable rates and to improve functional results an
      alternative surgical technique, the ileo neorectal anastomosis (INRA), was
      developed experimentally. MATERIALS AND METHODS: In an experimental study 12
      Yorkshire-Dutch landpigs had a subtotal colectomy and rectal mucosectomy.
      Subsequently a vascularized ileal mucosa sling was created and transposed on to
      the denuded rectal muscular cuff in eight. In another four animals a non
      vascularized mucosa sling was transposed. The covering ileostomy was closed after
      3 weeks. Repeated endoscopies, histological examinations of mucosal biopsies and
      rectal compliance measurements were carried out to evaluate the functional result
      of the neorectum. RESULTS: The surgical procedure of the INRA was technically
      successful in this animal study. Repeated endoscopy and histology showed complete
      ileal mucosa ingrowth in the neorectum without severe fibrosis in the group of
      animals with a vascularized sling. At follow up after 1 year no colonic
      metaplasia had occurred. Measurements of the neorectal reservoirs in the group of
      animals with a vascularized INRA procedure showed a median 'maximum tolerated
      volume' of 338 ml (range 300-410 ml). CONCLUSION: The INRA is technically
      feasible and reproducible. The histologically proven survival of the vascularized
      ileal mucosa and development of a compliant neorectal reservoir make the INRA an
      interesting alternative restorative procedure. Avoidance of the pouch-related
      complications of the ileo pouch anal anastomosis by this procedure might herald a
      new era of restorative surgery.

PMID- 12791001
TI  - A comparison of the effect of loperamide in oral or suppository form vs placebo
      in patients with ileo-anal pouches.
AB  - OBJECTIVE: The effect of the anti-diarrhoeal drug, loperamide hydrochloride, on
      bowel function in patients with an ileo-anal pouch was studied by means of a
      blinded, three-tailed, case-controlled and randomized crossover trial, using a
      daily dose of 12 mg in either oral (4 mg t.d.s.) or suppository (6 mg b.d.) form.
      PATIENTS AND METHODS: Daily stool frequency was recorded in a diary and an
      objective measure of pouch motor function was obtained at the end of each
      treatment phase. Ten subjects (seven males, three females) aged 23-50 years
      (median 38 years) were studied 9-48 months (median 27 months) after ileostomy
      closure. Eight pouches had been constructed for ulcerative colitis and two for
      familial adenomatous polyposis (9J, 1W). RESULTS: Mean daily stool frequency
      during the oral loperamide phase was lower than during both the placebo (P=0.05)
      and suppository (P < 0.02) phases. Stool frequency did not differ significantly
      between placebo and suppository phases. There was a strong inverse correlation
      between mean daily stool frequency and pouch capacity (r=-0.82 after both oral
      and suppository phases). Large isolated pouch contractions were evident in five
      of eight subjects studied; suppression was observed in two of the five after oral
      loperamide and in three of the five after loperamide suppositories. Rhythmic
      pouch contractions were seen in four subjects and suppression was evident after
      loperamide suppositories (but not after oral loperamide) in three. A daily oral
      dose of 12 mg loperamide significantly lowered stool frequency in pouch patients
      and modified some aspects of pouch contraction. Loperamide suppositories produced
      more prominent suppression of pouch contractions but did not lower stool
      frequency. CONCLUSION: This suggests that the beneficial effect of oral
      loperamide is primarily due to its action on intestine proximal to the pouch
      itself.

PMID- 12791002
TI  - A multivariate analysis of risk factors associated with recurrence following
      surgery for Crohn's disease.
AB  - OBJECTIVE: The aim of this study was to identify risk factors associated with the
      recurrence of Crohn's disease (CD) after definitive surgery. PATIENTS AND
      METHODS: A retrospective review was conducted on 228 patients with histologically
      proven CD who had undergone surgery to remove macroscopic disease. Recurrence was
      defined as the requirement to undergo further surgery for symptomatic CD.
      Logistic linear regression was used to evaluate the relationship between 16
      independent variables and the incidence of recurrent disease. RESULTS: The male
      to female ratio was 1:1.3, the mean age at operation was 32 years (range 11-93
      years), and the patients were followed post-operatively for a mean of 58 months
      (range 1-396 months). Survival analysis found that 29.2% of patients had a
      recurrence of CD at 5 years, and 46.0% at 10 years. Univariate analysis
      identified the following factors which were significant predictors for recurrence
      an abscess as an indication for surgery, the absence of Mesalazine/Sulphasalazine
      therapy in the preoperative period, length of follow up, development of post
      operative septic complications (abscess, anastomotic leak, fistula formation),
      and the presence of anal disease (perianal fistula, abscess, rectovaginal
      fistula, anal ulceration). The only significant independent predictors for
      recurrence were follow-up time (P=0.04, odds ratio (OR) 1.01, 95% confidence
      interval (CI) 1.00-1.01) and the absence of preoperative
      Mesalazine/Sulphasalazine therapy (P=0.05, OR 2.02, 95% CI 0.99-4.13).
      CONCLUSION: The results suggest that the use of Mesalazine/Sulphasalazine before
      surgery influenced the subsequent recurrence of CD. The clinical relevance of
      this observation requires further validation.

PMID- 12791003
TI  - Lessons from laparoscopic surgery-a fresh look at post-operative management after
      major colorectal procedures.
AB  - OBJECTIVE: Laparoscopy holds promise of exciting advances in colorectal surgery,
      yet the data we require to draw appropriate evidence-based conclusions on its
      apparent advantages are sadly lacking. In the meantime, our focus on improved
      recovery after major colorectal resections has changed the way we manage patients
      after open surgery. METHODS: A literature review was undertaken to collect
      published data on laparoscopic colorectal surgery. In addition, data on newer
      developments in open colorectal surgery were collected. RESULTS: Although there
      are many published data in laparoscopic colorectal surgery, very few are
      randomized and controlled. It is clear that, at least in the short to medium
      term, oncological outcomes are comparable to open surgery. There are data
      suggesting advantages, including less immune suppression, faster recovery with
      earlier feeding, less ileus, shorter length of stay and earlier return to normal
      activity. CONCLUSION: Unfortunately, due to study design the data are largely not
      comparable with open surgery data, and open surgery itself has changed to some
      extent recently. We must encourage recruitment of patients into current ongoing
      randomized controlled trials of laparoscopic and open surgery and await the
      results.

PMID- 12791004
TI  - A simple, inexpensive, life-saving way to perform iterative laparotomy in
      patients with severe intra-abdominal sepsis.
AB  - Between 1 June 1993 and 31 December 1998, 17 patients underwent temporary
      abdominal closure with 3L urological irrigation bags, because in most cases,
      there was massive sepsis leading to the conclusion that primary closure was not
      advisable. Indicative of the seriousness of these conditions, Apache score
      averaged 19 (range 10-30). The technique consisted of suturing a double thickness
      of irrigation bags to each side of the wound, and joining the two bags in the
      midline with running sutures. Abdominal lavage with large quantities of fluid was
      performed every other day. This type of closure was used for a mean duration of
      15 days. Mean length of hospitalization was 60 days. There were only three deaths
      (17.6%). No incisional hernia occurred after the iterative laparotomies. Deleting
      patients with acute pancreatitis would have reduced the death rate to only 7%. A
      3L urological irrigation bag costs pound 11.60 (24.40 dollars CAN) while a Marlex
      mesh costs pound 81.40 (171.00 dollars CAN). We conclude that the usage of 3L
      urological plastic bags is a simple, safe and efficient method for temporary
      closure of the abdomen.

PMID- 12791005
TI  - A prospective study of genito-urinary dysfunction after surgery for colorectal
      cancer.
AB  - OBJECTIVE: To establish the incidence of impotence and urinary dysfunction after
      different forms of pelvic and colorectal surgery. PATIENTS AND METHODS: Over a
      period of one year, 78 consecutive patients, mean age 66.8 years (range 43-91
      years), underwent surgery for colorectal cancer. Genito-urinary function was
      studied by clinical assessment and a postoperative questionnaire. RESULTS: Pre
      operatively all males except one claimed to be potent. Of the 56 patients who had
      operations on the sigmoid colon and rectum, 12 (21.4%) developed urinary
      dysfunction; 6 (5 males, 1 female) had increased frequency while 6 (4 females, 2
      males) had stress incontinence. Four (12.9%) of the 31 male patients became
      impotent. Of the control 22 patients who had had operations on the ascending
      colon, one female developed stress incontinence and none of the male patients
      developed impotence. CONCLUSION: Although the introduction of autonomic nerve
      sparing techniques and total mesorectal excision (TME) may have lowered the
      incidence of genito-urinary dysfunction after rectal surgery, there remains a
      degree of morbidity compared to procedures where the rectum is not mobilized.

PMID- 12791006
TI  - Evidence-based practice in haemorrhoidectomy.
AB  - OBJECTIVE: Haemorrhoidectomy has proven long-term efficacy in the treatment of
      haemorrhoids, albeit at the price of increased pain and complications compared
      with other modalities. This study reviews the literature and describes best
      practice in the surgical treatment of haemorrhoids. METHODS: A Medline search was
      conducted using the keywords haemorrhoids or haemorrhoidectomy to identify
      clinical trials comparing different surgical treatments for haemorrhoids.
      RESULTS: Many studies were small and follow up was often short-term only.
      Surrogate measures such as post-operative pain scores and changes in anorectal
      physiology were commonly assessed in preference to efficacy in symptom reduction.
      Haemorrhoidectomy may be safely performed under general, local or regional
      anaesthesia according to patient fitness and local practice. Results of
      randomized controlled trials indicate that there open and closed techniques of
      haemorrhoidectomy are equivalent. There is no evidence to support the practice of
      laser haemorrhoidectomy. Diathermy haemorrhoidectomy achieves good haemostasis
      and permits an anal dressing to be omitted, but is not superior to conventional
      techniques. The use of preoperative lactulose and post-operative oral
      metronidazole is supported by randomized controlled trials. CONCLUSION:
      Haemorrhoidectomy is currently the most effective treatment for prolapsing
      haemorrhoids. There is little evidence to support the use of one surgical
      technique over another. With attention to detail and adjuncts to reduce post
      operative pain, haemorrhoidectomy may be performed as day surgery.

PMID- 12791007
TI  - Risk factors for, and management of anastomotic leakage in rectal surgery.
AB  - Anastomotic leakage is one of the most serious early complications of any rectal
      anastomosis. Proximal defunctioning mitigates the consequences of leakage but
      does not abolish the risk. The lower the anastomosis the higher the risks of
      leakage. There is evidence that a short colon pouch reduces the risks of leakage.
      A high index of suspicion is required to detect the early non-specific signs of
      anastomotic leakage. Urgent surgical intervention is usually required to avert a
      life threatening situation. Reports of the demise of temporary defunctioning of
      the low anastomosis are premature, and judicious use of faecal diversion should
      never be regarded as surgical temerity.

PMID- 12791008
TI  - Closure of difficult vaginal fistulas using the gracilis muscle.

PMID- 12791012
TI  - Anal incontinence.

PMID- 12791009
TI  - Exaggerated rectal adaptation - another cause of outlet obstruction.

PMID- 12791013
TI  - Pathology of inflammatory bowel diseases (IBD): variability with time and
      treatment.
AB  - The diagnosis of chronic idiopathic IBD and the differential diagnosis between
      Crohn's disease and ulcerative colitis can be made in most cases on cumulative
      clinical, radiological, endoscopical, biochemical and pathological evidence.
      Diagnostic difficulties can however, occur in fulminant colitis, in early onset
      disease and in long-standing disease. The microscopic evaluation of disease
      activity is based on the presence of active inflammation. Effective medical
      treatment has however, an influence upon the morphology and the evolution of the
      lesions and hence can affect the diagnostic features and the microscopic features
      used for the assessment of disease activity. A literature review was performed on
      clinical drug trials in IBD and the effect of the drugs upon the microscopic
      features. Several studies have shown that the diagnostic microscopic features and
      the features characteristic for disease activity vary with time and treatment.
      For an adequate analysis of biopsy samples of patients with IBD the pathologist
      should be aware of the duration of the symptoms and the type of treatment given
      to the patient.

PMID- 12791014
TI  - Outpatient hand held manometry: comparison of techniques.
AB  - OBJECTIVE: Anorectal manometry is an established important investigation in a
      number of disorders. The specialist ano-rectal laboratory is not always
      available, and a hand held manometer may be a useful tool in the outpatient
      setting to avoid an unnecessary visit to the anorectal physiology laboratory. Our
      aims were to determine whether the hand held manometer was as reliable as the
      standard system used in the anorectal laboratory, and to correctly compare the
      results from these two different techniques. PATIENTS AND METHODS: 24 patients
      visiting the Anorectal physiology laboratory were studies. Resting pressure,
      squeeze and cough pressures were recorded using the single channel hand held
      solid pressure transducer and with the dual channel pressure transducer MRP2
      recorder. The first measurement by each method is used to illustrate the
      comparison of methods, the second measurement being used to study repeatability.
      RESULTS: The two methods correlate well for resting and squeeze pressures
      (Spearman coefficient with P < 0.01 for both) The level of agreement between the
      two methods was good for resting pressure recordings with a mean difference of 15
      cm H2O. The same cannot be said for squeeze and cough pressures. Repeatability of
      both methods was good with mean differences on repeated recordings near zero.
      CONCLUSIONS: The hand held manometer is as repeatable as the laboratory but as
      some discrepancy occurs between the two methods they are not interchangeable.
      Thus the hand held manometer used alone in the outpatients Department is a useful
      screening and research tool.

PMID- 12791015
TI  - Audit of anal-sphincter repair.
AB  - OBJECTIVE: Structural damage of the anterior part of the anal sphincter is a
      major cause of faecal incontinence. Sphincter repair is the standard surgical
      treatment. This study was designed to analyse the results of anal sphincter
      repair, to identify possible predictors of outcome and to investigate the
      presence of bowel symptoms other than leakage at follow up. PATIENTS AND METHODS:
      Fifty-five women (median age 39 years, range 24-73 years) who underwent anal
      sphincter repair between 1986 and 1997 at the University Hospital of Linkoping
      answered a postal questionnaire. Current bowel function, degree of continence and
      the patients' functional result as worse, unchanged, some improvement, good or
      excellent were assessed. Good or excellent function was regarded as a successful
      result, the rest as failure. Age, duration of symptoms, type of surgery,
      morbidity and length of follow up were analysed in relation to outcome. Results
      of pre- and post-operative anal manometry, endoanal ultrasound, anal sphincter
      electromyography and pudendal nerve function were also analysed. RESULTS: After a
      median (range) follow-up period of 40 months (5-137) months, 31 (56%) patients
      rated the result as either excellent (n=10) or good (n=21). Twenty-one (38%)
      patients rated the result as some improvement (n=14), unchanged (n=6) or worse
      (n=1). In three (5%) patients a colostomy was fashioned because of failure.
      Patients >50 years at surgery (n=18) had a worse outcome (P=0.001). Successful
      outcome was correlated to increased squeeze pressures post-operatively. The
      presence of post-operative urgency (P=0.01) and loose stools (P=0.02) was more
      common in patients with poor outcome. Eight patients became continent to formed
      and liquid stool.

PMID- 12791016
TI  - Short-term functional outcome following elective surgery for complicated sigmoid
      diverticular disease: sutured or stapled end-to-end anastomosis to the proximal
      rectum?
AB  - OBJECTIVE: The aim of this retrospective non-randomized study was to evaluate the
      short-term functional outcome following elective resectional surgery for
      complicated sigmoid diverticular disease, and to compare results of patients
      having hand-sewn or stapled end-to-end colonic anastomosis to the proximal
      rectum. PATIENTS AND METHODS: Between 1983 and 1995, of 182 consecutive patients
      referred to our Institution for surgical treatment of complicated sigmoid
      diverticular disease, 137 underwent elective left hemicolectomy with primary
      colonic anastomosis to the proximal rectum, at a level above the peritoneal
      reflection. Twenty-one patients were excluded from the study because of a
      covering stoma (n=15), or a side-to-end (n=5) or side-to-side (n=1) anastomosis.
      All remaining 116 patients had an end-to-end anastomosis without covering stoma.
      Two groups were compared according to the type of anastomosis performed. Group I
      comprised the 67 patients who had a hand-sewn anastomosis, and group II the 49
      patients whose anastomosis was stapled. Outcome was assessed at 6 months after
      surgery and compared in the two groups. Assessment included specific morbidity
      (anastomotic leakage, haemorrhage, fistulation and stenosis, pelvic sepsis),
      faecal incontinence, constipation, dyschesia, daily stool frequency, and stool
      consistency. RESULTS: Preoperative patient details were comparable in both
      groups. There was no post-operative mortality, and the general morbidity rate was
      similar in both groups (P=0.85). There was no anastomotic leakage or haemorrhage,
      and no fistulation or pelvic sepsis in either group. One patient in group I, and
      two from group II, developed flatus incontinence, and a further patient from
      group II developed incontinence to liquid stool (P=0.17, group I vs group II). We
      observed better functional outcome following hand-sewn anastomosis. Three group
      II patients developed anastomotic stenosis compared with none in group I
      (P=0.04). Constipation (9% vs 28%, P=0.005) and dyschesia (18% vs 39%, P=0.03)
      were more frequent in group II. Excluding constipated patients (n=20), daily
      stool frequency was lower (mean 1.2 +/- 0.6 vs 2 +/- 1.3, P=0.0002), and more
      frequently of normal consistency (79% vs 43%, P=0.0001) in group I. Subgroup
      analysis failed to show significant differences in functional outcome in both
      groups in relation to the specific indications for surgery. CONCLUSION: These
      retrospective data suggest for the first time in the reported literature that
      hand-sewn colonic anastomosis to the proximal rectum provides a better short-term
      functional outcome than stapled anastomosis following elective resectional
      surgery for complicated sigmoid diverticulosis.

PMID- 12791017
TI  - Histological and macroscopic changes in the pelvic pouch: long-term follow up
      after restorative proctocolectomy for ulcerative colitis (UC).
AB  - OBJECTIVE: Our aim was to evaluate macroscopic and histological (inflammatory)
      changes in ileal pouch mucosa after restorative proctocolectomy with J-pouch
      ileoanal anastomosis for UC during long-term follow up. PATIENTS AND METHODS:
      Thirty-six (56%) out of 64 consecutive patients operated at our Institute during
      1985-90 underwent endoscopy of the reservoir in the years 1994 and 1998.
      Functional outcome and macroscopic changes were recorded and histological samples
      taken from the three levels of the pelvic pouch. Acute and chronic inflammation
      were graded in accordance with a well-established histopathologic scoring system.
      RESULTS: The functional outcome was unchanged in 26 (72%), became worse in eight
      (22%) and better in two (6%) cases during follow up. The number of macroscopic
      changes increased during follow up and there was a tendency for them to become
      more common in the distal pouch. Microscopic acute and chronic inflammation
      decreased during follow up. There were more severe inflammatory changes in the
      distal pouch. Both acute and chronic inflammatory scores were higher through the
      reservoir in the cases of chronic pouchitis. Chronic pouchitis occurred more
      often in males. CONCLUSION: Macroscopic and inflammatory changes in the pelvic
      pouch seem to have separate progress during long-term follow up. In chronic
      pouchitis both acute and chronic inflammation are pronounced and spread over the
      entire pelvic pouch mucosa.

PMID- 12791018
TI  - Prevention of intra-abdominal adhesions by using Seprafilm in rats undergoing
      bowel resection and radiation therapy.
AB  - OBJECTIVE: Intra-abdominal adhesions are an important surgical problem.
      Colorectal operations are a major cause of adhesive obstruction. Radiation
      therapy (RT) is frequently used as an adjuvant therapy to surgery for rectal
      cancer, though its value for colon carcinoma remains unclear. Peritoneal injuries
      including the surgical trauma, tissue ischaemia as well as RT are associated with
      peritoneal fibrinolytic activity. A sodium hyaluronate and carboxymethylcellulose
      bioresorbable membrane (Seprafilm) has been used to reduce intra-abdominal
      adhesion formation. We have investigated the effect of Seprafilm on intra
      abdominal adhesion in rats receiving RT after the resection of the left colon.
      MATERIALS AND METHODS: Thirty-two male Wistar rats were divided into two groups:
      group 1 (n=16), control (colon resection, no Seprafilm); group 2 (n=16), study
      group (colon resection and Seprafilm). All the rats received 50 Gy RT after left
      colon resection. Intra-abdominal adhesions were evaluated by grading and
      measurement of tissue-type plasminogen activator (tPA) as a tissue adhesion
      marker in peritoneal samples from the rats. tPA was determined using a
      commercially available ELISA kit. RESULTS: The levels of tPA were significantly
      increased in group 2 rats compared with those in the control group (P=0.0276). It
      was also seen that adhesions in the rats receiving Seprafilm were significantly
      less severe than those in the control group. CONCLUSION: Our findings suggest
      that the intraperitoneal administration of Seprafilm reduced the frequency and
      strength of adhesions.

PMID- 12791019
TI  - Relationship of angiogenesis and p53 protein expression in colorectal carcinomas.
AB  - OBJECTIVE: Recently, new functions have been attributed to the p53 protein,
      particularly a prominent role in the regulation of angiogenesis. Tumours
      expressing mutant forms of p53 protein may be associated with increased
      angiogenesis. The aim of this study is to investigate the relationship between
      p53 protein expression and the quantitative expression of tumour angiogenesis in
      colorectal carcinomas. PATIENTS AND METHODS: Sections from paraffin-embedded
      blocks from 46 patients with primary colorectal carcinomas that had been
      completely removed were analysed. p53 protein expression and all vascular
      structures were evaluated by immunohistochemistry. The vessel parameters of
      angiogenesis including vascular surface density (VSD), number of vessels per mm2
      (NVES) and number of vessels in unit area (n) were assessed by morphometry. Mann
      Whitney U-test was used for comparing the extent of neovascularization in p53
      positive and -negative cases. RESULTS: Twenty-four (52%) cases were p53+ and 22
      (48%) were p53-. Mean VSD, NVES and n values for p53 protein-positive and 
      negative groups were as follows: VSD 96.7 +/- 65.4/mm vs 79.6 +/- 45.24/mm; NVES
      104.8 +/- 97.5/mm2 vs 62.2 +/- 44.3/mm2; n 79.7 +/- 74.2 vs 52 +/- 35.7,
      respectively. There was no association between the angiogenesis parameters and
      p53-positive and -negative cases, when VSD (P=0.226) or n (P=0.176) were
      considered, but a statistically significant difference was obtained for NVES
      values (P=0.035). CONCLUSION: The authors concluded that tumoural angiogenesis
      assayed by morphometric investigation in colorectal carcinomas might be related
      to p53 protein expression when NVES is considered. This finding supports the
      possible role of p53 protein in increased angiogenesis in colorectal tumours.

PMID- 12791020
TI  - One-stage procedure in non-elective surgery for diverticular disease
      complications.
AB  - OBJECTIVE: Admission of patients with acute complications of diverticular disease
      is frequent and operative management remains controversial. The aim of this study
      was to investigate the efficacy and safety of resection, intra-operative colonic
      lavage and primary anastomosis in patients who require urgent laparotomy to treat
      complications of diverticular disease. PATIENTS AND METHODS: From January 1992 to
      December 1999, 124 surgical patients underwent emergency operation for
      complicated diverticular disease. Resection, intra-operative colonic lavage and
      primary anastomosis were carried out in 55 patients: four with obstruction, two
      with massive bleeding and 49 with diverticulitis. In the diverticulitis group, 33
      (67.3%) patients presented with localized peritonitis and 16 (32.7%) with
      generalized purulent peritonitis. No patient with faecal peritonitis was treated
      by a one-stage procedure. RESULTS: One or more complications were detected in 25
      patients (45.4%). Four patients (7.2%) required reintervention. Mortality
      occurred in four patients (7.2%). Two patients (3.6%) presented with anastomotic
      leakage. Wound infection was detected in 16 cases (29%). The overall mean (s.d.)
      Hospital stay was 18.5 (12.1) days. CONCLUSION: Resection, intra-operative
      colonic lavage and primary anastomosis provide an alternative procedure for
      achieving one-stage resection in selected patients who require emergency
      operation for complication of diverticular disease.

PMID- 12791021
TI  - Midline or transverse abdominal incision for right-sided colon cancer-a
      randomized trial.
AB  - OBJECTIVE: The influence of the type of abdominal incision on post-operative pain
      and pulmonary function was investigated in patients operated upon for a right
      sided cancer of the large bowel. PATIENTS AND METHODS: Fifty-three patients
      scheduled for a right hemicolectomy due to a right-sided colon cancer were
      randomized to a median vertical (M) or a transverse incision (T). Forty patients,
      23 with a M and 17 with a T incision, completed the study and could be evaluated.
      Pain at rest and after physical activity was assessed with a visual analogue
      scale, and was also measured as reflected in the need for analgesics. Respiratory
      function was assessed with pre- and post-operative spirometry. RESULTS: Pain
      after activity was significantly less in patients with a T incision. This group
      also needed less analgesia. Vital capacity (VC) and forced expiratory volume in 1
      s (FEV 1.0) were profoundly reduced after surgery in both groups of patients, but
      improvement of respiratory function was faster in patients with a transverse
      incision. No problem with access to the operative field was noted. CONCLUSION: We
      conclude that a transverse incision is preferable to a midline incision and
      should be used in right hemicolectomy. This abdominal incision reduces effort
      induced pain and interferes less with post-operative pulmonary function, and may
      reduce the risk of pulmonary complications.

PMID- 12791023
TI  - Randomized controlled trials in colorectal disease; a review of recent trials.

PMID- 12791024
TI  - Introducing the circular stapling device atraumatically with the use of a second
      anvil.

PMID- 12791022
TI  - One-step vs two-step procedure in dynamic graciloplasty.
AB  - OBJECTIVE: Dynamic graciloplasty, a proven treatment for end-stage faecal
      incontinence, requires transposition of the gracilis muscle around the anal canal
      and implantation of a pulse generator and intramuscular electrodes. In view of
      the risk of infection around the implanted material the implantation was
      initially not performed in combination with the perineal procedure but 6 weeks
      later. Sparing the patients an extra operation, however, might be justified if
      morbidity is not increased. This study aimed to compare the combined single-stage
      with the two-stage procedures. PATIENTS AND METHODS: Two groups of 13 patients
      were admitted to this prospective, matched control study according to waiting
      list ranking. They were matched for age, gender and aetiology. Group I had
      transposition and transplantation combined, group II underwent these procedures
      separately with a 6-week interval. Continence, manometry, stimulation parameters,
      quality of life results and adverse events were recorded. RESULTS: After a mean
      521-day follow up infection rates were comparable in both groups, as were
      continence rates, morbidity, anal manometry, stimulation parameters and quality
      of life. CONCLUSION: Outcome, morbidity and quality of life seem to be
      comparable. A single procedure avoids the need for an extra admission and
      operation, so the one-stage approach should be the standard procedure in dynamic
      graciloplasty.

PMID- 12791025
TI  - Introducing the circular stapling device atraumatically with the use of a second
      anvil.

PMID- 12791026
TI  - Introducing the circular stapling device atraumatically with the use of a second
      anvil.

PMID- 12791027
TI  - A prospective evaluation of the introduction of circumferential stapled anoplasty
      in the management of haemorrhoids and mucosal prolapse.

PMID- 12791034
TI  - Overestimation of genetic risks owing to small sample sizes in cardiovascular
      studies.
AB  - We sought evidence of publication bias to explain conflicting findings in studies
      of angiotensin-converting enzyme deletion polymorphism (ACE D) and glycoprotein
      IIIa PlA2 (PLA2) polymorphism and the risk of myocardial infarction. Factor 5
      Leiden (F5L), a well-established thrombotic risk factor, served as an internal
      comparison. We conducted systematic reviews of published studies involving ACE D,
      PLA2, F5L and relevant outcomes, searching medline (January 1990 through
      February, 2001), bibliographies, and meta-analyses. Random effects pooled odds
      ratios (95% confidence interval) for cardiovascular outcomes were as follows:
      PLA2 (n = 13,167 subjects): 1.13 (1.02, 1.26); ACE D (n = 42,140 subjects): 1.22
      (1.11, 1.35); and F5L (n = 27,277 subjects): 4.43 (3.65, 5.38). However, funnel
      plots of ACE D and PLA2, but not F5L, showed an inverse relationship between
      sample size and odds ratios for ACE D (p = 0.02) and PLA2 (p = 0.04) but not F5L
      (p = 0.65) by Egger's test for potential publication bias. Despite research-based
      genotyping of over 50,000 subjects, the overall risk for myocardial infarction as
      a result of PLA2 and ACE D remains doubtful. Our study provides a clear example
      of how publication of underpowered studies can spuriously implicate polymorphisms
      as genetic risk factors.

PMID- 12791035
TI  - Association of the myocilin mt.1 promoter variant with the worsening of
      glaucomatous disease over time.
AB  - A major variant of myocilin (MYOC) [TIGR/MYOC mt.1 (-1000 C/G)], present in the
      gene's promoter, is found to be associated with more rapid progression of the
      glaucoma disease state. Time-to-event analyses using the Cox proportional hazards
      model produced substantial statistical evidence that this TIGR/MYOC mt.1(+)
      variant accelerates worsening for both optic disc and visual field measures of
      disease progression. These analyses were based on evaluations of 147 patients
      with primary open-angle glaucoma (POAG) over 35 years of age with an average
      follow-up of approximately 15 years. Our analyses showed that there are
      independent effects of the variant on disease progression, taking into account
      other relevant disease-related baseline risk factors, including age, family
      history, initial drug treatment, initial surgical treatment, diabetes, gender,
      myopia, and initial disease severity. The finding that a TIGR/MYOC mt.1(+)
      determination provided a strong marker for glaucoma progression, above and beyond
      the other baseline risk factors, suggests a clinical utility in testing for this
      promoter genotype.

PMID- 12791036
TI  - A cluster of autosomal recessive spondylocostal dysostosis caused by three newly
      identified DLL3 mutations segregating in a small village.
AB  - In 1982, one of us reported a cluster of eight individuals affected by
      spondylocostal dysostosis (SD, MIM 277300) in four nuclear families indigenous to
      a village from eastern Switzerland. We tested the hypothesis that the molecular
      basis for this cluster was segregation of a single mutation in the DLL3 gene,
      recently linked to SD. Marker haplotypes around the DLL3 locus contradicted this
      hypothesis as three different haplotypes were seen in affected individuals, but
      sequence analysis showed that three unreported DLL3 mutations were segregating: a
      duplication of 17 bp in exon 8 (c.1285-1301dup), a single-nucleotide deletion in
      exon 5 (c.615delC), and a R238X nonsense mutation in exon 6. Contrary to our
      initial assumption of a single allele segregating in this small community, three
      different pathogenic alleles were observed, with a putative founder mutation
      occurring at the homozygous state but also compounding with, and thus revealing,
      two other independent mutations. As all three mutations predict truncation of the
      DLL3 protein and loss of the membrane-attaching domain, the results confirm that
      autosomal recessive spondylocostal dysostosis represents the null phenotype of
      DLL3, with remarkable phenotypic consistency across families.

PMID- 12791037
TI  - Evidence that the Cys282Tyr mutation of the HFE gene originated from a population
      in Southern Scandinavia and spread with the Vikings.
AB  - Hereditary hemochromatosis has been recognized as a clinical disorder for more
      than 100 years. The common form of the disorder is caused by the Cys282Tyr
      mutation (C282Y) of the HFE gene. Hereditary hemochromatosis affects
      predominantly people of Northern European origin. The C282Y mutation probably
      occurred on a single chromosome carrying the ancestral hemochromatosis haplotype,
      which subsequently was spread by emigration and the founder effect. It has been
      estimated that the C282Y mutation appeared 60-70 generations ago. It was
      initially suggested that the ancestral C282Y mutation occurred within the Celtic
      group of peoples. However, we hypothesize that the distribution of the C282Y
      mutation in Europe is more consistent with an origin among the Germanic Iron Age
      population in Southern Scandinavia. From this area, the mutation could later be
      spread by the migratory activities of the Vikings. The aim of the present study
      was to evaluate the validity of these two hypotheses. Several arguments are in
      favor of the 'Viking hypothesis': first, the highest frequencies (5.1-9.7%) of
      the C282Y mutation are observed in populations in the Northern part of Europe,
      i.e. Denmark, Norway, Sweden, Faeroe Islands, Iceland, Eastern part of England
      (Danelaw) and the Dublin area, all Viking homelands and settlements. Second, the
      highest allele frequencies are reported among populations living along the
      coastlines. Third, the frequencies of the C282Y mutation decline from Northern to
      Southern Europe. Intermediate allele frequencies (3.1-4.8%) are seen in the
      populations in Central Europe, which is the original Celtic homeland. Low allele
      frequencies (0-3.1%) are recognized in populations in Southern Europe and the
      Mediterranean.

PMID- 12791038
TI  - Germline mutations of the MEN1 gene in Korean families with multiple endocrine
      neoplasia type 1 (MEN1) or MEN1-related disorders.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome
      characterized by the combined occurrence of tumours of the parathyroid glands,
      pancreatic islet cells and anterior pituitary gland. Mutation analysis of the
      MEN1 gene has enabled the genetic diagnosis of patients with MEN1. Two MEN1
      related disorders - familial isolated hyperparathyroidism (FIHP) and familial
      pituitary adenoma - are considered to be variants of MEN1, or at least to be
      incompletely expressed variants. Germline mutations of the MEN1 gene have been
      reported in some with FIHP, but familial pituitary adenoma usually lacks the MEN1
      mutation and has been described as a genetically distinct disorder. In this work,
      we investigated five Korean families with MEN1, one family with FIHP and one
      family with familial pituitary adenoma. Polymerase chain reaction (PCR)-based
      single-strand conformation polymorphism (PCR-SSCP) analysis, denaturing high
      performance liquid chromatography (DHPLC) and sequencing were used to detect the
      MEN1 mutations. Screening of the genetic variations of the MEN1 gene revealed
      four germline mutations in five typical MEN1 families. All four germline
      mutations led to truncated proteins or a change in the amino acids of the
      functional domains. In this study, we identified three novel MEN1 germline
      mutations (969C >A, 973G >C and 1213C >T) and one previously reported mutation
      (200-201insAGCCC). The frequency of the MEN1 germline mutation in Korean MEN1
      families (four of five; 80%) was similar to those reported previously. In
      accordance with previous studies, no MEN1 germline mutation was detected in two
      families with FIHP or familial pituitary adenoma.

PMID- 12791039
TI  - Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X
      syndrome.
AB  - Recently it has been reported that late-onset tremor, gait unsteadiness and
      dementia can be associated with brain atrophy in males of normal intelligence and
      the pre-mutation carrier state of the fragile X syndrome. We have shown, by means
      of a telephone survey, that this association is probably causal rather than
      coincidental. These findings have uncovered another testable cause of late-onset
      neurological symptoms in males, which also has serious genetic implications for
      their daughters who are at risk of having sons with full mutations causing mental
      handicap - the fragile X syndrome.

PMID- 12791040
TI  - Gaucher's disease: identification of novel mutant alleles and genotype-phenotype
      relationships.
AB  - A sequencing protocol for the acid beta-glucosidase (GCase) gene (GBA) was
      developed using a long-range PCR template. This protocol has an advantage of
      greater DNA yields over similar strategies. Seven Gaucher's disease patients had
      four novel and five other rare alleles. A non-pseudogene in-frame deletion
      (g.2600-2602delTAC) and a new complex mutation (null allele) were identified in
      Gaucher's disease type 1, i.e. the g.2600-2602delTAC deletion is associated with
      the non-neuronopathic variant. An F251L allele was found in a baby with the
      collodion skin phenotype. Three mutant alleles were identified in a single
      primary family with type 3. The patients' father at 45 years is healthy and is
      heteroallelic for the G202R and E326K alleles. Family studies indicated that
      E326K is in trans to G202R and L444P, and that isolated E326K is non-pathogenic
      in this family. A rare mutation R257Q was identified in a type 2 patient,
      providing an association with neuronopathic disease. A genotype L444P/L444P was
      noted in a 22-year-old non-neuronopathic patient. Complete gene sequencing showed
      a new complex allele consisting of L444P and g.7741T > C in the 3' UTR. Three
      additional complex alleles also involved the 3' UTR. Complete gene
      characterization in Gaucher's disease should allow greater insights into the
      correlation of specific alleles with phenotype.

PMID- 12791041
TI  - Frequencies of gap- and tight-junction mutations in Turkish families with
      autosomal-recessive non-syndromic hearing loss.
AB  - Mutations in genes encoding gap- and tight-junction proteins have been shown to
      cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26
      (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families
      with autosomal-recessive inherited non-syndromic sensorineural hearing loss
      (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2-35delG
      mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2
      35delG in the normal Turkish population was found to be 1.17% (five in 429). In
      addition to the described W24X, 233delC, 120delE and R127H mutations, we also
      identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R
      allele was inherited on the same haplotype as V27I and E114G polymorphisms. As
      little is known about the mutation frequencies of most other recently identified
      gap- and tight-junction genes as a cause for hearing loss, we further screened
      our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), DeltaGJB6-D13S1830 (Cx30)
      and the gene encoding the tight-junction protein, claudin 14 (CLDN14). Several
      novel polymorphisms, but no disease-associated mutations, were identified in the
      CLND14 and GJA1 genes, and we were unable to detect the DeltaGJB6-D13S1830
      deletion. A novel putative mutation, P223T, was found in the GJB3 gene in
      heterozygous form in a family with two affected children. Our data shows that the
      frequency of GJB2 mutations in Turkish patients with autosomal-recessive NSSHL
      and the carrier rate of the GJB2-35delG mutation in the Turkish population, is
      much lower than described for other Mediterranean countries. Furthermore,
      mutations in other gap- and tight-junction proteins are not a frequent cause of
      hearing loss in Turkey.

PMID- 12791042
TI  - XL PCR for the detection of large trinucleotide expansions in juvenile
      Huntington's disease.
AB  - Juvenile Huntington's disease (HD) becomes clinically manifest before 20 years of
      age. The diagnosis of HD is based on family history, characteristic clinical
      findings, and the detection of an expansion of a CAG polyglutamine tract in the
      Huntingtin gene. Juvenile HD is characterized by paternal anticipation and large
      CAG expansions that may be missed using routine molecular analysis. We have
      developed an easy, rapid, and reliable modified PCR method using XL (Extra Long)
      PCR that allowed us to diagnose one of the youngest children reported with
      juvenile HD. Without this innovation we would not have been able to demonstrate
      the large CAG expansion. This assay could become part of a standard protocol for
      HD testing in molecular diagnostic laboratories.

PMID- 12791043
TI  - Semen cryoconservation in men with AZFc microdeletion.

PMID- 12791044
TI  - A quantitative polymerase chain reaction method for determining copy number
      within the Prader-Willi/Angelman syndrome critical region.

PMID- 12791045
TI  - A novel mutation in the TWIST gene, implicated in Saethre-Chotzen syndrome, is
      found in the original case of Robinow-Sorauf syndrome.

PMID- 12791046
TI  - Introducing evidence based clinical reviews in Veterinary Dermatology.

PMID- 12791047
TI  - Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy
      of canine atopic dermatitis.
AB  - The efficacy of pharmacological interventions used to treat canine atopic
      dermatitis, excluding fatty acid supplementation and allergen-specific
      immunotherapy, was evaluated based on the systematic review of prospective
      clinical trials published between 1980 and 2002. Studies were compared with
      regard to design characteristics (randomization generation and concealment,
      masking, intention-to-treat analyses and quality of enrolment of study subjects),
      benefit (improvement in skin lesions or pruritus scores) and harm (type, severity
      and frequency of adverse drug events) of the various interventions. Meta-analysis
      of pooled results was not possible because of heterogeneity of the drugs
      evaluated. Forty trials enrolling 1607 dogs were identified. There is good
      evidence for recommending the use of oral glucocorticoids and cyclosporin for the
      treatment of canine atopic dermatitis, and fair evidence for using topical
      triamcinolone spray, topical tacrolimus lotion, oral pentoxifylline or oral
      misoprostol. Insufficient evidence is available for or against recommending the
      prescription of oral first- and second-generation type-1 histamine receptor
      antagonists, tricyclic antidepressants, cyproheptadine, aspirin, Chinese herbal
      therapy, an homeopathic complex remedy, ascorbic acid, AHR-13268, papaverine,
      immune-modulating antibiotics or tranilast and topical pramoxine or capsaicin.
      Finally, there is fair evidence against recommending the use of oral arofylline,
      leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.

PMID- 12791048
TI  - A modified biopsy technique to improve histopathological evaluation of avian
      skin.
AB  - Skin biopsies are a viable diagnostic tool in avian dermatology, however, the
      thinness of avian skin makes it difficult to prevent rolling and contraction of
      skin biopsy specimens during collection and fixation. The difficulty orienting
      such rolled samples during processing ultimately interferes with the
      establishment of a histopathological diagnosis. We describe a modified skin
      biopsy procedure for obtaining avian skin biopsy specimens. In this technique
      nontranslucent self-adhesive tape (Scotch tape) was attached to skin biopsy sites
      before obtaining skin biopsies using a standard skin biopsy punch instrument. A
      total of 23 skin biopsy specimens were obtained: 15 from nonfeathered skin of 12
      normal Hispaniolan parrots, 3 from feathered skin of 2 normal birds and 5 from
      feathered skin of 3 psittacines presented for pathologic feather-picking. All 23
      skin specimens consistently adhered to the tape during the biopsy procedure. The
      specimens were fixed in 10% neutral phosphate-buffered formalin. During
      processing, no curling or rolling of specimens occurred, and all specimens could
      be easily orientated for correct trimming and subsequent histopathological
      evaluation. The tape technique did not produce any appreciable artefacts.
      Remnants of the tape were microscopically evident above the stratum corneum
      assuring that none of the stratum corneum was lost during processing. Obtaining
      avian skin biopsy specimens using this modified tape technique is easy and
      ensures flat fixation of the skin biopsy specimens, which later allows trimming
      at right angles, and through the longitudinal diameter of feather follicles for
      accurate histopathologic evaluation.

PMID- 12791049
TI  - Comparative efficacies of oral ketoconazole and terbinafine for reducing
      Malassezia population sizes on the skin of Basset Hounds.
AB  - The objective of this study was to compare the efficacy of oral ketoconazole and
      terbinafine for reducing population sizes of Malassezia yeasts on canine skin.
      Twenty-one Basset Hounds were randomised in three groups of seven according to
      Malassezia populations. Dogs in the first group were treated by oral
      administration of ketoconazole (Ketofungol) 200 mg, Janssen-Cilag) at 10 mg x kg
      1, every 24 h with food, for 3 weeks. Dogs in the second group were treated by
      oral administration of terbinafine (Lamisil) 250 mg, Novartis) at 30 mg x kg-1,
      every 24 h with food, for 3 weeks. The seven remaining dogs were used as
      controls. Malassezia population sizes were assessed by use of contact plates on
      four cutaneous sites at days 7, 14 and 21. Both ketoconazole and terbinafine were
      effective in reducing the baseline levels of Malassezia organisms with no
      significant difference between the two drugs. In further studies, oral
      terbinafine should be evaluated for the management of canine cases of Malassezia
      dermatitis.

PMID- 12791050
TI  - Concurrent follicular dysplasia and interface dermatitis in Boxer dogs.
AB  - Recurrent or persistent follicular dysplasia and interface dermatitis are
      described in nine Boxers. Data on age, sex, seasonality of alopecia and
      histopathological features of the follicular dysplasia in these nine Boxers are
      comparable with those described in previous reports. The interface dermatitis was
      characterized by multifocal annular crusted lesions confined to the areas of
      follicular dysplasia. The inflammatory lesions were neither pruritic nor painful
      and affected dogs were otherwise healthy. Histopathologically the clinically
      inflammatory lesions were characterized as an interface dermatitis.
      Immunohistochemical studies failed to demonstrate immunoglobulins or complement
      at the basement membrane zone or within blood vessel walls. In dogs with
      recurrent or persistent disease, the follicular dysplasia and interface
      dermatitis ran identical, concurrent courses of spontaneous remission and
      recurrence, or persistence, respectively. One dog with persistent disease was
      treated successfully with tetracycline and niacinamide for the interface
      dermatitis, and melatonin for the follicular dysplasia. Although the
      aetiopathogenesis of this newly described condition and the relationship between
      the two histological reaction patterns are not known, photoperiod and genetic
      predisposition appear to play a role.

PMID- 12791052
TI  - Acrochordonous plaques in two Bulldogs and a Pug dog.
AB  - Acrochordons or fibroepithelial polyps are exophytic to pedunculated tumour-like
      lesions of the skin reported to occur in humans and animals. We report here a new
      and unusual presentation of numerous, closely associated acrochordons forming a
      plaque, preferentially located at the dorsal neck of two Bulldogs and a Pug dog.
      Histopathologically these plaques were characterized by oedematous to fibrous
      cores enclosed by normal to moderately hyperplastic epidermis. We propose the
      name acrochordonous plaque to reflect the clinical lesion and the
      histopathological appearance of numerous, closely spaced acrochordons. Although
      the aetiology of these lesions remains unclear, there may be a breed
      predisposition for Bulldog-like breeds.

PMID- 12791051
TI  - Effects of propofol-induced sedation on intradermal test reactions in dogs with
      atopic dermatitis.
AB  - We compared the effect of propofol and saline control on intradermal test
      reactions in dogs with atopic dermatitis undergoing outpatient intradermal
      testing (IDT). Nineteen dogs were used in this clinical study. Patients were
      randomly allocated to receive either intravenous (IV) propofol or IV 0.9% saline,
      and IDT was performed on the right or left (randomized) lateral thorax. One
      investigator, unaware of the treatments, interpreted all IDT results. Injection
      sites were analysed using a subjective and objective method. A value of P <or=
      0.05 was considered significant. When all injection sites were subjectively
      analysed for reactions >or= 1+ on all dogs, significantly more positive sites
      were apparent during propofol sedation than during saline administration. In
      addition, the greater number of individual dogs experiencing more positive
      reactions >or= 1+ during propofol sedation was significant. When subjectively
      analysing reactions >or= 2+, the greater number of positive reactions and the
      greater number of dogs with more positive reactions observed during propofol
      treatment was not significantly different from the saline control. When analysed
      objectively, the greater number of positive reactions observed during propofol
      sedation was not significant. A greater number of dogs had higher subjective
      scores and larger objective measurements during propofol sedation compared with
      saline administration. In summary, propofol sedation was associated with an
      overall greater number of positive IDT reactions compared with the saline
      control. Although not always significant, this difference should be considered
      when choosing propofol for skin testing dogs with atopic dermatitis.

PMID- 12791053
TI  - Editorial: Maternal malaria: time for action.

PMID- 12791054
TI  - Safety, efficacy and determinants of effectiveness of antimalarial drugs during
      pregnancy: implications for prevention programmes in Plasmodium falciparum
      endemic sub-Saharan Africa.
AB  - Plasmodium falciparum malaria in pregnancy poses substantial risk to a pregnant
      woman and her neonate through anaemia and low birth weight (LBW), respectively,
      and is responsible for up to 35% of preventable LBW in malaria-endemic areas.
      Chemoprophylaxis or intermittent preventive treatment (IPT) with an effective
      antimalarial can ameliorate the adverse effects of malaria during pregnancy.
      Current guidelines from the WHO recommend that women in highly malarious areas
      receive IPT with an effective antimalarial. Two central considerations in
      evaluating drugs for use during pregnancy are safety for the mother and her
      foetus and effectiveness, which is determined by efficacy, cost, availability,
      deliverability and acceptability of the drug. These factors may be scored and
      potential drugs or drug combinations ranked in order of potential effectiveness
      for use in prevention programmes. The seven most promising regimens are all IPT,
      primarily because they are more easily delivered and less expensive than
      chemoprophylaxis. Currently, IPT with sulphadoxine-pyrimethamine (SP) is more
      likely to have the best overall effectiveness in preventing adverse outcomes
      associated with malaria in pregnancy. Its low cost, wide availability, easy
      deliverability and acceptability make it the clear choice in countries where
      efficacy of the drug remains good. For countries where resistance to SP is rising
      or already high, amodiaquine (alone or in combination with SP or artesunate)
      artesunate + SP, chlorproguanil-dapsone (with and without artesunate) and
      artemether-lumefantrine require urgent evaluation for use in pregnancy.

PMID- 12791055
TI  - The association between protein-energy malnutrition, malaria morbidity and all
      cause mortality in West African children.
AB  - Both malaria and protein-energy malnutrition (PEM) are highly prevalent in young
      children of sub-Saharan Africa, and the association between PEM and malaria
      continues to be discussed controversially. We analysed the association between
      PEM, malaria morbidity and all-cause mortality in a cohort of 709 children aged 6
      30 months in a malaria holoendemic rural area of Burkina Faso. Study children
      were followed over the main malaria transmission period (June-December) in 1999
      through longitudinal malaria surveillance complemented by three cross-sectional
      clinical surveys. There was no association between PEM and malaria morbidity, but
      malnourished children had a more than two-fold higher risk of dying than non
      malnourished children.

PMID- 12791056
TI  - Changes in house design reduce exposure to malaria mosquitoes.
AB  - House design may affect an individual's exposure to malaria parasites, and hence
      to disease. We conducted a randomized-controlled study using experimental huts in
      rural Gambia, to determine whether installing a ceiling or closing the eaves
      could protect people from malaria mosquitoes. Five treatments were tested against
      a control hut: plywood ceiling; synthetic-netting ceiling; insecticide-treated
      synthetic-netting ceiling (deltamethrin 12.5 mg/m2); plastic insect-screen
      ceiling; or the eaves closed with mud. The acceptability of such interventions
      was investigated by discussions with local communities. House entry by Anopheles
      gambiae, the principal African malaria vector, was reduced by the presence of a
      ceiling: plywood (59% reduction), synthetic-netting (79%), insecticide-treated
      synthetic-netting (78%), plastic insect-screen (80%, P < 0.001 in all cases) and
      closed eaves (37%, ns). Similar reductions were also seen with Mansonia spp.,
      vectors of lymphatic filariasis and numerous arboviruses. Netting and insect
      screen ceilings probably work as decoy traps attracting mosquitoes into the roof
      space, but not the room. Ceilings are likely to be well accepted and may be of
      greatest benefit in areas of low to moderate transmission and when used in
      combination with other malaria control strategies.

PMID- 12791057
TI  - Self-reported compliance with last malaria treatment and occurrence of malaria
      during follow-up in a Brazilian Amazon population.
AB  - The objective of this study was to describe the association between self-reported
      compliance with last malaria treatment (CMT) and occurrence of malaria during
      follow-up, controlling for current risk factors. We conducted a prospective open
      cohort study in Leonislandia, a rural area of Peixoto de Azevedo City, in the
      Amazon region of Mato Grosso, Brazil. A total of 414 individuals were interviewed
      at baseline regarding CMT and followed-up for either 8 or 4 months to assess
      malaria incidence. The associations between CMT and occurrence of malaria were
      examined through multiple linear regression (when the outcome was malaria episode
      frequency) or Cox regression (when the outcome was time to malaria onset). Poor
      CMT (prior to baseline) was identified as an important predictor of the
      occurrence of subsequent malaria episodes during follow-up among individuals with
      an indication of being less immune - those whose first malaria episode was
      relatively recent or those who had an increased number of malaria episodes during
      the last 2 years. Moreover, surprisingly, it seems that for individuals who are
      probably more immune (individuals who had experienced their first malaria episode
      more than 4.5 years previously or those with few or no malaria episodes during
      the last 2 years), CMT was found to be a poor predictor of increased risk of
      subsequent malaria. These findings provide compelling evidence for the need to
      further study CMT and its effect on malaria outcomes.

PMID- 12791058
TI  - The prevalence of Anopheles (Diptera: Culicidae) mosquitoes in Sekong Province,
      Lao PDR in relation to malaria transmission.
AB  - A longitudinal study was conducted on the prevalence of Anopheles in three
      malaria endemic villages in Sekong province, in the southern region of Lao PDR,
      from August 2000 to October 2001. All night, human landing collections took place
      in August and October 2000 and April and October 2001, and blood smears were
      taken for malaria parasites during the same period. Mosquitoes were tested for
      sporozoite antigen using enzyme-linked immunosorbent assay. In August 2000 (wet
      season) and April 2001 (dry season) the ovaries of the mosquitoes were examined
      for parity. A total of 16 species of Anopheles were caught in the study sites of
      which An. dirus A, An. maculatus sl and An. jeyporiensis were positive for
      sporozoites. The entomological inoculation rate (EIR) ranged from 0.06 to 0.25.
      There was a good correlation between EIR and vectorial capacity in the wet
      season, especially in Pai Mai where the prevalence of malaria was also high
      during the wet seasons (11.8 and 10.53). An. dirus A showed ambivalence in their
      choice of feeding as approximately 50% attacked man indoors and an equal
      proportion outdoors. An dirus A was the main vector in Pai Mai. The parous rate
      did not significantly differ between the wet and dry season, although it was
      higher in the dry season. In Takaio the parasite prevalence ranged from 8.7% (dry
      season) to 37.1% (wet season) and An. jeyporiensis was the vector, and the risk
      of infection was 0.85 in the dry season while 0.99 in the wet season. In Toumgno
      An. maculatus sl was the vector and infection was found only in August and
      October 2000. However, malaria prevalence ranged from 9.69 to 20.4% and was
      equally high in the dry season. Cattle were also present close to the houses in
      all the villages and this might be a contributory factor in the prevalence of
      malaria.

PMID- 12791060
TI  - A Piot model to analyse case management in malaria control programmes.
AB  - At the beginning of the 21st century, malaria remains one of the most important
      public health problems in the world. An important control strategy to address
      this burden is adequate case management of malaria patients. The success of this
      strategy, however, does not solely depend on diagnosis and treatment, but also on
      a sequence of steps that patients have to take when they are ill. Only when
      patients go through all these steps successfully will they be cured. In this
      paper, a model is presented in which these steps are described. The model
      provides a framework for analysing this type of malaria control strategy and for
      identifying the most critical challenges faced. Furthermore, the model is used to
      analyse recent literature on case management as part of malaria control
      programmes in order to highlight current knowledge, core issues and constraints,
      and to make recommendations for programme development and research.

PMID- 12791059
TI  - Malaria dipsticks beneficial for IMCI in Cambodia.
AB  - OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) approach and
      new clinical treatment guidelines to control malaria among children less than 5
      years old were introduced recently in Cambodia. This study was conducted to
      finalize the malaria part of the national IMCI fever chart. METHODS: A total of
      323 sick children 2-59 months old were studied at rural health centres in
      northern Cambodia from February to April 2000. Cases with fever (by axillary
      temperature or history) or anaemia (by palmar pallor) were tested with dipsticks
      for Plasmodium falciparum and Plasmodium vivax in high and low malaria risk areas
      and, if positive, treated with anti-malarials. RESULTS: The draft IMCI chart
      identified children with malaria safely and effectively (sensitivity 14 of 15,
      approximately 93% and specificity 292 of 308, approximately 95%). The study
      confirmed the potential of malaria dipsticks as a part of IMCI case management.
      CONCLUSION: The Cambodian Ministry of Health will use the studied malaria chart
      during the Early Implementation Phase of IMCI. Dipsticks able to detect P.
      falciparum and P. vivax with high sensitivity and acceptable cost will be needed
      for this purpose. To promote the rational use of dipsticks, the National Centre
      for Malaria Control, Parasitology and Entomology (Centre National de Malaridogie,
      Parasitologie et Entomologie, CNM) should list all known malaria risk areas in
      the country and prepare detailed local maps guiding case management especially in
      transitional zones.

PMID- 12791061
TI  - Should family planning clinics provide clinical services for sexually transmitted
      infections? A case study from Cote d'Ivoire.
AB  - OBJECTIVES: To evaluate the quality and usefulness of integrated sexually
      transmitted infection (STI) care at non-governmental family planning (FP) clinics
      in Cote d'Ivoire. METHODS: Evaluation components included: (1) a survey measuring
      the prevalence of STI and the predictive value of the Ivorian vaginal discharge
      treatment algorithm, (2) client exit interviews, (3) direct observations of
      client-provider contacts, (4) the monitoring of the clinics' workload and
      available equipment and supplies and (5) interviews of programme managers and FP
      providers. RESULTS: Among 368 FP clients surveyed, the prevalence of Neisseria
      gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, B. vaginosis and
      Candida albicans were respectively 1.6, 5.7, 7.1, 44.8 and 5.2%. The positive
      predictive value of the national algorithm for the detection of cervicitis was
      only 6.3%, and was 17.9% among a subgroup of young, single women. Of 200 clients
      interviewed, 96% were satisfied with the services and 95% would return to the FP
      clinic if they had genital problems. In 215 observed client-provider contacts,
      88% of 94 STI cases were correctly managed. Programme managers and providers
      reported no substantial work overload as a result of the integration of STI
      services. CONCLUSIONS: The prevalence of cervical infections is relatively low in
      this population and the Ivorian algorithm that treats all women with vaginal
      discharge performs poorly. Over-treatment of cervicitis can be reduced by
      modifying the algorithm, although improved diagnostic tools are urgently needed
      to detect cervicitis in this population. Continued STI case management at the FP
      clinics is nevertheless justified because there exists an easily identifiable
      group of higher risk women who need STI care; and because of the demand by a
      large proportion of clients, the high prevalence of vaginal pathogens, and the
      limited costs to the FP programme.

PMID- 12791062
TI  - The relationship between age, sex, egg-count and specific antibody responses
      against Schistosoma mansoni antigens in a Ugandan fishing community.
AB  - In schistosomiasis endemic areas, antibody isotype responses against Schistosoma
      mansoni antigens vary with host age, sex and duration or intensity of infection,
      and are associated with susceptibility or resistance to infection. Identifying
      the quality and quantity of these responses is important to our understanding of
      the host-parasite relationship; however, the various host and parasite factors
      have a strong tendency to confound each other. We investigated the relationships
      and interactions between age, sex, faecal egg-counts and specific antibody
      isotype (IgA, IgG1, IgG2, IgG3, IgG4, IgE, IgM) responses to S. mansoni worm
      (SWA) and egg (SEA) antigens, amongst 380 individuals aged 5-59 from a fishing
      community from Uganda. This community was characterized by high levels of
      exposure, and high infection intensities, with higher infection intensities in
      males than in females. Multivariate anova was conducted with interaction terms
      between the three categorized explanatory variables. Most anti-SWA responses
      increased with age, whereas anti-SEA responses tended to decline with age,
      especially after puberty. IgG1-SWA, IgG4-SWA, IgG4-SEA, IgE-SWA responses
      increased with egg count, whereas IgG2-SEA decreased with egg count. IgG1-SWA,
      IgG4-SWA, IgE-SWA and IgG4-SEA responses were independently higher in males,
      whereas IgG2-SEA responses were independently higher in females. The significant
      effects of sex on isotype responses to adult worm antigens may be partly because
      of different levels of cumulative exposure. IgG4-SEA and IgG4-SWA were both
      strongly correlated with egg count. Patterns of IgE-SWA responses were
      qualitatively different to IgG4 responses, suggesting independent pathways of
      regulation.

PMID- 12791063
TI  - An improved, simple screening method for detection of glucose-6-phosphate
      dehydrogenase deficiency.
AB  - We established a new, simple and rapid screening method for detection of glucose
      6-phosphate dehydrogenase (G6PD)-deficiency by using a new formazan substrate, 2
      (2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium
      monosodium salt (WST-8) with a hydrogen carrier of 1-methoxyphenazine
      methosulfate (1-methoxy PMS), instead of a combination of 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and phenazine methosulfate
      (PMS), as used in many previous formazan methods. WST-8 does not react with
      haemoglobin, and the formed formazan is highly water-soluble, differing from MTT.
      Thus, the whole procedure can be performed in aqueous solution in a tube or well
      without any special equipment other than micropipettes. Within 1 h at room
      temperature, the strong orange colour of the WST-8 formazan formed in normal
      blood samples could be distinguished, by naked eye, from G6PD-deficient blood
      samples with less than 50% residual activity. We also found that reagents in the
      WST-8/1-methoxy PMS method were more resistant against exposure to sunlight than
      those in an MTT/PMS method. As the new method is both qualitative and
      quantitative, it is possible to express G6PD activity as increase of NADPH
      concentration by reading absorbance at 460 nm after incubation for 30 or 60 min.

PMID- 12791064
TI  - Prevalence of typhoid fever in febrile patients with symptoms clinically
      compatible with typhoid fever in Cameroon.
AB  - Typhoid fever is difficult to differentiate from other causes of infection such
      as malaria because their signs and symptoms often overlap. There has been an
      unprecedented increase in the number of typhoid fever cases diagnosed in
      Cameroon. Febrile patients are often treated for malaria and typhoid fever
      simultaneously. This cross-sectional study was carried out to determine the
      prevalence of typhoid fever in 200 consecutive patients with fever and symptoms
      clinically compatible with typhoid fever to verify recent estimates of a high
      prevalence of typhoid fever in Cameroon. Patients were enrolled in three of the
      10 provinces of Cameroon. Blood culture, thick and thin blood smears and Widal
      tests using acute sera were performed in all cases; stool culture for 120
      patients. Typhoid fever was confirmed in only 2.5% as evidenced either by culture
      (four cases) or high salmonella antibody titres (one case); malaria was diagnosed
      in 94 (47%) patients. Typhoid fever is not as endemic in Cameroon as recently
      feared.

PMID- 12791065
TI  - Cervical cancer screening: high coverage or high quality?

PMID- 12791067
TI  - Granulomatous infections in the transplant patient.

PMID- 12791068
TI  - Early results of targeted prophylaxis for coccidioidomycosis in patients
      undergoing orthotopic liver transplantation within an endemic area.
AB  - Coccidioidomycosis (CM) is an endemic fungal infection of the desert southwestern
      United States. In immunocompromised hosts, such as transplant recipients, this
      infection is often a severe, disseminated disease with high mortality. A history
      of coccidioidal infection or positive serologic results increases the risk of CM
      after transplantation. At our institution, all liver transplant candidates with
      either positive history or serologic results for coccidioidal infection receive
      fluconazole in order to prevent recurrent infection after transplantation.
      Patients with neither a history of coccidioidal infection nor positive serologic
      results do not receive prophylaxis but are followed serologically every 3 months.
      From June 1999 to October 2001, 81 liver transplantations were performed at our
      institution in 76 patients with end-stage liver disease. Four of these 76
      patients received prophylactic fluconazole in order to prevent CM. None of these
      4 patients had reactivation of CM. A new coccidioidal infection developed after
      orthotopic liver transplantation in 1 of 72 patients (1.4%). Close surveillance
      and targeted prophylaxis are safe and effective alternatives to universal
      prophylaxis for CM in patients undergoing liver transplantation in an endemic
      area.

PMID- 12791069
TI  - Mycobacterial infection after renal transplantation in a Western population.
AB  - Mycobacterial infection is a serious opportunistic infection in renal transplant
      recipients. The incidence is higher in developing than in developed Western
      countries. This study is a single-centre retrospective review of the records of
      2502 renal transplant recipients in Belgium. Fourteen cases of mycobacterial
      infection (9 Mycobacterium tuberculosis and 5 atypical mycobacterial infection)
      were diagnosed. The time interval between transplantation and diagnosis was 64 +/
      80 months (mean +/- SD, range 5-188) for M. tuberculosis and 92 +/- 75 months
      (range 14-209) for atypical mycobacterial infection. The localisation of M.
      tuberculosis was pulmonary/pleural in 67% and extrapulmonary in 33%. The atypical
      mycobacterial infections were located in skin, tendons, and joints. Eight
      patients received IV prednisolone pulse therapy for acute rejection long before
      the time of mycobacterial infection. The initial antimycobacterial therapy
      consisted of a combination of isoniazid, rifampicin, and ethambutol in all
      patients. In patients with M. tuberculosis infection, a good response to
      antimycobacterial therapy was obtained. In patients with atypical mycobacterial
      infection, initial treatment was successful in 3 out of 5 patients, in 1 patient
      recurrence was diagnosed and in another patient, who is still under treatment at
      present, the initial treatment was adjusted after identification of the atypical
      mycobacterium and its antibiogram. The incidence of mycobacterial infection after
      renal transplantation did not increase with newer immunosuppressive therapy. The
      major risk factor is the total dose of corticosteroids. All patients responded
      well without major reductions in immunosuppressive therapy. Chemoprophylaxis for
      high-risk patients still is recommended.

PMID- 12791070
TI  - Systemic nocardiosis following allogeneic bone marrow transplantation.
AB  - Five cases of systemic Nocardia infection were diagnosed among 301 allogeneic
      bone marrow transplant recipients. A sixth case included in this report received
      her transplant at another institution. The cumulative annual incidence rate of
      this infection was 1.75%. All patients had been treated previously for acute
      graft-versus-host disease (GVHD). At the time of diagnosis of systemic Nocardia
      infection, a median of 198 (range 148-1121) days after transplantation, all
      patients had extensive chronic GVHD and were taking 2 to 3 immunosuppressive
      medications. Prior to diagnosis of Nocardia infection patients had experienced
      multiple opportunistic infections, including infections with Mycobacterium avium
      intracellulare, Pneumocystis carinii, and cytomegalovirus antigenemia. Treatment
      with trimethoprim-sulfamethoxazole (TMP-SMX), ceftriaxone, or carbapenem
      antibiotics resulted in a median survival of 219 days from the time of diagnosis
      and an actuarial 1-year survival of 40%. All patients who received more than 2
      weeks of therapy were cured of their infections. Notably, 5/6 patients in this
      cohort were unable to take TMP-SMX because of myelosuppression. In comparison
      with randomly selected control patients, the use of pentamidine for prevention of
      P. carinii infection was associated with a marginal increase in the risk of
      Nocardia infection. We postulate that the use of TMP-SMX may be of benefit in the
      prophylaxis of infections other than P. carinii in patients with chronic GVHD.

PMID- 12791072
TI  - Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens
      in transplant recipients: in vitro effect of r-metHuG-CSF (Filgrastim).
AB  - Phagocyte respiratory burst capacity in response to pathogenic fungi and the in
      vitro effects of granulocyte colony-stimulating factor (G-CSF) were examined in
      15 normal volunteers and 39 transplant recipients (4 autologous and 4 allogeneic
      bone marrow, 3 heart, 10 liver, 8 lung, and 10 kidney). Chemiluminescence was
      measured for reaction mixtures of diluted whole blood, opsonized fungi, and
      luminol, with and without in vitro incubation with r-metHuG-CSF (Filgrastim).
      Transplant patients exhibited significantly impaired respiratory burst responses
      to conidia and yeast compared with controls, but this was reversed with
      Filgrastim. Responses to hyphae were low for both groups, and G-CSF had little or
      no effect. There was excellent correlation between responses to fungi and
      responses to opsonized zymosan. In vitro respiratory burst capacity is impaired
      in transplant recipients. This may predict susceptibility to invasive fungal
      infections. G-CSF can reverse impaired phagocyte function and is of potential
      benefit in the prevention and/or treatment of fungal infection in transplant
      patients.

PMID- 12791071
TI  - Polyomavirus in kidney and kidney-pancreas transplant recipients.
AB  - PURPOSE: To report the incidence and clinical characteristics of polyomavirus
      (PV) nephritis in kidney (KTX) and kidney-pancreas transplant (KPTX) recipients.
      METHODS: Single center retrospective analysis of all cases of PV nephritis in KTX
      and KPTX patients transplanted between 1994 and 1999. RESULTS: Thirteen (5 KTX
      and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n =
      22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was
      higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after
      KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in
      diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to
      diagnosis of PV nephritis was 18 (range 6-48) months after KTX and 17 (range 9
      31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin
      inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in
      immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three
      patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a
      reduction in immunosuppression. Despite multiple antiviral treatment regimens,
      renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX
      patients. All KPTX patients remain insulin independent and 2 were successfully
      retransplanted with living donor kidneys. 2 patients (15%) died but there was no
      mortality directly related to the virus. CONCLUSIONS: Polyomavirus nephritis may
      be increasing in incidence and appears to be unresponsive to either conventional
      antiviral agents or a reduction in immunosuppression. Most of our cases occurred
      in male diabetic patients undergoing cadaveric donor transplantation and were
      preceded by biopsy-proven nephrotoxicity. Further studies are needed to better
      define the pathogenesis of PV and effective antiviral treatment.

PMID- 12791073
TI  - T-lymphocyte development and models of thymopoietic reconstitution.
AB  - T-cell development occurs in the thymus and involves a complex stepwise
      differentiation process from hematopoietic progenitor cell through to the
      emergence of positively selected, non-self reactive naive T cells, which emigrate
      from the organ into the blood stream. This process takes place in the three
      dimensional context of a delicate latticework of thymic stromal cells, including
      epithelial-derived cells and dendritic cells that assist in the development of
      the mature T cell. The details of the steps in T-cell development are now more
      comprehensively understood and furthermore in vitro systems are in development to
      reiterate this process in vitro. The clinical impact of this work is clearly the
      understanding of immune reconstitution in immune compromised patients (e.g.,
      those with HIV/AIDS or post transplantation) and the development of novel
      techniques for regenerating the spectrum of T-cell function in these individuals.

PMID- 12791074
TI  - Cavitary pneumonia due to Rhodococcus equi in a heart transplant recipient.
AB  - Rhodococcus equi is an uncommon human pathogen that usually affects
      immunocompromised patients. We present a case of a 68-year-old male heart
      transplant recipient, who developed rhodococcal pneumonia with secondary
      bacteremia 10 months post-transplant. The patient was a retired carpenter who was
      involved in breeding of horses. He responded completely to the treatment with
      vancomycin and imipenem/cilastin, followed by oral ciprofloxacin and minocycline
      for total treatment duration of 5 months. This case highlights the association
      between an animal exposure and infection with a unique opportunistic pathogen.

PMID- 12791075
TI  - Fever, hepatosplenomegaly, and pancytopenia in a renal transplant recipient.

PMID- 12791076
TI  - Multidrug-resistant Corynebacterium striatum pneumonia in a heart transplant
      recipient.
AB  - Corynebacterium striatum is a rare, but likely underreported, cause of serious
      infections in immunocompromised hosts and generally is susceptible to multiple
      classes of antimicrobial agents. Here we report the first case of C. striatum
      infection in a solid organ transplant recipient. Three years after heart
      transplantation, a 58-year-old man developed bilateral pneumonia and pulmonary
      embolism. He did not improve with levofloxacin, piperacillin/tazobactam, and
      heparin treatment. A homogeneous population of abundant gram-positive rods was
      repeatedly demonstrated in sputum and bronchoalveolar lavage fluid, and C.
      striatum was grown in pure culture. The isolate was unusual for its multidrug
      resistant (MDR) antimicrobial susceptibility pattern. The pneumonia resolved with
      4 weeks of vancomycin therapy, in combination with rifampin given only during the
      first 2 weeks of treatment. The isolation of coryneforms ("diphtheroids") is
      often attributed to contamination. Their abundant presence on direct examination
      of specimens and/or their growth in pure culture suggest a pathogenic role,
      however, and indicate the need for accurate microbiological identification,
      particularly in immunocompromised hosts who have been hospitalized and previously
      treated with antibiotics. Combination therapy that includes vancomycin may be the
      most prudent treatment for MDR C. striatum infections.

PMID- 12791077
TI  - Burkholderia urinary tract infection after renal transplantation.
AB  - Urinary tract infection is a common complication after renal transplantation. The
      etiologies are diverse and the bacterial agents may sometimes be acquired during
      the hospital stay. We report a patient who developed Burkholderia cepacia urinary
      tract infection after renal transplantation. The bacteria showed in vivo
      resistance to all of the available antibiotics. A graft nephrectomy was
      eventually required to clear the infection. The consequence of some fastidious
      infection may be catastrophic and early recognition and treatment is necessary to
      optimize the treatment.

PMID- 12791078
TI  - Survey of the implementation of the recommendations in the Health Services
      Circular 1998/224 'Better Blood Transfusion'.
AB  - This report describes a questionnaire survey on the implementation of the
      recommendations of the Health Services Circular (HSC) 'Better Blood Transfusion'
      1998/224 for improving transfusion practice. The survey was carried out to inform
      a second UK Chief Medical Officers' symposium on 'Better Blood Transfusion' in
      October 2001. Sixty-nine percent of hospitals where blood is transfused in
      England participated. The results show that, by 2001, most hospitals had
      established Hospital Transfusion Committees (HTCs), developed protocols for the
      process of transfusion and were participating in the Serious Hazards of
      Transfusion (SHOT) scheme. However, there was limited compliance with other
      recommendations, including the provision of training for staff involved in
      transfusion and information to patients, the development of protocols for the
      appropriate use of blood, the performance of audits of transfusion practice and
      the introduction of peri-operative cell salvage. The survey did not determine the
      reasons for this limited compliance. New initiatives including the issue of a
      further HSC on 'Better Blood Transfusion' are aimed at enabling hospitals to
      improve their transfusion practice in a more systematic way than that was found
      in the results of this survey.

PMID- 12791079
TI  - Tracing blood units to their recipients: results of a two-centre study.
AB  - An important principle of the use of blood components is the ability to trace
      them from the donor to the recipient. This study set out to establish whether
      there was sufficient documentation in patient case notes to confirm the
      transfusion of blood components in a sample of computer blood bank records at two
      large teaching hospitals in UK. The criteria for verification of transfusion were
      taken from guidelines from the British Committee for Standards in Haematology
      (Transfusion Medicine 1999, 9, 227-238). The blood bank computer records
      indicated that 486 units of blood components were issued and not returned to the
      blood bank for 80 patients during a 2-month period. Of the 486 units, transfusion
      of 409 units (84%) was verified against patient notes, but 77 units (16%) could
      not be verified as received by the patient. The study showed that documentation
      of transfusions was variable. For example, written prescriptions were only found
      for 204 units (42%). These results have implications for 'lookback studies'
      involving blood transfusion. Further efforts are required to educate those
      involved in transfusing blood about the need for accurate documentation.

PMID- 12791080
TI  - Remuneration for blood donation and attitudes towards blood donation and receipt
      in Leeds.
AB  - In a survey of attitudes towards remuneration for blood donation in Leeds, the
      following questions were completed by 489 adults (N), of whom 89 were regular
      donors, 105 were lapsed donors and 295 had never donated: 'If you needed blood,
      would you be content if the donor had been paid: yes/no'. 'If I were paid enough
      I would be less/equally/more likely to donate blood '. The majority (67.7%) of
      potential recipients would be content if the donor had been paid. The prospect of
      remuneration made 16.4% of respondents more likely and 14.5% less likely to
      donate. As the difference is less than 2% of N, offering remuneration may not
      lead to a significant increase in the number of donations. A statistical
      comparison (chi2 = 45, d.f. = 2, P << 0.001) showed associations between the
      responses 'more likely to donate if paid' and 'content to receive blood from a
      paid donor', and between the responses 'less likely to donate if paid' and 'not
      content to receive blood from a paid donor'. Age distributions are presented for
      the donor status categories and the responses to the main questions. Of 129
      people who stated a minimum, nonzero payment that would persuade them to donate,
      103 (80%) suggested pound sterling 10 or less.

PMID- 12791081
TI  - Possible mechanisms underlying development of transfusion-related acute lung
      injury: roles of anti-major histocompatibility complex class II DR antibody.
AB  - Anti-major histocompatibility complex (anti-MHC) antibodies (Abs) and
      antipolymorphonuclear neutrophil (anti-PMN) Abs are generally considered as the
      main causes of the development of transfusion-related acute lung injury (TRALI),
      which is one of the most severe and sometimes lethal side effects of transfusion.
      These Abs are postulated to activate recipient's leucocytes, resulting in the
      release of soluble factors such as reactive oxygen species and detrimental
      cytokines and chemokines. The harmful effects on the lung tissues and resident
      leucocytes of these malignant factors are suspected to be profoundly involved in
      TRALI reactions. Several reports have indicated the principle effect of
      biologically active lipids on the pathogenesis of TRALI. However, the precise
      mechanisms of TRALI development remain unclear. To resolve this issue, we have
      been investigating cytokines that induce continuous inflammation of the lungs,
      specifically focusing on the cytokines derived from activated PMNs. We observed
      that the granulocyte-macrophage colony-stimulating factor (GM-CSF) markedly
      enhances the expression of MHC class II DR in PMNs. Moreover, MHC class II DR
      expressing PMNs were also proved to express a high-affinity receptor for
      immunoglobulin E (IgE) (FcepsilonRI) and to produce tumour necrosis factor-alpha,
      interferon-gamma and interleukin-18 following a challenge with an anti-MHC class
      II DR monoclonal Ab (MoAb) or anti-DR antiserum. It is strongly suggested that
      amongst various inflammatory mediators, at least these three cytokines may
      contribute to the duration of inflammatory reactions in the lungs. Furthermore,
      FcepsilonRI expression, in GM-CSF-treated PMNs, suggests the involvement of PMNs
      in IgE-mediated immune reactions.

PMID- 12791082
TI  - Human neutrophil antigen-4a gene frequencies in an Australian population,
      determined by a new polymerase chain reaction method using sequence-specific
      primers.
AB  - Human neutrophil antigen-4a (HNA-4a) is a high-frequency (99% in the USA)
      neutrophil antigen, which has recently been linked to a case of alloimmune
      neonatal neutropenia. We have devised a new polymerase chain reaction sequence
      specific primer (PCR-SSP) method to assess HNA-4a genotype, and used it to
      determine the HNA-4a gene frequencies in an Australian population. The gene
      frequency was found to be 0.906, which is the same as in the American population.
      The PCR-SSP genotyping method perfectly correlates with serological phenotyping
      and is efficient for screening large numbers of samples.

PMID- 12791083
TI  - Competitive enzyme-linked immunoassay of monoclonal immunoglobulin G anti-D
      preparations.
AB  - The development of monoclonal immunoglobulin G (IgG) anti-D for prophylaxis
      necessitates estimation of their potency in terms of their red cell-binding
      ability, but it is unclear which quantification methodology is most suitable for
      this. The aim of this study was to assess 50 monoclonal anti-D from the 4th
      International Workshop for quantitative and qualitative binding to red cells in a
      competitive enzyme-linked immunoassay (EIA) in which varying amounts of
      monoclonal antibodies (MoAbs) and a constant amount of biotinylated monoclonal
      anti-D (BRAD-5) compete for red cell binding. The potencies of the MoAb were
      estimated against the International Reference Preparation (IRP) for anti-D Ig.
      Two MoAbs as supplied were insufficiently inhibitory of biotinylated BRAD-5
      binding to be quantified; the potencies of the remainder ranged from 4 to 343 IU
      mL-1 and included 11 MoAbs showing dose-responses that were nonparallel to those
      of other MoAb and the IRP. Estimation of the concentration of antibody in the
      supernatants by radial immunodiffusion ranged from 0.5 to 61 micro g mL-1, giving
      specific activities of <1-24 IU micro g-1. The results show that competitive EIA
      is suitable for quantitating most monoclonal anti-D for development and quality
      control purposes, regardless of their D epitope reactivity.

PMID- 12791084
TI  - The first example of anti-Diego(b) found in a Polish woman with the Di(a+b-)
      phenotype and haemolytic disease of the newborn not requiring treatment.
AB  - All pregnant women with anti-Diegob (anti-Dib) described so far were non
      Caucasians. We present the case of a Polish Di(a+b-) woman with anti-Dib, which
      did not bind complement, was immunoglobulin G3 (IgG3) alone and had very low
      functional activity. She delivered a Di(a+b+) infant with a positive direct
      antiglobulin test and the antibody in his serum but very mild haemolytic disease.
      Both parents of the pregnant woman were Di(a+b+), so were all her three children.
      The whole family have been living in a small village in southeastern Poland for a
      long time. The rare Diego phenotypes, found now and previously in Poland, suggest
      gene admixture introduced as a result of Poland being invaded by Mongolian
      background Tatars during the past centuries.

PMID- 12791085
TI  - Myocardial ischaemia precipitated by acute normovolaemic haemodilution.
AB  - Acute normovolaemic haemodilution (ANH) is widely used as part of a blood
      conservation strategy to minimize the use of allogenic blood in the peri
      operative period. Its role has not been proven in a prospective randomized trial.
      The potential benefits must not blind clinicians to the possible hazards. We
      report a life-threatening complication of ANH prior to induction of anaesthesia
      for aortic aneurysm repair.

PMID- 12791086
TI  - The impact of screening a platelet donor panel for human leucocyte antigen
      antibodies to reduce the risk of transfusion-related acute lung injury.

PMID- 12791087
TI  - Was it there all the time?
AB  - The complement system is old, yet it may still have something new to teach us.
      For many years, research has existed which shows that C3d, in addition to its
      established role as an adjuvant, could have an immunosuppressive activity. Being
      true, it suggests that a common mechanism may be used both by organisms and by
      their pathogens to prevent unwanted immune responses.

PMID- 12791088
TI  - Expression and modulation of the human immunoglobulin A Fc receptor (CD89) and
      the FcR gamma chain on myeloid cells in blood and tissue.
AB  - CD89, the human immunoglobulin A (IgA) Fc receptor (FcR), is a potential target
      for antibody-based therapeutics, but little is known about its expression and
      modulation in vivo. In this study, we examined the expression pattern of CD89 and
      its signalling subunit, the FcR gamma chain, on circulating myeloid cells and in
      various tissues. Our results showed a wide tissue distribution of CD89+ cells.
      Thus, CD89+ cells were evident as clusters in tonsils and appendix and scattered
      in varying numbers in lymph nodes, kidney, liver, intestinal mucosa,
      bronchoalveolar lavage and peritoneal fluid. Most CD89+ cells were identified as
      neutrophils with high levels of CD89. A few recently emigrated macrophages
      (CD14low), weakly positive for CD89, were occasionally found in the tissues and
      more often in the peritoneal fluid. The level of CD89 on neutrophils in tissues
      and peripheral blood was similar, whereas on monocytes it was much lower in the
      tissues than in blood, and it was absent on CD14-/CD68+ intestinal lamina propria
      macrophages. Conversely, we detected much higher levels of the FcR gamma chain in
      monocytes than in neutrophils, but the FcR gamma chain was also downregulated in
      tissue macrophages as well as in in vitro-differentiated monocyte-derived
      macrophages and dendritic cells. The implications of our current findings on the
      biological functioning of CD89 are discussed.

PMID- 12791089
TI  - Affinity and epitope profiling of mouse anti-CD40 monoclonal antibodies.
AB  - The CD40-CD40L interaction plays a critical role in both humoral and cellular
      immune responses and interfering antibodies have been suggested as an effective
      approach for the treatment of lymphomas and autoimmune diseases. In this study we
      have profiled a panel of mouse antihuman CD40 monoclonal antibodies (MoAbs),
      regarding their CD40 binding affinity and epitope-specificity relative to the
      CD40L binding in relation to their cellular activating potential. Despite a
      rather similar domain-recognition profile, the MoAbs blocked the CD40L binding to
      a varying degree, with MoAb 5C3 being the poorest inhibitor. There was no
      correlation between affinity and cellular activation potential. In contrast, a
      correlation between the ability to block CD40L-binding and activation potential
      could be seen. We believe that this analysis of several mouse anti-CD40
      antibodies can be used to develop strategies for producing new human anti-CD40
      antibodies that can more effectively induce or block B-cell proliferation.

PMID- 12791090
TI  - The use of fluorometric assays to assess the immune response to DNA in murine
      systemic lupus erythematosus.
AB  - Antibodies to DNA (anti-DNA) play an important role in the pathogenesis of
      systemic lupus erythematosus (SLE). In blood, these antibodies may exist in a
      free, unbound state or as part of complexes with DNA. Furthermore, circulating
      DNA may be either complexed or free. Because of the central role of these
      immunoreactants (anti-DNA and DNA) in the disease, monitoring of their levels
      could provide valuable information for both clinical and investigative purposes.
      In these studies, we have explored the use of a DNA-binding dye, PicoGreen, for
      the detection of circulating DNA, either total or immune complex bound. In
      addition, we have used this dye for Farr-type antibody assays. Using autoimmune
      MRL/lpr mice as a model, we have shown that, while the levels of free DNA in the
      plasma of these mice were comparable with those of normal BALB/c mice, the
      amounts in complexes precipitable by ammonium sulfate were significantly greater.
      Furthermore, we showed that Farr assays using PicoGreen reliably detect levels of
      free anti-DNA, with values correlated with anti-DNA levels by an enzyme-linked
      immunosorbent assay. Together, our results suggest that a fluorometric dye can
      accurately monitor DNA and anti-DNA antibody levels in SLE and may provide
      important information on immunopathogenesis.

PMID- 12791091
TI  - Liver metastasis of cancer facilitated by chemokine receptor CCR6.
AB  - When injected subcutaneously, mouse plasmacytoma (MOPC315) grew rapidly in situ,
      and metastatic cells became detectable first in the lymph nodes (LNs) and bone
      marrow, and later in the liver and lungs. We studied MOPC315 cell migration by
      tracking metastatic cells labelled with green fluorescent protein (GFP). We
      measured the levels of their chemokine receptor mRNA (by semiquantitative and
      real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR),
      because chemokines can regulate organ predilection of metastasis. Freshly sorted
      metastatic cells and tumour cell lines derived from the liver of BALB/c mice
      overexpressed functional CCR6 and CCR7 molecules compared with primary tumour.
      Preincubation with the CCR6 ligand (CCL20) induced liver-sorted tumour cells to
      preferentially colonize the liver, demonstrating an association between liver
      metastasis and CCR6 expression in the mouse. Because the liver is a common site
      for metastasis, second only to draining LNs, we wished to ascertain whether this
      finding could be generalized, i.e. whether other cancers can use the similar
      mechanism of metastasis to the liver, and whether it holds true for humans. We
      found that CCR6 is overexpressed in small liver metastases of colon, thyroid and
      ovarian carcinomas compared with normal liver. Because human liver constitutively
      expresses CCL20, it could attract and select CCR6+ cancer cells. We suggest that
      chemotaxis via CCR6 might be a common mechanism by which malignant cancers
      metastasize to the liver. As metastasis in patients with cancer poses the biggest
      peril for survival, inhibition of CCR6 signalling, either during or after medical
      or surgical treatment, might be useful in preventing liver metastasis.

PMID- 12791092
TI  - Follicular lymphoma cell lines, an in vitro model for antigenic selection and
      cytokine-mediated growth regulation of germinal centre B cells.
AB  - In the periphery, B cells differentiate in germinal centres (GCs) of secondary
      lymphoid organs. Isolated GC cells die quickly in vitro by apoptosis. Therefore,
      cell lines originating from follicular lymphomas, which are the malignant
      counterparts of GC B cells, would provide a stable in vitro model to study the
      immunobiology of GC B cells. We have established three novel human follicular
      lymphoma cell lines that were characterized with special reference to
      immunophenotypic features, response to B-cell receptor (BCR) triggering, response
      to cytokines and cytokine mRNA expression. One of the cell lines, HF-1A3, has a
      phenotype of a centrocyte. It expresses surface immunoglobulin G (sIgG) and dies
      by apoptosis following BCR cross-linking. Co-stimulation with interleukin-6 (IL
      6), IL-15 or interferon-gamma (IFN-gamma) rescues HF-1A3 cells from BCR-induced
      apoptosis. The second cell line, HF-28, also represents phenotypically an IgG+
      centrocyte. Ligation of its BCR leads to the cell-cycle arrest at G1 instead of
      apoptosis. HF-28 cells express both CD45RA and RO isoforms, which is unusual in B
      lymphocytes apart from plasma cells, thus suggesting a transition to plasma cell
      phenotype. The third cell line, HF-4.9, which phenotypically represents an sIgM+
      centroblast, responds by proliferation to BCR cross-linking. These cell lines
      offer a unique in vitro model to study antigenic selection and cytokine-mediated
      growth regulation of human GC B cells.

PMID- 12791093
TI  - On the site of C4 deposition upon complement activation via the mannan-binding
      lectin pathway or the classical pathway.
AB  - The mannan-binding lectin (MBL) pathway and the classical pathway of complement
      activation are initiated by the binding of the recognition structure of the
      initiator complexes, MBL and C1q, respectively, to their ligands, i.e.
      carbohydrate structures or immune complexes. Proenzymes associated with MBL or
      C1q are then activated and generate C3 convertase through the activation of C4
      and C2. The cleavage product of C4, C4b, attaches covalently to nearby hydroxyl
      or amino groups. The current picture is that C2 must then attach to C4b before
      being cleaved by the same associated proteases into the enzymatically active
      fragment, C2b. This suggests a stringent requirement for the deposition of C4b
      very close to the initiator complex, or indeed onto the initiator complex. We
      examined the possibility of C4b being bound to the initiator complex by a solid
      phase assay, allowing for the selective elution of the initiator complexes,
      followed by quantification of the C4b being eluted and the C4b remaining on the
      solid phase. Also, we estimated the generation of complexes between the released
      initiator complex and C4b. More than 99% of deposited C4b was bound directly to
      the solid phase rather than to the initiator complex. Our approach cannot answer
      the question of the whereabouts of the C2 when it is cleaved.

PMID- 12791094
TI  - Less sensitivity for late airway inflammation in males than females in BALB/c
      mice.
AB  - Several studies have investigated allergic airway inflammation, a T helper 2
      (Th2)-type immune response, using a mouse model of asthma. At present, however,
      no reports have described sex differences in the sensitivity of late airway
      inflammation (LAI). The LAI induced by ovalbumin in adult BALB/c mice was
      compared in males and females or sham-operated males and castrated males. The
      males showed less severe bronchial-bronchiolar inflammation with infiltration of
      eosinophils and lymphocytes and lower content of such cells in bronchoalveolar
      fluid than the females. Moreover, interleukin-4 (IL-4) mRNA expression levels in
      splenic cells were lower in the males than in the females. Castrated males
      performed like the females. Moreover, when compared with the sham-operated males,
      the castrated males showed lower testosterone levels in the blood. The present
      results suggest that less sensitivity for LAI in the males may be because of the
      decreased Th2 cell responses compared with the females. Moreover the
      testosterone, at least in part, may be responsible for the decreased Th2 cell
      responses in males in vivo.

PMID- 12791095
TI  - Increased expression of soluble cytotoxic T-lymphocyte-associated antigen-4
      molecule in patients with systemic lupus erythematosus.
AB  - A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) was
      recently found and shown to possess a downregulatory function as a membrane-bound
      CTLA-4 molecule. The purpose of the study was to investigate the expression of
      sCTLA-4 molecule in patients with systemic lupus erythematosus (SLE). One hundred
      patients with SLE and 40 age- and sex-matched healthy individuals were enrolled
      in the study. The results showed that patients with SLE have significantly higher
      levels of sCTLA-4 in sera than healthy controls (21.6 +/- 12.3 ng/ml versus 5.9
      +/- 5.4 ng/ml, P < 0.001). Increased expression of sCTLA-4 mRNA in peripheral
      blood mononuclear cells (PBMCs) was also found in SLE patients. However, we could
      not find a statistically significant correlation between the serum levels of
      sCTLA-4 and lupus disease activities. The reported CTLA-4 gene polymorphism in
      promoter region at position -318 did not affect the levels of sCTLA-4. To the
      best of our knowledge, this is the first report showing that patients with SLE
      have increased sCTLA-4 expression. However, the mechanism and role of increased
      sCTLA-4 in the pathogenesis of SLE remains elucidated.

PMID- 12791096
TI  - Egg yolk anti-BfpA antibodies as a tool for recognizing and identifying
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major aetiological agent of
      childhood diarrhoea in developing countries. The structural repeating protein A
      subunit, BfpA, found in the bundle-forming pilus, is one of the virulent factors
      for EPEC pathogenesis. Recombinant BfpA in laying hens elicited sustained and
      vigorous antibody production. Immunoglobulin Y (IgY) anti-BfpA antibodies were
      recovered from egg yolk, purified and characterized. Immunoadsorption with whole
      extracts of the isogenic E. coli EPEC adherence factor (EAF) strain that lacks
      BfpA rendered the resulting IgY preparations capable of: (a) recognizing purified
      or recombinant BfpA proteins in a dose-dependent fashion; (b) blocking the
      colonization of HeLa cells by EPEC EAF+, in vitro; (c) specifically identifying
      E. coli bearing EAF+; and (d) inhibiting the growth of E. coli EAF+ but not the
      EAF strain. IgY anti-BfpA is potentially useful as a specific, low-cost
      immunobiological reagent to screen human faecal specimens for the presence of
      EPEC.

PMID- 12791097
TI  - Probing the specificity of human myeloma proteins with a random peptide phage
      library.
AB  - Human myeloma proteins (HMPs) from 10 patients with multiple myeloma (MM) were
      used to affinity-select peptides from a random phage-display peptide library.
      Binding peptides were identified for the 10 analysed antibodies (eight,
      immunoglobulin G (IgG), and two, immunoglobulin A (IgA)). The specificity of the
      binding was confirmed by competitive experiments using phages and chemically
      synthesized peptides. Interestingly, some phage-displayed peptides were immuno
      selected with HMPs isolated from different patients. Sequence alignments and
      homology searches revealed a significant homology with human proteins (e.g.
      neural cell adhesion proteins) and pathogen-derived proteins (e.g. herpes simplex
      virus capsid proteins). The selected peptides could be useful as targeting agents
      for myeloma cells expressing surface immunoglobulins.

PMID- 12791098
TI  - Cytokines affect resistance of human renal tumour cells to complement-mediated
      injury.
AB  - Overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour
      cells may hamper the effect of immunotherapy with complement-activating
      monoclonal antibody (MoAb). Therefore, it is important to investigate whether
      cytokines can downregulate the expression of mCRP on tumour cells. In this study,
      the effect of 10 cytokines on the expression of the mCRP CD46, CD55 and CD59 and
      the renal tumour-associated antigen G250/MN/CAIX on four human renal tumour cell
      lines and proximal tubular epithelial cells was determined by flow cytometry. In
      addition, it was measured whether changes in the expression of the classical
      pathway regulatory proteins CD55 and CD59 had an effect on C3 deposition and
      lysis. Interleukin-1beta (IL-1beta) consistently downregulated the expression of
      CD46 and CD59; IL-4 consistently downregulated the expression of CD46 and
      transforming growth factor-beta1, consistently downregulated the expression of
      both CD46 and CD55. However, treatment with IL-1beta and IL-4 also decreased the
      expression of G250/MN/CAIX. Changes in the expression of CD55 and CD59 were
      associated with changes in the amount of C3 deposited and the extent of
      complement-mediated lysis, respectively. This suggests that clinical
      immunotherapy, consisting of treatment with cytokines and MoAb, may induce either
      up- or downregulation of CD55 or CD59 and thus affect the effectiveness of
      immunotherapy with MoAb.

PMID- 12791099
TI  - Restoration of human immunodeficiency virus-1-specific responses in patients
      changing from protease to non-nucleoside reverse transcriptase inhibitor-based
      antiretroviral therapy.
AB  - The effect of altering antiretroviral therapy (ART) on responses to viral, recall
      and human immunodeficiency virus (HIV)-1-specific recombinant antigens and
      interleukin-2 (IL-2) in HIV-1-infected patients was assessed. A longitudinal
      cohort study in eight HIV-1 infected individuals following a clinically indicated
      therapy change (seven for drug intolerance and one for virological failure) from
      protease inhibitor (PI) to non-nucleoside reverse transcriptase inhibitor (NNRTI)
      based antiretroviral regimens was performed. CD4 T-cell counts, viral loads,
      lymphoproliferative responses, cytokine production and latent proviral
      deoxyribonucleic acid (DNA) were measured at baseline and at weeks 12 and 24
      after therapy substitution. Following therapy-switch there was a 33% proportional
      increase in mitogen response (95% confidence interval (CI), 3-33%) and a 31%
      increase (95% CI, 15-48%) in viral and recall-antigen responses. Six patients
      developed proliferative responses to low concentration IL-2 stimulation. All
      patients demonstrated an increase in median HIV-1-specific responses, as three
      had detectable virus at baseline (two being viral rebound); this may reflect an
      autovaccination effect. Proviral DNA changes largely reflected plasma HIV-1
      ribonucleic acid (RNA). In conclusion, NNRTI substitution for a PI may favour
      immune reconstitution with an improvement in HIV-1-specific responses, which may
      reflect differential effects on antigen processing and presentation, an
      autovaccination effect or alternatively a potential suppressive effect of the PI.

PMID- 12791100
TI  - Prospect for an Entamoeba histolytica Gal-lectin-based vaccine.
AB  - Entamoeba histolytica is the aetiological agent of invasive amoebiasis, the third
      leading parasitic cause of mortality in the world. The disease can be easily
      cured by chemotherapy; however, prevention, mainly in the form of vaccination,
      could greatly decrease the incidence of the disease, and possibly help in its
      eradication. The parasite's surface galactose and N-acetyl-d-galactosamine
      inhibitable adherence lectin (Gal-lectin) is highly antigenic and is the most
      promising subunit vaccine candidate. We have generated a Gal-lectin-based DNA
      vaccine and tested its immunogenicity in mice. Although further optimization will
      probably be required, this vaccine could help in the generation of an amoebiasis
      DNA vaccine for use in humans.

PMID- 12791101
TI  - Abomasal lymph node responses to Haemonchus contortus intestinal antigens
      established in kid goats by infection or immunization with intestinal antigens.
AB  - Immune responses to Haemonchus contortus intestinal antigens were evaluated using
      abomasal lymph node (ALN) lymphocytes from kid goats protected against challenge
      infection by immunization with parasite intestinal antigen, and from kids that
      were challenged after immunization with ovalbumin. ALN lymphocytes from the
      intestinal antigen-immunized group produced significantly higher antibody levels
      against intestinal antigens than the ovalbumin group, supporting the theory that
      immunization contributed to that ALN response. In contrast, intestinal lysates
      and membrane enriched preparations from intestinal cells stimulated significant
      proliferation of ALN lymphocytes in both groups. The proliferation was antigen
      dependent, since intestinal antigens failed to stimulate proliferation in ALN
      lymphocytes from unimmunized and uninfected kids. For both the intestinal antigen
      and ovalbumin immunized groups, CD4+ T lymphocytes predominated in ALN
      lymphocytes that were stimulated to proliferate by intestinal antigens. The
      results indicate that H. contortus infection alone can induce ALN lymphocyte
      responses to intestinal antigens. In contrast to ALN lymphocyte responses, serum
      antibody against intestinal antigens was generally low to undetectable in
      ovalbumin-immunized kids following infection. Abomasal mucus from an H. contortus
      infected lamb was probed with a monoclonal antibody that binds to a periodate
      sensitive determinant on numerous H. contortus intestinal membrane and secreted
      proteins. Numerous bands of reactivity were detected, indicating that multiple
      parasite intestinal antigens were released into abomasal mucus during infection.
      The results, challenge the general concept that H. contortus intestinal antigens
      are 'hidden' from the host immune system during an infection. On the contrary,
      parasite intestinal proteins may be relatively abundant antigens presented to the
      host during infection. In addition, ALN T lymphocytes appear to provide a more
      sensitive measure than serum antibody to detect presentation of these antigens to
      the host immune system.

PMID- 12791102
TI  - Characterization of a recombinant immunomodulatory protein from the salivary
      glands of Dermacentor andersoni.
AB  - The gene encoding a 36-kDa (p36) immunomodulatory protein present in saliva of
      Dermacentor andersoni was cloned in prokaryotic and eukaryotic expression
      vectors. A polymerase chain reaction (PCR)-generated cDNA lacking signal peptide
      was cloned into the Escherichia coli expression vector pET28 and a similar
      sequence was cloned into pIB/V5-His-TOPO expression vector for stable
      transfection of insect cells, High 5 trade mark. The 26-kDa molecular mass of p36
      expressed by bacteria is in agreement with that predicted from the translated
      full-length cDNA sequence. Eukaryotic-cell-expressed p36 consisted of multiple
      forms with molecular masses between 34 and 36 kDa. These multiple forms were
      attributed to differences in post-translational modifications. N-linked mannose
      was detected on insect-cell-expressed and tick-derived p36. Multiple bands
      remained after endoglycosidase removal of N-linked sugars, indicating the
      presence of other modifications. Both bacterial- and insect-cell-expressed p36
      reacted on immunoblots with polyclonal antibodies raised against tick-derived
      p36. Insect-cell-expressed p36 suppressed T-lymphocyte-mitogen-driven in vitro
      proliferation of splenocytes from tick-naive mice in a dose-dependent manner.
      Bacterial-cell-expressed p36 lacked immunomodulatory activity.

PMID- 12791103
TI  - Characterization of a 35-kDa carbohydrate larval antigen (CarLA) from
      Trichostrongylus colubriformis; a potential target for host immunity.
AB  - In an accompanying paper we show that antibodies in intestinal mucus that
      recognize a 35-kDa antigen from the surface of the L3 stage of the sheep
      intestinal nematode parasite, Trichostrongylus colubriformis, are strongly
      associated with immune rejection of L3 in a truncated infection model of immunity
      in sheep. Monoclonal antibody PAB-1 was used to immunopurify this antigen from T.
      colubriformis L3. The antigen is resistant to digestion with a range of proteases
      including proteinase K and does not stain on gels or blots treated with protein
      detecting reagents but does stain with carbohydrate-detecting reagents. The
      antigen is also resistant to degradation by the action of lipases and is not
      soluble in organic solvents, suggesting that lipid components are not present or
      not accessible. Treatment with glycosidases does not affect the antigen,
      indicating either that sialic acid and N-linked or O-linked sugars are not
      present or that they are not accessible to enzyme attack. The antigen is not
      destroyed by harsh alkaline degradation with up to 8 m NaOH with or without
      borohydride reducing agent, or by extensive hydrazinolysis. Strong acid
      hydrolysis with trifluoroacetic acid or boiling in hydrochloric acid for 20 min
      does destroy the antigen. The antigen migrates as a poorly defined high molecular
      weight complex on native electrophoresis gels, but is detected as a major band at
      35 kDa on SDS PAGE either by carbohydrate staining or by immunoblotting with
      antibody from immune sheep intestinal mucus and with mAb PAB-1. Proteinase K
      digestion and alkaline degradation of extracts from L3 of 10 other parasitic
      nematode species revealed that L3 of each species contained a carbohydrate
      staining molecule which can be detected by mAb PAB-1 and by mucus antibody from
      immune sheep. Because antibodies in intestinal mucus are directed against these
      antigens and may be responsible for protective immunity, carbohydrate larval
      antigens (CarLA) could represent a new family of molecules with potential as
      targets for stimulating host immunity.

PMID- 12791105
TI  - Entamoeba dispar does not produce the monocyte locomotion inhibitory factor
      (MLIF) produced by Entamoeba histolytica.

PMID- 12791104
TI  - Chemotherapy-induced, age-related changes in antischistosome antibody responses.
AB  - Humoral responses directed against Schistosoma mansoni soluble egg antigen were
      studied in Zimbabwean children before and after treatment with either
      praziquantel (PZQ) or oxamniquine (OXAM). Treated children showed a significant
      increase in the proportion producing IgE and IgG3 and in mean levels of IgE, IgM,
      IgG3 six weeks post-treatment. At 18 weeks post-treatment, the proportion of
      treated children producing IgA, IgE, and IgG3 increased while the proportion
      producing IgG1 and IgG4 decreased. Mean levels of IgA, IgE, and IgG3 were higher
      than pre-treatment levels while levels of IgG1, IgG4 and IgM were lower.
      Statistical analyses showed that the magnitude of change in levels of IgE, IgM
      and IgG3 at 6 weeks post-treatment and of IgE, IgG3 and IgG4 at 18 weeks post
      treatment was significantly greater in treated compared to untreated children,
      and there were no significant differences in immune responses between children
      treated with praziquantel and those treated with oxamniquine. The magnitude of
      change in IgE at 6 and 18 weeks, IgM at 6 weeks and IgG3 at 18 weeks post
      treatment were significantly associated with age in treated but not in untreated
      children, with the change being greater in younger children. This suggests that
      treatment induced a change in the age-antibody relationship for these isotypes,
      and that the age-antibody relationship is not robust to chemotherapy. Pre
      treatment infection levels were significantly associated (positive correlation)
      with the magnitude of change for IgE and IgG3 at 18 weeks post-treatment. Taken
      together, these results indicate that the age-antibody relationship observed in
      these children is due, at least in part, to cumulative host experience of
      parasite antigens and not host age alone.

PMID- 12791106
TI  - Pro-inflammatory (IL-1beta, IL-18) cytokines and IL-8 chemokine release by PBMC
      in response to Echinococcus multilocularis metacestode vesicles.
AB  - In humans infected with Echinococcus multilocularis, larval metacestodes will
      develop, proliferate and progressively infiltrate the surrounding host tissues by
      exogenous budding of parasitic microvesicles or cell lines which detach from the
      original tumour and thus become transported through blood or lymph vessels into
      other organs. Cellular effector mechanisms constitute the most effective means to
      restrict parasite persistence and proliferation, and here we demonstrate that E.
      multilocularis vesicle antigens will induce pro-inflammatory, regulatory and
      chemokine release by PBMC from patients. The pro-inflammatory cytokines IL-1beta
      and IL-18 were reduced in echinococcosis patients, regulatory IL-10 was similar,
      but parasite vesicle-induced IL-8 was dominant and clearly elevated in patients.
      Such selective and opposite dynamics of inflammatory cytokines and chemokine
      release may prevent overwhelming and pathogenic inflammation, and constitute an
      appropriate response for attraction of effector cells into the periparasitic
      tissues with the capacity to limit E. multilocularis metacestode proliferation
      and dissemination.

PMID- 12791107
TI  - Antigenemia is associated with low antibody response to carbohydrate determinants
      of a filarial surface antigen.
AB  - The IgG response to a filarial surface antigen (DssdI) was evaluated in
      circulating antigen (Og4C3 test) positive and negative individuals from the
      Wuchereria bancrofti endemic region of Orissa, India. Circulating filarial
      antigen (CFA) positive individuals exhibited depressed antibody levels to DssdI
      and individuals with high antibody levels were invariably CFA negative. Low IgG
      levels to DssdI are associated with CFA positivity irrespective of
      microfilaraemia and clinical status. Thus asymptomatic microfilaraemic
      individuals with antigen positivity exhibited low IgG levels similar to
      symptomatic (chronic filariasis with elephantiasis, hydrocele) or asymptomatic
      amicrofilaraemic individuals with antigenemia. Western blot analysis revealed a
      band of approximately 210 kDa reactive with CFA-negative, but not with CFA
      positive sera. DssdI was subjected to mild periodate oxidation to investigate the
      role of carbohydrate epitopes. The treatment considerably reduced the antigenic
      recognition of DssdI, stressing the immunodominance of carbohydrate residues of
      DssdI in infection-free individuals. In contrast, individuals with active
      infection failed to produce such antibodies to filarial surface carbohydrates.

PMID- 12791108
TI  - Differential lung ventilation in infants and children with pulmonary
      hyperinflation.

PMID- 12791109
TI  - Considerations for anaesthesia in children with haematological malignancy
      undergoing short procedures.
AB  - As a result of increased use of risk-directed treatment regimes, there is a
      regular requirement for short-lasting but painful procedures to be performed on
      children to aid in diagnosis or treatment. The aim of any anaesthetic technique
      is to provide analgesia and amnesia with minimal side-effects and early return to
      former activity levels. We review the implications of haematological malignancy
      in children with regard to anaesthesia and the consequences arising from both the
      disease and ensuing treatment. We outline some of the current anaesthetic
      techniques in use and review the advantages and disadvantages of each.

PMID- 12791110
TI  - Measurement of cerebral oxygenation state in anaesthetized children using the
      INVOS 5100 cerebral oximeter.
AB  - BACKGROUND: Near-infrared spectroscopy is a developing technique for monitoring
      cerebral oxygenation during anaesthesia. The aim of this study was to evaluate
      absolute values of cerebral oxygenation during stable anaesthesia conditions in
      otherwise healthy children using the recently introduced INVOS 5100 cerebral
      oximeter with a paediatric and adult sensor and to compare them with values
      obtained from the NIRO 300 oximeter. METHODS: Thirty paediatric surgical patients
      (aged 0.23-15.97 years) were studied during general anaesthesia with tracheal
      intubation and controlled ventilation. Comparative measurements of cerebral
      oxygenation were performed on the forehead with two probes within 10 min under
      stable cardiorespiratory and anaesthesia conditions. Cerebral oxygenation values
      (rSO2) obtained from the paediatric and adult INVOS 5100 sensors were compared
      with the tissue oxygenation index (TOI) obtained from the NIRO 300 cerebral
      oximeter using 4- and 5-cm emitter-detector separation. RESULTS: Cerebral rSO2
      values and the TOI values both showed a large range of cerebral oxygenation in
      the children studied (rSO2: 59-95%, TOI: 48-85%). Cerebral rSO2 values measured
      by the INVOS 5100, particularly with the paediatric sensor, were significantly
      higher than the TOI values obtained from the NIRO 300 (P < 0.0001). Agreement
      between the INVOS and NIRO oximeter was poor. CONCLUSION: The large range and the
      poor agreement of cerebral oxygenation values between the two oximeters makes it
      difficult to define a normal value. Cerebral oxygenation readings by these
      monitors, based on one single point measurement during anaesthesia, should be
      viewed with caution. Actually, there may be little indication for routine use of
      such monitoring during general anaesthesia.

PMID- 12791111
TI  - Erythropoietin therapy and acute preoperative normovolaemic haemodilution in
      infants undergoing craniosynostosis surgery.
AB  - BACKGROUND: A retrospective study was performed to evaluate whether pretreatment
      with erythropoietin and iron combined with acute preoperative normovolaemic
      haemodilution (APNH) could decrease homologous blood transfusion in
      craniosynostosis (CS) surgery. A treated group was compared with a historical
      group of infants who underwent surgery with no pretreatment. METHODS: The charts
      of 25 healthy infants who underwent CS surgery were reviewed. Nine of them
      underwent surgery with no treatment beforehand. Sixteen infants were given
      erythropoietin at a dosage of 300 U.kg -1 two times per week and iron (elemental
      iron 10 mg.kg-1.day-1) for 3 weeks before surgery. On the day of surgery APNH was
      performed after induction of general anaesthesia; a precalculated amount of
      autologous blood was withdrawn and replaced by hydroxyethyl starch 6%. RESULTS:
      Eleven of the 16 infants of the study group received only autologous blood. Five
      of 16 received homologous blood transfusion vs seven of nine infants in the
      control group. CONCLUSIONS: APNH combined with erythropoietin was effective in
      reducing homologous blood requirements during CS surgery. Further studies are
      necessary on a larger scale to assess the role of this technique in avoiding
      homologous blood transfusion and to evaluate how infants can benefit from this
      combined approach.

PMID- 12791112
TI  - Comparison between instillation of bupivacaine versus caudal analgesia for
      postoperative analgesia following inguinal herniotomy in children.
AB  - BACKGROUND: In this study we compare the postoperative pain relief for inguinal
      herniotomy in children provided by instillation of bupivacaine into the wound
      with that provided by a caudal block. METHODS: Fifty-eight children aged 0-5
      years having elective unilateral hernia repair were studied in this prospective,
      randomized, single-blind study. Anaesthesia was induced and maintained with
      oxygen, nitrous oxide, sevoflurane and propofol. Patients were randomly assigned
      to receive caudal analgesia with 1.0 ml.kg-1 body weight (BW) bupivacaine 0.25%
      or wound instillation with 0.2 ml.kg-1 BW bupivacaine 0.5% at the end of surgery.
      Pain was assessed over 24 h using a modified 10-point objective pain scale.
      During the first postoperative hour in the postanaesthesia care unit (PACU),
      intravenous (i.v.) piritramide (0.05 mg.kg-1) was administered to any child
      scoring 5 or more points on the pain scale. On the ward, rectal acetaminophen was
      administered by a staff nurse when considered necessary. RESULTS: Thirty children
      in the caudal group and 28 children in the wound instillation group were studied.
      There were no statistically significant differences between the groups regarding
      need for i.v. opioids, discharge time from the PACU and administration of
      acetaminophen. No statistically significant differences in postoperative pain
      score were observed in 16 of a total of 17 postoperative observations. No
      complications and no adverse effects were observed. CONCLUSION: Instillation of
      bupivacaine into a wound provides postoperative pain relief following hernia
      repair, which is as effective as that provided by a postoperative caudal block.

PMID- 12791113
TI  - The dose of caudal epidural analgesia and duration of postoperative analgesia.
AB  - BACKGROUND: Single dose caudal epidural is commonly utilized for postoperative
      analgesia in children. Previous studies have determined the optimal concentration
      of local anaesthetic, and the minimal volume to produce a desired dermatomal
      distribution. However, none has sought the optimal volume to administer. The
      specific aim of this study was to determine whether the volume of caudal epidural
      local anaesthetic influenced the duration of postoperative analgesia. METHODS:
      Fifty-four children aged 1-6 years and ASAPS I-II scheduled for elective inguinal
      herniorraphy were enrolled in this randomized and blinded clinical trial. They
      received a standardized general anaesthetic with one of three possible doses of
      caudal epidural analgesic: 0.7, 1.0, or 1.3 ml.kg-1 of 0.175% bupivacaine with 1
      : 200 000 epinephrine. The patients were assessed by blinded observers during in
      hospital recovery and by parents at home. RESULTS: The principal outcome measure
      of time until first postoperative analgesic requirement was similar between the
      groups (4.2, 3.6, and 4.8 h respectively). Other effects which might be altered
      by epidural analgesia, including time until first void, ambulation, and discharge
      readiness did not differ between groups. CONCLUSIONS: Increasing local
      anaesthetic dose and volume do not increase the duration of postoperative
      analgesia of caudal epidural in children undergoing inguinal herniorraphy.

PMID- 12791114
TI  - Comparison of 0.2% ropivacaine and 0.25% bupivacaine for axillary brachial plexus
      blocks in paediatric hand surgery.
AB  - BACKGROUND: The purpose of this study was to compare the use of ropivacaine 0.2%
      with bupivacaine 0.25% for axillary brachial plexus block in children undergoing
      hand surgery. METHODS: In a double-blind, randomized study, 35 children
      undergoing hand surgery received axillary brachial plexus blocks with 0.5 ml.kg-1
      of either 0.2% ropivacaine or 0.25% bupivacaine. Pain scores were noted at 0, 3,
      6, 12 and 24 h after surgery. The time to first dose of codeine phosphate and the
      total doses of all analgesics given were recorded. RESULTS: There was no
      significant difference between the two groups in pain scores, the time to first
      dose of codeine phosphate or in analgesic requirements in the first 24 h.
      CONCLUSIONS: Ropivacaine 0.2% is as effective as bupivacaine 0.25% for axillary
      brachial plexus blocks in children undergoing hand surgery.

PMID- 12791115
TI  - Does ketamine or magnesium affect posttonsillectomy pain in children?
AB  - BACKGROUND: Many previous studies have suggested a role for the N-methyl-D
      aspartate (NMDA) receptor antagonists ketamine and magnesium in decreasing
      postoperative pain and analgesic requirements in adults, but none has
      investigated these medications in children. METHODS: This randomized, double
      blind, placebo-controlled study evaluated the effects of ketamine and magnesium
      in children undergoing tonsillectomy. Eighty patients, aged 3-12 years, were
      randomly assigned to four groups. Patients received either ketamine 0.15 mg.kg-1,
      magnesium sulphate 30 mg.kg-1, ketamine 0.15 mg.kg-1 plus magnesium sulphate 30
      mg.kg-1, or placebo intravenously 5 min prior to the start of surgery.
      Intraoperative analgesia was standardized, and included fentanyl and
      dexamethasone. RESULTS: There were no differences among the groups with respect
      to pain assessment postoperatively. Compared with placebo, the treatment groups
      did not require less fentanyl in the postanaesthesia recovery room or consume
      less codeine in the first 24-h postoperatively. There was no evidence of
      synergism between ketamine and magnesium. There were no differences among the
      groups in the incidence of nausea, vomiting, sedation, bleeding, or dreaming
      postoperatively. CONCLUSION: This study did not demonstrate a decrease in pain or
      analgesic consumption in children undergoing tonsillectomy when pretreated with a
      small dose of ketamine and/or magnesium.

PMID- 12791116
TI  - Double-blind randomized placebo-controlled trial of the effect of ketamine on
      postoperative morphine consumption in children following appendicectomy.
AB  - BACKGROUND: Ketamine has an opioid sparing effect following surgery in adults.
      This study investigated whether a similar effect is seen following appendicectomy
      in paediatric patients. METHODS: Seventy-five ASA 1 or 2 children aged 7-16 years
      were recruited, and randomly allocated to one of three groups. Following a
      standard anaesthetic for appendicectomy, all were prescribed patient controlled
      analgesia (PCA) morphine with paracetamol and nonsteroidal anti-inflammatory
      drugs (NSAIDS) as required for postoperative analgesia. In addition the control
      group received a saline infusion postoperatively, the ketamine bolus group
      received 500 micro g.kg-1 intravenous (i.v.) ketamine preincision and a saline
      infusion postoperatively, and the ketamine infusion group received 500 micro g.kg
      1 i.v. ketamine preincision and a ketamine infusion at 4 micro g.kg-1 min-1
      postoperatively. Morphine consumption, rescue analgesia requirement and side
      effects were recorded postoperatively. RESULTS: There was no difference in
      morphine consumption between the groups. The ketamine infusion group required
      more doses of rescue analgesia and reported more side-effects than the control
      group. Five patients, all in the ketamine infusion group, reported
      hallucinations. CONCLUSIONS: In this paediatric population intravenous ketamine
      did not have a morphine sparing effect. The increased incidence of side-effects,
      especially hallucinations, reported by patients given a ketamine infusion may
      limit the further use of postoperative ketamine in children.

PMID- 12791117
TI  - Comparison of patient-controlled analgesia with and without a background infusion
      after appendicectomy in children.
AB  - BACKGROUND: There have been many studies using patient-controlled analgesia (PCA)
      and opioids for postoperative analgesia in children. In this study, we
      investigated the efficacy, usefulness and analgesic consumption of two different
      PCA programmes [bolus dose alone (BD) or bolus dose with background infusion (BD
      + BI)] to evaluate postoperative analgesia for children after emergency
      appendicectomy. METHODS: Forty children, aged between 6 and 15 years and ASA
      class I or II, undergoing emergency appendicectomy were randomly allocated into
      two groups. The children were given a loading dose of pethidine 0.3 mg.kg-1 and
      150 micro g.kg-1 bolus intravenously in group BD (n = 20) and pethidine 0.3 mg.kg
      1 loading dose, 75 micro g.kg-1 bolus and 15 micro g.kg-1.h-1 background infusion
      in group BD + BI (n = 20). The lockout interval was 20 min in both groups.
      RESULTS: There were no significant differences in pain, sedation and nausea
      scores during the 24-h postoperative period between the groups (P > 0.05).
      Pethidine consumption was significantly lower in group BD + BI than that in group
      BD for the first 24-h period (P < 0.05). CONCLUSIONS: We demonstrated that both
      these PCA programmes were effective and reliable for postoperative pain relief in
      children. We believe that giving information about PCA to the children and their
      parents is useful during the preoperative period. However, the background
      infusion with lower bolus dose in PCA did not increase pethidine consumption.

PMID- 12791118
TI  - Life threatening unilateral pulmonary overinflation might be more successfully
      treated by contralateral selective intubation than by emergency pneumonectomy.
AB  - During a period of 3 years, three infants were admitted to our hospital for
      unilateral emergency pneumonectomy due to life threatening overinflation of one
      lung, preventing adequate ventilation of the unaffected contralateral side. All
      three patients were able to be stabilized by unilateral selective bronchial
      intubation of the unaffected lung after bronchoscopy, ruling out a flap valve
      mechanism. No emergency pneumonectomies were required. In one patient, lung
      function of the overinflated side (three lobes) recovered fully and, in the two
      remaining patients, one lobe of the overinflated side recovered. The overinflated
      lobes were removed later by elective surgery, thus not exposing the children to a
      potentially dangerous emergency operation. These results are in contrast with
      reports in the literature. Emergency pneumonectomy in neonates and infants due to
      overinflation of one lung may be avoided by selective unilateral intubation of
      the main stem bronchus of the compressed lung.

PMID- 12791119
TI  - Differential lung ventilation in an infant using LMA and a long tracheal tube.
AB  - This is a case report of differential lung ventilation in an infant using a
      conventional laryngeal mask airway (LMATM) and a commercially available longer
      paediatric tracheal tube. This 2-month-old infant had her left-sided congenital
      diaphragmatic hernia repaired on the sixth day of her life, and had been
      mechanically ventilated. The right middle lobe became grossly emphysematous and
      herniated into the left side of the chest, and the right lower lobe became
      totally atelectatic. A right middle lobe lobectomy was planned. To avoid
      hyperinflating the right middle lobe, and to expand the right lower lobe without
      providing a high airway pressure on the left lung, the dependent lung (i.e. left
      lung) was ventilated with an LMA, and the right lower lobe was expanded with a
      long tracheal tube inserted through the LMA via the swivel connector. This
      combination of a conventional LMA and a commercially available longer paediatric
      tracheal tube could be another way of providing differential ventilation in
      infants.

PMID- 12791120
TI  - Postobstructive pulmonary oedema during anaesthesia in children with
      mucopolysaccharidoses.
AB  - We present case reports of five patients with severe forms of
      mucopolysaccharidoses who developed postobstructive pulmonary oedema during
      anaesthesia. The difficulties of anaesthesia in these patients and the particular
      predisposition that these patients exhibit for the development of postobstructive
      pulmonary oedema is discussed.

PMID- 12791122
TI  - Anaesthesia for an adolescent with mitochondrial encephalomyopathy-lactic
      acidosis-stroke-like episodes syndrome.
AB  - Anaesthesia for patients with mitochondrial disorders occurs with regularity,
      either for a diagnostic or therapeutic procedure associated with the syndrome or
      for unassociated surgery. We report the case of a 17-year-old boy with
      mitochondrial encephalomyopathy-lactic acidosis-stroke-like episodes (MELAS)
      syndrome who underwent a laparotomy for fundoplication. The potential hazards of
      anaesthesia for this patient, and the steps taken to avoid them, are discussed.

PMID- 12791121
TI  - Double trouble: prolapsing epiglottis and unexpected dual pathology in an infant.
AB  - A 3-week-old full-term female neonate was admitted with a 4-day history of
      episodic stridor, desaturations and difficult feeding. Initial assessment using
      fluoroscopy suggested distal tracheomalacia. Inhalational induction for
      examination under anaesthesia of the upper airway at 4 weeks of age caused almost
      complete airway obstruction due to severe anterior, or epiglottic,
      laryngomalacia. This airway obstruction was unresponsive to continuous positive
      airway pressure, the use of an oropharyngeal airway and hand ventilation and
      required urgent tracheal intubation using suxamethonium. Epiglottopexy, a
      relatively unknown procedure, was performed uneventfully 2 days later, with
      complete relief of the respiratory compromise. However, the infant remained
      desaturated postoperatively. A ventilation perfusion scan subsequently revealed
      multiple pulmonary arteriovenous malformations, unsuitable for embolization and
      requiring nocturnal home oxygen therapy. Review at 3 months of age found a
      thriving infant with no airway obstruction and good epiglottic positioning on
      examination under anaesthesia. Although the patient's oxygen requirements had
      diminished, the long-term outcome remains uncertain.

PMID- 12791123
TI  - Anaesthetic management of a child with Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome is characterized by tetrasomy of the short arm of
      chromosome 12p, which produces mental retardation of varying degrees and
      dysmorphic characteristics. We describe anaesthesia in a 2-year-old child
      affected by this syndrome who underwent surgery for orchidopexy. Anaesthetic
      consisted of an inhalation mixture of O2, N2O and sevoflurane, together with an
      inguinal block with ropivacaine and administration of alfentanil plus ketorolac.
      Tracheal intubation was uneventful. No complications of any type were observed.

PMID- 12791124
TI  - Response to editorial by G. Chalkiadis.

PMID- 12791125
TI  - Infection-induced pulmonary hypertension crisis after Rastelli procedure.

PMID- 12791126
TI  - Reliability of emergency drugs.

PMID- 12791128
TI  - Congress report. The Asian Society of Paediatric Anaesthesiologists participation
      at the 50th National Conference of Indian Society of anaesthesiologists 2002 in
      Coimbatore, India.

PMID- 12791129
TI  - Autoinduction and signal transduction in the regulation of staphylococcal
      virulence.
AB  - The accessory genes of Staphylococcus aureus, including those involved in
      pathogenesis, are controlled by a complex regulatory network that includes at
      least four two-component systems, one of which, agr, is a quorum sensor, an
      alternative sigma factor and a large set of transcription factors, including at
      least two of the superantigen genes, tst and seb. These regulatory genes are
      hypothesized to act in a time- and population density-dependent manner to
      integrate signals received from the external environment with the internal
      metabolic machinery of the cell, in order to achieve the production of particular
      subsets of accessory/virulence factors at the time and in quantities that are
      appropriate to the needs of the organism at any given location. From the
      standpoint of pathogenesis, the regulatory agenda is presumably tuned to
      particular sites in the host organism. To address this hypothesis, it will be
      necessary to understand in considerable detail the regulatory interactions among
      the organism's numerous controlling systems. This review is an attempt to
      integrate a large body of data into the beginnings of a model that will hopefully
      help to guide research towards a full-scale test.

PMID- 12791130
TI  - Characterization of RAT, an autolysis regulator in Staphylococcus aureus.
AB  - In trying to identify genetic loci involved in the regulation of cap5 genes in
      Staphylococcus aureus, we isolated a transposon mutant that exhibited a growth
      defect, enhanced autolysis and increased sensitivity to Triton X-100 and
      penicillin, attributable in part to increased murein hydrolase activity. Analysis
      of the chromosomal sequence flanking the transposon insertion site revealed that
      the gene disrupted in the mutant encodes an open reading frame of 147 amino
      acids. We named this gene rat, which stands for regulator of autolytic activity.
      Sequence analysis indicated that Rat is homologous to the MarR and, to a lesser
      extent, the SarA protein families. Mutations in rat resulted in decreased
      expression of known autolytic regulators lytSR, lrgAB and arlRS. Gel shift
      studies indicated that Rat binds to the lytRS and arlRS promoters, thus
      confirming Rat as a DNA-binding protein to these known repressors of autolytic
      activity. As anticipated, rat appears to be a negative regulator of autolysin
      genes including lytM and lytN. These data suggest that the rat gene product is an
      important regulator of autolytic activity in S. aureus.

PMID- 12791131
TI  - Haemophore-mediated signal transduction across the bacterial cell envelope in
      Serratia marcescens: the inducer and the transported substrate are different
      molecules.
AB  - Numerous bacteria are able to use free and haemoprotein-bound haem as iron
      sources because of the action of small secreted proteins called haemophores.
      Haemophores have very high affinity for haem, and can therefore extract haem from
      the haem-carrier proteins and deliver it to the cells by means of specific cell
      surface receptors. Haem is then taken up and the empty haemophores are recycled.
      Here, we report a study of the regulation of the Serratia marcescens has operon
      which is involved in haemophore-dependent haem acquisition. We characterized two
      genes encoding proteins homologous to specific ECF sigma and antisigma factors.
      We showed that they regulate the synthesis of the haemophore-specific outer
      membrane receptor, HasR, by a signal transduction mechanism similar to the
      siderophore surface-signalling systems. We also showed the essential role of HasR
      itself in this process. Using haem-loaded and haem-free haemophore, we identified
      the stimulus for the HasR-mediated signal transduction as being the binding of
      the haem-loaded haemophore to HasR. Thus, unlike siderophore-uptake systems, in
      which the signalling molecule is the transported substrate itself, in the
      haemophore-dependent haem uptake system the inducer and the transported substrate
      are different compounds.

PMID- 12791132
TI  - Membrane-specific targeting of green fluorescent protein by the Tat pathway in
      the cyanobacterium Synechocystis PCC6803.
AB  - The transport and sorting of extracytoplasmic proteins in cyanobacteria is made
      complex by the presence of a highly differentiated membrane system. Proteins
      destined for the periplasm and thylakoid lumen are initially transported by Sec-
      and Tat-type pathways but little is known of the mechanisms that ultimately
      direct them to the correct destinations. We have generated a Synechocystis
      PCC6803 transformant that expresses a fusion protein comprising the Tat-specific
      targeting signal of Escherichia coli TorA linked to green fluorescent protein
      (GFP). Immunoblotting indicates the presence of mature-size GFP but no precursor
      form, demonstrating that efficient translocation has taken place. Confocal
      microscopy and immunogold electron microscopy reveal GFP to be almost exclusively
      located in the periplasm, with almost no protein evident in the thylakoid
      network. These data point to the operation of highly effective sorting pathways
      for soluble proteins in this cyanobacterium. The observed sorting of the GFP
      suggests that either (a) the Tat apparatus is located only in the plasma membrane
      or (b) the TorA-GFP is targeted across either membrane but the GFP is
      subsequently directed to the periplasm, perhaps by a default sorting pathway to
      this compartment.

PMID- 12791133
TI  - Consequences of reductive evolution for gene expression in an obligate
      endosymbiont.
AB  - The smallest cellular genomes are found in obligate symbiotic and pathogenic
      bacteria living within eukaryotic hosts. In comparison with large genomes of free
      living relatives, these reduced genomes are rearranged and have lost most
      regulatory elements. To test whether reduced bacterial genomes incur reduced
      regulatory capacities, we used full-genome microarrays to evaluate
      transcriptional response to environmental stress in Buchnera aphidicola, the
      obligate endosymbiont of aphids. The 580 genes of the B. aphidicola genome
      represent a subset of the 4500 genes known from the related organism, Escherichia
      coli. Although over 20 orthologues of E. coli heat stress (HS) genes are retained
      by B. aphidicola, only five were differentially expressed after near-lethal heat
      stress treatments, and only modest shifts were observed. Analyses of upstream
      regulatory regions revealed loss or degradation of most HS (sigma32) promoters.
      Genomic rearrangements downstream of an intact HS promoter yielded upregulation
      of a functionally unrelated and an inactivated gene. Reanalyses of comparable
      experimental array data for E. coli and Bacillus subtilis revealed that genome
      wide differential expression was significantly lower in B. aphidicola. Our
      demonstration of a diminished stress response validates reports of temperature
      sensitivity in B. aphidicola and suggests that this reduced bacterial genome
      exhibits transcriptional inflexibility.

PMID- 12791134
TI  - The large linear plasmid pSLA2-L of Streptomyces rochei has an unusually
      condensed gene organization for secondary metabolism.
AB  - The complete nucleotide sequence of the large linear plasmid pSLA2-L in
      Streptomyces rochei strain 7434AN4 has been determined. pSLA2-L was found to be
      210 614 bp long with a GC content of 72.8% and carries 143 open reading frames.
      It is especially noteworthy that three-quarters of the pSLA2-L DNA is occupied by
      secondary metabolism-related genes, namely two type I polyketide synthase (PKS)
      gene clusters for lankacidin and lankamycin, a mithramycin synthase-like type II
      PKS gene cluster, a carotenoid biosynthetic gene cluster and many regulatory
      genes. In particular, the lankacidin PKS is unique, because it may be a mixture
      of modular- and iterative-type PKSs and carries a fusion protein of non-ribosomal
      peptide synthetase and PKS. It is also interesting that all the homologues of the
      afsA, arpA, adpA and strR genes in the A-factor regulatory cascade in
      Streptomyces griseus were found on pSLA2-L, and disruption of the afsA homologue
      caused non-production of both lankacidin and lankamycin. These results, together
      with the finding of three possible replication origins at 50-63 kb from the right
      end, suggest that the present form of pSLA2-L might have been generated by a
      series of insertions of the biosynthetic gene clusters into the left side of the
      original plasmid.

PMID- 12791135
TI  - Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili
      mutants.
AB  - Biofilm formation by Gfp-tagged Pseudomonas aeruginosa PAO1 wild type, flagella
      and type IV pili mutants in flow chambers irrigated with citrate minimal medium
      was characterized by the use of confocal laser scanning microscopy and comstat
      image analysis. Flagella and type IV pili were not necessary for P. aeruginosa
      initial attachment or biofilm formation, but the cell appendages had roles in
      biofilm development, as wild type, flagella and type IV pili mutants formed
      biofilms with different structures. Dynamics and selection during biofilm
      formation were investigated by tagging the wild type and flagella/type IV mutants
      with Yfp and Cfp and performing time-lapse confocal laser scanning microscopy in
      mixed colour biofilms. The initial microcolony formation occurred by clonal
      growth, after which wild-type P. aeruginosa bacteria spread over the substratum
      by means of twitching motility. The wild-type biofilms were dynamic compositions
      with extensive motility, competition and selection occurring during development.
      Bacterial migration prevented the formation of larger microcolonial structures in
      the wild-type biofilms. The results are discussed in relation to the current
      model for P. aeruginosa biofilm development.

PMID- 12791136
TI  - Aromatic amino acids at the surface of InlB are essential for host cell invasion
      by Listeria monocytogenes.
AB  - The surface protein InlB of the pathogen Listeria monocytogenes promotes invasion
      of this bacterium into host cells by binding to and activating the receptor
      tyrosine kinase Met. The curved leucine-rich repeat (LRR) domain of InlB, which
      is essential for this process, contains a string of five surface-exposed aromatic
      amino acid residues positioned along its concave face. Here, we show that the
      replacement of four of these residues (F104, W124, Y170 or Y214) by serine leads
      to a complete loss of uptake of latex beads coated with InlB', a truncated
      functional variant of InlB. The mutants correspondingly display severely reduced
      binding to Met. To abrogate fully invasion of bacteria expressing full-length
      InlB, exchange of at least four aromatic amino acids is required. We conclude
      that InlB binds to Met through its concave surface of the LRR domain, and that
      aromatic amino acids are critical for binding and signalling before invasion.

PMID- 12791137
TI  - Isolation of Listeria monocytogenes mutants with high-level in vitro expression
      of host cytosol-induced gene products.
AB  - The facultative intracellular bacterial pathogen Listeria monocytogenes
      dramatically increases the expression of several key virulence factors upon entry
      into the host cell cytosol. actA, the protein product of which is required for
      cell-to-cell spread of the bacterium, is expressed at low to undetectable levels
      in vitro and increases in expression more than 200-fold after L. monocytogenes
      escape from the phagosome. To identify bacterial factors that participate in the
      intracellular induction of actA expression, L. monocytogenes mutants expressing
      high levels of actA during in vitro growth were selected after chemical
      mutagenesis. The resulting mutant isolates displayed a wide range of actA
      expression levels, and many were less sensitive to environmental signals that
      normally mediate repression of virulence gene expression. Several isolates
      contained mutations affecting actA gene expression that mapped at least 40 kb
      outside the PrfA regulon, supporting the existence of additional regulatory
      factors that contribute to virulence gene expression. Two actA in vitro
      expression mutants contained novel mutations within PrfA, a key regulator of L.
      monocytogenes virulence gene expression. PrfA E77K and PrfA G155S mutations
      resulted in high-level expression of PrfA-dependent genes, increased bacterial
      invasion of epithelial cells and increased virulence in mice. Both prfA mutant
      strains were significantly less motile than wild-type L. monocytogenes. These
      results suggest that, although constitutive activation of PrfA and PrfA-dependent
      gene expression may enhance L. monocytogenes virulence, it may conversely hamper
      the bacterium's ability to compete in environments outside host cells.

PMID- 12791138
TI  - The kinetic properties of the carboxy terminal domain of the Bacillus
      licheniformis 749/I BlaR penicillin-receptor shed a new light on the derepression
      of beta-lactamase synthesis.
AB  - To study the properties of the BlaR penicillin-receptor involved in the induction
      of the Bacillus licheniformisbeta-lactamase, the water-soluble carboxy terminal
      domain of the protein (BlaR-CTD) was overproduced in the periplasm of Escherichia
      coli JM105 and purified to protein homogeneity. Its interactions with various
      beta-lactam antibiotics were studied. The second-order acylation rate constants
      k2/K' ranged from 0.0017 to more than 1 micro M-1s-1 and the deacylation rate
      constants were lower than 4 x 10-5 s-1. These values imply a rapid to very rapid
      formation of a stable acylated adduct. BlaR-CTD is thus one of the most sensitive
      penicillin-binding proteins presently described. In the light of these results,
      the kinetics of beta-lactamase induction in Bacillus licheniformis were re
      examined. When starting with a rather high cell density, a good beta-lactamase
      substrate such as benzylpenicillin is too sensitive to beta-lactamase-mediated
      hydrolysis to allow full induction. By contrast, a poor beta-lactamase substrate
      (7-aminocephalosporanic acid) can fully derepress beta-lactamase expression under
      conditions where interference of the antibiotic with cell growth is observed.
      These results suggest that acylation of the penicillin receptor is a necessary,
      but not sufficient, condition for full induction.

PMID- 12791139
TI  - Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and
      virulence.
AB  - Clp proteolytic complexes are essential for virulence and for survival under
      stress conditions in several pathogenic bacteria. Recently, a study using
      signature-tagged mutagenesis identified the ClpX ATPase as also being required
      for virulence in Staphylococcus aureus. Presently, we have constructed deletion
      mutants removing either ClpX or the proteolytic subunit, ClpP, in S. aureus 8325
      4 in order to examine a putative link between stress tolerance and virulence.
      When exposed to stress, we found that, although clpP mutant cells were sensitive
      to conditions generating misfolded proteins, the absence of ClpX improved
      survival. In the presence of oxidative stress or at low temperature, both ClpP
      and ClpX were important for growth. Virulence was examined in a murine skin
      abscess model and was found to be severely attenuated for both mutants. S. aureus
      pathogenicity is largely dependent on a set of extracellular and cell wall
      associated proteins. In the mutant cells, the amount of alpha-haemolysin (hla)
      and several other extracellular proteins was greatly decreased, and analysis of
      hla expression revealed that the reduction occurred at the transcriptional level.
      Essential for transcriptional regulation of hla is the quorum-sensing agr locus.
      Interestingly, the absence of ClpX or ClpP reduced both transcription of the agr
      effector molecule, RNA III, and the activity of the autoinducing peptide (AIP).
      In addition, ClpX was required independently of ClpP for transcription of spa
      encoding Protein A. Thus, our results indicate that ClpX and ClpP contribute to
      virulence by controlling the activity of major virulence factors rather than by
      promoting stress tolerance.

PMID- 12791140
TI  - Structural, genetic and functional characterization of the flagellin
      glycosylation process in Helicobacter pylori.
AB  - Mass spectrometry analyses of the complex polar flagella from Helicobacter pylori
      demonstrated that both FlaA and FlaB proteins are post-translationally modified
      with pseudaminic acid (Pse5Ac7Ac, 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l
      manno -n o n-ulosonic acid). Unlike Campylobacter, flagellar glycosylation in
      Helicobacter displays little heterogeneity in isoform or glycoform distribution,
      although all glycosylation sites are located in the central core region of the
      protein monomer in a manner similar to that found in Campylobacter. Bioinformatic
      analysis revealed five genes (HP0840, HP0178, HP0326A, HP0326B, HP0114)
      homologous to other prokaryote genes previously reported to be involved in
      motility, flagellar glycosylation or polysaccharide biosynthesis. Insertional
      mutagenesis of four of these homologues in Helicobacter (HP0178, HP0326A,
      HP0326B, HP0114) resulted in a non-motile phenotype, no structural flagella
      filament and only minor amounts of flagellin protein detectable by Western
      immunoblot. However, mRNA levels for the flagellin structural genes remained
      unaffected by each mutation. In view of the combined bioinformatic and structural
      evidence indicating a role for these gene products in glycan biosynthesis,
      subsequent investigations focused on the functional characterization of the
      respective gene products. A novel approach was devised to identify biosynthetic
      sugar nucleotide precursors from intracellular metabolic pools of parent and
      isogenic mutants using capillary electrophoresis-electrospray mass spectrometry
      (CE-ESMS) and precursor ion scanning. HP0326A, HP0326B and the HP0178 gene
      products are directly involved in the biosynthesis of the nucleotide-activated
      form of Pse, CMP-Pse. Mass spectral analyses of the cytosolic extract from the
      HP0326A and HP0326B isogenic mutants revealed the accumulation of a mono- and a
      diacetamido trideoxyhexose UDP sugar nucleotide precursor.

PMID- 12791141
TI  - Identification of nuclear proteins that interact differentially with Plasmodium
      falciparum var gene promoters.
AB  - The Plasmodium falciparum virulence factor PfEMP1 is responsible for both
      antigenic variation and cytoadherence of infected erythrocytes in malaria.
      Approximately 50 var genes per parasite genome code for this highly polymorphic
      surface protein. We showed recently that chromosome-central and subtelomeric var
      genes are controlled by different promoters. Here, we report that transcriptional
      repression of var genes located in different chromosomal regions occurs by
      different mechanisms. Subtelomeric var gene transcription is repressed 4-8 h
      before that of chromosome-central var genes. Both repression events coincide with
      the shifted expression of two distinct nuclear proteins binding specifically to
      conserved sequence motifs, SPE1 and CPE, present in the respective promoter.
      Furthermore, a reiterated and highly conserved subtelomeric var promoter element
      (SPE2) interacts with a nuclear factor exclusively expressed during S-phase.
      Promoter analysis by transient transfection suggested direct involvement of these
      interactions in var gene repression and silencing, and identified regions
      implicated in transcriptional activation of var genes.

PMID- 12791142
TI  - Bile salts and fatty acids induce the expression of Escherichia coli AcrAB
      multidrug efflux pump through their interaction with Rob regulatory protein.
AB  - AcrAB of Escherichia coli, an archetype among bacterial multidrug efflux pumps,
      exports an extremely wide range of substrates including solvents, dyes,
      detergents and antimicrobial agents. Its expression is regulated by three
      XylS/AraC family regulators, MarA, SoxS and Rob. Although MarA and SoxS
      regulation works by the alteration of their own expression levels, it was not
      known how Rob, which is constitutively expressed, exerts its regulatory action.
      We show here that the induction of the AcrAB efflux pump by decanoate and the
      more lipophilic unconjugated bile salts is mediated by Rob, and that the low
      molecular-weight inducers specifically bind to the C-terminal, non-DNA-binding
      domain of Rob. Induction of Rob is not needed for induction of AcrAB, and we
      suggest that the inducers act by producing conformational alterations in pre
      existing Rob, as was suggested recently (Rosner, Dangi, Gronenborn and Martin, J
      Bacteriol 184: 1407-1416, 2002). Decanoate and unconjugated bile salts, which are
      present in the normal habitat of E. coli, were further shown to make the bacteria
      more resistant to lipophilic antibiotics, at least in part because of the
      induction of the AcrAB efflux pump. Thus, it is likely that E. coli is protecting
      itself by the Rob-mediated upregulation of AcrAB against the harmful effects of
      bile salts and fatty acids in the intestinal tract.

PMID- 12791143
TI  - Escherichia coli SspA is a transcription activator for bacteriophage P1 late
      genes.
AB  - The stringent starvation protein A (SspA), an Escherichia coli RNA polymerase
      (RNAP)-associated protein, has been reported to be essential for lytic growth of
      bacteriophage P1. Unlike P1 early promoters, P1 late promoters are not recognized
      by RNAP alone. A phage-encoded early protein, Lpa (late promoter activator
      protein, formerly called gp10), has been shown to be required for P1 late
      transcription in vivo. Here, we demonstrate that SspA is a transcription
      activator for P1 late genes. Our results indicated that Lpa is not limiting in an
      sspA mutant. However, the transcription of P1 late genes was deficient in an sspA
      mutant in vivo. We demonstrated that SspA/Lpa are required for transcription
      activation of the P1 late promoter Ps in vitro. In addition, SspA and Lpa were
      shown to facilitate the binding of RNAP to Ps late promoter DNA. Activation of
      late transcription by SspA/Lpa was dependent on holoenzyme containing sigma70 but
      not sigmaS, indicating that the two activators discriminate between the two forms
      of the holoenzyme. Furthermore, P1 early gene expression was downregulated in the
      wild-type background, whereas it persisted in the sspA mutant background,
      indicating that SspA/Lpa mediate the transcriptional switch from the early to the
      late genes during P1 lytic growth. Thus, this work provides the first evidence
      for a function of the E. coli RNAP-associated protein SspA.

PMID- 12791144
TI  - Global regulation by CsrA in Salmonella typhimurium.
AB  - CsrA is a regulator of invasion genes in Salmonella enterica serovar Typhimurium.
      To investigate the wider role of CsrA in gene regulation, we compared the
      expression of Salmonella genes in a csrA mutant with those in the wild type using
      a DNA microarray. As expected, we found that expression of Salmonella
      pathogenicity island 1 (SPI-1) invasion genes was greatly reduced in the csrA
      mutant, as were genes outside the island that encode proteins translocated into
      eukaryotic cells by the SPI-1 type III secretion apparatus. The flagellar
      synthesis operons, flg and fli, were also poorly expressed, and the csrA mutant
      was aflagellate and non-motile. The genes of two metabolic pathways likely to be
      used by Salmonella in the intestinal milieu also showed reduced expression: the
      pdu operon for utilization of 1,2-propanediol and the eut operon for ethanolamine
      catabolism. Reduced expression of reporter fusions in these two operons confirmed
      the microarray data. Moreover, csrA was found to regulate co-ordinately the cob
      operon for synthesis of vitamin B12, required for the metabolism of either 1,2
      propanediol or ethanolamine. Additionally, the csrA mutant poorly expressed the
      genes of the mal operon, required for transport and use of maltose and
      maltodextrins, and had reduced amounts of maltoporin, normally a dominant protein
      of the outer membrane. These results show that csrA controls a number of gene
      classes in addition to those required for invasion, some of them unique to
      Salmonella, and suggests a co-ordinated bacterial response to conditions that
      exist at the site of bacterial invasion, the intestinal tract of a host animal.

PMID- 12791145
TI  - Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system.
AB  - Vibrio vulnificus is a halophilic estuarine bacterium that causes fatal
      septicaemia and necrotizing wound infections. We tested whether V. vulnificus
      produces signalling molecules (autoinducer 1 and/or 2) stimulating Vibrio harveyi
      quorum-sensing system 1 and/or 2. Although there was no evidence for signalling
      system 1, we found that V. vulnificus produced a signalling activity in the
      culture supernatant that induced luminescence expression in V. harveyi through
      signalling system 2. Maximal autoinducer 2 (AI-2) activity was observed during
      mid-exponential to early stationary phase and disappeared in the late stationary
      phase when V. vulnificus was grown in heart infusion broth containing 2.5% NaCl.
      V. vulnificus showed increased signalling activity when it was cultured in the
      presence of glucose (0.5%) and at low pH (pH 6.0). From a cosmid library of V.
      vulnificus type strain ATCC 29307, we have identified the AI-2 synthase gene
      (luxSVv) showing 80% identity with that of V. harveyi (luxSVh) at the amino acid
      level. To investigate the pathogenic role of luxSVv, a deletion mutant of the
      clinical isolate V. vulnificus MO6-24/O was constructed. The luxSVv mutant showed
      a significant delay in protease production and an increase in haemolysin
      production. The decreased protease and increased haemolysin activities were
      restored to the isogenic wild-type level by complementation with the wild-type
      luxSVv allele. The change in phenotypes was also complemented by logarithmic
      phase spent media produced by the wild-type bacteria. Transcriptional activities
      of the haemolysin gene (vvhA) and protease gene (vvpE) were also observed in the
      mutant using chromosomal PvvhA::lacZ and PvvpE::lacZ transcriptional reporter
      constructs: transcription of vvhA was increased and of vvpE decreased by the
      mutation. The mutation resulted in an attenuation of lethality to mice.
      Intraperitoneal LD50 of the luxSVv mutant increased by 10- and 750-fold in ferric
      ammonium citrate-non-overloaded and ferric ammonium citrate-overloaded mice
      respectively. The time required for the death of mice was also significantly
      delayed in the luxSVv mutant. Cytotoxic activity of the organism against HeLa
      cells, measured by lactate dehydrogenase (LDH) release assay, was also decreased
      significantly by the mutation. Taken together, the V. vulnificus LuxS quorum
      sensing system seems to play an important role in co-ordinating the expression of
      virulence factors.

PMID- 12791146
TI  - Transcriptional regulation of the ospAB and ospC promoters from Borrelia
      burgdorferi.
AB  - OspA, OspB and OspC are the major outer surface proteins of Borrelia burgdorferi
      that are differentially synthesized in response to environmental conditions,
      including culture temperature. We found that DNA was more negatively supercoiled
      in B. burgdorferi cultures grown at 23 degrees C compared with cultures grown at
      35-37 degrees C. We examined the regulation of ospAB and ospC transcription by
      temperature and DNA supercoiling. DNA supercoiling was relaxed by adding
      coumermycin A1, an antibiotic that inhibits DNA gyrase. Syntheses of the major
      outer surface proteins, expression of the ospA and ospC genes and the activities
      of the ospAB operon and ospC gene promoters were assayed. ospA product levels
      decreased, whereas ospC product levels increased after shifting from 23 degrees C
      to 35 degrees C or after adding coumermycin A1. In addition, OspC synthesis was
      higher in a gyrB mutant than in wild-type B. burgdorferi. Promoter activity was
      quantified using cat reporter fusions. Increasing temperature or relaxing
      supercoiled DNA resulted in a decrease in ospAB promoter activity in B.
      burgdorferi, but not in Escherichia coli, as well as an increase in ospC promoter
      activity in both bacteria. ospC promoter activity was increased in an E. coli
      gyrB mutant with an attenuated DNA supercoiling phenotype. These results suggest
      that B. burgdorferi senses environmental changes in temperature by altering the
      level of DNA supercoiling, which then affects the expression of the ospAB operon
      and the ospC gene. This implies that DNA supercoiling acts as a signal transducer
      for environmental regulation of outer surface protein synthesis.

PMID- 12791147
TI  - Ribosome-DnaK interactions in relation to protein folding.
AB  - Bacterial ribosomes or their 50S subunit can refold many unfolded proteins. The
      folding activity resides in domain V of 23S RNA of the 50S subunit. Here we show
      that ribosomes can also refold a denatured chaperone, DnaK, in vitro, and the
      activity may apply in the folding of nascent DnaK polypeptides in vivo. The
      chaperone was unusual as the native protein associated with the 50S subunit
      stably with a 1:1 stoichiometry in vitro. The binding site of the native protein
      appears to be different from the domain V of 23S RNA, the region with which
      denatured proteins interact. The DnaK binding influenced the protein folding
      activity of domain V modestly. Conversely, denatured protein binding to domain V
      led to dissociation of the native chaperone from the 50S subunit. DnaK thus
      appears to depend on ribosomes for its own folding, and upon folding, can rebind
      to ribosome to modulate its general protein folding activity.

PMID- 12791148
TI  - Different roles of the Mre11 complex in the DNA damage response in Aspergillus
      nidulans.
AB  - The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the
      cellular DNA damage response. Mutations in scaANBS1, which encodes the apparent
      homologue of human Nbs1 in Aspergillus nidulans, inhibit growth in the presence
      of the anti-topoisomerase I drug camptothecin. We have used the scaANBS1 cDNA as
      a bait in a yeast two-hybrid screening and report the identification of the A.
      nidulans Mre11 homologue (mreA). The inactivated mreA strain was more sensitive
      to several DNA damaging and oxidative stress agents. Septation in A. nidulans is
      dependent not only on the uvsBATR gene, but also on the mre11 complex. scaANBS1
      and mreA genes are both involved in the DNA replication checkpoint whereas mreA
      is specifically involved in the intra-S-phase checkpoint. ScaANBS1 also
      participates in G2-M checkpoint control upon DNA damage caused by MMS. In
      addition, the scaANBS1 gene is also important for ascospore viability, whereas
      mreA is required for successful meiosis in A. nidulans. Consistent with this
      view, the Mre11 complex and the uvsCRAD51 gene are highly expressed at the mRNA
      level during the sexual development.

PMID- 12791149
TI  - RdgB acts to avoid chromosome fragmentation in Escherichia coli.
AB  - Bacterial RecA protein is required for repair of two-strand DNA lesions that
      disable whole chromosomes. recA mutants are viable, suggesting a considerable
      cellular capacity to avoid these chromosome-disabling lesions. recA-dependent
      mutants reveal chromosomal lesion avoidance pathways. Here we characterize one
      such mutant, rdgB/yggV, deficient in a putative inosine/xanthosine
      triphosphatase, conserved throughout kingdoms of life. The rdgB recA lethality is
      suppressed by inactivation of endonuclease V (gpnfi) specific for DNA
      hypoxanthines/xanthines, suggesting that RdgB either intercepts improper DNA
      precursors dITP/dXTP or works downstream of EndoV in excision repair of
      incorporated hypoxathines/xanthines. We find that DNA isolated from rdgB mutants
      contains EndoV-recognizable modifications, whereas DNA from nfi mutants does not,
      substantiating the dITP/dXTP interception by RdgB. rdgB recBC cells are inviable,
      whereas rdgB recF cells are healthy, suggesting that chromosomes in rdgB mutants
      suffer double-strand breaks. Chromosomal fragmentation is indeed observed in rdgB
      recBC mutants and is suppressed in rdgB recBC nfi mutants. Thus, one way to avoid
      chromosomal lesions is to prevent hypoxanthine/xanthine incorporation into DNA
      via interception of dITP/dXTP.

PMID- 12791150
TI  - In vitro retention force changes of prefabricated attachments for overdentures.
AB  - Changes in the retention force of six prefabricated spherical and cylindrical
      attachments were examined in vitro under continuous loading. The testing machine
      permitted insertion-separation cycles to be tested under reproducible conditions
      while a calibrated measuring device determined the insertion and retention
      forces. At the beginning, during the so-called run-in period, all anchoring
      elements showed a very unstable behaviour characterized by a varying marked
      increase and subsequent decrease in the retention force. During the ensuing
      functional period, the retention force followed a more stable course. In this
      phase, the frictional attachments having lamellae for activation proved more
      stable than did the spring-loaded retention attachments. Furthermore, in two of
      five cylindrical anchors by Gerber, the spring broke. This provides support to
      the concept that prefabricated attachments should be constructed as robust
      elements composed of as few individual parts as possible. This would help to
      ensure that service and repairs remain at a minimum. Frictional attachments with
      lamellae for activation are to be preferred for use in matrices and patrices over
      attachments having spring-loaded retention.

PMID- 12791151
TI  - Influence of fibre position on the flexural properties and strain energy of a
      fibre-reinforced composite.
AB  - The introduction of laboratory-processed composite systems and fibre
      reinforcement techniques have increased the possibilities for the prosthetic
      replacement of missing tooth tissues. Laboratory fabrication variables may
      significantly influence the properties of the final prosthesis. During the
      construction of a fibre-reinforced bridge it is necessary to place the fibre at
      some distance from the fitting surface of the restoration in the pontic region.
      No guidelines are available for optimal fibre placement in this respect. The
      purpose of this study was to assess the influence of placing ultra high molecular
      weight polyethylene (UHMWPE) fibre at five different distances from the tensile
      side of test samples on flexural properties and the strain energy stored within
      the dental composite. The results of this investigation showed that whilst moving
      the fibre reinforcement away from the tensile side by up to 1.5 mm led to a
      significant reduction in flexural strength, there was no significant decline in
      the increase in strain energy stored within the tested composite until this
      distance was exceeded.

PMID- 12791152
TI  - The effect of home-use fluoride gels on glass-ionomer, compomer and composite
      resin restorations.
AB  - The purpose of this study was to investigate the resistance to dissolution by two
      home-use fluoride gels on the surface integrity of glass-ionomer, resin modified
      glass-ionomer, compomer and composite resin restorations. Class V cavities
      prepared in extracted teeth were restored with a glass-ionomer (Fuji II), a resin
      modified glass-ionomer (Vitremenr), two compomers (Dyract and F-2000) and a
      composite resin (Z-100). Groups of five specimens of each material were treated
      for 24 h with one of the following: (i). distilled water, (ii). neutral fluoride
      gel and (iii). acidulated phosphate fluoride (APF) gel. Surface degradation of
      the restorations was studied using standard electron microscopy (SEM), rated
      according to specific criteria and statistically analysed by the Wilcoxon test
      (rank sums). Acidulated phosphate fluoride was found to have a significant effect
      on all examined materials, while minimal effects resulted from the neutral
      fluoride gel compared with the control group. The effect of home-use fluoride
      gels on glass-ionomer, compomer and composite resin restorations.

PMID- 12791153
TI  - Craniofacial morphology and obstructive sleep apnoea: a cephalometric analysis.
AB  - The craniofacial morphology of 31 male patients diagnosed with obstructive sleep
      apnoea syndrome (OSAS) and 37 healthy male subjects were compared using
      cephalometric evaluation of lateral skull radiographs. The aim was to evaluate
      which cephalometric variables related to craniofacial morphology discriminate
      between OSAS patients and non-OSAS subjects. Sixteen cephalometric measurements
      were determined to study the craniofacial morphology. Differences in
      cephalometric variables between the two groups were analysed with unpaired
      Student t-tests (significance level 0.05). A multiple regression analysis was
      used to evaluate the joint predictive value of selected variables. With regard to
      five variables, significant differences were observed between OSAS patients and
      non-OSAS subjects (P < 0.05). Data indicated a relatively anterior position of
      the maxilla, an increase of the mid-facial height and a more inferiorly located
      hyoid bone in the OSAS patient group. The multiple regression analysis yielded a
      model discriminating between OSAS patients and non-OSAS subjects, which included
      two hyoid bone variables and one related with the intermaxillary relationship. A
      causal relationship between cephalometric variables of craniofacial morphology
      and OSAS is not sufficiently supported by our data. Presumably, hyoid bone
      position is of predictive value in the cephalometric discrimination between OSAS
      patients and non-OSAS subjects.

PMID- 12791154
TI  - Effects of two vitamins, two growth factors and dexamethasone on the
      proliferation of rat bone marrow stromal cells and osteoblastic MC3T3-E1 cells.
AB  - The purpose of this investigation was to examine the effects of the addition of
      five cytokines such as vitamin C, vitamin D, bone morphogenetic protein (BMP),
      transforming growth factor-beta (TGF-beta) and dexamethasone (Dex) to Dulbecco's
      modified Eagle (DME) medium on the proliferation of Sprague-Dawley (SD) rats'
      bone marrow stromal cells and osteoblastic MC3T3-E1 cells by conducting 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For bone
      marrow stromal cells, vitamin C was needed for doubling the cell viability. While
      BMP, TGF-beta and vitamin D maintained the growth rate given by vitamin C, Dex
      with beta-glycerophosphate (beta-GP) slightly reduced this cell proliferation
      rate. For MC3T3-E1 cells, the addition of four cytokines examined (vitamin C,
      vitamin D, TGF-beta and BMP) did not significantly increase the cell
      proliferation while Dex with vitamin C and beta-GP slightly enlarged the cell
      proliferation. It can be pointed out that vitamin C in DME medium is
      indispensable for rapid proliferation of bone marrow stromal cells that contain
      many osteo-progenitor cells but is not effective for quick increase of
      osteoblastic MC3T3-E1 cells. This finding appears to contribute to tissue
      engineering therapy to fix bone and periodontal defects in dentistry.

PMID- 12791155
TI  - Effect of design of pre-fabricated posts and post heads on the retention of
      various cements and core materials.
AB  - The retention of new Para Post (PP) rounded undercut post head (PP-XT) was
      compared with the conventional flattened head (PP-P), using amalgam Dentacore and
      Synergy composite as core materials. The retention of the posts PP (passive
      serrated), PP-P (passive serrated with venting channels), PP-XP (passive, raised
      diamond-style pattern) and PP-XT (threaded on the coronal portion, and passive,
      raised diamond-shaped pattern on the apical portion), cemented with zinc
      phosphate cement (ZPC) or Duo Cement to extracted teeth, was evaluated. Tensile
      strength plots were recorded using an Instron instrument, while pulling the post
      and core in opposite directions. The following conclusions were drawn from this
      study: (i) The round undercut PP-XT head was more retentive than the PP-P head
      with both core materials. (ii) Amalgam was more retentive than Synergy with both
      head designs. (iii) PP-XT was the most retentive post to extracted tooth canals
      and PP-XP was the least retentive with either ZPC or Duo Cement. Post retention
      with (iv) ZPC in decreasing order of magnitude: PP-XT > PP-P > PP > PP-XP; and
      with Duo Cement: PP-XT > PP > PP-P > PP-XP - ZPC exhibited the highest retention
      of cemented posts.

PMID- 12791156
TI  - Analysis of kinesiograph recordings and masticatory efficiency after treatment of
      non-reducing disk displacement of the temporomandibular joint.
AB  - The purpose of this study was to clarify the kinesiographs of chewing movement
      and masticatory efficiency before and after treatment in patients with non
      reducing disk displacement of the temporomandibular joint (TMJ). Twenty patients
      who were diagnosed with unilateral non-reducing disk displacement of the TMJ were
      treated with pumping of the joint with injection of sodium hyaluronate. Chewing
      movement patterns in these patients were evaluated, using mandibular
      kinesiography (MKG) at their initial visit and at mean 19-month follow-up and the
      results were compared. Masticatory efficiency was also measured. As controls, 23
      volunteers without TMJ dysfunction were employed. Far from the results of normal
      volunteers, chewing movement patterns of the patients on MKG did not show
      deviation to the chewing side in the TMJ-unaffected-side chewing in the
      horizontal plane. However, such patterns of the patients became similar to those
      of normal volunteers after treatment. Masticatory efficiency of the patients
      improved after treatment, though it was impaired at initial visit. The MKG and
      masticatory efficiency test appeared to be a useful method of comparing
      masticatory function before and after treatment in patients with non-reducing
      disk displacement of the TMJ.

PMID- 12791157
TI  - Analysis of surface roughness of glass-ionomer cements and compomer.
AB  - The purpose of this study was to evaluate the surface roughness of two glass
      ionomer cements (Vitremer and Chelon-Fil), and one compomer (Dyract) when
      submitted to different finishing/polishing procedures at different times. A
      hundred 80-sample discs were made of each material and randomly divided into six
      finishing/polishing groups: mylar strip (control); Sof-Lex discs; diamond burs;
      diamond burs/Sof-Lex discs; 30-fluted carbide bur; 30-fluted carbide bur/Sof-Lex
      discs. These procedures were carried out immediately after preparation of the
      samples, after 24 and 168 h. Average surface roughness (Ra) was measured with a
      profilometer and the values were compared using anova (P < 0.05). The smoothest
      surface for all materials was obtained when cured in contact with the mylar
      strip. All other tested products increased surface roughness of restorative
      materials, but Sof-lex discs lead to better results. The worst results were
      verified with diamond burs. The finishing/polishing procedures, when performed
      immediately, can improve the roughness of glass-ionomer cements but not of the
      compomer tested.

PMID- 12791158
TI  - Masticatory performance: a protocol for standardized production of an artificial
      test food.
AB  - A protocol for standardizing the production of an artificial test food was
      established and its reliability was determined. An artificial test food was
      selected based on its superior properties compared with natural foods. The
      primary emphasis during production was the incorporation of all 3 cm of paste
      hardener and thoroughly kneading the material for 30 s. The curing process was
      studied to determine overall setting time. After at least 30 min, the physical
      properties of the test food were ready to be measured. The overall mean hardness
      of the test food was 489 +/- 60 load grams. Random error between operators was +/
      16 load grams while batches differed by +/-13 load grams and individual tablets
      differed by +/-15 load grams. This protocol provides a reliable standardized
      method for future masticatory performance studies.

PMID- 12791159
TI  - The effect of curing with plasma light on the shrinkage of dental restorative
      materials.
AB  - Commercially available light activated dental composites were used in this study
      to compare the shrinkage following curing with plasma light (Apollo95E, DMDS) and
      a convention halogen dental curing light (Prismetics Lite II, Dentsply).
      Polymerization shrinkage was determined by measuring the strain in one dimension
      by means of a contacting transducer. The percentage linear shrinkage were:
      Spectrum H = 1.84 + 0.31, P = 1.49 + 0.35*; Ana aesthetic H = 2.04 + 0.38, P =
      1.85 + 0.27; Esthet.x H = 1.66 + 0.28, P = 1.69 + 0.25; Dyract AP H = 2.39 +
      0.33, P = 2.18 + 0.35*; Apollo Restore H = 1.88 + 0.36, P = 1.42 + 0.33*; Surefil
      H = 0.88 + 0.28, P = 0.99 + 0.30 where * = significantly different, t-test at P <
      0.05. The results suggested that there was less shrinkage when curing some, but
      not all, materials using the plasma light, although this could be attributed to a
      reduced level of polymerization.

PMID- 12791160
TI  - Influence of filler loading on the two-body wear of a dental composite.
AB  - The purpose of the study was to explore the fundamental wear behaviour of a
      dental composite with different filler loadings under two-body wear conditions.
      The parent resin and filler components were mixed according to different weight
      ratios to produce experimental composites with filler loadings ranging from 20 to
      87.5% by weight. A two-body wear test was conducted on the experimental
      composites using a wear-testing machine. The machine was designed to simulate the
      impact of the direct cyclic masticatory loading that occurs in the occlusal
      contact area in vivo. The results showed that there was little increase in the
      rate of wear with filler loadings below 60 wt%, but a sharp increase between 80
      and 87.5 wt% in filler loading. Wide striations and bulk loss of material were
      apparent on the wear surfaces at higher filler loadings. Coefficients of friction
      increased with filler loading and followed the increase in rate of wear loss
      closely. It was concluded that, under two-body wear conditions, addition of high
      levels of filler particles into the resin matrix could reduce the wear resistance
      of dental composites. This finding may help when designing future dental
      composites for use in particular clinical settings.

PMID- 12791161
TI  - The condylar asymmetry measurements in different skeletal patterns.
AB  - In the present study, condylar asymmetry measurements were investigated on the
      lateral cephalometric head radiographs and the panoramic radiographs of 72
      subjects (36 males and 36 females), aged 12-16-years and having different
      skeletal patterns. The lateral cephalometric head radiographs were divided into
      three groups according to the ANB angle: ANB angles smaller than 1 degrees,
      between 1 degrees and 5 degrees, and larger than 5 degrees. In addition, each
      group was also divided into two subgroups according to sex. The effects on the
      ANB angle and sex on the condylar asymmetry measurement were investigated on the
      panoramic radiographs by means of variance analysis. It was observed that while
      condylar + ramus ratio measurement was affected by the change of ANB angle, the
      other measurements were not affected by it.

PMID- 12791162
TI  - Oral health in relation to wearing removable dentures provided by dentists,
      denturists and laboratory technicians.
AB  - The aim of this study was to evaluate the oral health of elderly Finnish men
      wearing removable dentures supplied either by dentists, denturists or laboratory
      technicians. From a sample of 550 men, 362 subjects were both interviewed and
      clinically examined. The subjects were asked a range of questions related to
      their oral health and dentures. Clinical examinations were carried out by one
      dentist using well-defined criteria and without knowing the information the
      respective subjects had given in the interview. The 242 denture wearers had a
      higher frequency (P < 0.001) of mucous membrane lesions (78.7%) than the 120 non
      wearers (27.5%). Differences between the denture providers were small, although
      subjects with dentures provided by dentists had less often most of the recorded
      mucous membrane lesions than other denture wearers. Coating of tongue and
      cheilitis angularis were the most commonly encountered lesions. High levels of
      yeast growth were observed more frequently (P < 0.02) among subjects who had
      obtained their dentures from dentists (41.3%) than from either denturists (17.1%)
      or laboratory technicians (18.2%). Among dentate subjects, the average number of
      remaining teeth was higher (P < 0.05) among those who had obtained their dentures
      from dentists (8.7) than among subjects wearing dentures from denturists (5.9) or
      laboratory technicians (6.2). Subjects wearing dentures supplied by dentists had
      slightly better oral health than other denture wearers. The observed differences
      can be at least partly explained by dentists' patients having higher number of
      remaining teeth and also more frequent check-up visits.

PMID- 12791163
TI  - The effect of disinfectant solutions on the hardness of acrylic resin denture
      teeth.
AB  - This investigation studied the effects of disinfectant solutions on the hardness
      of acrylic resin denture teeth. The occlusal surfaces of 64 resin denture teeth
      were ground flat with abrasives up to 400-grit silicon carbide paper.
      Measurements were made after polishing and after the specimens were stored in
      water at 37 degrees C for 48 h. The specimens were then divided into four groups
      and immersed in chemical disinfectants (4% chlorhexidine; 1% sodium hypochlorite
      and sodium perborate) for 10 min. The disinfection methods were performed twice
      to simulate clinical conditions and hardness measurements were made. Specimens
      tested as controls were immersed in water during the same disinfection time.
      Eight specimens were produced for each group. After desinfection procedures,
      testing of hardness was also performed after the samples were stored at 37
      degrees C for 7, 30, 60, 90 and 120 days. Data were analysed using two-way
      analysis of variance (anova) and Tukey's test at 95% confidence level. According
      to the results, no significant differences were found between materials and
      immersion solutions (P > 0.05). However, a continuous decrease in hardness was
      noticed after ageing (P < 0.05). It was conclude that the surfaces of both
      acrylic resin denture teeth softened upon immersion in water regardless the
      disinfecting solution.

PMID- 12791165
TI  - Effect of ceramic surface treatment on the shear bond strengths of two resin
      luting agents to all-ceramic materials.
AB  - The purpose of this study was to evaluate the bond strengths of some resin luting
      cements of two different all ceramic materials (In-Ceram, IPS-Empress). Composite
      cylinders 3.2 x 2 mm were prepared on the ceramic surfaces for a shear test. Four
      ceramic surface treatments were performed. (i). As received, (ii). grinding with
      diamond bur, (iii). sandblasting with 50 microm alumina grit and (iv). HF acid
      treatment and sandblasting with 50 microm alumina grit. Ceramic specimens were
      treated with one of the four methods and then cemented together with each of the
      two luting agents. The tested luting cements were Panavia F and Clearfil Se Bond
      (CSeB). The CSeB demonstrated the highest bond strength (59.95 MPa) regardless of
      the ceramic blocks. The average of load to fracture the In-Ceram blocks luted
      with Panavia F cement was 25.89 MPa. The mean shear bond strength of IPS Empress
      blocks luted with Panavia F cement was 10.31 MPa. Grinding the surface with a
      diamond bur for In-Ceram blocks luted with Panavia-F was 30.93 MPa and with CSeB
      was 77.04 MPa. For IPS-Empress blocks these values decreased to 12.39 MPa for
      Panavia-F and 30.84 MPa for CSeB. Acid etching of the surfaces with HF acid
      demonstrated a weak tendency to improve bond strength (In-Ceram-->Panavia-F=
      14.59 MPa and CSeB=59.32 Mpa; IPS-Empress--> Panavia-F=5.85 MPa and CSeB= 23.33
      MPa).

PMID- 12791164
TI  - A new silicon-based root canal sealer (Roekoseal-Automix).
AB  - This study evaluated the new silicon-based sealer 'Roekoseal-Automix' (RSA) with
      respect to sealing, bonding capabilities and biocompatibility with rat
      subcutaneous connective tissue. For the microleakage study, 36 single rooted
      teeth were instrumented and 30 of these obturated with either Grossman's sealer
      or RSA using lateral condensation technique (15 of each). Six teeth were not
      obturated and used as control group. For investigating bonding capability, 10 of
      the obturated roots with RSA and Grossman's sealer were ground and split
      longitudinally and examined by scanning electron microscopy (SEM). The RSA was
      found to seal significantly better than Grossman's sealer. The SEM examination
      revealed a good bond between RSA and the dentine and between RSA and the gutta
      percha. Tissue reaction was evaluated by injecting 0.1 mL RSA into the connective
      tissue of 21 male Albino-Wistar rats and observing at 24 h, 7 days and 30 days
      and 30 days. Formation of a new granulation tissue with fibrous tissue adjacent
      to the material at 30 days. This study found that RSA performed well.

PMID- 12791166
TI  - Piperacillin induced bone marrow suppression: a case report.
AB  - BACKGROUND: Piperacillin (and piperacillin/tazobactam) is a commonly prescribed
      antibiotic and is generally considered safe. We report a case of piperacillin
      induced bone marrow suppression. CASE PRESENTATION: A 19-year-old boy was being
      treated with piperacillin followed by piperacillin/tazobactam for infected
      pancreatic pseudocyst. After 21 days of treatment, he developed neutropenia and
      thrombocytopenia. These reversed promptly after stopping piperacillin/tazobactam.
      The time course of events suggested that piperacillin was the cause of bone
      marrow suppression in this patient. CONCLUSION: Bone marrow suppression is a
      serious adverse effect of piperacillin, which should be kept in mind while
      treating patients with this drug.

PMID- 12791167
TI  - Mediastinitis complicating a percutaneous endoscopic gastrostomy: a case report.
AB  - BACKGROUND: Since its introduction in the early 1980s, percutaneous endoscopic
      gastrostomy has become the most popular method for performing a gastrostomy for
      long-term enteral feeding. It has been associated, however, with a lot of minor
      and major complications. CASE PRESENTATION: A case of mediastinitis with
      concominant sepsis caused by a masked esophageal perforation after percutaneous
      endoscopic gastrostomy in a multi-traumatized, brain-injured patient is
      presented. Ten - fourteen days after the procedure, the patient became febrile
      and gradually septic with tenderness of the sternum and upper abdomen.
      Computerized tomography of the thorax revealed mediastinitis. An urgent left
      thoracotomy and laparotomy were performed for drainage of the mediastinum,
      removal of the gastrostomy and insertion of a jejunostomy tube. The patient
      improved soon after the surgery. He was successfully weaned off the ventilator
      and was discharged from the Intensive Care Unit. CONCLUSION: Perforating
      mediastinitis is a rare but potentially lethal complication of percutaneous
      endoscopic gastrostomy. When diagnosed and properly treated it may have a
      favourable outcome.

PMID- 12791169
TI  - The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes.
AB  - BACKGROUND: Flobufen (F) is an original nonsteroidal anti-inflammatory drug with
      one center of chirality. 4-Dihydroflobufen (DHF), compound with two chiral
      centers, is the main metabolite of F in microsomes and cytosol in all standard
      laboratory animals. This work describes the biotransformation of F enantiomers
      and DHF stereoisomers in isolated male guinea pig hepatocytes. Guinea pigs were
      chosen with respect to similarities in F metabolism as in Man found earlier. R-F,
      S-F, (2R;4S)-DHF, (2S;4R)-DHF, (2S;4S)-DHF and (2R;4R)-DHF, structurally very
      similar compounds, served as substrates in order to observe their interaction
      with enzymes. Stereospecificity of the respective enzymes was studied in vitro,
      using hepatocytes monolayer. Chiral HPLC using R,R-ULMO column as chiral
      stationary phase was used for detection and quantitation of metabolites. RESULTS:
      (2R;4S)-DHF and (2S;4S)-DHF were the principle stereoisomers detected after
      incubation with rac-F, R-F and S-F. The ratio of (2R;4S)-DHF/(2S;4S)-DHF ranged
      from 1.1 to 2.4 depending on the substrate used. (2R;4S)-DHF was the major
      stereoisomer found after incubation with (2S;4S)-DHF and (2R;4R)-DHF. (2S;4S)-DHF
      was the principle stereoisomer found after incubation with (2R;4S)-DHF and
      (2S;4R)-DHF. Besides DHF stereoisomers, other metabolites (M-17203, UM-1 and UM
      2) were also detected after incubation of hepatocytes monolayer with F.
      Interestingly, these metabolites were not found in incubation of all F forms and
      DHF with fresh liver homogenate. CONCLUSIONS: Different activities and
      stereospecificities of the respective enzymes were observed for each substrate in
      primary culture of hepatocytes. Cell integrity is crucial for formation of
      secondary metabolites M-17203, UM-1 and UM-2.

PMID- 12791168
TI  - A national survey on the patterns of treatment of inflammatory bowel disease in
      Canada.
AB  - BACKGROUND: There is a general lack of information on the care of inflammatory
      bowel disease (IBD) in a broad, geographically diverse, non-clinic population.
      The purposes of this study were (1) to compare a sample drawn from the membership
      of a national Crohn's and Colitis Foundation to published clinic-based and
      population-based IBD samples, (2) to describe current patterns of health care
      use, and (3) to determine if unexpected variations exist in how and by whom IBD
      is treated. METHODS: Mailed survey of 4453 members of the Crohn's and Colitis
      Foundation of Canada. The questionnaire, in members stated language of
      preference, included items on demographic and disease characteristics, general
      health behaviors and current and past IBD treatment. Each member received an
      initial and one reminder mailing. RESULTS: Questionnaires were returned by 1787,
      913, and 128 people with Crohn's disease, ulcerative colitis and indeterminate
      colitis, respectively. At least one operation had been performed on 1159 Crohn's
      disease patients, with risk increasing with duration of disease. Regional
      variation in surgical rates in ulcerative colitis patients was identified. 6
      mercaptopurine/azathioprine was used by 24% of patients with Crohn's disease and
      12% of patients with ulcerative colitis (95% CI for the difference: 8.9%-15%). In
      patients with Crohn's disease, use was not associated with gender, income or
      region of residence but was associated with age and markers of disease activity.
      Infliximab was used by 112 respondents (4%), the majority of whom had Crohn's
      disease. Variations in infliximab use based on region of residence and income
      were not seen. Sixty-eight percent of respondents indicated that they depended
      most on a gastroenterologist for their IBD care. There was significant regional
      variation in this. However, satisfaction with primary physician did not depend on
      physician type (for example, gastroenterologist versus general practitioner).
      CONCLUSION: This study achieved the goal of obtaining a large, geographically
      diverse sample that is more representative of the general IBD population than a
      clinic sample would have been. We could find no evidence of significant regional
      variation in medical treatments due to gender, region of residence or income
      level. Differences were noted between different age groups, which deserves
      further attention.

PMID- 12791170
TI  - Sexual selection on land snail shell ornamentation: a hypothesis that may explain
      shell diversity.
AB  - BACKGROUND: Many groups of land snails show great interspecific diversity in
      shell ornamentation, which may include spines on the shell and flanges on the
      aperture. Such structures have been explained as camouflage or defence, but the
      possibility that they might be under sexual selection has not previously been
      explored. PRESENTATION OF THE HYPOTHESIS: The hypothesis that is presented
      consists of two parts. First, that shell ornamentation is the result of sexual
      selection. Second, that such sexual selection has caused the divergence in shell
      shape in different species. TESTING THE HYPOTHESIS: The first part of the
      hypothesis may be tested by searching for sexual dimorphism in shell
      ornamentation in gonochoristic snails, by searching for increased variance in
      shell ornamentation relative to other shell traits, and by mate choice
      experiments using individuals with experimentally enhanced ornamentation. The
      second part of the hypothesis may be tested by comparing sister groups and
      correlating shell diversity with degree of polygamy. IMPLICATIONS OF THE
      HYPOTHESIS: If the hypothesis were true, it would provide an explanation for the
      many cases of allopatric evolutionary radiation in snails, where shell diversity
      cannot be related to any niche differentiation or environmental differences.

PMID- 12791171
TI  - Poly: a quantitative analysis tool for simple sequence repeat (SSR) tracts in
      DNA.
AB  - BACKGROUND: Simple sequence repeats (SSRs), microsatellites or polymeric
      sequences are common in DNA and are important biologically. From mononucleotide
      to trinucleotide repeats and beyond, they can be found in long (> 6 repeating
      units) tracts and may be characterized by quantifying the frequencies in which
      they are found and their tract lengths. However, most of the existing computer
      programs that find SSR tracts do not include these methods. RESULTS: A computer
      program named Poly has been written not only to find SSR tracts but to analyze
      the results quantitatively. CONCLUSIONS: Poly is significant in its use of non
      standard, quantitative methods of analysis. And, with its flexible object model
      and data structure, Poly and its generated data can be used for even more
      sophisticated analyses.

PMID- 12791172
TI  - Putative hAPN receptor binding sites in SARS_CoV spike protein.
AB  - AIM: To obtain the information of ligand-receptor binding between the S protein
      of SARS-CoV and CD13, identify the possible interacting domains or motifs related
      to binding sites, and provide clues for studying the functions of SARS proteins
      and designing anti-SARS drugs and vaccines. METHODS: On the basis of comparative
      genomics, the homology search, phylogenetic analyses, and multi-sequence
      alignment were used to predict CD13 related interacting domains and binding sites
      in the S protein of SARS-CoV. Molecular modeling and docking simulation methods
      were employed to address the interaction feature between CD13 and S protein of
      SARS-CoV in validating the bioinformatics predictions. RESULTS: Possible binding
      sites in the SARS-CoV S protein to CD13 have been mapped out by using
      bioinformatics analysis tools. The binding for one protein-protein interaction
      pair (D757-R761 motif of the SARS-CoV S protein to P585-A653 domain of CD13) has
      been simulated by molecular modeling and docking simulation methods. CONCLUSION:
      CD13 may be a possible receptor of the SARS-CoV S protein, which may be
      associated with the SARS infection. This study also provides a possible strategy
      for mapping the possible binding receptors of the proteins in a genome.

PMID- 12791173
TI  - Identification of probable genomic packaging signal sequence from SARS-CoV genome
      by bioinformatics analysis.
AB  - AIM: To predict the probable genomic packaging signal of SARS-CoV by
      bioinformatics analysis. The derived packaging signal may be used to design
      antisense RNA and RNA interfere (RNAi) drugs treating SARS. METHODS: Based on the
      studies about the genomic packaging signals of MHV and BCoV, especially the
      information about primary and secondary structures, the putative genomic
      packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi
      alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV
      and HCoV 229E. Secondary structures of RNA sequences were also predicted for the
      identification of the possible genomic packaging signals. Meanwhile, the N and M
      proteins of all five viruses were analyzed to study the evolutionary relationship
      with genomic packaging signals. RESULTS: The putative genomic packaging signal of
      SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the
      most variable region of this gene. The RNA secondary structure of SARS-CoV
      genomic packaging signal is very similar to that of MHV and BCoV. The same result
      was also obtained in studying the genomic packaging signals of PEDV and HCoV
      229E. Further more, the genomic sequence multi-alignment indicated that the
      locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other.
      It seems that the mutation rate of packaging signal sequences is much higher than
      the N protein, while only subtle variations for the M protein. CONCLUSIONS: The
      probable genomic packaging signal of SARS-CoV is analogous to that of MHV and
      BCoV, with the corresponding secondary RNA structure locating at the similar
      region of ORF1b. The positions where genomic packaging signals exist have
      suffered rounds of mutations, which may influence the primary structures of the N
      and M proteins consequently.

PMID- 12791174
TI  - A 3D model of SARS_CoV 3CL proteinase and its inhibitors design by virtual
      screening.
AB  - AIM: To constructed a three-dimensional (3D) model for the 3C like (3CL)
      proteinase of SARS coronavirus (SARS-CoV), and to design inhibitors of the 3CL
      proteinase based on the 3D model. METHODS: Bioinformatics analyses were performed
      to search the homologous proteins of the SARS-CoV 3CL proteinase from the GenBank
      and PDB database. A 3D model of the proteinase was constructed by using homology
      modeling technique. Targeting to the 3D model and its X-ray crystal structure of
      the main proteinase (Mpro) of transmissible gastroenteritis virus (TGEV), virtual
      screening was performed employing molecular docking method to identify possible
      3CL proteinase inhibitors from small molecular databases. RESULTS: Sequence
      alignment indicated that the SARS-CoV 3CL proteinase was extremely homologous to
      TGEV Mpro, especially the substrate-binding pocket (active site). Accordingly, a
      3D model for the SARS-CoV 3CL proteinase was constructed based on the crystal
      structure of TGEV Mpro. The 3D model adopts a similar fold of the TGEV Mpro, its
      structure and binding pocket feature are almost as same as that of TGEV Mpro. The
      tested virtual screening indicated that 73 available proteinase inhibitors in the
      MDDR database might dock into both the binding pockets of the TGEV Mpro and the
      SARS-CoV 3CL proteinase. CONCLUSIONS: Either the 3D model of the SARS-CoV 3CL
      proteinase or the X-ray crystal structure of the TGEV Mpro may be used as a
      starting point for design anti-SARS drugs. Screening the known proteinase
      inhibitors may be an appreciated shortcut to discover anti-SARS drugs.

PMID- 12791175
TI  - Small envelope protein E of SARS: cloning, expression, purification, CD
      determination, and bioinformatics analysis.
AB  - AIM: To obtain the pure sample of SARS small envelope E protein (SARS E protein),
      study its properties and analyze its possible functions. METHODS: The plasmid of
      SARS E protein was constructed by the polymerase chain reaction (PCR), and the
      protein was expressed in the E coli strain. The secondary structure feature of
      the protein was determined by circular dichroism (CD) technique. The possible
      functions of this protein were annotated by bioinformatics methods, and its
      possible three-dimensional model was constructed by molecular modeling. RESULTS:
      The pure sample of SARS E protein was obtained. The secondary structure feature
      derived from CD determination is similar to that from the secondary structure
      prediction. Bioinformatics analysis indicated that the key residues of SARS E
      protein were much conserved compared to the E proteins of other coronaviruses. In
      particular, the primary amino acid sequence of SARS E protein is much more
      similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses.
      The transmembrane (TM) segment of the SARS E protein is relatively more conserved
      in the whole protein than other regions. CONCLUSION: The success of expressing
      the SARS E protein is a good starting point for investigating the structure and
      functions of this protein and SARS coronavirus itself as well. The SARS E protein
      may fold in water solution in a similar way as it in membrane-water mixed
      environment. It is possible that beta-sheet I of the SARS E protein interacts
      with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a
      random structure in water solution.

PMID- 12791177
TI  - Horizontal gene transfer-emerging multidrug resistance in hospital bacteria.
AB  - The frequency and spectrum of antibiotic resistant infections have increased
      worldwide during the past few decades. This increase has been attributed to a
      combination of microbial characteristics, the selective pressure of antimicrobial
      use, and social and technical changes that enhance the transmission of resistant
      organisms. The resistance is acquired by mutational change or by the acquisition
      of resistance-encoding genetic material which is transferred from another
      bacteria. The spread of antibiotic resistance genes may be causally related to
      the overuse of antibiotics in human health care and in animal feeds, increased
      use of invasive devices and procedures, a greater number of susceptible hosts,
      and lapses in infection control practices leading to increased transmission of
      resistant organisms. The resistance gene sequences are integrated by
      recombination into several classes of naturally occurring gene expression
      cassettes and disseminated within the microbial population by horizontal gene
      transfer mechanisms: transformation, conjugation or transduction. In the
      hospital, widespread use of antimicrobials in the intensive care units (ICU) and
      for immunocompromised patients has resulted in the selection of multidrug
      resistant organisms. Methicillin-resistant Staphylococci, vancomycin resistant
      Enterococci and extended-spectrum beta-lactamase (ESBL) producing Gram negative
      bacilli are identified as major problem in nosocomial infections. Recent
      surveillance studies have demonstrated trend towards more seriously ill patients
      suffering from multidrug-resistant nosocomial infections. Emergence of
      multiresistant bacteria and spread of resistance genes should enforce the
      application of strict prevention strategies, including changes in antibiotic
      treatment regimens, hygiene measures, infection prevention and control of
      horizontal nosocomial transmission of organisms.

PMID- 12791176
TI  - Alzheimer-like phosphorylation of tau and neurofilament induced by cocaine in
      vivo.
AB  - AIM: To explore the relationship between cocaine-induced cyclin-dependent kinase
      5 (CDK5) overexpression or overactivation and Alzheimer-like hyperphosphorylation
      of cytoskeletal protein. METHODS: Cocaine was injected (ip, 20 mg/kg/d) into rats
      and the phosphorylation of neuronal cytoskeletal proteins was measured by Western
      blotting. RESULTS: The levels of phosphorylated tau at PHF-1 epitope and
      phosphorylated neurofilament determined by SMI31 were elevated in rat brain
      hippocampus, cortex, and caudatoputamen on d 8 and d 16 after the injection of
      cocaine, when compared with saline control rat at the same brain regions. On the
      other hand, the levels of tau non-phosphorylated at tau-1 site and non
      phosphorylated neurofilament determined by SMI32 were decreased in same brain
      regions at the same time points examined. No significant difference of
      phosphorylated tau and neurofilament at those epitopes was seen on d 4. Although
      cocaine injection could induce significant hyperphosphorylation of neuronal
      cytoskeletal proteins, the overexpression of CDK5 and p35 was not detected.
      CONCLUSION: Peritoneal injection of cocaine induces Alzheimer-like
      hyperphosphorylation of tau and neurofilament in rat brain, and the effect may be
      not relevant to an increase in overexpression or overactivation of CDK5.

PMID- 12791178
TI  - Iptkalim inhibits cocaine challenge-induced enhancement of dopamine levels in
      nucleus accumbens and striatum of rats by up-regulating Kir6.1 and Kir6.2 mRNA
      expression.
AB  - AIM: To investigate the effect and mechanism of novel ATP-sensitive potassium
      channel opener (KCO) iptkalim (IPT) on acute and cocaine challenge-induced
      alterations in the levels of dopamine (DA) and glutamate (Glu) from nucleus
      accumbens (NAc), striatum, and prefrontal cortex (PFC) in rats. METHODS: The
      levels of DA and Glu were assayed using high performance liquid chromatography
      (HPLC) combined with amperometric and fluorescent detection, respectively. The
      mRNA levels of Kir6.1, Kir6.2, SUR1, and SUR2 were measured by semiquantitative
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: IPT did not
      affect acute cocaine (30 mg/kg, ip)-induced elevations in either DA levels from
      NAc and striatum or Glu levels from NAc and PFC. An acute cocaine challenge (30
      mg/kg, ip) on d 21 after withdrawal caused an elevation in DA levels in NAc and
      striatum. Moreover, the same treatment also increased Glu levels in PFC and NAc
      of cocaine-pretreated rats. Repeated IPT injections reversed cocaine challenge
      induced DA increase in NAc and striatum. Cocaine challenge increased Kir6.1 and
      Kir6.2 mRNA expression in striatum and NAc and only elevate Kir6.2 expression in
      PFC in both cocaine-pretreated rats and rats pretreated with IPT plus cocaine.
      Moreover, expression of Kir6.1 and Kir6.2 mRNA was augmented in rats pretreated
      with IPT plus cocaine compared to rats pretreated with cocaine alone. No
      significant change was found in the SUR1 and SUR2 expression of all four groups.
      CONCLUSION: IPT inhibited cocaine challenge-induced enhancement of DA levels in
      NAc and striatum by up-regulating Kir6.1 and Kir6.2 mRNA expression.

PMID- 12791179
TI  - High glucose enhance expression of matrix metalloproteinase-2 in smooth muscle
      cells.
AB  - AIM: To investigate the effects of high glucose on expression of matrix
      metalloproteinase-2 (MMP-2) in rat aortic smooth muscle cells and the influence
      of matrix remodeling on atherogenesis in diabetic patients. METHODS: The smooth
      muscle cells were cultured from the thoracic aorta of Sprague-Dawley (SD) rat.
      MMP-2 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT
      PCR), MMP-2 protein was measured by Western blotting, and MMP-2 activity in
      conditioned medium was observed by zymography. RESULTS: In comparison with the
      control, there was no difference in the expression of MMP-2 when glucose
      concentration was 1 g/L, whereas MMP-2 activity in smooth muscle cells was
      significantly increased by the glucose 5 g/L (P<0.01). CONCLUSION: High glucose
      enhanced the expression and activity of MMP-2 in smooth muscle cells, which may
      provide an explanation for the phenomenon that diabetes patients are prone to
      have atherosclerotic lesions.

PMID- 12791180
TI  - Activation of c-Jun and suppression of phospho-p44/42 were involved in
      diphenylhydantoin-induced apoptosis of cultured rat cerebellar granule neurons.
AB  - AIM: To investigate possible intracellular signal molecules involved in
      diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN)
      and explore possible molecular mechanisms of neurotoxicity of DPH. METHODS:
      Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel
      electrophoresis were used to test morphological and biological characters of
      primary CGN and cortical neurons (CN) in the presence or absence of 100
      micromol/L DPH; Western blot and RT-PCR were employed to further investigate
      apoptotic/survival signal moleculars involved in the neuronal apoptotic signal
      transdution. RESULTS: DPH 100 micromol/L induced a typical apoptosis of CGN but
      had no toxicity on CN. Cerebellar granule neural apoptosis induced by 100
      micromol/L DPH was significantly inhibited by pre-treatment with SB203580 (10
      micromol/L) or CEP-11004 (1 micromol/L) for 1 h. DPH markedly upregulated the
      levels of phospho-c-Jun (active c-Jun), total c-Jun protein and c-jun mRNA in
      CGN. The levels of phospho-c-Jun dramatically elevated by DPH at 8 h were
      significantly inhibited by SB203580 (10 micromol/L) or CEP-11004 (1 micromol/L).
      Moreover, the activities of p44/42 (ERK1/ERK2), other members of MAP kinases and
      generally believed to be important survival effetors in CGN, were markedly
      suppressed. However, the activities of both JNK and p38 were little affected in
      the process of apoptosis of CGN induced by 100 micromol/L DPH. CONCLUSION: The
      selective toxicity of DPH on CGN is likely due to its ability to induce apoptosis
      of CGN, it is a process involved activation of c-Jun and suppression of the
      activity of p44/42.

PMID- 12791181
TI  - Characterization of cAMP accumulation mediated by three alpha1-adrenoceptor
      subtypes in HEK293 cells.
AB  - AIM: To investigate the characterization of cAMP response mediated by alpha1
      adrenoceptor (alpha1-AR) subtypes in HEK293 cells. METHODS: (1) Full-length cDNA
      encoding three alpha1-AR subtypes were transfected into HEK293 cells by the
      calcium phosphate precipitation method, respectively. (2) The densities of alpha1
      AR subtypes expressed in HEK293 cells were measured by radioligand binding assay.
      (3) cAMP accumulation was measured by [3H]adenine prelabeling method. RESULTS:
      (1) Activation of each of three subtypes resulted in an increase of cAMP
      accumulation in HEK293 cells in a dose-dependent manner, which was inhibited by
      selective alpha1-AR antagonist prazosin. (2) Comparing the pharmacological
      property, the maximal responses of alpha1A-AR to agonists were the most potent,
      while the sensitivity of alpha1-AR subtypes to norepinephrine (NE) was the
      highest. CONCLUSION: Each of three alpha1-AR subtypes can mediate cAMP
      accumulation in HEK293 cell line, and there are differences in pharmacological
      property.

PMID- 12791182
TI  - Ca2+ sparks evoked by depolarization of rat ventricular myocytes involve multiple
      release sites.
AB  - AIM: To investigate the fundamental nature of calcium release events (Ca2+
      "sparks") evoked in rat ventricular myocytes during excitation-contraction (E-C)
      coupling. METHODS: High-resolution line-scan confocal imaging with the
      fluorescent calcium indicator and patch-clamp techniques were used to study the
      spontaneous Ca2+ sparks and sparks evoked by depolarization. RESULTS: 1) Line
      scans oriented along the length of the cell showed that both spontaneous sparks
      and sparks evoked by depolarization to -35 mV appeared to arise at single sites
      spacing about 1.8 microm apart (ie, the sarcomere length), and measurements of
      their longitudinal spread (full-width at half-maximal amplitude: FWHM) followed
      single Gaussian distributions with means of 2.6 microm. 2) Different to this,
      transverse line scans often revealed spontaneous and evoked sparks that appeared
      to arise near-synchronously from paired sites. Measurements of transverse FWHM of
      both spontaneous and evoked sparks showed bimodal distributions, which were fit
      well by the sums of two Gaussian curves with means of 1.8 and 2.9 microm for
      spontaneous sparks and with means of 1.9 and 3.1 microm for evoked sparks.
      Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1,
      respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca2+ sparks evoked
      by depolarization are not "unitary" events, but often involve multiple sites of
      origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca2+
      released during sparks directly triggered by influx through L-type Ca2+ channels
      may, in turn, trigger neighboring sites. The restricted involvement of only a few
      transverse release sites preserves the essential feature of the "local control"
      theory of E-C coupling.

PMID- 12791183
TI  - Endothelin-1 promoted proliferation of vascular smooth muscle cell through
      pathway of extracellular signal-regulated kinase and cyclin D1.
AB  - AIM: To investigate whether endothelin-1 (ET-1) can promote human umbilical
      artery smooth muscle cell (HUASMC) proliferation through pathway of extracellular
      signal-regulated kinase (ERK) and cyclin D1. METHODS: The effects of ET-1 and
      PD98059 on HUASMC were evaluated by MTT assay. The content of DNA was defined by
      [3H]TdR assay and cell cycle was analyzed by flow cytomerty. Western blot
      analysis was employed to detect the active phosphorylated state of ERK and the
      expression of cylin D1. RESULTS: Firstly, ET-1 (100 nmol/L) stimulated HUASMC
      proliferation compared with the group without ET-1 (P<0.05) and PD98059 group
      (P<0.05). PD98059 inhibited the HUASMC proliferation stimulated by ET-1 (P<0.05).
      Secondly, ET-1 stimulated DNA synthesis of HUASMC compared with the group without
      ET-1 (P<0.05). Thirdly, ET-1 promoted the cell cycle transition from G0/G1 phase
      to S phase. G0/G1 phase cell percentage was obviously decreased compared with the
      group without ET-1 (P<0.05). S phase cell percentage was increased compared with
      the group without ET-1 (P<0.05). Fourthly, ET-1 increased the phosphorylated
      level of ERK and the expression of cylin D1, an inhibitor of ERK blocked
      phosphorylated level of ERK and cyclin D1 expression. ERK phosphorylated level of
      ET-1 group was evidently increased compared with PD98059 group (P<0.05), Cyclin
      D1 protein expression also was increased compared with PD98059 group (P<0.05).
      While nonphosphorylated ERK expression remained unchanged. CONCLUSION: Endothelin
      1 promoted vascular smooth muscle cell proliferation through pathway of ERK and
      cyclin D1.

PMID- 12791185
TI  - Metabolism of SFZ-47 in chicken embryo by liquid chromatography-electrospray ion
      trap mass spectrometry.
AB  - AIM: To develop an alternative method for investigation of drug metabolism by
      fertilized chicken eggs using 3H-1,2-dihydro-2-(4-methyl-phenylamino) methyl-1
      pyrrolizinone (SFZ-47) as a probe drug. METHODS: SFZ-47 (15 mg) was injected into
      the albumen of eggs from standardized breed chickens previously incubated for 10
      d. After 72 h of further incubation, the allantoic liquid was subjected to solid
      phase extraction on XAD-2 columns and analyzed by liquid chromatography
      electrospray ion trap mass spectrometry method. RESULTS: Three major metabolites
      were identified, namely 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino) benzyl
      alcohol (SFZ-47-OH), 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino)-benzoic
      acid (SFZ-47-COOH), and its glucuronide conjugates. The metabolic profile was
      little different from that previously found in rabbits and dogs. CONCLUSION: The
      result demonstrates the usefulness of the fertilized chicken egg as a convenient
      source of both phase I and phase II metabolites for further metabolism studies of
      SFZ-47.

PMID- 12791184
TI  - Lipolysis and apoptosis of adipocytes induced by neuropeptide Y-Y5 receptor
      antisense oligodeoxynucleotides in obese rats.
AB  - AIM: To investigate the influence of central administration of neuropeptide Y-Y5
      receptor antisense oligodeoxynucleotides (ODN) on the body weight and fat pads of
      high-energy diet-induced obese rats, and the effects on white adipocyte lipolysis
      and apoptosis. METHODS: Y5 receptor antisense, sense, mismatched
      oligodeoxynucleotides (ODN) or vehicle were intracerebroventricularly injected,
      and average adipocyte area was calculated. DNA ladders were measured to evaluate
      adipocyte apoptosis, and RT-PCR was used to analyze the expression of bcl-2 and
      bax gene. RESULTS: (1) Central administration of Y5 receptor antisense ODN
      significantly decreased body weight, fat pads, and average adipocyte area. (2)
      DNA fragmentation was presented after electrophoresis at both epididymal and
      retroperitoneal adipose tissue. (3) The expression of bcl-2 gene was
      downregulated, while the expression of bax was upregulated. CONCLUSION: Lipolysis
      and adipocyte apoptosis may be important reasons for Y5 receptor antisense
      therapy.

PMID- 12791186
TI  - Population pharmacokinetics of propofol in Chinese patients.
AB  - AIM: To analyze population pharmacokinetics of propofol in Chinese surgical
      patients using a nonlinear mixed-effect model (NONMEM) program and to quantitate
      the effects of covariance of gender, age, and body weight. METHODS: The
      population pharmacokinetics of propofol was investigated in 76 selective surgical
      patients (37 males and 39 females aged 19-77 a, weighing 39-86 kg). A total of
      1439 blood samples were analyzed using NONMEM (NONMEM Project Group, University
      of California, San Francisco, CA). Interindividual variability was estimated for
      clearances and distribution volumes. The effects of age, body weight, and gender
      were investigated. RESULTS: The pharmacokinetics of propofol in Chinese patients
      was best described by a three-compartment pharmacokinetic model. Body weight was
      found to be a significant factor for the elimination clearance, the two inter
      compartmental clearances, and the volume of the central compartment. The volumes
      of the shallow peripheral compartment and deep peripheral compartment remain
      constant for all individuals. The estimates of these parameters for a 60-kg adult
      were 1.56 L/min, 0.737 L/min, 0.360 L/min, 12.1 L, 43 L, and 213 L, respectively.
      For old patients, the elimination clearance and volume of the central compartment
      decreased. CONCLUSION: The pharmacokinetics of propofol in Chinese patients can
      be well described by a standard three-compartment pharmacokinetic model.
      Inclusion of age and body weight as covariances significantly improved the model.
      Adjusting pharmacokinetics to the individual patients should improve the
      precision of target-controlled infusion system.

PMID- 12791187
TI  - Pharmacokinetics and tissue distribution of iv injection of polyphase liposome
      encapsulated cisplatin (KM-1) in rats.
AB  - AIM: The pharmacokinetics and biodistribution of cisplatin encapsulated in
      polyphase liposome (KM-1) were compared with those of free drug in rats. METHODS:
      The platinum levels in serum and normal organs, after a single dose of iv
      injection of free or encapsulated cisplatin to rats, were determined by induced
      coupled plasma atomic emission spectrometry. RESULTS: Serum platinum
      concentration-time curve after a single iv dose of KM-1 4.5 mg/kg in rats was
      fitted with an open three-compartment model. The pharmacokinetic parameters were
      as follows: Vc=0.10 L/kg, T1/2pai=0.3 h, T1/2alpha=3.5 h, T1/2beta=2.7 h, AUC=265
      mg.h.L(-1), and CL(s) =0.02 g.L.h(-1). KM-1 was cleared from the circulation much
      more slowly than free cisplatin. Liver and spleen had the highest concentration
      of platinum after KM-1 treatment. CONCLUSION: KM-1 remained in the bloodstream
      longer than its free drug, and was taken mainly by the reticuloendothelial
      system.

PMID- 12791188
TI  - A protein in pig spleen similar to immune suppressive protein of stress.
AB  - AIM: To purify a protein in pig spleens, which was similar to immune suppressive
      protein of stress (ISPS), and characterize its properties and functions. METHODS:
      1) Pig spleen was extracted in dilute hydrochloric acid. 2) The extract was ultra
      filtrated for having high molecular weight proteins (Mr>30 000). 3) The filtrates
      were purified with FPLC affinity chromatography. 4) The elute from FPLC was used
      for T-lymphocyte proliferation and ELISA test. 5) Lastly, SDS-PAGE was used to
      determine the molecular weight and purity of the final product. RESULTS: A
      protein purified from pig spleen (the pig ISPS homologue) inhibited concanavalin
      A (Con A)-induced mouse lymphocyte proliferation. The molecular weight of this
      protein was about Mr 190 000. It has a stronger selectivity against T-lymphocyte
      line such as Jurkat cell line and mastocyte line (P8l5) and has a weaker
      inhibitory activity on macrophage line (U937). CONCLUSION: A protein similar to
      rat/mouse ISPS was found in pig spleen. This may provide an opportunity to study
      its roles in tumors and autoimmune diseases.

PMID- 12791189
TI  - Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus
      in ovariectomized rats.
AB  - AIM: To study the effects of low doses of hydrochloride tetracycline (Tc) on bone
      metabolism and uterus in the ovariectomized (Ova) rats. METHODS: Forty 3-month
      old rats were randomly divided into 5 groups: sham group, Ova group, Tc1 group
      (1.2 mg/kg/d), Tc2 group (4.8 mg/kg/d), and estrone group (1.48 mg/kg/d), oral
      fed for 3 months. The proximal tibia metaphyses were processed undecalcified for
      quantitative bone histomorphometry and the soft tissues were processed in
      paraffin for pathological observation. RESULTS: Placebo-treated (lactose) Ova
      rats were characterized by trabecular area (TA) decreasing and their architecture
      worsening compared with sham controls, and bone resorption was over formation
      with high bone turnover. The uteri were atrophy. (2) In estrone-treated group, TA
      and trabecular numbers were significantly increased and the trabecular separation
      decreased vs Ova group. Estrone slowed down Ova-inducing bone high turnover. But
      the size, weight, and the endometrium of the uteri in this group were increased
      vs Ova group. (3) TA was increased in both Tc1 and Tc2 groups compared with Ova
      rats. Tc maintained bone formation indices almost at Ova level, and only
      decreased mineral apposition rate (MAR) in Tc1 group, and declined bone
      resorption perimeter. The uteri and the cell of liver and kidney almost
      maintained at Ova level; Tc2 decreased labeling perimeter and increased MAR in
      comparison with Tc1 group. The uteri were atrophy, whose size maintained at Ova
      level; yellow labeling was not found in bone with these doses of Tc, while yellow
      labeling could be seen with the doses of 30 mg/kg/d of Tc for bone marker.
      CONCLUSION: The two doses of Tc have similar effects on preventing bone loss in
      Ova rats while the bone formation and uterus are not affected. However, Tc2 does
      not have more effects on increasing bone mass, Tc2 causes less mild damages to
      the liver and kidneys.

PMID- 12791190
TI  - Neurotoxicity and toxicokinetics of norfloxacin in conscious rats.
AB  - AIM: To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in
      freely moving rats. METHODS: Rats were assigned randomly to four treatment groups
      that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9 % saline,
      respectively. Electroencephalogram (EEG) was continuously recorded with a
      computerized system in freely moving rats. Venous blood samples were collected
      for determination of the NFLX concentration by microbioassay method with
      Escherichia coli 441102 as the test strain. Toxicokinetic parameters were
      determined from serum concentration-time data with the 3p97 program. RESULTS: (1)
      The epileptiform discharges appeared in all NFLX groups with different latent
      periods, accompanied with limb twitching and clonic-tonic seizures. The relative
      total power of the EEG increased. (2) Drug serum concentration-time curves of
      different doses conformed to a two-compartmental model. The values of clearance,
      volume of distribution, and terminal half-life were dose-independent, while
      maximum serum concentrations (Cmax) and the areas under the concentration-time
      curve (AUC(0-infinity)) of NFLX increased with dosage. (3) The relative total
      powers of EEG were closely correlated with the administered dose, Cmax as well as
      AUC(0-infinity). CONCLUSION: The present study established a suitable approach to
      quantitatively determine central nervous system (CNS) stimulant effect of NFLX.
      There is a significant correlation between AUC(0-infinity) and the changes of
      relative total power, which may serve as the index for judgement and prediction
      of the CNS toxic effect induced by NFLX.

PMID- 12791191
TI  - Antisense oligodeoxynucleotide inhibits vascular endothelial growth factor
      expression in U937 foam cells.
AB  - AIM: To study the expression of vascular endothelial growth factor (VEGF) induced
      by oxidized low density liporotein (ox-LDL) and the inhibitory effects of
      antisense oligodeoxynucleotide (asODN) on the levels of VEGF protein and mRNA in
      the U937 foam cells. METHODS: U937 cells were incubated with ox-LDL 80 mg/L for
      48 h, then, the foam cells were treated with asODN (0, 5, 10, and 20 micromol/L).
      The VEGF concentration in the media was determined by ELISA. The VEGF protein
      expression level in cells was measured by immuohistochemistry; the positive ratio
      detected by a morphometrical analysis system was used as the amount of the VEGF
      expression level. The VEGF mRNA level was examined by Northern blotting. RESULTS:
      After U937 cells were incubated with ox-LDL, VEGF expression level increased
      greatly both in the cells and in the media. asODN markedly inhibited the increase
      of VEGF. After treatment with asODN 20 micromol/L, the VEGF protein concentration
      in the media decreased by 45.0%, the VEGF positive ratio detected by
      immuohistochemistry in cells decreased by 64.9%, and the VEGF mRNA level
      decreased by 47.1%. CONCLUSION: The expression of VEGF in U937 foam cells was
      strong. asODN inhibited VEGF expression significantly in U937 foam cells in
      vitro.

PMID- 12791192
TI  - Efficacy of Prostant on chronic prostatitis in 119 patients.
AB  - AIM: To evaluate the efficacy and safety of Prostant in the treatment of chronic
      prostatitis. METHODS: One hundred and nineteen cases of patients who had been
      diagnosed of chronic prostatitis were treated by Prostant. The efficacy was
      evaluated by WBC in EPS and NIH Chronic Prostatitis Symptom Index after a one
      month follow-up. RESULTS: After the one-month follow-up, the total improvement
      rate is 65.5 %, the WBC in the prostatic fluid were reduced from (21+/-20) to
      (12+/-13)/High-power field (HPF); the symptom index score changed from 12+/-4 to
      7+/-5. The pain and voiding score of the symptom index were lowered from 8+/-3 to
      5+/-3 and 3.9+/-2.7 to 2.3+/-2.3 respectively. All of above showed great
      statistic differences (P<0.05). Only 2 cases (1.7 %) reported serious diarrhea.
      CONCLUSION: The Prostant is effective and safe in the treatment of chronic
      prostatitis, especially on those cases whose symptom and inflammation in
      prostatic fluid are not too serious.

PMID- 12791193
TI  - Paroxysmal Dyskinesias in Children.
AB  - Paroxysmal dyskinesias are rare movement disorders. The onset of paroxysmal
      dyskinesias in childhood are typically idiopathic (sporadic or familial), whereas
      those in adulthood are usually secondary to an identifiable cause. Paroxysmal
      dyskinesias are classified according to precipitating factors, and these include
      paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia,
      paroxysmal exertion-induced dyskinesia, and paroxysmal hypnogenic dyskinesia. The
      pathophysiology remains unknown; however, there is increasing evidence that
      channelopathies may play a role, which explains the response to anticonvulsant
      medications in certain kindreds. Pharmacologic treatment with anticonvulsant
      medications, clonazepam, tetrabenazine, trihexyphenidyl, or levodopa is reviewed
      herewith. Paroxysmal dyskinesias go by many names, but a rational classification
      does exist. Of those that respond to medications, the majority of paroxysmal
      dyskenesias respond to anticonvulsant medications. Channelopathies have been
      implemented as a cause in paroxysmal dyskinesias.

PMID- 12791194
TI  - Dopa-responsive Dystonia in Children.
AB  - Treatment of dopa-responsive dystonia is one of the more satisfying experiences
      in clinical neurology. The response to treatment with levodopa is usually
      dramatic and complete with no long-term complications. Carbidopa/levodopa is the
      mainstay in treating dopa-responsive dystonia. There is some experience using
      anticholinergic agents, but they are more likely to cause side effects and do not
      treat the underlying biochemical abnormality. Dopa-responsive dystonia caused by
      guanosine triphosphate cyclohydrolase I deficiency typically presents with
      dystonia in the lower extremities in the first decade of life. However, the
      presenting symptoms can vary. Thus, it is this author's recommendation that any
      child with dystonia receive a trial of carbidopa/levodopa.

PMID- 12791195
TI  - Sydenham Chorea in Children.
AB  - Sydenham chorea is an important cause of acquired chorea in childhood. Although
      the symptoms of chorea frequently resolve spontaneously in a matter of months,
      abnormal movements can be debilitating when they are present. Neuropsychologic
      symptoms may antedate the motor abnormality, may be persistent, and often are of
      great concern. To date, there have been no adequate, double-blind, randomized
      studies to evaluate the symptomatic treatment of Sydenham chorea. This article
      will review proposed treatment options and dosing strategies.

PMID- 12791196
TI  - Torsion Dystonia in Children.
AB  - Medical treatment of childhood-onset dystonia can lead to substantial improvement
      of the condition, often with much more pronounced benefit than in adults. The
      authors give every patient a trial of levodopa to assess the possible diagnosis
      of dopa-responsive dystonia, followed-up with centrally acting anticholinergics
      such as trihexiphenydil. If needed, baclofen or clonazepam is added or
      substituted. In focal dystonia or segmental and generalized dystonia with
      prominent involvement of specific muscle groups, botulinum toxin injections are
      often used. Pallidal deep brain stimulation is offered to selected patients with
      medically refractory dystonia. Treatment of secondary dystonias, caused by such
      conditions as Wilson's disease, requires therapy for the underlying disorder.
      Physical therapy, splints, and occupational therapy can be useful in some
      patients. The authors do not use intrathecal baclofen unless there is evidence of
      accompanying spasticity.

PMID- 12791197
TI  - Tourette's Syndrome in Children.
AB  - This paper will provide a review of the Tourette's syndrome (TS) in children,
      focusing on treatment options, including a drug-by-drug evaluation of available
      pharmacologic agents and other treatments. Despite increasing knowledge of the
      neurophysiologic basis of the tics of TS, ideal and universally effective
      treatments do not yet exist. Affected children may present a wide variety of
      phenotypes, which are best managed in a case-by-case manner, with the well
      informed patient and family weighing the risks and benefits of interventions
      together with a knowledgeable and committed clinician. The clinician treating TS
      will encounter a wide range of tic severity, comorbidity, adherence to treatment,
      and treatment response. The clinician's most important task is to identify the
      main sources of distress and impairment, and set priorities for their management.
      Common treatment may involve education and reassurance, psychosocial and school
      interventions, and choices from an array of pharmacologic agents. Decisions
      regarding treatment ought to be made collaboratively with the clinician and
      family, after a careful discussion of symptom extent and severity, psychosocial
      impact, desired outcome, and realistic treatment expectations and side effects.
      Given the waxing and waning course of tics in TS, clinicians often monitor each
      patient for several weeks before starting a somatic treatment, based on a
      judgement that even when tics are at their best, they are severe enough to
      warrant pharmacotherapy. With children for whom the decision has been taken to
      target tics with medication, the authors recommend beginning with guanfacine or
      clonidine, especially when there are any hyperactivity symptoms. The next choice
      would be a low-dose neuroleptic. Patience and close ongoing monitoring of
      efficacy and side effects is necessary, whenever a clinical trial of medications
      is undertaken, to achieve an acceptable balance between tic control and side
      effects. Treatments should be targeted at specific symptoms and comorbidities,
      such as attention deficit hyperactivity disorder and obsessive-compulsive
      disorder. Clinicians tend to treat comorbid conditions first because they may be
      the greatest sources of difficulty. On occasion, the successful treatment of a
      comorbid condition will lead to an amelioration of tics.

PMID- 12791198
TI  - Urea Cycle Disorders.
AB  - Urea cycle disorders comprise a group of inborn errors of metabolism that
      represent unique gene-nutrient interactions whose significant morbidity arises
      from acute and chronic neurotoxicity associated with often massive
      hyperammonemia. Current paradigms of treatment are focused on controlling the
      flux of nitrogen transfer through the hepatic urea cycle by a combination of
      dietary and pharmacologic approaches. Evolving paradigms include the development
      of cell and gene therapies. Current research is focused on understanding the
      pathophysiology of ammonia-mediated toxicity and prevention of neural injury.

PMID- 12791199
TI  - Biotinidase Deficiency: New Directions and Practical Concerns.
AB  - Biotinidase deficiency is a readily treatable inherited disorder. Discovery of
      the enzyme deficiency as the cause for late-onset multiple carboxylase deficiency
      initially seemed to answer almost all of the questions about the disorder.
      However, as is the case for most inborn errors of metabolism, finding the enzyme
      that causes the disorder, cloning the gene, and determining the spectrum of
      clinical features of the disease only opens a Pandora's box. As researchers have
      found, there are still many important and interesting questions about this
      disorder that must be addressed and answered. However, when compared with other
      inherited metabolic diseases, biotinidase deficiency is still one of the most
      readily treatable. If a child must have an inborn error of metabolism, let it be
      biotinidase deficiency and let it be identified by newborn screening.

PMID- 12791200
TI  - Branched-chain Ketoacyl Dehydrogenase Deficiency: Maple Syrup Disease.
AB  - Classic maple syrup disease can be managed to allow a benign neonatal course,
      normal growth, and low hospitalization rates. The majority of affected infants
      that are prospectively managed have good neurodevelopmental outcome; however,
      acute metabolic intoxication and neurologic deterioration can develop rapidly at
      any age. Each episode is associated with a risk for cerebral edema,
      cerebrovascular compromise, and brain herniation. High plasma leucine and,
      possibly, alpha-ketoisocaproate are the principal neurotoxins in maple syrup
      disease. Plasma levels rise rapidly in association with net protein catabolism
      provoked by common infections and injuries. Transient periods of maple syrup
      disease encephalopathy appear fully reversible, leaving no clinically detectable
      neurologic sequelae. In contrast, prolonged amino acid imbalance, particularly if
      occurring during the critical period of brain development, leads to neuronal
      hypoplasia, a paucity of synapses, and undermyelination. Stagnated maturation and
      inadequate nutritional maintenance of brain structure have lifelong neurologic
      and behavioral consequences. Core elements of effective long-term therapy include
      screening and identification of asymptomatic newborns, frequent plasma amino acid
      monitoring, careful attention to branched-chain amino acid nurtriture, prevention
      of cerebral essential amino acid deficiencies, adequate provision of essential
      omega-3 class fatty acids and micronutrients deficient in commercial formulas,
      methods for home monitoring of metabolic control, and a commitment to lifelong
      therapy. Recognizing the risk for acute leucine intoxication depends on
      anticipating effects of common childhood infection and physiologic stresses on
      whole body protein turnover. Successful management of metabolic decompensation is
      based on the use of home sick-day regimens, rapid availability of branched-chain
      amino acid-free hyperalimentation solutions for hospitalized children, prevention
      of hyponatremia in patients with leucinosis, and frequent adjustments of
      intravenous therapies guided by plasma amino acid levels and indices of metabolic
      and clinical response.

PMID- 12791201
TI  - Galactosemia.
AB  - Despite the dramatic response of sick neonates with galactosemia to the
      withdrawal of galactose from the diet, over the long-term, complications,
      including learning disorders, verbal apraxia, and ataxia, often develop. It is
      clear that, although lifelong galactose restriction remains the basis of
      treatment for this disease, additional treatment methods are needed. The
      neurologist familiar with galactosemia can assist in diagnosis of neonates
      presenting with central nervous system symptoms. Familiarity with the long-term
      neurologic consequences of galactosemia can help the neurologist assist the
      family with prognostic information and to avoid unnecessary tests when
      complications occur.

PMID- 12791202
TI  - Asthma and parasites: new insights.

PMID- 12791205
TI  - Patch testing for allergic contact dermatitis in the allergist office.
AB  - The identification of allergens responsible for allergic contact dermatitis (ACD)
      is key to the management of this disease. The patch test (PT) is the only safe,
      objective, scientific, and practical method for the diagnosis of ACD. There is no
      single PT panel that will screen all the relevant allergens in a patient's
      environment. It is generally thought that 20 to 30 allergens in routine screening
      tests can identify 50% to 70% of clinically relevant ACD. However, the usefulness
      of patch testing is enhanced with the number of allergens tested. Although the PT
      might be simple to apply, it might be difficult to read, interpret, and correlate
      to the patient's symptoms. A familiarity with the patient's environment, the
      process of the industry in that environment, and the uses of various chemicals in
      the industry is needed in most cases.

PMID- 12791207
TI  - Biological warfare from a dermatologic perspective.
AB  - Biological warfare agents have been used in this century by both organized armed
      forces and terrorist organizations. Beset with many problems that limit their
      tactical value on the battlefield, such "weapons of mass destruction" have
      tremendous terror appeal. Unusual presentations or clustering of diseases
      associated with biowarfare might alert the clinician that an attack has occurred.
      The clinical presentations, current recommended treatments, and preventive
      measures of agents such as anthrax, smallpox, plague, and the viral hemorrhagic
      fevers are discussed, as well as some of the issues that have been raised as
      authorities are considering how and when to resume smallpox vaccinations.
      References focus on current Internet web sites, which will provide up-to-date
      information and advice for allergists with immunization questions or who feel
      they might have encountered a patient with one of these diseases.

PMID- 12791209
TI  - Risk factors for the development of otitis media.
AB  - Otitis media (OM) is the most frequently diagnosed disease in infants and young
      children. Large, prospective studies suggest an increase in incidence of this
      disease during the past 10 to 20 years, possibly reflecting a change in host and
      environmental risk factors for the development of OM. Good knowledge of host
      (intrinsic) and environmental (extrinsic) risk factors for the development of
      otitis media is important in identifying a child at risk for recurrent and
      persistent OM. This could result in primary and/or secondary prevention of OM and
      a decrease in complications and sequelae.

PMID- 12791208
TI  - Clinical considerations in the diagnosis of otitis media.
AB  - Acute otitis media and otitis media with effusion are commonly encountered by
      both general practitioners and specialists. The diagnosis of otitis media
      requires a focused history and accurate physical examination. Unfortunately, many
      practitioners are either unaware of the criteria needed to make the diagnosis, or
      they incorrectly perform or misinterpret the physical examination. We review the
      pertinent historical and physical examination findings needed to accurately
      diagnose otitis media. Additionally, we examine the accessory tests that might
      help make the correct diagnosis in difficult cases. Finally, we address the
      issues involved in ensuring that both current and future physicians are
      appropriately trained in the diagnosis of this common illness.

PMID- 12791206
TI  - Papular urticaria and things that bite in the night.
AB  - Whether we are hiking in the back country or playing in our backyard, we run the
      risk of exposure to offending arthropods. Papular urticaria is a very common
      hypersensitivity reaction to the bites, stings, and contact with critters such as
      mites, ticks, spiders, fleas, mosquitoes, midges, flies, and even caterpillars.
      Children seem to be at greatest risk, although adults are also vulnerable. The
      classic presentation of papular urticaria includes recurrent pruritic papules or
      vesicles and varying degrees of local edema. Severity is often related to the
      host response to the salivary or contactant proteins. Our understanding of the
      immune mechanism continues to improve; however, our approach to therapy has
      remained essentially unchanged. Although this review admittedly reaches beyond
      papular urticaria, it is with the intention of improving the reader's recognition
      of the offending arthropods, the characteristics of reactions, and the current
      therapeutic approaches.

PMID- 12791211
TI  - Viral otitis media.
AB  - Acute otitis media (AOM) and viral upper respiratory tract infections (URIs)
      represent the two most common diseases affecting the human population, and
      account for substantial patient morbidity and health care costs. Epidemiologic
      and experimental studies suggest that URIs play a causal role in the pathogenesis
      of AOM. Specifically, viruses can either invade the middle ear (ME) space and
      invoke an inflammatory response that culminates in ME effusion formation and
      consequent symptoms, or URIs might cause eustachian-tube dysfunction, resulting
      in negative ME pressures and subsequent ME effusion (hydrops ex vacuo theory).
      The events responsible for the inflammatory response of the human ME following
      viral exposure have not been well characterized. Although many prophylactic and
      therapeutic interventions have been evaluated for the treatment of AOM, the
      information on virus-specific interventions is sparse. In this article, the
      epidemiology, pathogenesis, diagnosis, and management of viral otitis media are
      reviewed.

PMID- 12791210
TI  - Prevention of otitis media caused by viral upper respiratory tract infection:
      vaccines, antivirals, and other approaches.
AB  - Otitis media (OM) imposes significant morbidity on the pediatric age group and a
      large financial burden on the general population. Because standard medical
      treatments are not highly efficacious in resolving the accompanying middle ear
      (ME) inflammation, a goal of current research is OM prevention. Past studies show
      that new episodes of OM are usually a complication of viral upper respiratory
      infection (vURI), and therefore, a rational approach to achieving that goal is to
      develop intervention strategies that target vURI-associated OM. However, past
      experiences with antibiotics show that, in the absence of well-defined treatment
      protocols that maximize expected efficacy, the adoption of prophylactic or active
      treatments for OM can have negative consequences for the patient and for the
      general population. In this review, we discuss the hypothesized mechanisms by
      which a vURI is translated into an acute OM episode and describe different
      strategies for aborting that process. Limitations to deployment of each strategy
      are outlined.

PMID- 12791214
TI  - Animal models of ocular allergy and their clinical correlations.
AB  - Ocular allergic diseases represent a wide spectrum of disorders, from the acute
      self-limited, mild form of seasonal allergic conjunctivitis to the chronic,
      severe, sight-threatening atopic keratoconjunctivitis. The least problematic
      forms are the most prevalent, and several animal models have contributed to
      elucidate their etiopathogenetic mechanisms and have served to test numerous anti
      allergic compounds. The most severe and chronic, although less prevalent, ocular
      allergic problems have not benefited from a similar advance, with the subsequent
      lack of full understanding and a limited therapeutic armamentarium. Research in
      this field is currently concentrating efforts in developing more protracted
      models of ocular allergic inflammation involving the cornea and mimicking more
      closely the human disease caused by chronic ocular allergy. Most recent
      experimental models are demonstrating that inhibiting Th2 cells and their
      secreted cytokines might be one important therapeutic target for inhibiting
      chronic allergic inflammation in the ocular surface.

PMID- 12791215
TI  - Epithelial cells in ocular allergy.
AB  - Conjunctival epithelial cells do not act only as mechanical barriers, preventing
      the entry of particles, bacteria, viruses, and noxious substances into the eye
      but they are also active participants in the regulation of allergic inflammation
      via expressing adhesion/effector molecules (intercellular adhesion molecule-1,
      vascular cell adhesion molecule-1, human leukocyte antigen-DR, CD40/CD40L,
      Fas/Fas ligand) on their surfaces and releasing numerous proinflammatory
      cytokines, such as eotaxin, regulated on activation normal T-cell expressed and
      released (RANTES), macrophage inflammatory protein-1, interleukin (IL)-8, IL-6,
      and tumor necrosis factor-a, which are necessary for the proliferation,
      differentiation, activation, and chemotaxis of various inflammatory cells into
      the conjunctiva. Histamine, released from the conjunctival mast cells, might
      stimulate the synthesis of proinflammatory molecules such as IL-6 and IL-8 by the
      epithelial cells through the receptors that couple to inositol phosphate
      generation and, therefore, amplify the allergic response. The relationship
      between the epithelium and allergy should be considered in detail in future
      studies aiming at an effective control and treatment of all forms of allergic
      conjunctivitis.

PMID- 12791216
TI  - T-cell characterization in chronic allergic eye disease.
AB  - Chronic allergic eye disease encompasses several disorders, but it is vernal
      keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) that have sight
      threatening sequelae. T cells, eosinophils, and mast cells are all found in the
      conjunctiva, and are thought to play a role in disease pathogenesis. Recently,
      the conjunctival epithelium has also been considered to play a key role. New and
      effective therapeutic strategies for the future for these patients depend on
      achieving a greater understanding of the roles and interactions of the cell
      populations in these sight-threatening disorders.

PMID- 12791218
TI  - Oral vitamin D3 decreases fracture risk in the elderly.
AB  - Vitamin D3 (or its physiologic equivalent, ergocalciferol), administered at a
      dose of 100,000 IU every 4 months for 5 years, is effective for primary
      prevention of fractures in the active elderly aged 65 to 85 years. This treatment
      regimen has no effect on cardiovascular, cancer, or all-cause mortality. Despite
      a seemingly large dose averaging 800 IU per day, this regimen is a safe, cheap
      (<$2 per year), and effective therapy for primary prevention of fractures.

PMID- 12791217
TI  - Conjunctival allergen challenge: models in the investigation of ocular allergy.
AB  - Recently, the number of agents to treat ocular allergy has increased
      dramatically, from three (pheniramine, antazoline, cromolyn) to more than a
      dozen. A general increase in the incidence of atopy in recent years and the fact
      that patients are becoming less tolerant of bothersome signs and symptoms have
      been driving forces in this increase. As visual tasking, such as reading and
      working on a computer, has become more prevalent, there is an increased awareness
      of ocular allergy and the impact it has on quality of life and productivity at
      work and school. With the need for more effective medications, the development of
      models, such as the conjunctival allergen challenge (CAC), has made the
      identification of new agents more efficient. In this article, we review the
      relevant background on the science behind allergen challenges in the eye, how
      models are designed, and how models are used in the field today.

PMID- 12791219
TI  - Analgesics do not interfere with diagnosing abdominal pain.
AB  - Despite the limitations in this review, it seems appropriate to administer
      analgesics to patients with generalized abdominal pain, even before a surgical
      evaluation. Surgeons can be assured that they will not be misled as a result of
      analgesia.

PMID- 12791220
TI  - ACE inhibitors are better than diuretics for treatment of hypertension in the
      elderly.
AB  - Despite similar reductions in blood pressure, angiotensin-converting enzyme (ACE)
      inhibitors demonstrate lower combined rates of cardiovascular events or all-cause
      mortality in elderly hypertensive patients compared with diuretics. This benefit
      is most evident in men. These results may differ from those of the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT)
      trial because that study included younger patients, had a greater representation
      of patients with African ancestry, used different brands of medication, and had a
      slightly different primary outcome. Despite these differences, both treatments
      offer an inexpensive means for reducing blood pressure and preventing
      hypertension-related complications.

PMID- 12791221
TI  - Not all fish products prevent heart disease.
AB  - For patients aged >65 years, modest consumption of tuna and other broiled/baked
      fish is associated with a lower risk of death from ischemic heart disease and
      fatal arrhythmias. The same is not true of fried fish or fish burgers. Instruct
      patients that not all fish products provide the same health effects.

PMID- 12791222
TI  - Cognitive behavioral therapy and exercise minimally help Gulf War veterans'
      illnesses.
AB  - Cognitive behavioral therapy and aerobic exercise provide only modest relief from
      symptoms of Gulf War veterans' illnesses. Unfortunately, over 80% of the patients
      showed no improvement of symptoms after 1 year of either or both treatments. With
      the Iraqi war ending, the outcomes of veterans of this previous conflict may
      prove significant.

PMID- 12791223
TI  - Admission electronic fetal monitoring does not improve neonatal outcomes.
AB  - Admission electronic fetal monitoring did not decrease neonatal morbidity and
      mortality compared with intermittent auscultation. Patients in the admission
      fetal monitoring group were more likely to receive continuous electronic
      monitoring and fetal blood sampling, but there were no significant differences in
      the rates of operative deliveries or episiotomy. Institutions not routinely using
      admission electronic fetal monitoring should not start; those that do may not be
      benefiting their patients.

PMID- 12791224
TI  - Is terazosin helpful in chronic prostatitis?
AB  - Terazosin, an alpha-1-adrenergic blocker, is well tolerated, relieves pain
      symptoms, and improves quality of life in healthy men aged 20 to 50 years who
      have chronic prostatitis/chronic pelvic pain syndrome. Terazosin should be
      strongly considered as a first-line treatment in such patients. However, men with
      infectious prostatitis were excluded from this study. Also, the benefits of
      terazosin beyond 14 weeks are unknown.

PMID- 12791225
TI  - Topical ophthalmic NSAIDs reduce pain faster than placebo.
AB  - Topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) relieve the pain
      of uncomplicated acute corneal abrasions faster than placebo eyedrops. The pain
      relief is small; whether the pain relief difference would be noticed by patients
      and how it compares with oral analgesics is unknown. Given the cost of topical
      NSAIDs, they are most useful for a select patient population: those who must
      return to work immediately, and those for whom opioid analgesia-induced sedation
      is intolerable.

PMID- 12791226
TI  - Patients with mild scoliosis have good prognosis.
AB  - Patients with late-onset idiopathic scoliosis have only a modest increase in
      health problems compared with patients without scoliosis. Clinicians should keep
      this in mind when providing health education and offer reassurance and watchful
      waiting to patients with small curves at skeletal maturity. More broadly, whether
      to screen for scoliosis depends on the performance of the screening test as well
      as evidence of whether treatment alters the natural history of scoliosis. The US
      Preventive Services Task Force has concluded that there is insufficient evidence
      to recommend routine screening.

PMID- 12791227
TI  - 12-hour protocol safe for cocaine-associated chest pain.
AB  - A 12-hour emergency department observation period is safe for patients with
      cocaine-associated chest pain, provided they have symptoms consistent with low-to
      intermediate likelihood of unstable angina according to the Braunwald
      classification, and normal serial troponin I levels and cardiogram. Patients with
      traditional cardiac risk factors should undergo cardiac stress testing within 2
      weeks following the chest pain event, as atherosclerosis enhances the
      vasoconstrictive effects of cocaine. All patients should be referred for
      substance abuse counseling, as recurrent cocaine use was associated with
      subsequent nonfatal myocardial infarction.

PMID- 12791228
TI  - Treatment of skin malignancies.
AB  - Malignant melanomas in situ can usually be treated in consultation with a
      specialist (C). Larger lesions may require referral. Based on best available
      evidence, surgical excision is the first-line treatment for most nonmelanoma skin
      cancers, with cure rates as high as 98% with proper margins. Consider Mohs
      surgery for larger lesions, sclerosing lesions with morpheaform histology, or for
      cosmetically sensitive areas. With properly selected lesions,
      curettage/electrodesiccation and cryosurgery have cure rates comparable to that
      of surgical excision.

PMID- 12791230
TI  - Variations in color.

PMID- 12791229
TI  - Herbs for serum cholesterol reduction: a systematic view.
AB  - OBJECTIVES: To systematically review the clinical evidence for herbal medicinal
      products in the treatment of hypercholesterolemia. STUDY DESIGN: A systematic
      review of randomized clinical trials of herbal medicinal products used to lower
      serum cholesterol. Systematic literature searches were conducted in 6 electronic
      data-bases. The reference lists of all papers and our files were searched for
      more relevant publications. Experts in the field and manufacturers of identified
      herbal medicinal products were contacted for published and unpublished data. No
      language restrictions were imposed. OUTCOMES MEASURED: All randomized clinical
      trials of serum cholesterol reduction, in which mono-preparations of herbal
      medicinal products were administered as supplements to human subjects, were
      included. RESULTS: Twenty-five randomized clinical trials involving 11 herbal
      medicinal products were identified. Guggul (Commiphora mukul), fenugreek
      (Trigonella foenum-graecum), red yeast rice, and artichoke (Cynara scolymus) have
      been most extensively studied and have demonstrated reductions in total serum
      cholesterol levels of between10% and 33%. The methodological quality as assessed
      by the Jadad score was less than 3 (maximum, 5) for 13 of the 25 trials.
      CONCLUSIONS: Many herbal medicinal products have potential hypocholesterolemic
      activity and encouraging safety profiles. However, only a limited amount of
      clinical research exists to support their efficacy. Further research is warranted
      to establish the value of these extracts in the treatment of
      hypercholesterolemia.

PMID- 12791231
TI  - Clinical inquiries. Does daily monitoring of blood glucose predict hemoglobin A1c
      levels?

PMID- 12791232
TI  - Clinical inquiries. Are antibiotics helpful for acute maxillary sinusitis?

PMID- 12791233
TI  - Clinical inquiries. What is the most effective nicotine replacement therapy?

PMID- 12791234
TI  - Clinical inquiries. What is the prognosis of postherpetic neuralgia?

PMID- 12791235
TI  - Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory
      syndrome virus and associations with the production of apoptogenic cytokines.
AB  - Apoptosis was studied in the lungs of pigs during an infection with a European
      strain of porcine reproductive and respiratory syndrome virus (PRRSV) and it was
      examined if cytokines were involved in the induction of apoptosis. Twenty-two 4-
      to 5-week-old gnotobiotic pigs were inoculated intranasally with 10(6.0) TCID50
      of the Lelystad virus and euthanised between 1 and 52 days post inoculation (PI).
      The lungs and broncho-alveolar lavage (BAL) cells were assessed both for virus
      replication and apoptosis; BAL fluids were examined for interleukin (IL)-1,
      tumour necrosis factor-alpha and IL-10. Double-labellings were conducted to
      determine the relation between virus replication and apoptosis and to identify
      the apoptotic cells. Apoptosis occurred in both infected and non-infected cells.
      The percentages of infected cells, which were apoptotic, ranged between 9 and 39%
      in the lungs and between 13 and 30% in the BAL cells. The majority of apoptotic
      cells were non-infected. Non-infected apoptotic cells in the lungs were
      predominantly monocytes/macrophages, whereas those in the broncho-alveolar spaces
      were predominantly lymphocytes. The peak of apoptosis in the lungs at 14 days PI
      was preceded by a peak of IL-1 and IL-10 production at 9 days PI, suggesting a
      possible role of these cytokines in the induction of apoptosis in non-infected
      interstitial monocytes/macrophages. However, the latter hypothesis was not
      confirmed in vitro, since blood monocytes or alveolar macrophages did not undergo
      apoptosis after treatment with recombinant porcine IL-1 or IL-10.

PMID- 12791236
TI  - Temporal and spatial patterns of the clinical surveillance of BSE in France,
      analysed from January 1991 to May 2002 through a vigilance index.
AB  - Between 1991 and mid 2000, the surveillance of Bovine Spongiform Encephalopathy
      (BSE) in France was based solely on clinical surveillance through a Mandatory
      Reporting System. Since 2000, the implementation of active surveillance
      programmes using rapid tests, as a complementary tool targeted at dead and
      slaughtered cattle has shown that part of the BSE cases were not detected with
      the clinical surveillance. In order to obtain a better knowledge of the strength
      of the clinical surveillance, we analysed a vigilance index defined as the ratio
      of negative clinical suspicions to the cattle population in the region and period
      of interest. The temporal analysis of the vigilance index showed that it did not
      vary much between 1991 and 1999, increased sharply since 2000, and then decreased
      partly in 2001. The geographical analysis of the variations of the vigilance
      index was performed at the department level by comparing the observed number of
      negative clinical suspicions per department to the expected number, computed on
      the basis of the national average index and standardised on the production type
      of the cattle - dairy versus beef suckling cattle. As assumed, the data followed
      a Poisson distribution. We observed a high geographical variation of the
      vigilance index: ten departments out of 91 presented a significantly higher
      vigilance index than the national one, and four a significantly lower vigilance
      index. The vigilance index showed that the clinical surveillance was
      heterogeneous during the past twelve years, both in time and geographic location,
      in a range of one to ten. So the apparent trend in the BSE epidemic during this
      period as well as the differences in the spatial incidence of BSE have to be
      analysed with caution.

PMID- 12791237
TI  - In vitro infection of aortic endothelial cells by caprine arthritis encephalitis
      virus enhances in vitro transmigration of peripheral blood leukocytes and
      modulates their phenotypic expression.
AB  - Infection of goats by caprine arthritis-encephalitis virus (CAEV) provides a
      convenient example of the infiltration of various tissues by leukocytes following
      a natural lentiviral infection. This event is important in determining organ
      susceptibility and local immunity. Caprine vascular endothelial cells are
      susceptible to infection by CAEV in vitro, so we have investigated the
      consequences of this infection on the transmigration of uninfected leukocytes in
      an in vitro model. After in vitro infection by CAEV or stimulation by TNFalpha,
      the endothelial cells allowed the passage of tenfold more leukocytes from
      uninfected donors than did the uninfected endothelial cells. The transmigrating
      leukocytes were enriched in CD8+ lymphocytes, and the leukocytes appeared to have
      been activated during transmigration, as demonstrated by their expression of
      IL2R, MHC class II antigens and gamma-delta T-lymphocyte markers. CD4+, CD8+ and
      B-lymphocytes all proliferated in culture after transmigration. These results
      suggest that any possible infection or specific stimulation of endothelia in an
      infected animal could profoundly influence the choice of target organs and could
      activate the cells involved in local mucosal immune responses.

PMID- 12791238
TI  - Enteropathogenicity of Dutch and German avian reoviruses in SPF white leghorn
      chickens and broilers.
AB  - The enteropathogenicity of avian reoviruses (ARVs), isolated from chickens
      affected with malabsorption syndrome (MAS) from The Netherlands and Germany was
      studied. In the first trial seven different ARVs isolated from MAS cases were
      inoculated in 1-day-old specific pathogenic free (SPF) white leghorns. The
      pathogenicity was compared with 2 ARVs isolated from cases of tenosynovitis,
      namely reference strain S1133 and a Dutch strain. Although a difference in the
      severity of the clinical disease was observed, all reoviruses could induce
      vacuolar degeneration and sloughing of the epithelium of the small intestine at
      day 2 post inoculation (PI) till day 7 PI. Two Dutch and one German ARV derived
      from MAS causing the most severe intestinal lesions at day 2 PI, were further
      studied in the second trial using SPF broilers. These reoviruses did not cause
      weight gain depression in the broilers although lesions in the small intestine
      were present from day 1 up to day 4 PI and were more severe than in the white
      leghorn chickens. In one of the inoculated groups apical denuded villi were
      already present at day 1 PI. At day 7 PI the small intestine of the infected
      broilers appeared to be normal. Reovirus antigen was detected in the cytoplasm of
      the enterocytes at the tip and middle section of the affected villi both in
      layers and in broilers. To study the role of intestinal CD4+ and CD8+ T-cells and
      macrophages/monocytes in the pathogenesis of ARV, the numbers of these cells of
      the jejunal villi of one infected and the control broiler groups were compared.
      CD4+ T-cells were detected in low numbers and only in the infected broiler group
      at day 14 PI. The numbers of CD8+ T-cells and macrophages/monocytes were
      significantly higher in the infected broiler group than in the control broiler
      group at day 7 and 14 PI and at day 7 PI respectively. Our study indicates that
      the reovirus alone cannot induce intestinal lesions as found in MAS chickens.
      Moreover, CD8+ T-cells may play a major role in the pathogenesis and or reovirus
      clearance in the small intestine.

PMID- 12791239
TI  - Evaluation of a modified Rose Bengal test and an indirect enzyme-linked
      immunosorbent assay for the diagnosis of Brucella melitensis infection in sheep.
AB  - A modified Rose Bengal test (mRB) and an indirect ELISA (iELISA) with Protein G
      as the conjugate, were evaluated for the diagnosis of Brucella melitensis
      infection in unvaccinated sheep with a known bacteriological status, and their
      diagnostic efficacy was compared with that of the standard Rose Bengal (RB) and
      Complement Fixation (CF) tests used in the current eradication campaign in EU
      countries. All tests showed 100% specificity when testing the sera from 212
      Brucella-free sheep. When testing the sera from 219 Brucella melitensis culture
      positive sheep, both the mRB and iELISA tests were more sensitive (98.6% and
      96.8%, respectively) than the RB and CF tests (95.0% and 92.7%, respectively).
      These results were similar when testing the sera from 181 animals belonging to
      infected flocks but found bacteriologically negative, suggesting that the mRB or
      iELISA tests could advantageously replace the current RB procedure used as the
      screening test.

PMID- 12791240
TI  - Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli
      mastitis in mice.
AB  - Endotoxin, or lipopolysaccharide (LPS), is responsible for pathogenesis of
      infections induced by Gram-negative bacteria, such as E. coli. The cellular
      response to LPS is modulated by interactions among LPS, LPS-binding protein (LBP)
      and CD14. Accumulated evidence shows that the soluble form of CD14 (sCD14)
      competes with membrane-bound CD14 (mCD14) for LPS and plays a pivotal role in
      regulating bacterial infection and septic shock caused by Gram-negative bacteria.
      Recombinant bovine sCD14 (rbosCD14) was produced by transfected insect sf/9 cells
      and its biological function was evaluated in mice. Eighty-one 8-week old BALB/cj
      female mice were randomly assigned to two groups, and injected intraperitoneally
      with either LPS (8 microg/g of body weight, n = 41) or LPS plus rbosCD14 (6.8
      microg/g of body weight, n = 40). Survival rate at 24 h after injection for mice
      injected with either LPS or LPS plus rbosCD14 was 30 and 72%, respectively (P <
      0.01). At 48 h survival rate was 7 and 37%, respectively (P < 0.01). To
      investigate the protective effect of rbosCD14 on experimentally induced mastitis
      in mice, two abdominal contralateral mammary glands of 7 lactating BALB/cj mice
      were injected through the teat canal with 10-20 colony-forming units (CFU) of
      Escherichia coli. One gland simultaneously received rbosCD14 (6 microg) and the
      other saline. At 24 h after challenge, glands that received rbosCD14 had less
      swelling and hemorrhaging, significantly lower bacterial counts (P < 0.05) and
      lower concentrations of TNF-alpha (P < 0.05). Results indicate that rbosCD14 is
      biologically functional and reduces mortality in mice from endotoxin shock and
      severity of intramammary infection by E. coli.

PMID- 12791241
TI  - Equine trypsin: purification and development of a radio-immunoassay.
AB  - Shock is accompanied by generalised splanchnic hypoperfusion, and splanchnic
      organs like the pancreas can be damaged, as shown in animal experimental models
      and in humans, by the presence of high plasma concentrations of trypsin and other
      pancreatic enzymes. In order to design a radioimmunoassay technique (RIA) for the
      measurement of equine trypsin-like immunoreactivity (TLI) in biological fluids,
      trypsin was purified (with purity > or = 96%) from the equine pancreas by
      extraction in an acid medium, ammonium sulfate precipitations, gel filtration
      chromatography and, after activation of trypsinogen into trypsin, affinity
      chromatography. Gel polyacrylamide electrophoresis showed a monomeric enzyme with
      a molecular weight of 27 kDa. The purified equine trypsin served for the
      immunisation of rabbits in order to obtain a specific antiserum, and the labelled
      antigen was prepared by iodination of equine trypsin with 125I. The RIA was based
      on the binding of the antigen to the antibody followed by the separation of the
      antigen-antibody complex by immunoprecipitation in the presence of sheep anti
      rabbit gammaglobulins and the assay of the radioactivity in the precipitate. The
      RIA showed good sensitivity, specificity, precision, accuracy and
      reproducibility. The reference mean value of TLI in the plasma of healthy horses
      (n = 20) was 30.01+/-6.84 ng/mL (upper confidence limit 50.52 ng/mL; p < 0.01).
      Three horses with non strangulating intestinal obstruction without shock showed
      TLI values within normal limits whereas 5 of 7 horses with strangulation
      obstruction showed TLI levels above the upper confidence limit. Further studies
      using the RIA and the enzymatic assay should be performed in order to confirm the
      role of the pancreas in equine intestinal obstruction.

PMID- 12791243
TI  - Influence of age and purpose for testing on the cut-off selection of serological
      methods in bovine neosporosis.
AB  - The aim of this study was to investigate the need for different cut-off points,
      according to animal age and the purpose of testing, for two of the most widely
      used serological techniques in bovine neosporosis, IFAT and a crude antigen ELISA
      (Civtest, HIPRA). Therefore, the population reference sera used were defined
      using a combination of multiple criteria such as epidemiological/clinical and
      histopathological parameters and an immunoblot test. Firstly, foetuses and
      breeding cattle (heifers and cows) were considered as separate subpopulations for
      serological evaluation. Secondly, cut-off points for each serological technique
      (IFAT and ELISA) according to age group (foetuses and breeding cattle) and the
      different practical applications (detection of infection and abortion) were
      calculated following the receiver operating characteristics (ROC) analysis. Cut
      off points were defined, for IFAT and ELISA for aborted breeding cattle and for
      IFAT alone in the case of the foetuses, assuming an equivalent cost of false
      positive and negative results. In infected breeding cattle, for IFAT and ELISA
      and in foetuses for ELISA, two possible cut-off values were obtained, one for a
      maximum sensitivity and one for a maximum specificity and the intervals of
      unclear results were defined. In this case, a cut-off value for equal sensitivity
      and specificity was also estimated. When cut-off points for infected breeding
      cattle, 1:100-1:250 for IFAT and 0.306-0.451 for ELISA were applied to a target
      population, optimal and similar negative and positive predictive values together
      with similar apparent and true prevalence results were observed suggesting the
      possibility of using both tests interchangeably.

PMID- 12791242
TI  - Effects of condensed tannins on established populations and on incoming larvae of
      Trichostrongylus colubriformis and Teladorsagia circumcincta in goats.
AB  - The use of tanniferous plants or tannins represents one alternative approach to
      the control of gastrointestinal parasites in ruminants but most data have been
      obtained in sheep. The current study was therefore performed in goats with two
      objectives: firstly, to investigate the effects of condensed tannins (CT) on
      adult populations of Trichostrongylus colubriformis and Teladorsagia
      circumcincta; secondly, to examine their effects on the establishment of
      infective larvae of these two species. In experiment 1, two groups of kids were
      infected with 6 000 L3 of T. colubriformis and 6 000 L3 of T. circumcincta. After
      7 weeks, quebracho extracts were administered per os for 8 days to one group. A
      comparable group which did not receive tannins was included as the control. The
      kids were slaughtered on week 11. Parasitological and pathophysiological
      parameters were measured weekly. Worm counts were assessed and mast cells,
      globule leukocytes and eosinophils were counted in the abomasal and intestinal
      mucosae. Tannin administration was associated with a decrease in egg excretion,
      and a decrease in female fecundity, but with no changes in worm numbers. These
      changes were associated with an increased number of intestinal mast cells. In
      experiment 2, 24 goats were used according to a 2 x 2 factorial design, depending
      on infection and tannin administration. Two groups were either infected with 6
      000 L3 of T. colubriformis or T. circumcincta. Within each group, the goats were
      either drenched or undrenched with tannin extracts. Pathophysiological parameters
      were measured weekly. Twelve days after the cessation of tannin administration,
      the goats were slaughtered. Worm counts and female worm fecundity were
      determined. Tannin consumption was associated with a significant reduction (P <
      0.01) of Trichostrongylus populations and a close to significant reduction for
      Teladorsagia. No effect on fecundity was observed. Our results (1) confirm the
      consequences of condensed tannins on nematodes in goats as in sheep and (2)
      indicate divergent effects depending on the parasitic stage exposed to the
      condensed tannins.

PMID- 12791244
TI  - Phylogenetic relationship of equine Actinobacillus species and distribution of
      RTX toxin genes among clusters.
AB  - Equine Actinobacillus species were analysed phylogenetically by 16S rRNA gene
      (rrs) sequencing focusing on the species Actinobacillus equuli, which has
      recently been subdivided into the non-haemolytic A. equuli subsp. equuli and the
      haemolytic A. equuli subsp. haemolyticus. In parallel we determined the profile
      for RTX toxin genes of the sample of strains by PCR testing for the presence of
      the A. equuli haemolysin gene aqx, and the toxin genes apxI, apxII, apxIII and
      apxIV, which are known in porcine pathogens such as Actinobacillus
      pleuropneumoniae and Actinobacillus suis. The rrs-based phylogenetic analysis
      revealed two distinct subclusters containing both A. equuli subsp. equuli and A.
      equuli subsp. haemolyticus distributed through both subclusters with no
      correlation to taxonomic classification. Within one of the rrs-based subclusters
      containing the A. equuli subsp. equuli type strain, clustered as well the porcine
      Actinobacillus suis strains. This latter is known to be also phenotypically
      closely related to A. equuli. The toxin gene analysis revealed that all A. equuli
      subsp. haemolyticus strains from both rrs subclusters specifically contained the
      aqx gene while the A. suis strains harboured the genes apxI and apxII. The aqx
      gene was found to be specific for A. equuli subsp. haemolyticus, since A. equuli
      subsp. equuli contained no aqx nor any of the other RTX genes tested. The
      specificity of aqx for the haemolytic equine A. equuli and ApxI and ApxII for the
      porcine A. suis indicates a role of these RTX toxins in host species predilection
      of the two closely related species of bacterial pathogens and allows PCR based
      diagnostic differentiation of the two.

PMID- 12791245
TI  - CPV, a stable and symmetrical machine for mRNA synthesis.
AB  - The structure of cytoplasmic polyhedrosis virus (CPV), an insect pathogen from
      the Reoviridae family of double-strand RNA viruses, has been determined at 8 A by
      electron cryomicroscopy and image reconstruction. It provides new information
      about the functions of these viral particles as stable machines for mRNA
      synthesis.

PMID- 12791246
TI  - Complementing thymidylate synthase.
AB  - The structure of thymidylate synthase complementing protein with substrates dUMP
      and FAD, presented in this issue of Structure, sheds light on a fascinating new
      catalytic mechanism, suggests a strategy for the design of new antimicrobial
      compounds, and highlights the promise of proteomics in medicine.

PMID- 12791247
TI  - A pivotal role of the coiled coil of Sir4.
AB  - The C terminus of Sir4 forms a coiled-coil structure. The coiled-coil domain is
      responsible for the dimerization of Sir4 and contains the binding site of Sir3.
      Structural and biochemical analyses of the Sir4 coiled-coil domain provide
      important insights into the molecular mechanisms of Sir3-Sir4 interaction and the
      assembly of a ternary Sir2/Sir3/Sir4 complex that are essential for epigenetic
      control of gene expression in S. cerevisiae.

PMID- 12791248
TI  - How carbohydrate binding modules overcome ligand complexity.
AB  - The first crystal structure of a carbohydrate binding module in complex with a
      substituted oligosaccharide has provided important insights into how these
      proteins are able to target the backbone of complex polysaccharides that are
      extensively decorated.

PMID- 12791249
TI  - Activating MAP KAP kinase 2.
AB  - The crystal structures of MAP KAP kinase 2 in complex with ADP and staurosporine
      suggest a major reorganization of the glycine-rich loop upon ligand binding. The
      main determinant for the catalytic activity of MAP KAP kinase 2 is
      phosphorylation by p38 MAP kinase.

PMID- 12791251
TI  - Structural and functional analysis of the actin binding domain of plectin
      suggests alternative mechanisms for binding to F-actin and integrin beta4.
AB  - Plectin is a widely expressed cytoskeletal linker. Here we report the crystal
      structure of the actin binding domain of plectin and show that this region is
      sufficient for interaction with F-actin or the cytoplasmic region of integrin
      alpha6beta4. The structure is formed by two calponin homology domains arranged in
      a closed conformation. We show that binding to F-actin induces a conformational
      change in plectin that is inhibited by an engineered interdomain disulfide
      bridge. A two-step induced fit mechanism involving binding and subsequent domain
      rearrangement is proposed. In contrast, interaction with integrin alpha6beta4
      occurs in a closed conformation. Competitive binding of plectin to F-actin and
      integrin alpha6beta4 may rely on the observed alternative binding mechanisms and
      involve both allosteric and steric factors.

PMID- 12791250
TI  - A growing family of natural killers.
AB  - The structure of the natural cytotoxicity receptor NKp44, described in this issue
      of Structure, adds to our rapidly expanding knowledge of the structure of natural
      killer cell receptors, which play a key role in the elimination of virally
      infected and tumor cells during innate immune responses.

PMID- 12791252
TI  - Catalytically active MAP KAP kinase 2 structures in complex with staurosporine
      and ADP reveal differences with the autoinhibited enzyme.
AB  - MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the
      inflammatory process. We have determined the crystal structures of a
      catalytically active C-terminal deletion form of human MK2, residues 41-364, in
      complex with staurosporine at 2.7 A and with ADP at 3.2 A, revealing overall
      structural similarity with other Ser/Thr kinases. Kinetic analysis reveals that
      the K(m) for ATP is very similar for MK2 41-364 and p38-activated MK2 41-400.
      Conversely, the catalytic rate and binding for peptide substrate are dramatically
      reduced in MK2 41-364. However, phosphorylation of MK2 41-364 by p38 restores the
      V(max) and K(m) for peptide substrate to values comparable to those seen in p38
      activated MK2 41-400, suggesting a mechanism for regulation of enzyme activity.

PMID- 12791253
TI  - Structure of the coiled-coil dimerization motif of Sir4 and its interaction with
      Sir3.
AB  - The yeast silent information regulators Sir2, Sir3, and Sir4 physically interact
      with one another to establish a transcriptionally silent state by forming
      repressive chromatin structures. The Sir4 protein contains binding sites for both
      Sir2 and Sir3, and these protein-protein interactions are required for gene
      silencing. Here, we report the X-ray structure of the coiled-coil dimerization
      motif within the C-terminus of Sir4 and show that it forms a stable 1:1 complex
      with a dimeric fragment of Sir3 (residues 464-978). We have identified a cluster
      of residues on the surface of the Sir4 coiled coil required for specific
      interactions with Sir3. The histone deacetylase Sir2 can also bind to this
      complex, forming a ternary complex with the truncated Sir3 and Sir4 proteins. The
      dual interactions of Sir4 with Sir3 and Sir2 suggest a physical basis for
      recruiting Sir3 to chromatin by virtue of its interactions with Sir4 and with
      deacetylated histones in chromatin.

PMID- 12791254
TI  - Cytoplasmic polyhedrosis virus structure at 8 A by electron cryomicroscopy:
      structural basis of capsid stability and mRNA processing regulation.
AB  - The single-shelled cytoplasmic polyhedrosis virus (CPV) is a unique member of the
      Reoviridae. Despite lacking protective outer shells, it exhibits striking capsid
      stability and is capable of endogenous RNA transcription and processing. The 8 A
      three-dimensional structure of CPV by electron cryomicroscopy reveals secondary
      structure elements present in the capsid proteins CSP, LPP, and TP, which have
      alpha+beta folds. The extensive nonequivalent interactions between CSP and LPP,
      the unique CSP protrusion domain, and the perfect inter-CSP surface
      complementarities may account for the enhanced capsid stability. The slanted
      disposition of TP functional domains and the stacking of channel constrictions
      suggest an iris diaphragm-like mechanism for opening/closing capsid pores and
      turret channels in regulating the highly coordinated steps of mRNA transcription,
      processing, and release.

PMID- 12791255
TI  - Structural and thermodynamic dissection of specific mannan recognition by a
      carbohydrate binding module, TmCBM27.
AB  - The C-terminal 176 amino acids of a Thermotoga maritima mannanase (Man5)
      constitute a carbohydrate binding module (CBM) that has been classified into CBM
      family 27. The isolated CBM27 domain, named TmCBM27, binds tightly (K(a)s 10(5)
      10(6) M(-1)) to beta-1, 4-mannooligosaccharides, carob galactomannan, and konjac
      glucomannan, but not to cellulose (insoluble and soluble) or soluble birchwood
      xylan. The X-ray crystal structures of native TmCBM27, a TmCBM27-mannohexaose
      complex, and a TmCBM27-6(3),6(4)-alpha-D-galactosyl-mannopentaose complex at 2.0
      A, 1.6 A, and 1.35 A, respectively, reveal the basis of TmCBM27's specificity for
      mannans. In particular, the latter complex, which is the first structure of a CBM
      in complex with a branched plant cell wall polysaccharide, illustrates how the
      architecture of the binding site can influence the recognition of naturally
      substituted polysaccharides.

PMID- 12791256
TI  - Functional analysis of substrate and cofactor complex structures of a thymidylate
      synthase-complementing protein.
AB  - Like thymidylate synthase (TS) in eukaryotes, the thymidylate synthase
      complementing proteins (TSCPs) are mandatory for cell survival of many
      prokaryotes in the absence of external sources of thymidylate. Details of the
      mechanism of this novel family of enzymes are unknown. Here, we report the
      structural and functional analysis of a TSCP from Thermotoga maritima and its
      complexes with substrate, analogs, and cofactor. The structures presented here
      provide a basis for rationalizing the TSCP catalysis and reveal the possibility
      of the design of an inhibitor. We have identified a new helix-loop-strand FAD
      binding motif characteristic of the enzymes in the TSCP family. The presence of a
      hydrophobic core with residues conserved among the TSCP family suggests a common
      overall fold.

PMID- 12791257
TI  - Structural basis for a direct interaction between FGFR1 and NCAM and evidence for
      a regulatory role of ATP.
AB  - The neural cell adhesion molecule (NCAM) promotes axonal outgrowth, presumably
      through an interaction with the fibroblast growth factor receptor (FGFR). NCAM
      also has a little-understood ATPase activity. We here demonstrate for the first
      time a direct interaction between NCAM (fibronectin type III [F3] modules 1 and
      2) and FGFR1 (Ig modules 2 and 3) by surface plasmon resonance (SPR) analysis.
      The structure of the NCAM F3 module 2 was determined by NMR and the module was
      shown by NMR to interact with the FGFR1 Ig module 3 and ATP. The NCAM sites
      binding to FGFR and ATP were found to overlap and ATP was shown by SPR to inhibit
      the NCAM-FGFR binding, indicating that ATP probably regulates the NCAM-FGFR
      interaction. Furthermore, we demonstrate that the NCAM module was able to induce
      activation (phosphorylation) of FGFR and to stimulate neurite outgrowth. In
      contrast, ATP inhibited neurite outgrowth induced by the module.

PMID- 12791258
TI  - The crystal structure of choline kinase reveals a eukaryotic protein kinase fold.
AB  - Choline kinase catalyzes the ATP-dependent phosphorylation of choline, the first
      committed step in the CDP-choline pathway for the biosynthesis of
      phosphatidylcholine. The 2.0 A crystal structure of a choline kinase from C.
      elegans (CKA-2) reveals that the enzyme is a homodimeric protein with each
      monomer organized into a two-domain fold. The structure is remarkably similar to
      those of protein kinases and aminoglycoside phosphotransferases, despite no
      significant similarity in amino acid sequence. Comparisons to the structures of
      other kinases suggest that ATP binds to CKA-2 in a pocket formed by highly
      conserved and catalytically important residues. In addition, a choline binding
      site is proposed to be near the ATP binding pocket and formed by several
      structurally flexible loops.

PMID- 12791259
TI  - High-resolution structures of RmlC from Streptococcus suis in complex with
      substrate analogs locate the active site of this class of enzyme.
AB  - Nature achieves the epimerization of carbohydrates by a variety of chemical
      routes. One common route is that performed by the class of enzyme defined by dTDP
      6-deoxy-D-xylo-4-hexulose 3,5-epimerase (RmlC) from the rhamnose pathway. Earlier
      studies failed to identify the key residues in catalysis. We report the 1.3 A
      structure of RmlC from Streptococcus suis type 2 and its complexes with dTDP-D
      glucose and dTDP-D-xylose. The streptococcal RmlC enzymes belong to a separate
      subgroup, sharing only 25% identity with RmlC from other bacteria, yet the S.
      suis enzyme has similar kinetic properties and structure to other RmlC enzymes.
      Structure, sequence alignment, and mutational analysis have now allowed reliable
      identification of the catalytic residues and their roles.

PMID- 12791260
TI  - The three-dimensional structure of the human NK cell receptor NKp44, a triggering
      partner in natural cytotoxicity.
AB  - Natural killer (NK) cells direct cytotoxicity against tumor or virally infected
      cells. NK cell activation depends on a fine balance between inhibitory and
      activating receptors. NKp44 is a cytotoxicity activating receptor composed of one
      Ig-like extracellular domain, a transmembrane segment, and a cytoplasmic domain.
      The 2.2 A crystal structure shows that the NKp44 Ig domain forms a saddle-shaped
      dimer, where a charged surface groove protrudes from the core structure in each
      subunit. NKp44 Ig domain disulfide bridge topology defines a new Ig structural
      subfamily. The data presented are a first step toward understanding the molecular
      basis for ligand recognition by natural cytotoxicity receptors, whose key role in
      the immune system is established, but whose cellular ligands are still elusive.

PMID- 12791261
TI  - A mitochondrial rhomboid protease.
AB  - Rhomboid proteases are integral membrane proteins, typically associated with
      cleavage of peptide hormones along the secretory pathway. Recent publications
      demonstrate that yeast mitochondria contain a rhomboid protease required for the
      cleavage of two mitochondrial intermembrane space proteins, suggesting that
      rhomboid proteases play a regulatory role in mitochondria.

PMID- 12791262
TI  - Finally, worm polycomb-like genes meet Hox regulation.
AB  - Polycomb and Trithorax group proteins have been shown to regulate Hox gene
      expression in flies and mammals, but not in worms. Two reports in this issue of
      Developmental Cell establish a first link between Polycomb-like genes and Hox
      gene regulation in C. elegans. However, sequence comparison indicates that these
      genes may not be homologous to the fly Polycomb genes, suggesting that
      independent gene recruitment occurred during nematode evolution.

PMID- 12791263
TI  - Regulation by phosphorylation. Yet another twist in the WASP story.
AB  - Cell migration and other complex cellular processes involve a variety of
      signaling molecules and require the integration of multiple signals into a
      coherent cytoskeletal response. Two papers in the May issue of Molecular Cell now
      demonstrate that phosphorylation plays a critical role in WASP function as a
      regulator of Arp2/3-mediated actin polymerization.

PMID- 12791264
TI  - Peering through the pore: nuclear pore complex structure, assembly, and function.
AB  - Nuclear pore complexes (NPCs) are large proteinaceous assemblies that provide the
      only known portals for exchanging macromolecules between the nucleus and
      cytoplasm. This includes the movement of small molecules and the selective,
      facilitated transport of large proteins and RNAs. Faithful, continuous NPC
      assembly is key for maintaining normal physiological function and is closely tied
      to proper cell division. This review focuses on the most outstanding issues
      involving NPC structure, assembly, and function.

PMID- 12791265
TI  - A Wnt-Wnt situation.
AB  - A recent Juan March Foundation workshop on "wnt genes and Wnt signaling" brought
      developmental and cancer biologists together to share some of the latest advances
      in Wnt research. Discussion topics included molecular, genetic, and genomic
      dissections of wnt genes in embryogenesis and cancer, Wnt signaling components
      and downstream targets, interactions with other signaling pathways, cell
      biological aspects of Wnt signaling, and a first glimpse of a purified Wnt
      protein.

PMID- 12791266
TI  - Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in
      vivo.
AB  - SCF ubiquitin ligases, composed of three major subunits, Skp1, Cul1, and one of
      many F box proteins (Fbps), control the proteolysis of important cellular
      regulators. We have inactivated the gene encoding the Fbp beta-Trcp1 in mice.
      beta-Trcp1(-/-) males show reduced fertility correlating with an accumulation of
      methaphase I spermatocytes. beta-Trcp1(-/-) MEFs display a lengthened mitosis,
      centrosome overduplication, multipolar metaphase spindles, and misaligned
      chromosomes. Furthermore, cyclin A, cyclin B, and Emi1, an inhibitor of the
      anaphase promoting complex, are stabilized in mitotic beta-Trcp1(-/-) MEFs.
      Indeed, we demonstrate that Emi1 is a bona fide substrate of beta-Trcp1. In
      contrast, stabilization of beta-catenin and IkappaBalpha, two previously reported
      beta-Trcp1 substrates, does not occur in the absence of beta-Trcp1 and instead
      requires the additional silencing of beta-Trcp2 by siRNA. Thus, beta-Trcp1
      regulates the timely order of meiotic and mitotic events.

PMID- 12791268
TI  - The protooncogene c-myc is an essential regulator of neural crest formation in
      xenopus.
AB  - The neural crest, a population of multipotent progenitor cells, is a defining
      feature of vertebrate embryos. Neural crest precursor cells arise at the neural
      plate border in response to inductive signals, but much remains to be learned
      about the molecular mechanisms underlying their induction. Here we show that the
      protooncogene c-Myc is an essential early regulator of neural crest cell
      formation in Xenopus. c-myc is localized at the neural plate border prior to the
      expression of early neural crest markers, such as slug. A morpholino-mediated
      "knockdown" of c-Myc protein results in the absence of neural crest precursor
      cells and a resultant loss of neural crest derivatives. These effects are not
      dependent upon changes in cell proliferation or cell death. Instead, our findings
      reveal an important and unexpected role for c-Myc in the specification of cell
      fates in the early ectoderm.

PMID- 12791267
TI  - Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase
      activates the anaphase promoting complex to allow progression beyond
      prometaphase.
AB  - Progression through mitosis occurs because cyclin B/Cdc2 activation induces the
      anaphase promoting complex (APC) to cause cyclin B destruction and mitotic exit.
      To ensure that cyclin B/Cdc2 does not prematurely activate the APC in early
      mitosis, there must be a mechanism delaying APC activation. Emi1 is a protein
      capable of inhibiting the APC in S and G2. We show here that Emi1 is
      phosphorylated by Cdc2, and on a DSGxxS consensus site, is subsequently
      recognized by the SCF(betaTrCP/Slimb) ubiquitin ligase and destroyed, thus
      providing a delay for APC activation. Failure of betaTrCP-dependent Emi1
      destruction stabilizes APC substrates and results in mitotic catastrophe
      including centrosome overduplication, potentially explaining mitotic deficiencies
      in Drosophila Slimb/betaTrCP mutants. We hypothesize that Emi1 destruction
      relieves a late prophase checkpoint for APC activation.

PMID- 12791269
TI  - Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell
      differentiation.
AB  - Dramatic changes in morphology and myelin protein expression take place during
      the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating
      oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the
      differentiation process. Molecules that could induce Fyn signaling have not been
      studied. Such molecules are promising therapeutic targets in demyelinating
      diseases. We provide evidence that the common gamma chain of immunoglobulin Fc
      receptors (FcRgamma) is expressed in OPCs and has a role in triggering Fyn
      signaling. FcRgamma cross-linking by immunoglobulin G on OPCs promotes the
      activation of Fyn signaling and induces rapid morphological differentiation with
      upregulation of myelin basic protein (MBP) expression levels. Mice deficient in
      FcRgamma are hypomyelinated, and a significant reduction in MBP content is
      evident. Our findings indicate that the FcRgamma-Fyn-MBP cascade is pivotal
      during the differentiation of OPCs into myelinating oligodendrocytes, revealing
      an unexpected involvement of immunological molecules.

PMID- 12791270
TI  - Distinction between color photoreceptor cell fates is controlled by Prospero in
      Drosophila.
AB  - The Drosophila compound eye consists of approximately 750 independently
      functioning ommatidia, each containing two photoreceptor subpopulations. The
      outer photoreceptors participate in motion detection, while the inner
      photoreceptors contribute to color vision. Although the inner photoreceptors, R7
      and R8, terminally differentiate into functionally related cells, they differ in
      their molecular and morphological makeup. Our data indicates that several aspects
      of R7 versus R8 cell fate determination are regulated by the transcription factor
      Prospero (Pros). pros is specifically expressed in R7 cells, and R7 cells mutant
      for pros derepress R8 rhodopsins, lose R7 rhodopsins and acquire an R8-like
      morphology. This suggests that R7 inner photoreceptor cell fate is acquired from
      a default R8-like fate that is regulated, in part, via the direct transcriptional
      repression of R8 rhodopsins in R7 cells. Furthermore, this study provides
      transcriptional targets for pros that may lend insight into its role in
      regulating neuronal development in flies and vertebrates.

PMID- 12791271
TI  - c-Jun is essential for organization of the epidermal leading edge.
AB  - The migration of epithelial layers requires specific and coordinated organization
      of the cells at the leading edge of the sheet. Mice that are conditionally
      deleted for the c-jun protooncogene in epidermis are born at expected
      frequencies, but with open eyes and with defects in epidermal wound healing.
      Keratinocytes lacking c-Jun are unable to migrate or elongate properly in culture
      at the border of scratch assays. Histological analyses in vitro and in vivo
      demonstrate an inability to activate EGF receptor at the leading edge of wounds,
      and we demonstrate that this can be rescued by supplementation with conditioned
      medium or the EGF receptor ligand HB-EGF. Lack of c-Jun prevents EGF-induced
      expression of HB-EGF, indicating that c-jun controls formation of the epidermal
      leading edge through its control of an EGF receptor autocrine loop.

PMID- 12791272
TI  - c-Jun regulates eyelid closure and skin tumor development through EGFR signaling.
AB  - To investigate the function of c-Jun during skin development and skin tumor
      formation, we conditionally inactivated c-jun in the epidermis. Mice lacking c
      jun in keratinocytes (c-jun(Deltaep)) develop normal skin but express reduced
      levels of EGFR in the eyelids, leading to open eyes at birth, as observed in EGFR
      null mice. Primary keratinocytes from c-jun(Deltaep) mice proliferate poorly,
      show increased differentiation, and form prominent cortical actin bundles, most
      likely because of decreased expression of EGFR and its ligand HB-EGF. In the
      absence of c-Jun, tumor-prone K5-SOS-F transgenic mice develop smaller
      papillomas, with reduced expression of EGFR in basal keratinocytes. Thus, using
      three experimental systems, we show that EGFR and HB-EGF are regulated by c-Jun,
      which controls eyelid development, keratinocyte proliferation, and skin tumor
      formation.

PMID- 12791273
TI  - Polycomb group regulation of Hox gene expression in C. elegans.
AB  - Polycomb group (PcG) chromatin proteins regulate homeotic genes in both animals
      and plants. In Drosophila and vertebrates, PcG proteins form complexes and
      maintain early patterns of Hox gene repression, ensuring fidelity of
      developmental patterning. PcG proteins in C. elegans form a complex and mediate
      transcriptional silencing in the germline, but no role for the C. elegans PcG
      homologs in somatic Hox gene regulation has been demonstrated. Surprisingly, we
      find that the PcG homologs MES-2 [E(Z)] and MES-6 (ESC), along with MES-3, a
      protein without known homologs, do repress Hox expression in C. elegans. mes
      mutations cause anteroposterior transformations and disrupt Hox-dependent
      neuroblast migration. Thus, as in Drosophila, vertebrates, and plants, C. elegans
      PcG proteins regulate key developmental patterning genes to establish positional
      identity.

PMID- 12791274
TI  - Global regulation of Hox gene expression in C. elegans by a SAM domain protein.
AB  - Polycomb group (PcG)-mediated repression of C. elegans Hox genes has not been
      demonstrated, and genes homologous to components of one of the PcG complexes
      (PRC1) have not been identified in the C. elegans genome. We find that a
      mechanism of general Hox gene repression exists in C. elegans, carried out in
      part by SOP-2, a protein related to, but not orthologous with, any PcG protein.
      sop-2 mutations lead to widespread ectopic expression of Hox genes and homeotic
      transformations. SOP-2 contains a SAM domain, a self-associating protein domain
      found in other repressors, including a core component of PRC1 and ETS
      transcription factors. Phylogenetic analysis indicates that this domain is more
      closely related to those of the ETS family than to those of PcG proteins. The
      results suggest that global repression of Hox genes has been taken over by a
      different branch of the SAM domain family during the evolution of nematodes.

PMID- 12791275
TI  - A hedgehog-responsive region in the Drosophila wing disc is defined by debra
      mediated ubiquitination and lysosomal degradation of Ci.
AB  - Transcription factor Ci mediates Hedgehog (Hh) signaling to determine the
      anterior/posterior (A/P) compartment of Drosophila wing disc. While Hh-inducible
      genes are expressed in A compartment cells abutting the A/P border, it is unclear
      how the boundaries of this region are established. Here, we have identified a Ci
      binding protein, Debra, that is expressed at relatively high levels in the band
      abutting the border of the Hh-responsive A compartment region. Debra mediates the
      polyubiquitination of full-length Ci, which then leads to its lysosomal
      degradation. Debra is localized in the multivesicular body, suggesting that the
      polyubiquitination of Ci directs its sorting into lysosome. Thus, Debra defines
      the border of the Hh-responsive region in the A compartment by inducing the
      lysosomal degradation of Ci.

PMID- 12791276
TI  - Auxilin-dynamin interactions link the uncoating ATPase chaperone machinery with
      vesicle formation.
AB  - The large GTPase dynamin is required for budding of clathrin-coated vesicles from
      the plasma membrane, after which the clathrin coat is removed by the chaperone
      Hsc70 and its cochaperone auxilin. Recent evidence suggests that the GTP-bound
      form of dynamin may recruit factors that execute the fission reaction. Here, we
      show that dynamin:GTP binds to Hsc70 and auxilin. We mapped two domains within
      auxilin that interact with dynamin, and these domains inhibit endocytosis when
      overexpressed in HeLa cells or when added in a permeable cell assay. The
      inhibition is not due to impairment of clathrin uncoating or to altered clathrin
      distribution in cells. Thus, in addition to its requirement for clathrin
      uncoating, our results show that auxilin also acts during the early steps of
      clathrin-coated vesicle formation. The data suggest that dynamin regulates the
      action of molecular chaperones in vesicle budding during endocytosis.

PMID- 12791277
TI  - Asymmetric distribution of nuclear pore complexes and the cytoplasmic
      localization of beta2-tubulin mRNA in Chlamydomonas reinhardtii.
AB  - Although it is generally accepted that nuclear architecture is an important
      determinant of nuclear activity, it is not clear whether cytoplasmic events, such
      as transcript localization and cell polarity, are affected by this architecture.
      Characterization of the nuclear architecture of the single-cell alga
      Chlamydomonas reinhardtii revealed a polarized nucleus, with nuclear pore
      complexes preferentially concentrated at the posterior side of the nucleus.
      Nuclear asymmetry was greatly exaggerated during the upregulation of genes
      encoding flagellar proteins, when nuclear pore complexes (NPCs) were observed to
      hyperpolarize to the posterior side of the nucleus while heterochromatin
      polarized to the anterior side. Interestingly, prior to deflagellation, the beta2
      tubulin gene was preferentially located in the posterior region of the nucleus,
      and following deflagellation, beta2-tubulin transcripts accumulated posteriorly
      in polysome-rich cytoplasmic regions adjacent to the highest concentration of
      NPCs, suggesting a connection between nuclear architecture and cytoplasmic
      transcript localization.

PMID- 12791279
TI  - Chemoenzymatic synthesis of the sialyl-alpha-(2-->3')-lactosamine trisaccharide
      with a 3-aminopropyl group as a spacer at the reducing end.
AB  - The trisaccharide, 3-aminopropyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D
      galacto-2-nonulopyranosylonic acid-(2-->3)-beta-D-galactopyranosyl-(1-->4)-2
      acetamido-2-deoxy-beta-D-glucopyranoside has been synthesized chemoenzymatically
      for the first time. First, the acceptor, 3-aminopropyl beta-D-galactopyranosyl-(1
      ->4)-2-acetamido-2-deoxy-beta-D-glucopyranoside was synthesized in a conventional
      chemical manner, and then it was coupled with CMP-sialic acid using alpha-(2-->3)
      (N)-sialyltransferase to afford the desired trisaccharide by an enzymatically
      stereocontrolled manner.

PMID- 12791280
TI  - New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous
      antithrombotics.
AB  - In the search for new orally active antithrombotic drugs that are metabolically
      stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives,
      examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl,
      alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C
      linked analogues of 5-thio-D-xylopyranosides.

PMID- 12791282
TI  - Structural features of a pectic arabinogalactan with immunological activity from
      the leaves of Diospyros kaki.
AB  - A water-soluble acidic heteroglycan, DL-3Bb, isolated from the leaves of
      Diospyros kaki, had [alpha](D)(20) -19.9 degrees (c 0.30, water), and contained
      rhamnose, arabinose, xylose, galactose and galacturonic acid in the molar ratio
      of 1.0:4.5:0.7:1.5:1.0. About 44% of the galacturonic acid existed as its methyl
      ester, and O-acetyl groups (approx 5.7%) were also identified. Its molecular
      weight was determined to be 9.0x10(5) Da by high-performance gel-permeation
      chromatography. Its structural features were elucidated by a combination of
      methylation analysis, periodate oxidation, two steps of partial acid hydrolysis,
      and 1H and 13C NMR spectroscopy and ESI mass spectrometry. The data obtained
      indicated that DL-3Bb possessed a backbone of a disaccharide of [-->4)-alpha
      GalAp-(1-->2)-alpha-Rhap-(1-->], with approx 58.7% substitution at O-4 of the
      rhamnopyranosyl residues by beta-(1-->4)-linked xylopyranosyl residues, and by
      beta-(1-->3) and beta-(1-->6)-linked galactopyranosyl (galactan) residues. The
      side chains were further substituted by arabinofuranosyl residues at O-2 by beta
      (1-->4)-linked xylopyranosyl residues and at O-3 by beta-(1-->6)-linked
      galactopyranosyl residues. Preliminary tests in vitro revealed that it could
      stimulate LPS-induced B lymphocyte proliferation, but not for ConA-induced T
      lymphocyte proliferation. It was proposed that the acid-labile arabinofuranosyl
      residues in the side chains would not be needed for the expression of the
      enhancement of the immunological activity, and that the presence of GalAp in the
      backbone has an important, but not crucial effect on the expression of the
      activity.

PMID- 12791281
TI  - Low molecular weight chitosans--preparation by depolymerization with Aspergillus
      niger pectinase, and characterization.
AB  - The viscosity of a chitosan solution was rapidly lowered in the presence of
      pectinase from Aspergillus niger at pH 3.0 and 37 degrees C. The low molecular
      weight chitosans (LMWC) had a molecular weight in the range 20,000-5000 Da.
      Circular dichroism spectra showed a decrease in the segment of acetylated
      glucosamine units, whereas X-ray diffraction and CP-MAS 13C NMR indicated higher
      crystallinity and polymorphism in LMWC. The latter on thermal drying resulted in
      structural alterations, and yielded an insoluble product. FT-IR and X-ray
      diffraction showed no evidence of either Schiff's base linkage or any annealed
      polymorph. CP-MAS 13C NMR showed marked changes in the chain conformations of
      LMWC, which are believed to be responsible for its loss of solubility and
      functionality.

PMID- 12791284
TI  - Chemical composition of carrageenan blends determined by IR spectroscopy combined
      with a PLS multivariate calibration method.
AB  - The content of kappa, iota and lambda carrageenan in mixtures was determined by
      application of FT-IR spectroscopy combined with partial least-squares
      multivariate regression (PLS). This method allows the determination of the
      relative amounts of the different carrageenans in a rapid and accurate manner.

PMID- 12791283
TI  - Synthesis and conformational analysis of the repeating units of bacterial spore
      peptidoglycan.
AB  - Deprotection of the fully blocked disacharide allyl O-(2-amino-4,6-O-benzylidene
      3-O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranosyl-1',2-lactam)-(1-->4)-2
      acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside by selective de-O
      allylation and parallel removal of the benzylidene and O-benzyl groups is
      described. The resulting beta-muramyl lactam-(1-->4)-GlcNAc disaccharide is
      characterised as the per-O-acetylated derivative by 1H and 13C NMR spectroscopy
      and X-ray structure analysis. Conformational analysis about glycosidic bond of
      repeating units of bacterial spore cortex is based on experimental data and
      molecular modelling.

PMID- 12791285
TI  - Synthesis of biantennary beta-D-(1-->6) glucosamine oligosaccharides.
AB  - Biantennary beta-D-(1-->6) glucosamine hexa-, octa-, and dodecaoligosaccharide
      derivatives were synthesized convergently using isopropyl thioglycosides as
      donors in NIS/TMSOTf-catalyzed glycosylation.

PMID- 12791286
TI  - Preparation of 2,6-anhydro-aldose acylhydrazones, -semicarbazones and -oximes
      from 2,6-anhydro-aldononitriles (glycosyl cyanides).
AB  - Reductive transformation of per-O-acylated 2,6-anhydro-aldononitriles
      (glycopyranosyl cyanides of the D-galacto, D-gluco, D-xylo, and D-arabino
      configuration) with Raney-nickel-NaH(2)PO(2) in pyridine-AcOH-water solvent
      mixture in the presence of benzoylhydrazine, ethyl carbazate, and semicarbazide
      gave the corresponding anhydro-aldose benzoylhydrazones, 
      ethoxycarbonylhydrazones, and -semicarbazones, respectively. Acid catalyzed
      transimination of the semicarbazones with thiosemicarbazide, hydroxylamine, and O
      benzylhydroxylamine, resulted in the formation of anhydro-aldose
      thiosemicarbazones, and E/Z mixtures of anhydro-aldose oximes, and O-benzyl
      (anhydro-aldose)-oximes, respectively.

PMID- 12791287
TI  - An efficient and selective method for preparing glycosyl sulfoxides by oxidizing
      glycosyl sulfides with OXONE or t-BuOOH on SiO2.
AB  - Silica gel adsorbed with OXONE or t-BuOOH was used as a mild oxidant to
      selectively oxidize glycosyl sulfides to corresponding sulfoxides in good yields
      and without sulfones formation. This method was also found compatible with
      various other functional groups in the glycosides.

PMID- 12791288
TI  - Cloning expression and characterization of a thermostable exopolygalacturonase
      from Thermotoga maritima.
AB  - A gene encoding for a thermostable exopolygalacturonase (exo-PG) from
      hyperthermophilic Thermotoga maritima has been cloned into a T7 expression vector
      and expressed in Escherichia coli. The gene encoded a polypeptide of 454 residues
      with a molecular mass of 51,304 Da. The recombinant enzyme was purified to
      homogeneity by heat treatment and nickel affinity chromatography. The
      thermostable enzyme had maximum of hydrolytic activity for polygalacturonate at
      95 degrees C, pH 6.0 and retains 90% of activity after heating at 90 degrees C
      for 5 h. Study of the catalytic activity of the exopolygalacturonase,
      investigated by means of 1H NMR spectroscopy revealed an inversion of
      configuration during hydrolysis of alpha-(1-->4)-galacturonic linkage.

PMID- 12791290
TI  - Golgi disassembly in apoptosis: cause or effect?
AB  - The Golgi complex undergoes a dramatic disassembly process during apoptosis. Some
      Golgi proteins implicated in Golgi structure and vesicle transport are cleaved
      during apoptosis, and expression of noncleavable mutants of these proteins delays
      Golgi disassembly after pro-apoptotic stimuli. Cleavage of Golgi structural
      proteins and subsequent disassembly of the organelle could simply be the result
      of the apoptotic process. However, recent studies raise the intriguing
      possibility that cleavage of Golgi proteins during apoptosis might be required
      for more than disassembly of the organelle.

PMID- 12791289
TI  - Mechanistic study of the intramolecular conversion of maltose to trehalose by
      Thermus caldophilus GK24 trehalose synthase.
AB  - This paper questions what types of molecular transformation are involved in the
      conversion of maltose to trehalose by trehalose synthase from Thermus caldophilus
      GK24. The reverse reaction pathway has been examined with the aid of alpha,alpha
      (2,4,6,6',2',4',6",6"'-(2)H(8))trehalose (1). The mass data of the isolated
      reaction products clearly indicate that deuterated glucose is confined only to
      substrate molecules, and thus the reversible enzymatic conversion of trehalose
      into maltose proceeds through an intramolecular pathway.

PMID- 12791291
TI  - Polar transport of auxin: carrier-mediated flux across the plasma membrane or
      neurotransmitter-like secretion?
AB  - Auxin (indole-3-acetic acid) has its name derived from the Greek word auxein,
      meaning 'to increase', and it drives plant growth and development. Auxin is a
      small molecule derived from the amino acid tryptophan and has both hormone- and
      morphogen-like properties. Although there is much still to be learned, recent
      progress has started to unveil how auxin is transported from cell-to-cell in a
      polar manner. Two recent breakthrough papers from Gerd Jurgens' group indicate
      that auxin transport is mediated by regulated vesicle trafficking, thus
      encompassing neurotransmitter-like features.

PMID- 12791292
TI  - No evidence for PHD fingers as ubiquitin ligases.

PMID- 12791294
TI  - Evolving views of telomerase and cancer.
AB  - The maintenance of telomeres, nucleoprotein structures that constitute the ends
      of eukaryotic chromosomes, regulates many crucial cellular functions and might,
      in multicellular organisms, participate in the control of complex phenotypes such
      as aging and cancer. Stabilization of telomere length is strongly associated with
      cellular immortalization, and constitutive telomerase activation occurs in most
      human cancers. Such observations form the basis for the prevailing model that
      postulates that alterations in telomere biology both suppress and facilitate
      malignant transformation by regulating genomic stability and cell life span.
      However, recent findings suggest that telomere maintenance might not be an
      obligate requirement for initial tumor formation in some settings and that
      telomerase activation contributes to tumorigenesis independently of its role in
      maintaining telomere length. These recent developments indicate that our
      understanding of telomere biology remains incomplete and implicate additional
      complexity in the relationships among telomeres, telomerase and cancer.

PMID- 12791295
TI  - Signals for COPII-dependent export from the ER: what's the ticket out?
AB  - Export of many secretory proteins from the endoplasmic reticulum (ER) relies on
      signal-mediated sorting into ER-derived transport vesicles. Recent work on the
      coat protein complex II (COPII) provides new insight into the mechanisms and
      signals that govern this selective export process. Conserved di-acidic and di
      hydrophobic motifs found in specific transmembrane cargo proteins are required
      for their selection into COPII-coated vesicles. These signaling elements are
      cytoplasmically exposed and recognized by subunits of the COPII coat. Certain
      soluble cargo molecules depend on receptor-like proteins for efficient ER export,
      although signals that direct soluble cargo into ER-derived vesicles are less
      defined.

PMID- 12791296
TI  - Drosophila tracheal morphogenesis: intricate cellular solutions to basic plumbing
      problems.
AB  - The cellular architecture of tubular organs suggests striking similarities in the
      mechanisms of tubulogenesis between species. The formation of the Drosophila
      respiratory organ (trachea) highlights the basic principles of branch patterning
      and tube growth that generate a highly elaborate but stereotyped epithelial
      tubular network. Oriented cell migration, changes in cell shape, selective growth
      of the apical cell membrane and intracellular lumen formation are essential
      events in this process. These morphogenetic processes build four structurally
      distinct classes of tubes that facilitate optimal airflow and gas exchange with
      target tissues. The molecular players in these plots include attractant and
      repellent signals, differentiation factors that cause a high diversity of cell
      fates within the epithelium, and determinants of tube formation and dimensions.

PMID- 12791297
TI  - Epithelial cell adhesion and the regulation of gene expression.
AB  - Epithelial cells adhere to their neighbors and the extracellular matrix by means
      of adhesion complexes composed of transmembrane components connected to
      cytoplasmic proteins and the cytoskeleton. Recent results suggest that these
      complexes not only mediate adhesion but are also engaged in the transmission of
      signals from the plasma membrane to the nucleus to regulate gene expression. Main
      mediators of such signal-transduction processes are proteins that localize to
      sites of adhesion and the nucleus. Here, we review such signal-transduction
      pathways and discuss how they influence cell proliferation and differentiation.

PMID- 12791298
TI  - The interplay of nuclear mRNP assembly, mRNA surveillance and export.
AB  - Fully processed mRNAs are exported to the cytoplasm where they direct protein
      synthesis. Export of mRNAs is mediated by a conserved heterodimeric transport
      receptor (known as NXF1-p15 in metazoa) that binds to mRNA cargoes either
      directly or indirectly by means of adaptor proteins. Upon binding, the receptor
      translocates the cargo across the central channel of the nuclear pore complex
      (NPC) by interacting directly with NPC proteins called nucleoporins. Our
      understanding of the molecular mechanisms by which the heterodimeric receptor is
      recruited to cellular mRNAs indicates that the adaptors, together with additional
      proteins, are loaded cotranscriptionally to nascent mRNAs to form large
      ribonucleoprotein complexes (mRNPs). This mRNP assembly process might be subject
      to quality control by a nuclear mRNP surveillance mechanism, so that aberrantly
      assembled mRNPs are degraded before the receptor delivers them to the cytoplasm.

PMID- 12791299
TI  - How to make tubes: signaling by the Met receptor tyrosine kinase.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF), acting through the receptor
      tyrosine kinase Met, stimulates cells derived from a variety of different organs
      to form elongated hollow tubules when grown in three-dimensional gels. In vivo
      data also indicate a role for HGF/SF and Met in tubule formation during liver and
      kidney regeneration and mammary gland formation. Activation of Met results in the
      recruitment of a myriad of signal transducers that regulate dissociation of
      adherens junctions and the stimulation of cellular motility, survival,
      proliferation and morphogenesis during tubule formation. Among these many signal
      transducers, the Gab1 adaptor protein and its effector, the SHP2 tyrosine
      phosphatase, have been found to be crucial for tubulogenesis and for the
      sustained stimulation of the ERK/MAP kinase pathway. Here, we discuss the
      contribution of these and other signaling pathways and the role of HGF/SF and Met
      in the formation of epithelial cell tubules both in vitro in branching
      morphogenesis assays and in vivo during organogenesis.

PMID- 12791300
TI  - Nickel induces oxidative stress and genotoxicity in human lymphocytes.
AB  - In order to elucidate the oxidative effects and genotoxicity of nickel on human
      lymphocytes in vitro, we report the level of intracellular reactive oxygen
      species (ROS), lipid peroxidation, hydroxyl radical ((*)OH), and DNA damage in
      human lymphocytes after acute exposure to inorganic nickel. NiCl(2) appeared to
      increase the formation of the fluorescent oxidized compound dichlorofluorescein
      (DCF). Lipid peroxidation in lymphocytes significantly increased compared to
      control. 2,3- and 2,5-DHB increased markedly in a concentration-dependent manner.
      Single-strand DNA breakage induced by Ni in lymphocytes was evaluated by Comet
      assay. Significant increase in DNA damage score (arbitrary units) showed a dose
      related elevation after treatment with NiCl(2). NiCl(2) induced lipid
      peroxidation at 0.5 mM but had no effect on DNA strand breakage. These results
      support the emerging concept that NiCl(2)-induced oxidative stress and
      genotoxicity may be caused by oxygen radical intermediates. NiCl(2)-induced DNA
      strand breakage is related to the generation of the (*)OH radical.

PMID- 12791301
TI  - Assessment of biotransformation of the arene moiety of styrene in volunteers and
      occupationally exposed workers.
AB  - Styrene is a chemical widely used in the plastic industry. The main pathway of
      styrene metabolism in humans occurs via the oxidation to styrene-7,8-oxide (7,8
      SO). The aim of this study was the investigation of a minor metabolic route,
      involving the oxidation of the arene moiety of styrene, by means of the
      characterization of the conjugated urinary metabolites of 4-vinylphenol (4-VP). 4
      vinylphenol-glucuronide (4-VP-G) and -sulfate (4-VP-S), were measured by liquid
      chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) from 174
      workers belonging to three cohorts recruited in European countries and from 26
      volunteers exposed to 50 mg/m(3) (11.8 ppm) of styrene for 8 h. The 4-VP
      conjugates represented about 0.5-1% of the total excretion of styrene
      metabolites. Both 4-VP-G and 4-VP-S are eliminated with a monophasic kinetic, the
      glucuronide being excreted faster (half-time, 2.2 +/- 0.2 h) than the sulfate
      (half-time 9.7 +/- 1.7 h). The urinary 4-VP was found to be significantly
      correlated both with airborne styrene (r = 0.607, p < 0.001) and the sum of MA
      and PGA (r = 0.903, p < 0.001 in "end-of-shift" samples). Apart from 7,8-SO, 4-VP
      is the only styrene metabolite not shared with ethylbenzene and therefore thought
      to be a highly specific marker of styrene exposure. However, a measurable
      background excretion of 4-VP was also found in all urine samples from controls
      not occupationally exposed to styrene. This background appears to be highly
      correlated to smoking (p < 0.001) and possibly also to the dietary intake of
      styrene or 4-VP. Consequently, the use of 4-VP as a biomarker of styrene exposure
      is recommended for exposures exceeding 1 ppm.

PMID- 12791302
TI  - Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air:
      lowest observable effect level.
AB  - Realistic scenarios for low-level exposure to nerve agents will often involve
      exposures over several hours to extremely low doses of agent. In order to expose
      animals to the lowest controllable concentrations of agent and to increase
      exposure times until a lowest observable effect level (LOEL) becomes measurable,
      a validated system was developed for exposing conscious animals to 0.05-1.0
      microg/m(3) (8-160 ppt) of sarin and other nerve agents. Based on cold trapping
      of sarin from the exposure air, the concentration could be measured
      semicontinuously, at 4-min time intervals by means of gas chromatography. We
      found that the LOEL upon a 5-h whole body exposure of guinea pigs and marmosets
      to sarin vapor corresponds with the measurement of an internal dose by means of
      fluoride-induced regeneration of sarin from phosphylated binding sites in plasma,
      mostly BuChE. For guinea pigs the LOEL was observed at Ct = 0.010 +/- 0.002
      mg/min/m(3), whereas a Ct of 0.04 +/- 0.01 mg/min/m(3) was established for the
      LOEL in marmosets. These levels are several orders of magnitude lower than those
      based on classical measurement of depressed cholinesterase activities. At low
      exposure levels of guinea pigs and marmosets (< or =1 microg/m(3)), a reasonable
      linearity was observed between exposure dose and internal dose. The data were
      addressed in the light of the recently recommended occupational exposure limits
      to sarin for workers without respiratory protection, which suggests that the
      exposure limits should be reconsidered if the slightest inhibition of
      cholinesterases should be prevented.

PMID- 12791303
TI  - Cadmium alters the localization of N-cadherin, E-cadherin, and beta-catenin in
      the proximal tubule epithelium.
AB  - Recent studies on proximal tubule-derived cells in culture have shown that Cd has
      relatively specific damaging effects on the cadherin-dependent junctions between
      the cells. The objective of the present study was to determine whether Cd can
      affect cadherin-dependent junctions in the proximal tubule epithelium in vivo.
      Male Sprague-Dawley rats received subcutaneous injections of Cd (0.6 mg/kg in
      isotonic saline, 5 days per week for up to 6 weeks). One day each week, 24-h
      urine samples were collected and analyzed for protein and creatinine. After 5-6
      weeks, the Cd-treated animals developed significant proteinuria, with no change
      in creatinine excretion. Visualization of pan-cadherin immunoreactive materials
      by immunoperoxidase labeling showed that Cd caused a marked reduction in the
      intensity of cadherin labeling associated with the apical and the basolateral
      surfaces of the epithelial cells of the proximal tubule, but no change in the
      pattern of cadherin labeling in other segments of the nephron. Results of studies
      utilizing specific antibodies against N-cadherin, E-cadherin, and beta-catenin
      showed changes in the localization of all three molecules in the proximal tubule.
      Assessment of cell membrane integrity with trypan blue and ethidium homodimer
      showed no overt evidence of death in the proximal tubule epithelial cells.
      Additional results showed that Cd caused only a slight increase in the total
      levels of glutathione and no significant peroxidation of membrane lipids,
      indicating only a modest level of oxidative stress. These results indicate that
      Cd can disrupt cadherin-dependent cell-cell junctions in the proximal tubule, and
      they raise the possibility that a loss of cadherin-mediated adhesion may
      contribute to the nephrotoxic effects of Cd.

PMID- 12791304
TI  - Sex differences in L-type calcium current after chronic ethanol consumption in
      rats.
AB  - Chronic ethanol consumption elicits a progressive cardiac contractile
      dysfunction, and studies in rats suggest that this alcoholic heart muscle disease
      is more pronounced in males than females. Cellular changes associated with the
      ethanol-induced cardiotoxicity remain largely undefined; however, it is possible
      that L-type Ca(2+) channel current (I(Ca,L)) is affected. Using whole-cell patch
      clamp techniques, this study examined I(Ca,L) in adult ventricular myocytes
      isolated from male and female P-rats that had consumed drinking water (controls)
      or a 25% ethanol/water mixture for 14 months. The peak amplitude and maximum
      conductance of I(Ca,L) were 32 and 26% greater, respectively, in cardiomyocytes
      isolated from ethanol-consuming compared to control male rats. In contrast, no
      differences in the amplitude or conductance of I(Ca,L) were observed when
      comparing myocytes isolated from control and ethanol-consuming females. Ethanol
      treatment had no significant effects on the kinetics I(Ca,L) inactivation or on
      steady-state activation and inactivation in either gender. In conclusion, male
      but not female cardiomyocytes respond to chronic ethanol consumption with an
      increased I(Ca,L) that may represent a compensatory response to the depressed
      contractility.

PMID- 12791306
TI  - Direct cardiac effects of As2O3 in rabbits: evidence of reversible chronic
      toxicity and tissue accumulation of arsenicals after parenteral administration.
AB  - Although parenteral administration of As(2)O(3) is highly effective in the
      treatment of acute promyelocytic leukemia, cardiac toxicity has been reported.
      This study employed Langendorff perfusion to determine the direct effects of
      As(2)O(3) in the electrophysiological properties of rabbit hearts after acute or
      chronic As(2)O(3) treatment (0.2 mg/kg/day iv for 30 days). Tissue accumulations
      of arsenicals and pathological changes as well as the reversibility of chronic
      As(2)O(3) effects were assessed. We found that cardiac conduction and
      repolarization were not altered whatsoever after acute As(2)O(3) treatment at
      clinically relevant (1, 3, and 10 microM) and higher (30 microM) doses.
      Nevertheless, an extremely high concentration of As(2)O(3) (300 microM) prolonged
      the corrected QT interval. Subsequent to chronic As(2)O(3) administration and
      with 30 microM As(2)O(3) via Langendorff perfusion, polymorphic ventricular
      tachycardia was observed (1/7, 14%). Corrected QT interval was prolonged, while
      basic cycle length was shortened. Significant accumulation of arsenicals in the
      cardiac tissue was found, but without any pathological changes. After As(2)O(3)
      was discontinued for 30 days, the chronic As(2)O(3) -induced electrophysiological
      changes improved, no ventricular arrhythmia was noted, and the tissue
      concentration of arsenicals decreased considerably. We therefore conclude that,
      although no immediate cardiac effects were discemable at clinically relevant
      doses, an extremely high concentration of As(2)O(3) could prolong ventricular
      repolarization. Chronic As(2)O(3) treatment resulted in a prolonged ventricular
      repolarization, in association with arsenicals accumulation and with risk of
      ventricular tachycardia. These chronic cardiac toxicities and the tissue
      accumulation of arsenicals were, however, partially reversible after cessation of
      As(2)O(3).

PMID- 12791305
TI  - Effect of microcystin-LR and cyanobacterial extract from Polish reservoir of
      drinking water on cell cycle progression, mitotic spindle, and apoptosis in CHO
      K1 cells.
AB  - Microcystin-LR is a cyanobacterial toxin possessing a potent tumor-promoting
      activity mediated through inhibition of protein phosphatases PP1 and PP2A.
      Because these enzymes are involved in fundamental cell processes, we decided to
      examine the influence of microcystin-LR on cell cycle progression, onset of
      anaphase, segregation of chromosomes by the mitotic spindle, and apoptosis in
      Chinese hamster ovary (CHO-K1) cells. Cells were incubated with 25, 50, and 100
      microM of pure microcystin-LR and a cyanobacterial extract for 14, 18, and 22 h.
      Giemsa staining of cells treated with these toxins revealed a dose- and time
      dependent increase of mitotic indices, accumulation of abnormal G(2)/M figures
      with hypercondensed chromosomes, abnormal anaphases with defective chromosome
      separation, and polyploid cells. Because spindle checkpoint is a fundamental
      regulatory mechanism that assures the onset of anaphase and subsequent exit from
      mitosis, we examined the spindle organization in microcystin-treated cells. The
      majority of the mitotic cells showed monopolar and multipolar mitotic spindles
      (multiple asters). Microtubule bundles were present in interphase cells. Our
      results indicate that microcystin-LR induces apoptosis and necrosis in a dose-
      and time-dependent manner and that the frequency of dead cells cells is
      positively correlated with the frequency of polyploid cells.

PMID- 12791307
TI  - Quantitative structure-property relationships for physiologically based
      pharmacokinetic modeling of volatile organic chemicals in rats.
AB  - The objective of present study was to develop quantitative structure-property
      relationships (QSPRs) for the chemical-specific input parameters of rat
      physiologically based pharmacokinetic (PBPK) models (i.e., blood:air partition
      coefficient (P(b)), liver:air partition coefficient (P(l)), muscle:air partition
      coefficient (P(m)), fat:air partition coefficient (P(f)), and hepatic clearance
      (CL(h))), for simulating the inhalation pharmacokinetics of volatile organic
      chemicals (VOCs). The literature data on P(b), P(l), P(f), and P(m) for 46 low
      molecular-weight VOCs as well as CL(h) for 25 such VOCs primarily metabolized by
      CYP2E1 (alkanes, haloalkanes, haloethylenes, and aromatic hydrocarbons) were
      analysed to develop QSPRs. The QSPRs developed in this study were essentially
      multilinear additive models, which imply that each fragment in the molecular
      structure has an additive and constant contribution to partition coefficients and
      hepatic clearance. Most of the values in the calibration set could be reproduced
      adequately with the QSPR approach, which involved the calculation of the sum of
      the frequency of occurrence of fragments (CH(3), CH(2), CH, C, C=C, H, Cl, Br, F,
      benzene ring, and H in benzene ring structure) times the fragment-specific
      contributions determined in this study. The QSPRs for P(b), P(l), P(m), P(f), and
      CL(h) were then included within a PBPK model, which only required the
      specification of the frequency of occurrence of fragments in a molecule along
      with exposure concentration and duration as input for conducting pharmacokinetic
      simulations. This QSPR-PBPK model framework facilitated the prediction of the
      inhalation pharmacokinetics of four VOCs present in the calibration dataset
      (toluene, dichloromethane, trichloroethylene, and 1,1,1-trichloroethane) and four
      VOCs that were not part of the calibration set (1,2,4-trimethyl benzene, ethyl
      benzene, 1,3-dichloropropene, and 2,2-dichloro-1,1,1-trifluoroethane) but that
      could be described using the molecular fragments investigated in the present
      study. The QSPRs developed in this study should be potentially useful for
      providing a first-cut evaluation of the inhalation pharmacokinetics of VOCs prior
      to experimentation, as long as the number and nature of the fragments do not
      exceed the ones in the calibration dataset used in this study.

PMID- 12791308
TI  - An update on in vitro test methods in human hepatic drug biotransformation
      research: pros and cons.
AB  - The liver is the predominant organ in which biotransformation of foreign
      compounds takes place, although other organs may also be involved in drug
      biotransformation. Ideally, an in vitro model for drug biotransformation should
      accurately resemble biotransformation in vivo in the liver. Several in vitro
      human liver models have been developed in the past few decades, including
      supersomes, microsomes, cytosol, S9 fraction, cell lines, transgenic cell lines,
      primary hepatocytes, liver slices, and perfused liver. A general advantage of
      these models is a reduced complexity of the study system. On the other hand,
      there are several more or less serious specific drawbacks for each model, which
      prevents their widespread use and acceptance by the regulatory authorities as an
      alternative for in vivo screening. This review describes the practical aspects of
      selected in vitro human liver models with comparisons between the methods.

PMID- 12791309
TI  - IL-10, a key effector regulatory cytokine in experimental autoimmune
      encephalomyelitis.

PMID- 12791310
TI  - The role of interleukin 10 in the control of autoimmunity.

PMID- 12791311
TI  - Role of interleukin-10 in the induction and function of natural and antigen
      induced regulatory T cells.

PMID- 12791312
TI  - Interleukin-10 in the regulation of T cell-induced colitis.

PMID- 12791313
TI  - The complex role of interleukin-10 in autoimmunity.
AB  - Interleukin-10 (IL-10) is a cytokine that has been tested in different clinical
      trials based on its ability to down regulate T helper 1-type responses, namely
      IFN-gamma secretion and activation of monocytes/macrophages. There is also
      evidence in different animal models, that IL-10 could be useful in controlling
      Th2-mediated inflammatory processes. However, IL-10 also displays
      immunostimulatory properties especially on B cells and activated CD8(+)T cells.
      These seemingly divergent effects may explain the apparent lack of activity or
      adverse effects observed after IL-10 treatment in several animal models or
      clinical trials. Nevertheless, the ability of IL-10 to induce the differentiation
      of a subset of regulatory CD4(+)T cells (Tr1) and the importance of IL-10 for the
      in vivo function of regulatory T cells tends to support the view of IL-10 as a
      crucial cytokine in the control of immune responses. In different in vivo models,
      these cells were shown to inhibit Th1 and Th2-type inflammatory responses through
      the secretion of IL-10. These Tr1 cells may thus be used in specific cellular
      therapy in order to deliver IL-10 precisely at the site of inflammation.

PMID- 12791314
TI  - The role of interleukin-10 in systemic lupus erythematosus.

PMID- 12791315
TI  - Spontaneous increase of plasma-like cells with high GANP expression in the
      extrafollicular region of lymphoid organs of autoimmune-prone mice.
AB  - Autoimmune-prone mice bear a hyper-active B cell population generated
      spontaneously in peripheral lymphoid organs. Expression of beta RNA-primase GANP
      was shown to be an activation marker in lymphoid follicle germinal center (GC) B
      cells after immunization with T cell-dependent antigen (TD-Ag) in normal mice. In
      this study, we examined the expression of GANP in lymphoid tissues of autoimmune
      prone mice. GANP expression was up-regulated in GC-B cells after stimulation with
      TD-Ags; however, highly GANP-positive (GANP(hi)) cells were also observed in
      lymph nodes of non-immunized MRL/lpr mice. GANP(hi)cells in lymph nodes as well
      as in spleens of the different autoimmune-prone strains, MRL/lpr, NZB,
      (NZBxNZW)F1 and BXSB, gradually increased with age. This population was detected
      only in small numbers in the red pulp region of the spleen after immunization
      with TD-Ag in normal C57BL/6 and BALB/c mice. GANP(hi)cells had a B220(
      )IgM(+)Syndecan-1(+)phenotype, but were negative for PAS-staining and bromo
      deoxyuridine incorporation. These results demonstrate that GANP(hi)plasma-like
      cells appear in lymph nodes of autoimmune mice during aging, suggesting that the
      new plasma cell population might be generated after hyper-activation of B cells
      during the course of autoimmune disease.

PMID- 12791316
TI  - IL-1beta, IFN-gamma and TNF-alpha increase vulnerability of pancreatic beta cells
      to autoimmune destruction.
AB  - In the pathogenesis of type-1 diabetes insulin-producing beta-cells are destroyed
      by cellular autoimmune processes. The locality of beta-cell destruction is the
      inflamed pancreatic islet. During insulitis cytokines released from islet
      infiltrating mononuclear cells affect beta-cells at several levels. We
      investigated whether cytokine-induced beta-cell destruction is associated with
      changes in the expression of the surface receptors intercellular adhesion
      molecule (ICAM)-1 and Fas. Islets from diabetes-prone and congenic diabetes
      resistant BB rats were exposed to interleukin (IL)-1beta alone or in combination
      with interferon (IFN)-gamma plus tumour necrosis factor (TNF)-alpha. Cytokines
      decreased islet insulin content, suppressed glucose stimulated insulin secretion
      and generated enhanced amounts of nitric oxide and DNA-strand breaks. While no
      membrane alterations of IL-1beta treated islets cells were detectable, the
      cytokine combination caused damage of cell membranes. Independent of diabetes
      susceptibility IL-1beta treated islet beta-cells expressed a significantly
      increased amount of ICAM-1 on their surfaces which was not further increased by
      IFN-gamma+TNF-alpha. However, IL-1beta induced Fas expression was significantly
      enhanced only on beta-cells from diabetes-prone BB rats. From these results we
      suggest that IL-1beta mediates the major stimulus for ICAM-1 induction which is
      possibly a necessary but not sufficient step in the process of beta-cell
      destruction. Obviously, the additional enhancement of Fas expression on the
      surface of beta-cells is important for destruction. The combined action of all
      three cytokines induced the expression of Fas on the beta-cell surface
      independent of diabetes susceptibility, indicating that such a strong stimulus in
      vitro may induce processes different from the precise mechanisms of beta-cell
      destruction in vivo.

PMID- 12791317
TI  - T cells and autoantibodies to human HSP70 in type 1 diabetes in children.
AB  - We studied T-cell proliferative responses (stimulation index: SI) and
      autoantibodies to human HSP60, HSP70 and HSP90 proteins in 25 children (mean age
      10.1+/-3.8 years) newly diagnosed with Type 1 diabetes. The control group for T
      cells included 25 adults and three pediatric donors without Type 1 diabetes.
      Controls for antibodies included 10 pediatric subjects. The T-cell responses to
      HSP70 of the test group (mean SI=4.5+/-3.1) were significantly greater than those
      of the control group (meanSI=1.4+/-0.6; p<0.0001); the incidence of HSP70
      responders was (85%) compared to 14% in the control group. All but three of the
      Type 1 children who responded to HSP70 also responded to HSP60 (85%). The T-cell
      responses of the Type 1 group to HSP90 (mean SI=1.7+/-1.1) were similar to those
      of the control group (mean SI=1.5+/-0.7). We mapped HSP70 epitopes recognized by
      T cells in seven subjects using overlapping peptides of the molecule. Among the
      Type 1 subjects, IgG seropositivity was 45% to HSP60, 30% to HSP70, and 15% to
      HSP90. Thus, we conclude that children with newly diagnosed Type 1 diabetes
      manifest heightened T-cell autoimmunity to HSP70 and HSP60, but not to HSP90.

PMID- 12791318
TI  - Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted
      by peripheral blood mononuclear cells from patients with systemic lupus
      erythematosus.
AB  - Matrix metalloproteinase-9 (MMP-9) was involved in inflammation and immune system
      dysfunctions. Besides immunologic abnormalities, systemic lupus erythematosus
      (SLE) also presents chronic inflammatory components. Therefore, a role of MMP-9
      in SLE pathology might be supposed. To verify this hypothesis, SLE patients and
      healthy donors were compared for the MMP-9 and MMP-9 mRNA levels in peripheral
      blood mononuclear cells (PBMCs), the spontaneous secretion of MMP-9 and TIMP-1
      and the MMP-9 activity. Thus, we found that fresh PBMCs from SLE patients
      expressed a significantly higher activity of MMP-9 and spontaneously released
      higher levels of MMP-9, as compared to healthy donors, while the secreted TIMP-1
      level was the same for both groups. When the patients were sub-grouped based on
      disease status, the most increased pro-MMP-9 activity inside the PBMCs was
      identified for relapse SLE sub-group. A similar observation for SLE patients with
      positive serum fibrinogen was found. Following culture, the PBMCs from remission
      SLE patients secreted significantly higher MMP-9 level, than the PBMCs from
      relapse SLE patients. PBMCs from relapse SLE patients secreted the highest levels
      of TIMP-1, although this difference was not statistically significant. Taken
      together, these observations suggested the multiple roles of MMP-9 and TIMP-1 in
      progress of inflammation and tissue damage and/or in repair, depending on
      clinical stages of SLE.

PMID- 12791319
TI  - Fine specificity and subclasses of IgG anti-actin autoantibodies differ in health
      and disease.
AB  - Current opinions suggest that autoantibodies occurring in autoimmune diseases are
      generated by B-cells which primarily produce polyspecific natural autoantibodies,
      through either polyclonal activation or specific antigen selection of these B
      cells. In this study, we compared the immunological properties (polyspecificity,
      fine specificity and IgG subclasses) between natural anti-actin antibodies (N
      AAA) and disease-associated AAA (D-AAA). IgG AAA from sera of healthy donors,
      patients with autoimmune hepatitis type 1 (AIH-1) and patients with primary
      biliary cirrhosis (PBC) were affinity-purified on actin immunoadsorbent and
      tested initially for polyspecificity against various cytoskeleton proteins by
      enzyme-linked immunosorbent assay (ELISA). Fine specificity was studied by
      Western blotting using proteolytic peptides of actin and by ELISA using synthetic
      12 mer peptides, spanning the 221-377 aa sequence of actin. Results showed that
      both N-AAA and D-AAA are polyspecific. Nevertheless, D-AAA from both diseases
      showed a specific reactivity pattern as compared to N-AAA, against the 16 kDa C
      terminal (229-377 aa) proteolytic peptide of actin and more specifically against
      the P36 synthetic peptide (351-362 aa). Quantitation of AAA IgG subclasses
      revealed that IgG1 and IgG3 were specifically increased in D-AAA from AIH-1 and
      PBC, respectively, as compared to N-AAA. We conclude that D-AAA are
      differentiated from N-AAA in terms of fine specificity and IgG subclasses,
      probably through specific antigen selection of B-cells primarily producing N-AAA.

PMID- 12791320
TI  - Hemodynamic improvement and removal of autoantibodies against beta1-adrenergic
      receptor by immunoadsorption therapy in dilated cardiomyopathy.
AB  - The removal of beta(1)-adrenergic receptor (beta(1)AR) autoantibodies by
      immunoadsorption (IA) has been proposed as a potential mechanism for the
      improvement of the left ventricular function in dilated cardiomyopathy (DCM). In
      the present study, the possible association between removal of the autoantibodies
      against the human beta(1)AR with the hemodynamic improvement induced by IA was
      investigated.IA was performed in 22 DCM patients (n=22; NYHA III-IV, EF<30%,
      stable medication). The beta(1)AR autoantibodies from column eluents (CE) were
      detected by enzyme-linked immunosorbent assay (ELISA) and BIAcore methods. CE of
      32% (7/22) of the patients was found to be antibody-positive with ELISA or
      BIAcore. In addition, a bioassay system was also used for the detection of this
      autoantibody. Seventy-three percent (16/22) of the patients were found to be
      antibody-positive by this method. However, independent of the beta(1)AR antibody
      detection method, both antibody-positive and antibody-negative groups showed
      similar acute and prolonged hemodynamic improvements during IA therapy.
      Furthermore, antibody-positive and -negative groups received a comparable
      improvement of left ventricular ejection fraction. These results suggest that
      different mechanisms are involved in the hemodynamic improvement induced by IA.
      The beneficial hemodynamic effects induced by IA are not directly associated with
      the removal of beta(1)AR autoantibodies.

PMID- 12791322
TI  - Epilepsy self-management: a comparison of self-efficacy and outcome expectancy
      for medication adherence and lifestyle behaviors among people with epilepsy.
AB  - The purpose of this study was to describe self-efficacy beliefs and outcome
      expectancies toward medication, seizure, and lifestyle management behaviors among
      108 adults with epilepsy. Participants responded to an adapted version of the
      Epilepsy Self-Efficacy and Epilepsy Outcome Expectancy scales. Modifiable
      behavioral risk factors such as confidence for following medication dosing
      schedule, planning for medication refills, coping with adverse effects of
      medication, getting sufficient sleep, avoiding alcohol, and obtaining social
      support were identified. A larger proportion of persons reported higher self
      efficacy for medication management behaviors than for healthful lifestyle
      behaviors. Findings from this study extend previous research on chronic disease
      that showed that individuals may be adherent with medication therapy, but not
      with healthful lifestyle behaviors necessary for the prevention and treatment of
      chronic disease. Individuals with low self-efficacy would benefit from
      interventions that increase efficacy beliefs to enhance their ability to adopt
      and maintain good self-management practices.

PMID- 12791321
TI  - Psychogenic nonepileptic seizures: review and update.
AB  - The population incidence of psychogenic nonepileptic seizures (PNES) may be only
      4% that of epilepsy, but many patients with PNES have a tendency to seek medical
      attention, and PNES make up a larger share of the workload of neurologists and
      emergency and general physicians. Although a great number of publications
      describe how PNES can be distinguished from epileptic seizures, it usually takes
      several years to arrive at this diagnosis, and three-quarters of patients (with
      no additional epilepsy) are treated with anticonvulsants initially. However, the
      management of PNES as epileptic seizures can lead to significant iatrogenic harm.
      Moreover, the failure to recognize the psychological cause of the disorder
      detracts from addressing associated psychopathology and enhances secondary
      somatization processes. This review provides an overview of studies of the
      diagnosis, etiology, treatment, and prognosis of PNES. Physicians should always
      consider PNES in the differential diagnosis of a seizure disorder. If a diagnosis
      of PNES is possible, or a diagnosis of epilepsy in doubt, a clear diagnostic
      categorization should be sought. This should involve the assessment of the
      patient by a physician versed in the diagnosis of seizure disorders and, in many
      cases, the documentation of a typical seizure by video-EEG. Outcome may be
      improved if the diagnosis is more actively sought, made earlier, and communicated
      more convincingly.

PMID- 12791323
TI  - The impact of epilepsy on quality of life: a qualitative analysis.
AB  - The assessment and understanding of epilepsy's impact on an individual's quality
      of life (QOL) is increasingly being recognized as an important component of
      clinical care. Because the impact of epilepsy can span a range of clinically
      important functional and psychosocial domains, QOL as a model for understanding
      epilepsy's impact should be inclusive of the many life domains that are important
      to the individual. In this study a community-based sample of 46 adults with
      epilepsy were surveyed to identify the QOL domains that are important to persons
      with epilepsy, the factors that contribute to and detract from QOL, and the ways
      that epilepsy is perceived to impact QOL. A multidomain structure of quality of
      life emerged from the qualitative data analysis. Epilepsy was seen as having both
      a direct and an indirect impact on QOL, by directly affecting QOL domains and by
      affecting those factors that contribute to QOL.

PMID- 12791324
TI  - Volumetric evidence of a left laterality effect in epileptic psychosis.
AB  - We investigated anatomic alterations and lateralization effect in the mesial
      temporal lobe structures (amygdala and hippocampus) in epileptic psychosis MRI
      volumetric measurements. Patients with epileptic psychosis and normal controls
      were studied. Left hippocampus values were significantly smaller for patients
      (P<0.001). Hippocampal ratio was significantly greater for patients (P<0.01).
      Group (patients x normal) was the only factor explaining the statistically
      significant variation of left hippocampus and hippocampal ratio (P<0.001 and
      P<0.05). Twenty patients had hippocampal atrophy (4 on the right side, 15 on the
      left side, and 1 bilateral) associated with mesial temporal sclerosis. These
      results confirm the existence of anatomic alterations and a left laterality
      effect in the mesial temporal lobe structures of patients with epileptic
      psychosis.

PMID- 12791325
TI  - Psychogenic seizures: clinical features and psychological analysis.
AB  - Approximately 25-30% of patients referred to epilepsy centers for refractory
      epilepsy are found to have nonepileptic seizures (NES). In many cases
      psychological assessments are performed to evaluate for underlying psychiatric
      disorders. The authors analyzed the clinical features of 23 patients with NES and
      correlated the features with underlying psychological status. Thirteen of the
      twenty-three patients (56.5%) had motor manifestations and 10 presented with
      limpness and unresponsiveness. There was no significant difference in the
      occurrence of depression, anxiety, posttraumatic stress disorder, or malingering
      between patients with limpness and those with motor manifestations. However, only
      patients with motor manifestations had a history of sexual and physical abuse.
      Those with limp and unresponsive presentations were less likely to have a history
      of sexual and/or physical abuse. This finding may help treating physicians to
      choose optimum psychiatric treatment for patients with NES. Additional studies
      are needed to clarify the association.

PMID- 12791326
TI  - Hypothalamic hamartomas: seven cases and review of the literature.
AB  - Hypothalamic hamartomas constitute rare developmental lesions associated with
      gelastic epilepsy and/or precocious puberty (PP). We elected to review cases
      encountered at our center (7 patients) and the existing literature (277 patients)
      to obtain a better understanding of the clinical aspects, pathogenesis, and
      treatment of this entity. Evidence suggests that gelastic seizures are due to
      intrinsic epileptogenicity. The cause of the subsequent development of other
      seizure types, cognitive decline, and diffuse spike-and-wave pattern remains
      unresolved and is addressed. Anticonvulsants often fail to control seizures and
      different surgical options are available. Available evidence suggests that a
      resection through a subtemporal approach is best for lesions that are
      pedunculated or with a significant prepontine component, while a transcallosal
      approach is more appropriate for sessile lesions with an intraventricular
      component. Gamma knife surgery may be especially useful for small sessile
      lesions, failed partial resections, or patients not appropriate or refusing open
      surgery.

PMID- 12791327
TI  - The association of stigma with self-management and perceptions of health care
      among adults with epilepsy.
AB  - OBJECTIVE: The purpose of this study was to examine the perception of stigma
      among adults with epilepsy including its association with epilepsy self
      management and perceptions of health care. METHODS: Participants for the study
      were recruited from two epilepsy centers and a neurology clinic. Individuals
      agreeing to participate in the study were asked to complete three assessments
      each 3 months apart. Data were collected from 320 adult men and women with
      epilepsy; 314 provided responses on stigma and were included in this analysis.
      RESULTS: Participants ranged in age from 19 to 75 years (mean=43). Fifty percent
      of the sample was female, and 80% was white. The mean age of seizure onset was 22
      years, and 76% of participants reported having had a seizure within the past
      year. Analysis suggests levels of perceived stigma are similar for men and women
      and across ethnic and age groups. However, participants who were not married or
      living with a partner, were not working for pay, and had limited income reported
      higher levels of stigma than did married participants, those working for pay, and
      those in higher income brackets. Participants reporting higher levels of stigma
      included those who had their first seizure before the age of 50 and a seizure in
      the last year. Participants whose seizures interfered more with activities, who
      rated their seizures as under less control, and who were not legally able to
      drive also reported higher levels of stigma. Tests of association between stigma
      and health-related variables revealed that participants reporting higher levels
      of perceived stigma also reported lower levels of self-efficacy to manage
      epilepsy; more negative outcome expectancies related to treatment and seizures;
      and lower levels of medication management, medication adherence, and patient
      satisfaction. However, they also reported greater management of information
      related to seizures. In regression analysis, income, age at first seizure,
      seizures during the past year, lower self-efficacy, negative outcome expectancies
      for seizures, and less patient satisfaction explained 54% of the variance in
      perceived stigma. CONCLUSIONS: The results of the study suggest that perceived
      stigma is significant for people with epilepsy and is associated with factors
      that are known to be important in the management of epilepsy. Understanding who
      is at greatest risk for feeling stigmatized could lead to the development of
      preventive measures.

PMID- 12791328
TI  - Sexual outcome after epilepsy surgery.
AB  - The aim of this study was to provide a description of patient-perceived sexual
      change after temporal lobe resection (TLR) and extratemporal resection (ETR).
      Fifty-eight TLR and sixteen ETR patients completed a semistructured interview and
      questionnaire assessing sexual change after epilepsy surgery. Five areas of
      sexual functioning were addressed: sexual drive, thoughts/fantasies, interest,
      masturbation, and activity. Each patient's perception of sexual changes relative
      to perceived levels of normal functioning was assessed. Characteristically, the
      onset of sexual change occurred in the first three postoperative months and
      persisted to the time of interview. A postoperative sexual change was
      significantly more likely to be reported by patients who had undergone TLR (64%)
      than ETR (25%). In the TLR group, sexual change was significantly more frequent
      following right-sided resections. Marked sexual change occurred more frequently
      in females than males. Postoperative sexual change is an important outcome
      feature after epilepsy surgery. The predisposition of TLR patients to
      postoperative change provides further evidence for a temporal lobe contribution
      to sexual function.

PMID- 12791329
TI  - Level and contents of consciousness in connection with partial epileptic
      seizures.
AB  - The present study introduces concepts and methods that can be used in the
      systematic psychological study of a seizure, to gain more insight into the
      seizure as it is experienced by the patient and the significant other. Fourteen
      patients reported 40 descriptions of their subjective experiences during complex
      partial seizures. We analyzed the descriptions with respect to the temporal
      progression of the seizure and the level and contents of consciousness. There
      were three main findings: (1). We identified an impairment of the voluntary
      control of attention ("forced attention") that seems to characterize the early
      stages of the seizure in all patients. (2). Although most patients reported the
      total absence of consciousness, we identified a subgroup of patients with a
      fluctuating level of consciousness during the seizure. (3). The patients who
      reported some contents of consciousness during the seizure were found to usually
      experience internal mental images rather than other contents of consciousness
      (e.g., sensations or perceptions). We propose that use of a qualitative
      methodology for the psychological assessment of seizures could lead to a better
      understanding of seizures as experienced from the patient's perspective and
      thereby to improvements in the treatment of seizures.

PMID- 12791330
TI  - The effects of vagus nerve stimulation therapy on patients with intractable
      seizures and either Landau-Kleffner syndrome or autism.
AB  - Acquired and developmental comorbid conditions, including language and behavioral
      disorders, are often associated with epilepsy. Although the relationship between
      these disorders is not fully understood, their close association may indicate
      that they share common features, suggesting that these conditions may respond to
      the same therapies. Not only has vagus nerve stimulation (VNS) therapy been
      proven to reduce the frequency of pharmacoresistant seizures in epilepsy
      patients, but preliminary studies also indicate that VNS therapy may improve
      neurocognitive performance. On the basis of these findings, we hypothesized that
      VNS therapy would improve the quality of life of patients with either Landau
      Kleffner syndrome (LKS) or autism, independent of its effects on seizures. Data
      were retrospectively queried from the VNS therapy patient outcome registry
      (Cyberonics, Inc; Houston, TX, USA). A constant cohort of 6 LKS patients and 59
      autistic patients were identified. Among the LKS patients, 3 patients at 6 months
      experienced at least a 50% reduction in seizure frequency as compared with
      baseline. Physicians reported quality-of-life improvements in all areas assessed
      for at least 3 of the 6 children. More than half of the patients with autism
      (58%) experienced at least a 50% reduction in seizure frequency at 12 months.
      Improvements in all areas of quality of life monitored were reported for most
      patients, particularly for alertness (76% at 12 months). Although these
      preliminary findings are encouraging, a prospective study using standardized
      measurement tools specific to these disorders and a longer-term follow-up are
      necessary to better gauge the efficacy of VNS therapy among these patient
      populations.

PMID- 12791331
TI  - Psychopathological profile in patients with severe bilateral hippocampal atrophy
      and temporal lobe epilepsy: evidence in support of the Geschwind syndrome?
AB  - Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible
      causal element in various neuropsychiatric disorders, in particular depressive
      disorder and schizophrenia. To test the hypothesis that bilateral symmetrical
      severe volume loss of the hippocampi is of causal relevance to these psychiatric
      syndromes rather than an epiphenomenon we assessed the psychopathology in a group
      of patients with temporal lobe epilepsy (TLE) and very severe bilateral
      symmetrical hippocampal atrophy and compared it with that of a patient control
      group. Patients with TLE and hippocampal volumes smaller than three standard
      deviations below the mean of a control population were identified and compared
      with a matched patient population with normal hippocampal volumes.
      Psychopathology was assessed by blinded trained psychiatrists using the Present
      State Examination and Neurobehavioral Inventory. The prevalence of psychiatric
      syndromes was high in both patient groups; however, there was no significant
      difference between the two groups. With use of the more specific Neurobehavioral
      Inventory a psychopathological pattern reminiscent of the Geschwind syndrome
      emerged when patients with BHA were characterized by caregivers. While BHA does
      not result in an increased prevalence of specific psychiatric syndromes, specific
      symptoms that characterize the Geschwind syndrome like hypergraphia and
      hyposexuality might be pathogenically related to hippocampal atrophy.

PMID- 12791332
TI  - Relationship between depression and intractability of seizures.
AB  - Patients with epilepsy have a higher prevalence of depressive disorders than the
      general population, but the relationship between seizure rates and depression has
      not been adequately studied. We used the Beck Depression Inventory to evaluate
      depressive symptoms in 143 consecutive epilepsy patients from outpatient clinics.
      Patients who were seizure free more than 6 months were considered not
      intractable. Thirty-six percent were neither intractable nor depressed, 43% had
      intractable epilepsy and were not depressed, 10% had intractable epilepsy and
      were depressed, and 11% did not have intractable epilepsy and were depressed.
      Patients with epilepsy have a higher prevalence of depression than the general
      population, but the intractability of the seizure disorder does not seem to be an
      independent risk factor for the occurrence of depression. There is no
      relationship between the severity of depression and monthly seizure rate.

PMID- 12791333
TI  - Long-term outcome of vagus nerve stimulation for refractory partial epilepsy.
AB  - We assessed 1- and 2-year outcomes of specific seizure types, quality of life,
      depression, and anxiety among patients treated with vagus nerve stimulation (VNS)
      for refractory partial epilepsy. Patients completed a seizure questionnaire, the
      Quality of Life in Epilepsy-89 (QOLIE-89) questionnaire, the Beck Anxiety
      Inventory (BAI), and the Beck Depression Inventory (BDI) at baseline and 1 year,
      and 2 years after activation of VNS. VNS was associated with >or=50% reduction in
      total seizure frequency in 54% of patients at 1 year and 61% of patients 2 years
      post-VNS activation compared with baseline. No statistically significant changes
      from baseline to 12 or 24 months were found in mean quality of life, depression,
      or anxiety measures in the overall study population. Patients with at least 50%
      reduction in seizures had significant improvement in anxiety at 12 and 24 months
      compared with patients who did not have the same degree of seizure reduction.

PMID- 12791334
TI  - Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy
      Registry.
AB  - The objective of this study was to assess the safety of gabapentin (Neurontin)
      exposure in human pregnancy. Prospective and retrospective data concerning 51
      fetuses, including 3 twin gestations, were collected from 39 women with epilepsy
      and other disorders exposed to gabapentin during pregnancy. Data were collected
      and evaluated about the 44 live births, including maternal demographics,
      diagnosis, treatment and complications, and fetal complications and outcomes. The
      results of this study showed that the rates of maternal complication, cesarean
      section, miscarriage, low birth weight, and malformation were less than or
      similar to those seen in the general population or among women with epilepsy.
      Gabapentin exposure during pregnancy did not lead to an increased risk for
      adverse maternal and fetal events in this study. However, because of the small
      number of patients examined in this study, additional data from more pregnancies
      and outcomes are needed.

PMID- 12791335
TI  - The seizure prediction characteristic: a general framework to assess and compare
      seizure prediction methods.
AB  - The unpredictability of seizures is a central problem for all patients suffering
      from uncontrolled epilepsy. Recently, numerous methods have been suggested that
      claim to predict from the EEG the onset of epileptic seizures. In parallel, new
      therapeutic devices are in development that could control upcoming seizures
      provided that their onset is known in advance. A reliable clinical application
      controlling seizures, consisting of a seizure prediction method and an
      intervention system, would improve patient quality of life. The question
      therefore arises as to whether the performance of the seizure prediction methods
      is already sufficient for clinical applications. The answer requires assessment
      criteria to judge and compare these methods, but recognized criteria still do not
      exist. Based on clinical, behavioral, and statistical considerations, we suggest
      the "seizure prediction characteristic" to evaluate seizure prediction methods.
      Results of this approach are exemplified by its application to the "dynamical
      similarity index" seizure prediction method using 582 hours of intracranial EEG
      data, including 88 seizures.

PMID- 12791336
TI  - Clinical and EEG findings in six patients with altered mental status receiving
      tiagabine therapy.
AB  - Tiagabine (TGB), a novel GABA reuptake inhibitor antiepileptic drug, has been
      reported to induce nonconvulsive status epilepticus (NCSE) in patients with
      generalized or partial onset seizures. We describe six patients with refractory
      partial epilepsy treated with add-on TGB. They developed acute intermittent or
      progressive chronic confusion associated with diffuse slowing of the
      electroencephalogram (EEG), shortly after an increase in dose of TGB. This
      remitted in each situation after reduction of the daily dose. The possibility of
      nonconvulsive status epilepticus or toxic encephalopathy is discussed.

PMID- 12791337
TI  - Epilepsy, demonic possessions, and fasting: another look at translations of Mark
      9:16.

PMID- 12791338
TI  - Selective emotional detachment from family after right temporal lobectomy.
AB  - Behavioral changes, such as mood disorders, anxiety, psychosis, and nonepileptic
      seizures often occur after temporal lobectomy. We report a man who selectively
      lost emotional attachments to family members after right temporal lobectomy.
      However, emotional responsiveness to strangers was normal or increased.

PMID- 12791339
TI  - Amusia after right frontal resection for epilepsy with singing seizures: case
      report and review of the literature.
AB  - Although many authors consider aprosodia and amusia to be synonymous, they
      actually represent two distinct communication disorders. Amusia refers to a
      profound deficit involving musical abilities, whereas aprosodia refers to
      deficits regarding the emotional content of speech. Many authors have presumed a
      similar etiology and localization for these conditions and assumed that these
      disorders would not occur independently. We report the case of a 31-year-old
      choir director who developed amusia without aprosodia after a right frontal lobe
      resection for intractable seizures. His ictal onset manifested with rhythmic
      slapping of his thighs while communicating with melodic speech. Video EEG
      monitoring documented right hemispheric discharges that occurred simultaneously
      with this ictal behavior. While a right frontal lobe resection made him seizure
      free, his postoperative amusia was so profound that he could no longer continue
      his occupation as a choir director. This case suggests that the right frontal
      cortex has different sites for musical ability distinct from the centers
      regarding prosody. Patients scheduled to undergo right frontal lobectomy ought to
      be counseled regarding the potential loss of musical abilities.

PMID- 12791340
TI  - Transient Kluver-Bucy syndrome following complex partial status epilepticus.
AB  - The characteristic features of Kluver-Bucy syndrome include hypersexuality,
      hyperorality, placidity, hypermetamorphosis, visual agnosia, changes in dietary
      habits, and memory impairment. Human cases have been reported with herpes simplex
      encephalitis, head injury, Pick's disease, transtentorial herniation,
      adrenoleukodystrophy, and Reye's syndrome, all involving bilateral temporal lobe
      pathology. We present the case of a patient with no evidence of a structural
      lesion in the temporal lobes and behavioral changes consistent with Kluver-Bucy
      syndrome following complex partial status epilepticus.

PMID- 12791341
TI  - Modafinil for treatment of cognitive side effects of antiepileptic drugs in a
      patient with seizures and stroke.

PMID- 12791342
TI  - Controversies in the diagnosis and management of psychogenic pseudoseizures.
AB  - Since the advent of video-EEG telemetry studies (V-EEG) neurologists have become
      increasingly aware of psychogenic pseudoseizures (PPS) given the relatively high
      prevalence of these events among patients seen in epilepsy centers. The use of V
      EEG has been accepted as the gold standard study in establishing this diagnosis;
      some clinicians, however, have suggested that the clinical phenomena of PPS are
      so obvious in many patients that V-EEG may not be necessary. This is one of many
      controversial points that clinicians face when evaluating patients suspected of
      having PPS. In this article, we review some of these controversies, specifically
      the need for a video-EEG monitoring study in all patients suspected of having PPS
      and the role of induction protocols in the evaluation of PPS, the question of
      whether patients have any control over their events, and finally some of the
      therapeutic strategies for PPS including the need to limit these patients'
      driving privileges.

PMID- 12791343
TI  - More controversies on the treatment of psychogenic pseudoseizures: an addendum.
AB  - There is no shortage of controversies when it comes to psychogenic pseudoseizures
      (PPS). In this addendum to the Iriarte et al. paper [Epilepsy Behav 4 (2003)
      354], I review some controversial issues related to the treatment of PPS. First,
      I advocate the point that our first goal of therapy is not to attempt to stop the
      occurrence of PPS, but to ensure that patients and families have accepted that
      they do not suffer from epilepsy, because the most frequent cause of morbidity
      and mortality seen in these patients is related to their misdiagnosis as epilepsy
      patients and the resultant aggressive treatment in intensive care units.
      Remission of PPS should be our second goal! The second controversial point
      pertains to how long neurologists should continue to follow up patients after a
      diagnosis of PPS is reached, and I suggest some parameters to be used in reaching
      such decision. In the third controversial issue, I review the lack of
      communication between neurologists and psychiatrists exemplified by the
      misinterpretation by psychiatrists of the diagnostic value of video-EEG-telemetry
      studies and resulting mixed messages given to patients and families by
      neurologists and psychiatrists. The fourth controversial point pertains to the
      criteria to discontinue antiepileptic drugs after a diagnosis of PPS has been
      established. Finally, I discuss the timing of introducing a psychogenic cause
      during the presentation of the diagnosis to patient and family.

PMID- 12791344
TI  - Classics in epilepsy and behavior: commentary.

PMID- 12791345
TI  - Psychometric and adaptive abilities in epilepsy with differential etiology. 1966.

PMID- 12791346
TI  - Placebo effect in antiepileptic drug trials.

PMID- 12791347
TI  - Guidelines.

PMID- 12791348
TI  - Multiprofessional guidelines for the management of the patient with primary
      cutaneous squamous cell carcinoma.
AB  - These guidelines for management of primary cutaneous squamous cell carcinoma
      present evidence based guidance for treatment, with identification of the
      strength of evidence available at the time of preparation of the guidelines, and
      a brief overview of epidemiological aspects, diagnosis and investigation. To
      reflect the collaborative process for the UK, this article is subject to dual
      publication in the British Journal of Dermatology and the British Journal of
      Plastic Surgery.

PMID- 12791349
TI  - Reconstructive options in the treatment of osteoradionecrosis of the
      craniomaxillofacial skeleton.
AB  - Osteoradionecrosis (ORN) of the craniomaxillofacial skeleton is a serious and
      debilitating complication that can occur following radiation therapy in the head
      and neck. Patients require effective treatment, which eradicates diseased tissue
      and restores function with minimal additional morbidity in a single stage, a
      requirement fulfilled in many cases by free tissue transfer. In a 6-year period
      from 1994 to 1999, 21 patients with ORN were treated by wide resection and free
      flap reconstruction. The median interval between radiation therapy and ORN was 4
      years (range: 1-33 years). The median radiation dose was 6000cGy. The affected
      areas were the mandible (15 patients), the temporal bone (three patients), the
      maxilla (one patient), the cervical vertebrae (one patient) and the frontal bone
      (one patient). Clinical symptoms included pain, ulceration, a persistent draining
      fistula, exposure of bone or hardware, and pathological fracture or non-union of
      bone. Six patients had had previous unsuccessful attempts at conservative
      surgical resection. Ten patients had preoperative hyperbaric oxygen (HBO)
      therapy. A number of different flaps were used for reconstruction in these
      patients. These included free fibula flaps (13 patients), iliac crest flaps (two
      patients), scapula flaps (three patients) and rectus abdominis flaps (three
      patients). All patients achieved relief from their presenting symptoms and
      primary bone or wound healing. One flap (4.8%) was lost. This was successfully
      reconstructed in a subsequent procedure. There were three flap re-explorations,
      two for arterial thrombosis and one for venous thrombosis. Conservative measures,
      such as limited debridement and HBO therapy, may be effective in preventing the
      progression of ORN. However, they fail to eradicate established ORN, which
      requires radical surgical resection followed by functional reconstruction with
      well-vascularised tissue.

PMID- 12791350
TI  - Reconstruction of axillary scar contractures--retrospective study of 124 cases
      over 25 years.
AB  - We present a retrospective study of 134 axillae treated in 124 cases of axillary
      scar contractures with the use of skin grafts and various flaps over the last 25
      years in our department. Free skin grafts were performed in 25 axillae, and local
      flap transfers including skin elongation procedures such as z-plasty were
      performed in 76 regions. As regional flap transfers, i.e. pedicled axial local
      flap transfers, latissimus dorsi flaps, para-scapular flaps, superficial cervical
      artery flaps (SCA flap) and bilateral combined scapular flaps were used for the
      reconstruction of 23 severe axillary scar contractures. Free flaps and scarring
      flaps were also used for five severe contracture cases. The results were
      generally satisfactory, but five problematic cases and seven cases of recurrence
      were encountered. In this report, we classify axillary contractures into five
      types and present our conclusions on the criteria for selecting appropriate
      surgical methods according to contracture type. Our results suggest there are
      four key scar features to be considered in the selection of surgical methods for
      axillary reconstruction: (1) size; (2) depth; (3) location and (4) shape. We also
      discuss and evaluate the various methods of reconstruction.

PMID- 12791351
TI  - Congenital heart disease and associated malformations in children with cleft lip
      and palate in Pakistan.
AB  - Children with cleft lip and palate often have other associated malformations. The
      reported incidence and types of associated malformations vary between different
      studies. There is a great paucity of literature on the subject from the region in
      general and none from Pakistan at all. The purpose of this study was to assess
      the frequency of associated malformations, particularly congenital heart disease,
      in children with cleft lip and palate presenting to the Aga Khan University (AKU)
      and Murshid Hospital (MH). From 1st October 1999 to 31st March 2002, all children
      with cleft lip and palate who presented to AKU and MH were prospectively enrolled
      in the study group. Socio-demographic characteristics and a number of other
      variables were documented. All children underwent a thorough clinical examination
      and an echocardiogram as part of the study protocol. 123 children formed the
      study group. Thirty-five (29%) of these children were found to have associated
      malformations. The most common of these was congenital heart disease, which
      accounted for 51% of all associated malformations. Thirty percent of cleft palate
      children had associated anomalies while 27% of cleft lip, with or without cleft
      palate, children had associated anomalies. There was a significant association
      between children born of a consanguineous marriage and the risk of associated
      malformations (p-value: 0.001). Consanguinity was present in 74% of children with
      associated anomalies as compared to 40% of children with no associated anomaly.
      Dysmorphic features and the presence of associated anomalies were also
      significantly associated (p-value: 0.009). Dysmorphic features were present in
      46% of children with anomalies as compared to 21% of children with no associated
      anomaly. Fifty percent of children with associated anomalies had a low birth
      weight compared to 34% of children with no anomalies, but the difference was not
      statistically significant. The presence of consanguinity in a child with
      dysmorphic features should raise the suspicion of an associated anomaly. The
      likelihood of this being a cardiac defect is high and should be ruled out with a
      thorough clinical examination, supplemented with an echocardiogram in certain
      cases.

PMID- 12791352
TI  - Endoscopic dissection of recipient facial nerve for vascularized muscle transfer
      in the treatment of facial paralysis.
AB  - In order to prepare recipient facial nerve branches for neurovascular muscle,
      transfer in the treatment of facial paralysis, endoscopic facial nerve dissection
      was employed. Under endoscopy recipient facial nerve branches innervating the
      zygomaticus major muscle were successfully dissected. A stab incision was
      sufficient for nerve suture with the donor nerve. This method is preferable for
      young or female patients in whom conventional cheek incisions should be avoided.

PMID- 12791353
TI  - Curtain type combined pedicled reduction mammoplasty with internal suspension for
      extensive hypertrophic and ptotic breasts.
AB  - Correction of extensive hypertrophy and ptosis of the breast with a long distance
      between the jugular notch of the sternum and the nipple presents a number of
      surgical challenges: Maintaining adequate nipple-areola perfusion, preserving
      sensation and function, minimising scars, and forming a juvenile breast shape.
      The curtain type bipedicled mammoplasty with internal suspension combines the
      following procedures: the surface of the new breast is built entirely by a
      cranially based flap, thus avoiding a vertical scar and stabilising the
      periareolar wound. The nipple-areola is pedicled caudally as well as centrally,
      thus optimizing perfusion and maintaining sensation and the capacity for
      lactation. Fixing of deepithelialized skin stabilises the residual breast tissue
      at the thoracic wall and forms an internal suspension.

PMID- 12791354
TI  - Functional outcomes following surgical repair of wrist extensor tendons.
AB  - The long term results following the repair of open injuries to extensors carpi
      radialis longus and brevis and extensor carpi ulnaris have not previously been
      reported. A retrospective case note review was performed and patients were called
      back for assessment following surgical repair. Grip strength and pinch strength
      were reduced by 9.9% (p=0.017) and 11.5% (p=0.049). Wrist movement was also
      reduced. This demonstrates that the division of these tendons should not be
      regarded as trivial as they may have long-term adverse effects on wrist function.
      Information gained from this study may be beneficial in patient education at the
      time of injury and may provide useful information when preparing medico legal
      reports.

PMID- 12791355
TI  - Secondary procedures following digital replantation and revascularisation.
AB  - In this retrospective study, 79 digits of 55 patients received 102 secondary
      procedures following replantation. We divided the procedures into two groups,
      occurring before or after 2 months following replantation. The procedures in the
      early group were mainly for soft tissue coverage (92%), and those in that late
      group were mainly for tendon (67%) to improve function. Factors associated with
      higher incidence of early secondary procedures included multiple-finger injury,
      avulsion or degloving injury and level of injury proximal to zone III in finger
      replantation (p<0.05). However, younger patients and those with proximal level
      replantation in fingers had more late secondary procedures (p<0.05). Flexor
      tenolysis procedure significantly improved the digital function after
      replantation (p<0.05).

PMID- 12791356
TI  - Angiosarcoma of the breast: a 30 year perspective with an optimistic outlook.
AB  - The aim of this study was to investigate the incidence and clinicopathological
      features of angiosarcoma of the breast by focusing on those cases passing through
      a busy general teaching hospital over a 30 year period. A search was carried out
      of all cases in the files of the Department of Pathology of the Royal London
      Hospital from 1970 to 2000. Four cases were identified as primary angiosarcomas
      involving the breast. The medical and surgical histories, macroscopic and
      microscopic features and clinical outcome with long-term follow-up are described
      in each case. Similarities were identified, such as initial presentation with a
      'bruise' and a latent period before the diagnosis was established. Half of our
      cases followed irradiation for breast cancer. In all cases the prognosis after
      surgery was excellent. The rarity of primary mammary angiosarcoma was confirmed.
      In younger patients the lesion was not associated with previous radiotherapy, but
      the older patients presented after radiotherapy for adenocarcinoma of the breast.
      Although very uncommon, these tumours must be considered in the differential
      diagnosis, especially with the increasing use of fine-needle-aspiration and core
      biopsy for preoperative diagnosis. The prognosis after complete surgical excision
      may be better than generally believed.

PMID- 12791357
TI  - Subunits of the cheek: an algorithm for the reconstruction of partial-thickness
      defects.
AB  - Reconstruction of partial-thickness defects of the cheek can be challenging. In
      addition to maintaining function, the repair must restore contour, minimise donor
      site deformity and not distort the eyelid, mouth or jaw line. Since the demands
      for repair differ according to the site, so do the reconstructive options. To aid
      in selecting the best method, we classify the cheek into five subunits based on
      vascular anatomy and relevant landmarks. Based on our experience with 160
      patients over a 12 year period, we present an algorithm that helps to select the
      best reconstructive option for each site. This algorithm is easy to follow and
      conforms to anatomical principles.

PMID- 12791358
TI  - Microvascular histopathology in head and neck oncology.
AB  - A histological study of both recipient and flap vessels was performed in 30
      patients with head and neck cancer, and relevant preoperative risk factors were
      assessed. A total of 35 free flaps were transferred in 30 patients; 16 patients
      had preoperative radiotherapy, 13 were smokers, eight had hypertension and six
      had peripheral vascular disease. No significant venous pathology was found in
      either the flap or the neck veins. However, over two-thirds of the neck arteries
      and one-half of the flap arteries were found to have microscopic arterial
      pathology. The only pre-existing factor significantly influencing vessel
      pathology was hypertension (P=0.007). All flaps survived, although in two there
      was some loss of the skin paddle. This study reveals that the majority of
      patients undergoing microsurgery in the head and neck region have pre-existing
      arterial damage in both the flap and the recipient arteries, but this does not
      have a significant effect on the overall patency of the microvascular
      anastomoses.

PMID- 12791359
TI  - Otoplasty by percutaneous anterior scoring. Another twist to the story: a long
      term study of 114 patients.
AB  - A large number of techniques have been described for the correction of prominent
      ears to improve the cosmetic outcome and reduce the complication rates. The
      procedure favoured by the senior author brings together a number of refinements,
      notably, percutaneous anterior scoring using a modified green needle, control
      over the degree of fold created and a simple but effective dressing. 114
      consecutive patients underwent the correction of 214 ears, with a mean follow up
      of 3 years and 11 months (9 months to 9 years and 6 months). The senior author
      performed 100 of these procedures and supervised a senior trainee for the
      remainder. The mean patient age was 18 years 3 months (3 to 66 years). 57 males
      and 57 females. 56 general anaesthetic and 58 local anaesthetic. Post-operative
      complications were; haemorrhage, one ear (required a dressing change); infection,
      four ears (treated with antibiotics); hypertrophic scarring, two ears which
      settled (no keloid); recurrence one ear (repeated surgery); continued prominence
      six ears (two had repeated surgery). No prominent sutures, no anterior skin
      necrosis, no visible irregularity of the anterior surface of the cartilage and no
      haematoma occurred. We feel that the low complication rate is due to maximising
      the advantages and minimising the disadvantages of the different techniques and
      refinements. We recommend this technique for the routine correction of prominent
      ears due to a poorly formed antihelical fold or deep conchal bowl.

PMID- 12791361
TI  - The impact of immunohistochemistry on sentinel node biopsy for primary cutaneous
      malignant melanoma.
AB  - Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal
      disease in patients with malignant melanoma. Superselection of pathological nodes
      has allowed improved pathological staging of disease. The aim of this study was
      to look at the impact of immunohistochemistry on pathological staging of sentinel
      nodes. The first 100 patients undergoing SNB for primary cutaneous malignant
      melanoma were included in this study. Sentinel node harvesting was performed with
      the aid of preoperative lymphoscintigraphy and the intraoperative use of both a
      gamma probe and blue dye. If the sentinel nodes contained tumour on either
      routine pathology or immunohistochemistry, patients were offered a therapeutic
      lymph node dissection (TLND). Patients underwent no other treatment to the
      primary lymph node basin if the sentinel node was free of metastases. In all, 95
      patients had at least one node identified, and 25 were staged SNB positive and
      offered subsequent TLND. We found that 76% (19/25) of SNB positive patients were
      staged positive on routine pathology, and 24% (6/25) were staged with
      immunohistochemistry. Immunohistochemistry upstaged disease in 8% of patients
      (6/76). In all, 21 of the patients staged positive with SNB underwent TLND; 50%
      (8/16) of the patients staged sentinel node positive with routine pathology
      showed no further disease in the TLND, compared with 100% (5/5) of the patients
      staged sentinel node positive with immunohistochemistry only (P<0.05). Three
      patients have developed recurrence within the nodal basin following a negative
      SNB. The sensitivity of the procedure is currently 89% (25/28), with a mean
      follow-up of 24 months. Immunohistochemistry is an essential part of identifying
      micrometastasis in sentinel nodes, upstaging 8% of patients in our series.
      Patients with micrometastatic disease may well have a different prognosis from
      those with occult disease, and careful delineation of these patients is required
      to determine the prognostic influence of micrometastasis.

PMID- 12791360
TI  - A venturi based suction drainage system used in facelifts.
AB  - A method of drainage using the Venturi suction system has been used in 3124
      facelifts over an 18 year period. It has proven to be effective and safe and has
      reduced the degree of postoperative bruising and swelling in these patients.
      There have been no complications relating to the technique.

PMID- 12791363
TI  - Publication rates for abstracts presented at the British Association of Plastic
      Surgeons meetings: how do we compare with other specialties?
AB  - We present a retrospective study of the publication rates of articles presented
      to five meetings of the British Association of Plastic Surgeons between 1995 and
      1999. The PubMed database (http://www.ncbi.nlm.nih.gov/PubMed/) was searched
      using the presenter's name and key words from the abstract. Publication rates
      varied from 23% for the Winter Meeting of 1999 to 54% for the Winter Meeting of
      1997. The mean time lag from presentation to publication varied between 13 and 25
      months (range: 1-46 months). These results are comparable to those found in some
      other medical specialties.

PMID- 12791362
TI  - Preservation of the facial artery in excision of the submandibular salivary
      gland.
AB  - BACKGROUND: The accepted method for submandibular gland excision traditionally
      includes ligation of the facial artery (FA) as suggested by a host of surgical
      atlases. Preservation of the FA may be significant in reconstructive procedures
      of the head and neck and its ligation may altogether be obviated. OBJECTIVE:
      Prospective feasibility study of FA preservation in submandibular gland excision.
      MATERIALS AND METHODS: Patients undergoing excision of the submandibular salivary
      glands from September 1999 through August 2001 were prospectively included. The
      FA was dissected and only its glandular branches ligated. Exclusion criteria were
      primary benign or malignant tumors of the submandibular salivary gland or
      metastatic disease involving the gland or level I of the neck. In cases where the
      primary tumor involved the floor of mouth, anterior tongue or mandible, resection
      of level I contents included the FA even in N0 necks. RESULTS AND CONCLUSIONS:
      104 patients (116 procedures) were included in the study. 81 patients underwent
      resection of the gland with preservation of the FA. The vessel was sacrificed in
      35 necks because of metastases or primary tumor and in two cases of chronic
      sialadenitis. One patient had a postoperative hematoma following neck dissection
      requiring re-exploration. The source of bleeding was not found to be related to
      the FA. Contrary to accepted methodology, the FA may readily be preserved in
      surgery of the submandibular salivary glands. We suggest preservation of the FA
      in all cases of procedures for benign disease and in selected cases of
      malignancy.

PMID- 12791364
TI  - Phalangeal osteochondroma: a cause of childhood trigger finger.
AB  - Trigger finger is uncommon among children and often caused by various lesions. We
      report a 5-year old girl who presented with chronic painless triggering of the
      right ring finger and normal X-ray. She underwent exploration of the finger
      flexor tendons and release of the A1 pulley. Lack of obvious pathology dictated
      further wound exploration which revealed a hidden osteochondroma of the proximal
      phalanx. We believe that adequate surgical wound exposure is necessary if no
      obvious cause of triggering could be seen in order to rule out an atypical
      osteochondroma even in the presence of normal X-rays.

PMID- 12791365
TI  - Pseudo-tumoral proliferative nodule in a giant congenital naevus.
AB  - OBJECTIVE: To discuss the characteristics of proliferative nodules in giant
      congenital naevi. METHODS: We report the case of a newborn referred for staged
      curettage of a giant congenital naevus. A nodule was discovered on his left
      flank. It was excised for analysis during the first treatment session during the
      second week of life. RESULTS: The nodule was soft and looked like a lipoma. On
      optical microscopy however, there was a high cellular density and a high number
      of mitoses. Although the genetic analysis for melanoma antigens was reassuring, a
      firm nodule recurred a few days later. A second excision was performed at the
      fourth week. Surprisingly, on optical microscopy, the cellular density was much
      lower and there were no more atypias or mitoses; many neurotization foci were
      present. The natural history changed to spontaneous regression of the cellular
      activity. The diagnosis of proliferative nodule was made. CONCLUSION:
      Proliferative nodules in giant congenital naevi have specific clinical and
      histological characteristics. These should however be put into perspective. As
      demonstrated in this case, there can be an initial high mitotic activity within
      the nodule but this should not lead to the misdiagnosis of malignant melanoma.
      The spontaneous regression of cellular activity will allow the correct diagnosis
      to be made.

PMID- 12791366
TI  - A rare vasoproliferative lesion: angiolymphoid hyperplasia with eosinophilia of
      the hand.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vasoproliferative
      lesion of uncertain aetiology, involving the skin and subcutaneous tissue. The
      predilection of the tumour-like lesion is for the head and neck region. Radical
      surgical excision is still regarded as the most effective treatment. We present
      the case of a 33-year-old female with ALHE of the right hand. Preoperative MRI
      and angiography demonstrated involvement of the fourth and fifth rays, with
      complete occlusion of the ulnar artery, and a small lesion at the level of the
      metacarpophalangeal joint of the index finger. Complete tumour excision could not
      be achieved without resection of the fourth and fifth rays. One year
      postoperatively, there were no clinical signs of recurrence. The patient refused
      any further invasive diagnostic and follow-up examinations. Angiolymphoid
      hyperplasia of the hand is a rare disease, and patients should undergo early
      surgical treatment to achieve complete excision of the lesion.

PMID- 12791367
TI  - Malignant melanoma arising in a sebaceous nevus of the scalp.
AB  - This is the first report of malignant melanoma arising from sebaceous nevus (SN)
      of the scalp, although it has been known that various benign and malignant
      neoplasms may develop in association with SN. After the excisional biopsy for SN
      with 5 mm free margin, pathological examination revealed the coexistence of
      nodular melanoma invading to the reticular dermis (IV level of Clark) for a
      maximal depth of 4 mm. After resection with another 20 mm free margin, there has
      been no evidence of local recurrence or distant metastasis for nine years.

PMID- 12791369
TI  - Mucous cyst of the alar base: a rare complication following rhinoplasty.
AB  - Mucous cyst formation following rhinoplasty is a rare complication and typically
      presents late. Previously reported cases invariably involve the dorsum of the
      nose or nasal tip. We present a case where this unusual lesion was found to
      involve the alar base.

PMID- 12791368
TI  - Midline odontogenic infections: a continuing diagnostic problem.
AB  - Cutaneous sinus tracts and facial swellings of odontogenic origin have been well
      documented in the literature. These lesions however continue to be incorrectly
      diagnosed resulting in inadequate and unnecessary treatment. This paper reports
      two cases of midline odontogenic infections presenting as skin lesions. Neither
      patient complained of dental problems, and intraoral examination failed to reveal
      pathology. Both had been treated over an 18-month period, undergoing multiple
      surgical procedures before the correct diagnosis was made. Lesions on the face
      can be the result of occult chronic odontogenic infection. Awareness of a
      possible dental cause, especially with facial lesions that recur after excision
      is essential. The use of vitality testing of the teeth and appropriate
      radiographs ensures the correct diagnosis should not be missed.

PMID- 12791370
TI  - Massive osteolipoma of the skull.
AB  - Osteolipoma is a very rare condition, and only a few cases affecting the head
      were found in the literature. None can be compared with the giant lesion of the
      side of the head developing in the left temporo-parietal region of an 8-year-old
      boy from Central Africa. Under a huge lipoma, an irregular bony mass was found.
      Contouring resection was performed with an uneventful recovery. Technique and
      pathology are discussed.

PMID- 12791371
TI  - Autologous breast reconstruction with a free lumbar artery perforator flap.
AB  - Autologous breast reconstruction with a perforator flap has become increasingly
      popular. This paper presents the free lumbar artery perforator (LAP) flap as an
      option for breast reconstruction. Flap harvest is easy, no muscle is sacrificed
      and donor-site morbidity is minimal. Anastomosis of the sensory nerve to the
      fourth intercostal nerve is possible. The successful use of a LAP flap for breast
      reconstruction is illustrated with a case report, and the surgical technique is
      described. This method may be a good alternative for patients with relative
      contraindications to breast reconstruction with a DIEP flap.

PMID- 12791372
TI  - Intraneural ganglion cysts: a case of sciatic nerve involvement.
AB  - The pathogenesis of intraneural ganglion cysts is unknown. Some authors have
      established a connection between the cysts and the joint, while others have
      failed to find this communication. Most intraneural ganglion cysts occur in the
      proximity of a joint. We present the case of a 53-year-old Caucasian male with an
      intraneural cyst of the sciatic nerve located high above its bifurcation and
      without a connection to the joint. The lesion was microsurgically removed in
      toto. There was no recurrence of the cyst at follow-up 9 months postoperatively;
      complete resolution of the clinical symptoms occurred within 8 months of surgery.
      This case shows that ganglion cysts can occur in locations far from a joint,
      supporting the extra-articular embryonic synovial remnant theory of their
      genesis.

PMID- 12791373
TI  - Appropriateness of MRI scanning in the detection of ruptured implants used for
      breast reconstruction.
AB  - This case report highlights the problems associated with ruptured silicone breast
      implants used for breast reconstructive purposes. The patient originally
      presented with vague symptoms and signs to her GP and was extensively
      investigated over a period of years for left-sided chest/abdominal pain. Two
      separate scanning modalities were used prior to her being seen by either of the
      main authors and although none were employed specifically to assess for implant
      rupture, neither detected any free silicone around the hemithorax. The authors
      suggest that patients who have undergone breast reconstruction with a silicone
      implant may present in a manner not suggestive of implant damage. In such cases,
      where the silicone can extend over larger anatomical distances and where side
      effects can be damaging the investigation of choice should be MRI scanning which
      has a greater accuracy for detecting free silicone and defining the extent of
      spread.

PMID- 12791374
TI  - Haematoma as a late complication after breast reconstruction with implant.
AB  - We report a patient who, 3 1/2 years after mastectomy and breast reconstruction
      using a Becker implant, developed haematoma around the implant. We believe this
      is the first description of late haematoma formation in association with tissue
      expander (Becker implant), the differential diagnosis of which includes
      infection, recurrent cancer and implant rupture.

PMID- 12791375
TI  - Free DIEP flap breast augmentation following excessive reduction.
AB  - A two-stage procedure using bilateral free DIEP flaps to correct excessive
      bilateral breast reduction is described. The reconstructive challenge was to
      achieve satisfactory breast projection on a large torso without recourse to
      prosthetic implants or extensive back scars. The literature on the use of TRAM
      and latissimus dorsi flaps in subtotal breast reconstruction for various other
      breast deformities is reviewed. We have not found a similar case to ours in the
      literature.

PMID- 12791376
TI  - Idiopathic purpura fulminans and varicella gangrenosa of both hands, toes and
      integument in a child.
AB  - Chicken pox is a common childhood illness and, though a vaccine is readily
      available, it is not routinely included in the vaccination schedule of most
      countries owing to its mild clinical nature. However, varicella gangrenosa is a
      rare complication of this disease, infrequently reported in the literature. We
      report the case of a child who developed purpura fulminans in the convalescent
      phase of chicken pox and subsequently presented with peripheral gangrene of both
      hands and the toes of the right foot, and skin gangrene. To our knowledge,
      bilateral gangrene of the hands has rarely been reported, and we present this
      case to highlight the serious nature of complications following varicella
      infection.

PMID- 12791377
TI  - Following in the footsteps of the pharaohs.

PMID- 12791379
TI  - The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases.

PMID- 12791378
TI  - Re-examination of the significance of nuclear localization of PLCbeta1 in the
      likelihood of its involvement in neoplastic cell growth.

PMID- 12791380
TI  - Inhibitors of diverse metabolic steps cause increased apoptosis in deoxyadenosine
      resistant mouse leukemia L1210 cells that lack p53 expression: convergence at
      caspase-3 activation.

PMID- 12791381
TI  - Targeting signal transduction.

PMID- 12791383
TI  - Opportunities for studying cancer by metabolomics: preliminary observations on
      tumors deficient in hypoxia-inducible factor 1.

PMID- 12791382
TI  - Utilization of the promoter region of the midkine gene as a tool to drive
      therapeutic genes in a tumor specific manner.

PMID- 12791384
TI  - Structural and mechanistic aspects of phospholipase Cgamma regulation.

PMID- 12791385
TI  - Phospholipase Cdelta4: from genome structure to physiological function.

PMID- 12791386
TI  - Activation of PI(4)P 5-kinase by small G proteins.

PMID- 12791387
TI  - Importance of phase 2 gene regulation in protection against electrophile and
      reactive oxygen toxicity and carcinogenesis.

PMID- 12791388
TI  - Ferritin regulation by oxidants and chemopreventive xenobiotics.

PMID- 12791389
TI  - The regulation of adipocyte metabolism and gene expression by interleukin-11.

PMID- 12791390
TI  - A comprehensive model for the allosteric regulation of Class Ia ribonucleotide
      reductases.

PMID- 12791391
TI  - Raf kinases in lung tumor development.

PMID- 12791392
TI  - Interaction of cofilin with the serine phosphatases PP1 and PP2A in normal and
      neoplastic human T lymphocytes.

PMID- 12791393
TI  - Regulation of cell survival by atypical protein kinase C isozymes.

PMID- 12791394
TI  - Regulation of cytosolic phospholipase A(2) translocation.

PMID- 12791395
TI  - On the mechanism coupling phospholipase Cgamma1 to the B- and T-cell antigen
      receptors.

PMID- 12791396
TI  - Interpretive proteomics--finding biological meaning in genome and proteome
      databases.

PMID- 12791397
TI  - Clostridium perfringens iota-toxin, ADP-ribosyltransferase: structure and
      mechanism of action.

PMID- 12791398
TI  - Dissection of signal-regulated transcriptional modules by signaling pathway
      interference in oncogene-transformed cells.

PMID- 12791399
TI  - New cysteine protease inhibitors in physiological secretory fluids and their
      medical significance.

PMID- 12791400
TI  - At the nucleus of the problem: nuclear proteins and disease.

PMID- 12791401
TI  - Proceedings of the Forty-Third International Symposium on Regulation of Enzyme
      Activity and Synthesis in Normal and Neoplastic Tissues. Indianapolis, Indiana.
      September 23-24, 2002.

PMID- 12791403
TI  - Transmission and storage of medical images with patient information.
AB  - Digital watermarking is a technique of hiding specific identification data for
      copyright authentication. This technique is adapted here for interleaving patient
      information with medical images, to reduce storage and transmission overheads.
      The text data is encrypted before interleaving with images to ensure greater
      security. The graphical signals are interleaved with the image. Two types of
      error control-coding techniques are proposed to enhance reliability of
      transmission and storage of medical images interleaved with patient information.
      Transmission and storage scenarios are simulated with and without error control
      coding and a qualitative as well as quantitative interpretation of the
      reliability enhancement resulting from the use of various commonly used error
      control codes such as repetitive, and (7,4) Hamming code is provided.

PMID- 12791404
TI  - Computer assisted evaluation of wound healing in chronic ulcers.
AB  - The aim of this work was to present an efficient and objective method of wound
      healing assessment based on serial measurements of ulcer dimensions and
      calculation of wound margin advancement towards the center of the lesion. The
      method is implemented via computer software, which permits clinicians to perform
      necessary computations. The proposed method of wound assessment integrates pieces
      of work that have been published in the past into a user-friendly environment.
      The high accuracy of computations may help clinicians to make objective decisions
      in the management of difficult to heal ulcers.

PMID- 12791405
TI  - An intelligent system for diagnosis of the heart valve diseases with wavelet
      packet neural networks.
AB  - In this paper, an intelligent system is presented for interpretation of the
      Doppler signals of the heart valve diseases based on the pattern recognition.
      This paper especially deals with combination of the feature extraction and
      classification from measured Doppler signal waveforms at the heart valve using
      the Doppler Ultrasound. Because of this, a wavelet packet neural network model
      developed by us is used. The model consists of two layers: wavelet and multi
      layer perceptron. The wavelet layer is used for adaptive feature extraction in
      the time-frequency domain and is composed of wavelet packet decomposition and
      wavelet packet entropy. The multi-layer perceptron used for classification is a
      feed-forward neural network. The performance of the developed system has been
      evaluated in 215 samples. The test results showed that this system was effective
      in detecting Doppler heart sounds. The correct classification rate was about 94%
      for abnormal and normal subjects.

PMID- 12791406
TI  - Detection of ophthalmic artery stenosis by least-mean squares backpropagation
      neural network.
AB  - Doppler ultrasound is a noninvasive technique that allows the examination of the
      direction, velocity, and volume of blood flow. In this study, ophthalmic artery
      Doppler signals were obtained from 105 subjects, 48 of whom had suffered from
      ophthalmic artery stenosis. A least-mean squares backpropagation neural network
      was used to detect the presence or absence of ophthalmic artery stenosis.
      Spectral analysis of ophthalmic artery Doppler signals was done by the Welch
      method for determining the neural network inputs. The network was trained, cross
      validated and tested with subject records from the database. Performance
      indicators and statistical measures were used for evaluating the neural network.
      Ophthalmic artery Doppler signals were classified with the accuracy varying from
      88.9% to 90.6%.

PMID- 12791407
TI  - A computer model for the study of breast cancer.
AB  - A computer model was designed as a relational database to assess breast cancer
      screening in a cohort of women where the growth and development of breast cancer
      originates with the first malignant cell. The concepts of thresholds for growth,
      axillary spread, and distant sites are integrated. With tumor diagnosis, staging
      was performed that includes clinical and sub-clinical states. The model was
      parameterized to have staging characteristics similar to data published by the
      Surveillance, Epidemiology, and End-Results (SEER) Program. Validation was
      accomplished by comparing simulated staging results with non-SEER sources, and
      simulated survival with independent clinical survival data.

PMID- 12791408
TI  - Use of neural networks for dosage individualisation of erythropoietin in patients
      with secondary anemia to chronic renal failure.
AB  - The external administration of recombinant human erythropoietin is the chosen
      treatment for those patients with secondary anemia due to chronic renal failure
      undergoing periodic hemodialysis. The goal is to carry out an individualised
      prediction of the erythropoietin dosage to be administered. It is justified
      because of the high cost of this medication, its secondary effects and the
      phenomenon of potential resistance which some individuals suffer. One hundred and
      ten patients were included in this study and several factors were collected in
      order to develop the neural models. Since the results obtained were excellent, an
      easy-to-use decision-aid computer application was implemented.

PMID- 12791409
TI  - Characterization of arterial stenosis and elasticity by analysis of high
      frequency pressure wave components.
AB  - We describe a novel method for assessing stenosis severity based on pressure wave
      measurements. Pressure waves for several degrees of stenosis at different
      distances proximal to the stenosis were recorded from in vitro and in vivo
      models. Signal analysis was performed using power spectral density, and radial
      compliance was also measured. Pressure wave components at the acoustic frequency
      band (400-2500Hz) changed gradually and were dependent upon the distance from the
      stenosis and its severity. The shift of the pressure components could also
      demonstrate the elastic properties of tubes and arteries and explain the effect
      of a bifurcation in the system.

PMID- 12791410
TI  - Intestinal absorption of cephalexin in diabetes mellitus model rats.
AB  - We investigated the intestinal absorption and pharmacokinetics of cephalexin, as
      well as the intestinal H+/oligopeptide transporter PEPT1 mRNA and protein levels
      in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum
      loop was significantly lower in streptozotocin-induced type 1 diabetic rats and
      higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa/fa (Zucker) rats,
      than in control rats. These results were speculated to be due to the enhancement
      of intestinal absorption of cephalexin in GK and Zucker rats. Intestinal PEPT1
      mRNA levels were not significantly different between control and diabetic rats;
      however, the brush-border membrane vesicle PEPT1 protein levels were increased in
      GK and Zucker rats. After oral administration of cephalexin, plasma cephalexin
      concentrations and pharmacokinetic parameters, area under the concentration
      versus time curve from 0 to infinity, AUC(0-->infinity), and maximum plasma
      concentration, Cmax, in GK and Zucker rats were markedly higher than in control
      rats. From these findings, it is considered that intestinal absorption of drugs
      mediated by PEPT1 may be enhanced in hyperinsulinemic type 2 diabetes mellitus
      rats.

PMID- 12791411
TI  - Extended release lipophilic indomethacin microspheres: formulation factors and
      mathematical equations fitted drug release rates.
AB  - Extended release liphophilic microspheres of indomethacin were prepared using
      cetostearyl alcohol (CsA), stearyl alcohol (SA) and cetyl alcohol (CA) in the
      various drug-lipid ratios. The release of indometacin was studied on the basis of
      USP criteria and the effects of drug-lipid ratio, the size of microspheres and
      carboxymethylcellulose sodium (CMC-Na) added as a hydrophilic polymer on the drug
      release were investigated. In vitro dissolution studies were performed using USP
      XXIII apparatus I at pH 6.2. Release profiles were evaluated according to first
      order, Higuchi square root of time and Hixson-Crowell cube root models. The best
      fit was found with the square root of time model (r2=0.991) for the microspheres
      (125-250 microm) prepared in 1:4:1 drug-lipid-copolymer ratio using stearyl
      alcohol. With a further regression analysis, an excellent equation (Release%=
      10.721+42.549*square root of (t)-4.027*t) was developed for empirical drug
      estimation (r2=0.998).

PMID- 12791413
TI  - Design and evaluation of sustained release microspheres of potassium chloride
      prepared by Eudragit.
AB  - The aim of the present work was to prepare and evaluate the sustained release of
      potassium chloride formulations. Eudragit RS and/or RL loaded with potassium
      chloride microspheres were prepared by a solvent evaporation method. The effect
      of sustained release of Eudragit microspheres was evaluated by an in vitro
      dissolution test and in vivo oral absorption study, and the results were compared
      to a commercial product (Slow-K). The results showed that Eudragit microspheres
      loaded with potassium chloride can be easily prepared and satisfactory results
      obtained considering the size distribution and shapes of microspheres by
      incorporating aluminum stearate. The encapsulation efficiency and loading
      capacity were about 84-90% and 27%, respectively. Moreover, the Eudragit RS (30
      45 mesh) and Eudragit RS/RL (20-30 mesh) microspheres showed a similar sustained
      release effect of commercial product via in vitro dissolution and in vivo oral
      absorption study.

PMID- 12791412
TI  - Pharmacokinetics, in-situ absorption and protein binding studies of a new
      neuroleptic agent centbutindole in rats.
AB  - The present study reports the absorption kinetics, plasma protein binding and
      pharmacokinetic profile of the centbutindole (I) after i.v. and oral dosing in
      rats. In addition, an in-situ absorption study was carried out using a closed
      loop technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 was 5-fold
      less compared to that observed at pH 7.4. In-vitro and in-vivo protein binding
      (ultra filtration technique) was independent of substrate concentration over a
      range of 1.25-10.0 microg/ml. Pharmacokinetic parameters of I were determined in
      male rats after administering a single 4 mg/kg oral dose and 2 mg/kg intravenous
      dose. The peak serum concentration of I was found to be 50.1 ng/ml at 30 min
      after oral administration followed by a secondary Cmax of 43.2 ng/ml at 180 min.
      For the hydroxy metabolite (II), a Cmax of 6.4 ng/ml was measured at 360 min
      after oral administration of I. After oral dosing an irregular concentration-time
      profile with secondary peaks was observed for both I and II. The terminal half
      lives for I and II after oral dosing were 163 and 263 min, respectively. After
      intravenous dosing, the levels of I decreased biexponentially with a distribution
      (t(1/2) alpha) and elimination (t(1/2) beta) half-lives of 5.7 and 128 min,
      respectively. Comparison of the AUC after oral and intravenous dosing of I
      indicates that only about 24% of the oral dose reaches the systemic circulation.
      The limited bioavailability can either be due to the poor solubility of the
      compound and/or extensive first pass metabolism in the gastrointestinal (GI)
      tract. Co-administration of polyethylene glycol (PEG) at oral dosing improves
      solubilization and increases bioavailability.

PMID- 12791414
TI  - Thermal and rheological study of lipophilic ethosuximide suppositories.
AB  - We have performed thermal (differential scanning calorimetry) and rheological
      studies in the preformulation phase of ethosuximide suppositories to determine
      the influence of the active ingredient and adjuvants on the melting
      characteristics and rheological performance of the suppositories. Both types of
      studies were performed on the fatty bases witepsol H-19 and suppocire AP, each
      mixed with 5% w/w polysorbate 80, 0.1% w/w docusate sodium and 3% w/w tetranyl AT
      1/DP and on the suppository formulations obtained by the addition of 150 mg of
      ethosuximide to these excipients. Pure lipophilic excipients have two peaks in
      the DSC curve. The first one occurs at lower temperatures (27.35 degrees C for
      the suppocire AP and 34.3 degrees C for the witepsol H19) and the second peak at
      higher temperatures (36.27 and 35.95 degrees C for the suppocire AP and witepsol
      H19, respectively). Polysorbate 80, docusate sodium and tetranyl AT-1/DP cause
      the first melting peak to disappear and the second peak to occur at a lower
      temperature. The thermograms of the formulas show two melting peaks and the
      endothermic peak does not appear due to the melting of ethosuximide (47.8 degrees
      C). We attribute this behavior to the solubility of the drug in the melted
      excipient, thus originating a decrease of the melting temperature of the second
      peak in the DSC scan. The excipients and formulations behave as Newtonian fluids
      and the influence of ethosuximide and adjuvants can be noted in an increase in
      the viscosity of the suppository mass.

PMID- 12791415
TI  - Cross-linking of hard gelatin carbamazepine capsules: effect of dissolution
      conditions on in vitro drug release.
AB  - The aim of this study was to determine if the use of both enzyme and surfactant
      in the dissolution medium changes the in vitro drug release from cross-linked
      hard gelatin capsules containing a water-insoluble drug. Hard gelatin capsules
      were cross-linked by a controlled exposure to formaldehyde resulting in different
      stressed capsules and carbamazepine (CBZ) was chosen as a drug model. In vitro
      dissolution studies were conducted using simulated gastric fluid (SGF) and
      simulated intestinal fluid (SIF) with enzymes. Sodium lauryl sulfate (SLS) was
      added in the dissolution medium at a concentration of 2% m/v both in SGF and SIF
      with pepsin and pancreatin, respectively. The percentage of CBZ dissolved was
      reduced by increasing the degree of gelatin cross-linking. For unstressed hard
      gelatin capsules, 36% of the CBZ was released after 1 h, lowering to 5% for
      highly stressed hard gelatin capsules in the SGF. A similar effect was observed
      with SIF. In the case of moderately stressed hard gelatin capsules, addition of
      enzyme in the dissolution medium enhanced the percentage of CBZ dissolved. The
      dissolution level increased from 12% to 39% in SGF with pepsin for hard gelatin
      capsules cross-linked with 1500 ppm formaldehyde. On the contrary, the use of
      enzyme in the dissolution medium did not increase the dissolution of CBZ from
      highly stressed hard gelatin capsules. Surprisingly, the addition of SLS in the
      medium did not allow the release of the CBZ both in SGF and in SIF. The results
      of this study demonstrate that the use of enzyme in the dissolution medium is
      justified for moderately cross-linked hard gelatin capsules. However, the action
      of a surfactant added in the medium containing enzyme remains unclear.

PMID- 12791416
TI  - Arbekacin is actively secreted in the rat intestine via a different efflux system
      from P-glycoprotein.
AB  - This study was undertaken to examine the secretory transport of arbekacin, an
      aminoglycoside antibiotic, in the rat small intestine and to compare it with
      those in Caco-2 and LLC-PK1 cells. In vitro permeation of arbekacin was examined
      using an Ussing chamber technique. Serosal-to-mucosal (secretory)/mucosal-to
      serosal (absorptive) permeation ratios of 0.5 mM arbekacin were 2.8 in the
      jejunum and 7.0 in the ileum, respectively, indicating that arbekacin permeation
      was highly secretory-oriented. In the ileum, the ratios became smaller with
      increase in arbekacin concentration applied. When D-glucose was replaced with 3-o
      methyl-D-glucose in the experimental medium, the directionality of the arbekacin
      permeation disappeared almost completely. Absorptive permeation of arbekacin was
      not significantly influenced by verapamil, cyclosporin A, or probenecid. On the
      other hand, when gentamicin sulfate was added to the serosal medium, secretory
      transport of arbekacin was significantly inhibited. The results of this study
      strongly suggest that a specialized efflux system other than P-glycoprotein and
      multidrug resistance proteins was involved in the secretory transport of
      arbekacin in the rat intestine. There was no directionality in arbekacin
      permeation across Caco-2 cell monolayers, suggesting the absence or very slight
      expression of the secretory system for arbekacin in this cell line.

PMID- 12791417
TI  - Pharmacodynamics of NN2211, a novel long acting GLP-1 derivative.
AB  - OBJECTIVE: To evaluate the effects of NN2211, a GLP-1 derivative, on glucose and
      insulin homeostasis in healthy volunteers by use of a nonlinear mixed-effects
      modeling approach. DESIGN: NN2211 is a GLP-1 derivative intended for the
      treatment of type 2 diabetes. In the present study, eight dose levels of NN2211
      were tested in healthy human volunteers. Since NN2211 is only intended to have an
      effect when glucose levels are above baseline (thus limiting the risk of
      hypoglycaemia), no effects would be expected in healthy volunteers. In order to
      demonstrate effect in a phase 1 study including only healthy subjects, a glucose
      dose was administered i.v. 9 h after NN2211 dosing; the insulin response would
      then be expected to be improved (higher) in the subjects dosed with NN2211.
      METHODS: In the present work, the pharmacodynamic glucose and insulin response
      was modeled by fitting glucose and insulin data simultaneously with a nonlinear
      model incorporating known carbohydrate regulation mechanisms. After an initial
      model-building phase, the first-order approximation to the likelihood available
      in NONMEM was used to model the data. Placebo-dosed subjects were included in the
      analysis. RESULTS: It was possible to satisfactorily fit both insulin and glucose
      data simultaneously. The analysis demonstrated a dose proportional effect of
      NN2211 on the parameters controlling beta cell insulin secretion.

PMID- 12791418
TI  - Novel high energy intermediate analogues with triazasterol-related structures as
      inhibitors of ergosterol biosynthesis. III. Synthesis and antifungal activity of
      N4-alkyl-1,6,7,11b-tetrahydro-2H-pyrimido[4,3-a]isoquinolin-4-amine salts.
AB  - A series of N4-alkyl-1,6,7,11b-tetrahydro-2H-pyrimido[4,3-a]isoquinolinamine
      hydroiodides with triazasterol-related structures was designed and synthesized to
      mimic, as stable analogues, native high energy intermediates (HEI) of ergosterol
      biosynthesis. The title compounds can be regarded as 8,13,15-triaza-13,17
      secosteroids with aromatic ring A bearing the positive charge in the guanidinium
      moiety. Hence, these compounds present structural similarities with corresponding
      carbocationic intermediates occurring during the enzyme catalyzed transformation
      of squalene into ergosterol. The N4-alkylaminopyrimidoisoquinolinium salts were
      prepared by reaction of respective S-methylthiotetrahydropyrimidoisoquinoline
      hydroiodides with octylamine, and appropriately methyl-branched alkyl- and
      alkenylamines. In order to prepare (3R)-6-isopropyl-3-methyl-6-hepten-1-amine
      several synthetic routes were investigated. The structures of all reported
      compounds were proved and completely assigned on the basis of homo- and
      heteronuclear correlated 1D and 2D NMR spectroscopy. The in vitro antifungal
      susceptibility tests of the title compounds with a standard panel of eight
      pathogenic fungi revealed especially against the used dermatophytes and yeasts
      with MICs in the range of 1-32 microg/ml moderate to good antimycotic effects.
      Depending on the nature of the N4-alkyl substituents structure-activity
      relationships were found with a maximum of antifungal efficacy of the N4-3,7
      dimethyloctylaminopyrimidoisoquinolinium iodide.

PMID- 12791419
TI  - Breast cancer in the older woman.

PMID- 12791420
TI  - Geriatric oncology.
AB  - The discussion of breast cancer in the older woman implies an outline of unique
      aspects of cancer and aging. In this analysis, five aspects are highlighted
      because they pertain to breast cancer control: the diversity of the older
      population; the age-related increase in cancer susceptibility; the changes in
      tumor biology that occur with aging; and the implication of these factors for the
      prevention and treatment of cancer. The comprehensive geriatric assessment
      accounts for the diversity of the older population in terms of functional reserve
      and life expectancy and allows an individualized approach to the elderly. The
      increased susceptibility of the aged to environmental carcinogens has multiple
      causes and provides theoretical support to cancer prevention to the older
      individuals. The natural behavior of cancer may change with age due to intrinsic
      changes in the tumor cells as well as in the tumor host and may lead to both
      increased and decreased aggressiveness of the neoplasm. In the case of breast
      cancer, age seems associated with a more indolent tumor. Cancer screening seems
      effective in older patients with a life-expectancy of 5 or more years. Treatment
      of cancer with chemotherapy may be associated with increased risk of
      complications, especially mucositis and neutropenia. The latter may be
      ameliorated by prophylactic use of growth factors and correction of anemia.

PMID- 12791421
TI  - The role of pineal gland in breast cancer development.
AB  - The role of the modulation of the pineal gland function in development of breast
      cancer is discussed in this review. An inhibition of the pineal function with
      pinealectomy or with the exposure to the constant light regimen stimulates
      mammary carcinogenesis, whereas the light deprivation inhibits the
      carcinogenesis. Epidemiological observations on increased risk of breast cancer
      in night shift workers, flight attendants, radio and telegraph operators and on
      decreased risk in blind women are in accordance with the results of experiments
      in rodents. Treatment with pineal indole hormone melatonin inhibits mammary
      carcinogenesis in pinealectomized rats, in animals kept at the standard
      light/dark regimen (LD) or at the constant illumination (LL) regimen. Pineal
      peptide preparation Epithalamin and synthetic tetrapeptide Epitalon (Ala-Glu-Asp
      Gly) are potent inhibitors of mammary carcinogenesis in rodents and might be
      useful in the prevention of breast cancer in women at risk.

PMID- 12791422
TI  - Mammography screening in elderly women: efficacy and cost-effectiveness.
AB  - The definition of an upper age limit for breast cancer screening is a rather
      complex issue, influenced by several conditions. Randomised trials specifically
      designed to investigate this aspect are not available, but all process indicators
      (positive predictive value, length of sojourn time, sensitivity of the test)
      indicate that screening efficacy does not change with increasing age. On the
      other hand, competing causes of death could decrease screening efficacy beyond
      age 74. Screening benefits depend on life expectancy and people with <5-10 years
      life expectancy are unlikely to benefit from screening, so it is still worthwhile
      considering the variability of life expectancy at different ages. Furthermore,
      economical implications are evident. Public health recommendations need to weigh
      the benefit of screening elderly women against costs, negative side effects and
      potential harm due to overdiagnosis and overtreatment of screen-detected lesions
      expected to have no effect on mortality. In this scenario, the medical system has
      an ethical obligation to properly inform the population invited to screening.
      Over the age of 74 years, encouraging individualized decisions may be more
      appropriate and may indicate further screening for those subjects for whom the
      potential benefit outweighs the potential negative effects.

PMID- 12791423
TI  - Treatment of older breast cancer patients with high recurrence risk.
AB  - Adjuvant treatment of elderly women affected by breast cancer who have a high
      risk of recurrence is one of the most questionable issues in clinical oncology.
      The use of tamoxifen in women with hormone receptor-positive tumors is a
      relatively simple therapeutic option considering the favourable toxicity profile,
      whereas the administration of adjuvant chemotherapy is more complicated and a
      variety of aspects need to be considered. The estimated life expectancy, the
      presence and degree of comorbid conditions, the geriatric assessment and
      estimated benefit from treatment should be taken into account. Due to the lack of
      data from clinical trials in women over the age of 70, the approach is still
      experimental. Clinical trials evaluating the role of adjuvant chemotherapy in
      high risk patients are currently being developed and hopefully in the near
      future, more convincing data on the best drugs, regimens and benefits for the
      treatment of elderly breast cancer patients will become available.

PMID- 12791424
TI  - Prevention and therapy of neutropenia in elderly patients.
AB  - Standard chemotherapy in elderly patients is still nowadays a difficult issue,
      due to the fact that marrow reserve decrease with age and the results might lead
      to higher toxicity of otherwise well tolerated regimen and schedule. In the
      literature, very few data exist of myelosuppression in patients with solid
      tumors, while more data have been published on non-Hodgkin's lymphoma. The burden
      of toxicity increase with age, leading to the fact that some patients with
      curable or sensitive disease do not receive appropriate treatment. One of the
      ways to try to circumvent neutropenia is the prophylactic use of haematopoietic
      growth factors with the double aim of maintaining dose-intensity and reducing
      toxicity. This paper will describe the patterns of marrow toxicity in treating
      elderly patients with cancer and the role of haematopoietic growth factors.

PMID- 12791425
TI  - Estimating the costs of caring for the older breast cancer patient.
AB  - As the population ages, it is expected that more and more elderly women will be
      diagnosed with breast cancer. Relatively little is known about the cost of caring
      for this group of patients. The goals of this article will be to introduce the
      relevant types of costs, to review the available data on these costs and to
      conclude with some thoughts regarding areas for future research.

PMID- 12791426
TI  - Biomarkers and their use in cervical cancer chemoprevention.
AB  - Cervical cancer chemoprevention agents under study include diet and
      micronutrients (particularly beta-carotene, folate, and vitamins A, C, and E);
      medications such as retinoids (retinyl acetate gel, all-trans-retinoic acid, and
      4-hydroxyphenylretinamide) that are chemically related to micronutrients; and
      other chemopreventives meant to affect the carcinogenic process at the cellular
      level, including such polyamine synthesis inhibitors as alpha
      difluoromethylornithine. Agents become reasonable candidates for study when they
      have a biologic rationale, they are of low toxicity, and they can be taken for a
      long period of time. Since the human papillomavirus (HPV) is the major etiologic
      agent, the medication should show activity against HPV-positive preinvasive and
      invasive cell lines. The medication needs to be of low toxicity because it may be
      taken for long periods of time and less toxicity is tolerated in the precancerous
      setting. Until 1995, none of the studies used surrogate end point biomarkers
      (SEBs), relying instead on histologic and colposcopic regression as end points.
      All studies typically included subjects with cervical intraepithelial neoplasia.
      Conclusions to be drawn from these studies include the following: Though
      micronutrients are logical candidates for chemoprevention, they haven't worked
      consistently, and the reasons remain unclear. Furthermore, SEBs need to be
      validated in phase I trials. Finally, a better understanding of the role of HPV
      needs elucidation, including an understanding of the relationship of the
      medication to HPV status and of the immunobiology of HPV throughout the trial.

PMID- 12791427
TI  - Staging of primary cervical cancers: the role of nuclear medicine.
AB  - In nuclear medicine, [18F]-fluorodeoxyglucose positron emission tomography (18FDG
      PET) and lymphatic mapping and sentinel lymphadenectomy (LM/SL) may significantly
      improve the staging of primary cervical cancers. Indeed, the disease progresses
      in a 'level by level' fashion to regional nodes through the lymphatic channels,
      and also to extra-nodal sites via the hematogenous stream. Additionally, the sub
      optimal efficacy of routine radiological protocols, while new combined therapies
      are proving to be more efficient, stresses the need for alternative staging
      procedures. Current data suggest that LM/SL accurately reflects the regional
      lymph node status in early stage cervical cancers, and thus could avoid
      unnecessary complete lymphadenectomies. Also, whole body 18FDG PET may provide
      valuable insights on extra-pelvic and distant tumor spreading, with a significant
      impact on treatment choices. If these promising results are confirmed on large
      controlled trials, LM/SL and 18FDG PET imaging could be incorporated in the
      routine staging work-up of primary cervical cancers.

PMID- 12791428
TI  - Transcatheter arterial procedures in the treatment of patients with
      hepatocellular carcinoma: a review of literature.
AB  - BACKGROUND: Transcatheter arterial procedures (TAP) have been widely used to
      treat hepatocellular carcinoma (HCC) in several clinical settings (advanced and
      neoadjuvant), and contraindications and secondary effects have been clearly
      described. However, it is still unclear which patients should be selected for
      treatment, which procedures should be used, in particular whether or not to add
      an antiblastic agent to embolization, and if the treatment provides a survival
      advantage in patient with HCC. METHODS: We conducted a Medline search for all
      study reports published until May 2002. Data from randomised studies were
      evaluated in detail. RESULTS: Data on the use of TAP for the treatment of
      unresectable HCC mainly come from retrospective studies that are difficult to
      compare because of the lack of standardized procedures. Some prognostic systems
      have been proposed in order to improve the selection of the patients that can
      benefit from treatment. While the effects in terms of tumour response are clearly
      documented, the results in terms of survival are still unclear. CONCLUSIONS: The
      real impact of TAP on survival remains to be determined in all clinical settings.
      The very few published prospective randomised trials are underpowered and cannot
      provide any definitive conclusions. Thus, there is an urgent need for prospective
      controlled trials in order assess the impact of TAP on survival and to compare
      different procedures.

PMID- 12791429
TI  - Evidence for a monoamine mediated, opioid-independent, antihyperalgesic effect of
      venlafaxine, a non-tricyclic antidepressant, in a neurogenic pain model in rats.

PMID- 12791430
TI  - Nociceptive processing in the human brain of infrequent task-relevant and task
      irrelevant noxious stimuli. A study with event-related potentials evoked by CO2
      laser radiant heat stimuli.
AB  - Laser evoked potentials (LEPs) are nociceptive-related brain responses to
      activation of cutaneous nociceptors by laser radiant heat stimuli. We previously
      showed that LEP amplitude during the P2 period (approximately 400 ms) was
      increased by rare noxious stimuli, inside and outside the focus of spatial
      attention. It was postulated that this effect reflected a P3a response indexing
      an involuntary shift of attention. In the present study, LEPs were recorded in a
      three-stimulus oddball paradigm, commonly used to evoke P3a (or novelty-P3).
      CO(2) laser-induced noxious stimuli were delivered on one hand (80%, frequent).
      Two series of rare stronger-intensity deviant stimuli were randomly intermixed:
      target stimuli (10%) were delivered on the same hand while distractor stimuli
      (10%) were delivered on the other hand. Subjects were instructed to count
      targets. During an additional session, strong stimuli were delivered alone on one
      hand without instruction (100%, no-task stimuli). All stimulus types evoked a
      first positivity around 360 ms (P360). Targets and distractors elicited a late
      positive complex (LPC) around 465-500 ms. Topography of LPC to distractors was
      central and significantly more anterior than that of LPC to targets. Distractor
      LPC corresponds to P3a (or novelty-P3) indexing an involuntary orientation of
      attention toward an unexpected new/deviant event. It suggests that at least an
      early part of the LEP positivity (P360) is independent of P3-activities.

PMID- 12791431
TI  - A longitudinal study of the prevalence and characteristics of pain in the first 5
      years following spinal cord injury.
AB  - A longitudinal cohort study of 100 people with traumatic spinal cord injury (SCI)
      was performed to determine the prevalence and severity of different types of pain
      (musculoskeletal, visceral, neuropathic at-level, neuropathic below-level) at 5
      years following SCI. Prospective data on the characteristics of pain up to 6
      months following injury had been collected previously and allowed comparisons
      between the presence of pain at different time points. In addition, we sought to
      determine the relationship between the presence of pain and physical factors
      related to the injury such as level of lesion, completeness and clinical SCI
      syndrome. We also obtained information regarding mood, global self-rated health
      and the impact of pain on function. Of the 100 subjects in the original cohort,
      73 were available for follow up. When all types of pain were included, 59 of the
      73 subjects (81%) reported the presence of pain. Musculoskeletal pain was the
      most common type of pain experienced and was present in 43 subjects (59%), at
      level neuropathic pain was present in 30 subjects (41%), below-level neuropathic
      pain was present in 25 subjects (34%) and visceral pain was present in four
      subjects (5%). Overall, 58% reported their pain as severe or excruciating and
      those with visceral pain were most likely to rate their pain in these categories.
      There was no relationship between the presence of pain overall and level or
      completeness of lesion, or type of injury. However, tetraplegics were more likely
      to report below-level neuropathic pain. This study prospectively demonstrates the
      differing time courses of different types of pain over the first 5 years
      following SCI. There was a strong correlation between the presence of both types
      of neuropathic pain at 5 years and earlier time points but both visceral pain and
      musculoskeletal pain demonstrated a poor correlation between time points. Chronic
      visceral pain occurs in a small percentage of patients and does not correlate
      with the presence of visceral pain early following injury. Those with neuropathic
      pain early following their injury are likely to continue to experience ongoing
      pain and the pain is likely to be severe. In contrast, chronic musculoskeletal
      pain is more common but less likely to be severe and cannot be predicted by the
      presence of pain in the first 6 months following injury.

PMID- 12791432
TI  - Risk factors for non-specific low back pain in schoolchildren and their parents:
      a population based study.
AB  - A survey of adolescent schoolchildren and their parents through a self
      administered questionnaire was conducted to determine the prevalence of low back
      pain (LBP) in schoolchildren and their parents and to assess its association with
      exposure to known and presumed risk factors. A previously validated, self
      administered questionnaire was used for collecting information on back pain
      history, anthropometric measures, physical and sports activity, academic
      problems, hours of leisure sitting, smoking, and alcohol intake. Schoolchildren
      between the ages of 13 and 15 in schools of the island of Mallorca and their
      parents (n=16,394) took part in the study. The lifetime prevalence of LBP was
      50.9% for boys and 69.3% for girls; point prevalence (7 days) was 17.1% for boys
      and 33% for girls. There was a significant association with LBP and pain in bed
      (OR=13.82, 95% CI: 10.47-18.25, P<0.001), reporting scoliosis (OR=2.87, 95% CI:
      2.45-3.37, P<0.001), reporting difference in leg length (OR=1.26, 95% CI: 1.02
      1.56, P=0.033), practice of any sport more than twice a week (OR=1.23, 95% CI:
      1.09-1.39, P=0.001) and being female (OR=1.11, 95% CI: 1.04-1.19, P=0.001). There
      was no association found between LBP and body mass index, the manner in which
      books were transported, hours of leisure sitting, alcohol intake or cigarette
      smoking. Among parents, the lifetime prevalence of LBP was 78.2% for mothers and
      62.6% for fathers; point prevalence (7 days) was 41% for mothers and 24.3% for
      fathers, and there were significant associations with LBP and pain in bed
      (OR=18.07, 95% CI: 14.72-22.19, P<0.001), report of scoliosis (OR=8.77, 95% CI:
      6.44-11.95, P<0.001), report of difference in leg length (OR=2.21, 95% CI: 1.60
      3.04, P<0.001), being a university graduate (OR=1.89, 95% CI: 1.21-2.98,
      P=0.006), being female (OR=1.49, 95% CI: 1.33-1.67, P<0.001), and swimming
      (OR=1.10, 95% CI: 1.4-1.18, P=0.002). There was no association found between LBP
      and alcohol intake, cigarette smoking or the practice of other sports. Although
      there was a positive association in terms of scoliosis between biological parents
      and their children (P<0.001), there was no association found in familial
      (biological or not) occurrence of LBP. The prevalence of LBP among adolescents in
      southern Europe is similar to northern Europe, it is comparable to that in
      adults, and is associated with several factors. There is a strong association
      between pain in bed or upon rising in both adolescents and adults. Scoliosis, but
      not LBP, appears to be related to heredity. Further longitudinal studies are
      necessary to establish risk factors that are predictive for LBP in adolescents.

PMID- 12791433
TI  - Peripheral and central sites of action for A-85380 in the spinal nerve ligation
      model of neuropathic pain.
AB  - Neuronal nicotinic receptor (NNR) agonists such as ABT 594 have been shown to be
      effective in a wide range of preclinical models of acute and neuropathic pain.
      The present study, using the NNR agonist A-85380, sought to determine if NNR
      agonists are acting via similar or differing mechanisms to induce anti
      nociception and anti-allodynia. A systemic administration of the quaternary NNR
      antagonist chlorisondamine (0.4 micromol/kg, intraperitoneal (i.p.)) did not
      alter A-85380-induced (0.75 micromol/kg, i.p.) anti-nociception in the rat paw
      withdrawal model of acute thermal pain. In contrast, previous studies have
      demonstrated that blockade of central NNRs by prior administration of
      chlorisondamine (10 microg i.c.v.) prevents A-85380 induced anti-nociception
      indicating a predominantly central site of action of NNR agonists in relieving
      acute pain. In the rat spinal nerve ligation model of neuropathic pain, A-85380
      induced a dose-dependent anti-allodynia (0.5-1.0 micromol/kg) that was blocked by
      pretreatment with mecamylamine (1 micromol/kg). Interestingly, unlike acute pain,
      both systemic and central administration of chlorisondamine blocked A-85380
      induced anti-allodynia, an effect that was determined not to be due to a non
      specific effect of chlorisondamine or to chlorisondamine crossing the blood-brain
      barrier. The peripheral site of action was shown not to be the primary receptive
      field, since A-85380 had equally potent anti-allodynic effects when it was
      injected into either the affected or unaffected paw. In contrast, infusion of A
      85380 directly onto the L5 dorsal root ganglion on the affected side resulted in
      a dose-dependent and marked anti-allodynia (10-20 microg) at doses that had no
      effect when injected systemically. This effect was blocked by pretreatment with
      chlorisondamine. Together these data further support the idea that different
      mechanisms underlie different pain states and suggest that the effects of NNR
      agonists in neuropathic pain may be due in part to peripheral actions of the
      compounds.

PMID- 12791434
TI  - Efficacy of the NMDA-receptor antagonist memantine in patients with chronic
      phantom limb pain--results of a randomized double-blinded, placebo-controlled
      trial.
AB  - Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by
      excitatory amino acids at NMDA receptor sites. This study was undertaken to
      deduce if NMDA-receptor antagonists may be effective in patients with chronic
      PLP. Therefore a four week double-blinded, randomized placebo-controlled trial
      was performed to evaluate the efficacy of 30 mg memantine/day, an orally
      administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a
      history of at least 12 months PLP and an average pain of at least 4 on the 11
      point numeric rating scale (NRS) were enrolled. The patients completed a
      standardized questionnaire before the trial. PLP intensity and the level of eight
      complaints were assessed during the trial. Number needed to treat (NNT) was
      calculated based on the average PLP during the 3rd week (steady state). In both
      groups, PLP declined significantly in comparison with the baseline (verum: 5.1
      (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without
      a re-rising of the PLP during the washout period. Mean pain relief was 47% in the
      memantine group (10 patients reported more than 50% relief), 40% in the placebo
      group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a
      significant impact only on the prior PLP intensity, but no treatment effect. Two
      patients have demonstrated long-term pain relief under memantine until now (16
      months). The total number of slight adverse events were comparable in both
      groups, but the overall number of severe events was higher in the memantine group
      (P<0.05). This trial failed to demonstrate a significant clinical benefit of the
      NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher
      dosage is probably not tolerable.

PMID- 12791436
TI  - The impact of post-operative pain on outcomes following hip fracture.
AB  - Untreated pain is a major health care issue and very little is known about the
      treatment of pain and the effect of pain on post-operative outcomes in older
      adults. This study was performed to identify the impact of pain on outcomes
      following hip fracture in older adults. Four hundred and eleven consecutive
      cognitively intact patients admitted with hip fracture to four New York hospitals
      were enrolled in a prospective cohort study. Patients were interviewed daily
      using standardized pain assessments. We used multiple logistic regression and
      ordinary least squares linear regression to examine the association of post
      operative pain on immediate post-operative outcomes (duration of stay, physical
      therapy sessions missed or shortened, ambulation following surgery, and post
      operative complications) and outcomes 6 months following fracture (locomotion,
      mortality, return to the community, residual pain). Patients with higher pain
      scores at rest had significantly longer hospital lengths of stay (P=0.03), were
      significantly more likely to have physical therapy sessions missed or shortened
      (P=0.002), were significantly less likely to be ambulating by post-operative day
      3 (P<0.001), took significantly longer to ambulate past a bedside chair (P=0.01),
      and had significantly lower locomotion scores at 6 months (P=0.02). Pain at rest
      was not significantly associated with post-operative complications, nursing home
      placement, survival at 6 months, or residual pain at 6 months. Post-operative
      pain is associated with increased hospital length of stay, delayed ambulation,
      and long-term functional impairment. Whereas appropriate caution is warranted in
      administering opioid analgesics to older adults, these data suggest that improved
      pain control may decrease length of stay, enhance functional recovery, and
      improve long-term functional outcomes.

PMID- 12791435
TI  - Gonadal steroid hormone modulation of nociception, morphine antinociception and
      reproductive indices in male and female rats.
AB  - The purpose of this study was to examine how gonadal steroid hormones modulate
      basal nociception and morphine antinociception relative to regulating
      reproduction in the adult rat. Male and female Sprague-Dawley rats were either
      gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted
      subcutaneously with capsules containing testosterone (T), estradiol (E2),
      dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2,
      T, or empty (0) capsules immediately after surgery, and vehicle or progesterone
      (P4) injections at 4-day intervals. Basal nociception and morphine
      antinociception were tested 28 days after surgery on 50 degrees C and 54 degrees
      C hotplate tests, and reproductive behavior and physiology were assessed shortly
      thereafter. There were no significant differences in baseline hotplate latencies
      among the male treatment groups, but morphine was significantly more potent in
      sham and GDX+T males than in GDX+0 males. The ability of T to increase morphine's
      potency was approximated by its major metabolites E2 and DHT, given together but
      not alone. Baseline hotplate latencies were higher in sham females tested during
      diestrus than in those tested during estrus. Morphine was significantly more
      potent in sham females tested during proestrus and diestrus than in those tested
      during estrus. Baseline hotplate latencies were significantly higher, and
      morphine was significantly less potent in GDX+E2, GDX+E2/P4 and GDX+T females
      than in GDX+0 females. All group differences in basal nociception and morphine
      antinociception observed on the 50 degrees C hotplate test were smaller and
      generally non-significant on the 54 degrees C hotplate test. Steroid
      manipulations produced the expected changes in reproductive behaviors and steroid
      sensitive organs. These results demonstrate that in adult rats, gonadal steroid
      manipulations, that are physiologically relevant, modulate (1) basal nociception
      in females but not males, and (2) morphine's antinociceptive potency in both
      males and females.

PMID- 12791437
TI  - S+ -flurbiprofen but not 5-HT1 agonists suppress basal and stimulated CGRP and
      PGE2 release from isolated rat dura mater.
AB  - Neurogenic inflammation of the meninges, expressed in plasma extravasation and
      vasodilatation, putatively contributes to certain types of headache. Both, non
      steroidal antiinflammatory drugs (NSAIDs) and serotonin-1 (5-HT1) receptor
      agonists are similarly effective antimigraine drugs but their mechanism of action
      is unclear. The clinical observation that sumatriptan lowered plasma levels of
      calcitonin gene-related peptide (CGRP), found increased during migraine attacks,
      drew attention to a possible inhibition of pro-inflammatory neuropeptide release
      from trigeminal afferents. An isolated preparation of fluid-filled rat skull
      cavities was used to study effects of NSAIDs and 5-HT(1B/D) agonists on the dura
      stimulated by inflammatory mediators (bradykinin, histamine and serotonin, 10(
      5)M each). The release of immunoreactive CGRP (iCGRP) and immunoreactive PGE(2)
      (iPGE(2)) was measured in 5-min samples of superfusates using enzyme
      immunoassays. S(+)-flurbiprofen (10(-6)M) strongly reduced the basal and
      stimulated iCGRP release and abolished iPGE(2) release; R(-)-flurbiprofen showed
      much less effect on iPGE(2) liberation and did not influence iCGRP release. The 5
      HT(1B/D) agonists naratriptan and CP93,129 were ineffective on both iCGRP and
      iPGE(2) release. Inspite of its weak COX blocking effect, R(-)-flurbiprofen is
      reported to exert antinociceptive effects, although it has not been tested in
      migraine. Only the potent COX blocker S(+)-flurbiprofen also suppressed iCGRP
      release while the 5-HT(1B/D) agonists were ineffective. Thus, inhibition of
      meningeal neuropeptide secretion is not a common action principle of the drugs
      that could be essential for their antimigraine effects.

PMID- 12791438
TI  - High dose methadone and ventricular arrhythmias: a report of three cases.
AB  - Three patients who developed torsades de pointes while receiving high dosages of
      oral methadone (>600mg/day) are presented. In all of the cases, drug interactions
      involving methadone and CYP3A4 isoenzyme system were possible. Two cases involve
      some previous cardiac impairment. The potential for toxic doses of methadone to
      cause ventricular arrhythmia is raised by these cases. Until further evidence is
      available it may be prudent to be vigilant for arrhythmias when high dosages of
      methadone (>600mg/day) are used, especially in patients on other drugs that
      interact with the CYP3A4 isoenzyme system, or with conditions that predispose to
      torsades de pointes.

PMID- 12791439
TI  - Anti-epileptic drugs as possible neuroprotectants in cerebral ischemia.
AB  - Many similarities exist between cerebral ischemia and epilepsy regarding brain
      damaging and auto-protective mechanisms that are activated following the
      injurious insult. Therefore, drugs that are effective in minimizing seizure
      induced brain damage may also be useful in minimizing ischemic injury. Use of
      such drugs in stroke victims may have important clinical and financial
      advantages. Therefore, the authors conducted a Medline search of studies
      involving the use of anti-epileptic drugs (AEDs) as possible neuroprotectants and
      summarize the data. Most AEDs have been tested in animal models of focal or
      global ischemia and some were already tested in humans, for a possible
      neuroprotective effect. The existing data is rather scant and insufficient but it
      appears that only drugs that have multiple mechanisms of action seem to have some
      potential in conferring a degree of neuroprotection that could be clinically
      applicable to stroke patients. In conclusion, some of the newer AEDs show promise
      as possible neuroprotectants in the setup of acute ischemic stroke but more
      studies are needed before clinical trials in humans could be undertaken.

PMID- 12791440
TI  - A molecular perspective of human circadian rhythm disorders.
AB  - A large number of physiological variables display 24-h or circadian rhythms.
      Genes dedicated to the generation and regulation of physiological circadian
      rhythms have now been identified in several species, including humans. These
      clock genes are involved in transcriptional regulatory feedback loops. The
      mutation of these genes in animals leads to abnormal rhythms or even to
      arrhythmicity in constant conditions. In this view, and given the similarities
      between the circadian system of humans and rodents, it is expected that mutations
      of clock genes in humans may give rise to health problems, in particular sleep
      and mood disorders. Here we first review the present knowledge of molecular
      mechanisms underlying circadian rhythmicity, and we then revisit human circadian
      rhythm syndromes in light of the molecular data.

PMID- 12791442
TI  - Input and output stations of the entorhinal cortex: superficial vs. deep layers
      or lateral vs. medial divisions?
AB  - Based on the results of recent electrophysiological and anatomical studies, we
      argue that the classical division of the entorhinal cortex (EC) into a
      superficial layer input station and deep layer output station is no longer
      tenable. We point out that the anatomical data suggest that the medial and
      lateral divisions of EC are separate, and recent studies of the propagation of
      signals originating in the lateral olfactory tract and perirhinal cortex to the
      EC [J. Neurophysiol. 83 (2000) 1924-1931; Biella and de Curtis, 2000) indicate
      that the lateral division is the input station, and the medial division the
      output station for information processed in the hippocampus and subiculum.

PMID- 12791441
TI  - Molecular anatomy of intercellular junctions in brain endothelial and epithelial
      barriers: electron microscopist's view.
AB  - In this review, we have tried to summarize the current knowledge on the
      distribution of important molecular components of intercellular junctions-both
      tight junctions (TJs) and adherens junctions (AJs)-at the level of
      ultrastructure. For this purpose, immunogold procedure was applied to ultrathin
      sections of brain samples obtained from mice, rats, and humans and embedded in
      hydrophilic resin Lowicryl K4M. The results of our observations performed with
      transmission electron microscopy (EM) are discussed and compared with findings of
      other authors. Although the main structures responsible for the barrier and fence
      functions of the blood-brain barrier (BBB) and blood-CSF barrier are TJs present
      between endothelial cells (ECs) of brain capillaries and epithelial cells of the
      choroid plexus, their functional characteristics (e.g. tightness of the barrier
      evaluated by electrical resistance) differ significantly. Therefore, our main
      attention is focused on the presence and distribution of both intrinsic, i.e.
      integral membrane (transmembrane), molecules such as occludin, claudins, and
      junctional adhesion molecule (JAM) in TJs, and cadherins in AJs, as well as
      peripheral molecules of both types of junctions, e.g. zonula occludens (ZO)
      proteins and catenins. The latter group of molecules connects transmembrane
      proteins with the cell cytoskeleton. A close spatial association of the TJ
      proteins with those of AJs indicates that both junctional types are intermingled
      in the BBB type of endothelium. One of most important purposes of this work is to
      find out the junction-associated molecules that can serve as sensitive markers of
      normal or disturbed function of brain barriers. Understanding the structural
      functional relations between molecular components of junctional complexes in
      physiological and experimental conditions of both barriers can provide important
      information about the etiology of various pathological conditions of the central
      nervous system and also help to elaborate new therapeutic approaches.

PMID- 12791443
TI  - Watch how to do it! New advances in learning by observation.
AB  - Recent data demonstrate that the cerebellum contributes to the internal
      representation of action. This representation is used not only to generate motor
      actions, but also to understand and learn the actions and skills of others by
      imitation. The cerebellar networks appear to be indispensable for acquiring
      complex behaviors and procedures. The cerebellar role in the acquisition of
      procedural competencies is particularly evident in spatial information
      processing. The cerebellum allows acquiring by observation competencies in
      exploration behaviors as efficient as the competencies acquired by actually
      performing the same task. The specificity of the cerebellar role in the
      acquisition phases of learning by observation is demonstrated by the complete
      absence of spatial learning when the observational training is performed in
      presence of a cerebellar lesion. This datum is further corroborated by the
      evidence that, once acquired, spatial procedures can be efficiently performed
      even in the presence of cerebellar damage, in agreement with the neuroimaging
      findings of low cerebellar activation after prolonged practice. The finding that
      the cerebellum is involved in procedural acquisition and in observational
      learning allowed us to dissect a complex behavior into single behavioral units
      forming a complete procedural sequence, demonstrating that such behavioral units
      do exist and can be independently acquired.

PMID- 12791444
TI  - Is synchronized neuronal gamma activity relevant for selective attention?
AB  - Today, much evidence exists that sensory feature binding is accomplished by phase
      synchronization of induced neuronal gamma activity (30-80 Hz). Recent studies
      furthermore suggest that phase synchronization of induced gamma activity may
      represent a general mechanism enabling transient associations of neural
      assemblies and thus may play a central role in cortical information processing.
      Here, we describe findings indicating that synchronized gamma activity is
      moreover specifically involved in selective attention. While feature binding
      appears to depend primarily on induced gamma synchronization, attentional
      processes seem to involve both induced and evoked gamma oscillations. Yet it is
      still an open question, as to which top-down and bottom-up processes are
      associated with attentional modulation of gamma activity. A possible mechanism to
      project influences from attentional control structures to areas concerned with
      stimulus representation and vice versa, may be neuronal synchronization and the
      resulting firing rate changes of coincidence-detecting neurons in target areas.

PMID- 12791445
TI  - "Auditory neuropathy": physiologic and pathologic evidence calls for more
      diagnostic specificity.
AB  - The term "auditory neuropathy" is being used in a rapidly increasing number of
      papers in the audiology/otolaryngology literature for a variety of individuals
      (mostly children) who fulfill the following criteria: (1) understanding of speech
      worse than predicted from the degree of hearing loss on their behavioral
      audiograms; (2) recordable otoacoustic emissions and/or cochlear microphonic;
      together with (3) absent or atypical auditory brain stem responses. Because of
      the general lack of anatomic foundation for the label "auditory neuropathy" as
      currently used, we review the anatomy of the auditory pathway, the definition of
      neuropathy and its demyelinating, axonal, and mixed variants. We submit that the
      diagnostic term "auditory neuropathy" is anatomically inappropriate unless
      patients have documented evidence for selective involvement of either the spiral
      ganglion cells or their axons, or of the 8th nerve as a whole. In view of
      biologic differences between peripheral nerves and white matter tracts in the
      brain, the term "auditory neuropathy" is inappropriate for pathologies affecting
      the central auditory pathway in the brainstem and brain selectively. Published
      reports of patients with "auditory neuropathy" indicate that they are extremely
      heterogeneous in underlying medical diagnosis, age, severity, test results, and
      that only a small number have undergone the detailed investigations that would
      enable a more precise diagnosis of the locus of their pathologies. The
      electrophysiology of peripheral neuropathies and the deficits expected with
      pathologies affecting the hair cells, spiral ganglion cells and their axons
      (auditory neuropathy sensu stricto), and brain stem relays are reviewed. In order
      to serve patients adequately, including potential candidates for cochlear
      implants, and to increase knowledge of auditory pathologies, we make a plea for
      more comprehensive evaluation of patients who fulfill the currently used
      audiologic criteria for "auditory neuropathy" in an effort to pinpoint the site
      of their pathologies. We suggest that the term auditory neuropathy be limited to
      cases in which the locus of pathology is limited to the spiral ganglion cells,
      their processes, or the 8th nerve, and that the term neural hearing loss be
      considered for pathologies that affect all higher levels of the auditory pathway,
      from the brainstem to the auditory cortex.

PMID- 12791446
TI  - The Internet-current trends and future expectations among Brazilian pediatricians
      and otolaryngologists with a special interest in pediatric otolaryngology.
AB  - OBJECTIVE: To assess Internet use among a group of Brazilian pediatricians and
      otolaryngologists and to inquire about possible Web based medical resources.
      METHODS: Questionnaires were distributed among attendees of a 2001 Pediatric
      Otolaryngology meeting in Brazil. Multiple choice or yes/no questions related to
      the use of the Internet among physicians were presented. RESULTS: All of the 99
      respondents of an estimated 900 attendees, had Internet access (high-speed 18%,
      conventional 77%); 52% at home, 42% in the office and 6% at both sites. Eighty
      one percent of those responding regularly used the Internet for medical updating.
      Sharing a pediatric otolayngology medical association Web site with patients was
      desired by 73%; an interest in personal Web based medical information and updates
      was demonstrated by 97%. Five percent of respondents already had established
      personal practice Web sites and 54% agreed with potential benefits for improving
      medical practice. CONCLUSION: The potential role of electronic communication and
      a desire to establish a pediatric otolaryngology Web site that would maximize
      inclusiveness is appreciated by this group of Brazilian otolaryngologists and
      pediatricians.

PMID- 12791447
TI  - Atrial natriuretic peptide levels in children with habitual epistaxis.
AB  - OBJECTIVE: By virtue of no identifiable causes in the majority of children with
      habitual epistaxis, it continues to be problematic in pediatric clinical
      practice. The purpose of this study is to explore the possible change of atrial
      natriuretic peptide (ANP) levels in the children with epistaxis. METHODS: Both
      the plasma and nasal mucus ANP levels have been determined in 30 sick children by
      a sensitive radioimmunoassay (RIA) technique. RESULTS: Our results revealed that
      the plasma and nasal mucus ANP levels were considerably decreased in 24 children
      with habitual epistaxis when compared with control group (P<0.05), making up 80%,
      and amongst the interest of these are the nasal mucus ANP levels changing
      inversely as the times bled from the nose. CONCLUSION: Although the plasma and
      nasal mucus ANP levels will not establish the diagnosis of its etiology, it is
      helpful for us to know the cardiovascular status compensating for chronic blood
      loss in the children with habitual epistaxis.

PMID- 12791448
TI  - The effects of dexamethasone, bupivacaine and topical lidocaine spray on pain
      after tonsillectomy.
AB  - OBJECTIVE: To compare the administration of bupivacaine hydrochloride,
      dexamethasone and lidocaine hydrochloride in decreasing post-tonsillectomy pain.
      METHODS: Eighty patients were enrolled in the study in ENT Clinic, Firat
      University, and in ENT Clinic Elazig SSK Hospital, Elazig (Turkey). Children
      between 6 and 14 years of age referred to our department for bilateral
      tonsillectomy for either recurrent tonsillitis or tonsillar hypertrophy. Data
      from 80 patients were analyzed. The first group had bupivacaine hydrochloride.
      The second group had dexamethasone infiltrated around each tonsil. The third
      group was given equal doses of 10% lidocain hydrochloride sprayed on the
      tonsillectomy fossa four times a day, and a placebo group received 9% NaCl
      applied to the tonsillar fossa four times a day. Pain scores, determined by
      visual analog scale, were obtained in the first, third and seventh postoperative
      days. RESULTS: Pain scores in the postoperative period were identical in the
      first, third and seventh postoperative days. According to VAS results the groups
      were compared on the basis of postoperative pain. In the first postoperative day,
      the difference between bupivacaine-placebo, dexamethasone-placebo and lidocaine
      placebo groups was found to be statistically significant (P<0.05). Nevertheless
      the difference between bupivacaine-dexamethasone, bupivacaine-lidocaine and
      dexamethasone-lidocaine were not significant (P>0.05). In the third postoperative
      day, the difference between bupivacaine and lidocaine group found to be
      statistically significant (P<0.05). In the seventh post-operative day the results
      of bupivacaine, dexamethasone, lidocaine and placebo groups were similar
      (P>0.05). CONCLUSION: Bupivacaine, Dexamethasone and Lidocaine nasal aerosol
      decreased the pain significantly in the first postoperative day when it was
      compared with the placebo group. These three medicines can be used to reduce pain
      for children during the postoperative period applied tonsillectomy during the
      post-operative period. But lidocaine was more preferable, reducing pain in the
      third postop day better than bupivacaine.

PMID- 12791449
TI  - The perceived risk of variant Creutzfeld-Jakob disease and the effect of
      additional delay in tonsillectomy: a questionnaire based parents perspective.
AB  - OBJECTIVES: In February 2001 the United Kingdom Department of Health in
      conjunction with the British Association of Otolaryngology, Head and Neck
      Surgeons decreed that all non-emergency tonsillectomies should be performed using
      disposable instruments because of the theoretical risk of transmission of variant
      Creutzfeld-Jakob disease (vCJD). There was an understandable delay in the
      provision of these instruments by the various manufacturers, leading to an
      increase in waiting time for surgery. It was decided to assess parental attitudes
      to the risk of vCJD, and assess the effect the additional delay had on their
      child. METHOD: A questionnaire was sent to the parents of all 249 children on the
      waiting list for tonsillectomy. RESULTS: Seventy percent replied, and of these,
      37% felt there was a risk of reusing instruments, only 10% felt there was no
      risk, and the remaining 53% did not know if there was any risk. Nevertheless 41%
      of parents would have gone ahead using old instruments if allowed. All parents of
      the 73 children waiting greater than 6 months were questioned on the effect of
      the additional delay. Only 7% reported improvement in symptoms, and 68% felt the
      additional delay had badly affected their child's health and wellbeing. Ninety
      percent of parents felt their child's symptoms still warranted tonsillectomy.
      CONCLUSION: There is an awareness of risk of vCJD among parents whose children
      await tonsillectomy, although understandably the level of risk they feel is hard
      to quantify. The rate of symptom resolution whilst on the waiting list was very
      low.

PMID- 12791450
TI  - Development and characterization of a pooled Haemophilus influenzae genomic
      library for the evaluation of gene expression changes associated with mucosal
      biofilm formation in otitis media.
AB  - Haemophilus influenzae is one of the most important respiratory pathogens of man.
      It has been etiologically associated with otitis media, otorrhea, and chronic
      obstructive pulmonary disease. Identification of new genomic elements will
      provide novel targets to fight chronic infections caused by this organism.
      OBJECTIVE: The new paradigm that chronic infections are caused by bacterial
      biofilms prompted us to study the relationship between bacterial pathogenicity,
      biofilm formation and bacterial communal cooperation. To do this, it is essential
      to determine the virulence gene sets that are involved in the above processes and
      whether they are present in every bacterial cell or distributed in a "communal
      gene-pool", the distributed genome hypothesis (DGH). We designed, constructed and
      characterized a highly redundant genomic DNA library comprised of the genomes of
      ten low passage clinical isolates of H. influenzae carrying large numbers of
      genes that are not present in the laboratory strains of H. influenzae. METHODS:
      Genomic DNA fragments of the ten clinical strains were hydro-dynamically sheared
      to produce a mean fragment size of 1.5-2.5 kb. The ten sheared DNAs were than
      pooled and used in the construction of a genomic library with 76800 clones.
      RESULTS: Our restriction endonuclease and sequence analyses of 800 clones
      demonstrate that 75% of the clones carry an insert larger than 0.5 kb. The
      library has an approximately 1.5 kb average insert size, and therefore, better
      than 4.5x redundancy for each of the genomes of the ten clinical isolates. Our
      sequencing effort ( approximately 1 million nucleotides to date) reveals that a
      high percentage of genes (75 clones, 11% of the 686 sequenced clones) present in
      this library are not represented in the genome of the reference strain H.
      influenzae Rd. CONCLUSIONS: The library, based on the above results, has a better
      than 4.5x coverage for each of the ten constituent genomes. On the basis of our
      preliminary sequencing data ( approximately 1 million nucleotides) the library
      lacks of highly repeated sequences, therefore, the expected genome coverage
      (4.5x) is not degraded. Using the prevalence of non-Rd like sequences (11%)
      detected during characterization of the genomic library, we estimated that the
      library contains DNA sequences equivalent to approximately 2 million bp, which
      are not represented in the reference genome of the H. influenzae Rd strain and
      that is greater in size than the genome of this reference strain, providing ample
      targets for innovative drug design.

PMID- 12791451
TI  - Clinical significance of incidental magnetic resonance image abnormalities in
      mastoid cavity and middle ear in children.
AB  - OBJECTIVE: Magnetic resonance imaging of the head may reveal incidental findings
      in paranasal sinuses. The purpose of this study was to discover whether similar
      changes could be identified in the mastoid cavity and middle ear as well.
      METHODS: A group of 50 children undergoing magnetic resonance imaging of the head
      for suspected intracranial pathology were prospectively gathered. Their parents
      completed a questionnaire concerning each child's medical history connected with
      acute otitis media. Otoradiologists evaluated the pictures for mastoid cavity and
      middle ear and paranasal sinus abnormalities. RESULTS: In six (12%) children,
      magnetic resonance imaging detected abnormalities resembling acute inflammatory
      changes, although none had had acute otitis media during the preceding last 3
      months. Abnormalities detected in the paranasal sinuses were not correlated with
      abnormalities in the mastoid cavity and middle ear. CONCLUSIONS: High signal
      intensity in magnetic resonance images from the mastoid cavity and middle ear may
      be incidental and without any clinical significance. These findings must be
      interpreted together with knowledge of the child's medical condition and clinical
      examination of the ears.

PMID- 12791452
TI  - Muscular, functional and orthodontic changes in pre school children with enlarged
      adenoids and tonsils.
AB  - INTRODUCTION: Hypertrophy of the adenoids and palatine tonsils is the second most
      frequent cause of upper respiratory obstruction and, consequently, mouth
      breathing in children. Prolonged mouth breathing leads to muscular and postural
      alterations which, in turn, cause dentoskeletal changes. OBJECTIVE: The aim of
      this study was to determine muscular, functional and dentoskeletal alterations in
      children aged 3-6 years. MATERIALS AND METHODS: Seventy-three children, including
      44 with tonsil hypertrophy and 29 controls, were submitted to
      otorhinolaryngologic, speech pathologic and orthodontic assessment. RESULTS:
      Otorhinolaryngologic evaluation revealed a higher incidence of nasal obstruction,
      snoring, mouth breathing, apneas, nocturnal hypersalivation, itchy nose, repeated
      tonsillitis and bruxism in children with tonsils hypertrophy. Speech pathologic
      assessment showed a higher incidence of open lip and lower tongue position, and
      of hypotonia of the upper and lower lips, tongue and buccinator muscle in these
      children, accompanied by important impairment in mastication and deglutition.
      Orthodontic evaluation demonstrated a higher incidence of lower mandible position
      in relation to the cranial base, a reduction in lower posterior facial height,
      transverse atresia of the palate, and a dolicofacial pattern. CONCLUSION:
      Postural and functional alterations anticipate dentoskeletal changes, except for
      the facial pattern. Postural alterations and the skeletal pattern seem to play an
      important role in infant dentofacial growth.

PMID- 12791453
TI  - Day-case paediatric mastoid surgery.
AB  - OBJECTIVE: Children have traditionally been kept in hospital overnight after
      mastoid surgery, but evidence from the US in adults suggests that a substantial
      number of patients may be suitable for discharge on the day of surgery. We sought
      to ascertain the proportion of our children having mastoid operations between
      February 1994 and December 2000 who were suitable for same-day discharge. We also
      evaluated some of the factors that prevented discharge the same day. METHODS: A
      standard proforma was used to record relevant data in 35 children (mean age 10
      years 6 months) undergoing consecutive mastoid operations at Mayday University
      Hospital, London, UK. Operative findings, duration of anaesthesia and time back
      on ward were recorded as well as details regarding admission, follow-up findings
      and complications. A bed was booked preoperatively but there was intent to
      discharge the patient if feasible. RESULTS: Nine out of twelve patients (75%)
      operated between 1998 and 2000 were suitable for discharge on the day of surgery.
      The pre-1998 discharge rate was 20%. Only one of the former group of patients
      underwent a modified radical mastoidectomy in comparison with ten such procedures
      pre-1998. There was a significant relationship between extent of surgery and in
      patient admission. The outcomes of day-case mastoid surgery, in terms of
      complications rates and overall success rates, were comparable with surgery
      performed on an in-patient basis. Using correlation analysis, no relationship
      could be found between duration of anaesthesia and time of arrival back on the
      ward and in-patient admission. CONCLUSION: Children can undergo mastoid
      procedures safely and effectively on a day-case basis but should still have a bed
      booked pre-operatively as the majority will require admission. The main factor
      related to admission was the mastoid procedure performed. With improvements in
      surgical and anaesthetic techniques and other advances, operations such as
      atticotomy may become standard day-case procedures in paediatric patients.

PMID- 12791454
TI  - Day-case tonsillectomy in children: parental attitudes and consultation rates.
AB  - OBJECTIVE: In Europe, the day-case tonsillectomy rate in children is slowly
      increasing, but whether parents really want this rapid discharge of their child
      is questionable. The fear is that aftercare might fall solely on community care.
      The aim of this prospective study was to introduce pediatric day-case
      tonsillectomy to our hospital and to determine parents' attitudes to this
      procedure. The other interest centered on consultation rates within the 2-week
      recovery period. METHODS: One hundred children aged 3-16 years had day-case
      tonsillectomy (38) or adenotonsillectomy (62). Peri-operative and post-operative
      complications were recorded. Parents were phoned the next day and 1-4 months
      after the operation. Parents' opinions of day-case surgery and consultations with
      healthcare professionals during the 2-week recovery period were recorded.
      RESULTS: Ninety children went home the day of the operation. Vomiting was the
      most frequent complication. No primary hemorrhages occurred. Called the next day,
      100% of parents felt that their children were better served spending their first
      night at home as compared with staying in hospital. Called 1-4 months later,
      94.5% of parents still thought this way. In the 2-week recovery period following
      the tonsillectomy, 13% of patients visited a physician and 17% called for
      information. These numbers include patients with secondary hemorrhage. If these
      are excluded, 5% of patients visited a physician and 13% called for advice.
      Children were taken back to hospital only due to secondary hemorrhage.
      CONCLUSIONS: Most parents considered day-case tonsillectomy to be suitable for
      their family. Consultation rates were low. Careful patient selection and adequate
      pre-operative information are prerequisites for day-case tonsillectomy.

PMID- 12791455
TI  - Incidence and outcome of middle ear disease in cleft lip and/or cleft palate.
AB  - OBJECTIVE: Otitis media with effusion is known to be very common among children
      with cleft palate, however, less is known regarding the natural history and
      outcome in this group. The purpose of the present study was to examine the
      incidence, natural history, treatment, and outcome of middle ear disease in
      children with clefts. METHODS: A questionnaire was sent to the parents of all
      children registered on the cleft lip and palate database at our institution. The
      medical records of all respondents were also reviewed. Statistical analysis of
      the results was performed using Fisher's exact test in contingency tables and
      binary logistic regression analyses, where appropriate. RESULTS: 397 fully
      completed questionnaires were returned. Ear disease was much more common in
      children with cleft palate, or cleft lip and palate, than in children with cleft
      lip. Among children with cleft palate, ear problems (infections and/or hearing
      loss) were most prevalent in the 4-6-year-old age group. However, ear problems
      persisted at a substantial level for many years after this; only after the age of
      12 years did problems appear to settle. The incidence of below normal current
      hearing and of surgery for chronic otitis media was significantly related to
      history of ear infections (P=0.000 and 0.000, respectively), and to increased
      number of ventilation tube insertions (P=0.000 and 0.000, respectively).
      CONCLUSIONS: Middle ear disease is common in children with cleft palate, and,
      unlike the case for children without clefts, has a prolonged recovery, and a
      substantial incidence of late sequelae. The higher incidence of below normal
      hearing and surgery for chronic otitis media in children undergoing a greater
      number of ventilation tube insertions, although most likely reflecting an
      increased underlying severity of otitis media in these children, also underlines
      the lack of long-term benefits of ventilation tubes in this group.

PMID- 12791456
TI  - Sclerotherapy for lymphangioma in children.
AB  - Although surgical excision has been considered to be the treatment of choice by
      most of the surgeons, sclerotherapy of lymphangioma has gained popularity during
      recent years. A prospective clinical trial was conducted to evaluate the efficacy
      of bleomycin and OK-432 sclerotherapies for treating lymphangioma in children.
      Fifteen patients were enrolled in the study conducted between 1998 and 2002. All
      patients were hospitalized. Bleomycin or OK-432 was injected into the lesion.
      Patients were observed in the hospital for 1 day. The response was considered as
      excellent in cases with total disappearance of the lesion. If the lesion was
      regressed more than 50% of the original size, the response was considered as
      good. Little or no change in the size of lesion was considered to be a poor
      response. Ten girls and five boys with ages ranging from 4 days to 12 years were
      treated. Five patients had been operated previously for lymphangioma. Most of the
      lesions were located only in the cervical region (n=13). Other cases revealed
      extensions into the mediastinum (n=1) or axilla (n=1). Bleomycin (n=8, 2.87+/
      2.03 inj.), OK-432 (n=5, 2+/-1 inj.) or both in order (n=2, 6 and 16 injs.) were
      injected. No allergic reaction, scar formation or pulmonary complication was
      encountered. Fever (11%), local reactions (4%) and vomiting (2%) were encountered
      following a total of 55 injections. After a follow-up period of 6-36 months, the
      responses were excellent in 53.4%, good in 26.7% and poor in 6.6%. Macrocysts
      disappeared in the remaining 13.3% of patients who had mixed cervicofascial
      lymphangioma. Lower success rates were encountered among patients who had
      undergone prior surgery. Sclerotherapy with bleomycin and OK-432 is effective in
      the treatment of lymphangioma in children. Adverse effects are minor and rarely
      encountered. However, the surgeon should be alert for the possible serious
      complications. Sclerotherapy can be also used as an adjunctive therapy in the
      treatment plan of widespread or mixed forms of lymphangiomas. In the light of our
      results, sclerotherapy should be preferred as the primary mode of treatment in
      childhood lymphangiomas.

PMID- 12791458
TI  - Improving children's cooperation with tracheotomy care by performing and caring
      for a tracheotomy in the child's doll-a case analysis.
AB  - Described is a 2-year-old child who required a tracheotomy for an obstructing
      laryngeal tumor. Post-operatively the child responded with extreme anxiety and
      refused to cooperate with tracheostomy care including suctioning, tie changing
      and cannula change. A novel approach was attempted. We performed a tracheotomy on
      the child's favorite doll and taught her to perform all the necessary
      tracheostomy care on the doll. Once the child became accustomed to treating the
      doll, it became much easier to care for her tracheostomy and compliance to
      treatment improved greatly to the point were restraint was no longer required.
      This model of mock surgery and care of a child's doll may be helpful in treating
      young children with tracheotomies.

PMID- 12791457
TI  - Role of respiratory viruses in children with acute otitis media.
AB  - OBJECTIVE: The role of viral infection in acute otitis media (AOM) has not been
      fully elucidated. We determined the presence of various respiratory viruses in
      middle ear fluid (MEF) specimens from children with AOM in order to determine
      whether viral infection or combined effects of viral and bacterial infection
      enhance or prolong the inflammation in the middle ear, thus worsening clinical
      outcome. METHODS: Multiplex nested reverse transcription-polymerase chain
      reactions was carried out to detect influenza A and B viruses, respiratory
      syncytial virus (RSV) types A and B, parainfluenza virus types 1, 2, and 3;
      rhinovirus; and adenovirus in 93 MEF specimens from 79 children with AOM. And we
      examined whether viral infection with or without an identifiable bacterial
      infection affect clinical outcomes in AOM. We considered persistent MEF (fluid
      accumulation in the middle ear persisting up to 1 month after treatment), early
      recurrence of AOM (within 1 month after initial improvement), and recurrent AOM
      (more than three recurrences during 6 months of follow up) as indicators for
      evaluating clinical outcomes. RESULTS: One or more respiratory viruses were
      detected in 39 specimens (42%); a total of 42 viral infections identified (three
      specimens were infected by two viruses). Of the 42 infections, RSV type A was
      detected in 29, adenovirus in eight, rhinovirus in three, and influenza virus in
      two. RSV accounted for 73% of viral detections. In children younger than 2 years,
      RSV infection combined with Streptococcus pneumoniae or Hemophilus influenzae
      infection carried a higher risk for persistent middle ear effusion than infection
      with RSV infection alone or those bacterial infection alone. CONCLUSIONS:
      Accordingly, vaccination of young children against RSV as well as S. pneumoniae
      and H. influenzae is important in improving the prognosis in AOM.

PMID- 12791459
TI  - First branchial cleft sinus presenting with cholesteatoma and external auditory
      canal atresia.
AB  - First branchial cleft abnormalities are rare. They may involve the external
      auditory canal and middle ear. We describe a 6-year-old girl with congenital
      external auditory canal atresia, microtia, and cholesteatoma of mastoid and
      middle ear in addition to the first branchial cleft abnormalities. Clinical
      features of the patient are briefly described and the embryological relationship
      between first branchial cleft anomaly and external auditory canal atresia is
      discussed. The surgical management of these lesions may be performed, both the
      complete excision of the sinus and reconstructive otologic surgery.

PMID- 12791460
TI  - Streptococcus acidominimus infection in a child causing Gradenigo syndrome.
AB  - Gradenigo syndrome is a rare presentation of acute petrositis. The clinical triad
      of Gradenigo syndrome consists of acute suppurative otitis media, severe
      unilateral headache and abducens nerve palsy. We report the first case of
      Gradenigo syndrome caused by Streptococcus acidominimus, a Gram-positive coccus
      of the Streptococcus viridans group, which rarely causes deep-seated infection in
      humans. CONCLUSION: Gradenigo syndrome may complicate acute otitis media and
      should be suspected in case of unilateral headache and abducens nerve palsy.
      Conservative medical treatment without surgery may be considered in some
      patients.

PMID- 12791461
TI  - Laryngeal sporotrichosis causing stridor in a young child.
AB  - Fungal infections of the larynx are rare entities that must be considered in the
      differential diagnosis of the patient who presents with laryngeal symptoms. We
      present an unusual case of initially recurrent and then persistent stridor in a
      19-month-old girl, unresponsive to 4 months of antibiotic and steroid therapy.
      Upon our laryngoscopic examination, the patient was noted to have an ulcerated,
      granulomatous process involving the larynx. She also had an erythematous papule
      on the left thigh. Fungal cultures of both sites grew Sporothrix schenckii. The
      patient was treated with systemic antifungal medications and had complete
      resolution of her symptoms. We discuss the pathophysiology and possible source of
      this unusual form of sporotrichosis, the first such case reported in a child. We
      emphasize the role of empiric steroid therapy in exacerbating and eventually
      enabling dissemination of the infection. We also review the manifestations of
      sporotrichosis infections of the head and neck. This case demonstrates the vital
      importance of careful diagnosis and proper treatment of stridor in children.

PMID- 12791462
TI  - Resistant Haemophilus influenzae in community-acquired respiratory tract
      infections: a role for cefixime.
AB  - An increase in Haemophilus influenzae resistance has been documented around the
      world during the last 30 years. Resistance is due to the production of beta
      lactamases, and/or changes to penicillin-binding protein (PBP) targets. The
      resistance problem has led to the need for new therapeutic strategies aimed at
      maintaining effective management of both upper respiratory tract infections
      (URTIs) and lower respiratory tract infections (LRTIs). Among antimicrobial
      agents tested, third-generation cephalosporins have been shown to possess
      excellent in vitro activity against beta-lactamase-positive and -negative
      isolates, corresponding with proven clinical efficacy in a wide range of RTIs.
      The role of H. influenzae in RTIs is outlined, changing trends in epidemiological
      surveillance studies monitored and implications for therapy, based upon results
      of clinical trials discussed.

PMID- 12791463
TI  - Local treatment of viral disease using photodynamic therapy.
AB  - Although reports of the photodynamic inactivation of viruses appeared in 1928,
      long before chemotherapeutic antiviral drugs, the first clinical trial in humans
      the topical treatment of herpes genitalis-did not take place until the early
      1970s. Trials were discontinued due to the transformation of healthy cells and
      concomitant incidence of Bowen's disease in some patients, probably due to the
      migration of infective sections of photodamaged viral nucleic acid. With the
      modern development of photodynamic therapy as a cancer treatment and the use of
      photosensitisers in the photodecontamination of blood products, a great deal of
      experience has been gained, both in the minimisation of side effects in humans
      and in the targeting and eradication of viruses. This suggests that the
      photodynamic approach to a range of virus-associated infections, lesions and
      cancer might now be revisited with greater success.

PMID- 12791464
TI  - Vancomycin for Staphylococcus aureus therapy of respiratory tract infections: the
      end of an era?

PMID- 12791465
TI  - Analysis of parameters and validation of method for normalized interpretation of
      antimicrobial resistance.
AB  - The method of normalized resistance interpretation (NRI), uses the high-zone side
      of the susceptible peak in a zone diameter histogram as an internal calibrator to
      construct the real standard distribution of susceptible isolates even in the
      presence of resistant isolates. NRI parameters were optimized using control
      strain histograms from microbiology laboratories in Stockholm, Argentina, and the
      Philippines. A moving average based on four-zone values was slightly better than
      based on two-zone average values. The optimal peak adjustment from the switch
      position of the moving average was 1.0 for two-zone averages and 2.5 for four
      zone averages. A comparison between true means and NRI-calculated means showed a
      highly significant correlation (R(2)=0.963). Coefficients of variation (CV),
      comparing the CV of the true distribution of control strain test results with the
      NRI calculated distribution, identified two types of aberrant histograms. NRI
      calculations on clinical isolates of Escherichia coli and Staphylococcus aureus
      from selected laboratories showed a good agreement between the local resistance
      interpretations with the NRI calculated levels. One type of deviation was most
      marked with cephalothin histograms for E. coli isolates where the regular zone
      breakpoints used cut through the population of susceptible strains. With proper
      markers for required quality of disc test results, the NRI method might be a
      valuable tool for both resistance surveillance and for quality control of the
      disc diffusion method.

PMID- 12791466
TI  - Distribution of tetracycline resistance genes tet(M), tet(O), tet(L) and tet(K)
      in blood isolates of viridans group streptococci harbouring erm(B) and mef(A)
      genes. Susceptibility to quinupristin/dalfopristin and linezolid.
AB  - Susceptibility to erythromycin, tetracycline, clindamycin,
      quinupristin/dalfopristin and linezolid was investigated using 111 consecutive
      non-duplicate blood culture isolates of viridans-group streptococci (VGS). The
      erm(B) and mef(A) genes were detected, either alone or in combination, in the 47
      (42%) erythromycin-resistant strains. The tet(M) gene alone was predominant (78%)
      in the 36 (35%) tetracycline-resistant isolates. Two isolates carried the tet(O)
      gene alone and two others the tet(L) associated with tet(O) or tet(M). The
      association between erythromycin and tetracycline resistance was common and the
      erm(B) and tet(M) determinants seem to be associated in our VGS. We found three
      isolates resistant to quinupristin/dalfopristin, all of them were erythromycin
      and tetracycline-resistant. For all isolates tested, linezolid MICs were <or=2
      mg/l.

PMID- 12791467
TI  - Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in a
      Greek tertiary care hospital, over an 8-year-period.
AB  - A total of 1019 non-replicate, consecutively isolated methicillin-resistant
      Staphylococcus aureus (MRSA) strains were collected from in-patients of a
      tertiary care general hospital in Athens, Greece, during the period 1994-2001.
      The susceptibility, resistance phenotypes and the dissemination of these isolates
      among hospital wards were studied. Total MRSA and gentamicin-resistant MRSA, as a
      proportion of the S. aureus isolates, increased from 33 and 9% in 1994 to 50.1
      and 33.3% in 2001, respectively. Three main multi-resistant phenotypes
      predominated, representing 50.9% of the total MRSA isolates in 2001. MRSA strains
      susceptible to all antibiotics tested decreased to 1.9% in 1997 and again
      increased to 13.5% in 2001. A gradual decrease in the susceptibility of
      vancomycin during the 8-year-period was detected, but no vancomycin resistant S.
      aureus strains were isolated.

PMID- 12791468
TI  - Antimicrobial resistance in Gram-negative bacteria from Intensive Care Units and
      Urology Services. A nationwide study in The Netherlands 1995-2000.
AB  - A nationwide 6-year surveillance of resistance in Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa from clinical specimens
      of patients from ten Intensive Care Units and ten Urology Services was started in
      1995. MICs of amoxycillin, amoxycillin/clavulanate, trimethoprim, cotrimoxazole,
      norfloxacin, ciprofloxacin, cefaclor, ceftazidime, imipenem and gentamicin were
      determined by broth microdilution. Intensive Care Units had higher resistance
      levels of amoxycillin/clavulanate, cefaclor and ceftazidime (P<0.005) and lower
      resistance levels of nitrofurantoin, trimethoprim, cotrimoxazole and quinolones
      (P<0.01) than Urology Services. Changes in MIC distributions in time and
      development of resistant clusters were observed for nitrofurantoin (E. coli),
      amoxycillin (E. coli, P. mirabilis), amoxycillin/clavulanate (E. coli) and for
      quinolones (E. coli). The overall resistance level of ceftazidime and gentamicin
      was <5%, but this fluctuated with the appearance and disappearance of resistant
      clones in some Intensive Care Units. Quinolone resistance among P. aeruginosa
      from Intensive Care Units fluctuated between 7 and 14%.

PMID- 12791469
TI  - Rapid emergence of resistance to penicillin and trimethoprim-sulphamethoxazole in
      invasive Streptococcus pneumoniae in Zimbabwe.
AB  - Pneumococcal pneumonia and meningitis are common infectious disease problems in
      people who are HIV seropositive in southern Africa. For many years two
      inexpensive antibiotics, penicillin and trimethoprim-sulphamethoxazole (TMP-SMX)
      had been effective in treatment, but recently resistance to these agents has been
      reported from many parts of the world. This study was designed to determine the
      antimicrobial resistance patterns in invasive pneumococci from hospital patients
      in Harare, Zimbabwe. A total of 160 isolates of Streptococcus pneumoniae from
      blood cultures and CSF cultures were examined. The isolates came from adults and
      children in hospital in Harare between 1994 and 2000. The majority of isolates
      came from HIV positive adults (74%) and children (75%). Isolates of pneumococci
      with an MIC of 1.0 mg/l or more were first seen in 1997 and by 2000 they made up
      35% of all isolates. Significantly more isolates from HIV seropositive patients
      (50%) showed reduced susceptibility to penicillin compared with isolates from HIV
      seronegative patients (16%), and high level resistance (MIC 1.0 mg/l or higher)
      was found in 16% isolates from HIV positive patients compared with 6% isolates
      from HIV seronegative patients. Resistance to TMP-SMX was common, with more than
      50% isolates from HIV positive and HIV negative patients having reduced
      susceptibility to this antibiotic combination.

PMID- 12791470
TI  - Target site bacterial killing of cefpirome and fosfomycin in critically ill
      patients.
AB  - We employed an in-vivo pharmacokinetic/in-vitro pharmacodynamic method to
      simulate bacterial killing in plasma and the interstitium of skeletal muscle
      tissue after intravenous administration of 2 g of cefpirome and 8 g of fosfomycin
      alone and in combination to patients with sepsis. Interstitial antimicrobial
      concentrations were determined by use of in-vivo microdialysis. CFU/ml of
      Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (clinical isolate)
      decreased by approximately 2log(10) for plasma and muscle tissue 6 h after
      cefpirome and fosfomycin administration compared with the baseline, respectively.
      The simulation of plasma and tissue pharmacokinetics for the combined
      administration of these antibiotics resulted in complete eradication of S. aureus
      within 5 h after drug exposure. No bacterial re-growth occurred in any of the
      simulations within 6 h. The in-vitro simulation of in-vivo plasma and tissue
      pharmacokinetics of cefpirome and fosfomycin has shown that both antimicrobial
      agents kill S. aureus and P. aeruginosa strains effectively after single dose
      administration. This effect was most pronounced by the combined use of these
      antimicrobial agents. Therefore, this data corroborates antimicrobial strategies
      of simultaneous administration of cefpirome and fosfomycin in patients with
      severe soft tissue infection.

PMID- 12791471
TI  - Efficacy and pharmacodynamics of gemifloxacin versus levofloxacin in guinea pig
      pneumococcal pneumonia induced by strains with decreased ciprofloxacin
      susceptibility.
AB  - Quinolone in vivo bactericidal activity was investigated in a guinea pig
      pneumonia model using three Streptococcus pneumoniae strains with decreasing
      susceptibility to ciprofloxacin. Treatment regimens resulted in values of AUC(0
      24 h) and C(30 min) similar to those of standard oral regimens in human serum.
      Efficacy was defined as a significant difference in number of viable bacteria in
      the lungs compared with the control. Ciprofloxacin, levofloxacin and gemifloxacin
      were effective against the levofloxacin-susceptible strain. Only gemifloxacin
      achieved a >/=99.9% reduction versus control against the levofloxacin
      intermediate-resistant strain. Gemifloxacin achieved a 99.69% reduction and was
      the only quinolone significantly different from the control (P<0.05) against the
      levofloxacin-resistant strain. Gemifloxacin offers in vivo activity against
      ciprofloxacin- to levofloxacin-resistant pneumococci.

PMID- 12791472
TI  - Inhibitory and bactericidal activities of gemifloxacin and other antimicrobials
      against Mycoplasma pneumoniae.
AB  - The MIC of gemifloxacin was compared with that of sparfloxacin, levofloxacin,
      moxifloxacin, gatifloxacin, ciprofloxacin, doxycycline, erythromycin,
      azithromycin and clarithromycin using 97 clinical isolates of Mycoplasma
      pneumoniae. MBCs of fluoroquinolones were determined for a subgroup of 12
      isolates. Macrolides were the most potent agents with MIC(90)s for all drugs
      <or=0.001 mg/l. The doxycycline MIC(90) was 0.5 mg/l. Gemifloxacin MICs ranged
      from <or=0.001 to 0.25 mg/l. The gemifloxacin MIC(90) (0.125 mg/l) was equivalent
      to moxifloxacin and gatifloxacin, was 2-fold lower than sparfloxacin, 8-fold
      lower than levofloxacin and 32-fold lower than ciprofloxacin. MBCs for
      gemifloxacin were predominantly within 2-4 times the corresponding MIC values,
      indicating a bactericidal effect.

PMID- 12791473
TI  - In vitro activity of garenoxacin against recent clinical isolates of Chlamydia
      pneumoniae.
AB  - The in vitro activities of garenoxacin, a novel des-F (6)-quinolone,
      levofloxacin, moxifloxacin and clarithromycin were tested against 30 recent
      clinical isolates of Chlamydia pneumoniae. The minimal inhibitory concentration
      (MIC) at which 90% of the isolates were inhibited and the minimal bactericidal
      concentration (MBC) at which 90% of the isolates were killed by garenoxacin for
      C. pneumoniae was 0.03 mg/l (range 0.015-0.03 mg/l).

PMID- 12791474
TI  - The in vitro effects of faropenem on lower respiratory tract pathogens isolated
      in the United Kingdom.
AB  - Faropenem is a new oral penem with a structure different from current beta
      lactams including carbapenems. The susceptibility of Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis to faropenem, a macrolide, a
      beta-lactam, a beta-lactam/beta-lactamase inhibitor combination and two
      fluoroquinolones was investigated. S. pneumoniae was the most susceptible of the
      three species to faropenem. The MIC(90)s of faropenem against M. catarrhalis and
      H. influenzae were 0.5 and 1 mg/l, respectively. They were similar to amoxiclav
      (MIC (90)s of 0.25 and 0.5 mg/l). The quinolones showed strong activity against
      H. influenzae. A cluster analysis of the activities of amoxycillin and faropenem
      demonstrated a direct relationship between the two antimicrobial agent's
      activities and resistance profiles against both S. pneumoniae and H. influenzae.

PMID- 12791475
TI  - In vitro activity of new fluoroquinolones and linezolid against non-tuberculous
      mycobacteria.
AB  - The objective of the study was to determine the activity of new fluoroquinolones
      and linezolid against 108 clinical isolates of different species of non
      tuberculous mycobacteria isolated in Spain. Gatifloxacin and moxifloxacin were
      found to be more effective than levofloxacin. Mycobacterium kansasii was more
      susceptible to the fluoroquinolones tested than M. avium complex and M. fortuitum
      was more susceptible than M. chelonae. Linezolid was more active against M.
      kansasii than against M. avium complex. A better understanding of the
      relationship between the in vitro activity of these compounds and their
      usefulness in the treatment of these infections is needed. The new
      fluoroquinolones exhibit good activity against M. kansasii and M. fortuitum and
      linezolid is active against M. kansasii.

PMID- 12791476
TI  - Fosfomycin inhibits NF-kappaB activation in U-937 and Jurkat cells.
AB  - Fosfomycin exerts anti-inflammatory effects through inhibiting the production of
      proinflammatory cytokines. Transcription of the genes for these proinflammatory
      cytokines is regulated by NF-kappaB. We tested the hypothesis that fosfomycin
      inhibits the activation of NF-kappaB induced by tumor necrosis factor-alpha (TNF
      alpha) in human monocytic U-937 cells, and a T cell line (Jurkat). Western blot
      analysis demonstrated that fosfomycin inhibits NF-kappaB activation in both
      cells. Flow cytometry revealed that fosfomycin suppresses NF-kappaB activation in
      both cells in a dose-related manner. These findings are consistent with the idea
      that fosfomycin suppresses the production of proinflammatory cytokines via
      inhibition of NF-kappaB activation.

PMID- 12791477
TI  - Emergence of linezolid-resistant Enterococcus faecium during treatment of
      enterococcal infections.

PMID- 12791478
TI  - Initial disk diffusion quality control guidelines for tylosin tested against
      Staphylococcus aureus ATCC 25923 and Streptococcus pneumoniae ATCC 49619.

PMID- 12791479
TI  - Erythema multiforme-type drug eruption due to ethambutol with eosinophilia and
      liver dysfunction.

PMID- 12791480
TI  - Anti-lipase activity of Unsei-in against Propionibacterium avidum in the human
      axilla.

PMID- 12791481
TI  - Evaluation of a synergistic combination between the non-antibiotic microbicides
      diclofenac and trifluoperazine.

PMID- 12791482
TI  - Analysis of pro-inflammatory cytokine production in mouse spleen cells in
      response to the lantibiotic nisin.

PMID- 12791483
TI  - The meanings of organ donation: Muslims of Pakistani origin and white English
      nationals living in North England.
AB  - This study explores the meanings of organ donation, with emphasis on donating
      eyes and hearts, comparing people across gender and across two ethnic groups.
      Four focus group interviews were conducted with people living in the North of
      England: (1) five Muslim women of Pakistani origin, (2) five Muslim men of
      Pakistani origin, (3) nine white English women, and (4) eight white English men.
      The focus group interviews were analysed using grounded theory and a conceptual
      micro-model created for each group. The main finding was that the act of organ
      donation can be perceived as involving a personal cost. The Muslims of Pakistani
      origin related costs with their religious beliefs. In contrast, the white English
      associated costs with their distrust of the medical system. Women were concerned
      about the transmission of disease or of personality, whereas the white English
      men highlighted their personal rights. We conclude that the meaning of organ
      donation is more than about being and having a body. It is bound up in metaphors
      of embodiment, religious considerations, and moral judgement of scientific and
      medical conduct.

PMID- 12791484
TI  - The new genetics and its consequences for family, kinship, medicine and medical
      genetics.
AB  - In the past several decades there has been an explosion in our understanding of
      genetics. The new genetics is an integral part of contemporary biomedicine and
      promises great advances in alleviating disease, prolonging human life and leading
      us unto the medicine of the future. The aim of this paper is to explore the ways
      in which people make sense of the uncertainties that are associated with the new
      genetics, which by definition involve family and kinship relations. We explore
      the degree to which medical genetics places the patient in a double bind between
      the qualitative certainty and quantitative uncertainty of genetic inheritance
      that reinforce notions both of fear, and control of a person's future health.
      Second, we propose that the new genetics has medicalized family and kinship
      creating profound ethical and practical dilemmas for both the individual and for
      medicine as a whole.

PMID- 12791485
TI  - Examining the disablement process among older Mexican American adults.
AB  - The Disablement Process model (Verbrugge and Jette, Social Science & Medicine 38
      (1994) 1) describes a pathway leading from pathology to impairment to functional
      limitations, and, ultimately to disability. Components of this model have been
      examined among older White adults; however, very little research has examined the
      disablement process among older adults of other ethnic groups. Our goal in this
      research is to evaluate the Disablement Process model using Activities of Daily
      Living (ADL) disability as the outcome among a representative group of older
      Mexican American adults in the Southwestern United States. Respondents are from
      two waves of the Hispanic Established Populations Epidemiologic Study of the
      Elderly (EPESE) (n=2439). Structural equation models (LISREL 8.30) are utilized
      to examine the Disablement Process model. We also investigate aspects of the
      original model that have potentially important effects on the process of becoming
      disabled, such as cognitive impairment and perceived emotional support. Findings
      from structural equation models suggest that the main pathway from pathology to
      ADL disability is through functional limitations among older Mexican Americans.
      Risk factors, especially age and gender, have significant indirect effects on ADL
      disability. The main pathway in the Disablement Process model receives
      preliminary support among older Mexican Americans. We discuss implications of
      this model for future research.

PMID- 12791486
TI  - A politico-economic analysis of decision making in funding health service
      organisations.
AB  - From a normative perspective, conventional economic analysis is often used to
      establish a framework in which social objectives can be built into the decision
      making process. The health economics literature, however, tends to overlook the
      positive analysis of decision making--often assuming particular social objectives
      that may or may not correspond with reality. This perhaps explains why exercises
      in health economics priority setting on occasions break down. This study is a
      positive analysis of group decision making. It examines the process of
      deliberating upon proposed changes to funding arrangements across Divisions of
      General Practice in Queensland, Australia. Existing levels of funding had, for a
      number of years, largely been determined by an allocation formula. The motivation
      for this study was a perceived inequity created by the long-term under-funding of
      smaller (resource poor or 'marginal') Divisions. The challenge in this project
      was that any change in funding arrangements required the support of all the
      Divisions but also would potentially create 'winners' and 'losers'. Decision
      making within such an institutional context was rendered a zero sum game. This
      paper documents a consultative process whereby the relevant stakeholders, with
      clear interests in any decision, were asked to participate in deliberations as to
      how such a problem should be tackled. The objective was, in the face of adverse
      incentives, to derive recommendations for addressing existing shortfalls
      experienced by some of these Divisions. The process involved encouraging relevant
      players to take into consideration the global allocation issues and to move
      beyond their localised interests. The results indicate that such a process can be
      effective in not only generating the necessary goodwill to enable such group
      decision making, but also in establishing a more realistic set of policy
      recommendations.

PMID- 12791487
TI  - "It wasn't the plague we expected." Parents' perceptions of the health and
      environmental impact of opencast coal mining.
AB  - This paper explores the health and environmental concerns of parents living close
      to opencast coal mines in the UK and characterises parental risk perceptions in
      relation to children's asthma status. This qualitative research was undertaken in
      tandem with an epidemiological investigation aiming to establish whether opencast
      coal mining adversely affected children's respiratory health. Using a social
      construction approach, the centrality of health claims in environmental health
      disputes becomes apparent for a number of claims-makers. We focus on claims of
      non-activist participants in an epidemiological study, hitherto unknown and
      unexplored. In all but one case health claims were anticipated rather than
      realised. No link was found between children's asthma and exacerbation of the
      condition although some parents of children with asthma had greater concerns
      during the opencast planning stage. In fact, parents' discourses on children's
      health largely mirrored the epidemiological findings which showed increased dust,
      no increase in asthma prevalence but higher rates of general practitioner (GP)
      consultations for respiratory conditions suggesting that the commonly observed
      lack of convergence between lay and expert knowledge should not be taken for
      granted. In spite of this overall lack of an experienced health effect, the
      sociological data highlight respondents' recognition of the place-specificity of
      exposures, hence, the reasons why opencast proposals are likely to continue to be
      met with opposition. Environmental health studies which incorporate
      epidemiological and social approaches simultaneously have a better chance of
      arriving at conclusions meaningful to affected communities and facilitate greater
      understanding of environmental disputes.

PMID- 12791488
TI  - The health politics of asthma: environmental justice and collective illness
      experience in the United States.
AB  - While public health, medical, government, and community actors agree that there
      is a serious asthma epidemic, there is significant disagreement over the role of
      outdoor environmental factors in causing or triggering asthma. The outcome of
      these disputes is important because it substantially influences the focus of
      public health prevention and government regulation. Minority communities in the
      United States have higher morbidity rates than white communities and, as a
      result, are more readily affected by debates over environmental factors and
      subsequent public health and government efforts. Therefore, asthma has figured
      prominently in community activists' agendas concerning health inequalities. We
      compare and contrast the efforts of two community environmental justice
      organizations that include asthma as part of their overall community organizing
      efforts. We explore obstacles and strategies common to both groups as well as key
      differences in their orientation vis-a-vis science. To do so, we first discuss
      the discovery, current research, community action, and resultant changes in the
      understanding of the disease, specifically within poor and minority communities.
      Then, to offer a context to examine our two examples of asthma activism, we
      explore the social discovery of asthma and its environmental correlates, along
      with the political and economic conflicts surrounding asthma research and
      regulation. Using examples from the two activist groups, we discuss common
      approaches to address asthma in poor and minority communities such as challenging
      "transit racism", employing an environmental justice perspective, and using
      education to empower community members. Finally, we explore how the issues raised
      in terms of asthma and the environment lead to a collective form of illness
      experience, in which people with asthma make direct links to the social
      determinants of their health.

PMID- 12791490
TI  - Socio-demographic predictors of self-rated health in the Republic of Ireland:
      findings from the National Survey on Lifestyle, Attitudes and Nutrition, SLAN.
AB  - Though Ireland continues to have a poor health profile compared with other
      European Union countries, previous research on social variations has been
      limited. For the first time in the Republic of Ireland, the influence on self
      rated health of various socio-demographic indicators was assessed in a multi
      variate logistic regression model, separately for men and women. Data were from
      the first National Survey of Lifestyles, Attitudes and Nutrition, SLAN, conducted
      by post in a multi-stage, cluster random sample across 26 counties. There were
      6539 respondents (45.4% males). Mean self-rated health differed significantly
      according to age, marital status, tenure, educational status, social class,
      household size and eligibility for general medical services (GMS), but not
      according to gender or rurality. There were also differences if residing in a
      district with low level of affluence, or according to social cluster groupings.
      There were numerous significant correlations between the nine socio-demographic
      measures, but the most consistent pattern was between GMS eligibility and the
      various indicators, for both men and women. In the case of men, whether social
      class was included in the multi-variate model or not, education status remained
      predictive in the final model, (OR 2.36 CI 1.35-4.12) as did smoking status (OR
      2.11 CI 1.47-3.02). Odds ratio for GMS eligibility was 3.33 (CI 2.61-4.26)
      attenuated to 1.70 (CI 1.12-2.56) in the final model. For women the pattern was
      somewhat different. Only GMS status (OR 2.64 CI 1.74-3.99) and level of education
      (2.25 CI 1.19-4.24) were predictive in the final model. A multi-level analysis
      showed that area level of affluence was not significantly predictive of self
      rated health when individual level factors were taken into account.

PMID- 12791489
TI  - The health impact of health care on families: a matched cohort study of hospice
      use by decedents and mortality outcomes in surviving, widowed spouses.
AB  - Alternative ways of caring for seriously ill patients might have implications not
      only for patients' own outcomes, but also, indirectly, for the health outcomes of
      their family members. Clinical observation suggests that patients who die "good
      deaths" may impose less stress on their spouses. Consequently, we sought to
      assess whether hospice use by a decedent is associated with decreased risk of
      death in surviving, bereaved spouses. We conducted a matched retrospective cohort
      study involving a population-based sample of 195,553 elderly couples in the USA.
      A total of 30,838 couples where the decedent used hospice care were matched using
      the propensity score method to 30,838 couples where the decedent did not use
      hospice care. Our principal outcome of interest was the duration of survival of
      bereaved widow/ers. After adjustment for other measured variables, 5.4% of
      bereaved wives died by 18 months after the death of their husband when their
      deceased husband did not use hospice and 4.9% died when their deceased husband
      did use hospice, yielding an odds ratio (OR) of 0.92 (95% CI: 0.84-0.99) in favor
      of hospice use. Similarly, whereas 13.7% of bereaved husbands died by 18 months
      when their deceased wife did not use hospice, 13.2% died when their deceased wife
      did use hospice, yielding an OR of 0.95 (95% CI: 0.84-1.06) in favor of hospice
      use. Our findings suggest a possible beneficial impact of hospice--as a
      particularly supportive type of end-of-life care--on the spouses of patients who
      succumb to their disease. Hospice care might attenuate the ordinarily increased
      mortality associated with becoming widowed. This effect is present in both men
      and women, but it is statistically significant and possibly larger in bereaved
      wives. The size of this effect is comparable to the reductions in the risk of
      death seen in a variety of other modifiable risk factors in women. Health care
      may have positive, group-level health "externalities": it may affect the health
      not only of patients but also of patients' family members.

PMID- 12791491
TI  - Born out of wedlock and never married--it breaks a man's heart.
AB  - This study examines whether men who were born outside marriage in early twentieth
      century Sweden run a higher risk of dying from ischaemic heart disease (IHD) in
      middle and old age compared to men who were born inside marriage. Analyses are
      based on the male half of the Uppsala Birth Cohort Study, Sweden, consisting of
      all 7411 boys who were born alive at the Uppsala Academic Hospital during the
      period 1915-1929. The statistical method used is Cox regression. The results
      demonstrated a statistically significant excess mortality among men born outside
      marriage, which could not be explained by either social class of origin or birth
      weight for gestational age. Instead, this elevated mortality was largely
      explained by the more than doubled mortality risk among those men born outside
      wedlock who never married in relation to the corresponding group of men born to
      married parents. Even when three indicators of adult socio-economic status were
      adjusted for, men who never married and were born outside marriage still ran a 93
      per cent higher risk of dying from IHD than men who never married but were born
      inside marriage. This intervening effect of adult marital status was restricted
      to the category of never married men. Thus, although divorcees demonstrated an
      even higher mortality risk in relation to the married than did those who never
      married, this was equally true for men born inside and men born outside marriage.
      In the concluding section of the paper I argue that these findings should be
      understood in terms of the childhood social stigma that the illegitimate children
      experienced. This stigma may have resulted in an increased susceptibility, which
      in combination with the "failure" in adulthood to comply with the established
      norms of society regarding matrimony led to higher levels of IHD mortality in
      middle and old age.

PMID- 12791492
TI  - Language barriers between nurses and asylum seekers: their impact on symptom
      reporting and referral.
AB  - The objective of this study was to determine whether language barriers during the
      screening interview affected the reporting of asylum seekers' health problems and
      their referral to further health care. Seven hundred and twenty-three standard
      screening questionnaires, administered by nurses to asylum-seekers at the time of
      entry into Geneva/Switzerland between June and December 1998, were reviewed, as
      well as information pertaining to language use during the interview. Language
      concordance between nurses and asylum seekers was assessed by considering the
      presence/absence of an interpreter, the type of interpreter present (trained,
      untrained), and the nurse's self-assessed proficiency in the language used during
      the medical interview. Nurses also recorded their own subjective assessment of
      the overall quality of communication during the interview. More than half of the
      asylum seekers came from Europe, mainly the Balkan regions, and a third of them
      from Africa. Most asylum seekers were men (72%). The median age was 26.5 years,
      and 50% were younger than 25 years. Severe physical and psychological symptoms
      were reported by 19% and traumatic events prior to migration were reported by
      63%. The nurses referred 36% of all refugees to further medical care and 6% to
      psychological care. Professional interpreters were used in 8% of the interviews
      and ad hoc interpreters in 16%. Adequate, partial and inadequate language
      concordance was reported for 54%, 27% and 18% of the consultations respectively.
      Adequate language concordance was significantly associated with higher reporting
      of past experience of traumatic events and of severe psychological symptoms,
      contrasting with much fewer referrals to psychological care when language
      concordance was inadequate. These results suggest the importance of addressing
      language barriers in primary care centres in order to adequately detect and refer
      traumatised refugees. To address this problem, the use of professional
      interpreters is recommended.

PMID- 12791493
TI  - Self-treatment and its discussion in medical consultations: how is medical
      pluralism managed in practice?
AB  - Recent policy changes in the UK such as deregulation of prescribed medicines and
      the introduction of telephone helpline services are intended to promote self
      treatment. Drawing on interviews with, and consultations between, 35 patients and
      20 general practitioners, we use Kleinman's (Patients and Healers in the context
      of culture: an exploration of the Borderland between Anthropology, Medicine and
      Psychiatry, University of California Press Ltd., London) model of the three
      sectors of health care in order to examine the range of self-treatments people
      use and the discussion of these treatments in medical consultations. We argue
      that despite the availability of a range of treatment options and policy changes
      advocating greater use of self-treatment, patients are inhibited from disclosing
      prior self-treatment, and disclosure is affected by patients' perceptions of the
      legitimacy of self-treatment. The findings are in keeping with Cant and Sharma's
      (A New Medical Pluralism, Alternative Medicines, Doctors, Patients and the State,
      UCL Press, London) contention that although there has been a pluralisation of
      "legitimate" providers of health care and a restructuring of expertise,
      biomedicine itself remains dominant.

PMID- 12791494
TI  - Pharmaceutical reform and physician strikes in Korea: separation of drug
      prescribing and dispensing.
AB  - Before the recent pharmaceutical reform in Korea that mandates the separation of
      drug prescribing and dispensing, physicians and pharmacists both prescribed and
      dispensed drugs, resulting in the overuse and misuse of drugs. The pharmaceutical
      reform attempts to change the provider's economic incentives by eliminating the
      providers' profit from drugs that have been a major source of their income. It
      also influences the pharmaceutical industry that has thrived on offering high
      margins to physicians rather than on producing high-quality drugs. However,
      physician strikes forced the government to modify some critical elements of the
      reform package and to raise medical fees substantially to compensate for the
      income loss of physicians. Lack of a strategic plan of implementation, failure to
      appreciate the change in the paradigm of health policy process, and failure to
      convince consumers of the benefits of the reform, are the major reasons that the
      historic reform of the separation of drug prescribing and dispensing has resulted
      in greater social cost than expected.

PMID- 12791495
TI  - Epidemiological transition: model or illusion? A look at the problem of health in
      Mexico.
AB  - This paper discusses the validity of the epidemiological transition model to
      interpret changes in the structure of mortality and morbidity. Epistemological
      and political questions are posed. The case of Mexico is used to illustrate the
      limitations its use imposes on understanding the constellation of components
      explaining the epidemiological profile, and the problems involved in designing a
      public health policy on the basis of this sort of misinterpretation. It is
      suggested that the illusory certainty of a pre-determined destiny distorts the
      prospective that would enable to construct scenarios; what is actually happening
      remains hidden by the model and health policies are designed without adequate
      parameters for evaluating their effective impact. We conclude with some remarks
      on the usefulness of constructing alternative forms of interpretation for
      understanding changes in the epidemiological profile, one of the most important
      inputs for designing better policies to face the challenges posed by health care
      and dealing with illness in modern-day societies.

PMID- 12791496
TI  - Geographic analysis of diabetes prevalence in an urban area.
AB  - The objective of this research is to identify the sociodemographic,
      environmental, and lifestyle factors associated with the geographic variability
      of Diabetes Mellitus (DM) prevalence in the City of Winnipeg, Manitoba in Canada.
      An ecological regression study design was employed for this purpose. The study
      population included all prevalent cases of DM in 1998 for Winnipeg. Predictor and
      outcome data were aggregated for analysis using two methods. First, the spatial
      scan statistic was used to aggregate study data into highly probable diabetes
      prevalence clusters. Secondly, predictor and outcome data were aggregated to
      existing administrative health areas. Analysis of variance and spatial and non
      spatial linear regression techniques were used to explore the relationship
      between predictor and outcome variables. The results of the two methods of data
      aggregation on regression results were compared. Mapping and statistical analysis
      revealed substantial clustering and small-area variations in the prevalence of DM
      in the City of Winnipeg. The observed variations were associated with variations
      in socioeconomic, environmental and lifestyle characteristics of the population.
      The two methods of data aggregation used in the study generated very similar
      results in terms of identifying the geographic location of DM clusters and of the
      population characteristics ecologically correlated to those clusters. High rates
      of DM prevalence are strongly correlated with indicators of low socioeconomic
      status, poor environmental quality and poor lifestyles. This analysis further
      illustrates what a useful tool the spatial scan statistic can be when used in
      conjunction with ecological regression to explore the etiology of chronic
      disease.

PMID- 12791497
TI  - Sexual violence among a cohort of injection drug users.
AB  - The objective of this study was to determine the prevalence of, and factors
      associated with, sexual violence in childhood, adolescence and adulthood, among
      injection drug using men and women. The Vancouver Injection Drug User Study is a
      prospective cohort of injection drug users (IDU) begun in 1996. The analysis
      included all individuals who completed the baseline questionnaire who responded
      to a question about sexual assault. Multivariate modeling was used to determine
      and to what extent a history of sexual violence at different ages is predictive
      of HIV risk and other health risk behaviors. HIV prevalence was calculated as the
      total current number of HIV-positive individuals in the cohort. Of the 1437
      eligible individuals, 36% reported a lifetime history of sexual violence; 68% of
      women, and 19% of men (p<0.001). After adjusting for fixed sociodemographics,
      these individuals were more likely to have ever been in the sex trade, to
      knowingly share needles/rigs with HIV-positive people, to have attempted suicide,
      to have ever accidentally overdosed, to binge on alcohol, and to have been
      diagnosed with a mental disorder/disability. The prevalence of child sexual abuse
      in this cohort is 21%; 33% for women, and 13% for men. The data show a dose
      response relationship between age at first sexual violence and most risk
      behaviors examined. These relationships are further mediated by gender. The
      prevalence of HIV among individuals who ever experienced sexual violence was 25%,
      compared to 19% among those who never experienced sexual violence (p=0.006).
      Sexual violence, and especially child sexual abuse, is highly prevalent among
      this cohort, particularly among women. Child sexual abuse has worse consequences
      for both genders than sexual violence later in life. Nevertheless, women and men
      are affected differently by sexual violence at different ages, and this has
      significant implications for health promotion programs, and specifically HIV
      prevention.

PMID- 12791498
TI  - Hospitalisation process seen by patients and health care professionals.
AB  - Appropriate use of hospitalisation is an important concern in most countries.
      Previous studies have relied on professional opinion regarding the
      appropriateness of hospital stays, neglecting the patients' point of view. The
      purpose of this cross-sectional study was to assess the patients' point of view
      about the appropriateness of their hospital stay and to evaluate agreement with
      health care providers' opinions. It was undertaken in a medical rehabilitation
      division of the University Hospitals of Geneva in Switzerland. Patients reported
      their opinion on the justification of their hospital stay on the day of the
      interview, the reason why they judged their stay to be appropriate, and the place
      where they should be if not. The patients' health care providers answered the
      same questions. Two-hundred and fifty-four patients contributed to the evaluation
      of 314 days of hospitalisation. Only 20 hospital days (6%) were considered
      unjustified by patients, compared to 63 (20%) by health care providers (p<0.001).
      There was no agreement between these two judgements (Kappa=0.00,95% CI: -0.09 to
      +0.09). Similarly, there was little or no agreement concerning the reasons
      justifying the stay (Kappa=0-0.47) and concerning discharge planning. These
      results suggest that the definition of an appropriate hospital stay is complex
      and depends upon each actor's point of view. Better communication between
      patients and health care providers about decisions related to the hospitalisation
      process would be desirable.

PMID- 12791499
TI  - Breast cancer and obesity: an update.
AB  - Obesity has a complicated relationship to both breast cancer risk and the
      clinical behavior of the established disease. In postmenopausal women,
      particularly the elderly, various measures of obesity have been positively
      associated with risk. However, before menopause increased body weight is
      inversely related to breast cancer risk. In both premenopausal and postmenopausal
      breast cancer, the mechanisms by which body weight and obesity affect risk have
      been related to estrogenic activity. Obesity has also been related to advanced
      disease at diagnosis and with a poor prognosis in both premenopausal and
      postmenopausal breast cancer. Breast cancer in African-American women,
      considering its relationship to obesity, exhibits some important differences from
      those described in white women, although the high prevalence of obesity in
      African-American women may contribute to the relatively poor prognosis compared
      with white American women. Despite the emphasis on estrogens to explain the
      effects of obesity on breast cancer, other factors may prove to be equally or
      more important, particularly as they relate to expression of an aggressive tumor
      phenotype. Among these, this review serves to stress insulin, insulin-like growth
      factor-I, and leptin, and their relationship to angiogenesis, and transcriptional
      factors.

PMID- 12791500
TI  - Conjugated linoleic acid content in breast adipose tissue of breast cancer
      patients and the risk of metastasis.
AB  - The association between the level of conjugated linoleic acid (CLA) in breast
      adipose tissue at the time of diagnosis and the subsequent development of
      metastasis was examined in a cohort of 209 patients presenting with an initially
      localized breast cancer. CLA level in breast adipose tissue was used as a
      qualitative biomarker of its past dietary intake. Biopsies of adipose tissue were
      obtained at the time of initial surgery. A CLA-enriched fraction was prepared by
      high performance liquid chromatography and CLA measured as a percentage of total
      fatty acids, using capillary gas chromatography. Mean CLA level was low (0.44% of
      total fatty acids) and the range between patients was narrow (0.19-0.85). With a
      median follow-up time of 7.5 yr, 45 patients developed metastases. A Cox
      proportional hazard regression model was used to identify prognostic factors. We
      did not find any significant association between CLA level in adipose fat and
      either the prognostic factor (tumor size, nodal status, histoprognostic grade,
      mitotic index, and estrogen or progesterone receptors) or the risk of metastasis
      or death. We concluded that CLA are unlikely to be involved in survivorship.
      However, the hypothesis that a higher intake of CLA might have a protective
      effect on the risk of metastasis cannot be ruled out from these data, since the
      level of CLA in breast cancer patients' adipose tissue is likely to be too low
      and the range of CLA distribution too narrow for any protection to be detectable.

PMID- 12791501
TI  - Alcohol consumption and endometrial cancer: some unresolved issues.
AB  - The role of hormonal factors, in particular unopposed estrogens, on endometrial
      cancer occurrence is well established. Progesterone deficiency has also been
      suggested as a possible risk factor. Alcohol use has been shown to be associated
      with elevated estrogen levels and reduced progesterone. Epidemiologic studies,
      however, have not offered much support for a positive association between alcohol
      intake and endometrial cancer, with results generally indicating no association
      or suggesting an inverse relationship with endometrial cancer. However, certain
      methodologic limitations, such as small sample size, limited range of alcohol
      intake, and confounding may have explained those findings. Moreover, there are
      some unexplored aspects of the possible effect of alcohol, such as the possible
      interaction with use of exogenous estrogens, and other factors, that need
      clarification.

PMID- 12791502
TI  - Prognostic value of dietary intake and inflammation on survival in patients with
      advanced cancer: relationship with performance status, pain, and digestive
      disorders.

PMID- 12791503
TI  - Modulation of dietary vitamins E and C fails to ameliorate b-carotene
      exacerbation of UV carcinogenesis in mice.
AB  - b-Carotene is a strong singlet oxygen quencher and, under most conditions,
      exhibits strong antioxidant properties. Based on these properties, and a number
      of epidemiological studies, it was suggested that an above average intake of the
      carotenoid might reduce cancer risks. Earlier studies had found that b-carotene,
      when added to commercial closed-formula rodent diets, provided significant
      photoprotection to ultraviolet light (UV) carcinogenesis. However, clinical
      trials found that b-carotene supplementation evoked no change in incidence of
      nonmelanoma skin cancer and that smokers suffered a significant increase in lung
      cancer incidence. Further, recent studies, employing b-carotene-supplemented
      semidefined diets, not only failed to find a photoprotective effect, but
      significant exacerbation of UV carcinogenic expression resulted. Based on the
      relative electron transfer rate constants for interactions between b-carotene, a
      tocopherol (vitamin E), and vitamin C, a mechanism was proposed for the repair of
      b-carotene radical cation, a strongly oxidizing radical resulting from b-carotene
      interactions with many oxidizing species. It was theorized that vitamin C
      repaired the carotenoid radical cation. As mice have no nutritional requirement
      for vitamin C and smokers are known to exhibit low levels of the vitamin, it was
      suggested that differences in the relative levels of vitamin C in closed-formula
      rations (no vitamin C) in which photoprotection occurred, and semidefined diets
      (containing vitamin C) in which exacerbation resulted, might account for the
      differences in response. Hairless mice were fed b-carotene-supplemented
      semidefined diets containing varying levels of vitamins E and C (either
      increasing their concentrations or reducing them to reflect levels found in
      closed-formula rations) and subjected to a UV carcinogenesis protocol. Increasing
      levels of vitamins E and C did not ameliorate b-carotene exacerbation of UV
      carcinogenesis. Nor did elimination of vitamin C from the diet. Reduced levels of
      dietary vitamin E augmented b-carotene exacerbation of UV carcinogenic
      expression, suggesting vitamin E and b-carotene interaction. It is concluded that
      the photoprotective effect of b-carotene reported earlier by others, or the
      noninjurious effect of b-carotene found in our studies with closed-formula
      rations, might depend on interaction with other dietary factors that are either
      absent, or present in ineffectual concentrations, in the semidefined diet in
      which exacerbation of UV carcinogenesis occurs. Those factors could be other
      carotenoids, their isomers, or some yet unidentified phytochemical(s).

PMID- 12791504
TI  - Effects of commonly consumed fruit juices and carbohydrates on redox status and
      anticancer biomarkers in female rats.
AB  - Administration of apple juice, black currant juice, or a 1:1 combination of the
      two juices significantly decreased the level of the lipid peroxidation biomarker
      malondialdehyde in plasma of female rats, whereas the protein oxidation biomarker
      2-amino-adipic semialdehyde, was significantly increased following administration
      of orange juice, black currant juice, or the 1:1 combination of apple and black
      currant juice. A significant increase in 2-amino-adipic semialdehyde was also
      observed in control rats given sucrose, fructose, and glucose in the drinking
      water at concentrations approximating the average carbohydrate levels in the
      employed fruit juices. None of the fruit juices were found to affect the
      activities of antioxidant enzymes in red blood cells or hepatic glutathione S
      transferase. Hepatic quinone reductase activity, on the other hand, was
      significantly increased by grapefruit juice, apple juice, and black currant
      juice. The total daily intake of a selected subset of flavonoid aglycones ranged
      from 0.2 to 4.3 mg, and quercetin was found to be a minor constituent of all the
      juices investigated. In a parallel study, rats were fed quercetin at doses
      ranging from 0.001 to 10 g/kg of diet. However, no effects were observed on
      hepatic glutathione S-transferase or quinone reductase activities, plasma redox
      status, or the activity of red blood cell antioxidant enzymes. Overall, the
      results of the present study suggest that commonly consumed fruit juices can
      alter lipid and protein oxidation biomarkers in the blood as well as hepatic
      quinone reductase activity, and that quercetin may not be the major active
      principle. The observation that natural carbohydrates are capable of mediating
      oxidative stress in vivo warrants further studies due to the central role refined
      and unrefined carbohydrates play in human nutrition.

PMID- 12791505
TI  - Suppression of altered hepatic foci development by curcumin in wistar rats.
AB  - Curcumin, a yellow pigment of turmeric (Curcuma longa), is a commonly used spice
      and a coloring agent in foods, drugs, and cosmetics. Curcumin is known to possess
      chemopreventive properties in various animal tumor models. In the present study
      the effect of curcumin on the development of altered hepatic foci (AHF), by using
      a medium term liver bioassay, has been evaluated. AHF were analyzed by
      quantitative stereology using the Leica Qwin Image Analysis system from frozen
      liver sections stained for g-glutamyl transferase, adenosine triphosphatase,
      glucose-6-phosphatase, alkaline phosphatase, and placental isozyme of glutathione
      S-transferase. A significant protection on diethylnitrosamine (DEN) initiated and
      2-acetylaminofluorene (AAF) promoted AHF by curcumin was observed on these
      biological markers. The curcumin administration was found to restore the normal
      levels of the enzymes glutathione S-transferase and g-glutamyl transferase in rat
      liver following DEN-AAF exposure. Similarly, a significant protection was
      provided by curcumin in the enzyme-deficient foci for the adenosine
      triphosphatase-, alkaline phosphatase-, and glucose-6-phosphatase-treated groups
      in comparison to the DEN-AAF-treated group. These results show that curcumin can
      effectively suppress the DEN-induced development of AHF in rat liver.

PMID- 12791506
TI  - Specific amino acid dependency regulates invasiveness and viability of androgen
      independent prostate cancer cells.
AB  - Androgen-independent prostate cancer is resistant to therapy and is often
      metastatic. Here we studied the effect of deprivation of tyrosine and
      phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), in vitro on human
      DU145 and PC3 androgen-independent prostate cancer cells, and on nontumorigenic
      human infant foreskin fibroblasts and human prostate epithelial cells.
      Deprivation of the amino acids similarly inhibited growth of DU145 and PC3 cells,
      arresting the cell cycle at G0/G1. Met and Tyr/Phe deprivation induces apoptosis
      in DU145, but only Met deprivation induces apoptosis in PC3 cells. The growth of
      normal cells is inhibited, but no apoptosis is induced by amino acid deprivation.
      Tyr/Phe deprivation inhibits expression and phosphorylation of focal adhesion
      kinase (FAK) and extracellular-regulated kinase (ERK) in DU145 but not PC3 or
      normal cells. Met deprivation inhibits phosphorylation but not protein expression
      of FAK and ERK in PC3. Therefore, apoptosis of DU145 and PC3 cells by amino acid
      restriction is FAK and ERK dependent. Tyr/Phe and Met deprivation inhibits
      invasion of DU145 and PC3, but Gln deprivation only inhibits invasion of DU145
      cells. This indicates that the inhibition of invasion is not dependent on
      induction of apoptosis. The inhibition of invasion by Tyr/Phe restriction in
      DU145 and Met restriction in PC3 is consistent with the inhibition on FAK/ERK
      signaling. The inhibition of Tyr/Phe restriction in PC3 and Gln restriction in
      DU145 is not associated with inhibition of FAK/ERK. This indicates that FAK/ERK
      dependent and independent pathways are modulated by specific amino acid
      restriction. This study shows the potential for specific amino acid restriction
      to treat prostate cancer.

PMID- 12791507
TI  - Enhancement of glutathione and g-glutamylcysteine synthetase, the rate limiting
      enzyme of glutathione synthesis, by chemoprotective plant-derived food and
      beverage components in the human hepatoma cell line HepG2.
AB  - Glutathione (GSH) is an important antioxidant and cofactor of detoxifying
      metabolism. Therefore, elevation of GSH as achieved by inducing g
      glutamylcysteine synthetase (GCS), the limiting enzyme of GSH synthesis, may
      contribute to chemoprevention against cancer. In previous animal studies,
      increases in GCS were mainly found in liver and other organs that are not easily
      accessible in humans. Thus, employment and evaluation of alternative systems such
      as human-derived cell lines are encouraged. In the present experiment, we used
      the hepatoma cell line HepG2 to investigate the response of GCS and GSH to five
      plant-derived chemoprotectants contained in regularly consumed foodstuffs and
      beverages (kahweol/cafestol [K/C] [15.5-62.0 mM], a-angelicalactone [100-400 mM],
      benzyl isothiocyanate [1.7-5.0 mM], diallyl sulfide [175-700 mM], and quercetin
      [10-50 mM]). All treatments led to dose-dependent increases in both GCS activity
      and GSH concentration. Time course studies with K/C indicated that the
      enhancement of GCS preceded that of GSH, suggesting a causal relationship. K/C
      did not enhance g-glutamyl transpeptidase, a further enzyme that assists GSH
      related chemoprotection. Although GCS induction has been suggested to require an
      initial short-lived GSH depletion, we did not find any decrease in GSH after 3 h
      of incubation with K/C. In summary, HepG2 cells were shown to be a useful model
      to investigate the capacity of potential chemoprotectants to enhance GCS and GSH.
      To our knowledge, the present study is also the first to show increases in GCS by
      K/C and a-angelicalactone in vitro and by diallyl sulfide and quercetin in any
      system.

PMID- 12791508
TI  - Butyrate restores motile function and actin cytoskeletal network integrity in apc
      mutated mouse colon epithelial cells.
AB  - Loss of function of the Apc gene product is an early and frequent event in
      colorectal carcinogenesis. Altered migration of intestinal epithelial cells has
      been described in vivo in the Min mouse Apc+/Min model. Using cell lines
      established from this model we show in vitro that Apc+/Min cells are less motile
      than Apc+/+ cells and exhibit a disordered actin cytoskeletal network. This would
      increase the probabilities of the initiated cell to acquire additional genetic
      alterations leading to neoplasia. Butyrate, a product of indigestible
      carbohydrate fermentation by the colonic flora, is able to restore both motility
      and actin cytoskeletal organization. This feature may contribute to explain the
      protective effect exerted by butyrogenic diets on colon carcinogenesis in animal
      models.

PMID- 12791509
TI  - 1,25-dihydroxyvitamin D inhibits vitamin E succinate-induced apoptosis in
      C3H10T1/2 cells but not Harvey ras-transfected cells.
AB  - In this study, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on regulation
      of apoptosis was compared in control C3H10T1/2 mouse fibroblast cells and those
      transfected with the Harvey ras oncogene. A known apoptotic stimulator, vitamin E
      succinate (VES), reduced cell number in a time- and dose-dependent manner in both
      cell types. In an assay for viable cells, there were significantly more C3H10T1/2
      cells cotreated with VES and 1,25(OH)2D3 (-5.0 +/- 10.5% of vehicle-treated
      controls) compared to VES alone treated cells (-60.8 +/- 5.6%). In contrast,
      1,25(OH)2D3 did not change the percentage of viable cells following treatment by
      VES in ras-transfected cells [-67.3 +/- 7.5%, VES alone compared to 57.3 +/-v
      15.7% with VES and 1,25(OH)2D3 ]. Further studies confirmed that 1,25(OH)2D3
      inhibited VES-mediated apoptosis (1.27 +/- 0.34-fold over vehicle control)
      compared to VES treatment alone (2.29 +/- 0.56-fold increase) in C3H10T1/2 cells,
      but not in ras-transfected cells [3.07 +/- 0.43-fold increase, VES treatment
      alone; 3.64 +/- 0.42-fold increase, VES and 1,25(OH)2D3]. Both C3H10T1/2 and ras
      transfected cells treated with VES had increased concentrations of cellular VES
      with very little change in a-tocopherol, indicating that the cells took up VES
      intact. In addition, both cell lines contained similar levels of nuclear vitamin
      D receptor (VDR); however, the ras-transfected cells had reduced VDRE
      transcriptional activity. In conclusion, VES exerts its effect intact and
      1,25(OH)2D3 preferentially protects C3H10T1/2 cells, whereas ras-transformed
      cells were not protected from VES-mediated apoptosis.

PMID- 12791510
TI  - Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in
      nontumorigenic breast epithelial cells.
AB  - Recent results from epidemiology, in vitro cell culture and in vivo (animal and
      human) studies have suggested the benefits of indole-3-carbinol (I3C) for the
      prevention of many types of cancer, including breast cancer. However, there are
      no reports, to the best of our knowledge, on the effect of I3C on isogenic
      nontumorigenic and tumorigenic breast epithelial cells, and there is a
      significant void in our understanding of the molecular mechanism(s) by which I3C
      induces apoptotic cell death in breast cancer cells. To fill this gap in our
      understanding, we conducted experiments to investigate the effects of I3C on an
      isogenic nontumorigenic (MCF10A) and tumorigenic (MCF10CA1a [CA1a]) breast
      epithelial cells. Here we show that CA1a cells are more sensitive to low
      concentration of I3C in terms of cell growth inhibition compared to MCF10A cells.
      We further report that I3C upregulates Bax/Bcl-2 ratio and downregulates Bcl-xL
      expression in CA1a cells but not in MCF10A cells. We also report, for the first
      time, that I3C induces Bax translocation to the mitochondria, causing
      mitochondrial depolarization, resulting in the loss of mitochondrial potential
      leading to the release of cytochrome c and subsequent cell death in CA1a cells
      but not in MCF10A cells. From these results, we conclude that I3C selectively
      induces apoptosis in breast cancer cells, but not in nontumorigenic breast
      epithelial cells, suggesting the potential therapeutic benefit of I3C against
      breast cancer.

PMID- 12791512
TI  - Chronic DNA damage and niacin deficiency enhance cell injury and cause unusual
      interactions in NAD and poly(ADP-ribose) metabolism in rat bone marrow.
AB  - Previous work has shown that niacin deficiency in rats increases the severity of
      ethylnitrosourea (ENU)-induced anemia and leukopenia and the long-term
      development of cancer. The current study was initially designed to characterize
      changes in bone marrow cell populations during ENU treatment in this model.
      Weanling Long-Evans rats were fed diets containing 0 or 30 mg/kg of added niacin
      for a period of 2-3 wk. ENU treatment started after 1 wk of feeding and consisted
      of either 4 or 8 doses of ENU delivered by gavage, every other day. Niacin
      deficiency (ND) alone caused a significant depression in nucleated red blood
      cells (30%), and a sporadic effect on granulocytes (+23% after 4 doses of
      vehicle, -29% after 8 doses of vehicle). ENU treatment, after only 4 doses,
      caused a large decline in the numbers of bone marrow cells, and this effect was
      enhanced by ND (ENU decreased lymphocytes by 66% in pair-fed (PF) and 86% in ND,
      granulocytes by 41% in PF and 64% in ND, and nucleated red blood cells by 63% in
      PF and 71% in ND). Cell cycle distribution suggested that bone marrow cells in
      niacin-adequate rats, but not ND rats, mounted a compensatory proliferative
      response during chronic ENU exposure. ND alone caused an 80% decrease in bone
      marrow NAD+ levels at all time points. Surprisingly, chronic exposure to ENU
      (which should cause DNA damage and NAD+ utilization) led to a 2.8-fold increase
      in NAD+ content in ND marrow cells. This finding led to a second study in which
      ND and niacin-adequate PF control rats received 7 doses of ENU or vehicle (CON),
      after which all rats received 1 dose of ENU. In this study, modestly enhanced
      bone marrow NAD+ in chronically treated PF rats was used to synthesize 2-fold
      greater amounts of poly(ADP-ribose) than seen after one acute dose of ENU, while
      this did not occur in chronically treated ND rats, in spite of a 2.8-fold
      increase in bone marrow NAD+. This study has shown that bone marrow cell
      populations are sensitized to ENU treatment by ND, that NAD+ pools are regulated
      in response to DNA damage, and that NAD+ localization and/or utilization in the
      nucleus is altered during ND and chronic DNA damage.

PMID- 12791511
TI  - Effects of soy isoflavones on apoptosis induction and G2-M arrest in human
      hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL
      downregulation, and Cdc2 kinase activity.
AB  - Genistein, biochanin-A, and daidzein, the predominant soy isoflavones, have been
      reported to lower the risk of cancer, but it is not known whether they protect
      against human hepatoma cancer. This study was designed to investigate their
      effects on cell growth, the cell cycle, and apoptosis induction in the human
      hepatoma cell lines, HepG2, Hep3B, Huh7, PLC, and HA22T. Genistein, biochanin-A,
      and daidzein inhibited growth of all five lines in a dose-dependent manner. DNA
      fragmentation studies and the TUNEL assay demonstrated that isoflavones caused
      tumor cell death by induction of apoptosis. Activation of caspase-3 and cleavage
      of the caspase-3 substrate, poly(ADP-ribose)polymerase, was seen in hepatoma
      cells after 24 hours' exposure to isoflavones. In addition, isoflavone
      cytotoxicity correlated with downregulation of Bcl-2 and Bcl-XL expression.
      Synergistic effects of the three isoflavones were observed on cell growth
      inhibition, apoptosis induction, and anti-apoptotic protein expression. Flow
      cytometry showed that genistein, but not biochanin-A or daidzein, induced
      progressive and sustained accumulation of hepatoma cancer cells in the G2/M phase
      as a result of inhibition of Cdc2 kinase activity. Coapplication of caffeine
      prevented this cell cycle arrest, but not apoptosis, showing that cell cycle
      arrest was not necessary for apoptosis. Furthermore, the isoflavones combination
      also had a significant tumor-suppressive effect in nude mice. These results
      suggest that isoflavones might be promising agents for the treatment of human
      hepatoma.

PMID- 12791513
TI  - Effects of acute hyperglycemia on endothelium-dependent vasodilation in patients
      with diabetes mellitus or impaired glucose metabolism.
AB  - Although impaired endothelial function is well known in patients with diabetes
      mellitus (DM), the precise mechanism and the factors that contribute to this
      dysfunction remain to be clarified. The authors examined the effect of acute
      hyperglycemia on endothelium-dependent vasodilation in patients with DM or
      impaired glucose metabolism in vivo by plethysmography. In eight patients with
      diabetes mellitus or impaired glucose metabolism, the vasodilatory response to
      acetylcholine at infusion rates of 7.5, 15, and 30 microg/min was studied in the
      fasting state and at two levels of hyperglycemia, which were achieved by the
      infusion of glucose, insulin, and somatostatin. The vasodilatory response to
      acetylcholine was measured by calculating the forearm blood flow ratio (FBFR),
      defined as the measured forearm blood flow at a specific acetylcholine infusion
      rate divided by the baseline forearm blood flow without acetylcholine infusion.
      The induction of hyperglycemia resulted in a significant reduction in FBFR for
      all rates of acetylcholine infusion. The FBFR at an acetylcholine infusion rate
      of 7.5 microg/min was 1.13 +/- 0.07 and 1.19 +/- 0.06 for stages 1 and 2,
      respectively, compared with 1.36 +/- 0.08 for stage 3 (p < .05). In addition, at
      an acetylcholine infusion rate of 30 microg/min, the reduction in FBFR was
      associated with the degree of hyperglycemia (3.72 +/- 0.51, 2.98 +/- 0.42, 2.42
      +/- 0.32 for stages 1, 2, and 3 glucose levels, respectively, at an acetylcholine
      infusion rate of 30 microg/min, p < .05 by analysis of variance [ANOVA]). The
      results show that the induction of hyperglycemia results in a significant
      attenuation of endothelial function, and suggests the importance of hyperglycemia
      in the development of endothelial dysfunction observed in patients with DM or
      impaired glucose metabolism.

PMID- 12791514
TI  - Differential responses of human umbilical and coronary artery endothelial cells
      to apoptosis.
AB  - Apoptosis, or programmed cell death, plays an important role not only in normal
      homeostasis but is increasingly implicated in a number of pathological processes.
      The contribution of apoptosis in the pathophysiology of coronary artery disease
      has been suggested. In this study, the authors compared the effects of inductive
      and suppressive signals as well as the two combined apoptotic signals during the
      early stages of apoptosis using two types of human endothelial cells isolated
      from the umbilical vein (HUVECs) and from the coronary artery (HCAECs) vascular
      beds as study targets. The authors demonstrated that HUVECs were more susceptible
      than HCAECs to apoptosis, as measured by a 2.5-fold increase in caspase-3
      activity, which in turn may suggest a different pattern in association to the
      apoptotic mechanism within each cell type. Under inducing conditions of
      apoptosis, a significant increase in tissue factor (TF) expression at both the
      mRNA and protein level in HUVECs compared to the level of TF expression in HCAECs
      was observed. These different responses of endothelial cell types potentially
      indicate unequal susceptibility to apoptosis, depending on their vascular bed
      origins, and emphasize the importance of cell-type and -origin considerations
      when selecting a study model of apoptosis and pathophysiology.

PMID- 12791515
TI  - Endothelium-dependent relaxation to poly-L-arginine in canine coronary arteries.
AB  - The endothelium-dependent relaxation elicited by poly-L-arginine was investigated
      in canine coronary arteries. Poly-L-arginine (10(-11) to 10(-7) M) induced
      concentration-dependent endothelium-dependent relaxation in segments of canine
      coronary arteries incubated with indomethacin. In the presence of indomethacin,
      arteries contracted with prostaglandin F2alpha and exposed also to ouabain,
      oxyhemoglobin, or N(omega)-nitro-L-arginine, as well as those contracted with 20
      mM of KCl, presented reduced endothelium-dependent relaxation to poly-L-arginine.
      The combination of N(omega)-nitro-L-arginine with indomethacin produced further
      reduction of endothelium-dependent relaxation in arteries contracted with
      prostaglandin F2alpha as well as in arteries contracted with 20 mM of KCl.
      However, only quinacrine or calmidazolium, both in presence of N(omega)-nitro-L
      arginine plus indomethacin, abolished the endothelium-dependent relaxation
      elicited by poly-L-arginine. The relaxation to poly-L-arginine was not
      significantly affected by glybenclamide. The present study demonstrates that in
      addition to the prostacyclin and nitric oxide-dependent mechanisms, poly-L
      arginine also elicits endothelium-dependent relaxation in canine coronary
      arteries, stimulating the release of endothelial relaxing factor(s) produced by
      the phospholipase A2 pathway, but independent of the cyclooxygenase pathway,
      which may cause hyperpolarization of the vascular smooth muscle.

PMID- 12791516
TI  - Mediation of vascular relaxation in epineurial arterioles of the sciatic nerve:
      effect of diabetes in type 1 and type 2 diabetic rat models.
AB  - Previously, the authors have reported that acetylcholine-induced vascular
      relaxation in epineurial arterioles of the sciatic nerve is mediated by nitric
      oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Furthermore,
      they have demonstrated that acetylcholine-induced vasodilation in these vessels
      is impaired in streptozotocin-induced (type 1) and ZDF obese (type 2) diabetic
      rats. In the present study, the authors sought to determine the effect of
      diabetes on NO- and EDHF-mediated vasodilation in epineurial arterioles. In
      epineurial arterioles from nondiabetic Sprague-Dawley rats, NO and EDHF are
      equivalent in regard to their contribution to acetylcholine-induced vascular
      relaxation. In contrast, NO accounts for a greater portion of acetylcholine
      induced vascular relaxation in normal glycemic ZDF lean rats. Following 4 weeks
      of hyperglycemia, the EDHF component of acetylcholine-induced vascular relaxation
      was totally inhibited in both streptozotocin-induced and ZDF obese diabetic rats.
      Vasodilation mediated by NO was still active in epineurial arterioles from both
      type 1 and type 2 diabetic rat models. These data suggest that diabetes causes an
      impairment in EDHF-mediated vascular relaxation and that interventions directed
      at improving EDHF production or bioactivity may improve vascular function in
      epineurial arterioles in diabetes.

PMID- 12791517
TI  - Radial artery remodeling in response to shear stress increase within
      arteriovenous fistula for hemodialysis access.
AB  - It is known that changes in blood flow induce vascular remodeling and that shear
      stress, the tractive force acting on the vessel wall due to blood flowing,
      influences endothelial cell function. The aim of the present study was to
      investigate the relation between changes in pulsatile shear forces and arterial
      remodeling in response to chronic elevation in blood flow within the radial
      artery. The authors studied vessel diameter, flow rate, and shear stress in the
      radial artery of uremic patients before and after surgical creation of a native
      arteriovenous fistula for hemodialysis access. For this purpose, the authors used
      echo-color-Doppler ultrasound to perform diameter and blood velocity
      measurements. Time-function blood flow rate and wall shear stress were calculated
      based on arterial diameter, center-line velocity wave-form, and blood viscosity,
      using a numerical method developed according to Womersley's theory for unsteady
      flow in tubes. The results confirmed that the radial artery diameter increases in
      response to a chronic increase in blood flow in uremic patients. Moreover, it
      seems that the radial artery dilates in such a way as to maintain the peak wall
      shear stress constant, suggesting that endothelial cells sense the maximum rather
      than the time-averaged wall shear stress. This finding may lead to further
      understanding of the mechanisms responsible for endothelial response to physical
      stimulation by flowing blood.

PMID- 12791518
TI  - Optimization of isolation and functional characterization of primary murine
      aortic endothelial cells.
AB  - In this study the authors sought to improve the technique of isolating and
      culturing murine aortic endothelial cells (MAECs) for future use in studying
      endothelium-specific roles in complex pathologies such as atherosclerosis. The
      authors utilized a transgenic mouse expressing green fluorescent protein (GFP)
      under control of the endothelial specific Tie-2 promoter, allowing the tracking
      of endothelial cells throughout the isolation and purification. Briefly, aortas
      were harvested, the adventitia was removed, and strips were placed lumen side
      down into Matrigel. After 14 days, endothelial cells were isolated from the total
      cell population by fluorescence-activated cell sorting (FACS) using the GFP
      signal. The authors confirmed the endothelial phenotype of sorted cells based
      upon endothelial-specific Griffonia simplicifolia lectin staining, uptake of
      acetylated low-density lipoprotein (LDL), and von Willebrand factor (vWF) and VE
      cadherin staining. The authors also confirmed the cells' ability to form tubes in
      Matrigel, and for cellular alignment with flow to occur following monolayer
      culture under unidirectional laminar shear stress but not following culture under
      oscillatory flow. Although GFP fluorescence--based vital sorting was used
      initially to optimize the isolation, the authors have verified that this method
      is applicable to the isolation of MAECs from other strains and backgrounds of
      mice through the use of other endothelial markers.

PMID- 12791519
TI  - Mouse endothelial CD40 expression does not play a role during the development of
      transplant arteriosclerosis.
AB  - Endothelial cells (ECs) are of major interest in allograft rejection. The authors
      and others have recently shown in different mouse allograft models that, during
      the development of transplant arteriosclerosis, donor ECs are replaced by
      recipient ECs. It was the aim of this study to characterize the phenotype of ECs
      during the development of transplant arteriosclerosis further, with particular
      interest in their capability to express CD40. Abdominal aortic allografts were
      transplanted across a full major histocompatibility complex (MHC) barrier using
      BALB/c (H-2d) mice as donors and C57BL/6 (H-2b) mice as transplant recipients.
      Aortic allografts were harvested on days 7 and 30 after transplantation and
      analyzed by double-immunohistochemistry for expression of CD40 and CD31. As the
      authors have previously shown that ECs in the aortic allograft model are of donor
      origin on day 7 after transplantation, whereas by day 30 donor ECs have been
      replaced by ECs of recipient origin, these two time points were chosen for
      analysis of CD40 expression. Double-immunohistochemistry for CD40 and CD31
      revealed no endothelial expression of CD40 at either time point. These initial
      results obtained with the anti-CD40 monoclonal antibody (mAb) (clone 3/23) were
      confirmed by two further experiments using two different anti-CD40 mAbs (clone
      HM40-3 and clone 1/10) that bind to epitopes of the CD40 receptor distinct to
      that of 3/23. Neither mAb revealed endothelial expression of CD40. Further
      analysis of the composition of the cellular infiltrate demonstrated that the
      majority of macrophages were CD40 positive. The data indicate that in this mouse
      model of aortic transplantation, neither recipient- nor donor-derived ECs express
      CD40 during the development of transplant arteriosclerosis. Therefore, in
      contrast to rat or human ECs, CD40 expression by mouse ECs does not seem to play
      a major role in this form of allograft rejection.

PMID- 12791522
TI  - Biomarkers of tobacco exposure or harm: application to clinical and
      epidemiological studies. 25-26 October 2001, Minneapolis, Minnesota.
AB  - Adverse outcomes from tobacco use may take decades to develop. Biomarkers are
      measures that can be used in the early stages of tobacco use to assess exposure
      to tobacco toxins or to predict adverse health outcomes with which they are
      associated. Examples of biomarkers include specific chemical components of
      tobacco or their metabolites; early biochemical, histological, or physiological
      effects; and early health effects. Mechanistically relevant and quantitatively
      valid biomarkers are essential for assessing the ultimate impact of new products,
      treatments, preventive measures, and public health policies on tobacco-related
      disease. The tobacco industry's recent introduction of a variety of new tobacco
      products or devices with implied claims of reduced health risks highlights the
      need to develop methods for assessing their potential for benefit or harm. A wide
      variety of biomarkers for tobacco exposure or harm has been studied. Although
      many questions about their use remain unanswered, substantial data exist
      regarding their validity and utility. This conference reviewed both the general
      issues surrounding biomarker use and the current state of knowledge regarding the
      most widely studied and promising biomarkers.

PMID- 12791524
TI  - Protecting children from environmental tobacco smoke (ETS) exposure: a critical
      review.
AB  - Environmental tobacco smoke (ETS) is a significant public health burden. This
      review summarizes empirical evidence for reducing residential ETS exposure in
      youth in 19 studies published between 1987 and 2002. Most studies have
      investigated minimal contact, physician office-based interventions, although some
      have been conducted in homes and have been more intensive. Interventions are
      compared based on study design, type of intervention, sample characteristics
      (asthmatic or healthy), goals, and outcomes, including effect sizes. The average
      effect size (Cohen's d) was .34, with a range from -.14 to 1.04. The evidence
      suggests that interventions can be effective in reducing children's exposure.
      More rigorous study designs, interventions of greater intensity and duration, and
      those based on sound behavior change theory have yielded the most promising
      results. Challenges and limitations in this area of study are examined. A model
      for ETS interventions is proposed, and directions for future research are set
      forth.

PMID- 12791525
TI  - Science for hire: a tobacco industry strategy to influence public opinion on
      secondhand smoke.
AB  - A review of internal tobacco company documents reveals that members of the
      tobacco industry and its corporate attorneys created an international scientific
      consultants program to influence public opinion on environmental tobacco smoke
      (ETS). This program was shaped as a "product" to protect the industry from
      international threats of smoking restrictions. Additionally, this program was
      used to promote a scientific backdrop supporting the industry's position on ETS
      that differed from regulatory agencies and published scientific research. In this
      report, we detail the pervasive nature of the so-called ETS Consultants Program,
      outline the wide range of activities undertaken by the consultants, and highlight
      the role of the industry's corporate attorneys in creating and managing this
      program. We suggest heightened monitoring of industry-created scientific
      organizations, further tobacco document research, and wide dissemination of such
      work.

PMID- 12791526
TI  - High levels of transdermal nicotine exposure produce green tobacco sickness in
      Latino farmworkers.
AB  - Green tobacco sickness (GTS) is an occupational illness that affects tobacco
      workers worldwide. This study tested whether GTS results from nicotine poisoning.
      Data collection was based on a prospective design in which 182 farmworkers were
      interviewed up to five times at biweekly intervals. A saliva sample was obtained
      at each interview. Examining four regression models in which salivary cotinine
      was evaluated as a mediator between behavioral risk factors and GTS, this
      analysis showed that nicotine causes GTS: 25 workers had 31 occurrences of GTS.
      Among nonsmokers, each increment increase in the natural log of cotinine
      increased the odds of GTS 2.11 times, adjusting for task and wet conditions.
      Treatment of GTS must address nicotine poisoning. GTS affects laborers with
      limited resources. Research must disclose the extent of this occupational illness
      and investigate ways to prevent it.

PMID- 12791527
TI  - Tobacco-specific nitrosamines in tobacco from U.S. brand and non-U.S. brand
      cigarettes.
AB  - Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens
      found in tobacco products. As part of collaborative efforts to reduce tobacco use
      and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC)
      carried out a two-phase investigation into the worldwide variation of the levels
      of TSNAs in cigarette tobacco. In the first phase, representatives of the World
      Health Organization (WHO) purchased cigarettes; scientists from the CDC
      subsequently measured the levels of TSNAs in tobacco from 21 different countries.
      Although the data collected from this initial survey suggested that globally
      marketed U.S.-brand cigarettes typically had higher TSNA levels than locally
      popular non-U.S. cigarettes in many countries, the number of samples limited the
      statistical power of the study. To improve statistical power and to ensure
      adequate sampling, the CDC conducted a second survey of 14 countries. In addition
      to the United States, the CDC selected the world's 10 most populous countries and
      three additional countries, so that at least two countries from each of the six
      WHO regions were represented. For each country, the CDC compared 15 packs of
      Marlboro cigarettes, which is the world's most popular brand of cigarettes, with
      15 packs of a locally popular non-U.S. brand in the study country. Marlboro
      cigarettes purchased in 11/13 foreign countries had significantly higher tobacco
      TSNA levels than the locally popular non-U.S. brands purchased in the same
      country. The findings suggest that TSNA levels in tobacco can be substantially
      reduced in some cigarettes.

PMID- 12791528
TI  - Environmental tobacco smoke exposure in low-income 6-year-olds: parent report and
      urine cotinine measures.
AB  - We examined the prevalence and level of environmental tobacco smoke (ETS)
      exposure using urine cotinine levels in children and three types of maternal self
      reports in a sample of 196 low socioeconomic status (SES) mothers and their
      children. The self-reports were report of the mother's own smoking, report of the
      number of household smokers, and report of the usual number of daily hours that
      the child was exposed to ETS. According to the reports, 59% of the children's
      mothers were current smokers, 71% of the children came from households with
      smokers, and 85% had daily exposure to ETS. Based on urine cotinine measures
      adjusted for creatinine, 79% of the children were identified as ETS exposed. The
      average urine cotinine level was 19.6 ng/mg, and the median cotinine level was
      13.1 ng/mg (range: 0-120 ng/mg). Correlations between urine cotinine levels and
      the three maternal reports were 0.48, 0.43, and 0.36, respectively. The most
      sensitive maternal report measure was number of hours of exposure per day when
      using adjusted urine cotinine levels of >/=5 ng/mg were used as the yardstick of
      exposure. Of the 154 children screened at the level of >/=5 ng/mg, 89.5% were
      also identified by maternal report as ETS exposed. However, 30 children whose
      mothers reported ETS exposure had urine cotinine levels of <5 ng/mg. These data
      showed that ETS exposure was prevalent in low-SES children and that the maternal
      reports identified a higher number of children as ETS exposed. The biological
      measures provided data on levels of recent exposure; however, level of exposure
      from biological measures correlated only moderately with the maternal report. A
      combination of a maternal report and a biological measure is suggested as the
      most informative estimate of ETS exposure in young children.

PMID- 12791529
TI  - Effects of nicotine on heart dimensions and blood volume in male and female rats.
AB  - The adverse effects of tobacco smoking on the cardiovascular system are well
      established. Effects of nicotine on the heart, in contrast, are not well
      characterized. Understanding specific effects of nicotine on the heart and on
      blood volume is relevant to (a) elucidating the mechanisms by which nicotine may
      contribute to heart disease and (b) determining potential risks associated with
      nicotine products used in smoking cessation or to treat various medical
      conditions. The present experiment investigated effects of continuous nicotine
      administration for 14 days (0, 6, or 12 mg/kg/day) on heart histopathology and
      blood volume (a measure of hemoconcentration) in 59 male and 59 female rats of
      two strains (Sprague-Dawley and Long-Evans). Following nicotine administration,
      animals were sacrificed and blood volume was measured. Heart length; heart
      weight; left ventricle, right ventricle, lateral wall, anterior wall, and
      posterior wall thicknesses; and intraventricular width (i.e., septum) were
      measured. Nicotine reduced heart weight, heart length, and overall blood volume.
      Females were more sensitive than males to the effects of nicotine on heart
      weight. In contrast, males were more sensitive than females to the effects of
      nicotine on heart length. Together, these findings suggest that males and females
      differ in their sensitivity to nicotine's cardiac effects.

PMID- 12791530
TI  - Measuring nicotine intake in population surveys: comparability of saliva cotinine
      and plasma cotinine estimates.
AB  - Both plasma and saliva cotinine levels have been reported in surveys of smoking
      behavior, and it is of interest to know how closely these two measures
      correspond. Plasma and saliva specimens were gathered from a sample of 605
      respondents in the 1998 Health Survey for England and assayed for cotinine by a
      well-proven gas chromatographic method. Plasma and saliva cotinine concentrations
      were highly correlated (r=.99). On average, concentrations in saliva were 25%
      higher than in plasma, and this ratio applied both at the low levels attributable
      to passive smoking and across the range of active smoking values. The ratio was
      somewhat lower in younger people than in older people and also varied
      significantly by body mass index but did not differ by gender. Calculation of the
      limits of agreement revealed substantial uncertainty in the predicted plasma
      value corresponding to a given saliva cotinine, and vice versa. For comparisons
      across subjects, the mean plasma cotinine level corresponding to a mean saliva
      cotinine level can be estimated with confidence, but at the level of the
      individual, considerable predictive uncertainty remains.

PMID- 12791531
TI  - Tobacco smoke exposure and decreased serum and red blood cell folate levels: data
      from the Third National Health and Nutrition Examination Survey.
AB  - The aim of this cross-sectional study was to determine the effects of smoke
      exposure on serum and red blood cell folate levels. Data collected as part of the
      Third National Health and Nutrition Examination Survey were analyzed. Serum and
      red blood cell folate levels were measured in active smokers and nonsmokers with
      high, moderate, and low exposure to environmental tobacco smoke. After adjusting
      for dietary intake of folate and other covariates, we found that both smokers and
      nonsmokers with high smoke exposure had lower red blood cell folate levels than
      did nonsmokers with low smoke exposure (-86 nmol/l [95% confidence interval, CI, 
      101 to -71 nmol/l] for smokers; -50 nmol/l [95% CI -69 to -31 nmol/l] for
      nonsmokers with high smoke exposure, compared with nonsmokers with low smoke
      exposure). Similarly, after adjustment of dietary intake of folate and other
      covariates, the log serum folate level also was decreased (-0.29 log nmol/l [95%
      CI -0.33 to -0.25 log nmol/l] for smokers; -0.16 log nmol/l [95% CI -0.20 to 
      0.12 log nmol/l] for nonsmokers with high smoke exposure, compared with
      nonsmokers with low smoke exposure). Tobacco smoke exposure is associated with
      decreased folate levels, which may be a mechanism for some of the health effects
      of active and passive smoking.

PMID- 12791532
TI  - Physicians' missed opportunities to address tobacco use during prenatal care.
AB  - Smoking cessation during pregnancy reduces the risk of adverse perinatal outcomes
      and leads to long-term cessation for at least some women smokers. Prenatal care
      offers repeated opportunities for smoking status identification and smoking
      cessation counseling. Using cross-sectional data from the 1991-1996 National
      Ambulatory Medical Care Survey, we assessed how frequently physicians caring for
      pregnant women identified pregnant women's smoking status and provided counseling
      to pregnant smokers. Data were available from 793 physicians reporting on 5,622
      office visits by pregnant patients from 1991 through 1996. Physicians identified
      pregnant women's smoking status at 81% of visits but provided smoking counseling
      at only 23% of visits by pregnant smokers. Physicians were less likely to
      identify smoking status of non-White pregnant women but no less likely to counsel
      non-White smokers. These results indicate a clear need to improve quality of care
      provided to pregnant women who use tobacco.

PMID- 12791533
TI  - Prenatal nicotine increases testosterone levels in the fetus and female
      offspring.
AB  - Epidemiological studies have shown that smoking during pregnancy markedly
      increases the risk for future tobacco use by adolescent female offspring. It has
      been hypothesized that the increased smoking risk in females is secondary to a
      nicotine-induced increase in fetal plasma testosterone levels that persist to
      adult life. To test this hypothesis, we randomized pregnant Sprague-Dawley rats
      to receive either saline or nicotine from Day 4 until the end of gestation. Blood
      samples for testosterone levels were obtained from 30- and 120-day-old offspring.
      In addition, blood samples for testosterone levels were obtained prior to and
      following a 2-day infusion of nicotine to chronically catheterized ovine fetuses.
      Maternal nicotine exposure resulted in increased plasma testosterone in 30-day
      old female rat offspring, with no differences found in nicotine-exposed males. In
      addition, plasma testosterone levels increased in ovine fetuses in response to
      the nicotine infusion. We conclude that prenatal nicotine exposure increases
      plasma testosterone levels chronically in adolescent female rat offspring and
      acutely in both male and female ovine fetuses. Although our findings lack
      correlative behavioral information on the female offspring, these data are
      consistent with human epidemiological data suggesting that prenatal environmental
      influences may have marked effects on the subsequent smoking behaviors of
      offspring.

PMID- 12791535
TI  - Comment on "The public health implications of smoking-induced decreased serum and
      red blood cell folate levels".

PMID- 12791534
TI  - Acceptability and validity of hair collection from Latino children to assess
      exposure to environmental tobacco smoke.
AB  - This study assessed the acceptability of collecting hair from Latino children to
      measure environmental tobacco smoke (ETS) exposure and examined the concurrent
      validity between nicotine and cotinine levels in children's hair in relation to
      adult reports of the children's ETS exposure. Trained Latina lay community health
      advisors recruited 143 Spanish-speaking Latino adult volunteers and their
      children. Bilingual-bicultural measurement technicians collected two types of
      data: (a) the adult's paper-and-pencil report about the child's past-month
      exposure to cigarettes in the home and car and (b) a sample of the child's hair
      to be analyzed for nicotine and cotinine. Of the eligible subjects, 8.5% declined
      to participate because of the hair collection protocol, some citing cultural
      beliefs. Among participants in the study, few problems arose related to hair
      collected, probably because of the culturally sensitive approach used during
      recruitment and measurement. Adults' reports of exposure, hair nicotine, and hair
      cotinine showed considerable variation and were skewed to the right. Average
      nicotine levels for these children appeared to be comparable to those reported
      elsewhere, whereas cotinine levels appeared to be somewhat lower. Hair nicotine
      was more detectable than hair cotinine and, compared with cotinine, showed a
      clearer linear relationship with adults' reports. However, associations between
      adults' reports and both biological measures were modest. Collecting hair samples
      in the field (i.e., participants' homes) to measure Latino children's ETS
      exposure is generally acceptable when appropriate methods are used. Hair nicotine
      may be a more valid and practical biological measure than hair cotinine. Hair
      sampling may be a potentially useful, noninvasive technique in ETS studies,
      although the modest associations of constituents in children's hair with adults'
      reports indicates that each measure provides different information about ETS
      exposure.

PMID- 12791536
TI  - Associations between smoking and heritable temperament traits.
AB  - Cloninger's neuropsychopharmacological theory identifies heritable temperament
      traits that are linked to neurotransmitter activity. We tested whether these
      traits were associated with smoking. The four temperament dimensions of the
      French-language version of the Temperament and Character Inventory were assessed
      in three distinct samples recruited on the Internet in 2000-2001. Novelty Seeking
      (NS) was measured in 775 people, Reward Dependence (RD) in 1,383 people, and Harm
      Avoidance (HA) and Persistence (P) in 823 people. HA (2.1 points, p.03) and NS
      (3.2 points, p.01) were lower in never-smokers than in ever-smokers. RD (.6
      point, p.01) and P (.5 point, p.01) were lower in former smokers than in current
      smokers. The level of tobacco dependence was associated with the NS subscore
      Extravagance (.1 point on the Heaviness of Smoking Index per point on
      Extravagance, p.01). Motivation to quit smoking was positively associated with
      the RD subscore Sentimentality (.1 point on a 0-10 scale of motivation per point
      on Sentimentality, p.01) and negatively with the HA subscore Fear of Uncertainty
      (.2 point of motivation per point, p.01). Among ex-smokers, age at smoking
      cessation was negatively associated with P (.5 year per point on P, p.02) and
      positively associated with the HA subscore Fatigability (.3 year per point, p.04)
      and with the NS subscore Disorderliness (.3 year per point, p.03). Smoking is
      associated with heritable temperament traits. Consequences for the treatment and
      prevention of tobacco dependence are discussed.

PMID- 12791537
TI  - Nicotine dependence and treatment outcome among African American cocaine
      dependent patients.
AB  - Despite a close association between tobacco and cocaine use, few studies have
      systematically examined whether smoking predicts an adverse outcome for cocaine
      dependent patients. We investigated whether severity of nicotine dependence was
      related to treatment outcome for cocaine-dependent individuals. Standardized
      assessments of nicotine dependence (Fagerstrom Test for Nicotine Dependence;
      FTND), cocaine use, and personality were obtained for 105 African American
      cocaine-dependent outpatients. Outcome measures included negative urine drug
      screens, days in treatment, dropout, and number of treatment sessions attended.
      The sample was stratified into cocaine-positive and cocaine-negative groups based
      on admission urine drug screens, and relationships between nicotine dependence
      and outcome measures were examined in each group. In the cocaine-negative group,
      higher FTND scores were negatively correlated with number of negative urine drug
      screens during treatment even after controlling for other predictors, whereas
      FTND scores were not correlated to outcome in the cocaine-positive group. It
      seems that severity of tobacco use predicts poor outcome for cocaine-dependent
      patients who are cocaine free at the time of admission into outpatient treatment.

PMID- 12791538
TI  - Tobacco cessation, oral pain, and psychological distress in Bangladeshi women.
AB  - This study reports the experience of oral pain and psychological distress
      following tobacco cessation in Bangladeshi women. A cross-sectional survey was
      carried out in which telephone interviews were conducted in the Sylheti language
      by two female Bangladeshi researchers using structured questionnaires. Study
      participants were 58 Bangladeshi women, aged 22-60 years, who had recently given
      up chewing paan-with-tobacco. The General Health Questionnaire (GHQ-12) was used
      to measure psychological distress. A questionnaire on pain description, location,
      duration, onset, and intensity also was administered. Logistic regression
      analysis was carried out to explore the relationships between psychological
      distress and age, chewing characteristics, and the oral pain experience. The
      response rate was 100%. Of the sample, 22% reported having pain for 2 days and
      28% for at least 1 week, 65% reported that the pain started by itself, 69%
      reported the intensity as mild or discomforting, and 52% experienced
      psychological distress. Significant predictors for high psychological distress
      were number of daily paan (odds ratio, OR=1.13), current tooth problem (OR=4.60),
      pounding pain (OR=6.50), pain onset (OR=3.21), and pain intensity (OR=5.57). The
      prevalence of oral pain reported for Bangladeshi women following an attempt at
      chewing tobacco cessation is high. Characteristics of this outcome suggest the
      pain is of dental origin. These characteristics are correlated to psychological
      distress. The success of chewing tobacco cessation initiatives in the population
      may be influenced by oral pain and psychological distress. Further research is
      needed to explore the etiological factors associated with oral pain in this group
      of tobacco users.

PMID- 12791539
TI  - Inhibition of rat respiratory-tract cytochrome P-450 isozymes following
      inhalation of m-Xylene: possible role of metabolites.
AB  - Xylene is used as a solvent in paints, cleaning agents, and gasoline. Exposure
      occurs primarily by inhalation. The volatility and lipophilicity of the xylenes
      make the lung and nasal mucosa the primary target organs. m-Xylene (m-XYL) has
      been shown to alter cytochrome P-450 (CYP) activity in an organ- and isozyme
      specific manner. The purpose of this work was to determine if the metabolism of m
      XYL to the inhibitory metabolite m-tolualdehyde (m-ALD) is the cause of
      inhibition of CYP isozymes following in vivo inhalation exposure to m-XYL (100,
      300 ppm), 3-methylbenzyl alcohol (3-MBA) (50, 100 ppm), or m-ALD (50, 100 ppm). A
      single 6-h inhalation exposure of rats to m-XYL inhibited pulmonary CYPs 2B1,
      2E1, and 4B1 in a dose-dependent manner. Inhalation of 3-MBA inhibited pulmonary
      CYPs 2B1 and 4B1 in a dose-dependent manner. m-ALD inhibited pulmonary CYPs 2B1
      and 2E1 in a dose-dependent manner, while 4B1 activity was increased dose
      dependently. Nasal mucosa CYP 2B1 and 2E1 activity was inhibited following
      exposure to m-XYL dose dependently, 3-MBA inhibited nasal mucosa CYPs 2E1 and 4B1
      dose dependently. CYPs 2B1, 2E1, and 4B1 were inhibited in a dose-dependent
      fashion following inhalation of m-ALD. Following high-performance liquid
      chromatography (HPLC) analysis, m-ALD was detected after in vivo exposure to m
      XYL, m-ALD, and 3-MBA in a dose-dependent manner, with highest m-ALD levels in
      the nasal mucosa and lung. Alteration of cytochrome P-450 activity by m-XYL could
      result in increased or decreased toxicity, changing the metabolic profiles of
      xenobiotics in coexposure scenarios in an organ-specific manner.

PMID- 12791540
TI  - Relative inhibitory potencies of chlorpyrifos oxon, chlorpyrifos methyl oxon, and
      mipafox for acetylcholinesterase versus neuropathy target esterase.
AB  - The relative inhibitory potency (RIP) of an organophosphorus (OP) inhibitor
      against acetylcholinesterase (AChE) versus neuropathy target esterase (NTE) may
      be defined as the ratio [k(i)(AChE)/k(i)(NTE)], where k(i) is the bimolecular
      rate constant of inhibition for a given inhibitor against each enzyme. RIPs
      greater than 1 correlate with the inability of ageable OP inhibitors or their
      parent compounds to produce OP compound-induced delayed neurotoxicity (OPIDN) at
      doses below the LD50. The RIP for chlorpyrifos oxon (CPO) is >>1 for enzymes from
      hen brain homogenate, and the parent compound, chlorpyrifos (CPS), cannot produce
      OPIDN in hens at sublethal doses. This study was carried out to test the
      hypothesis that the RIP for the methyl homologue of CPO, chlorpyrifos methyl oxon
      (CPMO), is >>1 and greater than the RIP for CPO. Mipafox (MIP), an OP compound
      known to produce OPIDN, was included for comparison. Hen brain microsomes were
      used as the enzyme source, and k(i) values (mean +/- SE, microM(-1) min(-1)) were
      determined for AChE and NTE (n = 3 and 4 separate experiments, respectively). The
      k(i) values for CPO, CPMO, and MIP against AChE were 17.8 +/- 0.3, 10.9 +/- 0.1,
      and 0.00429 +/- 0.00001, respectively, and for NTE were 0.0993 +/- 0.0049, 0.0582
      +/- 0.0013, and 0.00498 +/- 0.00006, respectively. Corresponding RIPs for CPO,
      CPMO, and MIP were 179 +/- 9, 187 +/- 4, and 0.861 +/- 0.011, respectively. The
      results demonstrate that RIPs for CPO and CPMO are comparable, markedly different
      from that for MIP, and >>1, indicating that CPS methyl, like CPS, could not cause
      OPIDN at sublethal doses.

PMID- 12791541
TI  - Immune alterations in mice exposed to the herbicide simazine.
AB  - Simazine, a triazine herbicide, was investigated for its in vivo immunomodulatory
      properties. Male C57Bl/6 mice were treated with vehicle or 300 or 600 mg/kg body
      weight (bw) simazine daily orally for 4 wk. The immune system was evaluated by
      the antibody response to sheep red blood cells (SRBC; plaque assay and serum
      immunoglobulin G), natural killer (NK) and macro-phage activities, lymphocyte
      subpopulations in the spleen and thymus, and concanavalin A (Con A)- and
      lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes.
      Body weight and spleen and thymus weight decreased generally in simazine-treated
      mice, while the weight of adrenal glands was higher than in the control. Simazine
      treatment (600 mg/kg) induced an increase in the percentage of CD4(+) cells in
      spleen and CD8 + in thymus. Simazine inhibited the IgM plaque-forming cell
      numbers and lowered the level of IgG and the proliferation of mitogen-stimulated
      B cells and T cells. In addition, splenic NK and peritoneal macrophage activities
      in exposed mice were significantly decreased. Exposure to simazine also decreased
      cytokine production by macrophages, such as interleukin-1 (IL-1), IL-6, and tumor
      necrosis factor-alpha (TNF-alpha). Taken together, data indicate that the immune
      system was suppressed by oral simazine exposure.

PMID- 12791543
TI  - Control of respirable dust and crystalline silica from breaking concrete with a
      jackhammer.

PMID- 12791542
TI  - Effect of frying-meat emission particulate on 17beta-estradiol 2- and 4
      hydroxylation in human lung adenocarcinoma CL5 cells.
AB  - The effect of airborne frying-meat emission particulate (FMEP) on metabolism of
      17beta-estradiol (E(2)) to potentially toxic catechol estrogens 2- and 4
      hydroxyestradiol (2- and 4-OH-E(2)) was determined using human lung
      adenocarcinoma CL5 cells treated with organic extracts of beef FMEP. E(2) was
      incubated with microsomes prepared from untreated CL5 cells or cells treated with
      200 microg/ml FMEP extract for 6 h. E(2) metabolites formed were analyzed by high
      performance liquid chromatography (HPLC). The results revealed that treatment
      with FMEP produced three-and twofold increases of 2- and 4-hydroxylation of E(2),
      respectively. Monooxygenase activity and immunoblot analyses showed that FMEP
      markedly induced microsomal 7-ethoxyresorufin O-deethylase (EROD) activity and
      cytochrome P-450 (CYP) IAI and CYPIBI protein levels. Similar increases in E(2)
      hydroxylation, EROD activity, and CYP protein levels were observed with HepG2
      human hepatoma and MCF-7 human breast cancer cells treated with FMEP or 1 microM
      dibenz[a,h]anthracene. Cotreatment of CL5 cells with FMEP extract and 2 microM
      alpha-naphthoflavone, an arylhydrocarbon receptor antagonist, blocked the
      inductive effects of FMEP on E(2) hydroxylation and EROD activity. Additions of
      0.01, 0.1, or 1 microM alpha-naphthoflavone, a CYP inhibitor, to microsomes
      produced concentration-dependent decreases in E(2) 2-hydroxylation and EROD
      activity of CL5 cells induced by dibenz[a,h]anthracene. The present finding
      demonstrates that FMEP can increase formation of 2-OH-E(2) and 4-OH-E(2) by human
      lung cells, and induction of CYP1A1 and CYP1B1 is a potential mechanism
      underlying increased E(2) metabolism. The toxicological significance of FMEP and
      estrogen interaction warrants further investigation.

PMID- 12791545
TI  - Application of a fluorometric method for the detection of mold in indoor
      environments.

PMID- 12791544
TI  - Styrene exposure in a fiberglass boat manufacturing operation.

PMID- 12791547
TI  - An asbestos job exposure matrix to characterize fiber type, length, and relative
      exposure intensity.
AB  - The relationship between asbestos exposure and disease has been well documented,
      although questions persist as to variation in risk by the type and length of
      fiber. For a series of jobs with potential asbestos exposure, the primary fiber
      type (e.g., amosite, anthophylite, chrysotile, crocidolite, or tremolite) and
      fiber length were identified and the relative exposure intensity was estimated.
      The resulting job exposure matrix may be useful in epidemiological studies where
      asbestos is an exposure of interest.

PMID- 12791548
TI  - Indoor air quality and occupational exposures at a bus terminal.
AB  - This article presents an assessment of indoor air quality at a bus terminal. For
      this purpose, field surveys were conducted, and air samples were collected and
      analyzed for the presence of selected indoor air quality indicators. Mathematical
      modeling was performed to simulate bus emission rates, occupational exposure, and
      ventilation requirements to maintain acceptable indoor air quality. A sensitivity
      analysis based on literature-derived emission rates estimates was conducted to
      evaluate the effect of seasonal temperature changes within the terminal. Control
      measures to improve indoor air quality at the terminal are also outlined. While
      carbon monoxide concentrations were below the corresponding American Conference
      of Governmental Industrial Hygienists' (ACGIH) standards under normal operating
      conditions, they exceeded the 8-hr recommended average standard at peak hours and
      the World Health Organization (WHO) standard at all times. Total suspended
      particulates levels, on the other hand, were above the 24-hr American Society of
      Heating, Refrigerating and Air Conditioning Engineers' (ASHRAE) standard. Carbon
      monoxide emission rates that were estimated using the transient mass balance
      model correlated relatively well with those reported in the literature. Modeling
      results showed that the natural ventilation rate should be at least doubled for
      acceptable indoor air quality. While pollutant exposure levels depended on the
      individual activity patterns and the pollutant concentration, pollutant emissions
      rates within the terminal were affected mostly by the temperature with a 20-25
      percent variation in carbon monoxide levels due to changes in seasonal
      temperatures.

PMID- 12791549
TI  - An exposure prevention rating method for intervention needs assessment and
      effectiveness evaluation.
AB  - This article describes a new method for (1) systematically prioritizing needs for
      intervention on hazardous substance exposures in manufacturing work sites, and
      (2) evaluating intervention effectiveness. We developed a checklist containing
      six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure
      potential versus protection (two columns) at the levels of materials, processes,
      and human interface (three rows). The three levels correspond to a simplified
      hierarchy of controls. Each of the six sets of indicator variables was reduced to
      a high/moderate/low rating. Ratings from the matrix were then combined to
      generate a single overall exposure prevention rating for each area. Reflecting
      the hierarchy of controls, material factors were weighted highest, followed by
      process, and then human interface. The checklist was filled out by an industrial
      hygienist while conducting a walk-through inspection (N = 131 manufacturing
      processes/areas in 17 large work sites). One area or process per manufacturing
      department was assessed and rated. Based on the resulting Exposure Prevention
      ratings, we concluded that exposures were well controlled in the majority of
      areas assessed (64% with rating of 1 or 2 on a 6-point scale), that there is some
      room for improvement in 26 percent of areas (rating of 3 or 4), and that roughly
      10 percent of the areas assessed are urgently in need of intervention (rated as 5
      or 6). A second hygienist independently assessed a subset of areas to evaluate
      inter-rater reliability. The reliability of the overall exposure prevention
      ratings was excellent (weighted kappa = 0.84). The rating scheme has good
      discriminatory power and reliability and shows promise as a broadly applicable
      and inexpensive tool for intervention needs assessment and effectiveness
      evaluation. Validation studies are needed as a next step. This assessment method
      complements quantitative exposure assessment with an upstream prevention focus.

PMID- 12791550
TI  - Health effects of indoor fungal bioaerosol exposure.
AB  - Occupational and environmental health professionals are confronted with issues
      concerning the health effects of indoor fungal bioaerosol exposure. This article
      reviews current data on the health effects of indoor mold exposure and provides
      practical suggestions for occupational and environmental health practitioners
      regarding how best to manage these exposures based on published human studies. We
      conducted MEDLINE searches and reviewed all English language studies on indoor
      mold exposure (visible survey or objective sampling) and human health effects
      published from 1966 to November 2002. The main findings of the studies are
      analyzed in conjunction with plausible association of health effects and fungal
      exposure. Five case control studies, 17 cross-sectional surveys, and 7 case
      reports met the selection criteria. Current evidence suggests that excessive
      moisture promotes mold growth and is associated with an increased prevalence of
      symptoms due to irritation, allergy, and infection. However, specific human
      toxicity due to inhaled fungal toxins has not been scientifically established.
      Methods for measuring indoor bioaerosol exposure and health assessment are not
      well standardized, making interpretation of existing data difficult. Additional
      studies are needed to document human exposure-disease and dose-response
      relationships.

PMID- 12791551
TI  - Coal tar pitch volatiles and polycyclic aromatic hydrocarbons exposures in
      expansion joint-making operations on a construction site: a case study.
AB  - This case study describes occupational exposures to coal tar pitch volatiles
      (CTPV) as benzene soluble fraction (BSF), polycyclic aromatic hydrocarbons (PAHs)
      and total particulates at a unique operation involving the use of coal tar in the
      making of expansion joints in construction of a multi-level airport parking
      garage. A task-based exposure assessment approach was used. A set of 32 samples
      was collected and analyzed for total particulate and CTPV-BSF. Twenty samples of
      this set were analyzed for PAHs. Current American Conference of Governmental
      Industrial Hygienists (ACGIH(R)) respective threshold limit value-time weighted
      average (TLV-TWA) for insoluble particulates not otherwise specified (PNOS) is 10
      mg/m(3) as inhalable dust, which roughly corresponds to 4 mg/m(3) total
      particulate; for CTPV as BSF the TLV is 0.2 mg/m(3), and for specific PAHs such
      as benzo(a)-pyrene (B[a]P), ACGIH suggests keeping exposure as low as
      practicable. The recommended Swedish exposure limit for B(a)P is 2 microg/m(3).
      The highest exposure levels measured were 12.8 mg/m(3) for total particulate, 1.9
      mg/m(3) for coal tar pitch volatiles as BSF, and 12.8 microg/m(3) for B(a)P.
      Several of the CTPV-BSF results were over the TLV of 0.2 mg/m(3). The data set is
      limited; therefore, caution should be used in its interpretation.

PMID- 12791552
TI  - Quantification of lead in telephone cord: use of x-ray photoelectron spectroscopy
      technique.
AB  - There have been historic concerns that lead has existed as a plasticizer in
      telephone lines, causing health hazards, especially for children, who frequently
      mouth, chew, and swallow non-food items. The acid environment of the mouth may
      leach lead from the surface into the saliva under non-destructive conditions.
      Thus, distinguishing the amount of lead in the surface versus the inside of the
      polyvinyl chloride (PVC) material covering the phone cord line is very important
      in assessing health hazards. Using X-ray Photoelectron Spectroscopy (XPS), we
      measured lead in the PVC covers of telephone cords that connect the handheld part
      of the phone to the base. Lead was detected in both the inner and outer surface
      of an older (approximately 12 years) cord (1.3 atomic percent in inner surface;
      0.4 atomic percent in the outer surface). However, when we tested four popular
      brands of newer cords (currently available in the market), there was no
      detectable lead. This study demonstrates that XPS is a useful technique that can
      distinguish lead contents between surface versus inner core of plasticized
      telephone cords. Telephone cords and other plasticized materials that may leach
      lead should be screened to establish safety.

PMID- 12791554
TI  - Primary intracerebral haemorrhage--clinical and radiologic predictors of survival
      and functional outcome.
AB  - PURPOSE: Primary intracerebral haemorrhage (ICH) is a common and devastating
      disorder that often results in long-term disability. This review examines the
      literature on predictors of survival and long-term functional outcome after ICH.
      METHOD: Medical literature review. RESULTS: Numerous clinical and radiologic
      variables have been shown to be associated with survival and functional recovery
      following ICH. These include patient age and gender, lesion size and location,
      initial level of consciousness, presence of intraventricular haemorrhage,
      hydrocephalus, and mass effect. Studies have employed a variety of outcome
      measures including survival and functional recovery. CONCLUSIONS: Clinical and
      radiologic findings following ICH may assist rehabilitation specialists as they
      develop treatment goals, anticipate long-term patient care needs, and educate and
      train caregivers.

PMID- 12791555
TI  - Defining quality of life for Chinese elderly stroke survivors.
AB  - PURPOSE: This study aimed to identify the constituents and conceptual
      characteristics of the quality of life (QOL) of Chinese elderly stroke survivors,
      living in the community in Hong Kong. METHOD: A triangulated approach was used to
      identify the QOL components for this population. This process involved a
      comparison of QOL components gathered from three different methods, namely, focus
      group interviews, review of the literature and the contents of the generic Hong
      Kong Chinese version of the World Health Organization Quality of Life Scale
      (CWHOQOL-HK). Five health professionals were involved in the comparison process.
      A percentage of inter-judge agreement was used to determine the reliability of
      the comparisons made between the judges. RESULTS: This study identified 36
      components considered to contribute to the QOL of Chinese elderly stroke
      survivors in Hong Kong. The conceptual characteristics of their QOL generally
      concurred with those identified in the literature. CONCLUSION: Both similarities
      and differences were found in the QOL components identified in this study when
      compared to those identified in studies of Western populations who are elderly
      and had a stroke. The contents of the CWHOQOL-HK scale were found to lack
      adequacy in representing the QOL of Chinese elderly stroke survivors in Hong
      Kong. Recommendations are given, based on the findings of this study, to overcome
      this limitation for its application as a QOL measure for this population.

PMID- 12791556
TI  - A survey of the effects of fatigue on driving in people with multiple sclerosis.
AB  - PURPOSE: To examine the effect of fatigue on driving in patients with multiple
      sclerosis (MS). METHOD: A questionnaire on driving was sent to 192 people with MS
      and 192 controls who were relatives or close friends of the people with MS.
      RESULTS: Replies were received from 75 MS patients (39%) and 63 controls (32%).
      MS patients' ability to drive was more often affected by fatigue, leg problems,
      numbness and eye problems than controls. The MS group reported driving shorter
      distances and shorter times than controls, and that fatigue had a significant
      effect on their ability to drive. The driving plans of MS patients were affected
      by fatigue. CONCLUSION: Fatigue affected the driving of MS patients, but it was
      not the only factor and should be considered in relation to other symptoms of MS.

PMID- 12791557
TI  - Pilot evaluation of a mindfulness-based intervention to improve quality of life
      among individuals who sustained traumatic brain injuries.
AB  - PRIMARY OBJECTIVE: To examine the potential efficacy of a mindfulness-based
      stress reduction approach to improve quality of life in individuals who have
      suffered traumatic brain injuries. RESEARCH DESIGN: Pre-post design with drop
      outs as controls. METHODS AND PROCEDURES: We recruited individuals with mild to
      moderate brain injuries, at least 1 year post-injury. We measured their quality
      of life, psychological status, and function. Results of 10 participants who
      completed the programme were compared to three drop-outs with complete data.
      EXPERIMENTAL INTERVENTION: The intervention was delivered in 12-weekly group
      sessions. The intervention relied on insight meditation, breathing exercises,
      guided visualization, and group discussion. We aimed to encourage a new way of
      thinking about disability and life to bring a sense of acceptance, allowing
      participants to move beyond limiting beliefs. MAIN OUTCOMES AND RESULTS: The
      treatment group mean quality of life (SF-36) improved by 15.40 (SD = 9.08)
      compared to - 1.67 (SD = 16.65; p = 0.036) for controls. Improvements on the
      cognitive-affective domain of the Beck Depression Inventory II (BDI-II) were
      reported (p = 0.029), while changes in the overall BDI-II (p = 0.059) and the
      Positive Symptom Distress Inventory of the SCL-90R (p = 0.054) approached
      statistical significance. CONCLUSIONS: The intervention was simple, and improved
      quality of life after other treatment avenues for these participants were
      exhausted.

PMID- 12791559
TI  - The relevance of education training for therapists in promoting the delivery of
      holistic rehabilitation services for young school children with disabilities in
      Hong Kong.
AB  - PURPOSE: To investigate the relevance of education training to occupational
      therapists and physiotherapists (therapists) in their delivery of rehabilitation
      services in early child educational settings in Hong Kong. METHOD: A qualitative
      study was carried out on seven therapists who were completing their educational
      studies at postgraduate level and six informed-consenting classroom educators,
      each of whom had worked with one of the therapists. A mainly open-ended
      questionnaire for collecting initial data was administered on the therapists, who
      were also requested to elaborate further on their responses. Concurrently,
      individual, audiotaped semi-structured interviews were held with the educators.
      The data were inductively analysed through categorical coding and themes derived
      separately for each group, with the authors reaching consensus in organizing the
      identified themes. RESULTS: The 100% response from the therapists revealed that
      they had acquired more confidence with increasing knowledge of educationally
      relevant issues and applied them in collaborative practice with educators. Their
      current programmes extended beyond unidisciplinary paediatric habilitation. The
      educators' interview transcripts supported these findings. Some ways of applying
      knowledge and delivering educationally-relevant therapy were discussed.
      CONCLUSIONS: Incorporation of education-training as continuing education for
      therapists employed in childhood educational settings is important for maximizing
      quality paediatric rehabilitation in these settings.

PMID- 12791558
TI  - Long-term injury related disability in Ghana.

PMID- 12791560
TI  - An exploration of the extent to which attending Headway enhances quality of life
      after traumatic brain injury.
AB  - PURPOSE: This paper explores the perception of quality of life (QOL) of four men
      following traumatic brain injury (TBI) and the effects of their injury on family,
      social and working life. METHOD: It also highlights their on-going difficulties
      6, 8, 10 and 11 years post injury and that long term support is not available
      from rehabilitation services often due to the NHS financial restraints. RESULTS:
      Participants in this study have highlighted: (a) the need for long term support
      over an unspecified continuum; (b) the value of peer support; (c) the value of an
      understanding environment prepared to address individual needs which encourages
      independence; (d) the need for a social outlet; (e) the benefit of structure and
      boundaries after rehabilitation; and (f) the need for ongoing information for the
      survivor and family. CONCLUSIONS: Headway, the brain injury association, has
      provided a continuum of care revealing a lengthy process of adjustment towards a
      new self, a new role and a new life.

PMID- 12791562
TI  - Analyzing development of working models for disrupted attachments: the case of
      hidden family violence.
AB  - This article offers a developmental model of attachment theory rooted in dynamic
      skill theory. Dynamic skill theory is based on the assumption that people do not
      have integrated, fundamentally logical minds, but instead develop along naturally
      fractionated strands of a web. Contrary to traditional interpretations of
      attachment theory, dynamic skill theory proposes that individuals continue to
      modify their working models of attachments throughout the lifespan. In
      particular, working models of close relationships develop systematically through
      a series of skill levels such that the skills vary across strands in the web and
      will not automatically form a unified whole. The continual modification of
      working models is particularly pertinent for the consequences of hidden family
      violence for individuals' development. Dynamic skill theory shows how trauma can
      produce not developmental delay or fixation, as has been proposed previously, but
      instead the construction of advanced, complex working models.

PMID- 12791563
TI  - Early preventive attachment-oriented psychotherapeutic intervention program with
      parents of a very low birthweight premature infant: results of attachment and
      neurological development.
AB  - The birth of a very small preterm infant (< or = 1500 grams) can be a
      traumatizing experience for many parents. A developmental risk model is presented
      that is the background to an early attachment-oriented preventive
      psychotherapeutic intervention. This comprehensive parent-centered intervention
      program is composed of supportive group psychotherapy, attachment-oriented focal
      individual psychotherapy, a home visit and video-based sensitivity training. The
      intervention aims at improving parental coping, the process of attachment and
      parent-infant interaction. In a prospective longitudinal design mothers were
      randomly assigned to a control (N = 44) and an intervention group (N = 43) after
      preterm delivery. Results show that the percentage of secure (control vs.
      intervention group: 77.8% vs. 59.4%) and insecure (control vs. intervention
      group: 8.3% vs. 31.3% avoidant, 13.9% vs. 9.4% ambivalent) attachment quality in
      high-risk preterm infants is comparable to results from studies with term
      infants. There was no significant statistical difference in terms of quality of
      attachment of the preterm infants between the control group and the intervention
      group. However, only in the control group, impaired neurological development
      corresponded significantly with an insecure quality of attachment, but not in the
      intervention group, although there were significantly more neurologically
      impaired infants in the intervention group. This result is discussed as an effect
      of the intervention program.

PMID- 12791564
TI  - Differentiating among insecure mother-infant attachment classifications: a focus
      on child-friend interaction and exploration during solitary play at 36 months.
AB  - Utilizing data from the NICHD Study of Early Child Care, the primary objective of
      the current report was to examine how avoidant and resistant mother - infant
      attachment classifications at 15 months were differentially associated with
      children's interaction with a same-sex friend and exploration during solitary
      play at 36 months. The added contributions of attachment security at 36 months
      and maternal sensitivity from 6 to 36 months to the prediction of child outcomes
      were also explored. As hypothesized, an avoidant attachment history was related
      to more instrumental aggression during child-friend interaction, whereas a
      resistant attachment history was associated with less self-assertion/control
      among friends and less attention and pretend play during exploration. Maternal
      sensitivity and concurrent attachment security also made unique contributions to
      the prediction of child outcomes at 36 months, although associations with 15
      month attachment remained significant when these subsequent measures of the
      mother - child relationship were considered. Few differences emerged for the
      disorganized mother - infant attachment category in this relatively low-risk
      sample. Results underscore the need to differentiate between avoidant and
      resistant attachment groups and illustrate how early attachment history and
      subsequent indices of the mother - child relationship contribute to children's
      functioning.

PMID- 12791565
TI  - Attachment and emotion experience in later life: the view from emotions theory.
AB  - Despite the large volume of research on attachment over the past three decades
      based on work with children and young adults, there has been scant attention to
      later life. As such, Bowlby's claim that attachment theory has implications for
      the entire lifespan remains relatively untested. In this paper we present
      exploratory data documenting the relations between attachment and emotion in
      older adults. A sample of 1118 community-dwelling adults ranging in age from 65
      to 86 years completed measures of attachment and Izard's (1972) Differential
      Emotions Scale. Consistent with a developmental-functionalist theory of emotions,
      different dimensions of attachment were associated with different emotion
      profiles, even when background variables were controlled. Attachment security was
      associated with less guilt, contempt, and shame, and with greater joy, sadness
      interest, fear and anger. Dismissingness, in contrast, was associated with
      greater interest and with less joy, shame, and fear. Finally, fearful avoidance
      was associated with greater joy, disgust, shame and anxiety. Taken together, our
      data suggest that the later life relations between emotion and attachment are
      similar to those documented in younger samples, although there appear to be some
      important developmental differences. The data are interpreted in the context of
      developmental-functionalist theories of emotions and implications for how
      emotions function within attachment systems and moderate social relations across
      the lifespan are discussed.

PMID- 12791566
TI  - Attachment in African American and European American older adults: the roles of
      early life socialization and religiosity.
AB  - The significance of attachment relationships in later life has recently emerged
      as an important topic of study. Yet little attention has focused on attachment
      dynamics among older minority adults. This paper extends the literatures on
      ethnicity, attachment, and later life by examining attachment patterns in two
      large community-dwelling samples of older (65 + years) African American (n = 671)
      and European American (n = 447) adults. Data gathered during face-to-face
      interviews included demographic information, adult attachment, early rearing
      experiences, and current religiosity. Hierarchical regression analyses revealed
      that adult attachment dimensions were differentially predicted by childhood
      socialization patterns and current religiosity. Significant ethnic differences in
      relations between adult attachment and childhood socialization practices also
      were found. The results highlight the importance of examining contextual
      differences in attachment in later life.

PMID- 12791568
TI  - CS-dependent response probability in an auditory masked-detection task:
      considerations based on models of Pavlovian conditioning.
AB  - Experimental studies were performed using a Pavlovian-conditioned eyeblink
      response to measure detection of a variable-sound-level tone (T) in a fixed-sound
      level masking noise (N) in rabbits. Results showed an increase in the asymptotic
      probability of conditioned responses (CRs) to the reinforced TN trials and a
      decrease in the asymptotic rate of eyeblink responses to the non-reinforced N
      presentations as a function of the sound level of the T. These observations are
      consistent with expected behaviour in an auditory masked detection task, but they
      are not consistent with predictions from a traditional application of the
      Rescorla-Wagner or Pearce models of associative learning. To implement these
      models, one typically considers only the actual stimuli and reinforcement on each
      trial. We found that by considering perceptual interactions and concepts from
      signal detection theory, these models could predict the CS dependence on the
      sound level of the T. In these alternative implementations, the animals response
      probabilities were used as a guide in making assumptions about the "effective
      stimuli".

PMID- 12791569
TI  - Elemental and configural encoding of the conditioned stimulus.
AB  - Five experiments explored the effect of conditioning AB and CD compounds on
      responding to transfer AD and BC compounds and to elements. These experiments
      used several conditioning procedures: flavour aversion and instrumental
      discriminative learning in rats and autoshaping in pigeons. All of the
      experiments found greater responding to the trained AB and CD than to the
      transfer AD and BC compounds, a result that agrees with some configural models,
      but not with an elemental model. All experiments also found greater responding to
      the transfer AD and BC compounds than to the elements, a result that agrees with
      elemental, but not configural, models.

PMID- 12791570
TI  - NMDA receptor activity and the transmission of sensory input into motor output in
      introverts and extraverts.
AB  - Recent research suggests that individual differences in brain dopamine
      functioning may be related to the personality dimension of extraversion. The
      major goal of the present study was to answer the question of whether a
      pharmacologically induced change in glutamatergic NMDA receptor activity would
      also differentially affect the transmission of sensory input into motor out-put
      in introverts and extraverts. Therefore, in a double-blind within-subjects
      design, either 30 mg of the NMDA receptor antagonist memantine or placebo were
      administered to 48 healthy male volunteers before performing a choice reaction
      time task. In introverts, memantine caused a pronounced increase in lift-off time
      (i.e., the time required to lift the finger from a home button) compared to that
      in extraverts, whereas movement time (i.e., the time required to move the finger
      from the home button to a response button) was decreased in both groups. The
      pattern of results suggests that extraversion-related differential sensitivity to
      pharmacologically induced changes in NMDA receptor activity is limited to
      functions that involve an interaction between the glutamatergic and dopaminergic
      systems.

PMID- 12791571
TI  - Representational blending in human conditional learning: Implications for
      associative theory.
AB  - In two experiments, participants were presented with pictures of different foods
      (A, B, C, D, X,) and learned which combinations resulted in an allergic reaction
      in a fictitious patient, Mr X. In Problem 1, when A or B (but not C or D) was
      combined with food X an allergic reaction occurred, and when C or D (but not A or
      B) was combined with Y an allergic reaction occurred. In Experiment 1,
      participants also received Problem 2 in which A, B, C, and D interacted with
      foods V and W either in the same way as X and Y, respectively, or in a different
      way. Participants performed more proficiently in the former than in the latter
      condition. In Experiment 2, after training on Problem 1, participants judged
      whether or not novel combinations of foods (e.g., AB, CD, AD, CB) would cause an
      allergic reaction in Mr X. They were no more likely to indicate that AB or CD
      would cause an allergic reaction than AD or CB, but made their judgements more
      rapidly and with greater confidence on AB and CD trials than on AD and CB trials.
      These results (1) indicate that shared representations come to be addressed by
      the components of similar compounds (e.g., AX and BX) that have predicted the
      same outcome (an allergic reaction), and (2) are inconsistent with standard,
      associative theories of learning, but (3) are consistent with findings from
      nonhuman animals and with a connectionist interpretation of these findings.

PMID- 12791572
TI  - Latent inhibition of US signal value.
AB  - Three experiments with rats examined the effects of preexposure to an
      unconditioned stimulus (US; a single food pellet) on the subsequent ability of
      that US to effectively signal the delivery of three food pellets during a US-US
      conditioning procedure. In Experiment 1, latent inhibition (LI) rats showed
      attenuated conditioning, compared to control (C) rats, when a single food pellet,
      delivered 10 minutes into a session, was followed by three additional pellets. In
      preexposure, one pellet had been delivered 10 minutes into each session (in group
      LI), or placed into the magazine at the beginning of each session (in group C).
      Experiment 2 showed that this effect was evident when the conditions of
      preexposure matched those of conditioning for group C, and Experiment 3 showed
      that the difference between groups LI and C was not a product of context
      conditioning, or latent inhibition to the noise of the feeder in group LI.
      Implications of these results for theories of latent inhibition are considered.

PMID- 12791578
TI  - Low-dose vasopressin in the treatment of septic shock in sheep.
AB  - After induction of cecal perforation, 20 anesthetized sheep were randomized to be
      treated, when arterial blood pressure fell below 75 mm Hg, with vasopressin
      (fixed dose of 0.02 U/minute), norepinephrine (0.5-5 microg/kg/minute titrated to
      maintain mean arterial pressure between 75 and 85 mm Hg), vasopressin +
      norepinephrine (vasopressin at fixed dose 0.01 U/minute plus norepinephrine
      titrated as for norepinephrine only group), or no vasopressor (Ringer's lactate
      [control]). Mean arterial pressure was well maintained in all treatment groups.
      Superior mesenteric arterial blood flow was significantly lower in the
      vasopressin + norepinephrine group than in the vasopressin group. Vasopressin
      alone or combined with norepinephrine limited the increase in blood lactate
      concentration and ileal PCO2-gap compared with control and norepinephrine groups.
      Urine output was higher in the vasopressin group than in control and
      norepinephrine groups. Survival time was longer in the vasopressin (30 +/- 6
      hours) and vasopressin + norepinephrine (30 +/- 3 hours) groups than in the
      norepinephrine group (20 +/- 1 hours, p < 0.05) and in all treatment groups than
      in the control group (17 +/- 2 hours, p < 0.05). Tissue injury was less severe in
      the vasopressin and vasopressin + norepinephrine groups than in the others. In
      this clinically relevant model of septic shock due to peritonitis, vasopressin
      administration (alone or with norepinephrine) can prolong survival.

PMID- 12791579
TI  - Delaying decline in pulmonary function with physical activity: a 25-year follow
      up.
AB  - The importance of physical activity for health is well recognized, but little is
      known about the influence of physical activity on pulmonary function. We have
      examined whether physical activity could slow down the decline in pulmonary
      function among the southwestern rural Finnish cohort of the Seven Countries
      Study. Physical activity was estimated by kilometers walked, cycled, and skied
      daily. We had complete data for 429 men for 10 years, 275 men for 20 years, and
      186 men for 25 years. During the first 10 years, the decline in FEV was 9.8
      ml/year less among men in the highest tertile of baseline physical activity than
      in men in the lowest tertile. According to the mean physical activity over either
      20 or 25 years, men in the highest tertile also lost less pulmonary function (p =
      0.009 and p = 0.043, respectively). A similar beneficial effect was observed in
      all smoking categories. In mortality analysis, continued high physical activity
      and an increase in activity to high level were associated with lower mortality.
      In conclusion, results indicated that physical activity is associated with a
      slower decline in pulmonary function and with lower mortality, and thus, middle
      aged and older people should be encouraged to enjoy exercise.

PMID- 12791580
TI  - Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal
      functional trends.
AB  - Survival is linked to the histopathologic distinction between usual interstitial
      pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), the most commonly
      encountered fibrotic idiopathic interstitial pneumonia. We retrospectively
      compared the prognostic significance of histopathologic diagnoses, baseline
      pulmonary function indices, and serial trends in pulmonary function indices
      (diffusing capacity, FVC, FEV1, the recently defined composite physiologic index)
      at 6 and 12 months in 104 patients (UIP, n = 63; fibrotic NSIP, n = 41). Survival
      was lower in UIP than in fibrotic NSIP (p = 0.001) but not in patients with
      severe functional impairment; mortality during the first 2 years was linked
      solely to the severity of functional impairment at presentation. The composite
      physiologic index was the strongest determinant of outcome (p < 0.001). At 6
      months, serial diffusing capacity levels (p = 0.003) and histopathologic
      diagnosis (p = 0.002) were prognostically equivalent. At 12 months, serial
      pulmonary function trends were the only major prognostic determinant (p < 0.0005
      for all variables), with no independent significance associated with the
      distinction between UIP and fibrotic NSIP. We conclude that at 12 months, serial
      pulmonary function trends have considerable prognostic value in UIP and NSIP.
      Their histologic distinction provides no additional prognostic information when
      pulmonary function trends are clear cut or when functional impairment is severe.

PMID- 12791581
TI  - Prenatal cigarette smoke decreases lung cAMP and increases airway
      hyperresponsiveness.
AB  - Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily
      through maternal smoking, increases the risk for asthma in children; however, the
      mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes
      airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we
      examined the effects of in utero cigarette smoke exposure of Balb/c mice on
      airway responsiveness, as determined by Penh measurements. Animals exposed
      prenatally but not postnatally to cigarette smoke exhibited increased airway
      hyperresponsiveness after a single intratracheal injection of Aspergillus
      fumigatus extract. The increased airway hyperresponsiveness was not associated
      with increased leukocyte migration or mucous production in the lung but was
      causally related to decreased lung cyclic adenosine monophosphate levels,
      increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D
      (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung.
      Exposure of adult mice to cigarette smoke did not significantly alter airway
      responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase
      activity. These results suggest that prenatal exposure to cigarette smoke affects
      lung airway reactivity by modulating the lung cyclic adenosine monophosphate
      levels through changes in phosphodiesterase-4D activity, and these effects are
      independent of significant mucous production or leukocyte recruitment into the
      lung.

PMID- 12791582
TI  - Integrin alpha4beta1 regulates migration across basement membranes by lung
      fibroblasts: a role for phosphatase and tensin homologue deleted on chromosome
      10.
AB  - Idiopathic pulmonary fibrosis is a disease that is characterized by fibroblast
      accumulation and activation in the distal airspaces of the lung. We hypothesized
      that fibrotic lung fibroblasts migrate/invade across basement membranes by
      integrin-mediated mechanisms as a means of entering alveoli. We demonstrate that
      in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis,
      fibronectin signaling is both necessary and sufficient for basement membrane
      migration/invasion across basement membranes. This effect is mediated through the
      alpha5beta1 integrin because blockade of fibronectin-alpha5 integrin ligation
      attenuated this response. In contrast, ligation of alpha4beta1 integrin inhibits
      basement membrane invasion by normal lung fibroblasts but not by fibrotic lung
      fibroblasts. This phenotypic difference is not related to surface expression of
      the alpha4beta1 integrin, as demonstrated by flow cytometry. In normal lung
      fibroblasts but not in fibrotic lung fibroblasts, we show that ligation of
      alpha4beta1 integrin induces a significant increase in phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) activity. Fibrotic lung fibroblasts
      express constitutively less PTEN mRNA and protein as well as phosphatase activity
      in comparison to normal lung fibroblasts. Together, these data suggest that a
      loss of alpha4beta1 signaling via PTEN confers a migratory/invasive phenotype to
      fibrotic lung fibroblasts. Furthermore, this study implicates a loss of PTEN
      function in the pathophysiology of idiopathic pulmonary fibrosis.

PMID- 12791583
TI  - Further evidence for the role of genes on chromosome 2 and chromosome 5 in the
      inheritance of pulmonary function.
AB  - The spirometric measurements FEV1, FVC, and the ratio FEV1/FVC are used in the
      diagnosis of lung function disorders. Therefore, understanding the genetics
      underlying these spirometric measurements will increase our knowledge of the
      genetics of pulmonary function. FEV1 and FVC were measured on 264 members of 26
      Utah Genetic Reference pedigrees, originally collected for the Centre d'Etude du
      Polymorphisme Humain genetic mapping project. Using segregation analysis, we
      inferred major locus inheritance of the FEV1/FVC ratio, although we could not
      distinguish between a dominant or recessive mode of inheritance. No evidence of
      major locus inheritance was found for either FEV1 or FVC. Suggestive evidence of
      linkage for the ratio FEV1/FVC was found on chromosome 2 (heterogeneity lod =
      2.36, dominant model) and chromosome 5 (heterogeneity lod = 2.23, recessive
      model), replicating linkages from other studies. In addition, nonparametric
      variance component linkage analysis showed linkage of FEV1/FVC in both of these
      regions, providing further support to the results. No nonparametric lod scores
      over 1.5 were obtained for either FEV1 or FVC.

PMID- 12791584
TI  - Metabolic fate of yolk fatty acids in the developing king penguin embryo.
AB  - This study examines the metabolic fate of total and individual yolk fatty acids
      (FA) during the embryonic development of the king penguin, a seabird
      characterized by prolonged incubation (53 days) and hatching (3 days) periods,
      and a high n-3/n-6 polyunsaturated FA ratio in the egg. Of the approximately 15 g
      of total FA initially present in the egg lipid, 87% was transferred to the embryo
      by the time of hatching, the remaining 13% being present in the internalized yolk
      sac of the chick. During the whole incubation, 83% of the transferred FA was
      oxidized for energy, with only 17% incorporated into embryo lipids. Prehatching
      (days 0-49), the fat stores (triacylglycerol) accounted for 58% of the total FA
      incorporated into embryo lipid. During hatching (days 49-53), 40% of the FA of
      the fat stores was mobilized, the mobilization of individual FA being
      nonselective. At hatch, 53% of the arachidonic acid (20:4n-6) of the initial yolk
      had been incorporated into embryo lipid compared with only 15% of the total FA
      and 17-24% of the various n-3 polyunsaturated FA. Similarly, only 32% of the
      yolk's initial content of 20:4n-6 was oxidized for energy during development
      compared with 72% of the total FA and 58-66% of the n-3 polyunsaturated FA. The
      high partitioning of yolk FA toward oxidization and the intense mobilization of
      fat store FA during hatching most likely reflect the high energy cost of the long
      incubation and hatching periods of the king penguin. The preferential
      partitioning of 20:4n-6 into the structural lipid of the embryo in the face of
      its low content in the yolk may reflect the important roles of this FA in tissue
      function.

PMID- 12791585
TI  - Modulation of guinea pig intrinsic cardiac neurons by prostaglandins.
AB  - Activation of cardiac mast cells has been shown to alter parasympathetic neuronal
      function via the activation of histamine receptors. The present study examined
      the ability of prostaglandins to alter the activity of guinea pig intracardiac
      neurons. Intracellular voltage recordings from whole mounts of the cardiac plexus
      showed that antigen-mediated mast cell degranulation produces an attenuation of
      the afterhyperpolarization (AHP), which was prevented by the phospholipase A2
      inhibitor 5,8,11,14-eicosatetraynoic acid. Exogenous application of either PGD2
      or PGE2 produced a biphasic change in the membrane potential and an inhibition of
      both AHP amplitude and duration. Examination of prostanoid receptors using bath
      perfusions (1 microM PGE2 and PGD2), specific agonists (BW245C, sulprostone, and
      butaprost), and antagonists (AH6809 and SC19220) found evidence for both the PGE2
      specific EP2 and EP3 receptors, but not for EP1 or the PGD2-specific prostanoid
      (DP) receptors. Sulprostone was able to mimic the PGE2 responses in some cells,
      but not in all PGE2-sensitive cells. Butaprost was able to mimic the PG-induced
      hyperpolarization in some cells, but did not alter the AHP. Inhibition of
      specific potassium channels with either TEA, charybdotoxin, or apamin showed that
      neither TEA nor charybdotoxin could prevent the PGE2-induced AHP attenuation.
      Apamin alone inhibited AHP duration, with PGs having no further effect in these
      cells. These results demonstrate that guinea pig intracardiac neurons can be
      modulated by PG, most likely through either EP2, EP3, or potentially EP4
      receptors, and this response is due, at least in part, to a reduction in small
      conductance KCa currents.

PMID- 12791587
TI  - Differential mechanisms for regulation of the stress response across latitudinal
      gradients.
AB  - We examined plasticity of the stress response among three populations of the
      white-crowned sparrow (Zonotrichia leucophrys). These populations breed at
      different elevations and latitudes and thus have breeding seasons that differ
      markedly in length. We hypothesize that in populations where birds raise only one
      or rarely two broods in a season, the fitness costs of abandoning a nest are
      substantially larger than in closely related populations that raise up to three
      broods per season. Thus individuals with short breeding seasons should be less
      responsive to stressors and therefore less likely to abandon their young. In our
      study, baseline and handling-induced corticosterone levels were similar among
      populations, but corticosteroid-binding globulins differed, leading to a direct
      relationship between stress-induced free corticosteroid levels and length of
      breeding season. There were also population-specific differences in intracellular
      low-affinity (glucocorticoid-like) receptors in both liver and brain tissue.
      Although investigations of population-based differences in glucocorticoid
      secretion are common, this is the first study to demonstrate population-level
      differences in binding globulins. These differences could lead to dramatically
      different physiological and behavioral responses to stress.

PMID- 12791586
TI  - Increased H(2)O(2) counteracts the vasodilator and natriuretic effects of
      superoxide dismutation by tempol in renal medulla.
AB  - A membrane-permeable SOD mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl
      (tempol), has been used as an antioxidant to prevent hypertension. We recently
      found that this SOD mimetic could not prevent development of hypertension induced
      by inhibition of renal medullary SOD with diethyldithiocarbamic acid. The present
      study tested a hypothesis that increased H2O2 counteracts the effects of tempol
      on renal medullary blood flow (MBF) and Na+ excretion (UNaV), thereby restraining
      the antihypertensive effect of this SOD mimetic. By in vivo microdialysis and
      Amplex red H2O2 microassay, it was found that interstitial H2O2 levels in the
      renal cortex and medulla in anesthetized rats averaged 55.91 +/- 3.66 and 102.18
      +/- 5.16 nM, respectively. Renal medullary interstitial infusion of tempol (30
      micromol x min-1x kg-1) significantly increased medullary H2O2 levels by 46%, and
      coinfusion of catalase (10 mg x min-1x kg-1) completely abolished this increase.
      Functionally, removal of H2O2 by catalase enhanced the tempol-induced increase in
      MBF, urine flow, and UNaV by 28, 41, and 30%, respectively. Direct delivery of
      H2O2 by renal medullary interstitial infusion (7.5-30 nmol x min-1x kg-1)
      significantly decreased renal MBF, urine flow, and UNaV, and catalase reversed
      the effects of H2O2. We conclude that tempol produces a renal medullary
      vasodilator effect and results in diuresis and natriuresis. However, this SOD
      mimetic increases the formation of H2O2, which constricts medullary vessels and,
      thereby, counteracts its vasodilator actions. This counteracting effect of H2O2
      may limit the use of tempol as an antihypertensive agent under exaggerated
      oxidative stress in the kidney.

PMID- 12791588
TI  - Dynamics and contribution of mechanisms mediating renal blood flow
      autoregulation.
AB  - We investigated dynamic characteristics of renal blood flow (RBF) autoregulation
      and relative contribution of underlying mechanisms within the autoregulatory
      pressure range in rats. Renal arterial pressure (RAP) was reduced by suprarenal
      aortic constriction for 60 s and then rapidly released. Changes in renal vascular
      resistance (RVR) were assessed following rapid step reduction and RAP rise. In
      response to rise, RVR initially fell 5-10% and subsequently increased
      approximately 20%, reflecting 93% autoregulatory efficiency (AE). Within the
      initial 7-9 s, RVR rose to 55% of total response providing 37% AE, reaching
      maximum speed at 2.2 s. A secondary RVR increase began at 7-9 s and reached
      maximum speed at 10-15 s. Response times suggest that the initial RVR reflects
      the myogenic response and the secondary tubuloglomerular feedback (TGF). During
      TGF inhibition by furosemide, AE was 64%. The initial RVR rise was accelerated
      and enhanced, providing 49% AE, but it represented only 88% of total. The
      remaining 12% indicates a third regulatory component. The latter contributed up
      to 50% when the RAP increase began below the autoregulatory range. TGF
      augmentation by acetazolamide affected neither AE nor relative myogenic
      contribution. Diltiazem infusion markedly inhibited AE and the primary and
      secondary RVR increases but left a slow component. In response to RAP reduction,
      initial vasodilation constituted 73% of total response but was not affected by
      furosemide. The third component's contribution was 9%. Therefore, RBF
      autoregulation is primarily due to myogenic response and TGF, contributing 55%
      and 33-45% in response to RAP rise and 73% and 18-27% to RAP reduction. The data
      imply interaction between TGF and myogenic response affecting strength and speed
      of myogenic response during RAP rises. The data suggest a third regulatory system
      contributing <12% normally but up to 50% at low RAP; its nature awaits further
      investigation.

PMID- 12791589
TI  - Quantitative assessment of tyrosine nitration of manganese superoxide dismutase
      in angiotensin II-infused rat kidney.
AB  - Hypertension caused by angiotensin II is characterized by an increase in tissue
      oxidant stress as evidenced by increased quantities of reactive oxygen and
      nitrogen species. Manganese superoxide dismutase (MnSOD) is a key mitochondrial
      antioxidant enzyme that is inactivated in conditions of oxidant stress by
      reacting with peroxynitrite to form 3-nitrotyrosine in its active site. The
      increase in 3-nitrotyrosine content in MnSOD in the kidney of angiotensin II
      infused rats was assessed in this study by immunohistochemistry, Western
      blotting, immunoprecipitation, and HPLC with UV detection (HPLC-UV). MnSOD
      activity decreased approximately 50% in angiotensin II-infused rat kidneys (24 +/
      4.6 vs. 11 +/- 5.2 U/mg) without a change in protein expression.
      Immunohistochemical staining showed 3-nitrotyrosine predominantly in distal
      tubules and collecting duct cells in the angiotensin II-infused rat kidneys. By
      two-photon microscopy, 3-nitrotyrosine colocalized with MnSOD. Total 3
      nitrotyrosine content in kidney homogenates was increased in angiotensin II
      infused rat kidney [3.2 +/- 1.9 (sham treated) vs. 9.5 +/- 2.3 ng/mg protein by
      HPLC-UV detection]. With tracer amounts of tyrosine-nitrated recombinant MnSOD,
      the most sensitive technique to detect tyrosine nitration of MnSOD was
      immunoprecipitation from tissue with anti-MnSOD antibody, followed by detection
      of 3-nitrotyrosine by Western blotting or HPLC. By HPLC, 3-nitrotyrosine content
      of kidney MnSOD increased 13-fold after angiotensin II infusion, representing an
      increase from approximately one-twentieth to one-fifth of the total 3
      nitrotyrosine content in sham-treated and angiotensin II-infused rat kidney,
      respectively. Angiotensin II-induced hypertension is accompanied by increased
      tyrosine nitration of MnSOD, which, because it inactivates the enzyme, may
      contribute to increased oxidant stress in the kidney.

PMID- 12791590
TI  - Noninvasive remote ischemic preconditioning for global protection of skeletal
      muscle against infarction.
AB  - The aim of this study was to investigate the efficacy and mechanism of action of
      a noninvasive remote ischemic preconditioning (IPC) technique for the protection
      of multiple distant skeletal muscles against ischemic necrosis (infarction). It
      was observed in the pig that three cycles of 10-min occlusion and reperfusion in
      a hindlimb by tourniquet application reduced the infarction of latissimus dorsi
      (LD), gracilis (GC), and rectus abdominis (RA) muscle flaps by 55%, 60%, and 55%,
      respectively, compared with their corresponding control (n = 6, P < 0.01) when
      they were subsequently subjected to 4 h of ischemia and 48 h of reperfusion. This
      infarct-protective effect of remote IPC in LD muscle flaps was abolished by an
      intravenous bolus injection of the nonselective opioid receptor antagonist
      naloxone (3 mg/kg) 10 min before remote IPC and a continuous intravenous infusion
      (3 mg/kg) during remote IPC and by an intravenous bolus injection of the
      selective delta 1-opioid receptor antagonist 7-benzylidenealtrexone maleate (3
      mg/kg). However, this infarct-protective effect of remote IPC was not affected by
      an intravenous bolus injection of the ganglionic blocker hexamethonium chloride
      (20 mg/kg) or the nonspecific adenosine receptor antagonist 8-(p
      sulfophenyl)theophylline (10 mg/kg) or by a local intra-arterial injection of the
      adenosine1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (3 mg/muscle
      flap) given 10 min before remote IPC. It was also observed that this remote IPC
      of skeletal muscle against infarction was associated with a slower rate of muscle
      ATP depletion during the 4 h of sustained ischemia and a reduced muscle
      neutrophilic myeloperoxidase activity after 1.5 h of reperfusion. These
      observations led us to speculate that noninvasive remote IPC by brief cycles of
      occlusion and reperfusion in a pig hindlimb is effective in global protection of
      skeletal muscle against infarction. This infarct-protective effect is most likely
      triggered by the activation of opioid receptors in the skeletal muscle, and
      remote IPC is associated with an energy-sparing effect during sustained ischemia
      and attenuation of neutrophil accumulation during reperfusion.

PMID- 12791591
TI  - Identification of a CArG-independent region of the cysteine-rich protein 2
      promoter that directs expression in the developing vasculature.
AB  - Cysteine-rich protein (CRP)2 is a member of the LIM-only CRP family that is
      expressed in vascular smooth muscle cells (VSMC). To gain insight into the
      transcription of CSRP2 (gene name for CRP2) in VSMC, we analyzed the 5'-flanking
      sequence of the CSRP2 gene. We showed previously that 4,855 bp of the 5'-flanking
      sequence of the CSRP2 gene directed lacZ reporter gene expression, primarily in
      the VSMC of transgenic mice. To further define the regulatory sequences important
      for CSRP2 expression in VSMC, a series of promoter constructs containing
      deletions of the 5'-flanking sequence upstream of a nuclear-localized lacZ
      reporter gene were generated and analyzed. Similar to that observed in the 
      4855CSRP2-lacZ mice, beta-galactosidase reporter activity was detected in the
      developing great vessels, aorta, intersegmental arteries, umbilical vessels,
      endocardial cushions, and neural tube in the -3513-, -2663-, -795-, and -664CSRP2
      lacZ lines. However, an internal deletion of bp -573 to -550 abolished the
      vascular, but not the neural tube, staining. Interestingly, no CArG box
      [CC(A/T)6GG] was present in the -795-bp fragment. Cotransfection experiments
      showed that dominant-negative serum response factor (SRF) did not repress CSRP2
      promoter activity, which was different from the repressive effect of dominant
      negative SRF on the SM22 alpha promoter. Our data suggest the presence of a VSMC
      specific element(s) within bp -573 to -550 of the CSRP2 5'-flanking sequence;
      however, in contrast to many other smooth muscle genes, transcriptional
      regulation of the CSRP2 gene is not dependent on SRF.

PMID- 12791592
TI  - Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart
      failure.
AB  - Human urotensin-II (hU-II) is the most potent endogenous cardiostimulant
      identified to date. We therefore determined whether hU-II has a possible
      pathological role by investigating its levels in patients with congestive heart
      failure (CHF). Blood samples were obtained from the aortic root, femoral artery,
      femoral vein, and pulmonary artery from CHF patients undergoing cardiac
      catheterization and the aortic root from patients undergoing investigative
      angiography for chest pain who were not in heart failure. Immunoreactive hU-II
      (hU-II-ir) levels were determined with radioimmunoassay. hU-II-ir was elevated in
      the aortic root of CHF patients (230.9 +/- 68.7 pg/ml, n = 21; P < 0.001) vs.
      patients with nonfailing hearts (22.7 +/- 6.1 pg/ml, n = 18). This increase was
      attributed to cardiopulmonary production of hU-II-ir because levels were lower in
      the pulmonary artery (38.2 +/- 6.1 pg/ml, n = 21; P < 0.001) than in the aortic
      root. hU-II-ir was elevated in the aortic root of CHF patients with nonischemic
      cardiomyopathy (142.1 +/- 51.5 pg/ml, n = 10; P < 0.05) vs. patients with
      nonfailing hearts without coronary artery disease (27.3 +/- 12.4 pg/ml, n = 7)
      and CHF patients with ischemic cardiomyopathy (311.6 +/- 120.4 pg/ml, n = 11; P <
      0.001) vs. patients with nonfailing hearts and coronary artery disease (19.8 +/-
      6.6 pg/ml, n = 11). hU-II-ir was significantly higher in the aortic root than in
      the pulmonary artery and femoral vein, with a nonsignificant trend for higher
      levels in the aortic root than in the femoral artery. The findings indicated that
      hU-II-ir is elevated in the aortic root of CHF patients and that hU-II-ir is
      cleared at least in part from the microcirculation.

PMID- 12791593
TI  - Imaging hemoglobin oxygen saturation in sickle cell disease patients using
      noninvasive visible reflectance hyperspectral techniques: effects of nitric
      oxide.
AB  - Sickle cell disease is characterized by microvascular occlusion and hemolytic
      anemia, factors that impair tissue oxygen delivery. We use visible reflectance
      hyperspectral imaging to quantitate skin tissue hemoglobin oxygen saturation
      (HbO2) and to determine whether changes in blood flow during nitric oxide (NO)
      stimulation or gas administration (therapies proposed for this disease) improve
      skin tissue oxygen saturation in five patients with sickle cell disease. Compared
      with six healthy African-American subjects, sickle cell patients exhibited higher
      forearm blood flows (7.4 +/- 1.8 vs. 3.2 +/- 0.4 ml.min-1.100 ml tissue-1, P =
      0.037) but significantly reduced percentages of skin HbO2 (61.0 +/- 0.2 vs. 77.5
      +/- 0.2%, P < 0.001). Administration of acetylcholine to patients increased blood
      flow by 15.1 +/- 3.8 ml.min-1.100 ml tissue-1 and the percentage of skin HbO2 by
      4.1 +/- 0.3% (P = 0.02, P < 0.001, respectively, from baseline values). Sodium
      nitroprusside, a direct NO donor, increased blood flow by 3.9 +/- 1.1 ml/min and
      the percentage of skin HbO2 by 2.9 +/- 0.3% (P = 0.02, P < 0.001, respectively).
      NO inhalation had no effect on forearm blood flow, yet increased the percentage
      of skin HbO2 by 2.3 +/- 0.3% (P < 0.001). Percentages of skin HbO2 were
      exponentially related to blood flow (R = 0.97, P < 0.001), indicating a limit to
      skin tissue oxygen saturation at high blood flows. Thus, for acetylcholine
      infusion leading to blood flows sevenfold greater than those of healthy resting
      African-American subjects, patients still exhibited lower percentages of skin
      HbO2 (65.2 +/- 0.2 vs. 77.5 +/- 0.2%, P < 0.001). Visible reflectance
      hyperspectral imaging demonstrates that either the stimulation or the
      administration of NO pharmacologically or by gas inhalation improves, but does
      not normalize, skin tissue oxygen saturation in patients with sickle cell
      disease.

PMID- 12791594
TI  - Age and attenuation of exercise-induced myocardial HSP72 accumulation.
AB  - Overexpression of heat shock protein (HSP)72 is associated with cardioprotection.
      Hyperthermia-induced HSP72 overexpression is attenuated with senescence. While
      exercise also increases myocardial HSP72 in young animals, it is unknown whether
      this effect is attenuated with aging. Therefore, we investigated the effect of
      aging on exercise-induced myocardial heat shock factor (HSF)-1 activation and
      HSP72 expression. Male Fischer-344 rats (6 or 24 mo) were randomized to control,
      exercise, and hyperthermic groups. Exercise consisted of 2 days of treadmill
      running (60 min/day, approximately 75% maximal oxygen consumption). Hyperthermia,
      15 min at approximately 41 degrees C (colonic temperature), was achieved using a
      temperature-controlled heating blanket. Analyses included Western blotting for
      myocardial HSP72 and HSF-1, electromobility shift assays for HSF-1 activation,
      and Northern blotting for HSP72 mRNA. Exercise and hyperthermia increased (P <
      0.05) myocardial HSP72 in both young (>3.5- and 2.5-fold, respectively) and aged
      (>3- and 1.5-fold, respectively) animals. Both exercise and hyperthermic
      induction of HSP72 was attenuated with age. Myocardial HSF-1 protein, HSF-1
      activation, and HSP72 mRNA did not differ with age. These data demonstrate that
      aging is associated with diminished exercise-induced myocardial HSP72 expression.
      Mechanisms other than HSF-1 activation and transcription of HSP72 mRNA are
      responsible for this age-related impairment.

PMID- 12791595
TI  - Characterization of fibrillatory rhythms by ensemble vector directional analysis.
AB  - Recent studies have demonstrated that fibrillatory rhythms are not random
      phenomena but have definable patterns. However, standard mapping techniques may
      have limitations in their ability to identify the organization of fibrillation.
      The purpose of this study was to develop and apply a method, "ensemble vector
      mapping," for characterizing the spatiotemporal organization of fibrillation.
      Ventricular fibrillation was induced by burst pacing in normal mongrel dogs. In a
      separate protocol, atrial fibrillation was induced by epicardial aconitine
      application. Epicardial electrograms were recorded from a 112-electrode plaque
      array using a computerized mapping system. Vectors were created by summing
      orthogonal bipolar electrograms. The magnitude of the vectors was transformed
      using a logarithmic function, integrated over time, and normalized for local
      electrogram amplitude to produce an "ensemble vector" index whose magnitude is
      high when beat-to-beat activation direction is consistent and low when activation
      direction is variable. The mean index was 137 +/- 36 mV/s during ventricular
      pacing at a cycle length of 300 ms but only 39 +/- 23 mV/s during ventricular
      fibrillation (P < 0.001). The ensemble vector index was also lower during atrial
      fibrillation (60 +/- 54 mV/s) than during atrial pacing (115 +/- 27 mV/s, P <
      0.01 vs. atrial fibrillation) but not as low as during ventricular fibrillation
      (P < 0.05, atrial vs. ventricular fibrillation). The index was also capable of
      distinguishing atrial tachycardia from atrial fibrillation. Ensemble vector
      mapping produces an objective assessment of the consistency of myocardial
      activation during fibrillation. The consistency of activation direction differs
      in different models of fibrillation and is higher during atrial than ventricular
      fibrillation. This technique has the potential to rapidly characterize repetitive
      activation patterns in fibrillatory rhythms and may help distinguish among
      different characteristics of fibrillatory rhythms.

PMID- 12791596
TI  - Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced
      liver fibrosis in rats.
AB  - Accumulation of hydrophobic bile acids during cholestasis leads to generation of
      oxygen free radicals in the liver. Accordingly, this study investigated whether
      polyphenols from green tea Camellia sinenesis, which are potent free radical
      scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were
      fed a standard chow or a diet containing 0.1% polyphenolic extracts from C.
      sinenesis starting 3 days before bile duct ligation. After bile duct ligation,
      serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control
      diet. Focal necrosis and bile duct proliferation were also observed after 1-2
      days, and fibrosis developed 2-3 wk after bile duct ligation. Additionally,
      procollagen-alpha1(I) mRNA increased 30-fold 3 wk after bile duct ligation,
      accompanied by increased expression of alpha-smooth muscle actin and transforming
      growth factor-beta and the accumulation of 4-hydroxynenonal, an end product of
      lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct
      ligation-dependent changes by 45-73%. Together, the results indicate that
      cholestasis due to bile duct ligation causes liver injury by mechanisms involving
      oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and
      prevent activation of stellate cells, thereby minimizing liver fibrosis.

PMID- 12791597
TI  - Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions
      of dorsal vagal complex to inhibit emesis in ferrets.
AB  - The aim of this study was to investigate the efficacy, receptor specificity, and
      site of action of Delta9-tetrahydrocannabinol (THC) as an antiemetic in the
      ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of
      cisplatin. The ED50 for retching was approximately 0.1 mg/kg and for vomiting was
      0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg
      ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5
      mg/kg ip) was ineffective. THC applied to the surface of the brain stem was
      sufficient to inhibit emesis induced by intragastric hypertonic saline. The site
      of action of THC in the brain stem was further assessed using Fos
      immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor
      nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the
      solitary tract (NTS), but not other subnuclei of the NTS, was significantly
      reduced by THC rostral to obex. At the level of the obex, THC reduced Fos
      expression in the area postrema and the dorsal subnucleus of the NTS. The highest
      density of CB1 receptor immunoreactivity was found in the DMNX and the medial
      subnucleus of the NTS. Lower densities were observed in the area postrema and
      dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of
      staining in the commissural subnucleus of the NTS. These results show that THC
      selectively acts at CB1 receptors to reduce neuronal activation in response to
      emetic stimuli in specific regions of the dorsal vagal complex.

PMID- 12791598
TI  - Mathematical description of regenerative potentials recorded from circular smooth
      muscle of guinea pig antrum.
AB  - Regenerative potentials evoked by intracellular current injection in single
      bundles of circular smooth muscle taken from guinea pig antrum have the
      characteristics of the secondary regenerative component of the slow wave
      occurring in the same muscle layer. Such regenerative depolarizations might
      result from a mechanism that responds to membrane polarization with a delayed
      increase in the rate of production of unitary potentials detected in this tissue.
      To test this possibility, a two-stage reaction leading to the formation of an
      intracellular messenger was proposed. The first forward reaction was voltage
      dependent, in the manner described by the Hodgkin-Huxley transient Na conductance
      formalism, allowing simulation of anode break excitation, stimulus threshold
      strength-duration characteristics, and refractory behavior. A conventional dose
      effect relationship was proposed to describe the dependence of the mean rate of
      discharge of unitary potentials on messenger concentration. Unitary potentials
      were modeled as unitary membrane conductance modulations with an empirically
      derived amplitude distribution and Poisson-distributed intervals. The model
      reproduces a range of spontaneous and evoked membrane potential changes
      characteristic of antral circular muscle bundles.

PMID- 12791599
TI  - Apoptosis is a major mechanism of deoxycholate-induced gastric mucosal cell
      death.
AB  - This study was undertaken to determine whether necrosis or apoptosis was the
      predominant mechanism responsible for gastric mucosal cellular death using the
      cell line known as AGS cells. Cells were exposed to various concentrations of
      deoxycholate (DC; 50-500 muM) for periods ranging from 30 min to 24 h. Lactic
      dehydrogenase (LDH) activity was used as a marker for necrotic cell death,
      whereas apoptosis was characterized by 4',6-diamidino-2 phenylindole staining,
      DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end
      labeling assay and DNA-histone-associated complex formation. When cells were
      bathed in Hank's balanced salt solution, DC-induced necrosis was the predominant
      mechanism of cell death. In contrast, when cells were bathed in Ham's F-12
      solution (a more physiologically relevant medium), no evidence of cytotoxicity
      (by LDH assay) was discernible when cells were exposed to DC (50-300 muM) for
      periods as long as 8 h; instead, clear evidence of apoptosis was noted that was
      time and dose dependent. When cells were exposed for 24 h to these DC
      concentrations, cytotoxicity was also present, indicating necrosis as well.
      Furthermore, acidification of the ambient environment also evoked a necrotic
      response when exposed to DC. We demonstrated that apoptosis induced by DC shows
      early activation of caspase-3 that is dependent on both receptor and
      mitochondrial pathways. Our results indicate that physiological concentrations of
      DC (50-300 muM) primarily induce cellular death through an apoptotic process.
      Only after prolonged exposure to DC or acidification of the bathing solution does
      necrosis also occur.

PMID- 12791600
TI  - Transforming growth factor-beta1 downregulation of Smad1 gene expression in rat
      hepatic stellate cells.
AB  - Smads are intracellular signaling molecules of the transforming growth factor
      beta (TGF-beta) superfamily that play an important role in the activation of
      hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of
      Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat
      HSCs to investigate the expression and regulation of the Smad1 gene, which is a
      bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the
      expression and phosphorylation of Smad1 are increased during the activation of
      HSCs. Moreover, TGF-beta significantly inhibits Smad1 gene expression in HSCs in
      a time- and dose-dependent manner. Furthermore, although both TGF-beta1 and BMP2
      stimulate the activation of HSCs, they have different effects on HSC
      proliferation. In conclusion, Smad1 expression and phosphorylation are increased
      during the activation of HSCs and TGF-beta1 significantly inhibits the expression
      of the Smad1 gene.

PMID- 12791601
TI  - FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal
      mineralization.
AB  - There is evidence for a hormone/enzyme/extracellular matrix protein cascade
      involving fibroblastic growth factor 23 (FGF23), a phosphate-regulating gene with
      homologies to endopeptidases on the X chromosome (PHEX), and a matrix
      extracellular phosphoglycoprotein (MEPE) that regulates systemic phosphate
      homeostasis and mineralization. Genetic studies of autosomal dominant
      hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH) identified
      the phosphaturic hormone FGF23 and the membrane metalloprotease PHEX, and
      investigations of tumor-induced osteomalacia (TIO) discovered the extracellular
      matrix protein MEPE. Similarities between ADHR, XLH, and TIO suggest a model to
      explain the common pathogenesis of renal phosphate wasting and defective
      mineralization in these disorders. In this model, increments in FGF23 and MEPE,
      respectively, cause renal phosphate wasting and intrinsic mineralization
      abnormalities. FGF23 elevations in ADHR are due to mutations of FGF23 that block
      its degradation, in XLH from indirect actions of inactivating mutations of PHEX
      to modify the expression and/or degradation of FGF23 and MEPE, and in TIO because
      of increased production of FGF23 and MEPE. Although this model is attractive,
      several aspects need to be validated. First, the enzymes responsible for
      metabolizing FGF23 and MEPE need to be established. Second, the physiologically
      relevant PHEX substrates and the mechanisms whereby PHEX controls FGF23 and MEPE
      metabolism need to be elucidated. Finally, additional studies are required to
      establish the molecular mechanisms of FGF23 and MEPE actions on kidney and bone,
      as well as to confirm the role of these and other potential "phosphatonins," such
      as frizzled related protein-4, in the pathogenesis of the renal and skeletal
      phenotypes in XLH and TIO. Unraveling the components of this
      hormone/enzyme/extracellular matrix pathway will not only lead to a better
      understanding of phosphate homeostasis and mineralization but may also improve
      the diagnosis and treatment of hypo- and hyperphosphatemic disorders.

PMID- 12791602
TI  - Effects of fatty acids on hepatic amino acid catabolism and fibrinogen synthesis
      in young healthy volunteers.
AB  - Increased synthesis rate of fibrinogen, an independent risk factor for
      cardiovascular disease, was recently reported in obese insulin-resistant female
      adolescents with chronic elevated nonesterified fatty acids (NEFA). It is unknown
      whether a short-term change of NEFA concentrations controls hepatic fibrinogen
      synthesis. Therefore, 10 healthy male volunteers (24.5 +/- 3.3 yr, body mass
      index 23.5 +/- 2.9 kg/m2) were investigated in random order under basal and
      elevated NEFA for 8 h. Leucine metabolism, the fractional synthesis rates (FSR)
      of plasma fibrinogen, and endogenous urea production rates were measured during
      primed, continuous infusion of [1-13C]leucine and [15N2]urea, respectively.
      Plasma alpha-[13C]ketoisocaproic acid and [15N2]urea enrichment values were
      measured with GC-MS. Plasma fibrinogen was isolated with the beta-alanine method,
      and fibrinogen-related [13C]leucine enrichment was analyzed by GC-CIRMS.
      Lipofundin infusion and subcutaneous heparin tripled NEFA and triglycerides in
      the tests. Plasma glucose, circulating insulin, human C-peptide, and plasma
      glucagon were not changed by the study procedure. Fibrinogen FSR were
      significantly lower in tests with NEFA elevation (18.44 +/- 4.67%) than in
      control tests (21.48 +/- 4.32%; P < 0.05). Plasma fibrinogen concentrations
      measured were not significantly different (NEFA test subjects: 1.85 +/- 0.33,
      controls: 1.97 +/- 0.54 g/l). Parameters of leucine metabolism, such as leucine
      rate of appearance, leucine oxidation, and nonoxidative leucine disposal, were
      not influenced by NEFA elevation, and endogenous urea production remained
      unchanged. NEFA contributes to short-term regulation of fibrinogen FSR in healthy
      volunteers under unchanged hormonal status, leucine metabolism, and overall amino
      acid catabolism. Its contribution might be of relevance at least after fat-rich
      meals, counteracting by reduction of FSR the blood viscosity increase implied by
      hyperlipidemia.

PMID- 12791603
TI  - Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake
      in response to insulin.
AB  - We examined the effects of inhibiting nitric oxide synthase with Nomega-nitro-l
      arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular
      recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in
      vivo in the rat. We used two independent methods to measure microvascular
      perfusion. In one group of animals, microvascular recruitment was measured using
      the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second
      group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was
      measured by arterial-venous concentration differences after 2 h of insulin
      infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX
      metabolism. Insulin (10 mU.min-1.kg-1) significantly increased hindlimb total
      blood flow (0.69 +/- 0.02 to 1.22 +/- 0.11 ml/min, P < 0.05), glucose uptake
      (0.27 +/- 0.05 to 0.95 +/- 0.08 micromol/min, P < 0.05), 1-MX uptake (5.0 +/- 0.5
      to 8.5 +/- 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume
      measured by CEU (10.0 +/- 1.6 to 15.0 +/- 1.2 video intensity units, P < 0.05).
      Addition of l-NAME to insulin completely blocked the effect of insulin on both
      total limb flow and microvascular recruitment (measured using either 1-MX or CEU)
      and blunted glucose uptake by 40% (P < 0.05). We conclude that insulin
      specifically recruits flow to the microvasculture in skeletal muscle via a nitric
      oxide-dependent pathway and that this may be important to insulin's overall
      action to regulate glucose disposal.

PMID- 12791604
TI  - Sex-specific p38 MAP kinase activation following trauma-hemorrhage: involvement
      of testosterone and estradiol.
AB  - Although immune functions are markedly depressed in males and not in proestrous
      females following trauma-hemorrhage (T-H), the mechanisms responsible for the
      divergent responses remain unknown. Because sex steroids modulate the activation
      of p38, our aim was to determine whether differences in the activation of p38 by
      phosphorylation (p38-P) might contribute to the sex-dimorphic immune response
      following T-H. The effects of testosterone and estradiol on the activation of p38
      were also examined. Intact male mice (C3H/HeN), castrated males treated with
      vehicle, 5alpha-dihydrotestosterone (DHT), or 17beta-estradiol, and proestrous
      females were subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock
      (35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. At 2 h
      thereafter, splenic (SMphi) and peritoneal macrophages (PMphi) were harvested and
      cultured (with 10 microg/ml LPS), and Western blot analysis was carried out for
      quantification of p38 and p38-P. Sex, testosterone and estradiol plasma levels,
      and T-H did not alter the constitutive expression of p38 in SMphi and PMphi. In
      contrast, the activated form of p38 (p38-P) was markedly increased in SMphi and
      PMphi from female shams compared with male shams. Moreover, the phosphorylation
      of p38-P increased in males after T-H, whereas it decreased in females under
      those conditions. Castration before T-H prevented the increase in p38-P in males.
      Castrated animals treated with DHT displayed increased p38-P following T-H,
      whereas 17beta-estradiol had no effect on p38-P in castrated mice. Thus 1) sex
      influences the activation of p38 MAP kinase, 2) DHT is responsible for the
      increased activation of p38 in male mice, and 3) this sex-specific activation of
      p38 might be responsible for the sexually dimorphic immune response following T
      H.

PMID- 12791605
TI  - Myogenic and nonmyogenic cells differentially express proteinases, Hsc/Hsp70, and
      BAG-1 during skeletal muscle regeneration.
AB  - Skeletal muscle has a remarkable capacity to regenerate after injury. To
      determine whether changes in the expression of proteinases, 73-kDa constitutive
      heat shock cognate protein (Hsc70) and stress-inducible 72-kDa heat shock protein
      (Hsp70) (Hsc/Hsp70), and Bcl-2-associated gene product-1 (BAG-1) contribute to
      the remodeling response of muscle tissue, tibialis anterior muscles of male
      Sprague-Dawley rats were injected with 0.75% bupivacaine and removed at 3, 5, 7,
      10, 14, 21, or 35 days postinjection (n = 5-7/group). The immunohistochemical
      analysis of desmin, alpha-actin, and developmental/neonatal myosin heavy chain
      expressions indicated the presence of myoblasts (days 3-7), inflammatory cells
      (days 3-7), degenerating myofibers (days 3-7), regenerating myofibers (days 5
      10), and growing mature myofibers (days 10-21) in regenerating muscles. Our
      biochemical analysis documented profound adaptations in proteolytic metabolism
      characterized by significant increases in the enzyme activities of matrix
      metalloproteinases 2 and 9 and plasminogen activators (days 3-14), calpains 1 and
      2 (days 3-7), cathepsins B and L(days 3-10), and proteasome (days 3-14).
      Proteasome activity was strongly correlated with proliferating cell nuclear
      antigen protein level, suggesting that proteasome played a key role in myoblast
      proliferation. The expression pattern of BAG-1, a regulatory cofactor of
      Hsc/Hsp70 at the interface between protein folding and proteasomal proteolysis,
      did not corroborate the changes in proteasome enzyme activity, suggesting that
      BAG-1 may promote other functions, such as the folding capacity of Hsc/Hsp70.
      Altogether, the diversity of functions attributed to proteinases in the present
      study was strongly supported by the relative changes in the proportion of
      myogenic and nonmyogenic cells over the time course of regeneration.

PMID- 12791606
TI  - The reluctance of physicians to admit that chronic disease may be due to faulty
      diet. 1953.

PMID- 12791607
TI  - The whole is greater than the weighted average of its parts.

PMID- 12791608
TI  - Rapid weight gain during infancy as a predictor of adult obesity.

PMID- 12791609
TI  - Riboflavin (vitamin B-2) and health.
AB  - Riboflavin is unique among the water-soluble vitamins in that milk and dairy
      products make the greatest contribution to its intake in Western diets. Meat and
      fish are also good sources of riboflavin, and certain fruit and vegetables,
      especially dark-green vegetables, contain reasonably high concentrations.
      Biochemical signs of depletion arise within only a few days of dietary
      deprivation. Poor riboflavin status in Western countries seems to be of most
      concern for the elderly and adolescents, despite the diversity of riboflavin-rich
      foods available. However, discrepancies between dietary intake data and
      biochemical data suggest either that requirements are higher than hitherto
      thought or that biochemical thresholds for deficiency are inappropriate. This
      article reviews current evidence that diets low in riboflavin present specific
      health risks. There is reasonably good evidence that poor riboflavin status
      interferes with iron handling and contributes to the etiology of anemia when iron
      intakes are low. Various mechanisms for this have been proposed, including
      effects on the gastrointestinal tract that might compromise the handling of other
      nutrients. Riboflavin deficiency has been implicated as a risk factor for cancer,
      although this has not been satisfactorily established in humans. Current interest
      is focused on the role that riboflavin plays in determining circulating
      concentrations of homocysteine, a risk factor for cardiovascular disease. Other
      mechanisms have been proposed for a protective role of riboflavin in ischemia
      reperfusion injury; this requires further study. Riboflavin deficiency may exert
      some of its effects by reducing the metabolism of other B vitamins, notably
      folate and vitamin B-6.

PMID- 12791610
TI  - Regional body composition in adolescents with anorexia nervosa and changes with
      weight recovery.
AB  - BACKGROUND: Studies of regional fat distribution in adults with anorexia nervosa
      (AN) have shown decreased extremity fat at baseline and increased trunk fat with
      weight recovery, resulting in truncal adiposity. Little is known about fat
      distribution in adolescents with AN, especially with weight recovery. OBJECTIVE:
      We sought to determine whether regional fat distribution in adolescents with AN
      is comparable with that in healthy adolescents and whether weight recovery
      results in increased trunk fat and truncal adiposity. DESIGN: In 21 adolescent
      girls with AN and 21 control subjects matched for age and pubertal stage, we
      measured body-composition variables with dual-energy X-ray absorptiometry at
      baseline, 6 mo, and 12 mo. Weight recovery was defined as a > or = 10% increase
      in body mass index. RESULTS: At baseline, the girls with AN had a lower
      percentage of trunk fat than did the control subjects, whereas the percentage of
      extremity fat was not significantly different between the groups. Weight recovery
      in 13 subjects with AN resulted in an increased percentage of trunk fat and an
      increased ratio of trunk fat to extremity fat; however, this ratio did not exceed
      that of control subjects. CONCLUSIONS: In adolescents with AN, trunk fat rather
      than extremity fat is reduced. Weight recovery is associated with increased trunk
      fat and an increased ratio of trunk fat to extremity fat. In contrast with
      previous findings in adults, this most likely represents normalization of fat
      distribution rather than development of truncal adiposity.

PMID- 12791611
TI  - Influence of distribution of lean body mass on resting metabolic rate after
      weight loss and weight regain: comparison of responses in white and black women.
AB  - BACKGROUND: Little is known about the effect of weight change on regional lean
      body mass (LBM) distribution or on racial differences in resting metabolic rate
      (RMR). OBJECTIVE: The study compared total and regional LBM patterns in white and
      black women after weight loss and regain and assessed the influence of regional
      LBM on variances in RMR. DESIGN: Eighteen white and 22 black women who did not
      differ in age, weight, and height were studied 3 times: in the overweight state,
      after weight reduction to the normal-weight state, and after 1 y without
      intervention. Total and regional lean and fat masses were assessed by dual-energy
      X-ray absorptiometry. RESULTS: White and black women did not differ significantly
      in mean (+/- SD) weight loss (13.4 +/- 3.6 and 12.7 +/- 3.2 kg, respectively) and
      regain (6.1 +/- 5.5 and 6.4 +/- 5.4 kg, respectively). Black subjects had
      significantly less trunk LBM and significantly more limb LBM at each time point
      (P < 0.05). In both races, weight regain was associated with significant
      increases in limb LBM (P < 0.05) but not in trunk LBM (P = 0.21). RMR, adjusted
      for total LBM and fat mass, was significantly higher in white women after weight
      loss (P < 0.01) and regain (P < 0.01). However, no racial difference was found
      when RMR was adjusted for LBM distribution. CONCLUSIONS: In both races, trunk LBM
      decreased with weight loss and remained lower, despite significant weight regain,
      which potentially reflected decreased organ mass. Regional LBM distribution
      explained the racial difference in RMR.

PMID- 12791612
TI  - Rapid weight gain during infancy and obesity in young adulthood in a cohort of
      African Americans.
AB  - BACKGROUND: Obesity is increasing in the United States. Evidence-based prevention
      is a public health priority and should target well-defined risk factors and
      critical periods. OBJECTIVE: We tested the hypothesis that rapid weight gain
      during early infancy is associated with obesity in African American young adults,
      a group at increased risk of obesity. DESIGN: A cohort of 300 African Americans
      born at full term was followed from birth to 20 y of age. A pattern of rapid
      weight gain was defined as an increase in weight-for-age > or = 1 SD between
      birth and 4 mo. RESULTS: About 29% of subjects had a pattern of rapid weight gain
      during infancy; 8% were obese [body mass index (in kg/m(2)) > or = 30] at age 20
      y. One-third of the obesity at age 20 y could be attributed to rapid weight gain
      in the first 4 mo of life. After adjustment for confounding factors, subjects
      with rapid weight gain during early infancy were more likely to become obese at
      age 20 y (odds ratio = 5.22; 95% CI: 1.55, 17.6; P = 0.008). The results were
      confirmed by using a combination of body mass index and skinfold thickness (odds
      ratio = 6.72; 95% CI: 1.93, 23.4; P = 0.003). CONCLUSIONS: The results of the
      present study provide evidence that a pattern of rapid weight gain during early
      infancy is associated with obesity not only in childhood but also in young
      adulthood. We propose that early infancy constitutes a critical period for the
      development of obesity. Mechanisms of action and prevention strategies require
      further investigation.

PMID- 12791613
TI  - Serum lipid response to the graduated enrichment of a Step I diet with almonds: a
      randomized feeding trial.
AB  - BACKGROUND: Frequent consumption of nuts may lower the risk of cardiovascular
      disease by favorably altering serum lipid and lipoprotein concentrations.
      OBJECTIVE: We compared the effects of 2 amounts of almond intake with those of a
      National Cholesterol Education Program Step I diet on serum lipids, lipoproteins,
      apolipoproteins, and glucose in healthy and mildly hypercholesterolemic adults.
      DESIGN: In a randomized crossover design, 25 healthy subjects (14 men, 11 women)
      with a mean (+/- SD) age of 41 +/- 13 y were fed 3 isoenergetic diets for 4 wk
      each after being fed a 2-wk run-in diet (containing 34% of energy from fat). The
      experimental diets included a Step I diet, a low-almond diet, and a high-almond
      diet, in which almonds contributed 0%, 10%, and 20% of total energy,
      respectively. RESULTS: Inverse relations were observed between the percentage of
      energy in the diet from almonds and the subject's total cholesterol (P value for
      trend < 0.001), LDL-cholesterol (P < 0.001), and apolipoprotein B (P < 0.001)
      concentrations and the ratios of LDL to HDL cholesterol (P < 0.001) and of
      apolipoprotein B to apolipoprotein A (P < 0.001). Compared with the Step I diet,
      the high-almond diet reduced total cholesterol (0.24 mmol/L or 4.4%; P = 0.001),
      LDL cholesterol (0.26 mmol/L or 7.0%; P < 0.001), and apolipoprotein B (6.6 mg/dL
      or 6.6%; P < 0.001); increased HDL cholesterol (0.02 mmol/L or 1.7%; P = 0.08);
      and decreased the ratio of LDL to HDL cholesterol (8.8%; P < 0.001). CONCLUSIONS:
      Isoenergetic incorporation of approximately 68 g of almonds (20% of energy) into
      an 8368-kJ (2000-kcal) Step I diet markedly improved the serum lipid profile of
      healthy and mildly hypercholesterolemic adults. Total and LDL-cholesterol
      concentrations declined with progressively higher intakes of almonds, which
      suggests a dose-response relation.

PMID- 12791614
TI  - Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared
      with phytosterol-depleted wheat germ.
AB  - BACKGROUND: Low-fat vegetable foods contain phytosterols, but it is not known
      whether they are in biologically active forms or whether their concentrations are
      high enough to reduce cholesterol absorption and favorably affect lipid
      metabolism. OBJECTIVE: The objective was to establish whether the selective
      removal of phytosterols from wheat germ would increase the cholesterol absorption
      measured from test meals composed of wheat germ muffins. DESIGN: Wheat germ,
      which has a high content of phytosterols relative to total fat, was chosen as a
      low-fat test food. Cholesterol absorption was measured 3 times in 10 subjects.
      Each test meal was a muffin containing 30 mg heptadeuterated cholesterol tracer
      and, in random order, 80 g original wheat germ containing 328 mg phytosterols,
      wheat germ from which phytosterols had been selectively extracted, or extracted
      wheat germ reconstituted with purified phytosterols. Changes in cholesterol
      absorption were monitored by the measurement of tracer enrichment of plasma
      cholesterol 4 and 5 d after each meal with the use of negative ion mass
      spectrometry. RESULTS: Tracer enrichment of plasma cholesterol was 42.8% higher
      after consumption of phytosterol-free wheat germ than after that of the original
      wheat germ (0.415 +/- 0.035 compared with 0.291 +/- 0.024 micro mol tracer/mmol
      cholesterol; P < 0.01). Tracer enrichment of plasma cholesterol was not
      significantly different between the wheat germ with extracted-and-reconstituted
      phytosterol (0.305 +/- 0.022 micro mol tracer/mmol cholesterol) and the original
      wheat germ. CONCLUSION: The efficiency of cholesterol absorption from test meals
      was substantially lower after consumption of original wheat germ than after
      consumption of phytosterol-free wheat germ, which suggests that endogenous
      phytosterols in wheat germ and possibly in other low-fat vegetable foods may have
      important effects on cholesterol absorption and metabolism that are independent
      of major nutrients.

PMID- 12791615
TI  - Dietary carotenoids and risk of coronary artery disease in women.
AB  - BACKGROUND: Numerous studies have shown that higher intakes or higher blood
      concentrations of carotenes are associated with a lower risk of coronary artery
      disease (CAD). Given the null results in trials of beta-carotene supplementation,
      considerable attention has focused on the potential role of other dietary
      carotenoids in the prevention of CAD. OBJECTIVE: Our objective was to
      prospectively examine the relation between dietary intakes of specific
      carotenoids and risk of CAD in women. DESIGN: In 1984, 73 286 female nurses
      completed a semiquantitative food-frequency questionnaire that assessed their
      consumption of carotenoids and various other nutrients. The women were followed
      for 12 y for the development of incident CAD (nonfatal myocardial infarction and
      fatal CAD), and dietary information was updated in 1986, 1990, and 1994. RESULTS:
      During 12 y of follow-up (803 590 person-years), we identified 998 incident cases
      of CAD. After adjustment for age, smoking, and other CAD risk factors, we
      observed modest but significant inverse associations between the highest
      quintiles of intake of beta-carotene and alpha-carotene and risk of CAD but no
      significant relation with intakes of lutein/zeaxanthin, lycopene, or beta
      cryptoxanthin. For women in the highest compared with the respective lowest
      quintile of intake, the relative risks for beta-carotene and alpha-carotene were
      0.74 (95% CI: 0.59, 0.93) and 0.80 (95% CI: 0.65, 0.99), respectively. The
      association between the specific carotenoids and CAD risk did not vary
      significantly by current smoking status. CONCLUSION: Higher intakes of foods rich
      in alpha-carotene or beta-carotene are associated with a reduction in risk of
      CAD.

PMID- 12791616
TI  - Flavonoid intake and the risk of cardiovascular disease in women.
AB  - BACKGROUND: Despite emerging evidence of the role of flavonoids in cardiovascular
      disease (CVD) prevention, the association remains unclear. OBJECTIVE: We examined
      whether flavonoids and selected flavonols and flavones or their food sources are
      associated with CVD risk. DESIGN: Women (n = 38 445) free of CVD and cancer
      participated in a prospective study with a mean follow-up of 6.9 y. On the basis
      of a food-frequency questionnaire, total flavonoids and selected flavonols and
      flavones were categorized into quintiles, and food sources were categorized into
      4 groups. Relative risks were computed for important vascular events (519 events;
      excluding revascularizations) and CVD (729 events), including myocardial
      infarction, stroke, revascularization, and CVD death. RESULTS: The mean flavonoid
      intake was 24.6 +/- 18.5 mg/d, primarily as quercetin (70.2%). For both CVD and
      important vascular events, no significant linear trend was observed across
      quintiles of flavonoid intake (P = 0.63 and 0.80, respectively). No individual
      flavonol or flavone was associated with CVD. Broccoli and apple consumption were
      associated with nonsignificant reductions in CVD risk: 25-30% and 13-22%,
      respectively. A small proportion of women (n = 1185) consuming > or =4 cups (946
      mL) tea/d had a reduction in the risk of important vascular events but with a
      nonsignificant linear trend (P = 0.07). CONCLUSIONS: Flavonoid intake was not
      strongly associated with a reduced risk of CVD. The nonsignificant inverse
      associations for broccoli, apples, and tea with CVD were not mediated by
      flavonoids and warrant further study.

PMID- 12791617
TI  - Relative influence of diet and physical activity on body composition in urban
      Chinese adults.
AB  - BACKGROUND: The relative influence of diet and physical activity on body fatness
      remains uncertain. OBJECTIVE: The objective of the study was to investigate
      associations of dietary variables and physical activity with body fatness in
      urban Chinese adults. DESIGN: We conducted a cross-sectional study in 130 weight
      stable men and women aged 35-49 y. Subjects were selected from upper and lower
      tertiles of dietary fat and physical activity on the basis of screening
      questionnaires. Dietary intake was assessed by weighed food intake, physical
      activity level (PAL) was calculated as the ratio of predicted total energy
      expenditure (TEE) to predicted resting energy expenditure, and body composition
      was measured with the use of (2)H(2)O. Reported energy intake and predicted TEE
      were validated against TEE determined with the use of (2)H(2)(18)O (n = 73).
      RESULTS: Body fatness was positively associated with dietary variety (ie, variety
      of ingredients) (partial r = 0.186, P = 0.039) and frequency of consuming
      restaurant foods (partial r = 0.237, P = 0.001) and negatively associated with
      PAL (partial r = -0.307, P = 0.001) in a multiple regression analysis that
      controlled for sex and confounders. The combined variance accounted for by
      dietary variety and restaurant food consumption (9.1%) was equivalent to that for
      PAL (9.4%). Neither dietary fat nor energy density predicted body fatness, but
      dietary energy density predicted within-subject day-to-day variation in reported
      energy intake (P < 0.001). CONCLUSIONS: Dietary variety, frequency of restaurant
      food consumption, and PAL significantly predicted body fatness in urban Chinese
      adults, but dietary fat did not. These findings support previous studies in US
      adults and suggest that dietary variables other than fat have an important
      influence on adult body composition.

PMID- 12791618
TI  - Dietary patterns and changes in body mass index and waist circumference in
      adults.
AB  - BACKGROUND: Obesity has increased > 20% in the past decade in the United States,
      and more than one-half of US adults are overweight or obese. OBJECTIVE: Our
      objective was to further elucidate the nutritional etiology of changes in body
      mass index (BMI; in kg/m(2)) and waist circumference by dietary intake pattern.
      We hypothesized that a healthy dietary pattern would lead to smaller changes in
      BMI and waist circumference than would other dietary patterns. DESIGN: Subjects
      were 459 healthy men and women participating in the ongoing Baltimore
      Longitudinal Study of Aging. Diet was assessed with the use of 7-d dietary
      records, from which 41 food groups were created and entered into a cluster
      analysis. RESULTS: Five dietary patterns were derived (healthy, white bread,
      alcohol, sweets, and meat and potatoes). The mean annual change in BMI was 0.30
      +/- 0.06 for subjects in the meat-and-potatoes cluster and 0.05 +/- 0.06 for
      those in the healthy cluster (P < 0.01). The mean annual change in waist
      circumference was more than 3 times as great for subjects in the white-bread
      cluster (1.32 +/- 0.29 cm) as for those in the healthy cluster (0.43 +/- 0.27 cm)
      (P < 0.05). CONCLUSIONS: Consuming a diet high in fruit, vegetables, reduced-fat
      dairy, and whole grains and low in red and processed meat, fast food, and soda
      was associated with smaller gains in BMI and waist circumference. Because foods
      are not consumed in isolation, dietary pattern research based on natural eating
      behavior may be useful in understanding dietary causes of obesity and in helping
      individuals trying to control their weight.

PMID- 12791619
TI  - Carbohydrate intake and biomarkers of glycemic control among US adults: the third
      National Health and Nutrition Examination Survey (NHANES III).
AB  - BACKGROUND: Recommendations for preventing and treating type 2 diabetes include
      consuming carbohydrates, predominantly from whole grains, fruit, vegetables, and
      low-fat milk. However, the quantity and type of carbohydrates consumed may
      contribute to disorders of glycemic control. OBJECTIVE: We evaluated the
      association between carbohydrate intakes and biomarkers of glycemic control in a
      nationally representative sample of healthy US adults who participated in a cross
      sectional study, the third National Health and Nutrition Examination Survey.
      DESIGN: The sample (5730 men and 6125 women aged > or = 20 y) was divided into
      quintiles of carbohydrate intake (as a percentage of energy). Carbohydrate
      intakes were examined in relation to glycated hemoglobin (Hb A(1c)), plasma
      glucose, serum C-peptide, and serum insulin concentrations by using logistic
      regression. RESULTS: Carbohydrate intakes were not associated with Hb A(1c),
      plasma glucose, or serum insulin concentrations in men or women after adjustment
      for confounding variables. Carbohydrate intakes were inversely associated with
      serum C-peptide concentrations in men and women. Odds ratios for elevated serum C
      peptide concentrations for increasing quintiles of carbohydrate intake were 1.00,
      0.88, 0.57, 0.39, and 0.75 (P for trend = 0.016) in men, and 1.00, 0.69, 0.57,
      0.36, and 0.41 (P for trend = 0.007) in women. When carbohydrate intakes were
      further adjusted for intakes of total and added sugar, the association of serum C
      peptide with carbohydrate intakes was strengthened in men. CONCLUSIONS:
      Carbohydrate intakes were not associated with Hb A(1c), plasma glucose, or serum
      insulin concentrations but were inversely associated with the risk of elevated
      serum C-peptide; this supports current recommendations regarding carbohydrate
      intake in healthy adults.

PMID- 12791620
TI  - Dietary intakes and plasma concentrations of carotenoids and tocopherols in
      relation to glucose metabolism in subjects at high risk of type 2 diabetes: the
      Botnia Dietary Study.
AB  - BACKGROUND: The role of antioxidants in the pathogenesis of type 2 diabetes is
      uncertain. OBJECTIVE: We evaluated cross-sectional relations of dietary intakes
      and plasma concentrations of antioxidants with glucose metabolism in a high-risk
      population. DESIGN: The subjects were 81 male and 101 female first- and second
      degree, nondiabetic relatives of patients with type 2 diabetes. Antioxidant
      intake data were based on 3-d food records. Subjects taking supplements
      containing beta-carotene or alpha-tocopherol were excluded. Plasma antioxidant
      concentrations were measured by HPLC. By using multiple linear regression
      analysis and adjusting for demographic, anthropometric, and lifestyle covariates,
      we studied whether dietary and plasma alpha- and beta-carotene, lycopene, and
      alpha- and gamma-tocopherol were related to fasting and 2-h concentrations of
      glucose and nonesterified fatty acids during an oral-glucose-tolerance test, to
      the homeostasis model assessment index of insulin resistance, and to measures of
      beta cell function (incremental 30-min serum insulin concentration during an oral
      glucose-tolerance test and first-phase insulin secretion during an intravenous
      glucose-tolerance test). RESULTS: In men, dietary carotenoids were inversely
      associated with fasting plasma glucose concentrations (P < 0.05), plasma beta
      carotene concentrations were inversely associated with insulin resistance (P =
      0.003), and dietary lycopene was directly related to baseline serum
      concentrations of nonesterified fatty acids (P = 0.034). In women, dietary alpha
      tocopherol and plasma beta-carotene concentrations were inversely and directly
      associated, respectively, with fasting plasma glucose concentrations (P < 0.05).
      In both sexes, cholesterol-adjusted alpha-tocopherol concentrations were directly
      associated with 2-h plasma glucose concentrations (P < 0.05). CONCLUSION: The
      data suggest an advantageous association of carotenoids, which are markers of
      fruit and vegetable intake, with glucose metabolism in men at high risk of type 2
      diabetes.

PMID- 12791621
TI  - Effect of chewing gum containing nicotine and caffeine on energy expenditure and
      substrate utilization in men.
AB  - BACKGROUND: Nicotine replacement therapy limits weight gain after smoking
      cessation. This finding is partly attributable to the thermogenic effect of
      nicotine, which may be enhanced by caffeine. OBJECTIVE: We assessed the acute
      thermogenic effects of chewing gum containing different doses of nicotine and
      caffeine. DESIGN: This randomized, double-blind, placebo-controlled, crossover
      study included 12 healthy, normal-weight men (aged 18-45 y). Energy expenditure
      was measured with indirect calorimetry before and 2.5 h after subjects chewed
      each of 7 different types of gum containing the following doses of
      nicotine/caffeine: 0/0, 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg/mg. RESULTS:
      The thermogenic responses (increases over the response to placebo) were 3.7%,
      4.9%, 7.9%, 6.3%, 8.5%, and 9.8%, respectively, for the gums containing 1/0, 2/0,
      1/50, 2/50, 1/100, and 2/100 mg nicotine/mg caffeine (P < 0.05 for all). Adding
      caffeine to 1 and 2 mg nicotine significantly enhanced the thermogenic response,
      but changing the caffeine dose (from 50 to 100 mg) did not change the thermogenic
      effect. None of the combinations changed the respiratory quotient compared with
      placebo, which indicates that glucose and fat oxidation rates were increased to a
      similar extent. Side effects occurred only with 2 mg nicotine. CONCLUSIONS: One
      milligram of nicotine has a pronounced thermogenic effect, which can be increased
      by approximately 100% by adding 100 mg caffeine. Increasing the nicotine dose to
      2 mg does not increase the thermogenic effect but produces side effects in most
      subjects. Caffeine may be useful in preventing weight gain after smoking
      cessation if its thermogenic effect can be used to enhance nicotine's effect on
      long-term energy balance.

PMID- 12791622
TI  - Calcium intake, body composition, and lipoprotein-lipid concentrations in adults.
AB  - BACKGROUND: Recent data suggest that variations in calcium intake may influence
      lipid metabolism and body composition. OBJECTIVE: The association between daily
      calcium intake and body composition and plasma lipoprotein-lipid concentrations
      was studied cross-sectionally in adults from phase 2 of the Quebec Family Study.
      DESIGN: Adults aged 20-65 y (235 men, 235 women) were studied. Subjects who
      consumed vitamin or mineral supplements were excluded. Subjects were divided into
      3 groups on the basis of their daily calcium intake: groups A (< 600 mg), B (600
      1000 mg), and C (> 1000 mg). RESULTS: Daily calcium intake was negatively
      correlated with plasma LDL cholesterol, total cholesterol, and total:HDL
      cholesterol in women and men after adjustment for variations in body fat mass and
      waist circumference (P < 0.05). In women, a significantly greater ratio of total
      to HDL cholesterol (P < 0.05) was observed in group A than in group C after
      correction for body fat mass and waist circumference. In women, body weight,
      percentage body fat, fat mass, body mass index, waist circumference, and total
      abdominal adipose tissue area measured by computed tomography were significantly
      greater (P < 0.05) in group A than in groups B and C, even after adjustments for
      confounding variables. Comparable trends were observed in men, but not after
      adjustment for the same covariates. CONCLUSION: A low daily calcium intake is
      associated with greater adiposity, particularly in women. In both sexes, a high
      calcium intake is associated with a plasma lipoprotein-lipid profile predictive
      of a lower risk of coronary heart disease risk compared with a low calcium
      intake.

PMID- 12791623
TI  - Development of a dried whole-blood spot thyroglobulin assay and its evaluation as
      an indicator of thyroid status in goitrous children receiving iodized salt.
AB  - BACKGROUND: Serum thyroglobulin appears to be a sensitive marker of thyroid
      dysfunction in endemic goiter. However, its value as an indicator of thyroid
      status in children after the introduction of iodized salt has not been tested.
      OBJECTIVE: The objective was to optimize and validate a thyroglobulin assay on
      dried whole blood spots and to evaluate thyroglobulin as an indicator of thyroid
      response to iodized salt. DESIGN: A standardized, commercially available,
      sandwich fluoroimmunometric serum thyroglobulin assay was adapted for use on
      blood spots and validated in Swiss children. In a 1-y prospective study in 377
      goitrous Moroccan children aged 6-15 y, the assay was used to measure
      thyroglobulin before and after the introduction of iodized salt. Urinary iodine,
      thyroid volume, thyrotropin, and thyroxine were measured, and regression was done
      with thyroglobulin as the dependent variable. RESULTS: Correlation between the
      blood spot and serum assays was excellent (r = 0.98). The SD of the difference
      between the blood spot and serum assays was 3.8 micro g/L; the median CVs for the
      blood spot assay in controls and samples were 6.3% and 14.4%, respectively.
      Median thyroglobulin was 24.5 (range: 0-328.8) micro g/L at baseline and fell
      significantly after the introduction of iodized salt to 6.2 (0-83.1) and 4.4 (0
      47.1) micro g/L at 5 and 12 mo, respectively (P < 0.0001). Regression of urinary
      iodine and thyroid volume on thyroglobulin was highly significant at baseline and
      at 5 mo (P < 0.001). CONCLUSION: Thyroglobulin, measured in dried whole blood
      spots, may be a valuable indicator of improving thyroid function in children
      after supplementation with iodized salt.

PMID- 12791624
TI  - Bioavailability of soybean isoflavones from aglycone and glucoside forms in
      American women.
AB  - BACKGROUND: Test results on the bioavailability of isoflavones in the aglycone or
      glucoside form in Eastern and Western human subjects are contradictory.
      OBJECTIVE: The objective was to investigate the bioavailability of the soy
      isoflavones daidzein and genistein in American women with typical American
      dietary habits after ingestion of the aglycone or glucoside form of isoflavones.
      DESIGN: Fifteen American women aged 46 +/- 6 y participated in a randomized,
      double-blind study. Blood samples were collected 0, 1, 2, 4, 8, 12, 24, and 48 h
      after consumption of aglycone or glucoside tablets with breakfast. The plasma
      curves for daidzein, genistein, and equol were constructed and the postprandial
      maximum concentration (C(max)), time to the maximum concentration (t(max)), and
      area under the curve (AUC) were determined. RESULTS: Isoflavone concentrations
      peaked early (1-2 h) in plasma and peaked again at 4-8 h. Mean C(max), t(max),
      and AUC values for genistein were not significantly different after ingestion of
      aglycone or glucoside. However, C(max) and AUC values, but not t(max), were
      significantly higher for daidzein after aglycone ingestion, which was partly due
      to its higher content in the aglycone tablets. Equol appeared after 4 h and
      remained elevated after 48 h. Despite a higher content of daidzein in the
      aglycone tablets, the AUC for equol was significantly higher after ingestion of
      the glucoside tablets, probably because of the metabolic action of intestinal
      bacteria during the long intestinal transit time of glucoside. CONCLUSION: The
      apparent bioavailability of genistein and daidzein is not different when consumed
      as either aglycone or glucoside by American women.

PMID- 12791625
TI  - Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit
      platelet function.
AB  - BACKGROUND: Flavonoids may be partly responsible for some health benefits,
      including antiinflammatory action and a decreased tendency for the blood to clot.
      An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits
      platelet activation and function over 6 h in humans. OBJECTIVE: This study sought
      to evaluate whether 28 d of supplementation with cocoa flavanols and related
      procyanidin oligomers would modulate human platelet reactivity and primary
      hemostasis and reduce oxidative markers in vivo. DESIGN: Thirty-two healthy
      subjects were assigned to consume active (234 mg cocoa flavanols and
      procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d)
      tablets in a blinded parallel-designed study. Platelet function was determined by
      measuring platelet aggregation, ATP release, and expression of activation
      dependent platelet antigens by using flow cytometry. Plasma was analyzed for
      oxidation markers and antioxidant status. RESULTS: Plasma concentrations of
      epicatechin and catechin in the active group increased by 81% and 28%,
      respectively, during the intervention period. The active group had significantly
      lower P selectin expression and significantly lower ADP-induced aggregation and
      collagen-induced aggregation than did the placebo group. Plasma ascorbic acid
      concentrations were significantly higher in the active than in the placebo group
      (P < 0.05), whereas plasma oxidation markers and antioxidant status did not
      change in either group. CONCLUSIONS: Cocoa flavanol and procyanidin
      supplementation for 28 d significantly increased plasma epicatechin and catechin
      concentrations and significantly decreased platelet function. These data support
      the results of acute studies that used higher doses of cocoa flavanols and
      procyanidins.

PMID- 12791626
TI  - Low vitamin B-12 concentrations in patients without anemia: the effect of folic
      acid fortification of grain.
AB  - BACKGROUND: In some patients with vitamin B-12 deficiency mistakenly treated with
      folic acid, anemia resolved but neurologic complications became worse (masking).
      Fortification of enriched cereal grains with folic acid has raised concerns that
      people who consume large quantities of cereal grains, particularly the elderly,
      may be at increased risk of masking. It is unclear, however, what proportion of
      people with low vitamin B-12 concentrations do not have anemia and whether the
      proportion is increasing. OBJECTIVE: We investigated whether fortification has
      increased the proportion of patients with low vitamin B-12 but without anemia.
      DESIGN: We reviewed the laboratory results of every patient for whom a vitamin B
      12 concentration was measured at the Veterans Affairs Medical Center in
      Washington, DC, between 1992 and 2000. Those with a low vitamin B-12
      concentration (< 258 pmol/L) had their hematocrits and mean cell volumes checked.
      The proportion without anemia was examined by year before, during, and after
      folic acid fortification began. RESULTS: There were 1573 subjects with a low
      vitamin B-12 concentration. The proportion without anemia did not increase
      significantly from the prefortification period (39.2%) to the period of optional
      fortification (45.5%) and the postfortification period (37.6%). These findings
      did not change when the analysis was limited to patients aged > 60 y or when a
      more conservative definition of low vitamin B-12 (< 150 pmol/L) was used.
      CONCLUSIONS: Despite evidence that folic acid exposure has increased dramatically
      since food fortification began, this population showed no evidence of an increase
      in low vitamin B-12 concentrations without anemia. If confirmed, these results
      would indicate that food fortification has not caused a major increase in masking
      of vitamin B-12 deficiency.

PMID- 12791627
TI  - Fortification of orange juice with vitamin D: a novel approach for enhancing
      vitamin D nutritional health.
AB  - BACKGROUND: Fortification of milk with vitamin D may not be adequate for
      satisfying the vitamin D requirement because of variability in vitamin D content
      after fortification and because many persons have milk allergy or lactose
      intolerance. Additional foods need to be fortified with vitamin D. OBJECTIVE: We
      determined whether vitamin D, a fat-soluble vitamin, is bioavailable in orange
      juice and skim milk, 2 nonfat beverages. DESIGN: On 3 separate occasions, 18
      adults ingested 25 000 IU vitamin D(2) in 240 mL whole milk or skim milk or in
      0.1 mL corn oil applied to toast. A separate, double-blind, randomized,
      controlled trial investigated whether the consumption of orange juice fortified
      with vitamin D(3) would increase serum 25-hydroxyvitamin D [25(OH)D]
      concentrations: 14 subjects ingested 240 mL orange juice fortified with 1000 IU
      vitamin D, and 12 subjects ingested a control orange juice daily for 12 wk.
      RESULTS: Peak serum vitamin D(2) concentrations did not differ significantly
      after the ingestion of vitamin D(2) in whole milk, skim milk, or corn oil on
      toast. After subjects consumed orange juice fortified with 1000 IU vitamin D(3)
      daily for 12 wk, serum 25(OH)D(3) concentrations increased by 150%, and serum
      parathyroid hormone concentrations decreased by 25% compared with baseline;
      control subjects had a seasonal increase of 45% in 25(OH)D and no significant
      change in serum parathyroid hormone. CONCLUSIONS: The fat content of milk does
      not affect vitamin D bioavailability. Vitamin D fortification at 1000 IU/240 mL
      orange juice for 12 wk safely increased 25(OH)D(3) concentrations in adults.

PMID- 12791628
TI  - Combined deficiency of vitamins E and C causes paralysis and death in guinea
      pigs.
AB  - BACKGROUND: On the basis of in vitro studies, the antioxidant nutrients vitamins
      E and C are postulated to interact in vivo. OBJECTIVE: We developed a guinea pig
      model to evaluate the combined deficiency of vitamins E and C in vivo. DESIGN:
      Weanling guinea pigs were fed a control diet or a vitamin E-deficient diet for 14
      d, after which one-half of each group had vitamin C removed from their diet, thus
      creating 4 diet groups. Some animals were observed for clinical signs. Others
      were killed for evaluation. RESULTS: Of 21 guinea pigs that were observed after
      being fed the diet deficient in both vitamins, 8 died 9 +/- 2 d (x +/- SD) after
      starting the diet. Eight additional guinea pigs developed a characteristic
      syndrome at 11 +/- 3 d. First, they became paralyzed in the hind limbs. Within a
      few hours, the paralysis progressed to include all 4 limbs and caused difficulty
      in breathing, which would have caused death had the animals not been euthanized.
      Histopathologic evaluation did not identify a lesion in the muscles or nervous
      system that could account for the paralysis. Biochemical measurements confirmed
      the deficiencies and indicated that the double deficiency caused lipid
      peroxidation in the central nervous system. CONCLUSIONS: A distinct clinical
      syndrome of combined vitamin E and vitamin C deficiency occurs in guinea pigs.
      This syndrome indicates that these antioxidant vitamins are related in vivo. We
      speculate that acute oxidative injury in the central nervous system underlies the
      clinical syndrome.

PMID- 12791629
TI  - Infant nutrition and blood pressure in early adulthood: the Barry Caerphilly
      Growth study.
AB  - BACKGROUND: Evidence suggests that environmental factors acting early in life may
      affect blood pressure in adulthood. OBJECTIVE: The objective was to test the
      hypothesis that dried formula milk (derived from cow milk) intake in infancy is
      positively associated with blood pressure in early adulthood. DESIGN: We
      conducted a long-term follow-up (1997-1999) of the Barry Caerphilly Growth study
      cohort (1972-1974) into which mothers and their offspring had originally been
      randomly assigned to receive a milk supplement or usual care. Participants were
      the offspring, who were aged 23-27 y at follow-up. The main outcome measures were
      systolic and diastolic blood pressure. RESULTS: The social and demographic
      characteristics of the subjects who were (n = 679) and were not (n = 272)
      followed up were similar. For each increase in quartile of dried milk consumption
      (in oz) at 3 mo of age, there was a 1.28-mm Hg (95% CI: 0.46, 2.10 mm Hg)
      increase in systolic and a 0.63-mm Hg (95% CI: 0.04, 1.22 mm Hg) increase in
      diastolic blood pressure after adjustment for sex, intervention group, birth
      weight z scores, social class in childhood, age at follow-up, alcohol
      consumption, and pack-years of smoking. These coefficients were attenuated when
      adult body mass index and height were included in the models, but the association
      of dried milk consumption at 3 mo of age with systolic pressure remained
      significant (1.07 mm Hg; 95% CI: 0.27, 1.87 mm Hg). CONCLUSIONS: Our findings are
      consistent with the hypothesis that high blood pressure in later life is
      influenced by early postnatal nutrition. Thus, interventions to optimize infant
      nutrition may have important long-term health benefits.

PMID- 12791630
TI  - Associations between prenatal and postnatal growth and adult body size and
      composition.
AB  - BACKGROUND: Adult body size and composition (ABSC) measures are associated with
      work capacity and productivity, reproductive performance, and chronic disease
      risk. Growth failure in early childhood may have important long-term consequences
      through its influence on ABSC. OBJECTIVE: We assessed associations between
      prenatal and postnatal growth (0-2 y of age) and ABSC. DESIGN: We included 267
      singletons from a prospective study carried out between 1969 and 1977 in 4 ladino
      Guatemalan villages. We used data from that study and from a follow-up study
      conducted in 1998-1999 (when the subjects were 21-27 y of age) to determine
      associations of birth weight, length at 15 d of age, ponderal index, and length
      at 2 y of age with adult height, weight, fat-free mass (FFM), fat mass,
      percentage of body fat, and waist-to-hip ratio. Multivariate linear regression
      analyses with mixed models were carried out to account for sibling clustering.
      Two-stage least-squares analyses were used to separate specific effects of
      prenatal and postnatal growth. RESULTS: Birth weight, length at 15 d of age, and
      length at 2 y of age were positively associated with height, weight, and FFM in
      both sexes (P < 0.05). Prenatal growth and postnatal growth were equally
      important determinants of height, weight, and FFM. Weak positive associations of
      postnatal growth with adult fat mass and percentage of body fat were found in
      both sexes, whereas similar associations for prenatal growth were found in women
      only. Growth in early childhood was not related to waist-to-hip ratio.
      CONCLUSIONS: Growth retardation in early childhood was associated with shortness
      and less FFM in adulthood. Preventing growth failure in utero and preventing
      growth failure during the first 2 y of life are equally important for ABSC.

PMID- 12791631
TI  - Larger mass of high-metabolic-rate organs does not explain higher resting energy
      expenditure in children.
AB  - BACKGROUND: Children have a high resting energy expenditure (REE) relative to
      their body weight. The decline in REE during growth may be due to changes in body
      composition or to changes in the metabolic rate of individual organs and tissues.
      OBJECTIVES: The goals were to quantify body-composition components in children at
      the organ-tissue level in vivo and to determine whether the observed masses 1)
      account for the elevated REE in children and 2) account, when combined with
      specific organ-tissue metabolic constants, for children's REE. DESIGN: This was a
      cross-sectional evaluation of 15 children (aged 9.3 +/- 1.7 y) and 13 young
      adults (aged 26.0 +/- 1.8 y) with body mass indexes (in kg/m(2)) < 30. Magnetic
      resonance imaging-derived in vivo measures of brain, liver, kidney, heart,
      skeletal muscle, and adipose tissue were acquired. REE was measured by indirect
      calorimetry (REE(m)). Previously published organ-tissue metabolic rate constants
      were used to calculate whole-body REE (REE(c)). RESULTS: The proportion of
      adipose-tissue-free mass as liver (3.7 +/- 0.5% compared with 3.1 +/- 0.5%; P <
      0.01) and brain (6.2 +/- 1.2% compared with 3.3 +/- 0.9%; P < 0.001) was
      significantly greater in children than in young adults. The addition of brain and
      liver mass significantly improved the model but did not eliminate the role of
      age. REE(c) with published metabolic coefficients underestimated REE(m) (REE(c) =
      3869 +/- 615 kJ/d; REE(m) = 5119 +/- 769 kJ/d; P < 0.001) in children.
      CONCLUSION: The decline in REE during growth is likely due to both a decrease in
      the proportion of some of the more metabolically active organs and tissues and
      changes in the metabolic rate of individual organs and tissues.

PMID- 12791632
TI  - Effect of zinc supplementation of pregnant women on the mental and psychomotor
      development of their children at 5 y of age.
AB  - BACKGROUND: A negative effect of prenatal zinc deficiency on brain function has
      been well established in experimental animals, but this association in humans is
      controversial. OBJECTIVE: We evaluated the effect of prenatal zinc
      supplementation on the mental and psychomotor development of 355 children whose
      mothers participated in a double-blind trial of zinc supplementation that
      resulted in increased head circumference and birth weight. DESIGN: The children
      took 6 tests-the Differential Ability Scales, Visual Sequential Memory, Auditory
      Sequential Memory, Knox Cube, Gross Motor Scale, and Grooved Pegboard tests-at a
      mean age of 5.3 y. The scores were compared between the children of women who
      received a daily oral dose of 25 mg Zn during the second half of pregnancy and
      the children of women who received placebo. RESULTS: There were no differences in
      the test scores of neurologic development between the 2 groups. We analyzed the
      scores in 4 subgroups on the basis of maternal body mass index, because the
      increases in birth weight and head circumference due to the supplementation
      occurred only in the children of women with a body mass index (in kg/m(2)) < 26.0
      in the original trial. No differences in the scores were found between these
      subgroups. CONCLUSIONS: Zinc supplementation of women in the latter half of
      pregnancy had no effect on the neurologic development of their children at age 5
      y. It is not known whether our findings of no positive effect in the population
      with apparently inadequate zinc nutriture can be readily extrapolated to other
      populations.

PMID- 12791633
TI  - Protein intake: effects on bone mineral density and the rate of bone loss in
      elderly women.
AB  - BACKGROUND: The role of dietary protein in bone metabolism is controversial.
      OBJECTIVE: We investigated the associations of dietary protein intake with
      baseline bone mineral density (BMD) and the rate of bone loss over 3 y in
      postmenopausal elderly women. DESIGN: Women aged 65-77 y (n = 489) were enrolled
      in an osteoporosis intervention trial. We studied the associations of protein
      intake as a percentage of energy with baseline BMD and the rate of bone loss in
      96 women in the placebo group (n = 96). We also examined the effect of the
      interaction of dietary calcium intake with protein intake on BMD. RESULTS: In the
      cross-sectional study, a higher intake of protein was associated with higher BMD.
      BMD was significantly higher (P < 0.05) in the spine (7%), midradius (6%), and
      total body (5%) in subjects in the highest quartile of protein intake than in
      those in the lower 2 quartiles. This positive association was seen in women with
      calcium intakes > 408 mg/d. There was no significant effect of protein intake on
      hip BMD. In the longitudinal study of the placebo group, there was no association
      between protein intake and the rate of bone loss. CONCLUSIONS: The highest
      quartile of protein intake (: 72 g/d) was associated with higher BMD in elderly
      women at baseline only when the calcium intake exceeded 408 mg/d. In the
      longitudinal study, no association was seen between protein intake and the rate
      of bone loss, perhaps because the sample size was too small or the follow-up
      period of 3 y was not long enough to detect changes.

PMID- 12791634
TI  - Physical activity and fatness in prepubertal children.

PMID- 12791636
TI  - Uncoupling protein genes and racial differences in obesity.

PMID- 12791637
TI  - High birth weight does not guarantee protection from type 2 diabetes.

PMID- 12791645
TI  - Gene profiling of a myeloma cell line reveals similarities and unique signatures
      among IL-6 response, N-ras-activating mutations, and coculture with bone marrow
      stromal cells.
AB  - ANBL-6, a myeloma cell line, proliferates in response to interleukin 6 (IL-6)
      stimulation, coculture with bone marrow stromal cells, and when harboring a
      constitutively active mutant N-ras gene. Eighteen samples, including 4 IL-6
      treated, 3 mutant N-ras-transfected, 3 normal stroma-stimulated, 2 multiple
      myeloma (MM) stroma-stimulated, and 6 untreated controls were profiled using
      microarrays interrogating 12 626 genes. Global hierarchical clustering analysis
      distinguished at least 6 unique expression signatures. Notably, the different
      stimuli altered distinct functional gene programs. Class comparison analysis (P
      =.001) revealed 138 genes (54% involved in cell cycle) that distinguished IL-6
      stimulated versus nontreated samples. Eighty-seven genes distinguished stroma
      stimulated versus IL-6-treated samples (22% encoded for extracellular matrix
      [ECM] proteins). A total of 130 genes distinguished N-ras transfectants versus IL
      6-treated samples (26% involved in metabolism). A total of 157 genes, 20% of
      these involved in signaling, distinguished N-ras from stroma-interacting samples.
      All 3 stimuli shared 347 genes, mostly of metabolic function. Genes that
      distinguished MM1 from MM4 clinical groups were induced at least by one
      treatment. Notably, only 3 genes (ETV5, DUSP6, and KIAA0735) are uniquely induced
      in mutant ras-containing cells. We have demonstrated gene expression patterns in
      myeloma cells that distinguish an intrinsic genetic transformation event and
      patterns derived from both soluble factors and cell contacts in the bone marrow
      microenvironment.

PMID- 12791647
TI  - Phase 2 clinical and pharmacologic study of clofarabine in patients with
      refractory or relapsed acute leukemia.
AB  - In a phase 2 study, 62 patients with relapsed and refractory acute myeloid
      leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid
      leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n
      = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days,
      every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had
      a partial response (PR), and 9 (15%) achieved CR but without platelet recovery
      (CRp), for an overall response rate of 48%. In AML, responses were noted in 2
      (18%) of 11 patients in first salvage with short first CR (</= 12 months), in 7
      (87%) of 8 patients with longer first CR, and in 8 (67%) of 12 patients in second
      or subsequent salvage. Responses were observed in 4 of 8 patients with high-risk
      MDS (50%), in 7 (64%) of 11 with CML-BP, and in 2 (17%) of 12 with ALL. Severe
      reversible liver dysfunction was noted in 15% to 25%. After the first clofarabine
      infusion, responders accumulated more clofarabine triphosphate in blasts compared
      with nonresponders (median 18 vs 10 microM; P =.03). This increased only in
      responders (median, 1.8-fold; P =.008) after the second clofarabine infusion. In
      summary, clofarabine is active in acute leukemias and MDS; cellular
      pharmacokinetics may have prognostic significance.

PMID- 12791646
TI  - A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell
      differentiation and hematopoiesis.
AB  - Homozygous mutant (Shp-2Delta46-110) embryonic stem (ES) cells exhibit decreased
      hematopoiesis; however, the point at which Shp-2 is critical for ES cell
      differentiation to hematopoietic cells is unknown. We characterized the
      differentiation defect of Shp-2Delta46-110 ES cells by examining early points of
      differentiation, conducting leukemia inhibitory factor (LIF)-stimulated
      biochemical analysis, and performing in vitro reconstitution studies with wild
      type (WT) Shp-2. ES cell in vitro differentiation assays were used to compare the
      differentiation of WT, Shp-2Delta46-110, and reconstituted ES cells to mesoderm,
      by measuring brachyury expression, to hemangioblasts, by measuring blast colony
      forming cell (BL-CFC) formation and flk-1 expression, and to hematopoietic
      progenitor colony-forming cells, by performing secondary plating assays. LIF
      stimulated phospho-Stat3 (known to be critical for ES cell self-renewal and
      maintenance of an undifferentiated state) and phospho-Erk levels were examined by
      immunoblotting. ES cell survival, using annexin V staining, and secondary
      embryoid body (EB) formation were also evaluated. Differentiation to both
      mesoderm and hemangioblasts was lower in Shp-2Delta46-110 cells compared to WT
      cells. On reconstitution with WT Shp-2, expression of brachyury and flk-1 and
      differentiation to hemangioblasts and primitive and definitive hematopoietic
      progenitors were restored. LIF-stimulated phospho-Stat3 levels were higher,
      whereas phospho-Erk levels were lower in Shp-2Delta46-110 ES cells than in WT and
      reconstituted cells. The increased phospho-Stat3 levels correlated with increased
      Shp-2Delta46-110 ES cell secondary EB formation and survival. We conclude that
      normal Shp-2 function is critical for the initial step of ES cell differentiation
      to mesoderm and to hemangioblasts and acts within the LIF-gp130-Stat3 pathway to
      maintain a proper balance of ES cell differentiation, pluripotency, and
      apoptosis.

PMID- 12791648
TI  - A dendritic cell vaccine against invasive aspergillosis in allogeneic
      hematopoietic transplantation.
AB  - Dendritic cells (DCs) have a remarkable functional plasticity in response to
      conidia and hyphae of the fungus Aspergillus fumigatus. In the present study we
      sought to assess the capacity of DCs activated by live fungi or fungal RNA to
      generate antifungal immunity in vivo. We found that both human and murine DCs
      pulsed with live fungi or transfected with fungal RNA underwent functional
      maturation, as revealed by the up-regulated expression of histocompatibility
      class II antigen and costimulatory molecules and the production of interleukin 12
      (IL-12) in response to conidia or conidial RNA and of IL-4/IL-10 in response to
      hyphae or hyphal RNA. DCs pulsed with conidia or transfected with conidial RNA
      activated antigen-specific, interferon gamma (IFN-gamma)-producing T lymphocytes
      in vitro and in vivo on adoptive transfer in mice otherwise susceptible to
      aspergillosis. TH1-dependent antifungal resistance could also be induced in mice
      receiving allogeneic bone marrow transplants and was associated with an
      accelerated recovery of myeloid and lymphoid cells. Because the efficacy of the
      infusion of DCs was superior to that obtained on the adoptive transfer of
      Aspergillus-specific T cells, these results indicate the vaccinating potential of
      DCs pulsed with Aspergillus conidia or conidial RNA in hematopoietic
      transplantation.

PMID- 12791649
TI  - Sex-specific alterations in neutrophil apoptosis: the role of estradiol and
      progesterone.
AB  - Women are conferred with greater immunologic and survival benefits compared to
      men. Female sex steroids contribute to this sexual dimorphism. Furthermore,
      during human pregnancy when female sex hormones are elevated, neutrophil
      apoptosis is delayed. This study examines the specific effects of estradiol and
      progesterone on neutrophil apoptosis and function in healthy adult men and women.
      We also examined the contribution of these hormones to the persistence and
      resolution of an inflammatory response. Spontaneous apoptosis was significantly
      decreased in women compared with men. Physiologic doses of estradiol and
      progesterone caused a further delay in spontaneous apoptosis in both men and
      women but did not diminish Fas antibody-induced apoptosis. The delay in apoptosis
      was mediated at the level of the mitochondria with decreased release of
      cytochrome c, which may alter caspase cleavage and activity. There were no
      associated alterations in neutrophil CD11b, but production of reactive oxygen
      intermediates (ROIs) in women was increased. Thus, female sex hormones mediate
      delayed neutrophil apoptosis in both sexes and enhance female intracellular
      production of ROIs. Modulating hormonal responses may be an effective therapeutic
      tool in combating inflammatory diseases.

PMID- 12791650
TI  - The homeoprotein Hex is required for hemangioblast differentiation.
AB  - The first hematopoietic and endothelial progenitors are derived from a common
      embryonic precursor termed the hemangioblast. The genetic cascades that regulate
      the differentiation of the hemangioblast to hematopoietic and endothelial cells
      are largely unknown. In general, much of embryonic development is coordinately
      regulated by temporal and spatial expression of transcription factors, such as
      the Homeobox (Hox) gene family. We and others isolated a divergent homeobox gene
      termed Hex (or Prh) that is preferentially expressed in hematopoietic and
      endothelial cells. Using in vitro Hex-/- embryonic stem (ES) cell
      differentiation, in vivo yolk sac hematopoietic progenitor assays, and chimeric
      mouse analysis, we found that Hex is required for differentiation of the
      hemangioblast to definitive embryonic hematopoietic progenitors and to a lesser
      extent endothelial cells. Therefore, Hex is a novel regulator of hemangioblast
      differentiation to hematopoietic and endothelial cells.

PMID- 12791651
TI  - Analysis of intracellular storage and regulated secretion of 3 von Willebrand
      disease-causing variants of von Willebrand factor.
AB  - The rapid exocytosis of von Willebrand factor (VWF) in response to vascular
      injury can be attributed to the fact that VWF is stored in the Weibel-Palade
      bodies (WPBs) of endothelial cells. We describe a system for examining the
      ability of VWF to drive both the formation of a storage compartment and the
      function of that compartment with respect to regulated secretion. Transient
      transfection of HEK293 cells with wild-type human VWF cDNA leads to the formation
      of numerous elongated organelles that resemble WPBs. These "pseudo-WPBs" exhibit
      the internal structure, as well as the ability to recruit membrane proteins
      including P-selectin, of bona fide WPBs. Finally, VWF was efficiently secreted
      upon stimulation by phorbol ester. We used this system to examine 3 VWF mutations
      leading to von Willebrand disease that affect VWF multimerization and
      constitutive secretion. Surprisingly we find that all 3 mutants can, to some
      extent, make pseudo-WPBs that recruit appropriate membrane proteins and that are
      responsive to secretagogues. The most striking defects are a delay in formation
      and a reduction in the length and number of pseudo-WPBs in proportion to the
      clinical severity of the mutation. Studies of pseudo-WPB formation in this system
      thus yield insights into the structure-function relationships underpinning the
      ability of VWF to form functional WPBs.

PMID- 12791652
TI  - Most lymphoid organ dendritic cell types are phenotypically and functionally
      immature.
AB  - Dendritic cells (DCs) have been thought to follow a life history, typified by
      Langerhans cells (LCs), with 2 major developmental stages: an immature stage that
      captures antigens in the periphery and a mature stage that presents those
      antigens in the lymphoid organs. However, a systematic assessment of the maturity
      of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC
      types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The
      DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs
      from peripheral tissues were mature and therefore could not process and present
      newly encountered antigens. However, all the other DC types were phenotypically
      and functionally immature: they expressed low levels of surface major
      histocompatibility complex class II (MHC II) and CD86, accumulated MHC II in
      their endosomes, and could present newly encountered antigens. These immature DCs
      could be induced to mature by culture in vitro or by inoculation of inflammatory
      stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of
      immature DCs, most likely for the maintenance of peripheral tolerance, which can
      respond to infections reaching those organs and mature in situ.

PMID- 12791653
TI  - Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for
      liver gene therapy.
AB  - We report the generation and use of pseudotyped adeno-associated viral (AAV)
      vectors for the liver-specific expression of human blood coagulation factor IX
      (hFIX). Therefore, an AAV-2 genome encoding the hfIX gene was cross-packaged into
      capsids of AAV types 1 to 6 using efficient, large-scale technology for particle
      production and purification. In immunocompetent mice, the resultant vector
      particles expressed high hFIX levels ranging from 36% (AAV-4) to more than 2000%
      of normal (AAV-1, -2, and -6), which would exceed curative levels in patients
      with hemophilia. Expression was dose- and time-dependent, with AAV-6 directing
      the fastest and strongest onset of hFIX expression at all doses. Interestingly,
      systemic administration of 2 x 1012 vector particles of AAV-1, -4, or -6 resulted
      in hFIX levels similar to those achieved by portal vein delivery. For all other
      serotypes and particle doses, hepatic vector administration yielded up to 84-fold
      more hFIX protein than tail vein delivery, corroborated by similarly increased
      vector DNA copy numbers in the liver, and elicited a reduced immune response
      against the viral capsids. Finally, neutralization assays showed variable
      immunologic cross-reactions between most of the AAV serotypes. Our technology and
      findings should facilitate the development of AAV pseudotype-based gene therapies
      for hemophilia B and other liver-related diseases.

PMID- 12791654
TI  - HLA-matched unrelated donor hematopoietic cell transplantation after
      nonmyeloablative conditioning for patients with hematologic malignancies.
AB  - A hematopoietic cell transplantation (HCT) approach was developed for elderly or
      ill patients with hematologic malignancies that employed nonmyeloablative
      conditioning to avoid common regimen-related toxicities and relied on graft
      versus-tumor effects for control of malignancy. Eighty-nine patients, median age
      53 years, were given fludarabine (90 mg/m2) and 2 Gy total body irradiation.
      Marrow (n = 18) or granulocyte colony-stimulating factor (G-CSF)-stimulated
      peripheral blood mononuclear cells (G-PBMCs; n = 71) were transplanted from
      unrelated donors matched for human leukocyte antigen A (HLA-A), -B, -C antigens
      and -DRB1 and -DQB1 alleles. Postgrafting immunosuppression included
      mycophenolate mofetil and cyclosporine. Donor T-cell chimerism was higher for G
      PBMCs compared with marrow recipients. Durable engraftment was observed in 85% of
      G-PBMCs and 56% of marrow recipients. Cumulative probabilities of grade II, III,
      and IV acute graft-versus-host disease (GVHD) were 42%, 8%, and 2%, respectively.
      Nonrelapse mortality at day 100 and at 1 year was 11% and 16%, respectively. One
      year overall survivals and progression-free survivals were 52% and 38%,
      respectively. G-PBMC recipients had improved survival (57% vs 33%) and
      progression-free survival (44% vs 17%) compared with marrow recipients. HLA
      matched unrelated donor HCT after nonmyeloablative conditioning is feasible in
      patients ineligible for conventional HCT. G-PBMCs conferred higher donor T-cell
      chimerism, greater durable engraftment, and better progression-free and overall
      survivals compared with marrow.

PMID- 12791655
TI  - Polymorphic variation in GSTP1 modulates outcome following therapy for multiple
      myeloma.
AB  - Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved
      in the metabolism and detoxification of a range of chemotherapeutic agents. A
      single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower
      thermal stability and altered catalytic activity. We hypothesized that patients
      with the less stable variant have a decreased ability to detoxify
      chemotherapeutic substrates, including melphalan, and have an altered outcome
      following treatment for multiple myeloma. We have assessed the impact of GSTP1
      codon 105 polymorphisms in 222 patients entered into the Medical Research Council
      (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose
      therapy). In the standard-dose arm, patients with the variant allele (105Val) had
      an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were
      0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile
      homozygotes; P for trend =.04); this was supported by a trend to improved overall
      survival, greater likelihood of entering plateau and shorter time to reach
      plateau in patients with the 105Val allele. No difference in outcome by genotype
      was found for patients treated with high-dose therapy. However, the progression
      free survival advantage of the high-dose arm was seen only in patients homozygous
      for 105Ile (P =.008).

PMID- 12791656
TI  - NF-Y cooperates with USF1/2 to induce the hematopoietic expression of HOXB4.
AB  - The transcription factor homeobox B4 (HOXB4) is preferentially expressed in
      immature hematopoietic cells and implicated in the transition from primitive
      hematopoiesis to definitive hematopoiesis as well as in immature hematopoietic
      cell proliferation and differentiation. We previously identified Hox response
      element 1 (HxRE-1) and HxRE-2/E-box as 2 critical DNA-binding sites of the HOXB4
      promoter active in hematopoietic cells and demonstrated that upstream stimulating
      factor 1 and 2 (USF1/2) activate HOXB4 transcription through their binding to the
      E-box site. Here we report that the trimeric regulatory complex nuclear factor Y
      (NF-Y) is the factor that recognizes HxRE-1 and activates the HOXB4 promoter in
      hematopoietic cells. We further show that NF-Y interacts biochemically with
      USF1/2 on the HOXB4 promoter, and that the formation of this NF-Y/USF1/2 complex
      is required for the full activity of the HOXB4 promoter. Most important, NF-Ya
      subunit protein levels are found to be lower in c-Kit-Gr-1+ granulocytic bone
      marrow (BM) cells than in c-Kit+ immature BM cells, in parallel with a reduction
      of NF-Y occupancy on the HOXB4 promoter as shown by chromatin immunoprecipitation
      (ChIP) assay. These results suggest that NF-Y is a developmentally regulated
      inducer of the HOXB4 gene in hematopoietic cells.

PMID- 12791657
TI  - Memory B cells producing somatically mutated antiphospholipid antibodies are
      present in healthy individuals.
AB  - Antiphospholipid antibodies (aPLs) are associated with thrombosis and recurrent
      abortions during autoimmune pathologies, but they are also produced in healthy
      individuals and during infectious diseases. To analyze the possible links between
      physiologic and pathologic aPLs, it is of importance to characterize normal aPL
      production. We took advantage of the known tropism of Epstein-Barr virus (EBV)
      for B cells in general, and memory B cells in particular, during primary
      infectious mononucleosis (IMN) in 3 patients to get access to anticardiolipin
      (aCL)-producing B cells. Flow cytometry analysis of these cells showed that,
      depending on the patient, 10% to 60% of immunoglobulin M (IgM) aCL-producing B
      cells express the CD27 marker of memory B cells. Single cell sorting of aCL B
      cells, followed by single cell reverse transcription-polymerase chain reaction
      (RT-PCR) amplification of their immunoglobulin variable region genes, showed that
      some of these cells produce mutated forms of aCL antibodies, confirming their
      memory B-cell origin. Considering that, during primary IMN, EBV infects and
      expands already pre-existing memory B cells, we conclude that healthy individuals
      have a discrete pool of aCL memory cells able to produce mutated forms of
      antibodies. The implications of this new information are discussed in light of
      different hypotheses regarding the origin of aCL.

PMID- 12791658
TI  - FLT3 and MLL intragenic abnormalities in AML reflect a common category of
      genotoxic stress.
AB  - MLL rearrangements in acute myeloid leukemia (AML) include translocations and
      intragenic abnormalities such as internal duplication and breakage induced by
      topoisomerase II inhibitors. In adult AML, FLT3 internal tandem duplications
      (ITDs) are more common in cases with MLL intragenic abnormalities (33%) than
      those with MLL translocation (8%). Mutation/deletion involving FLT3 D835 are
      found in more than 20% of cases with MLL intragenic abnormalities compared with
      10% of AML with MLL translocation and 5% of adult AML with normal MLL status.
      Real-time quantification of FLT3 in 141 cases of AML showed that all cases with
      FLT3 D835 express high level transcripts, whereas FLT3-ITD AML can be divided
      into cases with high-level FLT3 expression, which belong essentially to the
      monocytic lineage, and those with relatively low-level expression, which
      predominantly demonstrate PML-RARA and DEK-CAN. FLT3 abnormalities in CBF
      leukemias with AML1-ETO or CBFbeta-MYH11 were virtually restricted to cases with
      variant CBFbeta-MYH11 fusion transcripts and/or atypical morphology. These data
      suggest that the FLT3 and MLL loci demonstrate similar susceptibility to agents
      that modify chromatin configuration, including topoisomerase II inhibitors and
      abnormalities involving PML and DEK, with consequent errors in DNA repair.
      Variant CBFbeta-MYH11 fusions and bcr3 PML-RARA may also be initiated by similar
      mechanisms.

PMID- 12791659
TI  - Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate
      CML development.
AB  - We have previously found that P210BCR-ABL increases the adhesion of hematopoietic
      cell lines to fibronectin by a mechanism that is independent of tyrosine kinase
      activity. To investigate the pathway(s) by which P210BCR-ABL influences cell
      adhesion, we used a quantitative cell adhesion device that can discern small
      changes in cell adhesion to assay P210BCR-ABL with mutations in several critical
      domains. We expressed P210BCR-ABL mutants in 32D myeloblast cells and found that
      binding to fibronectin is mediated primarily by the alpha5beta1 integrin. We
      performed a structure/function analysis to map domains important for cell
      adhesion. Increased adhesion was mediated by 3 domains: (1) the N-terminal coiled
      coil domain that facilitates oligomerization and F-actin localization; (2) bcr
      sequences between aa 163 to 210; and (3) F-actin localization through the C
      terminal actin-binding domain of c-abl. We compared our adhesion results with the
      ability of these mutants to cause a chronic myelogenous leukemia (CML)-like
      disease in a murine bone marrow transplantation assay and found that adhesion to
      fibronectin did not correlate with the ability of these mutants to cause CML.
      Together, our results suggest that F-actin localization may play a pivotal role
      in modulating adhesion but that it is dispensable for the development of CML.

PMID- 12791660
TI  - Antitumor effect of donor marrow graft rejection induced by recipient leukocyte
      infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical
      role for recipient-derived IFN-gamma.
AB  - Some patients lose chimerism following nonmyeloablative hematopoietic cell
      transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We
      hypothesized that host-versus-graft (HVG) alloresponses might induce antitumor
      effects against recipient tumors. We explored this question in mice by
      administering recipient leukocyte infusions (RLIs) to mixed chimeras established
      with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A
      (H2a)-->B6 (H2b) strain combination using depleting anti-T-cell monoclonal
      antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia
      cells (MMB3.19) were administered 7 days following donor lymphocyte infusion
      (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft
      versus-host disease (GVHD) following DLI, whereas RLI led to loss of chimerism.
      Both RLI and DLI significantly delayed tumor mortality. In another strain
      combination (B10.BR [H2k]-->BALB/c [H2d]), RLI-induced or spontaneous loss of
      chimerism was associated with antitumor effects against the host-type B-cell
      lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced
      elevated serum interferon-gamma (IFN-gamma) levels, and recipient-derived IFN
      gamma was critical for their antitumor effects. Thus, HVG reactions (spontaneous
      or induced by RLI) mediate antitumor effects against hematologic malignancies via
      a recipient-derived IFN-gamma-mediated mechanism. A novel approach to achieving
      anti-tumor effects without the risk of GVHD is suggested.

PMID- 12791661
TI  - A novel strategy using single-chain antibody to show the importance of Bcl-2 in
      mast cell survival.
AB  - Apoptosis or programmed cell death plays an important role in a wide variety of
      physiologic processes and is regulated by proteins of the Bcl-2 family consisting
      of both antiapoptotic and proapoptotic factors. The direct involvement of the Bcl
      2 protein family in the process of mast cell apoptosis has not been clarified. In
      the present work we have used a single-chain antibody (scFv) raised against Bcl-2
      derived from a semisynthetic human phage-display antibody library. The addition
      of TAT sequence, which is responsible for translocation through the membrane,
      endows the anti-Bcl-2-scFv with the ability to penetrate living cells. Moreover,
      it specifically neutralizes Bcl-2 intracellularly by binding to the BH1 domain
      and eradicates its antiapoptotic activity in 2 types of mast cells and in a human
      breast cancer cell line.

PMID- 12791662
TI  - Clinico-biologic features and treatment outcome of adult pro-B-ALL patients
      enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL
      fusion genes correlates with a significantly better clinical outcome.
AB  - To elucidate the biologic and clinical heterogeneity of adult pro-B acute
      lymphoblastic leukemia (ALL) (ie, terminal deoxynucletidyl-transferase
      positive[TdT+], CD19+, CD10-, surface immunoglobulin-negative [SIg-]), we
      evaluated 66 patients enrolled in the Italian multicentric Gruppo Italiano
      Malattie Ematologiche dell'Adulto (GIMEMA) 0496 study between October 1996 and
      December 1999. The ALL1/AF4 fusion transcript, originating from the t(4;11)
      translocation, was detected in 24 patients (36.4%), and the BCR/ABL chimeric
      product was found in 6 patients (9%), while the remaining 36 cases (54.6%) were
      ALL1/AF4-BCR/ABL-negative. A white blood cell (WBC) count higher than 50 x 109/L
      was found in 13 of 24, 2 of 6, and 6 of 36 of the ALL1/AF4-positive, BCR/ABL
      positive, and ALL1/AF4-BCR/AB-negative patients, respectively (P =.007). None of
      the 24 ALL1/AF4-positive patients coexpressed the CD13 and/or CD33 myeloid
      antigens. By contrast, CD13 and CD33 molecules were detected, respectively, in 3
      of 6 and in 14 of 33 cases of the BCR/ABL-positive patient group, and in 2 of 6
      and 9 of 35 cases of the ALL1/AF4-BCR/ABL-negative patient group. These
      differences still remained statistically significant even if the BCR/ABL-positive
      patients were excluded from the analysis. A complete remission (CR) was achieved
      in 52 (83.4%) of the 62 patients with ALL evaluable for response to treatment. CR
      rates were similar in the 3 genotypic groups. By contrast, comparing patients
      with or without the ALL1/AF4 gene the probability of remaining in continuous
      complete remission (CCR) at 3.5 years was 16% and 49.8%, respectively (P =.005).
      Our data demonstrate that in adult pro-B-ALL a distinction should be made between
      pro-B-ALL cases with and without the ALL1/AF4 or the BCR/ABL chimeric genes,
      since the absence of both of these fusion genes correlates with a significantly
      better clinical outcome after intensive polychemotherapy treatment without
      hematopoietic stem cell transplantation.

PMID- 12791663
TI  - Leukemia in twins: lessons in natural history.
AB  - Identical infant twins with concordant leukemia were first described in 1882, and
      since that time many such pairs of infants and older children have been
      described. It has long been recognized that this situation offers a unique
      opportunity to identify aspects of the developmental timing, natural history, and
      molecular genetics of pediatric leukemia in general. We reviewed both the older
      literature and more recent molecular biologic studies that have uncovered the
      basis of concordance of leukemia. Molecular markers of clonality, including
      unique, genomic fusion gene sequences, have provided unequivocal evidence that
      twin pairs of leukemia have a common clonal origin. The only plausible basis for
      this, first suggested more than 40 years ago, is that following initiation of
      leukemia in one twin fetus, clonal progeny spread to the co-twin via vascular
      anastomoses within a single, monochorionic placenta. This explanation has been
      endorsed by the identification of clonotypic gene fusion sequences in archived
      neonatal blood spots of individuals who subsequently developed leukemia. These
      analyses of twin leukemias have thrown considerable light on the natural history
      of disease. They reveal a frequent prenatal origin and an early or initiating
      role for chromosome translocations. Further, they provide evidence for a variable
      and often protracted latency and the need, in childhood acute lymphoblastic
      leukemia (ALL)/acute myeloblastic leukemia (AML), for further postnatal exposures
      and/or genetic events to produce clinical disease. We argue that these insights
      provide a very useful framework for attempts to understand etiologic mechanisms.

PMID- 12791664
TI  - Filamin A binding to the cytoplasmic tail of glycoprotein Ibalpha regulates von
      Willebrand factor-induced platelet activation.
AB  - We examined the hypothesis that filamin A binding to the cytoplasmic tail of
      platelet glycoprotein Ibalpha (GpIbalpha) is regulated by pathologic shear stress
      and modulates von Willebrand factor (VWF)-induced platelet activation. To begin,
      we examined filamin binding to GpIbalpha in Chinese hamster ovary cells
      coexpressing mutant human GpIb-IX and wild-type human filamin A. We observed that
      many different deletions and truncations N-terminal to GpIbalpha's cytoplasmic
      domain residue 594 disrupted filamin A binding, but that binding was unaffected
      by 14 different point mutations in hydrophilic residues between amino acids 557
      and 593. To try to narrow GpIbalpha's filamin A-binding domain, we next measured
      the effect of several cytoplasmic domain peptides on human filamin A binding to a
      GST-GpIbalpha cytoplasmic domain fusion protein. One peptide (residues 557-575;
      designated "A4 peptide") inhibited filamin A binding to the GST-GpIbalpha
      cytoplasmic domain fusion protein and competed with GpIbalpha for binding to
      filamin A. When the A4 peptide was delivered to intact human platelets using a
      carrier peptide, we observed the dose-dependent inhibition of VWF-induced
      platelet aggregation in response to both ristocetin and shear stress. The effect
      of the A4 peptide on shear-induced platelet aggregation was accompanied by the
      attenuation of shear-induced filamin A binding to GpIbalpha and diminished shear
      dependent protein tyrosine phosphorylation. These results suggest that shear
      dependent VWF-induced platelet activation affects filamin A binding to GpIb-IX-V,
      and that filamin A binding to the cytoplasmic tail of GpIbalpha regulates
      proaggregatory tyrosine kinase signaling.

PMID- 12791665
TI  - T-cell developmental blockage by tachykinin antagonists and the role of hemokinin
      1 in T lymphopoiesis.
AB  - Hemokinin 1 (HK-1) is a new member of the tachykinin peptide family that is
      expressed in hematopoietic cells. Recent reports studying mouse, rat, and human
      orthologs of HK-1 demonstrate a broader distribution than originally reported.
      Our previous studies demonstrated that HK-1, by promoting proliferation,
      survival, and possibly maturation of B-cell precursors, plays an important role
      in B lymphopoiesis. Here we present data showing that HK-1 also influences T-cell
      development at a similar stage of differentiation. This peptide enhanced the
      proliferation of T-cell precursors and increased the number of thymocytes in
      fetal thymus organ cultures (FTOCs). Tachykinin antagonists, on the other hand,
      greatly reduced the cellularity of thymi both in vivo and in vitro. The major
      reduction occurred in the CD4/CD8 double-positive (DP) cells and the CD44-CD25+
      subset of the CD4/CD8 double-negative (DN) cells. Of note, these populations also
      express HK-1, raising the possibility of autocrine or paracrine pathways
      influencing T-cell development as we previously reported for B-cell development.
      Consistent with this, the detrimental effect of tachykinin antagonists could be
      partially overcome with exogenous HK-1 peptide.

PMID- 12791666
TI  - Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on
      human microvascular endothelial cells.
AB  - Stimulation of vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) increases the expression of CXCR4 on endothelial cells,
      rendering these cells more responsive to stromal-derived factor 1 (SDF-1), an
      angiogenic CXC chemokine and unique ligand for CXCR4. Here, we show that
      prostaglandin E2 (PGE2) mediates the effects of bFGF and VEGF in up-regulating
      CXCR4 expression on human microvascular endothelial cells (HMECs). Forskolin or 3
      isobutyl-1-methyl xanthine (IBMX), 2 inducers of adenylate cyclase, markedly
      enhanced, whereas cyclooxygenase (COX) inhibitors including aspirin, piroxicam,
      and NS398 markedly inhibited CXCR4 expression on HMECs. Furthermore, the ability
      of PGE2 to augment in vitro tubular formation in SDF-1alpha containing matrigel
      was inhibited completely by blocking CXCR4. Treatment of bFGF- or VEGF-stimulated
      HMECs with COX inhibitors blocked tubular formation by about 50% to 70%.
      Prostaglandin-induced human endothelial cell organization and subsequent
      vascularization can be inhibited to a greater extent by a neutralizing antibody
      to human CXCR4 in severe combined immunodeficient mice. Additionally, VEGF- and
      bFGF-induced angiogenesis in vivo was also inhibited by about 50% by NS-398 or
      piroxicam, and this inhibitory effect was accompanied by decreased expression of
      CXCR4 on murine endothelial cells. Consequently, by inducing CXCR4 expression,
      prostaglandin accounts for about 50% of the tubular formation in vitro and in
      vivo angiogenic effects of VEGF and bFGF. Moreover, augmentation of CXCR4
      expression by VEGF, bFGF, and PGE2 involves stimulation of transcription factors
      binding to the Sp1-binding sites within the promoter region of the CXCR4 gene.
      These findings indicate that PGE2 is a mediator of VEGF- and bFGF-induced CXCR4
      dependent neovessel assembly in vivo and show that angiogenic effects of PGE2
      require CXCR4 expression.

PMID- 12791667
TI  - A new xenograft model for graft-versus-host disease by intravenous transfer of
      human peripheral blood mononuclear cells in RAG2-/- gammac-/- double-mutant mice.
AB  - The safe application of new strategies for the treatment of graft-versus-host
      disease (GVHD) is hampered by the lack of a clinically relevant model for
      preclinical testing. Current models are based on intraperitoneal transfer of
      human peripheral blood mononuclear cells (huPBMCs) into NOD-SCID (nonobese
      diabetic-severe combined immunodeficient)/SCID mice. Intravenous transfer would
      be preferred but this has always been ineffective. We developed a new model for
      xenogeneic GVHD (X-GVHD) by intravenous transfer of huPBMCs into RAG2-/- gammac-/
      mice. Our results show a high human T-cell chimerism of more than 20% (up to 98%)
      in more than 90% of mice, associated with a consistent development of XGVHD
      within 14 to 28 days and a total mortality rate of 85% shorter than 2 months.
      After murine macrophage depletion, engraftment was earlier and equally high with
      lower doses of huPBMCs. Human macrophages were also absent in these mice.
      Purified huCD3+ cells showed a similar X-GVH effect with contribution of both CD4
      and CD8 phenotypes. Human immunoglobulins and cytokines were produced in diseased
      mice. One of 30 mice developed chronic X-GVHD with skin histology similar to
      human GVHD. In conclusion, we present a new model for X-GVHD by intravenous
      transfer of huPBMCs in RAG2-/- gammac-/- mice. Murine and human macrophages do
      not seem to be necessary for acute X-GVHD in this model.

PMID- 12791668
TI  - CD8+ T cells that express CD4 on their surface (CD4dimCD8bright T cells)
      recognize an antigen-specific target, are detected in vivo, and can be
      productively infected by T-tropic HIV.
AB  - CD4 can be up-regulated on CD8+ T cells generating a CD4dimCD8bright phenotype.
      We previously demonstrated that the CD4dimCD8bright phenotype constitutes an
      activated phenotype of CD8+ T cells. We demonstrate here that the activated
      CD4dimCD8bright T cells are not undergoing apoptosis and do not produce
      significant intracellular levels of interferon gamma (IFNgamma), interleukin 2
      (IL-2), or IL-10 but express elevated levels of intracellular IL-4 in comparison
      to CD8+CD4- and CD4+ T cells. In response to cytomegalovirus (CMV) peptide (pp65)
      priming, CD4dimCD8bright cells recognized CMV pp65 tetramer approximately 19-fold
      higher than CD4-CD8+ T cells, indicating that these cells are capable of antigen
      specific recognition to a far greater extent than CD4-CD8+ T cells.
      CD4dimCD8bright T cells also express both CXCR4 and CCR5 but are susceptible to T
      tropic and not M-tropic HIV infection. A soluble factor believed to be beta
      chemokine is responsible for the inhibition of M-tropic HIV infection in
      CD4dimCD8bright T cells. CD8+ T cells from HIV+ patients were capable of up
      regulating CD4 on CD8+ T cells. We also provide evidence of the presence of
      peripheral blood CD4dimCD8bright T cells in HIV+ patients, albeit at low
      frequency. Collectively, these data suggest a role of CD4dimCD8bright T cells in
      both normal T-cell biology and HIV pathogenesis.

PMID- 12791669
TI  - Enzymatically catalyzed disulfide exchange is required for platelet adhesion to
      collagen via integrin alpha2beta1.
AB  - Integrin alpha2beta1 is the principal adhesive receptor for collagen but
      platelets also adhere through glycoprotein VI (GPVI). Integrin alphaIIbbeta3 may
      augment platelet adhesion. We have shown that disulfide exchange is necessary for
      platelet adhesion to fibrinogen, fibronectin, and collagen. However 2 questions
      remained: (1) Can activated alphaIIbbeta3 explain the observed role of disulfide
      exchange in adhesion to collagen, or is this role common to other integrins? (2)
      Is disulfide dependence specific to the integrin receptors or shared with GPVI?
      To discriminate adhesive functions of alpha2beta1 from those of alphaIIbbeta3 we
      used Glanzmann platelets and alphaIIbbeta3-specific antibodies applied to normal
      platelets. To resolve adhesive events mediated by alpha2beta1 from those of GPVI
      we used synthetic peptides specific to each receptor. We addressed direct
      integrin ligation using purified alpha2beta1 and recombinant I domain. We
      observed the following: adhesion to the alpha2beta1-specific peptide was
      disulfide-exchange dependent and protein disulfide isomerase (PDI) mediated;
      membrane-impermeant thiol blockers inhibited alpha2beta1, but not GPVI mediated,
      adhesion; direct blockade of PDI revealed that it is involved in adhesion through
      alpha2beta1 but not GPVI; and purified alpha2beta1, but not recombinant I domain,
      depended on free thiols for ligation. These data suggest that the enzymatically
      catalyzed adhesion-associated reorganization of disulfide bonds is common to
      members of the integrin family and specific to this family.

PMID- 12791670
TI  - Genetic background selectively influences innominate artery atherosclerosis:
      immune system deficiency as a probe.
AB  - OBJECTIVE: We sought to examine whether there is a site-specific effect on
      atherosclerosis of the absence of mature T and B cells caused by a recombination
      activating-gene deficiency in LDL receptor-deficient mice and whether this effect
      is influence by the extent of backcrossing to C57BL/6 mice. METHODS AND RESULTS:
      Male mice were fed atherogenic diets for 3 months. In strain 1 mice, in which
      approximately 93% of the genes were from C57BL/6 mice, the absence of mature T
      and B cells led to a significant reduction in atherosclerosis in both the aortic
      sinus and the innominate artery. In strain 2 mice, in which approximately 99+% of
      the genes were from C57BL/6 mice, immune system deficiency led to a site-specific
      effect on atherosclerosis, with a reduction in atherosclerosis in the aortic
      sinus but not in the innominate artery, similar to previous results obtained with
      apolipoprotein E-/- mice. All of the immune system-incompetent mice had lower
      plasma total and VLDL cholesterol levels regardless of strain or diet, indicating
      that differences in lipid levels were unlikely to be responsible for these site
      specific effects of immune system deficiency. CONCLUSIONS: These results suggest
      that immune system deficiency has a site-specific effect on atherosclerosis that
      is sensitive to the genetic background of the mice.

PMID- 12791671
TI  - Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells
      by shear stress in human vessels with intact endothelium.
AB  - OBJECTIVE: We investigated the role of shear stress in regulating P2 receptors in
      human umbilical vein. METHODS AND RESULTS: Using a novel, computerized,
      biomechanical perfusion model, parallel vessel segments were randomized to
      simultaneous perfusion under high (25 dyn/cm2) or low (<4 dyn/cm2) shear stress
      at identical mean perfusion pressure (20 mm Hg) for 6 hours. In the endothelium,
      no significant P2 receptor mRNA differences were found. In smooth muscle cells
      (SMCs), high shear stress decreased P2X1 receptors, whereas P2Y2 and P2Y6
      receptors were upregulated. These findings were consistent at the mRNA level
      (real-time reverse transcription-polymerase chain reaction), protein level
      (Western blot), and morphologically (immunohistochemistry). The changes were more
      pronounced in the subintimal layer of the media. CONCLUSIONS: Our findings
      suggest that shear stress might regulate gene expression in SMCs more than in the
      endothelium in intact vessels. Decreased expression of the contractile P2X1
      receptor could lead to reduced vascular tonus and increased blood flow. Because
      P2Y2 and P2Y6 receptors stimulate growth and migration of SMCs, increased
      expression of these receptors could promote vascular remodeling induced by shear
      stress. The pattern of upregulation of mitogenic P2Y receptors and downregulation
      of contractile P2X1 receptor is similar to changes seen in the phenotypic shift
      from contractile to synthetic SMCs.

PMID- 12791672
TI  - Association of high coronary heart disease risk status with circulating oxidized
      LDL in the well-functioning elderly: findings from the Health, Aging, and Body
      Composition study.
AB  - OBJECTIVE: Although circulating oxidized LDL (oxLDL) is elevated in persons with
      coronary heart disease (CHD), whether oxLDL is elevated in persons with high CHD
      risk before any events is unknown. Therefore, we studied the association between
      high, predicted CHD risk and oxLDL in the Health ABC cohort. METHODS AND RESULTS:
      This cohort included 385 persons with CHD and 1183 persons at high risk; the
      latter were all persons with CHD risk equivalents: noncoronary forms of clinical
      atherosclerotic disease, diabetes, and a 10-year risk for CHD >20% by Framingham
      scoring. The remaining 1535 participants were at low risk. Levels of oxLDL were
      1.18+/-0.61 mg/dL for low-risk persons, 1.50+/-0.81 mg/dL for high-risk persons
      without diagnosed CHD, and 1.32+/-0.83 mg/dL for persons with CHD (P<0.001). The
      odds ratio for high CHD risk in the highest quintile of oxLDL, compared with the
      lowest quintile and after adjusting for age, sex, race, LDL cholesterol, smoking
      status, and C-reactive protein, was 2.79 (P<0.001). CONCLUSIONS: The odds ratio
      for elevated oxLDL among persons with high CHD risk before any CHD events was
      higher than that among persons with established CHD. A likely explanation is that
      once CHD is diagnosed, individuals are frequently treated with a statin, which is
      associated with lowering of LDL cholesterol and oxLDL levels.

PMID- 12791673
TI  - High methionine and cholesterol diet abolishes endothelial relaxation.
AB  - OBJECTIVE: High plasma cholesterol or homocysteine is a risk factor for
      atherosclerosis. Cholesterol and methionine, the precursor of homocysteine, are
      rarely eaten separately. Thus, the aims of this study were to determine neointima
      formation, aortic reactivity, and factors involved in endothelial function in
      rabbits fed high dietary cholesterol, methionine, or a combination of the two for
      12 weeks. METHODS AND RESULTS: Rabbit dietary groups were randomized into the
      following: control (Con), 0.5% cholesterol (Chol), 1% methionine (Meth), and 1%
      methionine+0.5% cholesterol (MethChol). Aortic reactivity was studied by
      isometric tension techniques, aortic volumetric analysis was determined by
      stereological techniques, and immunohistochemistry was used to localize
      endothelial and inducible NO synthases, superoxide dismutase, macrophages, and
      nitrotyrosine. Atherosclerosis was present in the Chol and MethChol groups.
      Endothelium-dependent relaxation was virtually abolished in the MethChol group
      compared with control. Such decrease in relaxation was not attributable to a
      vascular smooth muscle cell defect or to a decrease in endothelial NO synthase or
      superoxide dismutase content. Macrophages and inducible NO synthase
      immunoreactivity were present in Chol and MetChol groups. CONCLUSIONS: The
      combination of high dietary cholesterol plus methionine virtually abolishes
      endothelium-dependent relaxation, underscoring the importance of multiple risk
      factors in the development of cardiovascular disease.

PMID- 12791674
TI  - Cholesteryl ester transfer protein expression prevents diet-induced
      atherosclerotic lesions in male db/db mice.
AB  - OBJECTIVE: Accompanying more atherogenic lipoprotein profiles and an increased
      incidence of atherosclerosis, plasma cholesteryl ester transfer protein (CETP) is
      depressed in diabetic obese patients compared with nondiabetic obese
      counterparts. The depressed levels of CETP in the plasma of diabetic obese
      individuals may contribute to the development of an atherogenic lipoprotein
      profile and atherogenesis. We have examined the effect of CETP expression on
      vascular health in the db/db model of diabetic obesity. METHODS AND RESULTS:
      Transgenic mice expressing the human CETP minigene were crossed with db/db
      strain, and 3 groups of offspring (CETP, db, and db/CETP) were placed on an
      atherogenic diet for 16 weeks. The proximal aorta was then excised and examined
      for the presence of atherosclerotic plaques. In db mice, 9 of 11 had intimal
      lesions with a mean area of 26 098+/-7486 microm2. No lesions greater than 1000
      microm2 were observed in db/CETP or CETP mice. CETP-expressing mice had lower
      circulating cholesterol concentrations than db mice. Fractionating plasma lipids
      by FPLC indicated that the difference in total cholesterol was primarily
      attributable to differences in VLDL and LDL. CONCLUSIONS: The expression of human
      CETP in db/db mice prevented the formation of diet-induced lesions, suggesting an
      antiatherogenic effect of CETP in the context of diabetic obesity.

PMID- 12791675
TI  - Neurotrophin and neurotrophin receptor protein expression in the human lung.
AB  - Neurotrophins (NTs) promote survival and differentiation of central and
      peripheral neurons, and display several activities also in non-neuronal cells.
      Human lungs synthesize and release NTs, which are probably involved in the
      pathophysiology of pulmonary disturbances. In this article the expression and
      anatomic localization of nerve growth factor, brain-derived neurotrophic factor,
      and NT-3 and of corresponding high-affinity receptors TrkA, TrkB (full-length and
      truncated [TR-] isoforms), TrkC, and of the low-affinity p75 receptor, were
      assessed in surgical samples from adult human lung by reverse transcriptase
      polymerase chain reaction, Western blot, and immunohistochemistry. NTs and their
      cognate receptor mRNA and protein transcripts were detected by reverse
      transcriptase-polymerase chain reaction and immunoblotting, respectively, nerve
      growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA and
      corresponding protein transcripts being the most expressed. High levels of TrkB
      [TR-] mRNA and of its protein transcript were also demonstrated, whereas a low
      expression of p75 mRNA and of corresponding protein transcript were found.
      Microanatomic analysis of immunohistochemical study revealed that bronchial
      epithelial cells were immunoreactive for different NTs, with a higher intensity
      of BDNF immune staining compared with other NTs, but did not express NT receptor
      immunoreactivity. Alveolar cells were immunoreactive for TrkA and TrkC receptor
      protein, but did not display immunoreactivity for NTs or other receptors
      investigated. Gland cells expressed NT and high-affinity NT receptor
      immunoreactivity, but not p75 receptor immunoreactivity. NT and low-affinity
      receptor immunoreactivity was observed within neurons and satellite cells of
      parasympathetic ganglia as well as in nerve fiber-like structures supplying the
      bronchopulmonary tree. An obvious immunoreactivity for NTs and NT receptor
      protein was also observed in intrapulmonary branches of pulmonary artery.
      Pulmonary lymphocytes and macrophages express nerve growth factor and high
      affinity NT receptor immunoreactivity. The role of NTs in non-neuronal tissue
      including lung has not been clarified yet. The widespread expression of NTs and
      their receptors in different components of the lung suggests that these factors
      may contribute to regulate cell function in human lung.

PMID- 12791676
TI  - Effects of mitochondrial inhibitors and uncouplers on hypoxic vasoconstriction in
      rabbit lungs.
AB  - Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion to ventilation
      for optimizing pulmonary gas exchange; however, the underlying mechanism has not
      yet been fully elucidated. Lung nitric oxide (NO) generation appears to be
      involved in this process. Recently, mitochondria have been proposed as oxygen
      sensors, with HPV signaling via a hypoxia-induced increase in the generation of
      reactive oxygen species derived from mitochondrial complex III and escaping
      through an anion channel into the cytoplasm. In addition, complex II has been
      suggested to be specifically involved in hypoxia-dependent generation of reactive
      oxygen species in the lung. We investigated the effects of several mitochondrial
      inhibitors and uncouplers on the strength of HPV, and asked for their capacity to
      mimic HPV during normoxia in isolated buffer-perfused rabbit lungs. Specificity
      of the agents for HPV was tested by comparison of their effects on non-hypoxia
      induced vasoconstriction, elicited by the thromboxane mimetic U46619.
      Interference with NO metabolism was determined by performing parallel studies
      with blocked lung NO generation and by measurement of exhaled NO. Rotenone, 3
      nitroproprionic acid, and myxothiazol dose-dependently inhibited HPV without
      being mimics of HPV during normoxia. The inhibitory effect of these agents was
      only partly specific for HPV by comparison with U46619-induced vasoconstriction.
      During pre-blocked lung NO synthesis, the selectivity for HPV inhibition was
      increased for rotenone, but largely lost for myxothiazol. 2
      tenoyltrifluoroacetone resulted in an unspecific inhibition of HPV as compared
      with U46619-induced vasoconstriction. 1-methyl-4-phenylpyridinium iodide and 2
      heptyl-4-hydroxyquinoline-N-oxide specifically suppressed HPV and increased
      normoxic vascular tone. Antimycin A suppressed HPV, an effect being specific in
      lungs with intact NO synthesis and only partly specific while blocking NO.
      However, this agent did not mimic HPV during normoxia, as may be expected for
      interference with the mitochondrial electron transport downstream in complex III.
      The uncouplers 2,4-dinitrophenol (DNP, 10-200 microM) and carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone (FCCP, 1-3 microM) induced sustained
      vasoconstriction during normoxia, with enhancement of HPV by DNP at low and
      suppression of HPV for both agents at high concentrations. The anion channel
      blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid inhibited HPV and
      U46619-induced vasoconstriction with identical dose-response curves. These
      findings suggest that mitochondria are in some manner involved in the regulation
      of HPV in intact rabbit lungs. The hypothesis that enhanced superoxide leak at
      complex III of mitochondria represents the underlying mechanism of acute HPV is
      supported by the rotenone and 2-heptyl-4-hydroxyquinoline-N-oxide data, but
      partly contradicted by the findings with 1-methyl-4-phenylpyridinium iodide,
      antimycin A, DNP, and FCCP. Further studies are mandatory to clarify the link
      between mitochondrial respiratory chain and hypoxic pulmonary vasoconstriction.

PMID- 12791677
TI  - Proapoptotic effects of parathyroid hormone-related protein in type II
      pneumocytes.
AB  - Parathyroid hormone-related protein (PTHrP) promotes or suppresses apoptosis in
      various settings depending on cell type and context. PTHrP 1-34 and PTHrP 67-86
      are type II cell growth factors with effects on pneumocyte growth and surfactant
      secretion. This study investigated the effects of 24 h pretreatment with these
      two peptides on rat type II cell apoptosis after 0.3 J/cm2 ultraviolet-B
      irradiation. Adherent cells decreased in number by 15 +/- 5% and nonadherent
      cells increased > 5-fold 24 h after ultraviolet irradiation. Cell loss was due
      predominantly to apoptosis, based on ethidium bromide exclusion, nuclear
      condensation, and caspase 3 activity. Nuclear condensation increased from 15.6 +/
      2.2% of irradiated cells with no treatment to 25.6 +/- 4.9 and 22.9 +/- 1.8% of
      cells in ultraviolet/PTHrP 1-34 and ultraviolet/PTHrP 67-86 groups, respectively
      (P < 0.01), along with a 60% increase in caspase 3 activity. Effects on apoptosis
      were unaffected by the presence or absence of serum, but were ameliorated by
      growth to confluence or adherence to fibronectin. PTHrP 1-34 and PTHrP 67-86
      augmented inositol phosphate levels, but had minimal effects on cAMP. Thus, PTHrP
      1-34 and PTHrP 67-86 sensitize type II cells to apoptosis, possibly by a
      phospholipase C-dependent mechanism. The effects appear to be regulated by cell
      matrix and cell-cell interactions.

PMID- 12791678
TI  - Superoxide-dependent iron uptake: a new role for anion exchange protein 2.
AB  - Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by
      incompletely understood mechanisms. We tested the hypothesis that human bronchial
      epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide
      dependent ferri-reductase activity involving anion exchange protein 2 (AE2) and
      extracellular bicarbonate (HCO3-). HBE cells that constitutively express AE2 mRNA
      by reverse transcriptase-polymerase chain reaction and AE2 protein by Western
      analysis avidly transported NTBI after exposure to either Fe2+ or Fe3+, but
      reduction of Fe3+ to Fe2+ was first required. The ability of HBE cells to reduce
      Fe3+ and transport Fe2+ was inhibited by active extracellular superoxide
      dismutase (SOD). Similarly, HBE cells that overexpress Cu,Zn SOD after adenoviral
      infection with AdSOD1 showed diminished iron uptake. The role of AE2 in iron
      uptake was indicated by three lines of evidence: (i) lack of both iron reduction
      and iron transport in bicarbonate-free buffer at controlled pH, (ii) failure of
      HBE cells treated with stilbene AE inhibitors to reduce Fe3+ or transport iron,
      and (iii) inhibition of iron uptake in HBE cells by inhibition of AE2 protein
      expression with antisense oligonucleotides. We thus disclose a novel ferri
      reductase mechanism of NTBI uptake by human lung cells that employs superoxide
      exchange for HCO3- by AE2 protein in the plasma membrane.

PMID- 12791679
TI  - Discovery of DNA polymerase.

PMID- 12791680
TI  - Interaction of nucleoplasmin with core histones.
AB  - Nucleoplasmin is one of the most abundant proteins in Xenopus laevis oocytes, and
      it has been involved in the chromatin remodeling that takes place immediately
      after fertilization. This molecule has been shown to be responsible for the
      removal of the sperm-specific proteins and deposition of somatic histones onto
      the male pronuclear chromatin. To better understand the latter process, we have
      used sedimentation velocity, sedimentation equilibrium, and sucrose gradient
      fractionation analysis to show that the pentameric form of nucleoplasmin binds to
      a histone octamer equivalent consisting of equal amounts of the four core
      histones, H2A, H2B, H3, and H4, without any noticeable preference for any of
      these proteins. Removal of the histone N-terminal "tail" domains or the major C
      terminal polyglutamic tracts of nucleoplasmin did not alter these binding
      properties. These results indicate that interactions other than those
      electrostatic in nature (likely hydrophobic) also play a critical role in the
      formation of the complex between the negatively charged nucleoplasmin and
      positively charged histones. Although the association of histones with
      nucleoplasmin may involve some ionic interactions, the interaction process is not
      electrostatically driven.

PMID- 12791681
TI  - The minimal structural domains required for neural cell adhesion molecule
      polysialylation by PST/ST8Sia IV and STX/ST8Sia II.
AB  - A limited number of mammalian proteins are modified by polysialic acid, with the
      neural cell adhesion molecule (NCAM) being the most abundant of these. We
      hypothesize that polysialylation is a protein-specific glycosylation event and
      that an initial protein-protein interaction between polysialyltransferases and
      glycoprotein substrates mediates this specificity. To evaluate the regions of
      NCAM required for recognition and polysialylation by PST/ST8Sia IV and STX/ST8Sia
      II, a series of domain deletion proteins were generated, co-expressed with each
      enzyme, and their polysialylation analyzed. A protein consisting of the fifth
      immunoglobulin-like domain (Ig5), which contains the reported sites of
      polysialylation, and the first fibronectin type III repeat (FN1) was
      polysialylated by both enzymes, whereas a protein consisting of Ig5 alone was not
      polysialylated by either enzyme. This demonstrates that the Ig5 domain of NCAM
      and FN1 are sufficient for polysialylation, and suggests that the FN1 may
      constitute an enzyme recognition and docking site. Two other NCAM mutants, NCAM-6
      (Ig1-5) and NCAM-7 (FN1-FN2), were weakly polysialylated by PST/ST8Sia IV,
      suggesting that a weaker enzyme recognition site may exist within the Ig domains,
      and that glycans in the FN region are polysialylated. Further analysis indicated
      that O-linked oligosaccharides in NCAM-7, and O-linked and N-linked glycans in
      full-length NCAM, are polysialylated when these proteins are co-expressed with
      the polysialyltransferases in COS-1 cells. Our data support a model in which the
      polysialyltransferases bind to the FN1 of NCAM to polymerize polysialic acid
      chains on appropriately presented glycans in adjacent regions.

PMID- 12791682
TI  - Cleavage of von Willebrand factor requires the spacer domain of the
      metalloprotease ADAMTS13.
AB  - ADAMTS13 consists of a reprolysin-type metalloprotease domain followed by a
      disintegrin domain, a thrombospondin type 1 motif (TSP1), Cys-rich and spacer
      domains, seven more TSP1 motifs, and two CUB domains. ADAMTS13 limits platelet
      accumulation in microvascular thrombi by cleaving the Tyr1605-Met1606 bond in von
      Willebrand factor, and ADAMTS13 deficiency causes a lethal syndrome, thrombotic
      thrombocytopenic purpura. ADAMTS13 domains required for substrate recognition
      were localized by the characterization of recombinant deletion mutants.
      Constructs with C-terminal His6 and V5 epitopes were expressed by transient
      transfection of COS-7 cells or in a baculovirus system. No association with
      extracellular matrix or cell surface was detected for any ADAMTS13 variant by
      immunofluorescence microscopy or chemical modification. Both plasma and
      recombinant full-length ADAMTS13 cleaved von Willebrand factor subunits into two
      fragments of 176 kDa and 140 kDa. Recombinant ADAMTS13 was divalent metal ion
      dependent and was inhibited by IgG from a patient with idiopathic thrombotic
      thrombocytopenic purpura. ADAMTS13 that was truncated after the metalloprotease
      domain, the disintegrin domain, the first TSP1 repeat, or the Cys-rich domain was
      not able to cleave von Willebrand factor, whereas addition of the spacer region
      restored protease activity. Therefore, the spacer region is necessary for normal
      ADAMTS13 activity toward von Willebrand factor, and the more C-terminal TSP1 and
      CUB domains are dispensable in vitro.

PMID- 12791683
TI  - Native human TATA-binding protein simultaneously binds and bends promoter DNA
      without a slow isomerization step or TFIIB requirement.
AB  - The association of TATA-binding protein (TBP) with promoter DNA is central to the
      initiation and regulation of eukaryotic protein synthesis. Our laboratory has
      previously conducted detailed investigations of this interaction using yeast TBP
      and seven consensus and variant TATA sequences. We have now investigated this key
      interaction using human TBP and the TATA sequence from the adenovirus major late
      promoter (AdMLP). Recombinant native human protein was used together with
      fluorescently labeled DNA, allowing real time data acquisition in solution. We
      find that the wild-type hTBP-DNAAdMLP reaction is characterized by high affinity
      (Kd < or = 5 nm), simultaneous binding and DNA bending, and rapid formation of a
      stable human TBP-DNA complex having DNA bent approximately 100 degrees. These
      data allow, for the first time, a direct comparison of the reactions of the full
      length, native human and yeast TBPs with a consensus promoter, studied under
      identical conditions. The general reaction characteristics are similar for the
      human and yeast proteins, although the details differ and the hTBPwt-induced bend
      is more severe. This directly measured hTBPwt-DNAAdMLP interaction differs
      fundamentally from a recently published hTBPwt-DNAAdMLP model characterized by
      low affinity (microM) binding and an unstable complex requiring either a 30-min
      isomerization or TFIIB to achieve DNA bending. Possible sources of these
      significant differences are discussed.

PMID- 12791685
TI  - Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown
      yeast cells.
AB  - Lithium is highly toxic to yeast when grown in galactose medium mainly because
      phosphoglucomutase, a key enzyme of galactose metabolism, is inhibited. We
      studied the global protein and gene expression profiles of Saccharomyces
      cerevisiae grown in galactose in different time intervals after addition of
      lithium. These results were related to physiological studies where both secreted
      and intracellular metabolites were determined. Microarray analysis showed that
      664 open reading frames were down-regulated and 725 up-regulated in response to
      addition of lithium. Genes involved in transcription, translation, and nucleotide
      metabolism were down-regulated at the transcriptional level, whereas genes
      responsive to different stresses as well as genes from energy reserve metabolism
      and monosaccharide metabolism were up-regulated. Compared with the proteomic
      data, 26% of the down-regulated and 48% of the up-regulated proteins were also
      identified as being changed on the mRNA level. Functional clusters obtained from
      proteome data were coincident with transcriptional clusters. Physiological
      studies showed that acetate, glycerol, and glycogen accumulate in response to
      lithium, as reflected in expression data, whereas a change from respiro
      fermentative to respiratory growth could not be predicted from the expression
      analyses.

PMID- 12791684
TI  - Two functionally divergent p53-responsive elements in the rat bradykinin B2
      receptor promoter.
AB  - Although p53 is known to have dual functions as a transcriptional activator and
      repressor, there has not been an example where both p53-activating and 
      repressing elements reside within one target promoter. Previous work from this
      laboratory defined two different p53 response elements, termed P1 and P2, located
      at nucleotide positions -70 and -707, respectively, in the rat bradykinin B2
      receptor promoter. In this study, through manipulation of the DNA sequence and
      context, we demonstrate opposing roles for P1 and P2 as transcriptional activator
      and repressor, respectively. Deletion of P1 abrogates p53-mediated activation. P1
      maintains its role as an activator upon relocation to the P2 site and activates
      transcription from a heterologous promoter construct. Thus, P1 is a bona fide
      positive p53-response element. In contrast, deletion of P2 enhances P1-induced
      activation. P2 represses transcription when substituted for P1 or when relocated
      midway between P1 and P2. P2-mediated repression is sequence-dependent, because
      it is reversed to activation when P2 is substituted by the P1 or p53 consensus
      sequences. Moreover, site-directed mutagenesis that converts P2 to a higher
      affinity p53-binding site results in transcriptional activation rather than
      repression. Surprisingly, P2 strongly activates a heterologous promoter. Thus, P2
      mediated transcriptional repression is both sequence- and context-dependent.
      Investigations into the mechanisms of P2-mediated repression indicate that it is
      trichostatin-insensitive and unaffected by CBP or mutation of the minimal
      repression C-terminal domain of p53. However, gel shift assays suggest that p53
      competes with other transcriptional activators for binding to overlapping binding
      sequences within the P2 element. In conclusion, this study provides a rare
      example of a transcription factor having two divergent functional effects that
      are sequence- and context-dependent. The interplay of P1 and P2 may be important
      in the regulation of bradykinin B2 receptor gene expression in response to
      inflammatory stress and during development.

PMID- 12791686
TI  - Stimulation of the plasma membrane Na+/H+ exchanger NHE1 by sustained
      intracellular acidosis. Evidence for a novel mechanism mediated by the ERK
      pathway.
AB  - Activity of the Na+/H+ exchanger (NHE) isoform 1 (NHE1) is increased by
      intracellular acidosis through the interaction of intracellular H+ with an
      allosteric modifier site in the transport domain. Additional regulation is
      achieved via kinase-mediated modulation of the NHE1 regulatory domain. To
      determine if intracellular acidosis stimulates NHE1 activity solely by the
      allosteric mechanism, we subjected cultured neonatal rat ventricular myocytes
      (NRVM) with native NHE1 expression to intracellular acidosis (pHi approximately
      6.6) for up to 6 min by transient exposure to NH4Cl and its washout in the
      presence of NHE inhibition (by zero [Na+]o or the NHE1 inhibitor cariporide) in
      HCO3- -free medium. After the desired duration of acidosis, NHE was reactivated
      (by reintroduction of [Na+]o or removal of cariporide), and the rate of recovery
      of pHi (dpHi/dt) was measured as the index of NHE activity. Regardless of the
      method used when intracellular acidosis was sustained for > or =3 min, subsequent
      NHE activity was significantly increased (>4-fold). Similar NHE stimulatory
      effects of sustained acidosis were observed in adult rat ventricular myocytes and
      COS-7 cells. Sustained (3 min) intracellular acidosis activated several NHE1
      kinases in NRVM, in an in-gel kinase assay using as substrate a glutathione S
      transferase fusion protein of the NHE1 regulatory domain. Detailed investigation
      of ERK and its downstream effector p90RSK, two putative NHE1 kinases, revealed
      time-dependent activation of both by intracellular acidosis in NRVM. Furthermore,
      inhibition of MEK1/2 by pretreatment of NRVM with two structurally distinct
      inhibitors, PD98059 (30 microM) or UO126 (3 microM), inhibited the activation of
      ERK and p90RSK and abolished the stimulation of NHE activity by sustained (3 min)
      intracellular acidosis. Our data show that not only the extent but also the
      duration of intracellular acidosis regulates NHE1 activity and suggest that the
      stimulatory effect of sustained intracellular acidosis occurs through a novel
      mechanism mediated by activation of the ERK pathway.

PMID- 12791687
TI  - Differential phosphorylation of the signal-responsive domain of I kappa B alpha
      and I kappa B beta by I kappa B kinases.
AB  - NF-kappa B activity is regulated by its association with the inhibitory I kappa B
      proteins, among which I kappa B alpha and I kappa B beta are the most abundant. I
      kappa B proteins are widely expressed in different cells and tissues and bind to
      similar combinations of NF-kappa B proteins. The degradation of I kappa B
      proteins allows nuclear translocation of NF-kappa B and hence plays a critical
      role in NF-kappa B activation. Previous studies have demonstrated that, although
      both I kappa B proteins are phosphorylated by the same I kappa B kinase (IKK)
      complex, and their ubiquitination and degradation following phosphorylation are
      carried out by the same ubiquitination/degradation machinery, their kinetics of
      degradation are quite different. To better understand the underlying mechanism of
      the differences in degradation kinetics, we have carried out a systematic,
      comparative analysis of the ability of the IKK catalytic subunits to
      phosphorylate I kappa B alpha and I kappa B beta. We found that, whereas IKK
      alpha is a weak kinase for the N-terminal serines of both I kappa B isoforms, IKK
      beta is an efficient kinase for those residues in I kappa B alpha. However, IKK
      beta phosphorylates the N-terminal serines of I kappa B beta far less
      efficiently, thereby providing an explanation for the slower rate of degradation
      observed for I kappa B beta. Mutational analysis indicated that the regions
      around the two N-terminal serines collectively influence the relative
      phosphorylation efficiency, and no individual residue is critical. These findings
      provide the first systematic analysis of the ability of I kappa B alpha and I
      kappa B beta to serve as substrates for IKKs and help provide a possible
      explanation for the differential degradation kinetics of I kappa B alpha and I
      kappa B beta.

PMID- 12791688
TI  - Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor
      to low density membrane microdomains is necessary for GnRH signaling to ERK.
AB  - Specialized membrane microdomains known as lipid rafts are thought to contribute
      to G-protein coupled receptor (GPCR) signaling by organizing receptors and their
      cognate signaling molecules into discrete membrane domains. To determine if the
      GnRHR, an unusual member of the GPCR superfamily, partitions into lipid rafts,
      homogenates of alpha T3-1 cells expressing endogenous GnRHR or Chinese hamster
      ovary cells expressing an epitope-tagged GnRHR were fractionated through a
      sucrose gradient. We found the GnRHR and c-raf kinase constitutively localized to
      low density fractions independent of hormone treatment. Partitioning of c-raf
      kinase into lipid rafts was also observed in whole mouse pituitary glands.
      Consistent with GnRH induced phosphorylation and activation of c-raf kinase, GnRH
      treatment led to a decrease in the apparent electrophoretic mobility of c-raf
      kinase that partitioned into lipid rafts compared with unstimulated cells.
      Cholesterol depletion of alpha T3-1 cells using methyl-beta-cyclodextrin
      disrupted GnRHR but not c-raf kinase association with rafts and shifted the
      receptor into higher density fractions. Cholesterol depletion also significantly
      attenuated GnRH but not phorbol ester-mediated activation of extracellular signal
      related kinase (ERK) and c-fos gene induction. Raft localization and GnRHR
      signaling to ERK and c-Fos were rescued upon repletion of membrane cholesterol.
      Thus, the organization of the GnRHR into low density membrane microdomains
      appears critical in mediating GnRH induced intracellular signaling.

PMID- 12791689
TI  - Molecular basis for atovaquone binding to the cytochrome bc1 complex.
AB  - Atovaquone is a substituted 2-hydroxynaphthoquinone that is used therapeutically
      to treat Plasmodium falciparum malaria, Pneumocystis carinii pneumonia, and
      Toxoplasma gondii toxoplasmosis. It is thought to act on these organisms by
      inhibiting the cytochrome bc1 complex. We have examined the interaction of
      atovaquone with the bc1 complex isolated from Saccharomyces cerevisiae, a
      surrogate, nonpathogenic fungus. Atovaquone inhibits the bc1 complex
      competitively with apparent Ki = 9 nm, raises the midpoint potential of the
      Rieske iron-sulfur protein from 285 to 385 mV, and shifts the g values in the EPR
      spectrum of the Rieske center. These results indicate that atovaquone binds to
      the ubiquinol oxidation pocket of the bc1 complex, where it interacts with the
      Rieske iron-sulfur protein. A computed energy-minimized structure for atovaquone
      liganded to the yeast bc1 complex suggests that a phenylalanine at position 275
      of cytochrome b in the bovine bc1 complex, as opposed to leucine at the
      equivalent position in the yeast enzyme, is responsible for the decreased
      sensitivity of the bovine bc1 complex (Ki = 80 nm) to atovaquone. When a L275F
      mutation was introduced into the yeast cytochrome b, the sensitivity of the yeast
      enzyme to atovaquone decreased (Ki = 100 nm) with no loss in activity, confirming
      that the L275F exchange contributes to the differential sensitivity of these two
      species to atovaquone. These results provide the first molecular description of
      how atovaquone binds to the bc1 complex and explain the differential inhibition
      of the fungal versus mammalian enzymes.

PMID- 12791690
TI  - Human rhinovirus 2 2Apro recognition of eukaryotic initiation factor 4GI.
      Involvement of an exosite.
AB  - The 2A proteinase (2Apro) of human rhinovirus 2 is a cysteine proteinase with a
      unique chymotrypsin-like fold. During viral replication, 2Apro performs self
      processing by cleaving between its own N terminus and the C terminus of the
      preceding protein, VP1. Subsequently, 2Apro cleaves the two isoforms of the
      cellular protein, eukaryotic initiation factor (eIF) 4G. We have previously shown
      that HRV2 2Apro can directly bind to eIF4G isoforms. Here we demonstrate using
      deletion mutants of eIF4GI that HRV2 2Apro requires eIF4GI amino acids 600-674
      for binding; however, the amino acids at the cleavage site, Arg681 downward arrow
      Gly, are not required. The HRV2 2Apro binding domain for eIF4GI was identified by
      site-directed mutagenesis. Specifically, mutations Leu17 --> Arg and Asp35 -->
      Glu severely impaired HRV2 2Apro binding and thus processing of eIF4GI in rabbit
      reticulocyte lysates; self-processing, however, was not affected. Alanine
      scanning analysis further identified the loop containing residues Tyr32, Ser33,
      and Ser34 as important for eIF4GI binding. Although Asp35 is part of the
      catalytic triad, most of the eIF4GI binding domain lies in a unique exosite
      structure absent from other chymotrypsin-like enzymes and is distinct from the
      substrate binding cleft. The exosite represents a novel virulence determinant
      that may allow the development of specific inhibitors for HRV2 2Apro.

PMID- 12791691
TI  - Effect of mutations in the C-terminal domain of Mu B on DNA binding and
      interactions with Mu A transposase.
AB  - Bacteriophage Mu transposition requires two phage-encoded proteins, the
      transposase, Mu A, and an accessory protein, Mu B. Mu B is an ATP-dependent DNA
      binding protein that is required for target capture and target immunity and is an
      allosteric activator of transpososome function. The recent NMR structure of the C
      terminal domain of Mu B (Mu B223-312) revealed that there is a patch of
      positively charged residues on the solvent-exposed surface. This patch may be
      responsible for the nonspecific DNA binding activity displayed by the purified Mu
      B223-312 peptide. We show that mutations of three lysine residues within this
      patch completely abolish nonspecific DNA binding of the C-terminal peptide (Mu
      B223- 312). To determine how this DNA binding activity affects transposition we
      mutated these lysine residues in the full-length protein. The full-length protein
      carrying all three mutations was deficient in both strand transfer and allosteric
      activation of transpososome function but retained ATPase activity. Peptide
      binding studies also revealed that this patch of basic residues within the C
      terminal domain of Mu B is within a region of the protein that interacts directly
      with Mu A. Thus, we conclude that this protein segment contributes to both DNA
      binding and protein-protein contacts with the Mu transposase.

PMID- 12791692
TI  - Modulation of 5-HT3 receptor-mediated response and trafficking by activation of
      protein kinase C.
AB  - Modulation of neurotransmitter-gated membrane ion channels by protein kinase C
      (PKC) has been the subject of a number of studies. However, less is known about
      PKC modulation of the serotonin type 3 (5-HT3) receptor, a ligand-gated membrane
      ion channel that can mediate fast synaptic transmission in the central and
      peripheral nervous system. Here, we show that PKC potentiated 5-HT3 receptor
      mediated current in Xenopus oocytes expressing 5-HT3A receptors and mouse N1E-115
      neuroblastoma cells. In addition, using a specific antibody directed to the
      extracellular N-terminal domain of the 5-HT3A receptor, treatment with the PKC
      activator, 4 beta-phorbol 12-myristate 13-acetate (PMA), significantly increased
      surface immunofluorescence. PKC also increased the amount of 5-HT3A receptor
      protein in the cell membrane without affecting the amount receptor protein in the
      total cell extract. The magnitude of PMA potentiation of 5-HT3A receptor-mediated
      responses is correlated with the magnitude of PMA enhancement of the receptor
      abundance in the cell surface membrane. PMA potentiation is unlikely to occur via
      direct phosphorylation of the 5-HT3A receptor protein since the potentiation was
      not affected by point mutation of each of the putative sites for PKC
      phosphorylation. However, preapplication of phalloidin, which stabilizes the
      actin polymerization, significantly inhibited PMA potentiation of 5-HT-activated
      responses in both N1E-115 cells and oocytes expressing 5-HT3A receptors. On the
      other hand, latrunculin-A, which destabilizes actin cytoskeleton, enhanced the
      PMA potentiation of 5-HT3A receptors. The observations suggest that PKC can
      modulate 5-HT3A receptor function and trafficking through an F-actin-dependent
      mechanism.

PMID- 12791693
TI  - Characterization of YopT effects on Rho GTPases in Yersinia enterocolitica
      infected cells.
AB  - Pathogenic yersiniae employ a type III secretion system for translocating up to
      six effector proteins (Yersinia outer proteins (Yops)) into eukaryotic target
      cells. YopT is a cysteine protease that was shown to remove the C-terminal
      isoprenoid group of RhoA, Rac, and CDC42Hs. Here we characterized the cell
      biological and biochemical activities of YopT in cells infected with pathogenic
      Yersinia enterocolitica. Bacterially injected YopT located to cell membranes from
      which it released RhoA but not Rac or CDC42Hs. In the infected cells RhoA was
      dissociated from guanine nucleotide dissociation inhibitor-1 (GDI-1) and
      accumulated as a monomeric protein in the cytosol, whereas Rac and CDC42Hs
      remained GDI-bound. Direct transfer of isoprenylated RhoA to YopT and RhoA
      modification could be reconstituted in vitro by guanosine 5'-3-O
      (thio)triphosphate loading of a recombinant RhoA.GDI-1 complex. Finally, in
      macrophages infected with a Yersinia strain selectively translocating YopT
      podosomal adhesion structures required for chemotaxis as well as phagocytic cups
      mediating uptake of yersiniae were disrupted. These findings indicate that
      bacterially translocated YopT acts on membrane-bound and GDI-complexed RhoA but
      not Rac or CDC42, and this is sufficient for disruption of macrophage immune
      functions.

PMID- 12791694
TI  - Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H)
      and NADP(H) underline the importance of nucleotide conformational changes in
      coupling to proton translocation.
AB  - Transhydrogenase couples the reduction of NADP+ by NADH to inward proton
      translocation across mitochondrial and bacterial membranes. The coupling
      reactions occur within the protein by long distance conformational changes. In
      intact transhydrogenase and in complexes formed from the isolated, nucleotide
      binding components, thio-NADP(H) is a good analogue for NADP(H), but thio-NAD(H)
      is a poor analogue for NAD(H). Crystal structures of the nucleotide-binding
      components show that the twists of the 3-carbothiamide groups of thio-NADP+ and
      of thio-NAD+ (relative to the planes of the pyridine rings), which are defined by
      the dihedral, Xam, are altered relative to the twists of the 3-carboxamide groups
      of the physiological nucleotides. The finding that thio-NADP+ is a good substrate
      despite an increased Xam value shows that approach of the NADH prior to hydride
      transfer is not obstructed by the S atom in the analogue. That thio-NAD(H) is a
      poor substrate appears to be the result of failure in the conformational change
      that establishes the ground state for hydride transfer. This might be a
      consequence of restricted rotation of the 3-carbothiamide group during the
      conformational change.

PMID- 12791695
TI  - Epiplakin gene analysis in mouse reveals a single exon encoding a 725-kDa protein
      with expression restricted to epithelial tissues.
AB  - Based on cDNA cloning and sequencing, human epiplakin has been classified as a
      member of the plakin protein family of cytolinkers. We report here the
      characterization of the mouse epiplakin gene locus and the isolation of full
      length mouse epiplakin cDNA using BAC vectors. We found that the protein is
      encoded by a single remarkably large exon (>20 kb) that consists of a series of
      0.8-1.5-kb-long DNA repeats, eight of which are virtually identical.
      Consequently, mouse epiplakin contains 16 plakin repeat domains, three more than
      reported for the human protein and eight more than predicted for the mouse
      protein based on the contig characterized by the Mouse Genome Sequencing
      Consortium. Using antibodies raised to a highly conserved repeating epiplakin
      sequence domain, we show that the protein in cells is expressed in its full
      length (725 kDa), and we provide evidence that the size of human epiplakin
      previously may have been underestimated. In addition we show on transcript and
      protein levels that epiplakin is restricted to epithelial tissues and that its
      gene maps to mouse chromosome 15 (human chromosome 8). This study lays the
      groundwork for future genetic approaches aimed at defining the biological role of
      this unique protein.

PMID- 12791697
TI  - RNA interference identifies two hydroperoxide metabolizing enzymes that are
      essential to the bloodstream form of the african trypanosome.
AB  - Detoxification of hydroperoxides in trypanosomes is mediated by a series of
      linked redox pathways that are dependent on the parasite-specific thiol
      trypanothione for reducing equivalents. These pathways are characterized by
      differences in subcellular location, electron transport molecules, and substrate
      specificity. To determine the functional significance of the enzymes involved, we
      have used a tetracycline-inducible RNA interference system to down-regulate
      expression of each of the corresponding transcripts in bloodstream form
      Trypanosoma brucei. We have identified two peroxidases, a cytosolic peroxiredoxin
      (TbCPX) and a member of the non-selenium glutathione-dependent peroxidase family
      (TbGPXI), that appear to be essential for the viability of this clinically
      relevant stage of the parasite life cycle. The addition of tetracycline to the
      cultures resulted in a major reduction in mRNA levels and enzyme activity, a
      dramatic fall in growth rate, and significant cell death. Furthermore, within 20
      h of adding tetracycline, cells in which the cytosolic peroxiredoxin transcript
      was targeted were found to be 16-fold more susceptible to killing by exogenous
      hydrogen peroxide. We also observed that knockdown of the tryparedoxin TbT-PNI, a
      thioredoxin-like protein that facilitates electron transport to both TbCPX and
      TbGPXI, resulted in a reduction in growth rate. These experiments therefore
      identify redox pathways that are essential for oxidative defense in T. brucei and
      validate the corresponding peroxidases as targets for drug design.

PMID- 12791696
TI  - Chronic mild hypoxia protects heart-derived H9c2 cells against acute
      hypoxia/reoxygenation by regulating expression of the SUR2A subunit of the ATP
      sensitive K+ channel.
AB  - Chronic exposure to lower oxygen tension may increase cellular resistance to
      different types of acute metabolic stress. Here, we show that 24-h-long exposure
      to slightly decreased oxygen tension (partial pressure of oxygen (PO2) of 100 mm
      Hg instead of normal 144 mm Hg) confers resistance against acute
      hypoxia/reoxygenation-induced Ca2+ loading in heart-derived H9c2 cells. The
      number of ATP-sensitive K+ (K(ATP)) channels were increased in cells exposed to
      PO2 = 100 mm Hg relative to cells exposed to PO2 = 144 mm Hg. This was due to an
      increase in transcription of SUR2A, a K(ATP) channel regulatory subunit, but not
      Kir6.2, a K(ATP) channel pore-forming subunit. PO2 = 100 mm Hg also increased the
      SUR2 gene promoter activity. Experiments with cells overexpressing wild type of
      hypoxia-inducible factor (HIF)-1alpha and dominant negative HIF-1beta suggested
      that the HIF-1-signaling pathway did not participate in observed PO2-mediated
      regulation of SUR2A expression. On the other hand, NADH inhibited the effect of
      PO2 = 100 mm Hg but not the effect of PO2 = 20 mm Hg. LY 294002 and PD 184 352
      prevented PO2-mediated regulation of K(ATP) channels, whereas rapamycin was
      without any effect. HMR 1098 inhibited the cytoprotective effect of PO2 = 100 mm
      Hg, and a decrease of PO2 from 144 to 100 mm Hg did not change the expression of
      any other gene, including those involved in stress and hypoxic response, as
      revealed by Affymetrix high density oligonucleotide arrays. We conclude that
      slight hypoxia activates HIF-1alpha-independent signaling cascade leading to an
      increase in SUR2A protein, a higher density of K(ATP) channels, and a cellular
      phenotype more resistant to acute metabolic stress.

PMID- 12791698
TI  - Peroxisome proliferator-activated receptor alpha (PPARalpha) agonist treatment
      reverses PPARalpha dysfunction and abnormalities in hepatic lipid metabolism in
      ethanol-fed mice.
AB  - Proper function of the peroxisome proliferator-activated receptor alpha
      (PPARalpha) is essential for the regulation of hepatic fatty acid metabolism.
      Fatty acid levels are increased in liver during the metabolism of ethanol and
      should activate PPARalpha. However, recent in vitro data showed that ethanol
      metabolism inhibited the function of PPARalpha. We now report that ethanol
      feeding impairs fatty acid catabolism in the liver in part via blocking PPARalpha
      mediated responses in C57BL/6J mice. Ethanol feeding decreased PPARalpha/retinoid
      X receptor alpha binding in electrophoretic mobility shift assay of liver nuclear
      extracts. mRNAs for PPAR-regulated genes were reduced (long chain and medium
      chain acyl-CoA dehydrogenases) or failed to be induced (acyl-CoA oxidase, liver
      carnitine palmitoyl-CoA transferase, very long chain acyl-CoA synthetase, very
      long chain acyl-CoA dehydrogenase) in livers of the ethanol-fed animals, and
      ethanol feeding did not increase the rate of fatty acid beta-oxidation. Wy14,643,
      a PPARalpha agonist, restored the DNA binding activity of PPARalpha/retinoid X
      receptor alpha, induced mRNA levels of PPARalpha target genes, stimulated the
      rate of fatty acid beta-oxidation, and prevented fatty liver in ethanol-fed
      animals. Impairment of PPARalpha function during ethanol consumption contributes
      to the development of alcoholic fatty liver, which can be overcome by Wy14,643.

PMID- 12791699
TI  - An overactivated ATR/CHK1 pathway is responsible for the prolonged G2
      accumulation in irradiated AT cells.
AB  - Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after
      exposure of cells to ionizing radiation (IR) is essential for maintaining genomic
      integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating
      this response in all three phases of the cell cycle. However, cells lacking
      functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by
      an ATM-independent checkpoint response. The mechanism for this ataxia
      telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report
      here that the G2 checkpoint in irradiated human AT cells derives from an
      overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the
      IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These
      results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells
      and show that activation of this G2 checkpoint contributes to the survival of AT
      cells.

PMID- 12791700
TI  - The multiple site binding of carboxypeptidase Y inhibitor (IC) to the cognate
      proteinase. Implications for the biological roles of the phosphatidylethanolamine
      binding protein.
AB  - The serine carboxypeptidase inhibitor in the cytoplasm of Saccharomyces
      cerevisiae, IC, specifically inhibits vacuolar carboxypeptidase Y (CPY) and
      belongs to a functionally unknown family of phosphatidylethanolamine-binding
      proteins (PEBPs). In the presence of 1 M guanidine hydrochloride, a CPY-IC
      complex is formed and is almost fully activated. The reactivities of
      phenylmethylsulfonyl fluoride, p-chloromercuribenzoic acid, and diisopropyl
      fluorophosphate toward the complex are considerably increased in 1 M guanidine
      hydrochloride, indicating that IC contains a binding site other than its
      inhibitory reactive site. IC is able to form the complex with diisopropyl
      fluorophosphate-modified CPY. Tryptic digestion of the complex indicates that two
      fragments from IC are involved in complex formation with CPY. These findings
      demonstrate the multiple site binding of IC with CPY. Considering the fact that
      mouse PEBP has recently been identified as a novel thrombin inhibitor, the
      binding that characterizes the CPY-IC complex could be a common feature of PEBPs.

PMID- 12791701
TI  - Induction of glia maturation factor-beta in proximal tubular cells leads to
      vulnerability to oxidative injury through the p38 pathway and changes in
      antioxidant enzyme activities.
AB  - Proteinuria is an independent risk factor for progression of renal diseases. Glia
      maturation factor-beta (GMF-beta), a 17-kDa brain-specific protein originally
      purified as a neurotrophic factor from brain, was induced in renal proximal
      tubular (PT) cells by proteinuria. To examine the role of GMF-beta in PT cells,
      we constructed PT cell lines continuously expressing GMF-beta. The PT cells
      overexpressing GMF-beta acquired susceptibility to cell death upon stimulation
      with tumor necrosis factor-alpha and angiotensin II, both of which are reported
      to cause oxidative stress. GMF-beta overexpression also promoted oxidative
      insults by H2O2, leading to the reorganization of F-actin as well as apoptosis in
      non-brain cells (not only PT cells, but also NIH 3T3 cells). The measurement of
      intracellular reactive oxygen species in the GMF-beta-overexpressing cells showed
      a sustained increase in H2O2 in response to tumor necrosis factor-alpha,
      angiotensin II, and H2O2 stimuli. The sustained increase in H2O2 was caused by an
      increase in the activity of the H2O2-producing enzyme copper/zinc-superoxide
      dismutase, a decrease in the activities of the H2O2-reducing enzymes catalase and
      glutathione peroxidase, and a depletion of the content of the cellular
      glutathione peroxidase substrate GSH. The p38 pathway was significantly involved
      in the sustained oxidative stress to the cells. Taken together, the alteration of
      the antioxidant enzyme activities, in particular the peroxide-scavenging deficit,
      underlies the susceptibility to cell death in GMF-beta-overexpressing cells. In
      conclusion, we suggest that the proteinuria induction of GMF-beta in renal PT
      cells may play a critical role in the progression of renal diseases by enhancing
      oxidative injuries.

PMID- 12791702
TI  - Subcellular localization and mechanisms of nucleocytoplasmic trafficking of
      steroid receptor coactivator-1.
AB  - Steroid hormone receptors are ligand-stimulated transcription factors that
      modulate gene transcription by recruiting coregulators to gene promoters.
      Subcellular localization and dynamic movements of transcription factors have been
      shown to be one of the major means of regulating their transcriptional activity.
      In the present report we describe the subcellular localization and the dynamics
      of intracellular trafficking of steroid receptor coactivator 1 (SRC-1). After its
      synthesis in the cytoplasm, SRC-1 is imported into the nucleus, where it
      activates transcription and is subsequently exported back to the cytoplasm. In
      both the nucleus and cytoplasm, SRC-1 is localized in speckles. The
      characterization of SRC-1 nuclear localization sequence reveals that it is a
      classic bipartite signal localized in the N-terminal region of the protein,
      between amino acids 18 and 36. This sequence is highly conserved within the other
      members of the p160 family. Additionally, SRC-1 nuclear export is inhibited by
      leptomycin B. The region involved in its nuclear export is localized between
      amino acids 990 and 1038. It is an unusually large domain differing from the
      classic leucine-rich NES sequences. Thus SRC-1 nuclear export involves either an
      alternate type of NES or is dependent on the interaction of SRC-1 with a protein,
      which is exported through the crm1/exportin pathway. Overall, the intracellular
      trafficking of SRC-1 might be a mechanism to regulate the termination of hormone
      action, the interaction with other signaling pathways in the cytoplasm and its
      degradation.

PMID- 12791703
TI  - Direct activation of AMP-activated protein kinase stimulates nitric-oxide
      synthesis in human aortic endothelial cells.
AB  - Recent studies have indicated that endothelial nitric-oxide synthase (eNOS) is
      regulated by reversible phosphorylation in intact endothelial cells. AMP
      activated protein kinase (AMPK) has previously been demonstrated to phosphorylate
      and activate eNOS at Ser-1177 in vitro, yet the function of AMPK in endothelium
      is poorly characterized. We therefore determined whether activation of AMPK with
      5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) stimulated NO production
      in human aortic endothelial cells. AICAR caused the time- and dose-dependent
      stimulation of AMPK activity, with a concomitant increase in eNOS Ser-1177
      phosphorylation and NO production. AMPK was associated with immunoprecipitates of
      eNOS, yet this was unaffected by increasing concentrations of AICAR. AICAR also
      caused the time- and dose-dependent stimulation of protein kinase B
      phosphorylation. To confirm that the effects of AICAR were indeed mediated by
      AMPK, we utilized adenovirus-mediated expression of a dominant negative AMPK
      mutant. Expression of dominant negative AMPK attenuated AICAR-stimulated AMPK
      activity, eNOS Ser-1177 phosphorylation and NO production and was without effect
      on AICAR-stimulated protein kinase B Ser-473 phosphorylation or NO production
      stimulated by insulin or A23187. These data suggest that AICAR-stimulated NO
      production is mediated by AMPK as a consequence of increased Ser-1177
      phosphorylation of eNOS. We propose that stimuli that result in the acute
      activation of AMPK activity in endothelial cells stimulate NO production, at
      least in part due to phosphorylation and activation of eNOS. Regulation of
      endothelial AMPK therefore provides an additional mechanism by which local
      vascular tone may be controlled.

PMID- 12791704
TI  - Inducible cAMP early repressor (ICER) is a negative-feedback regulator of cardiac
      hypertrophy and an important mediator of cardiac myocyte apoptosis in response to
      beta-adrenergic receptor stimulation.
AB  - Although stimulation of the beta-adrenergic receptor increases levels of cAMP and
      activation of the cAMP response element (CRE) in cardiac myocytes, the role of
      the signaling mechanism regulated by cAMP in hypertrophy and apoptosis is not
      well understood. In this study we show that protein expression of inducible cAMP
      early repressor (ICER), an endogenous inhibitor of CRE-mediated transcription, is
      induced by stimulation of isoproterenol (ISO), a beta-adrenergic agonist with a
      peak at approximately 12 hours and persisting for more than 24 hours in neonatal
      rat cardiac myocytes. ICER is also upregulated by phenylephrine but not by
      endothelin-1. Continuous infusion of ISO also increased ICER in the rat heart in
      vivo. Overexpression of ICER significantly attenuated ISO- and phenylephrine
      induced cardiac hypertrophy but did not inhibit endothelin-1-induced cardiac
      hypertrophy. Overexpression of ICER also stimulated cardiac myocyte apoptosis.
      Antisense inhibition of ICER significantly enhanced beta-adrenergic hypertrophy,
      whereas it significantly inhibited beta-adrenergic cardiac myocyte apoptosis,
      suggesting that endogenous ICER works as an important regulator of cardiac
      hypertrophy and apoptosis. Inhibition of CRE-mediated transcription by dominant
      negative CRE binding protein inhibited cardiac hypertrophy, whereas it stimulated
      cardiac myocyte apoptosis, thereby mimicking the effect of ICER. Both ISO and
      ICER reduced expression of Bcl-2, an antiapoptotic molecule, whereas antisense
      ICER prevented ISO-induced downregulation of Bcl-2. These results suggest that
      ICER is upregulated by cardiac hypertrophic stimuli increasing CRE-mediated
      transcription in cardiac myocytes and acts as a negative regulator of hypertrophy
      and a positive mediator of apoptosis, in part through both inhibition of CRE
      mediated transcription and downregulation of Bcl-2.

PMID- 12791705
TI  - Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via
      sympathetic nervous system: possible involvement in neural mechanisms of
      hypertension.
AB  - Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an
      important role in various cellular functions, including actin cytoskeleton
      organization and vascular smooth muscle contraction. This pathway is also present
      in the central nervous system and is involved in the maintenance of dendritic
      spines and axon outgrowth and in the regulation of neurotransmitter release.
      However, its role in central blood pressure regulation is unknown. In the present
      study, blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii
      (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor
      decreased blood pressure, heart rate, and renal sympathetic nerve activity in
      both Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). However,
      the magnitude of decreases in these variables was greater in SHR than in WKY
      rats. In addition, an adenovirus vector encoding dominant-negative Rho-kinase
      decreased blood pressure, heart rate, and urinary norepinephrine excretion in
      both WKY rats and SHR in an awake and free-moving state. The magnitude of
      decreases in these variables was also greater in SHR than in WKY rats.
      Furthermore, membrane RhoA expression and Rho-kinase activity in the NTS were
      enhanced in SHR compared with WKY rats. These observations indicate that the
      Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via
      the sympathetic nervous system in vivo and suggest that activation of this
      pathway is involved in the central mechanisms of hypertension.

PMID- 12791706
TI  - Ca2+ scraps: local depletions of free [Ca2+] in cardiac sarcoplasmic reticulum
      during contractions leave substantial Ca2+ reserve.
AB  - Free [Ca2+] inside the sarcoplasmic reticulum ([Ca2+]SR) is difficult to measure
      yet critically important in controlling many cellular systems. In cardiac
      myocytes, [Ca2+]SR regulates cardiac contractility. We directly measure [Ca2+]SR
      in intact cardiac myocytes dynamically and quantitatively during beats, with high
      spatial resolution. Diastolic [Ca2+]SR (1 to 1.5 mmol/L) is only partially
      depleted (24% to 63%) during contraction. There is little temporal delay in the
      decline in [Ca2+]SR at release junctions and between junctions, indicating rapid
      internal diffusion. The incomplete local Ca2+ release shows that the inherently
      positive feedback of Ca2+-induced Ca2+ release terminates, despite a large
      residual driving force. These findings place stringent novel constraints on how
      excitation-contraction coupling works in heart and also reveal a Ca2+ store
      reserve that could in principle be a therapeutic target to enhance cardiac
      function in heart failure.

PMID- 12791707
TI  - Human embryonic stem cells develop into multiple types of cardiac myocytes:
      action potential characterization.
AB  - Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid
      bodies (EBs) composed of derivatives of all three embryonic germ layers.
      Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs);
      however, the types of human CMs and their functional properties are unknown. This
      study characterizes the contractions and action potentials (APs) from beating EB
      outgrowths cultured for 40 to 95 days. Spontaneous and electrical field
      stimulated contractions were measured with video edge-detection microscopy. beta
      Adrenergic stimulation with 1.0 micromol/L isoproterenol resulted in a
      significant increase in contraction magnitude. Intracellular electrical
      recordings using sharp KCl microelectrodes in beating EB outgrowths revealed
      three distinct classes of APs: nodal-like, embryonic atrial-like, and embryonic
      ventricular-like. The APs were described as embryonic based on the relatively
      depolarized resting membrane potential and slow AP upstroke. Repeated impalements
      of an individual beating outgrowth revealed a reproducible AP morphology recorded
      from different cells, suggesting that each outgrowth is composed of a predominant
      cell type. Complex functional properties typical of cardiac muscle were observed
      in the hES cell-derived CMs including rate adaptation of AP duration and provoked
      early and delayed afterdepolarizations. Repolarization of the AP showed a
      significant role for IKr based on E-4031 induced prolongation of AP duration as
      anticipated for human CMs. In conclusion, hES cells can differentiate into
      multiple types of CMs displaying functional properties characteristic of
      embryonic human cardiac muscle. Thus, hES provide a renewable source of distinct
      types of human cardiac myocytes for basic research, pharmacological testing, and
      potentially therapeutic applications.

PMID- 12791709
TI  - Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure.
AB  - Aldosterone classically promotes unidirectional transepithelial sodium transport,
      thereby regulating blood volume and blood pressure. Recently, both clinical and
      experimental studies have suggested additional, direct roles for aldosterone in
      the cardiovascular system. To evaluate aldosterone activation of cardiomyocyte
      mineralocorticoid receptors, transgenic mice overexpressing 11beta-hydroxysteroid
      dehydrogenase type 2 in cardiomyocytes were generated using the mouse alpha
      myosin heavy chain promoter. This enzyme converts glucocorticoids to receptor
      inactive metabolites, allowing aldosterone occupancy of cardiomyocyte
      mineralocorticoid receptors. Transgenic mice were normotensive but spontaneously
      developed cardiac hypertrophy, fibrosis, and heart failure and died prematurely
      on a normal salt diet. Eplerenone, a selective aldosterone blocker, ameliorated
      this phenotype. These studies confirm the deleterious consequences of
      inappropriate activation of cardiomyocyte mineralocorticoid receptors by
      aldosterone and reveal a tonic inhibitory role of glucocorticoids in preventing
      such outcomes under physiological conditions. In addition, these data support the
      hypothesis that aldosterone blockade may provide additional therapeutic benefit
      in the treatment of heart failure.

PMID- 12791708
TI  - Homocellular conduction along endothelium and smooth muscle of arterioles in
      hamster cheek pouch: unmasking an NO wave.
AB  - We investigated roles for homocellular (endothelium or smooth muscle) and
      heterocellular (myoendothelial) conduction pathways along hamster cheek pouch
      arterioles in vivo (n=64; diameter, 33+/-1 microm). Endothelium-dependent and 
      independent vasoactive agents were delivered from micropipettes (0.5 or 1 second
      pulse) onto an arteriole while observing diameter changes at defined distances
      along the vessel. Acetylcholine (ACh) produced maximal diameter (63+/-1 microm)
      locally and vasodilation conducted rapidly ( approximately 10 microm response at
      2 mm, <1 second). Responses to bradykinin (BK) were similar, whereas sodium
      nitroprusside produced maximal dilation locally without conduction. KCl evoked
      biphasic conduction of vasoconstriction and vasodilation, whereas phenylephrine
      (PE) produced conducted vasoconstriction. Disrupting the integrity of endothelium
      as a conduction pathway using focal light-dye treatment (LDT) abolished conducted
      vasodilation to BK and to KCl but not to ACh. Disruption of smooth muscle
      integrity with LDT abolished conducted vasoconstriction with no effect on
      conducted vasodilation. After LDT of respective cell layers at sites 1 mm apart,
      vasodilation to ACh conducted past disrupted smooth muscle or disrupted
      endothelium, but not beyond both sites in series. The loss of conduction after
      selective LDT indicates a lack of effective myoendothelial coupling along the
      arteriolar wall. During NO synthase inhibition (L-NA, 100 micromol/L), conducted
      vasodilation was abolished to BK and to KCl yet remained intact to ACh. However,
      after LDT of smooth muscle, L-NA inhibited conduction to ACh by 60%. Thus,
      conduction of vasodilation entails a wave of NO release along arteriolar
      endothelium that is masked when smooth muscle provides a parallel conduction
      pathway.

PMID- 12791710
TI  - Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac
      muscles.
AB  - To investigate the regulation of the actomyosin crossbridge cycle in cardiac
      muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of
      force redevelopment (ktr) were measured. We report that CP is a primary
      determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac
      muscles, because a reduction of CP from 25 to 2.5 mmol/L decreased ktr by 51%
      despite the presence of 5 mmol/L MgATP. The effects of CP on ktr were not a
      reflection of reduced ATP or accumulated ADP, because lowering ATP to 1 mmol/L or
      increasing ADP to 1 mmol/L did not significantly decrease ktr. Therefore, the
      effect of CP on the actomyosin crossbridge cycle is proposed to occur through a
      functional link between ADP release from myosin and its rephosphorylation by CP
      creatine kinase to regenerate ATP. In activated fibers, the functional link
      influenced the kinetics of activated crossbridges without affecting the aggregate
      number of force-generating crossbridges. This was demonstrated by the ability of
      CP to affect ktr in maximally and submaximally activated fibers without altering
      the force per cross-sectional area. The data also confirm the important
      contribution of strong binding crossbridges to cardiac muscle activation, likely
      mediated by cooperative recruitment of adjacent crossbridges to maximize force
      redevelopment against external load. These data provide additional insight into
      the role of CP during pathophysiological conditions such as ischemia, suggesting
      that decreased CP may serve as a primary determinant in the observed decline of
      dP/dt.

PMID- 12791711
TI  - Preventing and treating influenza.

PMID- 12791712
TI  - Editorial misconduct.

PMID- 12791713
TI  - Impartial careers advice for doctors and medical students.

PMID- 12791714
TI  - Extending the boundaries of transplantation.

PMID- 12791716
TI  - EU agrees deal on cheaper drugs for developing world.

PMID- 12791719
TI  - Governors resist Bush plan to rein in Medicaid costs.

PMID- 12791722
TI  - Spread of SARS slows.

PMID- 12791724
TI  - Smoke free areas do not harm profits, survey shows.

PMID- 12791726
TI  - Canadian government is attacked for plan to legalise marijuana.

PMID- 12791727
TI  - Court rules food and hydration are treatment.

PMID- 12791728
TI  - Bush legislates for $15bn to be spent on AIDS.

PMID- 12791729
TI  - Waiting times for breast cancer test results have risen in past two years.

PMID- 12791730
TI  - Schering-Plough is accused of overcharging and of obstructing justice.

PMID- 12791732
TI  - India agrees to help Nigeria tackle the import of fake drugs.

PMID- 12791733
TI  - Mental health diseases are an economic burden on patients, says report.

PMID- 12791734
TI  - Ministry of Defence accused of contravening inoculation guidelines.

PMID- 12791735
TI  - Effectiveness of neuraminidase inhibitors in treatment and prevention of
      influenza A and B: systematic review and meta-analyses of randomised controlled
      trials.
AB  - OBJECTIVE: To review the clinical effectiveness of oseltamivir and zanamivir for
      the treatment and prevention of influenza A and B. DESIGN: Systematic review and
      meta-analyses of randomised controlled trials. DATA SOURCES: Published studies
      were retrieved from electronic bibliographic databases; supplementary data were
      obtained from the manufacturers. SELECTION OF STUDIES: Randomised controlled,
      double blind trials that were published in English, had data available before 31
      December 2001, evaluated treatment or prevention of naturally occurring influenza
      with zanamivir or oseltamivir (if given using the formulation and dosage licensed
      for clinical use), and reported at least one end point of relevance. REVIEW
      METHODS: The main outcome measures were the median time to the alleviation of
      symptoms (for treatment trials) and number of flu episodes avoided (for
      prevention trials). Three population groups were defined: children aged 12 years
      and under; otherwise healthy individuals aged 12 to 65 years; and "high risk"
      individuals (those with certain chronic medical conditions or aged 65 years and
      older). RESULTS: Seventeen treatment trials and seven prevention trials
      identified met the inclusion criteria. All trials included compared one of the
      drugs against placebo or standard care. Treatment of children, otherwise healthy
      individuals, and high risk populations with zanamivir reduced the median duration
      of symptoms in days respectively by 1.0 (95% confidence interval 0.5 to 1.5), 0.8
      (0.3 to 1.3), and 0.9 (-0.1 to 1.9) for the intention to treat population. The
      corresponding results, in days, for oseltamivir were 0.9 (0.3 to 1.5), 0.9 (0.3
      to 1.4), and 0.4 (-0.7 to 1.4). The effect of giving zanamivir and oseltamivir
      prophylactically resulted in a relative reduction of 70-90% in the odds of
      developing flu, depending on the strategy adopted and the population studied.
      CONCLUSIONS: Evidence from randomised controlled trials consistently supports the
      view that both oseltamivir and zanamivir are clinically effective for treating
      and preventing flu. However, evidence is limited for the treatment of certain
      populations and for all prevention strategies.

PMID- 12791736
TI  - We need to determine who benefits most from flu treatments.

PMID- 12791737
TI  - Social factors and increase in mortality in Russia in the 1990s: prospective
      cohort study.
AB  - OBJECTIVE: To determine the association between social factors and the increase
      in mortality in Russia in the 1990s. DESIGN: Prospective population cohort study.
      SETTING: Saint Petersburg, Russia. PARTICIPANTS: Two cohorts of men aged 40-59
      years randomly selected from district voting list: 3907 screened in 1975-7 and
      1467 in 1986-8. MAIN OUTCOME MEASURES: Education, various health related
      measures, alcohol intake. Mortality in subsequent 10 years. RESULTS: There was no
      recorded increase in mortality in men with university degrees. The relative risk
      in the second cohort compared with the first was 0.92 (95% confidence interval
      0.67 to 1.24). For participants with only high school education it was
      significantly higher in the second cohort (1.32, 1.02 to 1.71). The most
      pronounced differences were found among participants with the lowest level of
      education, in which the relative risk was 1.75 (1.44 to 2.12). The same pattern
      held for coronary vascular disease and cancer mortality. CONCLUSION: In Russia
      men in the lower socioeconomic groups were most affected by the sharp increases
      in mortality in the 1990s.

PMID- 12791738
TI  - Instrument for objective assessment of appropriateness of surgical bed occupancy:
      validation study.

PMID- 12791739
TI  - Representation of South Asian people in randomised clinical trials: analysis of
      trials' data.

PMID- 12791740
TI  - Average energy intake among pregnant women carrying a boy compared with a girl.

PMID- 12791741
TI  - Meta-analysis of data on costs from trials of counselling in primary care: using
      individual patient data to overcome sample size limitations in economic analyses.
AB  - OBJECTIVE: To assess the feasibility of overcoming sample size limitations in
      economic analyses of clinical trials through meta-analysis of data on individual
      patients from multiple trials. DESIGN: Meta-analysis of individual patient data
      from trials of counselling in primary care compared with usual care by a general
      practitioner. SETTING: Primary care. PATIENTS: People with mental health
      problems. MAIN OUTCOME MEASURES: Direct treatment costs, depressive symptoms, and
      cost effectiveness. RESULTS: Meta-analysis of individual patient data proved
      feasible. The results showed that the previous analyses of individual trials were
      underpowered to provide useful conclusions about the cost comparisons. The
      results are sensitive to assumptions made about the costs of sessions with a
      counsellor and the management of patients by a general practitioner. CONCLUSIONS:
      Meta-analysis of individual patient data may assist in overcoming sample size
      limitations in economic analyses. Although feasible, such analysis has
      shortcomings that may limit the validity of the results. The relative costs and
      benefits of this method, as opposed to further collection of primary data, are as
      yet unclear.

PMID- 12791742
TI  - Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal
      osteoporosis: comparative study in primary care.

PMID- 12791743
TI  - Opportunistic screening for Chlamydia at a community based contraceptive service
      for young people.
AB  - PROBLEM: The suspected high prevalence of Chlamydia infection that is undiagnosed
      and untreated among high risk women who attend a contraceptive service for young
      people. DESIGN: Cross sectional study from a community screening service.
      BACKGROUND AND SETTING: An inner city contraceptive and psychotherapy service for
      young people aged 12-21 years. KEY MEASURE FOR IMPROVEMENT: Prevalence of
      infection commensurate with or above findings from the national screening pilot
      (13.8% for > 16 year olds, 10.5% for 16-19 year olds, and 7.2% for 20 to 24 year
      olds). STRATEGIES FOR CHANGE: Offering testing (of a first catch urine sample)
      for Chlamydia to all young people using the contraceptive service who were not
      previously screened; launching a publicity campaign about the new service;
      training medical staff and reception staff to deliver the service to maximise
      take up of screening and of treatment by infected cases; and surveying results
      from testing to monitor significant patterns of infection requiring further
      action. EFFECTS OF CHANGE: Percentage of clients with infection exceeded targets
      for each age group, 76% with a positive or equivocal result returned for
      treatment, 87% of those treated returned for a test of cure, and 99% of tests of
      cure were negative. Prevention work was initiated in a school with a particularly
      heavy concentration of infected clients. LESSONS LEARNT: A contraceptive service
      for young women is a highly acceptable location for effective Chlamydia
      screening.

PMID- 12791744
TI  - Treating head lice.

PMID- 12791745
TI  - How to advise a patient when over the counter products have failed.

PMID- 12791746
TI  - A parent's story: "I felt lost and hysterical".

PMID- 12791747
TI  - Information for patients: removal of lice and eggs by combing.

PMID- 12791748
TI  - Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial
      infarction.

PMID- 12791749
TI  - Pitfalls of editorial miscommunication.

PMID- 12791750
TI  - Mortality associated with foodborne bacterial gastrointestinal infections: case
      selection and clinical data are important.

PMID- 12791751
TI  - Mortality associated with foodborne bacterial gastrointestinal infections:
      mechanism needs to be explained.

PMID- 12791752
TI  - Mortality associated with foodborne bacterial gastrointestinal infections:
      statistical method is worth examining.

PMID- 12791753
TI  - Mortality in Swedish women with cosmetic breast implants: study found increased
      risk of suicides and cancer deaths.

PMID- 12791754
TI  - Mortality in Swedish women with cosmetic breast implants: body dysmorphic
      disorder should be considered.

PMID- 12791755
TI  - "Evidence of absence" can be important.

PMID- 12791756
TI  - Routine telephone review of asthma: measurement of quality dimensions causes
      concern.

PMID- 12791757
TI  - Routine telephone review of asthma: further investigation is required.

PMID- 12791758
TI  - Consumption of coffee during pregnancy: authors should adjust for history of drug
      abuse.

PMID- 12791759
TI  - Consumption of coffee during pregnancy: data do not support claim.

PMID- 12791760
TI  - Consumption of coffee during pregnancy: article raises more questions than it
      answers.

PMID- 12791761
TI  - Doctors as servants of patients: long term patients are underused resource.

PMID- 12791762
TI  - Doctors as servants of patients: surely we can do better than this.

PMID- 12791763
TI  - Doctors as servants of patients: modesty may be deceptive.

PMID- 12791764
TI  - Unfinished business and modernising medical careers.

PMID- 12791765
TI  - Informing choices: the inside story.

PMID- 12791766
TI  - Senior house officer foundation programmes in action.

PMID- 12791767
TI  - Changing the culture to support doctors' careers.

PMID- 12791768
TI  - The implications of Modernising Medical Careers for specialist registrars.

PMID- 12791769
TI  - Activation domains of CCAAT enhancer binding protein delta: regions required for
      native activity and prostaglandin E2-dependent transactivation of insulin-like
      growth factor I gene expression in rat osteoblasts.
AB  - In osteoblasts, hormones such as prostaglandin E2 that activate protein kinase A
      increase the translocation of transcription factor CCAAT/enhancer binding protein
      delta (C/EBPdelta) from the cytoplasm to the nucleus where it rapidly induces IGF
      I gene expression. In this study, we identified activation and suppression
      domains in C/EBPdelta using native and heterologous gene promoter assay systems.
      We demonstrated functional interactions between C/EBPdelta and trans-gene
      expressed cAMP response element binding protein-binding protein, and showed that
      the ability of C/EBPdelta to promote gene expression was suppressed by viral
      protein E1A, which blocks the activity of native cAMP response element binding
      protein-binding protein. Site-directed mutations at serines 62 or 191 within
      C/EBPdelta reduced its basal transcriptional activity, whereas mutation at serine
      191 suppressed the stimulatory effect of prostaglandin E2 on C/EBPdelta function
      as well as its DNA binding potential. These results are consistent with the
      location of serine 191 in the DNA binding domain of C/EBPdelta. Our studies
      provide the first evidence for regions of C/EBPdelta that are important for basal
      and for hormone-induced transcriptional activity, and for its interactions with
      other enhancers and suppressers of gene expression.

PMID- 12791770
TI  - Differential modulation of androgen receptor action by deoxyribonucleic acid
      response elements.
AB  - In addition to the steroid response elements (SREs), which are recognized by
      several steroid receptors, a second class of DNA elements exhibiting selectivity
      for the androgen receptor (AR) and named androgen response elements (AREs) has
      been identified. Here we provide evidence for the differential role of these
      element classes in modulating AR function. AR complexes attached to response
      elements representative of each class were purified. Limited protease digests of
      ARE- or SRE-bound AR complexes led to the generation of different patterns, in
      line with differential accessibilities. In transactivation assays, mutations in
      the AR dimerization interface of the DNA-binding domain had various effects,
      depending on the response elements tested. The R598D mutant displayed much
      enhanced activity on SREs, whereas far less effect was seen on the selective
      AREs. The A596T mutant had reduced activity on AREs but not on SREs. Ectopic
      expression of the coactivators transcriptional intermediary factor 2 (TIF2) and
      ARA55 stimulated AR activity to different extents, depending on the response
      element. When using cysteine-rich secretory protein 1 (CRISP-1) SRE as reference,
      the most significant difference was observed with Pem ARE-2. A differential
      response of each element class was furthermore observed in the presence of two
      enzymes involved in the sumoylation pathway. Ubiquitin-conjugating enzyme 9
      (Ubc9) overexpression enhanced AR action conveyed by SREs, whereas little effect
      was seen on Pem ARE-1 and repression on Pem ARE-2. Protein inhibitor of activated
      STAT (PIAS)xalpha overexpression had little influence on SRE-mediated AR activity
      but was repressive when using AREs. Altogether, these results demonstrate that
      DNA response elements play an important modulatory role in transmitting AR action
      and may be determinative for specificity of gene expression in cell or tissue
      types.

PMID- 12791771
TI  - The antiangiogenic factor 16K human prolactin induces caspase-dependent apoptosis
      by a mechanism that requires activation of nuclear factor-kappaB.
AB  - We have previously shown that the 16-kDa N-terminal fragment of human prolactin
      (16K hPRL) has antiangiogenic properties, including the ability to induce
      apoptosis in vascular endothelial cells. Here, we examined whether the nuclear
      factor-kappaB (NF-kappaB) signaling pathway was involved in mediating the
      apoptotic action of 16K hPRL in bovine adrenal cortex capillary endothelial
      cells. In a dose-dependent manner, treatment with 16K hPRL induced inhibitor
      kappaB-alpha degradation permitting translocation of NF-kappaB to the nucleus and
      reporter gene activation. Inhibition of NF-kappaB activation by overexpression of
      a nondegradable inhibitor kappaB-alpha mutant or treatment with NF-kappaB
      inhibitors blocked 16K hPRL-induced apoptosis. Treatment with 16K hPRL activated
      the initiator caspases-8 and -9 and the effector caspase-3, all of which were
      essential for stimulation of DNA fragmentation. This activation of the caspase
      cascade by 16K hPRL was also NF-kappaB dependent. These findings support the
      conclusion that NF-kappaB signaling plays a central role in 16K hPRL-induced
      apoptosis in vascular endothelial cells.

PMID- 12791772
TI  - Tyrosine phosphorylation of the beta3-subunit of the alphaVbeta3 integrin is
      required for embrane association of the tyrosine phosphatase SHP-2 and its
      further recruitment to the insulin-like growth factor I receptor.
AB  - Ligand occupancy of the alphaVbeta3 integrin is required for IGF-I receptor (IGF
      IR) phosphorylation of an appropriate duration and for stimulation of IGF-I
      actions. In vascular smooth muscle cells (SMCs), the tyrosine phosphatase SHP-2
      regulates the duration of IGF-IR phosphorylation and biological actions. We
      determined the role of ligand occupancy of the alphaVbeta3 integrin on beta3
      phosphorylation and studied the role of beta3 phosphorylation in regulating both
      SHP-2 recruitment to the cell membrane and IGF-I-dependent biological responses.
      Vitronectin binding to alphaVbeta3 induced tyrosine phosphorylation of the beta3
      subunit in subconfluent SMCs and was accompanied by increased association of SHP
      2 with beta3. In confluent SMCs, the beta3-subunit was constitutively
      phosphorylated leading to basal binding of SHP-2. The Src kinase inhibitor PP2
      caused a concentration-dependent decrease in beta3 phosphorylation and resulted
      in decreased SHP-2 association with beta3 and with the cell membrane. In contrast
      to control cells, SMCs expressing a mutant beta3 that had two tyrosines changed
      to phenylalanines showed a 89.9 +/- 1.2% decrease in beta3 phosphorylation. This
      decrease was associated with reduced SHP-2 binding to nonphosphorylated beta3 and
      a corresponding decrease in the membrane association of SHP-2. When IGF-I was
      added to cells expressing mutant beta3, SHP-2 was not recruited to the Src
      homology 2 domain-containing tyrosine phosphatase substrate-1 or to IGF-IR. This
      was associated with prolonged IGF-IR phosphorylation and an impaired cellular DNA
      synthesis response to IGF-I. These results define a mechanism by which ligand
      occupancy of alphaVbeta3 regulates the SMC response to IGF-I.

PMID- 12791773
TI  - Draft framework for evaluating syndromic surveillance systems.
AB  - Interest in public health surveillance to detect outbreaks from terrorism is
      driving the exploration of nontraditional data sources and development of new
      performance priorities for surveillance systems. A draft framework for evaluating
      syndromic surveillance systems will help researchers and public health
      practitioners working on nontraditional surveillance to review their work in a
      systematic way and communicate their efforts. The framework will also guide
      public health practitioners in their efforts to compare and contrast aspects of
      syndromic surveillance systems and decide whether and how to develop and maintain
      such systems. In addition, a common framework will allow the identification and
      prioritization of research and evaluation needs. The evaluation framework is
      comprised of five components: a thorough description of the system (e.g.,
      purpose, stakeholders, how the system works); system performance experience
      (e.g., usefulness, acceptability to stakeholders, generalizability to other
      settings, operating stability, costs); capacity for outbreak detection (e.g.,
      flexibility to adapt to changing risks and data inputs, sensitivity to detect
      outbreaks, predictive value of system alarms for true outbreaks, timeliness of
      detection); assessment of data quality (e.g., representativeness of the
      population covered by the system, completeness of data capture, reliability of
      data captured over time); and conclusions and recommendations. The draft
      framework is intended to evolve into guidance to support public health practice
      for terrorism preparedness and outbreak detection.

PMID- 12791774
TI  - Statutory basis for public health reporting beyond specific diseases.
AB  - Statutory authority for public health surveillance is necessarily broad as
      previously uncharacterized diseases are regularly discovered. This article
      provides specific information about general disease reporting provisions in each
      state. The intent of these reporting laws and the Health Insurance Portability
      and Accountability Act Privacy Rule is to support this critical disease
      surveillance function for the benefit of the entire population.

PMID- 12791775
TI  - New York City and state legal authorities related to syndromic surveillance.

PMID- 12791776
TI  - Syndromic surveillance using minimum transfer of identifiable data: the example
      of the National Bioterrorism Syndromic Surveillance Demonstration Program.
AB  - Several health plans and other organizations are collaborating with the Centers
      for Disease Control and Prevention to develop a syndromic surveillance system
      with national coverage that includes more than 20 million people. A principal
      design feature of this system is reliance on daily reporting of counts of
      individuals with syndromes of interest in specified geographic regions rather
      than reporting of individual encounter-level information. On request from public
      health agencies, health plans and telephone triage services provide additional
      information regarding individuals who are part of apparent clusters of illness.
      This reporting framework has several advantages, including less sharing of
      protected health information, less risk that confidential information will be
      distributed inappropriately, the prospect of better public acceptance, greater
      acceptance by health plans, and less effort and cost for both health plans and
      public health agencies. If successful, this system will allow any organization
      with appropriate data to contribute vital information to public health syndromic
      surveillance systems while preserving individuals' privacy to the greatest extent
      possible.

PMID- 12791777
TI  - A systems overview of the Electronic Surveillance System for the Early
      Notification of Community-Based Epidemics (ESSENCE II).
AB  - The Electronic Surveillance System for the Early Notification of Community-Based
      Epidemics, or ESSENCE II, uses syndromic and nontraditional health information to
      provide very early warning of abnormal health conditions in the National Capital
      Area (NCA). ESSENCE II is being developed for the Department of Defense Global
      Emerging Infections System and is the only known system to combine both military
      and civilian health care information for daily outbreak surveillance. The
      National Capital Area has a complicated, multijurisdictional structure that makes
      data sharing and integrated regional surveillance challenging. However, the
      strong military presence in all jurisdictions facilitates the collection of
      health care information across the region. ESSENCE II integrates clinical and
      nonclinical human behavior indicators as a means of identifying the abnormality
      as close to the time of onset of symptoms as possible. Clinical data sets include
      emergency room syndromes, private practice billing codes grouped into syndromes,
      and veterinary syndromes. Nonclinical data include absenteeism, nurse hotline
      calls, prescription medications, and over-the-counter self-medications. Correctly
      using information marked by varying degrees of uncertainty is one of the more
      challenging aspects of this program. The data (without personal identifiers) are
      captured in an electronic format, encrypted, archived, and processed at a secure
      facility. Aggregated information is then provided to users on secure Web sites.
      When completed, the system will provide automated capture, archiving, processing,
      and notification of abnormalities to epidemiologists and analysts. Outbreak
      detection methods currently include temporal and spatial variations of odds
      ratios, autoregressive modeling, cumulative summation, matched filter, and scan
      statistics. Integration of nonuniform data is needed to increase sensitivity and
      thus enable the earliest notification possible. The performance of various
      detection techniques was compared using results obtained from the ESSENCE II
      system.

PMID- 12791778
TI  - Use of ambulance dispatch data as an early warning system for communitywide
      influenzalike illness, New York City.
AB  - In 1998, the New York City Department of Health and the Mayor's Office of
      Emergency Management began monitoring the volume of ambulance dispatch calls as a
      surveillance tool for biologic terrorism. We adapted statistical techniques
      designed to measure excess influenza mortality and applied them to outbreak
      detection using ambulance dispatch data. Since 1999, we have been performing
      serial daily regressions to determine the alarm threshold for the current day. In
      this article, we evaluate this approach by simulating a series of 2,200 daily
      regressions. In the influenza detection implementation of this model, there were
      71 (3.2%) alarms at the 99% level. Of these alarms, 64 (90%) occurred shortly
      before or during a period of peak influenza in each of six influenza seasons. In
      the bioterrorism detection implementation of this methodology, after accounting
      for current influenza activity, there were 24 (1.1%) alarms at the 99% level. Two
      occurred during a large snowstorm, 1 is unexplained, and 21 occurred shortly
      before or during a period of peak influenza activity in each of six influenza
      seasons. Our findings suggest that this surveillance system is sensitive to
      communitywide respiratory outbreaks with relatively few false alarms. More work
      needs to be done to evaluate the sensitivity of this approach for detecting
      nonrespiratory illness and more localized outbreaks.

PMID- 12791779
TI  - Clinical evaluation of the Emergency Medical Services (EMS) ambulance dispatch
      based syndromic surveillance system, New York City.
AB  - Since 1998, the New York City Department of Health has used New York City
      Emergency Medical Services (EMS) ambulance dispatch data to monitor for a
      communitywide rise in influenzalike illness (ILI) as an early detection system
      for bioterrorism. A clinical validation study was conducted during peak influenza
      season at six New York City emergency departments (EDs) to compare patients with
      ILI brought in by ambulance with other patients to examine potential biases
      associated with ambulance dispatch-based surveillance. We also examined the
      utility of 4 EMS call types (selected from 52) for case detection of ILI.
      Clinical ILI was defined as fever (temperature higher than 100 degrees F) on
      history or exam, along with either cough or sore throat. Of the 2,294 ED visits
      reviewed, 522 patients (23%) met the case definition for ILI, 64 (12%) of whom
      arrived by ambulance. Patients with ILI brought in by ambulance were older,
      complained of more severe symptoms, and were more likely to undergo diagnostic
      testing, be diagnosed with pneumonia, and be admitted to the hospital than
      patients who arrived by other means. The median duration of symptoms prior to
      presenting to the ED, however, was the same for both groups (48 hours). The
      selected call types had a sensitivity of 58% for clinical ILI, and a predictive
      value positive of 22%. Individuals with symptoms consistent with the prodrome of
      inhalational anthrax were likely to utilize the EMS system and usually did so
      early in the course of illness. While EMS-based surveillance is more sensitive
      for severe illness and for illness affecting older individuals, there is not
      necessarily a loss of timeliness associated with EMS-based (versus ED-based)
      surveillance.

PMID- 12791780
TI  - Biosurveillance applying scan statistics with multiple, disparate data sources.
AB  - Researchers working on the Department of Defense Global Emerging Infections
      System (DoD-GEIS) pilot system, the Electronic Surveillance System for the Early
      Notification of Community-Based Epidemics (ESSENCE), have applied scan statistics
      for early outbreak detection using both traditional and nontraditional data
      sources. These sources include medical data indexed by International
      Classification of Disease, 9th Revision (ICD-9) diagnosis codes, as well as less
      specific, but potentially timelier, indicators such as records of over-the
      counter remedy sales and of school absenteeism. Early efforts employed the
      Kulldorff scan statistic as implemented in the SaTScan software of the National
      Cancer Institute. A key obstacle to this application is that the input data
      streams are typically based on time-varying factors, such as consumer behavior,
      rather than simply on the populations of the component subregions. We have used
      both modeling and recent historical data distributions to obtain background
      spatial distributions. Data analyses have provided guidance on how to condition
      and model input data to avoid excessive clustering. We have used this methodology
      in combining data sources for both retrospective studies of known outbreaks and
      surveillance of high-profile events of concern to local public health
      authorities. We have integrated the scan statistic capability into a Microsoft
      Access-based system in which we may include or exclude data sources, vary time
      windows separately for different data sources, censor data from subsets of
      individual providers or subregions, adjust the background computation method, and
      run retrospective or simulated studies.

PMID- 12791781
TI  - WSARE: What's Strange About Recent Events?
AB  - This article presents an algorithm for performing early detection of disease
      outbreaks by searching a database of emergency department cases for anomalous
      patterns. Traditional techniques for anomaly detection are unsatisfactory for
      this problem because they identify individual data points that are rare due to
      particular combinations of features. Thus, these traditional algorithms discover
      isolated outliers of particularly strange events, such as someone accidentally
      shooting their ear, that are not indicative of a new outbreak. Instead, we would
      like to detect groups with specific characteristics that have a recent pattern of
      illness that is anomalous relative to historical patterns. We propose using an
      anomaly detection algorithm that would characterize each anomalous pattern with a
      rule. The significance of each rule would be carefully evaluated using the Fisher
      exact test and a randomization test. In this study, we compared our algorithm
      with a standard detection algorithm by measuring the number of false positives
      and the timeliness of detection. Simulated data, produced by a simulator that
      creates the effects of an epidemic on a city, were used for evaluation. The
      results indicate that our algorithm has significantly better detection times for
      common significance thresholds while having a slightly higher false positive
      rate.

PMID- 12791782
TI  - Enhanced drop-in syndromic surveillance in New York City following September 11,
      2001.
AB  - After the 2001 World Trade Center disaster, the New York City Department of
      Health was under heightened alert for bioterrorist attacks in the city. An
      emergency department (ED) syndromic surveillance system was implemented with the
      assistance of the Centers for Disease Control and Prevention to ensure early
      recognition of an increase or clustering of disease syndromes that might
      represent a disease outbreak, whether natural or intentional. The surveillance
      system was based on data collected 7 days a week at area EDs. Data collected were
      translated into syndromes, entered into an electronic database, and analyzed for
      aberrations in space and time within 24 hours. From September 14-27, personnel
      were stationed at 15 EDs on a 24-hour basis (first staffing period); from
      September 29-October 12, due to resource limitations, personnel were stationed at
      12 EDs on an 18-hour basis (second staffing period). A standardized form was used
      to obtain demographic information and classify each patient visit into 12
      syndrome categories. Seven of these represented early manifestations of
      bioterrorist agents. Data transfer and analysis for time and space clustering
      (alarms) by syndrome and age occurred daily. Retrospective analyses examined
      syndrome trends, differences in reporting between staffing periods, and the
      staff's experience during the project. A total of 67,536 reports were received.
      The system captured 83.9% of patient visits during the first staffing period, and
      60.8% during the second staffing period (P < 0.01). Five syndromes each accounted
      for more than 1% of visits: trauma, asthma, gastrointestinal illness, upper/lower
      respiratory infection with fever, and anxiety. Citywide temporal alarms occurred
      eight times for three of the major bioterrorism-related syndromes. Spatial
      clustering alarms occurred 16 times by hospital location and 9 times by ZIP code
      for the same three syndromes. No outbreaks were detected. On-site staffing to
      facilitate data collection and entry, supported by daily analysis of ED visits,
      is a feasible short-term approach to syndromic surveillance during high-profile
      events. The resources required to operate such a system, however, cannot be
      sustained for the long term. This system was changed to an electronic-based ED
      syndromic system using triage log data that remains in operation.

PMID- 12791783
TI  - The bioterrorism preparedness and response Early Aberration Reporting System
      (EARS).
AB  - Data from public health surveillance systems can provide meaningful measures of
      population risks for disease, disability, and death. Analysis and evaluation of
      these surveillance data help public health practitioners react to important
      health events in a timely manner both locally and nationally. Aberration
      detection methods allow the rapid assessment of changes in frequencies and rates
      of different health outcomes and the characterization of unusual trends or
      clusters. The Early Aberration Reporting System (EARS) of the Centers for Disease
      Control and Prevention allows the analysis of public health surveillance data
      using available aberration detection methods. The primary purpose of EARS is to
      provide national, state, and local health departments with several alternative
      aberration detection methods. EARS helps assist local and state health officials
      to focus limited resources on appropriate activities during epidemiological
      investigations of important public health events. Finally, EARS allows end users
      to select validated aberration detection methods and modify sensitivity and
      specificity thresholds to values considered to be of public health importance by
      local and state health departments.

PMID- 12791784
TI  - Syndromic surveillance using automated collection of computerized discharge
      diagnoses.
AB  - The Syndromic Surveillance Information Collection (SSIC) system aims to
      facilitate early detection of bioterrorism attacks (with such agents as anthrax,
      brucellosis, plague, Q fever, tularemia, smallpox, viral encephalitides,
      hemorrhagic fever, botulism toxins, staphylococcal enterotoxin B, etc.) and early
      detection of naturally occurring disease outbreaks, including large foodborne
      disease outbreaks, emerging infections, and pandemic influenza. This is
      accomplished using automated data collection of visit-level discharge diagnoses
      from heterogeneous clinical information systems, integrating those data into a
      common XML (Extensible Markup Language) form, and monitoring the results to
      detect unusual patterns of illness in the population. The system, operational
      since January 2001, collects, integrates, and displays data from three emergency
      department and urgent care (ED/UC) departments and nine primary care clinics by
      automatically mining data from the information systems of those facilities. With
      continued development, this system will constitute the foundation of a population
      based surveillance system that will facilitate targeted investigation of clinical
      syndromes under surveillance and allow early detection of unusual clusters of
      illness compatible with bioterrorism or disease outbreaks.

PMID- 12791785
TI  - Investigation of disease outbreaks detected by "syndromic" surveillance systems.
AB  - Syndromic surveillance systems can detect potential disease outbreaks quickly and
      can provide useful tools to assist in outbreak investigation. The steps used to
      investigate diseases detected through these newer methods are not that different
      from traditional investigative measures, but the differences and limitations of
      the systems must be understood. With syndromic surveillance systems, there is
      often readily available electronic demographic information that can help define
      the epidemic and direct disease control measures. The diagnosis needs to be
      confirmed as quickly as possible, however, as specific diagnostic information
      will be missing with early detection from nonspecific data. It is also important
      not to disregard smaller, nonsevere rises in disease incidence as they might be a
      harbinger of a worsening outbreak. The rapidity of most syndromic surveillance
      systems also requires an equally rapid response, and planning must be done to
      prioritize alert categories and the response sequence to best utilize the
      information available in these new systems.

PMID- 12791786
TI  - Epidemiological response to syndromic surveillance signals.

PMID- 12791792
TI  - Hard drugs and "British" solutions.

PMID- 12791794
TI  - Drug overdose: new insights, innovative surveillance, and promising
      interventions.

PMID- 12791795
TI  - Heroin overdose: research and evidence-based intervention.
AB  - Drug overdose is a major cause of premature death and morbidity among heroin
      users. This article examines recent research into heroin overdose to inform
      interventions that will reduce the rate of overdose death. The demographic
      characteristics of overdose cases are discussed, including factors associated
      with overdose: polydrug use, drug purity, drug tolerance, routes of
      administration, and suicide. Responses by heroin users at overdoses are also
      examined. Potential interventions to reduce the rate of overdose and overdose
      related morbidity are examined in light of the emerging data in this field.

PMID- 12791796
TI  - Racial/ethnic disparities in overdose mortality trends in New York City, 1990
      1998.
AB  - Racial/ethnic disparities in health and disease have been present in the United
      States for the past century. Although differences such as individual access to
      health care and health-related behaviors account for some of these health
      disparities, it is likely that a combination of individual and contextual-level
      factors determine the differential rates of disease between racial/ethnic groups.
      We studied fatal accidental drug overdose in New York City between 1990 and 1998
      to describe differences in racial/ethnic patterns over time and to develop
      hypotheses about factors that might contribute to these differences. During this
      period, rates of overdose death were consistently higher among blacks and Latinos
      compared to whites. In addition, cocaine was more common among black decedents,
      while opiates and alcohol were more common among Latino and white decedents.
      Differences in situational factors, such as differential likelihood of activating
      emergency medical response, may in part explain the consistently higher overdose
      mortality rates observed among minorities. Further study to determine the
      individual and contextual factors that explain these observed disparities in
      overdose death may identify effective areas for public health intervention and
      provide insight into factors underlying racial/ethnic disparities in other health
      outcomes.

PMID- 12791797
TI  - Prevalence and circumstances of opiate overdose among injection drug users in the
      Russian Federation.
AB  - Using a self-administered questionnaire, we examined the characteristics of
      opiate overdose in 16 cities of the Russian Federation. As indicated by responses
      from 763 injection drug users who took part in this study, 59% experienced an
      overdose, 81% reported seeing others experiencing an overdose, and 15% stated
      that they had witnessed a fatal overdose. The most common drug that caused opiate
      overdose was heroin (74%), although we also found that, in smaller towns, home
      produced opiates tended to be a major overdose-causing agent. There were a number
      of factors that increased the likelihood of overdose, such as mixing opiates with
      alcohol and tranquilizers or having a longer history of opiate use. We also found
      that injecting drug users were reluctant to seek medical assistance when their
      peers experienced an overdose because of the perceived ineffectiveness of
      ambulance services and fear of police prosecution. At the same time, 57% of
      respondents admitted that they lacked appropriate skills to treat overdose. We
      discuss the implications of these findings for overdose prevention programs in
      Russia.

PMID- 12791798
TI  - The relationship between depressive symptoms and nonfatal overdose among a sample
      of drug users in Baltimore, Maryland.
AB  - Nonfatal drug overdoses are common among heroin users. While several factors that
      increase risk of overdose have been identified, there is little research on the
      role of mental health status. The purpose of this study was to examine the
      association between depressive symptoms and history of overdose. A sample of 729
      opiate and cocaine users completed a cross-sectional survey. Of the sample, 65%
      reported never having overdosed, 31% had overdosed longer than 12 months before
      the interview, and 4% had overdosed within the past 12 months. Results indicate
      that a high score on the Center for Epidemiological Studies Depression Scale (CES
      D), a measure of depressive symptoms, was associated with having overdosed within
      the past 12 months (relative risk ratio [RRR] = 3.06; 95% confidence interval
      [CI], 1.33 to 7.05) after adjusting for age, gender, injection frequency, and
      physical health impairment. These results suggest that drug users with depressive
      symptoms should be targeted for overdose prevention programs.

PMID- 12791799
TI  - Intentional overdose among heroin overdose survivors.
AB  - Previous studies have reported varying rates of intentional overdose among heroin
      overdose survivors. This article reports on the prevalence of intentional heroin
      overdose among a sample of overdose survivors in Melbourne, Australia. This is
      part of a larger study examining the risk factors associated with nonfatal
      overdose. The study involved interviews with 256 heroin overdose survivors
      successfully resuscitated by Melbourne Ambulance Service paramedics. A
      substantial minority (17%) of the sample indicated that they had ever had an
      intentional overdose, and 67% had one within the last 6 months (11% of the total
      sample). Of those who had ever intentionally overdosed, 21% did so at the
      overdose for which they were recruited into the study (4% of total sample). Self
      reported reasons for intentional heroin overdose fell into two categories:
      precipitating events and emotional states prior to use. Intentional overdose
      appears to comprise a relatively low proportion of overall heroin overdoses.
      However, given the complexity of suicidal thought and behavior, it is possible
      that some heroin overdose survivors who report their overdose to be unintentional
      were in fact experiencing some degree of suicidal thinking at the time of the
      overdose. Future research could address the potentially ambiguous nature of some
      intentional heroin overdoses.

PMID- 12791800
TI  - Nonfatal heroin overdoses in Queensland, Australia: an analysis of ambulance
      data.
AB  - In the past decade, the utilization of ambulance data to inform the prevalence of
      nonfatal heroin overdose has increased. These data can assist public health
      policymakers, law enforcement agencies, and health providers in planning and
      allocating resources. This study examined the 672 ambulance attendances at
      nonfatal heroin overdoses in Queensland, Australia, in 2000. Gender distribution
      showed a typical 70/30 male-to-female ratio. An equal number of persons with
      nonfatal heroin overdose were between 15 and 24 years of age and 25 and 34 years
      of age. Police were present in only 1 of 6 cases, and 28.1% of patients reported
      using drugs alone. Ambulance data are proving to be a valuable population-based
      resource for describing the incidence and characteristics of nonfatal heroin
      overdose episodes. Future studies could focus on the differences between nonfatal
      heroin overdose and fatal heroin overdose samples.

PMID- 12791801
TI  - Patterns and characteristics of ambulance attendance at heroin overdose at a
      local-area level in Melbourne, Australia: implications for service provision.
AB  - The monitoring of heroin use and related harms is undertaken in Australia with a
      view to inform policy responses. Some surveillance data on heroin-related harms
      is well suited to inform the planning and delivery of heroin-related services,
      such as needle and syringe provision. This article examines local-area variation
      in the characteristics of nonfatal heroin overdoses attended by ambulances in
      Melbourne over the period June 1998 to October 2000 to inform the delivery of
      services to the heroin-using population in Melbourne. Five so-called hot spot
      local government areas were considered in relation to the remainder of the
      Melbourne metropolitan area. Significant local-area variations in the
      characteristics of nonfatal heroin overdoses were evident over the study period,
      including the number of heroin overdoses, the age and sex of the people attended,
      the time of the attendance, the likelihood of hospitalization, and the likelihood
      of police coattendance. The implications of the findings are discussed in terms
      of service provision (e.g., opening hours) within the five hot spot local
      government areas, and it is argued that the analyses undertaken could easily be
      applied to other jurisdictions for which comparable data are available.

PMID- 12791802
TI  - Fatal heroin-related overdose in San Francisco, 1997-2000: a case for targeted
      intervention.
AB  - Heroin-related overdose is the single largest cause of accidental death in San
      Francisco. We examined demographic, location, nontoxicological, and toxicological
      characteristics of opiate overdose deaths in San Francisco, California. Medical
      examiner's case files for every opioid-positive death from July 1, 1997, to June
      30, 2000, were reviewed and classified as overdose deaths or other. Demographic
      variables were compared to two street-based studies of heroin users and to census
      data. From 1997 to 2000, of all heroin-related overdoses in San Francisco, 47%
      occurred in low-income residential hotels; 36% occurred in one small central area
      of the city. In 68% of deaths, the victim was reportedly alone. When others were
      present between last ingestion of heroin and death, appropriate responses were
      rare. In three cases, police arrested the person who called emergency services or
      others present on the scene. We recommend the development of overdose response
      training targeted at heroin users and those close to them, including the staff of
      residential hotels.

PMID- 12791803
TI  - Drug-related mortality and fatal overdose risk: pilot cohort study of heroin
      users recruited from specialist drug treatment sites in London.
AB  - Fatal overdose and drug-related mortality are key harms associated with heroin
      use, especially injecting drug use (IDU), and are a significant contribution to
      premature mortality among young adults. Routine mortality statistics tend to
      underreport the number of overdose deaths and do not reflect the wider causes of
      death associated with heroin use. Cohort studies could provide evidence for
      interpreting trends in routine mortality statistics and monitoring the
      effectiveness of strategies that aim to reduce drug-related deaths. We aimed to
      conduct a retrospective mortality cohort study of heroin users recruited from an
      anonymous reporting system from specialist drug clinics. Our focus was to test
      whether (1). specialist agencies would agree to participate with a mortality
      cohort study, (2). a sample could be recruited to achieve credible estimates of
      the mortality rate, and (3). ethical considerations could be met. In total, 881
      heroin users were recruited from 15 specialist drug agencies. The overall
      mortality rate of the cohort of heroin users was 1.6 (95% confidence interval
      [CI], 1.1 to 2.2) per 100 person-years. Mortality was higher among males, heroin
      users older than 30 years, and injectors, but not significantly higher after
      adjustment in a Cox proportional hazard model. Among the 33 deaths, 17 (52%) were
      certified from a heroin/methadone or opiate overdose, 4 (12%) from drug misuse, 4
      (12%) unascertained, and 8 (24%) unrelated to acute toxic effects of drug use.
      Overall, the overdose mortality rate was estimated to be at least 1.0 per 100
      person-years. The standardized mortality ratio (SMR) was 17 times higher for
      female and male heroin users in the cohort compared to mortality in the non
      heroin-using London population aged 15-59 years. The pilot study showed that
      these studies are feasible and ethical, and that specialist drug agencies could
      have a vital role to play in the monitoring of drug-related mortality.

PMID- 12791804
TI  - Preliminary evidence of health care provider support for naloxone prescription as
      overdose fatality prevention strategy in New York City.
AB  - Preliminary research suggests that naloxone (Narcan), a short-acting opiate
      antagonist, could be provided by prescription or distribution to heroin users to
      reduce the likelihood of fatality from overdose. We conducted a random postal
      survey of 1100 prescription-authorized health care providers in New York City to
      determine willingness to prescribe naloxone to patients at risk of an opiate
      overdose. Among 363 nurse practitioners, physicians, and physician assistants
      responding, 33.4% would consider prescribing naloxone, and 29.4% were unsure.
      This preliminary study suggests that a substantial number of New York City health
      care providers would prescribe naloxone for opiate overdose prevention.

PMID- 12791805
TI  - Attitudes about prescribing take-home naloxone to injection drug users for the
      management of heroin overdose: a survey of street-recruited injectors in the San
      Francisco Bay Area.
AB  - Naloxone, an injectable opiate antagonist, can immediately reverse an opiate
      overdose and prevent overdose death. We sought to determine injection drug users'
      (IDUs) attitudes about being prescribed take-home naloxone. During November 1999
      to February 2000, we surveyed 82 street-recruited IDUs from the San Francisco Bay
      Area of California who had experienced one or more heroin overdose events. We
      used a questionnaire that included structured and open-ended questions. Most
      respondents (89%) had witnessed an overdose, and 90% reported initially
      attempting lay remedies in an effort to help companions survive. Only 51%
      reported soliciting emergency assistance (calling 911) for the last witnessed
      overdose, with most hesitating due to fear of police involvement. Of IDUs
      surveyed, 87% were strongly in favor of participating in an overdose management
      training program to receive take-home naloxone and training in resuscitation
      techniques. Nevertheless, respondents expressed a variety of concerning
      attitudes. If provided naloxone, 35% predicted that they might feel comfortable
      using greater amounts of heroin, 62% might be less inclined to call 911 for an
      overdose, 30% might leave an overdose victim after naloxone resuscitation, and
      46% might not be able to dissuade the victim from using heroin again to alleviate
      withdrawal symptoms induced by naloxone. Prescribing take-home naloxone to IDUs
      with training in its use and in resuscitation techniques may represent a life
      saving, peer-based adjunct to accessing emergency services. Nevertheless,
      strategies for overcoming potential risks associated with the use of take-home
      naloxone would need to be emphasized in an overdose management training program.

PMID- 12791807
TI  - HIV/AIDS risk behaviors and correlates of injection drug use among drug users in
      Pakistan.
AB  - We studied prevalence and correlates of injection drug use, awareness of human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and risky
      behaviors among drug users serviced by a nongovernmental organization catering to
      drug users in three Pakistani cities (Quetta, Peshawar, and Rawalpindi). Logistic
      regression analysis was used to identify correlates of injection drug use. Of 608
      drug users, 99.8% were male; median age was 32 years, and 44% were married. Most
      (79.8%) were Pakistani; 15.3% were Afghani. The majority used heroin (98.7%),
      mostly by inhalation; 15.2% injected drugs. Only 41% had heard of HIV/AIDS, and
      30% had been paid for donating blood. Injection drug use and needle sharing were
      highest in Quetta. Injecting drug users (IDUs) were nearly twice as likely to
      have donated blood and to have heard about HIV/AIDS compared to other drug users.
      Interventions to discourage transitions to injection, increase HIV testing, and
      safeguard the blood supply in Pakistan are urgently needed.

PMID- 12791806
TI  - The impact of needle-exchange programs on the spread of HIV among injection drug
      users: a simulation study.
AB  - OBJECTIVE: To determine the impact of the implementation of a needle-exchange
      program (NEP) on the spread of human immunodeficiency virus (HIV) in an injection
      drug user (IDU) community. We conducted a Monte Carlo simulation study of a
      theoretical population of 10000 IDUs. The population was followed monthly from
      1984 to 2000. HIV was assumed to be transmitted only by needle sharing. The NEP
      was introduced in 1989 and evaluated over a period of 11 years. The impacts of
      the proportion of the population attending the NEP, the risk level of IDUs
      attending the NEP, the reduction in needle-sharing frequency, and the number of
      new needle-sharing partners acquired at the NEP on prevalence and incidence of
      HIV were determined. Increasing the proportion of the population who always
      attend the NEP and eliminating needle-sharing incidents among IDUs who always
      attended the NEP were the most effective ways of reducing the spread of HIV.
      Attracting high-risk users instead of lower risk users to the NEP also reduced
      the spread of HIV, but to a lesser extent. NEPs are effective at reducing the
      spread of HIV; even under the worst case scenario of low risk users more likely
      to attend the NEP, one additional partner per month as a result of attending the
      NEP, and poor NEP attendance, the estimated prevalence was still less than that
      from the scenario without an NEP. Under our model, NEPs were shown to reduce the
      spread of HIV significantly. Efforts should be focused on getting as many IDUs as
      possible to become regular NEP attenders and stop sharing needles rather than
      partially reducing the frequency of sharing by a larger number of IDUs.

PMID- 12791808
TI  - Secondary syringe exchange among injection drug users.
AB  - Syringe-exchange programs (SEPs) have proven to prevent the spread of bloodborne
      pathogens, primarily human immunodeficiency virus (HIV), among injection drug
      users (IDUs). In the United States, only about 7% of IDUs have access to and use
      SEPs. Some IDUs engage in secondary syringe exchange (SSE), meaning that one IDU
      (a "provider") obtains syringes at an SEP to distribute to other IDUs
      ("recipients"). This formative qualitative research was conducted to understand
      why and how IDUs engage in SSE to aid in the development of a large-scale peer
      HIV prevention intervention. Interviews with 47 IDUs in Oakland and Richmond,
      California, indicated that SSE was embedded in existing social networks, which
      provided natural opportunities for peer education. SSE providers reported a
      desire to help other IDUs as their primary motivation, while recipients reported
      convenience as their primary reason for using SSE. Building SSE into SEP
      structures can facilitate an effective provision of risk reduction supplies and
      information to IDUs who do not access SEPs directly.

PMID- 12791809
TI  - Consumption of fish from polluted waters by WIC participants in east Harlem.
AB  - To minimize exposure to neurotoxins such as mercury, polychlorinated biphenyls
      (PCBs), dioxins, and pesticide residues, the New York State Department of Health
      issues health advisories about consumption of certain fish and shellfish caught
      from polluted local waters. Fetal exposure causes cognitive developmental
      deficits in children. Consumption of fish was assessed. We surveyed 220 WIC
      (Special Supplemental Nutrition Program for Women, Infants, and Children)
      participants. Of the participants, 10% ate fish and shellfish caught in local
      polluted waters. Statistically significant factors associated with eating local,
      noncommercial fish included male gender and knowledge of the health advisory.
      Locally caught fish and crabs are consumed; thus, in utero and childhood exposure
      to these neurotoxins occurs. Interventions to promote safer choices of fish are
      needed.

PMID- 12791810
TI  - Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT.
AB  - The aim of this study was to do an initial assessment of the usefulness of 2beta
      carbomethoxy-3beta-(4-chlorophenyl)-8-(2-(18)F-fluoroethyl)nortropane ((18)F
      FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT)
      density in healthy humans and subjects with Parkinson's disease (PD). METHODS: We
      investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild
      unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with
      moderately severe bilateral disease. The healthy subjects underwent a 3-h PET
      scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while
      (18)F-FECNT was being injected over the first 5 min of the scan. Arterial blood
      samples were taken throughout scanning for well-counter and metabolite analysis
      to determine the presence of possible active metabolites. The scans were
      reconstructed; then we placed spheric regions of interest in the caudate nuclei,
      putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject.
      The radioactivity level in each region was calculated for each frame of a
      subject's PET scan. Then we calculated target tissue-to-cerebellum ratios for
      each time frame. RESULTS: The analysis of arterial blood samples revealed that
      metabolism of the tracer was rapid. The ether-extractable component of the
      arterial input was >98% pure (18)F-FECNT. The caudate nucleus and putamen
      exhibited the highest uptake and prolonged retention of the radioligand. They
      both attained maximum uptake at approximately 90 min, with the healthy subjects'
      average caudate- and putamen-to-cerebellum ratios (+/-SD) at that time being 9.0
      +/- 1.2 and 7.8 +/- 0.7, respectively. The maximal caudate-to-cerebellum ratios
      for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to
      cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD
      patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 +/-
      1.1 and a left ratio of 5.9 +/- 0.7 and an average right putamen-to cerebellum
      ratio of 2.8 +/- 0.1 and a left ratio of 3.0 +/- 0.6. The late-stage PD patients
      had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 +/- 0.4 and a
      left ratio of 3.9 +/- 0 and an average right putamen-to cerebellum ratio of 1.8
      +/- 0.1 and a left ratio of 1.8 +/- 0. CONCLUSION: These results indicate that
      (18)F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT
      system in humans. It has a much higher affinity for DAT than for the serotonin
      transporter and yields the highest peak striatum-to-cerebellum ratios and has
      among the most favorable kinetics of (18)F-radiolabeled DAT ligands. Having
      picked up presymptomatic changes in the hemisphere opposite the unaffected side
      of the body in our early-stage (unilateral) PD patients, it appears that, like
      other DAT radioligands, it may be able to identify presymptomatic PD.

PMID- 12791811
TI  - Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically
      induced disconnection in CADASIL: an 18F-FDG PET study.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by
      mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic
      lesions are largely confined to subcortical structures, whereas the cortex is
      spared. CADASIL, therefore, may serve as a model to study subcortically induced
      remote effects. The purpose of this study was to evaluate with (18)F-FDG PET
      whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in
      CADASIL patients and, if so, whether there is evidence of subcortically induced
      disconnection. METHODS: Eleven CADASIL patients (7 women, 4 men; mean age, 55.8
      +/- 6.7 y) without cortical lesions on brain MR images underwent PET after
      intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according
      to a previously published method. For further processing, patient studies were
      registered to a template of a healthy control group and region-of-interest-based
      and voxelwise comparisons were performed. RESULTS: In CADASIL patients, mean
      rCMRglc was significantly reduced in all cortical and subcortical structures,
      compared with the values in healthy volunteers. In the subcortical gray matter,
      metabolic rates, given as the percentage of the mean of healthy volunteers, were
      49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively.
      Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the
      frontal, parietal, temporal, and occipital lobes, respectively. On an individual
      level, most patients showed marked asymmetry and inhomogeneities of cortical
      glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed
      cerebellar diaschisis. CONCLUSION: This study showed that cortical glucose
      metabolism is significantly lower in CADASIL patients than in healthy volunteers.
      The observed decrease in rCMRglc may in part be explained by a reduction of
      cerebral blood flow and neuronal loss. In addition, our data provide evidence of
      remote effects secondary to the functional disruption of subcortical fiber tracts
      in this particular type of small-vessel disease.

PMID- 12791812
TI  - Serotonin transporters in the midbrain of Parkinson's disease patients: a study
      with 123I-beta-CIT SPECT.
AB  - In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest
      that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease
      process. The integrity of 5-HT transporters was assessed in PD patients with
      SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta
      CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters.
      METHODS: Forty-five PD patients at relatively early stages (mean Hoehn-Yahr
      stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15
      scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT
      system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated
      by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio
      (R(A)) method, and a modified graphic method that derives the ratio of ligand
      distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is
      equivalent to k(3)/k(4), was measured using the images acquired at 24 h after
      tracer injection. All measures were derived using the cerebellum as the reference
      region. RESULTS: In control subjects, the (123)I-beta-CIT activity in the
      midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a
      slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred
      at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and
      cerebellar activity were not significantly different from those in control
      subjects. None of midbrain R(PE), R(A), and R(V) was significantly different
      between control subjects and PD patients, whereas striatal V(3)" was bilaterally
      reduced in all patients, being 32% lower than that of the control subjects (P =
      0.002). In PD patients, none of the midbrain outcome measures was significantly
      correlated with either striatal V(3)" or motor or nonmotor symptom ratings,
      including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale
      scores. When the studies of 7 PD patients with depression were analyzed
      separately, none of the midbrain outcome measures in these patients either was
      different significantly from control values or correlated with the Hamilton
      Depression Rating Scale score. CONCLUSION: These results suggest that DA and 5-HT
      transporters are differentially affected in PD, and 5-HT transporters in the
      midbrain region may not be affected in relatively early stages of PD.
      Alternatively, 5-HT transporters in the remaining neurons may be upregulated,
      thus raising the midbrain 5-HT transporter density to almost normal levels.

PMID- 12791813
TI  - Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the
      assessment of myocardial viability.
AB  - During the noninvasive assessment of myocardial viability with (18)F-FDG
      metabolic imaging, adequate regulation of metabolic conditions is needed to
      ensure optimal image quality. The aim of this study was to compare the
      feasibility and image quality of cardiac (18)F-FDG SPECT imaging using acipimox
      in patients with diabetes and patients without diabetes. METHODS: Seventy
      patients with ischemic cardiomyopathy underwent (18)F-FDG SPECT using acipimox
      for the assessment of myocardial viability, followed by resting 2-dimensional
      echocardiography to identify dysfunctional myocardial tissue. The image quality
      was scored visually and quantitatively; the myocardium-to-background ratio was
      determined by region-of-interest analysis. The plasma concentrations of glucose
      and free fatty acids were determined to evaluate the metabolic conditions before
      and during (18)F-FDG imaging. RESULTS: Thirty-four patients had diabetes
      mellitus; of these, 12 had insulin-dependent diabetes mellitus and 22 had non
      insulin-dependent diabetes mellitus. The remaining 36 patients had no diabetes.
      During (18)F-FDG SPECT, no severe side effects occurred. Acipimox significantly
      lowered plasma levels of free fatty acids in both groups. Fifteen of 34 patients
      with diabetes had a plasma glucose level > 9 mmol/L, which was lowered
      successfully in all patients with additional insulin. Visual evaluation of the
      (18)F-FDG images showed good, moderate, and poor image quality in 27, 5, and 2
      patients, respectively, with diabetes mellitus and in 32, 4, and 0 patients,
      respectively, without diabetes (P = not statistically significant). The
      myocardium-to-background ratio of (18)F-FDG SPECT images was comparable in
      patients with and without diabetes mellitus (3.1 +/- 1.0 vs. 3.5 +/- 0.9, P = not
      statistically significant). The type of diabetes had no influence on (18)F-FDG
      image quality. CONCLUSION: (18)F-FDG SPECT metabolic imaging after acipimox is
      safe and practical for routine assessment of viability in patients with ischemic
      cardiomyopathy. Image quality is good, even in patients with diabetes, although
      additional insulin is sometimes needed.

PMID- 12791814
TI  - Addition of valsartan to an angiotensin-converting enzyme inhibitor improves
      cardiac sympathetic nerve activity and left ventricular function in patients with
      congestive heart failure.
AB  - We determined whether the addition of the angiotensin-receptor blocker valsartan
      to an angiotensin-converting enzyme (ACE) inhibitor improves cardiac sympathetic
      nerve activity and left ventricular function in patients with congestive heart
      failure (CHF). METHODS: Thirty-two patients with CHF (left ventricular ejection
      fraction [LVEF] < 40%; mean, 33% +/- 6%) were treated with an ACE inhibitor and a
      loop diuretic. Sixteen patients (group A) were randomized to additionally receive
      valsartan (40-80 mg/d), and the remaining 16 patients (group B) continued their
      current regimen. Patients were studied before and 6 mo after treatment. The
      delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score
      (TDS), and washout rate (WR) were determined from (123)I-metaiodobenzylguanidine
      images. The left ventricular end-diastolic volume (LVEDV) and LVEF were
      determined by echocardiography, and New York Heart Association (NYHA) functional
      class was estimated. RESULTS: Before treatment, TDS, H/M ratio, WR, LVEDV, LVEF,
      and NYHA functional class were similar in both groups. After treatment in group
      A, TDS decreased from 37 +/- 8 to 31 +/- 9 (P < 0.001), H/M ratio increased from
      1.66 +/- 0.23 to 1.81 +/- 0.23 (P < 0.001), and WR decreased from 47% +/- 9% to
      39% +/- 10% (P < 0.01). In addition, the LVEDV decreased from 193 +/- 36 mL to
      169 +/- 51 mL (P < 0.005), and LVEF increased from 32% +/- 7% to 41% +/- 13% (P =
      0.0005). In group B, these parameters did not change significantly. NYHA
      functional class improved in both groups (in group A, from 3.3 +/- 0.5 to 1.7 +/-
      0.6 [P < 0.0005]; in group B, from 3.3 +/- 0.5 to 2.4 +/- 0.6; [P < 0.005]). The
      improvement was significantly greater in group A than in group B (P < 0.05).
      CONCLUSION: The addition of valsartan to an ACE inhibitor improves cardiac
      sympathetic nerve activity, left ventricular function, and symptoms in patients
      with CHF.

PMID- 12791815
TI  - Validation of ultrafiltration as a method of measuring free 99mTc-MDP.
AB  - Quantitative studies of the kinetics of (99m)Tc-methylene diphosphonate ((99m)Tc
      MDP) in metastatic and metabolic bone disease require the measurement of free
      tracer in plasma to derive the input function. Several methods of measuring free
      (99m)Tc-MDP have been described including ultrafiltration, precipitation using
      trichloroacetic acid, and a direct in vivo measurement based on the assumption
      that free MDP is cleared through the kidneys by glomerular filtration. The aim of
      this study was to validate ultrafiltration as a convenient and accurate method of
      measuring the free fraction of (99m)Tc-MDP by comparing it with the glomerular
      filtration rate (GFR) method. A second aim was to measure the percentage of free
      (99m)Tc-MDP in a cross-section of patients using ultrafiltration to determine the
      interpatient variability and, therefore, whether individual measurements are
      required for bone kinetic studies. METHODS: In study 1, 10 volunteers (7 women, 3
      men; mean age, 37 y; range, 26-55 y) were injected with 3 MBq (99m)Tc-MDP and 3
      MBq (51)Cr-ethylenediaminetetraacetic acid, and multiple blood and urine samples
      were taken between 0 and 4 h. Plasma samples were spun in 5-, 10-, and 30-kDa
      filters and counted in a gamma-counter. In study 2, 51 randomly selected patients
      (26 women, 25 men; mean age, 66 y; range, 31-87 y) attending our department for a
      routine bone scan were injected with 600 MBq (99m)Tc-MDP, and 4 blood samples
      were taken between 0 and 4 h and spun in 10-kDa filters. RESULTS: In study 1, the
      mean percentages (+/-SD) of free (99m)Tc-MDP at 5 min and 4 h after injection
      measured using the 10-kDa filters were 83.1% +/- 3.4% and 44.0% +/- 10.0%. The
      mean ratios (+/-SEM) of the free (99m)Tc-MDP in ultrafiltrate compared with the
      GFR method for the 5-, 10-, and 30-kDa filters were 0.894 +/- 0.010, 0.943 +/-
      0.009, and 0.987 +/- 0.010. In study 2, the mean percentages (+/-SD) of free
      (99m)Tc-MDP at 15 min and 4 h were 75.3% +/- 8.0% and 48.8% +/- 9.5%, with a
      precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were
      significantly correlated with GFR but not with serum albumin. CONCLUSION:
      Ultrafiltration provides an accurate method of evaluating free (99m)Tc-MDP in
      plasma for bone kinetic studies. The results from both the healthy volunteers in
      study 1 and the patients in study 2 show that protein binding varied with time
      and showed significant differences between individuals that were partly dependent
      on GFR. It is thus necessary to measure individual protein binding values for
      bone kinetic studies.

PMID- 12791816
TI  - Increasing efficacy and safety of treatments of patients with well-differentiated
      thyroid carcinoma by measuring body retentions of 131I.
AB  - There is no consensus on the amount of (131)I for treatment of patients with well
      differentiated thyroid carcinoma; usual amounts vary widely. Body retention of
      (131)I has been shown to be a valuable index of radiation toxicity. If a broad
      range of body retentions occurs among patients, then high and low retentions will
      be a basis for modifying the usual prescriptions for (131)I to ensure safety and
      increase efficacy. METHODS: After withdrawal of thyroid hormone in 87 patients,
      the fractional retention of diagnostic (131)I in each body was measured at 2 d by
      a scintillation probe. In 43 patients, the retention was measured 2 d after
      therapeutic (131)I. RESULTS: Diagnostic retention varied from 0.01 to 0.51, with
      a median of 0.15. These retentions did not correlate with any index of health,
      thyroid hormone, or carcinoma status. Seventeen patients, previously treated with
      (131)I, exhibited a significantly lower mean retention. In 43 patients, retention
      of diagnostic (131)I was highly correlated with retention of therapeutic (131)I:
      diagnostic predicted therapeutic retention with a mean error of 0.04. In 10
      patients receiving thyroxine, the mean retention of diagnostic (131)I after
      recombinant human TSH (rhTSH) was strikingly lower, 0.06, with a range of 0.016
      0.16. CONCLUSION: Body retentions of (131)I are easily measured and vary
      considerably among patients. Because increased therapeutic (131)I will impart
      greater irradiation of tumor, and body retention has been accepted as an index of
      toxicity from (131)I, the use of body retention could enable prescriptions of
      therapeutic (131)I that enable increased efficacy while ensuring safety. If tumor
      retention is not proportionally decreased with the body retention of (131)I after
      rhTSH, then rhTSH may enable increased therapeutic efficacy.

PMID- 12791818
TI  - Skeletal scintigraphy of young patients with low-back pain and a lumbosacral
      transitional vertebra.
AB  - Lumbosacral transitional vertebrae can alter the biomechanics of weight transfer
      at the affected spinal segment. Low-back pain may result. This study assessed
      what skeletal scintigraphy reveals about stress associated with a lumbosacral
      transitional vertebra in young patients with low-back pain. METHODS: The study
      population included 48 patients (30 male, 18 female; age range, 6-19 y; mean age,
      15.7 y) with low-back pain and a lumbosacral transitional vertebra. Skeletal
      scintigraphy was correlated with plain radiographs in all, CT in 12, and MRI in
      11. RESULTS: High uptake was shown at the articulation between the transverse
      process of a lumbosacral transitional vertebra and the sacrum in 39 (81%) of the
      patients. In 23 (59%) of the 39 patients with high uptake, this finding was shown
      only by SPECT. In 13 (81%) of the 16 for which the high uptake was shown by
      planar imaging, the anterior projection was more valuable than the posterior
      projection. In 9 (23%) of the 39 patients with high uptake at the transverse
      sacral articulation, the lumbosacral transitional vertebra had not been noted in
      a radiographic report before skeletal scintigraphy but was identified through
      reevaluation or repetition of radiographs after skeletal scintigraphy.
      Radiographs showed sclerosis along the transverse-sacral articulation in only 8
      (21%) of the 39 patients with high uptake. Findings indicating stress or motion
      at the joint were shown by CT in 6 (55%) of 11 and by MRI in 5 (63%) of 8
      patients with high uptake at the transverse-sacral articulation who underwent
      these examinations. CONCLUSION: Skeletal scintigraphy often indicates stress at
      the transverse-sacral articulation of young patients with low-back pain and a
      lumbosacral transitional vertebra. Showing evidence of stress is best
      accomplished using SPECT. Changes are usually not radiographically evident, but
      there is a trend for MRI and CT to show findings that imply stress or motion at
      the articulation. The unique ability of skeletal scintigraphy to provide this
      physiologic information supports its use in these patients.

PMID- 12791817
TI  - Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a
      parathyroid adenoma.
AB  - The purpose of this prospective study was to evaluate the diagnostic value of
      early parathyroid SPECT combined with quantitative analysis as compared with
      planar imaging in patients undergoing minimally invasive radioguided surgery.
      METHODS: A total of 52 consecutive patients with primary hyperparathyroidism
      underwent planar and SPECT parathyroid scintigraphy 2-5 d before surgery. Each
      patient had a single-tracer dual-phase technique using (99m)Tc
      methoxyisobutylisonitrile ((99m)Tc-MIBI) and a double-tracer subtraction
      technique using a delayed (99m)Tc-pertechnetate scan. Immediately after the first
      (99m)Tc-MIBI planar image, a SPECT study was acquired. Before radioguided
      parathyroidectomy, each patient was reinjected with (99m)Tc-MIBI. Serum calcium
      levels were available for all patents before surgery and at 8 and 24 h after
      surgery. Serum parathyroid hormone (PTH) levels were also available for all
      patients. Quantitative analysis was performed using the average count ratio of
      parathyroid to left thyroid lobe, right thyroid lobe, and maximum thyroid
      activity. All patients had histopathologic examination of the removed glands.
      RESULTS: The average time for radioguided surgery was 30 min (range, 20-40 min).
      Postsurgical calcium levels correlated significantly with the adenoma weight (r =
      0.5; P = 0.016). Combined planar scintigraphy correctly identified 41 adenomas
      (79%). SPECT increased the sensitivity to 96%. SPECT was superior to planar
      imaging in 9 patients, mainly in patients with ectopic adenomas or with
      multinodular goiters. Gland size did not affect significantly the detectability
      of SPECT. (99m)Tc-MIBI retention was noted in only 31 adenomas (60%). The average
      uptake ratios of parathyroid counts to the left lobe, right lobe, and maximum
      thyroid activity were 1.20 +/- 0.42, 1.29 +/- 0.45, and 0.84 +/- 0.35,
      respectively. The latter ratio was significantly correlated with PTH levels
      before surgery (r = 0.408; P = 0.04). CONCLUSION: Our data indicate that early
      preoperative SPECT in patients with primary hyperparathyroidism is essential for
      accurate localization of parathyroid adenomas and for the selection of patients
      who are candidates for minimally invasive radioguided surgery. Planar parathyroid
      imaging is less sensitive compared with SPECT, and washout kinetics of (99m)Tc
      MIBI are unreliable in the dual-phase technique. Patients with higher presurgical
      PTH levels may especially benefit from radioguided surgery.

PMID- 12791819
TI  - Calf flow reserve with H(2)(15)O PET as a quantifiable index of lower extremity
      flow.
AB  - Objective measures of recruitable blood flow are of importance in angiogenesis
      trials. We validated a new PET-derived flow reserve (FR) measurement in healthy
      subjects and subjects with peripheral artery disease (PAD). METHODS: Five healthy
      volunteers and 5 subjects with PAD underwent cannulation of the femoral artery
      and vein. Basal and maximal flow (100 micro g/kg/min of adenosine infused
      intraarterially) in the lower extremity was determined using thermodilution (TD)
      techniques. Subjects then underwent plethysmography (PL) followed by PET
      measurements of blood flow at the calf level. For the PET studies, a transmission
      scan followed by injection of 1.85 GBq (50 mCi) H(2)(15)O and dynamic scanning
      for 5 min were acquired in five 1-min frames. Regions of interest were drawn on
      successive PET image slices, and radioactivity was quantified from the first
      minute scan after injection. FR for each of the 3 modalities was expressed as the
      ratio of adenosine to basal flow. RESULTS: PET-derived FR correlated strongly
      with TD (r = 0.82; P = 0.004) but not with PL (r = 0.17; P = 0.85). The mean
      average difference in FR between healthy volunteers and PAD subjects was 13.0
      with PET and 4.5 with TD. The intra- and intersubject variability for PET
      expressed as the coefficient of variation was 10.5% and 29.0% for healthy
      subjects and 7.0% and 52.9% in PAD, respectively. CONCLUSION: As expected, FR was
      significantly lower in PAD subjects compared with healthy subjects as assessed
      with TD and PET but not with PL. PET-derived FR appears to be reproducible and
      generates sharper and higher indices of recruitable flow in healthy subjects and
      PAD. These findings have implications for the use of PET-derived FR as a
      sensitive index of recruitable flow in angiogenesis trials.

PMID- 12791820
TI  - Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and
      sterile osteoarticular diseases.
AB  - Ciprofloxacin labeled with (99m)Tc specifically binds to various bacteria. Thus,
      it potentially constitutes a specific marker allowing discrimination between
      septic arthritis/osteomyelitis and aseptic osteoarticular diseases. The aim of
      this prospective study was to evaluate such properties in patients with skeletal
      diseases. METHODS: We prospectively investigated 2 groups of patients: patients
      with suspected osteoarticular infections (G1, n = 16) and a control group of
      patients with a presentation of osteoarticular diseases and no sign suggestive of
      infection (G2, n = 11). All had clinical, biologic, and radiologic evaluations
      and had 1-, 4-, and 24-h images from (99m)Tc-ciprofloxacin scintigraphy (370 MBq)
      before planned biopsy or surgery. For 23 patients, the scintigraphic results were
      compared with histologic and bacteriologic analyses of biopsy tissue samples; for
      4 patients, the scintigraphic results were compared with the findings from 23 +/-
      5 mo of follow-up. RESULTS: In G1, (99m)Tc-ciprofloxacin findings were true
      positive in all 11 infected sites, true-negative in 2 cases, and false-positive
      in 3. In G2, (99m)Tc-ciprofloxacin was true-negative in 4 cases and false
      positive in 7. Neither the location of (99m)Tc-ciprofloxacin activity nor its
      intensity or kinetics between 1, 4, and 24 h allowed discrimination between
      infection and aseptic diseases (sterile loosened joint replacement,
      pseudoarthrosis, or arthrosis). Sensitivity, specificity, and accuracy were 100%,
      37.5%, and 63%. CONCLUSION: (99m)Tc-Ciprofloxacin scintigraphy showed good
      sensitivity and a high negative predictive value for the detection of bone and
      joint infection, but it did not discriminate between infected and aseptic
      osteoarticular diseases in symptomatic patients referred for surgery.

PMID- 12791821
TI  - Nuclear medicine, the painful prosthetic joint, and orthopedic infection.

PMID- 12791822
TI  - PET imaging of osteosarcoma.
AB  - During the past decade the clinical value of PET imaging has been investigated
      for many different tumors. As knowledge of the advantages and limitations of this
      modality increased, PET has gained acceptance in tumor imaging. (18)F-FDG PET is
      now successfully used and approved for procedure reimbursement in many types of
      cancer-for example, lung cancer, melanoma, lymphoma, head and neck tumors, brain
      tumors, esophageal cancer, and colorectal cancer. In osteosarcoma, the
      introduction of neoadjuvant chemotherapy has dramatically improved survival
      rates, thus changing the demands for state-of-the-art imaging to provide detailed
      information on tumor staging and grading, evaluating treatment, and detecting
      recurrences. In this review, the available literature on PET imaging in
      osteosarcoma patients is critically summarized with respect to diagnosis,
      staging, therapy monitoring, and follow-up focusing on the clinically used
      tracers (18)F-FDG and (18)F-fluoride ion. Potential and probable indications are
      outlined. Because of the relatively small number of patients enrolled in clinical
      trials published to date, further research needs to be done in larger,
      prospective patient series to determine the full utility of PET in osteosarcoma.

PMID- 12791823
TI  - Expression of the hemochromatosis (HFE) gene modulates the cellular uptake of
      67Ga.
AB  - Recent studies have revealed that the wild-type hemochromatosis protein (HFE)
      interacts with the transferrin receptor (TfR) and modulates TfR-mediated iron
      uptake by cells. Because of similarities in the transport of gallium and iron and
      the use of (67)Ga scanning in lymphoid malignancies, we examined the effect of
      HFE expression on (67)Ga uptake. METHODS: (67)Ga and (59)Fe uptakes were measured
      in HeLa cells transfected with a FLAG-tagged wild-type HFE (fHFE) gene under
      control of a tetracycline-repressible promoter. fHFE and TfR protein levels were
      measured by Western blotting; cellular transferrin (Tf) binding sites were
      measured by (125)I-Tf binding assay. RESULTS: Induction of fHFE expression
      produced an increase in TfR protein that was accompanied by a decrease, rather
      than an increase, in cellular (67)Ga and (59)Fe uptake. The difference in (67)Ga
      uptake between fHFE-expressing and fHFE-nonexpressing cells was markedly
      increased in the presence of Tf. Although fHFE expression produced an increase in
      cellular TfR protein, cell surface and intracellular Tf binding sites were
      actually decreased in these cells. CONCLUSION: Our studies suggest that
      expression of wild-type HFE in cells produces a decrease in (67)Ga uptake due to
      a reduction in available Tf binding sites for (67)Ga-Tf on the TfR. These results
      imply that (67)Ga uptake by cells with wild-type HFE may differ from cells with
      the HFE C282Y mutation.

PMID- 12791824
TI  - Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human
      recombinant annexin V for human application.
AB  - 99mTc-hydrazinonicotinamido (HYNIC)-annexin V is a novel tracer for in vivo
      imaging of apoptosis. The present study on humans was performed to investigate
      the safety of (99m)Tc-HYNIC-annexin V and to quantify the biodistribution and
      radiation dose. METHODS: Six healthy, male volunteers participated in the study.
      A dual-head gamma camera was used to acquire conjugate anterior and posterior
      views. Imaging started with a transmission scan using a (57)Co-flood source to
      obtain a map of the local thickness of the volunteer. Approximately 250 MBq of
      (99m)Tc-HYNIC-annexin V were injected intravenously, directly followed by a 30
      min dynamic study. Whole-body scans were obtained at about 30 min, 3 h, 6 h, and
      24 h after injection. Organ uptake was determined after correction for
      background, scatter, and attenuation. The MIRDOSE3.1 program was used to
      calculate organ-absorbed doses and effective dose. Signs of adverse effects were
      investigated by monitoring renal and liver function, hematology, blood
      coagulation, and vital signs (blood pressure, pulse, respiration rate,
      temperature, and electrocardiogram). RESULTS: The kidneys accumulated 49.7 +/-
      8.1 percentage injected dose (%ID) at 3 h after injection; the liver, 13.1 +/-
      1.0 %ID; the red marrow, 9.2 +/- 1.8 %ID; and the spleen, 4.6 +/- 1.6 %ID. More
      than 90% of the blood activity was cleared with a half-life of 24 +/- 3 min. The
      biologic half-life of the activity registered over the total body was long (69 +/
      7 h). Excretion of the activity was almost exclusively through the urine (22.5
      +/- 3.5 %ID at 24 h), and hardly any activity was seen in the bowel or feces.
      Absorbed doses were found to be 196 +/- 31 micro Gy/MBq for the kidneys, 41 +/-
      12 micro Gy/MBq for the spleen, 16.9 +/- 1.3 micro Gy/MBq for the liver, and 8.4
      +/- 0.9 micro Gy/MBq for the red marrow. The effective dose was 11.0 +/- 0.8
      micro Sv/MBq, or 2.8 +/- 0.2 mSv for the average injected activity of 250 MBq. No
      adverse effects were observed. CONCLUSION: (99m)Tc-HYNIC-annexin V is a safe
      radiopharmaceutical, having a favorable biodistribution for imaging of apoptosis
      in the abdominal as well as thoracic area with an acceptable radiation dose.

PMID- 12791825
TI  - Dosimetry of 188Re-hydroxyethylidene diphosphonate in human prostate cancer
      skeletal metastases.
AB  - 188Re-Hydroxyethylidene diphosphonate ((188)Re-HEDP) was used in previous studies
      for the palliative treatment of metastatic bone pain. However, the kinetic and
      radiation-absorbed doses have not been well documented. Therefore, the aim of
      this study was to gather dosimetric data for (188)Re-HEDP. METHODS: Thirteen
      prostate cancer patients with skeletal involvement were treated with 2,700-3,459
      MBq (mean dose, 3,120 MBq) (188)Re-HEDP. Patients underwent whole-body scans 3,
      20, and 28 h after therapy. The effective half-life, residence time, and
      radiation-absorbed dose values were calculated for the whole body, bone marrow,
      kidneys, and bladder as well as for 29 bone metastases. The urinary excretion
      rate was determined in 6 urine samples of each patient collected over 48 h at 8-h
      intervals beginning immediately after the administration of (188)Re-HEDP. After
      injection of (188)Re-HEDP, blood samples were taken weekly for 6 wk, and platelet
      and leukocyte counts were performed. RESULTS: The mean effective half-life was
      15.9 +/- 3.5 h in bone metastases, 10.9 +/- 2.1 h in the bone marrow, 11.6 +/-
      2.1 h in the whole body, 12.7 +/- 2.2 h in the kidneys, and 7.7 +/- 3.4 h in the
      bladder. The following radiation-absorbed doses were calculated: 3.83 +/- 2.01
      mGy/MBq for bone metastases, 0.61 +/- 0.21 mGy/MBq for the bone marrow, 0.07 +/-
      0.02 mGy/MBq for the whole body, 0.71 +/- 0.22 mGy/MBq for the kidneys, and 0.99
      +/- 0.18 mGy/MBq for the bladder. (188)Re-HEDP showed a rapid urinary excretion
      within the first 8 h after therapy, with 41% of the (188)Re-HEDP administered
      being excreted. Forty-eight hours after therapy, the excretion rate was 60% +/-
      12%. Only 1 patient showed a decrease of platelet count below 100 x 10(9)
      counts/L. None of the patients presented with a decrease of leukocyte count below
      3.0 x 10(9) counts/L. CONCLUSION: (188)Re-HEDP is an effective
      radiopharmaceutical used in the palliative treatment of metastatic bone pain. The
      radiation-absorbed dose is acceptable for bone pain palliation with low doses for
      the normal bone marrow and the whole body.

PMID- 12791826
TI  - Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects.
AB  - This study was designed to evaluate the radiation dosimetry in human subjects for
      a new radiopharmaceutical, N-(3-(18)F-fluoropropyl)-2beta-carbomethoxy-3beta-(4
      iodophenyl)nortropane ((18)F-FPCIT). The goal was to determine a limiting dose
      consistent with accepted guidelines for use in clinical studies and to compare
      the radiation burden with other agents such as (123)I-FPCIT, (18)F-fluorodopa,
      and (18)F-FDG. METHODS: Dynamic PET scans of the urinary bladder were obtained in
      6 subjects; 2 subjects had brain scans and 5 subjects had scans of the thorax or
      abdomen. Regions of interest were placed over composite images of each organ for
      which activity was visualized to generate time-activity curves. Doses were
      calculated from residence times using the MIRDOSE3 program. RESULTS: The critical
      organ for dosimetry is the urinary bladder wall with a dose of 0.0586 +/- 0.0164
      mGy/MBq. The dose comes primarily (97.2%) from activity in the urinary bladder
      contents. The dose is lower than any of the other agents used commonly in PET to
      assess dopaminergic function. The effective dose equivalent (0.0120 mGy/MBq) is
      also lower than comparable compounds. CONCLUSION: (18)F-FPCIT has favorable
      dosimetry when compared with other agents used to study dopaminergic function.
      Doses as high as 853 MBq (23 mCi) may be given to adult patients and remain
      within accepted guidelines.

PMID- 12791827
TI  - Validation of gated blood-pool SPECT cardiac measurements tested using a
      biventricular dynamic physical phantom.
AB  - We have developed a biventricular dynamic physical cardiac phantom to test gated
      blood-pool (GBP) SPECT image-processing algorithms. Such phantoms provide
      absolute values against which to assess accuracy of both right and left computed
      ventricular volume and ejection fraction (EF) measurements. METHODS: Two silicon
      rubber chambers driven by 2 piston pumps simulated crescent-shaped right
      ventricles wrapped partway around ellopsoid left ventricles. Twenty experiments
      were performed at Ghent University, for which right and left ventricular true
      volume and EF ranges were 65-275 mL and 55-165 mL and 7%-49% and 12%-69%,
      respectively. Resulting 64 x 64 simulated GBP SPECT images acquired at 16 frames
      per R-R interval were sent to Columbia University, where 2 observers analyzed
      images independently of each other, without knowledge of true values. Algorithms
      automatically segmented right ventricular activity volumetrically from left
      ventricular activity. Automated valve planes, midventricular planes, and
      segmentation regions were presented to observers, who accepted these choices or
      modified them as necessary. One observer repeated measurements >1 mo later
      without reference to previous determinations. RESULTS: Linear correlation
      coefficients (r) of the mean of the 3 GBP SPECT observations versus true values
      for right and left ventricles were 0.80 and 0.94 for EF and 0.94 and 0.95 for
      volumes, respectively. Correlations for right and left ventricles were 0.97 and
      0.97 for EF and 0.96 and 0.89 for volumes, respectively, for interobserver
      agreement and 0.97 and 0.98 for EF and 0.96 and 0.90 for volumes, respectively,
      for intraobserver agreement. No trends were detected, though volumes and right
      ventricular EFs were significantly higher than true values. CONCLUSION: Overall,
      GBP SPECT measurements correlated strongly with true values. The phantom
      evaluated shows considerable promise for helping to guide algorithm developments
      for improved GBP SPECT accuracy.

PMID- 12791828
TI  - Increased MIBG uptake after transfer of the human norepinephrine transporter gene
      in rat hepatoma.
AB  - The transport of MIBG by the human norepinephrine transporter (hNET) seems to be
      the critical step in the treatment of MIBG-concentrating tumors. Therefore, we
      investigated whether the accumulation of MIBG may be induced by retroviral
      transfection of the hNET gene in Morris hepatoma cells. METHODS: A bicistronic
      retroviral vector for the transfer of the hNET coding sequence and the hygromycin
      resistance gene was generated. Morris hepatoma cells (MH3924A) were infected with
      the respective retroviral particles, and hNET-expressing cell lines MHhNEThyg1 to
      MHhNEThyg9 were obtained through hygromycin selection. The uptake of (3)H
      norepinephrine or (131)I-MIBG and the efflux of (131)I-MIBG were determined in
      transfected and wild-type cells. In addition, the (131)I-MIBG distribution was
      monitored in nude mice and rats bearing wild-type and hNET-expressing hepatomas.
      RESULTS: hNET-expressing hepatoma cell lines accumulated up to 36 times more
      norepinephrine than did wild-type cells and 8 times more than did hNET-expressing
      neuroblastoma cell line SK-N-SH. The addition of nisoxetine, a selective
      inhibitor of noradrenaline uptake, inhibited norepinephrine uptake. Maximal
      (131)I-MIBG accumulation was observed 2 h after incubation and was followed by
      43% efflux within 4 h after the (131)I-MIBG-containing medium had been removed.
      In vivo experiments performed with nude mice bearing both hNET-expressing and
      wild-type tumors showed a 10-fold-higher accumulation of (131)I-MIBG in
      transfected tumors than in wild-type tumors. The ex vivo calculations revealed
      doses of 605 and 75 mGy in hNET-expressing and wild-type tumor tissues,
      respectively. CONCLUSION: Transduction of the hNET gene enables Morris hepatoma
      cells to accumulate norepinephrine and MIBG. However, the retention of MIBG is
      brief; therefore, the absorbed dose of radiation in vivo is not expected to be
      therapeutically effective.

PMID- 12791829
TI  - Verapamil does not inhibit 99mTcN-NOET uptake in situ in normal or ischemic
      canine myocardium.
AB  - Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN
      NOET) is a new myocardial perfusion imaging agent currently undergoing phase III
      clinical trials in the United States and in Europe. (99m)TcN-NOET cellular uptake
      has been shown to be inhibited by the calcium channel inhibitor verapamil in
      cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ
      (99m)TcN-NOET myocardial uptake remains unknown. Therefore, the aim of this study
      was to evaluate whether the inhibitory effect of verapamil on the cellular uptake
      of (99m)TcN-NOET shown in vitro could be reproduced in situ in a canine model of
      normal and ischemic myocardium. METHODS: (99m)TcN-NOET uptake in normal and
      ischemic myocardium (70% flow reduction in the left anterior descending coronary
      artery) was measured in the absence or presence of verapamil (0.015 mg/kg/min x
      10 min) in anesthetized, open-chest dogs (n = 17). Control animals were infused
      with adenosine (0.2 mg/kg/min) to match the verapamil-induced increase in flow.
      RESULTS: By verapamil treatment, a clinically relevant plasma concentration of
      the calcium channel inhibitor was attained (mean +/- SEM, 290 +/- 152 ng/mL). In
      normal myocardium (n = 8), regional blood flow at the time of (99m)TcN-NOET
      injection was not statistically different in verapamil- and adenosine-treated
      dogs (1.69 +/- 0.03 vs. 1.61 +/- 0.04 mL/min/g, respectively). (99m)TcN-NOET
      uptake was slightly higher in the presence of verapamil (0.39 +/- 0.01 vs. 0.38
      +/- 0.01 counts per minute [cpm]/[Bq/kg]/g for adenosine; P = 0.04). However, no
      significant difference in (99m)TcN-NOET myocardial uptake was observed after
      normalization of the tracer uptake to regional myocardial blood flow. In ischemic
      myocardium (n = 9), regional blood flow was lower in verapamil-treated than in
      adenosine-treated animals (0.22 +/- 0.02 vs. 0.29 +/- 0.03 mL/min/g; P < 0.05).
      (99m)TcN-NOET uptake in the ischemic area was not inhibited by verapamil (0.09 +/
      0.01 vs. 0.10 +/- 0.01 cpm/[Bq/kg]/g; P = not significant). CONCLUSION:
      Verapamil does not inhibit (99m)TcN-NOET uptake in situ in normal and ischemic
      canine myocardium. These results suggest that verapamil should not affect
      (99m)TcN-NOET myocardial uptake in patients referred for myocardial perfusion
      imaging.

PMID- 12791830
TI  - Components of professional competence for nuclear medicine physicians.

PMID- 12791831
TI  - Methods to outline the patient during lymphoscintigraphy.

PMID- 12791832
TI  - Effect of acquisition orbit on SPECT in phantoms.

PMID- 12791833
TI  - Cardiac SPECT: 360 degrees circular acquisition may resolve defects of 180
      degrees data.

PMID- 12791834
TI  - Prognosis of primary osteosarcoma.

PMID- 12791835
TI  - Blood culture contamination: persisting problems and partial progress.

PMID- 12791836
TI  - Nationwide surveillance for Staphylococcus aureus with reduced susceptibility to
      vancomycin in Korea.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) accounts for more than 70% of
      S. aureus isolates from tertiary hospitals in Korea. Clinical isolates of S.
      aureus were collected from eight provincial, university-affiliated hospitals
      during the period from June 1999 to January 2001 for nationwide surveillance. All
      isolates were screened for reduced susceptibility to vancomycin by using brain
      heart infusion agar containing 4 micro g of vancomycin per milliliter. Population
      analysis and the determination of the MIC of vancomycin were done for the
      isolates which grew on the screening agar plates. Of 682 total isolates, MRSA
      accounted for 64% (439 of 682). Of 27 (4%) isolates that grew on the screening
      agar plates, none showed the heteroresistance phenotype. No strains with reduced
      susceptibility to vancomycin were identified.

PMID- 12791837
TI  - Longitudinal study of Salmonella enterica aerotype Typhimurium infection in three
      Danish farrow-to-finish swine herds.
AB  - A longitudinal study of the infection dynamics of Salmonella enterica was carried
      out with three Danish farrow-to-finish swine herds. To account for variations in
      Salmonella shedding over time, litters from each herd were divided into two
      cohorts. Each cohort consisted of 30 pigs, for a total of 180 pigs. Pigs were
      individually monitored by monthly bacteriologic and serologic examinations from
      weaning to slaughter. At weaning, individual sows were examined bacteriologically
      and serologically. At slaughter, cecal contents, ileocecal lymph nodes, and
      carcass swab samples were obtained from 131 pigs. A total of 88 pigs were found
      to be shedding Salmonella on one or more occasions. Only the Salmonella serotype
      Typhimurium was detected during the study period. At weaning, no sows or piglets
      were found to be shedding, but a serological reaction was detected in 11 sows.
      The prevalence in culture peaked in the nursery and subsequently declined to
      undetectable levels before slaughter. The seroprevalence peaked approximately 60
      days after the peak prevalence in culture. Salmonella was detected in individual
      fecal samples at least once in 53% of the pigs, and 62% of the pigs were
      seropositive more than once. Only 3.7% of all pigs were found to be culture
      positive on more than one occasion. Piglets from seroreacting sows had a
      significantly (P = 0.0339) lower probability of shedding in the nursery. Under
      the assumption that shedding lasted at least 1 or 2 weeks, the average shedding
      time was estimated to have been 18 or 26 days. An association between serology,
      on-farm bacteriology, and Salmonella prevalence in culture at slaughter was
      shown. Marked differences in prevalence in sera and prevalence in culture between
      cohorts and within herds were observed. These differences emphasize the need for
      caution when using point estimates in on-farm interventions and surveillance in
      subclinically infected swine herds.

PMID- 12791838
TI  - Prevalence of enteroaggregative Escherichia coli among children with and without
      diarrhea in Switzerland.
AB  - In a prospective study between July 1999 and September 2000, stool specimens of
      children below the age of 16 years with (n = 187) and without (n = 137) diarrhea
      were tested for the presence of enterovirulent bacteria by standard culture
      methods and by PCR. Targets for the PCR were the plasmid pCVD432 for
      enteroaggregative Escherichia coli (EAEC), the verotoxin 1 and verotoxin 2 genes
      for enterohemorrhagic E. coli, ipaH for enteroinvasive E. coli (EIEC) and
      Shigella spp., genes coding for heat-stable and heat-labile toxins for
      enterotoxigenic E. coli (ETEC), and the eaeA gene for enteropathogenic E. coli.
      The following bacteria could be associated with diarrhea: Salmonella enterica (P
      = 0.001), Campylobacter spp. (P = 0.036), ETEC (P = 0.012), and EAEC (P = 0.006).
      The detection of EAEC, ETEC, and S. enterica was strongly associated with a
      history of recent travel outside of Switzerland. EAEC isolates were found in the
      specimens of 19 (10.2%) of 187 children with diarrhea and in those of 3 (2.2%) of
      137 children without diarrhea (P = 0.006) and were the most frequently detected
      bacteria associated with diarrhea. Among the children below the age of 5 years,
      the specimens of 18 (11.9%) of 151 with diarrhea were positive for EAEC, while
      this agent was found in the specimens of 2 (2.2%) of 91 controls (P = 0.007).
      Enteropathogenic E. coli isolates were found in the specimens of 30 (16.4%) of
      the patients and in those of 15 (10.9%) of the controls, with similar frequencies
      in all age groups (P > 0.05). We conclude that EAEC bacteria are involved in a
      significant proportion of diarrhea cases among children. Children younger than 5
      years of age are more often affected by EAEC than older children.

PMID- 12791839
TI  - Diagnostic potential of parechovirus capsid proteins.
AB  - To study humoral and cellular immunity against human parechovirus type 1 (HPEV1),
      the viral capsid proteins VP0, VP1, and VP3 were expressed and purified as
      glutathione S-transferase (GST)-tagged recombinant proteins. The fusion proteins
      were used to raise antisera in rabbits. VP0 and VP1 antisera specifically
      detected HPEV1-infected cells in culture by immunoperoxidase staining and
      immunofluorescence. Furthermore, antisera against the VP0 and VP1 proteins had
      neutralizing effects against HPEV1 infection. When the HPEV1 antibody titers of
      20 adults and 55 children were determined by a microneutralization test, the
      prevalence of HPEV1 antibodies in the adult population was 96%, while 50% of
      children were seropositive. Selected sera were used to evaluate HPEV1 fusion
      proteins as antigens in an enzyme immunoassay. The VP3 capsid protein appeared to
      be suitable for the purpose, with specificity of 100% and sensitivity of 96%
      compared to the neutralization test. Furthermore, T-cell responses to the
      purified HPEV1 and HPEV1 capsid fusion proteins were studied in 20 adults. Sixty
      percent of the subjects had T-cell proliferation responses to purified HPEV1, and
      90% of the subjects also had positive T-cell responses to at least one of the GST
      capsid proteins.

PMID- 12791840
TI  - Studies of epidemiology and seroprevalence of bovine noroviruses in Germany.
AB  - Jena virus (JV) is a bovine enteric calicivirus that causes diarrhea in calves.
      The virus is approximately 30 nm in diameter and has a surface morphology similar
      to the human Norwalk virus. The genome sequence of JV was recently described, and
      the virus has been assigned to the genus Norovirus of the family CALICIVIRIDAE:
      In the present study, the JV capsid gene encoded by open reading frame 2 was
      cloned into the baculovirus transfer vector pFastBac 1, and this was used to
      transform Escherichia coli to generate a recombinant bacmid. Transfection of
      insect cells with the recombinant baculovirus DNA resulted in expression of the
      JV capsid protein. The recombinant JV capsid protein undergoes self-assembly into
      virus-like particles (VLPs) similar to JV virions in size and appearance. JV VLPs
      were released into the cell culture supernatant, concentrated, and then purified
      by CsCl equilibrium gradient centrifugation. Purified JV VLPs were used to
      hyperimmunize laboratory animals. An antigen capture enzyme-linked immunosorbent
      assay (ELISA) was developed and characterized initially with clinical specimens
      containing defined human noroviruses and bovine diarrheal samples from calves
      experimentally infected with JV; the ELISA was specific only for JV. The ELISA
      was used to screen 381 diarrheal samples collected from dairy herds in Thuringia,
      Hesse, and Bavaria, Germany, from 1999 to 2002; 34 of these samples (8.9%) were
      positive for JV infection. The unexpectedly high prevalence of JV was confirmed
      in a seroepidemiological study using 824 serum or plasma samples screened using
      an anti-JV ELISA, which showed that 99.1% of cattle from Thuringia have
      antibodies to JV.

PMID- 12791841
TI  - Molecular epidemiology of Vibrio cholerae O139 in China: polymorphism of
      ribotypes and CTX elements.
AB  - Vibrio cholerae O139, the second etiological serogroup of cholera, triggered the
      first outbreak of O139 cholera in China in 1993. To analyze the clone
      polymorphism of O139 isolates in China, 117 strains of V. cholerae O139, isolated
      from different areas in China between 1993 and 1999, were selected to
      characterize the phylogenetic relationships by molecular techniques. Analysis of
      restriction fragment length polymorphism in the conserved 16S rRNA gene revealed
      seven different ribotypes within the 117 strains. Among these strains, there were
      eight that lacked the cholera toxin gene (ctxAB), zot, and the repetitive
      sequence (RS); these eight strains belonged to three individual ribotypes. Our
      results suggested that V. cholerae O139 strains in China had clone diversity in
      phylogeny. The results of our hybridization patterns for CTX genetic elements
      (ctxAB, zot, and RS) showed that CTXPhi genomes in most V. cholerae O139 strains
      had two or more copies and had extensive restriction patterns even for the
      strains which belong to the same ribotype. For 22 (20.1%) strains, the copies of
      ctxAB were different from those of zot, suggesting that a ctxAB-negative CTXPhi
      genome may exist in O139 strains. This ctxAB-negative CTXPhi genome may coexist
      with the intact CTXPhi genome in a strain. In addition, the dendrogram for I-CeuI
      generated pulsed-field gel electrophoresis patterns showed that V. cholerae
      serogroup O139 has a closer relationship with one strain of serogroup O22 than
      with the strains of serogroup O1. The results of this study showed the clonal
      diversity and the distribution of O139 strains in China, suggesting multiple
      origins of the O139 cholera epidemic or sporadic events.

PMID- 12791843
TI  - Changing patterns of rotavirus genotypes in ghana: emergence of human rotavirus
      G9 as a major cause of diarrhea in children.
AB  - Genotyping of human rotaviruses was performed on 312 rotavirus-positive samples
      collected from 2,205 young children with diarrhea in the Upper East District of
      Ghana, a rural community. Of the 271 (86.9%) rotavirus strains that could be VP7
      (G) or VP4 (P) characterized, 73 (26.9%) were of G9 specificity. The predominant
      G9 genotype was G9P[8], which constituted 79.5% of all G9 strains detected,
      followed by G9P[6] (12.3%), G9P[10] (2.7%), and G9P[4] (1.3%). G9 strains with
      mixed P types constituted 2.7% of all G9 strains found in the study. All the
      G9P[8] strains had a long RNA electrophoretic pattern with VP6 subgroup II
      specificity. Four G9 isolates, GH1319, GH1416, GH3550, and GH3574, which were
      selected based on the abundance of stool material and were representative of the
      three electropherotypes observed, were cloned and sequenced. The Ghanaian
      isolates shared more than 98% sequence nucleotide homology with other G9 strains
      from the United States (US1205), Malawi (MW69), Brazil (R160), Japan (95H115),
      and Nigeria (Bulumkutu). However, they showed only 95% nucleotide homology with
      the Thai G9 strain Mc345. Phylogenetic analysis of the nucleic acid sequence
      revealed the existence of at least three clusters, with Ghanaian strains forming
      one cluster, Nigerian and Brazilian strains forming a second cluster, and U.S.,
      Malawian, and Japanese strains forming a third.

PMID- 12791842
TI  - Genetic variability among Group A and B respiratory syncytial virus isolates from
      a large referral hospital in New Delhi, India.
AB  - Respiratory syncytial virus (RSV) is an important childhood pathogen of acute
      lower respiratory infections in developed and developing countries. The molecular
      epidemiology of RSV in India is largely unknown. The present study was undertaken
      to standardize and evaluate reverse transcription-PCR (RT-PCR) for the rapid and
      simultaneous detection of RSV groups A and B in clinical samples and to study
      intragroup genetic variability. RT-PCR was evaluated by comparing the results of
      seminested RT-PCR with centrifugation-enhanced cultures on 200 nasopharyngeal
      aspirates from children with acute lower respiratory infections. RSV was isolated
      in 34 nasopharyngeal aspirates by centrifugation-enhanced cultures and identified
      in 45 samples by RT-PCR. In 15 samples RSV was identified by seminested RT-PCR
      alone and in four by centrifugation-enhanced cultures alone. Of the 45 samples
      positive for RSV by nested PCR, 15 belonged to group A, 29 to group B, and one
      sample suggested a mixed infection. Group B RSV predominated in both years of the
      2-year study. Genetic variability within RSV groups was studied by restriction
      fragment analysis of 35 PCR products. Among both group A and group B RSV, two
      different composite patterns were observed. Thus, RSV was found to be a major
      pathogen of acute lower respiratory tract infections in India, as it was detected
      in 24.5% of children by RT-PCR. RT-PCR provides a sensitive method for detection
      and typing of RSV group A and B viruses in clinical samples as well as a means to
      study intragroup variations. However, a higher sensitivity of detection of RSV in
      clinical samples can be obtained by its combination with additional techniques,
      such as virus cultivation.

PMID- 12791844
TI  - Rapid diagnosis of extrapulmonary tuberculosis by PCR: impact of sample
      preparation and DNA extraction.
AB  - In cases of suspected extrapulmonary tuberculosis, rapid and accurate laboratory
      diagnosis is of prime importance, since traditional techniques of detecting acid
      fast bacilli have limitations. The major difficulty with mycobacteria is
      achieving optimal cell lysis. Buffers used in commercial kits do not allow this
      complete lysis in a number of clinical specimens. A comparison of two sample
      preparation methods, pretreatment with proteinase K (PK-Roche) and complete DNA
      purification (cetyltrimethylammonium bromide [CTAB]-Roche), was conducted on 144
      extrapulmonary specimens collected from 120 patients to evaluate the impact on
      the Cobas-Amplicor method. Thirty patients were diagnosed with tuberculosis, with
      15 patients culture positive for Mycobacterium tuberculosis. Amplification and
      detection of the amplicons were impaired by a high number of inhibitory specimens
      (39 to 52%). CTAB-Roche allowed the detection of more culture-positive specimens
      by PCR than PK-Roche. Comparison with the final diagnoses of tuberculosis
      confirmed that CTAB-Roche produced the best sensitivity (53.8%) compared to
      culture (43.3%), PK-Roche (16%), and smear (13%). However, the specificity of the
      PCR assay with CTAB-Roche-extracted material was always lower (78.8%) than those
      with culture (100%) and PK-Roche (96.5%). False-positive specimens were lung
      biopsy material, lymph node biopsy material and aspirate, or bone marrow
      aspirate, mainly from immunocompromised patients. Despite the efficiency of
      complete DNA extraction for the rapid diagnosis by PCR of extrapulmonary
      tuberculosis, the false-positive results challenge our understanding of PCR
      results.

PMID- 12791845
TI  - Molecular characterization of ampicillin-resistant Enterococcus faecium isolates
      from hospitalized patients in Norway.
AB  - The genetic relationship of 81 ampicillin-resistant and 21 ampicillin-susceptible
      Enterococcus faecium isolates from clinical infections and rectal screening in
      hospitalized patients in Norway was studied by pulsed-field gel electrophoresis
      (PFGE) and amplified fragment length polymorphism (AFLP). PFGE showed 55
      different banding patterns, and 65 of the isolates could be grouped into one
      large group. With AFLP, 46 patterns were discerned, and 74 isolates clustered in
      one group. In general, the isolates had a higher degree of similarity than with
      PFGE. The purK gene, which is one of the targets of the E. faecium multilocus
      sequence typing scheme, was sequenced. Eleven different purK alleles could be
      discerned, with the majority of isolates (n = 80) harboring allele 1. With only
      two exceptions, all strains carrying purK-1 clustered in the same PFGE and AFLP
      groups, indicating a good correlation between PFGE type, AFLP type, and purK
      allele. Genetic polymorphism of a 571-bp PCR fragment of the C-terminal domain of
      the penicillin-binding protein 5 gene (pbp5) was determined, and sequence
      differences were associated with the level of ampicillin resistance. This study
      indicates that the majority of ampicillin-resistant E. faecium strains in Norway
      belong to a distinct genetic lineage of closely related genotypes. Rectal and
      clinical isolates were generally indistinguishable, and differences in clonal
      distribution and allele polymorphism were found mainly between ampicillin
      resistant and -susceptible isolates.

PMID- 12791847
TI  - Distribution of the secondary type III secretion system locus found in
      enterohemorrhagic Escherichia coli O157:H7 isolates among Shiga toxin-producing
      E. coli strains.
AB  - The ability of the complete genome sequence of enterohemorrhagic Escherichia coli
      O157 led to the identification of a 17-kb chromosomal region which contained a
      type III secretion system gene cluster at min 64.5. This locus contains open
      reading frames whose amino acid sequences show high degrees of similarity with
      those of proteins that make up the type III secretion apparatus, which is encoded
      by the inv-spa-prg locus on a Salmonella SPI-1 pathogenicity island. This locus
      was designated ETT2 (E. coli type III secretion 2) and consisted of the epr, epa,
      and eiv genes. ETT2 was found in enteropathogenic E. coli strains and also in
      some non-O157 Shiga toxin-producing E. coli (STEC) strains, but most of them
      contained a truncated portion of ETT2. Most O157 isolates had a complete
      collection of toxin-encoding genes eae and hlyA and the ETT2 locus, while most
      O26 strains had toxin-encoding genes eae and hlyA genes but an incomplete ETT2
      locus. Thus, an intact copy of ETT2 might mark a pathogenic distinction for
      particular STEC strains. Therefore, the presence of the ETT2 locus can be used
      for identification of truly pathogenic STEC strains and for molecular
      fingerprinting of the epidemic strains in humans and animals.

PMID- 12791846
TI  - Emergence of rifampin-resistant Rhodococcus equi with several types of mutations
      in the rpoB gene among AIDS patients in northern Thailand.
AB  - The antimicrobial susceptibilities of 30 Rhodococcus equi isolates obtained from
      30 patients between 1993 and 2001 in northern Thailand were investigated. The
      MICs showed a tendency toward resistance to various antibiotics but sensitivity
      to imipenem, minocycline, vancomycin, and teicoplanin (MICs, </=0.5 micro g/ml)
      and relative sensitivity to meropenem, clarithromycin, and ciprofloxacin (MICs,
      </=2 micro g/ml). Of the 30 isolates, 26 were susceptible (MICs, </=1 micro
      g/ml), 1 showed low-level resistance (MIC, 8 micro g/ml), and 3 showed high-level
      resistance (MICs, >/=64 micro g/ml) to rifampin. PCR amplification and DNA
      sequencing of the rpoB gene and molecular typing by pulsed-field gel
      electrophoresis (PFGE) were performed for eight R. equi isolates from eight AIDS
      patients with pneumonia or lung abscess caused by R. equi between 1998 and 2001,
      including one low- and three high-level rifampin-resistant isolates. As a result,
      two high-level rifampin-resistant strains with PFGE pattern A had a Ser531Trp
      (Escherichia coli numbering) mutation, and one high-level rifampin-resistant
      strain with PFGE pattern B had a His526Tyr mutation, whereas one low-level
      rifampin-resistant strain with PFGE pattern C had a Ser509Pro mutation. Four
      rifampin-susceptible strains with PFGE patterns D and E showed an absence of
      mutation in the rpoB region. Our results indicate the presence of several types
      of rifampin-resistant R. equi strains among AIDS patients in northern Thailand.

PMID- 12791848
TI  - The genus Aeromonas: biochemical characteristics, atypical reactions, and
      phenotypic identification schemes.
AB  - A total of 193 strains representing 14 different Aeromonas genomospecies were
      evaluated for 63 phenotypic properties to create useful tables for the reference
      identification of mesophilic aeromonads. Only 9 of 62 biochemical tests (14%)
      yielded uniform results, and the fermentation of certain carbohydrates was found
      to be linked to specific species. A number of unusual or aberrant properties for
      the genus Aeromonas were also detected in the collection of 428 strains (193 in
      the phenotypic study, 235 in a retrospective review). These tests included
      susceptibility to the vibriostatic agent, fermentation of m-inositol and D
      xylose, hydrolysis of urea, and the lack of cytochrome oxidase activity.
      Fermentation of melibiose was linked to raffinose fermentation in all Aeromonas
      species except A. jandaei. Keys are provided for clinical laboratories choosing
      to identify aeromonads to species level based upon initial Moeller decarboxylase
      and dihydrolase reactions. In addition, several new tests were identified that
      help to separate members of the A. caviae complex (A. caviae, A. media, and A.
      eucreonophila).

PMID- 12791849
TI  - Devices for rapid diagnosis of Malaria: evaluation of prototype assays that
      detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax
      specific antigen.
AB  - The ParaSight F test was developed as a pioneer industry effort in the large
      scale, process-controlled production of a device for the rapid diagnosis of
      malaria. This device performed well in field settings but was limited to the
      detection of a single malaria species, Plasmodium falciparum. The ParaSight F+V
      assay advanced upon the ParaSight F test format by incorporating a monoclonal
      antibody directed against a proprietary Plasmodium vivax-specific antigen, in
      addition to the antibody directed against P. falciparum histidine-rich protein 2,
      which was used in the ParaSight F assay. The modified assay was developed to add
      the capability to detect P. falciparum and P. vivax in a single-test-strip
      format. The present study evaluated three distinct ParaSight F+V prototypes with
      samples from symptomatic patients in regions of Thailand and Peru where malaria
      is endemic. Over a 2-year enrollment period (1998 and 1999), a total of 4,894
      patients consented to participation in the study. Compared with the results for
      duplicate microscopic examinations of Giemsa-stained blood smears as the
      reference diagnostic standard, each successive prototype showed substantial
      improvement in performance. The final ParaSight F+V prototype, evaluated in 1999,
      had an overall sensitivity for detection of asexual P. falciparum parasites of
      98%. The sensitivity of the device was 100% for P. falciparum densities of >500
      parasites/ micro l, with a sensitivity of 83% for parasite densities of </=500/
      micro l. The specificity for the exclusion of P. falciparum was 93%. For P.
      vivax, the overall sensitivity was 87% for the final 1999 prototype. The
      sensitivities calculated for different levels of P. vivax parasitemia were 99%
      for parasite densities of >5,000/ micro l, 92% for parasite densities of 1,001 to
      5,000/ micro l, 94% for parasite densities of 501 to 1,000/ micro l, and 55% for
      parasite densities of 1 to 500/ micro l. The specificity for the exclusion of P.
      vivax was 87%. The areas under the receiver operating characteristic curves for
      the diagnostic performance of the assay for the detection of P. falciparum and P.
      vivax were 0.8907 and 0.8522, respectively. These findings indicate that assays
      for rapid diagnosis have the potential to enhance diagnostic capabilities in
      those instances in which skilled microscopy is not readily available.

PMID- 12791850
TI  - Precise characterization of norovirus (Norwalk-like virus)-specific monoclonal
      antibodies with broad reactivity.
AB  - We have been characterizing monoclonal antibodies against Norovirus (Norwalk-like
      virus). In the course of our study, two monoclonal antibodies generated against
      Norovirus genogroup II capsid protein were found to react not only to genogroup
      II but also to genogroup I recombinant capsid proteins. In addition, we showed
      that these two monoclonal antibodies reacted to a 40-amino-acid-fragment located
      close to the N-terminal region of genogroup II Norovirus. Similar reactivity was
      observed with the equivalent region of genogroup I Norovirus. In this study, we
      confirmed that the epitopes of the two monoclonal antibodies existed within an 11
      amino-acid peptide. To obtain an idea of the reactive ranges of the two
      monoclonal antibodies toward different strains of Norovirus, their reactivities
      were investigated using 16 types of peptide constructed according to the data in
      GenBank and 8 recombinant capsid proteins (7 whole capsid proteins and 1 short
      [80-amino-acid] protein fragment). A characteristic broad reactivity of the two
      monoclonal antibodies is clearly shown by the results of this study. Thus, these
      monoclonal antibodies could be useful tools for detecting a broad range of
      Norovirus strains.

PMID- 12791851
TI  - The World Health Organization's External Quality Assurance System Proficiency
      Testing Program has improved the accuracy of antimicrobial susceptibility testing
      and reporting among participating laboratories using NCCLS methods.
AB  - A total of 150 laboratories in 33 countries that followed the NCCLS testing
      procedures participated in the World Health Organization's External Quality
      Assurance System for Antimicrobial Susceptibility Testing (EQAS-AST) from January
      1998 through March 2001. Laboratories tested seven bacterial isolates for
      antimicrobial resistance and reported the results to the Centers for Disease
      Control and Prevention (CDC) in Atlanta, Ga. The results were compared to the
      results generated at the CDC with the NCCLS broth microdilution and disk
      diffusion reference methods. Although there were few testing errors with
      Salmonella enterica subsp. enterica serovar Enteritidis, drugs that are not
      appropriate for therapy of Salmonella infections were tested and reported by 136
      (91%) of 150 laboratories. In addition, 29 (20%) of 150 laboratories used the
      Staphylococcus aureus breakpoints to report oxacillin results for Staphylococcus
      saprophyticus. For a vanB-containing Enterococcus faecalis strain, 124 (83%) of
      150 laboratories correctly reported vancomycin results that were +/-1 doubling
      dilution from the reference MIC or +/-3 mm from the reference disk diffusion
      result. Of the laboratories that tested Streptococcus agalactiae by disk
      diffusion, 17% reported nonsusceptible results for penicillin in error. While 110
      laboratories (73%) tested the S. pneumoniae challenge isolate against a
      fluoroquinolone, 83% tested it against ciprofloxacin, for which there are no
      NCCLS interpretive criteria. Ten of 12 laboratories testing levofloxacin and 4 of
      4 laboratories testing ofloxacin by an MIC method correctly reported resistant
      results for the isolate. Feedback letters sent to participating laboratories
      highlighted areas of susceptibility testing in individual laboratories that
      needed improvement. The positive impact of the feedback letters and the overall
      effectiveness of the EQAS program were documented in repeat testing challenges
      with pneumococci and staphylococci. The 31 and 19% increases in the numbers of
      laboratories using appropriate testing methods for pneumococci and staphylococci,
      respectively, in 2000 versus 1998 indicate that laboratory performance is
      improving.

PMID- 12791853
TI  - Survey of emm gene sequences from pharyngeal Streptococcus pyogenes isolates
      collected in Spain and their relationship with erythromycin susceptibility.
AB  - We conducted a nationwide survey of the variable 5' emm (M protein gene)
      sequences from 614 pharyngeal Streptococcus pyogenes isolates susceptible (299
      isolates) and resistant (315 isolates) to erythromycin that were isolated in
      Spain from 1996 to 1999. Almost 98% of these isolates had emm sequences in
      agreement with previously recorded M antigen association. We only identified a
      new 5' emm sequence in 17 isolates. Nine different emm types accounted for 85% of
      the S. pyogenes isolates susceptible to erythromycin. By contrast, only 3 emm
      types accounted for 70% of the erythromycin-resistant isolates. Further
      characterization of these isolates by ribotyping and pulsed-field gel
      electrophoresis indicated that high frequency of erythromycin resistance in Spain
      is due to few clones.

PMID- 12791852
TI  - Serotyping Streptococcus pneumoniae by multiplex PCR.
AB  - The capsule is a major virulence factor of pneumococci, and it was shown that
      some capsular variants are associated with antimicrobial resistance and certain
      types of disease. Moreover, pneumococcal capsular typing has received renewed
      interest since the availability of conjugate vaccines, which include serotypes
      frequently associated with pediatric disease. Our aim was to develop a simple,
      reliable, and economical method for detecting epidemiologically important
      serotypes present in the proposed 11-valent conjugate vaccine. We designed
      primers based on the sequences available for the capsular types 1, 3, 4, 6B, 14,
      18C, 19F, 19A, and 23F and combined them into seven multiplex PCRs. The method
      involves streamlined DNA template preparation and agarose gel electrophoresis to
      analyze the amplification products. A total of 446 pneumococci selected from
      among isolates colonizing the nasopharynx of children attending day care centers
      in Lisbon, Portugal, were typed both by conventional immunological techniques and
      by multiplex PCR. Capsular types identified by the PCR method invariably produced
      results concordant with the conventional serotyping technique. Even when the
      method presented does not fully type an isolate, the PCR data can guide the
      experimenter when using immunological serotyping. Multiplex PCR for the analysis
      of pneumococci provides an accurate, expeditious, and cost-effective way of
      reducing the number of strains that have to be serotyped by conventional
      immunological techniques.

PMID- 12791854
TI  - Controlled clinical comparison of BacT/ALERT standard aerobic medium with BACTEC
      standard aerobic medium for culturing blood.
AB  - Standard aerobic media are widely used for culturing blood with the BacT/ALERT
      (BioMerieux, Inc., Durham, N.C.) (BM) and BACTEC 9240 (BD Diagnostic Systems,
      Sparks, Md.) (BD) automated continuously monitoring instrument systems. Although
      similarly composed of soybean-casein digest broths, the formulations of the
      standard aerobic media available for these instruments differ from each other in
      supplements and in sodium polyanetholesulfonate concentration. Therefore, we
      compared the standard aerobic media available for these systems at two university
      hospitals. Blood samples from adult patients with suspected bloodstream infection
      were inoculated at the bedside into nonvented BM and BD standard aerobic blood
      culture bottles and incubated in their respective instruments. The laboratories
      received 6,743 pairs of bottles that were each filled with 8 to 12 ml of blood. A
      total of 523 isolates representing true infections were recovered from 257
      patients; of these isolates, 348 were recovered from both the BD and the BM
      bottles, 108 were recovered from the BM bottles only, and 67 were recovered from
      the BD bottles only (P < 0.005). More staphylococci (P < 0.05), especially
      coagulase-negative staphylococci (P < 0.05), and yeasts (P < 0.01) were recovered
      from BM bottles than from BD bottles. Of 291 unimicrobial episodes of bloodstream
      infection, 220 were detected with both bottles, 41 were detected with the BM
      bottles only, and 30 were detected with the BD bottles only (difference not
      significant). Among 335 cultures that were positive in both bottles within the
      first 72 h of incubation, the median times to detection were 14 h for BM bottles
      and 13 h for BD bottles. Rates for false-positive results were 0.5% for BM
      bottles and 0.1% for BD bottles. One BM bottle and seven BD bottles yielded false
      negative results. We conclude that the BM medium provides improved recovery of
      microorganisms, especially staphylococci and yeasts, compared with that provided
      by the BD medium.

PMID- 12791855
TI  - Several Salmonella enterica subsp. enterica serotype 4,5,12:i:- phage types
      isolated from swine samples originate from serotype typhimurium DT U302.
AB  - Pulsed-field gel electrophoresis, plasmid profiling, and phage typing were used
      to characterize and determine possible genetic relationships between 48
      Salmonella enterica subsp. enterica isolates of pig origin collected in
      Catalonia, Spain, from 1998 to 2000. The strains were grouped into 23 multidrug
      resistant fljB-lacking S. enterica serovar 4,5,12:i:- isolates, 24 S. enterica
      serovar Typhimurium isolates, and 1 S. enterica serovar 4,5,12:-:- isolate. After
      combining the XbaI and BlnI macrorestriction profiles (XB profile), we observed
      29 distinct subtypes which were grouped into seven main patterns. All 23 of the
      4,5,12:i:- serovar strains and 10 serovar Typhimurium isolates were found to have
      pattern AR, and similarities of >78% were detected among the subtypes. Three of
      the serovar Typhimurium DT U302 strains (strains T3, T4, and T8) were included in
      the same 4,5,12:i:- serovar cluster and shared a plasmid profile (profile I) and
      a pattern of multidrug resistance (resistance to ampicillin, chloramphenicol,
      streptomycin, sulfonamide, tetracycline, gentamicin, and trimethoprim
      sulfamethoxazole) commonly found in monophasic isolates. This led us to the
      conclusion that strains of the S. enterica 4,5,12:i:- serovar might have
      originated from an S. enterica serovar Typhimurium DT U302 strain.

PMID- 12791857
TI  - Development of group- and serotype-specific one-step SYBR green I-based real-time
      reverse transcription-PCR assay for dengue virus.
AB  - A quantitative one-step SYBR Green I-based reverse transcription (RT)-PCR system
      was developed for the detection and differentiation of four different dengue
      virus serotypes in acute-phase serum samples. A set of group- and serotype
      specific primer pairs was designed against conserved sequences in the core region
      and evaluated for clinical diagnosis. A linear relationship was obtained between
      the amount of input RNA and cycle threshold (Ct) value over a range of 10 to
      10(7) PFU per ml of cell culture-derived dengue viruses. The detection limit of
      the group-specific primer pair was between 4.1 and 43.5 PFU/ml for four dengue
      serotypes. The detection limit of each of the serotype-specific primer pairs was
      calculated to be 10 PFU/ml for dengue virus serotype 1 (DEN-1), 4.6 PFU/ml for
      DEN-2, 4.1 PFU/ml for DEN-3, and 5 PFU/ml for DEN-4. Comparisons between the one
      step SYBR Green-based RT-PCR assay and the conventional cell culture method in
      the clinical diagnosis of dengue virus infection from acute-phase serum samples
      of confirmed dengue patients were performed. The results showed that 83 and 67%
      of 193 acute-phase serum samples tested were positive by the one-step SYBR Green
      based RT-PCR method and cell culture method, respectively. Further analysis
      showed that the one-step SYBR Green-based RT-PCR method could detect twice as
      many acute-phase serum samples with positive dengue-specific immunoglobulin M
      (IgM) and/or IgG antibodies than cell culture method. Our results demonstrate the
      potential clinical application of the one-step SYBR Green I-based RT-PCR assay
      for the detection and differentiation of dengue virus RNA.

PMID- 12791856
TI  - Transient and persistent Helicobacter pylori colonization in Native American
      children.
AB  - Helicobacter pylori is chiefly acquired in childhood, but the exact timing of
      acquisition is not well understood. The main goal of this study was to assess H.
      pylori acquisition in a pediatric population. We studied two cohorts of Native
      American children: a birth cohort of 50 children and 58 older children (mean age,
      53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to
      H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort
      children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7
      (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children,
      49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori
      antibodies at study entry. During the next year, 7 (20.6%) children seroreverted,
      and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups,
      evaluation of CagA antibodies increased the sensitivity of H. pylori detection.
      Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly
      until age 6 months and remained constant for the next 19 months. At the time of
      H. pylori seroconversion, PGI peaked to levels significantly higher than in the
      never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but
      then declined to levels paralleling those of H. pylori-negative children. Thus,
      H. pylori acquisition, accompanied by a transient PGI increase, was frequent in
      this population, especially in the second and third years of life, but often was
      brief.

PMID- 12791858
TI  - Limitations of TaqMan PCR for detecting divergent viral pathogens illustrated by
      hepatitis A, B, C, and E viruses and human immunodeficiency virus.
AB  - Recent events illustrate the imperative to rapidly and accurately detect and
      identify pathogens during disease outbreaks, whether they are natural or
      engineered. Particularly for our primary goal of detecting bioterrorist releases,
      detection techniques must be both species-wide (capable of detecting all known
      strains of a given species) and species specific. Due to classification
      restrictions on the publication of data for species that may pose a bioterror
      threat, we illustrate the challenges of finding such assays using five nonthreat
      organisms that are nevertheless of public health concern: human immunodeficiency
      virus (HIV) and four species of hepatitis viruses. Fluorogenic probe-based PCR
      assays (TaqMan; Perkin-Elmer Corp., Applied Biosystems, Foster City, Calif.) may
      be sensitive, fast methods for the identification of species in which the genome
      is conserved among strains, such as hepatitis A virus. For species such as HIV,
      however, the strains are highly divergent. We use computational methods to show
      that nine TaqMan primer and probe sequences, or signatures, are needed to ensure
      that all strains will be detected, but this is an unfeasible number, considering
      the cost of TaqMan probes. Strains of hepatitis B, C, and E viruses show
      intermediate divergence, so that two to three TaqMan signatures are required to
      detect all strains of each virus. We conclude that for species such as hepatitis
      A virus with high levels of sequence conservation among strains, signatures can
      be found computationally for detection by the TaqMan assay, which is a sensitive,
      rapid, and cost-effective method. However, for species such as HIV with
      substantial genetic divergence among strains, the TaqMan assay becomes unfeasible
      and alternative detection methods may be required. We compare the TaqMan assay
      with some of the alternative nucleic acid-based detection techniques of
      microarray, chip, and bead technologies in terms of sensitivity, speed, and cost.

PMID- 12791859
TI  - Detection of Marek's disease virus DNA in chicken but not in human plasma.
AB  - Marek's disease virus (MDV) causes a common lymphomatous and neuropathic disease
      in domestic chickens and, less commonly, turkeys and quail. It is a member of the
      alpha-herpesviruses and until now was considered to be strongly cell associated.
      In 1991, MDV was suggested to be the causative infectious agent of multiple
      sclerosis (MS) in humans. In a previous study, we investigated the leukocytes of
      107 well-defined MS patients for the presence of MDV DNA but were unable to
      confirm a role for MDV in the pathogenesis of MS. A recent report (S. Laurent, E.
      Esnault, G. Dambrine, A. Goudeau, D. Choudat, and D. Rasschaert, J. Gen. Virol.
      82:233-240, 2001) described the detection of MDV DNA in 20% of 202 human serum
      samples, regardless of whether the individuals were exposed to poultry. The
      detection of MDV DNA in chicken serum samples was reported as well. The aim of
      the present study was to investigate whether we can confirm the presence of MDV
      DNA in chickens and humans if we use plasma as the source for nucleic acid
      isolation. Leukocytes and plasma specimens from 16 chickens experimentally
      infected with MDV serotype 1 and plasma specimens from 300 volunteer blood donors
      were tested for MDV DNA by two different TaqMan PCR assays. MDV DNA was
      repeatedly found in the leukocytes as well as in the plasma specimens of all 16
      animals. All human samples analyzed, however, tested negative by both assays.
      Accordingly, Marek's disease in chickens can be diagnosed by detection of MDV DNA
      in plasma as well as in leukocytes. Once again, we found no evidence for the
      spread of MDV to humans.

PMID- 12791860
TI  - Development of a heteroduplex mobility assay to identify field isolates of
      porcine reproductive and respiratory syndrome virus with nucleotide sequences
      closely related to those of modified live-attenuated vaccines.
AB  - Porcine reproductive and respiratory syndrome has been devastating the swine
      industry since the late 1980s. The disease has been controlled, to some extent,
      through the use of modified live-attenuated (MLV) vaccines once available.
      However, such a practice periodically resulted in isolation or detection of
      vaccine-like viruses from pigs as determined by a partial genomic sequencing. In
      this study, we developed a heteroduplex mobility assay (HMA) for quickly
      identifying porcine reproductive and respiratory syndrome virus (PRRSV) isolates
      with significant nucleotide sequence identities (>/=98%) with the modified live
      attenuated vaccines. The major envelope gene (ORF5) of 51 PRRSV field isolates
      recovered before and after the introduction of the vaccines was amplified,
      denatured, and reannealed with the HMA reference vaccine strains Ingelvac PRRS
      MLV and Ingelvac PRRS ATP, respectively. Nine of the 51 field isolates and the
      VR2332 parent virus of Ingelvac PRRS MLV, which were all highly related to
      Ingelvac PRRS MLV with </=2% nucleotide sequence divergence as determined by
      sequence analysis, were all identified by the HMA to form homoduplexes with the
      reference Ingelvac PRRS MLV. No homoduplex-forming field isolate was identified
      when Ingelvac PRRS ATP was used as the HMA reference except for its parent virus
      JA142. Other field isolates with more than 2% nucleotide sequence divergence with
      the respective reference vaccine strain resulted in the formation of
      heteroduplexes with reduced mobility in polyacrylamide gel electrophoresis. The
      HMA results also correlated well with the results of phylogenetic analyses. The
      data indicated that the HMA developed in the study may be a rapid and efficient
      method for large-scale screening of potential vaccine-like PRRSV field isolates
      for further genetic characterization.

PMID- 12791861
TI  - Comparison of commercial DNA extraction kits for extraction of bacterial genomic
      DNA from whole-blood samples.
AB  - The demand for molecular diagnostic tests in medical microbiology has highlighted
      the need for efficient methods of DNA extraction. In addition, it is preferable
      for these methods to be automated. An example of such a requirement is for the
      confirmation of meningococcal disease where rapid, sensitive, and specific
      procedures are required for public health management purposes. Previous studies
      have shown that whole blood is the preferred method for the isolation of
      bacterial DNA in meningococcal disease, and in this study, we compare five
      commercially available kits for the extraction of bacterial genomic DNA from
      whole-blood samples. These include kits in a 96-well binding plate, 96-well
      filter plate, and metallic bead formats. The method for all five kits is
      described, and the sensitivity, specificity, ease of automation, and overall
      efficiency are determined.

PMID- 12791862
TI  - Infection of a ventriculoatrial shunt with phenotypically variable Staphylococcus
      epidermidis masquerading as polymicrobial bacteremia due to various coagulase
      negative Staphylococci and Kocuria varians.
AB  - The diagnosis of bloodstream infection with coagulase-negative staphylococci is
      frequently based on the isolation of the same organism from more than one blood
      culture. Phenotypic variation is a common characteristic of pathogenic strains of
      Staphylococcus epidermidis which may affect species identification by the
      microbiology laboratory. We describe a patient with a new onset of nephritis and
      gram-positive bacteremia. Gram-positive cocci grew in multiple blood cultures and
      were identified by the Vitek 2 system as Kocuria varians, Staphylococcus hyicus,
      and S. epidermidis. Bacterial isolates grew on blood agar and Congo red agar
      plates as two distinct morphotypes and exhibited phenotypic variation. Neither
      morphotype could be identified by the API-Staph assay. Cellular fatty acid
      analysis identified one of the morphotypes as S. epidermidis but could not
      identify the other morphotype. All isolates were found to be identical by pulsed
      field gel electrophoresis, and both colonial morphotypes were identified as S.
      epidermidis by 16S ribosomal gene sequencing. Phenotypic variation of S.
      epidermidis may affect identification to the species level by phenotype-based
      identification systems. Caution should be exercised when differentiating between
      true infection and contamination based on strain identification.

PMID- 12791864
TI  - Evaluation of repetitive element sequence-based PCR as a molecular typing method
      for Clostridium difficile.
AB  - Repetitive element sequence-based PCR (rep-PCR) is a typing method that enables
      the generation of DNA fingerprinting that discriminates bacterial strains. In
      this study, we evaluated the applicability of rep-PCR in typing Clostridium
      difficile clinical isolates. The results obtained by rep-PCR were compared with
      those obtained by pulsed-field gel electrophoresis (PFGE) and PCR ribotyping. A
      high correspondence between pattern differentiations produced by rep-PCR and PFGE
      was observed, whereas PCR ribotyping showed a lower level of discriminatory
      power.

PMID- 12791863
TI  - Shiga toxin 1c-producing Escherichia coli strains: phenotypic and genetic
      characterization and association with human disease.
AB  - The distribution of the stx(1c) allele among Shiga toxin (Stx)-producing
      Escherichia coli (STEC) and the virulence characteristics of stx(1c)-harboring
      STEC are unknown. In this study, we identified stx(1c) in 76 (54.3%) of 140 eae
      negative, but in none of 155 eae-positive, human STEC isolates (P < 0.000001).
      The 76 stx(1c)-harboring E. coli isolates belonged to 22 serotypes, and each
      produced Stx1c as demonstrated by latex agglutination. Characterization of
      putative virulence factors demonstrated the presence of the locus of proteolysis
      activity (LPA) and the high-pathogenicity island in 65.8 and 21.1%, respectively,
      of the 76 Stx1c-producing E. coli isolates. Moreover, all but three of these
      strains contained saa, the gene encoding an STEC autoagglutinating adhesin. The
      virulence profiles of Stx1c-producing E. coli isolates were mostly serotype
      independent and heterogeneous. This enabled us to subtype the isolates within the
      same serotype. The individuals infected with Stx1c-producing E. coli strains were
      between 3 months and 72 years old (median age, 23.5 years) and usually had
      uncomplicated diarrhea or were asymptomatic. We conclude that Stx1c-producing E.
      coli strains represent a significant subset of eae-negative human STEC isolates,
      which belong to various serotypes and frequently possess LPA and saa as their
      putative virulence factors. The phenotypic and molecular characteristics
      determined in this study allow the subtyping of Stx1c-producing STEC in
      epidemiological and clinical studies.

PMID- 12791866
TI  - Quantitation of human immunodeficiency virus type 1 in breast milk.
AB  - The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in
      breast milk (BM) components remain largely unknown. Inhibitory effects, if any,
      of BM on HIV RNA and DNA PCR amplification are poorly understood. We have
      addressed these issues by using virus-spiked BM samples from HIV-negative women.
      BM samples from HIV-negative women were spiked with HIV-1 virions or cells
      containing a single integrated copy of HIV DNA (8E5/LAV). After incubation under
      different experimental conditions, viral RNA was detected by the Roche Amplicor
      UltraSensitive assay in whole-milk, skim milk, and lipid fractions. We found
      excellent correlation between HIV-1 input copy and recovery in whole milk (r =
      0.965, P < 0.0001), skim milk (r = 0.972, P < 0.0001), and the lipid fraction (r
      = 0.905, P < 0.001). PCR inhibition was observed in less than 10% of the spiked
      samples. Similar levels of inhibition were noted in BM samples collected from HIV
      infected women. HIV proviral DNA was detected in BM samples using real-time PCR
      (linear correlation between the threshold cycle versus log DNA copy number,
      >0.982). The effects of incubation duration and temperature and repeated freeze
      thaw cycles on HIV RNA recovery were analyzed. HIV RNA levels were remarkably
      stable in whole milk after three freeze-thaw cycles and for up to 30 h at room
      temperature. Our findings improve the understanding of the dynamics of HIV
      detection in BM and the conditions for BM sample collection, storage, and
      processing.

PMID- 12791865
TI  - Genetic relatedness of levofloxacin-nonsusceptible Streptococcus pneumoniae
      isolates from North America.
AB  - We characterized 32 levofloxacin-nonsusceptible Streptococcus pneumoniae (LNSP)
      isolates obtained from a broad geographic region of North America over a 5-year
      period by using capsular serotypes, antimicrobial susceptibility profiles, BOX
      PCR, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis
      (PFGE). Sixteen international clones identified by the Pneumococcal Molecular
      Epidemiology Network also were included for comparison. Fifteen serotypes were
      represented, with serogroups 6, 9, 14, 19, and 23 accounting for 63% of isolates.
      Among isolates whose quinolone resistance-determining regions were sequenced, all
      contained gyrA and parC point mutations. Sixty-three percent were penicillin
      susceptible, and 84% were erythromycin susceptible. BOX-PCR analysis identified
      39 different band patterns among 32 LNSP and 16 international clones and grouped
      16 isolates, including 2 international clones, into seven unrelated groups of 2
      to 4 isolates each. PFGE analysis identified 35 different band patterns among 32
      LNSP and 16 international clones and grouped 21 isolates, including 3
      international clones, into eight unrelated groups of 2 to 6 isolates each. MLST
      performed on 10 isolates identified five allelic profiles and separated 9
      isolates into four groups of 2 to 3 isolates each. Overall, each typing method
      indicated that the LNSP were heterogeneous and that resistance to
      fluoroquinolones was not closely associated with a particular serotype or with
      coresistance to other antimicrobial classes and suggests that LNSP have likely
      arisen through independent mutational events as a result of selective pressure.
      However, seven LNSP were found to be related to three international clones by
      PFGE.

PMID- 12791867
TI  - Identification by subtractive hybridization of a novel insertion element specific
      for two widespread Burkholderia cepacia genomovar III strains.
AB  - Species of the Burkholderia cepacia complex cause chronic and life-threatening
      infections in persons with cystic fibrosis. Epidemic strains infect multiple
      patients, reside primarily in genomovar III, and have an apparent enhanced
      capacity for human infection and/or interpatient transmission. By using
      subtractive hybridization, a novel insertion element, designated IS1363, was
      identified in epidemic strain PHDC, known to infect many cystic fibrosis patients
      in the mid-Atlantic region of the United States. IS1363 was also found in most
      isolates of the ET12 lineage, responsible for infecting large numbers of patients
      in Ontario, Canada, and the United Kingdom. Southern blot analysis demonstrated
      that whereas multiple copies of IS1363 were present in strain PHDC, only one copy
      was present in ET12 isolates. IS1363 was used to probe a collection of 943 B.
      cepacia complex isolates, representing all nine genomovars, recovered from 761
      cystic fibrosis patients or the natural environment. IS1363 was not found in
      other genomovar III strains and, with the exception of B. ambifaria, was absent
      from other B. cepacia complex species. Genotyping analyses of all IS1363-positive
      isolates demonstrated that strain PHDC was more widely distributed in the United
      States than previously appreciated; 212 cystic fibrosis patients in 24 states
      were identified as being infected with PHDC.

PMID- 12791868
TI  - Dissemination of SHV-12 and characterization of new AmpC-type beta-lactamase
      genes among clinical isolates of enterobacter species in Korea.
AB  - To determine the prevalence and genotype of an extended-spectrum beta-lactamase
      and new chromosomal AmpC beta-lactamases among clinical isolates of Enterobacter
      species, we performed antibiotic susceptibility testing, pI determination,
      induction tests, transconjugation, enterobacterial repetitive consensus (ERIC)
      PCR, sequencing, and phylogenetic analysis. Among the 51 clinical isolates
      collected from a university hospital in Korea, 6 isolates have been shown to
      produce SHV-12 and inducible AmpC beta-lactamases. These also included three
      isolates producing TEM-1b and one strain carrying TEM-1b and CMY-type beta
      lactamases with a pI of 8.0. The results from ERIC PCR revealed that six isolates
      were genetically unrelated, suggesting that dissemination of SHV-12 was
      responsible for the spread of resistance to extended-spectrum beta-lactams in
      Korea. Six genes of inducible AmpC beta-lactamases that are responsible for the
      resistance to cephamycins (cefoxitin and cefotetan), amoxicillin, cephalothin,
      and amoxicillin-clavulanic acid were cloned and characterized. A 1,165-bp DNA
      fragment containing the ampC genes was sequenced and found to have an open
      reading frame coding for a 381-amino-acid beta-lactamase. The nucleotide sequence
      of four ampC genes (bla(EcloK992004.1), bla(EcloK995120.1), bla(EcloK99230), and
      bla(EareK9911729)) shared considerable homology with that of AmpC-type class C
      beta-lactamase genes of gram-negative bacteria, especially that of the
      chromosomal ampC gene (bla(EcloMHN1)) of Enterobacter cloacae MHN1 (99.9, 99.7,
      99.6, and 99.6% identity, respectively). The sequences of two ampC genes
      (bla(EcloK9973) and bla(EcloK9914325)) showed close similarity to the chromosomal
      ampC gene (bla(EcloQ908R)) of E. cloacae Q908R (99.7% identity). The results from
      phylogenetic analysis suggested that six ampC genes could originate from
      bla(EcloMHN1) or bla(EcloQ908R).

PMID- 12791869
TI  - Rapid detection of vanA and vanB genes directly from clinical specimens and
      enrichment broths by real-time multiplex PCR assay.
AB  - A real-time PCR assay previously developed for use on the Roche LightCycler
      platform was investigated as an alternative to culture for the direct detection
      of vancomycin-resistant enterococci (VRE) in clinical specimens. PCR primers and
      fluorescence resonance energy transfer hybridization probes specific for the vanA
      and vanB genes were combined in a multiplex real-time PCR assay performed
      directly with fecal material obtained by rectal swabbing and with enrichment
      broth samples. DNA was prepared from the rectal swabs and enrichment broths with
      a commercially available DNA preparation column designed specifically for use
      with fecal specimens. One hundred eighty duplicate rectal swabs were obtained
      from 42 patients who were previously found to be positive for VRE and who were
      being monitored for carriage of VRE. Direct and enrichment broth cultures were
      performed with one swab, while PCR was performed with the other swab as well as
      any corresponding presumptive positive enrichment broth. In total, 100 specimens
      from 30 patients remained positive for VRE by at least one method. The multiplex
      real-time PCR was positive for 88 enrichment broths of rectal swabs from 27
      patients but for only 45 rectal swabs from 15 patients. Direct culture was
      positive for VRE for only 43 specimens from 11 patients, while enrichment broth
      culture was positive for VRE for 75 specimens from 22 patients. Inhibition
      studies for the multiplex real-time PCR assay, performed by spiking the DNA
      extracts from 50 negative rectal swabs and the corresponding enrichment broths
      with between 1 and 10 CFU of a VanB Enterococcus faecium strain, detected
      inhibition rates of 55.1 and 10%, respectively. PCR performed directly with
      enrichment broths was found to be significantly more sensitive than enrichment
      broth culture (P < 0.025). Negative samples were identified significantly earlier
      by PCR than by culture alone.

PMID- 12791870
TI  - High percentage of methicillin-resistant Staphylococcus aureus isolates with
      reduced susceptibility to glycopeptides in The Netherlands.
AB  - While testing the in vitro activities of 14 antimicrobial agents against 107
      methicillin-susceptible Staphylococcus aureus (MSSA) and 250 methicillin
      resistant S. aureus (MRSA) isolates collected in The Netherlands, we found to our
      surprise that 19 (7.6%) MRSA isolates were suspected of having reduced
      susceptibilities to the glycopeptides when the Etest system (AB Biodisk, Solna,
      Sweden) was used with a large inoculum (no. 2 McFarland standard) and an extended
      incubation time (48 h) on brain heart infusion agar for MIC testing. Eventually,
      15 of these isolates were classified as heterogeneously resistant to
      glycopeptides (heterogeneously glycopeptide-intermediate S. aureus [hGISA]
      isolates) according to the population analysis profile-area under the curve
      analysis. The MICs at which 50 and 90% of isolates are inhibited obtained with
      the Etest system with the large inoculum were as follows: for MSSA isolates, 3.0
      and 4.0 micro g/ml, respectively, for both teicoplanin and vancomycin; for MRSA
      isolates, 3.0 and 8.0 micro g/ml, respectively, for teicoplanin, and 3.0 and 4.0
      micro g/ml, respectively, for vancomycin. This is the first report of hGISA
      isolates in The Netherlands.

PMID- 12791871
TI  - Molecular analysis of human herpesvirus 8 by using single nucleotide
      polymorphisms in open reading frame 26.
AB  - Human herpesvirus 8 (HHV-8) can be classified into distinct subtypes on the basis
      of sequence polymorphisms in several open reading frames (ORFs). We analyzed the
      subtypes of HHV-8 in 59 human immunodeficiency virus-infected Japanese patients
      by using polymorphisms in ORF26 and found that over two-thirds of the HHV-8
      isolates fell into major subtype A. We also found that single nucleotide
      polymorphisms (SNPs) at nucleotide positions 1032 (C-to-A substitution) and 1055
      (G-to-T substitution) in HHV-8 ORF26 were correlated with increased
      susceptibility to Kaposi's sarcoma, compared to the results obtained with HHV-8
      with wild-type nucleotides at these positions (P = 0.0106). This observation
      suggests that molecular heterogeneity of the HHV-8 genome affects the biological
      properties of HHV-8, resulting in different clinical phenotypes of HHV-8
      infection. Since sensitive PCR of ORF26 allowed us to analyze the SNPs by using
      peripheral blood from HHV-8-infected patients, the ORF26 SNPs will be a potent
      tool for investigating the pathogenesis of HHV-8 infection.

PMID- 12791872
TI  - Analysis of genetic diversity of Streptococcus suis clinical isolates from pigs
      in Spain by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) was used to investigate the diversity of
      Streptococcus suis isolates of various serotypes recovered from swine clinical
      samples in Spain. Capsular types 9 (64.9%) and 2 (14.8%) were the most frequently
      isolated serotypes followed by serotype 7 (5.9%) and serotype 8 (4.3%). The PFGE
      results of this study with 60 different pulsotypes indicate a great genetic
      diversity among the S. suis isolates, which is consistent with the broad
      distribution of S. suis in the swine population. Forty-five percent of the
      pulsotypes corresponded to single isolates, no pulsotype was common to all farms,
      and at least 3 different pulsotypes were isolated in 56% of herds in which more
      than 3 clinical isolates were analyzed. These results reveal a great diversity
      both between and within herds throughout the strains of S. suis studied,
      demonstrating that different strains of S. suis are associated with infection in
      pigs. Some pulsotypes were more frequently isolated and exhibited a wider
      distribution over herds than others, and were the unique or predominant strains
      in several herds, suggesting the existence of a prevalent or a few prevalent
      clones responsible for a large proportion of clinical cases. Overall, the great
      genetic heterogeneity of the clinical strains of S. suis, the isolation of
      different strains within the same herd, and the predominance of particular
      strains in some herds are evidence that infection by S. suis is a dynamic process
      and reinforce the idea that the epidemiology of S. suis infection is very
      complex.

PMID- 12791873
TI  - A hospital-associated outbreak of Legionnaires' disease caused by Legionella
      pneumophila serogroup 1 is characterized by stable genetic fingerprinting but
      variable monoclonal antibody patterns.
AB  - An outbreak of 18 pneumonia cases caused by Legionella pneumophila serogroup 1
      occurred at a Swedish university hospital 1996 to 1999. Eight clinical isolates
      obtained by culture from the respiratory tract were compared to 20 environmental
      isolates from the hospital and to 21 epidemiologically unrelated isolates in
      Sweden, mostly from patients, by using pulsed-field gel electrophoresis (PFGE),
      amplified fragment length polymorphism analysis (AFLP), and monoclonal antibody
      (MAb) typing. All patients and most environmental isolates from the outbreak
      hospital belonged to the same genotypic cluster in both PFGE and AFLP. This
      genotype was distinctly different from other strains, including a cluster from a
      second hospital in a different part of the country. The MAb subtype of the
      outbreak clone was Knoxville except for three isolates that were Oxford. A
      variation in the MAb reactivity pattern was also found in a second genotypic
      cluster. These changes in the MAb reactivity pattern were due to the absence or
      presence of the lag-1 gene coding for an O-acetyltransferase that is responsible
      for expression of the lipopolysaccharide epitope recognized by MAb 3/1 of the
      Dresden Panel. In all MAb 3/1-positive strains, the lag-1 gene was present on a
      genetic element that was bordered by a direct repeat that showed a high degree of
      sequence homology. Due to this homology, the lag-1 gene region seemed to be an
      unstable element in the chromosome. MAb patterns are thus a valuable adjunct to
      genotyping methods in defining subgroups inside a genotypic cluster of L.
      pneumophila sg 1.

PMID- 12791874
TI  - General acquisition of human papillomavirus infections of skin occurs in early
      infancy.
AB  - The human skin papillomaviruses (HPVs) represent a group of ubiquitous viruses
      detected at a high prevalence in the normal skin of healthy adults. In the
      present study, we analyzed skin swab samples from babies during their first days
      of life and from infants at various ages up to age 4 years. Specimens from their
      parents and, for the newborn babies, environmental samples were also
      investigated. HPV DNA was already detected on the day of birth in samples from 2
      of the 16 babies, and 45% of the samples from the babies were positive for HPV in
      the days following birth. Seventy-seven percent of the skin samples collected
      from the mothers were HPV DNA positive. The prevalence of HPV DNA among children
      from the ages of 1 month to 4 years varied between 50 and 70%. The HPV DNA
      sequences detected revealed a great diversity of genotypes and putative
      genotypes. Among 115 samples from 38 infants and 31 parents and 7 environmental
      samples, a total of 73 HPV types or putative types were isolated. Of these, 26
      putative HPV types have not been described before. Our data suggest that
      asymptomatic HPV infections of normal skin are acquired very early in infancy and
      are caused by a great multiplicity of HPV types.

PMID- 12791875
TI  - Novel reporter T-cell line highly susceptible to both CCR5- and CXCR4-using human
      immunodeficiency virus type 1 and its application to drug susceptibility tests.
AB  - CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) is a major viral
      population that is transmitted by sexual intercourse and that replicates in
      infected individuals during the asymptomatic stage of HIV-1 infection, suggesting
      that agents effective against R5 HIV-1 can be expected to prevent viral
      transmission and delay disease progression. However, R5 HIV-1 is unable to
      replicate in human T-cell lines, which is an apparent obstacle to efficient and
      reliable susceptibility tests of compounds for their activities against R5 HIV-1.
      To establish a simple and rapid assay system for the monitoring of R5 HIV-1
      replication and drug susceptibility, we have established a novel reporter T-cell
      line, MOCHA (which represents MOLT-4 cells stably expressing CCR5 and carrying
      the HIV-1 long terminal repeat-driven secretory alkaline phosphatase). Cells of
      this cell line express CD4, CXCR4, and CCR5 on their surfaces and secrete human
      placental alkaline phosphatase into the culture supernatants during HIV-1
      infection. MOCHA cells proved to be highly permissive for the replication of R5
      HIV-1 as well as CXCR4-using (X4) HIV-1, and the alkaline phosphatase activity
      increased in parallel with increasing HIV-1 p24 antigen levels in the culture
      supernatants. When HIV-1 reverse transcriptase inhibitors, protease inhibitors,
      and entry inhibitors, including the CCR5 antagonist TAK-779 and the CXCR4
      antagonist AMD3100, were examined for their inhibitory effects on R5 and X4 HIV-1
      replication in MOCHA cells, the antiviral activities of these compounds were
      found to be almost identical to those previously reported in peripheral blood
      mononuclear cells. Thus, MOCHA cells are an extremely useful tool for detection
      of R5 and X4 HIV-1 replication and drug susceptibility tests.

PMID- 12791876
TI  - Characterization of Treponema phagedenis-like spirochetes isolated from
      papillomatous digital dermatitis lesions in dairy cattle.
AB  - Four spirochete strains were isolated from papillomatous digital dermatitis (PDD)
      lesions in Iowa dairy cattle and compared with two previously described
      spirochete strains isolated from dairy cattle in California. These six strains
      shared an identical 16S ribosomal DNA sequence that was 98% similar to Treponema
      phagedenis and 99% similar to the uncultivated PDD spirochete sequence DDLK-4.
      The whole-cell protein profiles resolved by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis of these six strains were similar. However, these strains
      showed differences in the antigenic diversity of lipopolysaccharide (LPS).
      Genetic diversity was also detected by pulsed-field gel electrophoresis of
      genomic DNA digests, revealing differences among five of the six strains. Serum
      immunoglobulin G antibodies from dairy cattle with active PDD lesions reacted
      with the LPS of all but one PDD spirochete strain. Likewise, peripheral blood
      mononuclear cells from cattle with active PDD lesions produced blastogenic
      responses to one of the two California isolates. Both antibody and lymphocyte
      blastogenic responses were reduced in convalescent dairy cattle, suggesting the
      immune response to these spirochetes has short duration. These results
      demonstrate genetic and antigenic diversity among T. phagedenis-like treponemes
      and provide further evidence for the involvement of these spirochetes in the
      pathogenesis of PDD.

PMID- 12791877
TI  - Multilocus sequence typing system for group B streptococcus.
AB  - A multilocus sequence typing (MLST) system was developed for group B
      streptococcus (GBS). The system was used to characterize a collection (n = 152)
      of globally and ecologically diverse human strains of GBS that included
      representatives of capsular serotypes Ia, Ib, II, III, V, VI, and VIII. Fragments
      (459 to 519 bp) of seven housekeeping genes were amplified by PCR for each strain
      and sequenced. The combination of alleles at the seven loci provided an allelic
      profile or sequence type (ST) for each strain. A subset of the strains were
      characterized by restriction digest patterning, and these results were highly
      congruent with those obtained with MLST. There were 29 STs, but 66% of isolates
      were assigned to four major STs. ST-1 and ST-19 were significantly associated
      with asymptomatic carriage, whereas ST-23 included both carried and invasive
      strains. All 44 isolates of ST-17 were serotype III clones, and this ST appeared
      to define a homogeneous clone that was strongly associated with neonatal invasive
      infections. The finding that isolates with different capsular serotypes had the
      same ST suggests that recombination occurs at the capsular locus. A web site for
      GBS MLST was set up and can be accessed at http://sagalactiae.mlst.net. The GBS
      MLST system offers investigators a valuable typing tool that will promote further
      investigation of the population biology of this organism.

PMID- 12791878
TI  - Species-specific identification of campylobacters by partial 16S rRNA gene
      sequencing.
AB  - Species-specific identification of campylobacters is problematic, primarily due
      to the absence of suitable biochemical assays and the existence of atypical
      strains. 16S rRNA gene (16S rDNA)-based identification of bacteria offers a
      possible alternative when phenotypic tests fail. Therefore, we evaluated the
      reliability of 16S rDNA sequencing for the species-specific identification of
      campylobacters. Sequence analyses were performed by using almost 94% of the
      complete 16S rRNA genes of 135 phenotypically characterized Campylobacter
      strains, including all known taxa of this genus. It was shown that 16S rDNA
      analysis enables specific identification of most Campylobacter species. The
      exception was a lack of discrimination among the taxa Campylobacter jejuni and C.
      coli and atypical C. lari strains, which shared identical or nearly identical 16S
      rDNA sequences. Subsequently, it was investigated whether partial 16S rDNA
      sequences are sufficient to determine species identity. Sequence alignments led
      to the identification of four 16S rDNA regions with high degrees of interspecies
      variation but with highly conserved sequence patterns within the respective
      species. A simple protocol based on the analysis of these sequence patterns was
      developed, which enabled the unambiguous identification of the majority of
      Campylobacter species. We recommend 16S rDNA sequence analysis as an effective,
      rapid procedure for the specific identification of campylobacters.

PMID- 12791879
TI  - Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients
      with pulmonary tuberculosis in Cameroon.
AB  - We analyzed DNA polymorphisms in 455 Mycobacterium tuberculosis complex isolates
      from 455 patients to evaluate the biodiversity of tubercle bacilli in Ouest
      province, Cameroon. The phenotypic and genotypic identification methods gave
      concordant results for 99.5% of M. tuberculosis isolates (413 strains) and for
      90% of Mycobacterium africanum isolates (41 strains). Mycobacterium bovis was
      isolated from only one patient. Analysis of regions of difference (RD4, RD9, and
      RD10) proved to be an accurate and rapid method of distinguishing between unusual
      members of the M. tuberculosis complex. Whereas M. africanum strains were the
      etiologic agent of tuberculosis in 56% of cases 3 decades ago, our results showed
      that these strains now account for just 9% of cases of tuberculosis. We
      identified a group of closely genetically related M. tuberculosis strains that
      are currently responsible for >40% of smear-positive pulmonary tuberculosis cases
      in this region of Cameroon. These strains shared a spoligotype lacking spacers
      23, 24, and 25 and had highly related IS6110 ligation-mediated (LM) PCR patterns.
      They were designated the "Cameroon family." We did not find any significant
      association between tuberculosis-causing species or strain families and patient
      characteristics (sex, age, and human immunodeficiency virus status). A comparison
      of the spoligotypes of the Cameroon strains with an international spoligotype
      database (SpolDB3) containing 11,708 patterns from >90 countries, showed that the
      predominant spoligotype in Cameroon was limited to West African countries (Benin,
      Senegal, and Ivory Coast) and to the Caribbean area.

PMID- 12791880
TI  - Diagnosis of pneumococcal pneumonia by psaA PCR analysis of lung aspirates from
      adult patients in Kenya.
AB  - psaA is the gene encoding pneumococcal surface adhesin A (PsaA), a 37-kDa protein
      expressed on the surface of Streptococcus pneumoniae. PCR primers for psaA have
      been shown to amplify the target DNA sequence in all 90 serotypes of S.
      pneumoniae and in none of 67 heterologous pathogens and colonizing bacteria of
      the upper respiratory tract. Pathogenic bacteria identified in lung aspirate
      specimens cannot normally be dismissed as contaminants or colonizers, which limit
      the assay specificity of other respiratory tract specimens. psaA PCR analysis was
      evaluated in 171 lung aspirates from Kenyan adults with acute pneumonia. The
      limit of detection was one genome equivalent. Sensitivity, estimated in 35
      culture-positive lung aspirates, was 0.83 (95% confidence interval, 0.70 to
      0.95). psaA PCR analysis extended the number of identifications of S. pneumoniae
      in lung aspirates from 35 on culture to 61 by both methods. Of 26 new
      pneumococcal diagnoses, 19 were corroborated by results of blood culture or urine
      antigen detection. Sequences of the PCR products from 12 positive samples were
      identical to the psaA target gene fragment. Using an internal control for the
      PCR, inhibition of psaA PCR was demonstrated in 17% (8 of 47) of false-negative
      specimens. The results of a control PCR for the human gene beta-actin suggested
      that false-negative psaA PCR results are attributable to problems of specimen
      collection, processing, or DNA extraction in 30% of cases (14 of 47). psaA PCR
      analysis is a sensitive tool for diagnosis of pneumococcal pneumonia in adults.

PMID- 12791881
TI  - Nocardia veterana as a pathogen in North American patients.
AB  - The molecular methodologies used in our laboratories have allowed us to define a
      group of Nocardia isolates from clinical samples which resemble the type strain
      of Nocardia veterana. Three patient isolates and the type strain of N. veterana
      gave identical and distinctive restriction fragment length polymorphisms (RFLPs)
      for an amplified portion of the 16S rRNA gene. These three isolates and the N.
      veterana type strain also gave identical RFLPs for an amplified portion of the 65
      kDa heat shock protein gene, but this pattern was identical to that obtained for
      the Nocardia nova type strain. Sequence analysis of both a 1,359-bp region of the
      16S rRNA gene and a 441-bp region of the heat shock protein gene of the patient
      isolates showed 100% identities with the same regions of the N. veterana type
      strain. DNA-DNA hybridization of the DNA of one of the patient isolates with the
      DNA of the N. veterana type strain showed a relative binding ratio of 82%, with
      0% divergence, confirming that the isolate was N. veterana. Biochemical and
      susceptibility testing showed no significant differences among the patient
      isolates and the N. veterana type strain. Significantly, the results of
      antimicrobial susceptibility testing obtained for our isolates were similar to
      those obtained for N. nova, indicating that susceptibility testing alone cannot
      discriminate between these species. We present two case studies which show that
      N. veterana is a causative agent of pulmonary disease in immunocompromised
      patients residing in North America. We also describe difficulties encountered in
      using 16S rRNA gene sequences alone for discrimination of N. veterana from the
      related species Nocardia africana and N. nova because of the very high degree of
      16S rRNA gene similarity among them.

PMID- 12791882
TI  - Comparative study using type strains and clinical and food isolates to examine
      hemolytic activity and occurrence of the cyl operon in enterococci.
AB  - The hemolytic ability, the presence of cyl genes, and the diagnostic accuracy of
      cytolysin molecular detection were investigated in the genus Enterococcus by
      using 164 strains from 20 different species (26 reference strains, 42 clinical
      isolates from human and veterinary origin, and 96 isolates from ewe cheese and
      milk). Hemolysis was assayed with sheep and horse erythrocytes and under aerobic
      or anaerobic conditions. Screening of cytolysin genes (cylL(L), cylL(S), cylM,
      cylB, and cylA) was performed with new specific primers and the anaerobic assay
      of beta-hemolysis was used as the "gold standard" for the evaluation of cyl gene
      based PCRs. Since beta-hemolysis and cyl genes were found in 10 and 14 species,
      respectively, the hemolytic ability seems to be spread throughout the genus
      ENTEROCOCCUS: Beta-hemolysis was observed in 6 of 26 (23%) reference strains, 14
      of 42 (33%) clinical isolates, and 6 of 96 (6%) food isolates. The presence of
      cyl genes was detected in 15 of 26 (58%) reference strains, 37 of 42 (88%)
      clinical isolates, and 67 of 96 (70%) food isolates. These data indicate a
      virulence potential in food isolates, reinforcing the need of their safety
      assessment. Analysis of phenotypic-genotypic congruence suggests a divergent
      sequence evolution of cyl genes and the effect of environmental factors in the
      regulation of cytolysin expression. Evaluation of the diagnostic accuracy of
      cytolysin molecular detection points to cylL(L)-based PCR and cylL(L)L(S)MBA
      based PCR as the most reliable approaches. Nevertheless, the low sensitivity
      (46%) and gene variability indicated by our study strongly recommend the
      phenotypic assay for the assessment of hemolytic ability in enterococci, followed
      by the molecular screening of cyl genes in nonhemolytic strains to evaluate their
      virulence potential.

PMID- 12791883
TI  - Characterization of the 8-kilodalton antigens of Taenia solium metacestodes and
      evaluation of their use in an enzyme-linked immunosorbent assay for
      serodiagnosis.
AB  - The Western blot for cysticercosis, which uses lentil lectin purified
      glycoprotein (LLGP) antigens extracted from the metacestode of Taenia solium, has
      been the "gold standard" serodiagnostic assay since it was first described in
      1989. We report that the diagnostic antigens at 14, 18, and 21 kDa, as well as
      some larger disulfide-bonded antigens, are actually all members of a very closely
      related family of proteins, the 8-kDa antigens. The genes for 18 unique, mature
      proteins have been identified. Nine of these were chemically synthesized and
      tested in an enzyme-linked immunosorbent assay with a battery of defined serum
      samples, including 32 cysticercosis-positive serum samples reactive with the 8
      kDa antigens of LLGP on Western blotting, 34 serum samples from patients with
      other parasitic infections, and 15 normal human serum samples. One of the 8-kDa
      antigens, TsRS1, is 100% sensitive and 100% specific. TsRS1 will be one component
      of a cocktail of three to four synthetic or recombinant antigens, based on the
      diagnostic bands of the Western blot, which will be used for the serodiagnosis of
      cysticercosis.

PMID- 12791884
TI  - Phenotypic description and antimicrobial susceptibilities of Aerococcus
      sanguinicola isolates from human clinical samples.
AB  - This report describes the clinical sources and phenotypic characterization of 16
      isolates of Aerococcus sanguinicola. Sixteen conventional tests were used to
      describe and differentiate the 16 isolates of A. sanguinicola from 30 strains of
      Aerococcus viridans, 27 strains of Aerococcus urinae, and a single strain each of
      Aerococcus christensenii and Aerococcus urinaehominis. The phenotypic
      characterizations of the type strains for each species and 14 A. sanguinicola
      isolates were also compared in the two reference laboratories. A. sanguinicola
      are catalase-negative, vancomycin-susceptible, gram-positive cocci arranged in
      clusters and tetrads, as are all Aerococcus species except A. christensenii
      (which is arranged in short chains). All 16 isolates of A. sanguinicola were
      leucine aminopeptidase and pyrrolidonylarylamidase positive, which is unique to
      this species among the aerococci. All A. sanguinicola isolates grew in broth
      containing 6.5% NaCl, hydrolyzed hippurate, and were variable in the bile-esculin
      test. None of the isolates deaminated arginine or were Voges-Proskauer positive.
      The type strain of A. sanguinicola was isolated from a blood culture of a patient
      living in Denmark. Seven additional isolates were from patients living in Canada,
      all with urinary tract infections (six were female). Eight isolates were from
      patients living in five different states in the United States; five were from
      patients with urinary tract infections, and three were from blood cultures of one
      patient each with pneumonia, suspected endocarditis, and unknown clinical
      conditions. The antimicrobial susceptibility patterns were unremarkable; all
      isolates tested were susceptible to penicillin, amoxicillin, cefotaxime,
      cefuroxime, erythromycin, chloramphenicol, vancomycin, quinupristin-dalfopristin
      (Synercid), rifampin, linezolid, and tetracycline. Six of the 15 cultures were
      resistant to ciprofloxacin and levofloxacin, but all 15 strains were susceptible
      to sparfloxacin. High-level resistance was detected for meropenem (2 strains) and
      trimethoprim-sulfamethonazole (1 strain). Intermediate resistance was detected
      for trimethoprim-sulfamethoxazole (10 strains) and clindamycin (3 strains).

PMID- 12791885
TI  - Prevalence of human T-lymphotropic virus type 1 among blood donors from Mashhad,
      Iran.
AB  - The city of Mashhad is the capital of Khorasan, the northeastern province of
      Iran, which has been recognized as an area where human T-lymphotropic virus type
      1 (HTLV-1) infection is endemic. All serum samples from blood donors are
      routinely screened for HTLV-1 by using enzyme-linked immunosorbent assay (ELISA).
      In the present study, 28,926 donors (81.86% male and 18.14% female) with a mean
      age of 32 years (range, 18 to 65 years) were screened in a 6 months period (July
      to December 1999). Of these donors in the primary screening, 228 (0.78%) tested
      positive by ELISA. The positive samples were confirmed by Western blot (WB)
      analysis. The WB results indicated that, of 228 positive ELISA specimens, 91.2%
      (208 specimens) were HTLV-1, 4.82% (11 specimens) were HTLV, 3.5% (8 specimens)
      were indeterminate, and 0.44% (1 specimen) was not confirmed. HTLV refers to
      samples in which the complete viral antigen banding patterns on WB strips were
      not present. In order to further evaluate the detection methodologies used, the
      HTLV-1-seropositive samples, the indeterminant samples, and/or HTLV samples were
      examined and confirmed by PCR. The HTLV samples were determined to be HTLV-1, the
      remaining samples were indeterminant, and the negative sample could not be
      confirmed for HTLV-1 by PCR. The prevalence of HTLV-1 infection in our study was
      0.77% among blood bank donors, which reconfirms the city of Mashhad as an area
      where the virus is endemic compared to other regions in the world. The incidence
      was correlated with increasing age, and it was higher in females than in males.

PMID- 12791887
TI  - Detection and identification of Mycobacterium species isolates by DNA microarray.
AB  - Rapid identification of Mycobacterium species isolates is necessary for the
      effective management of tuberculosis. Recently, analysis of DNA gyrase B subunit
      (gyrB) genes has been identified as a suitable means for the identification of
      bacterial species. We describe a microarray assay based on gyrB gene sequences
      that can be used for the identification of Mycobacteria species. Primers specific
      for a gyrB gene region common to all mycobacteria were synthesized and used for
      PCR amplification of DNA purified from clinical samples. A set of oligonucleotide
      probes for specific gyrB gene regions was developed for the identification of 14
      Mycobacterium species. Each probe was spotted onto a silylated glass slide with
      an arrayer and used for hybridization with fluorescently labeled RNA derived from
      amplified sample DNA to yield a pattern of positive spots. This microarray
      produced unique hybridization patterns for each species of mycobacteria and could
      differentiate closely related bacterial species. Moreover, the results
      corresponded well with those obtained by the conventional culture method for the
      detection of mycobacteria. We conclude that a gyrB-based microarray can rapidly
      detect and identify closely related mycobacterial species and may be useful in
      the diagnosis and effective management of tuberculosis.

PMID- 12791886
TI  - Antimicrobial susceptibility testing of porcine Brachyspira (Serpulina) species
      isolates.
AB  - No standardized method for susceptibility testing of Brachyspira spp. is
      currently available. A broth dilution procedure was evaluated and used to test
      the activities of six antimicrobial agents for 108 isolates of Swedish porcine
      Brachyspira spp. representing biochemical groups I, II, and III. Group I
      corresponds to Brachyspira hyodysenteriae, group II corresponds to B. intermedia,
      and group III corresponds to B. murdochii and B. innocens. A panel was designed
      with the antimicrobial agents dried in tissue culture trays with wells that
      allowed a liquid volume of 0.5 ml in each and agitation of the broth when
      incubated on a shaker. The MICs were determined by using brain heart infusion
      broth with 10% fetal calf serum. For 10 isolates, the results obtained in broth
      were compared to the MICs obtained on two different types of agar. Different
      inoculum densities and incubation times were also compared. The concentrations at
      which 90% of the B. hyodysenteriae isolates (n = 72) were inhibited in the broth
      dilution test by tiamulin (0.25 micro g/ml), tylosin (>256 micro g/ml),
      erythromycin (>256 micro g/ml), clindamycin (>4 micro g/ml), virginiamycin (4
      micro g/ml), and carbadox (0.06 micro g/ml) were determined. The MICs tended to
      be lower in broth than on agar. Differences in inoculum densities and incubation
      times had little influence on the MICs. The evaluated broth dilution test was
      simple to perform, the end points were easily read, and the results were
      reproducible and reliable. No isolates with decreased susceptibility to tiamulin
      were found among the Swedish isolates tested.

PMID- 12791888
TI  - Loop-mediated isothermal amplification for direct detection of Mycobacterium
      tuberculosis complex, M. avium, and M. intracellulare in sputum samples.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid
      amplification method in which reagents react under isothermal conditions with
      high specificity, efficiency, and rapidity. We used LAMP for detection of
      Mycobacterium tuberculosis complex, Mycobacterium avium, and Mycobacterium
      intracellulare directly from sputum specimens as well as for detection of culture
      isolates grown in a liquid medium (MGIT; Nippon Becton Dickinson Co., Ltd.,
      Tokyo, Japan) or on a solid medium (Ogawa's medium). Species-specific primers
      were designed by targeting the gyrB gene, and their specificities were validated
      on 24 mycobacterial species and 7 nonmycobacterial species. The whole procedure
      is quite simple, starting with the mixing of all reagents in a single tube,
      followed by an isothermal reaction during which the reaction mixture is held at
      63 degrees C. The resulting amplicons are visualized by adding SYBR Green I to
      the reaction tube. The only equipment needed for the amplification reaction is a
      regular laboratory water bath or heat block that furnishes a constant temperature
      of 63 degrees C. The assay had a detection limit of 5 to 50 copies of purified
      DNA with a 60-min incubation time. The reaction time could be shortened to 35 min
      for the species identification of M. tuberculosis complex, M. avium, and M.
      intracellulare from a solid-medium culture. Residual DNA lysates prepared for the
      Amplicor assay (Roche Diagnostics GmbH) from 66 sputum specimens were tested in
      the LAMP assay. Although the sample size used for the latter assay was small,
      2.75 micro l of the DNA lysates, it showed a performance comparable with that of
      the Amplicor assay, which required 50 micro l of the lysates. This LAMP-based
      assay is simple, rapid, and sensitive; a result is available in 35 min for a
      solid-medium culture and in 60 min for a liquid-medium culture or for a sputum
      specimen that contains a corresponding amount of DNA available for testing.

PMID- 12791889
TI  - Genetic diversity among clinical isolates of Acremonium strictum determined
      during an investigation of a fatal mycosis.
AB  - Primarily saprophytic in nature, fungi of the genus Acremonium are a well
      documented cause of mycetoma and other focal diseases. More recently, a number of
      Acremonium spp. have been implicated in invasive infections in the setting of
      severe immunosuppression. During the course of routine microbiological studies
      involving a case of fatal mycosis in a nonmyeloablative hematopoietic stem cell
      transplant patient, we identified a greater-than-expected variation among strains
      previously identified as Acremonium strictum by clinical microbiologists. Using
      DNA sequence analysis of the ribosomal DNA intergenic transcribed spacer (ITS)
      regions and the D1-D2 variable domain of the 28S ribosomal DNA gene (28S), the
      case isolate and four other clinical isolates phenotypically identified as A.
      strictum were found to have <99% homology to the A. strictum type strain, CBS
      346.70, at the ITS and 28S loci, while a sixth isolate phenotypically identified
      only as Acremonium sp. had >99% homology to the type strain at both loci. These
      results suggest that five out of the six clinical isolates belong to species
      other than A. strictum or that the A. strictum taxon is genetically diverse.
      Based upon these sequence data, the clinical isolates were placed into three
      genogroups.

PMID- 12791890
TI  - Direct isolation of Candida spp. from blood cultures on the chromogenic medium
      CHROMagar Candida.
AB  - CHROMagar Candida is a selective and differential chromogenic medium that has
      been shown to be useful for identification of Candida albicans, Candida krusei,
      Candida tropicalis, and perhaps Candida glabrata. Colony morphology and color
      have been well defined when CHROMagar Candida has been used to isolate yeast
      directly from clinical specimens, including stool, urine, respiratory, vaginal,
      oropharyngeal, and esophageal sources. Direct isolation of yeast on CHROMagar
      Candida from blood cultures has not been evaluated. We evaluated whether the
      color and colony characteristics produced by Candida spp. on CHROMagar Candida
      were altered when yeasts were isolated directly from blood cultures. Fifty
      clinical isolates of Candida were inoculated into aerobic and anaerobic blood
      culture bottles and incubated at 35 degrees C in an automated blood culture
      system. When growth was detected, an aliquot was removed and plated onto
      CHROMagar Candida. As a control, CHROMagar Candida plates were inoculated with
      the same isolate of yeast grown on Sabouraud dextrose agar simultaneously. No
      significant difference was detected in color or colony morphology between the
      blood and control isolates in any of the tested organisms. All C. albicans (n =
      12), C. tropicalis (n = 12), C. glabrata (n = 9), and C. krusei (n = 5) isolates
      exhibited the expected species-specific colony characteristics and color, whether
      isolated directly from blood or from control cultures. CHROMagar Candida can be
      reliably used for direct isolation of yeast from blood cultures. Direct isolation
      could allow mycology laboratories to more rapidly identify Candida spp., enable
      clinicians to more quickly make antifungal agent selections, and potentially
      decrease patient morbidity and mortality.

PMID- 12791892
TI  - Diversity of tn1546-like elements in vancomycin-resistant enterococci isolated
      from humans and poultry in Korea.
AB  - To investigate the possible spread of vancomycin resistance among enterococci
      through horizontal gene transfer between two sources of vancomycin-resistant
      enterococci (VRE) isolated from farm animals and humans in Korea, molecular
      characterization of VRE isolated from poultry (20 isolates) and humans (35
      isolates) was performed by PCR-restriction fragment length polymorphism typing of
      the vanA gene cluster (Tn1546). PCR mapping of Tn1546 finally distinguished seven
      different transposon types (types A to G). Type A was observed only in the
      poultry isolates, while the other six types were present only in the human
      isolates. An insertion sequence and deleted sequence were detected in most of the
      human isolates in the orf2-vanR and vanX-vanY regions in the Tn1546-like element,
      but not in the poultry isolates. Tn1546-like elements were found in conjugal
      plasmids of most human VRE, whereas they were detected in the chromosomes of all
      poultry VRE. Accordingly, no evidence was found of any recent transmission of
      vancomycin resistance genes between poultry and humans in Korea.

PMID- 12791891
TI  - Herpesvirus DNA is consistently detected in lungs of patients with idiopathic
      pulmonary fibrosis.
AB  - On the basis of earlier reports associating Epstein-Barr Virus (EBV) with half of
      the cases of idiopathic pulmonary fibrosis (IPF), we hypothesized that chronic
      infection with EBV or a closely related herpesvirus would be detected in all
      cases of IPF. We tested lung specimens from 33 IPF patients (8 patients with
      familial IPF and 25 patients with sporadic IPF) and 25 patients with other
      diseases as controls for the presence of eight herpesviruses using PCR-based
      techniques. One or more of four herpesviruses (cytomegalovirus [CMV], EBV, human
      herpesvirus 7 [HHV-7], and HHV-8) were detected in 32 of 33 (97%) subjects with
      IPF and in 9 of 25 (36%) controls (P < 0.0001). CMV, EBV, and HHV-8 were found
      more frequently in IPF patients than in controls (P < 0.05, P < 0.001, and P <
      0.01 respectively). Two or more herpesviruses were detected in 19 of 33 (57%) IPF
      patients and in 2 of 25 (8%) controls (P < 0.001). Two or more herpesviruses and
      HHV-8 were found more frequently in patients with sporadic IPF than in patients
      with familial IPF (P < 0.05 for both comparisons), and CMV was found less
      frequently in patients with sporadic IPF than in patients with familial IPF (P <
      0.05). Immunohistochemistry for EBV or HHV-8 antigen showed viral antigen
      primarily in airway epithelial cells. These data support the concept that a
      herpesvirus could be a source of chronic antigenic stimulation in IPF.

PMID- 12791893
TI  - Use of colony morphology to distinguish different enterococcal strains and
      species in mixed culture from clinical specimens.
AB  - Colony morphology on kanamycin esculin azide agar was investigated as a means of
      selecting different species and strains of enterococci from clinical specimens.
      Four representative colonies of each morphotype were indistinguishable by pulsed
      field gel electrophoresis, biotype, and antibiogram analysis. The optimum time
      for identification of different colony morphotypes was 72 h.

PMID- 12791894
TI  - Utility of an in-house mycobacteriophage-based assay for rapid detection of
      rifampin resistance in Mycobacterium tuberculosis clinical isolates.
AB  - A rapid in-house mycobacteriophage-based assay to identify multidrug resistance
      by detecting the rifampin susceptibility of Mycobacterium tuberculosis in a
      microtiter plate format was evaluated. The sensitivity, specificity, and overall
      accuracy of the assay were 100%. This test is rapid to perform and suitable for
      widespread implementation.

PMID- 12791895
TI  - Evaluation of the duopath verotoxin test for detection of shiga toxins in
      cultures of human stools.
AB  - The Duopath Verotoxin test (Merck KgaA, Darmstadt, Germany) is a newly developed
      immunochromatographic test for the confirmation of Shiga toxin (Stx)-producing
      Escherichia coli (STEC) strains from food products. This test detects both Stx 1
      (Stx1)-positive and Stx2-positive samples individually with the same device. By
      modification of the original protocol, the present study evaluated its
      performance and feasibility for clinical application with human stool samples,
      consisting of 41 frozen samples known to contain STEC isolates (O157:H7 and non
      O157 serotypes) and 250 fresh specimens. The test specimens were polymyxin B
      extracts of colony sweeps taken from overnight sorbitol-MacConkey agar cultures
      of stools containing STEC isolates and other bacteria. All 41 frozen STEC
      positive stool samples were positive by the Duopath Verotoxin test, as were 2
      fresh stool samples with culture-confirmed STEC O157 infection. Thus, 100%
      sensitivity and no false-positive results were obtained when the Premier EHEC
      assay (Meridian Bioscience, Cincinnati, Ohio) was used as the "gold standard."
      The Duopath Verotoxin test is simple to perform and easy to interpret, providing
      a turnaround time of 24 h. Despite its original intended use, the Duopath
      Verotoxin test has a great potential for clinical application.

PMID- 12791896
TI  - Ischemic stroke and splenic rupture in a case of Streptococcus bovis
      endocarditis.
AB  - A 58-year-old man with an acute stroke suffered from splenic rupture.
      Streptococcus bovis was found in blood cultures, and gram-negative cocci were
      found in the infarcted spleen. Hemorrhagic transformation of the stroke occurred.
      Echocardiography showed aortic endocarditis. Cardiac surgery was not performed
      because of concern about cerebral bleeding. The patient died due to cerebral
      rehemorrhage after 3 weeks.

PMID- 12791897
TI  - Molecular epidemiology of macrolide resistance in neonatal bloodstream isolates
      of group B streptococci.
AB  - Pulsed-field gel electrophoresis (PFGE) was performed on 122 neonatal bloodstream
      isolates of group B streptococci (GBS) to further examine the relationship
      between macrolide resistance and serotype V GBS (GBS-V). Over one-third (35%) of
      macrolide-resistant GBS belonged to a single PFGE subtype of GBS-V, which was
      also the most common GBS-V subtype noted in previous Centers for Disease Control
      and Prevention surveillance studies. Erm methylase (ermA and ermB) was the most
      common resistance mechanism detected, present in 12 of 20 macrolide-resistant
      GBS.

PMID- 12791898
TI  - Comparison of washing and swabbing procedures for collecting genital fluids to
      assess cervicovaginal shedding of herpes simplex virus type 2 DNA.
AB  - Asymptomatic genital shedding of herpes simplex virus type 2 (HSV-2) DNA was
      evidenced by real-time PCR in 25 (13.2%) of 188 cervicovaginal lavage samples and
      in only 13 (6.9%) paired cervicovaginal samples from 188 HSV-2-seropositive,
      nonpregnant childbearing-aged human immunodeficiency virus-seronegative women
      living in Gabon. These observations demonstrate that cervicovaginal washing is
      more suitable than endocervicovaginal swabbing for detecting and quantifying HSV
      2 DNA by PCR in female genital secretions.

PMID- 12791899
TI  - Comparison of results obtained by testing with three different agar media and by
      the NCCLS M27-A method for in vitro testing of fluconazole against Candida spp.
AB  - Fluconazole susceptibilities of 150 Candida isolates were determined by a 25-
      micro g fluconazole disk diffusion agar test and compared with the microdilution
      NCCLS M27-A method. The agar test used three different media and was read at 24
      and 48 h. When only the susceptible and nonsusceptible categories were used, disk
      diffusion with Mueller-Hinton agar supplemented with 2% glucose and 0.5 micro g
      of methylene blue (MHGM) per ml had a 95.37% correlation with the MIC method at
      24 h, followed by RPMI 1640-2% of glucose agar (correlation, 94%) and Shadomy
      medium (SHDM) (correlation, 92.6%). The growth of microcolonies inside the
      inhibition zones was common (>63%) in the RPMI and SHDM media and minimal with
      MHGM (8.7%). At 48 h, MHGM and SHDM still had a >91% correlation with the MIC,
      while RPMI results had dropped to 75%. The best overall agreement was obtained
      with C. dubliniensis (100%).

PMID- 12791900
TI  - Multiplex PCR assay for identification of human diarrheagenic Escherichia coli.
AB  - A multiplex PCR assay for the identification of human diarrheagenic Escherichia
      coli was developed. The targets selected for each category were eae for
      enteropathogenic E. coli, stx for Shiga toxin-producing E. coli, elt and est for
      enterotoxigenic E. coli, ipaH for enteroinvasive E. coli, and aggR for
      enteroaggregative E. coli. This assay allowed the categorization of a
      diarrheagenic E. coli strain in a single reaction tube.

PMID- 12791901
TI  - Evaluation of genotype MTBC assay for differentiation of clinical Mycobacterium
      tuberculosis complex isolates.
AB  - A commercially available DNA strip assay was evaluated for the ability to
      differentiate Mycobacterium tuberculosis complex species. M. bovis subsp. bovis,
      M. bovis subsp. caprae, M. bovis BCG, M. africanum subtype I, and M. microti were
      unequivocally identified. M. tuberculosis, M. canetti, and M. africanum subtype
      II showed a unique hybridization pattern.

PMID- 12791903
TI  - Increased prevalence of G1P[4] genotype among children with rotavirus-associated
      gastroenteritis in metropolitan Detroit.
AB  - The G and P genotypes of rotavirus stool isolates from 100 children were
      determined by reverse transcription-PCR and nucleotide sequencing. G1P[4] was the
      most prevalent genotype(41%), followed by G1P[8] (16%) and G4P[4] (14%). The G
      genoypes detected were G1 (73%), G4 (17.4%), G9 (6.3%), and G2 (2.8%). The P
      genotypes were P[4] (71%) and P[8] (29%). Coinfection with more than one G
      genotype occurred in 12 patients, and coinfection with more than one P genotype
      occurred in 11 patients.

PMID- 12791902
TI  - Epitope-blocking enzyme-linked immunosorbent assays for detection of west nile
      virus antibodies in domestic mammals.
AB  - We evaluated the ability of epitope-blocking enzyme-linked immunosorbent assays
      (ELISAs) to detect West Nile virus (WNV) antibodies in domestic mammals. Sera
      were collected from experimentally infected horses, cats, and pigs at regular
      intervals and screened in ELISAs and plaque reduction neutralization tests. The
      diagnostic efficacies of these techniques were similar.

PMID- 12791904
TI  - Evaluation of the epidemiologic utility of secondary typing methods for
      differentiation of Mycobacterium tuberculosis isolates.
AB  - Spoligotyping and mycobacterial interspersed repetitive unit-variable-number
      tandem repeat analysis (MIRU-VNTR) were evaluated for the ability to
      differentiate 64 Mycobacterium tuberculosis isolates from 10 IS6110-defined
      clusters. MIRU-VNTR performed slightly better than spoligotyping in reducing the
      number of clustered isolates and the sizes of the clusters. All epidemiologically
      related isolates remained clustered by MIRU-VNTR but not by spoligotyping.

PMID- 12791905
TI  - Evaluation of Copan swabs with liquid transport media for use in the Gen-Probe
      Group A Strep Direct Test.
AB  - The Gen-Probe Group A Streptococcus Direct Test (GASDT), which detects the
      presence or absence of group A streptococci directly from pharyngeal specimens,
      utilizes a specific relative light unit (RLU) cutoff of 4,500 to differentiate
      between positive and negative test results. In response to a report by a
      manufacturer that the background RLU values for the Copan rayon swabs with liquid
      media were higher than the RLU values typically observed with Culturette swabs,
      we tested multiple lots of Copan rayon swabs with liquid media and determined
      that the swabs are unacceptable for routine use in the GASDT. The high background
      RLU values for the Copan rayon swabs appear to be a direct result of the gamma
      irradiation used to sterilize the swabs. We also performed a comparative clinical
      evaluation of Copan Dacron swabs with liquid media and Culturette swabs for use
      in the GASDT. Overall, there was 97.5% agreement between the results obtained
      with the Copan Dacron swabs and those obtained with the Culturette swabs.
      Compared to Culturette swabs, the Copan Dacron swabs had a sensitivity and a
      specificity of 97 and 98%, respectively. Copan Dacron swabs with liquid media are
      an acceptable alternative to the swabs currently qualified for use with the
      GASDT, but Copan rayon swabs with liquid transport media should not be used in
      the GASDT.

PMID- 12791907
TI  - Stability of repetitive-sequence PCR patterns with respect to culture age and
      subculture frequency.
AB  - To examine the stability of repetitive-sequence (rep) PCR profiles, six species
      of bacteria were subcultured to blood agar plates and DNA was extracted from the
      cultures after 24, 48, and 72 h of incubation at 35 degrees C. In addition, the
      same species were subcultured to fresh blood plates daily and DNA was extracted
      from the cultures after growth of 5, 10, and 15 subcultures, respectively. rep
      PCR analysis demonstrated that all rep PCR fingerprints from a single species
      were identical.

PMID- 12791906
TI  - Molecular characterization of isolates of waterborne Cryptosporidium spp.
      collected during an outbreak of gastroenteritis in South Burgundy, France.
AB  - In September 2001, a waterborne outbreak of gastroenteritis occurred in eastern
      France. Of 31 fecal samples from symptomatic individuals, 19 tested positive for
      Cryptosporidium with two PCRs targeting the Hsp70 and the 18S rRNA genes of
      CRYPTOSPORIDIUM: Sequencing of the PCR fragments produced sequences identical to
      that of Cryptosporidium parvum genotype 1.

PMID- 12791908
TI  - Identification of Neisseria meningitidis serogroups Y and W135 by siaD nucleotide
      sequence analysis.
AB  - Rapid serogrouping of meningococci is essential for the effective public health
      management of cases of the disease and the contacts of infected patients. Here we
      describe an accurate nucleotide-sequencing method for the confirmation of
      serogroup Y and W135 meningococci by siaD gene analysis from cultures of
      Neisseria meningitidis.

PMID- 12791909
TI  - Predominance of Chlamydia trachomatis serovars associated with urogenital
      infections in females in New Delhi, India.
AB  - Screening for Chlamydia trachomatis was done for 280 endocervical swab samples by
      PCR specific for endogenous plasmid. Age dependency was seen in symptomatic
      patients, with a high chlamydial prevalence rate (28%) found in younger women.
      Genotyping by restriction fragment length polymorphism analysis of omp1 PCR
      positive samples showed serovars D, E, and F to be the most prevalent.

PMID- 12791910
TI  - Comparison of microscan broth microdilution, synergy quad plate agar dilution,
      and disk diffusion screening methods for detection of high-level aminoglycoside
      resistance in enterococcus species.
AB  - We compared the dried MicroScan microdilution panel, Synergy Quad plate agar
      dilution, and high-potency disk diffusion screening methods for the detection of
      high-level aminoglycoside resistance in 815 enterococcal bloodstream isolates.
      Agreement between the three methods was 99% when testing for high-level
      gentamicin resistance and 96% when testing for high-level streptomycin
      resistance.

PMID- 12791911
TI  - Molecular and conventional epidemiology of tuberculosis in Hong Kong: a
      population-based prospective study.
AB  - A prospective population-based molecular and conventional epidemiological study
      of 65.4% of bacteriologically confirmed cases of tuberculosis was carried out on
      the island of Hong Kong from May 1999 to Oct 2000 by the IS6110-based restriction
      fragment length polymorphism technique. Eleven of the isolates had five or fewer
      bands; 24.5% of the remaining 691 isolates belonged to clusters. The estimated
      proportion of recently transmitted disease was 15 to 20%.

PMID- 12791912
TI  - Detection of Pneumocystis carinii and characterization of mutations associated
      with sulfa resistance in bronchoalveolar lavage samples from human
      immunodeficiency virus-infected subjects.
AB  - One hundred ninety-four bronchoalveolar specimens were evaluated by microscopic
      examination and by amplification of a sequence of a Pneumocystis carinii
      dihidropteroate synthase gene for identification of mutations linked to sulfa
      resistance. PCR sensitivity and specificity were 100 and 86.7%, respectively,
      compared to results of microscopic examination. However, 7 out of 19 microscopy
      negative, PCR-positive samples were collected from subjects with a clinically
      high probability of P. carinii pneumonia, suggesting that PCR may be more
      sensitive than microscopic examination, although the absolute performance of PCR
      cannot be determined. Mutations were identified in 28 out of 70 (40%) PCR
      positive specimens and were significantly more common in patients exposed to
      sulfa drugs (21 out of 29 [72.4%]) than in those not exposed to sulfa drugs (4
      out of 35 [11.4%]).

PMID- 12791913
TI  - Interruption of nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy for
      2 months has no effect on levels of human immunodeficiency virus type 1 in plasma
      of patients harboring viruses with mutations associated with resistance to
      NNRTIs.
AB  - A 2-month interruption of only nonnucleoside reverse transcriptase inhibitors
      (NNRTIs) for patients carrying mutations associated with resistance to NNRTIs was
      followed by no change in either viral load or CD4 cell counts. These data suggest
      that these compounds have lost all of their in vivo antiviral activity in such
      cases.

PMID- 12791914
TI  - Bovine non-O157 Shiga toxin 2-containing Escherichia coli isolates commonly
      possess stx2-EDL933 and/or stx2vhb subtypes.
AB  - stx(2) genes from 138 Shiga toxin-producing Escherichia coli (STEC) isolates, of
      which 127 were of bovine origin (58 serotypes) and 11 of human origin (one
      serotype; O113:H21), were subtyped. The bovine STEC isolates from Australian
      cattle carried ehxA and/or eaeA and predominantly possessed stx(2-EDL933) (103 of
      127; 81.1%) either in combination with stx(2vhb) (32 of 127; 25.2%) or on its own
      (52 of 127; 40.4%). Of 22 (90.9%) bovine isolates of serotype O113:H21, a
      serotype increasingly recovered from patients with hemolytic uremic syndrome
      (HUS) or hemorrhagic colitis, 20 contained both stx(2-EDL933) and stx(2vhb); 2
      isolates contained stx(2vhb) only. Although 7 of 11 (63.6%) human O113:H21
      isolates associated with diarrhea possessed stx(2-EDL933), the remaining 4
      isolates possessed a combination of stx(2-EDL933) and stx(2vhb). Three of the
      four were from separate sporadic cases of HUS, and one was from an unknown
      source.

PMID- 12791915
TI  - Characterization of the Manila family of Mycobacterium tuberculosis.
AB  - Forty-eight Mycobacterium tuberculosis strains were obtained from patients living
      in metropolitan Manila, Republic of the Philippines. Three molecular typing
      methods, IS6110 restriction fragment length polymorphism, spoligotyping, and DNA
      sequencing of the oxyR, gyrA, and katG loci, established that these strains have
      restricted diversity and are members of a related genetic group of organisms.
      Comparison of the DNA fingerprint patterns with those in international databases
      confirmed the uniqueness of this group of isolates, which we designate the Manila
      family of M. tuberculosis.

PMID- 12791916
TI  - In vitro detection of dissimilar amounts of hepatitis C virus (HCV) subtype
      specific RNA genomes in mixes prepared from sera of persons infected with a
      single HCV genotype.
AB  - The level of in vitro detection of viral genomes in mixes with two different
      hepatitis C virus (HCV) subtypes was investigated by artificially mixing
      previously measured subtype-specific HCV RNA genomes. The RNAs in these mixtures
      were reverse transcribed and then PCR amplified by using two sets of primers
      corresponding to the 5' untranslated region and digested with endonucleases to
      analyze the restriction fragment length polymorphism patterns. This approach
      facilitated detection of a wider range of type-specific HCV genomes than
      originally described, beyond equimolar concentrations of contributing HCV
      subtypes. Moreover, by using computerized image analysis, this study also
      demonstrated that the true contribution of each virus type-and consequently of
      mixed infections-may be underestimated when only visual observation is carried
      out. These results may be useful for comparing data obtained from this and other
      currently used methodologies.

PMID- 12791917
TI  - Detection of Chlamydophila felis and feline herpesvirus by multiplex real-time
      PCR analysis.
AB  - Chlamydophila felis and feline herpesvirus (FHV) are pathogens commonly
      associated with feline respiratory and ocular disease. A real-time multiplex PCR
      assay was developed to allow detection of these organisms, together with feline
      28S ribosomal DNA, in a single tube. Of 538 ocular swab samples tested, 123 were
      positive for FHV, 97 were positive for C. felis, and 16 were positive for both
      pathogens.

PMID- 12791918
TI  - Genetic diversity of Gallibacterium anatis isolates from different chicken
      flocks.
AB  - Amplified fragment length polymorphisms (AFLPs) were used to characterize the
      genotypic diversity of a total of 114 Gallibacterium anatis isolates originating
      from a reference collection representing 15 biovars from four countries and
      isolates obtained from tracheal and cloacal swab samples of chickens from an
      organic, egg-producing flock and a layer parent flock. A subset of strains was
      also characterized by pulsed-field gel electrophoresis and biotyping. The organic
      flock isolates were characterized by more than 94% genetic similarity, indicating
      that only a single clone was apparent in the flock. The layer parent flock
      isolates were grouped into two subclusters, each with similarity above 90%. One
      subcluster contained only tracheal isolates, while the other primarily included
      cloacal isolates. In conclusion, we show that AFLP analysis enables
      fingerprinting of G. anatis, which seems to have a clonal population structure
      within natural populations. There was further evidence of clonal lineages, which
      may have adapted to different sites within the same animal.

PMID- 12791919
TI  - Interpreting the results of the amplified Mycobacterium tuberculosis direct test
      for detection of M. tuberculosis rRNA.
AB  - The Amplified Mycobacterium tuberculosis Direct (AMTD) test detects M.
      tuberculosis rRNA. By using culture of M. tuberculosis as a gold standard, a
      number of different diagnostic indices were examined in an attempt to determine
      the diagnostic performance of the AMTD test and demonstrate how it might usefully
      be interpreted during the early management of disease.

PMID- 12791920
TI  - Subgenotype analysis of Cryptosporidium isolates from humans, cattle, and zoo
      ruminants in Portugal.
AB  - Cryptosporidium parvum and Cryptosporidium hominis isolates from human
      immunodeficiency virus-infected patients, cattle, and wild ruminants were
      characterized by PCR and DNA sequencing analysis of the 60-kDa glycoprotein gene.
      Seven alleles were identified, three corresponding to C. hominis and four
      corresponding to C. parvum. One new allele was found (IId), and one (IIb) had
      only been found in Portugal. Isolates from cattle and wild ruminants clustered in
      two alleles. In contrast, human isolates clustered in seven alleles, showing
      extensive allelic diversity.

PMID- 12791921
TI  - Sequence analysis of the matrix (M2) protein gene of avian pneumovirus recovered
      from turkey flocks in the United States.
AB  - We here report the comparative sequence and phylogenetic analysis of the avian
      pneumovirus subgroup C (APV C) matrix (M2) gene of cell culture-adapted isolates
      and clinical samples. Limited heterogeneity was observed among the M2 sequences,
      suggesting that diagnostic tests and vaccines against APV C are likely to exhibit
      broad cross-reactivity.

PMID- 12791922
TI  - Desulfovibrio desulfuricans bacteremia and review of human Desulfovibrio
      infections.
AB  - One case of primary Desulfovibrio desulfuricans bacteremia in an immunocompetent
      man is presented, and 15 other reported cases are reviewed. While most isolates
      have not been identified to the species level, Desulfovibrio fairfieldensis and
      D. desulfuricans have been associated with incidents of bacteremia and D.
      vulgaris has been associated with intra-abdominal infections. In vitro studies
      suggest that empirical therapy with either imipenem or metronidazole should be
      considered.

PMID- 12791923
TI  - Microbiologic surveillance using nasal cultures alone is sufficient for detection
      of methicillin-resistant Staphylococcus aureus isolates in neonates.
AB  - During an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the
      neonatal intensive care units at two hospitals, we assessed several sites for
      detection of MRSA colonization. Nasal cultures found 32 of 33 MRSA-colonized
      patients (97%). Rectal cultures detected 29% of 24 MRSA-colonized patients
      identified by paired rectal and nasal samples and axillary samples found 22% of 9
      MRSA-colonized patients identified by axillary samples paired with nasal swabs.
      There were no positive umbilical samples.

PMID- 12791924
TI  - Plasma versus serum for detection of herpes simplex virus type 2-specific
      immunoglobulin G antibodies with a glycoprotein G2-based enzyme immunoassay.
AB  - To evaluate the consonance between plasma and serum for the detection of herpes
      simplex virus type 2-specific immunoglobulin G antibodies, we compared results
      from concurrently obtained plasma and sera in 710 sexually active women by using
      a glycoprotein G2-based enzyme-linked immunosorbent assay (Focus Technologies,
      Cypress, Calif.) and found 98.9% agreement between the two specimen types. Plasma
      appears to be an acceptable matrix for use with this assay.

PMID- 12791925
TI  - Emergence of novel human group A rotavirus G12 strains in India.
AB  - Three rare human G12 strains were detected from diarrheic clinical samples of
      children (<8 months of age) in Calcutta during a routine surveillance study of
      rotaviral diarrhea in India. The VP7 genes of G12 strains and their products
      showed maximum homology (97 to 99% at the nucleotide level and 98% at the amino
      acid level, respectively) with those of two recently reported G12 strains (from
      the United States and Thailand) but lesser homology with those of prototype G12
      strain L26.

PMID- 12791926
TI  - Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive
      women with high-grade cervical lesions are strongly elevated.
AB  - Human papillomavirus (HPV) DNA loads of six oncogenic HPV types were measured by
      real-time PCR in cervical scrapes of human immunodeficiency virus (HIV)-infected
      and uninfected women. In both groups, HPV loads increased with the grade of
      cervical disease. HIV infection did not affect HPV loads in low-grade lesions but
      was associated with significantly higher HPV loads in severe dysplasia; highest
      loads were found in advanced HIV disease. Our data reflect the aggressive course
      of HPV infection in HIV-positive women.

PMID- 12791927
TI  - Nocardia veterana isolated from ascitic fluid of a patient with human
      immunodeficiency virus infection.
AB  - Nocardia veterana is a recently characterized species within the genus Nocardia,
      and only three human clinical isolates have been reported for this species. We
      describe a case of ascitic fluid infection in an immunocompromised patient due to
      N. veterana. To our knowledge, this is the first report of a Nocardia sp. strain
      from ascitic fluid and the fourth report of N. veterana isolated from human
      samples. Chemotaxonomic methods showed the strain to belong to the genus
      Nocardia, and identification to the species level was done by 16S ribosomal DNA
      gene sequencing. The antibiotic susceptibility profile of N. veterana is reported
      here for the second time. The strain was deposited in the Collection of the
      Pasteur Institute and in the Culture Collection of the University of Goteborg
      (CIP 107497 and CCUG 46576). The corresponding 16S ribosomal DNA gene sequence is
      available from the GenBank database under accession number AY149599. A
      phylogenetic analysis was conducted and showed that N. veterana was most closely
      related to the recently characterized species Nocardia africana rather than to
      Nocardia vaccinii, as previously reported.

PMID- 12791928
TI  - Francisella tularensis bacteremia.
AB  - Bacteremia caused by Francisella tularensis is rare and has been reported mainly
      in the United States and infrequently in Europe. We report herein the first case
      of bacteremic F. tularensis pneumonia in an immunocompetent individual in
      southern Europe.

PMID- 12791929
TI  - Corynebacterium freneyi bacteremia.
AB  - Corynebacterium freneyi is a recently described alpha-glucosidase-positive
      species of the genus CORYNEBACTERIUM: To our knowledge, there is no description
      of human infection due to this species. We report on a case of bacteremia due to
      C. freneyi following vascular surgery.

PMID- 12791930
TI  - Soft tissue infection caused by a novel pigmented, rapidly growing mycobacterium
      species.
AB  - Molecular techniques are playing an important role in the diagnosis of
      nontuberculous mycobacterial infections. This case report describes a chronic
      soft tissue infection in an immunocompetent patient caused by a previously
      undescribed pigmented, rapidly growing Mycobacterium species, emphasizing the
      importance of clinical suspicion and effective laboratory techniques in the
      diagnosis and treatment of infection.

PMID- 12791931
TI  - Lactobacillus paracasei continuous ambulatory peritoneal dialysis-related
      peritonitis and review of the literature.
AB  - We describe the first case of continuous ambulatory peritoneal dialysis (CAPD)
      related peritonitis due to Lactobacillus paracasei. It occurred in a 65-year-old
      patient with recurrent episodes of peritonitis while he was receiving a prolonged
      course of intraperitoneal vancomycin. L. paracasei should be considered in the
      differential diagnosis of pathogens in CAPD-related peritonitis, especially in
      patients receiving prolonged vancomycin or glycopeptide treatment.

PMID- 12791932
TI  - Disseminated infection with a mycobacterium related to Mycobacterium triplex with
      central nervous system involvement associated with AIDS.
AB  - We report on a case of disseminated infection with central nervous system
      involvement due to an atypical mycobacterium related to Mycobacterium triplex in
      a severely immunodepressed human immunodeficiency virus-infected man.

PMID- 12791934
TI  - Improving the specificity of recombinant immunoassays for lyme disease.

PMID- 12791933
TI  - Tuboovarian abscess caused by Atopobium vaginae following transvaginal oocyte
      recovery.
AB  - A 39-year-old woman with tubarian sterility fell ill with acute pelvic
      inflammatory disease 2 months after transvaginal oocyte recovery. Laparotomy
      revealed a large tuboovarian abscess, from which Atopobium vaginae, an anaerobic
      gram-positive coccoid bacterium of hitherto unknown clinical significance, was
      isolated. The microbial etiology and the risk of pelvic infections following
      transvaginal punctures are discussed.

PMID- 12791935
TI  - Algorithm specification interface for human immunodeficiency virus type 1
      genotypic interpretation.

PMID- 12791936
TI  - Initial quality control evaluations for susceptibility testing of Dalbavancin
      (BI397), an investigational glycopeptide with potent gram-positive activity.

PMID- 12791937
TI  - Updated version of the Burkholderia cepacia complex experimental strain panel.

PMID- 12791938
TI  - Stroke associated with sympathomimetics contained in over-the-counter cough and
      cold drugs.
AB  - BACKGROUND AND PURPOSE: Phenylpropanolamine (PPA) and pseudoephedrine are
      sympathomimetics contained in over-the-counter cold preparations. A case-control
      study linked PPA use with hemorrhagic stroke in women. Twenty-two patients with
      stroke associated with use of these drugs are described. METHODS: In a
      consecutive stroke registry since 1988, 22 patients had stroke associated with
      over-the-counter sympathomimetics. Sympathomimetic dosage and type, time interval
      until stroke onset, and neuroimaging findings are described. RESULTS: Ten male
      and 12 female patients were included. Intracerebral hemorrhage occurred in 17
      patients, subarachnoid hemorrhage in 4, and ischemic stroke in 1. Stroke was
      associated with PPA use in 16 patients (dose 75 to 675 mg), with pseudoephedrine
      in 4 (dose 60 to 300 mg), and with others administered by the nasal route in 2
      (oxymetazoline and phenylephrine). Stroke occurred after a single dose in 17
      patients and after daily use during several days in 5. The interval between drug
      exposure and clinical onset varied from 30 minutes to 24 hours. Stroke occurred
      after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg)
      in 50% of patients. Eight patients had acute hypertension at stroke onset.
      Cerebral angiography was normal in 8 cases and showed diffuse vasospasm or
      beading in 10 patients. CONCLUSIONS: Stroke related to over-the-counter
      sympathomimetics was associated with acute hypertension and/or vasospasm or
      angiitis mechanisms, most related to the use of PPA; however, stroke also
      occurred with the use of other sympathomimetics, particularly pseudoephedrine.
      Although stroke complications occurred when doses were used that were higher than
      recommended doses, apparently there is also a stroke risk when these agents are
      taken properly.

PMID- 12791939
TI  - Polymorphism in the promoter region of the insulin-like growth factor I gene is
      related to carotid intima-media thickness and aortic pulse wave velocity in
      subjects with hypertension.
AB  - BACKGROUND AND PURPOSE: Low circulating levels of insulin-like growth factor I
      (IGF-I) have been associated with an increased risk for atherosclerosis. Absence
      of the 192-bp (wild-type) allele in the promoter region of the IGF-I gene has
      been associated with low circulating IGF-I levels. We examined the role of this
      polymorphism in relation to blood pressure and 2 early markers of
      atherosclerosis: carotid intima-media thickness (IMT) and aortic pulse wave
      velocity (PWV). METHODS: A total of 5132 subjects of the Rotterdam Study, aged 55
      to 75 years, were included in this study. In 3769 subjects who did not use blood
      pressure-lowering medication, the association between the IGF-I polymorphism and
      blood pressure was examined. In the total population, and in 3484 normotensive
      subjects, 1648 hypertensive and 462 untreated hypertensive subjects, the
      association between this polymorphism and IMT and PWV was examined. RESULTS: Mean
      systolic and diastolic blood pressure did not differ between genotypes. In
      hypertensive subjects IMT was significantly increased in noncarriers of the 192
      bp allele (0.83 mm) compared with heterozygous or homozygous carriers (0.80 mm)
      (P=0.04). PWV was also significantly higher in hypertensive subjects who were
      noncarriers of the 192-bp allele (14.3 m/s) compared with heterozygous (14.1 m/s)
      or homozygous carriers (13.7 m/s) (P=0.02). Findings were more pronounced in
      hypertensive subjects without medication use. In normotensive subjects, no
      association between this polymorphism, IMT, and PWV was observed. CONCLUSIONS:
      Our study suggests that hypertensive subjects who have low IGF-I levels because
      of a genetic polymorphism in the IGF-I gene are at increased risk of developing
      atherosclerosis.

PMID- 12791940
TI  - Cerebral hemodynamic evaluation using perfusion-weighted magnetic resonance
      imaging: comparison with positron emission tomography values in chronic occlusive
      carotid disease.
AB  - BACKGROUND AND PURPOSE: Perfusion-weighted magnetic resonance imaging (PWI) is a
      reliable and semiquantitative method for estimating cerebral hemodynamics. We
      sought to evaluate the potential of PWI for assessing cerebral blood flow (CBF)
      and metabolism compared with positron emission tomography (PET) in patients with
      chronic occlusive carotid disease. METHODS: In 24 patients with chronic
      unilateral occlusive carotid disease, time-to-peak (TTP) delay (TTP-D) measured
      by PWI was compared with CBF, cerebral blood volume (CBV), and oxygen extraction
      fraction (OEF) obtained by PET. TTP indicates the time from the start of PWI to
      the bolus peak. TTP-D indicates the difference in TTP values between the
      occlusive and contralateral hemispheres. TTP-D was compared between patients with
      normal and reduced CBF/CBV and also between patients with normal and elevated
      OEF. RESULTS: TTP-D in patients with reduced CBF/CBV was significantly longer
      than that in patients with normal CBF/CBV (3.4+/-1.8 versus 1.4+/-0.7 seconds;
      P<0.001). In the patients with reduced CBF/CBV, TTP-D correlated with OEF
      significantly (r=0.710, P<0.0001). TTP-D in patients with elevated OEF was
      significantly longer than that in patients with normal OEF (4.8+/-2.2 versus
      2.0+/-0.9 seconds; P<0.01). In all 5 patients with TTP-D >or=4 seconds, OEF was
      elevated markedly. CONCLUSIONS: TTP-D >or=4 seconds is considered to indicate a
      high risk of hemodynamic failure. The measurement of TTP-D by PWI appears to
      provide important clinical information for evaluating cerebral hemodynamics in
      chronic occlusive carotid disease.

PMID- 12791941
TI  - Mitochondrial ATP-sensitive potassium channel activation protects cerebellar
      granule neurons from apoptosis induced by oxidative stress.
AB  - BACKGROUND AND PURPOSE: Mitochondrial ATP-sensitive potassium (mitoK(ATP))
      channels are present in the brain, and several reports have shown that mitoK(ATP)
      channel openers protect the brain against ischemic injury. However, the precise
      mechanisms of this protection are not well established. We hypothesized that
      mitoK(ATP) channel openers prevent apoptosis by preserving mitochondrial membrane
      potential. METHODS: We investigated the effect of mitoK(ATP) channel openers on
      apoptosis induced by oxidative stress using cultured cerebellar granule neurons.
      RESULTS: The mitoK(ATP) channel opener diazoxide (100 micromol/L) significantly
      suppressed the number of cells with terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL)-positive nuclei and the increase in
      caspase-3 activity induced by 20 micromol/L H2O2. Diazoxide and another opener,
      pinacidil, prevented the loss of mitochondrial inner membrane potential
      (Delta(Psi)m) induced by H2O2. These effects were abolished by 5-hydroxydecanoate
      (500 micromol/L), a mitoK(ATP) channel blocker. Cyclosporin A and bongkrekic
      acid, inhibitors of the mitochondrial permeability transition pore, also
      prevented Delta(Psi)m loss, confirming the involvement of the mitochondrial
      permeability transition in the apoptotic cascade in neurons. Furthermore,
      diazoxide prevented the increase in extracellular glutamate concentration induced
      by H2O2, but this effect was not attributable to activation of surface K(ATP)
      channels. CONCLUSIONS: MitoK(ATP) channel openers inhibited apoptosis by
      preserving mitochondrial inner membrane potential. These beneficial effects may
      suggest a possible new target for neuroprotection.

PMID- 12791942
TI  - Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal
      forebrain ischemia in C57Black/Crj6 mouse striatum.
AB  - BACKGROUND AND PURPOSE: Ischemic injury in neurons can be strongly reduced by a
      preceding sublethal ischemic episode, of which the mechanism is poorly
      understood. Although changes in the expression of apoptosis-related proteins (Bcl
      2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic
      injury, the roles these proteins play in ischemic preconditioning induced by
      sublethal forebrain ischemia have not been elucidated. Therefore, we investigated
      the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice
      subjected to sublethal forebrain ischemia and lethal ischemia, with or without
      ischemic preconditioning. METHODS: Sublethal forebrain ischemia was induced in
      C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery
      occlusion. The transcription and expression of Bcl-2 family genes were detected
      by reverse transcription-polymerase chain reaction, Western blot, and
      immunofluorescent staining. RESULTS: No detectable neuronal loss was induced in
      striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription
      and expression of Bcl-2 and Bcl-xl were increased after sublethal forebrain
      ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The
      transcription and expression of Bax remained unchanged. CONCLUSIONS: Upregulation
      of Bcl-2 and Bcl-xl but not Bax may have a role in protective ischemic
      preconditioning. This result indicates a potential strategy for further ischemic
      neuronal injury therapies.

PMID- 12791945
TI  - Adoptive transfer of myelin basic protein-tolerized splenocytes to naive animals
      reduces infarct size: a role for lymphocytes in ischemic brain injury?
AB  - BACKGROUND AND PURPOSE: Breakdown of the blood-brain barrier during stroke allows
      central nervous system antigens to leak into the systemic circulation and allows
      circulating leukocytes access to the brain. Encounter of central nervous system
      antigens by the peripheral immune system can be capitalized on to modulate the
      postischemic inflammatory response and potentially improve outcome from stroke.
      METHODS: Male Lewis rats were tolerized to myelin basic protein (MBP) or
      ovalbumin (OVA) and subjected to 3 hours of middle cerebral artery occlusion
      (MCAO) or used as splenocyte donors for immunologically naive animals undergoing
      MCAO. Infarct size was determined at 24 hours by 2,3,5-triphenyltetrazolium
      chloride staining. In separate studies, mononuclear cells were removed from the
      brains of animals after MCAO for enzyme-linked immunospot (ELISPOT) assay and
      flow cytometry. RESULTS: Median infarct volume in animals tolerized to MBP and
      those receiving splenocytes from MBP-tolerized donors was less than in animals
      tolerized to OVA and those receiving splenocytes from OVA-tolerized donors
      (87.7+/-54.9 versus 148+/-61.6 mm3 [P=0.01] and 89.2+/-77.5 versus 153+/-77.1 mm3
      [P=0.05], respectively). There was an increase in the number of transforming
      growth factor-beta1-secreting mononuclear cells in MBP-tolerized animals
      undergoing sham surgery (P=0.001) as well as in ischemic animals 48 hours
      (P=0.02) and 336 hours (P=0.04) after stroke. A distinct subset of gammadelta T
      cells was present in the brains of MBP-tolerized but not control animals after
      stroke. CONCLUSIONS: Immunologic tolerance and its neuroprotective effects can be
      transferred to naive animals and appear to be related to antigen-specific
      induction of transforming growth factor-beta1.

PMID- 12791944
TI  - Dynamic pressure--flow velocity relationships in the human cerebral circulation.
AB  - BACKGROUND AND PURPOSE: The pressure-flow velocity relationship in the cerebral
      circulation is characterized by the critical closing pressure (CCP), which is the
      pressure at which flow ceases, and the linear slope of a plot between pressure
      and flow velocity. It has been suggested, but not validated, that CCP can be
      determined from arterial blood pressure (ABP) and transcranial Doppler (TCD)
      recordings during the cardiac cycle. We studied a group of patients in whom
      ventricular fibrillation (VF) was induced. The time interval before
      defibrillation enabled calculation of CCP from data in which flow approached
      zero. These estimates were compared with values calculated before and after
      fibrillation and during regular heartbeats. METHODS: TCD velocities and ABP in
      the radial artery were recorded before, during, and after 28 episodes of VF in 13
      patients. CCPs were calculated by 3 different methods: (1) linear extrapolation
      from data during VF (gold standard); (2) linear extrapolation from normal
      heartbeat data; and (3) first harmonic Fourier filtering of normal heartbeat
      data. RESULTS: The CCP during VF calculated from long diastoles was 32.9+/-11 mm
      Hg (mean+/-SD). The regular heartbeat estimate was 6.0+/-4.3 mm Hg lower
      (P<0.05). The CCP estimate with the use of a Fourier filter was 1.4+/-3.9 mm Hg
      (P=NS) lower than during VF. During hyperemia after defibrillation, the CCP
      decreased by 13.3 mm Hg, while velocity increased by 63%. The decrease in CCP
      could explain half of the increase in flow velocity during hyperemia.
      CONCLUSIONS: CCP can be accurately estimated from regular heartbeat data and is
      an important factor in regulation of the cerebral circulation.

PMID- 12791943
TI  - Rapid perfusion abnormality estimation in acute stroke with temporal correlation
      analysis.
AB  - BACKGROUND AND PURPOSE: Determination of the presence or absence of ischemic
      penumbra through diffusion-perfusion mismatch requires rapid delineation of both
      abnormalities. Although singular value decomposition-based perfusion parameter
      estimation has offered valuable insights into the underlying cerebral
      hemodynamics, the associated postprocessing procedures have limited its
      widespread use. We explored the utility of a simple technique to define perfusion
      abnormality in acute stroke patients. METHODS: Twenty acute stroke patients were
      studied. The MR dynamic contrast approach was used to obtain cerebral blood flow,
      cerebral blood volume, and mean transit time (MTT). Temporal correlation was used
      to correlate 4 reference functions-an arterial input function (AIF), a normal
      tissue function, a lesion function, and a venous output function-with dynamic
      contrast MR images, and correlation coefficients (CCs) were calculated pixel by
      pixel. In addition, chronic-state T2-weighted images were coregistered onto the
      images acquired acutely for assessing the sensitivity and specificity of CC
      defined lesion. RESULTS: Statistically significant differences in cerebral blood
      flow and MTT were found between CC-defined normal and abnormal tissues with all 4
      reference functions used. When the final infarct volume was used as the gold
      standard, a similar sensitivity between MTT (78%) and AIF (76%) CC-defined lesion
      was obtained, whereas the specificity was higher for AIF (61%) than that obtained
      with MTT-defined lesion (52%). CONCLUSIONS: We explored CC maps as a simpler
      alternative of estimating perfusion abnormality, and results demonstrated the
      potential clinical utility of a correlation-based technique for estimating brain
      perfusion status.

PMID- 12791947
TI  - Happy birthday, Science international.

PMID- 12791948
TI  - Marine research. Pew panel calls for sea change in U.S. ocean policy.

PMID- 12791949
TI  - Human genome. A low number wins the GeneSweep Pool.

PMID- 12791946
TI  - Pentanucleotide TTTTA repeat polymorphism of apolipoprotein(a) gene and plasma
      lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a
      multicenter case-control study in China.
AB  - BACKGROUND AND PURPOSE: It is still inconclusive whether high plasma
      lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and
      different ethnic groups and methodologies might be contributors to the conflicts
      in study results. The purpose of the present study was to investigate the
      association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR)
      polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case
      control study. METHODS: We recruited 1825 cases with stroke (44.3% cerebral
      atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage)
      and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified
      by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene
      was determined by polymerase chain reaction-polyacrylamide gel electrophoresis.
      Conditional multivariate logistic regression analysis was used to identify
      independent risk factors for stroke and its subtypes. RESULTS: Lp(a) levels were
      significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL;
      P<0.001), leading to a 1.97-fold (95% CI, 1.64 to 2.37) increase in risk for
      overall stroke, 2.0-fold (95% CI, 1.59 to 2.52) increase for atherothrombotic
      type, 2.05-fold increase (95% CI, 1.59 to 2.63) for lacunar type, and 1.64-fold
      increase (95% CI, 1.21 to 2.21) for hemorrhagic type. The number of PNTR
      negatively correlated with Lp(a) levels. Low-number repeats (sum of both alleles
      <16) of apo(a) PNTR were associated with both atherothrombotic stroke (odds
      ratio, 1.41; 95% CI, 1.04 to 1.91) and hemorrhagic stroke (odds ratio, 1.62; 95%
      CI, 1.09 to 2.37). CONCLUSIONS: Our results indicate for the first time that low
      numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with
      both ischemic and hemorrhagic stroke in Chinese.

PMID- 12791950
TI  - Genomic medicine. African-American population biobank proposed.

PMID- 12791951
TI  - Marine research. Congress fiddles with law while scientists burn.

PMID- 12791952
TI  - Underground science. Flooding mine could doom Homestake plan.

PMID- 12791953
TI  - Infectious diseases. Searching for a SARS agenda.

PMID- 12791954
TI  - Postwar Iraq. Assyrian gold safe as looters threaten southern sites.

PMID- 12791955
TI  - Theoretical physics. Calculations pop the cork on travel through spacetime
      tunnels.

PMID- 12791956
TI  - After the war. Iraq's shattered universities.

PMID- 12791958
TI  - Planetary science. Running water eroded a frigid early Mars.

PMID- 12791957
TI  - Heart disease. How to subdue a swelling heart.

PMID- 12791959
TI  - American Astronomical Society meeting. Hubble prepares to go really deep.

PMID- 12791961
TI  - American Astronomical Society meeting. Gamma ray bursts get magnetic.

PMID- 12791960
TI  - American Astronomical Society meeting. When do planets form? Inquiring
      astronomers want to know.

PMID- 12791962
TI  - American Astronomical Society meeting. Snapshots from the meeting.

PMID- 12791963
TI  - Smallpox bioterror response.

PMID- 12791964
TI  - MDMA ("ecstasy") and neurotoxicity.

PMID- 12791965
TI  - Research fraud, public policy, and gun control.

PMID- 12791966
TI  - Comment on "Climate and management contributions to recent trends in U.S.
      agricultural yields".

PMID- 12791968
TI  - Essays on science and society. Fighting for Thirlmere--the roots of
      environmentalism.

PMID- 12791970
TI  - Geochemistry. How old is planet Earth?

PMID- 12791969
TI  - Molecular biology. Beginning at the end.

PMID- 12791971
TI  - Plant science. Surprises inside a green grass genome.

PMID- 12791972
TI  - Chemistry. Optical analogs of 2D NMR.

PMID- 12791973
TI  - Molecular biology. A self-help guide for a trim genome.

PMID- 12791974
TI  - Does the trigger for abrupt climate change reside in the ocean or in the
      atmosphere?
AB  - Two hypotheses have been put forward to explain the large and abrupt climate
      changes that punctuated glacial time. One attributes such changes to
      reorganizations of the ocean's thermohaline circulation and the other to changes
      in tropical atmosphere-ocean dynamics. In an attempt to distinguish between these
      hypotheses, two lines of evidence are examined. The first involves the timing of
      the freshwater injections to the northern Atlantic that have been suggested as
      triggers for the global impacts associated with the Younger Dryas and Heinrich
      events. The second has to do with evidence for precursory events associated with
      the Heinrich ice-rafted debris layers in the northern Atlantic and with the
      abrupt Dansgaard-Oeschger warmings recorded in the Santa Barbara Basin.

PMID- 12791976
TI  - Toll-like receptor signaling pathways.
AB  - Members of the Toll-like receptor (TLR) family recognize conserved microbial
      structures, such as bacterial lipopolysaccharide and viral double-stranded RNA,
      and activate signaling pathways that result in immune responses against microbial
      infections. All TLRs activate MyD88-dependent pathways to induce a core set of
      stereotyped responses, such as inflammation. However, individual TLRs can also
      induce immune responses that are tailored to a given microbial infection. Thus,
      these receptors are involved in both innate and adaptive immune responses. The
      mechanisms and components of these varied responses are only partly understood.
      Given the importance of TLRs in host defense, dissection of the pathways they
      activate has become an important emerging research focus. TLRs and their pathways
      are numerous; Science's Signal Transduction Knowledge Environment's TLR
      Connections Map provides an immediate, clear overview of the known components and
      relations of this complex system.

PMID- 12791977
TI  - The signal to move: D. discoideum go orienteering.
AB  - Cells migrating directionally toward a chemoattractant source display a highly
      polarized cytoskeletal organization, with F-actin localized predominantly at the
      anterior and myosin II at the lateral and posterior regions. Dictyostelium
      discoideum has proven a useful system for elucidating signaling pathways that
      regulate this chemotactic response. During development, extracellular adenosine
      3', 5' monophosphate (cAMP) functions as a primary signal to activate cell
      surface cAMP receptors (cARs). These receptors transduce different signals
      depending on whether or not they are coupled to heterotrimeric guanine nucleotide
      binding proteins (G proteins) (see the STKE Connections Maps). Multiple G protein
      stimulated pathways interact to establish polarity in chemotaxing D. discoideum
      cells by localizing F-actin at their leading edge and by regulating the
      phosphorylation state and assembly of myosin II. Many of the molecular
      interactions described are fundamental to the regulation of chemotaxis in other
      eukaryotic cells.

PMID- 12791978
TI  - Interleukin-4 and interleukin-13 signaling connections maps.
AB  - Cytokines are inflammatory mediators important in responding to pathogens and
      other foreign challenges. Interleukin-4 (IL-4) and IL-13 are two cytokines
      produced by T helper type 2 cells, mast cells, and basophils. In addition to
      their physiological roles, these cytokines are also implicated in pathological
      conditions such as asthma and allergy. IL-4 can stimulate two receptors, type I
      and type II, whereas IL-13 signaling is mediated only by the type II receptor
      (see the STKE Connections Maps). These cytokines activate the Janus kinase/signal
      transducer and activator of transcription (JAK/STAT) signaling cascades, which
      may contribute to allergic responses. In addition, stimulation of the
      phosphatidylinositol 3-kinase (PI3K) pathway through recruitment of members of
      the insulin receptor substrate family may contribute to survival and
      proliferation.

PMID- 12791979
TI  - Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions.
AB  - Wnts control the specification of cell fate, cell adhesion, migration, polarity,
      and proliferation. Their roles in development have been probed in fruit flies,
      nematodes, zebrafish, frogs, and mice. Some Wnts inhibit the degradation of beta
      catenin, which can regulate transcription of specific genes. Other Wnts exert
      their influences in other ways, such as increasing intracellular concentrations
      of Ca2+ and decreasing intracellular concentrations of cyclic guanosine
      monophosphate (cGMP). Heterotrimeric guanine nucleotide-binding proteins (G
      proteins) and RGS proteins have been implicated in Wnt signaling. Wnt regulation
      of intracellular Ca2+ and cGMP levels requires the G protein transducin and a
      cGMP-specific phosphodiesterase, which are major elements in signaling of the
      visual pathway.

PMID- 12791980
TI  - Myocyte adrenoceptor signaling pathways.
AB  - Adrenoceptors (ARs), members of the G protein-coupled receptor superfamily, form
      the interface between the sympathetic nervous system and the cardiovascular
      system, with integral roles in the rapid regulation of myocardial function.
      However, in heart failure, chronic catecholamine stimulation of adrenoceptors has
      been linked to pathologic cardiac remodeling, including myocyte apoptosis and
      hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling
      to different G proteins and induction of specific signaling pathways, which is
      partly regulated by the subtype-specific distribution of receptors in plasma
      membrane compartments containing distinct complexes of signaling molecules. The
      Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways
      bring into focus the specific signaling pathways of individual AR subtypes and
      their relevant functions in vivo.

PMID- 12791981
TI  - Regulators of cerebellar granule cell development act through specific signaling
      pathways.
AB  - The proper development of the central nervous system depends upon a finely tuned
      balance between cell proliferation and programmed cell death (PCD). Although PCD
      was initially believed to depend solely on the inability of certain neurons to
      obtain access to a limited supply of trophic factors, it has become apparent that
      the local production of death signals is also critical. In this Viewpoint, we
      discuss several pathways implicated in the survival of cerebellar granule cells-
      both pathways that protect from apoptosis and pathways that promote apoptosis-and
      describe how these disparate pathways converge on the final common mediators of
      PCD. Information on other important pathways implicated in granule cell survival
      may be found in the Connections Maps.

PMID- 12791982
TI  - Circadian rhythms: in the loop at last.
AB  - The basic molecular mechanisms underlying circadian oscillators follow the same
      general plan across the phylogenetic spectrum: oscillating feedback loops in
      which clock gene products negatively regulate their own expression. The circadian
      clocks of animals involve at least two interacting feedback loops. This Viewpoint
      compares and contrasts the circadian clocks of mammals and of Drosophila,
      emphasizing how different players are used to create the same basic script. Both
      the general script and the specific details of the murine and Drosophila
      circadian pathways are available at Science's Signal Transduction Knowledge
      Environment Connections Maps.

PMID- 12791983
TI  - Effects of gaze on amygdala sensitivity to anger and fear faces.

PMID- 12791984
TI  - Photonic devices based on in-plane hetero photonic crystals.

PMID- 12791986
TI  - Dimples on nanocrystalline fracture surfaces as evidence for shear plane
      formation.
AB  - Tensile experiments of fully dense nanocrystalline structures with a mean grain
      size of less than 100 nanometers demonstrate a considerable increase in hardness
      but a remarkable drop in elongation-to-failure, indicating brittle behavior.
      However, dimple structures are often observed at the fracture surface, indicating
      some type of ductile fracture mechanism. Guided by large-scale atomistic
      simulations, we propose that these dimple structures result from local shear
      planes formed around clustered grains that, because of their particular
      misorientation, cannot participate in the grain boundary accommodation processes
      necessary to sustain plastic deformation. This raises the expectation that
      general high-angle grain boundaries are necessary for good ductility.

PMID- 12791988
TI  - Seismic evidence for water deep in Earth's upper mantle.
AB  - Water in the deep upper mantle can influence the properties of seismic
      discontinuities in the mantle transition zone. Observations of converted seismic
      waves provide evidence of a 20- to 35-kilometer-thick discontinuity near a depth
      of 410 kilometers, most likely explained by as much as 700 parts per million of
      water by weight.

PMID- 12791985
TI  - Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
AB  - The function of the ATR (ataxia-telangiectasia mutated- and Rad3-related)-ATRIP
      (ATR-interacting protein) protein kinase complex is crucial for the cellular
      response to replication stress and DNA damage. Here, we show that replication
      protein A (RPA), a protein complex that associates with single-stranded DNA
      (ssDNA), is required for the recruitment of ATR to sites of DNA damage and for
      ATR-mediated Chk1 activation in human cells. In vitro, RPA stimulates the binding
      of ATRIP to ssDNA. The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP
      complex to associate with DNA and stimulates phosphorylation of the Rad17 protein
      that is bound to DNA. Furthermore, Ddc2, the budding yeast homolog of ATRIP, is
      specifically recruited to double-strand DNA breaks in an RPA-dependent manner. A
      checkpoint-deficient mutant of RPA, rfa1-t11, is defective for recruiting Ddc2 to
      ssDNA both in vivo and in vitro. Our data suggest that RPA-coated ssDNA is the
      critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and
      facilitates its recognition of substrates for phosphorylation and the initiation
      of checkpoint signaling.

PMID- 12791987
TI  - Femtosecond phase-coherent two-dimensional spectroscopy.
AB  - Femtosecond phase-coherent two-dimensional (2D) spectroscopy has been
      experimentally demonstrated as the direct optical analog of 2D nuclear magnetic
      resonance. An acousto-optic pulse shaper created a collinear three-pulse sequence
      with well-controlled and variable interpulse delays and phases,which interacted
      with a model atomic system of rubidium vapor. The desired nonlinear polarization
      was selected by phase cycling (coadding experimental results obtained with
      different interpulse phases). This method may enhance our ability to probe the
      femtosecond structural dynamics of macromolecules.

PMID- 12791989
TI  - Laboratory simulation of charge exchange-produced X-ray emission from comets.
AB  - In laboratory experiments using the engineering spare microcalorimeter detector
      from the ASTRO-E satellite mission, we recorded the x-ray emission of highly
      charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange
      reactions between heavy ions in the solar wind and neutral gases in cometary
      comae. The spectra are complex and do not readily match predictions. We developed
      a charge exchange emission model that successfully reproduces the soft x-ray
      spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory.

PMID- 12791990
TI  - Climate-driven increases in global terrestrial net primary production from 1982
      to 1999.
AB  - Recent climatic changes have enhanced plant growth in northern mid-latitudes and
      high latitudes. However, a comprehensive analysis of the impact of global
      climatic changes on vegetation productivity has not before been expressed in the
      context of variable limiting factors to plant growth. We present a global
      investigation of vegetation responses to climatic changes by analyzing 18 years
      (1982 to 1999) of both climatic data and satellite observations of vegetation
      activity. Our results indicate that global changes in climate have eased several
      critical climatic constraints to plant growth, such that net primary production
      increased 6% (3.4 petagrams of carbon over 18 years) globally. The largest
      increase was in tropical ecosystems. Amazon rain forests accounted for 42% of the
      global increase in net primary production, owing mainly to decreased cloud cover
      and the resulting increase in solar radiation.

PMID- 12791991
TI  - Glacial refugia: hotspots but not melting pots of genetic diversity.
AB  - Glacial refuge areas are expected to harbor a large fraction of the intraspecific
      biodiversity of the temperate biota. To test this hypothesis, we studied
      chloroplast DNA variation in 22 widespread European trees and shrubs sampled in
      the same forests. Most species had genetically divergent populations in
      Mediterranean regions, especially those with low seed dispersal abilities.
      However, the genetically most diverse populations were not located in the south
      but at intermediate latitudes, a likely consequence of the admixture of divergent
      lineages colonizing the continent from separate refugia.

PMID- 12791992
TI  - In-depth view of structure, activity, and evolution of rice chromosome 10.
AB  - Rice is the world's most important food crop and a model for cereal research. At
      430 megabases in size, its genome is the most compact of the cereals. We report
      the sequence of chromosome 10, the smallest of the 12 rice chromosomes (22.4
      megabases), which contains 3471 genes. Chromosome 10 contains considerable
      heterochromatin with an enrichment of repetitive elements on 10S and an
      enrichment of expressed genes on 10L. Multiple insertions from organellar genomes
      were detected. Collinearity was apparent between rice chromosome 10 and sorghum
      and maize. Comparison between the draft and finished sequence demonstrates the
      importance of finished sequence.

PMID- 12791993
TI  - Equatorial retention of the contractile actin ring by microtubules during
      cytokinesis.
AB  - In most eukaryotes cytokinesis is brought about by a contractile actin ring
      located at the division plane. Here, in fission yeast the actin ring was found to
      be required to generate late-mitotic microtubular structures located at the
      division plane, and these in turn maintained the medial position of the actin
      ring. When these microtubular structures were disrupted, the actin ring migrated
      away from the cell middle in a membrane traffic-dependent manner, resulting in
      asymmetrical cell divisions that led to genomic instability. We propose that
      these microtubular structures contribute to a checkpoint control that retains the
      equatorial position of the ring when progression through cytokinesis is delayed.

PMID- 12791994
TI  - TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver.
AB  - Insulin resistance is a major hallmark in the development of type II diabetes,
      which is characterized by the failure of insulin to promote glucose uptake in
      muscle and to suppress glucose production in liver. The serine-threonine kinase
      Akt (PKB) is a principal target of insulin signaling that inhibits hepatic
      glucose output when glucose is available from food. Here we show that TRB3, a
      mammalian homolog of Drosophila tribbles, functions as a negative modulator of
      Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3
      disrupts insulin signaling by binding directly to Akt and blocking activation of
      the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db
      diabetic mice compared with those in wild-type mice. Hepatic overexpression of
      TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and
      glucose intolerance. Our results suggest that, by interfering with Akt
      activation, TRB3 contributes to insulin resistance in individuals with
      susceptibility to type II diabetes.

PMID- 12791995
TI  - Single neurons in the monkey hippocampus and learning of new associations.
AB  - The medial temporal lobe is crucial for the ability to learn and retain new
      declarative memories. This form of memory includes the ability to quickly
      establish novel associations between unrelated items. To better understand the
      patterns of neural activity during associative memory formation, we recorded the
      activity of hippocampal neurons of macaque monkeys as they learned new
      associations. Hippocampal neurons signaled learning by changing their stimulus
      selective response properties. This change in the pattern of selective neural
      activity occurred before, at the same time as, or after learning, which suggests
      that these neurons are involved in the initial formation of new associative
      memories.

PMID- 12791996
TI  - Programmed DNA deletion as an RNA-guided system of genome defense.
AB  - Genomewide DNA rearrangements occur in many eukaryotes during development, but
      their functions and mechanisms are poorly understood. Previous studies have
      implicated a sequence-recognition mechanism based on RNA-mediated interactions
      between nuclei in ciliated protozoa. In this study, we found that the process
      recognized and deleted a foreign gene integrated in a Tetrahymena chromosome,
      suggesting an unusual mechanism of genome surveillance. We further found that
      injection of double-stranded RNA into the cell at specific developmental stages
      triggers efficient deletion of the targeted genomic regions. Together the results
      indicate an RNA-based mechanism that directs genomewide DNA rearrangements and
      serves to disable invading genetic agents.

PMID- 12791997
TI  - Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan.
AB  - Although the role of Toll-like receptors in extracellular bacterial sensing has
      been investigated intensively, intracellular detection of bacteria through Nod
      molecules remains largely uncharacterized. Here, we show that human Nod1
      specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N
      acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative
      bacterial peptidoglycan, resulting in activation of the transcription factor NF
      kappaB pathway. Moreover, we show that in epithelial cells (which represent the
      first line of defense against invasive pathogens), Nod1is indispensable for
      intracellular Gram-negative bacterial sensing.

PMID- 12791998
TI  - Morphology and composition of the surface of Mars: Mars Odyssey THEMIS results.
AB  - The Thermal Emission Imaging System (THEMIS) on Mars Odyssey has produced
      infrared to visible wavelength images of the martian surface that show
      lithologically distinct layers with variable thickness, implying temporal changes
      in the processes or environments during or after their formation. Kilometer-scale
      exposures of bedrock are observed; elsewhere airfall dust completely mantles the
      surface over thousands of square kilometers. Mars has compositional variations at
      100-meter scales, for example, an exposure of olivine-rich basalt in the walls of
      Ganges Chasma. Thermally distinct ejecta facies occur around some craters with
      variations associated with crater age. Polar observations have identified
      temporal patches of water frost in the north polar cap. No thermal signatures
      associated with endogenic heat sources have been identified.

PMID- 12791999
TI  - Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm
      localization.
AB  - Myosin V is a dimeric molecular motor that moves processively on actin, with the
      center of mass moving approximately 37 nanometers for each adenosine triphosphate
      hydrolyzed. We have labeled myosin V with a single fluorophore at different
      positions in the light-chain domain and measured the step size with a standard
      deviation of <1.5 nanometers, with 0.5-second temporal resolution, and
      observation times of minutes. The step size alternates between 37 + 2x nm and 37 
      2x, where x is the distance along the direction of motion between the dye and
      the midpoint between the two heads. These results strongly support a hand-over
      hand model of motility, not an inchworm model.

PMID- 12792000
TI  - What is the role of healthcare managers in delivering safe care?

PMID- 12792001
TI  - Aviation safety: a model for health care?

PMID- 12792002
TI  - Drug use in sub-Saharan Africa: quality in processes--safety in use.

PMID- 12792003
TI  - Adverse drug events: what's the truth?

PMID- 12792004
TI  - Rights, risks, and autonomy: a new interpretation of falls in nursing homes.

PMID- 12792005
TI  - Labelling and patient knowledge of dispensed drugs as quality indicators in
      primary care in Botswana.
AB  - OBJECTIVES: To assess the quality of dispensing and patient knowledge of drugs
      dispensed in primary care in Botswana. SETTING: Thirty randomly assigned primary
      healthcare facilities in three districts of Botswana. PARTICIPANTS: Patients
      visiting clinics and health posts. DESIGN: Analysis of data from prospective
      participative observations of the drug dispensing process and interview of
      patients about their knowledge of drugs received immediately after dispensing.
      The quality of drug labelling was assessed by calculating mean labelling scores
      composed of five dispensing attributes: name of patient, and name, strength,
      dosage, and volume of the drug (incorrect or no labelling=0, 1 point for each
      correct labelling attribute; maximum score=5). Mean knowledge scores were
      obtained immediately after dispensing from patient recall of name and dosage of
      drug, duration of treatment, and reason for prescription (incorrect recall=0, 1
      point for each correct recall attribute; maximum score=4). RESULTS: 2994
      consecutive patient consultations were analysed. The mean labelling score was
      2.75. Family welfare educators and pharmacy technicians scored highest (3.15 and
      2.98, respectively) and untrained staff lowest (2.60). Factors independently
      associated with the labelling score were analgesics v other drugs, district,
      health posts v clinics, education of prescriber (nurse best), and years of
      experience of prescriber (4-11 years best). The mean patient knowledge score was
      2.50. The reason for prescription of the drug(s), dosage, duration of treatment,
      and name of the drug(s) was recalled by 92%, 83%, 44%, and 31% of patients,
      respectively. The qualification level of the dispenser was the strongest factor
      independently associated with the knowledge score. Antibiotics had the second
      lowest score, both for labelling (2.39) and patient knowledge (2.39). CONCLUSION:
      Only trained dispensing staff provided satisfactory quality of labelling.
      Patients had a fair knowledge of the drugs dispensed. The knowledge of drugs
      dispensed by family welfare educators was less than satisfactory. The labelling
      score is a useful indicator of the quality of dispensing, and the knowledge score
      of both the quality of prescribing and of dispensing. These indicators should be
      added to the WHO list of patient care indicators.

PMID- 12792006
TI  - Multidisciplinary medication review in nursing home residents: what are the most
      significant drug-related problems? The Bergen District Nursing Home (BEDNURS)
      study.
AB  - AIM: Based on a multidisciplinary review of drug use in nursing home residents,
      this study aimed to identify the most frequent clinically relevant medication
      problems and to analyse them according to the drugs involved and types of
      problems. METHODS: Cross sectional study auditing drug use by 1354 residents in
      23 nursing homes in Bergen, Norway. Data were collected in 1997. A
      physician/pharmacist panel performed a comprehensive medication review with
      regard to indications for drug use and active medical conditions. The drug
      related problems were subsequently classified according to the drugs involved and
      types of problems (indication, effectiveness, and safety issues). RESULTS: 2445
      potential medication problems were identified in 1036 (76%) residents.
      Psychoactive drugs accounted for 38% of all problems; antipsychotics were the
      class most often involved. Multiple psychoactive drug use was considered
      particularly problematic. Potential medication problems were most frequently
      classified as risk of adverse drug reactions (26%), inappropriate drug choice for
      indication (20%), and underuse of beneficial treatment (13%). CONCLUSIONS: Three
      of four nursing home residents had clinically relevant medication problems, most
      of which were accounted for by psychoactive drugs. The most frequent concerns
      were related to adverse drug reactions, drug choice, and probable undertreatment.

PMID- 12792008
TI  - QUOTE-HIV: an instrument for assessing quality of HIV care from the patients'
      perspective.
AB  - BACKGROUND: An HIV-specific version of the QUOTE questionnaire was developed to
      measure the quality of care of patients infected with HIV from the patients'
      perspective. The consistency and validity of the questionnaire was assessed.
      METHODS: Focus group discussions were held to select aspects for inclusion in the
      questionnaire that are important to patients with HIV. Item and inter-item
      analysis, factor analysis, and reliability analysis were performed to test the
      internal consistency and validity of the questionnaire. RESULTS: Twenty seven
      items (13 generic and 14 HIV specific) were used in the QUOTE-HIV questionnaire.
      Separate factor analyses of the generic and HIV specific aspects indicated that
      each loaded onto a single factor. The internal consistency of the total
      questionnaire was good (Cronbach's alpha >/=0.80). Feasibility of the
      questionnaire was shown by the diversity of importance and performance scores for
      general practitioners as well as for HIV specialists and AIDS nursing
      consultants. CONCLUSION: The QUOTE-HIV questionnaire is a useful instrument for
      measuring the quality of care from the perspective of HIV infected patients.

PMID- 12792007
TI  - Intensive support to improve clinical decision making in cardiovascular care: a
      randomised controlled trial in general practice.
AB  - OBJECTIVE: To evaluate the effects of feedback reports combined with outreach
      visits from trained non-physicians on the clinical decision making of general
      practitioners (GPs) in cardiovascular care. DESIGN: Pragmatic cluster controlled
      trial with randomisation of practices to support (intervention group) or no
      special attention (control group); analysis after 2 years. SETTING: 124 general
      practices in The Netherlands. PARTICIPANTS: 185 GPs. MAIN OUTCOME MEASURES:
      Compliance rates for 12 evidence-based indicators for the management of patients
      with hypertension, hypercholesterolaemia, angina pectoris, or heart failure. The
      evaluation relied on the prospective recording of patient encounters by the
      participating GPs. RESULTS: The GPs reported 30 101 clinical decisions at
      baseline and 22 454 decisions after the intervention. A significant improvement
      was seen for five of the 12 indicators: assessment of risk factors in patients
      with hypercholesterolaemia (odds ratio 2.04; 95% CI 1.44 to 2.88) or angina
      pectoris (3.07; 1.08 to 8.79), provision of information and advice to patients
      with hypercholesterolaemia (1.58, 1.17 to 2.13) or hypertension (1.55, 1.35 to
      1.77), and checking for clinical signs of deterioration in patients with heart
      failure (4.11, 2.17 to 7.77). Single handed practices, non-training practices,
      and practices with older GPs gained particular benefit from the intervention.
      CONCLUSIONS: Intensive support from trained non-physicians can alter certain
      aspects of the clinical decision making of GPs in cardiovascular care. The effect
      is small and the strategy needs further development.

PMID- 12792009
TI  - Adverse drug event trigger tool: a practical methodology for measuring medication
      related harm.
AB  - Adverse drug events continue to be the single most frequent source of healthcare
      mishaps, continually placing patients at risk of injury. This is not unexpected,
      given that drug treatment is the most common medical intervention and medication
      use is a highly complex, multidisciplinary, and largely manual process. Assessing
      the actual safety of drug use has been historically difficult, mainly because
      traditional methods such as chart audits and voluntary reporting of data have
      been shown to be expensive, insensitive, and largely ineffective for detecting
      mistakes in drug administration and drug related adverse clinical events (ADEs).
      Computerized methods for detecting ADEs, employing sentinel words or "triggers"
      in a patient's medical record, are effective but expensive and require customized
      software linkage to pharmacy databases. This paper describes the use of the
      "trigger tool", a relatively low cost and "low tech" modification of the
      automated technique. The adapted technique appears to increase the rate of ADE
      detection approximately 50-fold over traditional reporting methodologies.

PMID- 12792010
TI  - "At least Mom will be safe there": the role of resident safety in nursing home
      quality.
AB  - When family members admit a loved one to a nursing home, they expect that the
      facility will assure the physical safety of the residents. However, this does not
      always occur. Safety concerns persisting in at least some modern American nursing
      homes involve adverse drug events, injurious falls, pressure ulcers, problems
      with tube feeding, faulty communications or other breakdowns during transfer to
      or from hospital, and equipment breakdowns or mix-ups. The adversarial legal,
      economic, political, and media environment surrounding the US nursing home
      industry poses serious practical impediments to alleviating these safety concerns
      more effectively. However, resident safety comprises only one part of the larger
      quality improvement picture in the nursing home context. While the threat of
      negative legal repercussions may be necessary to address safety issues, a fuller
      concern about improving the quality of care and quality of life for nursing home
      residents will also involve the development and implementation of a combination
      of positive incentives for facilities to do better.

PMID- 12792011
TI  - About time: diagnostic guidelines that help clinicians.
AB  - Clinical guidelines often make recommendations on the use of diagnostic tests.
      Compared with sensitivity and specificity, the use of pre- and post-test
      probabilities allows a more explicit and rational selection and interpretation of
      diagnostic tests. Ideally, clinical guidelines relating to diagnosis should
      routinely incorporate this information to enhance individualised decision making.
      We report our experience of incorporating pre- and post-test probabilities into a
      guideline on the investigation of women with postmenopausal bleeding developed by
      the Scottish Intercollegiate Guidelines Network. Issues relating to their
      application are highlighted, including the limitations of available evidence on
      diagnostic tests and prevalence of disease, acceptability to guideline users, and
      the uncertain impact on actual clinical decision making. Despite these potential
      difficulties, the incorporation of data on pre- and post-test probabilities into
      the development and presentation of guideline recommendations may offer an
      important opportunity to make clinical decision making more transparent for both
      clinicians and patients.

PMID- 12792012
TI  - Methods for evaluation of small scale quality improvement projects.
AB  - Evaluation is an integral component of quality improvement and there is much to
      be learned from the evaluation of small scale quality improvement initiatives at
      a local level. This type of evaluation is useful for a number of different
      reasons including monitoring the impact of local projects, identifying and
      dealing with issues as they arise within a project, comparing local projects to
      draw lessons, and collecting more detailed information as part of a bigger
      evaluation project. Focused audits and developmental studies can be used for
      evaluation within projects, while methods such as multiple case studies and
      process evaluations can be used to draw generalised lessons from local
      experiences and to provide examples of successful projects. Evaluations of small
      scale quality improvement projects help those involved in improvement initiatives
      to optimise their choice of interventions and use of resources. Important
      information to add to the knowledge base of quality improvement in health care
      can be derived by undertaking formal evaluation of local projects, particularly
      in relation to building theory around the processes of implementation and
      increasing understanding of the complex change processes involved.

PMID- 12792013
TI  - Designing a quality improvement intervention: a systematic approach.
AB  - Most quality improvement or change management interventions are currently
      designed intuitively and their results are often disappointing. While improving
      the effectiveness of interventions requires systematic development, no specific
      methodology for composing intervention strategies and programmes is available.
      This paper describes the methodology of systematically designing quality of care
      improvement interventions, including problem analysis, intervention design and
      pretests. Several theories on quality improvement and change management are
      integrated and valuable materials from health promotion are added. One method of
      health promotion-intervention mapping-is introduced and applied. It describes the
      translation of knowledge about barriers to and facilitators of change into a
      concrete intervention programme. Systematic development of interventions,
      although time consuming, appears to be worthwhile. Decisions that have to be made
      during the design process of a quality improvement intervention are visualised,
      allowing them to serve as a starting point for a systematic evaluation of the
      intervention.

PMID- 12792014
TI  - Do house officers learn from their mistakes?
AB  - Mistakes are inevitable in medicine. To learn how medical mistakes relate to
      subsequent changes in practice, we surveyed 254 internal medicine house officers.
      One hundred and fourteen house officers (45%) completed an anonymous
      questionnaire describing their most significant mistake and their response to it.
      Mistakes included errors in diagnosis (33%), prescribing (29%), evaluation (21%),
      and communication (5%) and procedural complications (11%). Patients had serious
      adverse outcomes in 90% of the cases, including death in 31% of cases. Only 54%
      of house officers discussed the mistake with their attending physicians, and only
      24% told the patients or families. House officers who accepted responsibility for
      the mistake and discussed it were more likely to report constructive changes in
      practice. Residents were less likely to make constructive changes if they
      attributed the mistake to job overload. They were more likely to report defensive
      changes if they felt the institution was judgmental. Decreasing the work load and
      closer supervision may help prevent mistakes. To promote learning, faculty should
      encourage house officers to accept responsibility and to discuss their mistakes.

PMID- 12792016
TI  - Accessing the online evidence: a guide to key sources of research information on
      clinical and cost effectiveness.
AB  - Advice on how to access the best available online sources of research evidence on
      clinical and cost effectiveness published in three recent issues of Effectiveness
      Matters is reviewed.

PMID- 12792017
TI  - Evaluating Mesmerism, Paris, 1784: the controversy over the blinded placebo
      controlled trials has not stopped.

PMID- 12792018
TI  - Tracking adverse events in RCTs: lack of agreement among regulatory institutions.

PMID- 12792019
TI  - Reset of human neocortical oscillations during a working memory task.
AB  - Both amplitude and phase of rhythmic slow-wave electroencephalographic activity
      are physiological correlates of learning and memory in rodents. In humans,
      oscillatory amplitude has been shown to correlate with memory; however, the role
      of oscillatory phase in human memory is unknown. We recorded intracranial
      electroencephalogram from human cortical and hippocampal areas while subjects
      performed a short-term recognition memory task. On each trial, a series of four
      list items was presented followed by a memory probe. We found agreement across
      trials of the phase of oscillations in the 7- to 16-Hz range after randomly timed
      stimulus events, evidence that these events either caused a phase shift in the
      underlying oscillation or initiated a new oscillation. Phase locking in this
      frequency range was not generally associated with increased poststimulus power,
      suggesting that stimulus events reset the phase of ongoing oscillations.
      Different stimulus classes selectively modulated this phase reset effect, with
      topographically distinct sets of recording sites exhibiting preferential reset to
      either probe items or to list items. These findings implicate the reset of brain
      oscillations in human working memory.

PMID- 12792020
TI  - Nanobacteria-like calcite single crystals at the surface of the Tataouine
      meteorite.
AB  - Nanobacteria-like objects evidenced at the surface of the orthopyroxenes of the
      Tataouine meteorite in South Tunisia have been studied by scanning and
      transmission electron microscopies. A method of micromanipulation has been
      developed to ensure that exactly the same objects were studied by both methods.
      We have shown that the nanobacteria-like objects are spatially correlated with
      filaments of microorganisms that colonized the surface of the meteoritic pyroxene
      during its 70 years of residence in the aridic Tataouine soil. Depressions of a
      few micrometers in depth are observed in the pyroxene below the carbonates,
      indicating preferential dissolution of the pyroxene and calcite precipitation at
      these locations. The nanobacteria-like small rods that constitute calcium
      carbonate rosettes are well crystallized calcite single crystals surrounded by a
      thin amorphous layer of carbonate composition that smoothes the crystal edges and
      induces rounded shapes. Those morphologies are unusual for calcite single
      crystals observed in natural samples. A survey of recent literature suggests that
      the intervention of organic compounds derived from biological activity is likely
      in their formation.

PMID- 12792021
TI  - Evidence for neurogenesis in the adult mammalian substantia nigra.
AB  - New neurons are generated from stem cells in a few regions of the adult mammalian
      brain. Here we provide evidence for the generation of dopaminergic projection
      neurons of the type that are lost in Parkinson's disease from stem cells in the
      adult rodent brain and show that the rate of neurogenesis is increased after a
      lesion. The number of new neurons generated under physiological conditions in
      substantia nigra pars compacta was found to be several orders of magnitude
      smaller than in the granular cell layer of the dentate gyrus of the hippocampus.
      However, if the rate of neuronal turnover is constant, the entire population of
      dopaminergic neurons in substantia nigra could be replaced during the lifespan of
      a mouse. These data indicate that neurogenesis in the adult brain is more
      widespread than previously thought and may have implications for our
      understanding of the pathogenesis and treatment of neurodegenerative disorders
      such as Parkinson's disease.

PMID- 12792023
TI  - A framework for vulnerability analysis in sustainability science.
AB  - Global environmental change and sustainability science increasingly recognize the
      need to address the consequences of changes taking place in the structure and
      function of the biosphere. These changes raise questions such as: Who and what
      are vulnerable to the multiple environmental changes underway, and where?
      Research demonstrates that vulnerability is registered not by exposure to hazards
      (perturbations and stresses) alone but also resides in the sensitivity and
      resilience of the system experiencing such hazards. This recognition requires
      revisions and enlargements in the basic design of vulnerability assessments,
      including the capacity to treat coupled human-environment systems and those
      linkages within and without the systems that affect their vulnerability. A
      vulnerability framework for the assessment of coupled human-environment systems
      is presented.

PMID- 12792022
TI  - Selective impairment of hippocampal neurogenesis by chronic alcoholism:
      protective effects of an antioxidant.
AB  - A major pathogenic mechanism of chronic alcoholism involves oxidative burden to
      liver and other cell types. We show that adult neurogenesis within the dentate
      gyrus of the hippocampus is selectively impaired in a rat model of alcoholism,
      and that it can be completely prevented by the antioxidant ebselen. Rats fed for
      6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3%
      decrease in the number of new neurons and a 227-279% increase in cell death in
      the dentate gyrus as compared with paired controls. Neurogenesis within the
      olfactory bulb was not affected by alcohol. Our studies indicate that alcohol
      abuse, even for a short duration, results in the death of newly formed neurons
      within the adult brain and that the underlying mechanism is related to oxidative
      or nitrosative stress. Moreover, these findings suggest that the impaired
      neurogenesis may be a mechanism mediating cognitive deficits observed in
      alcoholism.

PMID- 12792024
TI  - Validation of the hexose transporter of Plasmodium falciparum as a novel drug
      target.
AB  - Chemotherapy of malaria parasites is limited by established drug resistance and
      lack of novel targets. Intraerythrocytic stages of Plasmodium falciparum are
      wholly dependent on host glucose for energy. Glucose uptake is mediated by a
      parasite-encoded facilitative hexose transporter (PfHT). We report that O-3
      hexose derivatives inhibit uptake of glucose and fructose by PfHT when expressed
      in Xenopus oocytes. Selectivity of these derivatives for PfHT is confirmed by
      lack of inhibition of hexose transport by the major mammalian glucose and
      fructose transporters (Gluts) 1 and 5. A long chain O-3 hexose derivative is the
      most effective inhibitor of PfHT and also kills P. falciparum when it is cultured
      in medium containing either glucose or fructose as a carbon source. To extend our
      observations to the second most important human malarial pathogen, we have cloned
      and expressed the Plasmodium vivax orthologue of PfHT, and demonstrate inhibition
      of glucose uptake by the long chain O-3 hexose derivative. Furthermore,
      multiplication of Plasmodium berghei in a mouse model is significantly reduced by
      the O-3 derivative. Our robust expression system conclusively validates PfHT as a
      novel drug target and is an important step in the development of novel
      antimalarials directed against membrane transport proteins.

PMID- 12792025
TI  - A simple energy-conserving system: proton reduction coupled to proton
      translocation.
AB  - Oxidative phosphorylation involves the coupling of ATP synthesis to the proton
      motive force that is generated typically by a series of membrane-bound electron
      transfer complexes, which ultimately reduce an exogenous terminal electron
      acceptor. This is not the case with Pyrococcus furiosus, an archaeon that grows
      optimally near 100 degrees C. It has an anaerobic respiratory system that
      consists of a single enzyme, a membrane-bound hydrogenase. Moreover, it does not
      require an added electron acceptor as the enzyme reduces protons, the simplest of
      acceptors, to hydrogen gas by using electrons from the cytoplasmic redox protein
      ferredoxin. It is demonstrated that the production of hydrogen gas by membrane
      vesicles of P. furiosus is directly coupled to the synthesis of ATP by means of a
      proton-motive force that has both electrochemical and pH components. Such a
      respiratory system enables rationalization in this organism of an unusual
      glycolytic pathway that was previously thought not to conserve energy. It is now
      clear that the use of ferredoxin in place of the expected NAD as the electron
      acceptor for glyceraldehyde 3-phosphate oxidation enables energy to be conserved
      by hydrogen production. In addition, this simple respiratory mechanism readily
      explains why the growth yields of P. furiosus are much higher than could be
      accounted for if ATP synthesis occurred only by substrate-level phosphorylation.
      The ability of microorganisms such as P. furiosus to couple hydrogen production
      to energy conservation has important ramifications not only in the evolution of
      respiratory systems but also in the origin of life itself.

PMID- 12792120
TI  - Abstracts of the World Congress of Nephrology. June 8-12, 2003. Berlin, Germany.

PMID- 12792026
TI  - Selenium-deficient diet enhances protein oxidation and affects methionine
      sulfoxide reductase (MsrB) protein level in certain mouse tissues.
AB  - Mammals contain two methionine sulfoxide (MetO) reductases, MsrA and MsrB, that
      catalyze the thioredoxin-dependent reduction of the S-MetO and R-MetO
      derivatives, respectively, to methionine. The major mammalian MsrB is a
      selenoprotein (except in the heart). Here, we show that there is a loss of MsrB
      activity in the MsrA-/- mouse that correlates with parallel losses in the levels
      of MsrB mRNA and MsrB protein, suggesting that MsrA might have a role in MsrB
      transcription. Moreover, mice that were grown on a selenium-deficient (SD) diet
      showed a substantial decrease in the levels of MsrB-catalytic activity, MsrB
      protein, and MsrB mRNA in liver and kidney tissues of both WT and MsrA-/- mouse
      strains. Whereas no significant protein-MetO could be detected in tissue proteins
      of young mature mice grown on a selenium-adequate diet, growth on the SD diet led
      to substantial accumulations of MetO in proteins and also of protein carbonyl
      derivatives in the liver, kidney, cerebrum, and cerebellum, respectively. In
      addition, accumulation of protein-MetO derivatives increased with age in tissues
      of mice fed with a selenium-adequate diet. It should be pointed out that even
      though the total Msr level is at least 2-fold higher in WT than in MsrA-/- mice,
      SD diet causes an equal elevation of protein-MetO (except in brain cerebellum)
      and carbonyl levels in both strains, suggesting involvement of other
      selenoproteins in regulation of the level of cellular protein-MetO accumulation.
      Furthermore, the development of the "tip-toe" walking behavior previously
      observed in the MsrA-/- mice occurred earlier when they were fed with the SD
      diet.

PMID- 12792121
TI  - Measuring cerebral autoregulation in stroke patients.

PMID- 12792122
TI  - A systematic review of single-session psychological interventions ('debriefing')
      following trauma.
AB  - BACKGROUND: Single-session psychological interventions such as psychological
      debriefing have become widely used following traumatic events. The evidence for
      their effectiveness has been widely debated. This review aimed to consider the
      evidence for the effectiveness of one-off early interventions within 1 month of a
      traumatic event. METHODS: A systematic review using the standard Cochrane
      Collaboration methodology. Literature searches of various databases were
      performed to identify randomised controlled trials. The methodological quality of
      the studies identified was determined using standard measures, and the results
      were pooled to consider the overall evidence for effectiveness. RESULTS: Eleven
      randomised controlled trials were found, all of individual or couple
      interventions. Three studies associated the intervention with a positive outcome,
      6 demonstrated no difference in outcome between intervention and non-intervention
      groups and 2 showed some negative outcomes in the intervention group (these
      studies had the longest follow-up periods). The methodological quality of the
      studies varied widely, but was generally poor. This review suggests that early
      optimism for brief early psychological interventions including debriefing was
      misplaced and that it should not be advocated for routine use. There remains an
      urgent need for randomised controlled trials of group debriefing and other early
      interventions.

PMID- 12792123
TI  - Use of antidepressant medications and the possible association with breast cancer
      risk. A review.
AB  - BACKGROUND: Antidepressant medication use has dramatically increased over the
      past decade, particularly for the newer classes such as selective serotonin
      reuptake inhibitors. While there is no question about the usefulness of these
      medications, it is important to review animal and epidemiologic studies that have
      evaluated the association between antidepressant medication use and the risk of
      breast cancer. METHODS: This paper reviews the scientific literature pertaining
      to the prevalence of and indications for antidepressant medication use, and the
      possible association between antidepressant medication use and breast cancer
      risk. RESULTS: Antidepressant medications are most commonly indicated for
      depressive disorders, and are also used for other conditions (e.g., anxiety
      disorders, personality disorders, and pain). In addition, antidepressants may be
      an effective alternative to estrogen therapy for the alleviation of hot flashes
      among peri-/postmenopausal women. Several epidemiologic studies have reported
      that certain antidepressants may be associated with a slightly increased breast
      cancer risk; however, the literature remains inconsistent. CONCLUSIONS: The
      possibility of an association between certain antidepressant medications and
      breast cancer risk has not been excluded, although further studies are needed
      before the body of scientific evidence can be conclusive. Evidence to date does
      not support a change in the current use of antidepressant medications.

PMID- 12792124
TI  - Posttraumatic embitterment disorder.
AB  - BACKGROUND: Adjustment and reactive disorders are a heterogeneous group of mental
      disorders. Diagnostic criteria are vague and scientific research is limited
      despite the fact that these disorders play a major role in clinical practice.
      METHODS: The 'posttraumatic embitterment disorder' (PTED) is introduced as a new
      concept for a subgroup of adjustment disorders. A case vignette and diagnostic
      criteria are presented. RESULTS: Core criteria of PTED are: (1) a single
      exceptional negative life event precipitates the onset of the illness; (2) the
      present negative state developped in the direct context of this event; (3) the
      emotional response is embitterment and feelings of injustice; (4) repeated
      intrusive memories of the event; (5) emotional modulation is unimpaired, patients
      can even smile when engaged in thoughts of revenge, and (6) no obvious other
      mental disorder that can explain the reaction. Additional symptoms are feelings
      of helplessness, self-blame, rejection of help, suicidal ideation, dysphoria,
      aggression, down-heartedness, seemingly melancholic depression, unspecific
      somatic complaints, loss of appetite, sleep disturbances, pain, phobic symptoms
      in respect to the place or to persons related to the event, reduced drive.
      Duration is longer than 3 months. Performance in daily activities and roles is
      impaired. CONCLUSIONS: PTED is a frequent disorder. The diagnosis of PTED can
      lead to specific therapeutic interventions. PTED can be discriminated from PTSD,
      depression, anxiety disorders, and other adjustment disorders.

PMID- 12792125
TI  - Dropout from brief psychotherapy within a combination treatment in bulimia
      nervosa: role of personality and anger.
AB  - BACKGROUND: To explore the personality, psychopathology, and clinical features of
      bulimic patients who do not complete psychotherapy, within a combined treatment.
      METHODS: 86 patients with bulimia nervosa (BN; DSM-IV) were evaluated before
      beginning treatment. The Eating Disorder Inventory II (EDI-II), State-Trait Anger
      Expression Inventory (STAXI), and the Temperament and Character Inventory (TCI)
      were administered to all patients. RESULTS: 3 subjects failed to engage in
      psychotherapy. Comparing patients who dropped out (n = 28) with those who did not
      drop out from psychotherapy (n = 55), significant differences were found in some
      psychopathologic (EDI-II, STAXI) and personality (TCI) variables. In particular,
      patients who dropped out from the treatment were more impulsive and more likely
      to feel anger; they were also less cooperative and less self-directive. No
      significant differences in sociodemographic, clinical variables and in response
      to fluoxetine were found between the two groups (dropout and completers).
      CONCLUSIONS: We found a characteristic profile in the bulimic patients who
      dropped out from brief psychotherapy, i.e., they are less cooperative and more
      predisposed to anger. These data suggest that dropping out in a subgroup of BN
      patients could be related to borderline personality traits and to difficulties in
      making and maintaining a therapeutic relationship. Implications for treatment are
      discussed.

PMID- 12792126
TI  - Cognitive-behavioral group therapy in obsessive-compulsive disorder: a randomized
      clinical trial.
AB  - BACKGROUND: The present study was designed to verify the efficacy of cognitive
      behavioral group therapy (CBGT) in reducing obsessive-compulsive symptoms and the
      intensity of overvalued ideas, as well as in improving the patient's quality of
      life. METHODS: Forty-seven patients meeting DSM-IV criteria for obsessive
      compulsive disorder (OCD) were randomly assigned to either 12 weekly CBGT
      sessions or a waiting list (control group). Treated patients were followed for
      three months. RESULTS: There was a significant reduction in the Yale-Brown
      Obsessive-Compulsive Scale (p < 0.001), in the National Institute of Mental
      Health Obsessive-Compulsive Scale (p < 0.001), in the Overvalued Ideas Scale (p <
      0.001), and a significant improvement in the quality of life in the four domains
      of the World Health Organization Quality of Life Assessment Scale: physical (p <
      0.001), psychological (p < 0.017), social (p < 0.018) and environmental (p <
      0.04). No significant reduction was found in the Hamilton Rating Scale for
      Anxiety (p = 0.111) and the Hamilton Rating Scale for Depression (p = 0.271). The
      concomitant use of anti-obsessional medications did not influence the results.
      The rate of improved patients was 69.6% in the treated group and 4.2% in the
      control group (p < 0.001). The therapeutic gains were maintained and an
      additional reduction in symptoms was observed during the 3-month follow-up
      period. CONCLUSIONS: The results suggest that CBGT is effective in reducing the
      intensity of OCD symptoms and of overvalued ideas, and that it improves the OCD
      patient's quality of life in a short period of time.

PMID- 12792127
TI  - Anxiety sensitivity profile: dimensional structure and relationship with
      temperament and character.
AB  - BACKGROUND: Anxiety sensitivity (AS), the belief that bodily sensations have
      harmful consequences, is a reliable predictor of panic attacks in both clinical
      and nonclinical populations. Recently, a new measure of AS has been proposed. The
      AS profile (ASP) was designed to be a more comprehensive measure of AS, and to be
      more suitable for the measurement of different AS dimensions. Preliminary
      evidence (college student sample) suggests that the ASP has 4 dimensions. In the
      present study, the dimensional structure of the ASP was further investigated, as
      well as its relationship with temperament and character traits. METHODS:
      Exploratory and confirmatory factor analysis of ASP scores in two large samples
      of psychiatric outpatients and nonclinical controls (combined n = 742).
      Correlations and partial correlations of ASP with temperament and character.
      RESULTS: Exploratory factor analysis yielded a single AS factor. However,
      confirmatory factor analysis showed that the 6-dimensional structure, as Taylor
      and Cox had originally intended it, might be a defendable solution. However, the
      number of items is much too high, with many subscales consisting of semantic
      clusters. ASP scores were found to be weakly related to the temperament dimension
      harm avoidance, corroborating earlier findings that were not statistically
      significant because of small sample sizes. CONCLUSIONS: The ASP may be shortened
      from 60 to 24 items without loss of reliability or content. Future studies using
      challenge paradigms and studies with general hospital patients may further
      investigate the usefulness of a shortened version of the ASP.

PMID- 12792128
TI  - Routine monitoring of outcome over 11 years in a residential behavioural
      psychotherapy unit.
AB  - BACKGROUND: Though research trials have to rate clinical outcome, few units
      monitor outcome of their routine care over many years. We report such monitoring
      to evaluate therapy over time and under changing operating and economic
      conditions. METHOD: Clinical outcome data were collected routinely over 11 years
      in a behavioural psychotherapy unit whose residential patients mostly had severe,
      chronic obsessive-compulsive disorder (OCD) treated by self-exposure therapy.
      Data were from 218 referrals during 4 of the 11 available years. RESULTS: In each
      of the 4 time periods, the patients improved consistently and highly
      significantly by 30-50% on symptoms and disability, which resembled outcome in a
      multi-centre controlled trial. There were almost no significant differences in
      pre-treatment ratings between patients who attended follow-up, patients who
      completed residential treatment but not follow-up and those who did not complete
      residential treatment. When the unit became a hostel and the UK government
      introduced an internal market, more chronic patients were admitted who often
      lived far away. CONCLUSIONS: The fact that successive OCD cohorts had improved
      comparably by discharge suggests there was no 'burn-out' in staff standards of
      care over 11 years, and no loss of gains when the unit became a more cost
      effective hostel.

PMID- 12792129
TI  - From health to disease: a new approach to study the emergence of psychosomatic
      symptoms.

PMID- 12792130
TI  - Management of giant cell arteritis. Our 27-year clinical study: new light on old
      controversies.
AB  - Giant cell arteritis (GCA) is the prime medical emergency in ophthalmology
      because of its dreaded complication of visual loss in one or both eyes, which is
      preventable if these patients are diagnosed early and treated immediately and
      aggressively with systemic corticosteroids. However, there is much controversy on
      diagnostic criteria and various aspects of steroid therapy to prevent visual
      loss. We discuss in detail the reasons for the controversy, clinical criteria to
      establish a definite early diagnosis of GCA, and its management. To provide new
      information on corticosteroid therapy in GCA, we also present our 27-year planned
      study on steroid therapy in GCA in 145 temporal artery biopsy-confirmed GCA
      patients (96 with and 49 without visual loss) seen and followed for 6 weeks or
      more in our clinic. The median follow-up time was 2.43 years, with interquartile
      range of 1-6 years (range 6 weeks to 20.2 years). Intravenous megadose steroid
      therapy was initially given to 33% followed by oral steroids, while the rest had
      only the oral therapy. The median starting oral prednisone dose was 80 mg/day,
      with 40% on >/=100 mg/day. We found that the most reliable and sensitive
      parameters to regulate and taper down steroid therapy were the levels of
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and NOT
      systemic symptoms. All patients were maintained at the high-dose prednisone till
      both the ESR and CRP had stabilized at low levels (that usually took 2-3 weeks),
      after which very gradual tapering of prednisone was started, guided by the ESR
      and CRP levels only. The median time to reach the lowest maintenance dose of
      prednisone at which the ESR and CRP stayed low and stable was 48.7 months (95%
      CI: 34.6, 71.4 months), and the median lowest prednisone dose achieved was 7
      mg/day (interquartile range of 1-16 mg/day). A comparison of patients with and
      without visual loss showed no significant difference in the time to attain the
      lowest dose (p = 0.359). Our study showed that no generalization is possible for
      tapering down of prednisone and there is no set formula because of the infinite
      variation between individuals. Only 10 (7 without visual loss, 3 with visual
      loss) of 145 patients were able to stop the therapy and maintain stable ESR and
      CRP levels. We found that only 4% of GCA patients with visual loss showed any
      visual improvement with high-dose steroid therapy, and 4% developed further
      visual loss during the first 5 days of high-dose steroid therapy but none after
      that. Our studies found no evidence that intravenous megadose steroid therapy was
      more effective than oral therapy in improving vision or preventing visual
      deterioration due to GCA.

PMID- 12792131
TI  - Normal values of short-wavelength automated perimetry.
AB  - BACKGROUND: The purpose of this study was to evaluate short-wavelength automated
      perimetry (SWAP, i.e., blue-yellow) in normal volunteers and to review the
      current normal values provided by the manufacturer. METHODS: 28 eyes of 28 normal
      subjects (age range 21-48 years, mean age 36.5 years) had SWAP (Octopus 101, two
      phases of program G2, Interzeag AG, Schlieren, Switzerland). All subjects had
      normal eye examinations, refractive errors with spherical equivalents <5 diopters
      and astigmatism <2 diopters, normal intraocular pressures, no history of diseases
      affecting the visual field or nerve fiber layer, and normal white-white automated
      perimetry (Octopus 101, program G2). RESULTS: 21% of the subjects (6/28) had to
      be excluded since visual field testing was not reliable (reliability factor >5%).
      With the normal values provided by the manufacturer, only 45% of the remaining
      subjects (10/22) had all other indices within normal limits. With the appropriate
      normal values based on the multicenter SWAP Octopus 101 study, 11% (3/28) were
      beyond the normal range: all had abnormal high sensitivities - 2 due to false
      positive response. The normal value range for the index Mean Defect is remarkably
      wide (5.-, median, 95.- percentile: -4.4, -0.5, +5.3 dB, respectively). The
      normal value range for the index Loss Variance is surprisingly low and similar to
      standard perimetry (5.-, median, 95.- percentile: -1.7, 6.8, +21.2 dB(2),
      respectively). CONCLUSION: SWAP with the Octopus G2 program reaches appropriate
      specificity but only if the correct normal values of the multicenter SWAP Octopus
      101 study are used. The variability between subjects is remarkably large. The
      variability within a visual field is similar for SWAP and standard perimetry as
      reflected by similar values for the visual field index Loss Variance. Further
      studies have to establish the sensitivity to detect a disease for SWAP on the
      Octopus 101.

PMID- 12792132
TI  - Comparison of three techniques for repair of involutional lower lid entropion: a
      three-year follow-up study.
AB  - OBJECTIVE: The aim of this study was to quantify the efficacy of three different
      surgical techniques for entropion repair in a 3-year follow-up study: (1) the Fox
      procedure, (2) everting sutures and (3) a modified technique of lower lid
      retractor plication. METHODS: We included in our study 32 eyelids of 32
      consecutive patients with involutional lower lid entropion; 10 lids underwent the
      Fox procedure, 13 the everting sutures and 9 the modified retractor plication. We
      evaluated the pre- and postoperative horizontal lid laxity (HLL), the pre- and
      postoperative lower lid excursion (LLE) and the number of recurrences in each
      patient group. Statistical analysis was performed with the non-parametric Mann
      Whitney test and the exact Fisher's test where appropriate. RESULTS: Only the
      modified retractor plication technique showed statistically significant
      differences in HLL and LLE (p < 0.05). In the group treated with this technique,
      there was a lower incidence of entropion recurrence (p < 0.05). The everting
      suture technique showed a statistically significant improvement of the LLE only
      (p < 0.05). The Fox procedure did not show any statistically significant
      improvement of the studied parameters. CONCLUSIONS: The modified retractor
      plication technique gave the best results in terms of improvement of HLL and LLE
      and a lower incidence of entropion recurrence compared to the two other
      techniques studied.

PMID- 12792133
TI  - Evaluation of the effect of aging on retinal nerve fiber layer thickness measured
      by optical coherence tomography.
AB  - PURPOSE: To evaluate the relationship between age and retinal nerve fiber layer
      (RNFL) thickness in normal subjects, as measured by optical coherence tomography
      (OCT). METHODS: One hundred and forty-four normal subjects (144 eyes), ranging
      from 16 to 84 years of age, were enrolled in this cross-sectional study. The RNFL
      thickness was determined using OCT with three circle scans 3.4 mm in diameter.
      RESULTS: The average RNFL thickness was inversely correlated with age (r = 
      0.348, p < 0.001). Analyzing the quadrants as a parameter, RNFL thickness in the
      superior, temporal and inferior quadrants also decreased with age. Using 30
      degree segments, there were significant correlations between age and the RNFL
      thickness of temporal segments (7-11 o'clock). The average RNFL thickness had the
      highest correlation among all parameters (r = -0.348, p < 0.001). Regarding nasal
      quadrant thickness, RNFL ratios (average, superior, temporal and inferior RNFL
      thickness relative to the nasal quadrant thickness) were not significantly
      correlated with age. The refractive error did not affect RNFL thickness (r =
      0.091, p = 0.276). CONCLUSION: Our study revealed that RNFL thickness, in
      particular in the temporal quadrant, measured by OCT significantly decreased with
      age. Age has to be taken into consideration when we compare RNFL thickness
      between normal and glaucomatous eyes.

PMID- 12792134
TI  - Long-term follow-up after transscleral diode laser photocoagulation in refractory
      glaucoma.
AB  - BACKGROUND AND OBJECTIVE: Patients affected by glaucoma refractory to medical or
      surgical treatment are difficult to treat. The aim of this study was to evaluate
      the long-term effect of contact transscleral diode laser cyclophotocoagulation
      (DLPC) on intraocular pressure (IOP) and on visual acuity of these patients.
      PATIENTS AND METHODS: One hundred and twenty eyes of 107 patients suffering from
      refractory glaucoma and treated with DLPC were followed at the Eye Clinic of
      Verona University for an average of 26 +/- 8 months. Mean age was 57 +/- 26
      years. IOP, visual acuity, and ocular complications were analyzed. RESULTS: A
      total of 207 treatments were given. More than one treatment was given in 55 eyes
      (45.8%). Mean pretreatment IOP was 30.4 +/- 3.1 mm Hg. At the last follow-up,
      mean IOP was 20.3 +/- 1.8 mm Hg. Mean total medications were reduced from 4.5 +/-
      0.5 to 2.3 +/- 0.3. No serious complications occurred in the 207 treatments.
      Visual acuity remained stable in 66 eyes (55%), improved in 25 eyes (20.8%), and
      decreased in 29 eyes (24.2%). CONCLUSIONS: DLPC was effective in lowering IOP in
      eyes with refractory glaucoma. It also served to reduce the number of
      antiglaucoma medications, thus improving both the quality of life of the patients
      and their compliance to therapy. This procedure is relatively safe, very fast and
      easy to learn. However, careful attention is required to determine the exact
      position of the ciliary body in malformative glaucoma. Multiple treatments may be
      required to control IOP.

PMID- 12792135
TI  - Effect of hospitalization on intraocular pressure in patients with normal-tension
      glaucoma.
AB  - OBJECTIVE: To investigate the effect of hospitalization on intraocular pressure
      (IOP) in patients with normal-tension glaucoma (NTG). METHODS: The study was
      conducted in 52 patients with a definite diagnosis of NTG. The correlation
      between IOP measured from 9.00 a.m. to 12.00 p.m. on an outpatient basis within 3
      months each prior to and after hospitalization (ambulatory IOP) and IOP measured
      during the same time period after admission (inpatient IOP) was investigated in
      NTG patients. RESULTS: Inpatient IOP (13.9 +/- 2.4 mm Hg) was significantly lower
      than ambulatory IOP (15.2 +/- 2.1 mm Hg), with a difference of 1.3 +/- 2.0 mm Hg
      (p < 0.01). The difference between inpatient IOP and ambulatory IOP was
      negatively correlated with inpatient IOP (r = 0.58, p < 0.01). CONCLUSIONS: These
      results revealed that hospitalization decreased IOP in NTG patients, with the
      decrease being particularly pronounced in cases of low ambulatory IOP.
      Interpretation of inpatient IOP should be carefully included in glaucoma
      treatment.

PMID- 12792137
TI  - Age- and gender-related differences in human lacrimal fluid peroxidase activity.
AB  - There is evidence to suggest that estrogen influences lacrimal fluid peroxidase
      activity in women. In this study we investigated changes in peroxidase activity
      related to ageing and gender. These changes might help to explain the common
      problem of dry-eye syndrome in menopausal women. Unstimulated tears were
      collected from 70 healthy subjects of both sexes (age range 24-90 years). Tear
      samples were collected from 9 to 10 a.m., when peroxidase activity remained
      stable. In women, lacrimal fluid peroxidase activity decreased significantly
      during the menopause (p < 0.05 by one-way ANOVA), and thereafter remained
      unchanged. Conversely, in men, lacrimal fluid peroxidase activity decreased
      later, declining significantly only towards the age of 80 (p < 0.05). Lacrimal
      fluid peroxidase activity differs in men and women: the gender-related difference
      accentuates during ageing, probably owing to changing estrogen levels.

PMID- 12792136
TI  - Changing antiglaucoma therapy from timolol to betaxolol: effect on ocular blood
      flow.
AB  - The aim of the present study was to investigate the effect of a therapy change
      from timolol to betaxolol on ocular blood flow in patients with open-angle
      glaucoma. This randomized double-blind study comprised 34 consecutive patients
      with open-angle glaucoma, already treated with either timolol alone or in
      combination with other antiglaucoma agents. The patients were randomly allocated
      to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present
      timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal
      blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile
      choroidal blood flow was assessed by laser interferometric measurement of fundus
      pulsation amplitude. Ocular blood flow measurement as well as systemic
      hemodynamic and intraocular pressure (IOP) measurements were performed at
      baseline and 1 week and 1 and 3 months after the therapy change. Visual field
      testing was performed at baseline and at 3 months. After 3 months of treatment
      with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal
      blood flow were significantly altered. The power to detect a 9% change in
      pulsatile choroidal blood flow and a 20% change in retinal blood flow in the
      present study was 90%. The IOP was not significantly altered in either group. In
      contrast, visual fields slightly improved after betaxolol treatment compared to
      baseline (p = 0.047), but this effect was not significant versus timolol.
      Changing therapy from timolol to betaxolol has no effect on ocular blood flow in
      patients with open-angle glaucoma.

PMID- 12792138
TI  - Elevated nitric oxide level in aqueous humor of AIDS patients with
      cytomegalovirus retinitis.
AB  - Human cytomegalovirus (HCMV) retinitis is the most common ocular opportunistic
      infection in AIDS. It often leads to blindness if left untreated. The questions
      as to how HCMV infection causes retinal immunopathogenesis and visual destruction
      in AIDS patients have not been completely established. Here we reported that the
      nitric oxide (NO) levels in aqueous humor samples in 10 AIDS patients with CMV
      retinitis (104.3 +/- 27.1 microM) were higher than the levels in 7 AIDS patients
      without CMV retinitis (36.1 +/- 10.4 micro M; p < 0.001). After ganciclovir
      treatment, the NO level in the vitreous body of 5 patients declined dramatically
      (53.4 +/- 11.8 micro M). By using immunohistochemistry assay, we found that the
      aggregates of macrophages infiltrated in the CMV-infected retina of 4 AIDS
      patients. Moreover, the expression of inducible-form NO synthase was detected in
      the infected retina of these patients. These results suggest that NO production
      in the eye may play a fundamental role in the immunopathogenesis of AIDS patients
      with CMV retinitis.

PMID- 12792140
TI  - Conservative treatment of vertical diplopia in a patient with silent sinus
      syndrome.
AB  - Silent sinus syndrome is a rare disease of the maxillary sinus characterized by
      bony absorption processes leading to progressive sinus wall thinning with
      consecutive enophthalmos and hypoglobus. It represents a benign cause of acquired
      enophthalmos and is often accompanied by painless vertical diplopia, the latter
      treated surgically in all cases published to date. We report a 56-year-old
      patient with silent sinus syndrome in whom vertical diplopia was treated with
      prisms showing that conservative treatment alone may, in mild cases, be an
      effective alternative to reconstructive surgery.

PMID- 12792139
TI  - Dietary sugar and salt represent real risk factors for cataract development.
AB  - Dietary sugar and salt represent etiological risk factors of human cataract. To
      verify etiological data on the basis of histological findings, 9 pigs with a body
      weight of 40 kg, 3 months of age, in groups of 3 were continuously fed with 5% of
      refined dietary sugar (sucrose - C(12)H(22)O(11)), 0.5% of salt (NaCl) and a
      sugar-salt mixture (2.5 + 0.25% accordingly) in their crude (unboiled) meal food
      during 3 months, which resulted in minor cataractous changes in the lens. In the
      second experiment, 10 weight- and age-matched animals were fed a chronic sugar
      and intermittent salt diet during 6 months; the other 10 animals served as
      controls. During the second experiment, crystallin leakage into the aqueous humor
      of the lens was detected, and a marked swelling of the lens fibers and fiber tips
      was noticed, indicating that excessive amounts of dietary sugar and salt are risk
      factors for the development of cataract in normal (nondiabetic) animals.

PMID- 12792141
TI  - An evidence-based medicine approach to the evaluation of the role of exogenous
      risk factors in sporadic amyotrophic lateral sclerosis.
AB  - An evidence-based medicine approach was applied to evaluate analytic studies of
      exogenous risk factors for amyotrophic lateral sclerosis (ALS) published since
      1991. Classification systems for evaluating the literature and for drawing
      conclusions based on the class of available evidence were developed, modeled on
      those used by national societies. Considerations regarding the impact on the
      general public of confirming a role for putative risk factors were made explicit.
      There was evidence in support of smoking being a probable ('more likely than
      not') risk factor for ALS. Smoking has broad public health impact, no redeeming
      features, and is a modifiable risk factor. Evidence supported the conclusion that
      the following were probably not risk factors for ALS: trauma, physical activity,
      residence in rural areas and alcohol consumption. Evidence-based medicine
      methodology does not permit calculation of the magnitude of type I or type II
      errors in drawing these conclusions. New evidence may change these conclusions.
      Recommendations for future research include: draw on clinical trial methodology
      in designing future, confirmatory, case-control studies; consider utilizing
      cohort studies, recognizing the longer timelines for these to come to fruition;
      accord priority to investigating putative risk factors with greatest public
      health impact. Advances in study methodology may lead to development of finite
      research cycles for individual putative risk factors for sporadic ALS.

PMID- 12792142
TI  - Incidence of amyotrophic lateral sclerosis in the local health district of
      Ferrara, Italy, 1964-1998.
AB  - One of the epidemiologic characteristics of amyotrophic lateral sclerosis (ALS)
      still under discussion is whether the incidence of ALS is increasing over time.
      We performed a new investigation expanding our previous study of ALS in the local
      health district (LHD) of Ferrara, northern Italy, to determine whether there have
      been any changes in the incidence of ALS in the years 1964-1998. We used a
      complete enumeration approach by reviewing all possible sources of case
      collection available in the study area. We selected all patients with definite
      and probable ALS according to the World Federation of Neurology criteria. The
      mean annual crude incidence rate for 1964-1998 was 1.63 per 100,000 population
      (95% CI 1.31-2.00). An increase in incidence from 1.07 to 2.19 per 100,000
      population was observed during the study period. It was greater in women and in
      individuals of 70 years old and over. Substantial population ageing occurred in
      the LHD of Ferrara during the study period and it was more prominent in women.
      This increase in incidence seems to be explained mainly by the ageing of the
      population. Moreover, greater precision in diagnosis of ALS in elderly women,
      rather than better case ascertainment of diagnosed patients, may have contributed
      to the increase. The role of environmental factors cannot be excluded, but based
      on the present findings, it seems to be of little importance.

PMID- 12792143
TI  - A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis.
AB  - We report the clinical and laboratory findings in the largest kindred so far
      recorded with familial amyotrophic lateral sclerosis due to an A4T mutation in
      the SOD1 gene. The age of onset ranged from 32 to 60 years, with a mean of 46
      years. Weakness in the legs was the most frequent early symptom and there was a
      predominance of lower motor neuron signs. The mean time from onset of symptoms to
      death was 14 months. One man with onset at the age of 37 has shown a slowly
      developing form and is currently alive 76 months after diagnosis (October 2002),
      although severely affected. The A4T mutation, with one exception, was of similar
      severity to the A4V mutation.

PMID- 12792144
TI  - Spouses and unrelated friends of probands as controls for stroke genetics
      studies.
AB  - To plan a multisite, ischemic stroke genetic study, stroke patients were surveyed
      about the availability and characteristics of a convenience sample of
      spouse/friend controls. 65% of all stroke-affected probands reported a living
      spouse. A more detailed survey was conducted at the University of Virginia,
      Charlottesville, Va., USA: 51% of stroke patients reported a living, stroke-free
      spouse who would be willing to serve as a control, and 49% reported having a
      stroke-free friend who would be willing to serve as a control. Overall, 75% of
      stroke patients reported at least 1 individual willing to participate as a
      control. Cases without an identified control were more likely to be non-white
      (48%) than were cases with a control (13%; p = 0.00004). Cases were older than
      controls (67.3 vs. 59.2 years; p = 0.000002), and a greater proportion of cases
      than controls were male (57 vs. 33%; p = 0.0002). Without proper attention to
      matching, the use of a spouse/friend convenience sample would result in
      imbalances in basic demographic characteristics.

PMID- 12792145
TI  - A descriptive study of Guillain-Barre syndrome in high and low Campylobacter
      jejuni incidence regions of Michigan: 1992-1999.
AB  - The incidence rate of Guillain-Barre syndrome (GBS) was compared between high and
      low Campylobacter jejuni incidence counties in Michigan, USA, between 1992 and
      1999. Data on GBS was obtained from cases reported to the Michigan Department of
      Community Health. Poisson confidence intervals were used to compare incidence
      rates. There was no significant difference in the overall rate between high and
      low C. jejuni incidence regions in Michigan. Though no differences in age
      specific, gender-specific, and seasonal rates were significant, GBS was more
      common in spring and summer in the high C. jejuni incidence region than in the
      low C. jejuni incidence region. Differences in the distribution of cases by age
      group and gender are described, though no difference was statistically
      significant.

PMID- 12792146
TI  - Reproductive factors have low impact on the risk of different primary brain
      tumours in offspring.
AB  - OBJECTIVES: The aim of our study was to investigate whether reproductive factors
      influence the risk of primary brain tumours (PBT) in offspring. METHODS: Data on
      all deliveries in two Swedish counties from 1955 to 1990 were extracted from two
      birth registries. The follow-up period closed at the end of 1994, with subjects
      followed up to early middle age. Incidence rates of malignancy for 1958-1994 were
      obtained from the Swedish Cancer Registry. Standardised incidence ratios (SIR)
      and relative risks were calculated for astrocytomas, primitive neuroectodermal
      tumour, ependymoma and meningiomas in offspring. RESULTS: Few associations were
      detected. High birth weight indicated an increased risk for astrocytomas grade I
      and II for all primary brain tumours, and the risk was close to significance for
      astrocytomas grade I-II (SIR = 3.64; CI = 0.98-9.31). For children under 15 years
      of age the risk for astrocytomas grade I and II was further increased (SIR =
      4.44; CI = 1.19-11.38). CONCLUSIONS: A consistent pattern of non-association
      indicated a low impact of intrauterine environment on the future development of
      primary brain tumours in offspring up to early middle age.

PMID- 12792147
TI  - The current availability of neurological in-patient services in post-communist
      central and eastern European countries.
AB  - BACKGROUND AND PURPOSE: Limited information can be obtained as to the
      availability of neurological in-patient services in the former communist
      countries of Eastern and Central Europe. The objective was to analyse data
      received directly from representatives of the particular countries. METHODS: The
      data were collected under the auspices of the 'First European Cooperation
      Neurology Workshop' held in April 2000, in Trest, Czech Republic. Neurologists
      from 15 post-communist countries provided information from their respective
      countries. Linear trends in graphs including the reliability value R(2) were used
      in the analysis of correlations. RESULTS: Data from 14 countries were assembled
      and trends were analysed. CONCLUSIONS: Direct relationships were found between:
      (1) the average department size and the average catchment area (R(2) = 0.1015);
      (2) the percentage of districts with a neurological in-patient department and the
      gross national product (GNP) per capita (R(2) = 0.1359); (3) the average
      neurological department size and the GNP per capita (R(2) = 0.1135), and (4) the
      average length of treatment and the number of neurological beds/100,000
      inhabitants (R(2) = 0.1745). Inverse relationships were found between: (1) the
      number of neurological beds/100,000 inhabitants and the average hospital
      catchment area (R(2) = 0.2105), and (2) the number of neurological beds/100,000
      inhabitants and the GNP per capita (R(2) = 0.1144).

PMID- 12792148
TI  - Molecular genetic and endocrine mechanisms of hair growth.
AB  - The prenatal morphogenesis of hair follicles depends upon a precisely regulated
      series of molecular genetic processes. Hormones and their receptors play
      prominent roles in modulating postnatal hair cycling, which recapitulates some
      aspects of morphogenesis. The responses to androgen are the most obvious of
      these. The postnatal androgen sensitivity of pilosebaceous units in different
      skin areas is programmed during prenatal development to permit clinical outcomes
      such as hirsutism and pattern baldness. Thyroid hormone, glucocorticoids, insulin
      like growth factor-I, and prolactin have clinically significant effects on
      specific aspects of hair growth. The nuclear receptors vitamin D receptor and
      retinoid X receptor are essential for postnatal hair cycling. Other hormones have
      less clear effects on hair growth. Advances in research on the interaction of
      hormone target genes with the biological processes involved in hair morphogenesis
      and cycling can be expected to improve management of hirsutism and alopecia.

PMID- 12792149
TI  - IFN-gamma increases the hGH gene promoter activity in rat GH3 cells.
AB  - AIM: To study the effect(s) of interferon gamma (IFN-gamma) on the activity of
      human growth hormone (hGH) gene promoter in rat pituitary GH3 cells and the
      molecular mechanism underlying the effect(s). METHODS: Cell transfection and
      luciferase reporter gene were used. RESULTS: IFN-gamma (10(2) and 10(3) U/ml)
      increased the activity of hGH in GH3 cells. The addition of the mitogen-activated
      protein kinase inhibitor PD98059 (40 micromol/l) to the cells blocked the
      stimulatory effect of IFN-gamma. Neither overexpression of Pit-1 nor inhibiting
      Pit-1 expression affected IFN-gamma induction of hGH promoter activity. To
      identify the DNA sequence that mediated the effect of IFN-gamma, four deletion
      constructs of hGH gene promoter were created. The stimulatory effect of IFN-gamma
      was abolished following deletion of the -250 to -132 fragment. CONCLUSIONS: IFN
      gamma increases the activity of hGH gene promoter in rat pituitary GH3 cells.
      This stimulatory effect of IFN-gamma appears to require the intracellular mitogen
      activated protein kinase-dependent signaling pathway. The effect of IFN-gamma
      requires the promoter sequence that spans the -250 to -132 fragment of the gene,
      but is unrelated to Pit-1 protein.

PMID- 12792150
TI  - Osteoporosis in male hypogonadism: responses to androgen substitution differ
      among men with primary and secondary hypogonadism.
AB  - BACKGROUND: No randomized study exists comparing the effects of different modes
      of androgen substitution on bone mineral density (BMD). METHODS: We performed a
      prospective, randomized, trial assigning 53 hypogonadal men to the following
      treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg
      p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single
      subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was
      determined by peripheral quantitative computed tomography. RESULTS: At baseline,
      men with secondary hypogonadism (n = 33) had a lower BMD (-1.52 +/- 0.23 SDS; Z
      scores) than men with primary hypogonadism (n = 20, -0.87 +/- 0.23 SDS, p <
      0.01). In men with primary hypogonadism, the BMD increased dose dependently
      (crystalline testosterone +7.0 +/- 1.3%, testosterone enanthate +4.8 +/- 0.2%,
      testosterone undecanoate +3.4 +/- 2.5%, mesterolone +0.8 +/- 1.6%) after 6 months
      of therapy. Only secondary hypogonadal men treated with testosterone enanthate
      experienced an increase of the BMD. CONCLUSIONS: In primary hypogonadal men the
      BMD responds dose dependently to testosterone substitution, whereas in secondary
      hypogonadism only testosterone enanthate treatment significantly increased the
      BMD.

PMID- 12792151
TI  - Relations of serum interleukin 18 levels to serum lipid and glucose
      concentrations in an apparently healthy adult population.
AB  - AIM: To investigate the associations between serum interleukin (IL) 18
      concentrations and indices of lipid and carbohydrate metabolism in healthy
      adults. METHODS: Fasting serum concentrations of IL-18, glucose, total
      cholesterol, triglyceride, and high- and low-density lipoprotein cholesterols
      were measured in 570 apparently healthy adults. RESULTS: Univariate linear and
      partial regression analyses showed that the serum IL-18 concentration was
      positively correlated with serum triglyceride and glucose concentrations in both
      obese and diabetic subjects after controlling for the confounding effects of age,
      sex, and body mass index. CONCLUSION: IL-18 may be associated with obesity and
      glucose intolerance.

PMID- 12792152
TI  - Assessing short-statured children for growth hormone deficiency.
AB  - AIM: To optimize the workup of short-statured children by defining the most
      appropriate tools for diagnosing growth hormone (GH) deficiency. METHODS:
      Patients were assigned to prepubertal (n = 113) or pubertal (n = 112, including
      25 boys primed with testosterone) age groups. Mean plasma GH concentration during
      sleep, GH peak after provocative test, and insulin-like growth factor I (IGF-I)
      were measured in a single evaluation. RESULTS: The mean GH concentration during
      sleep was more often normal (n = 155) than the GH peak after provocative tests (n
      = 105) or the IGF-I concentration (n = 88). Prepubertal patients with a normal
      body mass index (BMI) had mean GH concentrations during sleep that correlated
      positively with height, growth rate, GH peak after provocative tests, and IGF-I
      (p < 0.0005 for all) and negatively with the difference between target and
      patient heights (p = 0.01) and BMI (p < 0.05). Pubertal patients with a normal
      BMI had a mean GH concentration during sleep that correlated positively with GH
      after provocative tests (p < 0.0001) and IGF-I (p < 0.005). Mean GH concentration
      during sleep and IGF-I concentration for boys primed with testosterone were more
      often normal (n = 23) than the GH peak after provocative tests (n = 14). All 9
      patients with pituitary stalk interruption had low IGF-I concentrations; 1
      patient had a normal GH peak after provocative test, and 2 patients had normal
      mean GH concentrations during sleep. CONCLUSIONS: Measuring the GH concentration
      during sleep and priming boys with pubertal delay can help to exclude idiopathic
      GH deficiency. Magnetic resonance imaging is needed to exclude anatomic
      abnormalities when GH and/or IGF-I concentrations are low.

PMID- 12792153
TI  - Low levels of the 150-kD insulin-like growth factor binding protein 3 ternary
      complex in patients with anorexia nervosa: effect of partial weight recovery.
AB  - BACKGROUND/AIM: In healthy adults, serum insulin-like growth factor I (IGF), IGF
      binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) form a 150-kD ternary
      complex under the control of growth hormone (GH). Circulating IGF-I half-life,
      bioavailability, and endocrine actions depend on the ternary complex formation.
      Despite GH hypersecretion, serum IGF-I, IGFBP-3, and ALS levels have all been
      reported to be low in patients with anorexia nervosa (AN), while the degree of
      ternary complex formation in AN is unknown. METHODS: Serum ALS and 150-kD ternary
      complex formation were measured in 6 women with AN at the time of diagnosis and
      after partial weight recovery and in 6 healthy age-matched women serving as
      controls. RESULTS: Patients with AN had low levels of ALS and IGFBP-3 contained
      in the 150-kD ternary complex and in the non-150-kD fraction. Following partial
      weight recovery, the 150-kD IGFBP-3 ternary complex was fully normalized, despite
      only partial normalization of serum GH and IGF-I levels. Patients with AN did not
      present with IGFBP-3 proteolysis different from controls. CONCLUSION: The present
      data indicate a pivotal role of the nutritional status in the regulation of each
      of the three components of the 150-kDa ternary IGFBP-3 complex and in the
      formation of the complex itself.

PMID- 12792154
TI  - Empty sella following spontaneous resolution of a pituitary macroadenoma.
AB  - BACKGROUND/AIM: Empty sella is a radiological finding characterized by the
      presence of arachnoid herniation into the sella, resulting in compression of the
      pituitary against the sella wall. The objective of this case presentation is to
      discuss secondary empty sella in a patient with spontaneous resolution of a
      pituitary macroadenoma. METHODS: A case of empty sella syndrome is presented.
      Static and dynamic testing was performed. Etiology, pituitary function, and
      imaging are discussed. RESULTS: A 69-year-old African-American woman was referred
      by her primary care physician for evaluation and treatment of 'hypothyroidisim'.
      Thyroid tests were performed because of muscle and joint tenderness and revealed
      low free thyroxine and normal thyroid-stimulating hormone levels. The diagnosis
      of secondary hypothyroidism was made, and magnetic resonance imaging (MRI) of the
      pituitary revealed an empty sella turcica. In retrospect, the patient had
      presented 11 years earlier with tinnitus, and an MRI of her auditory canals
      demonstrated an 'incidental' 1.5-cm pituitary tumor. No endocrine evaluation was
      done at that time, and neurosurgical follow-up of the pituitary tumor by serial
      MRIs demonstrated the genesis into empty sella. CONCLUSIONS: In our patient the
      natural history of her pituitary tumor was that it involuted and resulted in an
      empty sella. Although oftentimes speculated as a cause of empty sella, tumor
      involution has rarely been shown to be causative. In this instance, empty sella
      was associated with hypopituitarism. This case illustrates the importance of
      endocrine evaluation of patients with this radiological finding.

PMID- 12792155
TI  - Age-related changes in pharmacokinetics and pharmacodynamics of lerisetron in the
      rat: a population pharmacokinetic model.
AB  - BACKGROUND: The importance of studying the effects of age on the pharmacokinetics
      and pharmacodynamics of lerisetron - a new 5-hydroxytryptamine-3 (serotonin)
      receptor antagonist - comes from the facts that lerisetron will be administered
      to patients that are being treated with cytotoxic drugs and that the elderly
      frequently suffer from neoplastic diseases. OBJECTIVE: The present study was
      designed to explore the effects of age on the pharmacokinetics and
      pharmacodynamics of lerisetron by using an aged rat model. A mixed-effects
      population study was carried out in order to analyze the sparse data and to
      create covariate models which could be used to derive dosage recommendations.
      METHODS: Fischer 344 rats (n = 44) were divided into three groups, depending on
      their age: 5, 13, and 25 months. Blood samples were collected before
      administration of 200 micro g/kg of lerisetron for measurements of albumin,
      alpha(1)-acid glycoprotein, and unbound fraction of lerisetron. The lerisetron
      plasma concentrations were measured by high-performance liquid chromatography. A
      two-compartment model was fitted to the data using the nonlinear mixed-effects
      computer program WinNonMix. The population analysis was performed with the
      complete set of the collected data, and the potential sources of variability in
      the population parameters were investigated. Additionally, a pharmacodynamic
      study was performed. The effect of lerisetron (inhibition of the von Bezold
      Jarisch reflex) was evaluated in young, adult, and senescent Fischer 344 rats.
      RESULTS: The mean values of the individual Bayes estimates of the parameters
      showed a decrease in total clearance and distribution volume of the central
      compartment in old rats. The lerisetron free (unbound) fraction remained
      unchanged among the groups, and there were no significant differences in alpha(1)
      acid glycoprotein levels. The concentration-effect relationship was best
      described by a sigmoid E(max) model. Since the drug concentration in plasma at
      half-maximal effect (EC(50)) decreased in old rats, an increased sensitivity to
      the effect of lerisetron in old animals could be expected. CONCLUSION: Both
      pharmacokinetic changes (decreased volume of distribution and clearance and
      increased elimination half-life) and pharmacodynamic alterations (decrease in
      total and unbound EC(50)) may be responsible for the different responses to
      lerisetron observed in old rats.

PMID- 12792156
TI  - Variations in nutritional status of elderly men and women according to place of
      residence.
AB  - OBJECTIVE: The purpose of this study was to assess comprehensively the
      nutritional status of elderly individuals in institutions and to compare it with
      that of community based dwellers in an urban setting in Lebanon. METHODS:
      Participants included 100 elderly men and women (aged 65 years and older)
      selected randomly from four institutions who were based on sex and neighborhood
      with 100 free-living individuals. Subjects were mentally and physically capable
      of responding to an interview schedule. Their nutritional status was assessed by
      anthropometric measurements, dietary food intake for a 3-day period, and
      hematological and biochemical variables. Energy and macro- and micronutrient
      intakes were compared with the US recommended dietary allowances (RDA) or dietary
      reference intakes (DRI) as appropriate. RESULTS: Elderly living at home had
      significantly higher mean body mass index and waist circumference than those
      living in institutions. Although the total energy intake was comparable between
      the two groups, the elderly in the institutions consumed more fat and had lower
      intake of dietary fibers. Deficiencies (below 2/3rd RDA/DRI intakes) in zinc,
      magnesium, alpha-tocopherol, vitamins A and D, and pyridoxine were noted in both
      study groups with overall higher proportions observed among the institutionalized
      elderly. These were also anemic (42.5%) and had low levels of albumin (27.5%). In
      contrast, those living at home showed a higher prevalence of obesity and a lower
      calcium intake. Multivariate analysis controlling for a number of potential
      covariates did not change the results observed. CONCLUSIONS: The results of the
      present study showed a higher prevalence of obesity in those living at home and
      varying deficiencies by place of residence with no evidence that duration of
      institutionalization in itself being associated with poor nutritional status.
      Awareness of the risks associated with these deficiencies and excesses should
      address the lay and health professionals working in the community and
      institutions alike.

PMID- 12792157
TI  - Interaction between attention demanding motor and cognitive tasks and static
      postural stability.
AB  - BACKGROUND: Due to the often-reported decrease in postural stability in the
      elderly, it is important to understand factors that may contribute to reduced
      postural stability. It is possible that attention-demanding focal tasks performed
      concurrent with postural regulation influence postural stability. OBJECTIVE: This
      study utilized dual-task methodology to determine if motor or cognitive focal
      tasks interact with center of pressure (COP) excursion during static bipedal
      stance in healthy young and healthy elderly subjects (n = 18). METHODS: The
      cognitive task involved silently solving an orally-presented multi-step
      arithmetic problem over a 30-second period. The motor task was a 30-second
      bilateral static finger-thumb pinch task performed at 10% of maximal voluntary
      contraction with a pair of pinch-force transducers. Each focal task was performed
      separately, and in a condition in which both tasks were performed simultaneously.
      COP excursion was compared in quiet standing (no focal task) and during
      performance of the focal tasks with full vision and with vision occluded.
      RESULTS: Performance on the focal tasks was unaffected by increased postural
      demands during stance as compared to a seated baseline condition. This was the
      case for both age groups, and for the full vision and occluded vision conditions.
      Medio-lateral COP excursion was reduced over the quiet standing pretest condition
      when attentional focus was on the cognitive task, suggesting that COP was
      influenced centrally during cognition. In contrast, COP excursion increased over
      the quiet standing pretest condition when performing the motor focal task,
      suggesting a reduced ability to suppress sway when the motor system was
      concurrently occupied with a voluntary task that shared the same input-output
      resources. CONCLUSION: The ability to share attentional resources among focal and
      postural tasks was similar in healthy young and elderly subjects.

PMID- 12792158
TI  - Temporal surveillance of the humoral immunity against influenza vaccine in the
      elderly over 9 consecutive years.
AB  - BACKGROUND: The effect of age on declining immunity is well established, but its
      influence on humoral responses to influenza vaccines is still debated. OBJECTIVE:
      To compare prospectively the immunogenicity of an influenza vaccine in elderly
      and healthy control subjects and to search for correlations between this specific
      humoral protection and clinical and virological parameters. METHODS: A
      prospective study of the humoral response to influenza vaccine was conducted over
      9 consecutive years in the long-term care units of the Saint-Etienne University
      Hospital, France. Antibodies directed against the vaccinal strains in an
      inactivated trivalent vaccine were tested by radial haemolysis before and 1 month
      after 477 and 242 cumulative annual vaccinations in elderly people and in healthy
      controls, respectively. During the last 6 years of the study, clinical samples
      from patients with fever > or =38 degrees C were tested systematically for the
      diagnosis of an influenza infection. RESULTS: A significant rise in anti-A/H3N2
      antibody titres was observed in 49.3% of the elderly subjects and in 48.3% of the
      controls (not significant). The rises for the A/H1N1 and B strains were 31.4 and
      39.2% (p < 0.001) and 30.6 and 40.5 (p < 0.001), respectively. When control
      subjects under 31 years old were excluded, no significant difference was recorded
      for any strain. Only 3.9% of the vaccinated elderly experienced any clinical
      influenza infection as defined by fever >/=38 degrees C and virological proof.
      CONCLUSIONS: The humoral response to influenza immunization is not impaired in
      the elderly compared with middle-aged controls, and the incidence of febrile
      episodes due to influenza is low in this vaccinated elderly population. These
      findings provide further evidence supporting the recommendation for annual
      influenza vaccination in the elderly.

PMID- 12792159
TI  - Effects of regular walking on postural stability in the elderly.
AB  - BACKGROUND: Both age and lack of physical activity may be responsible for poor
      health and poor balance control. Conversely, physical activity may modulate
      postural control in elderly people. OBJECTIVE: An observational study was
      performed in older adults to explore whether walking on a regular basis might
      prove to be beneficial not only to the cardiovascular system but also to
      maintaining a good balance. METHODS: Twenty-two healthy older subjects walking on
      a regular basis (DW group) and 121 healthy control older subjects who did not
      walk regularly (NW group) were studied. The subjects included in the study were
      free from major gait and postural disorders. An instrumented force platform was
      used to measure the time-varying displacements of the center of pressure under
      eight static conditions and postural limit tests. An isometric test was performed
      to evaluate lower limb muscle strength, and a static two-point discrimination
      test evaluated the innervation density of the slowly adapting receptors of the
      sole of the first toe. RESULTS: The DW group had a significantly better (p <
      0.05) postural stability under static conditions than the NW group. There were no
      significant differences in postural limit tests and in two-point discrimination
      between the groups. The DW group had significantly higher values of ankle plantar
      flexor and knee extensor strengths, while there were no significant differences
      in ankle dorsiflexors and knee flexors. None of the DW group reported
      experiencing a fall during the previous 6 months compared with 16% in the NW
      group who reported at least two falls during the last half year. CONCLUSIONS:
      Walking on a regular basis in old age may have the potential to modulate
      stability. It was found that healthy older subjects, who walked on a regular
      basis since their retirement, have better postural control, especially in their
      static balance, than those who do not. The laboratory results were accompanied by
      the important finding that although older subjects who walk on a regular basis
      walked much more than nonwalkers, they did not suffer from falls.

PMID- 12792160
TI  - Impact of pneumococcal vaccination on morbidity and mortality of geriatric
      patients: a case-controlled study.
AB  - BACKGROUND: Infections due to Streptococcus pneumoniae are the major cause of
      adult community-acquired pneumonia, especially in elderly persons with chronic
      medical conditions. Despite their well-documented efficacy against bacteraemic
      disease and deaths in the elderly population, pneumococcal polysaccharide
      vaccines are still very much underused. OBJECTIVE: A retrospective, case
      controlled study was performed to investigate the impact of vaccination with a
      polysaccharide pneumococcal vaccine, together with other risk factors, on the
      incidence of pneumonia and deaths in patients in a long-stay geriatric hospital.
      METHODS: Subjects were 1,077 residents in a long-stay geriatric hospital in
      Vienna, Austria, including 359 patients diagnosed as having pneumonia during the
      period from July 1996 to October 1998 and 718 control subjects. Two controls
      resident in the hospital during the same time period were matched for each case
      according to demographic characteristics, chronic illness, and duration of stay
      in the geriatric ward. The vaccination status was established for all subjects. A
      logistic regression analysis was performed to assess the efficacy of vaccination
      and the impact of other cofactors on disease and death. RESULTS: In cases and
      controls, 514 (47.7%) had received a pneumococcal vaccine within 2 years prior to
      the study. There were no differences in demographic characteristics, underlying
      medical conditions, or duration of stay in the hospital between vaccinated and
      non-vaccinated patients. In patients diagnosed with pneumonia, 66% were
      unvaccinated. Logistic regression analysis showed that vaccination significantly
      decreased the risk of pneumonia (odds ratio 0.279; p < 0.0001). Of the cofactors
      tested, only gender (lower risk in males) and diabetes mellitus (higher risk) had
      any impact on disease risk and vaccine efficacy. There appeared to be a highly
      significant effect of vaccination, reducing the risk of all deaths (odds ratio
      0.269; p < 0.0001) and deaths due to pneumonia (odds ratio 0.331; p < 0.0001).
      CONCLUSION: This study showed that vaccination with a polysaccharide pneumococcal
      vaccine is effective in all groups of geriatric subjects and has a consequential
      value for health and well-being of elderly institutionalized patients.

PMID- 12792161
TI  - Age-correlated changes of the erythrocyte catalase activity in the Spanish
      population.
AB  - BACKGROUND: Oxygen free radical and reactive oxygen species are involved in many
      diseases and ageing. Scavening enzymes represent one of the several natural
      defence mechanisms against free radical induced damage. Catalase (CAT) is an
      enzyme that is involved in antioxidant defence. OBJECTIVE: In order to establish
      a comprehensive profile of the erythrocyte CAT activity during ageing, we
      investigated this activity in human erythrocytes from 2,827 apparently healthy
      Spanish subjects (1,388 males and 1,439 females). METHODS: We divided the
      subjects into twelve age groups (newborns and 1-3, 4-9, 10-19, 20-29, 30-39, 40
      49, 50-59, 60-69, 70-79, 80-89, and >90 years of age) to evaluate ageing changes.
      The CAT activity was measured in haemolysates by the method of Aebi (see text).
      RESULTS: No significant variations with respect to sex were detected, except for
      the 70- to 93-year age groups. In these elderly subjects, the CAT activity in
      males remained constant with no significant variations between age groups,
      whereas the CAT activity showed a significant increase in females. This fact is
      considered to be one of the outcomes of the greater longevity in females.
      Significant age-related modifications in erythrocyte CAT activity appeared in the
      group of newborns (p < 0.001), in the group 1-3 years of age (p < 0.025), and in
      the elderly groups: 70-79 years (p < 0.025) and 80-89 years (p < 0.05) of age.
      CONCLUSION: Our results confirm that the CAT activity in the Spanish population
      shows an interindividual variability and suggest that this variability may be
      due, at least in part, to the age of the individuals.

PMID- 12792163
TI  - Postprandial systolic blood pressure responses of older people in residential
      care: association with risk of falling.
AB  - BACKGROUND: The association between postprandial blood pressure, falls and
      medications is controversial. OBJECTIVE: To investigate cardiovascular responses
      to meals in elderly people together with clinical associations and therapeutic
      issues. METHODS: A cross-sectional observational study of 179 semi-independent
      older people (age 83.2 +/- 7.0 years) in residential care facilities was
      undertaken. Data on the frequency of falls, medical and medication history and
      measurement of blood pressure before and after a breakfast meal, and then after
      standing and walking after the meal were documented. RESULTS: Postprandial
      hypotension (>/=20 mm Hg fall in systolic blood pressure (SBP)) and low absolute
      SBP (</=115 mm Hg) were common after meals and exacerbated by standing. Risk
      factors for low postprandial SBP included use of selective serotonin reuptake
      inhibitors (OR = 4.3, CI 1.4-13.1, p = 0.006), antipsychotic medications (OR =
      5.2, CI 1.4-19.2, p = 0.007) and a history of smoking (OR = 4.7, CI 1.5-14.9, p =
      0.005). Antihypertensive therapy ameliorated the postprandial decline in blood
      pressure. The incidence of falls was increased only in the 10% of subjects with
      low postprandial SBP. CONCLUSIONS: Significant adverse cardiovascular change is
      common after meals in older people and a postprandial SBP of <115 mm Hg was
      associated with a history of falls. Selective serotonin reuptake inhibitors and
      antipsychotic medications were associated with low postprandial SBP, which may
      provide a mechanism for their association with falls. Hypertension was positively
      and antihypertensive therapy negatively associated with postprandial hypotension.

PMID- 12792162
TI  - Low serum albumin levels, confusion, and fecal incontinence: are these risk
      factors for pressure ulcers in mobility-impaired hospitalized adults?
AB  - BACKGROUND: Studies of risk factors for clinically significant pressure ulcers in
      the hospital have been limited by the small number of study subjects that develop
      pressure ulcers, resulting in contradictory findings regarding some risk factors.
      OBJECTIVE: To determine if three risk factors (low serum albumin level, fecal
      incontinence, and confusion) were significant risk factors when tested in a large
      data set. METHODS: The study design was a longitudinal cohort study using data
      collected as a component of a multi-site controlled clinical trial. The data were
      collected at 47 Veterans Affairs Hospitals. 2,771 subjects that required high
      levels of nursing care were identified to have mobility impairment. Their medical
      records were abstracted using a standard form to identify a large number of
      potential risk factors. The subsequent development of stage 2 or greater pressure
      ulcers was recorded for a maximum of 14 days after admission. RESULTS: 406
      patients (14.7%) subsequently developed at least one stage 2 or greater pressure
      ulcer over a 2-week period. In a multivariate model, the presence of low albumin
      levels (odds ratio OR = 1.40) and confusion (OR = 1.45) were both found to be
      statistically significant risk factors, while fecal incontinence was not. Having
      a Do Not Resuscitate (DNR) order was also a significant risk factor (OR = 1.55).
      Two other known risk factors also entered the model: being malnourished (OR =
      1.69) and requiring a urinary catheter (OR = 1.55). CONCLUSIONS: This study
      confirmed confusion and low albumin as pressure ulcer risk factors, but not fecal
      incontinence. A DNR order was found to be a new pressure ulcer risk factor not
      previously described in the literature.

PMID- 12792164
TI  - Self-rated life expectancy as a predictor of mortality: evidence from the HRS and
      AHEAD surveys.
AB  - BACKGROUND: An extensive literature has demonstrated that self-ratings of health
      predict mortality, even after controlling for more objective measures of health,
      health habits and sociodemographic characteristics. We examine the role of a
      related concept, self-rated life expectancy, in predicting mortality. OBJECTIVE:
      To assess whether self-rated life expectancy predicts mortality after controlling
      for measures of health, self-rated health, and sociodemographic characteristics.
      METHODS: Using data from the 1992 Health and Retirement Survey (HRS), the 1993
      Asset and Health Dynamics Among the Oldest Old (AHEAD) survey, and the second
      Tracker file (2.0), Cox proportional hazard models were estimated to assess
      whether self-rated life expectancy predicts mortality, after adjusting for self
      rated health and several potential confounders that might otherwise explain this
      relationship. The AHEAD sample included 2,102 men and 3,160 women. During the 2
      years of follow-up, 9% (n = 185) of the men died and 5% (n = 166) of the women
      died. The HRS sample was comprised of 4,090 men and 4,885 women. Four percent (n
      = 164) of the men died and 2% (n = 99) of the women died in the 3 years of follow
      up. RESULTS: In the older, AHEAD sample, both self-rated life expectancy (p <
      0.01) and self-rated health (p < 0.05) predicted mortality for both men and
      women, even when the two measures were included in the model together. In the
      younger, HRS sample, self-rated life expectancy was not significantly associated
      with mortality when self-rated health was included in the model. CONCLUSION: Our
      findings suggest that, although self-rated life expectancy and self-rated health
      may be conceptually related, they have independent empirical effects on
      mortality.

PMID- 12792168
TI  - The prognostic significance of changes in X-ray attenuation on CT in established
      cerebral infarcts.
AB  - BACKGROUND: X-ray hypoattenuation on computed tomography (CT) reflects the
      severity of ischaemic damage after stroke. However, the clinical syndrome and the
      effect of time influence the visibility of infarcts. This prospective study
      analyses whether the degree of hypoattenuation on CT at two time intervals after
      stroke has a predictive value for the clinical outcome. METHODS: 220 consecutive
      stroke patients were admitted within 24 h after onset with symptoms lasting more
      than 24 h. The study was restricted to 150 patients displaying an anterior
      circulation infarct or syndrome. All patients had CT scans without contrast
      enhancement on day 3 (+/-8 h) and day 10 (+/-8 h) after stroke onset. The degree
      of X-ray attenuation expressed in Hounsfield units was determined in the centre
      of the infarct area and compared to that in the corresponding zone of the
      contralateral hemisphere. The patients were divided into four groups according to
      their degree of disability at 3 months on the modified Rankin scale as follows: R
      0-1, R 2-3, R 4-5 and R 6. RESULTS: Patients in groups R 4-5 and R 6 had the most
      severe impairment on admission. The average decrease of X-ray attenuation on CT
      on day 3 was less in patients in group R 0-1, but was not different between the
      three other groups, while it was significantly correlated with the severity of
      the disability on day 10. CT X-ray attenuation increased between days 3 and 10 in
      group R 0-1, was unchanged in group R 2-3 and further decreased in groups R 4-5
      and R 6. CONCLUSION: The degree of X-ray attenuation on CT on day 3 allows us to
      distinguish those patients who will recover more or less completely from those
      with definite disability, while the CT findings on day 10 allow a more precise
      prediction of outcome. Increase of X-ray attenuation on day 10 is known as the
      fogging effect and appears to be a favourable prognostic factor. Fogging is
      generally considered to be due to macrophage invasion and proliferation of
      capillaries within the infarct area, but probably also represents partial
      restoration of some viable tissue.

PMID- 12792169
TI  - Cerebral magnetic resonance imaging within 6 hours of stroke onset: inter- and
      intra-observer reproducibility.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) provides valuable pathophysiological
      information during the very first hours of cerebral ischemia. However, the
      reliability of prime-time MRI in the setting of emergency care remains unknown.
      AIM: To evaluate the reproducibility between and within observers of the
      assessment of MRI scans in stroke patients. METHOD: We performed a MRI scan
      within 6 h of stroke onset, with time-of-flight (TOF), T2* gradient echo, FLAIR,
      diffusion- (DWI) and perfusion- (PWI) weighted images, in 17 consecutive
      patients. Four observers, blinded to the clinical history, separately performed a
      visual assessment of all scans, and repeated the assessment 2-8 days later. Two
      neuroradiologists made volumetric measures of diffusion and perfusion
      abnormalities using a semi-automatic technique 2 weeks after the 2nd visual
      assessment. We evaluated: (i) in the whole set of MRI scans, the quality of scans
      and their ability to identify primary hemorrhages on T2* gradient echo sequences;
      (ii) in patients with acute cerebral ischemia only, the inter- and intra-observer
      agreement for the presence of arterial occlusion and cerebral abnormalities on
      TOF sequences, and (iii) on DWI and PWI sequences, the relationship between
      visual and automatic assessments for the presence of a mismatch (defined as the
      difference between the perfusion and diffusion abnormalities) of >20%. Statistics
      used the kappa (kappa) method. RESULTS: The median delay between clinical onset
      and MRI was 285 min. Two patients had primary cerebral hemorrhages, 1 a post
      ictal deficit, and 14 cerebral ischemia. The quality of the scans was judged as
      appropriate for all scans in all sequences except for FLAIR. All observers
      identified the 2 patients with hemorrhages. The inter- and intra-observer
      reliability was substantial to excellent (kappa values ranging from 0.63 to 1.00)
      for all sequences. The agreement between visual and automatic assessments for the
      presence of a mismatch of >20% was excellent in all observers. CONCLUSION: The
      visual assessment of T2* gradient echo, TOF, diffusion and perfusion sequences at
      the acute stage of stroke is reproducible between and within observers. The
      visual assessment is as good as the volumetric assessment to detect a mismatch of
      >20%.

PMID- 12792170
TI  - Stroke on awakening: looking for a more rational management.
AB  - BACKGROUND AND PURPOSE: Stroke on awakening (SOA) is denied the benefits of
      thrombolytic therapy and is typically excluded from acute clinical trials on the
      grounds that the time of onset is unknown. In this study we compared the clinical
      characteristics of SOA and of stroke while awake (SWA), particularly in the
      subgroup of patients seen within a time frame of 6 h after stroke awareness.
      MATERIAL AND METHODS: Patients were included consecutively in the Stroke Data
      Bank of the Spanish Neurological Society (BADISEN) that records 365 different
      items, including vascular risk factors, neurological findings, stroke severity,
      aetiopathogenic diagnosis and neuroimaging data. RESULTS: A total of 1,248
      patients with acute cerebral infarction were included in the study, 301 (24.1%)
      with SOA and 947 (75.9%) with SWA. The peak time for stroke occurrence was
      between 6:01 a.m. and 12 noon, both in the whole stroke group and in each
      aetiopathogenic stroke subtype. Age, sex, stroke risk factors, stroke severity at
      admission, vital signs and stroke subtypes were not significantly different
      between SOA and SWA, neither in the group as a whole nor in the group of patients
      seen within 6 h of stroke recognition. Six hundred and fifty-four patients were
      seen within the potential 6-hour therapeutic window. In this group, the CT scan
      on admission was normal in 39.4% of SOA but the ultimate CT/MRI scan showed that
      46.2% of these had a territorial infarction (in SWA these same figures were 60.8
      and 67.7%, respectively). CONCLUSION: There are no relevant differences in the
      clinical, neuroimaging and aetiopathogenic characteristics of SOA and SWA. We
      should rely on new techniques such as DWI/PWI to indicate the most appropriate
      treatment in a more rational manner as nearly half of the patients with SOA seen
      early may benefit from them.

PMID- 12792171
TI  - Stroke: awareness of the signs, symptoms and risk factors--a population-based
      survey.
AB  - BACKGROUND: This article reports the findings from a population-based survey
      conducted to determine baseline knowledge regarding the signs, symptoms and risk
      factors of stroke. METHODS: Data were collected in Northern Ireland from 892
      adults using a self-completed questionnaire. RESULTS: In general, the results
      indicate that respondents appeared knowledgeable about the risk factors of stroke
      but their recognition of the warning signs was poor. In addition, approximately
      half of those surveyed would not contact the ambulance service in the case of a
      suspected stroke but instead would make initial contact with their general
      practitioner (41.5%) or family/relatives (2.3%). CONCLUSIONS: Given the
      importance of early hospital presentation for effective stroke rehabilitation,
      these findings are of particular concern in a community where the death rate from
      stroke is one of the highest in Europe. Future health education campaigns should
      provide accurate and appropriate information regarding the warning signs of
      stroke and highlight the importance of early hospital presentation.

PMID- 12792172
TI  - Stroke in an elderly population: incidence and impact on survival and daily
      function. The Italian Longitudinal Study on Aging.
AB  - BACKGROUND: Epidemiological data are essential to estimate the burden of stroke.
      We evaluated stroke incidence in older Italians and the effect of first-ever
      stroke on survival and activities of daily living (ADL). METHODS: The analysis
      was performed in the Italian Longitudinal Study on Aging (ILSA) sample,
      consisting of 5,632 individuals aged 65-84. The ILSA aims at major cardiovascular
      and neurological age-associated diseases. The baseline survey was performed in
      1992 to detect prevalent diseases. The longitudinal examination started on
      September 1995 aiming at incidence, function and survival. RESULTS: Complete
      follow-up data were achieved for 77% of the baseline stroke-free cohort (4,164
      persons; 50.9% males; mean age 74.5 +/- 5.7 years). Incidence for first-ever
      stroke was 9.51 (95% CI: 7.75-11.27) per 1,000 person years and 12.99 (95% CI:
      10.99-14.98) including recurrent stroke (total incidence). Crude mortality was
      49.2% among first stroke patients and 15% among persons without stroke. The first
      ever stroke mortality risk ratio, adjusted for demographics and comorbidity, was
      2.40 (95% CI: 1.62-3.54). In survivors, impairment of at least one ADL was
      present in 67.6% of first-ever stroke patients vs. 31.6% of individuals without
      stroke. The comorbidity-adjusted OR was 2.63 (95% CI: 1.20-5.78) in the total
      cohort, and 4.00 (95% CI: 1.39-11.46) in individuals without disability at
      baseline. CONCLUSIONS: The ILSA provides the first data on stroke incidence in
      Italy on a national basis. Overall, 153,000 new cases can be expected annually in
      the Italian elderly population. First-ever stroke still has a strong effect on
      survival and function of older persons.

PMID- 12792173
TI  - Noninvasive assessment of spontaneous baroreflex sensitivity and heart rate
      variability in patients with carotid stenosis.
AB  - BACKGROUND: Previous limited observations have suggested that atherosclerosis may
      affect the distensibility of the carotid sinus and then impair the baroreflex
      sensitivity (BRS). No studies have been done to compare the BRS and heart rate
      variability (HRV) in patients with carotid stenosis and normal controls. METHODS:
      A convenience-consecutive sample of 118 patients with transient ischemic attack
      or minor stroke 3 months to 1 year before (mean 6 months) who met the study
      criteria were referred to the neurovascular laboratory of the study hospital.
      Forty-three age-matched healthy adults were recruited as the normal controls. The
      inclusion criteria for participation were (1) no diabetes mellitus, (2) no
      history, symptoms or ECG signs of coronary artery disease or myocardial
      infarction, and (3) presence of carotid stenosis greater than or equal to 50%.
      The diagnosis of carotid stenosis was made using color-coded duplex ultrasound
      with published criteria. We categorized the patients into two groups: group 1 had
      moderate stenosis (50-75%) and group 2 had high-grade stenosis (75-99%).
      Instantaneous systolic blood pressure (SBP) and heart rate of all participants
      were assessed noninvasively using servo-controlled infrared finger
      plethysmography. The fluctuation in SBP as well as the interpulse interval (IPI)
      was divided into three components at specific frequency ranges by fast Fourier
      transform as high frequency (HF; 0.15-0.4 Hz), low frequency (LF; 0.04-0.15 Hz)
      and very low frequency (VLF; 0.004-0.04 Hz). The BRS was expressed as (1)
      transfer function with its magnitude in the HF and LF ranges, (2) BRS index
      alpha, and (3) regression coefficient by sequence analysis. The HRV was expressed
      as total power and power in the three frequency ranges (HF, LF and VLF). RESULTS:
      The final analysis included 99 patients (mean age 72 +/- 6 years, 79 male) and 43
      healthy controls (mean age 68 +/- 7 years, 30 male). Forty-three patients were
      classified as group 1 (stenosis 50-75%) and 56 as group 2 (stenosis 75-99%).
      There was no significant difference in the IPI between patients and controls (p
      value = 0.8637). We observed a significant decrease in all three HRV components
      (VLF, LF and HF) in the patients; however, there were no differences between the
      two patient groups with various degrees of stenosis. All the indices of BRS,
      including the magnitude of SBP-IPI transfer function at LF and HF, the computed
      BRS index alpha and the regression coefficient of sequence analysis, revealed
      similar results. Patients exhibited a significant reduction in the BRS (p <
      0.001) compared with controls, and no difference was found between the two groups
      of patients. CONCLUSIONS: Our study linked significant carotid stenosis to two
      important autonomic markers (BRS and HRV) that may have prognostic value for
      patients with cardiovascular events. Further prospective studies are needed to
      explore whether or not the decreased BRS and HRV can be predictors for poor
      cardiovascular prognosis, or even for shortened life span in general, in patients
      with significant carotid stenosis.

PMID- 12792174
TI  - Determination of cerebrovascular reactivity by means of FMRI signal changes in
      cerebral microangiopathy: a correlation with morphological abnormalities.
AB  - BACKGROUND AND PURPOSE: A reduced cerebrovascular reactivity (CR) is a risk
      factor of cerebrovascular disease. In this study, we implemented a protocol to
      assess CR by means of functional MRI (fMRI) using hyperventilation. SUBJECTS AND
      METHODS: In 5 patients with cerebral microangiopathy (CM/lacunar infarction and
      white matter degeneration), 6 healthy elderly subjects (age-matched control), and
      6 young healthy subjects, the CR in response to hyperventilation was evaluated by
      fMRI using gradient echo-planar Imaging. The percentage signal change normalized
      by end-tidal CO(2) value was measured in various brain regions. RESULTS: All
      subjects performed hyperventilation well without adverse reaction and significant
      gross motion. Patients with CM showed significant qualitative and quantitative
      differences (p < 0.05) as compared to controls. The volume of gray matter showing
      significant CR was significantly reduced in patients: by 40% in comparison to the
      age-matched elderly control group and by 60% when compared with the young
      controls. The CR impairment was most pronounced in the frontal cortices with a
      drastically reduced magnitude of the magnetic resonance (MR) signal change in the
      patients (-0.62 +/- 0.2% in patients versus -2.0 +/- 0.36% in age-matched
      controls, p < 0.0001). A strong relation was evident between the fMRI-based CR
      reduction in patients with CM and the individual severity of structural MR
      abnormalities (p = 0.002). CONCLUSION: This study demonstrates that fMRI-based
      signal changes in response to hyperventilation reliably reflect cerebral
      vasoreactivity. The protocol is feasible in healthy young and elderly controls
      and patients with CM. Quantitative and qualitative assessment of the signal
      decrease in the T(2)-weighted MR sequence and coregistration with individual
      anatomical data allow the generation of an individual cerebral vasoreactivity
      map. Future research will address the effect of CR reduction on
      neuropsychological parameters in patients with CM.

PMID- 12792175
TI  - Prospective study of Chlamydia pneumoniae IgG and IgA seropositivity and risk of
      incident ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Chlamydia pneumoniae infection or exposure to C.
      pneumoniae was implicated as a risk factor for ischemic stroke. Our aim was to
      evaluate prospectively the association between the presence of antibodies to C.
      pneumoniae (IgG and IgA) and the risk of incident ischemic stroke among patients
      with pre-existing vascular disease. METHODS: Sera were collected from 3,090
      coronary heart disease patients enrolled in a secondary prevention trial. We
      measured baseline antibodies (IgG and IgA) in the sera of patients who developed
      subsequent ischemic strokes (cases, n = 134) during follow-up (mean 8.2 years),
      and in 134 age- and gender-matched pairs without subsequent stroke or myocardial
      infarction. RESULTS: The crude relative odds (95%CI) of incident ischemic strokes
      in seropositive patients at baseline (>1.1 relative value units) were 1.29
      (95%CI, 0.69-2.47) for IgG and 1.31 (95% CI, 0.69-2.55) for IgA by matched-pair
      analyses, and 1.42 (95%CI, 0.69-2.98) for IgG and 1.57 (95%CI, 0.76-3.35) for IgA
      after adjustments for conventional risk factors and the inflammatory marker,
      soluble intercellular adhesion molecule-1. We explored the possibility that the
      risk of ischemic stroke may increase in parallel to increasing antibody titers,
      but did not demonstrate any significant association. CONCLUSIONS: Serological
      evidence for prior infection with C. pneumoniae did not emerge as an independent
      risk factor for incident ischemic stroke among patients at high risk due to pre
      existing vascular disease.

PMID- 12792176
TI  - Acute subdural hematoma caused by aneurysmal rupture: incidence and clinical
      features.

PMID- 12792178
TI  - Dorsal medullary infarction.

PMID- 12792177
TI  - Traumatic intracystic hemorrhage in a case with thalamo-mesencephalic 'expanding
      lacunae': an uncommon cause of sudden-onset neurological signs.

PMID- 12792180
TI  - Trade-offs in the assessment of aphasia in acute stroke.

PMID- 12792179
TI  - Paramedian pontine infarct secondary to basilar artery dissection.

PMID- 12792184
TI  - Using technology to advance the knowledge work of clinical nurse specialists:
      part 2: transforming data into information and knowledge.

PMID- 12792185
TI  - Malpractice prevention and technology expertise.

PMID- 12792186
TI  - Treatment of severe sepsis with Xigris: implications for the clinical nurse
      specialist.

PMID- 12792187
TI  - A clinical nurse specialist private practice in nursing.

PMID- 12792189
TI  - Regulatory credentialing of clinical nurse specialists.

PMID- 12792188
TI  - Interdisciplinary rounds: impact on patients, families, and staff.
AB  - Interdisciplinary rounds are a new care coordination strategy in several
      healthcare settings. This article describes the process used by clinical nurse
      specialists in one institution to broaden existing discharge planning rounds to
      interdisciplinary rounds. In addition, a survey queried advanced practice nurse
      subscribers to two listserves, the ANPACC and CNS-L, to determine how other
      institutions conducted interdisciplinary rounds, including structure, membership,
      and leadership. As a result of the changed focus in rounds, the target
      institution noted greater participation by all disciplines in achieving patient
      and family outcomes, increased early recognition of patients at risk, and
      improved communication among members of the healthcare team. These findings were
      supported by participants in the Internet survey. It was determined that
      interdisciplinary rounds are a valuable mechanism for improved patient outcomes
      and increased staff professionalism.

PMID- 12792190
TI  - Clinical nurse specialist profile: an interview with Christine Carson Filipovich.

PMID- 12792191
TI  - Walter Salles' Central Station: a film of light and hope.

PMID- 12792192
TI  - Interactive data collection: benefits of integrating new media into pediatric
      research.
AB  - Despite the prevalence of children's computerized games for recreational and
      educational purposes, the use of interactive technology to obtain pediatric
      research data remains underexplored. This article describes the development of
      laptop interactive data collection (IDC) software for a children's health
      intervention study. The IDC integrates computer technology, children's
      developmental needs, and quantitative research methods that are engaging for
      school-age children as well as reliable and efficient for the pediatric health
      researcher. Using this methodology, researchers can address common problems such
      as maintaining a child's attention throughout an assessment session while
      potentially increasing their response rate and reducing missing data rates. The
      IDC also promises to produce more reliable data by eliminating the need for
      manual double entry of data and reducing much of the time and costs associated
      with data cleaning and management. Development and design considerations and
      recommendations for further use are discussed.

PMID- 12792193
TI  - A guide to assist nurse practitioners with standardized nursing language.
AB  - The purpose of this project was to develop a guide to support use of the Omaha
      System in primary care. The Omaha System is a community practice-based
      standardized nursing language developed by the Visiting Nurses Association (VNA)
      of Omaha, NE. Nurse practitioners at a primary care faculty practice clinic began
      using the Omaha System to describe more completely the advanced nursing care
      provided to clients, beyond ICD-9 and CPT codes. After 9 months of data
      collection, key faculty members convened to analyze the data and discuss issues
      in coding and interpretation. To simplify use of the system and facilitate
      orientation of new faculty, this group devised a Primary Care Guide for the Omaha
      System. High-frequency problems and interventions were identified. Definitions of
      the intervention categories were reviewed, and targets appropriate for the
      primary care environment were recorded. The result was a concise, user-friendly
      guide to assist the primary care nurse practitioner in the use of standardized
      nursing language.

PMID- 12792194
TI  - Online cancer support groups: a review of the research literature.
AB  - This article explores current research on online cancer support groups. A review
      of the literature revealed 9 research articles (describing 10 research studies)
      that focused on computer-mediated or Internet cancer support groups. The
      researchers in 9 of the 10 studies concluded that online cancer support groups
      helped people cope more effectively with their disease. Most of the research
      studies had small sample sizes. Six of the 10 studies did not include men, and
      six focused on Caucasian women with breast cancer. Information seeking/giving was
      prevalent in the online groups. Gender differences, negative psychological
      effects, and barriers to using online groups were identified. The few studies
      that were found in the literature suffered from a lack of experimental design,
      small and homogenous samples, and lack of outcome measures, thereby limiting
      applicability of results.

PMID- 12792195
TI  - Graduate students' experiences in web site development: a project assignment for
      nursing informatics class.
AB  - As healthcare delivery systems' requirements change, nurses will not only have to
      process and communicate more information, but the nature and types of this
      information as well as the communication methods will also dramatically change.
      Nurses must comprehend that information technology is the key to these changes.
      Korean nurses and nursing students need to enhance their computer technology
      knowledge and skills as the Korean health delivery system rapidly embraces
      technological innovations. Yonsei University College of Nursing in Seoul, Korea
      has the longest history in nursing education and the first graduate nursing
      programs in Korea. It offered its first nursing informatics (NI) class in 1998,
      making it one of the first informatics programs in Korean nursing education. The
      purposes of this project were to develop nursing informatics coursework that
      enabled students to build skills in developing Web sites, and to measure the
      effect of the coursework in terms of the students' satisfaction and their
      confidence level. The author believes that this experience could be a helpful
      model for an international audience, although this is not an innovative project
      for some more advanced countries.

PMID- 12792198
TI  - SPAM: coming soon to an E-mail box near you.

PMID- 12792196
TI  - Applying ergonomics to nurse computer workstations: review and recommendations.
AB  - Nursing is associated with high rates of musculoskeletal disorders from patient
      handling, and nurses are at high risk for developing cumulative trauma disorders,
      which can result from computer usage. Although there are many benefits to using
      computers in the workplace, nurses need to incorporate ergonomic factors into
      work settings to promote safe workplace environments. This article reviews recent
      literature about computer workstation ergonomics, discusses related policies, and
      makes recommendations about computer workstation design and related research in
      nursing workplace settings.

PMID- 12792199
TI  - Case in point: a trial of two anti-SPAM software products.

PMID- 12792200
TI  - Taking a proactive approach to managing SPAM.

PMID- 12792201
TI  - Gateway solutions for SPAM.

PMID- 12792202
TI  - Is legislation the solution?

PMID- 12792205
TI  - What price progress?

PMID- 12792203
TI  - Case in point: SPAM is in the eye of the beholder--my adventures in recruiting on
      the internet.

PMID- 12792206
TI  - Abnormal hematologic profiles in elite cross-country skiers: blood doping or?
AB  - OBJECTIVE: There is widespread public concern about fairness in sports. Blood
      doping undermines fairness and places athletes' health at risk. The purpose of
      this study was to examine the prevalence of abnormal hematologic profiles in
      elite cross-country skiers, which may indicate a high probability of blood
      doping. SETTING AND PARTICIPANTS: Samples were obtained as part of routine
      International Ski Federation blood testing procedures from participants at the
      World Ski Championships. Sixty-eight percent of all skiers and 92% of those
      finishing in the top 10 places were tested. MAIN OUTCOME MEASURES: Using flow
      cytometry, we analyzed erythrocyte and reticulocyte indices. Reference values
      were from the 1989 Nordic Ski World Championships data set and the International
      Olympic Committee Erythropoietin 2000 project. RESULTS: Of the skiers tested and
      finishing within the top 50 places in the competitions, 17% had "highly abnormal"
      hematologic profiles, 19% had "abnormal" values, and 64% were normal. Fifty
      percent of medal winners and 33% of those finishing from 4th to 10th place had
      highly abnormal hematologic profiles. In contrast, only 3% of skiers finishing
      from 41st to 50th place had highly abnormal values. CONCLUSIONS: These data
      suggest that blood doping is both prevalent and effective in cross-country ski
      racing, and current testing programs for blood doping are ineffective. It is
      unlikely that blood doping is less common in other endurance sports.
      Ramifications of doping affect not only elite athletes who may feel compelled to
      risk their health but also the general population, particularly young people.

PMID- 12792207
TI  - Effects of intermittent exposure to hyperbaric oxygen for the treatment of an
      acute soft tissue injury.
AB  - OBJECTIVE: To assess the hypothesis that subjects exposed to intermittent
      hyperbaric oxygen treatments would recover from signs and symptoms indicative of
      delayed-onset muscle soreness faster than subjects exposed to normoxic air.
      DESIGN: Randomized, double-blinded study with a 4-day treatment protocol.
      SETTING: University-based sports medicine clinic. PARTICIPANTS: Sixteen sedentary
      female university students. INTERVENTIONS: All subjects performed 300 maximal
      voluntary eccentric contractions (30 sets of 10 repetitions per minute) of their
      nondominant leg (110 to 35 degrees of knee flexion) at a slow speed (30 degrees
      per second) on a dynamometer to elicit muscle damage and injury. Hyperbaric
      oxygen treatments consisted of 100% oxygen for 60 minutes at 2.0 atmospheres
      absolute (ATA), while the control group received 21% oxygen at 1.2 ATA for the
      same amount of time. Both groups received treatment immediately after the
      induction of delayed-onset muscle soreness and each day thereafter for a period
      of 4 days (day 1 postexercise through day 4 postexercise). MAIN OUTCOME MEASURES:
      Dependent variables (perceived muscle soreness, isokinetic strength, quadriceps
      circumference, creatine kinase, and malondialdehyde) were assessed at baseline
      (preexercise, day 0), 4 hours postexercise (day 1), 24 hours postexercise (day
      2), 48 hours postexercise (day 3), and 72 hours postexercise (day 4). Magnetic
      resonance images (T2 relaxation time/short tip inversion recovery) were assessed
      at baseline (day 0), 24 hours postexercise (day 3), and 72 hours postexercise
      (day 5). RESULTS: Repeated-measures analysis of variance was performed on all of
      the dependent variables to assess differences between treatment and control
      groups. Analyses revealed no significant differences between groups for treatment
      effects for any of the dependent variables (pain, strength, quadriceps
      circumference, creatine kinase, malondialdehyde, or magnetic resonance images).
      CONCLUSIONS: The findings of this study suggest that hyperbaric oxygen therapy is
      not effective in the treatment of exercise-induced muscle injury as indicated by
      the markers evaluated.

PMID- 12792208
TI  - Agreement between magnetic resonance imaging and arthroscopic evaluation of the
      shoulder joint in primary anterior dislocation of the shoulder.
AB  - OBJECTIVE: To determine the effectiveness of magnetic resonance imaging in
      identifying shoulder pathology in patients with primary traumatic dislocation of
      the shoulder and to compare these findings with findings at the time of
      arthroscopic surgery. DESIGN: Correlation between arthroscopy and magnetic
      resonance imaging. PATIENTS: Sixteen patients, aged 18 to 30 years, who were
      randomized to the surgical arm of a study comparing the effectiveness of
      immediate arthroscopic surgery with immobilization and rehabilitation for primary
      traumatic anterior dislocation of the shoulder, were included in this study.
      INTERVENTIONS: Each patient underwent magnetic resonance imaging and a videotaped
      "tour" of the shoulder prior to any surgical intervention. MAIN OUTCOME MEASURE:
      Magnetic resonance scans and videotapes were reviewed for the presence or absence
      of abnormalities in 8 features of the shoulder, and concordant and discordant
      findings were evaluated. RESULTS: There was moderate correlation for superior
      labral lesions (kappa = 0.60) and fair agreement for rotator cuff tear (kappa =
      0.355). When the joint capsule was assessed, there was only fair agreement for
      both the presence of an abnormality (kappa = 0.310) and redundancy and tear
      (kappa = 0.394). Both methods were sensitive for the detection of Hill-Sachs
      lesions (kappa = 1.0), although there was only moderate agreement (kappa = 0.44)
      on estimation of size. There was perfect agreement for the detection of Bankart
      lesions or equivalent capsulolabral disruption (kappa = 1.0). CONCLUSIONS:
      Magnetic resonance imaging can be considered a valuable tool for the detection of
      Hill-Sachs and Bankart lesions associated with primary traumatic anterior
      dislocations of the shoulder. Its ability to detect other pathologic lesions,
      however, is limited.

PMID- 12792209
TI  - Hip joint pathology: clinical presentation and correlation between magnetic
      resonance arthrography, ultrasound, and arthroscopic findings in 25 consecutive
      cases.
AB  - BACKGROUND: The hip joint is becoming increasingly recognized as a source of
      groin pain and, in the authors' experience, buttock and low back pain.
      OBJECTIVES: To determine the range of pathologic diagnoses, clinical
      presentation, and the correlation between magnetic resonance arthrographic,
      ultrasonographic, and arthroscopic findings in the hip joint. METHODS: We
      prospectively studied 25 consecutive hip arthroscopies to determine the range of
      pathologic diagnoses, clinical presentation, and the correlation between magnetic
      resonance arthrographic, ultrasonographic, and arthroscopic findings. RESULTS:
      All of the hips arthroscoped had pathology. Back pain and hip pain were the 2
      most common presentations. The only consistently positive clinical test result
      was a restricted and painful hip quadrant compared with the contralateral hip. Of
      the 17 patients whose flexion, abduction, external rotation (FABER) test results
      were reported at the time of examination, 15 (88%) were positive, and 2 (12%)
      negative. Plain radiographs were normal in all patients. All but 1 patient
      underwent magnetic resonance arthrography. Although specificity of 100% was
      achieved in our study, the sensitivity was significantly lower, with a relatively
      high number of false negatives. Hip arthroscopy proved the definitive diagnostic
      procedure for intraarticular pathology. CONCLUSIONS: Hip pathology, particularly
      labral pathology, may be more common than has been previously recognized. In
      those patients with chronic groin and low back pain, a high index of suspicion
      should be maintained. Clinical signs of a painful, restricted hip quadrant and a
      positive FABER test result should suggest magnetic resonance arthrography in the
      first instance, but a negative magnetic resonance image should not preclude hip
      arthroscopy if there is high clinical suspicion of hip joint pathology.

PMID- 12792210
TI  - Incidence of injury and physical performance adaptations during military
      training.
AB  - OBJECTIVE: Strenuous physical activity, such as military training, is known to
      demand a high degree of physical performance and to cause overuse injuries.
      However, the exact relation between injury incidence and physical fitness level
      and the influence of military training on measures of functional performance,
      such as intermittent endurance capacity and maximal jump performance, are not
      fully described. METHODS: A total of 330 military conscripts were prospectively
      followed during military basic training. They were divided into 4 self-assessed
      physical fitness level groups (well trained, trained, less trained, and
      untrained) and underwent physical performance tests together with registration of
      injury incidence. RESULTS: Twelve weeks of military basic training was found to
      result in an overall injury rate of 28%, with an inverse relation between
      physical fitness level and incidence of overuse injury (P < 0.0001). Furthermore
      a fourfold higher injury rate was observed in the previously untrained soldiers
      compared with the well-trained soldiers. An increase in intermittent endurance
      capacity (20-m intermittent shuttle run test) was seen in all groups, (13 to 62%,
      P < 0.05), whereas only the previously untrained group of soldiers improved in
      aerobic capacity (8 and 16%, P < 0.05; maximal oxygen uptake and Coopers 12
      minute running test). Maximal jump performance, both with and without backpack
      loading (15 kg), decreased (5 to 13%, P < 0.05) in 93% of the soldiers despite
      weight loss. CONCLUSIONS: Military basic training has a positive effect on
      intermittent endurance capacity but a detrimental effect on jump performance.
      Furthermore, low levels of physical fitness are strongly associated with
      proneness toward overuse injury development in soldiers going through intense
      training.

PMID- 12792211
TI  - Exposure to diagnostic ionizing radiation in sports medicine: assessing and
      monitoring the risk.
AB  - OBJECTIVE: To understand the estimation of both the effective dose and the risk
      estimate associated with diagnostic ionizing radiation in sports medicine and to
      appreciate strategies by which this radiation exposure may be minimized. DESIGN:
      Observational study. SETTING: Sports medicine practice. PATIENTS: A theoretical
      patient, athlete X (male, aged 20-29 years, 80 kg), was used to illustrate how
      the effective dose and the corresponding risk estimate are calculated for various
      common sports medicine investigations. Doses and risk estimates for female and
      pediatric athletes also are discussed. MAIN OUTCOME MEASURES: The effective dose
      and corresponding risk estimate associated with common sports medicine
      investigations. RESULTS: Computed tomography and radiographic examinations of the
      extremities have significantly lower effective doses than investigations about
      the trunk region. Bone scanning and computed tomography have a significantly
      higher effective dose than radiography. The risk estimates associated with the
      low doses used in diagnostic ionizing radiation procedures are extrapolated from
      epidemiologic studies on exposures to high doses of radiation, and several
      uncertainties exist in this estimation. Notwithstanding this, the responsible
      clinician should be aware of both the effective doses and the risk estimates that
      are associated with the more common investigations. The principles of
      justification and optimization for these investigations will help guide
      clinicians to reduce radiation exposure without compromising the management of
      their patients. CONCLUSIONS: Certain investigations have a greater effective dose
      and risk estimate than others. Elite athletes may potentially undergo numerous
      investigations in their career. An athlete radiation record may be useful to
      better manage this exposure.

PMID- 12792212
TI  - Change in serum sodium concentration during a cold weather ultradistance race.
AB  - OBJECTIVE: To investigate change in serum sodium concentration and its potential
      causes during a cold weather ultradistance race. DESIGN: Descriptive research.
      SETTING: A 100-mile (161-km) race over a snow-packed course in the Alaskan
      wilderness. Athletes competed in 1 of 3 divisions: foot, bike, or ski.
      PARTICIPANTS: Twenty athletes (11 runners, 6 cyclists, 3 skiers) volunteered for
      the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects were weighed and
      had blood drawn for hematocrit, serum sodium, serum aldosterone, and plasma
      arginine vasopressin concentrations pre- and postrace. Fluid and sodium intake
      were determined by race dietary analysis. RESULTS: Serum sodium concentration
      decreased significantly prerace (140.8 +/- 1.2 mmol/L) to postrace (138.4 +/- 2.2
      mmol/L), although no athletes were classified as hyponatremic. Mean weight loss
      was significant during the race (-1.2 kg), although 1 athlete maintained his
      weight, and 3 athletes gained small amounts of weight (0.2 kg, 0.2 kg, and 0.5
      kg, respectively). Hematocrit decreased significantly prerace (42.2 +/- 3.5) to
      postrace (40.3 +/- 4.1). Plasma arginine vasopressin and serum aldosterone
      increased significantly during the race (2.6 +/- 0.7 to 6.0 +/- 4.6 pg/mL and 5.1
      +/- 2.6 to 40.8 +/- 25.1 ng/dL, respectively). Fluid consumption was 300 +/- 100
      mL/h, and sodium intake was 310 +/- 187 mg/h. CONCLUSIONS: Decreased serum sodium
      concentration after a cold weather ultradistance race was due to fluid overload
      caused by excessive fluid consumption. Current recommendations that ultradistance
      athletes consume 500 to 1000 mL/h may be too high for athletes competing in the
      extreme cold.

PMID- 12792213
TI  - Therapeutic exercise and orthopedic manual therapy for impingement syndrome: a
      systematic review.
AB  - OBJECTIVE: To review randomized controlled trials evaluating the effectiveness of
      therapeutic exercise and orthopedic manual therapy for the treatment of
      impingement syndrome. DATA SOURCE: Reports up to October 2002 were located from
      MEDLINE, the Cochrane Database of Systematic Reviews, the Physiotherapy Evidence
      Database (PEDro), the TRIP database, and the Cumulative Index to Nursing & Allied
      Health Literature (CINAHL) using "shoulder" and "clinical trial"/"randomized
      controlled trial" as search terms. STUDY SELECTION: Studies were included if (1)
      they were a randomized controlled trial; (2) they were related to impingement
      syndrome, rotator cuff tendinitis, or bursitis; (3) one of the treatments
      included therapeutic exercise or manual therapy. DATA EXTRACTION: Two independent
      observers reviewed the methodological quality of the studies using an assessment
      tool developed by the Cochrane Musculoskeletal Injuries Group. Differences were
      resolved by consensus. DATA SYNTHESIS: Seven trials met our inclusion criteria.
      After consensus, the mean methodological score for all studies was 13.9 +/- 2.4
      (of 24). Four studies of 7, including the 3 trials with the best methodological
      score (67%), suggested some benefit of therapeutic exercise or manual therapy
      compared with other treatments such as acromioplasty, placebo, or no
      intervention. CONCLUSIONS: There is limited evidence to support the efficacy of
      therapeutic exercise and manual therapy to treat impingement syndrome. More
      methodologically sound studies are needed to further evaluate these
      interventions.

PMID- 12792214
TI  - Vasospasm-induced stroke in a varsity athlete secondary to ephedrine ingestion.

PMID- 12792215
TI  - Severe aortic stenosis in a professional football player.

PMID- 12792217
TI  - Rupture of latissimus dorsi in an athlete.

PMID- 12792218
TI  - Do the numbers add up?

PMID- 12792219
TI  - Challenges in IBD Research: updating the scientific agendas.

PMID- 12792220
TI  - Evidence of active cytomegalovirus infection and increased production of IL-6 in
      tissue specimens obtained from patients with inflammatory bowel diseases.
AB  - Recent reports have focused interest on human cytomegalovirus (HCMV) in
      inflammatory bowel diseases (IBD). Our aim in this study was to examine the
      frequency of HCMV-infected intestinal cells in tissue sections obtained from
      patients with IBD, and to investigate if HCMV-infected intestinal cells produce
      the proinflammatory cytokine IL-6. We studied intestinal tissue sections from 13
      patients with ulcerative colitis, 10 with Crohn's disease, 10 cancer patients
      without intestinal inflammation, and 10 samples from HCMV-infected AIDS patients.
      HCMV-DNA was detected by in situ hybridization in sections obtained from 12/13
      patients with ulcerative colitis, in 10 with Crohn's disease, in 10/10 samples
      from HCMV-infected AIDS patients, but not in any of the 10 samples that were
      obtained from uninflamed tissues. HCMV-specific antigens were detected in samples
      from all HCMV-infected AIDS patients, in 11/13 sections from patients with
      ulcerative colitis, in 10/10 samples from patients with Crohn's disease, but not
      in sections from uninflamed tissues. Cells were double positive for an HCMV early
      antigen and IL-6 in 10/13 sections from patients with ulcerative colitis, in all
      patients with Crohn's disease, and in 4/10 samples from AIDS patients. In
      conclusion, these results suggest that active HCMV infection in the intestine is
      very frequent in patients with IBD, and may contribute to the inflammatory
      process through an increased production of IL-6.

PMID- 12792222
TI  - Long-term results of ileal pouch-anal anastomosis in Crohn's disease.
AB  - The unexpected diagnosis of Crohn's disease (CD) after restorative
      proctocolectomy is a relatively frequent occurrence. We report a retrospective
      analysis of the long-term development of patients with an ileal pouch-anal
      anastomosis (IPAA) in whom the definitive anatomopathological diagnosis was CD,
      and compare their development with that of patients in whom the diagnosis of
      ulcerative colitis (UC) was confirmed. We reviewed the clinical data of 112
      patients with an IPAA. The definitive diagnosis was CD in 12, and UC in the rest.
      The mean follow-up period was 76 months (range 12 to 192). We analyzed and
      compared the epidemiologic and clinical data, postoperative complications,
      functional results, anxiety, and quality of life in the two groups. Postoperative
      morbidity and the degree of satisfaction were similar in the two groups. The test
      showed a lower level of anxiety and higher quality of life in patients with CD.
      Of all the functional parameters studied, only urgency of defecation presented a
      higher risk in the CD group (HR: 4.13, CI: 1.41-12.04, p = 0.027). Despite the
      fact that a diagnosis of CD is currently considered a contraindication for an
      IPAA, some patients with secondary diagnosis of CD have good functional outcome
      and quality of life after restorative proctocolectomy. Closure of the temporary
      ileostomy may be justified in these patients.

PMID- 12792221
TI  - Increased expression of HIP/PAP and regenerating gene III in human inflammatory
      bowel disease and a murine bacterial reconstitution model.
AB  - Although microorganisms play a role in gut inflammation, it remains uncertain
      which epithelial genes are expressed in response to luminal flora and whether
      these molecules are also involved in pathologic mucosal inflammation. Germ-free
      mice were orally challenged with a bacterial suspension prepared from
      conventionally housed mice (bacterial reconstitution). Thereafter, the
      differential gene expression in gut epithelial cells was identified by
      differential display. The expression of the identified genes was also examined in
      dextran sulfate sodium (DSS)-induced colitis and human inflammatory bowel disease
      (IBD) epithelial cells. Regenerating gene III (Reg III) was strongly induced in
      gut epithelial cells following bacterial reconstitution, as well as in the
      colitis initiated by DSS. The mRNA expression of hepatocarcinoma-intestine
      pancreas/pancreatic associated protein (HIP/PAP), a human counterpart of Reg III,
      was enhanced in colonic epithelial cells of patients with IBD. Reg III mRNA
      expression was localized in the epithelial cells including goblet cells and
      columnar cells in mice; on the other hand, HIP/PAP-expressing cells were
      correlated with Paneth cell metaplasia in human colon. Epithelial expression of
      Reg III or HIP/PAP was induced under mucosal inflammation initiated by exposure
      to commensal bacteria or DSS as well as inflamed IBD colon.

PMID- 12792223
TI  - A lupus-like syndrome associated with infliximab therapy.
AB  - Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha
      (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's
      disease. We report in detail an unusual adverse reaction to infliximab therapy, a
      drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid
      dependent Crohn's colitis, successfully managed with maintenance infliximab
      infusions and methotrexate, developed a lupus-like syndrome eight months after
      her initial infusion. This was characterized by inflammatory arthritis and an
      urticarial and papulosquamous rash and was accompanied by high titers of
      antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and
      by reduced levels of the C4 component of complement. After discontinuance of
      infliximab infusions and treatment of symptoms with intermittent courses of
      prednisone, the patient's arthritis progressively improved, with accompanying
      decrements in autoantibody titers. One year later, she has minimal joint
      discomfort and no rash or gastrointestinal symptoms despite also discontinuing
      prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome
      that is reversible upon discontinuing this agent. These findings support recent
      evidence identifying TNF-alpha as an inhibitor of autoantibody formation.

PMID- 12792224
TI  - Nitric oxide in inflammatory bowel disease.
AB  - Nitric oxide (NO) is a pleiotropic free radical messenger molecule. There is a
      large body of evidence that the inducible form of the NO synthase enzyme (iNOS)
      that is responsible for high-output production of NO from l-arginine is up
      regulated in various forms of mucosal inflammation. Consistent with this,
      multiple detection strategies have demonstrated that iNOS expression, enzymatic
      activity, and NO production are increased in human inflammatory bowel disease
      tissues. There is also evidence that the level of iNOS-derived NO correlates well
      with disease activity in ulcerative colitis, while for Crohn's disease, the
      results are more variable. A substantial number of animal studies have assessed
      the role of inducible NO production. While the majority of studies have shown
      improvement in experimental inflammatory bowel disease with iNOS inhibition,
      there are also a significant number of reports of exacerbation of disease with
      inhibitors. Similarly, studies using iNOS-deficient mice in colitis models have
      shown improvement, worsening, or no effect on disease. The authors suggest that
      additional studies to assess the role of the competing biochemical pathway,
      namely the conversion of l-arginine to polyamines via the actions of arginase and
      ornithine decarboxylase, may provide important new insights into understanding
      the regulation of mucosal inflammation and inflammatory bowel disease.

PMID- 12792225
TI  - IBD International Genetics Consortium: international cooperation making sense of
      complex disease.
AB  - The Inflammatory Bowel Disease International Genetic Consortium was formed in
      Oxford in 1997. Since then it has grown to include twelve groups from around the
      world that are each actively involved in identifying the genes that are involved
      in susceptibility to IBD. The approach of the IBDIGC is to attempt to overcome
      one of the major issues in complex disease analysis-that of obtaining sufficient
      power to analyze successfully the inheritance of IBD-by collaboratively studying
      large numbers of well documented families with multiple affected individuals.
      This strategy has been marked by considerable success with the publication of a
      paper authored by the IBDIGC substantiating the localization of IBD1 to
      chromosome 16. This publication served to encourage researchers and eventually
      resulted in the identification by several groups simultaneously of risk alleles
      in the NOD2 gene that cosegregate with disease. The IBDIGC provides a model for
      studies in complex disease genetics, showing that research groups both large and
      small can participate equally in complex disease gene identification through the
      formation of large international consortia.

PMID- 12792226
TI  - Is there still a role for cyclosporine in the treatment of inflammatory bowel
      disease? Pro argument.

PMID- 12792227
TI  - Is there still a role for cyclosporine in the treatment of inflammatory bowel
      disease? Con argument.

PMID- 12792229
TI  - Ten common errors in the management of inflammatory bowel disease.

PMID- 12792230
TI  - Current management of purpura fulminans: a multicenter study.
AB  - Seven burn centers performed a 10-yr retrospective chart review of patients
      diagnosed with purpura fulminans. Patient demographics, etiology, presentation,
      medical and surgical treatment, and outcome were reviewed. A total of 70 patients
      were identified. Mean patient age was 13 yr. Neisseria meningitidis was the most
      common etiologic agent in infants and adolescents whereas Streptococcus commonly
      afflicted the adult population. Acute management consisted of antibiotic
      administration, volume resuscitation, ventilatory and inotropic support, with
      occasional use of corticosteroids (38%) and protein C replacement (9%). Full
      thickness skin and soft-tissue necrosis was extensive, requiring skin grafting
      and amputations in 90% of the patients. One fourth of the patients required
      amputations of all extremities. Fasciotomies when performed early appeared to
      limit the level of amputation in 6 of 14 patients. Therefore, fasciotomies during
      the initial management of these patients may reduce the depth of soft-tissue
      involvement and the extent of amputations.

PMID- 12792231
TI  - Burn center management of necrotizing fasciitis.
AB  - Necrotizing fasciitis is a rapidly progressive soft-tissue infection associated
      with significant morbidity and mortality. Necrotizing fasciitis is similar to
      invasive burn wound infection in that diagnosis requires histologic examination
      of affected tissue and treatment requires aggressive surgical debridement
      followed by skin autograft. Transfer to a burn center facilitates the management
      of necrotizing fasciitis, where requisite surgical and nursing expertise is
      available. We reviewed the experience of one burn center in the management of
      necrotizing fasciitis over a 5-year period. Ten patients were transferred to the
      burn center from other medical facilities for care, arriving a mean of 8.9 days
      after initial hospital admission. The diagnosis was made by a surgical service or
      consultation before transfer in all cases; initial admission to a medical rather
      than a surgical service delayed surgery in five cases. All patients had surgical
      debridement before transfer but required a mean of 5.1 additional operations at
      the burn center. Although the mean extent of involvement was 14.8% body surface
      area, the mean length of burn center stay was 34.9 days. Complications were
      frequent, including pulmonary failure requiring mechanical ventilation (n = 6),
      renal insufficiency or failure (n = 5), hypotension requiring pressers (n = 4),
      deep venous thrombosis (n = 3), and pulmonary emboli (n = 1). Overall mortality
      was 2 of 10 patients (20%). Both fatalities were associated with delay in initial
      surgical procedure and in transfer to the burn center. The similarity of
      necrotizing fasciitis and invasive burn wound infection makes the burn center the
      ideal setting for the treatment of this disease. We advocate the addition of
      necrotizing fasciitis to the list of conditions currently recognized by the
      American Burn Association as appropriate for burn center transfer and care.

PMID- 12792232
TI  - Cholesterol and interleukin-6 concentrations relate to outcomes in burn-injured
      patients.
AB  - The goal of this study was to determine the relationship among lipid
      concentrations, cytokine concentrations, and clinical outcomes of burn patients.
      Twenty-eight patients admitted within 24 hours of burn injury, segregated based
      on burn size, had blood samples drawn 24 and 48 hours after burn injury and then
      weekly for 3 weeks. Measurements included total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride,
      interleukin (IL)-6, soluble IL-2 receptor, and soluble necrosis factor p55 and
      p75 receptors. Infection, length of stay (LOS), and survival were monitored.
      Cholesterol and lipoprotein concentrations decreased by at least 40% in patients
      with burns >20% total body surface area and inversely correlated with IL-6. Lower
      cholesterol and higher IL-6 values correlated with higher infection rates and
      longer LOS. IL-6 was the strongest predictor for LOS. In conclusion, outcomes
      after burn injury are related to low cholesterol and elevated IL-6 levels.

PMID- 12792233
TI  - Transcardiopulmonary thermal dye versus single thermodilution methods for
      assessment of intrathoracic blood volume and extravascular lung water in major
      burn resuscitation.
AB  - The purpose of this study was to compare the approximated values for
      intrathoracic blood volume (ITBV) and extravascular lung water (EVLW) obtained
      from a single indicator dilution to the exact data measured by double-indicator
      dilution. Eighteen patients with an average TBSA of 46.3% (range, 26 to 67%) and
      an average abbreviated burn severity index of 8.7 (range, 7 to 11) were included
      into a intraindividual comparative prospective study over a 20-month period. The
      COLD Z-021 system (Pulsion Medical Systems, Munich, Germany) was used to obtain
      both the exact measurements, as well as the estimated values for ITBV and EVLW.
      Two hundred ninety intraindividually comparative measurements were performed
      during the first 4 days after the burn injury. A good correlation between both
      techniques was shown for ITBVI (0.77; P <.01) for the overall measurements.
      However, the overall bias demonstrated a standard deviation higher than the mean
      value (-87.4 +/- 136 ml/m2), and precision for the estimated values for ITBVI was
      poor (-491 to 783 ml/m2). Additional analyses demonstrated a poor but significant
      correlation for low states of ITBV (r =.37; P <.01), but no significant
      correlations were found between the techniques for normal and high ITBV states.
      Thus, the approximated ITBV obtained from single thermodilution should not be
      used to guide volume therapy in major burn resuscitation. Furthermore, the EVLW
      is neither suitable for diagnostic use nor for therapeutic decisions because it
      is calculated on the basis of the poorly estimated values for ITBV in single
      thermodilution. Transcardiopulmonary single thermodilution is not suitable to
      assess intrathoracic blood volume and extravascular lung water in burn shock.
      However, the method is suitable to assess cardiac output and its derived
      parameters in burn resuscitation as shown in previous studies. It still must be
      proven whether the exactly measured ITBV obtained from transcardiopulmonary
      double-indicator dilution is superior to the commonly used parameters to guide
      major burn resuscitation.

PMID- 12792234
TI  - Change of complement system predicts the outcome of patients with severe thermal
      injury.
AB  - To establish the clinical relevance of the changes in the complement system in
      patients with thermal injury, we studied 20 patients who had third-degree burns
      on more than 60% of total body surface area. Their levels of the C3, C4, soluble
      C5b-9, and functional hemolytic activities of total (CH50) and alternative (AH50)
      complement pathways were sequentially measured for 2 weeks after thermal injury.
      All patients showed low C3 levels initially but increased C3 levels in the
      following days. The increasing trend of C3 levels was prominent in survivors but
      transient and diminished in nonsurvivors. The change of levels of C3, CH50, and
      AH50 was closely associated with one another, and their chronological trends
      related to the survival of patients (P =.0060,.0064 and.0066, respectively). The
      recovery of C3, AH50, and CH50 to normal or supranormal level during the early
      treatment period relates to the survival of patients with thermal injury. The
      failure of recovery of the complement system indicates a poor prognosis for
      patients and the monitoring of complement system might be beneficial in the care
      of patients with thermal injury.

PMID- 12792235
TI  - Silver-sulfadiazine eschar pigmentation mimics invasive wound infection: a case
      report.
AB  - A 3-year-old girl with 52% TBSA scalds, mostly partial thickness, was treated
      topically with 5% mafenide acetate solution and 1% silver sulfadiazine cream. All
      blood cultures and wound swabs were negative for the first 5 days. On day 6 gram
      negative bacteria and yeast forms were isolated from her wounds. High fever and
      leukocytosis were present and the child was treated with intravenous ampicillin
      and gentamicin according to sensitivity bacteriogram. The bacteria were
      identified as Pseudomonas aeruginosa and the yeast was Candida tropicalis. On day
      7, Escherichia coli was identified in blood cultures and intravenous cefixime was
      added. Amphotericin B was added on day 9 when blood cultures grew Candida
      tropicalis and Burkholderia cepacia. On day 13 dark pigmentation foci developed
      on some areas of partial-thickness burns in the back, resembling invasive wound
      infection. White blood cell count was 14,300 cells/mm3, and her body temperature
      reached 39.7 degrees C. Cultures from the pigmented areas were negative, and
      biopsies revealed deposits of silver. Most of the areas healed uneventfully, and
      only about 8% TBSA needed grafting, including some of the pigmented areas. No
      residual pigmentation remained on discharge.

PMID- 12792237
TI  - The media glorifying burns: a hindrance to burn prevention.
AB  - The media have a profound influence on the actions of children and adults. Burns
      and burn prevention tend to be ignored or even mocked. The purpose of this
      presentation is to reveal the callousness of the media in its dealings with burns
      and burn prevention. Printed materials with a relationship to burns, risk of
      burning, or disrespect for the consequences of burns were collected. The
      materials were tabulated into four categories: comics, advertisements (ads),
      articles that made light of burns, and television shows that portrayed behavior
      that would risk burn injury. Most burn-related materials were found in comics or
      advertisements. Several comics made light of high-risk behavior with flames,
      scald injury, contact injury, or burns. In addition, several advertisements
      showed people on fire or actions that could easily lead to burns. Several
      articles and televisions shows portrayed high-risk behavior that, in some
      instances, led to copycat injuries. Flames are frequently used to sell items that
      target adolescent boys or young men. The high incidence injuries that frequent
      this population parallel the high-risk behaviors portrayed by the media. The
      media portrays flames and high-risk behavior for burn injury as being cool,
      funny, and without consequence. The use of flames on clothing and recreational
      equipment (skateboards, hot rods) particularly targets the high-risk adolescent
      male. The burn community should make the media aware of the harm it causes with
      its callous depiction and glorification of burns.

PMID- 12792238
TI  - Playing with fire: images of fire on toy packaging.
AB  - Despite prevention efforts designed to teach children that fire is not a toy,
      each year hundreds of children, primarily male, are injured while playing with
      fire. Mass-produced toys and games shape children's behaviors, and the fire
      images on toy packaging may send the message that fire is fun rather than
      dangerous. The purpose of this study was to determine the frequency of male fire
      related injuries at our burn center and to investigate the use of fire images in
      toy packaging. An aisle-by-aisle search was conducted at a national toy store.
      Toys with fire images on their packaging were identified. Target gender and the
      setting in which the fire was displayed also were recorded. Only toys with
      clearly visible flames on their packaging were included. We reviewed our TRACS
      database from April 1997 to May 1999 for fire-related injuries to children
      admitted to our institution as a result of playing with fire. Review of toy
      stores revealed 404 toys with packaging containing fire images. Of these, 97%
      (393 of 404) were targeted to males. Video games were the leading category of
      flame-related packaging (208 of 404), followed by toy car/truck displays (84 of
      404). Packaging for girls' toys had safe and contained settings, whereas boys'
      toys used settings that were uncontrolled and associated with speed and weapons.
      A total of 59 children, 52 males and 7 females, with a mean age of 10 +/- 0.6
      years and mean TBSA burn of 12.3 +/- 2.1% were admitted to our facility with fire
      related injuries during the study interval. Children imitate life with toys and
      use play to experiment with new behavior. Boys are receiving a powerful,
      consistent message from images of fire on toy packaging. These advertisements may
      help to contribute to the higher incidence of fire-related injuries in boys.

PMID- 12792240
TI  - Comparative study of two systems of delivering supplemental protein with
      standardized tube feedings.
AB  - Burn patients often require protein supplementation for their nutritional
      support. Although these are often added to a commercial formula, published
      standards recommend a 4-hr hang time for manipulated open-system formulas in
      comparison with 24 hr for unopened closed systems. We hypothesized that use of
      standard closed-system formulas with the addition of protein flushes via the
      feeding tube twice daily would reduce nursing time and increase satisfaction. A
      pilot study included a time study comparing the two methods and a nursing
      satisfaction questionnaire. Management of an open system consistent with national
      standards took almost twice as much nursing time daily as the closed system with
      supplemental protein flushes (36.6 +/- 17.1 min vs 18.6 +/- 3.6 min; P =.051).
      Sixteen of 17 nurses preferred the closed system with protein flush. The results
      of this study were used to support expansion of the protocol change throughout
      the hospital.

PMID- 12792241
TI  - Regionalization of burn care--a concept whose time has come.

PMID- 12792242
TI  - Ball lightning encephalopathy.

PMID- 12792243
TI  - Abdominal computed tomography prolongs length of stay and is frequently
      unnecessary in the evaluation of acute pancreatitis.
AB  - BACKGROUND: Computed tomography (CT) can play a vital role in the diagnosis and
      staging of patients with acute pancreatitis. However, according to current
      guidelines, a CT examination should not be performed in all patients. We assessed
      the use of CT scanning in the evaluation of patients with acute pancreatitis at
      an urban teaching hospital. METHODS: Retrospective review of patients admitted
      with the diagnosis of acute pancreatitis from October 1999 to October 2001. We
      recorded demographics, laboratory values, severity of illness, length of stay,
      indication for CT, ordering physician, and outcome. RESULTS: Overall, 108
      patients met our inclusion criteria. Of these, 58 (54%) underwent CT examination.
      There was no difference (all P > 0.60) in markers of severity of illness in
      patients undergoing CT versus no CT. The only significant difference was length
      of stay (P = 0.003). Patients not undergoing CT were discharged a mean of 3 days
      sooner. Most appropriate CTs were ordered by the gastroenterology consultants as
      opposed to the emergency room and medical groups; however, this group's length of
      stay was longest (P = 0.035). CONCLUSIONS: In 1 teaching institution, physicians
      ordering CT for the evaluation of acute pancreatitis frequently do so without
      regard to the severity of patient illness. These examinations may prolong the
      length of hospitalization. Continued refinement and dissemination of guidelines
      for the diagnostic evaluation of acute pancreatitis is needed.

PMID- 12792244
TI  - Midodrine improves chronic hypotension in hemodialysis patients.
AB  - BACKGROUND: The effects of midodrine on chronic hypotension in hemodialysis (HD)
      patients have not been well investigated. METHODS: We evaluated midodrine's
      effect on autonomic function and hemodynamics in 12 HD patients who had chronic
      systolic blood pressure less than 100 mm Hg. Midodrine (5.0 mg) twice a day was
      given for 4 weeks. Another 12 age- and sex-matched HD patients with normotension
      were selected as a control group. Autonomic function tests included the heart
      rate responses to the Valsalva maneuver and 30:15 ratio as well as supine and
      standing blood pressure (BP) and sustained hand-grip test. Hemodynamic changes
      included 24-hour blood pressure, cardiac output, total peripheral resistance
      (TPR), and plasma renin and aldosterone concentrations. RESULTS: Compared with
      the control subjects, HD patients with chronic hypotension had more severe
      autonomic dysfunction and significantly lower TPR. After 4 weeks of midodrine
      therapy, sympathetic function (orthostatic and hand-grip tests) improved in
      conjunction with significant increases in mean arterial pressure (MAP) (79.5 +/-
      4.9 to 85.0 +/- 5.1 mm Hg, P < 0.05) and TPR (768 +/- 37 versus 1097 +/- 72
      dyne/sec/cm-5, P < 0.01) despite no significant change in Valsalva ratio, 30:15
      ratio, and cardiac output. MAP changes were positively correlated with TPR
      changes (r = 0.82, P < 0.001). Supine plasma renin activity was significantly
      increased. In addition, MAP during HD was also significantly increased during
      midodrine therapy. CONCLUSIONS: Midodrine improves chronic hypotension in HD
      patients by modulating autonomic function and its direct effects on peripheral
      vessels.

PMID- 12792245
TI  - Clinical implications of mycotoxins and Stachybotrys.
AB  - There has been considerable interest and concern in recent years regarding the
      potential health effects of mycotoxins in the indoor environment. Although the
      existence of mycotoxins has been known for several decades, relatively little is
      known about their effects in humans. What is known comes almost exclusively from
      studies of ingestion as the route of exposure. This review summarizes what is
      known regarding health effects of mycotoxins in general and specifically examines
      the evidence for the role of indoor exposure to the fungi of the genus
      Stachybotrys as a cause of disease in humans. Much work remains to be done in the
      area of mycotoxin research. The risk of health effects from ingestion seems much
      more widespread than from indoor airborne exposure, although the latter has
      received considerably more media attention. Rigorously controlled studies are
      needed to clarify these issues.

PMID- 12792246
TI  - Takayasu arteritis presenting as a pulmonary-renal syndrome.
AB  - Takayasu arteritis is an uncommon disease with a variety of presentations. We
      report a case of Takayasu arteritis with a presentation of a pulmonary-renal
      syndrome in a 22-year-old woman. She presented in acute respiratory failure with
      hemoptysis and acute renal failure; interestingly, however, the renal biopsy was
      normal. Magnetic resonance angiography (MRA) showed significant narrowing in the
      distal abdominal aorta with bilateral renal and common iliac artery occlusions.
      Thoracic and abdominal angiogram confirmed MRA findings of type IV Takayasu
      arteritis. Percutaneous transluminal angioplasty of the left renal artery
      normalized kidney function. The initial presentation of Takayasu arteritis as a
      pulmonary-renal syndrome with severe acute renal failure and diffuse pulmonary
      hemorrhage is unusual; to our knowledge, this has not been described previously
      in the literature. We provide a clinical review of Takayasu arteritis and a
      discussion of systemic manifestations pertinent to the case.

PMID- 12792247
TI  - Right-sided endocarditis complicating an atrial septal defect.
AB  - We report the case of a 45-year-old male patient not addicted to narcotic who
      presented with an infective endocarditis on the pulmonary valve. He was found to
      have an uncomplicated secundum-type atrial septal defect. This association is an
      extremely rare event.

PMID- 12792248
TI  - Adenoviral bronchopneumonia in an immunocompetent adult: computed tomography and
      pathologic correlations.
AB  - Acute febrile lung disease associated with "patchy ground-glass pattern" on high
      resolution computed tomography (HRCT) of the lung in an immunocompromised patient
      is suggestive of Pneumocystis carinii pneumonia; however, in an immunocompetent
      young person, it is suggestive of an atypical pneumonia, including viral
      bronchopneumonia. We studied a 31-year-old man who presented with fever, cough
      and hypoxemia. HRCT showed bilateral patchy ground-glass opacification. HIV test
      was negative and lung biopsy specimen grew adenovirus on viral culture.
      Histopathology of the lung was compatible with bronchopneumonia. In patients
      without HIV who present with acute lower respiratory infections and patchy ground
      glass opacification on HRCT, adenoviral bronchopneumonia should be included in
      the differential diagnosis.

PMID- 12792249
TI  - Syndrome of inappropriate secretion of antidiuretic hormone and nonpalpable
      purpura in a woman with Strongyloides stercoralis hyperinfection.
AB  - Strongyloidiasis stercoralis hyperinfection presenting as vasculitic-like skin
      lesions is rare. An autoinfection cycle allows intestinal strongyloidiasis,
      usually a benign infection, to persist for many decades. We report a woman with
      disseminated S stercoralis infection presenting as nonpalpable purpuric skin rash
      and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Upon
      admission, she was treated with corticosteroids for her vasculitic skin lesions,
      which then worsened her status. When the diagnosis was recognized, steroids were
      stopped, thiabendazole treatment was instituted, and she gradually recovered.
      Serious or fatal infection can occur in patients with strongyloidiasis who were
      treated with immunosuppressive drugs. Stool specimen screening and/or serological
      tests for S stercoralis infection in patients who require immunosuppressive
      therapy helps to prevent complications before embarking on such treatment.
      Unexplained hyponatremia, severe hypoalbuminemia without proteinuria, and unusual
      skin rashes, especially over the lower aspect of the abdomen and upper aspects of
      the thighs, in persons living in areas endemic to S stercoralis should raise
      suspicion of S stercoralis infection.

PMID- 12792250
TI  - Terbinafine-associated hepatotoxicity.
AB  - Terbinafine, an orally and topically active agent licensed for treatment of
      dermatophytic infection, has gained rapid worldwide acceptance in medical
      practice. Despite its fairly benign profile of adverse reactions, liver toxicity
      has occasionally been linked to terbinafine. This report describes a patient with
      severe cholestatic hepatitis associated with use of terbinafine. The patient was
      treated successfully with corticosteroids after partial response to
      ursodeoxycholic acid and cholestyramine. We attempt to identify risk factors for
      terbinafine-induced hepatotoxicity by an analytical review of all relevant
      literature. The mechanism underlying terbinafine hepatotoxicity could be more
      than just an idiosyncratic reaction. 7,7-dimethylhept-2-ene-4-ynal (TBF-A), the
      allylic aldehyde metabolite of terbinafine, may play a role in the pathogenesis
      of its hepatotoxicity. Our analysis supports monitoring patients clinically and
      measuring liver biochemistry through periodic blood tests, after confirming
      normal liver function at the onset of therapy with terbinafine. Early detection
      of abnormal hepatic function should prompt immediate discontinuation of this drug
      along with further evaluation.

PMID- 12792251
TI  - Granulocyte and monocyte adsorption apheresis in a patient with antiglomerular
      basement membrane glomerulonephritis and active ulcerative colitis.
AB  - A 58-year-old woman with Goodpasture syndrome and active ulcerative colitis is
      described. On admission, the patient had exertional dyspnea, hemoptysis, severe
      hypertension, and peripheral edema. Her serum levels of urea nitrogen and
      creatinine were increased, and her hemoglobin concentration was reduced. The
      patient had a rapidly progressive glomerulonephritis with acute renal failure.
      She was treated with methylprednisolone, cyclophosphamide, and plasmapheresis but
      failed to regain renal function. Circulating anti-glomerular basement membrane
      (anti-GBM) antibody was positive; however, serum antinuclear antibody, proteinase
      3-antineutrophil cytoplasm antibody and myeloperoxidase-antineutrophil cytoplasm
      antibody were negative. Nineteen months after initial presentation, she developed
      abdominal pain and severe diarrhea. These symptoms did not improve with
      conventional treatment. Colonoscopy performed after 3 months showed multiple
      ulcers in the colon. She was diagnosed with ulcerative colitis. She underwent
      granulocyte and monocyte adsorption apheresis once per week for 5 weeks. At 8
      weeks, her symptoms had improved; her stool number was markedly decreased, and
      the bloody stools and abdominal pain disappeared. These results suggest that
      granulocyte and monocyte apheresis may be of benefit in the therapy of a patient
      with ulcerative colitis who previously had Goodpasture syndrome

PMID- 12792252
TI  - Massive hemoptysis caused by endobronchial schwannoma in a patient with
      neurofibromatosis 2.
AB  - Neurogenic tumor of the lung is very uncommon. To the best of our knowledge,
      endobronchial schwannoma complicated by massive hemoptysis in a patient with
      neurofibromatosis 2 has not been reported previously. We report a case of
      endobronchial schwannoma complicated by massive hemoptysis in an 18-year-old man
      with neurofibromatosis 2. The diagnosis of neurofibromatosis 2 was established by
      demonstration of bilateral vestibular schwannomas on magnetic resonance imaging
      of the brain and pathologic examination of the resected brain tumors. Massive
      hemoptysis developed after surgical removal of the brain tumors in this patient.
      Bronchoscopy was done immediately after the first episode of hemoptysis and a
      tumor protruding from the orifice of the right lower lobe bronchus was found.
      Despite 2 additional bronchoscopies to stop bleeding and ameliorate airway
      obstruction in the consecutive 2 days, hemoptysis recurred rapidly and caused
      profound oxygen desaturation. The patient was subjected to right lower lobectomy
      and endobronchial schwannoma was evidenced pathologically.

PMID- 12792253
TI  - Research mentors: an understated value?

PMID- 12792254
TI  - Self-reported sleep quality and fatigue correlates with actigraphy in midlife
      women with fibromyalgia.
AB  - BACKGROUND: Limited data are available on the relationship between self-reported
      sleep quality, fatigue, and behavioral sleep patterns in women with fibromyalgia
      (FM). OBJECTIVES: To compare self-reported sleep quality, fatigue, and behavioral
      sleep indicators obtained by actigraphy between women with FM and sedentary women
      without pain, and to examine relationships among these variables. METHODS: Twenty
      three women with FM (M = 47.3, +/- 6.7 years) and 22 control women (M = 43.5, +/-
      8.2 years) wore an actigraph on the nondominant wrist for 3 consecutive days at
      home. Each day women reported bedtimes, rise times, and ratings of sleep quality
      and fatigue in a diary. Self-reported sleep quality, fatigue, and indicators of
      sleep quality obtained from actigraphy (e.g., total sleep time, sleep efficiency,
      sleep latency, wake after sleep onset, and fragmentation index) were averaged.
      The Mann Whitney U test was used to assess group differences. Pearson Product
      Moment Correlation was used to evaluate relationships between sleep quality and
      fatigue, and among sleep quality, fatigue, and actigraphy sleep indicators.
      RESULTS: Women with FM reported poorer sleep quality and more fatigue compared to
      controls (both p <.001). Actigraphy sleep indicators were not different between
      groups. In women with FM but not in controls, self-reported sleep quality was
      directly related to actigraphy indicators of total sleep time (r =.635, p <.01)
      and inversely related to sleep fragmentation (r = -.46, p <.05). Fatigue in women
      with FM was directly related to actigraphy indicators of wake after sleep onset
      (r =.57, p <.01), and inversely related to sleep efficiency (r = -.545, p <.01).
      DISCUSSION: Self-reported sleep quality and fatigue are associated with
      behavioral indicators of sleep quality at home in women with FM. Actigraphy is a
      useful objective measure of improved sleep outcomes in intervention studies.

PMID- 12792255
TI  - Theory of planned behavior-based models for breastfeeding duration among Hong
      Kong mothers.
AB  - BACKGROUND: The theory of planned behavior (TPB) has been used to explain
      breastfeeding behaviors in Western cultures. Theoretically-based investigations
      in other groups are sparse. OBJECTIVE: To evaluate cross-cultural application of
      TPB-based models for breastfeeding duration among new mothers in Hong Kong.
      METHOD: First-time breastfeeding mothers (N = 209) with healthy newborns provided
      self-reports of TPB predictor variables during postpartum hospitalization and
      information about breastfeeding experiences at 1, 3, 6, 9, and 12 months
      postdelivery or until they weaned. Three predictive models were proposed: (a) a
      strict interpretation of the TPB with two added proximal predictors of
      breastfeeding duration; (b) a replication with modification of the TPB-based
      model for more fully employed breastfeeding mothers from a previous study
      (Duckett et al., 1998); and (c) a model that posited perceived control (PC) as a
      mediating factor linking TPB motivational variables for breastfeeding with
      breastfeeding intentions and behavior. LISREL was used for the structural
      equation modeling analyses. RESULTS: Explained variance in PC and duration was
      high in all models. Overall fit of the strict TPB model was poor (GOFI = 0.85).
      The TPB for breastfeeding employed women and the PC-mediated models fit equally
      well (GOFI = 0.94; 0.95) and residuals were small (RMSR = 0.07). All hypothesized
      paths in the PC-mediated model were significant (p <.05); explained variance was
      0.40 for perceived control and 0.36 for breastfeeding duration. DISCUSSION:
      Models were interpreted in light of the TPB, previous findings, the social
      context for breastfeeding in Hong Kong, and statistical model-building. Cross
      cultural measurement issues and the need for prospective designs are continuing
      challenges in breastfeeding research.

PMID- 12792257
TI  - Ethical conflict associated with managed care: views of nurse practitioners.
AB  - BACKGROUND: Ethical conflict of nurse practitioners (NPs) practicing within a
      managed care environment has not been systematically examined, yet like physician
      practitioners, NPs are confronted with daily ethical conflicts. OBJECTIVE: To
      determine perceptions toward ethical conflict in practice espoused by NPs
      affiliated with managed care systems and to identify the relationship between
      selected individual, organizational, and societal/market contextual factors and
      ethical conflict in practice. METHOD: Descriptive, cross-sectional, correlational
      survey of a stratified random sample of 700 NPs licensed and certified to
      practice in the state of Maryland, conducted from November 2000 to January 2001.
      RESULTS: A majority of respondents reported being moderately to extremely
      concerned with managed care. Eighty percent of the sample perceived that it was
      sometimes necessary to bend managed care guidelines with 61% agreeing that the
      practitioner must weigh the patient's interest against managed care
      organizations' interests. The NPs in a staff/group model health maintenance
      organization (a) were less ethically concerned (p <.001); (b) perceived the
      ethical environment more positively (p <.001); and (c) had lower ethical conflict
      scores (p <.001) than NPs in other types of practice settings. DISCUSSION:
      Results from this study indicate that NPs are experiencing ethical conflict
      associated with practicing within a managed care environment; however, NPs in a
      staff/group model health maintenance organization report these concerns less.
      Ethical support through intervening strategies (i.e., ethics education and
      interdisciplinary ethics support systems) may help mitigate the conflict
      associated with this system of care.

PMID- 12792256
TI  - Treatment seeking for acute myocardial infarction symptoms: differences in delay
      across sex and race.
AB  - BACKGROUND: Patients experiencing an acute myocardial infarction are known to
      delay seeking treatment between 2 and 4 hours. This delay is problematic because
      individuals who receive treatment 2 or more hours after the onset of symptoms are
      less likely to benefit from emergent reperfusion techniques. Persons most likely
      to delay seeking treatment for an acute myocardial infarction and their reasons
      have not been clearly identified. OBJECTIVE: The purpose of this study was to
      identify the effect of selected demographic, clinical, cognitive, and
      environmental variables on the length of the time of delay. In addition, the
      study was designed to identify whether women delayed longer than men, and whether
      African Americans delayed longer than non-Hispanic Whites during an acute
      myocardial infarction. METHOD: A structured interview was conducted in a
      convenience sample (N eq> 212) of African American and non-Hispanic White
      patients hospitalized after acute myocardial infarction. Patients were asked
      detailed information about the sequence of events prior to the acute myocardial
      infarction, and the symptoms experienced. Medical records were examined for
      clinical information. RESULTS: Women did not delay significantly longer than men
      (2.0 vs. 2.5 median hours). African Americans delayed significantly longer than
      non-Hispanic Whites (3.25 hours vs. 2.0 median hours). Race did not contribute
      unique variance to delay time in a simultaneous multiple regression analysis;
      however, race was a significant predictor variable in whether or not participants
      sought treatment within the first hour after the onset of symptoms. The variance
      in delay time for African American and Non-Hispanic White men and women that
      could be explained by the predictor variables ranged from 23-47%. CONCLUSIONS:
      The reasons for delay differed in part by sex and race.

PMID- 12792258
TI  - A re-examination of the validity and reliability of the School-Age Temperament
      Inventory.
AB  - BACKGROUND: As a construct, temperament provides a framework for understanding
      differences among individuals in reaction to their life experiences. The
      measurement of the construct concerns both researchers and clinicians. OBJECTIVE:
      The purpose of this study was to examine whether the School-Age Temperament
      Inventory continued to demonstrate reliability and validity when retested with
      three existent samples of parent respondents. METHOD: Sample 1 was a
      sociodemographically and racially heterogeneous group of 200 children from New
      England in the United States. Data for Sample 2 was provided by 589 mothers and
      fathers from the state of Georgia in the United States. In Sample 3, data was
      provided by parents (principally, mothers) of 1,391 adolescents from Australia.
      Orthogonal Procrustes rotations were conducted to examine the underlying
      structure of the inventory when it was contrasted with the results obtained in
      the original standardization of the tool. RESULTS: The total coefficients of
      congruence for the samples were .88 to .97, while those of the four factors
      ranged from .84 to .98. Across the samples, Cronbach alphas for the dimensions
      ranged from .80 to .92. Independent t-tests identified that boys were
      significantly more active and less task persistent than girls. However,
      regression analyses revealed that sex accounted for only 5% of the variance in
      task persistence and activity. DISCUSSION: The results provide substantial
      additional support for the reliability and validity of the School-Age Temperament
      Inventory. Recommendations for future research are offered which include
      exploring the role of temperament in contributing to developmental outcomes in
      children and examining cross-cultural samples.

PMID- 12792259
TI  - Cognitive-behavioral intervention effects on adolescents' anxiety and pain
      following spinal fusion surgery.
AB  - BACKGROUND: Cognitive-behavioral interventions, typically effective in reducing
      anxiety and pain, have not been applied to adolescents undergoing major
      orthopaedic surgery. OBJECTIVES: To determine the effectiveness of three
      cognitive-behavioral interventions for reducing adolescents' postoperative
      anxiety and pain following spinal fusion surgery for scoliosis, and whether
      effectiveness depended on preoperative anxiety and age. METHODS: A randomized
      controlled trial with four groups receiving a videotape intervention (information
      only, coping only, information plus coping, or control) used a convenience sample
      of 109 adolescents (88 female, 93 White), 11-18 years of age (M = 14).
      Speilberger's (1983) State Anxiety scale assessed anxiety preoperatively and
      postoperatively on Day 2. A visual analogue scale assessed pain postoperatively
      on Days 2 and 4. RESULTS: Information plus coping was most effective for reducing
      postoperative anxiety in adolescents with high preoperative anxiety. Coping
      instruction led to less postoperative anxiety and pain for adolescents ages 13
      and younger. The control group reported the highest levels of pain on Day 4.
      CONCLUSIONS: Cognitive-behavioral interventions designed to prepare adolescents
      for surgery should be tailored to individual factors and developmental needs,
      especially the adolescents' preoperative anxiety level and age.

PMID- 12792260
TI  - The influence of relationships on children's and adolescents' participation in
      research.
AB  - BACKGROUND: Since the 1950s, children and adolescents have been defined as a
      vulnerable group for research participation. In 1998, federal mandates were
      issued to include children in clinical research. OBJECTIVES: The purpose of this
      qualitative study was to describe children and adolescents' understanding of
      research and the sociocultural factors that influenced them to become involved
      and continue participation in clinical research. The specific objective of the
      study findings reported here was to describe how relationships with adults (e.g.,
      parents and investigators) influenced children and adolescent involvement in
      clinical research. METHOD: This study employed qualitative methods, using
      semistructured interviews and narrative analytic techniques. There were 34
      children and adolescent participants, (8-22 years of age) who had a diagnosis of
      either diabetes or a hematological malignancy. Participants were interviewed to
      obtain an understanding of their experience with the assent/consent process for a
      research study. All interviews were transcribed verbatim from the audiotapes.
      RESULTS: Three themes discussed in this article were related to the
      child/adolescent's relationships with powerful adults: (a) faith in their
      parent(s), (b) relationships with members of the research/medical team, and (c)
      the child's perception of what happens when a child/adolescent and his/her parent
      disagree about research participation. DISCUSSION: Chronically ill children are
      willing to dialog about their involvement in research trials, and describe how
      relationships with their parents and clinician/investigators influence them. They
      can articulate their ability and right to make the decisions about involvement in
      research, along with their parent(s).

PMID- 12792261
TI  - Revision of the Facts on Osteoporosis Quiz.
AB  - BACKGROUND: Few instruments exist that measure knowledge of osteoporosis, a
      health risk for 28 million Americans. The original Facts on Osteoporosis Quiz
      (FOOQ), which was theoretically informed by Orem's (1995) Self-Care Theory, was
      published in 1998. In 2000, the National Institutes of Health (NIH) held a
      consensus conference on osteoporosis in which previous knowledge was modified
      based on current science. OBJECTIVES: The goal was to update the original
      instrument based on the latest scientific evidence and to determine its
      psychometric properties. METHOD: The quiz content was validated by osteoporosis
      experts and is theoretically informed by Orem's (2001) Self-Care Theory. An
      iterative process was used to design an instrument with an acceptable reading
      level. Reliability, item discrimination, and item difficulty were assessed in a
      convenience sample of 256 participants. RESULTS: The revised quiz, content-based
      on the 2000 NIH osteoporosis consensus conference, includes 20 questions. The
      quiz has a content validity index of.87, an internal consistency reliability
      of.76 and a 6th grade reading level. Item difficulty and item discrimination are
      also reported. CONCLUSIONS: The revised version of the FOOQ provides a valid,
      reliable, and theoretically informed instrument with acceptable psychometric
      properties.

PMID- 12792262
TI  - Interpretation/analysis methods in hermeneutic interpretive phenomenology.
AB  - BACKGROUND: Although hermeneutical interpretive phenomenological methodology has
      been used in many nursing research studies, reports of findings are generally not
      specific regarding the analysis, or "interpretive process," of this methodology.
      APPROACH: The purpose of this article is to assist researchers in analyzing
      interviews and observations, as part of hermeneutical interpretive phenomenology.
      In this article the interpretive process is explained, illustrated by examples
      from a recent research study. RESULTS: Other facets of the methodology including
      research question development, sampling issues, and interview and observation
      methods are briefly reviewed. DISCUSSION: Approaching the interpretive process as
      systematically as possible within a nonlinear methodology streamlines and
      clarifies interpretations of the interview data.

PMID- 12792263
TI  - Pharmaceutical influence?

PMID- 12792264
TI  - Why "techno-slang" at the end of life?

PMID- 12792265
TI  - Estrogen and insulin crosstalk: breast cancer risk implications.

PMID- 12792267
TI  - Advance directives: a guide for patient discussions.

PMID- 12792266
TI  - "GOLD" standards for acute exacerbation in COPD.

PMID- 12792268
TI  - Reality check: 10 barriers to advance planning.

PMID- 12792269
TI  - The importance of mammography screening in elderly women.

PMID- 12792270
TI  - Inflammatory breast cancer in primary care.

PMID- 12792271
TI  - The Teacher's Notebook: an innovative way to preparing teacher-scholars.

PMID- 12792272
TI  - Identifying the ideal qualities of a new graduate.

PMID- 12792273
TI  - A pre-college program for culturally diverse high school students.

PMID- 12792274
TI  - End-of-life nursing education consortium curriculum: an introduction to
      palliative care.

PMID- 12792275
TI  - RN to BSN program: transition from traditional to online delivery.

PMID- 12792276
TI  - Enhancing student leadership development in community settings.

PMID- 12792277
TI  - Teaching the code book: preparation for data entry.

PMID- 12792278
TI  - Beyond content: generating critical thinking in the classroom.

PMID- 12792279
TI  - The HESI exit exam: progression benchmark and remediation guide.

PMID- 12792280
TI  - Nursing administrative research: the underpinning of decisive leadership.

PMID- 12792281
TI  - Nursing values and a changing nurse workforce: values, age, and job stages.
AB  - OBJECTIVES: To identify the extent values are associated with age group and job
      stage; job satisfaction, productivity, and organizational commitment; as well as
      education, generation, ethnicity, gender, and role. BACKGROUND: Values direct the
      priorities we live by and are related to employee loyalty and commitment. Lack of
      congruency between a nurse's personal values and those of the organization
      decrease satisfaction and effectiveness and may lead to burnout and turnover.
      Little research has been done on whether values differ by age, generations, or
      job stages. METHODS: Nurses in all roles (N = 412) in three hospitals in Los
      Angeles County were randomly surveyed, using valid and reliable instruments to
      measure the variables of interest. RESULTS: Nurses in the top third for job
      satisfaction, organizational commitment, and productivity showed higher scores
      for many values including their associates, creativity, esthetics, and
      management, while those in the bottom third scored higher in economic returns
      only. Nurses in different generations differed little; younger generations placed
      higher values on economic returns and variety. CONCLUSIONS AND IMPLICATION:
      Management strategies to meet nurses' values and increase their satisfaction and
      retention are presented.

PMID- 12792282
TI  - Predicting registered nurse job satisfaction and intent to leave.
AB  - BACKGROUND: Nurse job dissatisfaction has been the primary predictor of intent to
      leave; however, although many predictors of job satisfaction have been
      identified, little is known about the influence of variable nurse attitudes, such
      as psychological empowerment and hardiness, on job satisfaction. OBJECTIVE: The
      purpose of this study was to investigate the relative influence of nurse
      attitudes, context of care, and structure of care on job satisfaction and intent
      to leave. METHODS: A nonexperimental, predictive design evaluated these
      relationships in a nonrandom sample of 90 registered staff nurses using
      instruments with known psychometric properties. RESULTS: The major predictor of
      intent to leave was job dissatisfaction, and the major predictor of job
      satisfaction was psychological empowerment. Predictors of psychological
      empowerment were hardiness, transformational leadership style, nurse/physician
      collaboration, and group cohesion. CONCLUSIONS: Results supported the influence
      of nurse attitude on job satisfaction relative to other contributing factors.

PMID- 12792283
TI  - Charge nurse leadership development and evaluation.
AB  - OBJECTIVE: To describe the development and evaluation of a permanent charge nurse
      role and report outcomes of this leadership model over 4 years. BACKGROUND: A
      permanent charge nurse role was developed to improve continuity of care and
      develop emerging nurse leaders. An evaluation model was constructed to measure
      program outcomes. Kouzes and Posner's Leadership Model served as the theoretical
      framework. METHODS: The permanent charge nurse role was developed, training
      planned, and the evaluation framework established. Measurements included two
      survey instruments, an investigator-developed End-of-Shift Report, and
      institutional patient satisfaction data. Survey instruments included Kouzes and
      Posner's Leadership Practice Inventory (LPI), concurrently measuring self
      (charge) and other (staff) perceptions of charge leadership. The McClosky Mueller
      Satisfaction Scale (MMSS) measured charge and staff nurse job satisfaction. Data
      were collected at baseline, post-implementation, and additional time periods.
      RESULTS: Charge RNs reported significantly more favorable perceptions of
      leadership abilities than staff. The Shift Report successfully tracked both
      system and charge management issues. Patient satisfaction data did not yield data
      due to vendor changes. Job satisfaction results showed charge nurses reported
      higher satisfaction with schedule, praise and recognition, control and
      responsibility, than staff nurses. CONCLUSIONS: Using data to evaluate charge
      nurse leadership guides continued program improvements.

PMID- 12792284
TI  - Factors that influence nurses' job satisfaction.
AB  - OBJECTIVE: To examine factors affecting the job satisfaction of registered nurses
      (RNs). BACKGROUND: A growing recognition of job dissatisfaction among RNs in
      South Carolina hospitals has contributed to current problems with recruitment and
      retention. If administrators identify factors influencing RNs' job satisfaction
      in hospitals and implement strategies to address these factors, RN turnover rates
      will decrease and recruiting and retention rates will increase. METHODS: A cross
      sectional study of secondary data was designed to identify the individual, work,
      and geographic factors that impact nursing job satisfaction at the state level. A
      27-question self-administered survey was sent to 17,500 RNs in South Carolina
      with postage-paid envelopes for their responses. Surveys from 3472 nurses were
      completed anonymously. Univariate statistics were used to describe the study
      sample. One-way and multivariable Analysis of Variance were used to determine
      which variables contributed the most to job satisfaction. RESULTS: For about two
      thirds of the RNs, job satisfaction remained the same or had lessened over the
      past 2 years. In addition, statistically significant differences were found
      between job satisfaction and years of service, job position, hospital retirement
      plan, and geographic area. CONCLUSIONS: The findings have implications for nurse
      managers and hospital administrators for planning and implementing effective
      health policies that will meet the unique needs of their staffs and
      organizations. Such research is particularly relevant in this difficult time of
      nursing shortages throughout the healthcare industry.

PMID- 12792285
TI  - Nursing administration graduate programs: current status and future plans.
AB  - BACKGROUND: Much controversy has been reported in the literature regarding the
      value of graduate programs in nursing administration. Yet a rapidly changing
      healthcare delivery system requires that nurse administrators be well prepared to
      deal with a fiscally restrained environment that demands the delivery of high
      quality care OBJECTIVE: The purpose of our study was to investigate the current
      status and future plans of graduate programs in nursing administration. We
      particularly focused on anticipated program reforms and relationships with
      external stakeholders. METHOD: A survey was mailed to 338 National League for
      Nursing Accrediting Commission and Commission on Collegiate Nursing Education
      accredited master's programs. Data from 105 completed surveys were analyzed
      descriptively. RESULTS AND CONCLUSIONS: Graduate programs in nursing
      administration are alive and well. Programs appear to be adding needed content as
      suggested by the American Association of Colleges of Nursing and American
      Organization of Nursing Executives and others to keep pace with a changing
      healthcare delivery system. Programs continue to explore creative ways to reach
      more students with fewer faculty resources.

PMID- 12792286
TI  - Isoflavones: food for thoughtful consideration.

PMID- 12792287
TI  - What affects bladder function more: menopause or age?

PMID- 12792288
TI  - Ultrasound assessment of ovarian volume: does ovarian size matter?

PMID- 12792289
TI  - Isoflavones and cognitive function in older women: the SOy and Postmenopausal
      Health In Aging (SOPHIA) Study.
AB  - OBJECTIVE: This study examines the effects of a dietary supplement of isoflavones
      on cognitive function in postmenopausal women. DESIGN: Participants for this 6
      month, double-blind, randomized, placebo-controlled clinical trial were women who
      were in good health, were postmenopausal at least 2 years, and were not using
      estrogen replacement therapy. Between July 24, 2000, and October 31, 2000, 56
      women aged 55 to 74 years were randomized; 2 in the placebo group and 1 in the
      active treatment group did not complete the 6-month evaluation, and none withdrew
      because of adverse effects. Women randomized to active treatment (n = 27) took
      two pills per day, each containing 55 mg of soy-extracted isoflavones (110 mg
      total isoflavones per day; Healthy Woman: Soy Menopause Supplement, Personal
      Products Company, McNeil-PPC Inc., Skillman, NJ, USA). Women assigned to placebo
      (n = 26) took two identical-appearing pills per day containing inert ingredients.
      Cognitive function tests administered at baseline and follow-up included the
      following: Trails A and B, category fluency, and logical memory and recall (a
      paragraph recall test assessing immediate and delayed verbal memory). RESULTS: At
      baseline, all women were cognitively intact; there were no significant
      differences by treatment assignment in age, education, depressed mood, or
      cognitive function (all P values > 0.10). Compliance was 98% and 97%,
      respectively, in the placebo and treatment groups; all women took at least 85% of
      their pills. The women in the treatment group did consistently better, both as
      compared with their own baseline scores and as compared with the placebo group
      responses at 6 months. Comparisons of percentage change in cognitive function
      between baseline and follow-up showed greater improvement in category fluency for
      women on active treatment as compared with the case of those on placebo (P =
      0.02) and showed (nonsignificantly) greater improvement on the two other tests of
      verbal memory and Trails B. CONCLUSION: These results suggest that isoflavone
      supplementation has a favorable effect on cognitive function, particularly verbal
      memory, in postmenopausal women.

PMID- 12792291
TI  - Ovarian volume in pre- and perimenopausal women: a population-based study.
AB  - OBJECTIVE: To evaluate the relationship between ovarian volume and age, hormonal
      levels, obesity, and phase of menstrual cycle in pre- and perimenopausal women.
      DESIGN: A study was carried out with 98 women from the general population who
      were not receiving drugs known to interfere with hormonal levels. Right and left
      ovary volume was measured by ultrasound. Blood samples were drawn for estradiol,
      follicle-stimulating hormone, and luteinizing hormone determinations. RESULTS:
      Fourteen women were excluded because of the presence of ovarian cysts. Mean
      ovarian volume for pre- and perimenopausal women was 7.1 +/- 3.1 cm3. There was
      no statistical difference in ovarian volume related to the phases of the
      menstrual cycle. Ovarian volume was significantly smaller in all age groups over
      40 years compared with the 35-to-39 age group (P < 0.05). No association was
      observed between ovarian volume and body mass index. In turn, age (P = 0.013) and
      follicle-stimulating hormone levels (P = 0.002) showed a significant negative
      correlation, and luteinizing hormone showed a significant positive correlation
      with ovarian volume (P = 0.005). CONCLUSIONS: Ovarian volume was smaller in pre-
      and perimenopausal women aged 40 years and older in relation with younger women.
      The current standard measurements of ovarian volume by transvaginal ultrasound
      should be reevaluated for pre- and perimenopausal women between 40 and 55 years
      of age.

PMID- 12792290
TI  - Is the occurrence of storage and voiding dysfunction affected by menopausal
      transition or associated with the normal aging process?
AB  - OBJECTIVES: To evaluate whether the increasing occurrence of urinary and voiding
      dysfunction is independently influenced by the transition from pre- to
      postmenopause or by the interactive and additive effects of age-associated
      changes in bladder and urethral function. DESIGN: Of the 1,584 women randomly
      sampled from a community-based health population, 1,253 (79.1%) were successfully
      interviewed. The participants were asked to reply to the Bristol Female Urinary
      Tract Symptoms Questionnaire regarding various storage symptoms and voiding
      dysfunction. The chi2 test and Cochran-Armitage trend test were used for
      analysis. RESULTS: The prevalence of storage symptoms such as frequency, urgency,
      nocturia, and urge incontinence in premenopausal and menopausal groups was 18.0%
      versus 29.8%, 9.8% versus 20.7%, 21.2% versus 38.2%, and 6.8% versus 15.7%,
      respectively (all P < 0.05). In premenopausal and menopausal groups, the
      prevalence of hesitancy, poor stream, incomplete emptying, voiding with abdominal
      straining, discontinuous urine flow, and dribbling was also significantly
      different (17.2% v 22.9%, 17.8% v 25.7%, 12.7% v 21.9%, 4.9% v 11.6%, 16.2% v
      24.5%, and 9.4% v 17.6%, respectively; all P < 0.05). However, the occurrences of
      various storage symptoms, namely, frequency, urgency, nocturia, and urge
      incontinence, as well as voiding symptoms such as incomplete emptying,
      discontinuous urine flow, and dribbling, were also significantly associated with
      the normal aging process (P < 0.05). CONCLUSIONS: Our results imply that the
      increasing occurrences of storage and voiding dysfunctions are not only affected
      by pre- and postmenopausal transition but are also closely associated with aging
      changes.

PMID- 12792292
TI  - Gabapentin for the management of hot flushes: a case series.
AB  - OBJECTIVE: To audit the effectiveness of the anticonvulsant gabapentin on hot
      flushes in postmenopausal women. DESIGN: This was an open case series involving
      11 postmenopausal women who were willing to take gabapentin for the relief of
      their hot flushes and were willing to keep a diary recording the number and
      intensity of their hot flushes, both before and during treatment. Gabapentin was
      started at a dose of 300 mg, to be taken at night, and the women were instructed
      to increase the dose up to 1,200 mg, according to symptom behavior. RESULTS:
      Eleven women agreed to participate for on average 53.22 days (range, 2-79 days),
      but two discontinued participation-one before starting treatment and one after 2
      days-so there are complete data sets for nine women. Gabapentin was found to be
      extremely effective in reducing hot flush activity (P < 0.001; Fig. 1). A
      significant reduction in symptoms was observed with a dose of 300 mg/day (P <
      0.001). Scores on the Green Climacteric Scale were significantly improved from a
      mean of 25.72 (range, 12-42) to 19.25 (range, 13-31; P < 0.001). Palpitations (P
      = 0.001), panic attacks (P = 0.0001), mood (P = 0.023), muscle and joint pains (P
      = 0.021), and paresthesias and loss of sensation in the extremities (P = 0.001)
      were also shown to improve with treatment. CONCLUSIONS: In the present case
      series, gabapentin was well tolerated and could be a valuable alternative for the
      treatment of hot flushes in women with contraindications to hormonal replacement
      therapy. It would be particularly beneficial for women in whom aches and pains
      and paresthesias are also a significant feature of the climacteric syndrome.

PMID- 12792293
TI  - Effects of tibolone on cell adhesion molecules in postmenopausal women.
AB  - OBJECTIVE: The first step in atherosclerosis is characterized by the adherence of
      lymphocytes and monocytes to cell adhesion molecules expressed by endothelial
      cells. Therefore, we wanted to investigate the effect of tibolone on the
      circulating levels of various cell adhesion molecules. DESIGN: Thirty
      postmenopausal women were enrolled in a double-blind, randomized, placebo
      controlled outpatient trial. RESULTS: Tibolone led to a significant decrease in
      soluble intercellular adhesion molecule-1, soluble intercellular adhesion
      molecule-3, and soluble vascular cell adhesion molecule-1, but had no effect on
      monocyte chemotactic protein-1. CONCLUSIONS: The direct favorable effects of
      tibolone on endothelial cells may explain the clinical benefits of this substance
      in terms of anti-ischemic effects and osteoporosis prevention.

PMID- 12792294
TI  - Postmenopausal women lose less visceral adipose tissue during a weight reduction
      program.
AB  - OBJECTIVE: Visceral adipose tissue (VAT) is increased in the postmenopausal
      state, which may contribute to an increase in cardiovascular diseases. This study
      was undertaken to investigate whether there is a difference in the change of VAT
      during a weight reduction program between premenopausal and postmenopausal obese
      women. DESIGN: This study was a longitudinal clinical intervention of a weight
      reduction program, including lifestyle modification and adjuvant pharmacotherapy,
      for 12 weeks in 21 premenopausal and 19 postmenopausal obese women. Weight,
      height, body fat percentage, and waist and hip circumferences were measured.
      Visceral, subcutaneous, and total adipose tissue of the abdomen were determined
      by CT scan at the level of L4-L5 before and after weight reduction. RESULTS: The
      percent changes in VAT and the visceral-to-subcutaneous adipose tissue ratio, as
      well as waist circumference and waist-to-hip ratio, in the postmenopausal women
      were significantly less than those in the premenopausal women, whereas the
      percent changes in hip circumference, fat mass, total adipose tissue, and
      subcutaneous adipose tissue were similar in the two groups. The association
      between percent changes of VAT and the percent change of waist circumference is
      stronger in postmenopausal than in premenopausal women. CONCLUSIONS: The
      postmenopausal women lost less VAT compared with the premenopausal women during
      the weight reduction program. This may make it more difficult for postmenopausal
      women to overcome the increased risk of cardiovascular diseases compared with
      premenopausal women.

PMID- 12792295
TI  - Population demographics and socioeconomic impact of osteoporotic fractures in
      Canada.
AB  - Through a survey of the literature and an analysis of selected national and
      regional statistics, a review of the incidence of osteoporosis and its
      consequences was performed. Results illustrate that the consequences of
      osteoporosis are preventable and should sensitize clinicians to the importance of
      early detection and the identification of risk factors for disease prevention and
      to early treatment once disease has been established. A marked increase in the
      annual incidence of hip fractures in all Canadians is noted. Whereas the
      incidence was less than 20,000 in 1981, the incidence of hip fracture grew to
      27,342 in 1995, with 73% occurring in women. It is estimated that in Canada at
      least one in four women older than 50 years will have one or more osteoporosis
      related fractures in their lifetimes. The consequences of these fractures are
      considerable, both for patients and healthcare services. Only half of all victims
      regain total autonomy, and the total direct costs in Canada stemming from
      osteoporosis are estimated to be $1.3 billion per year.

PMID- 12792296
TI  - Influences of hormone replacement therapy on postmenopausal women's health
      perceptions.
AB  - OBJECTIVE: To assess the beliefs of climacteric women regarding their health,
      menopause, and hormone replacement therapy (HRT). DESIGN: Medical students asked
      to interview 526 healthy women, ranging from 40 to 64 years of age, between
      January and February of 2002. Of that number, 26 (4.9%) declined to participate
      in the interview. Thus, 500 women were interviewed about their beliefs and
      perceptions regarding their quality of life and health risks, as well as their
      opinions on menopause and HRT. RESULTS: The mean age of the sample was 53.3 +/-
      6.2 years; 83.4% were postmenopausal, and 18.8% were HRT users. Of the women
      interviewed, 38.6% believed that their health was good. Although 78.8% thought
      that cancer is the main cause of death, 64% of them considered themselves to be
      at high risk for cardiovascular disease and osteoporosis. Most (64%) believed
      that menopause deteriorates the quality of life and that it increases
      cardiovascular risk (52.4%) and osteoporosis (72.0%). The HRT users perceived
      that they had better health status (48.9% v 36.2%, P < 0.02) and smaller
      cardiovascular risk (54.3% v 66.3%, P < 0.04) than did the nonusers; however,
      they ignored the preventive effect of estrogens in osteoporosis. CONCLUSIONS:
      Women believe that menopause deteriorates their health. The HRT users perceived
      themselves to be healthier and to have a smaller risk for cardiovascular disease.

PMID- 12792297
TI  - Effect of low-dose transdermal E2/NETA on the reduction of postmenopausal bone
      loss in women.
AB  - OBJECTIVE: To assess the efficacy of a continuous-combined transdermal patch
      (estradiol/ norethisterone acetate [E(2)/NETA] 25/125; Estragest TTS, Novartis,
      Basel, Switzerland) in the reduction of bone loss in postmenopausal women.
      DESIGN: In a 96-week, double-blind, randomized, multicenter, parallel study, 124
      healthy women with an intact uterus more than 4 years after menopause received
      either transdermal continuous-combined E(2)/NETA (0.025/0.125 mg/day) or placebo
      patch for 24 treatment cycles; diet was normalized for calcium intake. Lumbar
      spine bone mineral density (BMD) ranged from 0.969 to 0.805 g/cm2 with a mean
      annual BMD decrement ranging from 3% to 8% within the last 24 months. BMD at
      lumbar spine L(2)-L(4) (postero-anterior) and femur were assessed by dual energy
      x-ray absorptiometry after 6, 12, and 24 cycles. Efficacy variables included
      measurement of biochemical markers of bone turnover (3, 6, 12, and 24 months).
      RESULTS: BMD at lumbar spine was significantly higher at all time points in the
      E(2)/NETA group than in the placebo group (P < 0.0001). Significant increases in
      BMD (P < 0.0008) from baseline were observed at all sites after 24 months in the
      E(2)/NETA group compared with placebo, which demonstrated a decrease from
      baseline. At endpoint, statistically significant decrements in the values of bone
      remodeling markers were observed (P < 0.05) with E(2)/NETA. CONCLUSIONS:
      E(2)/NETA 25/125 Estragest TTS was more effective than placebo in reducing the
      activation frequency of bone remodeling and in preventing bone loss at the spine
      and hip. Effects on the hip were similar to those observed for higher doses of
      estrogen.

PMID- 12792298
TI  - Association of estrogen and vitamin D receptor gene polymorphisms with tooth loss
      and oral bone loss in Japanese postmenopausal women.
AB  - OBJECTIVE: To investigate the relationship between estrogen receptor (ER) and
      vitamin D receptor (VDR) gene polymorphisms and tooth loss, oral bone loss, and
      postcranial bone mineral density (BMD) in Japanese postmenopausal women. DESIGN:
      Polymorphisms at the ER PvuII and XbaI and VDR BsmI gene sites, number of teeth
      remaining, oral bone mass, and BMD of the lumbar spine and the hip were evaluated
      in 149 Japanese postmenopausal women. RESULTS: The distribution of ER PvuII and
      XbaI and VDR BsmI restriction fragment length polymorphisms was as follows: pp,
      30.2%; Pp, 49.7%; PP, 20.1%; xx, 71.8%; Xx, 22.5%; XX, 2.7%; bb, 76.5%; Bb,
      22.2%; and BB, 1.3%. Analysis of covariance adjusted for confounding variables
      revealed that participants with pp allele had fewer teeth remaining than did
      those with P allele. There were no significant differences in oral bone mass and
      postcranial BMD among three alleles at the PvuII site. Participants with X and bb
      allele had less oral bone mass and lower postcranial BMD than did those with xx
      and B allele, respectively. We could not clarify the positive associations
      between XbaI and BsmI polymorphism and number of teeth. CONCLUSIONS: PvuII
      polymorphism was associated with tooth loss, but not with oral bone mass and
      postcranial BMD. XbaI and BsmI polymorphisms may be associated with bone mass or
      density; however, PvuII polymorphism might contribute to another unknown pathway
      related to tooth loss.

PMID- 12792299
TI  - Psychometric properties of a menopausal symptom list.
AB  - OBJECTIVE: To determine psychometric properties of a brief menopause symptom list
      and its sensitivity to menopausal status in a population-based cohort of late
      reproductive-age women. DESIGN: A 12-item menopause symptom list (MSL)
      administered in a cohort of African American and Caucasian women aged 38 to 52
      years (N = 350) was psychometrically evaluated. Menopausal status of the cohort
      was determined by menstrual cycle dates obtained in interviews and participants'
      daily symptom records. Results of factor analysis were applied to longitudinal
      assessments of the cohort over a 3-year period. Convergent validity with other
      standard measures of mood, stress, health, and quality of life was determined.
      RESULTS: Internal consistency was found for the MSL items. Item total
      correlations are reported. Factor analysis identified three dimensions
      (psychological, somatic, and vasomotor). Multivariate analysis of cohort data
      over a 3-year interval showed that the menopausal symptoms increased over time (P
      = 0.0004) and that the identified factors were differentially associated with
      menopausal status. Psychological symptoms increased in the premenopausal and
      early transition groups but decreased in the late menopausal-postmenopausal
      groups (P = 0.0046 for the interaction). Vasomotor symptoms increased in both the
      early transition and late menopausal-postmenopausal groups (P = 0.0309 and P =
      0.0543, respectively). Psychological symptoms (factor 1) had high correlations
      with other standard symptom measures (Center for Epidemiologic Studies-Depression
      Scale, r = 0.59; Zung Anxiety Scale, r = 0.65), whereas factors 2 and 3 did not,
      suggesting that the somatic and vasomotor symptoms were not associated with mood
      or health problems. CONCLUSIONS: The MSL provides a brief questionnaire with
      acceptable psychometric properties for assessing three dimensions of menopause
      related symptoms and demonstrated sensitivity to menopausal status in a
      population-based cohort.

PMID- 12792300
TI  - Hormone therapy.

PMID- 12792301
TI  - Localized mucosal leishmaniasis due to Leishmania (Leishmania) infantum: clinical
      and microbiologic findings in 31 patients.
AB  - The clinical and microbiologic characteristics of 31 patients with mucosal
      leishmaniasis due to Leishmania (Leishmania) infantum are described. Twenty-eight
      (90%) patients were male. Mean age at presentation was 48 +/- 14 years. Thirteen
      (42%) patients had no underlying disease, while 18 (58%) patients had several
      other medical conditions. Fifteen (48%) patients were immunocompromised, 7
      patients were infected with human immunodeficiency virus (HIV), and 3 were graft
      recipients. The primary location of lesions was the larynx in 11 (35%) patients,
      oral mucosa in 10 (32%) patients, and the nose in 5 (16%) patients. Mucosal
      lesions were painless in all patients but 2 and consisted of whitish, red, or
      violaceous nodular swelling or tumorlike masses. Ulceration was reported in 6
      patients. Pathologically, the lesions showed a chronic inflammatory infiltrate.
      Granuloma may be seen. The localization of the lesions determined the
      symptomatology of the disease. Symptoms included hoarseness, difficulty
      swallowing, and nasal obstruction. The disease presentation was usually
      protracted, with a mean time from the onset of symptoms to diagnosis of 13 months
      (range, 3 wk-4.5 yr), and the clinical diagnosis was usually mistaken for
      neoplasia of the upper aerodigestive tract. No laboratory abnormalities were
      found in these patients due to the localized disease, apart from those attributed
      to underlying diseases. Parasites were easily identified in smears or sections by
      Giemsa stain or hematoxylin-eosin stain. Leishmania was grown in culture in 12
      (60%) patients; culture was negative in 8 (40%) patients. Leishmania (Leishmania)
      infantum was identified in only 9 instances. The following zymodemes were
      reported: MON-1 (2 patients), MON-24 (2 patients), MON-27 (1 patient), and MON-34
      (1 patient). Serologic test results were known in 25 patients. Serology was
      usually positive at low titer; 6 (24%) patients had negative serologic test
      results. Twenty patients were treated with antimonial compounds for between 3 and
      36 days. Three patients were given drugs other than antimonial drugs. Five
      patients were treated only locally, by surgery (3 patients) or topical medical
      therapy. One patient received no therapy, and treatment was not reported in 2
      cases. Patients were cured in 25 (89%) cases, and sequelae were uncommon (14%).
      Relapse was detected in 2 individuals and 1 patient developed visceral
      leishmaniasis after treatment. Two HIV-coinfected patients died of causes
      unrelated to leishmaniasis. The results of the present report stress the clinical
      importance of searching for the presence of Leishmania in patients with suspected
      neoplasia of the upper respiratory tract if they have visited or resided in zones
      endemic for Leishmania (Leishmania) infantum. The treatment of choice for these
      patients is not established yet, but most patients respond to antimonial
      compounds given for 28 days or less.

PMID- 12792302
TI  - Community-acquired pneumonia in very elderly patients: causative organisms,
      clinical characteristics, and outcomes.
AB  - We performed an observational analysis of prospectively collected data on 1,474
      adult patients who were hospitalized for community-acquired pneumonia; 1,169
      patients were under 80 years of age and 305 (21%) patients were over 80 years
      ("very elderly"). Mean patient ages were 60 years in the former group and 85
      years in the latter group. Severely immunosuppressed patients and nursing-home
      residents were not included. Comorbidities significantly associated with older
      age were chronic obstructive pulmonary disease, chronic heart disease, and
      dementia. The most common causative organism was Streptococcus pneumoniae (23% in
      both groups). Aspiration pneumonia was more frequent in the very elderly (5% in
      younger patients versus 10% in the very elderly); Legionella pneumophila (8% in
      younger patients versus 1% in the very elderly) and atypical agents (7% in
      younger patients versus 1% in the very elderly) were rarely recorded in the very
      elderly. While very elderly patients complained less frequently of pleuritic
      chest pain, headache, and myalgias, they were more likely to have absence of
      fever and altered mental status on admission. No significant differences were
      observed between groups as regards incidence of classic bacterial pneumonia
      syndrome (60% versus 59%) in 343 patients with pneumococcal pneumonia. The
      development of inhospital complications (26% in younger versus 32% in very
      elderly patients) as well as early mortality (2% in younger versus 7% in very
      elderly patients) and overall mortality (6% in younger versus 15% very elderly
      patients) were significantly higher in very elderly patients. Acute respiratory
      failure and shock/multiorgan failure were the most frequent causes of death,
      especially of early mortality. Factors independently associated with 30-day
      mortality in the very elderly were altered mental status on admission (odds
      ratio, 3.69), shock (odds ratio, 10.69), respiratory failure (odds ratio, 3.50),
      renal insufficiency (odds ratio, 5.83), and Gram-negative pneumonia (odds ratio,
      20.27).

PMID- 12792303
TI  - Reset osmostat and salt and water retention in the course of severe hyponatremia.
AB  - To evaluate whether a reset osmostat and salt and water retention may be features
      of the course of some patients with hyponatremia, we present the long-term course
      of 6 selected patients. Three patients had spinal cord injury, 3 had marked
      psychiatric problems, and 3 had alcoholism. Five developed severe hyponatremia
      superimposed on chronic hyponatremia consequent to a reset osmostat. In 5
      patients marked salt and water retention of unclear etiology occurred during
      therapy on 11 occasions. In 4 of these 11 episodes hypernatremia developed.
      Knowledge of a patient's past history and the possibility of developing salt and
      water overload should influence therapy.

PMID- 12792304
TI  - Anti-epiligrin cicatricial pemphigoid: clinical findings, immunopathogenesis, and
      significant associations.
AB  - We report the clinical and immunopathologic findings in a cohort of 35 patients
      with anti-epiligrin cicatricial pemphigoid (AECP). These patients have a mucosal
      predominant subepithelial blistering disease that is clinically indistinguishable
      from other forms of cicatricial pemphigoid. The mucosal surfaces of the mouth and
      eye are most commonly involved. The skin is also involved in most patients, but
      usually this is less severe than mucosal involvement. AECP is characterized by
      the binding of circulating IgG autoantibodies to the dermal side of 1M NaCl split
      human skin on indirect immunofluorescence microscopy. These IgG antibasement
      membrane autoantibodies target laminin 5, a heterotrimeric protein consisting of
      alpha3, beta3, and gamma2 subunits. IgG autoantibodies predominantly target the G
      domain within the alpha subunit. The presence of circulating IgG autoantibodies
      are specific for the diagnosis of AECP and are not seen in patients with other
      autoimmune blistering diseases or normal volunteers. Furthermore, we expand on
      data previously reported on the finding of an increased relative risk for solid
      cancer in patients with AECP, especially in the first year after blister onset.
      The majority of cancers documented in a cohort of 35 patients assembled over 12
      years of study were adenocarcinomas that were at an advanced stage at their time
      of detection. This circumstance is thought to account for a high incidence of
      mortality among AECP patients who develop an associated cancer. AECP patients
      also demonstrate a significant risk for mortality as a consequence of treatment
      with systemic immunosuppressives. The current longitudinal study suggests that
      only a minority of AECP patients go into remission.

PMID- 12792305
TI  - Retinal lesions as clues to disseminated bacterial and candidal infections:
      frequency, natural history, and etiology.
AB  - Invasive bacterial and candidal infections are known to involve the retina, but
      the natural history of the retinal lesions and the utility of ophthalmologic
      consultation in the critical care setting as a diagnostic tool are not well
      understood. We 1) performed weekly funduscopic examinations on 77 medical and
      surgical patients in intensive care units (ICUs), 2) analyzed results of serial
      ocular examinations in 180 non-neutropenic patients with candidemia, and 3)
      reviewed the English literature on the association of retinal lesions with
      disseminated bacterial or candidal infection (DBCI). We found that 15 (19%) of
      the ICU patients had retinal lesions consistent with DBCI. Of these 15, 1 had
      clearly sepsis-related retinal lesions, while 13 (87%) had 1 or more systemic
      disease that could have explained their retinal findings (6 diabetic retinopathy;
      2 human immunodeficiency virus infection/acquired immunodeficiency syndrome
      (HIV/AIDS) retinopathy; 2 hypertensive retinopathy; 1 hemolytic uremic syndrome,
      and 1 leukemia). Multivariate analysis revealed that systemic disease (odds ratio
      8.37, 95% confidence intervals: 3.24-21.56) independently correlated with the
      presence of retinal lesions while DBCI, trauma, hyperalimentation, and
      transfusion of blood products were not independently predictive in any analysis.
      Twenty of the 180 (15%) candidemic patients had retinal lesions. Two (1%) had
      classic 3-dimensional white lesions with vitreal extension, and 5 (2.7%) had
      chorioretinal lesions without vitreal haziness. Notably, 10% of patients had
      superficial retinal hemorrhages and/or cotton wool spots that could have been due
      to either candidemia or a systemic disease (diabetes, hypertension, renal
      failure, closed head trauma). Concurrent bacteremia occurred in 3 of the 27
      patients with eye lesions. Retinal lesions resolved in a mean of 33 days. None of
      the patients had symptoms at the time of the retinal finding. We found 3 studies
      that prospectively assessed retinal lesions in bacteremic patients. The frequency
      of retinal lesions in these series varied from 12% to 26%, with the most common
      lesions being cotton wool spots followed by superficial retinal hemorrhages.
      White-centered hemorrhages were seen in about 15% +/- 2 of bacteremic patients.
      Five studies prospectively evaluated candidemic patients for Candida
      endophthalmitis. These studies observed rates from 0% to 78% for lesions
      consistent with candidal endophthalmitis. Most studies performed recently found
      that nonspecific lesions such as cotton wool spots or superficial retinal
      hemorrhages occurred with a frequency of 11% to 20%. The availability of less
      toxic antifungal agents, more frequent use of empirical therapy, and the trend to
      early treatment may be altering the frequency of this complication. Observation
      of a classic 3-dimensional retina-based vitreal inflammatory process is virtually
      diagnostic of endogenous endophthalmitis due to Candida spp., but such lesions
      are relatively uncommon. Conversely, nonspecific lesions that could be due to
      bacterial or candidal endophthalmitis (cotton wool spots, retinal hemorrhages,
      and Roth spots) are seen frequently. These lesions are most often due to an
      underlying systemic disease rather than an infection. Serial examinations provide
      the best evidence that a given lesion is due to an intercurrent infection. The
      current low rate of vitreal extension of retinal process appears to be due to the
      high rate of empirical or therapeutic use of antifungal agents in high-risk
      patient groups. Ophthalmoscopy should be performed in patients with known
      candidemia. However, ophthalmoscopic examination seems to have little value in
      assisting with the discovery of occult disseminated candidiasis or bacterial
      infection.

PMID- 12792307
TI  - Spectrum of paraneoplastic neurologic disorders in women with breast and
      gynecologic cancer.
AB  - We conducted the current review of the paraneoplastic neurologic syndromes (PNSs)
      associated with gynecologic and breast carcinomas to describe their clinical and
      immunologic characteristics and their relative frequency. We retrospectively
      reviewed 92 patients whose serum was sent to our laboratories to detect
      onconeural antibodies and who were diagnosed as having PNSs associated with
      breast or gynecologic tumors. PNSs were defined as "definitive" and "possible"
      (atypical PNS, no onconeural antibodies, and no improvement after tumor
      treatment). Forty-nine patients had breast and 43 had gynecologic cancer. Sixty
      three patients had onconeural antibodies (50 Yo-ab, 5 Hu-ab, 5 Ri-ab, and 3
      amphiphysin-ab). Cerebellar ataxia represented 57 (62%) of all PNSs and was
      associated with anti-Yo in 88%. All Yo-abnegative patients had breast cancer; 4
      of them had a mild cerebellar syndrome that improved after tumor treatment.
      Sensorypredominant neuropathies were present in 17 (18%) patients. Seven of them
      had Hu-ab (5) or amphiphysin-ab (2). Other PNSs were opsoclonus-myoclonus
      syndrome (4 cases, Ri-ab in 2), sensorimotor neuropathy (4 cases), paraneoplastic
      encephalomyelitis (4 cases, Ri-ab in 3), paraneoplastic retinopathy (2 cases),
      amyotrophic lateral sclerosis (2 cases), stiff-person syndrome (1 with
      amphiphysin-ab), and limbic encephalitis (1 case). All patients with gynecologic
      cancer presented definitive PNS, and onconeural antibodies were diagnosed in 93%
      of them. In contrast, 20% of PNSs associated with breast cancer were defined as
      possible and the incidence of onconeural antibodies was 51%, excluding the 2
      patients with paraneoplastic retinopathy in whom antiretinal antibodies were not
      analyzed. In patients with possible PNS, a coincidental association between the
      tumor and the neurologic disorder cannot be excluded.

PMID- 12792306
TI  - MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome,
      and Epstein syndrome are not distinct entities but represent a variable
      expression of a single illness.
AB  - May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome
      are autosomal dominant macrothrombocytopenias distinguished by different
      combinations of clinical and laboratory signs, such as sensorineural hearing
      loss, cataract, nephritis, and polymorphonuclear Dohle-like bodies. Mutations in
      the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have
      been identified in all these syndromes. To understand the role of the MYH9
      mutations, we report the molecular defects in 12 new cases, which together with
      our previous works represent a cohort of 19 families. Since no genotype-phenotype
      correlation was established, we performed an accurate clinical and biochemical re
      evaluation of patients. In addition to macrothrombocytopenia, an abnormal
      distribution of NMMHC-IIA within leukocytes was observed in all individuals,
      including those without Dohle-like bodies. Selective, high-tone hearing
      deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients
      initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney
      abnormalities, such as hematuria and proteinuria, affected not only patients
      referred as Fechtner syndrome and Epstein syndrome but also those referred as May
      Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude
      that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein
      syndrome are not distinct entities but rather a single disorder with a continuous
      clinical spectrum varying from mild macrothrombocytopenia with leukocyte
      inclusions to a severe form complicated by hearing loss, cataracts, and renal
      failure. For this new nosologic entity, we propose the term "MHY9-related
      disease," which better interprets the recent knowledge in this field and
      identifies all patients at risk of developing renal, hearing, or visual defects.

PMID- 12792308
TI  - Duplicate publication in otolaryngology: gaining insight into the problem.

PMID- 12792309
TI  - Duplicate publications in the otolaryngology literature.
AB  - OBJECTIVE/HYPOTHESIS: A duplicate publication duplicates other published work by
      the same author(s). The purpose of the study was to define the extent of this
      problem within the otolaryngology literature. STUDY DESIGN: Retrospective review
      of the literature. METHODS: Original articles published in Archives of
      Otolaryngology-Head and Neck Surgery and Laryngoscope in 1999 were reviewed using
      the OVID search engine. Titles and abstracts from English articles written by the
      same first, second, or last author were analyzed, and suspected publications were
      evaluated. Duplicate publications were classified as dual (identical data set and
      conclusions) or suspected dual (nearly identical data set and conclusions)
      publications. RESULTS: Of the 492 articles evaluated, 40 index articles were
      identified. These led to a total of 42 (8.5%) duplicate articles of which 27 were
      classified as dual and 15 as suspected dual publications. Approximately half of
      the duplicate publications were published by authors in the United States (55%).
      Duplicate articles usually appeared within 12 months of the each other (74%) and
      failed to cross-reference the earlier publication (83%). CONCLUSIONS: Journal
      editors have become aware of an increase in the number of duplicate publications
      in the medical literature. The incidence of duplicate publications in the
      otolaryngology literature appears to be similar to that in other specialties.

PMID- 12792310
TI  - Endoscopic surgery for juvenile angiofibroma: when and how.
AB  - OBJECTIVES/HYPOTHESIS: In recent years, the indications for endoscopic surgery of
      the sinonasal tract, originally introduced for the treatment of inflammatory
      diseases, have been expanded to include selected cases of benign and malignant
      neoplastic lesions. The aim of the present study was to establish the efficacy of
      endoscopic surgery in the management of small and intermediate-sized juvenile
      angiofibromas. STUDY DESIGN: Retrospective study. METHODS: We reviewed the
      clinical records and the preoperative and postoperative imaging studies of 15
      patients with juvenile angiofibroma who were treated with an endoscopic approach
      after embolization in the period from January 1994 to April 2000. All patients
      were prospectively followed by endoscopic and magnetic resonance imaging
      evaluations performed at regular intervals (every 4 months during the first year
      and, subsequently, every 6 months). RESULTS: According to a staging system
      reported in 1989, there were two patients with a type I, nine with a type II,
      three with a type IIIA, and one with a type IIIB juvenile angiofibroma.
      Angiography demonstrated that the vascular supply was strictly unilateral in 11
      patients and bilateral in 4. Intraoperative blood loss ranged from 80 to 600 mL
      (mean blood loss, 372 mL). During follow-up (range, 24-93 mo; mean follow-up, 50
      mo [SD +/- 19.9 mo]), only one patient presented a residual lesion on magnetic
      resonance imaging, which was 16 mm in diameter and was detected 24 months after
      surgery. CONCLUSIONS: The endoscopic approach is a safe and effective technique
      that allows removal of small and intermediate-sized juvenile angiofibromas
      (without extensive involvement of the infratemporal fossa and cavernous sinus)
      with a low morbidity. Advanced lesions are more appropriately treated by external
      approaches.

PMID- 12792311
TI  - Mesenchymal chondrosarcoma of the sinonasal tract: a clinicopathological study of
      13 cases with a review of the literature.
AB  - OBJECTIVES/HYPOTHESIS: Mesenchymal chondrosarcoma of the sinonasal tract is a
      rare, malignant tumor of extraskeletal origin. Isolated cases have been reported
      in the English literature, with no large series evaluating the
      clinicopathological aspects of these tumors. STUDY DESIGN: Retrospective review.
      METHODS: Thirteen patients with sinonasal mesenchymal chondrosarcoma were
      retrieved from the Otorhinolaryngologic-Head and Neck Registry of the Armed
      Forces Institute of Pathology. RESULTS: Nine women and 4 men (age range, 11 to 83
      y; mean age, 38.8 y) presented with nasal obstruction (n = 8), epistaxis (n = 7),
      or mass effect (n = 4), or a combination of these. No patients reported prior
      head and neck irradiation. The maxillary sinus was the most common site of
      involvement (n = 9), followed by the ethmoid sinuses (n = 7) and the nasal cavity
      (n = 5). Tumors had an overall mean size of 5.1 cm. Microscopically, the tumors
      displayed a small, blue, round cell morphology appearance arranged in a
      hemangiopericytoma-like pattern with foci of cartilaginous matrix. All cases were
      managed by surgery with adjuvant radiation therapy (n = 4) and/or chemotherapy (n
      = 3). The overall mean survival was 12.1 years, although five of six patients who
      developed local recurrences died of disease (mean survival, 6.5 y). Six patients
      were alive and disease free (mean survival, 17.3 y), and two patients were lost
      to follow-up. CONCLUSIONS: Mesenchymal chondrosarcoma of the sinonasal tract is
      an aggressive tumor with a predilection for young women. The pattern of growth
      and scarcity of cartilaginous matrix result in frequent misdiagnosis. Recurrence
      develops in approximately one-third of patients and seems to predict a poor
      prognosis. Aggressive, exenterative surgery combined with adjuvant therapy
      appears to yield the best clinical outcome.

PMID- 12792312
TI  - Branching of spiral ganglion neurites is induced by focal application of
      fibroblast growth factor-1.
AB  - OBJECTIVES/HYPOTHESIS: During the terminal innervation of the developing organ of
      Corti, fibroblast growth factor-1 (FGF-1) messenger RNA has been shown to be
      transiently expressed in the sensory epithelium of the rat, suggesting that this
      growth factor may contribute to developmental processes such as innervation and
      synaptogenesis of the inner and outer hair cells. In a previous study it has been
      demonstrated that exogenous FGF-1 supports rat spiral ganglion neurite extension
      in vitro, whereas a secreted form of FGF-1 produced by transfected fibrocytes
      induces neurite branching and targeting. STUDY DESIGN: Response of spiral
      ganglion neurites to FGF-1-coupled beads was compared with the response to
      noncoupled control beads. METHODS: Effects of multiple focal sources of FGF-1 to
      outgrowing spiral ganglion neurites were investigated on explants from postnatal
      day 4 rat spiral ganglion samples that were cultured in the presence of FGF-1
      covalently coupled to polybead microspheres. After fixation and
      immunocytochemical labeling of the explants the growth patterns of the extending
      neuronal processes were evaluated. RESULTS: When spiral ganglion neurites were
      observed near clusters of FGF-1 beads, they formed a plexus-like network
      characterized by significantly higher branching in the vicinity of the beads.
      However, fibers did not appear to terminate on the beads. Plexus-like formations
      were not seen at a distance from FGF-1 coupled beads or in the vicinity of
      control beads lacking FGF-1 on their surface. CONCLUSION: The results of the
      study indicate that spiral ganglion neurites branch in response to focal sources
      of FGF-1, suggesting an important role of this growth factor for hair cell
      innervation during the terminal development of the sensory epithelium.

PMID- 12792313
TI  - Clinical associations of serum antiendothelial cell antibodies in patients with
      sudden sensorineural hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: The role of antiendothelial cell antibodies in systemic
      vasculitis has been reported. The aim of the study was to define the clinical
      associations of serum antiendothelial cell antibodies in patients with sudden
      sensorineural hearing loss. STUDY DESIGN: A prospective study in patients with
      sudden sensorineural hearing loss. METHODS: Serum samples were taken from 59
      consecutive patients with sudden sensorineural hearing loss at time of
      presentation and from 28 normal control subjects. Indirect immunofluorescence
      assay was used to detect antiendothelial cell antibodies. RESULTS: The prevalence
      of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a
      statistically significant difference between patients and control subjects (P
      =.0004). Antiendothelial cell antibody positivity was significantly associated
      with absent recovery of hearing loss (P =.0020). CONCLUSIONS: The cytotoxicity to
      endothelial cells of the inner ear by antiendothelial cell antibody-positive sera
      might play a role in causing the stria vascularis damage in immune-mediated
      sudden sensorineural deafness. The appearance of antiendothelial cell antibody is
      related to the poor outcome of hearing loss, and its detection could be helpful
      in the selection of particular patients with sensorineural hearing loss for
      specific immunosuppressive treatments.

PMID- 12792314
TI  - Proximity of carotid canal wall to tympanic membrane: a human temporal bone
      study.
AB  - OBJECTIVE: The objective was to examine the possible risk of injury to the
      internal carotid artery during procedures in the middle ear, including
      myringotomy. STUDY DESIGN: Histopathological morphometric study of human temporal
      bones. METHODS: One hundred forty-two human temporal bone specimens obtained from
      92 individuals without any known ear disease were prepared for light microscopic
      study. Using 83 bones that were available for measurement, the thickness of the
      carotid canal wall (CCW), which is the medial wall of the bony portion of the
      eustachian tube, was measured. Using 15 bones selected for three-dimensional
      measurement, the closest distance from CCW to the anterior tympanic annulus was
      measured. Using all 142 temporal bone specimens, the CCW was examined to detect
      the presence of partial dehiscence. In one case, the images of CCW dehiscence and
      its surrounding structures were reconstructed by a personal computer. RESULTS:
      The thickness of the CCW was 0.00 to 0.73 mm (average thickness, 0.24 mm [+/-0.12
      mm]). The distance from the CCW to the anterior tympanic annulus was 1.8 to 8.1
      mm (average distance, 4.9 [+/-1.7 mm]). Dehiscence of CCW was observed in 7
      (4.9%) of 142 temporal bone specimens. The reconstructed image showed that the
      posterior half of the dehiscence of CCW could be seen from the external ear
      canal. CONCLUSIONS: The CCW was found to be extremely thin or even dehiscent in
      some cases, rendering the internal carotid artery vulnerable during transtympanic
      procedures. The study's findings emphasized the need for judicious care when
      operating in the anterior mesotympanum.

PMID- 12792316
TI  - Long-term hearing outcome in patients receiving intratympanic gentamicin for
      Meniere's disease.
AB  - OBJECTIVE: To determine the long-term hearing outcome in patients with
      intractable vertigo caused by unilateral Meniere's disease who were treated with
      intratympanic injection of gentamicin. STUDY DESIGN: The study was a longitudinal
      analysis of hearing and control of vertigo in patients with unilateral Meniere's
      disease who received intratympanic gentamicin. METHODS: Pure-tone thresholds and
      speech discrimination scores on audiometry were analyzed, along with the control
      of vertigo. Criteria described in 1995 by the American Academy of Otolaryngology
      Head and Neck Surgery (AAO-HNS) were used. Patients treated with intratympanic
      gentamicin had "definite" Meniere's disease and had intractable vertigo despite
      optimal medical therapy, no symptoms suggestive of Meniere's disease in the
      contralateral ear, and serviceable hearing in the contralateral ear. The study
      analyzed the outcomes of 34 patients for whom follow-up data were available for
      periods greater than 24 months after intratympanic gentamicin. RESULTS: Complete
      control of vertigo (AAOHNS Class A) was obtained in 90% of the patients. Profound
      sensorineural hearing loss occurred as a result of gentamicin injection in 1 of
      the 34 patients (3%). When data from all patients were grouped together, hearing
      was improved in 5 (15%), unchanged in 23 (68%), and worse in 6 (17%) patients.
      This distribution of hearing outcome is similar to that in patients whose
      symptoms of Meniere's disease were managed with medical measures. Recurrent
      vertigo developed in 10 patients (29%) at an interval of 4 to 15 months after
      initially complete control. Treatment with additional intratympanic injection(s)
      of gentamicin did not result in a change in hearing. CONCLUSION: The risk of
      hearing loss in patients treated with infrequent intratympanic injection(s) of
      gentamicin is low.

PMID- 12792315
TI  - Gene expression analysis of human middle ear cholesteatoma using complementary
      DNA arrays.
AB  - OBJECTIVE: To identify genes regulated in human cholesteatoma compared with
      normal skin tissue using complementary DNA arrays. STUDY DESIGN: In vitro
      analysis. METHODS: Eight cholesteatoma and retroauricular skin samples were
      obtained from the same patients during surgery. Upregulated and downregulated
      genes were highlighted using complementary DNA arrays for screening. Reverse
      transcriptase-polymerase chain reaction and immunohistochemical staining were
      performed to confirm the results of the complementary DNA array. RESULTS: Twelve
      genes were found to be induced or upregulated in cholesteatoma compared with skin
      samples. These included genes involved in cell proliferation and differentiation
      (eg, calgranulin A, calgranulin B, psoriasin, thymosin beta-10) and cell invasion
      (eg, cathepsin C, cathepsin D, cathepsin H). Analyses by means of reverse
      transcription-polymerase chain reaction showed enhanced expression of several
      genes including calgranulin A, calgranulin B, psoriasin, thymosin beta-10,
      cathepsin C, cathepsin D, and cathepsin H in cholesteatoma, supporting the
      findings from the gene array. In addition, it was verified by immunohistochemical
      analysis that the expressions of Calgranulin A, Calgranulin B, and Cathepsin D
      were mainly located in cholesteatoma epithelium. CONCLUSION: The observed
      alteration in gene expression may play a role in various mechanisms of
      pathogenesis in cholesteatoma.

PMID- 12792317
TI  - Chronic tinnitus resulting from head or neck injuries.
AB  - OBJECTIVES: The main objectives were 1) to determine the percentage of cases of
      chronic tinnitus in a specialized clinic that resulted from head or neck
      injuries; 2) to describe the characteristics of this population; and 3) to
      compare patients with head or neck trauma with patients whose tinnitus onset was
      not associated with head or neck injuries. STUDY DESIGN: Retrospective analysis
      of tinnitus clinic patient data. METHODS: Detailed questionnaires were mailed to
      2400 patients before their initial appointment at the Oregon Health and Science
      University Tinnitus Clinic (Portland, OR). All of the patients experienced and
      received treatment for chronic tinnitus. Patient data were entered into a
      database and later analyzed. RESULTS: Two hundred ninety-seven patients (214 male
      and 83 female patients) reported that their chronic tinnitus started as a result
      of head or neck injuries. Compared with patients whose tinnitus onset was not
      associated with trauma, patients with tinnitus associated with head or neck
      trauma were younger; had better hearing thresholds; experienced headaches more
      frequently; reported greater difficulties with concentration, memory, and
      thinking clearly; were more likely to experience current depression, but not
      lifetime depression; rated their tinnitus as louder on a 1-to-10 scale; matched
      their tinnitus to louder sounds on the right side; and had higher Tinnitus
      Severity Index scores. CONCLUSIONS: Tinnitus is a significant symptom that
      commonly occurs as a result of head or neck trauma. The fact that tinnitus
      resulting from head or neck injuries tends to be more severe (and is often
      accompanied by a greater number of co-symptoms) than tinnitus resulting from
      other causes should be taken into account by clinicians treating these patients.

PMID- 12792318
TI  - A randomized trial of the canalith repositioning procedure.
AB  - OBJECTIVE: To compare the effectiveness and complications of our adaptation of
      the canalith repositioning procedure (CRP) with the expectation treatment for
      benign paroxysmal positional vertigo. STUDY DESIGN: A randomized, controlled
      trial in the setting of a neurotological clinic in Thailand. METHODS: Fifty-eight
      patients with posterior benign paroxysmal positional vertigo were randomly
      assigned to treatment and control groups using a block of four. The treatment
      group was treated with the modified CRP technique until the nystagmus
      disappeared. A mastoid oscillator was not used, nor were any instructions given
      for patients after the maneuver. Both groups recorded the daily grading of
      symptoms and the amount of anti-vertiginous drugs (cinnarizine) taken. Objective
      and subjective assessments were made weekly until the nystagmus disappeared or
      until 4 weeks had passed since treatment began. RESULTS: The rates of
      effectiveness of CRP treatment and the control treatment for benign paroxysmal
      positional vertigo were 75.9% and 48.2%, respectively. There was a significant
      difference in the treatment outcomes of the CRP and control groups (P =.03). The
      CRP group used significantly fewer drugs than the control group (P =.001).
      Complications in the CRP group, such as lateral canalithiasis and fainting, were
      observed in 13.8% of the patients. CONCLUSIONS: The CRP was more effective than
      the expectation treatment for benign paroxysmal positional vertigo insofar as it
      provided faster recovery and required less dependence on medication.
      Complications of CRP were limited to 13.8% of patients.

PMID- 12792320
TI  - Autograft ossiculoplasty in cholesteatoma surgery: is it feasible?
AB  - OBJECTIVE: To investigate whether autologous ossicles can be safely used in
      ossicular reconstruction in cholesteatoma surgery after attempting cholesteatoma
      removal under the operating microscope. STUDY DESIGN: A prospective fine-section
      histological study of formalin-stored ossicles, harvested from cholesteatomatous
      ears, to evaluate for existence of residual cholesteatoma after surface disease
      clearance under the operating microscope. METHODS: One hundred four ossicles were
      harvested from 76 patients with cholesteatoma for the study. These malleus heads
      and includes were categorized into three groups: group 1, ossicles with retained
      shape and useful bulk, treated by microscopic stripping alone; group 2, ossicles
      with retained shape and useful bulk, treated by microscopic stripping and
      drilling; and group 3, badly eroded ossicles, treated by microscopic stripping
      alone. These treated ossicles were then subjected to 4 microm histopathological
      study. RESULTS: Residual disease was identified in 6 of the 104 ossicles.
      Residual disease was found only in badly eroded ossicles that are not suitable
      for reconstruction. All the usable ossicles were free of disease. CONCLUSIONS:
      Autologous ossicles that have retained body and bulk are safe to use for
      reconstruction after surface stripping under the operating microscope. Additional
      burring probably adds a further margin of safety.

PMID- 12792319
TI  - Development of a novel eighth-nerve intraneural auditory neuroprosthesis.
AB  - OBJECTIVES/HYPOTHESIS: Cochlear nerve stimulation using a linear array of
      electrodes, the cochlear implant, has become an accepted treatment for profound
      deafness. Major limitations of this technology are high threshold of stimulation,
      poor performance in a noisy background, cross-talk between electrodes,
      unsatisfactory channel selectivity, and variable reconstruction of frequency
      space. A novel auditory neuroprosthesis is proposed that is expected to overcome
      these problems by implanting an array of three-dimensional microelectrodes, the
      Utah Electrode Array, directly into the cochlear nerve. STUDY DESIGN: We have
      conducted acute, extending for up to 12 hours and semichronic, extending for up
      to 52 hours, electrophysiological experiments, radiologic and histologic studies
      in 12 cats. METHODS: The electrically evoked auditory brainstem response was used
      as a means to characterize the threshold, dynamic range, and stability of
      cochlear nerve stimulation through the implanted Utah Electrode Array
      neuroprosthesis. Plain film, computed tomographic, and histological studies were
      conducted to determine the result of the implant. RESULTS: The electrically
      evoked auditory brainstem response thresholds were approximately one to two
      orders of magnitude lower than those evoked with conventional cochlear implants.
      We were able to close the cochleostomy, bring the cat into normal anatomical
      position, and obtain stable electrically evoked auditory brainstem responses for
      up to 52 hours. Plain film and computed tomographic studies indicated that the
      Utah Electrode Array neuroprosthesis was in the intended position in the nerve.
      Histological studies did not reveal hemorrhage or significant damage to the
      nerve. CONCLUSION: Because the presented stimulation paradigm appears to
      significantly mitigate some of the problems of conventional cochlear implants, it
      may offer a new therapeutic approach to profound deafness.

PMID- 12792321
TI  - Technical refinements and precautions during ionomeric cement reconstruction of
      incus erosion during revision stapedectomy.
AB  - OBJECTIVE: The study describes the technical precautions and short-term hearing
      results of fast-setting ionomeric cement (SerenoCem) for managing incus erosion
      in revision stapedectomy. STUDY DESIGN: Observational and retrospective chart
      review. METHODS: Consecutive patients undergoing ionomeric cement incus
      reconstruction during revision stapedectomy had surgery on an ambulatory basis in
      a tertiary care referral center. Main outcome measures included technical
      details, precautions, and recommendations for handling this new material and 6
      week hearing outcomes comparing preoperative and postoperative air-conduction and
      bone-conduction thresholds. RESULTS: A small amount of ionomeric cement on the
      tip of otological picks applied to the incus remnant successfully reconstitutes
      the original length of the long process of the incus. In revision stapedectomy, a
      crimp-on prosthesis may be placed on the cement-lengthened incus. Six-week
      postoperative audiograms demonstrated significant closure of the air-bone gap in
      operated cases. Our experience in a failed case leads us to recommend that the
      setting time for the cement be increased to no less than 20 minutes as opposed to
      the manufacturer's recommendation of 10 minutes. Also, revision stapedectomy was
      more likely to be successful when the prosthesis was placed to the incus remnant
      and stabilized with cement, rather than placing the prosthesis on the cement
      itself. CONCLUSIONS: Ionomeric cement permits direct reconstruction of a
      pathologically shortened incus in revision stapedectomy. Surgeons must be aware
      of precaution and limitations of this new material. Preliminary results indicate
      significant hearing improvement with this technique when appropriate precautions
      are taken.

PMID- 12792322
TI  - Stapes prosthesis attachment: the effect of crimping on sound transfer in
      otosclerosis surgery.
AB  - OBJECTIVES/HYPOTHESIS: Although in stapes surgery successful hearing improvement
      may be achieved in the majority of patients, unsatisfactory closure of the air
      bone gap can be recorded. One of many reasons for unexpected failures of stapes
      surgery may be the insufficient crimping of a stapes prosthesis onto the incus.
      The objectives of the study were to assess the amount of sound transmission loss
      in response to the quality of prosthesis crimping and to identify a required loop
      attachment pattern to obtain good sound transmission results. STUDY DESIGN:
      Experimental. METHODS: A temporal bone model was developed to measure the sound
      transmission properties between incus and prosthesis on 17 fresh human temporal
      bones. The attachment of a titanium stapes piston was assessed without crimping,
      followed by loose crimping and tight fixation to the incus, using scanning laser
      Doppler interferometry, endoscopic photography, micro grinding technique, and
      scanning electron microscopy. An algorithm had to be developed to simulate
      acoustical stimulation using electromechanical stimulation. RESULTS: Optimal
      tight crimping of the stapes piston revealed consistent good sound transfer
      function ranging from 0 to 7 dB loss, and loss remained, on average, at 2 dB. The
      mean transmission losses for conditions of loose crimping and no crimping were
      surprisingly small (within 10 dB). However, these unusual crimping conditions
      allowed a wide range of losses up to 28 dB. A close coupling at least at two
      opposite points was obligatory to obtain consistently good results. CONCLUSIONS:
      Perfect hearing reconstruction necessitates ideal crimping of a prosthesis to
      obtain consistently good results. However, the final functional gain depends on
      many different intraoperative and postoperative factors.

PMID- 12792323
TI  - Ventricular dysphonia: clinical aspects and therapeutic options.
AB  - OBJECTIVE/HYPOTHESIS: Ventricular dysphonia, also known as dysphonia plica
      ventricularis, refers to the pathological interference of the false vocal folds
      during phonation. Despite its low incidence and prevalence, Vd is a well-known
      phenomenon in voice clinics. The present report reviews symptoms, etiology,
      diagnosis, and therapeutic options regarding this voice disorder. STUDY DESIGN:
      Literature review and case studies. METHODS: The literature pertaining to all
      clinical aspects of V(D) was reviewed to define diagnostic and therapeutic
      clinical decision making. RESULTS: Ventricular dysphonia is characterized by a
      typical rough, low-pitched voice quality resulting from false vocal fold
      vibration. Ventricular dysphonia may be compensatory when true vocal folds are
      affected (resection, paralysis). Noncompensatory types may be of habitual,
      psychoemotional, or idiopathic origin. Because perceptual symptoms may vary
      considerably, diagnosis should rely on a meticulous voice assessment, including
      laryngeal videostroboscopic, perceptual, aerodynamic, and acoustic evaluation.
      Various therapeutic approaches for the noncompensatory type of ventricular
      dysphonia may be considered: voice therapy, psychotherapy, anesthetic or
      botulinum toxin injections, or surgery. CONCLUSION: The study presents the state
      of the art with respect to ventricular dysphonia and may be helpful in diagnosis
      and therapeutic decision-making.

PMID- 12792324
TI  - Endoscopic removal of sinonasal inverted papilloma including endoscopic medial
      maxillectomy.
AB  - OBJECTIVES/HYPOTHESIS: Surgical excision is regarded as the treatment of choice
      for sinonasal inverted papilloma. Resection can be performed endoscopically or
      through an external approach. Debate exists about which approach to use. The
      study presents different endoscopic techniques for various tumor locations and
      reviews the results. STUDY DESIGN: A prospective study and an integrated
      literature review. METHODS: Seventeen consecutive patients with inverted
      papilloma who underwent endoscopic surgical excision, including medial
      maxillectomies and modified Lothrop procedures, were analyzed. Preoperative
      symptoms, computed tomography and magnetic resonance imaging findings, operative
      findings, tumor stage, and outcomes were recorded. RESULTS: Thirteen male and
      four female patients presented with inverted papilloma between December 1993 and
      October 2001. Nasal obstruction was the most common presenting symptom (50%).
      Sixty-five percent of tumors were either stage II or stage III. Endoscopic
      resection was the primary treatment in 14 patients. Of the three patients who
      were secondarily treated endoscopically, one had recurrence and was subsequently
      found to have focus of squamous cell carcinoma. The overall recurrence rate was
      6% and the incidence of malignancy was 6% (1 of 17). Recurrence rate for primary
      resections was zero (0 of 14). Five patients underwent endoscopic medial
      maxillectomies, and one patient with frontal sinus inverted papilloma was
      successfully treated with a modified endoscopic Lothrop procedure. CONCLUSIONS:
      Endoscopic sinus surgery is a viable treatment alternative for sinonasal inverted
      papilloma. Recurrence rates for primary treatment are comparable to external
      approaches. Close follow-up of patients is mandatory because recurrence may be
      associated with malignancy.

PMID- 12792325
TI  - Orbital complications in endoscopic sinus surgery using powered instrumentation.
AB  - OBJECTIVES/HYPOTHESIS: Powered dissection is increasingly used in endoscopic
      sinus surgery. Although it has certain clear advantages over conventional
      instrumentation, powered dissection also presents special liabilities. The
      objectives of the report are to highlight the special dangers of powered
      instrumentation near the orbit, to suggest techniques that might minimize these
      risks, and to review the management of orbital injuries. STUDY DESIGN: Case
      series. METHODS: A retrospective review was performed of patients who were
      referred to our institution with orbital injury complicating endoscopic sinus
      surgery in which powered instrumentation had been used. Patient demographics,
      status as revision or primary surgery, degree of intraoperative blood loss,
      indications for surgery, intraoperative findings, the complication sustained,
      time of recognition of the complication, immediate and delayed treatment, and
      clinical course were obtained from the clinical records. RESULTS: Three patients
      had medial rectus muscle injuries. In addition to the medial rectus injury, one
      patient also had blindness, probably from an orbital hemorrhage. One patient
      underwent orbital exploration in an unsuccessful attempt to reattach the ends of
      the medial rectus muscle. One patient had continuing diplopia, but declined
      orbital exploration or strabismus surgery. CONCLUSIONS: Intraoperative orbital
      complications that might be of minor consequence with conventional
      instrumentation can have dramatic sequelae when powered dissection is used.
      Special care must be exercised in using powered instrumentation.

PMID- 12792326
TI  - The management of idiopathic olfactory hallucinations: a study of two patients.
AB  - OBJECTIVES/HYPOTHESIS: Idiopathic olfactory hallucination is a rare condition. We
      report two cases of idiopathic olfactory hallucination and a review of the
      literature that relates to this condition. STUDY DESIGN: A retrospective case
      study of two patients with idiopathic olfactory hallucination. METHODS: Records
      of two patients were retrospectively reviewed. RESULTS: The diagnosis of
      idiopathic olfactory hallucination was confirmed after excluding any intranasal
      disease or any central nervous system disorder discernible by an
      electroencephalogram and magnetic resonance imaging. Both patients were
      successfully treated with sodium valproate. One patient stopped taking sodium
      valproate because of side effects, only for the symptoms to return, but these
      were then controlled by phenytoin sodium. The mean patient follow-up time was 3
      years 5 months. CONCLUSIONS: The symptoms of some cases of idiopathic olfactory
      hallucination may be controlled by sodium valproate or phenytoin sodium. We
      hypothesize that this disorder may be a central phenomenon attributable to
      reverberating circuits.

PMID- 12792327
TI  - Radiofrequency tonsil reduction: safety, morbidity, and efficacy.
AB  - OBJECTIVES: To evaluate the safety, morbidity, and efficacy of radiofrequency
      tissue volume reduction of tonsils using two different surgical techniques and to
      compare these two techniques with each other and with classic tonsillectomy.
      STUDY DESIGN: A nonrandomized retrospective review of tonsil reductions was made
      between 2000 and 2002 using in vivo studies associated with tonsil reduction and
      tonsillectomy performed either in the hospital operating room or in the
      outpatient treatment area. METHODS: We studied 150 patients and divided them into
      three main groups based on surgical technique. Group A consisted of 50
      consecutive patients who underwent tonsil "ablation," Group B contained another
      50 consecutive individuals who received tonsil "coblation," and Group C consisted
      of 50 patients who underwent classic tonsillectomy (cold dissection). Each group
      consisted of two subcategories of children (age range, 1-12 y) and adults (age
      range, 12-60 y) with chronic tonsillar hypertrophy. Most of the pediatric
      patients underwent adenoidectomy during the same surgical procedure. Indications
      for tonsillectomy were those listed by the American Academy of Otolaryngology
      Head and Neck Surgery. A retrospective chart review was used to assess
      procedures, safety, morbidity, and efficacy of tonsil reduction and
      tonsillectomy. Four specific end points of morbidity were investigated: pain,
      return to normal diet, return to normal activity, and use of pain medication.
      Efficacy of tonsillectomy was determined by the clinical observation of the
      remaining tonsillar tissue and compared with pretreatment photographs of the
      tonsils. RESULTS: There were no complications in any of the groups. Efficacy was
      assessed based on the mean tonsil reduction and was found to be 100% for
      tonsillectomy, 86% for the tonsil coblation technique, but only 53.6% for the
      ablation technique. Morbidity was minimal in groups A and B and significantly
      greater in Group C. The number of pain days, narcotic-use days, and days before
      return to normal diet and activity were greatly reduced in groups A and B when
      compared with classic tonsillectomy (group C). Pain levels on day 1 were less
      than 3 (on a scale of 1-10) in groups A and B. The number of pain days and
      narcotic-use days was less than 4 days in groups A and B. Similarly, most
      patients returned to solid diet and normal activity by day 4. Pain levels, number
      of narcotic-use days, and number of days to return to normal diet and activity
      were significantly higher for classic tonsillectomy. CONCLUSIONS: Tonsil
      coblation has distinct advantages when compared with tonsil ablation and standard
      tonsillectomy. Tonsil coblation resulted in greater than 86% elimination of
      tonsillar tissue in both children and adults. In most patients, pain levels were
      minimal and limited to the first 48 hours after surgery. Return to normal diet
      and activity was much earlier in the coblation group versus classic
      tonsillectomy.

PMID- 12792328
TI  - Impact of positron emission tomography on the initial staging and therapy in
      locoregional advanced squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: To evaluate the impact of 18F-fluoro-deoxy-glucose positron emission
      tomography after standard diagnostic workup in patients with advanced head and
      neck squamous cell carcinoma on staging and radiation treatment planning. STUDY
      DESIGN: Prospective controlled study. METHODS: Forty-eight patients (42 men and 6
      women; mean age, 61 y; age range, 35-85 y) with histologically confirmed,
      advanced-stage (any T, N> or =N2 or T> or =T3, any N) mucosal head and neck
      squamous cell carcinoma underwent positron emission tomography. The routine
      workup consisting of physical examination, panendoscopy, chest x-ray film, and
      contrast-enhanced high-resolution helical computed tomography scan (HRCT) was
      used for comparison. End points were the extent of lymph node disease, distant
      metastases, and second primary tumors. RESULTS: In 41 of 48 patients (85%) the
      lymph node findings between HRCT and positron emission tomography were
      concordant. In three patients positron emission tomography led to an upstaging of
      the tumor in its N category, and in four patients positron emission tomography
      underestimated lymph node involvement. Positron emission tomography revealed more
      difficulties in delineating lymph node metastases adjacent to the primary tumor
      than did HRCT, but was superior for the detection of distant and contralateral
      lymph node metastases. Positron emission tomography suggested distant metastatic
      lesions in 6 of 48 patients (13%). Cytological workup confirmed distant
      metastases in two (4%) and second primary tumors in another two patients (4%).
      Positron emission tomography results were false-positive in two (4%) patients
      because of inflammatory changes. CONCLUSIONS: Whole-body PET is able to assess
      lymph node involvement, distant metastases, and second primaries in a single
      study. Even after a routine clinical staging, positron emission tomography leads
      to a change of treatment in approximately 8% of patients.

PMID- 12792329
TI  - Detection of occult cervical micrometastases in patients with head and neck
      squamous cell cancer.
AB  - OBJECTIVE: The incidence of occult nodal metastases associated with head and neck
      squamous cell carcinoma (HNSCC) and the clinical significance of nodal
      micrometastases by cytokeratin immunohistochemical analysis are examined. STUDY
      DESIGN: In all, 1012 lymph nodes from 50 patients treated between 1992 and 2001
      at the University of Colorado Health Sciences Center (Denver, CO) were evaluated
      retrospectively for micrometastases. METHODS: Serial sectioning in 5-to 6-microm
      interval specimens stained either with hematoxylin and eosin (H&E) or
      immunostaining for cytokeratins using the monoclonal antibody cocktail AE1/AE3
      was performed in 21 N0, 11 N1, and 14 N2 patient cases. Cases that showed
      scattered cells with suspect staining qualities but without morphological
      features consistent with HNSCC were further evaluated by epithelial membrane
      antigen (EMA) immunohistochemical analysis. RESULTS: H&E-stained and cytokeratin
      stained sections revealed occult nodal micrometastases in 3.8% of N0 and 5% of N1
      cases. Overall, 26 micrometastases were identified in N0 and N1 patients, causing
      29% of N0 patients and 45% of N1 patients to be upstaged. Cytokeratin
      immunostaining detected micrometastases in eight cases that were negative on H&E
      serial sectioning. Serial sectioning by H&E alone identified three additional
      micrometastases. Negative EMA immunostaining confirmed the absence of malignant
      cells in lymph node sections that were equivocal on cytokeratin staining.
      CONCLUSIONS: The use of serial sectioning with H&E and cytokeratin
      immunohistochemical analysis increases the detection of micrometastases that are
      often elusive by routine processing in patients with HNSCC. Improved methods of
      detecting micrometastases may provide a basis for improved planning of
      postoperative therapy for patients already at risk for tumor recurrence.

PMID- 12792330
TI  - Functional outcomes after primary oropharyngeal cancer resection and
      reconstruction with the radial forearm free flap.
AB  - OBJECTIVE: To report prospectively collected aeromechanical, acoustical, and
      perceptual speech outcomes, as well as preliminary swallowing data, in patients
      having reconstruction with radial forearm free flaps after primary resection for
      oropharyngeal cancer. STUDY DESIGN: Prospective cohort study. METHODS:
      Acoustical, aeromechanical, and perceptual speech data and swallowing data were
      gathered at three evaluation times (preoperatively and before and after radiation
      therapy) for patients treated for oropharyngeal cancer by means of primary
      resection and reconstruction with a radial forearm free flap. Degree of
      involvement of the soft palate and base of tongue, along with reconstructive
      techniques, were entered as between-group factors in the analysis. RESULTS: There
      were no significant differences in speech intelligibility between the patient
      groups based on the degree of palate and tongue resected. However, patients with
      resections of half or more than half of the soft palate had significantly higher
      nasalance values and larger velopharyngeal orifice areas than individuals who had
      less than half of the soft palate resected. Significant within-subject
      differences were revealed across evaluation times for the dependent variables
      nasalance, velopharyngeal orifice area, and word intelligibility. Ninety-four
      percent of the patients were able to resume a normal or soft diet. There was a 6%
      incidence of aspiration in 128 swallows that were analyzed. The amount of base of
      tongue resected did not significantly affect any of the speech or swallowing
      parameters. CONCLUSIONS: Radial forearm free flaps are a good reconstructive
      option after oropharyngeal cancer extirpation. Our acoustic and aeromechanical
      results indicated that issues related to quality of the speech signal require
      further study for resections of half or more than half of the soft palate.

PMID- 12792331
TI  - Analysis of the relations between the shape of the reconstructed tongue and
      postoperative functions after subtotal or total glossectomy.
AB  - OBJECTIVES/HYPOTHESIS: For reconstruction after subtotal or total glossectomy,
      both preserving the larynx and maintaining postoperative swallowing and speech
      functions can greatly improve quality of life; however, postoperative functional
      results are often unstable. Our experiences suggest that insufficient flap volume
      in the oral area and postoperative prolapse of the preserved larynx affect
      postoperative function. The objective was to investigate the relations of the
      shape of the reconstructed tongue to postoperative swallowing and speech
      functions. STUDY DESIGN: The shape of the reconstructed tongue was classified on
      the basis of magnetic resonance and intraoral inspection as protuberant, semi
      protuberant, flat, or depressed. Speech intelligibility was evaluated, and body
      weight, which might affect the shape of the transferred flap, was measured before
      and after surgery. METHODS: Thirty patients who had undergone subtotal or total
      glossectomy and subsequent reconstruction were reviewed. RESULTS: We found that
      speech intelligibility (P <.001), food (P <.01), and deglutition (P <.003) scores
      were significantly lower in patients with flat or depressed tongues than in
      patients with semi-protuberant or protuberant tongues. Weight loss after surgery
      was significantly greater in patients with depressed tongues than in other
      patients (P <.013). Our results indicate that postoperative function is related
      to the shape of the reconstructed tongue. CONCLUSIONS: We suggest that 1) wider
      and thicker flaps, such as rectus abdominis musculocutaneous flaps, be used; 2)
      flaps be designed to be approximately 30% wider than the defect; 3) laryngeal
      suspension be used to prevent prolapse of the transferred flap; and 4) careful
      general management and sufficient nutrition are important in the early
      postoperative period.

PMID- 12792333
TI  - Digital microphotography: a simple solution.

PMID- 12792332
TI  - Voice quality after laser surgery or radiotherapy for T1a glottic carcinoma.
AB  - OBJECTIVE: To compare the effect on phonation of radiotherapy and endoscopic
      laser surgery for stage T1a glottic squamous cell carcinoma. STUDY DESIGN:
      Retrospective. METHODS: Patients treated for stage T1a glottic carcinoma from
      August 1994 to March 2000 and who had been followed for at least 1 year were
      candidates. Eight patients who underwent radiotherapy and 22 who underwent laser
      surgery were enrolled. Indirect laryngoscopy and stroboscopic examination were
      performed, and voice quality was analyzed using standard parameters. RESULTS:
      Maximum phonation time, average airflow rate, sound pressure level, and average
      fundamental frequency during unconditional phonation were similar after laser
      surgery and radiotherapy. However, compared with normal men who were 50 years of
      age or older, the average fundamental frequency was higher after laser surgery.
      CONCLUSIONS: Contrary to some reports, the voice quality is minimally affected by
      laser surgery for T1a glottic carcinoma, and outcome is similar to radiotherapy.
      The average fundamental frequency is higher than normal after laser surgery, but
      the effect on the quality of life was trivial.

PMID- 12792334
TI  - Cervical emphysema complicating tonsillectomy with argon beam coagulation.

PMID- 12792335
TI  - Comparison of anterior and posterior approaches in cervical spinal cord injuries.
AB  - This study reports the results of 52 patients with unstable cervical spine
      injuries and associated spinal cord injuries randomized to either anterior or
      posterior stabilization and fusion. All patients had achieved reduction and had
      unstable injuries that were thought to require surgical stabilization. Patients
      requiring a specific approach for either reduction or decompression were not
      included. Frankel grades and ASIA motor index scores were followed in each
      patient as well as fusion status, changes in alignment, and pain at final follow
      up. Neurologic improvement was noted in each group with no significant
      differences. In the anterior group, 70% improved at least 1 Frankel grade and 57%
      improved 1 Frankel grade in the posterior group. There were two nonunions in the
      anterior group (90% fusion) and none in the posterior group (100% fusion),
      although this was not statistically different. Seven patients in each group
      complained of pain at the final follow-up. There were no significant differences
      in fusion rates, alignment, neurologic recovery, or long-term complaints of pain
      in patients treated with either anterior or posterior fusion and instrumentation.

PMID- 12792336
TI  - Single-level fixation of flexion distraction injuries.
AB  - Flexion distraction injuries of the thoracic and lumbar spine can be stabilized
      with a short construct spanning one motion segment. This surgical technique has
      not been well accepted because of the paucity of published outcomes of patients
      treated in this manner. The current study is a cohort of patients who underwent a
      standardized posterior open reduction and single-level fixation for this injury
      pattern. Independent observation prospectively followed the cohort for a minimum
      of 20 months with functional and radiologic outcomes determined. A significant (p
      < 0.0001) correction of deformity was achieved, from a mean preoperative kyphosis
      of 10.1 degrees to a mean postoperative lordosis of 0.9 degrees. No loss of
      correction occurred. The mean Oswestry score was 11.5, with 88% of patients
      having minimal disability. This prospective study demonstrates the efficacy of
      posterior open reduction and single-level fixation of flexion distraction
      injuries.

PMID- 12792337
TI  - Documenting fusion following anterior cervical surgery: a comparison of
      roentgenogram versus two-dimensional computed tomographic findings.
AB  - Documentation of fusion following anterior cervical surgery may critically
      influence management strategies that can adversely affect outcome. Would two
      dimensional CT studies more accurately identify fusion following single-level
      anterior corpectomy with fusion compared with radiographic studies
      (plain/dynamic) alone? To answer this question, two radiologists, in a "blinded"
      fashion, separately read both radiographic and two-dimensional CT studies
      obtained 3 and 6 months following 46 single-level anterior corpectomy with
      fusion. Single-level anterior corpectomy with fusion used nonreversed iliac crest
      strut autografts and dynamic ABC plates (Aesculap, Tuttlingen, Germany).
      Following surgery, patients were immobilized in cervicothoracic orthoses, which
      were discontinued when fusion was confirmed. Patients were followed an average of
      3.2 years (minimum 2 years). Outcomes were measured with the Short Form-36
      questionnaire administered preoperatively, and 3, 6, and 12 months
      postoperatively. Three months after surgery, radiographs documented fusion in 38
      (83%) of 46 patients, whereas two-dimensional CTs confirmed fusion in only 23
      (50%) of 46 patients. Six months postoperatively, radiographs documented fusion
      in 44 (96%) of 46 patients, whereas only 32 (70%) of 46 patients were solidly
      fused on two-dimensional CT studies. Three and 6 months following single-level
      anterior corpectomy with fusion, two-dimensional CT scans more accurately
      confirmed fusion compared with radiographs alone.

PMID- 12792338
TI  - Atlantoaxial stabilization: clinical comparison of posterior cervical wiring
      technique with transarticular screw fixation.
AB  - Symptomatic atlantoaxial instability requires atlantoaxial stabilization. In this
      study the authors compared clinical, radiographic, and cervical outcome
      questionnaire results in 67 such patients who underwent 71 separate procedures.
      Thirty-eight patients had traditional posterior C1-C2 cervical wiring and halo
      vest immobilization (group 1), whereas 33 were alternatively managed with
      transarticular screw fixation without rigid external immobilization (group 2).
      Mean follow-up in group 1 was 53.2 months and mean follow-up in group 2 was 41.0
      months. Radiographic evaluation demonstrated seven pseudoarthroses and four
      fibrous unions in group 1, with six patients subsequently undergoing reoperation.
      There were no pseudoarthroses and two fibrous unions in the transarticular screw
      group (p = 0.015). In those that fused, >2-mm displacement occurred in six of the
      group 1 patients (p = 0.027). There was a trend toward fewer complications in
      group 2 patients (p = 0.085) with four complications, as compared with 12
      complications in group 1, including a 21% incidence of halo-vest-related
      complications. These results demonstrate the significant benefits of
      transarticular screw fixation over posterior cervical wiring techniques in the
      management of atlantoaxial instability.

PMID- 12792339
TI  - Prospective comparison of virtual fluoroscopy to fluoroscopy and plain
      radiographs for placement of lumbar pedicle screws.
AB  - Fluoroscopy-based frameless stereotactic systems provide feedback to the surgeon
      using virtual fluoroscopic images. The real-life accuracy of these virtual images
      has not been compared with traditional fluoroscopy in a clinical setting. We
      prospectively studied 23 consecutive cases. In two cases, registration errors
      precluded the use of virtual fluoroscopy. Pedicle probes placed with virtual
      fluoroscopic imaging were imaged with traditional fluoroscopy in the remaining 21
      cases. Position of the probes was judged to be ideal, acceptable but not ideal,
      or not acceptable based on the traditional fluoroscopic images. Virtual
      fluoroscopy was used to place probes in for 97 pedicles from L1 to the sacrum.
      Eighty-eight probes were judged to be in ideal position, eight were judged to be
      acceptable but not ideal, and one probe was judged to be in an unacceptable
      position. This probe was angled toward an adjacent disc space. Therefore, 96 of
      97 probes placed using virtual fluoroscopy were found to be in an acceptable
      position. The positive predictive value for acceptable screw placement with
      virtual fluoroscopy compared with traditional fluoroscopy was 99%. A probe placed
      with virtual fluoroscopic guidance will be judged to be in an acceptable position
      when imaged with traditional fluoroscopy 99% of the time.

PMID- 12792340
TI  - A prospective study on CT scan outcomes after conservative decompression surgery
      for lumbar spinal stenosis.
AB  - This is a prospective study analyzing CT scan imaging outcomes after conservative
      decompression in patients with lumbar spinal stenosis. Forty patients (18 males
      and 22 females) initially underwent a laminarthrectomy surgical procedure to
      decompress the central canal as well as the neuroforamina and nerve root canals
      while respecting the integrity of the neural arches, facet joints, and most
      muscle attachments. Morphologic features of preoperative CT scan images were
      compared with postoperative CT scans of the operative levels, obtained for 36
      patients (17 males and 19 females) after a minimum follow-up of 1 year (mean 1.7
      years). Successful surgical outcome was defined as an improvement in at least
      three of the following four criteria: self-reported pain on a visual analog
      scale, self-reported functional status measured by LBOS, reduction of pain while
      walking, and reduction of leg pain. Fifty-five percent of patients met the
      successful surgical outcome criteria, including 14 subjects who met all four
      success criteria. Overall, there was a statistically significant increase in the
      interfacet bony canal diameter of the operated levels (3.9 mm, p < 001). However,
      patients categorized as successful surgical outcomes had a substantially, but not
      significantly, lower interfacet canal diameter increase postsurgically (mean 3.41
      mm) in comparison with patients categorized as failures (mean postoperative
      increase 4.52 mm). Midsagittal canal diameters remained unchanged in the failure
      group but increased in the success group. The CT scan canal measures used in this
      study cannot be advocated for evaluation of outcome in conservative lumbar spinal
      canal decompression.

PMID- 12792341
TI  - A modified VSP screw: two-year experience.
AB  - A new pedicle screw was designed to address the insertion limitations of the
      existing VSP and TIMX screws. In the standard VSP insertion technique, the T
      handle wrench has an enlarged foot, which contacts the superior facet and
      interferes with countersinking the fixed nut. The hex of the machine screw may
      strip in hard bone. The hexagonal design of the fixed nut may make explantation
      difficult. The evolution of the VSP into the TIMX addresses some of these issues.
      However, the screw design still has problems. The tapered spacer extends beyond
      the diameter of the fixed nut and must be applied after the screw is inserted.
      The flattening of the machine thread requires rotational alignment of the screws
      before the plate can be inserted. The design does not allow for easy placement of
      the acorn nut. The modified VSP screw preserves the superior facet, allows for
      countersinking, permits application of the spacer prior to insertion, and
      facilitates application of the acorn nut. Rotational alignment of the screw is
      not required to accommodate the plate. The surgeon can save time and effort
      inserting and explanting the modified VSP screw.

PMID- 12792342
TI  - The effect of comprehensive group training on cross-sectional area, density, and
      strength of paraspinal muscles in patients sick-listed for subacute low back
      pain.
AB  - The effect of exercise on back muscle cross-sectional area (CSA), density, and
      strength was evaluated in patients sick-listed for subacute low back pain. Twenty
      four patients were randomized into an exercise (n = 11) or a control (n = 13)
      group. Patients in the exercise group followed a biweekly exercise protocol for
      15 weeks. Control patients received usual care. Muscle CSA and density were
      measured by computed tomography before and after intervention. Isokinetic test of
      back extensors was conducted simultaneously. Results showed a tendency to
      increased muscle CSA and density in patients in the exercise group, a significant
      decrease in muscle CSA at L4-L5 in control group patients, and a significant
      difference in change between groups in muscle CSA at L4-L5. Back extension
      strength increased in patients in the exercise group, but the improvement was not
      significant compared with control group patients. In conclusion, there was a
      tendency for reversal of muscle atrophy after exercise.

PMID- 12792343
TI  - "Pig Tail" technique in intradiscal electrothermal therapy.
AB  - To describe a new method of catheter insertion in intradiscal electrothermal
      therapy, which eliminates the need for reinsertion of the cannula and catheter
      from the contralateral side in those patients in whom optimal positioning is not
      achieved with the standard technique. This new technique has not been described
      before. In those patients in whom adequate catheter position cannot be achieved
      with the standard technique, instead of withdrawing the cannula after the initial
      treatment, we recommend rotating the cannula 180 degrees through its long axis.
      This will allow the catheter to hit the anterior anulus and deflect backwards
      toward the cannula. It can then be negotiated across the midline to adequately
      thermally treat the whole posterior anulus. We have performed our technique in 42
      consecutive patients in whom initial navigation was difficult. This new method
      proved to be simple and did not cause patients additional discomfort. The "pig
      tail" technique is safe and effective in intradiscal electrothermal therapy of
      those patients with difficult navigation. It avoids the need for second needle
      insertion, therefore avoiding the use of more local anesthesia, further
      discomfort for the patient, and additional radiographic exposure.

PMID- 12792344
TI  - Delayed presentation of septic arthritis of a lumbar facet joint after diagnostic
      facet joint injection.
AB  - We report the case of a 46-year-old, otherwise healthy, man with chronic lower
      back pain and no evidence of nerve root compression who underwent diagnostic
      facet joint injections to assist in establishing where his pain sources were
      located and to try to help his spinal rehabilitation program. He presented with a
      facet joint infection 2 months after injection, in a manner that was
      indistinguishable from an acute intervertebral disc herniation. The diagnosis was
      confirmed on magnetic resonance imaging, and he was successfully treated with
      surgical debridement and antibiotics. Septic arthritis of a lumbar facet joint
      with an associated paraspinal abscess is a rare complication of facet joint
      infiltration with only two similar cases reported in the literature. We propose
      that this diagnosis be considered in patients who have undergone diagnostic facet
      joint injection who subsequently deteriorate with back and leg pain without
      another apparent cause.

PMID- 12792345
TI  - Idiopathic spinal cord herniation in the thoracic spine as a cause of intractable
      leg pain: case report and review of the literature.
AB  - We recently experienced a case of idiopathic spinal cord herniation in the upper
      thoracic spine with development of severe unilateral leg pain: a 57-year-old man
      who had suffered from severe leg pain for about 15 years with lack of abnormality
      in his lumbar spine. On MRI of the thoracic spine, however, the spinal cord at T2
      T3 was bent forward with dilatation of the posterior subarachnoid space. In
      combination with the findings of computed tomographic myelography, we diagnosed
      idiopathic spinal cord herniation and performed a surgical treatment. Immediately
      after the operation, his leg pain disappeared. Therefore, we concluded that the
      cause of his leg pain was herniation of the thoracic spinal cord.

PMID- 12792346
TI  - Lower lumbar hyperextension fracture without paraplegia.
AB  - Lumbar shear injuries are a rare injury with few cases documented in the
      literature. They are the result of hyperextension combined with anteroposterior
      shearing forces. Those with near-complete displacement are usually associated
      with significant neurologic deficit. Presented here is a case of L4-L5 fracture
      dislocation with no neurologic loss.

PMID- 12792347
TI  - Idiopathic spinal cord herniation associated with a large erosive bone defect: a
      case report and review of the literature.
AB  - We report a case of idiopathic spinal cord herniation associated with a large
      bone defect. MRI and computed tomographic myelography revealed ventral deviation
      of the spinal cord and erosion of the vertebral body at T6-T7. Microscopic
      surgery revealed a dural defect. The etiology of this condition has not been
      clarified. In most previously reported cases, the peak portion of the herniation
      was around the intervertebral disc space. In addition, in our patient, it was
      hard to think that the intervertebral disc has become depressed due to the
      pressure exerted by the spinal cord. We considered that a certain condition of
      the intervertebral disc, such as herniation, was one of the causes of the dural
      defect, and cerebrospinal fluid pulsation pushed the spinal cord toward that
      portion, causing herniation.

PMID- 12792348
TI  - Plasma RNA quantification and HIV-1 divergent strains.
AB  - The diversity of HIV complicates viral load measurement for patient management
      and treatment monitoring. Numerous studies have shown that non-B group M variants
      can be underestimated and that group O strains are not detected by commercial
      tests. More recent versions of the kits used for previous studies have improved
      the quantification of non-B variants but are still unable to detect or correctly
      quantify group O strains. In this study, the authors evaluated the new Abbott LCx
      HIV RNA Quantitative viral load kit with a large collection of samples from
      Europe and central Africa. One hundred thirty-three group M samples, including 69
      from patients infected with non-B variants, and 70 group O samples were tested.
      The LCx system was compared with the Cobas Amplicor HIV-1 Monitor v1.5 test and
      with a quantitative real-time polymerase chain reaction method based on
      LightCycler technology. The LCx and Cobas tests had similar quantification ranges
      for group M samples and a high degree of linearity (r2 = 0.9582). The LCx method
      quantified group O variants (31 of the 48 patients were quantifiable) and gave
      values within the range of those obtained with the LightCycler assay. The two
      assays were sensitive but showed only moderate linearity (r2 = 0.6195), probably
      because of higher diversity of group O strains and the use of primers and probes
      in different regions. In conclusion, the authors showed that the LCx kit allowed
      quantification of the large group M diversity and group O variants.

PMID- 12792349
TI  - HIV-1 protease and reverse transcriptase mutation patterns responsible for
      discordances between genotypic drug resistance interpretation algorithms.
AB  - Several rules-based algorithms have been developed to interpret results of HIV-1
      genotypic resistance tests. To assess the concordance of these algorithms and to
      identify sequences causing interalgorithm discordances, we applied four publicly
      available algorithms to the sequences of isolates from 2,045 individuals in
      northern California. Drug resistance interpretations were classified as S for
      susceptible, I for intermediate, and R for resistant. Of 30,675 interpretations
      (2,045 sequences x 15 drugs), 4.4% were completely discordant, with at least one
      algorithm assigning an S and another an R; 29.2% were partially discordant, with
      at least one algorithm assigning an S and another an I, or at least one algorithm
      assigning an I and another an R; and 66.4% displayed complete concordance, with
      all four algorithms assigning the same interpretation. Discordances between
      nucleoside reverse transcriptase inhibitor interpretations usually resulted from
      several simple, frequently occurring mutational patterns. Discordances between
      protease inhibitor interpretations resulted from a larger number of more complex
      mutation patterns. Discordances between nonnucleoside reverse transcriptase
      inhibitor interpretations were uncommon and resulted from a small number of
      individual drug resistance mutations. Determining the clinical significance of
      these mutation patterns responsible for interalgorithm discordances will improve
      interalgorithm concordance and the accuracy of genotypic resistance
      interpretation.

PMID- 12792350
TI  - Extended treatment with tenofovir disoproxil fumarate in treatment-experienced
      HIV-1-infected patients: genotypic, phenotypic, and rebound analyses.
AB  - OBJECTIVE: To study the potential development of genotypic and phenotypic
      resistance to tenofovir disoproxil fumarate (tenofovir DF) when used as a part of
      a 96-week HIV-1 treatment regimen for antiretroviral treatment-experienced HIV
      infected patients. DESIGN AND METHODS: Clinical trial GS-98-902 was a placebo
      controlled, 48-week phase 2 study of three doses of tenofovir DF when added to
      stable antiretroviral therapy for 189 treatment-experienced HIV-infected patients
      (mean of 4.6 years of prior antiretroviral treatment; 94% had nucleoside reverse
      transcriptase [RT] inhibitor [NRTI]-associated mutations). There was a
      statistically significant reduction in the mean HIV-1 RNA level at week 24
      (average change in HIV-1 RNA level of -0.58 log(10) through week 24) with 300 mg
      of tenofovir DF once daily that was durable through week 48 (average change in
      HIV-1 RNA level of -0.62 log(10) through week 48). At week 48, 135 patients
      enrolled in an open-label, 48-week extension phase with 300 mg of tenofovir DF
      once daily added to their antiretroviral therapy. Genotypic analysis of plasma
      HIV-1 was performed for all patients after 96 weeks of study or upon early
      termination. Phenotypic analyses were performed at week 96 for patients with
      increases in HIV-1 RNA levels of > or =0.5 log(10) from week 48 to week 96.
      RESULTS: Genotypic results were obtained for 96 of 135 patients. NRTI-associated
      mutations developed in 41 (30%) of 135 patients from week 48 to week 96. Those
      mutations were primarily thymidine analog-associated mutations (33/41 patients)
      and developed while patients were receiving either stavudine or zidovudine. Two
      patients (1.5%) developed the K65R RT mutation (selected by tenofovir in vitro)
      but maintained HIV-1 suppression (-0.39 log(10)). These 96-week results were
      analogous to the 48-week results, in which 33% (n = 63) and 2.1% (n = 4) of
      patients developed thymidine analog-associated mutations or the K65R mutation,
      respectively. Although most patients maintained HIV-1 RNA suppression, an
      analysis of patients with increases in HIV-1 RNA levels of > or =0.5 log(10) (n =
      21) from week 48 to week 96 was performed. For eight of 21 patients, development
      of primary protease inhibitor-associated or non-NRTI-associated resistance
      mutations was likely responsible for the HIV-1 RNA rebound. The remaining
      patients developed either no mutation (n = 3) or a new NRTI-associated mutation
      (n = 10) and were analyzed phenotypically. No phenotypic changes for tenofovir
      were observed in these analyses. In addition, no new mutations potentially
      associated with tenofovir DF therapy were identified. Overall, patients had a
      similar reduction in HIV-1 RNA levels at week 96 and at week 48 compared with
      baseline (-0.55 and -0.60 log(10), respectively). CONCLUSIONS: Adding tenofovir
      DF (300 mg) to existing antiretroviral therapy for highly treatment-experienced
      patients with preexisting resistance mutations showed significant and durable
      reductions in HIV-1 RNA levels through week 96. Through 96 weeks of tenofovir DF
      therapy, 48 weeks of which included suboptimal doses of tenofovir DF, there was
      infrequent development of RT mutations associated with tenofovir DF therapy (K65R
      mutation, 3%), consistent with the durability of the observed HIV-1 RNA
      responses.

PMID- 12792352
TI  - Randomized, controlled, 48-week study of switching stavudine and/or protease
      inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected
      patients.
AB  - OBJECTIVE: HIV-1 protease inhibitors (versus no protease inhibitors) and
      stavudine (versus zidovudine) are independently associated with a higher risk of
      lipoatrophy in HIV-infected patients. We sought to determine whether the revision
      of stavudine and/or protease inhibitor-containing regimens to combivir/abacavir
      would result in prevention and/or reversibility of lipoatrophy in HIV-1-infected
      patients. DESIGN: The investigation was a prospective, randomized, controlled,
      open-label study. SUBJECTS: The subjects included 37 HIV-1-infected individuals
      with stable undetectable HIV-1 loads who were taking a regimen containing either
      stavudine or zidovudine with lamivudine and a protease inhibitor. INTERVENTION:
      Subjects were randomized to continue therapy or switch stavudine to zidovudine
      and protease inhibitor to abacavir, such that the universal switch regimen was
      combivir (zidovudine/lamivudine) and abacavir. MAIN OUTCOME MEASURES: Total body,
      leg, and arm fat mass was measured at baseline, 24 weeks, and 48 weeks using
      whole-body dual-energy x-ray absorptiometry. Single-cut L4 computed tomography
      and assays of multiple metabolic parameters were also performed. RESULTS: There
      was an average gain in fat mass of 0.009 kg/(leg.mo) in switch patients versus a
      loss of 0.010 kg/(leg.mo) in controls (p =.04, on-treatment analysis) over 48
      weeks. Significant arm fat restoration was observed in patients who switched
      regimens, with an average gain of 0.014 kg/(arm.mo) (p =.004), whereas controls
      did not have a significant change from baseline. Analyses of percentage changes
      in arm and leg fat masses showed similar findings. No significant effects on
      intraabdominal fat, blood lipid levels, glycemic indices, and lactate levels were
      detected, although most baseline mean values were normal in study subjects.
      Combivir/abacavir maintained virological control in all but one case, and three
      (13.6%) of 22 individuals had adverse reactions to abacavir therapy. CONCLUSIONS:
      A switch to combivir/abacavir therapy was associated with objective evidence of
      limb fat-sparing and fat restoration compared with continued treatment with
      stavudine and/or protease inhibitor.

PMID- 12792351
TI  - A 48-week, randomized, open-label comparison of three abacavir-based substitution
      approaches in the management of dyslipidemia and peripheral lipoatrophy.
AB  - BACKGROUND: The mechanisms by which dyslipidemia and lipoatrophy develop during
      antiretroviral therapy are not clear. No treatment of lipoatrophy is currently
      established. METHODS: This was an open-label randomized study of HIV-positive
      individuals on a first-line therapy containing stavudine (d4T) with either a
      protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)
      and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180
      mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients
      switched d4T to abacavir (ABC) (group 1), a PI or NNRTI to ABC (group 2), or d4T
      and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting
      blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomography
      (CT) scans for 48 weeks. RESULTS: Thirty patients were included, with 27
      completing 48 weeks of therapy. One ABC hypersensitivity reaction was the only
      serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4
      cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low
      density lipoprotein cholesterol improved significantly in groups 2 and 3.
      Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat
      mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3.
      Visceral adiposity (by CT scan) was unaffected in all groups. CONCLUSIONS:
      Abacavir represents a virologically effective replacement for d4T, PI, or NNRTI
      in persons on successful first-line therapy. Replacement of a PI or NNRTI with
      ABC leads to modest improvement in both cholesterol and triglycerides.
      Replacement of d4T with ABC leads to modest improvements in fat mass.

PMID- 12792353
TI  - Quantification of insulin-mediated glucose disposal in HIV-infected individuals:
      comparison of patients treated and untreated with protease inhibitors.
AB  - To describe the distribution of insulin sensitivity and glucose tolerance in HIV
      infected patients, the authors measured insulin-mediated glucose disposal (IMGD)
      in 51 subjects (24 protease inhibitor (PI)-treated subjects and 27 non-PI-treated
      subjects). IMGD was determined by measuring the steady-state plasma glucose
      (SSPG) concentration during the last 30 minutes of a 180-minute intravenous
      infusion of octreotide, glucose, and insulin. In addition, oral glucose tolerance
      testing was performed. SSPG concentrations varied six-fold in both groups, and
      the mean values +/- SEM did not differ between PI-treated and non-PI-treated
      groups (8.7 +/- 0.9 vs. 8.0 +/- 0.7 mmol/L, respectively). The mean fasting
      plasma glucose concentration +/- SEM was higher in the PI-treated subjects than
      in the non-PI-treated subjects (5.44 +/- 0.11 vs. 5.05 +/- 0.11 mmol/L,
      respectively; p =.01), whereas fasting plasma insulin concentrations did not
      differ. PI-treated patients also had significantly higher plasma glucose (p
      =.001) and insulin (p =.03) responses to the oral glucose challenge. However,
      whereas the incremental plasma glucose response during the first 30 minutes was
      significantly higher in PI-treated patients, the incremental insulin response in
      the two groups was identical. In conclusion, insulin sensitivity varies widely in
      HIV-infected patients irrespective of PI treatment, and the adverse effect of PIs
      on insulin sensitivity is likely to be of modest magnitude. Finally, PI treatment
      may have an inhibitory effect on insulin secretion.

PMID- 12792354
TI  - Randomized, controlled study of the effects of a short course of prednisone on
      the incidence of rash associated with nevirapine in patients infected with HIV-1.
AB  - OBJECTIVE: To examine the effect of 2 weeks of treatment with prednisone on the
      incidence of nevirapine-associated rash in HIV-1-infected patients receiving
      combination antiretroviral therapy. METHODS: This was a 24-week, prospective,
      randomized, open-label, international study. Patients were randomized to receive
      nevirapine plus open-label prednisone (40 mg once daily for 14 days) (n = 69) or
      nevirapine alone (n = 69). All patients received at least two other
      antiretroviral drugs. Nevirapine was administered at the lead-in dosage of 200 mg
      once daily. After the initial 2 weeks of the study, the nevirapine dosage was
      increased to 200 mg twice daily. RESULTS: During the first 6 weeks of treatment,
      rash was not reduced in the patients who received prednisone: prednisone
      treatment group, 23 (33%)/69; nonprednisone treatment group, 13 (19%)/69 (one
      tailed Fisher exact test for prednisone reducing the incidence of rash, p =.984).
      There tended to be more severe rashes (7% versus 1%, respectively) and more
      therapy discontinuations due to rash (16% versus 9%, respectively) in the
      prednisone treatment group than in the nonprednisone treatment group. Risk
      factors for rash included higher pretreatment CD4 cell count, lower HIV-1 RNA
      level, female sex, and higher trough nevirapine concentrations. The prednisone
      treatment group had a marked increase in the median CD4 cell count in the first 2
      weeks, which stabilized at a level similar to that in the nonprednisone treatment
      group. HIV-1 RNA responses were similar between the two groups. Treatment-naive
      patients had similar decreases in plasma HIV-1 RNA levels at week 24:
      approximately 2.3 log(10) copies/mL. CONCLUSIONS: This study demonstrated that 2
      weeks of concomitant therapy with prednisone does not decrease the occurrence of
      nevirapine-associated rash. The use of prednisone is not recommended to prevent
      rash in patients receiving nevirapine. Prednisone administration had no adverse
      effects on the virological responses or on CD4 cell count changes at 24 weeks.

PMID- 12792355
TI  - Identification of immunodominant epitopes in inactivated Tat-vaccinated healthy
      and HIV-1-infected volunteers.
AB  - We analyzed the epitopes and the molecular forms of Tat recognized by the
      antibodies raised by Tat-toxoid vaccination in both healthy and HIV-infected
      volunteers. Tat-toxoid-vaccinated healthy volunteer sera reacted predominantly
      with peptides covering amino acids 1 through 24 and 46 through 60, corresponding
      to the N-terminus and basic domains of Tat. In contrast, whereas all sera from
      vaccinated HIV-1-positive patients reacted with the N-terminus and (with a single
      exception) with the basic domain, most of these sera also recognized peptides
      encompassing distinct domains of Tat, particularly the C-terminus (79-86). The
      sera of vaccinated individuals recognized both monomeric and oligomeric forms of
      Tat 1 through 86 or of Tat 1 through 101 and also blocked the ability of cell
      released extracellular Tat to transactivate the HIV-1 LTR promoter. Synthetic Tat
      preincubated with sera from vaccinated individuals lost its functional activity
      as well. This is probably because of its inability to enter the cells as a result
      of immune complex formation with anti-Tat IgG. These data demonstrate that Tat
      toxoid vaccination induces an efficient antibody response blocking the functional
      activity of Tat.

PMID- 12792356
TI  - Delayed onset of pubertal development in children and adolescents with
      perinatally acquired HIV infection.
AB  - OBJECTIVE: To examine whether greater severity of HIV infection is associated
      with delayed initiation of pubertal development among perinatally HIV-infected
      children, and to compare sexual maturation of perinatally HIV-infected children
      with children in the general US population using the National Health and
      Nutrition Examination Survey III. METHODS: In a prospective cohort study, the
      authors studied 983 HIV-infected children aged 6 to 18 years, who had Tanner
      stage assessed on at least two occasions between 1995 and 2000. Analyses were
      conducted separately for girls and boys to identify factors associated with onset
      of puberty or adrenarche (progression beyond Tanner stage 1). RESULTS: Among
      children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%)
      girls and 144 of 434 (33%) boys entered puberty during the observation period. In
      multivariate longitudinal regression analyses adjusted for age, race/ethnicity,
      time interval between study visits, and other clinical factors, girls with severe
      immunosuppression (CD4% <15) were significantly less likely to enter adrenarche
      (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29-0.83) and puberty (OR,
      0.57; 95% CI, 0.33-0.96) compared with girls who were not immunosuppressed (CD4%
      > or =25). For boys, those with severe immunosuppression were significantly less
      likely to enter adrenarche (OR, 0.52; 95% CI, 0.28-0.96) and tended to be less
      likely to begin puberty (OR, 0.69; 95% CI, 0.39-1.22) compared with boys who were
      not immunosuppressed. Qualitative comparisons suggested that HIV-infected
      children may experience delayed puberty and adrenarche compared with similarly
      aged children in the general US population. CONCLUSIONS: Immunosuppression was
      associated with delayed pubertal onset in perinatally HIV-infected children.
      Further studies of perinatally HIV-infected and uninfected children are needed to
      better quantify the delay in pubertal onset and to compare the pace of pubertal
      maturation.

PMID- 12792357
TI  - Serum albumin is a powerful predictor of survival among HIV-1-infected women.
AB  - BACKGROUND: We previously reported that single measurements of albumin strongly
      predict survival in HIV-1-infected women independent of disease-specific markers.
      We now extend this to the use of serial measurements and single albumin values
      prior to initiation of highly active antiretroviral therapy. DESIGN: Prospective
      cohort study of 1941 women enrolled at six sites in the Women's Interagency HIV
      Study. RESULTS: Albumin fell 0.44 g/L/y in 1627 women who survived and at a
      faster rate in 397 who died (1.54 g/L/y; p <.01). In a time-dependent model
      adjusting for disease markers, the relative hazard (RH) was fivefold higher in
      patients with serum albumin <35 g/L compared with patients with serum albumin >42
      g/L. The RH of serum albumin <35 g/L in women with CD4+ lymphocyte counts > or
      =200 cells/micro L was 8.2 [95% CI: 4.2-15.8]) versus only 3.8 [95% CI: 2.4-6.1]
      in those with counts <200 cells/mm3. In a fixed-covariate Cox analysis of
      patients who started HAART during the study, albumin prior to HAART was
      associated with a higher RH (7.0 for albumin <35 g/L versus >42 g/L) than were
      other factors. CONCLUSION: Serum albumin is a strong independent predictor of
      mortality in HIV-1-infected women after adjustment for known disease markers and
      may be useful for clinical monitoring.

PMID- 12792358
TI  - Iron, haptoglobin phenotype, and HIV-1 viral load: a cross-sectional study among
      pregnant Zimbabwean women.
AB  - BACKGROUND: Viral load is a determinant of HIV-1 progression and transmission.
      Iron status and the phenotype of haptoglobin, a heme-binding acute phase
      reactant, may be determinants of viral load. We aimed to describe the effect of
      iron status, haptoglobin phenotype (Hp), and other predictors on HIV-1 viral
      load. METHODS: Based on a cross-sectional study among 1669 antenatal care
      attenders (22-35 weeks) in Zimbabwe, 526 (31.5%) were found to be HIV infected.
      The role of season, age, gravidity, gestational age, malaria parasitemia, Hp, and
      elevated serum alpha(1)-antichymotrypsin (ACT) as well as serum ferritin, folate,
      retinol, and beta-carotene on HIV viral load among the 526 HIV-infected women was
      assessed using multiple linear regression analysis. RESULTS: The distribution of
      Hp 1-1 (32%), Hp 2-1 (48%), and Hp 2-2 (20%) was not different from that of 53
      uninfected women. Mean viral load was 3.85 log(10) (95% CI: 3.77-3.93) genome
      equivalents (geq)/mL, ranging from 3.77 (95% CI: 3.64-3.90) geq/mL in women with
      Hp 1-1 to 4.05 (95% CI: 3.81-4.21) geq/mL in women with Hp 2-2. With elevated
      serum ACT controlled for, women with Hp 2-2 had viral loads twice (95% CI: 1.4
      4.0, p =.002) that of women with Hp 1-1, whereas those with serum ferritin <6
      micro g/L had viral loads less than one third (95% CI: 0.13-0.53, p =.013) that
      of women with serum ferritin >24 micro g/L. Viral loads were also higher in women
      enrolled in the early rainy season compared with the dry season, in gravidae 4+
      compared with gravidae 1 through 3, and in those with moderately elevated
      compared with low serum alpha(1)-antichymotrypsin, but neither age, gestational
      age, serum folate, serum retinol, nor serum beta-carotene were predictors.
      CONCLUSION: Storage iron, Hp 2-2, and elevated ACT are independent positive
      predictors of HIV-1 viral load. The positive relationship between serum ferritin
      and viral load was not the result of an acute phase response or iron accumulation
      with advanced HIV infection. A possible detrimental role of iron in HIV infection
      would have serious public health implications.

PMID- 12792360
TI  - HIV risk reduction in a cohort of injecting drug users in Bangkok, Thailand.
AB  - OBJECTIVE: To determine changes in risk behavior in relation to study
      participation among injecting drug users (IDUs) in Bangkok, Thailand. METHODS:
      During 1995-1996, 1,209 HIV-seronegative IDUs were recruited from Bangkok
      Metropolitan Administration drug abuse treatment programs to participate in a
      prospective cohort study. Study visits occurred every 4 months, at which the
      participants underwent an interview to assess risk behavior and HIV counseling
      and testing. Eight hundred nine of the IDUs were considered "long-term"
      participants, who remained in the study through at least the first four scheduled
      follow-up visits (16 months). Injection risk behavior at each study visit was
      measured on a four-point scale strongly associated with incident HIV infections
      in the cohort. Individual regression slopes were used to assess changes in
      injection risk behavior (risk increase, no change, or risk reduction). RESULTS:
      Of the 806 long-term study participants, 79% showed declines, 4% showed no
      change, and 17% showed increases in injection risk behavior. The percentage of
      participants in the highest-risk category (injecting daily or more frequently and
      sharing needles and syringes) declined from 42% at baseline to 3% at the final
      follow-up visit. Being in methadone maintenance treatment was associated with
      stable low rates of injection risk behavior, while recruitment from the 45-day
      detoxification treatment was associated with reductions in injection risk
      behavior. The risk reduction was independent of decline in risk behavior among
      IDUs in the community at large. CONCLUSIONS: Participation in this cohort study
      was associated with substantial declines in injection risk behavior. This
      information is important in the evaluation of possible adverse behavioral effects
      of participation in future preventive HIV vaccine trials including IDUs,
      particularly in developing country settings.

PMID- 12792361
TI  - Low socioeconomic status is associated with a higher rate of death in the era of
      highly active antiretroviral therapy, San Francisco.
AB  - Highly active antiretroviral therapy (HAART) has dramatically improved survival
      after AIDS. The benefits of HAART have not been equally realized for all
      communities, however. We characterize the association of socioeconomic status
      (SES) with survival after AIDS diagnosis in San Francisco in the period before
      (1980-1995) and after (1996 - 2001) the wider use of HAART. Using citywide
      surveillance data, we examined differences in survival after AIDS diagnosis by
      neighborhood household income using Kaplan-Meier survival analysis and Cox
      proportional hazards analysis to adjust for significant covariates. Residing in
      higher SES neighborhoods significantly predicted better survival after AIDS from
      1996 to 2001 (hazard ratio = 0.92 per $10,000 increase in neighborhood household
      income, 95% CI: 0.85-0.99) after adjusting for CD4 count at diagnosis, age, and
      injection drug user status. Persons living in poorer neighborhoods were less
      likely to use HAART at any time in the past compared with persons in wealthier
      neighborhoods. Moreover, no association between survival and neighborhood SES was
      evident in the era prior to the wide use of HAART. Finally, the difference in
      survival by neighborhood income level disappeared after controlling for the use
      of HAART, suggesting that use of or access to treatment explained the
      association. From 1996 to 2001, survival with AIDS was worse for people living in
      poorer neighborhoods compared with those living in wealthier neighborhoods of San
      Francisco as a result of unequal access to or use of HAART.

PMID- 12792359
TI  - HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative
      Treatment Study.
AB  - HIV risk was evaluated among 487 cocaine-dependent patients recruited from five
      treatment programs in a trial that examined the efficacy of four outpatient-based
      psychosocial treatments. Treatments were offered two to three times per week for
      6 months and consisted of group drug counseling (GDC) or group counseling plus
      individual drug counseling (IDC), cognitive therapy (CT), or supportive
      expressive therapy (SE). The average patient had used cocaine for 7 years, with
      10 days of use in the last month. Crack smoking was the main route in 79%, and
      HIV risk was mainly due to multiple partners and unprotected sex. Treatment was
      associated with a decrease in cocaine use from an average of 10 days per month at
      baseline to 1 day per month at 6 months. Reduction in cocaine use was associated
      with an average 40% decrease in HIV risk across all treatment, gender, and ethnic
      groups, mainly as a result of fewer sexual partners and less unprotected sex. The
      combination of IDC and GDC was associated with an equal or even greater reduction
      in HIV risk than the other treatment conditions and thus shows promise as an
      effective HIV prevention strategy, at least for some patients.

PMID- 12792362
TI  - Combination antiretroviral therapy and improvements in mental health: results
      from a nationally representative sample of persons undergoing care for HIV in the
      United States.
AB  - OBJECTIVE: To test whether mental health improvements observed in a nationally
      representative sample of 2466 HIV+ persons receiving care in the United States
      during the dissemination of combination antiretroviral therapy (ART) is a result
      of global optimism or directly related to treatment. ANALYSIS: Data were analyzed
      by means of a linear regression model of the change in psychiatric symptoms from
      baseline (January 1996-April 1997) to the first follow-up interview approximately
      8 months later as a function of changes in CD4+ counts, opportunistic infection
      treatments, and HIV physical symptoms in the overall sample and separately in
      participants who maintained ART, initiated ART, never received ART, or
      transitioned to a less recommended regimen during the study period. RESULTS: The
      reduction in psychiatric symptoms was comparable across all treatment groups (p
      >.05), suggesting a global effect. In patients who initiated or maintained ART,
      fewer psychiatric symptoms were significantly related to higher CD4+ and fewer
      opportunistic infection treatments and HIV symptoms, however, suggesting a
      treatment effect. CONCLUSION: ART appears to be responsible for both a treatment
      specific and global improvement in the mental health of HIV+ patients, possibly
      through the promise of extended survival and a better quality of life.

PMID- 12792363
TI  - Antiretroviral treatment and advanced age: epidemiologic, laboratory, and
      clinical features in the elderly.

PMID- 12792364
TI  - Effect of protease inhibitors on apolipoprotein B levels and plasma lipid profile
      in HIV-1-infected patients on highly active antiretroviral therapy.

PMID- 12792365
TI  - Screening subtle HIV-related cognitive dysfunction: the clinical utility of the
      HIV dementia scale.

PMID- 12792367
TI  - Uncontrolled herpes simplex virus-2 as a cofactor in HIV transmission.

PMID- 12792366
TI  - Efavirenz-based regimen as treatment of advanced AIDS with cryptococcal
      meningitis.

PMID- 12792369
TI  - Patients older than 65 are hospitals' "core business".

PMID- 12792370
TI  - Test your knowledge: fluids and electrolytes.
AB  - The CRNI Certification Examination consists of 200 multiple-choice questions
      covering the nine core content areas of infusion nursing: Technology and Clinical
      Applications, Fluid and Electrolyte Balance, Pharmacology, Infection Control,
      Pediatrics, Transfusion Therapy, Antineoplastic Therapy, Parenteral Nutrition,
      and Quality Assurance. The review questions provided below are modeled on the
      CRNI exam and are intended to help exam candidates test their knowledge of
      infusion therapy practice. This special section is a regular addition to the
      Journal of Infusion Nursing, with each edition focusing on a single content area.

PMID- 12792371
TI  - The elderly patient at risk.
AB  - As the baby-boom generation turn age 65, it is important that nurses are informed
      about the unique problems of the elderly patient, particularly because the
      elderly represent the highest percentage of clients in hospitals, homecare, and
      long-term and subacute nursing facilities. Infusion nurses, particularly those in
      homecare, are in a pivotal position to proactively identify acute illness at an
      early stage and thereby improve outcomes in this vulnerable population. To do
      this, infusion nurses must understand the normal changes that come with aging,
      the profile of the elderly patient at greatest risk for poor outcomes, and the
      often-atypical presentation of illness. Additionally, infusion nurses must be
      informed about tools used to assess and monitor the patient's status. Finally,
      infusion nurses must understand the increased potential for iatrogenesis in the
      elderly and provide proactive interventions to avert its occurrence to improve
      quality of life and outcomes for this population.

PMID- 12792372
TI  - Parenteral hydration and nutrition in the geriatric patient: clinical and ethical
      issues.
AB  - A common ethical and legal issue in elder care involves the decision to withhold
      or withdraw parenteral hydration and nutrition (PHN) at the end of life and in
      the terminal stage of dementia. The aging of the population will impact the
      frequency with which nurses face this situation in their practices and with their
      families. The ethical, legal, and clinical issues involving PHN discussed in this
      article will assist the nurse in his or her practice.

PMID- 12792373
TI  - Geriatric assessment and management protocols: issues for home infusion therapy
      providers.
AB  - The accurate assessment of patients' health, functional abilities, and
      sociobehavioral status is essential for providing quality, cost-effective
      infusion services to home-based elders. Baseline and ongoing assessment
      identifies serious current, emerging, and potential problems, and facilitates
      interventions to prevent significant comorbidities and premature mortality. Three
      types of assessment (screening, intermediate or evaluation, and comprehensive)
      have been used successfully with geriatric populations across a variety of
      settings to improve patient outcomes. Further, Medicare now requires the
      completion of an OASIS assessment for the reimbursement of home health services
      to all seniors. Geriatric assessment has been found to improve care quality and
      cost effectiveness, but protocol development and evaluation can be challenging.
      Home infusion therapy providers, encouraged to implement and evaluate evidence
      based assessment and management protocols, question the usefulness of these
      protocols, especially for short-term geriatric patients. Research, education, and
      policy strategies can be used to overcome the many barriers to developing
      quality, cost-effective assessment and management protocols for elderly home
      infusion therapy recipients.

PMID- 12792374
TI  - Pain management in elderly adults.
AB  - Pain is a common experience for many elderly adults that has negative
      consequences for their health, functioning, and quality of life. Effective pain
      management requires thorough assessment, appropriate intervention, and systematic
      reassessment. This article will discuss strategies for assessing and measuring
      pain in elderly adults, as well as barriers to effective pain assessment. Pain
      treatment strategies, including both pharmacological and non-pharmacological
      approaches will also be covered and special considerations for administering
      medications to elderly adults will be highlighted.

PMID- 12792375
TI  - Polypharmacy and the elderly.
AB  - Polypharmacy is the concurrent use of several different medications used by the
      same individual, which in some cases can lead to drug-drug interactions. Elderly
      patients often are faced with polypharmacy when they have multiple disease
      processes. Declining organ function, as part of the normal aging process, adds to
      the problem of adverse drug effects in this population. To minimize polypharmacy,
      prescribers aim to treat multiple disease conditions with a single agent if
      possible. Pharmacists can often help in drug selection, if given a set of
      criteria. This article is intended to help infusion professionals provide safe
      medication treatment by understanding how aging organ systems and medications
      affect the elderly.

PMID- 12792376
TI  - Early nutritional screening of older adults: review of nutritional support.
AB  - Protein-energy malnutrition and its consequences can have considerable impact on
      the quality of life of the elderly. Healthcare providers working with older
      adults are challenged to recognize individuals at risk for undernutrition and to
      initiate early nutritional assessment and intervention strategies to prevent
      malnutrition. In so doing, they can assist in improving the quality of life for
      the older adult and decrease healthcare costs associated with serious outcomes of
      malnutrition. Current knowledge about the nutritional needs of the elderly,
      definition of malnutrition, age-related risk factors, and causes of malnutrition
      in the elderly are presented in this article. A practical approach to preventing
      the occurrence of malnutrition is suggested through the use of a quick and easy
      nutritional screening assessment tool, the Mini Nutritional Assessment (MNA).
      Recommendations for specialized nutritional support, as well as its role in wound
      healing and immune enhancement, are discussed. Where available, scientific data
      supporting its use are included.

PMID- 12792377
TI  - Attitudes of pediatricians regarding influenza self-immunization: a survey in a
      Swiss university children's hospital.
AB  - OBJECTIVE: To assess the attitude toward influenza immunization of doctors among
      physicians in our hospital. METHODS: A self-administered questionnaire survey was
      performed in a voluntary and anonymous manner in early 2002 after influenza
      immunization for employees with patient contact had been promoted in the fall of
      2001. Physicians were asked whether they had been immunized or not and which of
      the following reason(s) for doing so applied to them: to protect themselves; to
      protect their patients; to set a positive example. Solicited reasons for decline:
      not convinced about necessity; not convinced about efficacy; concerns about side
      effects; negative attitude toward the immunization initiative; fear of injection.
      RESULTS: Questionnaires were sent to 90 pediatricians and returned by 46 (98%) of
      47 immunized and 25 (58%) of 43 unimmunized participants. Self-protection and
      protection of patients had been equally important reasons for acceptance (87%
      each); 46% wanted to set a positive example for their patients by being immunized
      themselves. Unimmunized physicians expressed doubts about necessity (56%),
      efficacy (32%) and concerns about side effects (24%). Of immunized physicians 98%
      considered reimmunization for the next season as did 60% of those currently
      unimmunized. CONCLUSIONS: Prevailing misconceptions indicate that increased
      educational efforts are necessary to improve acceptance of influenza vaccine in
      our institution.

PMID- 12792378
TI  - A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in
      young infants.
AB  - BACKGROUND: Parainfluenza type 3 virus (PIV-3) infections cause lower respiratory
      tract illness in children throughout the world. A licensed PIV-3 vaccine is not
      yet available. METHODS: A live attenuated cold-adapted (ca) and temperature
      sensitive (ts) PIV-3 vaccine, designated cp-45, was evaluated sequentially in
      open label studies in 20 adults and in placebo-controlled, double blind studies
      in 24 PIV-3-seropositive children, 52 PIV-3-seronegative infants and children and
      49 infants 1 to 2 months old. A single dose of this intranasal vaccine was
      evaluated in adults [106 plaque-forming units (pfu)] and seropositive children,
      and 104 and 105 pfu were evaluated in seronegative children. In the infant study,
      two 104 pfu doses of vaccine were administered at 1- or 3-month intervals.
      Safety, infectivity, immunogenicity and phenotypic stability of the vaccine were
      evaluated in all cohorts. RESULTS: The cp-45 vaccine was well-tolerated in all
      age groups and infected 94% of vaccinated seronegative children and 94% of
      vaccinated infants. Although immunization with the first dose of cp-45 diminished
      the replication of a second dose in all infants, those immunized after 3 months
      shed vaccine virus more frequently than those immunized after 1 month (62% vs.
      24%, respectively). Antibody responses to PIV-3 were readily detected in
      seronegative children with a variety of assays; however, the IgA response to the
      viral hemagglutinin-neuraminidase was the best measure of immunogenicity in young
      infants. Of 109 vaccine virus specimens recovered from nasal washes, 98 were ts
      and 11 were temperature-sensitive intermediate (tsi) viruses, with pinpoint
      plaques visible at 40 degrees C. tsi viruses appeared transiently at the time of
      peak viral replication, represented a very small proportion of the total virus
      shed and were not associated with changes in clinical status. ca revertants were
      not detected. CONCLUSIONS: The cp-45 vaccine is appropriately attenuated and
      immunogenic in infants as young as 1 month of age. Further development of this
      vaccine is warranted.

PMID- 12792379
TI  - Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute
      otitis media in children.
AB  - BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first
      line therapy of acute otitis media (AOM) in geographic areas where drug-resistant
      Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy
      of high dose amoxicillin treatment for AOM is limited. OBJECTIVES: To evaluate
      the bacteriologic and clinical efficacy of high dose amoxicillin as first line
      therapy in AOM. METHODS: In a prospective study 50 culture-positive patients ages
      3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose
      amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were
      administered 72 h before enrollment. Twenty-four (48%) patients presented with
      their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at
      enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures
      were obtained if clinical relapse occurred. Bacteriologic failure was defined by
      positive cultures on Days 4 to 6 and clinical failure by no change or worsening
      of AOM signs and symptoms and requirement for additional antibiotics during
      therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2.
      Susceptibility to penicillin and amoxicillin was measured by E-test. RESULTS:
      Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38),
      Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella
      catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin
      (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or =
      2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase
      producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%)
      pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative
      H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S.
      pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were
      isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1
      beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In
      total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6
      (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H.
      influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta
      lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days
      4 to 6. CONCLUSIONS: The predominant pathogens isolated from children with AOM
      failing high dose amoxicillin therapy were beta-lactamase-producing organisms.
      Because its overall clinical efficacy is good, high dose amoxicillin is still an
      appropriate choice as first line empiric therapy for AOM, followed by a beta
      lactamase-stable drug in the event of failure.

PMID- 12792380
TI  - Streptococcus pneumoniae-related illnesses in young children: secular trends and
      regional variation.
AB  - BACKGROUND: Children <2 years old have been targeted for routine pneumococcal
      conjugate vaccine. Laboratory-confirmed illnesses represent a minority of all
      medical care utilization for pneumococcal disease. OBJECTIVES: To evaluate trends
      in medical care utilization for Streptococcus pneumoniae-related illnesses before
      introduction of pneumococcal conjugate vaccine (1995 to 1999) and to evaluate
      regional variation in utilization. METHOD: Retrospective cohort analysis with the
      use of computerized billing data of children <2 years old enrolled in Tennessee
      (Medicaid program) and the Rochester, NY area (commercial and Medicaid managed
      care plans). Secular trends (1995 to 1999) analysis included 316 519 person-years
      in Tennessee Medicaid. Regional variation (1998 to 1999) analysis included 130
      525 person-years in Tennessee and 26 140 and 3184 person-years in commercial and
      Medicaid plans, respectively, in the Rochester, NY area. RESULTS: From 1995 to
      1999 in Tennessee, the net increase in medical care visits was 12% for
      pneumococcal and nonspecific pneumonia and invasive disease, 11% for otitis media
      and 11% for other acute respiratory conditions. Analysis of trends indicated that
      a significant vaccine effect could be detected if utilization rates declined by
      32, 9 and 21%, respectively. In the Tennessee Medicaid population, rates of
      pneumococcal and nonspecific pneumonia and invasive disease were 60% higher than
      in either the New York Medicaid or the commercial populations. Children with
      commercial insurance had the highest medical care utilization for otitis media.
      CONCLUSIONS: Geographic variation and large population differences in medical
      care utilization among children < 2 years old in three study populations suggest
      that the benefits of vaccination may vary by region and by population. In the
      Tennessee Medicaid population, temporal trends and year-to-year variability of
      pneumococcal-related outcomes were observed from 1995 to 1999. In this population
      a 10% decline in otitis media visits after the introduction of pneumococcal
      conjugate vaccine could be detected by trend analysis.

PMID- 12792381
TI  - Neonatal meningococcal disease in the United States, 1990 to 1999.
AB  - BACKGROUND: Although neonatal bacterial meningitis is common, the rate of
      invasive meningococcal disease in the United States among children < or =30 days
      old has not been defined. Most relevant literature consists of case reports or
      case series, which note high case-fatality ratios but do not describe the overall
      burden of disease. METHODS: We used active, population-based surveillance data
      from the Active Bacterial Core Surveillance program to estimate the incidence of
      neonatal meningococcal disease in the United States from 1990 to 1999. A case of
      neonatal meningococcal disease was defined as isolation of Neisseria meningitidis
      from a normally sterile site in a resident of the surveillance area < or =30 days
      of age. RESULTS: The median annual number of neonates under surveillance was 25
      900. Between 1990 and 1999, 22 cases of neonatal meningococcal disease were
      identified. Three (14%) patients died. The average annual incidence was 9 per 100
      000. CONCLUSIONS: The rate of neonatal meningococcal disease in the United States
      is higher than previous estimates. Meningococcal disease is uncommon in neonates,
      but its rate is similar to that of meningococcal disease in 6- to 23-month-old
      children.

PMID- 12792382
TI  - Reduction in perinatal transmission and mortality from human immunodeficiency
      virus after intervention with zidovudine in Barbados.
AB  - OBJECTIVES: To evaluate the impact of zidovudine (ZDV) intervention on vertical
      transmission and HIV-related mortality in two groups of pregnant mothers and
      their respective infants. METHODS: A modified long course Paediatric AIDS
      Clinical Trial Group 076 protocol was used. None of the infants was breast-fed.
      Maternal CD4 T lymphocyte counts and viral loads were not monitored. Infants were
      followed for clinical progress, and serial serologic testing was performed to the
      age of 24 months, or until two successive HIV (enzyme-linked immunosorbent assay)
      tests were negative. In a historically case-controlled prospective study, the
      transmission rate in ZDV-untreated mother-infant pairs in which infants were born
      during 1991 through 1995 was compared with the transmission rate in ZDV-treated
      mother-infant pairs in which infants were born between 1996 and 2000. RESULTS: In
      the 151 HIV-seropositive pregnant women and their 153 infants studied (2 pairs of
      twins), 93 mother-infant pairs were treated, and 59 were untreated (control
      group). Vertical transmission occurred in 5.5% [95% confidence interval (95% CI)
      1.9 to 12.5] of the treated group of infants and in 27.1% (95% CI 16.7 to 40.5)
      of the untreated group. There was a 79.7% (95% CI 59.8 to 92.1%) relative
      reduction risk of transmission, which was statistically significant (z =3.18, two
      tailed P= 0.0001). Three infant deaths (3.7%) were recorded in the untreated
      group, and 1(1%) death was recorded in the treated group. In ZDV-untreated
      infants, deaths occurred at age <1 year, resulting from respiratory
      complications. One ZDV-treated infant died at 4 years of age with Pneumocystis
      carinii pneumonia. CONCLUSIONS: Our study demonstrated a statistically
      significant reduction in the vertical transmission of HIV after intervention with
      ZDV therapy.

PMID- 12792383
TI  - Urinary tract infection in very low birth weight preterm infants.
AB  - BACKGROUND: The prevalence of urinary tract infection (UTI) in preterm neonates
      ranges between 4 and 25%. The need for a radiologic investigation has not yet
      been established in very low birth weight premature newborns (<1500 g birth
      weight). PATIENTS AND METHODS: For an 11-year period (1990 to 2001), medical
      records of 62 very low birth weight premature infants admitted to a Level III
      neonatal intensive care unit and who developed UTI were reviewed retrospectively.
      Results of renal ultrasound and voiding cystourethrograms were compared between
      extremely low birth weight infants (birth weight, <1000 g) (Group A, Patient 34)
      and premature infants with birth weight between 1001 and 1500 g (Group B, Patient
      28). RESULTS: UTI was more common in Group A (12.2%) than in Group B (5.7%)
      infants. Renal ultrasound detected mild renal pelvic dilatation (unilateral or
      bilateral) in 9 infants in Group A (26%) and in 1 infant in Group B (3.5%).
      Voiding cystourethrograms were performed in 26 of 34 (76%) infants in Group A and
      in 17 of the 28 (61%) premature infants in Group B. Vesicourethral reflux (VUR)
      was observed in 6 infants, 2 in group A (7.7%) and 4 in Group B (23%).
      CONCLUSIONS: We found that the rate of VUR was lower in very low birth weight
      premature newborns than that reported in the medical literature among term
      newborns who developed UTI. VUR was less frequent in extremely low birth weight
      infants who developed UTI than in infants weighing 1001 to 1500 g.

PMID- 12792384
TI  - Utility of complete blood count and blood culture screening to diagnose neonatal
      sepsis in the asymptomatic at risk newborn.
AB  - BACKGROUND: In May 1996, the CDC recommended obtaining a complete blood count and
      blood culture (BC) from all asymptomatic "at risk" newborns; those > or =35 weeks
      gestation born to mothers with group B streptococcal vaginal colonization or
      those with maternal fever, premature rupture of membranes or previous infant with
      group B streptococcal disease; who did not receive adequate intrapartum
      antibiotic prophylaxis. DESIGN/METHODS: During the study period (May 1996 to July
      1999), a complete blood count and BC were obtained within 4 h from all
      asymptomatic at risk newborns of > or =35 weeks gestation. White blood cell count
      (WBC) and BC results and prevalence of clinical or culture-proven sepsis were
      obtained by chart review. We determined the sensitivity/specificity and
      likelihood ratios of an abnormal WBC (total >30 000 or <5000/mm3; absolute
      neutrophil count <1500/mm3, or a band form-polymorphonuclear cell ratio of >0.2)
      to distinguish between clinically septic vs. nonseptic term at risk newborns.
      RESULTS: Of 20 554 deliveries 1665 were initially asymptomatic at risk newborns;
      17 (1.0%) developed early onset sepsis, all within 48 h. WBC was abnormal in 7 of
      17 (41%) and in 447 of 1648 (27%) who remained nonseptic. None of the 1665 term
      at risk newborns had a positive BC. The sensitivity and specificity of an
      abnormal WBC in predicting which at risk newborns would develop sepsis were 41
      and 73%, respectively. The positive likelihood ratio was 1.52, whereas the
      negative likelihood ratio was 0.81, with an odds ratio of 1.88. CONCLUSIONS:
      Since the implementation of the CDC guidelines for maternal intrapartum
      antibiotic prophylaxis, culture-proved sepsis has become rare at our institution.
      Although BC did not aid in the diagnosis of sepsis among asymptomatic at risk
      newborns, close observation in the first 24 h remained critically important.

PMID- 12792385
TI  - Oral miltefosine treatment in children with mild to moderate Indian visceral
      leishmaniasis.
AB  - BACKGROUND: Miltefosine is the first oral drug with demonstrable success in
      treating visceral leishmaniasis in adults. Because approximately one-half of the
      visceral leishmaniasis patients worldwide are children, we performed a Phase I/II
      dose ranging study in the pediatric population in India. METHODS: Thirty-nine
      (39) children (defined as < 12 years of age) with visceral leishmaniasis
      demonstrated by parasites in splenic aspirates, were treated with oral
      miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and
      18 patients received 2.5 mg/kg/day (Group B). About one-half of these children
      had failed prior antileishmanial treatment. RESULTS: All patients were
      parasitologically negative and symptomatically improved by the end of therapy on
      Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in
      each treatment group relapsed with fever, splenomegaly and parasite-positive
      splenic aspirates by the end of the 6-month follow-up. The per protocol final
      clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B.
      Miltefosine was well-tolerated. As per the adult experience, gastrointestinal
      adverse events were seen: 33 and 39% of children experienced vomiting and 5 and
      17% experienced diarrhea in Groups A and B, respectively, but all episodes were
      mild to moderate in severity and commonly lasted <1 day without symptomatic
      treatment. CONCLUSION: Oral miltefosine was safe and approximately 90% effective
      in this initial clinical trial of childhood visceral leishmaniasis.

PMID- 12792387
TI  - Human papillomavirus vaccines.

PMID- 12792386
TI  - Elevated serum procalcitonin values correlate with renal scarring in children
      with urinary tract infection.
AB  - BACKGROUND: Urinary tract infection (UTI) in young children carries the risk of
      parenchymal damage and sequelae. The location of the infection within the urinary
      tract influences decisions regarding both therapeutics and follow-up. Because
      clinical features and laboratory markers of infection at an early age are not
      specific, it is difficult to make a distinction between lower UTI and acute
      pyelonephritis. Procalcitonin (PCT) has been studied as a marker of severe
      bacterial infection. The aim of this study was to test the usefulness of PCT
      concentration in serum to distinguish between uncomplicated UTI and severe acute
      pyelonephritis with renal scars. METHODS: PCT was measured by immunoluminometric
      assay in serum samples from children with microbiologically documented infection.
      Severe renal involvement was assessed by 99mTc-dimercaptosuccinic acid
      gammagraphy done 5 to 6 months after the episode to check for the presence of
      parenchymal scars. C-reactive protein (CRP) and leukocyte count were also
      measured. RESULTS: PCT at presentation showed a significant correlation (P <
      0.001) with the presence of renal scars in children with UTI. Using a cutoff of 1
      ng/ml for PCT and 20 mg/l for CRP, sensitivity and specificity in distinguishing
      between urinary tract infection with and without renal damage were 92.3 and
      61.9%, respectively, for PCT and 92.3 and 34.4% for CRP. Positive and negative
      predictive values were 32 and 97.5%, respectively, for PCT and 23 and 95%,
      respectively, for CRP. CONCLUSIONS: A low PCT value at admission indicates a low
      risk of long term renal scarring. Increased PCT values at admission correlate
      with the presence of scars. PCT values have proved to be more specific than CRP
      and leukocyte count for identifying patients who might develop renal damage.

PMID- 12792388
TI  - Pediatric ventilator-associated pneumonia.

PMID- 12792389
TI  - Amebic encephalitis caused by Balamuthia mandrillaris: report of four cases.
AB  - We report four fatal cases of amebic encephalitis in children caused by the free
      living pathogenic ameba Balamuthia mandrillaris. The clinical course ranged from
      subacute to fulminant. Provisional diagnoses were made either shortly before
      death or postmortem by an indirect immunofluorescent antibody test. Although the
      four cases occurred in different geographic locations, their common features may
      have diagnostic value for recognizing future cases of amebic encephalitis. The
      cases occurred in children 2 to 7.5 years old who were ostensibly immunocompetent
      and of Hispanic ethnicity. Three of the four children developed hydrocephalus
      during their illness. Increased awareness and timely diagnosis of this disease
      entity might lead to earlier intervention with improved outcome.

PMID- 12792390
TI  - Tuberculous otitis media with mastoiditis and central nervous system involvement.
AB  - Tuberculosis of the middle ear and mastoid is currently a rare disease in
      developed countries, but this disease still occurs and may cause serious
      consequences. We report a case of disseminated tuberculosis involving the middle
      ear, mastoid, lung and central nervous system. Tuberculosis should be considered
      in the differential diagnosis of chronic ear drainage, especially in young
      children.

PMID- 12792391
TI  - Genetic predisposition to infectious pathogens: a review of less familiar
      variants.
AB  - The susceptibility and clinical manifestations of infectious diseases in human
      populations are influenced by a variety of factors, among them host genetics.
      Obvious examples for the effect of host genetics on predisposition to unique
      infections are the primary immunodeficiency diseases. Minor gene variants that
      influence the host immune system are much more common. The iceberg model can be
      used to illustrate the epidemiology of immunodeficiency states. Accordingly only
      a few individuals have known and severe recognized primary immunodeficiencies,
      whereas many more patients have mild immunodeficiencies that may remain
      undiagnosed and are predisposed to a unique infectious disease. We review some of
      the less common variants that influence the host defense and predispose to
      certain infectious agents or change their outcome.

PMID- 12792392
TI  - Organ donation from children with meningitis.

PMID- 12792393
TI  - Procalcitonin, interleukin-6, C-reactive protein and leukocyte counts in infants
      with bronchiolitis.

PMID- 12792395
TI  - Cochlear implants and meningitis: update and recommendations for prevention.

PMID- 12792396
TI  - Applications of MARSSIM.

PMID- 12792394
TI  - Pediatric diagnosis of human immunodeficiency virus type 1 infection: the problem
      of false negative DNA polymerase chain reaction results.

PMID- 12792397
TI  - Interview with Bobby M. Wilson.

PMID- 12792400
TI  - Adapting MARSSIM for FUSRAP site closure.
AB  - The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM)
      provides a coherent, technically defensible process for establishing that exposed
      surfaces satisfy site cleanup requirements. Unfortunately, many sites have
      complications that challenge a direct application of MARSSIM. Example
      complications include Record of Decision (ROD) requirements that are not MARSSIM
      friendly, the potential for subsurface contamination, and incomplete
      characterization information. These types of complications are typically the
      rule, rather than the exception, for sites undergoing radiologically-driven
      remediation and closure. One such site is the Formerly Utilized Sites Remedial
      Action Program (FUSRAP) Linde site in Tonawanda, New York. Cleanup of the site is
      currently underway. The Linde site presented a number of challenges to designing
      and implementing a closure strategy consistent with MARSSIM. This paper discusses
      some of the closure issues confronted by the U.S. Army Corps of Engineers Buffalo
      District at the Linde site and describes how MARSSIM protocols were adapted to
      address these issues.

PMID- 12792399
TI  - MARSSIM vs. DOE Order 5400.5: the Final Status Survey plan at the Rocky Flats
      Environmental Technology Site.
AB  - A challenge unique to the decommissioning of Department of Energy (DOE)
      facilities involves the compromise between the existing and newly recommended
      standards for the unrestricted release of property and materials. The Rocky Flats
      Environmental Technology Site (RFETS) is currently decommissioning numerous
      plutonium contaminated facilities. The default DOE standard for unrestricted
      release, Order 5400.5, defines surface activity guidelines as averaged over a 1
      square-meter area with a maximum value defined for any given 100-square
      centimeter area. While the Order was initially developed to release property and
      materials from an operating site, it is restrictive in its use when performing
      Final Status Survey and, to date, no new complex wide standard has been
      developed. However, the RFETS stakeholders selected the MARSSIM, which provides a
      progressive method to demonstrate compliance with the defined "dose-based" limits
      for a specific site, as the governing document in developing a final survey
      method. The end result is a hybrid final status survey plan that incorporates the
      requirements of both documents. This plan represents several years of development
      and negotiation between the contractor, the DOE, the Colorado Department of
      Public Health and Environment, the Rocky Flats stakeholders, and other interested
      parties.

PMID- 12792398
TI  - Application of MARSSIM at the Big Rock Point Restoration Project.
AB  - Big Rock Point was Michigan's first commercial power reactor and operated for 35
      years. It was permanently shut down in August of 1997, and the site is currently
      being returned to its natural state. Guidance contained in the Multi-Agency
      Radiation Survey and Site Investigation Manual (MARSSIM) is being applied in
      preparation for the final status survey. Unlike other commercial power reactors
      currently undergoing decommissioning, all Big Rock Point structures will be
      removed prior to the final status survey. A historical site assessment along with
      characterization surveys formed the basis to designate 1.6 square kilometers
      (395.9 acres) of the site as non-impacted and the remaining 0.7 square kilometers
      (184.5 acres) as impacted as defined by MARSSIM. Also, a source term abstraction
      has been performed using historical waste stream data to identify radionuclides
      potentially present in site soils, hard-to-detect (HTD) radionuclides and
      surrogate radionuclides for the HTD radionuclides.

PMID- 12792401
TI  - New Jersey and MARSSIM: perfect together (well, almost).
AB  - In order to encourage the timely and efficient cleanup of sites contaminated with
      radioactive materials, the New Jersey Department of Environmental Protection
      revised its Sampling Procedures Manual to follow the MARSSIM (NRC 2000)
      methodology. This was done concurrently with the proposal and subsequent adoption
      of its Soil Remediation Standards for Radioactive Materials (New Jersey
      Administrative Code Title 7, Department of Environmental Protection, Chapter 28
      Radiation Protection Programs, Subchapter 12, Soil Remediation Standards for
      Radioactive Materials).

PMID- 12792402
TI  - MARSSIM recommended in states' guidance document for decommissioning.
AB  - States appreciate guidance for activities done infrequently or at only a few
      locations in the state. For many states, this is the case for decommissioning.
      Some states have reactors being decommissioned, some DOE sites undergoing
      cleanup, and some uranium mill or radium sites. Many, however, only occasionally
      do a small facility cleanup or, once in a great while, a large one. For this
      reason, most states participated in the readily available MARSSIM training and
      now recommend its use. For this same reason, the CRCPD Committee on
      Decontamination and Decommissioning (E24) developed a brief guidance document for
      state and licensee use.

PMID- 12792403
TI  - MARSSIM-based graded approach for posting and controlling areas containing
      matrixed contamination in soil.
AB  - Controlling outdoor areas with radioactive contamination matrixed into the soil
      presents unique challenges to effective radiological control and environmental
      restoration programs. These outdoor areas, classified as either soil
      contamination areas (SCAs) or underground radioactive material areas (URMAs)
      based on the depth distribution of the contamination, constitute a large portion
      of the 1,517 km2 (586 mi2) Hanford Site in south-central Washington state. One of
      the challenges in dealing with these areas is the paucity of regulatory and/or
      interpretive guidance, particularly with 10 CFR 835, "Occupational Radiation
      Protection," which does not address SCAs or URMAs. This leads to differing
      interpretations of applicable regulatory requirements and has caused
      inconsistency among the programs of various Hanford contractors. To overcome
      these shortfalls, the Hanford Site Environmental Restoration Contractor (ERC)
      developed a graded approach for posting and controlling SCAs and URMAs that is
      based on principles of the Multi-Agency Radiation Survey and Site Investigation
      Manual. This approach provides an additional degree of worker protection that
      exceeds the requirements of 10 CFR 835. Each step in this graded approach leads
      to effective environmental restoration of the Hanford Site.

PMID- 12792404
TI  - An approach towards minimization of sample analysis costs for mixed radionuclides
      using MARSSIM for a final status survey.
AB  - Radiological characterization of a site provides extensive information beyond
      that associated with the extent of contamination. A detailed analysis of
      characterization sample results will identify the mix of radionuclides present
      and possible interrelationships between the radionuclides. Once a set of Derived
      Concentration Guidelines Levels are established, it is possible to optimize a
      sample analysis protocol based on the relative importance of each radionuclide to
      the anticipated final dose calculation. In some cases the radionuclides
      identified during characterization will include a complex mixture of easy and
      hard-to-detect radionuclides including alpha emitters. The approach developed in
      this paper considers the percentage contribution of each radionuclide to the dose
      estimate. This discussion is limited to cases where analytical laboratory
      analysis of soil samples has been determined to be the appropriate method to
      demonstrate compliance with the regulatory criteria stated in the form of Derived
      Concentration Guideline Levels.

PMID- 12792405
TI  - A guided tour of COMPASS.
AB  - The COMPASS software was designed to facilitate the use of MARSSIM and guide the
      user into making informed decisions in designing final status radiological
      surveys. COMPASS also simplifies the application of the statistical tests by
      performing the statistical calculations and providing prospective power curves
      that help in determining what level of confidence the user is willing to accept
      for a particular number of measurements or samples for a survey unit. After
      performing the final status survey, COMPASS assesses the data for comparison to
      the release criteria. The purpose of this article is to provide the COMPASS user
      with an overview of the features of the software and to demonstrate how COMPASS
      implements the MARSSIM guidance.

PMID- 12792406
TI  - Technical considerations for using in situ gamma spectroscopy in conducting final
      status surveys.
AB  - Facilities undergoing decommissioning are required to conduct radiological
      surveys to initially characterize contaminants, guide remediation activities, and
      demonstrate that cleanup criteria have been met, based on screening or site
      specific derived concentration guideline levels. This paper presents a number of
      technical considerations, not all inclusive, associated with the use of in situ
      gamma spectroscopy that should be addressed when such a method is proposed for
      conducting final status surveys. The technical issues identified here do not yet
      reflect the policy of the NRC on this subject.

PMID- 12792408
TI  - More focused surveys and a report card update.

PMID- 12792407
TI  - Scan MDCs for multiple radionuclides in Class 1 areas.
AB  - The MultiAgency Radiation Survey and Site Investigation Manual (MARSSIM),
      published in December 1997, has been used for designing final status surveys at a
      number of D&D sites to date. One of the more challenging aspects of the MARSSIM
      survey design is the strategy employed when multiple radionuclides are present,
      particularly in Class 1 survey units. The MARSSIM recommends that potential hot
      spots in a Class 1 survey unit--that could exceed the derived concentration
      guideline levels for small elevated areas of radioactivity (i.e., DCGL(EMC))-
      have a reasonably good probability of being detected. Soil sampling on a
      specified grid size, in conjunction with gamma radiation surface scanning, is
      used to obtain an adequate assurance level that these hot spots are not missed
      during the final status survey. Therefore, it is sometimes necessary to
      supplement the sample size required by the statistical test to provide additional
      assurance that potential hot spots of concern are detected.

PMID- 12792409
TI  - Flavoring meds for children and adults so it goes down easy!
AB  - This article explores the options available to flavor medications, including
      using pantry and refrigerator items, some infant dosing gadgets, pharmacy
      flavorings, and compounded medications. And don't forget, the tips and tricks in
      this article should work for that occasional difficult adult who still thinks and
      acts like a kid!

PMID- 12792410
TI  - Influencing the legislative process: how a bill becomes a law.

PMID- 12792411
TI  - Improving geriatric care knowledge, competency, and resourcefulness of home care
      nurses and aides.
AB  - Home care nurses aides have opportunities to support families caring for frail
      elders; however, most lack specialized geriatric knowledge, competence, and
      resourcefulness skills essential to caring for vulnerable elders and assisting
      their families. This study compares the pretest and posttest intervention scores
      of a geriatric care continuing education program for nurses and aides. Specific
      participant outcomes include increased geriatric knowledge, competency, and
      resourcefulness.

PMID- 12792412
TI  - Key points on caring for pressure ulcers in home care.
AB  - Healthcare providers who care for home-based clients who are at risk for or who
      have a pressure ulcer are confronted with many challenges. Key points specific to
      caring for home care clients are presented to give specific directions so
      clinicians can implement pressure ulcer prevention and care for those who have a
      pressure ulcer.

PMID- 12792413
TI  - 10 ways to lose your Medicare certification.
AB  - This article provides some humorous examples of how agencies might approach their
      Medicare survey and ways to avoid pitfalls in keeping their Medicare
      certification.

PMID- 12792414
TI  - How to improve home care pain management processes.
AB  - This article describes the process and tools one agency used when their ORYX
      indicator, "managing a patient's pain," was consistently below the national
      benchmark. The process can be used for addressing Adverse Events through the OBQI
      Process as well.

PMID- 12792415
TI  - Assessing referral appropriateness in the Intake Department: system changes under
      PPS.
AB  - Since PPS, the Intake Department focus includes evaluation of the level of home
      care services needed and payment coverage criteria. This article focuses on
      questions intake staff should ask to adequately screen for home care eligibility.
      Even though the OASIS assessment cannot be completed prior to the start of care
      visit, screening information can be collected that relate to the OASIS questions.

PMID- 12792417
TI  - Home care.

PMID- 12792416
TI  - Phlebotomy tools of the trade: part 5: protecting yourself from phlebotomy
      related lawsuits.

PMID- 12792420
TI  - Role of the geneticist in testing and counseling for inherited thrombophilia.
AB  - Within the past decade, the identification of two mutations that are relatively
      prevalent among the white population (the factor V Leiden and prothrombin G20210A
      gene mutations) has paved the way for a number of large cohort studies that have
      greatly advanced our understanding of the pathogenesis of venous thromboembolism
      (VTE). VTE is clearly a multigenic disorder, with well-characterized examples of
      gene-gene and gene-environment interactions underlying its pathogenesis.
      Increasing numbers of patients are being referred for testing, and many more
      diagnoses of inherited thrombophilia are being made. The purpose of this article
      is to discuss the practical applications of both diagnostic testing and genetic
      counseling for the major inherited thrombophilias: inherited resistance to
      activated protein C/factor V Leiden, prothrombin G20210A mutation, protein C
      deficiency, protein S deficiency, and antithrombin deficiency. A description of
      each entity is included along with a discussion of the indications for testing,
      selection of the most appropriate screening test, and proper interpretation of
      test results. Informed consent for testing, screening of asymptomatic individuals
      in special circumstances (such as during pregnancy or before initiation of
      estrogen therapy), screening of family members, and posttest education are also
      addressed. This article emphasizes that these polymorphisms should be regarded as
      risk factors for thrombosis whose clinical expression generally depends on the
      coexistence of additional thrombophilic mutations or environmental conditions
      that provoke the development of VTE.

PMID- 12792421
TI  - Comparative evaluation of alpha-galactosidase A infusions for treatment of Fabry
      disease.
AB  - Enzyme therapy has proven safe and effective in preventing and reversing many
      manifestations in patients with Gaucher disease. On the basis of this success,
      enzyme therapy is now becoming a reality for Fabry disease, alpha-galactosidase A
      deficiency. Two products, agalsidase alpha and beta, have been tested in pivotal
      trials. The substantial differences between the study structures and outcome
      measures have made direct comparisons difficult. Here, the strengths and
      weaknesses of these trials are compared: achievement of stated endpoints, safety
      and, potential efficacy. In addition, the need for additional long-term data is
      emphasized because this is not attainable in short-term trials for a chronic
      disease.

PMID- 12792422
TI  - Effects of pregnancy on the renal and pulmonary manifestations in women with
      tuberous sclerosis complex.
AB  - PURPOSE: To determine whether pregnancy increases the risk of renal or pulmonary
      complications in women with tuberous sclerosis complex (TSC). METHODS: We
      surveyed female members of the Tuberous Sclerosis Alliance and reviewed the files
      of adult women seen in our genetics clinics for complications of TSC. RESULTS:
      Among 145 individuals, there was no significant difference in incidence of renal
      and pulmonary involvement between the pregnant and never-pregnant groups,
      although there were differences in age at diagnosis (25 vs. 16) and current age
      (41 vs. 35). There was no significant difference in the rate of renal
      complications (57% vs. 67%, P = 0.62) or pneumothorax (40% vs. 38%, P = 1.00) for
      the pregnant and never-pregnant groups, respectively. Pregnancy loss in women
      with TSC did not differ from population risks. CONCLUSIONS: Pregnancy does not
      increase the risk of developing renal or pulmonary complications in women with
      TSC.

PMID- 12792423
TI  - Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with
      prelingual deafness.
AB  - PURPOSE: To determine the mutation spectrum of the connexin 26 gene among 324
      Taiwanese patients with prelingual deafness and the carrier rate of gene mutation
      in another 432 unrelated control subjects. METHODS: The coding region of the
      connexin 26 gene was sequenced in both directions to detect mutation in all 756
      samples. RESULTS: Among the 756 samples tested, 21 connexin 26 variants were
      detected, including 7 novel ones. The 235delC mutation was the most common,
      accounting for 57.6% of the mutant alleles. Among patients, 48 (14.8%) had
      connexin 26 gene mutations. In the control group, the carrier rate of connexin 26
      mutation was estimated at 2.8%. CONCLUSION: The mutation spectrum of the connexin
      26 gene is wide, with more than half of the patients having only one mutation
      detected. Thus, further efforts are needed to look for possible existence of a
      second mutant allele.

PMID- 12792425
TI  - Predictive genetics in primary care: expectations for the motivational impact of
      genetic testing affects the importance family physicians place on screening for
      familial cancer risk.
AB  - PURPOSE: To investigate whether the importance family physicians place on
      familial cancer-risk screening is influenced by expectations for the motivational
      impact of a high-risk genetic test result. METHODS: Mailed survey of the
      Massachusetts Academy of Family Physicians. RESULTS: Respondents expected
      patients would increase pursuit of screening for cancer (99.6%) and other
      diseases (89.9%), quit smoking (93.6%), and improve diet/exercise (92.5%). The
      degree of motivational effect was significantly related to the importance they
      place on screening. CONCLUSIONS: Family physicians believe that a high-risk
      cancer genetic-test result would motivate their patients to pursue risk-reduction
      behavior, and this belief is related to the importance they place on screening
      their patients for an inherited risk of cancer.

PMID- 12792424
TI  - Physicians' perceived usefulness of and satisfaction with test reports for cystic
      fibrosis (DeltaF508) and factor V Leiden.
AB  - PURPOSE: We sought to determine whether variation in test-report content for
      cystic fibrosis (CF DeltaF508) and factor V Leiden (fVL) would impact physician
      perceived usefulness of and satisfaction with test reports. METHODS: A cross
      sectional survey of US physicians from specialties likely to order the tests was
      performed. Physicians received an introductory letter with a clinical scenario,
      one randomly assigned mock report, and a one-page survey. The analyses evaluated
      usefulness of and satisfaction with report elements. RESULTS: For CF and fVL,
      there were significant differences by mock-report version for most of the survey
      report items (P < 0.05) and for satisfaction (P < 0.0001); results revealed
      greater usefulness and satisfaction with more comprehensive reports. The three
      items in CF and fVL reports where physician-perceived usefulness was most highly
      correlated (R > 0.70) with satisfaction were (1.clinical decision-making
      information, (2). genetic counseling information, and (3). implications for
      family members. CONCLUSION: Opportunities exist to improve the usefulness of
      genetic test reports in clinical practice.

PMID- 12792426
TI  - International genetic testing.

PMID- 12792427
TI  - Update on HIPAA privacy: are you ready?
AB  - The Health Insurance Portability and Accountability Act of 1996 (HIPAA) created
      new requirements for health care providers to protect the privacy and security of
      individually identifiable health information. Regulations to implement HIPAA's
      privacy provisions were published by the Department of Health and Human Services
      (HHS) in "final" form in December 2000 (the Privacy Rules). In March, 2002, HHS
      proposed modifications to the Privacy Rules, which were published on August 14,
      2002. The modified final regulations differed from the 2000 regulations in a
      number of important respects. Most recently, on December 4, 2002, the Office of
      Civil Rights (OCR), which is charged with enforcement of HIPAA, published
      "Guidance Explaining Significant Aspects of the Privacy Rule." The Privacy Rules
      went into effect on April 14, 2003. This article provides a summary of the
      modified Privacy Rules, discusses some interesting aspects of OCR's "guidance,"
      and highlights the requirements that are most likely to impact the practice of
      medical genetics.

PMID- 12792428
TI  - Postmortem findings in the Coffin-Lowry Syndrome.
AB  - The Coffin-Lowry Syndrome (CLS) is a congenital disorder that can be recognized
      by retarded growth and development, the characteristic appearance of the face and
      hands, and often by the typical deformities of the back and chest; there are many
      other anomalies. The history of the syndrome is reviewed, noting the x-linked
      semidominant pattern of inheritance, and two autopsies are presented and compared
      with the three autopsy reports that have been published previously. The five
      young patients died at ages between 18 to 28 years of advancing pneumonia,
      aspiration of food into the trachea, or postoperative complications. There were
      lesions or abnormalities in the heart, brain, lungs, liver, skeleton, kidneys,
      intestines, and other organs. Molecular geneticists have located the CLS gene or
      Rsk-2 gene at Xp22.2 and demonstrated that it works by influencing the activation
      of other genes. The "monopolygenic" pattern may help to explain the large number
      of seemingly unrelated abnormalities that make up this syndrome.

PMID- 12792429
TI  - An argument of logic for the diagnosis of familial hypomobility.

PMID- 12792430
TI  - Practice parameters for ambulatory anorectal surgery.

PMID- 12792431
TI  - Combined seton placement, infliximab infusion, and maintenance immunosuppressives
      improve healing rate in fistulizing anorectal Crohn's disease: a single center
      experience.
AB  - PURPOSE: Infliximab (anti-TNF alpha) has been used for the treatment of
      fistulizing Crohn's disease with variable efficacy. The aim of this study was to
      evaluate the efficacy of infliximab combined with selective seton drainage in the
      healing of fistulizing anorectal Crohn's disease. METHODS: This was a
      retrospective chart review of all patients with fistulizing Crohn's disease
      treated with infliximab between March 2000 and February 2002. RESULTS: Twenty
      nine patients (12 male; mean age, 31 years) received a mean of 3 (range, 1-5)
      doses of infliximab 5 mg/kg. Twenty-one patients had perianal fistulas; eight had
      rectovaginal fistulas, four with combined rectovaginal/perianal fistula. Fourteen
      of 21 patients (67 percent) with perianal fistula had a complete response (mean
      follow-up, 9 months), 4 of the 14 relapsed (mean, 6 months), but all had a
      complete response to retreatment (mean, 9 months). A partial response occurred in
      four patients (19 percent), defined by decreased drainage (2 patients) or
      infliximab dependence (2 patients) requiring repeated dosing every six to eight
      weeks. Three patients (14 percent) had no response. Seton drainage was used
      before infusion in 13 perianal patients for perianal infection and 17 were
      treated with maintenance azathioprine or methotrexate. Of eight patients with
      rectovaginal fistula, complete response occurred in one, partial response in
      five, and no response in two. Two partial responders became infliximab dependent.
      A complete response was observed in one patient with isolated rectovaginal
      fistula, a partial response in five. No patient with a combined
      rectovaginal/perianal fistula had a complete response. Five rectovaginal fistula
      patients were taking maintenance immunosuppressive agents and two had seton
      drainage before infusion. CONCLUSIONS: Selective seton placement combined with
      infliximab infusion and maintenance immunosuppressives resulted in complete
      healing in 67 percent of Crohn's patients with perianal fistula and partial
      healing in 19 percent. Relapse was successfully treated with repeat infusion.
      Concomitant rectovaginal fistula was a poor prognostic indicator for successful
      infliximab therapy.

PMID- 12792432
TI  - Fibrin glue sealing in the treatment of perineal fistulas.
AB  - PURPOSE: The surgical management of complex perineal fistulas, such as high
      transsphincteric and suprasphincteric fistulas, or those associated with Crohn's
      disease, radiotherapy, surgical trauma, or cavity or a secondary tract, is
      associated with the risk of sphincter injury and significant discomfort. Fibrin
      glue may close fistula tracts without muscle division. Therefore, the aim of this
      study was to evaluate the use of fibrin glue sealing in treatment of perineal
      fistulas. METHODS: A retrospective chart review of all patients in whom fibrin
      glue was used for the treatment of perineal fistula was performed. Patients were
      contacted by telephone to establish follow-up. RESULTS: Thirty-seven patients
      underwent injection of fibrin glue for complex perineal fistulas. Twenty-four
      patients had fibrin glue injection as the principal treatment for the perineal
      fistula, and 13 had fibrin glue in conjunction with an endorectal advancement
      flap. The fistula was of cryptoglandular origin in 16 (42 percent) cases and
      associated with Crohn's disease and trauma in 7 (19 percent) and 14 (38 percent)
      patients, respectively. At a mean follow-up of 12.1 months, healing occurred in
      only 15 (41 percent) patients. The healing rate was 33 percent when fibrin glue
      was the principal treatment, and 54 percent when used with an endorectal
      advancement flap. Fistulas of noncryptoglandular origin had a higher success
      rate, although this difference did not reach statistical significance. There was
      no morbidity associated with the injection of fibrin glue. CONCLUSION: In this
      study, fibrin glue had moderate success in the definitive treatment of perineal
      fistulas. However, 33 percent of the patients in whom fibrin glue was the only
      treatment used were able to avoid more extensive surgery. Fibrin glue is
      associated with minimal risk, therefore its application should be considered in
      patients with complex anal fistulas.

PMID- 12792433
TI  - Rectal heat thresholds: a novel test of the sensory afferent pathway.
AB  - PURPOSE: Currently, rectal sensation may be measured by balloon distention or
      mucosal electrostimulation. This study investigated the application of a graded
      heat stimulus to the rectum using a novel thermal probe as a further method of
      evaluating rectal sensory afferent mechanisms. METHODS: A thermal probe specially
      designed in our institution was used to test rectal heat sensitivity in 31
      healthy subjects. This was compared with all other standard anorectal physiologic
      measurements. Repeatability studies were also performed. RESULTS: Heat
      stimulation of the mid rectum elicited sensory responses in all subjects. The
      most common reported response was not heat but a sharp or prickling sensation.
      The median rectal heat threshold was similar in males (median, 47 degrees C;
      range, 44-50 degrees C) compared with females (median, 45 degrees C; range, 43-50
      degrees C; P > 0.05). There was a high degree of repeatability with rectal heat
      and balloon distention thresholds, but not electrostimulation thresholds. A
      strong correlation was found between rectal heat thresholds and defecatory desire
      (r = 0.71; P < 0.001) and maximum tolerable volumes (r = 0.8; P < 0.001) measured
      with balloon distention. CONCLUSION: This is the first demonstration of a
      repeatable sensory response to heat stimulation in the rectum of normal subjects.
      Strong correlation between heat thresholds and balloon distention to maximum
      tolerable volumes and defecatory desire suggest common sensory afferent pathway
      excitation. Heat stimulation is a simple technique that has a high degree of
      repeatability and may be an objective assessment of polymodal nociceptor function
      in the rectum.

PMID- 12792434
TI  - Treatment of hemorrhagic radiation proctitis with 4 percent formalin.
AB  - PURPOSE: The purpose of this study was to review our results in patients
      undergoing treatment with 4 percent formalin for radiation-induced injury to the
      rectum. METHODS: A retrospective review of office charts was performed,
      identifying all patients undergoing formalin treatment. Patient gender, initial
      malignancy, prior treatments, response to treatment with formalin, complications,
      and length of follow-up were reviewed. All patients had flexible endoscopy to
      assess for proximal sources of bleeding. The indication for treatment was a
      symptomatic patient with endoscopic evidence of radiation injury. A cotton
      pledget was used for direct application of 4 percent formalin to the affected
      area via a rigid proctoscope or anoscope. The treatment was repeated if blanching
      did not occur or if bleeding continued. Patients were followed up at three-week
      to four-week intervals and treatment was repeated based on the above indications.
      Treatments were continued until cessation of bleeding occurred or, when treatment
      failed, operative treatment was required. RESULTS: Thirty-six patients were
      identified. Three were lost to follow-up. Symptoms included bleeding in all but
      one patient, who presented with an ulcer. There were 33 (26 male) patients.
      Seventeen (51.5 percent) patients had prior treatment. The number of formalin
      treatments ranged from 1 to 13, with a mean of 3.4. The follow-up ranged from 1
      to 60 months, with a mean of 18 months. Twenty-nine (88 percent) patients had
      improvement or cessation of symptoms. Four (12 percent) patients failed
      treatment. Two patients were noted to have full-thickness ulcers and both failed
      formalin treatment. No complications were noted related to formalin treatment.
      CONCLUSION: We conclude that formalin therapy is a safe and effective form of
      treatment that can be performed in the office with minimal discomfort and no
      complications. It can be performed multiple times until results are achieved.
      Formalin therapy may be useful as a first-line treatment for chronic radiation
      proctitis, however, a prospective controlled trial comparing modalities is
      required to prove this to be true.

PMID- 12792435
TI  - Prospective comparison of laparoscopic vs. open resections for colorectal
      adenocarcinoma over a ten-year period.
AB  - PURPOSE: The aim of this study was to define the long-term oncologic outcomes of
      laparoscopic resections for colorectal cancer. METHODS: We analyzed our
      experience via a prospective, nonrandomized, longitudinal cohort study. The
      period of study extended from April 1991 to May 2001. Laparoscopic resection was
      offered selectively in the absence of a large mass, invasion into abdominal wall
      or adjacent organs, and multiple prior abdominal operations. Every laparoscopic
      resection performed with curative intent for adenocarcinoma was included. Twenty
      percent of patients whose procedures were converted to open resection were
      included in the laparoscopic-resection group because of intention to treat.
      Oncologic outcome measures of this group were compared with a computerized, case
      matched, open-resection group, the case-matching variables being age, gender,
      site of primary tumor (colon vs. rectum), and TNM stage. The laparoscopic
      resection group was followed up prospectively, and data were updated regularly.
      The follow-up techniques consisted of a combination of office visits, telephone
      calls, and the United States Social Security Death Index database. RESULTS: The
      laparoscopic-resection group consisted of 172 patients with a mean age of 67
      (range, 27-85) years. The open-resection group consisted of 172 patients with a
      mean age of 69 (range, 30-90) years. Mean follow-up was 52 (range, 3-128) months.
      Complete (100 percent) follow-up data were available. The TNM stage distribution
      was 63 Stage I (37 percent), 51 Stage II (30 percent), 47 Stage III (27 percent),
      and 11 Stage IV (6 percent) tumors for the laparoscopic-resection group and 65
      Stage I (38 percent), 48 Stage II (28 percent), 51 Stage III (29 percent), and 8
      Stage IV (5 percent) tumors for patients in the open-resection group (P = 0.75,
      not significant). Thirty-day mortality was 1.2 percent (2 deaths) in the
      laparoscopic-resection group and 2.4 percent (4 deaths) in the open-resection
      group (P > 0.05, not significant). Early and late complication incidences were
      comparable. Local recurrence was observed in three patients (1.7 percent) in the
      laparoscopic resection group with the primary tumor in the colon and in three
      patients (1.7 percent) with the primary tumor in the rectum, for a total
      incidence of local recurrence in the laparoscopy group of 3.5 percent (6
      patients). In the open-resection group, local recurrence was observed in two
      patients (1.2 percent) among those with primary tumor site in the colon and in
      three patients (1.7 percent) in the group with primary tumor in the rectum, for a
      total incidence of local recurrence in the open-resection group of 2.9 percent (5
      patients). One of the local recurrences in the laparoscopy group occurred in the
      port/extraction site, for an incidence of 0.6 percent. Metastasis occurred in 18
      patients (10.5 percent) in the open group and in 21 (12.2 percent) in the
      laparoscopy group. Stage-for-stage overall five-year survival rates were similar
      in the two groups. The Kaplan-Meier statistical analysis performed for colonic
      vs. rectal primary adenocarcinoma confirmed that TNM stage for stage-overall
      survival was similar in the laparoscopic and open-resection groups (log-rank P =
      0.22). CONCLUSIONS: Notwithstanding the drawbacks of a nonrandomized study, no
      adverse long-term oncologic outcomes of laparoscopic resections for colorectal
      cancer were observed in a single center's experience during a ten-year period.

PMID- 12792436
TI  - Long-term outcome of perianal Paget's disease.
AB  - PURPOSE: Extramammary Paget's disease of the perianal region is a rare finding
      that often results in delayed diagnosis and treatment. Although the natural
      history of the disease is not well characterized, it historically has been
      associated with other cancers. This study summarizes the history and treatment of
      all patients diagnosed with perianal Paget's disease at a single institution.
      METHODS: Charts of all patients with a diagnosis of extramammary Paget's disease
      of the perianal region confirmed or treated at Memorial Sloan-Kettering Cancer
      Center between 1950 and 2000 were reviewed. Patients with vulvar Paget's disease
      or Bowen's disease were excluded except when Paget's disease of the perianal
      region was diagnosed first. Whenever possible, follow-up information was updated.
      Estimates of overall and disease-free survival were made by the method of Kaplan
      and Meier. RESULTS: Twenty-seven patients with a median age of 63 years were
      diagnosed with perianal Paget's disease. Most patients (74 percent) were treated
      with wide excision. Local recurrence occurred in 37 percent of all patients
      treated and in 30 percent of patients (6/20) undergoing a wide excision as part
      of their treatment. An invasive component was identified in 44 percent of
      patients (12/27) with perianal Paget's disease. Six patients (22 percent)
      required a colostomy as part of the treatment for their disease. Adjuvant
      chemoradiotherapy was used in 22 percent of patients (6/27) who had more
      aggressive disease. At a median follow-up of 67 months, 56 percent (15/27) had no
      evidence of disease, and two patients had died of metastatic disease. The overall
      and disease-free survival at five years was 59 and 64 percent, respectively,
      which decreased to 33 and 39 percent, respectively, by ten years. CONCLUSIONS:
      Perianal Paget's disease is a rare finding even at a large referral center. The
      disease process is generally a prolonged one marked by frequent recurrences, and
      the treatment of first choice is wide excision. Patients with invasive
      malignancies require more extensive surgery. The role of chemoradiotherapy
      remains undefined in this disease.

PMID- 12792437
TI  - Patterns of surgery in patients belonging to amsterdam-positive families.
AB  - INTRODUCTION: The phenotype of hereditary nonpolyposis colorectal cancer includes
      an 80 percent lifetime risk of colorectal cancer, a predominance of lesions
      proximal to the splenic flexure, and a high incidence of synchronous and
      metachronous neoplasia. Although prophylactic colectomy is rarely advised for
      patients with a hereditary nonpolyposis colorectal cancer genotype and a normal
      colon, the presence of advanced neoplasia in the context of a qualifying family
      history or a hereditary nonpolyposis colorectal cancer genotype has led to such
      recommendations. We performed this study to document the patterns of colorectal
      surgery performed for cancer-bearing patients who are part of an Amsterdam
      criteria-positive family and to compare rates of metachronous cancers that follow
      index total or segmental colectomy. METHODS: Family trees fulfilling the classic
      Amsterdam criteria for hereditary nonpolyposis colorectal cancer were identified,
      and all patients for whom surgical and pathology records were available were
      included in the study. Type of surgery and the outcome of subsequent follow-up
      were abstracted. Patients were divided into those treated at the Cleveland Clinic
      and those treated elsewhere. RESULTS: There were 39 families with 93 affected
      patients. These patients had 127 colorectal cancers, 76 (60 percent) of which
      were right sided (proximal to the splenic flexure). Median age at diagnosis of
      the index cancer was 47 (range, 26-81) years. Sixteen patients (17 percent) had
      metachronous cancers and multiple surgeries, whereas four (4 percent) had
      synchronous cancers. Median follow-up for patients who underwent surgery at the
      Cleveland Clinic was 13 (range, 4-49) years, whereas that for those who underwent
      surgery elsewhere was 14 (range, 1-42) years. Sixteen (48 percent) of the 33
      patients who underwent surgery at the Cleveland Clinic had a total colectomy vs.
      7 (12 percent) of the 60 who had surgery elsewhere (Fisher's exact test, P <
      0.001). Only one patient who had surgery at the Cleveland Clinic had a second
      operation for a metachronous cancer (1/17 patients having a segmental resection).
      Fifteen patients who underwent surgery elsewhere needed a second resection for
      metachronous cancer (15/53 patients having a segmental resection; Fisher's exact
      test, P = 0.094). CONCLUSION: We conclude that there is high risk of metachronous
      colorectal cancer if an index cancer in a hereditary nonpolyposis colorectal
      cancer patient (defined according to Amsterdam criteria) is treated by partial
      colectomy. However, this risk can be lowered by performing a total colectomy at
      the time of index surgery, or possibly by effective postoperative surveillance.

PMID- 12792438
TI  - Influence of identification and preservation of pelvic autonomic nerves in rectal
      cancer surgery on bladder dysfunction after total mesorectal excision.
AB  - PURPOSE: Given the improvement in oncologic outcome after the introduction of
      total mesorectal excision for the treatment of rectal cancer, the objective of
      the present study was to determine the frequency of identification and
      preservation of the pelvic autonomic nerves and to identify a possible link
      between postoperative micturition disturbances and the extent of the radical
      resection. METHODS: Between March 1997 and December 2001, 150 patients with
      adenocarcinoma of the rectum (<or=16 cm from the anal verge) underwent surgery,
      with sphincter preservation in 112 cases (74.7 percent). Sixty-three patients (42
      percent) were classified as American Society of Anesthesiologists Stage III and
      two (1.3 percent) as Stage IV. The number of cases with complete identification,
      partial identification, or nonidentification of the autonomic nerves (superior
      hypogastric plexus, hypogastric nerve, and inferior hypogastric plexus) was
      documented and correlated with micturition disturbances (need for a long-term
      urinary catheter). Urine volumes were measured by ultrasound before and after
      surgery. RESULTS: The pelvic autonomic nerves were identified completely in 108
      patients (72 percent), partially in 16 (10.7 percent), and not at all in 26 (17.3
      percent). After the initial phase of the study (n = 50 patients), complete
      identification was realized in 78 percent of cases. Multivariate analysis showed
      that of the predetermined parameters (learning curve for Group I vs. Groups II or
      III, gender, T stage, blood loss, curative surgery, and previous surgery), gender
      (P = 0.006), learning curve (P = 0.019), and depth of penetration of the rectal
      wall (T1/T2 vs. T3/T4; P = 0.028) exerted an independent influence on achievement
      of complete pelvic nerve identification. Sixteen patients (10.7 percent) were
      discharged from the hospital with a urinary catheter. Identification and
      preservation of the pelvic autonomic nerves was associated with low bladder
      dysfunction rates (4.5 vs. 38.5 percent; P < 0.001). In the evaluation of
      preoperative and postoperative bladder function, a urologic history and residual
      urine volume measurements by ultrasound were essential. The information obtained
      from urodynamic studies was of no relevance. CONCLUSIONS: Identification and
      preservation of the pelvic autonomic nerves was achieved in the majority of
      patients and led to the prevention of urinary dysfunction. Gender (P = 0.006),
      learning curve (P = 0.019), and T stage are independent parameters that influence
      outcome.

PMID- 12792439
TI  - Extranodal cancer deposit at the primary tumor site and the number of pulmonary
      lesions are useful prognostic factors after surgery for colorectal lung
      metastases.
AB  - PURPOSE: This study was undertaken to identify prognostic factors that can be
      used to predict prognosis after surgery for lung metastases from colorectal
      carcinoma. METHODS: We reviewed retrospectively the clinical course of 37
      patients who underwent surgical resection of primary colorectal cancer and
      metastatic lung disease at the National Defense Medical College Hospital between
      September 1986 and July 1999. We analyzed the prognostic factors with special
      reference to the clinicopathologic factors of primary tumors. RESULTS:
      Multivariate analysis indicated that the existence of an extranodal cancer
      deposit in the primary lesion (hazard ratio = 4.55, P = 0.009) and three or more
      lung metastases (hazard ratio = 2.9, P = 0.04) were significant indicators for
      poor prognosis. We divided the patients into two groups: Group A (n = 12) had
      neither of these two parameters, and Group B (n = 25) comprised all other
      patients. This two-ranked classification was significantly related to both
      survival rates (3-year and 5-year survival rate, 90.9 and 90.9 percent in Group A
      and 16.1 and 8.1 percent in Group B, respectively; P = 0.0003) and disease-free
      survival after thoracotomy (3-year and 5-year disease-free survival rate, 52.9
      and 39.7 percent in Group A and 5.3 and 5.3 percent in Group B, respectively; P =
      0.002). CONCLUSION: An extranodal cancer deposit at the primary tumor site is a
      new significant prognostic factor after resection of lung metastases from
      colorectal cancer. A two-ranked classification by extranodal cancer deposit and
      the number of pulmonary lesions can provide useful prognostic information for the
      treatment of lung metastasis. Surgical resection of pulmonary metastasis is
      expected to be very useful for patients in Group A.

PMID- 12792440
TI  - Effect of port composition on tumor cell adherence: an in vivo model.
AB  - INTRODUCTION: We have reported previously on an in vitro model to examine tumor
      cell adherence to metal and plastic laparoscopic ports and to port sites through
      which they had been passed. This demonstrated that increased numbers of tumor
      cells were found both on metal ports compared with plastic ports and on the port
      sites through which metal ports had passed. In this study, the in vivo adherence
      of such cells to ports and port sites was investigated. METHODS: LIM 1215 tumor
      cells were injected under direct vision into the pelvises of 16 30-kg female pigs
      (range, 15-70 x 106 cells). A total of 12 ports were inserted through each
      anterior abdominal wall (6 metal and 6 plastic), and these were either left in
      situ for 30 minutes (nondisplaced) or were removed twice and replaced through the
      original wound (displaced). RESULTS: Increasing the tumor cell inoculum resulted
      in increased deposition of tumor cells on both ports (P = 0.002) and on the port
      sites (P = 0.017). Significantly more tumor cells adhered to metal ports than to
      plastic ports (P = 0.04), although this failed to reach significance for the
      sites through which metal ports had been passed (P = 0.066). Although
      displacement of ports did not increase the number of tumor cells that adhered to
      ports (P = 0.45), this did result in more tumor cells being deposited on the port
      sites (P = 0.01). CONCLUSIONS: These data suggest that minimizing the number of
      tumor cells within the abdominal cavity, using plastic ports, and securing ports
      to prevent inadvertent displacement would be expected to reduce the number of
      tumor cells deposited in port sites during operative laparoscopy. This may be
      beneficial in reducing the incidence of port-site metastases after laparoscopic
      surgery for gastrointestinal malignancies.

PMID- 12792441
TI  - Superior mesenteric vein thrombosis after colectomy for inflammatory bowel
      disease: a not uncommon cause of postoperative acute abdominal pain.
AB  - PURPOSE: Thromboembolism is a significant cause of morbidity and mortality in
      inflammatory bowel disease. Several prothrombotic conditions have been
      investigated in inflammatory bowel disease. The aim of this study was to evaluate
      the incidence of symptomatic postoperative superior mesenteric vein thrombosis in
      inflammatory bowel disease patients undergoing colonic resections and to identify
      and characterize their clinical presentation. METHODS: Between January 1999 and
      December 2001, 83 consecutive patients undergoing total colectomy for
      inflammatory bowel disease were studied retrospectively. Patients who developed
      new-onset postoperative acute abdominal pain were evaluated by CT scan of the
      abdomen. A complete coagulation profile, including thrombin time, platelet count,
      protein C, protein S, antithrombin III, homocysteine level, factor V Leiden
      mutation, plasminogen, and prothrombin G20210A mutation, was obtained in patients
      diagnosed with superior mesenteric vein thrombosis. RESULTS: Four patients (4.8
      percent; 3 females; 3 patients with ulcerative colitis and 1 with Crohn's
      colitis) developed symptomatic postoperative superior mesenteric vein thrombosis.
      Two of these patients had extension of the clot into the portal vein. Their
      presenting symptom was abdominal pain, with a median interval of ten days from
      the index surgery. The hematologic workup was negative in three patients, with
      one heterozygous for prothrombin G20210A mutation. All patients were treated with
      systemic anticoagulation for at least six months. One ulcerative colitis patient
      was diagnosed after abdominal colectomy and underwent an uneventful ileal pouch
      anal anastomosis after systemic anticoagulation. CONCLUSION: Postoperative
      superior mesenteric vein thrombosis is a more frequent occurrence than previously
      reported in patients with inflammatory bowel disease. Direct surgical trauma to
      the middle colic veins, with resulting thrombosis, is likely to be the
      precipitating factor in a borderline intrinsically hypercoagulable environment.
      All patients became asymptomatic after systemic anticoagulation and recovered
      uneventfully.

PMID- 12792442
TI  - Outcome analysis in patients with Fournier's gangrene: report of 45 cases.
AB  - INTRODUCTION: Despite antibiotics and aggressive debridement, the mortality rate
      of Fournier's gangrene remains high. Attempts have been made to study factors
      that may affect prognosis; however, reliable criteria are still lacking. METHODS:
      The medical records of 45 patients with Fournier's gangrene who presented at the
      Ege University Medical Faculty Hospital from January 1990 to May 2001 were
      reviewed retrospectively to analyze the outcome and identify the risk factors and
      prognostic indicators of mortality. Univariate analysis was performed using the
      chi-squared test and Fisher's exact probability test, then multivariate analysis
      of statistically significant variables was performed using logistic regression.
      RESULTS: The most prominent associated disease was diabetes, affecting 55.6
      percent of the patients. The overall mortality rate was 20 percent. However, the
      mortality rate among diabetics was 36 percent (P = 0.002). The other
      statistically significant predictors of outcome were the interval from the onset
      of symptoms to the initial surgical intervention (P = 0.001) and the need of
      fecal diversion (P = 0.009). Multivariate regression analysis disclosed that the
      interval from the onset of symptoms to the initial surgical intervention and
      diabetes were independent predictors of mortality (P = 0.001 and P = 0.003,
      respectively). CONCLUSION: The interval from the onset of clinical symptoms to
      the initial surgical intervention seems to be the most important prognostic
      factor with a significant impact on outcome. Given the significantly high
      mortality rate among diabetics, diabetes is also an independent prognostic
      factor. Despite the decreased number of idiopathic cases and extensive
      therapeutic efforts, Fournier's gangrene remains a surgical emergency, and early
      recognition with prompt radical debridement is the mainstays of management.

PMID- 12792443
TI  - Risk factors for anastomotic leakage after left-sided colorectal resection with
      rectal anastomosis.
AB  - PURPOSE: To identify the risk factors for anastomotic leakage after left-sided
      colorectal resections with rectal anastomosis. METHODS: Forty-four patients with
      anastomotic leakage identified from a computer-generated database were compared
      with 44 control patients standardized for gender, age, and operative indication.
      RESULTS: The mean hospital stay was significantly prolonged in the leakage group,
      which resulted in a higher total cost of hospital treatment. The preoperative
      variables significantly associated with anastomotic leakage included
      malnutrition, weight loss, hypoalbuminemia, cardiovascular disease, two or more
      underlying diseases, and use of alcohol. The surgery-related factors that turned
      out to be significant were The American Society of Anesthesiologists physical
      status, operation time greater than two hours, multiple blood transfusions,
      intraoperative contamination of the operative field, and a short distance of the
      anastomosis to the anal verge. Obesity, body mass index, diabetes, smoking, serum
      hemoglobin, serum creatinine, serum bilirubin, bowel preparation, mode of
      antibiotic prophylaxis, type of anastomosis, technique of stapling, size of
      stapler used, and use of drain were nonsignificant variables. Malnutrition,
      weight loss, use of alcohol, intraoperative contamination, long operation time,
      and multiple blood transfusions remained significant in logistic regression
      model. Eighty-six percent of the patients with three or more risk factors of
      anastomotic leakage belonged to the leakage group. CONCLUSIONS: Patients with
      multiple risk factors have higher risk for anastomotic leakage. When patients
      have three or more risk factors, the creation of a protective stoma should be
      considered in cases with a low rectal anastomosis, and all these patients should
      be carefully monitored postoperatively for signs of possible leak.

PMID- 12792444
TI  - Gas volume analysis and postoperative bowel functional disorders in patients who
      received anterior resection for rectal cancer.
AB  - PURPOSE: Colon gas analysis using abdominal radiography has been reported as a
      reliable method for assessing functional bowel disorders. The aim of this study
      was to clarify the relevance of colon gas distribution in postoperative disorders
      such as constipation and feelings of incomplete evacuation following rectal
      cancer operation. METHODS: Colon gas volume score was calculated using plain
      abdominal radiographs and evaluated in 50 patients who had received low anterior
      resections. Twenty-one constipated patients who required laxatives and 29
      patients who did not were compared in terms of colon gas distribution. In
      addition, 32 patients with postoperative feelings of incomplete evacuation and 18
      patients without such feelings were assessed in similar fashion. RESULTS: Left
      colon gas scores in patients who required laxatives were significantly higher
      (2.82 +/- 3.23 percent) than in nonusers (1.21 +/- 0.96 percent; P < 0.01).
      Patients with feelings of incomplete evacuation displayed significantly higher
      left side colon gas scores (2.51 +/- 2.66 percent) than those without such
      feelings (0.77 +/- 0.81 percent; P < 0.0001). CONCLUSION: Patients with
      postoperative functional bowel disorders such as constipation or feelings of
      incomplete evacuation may experience relatively high volumes of gas in the left
      colon.

PMID- 12792445
TI  - Colonic J-pouch-anal anastomosis for rectal cancer.
AB  - PURPOSE: The purpose of this article is to review the different aspects of the
      colonic J-pouch reconstruction with special focus on functional results and
      complications. METHODS: A MEDLINE search from 1965 to the present with manual
      search for older articles was used as the basis of this review. RESULTS: Rectal
      reconstruction using a colonic J-pouch-anal anastomosis after excision of
      extraperitoneal cancers can be performed with acceptable morbidity and good
      functional results. CONCLUSIONS: Among the different methods of rectal
      reconstruction now available after total rectal resection for cancer, the colonic
      J-pouch may be the optimal choice.

PMID- 12792446
TI  - Merkel cell (neuroendocrine) carcinoma of the anal canal: report of a case.
AB  - Merkel cell tumors are rare neuroendocrine tumors typically found on sun-exposed
      areas such as extremities. We describe the case of a 42-year-old female with a
      Merkel cell tumor arising in the anal canal. The tumor was initially thought to
      represent a hemorrhoid arising during pregnancy and was excised locally after
      confirmation of extensive metastatic disease. The patient died 13 months after
      diagnosis with extensive metastatic disease involving the liver. In our search of
      the world literature there are several reports of neuroendocrine tumors in the
      rectum; however, no cases of documented Merkel cell tumors arising in the anal
      canal have been reported. These tumors seem to behave in a very aggressive manner
      when found in other atypical areas. The presentation symptoms were perianal
      discomfort and bleeding. Local excision may be the only surgical treatment
      necessary to control symptoms, given the propensity to early metastases and short
      life expectancy.

PMID- 12792447
TI  - Oral vitamin a therapy for a patient with a severely symptomatic postradiation
      anal ulceration: report of a case.
AB  - Squamous-cell carcinoma of the anus is an uncommon but treatable gastrointestinal
      malignancy. Radiation, in addition to chemotherapy, is widely accepted as the
      standard of care for treatment in most patients. However, significant anal
      complications, such as stricture, fistula, and ulceration, may result from
      radiation therapy. Some medical therapies have been used for radiation
      proctopathy, but treatments for radiation-induced anal injury other than surgical
      diversion are unknown. Vitamin A has been shown in laboratory studies to
      facilitate wound healing and prevent radiation-induced gastrointestinal damage.
      However, it has not been used clinically in patients with radiation enteritis,
      proctopathy, or anal ulceration. We report a case of a patient with human
      immunodeficiency virus infection who developed a symptomatic anal ulcer after
      receiving high-dose radiotherapy for anal squamous-cell carcinoma. We prescribed
      8,000 IU of oral vitamin A twice daily and within seven weeks his anorectal
      symptoms and anal ulcer completely resolved. Vitamin A seems to be very effective
      in the treatment of radiation-induced anorectal damage, with little toxicity and
      expense.

PMID- 12792448
TI  - A different type of presacral tumor: extramedullary hematopoiesis: report of a
      case.

PMID- 12792449
TI  - A most memorable patient.

PMID- 12792450
TI  - Muscle tamponade to control presacral venous bleeding.

PMID- 12792451
TI  - Parameters of rectoanal inhibition in anorectal disease.

PMID- 12792452
TI  - ECT in The Lancet: praising faintly but fairly.

PMID- 12792453
TI  - Decisional capacity of severely depressed patients requiring electroconvulsive
      therapy.
AB  - OBJECTIVE: The decisional capacity of severely depressed people frequently comes
      into question. The ability to improve this decisional capacity through
      educational efforts alone is not known. Our study aimed to determine the
      decisional capacity of severely depressed people requiring electroconvulsive
      therapy (ECT), and whether educational interventions improve their ability to
      provide informed consent for ECT. MATERIALS AND METHODS: Forty subjects with
      severe depression were recruited. Using the MacArthur Competence Assessment Tool
      for Treatment instrument, decisional capacity was assessed at baseline and
      reassessed after education. All of the subjects received standard education.
      Additionally, half were blindly randomized to receive an experimental educational
      intervention. RESULT: SAt baseline, there was no statistical difference in the
      decisional capacity between the standard and experimental intervention groups.
      After educational interventions, all four areas of decisional capacity improved
      for both groups (understanding p < 0.001, reasoning p < 0.001, appreciation p =
      0.031, choice p = 0.006). However, there was no measurable additional improvement
      in scores for those randomized to receive additional education. CONCLUSION: Our
      findings indicate that this group of severely depressed people had good
      decisional capacities to give informed consent. Education improved their
      decisional capacity. There is an endpoint beyond which additional educational
      intervention does not result in measurable improvement in decisional capacity.

PMID- 12792454
TI  - Short-term effect of ECT in middle-aged and elderly patients with intractable
      catatonic schizophrenia.
AB  - BACKGROUND AND OBJECTIVE: The management of middle-aged and elderly patients with
      catatonic schizophrenia has long been a major problem in clinical geriatric
      psychiatry. Most cases are intractable because of medication resistance,
      medication intolerance, or severe medical conditions. Electroconvulsive therapy
      (ECT) is recognized as one of the most efficacious therapies for catatonic
      schizophrenia. Thus, we conducted a prospective study of the short-term effect of
      acute ECT on middle-aged and elderly patients with intractable catatonic
      schizophrenia. MATERIALS AND METHODS: Subjects were nine consecutive patients
      older than 45 years who had fulfilled the DSM-IV criteria for catatonic-type
      schizophrenia and had been referred for first-time acute ECT after other
      treatments had failed. The patients were treated at Tohoku University Hospital
      between January 1998 and March 2002. We evaluated the clinical response of these
      patients to acute ECT by means of the brief psychiatric rating scale (BPRS). We
      also evaluated adverse effects of acute ECT. RESULTS: The response rate was 100%.
      The total BPRS score was improved in all nine subjects at the end of the ECT
      course and 1 week after the final session in comparison with the total pre-ECT
      BPRS score (11.9 +/- 7.5 and 9.3 +/- 9.2 versus 57.1 +/- 13.1, respectively, p =
      0.008, p = 0.008). The total Global Assessment of Functioning score was also
      improved significantly (from 10.8 +/- 9.4 just before ECT to 61.6 +/- 18.9 1 week
      after ECT, p = 0.008). Guy's five factors (thought disturbance, activation,
      anxiety-depression, hostility-suspiciousness, and anergia) improved significantly
      (p = 0.008, p = 0.008, p = 0.018, p = 0.012, p = 0.008, respectively). One
      patient showed supraventricular premature contractions (SVPCs) during an ECT
      seizure. After some ECT sessions, three patients exhibited mild to moderate
      delirium that disappeared within 3 days. However, no patient experienced a severe
      cognitive or physical adverse effect during the course of ECT. CONCLUSIONS: Acute
      ECT has a good short-term effect on middle-aged and elderly patients with
      intractable catatonic schizophrenia and appears to be safe. Our results indicate
      that systematic studies on a large scale are warranted for further investigation
      of the efficacy and safety of acute ECT for treating middle-aged and elderly
      patients with catatonic schizophrenia.

PMID- 12792455
TI  - Confirmation of whole-brain kindling with repeated subthreshold electroconvulsive
      shocks: a controlled study.
AB  - BACKGROUND: Repeated, subconvulsive electroconvulsive shock (ECS) stimuli,
      administered a day apart, lower the ECS seizure threshold in rats. It is not
      known, however, whether this kindling results from the repeated subconvulsive
      stimulation or from the stress induced by the experimental procedures. MATERIALS
      AND METHODS: Adult, male Wistar rats were randomized to receive a 3-mC ECS
      stimulus (n = 20), a 30-V (0.3-s) footpad shock (n = 20), or sham ECS and sham
      footpad shock (n = 20). All procedures were conducted once daily for 3
      consecutive days. On the fourth day, all rats received a 3-mC ECS stimulus.
      RESULTS: At the end of the experiment, 85% of the rats in the ECS group but only
      35% of the rats in each of the other two groups had experienced a seizure with
      the 3-mC stimulus (p < 0.001). CONCLUSION: The lowering of the ECS seizure
      threshold by repeated, once-daily subconvulsive stimuli is caused by the
      subconvulsive stimulation itself, not by experimental stress.

PMID- 12792456
TI  - Has the practice and outcome of ECT in adolescents changed? findings from a whole
      population study.
AB  - OBJECTIVE: To investigate whether there were changes in the practice and outcome
      of electroconvulsive therapy (ECT) in adolescents in a whole population over a
      decade. METHOD: All persons younger than 19 years who received ECT in the state
      of New South Wales, Australia, in the period from 1990 to 1999 were identified.
      Detailed information about diagnosis, treatment and outcome were then obtained.
      RESULTS: Seventy-two patients aged 14-18 years underwent a total of 84 courses of
      ECT (1.53/100,000 adolescents were treated with ECT per year). In 1996 to 1999
      compared with 1990 to 1995, there was an increase in ECT among females
      hospitalized involuntarily, EEG monitoring, stimulus dosing, bilateral ECT, and
      use of thiopentone. Overall, mood disorders derived most benefit from ECT while
      comorbid personality disorder predicted poorer short term outcome. Side effects
      were minor and transient. CONCLUSIONS: The changes in ECT practice are consistent
      with changes in ECT practice generally over the survey period. The overall data
      on effectiveness and safety further support the treatment's use in young people.

PMID- 12792457
TI  - How fixed are child psychiatrists' views about ECT in the young?
AB  - The experience, knowledge, and attitudes of Australian and New Zealand child
      psychiatrists in relation to ECT in the young were surveyed in 2000 to ascertain
      whether their views had changed since a similar survey was conducted in 1996.
      Fifty-four percent (n = 129) of the original sample answered a mailed
      questionnaire. Psychiatrists in 2000 had greater self-rated level of knowledge on
      the subject and were less likely to base that knowledge on adult ECT data.
      Psychiatrists in 2000 were also more likely than in 1996 to approve the use of
      ECT in adolescents. The finding that the views of child psychiatrists can change
      is reassuring, given emerging data showing ECT in young persons to be an
      effective and safe treatment, and the requirement in various countries that child
      psychiatrists participate in the decision to administer the treatment. It is
      possible that a number of publications and presentations on the topic after the
      first survey contributed to the change in views. Nevertheless, there remain gaps
      in child psychiatrists' knowledge about ECT in the young that need to be
      addressed. The study findings should not be over interpreted because of the
      reduced response rate in the follow-up survey.

PMID- 12792458
TI  - ECT in the Asia Pacific region: what do we know?
AB  - OBJECTIVE: To review and describe the practice of ECT in the Asia Pacific region
      in the year 2000. METHOD: A survey of 34 defined countries within the Asia
      Pacific region was made prior to the 1st Asia Pacific ECT Conference held in
      Melbourne, Australia, 2001. RESULTS: Contact addresses for 23 of 34 countries
      (70%) were found with responses from 12 different countries (35%). Individual
      responses were received from less than 1% of the total mail out for the
      conference. The percentage of inpatients who received ECT was consistently less
      than or equal to 9%, except for Nepal where it was 25.6%. Except for Kiribati and
      the Solomon Islands, all devices delivered brief pulse, square wave currents. All
      of the 12 countries surveyed used anesthesia, preferred bilateral electrode
      placement and reported a response rate of at least 86%. Adverse events were
      uncommon, memory being the most commonly reported side effect. Community
      attitudes were generally negative. CONCLUSION: Despite the difficulties in
      attempting to generalize about this huge and diverse region, a number of
      seemingly universal findings appeared in accord with the world literature. These
      included the widespread use of ECT, its effectiveness and its relative safety
      despite equally widespread community reluctance.

PMID- 12792459
TI  - Electroconvulsive therapy in Hong Kong: rates of use, indications, and outcome.
AB  - INTRODUCTION: There has been a concern about indiscriminate use of
      electroconvulsive therapy (ECT) in Asian countries. This study examined the rates
      of ECT use and the characteristics and outcomes of patients treated with ECT in
      Hong Kong. METHOD: A central database of ECT treatments was used to calculate
      annual rates of ECT use from 1997 to 2002. We surveyed prospectively patients
      received ECT over 12 months by a standardized questionnaire. RESULTS: The ECT
      utilization rates varied from 0.27 to 0.34 patients treated per 10,000 population
      and 1.34 to 1.88 patients treated per 100 inpatients discharged. There were
      differences in the pattern of ECT use among Hong Kong, the United States, and the
      United Kingdom. Only 15% of ECT recipients were 65 years old or older and 23% had
      schizophrenia as primary diagnosis for ECT. Ninety-five percent of patients who
      received ECT improved with the treatment as assessed by clinicians. No severe
      complications and deaths occurred, and 6% stopped ECT due to undesirable results.
      CONCLUSION: The rate of ECT use in Hong Kong continues to be below that in the
      United States and the United Kingdom. Access to ECT is most limited to the
      elderly and private patients.

PMID- 12792461
TI  - Diminished ECT response in catatonia due to chronic neurologic condition.
AB  - A series of four clinical cases suggests that catatonic disorder due to a chronic
      neurologic condition does not respond as reliably to electroconvulsive therapy
      (ECT) as functional catatonia does. Cases reported in the medical literature show
      a similar pattern. Presumably this form of catatonia is intrinsically less
      responsive to ECT, although the possibility remains that a more intense quality
      of treatment and prophylaxis is needed. Conversely, catatonia resistant to ECT
      suggests an underlying medical condition.

PMID- 12792460
TI  - Electroconvulsive therapy for patients with major depression and probable Lewy
      body dementia.
AB  - Patients with dementia and depression are commonly encountered in ECT practice. A
      large body of case reports and case series in demented patients attests to the
      utility of ECT in treating concomitant depression in this population. However,
      there are no reported cases of patients with suspected Lewy Body dementia and
      depression treated with ECT. We describe our experience in treating seven such
      patients. All of them enjoyed substantial relief from depression with ECT, which
      they tolerated well. It is concluded that ECT can be effective in treating
      depression associated with probable Lewy Body dementia.

PMID- 12792462
TI  - Gilles de la Tourette form of catatonia: response to ECT.

PMID- 12792463
TI  - Administration of ECT in a patient with an inoperable abdominal aortic aneurysm:
      serial imaging of the aorta during maintenance.
AB  - This case report reviews the treatment of a 74-year-old man with an abdominal
      aortic aneurysm, bipolar affective disorder, and Lewy body dementia who
      demonstrated a remarkable positive response to an acute and maintenance course of
      electroconvulsive therapy (ECT) treatment. This is the first report with serial
      imaging of an abdominal aortic aneurysm during maintenance ECT. There are limited
      alternative therapies for those patients who do not meet surgical criteria for an
      abdominal aortic repair because of dementing disorders. In patients who suffer
      comorbid mood disorders, ECT has been shown to be an effective option in
      preserving quality of life and successfully stabilizing the level of agitation.

PMID- 12792464
TI  - Does absolute charge administered predict speed of response to right unilateral
      ECT?

PMID- 12792465
TI  - Need for homogeneity of diagnosis in studies on the cognitive effects of ECT.

PMID- 12792466
TI  - Low dose, lack of power not a test of sevoflurane burst suppression therapy.

PMID- 12792467
TI  - One-minute schirmer test with anesthesia.
AB  - PURPOSE: The 5-minute Schirmer test is a commonly described test for dry eye
      syndrome but is impractical for most ophthalmologists to perform routinely
      because of the 5-minute time frame. Hence, we decided to evaluate the
      intraindividual reliability of different wetting times of the Schirmer basal tear
      secretion test correlated to that of the standard 5-minute Schirmer test.
      METHODS: A prospective study was performed using 60 eyes of 30 patients. All
      patients had symptoms of dry eye syndrome. Patients were excluded if they had
      anatomic lid abnormalities that could interfere with the conduct of the test. The
      reliability of the Schirmer test at 30 seconds and 1, 2, 3, and 4 minutes was
      compared with that of the standard 5-minute test using the intraclass correlation
      coefficient (ICC). RESULTS: The ICC for each eye was only moderate at 30 seconds
      but was high to extremely high thereafter. Specifically, at 1 minute, the ICC for
      right eyes was 0.938 and for left eyes was 0.817. Furthermore, 100% of patients
      with severe dry eye (defined as a 5-minute Schirmer test of 5.5 mm or less) had a
      1-minute Schirmer test less than or equal to 2 mm. Also, 80% of patients with a
      moderate dry eye (defined as a 5-minute Schirmer test between 5.5 to 10 mm) had a
      1-minute test between 3 to 6 mm. CONCLUSION: Our results support the hypothesis
      that shorter durations of the 5-minute Schirmer test correlate highly with those
      of the 5-minute test. Specifically, the 1-minute test correlates highly with the
      5-minute test and will make this test much more practical for ophthalmologists.

PMID- 12792468
TI  - Repair of scleromalacia using preserved scleral graft with amniotic membrane
      transplantation.
AB  - PURPOSE: To evaluate the use of preserved scleral graft with amniotic membrane
      transplantation (AMT) for the surgical repair of scleromalacia. METHODS: A
      prospective study of eight eyes (eight patients) was performed. We grafted
      glycerin-preserved sclera onto the areas of scleral thinning with impending
      perforation and then covered them with an amniotic membrane with a thick basement
      membrane instead of a conjunctival flap. RESULTS: All patients experienced loss
      of ocular pain and inflammation, rapid reepithelialization of the ocular surface,
      and marked improvement in visual acuity. All of the scleral grafts remained
      intact, and no recurrence of scleromalacia was observed. CONCLUSION: Preserved
      scleral graft with AMT was simple, fast, and effective. It was particularly
      advantageous when large scleral defects or conjunctival scarring was present.
      With these therapeutic results, preserved scleral graft with AMT qualifies as a
      new treatment alternative for scleromalacia.

PMID- 12792469
TI  - Confocal microscopy of Thygeson's superficial punctate keratopathy.
AB  - PURPOSE: To describe the changes seen with the confocal microscope in Thygeson's
      superficial punctate keratopathy (TSPK). METHODS: Confocal microscopy was
      performed on six patients with TSPK presenting to Manchester Royal Eye Hospital
      from October 1999 to June 2001. Both eyes were examined including the normal
      fellow eyes of two patients with unilateral TSPK. Images were compared with age
      matched controls. RESULTS: Irregular nerve fibers, masked by considerable haze,
      were seen in the subepithelial nerve plexus immediately above Bowman's membrane
      in TSPK. Generalized haze was also present in the anterior stroma along with
      areas of high reflectivity, microdots, and reflective bodies. Keratocytes had
      highly reflective nuclei and cell bodies of irregular size, orientation, and
      shape. The changes were related to the duration of TSPK, were not seen in normal
      fellow eyes, and were also present in areas without lesions. CONCLUSION: Confocal
      imaging of TSPK demonstrated considerable abnormalities in the subepithelial
      nerve plexus, Bowman's membrane, and the anterior stroma that were related to
      disease duration. Similar changes have been reported in a variety of corneal
      diseases and following laser corneal surgery. Recent evidence has supported
      interactions between the epithelium and Bowman's membrane and the anterior stroma
      in corneal disease and after laser corneal surgery. We speculate that such
      interactions may have a role in TSPK.

PMID- 12792470
TI  - Advanced fusarium keratitis progressing to endophthalmitis.
AB  - PURPOSE: To review the clinical course, treatment, and visual outcomes of
      keratitis with endophthalmitis caused by the filamentary fungus Fusarium. METHOD:
      One hundred fifty-nine cases of Fusarium keratitis at Bascom Palmer Eye Institute
      between January 1, 1987 and August 21, 2000 were reviewed. Ten patients with
      culture-proven Fusarium keratitis progressed to endophthalmitis. All 10 underwent
      standard diagnostic microbiologic evaluation, and topical and oral antifungal
      therapy was instituted. Surgical therapy was applied when necessary. Main outcome
      measures included the incidence of intraocular invasion of fungal keratitis and
      response to treatment. RESULTS: Ten cases of 159 Fusarium keratitis patients had
      intraocular involvement that was culture proven. The isolated species were
      Fusarium oxysporum in seven cases and Fusarium solani in two cases, and in one
      case, the species could not be identified. Cultures of aqueous and intraocular
      tissues grew Fusarium in eight cases, whereas vitreous cultures were positive in
      two. Nine cases had preexisting risk factors. All patients received oral
      ketoconazole or fluconazole and topical natamycin 5%. In two cases, intravitreal
      amphotericin B injections were also given. Four patients required a penetrating
      keratoplasty, enucleation was performed in two patients, two patients required a
      combination of a penetrating keratoplasty and pars plana vitrectomy, and one
      patient developed phthisis. CONCLUSION: The combination therapy with oral
      imidazoles (fluconazole or ketoconazole) and topical natamycin is inadequate in
      severe Fusarium keratitis with intraocular spread. Early diagnosis and suspicion
      of endophthalmitis in patients with keratomycosis not responding to aggressive
      topical antifungal are important.

PMID- 12792471
TI  - Corneal epithelial thinning profile induced by long-term wear of hydrogel lenses.
AB  - PURPOSE: To characterize the epithelial thickness profile and study the effects
      of long-term wear of hydrogel lenses on this profile. METHODS: A cross-sectional
      study was designed. Epithelial thickness was evaluated in 15 subjects who had
      worn one of two types of low oxygen transmissibility (Dk) hydrogel contact lenses
      for an average of 10 years (range, 7-16) and compared with a group of 18 control
      subjects who had never worn contact lenses. Epithelial thickness was measured at
      the center and at four mid-peripheral and four peripheral locations in the
      vertical and horizontal meridians of the cornea using a modified optical
      pachymeter. RESULTS: Lens wearers had significantly thinner epithelium than
      controls [analysis of variance (ANOVA), p < 0.001] in the central (41 +/- 7
      microm versus 48 +/- 5 microm), mid-peripheral (41 +/- 7 microm versus 48 +/- 7
      microm), and peripheral (42 +/- 9 microm versus 48 +/- 6 microm) cornea. The
      extent of this difference ranged from 8.7% to 18.4% of the total epithelial
      thickness, was not associated with the duration of wear (ANOVA, p = 0.87, power =
      0.05), and was significantly greater for the lower Dk contact lens type (ANOVA, p
      < 0.001). Topographical position did not have a significant effect on epithelial
      thickness (ANOVA, p > 0.13, power > 0.22). CONCLUSION: This study establishes
      that the epithelial thinning associated with hydrogel lens wear is
      topographically uniform. It also confirms that this effect is inversely related
      to lens oxygen transmissibility but does not appear to increase with longer
      duration of wear.

PMID- 12792473
TI  - Corneal topography and accommodation.
AB  - PURPOSE: To investigate whether there are significant changes in corneal
      topography during accommodation in normal corneas and corneas that are
      pathologically thinner due to keratoconus. METHODS: A videokeratoscope was
      modified to present an accommodation stimulus that was coaxial with the
      instrument's measurement axis. Six subjects with normal corneas and four subjects
      with keratoconus were studied. Eighteen videokeratoscope measurements of one eye
      of each subject were taken at 0 diopter (D) accommodation demand and six for both
      of 4 D and 9 D accommodation demand. The effects of ocular micromovements on
      multiple topography maps were minimized using software algorithms. Average maps
      for the 4 D and 9 D accommodation demands were calculated and subtracted from the
      average map of the 0-D accommodation demand. A t test was applied at each point
      location within the topography maps to analyze the statistical significance of
      change (p < 0.001) within the difference maps. RESULTS: In the initial analysis,
      we found that a number of the subjects showed significant changes in corneal
      topography as accommodation changed. However, further analysis showed a
      significant group mean excyclotorsion of the topography maps of 1.6 +/- 1.1
      degrees (p < 0.03) for the 4-D stimulus and 2.0 +/- 1.3 degrees (p < 0.01) for
      the 9-D stimulus compared with the 0-D stimulus. When we accounted for the
      excyclotorsion, we did not find clear evidence of statistically significant
      changes in corneal topography as a result of accommodation, either for the normal
      corneas or the keratoconic corneas. CONCLUSIONS: It appears unlikely that changes
      occur in central corneal shape during accommodation up to a level of 9 D in
      normal or keratoconic corneas. A small ocular excyclotorsion typically
      accompanies accommodation, and this changes the relative orientation of the
      topography of the cornea. This has significant implications for the
      interpretation of the optical characteristics of eyes during near viewing
      conditions.

PMID- 12792472
TI  - Scleral contact lenses may help where other modalities fail.
AB  - PURPOSE: To describe the vision-correcting and therapeutic benefits of gas
      permeable scleral contact lenses (GP-ScCL) in the management of irregular corneal
      surface disorders and ocular surface diseases. METHODS: The charts of 48
      consecutive patients (66 eyes) whose management included the use of GP-ScCL were
      reviewed. RESULTS: The most common indication for fitting the lenses was
      keratoconus in patients who had to stop wearing other types of corneal lenses (44
      eyes, 74.6%). Other indications included extreme corneal irregularity after
      penetrating keratoplasty, nonhealing corneal ulcer, postoperative dry eye
      syndrome following laser in situ keratomileusis (LASIK), severe exposure
      keratitis and acid burn. Mean follow-up was 17 months (range, 2-96). Mean wearing
      time of the GP-ScCL was 16.2 hours per day (range, 3-18). Visual acuity of 20/40
      or better was achieved in 90.9% of keratoconus patients and in 81.8% of
      postkeratoplasty patients. A gain of two or more Snellen lines was observed in
      94.5% of eyes treated for improving vision. Marked subjective improvement in
      quality of life was reported by 86% of the patients, mainly as a result of
      improvement in their visual function and reduction in discomfort. Five patients
      (seven eyes) failed to wear GP-ScCL. CONCLUSION: GP-ScCL can provide successful
      and safe visual and therapeutic solutions for ocular conditions when conventional
      contact lenses and medical treatment have failed and where surgery is undesirable
      or contraindicated.

PMID- 12792474
TI  - Long-term progression of astigmatism after penetrating keratoplasty for
      keratoconus: evidence of late recurrence.
AB  - PURPOSE: To study changes in astigmatism throughout a 20-year period using
      keratometry and refraction in patients who underwent penetrating keratoplasty
      (PKP) for keratoconus. METHODS: We reviewed the charts of patients who underwent
      PKP for keratoconus from 1975 to 1979 and recorded preoperative refraction, stage
      of keratoconus, laterality of surgery, graft size, suture technique, time of
      suture removal, keratometry, subjective refraction at 1, 3, 5, 7, 10, 15, 20, and
      25 years after suture removal, and slit-lamp findings. RESULTS: Eighty eyes with
      a mean follow-up of 20 years (range, 15-25) were included in the study. Graft
      size, suture technique, and time of suture removal had no significant influence
      on the astigmatism at the last examination. We observed a stabilization of
      keratometric astigmatism in the first 7 years (4.05 +/- 2.29 D 1 year after
      suture removal, 3.90 +/- 2.28 D at year 3, 4.03 +/- 2.49 D at year 5, 4.39 +/-
      2.48 D at year 7) followed by a progressive increase from 10 years after suture
      removal until the last follow-up visit (5.48 +/- 3.11 D at year 10, 6.43 +/- 4.11
      D at year 15; 7.28 +/- 4.21 D at year 20, and 7.25 +/- 4.27 D at year 25). The
      mean absolute value of the difference vector (DV) calculated by vector analysis
      was 7.17 +/- 4.35 D (0-18.33). In 70% of cases, progression of the astigmatism
      was evident with mean absolute DV of 9.10 +/- 3.65 D. There was a significant
      correlation between the preoperative and final axis of astigmatism (Pearson r =
      0.39, p = 0.0008). There was also a slight positive correlation coefficient
      between the DV of the eyes in bilateral cases, but it was not significant
      (Spearman's r = 0.2226, p = 0.34). The major late slit-lamp finding was a
      peripheral crescent-shaped thinning at the graft-host junction with absence of
      Bowman's layer on histopathology. CONCLUSION: In spite of refractive stability
      obtained during the first years after PKP for keratoconus, increasing astigmatism
      thereafter suggests that there is a progression of the disease in the host
      cornea.

PMID- 12792475
TI  - Comparison of implantable contact lens and laser assisted in situ keratomileusis
      for moderate to high myopia.
AB  - PURPOSE: To compare the results of laser assisted in situ keratomileusis (LASIK)
      and implantable contact lenses (ICL) in the correction of moderate/high myopia.
      METHODS: Five hundred fifty-nine LASIK eyes from the Davis Duehr Eye Center,
      Madison, WI, and 210 ICL eyes from the 14-site U.S. FDA Clinical Trial for ICL
      for Myopia were compared. These series were concurrently operated on with 8 to 12
      D of preoperative myopia and were examined at 1 day, 1 week, 1 month, 6 months,
      and 1 year postoperatively. The mean baseline myopia was slightly higher in the
      ICL group, (ICL: -9.8 +/- 1.7 D; LASIK: -9.1 +/- 0.97 D). BSCVA, UCVA, and
      refractions were collected prospectively in both series. RESULTS: Every index of
      BSCVA, UCVA, predictability of refraction, and stability of refraction studied
      favored the ICL over the LASIK procedure. All but one of the indices (UCVA %
      20/40 or better) were statistically significant in at least half of the time
      periods studied. At 6-month follow-up, both the loss of two or more lines (ICL:
      0%; LASIK: 2%; p = 0.05) and gain of two or more lines (ICL: 7%; LASIK: 3%; p =
      0.04) of BSCVA were better with the ICL. Similarly, efficacy outcomes with the
      ICL were better with predictability (attempted versus achieved +/-1.0 D) of the
      ICL at 90%; 76% with LASIK (p < 0.001). In this highly myopic series, UCVA 20/20
      or better was 50% with ICL compared with 35% with LASIK (p < 0.001). No serious
      complications occurred in either series of cases. CONCLUSIONS: The ICL was safer
      and more effective than LASIK and appears to be a viable alternative to corneal
      refractive excimer surgery in the treatment of moderate to high myopia.

PMID- 12792476
TI  - Modulation of IL-8 and RANTES release in human conjunctival epithelial cells:
      primary cells and cell line compared and contrasted.
AB  - PURPOSE: Recent research indicates that epithelial cells of the ocular surface
      can contribute to the allergic reaction by the release of inflammatory and/or
      chemotactic mediators. In this study, the role of two inflammatory mediators,
      previously identified in the tear film of ocular allergy subjects, TNF-alpha and
      IFN-gamma, were evaluated for their effect on the release of two chemotactic
      mediators, IL-8 and RANTES, from cultured human conjunctival epithelial cells.
      METHODS: Human conjunctival epithelial cells (primary cells or HC0597 cell line)
      were grown to confluence and stimulated with various concentrations of TNF-alpha,
      IFN-gamma, or a combination of both. Supernatants were collected at 6, 24, and 48
      hours and stored frozen for subsequent ELISA analyses of RANTES and IL-8.
      RESULTS: RANTES and IL-8 release from HC0597 cells was stimulated in a dose- and
      time-dependent manner following treatment with TNF-alpha. However, only RANTES
      release was modulated by IFN-gamma treatment. Treatment of HC0597 cells with both
      TNF-alpha and IFN-gamma resulted in a synergistic increase in the release of
      RANTES. This synergistic effect was confirmed using primary cultures of human
      conjunctival epithelial cells. CONCLUSIONS: Stimulation of conjunctival
      epithelium with proinflammatory mediators, TNF-alpha and/or IFN-gamma, generated
      the release of the chemotactic factors IL-8 and RANTES, which could act to
      prolong inflammation. These two chemokines may prolong inflammation by recruiting
      eosinophils to the ocular surface. This is the first study to compare chemokine
      release in a cell line and primary cells; similar chemokine release after
      mediator stimulation was demonstrated, indicating that the two cell types are
      phenotypically similar.

PMID- 12792477
TI  - Does amniotic membrane transplantation improve the outcome of autologous limbal
      transplantation?
AB  - PURPOSE: To evaluate the additional benefits of amniotic membrane transplantation
      (AMT) when combined with conjunctival limbal autograft (CLAU) in the treatment of
      chronic chemical burns. METHODS: Thirty eyes of 30 rabbits underwent a chemical
      burn to create limbal deficiency. Forty-five days later, the animals were
      randomized into three groups of 10 rabbits each. Eyes from group 1 were treated
      with CLAU, group 2 underwent CLAU and AMT, and group 3 served as control without
      surgery. Corneal vascularization and opacity were documented with external
      photographs at postoperative days 30, 60, and 90. The rabbits were killed 3
      months after surgery, and their corneas divided into two halves. One half was
      prepared for hematoxylin-eosin and periodic acid-Schiff staining and the other
      for frozen sections and immunostaining with AM3 (to MUC 5AC mucin) and AE5 (to K3
      keratin). Final clinical outcome was also scored using external photographs at
      the last follow-up examination. RESULTS: After chemical burn, all groups showed
      similar degrees of conjunctivalization. After transplantation, corneal
      vascularization was worse in controls at 60 and 90 days (p < 0.001). At 30 days,
      eyes from group 1 had less corneal opacity (p < 0.05). At 90 days, corneal
      opacity was worse in controls but the same in groups 1 and 2 (p < 0.05). At the
      same time, limbal deficiency was significantly worse in controls (p < 0.05) but
      similar between groups 1 and 2. Corneal phenotype was present in 70% of the eyes
      in group 1, 50% in group 2, but in 10% of the controls. Clinical success with
      clear corneas was significantly more common in groups 1 and 2 when compared with
      controls (p < 0.001). CONCLUSIONS: CLAU is effective in treating limbal
      deficiency. The concurrent AMT does not add benefits in this rabbit model of
      chemical burns.

PMID- 12792478
TI  - Tumor necrosis factor inhibitor gene expression suppresses lacrimal gland
      immunopathology in a rabbit model of autoimmune dacryoadenitis.
AB  - PURPOSE: To evaluate the effect of tumor necrosis factor (TNF) inhibitor protein
      on lacrimal gland immunopathology and ocular surface disease resulting from
      induced dacryoadenitis. METHODS: Autoimmune dacryoadenitis was induced in rabbits
      by injecting the lacrimal glands with peripheral blood lymphocytes (PBLs)
      activated by 5 days of coculture with autologous acinar cells in a mixed cell
      reaction. In the treated group, an adenoviral vector carrying the TNF inhibitor
      gene (AdTNFRp55-Ig) was concurrently injected with AMCR-PBL. Tear production was
      monitored by Schirmer test, and tears were collected for detection of TNF
      inhibitor protein. Frozen sections of the glands were immunostained for
      expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), and CD18.
      Histological sections of lacrimal glands were examined using the TUNEL technique
      to monitor apoptosis. RESULTS: Soluble TNF-inhibitor protein was detected by
      ELISA in tears, with titers at a maximum on day 3, declining by day 7, and
      undetectable by day 14. Tear production declined in the induced dacryoadenitis
      group but did not change when glands had been treated with AdTNFRp55-Ig
      simultaneously with disease induction. Tear break-up time and rose bengal
      staining properties were not altered by treatment. Fourteen days after the glands
      were injected with activated PBLs, focal mononuclear cell infiltrates were
      observed around ducts and venules, some of which assumed the high endothelial
      phenotype, and between acini. Immune cells in the infiltrates stained positive
      for CD4, RTLA, and CD18. Glands that received AdTNFRp55-Ig concurrently with
      activated PBLs had decreased numbers of CD4 cells, CD18 cells, RTLA, and
      apoptotic cells. CONCLUSIONS: In vivo transduction of the lacrimal gland with
      AdTNFRIp55-Ig resulted in transient expression in the gland and the appearance of
      TNF-inhibitor protein in tears. The presence of soluble TNF-inhibitor protein
      partially suppressed the appearance of Sjogren's syndrome-like features of
      reduced tear production and the immunohistopathology associated with induced
      autoimmune dacryoadenitis but not tear break-up time and ocular surface disease.
      This may reflect immunoregulation in the lacrimal gland but not in the
      conjunctiva.

PMID- 12792479
TI  - Corneal endothelial cell damage from glaucoma drainage device materials.
AB  - PURPOSE: To compare the level of endothelial damage caused by contact with
      materials used in contemporary glaucoma drainage devices and a phosphorylcholine
      polymer-coated PMMA (PC-PMMA). METHODS Standard-sized discs of silicone, PMMA
      (polymethylmethacrylate), and PC-PMMA (n = 6) were gently lowered onto cultured
      bovine corneal endothelial (BCE) monolayers using a vacuum suction device. A 2.4
      g stainless steel cloning ring weight was then placed on top of each disc. The
      weights and discs were removed using a vacuum suction device and forceps after 5
      minutes of contact. A 0.4% trypan blue solution was used to stain the cell
      monolayer to visualize the area of cell damage. The total area of damage in each
      well (including the area stripped of cells) was measured using an image processor
      and expressed as a percentage of the total disc area to derive a damage
      coefficient for each material. Damage coefficients for different materials were
      compared using Bonferroni corrected analysis of variance (ANOVA). RESULTS:
      Percentage of areas of damage (mean +/- SD) after standardized contact were as
      follows: PMMA, 5.95 +/- 4.60%; silicone, 3.08 +/- 2.68%; PC-PMMA, 0.15 +/- 0.25%.
      PMMA caused marked endothelial cell damage. PC-PMMA discs produced a
      significantly lower level (p = 0.04) of endothelial cell trauma. CONCLUSION: Our
      results suggest that PC coating technology may be effective in reducing the rate
      of corneal endothelial failure following GDD implantation.

PMID- 12792480
TI  - Potentiation by cyclic AMP of the stimulatory effect of epidermal growth factor
      on corneal epithelial migration.
AB  - PURPOSE: To provide insight into the mechanism by which epidermal growth factor
      (EGF) stimulates corneal epithelial migration, we investigated the possible
      interaction between EGF and cyclic AMP (cAMP) signaling pathways during
      epithelial migration with an organ culture system for the rabbit cornea. METHODS:
      Rabbit corneal blocks were cultured in the absence or presence of various agents
      for 24 hours and were then fixed, dehydrated, embedded in paraffin, sectioned,
      and stained with hematoxylin-eosin. The path length of epithelial migration was
      measured on light micrographs of the stained sections. RESULTS: Epidermal growth
      factor alone stimulated corneal epithelial migration in a dose-dependent manner.
      In contrast, neither of two cell-permeable cAMP analogs, dibutyryl cAMP and 8
      bromo cAMP, affected epithelial migration at concentrations up to 1 mM. In the
      presence of EGF (10 ng/mL), however, each of the two cAMP derivatives increased
      the extent of epithelial migration in a concentration-dependent manner. Neither
      the adenylate cyclase activator forskolin nor the phosphodiesterase inhibitor 3
      isobutyl-1-methylxanthine alone affected epithelial migration. However, each of
      these two agents potentiated the stimulatory effect of EGF on this process. The
      stimulatory effects of fibronectin, hyaluronan, and interleukin-6 on corneal
      epithelial migration were not modified by either dibutyryl cAMP or 3-isobutyl-1
      methylxanthine. CONCLUSION: These results demonstrate that cAMP potentiates the
      stimulation of corneal epithelial migration by EGF in vitro, suggesting that
      endogenous cAMP might function as a modulator of epithelial wound healing
      promoted by this growth factor in vivo.

PMID- 12792481
TI  - Experimental anterior lens capsule transplantation for chronic corneal ulcers
      Bowman's layer replacement?
AB  - PURPOSE: This study was designed to measure the value of allografted anterior
      lens capsule in the reepithelialization of recurrent corneal ulcers. METHODS:
      Mechanical ulcers of uniform size were created with a 6-mm corneal trephine in
      both eyes of four Chinchilla male rabbits at one-third corneal depth. Following
      initial epithelial regrowth, an identical injury was created in the same area of
      each cornea a second time. In four eyes (treated group), an anterior lens capsule
      from a healthy donor rabbit was sutured into the ulcer bed followed by
      antibiotic/steroid drops three times daily for 1 week. The remaining four control
      eyes were allowed to heal without surgical intervention using the same
      antibiotic/steroid drops only. Slit-lamp examination and histopathology findings
      were recorded over a 6-month follow-up period. RESULTS: The four treated eyes
      reepithelialized after the second injury at a faster rate than the control group
      eyes and had a lower percentage of corneal opacification at all follow-up exam
      dates. Histopathology revealed normal epithelium overlying the transplanted
      anterior lens capsule and no infiltration of inflammatory cells in the
      subepithelial stroma. CONCLUSIONS: In experimental conditions,
      allotransplantation of anterior lens capsule speeds up reepithelialization after
      repeated mechanical trauma to the cornea. To our knowledge, this is the first
      experimental transplantation of an anterior lens capsule to create an artificial
      Bowman's layer in recurrent corneal ulcerations to aid reepithelialization and
      minimize corneal scarring.

PMID- 12792482
TI  - Assessment of transient changes in corneal hydration using confocal Raman
      spectroscopy.
AB  - PURPOSE: The degree of corneal hydration has been linked to excimer laser corneal
      ablation rates. Enhanced precision with excimer laser refractive surgery may
      result from a better understanding of the transient changes in corneal hydration.
      To better understand the dynamic nature of corneal hydration, bovine corneas were
      investigated under different surface treatments. METHODS: Confocal micro-Raman
      spectroscopy was used to quantify corneal hydration. Water and acetone solutions
      were used to establish a quantitative response of the relative OH/CH Raman bands,
      which are consistent with the water and collagen protein bands in cornea,
      respectively. Intact bovine corneas were manually debrided (designated MD group)
      or lamellar flaps were created to expose stromal tissue (designated lamellar
      keratectomy or LK group). Raman spectra were recorded every 30 seconds for 6
      minutes while the prepared cornea surfaces were exposed to quiescent air or to a
      forced nitrogen gas flow across the surface. RESULTS: The OH and CH Raman bands
      yielded a linear response while the percentage of acetone was varied from 0% to
      100%. For the bovine cornea under forced flow drying, the OH/CH Raman band ratio
      was found to decrease by 41% from the initial value for both the MD and LK
      treatment groups. These decreases were significantly more (p = 0.0051 and 0.054,
      respectively) than the 26% decrease in the OH/CH band ratio measured for the
      control corneas. In quiescent air, the control and MD groups exhibited a 7% and
      6% decrease in the OH/CH ratio, respectively, while the LK treatment group
      revealed a 19% decrease in the OH/CH ratio. CONCLUSIONS: The bovine eye
      experiments demonstrate that significant changes in corneal hydration are
      realized under different drying conditions and treatment methodologies. This
      study elucidates the nature of transient changes in corneal hydration in a bovine
      model and suggests the need for further study of the role of such variations in
      surgical outcome for excimer laser corneal refractive procedures.

PMID- 12792483
TI  - Sequestered viscoelastic after deep lamellar keratoplasty using viscodissection.
AB  - PURPOSE: Deep lamellar keratoplasty (DLKP) is an intricate procedure that
      preserves the host's endothelium, thus eliminating the possibility of endothelial
      graft rejection and potentially offering great benefits over penetrating
      keratoplasty. DLKP may be performed by a variety of techniques including
      viscodelamination, in which the stroma is separated from Descemet's membrane
      using viscoelastic. METHODS: Here we present an operative complication of this
      technique, which was not initially recognized, that caused significant morbidity
      to our patient and eventually led to the eye requiring a full thickness regraft.
      We also attempt to reproduce the lesion using nonviable cadaver corneas and
      illustrate histologically the nature of the corneal stroma and its relationship
      to Descemet's membrane following viscoelastic delamination.

PMID- 12792484
TI  - Bilateral microsporidial keratoconjunctivitis in an immunocompetent non-contact
      lens wearer.
AB  - PURPOSE: To describe an immunocompetent male with bilateral microsporidial
      keratoconjunctivitis who responded to treatment with albendazole, propamidine,
      and fumagillin. METHODS: Corneal and conjunctival epithelial scrapings from a man
      with bilateral keratoconjunctivitis previously treated with topical
      corticosteroids were evaluated by Gram stain and by fluorescence microscopy.
      RESULTS: Gram stain and fluorescence microscopy of corneal epithelial scraping
      revealed organisms characteristic of microsporidia. Results of human
      immunodeficiency virus antibody testing were reported as nonreactive. Symptoms of
      ocular discomfort and clinical signs of keratoconjunctivitis resolved after five
      weeks of treatment that included systemic albendazole and topical propamidine
      isethionate 0.1% and fumagillin bicyclohexylammonium salt. A follow-up
      conjunctival scraping failed to detect any residual organisms 2 weeks after
      cessation of all treatment. CONCLUSION: Microsporidial ocular infection occurred
      in an immunocompetent non-contact lens wearer. Microsporidial
      keratoconjunctivitis should be considered in any individual with atypical
      multifocal diffuse epithelial keratitis, regardless of immune status or recent
      history of contact lens wear.

PMID- 12792485
TI  - Bilateral corneal opacities associated with idiopathic multicentric osteolysis.
AB  - PURPOSE: To report unusual bilateral corneal opacity and inferior corneal
      thinning in a patient with idiopathic multicentric osteolysis. METHODS: A 17-year
      old girl with a history of idiopathic multicentric osteolysis was evaluated for
      corneal opacities. RESULTS: She was found to have bilateral, linear, posterior
      corneal opacity and inferior corneal thinning. Her vision did not appear to be
      affected. No progression of the corneal findings was noted over a period of 2
      years. CONCLUSION: Posterior corneal opacity and inferior corneal thinning may be
      associated with idiopathic multicentric osteolysis, a rare disorder of unknown
      etiology characterized by bony abnormalities and nephropathy. Patients with
      idiopathic multicentric osteolysis should be evaluated by an ophthalmologist for
      the presence of corneal opacities.

PMID- 12792486
TI  - Corneal decompensation after laser in situ keratomileusis in fuchs' endothelial
      dystrophy.
AB  - PURPOSE: To report corneal decompensation after laser in situ keratomileusis
      (LASIK) in a patient with Fuchs' endothelial dystrophy. METHODS: Observational
      case report. RESULTS: A 47-year-old woman with cornea guttata without symptoms or
      findings of corneal edema had uneventful LASIK for -5.50 -0.50 x 150 in the right
      eye and -4.00 -1.25 x 170 in the left eye. Postoperatively, she developed corneal
      edema, with significant loss of best-corrected visual acuity in both eyes.
      Preoperative corneal thickness was 587 microm in the right eye and 549 microm in
      the left eye, measured by ultrasound pachymetry. These readings were 550 and 560
      microm on day 67 postoperatively. Endothelial cell counts showed means of 1209
      and 1661 cells/mm2 in the right and left eyes, respectively. CONCLUSION: Caution
      is suggested when considering LASIK in eyes with severe cornea guttata.

PMID- 12792487
TI  - LASIK after epikeratophakia.
AB  - PURPOSE: To present a case of successful laser in situ keratomileusis (LASIK)
      performed on a patient with residual hyperopic astigmatism and symptomatic
      anisometropia after previous epikeratoplasty (epikeratophakia). METHODS: LASIK
      was used successfully to treat hyperopic astigmatism after regression of
      epikeratophakia performed 16 years earlier. RESULTS: Visual acuity improved to
      20/30 without correction, and best-corrected visual acuity was 20/25 at the 3
      month postoperative visit. CONCLUSIONS: LASIK can be used successfully as an
      alternative treatment to correct residual refractive error after epikeratoplasty.

PMID- 12792488
TI  - Penetrating keratoplasty and keratolimbal allograft transplantation for corneal
      perforations associated with the ectodermal dysplasia syndrome.
AB  - PURPOSE: To report two patients with ectodermal dysplasia-associated keratopathy
      treated with keratolimbal allograft transplantation and penetrating keratoplasty.
      METHODS: Two patients with ectodermal dysplasia suffered multiple corneal
      perforations. In both patients, keratolimbal allograft transplantation was
      performed along with penetrating keratoplasty. Histopathology of the corneal
      buttons was obtained. RESULTS: Histopathologic examination showed chronic
      inflammation with thin, irregular epithelium, loss of stromal tissue, and thin or
      absent Bowman's membrane. Both patients had multiple contributing factors
      predisposing them to corneal perforations including an inherent ectodermal
      defect, trichiasis, poor tear film, and limbal stem cell deficiency. CONCLUSIONS:
      Patients with keratopathy and corneal perforations associated with the ectodermal
      dysplasia syndrome has a poor prognosis. Keratolimbal allograft transplantation
      may have a role in the treatment of this disease. Longer follow-up and additional
      case reports will determine whether this technique confers a better prognosis
      than keratoplasty alone.

PMID- 12792489
TI  - Encephalocraniocutaneous lipomatosis: case report and review of the literature.
AB  - PURPOSE: Encephalocraniocutaneous lipomatosis is a congenital neurocutaneous
      syndrome characterized by lipomatous craniofacial hamartomas. The most common
      ocular manifestation is epibulbar choristoma, but many additional eye anomalies
      may be present. METHODS: To our knowledge, this is the first reported case with
      bilateral aniridia. We report a case of a boy affected by this syndrome and
      review the literature. CONCLUSION: Regarding this case, we suggest adding
      aniridia to the possible ocular anomalies in this syndrome.

PMID- 12792490
TI  - Use of voriconazole in Scedosporium apiospermum keratitis.

PMID- 12792491
TI  - The use of non-heart-beating donors for isolated pancreatic islet
      transplantation.
AB  - Recent improvements in isolated islet transplantation indicate that this therapy
      may ultimately prove applicable to patients with type I diabetes. An obstacle
      preventing widespread application of islet transplantation is an insufficient
      supply of cadaveric pancreata. Non-heart-beating donors (NHBDs) are generally not
      deemed suitable for whole-organ pancreas donation and could provide a significant
      source of pancreata for islet transplantation. Isolated pancreatic islets
      prepared from 10 NHBDs were compared with those procured from 10 brain-dead
      donors (BDDs). The success of the isolation for the two groups was analyzed for
      preparation purity, quality, and recovered islet mass. The function of NHBD and
      BDD islets was evaluated using in vitro and in vivo assays. On the basis of the
      results of this analysis, an NHBD isolated islet allograft was performed in a
      type I diabetic. The recovery of islets from NHBDs was comparable to that of
      control BDDs. In vitro assessment of NHBD islet function revealed function
      equivalent BDD islets, and NHBD islets transplanted to non-obese diabetic-severe
      combined immunodeficient (NOD-SCID) mice efficiently reversed diabetes.
      Transplantation of 446,320 islet equivalents (IEq) (8,500 IEq/kg of recipient
      body weight) from a single NHBD successfully reversed the diabetes of a type I
      diabetic recipient. Normally functioning pancreatic islets can be isolated
      successfully from NHBDs. A single donor transplant from an NHBD resulted in a
      state of stable insulin independence in a type I diabetic recipient. These
      results indicate that NHBDs may provide an as yet untapped source of pancreatic
      tissue for preparation of isolated islets for clinical transplantation.

PMID- 12792492
TI  - Human cytotoxic T lymphocytes specific for Wilms' tumor antigen-1 inhibit
      engraftment of leukemia-initiating stem cells in non-obese diabetic-severe
      combined immunodeficient recipients.
AB  - Leukemia is a disease characterized by the malignant transformation of
      hematopoietic stem cells. Previous studies have shown that the Wilms' tumor
      antigen-1 (WT1) transcription factor is expressed at elevated levels in
      hematopoietic stem cells of leukemia patients compared with normal stem cells. In
      the past, we have generated cytotoxic T lymphocytes (CTL) specific for WT1, and
      we have shown that they killed WT1-expressing leukemia cell lines and inhibited
      the in vitro colony-forming activity of leukemia cells of patients. We used a
      xenotransplantation model to address whether WT1-specific CTL can selectively
      inhibit engraftment of malignant but not normal stem cells. CD34+ hematopoietic
      cells isolated from individuals with chronic myeloid leukemia or normal
      hematopoiesis were treated with WT1-specific CTL and injected into
      immunodeficient non-obese diabetic-severe combined immunodeficient mice. After 5
      to 8 weeks, engraftment of leukemic or normal human cells was analyzed using
      immunohistology, flow cytometry, and polymerase chain reaction amplification of
      human sequences. The data showed that exposure of chronic myeloid leukemia CD34+
      cells to WT1-specifc CTL completely prevented the development of leukemia in the
      recipient mice, whereas CTL treatment did not inhibit engraftment of normal CD34+
      stem cells. The experiments indicate that WT1-specific CTL can discriminate
      between stem cells that give raise to leukemia and normal hematopoiesis in the
      xenogenic transplantation model. This supports the use of CTL with this
      specificity for treatment of leukemia patients undergoing stem-cell
      transplantation.

PMID- 12792493
TI  - Airway anastomotic dehiscence associated with use of sirolimus immediately after
      lung transplantation.
AB  - GOAL: The goal of this study was to assess the efficacy of sirolimus in lung
      transplant recipients. METHODS: The study was designed as a single center,
      consecutive case study of lung-transplant recipients treated with sirolimus,
      tacrolimus, and prednisone. All study subjects also received an HMG-CoA reductase
      inhibitor, and prophylaxis for cytomegalovirus and Pneumocystis carinii. RESULTS:
      A total of 15 subjects were enrolled in the study. Within 6 months, significant
      airway complications occurred in four subjects, three of whom died. At that
      point, the investigators terminated enrollment in the study. The study population
      was compared retrospectively with a group of 83 consecutive lung recipients
      treated with cyclosporine (n=64) or tacrolimus (n=19), mycophenolate mofetil, and
      prednisone. This confirmed an increased incidence of airway dehiscence and
      reduced survival in the sirolimus-treated patients. Sirolimus-treated patients
      had a low incidence of acute rejection. No significant differences were noted in
      the incidence of bacterial or fungal bronchopulmonary infections. CONCLUSIONS: We
      observed an unexpectedly high incidence of postoperative airway dehiscence in
      lung-transplant recipients treated with sirolimus, in combination with
      tacrolimus, prednisone, and an HMG-CoA inhibitor. Further studies will be needed
      to determine the safety and efficacy of using sirolimus after complete airway
      healing has occurred.

PMID- 12792494
TI  - Successful segmental auxiliary liver transplantation from a non-heart-beating
      donor: implications for split-liver transplantation.
AB  - BACKGROUND: Liver transplantation (LT) using grafts from non-heart-beating donors
      (NHBDs) has been shown to be a successful practice. Recently reported primary
      nonfunction rates are similar to those of LT using grafts from brain-dead donors.
      METHOD: We report the use of an NHBD liver, which was cut into a right-lobe graft
      and implanted as an auxiliary partial orthotopic liver transplant for acute liver
      failure in a 11-year-old child. The warm ischemia time was 21 minutes, and the
      cold ischemia was 8 hours. RESULTS: Initial graft function was excellent, and the
      child is well, with normal liver function 2 months posttransplant. CONCLUSION:
      Reduction and splitting of livers from NHBDs for transplantation is a realistic
      option, provided there is careful selection of the graft.

PMID- 12792495
TI  - Induction of operational tolerance to discordant dopaminergic porcine xenografts.
AB  - BACKGROUND: Porcine embryonic neural tissue transplanted intracerebrally could
      potentially relieve the symptoms of Parkinson's disease if the immune response
      toward the graft could be overcome. However, conventional immunosuppressive
      treatments have proven inefficient in preventing rejection. An alternative is
      blocking the costimulatory signals for lymphocyte activation. Treatment with
      cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA4Ig) and anti-CD40L has been
      successful in preventing rejection of xenografts in some experimental studies,
      but not all. Lymphocyte function antigen (LFA)-1 is an important costimulatory
      molecule for CD8+ T cells, and we hypothesize that blockade with anti-LFA-1 may
      enhance the efficacy of CTLA4Ig and anti-CD40L therapy. METHODS: C57BL/6 mice
      received intracerebral transplants of ventral mesencephalic tissue from embryonic
      porcine donors. CTLA4Ig, anti-CD40L, and anti-LFA-1 were administered every other
      day on days 0 to 8, and the transplants were studied after 4 to 6 weeks. Grafts
      were histologically analyzed for size, survival of dopaminergic nerve cells, and
      immune responses. Recipients were challenged with cultured glia cells of donor
      origin or an allogeneic skin graft to evaluate tolerance induction. RESULTS: Mice
      treated with all three substances had large grafts containing high amounts of
      dopamine cells but a low degree of immune response. Grafts in recipients
      challenged with glial cells showed an increased immunologic activity but were not
      rejected. Triple-treated mice showed a normal rejection process of the allogeneic
      skin grafts. CONCLUSION: After a short course of costimulation blocking therapy,
      discordant neural xenografts demonstrate long-term survival, withstand
      immunologic challenge, yet maintain host-versus-graft reactivity. Anti-LFA-1
      complements CTLA4Ig and anti-CD40L in the induction of operational tolerance to
      these xenografts.

PMID- 12792496
TI  - Combination therapy of malononitrilamide FK778 with tacrolimus on cell
      proliferation assays and in rats receiving renal allografts.
AB  - BACKGROUND: Malononitrilamide FK778, an analogue of leflunomide's active
      metabolite, is a promising novel small molecule with immunosuppressive and
      immunomodulatory properties. In this study, we evaluated the ability of
      combination therapy of FK778 with tacrolimus to inhibit lymphocyte proliferation
      and to prevent acute allograft rejection. METHODS: Proliferation assay was used
      to evaluate the effect of FK778 plus tacrolimus on murine splenocytes, monkey
      lymphocytes, and human peripheral blood mononuclear cells, after activation with
      T or B cell-specific mitogens. A rat kidney transplantation model was used to
      evaluate the ability of FK778 combined with tacrolimus to prolong allograft
      survival. Median-effect principle and combination index (CI) were used to
      determine synergism, summation, or antagonism. RESULTS: A total of 58
      combinations of FK778 plus tacrolimus were evaluated. Of the combinations tested,
      82.8% (24/29) produced additive to synergistic effects in B cells, whereas 79.3%
      (23/29) produced moderate antagonistic effects in T cells. A concomitant 14-day
      therapy of FK778 (10 mg/kg/day) and tacrolimus (1 mg/kg/day) synergistically
      prolonged renal allograft survival to 25.5+/-5.9 days (CI=0.458). However, when
      addition of FK778 to tacrolimus therapy was delayed to day 7 after
      transplantation, a strong synergism was obtained (mean survival time=74.9+/-14.8
      days, CI<0.001). CONCLUSIONS: This study demonstrates that the combination of
      FK778 with tacrolimus in vitro produces synergistic inhibition on B-cell
      proliferation but not on T cell proliferation in mice, nonhuman primates, and
      humans. When the addition of FK778 treatment was delayed to day 7 after
      transplantation, a strong synergism was produced in prolongation of renal
      allograft survival in the rat.

PMID- 12792497
TI  - Intestinal decontamination using povidone-iodine compromises small bowel storage
      quality.
AB  - BACKGROUND: Povidone-iodine (PI) (Betadine, Purdue Fredrick Co., Norwalk, CT) is
      used during pancreas transplantation to provide duodenal decontamination without
      any intestinal complications. METHODS: This study assessed the combined effect of
      a luminal pretreatment with PI followed by a proven amino acid (AA)-rich
      preservation solution on small bowel (SB) storage quality. Rat SB was procured
      using intra-arterial University of Wisconsin solution followed by luminal
      administration with combinations of AA+/-PI pretreatment as follows: group 1, 20
      mL AA solution; group 2, 20 mL PI and 20 mL AA solution; group 3, 100 mL AA
      solution; and group 4, 20 mL PI and 100 mL AA solution. Cellular energetics,
      permeability, and histology were analyzed throughout 10-hr cold storage. RESULTS:
      After 10 hr, adenosine triphosphate levels remained 2.9 to 3.2 micromol/g protein
      lower in the PI-treated groups than in groups 1 and 3. Functional parameters were
      also negatively affected by PI treatment. Mannitol permeability was 203 and 66
      nmol/cm2 per hr in groups 2 and 4 versus 46 and 44 nmol/cm2 per hr in groups 1
      and 3. Median grades of histologic injury (Park's) at 10 hr were 3, 5.5, 4, and 5
      for groups 1 through 4, respectively. Luminal flushing with PI or AA solution
      resulted in an equivalent clearance greater than 95% of enteric bacteria present.
      CONCLUSIONS: hort-duration luminal PI exposure potentiates SB injury and provides
      no improved intestinal decontamination.

PMID- 12792498
TI  - APC0576: a novel small molecule, immunosuppressive agent effective in primate
      models.
AB  - BACKGROUND: APC0576, 5-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)
      2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine is a novel synthetic
      compound with an inhibitory activity on NF-kappaB-dependent gene activation and
      chemokine synthesis in human endothelial cells. This article describes the effect
      of APC0576 on T-cell-dependent immune functions in vitro and in vivo in primate
      models, because NF-kappaB is known to be one of the potent mediators in T-cell
      activation. METHODS: The effects of APC0576 on interleukin-2 production and
      proliferative responses in human peripheral blood mononuclear cells were studied
      under various stimuli with in vitro culture assay. Next, female rhesus monkeys
      were immunized with tetanus toxoid (TTx), and APC0576 was orally administered for
      4 weeks. Serum-specific antibody for TTx was monitored weekly using an enzyme
      linked immunosorbent assay, and delayed-type hypersensitivity reaction was
      examined after 4 weeks of APC0576 treatment. To evaluate the immunosuppressive
      activity, APC0576 was orally administered for 32 days to rhesus monkeys that
      received transplants of allogeneic kidney. RESULTS: APC0576 effectively
      suppressed interleukin-2 production and proliferation in activated human
      peripheral blood mononuclear cells. Both delayed-type hypersensitivity reaction
      and specific antibody formation evoked by TTx was significantly and dose
      dependently attenuated by 4 weeks treatment of APC0576 without any serious
      toxicologic signs. Allogeneic kidneys grafted in rhesus monkeys were not rejected
      and fully functioned during the 32 days of APC0576 treatment, although they were
      rapidly rejected after the withdrawal of the drug. CONCLUSIONS: A novel, orally
      available immunosuppressive agent, APC0576, effectively inhibited T-cell-based
      immune responses both in vitro and in vivo. APC0576 may have potential for a
      therapeutic agent in clinical organ transplantation and various cytokine-mediated
      diseases.

PMID- 12792499
TI  - FTY720 reduces T-cell recruitment into murine intestinal allograft and prevents
      activation of graft-infiltrating cells.
AB  - BACKGROUND: Effective immunosuppression is a critical determinant of graft
      survival in small-bowel transplantation (SBTx). The present study was designed to
      determine the potency of FTY720, a newly synthesized immunosuppressant, in rat
      SBTx and examine the phenotype of graft-infiltrating cells to evaluate its effect
      on intestinal allografts. MATERIALS AND METHODS: A segment of intestine of Dark
      Agouti rats was transplanted heterotopically into Lewis rats. The recipients were
      treated with or without oral FTY720 at a dose of 1 mg/kg per day. Six days after
      surgery, peripheral blood lymphocytes and lymphocytes from the mesenteric lymph
      nodes, Peyer's patches, intraepithelial site, and lamina propria of the
      intestinal allograft were isolated. After the number of lymphocytes in each site
      was counted, the lymphocyte subpopulations in the intestinal allograft were
      evaluated by means of a FACScan flow cytometer using several monoclonal
      antibodies. RESULTS: FTY720 treatment significantly prolonged recipient survival
      and strongly inhibited rejection histologically in comparison with control rats.
      FTY720 immunosuppression resulted in a marked reduction of lymphocyte number in
      the graft epithelium and lamina propria and the proportion of CD8+ and CD25+
      cells. FTY720 also significantly decreased T-cell receptors and increased B cells
      in the graft Peyer's patches. CONCLUSION: FTY720 promoted long-term SBTx
      recipient survival and maintained the architecture of intestinal allografts.
      FTY720 immunosuppression may be associated with a reduction of T-cell recruitment
      subsequent to the redistribution of lymphocyte subpopulations to control the
      proliferation and activation of graft-infiltrating cells in intestinal
      allografts.

PMID- 12792500
TI  - Attenuation of acute xenograft rejection by short-term treatment with LF15-0195
      and monoclonal antibody against CD45RB in a rat-to-mouse cardiac transplantation
      model.
AB  - BACKGROUND: We previously reported that Lewis rat hearts transplanted into BALB/c
      mice developed typical acute vascular rejection (AVR). The present study was
      undertaken to determine the efficacy of LF15-0195, a new analogue of 15
      deoxyspergualin, in the prevention of AVR and to determine whether a combination
      of LF15-0195 and CD45RB monoclonal antibody (mAb) would have a synergistic effect
      in prolonging xenograft survival. METHODS: We transplanted 2-week-old Lewis rat
      hearts into BALB/c mice, followed by experimental immunosuppressive regimens.
      Control groups were either untreated or treated with mAb monotherapy (100
      microg/mouse, days -1 to 7, intravenously). Experimental groups were either
      treated with LF15-0195 (2 mg/kg, days -1 to 14, subcutaneously) or with LF15-0195
      combined with mAb at monotherapeutic doses. RESULTS: Heart xenografts in both
      untreated and mAb-treated BALB/c recipients were rejected at 6.0+/-0.7 days and
      8.5+/-1.3 days, respectively, with typical features of AVR, characterized by
      hemorrhage, fibrin deposition, thrombosis, and massive accumulations of anti-rat
      IgG and IgM. Serum xenoreactive antibodies (xAbs) were also markedly elevated in
      these animals. In contrast, LF15-0195 monotherapy significantly prolonged graft
      survival to 19.3+/-0.7 days. Notably, xAbs were significantly decreased and graft
      rejection was of a cell-mediated nature instead of AVR. When mAb was combined
      with LF15-0195, graft survival was further increased to 65.2+/-9.1 days. Antibody
      production and T-cell infiltration were significantly inhibited at terminal
      stages of graft survival. Sequential studies on days 6 and 14 demonstrated that
      LF15-0195, either alone or combined with mAb, completely inhibited antibody
      production. However, intragraft infiltration by Mac-1+ cells in LF15-0195-treated
      recipients was similar to that of untreated recipients. CONCLUSIONS: LF15-0195
      effectively attenuated AVR by markedly inhibiting antidonor xAb production.
      Treatment with a combination of LF15-0195 and CD45RB mAb also significantly
      reduced T-cell infiltration and should be studied further to evaluate its
      efficacy in nonhuman primate subjects.

PMID- 12792501
TI  - Liver transplantation for hepatopulmonary syndrome: a ten-year experience in
      Paris, France.
AB  - BACKGROUND: Although the possibility of reversing hepatopulmonary syndrome (HPS)
      after liver transplantation is now well established, the proportion of patients
      in whom reversibility is observed and the time to resolution of HPS remain
      uncertain. METHODS: We analyzed the outcome of all adult patients with HPS who
      underwent orthotopic liver transplantation in all the liver transplant centers in
      Paris, during a 10-year period. RESULTS: Twenty-three adult patients (median age,
      47 years; range, 14-64) underwent transplantation in four institutions. Median
      PaO(2) was 52 (range, 32-67) mm Hg and median alveolar-arterial oxygen gradient
      was 66 mm Hg. When patients were breathing 100% O(2), median PaO(2) was 310
      (range, 74-663) mm Hg. Median isotopic shunt ratio was 33% (range, 0-80%). The
      overall mortality during the study period was 30.5% (7/23). Perioperative
      mortality was 8.5%, whereas late mortality was 22%. None of the preoperative
      characteristics of HPS (isotopic shunt ratio, PaO(2) on room air or on 100%
      oxygen) was associated with overall postoperative mortality. Of the 21 patients
      surviving the perioperative period (median follow-up, 17 months; range, 0.5-72),
      a decrease in alveolar-arterial oxygen gradient of at least 5 mm Hg and at least
      10 mm Hg was observed in 21 of 21 and in 18 of 21 patients, respectively, with
      great variations in the time of improvement. The threshold of 70 mm Hg was
      reached in 15 patients. The lower the preoperative PaO(2), the longer the time to
      reach this point. CONCLUSION: Our data strongly support the role of orthotopic
      liver transplantation in adult patients with HPS, regardless of its severity.

PMID- 12792502
TI  - Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal
      allograft survival of patients with acute humoral rejection.
AB  - BACKGROUND: Acute humoral rejection (AHR) has been associated with enhanced graft
      loss. Our study compared the renal allograft survival of patients with AHR
      treated with plasmapheresis (PP) and intravenous immunoglobulin (IVIG) with
      allograft survival in patients with acute cellular rejection (ACR). METHODS: We
      retrospectively analyzed all kidney transplants performed at our institution
      between January 1999 and August 2001 (n=286). Recipients were classified into
      three groups according to biopsy reports: AHR, ACR, or no rejection. The ACR
      group was further divided into early and late rejection (<90 and >90 days
      posttransplant, respectively). RESULTS: After a mean follow-up of 569+/-19 days,
      the incidence of AHR was 5.6% (n=16). Recipient presensitization, delayed graft
      function, early rejection, and higher creatinine at diagnosis were characteristic
      of AHR. Most AHR patients (14/16) were treated with PP and IVIG. One patient
      received only IVIG, whereas another received only PP. All AHR patients were given
      steroid pulses, but only four received antilymphocyte therapy because of
      concomitant severe ACR. The ACR group comprised 43 patients (15%). One patient
      with mild rejection received no therapy, 20 improved with steroids alone, and 22
      required additional antilymphocyte therapy. One-year graft survival by Kaplan
      Meier analysis was 81% and 84% in the AHR and ACR groups, respectively (P=NS).
      Outcomes remained similar when AHR patients were compared with those with early
      ACR. CONCLUSIONS: We conclude that AHR, when diagnosed early and treated
      aggressively with PP and IVIG, carries a short-term prognosis that is similar to
      ACR.

PMID- 12792503
TI  - The influence of Duffy blood group on renal allograft outcome in African
      Americans.
AB  - BACKGROUND: African American patients demonstrate higher rates of acute allograft
      rejection and lower kidney-graft survival compared with white patients. Duffy
      antigen receptor for chemokines (DARC) on red blood cells has been suggested to
      have an anti-inflammatory role by acting as a "chemokine sink." We investigated
      the relationship of Duffy blood group type to renal allograft outcome in African
      American patient population. METHODS: A total of 163 African American kidney
      transplant recipients were studied for Duffy blood group status. Patient outcomes
      were assessed at 6 to 42 months after transplantation and monitored for acute
      rejection episodes, graft function, and graft survival. RESULTS: A total of 117
      (71.8%) patients were Duffy (a-b-), 14 (8.6%) Duffy (a+b-), 21 (12.9%) Duffy (a
      b+), and 11 (6.8%) Duffy (a+b+). No significant differences were observed among
      the groups with respect to median serum-creatinine values or the incidence of
      biopsy-confirmed acute-rejection episodes. Although only 15.4% of the patients
      had Duffy (a+) antigen, none lost their allograft during the study period, and
      Kaplan-Meier graft survival was not significantly different compared to Duffy (a
      ) group (log-rank test, P=0.12). Duffy (a-b-) patients demonstrated lower
      allograft survival compared with the other three groups, although statistical
      significance was not reached (log-rank test P=0.15). Delayed graft function (DGF)
      was strongly associated with graft failure for only Duffy (a-b-) patients (log
      rank test P=0.003). CONCLUSIONS: Duffy (a-b-) patients have lower allograft
      survival in the presence of DGF. DARC may attenuate the inflammatory effects of
      DGF by acting as a "chemokine sink," and DARC-negative patients may be more
      vulnerable to DGF.

PMID- 12792504
TI  - A prospective, randomized clinical trial of cyclosporine reduction in stable
      patients greater than 12 months after renal transplantation.
AB  - BACKGROUND: For stable kidney-transplant recipients receiving triple drug therapy
      with cyclosporine (CsA), prednisone, and mycophenolate mofetil (MMF), it remains
      unclear what is the optimal dose of CsA beyond the first 6 to 12 months after
      transplantation. Complete CsA withdrawal has been associated with a significant
      incidence of acute rejection and, in some studies, chronic rejection as well.
      METHODS: We performed an open, prospectively randomized, controlled clinical
      trial to determine whether CsA could be safely reduced by 50%. At 1 year or more
      posttransplant, 64 patients were randomized to either continue their stable
      maintenance CsA dose (control group, n=32) or to lower their CsA dose by 50% over
      a 2 month period (CsA reduction group, n=32). All patients had stable renal
      allograft function at the time of enrollment. RESULTS: Within 6 months of
      randomization, no episode of acute rejection or graft loss occurred in either
      group. Patients in the CsA reduction group had a slight but significant increase
      in their glomerular filtration rate and a trend towards lower serum creatinine.
      There was also a significant decrease in mean systolic blood pressure,
      triglycerides, and serum uric acid levels in the CsA reduction group. No
      significant changes in any of these parameters were observed in the control
      group. CONCLUSIONS: This study suggests that a strategy consisting of a 50% CsA
      reduction is safe and is not associated with the increased risk of acute
      rejection observed in CsA withdrawal studies. It also has the potential to
      improve short-term allograft function and appears to reduce cardiovascular risk
      factors such as hypertension and hyperlipidemia.

PMID- 12792505
TI  - The economic impact of laparoscopic living-donor nephrectomy on kidney
      transplantation.
AB  - BACKGROUND: End-stage renal disease accounts for $17.9 billion annually in direct
      medical costs in the United States. This study assessed the flow of expenditures
      from a Medicare perspective for laparoscopic donor nephrectomy compared with
      living and cadaveric transplantation and continued dialysis. METHODS: This study
      involved a nonrandomized, retrospective investigation of patients with end-stage
      renal disease and charges using institutional and physician/supplier charges from
      the United States Renal Data System. The subjects were classified as laparoscopic
      living-donor transplant, living-donor transplant, cadaveric transplant, or
      dialysis patients. The first treatment date was set as the index date, and
      monthly charges were plotted from 12 months before and up to 48 months after the
      index date. RESULTS: There were 230,769 dialysis patients and 44,063 transplant
      patients (181 laparoscopic living-donor, 11,466 living-donor, and 32,416
      cadaveric). Monthly institutional charges were similar in the year preceding the
      index date, but they were higher for transplantation in the month after the index
      date and lower in subsequent periods. Two-year post-index cumulative charges were
      as follows: Monthly institutional charges were similar for the living-donor
      ($191,374) and laparoscopic living-donor ($192,053) transplant patients, followed
      by the cadaveric transplant ($229,449) and dialysis ($250,348) patients, whereas
      physician/supplier charges were highest for the laparoscopic living-donor
      transplant ($104,583) patients, followed by the dialysis ($73,730), cadaveric
      transplant ($70,369), and living-donor transplant ($65,897) patients. The break
      even points for the living-donor, laparoscopic living-donor, and cadaveric
      transplant patients compared with the dialysis patients were 10, 14, and 18
      months, respectively. CONCLUSIONS: The laparoscopic procedure may be a beneficial
      alternative to the conventional open donor nephrectomy procedure and cadaveric
      transplantation, and it provides considerable benefits compared with dialysis.

PMID- 12792506
TI  - Alemtuzumab (Campath-1H) combined with tacrolimus in intestinal and multivisceral
      transplantation.
AB  - BACKGROUND: We combined alemtuzumab (Campath-1H, Berlex Laboratories, Montville,
      NJ) and tacrolimus (Tac) immunosuppression for intestinal and multivisceral
      transplantation. MATERIALS AND METHODS: A total of 21 adult patients received 24
      grafts: 14 intestinal, nine multivisceral, and one liver-intestinal graft.
      Alemtuzumab was administered perioperatively in four doses with low-dose Tac
      (levels 10-15 ng/dL) and no maintenance steroids. Tac was substituted with
      sirolimus in case of Tac-related complications. Suspected or mild rejections were
      treated with steroids. Moderate rejections were treated with steroids or OKT3.
      Severe rejections were treated with OKT3. RESULTS: Of the 16 patients that were
      followed up for an average of 9 months, 12 are alive with functioning grafts. Two
      patients experienced severe rejection, three experienced moderate rejection
      episodes, and seven experienced mild acute rejection episodes. Four patients
      never developed acute rejection. Infectious complications included a
      cytomegalovirus enteritis and four fungal infections (related to central venous
      access). CONCLUSIONS: The combination of alemtuzumab and Tac therapy without
      steroid use seems to efficiently prevent acute rejection in a significant number
      of patients without causing frequent opportunistic infections.

PMID- 12792507
TI  - Factors associated with ambivalence about bone marrow donation among newly
      recruited unrelated potential donors.
AB  - BACKGROUND: Previous research has indicated that feelings of ambivalence about
      donation are associated with donors' decisions not to donate and with less
      positive physical and psychosocial outcomes among donors who donated despite
      feeling ambivalent. The current study examines the prevalence of ambivalence
      among newly recruited potential bone marrow donors and identifies factors
      associated with greater ambivalence. METHODS: Using a cross-sectional design,
      questionnaires were mailed to a stratified random sample of individuals newly
      recruited to the National Marrow Donor Program registry at 71 local donor
      centers. A total of 426 new recruits (63%) completed and returned the
      questionnaire. RESULTS: Bivariate analyses indicated that multiple recruitment
      experience and donor perception variables were significantly associated with
      ambivalence. Multivariate analysis revealed that the following eight variables
      were uniquely associated with higher levels of ambivalence after adjusting for
      the effects of other key indicators: participating in other volunteer activities,
      joining at a drive for a specific patient, perceiving the recruitment staff as
      less informative, being discouraged from joining by others, not having an
      intrinsic commitment to donate, being encouraged by one's culture or religion to
      join, believing there are risks to donation, and having a greater number of
      medical, work, and family concerns about donation. CONCLUSIONS: Potential donors
      who are motivated by an intrinsic commitment to donate, rather than extrinsic
      pressure, are less ambivalent about donating. In addition, recruitment staff have
      a potentially critical role in reducing ambivalence among new recruits by
      providing information that may allay any unrealistic concerns recruits may have
      about the medical risks and impact of donation on work and family.

PMID- 12792508
TI  - Improved human islet isolation outcome from marginal donors following addition of
      oxygenated perfluorocarbon to the cold-storage solution.
AB  - Last year, from the approximately 6,000 organ donors, only approximately 1,500
      pancreata were used for clinical transplantation. Factors that contribute to this
      poor pancreas use include strict donor selection criteria and the requirement for
      short cold-ischemia time (CIT). Numerous pancreata have not been used because of
      long ischemia times postprocurement. Given the oxygen-rich environment of the
      islets in the native pancreas, it is conceivable that islets are highly
      susceptible to irreversible damage following prolonged ischemia. The use of
      continuously oxygenated perfluorohydrocarbons (PFCs), known for their high oxygen
      solubility coefficients, in a two-layer culture with standard University of
      Wisconsin preservation media, has extended the acceptable range CIT, and,
      furthermore, there has been no evidence of adverse effects from PFCs on the
      outcome of transplanted cells, whereas they often enhance islet cell function.
      The purpose of this study was to use the two-layer culture method to improve
      donor-organ use from marginal donors. Fifteen organs were procured using the two
      layer method, and 18 without using it, from donors greater than 50 years of age.
      Despite nonsignificant differences in age, weight of the donors, weight of the
      organ and CIT, the PFC group yielded an average of twofold more islet equivalents
      than those harvested from the control group. As a result, from the control group,
      only 2 of 18 organs were used for clinical islet transplantation, whereas 8 of 15
      were used from the PFC group. To this end, the two-layer method may help
      clinicians overcome the problem of organ underuse.

PMID- 12792509
TI  - A new epitope-based HLA-DPB matching approach for cadaver kidney retransplants.
AB  - BACKGROUND: Several years ago a significant impact of matching for HLA-DPB1
      alleles on the survival of cadaver kidney retransplants was shown. Here we report
      the results of a new approach, based on matching for HLA-DPB1 epitopes. METHODS:
      The analysis is based on 1,478 patients who received a cadaver kidney
      retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction,
      sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope
      matching was facilitated with the aid of sequence databases and computer
      calculations. RESULTS: Matching for the HLA-DP epitopes A, B, E, and F,
      corresponding to the homonymous hypervariable regions of the second exon of the
      DPB1 gene, seems to have a greater influence on graft survival than matching for
      the epitopes C and D. Within a group of 529 retransplants with exactly one
      allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when
      less than two epitope mismatches were found, compared with the group with more
      than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P=0.0112).
      Importantly, patients with two DPB1 allele mismatches who had less than or equal
      to two epitope mismatches exhibited a significantly better graft outcome than
      recipients who had one HLA-DPB1 allelic mismatch but more than three epitope
      mismatches (at 2 years: 77.1% vs. 65.8%, P=0.0488). CONCLUSIONS: The findings
      indicate that the impact of HLA-DPB1 matching on the outcome of kidney
      retransplants is a result of the predominant immunogenicity of certain epitopes
      of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be
      functionally more relevant than classical matching at the allelic level.

PMID- 12792510
TI  - The role of self-expandable metallic stents for the treatment of airway
      complications after lung transplantation.
AB  - BACKGROUND: Airway complications continue to be an important source of morbidity
      and mortality after lung transplantation (LTx). Different approaches have been
      used for their nonsurgical management. We describe our experience using self
      expandable metallic stents (SEMSs) in patients with airway complications post
      LTx. METHODS: We present a retrospective analysis of stent related-data of all
      the LTx patients who received SEMSs to treat postoperative airway complications.
      RESULTS: Between January 1992 and December 2001, 36 of 253 patients (14.2%)
      developed post-LTx airway complications involving 40 of 348 anastomoses (11.5%).
      A total of 15 SEMSs were placed in 12 patients (mean age 47.3+/-9.6 years) for
      tracheobronchomalacia, stenosis, and anastomotic dehiscence, including one
      patient referred from an outside hospital. Mean follow-up was 20.1+/-19.5 months
      (range 1.2-58 months). Patency and symptom improvement were achieved in 11 of 12
      patients. Stenting of the airway led to successful weaning of two patients who
      were on prolonged mechanical ventilation. Suture dehiscence was effectively
      managed in two patients who were not candidates for surgical repair. Overall, the
      complication rate was 0.040 complications per patient per month (total number of
      complications and total number of months using the stent). Bacterial bronchitis
      (four patients) and obstructive granulomas (three patients) were the most
      frequent complications. The survival of LTx patients with airway SEMSs was
      similar when compared with the survival of all other LTx patients (P=0.74).
      CONCLUSIONS: SEMSs are safe and effective in the management of airway
      complications in selected patients post-LTx. Weaning from mechanical ventilation
      and management of anastomotic dehiscence are the unique attributes of this
      device.

PMID- 12792511
TI  - Cytomegalovirus viremia associated with death or retransplantation in pediatric
      lung-transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a frequent complication of lung
      transplantation. However, there is limited information regarding the incidence
      and sequelae of CMV infections in pediatric lung-transplant recipients. On the
      basis of case series suggesting that CMV infection was associated with excess
      morbidity and mortality in lung-transplant recipients, we hypothesize that CMV
      viremia increases the risk of bronchiolitis obliterans (BOS) or death and
      retransplantation in the first year following transplantation. METHODS: A case
      cohort study of pediatric primary lung-transplant recipients was performed.
      Univariate analysis was used to assess whether CMV viremia was associated with
      BOS or death and retransplantation within 1 year after transplantation. Patients
      at high risk for CMV infection received ganciclovir prophylaxis for 42 days
      posttransplantation. RESULTS: From July 1990 to November 2000, 194 pediatric
      patients received primary lung transplants. Twenty-three percent of patients
      developed CMV viremia. Eighty percent of CMV viremia episodes occurred before 120
      days posttransplant. A first episode of CMV viremia was associated with
      retransplantation or death between days 90 and 365 (RR=4.1, 95% confidence
      interval [CI] 1.1-14.5) and was not associated with BOS (RR=1.3, 95% CI 0.5-3.3).
      CONCLUSIONS: CMV viremia in the first year after pediatric primary lung
      transplantation is associated with increased risk of death or retransplantation
      between 90 and 365 days posttransplant, when CMV prophylaxis has stopped. A phase
      II pilot trial is warranted to assess safety and short-term efficacy of
      increasing the duration of CMV prophylaxis from 42 to 120 days.

PMID- 12792512
TI  - Epidemiology of systemic mycoses among renal-transplant recipients in India.
AB  - BACKGROUND: Systemic mycoses have a high impact on tropical renal-transplant
      recipients. METHODS: Data from 1,476 primary renal-transplant recipients was
      prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence
      of systemic mycoses, its time of occurrence, risk factors, outcome, and
      postmortem findings in 30 patients with systemic mycoses were analyzed. RESULTS:
      A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal
      genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45%
      localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and
      chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB)
      with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was
      associated with nearly a 4-fold risk of systemic mycoses less than 6 months from
      the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA)
      therapy. Overall, the probability of survival with systemic mycoses was 73.4%,
      60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic
      mycoses at 1, 2, 5, and 10 years, respectively (P<0.0001). An extended Cox model
      with time-independent and dependent covariates showed greater than 15 times the
      risk of death among those who develop systemic mycoses. Similarly,
      Posttransplantation (postTX) TB+/-Nocardiosis, preTX TB, CMV disease, diabetes
      mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA
      immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk
      for death, respectively, as compared with those who did not have those risk
      factors. CONCLUSIONS: There is a recent predominance of Aspergillus among the
      transplant recipients. The risk factors for systemic mycoses are CMV disease,
      chronic liver disease, and hyperglycemia, and TB is an important coinfection.
      Systemic mycoses increased in the early postTX period with CsA. The risk factors
      for death are systemic mycoses, CMV disease, chronic liver disease (>40 months),
      diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the
      probability of survival with systemic mycoses was poor; however, survival has
      recently improved.

PMID- 12792514
TI  - Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is
      coincident with long-term recovery from posttransplant lymphoma after adoptive
      immunotherapy.
AB  - BACKGROUND: Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T
      lymphocytes (CTLs) has been used to treat EBV-induced posttransplant
      lymphoproliferative disease (PTLD) in solid-organ recipients. This study defines,
      in detail, the temporal relationship between adoptive transfer and the clinical
      response, EBV DNA load, and CTL response to EBV latent and lytic antigens in a
      patient with a subcutaneous PTLD presentation treated with adoptive transfer of
      autologous CTL. METHODS: A heart transplant patient developed multiple
      subcutaneous PTLD deposits and was treated with a total of six doses (20 x 106
      CTL per dose) of cultured autologous polyclonal EBV-specific CTL by adoptive
      transfer. RESULTS: Complete regression occurred after the sixth CTL dose, and the
      patient has remained disease-free from 47 weeks to the present (136 weeks). Real
      time polymerase chain reaction analysis showed a reduction in viral load after
      therapy. Enzyme-linked immunospot analysis using defined EBV CTL epitopes showed
      that the CTL precursor frequency (pCTL) toward a lytic antigen epitope was
      elevated early in the course of disease but tended to decrease to lower levels
      after long-term regression of PTLD. The most dramatic result was seen in relation
      to three latent CTL epitopes studied. Long-term regression of PTLD was
      characterized by high pCTL toward the latent antigens. CONCLUSIONS: Increased
      pCTL reactivity to latent EBV CTL epitopes is coincident with recovery from
      disease after adoptive transfer of autologous CTL. Furthermore, the results are
      compatible with the belief that activation of a sustained CTL response to EBV
      latent epitopes is protective and may be a characteristic of patients in long
      term remission from PTLD.

PMID- 12792513
TI  - Vitamin supplementation reduces the progression of atherosclerosis in
      hyperhomocysteinemic renal-transplant recipients.
AB  - BACKGROUND: We previously demonstrated among renal-transplant recipients (RTRs) a
      high prevalence of hyperhomocysteinemia, which might account for their elevated
      cardiovascular risk. The purpose of our study was to document, in
      hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid
      intima-media thickness (cIMT), which is an early sign of atherosclerosis.
      METHODS: A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to
      vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin
      B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All
      subjects underwent cardiovascular risk-factor assessment, including fasting
      homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure
      the intima-media thickness of common carotid arteries, at time of enrollment and
      after 6 months. RESULTS: Fasting Hcy levels markedly decreased in group A after
      treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001),
      whereas no significant changes were observed in group B (20.5 [17-37.6]
      micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT
      significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm;
      P<0.0001). All except one patient showed a reduction of cIMT and the mean
      percentage of cIMT decrease was -32.2+/-12.9%. Patients with
      methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy
      levels, had the major percentage of decrease of Hcy with respect to the other
      genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/-
      56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation
      (group B) we documented a significant increase in cIMT after 6 months (0.71+/
      0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase
      in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT
      increase was + 23.3+/-21.1%. CONCLUSIONS: Our results demonstrate a beneficial
      effect of the treatment of hyperhomocysteinemia by vitamin supplementation on
      cIMT in a group of RTRs.

PMID- 12792515
TI  - Accurate preoperative estimation of liver-graft volumetry using three-dimensional
      computed tomography.
AB  - BACKGROUND: The aim of this study was to clarify the value of three-dimensional
      computed-tomography (3D-CT) volumetry for size matching in living-donor liver
      transplantation (LDLT). METHODS: 3D-CT volumetry was applied to 25 donors who
      underwent hepatectomy for a living relative needing an orthotopic liver
      transplantation. Fifteen patients underwent extended left lobectomy, one patient
      an extended left lateral lobectomy, and nine patients right lobectomy. 3D-CT
      imaging was performed with the workstation ZIO M900 (Zio Software Inc., Tokyo,
      Japan). The estimated volume of the grafts in two-dimensional (2D) and 3D images
      were compared, and an error ratio was calculated. RESULTS: 3D-CT imaging revealed
      the anatomy of the hepatic vein bifurcation and the shape of the graft. The error
      ratio was 12.8+/-2.3% in 3D, compared with 19.4+/-2.5% in 2D. As such, 3D-CT
      volumetry appears to be more exact than conventional 2D-CT volumetry, but
      volumetry by 3D-CT still produces an error ratio of approximately 13%. The weight
      transition of the rats' livers under preservation in University of Wisconsin (UW)
      solution indicated that the graft volume seems to decrease during perfusion with
      UW solution. Mismatch of the cutting line and volume reduction by dehydration
      (approximately 5% reduction 1 hour after perfusion) seems to cause the error in
      3D-CT volumetry. CONCLUSIONS: Three-dimensional CT volumetry is useful for size
      matching in cases of living-related orthotopic liver transplantation.

PMID- 12792516
TI  - Serine proteinase inhibitor-9, an endogenous blocker of granzyme B/perforin lytic
      pathway, is hyperexpressed during acute rejection of renal allografts.
AB  - BACKGROUND: Serine proteinase inhibitor (PI)-9 with a reactive center P1 (Glu)
      P1' is a natural antagonist of granzyme B and is expressed in high levels in
      cytotoxic T lymphocytes (CTL). In view of the role of CTL in acute rejection, we
      explored the hypothesis that PI-9 would be hyperexpressed during acute rejection.
      Because PI-9 can protect CTL from its own fatal arsenal and potentially enhance
      the vitality of CTL, we examined whether PI-9 levels correlate with the severity
      of rejection as well as predict subsequent graft function. METHODS: We obtained
      95 urine specimens from 87 renal allograft recipients. RNA was isolated from the
      urinary cells and mRNA encoding PI-9, granzyme B, or perforin and a
      constitutively expressed 18S rRNA was measured with the use of real-time
      quantitative polymerase chain reaction assay, and the level of expression was
      correlated with allograft status. RESULTS: The levels of PI-9 (P=0.001), granzyme
      B (P<0.0001), and perforin mRNAs (P<0.0001), but not the levels of 18S rRNA
      (P=0.54), were higher in the urinary cells from the 29 patients with a biopsy
      confirmed acute rejection than in the 58 recipients without acute rejection. PI-9
      levels were significantly higher in patients with type II or higher acute
      rejection changes compared with those with less than type II changes (P=0.01).
      Furthermore, PI-9 levels predicted subsequent graft function (r=0.43, P=0.01).
      CONCLUSIONS: PI-9 mRNA levels in urinary cells are diagnostic of acute rejection,
      predict renal allograft histology grade, and predict functional outcome following
      an acute rejection episode.

PMID- 12792518
TI  - Chimerism and tolerance in rat recipients of intestinal allografts from ALS
      treated donors with and without adjunct naive-donor-strain bone-marrow cells.
AB  - BACKGROUND: BN --> LEW small-intestine transplantation (SITx) given a 28-day
      course of tacrolimus results in partial tolerance and prolonged alloengraftment
      despite the development of indolent chronic rejection (CR). We determined whether
      the CR was associated with the quantity or quality of passenger leukocytes
      contained in the unmodified or antilymphocyte serum (ALS)-depleted BN intestine
      at the time of transplantation, and with the subsequent migration and persistence
      of these donor leukocytes in the LEW recipients (chimerism). METHODS: Four
      experimental cohorts were defined by differences of the BN allografts and by the
      infusion (or not) of naive donor (bone marrow cells [BMC]) on the day of the BN -
      > LEW SITx. All LEW recipients were treated with the same 28-day course of
      tacrolimus. The LEW animals received: (1) unaltered intestine; (2) intestine from
      ALS-treated donor; (3) intestine from ALS-treated donor plus BMC from naive BN
      donor on day 0; and (4) unaltered intestine and BMC from unmodified (naive) BN
      donor. RESULTS: Blood chimerism during the first 2 weeks after transplantation
      was lowest in the recipients of intestine from ALS-treated donors (groups 2 and
      3), apparently because of the nearly complete elimination from the bowel of
      alphabetaTCR+ passenger leukocytes. After 2 weeks posttransplant to 5 months,
      greater than 2% of circulating donor cells were seen in animals given adjunct BMC
      from naive BN donors (groups 3 and 4); this was associated with the absence of CR
      in the intestinal allografts. With lower levels of chimerism, moderate CR
      including arteritis and fibrosis in the Peyer's patches and mesenteric lymph
      nodes was found in the intestinal grafts of all group 1 and group 2 animals.
      Nevertheless, the CR-prone recipients in groups 1 and 2 had equivalent weight
      gain for greater than or equal to 150 days as in the CR-free groups 3 and 4.
      Detailed tissue chimerism studies in groups 1 to 3 showed that most of the donor
      cells in the gut-associated lymphoid tissues were rapidly replaced, but that the
      residual donor constituency of up to 6% in the allografts of group 3 was nearly
      10-fold greater at 150 days than in groups 1 and 2 and closely reflected the
      findings in blood. CONCLUSION: The development of CR in intestinal allografts to
      which the recipients are partially tolerant is associated with a decline with
      time of donor-leukocyte chimerism. Multilineage chimerism in the recipient, and a
      similar profile of donor cells in the allografts, is better achieved with infused
      donor BMC than with the normal intestinal passenger leukocytes of the intestine.
      The difference may be because of a higher number of precursor and pluripotent
      stem cells in BMC.

PMID- 12792517
TI  - Nebulized amphotericin B concentration and distribution in the respiratory tract
      of lung-transplanted patients.
AB  - BACKGROUND: A criticism of using nebulized amphotericin B (nAB) as prophylaxis
      against Aspergillus infection after lung transplantation is the lack of knowledge
      of its pharmacokinetics and distribution in the lung. The aim of this study was
      to ascertain the concentrations and distribution of nAB in the respiratory tract
      of patients receiving lung transplantations. METHODS: In the drug-concentration
      study, 120 bronchoscopies were performed in 39 patients receiving lung
      transplantions after administration of 6 mg of nAB once daily for a minimum of 7
      days. Mean nAB concentration in bronchial aspirated secretions (BAS) and
      bronchoalveolar lavage (BAL) was determined at 4, 12, 24, and 48 hours
      postnebulization. In the distribution study, 17 patients inhaled 6 mg of 99m
      technetium-labeled AB, and pulmonary distribution was measured using a gamma
      camera. Pulmonary perfusion was also measured. Both tests were quantitatively
      evaluated. RESULTS: In the drug-concentration study, mean concentrations of 1.46
      microg/mL in BAS and 15.75 microg/mL in BAL were reached at 4 hours. At 24 hours,
      concentrations were 0.37 microg/m and 11.02 microg/mL in BAS and BAL,
      respectively. In the distribution study, 99m technetium-labeled AB distribution
      was uniform in 12 of 13 allografts without bronchiolitis obliterans syndrome
      (BOS) and in 1 of 4 allografts with BOS. A close correlation was observed between
      regional drug distribution and regional perfusion (r=0.82, P<0.01). CONCLUSIONS:
      nAB concentrations remained high for the first 24 hours in BAL and for less time
      in BAS, with distribution of the drug being uniform in patients without BOS.
      Furthermore, lung-perfusion studies appear to be useful to ascertain nAB
      distribution in patients receiving lung transplantions.

PMID- 12792519
TI  - Superior T-cell suppression by rapamycin and FK506 over rapamycin and
      cyclosporine A because of abrogated cytotoxic T-lymphocyte induction, impaired
      memory responses, and persistent apoptosis.
AB  - Immunosuppressive therapy is best achieved with a combination of agents targeting
      multiple activation steps of T cells. In transplantation, cyclosporine A (CsA) or
      tacrolimus (FK506) are successfully combined with rapamycin (Rap). Rap and CsA
      were first considered for combination therapy because FK506 and Rap target the
      same intracellular protein and thus may act in an antagonistic way. However, in
      clinical studies, FK506+Rap proved to be effective. To date, there is no in vitro
      data supporting these in vivo findings, and it is unclear whether the observed
      effects are T-cell mediated. In a human polyclonal allogeneic in vitro model, we
      found that although combined drug treatment markedly reduced expansion of naive T
      cells, T-cell activation occurred irrespective of the drug combination used. The
      induction of cytotoxic effector T cells was reduced by CsA+Rap but completely
      abolished by FK506+Rap. Importantly, combined immunosuppression allowed
      generation of memory CD4+ and CD8+ T cells and hence did not result in T-cell
      anergy. However, FK506+Rap treatment resulted in a reduced number of allospecific
      memory T cells showing a decreased cell-cycle turnover and cytokine producing
      capacity. In contrast, CsA+Rap treatment led to increased memory T-cell numbers
      responding with elevated kinetics. The ability of Rap to promote apoptosis, which
      contributes to T-cell suppression, remained unaffected upon combination with
      FK506 or CsA. These data support the combined use of FK506+Rap over CsA+Rap for
      immunosuppressive therapy.

PMID- 12792520
TI  - An extraperitoneal isolated vascularized bone marrow transplant model in the rat.
AB  - An isolated vascularized bone marrow transplant (iVBMT) model was previously
      developed in the rat to specifically study the role of bone marrow and its
      environment in a composite tissue allotransplant. An extraperitoneal model was
      successfully created to avoid laparotomy and cross-clamping of the great vessels.
      The extraperitoneal iVBMT model consisted of a left donor femur that was
      harvested with its nutrient vessels, anastomosed to the right femoral vessels in
      a syngeneic host, and then placed subcutaneously in the abdominal wall. At
      explant, the graft vessels were grossly patent, and histology of the graft bones
      showed a viable marrow compartment. Polymerase chain reaction demonstrated
      peripheral chimerism in the recipients. This model is technically simple with
      minimal morbidity in the recipient animals. By using the iVBMT, future studies
      across semiallogeneic and allogeneic barriers will help define the role of the
      bone marrow compartment in composite tissue allotransplants to potentially induce
      immune tolerance.

PMID- 12792521
TI  - Immunoprotection of rat islet xenografts by cotransplantation with sertoli cells
      and a single injection of antilymphocyte serum.
AB  - BACKGROUND: Islet transplantation has become a clinical reality; however, before
      it can be extended to young juvenile diabetics an unlimited supply of tissue is
      needed and the use of chronic immunosuppression should be eliminated. This study
      was designed to determine whether Sertoli cells can immunoprotect islet
      xenografts. METHODS: Lewis rat islets were cotransplanted with Balb/c Sertoli
      cells in diabetic Balb/c mice treated with one injection of anti-mouse lymphocyte
      serum (ALS). RESULTS: When islets were transplanted alone, in combination with
      Sertoli cells, or in combination with ALS, mean graft survival times were 10.9+/
      0.8, 14.0+/-1.2, or 12.2+/-0.7, respectively. When islets were combined with
      Sertoli cells and ALS, mean graft survival time increased to 64.9+/-8.1.
      CONCLUSIONS: Sertoli cells are able to prolong the survival of islet xenografts
      when combined with ALS, thereby supporting their use as a means to immunoprotect
      cellular grafts such as islets for the treatment of type 1 diabetes.

PMID- 12792522
TI  - Living-related liver transplantation with renoportal anastomosis for a patient
      with large spontaneous splenorenal collateral.
AB  - BACKGROUND: A large splenorenal collateral must be interrupted during liver
      transplantation to secure adequate portal perfusion. However, this process
      increases the complexity of the operative procedure and may cause hazardous
      bleeding. Recently, renoportal anastomosis in portal reconstruction was reported
      in cadaveric liver transplantation for patients with surgically created
      splenorenal shunts. We used this technique in a living-related liver
      transplantation. METHODS: A 29-year-old female with a large spontaneous
      splenorenal collateral and a portal venous thrombus underwent a living-related
      liver transplantation. At surgery, the left renal vein was divided and the distal
      stump was anastomosed to the portal vein of the graft without interrupting
      collaterals. RESULTS: Adequate portal venous blood flow was maintained throughout
      the postoperative course. The patient was discharged 9 weeks after
      transplantation and remains well. CONCLUSION: The renoportal anastomosis could be
      used for portal reconstruction in living-related liver transplantation for
      patients with a large splenorenal collateral. It provides adequate portal
      perfusion without interrupting collateral circulation.

PMID- 12792523
TI  - Significant role of middle hepatic vein in remnant liver regeneration of right
      lobe living donors.
AB  - For adult patients with end-stage liver disease, living-donor liver
      transplantation (LDLT) of right-lobe grafts with or without the middle hepatic
      vein (MHV) has been increasingly used in recent years. We investigated the role
      of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has
      not been described in previous studies. A total of eight living donors were
      included in this study of right-lobe LDLT. Four donors underwent right lobectomy
      (without MHV), and the remaining four underwent extended right lobectomy (with
      MHV). Regeneration of the donor remnant liver was assessed by volumetric computed
      tomography studies before and 90 days after LDLT. Comparison between the right
      lobe and extended right-lobe donors did not show a clear-cut difference in the
      net increase of remnant liver volume at 3 months. However, the mean volume
      increase of the medial segment at the 90th postoperative day was 7% in the
      extended right-lobe donors and 61% in the right-lobe donors, showing a lower
      value in the remnant livers without MHV. The MHV plays a specific role in remnant
      liver regeneration of right-lobe living donors. We expect that this knowledge
      will contribute to securing a margin of safety in right-lobe LDLT.

PMID- 12792524
TI  - Humoral immune reactivity against human leukocyte antigen (HLA)-DQ graft
      molecules in the early posttransplantation period.
AB  - Humoral graft-specific alloreactivity was investigated in 110 renal transplant
      (RTx) recipients (group A) starting immediately postTx and in 32 RTx candidates
      sensitized against a failed graft (group B) using an enzyme-linked immunosorbent
      assay (ELISA) assay. All patients received a human leukocyte antigen (HLA) class
      I and II incompatible graft. Donor-specific (DS) antibodies were detected in 11
      of 110 (90.9%) group-A patients, predominately during the first 6 months postTx.
      In all 11 cases, only HLA class II antibodies were detected. Ten of 11 antibody
      positive patients received an HLA-DR, HLA-DQ incompatible graft, and all patients
      had HLA-DQ DS antibodies, either alone (n=8) or with HLA-DR antibodies (n=2). HLA
      DQ antibodies were also detected in 80.9% of group-B patients. The presence of
      HLA-DQ DS antibodies in the early postTx period does not identify patients with
      rejection or deterioration of graft function. Whether these patients are at high
      risk for graft loss remains to be clarified.

PMID- 12792525
TI  - Dietary intervention after renal transplantation.

PMID- 12792526
TI  - Long-term consideration of hand transplantation.

PMID- 12792527
TI  - Successful adult ABO-incompatible liver transplantation: therapeutic strategy for
      thrombotic microangiopathy is the key to success.

PMID- 12792528
TI  - Functional tolerance following face transplantation in the rat.

PMID- 12792529
TI  - Case 4: cardiovascular risk in renal transplantation.

PMID- 12792530
TI  - Fate of exposed breast implants in augmentation mammoplasty.
AB  - Exposure of silicone breast implants usually leads to infection and extrusion.
      According to the literature, implant extrusion rates are not higher than 2% 1 and
      removal of the implant is recommended. 2 During the past 3 years, the authors
      dealt with eight implant exposures (six women: two cases of bilateral exposure
      and four cases of unilateral exposure). All the pockets were infected. Patients
      were offered two alternatives: immediate removal of the implant and
      reimplantation after a few months or conservative treatment with an effort to
      close the exposed area after the discharge stopped. All the patients in this
      study chose the latter alternative. Four out of eight implants were saved. The
      authors had to remove the other four. The average follow-up of these women was 2
      years and there were no signs of capsular contracture or any other problems.
      According to this series, 50% of eight exposed breast implants could be saved
      with conservative treatment.

PMID- 12792531
TI  - Swallowing function in patients who underwent hemiglossectomy: comparison of
      primary closure and free radial forearm flap reconstruction with
      videofluoroscopy.
AB  - The swallowing function of patients who had undergone hemiglossectomy with either
      primary closure of the defect or radial forearm flap reconstruction was studied
      with videofluoroscopy. Patients with primary closure were unable to lift the
      tongue tip, had poor tongue-to-palate contact on initiating swallowing, had
      premature spilling of the bolus into the pharynx, had a large amount of barium
      stasis on the floor of the mouth, and had prolonged oral transit time. With flap
      reconstruction, patients easily could lift the tongue and make good contact with
      the entire palate. They were able to seal the posterior pharyngeal sphincter by
      elevation of the reconstructed tongue, approximating it to the soft palate, so
      that premature spilling of the bolus rarely happened. Their swallowing pattern
      was nearly normal. Although the reconstructed flap is nonfunctional, it provides
      bulk and helps the remaining tongue to complete the swallow. Compared with
      primary closure of the tongue defect, the authors suggest it is better to
      reconstruct it with a free radial forearm flap when more than 50% of the tongue
      is resected.

PMID- 12792534
TI  - Upper blepharoplasty with lateral segmental orbicularis excision.
AB  - In an effort to avoid symptoms of persistent lateral eyelid excess, exaggerated
      segmental resection of lateral preseptal orbicularis oculi muscle is performed.
      This involves an elliptical excision of the lateral orbicularis oculi muscle
      larger than that traditionally described using the blepharoplasty incision. This
      results in a relative advantage to the frontalis muscle, limiting the descent of
      the lateral brow soft tissues. The procedure was performed on 59 patients over a
      period of 1 year. None of these patients reported persistent lateral excess after
      surgery.

PMID- 12792532
TI  - Surgical management of the hand in Freeman-Sheldon syndrome.
AB  - Freeman-Sheldon syndrome is a rare form of distal arthrogryposis characterized by
      craniofacial anomalies, a rheumatoid-appearing hand, and pedal deformities. The
      hand deformities include ulnar deviation of the fingers, camptodactyly, first web
      space contracture, and hypoplasia of the thumb. Because of clinical variability
      and rarity, there is no standard management protocol. The authors have developed
      a systematic method of management of the hand in Freeman-Sheldon syndrome using
      principles commonly applied to other complex hand problems. In 17 years, the
      authors have evaluated nine patients. Of 18 hands evaluated, the authors have
      operated on 15. Good results were achieved in five hands and fair results in 10.
      There were no cases of useless hands. The authors have been most pleased with the
      results after crossed intrinsic transfers, centralization of extensor tendons,
      and intrinsic release of the thumb. Although physical deformities remain,
      functional adaptation is generally good.

PMID- 12792535
TI  - Skin expansion before breast reconstruction with the superior gluteal artery
      perforator flap improves aesthetic outcome.
AB  - To improve the aesthetic outcome in the reconstructed breast and in the flap
      donor area, the technique of skin expansion in the mastectomy site was used in
      eight patients who subsequently underwent breast reconstruction using the
      superior gluteal artery perforator (SGAP) flap. The authors think that skin
      expansion before final reconstructive surgery provides adequate ptosis and better
      positioning of the flap on the chest, leading to a more natural appearance and
      symmetry of the reconstructed breast. Furthermore, the skin expansion reduces the
      amount of free flap skin required for breast reconstruction, resulting in less
      donor site scarring and morbidity. They present their surgical refinements to
      improve the aesthetic appearance of the breast reconstructed using the SGAP flap.

PMID- 12792536
TI  - Hemiphiltrum rotated flap.
AB  - In three patients of different ages, large resections of the philtrum have been
      repaired by rotating island flaps from the residual philtrum, leaving
      inconspicuous scars and no contour deformity. The rotated hemiphiltrum flap
      described here is an easy and safe procedure performed with local anesthesia that
      may be an effective cosmetic and functional repair of selected difficult surgical
      defects of the central upper lip involving the philtrum.

PMID- 12792537
TI  - Coverage of difficult wounds around the knee joint with prefabricated, distally
      based sartorius muscle flaps.
AB  - The coverage of soft-tissue defects around the knee joint presents a difficult
      challenge to the reconstructive surgeon. Various reconstructive choices are
      available depending on the location, size, and depth of the defect relative to
      the knee joint. However, the knee joint frequently accompanies injuries to the
      lower leg that may limit the use of muscle flaps, especially the gastrocnemius
      muscle. The use of a free flap is preferred for reconstruction involving
      obliteration of large-cavity defects, but the isolation of recipient pedicle can
      be difficult because of the extent of injury zone and in cases of chronic
      infection around the knee. To provide muscle bulk with a reliable vascular
      supply, the distally based, prefabricated sartorius muscle flap was used as a
      last resort to reconstruct difficult wounds with chronic osteomyelitis around the
      knee joint in 6 patients from June 1995 to May 2001. This method is a two-stage
      procedure. First, the sartorius muscle is prefabricated by denervation and
      vascular delay. Silicone sheets are used to increase the vascularity and
      dimension of the flap. Second, after 3 weeks, the muscle is transposed based on a
      distal pedicle to reconstruct the soft-tissue defect around the knee. The
      prefabricated sartorius muscle can provide efficient bulk to obliterate the dead
      space and to cover moderate-size soft-tissue defects around the knee joint. This
      method can be considered to reconstruct the soft tissue around the knee joint
      when local muscle flaps and free flaps are not feasible.

PMID- 12792538
TI  - Local perforator flap for reconstruction of deep tissue defects in the elbow
      area.
AB  - Limited deep tissue defects in the elbow area can occur after burns, advanced
      bursitis, and inflammatory processes, to name a few. Reconstruction is
      complicated because sufficient tissue with adequate elasticity and strength has
      to be transferred. Often major surgical procedures such as free tissue transfer
      are considered. A novel method for reconstruction of deep tissue defects in the
      elbow area, based on a single perforator artery and vein, is described.
      Perforator vessels are identified preoperatively using color Doppler
      ultrasonography, and a flap from the upper arm is rotated 180 degrees. The
      authors describe the successful treatment of two patients. The surgical technique
      is comparatively simple and can be performed with regional anesthesia.
      Postoperative recovery is short and skin sensibility is retained. The authors
      suggest that local, single perforator flaps can be considered as a first
      alternative in treatment of limited, deep tissue defects in the elbow area,
      especially for elderly or severely ill patients.

PMID- 12792539
TI  - Various applications of the medial plantar flap to cover the defects of the
      plantar foot, posterior heel, and ankle.
AB  - The medial plantar fasciocutaneous flap provides structurally similar tissue to
      plantar foot, posterior heel, and ankle defects with its thick glabrous plantar
      skin, shock-absorbing fibrofatty subcutaneous tissue, and plantar fascia. During
      the past 4 years, 24 patients (20 men, 4 women) with skin and soft-tissue defects
      over the plantar foot, posterior heel, or ankle were treated. They ranged in age
      from 20 to 42 years (mean, 24 y). The medial plantar flap was transposed to the
      defects in four different ways: proximally pedicled sensorial island flaps (N =
      18), reverse-flow island flaps (N = 2), free flaps (N = 2), and cross-foot flaps
      (N = 2). Flap size varied from a width of 2 to 5.5 cm and a length of 5 to 7.5
      cm. The follow-up period ranged from 2 to 18 months (mean, 9 mo). Partial flap
      loss was observed in one free flap and one reverse-flow island flap. Partial skin
      graft lost in the donor site required regrafting in one patient. Durable, sensate
      coverage of the defects was achieved in all patients.

PMID- 12792540
TI  - Long-term fate of vascularized iliac bone flap as a source for phallic rigidity.
AB  - One of the surgical goals of phalloplasty is to obtain sufficient rigidity for
      sexual penetration. This is also important for patients with erectile
      dysfunction. Different kinds of techniques have described phalloplasty and
      obtaining rigidity in patients with erectile dysfunction, but there is no good
      substitute for the erectile tissue of the penis. The authors used an iliac
      osteocutaneous flap for phalloplasty and a vascularized bone flap for imitating
      penile erection. Five patients who had undergone either phalloplasty or
      correction of erectile dysfunction are presented. Long-term results are promising
      in adults and the authors advocate using vascularized iliac bone for sufficient
      rigidity of a (neo)phallus. However, the results are moderate for children who
      have undergone previous phalloplasty.

PMID- 12792541
TI  - Breast-areola-nipple proportion.
AB  - Studies of breast volume and size have failed to take into account the aesthetic
      value of the nipple-areola-breast proportion. These data are important to plastic
      surgeons in planning breast reduction, augmentation, and reconstruction. In the
      current study, the anatomic size of the nipple, areola, and breast was measured
      in 37 women aged 20 to 64 years, and their proportions were calculated. The
      areola-breast and nipple-areola proportions were 1:3.4 and 1:3, respectively. The
      natural nipple-areola-breast proportion is approximately 1:3. This study provides
      a general guideline for plastic surgeons for planning breast surgery with optimal
      aesthetic results.

PMID- 12792542
TI  - Vertical (two-layer) skin grafting: new reserves for autologic skin.
AB  - The main, permanent source of burn coverage continues to be autologic skin. In
      patients with major burns, the amount of available autologic skin may be
      insufficient. Consequently, severe wounds are covered after debridement with
      other biological or synthetic skin substitutes. Another source of skin reserves
      for wound coverage is the use of cultured keratinocyte sheet graft alone or with
      any dermal substitute. Some of these materials provide only temporal coverage and
      are often costly and time-consuming in preparation. These factors can be critical
      in burned patients. To expand the effective means of wound coverage, the authors
      sought a new source of autologic skin. The dermal grafts that were the marginal
      product of skin harvesting were meshed and grafted on the debrided third-degree
      burn, granulated wound, or muscle. The authors observed good dermal grafts "take"
      with rapid or slow epithelialization. They saw no the delay in donor site healing
      where the skin grafts overlapped. The histological difference in usual skin
      grafts and dermal grafts was studied after their harvesting and "taking."

PMID- 12792543
TI  - Innervation of calf muscles in relation to calf reduction.
AB  - Plump and muscular calves, a so-called radish-like leg, embarrass young women and
      cause a feeling of inferiority in Korea. Damage to motor nerves innervating a
      muscle makes the muscle paralyzed and dystrophic, with loss of muscle volume. The
      authors studied the morphometry of the motor branches of the tibial nerve
      innervating the gastrocnemius and soleus muscle and sensory medial sural
      cutaneous nerve in popliteal fossa. Dissection and exploration of the tibial
      nerve were performed in the popliteal fossae of 70 legs (of 18 males and 17
      females) of embalmed Korean cadavers. The main branch of the tibial nerve
      innervating medial and lateral gastrocnemius muscle originated 3 cm above and
      below the popliteal crease. The medial gastrocnemius muscle had an additional
      nerve (49%). The medial sural cutaneous nerve came off the nerve into the medial
      gastrocnemius muscle (30%) and diverged 5.5 mm from the tibial nerve. The nerve
      into the soleus muscle originated from the nerve innervating the lateral
      gastrocnemius muscle (30%) and was 12.3 mm away from it. Surgeons should keep in
      mind that the medial sural cutaneous nerve originates from the nerve to medial
      gastrocnemius in 30% and the nerve to soleus muscle originates from the nerve to
      lateral gastrocnemius in 30%.

PMID- 12792544
TI  - Revascularization of human acellular dermis in full-thickness abdominal wall
      reconstruction in the rabbit model.
AB  - This study investigates whether human acellular dermis (Alloderm; LifeCell,
      Branchburg, NJ) revascularizes when used to reconstruct abdominal wall defects in
      rabbits. This could prove useful in infected situations in which prosthetic mesh
      is suboptimal. Twenty-five rabbits were randomly assigned to one of three groups:
      primary closure (n = 5), expanded polytetrafluoroethylene (GoreTex; W.L. Gore,
      Flagstaff, AZ) repair (n = 10), or AlloDerm (LifeCell) repair (n = 10). The
      rabbits in the primary closure group received a 7 cm x 0.5 cm full-thickness
      abdominal wall defect that was closed primarily. A 7 cm x 3 cm full-thickness
      abdominal wall defect was created in the other two groups. The defects were
      repaired with a GoreTex Mycromesh (W.L. Gore), or AlloDerm (LifeCell) patch. At
      30 days, the following endpoints were evaluated: (1) incidence of herniation; (2)
      presence of intra-abdominal adhesions; (3) the breaking strength of the patch
      fascial interface; and (4) evaluation of graft vascularization by fluorescein dye
      infusion and histological analysis. There was no incidence of herniation in any
      of the rabbits. Visceral adhesions to the patch were found in all animals in the
      Gore-Tex (W.L. Gore) group but in none in the AlloDerm (LifeCell) group. The size
      of the patch was unchanged in all the rabbits except for two rabbits in the
      AlloDerm (LifeCell) group that stretched 1 cm in the transverse dimension. The
      change in size was not statistically significant (p = 0.17) when compared with
      the change in size in the Gore-Tex (W.L. Gore) group. The mean breaking strength
      of the primary closure group was significantly higher (521.2 N/mm2 +/- 223.0)
      than that of the two patch-repair groups (p < 0.05). But there was no significant
      difference between the mean breaking strength of the AlloDerm (LifeCell) fascial
      interface (288.6 N/mm2 +/- 97.1 SD) and that of the Gore-Tex (W.L. Gore) fascial
      interface (337.0 N/mm2 +/- 141.2). Fluorescein dye infusion and histological
      analysis confirmed vascularization of the AlloDerm (LifeCell) graft. This study
      demonstrates that AlloDerm (LifeCell) does become vascularized when used as a
      fascial interposition graft for abdominal wall reconstruction. AlloDerm
      (LifeCell) also performs mechanically as effectively as Gore-Tex (W.L. Gore) in
      ventral hernia repair at 1 month after operation in the rabbit model.

PMID- 12792545
TI  - Effect of lyophilized heterologous collagen on new cartilage formation from
      perichondrial flaps in rabbits: an experimental study.
AB  - New cartilage formation originated from perichondrium has previously been
      researched in many clinical and experimental studies. 1-6 After these studies,
      the use of perichondrium for the repair of cartilage defects has been used
      clinically when enhancing neochondrogenesis has been found to be of great value
      in decreasing the recovery period. Collagen is the major protein of whole
      connective tissue, and in vitro positive effects of collagen matrices on
      neochondrogenesis have also been studied before. 7-9 In this experimental study,
      in vivo effects of heterologous collagen sponge in perichondrial
      neochondrogenesis were examined in an animal model, and acceleration and
      enhancement effects were observed.

PMID- 12792546
TI  - First successful replantation of face and scalp with single-artery repair: model
      for face and scalp transplantation.
AB  - Successful replantation of the scalp with microanastomosis of a single artery and
      vein has been reported to produce reliable results. In fact, there have been
      several reports of scalp replantations based on one-artery and vein repair. There
      has been a face and scalp replantation reported in the literature, but this was
      as two separate parts and was based on several arterial and venous repairs. The
      authors performed the first successful replantation of a face and scalp with
      repair of a single artery and, of course, two veins. A 21-year-old man presented
      after his face and scalp were completely severed. The patient's long hair was
      caught in a conveyor belt at work. The face and scalp underwent replantation,
      with repair of the right superficial temporal artery with an interposition vein
      graft. A multiteam approach allowed for minimization of overall ischemic time and
      simultaneous preparation of the vessels on the patient and amputated part as well
      as vein graft harvest from the arm. Also critical to the success of the
      procedure, the small portions of the vessels of the amputated part were sent for
      frozen section to differentiate artery from vein. Initially, only the right
      superficial temporal vein was repaired. One week after replantation, the patient
      returned for treatment of venous congestion of an area to the opposite side of
      the forehead partial transection, with repair of the left superficial temporal
      vein, also. This saved the entire part that underwent replantation, and the
      entire part survived. The face and scalp can undergo replantation based on single
      artery repair.

PMID- 12792547
TI  - Ball lightning burn.
AB  - Ball lightning is a rare physical phenomenon, which is not yet completely
      explained. It is similar to lightning but with different, peculiar
      characteristics. It can be considered a mix of fire and electricity, concentrated
      in a fireball with a diameter of 20-cm that most commonly appears suddenly, even
      in indoor conditions, during a thunderstorm. It moves quickly for several meters,
      can change direction, and ultimately disappears. During a great storm, a 28-year
      old man and his 5-year-old daughter sustained burn wounds after ball lightning
      came from the outdoors through a chimney. These two patients demonstrated signs
      of fire and electrical injuries. The father, who lost consciousness, sustained
      superficial second-degree burn wounds bilaterally on the zygomatic area and deep
      second-degree burn wounds on his right hand (total body surface area, 4%). His
      daughter demonstrated superficial second-degree burn wounds on the left part of
      the face and deep second-degree and third-degree burn wounds (total body surface
      area, 30%) on the left neck, both upper arms, and the back. In this article, the
      authors report the first two cases of burn injuries resulting from ball lightning
      contact indoors. The literature on this rare phenomenon is reviewed to elucidate
      the nature of ball lightning. Emphasis is placed on the nature of injuries after
      ball lightning contact, the therapy used, and the long-term complications.

PMID- 12792548
TI  - Glans, urethra, and corporeal body reconstruction by free osteocutaneous forearm
      flap transfer.
AB  - A 30-year-old man presented with short penile corporeal bodies hosting a 3-cm
      fibular graft, absence of glans, and proximal penile hypospadias. The patient
      underwent a forearm flap transfer with an "umbrella-like" skin flap for glans and
      urethra reconstruction and a radial bone strut to allow for rigidity. The
      postoperative course was uneventful and the patient was followed-up with
      fluximetry tests at 2 weeks, 4 weeks, 2 months, and 6 months, showing no stenoses
      and normal stable values. Masturbation started at month 3 postoperatively and
      intercourse began at month 4, with both resulting in orgasm. At 6 months
      postoperatively, touch sensation, pain, and sensibility to heat were present, but
      sensibility to cold was absent. Light touch pressure was detected with 4.74
      Semmes-Weinstein monofilament, and static two-point discrimination was 20 mm at
      the neoglans. One year postoperatively, a stable increased length up to 9 cm at
      rest and 13 cm at erection with a satisfactory anatomic definition could still be
      proved.

PMID- 12792549
TI  - Cleft palate with congenital midline teratoma.
AB  - A 4-year-old girl presented with hypernasal speech. On examination, in addition
      to velopharyngeal incompetence noted by speech examination, a palatal tumor was
      found in between the cleft palate. The computed tomographic and magnetic
      resonance imaging examinations were suspicious for midline teratoma. Total
      excision of the nasopalatal tumor was performed, and the pathology revealed
      benign teratoma. After 6 months of follow-up, no recurrence was noted. A two-flap
      palatoplasty with a superior-based pharyngeal flap was then performed to
      reconstruct the palatal defect and to correct the velopharyngeal incompetence. An
      anterior oronasal fistula developed after the operation, but a tongue flap was
      transferred to cover the defect successfully. The purpose of this case report is
      to present the relationship between a congenital midline nasopalatal tumor and
      cleft palate.

PMID- 12792550
TI  - Nodal metastatic melanoma in the neck of a 4-year-old girl after diagnosis of
      Spitz nevus of the cheek.
AB  - A 4-year-old girl was referred to the plastic surgery unit with metastatic
      malignant melanoma diagnosed in a cervical lymph node. She had previously
      undergone excision of a Spitz nevus of the cheek at age 18 months. The management
      of this patient is discussed along with a review of the literature relating to
      Spitz nevi and malignant melanoma in childhood.

PMID- 12792552
TI  - NIH-FDA Analgesic Drug Development Workshop: translating scientific advances into
      improved pain relief.
AB  - Analgesic drug development as currently undertaken is limited by a number of
      factors that contribute to the paucity of new analgesics introduced into clinical
      practice despite marked advances in delineating of the molecular-genetic
      mechanisms contributing to acute and chronic pain. The participants in this
      workshop explored the unmet need in analgesia and recommended strategies for
      enhancing analgesic drug development in the future. The workshop concluded that
      translating scientific advances into improved pain relief will require new
      thinking and a cooperative effort among the pharmaceutical industry, regulatory
      agencies, funding agencies, the biomedical research community, professional
      societies and clinicians. The workshop also recommended that a better
      understanding of the epidemiology of pain could contribute to improvement in
      clinical trial methodology and outcome measures.

PMID- 12792553
TI  - Treatment of pain in pregnancy.
AB  - BACKGROUND: The treatment of pain during pregnancy other than that of labor is a
      clinical issue that has not been addressed in a systematic manner. MATERIALS AND
      METHODS: To assess current knowledge, a review of the human and animal
      literatures was undertaken using MEDLINE. In addition, the dynamics of three
      pharmacological compartments, the mother, the placenta, and the fetus, and fate
      of drugs given in pregnancy, was reviewed. RESULTS: The literature review yielded
      little information except for a few case studies in which opiates, nonsteroidal
      anti-inflammatory drugs, antidepressants, mu agonists, and anticonvulsants were
      used in the treatment of pain in pregnancy. In contrast, there is extensive
      information in the addiction medicine literature concerning the use of opioids in
      recovering pregnant addicts. Methadone, buprenorphine, and morphine have been
      used to treat women seeking recovery from opioids, and neonatal outcomes have
      been closely monitored with no evidence of harm to the newborn. CONCLUSIONS:
      Experience in women seeking recovery from opioids and their newborns illustrates
      that opioids are an effective and safe pharmacological option for the treatment
      of pain during pregnancy. Controlled studies are needed to expand knowledge in
      this clinical area.

PMID- 12792554
TI  - Efficacy of a self-management group intervention for elderly persons with chronic
      pain.
AB  - OBJECTIVES: To assess the efficacy of a self-management group intervention in
      improving physical functioning, mood, and pain among elderly persons with chronic
      pain, and to identify factors that may be associated with improvement. MATERIALS
      AND METHODS: Forty-five residents of three retirement communities (86% women;
      mean age, 82.0 years) were assigned randomly to a 7-week pain self-management
      group or an educational booklet control condition. Participants completed self
      report measures of pain, functioning, depression, and pain-related beliefs at
      baseline, 9 weeks later (after treatment), and 3 months after the post-treatment
      assessment. RESULTS: The self-management group showed significantly greater pre-
      to post-treatment improvement in physical role function (P = 0.04) and
      characteristic pain intensity (P = 0.02). No significant differences were found
      between groups on measures of pain-related activity interference, depression, and
      pain-related beliefs. Improvement in characteristic pain and physical role
      function was not associated with baseline depression scores, pretreatment
      expectations, or changes in pain-related beliefs. DISCUSSION: This study provides
      preliminary support for the efficacy of a self-management group intervention for
      older adults with chronic pain and has implications for future studies of such
      approaches for this and similar populations.

PMID- 12792555
TI  - Gonadal hormones and sex differences in pain reactivity.
AB  - BACKGROUND: Sex differences in the response threshold to painful stimuli and the
      higher number of chronic pain syndromes in women than in men have prompted a
      series of studies on lower animals and humans aimed at clarifying the role of
      gonadal hormones in pain. OBJECTIVE: This article examines the morphologic and
      functional aspects of gonadal hormone systems and the relations between gonadal
      hormones and pain circuits, to identify areas deserving of increased attention in
      elucidating the endocrine mechanisms that contribute to abnormal pain states.

PMID- 12792556
TI  - Sex differences in opioid analgesia: "from mouse to man".
AB  - BACKGROUND: Numerous experimental studies, conducted primarily over the past 10
      years, show that there are sex differences in opioid analgesia. This review
      summarizes the published literature on sex differences in analgesia produced by
      acute administration of drugs acting at mu-, kappa-, and delta-opioid receptors,
      in animals and humans. Additionally, methodological issues in research into
      opioid sex differences are discussed. CONCLUSIONS: Procedural variables that may
      influence the outcome of studies examining sex differences in opioid analgesia
      include modality and intensity of the noxious stimulus used in the pain test,
      opioid type (efficacy and selectivity), and experimental design and data analytic
      techniques. Subject variables that may be important to consider include subject
      genotype and gonadal steroid hormone state of the subject at the time of
      analgesia testing. Evidence is provided for multiple mechanisms underlying sex
      differences in opioid analgesia, including both pharmacokinetic and
      pharmacodynamic factors. Future research directions are suggested, such as
      examining sex differences in opioid tolerance development, sex differences in
      opioid analgesia using models of acute inflammatory pain and chronic pain, and
      sex differences in effects of opioids other than analgesia, which may limit their
      therapeutic use.

PMID- 12792557
TI  - Acupuncture during labor can reduce the use of meperidine: a controlled clinical
      study.
AB  - OBJECTIVE: To evaluate the effectiveness of acupuncture as an analgesic during
      labor. DESIGN: A randomized, unblinded, controlled study. SETTING: A labor ward
      in a University Hospital. PATIENTS: Parturients at term. INTERVENTIONS: One group
      received acupuncture (N = 106); another did not (N = 92). A second control group
      (N = 92), drawn from the labor ward protocol, consisted of patients who met the
      eligibility criteria for the study and were matched to the "no acupuncture" group
      by parity, but who had not been offered the opportunity to take part. Outcome
      measure "effectiveness of acupuncture" was measured by the requirement for use of
      meperidine. RESULTS: Meperidine was given to 11% of the acupuncture group, 37% of
      the no acupuncture group (P < 0.0001), and 29% of the control group. The use of
      other analgesics was also lower in the acupuncture group. Patient satisfaction
      was high: 89 of 103 patients asked said they would want acupuncture during
      another labor. CONCLUSIONS: Acupuncture during labor reduced the requirement for
      other painkillers and has high patient satisfaction in this randomized,
      unblinded, controlled study.

PMID- 12792559
TI  - The cholecystokinin antagonist proglumide enhances the analgesic effect of
      dihydrocodeine.
AB  - AIM: To investigate the potential pro-analgesic effect of the non-specific CCK
      antagonist proglumide on the analgesia produced by dihydrocodeine. METHOD: A
      double-blind, placebo-controlled crossover study of 30 adult subjects. RESULTS:
      Mean pain scores fell from a baseline of 8.12-7.89 during the placebo phase
      (N.S.) and to 6.82 during the proglumide phase (P < 0.05). Side effects were
      minor. CONCLUSION: The CCK antagonist proglumide enhances the analgesic effect of
      dihydrocodeine.

PMID- 12792558
TI  - Characteristics and associated features of persistent post-sympathectomy pain.
AB  - OBJECTIVES: The aim of this study is to describe the incidence and
      characteristics of pain, sensory abnormalities, abnormal body sweating, and
      pathologic gustatory sweating in pain patients with persistent post-sympathectomy
      pain. METHODS: A retrospective chart review of a series of consecutive pain
      patients with persistent post-sympathectomy pain was performed. Inclusion
      criteria were: (1) sympathectomy performed for the indication of neuropathic
      pain, and (2) persistent pain after the procedure. Demographic data, patterns of
      pain before and after sympathectomy, patients' pain drawings, and incidence of
      pain had been collected concurrently at the time of referral. Additional data
      regarding sensory findings, surgical details of the sympathectomy, sweat
      patterns, and incidence of abnormal body sweating and pathologic gustatory
      sweating were extracted from the patients' charts or obtained in follow-up
      appointments. RESULTS: Seventeen adults (13 females and 4 males) with a mean age
      of 37 years (range 25-52) at the time of sympathectomy met the inclusion
      criteria. Five of the 17 patients experienced temporary pain relief for an
      average of 4 months (range 2-12 months), 3/17 retained the same pain as before
      the surgery, 1 patient was cured of her original pain but experienced a new
      debilitating pain, and 8/17 patients continued to have the same or worse pain in
      addition to a new or expanded pain. Pathologic gustatory sweating was present in
      7/11 patients asked, and abnormal sweating (known as compensatory hyperhidrosis)
      in 11/13 patients asked. DISCUSSION: The present study does not allow for
      conclusions about the effectiveness of surgical sympathectomy for neuropathic
      pain. However, our findings indicate that if the pain persists after the
      procedure, the complications may be quite serious and at times worse than the
      problem for which the surgery was originally performed.

PMID- 12792561
TI  - Patching up pain.

PMID- 12792562
TI  - Revisiting off-pump coronary revascularization.

PMID- 12792563
TI  - Strategies for treating migraine.

PMID- 12792565
TI  - Finding a way to avoid restraints.

PMID- 12792564
TI  - An interview with AACN President Connie Barden.

PMID- 12792567
TI  - What a gang member taught me about nursing.

PMID- 12792566
TI  - Nutrition series Managing nutrition in an acutely ill patient.

PMID- 12792568
TI  - Recognizing and managing deep vein thrombosis.

PMID- 12792569
TI  - Maple leaf madness.

PMID- 12792570
TI  - Benign prostatic hyperplasia.

PMID- 12792572
TI  - Picturing reciprocal changes in an MI.

PMID- 12792571
TI  - Chronic bronchitis and emphysema: clearing the air.

PMID- 12792573
TI  - Assessing the abdomen.

PMID- 12792574
TI  - Before & after.

PMID- 12792575
TI  - How to combat 3 deadly trauma complications.

PMID- 12792577
TI  - [Relationshipsbetween physicians and patients. How to adapt the charter of
      Medical Professionalism of the anesthesiologists].

PMID- 12792576
TI  - Narrow-complex tachycardia.

PMID- 12792578
TI  - Timing of operations in septic patients.

PMID- 12792579
TI  - SIAARTI guidelines for admission to and discharge from Intensive Care Units and
      for limitation of treatment in intensive care.

PMID- 12792580
TI  - Remifentanil for intraoperative analgesia during the endoscopic surgical
      treatment of pituitary lesions.
AB  - AIM: The authors have evaluated remifentanil for intraoperative analgesia in
      endonasal endoscopic surgery for pituitary lesions. METHODS:  EXPERIMENTAL
      DESIGN: a perspective, randomized and comparative study between remifentanil and
      fentanyl for intraoperative analgesia was performed in an operating room of the
      neurosurgical department at University. Sixty patients of both sexes were studied
      and randomly divided into 2 groups. Patients were premedicated with fentanyl 0.15
      microg.kg(-1) and atropine 0.01 microg.kg(-1) (group F) or with atro-pine and
      remifentanil 0.25 microg.kg(-1) min-1 (group R); induction was with propofol 2.0
      microg.kg(-1) and maintenance with titrated infusion of propofol and for
      intraoperative analgesia, fentanyl as bolus injection of 1.0-1.5 microg.kg(-1)
      (group F) or a titrated infusion of remifentanil (group R). The following
      parameters were studied: MAP, HR, bleeding, awakening times, adverse effects and
      VAS. RESULTS: Much more stable hemodynamic parameters during surgery in patients
      treated with remifentanil; labetalol was administered in 10% of patients in group
      F; no significant differences as regards the adverse effects and VAS. Faster
      awakening time was obtained in the remifentanil group as compared with the
      fentanyl group. CONCLUSIONS: Remifentanil analgesia (mean dose of 0.37 microg.kg(
      1).min-1) in patients undergoing endonasal endoscopic surgery of the sellar
      region provides a more efficacious cardiocirculatory control with reduced
      bleeding and faster psychosensorial recovery.

PMID- 12792581
TI  - Small doses of remifentanil and alfetanil in continuous total intravenous
      anesthesia in major abdominal surgery. A double blind comparison.
AB  - AIM: The purpose of this study was to test the safety and efficacy of small doses
      of remifentanil and alfentanil in a continuous total intravenous anesthesia
      technique for patients undergoing major abdominal surgery. METHODS: Sixty
      patients were enrolled in the study, and received in a double blind fashion
      either remifentanil (0.1 microg/kg/min) or alfentanil (alfentanil 0.75
      microg/kg/min) in association with propofol (12 mg/kg/h at induction; 6-9 mg/kg/h
      for maintenance) and cisatracurium. Hemodynamic data, hypnosis monitoring data
      (Bispectral Index Score), ventilatory parameters and settings, drug utilisation
      were monitored during stress moments and during all the intraoperative period.
      Patients were evaluated also in the first 6 postoperative hours. RESULTS: Mean
      amount of propofol for induction (BIS<60) was lower in the remifentanil group
      than in the alfentanil group. Significantly fewer patients receiving remifentanil
      responded to intubation in comparison with patients receiving alfentanil in terms
      of non invasive blood pressure (>30 mmHg) and heart rate variations.
      Significantly more patients receiving alfentanil had 1 or more responses to
      surgery. Incidence of hypotension was significantly higher in patients receiving
      remifentanil. There were no differences between the 2 groups in the times for
      spontaneous respiration, adequate respiration, adequate responsivness (OAA/s=5)
      and discharge from the recovery room. Time to extubation resulted slightly
      shorter (p<0.05) in patients who received remifentanil. CONCLUSIONS: The use of
      remifentanil and alfentanil in association with propofol, in a continuous
      infusion total intravenous anesthesia technique, demonstrated to be safe and
      reliable strategies.

PMID- 12792583
TI  - High-dose fluconazole therapy in Intensive Care Unit.
AB  - AIM: Fungal infections have become one of the emerging complications in intensive
      care patients and the morbidity and mortality linked to these infections
      underlines the importance of managing these pathologies. METHODS: The clinical
      and laboratory difficulties of diagnosing candidiasis prompted us to identify
      patients at risk and to intervene as soon as possible, where there was the
      "suspicion" of active infection, using adequate, so-called "empiric" treatment.
      The major risk factors include the use of invasive devices (central venous
      catheters), the administration of multiple antibiotic treatment and parenteral
      nutrition. In our Intensive Care ward (multi-purpose), we examined 1933 patients
      who had undergoing 1211 urine cultures (following consolidated clinical
      criteria). "Empiric treatment" was used in 378 high-risk patients with unstable
      clinical symptoms and positive urinary fungal colonisations using high-dose
      fluconazole (800 mg/die) according to the guidelines set down by BSAC. The mean
      duration of treatment was 12+2 days and urine cultures became negative in all
      patients after 1 or 2 weeks of treatment. RESULTS: We observed that fluconazole
      was generally well tolerated: only 10% of patients presented augmented hepatic
      transaminase. This phenomenon was always transient. Renal function remained
      unchanged (creatinine clearance). A severe infection with hematogenous
      dissemination was reported in 6 cases: "empiric treatment" was used in 5 cases
      with 800 mg/die of fluconazole and 1 case received amphotericin B 1 mg/kg/die
      (because no clinical improvement was observed after 48-72 hours of fluconazole
      treatment). Three of these 6 cases died, 2 of which were not directly linked to
      fungal infection, and 3 patient were discharged from the ward. CONCLUSIONS: We
      found that fluconazole offers a treatment option that is less toxic, less
      expensive and equally effective for these infections, provided that it is used at
      an adequate dose and that high-risk patients are identified for "empiric
      treatment". No significant increases in resistance were noted, as is demonstrated
      by the fact that only 1 case of candidemia required conversion to amphotericin B.

PMID- 12792582
TI  - One-stop surgery in pediatric surgery. Aspects of anesthesia. Preliminary report.
AB  - AIM: One-Stop Surgery (OSS) is a new day surgery combining preoperative
      evaluation and subsequent operation in one medical examination. METHODS: This
      paper reports the authors' initial experience using this method. Referring
      physicians were informed of the methods and selected surgical and anesthetic
      procedures by fax. They were also faxed a form to fill in with case history
      details and instructions to the parents on the preoperative fast. The completed
      form was faxed back to the surgeon and pediatric anesthetist who determined
      patient suitability and scheduled hospitalization and surgery. On hospitalization
      physical examination was performed to confirm diagnosis and rule out
      contraindications for anesthesia. Patients considered suitable then underwent
      surgery and were discharged on the same day as a day case. The families were
      given instructions to be followed for home care and emergency telephone numbers.
      In the time interval November 2000 to February 2001 43 patients aged between 2
      and 7 years were treated following this procedure for removal of a central venous
      catheter (16 patients), umbilical (2 patients) and inguinal (10 patients) hernia
      repair, and prepuce dorsal slit (15 patients). Anesthesia consisted of nasal
      premedication using midazolan, general inhalation anesthesia and peripheral
      locoregional block. RESULTS: The diagnosis of all chidren was confirmed. Only 1
      patient with upper airway infection was discovered. Recovery of all patients was
      uneventful. None of the patients called during the postoperative follow-up period
      for adverse events. CONCLUSIONS: Low costs and major parent and patient
      satisfaction are the main advantages of OSS, while the possible disadvantages are
      inaccurate referral for surgery and detection of contraindications for anesthesia
      at admittance to hospital. The authors recommend the use of wide scale OSS only
      when the operators have sound experience in pediatric day surgery.

PMID- 12792585
TI  - Sedation for Magnetic Resonance Imaging in a child affected with Williams
      syndrome.
AB  - Williams syndrome (WS) is a rare genetical disorder with an incidence of 20-50
      000 live births. It is caused by a delation of 1 elastin allele located within
      chromosome subunit 7q11.23 (long arm). It is characterized by: supravalvular
      aortic stenosis, multiple peripheral pulmonary artery stenosis, a typical face
      (elfine face), mental and statural deficiency, characteristic dental
      malformation, transient hypercalcemia that occurs during the 1(st) year of life.
      We present the case of a 7-month-old infant affected with WS. In order to clarify
      the cardiac findings, the baby under-went a MRI investigation, requiring an
      anesthesiological assistance. In this case a deep sedation approach was carried
      out by giving chloral hydrate 10% per os (80 mg/kg). We did not perform a general
      anesthesia in order to avoid the risk related to it. No other drugs were used.
      During the procedure SpO(2), HR, RR, and ETCO(2) were in normal range; ST tract
      analysis did not reveal any pathological change The examination lasted 95
      minutes; at the end the baby was kept under surveillance in the recovery room for
      30 minutes, he could be precociously fed. All the procedure was uneventful.

PMID- 12792584
TI  - Bedside burr hole for intracranial pressure monitoring performed by anaesthetist
      intensive care physicians. Extending the practice to the entire ICU team.
AB  - BACKGROUND: To evaluate the effects of extending the practice of bedside burr
      hole for intracranial pressure (ICP) monitoring to the entire ICU team. METHODS: 
      DESIGN: a 10-year observational cohort study. SETTING: A general-neurologic 12
      bed ICU of a University Hospital with 10 full-time specialists in anaesthesia
      intensive care. PATIENTS: patients admitted for acute neurologic lesions
      requiring ICP monitoring. MEASUREMENTS: ICP monitoring was performed by means of
      intraparenchymal fiberoptic cathe-ters. Rates of successfully performed
      procedures and complications were compared between 2 study periods: January 1990 
      August 1997, in which the procedure was performed by 2 experienced physicians
      (group 1), and September 1997-July 2000 in which the procedure was extended to
      the entire team (group 2). RESULTS: Two hundred and seventy patients had 293
      catheters positioned (group 1=180; 2=113). The procedure was successfully
      performed in all cases. Occurrence of complications was similar in the 2 groups:
      minor surgical wound infections (3.3%; 2.6%); meningitis (0.5%; 0); scalp (3.9%;
      2.6%) and dural (5.0%; 6.2%) bleeding; intracranial haematoma (1.1%; 1.8%). Two
      of these latter (1 for each group) required surgical evacuation. Twelve
      anaesthetist-intensive care physicians were trained, and they were able to
      perform burr hole for ICP monitoring without help after 2-3 assisted procedures.
      CONCLUSIONS: Extending the practice of ICP monitoring to the entire ICU team is
      safe and feasible. To decide whether or not to implement this technique, one
      should consider the high costs on one side and prompt availability of ICP
      monitoring on the other. Haemorrhagic and infectious complications are comparable
      to those of neurosurgical series.

PMID- 12792586
TI  - The role of the anesthetist in day-surgery services.

PMID- 12792589
TI  - Buckle tricks: keep those buckle straps out of the way.

PMID- 12792591
TI  - Arrhythmia recognition.

PMID- 12792594
TI  - Pain & comfort: the pathophysiology of pain & prehospital treatment options.

PMID- 12792595
TI  - Future trends in prehospital pain management.

PMID- 12792596
TI  - Myths of prehospital analgesia.

PMID- 12792597
TI  - The face of pain: how to assess & manage patient pain in the field.

PMID- 12792598
TI  - Carbon monoxide detection: colorless, odorless detector: the GasProbe CO.

PMID- 12792599
TI  - Emergency messaging & contingency communications.

PMID- 12792603
TI  - Quicksand airway.

PMID- 12792604
TI  - Taking WMD training to the students.

PMID- 12792606
TI  - Conflicting priorities, questions without easy answers: ethics and ADA.

PMID- 12792607
TI  - CEQ x 2: New continuing education questionnaire format debuts.

PMID- 12792609
TI  - Expanding Vitamin D fortification: a balance between deficiency and toxicity.

PMID- 12792610
TI  - September 11: two members look back, forward.

PMID- 12792611
TI  - A business rotation for dietitians--an imperative in the new millennium.

PMID- 12792612
TI  - Bioavailability of oxidized vitamin C (dehydroascorbic acid).

PMID- 12792613
TI  - Bioavailability of oxidized vitamin C (dehydroascorbic acid).

PMID- 12792616
TI  - How dietitians can make a difference through political action.

PMID- 12792617
TI  - Fostering healthy food consumption in schools: focusing on the challenges of
      competitive foods.

PMID- 12792618
TI  - Beverage choices of young females: changes and impact on nutrient intakes.
AB  - OBJECTIVE: To examine trends in beverage consumption and evaluate the impact of
      beverage choices on the nutrient intakes of females ages 12 to 19 years. DESIGN:
      Dietary intake data from the USDA's Nationwide Food Consumption Surveys,
      including the Continuing Survey of Food Intakes by Individuals (CSFII), were
      assessed for trends in beverage consumption. The CSFII 1994-1996 data was used to
      examine the diets of young females grouped based on their milk and soda
      consumption status. Mean energy, nutrient, and beverage intakes were compared.
      SUBJECTS: Females with complete dietary intake information on Day 1 of the survey
      were included in the study. There were 732 females ages 12 to 19 years in the
      CSFII 1994-1996. Statistical Analysis Percentages of females consuming specific
      beverages were estimated. Pairwise mean comparisons were made between groups
      based on milk and soda consumption status. RESULTS: Milk intakes decreased by 36%
      whereas that of sodas and fruit drinks almost doubled from the late 1970s to the
      mid 1990s. The CSFII 1994-1996 data showed that between ages 12 and 19 years,
      intakes of fruit juices, soda, tea, fruit drinks, and alcoholic beverages either
      increased or remained relatively steady, while milk intakes decreased with an
      increase in age. At age 12 years, 78% drank milk and had the lowest soda intake
      (276g), while at age 19-years, only 36% drank milk and drank a high amount of
      soda (423g). Those who did not drink milk had inadequate intakes of vitamin A,
      folate, calcium, phosphorus, and magnesium. APPLICATION: A rapid decrease in milk
      intake during the early adolescent years indicates a need for interventions at
      this age. Dietitians should identify barriers to drinking milk and recommend
      strategies for including appropriate food sources to increase calcium intakes
      during growing years. Nutrition educators should provide parents of adolescent
      children with ideas for ensuring the adequacy of their children's calcium
      intakes. J Am Diet Assoc. 2002; 102: 1234-1239.

PMID- 12792619
TI  - Where can I find information about packing a healthy and safe brown-bag lunch?

PMID- 12792620
TI  - Dietary patterns predict the development of overweight in women: The Framingham
      Nutrition Studies.
AB  - OBJECTIVE: To investigate relationships between dietary patterns and the
      development of overweight. DESIGN: Longitudinal analyses during 12 years of
      follow-up involved the identification of dietary patterns at baseline using
      cluster analysis applied to a 145-item semiquantitative food frequency
      questionnaire. SUBJECTS/SETTING: 737 non-overweight women in the Framingham
      Offspring/Spouse cohort (mean age, 45 years). MAIN OUTCOME MEASURE: Development
      of overweight (BMI> or =25) at follow-up. STATISTICAL ANALYSES: Relative risks
      were calculated using Proc Genmod and multivariate models comprehensively
      considered potential confounders. RESULTS: Five dietary patterns were identified
      among the cohort at baseline: Heart Healthy, Light Eating, Wine and Moderate
      Eating, High Fat, and Empty Calorie. Over 12 years, the crude risk of becoming
      overweight was 29% overall, ranging from 22% of women in the Wine and Moderate
      Eating cluster to 41% of women in the Empty Calorie cluster. Compared with women
      who ate a lower-fat, nutritionally varied Heart Healthy diet, women who ate an
      Empty Calorie diet that was rich in sweets and fats with fewer servings of
      nutrient-dense fruits, vegetables, and lean food choices were at higher risk for
      developing overweight [RR 1.4, 95% CI (0.9, 2.2)] after adjusting for age,
      smoking status, physical activity, menopausal status, energy intake, intentional
      dieting, and usual weight pattern. Women who ate an Empty Calorie dietary pattern
      were also younger and were more likely to smoke. CONCLUSIONS: Behavioral
      interventions for weight management and obesity prevention may be enhanced by
      creatively targeting differences in eating patterns, dietary quality, and other
      lifestyle behaviors of distinct subgroups of the population.

PMID- 12792621
TI  - Americans on diet: results from the 1994-1996 Continuing Survey of Food Intakes
      by Individuals.
AB  - OBJECTIVE: To examine the prevalence of dieting to lose weight or for a health
      reason in a representative sample of US adults. DESIGN: Cross-sectional study
      design. SUBJECTS/SETTING: Data from 10,144 participants of the 1994-1996
      Continuing Survey of Food Intakes by Individuals (CSFII 1994-1996) were used in
      the analysis. All data were self-reported. STATISTICAL ANALYSIS: Analysis
      included: cross-tabulation of dieting status by sociodemographic characteristics;
      comparison of the type of diet, the reason for dieting, and the source of diet
      used by men and women; comparison of the nutrient intake and health status of
      dieters and nondieters. RESULTS: Prevalence of dieting varied by gender and race,
      being highest in white women (21%) and lowest in Hispanic men (8%). About 71% of
      all dieters reported that they were dieting to improve health, and 50% reported
      that they were dieting to lose weight. Dieters reported lower intakes of total
      fat, saturated fat, cholesterol, sodium, monounsaturated fat, polyunsaturated
      fat, calcium, and selenium compared with nondieters. The rate of chronic health
      conditions was higher among dieters than nondieters. Self-reported physical
      activity was similar in both groups. CONCLUSIONS: The prevalence of dieting
      varies according to sociodemographic characteristics. The reason for dieting and
      the type of diet used by dieters also vary and need to be studied further. Our
      results suggest that the dieters generally consumed a more nutrient-dense diet
      than the nondieters but still low in certain nutrients.

PMID- 12792622
TI  - A low-fat intake and greater activity level are associated with lower weight
      regain 3 years after completing a very-low-calorie diet.
AB  - OBJECTIVE: To examine the roles of diet, exercise, and lifestyle factors in
      determining long-term weight regain after weight loss with a very-low-calorie
      diet (VLCD). SUBJECTS: Twenty-seven of 38 women who lost weight with a VLCD.
      DESIGN: Graduates of a weight loss intervention study returned for follow-up 3
      years after program completion. Percentage of initial weight loss that was
      regained was correlated with subjects' fat intake (assessed via 7-day food
      records and a Diet Habit Survey), energy intake (assessed via 7-day food
      records), activity level and lifestyle factors (assessed via questionnaires) that
      are supportive of weight loss maintenance. STATISTICAL ANALYSES PERFORMED:
      Regression analysis was used to assess the relationship of weight regain with fat
      intake, activity level, and energy intake. Contingency table analysis was used to
      assess the association between weight regain and lifestyle factors. RESULTS:
      Subjects followed experienced a -20.7kg+/-9.2kg (-19.2%+/-7%) (mean+/-standard
      deviation) weight change during the original VLCD program and a 13.9kg+/-11.3kg
      (76.6%+/-52.1%) weight change 3 years post-VLCD. Fat intake, assessed by a 7-day
      food diary, was positively correlated with weight regain at 3 years (r=0.66,
      P=.0004). Less weight regain was also seen with a lower percent fat intake as
      reflected by a higher Diet Habit Survey score (r=-0.55, P=.004). Women with the
      lowest tertile of reported fat intake (<25% of energy) from the Diet Habit Survey
      regained the least amount of weight (P=.05). Activity level was negatively
      correlated with weight regain (r=-0.53, P=.005). After correction for multiple
      comparisons, there was no association between total energy intake and weight
      regain. Lifestyle factors were also not associated with weight regain.
      APPLICATIONS/CONCLUSIONS: Identifying strategies to maintain weight loss is
      crucial because of the negative health effects and increasing prevalence of
      obesity. For women who have lost weight on a VLCD, limiting dietary fat intake
      and maintaining physical activity are both important factors for the prevention
      of weight regain. To promote better weight loss outcomes, registered dietitians
      should help clients who have lost weight limit their fat intake to less than 30%
      of energy and encourage high activity levels.

PMID- 12792623
TI  - Tomato consumption increases lycopene isomer concentrations in breast milk and
      plasma of lactating women.
AB  - OBJECTIVE: To compare plasma and milk lycopene concentrations and the changes in
      lycopene isomer patterns in lactating women before and after a 3-day dietary
      intervention with fresh or processed tomato products. DESIGN: Randomized
      prospective trial. SUBJECTS: 24 lactating women, 4 to 12 weeks postpartum, aged
      22 to 39 years. INTERVENTION: Subjects initially consumed a low-lycopene diet for
      7 days (washout period) and then were randomly assigned to one of 3 dietary
      groups (n=8 per group) without any other sources of lycopene: control (low
      lycopene), fresh tomatoes, or processed tomato sauce. Subjects in each of the
      tomato groups consumed approximately 50 mg total lycopene over 3 days. OUTCOME
      MEASURES: Before and after dietary intervention, plasma and breast milk samples
      were obtained for high-performance liquid chromotography analysis of lycopene and
      its geometric isomers (all-trans, 5-cis, all other cis, and total lycopene).
      STATISTICAL ANALYSIS: Descriptive statistics, analysis of variance to test for
      differences among intervention groups, and Spearman's correlation coefficients to
      test for blood-milk relationships. RESULTS: Plasma total lycopene and lycopene
      isomer concentrations increased in the fresh and processed tomato group but not
      in the low-lycopene control group during the study. Milk total and cis- and trans
      lycopene concentrations (unadjusted for fat) increased in the processed tomato
      group but did not change in the fresh tomato group. In the control group, milk
      total and trans-lycopene decreased. Milk total lycopene concentrations were not
      significantly different from baseline in any group when adjusted for fat content
      of milk. APPLICATIONS: The results of this study indicate that consumption of a
      "standard size portion" of tomato products increases plasma and milk lycopene
      concentrations in lactating women and, therefore, could increase the lycopene
      status of nursing infants. For dietary recommendations during lactation, the
      results suggest that consumption of tomato sauce increases milk lycopene
      concentrations more effectively than consumption of fresh tomatoes.

PMID- 12792624
TI  - Evidence-based medicine: applications in dietetic practice.
AB  - Evidence-based medicine has been defined as "the conscientious, explicit, and
      judicious use of current best evidence in making decisions about the care of
      individual patients." Evidence-based practice requires the ability to apply
      knowledge of medical informatics (eg, efficiently searching the medical
      literature) and clinical epidemiology (eg, being able to critically appraise the
      literature) to the treatment of individual patients. Being able to apply the
      principles of evidence-based medicine in the dietetic practice adds to the
      credibility and value of dietetics professionals, is consistent with the dietetic
      code of ethics, and is empowering. This article provides an introduction to the
      history, philosophy, and methods of evidence-based medicine as applied to the
      dietetic practice. This article focuses on a 5-step process to finding the best
      evidence to answer clinical questions: (a) formulate the question, (b) search for
      answers, (c) appraise the evidence, (d) apply the results, and (e) assess the
      outcome. We describe the 4S methodology-a systematic approach to efficiently
      finding the best evidence to answer clinical questions involving the use of
      systems (comprehensive, evidence-based resources), synopses (compilations of
      structured abstracts of high-quality studies), syntheses (systematic reviews),
      and studies (original research articles). Particular emphasis is given to a
      method for critically appraising papers that emphasizes validity, importance, and
      clinical applicability. Resources (including Web sites) for further learning are
      provided. J Am Diet Assoc. 2002;102:1263-1272.

PMID- 12792626
TI  - Relationship of folate to colorectal and cervical cancer: review and
      recommendations for practitioners.
AB  - Evidence suggests that folate may play a role in cancer prevention. A plausible
      mechanism for prevention lies in the integral role that folate plays in
      deoxyribonucleic acid (DNA) synthesis and methylation. DNA methylation most
      likely regulates gene expression. Abnormal methylation, specifically
      hypomethylation, has been associated with tumorigenesis. The availability of
      methyl groups needed for adequate DNA methylation may be negatively influenced by
      low folate status, alcohol intake, or genetic polymorphisms that affect folate
      metabolism. Observational studies evaluating the association between folate and
      risk for colorectal and cervical cancers or precancerous conditions have produced
      conflicting results, and clinical trial data are needed to confirm a cause-and
      effect relationship. However, several studies show interesting associations
      between cancer risk and factors that influence methyl group availability.
      Although data relating folate to cancer risk remain equivocal, when coupled with
      the other potential health benefits associated with folate, evidence supports
      recommending that people consume folate-rich foods such as fruits and vegetables.
      People consuming alcohol on a daily basis may especially benefit from additional
      folate in their diets.

PMID- 12792627
TI  - Students consuming sack lunches devote more time to eating than those consuming
      school lunches.
AB  - Concern has been raised about the amount of time provided for students to consume
      school lunch. This study analyzed the amount of time used by elementary students
      to consume school lunch vs sack lunch. Data collectors used stop watches to
      collect wait time, opportunity time to eat and consumption time for elementary
      students consuming school lunch, sack lunch, and sack lunch with a separate milk
      purchase. Students consuming school lunch had a significantly longer wait time
      than those consuming sack lunch or sack lunch with milk (P<.0001). In contrast,
      students consuming sack lunch and sack lunch with milk had significantly longer
      opportunity times to eat (P<.0001) and consumption times (P<.001). There was also
      a significant decrease in opportunity time to eat and consumption time as grade
      level increased, particularly in boys (P<.05). Older boys appeared more anxious
      to finish eating so they could go out to recess.

PMID- 12792628
TI  - Regional variations in dietary intake and body mass index of first-generation
      Asian-Indian immigrants in the United States.
AB  - Asian Indians (AIs) have considerable within-group diversity in education levels,
      socioeconomic status, language, and diet based on the region of origin in India.
      The objective of this study was to determine if dietary intake patterns vary
      based on region of origin among first generation AI immigrants and if these
      differences influence body mass index (BMI). AI men and women (n=237), over 40
      years, in southern US participated in a telephone survey. Responses to the Block
      food frequency questionnaire suggest that the diet of the study participants was
      low in dietary fiber while dietary fat intake was within guidelines. Intake of
      individual foods varied by region of origin. BMI also varied by region of origin
      (P<.05), with individuals from the north having a higher BMI (26.3) compared to
      those from the south and west (24.3). Regression analysis showed BMI to be
      significantly related to total fat intake, physical activity, and north region.
      Results suggest that dietary advice and lifestyle recommendations should be
      individualized.

PMID- 12792629
TI  - Predictors of breastfeeding duration for employees of the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC).
AB  - During the past decade there has been increasing breastfeeding support within the
      Women, Infants, and Children (WIC) program. For this study, it was hypothesized
      that employees at WIC would initiate and continue to breastfeed significantly
      longer than the National averages. Female employees, mostly paraprofessionals,
      from six Los Angeles County WIC agencies participated in the study to determine
      breastfeeding rates and predictors of breastfeeding success. As expected, 99% of
      WIC employees initiated breastfeeding and 68.6% continued to breastfeed to one
      year, significantly exceeding National averages. Four variables accounted for 30%
      of the variance in duration of breastfeeding: intent to exclusively breastfeed,
      delayed introduction of infant formula, attendance at breastfeeding support
      groups and availability of work-site breastpumps. Given that nearly 70% of the
      study participants reached the American Academy of Pediatrics goal of
      breastfeeding to 12 months or more, it is clear that full-time employment and
      breastfeeding can be compatible given appropriate work-site support.

PMID- 12792630
TI  - Eating behaviors, nutritional status, and menstrual function in elite female
      adolescent volleyball players.
AB  - Nutritional status, eating behaviors and menstrual function was examined in 23
      nationally ranked female adolescent volleyball players using a health/weight/
      dieting/menstrual history questionnaire, the Eating Disorder Inventory (EDI), and
      the Body Shape Questionnaire (BSQ). Nutrient and energy intakes (El) and energy
      expenditure (EE) were determined by 3-d weighed food records and activity logs.
      Iron (Fe), vitamins C, B12, and Folate status were assessed using serum and whole
      blood. Mean El (2248 +/- 414 kcal/d) was less than EE (2815 +/- 306 kcal/d). Mean
      carbohydrate (5.4 +/-1.0g/kg/d) and protein (1.1+/-0.3g/kg/d) intakes were below
      recommended levels for highly active women. Mean intakes for folate, Fe, Ca, Mg,
      and Zn were less than the respective RDAs/DRIs and almost 50% of the athletes
      were consuming less than the RDAs/DRIs for the B-complex vitamins and vitamin C.
      Three athletes presented with Fe deficiency anemia (Hb <12 mg/dL), while marginal
      vitamin B12 status (<200 pg/ml) and vitamin C status (<28 mmol/L) were found in 1
      and 4 athletes, respectively. Approximately 1/2 of the athletes reported actively
      "dieting". Mean BSQ and EDI subscales scores were within the normal ranges; yet,
      elevated scores on these scales were reported by 26% and 35% of athletes,
      respectively. Past or present amenorrhea was reported by 17% of the athletes and
      13% and 48%, reported past or present oligomenorrhea and "irregular" menstrual
      cycles, respectively. These results indicate that elite adolescent volleyball
      players are at risk for menstrual dysfunction and have energy and nutrient
      intakes that place them at risk for nutritional deficiencies and compromised
      performance.

PMID- 12792631
TI  - Effects of an educational program on intent to consume functional foods.
AB  - As consumers seek alternate ways to enhance health and prevent disease,
      incorporating functional foods into nutrition counseling and educational programs
      will become increasingly important. The Functional Foods for Health Program at
      the University of Illinois created and distributed 142 functional food
      educational kits to Illinois registered dietitians (RDs). Twenty-seven RDs
      presented the kits to consumer groups and returned 530 utilizable program
      evaluation/consumption questionnaires (370 females, 160 males). The food the
      highest percentage of participants ate daily was tomato products (18.8%),
      followed by garlic, broccoli, oats, yogurt, fish, grapes, tea, and soy. The foods
      the highest percentage of subjects consumed less than monthly were: soy (68.9%),
      tea (57.8%), grape (44.8%), and yogurt (25.9%). Following the education, at least
      74.9% intended to eat more tomatoes, grapes, oats, and broccoli. Our study
      demonstrates that age, gender, and awareness of health benefits dramatically
      influence intent to change dietary habits.

PMID- 12792632
TI  - Moisture retention and consumer acceptability of chocolate bar cookies prepared
      with okra gum as a fat ingredient substitute.
AB  - Low dietary fat intake may reduce the risk of developing atherosclerosis. This
      study determined the feasibility of using okra gum as a fat replacer in chocolate
      bar cookies. Fat-free cookies were prepared with okra gum (OK) or applesauce
      (AP), replacing margarine and egg yolk in high-fat cookies (CTL). The moisture
      content of cookies was determined by using a drying oven. The moisture contents
      of fresh OK (28.3+/-0.4%) and AP (27.6+1.1%) cookies were higher than CTL (8.5+/
      0.3%) and remained higher after 48 hours (P<.001)(n=3). Fifty-two consumers
      evaluated the quality of cookies using a hedonic scale. Sensory scores for color,
      smell, flavor, aftertaste, moistness, and overall acceptability for fresh cookies
      were acceptable, yet lower for flavor and aftertaste in fat-free cookies than CTL
      (P<.01). After 48 hours, moistness ratings for fat-free cookies were acceptable
      and higher than CTL (P<.01). Okra gum is an acceptable fat replacer in chocolate
      bar cookies.

PMID- 12792633
TI  - Performance, proficiency and value of the dietetics professional.

PMID- 12792634
TI  - Position of the American Dietetic Association: liberalized diets for older adults
      in long-term care.

PMID- 12792646
TI  - Re: Does fibrin glue reduce complications after femoral artery surgery? A
      randomised trial.

PMID- 12792647
TI  - X-ray microdiffraction study of growth modes and crystallographic tilts in oxide
      films on metal substrates.
AB  - The crystallographic texture of thin-film coatings plays an essential role in
      determining such diverse materials properties as wear resistance, recording
      density in magnetic media and electrical transport in superconductors. Typically,
      X-ray pole figures provide a macroscopically averaged description of texture, and
      electron backscattering provides spatially resolved surface measurements. In this
      study, we have used focused, polychromatic synchrotron X-ray microbeams to
      penetrate multilayer materials and simultaneously characterize the local
      structure, orientation and strain tensor of different heteroepitaxial layers with
      submicrometre resolution. Grain-by-grain microstructural studies of cerium oxide
      films grown on textured nickel foils reveal two distinct kinetic growth regimes
      on vicinal surfaces: ledge growth at elevated temperatures and island growth at
      lower temperatures. In addition, a combinatorial approach reveals that
      crystallographic tilting associated with these complex interfaces is
      qualitatively described by a simple geometrical model applicable to brittle films
      on ductile substrates. The sensitivity of conducting percolation paths to tilt
      induced texture improvement is demonstrated.

PMID- 12792648
TI  - Atomistic basis for the plastic yield criterion of metallic glass.
AB  - Because of their disordered atomic structure, amorphous metals (termed metallic
      glasses) have fundamentally different deformation mechanisms compared with
      polycrystalline metals. These different mechanisms give metallic glasses high
      strength, but the extent to which they affect other macroscopic deformation
      properties is uncertain. For example, the nature of the plastic-yield criterion
      is a point of contention, with some studies reporting yield behaviour roughly in
      line with that of polycrystalline metals, and others indicating strong
      fundamental differences. In particular, it is unclear whether pressure- or normal
      stress-dependence needs to be included in the plastic-yield criterion of metallic
      glasses, and how such a dependence could arise from their disordered structure.
      In this work we provide an atomic-level explanation for pressure-dependent yield
      in amorphous metals, based on an elementary unit of deformation. This simple
      model compares favourably with new atomistic simulations of metallic glasses, as
      well as existing experimental data.

PMID- 12792649
TI  - Histone H2AX phosphorylation is dispensable for the initial recognition of DNA
      breaks.
AB  - Histone H2AX is rapidly phosphorylated in the chromatin micro-environment
      surrounding a DNA double-strand break (DSB). Although H2AX deficiency is not
      detrimental to life, H2AX is required for the accumulation of numerous essential
      proteins into irradiation induced foci (IRIF). However, the relationship between
      IRIF formation, H2AX phosphorylation (gamma-H2AX) and the detection of DNA damage
      is unclear. Here, we show that the migration of repair and signalling proteins to
      DSBs is not abrogated in H2AX(-/-) cells, or in H2AX-deficient cells that have
      been reconstituted with H2AX mutants that eliminate phosphorylation. Despite
      their initial recruitment to DSBs, numerous factors, including Nbs1, 53BP1 and
      Brca1, subsequently fail to form IRIF. We propose that gamma-H2AX does not
      constitute the primary signal required for the redistribution of repair complexes
      to damaged chromatin, but may function to concentrate proteins in the vicinity of
      DNA lesions. The differential requirements for factor recruitment to DSBs and
      sequestration into IRIF may explain why essential regulatory pathways controlling
      the ability of cells to respond to DNA damage are not abolished in the absence of
      H2AX.

PMID- 12792650
TI  - Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.
AB  - Many pro-apoptotic signals activate caspase-9, an initiator protease that
      activates caspase-3 and downstream caspases to initiate cellular destruction.
      However, survival signals can impinge on this pathway and suppress apoptosis.
      Activation of the Ras-Raf-MEK-ERK mitogen-activated protein kinase (MAPK) pathway
      is associated with protection of cells from apoptosis and inhibition of caspase-3
      activation, although the targets are unknown. Here, we show that the ERK MAPK
      pathway inhibits caspase-9 activity by direct phosphorylation. In mammalian cell
      extracts, cytochrome c-induced activation of caspases-9 and -3 requires okadaic
      acid-sensitive protein phosphatase activity. The opposing protein kinase activity
      is overcome by treatment with the broad-specificity kinase inhibitor
      staurosporine or with inhibitors of MEK1/2. Caspase-9 is phosphorylated at Thr
      125, a conserved MAPK consensus site targeted by ERK2 in vitro, in a MEK
      dependent manner in cells stimulated with epidermal growth factor (EGF) or 12-O
      tetradecanoylphorbol-13-acetate (TPA). Phosphorylation at Thr 125 is sufficient
      to block caspase-9 processing and subsequent caspase-3 activation. We suggest
      that phosphorylation and inhibition of caspase-9 by ERK promotes cell survival
      during development and tissue homeostasis. This mechanism may also contribute to
      tumorigenesis when the ERK MAPK pathway is constitutively activated.

PMID- 12792652
TI  - IKKalpha: a chromatin modifier.

PMID- 12792651
TI  - Muscle stem cells differentiate into haematopoietic lineages but retain myogenic
      potential.
AB  - Muscle-derived stem cells (MDSCs) can differentiate into multiple lineages,
      including haematopoietic lineages. However, it is unknown whether MDSCs preserve
      their myogenic potential after differentiation into other lineages. To address
      this issue, we isolated from dystrophic muscle a population of MDSCs that express
      stem-cell markers and can differentiate into various lineages. After systemic
      delivery of three MDSC clones into lethally irradiated mice, we found that
      differentiation of the donor cells into various lineages of the haematopoietic
      system resulted in repopulation of the recipients' bone marrow. Donor-derived
      bone-marrow cells, isolated from these recipients by fluorescence-activated cell
      sorting (FACS), also repopulated the bone marrow of secondary, lethally
      irradiated, recipients and differentiated into myogenic cells both in vitro and
      in vivo in normal mdx mice. These findings demonstrate that MDSC clones retain
      their myogenic potential after haematopoietic differentiation.

PMID- 12792653
TI  - Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint
      blind DNA damage.
AB  - Cells maintain genomic stability by the coordination of DNA-damage repair and
      cell-cycle checkpoint control. In replicating cells, DNA damage usually activates
      intra-S-phase checkpoint controls, which are characterized by delayed S-phase
      progression and increased Rad53 phosphorylation. We show that in budding yeast,
      the intra-S-phase checkpoint controls, although functional, are not activated by
      the topoisomerase I inhibitor camptothecin (CPT). In a CPT-hypersensitive mutant
      strain that lacks the histone 2A (H2A) phosphatidylinositol-3-OH kinase (PI(3)K)
      motif at Ser 129 (h2a-s129a), the hypersensitivity was found to result from a
      failure to process full-length chromosomal DNA molecules during ongoing
      replication. H2A Ser 129 is not epistatic to the RAD24 and RAD9 checkpoint genes,
      suggesting a non-checkpoint role for the H2A PI(3)K site. These results suggest
      that H2A Ser 129 is an essential component for the efficient repair of DNA double
      stranded breaks (DSBs) during replication in yeast, particularly of those DSBs
      that do not induce the intra-S-phase checkpoint.

PMID- 12792654
TI  - X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher
      disease.
AB  - Gaucher disease, the most common lysosomal storage disease, is caused by
      mutations in the gene that encodes acid-beta-glucosidase (GlcCerase). Type 1 is
      characterized by hepatosplenomegaly, and types 2 and 3 by early or chronic onset
      of severe neurological symptoms. No clear correlation exists between the
      approximately 200 GlcCerase mutations and disease severity, although homozygosity
      for the common mutations N370S and L444P is associated with non- neuronopathic
      and neuronopathic disease, respectively. We report the X-ray structure of
      GlcCerase at 2.0 A resolution. The catalytic domain consists of a (beta/alpha)(8)
      TIM barrel, as expected for a member of the glucosidase hydrolase A clan. The
      distance between the catalytic residues E235 and E340 is consistent with a
      catalytic mechanism of retention. N370 is located on the longest alpha-helix
      (helix 7), which has several other mutations of residues that point into the TIM
      barrel. Helix 7 is at the interface between the TIM barrel and a separate
      immunoglobulin-like domain on which L444 is located, suggesting an important
      regulatory or structural role for this non-catalytic domain. The structure
      provides the possibility of engineering improved GlcCerase for enzyme-replacement
      therapy, and for designing structure-based drugs aimed at restoring the activity
      of defective GlcCerase.

PMID- 12792656
TI  - Preterm infant formula supplementation with alpha linolenic acid and
      docosahexaenoic acid.
AB  - OBJECTIVES: To investigate if supplementation of preterm infant formula with a
      high docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio together with
      alpha-linolenic acid (ALA) was able to maintain plasma and red blood cell DHA
      levels similar to that obtained with breast milk feeding without altering n-6
      fatty acid status. DESIGN AND SUBJECTS: Preterm infants of mothers who elected
      not to breast feed (n=13) were assigned to ALA- and DHA-enriched formula (DHA
      group: DHA/EPA=5/l). Infants fed breast milk (n=25) constituted a reference group
      (BM group). Anthropometric and fatty acid parameters (plasma phospholipids,
      cholesterol esters, triglycerides and red blood cell phosphatidylethanolamine,
      PL, CE, TG, RBC-PE, respectively) were obtained after 2 days (D2) and 15 days
      (D15) of enteral feeding and at the 37th week (W37) of post-conception age and 1
      month later (W37+30) in the DHA group. Mean DHA intake ranged between 16.5+/-1.6
      and 17.9+/-2.9 mg/kg/day between D2 and W37+30. RESULTS: At W37, infant weights,
      heights, and head circumferences were similar in DHA and BM groups. PL DHA was
      maintained in the DHA group at the same level as in the BM group and the same for
      DHA in PE at W37. In RBC-PE and at W37, AA status was the same in both groups. In
      PL, AA levels remained very stable throughout the study; however, in the DHA
      group AA levels in PL remained in the range observed with standard formulas.
      CONCLUSION: The combined 18:3 n-3 and DHA supplementation of infant formula with
      DHA/EPA ratio 5/l is compatible with growth and n-3 fatty acid metabolism similar
      to that of preterm infants fed human milk.

PMID- 12792655
TI  - Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of
      anthrax and Gram-positive pathogens.
AB  - The screening of new antibiotics against several bacterial strains often reveals
      unexpected occurrences of natural drug resistance. Two examples of this involve
      specific inhibitors of Staphylococcus aureus isoleucyl-transfer-RNA synthetase 1
      (IleRS1) and, more recently, Streptococcus pneumoniae methionyl-tRNA synthetase 1
      (MetRS1). In both cases, resistance is due to the presence of a second gene that
      encodes another synthetase (IleRS2 or MetRS2). Here, we show that both S.
      pneumoniae MetRS2 and S. aureus IleRS2 have closely related homologues in the
      Gram-positive bacterium Bacillus anthracis, the causative agent of anthrax.
      Furthermore, similar to drug-resistant pathogens, strains of B. anthracis and its
      closest relative, B. cereus, also have wild-type ileS1 and metS1 genes.
      Clostridium perfringens, the causative agent of gangrene, also has two metS
      genes, whereas Oceanobacillus iheyensis isolated from deep-sea sediments has a
      single ileS2-type gene. This study shows the importance of understanding complex
      evolutionary networks of ancient horizontal gene transfer for the development of
      novel antibiotics.

PMID- 12792658
TI  - Glycemic index of single and mixed meal foods among common Japanese foods with
      white rice as a reference food.
AB  - OBJECTIVE: The objectives were to examine the feasibility of using white rice as
      a reference food in the study of glycemic index (GI) and to examine the GI values
      of both single and mixed meal foods among rice species, processed rice products,
      beans, and dairy products. DESIGN: Subjects were served with 50 g carbohydrate
      content of white rice at least two times (maximum three times) and test food once
      after separate overnight fasts. Capillary blood glucose measurements were carried
      out before and during 120 min after each food load. SETTING: The study was
      carried out in an outpatient setting. SUBJECTS: A total of 58 (38 females and 20
      males) nondiseased subjects, mean aged 37 y and mean BMI 22 kg/m(2) were
      included. RESULT: The correlation between incremental area under curve of white
      rice and glucose was r=0.853 (n=10, P <0.0001) and white rice was considered
      suitable to be used as a reference food. Among mixed meal foods, the combination
      of carbohydrate foods with vinegar, dairy products, and bean products
      significantly decreased the GI value of white rice of 20-40%. The reduction of GI
      occurred whether the foods were taken together, before or after rice intake. GI
      of noodles such as udon, soba, and spaghetti showed low GI values. CONCLUSION:
      White rice could be used as a reference food in determining GI values of foods. A
      total of 32 single and mixed meal Japanese common food products were examined for
      their GI values.

PMID- 12792657
TI  - Difference in effect of myristic and stearic acid on plasma HDL cholesterol
      within 24 h in young men.
AB  - BACKGROUND: There is increasing evidence that postprandial triacylglycerol (TAG)
      rich lipoproteins (TRL) may be related to atherogenic risk. Little is known about
      the acute effect of individual dietary saturated fatty acids on plasma lipids and
      lipoproteins. OBJECTIVE: To investigate the effect of two prevalent dietary
      saturated fatty acids, stearic and myristic acid on postprandial and 24 h fasting
      plasma lipoprotein TAG and cholesterol concentrations. DESIGN: Ten young healthy
      men were served two meals (1.2 g fat/kg body weight) containing fat enriched in
      either stearic acid (S) (shea butter) or myristic acid (M) (produced by inter
      esterification) in a randomised, cross-over study. The meals were given in the
      morning after 12 h of fasting and again after 8 h (in the afternoon). The S and M
      containing meals were given at different days separated by a washout period.
      Blood samples were taken before the meal and 2,4,6,8, and 24 h after the first
      meal. RESULTS: The M meal resulted in a higher postprandial HDL TAG response than
      S (P=0.03 I), (diet x time interaction), while no differences were observed in
      other lipid fractions. Twenty-four hours after the M meal fasting, HDL
      cholesterol was higher (P=0.05) and HDL TAG lower (P<0.001) than at baseline.
      CONCLUSIONS: Intake of individual dietary SFA may affect fasting HDL cholesterol
      within 24 h. Thus after this short period HDL cholesterol concentration was
      higher after myristic acid than stearic acid. Myristic acid resulted in a higher
      increase in postprandial HDL TAG than stearic acid.

PMID- 12792659
TI  - Reliability of a dietary questionnaire on food habits, eating behaviour and
      nutritional knowledge of adolescents.
AB  - OBJECTIVE: To develop a dietary questionnaire on food habits, eating behaviour
      and nutrition knowledge of adolescents and to examine its reliability. DESIGN: A
      cross-sectional baseline survey. The questionnaire was self-administered to study
      participants twice with 7 days between each administration. SETTING: A school
      community in Pavia, Italy. SUBJECTS: A group of students (n=72, aged 14-17 y,
      both sexes) studying in a secondary school in the second year of the course were
      invited to compile a dietary questionnaire during school time. Informed written
      consent was obtained from each subject and their parents. Subjects were initially
      recruited for a nutrition intervention; recruitment was opportunistic and school
      based. STATISTICAL ANALYSES: Reliability was assessed using the Cronbach's alpha
      and the Pearson correlation coefficients. RESULTS: Cronbach's alpha ranges from a
      minimum of 0.55 to a maximum of 0.75, indicating that only two sections have a
      poor internal consistency. The Pearson correlation coefficients range from a
      minimum of 0.78 to a maximum of 0.88, indicating a very good temporal stability
      of the questionnaire. All the Pearson correlation coefficients are statistically
      significant with P<0.01. CONCLUSIONS: The present questionnaire has the potential
      to measure the effects of nutrition interventions on adolescents because of its
      stability in making comparisons over time. The instruments is low in cost and
      easy to administer and analyse; moreover, it could be modified appropriately to
      fit the needs of other populations as well.

PMID- 12792661
TI  - Evaluation of factors determining the precision of body composition measurements
      by air displacement plethysmography.
AB  - OBJECTIVES: To investigate methodological precision of air displacement
      plethysmography for assessment of body composition in a heterogenous sample of
      adults. DESIGN: Accuracy of volume measurements by air displacement
      plethysmography (ADP) for a range of known volumes was ascertained. Repeated
      measurements of body volume, lung volume, and derived body composition using the
      BODPOD measurement system were performed. Influence of surface area estimation on
      ADP measurement was investigated as a possible source of variation. SETTING:
      Clinical Nutrition Laboratory, School of Health & Sports Science, University of
      North London, London, UK. SUBJECTS: One hundred and two healthy subjects (57
      women, 45 men) who ranged in age between 16 and 55 y and in BMI (kg/m(2)) between
      17.8 and 41.9. STUDY DESIGN: Cross-sectional study of healthy adults for
      comparison with previous studies. Repeat measurements of raw body volume, lung
      volume and % body fat (BF) by ADP were all performed on the same day. RESULTS:
      From the range of known volumes a marked increase in the CV and a significantly
      greater measurement error were found at volumes below 40 l (P=0.04). Repeat
      measurements of raw body volume in human subjects resulted in a technical error
      equivalent to 0.8% BF. There was no significant difference found between measured
      and predicted lung volume and the 95% confidence interval for difference was only
      0.3% BF. Repeat measurements of lung volume in our subset resulted in a technical
      error equivalent to 0.5% BF. Although body surface area estimation only accounted
      for variation in % BF of 0.1%, the extent of variation appeared to be governed by
      leanness (P<0.001). CONCLUSIONS: Although ADP retains excellent precision, in
      practice, repeat measurements of ADP should be performed whenever possible to
      allow for erroneous volume measurement within one procedure. Protocols for ADP
      measurement should be created with an awareness of those factors, which may
      affect measurements. SPONSORSHIPS: This study was supported by the University of
      North London Diversity & Development Fund.

PMID- 12792660
TI  - Identifying adolescents with high percentage body fat: a comparison of BMI
      cutoffs using age and stage of pubertal development compared with BMI cutoffs
      using age alone.
AB  - OBJECTIVE: To ascertain whether body mass index (BMI) cutoffs calculated
      according to age and pubertal stage are superior to BMI cutoffs calculated on the
      basis of age alone at correctly identifying children and adolescents with high
      levels of adiposity. DESIGN: Cross-sectional study. SETTING: Dunedin, a
      university city in New Zealand. SUBJECTS AND MEASUREMENTS: In total, 368 healthy
      Caucasian children and adolescents (179 males, 189 females) aged 8.5-15.5 y had
      their percentage body fat measured by dual-energy X-ray absorptiometry (DXA).
      High adiposity was defined as > or =25% body fat in males and > or =35% body fat
      in females. The sensitivity, specificity and areas under the receiver operating
      characteristic curves of two Z-score distributions of BMI were calculated for
      each gender. RESULTS: Forty-nine males (27.3%) and 43 females (22.8%) had high
      DXA-measured percentage body fat. In all, 86% of males and females with high
      adiposity were correctly identified by BMI cutoffs calculated according to age
      alone, with 89% of males and 97% of females with low adiposity being correctly
      classified. Similar results were observed when BMI cutoffs utilising both age and
      stage of pubertal development were used; 90% of males and 88% of females with
      high adiposity and 92% of both males and females with low adiposity were
      correctly classified according to BMI. CONCLUSIONS: Categorisation of BMI
      according to both age and pubertal stage of development does not produce cutoffs
      that are superior to BMI cutoffs calculated on the basis of age alone at
      identifying children with high DXA-measured adiposity. SPONSORSHIP: University of
      Otago and the Health Research Council, New Zealand.

PMID- 12792662
TI  - Vitamins B6 and B12 and folate status in an adult Mediterranean population.
AB  - OBJECTIVE: To assess the nutritional status for vitamins B(6) and B(12) and
      folate in an adult Mediterranean population, in order to identify patterns of
      intake, groups at risk for deficiency, and factors that might influence this
      risk. DESIGN: A cross-sectional epidemiological survey. SETTING: Andalusia, a
      western Mediterranean region in southern Spain. SUBJECTS: The study was carried
      out with a random sample of 3528 subjects (1813 men, 1715 women) who were between
      25 and 60 y of age. Blood samples were obtained for biochemical assays in a
      random subsample of 384 subjects (183 men, 201 women). INTERVENTIONS: Food
      consumption was assessed by 48-h recall. Vitamin B(6) was measured as alpha
      erythrocyte aspartate aminotransferase activation coefficient (alphaEAST);
      vitamin B(12) and folate concentrations were measured in plasma. RESULTS: Energy
      and vitamin intakes were significantly higher in men than in women. In men,
      intakes were below two-thirds of the RDA in 10.8, 2.9 and 22.6% for B(6), B(12)
      and folate, respectively. The corresponding figures in women were 16.7, 5.1 and
      23.5% for vitamins B(6), B(12) and folate. Age, place of residence and
      educational level, alcohol use and smoking were also associated with differences
      in the intake of these nutrients. Biochemical analyses showed that vitamins B(6),
      B(12) and folate status was acceptable in 75.7, 89.1 and 57.6% of the population,
      respectively. Plasma concentration of folate was significantly higher in women.
      CONCLUSION: Our results provide a precise estimate of the nutritional status for
      vitamins B(6), B(12) and folate in the adult population of southern Spain.
      Factors such as age, place of residence, level of education and smoking can
      increase the risk of inadequate intake of some nutrients. However, these factors
      did not affect biochemical indexes of nutritional status in the present study.
      SPONSORSHIP: Direccion General de Salud Publica and the Health Council of the
      Andalusian Regional Government.

PMID- 12792663
TI  - Mothers of undernourished Jamaican children have poorer psychosocial functioning
      and this is associated with stimulation provided in the home.
AB  - OBJECTIVES: To compare mothers of undernourished children with mothers of
      adequately nourished children on maternal depression, parenting self-esteem,
      social support and exposure to stressors and to determine if these variables are
      independently related to undernutrition and stimulation provided in the home
      after controlling for socio-economic status. DESIGN: A case control study.
      SETTING: Children and their mothers were recruited from 18 government health
      centres in the Kingston, St Andrew and St Catherine parishes of Jamaica.
      SUBJECTS: One hundred and thirty-nine mothers of undernourished children (WAZ< or
      =-1.5z scores) aged 9 - 30 months and 71 mothers of adequately nourished children
      (WAZ > -1z scores) matched for sex and age group were enrolled into the study.
      RESULTS: Mothers of undernourished children came from poorer homes but had
      similar social support to mothers of adequately nourished children. They were
      more depressed, had lower levels of parenting self-esteem (both P<0.01), reported
      higher levels of economic stress (P<0.001) and provided a less stimulating home
      environment (P<0.05). However, after controlling for social background variables
      there was no independent relationship between either psychosocial function or
      home stimulation and nutritional status. Undernutrition was found to be mainly
      explained by economic factors. The mothers' self-esteem was independently
      associated with the level of stimulation provided to the child. CONCLUSIONS: When
      caring for undernourished children attention should be paid to the psychosocial
      status of the mother as well as the physical condition of the child. SPONSORSHIP:
      Thrasher Research Fund; Campus Research and Publication Fund, UWI, Jamaica.

PMID- 12792664
TI  - Increased lipid peroxidation during long-term intervention with high doses of n-3
      fatty acids (PUFAs) following an acute myocardial infarction.
AB  - OBJECTIVE: To assess the oxidative burden of a highly concentrated compound of n
      3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde
      complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins
      combined with n-3 PUFAs or corn oil. DESIGN: A prospective, randomised, double
      blind, controlled study. SETTING: One hospital centre in Stavanger, Norway.
      SUBJECTS: A total of 300 subjects with an acute myocardial infarction (MI).
      INTERVENTIONS: Gelatine capsules, containing 850-882 mg EPA and DHA as
      concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two
      capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all
      capsules to protect the PUFAs against oxidation. RESULTS: After 1 y TBA-MDA
      increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil
      group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in
      serum total phospholipids (n=56) on TBA-MDA measured after 12 months
      intervention, showed no dependency. Performing best subsets regression, serum
      phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as
      a predictor of TBA-MDA at 12 months follow-up, P=0.004. We found no impact of
      statins on TBA-MDA. CONCLUSION: TBA-MDA increased modestly after long-term
      intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological
      changes induced by n-3 PUFAs, rather than simply reflecting their concentration
      differences. The peroxidative potential of n-3 PUFAs was not modified by statin
      treatment. SPONSORSHIP: : Pharmacia A/S and Pronova A/S, Norway.

PMID- 12792665
TI  - Magnesium absorption from mineral water.

PMID- 12792666
TI  - Relationship between presenilinase and gamma-secretase.
AB  - Genetic and neuropathological studies suggest that processing of amyloid
      precursor protein (APP) to yield amyloid beta-protein (Abeta) plays an important
      role in the pathogenesis of Alzheimer's disease (AD). One of the current
      therapeutic efforts for AD is directed towards blocking the gamma-secretase
      activity that produces Abeta. Compelling evidence for presenilin (PS) possessing
      gamma-secretase activity includes a lack of Abeta production in PS knockout
      neurons and in cultured cells carrying a dominant negative mutation at either of
      two critical aspartate residues in PS, which may constitute the active site of
      gamma-secretase. In vitro studies have shown a binding of transition-state analog
      gamma-secretase inhibitors to PS N-terminal fragment (NTF) and C-terminal
      fragment (CTF), the functional form of PS detected in the high-molecular-weight
      gamma-secretase complex that also contains nicastrin, Aph-1 and PEN-2. Conversion
      of full-length PS into functional NTF and CTF is mediated by an unknown protease
      activity named presenilinase. Endoproteolysis of PS into NTF/CTF by presenilinase
      also requires two critical aspartate residues, suggesting that full-length PS may
      undergo autoproteolysis and PS itself is presenilinase. Similar to gamma
      secretase, presenilinase seems to be an aspartyl protease, as aspartyl protease
      inhibitor pepstatin A is the most potent inhibitor toward presenilinase among
      different classes of protease inhibitors. While several well-characterized gamma
      secretase inhibitors can block presenilinase activity in vivo and in vitro, the
      potency of inhibitors blocking presenilinase and gamma-secretase are not
      correlated. Lack of presenilinase inhibition by several potent gamma-secretase
      inhibitors suggests that these two protease activities are pharmacologically
      distinct.

PMID- 12792667
TI  - Involvement of hypocretins/orexins in sleep disorders and narcolepsy.
AB  - The orexins/hypocretins are novel peptide neurotransmitters first characterized
      in 1998. The cell bodies of the neurons releasing them are localized exclusively
      in the posterior and lateral hypothalamus although they send out projections
      which innervate the whole central nervous system. They have recently attracted a
      great deal of interest in the neuroscience and medical community due to the
      finding that a reduction of orexin/hypocretins levels occurs in most human cases
      of the sleep disorder narcolepsy. A flurry of recent experimental data has begun
      to shed light on the normal physiological functioning of this system and how its
      loss leads to narcolepsy. Preliminary findings also indicate that it may
      malfunction in a variety of other conditions where the normal sleep-wake cycle is
      compromised.

PMID- 12792669
TI  - Piscidins: a novel family of peptide antibiotics from fish.
AB  - The global emergence of many new infectious diseases, as well as concerns about
      the antibiotic resistance of an increasing number of microbial pathogens,
      necessitates that new approaches be sought in combating these serious infections.
      Peptide antibiotics, host-produced antimicrobial defenses that have been isolated
      from all types of organisms, from plants to mammals, possess a number of
      characteristics that make them attractive drug candidates. An example of the
      diversity and potential for new discoveries in this area is a novel family of
      peptide antibiotics named "piscidins," which have been recently isolated from
      fish. Piscidins have potent, broad-spectrum in vitro activity against many
      pathogens, including multidrug-resistant bacteria. Interestingly, piscidins
      reside in mast cells, a highly common tissue granulocyte of uncertain function
      that is ubiquitous in all vertebrate classes. The discovery of peptide
      antibiotics in mast cells may be a previously unappreciated, yet crucial,
      function for this highly common yet enigmatic immune cell.

PMID- 12792668
TI  - Participation of adenosine receptors in neuroprotection.
AB  - Adenosine is released from most cells, including neurons and glial cells. Once in
      the extracellular space, adenosine modifies cell functioning by operating G
      protein-coupled receptors. Interaction between adenosine receptors and other
      receptors for neuromodulators might contribute to a fine tuning of neuronal
      function, and therefore, to neuroprotection. Manipulation of adenosine receptors
      may influence sleep and arousal, cognition and memory, neuronal damage and
      degeneration and neuronal maturation. The therapeutic implications for
      neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease,
      epilepsy and multiple sclerosis are discussed.

PMID- 12792670
TI  - Chemogenomics knowledge-based strategies in drug discovery.
AB  - In the postgenomic age of drug discovery, targets can no longer be viewed as
      singular objects having no relationship to one another. All targets are now
      visible and the systematic exploration of selected target families appears to be
      a promising way to speed up and further industrialize target-based drug
      discovery. Chemogenomics refers to such systematic exploration of target families
      and aims to identify all possible ligands of all target families. Because biology
      works by applying prior knowledge to an unknown entity, chemogenomics approaches
      are expected to be especially effective within the previously well-explored
      target families, for which, in addition to the protein sequence and structure
      information, considerable knowledge of pharmacologically active structural
      classes and structure-activity relationships exists. For the new target families,
      chemical knowledge will have to be generated and beyond biological target
      validation, the emphasis is on chemistry to provide the molecules with which
      their novel biology and pharmacology can be studied. Using examples from the
      previously most successfully explored target families, the GPCR family in
      particular, we summarize herein our current chemogenomics knowledge-based
      strategies for drug discovery, which are founded on the high integration of chem
      and bioinformatics, thereby providing a molecular informatics frame for the
      exploration of the new target families.

PMID- 12792672
TI  - Modulation of vascular inflammation by PPARs.
AB  - The activation of cells in atherosclerotic lesions leads to the release of
      proinflammatory molecules and the onset of a chronic inflammatory response.
      Recent evidence suggests that peroxisome proliferator-activated receptors (PPARs)
      exert their antiinflammatory activities in vascular and immunological cell types
      such as endothelial cells, vascular smooth muscle cells and
      monocytes/macrophages. In these cells, PPARs regulate the gene expression of key
      proteins involved in the vascular inflammation contributing to atherogenesis. By
      modulating transcription of proinflammatory genes such as cytokines, chemokines,
      endothelial cell adhesion molecules and metalloproteinases, one can affect the
      events involved in atherogenesis, such as monocyte/macrophage and lymphocyte
      recruitment to the arterial wall and foam cell formation. Thus, PPAR agonists
      have emerged as a potential tool to modulate the inception and progression of
      atherosclerosis by exerting direct antiinflammatory and antiatherogenic actions
      at the level of the arterial wall. In this review, we will describe the current
      understanding of PPARs, the antiinflammatory activities of PPAR agonists and
      their proposed mechanisms of action.

PMID- 12792671
TI  - From neurodegeneration to neurohomeostasis: the role of ubiquitin.
AB  - Several years ago ubiquitin immunocytochemistry first demonstrated that ubiquitin
      protein conjugates are present in intraneuronal inclusions in all the major human
      chronic neurodegenerative diseases, as well as in inclusions in cerebellar
      astrocytomas and in hepatocytes in alcoholic liver disease. Unexpectedly, further
      studies showed that Lewy bodies are present in the cortex. Lewy bodies were
      originally described in the brain stem and are pathogonomic in the
      neuropathological diagnosis of Parkinson's disease. A balanced interpretation of
      further elegant experimental approaches, including transgenesis, suggests that
      the formation of intraneuronal inclusions is cytoprotective. Putative oligomeric
      proaggregates (prefibrillar entities) of cellular proteins inhibit the 26S
      proteasome and promote apoptosis. In the last few years a clutch of distinct
      experimental approaches have focused on the roles of ubiquitin-related processes
      in the development of the nervous system and neurohomeostasis. It is now clear
      that the ubiquitin/proteasome system (UPP) has a pivotal role in synaptogenesis,
      the formation of neuromuscular junctions and neurotransmitter receptor function.
      The inhibitory GABA(A) receptor, alpha1 glycine receptor, beta(2)-adrenergic
      receptor and arrestin, opiate receptors and the excitatory metabotropic glutamate
      receptor (mGluR1alpha) are regulated by the UPP. It is also increasingly clear
      that the regulation of long-term synaptic plasticity, and therefore memory, is
      dependent on both protein synthesis and protein degradation. Therefore, for the
      first time we have the opportunity to dissect the substrate of memory and the
      basis of cognitive decline in aging and in chronic neurodegenerative disease.
      Clearly, further understanding will provide a platform for novel drug development
      to treat chronic neurodegenerative diseases, including Alzheimer- and Parkinson
      related conditions, and possibly psychiatric disorders.

PMID- 12792673
TI  - Perspectives into the diversity of the U.K. pharmaceutical industry.
AB  - The Society for Medicines Research held a highly popular meeting in London in
      December 2002 entitled Trends in Medicinal Chemistry. The meeting was intended to
      alert researchers to some of the current areas of interest in the pharmaceutical
      industry either by highlighting some compounds in early development or exploring
      new discoveries likely to lead to new approaches to diseases treatment in the
      near future.

PMID- 12792674
TI  - [Disease globalization].

PMID- 12792675
TI  - [Culicidae mosquito abundance in a preserved metropolitan area and its
      epidemiological implications].
AB  - OBJECTIVE: To study the adult Culicidae fauna in a preserved area in urban
      outskirts for describing species of public health concern. METHODS: This study
      was developed in the Tiet  Ecological Park located in the outskirt of the city of
      S o Paulo, Brazil. Monthly collections were undertaken in three habitats at
      different times using electric aspirators and CDC and Shannon traps from August
      1996 to March 1998. Data analysis was based on estimates of frequencies and
      abundance. RESULTS: Twenty-five species or generic groups were identified among
      53,496 specimens collected. Ochlerotatus scapularis, Culex quinquefasciatus, and
      Culex declarator were the most frequent and abundant species. CONCLUSIONS: The
      most frequent and abundant species have been implicated in disease transmission
      to man in other regions. Attention must be given to these Culicidae since the
      study area is located near to an urban center, which could amplify the conditions
      for spreading vector diseases.

PMID- 12792676
TI  - [Parity and wind impact on the frequency of Anopheles marajoara, Sao Paulo,
      Brazil].
AB  - OBJECTIVE: To evaluate the impact of wind velocity on the behavior of An.
      marajoara population and its parity. METHODS: Collections were made bimonthly
      from January 1999 to February 2000 in the municipality of Ilha Comprida, Brazil.
      Adult mosquitoes were captured with a battery hand aspirator. Mann-Whitney test
      was applied to verify the wind impact on mosquito behavior. Polovodova technique
      and Christophers and Mer's follicular development analysis were used to determine
      parity. RESULTS: A total of 11,833 mosquitoes were captured, including 3,072 An.
      marajoara specimens. The peak of activity of An. marajoara occurred from 2 to 5
      AM. Amongst 1,006 An. marajoara females who had their ovarioles dissected, it was
      found 530 (52.7%) nulliparous, 432 (42.9%) uniparous, 24 (2.4%) biparous and 1
      multiparous. According to Christophers and Mer analysis, 982 (97.6%) had their
      follicles in phases I and II, 7 in phases III and IV, and 17 in phase V. The
      frequency of An. marajoara was significantly lower when wind velocity was 3 km/h
      or more or below 3 km/h. CONCLUSIONS: An. marajoara mosquitoes were more active
      at night. About 50% of dissected An. marajoara females were oniparous. Another
      important finding was the high proportion of females (97.6%) with follicles in
      the Christophers and Mer's phases I and II, suggesting the presence of
      gonotrophic concordance. Wind velocity equal or higher than 3 km/h considerably
      reduced the frequency of An. marajoara.

PMID- 12792677
TI  - [Survival of Aedes albopictus: physiological age and reproductive history].
AB  - OBJECTIVES: To study the longevity of Ae. albopictus populations in rural and
      urban areas in two different feeding conditions and to assess their physiological
      age and reproductive history. METHODS: Ae. albopictus larvae were collected in
      the Para ba Valley, (urban area) and Ribeira Valley (rural area), S o Paulo
      State, Brazil. In the laboratory, females were fed with sugar or blood and
      monitored daily. The day of death of each mosquito and other reproduction related
      characteristics were registered. Ovaries were dissected using Polovodova
      techniques and follicular development was examined according Christophers and
      Mer. Life tables were created and statistics analysis was performed for survival
      rates. Data analysis was carried out using Stata 7.0. RESULTS: Gonotrophic
      discordance was seen in both populations. Parous females developed terminal sacs.
      Nulliparous females had normal ovaries and in some cases dilatations were seen.
      Females fed with sugar showed higher survival rates. Statistical difference in
      survival rates was not observed in the populations of both areas. CONCLUSIONS:
      Parity status and physiological age of Ae. albopictus were not described using
      ovarioles analysis because they formed terminal sacs instead of dilations.
      Longevity of Ae. albopictus females was influenced by the food provided.

PMID- 12792678
TI  - [Validation of clinical and epidemiological diagnosis criterion for confirming
      cholera].
AB  - OBJECTIVE: To validate the clinical and epidemiological diagnosis criterion for
      confirming cholera suspect cases. METHODS: The study comprised 2,687 and 716
      patients admitted with diarrhea to a public hospital in Macei , Brazil, in 1992
      and 1997 respectively. Culture of V. cholerae O1 (Koch, 1884) in TCBS-agar was
      performed and the clinical and epidemiological criterion was applied and compared
      to the gold standard. The statistical analysis was carried out in two age-groups:
      less than five years old and five years old or more. RESULTS: There were studied
      833 patients, of which 517 in 1992 and 316 in 1997; 72 aged less than five years
      and 761 aged five years or more. In those aged less than five years in 1992,
      sensitivity was 40% and specificity 84.6%. For this same age-group in 1997,
      sensitivity was 28.6% and specificity 62.5%. In patients aged five years or more
      in 1992, sensitivity was 99% and specificity 1.2%. For this same age-group in
      1997, sensitivity was 86.9% and specificity 8.7%. CONCLUSION: The higher
      sensitivity of the clinical and epidemiological cholera diagnosis criterion in
      patients aged five years or more found in the study support its application
      during epidemics periods. In periods of lower incidence, all cases need to be
      confirmed using laboratory methods.

PMID- 12792679
TI  - [Change of the weight/ foot area coefficient in relation to aggregation in
      Tarebia granifera].
AB  - OBJECTIVE: To analyze specimens dispersion in a population of Tarebia granifera
      and its relationship with the change of morphometric parameters. METHODS: Two
      samplings by parcels including two types of substrata in opposite aggregation
      conditions were carried out, and the specimen abundance was compared between both
      samplings and substrata. The samples were stratified into classes according to
      shell height and for each of these the coefficient weight/foot-area was
      calculated and correlated with class size. It was experimentally evaluated
      whether specimens with a lower foot load had a better persistence in emerged
      substratum as well as the interaction between two class groups of shell height.
      RESULTS: The abundance difference between samplings was t=5.874 (p<0.001), and
      t=10.15 (p<0.001) between emerged rocky and sandy substrata, only under
      conditions of high aggregation where foot load decreases with the size for higher
      specimens (r=-0.98, p<0.05). Experimentally, the abundance of specimens of
      opposed sizes were mutually limited (r=-0.87, p<0.01), waves' height limits the
      abundance of smaller snails (r=-0.94, p<0.01) but it is tolerated by larger ones
      (r=0.72, p<0.05), and foot load diminishes with the waves' height (r=-0.93,
      p<0.001). CONCLUSIONS: Under high aggregation conditions larger specimens
      emigrate toward substratum of difficult capture by smaller ones, which are
      limited by the environment's mechanical influence. The decrease of foot load
      facilitates specimens' dispersion.

PMID- 12792680
TI  - [Prenatal care, low birth weight and prematurity in Sao Paulo State, Brazil,
      2000].
AB  - OBJECTIVE: The historical evolution of infant mortality rate and neonatal
      mortality according to birth weight and term of delivery in the state of S o
      Paulo are presented to assess the role of the number of prenatal visits and
      others factors for determining mortality. METHODS: Based on data available from
      the Seade Institute of Vital Statistics, four variables (maternal age, marital
      status, education, and childbirth order) were analyzed and divided into two
      categories according to the relative risk of low birth weight and/or preterm
      prevalence. Sixteen specific groups were created from crossing the four variables
      into two categories. Low birth weight and/or preterm prevalence per number of
      prenatal visits and the relative risk were calculated for all sixteen groups.
      RESULTS: For all sixteen groups, the higher the number of prenatal visits the
      lower the prevalence of low birth weight and/or prematurity. Additionally, there
      was an overall reduction of the difference of low birth weight and/or preterm
      prevalence among the 16 groups from 14% to 4% with an increase from 0-3 to 7
      visits or more. CONCLUSIONS: Due to the current infant mortality composition in
      the state of Sao Paulo, increasing the number of prenatal visits and
      accessibility of women at risk would probably lead to a reduction in intrauterine
      growth retardation, prematurity, low birth weight and deaths associated to
      conditions originated in the perinatal period.

PMID- 12792681
TI  - [Prognostic factors for cognitive development of very low birth weight premature
      children].
AB  - OBJECTIVE: Very low birth weight premature children often show cognitive
      development abnormalities. There is scarce information about the outcome of these
      children at preschool age in Brazil. The objective of the study is to describe
      the cognitive development of a population of premature newborns and to assess
      possible prognostic factors for abnormalities. METHODS: A cohort study was
      conducted in a preschool children population whose subjects were very low birth
      weight premature babies born between January 1991 and September 1993. WPPSI-R
      Test was used for cognitive evaluation and it was applied by psychologists. Two
      cut-offs were set to describe abnormality: scores below 1 and 2 standard
      deviations (SD). RESULTS: Seventy-nine children aged 4 and 5 years were studied.
      The mean full WIPPSI-R score was 75.6 (+/-11.9). The incidence of abnormal 1 and
      2 SD full score was 77.2% and 32.9%, respectively. After adjusting for the method
      of delivery, small for gestational age (OR=6.19, 95% CI 1.60-23.86), abnormal
      cerebral ultrasound exam (OR=5.90, 95% CI 1.04-9.83) and male sex (OR=3.20, 95%
      CI 1.32-26.35) were predictors of full score <70. CONCLUSIONS: Compared to the
      literature, these children showed a more severe cognitive development impairment.
      Small for gestational age, abnormal cerebral ultrasound exam and male sex were
      prognostic factors for worse outcome.

PMID- 12792682
TI  - [Impact estimates of breastfeeding over infant mortality].
AB  - OBJECTIVE: Infant mortality in the state of Sao Paulo has decreased in the last
      years and it seems to be leveling off at a limit beyond which further reductions
      are challenging. Early neonatal causes account for 50% of these deaths and the
      remaining are mostly due to pneumonia and diarrhea. This study is to assess the
      impact of breastfeeding over death reduction. METHODS: Fourteen municipalities of
      greater Sao Paulo were studied. Data on breastfeeding was collected through
      surveys conducted on national immunization campaign days and mortality data was
      taken from 1999 and 2000 official records. Drawing from literature parameters on
      risk for death from respiratory infection and diarrhea in non-breastfed infants,
      fractions of mortality preventable by breastfeeding were calculated. These
      figures applied to the number of recorded deaths allowed assessing the impact of
      breastfeeding over mortality for each municipality. RESULTS: Fractions of
      respiratory infection mortality preventable by breastfeeding varied according to
      locality and age group between 33% and 72%. As to diarrhea, variation was between
      35% and 86%. The impact of breastfeeding over infant mortality was an average
      reduction of 9.3% with values raging from 3.6% to 13%, depending on the locality
      considered. CONCLUSIONS: Breastfeeding in the first year of life might be the
      most feasible strategy to further reduce the current levels of infant mortality
      in the state of Sao Paulo.

PMID- 12792683
TI  - [Tuberculosis in Havana City, 1995-1999].
AB  - OBJECTIVE: Tuberculosis is a worldwide health problem getting a prioritized
      attention by the Cuban National Health System. To describe the main indicators of
      the Cuban Tuberculosis Control Program. METHODS: Based on surveillance data from
      the Provincial Center of Hygiene and Epidemiology, the health care network and
      strategies of the tuberculosis control program were reviewed; incidence rates,
      case finding indicators, diagnosis and case management were described. RESULTS:
      Eight subjects with respiratory symptoms were found per 1,000 attending general
      medical care services. The incidence rates of all tuberculosis types declined
      from 16.4 in 1995 to 12.0 x 10(5) people in 1999. Pulmonary tuberculosis
      incidence rate was reduced from 15.1 in1995 to 10.4 x 10(5) in 1999, whereas
      extrapulmonary tuberculosis had an increment from 1.3 to 1.6 x 10(5) in the same
      period. Of all new cases, 40-50 % were diagnosed at multispecialty clinics, 67.6%
      were diagnosed by positive smears, 15.2 % by positive cultures, 13.8 % by
      clinical and X-rays evidences only; and 0.9 % and 1.5 % were respectively
      diagnosed by biopsy and necropsy. There was an increase in the incidence rate in
      the age group 15-64 years in 1996 and 1997 but it declined again in 1998 and
      1999. The age group 64 years and over showed a rate reduction from 1995 to 1999.
      In general, incidence rates diminished in the overall period. The average delay
      between onset of symptoms and diagnosis improved from 42 days in 1995 to 28.6
      days in 1999. CONCLUSIONS: There seems to be a halt in reporting trends of new
      cases in 1996. Tuberculosis indicators reveal satisfactory changes in the study
      period.

PMID- 12792684
TI  - [Hepatitis B vaccination among dentists surgeons].
AB  - OBJECTIVE: Serological studies in several countries have found a higher
      prevalence of hepatitis B virus (HBV) among dentists when compared to the general
      population, especially among surgical specialties. The present study was carried
      out to determine the prevalence of hepatitis B (HB) vaccination and factors
      associated with no vaccination and incomplete vaccination among dentists.
      METHODS: A survey was conducted among 299 dentists living in Montes Claros,
      southeast Brazil, using a self-administered questionnaire. HBV vaccination
      prevalence was determined according to the number of doses of vaccine and factors
      associated with no vaccination or incomplete HBV vaccination were investigated
      using multinomial logistic regression analysis. RESULTS: Participation rate in
      the study was very high (296/299). Of the participants, 74.9% received three
      doses of HBV vaccine, 14% two doses, 2% a single dosis and 10% were not
      vaccinated. Complete vaccination rate was higher among surgeons and periodontists
      (89%). The main reason reported for not being vaccinated or incomplete
      vaccination was the need of more information. No vaccination was significantly
      higher among dentists aged 40 years and over (OR=8.62; 95%CI: 1.88-39.41) and
      those who did not attend refreshment courses in the last two years prior to the
      survey (OR=2.72; 95%CI: 1.02-7.22). Incomplete vaccination was positively
      associated with non-use of gloves during work (OR=2.32; 95%CI: 1.08-4.97).
      CONCLUSIONS: Lack of information, possibly associated to lower attendance to
      refreshment courses, seems to be one of the main factors affecting the
      vaccination rate.

PMID- 12792685
TI  - [Prevalence of hepatitis B, hepatitis C and syphilis in female sex workers in
      Venezuela].
AB  - OBJECTIVE: In Venezuela, female sex workers are submitted to a preventive control
      of syphilis and human immunodeficiency virus (HIV). However, other very important
      sexually transmitted infections are not evaluated. A study was carried out to
      identify the sociocultural background of a group of sex workers and its
      association with the seroprevalence of hepatitis B and C markers, in addition to
      routine evaluation. METHOD: A total of 212 female sex workers who attended the
      control center of sexually transmitted infections (STI) in the city of Los
      Teques, Venezuela, were evaluated. Women were asked their age, educational
      background, use of contraceptive methods and condoms. Blood was drawn to
      determine the prevalence of syphilis, hepatitis B surface antigen (HBsAg),
      antibodies to hepatitis B core (anti-HBc), hepatitis C (anti-HCV) and HIV.
      RESULTS: The prevalence of syphilis was 2.4%, seroprevalence of anti-HCV was
      0.5%, HBsAg 3.8% and anti-HBc 13.8%. No cases of HIV were observed. Higher
      prevalence of hepatitis B markers was associated with a lower level of education
      (p<0.05) and higher age (p<0.05). It was found that 38.5% of participant women
      never used condoms and 25.6% did not use any contraceptive method. CONCLUSION: It
      could be necessary to implement preventive programs to immunize sex workers
      against hepatitis B virus as well as education programs on condom use for their
      protection against sexually transmitted infections.

PMID- 12792687
TI  - Occupational accidents among middle and high school students of the state of Sao
      Paulo, Brazil.
AB  - OBJECTIVES: To estimate the prevalence of occupational injuries and identify
      their risk factors among students in two municipalities. METHODS: A cross
      sectional survey was conducted in public schools of the municipalities of Santo
      Antonio do Pinhal and Monteiro Lobato, Brazil. A stratified probabilistic sample
      was drawn from public middle and high schools of the study municipalities. A
      total of 781 students aged 11 to 19 years participated in the study. Students
      attending middle and high school answered a comprehensive questionnaire on living
      and working conditions, as well as aspects of work injuries, and health
      conditions. Multiple logistic regression models were fitted to estimate risk
      factors of previous and present occupational injuries. RESULTS: Of 781 students,
      604 previously had or currently have jobs and 47% reported previous injuries.
      Among current workers (n=555), 38% reported injuries on their current job. Risk
      factors for work injuries with statistically significant odds ratio >2.0 included
      attending evening school, working as a housekeeper, waiter or brickmaker, and
      with potentially dangerous machines. CONCLUSIONS: The study results reinforce the
      need of restricting adolescent work and support communities to implement social
      promotion programs.

PMID- 12792686
TI  - [Occurrence of diabetes mellitus in women with prior gestational hyperglycemia].
AB  - OBJECTIVE: To estimate the prevalence of glucose intolerance (diabetes mellitus
      and impaired glucose tolerance) in women who had their glucose tolerance
      evaluated and followed up during pregnancy. METHODS: Over the last 12 years since
      the index pregnancy, from a total of 3,113 pregnant women seen in an obstetrics
      clinic, 551 were randomly selected and proportionally to the number of women in
      each group. Of these, 529 could be evaluated and had been classified as follows:
      250 in group IA (normal glucose tolerance); 120 in group IB (daily
      hyperglycemia); 72 in group IIA (abnormal oral glucose tolerance test); and 87 in
      group IIB (abnormal oral glucose tolerance test and daily hyperglycemia). The
      evaluation consisted of measuring fasting plasma glucose and when the results
      ranged between 6.1 and 6.9 mmol/L, patients were submitted to oral glucose
      tolerance test. RESULTS: Prevalence of diabetes mellitus was: IA, 1.6%; IB,
      16.7%; IIA, 23.6%; and IIB, 44.8% (IA < [IB = IIA] < IIB; p<0.05). This
      difference between the groups remained the same for the eight years. Women in IA
      group were different from others regarding age, parity, and diabetes family
      history. CONCLUSION: Hyperglycemia (high plasma glucose levels) and abnormal oral
      glucose tolerance test during pregnancy are equally effective in predicting the
      risk for developing maternal diabetes. When both tests are abnormal, this risk is
      much higher.

PMID- 12792688
TI  - [Suicide mortality: gender and socioeconomic differences].
AB  - OBJECTIVE: To describe suicide mortality trend and sociodemographic patterns
      identifying gender and socioeconomic differences. METHODS: The trend of crude
      rates of suicide mortality by sex in the city of Campinas, Brazil, for the period
      1976-2001 was assessed. Data from the Mortality Registry were used for
      sociodemographic analyses in the period 1996-2001. An ecological approach was
      used to examine socioeconomic differences and the 42 city areas of health care
      units were classified into 4 homogeneous strata. Rates were age-adjusted using
      direct method. RESULTS: The city has a low suicide rate (less than 5/100,000) in
      comparison with other countries. Male excess mortality was over 2.7 male suicides
      for each female suicide. While in 1980-1985 the older group (55 years and older)
      had the highest suicide rates, in 1997-2001 the middle-aged adult group (35-54
      years old) showed the highest ones. As for suicide methods, men used hanging
      (36.4%) and firearms (31.8%), while women used poisoning (24.2%) and firearms and
      hanging (21.2% each). Hangings led to death at home, while firearms or poisoning
      deaths took place more often in hospitals. Suicide is different from homicide in
      that there is no rate increase with lower socioeconomic level. CONCLUSIONS:
      Suicide rates are low with successive increments and decrements without
      consistent growing or lowering trends. The risk of dying by suicide is higher
      among men and does not increase with lower socioeconomic condition.

PMID- 12792689
TI  - [Quality of life and well-being of elderly people: an exploratory study in the
      Portuguese population].
AB  - OBJECTIVES: To characterize elderly people's perception of quality of life and
      well-being. METHODS: A sample of 1,665 elderly aged 75 years or more living in 13
      districts in Portugal were studied. Of them, 311 subjects were excluded because
      they were not able to convey their opinions. The EASYcare (Elderly Assessment
      System) was used to collect data from 1,354 (81.3%) of 1,665 subjects.
      Statistical analysis was based on principal components analysis and cluster
      analysis. RESULTS: EASYcare's showed to have good psychometric proprieties
      (Cronbach a =0.92). The principal component analysis identified 4 factors:
      mobility, communication competencies, well-being and daily living activities.
      Cluster analysis showed 4 groups of elderly people: autonomous (62.8%), almost
      autonomous (8.5%), almost dependent (4.3%) and dependent (3.2%). CONCLUSIONS:
      Quality of life for most of the elderly is quite positive, and only a small group
      presents problems related to severe cognitive impairment or some degree of
      dependence.

PMID- 12792690
TI  - Outpatient health service utilization and associated factors: a population-based
      study.
AB  - OBJECTIVE: To identify factors that lead people to visit a doctor in Brazil and
      assess differences between socioeconomic groups. METHODS: A cross-sectional study
      comprising 1,260 subjects aged 15 or more was carried out in southern Brazil.
      Demographic, socioeconomic, health needs and regular source of care data were
      analyzed concerning visits to a doctor within two months from the interview.
      Adjusted prevalence ratios and 95% confidence intervals were calculated using
      Poisson regression. RESULTS: Adjusted PR showed that women having stressful life
      events, health insurance, and a regular doctor increased the outcome. A dose
      related response was found with self-reported health, and the probability of
      visiting a doctor increased with health needs. Analysis in the chronic disease
      group revealed that uneducated lower income subjects had a 62% reduction in the
      chance of visiting a doctor compared to uneducated higher income ones. However,
      as it was seen a significant interaction between income and education, years of
      schooling increased utilization in this group. CONCLUSIONS: Results suggest the
      existence of health inequity in the poorest group that could be overcome with
      education. Specific measures reinforcing the importance of having a regular
      doctor may also improve access in the underserved group.

PMID- 12792691
TI  - [Test-retest reliability of measures of social network in the "Pro -Saude"
      Study].
AB  - OBJECTIVE: To evaluate test-retest reliability of social network-related
      information of the" Pr -Sa de" study. METHODS: A test-retest reliability study
      was conducted using a multidimensional questionnaire applied to a cohort of
      university employees. The same questionnaire was filled out twice by 192 non
      permanent employees with two weeks apart. Agreement was estimated using kappa
      statistics (categorical variables), weighted kappa statistics, log-linear models
      (ordinal variables), and intraclass correlation coefficient (discrete variables).
      RESULTS: Estimates of reliability were higher than 0.70 for most variables.
      Stratified analyses revealed no consistently varying patterns of reliability
      according to gender, age or schooling strata. Log-linear modelling showed that,
      for the study ordinal variables, the model of best fit was "diagonal agreement
      plus linear by linear association". CONCLUSIONS: The high level of reliability
      estimated in this study suggests that the process of measurement of social
      network-related aspects was adequate. Validation studies, which are currently
      being conducted, will complete the quality assessment of this information.

PMID- 12792692
TI  - Aedes albopictus may not be vector of dengue virus in human epidemics in Brazil.
AB  - Over 60,500 dengue cases were reported in the state of Espirito Santo (ES),
      Brazil, between 1995 and 1998. The study's purpose was to identify whether Aedes
      albopictus was transmitting the dengue virus during an epidemic in the locality
      of Vila Beth nia (Viana County),Vitoria, ES. From April 3 to 9, 1998, blood and
      serum samples were collected daily for virus isolation and serological testing.
      Four autochthonous cases were confirmed through DEN 1 virus isolation and two
      autochthonous cases through MAC ELISA testing. Of 37 Ae. aegypti and 200 Ae.
      albopictus adult mosquitoes collected and inoculated, DEN1 virus was isolated
      only from a pool of two Ae. aegypti female mosquitoes. The study results suggest
      that Ae. albopictus still cannot be considered an inter-human vector in dengue
      epidemics in Brazil.

PMID- 12792693
TI  - [Occurrence of Aedes albopictus in the state of Para, Brazil].
AB  - It is first reported the detection of Aedes (Stg) albopictus mosquitoes in state
      of Par , Brazil, in the urban area of Medicil ndia, a municipality far 90 km from
      Altamira, where 42 adult mosquitoes were baited using human attraction. All
      mosquitoes were pooled and inoculated into C6/36 and suckling mice in attempts
      for virus isolation. No virus was isolated. The occurrence of Aedes albopictus in
      urban areas of the Amazon region is of concern since dengue and yellow fever
      viruses are endemic in the Amazon and thus there is a potential risk for this
      mosquito species to become infected with both viruses.

PMID- 12792694
TI  - Performance of an immunochromatography test for vivax malaria in the Amazon
      region, Brazil.
AB  - The study was carried out to evaluate the diagnostic performance of the ICT
      malaria Pf/Pv test for vivax malaria diagnosis in Bel m, Amazon region, Brazil.
      The results of blood malaria parasites examination using an immunochromatography
      test were compared with thick blood film (TBF) examination. It was also evaluated
      the performance of this test storaged at three different temperatures (25 degree
      C, 30 degree C, and 37 degree C) for 24 hours before use. Overall sensitivity of
      ICT Pf/Pv was 61.8% with a specificity of 100%, positive and negative predictive
      value of 100% and 71.8%, respectively and accuracy of 80.6%. The test sensitivity
      was independent of the parasite density. This test needs to be further reviewed
      in order to have better performance for P. vivax malaria diagnosis.

PMID- 12792695
TI  - Medical applications of shape memory alloys.
AB  - Shape memory alloys (SMA) are materials that have the ability to return to a
      former shape when subjected to an appropriate thermomechanical procedure.
      Pseudoelastic and shape memory effects are some of the behaviors presented by
      these alloys. The unique properties concerning these alloys have encouraged many
      investigators to look for applications of SMA in different fields of human
      knowledge. The purpose of this review article is to present a brief discussion of
      the thermomechanical behavior of SMA and to describe their most promising
      applications in the biomedical area. These include cardiovascular and orthopedic
      uses, and surgical instruments.

PMID- 12792696
TI  - Dietary cellulose has no effect on the regeneration of hemoglobin in growing rats
      with iron deficiency anemia.
AB  - The objective of the present study was to determine the effect of cellulose on
      intestinal iron absorption in rats during recovery from iron deficiency anemia.
      Twenty-one-day-old male Wistar-EPM rats were fed an iron-free ration for two
      weeks to induce anemia. At 5 weeks of age, the rats were divided into two groups
      (both groups receiving 35 mg of elemental iron per kg diet): cellulose group (N =
      12), receiving a diet containing 100 g of cellulose/kg and control (N = 12),
      receiving a diet containing no cellulose. The fresh weight of the feces collected
      over a 3-day period between the 15th and 18th day of dietary treatment was 10.7
      +/- 3.5 g in the group receiving cellulose and 1.9 +/- 1.2 g in the control group
      (P<0.001). Total food intake was higher in the cellulose group (343.4 +/- 22.0 g)
      than in the control (322.1 +/- 13.1 g, P = 0.009) during the 3 weeks of dietary
      treatment. No significant difference was observed in weight gain (cellulose group
      = 132.8 +/- 19.2, control = 128.0 +/- 16.3 g), hemoglobin increment (cellulose
      group = 8.0 +/- 0.8, control = 8.0 +/- 1.0 g/dl), hemoglobin level (cellulose
      group = 12.3 +/- 1.2, control = 12.1 +/- 1.3 g/dl) or in hepatic iron levels
      (cellulose group = 333.6 +/- 112.4, control = 398.4 +/- 168.0 g/g dry tissue). We
      conclude that cellulose does not adversely affect the regeneration of hemoglobin,
      hepatic iron level or the growth of rats during recovery from iron deficiency
      anemia.

PMID- 12792697
TI  - Thalassemia intermedia as a result of heterozygosis for beta 0 -thalassemia and
      alpha alpha alpha anti-3,7 genotype in a Brazilian patient.
AB  - We report a case in which the interaction of heterozygosis for both the 0-IVS-II
      1 (G->A) mutation and the alpha alpha alpha anti-3,7 allele was the probable
      cause for the clinical occurrence of thalassemia intermedia. The propositus, a 6
      year-old Caucasian Brazilian boy of Portuguese descent, showed a moderately
      severe chronic anemia in spite of having the -thalassemia trait. Investigation of
      the alpha-globin gene status revealed heterozygosis for alpha-gene triplication
      (alpha alpha alpha / alpha alpha). The patient's father, also presenting mild
      microcytic and hypochromic anemia, had the same alpha and genotypes as his son,
      while the mother, not related to the father and hematologically normal, was also
      a carrier of the alpha alpha alpha anti-3,7 allele. The present case emphasizes
      the need for considering the possibility of alpha-gene triplication in 
      thalassemia heterozygotes who display an unexpected severe phenotype. The 
      thalassemia mutation found here is being described for the first time in Brazil.

PMID- 12792698
TI  - Acute myeloid leukemia in elderly patients: experience of a single center.
AB  - Acute myeloid leukemia (AML) is a disease predominantly of older adults.
      Treatment of AML in the elderly is complicated not only by comorbidities but also
      by the high prevalence of poor prognosis markers. Thirty-one consecutive
      unselected patients with AML older than 60 years (representing 33% of all AML
      cases diagnosed at our institution during the same period) were followed over a
      period of 5 years (1997-2002). A high incidence of AML with multilineage
      dysplasia (45%) and no favorable cytogenetic abnormalities but 62% intermediate
      and 38% unfavorable karyotypes were found. Sixteen patients (52%) were selected
      for induction of intensive cytotoxic treatment and complete remission was
      achieved only by some of these intensively treated patients (7 of 16). Of these,
      3 remained alive without disease (median: 11 months), 1 patient died shortly
      after complete remission, and 3 patients relapsed and died from refractory
      disease. Only 1 patient that was refractory to intensive cytotoxic treatment
      remained alive with disease under supportive care. Fifteen patients (48%) were
      managed with palliative/supportive care: 7 received palliative treatment and
      supportive care, 8 received supportive care only, and 4 patients remained alive
      with disease under supportive care (median: 9 months). Mortality rate was 74% and
      overall survival at two years was 12%. To the best of our knowledge, there is no
      previous report regarding elderly patients with AML in Brazilian subsets. The
      present data are similar to previously reported studies showing that elderly AML
      patients are not only older but also biologically distinct from younger AML
      patients, particularly in terms of the high incidence of poor prognostic
      karyotypes and resistance to therapy.

PMID- 12792699
TI  - Association studies between -1185A/G von Willebrand factor gene polymorphism and
      coronary artery disease.
AB  - High levels of von Willebrand factor (vWF) have been associated with
      cardiovascular disease. The A allele of the -1185A/G polymorphism in the 5'
      regulatory region of the vWF gene was associated with the highest plasma vWF
      levels in a normal population. To examine the association between -1185A/G
      polymorphism and coronary artery disease (CAD), 173 Brazilian Caucasian subjects
      submitted to coronary angiography were studied. Of these, 57 (33%) had normal
      coronary arteries (control group) and 116 (67%) had CAD (patient group). Plasma
      vWF levels were higher in patients (145 U/dl) than in controls (130 U/dl), but
      the differences were significant only for O blood group subjects. Polymerase
      chain reaction amplification of the 864-bp vWF promoter region followed by AccII
      restriction digestion was used to identify the -1185A/G genotypes. The -1185A
      allele frequency was 43.1% in patients and 44.7% in controls. Allele and genotype
      frequencies were not significantly different between patients and controls. No
      association was observed between the -1185A/G genotypes and plasma vWF levels in
      patients or controls. These results suggest that -1185A/G polymorphism is not an
      independent risk factor for CAD.

PMID- 12792700
TI  - Usefulness of a rapid immunometric assay for intraoperative parathyroid hormone
      measurements.
AB  - Intraoperative parathyroid hormone (IO-PTH) measurements have been proposed to
      improve operative success rates in primary, secondary and tertiary
      hyperparathyroidism (PHP, SHP and THP). Thirty-one patients requiring
      parathyroidectomy were evaluated retrospectively from June 2000 to January 2002.
      Sixteen had PHP, 7 SHP and 8 THP. Serum samples were taken at times 0 (before
      resection), 10, 20 and 30 min after resection of each abnormal parathyroid gland.
      Samples from 28 patients were frozen at -70 C for subsequent tests, whereas
      samples from three patients were tested while surgery was being performed. IO-PTH
      was measured using the Elecsys immunochemiluminometric assay (Roche, Mannheim,
      Germany). The time necessary to perform the assay was 9 min. All samples had a
      second measurement taken by a conventional immunofluorimetric method. We
      considered as cured patients who presented normocalcemia in PHP and THP, and
      normal levels of PTH in SHP one month after surgery and who remained in this
      condition throughout the follow-up of 1 to 20 months. When rapid PTH assay was
      compared with a routine immunofluorimetric assay, excellent correlation was
      observed (r = 0.959, P < 0.0001). IO-PTH measurement showed a rapid average
      decline of 78.8% in PTH 10 min after adenoma resection in PHP and all patients
      were cured. SHP patients had an average IO-PTH decrease of 89% 30 min after total
      parathyroidectomy and cure was observed in 85.7%. THP showed an average IO-PTH
      decrease of 91.9%, and cure was obtained in 87.5% of patients. IO-PTH can be a
      useful tool that might improve the rate of successful treatment of PHP, SHP and
      THP.

PMID- 12792701
TI  - A randomized double-blind study of the short-time treatment of obese patients
      with nonalcoholic fatty liver disease with ursodeoxycholic acid.
AB  - In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty
      liver disease, 30 patients with body mass indices higher than 25, serum levels of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma
      glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of
      normality, and hepatic steatosis demonstrated by ultrasonography were randomized
      into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1
      ursodeoxycholic acid for three months. Abdominal computed tomography was
      performed to quantify hepatic fat content, which was significantly correlated
      with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass
      index remained stable for both groups throughout the study, but a significant
      reduction in mean ( +/- SEM) serum levels of ALT, AST and gamma-GT was observed
      only in the treated group (ALT = 81.2 +/- 9.7, 44.8 +/- 7.7, 48.1 +/- 7.7 and
      52.2 +/- 6.3 IU/l at the beginning and after the first, second and third months,
      respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 +/-
      9.8, 54.5 +/- 7, 60 +/- 7.6 and 43.7 5 IU/l, respectively. No alterations in
      hepatic lipid content were observed in these patients by computed tomography
      examination (50.2 +/- 4.2 Hounsfield units (HU) at the beginning versus 51.1 +/-
      4.1 HU at the third month). These results show that ursodeoxycholic acid is able
      to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty
      liver disease, but this effect is not related to modifications in liver fat
      content.

PMID- 12792702
TI  - The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated
      hemoglobin on the hemoglobin-oxygen affinity of diabetic patients.
AB  - The position of the oxygen dissociation curve (ODC) is modulated by 2,3
      diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red
      cell shift the curve to the left, whereas increases in concentration cause a
      shift to the right of the ODC. Some earlier studies on diabetic patients have
      reported that insulin treatment may reduce the red cell concentrations of 2,3
      DPG, causing a shift of the ODC to the left, but the reports are contradictory.
      Three groups were compared in the present study: 1) nondiabetic control
      individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on
      insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM)
      patients using oral hypoglycemic agents and no insulin treatment (N = 22). The
      overall position of the ODC was the same for the three groups despite an increase
      of the glycosylated hemoglobin fraction that was expected to shift the ODC to the
      left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%;
      NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin
      fraction on the position of the ODC appeared to be counterbalanced by small
      though statistically significant increases in 2,3-DPG concentration from 2.05
      (control) to 2.45  mol/ml blood (IDDM). Though not statistically significant, an
      increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels
      were the same for all groups. The positions of the ODC were the same for control
      subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen
      saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM,
      respectively. In conclusion, our data question the idea of adverse side effects
      of insulin treatment on oxygen transport. In other words, the shift to the left
      reported by others to be caused by insulin treatment was not detected.

PMID- 12792703
TI  - Lack of evidence for the pathogenic role of iron and HFE gene mutations in
      Brazilian patients with nonalcoholic steatohepatitis.
AB  - The hypothesis of the role of iron overload associated with HFE gene mutations in
      the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent
      years. In the present study, biochemical and histopathological evidence of iron
      overload and HFE mutations was investigated in NASH patients. Thirty-two NASH
      patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and
      12% Asians, were submitted to serum aminotransferase and iron profile
      determinations. Liver biopsies were analyzed for necroinflammatory activity,
      architectural damage and iron deposition. In 31 of the patients, C282Y and H63D
      mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased
      in 30 patients, 2.42   1.12 times the upper normal limit on average. Serum iron
      concentration, transferrin saturation and ferritin averages were 99.4   31.3
      g/dl, 33.1   12.7% and 219.8   163.8  g/dl, respectively, corresponding to normal
      values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in
      three patients and was not associated with architectural damage (P = 0.53) or
      with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31)
      found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible
      with those described for the local population. In conclusion, no evidence of an
      association of hepatic iron overload and HFE mutations with NASH was found.
      Brazilian NASH patients comprise a heterogeneous group with many associated
      conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs,
      but not hepatic iron overload, and their disease susceptibility could be related
      to genetic and environmental features other than HFE mutations.

PMID- 12792704
TI  - Functional dyspepsia: relationship between clinical subgroups and Helicobacter
      pylori status in Western Turkey.
AB  - The etiology of functional dyspepsia is not known. The objective of the present
      study was to determine the characteristics of functional dyspepsia in Western
      Turkey. We divided 900 patients with functional dyspepsia into three subgroups
      according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML),
      281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients
      were submitted to endoscopic evaluation, with two biopsies taken from the cardia
      and corpus, and four from the antrum of the stomach. All biopsy samples were
      studied for Helicobacter pylori (Hp) density, chronic inflammation, activity,
      intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by
      histological examination. One antral biopsy was used for the rapid urease test.
      Tissue cagA status was determined by PCR from an antral biopsy specimen by a
      random sampling method. We also determined the serum levels of tumor necrosis
      factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed
      statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and
      cagA positivity was significantly higher in the UL subgroup than in the others.
      The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp
      density. The ML subgroup also showed the lowest level of Hp-induced inflammation
      among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any
      difference between groups. Our findings show a poor association of Hp with the ML
      subgroup of functional dyspepsia, but a stronger association with the UL and C
      subgroups.

PMID- 12792705
TI  - Dietary fiber, energy intake and nutritional status during the treatment of
      children with chronic constipation.
AB  - The present prospective study was carried out to determine dietary fiber and
      energy intake and nutritional status of children during the treatment of chronic
      constipation. Twenty-five patients aged 2 to 12 years with chronic constipation
      were submitted to clinical evaluation, assessment of dietary patterns, and
      anthropometry before and after 45 and 90 days of treatment. The treatment of
      chronic constipation included rectal disimpaction, ingestion of mineral oil and
      diet therapy. The standardized diet prescribed consisted of regular food without
      a fiber supplement and met the nutrient requirements according to the recommended
      daily allowance. The fiber content was 9.0 to 11.9 g for patients aged less than
      6 years and 12.0 to 18.0 g for patients older than 6 years. Sixteen patients
      completed the 90-day follow-up and all presented clinical improvement. The
      anthropometric variables did not change, except midarm circumference and triceps
      skinfold thickness which were significantly increased. Statistically significant
      increases were also found in percent calorie intake adequacy in terms of
      recommended daily allowance (55.5 to 76.5% on day 45 and to 68.5% on day 90; P =
      0.047). Percent adequacy of minimum recommended daily intake of dietary fiber
      (age + 5 g) increased during treatment (from 46.8 to 52.8% on day 45 and to 56.3%
      on day 90; P = 0.009). Food and dietary fiber intake and triceps skinfold
      thickness increased during follow-up. We conclude that the therapeutic program
      provided a good clinical outcome.

PMID- 12792706
TI  - Weight of preterm newborns during the first twelve weeks of life.
AB  - A longitudinal and prospective study was carried out at two state-operated
      maternity hospitals in Belo Horizonte during 1996 in order to assess the weight
      of preterm appropriate-for-gestational-age newborns during the first twelve weeks
      of life. Two hundred and sixty appropriate-for-gestational-age preterm infants
      with birth weight <2500 g were evaluated weekly. The infants were divided into
      groups based on birth weight at 250-g intervals. Using weight means, somatic
      growth curves were constructed and adjusted to Count's model. Absolute (g/day)
      and relative (g kg-1 day-1) velocity curves were obtained from a derivative of
      this model. The growth curve was characterized by weight loss during the 1st week
      (4-6 days) ranging from 5.9 to 13.3% (the greater the percentage, the lower the
      birth weight), recovery of birth weight within 17 and 21 days, and increasingly
      higher rates of weight gain after the 3rd week. These rates were proportional to
      birth weight when expressed as g/day (the lowest and the highest birth weight
      neonates gained 15.9 and 30.1 g/day, respectively). However, if expressed as g kg
      1 day-1, the rates were inversely proportional to birth weight (during the 3rd
      week, the lowest and the highest weight newborns gained 18.0 and 11.5 g kg-1 day
      1, respectively). During the 12th week the rates were similar for all groups (7.5
      to 10.2 g kg-1 day-1). The relative velocity accurately reflects weight gain of
      preterm infants who are appropriate for gestational age and, in the present
      study, it was inversely proportional to birth weight, with a peak during the 3rd
      week of life, and a homogeneous behavior during the 12th week for all weight
      groups.

PMID- 12792707
TI  - Antagonism of the acute hemodynamic effects of captopril in decompensated
      congestive heart failure by aspirin administration.
AB  - The concomitant use of angiotensin-converting enzyme inhibitors and aspirin may
      cause pharmacological antagonism. Hence we examined the effect of aspirin on the
      neurohormonal function and hemodynamic response to captopril in heart failure
      patients. Between April 1999 and August 2000, 40 patients were randomized into
      four equal groups: 1) captopril, 2) aspirin, 3) captopril-aspirin: captopril was
      given alone on the first day, followed by aspirin on the remaining days, and 4)
      aspirin-captopril: aspirin was given alone on the first day, followed by
      captopril on the remaining days. Hemodynamic, norepinephrine and prostaglandin
      measurements were performed pre- and post-medication for 4 days. Captopril (50
      mg) was given orally every 8 h and 300 mg aspirin was given on the first day, and
      100 mg/day thereafter. In the captopril group and only on the first day of
      captopril-aspirin, captopril produced increases in cardiac index (2.1 +/- 0.6 to
      2.5 +/- 0.5 l min-1 m-2, P<0.0001), and reduced peripheral vascular resistance
      (1980 +/- 580 to 1545 +/- 506 dyn s-1 cm-5/m , P<0.0001) and pulmonary wedge
      pressure (20 +/- 4 to 15 +/- 4 mmHg, P<0.0001). In contrast, aspirin alone or
      associated with captopril showed no significant hemodynamic changes.
      Norepinephrine decreased (P<0.02) only in the captopril group. Prostaglandin
      levels did not differ significantly among groups. Thus, aspirin compromises the
      short-term hemodynamic and neurohormonal effects of captopril in patients with
      acute decompensated heart failure.

PMID- 12792708
TI  - Functional changes of human quadriceps muscle injured by eccentric exercise.
AB  - The present study evaluated functional changes of quadriceps muscle after injury
      induced by eccentric exercise. Maximal isometric torque of quadriceps and the
      surface electromyography (root mean square, RMS, and median frequency, MDF) of
      the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined
      before, immediately after and during the first 7 days after injury. Serum
      creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to
      identify muscle injury. The subject was used as her own control and percent
      refers to pre-injury data. Experiments were carried out with a sedentary 23-year
      old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric
      contractions (angular velocity of 5 /s; range of motion from 40  to 110  of knee
      flexion). The isometric torque of the quadriceps (knee at 90  flexion) decreased
      52% immediately after eccentric exercise and recovered on the 5th day. The
      highest reduction of RMS occurred on the 2nd day after injury in both VL (63%)
      and VMO (66%) and only VL recovered to the pre-injury level on the 7th day.
      Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL,
      respectively) and recovered one day later. Serum CK levels increased by 109% on
      the 2nd day and were still increased by 32% on the 7th day. MRI showed large
      areas of injury especially in the deep region of quadriceps. In conclusion,
      eccentric exercise decreased the isometric torque and electromyographic signals
      of quadriceps muscle, which were recovered in one week, despite the muscle
      regeneration signals.

PMID- 12792709
TI  - Prevalence of Y chromosome deletions in a Brazilian population of nonobstructive
      azoospermic and severely oligozoospermic men.
AB  - We determined the prevalence of Y chromosome deletions in a population of 60
      Brazilian nonobstructive azoospermic and severely oligozoospermic men. PCR-based
      screening of microdeletions was performed on lymphocyte DNA for the presence of
      14 sequence-tagged sites (STS) located in the azoospermic factor (AZF) on the Yq
      chromosome. All STS were amplified efficiently in samples from 12 fertile men
      tested, but failed to be amplified in samples from fertile women, indicating the
      specificity of PCR conditions for Yq screening. Overall, 4 of the 60 infertile
      patients tested (6.7%) exhibited deletion of the Y chromosome, 2 of them being
      severely oligozoospermic patients (P10 and P32) and 2 azoospermic men (patients
      P47 and P57). Patients P47 and P57 presented larger deletions in the AZFa, AZFb
      and AZFc subregions, with apparent loss of Yq material evidenced by karyotype
      analysis. Patients P10 and P32 presented deletions confined to the AZFc region,
      involving the DAZ locus. Male relatives of patients P10 and P32 had no Y
      chromosome deletions and presented a normal karyotype, suggesting a de novo
      status of the deletions found. Our data add to the growing literature showing
      that microdeletions of the Y chromosome can be the cause of male idiopathic
      infertility.

PMID- 12792710
TI  - Lymphocyte subpopulations during cytomegalovirus disease in renal transplant
      recipients.
AB  - We have determined the number of circulating T, B and natural killer cells in
      renal transplant recipients in order to detect changes during cytomegalovirus
      (CMV) infections. Serial blood samples were taken from 61 patients on standard
      triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone).
      Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+,
      CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Forty-eight patients
      (78.7%) developed active CMV infection, and all of them subsequently recovered.
      Twenty of the infected patients (32.8%) presented symptoms compatible with CMV
      disease during the infectious process. The number of lymphocytes and their main
      subpopulations were normal before the onset of CMV disease. During the disease
      there was a decrease followed by a significant increase (P<0.005) in the number
      of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed
      in natural killer cells or B lymphocytes during the disease. We conclude, as
      observed in all viremic patients recovering from infection, that recovery is
      associated with an increase in the number of T cell subsets. The monitoring of
      different lymphocyte subsets along with antigenemia can be extremely useful in
      the detection of patients at high risk of developing CMV symptoms, allowing the
      early introduction of antiviral therapy or the reduction of immunosuppression
      therapy.

PMID- 12792711
TI  - Factors associated with penicillin-nonsusceptible pneumococcal infections in
      Brazil.
AB  - Resistance of Streptococcus pneumoniae is a worldwide, growing problem. Studies
      of factors associated with resistance to penicillin have not been conducted in
      Brazil. The objective of the present study was to evaluate factors associated
      with infection by S. pneumoniae not susceptible to penicillin. A prevalence study
      was conducted including all patients with a positive culture for S. pneumoniae in
      a hospital from July 1991 to December 1992 and the year 1994. Of 165 patients
      identified, 139 were considered to have clinically relevant infections and 88% of
      them had invasive infections. All infections were community acquired and
      consisted of pneumonia (44%) and of central nervous system (19%), pelvic or
      abdominal (12%), upper airway or ocular (12%), primary bloodstream (9%) and skin
      and soft tissue (5%) infections. Mortality was 25%. Susceptibility to penicillin
      was present in 77.6% of the isolates; 21.8% were relatively resistant, and one
      isolate was resistant (minimal inhibitory concentration = 4 micro g/ml).
      Multivariate analysis showed that age below 4 years (odds ratio (OR): 3.53, 95%
      confidence interval (95%CI): 1.39-8.96) and renal failure (OR: 5.50, 95%CI: 1.07
      28.36) were associated with lack of susceptibility to penicillin. Bacteremia
      occurred significantly less frequently in penicillin-nonsusceptible infections
      (OR: 0.34, 95%CI: 0.14-0.84), possibly suggesting that lack of penicillin
      susceptibility is associated with lower virulence in S. pneumoniae.

PMID- 12792712
TI  - Autonomic nervous system dysfunction in children with severe tetanus:
      dissociation of cardiac and vascular sympathetic control.
AB  - The medical records of ten pediatric patients with a clinical diagnosis of
      tetanus were reviewed retrospectively. The heart rate and blood pressure of all
      tetanus patients were measured noninvasively every hour during the first two
      weeks of hospitalization. Six of ten tetanus patients presented clinical evidence
      of sympathetic hyperactivity (group A) and were compared with a control group
      consisting of four children who required mechanical ventilation for diseases
      other than tetanus (group B). Heart rate and blood pressure simultaneously and
      progressively increased to a maximum by day 7. The increase over baseline was
      43.70 +/- 11.77 bpm (mean +/- SD) for heart rate (P<0.01) and 38.60 +/- 26.40
      mmHg for blood pressure (P<0.01). These values were higher and significantly
      different from those of the control group (group B) at day 6, which had an
      average heart rate increase over baseline of 19.35 +/- 12.26 bpm (P<0.05) and
      blood pressure of 10.24 +/- 13.30 mmHg (P<0.05). By the end of the second week of
      hospitalization, in group A the increase of systolic blood pressure over baseline
      had diminished to 9.60 +/- 15.37 mmHg (P<0.05), but the heart rate continued to
      be elevated (27.80 +/- 33.92 bpm, P = NS), when compared to day 7 maximal values.
      The dissociation of these two cardiovascular variables at the end of the second
      week of hospitalization suggests the presence of asymmetric cardiac and vascular
      sympathetic control. One possible explanation for these observations is a
      selective and delayed action of tetanus toxin on the inhibitory neurons which
      control sympathetic outflow to the heart.

PMID- 12792713
TI  - Regional myocardial function in healthy adults: assessment through tissue Doppler
      echocardiography.
AB  - OBJECTIVE: To characterize left ventricular regional myocardial function through
      tissue Doppler echocardiography in healthy adults and to assess the influence of
      aging in this function. METHODS: In 45 healthy volunteers divided in two groups
      (< 45 and > 45 years old) we assessed longitudinal and radial regional function
      (velocities, times intervals and velocity-time integrals). Data were compared in
      each group and between groups. RESULTS: Systolic function: a). longitudinal:
      higher velocities and integrals in lateral and inferior walls and in basal
      segments, with a trend to reduction of these parameters with aging; b). radial:
      higher basal velocities, no significant change with aging. Diastolic function:
      a). longitudinal: higher velocities in lateral and inferior walls and in basal
      segments. With aging e and e/a velocities and integrals decreased, a increased
      and older individuals showed lower percentage of segments with e/a >1; b).
      radial: aging was associated with lower e and higher a velocities. CONCLUSION:
      1). Tissue Doppler echocardiography detects physiological differences between
      regional myocardial function of different ventricular segments, in velocities,
      times intervals and integrals, with physiological heterogeneity and asynchrony;
      2). Many of these data are age dependent; 3). Our data contribute to define
      normal values, and may become useful when compared with data from populations
      with heart diseases.

PMID- 12792714
TI  - Effect of arginine vasopressin on the canine epicardial coronary artery:
      experiments on V1-receptor-mediated production of nitric oxide.
AB  - OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived
      nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied
      segments of canine left circumflex coronary arteries suspended in organ chambers
      to measure isometric force. The coronary artery segments were contracted with
      prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine
      vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M).
      RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced
      transient, but significant (p<0.05), relaxation in arterial segments with
      endothelium, and an increase, not significant, in tension in arteries without
      endothelium. Endothelium-dependent relaxation to arginine vasopressin was
      inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L
      NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous
      L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of
      L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation
      to vasopressin was also reversibly inhibited by the vasopressin V1-receptor
      blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION:
      Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide
      release from L-arginine.

PMID- 12792715
TI  - Surgical myocardial revascularization without extracorporeal circulation.
AB  - OBJECTIVE: To assess the immediate postoperative period of patients undergoing
      myocardial revascularization without extracorporeal circulation with different
      types of grafts. METHODS: One hundred and twelve patients, 89 (79.5%) of whom
      were males, were revascularized without extracorporeal circulation. Their ages
      ranged from 39 to 85 years. The criteria for indicating myocardial
      revascularization without extracorporeal circulation were as follows:
      revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial
      trajectory on coronary angiography, noncalcified coronary arteries, and tolerance
      of the heart to the different rotation maneuvers. RESULTS: Myocardial
      revascularization without extracorporeal circulation was performed in 112
      patients. Three were converted to extracorporeal circulation, which required a
      longer hospital stay but did not impact mortality. During the procedure, the
      following events were observed: atrial fibrillation in 10 patients, ventricular
      fibrillation in 4, total transient atrioventricular block in 2, ventricular
      extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood
      transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography
      was performed in 20 patients on the seventh postoperative day when the grafts
      were patent. CONCLUSION: Myocardial revascularization without extracorporeal
      circulation is a reproducible technique that is an alternative for treating
      ischemic heart disease.

PMID- 12792716
TI  - Subendocardial fibrosis in remote myocardium results from reduction of coronary
      driving pressure during acute infarction in rats.
AB  - OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute
      MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat
      model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)]
      were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10
      minutes before and after coronary artery ligature. Collagen volume fraction (CVF)
      was calculated in picrosirius red-stained heart tissue sections 4 weeks later.
      RESULTS: Before surgery, all hemodynamic variables were comparable among groups.
      After surgery, LV end-diastolic pressure increased and coronary driving pressure
      decreased significantly in the LMI compared with the sham group. LV dP/dt max and
      dP/dt min of both the SMI and LMI groups were statistically different from those
      of the sham group. CVF within non-MI interventricular septum and right ventricle
      did not differ between each MI group and the sham group. Otherwise,
      subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF
      correlated negatively with post-MI systemic blood pressure and coronary driving
      pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis
      identified post-MI coronary driving pressure as an independent predictor of SE
      CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE
      collagen deposition in non-MI and results from a reduction in myocardial
      perfusion pressure occurring early on in the setting of MI.

PMID- 12792717
TI  - New auxiliary indicators for the differential diagnosis of functional
      cardiorespiratory limitation in patients with chronic obstructive pulmonary
      disease and congestive heart failure.
AB  - OBJECTIVE: To differentiate the nature of functional cardiorespiratory
      limitations during exercise in individuals with chronic obstructive pulmonary
      disease (COPD) or congestive heart failure (CHF) and to determine indicators that
      may help their classifications. METHODS: The study comprised 40 patients: 23 with
      COPD and 17 with CHF. All individuals underwent maximal cardiopulmonary exercise
      testing on a treadmill. RESULTS: The values of peak gas exchange ratio (R peak),
      peak carbon dioxide production (VCO2 peak), and peak oxygen ventilatory
      equivalent (V E O2 peak) were higher in the patients with CHF than in those with
      COPD, and, therefore, those were the variables that characterized the differences
      between the groups. For group classification, the differentiating functions with
      the R peak, VCO2 peak (L/min), and V E O2 peak variables were used as follows:
      group COPD: - 44.886 + 78.832 x R peak + 5.442 x VCO2 peak + 0.336 x V (E) O(2)
      peak; group CHF: - 69.251 + 89.740 x R peak + 8.461 x VCO2 peak + 0.574 x V (E)
      O(2) peak. The differentiating function, whose result is greater, correctly
      classifies the patient's group as 90%. CONCLUSION: The R peak, VCO(2) peak, and
      V(E) O(2) peak values may be used to identify the cause of the functional
      cardiorespiratory limitations in patients with COPD and CHF.

PMID- 12792718
TI  - Predictive factors of complications after coronary stent implantation.
AB  - OBJECTIVE: To analyze the predictive factors of complications after implantation
      of coronary stents in a consecutive cohort study. METHODS: Clinical and
      angiographic characteristics related to the procedure were analyzed, and the
      incidence of major cardiovascular complications (myocardial infarction, urgent
      surgery, new angioplasty, death) in the in-hospital phase were recorded. Data
      were stored in an Access database and analyzed by using the SPSS 6.0 statistical
      program and a stepwise backwards multiple logistic regression model. RESULTS: One
      thousand eighteen (mean age of 61 +/-11 years, 29% females) patients underwent
      1070 stent implantations. The rate of angiographic success was 96.8%, the rate of
      clinical success was 91%, and the incidence of major cardiovascular complications
      was 7.9%. The variables independently associated with major cardiovascular
      complications, with their respective odds ratio (OR) were: rescue stent, OR = 5.1
      (2.7-9.6); filamentary stent, OR = 4.5 (2.2-9.1); first-generation tubular stent,
      OR = 2.4 (1.2-4.6); multiple stents, OR = 3 (1.6-5.6); complexity of the lesion,
      OR = 2.4 (1.1-5.1); thrombus, OR = 2 (1.1-3.5). CONCLUSION: The results stress
      the importance of angiographic variables and techniques in the risk of
      complications and draw attention to the influence of the stent's design on the
      result of the procedure.

PMID- 12792719
TI  - Effect of oscillatory breathing on the variability of the RR Intervals and its
      prognostic importance in individuals with left ventricular global systolic
      dysfunction.
AB  - OBJECTIVE: To assess the effect of the oscillatory breathing on the variability
      of RR intervals (VRR) and on prognostic significance after one year follow-up in
      subjects with left ventricular global systolic dysfunction. METHODS: We studied
      76 subjects, whose age ranged from 40 to 80 years, paired for age and gender,
      divided into two groups: group I - 34 healthy subjects; group II - 42 subjects
      with left ventricular global systolic dysfunction (ejection fraction < or =
      0.40). The ECG signals were acquired during 600s in supine position, and analyzed
      the variation of the thoracic amplitude and the VRR. Clinical and V-RR variables
      were applied into a logistic multivariate model to foretell survival after one
      year follow-up. RESULTS: Oscillatory breathing was detected in 35.7% of subjects
      in vigil state of group II, with a concentration of the spectral power in the
      very low frequency band, and was independent of the presence of diabetes,
      functional class, ejection fraction, cause of ventricular dysfunction and
      survival after one year follow-up. In the logistic regression model, ejection
      fraction was the only independent variable to predict survival. CONCLUSION: 1).
      Oscillatory breathing pattern is frequent during wakefulness in the left
      ventricular global systolic dysfunction and concentrates spectral power in the
      very low band of V-RR; 2). it does not relate to severity and cause of left
      ventricular dysfunction; 3). ejection fraction is the only independent predictive
      variable for survival in this group of subjects.

PMID- 12792720
TI  - Dual anterior descending coronary artery associated with coronary artery disease.
AB  - The patient is a male with risk factors for coronary artery disease, who was
      referred for cardiac catheterization after acute myocardial infarction in the
      inferior wall. The patient underwent transluminal coronary angioplasty in the
      right coronary artery with successful stent implantation.

PMID- 12792721
TI  - [Case 5 - Instituto do Coracao do Hospital das Clinicas da FMUSP].

PMID- 12792722
TI  - [Genetic changes and cholesterolemia: new Brazilian studies].

PMID- 12792723
TI  - [Standardization of equipment and techniques to the use of electrocardiography
      and high-resolution electrocardiography exams].

PMID- 12792724
TI  - Evaluating prostate cancer cell culturing methods: a comparison of cell
      morphologies and metabolic activity.
AB  - LNCaP prostate cancer cells were grown under four unique cultivation conditions.
      Two types of bioreactor systems were used to observe the influence of low-shear
      culture conditions allowing for three-dimensional growth: a) a perfusion rotating
      wall vessel (RWV) bioreactor; and b) a high aspect ratio vessel (HARV) RWV
      bioreactor, with periodic medium exchanges (fed-batch). In addition, two growth
      methods utilized tissue culture flasks (TCFs): a) unaltered or conventional TCFs;
      and b) poly(2-hydroxyethyl methacrylate) [poly(HEMA)] coated TCFs, to inhibit
      cell attachment. Comparisons were drawn based on qualitative observation of cell
      morphology and quantitative metabolic data. Similar cellular metabolism was
      demonstrated for cells grown under each condition. The degree of aggregation,
      however, varies considerably. Spherical shaped aggregates with diameters of 1 to
      3 mm were produced when cells were grown within the perfusion-RWV bioreactor. All
      other growth conditions produced irregular shaped aggregates of various sizes.
      Quantitative results demonstrated the expected glucose utilization concomitant
      with lactate accumulation. Immunohistochemical evaluations were unremarkable for
      all four cultivation conditions. Results demonstrate that use of the perfusion
      RWV bioreactor is advantageous in obtaining spherical aggregates, while grown in
      a controlled environment.

PMID- 12792725
TI  - Immunohistochemical analysis of estrone sulfatase and aromatase in human breast
      cancer tissues.
AB  - We examined, by immunohistochemical analysis, the expression of aromatase and
      estrone sulfatase (E1-STS) which are the two major enzymes involved in in situ
      estrogen synthesis in breast cancer tissue. In the 83 cases examined, E1-STS,
      which hydrolyses estrone sulfate (E1S) to estrone (E1), was dominantly detected
      in tumor cells in 43 (59.0%) cases. Aromatase, which converts androgens to
      estrogens, was dominantly detected in stromal cells of the tumor. It was detected
      in 39 (47.0%) of the 83 cases. There was no significant correlation between the
      expression of these two enzymes and clinicopathological factors. We found a
      tendency for a correlation between aromatase expression and E1-STS expression in
      breast tumor (p=0.075). In terms of the possible use of these enzymes as
      prognostic indicators, patients who had aromatase in their tumor showed longer
      relapse-free survival than those lacking aromatase (p=0.045). Significant
      correlations between the expression of aromatase and the angiogenesis regulators,
      vascular endothelial growth factor and thymidine phosphorylase, were found
      (p=0.047 and p=0.046, respectively), though the presence of aromatase did not
      correlate with intratumoral microvessel density. This may indicate that aromatase
      is involved in vascular permeability and recruitment of endothelial cells rather
      than neovascularization. It may be useful to study the expression of aromatase
      and E1-STS using immunocytochemical analysis for understanding the tumor
      characteristics in breast cancer.

PMID- 12792726
TI  - Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal
      stromal tumor of the stomach.
AB  - Hypoxia inducible factor (HIF)-1 is reported to transactivate expression of
      vascular endothelial growth factor (VEGF), which is an important angiogenic
      factor. The aim of this study was to elucidate the clinical significance of HIF
      1alpha expression in gastrointestinal stromal tumors (GIST). Specimens obtained
      from 53 patients who underwent surgical resection for GIST of the stomach were
      used in this study. Specimens were examined immunohistochemically for HIF-1alpha,
      VEGF, and Ki-67 expression. Tumor microvessel density (MVD) was determined
      immunohistochemically with anti-CD31 antibody and was estimated by averaging the
      counts from three high-power fields in the area showing the greatest
      neovascularization. HIF-1alpha expression was detected in 17 (32.1%) of 53
      lesions and was correlated significantly with tumor size, liver metastasis, VEGF
      expression, and MVD. Prognosis was significantly poorer in patients with tumors
      expressing HIF-1alpha than in patients with tumors lacking HIF-1alpha expression.
      HIF-1alpha may play a role in angiogenesis and tumor progression of GIST through
      regulation of VEGF.

PMID- 12792727
TI  - Prognostic factors in the so-called malignant mesenchymoma: a clinicopathological
      and immunohistochemical analysis.
AB  - The term "malignant mesenchymoma" (MM) has traditionally been applied to a group
      of malignant soft tissue tumors that are characterized by the presence of two or
      more different mesenchymal tissue components in the same neoplasm. Currently,
      sarcomas with multilineage differentiation fulfilling the criteria of MM tend to
      be diagnosed as specific sarcomas with heterologous differentiation (e.g., de
      differentiated liposarcoma) rather than MM; however, some cases of these tumors
      are difficult to classify. The purpose of this study was to analyze the
      clinicopathological and immunohistochemical features of these unclassifiable
      tumors, the so-called MM, and to determine whether some parameters are a useful
      adjunct for the classification of these tumors from the viewpoint of clinical
      outcome. Twelve cases of so-called MM were investigated retrospectively. The
      patients (six male, six female) ranged in age from 6 to 71 years (mean 48 years).
      Tumor size ranged from 3 to 20 cm (mean 13 cm). Tumor locations included the
      retroperitoneum (five cases), abdominal wall (two), thigh (two), forearm (one),
      lung (one), and parotid gland (one). The differentiated mesenchymal components
      were rhabdomyosarcomatous (RMS) (six cases), liposarcomatous (five),
      chondrosarcomatous (five), osteosarcomatous (five), or leiomyosarcomatous (four).
      Follow-up in all cases (range 4-129 months; mean 36 months) showed a 67% local
      recurrence rate, a 33% metastatic rate, and a 50% disease-related mortality. The
      patients who were under 40 years of age or who had an RMS component showed
      significantly worse survival than did patients in the other groups. The other
      mesenchymal components showed no significant correlation with survival. The
      immunophenotypes of p53 and mdm2 were almost identical between the two
      mesenchymal components in each case; however, there was no significant
      correlation between either of these immunophenotypes and the clinical outcome.
      None of the other factors (gender, tumor site, tumor size, or MIB-1-labeling
      index) was found to be a statistically significant prognostic indicator. In
      conclusion, a patient age under 40 years and the presence of an RMS component
      appear to be poor prognostic indicators of survival in patients with so-called
      MM, and to be a useful adjunct for the classification of these tumors.

PMID- 12792728
TI  - The elevated serum interleukin-6 correlates with the increased serum butyrate
      level in patients with nasopharyngeal carcinoma.
AB  - We investigated the clinical significance and regulation of serum interleukin-6
      (IL-6) in patients with nasopharyngeal carcinoma (NPC). Serum IL-6 levels of 314
      NPC patients and 202 healthy individuals were determined. Of the NPC patients,
      69.1% (217/314) showed higher IL-6 levels than that of normal average (2.76+/
      2.06 pg/ml). Elevation of IL-6 correlated with the advanced disease and the
      adverse prognosis of NPC patients. By employing in situ hybridization technique,
      IL-6 mRNA was detected in the tumor cells of NPC patients with high serum IL-6
      levels. Concurrently, serum levels of butyrate were determined in 147 NPC
      patients and 52 healthy individuals by gas chromatography. Patients with elevated
      serum butyrate concentrations (4.2+/-2.2 micro M) also had significantly higher
      IL-6 levels (29.14+/-5.17 pg/ml). No detectable serum butyrate was measured in
      the healthy individuals. In order to investigate the direct relationship between
      butyrate and IL-6, n-sodium butyrate (n-BT) was added to the NPC cells in an in
      vitro study, and marked increase of IL-6 expression was detected in n-BT-treated
      cells. Our results suggested that tumor cells could be an important source of
      elevated serum IL-6 in patients with NPC and that IL-6 level in NPC patients was
      proportional to the serum butyrate concentration. In vitro, IL-6 expression in
      NPC cells could be up-regulated by butyrate.

PMID- 12792729
TI  - Clinical experience of ureteroscopic treatment for ureteral transitional cell
      carcinoma using the Holmium:YAG laser.
AB  - The standard operative method for ureteral transitional cell carcinoma is
      nephrouterectomy with partial bladder excision of the ureteral orifice of the
      affected bladder. However, a conservative kidney operation and endoscopy are now
      being performed for low grade, low stage cases. We performed an operation using a
      Holmium: YAG laser, and examined its safety and efficacy. The patients were four
      men, and 1 woman aged from 68 to 87 (mean 78) years. There were 2 imperative
      cases (1 solitary kidney case, and 1 high-risk case), and 3 elective cases. The
      tumor size ranged from 8 to 25 (mean 14) mm. Urinary cytology was negative in all
      cases, and the tumors were pathologically diagnosed as grade 1 atypism on biopsy.
      A VersaPulse Select 80 laser generator, a 365 micro m SlimLine laser fiber, and
      an 8F rigid ureteroscope were used. A 6F double J catheter was indwelt for three
      weeks after the surgery. The pulse energy setting was 0.5-1.0 J, and the
      frequency was 10 Hz. The total amount of energy was 1.02-11.22 (mean 3.56) kJ,
      and the operation time was 20-97 (mean 50) min including the time for indwelling
      a ureteral stent. Neither urinary tract perforation nor ureteral stricture caused
      by the laser irradiation were observed. The patients have been followed by
      examining urine cytology once a month, and cystoscopy, retrograde pyelography,
      and urethroscopy once every 3 months. No recurrence has been observed as of 4-20
      (mean 10) months postoperatively. Transurethral endoscopic resection using a
      Holmium: YAG laser is a safe and effective therapy for ureteral transitional cell
      carcinoma while preserving kidney and a good treatment outcome can be expected
      even in elective cases.

PMID- 12792730
TI  - Prognostic significance of p27/kip1 and apoptosis in patients with colorectal
      carcinoma.
AB  - The protein p27/kip1 is a cyclin-dependent kinase inhibitor that regulates cell
      cycle progression. In the present study, p27/kip1 expression as well as tumor
      cell proliferation and apoptosis were investigated in 80 colorectal carcinomas,
      using anti-p27/kip1 antibodies, in situ apoptosis detection kits and anti-PCNA
      antibodies. Immunohistochemical staining indicated that p27/kip1 was localized
      heterogeneously in the nuclei of cancer cells. The frequency of samples positive
      for p27/kip1 was 53.8% (43/80). There was no significant correlation between
      p27/kip1 status and clinicopathologic factors. Mean apoptotic index (AI) in
      p27/kip1-positive patients (3.22+/-1.65) was significantly higher than in
      p27/kip1-negative patients (2.46+/-1.44; p=0.033). No correlation was observed
      between p27/kip1 expression and the PCNA labeling index (PCNA-LI) (p=0.47).
      Overall survival was significantly longer for patients who were p27/kip1-positive
      (80.7%) compared to those who were negative (49.3%; p=0.0003). Univariate
      analysis revealed no significant differences between prognosis and AI or PCNA-LI.
      In multivariate analysis, p27/kip1 expression was found to be an independent
      prognostic marker (p=0.015). In conclusion, the present study shows that p27/kip1
      is a potentially important prognostic and predictive marker for outcome in
      colorectal carcinoma. These results might be explained by the role of p27/kip1 in
      promoting apoptosis.

PMID- 12792731
TI  - Prognostic significance of scoring system based on histological heterogeneity of
      invasive ductal carcinoma for node-negative breast cancer patients.
AB  - This study aimed to determine the prognostic significance of histological scoring
      system based on heterogeneity of invasive ductal carcinoma, for node-negative
      breast cancer patients. We studied 108 patients of node-negative invasive ductal
      carcinoma with invasive tumor >5 mm. Histological score of each patient was
      evaluated based on histological subtype of invasive ductal carcinoma and pattern
      of its heterogeneity. Score of each subtype was defined as follows;
      papillotubular carcinoma: score 1, solid-tubular carcinoma: score 2 and scirrhous
      carcinoma: score 3. The existence of histological heterogeneity was examined, and
      corresponding score was doubled in a pure case and scores of two dominant
      subtypes were summed in a composite case. Overall survival curves defined by
      sores were drawn by Kaplan-Meier method and the difference in survival rate was
      evaluated by log-rank test. The most significant difference of overall survival
      was recognized between low score group (scores 2, 3 and 4) and high score group
      (scores 5 and 6) (p<0.001). In addition, multivariate analysis confirmed that
      only histological score was an independent prognostic factor. These results
      suggested that assessment of histological heterogeneity of invasive ductal
      carcinoma could serve as independent potent prognostic factor for node-negative
      invasive ductal carcinoma of the breast, and this method might be useful to
      decide indication of postoperative adjuvant chemotherapy.

PMID- 12792732
TI  - Pentoxifylline inhibits leukocyte infiltration and splenocyte cytotoxicity
      against murine colon adenocarcinoma.
AB  - Pentoxifylline (PTX), a methylxanthine derivative, is commonly used in patients
      suffering from peripheral vascular diseases. Besides its well-known
      hemorheological properties PTX has been found to decrease the secretion of some
      inflammatory cytokines such as TNF, IL-12 and IFN-gamma. PTX also suppresses
      lymphocyte cytotoxicity, affecting mainly the perforin-dependent pathway. We
      investigated the influence of PTX on the splenocyte cytotoxicity and leukocyte
      infiltration in a murine colon adenocarcinoma model. We observed that PTX
      decreased the cytotoxic activity of isolated splenocytes against C-26 cells and
      reduced the inflammatory cell infiltration in the peritumoral tissue. Thus, our
      results strongly suggest the necessity of further studies concerning the safety
      of PTX use, especially in elderly patients or patients with already diagnosed
      cancer.

PMID- 12792733
TI  - Kinetics of iodide uptake and efflux in various human thyroid cancer cells by
      expressing sodium iodide symporter gene via a recombinant adenovirus.
AB  - We evaluated the potential of radioiodide therapy in human sodium iodide
      symporter (hNIS)-defective thyroid cancer cells via exogenous hNIS expression.
      Three human thyroid cancer cells (ARO, FRO and NPA) of different origin were
      transduced by a recombinant adenovirus encoding hNIS expression cassette (Rad
      hNIS). The cells were efficiently transduced by a recombinant adenovirus in a
      virus dose-dependent manner. Consequently, the hNIS protein could be readily
      detected by Western blot analysis 48-h post-infection at 10 infectious virus
      particles per cell. These hNIS-transduced cells actively transported iodide into
      the cytoplasm at the level of 11635.3, 61571.6, and 19367.5 pmoles/10(6) cells in
      ARO, FRO, and NPA, respectively. However, a significant amount of iodide was
      eluted to an iodide-free media within 60 min in all the cell lines. RT-PCR
      analysis revealed that the expression of genes related to iodide trapping (Tg,
      TSHR and TPO) was dramatically downregulated in these cells. The present study
      indicates that functional hNIS can be efficiently expressed and is responsible
      for active transport of iodide in hNIS-negative human thyroid cancer cells by a
      recombinant adenovirus. However, the human thyroid cancer cells, along with
      downregulation of iodide metabolism-related gene expression, lose the ability to
      maintain iodide. Therefore, these kinetic characteristics of iodide uptake and
      efflux may limit the therapeutic potential of hNIS/radioiodide-based treatment
      following exogenous hNIS expression in human thyroid cancer.

PMID- 12792734
TI  - Delayed methotrexate clearance in osteosarcoma patients treated with multiagent
      regimens of neoadjuvant chemotherapy.
AB  - We retrospectively studied 790 patients with osteosarcoma treated by neoadjuvant
      chemotherapy at a single institution between 1983 and 2000 according to different
      protocols, all including a high dose of methotrexate (HDMTX), to determine the
      incidence of delayed clearance of HDMTX, and identify patients at high risk for
      this kind of toxicity. Chemotherapy was administered according to 7 different
      protocols, successively activated, in which HDMTX was associated with other drugs
      (cisplatin, adriamycin, ifosfamide) in different combinations. The doses of MTX
      ranged between 7.5 to 12 g/m(2) and patients received from 1 to 10 cycles with
      MTX for a total number of 4219 cycles. The incidence of delayed clearance of MTX
      (plasma values of the drug at 24 h >5 microM/l) was 8.6% per patient and 1.6% per
      cycle of treatment. In 51 cases the delayed clearance of MTX was "mild" (plasma
      values of MTX at 24 h between 5 and 19 microM/l) and in 18 cases "severe" (plasma
      values of MTX at the 24 h >20 microM/l). The delayed clearance of MTX was
      significantly correlated with the age of patients (16% for patients over 20 vs.
      6% for younger patients: p=0.0001) and was significantly more frequent during the
      first cycles of chemotherapy (7% during the first 3 cycles of treatment vs. 2%
      during subsequent cycles). There was also a significant correlation (p=0.0001)
      between the plasma values of MTX at the end of the infusion and at 18 h and the
      delayed clearance of the drug. In addition to support treatment by increased
      hydration and sodium bicarbonate, all patients who experienced the delayed
      clearance of MTX were treated solely with a high dose of leucovorin (HDLV), which
      was started at the first 18 h. Significant neutropenia and/or thrombocythopenia,
      increase of serum creatinine, mucositis of varying degrees and vomiting occurred
      in most cases of severe delayed clearance of MTX, but all patients completely
      recovered. We conclude that in spite of adequate hydration and urine
      alkalinization and the use of pharmacokinetically guided leucoverin rescue,
      delayed clearance of MTX may still occur and that its incidence is higher in
      older patients and during the first cycles of treatment. However, if "rescue"
      treatment is started early, the consequent morbility is tolerable and these
      patients can be rescued using only HDLV, without the need for extracorporeal
      removal.

PMID- 12792735
TI  - Oncogenic pathway of sporadic colorectal cancer with novel germline missense
      mutations in the hMSH2 gene.
AB  - The deficiency of the DNA mismatch repair (MMR) system is involved in
      tumorigenesis of either familial or sporadic colorectal cancers showing
      microsatellite instability (MSI). To investigate the involvement of the mutated
      hMSH2 gene in carcinogenesis, we searched for alteration of the gene in 15 MSI
      tumors of Japanese patients with sporadic colorectal cancer by a polymerase chain
      reaction (PCR)-single strand conformation polymorphism (SSCP) and DNA sequencing
      analyses. We found 20 alterations including 7 novel mutations, 6 germline and one
      somatic. To assume an oncogenic pathway of tumor of two patients carrying
      germline missense mutations, G40S located in an evolutionarily conserved amino
      terminal motif and Y619C in a domain interacting with either hMSH3 or hMSH6,
      somatic mutations in 9 target genes of the MMR defect and in the p53 and K-ras
      genes and loss of heterozygosity (LOH) at the hMLH1 and p53 gene loci were then
      studied. In the tumor carrying G40S, other somatic hMSH2 mutations, G203R and
      687delA in the (A)(7) repeat, and 5 one-bp deletions in the target genes were
      found, while no mutation in the p53 and K-ras genes. These results indicate that
      G40S may affect the hMSH2 function and the tumor may be developed by a typical
      MSI pathway. In another tumor with Y619C, LOH at the hMLH1 gene locus, no
      mutation in MMR target genes, and two-hit inactivation of the p53 gene were
      detected. This MSI tumor seems to be developed by another than MSI pathway. These
      results indicate that there are different oncogenic pathways in the MSI sporadic
      colorectal cancers with germline missense mutations in the hMSH2 gene. We
      conclude that familial colorectal cancer-suspected cases exist in a small
      population of sporadic colorectal cancers.

PMID- 12792736
TI  - The stability of dihydropyrimidine dehydrogenase activity in colorectal cancer
      tissue after resection.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme in
      the catabolism of 5-fluorouracil (5-FU). DPD activity in tumor tissue may
      consequently serve as a predictive factor for sensitivity to 5-FU. The purpose of
      this study was to elucidate the stability of DPD activity over time in resected
      colorectal cancer tissue. DPD activity was measured in samples frozen immediately
      after the tumor was resected and in samples that had been allowed to stand at
      room temperature for 15, 30, 60, 120, and 180 min before being frozen. Surgical
      specimens obtained from 15 cases with advanced colorectal cancer were analyzed.
      The effects of differences among individuals and differences in time between
      collection and freezing were assessed by two-way analysis of variance (ANOVA).
      Significant differences in DPD activity were found among tumors (p=0.001), but
      there were no significant differences in the same tumor depending on the time
      between collection and freezing (p=0.496). Based on these results, it appears
      possible to make comparative assessments of DPD activity in colorectal cancer
      tissue without strictly stipulating the time between resection and freezing.

PMID- 12792737
TI  - Novel mutations of the cartilage oligomeric matrix protein (COMP) gene in two
      Japanese patients with pseudoachondroplasia.
AB  - Mutations in the cartilage oligomeric matrix protein (COMP) gene cause two
      skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal
      dysplasia (MED), which are autosomal dominant disorders characterized by short
      limb dwarfism. We report novel mutations of the COMP gene identified in two
      sporadic Japanese cases of PSACH. One had a novel single base substitution in
      exon 9, resulting in a missense mutation of Gly309Arg in the second type 3 repeat
      of COMP protein. The other patient had no mutations in any of the exonic
      sequences of the gene, but she did have a novel base substitution in intron 13.
      Although this mutation was not located in the conserved sequences for splicing
      donor and acceptor sites, it might disturb the precise splicing of the COMP
      transcripts, resulting in the production of abnormal protein with defective last
      type 3 repeat and/or C-terminal domain.

PMID- 12792738
TI  - Preventive effect of fermented brown rice and rice bran on diethylnitrosoamine
      and phenobarbital-induced hepatocarcinogenesis in male F344 rats.
AB  - Epidemiological and preclinical studies have suggested that nutrition plays an
      important role in the etiology of cancer. Our group previously demonstrated that
      rice germ or fermented brown rice has a preventive effect on colorectal
      carcinogenesis. The experiment described here was examined for the potential
      anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in
      male F344 rats using inhibition of diethylnitrosoamine (DEN) and phenobarbital
      (PB)-induced hepatocarcinogenesis as the measure of preventive efficacy when this
      agent was administered at 5% and 10% levels in diet during initiation phase
      (during and until 1 week after carcinogen treatment) or post-initiation phase
      (beginning 1 week after carcinogen treatment) of the carcinogenesis. Rats were
      sacrificed 20 weeks after the initiation of DEN treatment (200 mg/kg body weight,
      once weekly for 3 weeks). Expression of liver tumors was evaluated
      histopathologically. Administration of 10% FBRA in the diet during the initiation
      phase significantly decreased the incidence (43% vs. 8%) and multiplicity (0.5+/
      0.6 vs. 0.1+/-0.3) of hepatocellular carcinoma (HCC) as compared to those given
      the control diet. In addition, 5% and 10% of FBRA in the diet during post
      initiation phase significantly decreased the incidence of HCC (43% vs. 15% and
      9%, respectively) and multiplicity of hepatocellular adenoma (4.7+/-3.7 vs. 2.1+/
      2.2 and 2.4+/-1.4, respectively) and HCC (0.5+/-0.6 vs. 0.2+/-0.4 and 0.1+/-0.3,
      respectively). These data prove that FBRA has an inhibitory effect on the
      hepatocarcinogenesis in rats. FBRA could be a promising chemopreventive agent for
      human liver as well as colorectal neoplasia.

PMID- 12792739
TI  - Overexpression of the thrombospondin 2 (TSP2) gene modulated by the matrix
      metalloproteinase family expression and production in human colon carcinoma cell
      line.
AB  - Thrombospondin 2 (TSP2) is an extracellular matrix glycoprotein involved in tumor
      progression and angiogenesis. We evaluated whether overexpression of the TSP2
      gene show an alteration of various genes by cDNA arrays in the colon carcinoma
      cell line SW480. The transformants with the human TSP2 gene overexpression showed
      a down-regulation of matrix metalloproteinase 2 (MMP2) and MMP9 in comparison to
      those with vector-control. Protein production of MMP2 and MMP9 decreased in the
      transformants overexpressing the TSP2 gene. Conversely, the SW480 transformants
      showed up-regulation of MMP12 and MMP17. These results suggested that the TSP2
      gene is a multifunctional modulator of remodeling tissue in which matrix
      degradation is required.

PMID- 12792740
TI  - Phase II study of vinorelbine with low dose prednisone in the treatment of
      hormone-refractory metastatic prostate cancer.
AB  - A phase II trial of vinorelbine and low dose prednisone in hormone-refractory
      metastatic prostate cancer was conducted in order to investigate its safety,
      efficacy and impact on quality of life. Vinorelbine was administered at the dose
      of 25 mg/m(2) i.v. weekly for 12 weeks and then biweekly, along with 10 mg of
      daily oral prednisone until time of progression. Fourteen patients, median age of
      74 years, were treated. The treatment was generally well tolerated with
      leukopenia and anemia as the major side effects. One patient achieved partial
      remission and eleven remained with stable disease. One of the eleven patients
      with stable disease had a dramatic PSA response from 1000 to 236 ng/ml; seven of
      these progressed after week twelve when vinorelbine was given biweekly. PSA
      response occurred in 5 of 14 patients. The median time to progression was 28
      weeks and the median survival was 17 months. Nine out of the 14 accrued patients
      were evaluable for quality of life assessment. Five of them improved, three
      remained unchanged and two had a slight worsening. Four patients had improvement
      in pain control and fatigue. Our preliminary data suggest that the combination of
      vinorelbine/prednisone has modest activity in metastatic prostate cancer with a
      very favorable toxicity profile and is very well tolerated in this group of
      elderly patients.

PMID- 12792741
TI  - Recovery of stromal stem cells in bone sarcoma patients after chemotherapy:
      implication for cell-based therapy in bone defect reconstruction.
AB  - Bone sarcomas, such as osteosarcoma (OS) or Ewing sarcoma (ES), frequently arise
      in the intramedullary region of long bones. Patients affected by bone sarcomas
      are treated with preoperative aggressive chemotherapy immediately after
      diagnosis. After chemotherapy, patients undergo surgery that frequently entails
      the excision of wide bone segments. If a large segment of the bone is lost
      (defined as a critical defect) the patient undergoes bone reconstruction. Because
      bone marrow derived stromal stem cells (SSC) offer great promise for cell-based
      regenerative medicine in bone reconstruction, we investigated whether SSC could
      be isolated from chemotherapy-treated bone sarcoma patients. We also investigated
      whether chemotherapy modified SSC differentiation capability. We studied 9 SSC
      derived from OS and ES patients that had undergone chemotherapy and 5 SSC derived
      from bone sarcoma patients that had not undergone chemotherapy. SSC could be
      obtained from all the patients analyzed regardless of whether the patients
      received chemotherapy or not. Our results also showed that post-chemotherapy SSC
      can be cultured and expanded ex vivo, these cells retained the ability to
      differentiate toward the osteogenic lineage in vitro. In conclusion, our results
      support that SSC cells can be obtained from bone sarcoma patients that undergo
      chemotherapy and suggest that SSC can be used for cell-based bone reconstruction
      techniques in bone sarcoma patients treated with preoperative chemotherapy.

PMID- 12792742
TI  - Inactivation of the RASSF1A in osteosarcoma.
AB  - We investigated the expression and mutation of three isoforms of the Ras effector
      RASSF1 in 10 primary osteosarcomas and 6 osteosarcoma cell lines. RASSF1A was not
      expressed in 40% (4/10) of the primary osteosarcomas and 83.3% (5/6) of the
      osteosarcoma cell lines. RASSF1B and RASSF1C expression was absent in 30% (3/10)
      and 0% (0/10) of primary tumors, and 100% (6/6) and 0% (0/6) of osteosarcoma cell
      lines, respectively. Treatment of these cell lines with the DNA methylation
      inhibitor 5-aza-2'-deoxycytidine reactivated the transcription of RASSF1A, but
      not that of RASSF1B or RASSF1C. No somatic mutations were noted in RASSF1 in
      either the primary tumors or cell lines. Our data indicate that epigenetic
      inactivation of RASSF1A by hypermethylation of its promoter region is a frequent
      event, and may play an important role in the tumorigenesis of osteosarcomas.

PMID- 12792743
TI  - The site of injection of tumor cells in rats does not influence the subsequent
      distribution of metastases.
AB  - Our goal was to examine the influence of circulatory anatomy on the development
      of metastases. We compared the dissemination of tumor cells to different tissues
      at different stages in both an orthotopic and a heterotopic model of colon cancer
      in the rat. We used DHD/K12-PROb cells and two groups of BD-IX rats: group O
      (orthotopic), in which tumors were implanted by intramural injection of the
      cecum; and group H (heterotopic), in which cells were injected subcutaneously
      into the thoracic wall. Animals were assigned randomly to one of nine subgroups
      of each group in terms of the time between the injection of cells and euthanasia
      (from the third to the twelfth week). The presence of lung or liver
      macrometastases was recorded and tumor DNA was detected in lung and liver samples
      from all animals. We found that lung metastases developed in rats in groups O and
      H, but no metastases were found in liver parenchymas. The rates of detection of
      tumor DNA in lung and in liver samples were similar in the two groups. Our
      results suggest that the site of inoculation of DHD/K12-PROb cells did not
      influence the pattern of development of metastases. This does not support the
      proposed role of the circulatory anatomy in the distribution of metastases.

PMID- 12792744
TI  - Expression of the Mig (CXCL9) gene in murine lung carcinoma cells generated
      angiogenesis-independent antitumor effects.
AB  - We examined whether expression of monokine induced by IFN-gamma (Mig, CXCL9) in
      tumors could produce antitumor effects. Murine lung carcinoma cells (A11) were
      retrovirally transduced with the murine Mig gene (A11/Mig) and were inoculated
      into syngeneic mice. Although proliferation in vitro of A11/Mig cells was not
      different from that of parent cells, the growth in vivo of A11/Mig tumors was
      significantly retarded compared with that of parent tumors. The antitumor effect
      was dependent on the amount of Mig produced. We compared the expression level of
      marker genes of lymphocytes and endothelial cells between parent and A11/Mig
      tumor masses with reverse transcription-polymerase chain reaction. Expression of
      CD4, CD8alpha, CD40, CD86, CD28, CD31 and vascular endothelial growth factor was
      not different between the two tumor groups but expression of CD40 ligand, CD80,
      NK1.1 and CXCR3 was relatively lower in A11/Mig tumors. Although Mig is a
      chemotactic factor for activated T and NK cells and an inhibitor for
      angiogenesis, the present data suggested that production of Mig in tumors did not
      recruit activated T and NK cells efficiently or suppress angiogenesis. The
      antitumor effects by Mig could be independent of anti-angiogenesis and
      recruitment of T and NK cells.

PMID- 12792745
TI  - Phase I study of liposomal daunorubicin in relapsed and refractory acute myeloid
      leukemia.
AB  - Daunorubicin (DNR) is one of the most important cytotoxic agents in the treatment
      of acute myeloid leukemia (AML). Its use is usually limited by drug-induced
      cardiotoxicity depending on the cumulative dose administered. Liposomal
      encapsulation of DNR (DaunoXome, DNX) seems to reduce the risk of this severe
      side effect. To investigate the toxicity of DNX in heavily pretreated patients,
      we conducted a phase I trial, including patients (pts) older than 60 years with
      relapsed or refractory AML. DNX was used at doses of 40, 60, 75 and 90 mg/m(2),
      biweekly. Fourteen patients with a median age of 69 years (range, 63-77) were
      enrolled. A total of 49 courses of DNX were administered [3 pts at 40 mg/m(2)
      (for a total of 13 courses), 5 at 60 mg/m(2) (20 courses), 4 at 75 mg/m(2) (12
      courses), and 2 at 90 mg/m(2) (4 courses)]. The mean cumulative dose of DNX
      administered was 340 mg (range, 120-1200). A 20% decline in the left ventricular
      ejection fraction (LVEF) without clinical signs and symptoms of heart failure was
      noted in 2 patients after a cumulative DNX dose of 480 mg, both with pre-existing
      heart disease. Even at the highest cumulative doses of DNX, no further decline in
      LVEF was noted. Nausea, vomiting, alopecia and mucositis were absent. All
      patients had significant myelosuppression requiring transfusion support. During
      treatment, 3 patients showed a 25% reduction of leukemic blasts in the bone
      marrow, 3 patients had to be excluded due to AML progression after the 2nd DNX
      course, and 7 patients died during the first 6 weeks of treatment. We conclude
      from these data that DNX offers a less toxic alternative to DNR and other
      anthracyclines. Using DNX dosages of 40 to 90 mg/m(2) biweekly seems to have
      little anti-leukemic activity in a patient population heavily pretreated with
      anthracyclines.

PMID- 12792746
TI  - Endobronchial brachytherapy in combination with external beam irradiation in
      obstructing malignant bronchial tumors.
AB  - Endobronchial brachytherapy is commonly used in the palliative management of
      malignant airway obstructions. In the present study, we describe the results of
      brachytherapy (mean dose of 18 Gy), used in combination with external beam
      irradiation (mean dose of 50 Gy) in 30 patients who had primary bronchogenic
      carcinoma of the lung. The extent of airway obstruction was determined according
      to symptoms and by bronchoscopy. We found symptoms improved in nearly 37% of
      patients and 21 of 30 patients (70%), evaluated with bronchoscopy, showed a
      response when evaluated 3 to 6 months after brachytherapy. This endobronchial
      technique appeared to be a well-tolerated procedure with a low rate of acute
      toxicity. The immediate complication rate was 13%, during the follow-up 3 deaths
      were related to treatment, of which 2 were fatal haemoptysis (12 and 18 months
      after irradiation). We conclude that the combination of endobronchial
      brachytherapy with external beam irradiation may be useful and needs further
      comparisons with other irradiation procedures.

PMID- 12792747
TI  - Improvement of 10-year survival by Japanese radical lymph node dissection in
      patients with Dukes' B and C colorectal cancer: a 17-year retrospective study.
AB  - This study investigated whether the Japanese radical lymph node dissection (J
      LND) method was useful for improving the survival and outcome in patients
      undergoing surgical resection of primary colorectal cancer. The subjects were 434
      patients with primary colorectal cancer treated over 17 years. The 10-year
      survival (10-YS), the number of retrieved and metastatic lymph nodes (LN), the
      extent of lymph node dissection (D0-D3), and the extent of lymph node metastasis
      (n0-n4) were compared with Dukes' classification by the Kaplan-Meier curves, log
      rank test and multivariate analysis. Patients with a D number larger than their n
      number (D>n group) were defined as being treated according to J-LND principles,
      while those with a D number equal to their n number were used as controls (D=n
      group). Among Dukes' B patients, there was a significant difference of 10-YS
      between those with retrieval of > or =17 LN or < or =16 LN (p=0.0106). Among
      Dukes' C patients, a significant difference of 10-YS was observed between those
      with 1 metastatic node or > or =3 metastatic LN (p=0.0401). A significant
      difference of 10-YS was also noted between Dukes' C patients with D>n or D=n
      (p=0.0282). Multivariate analysis showed that retrieval of < or =16 LN (HR=9.051)
      and intramural invasion (se,si/a2,ai; HR=6.313) were independent determinants of
      10-YS in Dukes' B patients, while D=n (HR=2.354) and > or =3 metastatic LN
      (HR=2.210) were independent determinants in Dukes' C patients. These results
      suggest that the J-LND method should be performed to retrieve at least 17 nodes
      when serosal dimpling of the primary tumor is observed during surgery. Effective
      post-operative adjuvant therapy, such as combination chemotherapy and/or
      radiotherapy, should be provided for Dukes' C patients with D=n and/or > or =3
      metastatic nodes on histopathological examination.

PMID- 12792748
TI  - Hypermethylation of the CDKN2A gene in colorectal cancer is associated with
      shorter survival.
AB  - Promoter hypermethylation of the CDKN2A gene has been suspected to be involved in
      the carcinogenesis of colorectal cancers. However, the relations between CDKN2A
      hypermethylation and clinicopathological findings, and patient prognosis, remain
      inconclusive. We analyzed the CDKN2A methylation status in primary colorectal
      cancers using real-time methylation specific PCR (MethyLight) which enables
      quantitative measuring of the methylation level. CDKN2A promoter methylation was
      detectable in 55 (61.1%) of 90 tumor samples and the median level of the
      methylation was 0.187 (range 0.00-197.9). The methylation value of CDKN2A was
      correlated with certain clinicopathological findings, including tumor
      differentiation (p=0.018), and Dukes stage (p=0.016). In survival analysis, the
      CDKN2A methylation level was correlated with a poor prognosis of the patient with
      colorectal cancer for either all cases (p=0.014) or Dukes C (p=0.004) cases that
      were analyzed. These results suggest that CDKN2A methylation status is a
      prognostic factor in colorectal cancer and may be of use for the patient specific
      design of therapy.

PMID- 12792749
TI  - Lymphagenesis correlates with expression of vascular endothelial growth factor-C
      in colorectal cancer.
AB  - Lymphagenesis in gastrointestinal tumors is not well described. To clarify its
      presence and regulation, we assessed the microlymphatic count (MLC) in colorectal
      cancer patients. Lymphatic vessels were evaluated by enzyme-histochemistry for 5'
      nucleotidase (5'-NA). Since vascular endothelial growth factor (VEGF)-C is
      reportedly associated with lymphagenesis, the expression of VEGF-C protein was
      immunohistochemically assessed by the catalyzed signal amplification (CSA)
      method. MLC of peritumoral lesions was significantly higher than that of non
      cancer and intratumoral lesions (p<0.01); it increased where VEGF-C was highly
      expressed (p<0.01) and increased with the depth of invasion in peritumoral
      lesions. These results indicate significant findings at peritumoral lesion: that
      lymphagenesis may be elicited by tumor spread; that VEGF-C expression is
      associated with lymphagenesis and is a potent factor stimulating lymphagenesis.

PMID- 12792750
TI  - Differentiation of benign and malignant breast tumors using Doppler spectral
      parameters including acceleration time index.
AB  - Differentiation of breast cancer has been receiving increasing attention in
      attempts to minimize the numbers of excisional biopsies for benign tumors.
      Doppler spectral parameters, such as peak systolic velocity (PSV) and pulsatility
      index (PI), have been used but these are unable to differentiate breast cancers
      and benign tumors with adequate levels of specificity and sensitivity. The aim of
      this study was to determine whether the acceleration time index (ATI) could
      reliably differentiate breast tumors. In 102 breast masses, Doppler
      ultrasonography (US) was performed with a LOGIQ700MR. PSV, PI and ATI were
      calculated from intratumoral flow. Forty-eight malignant tumors were identified
      by histologic evaluation, 13 benign tumors were diagnosed by fine needle
      aspiration biopsy (FNAB) and 41 benign masses were diagnosed by characteristic
      gray-scale findings and long-term (>18 months) follow-up examinations. Doppler
      signals were detected in 35 of 54 (64.8%) benign lesions and in 46 of 48 (95.8%)
      breast cancers. PSV and PI value showed no statistical significance between
      malignant and benign lesions (PSV; p=0.1147, PI; 0.1506). ATI values were lower
      in benign lesions (p<0.0001). An ATI value of 0.14 seems to be the optimum
      threshold for the differentiation of benign and malignant lesions (79.4%
      sensitivity, 87.2% specificity). No malignant lesions were seen when the ATI
      value was <0.14 and the PI value was <1.1. ATI was found to be the most useful
      parameter for differentiating benign breast tumors from malignant ones.

PMID- 12792751
TI  - A feasibility study of paclitaxel and carboplatin therapy in Japanese patients
      with epithelial ovarian cancer.
AB  - The aim of this study was clarification of the feasibility, effects, and adverse
      events of combination chemotherapy with paclitaxel and carboplatin in Japanese
      women with epithelial ovarian cancer. In patients with stage Ic to IV epithelial
      ovarian cancer, primary cytoreductive surgery was performed. Paclitaxel (175
      mg/m(2)) was intravenously infused for 3 h. Subsequently, carboplatin was
      infused, with an area under the plasma concentration-time curve of 5. Ninety-one
      patients were enrolled in this study. The mean dose of paclitaxel at the sixth
      course was 161 mg/m(2). Of 51 patients, a complete response was observed in 19
      patients (37%), and a partial response in 23 patients (45%). The response rate
      for clear cell adenocarcinoma was 25%. With regard to adverse events, grade 4
      granulopenia was observed in 80% of patients, suggesting dose-limiting toxicity.
      However, none of the patients developed serious infection. With regard to non
      hematological toxicity, grade 2 or 3 alopecia, arythralgia/myalgia, and
      peripheral neurotoxicity were noted in 97, 29, and 20% of the patients,
      respectively. Although hematological toxicity was relatively marked, this regimen
      can be applied in Japanese women.

PMID- 12792752
TI  - Extracellular matrix remodeling may predominate over hepatocyte injury in
      hepatocellular carcinoma development.
AB  - It has been suggested that both extracellular matrix (ECM) remodeling and
      persistent hepatocyte injury play important roles in liver carcinogenesis
      process. It is, however, still controversial which factor plays a predominant
      role. The aim of the present study was to examine the role of each factor in the
      liver enzyme-altered preneoplastic lesions, focusing on the relationship between
      the hepatocyte injury and fibrosis extension. The effects of two similar herbal
      medicines (Sho-saiko-to and Saiko-keishi-to: TJ-9 and TJ-10, respectively) were
      elucidated on the hepatocyte injury, fibrosis and preneoplastic lesions
      development using a choline-deficient-L-amino acid-defined (CDAA) diet rat liver
      carcinogenesis model. TJ-9 prevented fibrosis and glutathione S-transferase
      placental form (GST-P)-positive preneoplastic lesion development without reducing
      the hepatocyte injury as indicated by the serum markers. TJ-10 significantly
      protected against the hepatocyte injury. However, it did not exert any inhibitory
      effect on fibrosis and the development of preneoplastic lesions. Our in vitro
      study revealed that TJ-9 markedly suppressed the hepatic stellate cell activation
      whereas TJ-10 did not. These results suggested that the ECM remodeling plays a
      more important role than the persistent hepatocyte injury in the liver enzyme
      altered preneoplastic lesion development in the rat.

PMID- 12792753
TI  - Genetic detection for hematogenous micrometastasis in patients with various types
      of malignant tumors using Uroplakin II derived primers in polymerase chain
      reaction.
AB  - The presence of circulatory metastasis is one of the most significant factors for
      poor-prognosis in patients with several types of cancer. To establish a sensitive
      reverse transcription PCR assay to detect micrometastasis in blood containing
      several cancer types, we first investigated Uroplakin II (UP II), a novel
      molecular marker for human transitional cell carcinoma of the bladder, in 25
      types of normal organs. In our study, UP II mRNA was detected in 10 types of
      organs, including bladder, kidney, lung and pancreas, but was not detected in
      normal lymph nodes or leukocytes. The data indicated evidence of UP II expression
      in various types of normal tissues by RT-nested PCR analysis. UP II mRNA was
      detected in 2 of 11 (18.2%) peripheral blood samples from lung cancer patients
      with no metastasis, and in 5 of 12 (41.7%) peripheral blood samples of lung
      cancer patients with metastasis. UP II was also detected in 6 of 16 (37.5%)
      peripheral blood samples of patients with pancreatic cancer. The data are
      particularly important in that the molecular detection of micrometastasis in the
      blood by means of UP II mRNA identification is feasible for UP II-positive
      neoplasms, including lung and pancreatic cancers.

PMID- 12792754
TI  - Influence of platelet-derived endothelial cell growth factor/thymidine
      phosphorylase on the cell cycle in head and neck squamous cell carcinoma in
      vitro.
AB  - Platelet-derived endothelial cell growth factor (PD-ECGF) was isolated as an
      endothelial mitogen from platelets and demonstrated to have angiogenic activity
      and thymidine phosphorylase (TP) activity. It was reported that the
      overexpression of PD-ECGF occurred with the rapid tumor growth in vivo. In this
      study, we transfected PD-ECGF into the head and neck squamous cell carcinoma cell
      line IMC-3 and investigated the property of transfectants in vitro. Highly
      overexpressed PD-ECGF transfectants rapidly grew compared with parental cells and
      control vector (CV) transfectants (p<0.05). The expression of cyclin D1 and
      cyclin E were more enhanced in PD-ECGF transfectants than parental cells and CV
      transfectants, while the p27kip1 was inhibited in PD-ECGF transfectants. In PD
      ECGF transfectants, S and G2/M-phase cells rapidly increased compared with
      parental cells and CV transfectants. These results showed that the cancer cell
      line with high expression of PD-ECGF had a rapid cell cycle and consequently
      facilitated rapid cell growth not only in vivo but also in vitro. Furthermore,
      the inhibitor of thymidine phosphorylase (TPI) suppressed the cell cycle and
      rapid cell growth that were acquired by PD-ECGF transfection. Since PD-ECGF was
      reported to be an independent, poor prognosis factor for head and neck cancer,
      TPI might be useful for the inhibition of cancer cell growth.

PMID- 12792755
TI  - Induction of apoptosis by fenretinide in tumor cell lines correlates with DLX2,
      DLX3 and DLX4 gene expression.
AB  - We investigated a possible relationship between apoptosis induction by
      fenretinide (4HPR) and the expression of a group of genes thought to be essential
      in morphogenesis and development, the DLX genes. We analyzed their expression
      under normal conditions or upon 4HPR stimulation in several tumor cell lines. We
      show that DLX2, DLX3 and DLX4 were expressed at higher levels in cell lines which
      where more sensitive to apoptotic induction, whereas DLX 5 and 6 appeared to
      segregate in a distinct functional compartment. Our data support the notion that
      DLX2, 3, 4 genes could participate in the control of 4HPR-mediated apoptosis,
      making them important molecules for the monitoring of therapy efficacy in cancer
      patients.

PMID- 12792756
TI  - Down-regulation of nitric oxide production by droloxifene and toremifene in human
      breast cancer cells.
AB  - We investigated the effect of tamoxifen, 4-OH tamoxifen, toremifene droloxifene,
      interferon-alpha2a, interferon-alpha2b and interferon-alpha2c, singly and in
      combination, for their effect on nitric oxide production by MCF-7 and ZR-75-1
      human breast cancer cells. Tamoxifen and 4-OH tamoxifen singly had no effect on
      nitric oxide production by either cell line. However, treatment with droloxifene
      or toremifene significantly reduced nitric oxide production by both MCF-7 and ZR
      75-1 human breast cancer cell lines. Combination treatment with anti-estrogens
      and interferon-alpha2a interferon-alpha2b or interferon-alpha2c had no
      synergistic or additive effect compared to each drug singly.

PMID- 12792757
TI  - Thin-section CT evaluation and pathologic correlation of therapeutic effect of
      neoadjuvant chemotherapy for axillary lymph nodes of clinically node-positive
      breast cancer patients.
AB  - In breast cancer patients, the number of surgically resected metastatic axillary
      lymph nodes has been considered to correlate closely with patient prognosis.
      Therefore, if metastatic lymph nodes could be controlled by neoadjuvant
      chemotherapy pre-operatively, we would be able to select a more appropriate
      regimen of post-operative chemotherapy for the individual patient and expect
      prognostic advantages of each patient with node-positive breast cancer. In this
      study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy
      for metastatic lymph nodes of node-positive breast cancer patients, using thin
      section (5 mm) helical CT (prone-position) with bolus injection of contrast
      agent. Between April 1994 and March 2002, 49 patients with node-positive breast
      cancer who had undergone thin-section CT study both before and following
      neoadjuvant chemotherapy enrolled in the study. The mean age of the patients was
      48.9 years and all were female. Concerning metastatic lymph nodes status, 45
      patients were classified as N1, 2 patients as N2, and another 2 as N3. In the
      evaluation, if at least one lymph node of >5 mm in the short diameter was
      detected on the CT study, the case was classified as node-positive. For lymph
      nodes of >1 cm in short diameter, fine-needle aspiration biopsy guided by
      ultrasonography was performed in order to obtain pathological confirmation of the
      existence of cancer metastasis. The diagnostic results of the CT study were
      compared with the pathologic findings of the resected specimen operatively. The
      neoadjuvant chemotherapy consisted of 3 to 4 times of CAF chemotherapy and an
      anti-estrogen agent, and intra-arterial infusion chemotherapy was also performed
      in patients with lymph node status of N2 or N3. The axillary status of 15 (30.6%)
      out of the 49 patients was evaluated as N0 after neoadjuvant chemotherapy, and 14
      out of the 15 patients were confirmed as node-negative based on the pathological
      results. Therefore, the diagnostic accuracy of the second CT study performed
      following the neoadjuvant chemotherapy was 85.7%, with a sensitivity of 96.6%, a
      specificity of 70.0%, a positive predictive value of 82.4%, and a negative
      predictive value of 93.3%. The results described above demonstrate that such a
      sophisticated and precise CT study performed following neoadjuvant chemotherapy
      and evaluating the therapeutic effect on metastatic lymph nodes following the
      neoadjuvant chemotherapy can help to determine an appropriate regimen of post
      operative chemotherapy and be of prognostic advantage in patients with node
      positive breast cancer.

PMID- 12792758
TI  - High serum soluble E-selectin levels are associated with postoperative
      haematogenic recurrence in esophageal squamous cell carcinoma patients.
AB  - E-selectin has been reported to be associated with haematogenic metastasis in
      various cancer patients. In order to evaluate the risk of postoperative
      haematogenic recurrence of esophageal squamous cell carcinoma (SCC) patients, we
      examined the preoperative serum levels of soluble E-selectin and
      clinicopathological data of the patients. Preoperative serum was obtained from
      135 esophageal SCC patients who received esophagectomies from 1990 to 1998. Serum
      soluble E-selectin levels were measured by means of enzyme linked immunoreactive
      synthesis assay (ELISA). The expression of sialyl Lewis A and X antigens were
      evaluated in 58 out of 135 patients. Thirty-five patients (25.9%) had
      haematogenic recurrence in their postoperative course. Serum soluble E-selectin
      levels of the haematogenic recurrence group (mean 55.6 ng/ml) were significantly
      higher than those of the non-haematogenic recurrence group (mean 41.1 ng/ml).
      When the cut-off level of soluble E-selectin was 56 ng/ml, the logistic
      regression analysis showed that high serum soluble E-selectin levels, lymph node
      metastasis and intraepithelial spread were associated with postoperative
      haematogenic recurrence of the esophageal SCC patients (OR 2.99, p=0.047, OR
      4.94, p=0.009 and OR 5.0, p=0.019. respectively). Univariate analysis revealed
      that the patients with a high serum soluble E-selectin level tended to have poor
      survival (p=0.078) and Cox multivariate analysis revealed that a high serum
      soluble E-selectin level was a prognostic factor in esophageal SCC patients (RR
      1.84, p=0.065). The patients with a high serum soluble E-selectin concomitant
      with expression of sialyl Lewis antigens had a significant risk of postoperative
      haematogenic recurrence (p=0.005). These results indicated that preoperative high
      serum soluble E-selectin was a risk factor in the development of postoperative
      haematogenic recurrence and was a prognostic factor in esophageal SCC patients.

PMID- 12792759
TI  - Negative hMSH2 protein expression in pancreatic carcinoma may predict a better
      prognosis of patients.
AB  - The prognostic values of immunohistochemical staining for hMSH2 and hMLH1 in
      patients with pancreatic carcinomas were investigated. Fifty-five patients with
      histologically proven pancreatic carcinomas were studied. Immunohistochemical
      staining for hMSH2 and hMLH1 was performed by avidin-biotin-peroxidase complex
      method with a catalyzed signal amplification system. Tumor cells that exhibited
      an absence of nuclear staining in the presence of non-neoplastic cells with
      nuclear staining were considered to have an abnormal pattern. Four tumors (7.3%)
      demonstrated abnormal hMS2-negative staining. One tumor (1.8%) had abnormal hMLH1
      negative staining and this tumor showed negative hMSH2 staining. No particular
      clinicopathologic factor such as tumor location, histology, T-factor, N-factor
      and TNM-stage were observed in patients with negative hMSH2 staining tumors.
      Median survival time (MST) of patients with hMSH2-negative tumors was
      comparatively longer than that of patients with hMSH2-positive tumors, however,
      there was no significant difference between MSTs of the two groups (56 months vs.
      14 months; p=0.16). We concluded that negative hMSH2 immunohistochemical staining
      in the pancreatic carcinomas may demonstrate certain patients, but not all, who
      had microsatellite instability-positive tumors. The patients with hMSH2-negative
      tumors may have better prognoses than those with hMSH2-positive tumors. To
      clarify these findings, further large number of pancreatic carcinomas must be
      investigated.

PMID- 12792760
TI  - Effect of hepatocyte growth factor on invasion of prostate cancer cell lines.
AB  - Hepatocyte growth factor (HGF) was suggested to play an important role in the
      regulation of mitogenesis, motogenesis, angiogenesis, migration and invasion for
      various types of cells, and acts through a specific membrane receptor encoded by
      c-met proto-oncogene. However, the mechanism of the effect of HGF on tumor
      invasion of prostate cancer cells remains unclear. We investigated the effect of
      HGF on the invasion of PC-3 and DU-145 prostate cancer cells through a
      reconstituted basement membrane (Matrigel), the haptotactic migration to
      fibronectin substrate, the expression of protein and mRNA for matrix
      metalloproteinases (MMP)-1 and -9, membrane-type 1-MMP (MT1-MMP), urokinase-type
      plasminogen activator (u-PA) and its receptor (uPAR). HGF increased both Matrigel
      invasion and haptotactic migration of prostate cancer cells. Furthermore, HGF
      also increased the production of MMP-1 and -9, MT1-MMP, u-PA and uPAR of these
      cells. These results suggested that HGF increased the invasive potential of
      prostate cancer cells probably through enhancement of cell motility and the
      production of MMPs and u-PA.

PMID- 12792761
TI  - Membranous lipodystrophy (Nasu-Hakola disease) presenting an unusually benign
      clinical course.
AB  - Membranous lipodystrophy is known as Nasu-Hakola disease. The main symptoms of
      membranous lipodystrophy are those of a progressive presenile dementia due to
      sclerosing leukoencephalopathy with skeletal polycystic lesions. There is no
      report detailing long-term follow-up of patients with membranous lipodystrophy.
      We present a 56-year-old woman with this disease who has not manifested any
      typical neuropsychiatric symptoms during the 16-year follow-up, and thus has had
      an unusually benign clinical course. The patient underwent curettage and bone
      grafts. Periodic examinations have been continued for 16 years from discharge. No
      recurrence of lesions or occurrence of new cystic lesions has been noted.
      Computerized tomography and magnetic resonance imaging of the brain revealed none
      of the abnormal change which are reported in this disease. Our findings suggest
      that some patients with this disease may be fortunate enough to follow a
      relatively benign clinical course.

PMID- 12792762
TI  - In vitro demonstration of breast cancer tumor cell sub-populations based on
      interleukin-1/tumor necrosis factor induction of interleukin-8 expression.
AB  - Interleukin-8 (IL-8) has been identified as an angiogenesis factor (AF) as well
      as a tumor cell chemotactic factor and mitogen. Recent in vivo studies have
      demonstrated the expression of IL-8, IL-1 and TNF, as well their receptors, on
      various sub-populations of tumor cells in human breast cancer (HBC). Since pro
      inflammatory cytokines such as IL-1 and TNF are known inducers of IL-8 in non
      tumor cells, we hypothesize that IL-1/TNF may act as an IL-8 inducer in HBC, and
      thus enhance HBC tumor progression. To begin to test this hypothesis, we
      evaluated the ability of: a) human breast cancer cell lines (BCC) and normal
      human breast epithelial cell lines (BEC) to produce IL-8 in vitro; and b) IL-1
      and TNF to regulate the expression of IL-8. In general, basal IL-8 expression was
      low in all 8 cell lines examined. TNF-alpha and TNF-beta induced a 3- to 24-fold
      increase in IL-8 protein expression of BEC, and a 2- to 8-fold increased IL-8
      expression in estrogen-independent BCC cell lines and no significant IL-8
      expression in estrogen-dependent cell lines. Conversely, IL-1alpha and IL-1beta,
      induced a 5- to 104-fold stimulation of BEC and a 330 to 1,138-fold increase in
      IL-8 expression in estrogen independent BCC. These observations demonstrate the
      ability of HBC cells to produce IL-8 in vitro and further indicate that IL-1 is a
      potent inducer of IL-8 expression by BEC and BCC. Furthermore, this in vitro data
      support the hypothesis, that within the HBC tumor microenvironment, tumor cells
      exist that respond to pro-inflammatory cytokine (IL-1) stimulation (i.e. MDA-MB
      231) and those that do not (i.e. MCF-7). Additionally, HBC tumor cell lines that
      can be induced to express high levels of IL-8 tend to be associated with a more
      aggressive phenotype.

PMID- 12792763
TI  - Human mast cells induce caspase-independent DNA fragmentation in leukemic T
      cells.
AB  - Mast cells are known to play an important role in inflammation and host defense.
      Recent evidence suggests that mast cells may also participate in immune
      surveillance against cancer cells. In this study, we demonstrate that human mast
      cells are able to trigger apoptosis in Jurkat T leukemia cells. Fragmentation of
      Jurkat cell DNA was detectable by JAM assay within 4 h of exposure to HMC-1 mast
      cells or cultured human cord blood-derived mast cells. HMC-1 mast cells that were
      fixed with paraformaldehyde retained the ability to induce apoptosis in Jurkat
      cells while cell-free conditioned supernatants from HMC-1 cell cultures failed to
      elicit DNA fragmentation, suggesting that mast cells mediate anti-tumor activity
      via a cell-surface molecule. Surprisingly, the apoptosis-inducing activity of HMC
      1 mast cells was not mediated by known tumor necrosis factor (TNF) superfamily
      members (TNF-alpha, Fas ligand, TRAIL, TWEAK), nor did the fragmentation of
      Jurkat cell DNA by mast cells require the activity of caspase-3, -8, or -9.
      Collectively, these data indicate that mast cells trigger caspase-independent
      apoptosis in leukemic cells via a novel cell-surface molecule, and are consistent
      with a role for mast cells as anti-tumor effector cells.

PMID- 12792764
TI  - The mouse mammary tumor virus-like env gene sequence is not detectable in breast
      cancer tissue of Austrian patients.
AB  - The mammary mouse tumor virus (MMTV) has been related to human breast cancer in
      previous studies, but these have yielded contradictory results. An MMTV env gene
      like sequence was detectable in a relatively high proportion (38%) of human
      breast cancer tissues. The aim of this study was to determine the proportion of
      this 660 bp MMTV env gene-like sequence in a population of Austrian breast cancer
      patients. We performed PCR, repeat PCR, and nested PCR. We did not find any
      exogenous MMTV env gene sequences in the 50 DNA samples of human breast cancer
      tissue nor in 22 breast cancer cell lines including MCF-7, which has previously
      been described as a positive control.

PMID- 12792766
TI  - Genetic characterization of lung metastases in renal cell carcinoma.
AB  - Prognosis of patients with renal cell carcinoma (RCC) is mainly determined by
      metastases. The understanding of the metastatic process will give the basis for a
      differential diagnosis leading to an individual prognosis and to new
      therapeutical strategies. In order to define specific genetic alterations which
      are common in renal cancer metastases of the lung, we performed comparative
      genomic hybridization (CGH) on metastases and in some cases on their related
      primary renal tumors. For CGH, DNA was isolated from 2 or 5 paraffin sections (5
      micro m). Tumor and normal (control) DNAs were amplified by DOP-PCR and labeled
      with biotin-dUTP and digoxigenin-dUTP, respectively. Hybridization and detection
      were carried out according to standard protocols. In 33 out of 40 metastases,
      genetic alterations were detected, most frequently these were losses of
      chromosomes 3p (74%), 8p (31%), 9 or 9q (34%), 14 [26%, 18q (40%) and gains of
      chromosome 5/5q 34%], 7 (31%) and 12 (26%). Combination of loss of 8p and gain of
      8q occurred frequently. The mean number of aberrations per tumor was 8.1 (1-11).
      The comparison of alterations in related primary and metastatic tumors showed
      identical alterations in 5 out of 8 cases. This study demonstrates, that lung
      metastases from renal cell carcinoma are characterized by an accumulation of
      specific genetic alterations which show a clonal relationship to the related
      primary tumors.

PMID- 12792765
TI  - Frequent death-associated protein-kinase promoter hypermethylation in brain
      metastases of solid tumors.
AB  - Death-associated protein (DAP) kinase is a gene that participates in apoptosis
      induced by interferon gamma. It appears to play a role in lung cancer metastasis
      in animal models, suggesting that DAP-kinase may function as a metastasis
      suppressor by inducing apoptosis. Expression silencing through CpG island
      methylation of DAP-kinase has been frequently found in connection with adverse
      survival, as cells lacking DAP-kinase appear to be more invasive and more
      metastatic in lung cancer. The purpose of this study was to analyze the promoter
      methylation status of DAP-kinase gene in brain metastases of solid tumors.
      Methylation-specific PCR was performed on ten brain metastasis samples derived
      from malignant melanoma (three cases), lung cancer (two), breast carcinoma (two),
      ovarian carcinoma (two) and colon carcinoma (one case), and in corresponding
      peripheral blood DNA samples. Two normal brain tissue samples were also analyzed,
      no promoter hypermethylation was observed in either case. DAP-kinase
      hypermethylated alleles were identified in nine metastases (90%), and in
      peripheral blood lymphocytes DNA from four cases. Our data suggest that silencing
      of DAP-kinase through promoter hypermethylation is a common event in the
      multistep process of tumor metastasis, including brain involvement.

PMID- 12792767
TI  - BAT-26 microsatellite instability does not correlate with the loss of hMLH1 and
      hMSH2 protein expression in sporadic endometrial cancers.
AB  - Microsatellite instability (MSI) is detected in about 20-25% of endometrial
      cancers (ECs). Incidence of this alteration correlates with lack of expression of
      certain mismatch repair genes such as hMLH1 and hMSH2. Although assessment of
      several markers has been proposed for identification of microsatellite unstable
      tumours, BAT-26, a mononucleotide microsatellite repeat, has been shown to be
      highly efficient when used as a single marker. The aim of the study was to
      evaluate instability within BAT-26 and expression of hMLH1 and hMSH2 proteins in
      sporadic endometrial cancer as well as to correlate these findings with
      histopathologic and clinical characteristics of tumours. Samples of 88 (74
      endometrioid and 14 non-endometrioid) ECs were investigated for instability
      within BAT-26 by means of PCR and expression of hMLH1 and hMSH2 proteins using
      immunohistochemistry. BAT-26 MIS was discovered in 23.9% of endometrial cancers.
      Incidence of MSI did not correlated with grade, stage or depth of invasion. BAT
      26 MSI was more frequent in non-endometrioid compared to endometrioid tumours
      (35.7% vs. 21.6%, respectively), but the difference was not statistically
      significant. Lack of hMLH1 and hMSH2 protein expression was detected in 21.6 and
      15.9% of ECs, respectively, and did not correlate with clinicopathologic features
      of tumours. Loss of both hMLH1 and hMSH2 protein expression was similar in BAT-26
      stable and unstable cancers. All cases of non-endometrioid tumours with BAT-26
      MSI were positive for hMLH1. We can conclude that BAT-26 used alone may not be a
      reliable marker for identification of sporadic ECs with microsatellite
      instability induced by deficient expression of hMLH1 and hMSH2.

PMID- 12792768
TI  - Expression status of Pin1 and cyclins in oral squamous cell carcinoma: Pin1
      correlates with Cyclin D1 mRNA expression and clinical significance of cyclins.
AB  - Phosphorylation on serine or threonine residue preceding proline (Ser/Thr-Pro) is
      a key regulatory mechanism. The conformation of certain phosphorylated Ser/Thr
      Pro bonds is regulated specifically by the prolyl isomerase Pin1. It has been
      reported that Pin1 is strikingly overexpressed in a subset of human tumors. A
      differential-display screen reveals that Pin1 increases the transcription of
      several beta-catenin target genes, including those encoding cyclin D1 and c-Myc.
      Pin1 cooperates with Ras signaling in increasing the transcriptional activity of
      c-Jun towards cyclin D1. We have previously reported that Pin1 is overexpressed
      in oral squamous cell carcinoma (OSCC) and its level correlates with Cyclin D1
      expression. However, the analysis of the relationship between Pin1 and other
      cyclin genes has not been demonstrated in human OSCC. We examined Pin1 mRNA and
      protein expressions in OSCC cell lines, and analyzed Pin1/cyclins expression by
      RT-PCR. We report that Pin1 mRNA correlates with Cyclin D1 mRNA expression and
      the expression of many cyclin genes is associated with lymph node metastasis in
      OSCC. These results indicate that Pin1 is a regulator of Cyclin D1 expression in
      OSCC and might have a role in oncogenesis; and the expression of many cyclin
      genes will be an indicator of lymph node metastasis in OSCC.

PMID- 12792769
TI  - Specific cytoskeleton changes during apoptosis accompanying induced
      differentiation of HL-60 myeloid leukemia cells.
AB  - Changes in actin filaments and microtubules were studied in the human myeloid
      leukemia HL-60 cell line during the process of apoptotic cell death accompanying
      induced differentiation. These cytoskeleton changes were assessed during a 6-day
      cultivation in the presence of 10(-6) M all-trans retinoic acid (ATRA), a
      specific inductor of both differentiation into granulocytes and apoptosis, or
      during a 18-day cultivation in the presence of 1.6 nM phorbol myristylacetate
      (PMA), which induces differentiation into macrophages. The processes were studied
      at the morphological level by fluorescence microscopy and, quantitatively, by
      flow cytometry. The results showed that the actin cytoskeleton underwent specific
      structural changes during the apoptotic process, but microtubules were not
      actively involved. In the initial stages of apoptosis, a fine meshwork of actin
      filaments turned into actin granules that, in the final stages, were transformed
      into a network of long actin fibres distributed throughout the cytoplasm. These
      actin structures were considered to play an active role in two main morphological
      events of apoptosis - formation of blebs and final cell disintegration into
      apoptotic bodies. In addition, high proportion of cells with apoptotic nuclei and
      completely destroyed actin structures were found in the differentiating ATRA
      treated cell population. Flow cytometric measurement of cytoskeletal proteins
      content confirmed all these observed changes. Alterations and rearrangements of
      both cytoskeletal structures are common for the apoptotic cell death of HL-60
      cells and they are independent on the course of differentiation.

PMID- 12792770
TI  - Epstein-Barr virus-associated gastric carcinoma in Cali, Colombia.
AB  - To estimate the incidence of Epstein-Barr virus-associated gastric carcinoma (EBV
      GC) in Colombia and to clarify its clinicopathological features, we examined 178
      consecutive gastric carcinoma cases, diagnosed during the period from 1996 to
      1998, at Hospital Universitario del Valle in Cali, Colombia. The mean age of the
      cases was 60 years in males and 58 years in females. Using in situ hybridization
      assay of EBV-encoded small RNA-1 in paraffin-embedded tissue samples, we
      identified 23 cases of EBV-GC (13%). After excluding remnant carcinoma, which was
      found to be EBV-negative in this series, there were 19 (18%) male and 4 (6%)
      female EBV-GC cases, and the male predominance was statistically significant
      (P=0.004). The proportion of EBV-GCs decreased with age (P for trend = 0.022).
      Using sex- and age-specific proportions of EBV-GCs estimated by logistic models
      and gastric cancer incidence in Cali, which was obtained from tumor registry
      during the period 1987-1991, we estimated sex- and age-specific incidence of EBV
      GCs. The incidence of EBV-GCs (per 100,000 person-years) was 4.1 and 1.4 among
      men and women, respectively, after age adjustment using the standard world
      population. Pathological features of EBV-GCs were also examined. EBV-GCs
      accounted for 33% (8/24) of carcinomas located in the stomach cardia, 14% (6/43)
      of carcinomas in the middle-part of the stomach, and 7% (6/81) of carcinomas in
      the antrum. The difference by tumor location was statistically significant
      (P=0.009). Histology-specific analysis using Lauren classification revealed that
      the proportion of EBV-GCs was not different in intestinal- and diffuse-type
      carcinomas (13% in both types). When the classification scheme of the Japanese
      Research Society for Gastric Cancer was used, EBV-GCs were identified more
      frequently in moderately differentiated tubular adenocarcinoma, and solid poorly
      differentiated adenocarcinoma when compared to other histological types. No
      lymphoepitelioma-like histology was found in the present series. The frequency of
      EBV-GC was slightly higher in advanced tumors, which involved serosa. Further
      analysis of clinico-pathological features of EBV-GC using a larger number of
      cases would give invaluable insights into its etiology.

PMID- 12792772
TI  - Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the
      underlying mechanisms (review).
AB  - Cancer, next only to heart diseases, is the second leading cause of deaths in the
      United States of America and many other nations in the world. The prognosis for a
      patient with metastatic carcinoma of the lung, colon, breast, or prostate (four
      of the most common and lethal forms of cancer, which together account for more
      than half of all deaths from cancer in the USA), remains dismal. Conventional
      therapeutic and surgical approaches have not been able to control the incidence
      of most of the cancer types. Therefore, there is an urgent need to develop
      mechanism-based approaches for the management of cancer. Chemoprevention via non
      toxic agents could be one such approach. Many naturally occurring agents have
      shown cancer chemopreventive potential in a variety of bioassay systems and
      animal models, having relevance to human disease. It is appreciated that an
      effective and acceptable chemopreventive agent should have certain properties:
      (a), little or no toxic effects in normal and healthy cells; (b), high efficacy
      against multiple sites; (c), capability of oral consumption; (d), known mechanism
      of action; (e), low cost; and (f), acceptance by human population. Resveratrol is
      one such agent. A naturally occurring polyphenolic antioxidant compound present
      in grapes, berries, peanuts and red wine. In some bioassay systems resveratrol
      has been shown to afford protection against several cancer types. The mechanisms
      of resveratrol's broad cancer chemopreventive effects are not completely
      understood. In this review, we present the cancer chemopreventive effects of
      resveratrol in an organ-specific manner. The mechanisms of the
      antiproliferative/cancer chemopreventive effects of resveratrol are also
      presented. We believe that continued efforts are needed, especially well-designed
      pre-clinical studies in the animal models that closely mimic/represent human
      disease, to establish the usefulness of resveratrol as cancer chemopreventive
      agent. This should be followed by human clinical trials in appropriate cancer
      types in suitable populations.

PMID- 12792771
TI  - Dendritic cell-based glioma immunotherapy (review).
AB  - Despite advances in radiation and chemotherapy along with surgical resectioning,
      the prognosis of patients with malignant glioma is poor. Among the new treatments
      currently being investigated for malignant glioma, immunotherapy is theoretically
      very attractive, since it offers the potential for high tumor-specific
      cytotoxicity. There are increasing reports demonstrating that systemic
      immunotherapy using dendritic cells is capable of inducing an antiglioma
      response. Therefore, dendritic cell-based immunotherapy could be a new treatment
      modality for patients with glioma. In this review, we will discuss the
      implications of these findings for glioma therapy. A literature review of
      dendritic cell-based glioma immunotherapy was used to overview the dendritic cell
      in immunobiology, in the central nervous system and in tumor immunology, glioma
      associated antigens, dendritic cell therapy in animal glioma model, dendritic
      cell therapy in clinical trials and future directions in dendritic cell therapy.
      Dendritic cell-based immunotherapy strategies appear promising as an approach to
      successfully induce an antitumor immune response and increase survival in
      patients with glioma. Dendritic cell therapy of glioma seems to be safe and
      without major side effects. Its efficacy should be further determined in
      randomized, controlled clinical trials. The development of methods for
      manipulating dendritic cells for the purpose of vaccination will enhance the
      clinical usefulness of these cells for biotherapy for malignant glioma.

PMID- 12792774
TI  - Numerical aberrations of chromosome 17 and the 9p21 locus are independent
      predictors of tumor recurrence in non-invasive transitional cell carcinoma of the
      urinary bladder.
AB  - Since the majority of patients with non-invasive (stage pTa) bladder carcinoma
      experience tumor recurrence, the identification of prognostic markers for
      assessing the biologic behavior of tumors is of high clinical interest. In this
      retrospective study, we investigated the prognostic value of numerical
      aberrations of chromosomes 3, 7, 17 and of the 9p21 gene locus in 71 pTa bladder
      carcinomas using the UroVysion test. This recently developed multi-probe
      fluorescence in situ hybridization (FISH) test, which simultaneously stains the
      9p21 locus and the centromer regions of chromosomes 3, 7 and 17, was applied on
      paraffin sections from formalin-fixed tumor specimens. All tumors were evaluated
      for twelve different criteria, among which were: polysomy 3, 7 or 17 in > or =10%
      of tumor cells, pentasomy or higher polysomy 3, 7 or 17 in > or =1 tumor cell,
      and loss of both 9p21 alleles in > or =10% of tumor cells. The latter parameter
      was the most frequent chromosomal aberration (detected in 83% of the tumors),
      while polysomies 3, 7 and 17 were registered in 27, 13 and 12% of the cases,
      respectively. Most of the parameters were found at higher frequencies in G3
      tumors compared to G1 or G2 tumors. None of the parameters correlated with
      progression-free survival, but polysomy 3 (p=0.029), polysomy of at least one of
      the chromosomes 3, 7 or 17 (p=0.032), pentasomy/higher polysomy 17 (p=0.007), and
      loss of 9p21 (p=0.026), correlated significantly with recurrence-free survival.
      Of these, pentasomy/higher polysomy 17 (p=0.015) and loss of 9p21 (p=0.036) were
      identified as independent predictors of tumor recurrence in a multivariate Cox
      regression analysis that also included tumor grade. In conclusion, we suggest
      that evaluation of numerical aberrations of chromosome 17 and the 9p21 locus may
      represent a useful tool to assess tumor recurrence of pTa bladder carcinomas more
      accurately.

PMID- 12792773
TI  - Gene-expression profiles of human tumor xenografts in nude mice treated orally
      with the EGFR tyrosine kinase inhibitor ZD1839.
AB  - To date, no single or multiple molecular markers have been successful in
      predicting sensitivity of individual patients to anti-cancer drugs. As the nature
      of a specific cancer is considered to be defined by the proteins being expressed
      in the tumor cells, systematic analysis of gene-expression profiles may provide
      information reflecting sensitivity of a given tumor to certain drugs. Recent
      progress in genome technology has enabled us to examine expression profiles of
      thousands of genes in a single experiment. We used this approach to examine 13
      xenografts of human tumors implanted into nude mice for sensitivity to an orally
      active, selective epidermal growth factor receptor tyrosine kinase inhibitor
      (EGFR-TKI), ZD1839 (Iressa). To identify genes that might be associated with
      sensitivity to this drug we used a cDNA microarray representing 23,040 genes to
      analyze expression profiles of the 13 xenografts and identified 114 genes whose
      expression levels correlated significantly with sensitivity of the tumors to
      ZD1839. We then investigated alteration of expression profiles in response to the
      ZD1839 treatment in four non-small cell lung cancer (NSCLC) xenografts, of which
      two (LC6 and LC11) were sensitive and the other two (Lu116 and L27) were
      resistant to this EGFR-TKI. Systematic analysis of expression at various time
      points during oral treatment for 14 days, compared with corresponding untreated
      samples, identified a set of genes whose expression levels changed in the two
      sensitive tumors but not in the two resistant tumors. The data obtained here
      should provide useful information on the molecular mechanism underlying clinical
      responses to EGFR-TKIs, aid the development of novel therapies for lung cancer,
      and potentially identify predictive molecular markers for sensitivity to ZD1839.

PMID- 12792775
TI  - Differential gene expression profiles and identification of the genes relevant to
      clinicopathologic factors in colorectal cancer selected by cDNA array method in
      combination with principal component analysis.
AB  - The clinical outcome of patients with colorectal cancer frequently varies even if
      they are at the same clinicopathologic stage. Alternative superior tumor markers
      of colorectal cancer are needed for prediction of clinical outcome. To clarify
      the regulatory factors in colorectal cancers, we examined differential expression
      profiles using cDNA macroarray technique with surgically resected specimens
      obtained from the patients with colorectal cancer. The gene profiles by an
      average-linkage hierarchical clustering analysis were found to be almost
      separable into two groups: tumor group and normal mucosa group. The relationship
      between several clinicopathologic factors and cancer related genes were
      investigated by using statistical analyses including principal component analysis
      (PCA). c-myc-binding protein MM-1, and c-jun proto-oncogene were identified as
      possible markers of tumor histology and clinical prognosis and early growth
      response protein 1 (EGR1) was selected to play an important role in progression
      of clinical stage. We conclude that, with PCA method, we successfully selected
      the genes relevant to clinicopathologic factors using limited population of
      clinical samples.

PMID- 12792776
TI  - Protease-activated receptor-2 expression and the role of trypsin in cell
      proliferation in human pancreatic cancers.
AB  - Protease-activated receptor (PAR)-2 is a G protein-coupled receptor that is
      activated by trypsin. The purpose of this study was to examine PAR-2 expression
      and the role of trypsin in cell proliferation in human pancreatic cancer cells.
      All four pancreatic cancer cell lines studied, from well to undifferentiated
      types, AsPC-1, BxPC-3, Panc-1, and MIAPaCa-2, had significant levels of PAR-2
      mRNA detected by reverse transcription-polymerase chain reaction, and showed a
      band of about 55 kDa corresponding to the known molecular weight of PAR-2: AsPC
      1, BxPC-3 and Panc-1 showed a strong band, and MIAPaCa-2 showed a weak one.
      Immunocytochemically, AsPC-1, BxPC-3, and Panc-1 showed intense immunostaining
      for PAR-2, predominantly in the plasma membrane, while in MIAPaCa-2,
      immunostaining was weak. Proliferative activity of AsPC-1 cells was increased by
      concentrations of trypsin as low as 10 nM, and activity peaked at a concentration
      of 100 nM, representing almost 60% of that induced by 10% fetal bovine serum. In
      contrast, trypsin had no significant effect on proliferation of MIAPaCa-2 cells.
      These findings suggest that trypsin plays a role in the growth of PAR-2-positive
      pancreatic cancer cells and serves as a potent mitogen in vitro, functioning as a
      growth factor.

PMID- 12792777
TI  - Ring chromosomes and low-grade gene amplification in an atypical lipomatous tumor
      with minimal nuclear atypia.
AB  - Atypical lipomatous tumors (ALTs) are characterized by supernumerary ring
      chromosomes and/or giant marker chromosomes, which typically are composed of
      interspersed, amplified 12q-sequences, are C-band negative, lack alpha-satellite
      sequences, and display high copy numbers of several oncogenes, including HMGA2
      (a.k.a. HMGIC) and MDM2, from the 12q13-15 region. In the present study, we
      report the cytogenetic and molecular genetic findings in an ALT with minimal
      nuclear atypia from a 16-year-old boy. At G-banding analysis, 1-3 supernumerary
      ring chromosomes were detected. Combined binary ratio labeling fluorescence in
      situ hybridization (COBRA-FISH) showed that the rings were entirely composed of
      material from chromosome 12, and by further FISH analysis with locus-specific
      probes it was revealed that they consisted of two tandemly arranged copies of the
      segment 12p11.2-p13.2 to 12q21.2-q23.1. Within that segment of chromosome 12,
      there was a small deletion including the HMGA2 locus. There was no variation in
      ring size and no interphase bridges could be detected, indicating that the ring
      chromosomes were mitotically relatively stable. The present case thus adds
      support to the concept that there exists a subset of ALT with limited or minimal
      nuclear atypia and low-level amplification of 12q sequences, further suggesting
      the possibility of a molecular genetic continuum between lipoma and classical
      examples of ALT. Furthermore, the present data strongly imply that it is the
      composition of the rings rather than the ring chromosome formation as such that
      causes the genetic instability and nuclear atypia frequently seen in ALTs.

PMID- 12792778
TI  - Inhibition of metastatic brain tumor growth by intramuscular administration of
      the endostatin gene.
AB  - The cancer patients suffering from brain metastases are basically incurable. The
      conventional tumoricidal strategies frequently cause severe side effects instead
      of life prolongation of such patients. On the other hand, antiangiogenic therapy
      seems to be a promising strategy to avoid such unfavorable effects. In the
      present study, we experimentally investigated tumor dormancy effect of the
      excessively produced endostatin, a potent angiostatic factor, by intramuscular
      administration of the endostatin gene against primary cancer and metastatic brain
      tumor. For this purpose, we established a model system in which FM3A P-15 cells,
      a high metastatic mouse breast cancer cell line, were inoculated simultaneously
      into the brain as an artificially metastatic brain tumor (herein referred as
      "metastatic brain tumor") and the mammary pad as a primary cancer (referred as
      "primary breast cancer"), and utilized a non-viral system to deliver an
      expression plasmid encoding a secretable form of mouse endostatin into muscle
      tissues. The plasmid vector formulated with the synthetic polymer,
      polyvinylpyrrolidone, was administrated at 3 and 10 days after the inoculation of
      FM3A P-15 cells. A significant increase in the serum level of endostatin was
      achieved at 7 days after second administration of the plasmid vector (p=0.0066).
      Consequently, the growth of metastatic brain tumor was significantly retarded
      (p=0.0455), while no significant change in the weight of primary breast cancer
      was observed (p=0.1531). Intratumoral microvessel density in metastatic brain
      tumor but not in primary cancer as revealed by Factor VIII immunohistochemistry
      was significantly decreased in the endostatin gene-administrated group
      (p=0.0027). In conclusion, the present study demonstrates the potential efficacy
      of intramuscular delivery of antiangiogenic gene for treatment of metastatic
      brain tumor.

PMID- 12792779
TI  - Oncoprotein expression of E6 and E7 does not prevent 5-fluorouracil (5FU)
      mediated G1/S arrest and apoptosis in 5FU resistant carcinoma cell lines.
AB  - 5-Fluorouracil (5FU) exposure can lead to both G1/S arrest and apoptosis
      induction which are dependent of P53 induction. The human papilloma virus
      oncoproteins (HPV), E6 and E7, inactivate respectively P53 and Rb. P53
      degradation by E6 protein, leads to lack of G1/S arrest after genotoxic stress.
      Overexpression of E7 protein prevents P53-induced G1/S arrest following DNA
      damage. However, few studies have described 5FU effect and efficacy on cancer
      cell lines presenting HPV 18 positive status. KB cell line and KB3 subline
      presented wild-type P53 status and difference in 5FU sensitivity. During 5FU
      exposure, P53 gene and protein expression was increased in both cell lines. E6
      and E7 mRNA and protein expression was decreased in KB and KB3. P53 and E6
      protein expressions were inversely correlated. 5FU exposure, induced a G1/S
      arrest which can be maintained or intensified by P53 via P21 induction
      expression. 5FU exposure has led to apoptosis induction related to P53 induction.
      In the present study, 5FU exposure was shown to induce G1/S arrest and apoptosis
      by P53-dependent molecular pathway, in HPV 18 positive cells.

PMID- 12792780
TI  - Differential expression and regulation of bone morphogenetic protein 7 in breast
      cancer.
AB  - Bone morphogenetic protein 7 (BMP-7) is an important regulator of cell
      development and differentiation of various organs. Tumorigenesis and tumor
      progression are also strongly associated with changes of the fate of cells which
      are highly differentiated in healthy tissues. Therefore, we studied the role of
      BMP-7 in breast cancer cell lines and in breast tumor tissue samples. BMP-7 is
      expressed in various cell lines, but in a cell line specific manner. The breast
      cancer cell lines MCF-7 and SK-BR-3 showed BMP-7 expression on the mRNA level. In
      T-47D we were not able to detect BMP-7 on the mRNA but on the protein level.
      Additionally, epidermal growth factor (EGF), a stimulator of proliferation, was
      not able to enhance BMP-7 expression on the transcriptional level. These findings
      are in contrast to the EGF-dependent regulation of BMP-6, indicating a
      differential regulation of these closely related TGF-beta members. In order to
      confirm the data obtained from cell cultures, we analyzed normal breast tissue
      and tumor tissue samples from 170 invasive ductal carcinomas of the breast by
      immunohistochemistry. We found BMP-7 expression in normal breast tissue in the
      end buds, but not in the ductus lactiferus. BMP-7 protein was detected in all 170
      tumor samples. Comparing BMP-7 levels with histopathological parameters, we could
      not show a correlation of BMP-7 and the proliferation index nor with erbB
      receptors. But the expression of BMP-7 was highly correlated with estrogen
      receptor levels (p< or=0.01) and progesterone receptor levels (p< or =0.01) which
      are important markers for breast cancer prognosis and therapy.

PMID- 12792781
TI  - Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the
      nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma.
AB  - Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically
      mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is
      known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA
      array technology, we wanted to document its phenotypical and molecular
      characteristics. We report herein 5 cases of UCNT that morphologically mimic HL
      and 3 classical UCNT cases. We compared the expression profiles of a thousand
      selected genes in HL-like UCNT and in classical UCNT cases. No difference in the
      profile of EBV infection was noted between the HL-like UCNT and control cases.
      Significant differences were detected in the expression of genes involved in the
      matrix modelling, angiogenesis, apoptosis and regulation of the Th-2
      interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma
      of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was
      expressed in both stromal and carcinoma cell populations of HL-like UCNT, this
      pattern being similar to the one observed in HL. These results show that UCNT
      morphologically resembling HL share also some specific phenotypical and molecular
      features with HL, and might deserve to be isolated as a particular UCNT subtype.

PMID- 12792782
TI  - Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest
      in HaCat cells.
AB  - Ursolic acid (UA) is a pentacyclic triterpene compound isolated from many kinds
      of medicinal plants and present in human diet. In this study, we investigated the
      pro-apoptotic effect of UA on HaCat derived keratinocyte cell line. Treatment
      with UA decreased the viability of HaCat cells in a concentration- and time
      dependent manner. In addition, cell cycle analysis revealed that UA treated HaCat
      cells were blocked predominantly in G1 phase. Moreover, expression of p21WAF1, a
      cell cycle regulator, was increased by UA, indicating that UA-induced cell cycle
      arrest could be mediated through p21WAF1. During UA treatment, we also
      demonstrated that p53 was phosphorylated at serine 392 and translocated to the
      nucleus. It is well established that p53 achieves its tumor suppressor activity
      by inducing apoptosis on cells. To define the apoptotic process in our system, we
      examined effect of UA on caspase activities, and demonstrated caspase-3
      activation. In conclusion, our results suggest that UA induces: i) cell cycle
      arrest concomitantly with the apparition of the apoptotic sub group G1 peak, and
      ii) cell death through apoptosis, which is mediated by caspase-3.

PMID- 12792783
TI  - Specific COX-2 inhibitor, NS-398, suppresses cellular proliferation and induces
      apoptosis in human hepatocellular carcinoma cells.
AB  - Cyclooxygenase (COX-2) has been recently suggested to play a role in
      hepatocarcinogenesis. However, the exact pathway by which COX-2 affects the
      growth of hepatocellular carcinoma (HCC) is not clear. This study investigated
      the effects of a specific COX-2 inhibitor, NS-398, on the cell proliferation and
      apoptosis of COX-2-expressing and non-expressing HCC cell lines. In addition, the
      modulatory effect of NS-398 on apoptosis-regulating gene expression was examined.
      Semi-quantitative/quantitative reverse transcription-polymerase chain reaction
      and Western blot showed that Hep3B and HKCI-4 cells expressed COX-2 mRNA and
      protein, but HepG2 cells did not. NS-398 suppressed cell proliferation and
      induced apoptosis in the two COX-2-expressing cell lines in a dose-dependent
      manner, but not in HepG2 cells. Fas ligand mRNA and protein expression were
      increased by the treatment with NS-398 (10 micro M) in COX-2-expressing cell
      lines. The expressions of Fas and Bcl-2 family genes (Bax, Bcl-2, Bcl-xL, Bcl-xS)
      were not affected by NS-398 treatment in all three cell lines. In conclusion,
      specific COX-2 inhibitor suppresses cell proliferation and induces apoptosis in
      HCC cell lines that express COX-2. Our finding suggests that COX-2 inhibition may
      offer a new approach for HCC chemoprevention.

PMID- 12792784
TI  - High frequency of temperature-sensitive mutations of p53 tumor suppressor in
      acute myeloid leukemia revealed by functional assay in yeast.
AB  - The tumor suppressor p53 is a transcription factor that participates in control
      of many cellular functions. All these activities are mediated by direct binding
      of the p53 tetramer to specific target sequences in promoters of directed genes.
      Lack of p53 function is often connected with development of cancer, but the
      frequency of p53 mutations is low in almost all types of leukemia. The aim of
      this study was to assess the frequency of mutations in the p53 gene in leukocytes
      of patients with acute myeloid leukemia (AML) using the FASAY functional analysis
      and to assess the relationship between the presence of p53 mutation and disease
      outcome. The following observations were made: i) the presence of p53 mutations
      was detected in 13 of 62 tested AML cases (21%) and in 1 of 4 tested
      myelodysplastic syndrome (MDS) cases by FASAY; ii) the presence of p53 mutation
      was shown to be a poor prognostic/predictive factor in AML (p=0.03/0.002); iii)
      although there is a statistically significant relationship between the presence
      of p53 mutation and p53 protein accumulation (p=0.05), not all samples having p53
      mutation exhibited p53 protein accumulation; iv) five of 13 p53 mutations
      detected in the leukocytes of AML patients (38.5%) and the mutation detected in
      the leukocytes of the MDS patient (altogether 6/14-42.9%) were partially
      inactivating ts mutations. The high frequency of the ts p53 mutations in our
      study; and a novel modification in performing FASAY, are discussed; v) different
      ts mutations differ in the level of their temperature sensitivity and in their
      responsiveness to the cytoprotective drug amifostine.

PMID- 12792785
TI  - DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular
      carcinoma.
AB  - The DLC-1 gene encoding a regulator of the Rho family of small GTPases is altered
      in breast, prostate, colon, and liver cancer and has several characteristics of a
      tumor suppressor gene. DLC-1 overexpression causes inhibition of in vitro growth
      of liver tumor cells and complete suppression of in vivo tumorigenicity of breast
      tumor cells. Inactivation and aberrant expression of DLC-1 in human
      hepatocellular carcinoma (HCC) is frequently associated with hemizygous and
      homozygous genomic deletion and promoter methylation. Since inactivation of tumor
      suppressor genes in cancer cells is also commonly associated with point mutation,
      we evaluated the incidence of mutation of the DLC-1 gene by PCR-SSCP in 17
      primary HCC and 18 HCC cell lines. One missense mutation was detected at codon
      991 of exon 12 (C-->T transition, Val-->Ile) in an HCC cell line. In addition,
      two types of polymorphisms were identified: a G-->T at codon 745 of exon 9, a T-
      >C at 17 bp downstream of exon 2. While the pathogenic relevance of the intronic
      polymorphism is not known, the low rate of mutation of the DLC-1 gene in HCC
      implies that genomic deletion and promoter methylation primarily account for the
      altered expression and tumor suppressive inactivation of the DLC-1 gene.

PMID- 12792786
TI  - Highly complex karyotypic changes in acute myelogenous leukemia: a case report.
AB  - We report on a patient with a clinically diagnosed acute myelogenous leukemia
      (AML) with so far unrecorded complex translocations. As GTG-banding was not able
      to resolve all karyotypic changes, spectral karyotyping (SKY) and multiplex
      fluorescence in situ hybridization (M-FISH) were performed for comparison. Both
      methods gave nearly identical results, however, they were unable to characterize
      all involved chromosomal breakpoints in detail. Thus, multicolor banding (MCB)
      technique was applied and its results were confirmed for two large derivative
      chromosomes by microdissection and reverse painting. Using this battery of
      molecular cytogenetic approaches the karyotype of this AML case could be
      described as 40 approximately 44,XY,der(1)t(1;5;8;20) (1qter-->1p12::5q14.3-
      >5q15 or 5q15-->5q14.3::8p11.2-->8p23.? 3::20p11.1-
      >20p13),del(2)(q12),der(3)t(3;6),der(5)t(5;18) (5p15.33-->5q11::18q21.3-
      >18q23),del(6),-8,der(9)t(9;17;15),der(10)t(3;10),del(11)(q24),-15,
      16,del(17),der(18) t(8;18;5;2;20)(8q24.3-->8q24.2 or 8q24.2-->8q24.3::18p11.22-
      >18q21.3::5q14.3-->5q11::2q32-->2q12::20q13.2-->20q13.33),
      der(20)t(1;20;18)(1p36.33-->1p31.3-22.3::20p11.1-->20q11.2 or 20q11.2-
      >20p11.1::18p11.22-->18p11.32).

PMID- 12792787
TI  - KIAA1735 gene on human chromosome 11q23.1 encodes a novel protein with myosine
      tail homologous domain and C-terminal DIX domain.
AB  - Dishevelled 1 (DVL1), DVL2 and DVL3 are DIX-domain proteins implicated in the WNT
      signaling pathway. Here, we searched for a novel DIX-domain protein by using
      bioinformatics. Uncharacterized human KIAA1735 gene was found encoding a novel
      DIX-domain protein. Mouse ortholog of human KIAA1735 gene was next identified,
      and the nucleotide sequence of mouse Kiaa1735 cDNA was determined in silico by
      assembling nucleotide sequences of ESTs BY753211, BQ931084, CA750490, BQ960056
      and a 5'-truncated partial cDNA AK082960. Human KIAA1735 protein (472 aa) and
      mouse Kiaa1735 protein (474 aa) showed 90.9% total-amino-acid identity. Myosine
      tail homologous (MTH) domain and C-terminal DIX domain were conserved between
      human KIAA1735 and mouse Kiaa1735 proteins. A tyrosine phosphorylation site (Tyr
      242) within the MTH domain was conserved between human KIAA1735 and mouse
      Kiaa1735 proteins. Leucine zipper motif (codon 202-237) and another tyrosine
      phosphorylation site (Tyr 272) were identified within the MTH domain of human
      KIAA1735, but not within that of mouse Kiaa1735. Human KIAA1735 mRNA was
      expressed in brain, subchondral bone, and also in lung cancer. KIAA1735 gene,
      consisting of 16 exons, was about 45 kb in size. KIAA1735 gene was linked to DLAT
      gene in tail-to-head manner with an interval less than 4.0 kb. KIAA1735 gene on
      human chromosome 11q23.1 was located between D11S1391 and D11S1347 loci, the
      region deleted in sporadic breast cancer. This is the first report on
      comprehensive characterization of the KIAA1735 gene.

PMID- 12792789
TI  - Protection against Adriamycin cytotoxicity and inhibition of DNA topoisomerase II
      activity by 3,4-dihydroxybenzoic acid.
AB  - The mechanism of Adriamycin (ADR) induced cytotoxicity is not completely
      understood. While a variety of mechanisms have been proposed, the production of
      free radicals by redox cycling of the semiquinone has been implicated in
      cytotoxicity, specifically for cardiotoxicity. To determine whether a scavenger
      of free radicals would modify the cytotoxicity of ADR, the benzoic acid
      derivative 3,4-dihydroxybenzoic acid (DHB) was investigated for its ability to
      protect against ADR-induced cytotoxicity and DNA double strand breaks in Chinese
      hamster V79 cells. V79 cells were treated with ADR, or its non-redox cycling
      analog iminodaunomycin, in the presence or absence of DHB. DHB provided
      significant protection (dose-modifying factor greater than 2.5 for ADR, and
      nearly 2 for iminodaunomycin) and also caused a dose-dependent decrease in DNA
      double strand breaks as measured by pulsed field gel electrophoresis. Assays of
      topoisomerase II activity showed that DHB inhibited topoisomerase II in a
      concentration-dependent manner, but did not inhibit topoisomerase I. Another non
      toxic topoisomerase II inhibitor, the radioprotector WR-1065, also protected
      against ADR-induced cytotoxicity. These data identify DHB as a non-toxic
      inhibitor of DNA topoisomerase II and suggest that much of the cytotoxicity of
      ADR in actively growing V79 cells is due to mechanisms other than redox cycling
      by the semiquinone.

PMID- 12792788
TI  - Synergistic growth inhibitory effects of interferon-alpha and lovastatin on bcr
      abl positive leukemic cells.
AB  - The chimeric bcr-abl tyrosine kinase is of crucial pathogenic importance in
      chronic myeloid leukemia (CML). As shown, bcr-abl activates the ras pathway by
      phosphorylation of adapter proteins such as Grb-2 and Crkl. Functional inhibition
      of p21ras might partially inhibit the mitogenic signaling by bcr-abl. By
      depletion of cellular mevalonate pools, p21ras proteins can be rendered non
      functional as a result of deficient post-translational protein farnesylation. We
      investigated the pharmacologic effect of mevalonate depletion by lovastatin in
      conjunction with interferon-alpha 2b (INF-alpha 2b) in bcr-abl positive K562
      cells. At various concentrations, both drugs synergistically reduced cell
      proliferation of CML line K562 in a liquid culture system as well as clonal
      growth of colony forming units in a patient with newly diagnosed CML. Lovastatin
      and IFN-alpha 2b in combination led to cell cycle arrest and resulted in
      significant reduction of phosphorylation on tyrosine, serine, and threonine
      protein residues. IFN-alpha 2b alone showed little effect on protein
      phosphorylation but strongly enhanced lovastatin driven loss of phosphorylation.
      Subsequently, DNA fragmentation occurred in 50% of cells. In conclusion, exposure
      to IFN-alpha 2b and lovastatin synergistically inhibited proliferation of bcr-abl
      positive cells and resulted in loss of protein phosphorylation and subsequent
      apoptosis in K562 cells. Our in vitro model suggests further investigations are
      required of the potential value of HMG-CoA reductase inhibitors as adjunct to
      therapy of CML with interferon.

PMID- 12792790
TI  - A randomized controlled trial of postoperative adjuvant immunochemotherapy for
      colorectal cancer with oral medicines.
AB  - Postoperative adjuvant chemotherapy reportedly improves advanced colorectal
      cancer patients' survival, however, it is necessary to assess what regimens are
      useful. Doxifluridine (5'-DFUR) is an intermediate of capecitabine approved in
      Europe and USA to treat metastatic colorectal cancer. 5'-DFUR is metabolized to 5
      fluorouracil (5-FU) by thymidine phosphorylase existing in tumor at high
      concentrations, suggesting high 5-FU levels in tumor tissues and lesser
      complications. Present study compared usefulness of 5'-DFUR to that of oral 5-FU.
      Patients were enrolled at 38 centers from April 1993 to September 1996. They had
      diagnosed colorectal cancer of TNM stages II and III, and underwent macroscopic
      curative resection. Patients were prestratified into colon or rectum cancer and
      allocated into either 5'-DFUR (5'-DFUR 460 mg/m(2)/day + PSK 3 g/day) or 5-FU (5
      FU 115 mg/m(2)/day + PSK 3 g/day) group by dynamic randomization (stratification
      factors such as depth of tumor, degree of lymph node metastasis, and location of
      tumor). Drugs were orally administered daily from postoperative week 2 to 54,
      with 6 mg/m(2) mitomycin C at operation and following days. Subjects for analysis
      were 277 in 5'-DFUR and 281 in 5-FU groups. Median follow-up was 6.5 years.
      Although no differences in overall survival curves were detected, multivariate
      analysis showed that 5'-DFUR + PSK regimen was a significantly better prognostic
      factor in patients with Dukes B or C (risk ratio, 1.451; p=0.048); with tumor
      depth of pT3 or pT4 (risk ratio, 1.568; p=0.020). For patients with advanced
      colorectal cancer, 5'-DFUR + PSK therapy may possibly be more useful than 5-FU +
      PSK, but further study is required.

PMID- 12792791
TI  - Overexpression of mutated MRP4 in cisplatin resistant small cell lung cancer cell
      line: collateral sensitivity to azidothymidine.
AB  - Cisplatin (CDDP) resistance is one of the major impediments in cancer
      chemotherapy. In an attempt to define this complex mechanism(s) of resistance, we
      have identified 7 cDNA fragments which are overexpressed in CDDP resistant small
      cell lung cancer cell line (SR-2) using PCR selected cDNA subtraction. One of
      these fragments was identical with nucleotide 3657-4042 of MRP4. The other
      fragments share sequence homology with elongation factor alpha, human placenta
      villi cDNA, heat shock protein (Hsp70), ribosomal RNA, BNP1 brain specific Na
      dependent inorganic phosphate cotransporter and telomeric catalytic subunit.
      Examination of other MRP members (MRP1, 2, 3, 5, 6) did not show discernable
      differences in their expression between the parental (SCLC1) and the CDDP
      resistant variant (SR-2). Full length MRP4 cDNA was obtained from SCLC1 and SR-2.
      Both cell lines carry a point mutation at nucleotide 3532 while SR-2 carries two
      additional mutations at 3228 and 3246. Since MRP4 is known to transport
      azidiothymidine (AZT) and overexpression of MRP4 confers AZT resistance, we have
      studied growth inhibitory effects of AZT and [3H]-AZT accumulation.
      Interestingly, SR-2 is more sensitive to AZT while accumulating lesser amounts of
      [3H]-AZT. The thymidine kinase activity is similar in both cell lines. Thus, the
      increased sensitivity to AZT in SR-2 could not be solely due to mutation of MRP4.
      These findings are most likely due to the inhibitory effects of telomere
      catalytic subunit by AZT. Thus, certain biochemical changes induced by CDDP can
      be explored for future treatment to overcome this form of resistance.

PMID- 12792792
TI  - All trans retinoic acid sensitizes colon cancer cells to hyperthermia cytotoxic
      effects.
AB  - The effects of all trans retinoic acid and hyperthermia were studied in the human
      colon adenocarcinoma cell line HT29. Cell cytotoxicity after exposure to ATRA or
      heat-shock, alone or in association, was evaluated by the MTT assay while cell
      surface and ultrastructure modifications and actin fibre assembly changes were
      investigated by electron microscopy and by the FITC-phalloidin method. Apoptosis
      was evaluated by flow cytofluorimetry and electron microscopy. Reverse
      transcriptase-polymerase chain reaction was employed to study mRNA expression of
      genes involved in apoptosis, differentiation and growth arrest. Joint treatments
      were more effective in reducing the vital cell yield, being this effect only
      partially due to apoptosis. A marked up-regulation of the cyclin-dependent kinase
      inhibitor p21WAF1/Cip1 expression, not followed by any differentiation process,
      was responsible for growth arrest. Modulation of Hsp-70 expression, involved in
      cell response to treatments, was considered. Our results demonstrate that cell
      treatment with ATRA followed by heat-shock may elicit useful effects to treat
      tumours, which are responsive to retinoids, as well as those malignant cells
      which may be constitutively thermotolerant.

PMID- 12792793
TI  - TP53 mutations in primary breast carcinomas from white and African-Brazilian
      patients.
AB  - We have attempted to determine the incidence, nature and clinical significance of
      TP53 mutation in a group of white (242 cases) and African-Brazilian (52 cases)
      patients with breast cancer. The interethnic admixture as estimated by STR
      markers showed that white subjects displayed 67.9+/-0.4%, 25.0+/-1.7% and 7.0%+/
      1.6% and the black populations had 34.4+/-1.9%, 56.2+/-1.9 and 9.4+/-2.2%
      respectively of European, African and Amerindian genes. Clinical parameters such
      as age, lymph node status and steroid receptors were similar in both groups.
      African-Brazilian patients presented more advanced lesions. Mutation screening
      was performed using polymerase chain reaction-single strand conformation analysis
      followed by sequencing. Compared to whites (13.6%), a relatively high frequency
      of TP53 mutation was found in blacks (32.7%) (p=0.001). African-Brazilian women
      have a larger proportion of mutations in exons 5 and 7, whereas white women have
      more mutations in exon 8. Mutations within exon 4 were found only in tumors of
      white patients. The spectra of TP53 mutations show that A:T-->G:C nucleotide
      transversion and G:C-->C:G transition were more common in African-Brazilian women
      whereas G:C-->T:A transversion occurs very frequently in whites. A high
      prevalence of G:C-->A:T nucleotide transitions and deletions was detected in both
      groups. No association was found between p53 gene mutation and tumor or clinical
      parameters independently of the ethnic group. With a median follow-up of 35.6
      months for whites and 43.4 months for the blacks, no differences in overall
      survival were found. If white patients were stratified according to the type and
      location of TP53 mutations, patients with mutations affecting amino acids
      directly involved in DNA or Zn binding displayed a poor prognosis. The pattern of
      mutations found in our population seems to reflect a base line pattern observed
      in populations with similar ethnic profile with some modifications, which might
      be derived from specific etiological factors.

PMID- 12792794
TI  - Monensin-mediated growth inhibition in NCI-H929 myeloma cells via cell cycle
      arrest and apoptosis.
AB  - Previously, we showed that monensin, Na+ ionophore, potently inhibited the growth
      of acute myelogenous leukemia and lymphoma cells. Here, we investigated the
      antiproliferative effect of monensin on human myeloma cell lines. Monensin
      significantly inhibited the proliferation of myeloma cell lines examined with
      IC50 of about 1 micro M. Cell cycle analysis indicated that monensin induced a G1
      and/or a G2-M phase arrest in these cell lines. To address the mechanism of the
      antiproliferative effect of monensin, we examined the effect of this drug on cell
      cycle-related proteins in NCI-H929 cells. Monensin decreased the levels of CDK2,
      CDK6, cdc2, cyclin A, cyclin B1, cyclin D1 and cyclin E proteins but did not
      alter CDK4 protein. While p21 was increased by monensin, p27 was not. In
      addition, monensin markedly enhanced the binding of p21 with CDK6 and cdc2.
      Furthermore, the activities of CDK2- and CDK6-associated kinases were reduced in
      association with hypophosphorylation of Rb protein. The activity of cdc2
      associated kinase was decreased, which was accompanied by reduction of cdc25C
      phosphatase. Also, monensin induced apoptosis in myeloma cells, as evidenced by
      annexin V binding assay and flow cytometric detection of sub-G1 DNA content. This
      apoptotic process was associated with down-regulation of Bcl-2, loss of
      mitochondria transmembrane potential (Deltapsim) and an increase of caspase-3
      activity. In addition, monensin caused the up-regulation of ERK and p38 kinase
      activities. Taken together, these results have demonstrated for the first time
      that monensin potently inhibited the proliferation of human myeloma cell lines,
      especially NCI-H929 cells, via cell cycle arrest in association with p21 and
      apoptosis.

PMID- 12792795
TI  - Effects of apoptosis-inducing nucleosides released from CD57+HLA-DRbright natural
      suppressor cell line on human breast cancer cell death and growth.
AB  - The CD57+HLA-DRbright-natural suppressor (57.DR-NS) cell line induced apoptosis
      in estrogen-non-responsive human breast carcinoma MDA-MB-435 cells by apoptosis
      inducing nucleosides (AINs) released into the cultures. We obtained six active
      AINs isolated by high performance liquid chromatography (HPLC) from 57.DR-NS cell
      cultures. Each AIN isolated from 57.DR-NS cell cultures induced apoptosis in MDA
      MB-435 cells. We found the occurrence of DNA strand breaks followed by the
      activation of caspase-3 during AIN-induced apoptosis in MDA-MB-435 cells. The
      data obtained here indicated that 57.DR-NS cells could induce apoptosis in MDA-MB
      435 cells mediated by AINs through DNA strand breaks and activation of caspase-3.
      Furthermore, the administration of AINs into MDA-MB-435 tumor-bearing SCID mice
      culminated in strong suppression of tumor growth with no change of body weight of
      experimental mice suggesting no side effects of AINs.

PMID- 12792796
TI  - Evaluation of MDR1, LRP, MRP, and topoisomerase IIalpha gene mRNA transcripts
      before and after interferon-alpha, and correlation with the mRNA expression level
      of the telomerase subunits hTERT and TEP1 in five unselected human melanoma cell
      lines.
AB  - Intrinsic and acquired multidrug-resistance (MDR) and the activity of the enzyme
      telomerase have been demonstrated in human melanoma. A direct regulation of the
      MDR pathways and of telomerase by interpheron-alpha (IFN-alpha), which is
      currently used in the therapy of advanced cutaneous melanoma, has also been
      hypothesized. In this study, we used five melanoma cell lines not selected in
      vitro for drug resistance (Me665/2/21, Me665/2/60, HT-144, SK-MEL-28, and SK-MEL
      5), which in a previous study, had shown different responses to IFN-alpha in
      terms of proliferation, apoptosis, telomerase activity and expression of mRNA for
      the human telomerase reverse transcriptase (hTERT). We investigated the
      expression of the multidrug resistance (MDR1) gene, multidrug resistance protein
      (MRP), lung resistance protein (LRP), topoisomerase IIalpha (Topo IIalpha),
      hTERT, and telomerase-associated protein (TEP1), which is shared by telomerase
      and vault MDR proteins at the mRNA expression level, using the reverse
      transcription-PCR (RT-PCR). All cell lines showed an intrinsic expression of
      hTERT, TEP1, and MDR gene transcripts (only MDR1 mRNA was under the detection
      level in SK-MEL-28 cells). After IFN-alpha exposure, we observed either no
      effect, a trend towards a decrease of hTERT, MRP, and Topo IIalpha, or an
      increase of TEP1, MDR1, and LRP mRNA expression in some cell lines. Effects were
      usually temporary and not always significant. No correlation was found between
      hTERT and TEP1 mRNA expression, whereas significant positive correlations were
      found between TEP1 and MDR1 mRNA, and between TEP1 and LRP mRNA. IFN-alpha
      modulates differently MDR gene transcripts in human melanoma cell lines. Positive
      correlation between TEP1 and LRP also seems to identify them as common targets of
      IFN-alpha effects.

PMID- 12792798
TI  - WD-40 repeat containing rat lethal giant larvae recessive oncogene, but not m
      tomosyn, restores the salt sensitivity in Saccharomyces cerevisiae.
AB  - Recently, we cloned rgl-1, a putative rat homologue of the Drosophila tumor
      suppressor oncogene lethal (2) giant larvae (l(2)gl), from the rat brain.
      Sequence analysis revealed that rgl-1 encodes a 1,036 amino acid polypeptide
      containing a domain characteristic of WD-40 repeat sequence. It has been
      suggested that m-tomosyn is expressed in the rat brain, encodes a 1,116 amino
      acid polypeptide, contains WD-40 repeat sequence, and is homologous to the
      Drosophila l(2)gl and mouse mgl-1 genes. The comparison of amino acid sequence
      for m-tomosyn with l(2)gl and mgl-1 proteins using the clustal method showed only
      17.8% and 20% amino acid identity, respectively. However, amino acid identity of
      rgl-1 protein to l(2)gl and mgl-1 proteins is much higher (30.6% and 96.8%,
      respectively). Therefore, we investigated their biological function in the
      absence of Saccharomyces cerevisiae SOP1 and SOP2, the yeast homologues of the
      Drosophila l(2)gl. Functional analysis showed that the expression of the rgl-1
      cDNA, but not m-tomosyn, restored partially salt sensitivity in yeast, indicating
      that rgl-1 is a homologue of lgl family members.

PMID- 12792797
TI  - Multiple tumor marker analyses (PSA, hK2, PSCA, trp-p8) in primary prostate
      cancers using quantitative RT-PCR.
AB  - The identification of new diagnostic markers and potential treatment targets for
      prostate carcinoma (PCa) necessitates the evaluation of expression patterns in
      both malignant and non-malignant tissue specimens. In this study, we compared the
      mRNA expression of recently identified prostate-associated genes, prostate stem
      cell antigen (PSCA) and transient receptor potential p8 (trp-p8), to the mRNA
      expression of the most commonly used markers for PCa, prostate-specific antigen
      (PSA) and human kallikrein 2 (hK2). For these four candidates we performed highly
      specific quantitative real-time LightCycler RT-PCR assays with cDNA originating
      from matched tissue specimens of 40 patients with primary PCa. The highest
      transcript amounts were found for PSA in malignant as well as in non-malignant
      tissue specimens followed by hK2, trp-p8 and PSCA with an mRNA expression
      remarkably lower. The relative transcript levels of PSA, hK2 and trp-p8 were
      elevated in malignant in comparison to non-malignant tissues, but only for trp-p8
      this increased expression was statistically significant. Focussing on organ
      confined tumors, we found a significant difference of the mRNA expression of PSA
      and trp-p8 between malignant and non-malignant tissue specimens. The marker trp
      p8 is also suited to differentiate between the tumor stages when quantifying its
      transcript levels within tumor tissue specimens. The evaluation of the mRNA
      expression patterns of these markers by quantitative real-time RT-PCR could
      provide new tools for differential diagnosis and molecular staging. According to
      our data, the novel marker trp-p8 seems to represent a highly prostate-specific
      and PCa-associated gene qualifying it as a potential target for specific
      therapies.

PMID- 12792799
TI  - MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer,
      encodes secreted-type protein with conserved cysteine residues.
AB  - Microarray analyses is applied for prognosis of gastric cancer, including risk
      assessments of lymph-node metastasis and peritoneal dissemination. EST AA769445
      derived from an unknown gene is reported to be frequently down-regulated in
      intestinal-type gastric cancer based on microarray analyses. Here, we identified
      and characterized the gene corresponding to EST AA769445 by using bioinformatics.
      EST AA769445 overlapped with MGC29506 cDNA (BC021275) and PACAP cDNA (AF338109).
      MGC29506 protein (189 aa) and PACAP protein (123 aa) were identical in codon 1
      59, but were divergent in the C-terminal region due to a frame shift caused by
      sixteen-base insertion in PACAP cDNA. MGC29506 and PACAP were derived from the
      same gene, consisting of four exons, due to alternative splicing of alternative
      splice-acceptor-site type. Fourteen human ESTs were the MGC29506 type, while one
      human EST was the PACAP type. MGC29506 was the major isoform of the
      MGC29506/PACAP gene on human chromosome 5q31.2. MGC29506 orthologs in other
      species were next searched for. AK088094 and AK008016 cDNAs with nucleotide
      substitutions resulting in four-amino-acid substitutions were derived from mouse
      Mgc29506 gene. Rat Mgc29506 gene was identified in the rat genome draft sequence
      AC135285. ESTs AJ396310 and AJ441435 were derived from chicken Mgc29506 gene,
      while ESTs BW315632 and BW251767 from ciona mgc29506 gene. N-terminal signal
      peptide, six cysteine residues and other amino acids were conserved among human,
      mouse, rat, chicken, and ciona MGC29506 proteins. MGC29506 gene, frequently down
      regulated in intestinal-type gastric cancer, was found to encode secreted-type
      protein with six conserved cysteine residues.

PMID- 12792800
TI  - Prophylactic, therapeutic and anti-metastatic effects of BMDC and DC lines in
      mice carrying HPV 16-associated tumours.
AB  - Oncogenic, moderately immunogenic MK16/1/IIIABC (MK16) cells were previously
      established by co-transfection of HPV 16 E6/E7 and activated H-ras oncogene DNA
      into C57BL/6 kidney cells. Subcutaneous transplantation of the MK16 cells
      produced progressively growing neoplasms which metastasized spontaneously to
      lungs. In this communication we report that prophylactic administration of bone
      marrow-derived dendritic cells (BMDC) as well as dendritic cell (DC) lines DC2.4
      and JAWS II at the site of subsequent MK16 tumour transplants inhibited tumour
      growth and reduced the number of lung metastases. Similarly, in therapeutic
      experiments, administration of BMDC and DC lines at the site of the growing MK16
      tumours or at the site of MK16 tumour residua after surgery inhibited tumour
      growth. Both BMDC-based vaccines and vaccines based on DC lines had also an
      antimetastatic effect. These results indicate that the DC line-based vaccines,
      which represent a standard, well-characterized and more homogeneous material,
      technically easier to prepare than the fresh BMDC-based vaccines, can be utilized
      for therapy of surgical minimal residual disease in HPV 16-associated neoplasms
      and are prospective for relevant clinical trials.

PMID- 12792801
TI  - Trefoil factors and human gastric cancer (review).
AB  - TFF1/pS2, TFF2/SP and TFF3/ITF are soluble peptides with trefoil domain(s) and C
      terminal dimerization domain, which are conserved among human, cow, mouse and
      rat. TFF1 mRNA is expressed in stomach (mucous cells in fundus and antrum), TFF2
      mRNA in stomach (mucous neck cells in fundus and basal cells in antral and
      pyloric glands) and duodenum (Brunner's gland), TFF3 mRNA in small intestine and
      large intestine (goblet cells). Expression of TFF1, TFF2 and TFF3 mRNAs are
      differentially regulated by FGF2/bFGF, FGF7/KGF, estrogen, aspirin, arachidonic
      acid, X-ray irradiation, and hydrogen peroxide. Gastric cancer is classified into
      the intestinal type and the diffuse type. TFF mRNAs are preferentially expressed
      in diffuse-type gastric cancer cells. Custom-made microarray (TFF mRNAs) and
      ELISA (TFF proteins) might be applicable for screening methods of peritoneal and
      bone marrow dissemination from diffuse-type gastric cancer. TFF1 and TFF2 mRNAs
      are frequently down-regulated in intestinal-type gastric cancer. TFF1 gene,
      inactivated by deletion, missense mutation and promoter hypermethylation, is a
      tumor suppressor gene implicated in gastric cancer. TFF2 is a candidate tumor
      suppressor gene; however, genetic and epigenetic alterations of TFF2 gene in
      human gastric cancer remain unclear. TFF1, TFF2 and TFF3 play key roles in
      mucosal protection through mucous-barrier formation, and also in mucosal repair
      through promotion of restitution after injury. Patients with chronic atrophic
      gastritis and those with ulcerative colitis are at risk of gastric cancer and
      colorectal cancer, respectively. TFF1, TFF2 and TFF3 proteins might be applicable
      for chemoprevention of gastrointestinal cancer associated with chronic persistent
      inflammation.

PMID- 12792802
TI  - The transmembrane domain of vesicular stomatitis virus glycoprotein suffices to
      anchor HIV-1 envelope gp120 expressed by a recombinant vaccinia virus.
AB  - The shedding of HIV-1 glycoprotein gp120 results from the proteolytic cleavage of
      its precursor gp160 into gp120 and an anchoring gp41, to which gp120 is non
      covalently attached. This report is directed toward the anchorage of gp120
      expressed by three recombinant vaccinia virus (rvv): vPE16 expresses wild-type
      gp160; vvE13 the gp120-vesicular stomatitis virus G transmembrane and cytoplasmic
      tail (VSVGTMCT) fusion protein; and vvE14 the gp120 with 52 amino acids (aa) from
      the vector. In order to convert gp120 into an integral membrane protein, a gp120-
      VSVGTMCT chimerical gene fragment has been constructed and expressed in mammalian
      cells. This gp120 fusion protein expressed by an rvv, vvE13, has been shown to
      elicit better immunogenicity and protection against a gp160-expressing tumor cell
      line than the full-length envelope (env) glycoprotein gp160 in mice. The results
      show that gp120-VSVGTMCT expressed by vvE13 is not shed because it is membrane
      associated. The hydrophobic fragment of vesicular stomatitis virus G (VSVG)
      furnishes an anchor of the chimeric protein just as it does in the native VSVG.

PMID- 12792803
TI  - Structure of curcumin in complex with lipoxygenase and its significance in
      cancer.
AB  - Scientific research provides documented evidence that fatty acid metabolites have
      profound impact on carcinogenesis. Intervention into dioxygenase pathways might
      therefore effect development, metastasis and progression of many types of
      cancers. This work delivers the first 3D structural data and explains how
      curcumin interacts with the fatty acid metabolizing enzyme, soybean lipoxygenase.
      Curcumin binds to lipoxygenase in a non-competitive manner. Trapped in that
      complex, it undergoes photodegradation in the X-rays, but utilizes enzyme
      catalytic ability to form the peroxy complex Enz-Fe-O-O-R as 4-hydroperoxy-2
      methoxy-phenol, that later transforms into 2-methoxycyclohexa-2,5-diene-1,4
      dione. Our observations about this radiation and time-dependent inhibition add
      new information to the role that curcumin might play in cancer prevention and
      treatment.

PMID- 12792804
TI  - Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular
      carcinoma.
AB  - The second mitochondria-derived activator of caspase, Smac, is an apoptosis
      related protein. Smac releases inhibition of the IAP family from caspase-3 to
      induce apoptosis. Smac is expressed in some malignant tumor cells and is released
      from mitochondria into the cytosol after death receptor stimulation to promote
      apoptosis of tumor cells. In this study, we found down-regulated Smac protein
      expression in hepatocellular carcinoma (HCC) tissues, compared to that in non
      tumor hepatic tissues. Simultaneously, caspase-3 expression also decreased in HCC
      tissues. HCC cell lines did not undergo apoptosis after TRAIL stimulation,
      although Smac was expressed in these HCC cells. Ectopic Smac alone did not induce
      cell death, but could sensitize HCC cells to TRAIL stimulation. With over
      expression of Smac in HCC cells, TRAIL induced by 10% HCC cell death. The role of
      Smac in apoptosis signaling pathway in HCC cells warrants further study.

PMID- 12792805
TI  - Pleotropic effects of genistein on MCF-7 breast cancer cells.
AB  - Soy isoflavone, genistein has been shown to induce growth inhibition, cell cycle
      arrest and apoptosis in cultured cancer cell lines derived from head and neck,
      breast, lung, and prostate cancers and showed antitumor activity against tumors
      in multiple animal models. In the present study we show that genistein inhibits
      the growth of MCF-7 breast cancer cell line in a dose dependent manner. The
      genistein induced growth inhibition is accompanied by the reduction in the number
      of mitotic cells and overexpression of cyclin dependent kinase inhibitor p21WAF1
      leading to cell cycle arrest. In addition, the telomeric area was significantly
      reduced in genistein treated MCF-7 cells. Analysis of multiple genes involving
      the apoptotic pathway reveals inhibition of Akt activity without affecting the
      steady state levels of Akt protein expression and the down regulation of
      proapoptotic gene BAD expression. From these results, we conclude that genistein
      induced inhibition of cell division is partly mediated by decreased telomere
      length, reduced mitosis and inhibition of Akt activation, leading to induction of
      apoptosis.

PMID- 12792806
TI  - Protein synthesis of eucaryotic cells could be decreased by antisense-DNA of the
      multi KH domain protein vigilin.
AB  - Vigilin, a member of the KH protein family, is exceptional among these proteins
      as it contains 14 KH domains in consecutive order. Vigilin is present in the
      nucleus and the cytoplasm of all eucaryotic cells studied so far and has
      apparently high affinity to tRNA and mRNA. There is circumstantial evidence that
      vigilin expression parallels high translational activity as demonstrated for
      pancreatic cells in vitro and in vivo as well as for carcinoma cell lines. On a
      molecular level we have recently demonstrated that vigilin promotes in vitro the
      export of tRNA from the nucleus to the translational machinery in the cytoplasm
      and may hence function as an intercompartimental conveyor. In the present study
      we show that exposure to a vigilin antisense oligo DNA (VAOD) expectedly resulted
      in a decrease of vigilin-expression, and was concomitant to lower amylase- and
      trypsin synthesis in freshly isolated pancreatic cells. In addition, carcinoma
      cells reacted with an increased mortality under exposure to VAOD giving further
      support for the notion that vigilin participates in cellular life-sustaining
      processes such as protein translation.

PMID- 12792807
TI  - Evolutionary conservation of CCND1-ORAOV1-FGF19-FGF4 locus from zebrafish to
      human.
AB  - The CCND1-ORAOV1-FGF19-FGF4-FGF3-FLJ10261-FADD-PPFIA1-EMS1 locus on human
      chromosome 11q13 is frequently amplified in esophageal cancer, breast cancer, and
      bladder tumors. FGF19, FGF4 and FGF3 genes are implicated in embryogenesis and
      carcinogenesis. We proposed in 2002 the hypothesis that mouse Fgf15 might be the
      ortholog of human FGF19 based on comparative genomics. Here, we identified
      zebrafish fgf19 and oraov1 genes by using bioinformatics to demonstrate the
      hypothesis. Zebrafish fgf19 gene, consisting of three exons, was located around
      nucleotide position 121802-124963 of zebrafish genome draft sequence AL929586.12
      in the reverse orientation. Zebrafish fgf19 (209 aa) was more homologous to
      chicken fgf19 and human FGF19 than to rodent Fgf15. Zebrafish oraov1 gene,
      consisting of five exons, was located around nucleotide position 112172-115838 of
      AL929586.12 in the reverse orientation. Zebrafish oraov1 protein (141 aa) was
      more homologous to human ORAOV1 than to rodent Oraov1. The CCND1-ORAOV1-FGF19
      FGF4 locus was well conserved between human and zebrafish genomes in the order of
      genes, in the direction of genes, and in the exon-intron structure. Rat Ccnd1
      Oraov1-Fgf15-Fgf4 locus was synthenic to mouse Ccnd1-Oraov1 (also known as
      2210010N10Rik)-Fgf15-Fgf4 locus. Fgf15, homologous to human FGF19 and zebrafish
      fgf19, was located on the synthenic locus of human FGF19 and zebrafish fgf19
      within rodent genomes. Based on the evolutionary conservation of the CCND1-ORAOV1
      FGF19-FGF4 locus from zebrafish to human, it was concluded that Fgf15 gene is the
      rodent ortholog of human FGF19 gene.

PMID- 12792808
TI  - Inhibitory effect of pyridoxal 5'-phosphate on endothelial cell proliferation,
      replicative DNA polymerase and DNA topoisomerase.
AB  - Recently, the anti-angiogenic effect of pyridoxal 5'-phosphate (PLP) and
      pyridoxal (PL) was demonstrated in an ex vivo serum-free matrix culture model
      using rat aortic ring. To clarify how vitamin B6 inhibits angiogenesis, this
      study was performed to examine the effect on human umbilical vein endothelial
      cell (HUVEC) proliferation and HUVEC tube formation. Consistent with the result
      on an ex vivo angiogenesis assay, PLP and PL at 250 microM markedly suppressed
      the proliferation of HUVEC, while pyridoxine (PN) and pyridoxamine (PM) were
      inactive at this concentration. Suppression in HUVEC proliferation by PLP and PL
      was evident in a dose-dependent manner within the range of 50-250 microM.
      However, the HUVEC tube formation was unaffected by PLP and PL. The activities of
      replicative DNA polymerase and DNA topoisomerases I and II were also inhibited by
      PLP. These results suggest that vitamin B6 suppresses endothelial cell
      proliferation and angiogenesis at least in part by inhibiting DNA polymerase and
      DNA topoisomerases.

PMID- 12792809
TI  - gamma-Secretase can cleave amyloid precursor protein fragments independent of
      alpha- and beta-secretase pre-cutting.
AB  - Abeta is the major component of amyloid in the brain in Alzheimer's disease and
      is derived from an amyloid precursor protein (APP) by the sequential proteolytic
      processing of two putative proteases, called beta- and gamma-secretase. To
      clarify the mechanism of gamma-secretase processing, we created constructs
      contained the C-terminal domain of APP and analyzed the processing in COS-1
      cells. We found that C-terminal fragments (CTFs) containing a short extra N
      terminal region before the beta-secretase cleavage site were directly processed
      at gamma-secretase cleavage site. This suggests that gamma-secretase cleavage
      occurs independently and is not dependent on alpha- and beta-secretase cleavage.

PMID- 12792810
TI  - Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes
      chemosensitivity through decreased pRB and increased E2F-1 expressions.
AB  - Human gastric cancer SNU 484 cells express mutant p16, which migrates slower than
      the wild-type p16. We constructed an expression vector containing human p16 cDNA
      to evaluate the cytotoxic effects of exogenous p16 expression on SNU 484 cell
      proliferation and to explore the potential use of p16 in cancer gene therapy. The
      stable transfectant expressing wild-type p16, showed a 2-fold slower growth rate
      than mock and non-infected cells through down-regulation of CDK4-dependent kinase
      activity. When cells were transiently transfected with mock or p16 encoded
      vector, the mock cells showed larger survival colonies than those of wild-type
      p16. Furthermore, p16-expressing stable transfectant was readily progressed into
      cell death by combination with treatment of chemotherapeutic drug in a dose
      dependent manner. According to western blot analysis, both decreased expression
      of pRB and increased expression of E2F-1 may contribute to the susceptibility of
      cell death. Our data indicate that exogenous wild-type p16 induces delayed cell
      proliferation and promotes chemo-sensitivity in the gastric cancer cell line,
      implying the promise of p16 in cancer gene therapy.

PMID- 12792811
TI  - Mobile telephones and cancer: is there really no evidence of an association?
      (review).
AB  - Two Swedish epidemiological studies have shown an association between the use of
      mobile telephones, mainly of the analogue type, and brain tumours. These findings
      have been corroborated in a Finnish study. Supportive evidence has also come from
      studies in USA, but these investigations, as well as a Danish study, are
      inconclusive due to e.g., few exposed subjects, short latency periods and
      methodological shortcomings. The Swedish Radiation Protection Authority (SSI)
      engaged two epidemiologists from a private company to conduct a review of the
      literature. They claimed that use of mobile telephones is not associated with
      increased risk for brain tumours. Their conclusion was, however, based on an
      unbalanced view of current literature in favour of studies showing no
      association. These circumstances are further explored in this communication.

PMID- 12792812
TI  - Effects of HDL3 on the expression of matrix-degrading proteases in human
      endothelial cells.
AB  - Modified lipoproteins have been suggested to modulate the expression of matrix
      degrading proteases in the vascular wall. Since oxidized high density lipoprotein
      (HDL) has been found in atheromatous plaques and receptors for modified HDL are
      present on endothelial cells, we investigated the role of native and oxidized
      HDL3 on the expression of 35 proteases and their inhibitors in human endothelial
      cells using microarray analysis. Matrix metalloproteinase (MMP)-1, -2, -10, -13
      and -14, tissue inhibitor of MMP (TIMP)-1, -2 and -3, cathepsin B and D, and
      cystatin C were expressed under basal conditions, of which MMP-10 and cystatin C
      expression have not been described before in endothelial cells. Native HDL3
      increased MMP-1 and MMP-14 expression and decreased MMP-13 expression, whereas
      oxidized HDL3 increased PAI-1 and MMP-1 expression. The expression pattern was
      confirmed by quantitative real-time PCR. In summary, a large repertoire of matrix
      degrading proteases is expressed in endothelial cells, an expression that can be
      modulated by native and oxidized HDL3.

PMID- 12792813
TI  - Confirmation of CLIM2/LMX1B interaction by yeast two-hybrid screening and
      analysis of its involvement in nail-patella syndrome.
AB  - Nail-patella syndrome (NPS), an autosomal dominant disorder characterized by nail
      dysplasia, absent or hypoplastic patellae, iliac horns, and often associated with
      nephropathy and, less frequently, with open angle glaucoma, is caused by
      mutations in the LMX1B gene. Inter-familial and intra-familial phenotypic
      variability raises the question whether modifier genes can be identified to
      explain differences in the expression and severity of clinical features of NPS.
      Genes encoding proteins that interact with the LMX1B protein are good candidates
      and, therefore, methods to search for interactions can be used to this purpose.
      By the yeast two-hybrid screening we detected the CLIM2 gene as a LMX1B
      interactor, confirming previous reports which described the same interaction by
      biochemical methods. Sequencing of the CLIM2 coding region in seven NPS cases in
      which no LMX1B mutation had been found, did not detect any molecular variant in
      these patients. Moreover, by genotyping a polymorphic dinucleotide repeat close
      to the CLIM2 gene in affected members of a large Dutch NPS family with high
      incidence of nephropathy, we were unable to find a correlation between the
      presence of a specific allele and the expression of nephropathy. In conclusion,
      although the results of this study could not provide any proof of CLIM2
      involvement in the pathogenesis of NPS or in determination of the clinical
      phenotype, we suggest that the CLIM2 gene can be considered as a good candidate
      for further studies on normal and disturbed kidney development associated with
      NPS or other hereditary glomerulopathies.

PMID- 12792814
TI  - Prostaglandin E2 synthesis in human monocyte-derived dendritic cells.
AB  - Prostaglandin E2 (PGE2), which is generated by the enzymatic activity of
      cyclooxygenase-1 and -2 (COX-1/2), plays a central role in the maturation process
      of dendritic cells (DC). Since regulation of COX-1/2 expression in human DC is
      only partially understood, we addressed the expression and activity of COX-1/2 in
      these cells. Here we show that lipopolysaccharide (lps) induces COX-2 mRNA and
      protein synthesis as well as the release of PGE2 in human interleukin-4 and
      granulocyte/macrophage colony-stimulating factor-differentiated monocyte-derived
      DC cultivated in the presence of 1% human plasma. Moreover, we found that lps
      induces p38 stress-activated protein kinase (p38) in these cells and inhibitors
      of p38 blocked lps-induced COX-2 expression and activity. Our data indicate that
      during lps-induced maturation p38 regulates COX-2 expression and PGE2 synthesis
      in DC.

PMID- 12792815
TI  - Cloning and structural characterization of the human histone deacetylase 6 gene.
AB  - Histone deacetylases (HDACs) play a central role in the modification of chromatin
      structure and thus in the regulation of transcription and cellular
      differentiation. Based on structural and functional similarities, mammalian
      histone deacetylases may be grouped into three categories, class I HDACs, which
      are homologs of the yeast histone deacetylase RPD3, class II HDACs, which share a
      significant degree of homology with the yeast histone deacetylase HDA1 and class
      III HDACs which are closely related to the yeast SIR2 protein. We have isolated
      and characterized the human HDAC6 genomic sequence, which spans a region of
      21,923 bp and which has one single genomic locus. Determination of the exon
      intron splice junctions established that HDAC6 is encoded by 28 exons ranging in
      size from 41 bp (exon 5) to 677 bp (exon 24). Characterization of the 5' flanking
      genomic region, which precedes the HDAC6 open reading frame, revealed a TATA- and
      CCAAT-boxless promoter that contains a 1 kb CpG island. The 3,648 bp human HDAC6
      mRNA encodes a 1,215 aa protein with a predictive molecular weight of 131.4 kDa.
      Fluorescence in situ hybridization analysis localized the human HDAC6 gene to the
      subband border of chromosome Xp11.22-23, a region which is characterized by
      frequent gains and losses of chromosomal material in several types of cancer and
      neurological disorders.

PMID- 12792817
TI  - Are molecular features of a chromophobic cell renal cell carcinoma correlated
      with clinical findings?
AB  - Lipids extracted from three human renal neoplasms have been characterized by
      means of 13C magnetic resonance spectroscopy. The presence of free cholesterol,
      high levels of unsatured fatty acids, and phosphatidylcholine, and a very high
      fatty acids/cholesterol ratio makes the lipid profile of a rare chromophobe cell
      carcinoma very similar to that of an oncocytoma. On the contrary, clear cell
      carcinomas are mainly characterized by the presence of almost fully esterified
      cholesterol and by a markedly lower level of unsatured fatty acids. Since
      chromophobic cell carcinomas have a more favourable prognosis than clear cell
      carcinomas, their analogy in the lipid composition with a benign renal neoplasm
      could have a clinical significance. In particular, our report suggests that
      cholesteryl esters and high levels of unsatured fatty acids could be a marker of
      a poor (clear cell carcinomas) or a good (chromophobic cell carcinomas)
      prognosis, respectively. More in depth studies are required of the molecular
      composition of the neoplastic pathologies that add new knowledge, with potential
      clinical implications.

PMID- 12792818
TI  - Endometriotic patient serum enhances endometrial stromal cell proliferation and
      viability: a preliminary study.
AB  - Decreased numbers of eutopic endometrial apoptotic cells have been reported in
      endometriotic patients, indicating the possibility of antiapoptotic effects of
      their sera. In this preliminary study, we examined the effects of serum from 8
      endometriotic patients on cell proliferation and viability of eutopic human
      endometrial stromal cells obtained from 3 non-endometriotic women. Endometrial
      stromal cell proliferation was stimulated in a dose-dependent manner by all sera
      examined, including those of healthy women. Compared with the sera from healthy
      women, all sera from 8 endometriotic patients significantly enhanced stromal cell
      proliferation, and 5 of the 8 sera significantly inhibited 8-Br-cAMP-activation
      induced cell death in endometrial stromal cells. Considering these results, we
      suggest that the stromal cell growth and surviving factor(s) from the serum of
      most endometriotic patients have a higher activity, which may stimulate ectopic
      implantation and proliferation of endometrial stromal cells.

PMID- 12792816
TI  - Leptin inhibits decidualization and enhances cell viability of normal human
      endometrial stromal cells.
AB  - Recent reports have demonstrated that the peritoneal fluid and serum
      concentrations of leptin are increased in women with endometriosis. However, the
      pathophysiological roles of leptin in endometriosis have not been well
      characterized. In this study, we examined the direct effects of leptin on normal
      human endometrial stromal cells using an in vitro decidualization assay system
      with 8-Br-cAMP, a decidualization inducer. No effects of leptin on cell viability
      and prolactin secretion were found in unstimulated endometrial stromal cells.
      Leptin dose-dependently enhanced the viability of stromal cells co-stimulated
      with 8-Br-cAMP and leptin while PRL secretion from the cells was significantly
      inhibited in a dose-dependent manner. As for 8-Br-cAMP-stimulated cells, leptin
      significantly enhanced their cell viability in a dose-dependent manner but not
      their PRL secretion. These results indicate that leptin enhances the cell
      viability of PRL-non-secreting 8-Br-cAMP-stimulated stromal cells, and that it
      inhibits the decidualization process of endometrial stromal cells. Increased
      leptin in endometriotic patients might play an antiapoptotic role in some
      activated ESCs in the peritoneal cavity to stimulate endometrial cell
      implantation, and might cause infertility by inhibiting stromal decidualization.

PMID- 12792819
TI  - Low-dose bleomycin induces targeted gene repair frequency in cultured melan-c
      cells using chimeric RNA/DNA oligonucleotide transfection.
AB  - We attempted to raise the frequency of targeted gene repair attained by RNA/DNA
      chimeraplasty through activation of endogenous DNA recombination/repair system in
      cultured melan-c cells. For elevating the repair activity, either gamma-ray
      irradiation at 2 Gy or bleomycin addition at 5 nM to the culture medium was done.
      Subsequently, the tyrosinase-targeted chimeric RNA/DNA oligonucleotides were
      transfected. The frequency of targeted gene repair was assessed by three means,
      i.e., changes in cell color from transparent to dark black, restriction fragment
      band patterns, and DNA sequencing analysis. The results indicated that the gamma
      ray irradiation did not improve the efficiency at all. In contrast, the low-dose
      bleomycin addition induced the frequency of targeted base conversion, compared
      with transfection with chimeric RDOs alone, although the frequency was still
      insufficient and varied from 0.1 to 10% of the total cultured cells.

PMID- 12792820
TI  - Effects of preproglucagon-derived peptides and exendins on steroid-hormone
      secretion from dispersed adrenocortical cells of normal and streptozotocin
      induced diabetic rats.
AB  - Many lines of evidence have shown that preproglucagon-derived peptides affect
      steroid secretion from dispersed adrenocortical cells, and that streptozotocin
      (STZ)-induced experimental diabetes alters adrenocortical-cell function. Hence,
      we compared the effects of glucagon, glucagon-like peptide (GLP)-1 and GLP-2 on
      basal and ACTH-stimulated secretion of dispersed adrenocortical cells from normal
      and STZ-induced diabetic rats. We also examined the effects of exendins (EX) 3
      and 4, because EX4 is known to be a potent and long-lasting agonist of GLP-1
      receptors. STZ-induced diabetes moderately enhances basal and ACTH-stimulated
      secretion from dispersed zona glomerulosa (ZG) cells, without significantly
      affecting corticosterone production from dispersed zona fasciculata-reticularis
      (ZF/R) cells. In normoglycemic rats, glucagon increased basal aldosterone and
      corticosterone secretion from ZG and ZF/R cells, GLP-2 raised both basal and ACTH
      stimulated aldosterone secretion and ACTH-stimulated corticosterone output, and
      EX4 increased basal corticosterone secretion. In contrast, glucagon, GLP-2 and
      EX4 did not elicit secretory responses from adrenocortical cells of diabetic
      rats. GLP-1 and EX3 did not alter secretion of dispersed adrenocortical cells of
      either normal or STZ-treated rats. Taken together, our findings indicate that
      preproglucagon-derived peptides enhance steroid secretion from adrenocortical
      cells of normal, but not STZ-induced diabetic rats. It is suggested that the
      prolonged exposure to low concentrations of insulin causes unresponsiveness of
      adrenocortical cells to glucagon, GLP-2 and EX4, which may contribute to the
      hyporeninemic hypoaldosteronism and alterations in glucocorticoid metabolism
      occurring in experimental diabetes.

PMID- 12792821
TI  - The free radical scavenger edaravone suppresses experimental closed duodenal loop
      induced acute pancreatitis in rats.
AB  - Recent studies suggest that the enhanced release of reactive oxygen species (ROS)
      plays an important role in the pathogenesis of clinical acute pancreatitis. In
      the present study, we investigated the effects of the free radical scavenger
      edaravone, which is used clinically as an anti-stroke agent, in the development
      of experimental closed duodenal loop (CDL)-induced acute pancreatitis. In the CDL
      pancreatitis model, after edaravone and vehicle saline were injected
      intravenously, pancreatitis was induced for 7 h by the CDL technique. The
      subsequent ascites volume, wet pancreatic weight, serum amylase levels, and
      pancreatic tissue lipid peroxide levels were evaluated. Pancreatic tissue damage
      was also evaluated histologically. In this CDL-induced pancreatitis model,
      edaravone treatment tended to reduce the ascites volume and inhibit the increases
      in the wet pancreatic weight. Edaravone also tended to reduced the microscopic
      mucosal damage scores and pancreatic tissue lipid peroxide levels. In particular,
      the serum amylase levels in the edaravone-treated rats (1-20 mg/kg i.v.) were
      significantly reduced as compared to the vehicle-treated rats. These results
      strongly support the involvement of ROS in the pathogenesis of CDL-induced acute
      pancreatitis and cytoprotective effects of free radical scavender against
      pancreatic acinar cells. A clinical effect for edaravone against acute
      pancreatitis is strongly expected.

PMID- 12792822
TI  - The free radical scavenger edaravone suppresses experimental dextran sulfate
      sodium-induced colitis in rats.
AB  - Recent studies suggest that the enhanced release of reactive oxygen species (ROS)
      plays an important role in the pathogenesis of clinical inflammatory bowel
      diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present
      study, we investigated the effects of the free radical scavenger edaravone, which
      is used clinically as an anti-stroke agent, in the development of experimental
      dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w
      of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline
      were injected subcutaneously twice a day. After the experimental period, the wet
      colonic weight, macroscopic mucosal damaged area, histological damage score,
      mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum
      interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model,
      edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic
      weight, macroscopic damaged area, and the histological damage score. Edaravone
      treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate
      level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day
      significantly reduced mucosal MPO activity and serum IL-6 level. These results
      strongly support the involvement of ROS in the pathogenesis of DSS-induced
      colitis. A clinical effect for edaravone against IBD patients is strongly
      expected.

PMID- 12792823
TI  - ErbB2 and the antimetastatic nm23/NDP kinase in regulating serum induced breast
      cancer invasion.
AB  - The erbB2 gene is often found amplified and/or overexpressed in breast cancer in
      which it has clinical relevance as prognostic and predictive factor. It is
      involved in growth regulation and has a role in the initial phases of cell
      proliferation, while in vivo and in vitro studies have suggested an involvement
      also in cell invasion and metastases. It is not clear if these two roles are
      mutually exclusive and little is known about the mechanisms by which erbB2 may be
      involved in the control of these processes. Our previous data on patient series
      suggested that erbB2 might be regulated in different ways depending on the
      neoplastic status of the cells and that it might be involved in different
      regulatory pathways. To test this hypothesis we have measured the serum-dependent
      regulation of erbB2 as a function of the expression of the antimetastatic gene,
      nm23, in a panel of breast cancer cell lines. The experimental model consisted of
      three cell lines having different proliferative and invasive potentials: a non
      metastatic estrogen receptor (ER) positive cell line, MCF-7; a highly metastatic
      ER negative cell line, MDA-MB435; and the MDA-MB435 cell line transfected with
      the nm23-H1 antimetastatic gene (clone H1-177) which has lost the ability to
      invade and metastasize. We first analysed the serum concentration dependence of
      invasion and proliferation after 3-4 days of serum deprivation confirming the
      proliferative and invasive potential of the three cell lines. Modulation of erbB2
      expression by different concentrations of serum was then studied. ErbB2
      expression in MCF-7 cells showed a complex pattern due to serum modulation,
      whereas, it was not longer regulated by serum in the MDA-MB435 cell line. In H1
      177 cells the erbB2 response to serum was restored and it was very similar to
      that observed in MCF-7. These data showed a tight association between nm23 and
      the regulation of erbB2 expression by serum factors suggesting that the role of
      erbB2 in invasion might be dependent on nm23 expression.

PMID- 12792827
TI  - [Development of grade level norms for reading speed and writing errors of Turkish
      elementary school children].
AB  - INTRODUCTION: Despite being in the normal intelligence range, children with
      learning disorders fail to reach expected academic performance levels. Clinical
      diagnosis and decisions for therapeutic management for these children require the
      use of academic achievement tests. The lack of reliable achievement tests and age
      appropriate reading speed and writing norms hinder clinical studies with Turkish
      children. OBJECTIVE: To develop and establish Turkish norms of an assessment tool
      which will aid in the objective evaluation and diagnosis of learning disorders.
      METHOD: A total of 2572 children attending the 1st-5th grades of randomly
      selected elementary schools belonging to different socioeconomic levels
      constituted the sample of the study. The number of words read from grade-level
      appropriate scripts in 1 minute indicated reading speed. A three-sentence script
      containing repeating consonants p-b-t-d-m-n-v-f was dictated to determine writing
      errors. RESULTS AND DISCUSSION: Grade levels of reading speed increase and
      writing errors decrease as the child grows. Mean, standard deviation and standard
      error scores indicate that objective academic achievement criteria were reached.
      Achievement differences according to gender and sociocultural status, which were
      not the subject of this study, also seem to be important variables.

PMID- 12792828
TI  - [Neuropsychological functions in early and late onset alcoholism].
AB  - OBJECTIVE: To compare late and early onset alcoholism with regard to
      neurocognitive functions. METHOD: Using the age of alcoholism onset as a
      criterion, 20 late onset and 14 early onset male alcoholics were included in the
      study. Eleven healthy male volunteers with similar demographic features were
      included as a control group. Alcohol and drug modules of Schedules for clinical
      Assessment in Neuropsychiatry (SCAN) were administered to each subject in order
      to gather data on alcohol intake variables. The life time severity of drinking
      problems was assessed by the Michigan Alcoholism Screening Test (MAST). All
      patients met the diagnostic criteria of ICD-10 for alcohol dependence. The
      neuropsychological battery consisted of the Wisconsin Card Sorting Test, the
      Wechsler Memory Scale and Word Fluency Tests. The battery was administered to
      each patient 15 days after their entry into detoxification programme when the
      withdrawal syndrome ceased and all the psychotropic medications stopped for at
      least 1 week. RESULTS: Compared with the control group, both groups of alcoholic
      patients displayed impairment in frontal lobe functions and memory.
      Neuropsychological test performance did not differ between early and late onset
      groups. CONCLUSIONS: The results of this study suggest that subtypes of
      alcoholism based on a one-dimensional clinical application of Cloninger's
      typology are not associated with discriminatively different patterns of
      neuropsychological abnormalities.

PMID- 12792829
TI  - [Dysthymic disorder in primary health care].
AB  - OBJECTIVE: The aim of this study was to investigate the epidemiological and
      clinical characteristics of dysthymic disorder of the primary health care level.
      METHOD: Parts of the Composite International Diagnostic Interview (i.e. sections
      on demographic variables and depressive and dysthymic disorders) the General
      Health Assessment Form, the Brief Disability Questionnaire, and a Patient
      Assessment Form were applied to 1997 consecutive patients seen by primary care
      physicians in 10 cities. RESULTS: The frequency of dysthymic disorder according
      to DSM-IV criteria in the primary care patients studied was 3.5%. "Fatigue or
      loss of energy", "diminished ability to think or concentrate", "indecisiveness",
      "insomnia" and "hopelessness" were the most frequent symptoms. 73.9% of patients
      with dysthymic disorder also had a chronic disorder and 78.3% of patients with
      dysthymic disorder met the criteria for major depressive disorder. 71.4% of
      patients with dysthymic disorder presented only somatic complaints to general
      practitioners. Disability ratios were higher in patients with dysthymic disorder
      than in patients without. General practitioners recognised depression in only
      13.8% of patients with dysthymic disorder. CONCLUSION: General practitioners can
      not recognise dysthymic disorder in primary health care patients. This result
      emphasises the need for research on the failure to recognise dysthymic disorder
      in primary health care patients.

PMID- 12792830
TI  - [Cognitive and emotional factors in major depression and suicide].
AB  - OBJECTIVE: Suicide is defined as ending ones life with his own will. It is the
      most frequent reason of death in psychiatry and accepted as tragic since it can
      be the cause of young peoples deaths. In this study patients with recent suicide
      attempt were compared with major depression patients without suicide history and
      the control group by means of emotional and cognitive variables since suicide is
      an important complication of major depression and both have similar cognitive
      processes. METHOD: Thirty patients from each group were assessed by means of
      demographic variables, Beck depression inventory, UCLA loneliness scale,
      automatic thoughts scale, and suicide probability scale. Results were analyzed by
      SPSS for Windows. RESULTS: Three groups were not statistically different by means
      of demographic variables except age and sex. Women were high risk group for major
      depression and suicide. The mean age of suicide group was significantly lower
      than major depression group. When analyzed by means of emotional and cognitive
      variables; the suicide group had high depressive symptomatology. Automatic
      thoughts scale scores were higher in the suicide group than the major depression
      group. Three groups did not differ by means of UCLA loneliness scores. When
      groups were compared by suicide probability scale; the major depression group and
      the suicide group did not differ in sub scales except hostility. CONCLUSION:
      Major depression groups high scores in hostility scale which may be the
      explanation of suicide; is one of the most important findings in this study

PMID- 12792831
TI  - [Social skills training in psychosocial therapy of schizophrenia: a multicenter
      study for symptom management and medication management modules].
AB  - OBJECTIVE: It is known that psychosocial skills training programs increase the
      efficacy of schizophrenia treatment. The aim of this study was to carry out the
      Turkish version of two modules of a commonly used program, Social Skills Training
      (Medication Management and Symptom Management Modules), and to determine its
      possible benefits. METHOD: The study was carried out at three sites. Fifty
      schizophrenic patients who were at least literate and who did not have language
      problems or organic mental diseases, aged 18-60, using antipsychotic agents in a
      standard dose and in a stable phase were included in the study. Eight training
      groups were formed. Each group consisted of 5-7 individuals and the study took
      approximately eight months. The Brief Psychiatric Rating Scale, the Quality of
      Life Scale: an instrument for rating the schizophrenic deficit syndrome, the Drug
      Treatment Compliance Scale and Pre- and Post-Tests of Social Skills Training were
      applied to the patients before and after the group education The scores of the
      rating scales were compared. RESULTS: Thirty-eight (76%) patients completed the
      study. The mean age of the patients was 32 +/- 7, 84% were men, 58% had received
      less than 11 years, of education 84% had never married, and 97% were living with
      their families. The mean age of illness onset was 20 +/- 5 years, and the mean
      duration of the illness was 12 +/- 7 years. At the end of the study, the Brief
      Psychiatric Rating Scale scores (baseline 42.0, after the training 37.1, p<0.02),
      and the Quality of Life Scale scores (baseline 67.5, after the training 75.3,
      p<0.01) were significantly changed. The level of knowledge of the patients about
      the medication and symptoms of schizophrenia increased 20.6%. Drug treatment
      compliance had also increased by the end of the study. CONCLUSION: The results
      show that this program contributed to the treatment compliance and treatment
      efficacy in schizophrenia. Increased treatment efficacy might have played a role
      in increasing of the quality of life a long with the group milieu. It may be
      concluded that this social skills training program, which did not encounter any
      problems in application, may contribute significantly to the treatment of
      schizophrenia.

PMID- 12792832
TI  - [Predicting factors of eating disorders and general psychological symptoms in
      female college students].
AB  - OBJECTIVE: To compare and determine the relative effects of six of the variables
      (family functioning, self-esteem, obsessive-compulsive symptoms, depressive
      symptoms, locus of control and Body Mass Index-BMI) related to the etiology of
      eating disorders in predicting eating disorder symptoms and the general symptom
      index. METHOD: Two hundred and ninety-two female college students completed the
      Rosenberg Self-Esteem Scale (RSES), the Family Assessment Device (FAD), the
      Eating Attitude Test (EAT), the Symptom Check List (SCL-90-R), Rotter's Internal
      External Locus of Control Scale (RIELCS), and the Beck Depression Inventory
      (BDI). Multiple regression analysis was employed, and scores of the obsessive
      compulsive subscale of SCL-90-R, BMI, RSES, FAD, BDI and RIELCS were used as
      predictors of EAT total scores. The second multiple regression analysis was
      employed with the same independent variables as predictors of the General Symptom
      Index (GSI) of SCL-90-R. RESULTS: Obsessive-compulsive symptoms were the best
      predictor of the total score of EAT, and the second was the BMI scores.
      Depressive symptoms and self-esteem scores were significantly correlated with EAT
      scores but these variables were not chosen for inclusion in the regression
      equation. There was a strong relation between scores on BMI and scores on EAT.
      BMI scores were correlated nonsignificantly with the scores of the other
      variables. RIELCS and FAD scores were not significantly correlated with EAT
      scores. Obsessive-compulsive symptoms were also the best predictor of GSI of SCL
      90-R and the second best predictor was the RSES. FAD was significantly correlated
      with SCL-90-R GSI scores, depression and obsessive compulsive scores. CONCLUSION:
      It appears that obsessive-compulsive symptoms were the best predictor of
      pathologic eating behavior. BMI was the second predictor of EAT scores. Locus of
      control and family functioning were not correlated with eating pathology. Family
      functioning scores were significantly correlated with the GSI scores, and
      depressive and obsessive-compulsive symptoms. Obsessive-compulsive symptoms were
      also the best predictor of the GSI scores.

PMID- 12792833
TI  - [The concept of placebo and the effect of placebo].
AB  - The discussions about what placebo means and how its effect occurs go far back in
      the history of medicine. In general medicinal understanding, placebo means the
      subjective feeling of a positive effect in response to something that is used for
      curative intentions. In spite of difficulties in its definition and unknown
      content, its existence is generally accepted. What is discussed is its level of
      effectiveness in any disorder and medication. The placebo effect varies not only
      among diseases but also among regions and countries. Even the physicians' belief
      in a placebo increases its effect. Another interesting point about the placebo is
      its side effects. In many placebo controlled studies, the side effects of the
      placebo are found to be greater than those of real drugs. Different from other
      diseases, psychiatric disorders have strong connections with the placebo effect.
      The results of many studies support this idea. The increasing importance of
      placebos in psychiatry is really an interesting subject. For some people, the
      reason for this is hidden in the nature of psychiatric diseases. However,
      nonpharmacologic placebos such as "inspiration", "convincing", "confidence", and
      "belief" are believed to play a central role in psychiatry. In this article,
      placebo (the placebo effect) is defined, the implications of placebo in general
      medicine or psychiatry are discussed, and specific or nonspecific treatment
      methods are explained. The effects of a placebo on both the patient and the
      physician are emphasized. The significance of the placebo effect in psychiatry is
      also mentioned; and a new point of view, based upon the importance of
      symbolization and satisfaction is introduced in treatment and related action
      mechanisms.

PMID- 12792834
TI  - [A review on augmentation of clozapine treatment].
AB  - Clozapine is one of the most effective pharmacological agents in the treatment of
      treatment-resistant patients with schizophrenia, schizoaffective and bipolar
      disorder. Nevertheless, there is still an important proportion of patients who do
      not respond to clozapine treatment given at a sufficient dose and duration. Some
      patients cannot tolerate the dosage necessary for an adequate treatment. Case
      reports, series, various open and controlled trials suggest that there are
      effective strategies of augmenting clozapine treatment in such cases. In this
      article, strategies of clozapine augmentation are reviewed in the light of
      findings related with the efficacy, safety and pharmacokinetic/dynamic
      interaction profiles of such combinations used for augmentation. To our
      knowledge, there is only one study in the current literature reviewing this
      subject. Augmenting strategies are reviewed through the combination of clozapine
      with the serotonin reuptake inhibitors (SSRI), typical and atypical
      antipsychotics, mood stabilizers, NMDA agonists and electroconvulsive treatment
      (ECT).

PMID- 12792836
TI  - [Hunting the susceptibility gene for psychosis: a study of a family overloaded
      with schizophrenia and bipolar disorder].
AB  - OBJECTIVE: It is a long-standing debate whether schizophrenia and bipolar
      disorder are separate clinical entities or different poles on a spectrum. In this
      paper we present a family overloaded with schizophrenia, and schizoaffective,
      bipolar and unipolar disorders. Common loci for bipolar affective disorder and
      schizophrenia were tested by linkage analysis. METHOD: The pedigree of an index
      family which had been followed by our department for nearly 20 years was
      extended. The index family members were diagnosed by two psychiatrists with two
      distinct structured interview schedules (SCID-I and SADS-L). A field visit was
      undertaken for the evaluation of the extended family (n= 40) and SADS-L was used
      for psychiatric assessment. Blood samples were collected for molecular studies. A
      linkage study has been performed for overlapping susceptibility regions for
      schizophrenia and affective disorders (10p13-p12, 13q32, 18p and 22q11-q13) and a
      locus (20p11.2-q13) to which a linkage had been shown in a bipolar family who
      lived in the same region. Both autosomal recessive and dominant mode of
      inheritance were assumed in the analysis. RESULTS: The pedigree consisted of 108
      individuals of whom 23 are affected. All affected subjects presented psychotic
      features except for 5 unipolar patients. The pedigree was reconstructed with
      respect to psychosis phenotype. Further linkage and haplotype analysis excluded
      all five loci on chromosomes 10, 13, 18, 20 and 22 under both autosomal dominant
      and recessive modes of inheritance assumption. CONCLUSION: A potential linkage
      between the psychosis gene and reported susceptibility loci overlapping in
      bipolar affective disorder and schizophrenia was not demonstrated Genome-wide
      analysis should be performed.

PMID- 12792837
TI  - [Phenomenological differences between adolescent and adult onset mania: a
      comparative study].
AB  - OBJECTIVE: The aim of this study is to determine the relationship between age of
      onset and phenomenology of bipolar affective disorder (mania). METHOD: The
      current and retrospective diagnoses of the patients were made according to DSM-IV
      Bipolar Affective Disorder (mania) criteria. Sociodemographic features, clinical
      features, type of episode, number and length of hospitalizations were
      investigated in three groups which were consisted of adolescent-onset adolescents
      (n=60), adolescent-onset adults (n=60) and adult-onset adults (n=60). The groups
      were determined according to age of onset and current age categories. All
      patients have been assessed by Structured Clinical Interview for DSM-IV-Clinical
      Version (SCID-I), Young Mania Rating Scale (YMRS), Hamilton Depression Rating
      Scale (HAM-D) and Scale for the Assessment of Positive Symptoms (SAPS). RESULTS:
      The groups were consisted of equal numbers of women and men. Rate of single
      (%51.7) and divorced patients (%21.7), rate of unemployment status (%70) were
      higher in adolescent-onset patients than adult-onsets. Adolescent-onset
      adolescents and adolescent-onset adults were different from adult-onset patients
      with respect to mixt episodes (%26.7, %15) and mood congruent or incongruent
      psychotic features (%35/%50, %31.7/%66.7) and length of hospitalization (23.9+/
      4.8, 23.8+/-3.9). CONCLUSION: Adolescent-onset of illness causes higher
      probability of mixt episodes, psychotic features such as mood congruent or
      incongruent hallucinations and delusions. This study supports the hypothesis that
      adolescent-onset mania may be a different subtype than adult-onset mania with
      respect to type of episode, phenomenology, and clinical features.

PMID- 12792838
TI  - [Reliability and validity of Turkish version of magical ideation scale in
      university students].
AB  - OBJECTIVE: Schizoptypal disorder shares many clinical, neuropsychological and
      neurophysiological features with schizophrenia and is included in the
      schizophrenia spectrum. Patients with schizotypal disorder or individuals with
      mild schizotypal features are therefore highly valuable in the study of
      neuropsychological and neurophysiological characteristics of psychosis, and in
      particular schizophrenia, as they are likely to be free of the potential
      confounding factors of medication, chronic hospitalization and manifest
      psychosis. We report here the psychometric properties of the Turkish version of
      the Magical Ideation Scale (MIS), a self-report questionnaire that focuses on
      delusion-like beliefs and hallucination-like experiences and that has been used
      to quantify an important dimension of schizotypy. METHOD: Internal consistency
      and high cut-off scores were studied in 332 medical students. Forty-three
      students were readministered the scale 3 weeks later, and 96 received the
      Paranormal Belief Scale-R (PBS-R) along with the MIS, in order to measure test
      retest reliability and convergent validity, respectively. RESULTS: The internal
      consistency of the scale is satisfactory with a Cronbach alpha coefficient of
      0.78. Test-retest scores are highly correlated (r= 0.84). The high cut-off score
      is 21 for males, 23 for females, and 22 for the whole sample. Convergent validity
      was established by the significant correlation between the total MIS and PBS-R
      scores (r= 0.61). CONCLUSIONS: The scale is valid and reliable for studies that
      require a standard quantification of schizotypal signs and symptoms in young
      university students.

PMID- 12792839
TI  - [Nicotine dependence and psychiatric comorbidity among university students].
AB  - OBJECTIVE: The relationship between psychiatric disorders and nicotine use has
      been studied in recent years. In this study, the comorbidity between psychiatric
      disorders and nicotine dependence (ND) and nicotine abstinence (NA) was evaluated
      in a randomly selected group of university students. METHOD: We used the 12-month
      version of CIDI 2.1 (Composite International Diagnostic Interview) for the
      interviews of a total of 323 students (M/F: 168/155), who were randomly selected
      among and represented all students in Selcuk University. The mean age of students
      was 20.9 (SD: 5.4, range: 16-34). ND, NA and other psychiatric disorders were
      diagnosed according to DSM-IV criteria. RESULTS: One-year prevalence of ND and NA
      was 17% (n=55) and 4% (n=13), respectively among the 323 students interviewed.
      The prevalence of any psychiatric disorders other than ND and NA was 26.3%
      (n=85). Students who had psychiatric disorders had a higher relative risk than
      those who did not have psychiatric disorders (30.6% versus 12.2%, odds ratio:
      3.2, 95% CI 1.7-5.8; p<0.001). ND was also observed more commonly in students who
      were diagnosed with any of these disorders than in those free of these disorders:
      alcohol dependence or abuse (72.7% versus 15.1%), any mood disorder (36.0% versus
      15.4%) and any anxiety disorder (29.3% versus 13.9%). CONCLUSION: This study
      suggests that ND in young adults is associated with a higher rate of psychiatric
      disorders.

PMID- 12792841
TI  - [Biological trait markers of alcohol dependence].
AB  - OBJECTIVE: The early detection of individuals at high risk for the future
      development of alcohol dependence and the identification of trait markers for
      alcoholism may be useful for taking necessary measures to protect the individuals
      from alcoholism, for enlightening the aetiology of the illness, and even for the
      development of the new treatment methods. This paper reviews in detail the
      results of studies of trait markers in alcoholism, which have intensified
      particularly in recent years. Some data of the investigations indicate that a
      trait marker for alcoholism or a subgroup of alcohol-dependent patients may be
      developed: with abnormal adenylyl cyclase (AC) activity, reduced monoamine
      oxidase (MAO) levels, hypothalamo-pituitary-adrenal (HPA) axis abnormalities, b
      endorphin abnormalities, reduced amplitude of P300 event-related potential, D2
      receptor down-regulation, and decreased sensitivity to alcohol challenge as risk
      factors; and abnormal aldehyde dehydrogenase isoenzyme patterns as a protective
      factor. The review concludes that although a comprehensive trait marker for
      alcoholism has not yet been identified, one can hope for the identification of
      some consistent biological markers in a subgroup of alcohol dependents over the
      course of time.

PMID- 12792840
TI  - [Sociodemographic and clinical characteristics of patients with conversion
      disorder].
AB  - OBJECTIVE: To determine the sociodemographic, and clinical characteristics, and
      comorbid diagnosis of patients with conversion disorder, and also to evaluate the
      relationship between the duration of conversion and comorbid diagnosis and
      personality factors. METHOD: Seventy-two patients who were diagnosed with
      conversion disorder according to DSM-IV criteria, were included in this study.
      The Hacettepe Personality Inventor, was administered to all patients, and they
      were divided into two groups. The first group had conversion symptoms for four
      years (Group 1), while the other group had conversion symptoms more than four
      years (Group 2). RESULTS: Sixty-three of patients were female, 9 were males. The
      average onset age of the disorder was 25.9+/-7.5. Seventy patients (97,2%) had
      received a maximum of 11 years of education. 40.3% of patients sought treatment
      because of seizures or convulsions, 40,3% because of sensory symptoms or
      deficits, 5% because of motor symptoms or deficits, and 12,6% because of mixed
      presentations. The mean duration of complaints was 4.2+/-1.4 years (min= 1, max=
      20). 59.7% of the patients had prominent stress before the onset of the
      conversion symptoms. There were 12 (28.6%) comorbid psychiatric disorders in
      Group 1, and 17 (56,7%) in Group 2. Although the mean neurotic trend scores in
      Group 2 (6.1+/-4.1) were higher than Group 1 (3.1+/-3) (p=.03). The mean
      emotional resolution scores were lower in Group 2 (4.2+/-3.5) than in Group 1
      (7.1+/-3.3) (P=.03). CONCLUSION: Conversion disorder tends to start in early
      adulthood, and usually follows a stress factor. As the duration of the disorder
      increases, comorbid psychopathologies, and the level of anxiety, and especially
      the prevalence of depression increase.

PMID- 12792843
TI  - The International Sepsis Forum 1st Annual Cambridge Colloquium on Genetic,
      Molecular, and Cellular Basis of Innate Immunity and Sepsis. Cambridge, United
      Kingdom, 14-15 July 2002. Proceedings.

PMID- 12792842
TI  - [Psychiatric and psychosocial aspects of chronic renal failure].
AB  - Primary treatment modalities of chronic renal failure (CRF) are dialysis and
      renal transplantation. According to 1997 data there were 10,000 hemodialysis and
      1893 continuous ambulatory peritoneal dialysis (CAPD) patients in Turkey. On a
      yearly basis 360 renal transplantation procedures take place. In deciding for one
      of the treatment modalities, medical criteria are of partial importance. On the
      other hand, in terms of psychosocial adjustment and functioning and quality of
      life, even the expert clinicians emphasize that is very difficult to predict
      which treatment modality is best for the patient. While some researchers report
      that psychiatric morbidity and disability of CRF are high and there is no
      difference between the chosen treatment modalities, most of them report that
      transplantation is more advantageous than dialysis, and quality of life is better
      in transplant patients. On the other hand, some researchers claim that
      psychological adjustment varies during the treatment of CRF and psychiatric
      symptoms decrease with time. In this paper, psychiatric and social problems in
      CRF and the effect of these problems on quality of life are reviewed. According
      to our literature review covering the past 30 years, there have been many
      researchers for the CRF patients' psychosocial difficulties. Also most of this
      research work compare treatment strategies with respect to psychiatric morbidity
      and quality of life.

PMID- 12792844
TI  - Use of transcriptome data to unravel the fine structure of genes involved in
      sepsis.
AB  - The sequence of the human genome is providing researchers with the scaffold upon
      which genes are built. The definition of the boundaries of the genes themselves
      and of their complex architecture requires a mapping of the transcriptome to the
      genome. A methodology was developed for generating a detailed transcriptome map
      and for reconstituting transcripts by using the genome as a template. As a
      demonstration of the potential of this method, the structure of the human Toll
      like receptor (TLR) genes was reevaluated. For all TLR genes for which a genomic
      sequence was available (i.e., all except TLR10), novel features of the gene
      structure were discovered. These features include multiple alternative
      polyadenylation sites, additional exons or splice variants, and overlaps with
      other genes. These findings have implications for the analysis of TLR gene
      expression and for the diversity of the proteins encoded by these genes.

PMID- 12792845
TI  - Quantitative proteome analysis: methods and applications.
AB  - With the completion of the genomic sequencing of a number of species, including
      that of humans, much attention is currently focused on how the information in
      these sequences might be interpreted in terms of the structure, function, and
      control of biologic systems and processes. Quantitative proteome analysis, the
      global analysis of protein expression, is increasingly being used as a method to
      study steady-state and perturbation-induced changes in protein profiles. The
      rationale for quantitative proteome analysis is described, along with a new
      technology for high throughput quantitative profiling of proteins in complex
      mixtures and its current status with selected applications.

PMID- 12792846
TI  - From phenomenon to phenotype and from phenotype to gene: forward genetics and the
      problem of sepsis.
AB  - Genetic tools (especially classical tools) have enlightened our understanding of
      biology as no other approach could. Mendel, Morgan, Bridges, and their heirs
      began with phenotypic traits and ended with genes. At first, the chemical
      identity of genes was not known, and even after years of methodologic refinement,
      more years of effort were needed to find the gene and the mutational difference
      that caused a particular phenotype. Chemistry has now outraced phenotypic
      analysis; all the genes are suddenly known, but most of their functions are not.
      The greatest challenge confronting all fields in biology is to establish
      correspondence between genes and discrete biologic functions. Sepsis is a
      devastating problem that has eluded a solution, despite the introduction of
      highly effective antimicrobial agents. Sepsis is an orchestrated process,
      understood in broad outline, but not in all details. Which genes are involved in
      the pathogenesis of sepsis? As in the golden age of genetics, the answer requires
      the solution of phenotypic puzzles, which, in turn, requires the creation of
      phenotypes.

PMID- 12792847
TI  - Drosophila melanogaster antimicrobial defense.
AB  - The Drosophila melanogaster host defense is complex but remarkably efficient. It
      is a multifaceted response to a variety of fungal, bacterial, and parasitic
      invaders. Current knowledge is discussed on recognition of infectious
      microorganisms and on the activation of intracellular signaling cascades that
      concur with the expression of numerous immune-responsive genes, among which, to
      date, the most prominent appear to encode potent antimicrobial peptides.

PMID- 12792848
TI  - Role of the mannose-binding lectin in innate immunity.
AB  - The ability to recognize infectious agents from self is intrinsic to innate
      immunity. One basic tenet of innate immunity is the evolution of classes of
      molecules that are termed "pattern-recognition" receptors and molecules. Many
      pattern-recognition molecules conspire together to protect the host in the first
      minutes and hours after exposure to an infectious challenge. The mannose-binding
      lectin (MBL; also termed "mannose-binding protein") is a prototypic pattern
      recognition molecule that appears to play a role as an "ante-antibody" in first
      line host defense. The serum levels of the human MBL are regulated in serum so
      that any one person will display a phenotype of low, intermediate, or high
      levels. There appears to be a relationship between circulating MBL and
      susceptibility and resistance to infection. MBL levels also appear to be
      regulated by distinct haplotypes. Thus, the question to be answered is what
      constitutes the innate immunity haplotype in any individual and how does this
      impact on the relationship between the host and infectious agents?

PMID- 12792849
TI  - Phagocytosis and the inflammatory response.
AB  - Macrophages are a cornerstone of the innate immune system. They detect infectious
      organisms via a plethora of receptors, phagocytose them, and orchestrate an
      appropriate host response. Phagocytosis is extraordinarily complex: numerous
      receptors stimulate particle internalization, the cytoskeletal elements mediating
      internalization differ by receptor system and the nature of the pathogen being
      internalized, and the outcome can differ by bacterium. After generating a panel
      of 150 monoclonal antibodies that recognizes proteins recruited to the phagosome,
      analysis of novel phagocytic proteins was prioritized by focusing on those that
      behave differently during the internalization of virulent and avirulent bacteria.
      Several novel proteins that have roles in membrane extension were characterized.
      Although the inflammatory pathways leading to appropriate host response are
      reasonably well defined, it is not clear how macrophages define the threat
      precisely. Recent work indicates that Toll-like receptors play a key role in
      reading a "bar code" on invading microorganisms and in eliciting a specific
      immune response. The mechanisms and coupling to the phagocytic response are
      discussed.

PMID- 12792850
TI  - The immune response is initiated by dendritic cells via interaction with
      microorganisms and interleukin-2 production.
AB  - The immune system of vertebrate animals is characterized by the capacity to
      respond to disturbances. This function requires 2 different approaches. First,
      the immune system responds in a few hours to infectious agents (innate immunity)
      by recognizing molecular patterns typical of microorganisms (but absent in self
      tissues). Second, it mounts a late response that differentiates among different
      microbes, giving rise to memory (adaptive immunity). In this context, dendritic
      cells (DCs) play a central role, becoming efficient stimulators of both innate
      and adaptive responses after microbial activation. Recent data generated by
      global transcriptional profiling of DCs after bacterial encounter are discussed,
      as are the unique DC functional plasticity and the central role of DC-derived
      interleukin-2 in priming early and late immune responses.

PMID- 12792851
TI  - Regulation of receptor-dependent activation of the innate immune response.
AB  - In the United States, >750,000 patients annually are thought to be at high risk
      for developing septic shock, with mortality rates reaching 60%. Thus, huge
      societal and financial costs are associated with this syndrome. Because of the
      high incidence and poor prognosis of septic shock, basic research has focused on
      the innate immune system for >2 decades. The pathophysiology of severe
      sepsis/shock is exceedingly complex, but there is little doubt that infection
      often progresses from systemic inflammatory response to severe sepsis and shock.
      Infection is the primary event in this sequence. There is evidence that the
      severity of the systemic reaction to infection (severe sepsis) is strongly
      influenced by the intensity of the inflammatory process at the infection sites.
      Efforts to understand the molecular mechanisms involved in recognition of
      bacterial products by members of the Toll-like receptor family are described, as
      well as some events that occur after receptor ligand binding that lead to new
      gene activation.

PMID- 12792852
TI  - Myeloid differentiation factor 88-dependent and -independent pathways in toll
      like receptor signaling.
AB  - Toll-like receptors (TLRs) play an essential role in the detection of invading
      pathogens in the body. Individual TLRs recognize distinct components derived from
      pathogens, which is followed by cytokine production. The TLR family harbors
      extracellular leucine-rich repeat domains and a cytoplasmic domain that is
      homologous to that of the interleukin (IL)-1 receptor (IL-1R) family. After
      stimulation, TLR recruits IL-1R-associated kinase via adaptor myeloid
      differentiation factor 88 (MyD88) and induces activation of NF-kappaB and mitogen
      activated protein kinases. Cytokine production in response to each TLR ligand is
      completely abrogated in MyD88-deficient cells, which indicates that MyD88 is an
      essential shared signaling molecule in the IL-1R/Toll family. The TLR4 signal has
      an MyD88-independent pathway that is involved in induction of type I interferons
      (IFNs) and IFN-inducible genes via IFN regulatory factor-3 activation. A recently
      identified adaptor molecule, Toll-IL receptor domain-containing adaptor
      protein/MyD88 adaptor-like, may participate in the MyD88-independent pathway.

PMID- 12792853
TI  - Nuclear factor-kappaB and its role in sepsis-associated organ failure.
AB  - Nuclear factor (NF)-kappaB is involved in regulating the transcription of many of
      the immunomodulatory mediators involved in the development of sepsis-induced
      organ failure. Kinase pathways involving p38 and Akt and initiated by engagement
      of Toll-like receptors modulate transcriptional activity of NF-kappaB, but
      apparently through different mechanisms. Increased activation of NF-kappaB occurs
      with sepsis, and greater levels of nuclear accumulation of NF-kappaB are
      associated with higher rates of mortality and worse clinical outcome. The
      percentage of apoptotic neutrophils is reduced in sepsis, and inhibition of
      nuclear translocation of NF-kappaB restores neutrophil apoptosis to baseline
      levels. In models of sepsis, suppression of NF-kappaB activation decreases acute
      inflammatory processes and organ dysfunction. Because NF-kappaB occupies a
      central role in signaling pathways important in sepsis, modulation of NF-kappaB
      activity may be an appropriate therapeutic target in patients with sepsis.

PMID- 12792854
TI  - Interleukin-18 and host defense against infection.
AB  - Interferon (IFN)-gamma-inducing factor was previously termed interleukin (IL)-18.
      Although IL-12 is also an IFN-gamma-inducing factor, the activity of IL-18 (but
      not IL-12) in models of sepsis and death is dependent on the intracellular
      cysteine protease IL-1beta converting enzyme (caspase-1). Caspase-1 is required
      for cleavage of the inactive precursor form of IL-18 into an active cytokine, and
      caspase-1-deficient mice are resistant to lethal endotoxemia. The absence of IFN
      gamma (but not IL-1beta) in caspase-1-deficient mice is responsible for this
      resistance. However, the role of IFN-gamma in murine defense against gram
      negative infection is inconsistent. Mice deficient in IFN-gamma are not resistant
      to lethal endotoxemia but are resistant when treated with neutralizing antibodies
      to IL-18 and challenged with a lethal injection of some endotoxins. Anti-IL-18
      treatment also reduces neutrophil accumulation in liver and lungs. Neutralizing
      IL-18 with the IL-18 binding protein protects mice against endotoxin- and
      ischemia-induced hepatic damage. Thus, blockade of IL-18 appears to be a viable
      clinical target to combat the pathologic consequences of sepsis via IFN-gamma
      mechanisms.

PMID- 12792855
TI  - Macrophage migration inhibitory factor and host innate immune defenses against
      bacterial sepsis.
AB  - Macrophages are essential effector cells of innate immunity that play a pivotal
      role in the recognition and elimination of invasive microorganisms. Mediators
      released by activated macrophages orchestrate innate and adaptive immune host
      responses. The cytokine macrophage migration inhibitory factor (MIF) is an
      integral mediator of the innate immune system. Monocytes and macrophages
      constitutively express large amounts of MIF, which is rapidly released after
      exposure to bacterial toxins and cytokines. MIF exerts potent proinflammatory
      activities and is an important cytokine of septic shock. Recent investigations of
      the mechanisms by which MIF regulates innate immune responses to endotoxin and
      gram-negative bacteria indicate that MIF acts by modulating the expression of
      Toll-like receptor 4, the signal-transducing molecule of the lipopolysaccharide
      receptor complex. Given its role in innate immune responses to bacterial
      infections, MIF is a novel target for therapeutic intervention in patients with
      septic shock.

PMID- 12792856
TI  - High mobility group box-1 as a therapeutic target downstream of tumor necrosis
      factor.
AB  - The discovery of tumor necrosis factor (TNF) as a necessary and sufficient
      mediator of systemic inflammation started a new field of research to rationally
      modulate cytokine responses to therapeutic advantage. However, the early kinetics
      of the TNF response during infection defined an extremely narrow window of
      opportunity during which anti-TNF therapeutics are efficacious, hampering
      clinical development for severe sepsis. Because death from severe sepsis often
      occurs as a late phenomenon, we began a search began for putative "late"
      mediators that could be targeted after the onset of infection. We have now
      identified high mobility group box-1 (HMGB1) as a late mediator of endotoxemia
      and sepsis. HMGB1 is released by activated macrophages, induces the release of
      other proinflammatory mediators, and mediates lethality when overexpressed.
      Administration of anti-HMGB1 antibodies inhibit systemic inflammation, even in
      established cases, because HMGB1 activity is elevated at significantly later time
      points than TNF or interleukin-1. It will now be important to determine whether
      this wider window of activity can be translated into therapeutic advantage for
      human inflammatory disease.

PMID- 12792857
TI  - TREM-1 (triggering receptor expressed on myeloid cells): a new player in acute
      inflammatory responses.
AB  - TREM-1 (triggering receptor expressed on myeloid cells), a recently discovered
      receptor of the immunoglobulin superfamily, activates neutrophils and
      monocytes/macrophages by signaling through the adapter protein DAP12. TREM-1 is
      the best-characterized member of a growing family of DAP12-associated receptors
      that regulate the function of myeloid cells in innate and adaptive responses.
      TREM-1 amplifies Toll-like receptor-initiated responses against microbial
      challenges and potentiates the secretion of proinflammatory chemokines and
      cytokines in response to bacterial and fungal infections. Blockade of TREM-1
      reduces inflammation and increases survival in animal models of bacterial
      infections that cause systemic hyperinflammatory syndromes. The TREM-1 ligands
      are not known. Characterization of TREM-1 natural ligands will further illuminate
      the mechanisms regulating innate responses against pathogens. Whatever the
      ligands, targeted activation or blockade of TREM-1 and its ligands may help
      maximize the efficacy of existing treatments for sepsis.

PMID- 12792858
TI  - Combination therapy for aspergillosis: is it needed, and which combination?

PMID- 12792859
TI  - Combination therapy in treatment of experimental pulmonary aspergillosis:
      synergistic interaction between an antifungal triazole and an echinocandin.
AB  - Invasive pulmonary aspergillosis is an important cause of morbidity and mortality
      in immunocompromised patients. Simultaneous inhibition of fungal cell-wall and
      cell-membrane biosynthesis may result in synergistic interaction against
      Aspergillus fumigatus. We studied the antifungal activity of micafungin, a new
      echinocandin, in combination with ravuconazole, a second-generation triazole,
      against experimental invasive pulmonary aspergillosis in persistently neutropenic
      rabbits. This combination led to significant reductions in mortality (P</=.001),
      residual fungal burden (P</=.05), and serum galactomannan antigenemia (P</=.01),
      compared with either agent alone. Combination therapy also resulted in reduction
      (P</=.05) of organism-mediated pulmonary injury and of pulmonary infiltrates
      detected by thoracic computed tomography (P</=.001). No toxicity was observed
      with the echinocandin-triazole combination. An MTT hyphal damage assay
      demonstrated significant in vitro synergistic interaction between the antifungal
      triazole and the echinocandin. The combination of an antifungal triazole and
      echinocandin may represent a new strategy for treatment of invasive pulmonary
      aspergillosis.

PMID- 12792861
TI  - Identification of immunoreactive proteins during acute human giardiasis.
AB  - The protozoan Giardia lamblia is a major cause of parasite-induced diarrhea in
      humans. Humoral immunity has been shown to be important for clearance of the
      infection, but only a few antigens have been identified. In this study, we
      focused on the immunoreactivity of nonvariant antigens. Serum samples from 93
      patients with acute giardiasis who were infected during a waterborne outbreak in
      a nonendemic country were screened on 1-dimensional Western blots. Representative
      serum samples that reacted strongly with proteins of different molecular weights
      were further analyzed on 2-dimensional Western blots. Sixteen immunoreactive
      proteins were identified using mass spectrometry analysis, among them variable
      surface proteins, alpha-giardins, arginine deiminase, ornithine carbamoyl
      transferase, and fructose-1,6-bisphosphate aldolase. Several of the identified
      proteins were immunoreactive in recombinant form, and they may be important in
      the development of new diagnostic tools and vaccines.

PMID- 12792860
TI  - Quantitation of anti-Pneumocystis jiroveci antibodies in healthy persons and
      immunocompromised patients.
AB  - To facilitate studies of the epidemiology of Pneumocystis jiroveci infection in
      both healthy persons and immunocompromised patients, we developed a quantitative
      ELISA with recombinant major surface glycoprotein (MSG) fragment MSG-14, a P.
      jiroveci-specific protein that includes a highly conserved region of the MSG
      protein family. By immunoblot, all samples reacted with the carboxyl portion of
      MSG-14; by ELISA, immunocompromised patients with Pneumocystis pneumonia (PCP)
      who were immunocompromised for reasons other than AIDS had higher antibody levels
      than did either patients with AIDS with PCP (P=.01) or healthy persons (P=.005).
      Longitudinal observations of 8 patients with AIDS showed no correlation between
      time of diagnosis of Pneumocystis infection and change in antibody levels. Eleven
      percent (4/35) of healthy persons demonstrated a >4-fold change in antibody
      titers during 1 year of observation. This ELISA assay allows quantitation of anti
      P. jiroveci antibodies in human serum samples and should be useful in better
      understanding the epidemiology of P. jiroveci infection in humans.

PMID- 12792862
TI  - Genotyping of Entamoeba species in South Africa: diversity, stability, and
      transmission patterns within families.
AB  - Using a recently described polymerase chain reaction-based DNA typing method for
      Entamoeba histolytica and E. dispar, we investigated the genetic diversity of
      these species in a geographically restricted region of South Africa. Patterns
      were stable over time in the same infection, and, with few exceptions, infected
      family members carried the same strain. However, both species exhibited
      remarkable variation, with no 2 family groups being infected with the same strain
      of E. histolytica. Mixed infections were rare. The results indicate that this
      typing method will be useful in identifying epidemiological linkage between
      infections.

PMID- 12792863
TI  - Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after
      cessation of chloroquine use in Malawi.
AB  - In 1993, Malawi became the first African country to replace chloroquine with
      sulfadoxine-pyrimethamine nationwide in response to high rates of chloroquine
      resistant falciparum malaria. To determine whether withdrawal of chloroquine can
      lead to the reemergence of chloroquine sensitivity, the prevalence of the pfcrt
      76T molecular marker for chloroquine-resistant Plasmodium falciparum malaria was
      retrospectively measured in Blantyre, Malawi. The prevalence of the chloroquine
      resistant pfcrt genotype decreased from 85% in 1992 to 13% in 2000. In 2001,
      chloroquine cleared 100% of 63 asymptomatic P. falciparum infections, no isolates
      were resistant to chloroquine in vitro, and no infections with the chloroquine
      resistant pfcrt genotype were detected. A concerted national effort to withdraw
      chloroquine from use has been followed by a return of chloroquine-sensitive
      falciparum malaria in Malawi. The reintroduction of chloroquine, ideally in
      combination with another antimalarial drug, should be considered in areas where
      chloroquine resistance has declined and safe and affordable alternatives remain
      unavailable.

PMID- 12792864
TI  - Quantitative and qualitative comparison of virulence traits, including murine
      lethality, among different M types of group A streptococci.
AB  - Epidemiological studies have proposed an association between group A streptococci
      (GAS) bearing a particular M serological type and pathologic conditions such as
      streptococcal toxic shock syndrome (STSS). M1 and M3 GAS are isolated from STSS
      cases more frequently, whereas M4 and M12 GAS are isolated from non-STSS cases
      more frequently. To investigate whether there is any difference contributing the
      M-type association among GAS, we compared various virulence traits, including the
      murine lethality of M4, M12, M1, and M3 GAS clinical isolates, which are not
      clonally related to one another. Murine lethality, the activities of
      superantigens, streptolysin O, and nicotinamide adenine dinucleotide
      glycohydrolase, and the presence of the speA and speC genes were closely
      associated with M type. These results indicate that M types may serve, in part,
      as markers for strains/clones with particular profiles of virulence traits and
      mouse lethality.

PMID- 12792865
TI  - Recombinant or peptide antigens in the serology of Lyme arthritis in children.
AB  - The performance of ELISAs with the recombinant antigens decorin-binding protein A
      (DbpA), DbpB, and BBK32 (from Borrelia afzelii, B. garinii, and B. burgdorferi
      sensu stricto) and VlsE peptide antigen invariable region 6 (IR(6)) were
      evaluated in the serodiagnosis and follow-up of children with Lyme arthritis
      (LA). Serum samples were obtained from 52 children with clinically typical and
      serologically confirmed LA. In IgG ELISAs, at diagnosis, 50 samples were positive
      for BBK32, 51 for DbpA, 40 for DbpB, and 51 for IR(6). In the posttreatment
      follow-up, the rate of decline of the antibodies to the recombinant protein
      antigens or to IR(6) did not appear useful in the prediction of the treatment
      response or the clinical course of LA. Yet, IR(6) seems to have the greatest
      potential to be used universally in the diagnostic serology of Lyme borreliosis
      (LB). Alternate to that, the use of several specific borrelial antigens, in
      parallel, might improve the accuracy of serology for LB.

PMID- 12792866
TI  - Molecular analysis and experimental virulence of French and North American
      Escherichia coli neonatal meningitis isolates: identification of a new virulent
      clone.
AB  - Phylogenetic relationships, virulence factors, alone and in specific
      combinations, and virulence in a rat meningitis model were examined among 132
      isolates of Escherichia coli neonatal meningitis from France and North America.
      Isolates belonging to phylogenetic groups A (n=11), D (n=20), and B2 (n=99) had
      similar high prevalence rates of the siderophores aerobactin and yersiniabactin
      and the K1 capsule (>/=70%) yet induced different level of experimental
      bacteremia. Ectochromosomal DNA-like domains involved in blood-brain barrier
      passage (PAI III(536) [sfa/foc and iroN; 34%]; GimA [ibeA and ptnC; 38%]; PAI
      II(J96) [hly, cnf1, and hra; 10%]) were restricted to B2 isolates. Among group B2
      isolates, representatives of the O45:K1 clonal group (n=30), which lacked these
      domains, were as able as the archetypal O18:K1 strain C5 to cause meningitis.
      Molecular epidemiology combined with experimental virulence assays demonstrate
      that known virulence factors are insufficient to fully explain the
      pathophysiology of ECNM and to allow for rational search for new virulence
      factors.

PMID- 12792868
TI  - Immunological and virological failure after antiretroviral therapy is associated
      with enhanced peripheral and thymic pathogenicity.
AB  - T cell dynamics and viral genotype were studied in human immunodeficiency virus 1
      infected individuals receiving antiretroviral therapy who were viremic and had
      either increasing (discordant immunological responders) or decreasing
      (nonresponders) CD4(+) T cell counts. A comparison was made with treated
      individuals who were not viremic and had increasing CD4(+) T cell counts
      (complete responders). Nonresponders had higher CD4(+) T cell proliferation (as
      assessed by Ki67 expression) and immune activation (as assessed by CD38 and human
      leukocyte antigen-DR expression), together with a reduction in T cell receptor
      excision circles, compared with discordant immunological responders and complete
      responders, which suggests that there is enhanced viral pathogenicity in both
      peripheral T cells and the thymus. Although there was a high prevalence of
      mutations in the protease and reverse transcriptase genes in discordant
      immunological responders, these changes were also observed in nonresponders.

PMID- 12792867
TI  - Acquisition of stcE, a C1 esterase inhibitor-specific metalloprotease, during the
      evolution of Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 is a source of foodborne illness, causing diarrhea,
      hemorrhagic colitis, and hemolytic-uremic syndrome. E. coli O157:H7 secretes, via
      the etp type II secretion system, a metalloprotease, StcE, that specifically
      cleaves the serpin C1 esterase inhibitor. We determined by hybridization
      techniques the prevalence of stcE and etpD, a type II secretion gene, among
      diarrheagenic E. coli strains. stcE and etpD are ubiquitous among the O157:H7
      serotype and are found in some enteropathogenic E. coli O55:H7 strains but are
      absent from other diarrheagenic E. coli. stcE was acquired on a large plasmid
      early in the evolution of E. coli O157:H7, before the inheritance of the Shiga
      toxin prophage. Other plasmidborne virulence factors, such as ehxA, katP, and
      espP, were acquired later by the enterohemorrhagic E. coli 1 complex in a
      stepwise manner. These data refine the sequential model of E. coli O157:H7
      evolution proposed elsewhere.

PMID- 12792871
TI  - Evidence for a recessive major gene predisposing to human herpesvirus 8 (HHV-8)
      infection in a population in which HHV-8 is endemic.
AB  - Infection by human herpesvirus 8 (HHV-8), as measured by the presence of specific
      antibodies, was shown in countries in which HHV-8 infection is endemic to exhibit
      familial aggregation and a peculiar variation with age (rapid increase until
      puberty followed by a plateau in young adults). To investigate whether host
      genetic factors could explain these findings, a segregation analysis was
      performed of 81 families of African origin (1623 subjects; HHV-8 seroprevalence,
      11.9%) living in a village in French Guiana in which HHV-8 infection is endemic.
      Results provide evidence for a recessive gene controlling susceptibility or
      resistance to HHV-8 infection. This gene is predicted to have a major effect
      during childhood, with almost all homozygous predisposed subjects ( approximately
      6% of the population) being infected by age 15. For nonpredisposed subjects, HHV
      8 infection in childhood strongly depends on virus exposure (through an HHV-8
      infected mother), whereas the risk of infection appears to be low in young
      adults, with no evidence for heterosexual transmission.

PMID- 12792869
TI  - Age-related immune dysfunction in health and in human immunodeficiency virus
      (HIV) disease: association of age and HIV infection with naive CD8+ cell
      depletion, reduced expression of CD28 on CD8+ cells, and reduced thymic volumes.
AB  - Older age is a strong predictor of accelerated human immunodeficiency virus (HIV)
      disease progression. We investigated the possible immunologic basis of this
      interaction by comparing older (>/=45 years) and younger (</=30 years) HIV
      infected adults with simultaneously enrolled, aged-matched, healthy volunteers.
      Cross-sectional comparisons suggested age-associated reductions in naive CD8(+)
      cells and in the expression of CD28(+) on CD8(+) cells among both HIV-infected
      subjects and control subjects. Opposite patterns of CD4(+) and CD8(+) cell
      differences were apparent between these subject groups. HIV infection, but not
      age, was associated with impairments in delayed-type hypersensitivity responses,
      lymphoproliferation, and spontaneous apoptosis and with alterations in expression
      of chemokine receptors CCR5 and CXCR4. Reduced thymic volumes were associated
      with age and with HIV infection among younger, but not older, subjects. Because
      of their common association with age and HIV disease, naive CD8(+) cell
      depletion, diminished CD28 expression on CD8(+) cells, and reduced thymic volumes
      are possible correlates of the interaction of age with HIV disease.

PMID- 12792870
TI  - Variable prediction of antiretroviral treatment outcome by different systems for
      interpreting genotypic human immunodeficiency virus type 1 drug resistance.
AB  - To determine the variability of genotypic human immunodeficiency virus (HIV) type
      1 drug-resistance interpretation by available expert systems and its clinical
      implications, 261 subjects for whom a potent antiretroviral regimen was failing
      who were starting salvage therapy were evaluated. The association of the
      genotypic susceptibility score (GSS) of the salvage regimen, according to 11
      interpretation systems, with HIV RNA outcomes for 6 months was examined. GSS was
      highly variable, as determined by the different interpretation systems, and
      showed independent correlation with changes from baseline HIV RNA levels at 6
      months with 5 systems--Stanford hivdb, GuideLines 3.0, Retrogram 1.4,
      HIVresistanceWeb, and Sao Paulo University. Most GSSs predicted virologic
      response in regimens containing stavudine, lamivudine, efavirenz, or indinavir.
      Selected systems predicted response in regimens containing didanosine, abacavir,
      or nelfinavir, and no system predicted outcome of boosted protease inhibitors.
      GSSs predicted changes in HIV RNA levels better in adherent patients than in
      nonadherent individuals. Interpretation may be improved, and knowledge should be
      used uniformly throughout different expert systems.

PMID- 12792872
TI  - Evidence of viral replication in circulating dendritic cells during hepatitis C
      virus infection.
AB  - The existence of extrahepatic sites of hepatitis C virus (HCV) replication has
      been proposed as a mechanism responsible for the poor antiviral immune response
      found in chronic infection. Dendritic cells (DCs), as unique antigen-presenting
      cells able to induce a primary immune response, are prime targets of persistent
      viruses. From 24 blood samples obtained from HCV-seropositive patients,
      peripheral blood DCs (PBDCs) were purified. HCV genomic sequences were
      specifically detected by reverse-transcription polymerase chain reaction in 6 of
      24 PBDC pellets, and replicative-strand RNA also was found in 3 of 24 cell
      purifications. Analysis of the HCV quasi-species distribution in the PBDC
      population of 1 patient showed the presence of a dominant variant different from
      that found in plasma with respect to the primary amino-acid sequence and
      physicochemical profile of the hypervariable region 1 of glycoprotein E2. These
      data strongly suggest that PBDCs constitute a reservoir in which HCV replication
      takes place during natural infection.

PMID- 12792873
TI  - Field trial of a vaccine against new world cutaneous leishmaniasis in an at-risk
      child population: how long does protection last?
AB  - During 12 months of follow-up in a randomized double-blind controlled field
      study, a killed whole-promastigote vaccine cocktail plus bacille Calmette-Guerin
      (BCG) adjuvant significantly reduced the incidence of cutaneous leishmaniasis
      (CL) in Ecuadorian children, compared with BCG alone. To determine how much
      longer protection might continue, the study was reblinded to permit 48 additional
      months of follow-up. During months 13-18, CL incidence remained lower in the
      vaccine group, compared with that in the control group (5.9% vs. 13.8%; chi2=8.8;
      P=.003), with vaccine efficacy calculated at 56.5% (95% confidence interval,
      18.7%-76.7%); however, during months 24-60, no significant between-group
      differences were detected. Periodic administration of boosters may be necessary
      to maintain whole-parasite-vaccine protection against New World CL.

PMID- 12792874
TI  - Lethal invasive cestodiasis in immunosuppressed patients.
AB  - Using both traditional methods and broad-range 18S ribosomal DNA (rDNA)
      polymerase chain reaction, we examined 2 cases of lethal cestodiasis, in which
      the disease agent had been poorly identified or misidentified. In one case,
      involving a patient with AIDS, we identified the human dwarf tapeworm,
      Hymenolepis nana, as a cause of aberrant metastatic larval disease. In the second
      case with similar pathologic abnormalities, involving a patient with Hodgkin
      disease, we identified a larval cestode with a previously uncharacterized 18S
      rDNA sequence. A prior report of this case nearly 30 years ago, based on tissue
      examination, had suggested that the parasite was a sparganum.

PMID- 12792876
TI  - Mitochondrial:nuclear DNA ratios in peripheral blood cells from human
      immunodeficiency virus (HIV)-infected patients who received selected HIV
      antiretroviral drug regimens.
AB  - Mitochondrial:nuclear DNA (mtDNA:nDNA) ratios in blood cells were investigated in
      relation to selected human immunodeficiency virus antiretroviral drug regimens.
      Patients (n = 214) continually received a regimen consisting of either (1)
      saquinavir (SAQ) + ritonavir (RTV) + either nevirapine (NVP) or lamivudine (3TC)
      (n=32) or (2) SAQ+RTV (+/- either NVP or 3TC) + either stavudine (d4T) (n=127),
      didanosine (ddI) (n=19), d4T+ddI (n=21), or zidovudine (ZDV) (n=15), for >/=4
      months. NVP- or 3TC-only regimens were associated with median mtDNA:nDNA ratios
      that were significantly higher than those for ddI- and d4T+ddI-containing
      regimens (P<.01) but that were not significantly higher than those for d4T- or
      ZDV-containing regimens. Patients received thymidine analogue- and/or ddI
      containing regimens for a shorter time (median, 14 vs. 24 months; P<.01). Because
      of survivor-bias effect, these results may represent a conservative estimate of
      these nucleosides' effect on mtDNA.

PMID- 12792875
TI  - Human immunodeficiency virus-1 RNA levels and CD4 lymphocyte counts, during
      treatment for active tuberculosis, in South African patients.
AB  - During 6 months of treatment, we measured human immunodeficiency virus (HIV)-1
      virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1
      infected patients with active tuberculosis (TB). The median virus load (baseline,
      5.58 log(10) copies/mL) significantly increased at 1 month (5.71 log(10)
      copies/mL), then returned to near-baseline levels at 3 months (5.40 log(10)
      copies/mL) and at 6 months (5.36 log(10) copies/mL). In contrast, the median CD4
      counts increased at 1 month (186/mm(3)), at 3 months (238/mm(3)), and at 6 months
      (239/mm(3)). CD4 counts and virus loads did not change during therapy. Expression
      of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of
      interleukin-6 decreased over time.

PMID- 12792877
TI  - Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to
      macrolide-containing regimens for treatment of Mycobacterium avium disease.
AB  - Macrolides are the core of effective drug regimens for the treatment of
      Mycobacterium avium complex (MAC) disease. Mefloquine (MFQ), moxifloxacin (MXF),
      and ethambutol (EMB), in combination, were evaluated against both clarithromycin
      resistant (CLR-R) and CLR-susceptible (CLR-S) MAC; MFQ (40 mg/kg), MXF (100
      mg/kg), or EMB (100 mg/kg/day) was given to mice for 4 weeks. MFQ was
      bactericidal, whereas MXF and EMB were bacteriostatic against both MAC 101 CLR-S
      and CLR-R. The combination of MFQ and EMB reduced (P<.05, for comparison with
      controls), and the combination of MFQ and MXF significantly reduced, the load of
      CLR-R in both the liver and the spleen. Treatment with all 3 drugs was associated
      with approximately 1-log reduction of CLR-R after 1 week, 2.1-log reduction of
      CLR-R after 4 weeks, and 2.17-log reduction in MAC/mL blood. Treatment of MAC 101
      CLR-S strain had comparable results.

PMID- 12792878
TI  - Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in pituitary tumours.
AB  - The present study was performed to investigate HIF-1alpha (hypoxia-inducible
      factor-1alpha) expression in a large number of immunohistochemically and
      ultrastructurally characterized surgically removed pituitary tumours. The
      potential relation of HIF-1alpha with outcome variables as well as the presence
      of HIF-1alpha expression in the tumours treated with dopamine agonists and
      octreotide, a long-acting somatostatin analogue was also investigated. HIF-1alpha
      immunoreactivity was confined to the nucleoplasm whereas the nucleoli were
      unconspicuous. The distribution of HIF-1alpha was evident in the tumours whereas
      normal adenohypophysial cells showed no HIF-1alpha staining. HIF-1alpha
      expression was detected not only in the tumour cells but also in endothelial
      cells lining the blood vessels within the tumour. ACTH producing adenomas showed
      the lowest level of HIF-1alpha expression whereas pituitary carcinomas and GH
      producing adenomas had the highest counts. The statistical study demonstrated no
      significant correlation between HIF-1alpha expression, patient age, gender,
      tumour, size, invasiveness, cell proliferation rate and vascularity. These
      results suggest that the behaviour of pituitary tumours does not primarily depend
      of HIF-1alpha expression. Our study demonstrated an increase HIF-1alpha
      expression in bromocriptine treated PRL producing pituitary adenomas compared
      with untreated tumours but no increase in octreotide treated tumours.

PMID- 12792879
TI  - Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and
      differentiation in astrocytic glioma cells in culture.
AB  - Gamma-glutamyltransferase (GGT) hydrolyses gamma-glutamylated peptides, including
      glutathione and transports amino acids into the cells. The enzyme is up-regulated
      in some tumors, especially those with a higher degree of malignancy and
      resistance to cytostatics. In this study we examined the effects of Cisplatin
      (1.6 x 10(-5)M) on the activity of GGT in astrocytic C6 glioma cells in cultures
      monitored for growth, morphology and differentiation. Initially (24 h), the drug
      inhibited cell division and later (96 h), it caused apoptotic death of about half
      of the population. The more resistant and surviving cells became hypertrophic and
      more differentiated, as indicated by their larger size and higher protein
      content, including the maturation- specific GFAP. In addition, the activity of
      GGT was significantly elevated in these cells at 48 h and onwards. At 96 h, the
      biochemically determined enzyme activity was between 230% and 330% above the
      controls. Compared to the protein content, the GGT activity started to increase
      later (48 h) but it grew steeper towards 72-96 h. Similarly, histochemical
      analysis revealed a manifold increase in the number of GGT+ cells in the
      population and higher intensity of staining per cell from at 48 h and onwards.
      The study showed that the transformed astrocytic cells can up-regulate GGT
      activity as part of an adaptation and/or, survival-enhancing reaction triggered
      by Cisplatin.

PMID- 12792880
TI  - Modulatory role of IL10 in endothelial cell damage and platelet adhesion.
AB  - This study explores the possibility of a regulatory role for cytokine IL-10 in
      platelet aggregation as an active vascular repair mechanism. Endothelial cells
      from human umbilical cord vein were cultured in the presence of different IL-10
      concentrations (0-100 ng/ml). Platelet-rich plasma was then added to these
      cultures and allowed to act for 30 minutes. To rule out blood plasma involvement,
      washed platelets were also incubated with IL-10 (0-100 ng/ml). Changes in
      endothelial cell morphology were observed depending on the IL-10 concentration
      used; apoptotic cells appearing at the highest IL-10 concentration. Greatest
      platelet adhesion was noted at the highest IL-10 concentration. It was concluded
      that, in this in vitro model, low IL-10 levels do not affect cell viability or
      the pattern of platelet adhesion, but at high doses, this cytokine induces cell
      death and enhances platelet deposition.

PMID- 12792881
TI  - Ultrastructural evaluation of the effect of endosulfan on mice kidney.
AB  - In this study, the effect of the endosulfan on mice kidney was investigated at
      ultrastructural level. Moreover, biochemical analyses (G6PD, CAT, SOD, GSH and
      MDA) were determined in supernatant of kidney tissue. Endosulfan (13mg/kg/day
      body weight) was administered orally to mices via intragastric-during 10 days.
      The presence of mitochondrial degeneration in cytoplasm of proximal convoluted
      tubule cells were a striking feature. Furthermore, there was lipofuscin granules
      and membranous structures in some of proximal convoluted tubule cells. In some
      glomeruli, ultrastructural changes such as fusion in pedicels and focal
      thickening at glomerular basal membrane were seen. There were cytoplasmic bulges
      in some distal convoluted tubule cells. The biochemical results of the
      experimental group were significant when compared to the control. The effect of
      the endosulfan was mainly on the proximal convoluted tubule cells. Morever, the
      other parts of the nephron were effected. Thus, this degeneration in kidney may
      be thought that oxidative stress may play a role to the mediator in changing
      configuration of cell membrane and seem to account for the morphologic alteration
      of kidney.

PMID- 12792882
TI  - Morphometric analysis of the tumor associated tissue eosinophilia in the oral
      squamous cell carcinoma using different staining techniques.
AB  - In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a
      favourable prognostic indicator for oral squamous cell carcinomas. Special
      techniques such as autofluorescence or immunohistochemistry are reported to be
      sometimes necessary to detect the presence of intact and degranulating
      eosinophils within the tumors. The aim of this study was to compare the number of
      eosinophils identified routinely with hematoxylin and eosin stain and by
      immunohistochemistry in oral squamous cell carcinomas with TATE. Thirty specimens
      of oral squamous cell carcinoma of the tongue, floor of the mouth, retromolar
      area and inferior gingiva with TNM stages II and III were used for
      histopathological analysis. Three-micrometer sections were stained with
      hematoxylin and eosin and immunohistochemically with monoclonal anti-human
      granulocyte-associated antigen using a standard streptavidin-biotin-peroxidase
      complex technique. The number of eosinophils/mm2 in the invasive front of the
      tumors was automatically quantified in a x400 field using an image computer
      analyser. Univariate statistical analysis was carried out using Student's t test.
      The computer-assisted morphometric results showed that there was no statistically
      significant difference (p>0.05) in the number of eosinophils/mm2 identified by
      hematoxylin and eosin or immunostaining technique in oral squamous cell
      carcinomas with TATE. This result suggests that hematoxilyn and eosin routine
      stain is a useful technique for measuring eosinophils in squamous cell carcinoma
      with eosinophilic tumor infiltration.

PMID- 12792884
TI  - The influence of different fibrous supplements in the diet on ruminal histology
      and histometry in veal calves.
AB  - The aim of this study was to determine whether the administration of four
      different solid feeds would influence selected morphological and morpho
      functional aspects of the rumen mucosa in veal calves. The fibrous
      supplementation of the liquid diet of veal calves has been provided by recent EU
      formulation (EC Council Directive 91/629/1991; EC Council Directive 97/2/1997).
      Twenty-five Holstein calves were assigned to either exclusively liquid diet (milk
      replacer, control), or pelleted feed, corn silage, extruded feed, dried corn
      silage. The morpho-functional effects of the fibre-containing diets were examined
      evaluating histological and histometrical characteristics of ruminal mucosa after
      the slaughter of calves. There were slight to severe histological abnormalities
      in the rumens of all animals examined. The severe histological abnormalities were
      present in calves given pelleted feed, corn silage, and extruded feed. Dried corn
      silage caused less ruminal damage. We found that the length and epithelial
      thickness of ruminal papillae were higher in control veal calves than in dietary
      fibre-supplemented animals. The results of the present study, even if partially,
      support the EU prescription in the use of fibre diets in veal calves as
      integration of the traditional milk replacer diet.

PMID- 12792883
TI  - Endostatin induces autophagic cell death in EAhy926 human endothelial cells.
AB  - Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of
      angiogenesis and suppresses neovascularization and tumor growth. However, the
      inhibitory mechanism of endostatin in human endothelial cells has not been
      characterized yet. Electron microscopic analysis revealed that endostatin induced
      formation of numerous autophagic vacuoles in endothelial in 6 to 24 h after
      treatment. Moreover, there was only a 2- to 3-fold increase in intracellular
      reactive oxygen species after endostatin treatment. Endostatin-induced cell death
      was not prevented by antioxidants (vitamin C, vitamin E, or propyl gallate) or
      caspase inhibitors, suggesting that the increase of oxidative stress or the
      activation of caspases may not be the crucial factors in the anti-angiogenic
      mechanism of endostatin. However, the cytotoxicity of endostatin was
      significantly reduced by 3-methyladenine (a specific inhibitor of autophagy) and
      serine and cysteine lysosomal protease inhibitors (leupeptin and aprotinin).
      Taken together, these results suggest that in human endothelial cells: (1)
      endostatin predominantly causes autophagic, rather than apoptotic, cell death,
      (2) endostatin-induced autophagic cell death occurs in the absence of caspase
      activation and through an oxidative-independent pathway, and (3) endostatin
      induced "autophagic cell death" or "type 2 physiological cell death" is regulated
      by serine and cysteine lysosomal proteases.

PMID- 12792885
TI  - Lectin binding in the human foetal testis.
AB  - In the present study we have investigated the oligosaccharidic content of the
      glycoconjugates within the human foetal testis starting from its earliest
      differentiation phase (8, 10 and 12 weeks of gestation). To this purpose we have
      used a battery of six horseradish peroxidase-labelled lectins (SBA, PNA, WGA,
      UEAI, LTA and ConA). We have obtained a complete distributional map of the sugar
      residues of the glycoconjugates in the coelomic mesothelium, tunica albuginea,
      pre-Sertoli cells, pre-gonocytes, Leydig cells, basement membrane of the sex
      cords, interstitial tissue, mastocytes and endothelial cells of the capillary
      vessels. Since the beginning of the testis differentiation phase the cells of the
      coelomic mesothelium showed a large amount of sugar residues. In the pre-Sertoli
      cells and in the pre-gonocytes a role played as structural molecules by some
      oligosaccharides could be hypothesized. D-galactose-(beta1-->3)-N-acetyl-D
      galactosamine, sialic acid, N-acetyl-D-glucosamine and alpha-D-mannose could be
      involved in inducing and maintaining the cellular activity of the Leydig cells.

PMID- 12792886
TI  - Adenomatous hyperplasia of the rete testis. A review and report of new cases.
AB  - Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon benign lesion
      that preferentially involves the septal rete testis and mediastinal rete testis.
      It is usually an incidental finding in surgical specimens from cryptorchidism and
      testicular tumour. It can be found in autopsy specimens from patients dying with
      different chronic diseases and newborns with kidney diseases. Since its first
      description many articles have been published communicating new cases and putting
      forward some hypotheses on its aetiology and pathogenic mechanisms. Some authors
      suggest a role for hormonal changes, tumour invasion and action of chemical
      agents. We think that AHRT should be categorised into two main aetiological
      categories: congenital and acquired. The cases associated with different kidney
      and spermatic duct diseases, most cases associated with cryptorchidic testis and
      some cases associated with testicular germ cell tumour should be included in the
      congenital group. The remaining cases associated with chemical agents, some
      hormonal changes (i.e. androgen blockade) and most of the germ cell tumour cases
      can be considered as acquired AHRT. Differential diagnosis must be established
      mainly with metastatic adenocarcinoma of prostate to testis and primary
      adenocarcinoma of the rete testis. Pseudohyperplasia of the rete testis must also
      be considered in atrophic testes. Here we review the papers published on this
      subject and report our recent cases.

PMID- 12792887
TI  - Sunburn reaction in the dorsal skin of hypotrichotic WBN/ILA-Ht rats.
AB  - The dorsal skin responses to a single irradiation with a high-dose of UVB
      (10kJ/m2) were examined histologically and immunohistochemically in UVB-sensitive
      Wistar-derived hypotrichotic WBN/ILA-Ht rats (HtRs). Sunburn cells (SBCs) which
      were characterized by pyknotic nuclei and eosinophilic cytoplasm and had
      ultrastructual characteristics of apoptotic cells were first observed in the
      epidermis at 3 hours (h) after irradiation. The number peaked at 6 h, and then
      decreased rapidly. The expressions of p53 protein, which is known to be closely
      related to the formation of SBCs, and of p21 protein, which is one of the
      transcriptional target genes of p53, were immunohistochemically detected, and
      their labeling index (LI) in the epidermis peaked at 12 to 24 h (p53) or at 24h
      (p21) after irradiation. On the other hand, proliferating cell nuclear antigen
      (PCNA)-LI in keratinocytes was significantly lower than the control group at 6 h
      after irradiation and thereafter it increased and became significantly higher
      than the control group from 24 to 48 h. At 48 h, moderate hyperplasia with
      moderate numbers of mitotic keratinocytes was first observed in the epidermis. In
      the dermis, mild edema developed from 12 to 36 h and it accompanied mild
      lymphocyte infiltration at 36 h. Judging from the present results, it was
      suggested that some factors other than p53 might be involved in SBC formation,
      and that p53 might induce p21 protein and play an important role in cell growth
      arrest in keratinocytes after UVB irradiation.

PMID- 12792888
TI  - Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian
      tumors of low malignant potential and adenocarcinomas.
AB  - OBJECTIVE: In view of the controversial information on the significance of the
      cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a
      retrospective investigation to clarify the relationships of this protein to
      proliferation rate, clinicopathological variables and prognosis of epithelial
      ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low
      malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained
      immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of
      cell proliferation). RESULTS: p21Cip1 levels were significantly higher in LMP
      tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those
      associated with minimal residual disease (p=0.008). However, no relationship
      existed between p21Cip1 expression and the proliferation rate of adenocarcinomas
      or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not
      accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype
      prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as
      well as in those left with minimal residual disease (p=0.059). In patients with
      lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related
      to poor overall survival on its own (p=0.0500) and when combined with p53 protein
      overexpression (p=0.0323). In multivariate analysis, only the stage remained as
      the independent predictor of survival. CONCLUSIONS: Decreased p21Cip1 expression
      is related to several indicators of aggressiveness in ovarian adenocarcinomas and
      seems to be differentially regulated in LMP tumors and adenocarcinomas. On the
      contrary, deregulation of p21Cip1 expression does not seem to participate in the
      pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with
      p53 is of prognostic significance in lower grade adenocarcinomas, it does not
      appear to add to the information gained from traditional prognosticators.

PMID- 12792890
TI  - In vivo cellular uptake of bismuth ions from shotgun pellets.
AB  - Shotgun pellets containing bismuth (Bi) are widely used and may cause a rather
      intense exposure of some wild animals to Bi. A Bi shotgun pellet was implanted
      intramuscularly in the triceps surae muscle of 18 adult male Wistar rats. Another
      group of 9 animals had a Bi shotgun pellet implanted intracranially in the
      neocortex. Eight weeks to 12 months later the release of Bi ions was analysed by
      autometallography (AMG) of tissue sections from different organs (brain, spinal
      cord, kidney, liver, testes). In the group with intramuscular Bi shotgun pellets
      no AMG staining could be found for the first 2-4 months; 6 months after exposure
      Bi was traced in the kidney. Twelve months after the implantation the kidneys
      were heavily loaded and Bi was also traced in testosterone-producing Leydig
      cells, in glial cells and in neurons of brain and spinal cord. In the central
      nervous system (CNS) motor neurons were the most loaded. In rats with
      intracranially implanted shotgun pellets a massive uptake of Bi was observed
      involving both glia and neurons throughout the brain. The cells close to the
      shotgun pellet had the highest uptake. The animals showed a pronounced Bi uptake
      in the ependyma cells lining the ventricular system and in the cubic epithelia
      covering the choroid plexus. Dissemination of Bi ions to the rest of the body was
      demonstrated by AMG tracing of Bi accumulations in the tubular cells of the
      kidney. These findings emphasize that metallic Bi, including shotgun pellets,
      represents sites of intense Bi pollution if implanted or shot into a living
      organism, and further that such metallic Bi bodies, if they enter the CNS, cause
      a spread of Bi ions throughout it.

PMID- 12792889
TI  - Combined analysis of tumor growth pattern and expression of endogenous lectins as
      a prognostic tool in primary testicular cancer and its lung metastases.
AB  - The aim of this study was to glyco- and immunohistochemically analyze expression
      of distinct growth/adhesion-related markers of primary testicular carcinomas and
      their lung metastases in relation to the risk of developing lung metastases and
      survival of patients, and to correlate immunohistochemical staining profile and
      syntactic structure analysis in order to delineate new prognostic parameters for
      this tumor type. Clinical features of 50 patients with primary testicular
      carcinomas and their corresponding lung metastases were evaluated and compared to
      those of a control cohort of 25 cases. The set of eight probes including labeled
      galectins-1 and -3, specific non-cross-reactive antibodies against galectins-1, 
      3, and -8 as well as anti-Ki-67, anti-bcl-2, and anti-p53 was applied to formalin
      fixed, paraffin-embedded tumor sections of both primary and metastatic lesions.
      Syntactic structure analysis computed staining intensities and structural
      features of the tumor cells. These parameters were set into relation separately
      and in combination to clinical data including tumor stages, smoking habits,
      applied cytostatic therapy, disease-free interval, and survival. The risk of
      testis cancer patients to develop lung metastases depends in descending order on
      the tumor cell type (non-seminoma versus seminoma), tumor cell heterogeneity
      (mixed versus monomorphous cell type), age of patients, and pT stage. The extent
      of differential expression of galectin-related features between primary and
      secondary lesions was pronounced. Prognostic correlations for distinct galectin
      related features were delineated in combination with data from syntactic
      structure analysis, for example cluster radius of galectin-3-positive tumor cells
      and post-surgical and total survival. Lengths of disease-free interval and total
      survival of patients were also correlated to characteristics obtained by
      syntactic structure analysis and their combination with galectin data in the
      first place, then to smoking habits, percentage of proliferating cells in the
      primary and secondary tumors, and finally to expression of certain galectins and
      of p53. Patients with non-seminoma testicular cancer should be thoroughly
      controlled for lung metastases. Regarding marker selection, our study underscores
      that further investigation of the growth-regulatory network of galectins is
      clearly warranted.

PMID- 12792891
TI  - Lectin binding patterns in normal canine endometrium and in bitches with pyometra
      and cystic endometrial hyperplasia.
AB  - Cystic endometrial hyperplasia (CEH) and pyometra in the bitch are dioestral
      syndromes, supposed to be caused by hormonal disturbances and changes in
      endometrial steroid hormone receptor levels. Histologically, the endometria show
      cystic dilated glands and, if bacteria succeed in invading the uterus, pyometra
      may develop in the following metoestrus. In this study, lectin histochemistry was
      performed on paraffin sections to compare carbohydrate expression of uterine
      glands and surface epithelium in healthy dogs and in dogs with CEH and pyometra.
      Lectin binding is a useful tool to identify glycoconjugates, especially of the
      glycocalyx, which has essential functions in the endometrium during reproduction.
      Uterine tissue was obtained from 18 healthy bitches in metoestrus or anoestrus
      and 18 bitches with a clinical diagnosis of CEH or pyometra. Normal endometria
      showed cycle-dependent changes in SBA, PNA, HPA and UEA binding during metoestrus
      and anoestrus. LCA did not show cycle-dependent changes and WGA bound to Golgi
      regions in the apical parts of surface epithelial cells only in metoestrous.
      Endometria with inflammatory alterations lost cycle-specific lectin binding
      patterns and, with increasing severity of pathological changes, showed a marked
      decrease in binding intensity to the glandular and surface epithelial glycocalyx
      and secretions. In dogs with CEH, unaltered glands with generally strong lectin
      binding to the glycocoalyx and Golgi regions were found adjacent to altered
      glands. The decrease of lectin binding in pyometra cases is supposed to be a
      result of glandular exhaustion after cystic hyperplasia. In addition, bacterial
      adhesion to sugar residues on the uterine surface epithelium might impede lectin
      binding.

PMID- 12792892
TI  - Upregulation of vascular endothelial growth factor (VEGF) in the retinas of
      transgenic mice overexpressing interleukin-1beta (IL-1beta) in the lens and mice
      undergoing retinal degeneration.
AB  - IL-1beta is a pro-inflammatory agent associated with angiogenesis and increased
      vascular permeability. To determine whether IL-1beta elicits these responses
      through an upregulation of VEGF, transgenic mice that overexpress IL-1beta in the
      lens were evaluated at various time points for the localization of VEGF, the
      location and extent of blood-retinal barrier (BRB) breakdown, and the origin and
      extent of neovascularization (NV). In homozygous and heterozygous transgenic
      mice, but not controls, intense VEGF immunoreactivity was scattered throughout
      the retina at postnatal days 5-7 (P5-7), just after the onset of inflammatory
      cell infiltration. VEGF staining in the retina remained widespread, but weak from
      P9-15. Beginning at P15, the intensity of VEGF immunoreactivity achieved a second
      peak, which it maintained through adulthood. This peak coincided with significant
      retinal destruction due to massive inflammation. The onset of BRB breakdown
      coincided with the upregulation of VEGF (P5-7) and widespread BRB breakdown was
      demonstrated from about P9. From P9-12, aggregates of cells positive for
      Griffonia simplicifolia isolectin-B4, a marker for vascular endothelial cells,
      formed on the retinal surface. These cells migrated into the retina at P12-15
      with the more superficial cells forming a network of vessels and the deeper cells
      remaining in small clusters, thus demonstrating that NV occurs much later than
      BRB breakdown. Non-transgenic FVB/N mice, which undergo retinal degeneration
      beginning at about P9, also demonstrate the latter peak of VEGF upregulation and
      the accompanying BRB breakdown, but not the early upregulation. VEGF
      immunostaining of transgenic and non-transgenic mouse retinas was eliminated by
      pre-incubation of the VEGF antibodies with VEGF peptide. The data suggest that
      the early peak of VEGF upregulation (P5-7) and its accompanying BRB breakdown is
      due to IL-1beta expression and is likely to be dependent on inflammatory cell
      infiltration. The latter peak appears to be related to retinal destruction.

PMID- 12792894
TI  - Localization of integrin alpha(v)beta3 and vascular endothelial growth factor
      receptor-2 (KDR/Flk-1) in cutaneous and oral melanomas of dog.
AB  - Melanomas are common neoplasms of dogs and arise from pigment-producing cells
      called melanocytes or melanoblasts. Melanomas of skin are often easily cured by
      surgical excision, but those of oral mucosa are aggressive, metastasize to the
      regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor
      growth is sustained by proliferation of microvessels via a process called
      angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in
      quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial
      growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via
      VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to
      investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and
      fresh samples from cases of canine melanomas. Results show that integrin
      alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas,
      respectively, and the expression was restricted to and immediately around the
      melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma
      revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual
      immuno-gold electron microscopy confirmed co-localization of integrin
      alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data
      demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2
      in cutaneous and oral melanomas of dogs.

PMID- 12792893
TI  - An electron microscopic and biochemical study of the effects of propranolol on
      the glycogen autophagy in newborn rat hepatocytes.
AB  - The effects of propranolol on the glycogen autophagy in newborn rat hepatocytes
      were studied by using biochemical determinations, electron microscopy and
      morphometric analysis. Propranolol lowered the liver cyclic AMP and cyclic AMP
      dependent protein kinase activity. It also decreased the formyl-methionyl-leucyl
      phenylalanine (FMLP)-inhibitable Ca2+-ATPase activity including lysosomal calcium
      uptake pump. The normal postnatal increase in the volume of autophagic vacuoles
      and the activity of acid glycogen-hydrolyzing alpha glucosidase were inhibited.
      Also, the degradation of glycogen inside the autophagic vacuoles was apparently
      inhibited. The activity of acid mannose 6-phosphatase was increased. These
      findings indicate that propranolol influences several steps in the sequence of
      events leading to the breakdown of glycogen in the autophagic vacuoles of newborn
      rat hepatocytes. This supports our previous studies suggesting that cyclic AMP
      regulates glycogen autophagy.

PMID- 12792895
TI  - Cell populations in the pineal gland of the viscacha (Lagostomus maximus).
      Seasonal variations.
AB  - Pineal samples of the viscacha, which were taken in winter and in summer, were
      analysed using both light and electron microscopy. The differences found between
      the two seasons were few in number but significant. The parenchyma showed two
      main cell populations. Type I cells occupied the largest volume of the pineal and
      showed the characteristics of typical pinealocytes. Many processes, some of which
      were filled with vesicles, could be seen in intimate contact with the
      neighbouring cells. The presence in the winter samples of "synaptic" ribbons and
      spherules, which were almost absent in the summer pineals, suggests a seasonal
      rhythm. These synaptic-like structures, as well as the abundant subsurface
      cisterns present in type I cells, appeared as basic differential features which
      allowed these cells to be distinguished from type II cells. These latter cells,
      which can be classified as interstitial cells, showed some other distinguishing
      features, such as irregular-shaped nuclei, abundant deposits of glycogen-like
      particles and structures of unknown function consisting of concentric cisterns
      surrounding a dense body. In the summer, interstitial cells displayed numerous
      large round bodies, which contributed to increase the cellular volume slightly.
      Regarding other constituents, like glial cell processes, vessels of non
      fenestrated endothelium and sympathetic innervation, no qualitative differences
      were observed between the two seasons studied. We have presented here some
      morphological evidences of the circannual rhythm of the viscacha pineal, as well
      as ultrastructural criteria for distinguishing the main cell populations of this
      organ, which could be useful for studies carried out in other mammals.

PMID- 12792896
TI  - Alterations induced on cytoskeleton by Escherichia coli endotoxin in different
      types of rat liver cell cultures.
AB  - Endotoxins (lipopolysaccharide, LPS) from Gram-negative bacteria are considered
      as the agents responsible for the induction of endotoxic shock, producing severe
      cellular metabolic dishomeostasis. Cytotoxic lesions, as well as functional and
      metabolic disturbances, occur mainly in the liver, which is one of the target
      organs and exerts an LPS clearance function. In an attempt to approach the
      molecular basis of endotoxic shock, and to propose an experimental model, we have
      focused this study on cytoskeleton (microtubules and microfilaments) alterations
      induced by different doses of endotoxin in different target liver cells.
      Microfilaments and microtubules were studied by immunofluorescence and different
      microscopy techniques (optic fluorescence microscopy and confocal laser scanning
      microscopy) in order to improve the cytoskeleton study resolution. Parenchymal
      and sinusoidal cell morphology, severely damaged by the LPS action, is related to
      a disturbance on the cytoskeletal organisation, even more evident in a particular
      proliferating rat liver cell culture. The most relevant changes are seen in the
      microtubule patterns in all liver cells tested, which could be related, depending
      on cell type, either to a direct LPS action or to [Ca+2]i dishomeostasis as well
      as free radical and cytokine (IL-1beta and TNF-alpha) production. Due to their
      features, proliferating rat liver cell cultures are used as a sensitive cell
      model to understand the effect of LPS on cytoskeleton organisation.

PMID- 12792897
TI  - Characterization and mRNA expression in an unusual odontogenic lesion in a
      patient with tricho-dento-osseous syndrome.
AB  - Odontogenic lesions are rare, but can be associated with significant morbidity.
      While their molecular determinants are unknown, they likely express many genes
      common to normal odontogenesis. This study evaluated the histology and mRNA
      expression of an unusual odontogenic lesion in a patient with a confirmed history
      of tricho-dento-osseous syndrome. METHODS: Decalcified, frozen 8 micro m sections
      of the lesion were cut and mounted on glass slides and stained with
      hematoxylin/eosin for analysis. The expression of multiple genes associated with
      normal odontogenesis and related pathologies were evaluated by RT-PCR, where
      possible in samples of the hard and soft tissue components of the lesion.
      RESULTS: Histological examination showed the lesion had large areas of irregular,
      dentine-like material, enamel matrix, areas of woven immature bone and multiple
      fully mineralised tooth crowns. Although most of the gene transcripts were
      amplified from both samples, some, including DLX3/7 and Collagen I demonstrated
      differential expression. CONCLUSIONS: This study shows the gene expression
      profile of aberrant odontogenesis with associated odontoma formation is similar
      to that of normal tooth and the genes expressed in other odontogenic lesions.
      While the role of altered gene expression in the development of such lesions has
      previously been postulated from transgenic models, this is the only report of an
      odontogenic lesion in a patient with TDO, and begins to elucidate possible gene
      interactions key to its development.

PMID- 12792898
TI  - Selective calcification of rat brain lesions caused by systemic administration of
      kainic acid.
AB  - Dystrophic calcification of previously damaged areas of nervous tissue occurs in
      a wide range of human diseases. The relationship between astroglial and
      microglial reactions and deposits of calcium salts was studied for up to five
      months in rats with a brain lesion produced by systemic administration of
      kainate. The morphology and atomic composition of the calcium salt deposits was
      also studied. Two types of lesions, sclerotic and liquefactive, were observed. In
      sclerotic lesions hyperplasia and hypertrophy of astrocytes partially substituted
      for the lost neurons, reaching a maximum in about twenty-five days after
      treatment. In liquefactive lesions, the astrocytic reaction occurred only around
      the liquefactive area. Microglial reaction was similar in both types of lesion
      and reached its highest expression in about twenty-five days. Calcium deposits
      were observed in the sclerotic but not in the liquefactive lesions. Clearly
      distinguishable granules of calcium salts were observed in sclerotic lesions
      under scanning electron microscopy after only five days post-injection. The size
      of calcified granules increased with time reaching 40 micro m or more in diameter
      at five months. The atomic composition of these deposits, studied by X-ray
      microanalysis, showed a time-dependent increase in calcium concentration. While
      there was no clear relationship between astroglial and microglial reactions and
      calcium salt deposits, the systemic injection of kainate produced progressively
      larger and more concentrated calcium deposits in sclerotic, but not in
      liquefactive lesions.

PMID- 12792899
TI  - Histochemical and chronological analysis of mouse submandibular gland parenchyma
      subjected to abrupt reperfusion.
AB  - We examined the effects of abrupt reperfusion on the mouse submandibular gland
      parenchyma and determined the degree of recovery from tissue damage. A main
      trophic artery supplying the gland was ligated with silk thread, and the ligature
      was then released after a variable period. The gland was removed at various times
      after reperfusion and then examined immunohistochemically and ultrastructurally.
      With reperfusion after 15 or 30 min of ligation, the tissue damage to the glands
      was slight or inapparent. With reperfusion after 1 or 3 h of ligation, collapse
      of the acini and the ducts was observed in parts of the lobules, but restoration
      of the parenchymal structures occurred, with the appearance of PCNA-positive
      cells, although there were differences in the level of restoration. After 6 h of
      ligation, most of the normal parenchymal cells had disappeared by the 5th and 7th
      days after reperfusion, and apoptosis and necrosis were present. These findings
      suggest that if interruption of the blood supply to the submandibular gland
      parenchyma is limited to within a few hours, then tissue repair after reperfusion
      is possible, although this will differ according to the level of damage, because
      the acini and the ducts reappear, probably with proliferation of parenchymal
      cells.

PMID- 12792900
TI  - Understanding the role of the cytoskeleton in the complex regulation of the
      endothelial repair.
AB  - Actin microfilaments and microtubules are important cytoskeletal proteins that
      regulate endothelial repair through alterations in cell shape and through
      regulation of cell migration following wounding of the endothelium. Upstream
      pathways have been identified in the regulation of actin and microtubule
      organization, especially small GTPases. Recently, there have been numerous
      proteins suggested to be capable of regulating interaction between microtubules
      and microfilaments to mediate microtubule regulation of endothelial repair, an
      important process in limiting injury to the artery wall and in reducing the
      extent of arterial disease. If disrupted, a rapid repair mechanism is important
      in reestablishing the integrity of the endothelium in order to reestablish its
      function as a macromolecular barrier, a thromboresistant surface, and a
      biologically active tissue. Strategies to improve repair should alter the
      pathobiology of the atherosclerotic plaque and thus improve the prognosis of
      patients with atherosclerosis.

PMID- 12792901
TI  - T cell regulation of the immune response to infection in periodontal diseases.
AB  - Although T cells have been implicated in the pathogenesis and are considered to
      be central both in progression and control of the chronic inflammatory
      periodontal diseases, the precise contribution of T cells to the regulation of
      tissue destruction has not been fully elucidated. Current dogma suggests that
      immunity to infection is controlled by distinct T helper 1 (Th1) and T helper 2
      (Th2) subsets of T cells classified on the basis of their cytokine profile.
      Further, a subset of T cells with immunosuppressive function and cytokine profile
      distinct from Th1 or Th2 has been described and designated as regulatory T cells.
      Although these regulatory T cells have been considered to maintain self-tolerance
      resulting in the suppression of auto-immune responses, recent data suggest that
      these cells may also play a role in preventing infection-induced immunopathology.
      In this review, the role of functional and regulatory T cells in chronic
      inflammatory periodontal diseases will be summarized. This should not only
      provide an insight into the relationship between the immune response to
      periodontopathic bacteria and disease but should also highlight areas of
      development for potentially new therapeutic modalities.

PMID- 12792902
TI  - Chromosomal instability and human hepatocarcinogenesis.
AB  - Recently, many studies have identified losses and gains of several chromosomal
      loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis
      and comparative genomic hybridization. Although distribution of aberrant
      chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q
      and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and
      loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related
      HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor
      progression, and some chromosomal aberrations, such as loss of 1p, are frequently
      identified in well-differentiated HCCs and also detected even in dysplastic
      nodule and cirrhotic nodule. This evidence suggests that chromosomal instability
      (CIN) emerges at an early stage during hepatocarcinogenesis and is successively
      inherent to tumor cells, resulting in acquisition of malignant phenotype. The
      molecular basis of CIN is beginning to be explored; however, several mechanisms
      may be involved for CIN of HCC.

PMID- 12792903
TI  - Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid
      tumours.
AB  - Interleukin-7 (IL-7) plays an important role in the normal development and
      maintenance of the human immune system. Its effects are mediated via its
      receptor, IL-7R. Ligand-receptor engagement results in a cascade of
      phosphorylation events mediated by various molecules including the Janus kinases
      (Jak1 and Jak3), PI3-kinase, Stats (signal transducers and activators of
      transcription) and other molecules. The activation of IL-7 signalling pathway
      results in survival, proliferation, differentiation and maturation of
      haematopoietic cells including B and T lymphocytes. Although the relationship of
      IL-7 with the development and differentiation of some haematological cancers like
      leukaemias and lymphomas is well recognised, little is known about it involvement
      with solid tumours. There are several studies that have revealed IL-7/IL-7R
      expression in epithelial systems and some human solid epithelial tumours.
      Furthermore, IL-7 can be produced by some human tumour cells and involved in
      tumour development and progression. In this review article we have summarised the
      main biological activities of IL-7 and its downstream signalling complex in
      relation to some human solid malignancies.

PMID- 12792904
TI  - The pathobiologic spectrum of Schwannomas.
AB  - In terms of their morphology, clinical associations and behavior, peripheral
      nerve sheath tumors are among the most varied of human neoplasm. Not
      surprisingly, such tumors are subject to frequent misdiagnosis. This is
      particularly true of the spectrum of schwannomas which include: a) conventional
      schwannoma, a histologically benign tumor which, on occasion, is destructive of
      surrounding osseous structures, b) the relatively recently described cellular
      schwannoma, a tumor that histologically simulates malignant peripheral nerve
      sheath tumor (MPNST), c) plexiform schwannoma which, particularly in cellular
      form and when occurring in childhood, simulates MPNST, and d) melanotic
      schwannoma which is often mistaken for melanoma. The psammomatous form of the
      latter is often associated with Carney complex, a rare heritable disorder that:
      a) includes cutaneous lentigines, b) myxomas of skin, subcutaneous tissue, and
      heart, c) and endocrine neoplasms. The tendency to misdiagnose schwannomas and to
      overestimate their grade makes schwannomas worthy of note. Herein, we discuss the
      four major schwannoma variants, their essential clinicopathologic features, and
      differential diagnosis. The distinction from MPNST is given particular attention.

PMID- 12792906
TI  - RNA is closely associated with human mast cell lipid bodies.
AB  - Both novel and multiple ultrastructural studies based on different principles
      show relationships of cytoplasmic lipid bodies and ribonucleic acid (RNA) of
      potential importance to RNA metabolism in human mast cells. The methods include
      general ultrastructural morphological observations, imaging of RNA with an EDTA
      regressive stain, imaging of the incorporation of radio labeled uridine by
      ultrastructural autoradiography, postembedding immunogold labeling of uridine,
      ribosomes and small nuclear ribonuclear proteins and ultrastructural in situ
      hybridization detection of poly(A)-positive messenger RNA. Altogether these
      studies implicate human mast cell lipid bodies in RNA metabolism and are
      analogous to earlier similar studies which showed that human mast cell granules
      also curtain RNA.

PMID- 12792905
TI  - Review of renal oncocytoma with focus on clinical and pathobiological aspects.
AB  - Renal oncocytomas account for about 3-7% of all renal tumors. Macroscopically,
      the cut surface of the tumor is generally mahogany brown or dark red in color. A
      central scar is occasionally observed. Histologically, tumor cells with finely
      granular cytoplasm proliferate in an edematous, myxomatous or hyalinized stroma
      with a nested, tubulocystic, solid or trabecular pattern. Ultrastructurally,
      tumor cells contain many mitochondria with lamellar cristae. Mitochondrial DNA
      alterations are consistently observed in renal oncocytomas. In chromosomal
      analysis, renal oncocytomas comprise a heterogenous group. Combined loss of
      chromosomes Y and 1, rearrangements affecting band 11q12-13, involvement of 12q12
      13, loss of 14q, and the lack of combination of LOH at specific chromosomal sites
      have been reported. In differential diagnosis, the histological separation from
      chromophobe RCCs is of great importance. In such a setting, ultrastructural or
      chromosomal analysis is very useful. However, there are several findings
      suggesting a close relationship between chromophobe RCC and oncocytoma. First,
      both tumors share a phenotype of intercalated cells of the collecting duct system
      and mitochondrial DNA alterations. Second, some cases of coexistent oncocytoma
      and chromophobe RCC, designated as "renal oncocytosis", have recently been
      reported. Third, oncocytic variants of chromophobe RCCs that have similar
      ultrastructural features to those of oncocytomas have been reported. Fourth, the
      existence of chromophobe adenoma, which is the benign counterpart of chromophobe
      RCC and shows loss of chromosomes Y and 1, has recently been suggested. Finally,
      although almost all oncocytomas behave in a benign fashion, some cases of
      oncocytoma that caused metastasis or resulted in death have also been reported.
      Therefore, further studies are needed to resolve these problems and also to
      elucidate the genetic mechanisms responsible for the occurrence of oncocytomas.

PMID- 12792907
TI  - Gene products involved in metastasis of bladder cancer.
AB  - Metastasis is usually responsible for mortality in patients suffering from muscle
      invasive bladder cancer. Whilst expression of a great number of genes and their
      protein products have been associated with metastasis and/or poor prognosis in
      bladder cancer, evidence that they actively drive the metastatic process, and
      hence make potentially good therapeutic targets, is often lacking. This is due to
      the limited number and application of effective animal models which reflect the
      pathogenesis of the human disease. In this review I will discuss the processes
      involved in metastasis, consider the established animal models of bladder cancer
      progression and metastasis, and review the evidence for a role of various gene
      products in this process. Consideration of clinical studies in conjunction with
      evidence from experimental animal models reveals that the tyrosine kinase
      receptor erbB1/EGFR, the calcium binding protein S100A4 and the the cell cycle
      arrest/apoptosis-inducing p53 protein are amongst the most promising targets for
      therapy against metastatic disease in patients with bladder cancer.

PMID- 12792908
TI  - Basigin (CD147): a multifunctional transmembrane protein involved in
      reproduction, neural function, inflammation and tumor invasion.
AB  - Basigin (Bsg) is a transmembrane glycoprotein with two immunoglobulin-like
      domains, and forms a family with embigin and neuroplastin. In these proteins a
      conserved glutamic acid is present in the middle for the transmembrane domain.
      Bsg is also called CD147 and EMMPRIN, and the symbol for the human basigin gene
      is BSG. BSG is located in chromosome 19 band p13. 3. Knockout mice deficient in
      the Bsg gene are sterile and show various neurological abnormalities. Bsg
      deficient embryos are also difficult to implant. Bsg has been found to
      participate in the cell-surface orientation of monocarboxylic acid transporters
      (MCTs) to the plasma membrane. Dysfunction of the retina in Bsg-deficient mice is
      ascribed to the failure of plasma membrane integration of MCTs in the tissue. Bsg
      is also involved in inflammatory processes and is proposed to be a receptor of
      cyclophilin A; it is also likely to participate in HIV infection. Bsg in tumor
      cells triggers the production or release of matrix metalloproteinases in the
      surrounding mesenchymal cells and tumor cells, thereby contributing to tumor
      invasion. Furthermore, the association of Bsg with integrins might be important
      in signaling through Bsg.

PMID- 12792909
TI  - Lipid kinases play crucial and multiple roles in membrane trafficking and
      signaling.
AB  - Phosphotidylinositols (PIs) are known to play an essential role in membrane
      trafficking and signaling transduction. PIs serve multiple functions, such as
      recruitment of cytosolic proteins with PI phosphate (PIP) binding domains and
      modification of the physical properties of the membranes in which they reside. As
      substrates for phosphoinositide-specific lipases they function as a switch point
      in phosphoinositide metabolism. Recent work with epidermal growth factor receptor
      (EGFR) and colony stimulating factor-1 receptor (CSFR) has identified a possible
      connection between endocytosis of activated receptors and type-1
      phosphatidylinositol-4-phosphate-5-kinase. Furthermore, serine/tyrosine
      phosphorylation of phosphatidylinositol-4-phosphate-5-kinase seems to be
      essential for its activities. Indeed, one of the products of the
      phosphatidylinositol-4-phosphate-5-kinases, PIP2, has been shown to be involved
      in multiple steps of endocytosis, including the assembly of the clathrin coat,
      regulation of adaptor proteins, and production of endocytic vesicles via the
      regulation of dynamin. The discussion in this review focuses primarily on
      receptors with intrinsic enzymatic activity, specifically on receptor tyrosine
      kinases (RTKs). We will discuss their structure; mechanism of action and
      potential role in membrane trafficking and/or signaling through the regulation of
      phosphatidylinositol phosphate kinases.

PMID- 12792912
TI  - The education of professionals.

PMID- 12792913
TI  - Relationship between pathology curricular approaches and performance in the
      United States medical licensing examination (USMLE), step 1: a national cross
      sectional study.
AB  - A collaborative multi-institutional study was conducted to study the relationship
      between characteristics of pathology instruction and student performance in the
      United States Medical Licensing Examination (USMLE), Step 1. Detailed
      descriptions of pathology instruction, such as curriculum format, style of
      instruction, and design of instruction of various areas of pathology for the 1996
      1997 academic year were matched with Step 1 total scores and pathology subscores
      for 10,159 students from 88 schools who took the June 1997 examination.
      Hierarchical linear modeling was used for analysis while controlling for
      students' MCAT-bpv scores (Medical College Admission Test scores, average of
      biological and physical sciences and verbal reasoning). The Step 1 total scores
      correlate with Step 1 pathology subscores, and both correlate with students' MCAT
      bpv scores. The MCAT-bpv scores account for most of the variation in Step 1
      scores. Of all of the curricular variables analyzed, 2 possible factors that
      significantly influence the impact of MCAT-bpv scores on Step 1 scores are (1)
      multidisciplinary format of instruction and (2) discipline-based general
      pathology instruction in year 2. Overall, the multidisciplinary format reduced
      the impact of MCAT-bpv scores on both the Step 1 total score and the pathology
      subscore by 1 point per MCAT-bpv. Overall, the general pathology instruction in
      year-2 increased that impact on Step 1 total score by 1 point per MCAT-bpv. The
      slope became less steep with multidisciplinary format and more steep with year-2
      general pathology instruction. As a result, students with higher MCAT-bpv scores
      tend to benefit from year-2 general pathology instruction, whereas those with
      lower MCAT-bpv scores appear to benefit from a multidisciplinary format. These
      differences become more apparent as the MCAT-bpv scores move away from the mean
      in either direction, indicating that scores of most students are not affected by
      curricular variables. Overall, there is no significant difference in the school
      means of Step 1 total scores and pathology subscores of schools with different
      curricular approaches. This is most likely due to the finding that the students'
      MCAT-bpv scores, and not curricular variables, are the major predictors of Step 1
      scores, and all schools have a mix of students with various MCAT-bpv scores.

PMID- 12792914
TI  - Self-instructional "virtual pathology" laboratories using web-based technology
      enhance medical school teaching of pathology.
AB  - Second-year medical students have traditionally been taught pulmonary
      pathophysiology at the University of California-Los Angeles (UCLA) School of
      Medicine using lectures, discussion groups, and laboratory sessions. Since 1998,
      the laboratory sessions have been replaced by 4 interactive, self-instructional
      sessions using web-based technology and case-based instruction. This article
      addresses nature of transformation that occurred from within the course in
      response to the infusion of new technologies. The vast majority of the course
      content has been digitized and incorporated into the website of the
      Pathophysiology of Disease course. The teaching histological slides have been
      photographed digitally and organized into "cases" with clinical information,
      digital images and text, and audio descriptions. The students study the materials
      from these cases at their own pace in 2 "virtual pathology" laboratory, with a
      few instructors supervising the on-site sessions. The students discuss additional
      cases available on the website in 2 other laboratory sessions supervised by a
      pulmonologist and a pathologist. Marked improvement in student participation and
      satisfaction was seen with the use of web-based instruction. Attendance at
      laboratory sessions, where the students had previously been required to bring
      their own microscopes to study histological slides at their own pace, increased
      from approximately 30% to 40% of the class in previous years to almost 100%.
      Satisfaction surveys showed progressive improvement over the past 4 years, as
      various suggestions were implemented. The value of web-based instruction of
      pathology at the UCLA School of Medicine is discussed.

PMID- 12792915
TI  - Implementation of virtual microscope slides in the annual pathobiology of cancer
      workshop laboratory.
AB  - Virtual slides are digital facsimiles of glass microscope slides that, when
      viewed with a pan and zoom viewer, can emulate viewing a glass slide with a
      traditional microscope. Based on successful implementation of virtual slides in
      medical student histology and pathology courses at the University of Iowa, we
      developed a plan to evaluate the use of virtual slides in the American
      Association for Cancer Research's annual Pathobiology of Cancer Workshop. In this
      Workshop, nonphysician predoctoral students and postdoctoral fellows working in
      cancer research explore the morphological, clinical, and molecular aspects of
      human cancer. Over the course of a week, students examine approximately 100 glass
      slides in microscope laboratories, facilitated by senior cancer investigators.
      The goal of the present study was to evaluate virtual slides as a teaching
      modality in these laboratories, not as a replacement for traditional microscopy,
      but rather in terms of their utility in facilitating student learning as they
      examine glass slides with a traditional microscope. Evaluation by questionnaire
      indicated that virtual slides enhanced students' ability to grasp morphological
      features better than the traditional photomicrographs. The results of this
      implementation suggest that virtual slide technology may be successfully extended
      to other educational venues where traditional microscopy and photomicrographs are
      currently used.

PMID- 12792916
TI  - A mission-based reporting system applied to an academic pathology department.
AB  - We report how data from the University of California (UC) Davis mission-based
      reporting system (MBR) can be used to define contributions for each division
      within a Department of Pathology based on faculty rank and series, and to
      evaluate whether these contributions are in alignment with the missions of the
      department and the goals of the school's leadership. MBR summary reports were
      generated for each division within the Department of Pathology; these reports
      illustrated the average contribution for each faculty rank and series in each of
      the following missions: investigative/creative work (research), teaching,
      clinical service, and administrative/community service. All divisions contributed
      equally to the teaching mission, averaging approximately 1/3 of a faculty
      member's time. Research was the primary mission for faculty in both the Research
      and the Clinical Pathology divisions, whereas clinical service was the primary
      mission for Anatomic Pathology. Both Anatomic Pathology and Clinical Pathology
      also played a large role in the administration/community service mission. These
      roles were appropriate based on the division's distribution of faculty in each of
      the faculty series. The average contribution to both the research and
      administrative/community service missions were larger for the Department of
      Pathology than it was for the school as a whole. The Department of Pathology's
      average contribution to both the teaching and clinical service missions was less
      than the school's average. We conclude that MBR data creates unique profiles for
      divisions and the department and enables interdepartmental comparisons that would
      not be possible by other means. Within the context of our school, the present
      analysis illustrates that the Department of Pathology is fulfilling the
      expectations of the school's leadership. In a more general sense, these profiles
      allow appropriate monitoring of the workforce, funds flow analysis, allocation of
      resources, and strategic planning in an academic medical center.

PMID- 12792917
TI  - Evaluation of the interobserver reproducibility of Gleason grading of prostatic
      adenocarcinoma using tissue microarrays.
AB  - The Gleason system is the internationally recognized standard for grading
      prostate cancer, due mainly to its strong prognostic capability. However,
      interobserver reproducibility is variable in the community setting. Herein we
      present a novel approach to evaluating Gleason grading among pathologists using
      high-density tissue microarrays (TMAs). A CD-ROM containing 537 different TMA
      spot images of 0.6-mm diameter was sent to 10 genitourinary pathologists in
      France. The pathologists were expected to score each TMA spot based on their
      experience evaluating standard prostate biopsies, transurethral resections, and
      prostatectomy samples. There was no consensus meeting beforehand to agree on how
      the group would apply the Gleason grading system for this project. Percentage of
      agreement and kappa value were used to assess the level of agreement. A short
      questionnaire was sent to assess pathologists' opinion on this new approach to
      evaluating Gleason grading. An average of 311 images were analyzed (range, 104 to
      537; median, 256.5). Four of the pathologists evaluated all 537 images and
      assigned Gleason grades to 149 images with an overall kappa for interobserver
      agreement for the exact score between 0.31 and 0.52 and between 0.45 to 0.69 if 3
      Gleason categories (</=6, 7, and >7) were used. When 2 categories were considered
      (</=7 or >7), kappa ranged from 0.58 to 0.83. All pathologists analyzed 104
      images. Similar results were obtained with an agreement between 0.28 and 0.54 for
      the 3 Gleason categories. After finishing this test, 90% of genitourinary
      pathologists considered this approach useful for resident training and 90% for
      pathology teaching. We conclude that a Gleason score can be easily assigned to
      each TMA spot of a 0.6-mm-diameter prostate cancer sample. These data also
      indicated that using TMA spot images may be a good approach for teaching the
      Gleason grading system due to the small area of tissue.

PMID- 12792918
TI  - The pattern of CD10 expression in selected pathologic entities of the prostate
      gland.
AB  - There is increasing evidence that neuropeptides, including bombesin, may
      influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer.
      One of the molecules tightly involved in the regulation of neuropeptide activity
      is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The
      pattern of CD10 expression in hyperplastic and neoplastic conditions of the
      prostate gland has not been previously described. Immunohistochemical staining
      for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of
      paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy
      specimens. Normal and hyperplastic acini showed strong and distinct membrane
      (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory
      cells. In contrast, no intercellular membrane or cytoplasmic staining of
      secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2
      or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed
      CD10 expression in the secretory cells; those cases shared a distinct
      morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed
      consistent absence of intercellular membrane and cytoplasmic CD10 expression in
      the secretory cells, with preserved expression in basal cells. Interestingly, the
      basal cells in basal cell hyperplasia lacked CD10 expression, and no expression
      was noted in the secretory cells in all cases examined. Atrophic acini and those
      associated with acute and chronic inflammation retained CD10 expression. In
      conclusion, a consistent differential pattern of CD10 expression was seen in
      basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in
      the pathobiology of the prostate gland.

PMID- 12792919
TI  - Neural cell adhesion molecule is upregulated in nerves with prostate cancer
      invasion.
AB  - Currently postulated mechanisms of perineural invasion (PNI) include interaction
      between tumor cells and nerves. Neural cell adhesion molecule (N-CAM), one of the
      well-known members of the immunoglobulin super-family of adhesion molecules, was
      implicated in PNI and metastasis in various types of cancer. Tissue microarray
      technology was used to build 2 sets of tissue array (with versus without PNI)
      from 50 prostate cancers (PCa). The slides were stained immunohistochemically,
      and the results were evaluated semiquantitatively using a 0 to 3+ scoring system.
      N-CAM staining was observed in all nerves with variable intensity. N-CAM
      expression was upregulated in 73% (31 of 42) of the nerves with PNI compared with
      nerves without PNI (P >.001). The results suggested that N-CAM is probably
      involved in PNI in PCa. It is conceivable that cancer cells, through a yet-to-be
      established paracrine loop, signal the nerve to increase N-CAM production and
      increase adhesion. N-CAM upregulation in nerves may also facilitate cancer cells
      to migrate toward nerves and promote the process of perineural spread through
      increased survival using the nuclear factor kappa B pathway.

PMID- 12792920
TI  - Florid basal cell hyperplasia of the prostate: a histological, ultrastructural,
      and immunohistochemical analysis.
AB  - Basal cell proliferation is a common finding in a benign hyperplastic prostate
      gland. Occasionally, basal cell hyperplasia is so florid that it can be mistaken
      for prostatic adenocarcinoma. We characterized histological, ultrastructural, and
      immunohistochemical features of florid basal cell hyperplasia from transurethral
      resections (n = 11) and prostatectomy specimens (n = 4). Fifteen cases of
      prostatic adenocarcinoma were used as comparison. Intraluminal calcification was
      present in 40% of florid basal cell hyperplasia cases (6 of 15) and a unique
      finding of intracytoplasmic hyaline globules was detected in 53.3% of florid
      basal cell hyperplasia cases (8 of 15). Ultrastructural analysis revealed luminal
      calcification and intracytoplasmic electron-dense globules in foci of basal cell
      hyperplasia. Crystalloids, a frequent finding in low-grade prostate cancer, were
      absent in all 15 cases of florid basal cell hyperplasia. By immunohistochemistry,
      the basal cell-specific 34betaE12 and p63 as well as glutathione-s-transferase pi
      were positive in all basal cell hyperplasia cases but negative in all prostatic
      adenocarcinomas. These distinguishing features of florid basal cell hyperplasia
      are helpful in differential diagnosis from prostatic adenocarcinoma. Cytokeratins
      8 and 18 were both positive in basal cells, benign secretory cells, and carcinoma
      cells, failing to be of discrimatory value. Immunostaining for alpha-methylacyl
      coenzyme racemase, a new prostate cancer marker, was negative in hyperplastic
      basal cells but detected a distinct minor benign cell population in basal cell
      hyperplasia of possible neuroendocrine origin.

PMID- 12792921
TI  - Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor
      suppressor gene products, Ki-67, and sex steroid receptors in endometrial
      carcinoma: positive staining for cyclin A as a poor prognostic indicator.
AB  - Although aberrant expression of several cell-cycle regulators has been reported
      in endometrial carcinoma, correlations among these factors and their prognostic
      significance have not fully been elucidated. In the present study, expression of
      cyclins (D1, E, A, and B1), cyclin-dependent kinases (cdk2, cdk4, and cdc2), and
      tumor-suppressor gene products (p53, p21, and p27) were systematically examined
      by immunohistochemistry in 82 cases of endometrial carcinoma and 20 normal
      endometria. Results were compared with the expression of Ki-67, sex steroid
      receptor status, clinicopathological parameters, and patient outcomes. Positive
      staining for cyclin D1, cyclin E, cyclin A, cyclin B1, cdk2, cdk4, cdc2, p53,
      p21, and p27 was observed in 63%, 66%, 31%, 32%, 51%, 77%, 71%, 43%, 35%, and 60%
      of the 82 carcinomas, respectively. Among these factors, positive staining for
      cyclin D1, cdk4, and p53 was significantly frequent in advanced-stage tumors, and
      that for cyclin D1, cyclin A, cdk4, p21, and p53 was more frequent in higher
      grade tumors. High correlation was found between cyclin A and p53 expression,
      between cyclin D1 and cdk4 expression, between cdk4 and Ki-67 expression, and
      between p21 and Ki-67 expression. Multivariate analysis showed that the factors
      for poor prognosis were advanced stage and cyclin A positivity. These findings
      suggest that various cell-cycle regulators are involved in activated cell growth
      of endometrial carcinoma, and that positive staining for cyclin A could be a
      useful marker for unfavorable patient prognosis.

PMID- 12792922
TI  - Value of combined morphologic, cytochemical, and immunophenotypic features in
      predicting recurrent cytogenetic abnormalities in acute myeloid leukemia.
AB  - To evaluate the reliability of previously described morphologic, cytochemical and
      immunophenotypic criteria for the identification of acute myeloid leukemias
      (AMLs) with t(8;21), inv(16)/t(16;16) and t(15;17), 300 cases were reviewed
      retrospectively. Eighteen AMLs with features of t(8;21), 31 with features of
      inv(16)/t(16;16), and 22 with features of t(15;17) were identified. Cytogenetic
      studies were available for 228 cases and identified 15 cases of t(8;21), 30 cases
      of inv(16)/t(16;16), 18 cases of t(15;17) and 11 cases 11q23 AML. The true
      positive rate for pre-cytogenetic evaluation was 95% for t(15;17), 88% for
      inv(16)/t(16;16) and 87.5% for t(8;21). No difference in 5-year survival was
      identified in the precytogenetic and corresponding cytogenetic disease groups. No
      specific features to predict 11q23 abnormalities were identified. This study
      confirms the reliability of a combined morphologic, cytochemical and
      immunophenotypic approach to the initial classification of AML. Cytogenetic
      studies are still needed on all cases to identify the small proportion of cases
      that will be missed by these methods and to identify other significant
      cytogenetic abnormalities in AML.

PMID- 12792923
TI  - Clinicopathologic study of 43 patients with sural nerve vasculitis.
AB  - Vasculitis is a relatively uncommon finding in sural nerve biopsy specimens and
      is associated with significant morbidity. This study retrospectively reviewed the
      clinicopathologic features of 43 patients (44 sural nerve biopsy specimens) with
      sural nerve vasculitis, defined as infiltration of vessel walls by inflammatory
      cells. These biopsy specimens were obtained over a 19-year period, during which
      1503 nerve specimens were reviewed. The study group comprised 29 females and 14
      males, ranging in age from 19 to 94 years (mean, 72.5 years) at the time of
      biopsy. The most frequent clinical presentations included paresthesias in 19
      patients (61%), pain in 17 patients (57%), weakness in 10 patients (32%), and
      weight loss in 9 patients (29%). Histologically, 26 of 44 biopsy specimens (59%)
      demonstrated necrotizing vasculitis. The remaining 18 biopsy specimens
      demonstrated a nonnecrotizing lymphocytic vasculitis. Eosinophils were identified
      in 4 biopsy specimens, intravascular thrombi in 10 (22%) specimens, and
      granulomatous inflammation in 1 specimen. In 39 biopsy specimens (89%), multiple
      vessels were involved by vasculitis. Epineurial vessels were the most common
      target of vasculitis, (n = 42; 95%). Evidence of vascular wall scarring,
      indicative of healed vasculitis, was observed in 13 biopsy specimens (30%). All
      biopsy specimens showed evidence of axonopathy, with mild axonal loss noted in 14
      specimens (32%), moderate loss in 18 specimens (41%), and severe loss in 12
      specimens (27%). Concomitant muscle biopsy was performed in 31 patients. Fifteen
      muscle biopsy specimens demonstrated evidence of vasculitis (48%), which was
      necrotizing in 11 cases. All muscle biopsy specimens demonstrated features of
      neurogenic atrophy. Twenty-five out of 32 patients were known to have been
      treated with steroids and demonstrated some degree of clinical improvement. In
      conclusion, sural nerve vasculitis is a relatively uncommon pathological finding
      (prevalence of 2.9% in this study). In most cases, multiple vessels were
      involved. Concomitant vasculitis was also identified in about half of the muscle
      biopsy specimens obtained at the time of nerve biopsy. In most patients, the
      vasculitis appeared to be at least partially responsive to immunosuppressive
      therapy.

PMID- 12792924
TI  - The value of autopsy in pediatric cardiology and cardiovascular surgery.
AB  - Autopsy has been considered extremely helpful in determining the accuracy of the
      premorbid diagnosis. With recent advances in diagnostic imaging, the value of the
      autopsy has been called into question. The aim of this study was to assess the
      value of the pediatric autopsy in the current era of advanced diagnostic
      technology and sophisticated surgical intervention for congenital heart disease
      (CHD) and also to determine the autopsy's potential impact on clinical
      management. We compared the data from the postmortem examination of 29 children
      with CHD with the data obtained before death and evaluated for the accuracy of
      the diagnosis of the cardiac anatomy as well as the cause of death. The diagnosis
      of the anatomy was confirmed in 13 cases (45%), additional cardiovascular
      abnormalities with potential clinical impact were found in 11 cases (38%), and
      additional abnormalities without clinical impact were found in 5 cases (17%). The
      cause of death was confirmed in 15 cases (52%), determined by autopsy in 12 cases
      (41%), and uncertain in 2 cases (7%). We conclude that the pediatric autopsy
      continues to provide clinically relevant information with a potential impact on
      patient management and to reveal unexpected causes of death in a significant
      proportion of patients with CHD.

PMID- 12792925
TI  - Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens.
AB  - Although enteroviruses have long been considered the most common cause of
      inflammatory heart muscle diseases, parvovirus B19 (PVB19) is emerging as a new
      and important candidate for myocarditis and dilated cardiomyopathy with
      inflammation (DCMi) and without inflammation (DCM). We investigated left
      ventricular endomyocardial biopsy specimens from 110 patients with suspected
      inflammatory heart disease for the presence of PVB19, Coxsackie virus (CVB), and
      adenovirus (Ad2) genome by polymerase chain reaction. Diagnosis of myocarditis
      (36 patients), DCM (18 patients), DCMi (13 patients), and perimyocarditis (12
      patients) was made by immunohistochemical and histopathological investigation of
      endomyocardial biopsy specimens. A control group consisting of patients with
      arterial hypertension was also investigated. Prevalence of the PVB19 genome in
      endomyocardial biopsy specimens was highest in patients with DCMi (3 of 13) and
      patients with myocarditis (7 of 36); in patients with DCM and perimyocarditis,
      prevalence was 3 of 13 and 2 of 12, respectively. In patients with resolved
      myocarditis, no PVB19 DNA was detected; in patients with no inflammation and
      controls, prevalence was only 4% and 7%, respectively. CVB-RNA was detected in
      endomyocardial biopsy specimens from 3 of 37 patients with myocarditis; Ad2-DNA
      was found in 1 patient with DCM and 1 patient with perimyocarditis. These
      findings suggest an association of the PVB19 genome in endomyocardial biopsy
      specimens of adults with the development of DCM, DCMi, and chronic myocarditis
      more frequently than previously expected. PVB19 should therefore be recognized as
      a potential cardiotropic pathogen in patients of all ages.

PMID- 12792926
TI  - A hybrid form of myeloid/NK-cell acute leukemia and myeloid/NK-cell precursor
      acute leukemia.
AB  - Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined
      only in recent years. In the Revised European-American Lymphoma and World Health
      Organization classifications, only the mature NK-cell malignancies are included.
      However, at least 3 types of precursor NK-cell neoplasms have been reported in
      the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell
      precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias
      are characterized by the presence of blasts, which express CD56, in the
      peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report
      a case that is morphologically consistent with myeloid/NK-cell acute leukemia but
      immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique
      in its cutaneous presentation without involvement of the peripheral blood.
      Extensive flow cytometric studies were performed on the skin biopsy and bone
      marrow aspirate specimens, which included many markers that had not been tested
      before in these entities. The clinical implications of these findings are
      discussed.

PMID- 12792927
TI  - Pulmonary coinfection by Trichomonas vaginalis and Pneumocystis sp. as a novel
      manifestation of AIDS.
AB  - A 41-year-old man was hospitalized, presenting increasing dyspnea and extensive
      ground-glass opacities on chest X-ray. Infection by human immunodeficiency virus
      was confirmed. Cytologic examination of bronchoalveolar lavage fluid revealed
      numerous trichomonads and aggregates of Pneumocystis sp. Treatment was followed
      by rapid improvement of respiratory symptoms and chest X-ray. The trichomonad
      species found in the lungs was identified as Trichomonas vaginalis by small
      subunit rRNA gene amplification and sequencing. With the exception of rare cases
      of contamination of newborn babies during delivery, T. vaginalis has never been
      found in lungs in healthy or immunocompromised adults. In the present case, T.
      vaginalis is found as coinfecting agent. Our data, like those found in the
      literature, suggest that trichomonads are overlooked parasites that may be
      regularly implicated in diverse human pathologies.

PMID- 12792928
TI  - A single-institution review of the National Institutes of Health recommendation
      for prognostication of gastrointestinal stromal tumor.

PMID- 12792935
TI  - Toggling enantioselective catalysis--a promising paradigm in the development of
      more efficient and versatile enantioselective synthetic methodologies.
AB  - The increasingly needed synthesis of both enantiomers of a chiral compound
      usually requires the use of both enantiomers of a chiral catalyst. Several of the
      usually employed chiral ligands are naturally available in only one enantiomeric
      form, the antipode often being of labor-intensive preparation. Enantiodivergent
      asymmetric catalysis has accrued in importance in this regard, in that it allows
      expeditious access to both enantiomers of a product without any direct
      modification on the chemical structure of the chiral promoter. Various promising
      examples will be discussed throughout the review. If available or envisageable, a
      mechanistic rationale for the observed enantioinversion will be outlined.

PMID- 12792936
TI  - Chiral organometallic half-sandwich complexes with defined metal configuration.
AB  - Chiral organometallic half-sandwich complexes with stereogenic metal atoms are
      close relatives of chiral organic compounds with stereogenic carbon atoms.
      Similarities and differences between these two classes of compounds are outlined.
      Some representative metal complexes are discussed in an introductory section
      followed by a more detailed treatment of the available strategies to control the
      metal configuration by means of chiral auxiliaries. Special sections are devoted
      to the discussion of the configurational stability of chiral-at-metal complexes
      and their applications in stoichiometric and catalytic stereoselective reactions.

PMID- 12792937
TI  - Two-dimensional supramolecular self-assembly probed by scanning tunneling
      microscopy.
AB  - Supramolecular chemistry has a very large impact on chemistry of current interest
      and the use of non-covalent but directional forces is appealing for the
      construction of 'supramolecular architectures'. The invention of scanning probe
      microscopy techniques has opened new doorways to study these concepts on
      surfaces. This review deals with recent progress in the study of two-dimensional
      supramolecular self-assembly on surfaces probed by scanning tunneling microscopy,
      with a special emphasis on structure, dynamics and reactivity of hydrogen bonded
      systems.

PMID- 12792938
TI  - A recent development in computational chemistry: chemical reactions from first
      principles molecular dynamics simulations.
AB  - First-principles molecular dynamics simulations have recently been found an
      effective tool to study a large variety of chemical problems. Finite temperature
      simulations reveal unique information, including explicit dynamical effects and
      the evaluation of proper free energy differences. Moreover, dynamics simulations
      reveal information on the flexibility of molecular systems, and elucidate, often
      otherwise inaccessible, mechanistic details of chemical reactions. In addition
      this methodology allows the study of larger, periodic, systems, revealing
      computationally unique information which may be directly compared to experiments
      on realistic chemical systems. A variety of examples will be given, although most
      focus on the important field of catalysis.

PMID- 12792939
TI  - The stereospecific synthesis of P-chiral biophosphates and their analogues by the
      Stec reaction.
AB  - This manuscript summarizes the results of studies on the application of the
      reaction of dialkyl (aryl) phosphoramidate anions with carbonyl electrophiles for
      stereospecific synthesis of P-chiral biophosphates (Stec reaction). Following the
      results obtained with organic phosphoramidates which delineated the scope of the
      reaction and its stereochemical course, the application of the title reaction is
      presented for the preparation of diastereomerically pure P-chiral cyclic
      nucleotide analogues (phosphorothioates, phosphoroselenoates,
      phosphoroselenothioates, isotopomeric 18O-phosphates), and P-chiral nucleoside
      monophosphate analogues, as well as dinucleoside phosphate analogues
      (phosphorothioates, methanephosphonates).

PMID- 12792940
TI  - Recent applications of bifunctional trityl groups.
AB  - Triphenylmethyl derivatives represent an important class of dyestuffs as well as
      a useful family of protecting groups widely used in organic synthesis to
      transiently block various functional moieties. These applications are well
      documented and have been a subject of a number of reviews. Here we focus instead
      on some novel applications of a trityl which make good use of its ability to
      easily form a stabilised cation in combination with additional peripheral
      functionalities. Topics covered include applications in bioconjugation, cross
      linking, mass-spectrometry, fluorescence and optics.

PMID- 12792941
TI  - Going wireless: D.C. hospital gears up for the transition.

PMID- 12792942
TI  - Tips from the field.... How to prepare for HIPAA's arrival.

PMID- 12792943
TI  - Analyzing planned maintenance (PM) inspection data by failure mode and effect
      analysis methodology.
AB  - There is no question that medical devices are becoming more reliable. However, we
      have had some difficulty finding a satisfactory method for providing persuasive
      documentary evidence that this improved reliability will allow us to relax our
      traditional planned maintenance (PM) practices without compromising patient
      safety. The acceptance and increasing use of Failure Mode and Effect Analysis
      (FMEA) by several of the oversight agencies, including the Joint Commission on
      Accreditation of Healthcare Organizations, provides us with an important
      opportunity to take another shot at this vexing problem. Using this proven FMEA
      methodology and some relatively simple rules to quantify the results of the
      routine PM inspections that all healthcare providers are still performing in
      considerable abundance, we have developed a method that allows us to reduce the
      test results to a simple, single measure (the Risk Score) that can be used to
      characterize the effectiveness and levels of safety of our current PM regimens.
      When tested on theoretical data and a sample of real PM inspection results, the
      method provides answers that seem reasonable. Although it will probably require
      some modification as we begin the standardized data gathering and gain working
      experience, it is our hope that this new approach will become generally accepted
      within the industry. This kind of positive response should enable us to persuade
      the various accrediting and licensing agencies to similarly accept the concept.

PMID- 12792944
TI  - A new perspective on clinical technology management.
AB  - In 1996 Intermountain Health Care (IHC) launched an endeavor for the development
      of a strategy that would provide a systematic management of its assets,
      specifically, clinical equipment. The scope would be enterprise wide and would
      focus on the 6 diverse elements of the "Equipment Life Cycle." These elements
      include: planning, assessment, acquisition, utilization, maintenance, and
      disposition. This endeavor resulted in the deployment of Clinical Technology
      Management (CTM). This article addresses the development of the concepts and
      methods used to organize CTM in 1996 and the subsequent refinements for the past
      6 years and in its entirety, this article is a mere summary of thousands of hours
      of work for 6 years.

PMID- 12792945
TI  - Clinical thermometry: possible causes and potential solutions to electronic,
      digital thermometer inaccuracies.
AB  - Previous research has indicated that the improvements in safety, speed, and ease
      of use of the newer electronic, digital oral and tympanic clinical thermometers
      have been offset by a loss in accuracy and reliability when compared with the
      traditional glass/mercury oral clinical thermometers. The purpose of this study
      was to determine possible causes of the relative lack of accuracy and reliability
      in these thermometers and suggest logical potential solutions. Evidence has been
      reviewed, which suggests that problems with the tympanic thermometers are the
      result of the range of normal anatomical variability. The combination of an
      otoscope with the tympanic thermometers is suggested and discussed as a potential
      solution. Evidence has been reviewed, which suggests that problems with the newer
      oral thermometers are the results of the size of the temperature sensors and the
      speed with which they respond. The small sensor size results in variability in
      placement relative to the primary heat source. The speed of sensor response
      results in too great a sensitivity to local, acute vasomotor activity (clinical
      temperature noise). Potential solutions, including an increase in sensor size and
      a reduction in response speed are discussed.

PMID- 12792946
TI  - Location systems could offer greater precision, data.

PMID- 12792947
TI  - Implementing cost-effective ways to reduce endoscope repair expenses.

PMID- 12792948
TI  - Batteries: what causes them to fail?
AB  - Rechargeable batteries do not die suddenly but gradually get weaker over time.
      The ability to hold charge diminishes through aging, usage (cycling), handling
      and environmental conditions. Batteries seem to have their own inherited life
      span. A fixed replacement plan, in which all batteries are replaced at a certain
      age, does not work well. Rather, each battery should periodically be analyzed and
      only those replaced whose capacity drops below an acceptable performance
      threshold. Implementing such a maintenance program reduces unexpected downtime
      caused by weak batteries and saves money. Unexpected downtime due to failing
      batteries can cause tense moments for the equipment operator. Some people may
      even seek legal compensation for personal damages suffered by a failing battery.

PMID- 12792949
TI  - Improving your wireless security.

PMID- 12792950
TI  - Developing a culture of safety.

PMID- 12792951
TI  - Software testing--how much is enough?

PMID- 12792952
TI  - [Surgical treatment of giant aneurysms of ascending parts and arch of the aorta
      in condition of deep hypothermia and circulatory arrest with artificial assisted
      circulation].
AB  - Sternotomy in giant (10 cm and more in diameter) aneurysms is highly dangerous
      due to possibility of injury of aneurysmatic wall with fatal bleeding. That is
      why sternotomy in condition of artificial circulation (AC) and cooling of
      patients to 29-30 degrees C are preferred. Two cases of successful surgical
      treatment of critical patients with giant aneurysms of ascending parts and arch
      of the aorta in condition of femoro-femoral AC, hypothermia (20 degrees C) and
      circulatory arrest are presented. One of the patients had a giant false
      posttraumatic aneurysm of an ascending part of the thoracic aorta with fistula
      between aneurysm and pulmonary artery. Suturing of defects of ascending aorta and
      pulmonary artery wall, aneurysmorrhaphia of pulmonary artery were performed. The
      other patient with acute disruption of a giant dissected aortal aneurysm and
      hemomediastinum underwent prosthesis of ascending part and arch of the aorta.

PMID- 12792953
TI  - [Short and long-term results of surgical correction of the aortal valve
      dysplasia].
AB  - Nearest and long-term results of surgical treatment of 108 patients with
      dysplasia of aortal valve were analyzed. Necessity of individual approach to
      choice of method of surgical correction (prosthesis or valvuloplasty of aortal
      valve) depending on degree of dysplasia and/or secondary valvular pathology, it
      anatomic variants, presence of concomitant infectious endocarditis and age of
      patients is noted. This permitted to reduce hospital lethality from 8.8 to 3.9%.
      Survival in 1, 5 and 10 years after prosthesis and valvuloplasty of aortal valve
      was 92.3 +/- 3.3, 86.8 +/- 4.8 and 85.7 +/- 5.7% versus 100, 94.1 +/- 4.1, 94.1
      +/- 4.1% respectively. Quality life in remote period was evaluated as good in
      80.3% operated patients, as satisfactory--in 11.1% and unsatisfactory--in 8.6%.

PMID- 12792954
TI  - [Results of surgical treatment of lung cancer in patients over 70 years old].
AB  - Results of surgical treatment of 345 patients (210 men--61%; 135 women--39%) over
      70 years with non-small-cell lung cancer were analyzed. Central lung cancer was
      diagnosed in 141 (40.9%), peripheral--in 204 (59.1%) patients. Squamous cell
      cancer was seen in 233 (67.3%), glandular--in 67 (19.4%), dimorphic--in 22
      (6.5%), large-cell--in 23 (6.8%) patients. Stage I of the disease was diagnosed
      in 121 (35.1%); stage II--in 49 (14.1%); stage III--in 175 (50.8%) patients. Rate
      of postoperative complications in the study group was 27.8%, lethality--6.4%. The
      highest lethality was after combined pneumonectomy. The most frequent
      postoperative complications were pneumonia (7.5%), arrhythmia (10.1%), pulmonary
      heart insufficiency (4.9%). Five-year survival after radical surgery in patients
      over 70 years with lung cancer was 49%, in patients with stage I of the disease
      this parameter was the highest--71.4%.

PMID- 12792955
TI  - [Treatment of middle-lobe syndrome].
AB  - Results of treatment of 242 patients with middle-lobe syndrome are analyzed.
      Indications for surgical treatment of middle-lobe syndrome must be determined
      very individually. Organo-saving surgeries are the methods of choice for benign
      processes in the middle lobe. In malignant tumors, destructive and cirrhotic
      processes of the middle lobe the resections are indicated.

PMID- 12792956
TI  - [Surgical treatment of gastric and duodenal ulcer disease with chronic duodenal
      obstruction].
AB  - One hundred and twenty-nine surgeries were performed from 1990 to 2001 for
      gastric (50) or duodenal (79) ulcers with chronic duodenal obstruction. Resection
      of 1/2 of the stomach by Bilrot-I was performed in 118 patients, pylorus-saving
      resection with creation of areflux valve in duodenal bulb--in 5, selective
      proximal vagotomy with duodenoplasty--in 6 patients. In early postoperative
      period complications were seen in 10 (10.9%) patients, postoperative lethality
      was 0.8% (one patient died). There was no insufficiency of anastomotic sutures.
      Postoperative stay was 11.3 +/- 1.5 days. In remote period after surgery symptoms
      of chronic pancreatitis was in 2.3% patients, but there were no symptoms of
      duodenostasis. Roentgenological symptoms of compensated duodenal obstruction were
      seen in 2 patients operative on for decompensated duodenostasis. These patients
      had no complaints.

PMID- 12792957
TI  - [Immediate results of pancreatoduodenal resection with end-loop
      pancreatoenteroanastomosis].
AB  - Immediate results of 151 pancreatoduodenal resections (PDR) were analyzed. This
      surgery was performed for tumors of gastropancreatoduodenal region in 88.1%
      patients, for chronic complicated pancreatitis--in 11.9%. Pylorus-saving PDR was
      performed in 82.8% patients, in combination with stomach resection--in 17.2%.
      Extended and regional pancreatectomy was performed in 20.3% patients with tumors
      of periampullar zone, extended lymphadenectomy--in 44.4%.
      Pancreatoenteroanastomosis was created in 82.8% patients, end-loop
      Wirsungenteroanastomosis by original author's method--in 52.3% of them,
      traditional Wirsungenteroanastomosis end-to-side--in 30.5%, complete external
      drainage of pancreas stump was performed in 13.9%, suturing of pancreas stump--in
      2.6%, pancreatogastroanastomosis was created in 1 (0.7%) patient. There was no
      insufficiency of pancreatoduodenoanastomosis performed with original method,
      while in traditional Wirsungenteroanastomosis it was seen in 4.4% patients. End
      loop anastomosis permitted to reduce number of complications after PDR 1.6--3
      times. General lethality was 11.3%, in end-loop anastomosis--3.8% that
      significantly lower than after other methods of treatment of pancreas stump.

PMID- 12792958
TI  - [Changes of immune indices in pancreonecrosis and their correction].
AB  - Indices of immune status, lipid peroxidation and intoxication syndrome were
      assessed in 54 patients with acute destructive pancreatitis after surgery.
      Immunodeficiency developed in pyoseptic complications. Polyoxidonium was used in
      22 patients for correction of secondary immunodeficiency. This drug reduces
      number of septic complications, lethality and hospital day.

PMID- 12792960
TI  - [Traumatic surgeries on organs of gastrointestinal tract without components of
      donor's blood].
AB  - The authors propose a complex program aimed to refuse completely using donor's
      blood components in surgeries on organs of digestive tract. This method was used
      in 25 patients who underwent surgeries with 380-1500 ml of blood loss. No
      patients received transfusion of donor's blood components before, during and
      after surgery.

PMID- 12792959
TI  - [Choice of the policy, terms, and method of surgery in acute cholecystitis].
AB  - Results of treatment of 763 patients with different forms of cholecystitis were
      analyzed. It was revealed that complex ultrasonic examination with dopplerography
      identifies the form of acute cholecystitis, allows to, predict technical
      difficulties in cholecystectomy and define optimum method of surgery. Comparative
      assessment of time of surgeries, rate of conversion of surgical approach, number
      of intra- and postoperative complications, lethality demonstrated that early
      urgent surgeries in acute cholecystitis before formation of inflammatory
      paravesical infiltrate in patients without high anesthesiological risk were
      similar to ones in elective surgeries and surpassed results of delayed surgeries.
      Early urgent surgeries permit to decrease hospital stay of patients with acute
      cholecystitis and reduce cost of treatment.

PMID- 12792961
TI  - [Basic principles of introduction of laparoscopic surgery in outpatient clinic].
AB  - The authors performed 1389 laparoscopic surgeries in one-day hospital of
      outpatient clinic. The majority of surgeries were carried out for cholelithiasis
      and inguinal hernia. Conditions for laparoscopic surgeries in outpatient clinics,
      indications and contraindications for this procedures were developed. Combination
      of laparoscopic technologies with non-hospital forms of surgical care
      organization permitted to achieve medical, social and economic effects.

PMID- 12792962
TI  - [Prolonged postoperative analgesia in abdominal surgery].
AB  - One hundred and sixty-two patients operated on organs of lower part of abdominal
      cavity were studied. All the patients were divided into 3 groups depending on
      anesthesia method: general, epidural and spinal anesthesia. Efficacy of different
      methods of intrasurgical anesthesia for prevention of postoperative algetic
      syndrome and decrease of complications number was compared. It is demonstrated
      that spinal and epidural anesthesia ensure prophylaxis of postoperative algetic
      syndrome, but spinal anesthesia is the most simple, safe and cost-effective
      method.

PMID- 12792963
TI  - [Results of treatment of isolated and combined trauma of urogenital system].
AB  - Retrospective analysis of treatment results of 608 patients with trauma of organs
      of urogenital system (UGS) was carried out. Beating was the cause of trauma in
      55% cases, fall from height--in 17%, transport trauma--in 14.3%, knife wound--in
      4.4%, gunshort wound--in 1.3%. Isolated trauma of UGS was in 481 (79.1%)
      patients. In other patients combined injury of UGS with injury of skeleton's
      bones (53), cranium and brain (25), abdominal organs (20) was diagnosed. In 29
      patients severe combined trauma of UGS, abdominal organs, skeleton bones and
      cranium was seen. Surgeries were performed in 267 patients. Surgeries on kidney
      and urinary bladder due to their disruption predominated. In 44 patients these
      surgeries were combined with ones on abdominal organs. Surgery was performed in
      two stages in 25 patients with combined trauma of UGS and other organs. From 608
      patients 552 (90.2%) cured. Lethal outcome was in 56 (9.2%) patients due to
      progressive traumatic shock.

PMID- 12792964
TI  - [Successful treatment of stomach phlegmon].

PMID- 12792965
TI  - [Laparoscopic cholecystectomy in a female patient with a history of 11 surgeries
      on abdominal wall and abdominal organs].

PMID- 12792966
TI  - [Aneurysm of the splenic artery, complicated by bleeding into intestine].

PMID- 12792967
TI  - [Surgical treatment of choledochoduodenal fistula].

PMID- 12792968
TI  - [Off-pump surgical treatment of ischemic heart disease].

PMID- 12792969
TI  - [Navy senior surgeons in the years of Great Patriotic War. 58th anniversary of
      the Great Victory].

PMID- 12792970
TI  - Growth factors, cytokines, chemokines and neuropeptides in the modeling of T
      cells. Part II: Data tables of normal values in man.
AB  - Members of the T lymphocyte lineage belong to a highly reactive cell system
      engaged in the control of internal homoeostasis and bodily intactness. It
      fulfills its commitments in close communication with the cellular and non
      cellular microenvironment and with neuroendocrine regulatory mechanisms. The
      tools of such communication are various substances and compounds identified as
      cytokines, chemokines, hormones, growth factors, neuropeptides and components of
      the extracellular matrix. In a previous publication (22) we described the major
      players in the network regulation of T cell development and function as a basis
      for a computational modeling study. The present paper summarizes normal reference
      values for serum and/or plasma concentrations of these factors in man.

PMID- 12792971
TI  - Combination of radiation and vaccination with autologous tumor cells expressing
      IL-2, IFN-gamma and GM-CSF for treatment of murine renal carcinoma.
AB  - BACKGROUND: We previously showed, in a murine renal cell carcinoma (RCC) model,
      that lung irradiation plus vaccination with autologous tumor cells producing
      recombinant interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) (Renca/cytokine) reduces the number
      of lung metastases by over 90%. The present study investigates the host cellular
      mechanisms mediating this anti-tumor activity. MATERIALS AND METHODS: Lung
      metastases were produced by injection of BALB/c mice i.v. with wild-type Renca
      cells (wt Renca) on day 0. The mice were then injected s.c. with irradiated
      Renca/cytokine vaccine cells on days 4, 8 and 11. Lungs were irradiated (300
      rads) on day 7. Natural killer (NK) cells or T cells were depleted by injection
      i.p. with an antibody against anti-asialo GM1 or Thy1.2, respectively.
      Polyinosinic-polycytidylic acid (poly I:C) was injected i.p. to activate NK
      cells. Lung tumors were enumerated on day 21. RESULTS: The anti-asialo GM I
      antibody totally abolished the antitumor activity elicited by the combined
      vaccination/radiation treatment regime. In contrast, anti-Thyl.2 antibody did not
      significantly decrease treatment efficacy. Poly I:C elicited over 95% reduction
      in lung metastases and strong NK activation as assayed against YAC-1 cells in
      vitro. CONCLUSIONS: It appears that NK cells and granulocytes are predominantly
      involved in the antitumor action elicited by the cytokine-secreting autologous
      tumor cell vaccine in this metastatic RCC model.

PMID- 12792972
TI  - Effects of gentamicin on the recovery of renal function after unilateral
      hydronephrosis.
AB  - BACKGROUND: Urinary tract infection is a complication of hydronephrosis and
      antibiotics such as gentamicin are indicated for treatment. However, gentamicin
      can cause drug-induced nephropathy in dehydrated patients. We used a rat kidney
      model to investigate the effects of gentamicin administration on functional
      recovery from unilateral hydronephrosis. MATERIALS AND METHODS: Gentamicin was
      intraperitoneally injected twice for 48 hours following the release of a
      unilateral ureteral obstruction. The function of both kidneys was separately
      quantified by Technetium-99mDMSA renoscintigraphy. We examined morphological
      changes in renal tubular cells by electron microscopy and by in situ DNA 3'-end
      labeling. RESULTS: Renal function in the contralateral, but not the obstructed,
      kidney was significantly damaged by gentamicin administration under our
      conditions and electron microscopy confirmed the presence of myeloid bodies in
      renal tubular cells. In situ DNA 3'-end labeling revealed characteristic damage
      to the renal tubules. CONCLUSION: These results suggest that damage to each
      kidney should be considered individually after gentamicin administration during
      recovery from hydronephrosis.

PMID- 12792973
TI  - Effect of ulinastatin on microcirculation during excessive hemorrhage using fluid
      therapy.
AB  - Microcirculation kinetics during excessive hemorrhage and fluid therapy under
      anesthesia, with or without treatment with ulinastatin (urinary trypsin
      inhibitor), was studied by using the rabbit ear chamber. Sixteen rabbits were
      divided into 2 groups: 8 rabbits without ulinastatin treatment (group C) and 8
      rabbits treated with ulinastatin (group U). The vascular diameter, blood-flow
      velocity, blood-flow rate and urinary output were maintained well in the
      ulinastatin group as compared to those in the control group. It is concluded that
      ulinastatin is effective in maintaining microcirculation during excessive
      hemorrhage and fluid therapy at the same volume.

PMID- 12792974
TI  - Paclitaxel affects the amounts of the N-acetylation of 2-aminofluorene and DNA-2
      aminofluorene adduct formation in Sprague-Dawley rats.
AB  - BACKGROUND: The effects of paclitaxel on the in vivo distribution and the levels
      of N-acetylation of 2-aminofluorene (AF) and AF-DNA adducts in Sprague-Dawley
      (SD) rats were studied. METHODS AND RESULTS: For in vivo examination,
      pretreatment with paclitaxel (50 mg/kg) 48 hours prior to the administration of
      AF (50 mg/kg) resulted in a 28% and 43% decrease, respectively, in the urinary
      and fecal recovery of N-acetyl-2-aminofluorene (AAF), and a 22% decrease in the
      metabolic clearance of AF to AAF. Paclitaxel did not affect the Michaelis-Menten
      parameters for N-acetyltransferase (NAT) activity in blood, liver, lung, colon
      and bladder. Similarly, the Km value for AF in the examined tissues was not
      affected by paclitaxel. However, the Vmax value estimate of liver NAT activity
      was significantly decreased after paclitaxel pretreatment. Following exposure of
      rats to AF with and without pretreatment with paclitaxel, DNA-AF adducts were
      examined in the target tissues, liver, colon and bladder, and also in non-target
      tissues, lung and circulating leukocytes. The DNA-AF adducts in the liver,
      bladder, lung, colon and leukocytes were decreased by pretreatment with
      paclitaxel. CONCLUSION: This is the first finding to show that paclitaxel affects
      AF distribution and N-acetylation and DNA adduct in SD rats in vivo.

PMID- 12792975
TI  - Reversal of multidrug resistance in mouse lymphoma cells by phenothiazines.
AB  - Various compounds were tested with regard to their reversal of multidrug
      resistance (MDR) in mouse tumor cells transfected with the human MDR1 gene.
      Phenothiazines containing aromatic moieties were bound through stacking
      interaction involving the polarization of the aromatic aminoacid substituents at
      the target site of p-glycoprotein (Pgp) 170, as a consequence of their large
      dipoles (as in the binding of phenothiazine to calmodulin-like structures).
      Acting as a calcium channel blocker, verapamil may induce conformational changes
      in the calcium channel-like structures of the transmembrane regions of Pgp. Most
      probably the tyrosine moieties of Pgp are involved in the action of verapamil and
      phenothiazines. Tomato lectin specifically binds to the polylactosamine moiety of
      Pgp170 at the first loop of Pgp. Other targets in the membrane may exist in close
      proximity to Pgp170, such as conA-reactive glycoproteins with terminal mannosyl
      residues. WGA-reactive N-acetyl glucosamine residues can also be modified
      resulting in conformational changes in trans-membrane regions of the ABC
      transporter. Our results demonstrate that MDR can be reversed by interaction of
      various compounds with Pgp or by modification of the membrane structure around
      the Pgp.

PMID- 12792976
TI  - Pleural effusion in temporal arteritis.
AB  - A 73-year-old woman was admitted to hospital with a one-month history of temporal
      headache, low-grade fever, fatigue, nocturnal sweats and pleural pain. On the
      fifth day after admission she developed chest pain at the left site of the
      thorax, productive cough and progressive dyspnea. A pleural effusion was revealed
      on physical examination, as well as a bilateral temporal artery thickening. An
      erythrocyte sedimentation rate of 135 mm in the 1st hour was found. Chest X-ray
      showed left pleural effusion. Thoracocentesis revealed serous fluid exudate. A
      percutaneous pleural biopsy showed only minimal inflammatory changes. Temporal
      artery biopsy showed giant cell arteritis. The patient received prednisone 60
      mg/daily with a dramatic clinical response. Pleural effusion is a rare
      manifestation of temporal arteritis; only seven cases have been reported
      worldwide. We present a new case of temporal arteritis with pleurisy.

PMID- 12792977
TI  - Efficacy of lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide
      gene therapy for ovarian cancer.
AB  - Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into
      tumor cells using virus-based vectors in conjunction with ganciclovir (GCV)
      exposure provides a potential gene therapy strategy for the treatment of cancer.
      Effective gene therapy depends on the efficient transfer and specific targeting
      of therapeutic genes and their protein products to target cells. The purpose of
      this study was to investigate the anti-tumor effect of Lentivirus-mediated and
      MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse
      models were generated with intraperitoneal injection of human epithelial ovarian
      cancer cells 3AO, which are MUC1-positive, HIV-1-based lentiviral vectors
      carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected
      intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK, followed by
      GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK
      with GCV inhibited the proliferation and prolonged survival times compared with
      the control vector. The survival time of animals treated with scFv-VP22-TK/GCV
      was significantly longer than that of animals treated with VP22-TK/GCV (p =
      0.006). CONCLUSION: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV
      suicide gene therapy can efficiently inhibit ovarian tumor growth and increase
      survival in a nude mouse model of ovarian carcinoma. These data support the
      development of this method for human clinical trials.

PMID- 12792978
TI  - Effects of the CDT6/ANGX gene on tumour growth in immune competent mice.
AB  - BACKGROUND: Cornea-derived transcript 6 (CDT6, also known as AngX) has been
      described to inhibit tumour growth in a human melanoma growing in nude mice. In
      another report, however, enhancement of tumour growth in comparable circumstances
      occurred. We therefore studied the effect of the same gene in different
      circumstances, using an immune competent mouse model. MATERIALS AND METHODS: In
      this report we describe the generation of a stably CDT6-expressing clone of the
      murine melanoma cell line B16-F10. These cells were implanted in female C57/B16
      mice with empty vector transfected cells as control. RESULTS: We found no
      significant inhibition or stimulation of either lag-time or doubling-time of the
      tumours. In addition no effect of the CDT6 gene product was found on
      proliferation of endothelial cells in vitro. CONCLUSION: In contrast to an immune
      deficient mouse model, no anti-tumour effect could be detected with the CDT6 gene
      product in an immune competent mouse model.

PMID- 12792979
TI  - Galactoside-specific misletoe lectin modulates dexamethasone-induced apoptosis
      and glucocorticoid receptor level in Balb/c thymocytes.
AB  - The galactoside-specific plant lectin, Viscum album agglutinin-(VAA)-I has been
      shown to activate the natural immune system and modulate the maturation of
      thymocytes in vivo. However the mechanism of this immunobiological action is not
      yet understood. In our previous study we demonstrated the VAA-I-induced
      enhancement of proliferation and selection of thymocytes which inhibited the
      dexamethasone (DX)-induced thymocyte depletion. In this present work we
      investigated the effect of 1, 4 and 21 days of VAA-I treatment on DX-induced
      apoptosis of thymocytes in Balb/c mice. The number of early apoptotic cells was
      detected with Annexin V staining while the late apoptotic cells were identified
      according to their propidium iodide incorporation into DNA using flow cytometry.
      The expression of glucocorticoid receptor (GCR) in double-negative (DN), double
      positive (DP) and CD4 or CD8 single-positive (SP) cell populations was assessed.
      The additive effect of lectin on DX-induced apoptosis of thymocytes consisted of
      two different actions of VAA-I and DX. One-day VAA-I treatment caused enhanced
      apoptosis in SP mature cells in contrast to the apoptotic effect of DX, which was
      mainly directed towards immature DN and DP cells. Treatment with 30 ng/kg VAA-I
      for four days elevated the GCR level (mean fluorescence intensity) in DP
      thymocytes. Lectin treatment for 21 days caused more than 20% elevation of GCR
      expression in all thymocyte subpopulations (DN, DP, CD4+ and CD8+). These results
      suggest that VAA-I may alter the sensitivity of thymocytes to glucocorticoids and
      this effect may play a role in the bell-shaped dose-response curve of lectin
      induced immunological effects.

PMID- 12792980
TI  - Effect of vitamin C, E-acetate and beta-carotene on the cytostatic activity of
      nicotinamide (vitamin B3).
AB  - From experiments in vitro (E. coli bacteria AB 1157) it was established that the
      cytostatic activity of nicotinamide (vitamin B3) in aqueous, aerated media (pH =
      7.4) under irradiation with gamma-rays can be strongly enhanced in the presence
      of antioxidant vitamins. Whereas the addition of beta-carotene (beta-car)
      increases nicotinamide activity by a factor of 1.7, vitamin E (vit.E) of 2.16 and
      vitamin C (vit.C) of 2.3, in the presence of all three vitamins (beta-car, vit.E
      and C) a four times enhancement is observed. This ability of the vitamins to
      affect so strongly the cytostatic properties of nicotinamide is of interest for
      the radiation therapy of patients.

PMID- 12792981
TI  - Mitomycin C radical cation studied by pulse radiolysis.
AB  - The formation of the radical cation of mitomycin C (MMC.+) was investigated in
      aqueous solution by a pulse radiolysis method using SO4.- species as one electron
      oxidizing agent. The spectroscopic and kinetic characteristics of MMC.+
      transients were determined, namely: absorption maxima at 295, 400 and 500 nm, the
      corresponding molar extinction coefficients are [symbol: see text] 295 = 5.63 x
      10(3) dm3 mol-1 cm-1, [symbol: see text] 400 = 2.9 x 10(3) dm3 mol-1 cm-1,
      [symbol: see text] 500 = 2.32 x 10(3) dm3 mol-1 cm-1; the rate constant for
      formation of MMC.+ is k = (1.2 +/- 0.2) x 10(10) dm3 mol-1 s-1 and for decay 2k =
      (4.6 +/- 0.4) x 10(8) dm-3 mol-1 s-1. Based on this fact it can be assumed that
      not only the well-known mitomycin C radical anion (semiquinone, MMC.-) is
      efficiently involved in the radiotherapy process, but in a given oxidation
      environment the MMC.+ species could also play a role in this respect.

PMID- 12792982
TI  - Effects of eparlestat on plasma levels of advanced glycation end products in
      patients with type 2 diabetes.
AB  - Advanced glycation end products (AGE) are produced by a nonenzymatic reaction
      between glucose and proteins in the plasma of diabetic patients. Recently, AGE
      have been reported to promote and accelerate diabetic complications and
      atherosclerosis. The activity of aldose reductase (AR) is increased in diabetic
      patients. AGE are reported also to be produced by increased levels of fructose
      through increased activity of AR in diabetes. Consequently, we administered
      eparlestat, one of AR inhibitors, to diabetic patients and investigated the
      plasma carboxymethyl-lysine (CML) concentration, one of the AGE, before and after
      the administration of eparlestat. Though plasma CML concentration did not show
      any significant changes in all patients after the administration of eparlestat in
      the present study (from 2.7 +/- 0.3 mU/mL to 2.5 +/- 0.2 mU/mL; 3 months, 2.9 +/-
      0.3 mU/mL; 6 months), plasma CML concentration were significantly decreased 3
      months after the administration of eparlestat in the patients whose CML
      concentration before the treatment was higher than 3 mU/mL (from 3.4 +/- 0.2
      mU/mL to 2.6 +/- 0.2 mU/mL; 3 months, p = 0.017). Serum thrombomodulin and HbA1c
      levels did not show any significant changes. These results suggest that the
      administration of eparlestat may be beneficial in preventing diabetic
      complications by decreasing plasma CML in diabetic patients.

PMID- 12792983
TI  - Changes in hemopoietic precursors after treatment of low-risk myelodysplasia with
      amifostine.
AB  - BACKGROUND: Clinical studies have shown that amifostine (AMF) improves peripheral
      cytopenias in myelodysplastic syndromes (MDS). We studied the expression of
      Fas/FasL on CD34+ cells in low risk MDS and its change after AMF treatment.
      PATIENTS AND METHODS: Patients received AMF 400 mg/m2 3x/week for 3 weeks and 2
      weeks off treatment. Peripheral blood counts and BM cytology were analysed before
      and after 2 courses. Quantification of CD34+ cells and CD34/CD95 and CD34/CD95L
      ones were performed by flow cytometry. RESULTS: Seventeen patients were treated.
      After 2 months, 8 patients showed a rise in neutrophil count. Hemoglobin
      increased in 1 and thrombocytes in 2 patients. Before treatment, responding
      patients presented a significantly lower expression of Fas (median 53%) and FasL
      (median 26%) than non-responders (85% and 70%, respectively). BM lymphocytes were
      significantly lower in responders (median 14.5% and 27.4%, respectively). In
      responders CD34+ cells decreased after treatment. The change in neutrophil count
      after treatment presented an inverse correlation with the percentage of BM
      lymphocytes before treatment (r = 0.0-0.58; p = 0.02). CONCLUSION: Response to
      AMF may be influenced by the intensity of the immune reaction in BM.

PMID- 12792984
TI  - Apoptosis: a mechanism of cell suicide.
AB  - In this paper, a general overview on apoptosis (or programmed cell death) is
      given together with a brief description of the major features characterizing
      apoptotic cells. Then the most important pathways of apoptosis are described.
      Thereafter the roles of caspases and the Bcl-2 family members on apoptosis are
      explained.

PMID- 12792985
TI  - Screening of gastrointestinal hormone release in patients with lung cancer.
AB  - The aim of this study was the screening of gastrointestinal (GI) hormones release
      as possible sensitive tumor markers. The subjects were eight patients with
      carcinoma of the lung compared with nine healthy controls. Six kinds of GI
      hormones were measured by the specific radioimmunoassay. It was evaluated by
      fasting level (F), increased integrated responses (IIR60, IIR180 pmol/l/min) and
      total integrated responses (TIR60, TIR180 pmol/l/min) after a meal. The data were
      analyzed by the Student's t-test. The F of pancreatic polypeptide (PP) was
      significantly higher in patients than that in healthy controls (24.4 vs. 12.3
      pmol/l, p = 0.002). Consequently, the sensitivity was 75% (6 out of 8) and
      specificity was 100% (9 out of 9). Almost all parameters of IIR60, IIR180, TIR60
      and TIR180 in PP and peptide YY were significantly higher in patients than in
      healthy controls (p value: 0.00020-0.021). The other four kinds of hormones
      showed similar results to the healthy controls. These results seem to indicate
      that PP and PYY would be useful tumor markers for lung cancer in clinical
      management.

PMID- 12792986
TI  - Evaluation of caffeine as a radioprotector in whole-body irradiated male mice.
AB  - Caffeine is the main psychoactive ingredient of coffee, tea and even colas. This
      study investigated the radioprotection of caffeine in mice. Mice were irradiated
      with 6.5 Gy. A caffeinetreated group was administered 80 mg/kg-body weight by an
      i.p injection at 1 hour before irradiation. At 6 hours after irradiation, the
      animals were sacrificed for the study. Hormonal analysis was performed with
      radioimmunoassay on serum. The expression kinetics of the apoptotic genes after
      irradiation was evaluated with RT-PCR. The weight of body and organ and H and E
      stained slides did not show differences between groups. The circulating
      testosterone significantly decreased in the irradiated group. The expression of
      Fas antigen, p21, p53, bax and bcl2 related to radiation- induced apoptosis was
      comparable to that of the caffeine-untreated group. Bax mRNA dramatically
      increased in the irradiated group, but not in the irradiated caffeine -treated
      group. The results indicate that caffeine protects an early apoptotic initiation
      after irradiation.

PMID- 12792987
TI  - Matrix metalloproteinases 2 and 9 in follicular fluids of patients undergoing
      controlled ovarian stimulation for ICSI/ET.
AB  - The objective of this study was to detect the level of matrix metalloproteinases
      2 and 9 in the follicular fluid of patients undergoing controlled ovarian
      stimulation and to correlate these levels with hormonal and clinical parameters.
      Follicular fluids were collected from thirty patients participating in an
      intracytoplasmic sperm injection/embryo transfer (ICSI/ET) program in "Otmar
      Bauer" Assisted Reproduction Center, Alexandroupolis, Greece. Follicular fluid
      was collected at oocyte retrieval and MMP-2 and MMP-9 were identified by gelatin
      zymography. Gelatin zymography of the follicular fluids revealed bands consistent
      with proMMP-2 and proMMP-9. ProMMP-2 was the predominant band in the majority of
      samples. The levels of MMPs varied considerably among the samples. A significant
      positive correlation between MMP-2 and the peak estradiol levels was found.

PMID- 12792988
TI  - Effect of high sucrose diet on liver enzyme content and activity and aflatoxin B1
      induced mutagenesis.
AB  - Aflatoxin B1 (AFB1) is a fungal toxin and contaminant that has been implicated in
      human liver carcinogenesis. In this study we evaluated the effect of a 65% of
      total calories from sucrose diet (HSD) for 90 days on hepatic cytochrome P450
      (CYP450) and glutathione-S-transferase (GST) activity compared to rats maintained
      on standard lab chow (0% sucrose). There was a statistically significant increase
      in the number of S. typhimurium His+ revertants (p < 0.001) generated from the
      incubation of AFB1 with hepatic microsomes from rats fed a HSD. The HSD did not
      affect the total microsomal CYP450 content nor content of CYP450 1A2, 2B1, 2
      isoforms which activate AFB1. Alkoxyresorufin O-dealkylase activity (MROD, PROD)
      of microsomes from animals fed HSD was decreased by 73% and 49%, respectively.
      MROD activity is linked to CYP 1A2 activity while PROD is linked to CYP 2B1,2
      activity. Although the amount of CYP 3A was significantly decreased in rats fed a
      HSD, its activity, determined by the presence of the fluorometric metabolite 7
      hydroxyquinidine, was unchanged. GST activity was significantly lower in the rats
      fed HSD.

PMID- 12792989
TI  - Apoptosis in growing hair follicles following gamma-irradiation and application
      for the evaluation of radioprotective agents.
AB  - The usefulness of apoptotic fragments assay for investigating the radiation
      response of hair follicles and evaluation of radioprotective agents was examined
      in ICR mice. The extent of changes following 100 cGy (1000 cGy/min) was studied
      at 0, 2, 4, 8, 12, 16 or 20 hours after exposure. The maximal frequency was found
      12 hours after exposure. The mice that received 50, 100, 200, 400 or 800 cGy of
      gamma-rays were examined 12 hours after irradiation. Measurements performed after
      gamma-ray irradiation showed a dose-related increase in apoptotic cells in each
      mouse studied. The dose-response curves were analyzed with a linear-quadratic
      model: the frequency (number per follicle) of apoptotic cells in the hair
      follicle was y = (0.05527 +/- 0.009574) D + (-0.00001988 +/- 0.00001337) D2 +
      0.227 (r2 = 0.964, D = 100 cGy). The frequency of radiation (100 cGy)-induced
      apoptosis in hair follicles was reduced by pretreatment of diethyldithiocarbamate
      (DDC, i.p. at 30 minutes before irradiation, p < 0.05) or green tea (i.p. at 12
      and 36 hours before irradiation, p < 0.01). From these results, it is thought
      that this model will be useful in the detection of radiation response and
      radioprotective agents.

PMID- 12792990
TI  - [Teratogenicity of bisphenol A on post-implanted rat and mouse embryos: an in
      vitro study].
AB  - In order to evaluate the developmental toxicity of BPA and to investigate the
      possible mechanism of it in vitro, whole embryo culture was used for the study.
      The embryos that removed from mother mice on gestational 8.5d (GD8.5) and mother
      rats on gestational 9.5d (GD9.5) were cultured immediately in centrifugal serum
      (ICS) with a series of concentrations of 0, 40, 60, 80, 100 mg/L of BPA for 48 h
      to evaluate the embryo development and morphological differentiation. The results
      showed that the BPA inhibited the development of embryos in vitro and there was a
      dose-response relationship between concentrations of BPA. At high level (> or =
      60 mg/L), BPA could delayed the growth and cardiac tube differentiation of
      visceral yolk sac (VYS), and induced various embryo defects, including abnormal
      neural system, arch, optic, flexion and small limb bud, etc. It is concluded that
      at high level, BPA had toxicity to mice and rat embryos in vitro. The damage on
      structure and function of VYS might be part of teratogenic mechanisms of BPA.

PMID- 12792991
TI  - [Study on the relationship between proliferative activities and heat stress
      protein 70 expression of aortic endothelial cells by benzo(a) pryene].
AB  - In order to investigate the relationship between proliferative activities and
      heat stress protein 70(HSP70) expression of porcine aortic endothelial cells(ECs)
      treated by benzo(a) pryene in vitro, porcine aortic endothelial cells were
      cultured in vitro, treated by different concentration of BaP(0, 0.5, 1, 10, 20
      mumol/L) for 24 hours. Then, the proliferative activities and HSP70 expression of
      endothelial cells were determined by MTT and Western-blot respectively. The
      results showed that along with the rise of concentration of BaP, proliferative
      activities of porcine aortic endothelial cells decreased. There are not
      significantly difference of expression of HSP70 between and control and low
      exposed cultures(0.5 mumol/L), but decreased at intermedieate and high
      concentration(1, 10, 20 mumol/L). It was suggested that BaP restrained
      proliferative activities of porcine aortic endothelial cells, which may be
      related to the inhibition of HSP70 expression by BaP.

PMID- 12792992
TI  - [Study on denitrification using different carbon sources].
AB  - In this study, bench scale tests were conducted to study the potentials of
      immobilized denitrifier to reduce nitrate in the presence of 4 different carbon
      sources: glucose, cane sugar, methanol and acetic acid. The results showed that
      the carbon sources can be used by the immobilized bacteria as exogenous carbon
      sources. While using methanol, the average denitrifying velocity was lower than
      the others. Dissimilatory reduction to ammonium was not significant and accounted
      for less than 5% of reduced nitrate. By a 6-hour hydraulic residence time, the
      denitrification rates were higher than 96%. The nitrate enriched water of S lake
      was also treated by the immobilized denitrifier to study the character of
      denitrification, especially on the using of natural carbon sources as electron
      donotor. The results showed that more than 90% of the nitrate in the water could
      be reduced by the immobilized bacteria, and more than 20% of the natural carbon
      sources in the water could be used by the immobilized cells.

PMID- 12792993
TI  - [Study on guideline of alga in source water].
AB  - Toxic bloom in the sources of drinkable water has been a public health problem.
      Hindered by the complicated analysis procedure, very limited efforts has been
      done in investigating toxin level. Patronized by the Chinese Academy of
      Preventive Medicine, a study on alga hygiene criteria of drinkable water sources
      in China was conducted. Available literature was reviewed and ecological research
      and toxicological tests were carried out. The criteria on alga biomass in
      drinkable water source was formulated by referring the criteria of microcystin-
      LR in drinking water recommended by WHO and Ministry of Health, China. Three
      kinds of criteria were worked out: primary criteria, which is to ensure safety,
      is 1.0 x 10(4) per liter, secondary criteria, which should be alert, is 2.1 x
      10(5) per liter, and third--rate criteria, which might be toxic, is 1.2 x 10(6)
      per liter. It is suggested that these criteria are valuable and feasible in
      routine work.

PMID- 12792995
TI  - [Effect of SO2 inhalation on the levels of GSH and GSH/GSSG in 9 organs of mice].
AB  - By spectrophotometric method, the level of non-enzymatic antioxidant glutathione
      (GSH) and the ratio of GSH/GSSG were examined in nine organs of mice of both
      sexes after exposed to sulphur dioxide (SO2) at several concentrations. The
      results showed that: (1) at 22 mg/m3 of SO2 inhalation concentration, there were
      no significant difference between the experimental and control mice for the GSH
      levels and GSH/GSSG ratio in all of tested organs; (2) at 64 mg/m3, the GSH
      levels were significantly decreased in lungs, kidney, brain, stomach and testicle
      of the male mice in the experimental group, while the GSH levels and GSH/GSSG
      ratios in the tested organs of the female mice had no marked changes in the
      comparison with those in the control group; (3) 148 mg/m3 of SO2 inhalation led
      to decrease of both the GSH levels and GSH/GSSG ratios, in that the GSH levels
      were significantly lowered in liver, lung, kidney, heart, brain, stomach, small
      intestine and testicle of the male mice and in liver, lung, kidney, small
      intestine of the female mice, and the GSH/GSSG ratios were in liver, kidney,
      small intestine and testicle of the male mice and in liver, lung, kidney, brain,
      stomach, small intestine of the female mice. It indicated that SO2 above certain
      concentration could make effects not only on respiratory organ, but also on other
      organs, and the susceptibility of the male and the female mice to SO2 was
      different. The decline of the GSH level and GSH/GSSH ratio suggests that the
      toxic effect of SO2 is associated with its lowering the levels of antioxidants
      and weakening the defense system and antioxidation in organisms.

PMID- 12792994
TI  - [Study on the unscheduled DNA synthesis in primary rat hepatocyte induced by
      source water, tap water and active carbon-treated tap water].
AB  - To study the mutagenicity of source water with different turbidities, tap water
      and active carbon-treated tap water, unscheduled DNA synthesis in primary rat
      hepatocyte was detected. Increased unscheduled DNA synthesis was found in a dose
      depend manner inducted by tap water, source water and tap water treated with 5,
      10 and 15 milligrammes active carbon per liter water. The results also showed
      that the mutagenicity of the source water increased with the increasing of its
      turbidity, and mutagenicity of the tap water is higher than that of the source
      water as well. There was no unscheduled DNA synthesis in tap water followed by
      the treatment with 20 milligrammes active carbon per liter water. It is suggested
      that the development of the water treatment technics including sedimentation,
      filtration and treatment with active carbon is needed for decreasing or
      eliminating the mutagenicity of tap water.

PMID- 12792996
TI  - [Improvement of the silver-stain and it's test and verification in comet assay].
AB  - In order to find out a better silver-stain method so that to replace EB-stain in
      comet assay, the selected silver-stain methods were tested via determining
      fixing, coloring, displaying, fading, and testing the pigmentation temperature.
      When it was optimized, it was used in testing the DNA damage by two types of
      compounds, namely potassium dichromate (K2Cr2O7) and 1,2-dichloroethane (DCE) to
      two kind of cells, namely spleen cells of mouse and human outer lymphocyte, and,
      the sensitivity was compared with that of EB-stain. The results showed that the
      modified silver-stain was the first successful non-fluorescent dye method in
      comet assay that can dye clearly, permanently, with a light background and good
      contrast, and it was easy to manipulate and it was cheap. The stain can detect
      the DNA damage by compounds to cells and has the same positive threshold like
      that in EB-stain. It can even dye the small fragments that EB-stain cannot. It is
      suggested that in comet assay, the silver-stain can substitute the EB-stain
      completely.

PMID- 12792997
TI  - [Effects of chromium and fish oil on blood lipid and blood glucose in obese
      rats].
AB  - Obesity does great harm to people's health. In order to study the effects of
      chromium and fish oil on blood lipid and blood glucose in obese rats, 32 obese
      model rats were divided randomly into four groups: fish oil group(5 ml/kg BW),
      chromium group(3 mg/kg BW), fish oil + chromium group and high fat diet group. In
      the end of the experiment(6 weeks) fats around kidney and spermary were weighted
      and blood samples were collected to determine blood glucose and blood lipid.
      Result shows that blood glucose and blood lipid in experimental groups were lower
      than those in high fat diet group. The ratios of fats around kidney and/or around
      spermary to body weight in experimental groups were lower than those in high fat
      diet group. CONCLUSION: Chromium and fish oil decrease the risk of obese relative
      diseases.

PMID- 12792998
TI  - [Research on the gap junctional intercellular communication of CHL cells and
      human cancer cells induced by c9, t11-conjugated linoleic acid].
AB  - In order to determine the effects on the gap junctional intercellular
      communication(GJIC) of CHL cells and human cancer cells induced by c9, t11-CLA
      and its mechanism. GJIC was observed by using scrape loading and dye
      transfer(SLDT) on CHL cells blocked by TPA and cancer cells(SGC-7901 and MCF-7)
      which were treated with various c9, t11-conjugated linoleic acid (CLA)
      concentrations (25, 50, 100 and 200 mumol/L) of c9, t11-CLA for 24 and 48h, with
      a negative control. The results showed that c9, t11-CLA can recover GJIC of CHL
      cell blocked by TPA and similar to negative control at 200 mumol/L 48 h of c9,
      t11-CLA; c9, t11-CLA also can recover cancer cells(SGC-7901 and MCF-7) at doses
      of 24 h 100 mumol/L for MCF-7 cells and 24 h 200 mumol/L, 48 h 100 mumol/L, 200
      mumol/L for SGC-7901 and MCF-7 cells. It was suggested that c9, t11-CLA can
      recover GJIC of CHL cells blocked by TPA and SGC-7901 and MCF-7 cells.

PMID- 12792999
TI  - [Effects of c9, t11-conjugated linoleic acid on the metastasis of human gastric
      carcinoma cell line].
AB  - In order to study the effects of c9, t11-conjugated linoleic acid on the invasion
      of human gastric carcinoma cell line(SGC-7901) and explore its possible
      mechanism, the five levels of CLA in medium were designed as 0, 25, 50, 100 and
      200 mmol/L respectively. After SGC-7901 were treated with c9, t11-CLA for 24
      hours, the reconstituted basement membrane invasion assay was used to evaluate
      invasive ability of cancer cells. The type IV collagenase was assessed by PAGE
      substrate zymography and the expression of TIMP-1 and TIMP-2 mRNA was measured by
      RT-PCR. The result displayed that c9, t11-CLA could inhibit the reconstituted
      basement memebrane invasion, reduce type IV collagenase activities in the serum
      free supernatant of SGC-7901 cells and induce TIMP-1 and TIMP-2 mRNA expression
      in SGC-7901 cell line. Therefore, it is suggested that CLA could inhibit the
      reconstituted basement membrane invasion of SGC-7901 cells and the anti-invasion
      action of c9, t11-CLA might be associated with the reduction of type IV
      collagenase activity in tumor cell culture supernatant and induction of tumor
      cell TIMP-1 and TIMP-2 mRNA expression.

PMID- 12793000
TI  - [Effect of nuts enrich in monounsaturated acid on serum lipid of hyperlipidemia
      rats].
AB  - In order to observe the regulatory effect of monounsaturated acid-enriched almond
      and macadamia nuts on blood lipid-level (TC, TG, HDL-C), the hyperlipidemia
      Wistar rats were used as the model and a diet containing almond and macadamia at
      the doses of between 12.5% and 25.0% was given for six weeks. The results showed
      that the level of the serum TC and TG in each study group was significantly lower
      than that of high fat chow control group (P < 0.05). There was a significant
      increase (P < 0.05) in the serum HDL-C level in the high fat chow group with high
      dose macadamias compared with that in the high fat chow control group. The
      findings suggested that nuts enrich in monounsaturated acid could decrease the
      level of serum TC and TG and macadamias could increased the level of serum HDL-C
      in the hyperlipidemia rats.

PMID- 12793001
TI  - [Study of the effects of isoflavone on serum lipid and bone biochemical markers
      in ovariectomized rats].
AB  - The effects of isoflavone on serum lipid and bone biochemical markers in
      ovariectomized rats were studied. Four-month old Wistar rats were divided into 6
      groups according to their weights. Rats were either sham-operated or
      ovariectomized (ovx). Some ovx rats were given different dosage of isoflavone or
      estrostilben. Sixteen weeks later, the rats were killed and the serum were
      separated to determine the analytical indexes. The experiment results show that
      in the group of isoflavone the content of serum HDL and bone formation index bone
      gamma-carkoxyglutamate protein (BGP) increase, but total cholesterol (TC),
      triglycerides (TG) and bone absorption index tartrate-resistant acid phosphatase
      (TRAP) decrease obviously. The results from this study indicate that isoflavone
      can modulate serum lipid and inhibit bone absorption.

PMID- 12793002
TI  - [Genistein induced apoptosis in MCF-7 and T47D cells].
AB  - Dietary genistein, a natural flavone compound found in soy, has been proposed to
      be related to the lower prevalence of breast cancer in Asian women. In order to
      elucidate the mechanism of chemopreventive effect of genistein so that to provide
      more scientific basis for dietary intervention for breast cancer in women, the
      apoptosis in estrogen responsive breast cancer cell lines (MCF-7 and T47D cells)
      was induced as the study model and the effect of genistein on the apoptosis was
      observed. The results showed that, functionally similar to the anti-estrogen
      tamoxifen, genistein induced in a dose- and time-dependent manner the MCF-7 cell
      apoptosis at concentrations above 20 x 10(-6) mol/L. The findings suggested that
      the increased isoflavone intake can induce apoptosis in estrogen responsive
      cells.

PMID- 12793003
TI  - [Study on mechanisms of human gastric carcinoma cells apoptosis induced by
      genistein].
AB  - In order to study the apoptosic effect of genistein on human gastric carcinoma
      SGC-7901 cells, DAPI dyeing and DNA electrophoresis were used. Western Blot was
      used to detect the changes of the expression of p53 protein, Caspase-3 after SGC
      7901 cells were exposed to genistein. The results showed that genistein induced
      cell apoptosis. Genistein also decreased the expression of mutant p53, and
      increased the protein expression of Caspase-3. These indicated that genistein
      could induce the apoptosis of gastric carcinoma cells. The inhibition of the
      expression of mutant p53 and enhance of the protein expression of Caspase-3 would
      be possible mechanism.

PMID- 12793004
TI  - [Effect of apoptosis induced by different vitamin E homologous analogues in human
      hepatoma cells (HepG2)].
AB  - To observe the effect of alpha-tocopherol(gamma-T), delta-tocopherol(delta-T),
      delta-tocopherol(delta-T), and vitamin E succinate (VES) on apoptosis induced in
      human hepatoma cells (HepG2), the cell apoptosis was detected by flow cytometry
      (FCM) and DNA ladder under the treatment of different VE homologues analogues
      (alpha-T, gamma-T, delta-T and VES) at different concentrations (12.5, 25, 50,
      100 and 200 mg/L) for 48 hours. The results showed that the growth of HepG2 cells
      was inhibited by delta-T and VES at 12.5-200 mg/L in comparison with the negative
      control group, while gamma-T showed weak effect of inhibition and alpha-T did not
      show any inhibition effect. With the exception of alpha-tocopherol, delta
      tocopherol and VES were effective in induction of apoptosis in HepG2 cells at
      concentrations of 12.5-200 mg/L. gamma-tocopherol showed effect only at 200 mg/L.
      delta-tocopherol and VES decreased HepG2 cells growth and viability, and
      increased apoptotic propensity significantly. A dose-dependent of
      antiproliferation and induction of apoptosis were found in HepG2 cells line. The
      order of efficiency of four vitamin E analogues was delta-tocopherol > VES >
      gamma-tocopherol > alpha-tocopherol. It is suggested that delta-tocopherol and
      VES may be a agent that has a anti-hepatomatic potential.

PMID- 12793005
TI  - [Studies on protein-based identification method of genetically modified
      capsicum].
AB  - The detection system based on protein is a method to evaluate the safety of
      genetically modified foods (GMF). Using cecropin BD gene in capsicum, a detecting
      method was set up. It is a system of evaluating the real expressive condition and
      safety of the foreign target protein of GMF. In this studies, with the
      preformative technic method, a satisfactory results by making use of hemolymph of
      immunized pupae of Antheraea pernyi as standard experimental material was
      achieved, comparing with the realities of the goal protein expressive condition
      of cecropin D gene in capsicum. The detecting steps were as following: the goal
      protein from material was extracted roughly, then with CM-Sepharose-FF ion
      exchange chromatography twice, the goal protein was purified moderately. The
      purified product was identified by detecting the anti-bacterial activity,
      electrophoresis, biological auto-photography of the goal protein and MADDI-TOF
      mass spectrum. The results showed that the expressive foreign target protein in
      transgenic capsicum was in accordance with standard protein in the physical and
      chemical property, anti-bacterial activity and molecular weight. It indicated
      that expression of the target gene in capsicum is real, it corresponded to
      expected value. The separation, purification and identification methods of
      cecropin D were established in the study. By means of the comparative experiments
      about anti-bacterial activity and molecular weight of anti-bacterial peptide(ABP)
      from GM-capsicum and hemolymph of immunized pupae of Antheraea pernyi, the
      identification method of target protein from GM-capsicum was set up. The method
      is easy to be operated, fast and feasible.

PMID- 12793006
TI  - [Effects of air pollution from coal combustion on lung function in children].
AB  - In order to observe effects of air pollution from burning coal on children's
      health, Four hundred fifty junior schoolers selected from three survey sites in
      Taiyuan city with different degrees air pollution were investigated using
      questionnairing survey and the lung function were tested. The results showed that
      children's pulmonary function in survey site A is lower than site B, and site B
      is lower than site C. The prevalence of ventilation disfunction were correlated
      to the types of heating, the separation of kitchen and bedroom and the pollutants
      concentration with logistic model. Multiple linear regression analysis showed
      that compared with site C, FVC and FEF50 in site A decreased by 65.80 +/- 33.35
      ml and 119.27 +/- 78.74) ml respectively and, in site B, decreased (57.28 +/-
      31.22) ml and (114.29 +/- 58.80) ml respectively (Model 1). FVC and FEF50
      decreased by 69.10(31.50 ml and (119.79 +/- 86.82) ml respectively with one unit
      increase of Ln (SO2) (Model 2). FVC and FEF50 decreased by 193.50 +/- 65.55 ml
      and 171.69 +/- 87.11 ml respectively with one unit increase of Ln(PM10) (Model
      3). It can be concluded that the air pollution from coal consumption in Taiyuan
      city had impact on the children's lung function.

PMID- 12793007
TI  - [Brick-tea type adult bone fluorosis].
AB  - To investigate health impact of brick-tea type fluorosis in adults, the total
      daily fluorine intake, environment fluorine level were determined, the average
      urinary fluorine content assay and bone X-ray examination were conducted, the
      clinical manifestations were observed in the brick-tea type bone fluorosis
      epidemiological study conducted in Naqu County, Tibet at September, 2001. One
      hundred and eleven adults aged at 30-78 year-old were enrolled. It was found that
      the fluorine level of drinking water in Naqu County was 0.10 +/- 0.03 mg/L, but
      the brick-tea water processed foods-zamba and buttered tea had fluorine content
      of 4.52 +/- 0.74 mg/kg and 3.21 +/- 0.65 mg/kg respectively. The adult daily
      fluorine intake reached 11.99 mg, among which 99% is originated from the brick
      tea containing foods. Positive detection rate of fluorosis osteopathy was 89% and
      the X-ray film confirmed that the diagnosis rate was 83%. Degenerative
      arthropathy and ossification of the interosteal membrane, calcification of the
      tendon were the characteristics that indicated by both the positive signs and
      reogenological examination. The prevalence of osteosclerosis type (bone matrix
      increased) was 74%. It is suggested that there were even more severe health
      impact compared with those in the water type and coal combustion type fluorosis.

PMID- 12793008
TI  - [Comparison of hemoglobin level and anemia prevalence between female and male
      post-adolescent high school graduates].
AB  - OBJECTIVE: Anemia morbidity in the population of adolescent and post-adolescent
      high school student has been paid little attention. Iron deficiency anemia is one
      of common maladies of micronutrient depletions, which has been proven to be
      damaging to cognition and intelligence performance. To probe into relationship
      between possible micronutrient deficiencies among post-adolescent schoolgirls and
      their poor intelligence performance comparing with same aged boys, this
      investigation was carried out. METHODS: Blood hemoglobin levels of 2624 senior
      high school student, including 1050 females and 1754 males with average age of
      18.89 +/- 1.30 years, were determined at the time when they took part in physical
      examination for the National University Entrance Test. RESULTS: Anemic prevalence
      among female high-school graduates was 11.3%, much higher than 1.5% of males (P <
      0.001). CONCLUSION: The high anemic morbidity in post-adolescent high schoolgirls
      exists, and it may be turned up to be one of causes of dropping behind in school
      test performance to them.

PMID- 12793009
TI  - [Relations of lipoprotein lipase gene polymorphism at Pvu II locus and dietary
      intervention predisposition in hyperlipidemia population].
AB  - In order to investigate the relation of lipoprotein lipase (LPL) gene
      polymorphism at Pvu II locus and dietary intervention predisposition in
      hyperlipidemia population, 436 hyperlipidemia patients were screened selected
      from some communities in western urban districts in Beijing, and then separated
      into two groups, intervention (248) and control group(188). The serum lipids
      profile, dietary intakes data were collected and physical examination was
      conducted in all subjects. Also, the LPL-Pvu II polymorphisms were analyzed by
      PCR-RFLP. The results showed that the total energy intake, cholesterol level and
      percentage of energy from dietary fat, and the serum levels of TC, LDL-C and HDL
      C were significantly decreased (P < 0.05) after 6-month dietary intervention in
      intervention group compared with the control group. The decrease range of TC and
      LDL-C in carriers with LPL-Pvu II (+/+) genotype was much more than others(+/-
      and -/- genotypes). The results from multiple linear regression analysis showed
      that the susceptible factors of dietary intervention included LPL-Pvu II (+)
      allele, the high baseline levels of TC and LDL-C and overweight. The conclusions
      could be primarily drawn that the variants of LPL-Pvu II locus were important
      determinants of variation in serum cholesterol response to dietary change in
      hyperlipidemia population.

PMID- 12793010
TI  - [Application of randomly amplified polymorphic DNA on the DNA polymorphism of
      Staphylococcus aureus and Klebsiella pneumoniae].
AB  - By using short single oligomer primer with arbitrarily chosen sequences in
      polymerase chain reaction, randomly amplified polymorphic DNA (RAPD) was applied
      in differentiating clinical isolates of 52 Klebsiella pneumoniae and 28
      Staphylococcus aureus. RAPD produced multiple polymorphic DNA bands when K.
      pneumoniae DNA was used as template. Using DNA fingerprints technique, the
      similarity coefficients values of 52 K. pneumoniae was measured and calculated,
      and dendrogram was drawn. The 52 Klebsiella pneumoniae were divided into 7
      Patterns. But in the 28 Staphylococcus aureus, 3 characteristic lands were
      obtained. Minor differences in the RAPD fingerprints were detected. The research
      findings demonstrated that RAPD has a potential as a widely useful tool in
      providing genotypic characters for taxonomic descriptions and molecular
      epidemiology study.

PMID- 12793011
TI  - [Relationship of dengue fever epidemic to aedes density changed by climate
      factors in Guangdong Province].
AB  - In order to explore and quantify the relation between probability of dengue
      episode and aedes density, and climate factors, and also, to provide scientific
      approach for prevention and supervision of dengue fever, data on dengue fever
      cases, aedes vector's supervision and climate factors such as average air
      temperature, lowest air temperature, highest air temperature, sunlight, rainfall
      and relative humidity were collected and, were analyzed by correlation analysis,
      stepwise regression and logistic regression method. The results showed that the
      logistic regression equation: p (1) = 1/[1 + e-(-7.750 + 0.391 BI)], indicating
      that meteorology parameter correlating with breteau index(BI) were rainfall,
      sunlight, average air temperature, lowest average air temperature and relative
      humidity; by stepwise regression analysis, the regression equation: viz.: YBI =
      24.800 + 0.826 X1 + 0.020 X2 - 0.418X3, X1 representing lowest average air
      temperature, and X2 representing rainfall and X3 representing relative humidity.
      It is suggested that the influence of climate factor on vector aedes density is
      complicated. But its primary influence factors are lowest average air
      temperature, rainfall and relative humidity. The primary influence factors of
      dengue episode are breteau index.

PMID- 12793012
TI  - [Determination of total lovastatin in red rice].
AB  - In order to text effectiveness and safety of red rice products, the determination
      of total lovastatin is more optional than that of determination of its lactone
      only. The method for determination of total lovastatin is established in this
      study. HPLC method is applied with the C18 column (250 mm x 4.60 mm). Flow phase:
      water (72:28); wave length: 238 nm; Flow speed: 1.0 ml/min; column temperature:
      room temperature. Moreover, the reliability of this method validated recovery
      rate 98.3, RSD = 0.33%.

PMID- 12793013
TI  - [Development of bladder cancer chemoprevention].
AB  - Bladder cancer is one of the most common malignant tumor. The morbidity increased
      every year because of high recurrence. It is widely accepted that prevention may
      be the effective way to decrease the rate of recurrence and morbidity. Being the
      biological mechanism of bladder cancer lucubrated, several biomarkers and
      chemopreventive agents were discovered for the detection and prevention, and even
      reversion of the precancerous lesion. In this paper, the progress in bladder
      cancer chemoprevention was reviewed.

PMID- 12793014
TI  - [Nitric oxide and early inflammatory injury in silicosis].
AB  - There is a body of evidence that NO formation could be implicated in mediating
      silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only
      contribute to lung parenchymal tissue injury but also has the ability to combine
      with superoxide and form a highly reactive toxic species-peroxynitrite, which can
      induce extensive cellular toxicity via a variety of mechanisms in the lung
      tissues. Several cytokine is required for NO production. NF-kappa B plays a
      particularly important role in the regulation of gene expression of the iNOS
      isoform. There are discrepancy between the current literature regarding the role
      NO in the NF-kappa B activation and therefore, in this paper, the role of NO in
      the cellular and molecular mechanisms of silica-induced lung damage was reviewed.

PMID- 12793015
TI  - [Gene chip technology and it's application to genetic toxicology].
AB  - Gene chip, also called as DNA array, Oligonucleotide Microchip or Oligonucletide
      array, is a new technology developed in recent years. It can be applied
      prospectively in life science research, such as gene expression, gene diagnose
      and gene polymorphism etc. In this paper, the principle, types, procedures and
      application of gene chip to genetic toxicological research were reviewed.

PMID- 12793016
TI  - [Progression of study on the relationship between muscle strength, physical
      activity and bone mineral density].
AB  - Osteoporosis is a skeletal disease characterized by low bone mass and
      microarchitectural deterioration of bone tissue, with a consequent increase in
      fragility and susceptibility to fractures resulting in the severe health
      consequences to human health. Many investigations have been done in exploring the
      etiological factors so as to find out approaches for prevention and treatment of
      osteoporosis. Low bone mineral density is one of the important clinical
      characteristics of osteoporosis. In this paper, the progress of study on the
      relationship between muscle strength, physical activity and bone mineral density
      was reviewed.

PMID- 12793017
TI  - [Ochratoxin A and human health].
AB  - Ochratoxin A (OA) is produced mainly by Penicillium verrucosum, Aspergillus
      ochraceus and A. carbonarius and it was found as a contaminant in the large
      number of agricultural commodities, feedstuffs and animal organs such as kidney
      and liver of pig. Toxicological studies indicated that OA is a teratogenic,
      mutagenic and carcinogenic mycotoxin with the strong toxic effects on liver and
      kidney. In some endemic areas in the world, OA was suspected to be related to
      swine nephropathy and has been detected in blood samples from inhabitants in
      these areas as well. More and more attention was paid to the relationship between
      the consumption of food contaminated with OA and human health. In this paper, OA-
      producing fungi, the contamination of it to the agricultural commodities, its
      toxicity and risk assessment are reviewed.

PMID- 12793018
TI  - [Risk factors for cervical cancer].
AB  - In the following document a case and control study carried out in the Hospital
      General de Mexico is presented. The research obtained and analyzed facts related
      to social and cultural issues, as well as the obstetrics and gynecologist
      background, stating for each one of them, the relative risk and its statistical
      meaning with a trust degree of 95%. All of these aspects are considered critical
      causes for the development of cervix and uterine cancer. The results demonstrated
      that the scholar degree, the age in which the patients started sexual activity,
      the number of sexual partners, the number of births, the age in which the first
      birth occurred, and the smoking habits are facts that influence the natural
      evolution of this disease and should be considered as important background.

PMID- 12793019
TI  - [Evaluation of the bone mass in the different types of menopause ].
AB  - OBJECTIVE: To evaluate the bone mass condition in the different types of
      menopause and know if there is difference between the groups. DESIGN: Case
      reports. MATERIAL AND METHODS: From September through November 2001 at the
      Specialties Hospital No. 1, we studied 184 patients with menopause. They were
      divided in 5 groups: 74 regular menopause, 31 surgical menopause and oophorectomy
      unilateral, 43 surgical menopause and bilateral oophorectomy, 32 premature
      menopause, and 4 post-radiotherapy menopause, analyzing the bone mass with a
      densitometry. The statistical analysis was by descriptive statistics and t
      student to find the difference between the groups. RESULTS: We observed 45% with
      osteopenia y 8% with osteoporosis in regular menopause. In surgical menopause and
      oophorectomy unilateral group, we found 26% with osteopenia and 6% with
      osteoporosis. There were 42% with ostepenia and 14% with osteopososis in surgical
      menopause and bilateral oophorectomy group. In premature menopause, we found 47%
      with osteopenia and 12% with osteoporosis. In post-radiotherapy menopause, we
      found 75% with osteopenia and 25% with osteoporosis. All of them with
      predominance in femur. We did not observe any significant difference between the
      surgical and the premature menopause groups. CONCLUSIONS: In a half of patients
      with menopause we found bone mass decrease with predominance in femur, like
      osteopenia. There was no significant difference between the surgical and the
      premature menopause groups.

PMID- 12793020
TI  - [Anemia among rural pregnant women living at 540 meters above sea level].
AB  - OBJECTIVE: To assess the prevalence of anemia among rural pregnant women living
      at 540 meters above sea level in Colima, Mexico. MATERIAL AND METHOD: A cross
      sectional studied was carried out, we included women attending antenatal clinic
      between January 1996 and December 2000, who are not receiving prenatal iron and
      folato supplements previously. Blood samples were examined for hemoglobin (Hb)
      concentration. Information on date of examination, name, private residence, age,
      gestational age, marital status, educational status, work, menarche, parity,
      cesarean sections, miscarriages, intergestation lapse, and hemoglobin levels was
      recorded. The information was confirmed by visit at private residence. Altitude
      was derived from official maps. Our measures to diagnose anemia were gestational
      age and low hemoglobin concentration. Three groups were integrated with the
      following criterions: GROUP I: Gestational age 1st to 5th week, Hb less than 12.0
      g/dL. GROUP II: Gestational age 6th to 15th week, Hb less than 11.0 g/dL. GROUP
      III: Gestational age 16th to 40th week, Hb less than 10.4 g/dL. We calculated
      percentages, frequencies, and prevalence. RESULTS: We found 35 women, 25.7%
      showed anemia, the higher Hb concentration was of 14.6 g/dL and the lower was of
      9 g/dL. CONCLUSIONS: The prevalence of anemia was of 0 x 1000 women in-group I,
      117 x 1000 women in-group II, and 437 x 1000 women in-group III.

PMID- 12793021
TI  - [Emergency cerclage:10 years experience at the ABC Hospital].
AB  - OBJECTIVE: To evaluate the success of emergency cerclage procedures and neonatal
      outcome at the ABC Hospital. MATERIAL AND METHODS: A retrospective analysis
      between January 1, 1991 and December 31, 2000 was carried out. Gestational age at
      the time of the procedure was recorded, as well as the average time in
      gestational weeks after the procedure, maternal complications and neonatal
      outcome. RESULTS: Seven patients were included with dilatation of the internal
      cervical of 3 cm o more and membranes protruding to the vagina in all cases.
      Patients with uterine activity, a cerclage procedure in a previous pregnancy, and
      corioamnioitis were excluded. The average gestational age for the procedure was
      23.3 weeks. The average length of duration of the current pregnancy after the
      procedure was 5.4 weeks; with 58.3% of live newborns recorded. CONCLUSIONS: The
      emergency cerclage procedure continues to be a heroic attempt to continue the
      pregnancy. By the results published in the literature, it can be stated that the
      prolongation of pregnancy is highly variable with neonatal survival rate between
      12-73%.

PMID- 12793022
TI  - [Presacral neurectomy and uterine nerve ablation in chronic pelvic pain.
      Laparoscopic management. A comparative study].
AB  - Chronic pelvic pain is a difficult handling medical and surgical condition and of
      transcendent importance to women who suffer from it. This condition has been
      associated to different diseases as endometriosis, adenomiosis, adnexal mass,
      pelvic inflammatory disease, pelvic adhesive disease. The present study was
      carried out comparing two laparoscopic surgical methods in an randomized way;
      laparoscopic uterine nerve ablation and a presacral neurectomy, with 12 patients
      in each group and a follow up of 12 mont. Results demonstrate a similar
      resolution on both groups in the short term and a significant difference on
      pain's resolution within the presacral neurectomy group in the long term without
      post-surgery or trans-surgery complications. Concluding the presacral neurectomy
      is a safe and dependable method that allows a high success rate on chronic pelvic
      pain patients.

PMID- 12793023
TI  - [Early post-partum discharge : systematic review of the literature].
AB  - BACKGROUND: Hospital stays after vaginal delivery and cesarean birth have
      shortened over the past 30 years, that practice have contributed to the
      controversy about the safety of this policy for mother and infants. OBJECTIVE: To
      carry out a systematic review of the literature to determine the actual evidence
      of the effect of early post-partum and post-cesarean discharge on maternal and
      neonatal readmissions, breast feeding, maternal satisfaction with medical care
      and post-partum depression. METHODOLOGY: We included all randomized controlled
      trials that evaluate different institutional policies evaluating early vs.
      prolonged length of post-partum hospitalization in low risk patients with vaginal
      or cesarean delivery, with full-term newborns, weighting more or equal 2,500 g.
      The methodology of the studies was evaluated with the Cochrane Handbook criteria.
      RESULTS: We included five randomized clinical trials, but they have
      methodological flaws. These include selection bias, limited power and exclusions
      of patients after randomization. We initially planned to perform a formal meta
      analysis of this randomized controlled trials, but the methodological limitations
      prevent aggregation and quantification in a meta-analysis. CONCLUSIONS: The
      existing evidence in randomized controlled trials is insufficient to judge the
      safety of early post-partum discharge. Published reports concluded showing that
      this practice is safety, had a limited significance.

PMID- 12793024
TI  - [Gynecological sequela of puerperal infections. 1948].
AB  - This paper is part of a symposium on puer petal infections that was presented in
      the 7th., Asamblea Nacional de Cirujanos. The authors review the factor and
      evolution and the final results in puerperal infections. (1 degree Classification
      of the pathogenic germ, 2 degrees Site of infection, 3 degrees Effect of the
      pregnancy on the genital organs, 4 degrees Means of invasion, 5 degrees Organic
      resistance). A final review is made considering the above mentioned factor in the
      gynecological pathology to which puerperal sepsis can lead, presenting synoptic
      charts. Finally, the gynecological processes due to the surgical treatment of the
      puerperal infection in relation to sterility and psychic disturbances such as
      frigidity ad dyspaurenia are reviewed.

PMID- 12793025
TI  - New health care challenges for the "old Europe".

PMID- 12793026
TI  - [Research emphasis on geriatric preventative medicine].

PMID- 12793027
TI  - [Vaccination against Alzheimer disease?].

PMID- 12793028
TI  - [Electroconvulsive therapy as maintenance therapy and for prevention of
      recurrence in psychiatric disorders and Parkinson disease].
AB  - Electroconvulsive therapy is a reliable and safe option for patients with
      psychiatric disorders who are resistant or intolerant to medication as these
      patients usually respond quickly to this form of treatment. For clinicians, the
      management of these often severely ill patients is an important challenge given
      the high rate of relapse of these disorders. Maintenance electroconvulsive
      therapy is an interesting treatment option for these patients. Until now, only
      few controlled studies exist about the long-term outcome of this treatment in
      depressive disorders and other psychiatric disorders. Altogether, this form of
      outpatient prophylactic therapy has been found to be safe, well tolerated, and
      efficacious in relapse prevention. Moreover, it has been found to reduce
      hospitalization rates. Particularly in the elderly, and in patients who have been
      shown to be refractory to medication regimens, maintenance electroconvulsive
      therapy should be seriously considered as a means to reduce the risk of
      recurrence of illness. In Parkinson's disease maintenance electroconvulsive
      therapy is not widely established although its usefulness has been documented in
      numerous studies. First-line evidence data on incidence, dimensions and outcome
      of cognitive side effects under maintenance electroconvulsive therapy is still
      warranted.

PMID- 12793029
TI  - Osteoprotegerin serum levels in women: correlation with age, bone mass, bone
      turnover and fracture status.
AB  - Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast
      function and therefore plays an important role in bone remodelling. This study
      aimed to evaluate the clinical value of serum OPG. Do higher OPG serum levels
      reflect decreased bone resorption and perhaps higher bone mass in women? Serum
      OPG levels were measured in 177 healthy women (aged 17-85 years) and in 48
      untreated patients (mean age 71 +/- 5) with established osteoporosis, and related
      to age, bone mass, markers of bone turnover and, in the case of patients with
      osteoporosis, to pre-existing vertebral fractures. In healthy women OPG levels
      showed a positive correlation with age (r = 0.25, p < 0.001) but not to bone mass
      or markers of bone turnover. In women with osteoporosis, however, there was a
      strong relationship between serum OPG and markers of bone turnover (serum c
      terminal crosslinked telopeptides of thpe I collagen (sCTX): r = +0.82, p <
      0.0001; osteocalcin (OC): r = +0.69, p < 0.0001), with patients who had higher
      levels of bone-turnover markers showing higher serum levels of OPG. After
      adjustment for bone mass and bone markers, patients with pre-existing vertebral
      fractures had significantly lower serum OPG levels than patients without
      fractures (57 +/- 8 vs. 97 +/- 10 pg/ml, [mean +/- SE], p < 0.01). The age
      dependent increase of OPG as an antiresorptive factor may reflect an insufficient
      paracrine mechanism of bone cells to compensate for bone loss in older age. In
      patients with osteoporosis, however, OPG correlated strongly with markers of bone
      turnover; this may point toward a higher level of RANKL/OPG expression in these
      patients. Finally, low OPG serum levels seem to be associated with vertebral
      fractures. We hypothesise that low OPG levels in preset conditions of bone
      turnover may indicate a higher risk of fracture in patients with osteoporosis.

PMID- 12793030
TI  - Appointments at a thyroid outpatient clinic and the lunar cycle.
AB  - INTRODUCTION: Several variables of health-related human behaviour have been
      analysed with regard to a possible association with lunar phases. The aim of this
      study was to evaluate a possible relation between the lunar cycle and the number
      of requests for appointments at an outpatient clinic. This variable has not been
      studied hitherto. METHODS: We analysed a total number of 11,413 requests for
      appointments at our thyroid outpatient clinic during one year. Access to this
      clinic is not restricted, and all patients with known or suspected thyroid
      disease living in the area of Vienna may ask for an appointment. During the study
      period, 8,852 patients requested a follow-up appointment, and 2561 patients asked
      for a new appointment. We analysed a possible cyclic pattern in these requests
      using a nonlinear regression model based on both groups of patients. RESULTS: A
      cosinus curve with a period of 29.531 days (the mean length of a lunar cycle) was
      significantly associated with the number of requests for both follow-up
      appointments (p = 0.007) and new appointments (p = 0.001). Requests for follow-up
      appointments had their highest peaks three days after the full moon, whereas
      requests for new appointments were most frequent five days afterwards.
      CONCLUSION: Our findings suggest that lunar phases may affect patients' requests
      for appointments at a thyroid outpatient clinic. To the best of our knowledge,
      this is the first study reporting a possible association between health-related
      behaviour and lunar phases using requests for appointments as a relevant
      variable. There is a need for more research into the mechanism underpinning this
      behaviour.

PMID- 12793032
TI  - Subcutaneous granuloma annulare in an adult.
AB  - A 38-year-old female presented with a history of recurrent multiple deep dermal
      nodules located on the dorsa of the feet, over the ankle joints and lower
      pretibial area. Laboratory investigation excluded rheumatoid arthritis.
      Histopathological examination showed changes in the deep dermis: histiocytes in
      palisades around foci consisting of degenerated bundles of collagen, mucin,
      fibrin and "nuclear dust". The diagnosis of subcutaneous granuloma annulare was
      made on the basis of the clinical and histological features. Treatment with
      dapsone was successful, and in the course of two months the nodules disappeared.

PMID- 12793031
TI  - Predictive role of serum procollagen III peptide and Knodell's index in survival
      prognosis of patients with hepatitis B virus liver cirrhosis.
AB  - OBJECTIVE: The objective of the study was to improve the accuracy of survival
      prognosis in patients with liver cirrhosis using procollagen III peptide (PIIIP),
      as a marker of inflammation and fibrogenesis, and Knodell's histologic activity
      index (KI) in addition to previously used prognostic factors. PATIENTS AND
      METHODS: Five-year survival was followed in a group of 75 patients with hepatitis
      B virus (HBV) liver cirrhosis (patients testing anti-HBe positive and HBV-DNA
      negative). There were 31 patients with compensated cirrhosis and 44 with
      decompensated cirrhosis. The diagnostic procedure included clinical, laboratory,
      ultrasound and pathohistologic examination. We combined PIIIP and KI with other
      significant variables to achieve the highest possible sensitivity, specificity
      and accuracy for survival prognosis in HBV liver cirrhosis. The models were
      compared using ROC analysis. RESULTS: At the end of the five-year period of
      survival follow-up, there were 39 survivors and 36 patients had died (only three
      died from an extrahepatic cause). In the quantitative model, the discriminant
      canonical function (DCF) identified PIIIP, bilirubin, prothrombin time, ascites
      and KI as statistically significant parameters in the prognosis of five-year
      survival. Calculation of the score based on DCF yielded an accuracy of 89.3%. In
      the semiquantitative model, the analysis of variance identified PIIIP, bilirubin,
      albumin, pro-thrombin time, alkaline phosphatase, ascites and KI as significant
      variables. When PIIIP was added to the clinicohistologic diagnosis, Child-Pugh
      score and KI, the level of accuracy improved by 12% (from 78% to 90%), 11% (from
      79% to 90%) and 10.6% (from 80% to 90.6%), respectively. When calculated with the
      three biochemical parameters (alkaline phosphatase, PIIIP and bilirubin) and KI
      identified by DCF, the accuracy was 90.6%. CONCLUSION: Combining PIIIP and KI
      with other prognostic parameters is useful in achieving a better precision of
      survival prognosis in patients with HBV liver cirrhosis.

PMID- 12793033
TI  - [Methicillin resistant Staphylococcus aureus (MRSA) infection in a dog in the
      Netherlands].
AB  - In the Netherlands, methicillin resistant Staphylococcus aureus (MRSA) are
      regularly isolated from humans. We present the first isolation of MRSA from
      animal origin in the Netherlands. A coagulase positive staphylococcus was
      cultured from an infected wound in a Dutch dog that recently underwent surgery
      abroad. The staphylococcus was resistant to methicillin, ampicillin, amoxycillin
      + clavulanic acid, cephalexin, erythromycin, lincomycin, tetracycline, gentamicin
      and enrofloxacin. It was identified as S. aureus by fermentation of mannitol and
      Martineau-PCR. The presence of mecA was confirmed by PCR.

PMID- 12793034
TI  - [Domitor not to used in collies?].

PMID- 12793035
TI  - [I could have invented the polder model! Interview by L.C.T. Verkleij].

PMID- 12793036
TI  - [Leishmaniasis].

PMID- 12793037
TI  - [Experimental animals: where are the veterinarians? Professionalization of the
      veterinarian working with experimental animals].

PMID- 12793038
TI  - [Homeopathy, a remarkable treatment].

PMID- 12793039
TI  - [Secretarial rights of the Society Against Home Remedies].

PMID- 12793040
TI  - [A humane kit for the cat].

PMID- 12793041
TI  - [Off-label use and the 'explanation'].

PMID- 12793042
TI  - [Is adenosine used effectively in clinical practice?].

PMID- 12793043
TI  - [Biorhythms].

PMID- 12793044
TI  - [von Willebrand disease type 2N (Normandy)].

PMID- 12793045
TI  - [High or low dose, that is the question?].

PMID- 12793046
TI  - [Bacterial infections in patients with acute hemorrhage due to portal
      hypertension--personal experience].
AB  - Acute haemorrhage from the upper gastrointestinal tract is a frequent and serious
      complication which affects 20-60% patients with cirrhosis of the liver and portal
      hypertension. It is assumed that bacterial infections can be the direct cause of
      haemorrhage but accurate data on the influence of infection on the development
      and course of haemorrhage are lacking. Acute haemorrhage as a result of portal
      hypertension has a very high mortality, 30-50%, and an early relapse of
      haemorrhage occurs in as many as 40% of these patients. Most recent meta-analyses
      indicate that bacterial infection is an independent prognostic factor in failure
      of haemostasis and has a significant impact on the mortality of these patients.
      The authors examined for the presence of bacterial infection (blood, urine,
      throat, ascites) 25 patients with cirrhosis of the liver and acute haemorrhage as
      a result of portal hypertension and compared the results with a group of 25
      patients with cirrhosis of the liver and portal hypertension without acute
      haemorrhage. According to the results in patients with acute haemorrhage due to
      portal hypertension there is a significantly higher incidence of bacterial
      infections than in patients with cirrhosis of the liver and portal hypertension
      without acute haemorrhage. The results confirm the necessity to administer
      antibiotic prophylaxis to cirrhotic patients with varicose bleeding, not only to
      patients with symptoms and evidence of infection but also in their absence.
      Antibiotic prophylaxis extends the survival period of these patients.

PMID- 12793047
TI  - [Ambulatory monitoring of blood pressure in regular dialysis therapy].
AB  - Ambulatory monitoring of the blood pressure (AMBP) makes it possible to diagnose
      in hypertensive patients the so-called dipper phenomenon, i.e. a drop of the BP
      during the night provided that the patient is asleep. The absence of this
      phenomenon implies as a rule serious damage of the cardiovascular apparatus,
      brain or kidneys. By means of an apparatus ABP monitoring type 90207 of Space
      Labs. Inc. a group of 16 patients in regular dialysis treatment (RDT) was
      examined and the blood pressures were evaluated before and after dialysis.
      Patients with the dipper profile reacted more adequately during dialysis i.e. by
      a drop of the blood pressure due to the loss of excessive fluid which they
      retained during the interdialysis period, as compared with the group with a non
      dipper profile which may be exposed to a greater risk of cardiovascular
      complications. The authors conclude that detection of the absence of the non
      dipper phenomenon can reveal risk patients. AMBP can explain so-called
      paradoxical hypertension at the end of haemodialysis despite major removal of
      fluids by ultrafiltration, and that moxonidine participates in a significant way
      in the elimination of the non-dipper phenomenon.

PMID- 12793048
TI  - [Effectiveness and safety of adenosine in the therapy and diagnosis of
      arrhythmias].
AB  - Adenosine is a drug with unique clinical and electrophysiological properties.
      Despite this, its use in Slovakia is rare. The decisive reason, besides its
      price, is the physicians fear of potential adverse effects and their limited
      knowledge regarding its clinical use. This study was aimed at analysis of the
      contribution of adenosine to the treatment and diagnostics of arrhythmias and
      evaluation of its safety. We studied the effect of adenosine in 62 patients.
      Adenosine terminated paroxysmal supraventricular tachycardia (PSVT) in 16 of 44
      patients (36.4%) and in another 21 patients (47.7%) we revealed the type of
      unclear PSVT. We observed contribution to the diagnostics of wide QRS complex
      tachycardia in 3 of 6 patients (50.0%). Latent ventricular preexcitation was
      induced in 2 of 12 patients (16.7%). Subjective complaints after adenosine were
      frequent (at least 1 symptom in 80.6% patients), but all of them were of short
      duration and clinically not significant. We did not observe any relevant
      complication of adenosine. The average maximal RR interval after adenosine was
      1.75 sec. We consider adenosine in adequately indicated patients with respect for
      its contraindications as highly effective drug in the treatment and diagnostics
      of specific arrhythmias.

PMID- 12793049
TI  - [Dynamic stress echocardiography in asymptomatic patients treated for malignant
      diseases in childhood].
AB  - INTRODUCTION: The authors used echocardiography at rest and dynamic stress
      echocardiography to assess left ventricular function in asymptomatic patients
      treated during childhood or adolescence by chemotherapy containing
      anthracyclines. MATERIAL AND METHODS: 137 patients were examined (81 men, 56
      women) aged 16.6 +/- 4.8 years (median 17 years) where at the age of 9.1 +/- 4.8
      years (median 9 years) malignant disease was detected and treatment with a
      cumulative dose of anthracyclines 242 +/- 110 mg/m2 (median 240 mg/m2) was
      administered. The control group was formed by 30 subjects (14 men, 16 women) aged
      19.5 +/- 5.2 years (median 20 years). The echocardiographic examination was made
      at rest and immediately after a dynamic stress on an ergometer with a load of 25
      W/2 mins. RESULTS: In 8% patients (n = 11) a reduction of the fractional
      shortening (FS) LV < 30% was found. The values of the ejection fraction (EF), the
      median shortening of the circumferential fibre and endosystolic wall stress,
      excursion and thickening of the posterior wall of the LV were significantly worse
      as compared with the group with fractional shortening > or = 30% and the control
      group. The maximum drop of EF was to 40% and of FS to 20%. The values of the
      index of the global LV function (according to Teie) were as compared with the
      control group worse in both sub-groups of patients. No differences were found in
      the exercise tolerance between groups. Values of the ejection fraction at rest
      and after a exercise were in the sub-group with FS < 30% significantly lower as
      compared with the others. The values of the stress increment of EF were elevated
      in all sub-groups. In none of the subjects the load caused a decline of the EF.
      CONCLUSIONS: Chemotherapy with anthracyclines leads to a late disorder of several
      indicators of left ventricular function. Asymptomatic patients with a drop of the
      EF value to 40% or FS to 20% preserve their load tolerance and contraction
      reserve of the left ventricle. The finding of a preserved contraction reserve and
      good exercise tolerance implies a more favourable prognosis of the patient.
      Echocardiography at rest should be made repeatedly after treatment, in case of a
      pathological finding a loading test must be indicated to evaluate the contraction
      reserve and its possible development.

PMID- 12793050
TI  - [Combined training in patients with systolic left ventricular dysfunction].
AB  - The objective of the work was to evaluate the effect of eight-week combined
      training on the performance, aerobic capacity and basic haemodynamic parameters
      in patients with systolic dysfunction of the left ventricle and to assess its
      safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/-
      11.1 years with coronarographically verified chronic ischaemic heart disease and
      with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before
      the beginning and after completion of the rehabilitation programme (eight weeks)
      a spiroergometric examination was made, up to the symptom-limited maximum.
      Fitness elements were included after 2 weeks of aerobic training. The lesson
      lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer
      with an intensity of the load at the level of the anaerobic threshold (20 mins.),
      the stage of fitness training on a combined training machine (20 mins) and the
      relaxation stage (10 mins). In the fitness stage the patients started to exercise
      at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum)
      The results showed after eight-week combined training a significant (p < 0.05)
      increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in
      patients with systolic left ventricular dysfunction. There was a significant
      increase in the capacity of the transport system expressed by the value of the
      maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from
      5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood
      pressure at rest, systolic and diastolic, and of the baseline value of the heart
      rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not
      significant.

PMID- 12793051
TI  - [Long-term treatment with statins in patients with ischemic heart disease after
      coronary angioplasty].
AB  - Long-term statin therapy is the corner-stone in management of patients with
      coronary artery disease. PURPOSE OF STUDY: The aim of our study was to analyze
      the state of the statin therapy at patients undergoing percutaneous coronary
      intervention (PCI) and to determine predictors of long-term statin treatment.
      METHODS: We performed a retrospective study in 520 patients who underwent
      percutaneous coronary angioplasty in 2nd Dept. of Internal Medicine, 1st School
      of Medicine, Charles University, Prague during the year 2000. Data were collected
      from hospital records and from a mailed questionnaire. RESULTS: The response rate
      was 61.9% and the average response time was 11.6 +/- 3.5 months after PCI. Long
      term statin therapy was prescribed in 52.5%. In patients with
      hypercholesterolemia 67.1% were treated in comparison with 32.3% treated patients
      without this diagnosis (p < 0.0001). Patients aged 70 years and older were
      treated significantly less frequently then younger individuals (30.6% vs. 61.3%,
      p < 0.0001). Patients with a history of prior revascularization procedure were
      treated significantly more often then patients undergoing the first procedure
      (64.8% vs. 49.8%, p < 0.05). Multivariate logistic regression analysis was
      applied to detect significant predictors of long-term statin therapy. Only
      hypercholesterolemia and statin prescription at discharge were identified as
      independent positive predictors, whereas age > or = 70 years and male gender had
      negative predictive value. CONCLUSION: By course of evidence-based medicine,
      patients who underwent PCI in our study are undertreated by statins. Statin
      treatment should be initiated in all patients treated by PCI with increased
      cardiovascular risk. Patients at defined risk for undertreatment are mainly older
      patients and men. The prescription of statin therapy at the time of hospital
      discharge appears to be a very effective tool to improve long-term statin
      therapy.

PMID- 12793052
TI  - [NO (nitric oxide) and its significance in regulation of vascular homeostasis].
AB  - The endothelium is the largest autocrine and endocrine organ of the human
      organism. It participates in the regulation of the blood flow and tonus of the
      vascular wall, activation of thrombocytes, adhesion of monocytes to the vascular
      wall, thrombogenesis, lipid metabolism and growth of vessels. Endothelial cells
      may produce some 25 different biologically active substances. The most important
      one among them is probably NO. Under physiological conditions endothelial cells
      release permanently a small amount of NO or EDRF (endothelium-derived relaxing
      factor) and participate thus in the regulation of the tonus of the vascular wall
      at rest. The presence of NO excreated by endothelial cells can be detected in all
      parts of the circulation, from large arteries to small capillaries. Increased NO
      excretion is caused by a number of physiological stimuli, e.g. a rise of the
      blood pressure, drop of the partial oxygen pressure or the action of
      acetylcholine, ADP, ATP, thrombin, bradykinin or histamine. NO is a chemical
      messenger which is formed during oxidation of L-arginine to L-citrullin by the
      action of the enzyme NO synthase (NOS). Endothelial NOS is described as eNOS
      (endothelial/Type III/NOS-3). There exist also two other different isoforms of
      this enzyme: nNOS (neuronal/Type I/NOS-1/bNOS) andiNOS (inducible/Type II/NOS-2.
      NO plays an important part on the regulation of vascular homeostasis. It has a
      number of potential antiatherogenic functions. It causes vascular vasodilatation.

PMID- 12793053
TI  - [Circadian rhythms in cardiovascular diseases--arrhythmias].
AB  - Circadian patterns have been observed for variety of cardiovascular disorders,
      including cardiac arrhythmias, sudden cardiac death, cerebrovascular events,
      episodes of stable angina, unstable angina and acute myocardial infarction. The
      morning predominance of these events has been well documented in a number of
      large population studies. This fact provides the stimulus for better
      understanding our own chronobiology and the periodicity of circadian rhythms
      which contribute to this predominance of adverse events in the morning hours. We
      now understand that a number of important physiological parameters such as heart
      rate, blood pressure, vascular reactivity, cardiac contractility, and various
      hemostatic factors all demonstrate a circadian pattern similar to that described
      for cardiovascular disorders. Several recent studies have also emphasize the
      importance of changes in posture, time of awakening, physical activity, mental
      stress as potential triggers. Circadian patterns have been observed for several
      supraventricular arrhythmias, premature ventricular beats, ventricular
      tachycardias including sudden cardiac death. The chronobiological therapeutic
      systems can help to prevent life threatening events.

PMID- 12793054
TI  - [Circadian rhythms in cardiovascular diseases--ischemic heart disease].
AB  - Several key advances in understanding of pathophysiology now provide the
      opportunity to develop improved treatment and prevention strategies. First, the
      importance o mechanism of plaque rupture and thrombosis in onset of myocardial
      infarction. Second, there has been demonstrated, that plaques that lead to acute
      occlusion often have only a mild degree of stenosis. A third advance that has
      stimulated the field has been the recognition that time of onset of cardiac
      events is not random but instead shows a circadian pattern of onset. In the
      decade since the 1985 observation by Muller a spol. that the frequency of onset
      of myocardial infarction peaks at 9 a.m., numerous publications have supported
      this observation not only for myocardial infarction, but also for sudden cardiac
      death, transient myocardial ischemia, and stroke. Refinement of these
      epidemiological observations has led, first, to the conclusion that the morning
      peak in disease onset is due in part to the physical and mental stressors
      associated with morning awakening and activity and, second, that stressors such
      as heavy physical activity and anger can trigger acute cardiovascular events.

PMID- 12793055
TI  - [Use of chronobiology findings in therapy of cardiovascular diseases].
AB  - The concept of homeostasis in biology postulates that there is constancy of the
      intern milieu. Thus is assumed the risk and exacerbation of disease are
      invariable and independent of the time of day, day of month, and month of year as
      are the responses of patients to diagnostic tests and medications. Findings from
      the field of chronobiology, the study of biological rhythms, challenge the
      concept of homeostasis and the many assumptions and procedures of clinical
      medicine based on it. It is now recognized that human functions have daily,
      weekly, monthly and yearly biological rhythms. Plants, animals, and insects also
      have chronobiological rhythms. Circadian patterns have been observed for variety
      of cardiovascular disorders, including cardiac arrhythmias, sudden cardiac death,
      cerebrovascular events, episodes of stable angina, unstable angina and acute
      myocardial infarction. The morning predominance of these events has been well
      documented in a number of large population studies. It is now recognized that
      circadian and other rhythms of the gastrointestinal tract and vital organs are
      capable of significantly affecting the pharmacokinetics and dynamics of
      cardiovascular and other medications. This means that the effects of therapeutic
      interventions administered in identical doses in the morning versus the evening
      may not be equivalent. The prevention and treatment of cardiovascular disease
      must take into account chronobiological factors.

PMID- 12793056
TI  - [Standards for diagnosis and therapy of diabetic retinopathy and its
      complications. Recommendations of the Czech Diabetology Society and the Czech
      Ophthalmology Society].

PMID- 12793057
TI  - [Von Willebrand disease--type 2N (case report)].
AB  - Isolated reduced coagulation activity of FVIII may be a manifestation of
      haemophilia A, carriership of haemophilia A, haemophilia A in a woman, acquired
      haemophilia A and type 2N of von Willebrand's disease. The authors were concerned
      with the cause of isolated reduction of the coagulation activity of factor VIII
      (19 IU/dl) in a 40-year-old woman with a history of excessive haemorrhage of the
      type of mild haemophilia A with a negative family history. The personal history,
      family history and laboratory examination suggested type (variant) 2N of von
      Willebrand's disease. For indirect evidence the authors used a therapeutic study
      where they investigated the effect of administration of a concentrate of
      coagulation factors VIII/von Willebrand's factor (1/2), 28 IU factor VIII/kg body
      weight, on the coagulation activity of factor VIII. They recorded a half-life
      prolonged to 53 hours as compared with controls where the half-life was less than
      12 hours. The therapeutic study confirmed sufficient coagulation activity of
      factor VIII, the utilization of which improved as a result of administration of
      von Willebrand's factor. This investigation confirmed indirectly as the cause of
      reduced coagulation activity of factor VIII in the examined patient the assumed
      type (variant) 2N of von Willebrand's disease.

PMID- 12793058
TI  - [Administration of maximal or median doses of drugs in cardiovascular diseases?].
AB  - In recent years some specialists recommend to treat patients with cardiovascular
      diseases with maximal doses of drugs and refer to the results of extensive
      clinical studies. On critical evaluation of some it seems that the results are
      not interpreted accurately and that the highest doses of drugs (or combined
      treatment) do not produce better results than the use of smaller doses. This
      applies e.g. to the study HOT with felodipine in hypertensive patients and
      patients with cardiac insufficiency in the ATLAS study with lisinopril and the
      MERIT-HF study with metoprolol. It applies also the HOPE study with ramipril in
      secondary prevention in subjects with cardiovascular diseases. Efforts to achieve
      as low as possible lipid values has also some pitfalls. The author recommends to
      treat comprehensively all patients and to select maximal doses only in selected
      subjects.

PMID- 12793059
TI  - [History of nephrology and extracorporeal drug removal at the L. Pasteur Hospital
      in Kosice].
AB  - The authors describe the development of clinical nephrology from 1948 to 2002 at
      the Medical Faculty of the P. J. Safarik University and L. Pasteur Faculty
      Hospital from the aspect of therapeutic and preventive care, teaching and
      research activities. The dialysis centre which was established in 1966 at the
      Medical Clinic of the Faculty Hospital in Kosice continued in the activities as
      the Nephrological laboratory which was founded in 1954. This laboratory still
      operates under the conditions of the Nephrological Clinic. In 1964 at the Medical
      Clinic the first percutaneous renal biopsy was implemented. In 1966 the first
      peritoneal dialysis was implemented and the first haemodialysis in a patient with
      chronic renal failure, later gradually all so far known therapeutic methods were
      introduced which replace renal function and are used in acute and chronic renal
      failure and in acute intoxication. On March 18, 1977 in the authors' department
      the first haemoperfusion over active charcoal was made successfully in a patient
      intoxicated with parquat. It was the first haemoperfusion in the former
      Czechoslovak Republic. From 1991 at the Clinic a Sub-chair of nephrology and
      dialysis was established attached to the Institute for Postgraduate Training,
      later SPAM. Within the framework of the latter several nephrological courses were
      organized as well as courses in extracorporeal elimination treatment and in acute
      toxicology. The department acted also as a training place for future
      nephrologists before the specialization examination in nephrology. Since 1981
      successfully several research grants concerned with the use of haemoperfusion
      over active charcoal and other sorbents in acute intoxications were completed as
      well as grants focused on metabolic vitamin disorders in chronic renal failure.
      On October 24 1997 in our department within the framework of the P. J. Safarik
      University Medical Faculty and L. Pasteur Faculty Hospital the Nephrological
      Clinic was established, the first one in the Slovak Republic. This stimulated
      further qualitative development of nephrology not only in Kosice but in the whole
      of Slovakia.

PMID- 12793060
TI  - [Pathophysiology solves key questions in the therapy of type 2 diabetes
      mellitus].
AB  - Pathophysiological mechanisms accompanying Type 2 diabetes mellitus are the
      basement for the rational therapy of this disease. The finding of the
      relationship between impaired insulin secretion and its action including the
      regulatory mechanisms is of importance for successful treatment. In a review
      article there are included the most important pathways influencing therapeutical
      considerations in clinical practice.

PMID- 12793061
TI  - [Drug therapy of portal hypertension].
AB  - The author presents a list of preparations used to influence portal hypertension
      resulting from cirrhosis of the liver, in particular in treatment or prevention
      of haemorrhage from oesophageal varices or gastropathy. The author describes the
      mechanism of action of drugs administered in acute haemorrhage (vasopressin,
      terlipressin, somatostatin, octreotide)) and preparations used in primary or
      secondary prevention of this haemorrhage (beta-blockers, nitrates, newly tested
      preparations or combinations). In the conclusion are recommendations for
      practical procedures according to principles of evidence-based medicine.

PMID- 12793062
TI  - [Management of dementia and cognitive functions in patients after cerebrovascular
      stroke: new results from the PROGRESS study].

PMID- 12793064
TI  - Radionuclide bone scan in initial staging of breast cancer.
AB  - Radionuclide bone scans of 100 patients with newly diagnosed breast cancer were
      retrospectively analysed. The number and topography of increased area of uptake
      were noted. Diagnosis criterion was defined by at least four foci of increased
      uptake, outside peripheral articular joints. In case of a number between one and
      three, the result was considered doubtful and radionuclide bone scan was
      confronted to available standard X Rays or/and radionuclide bone scan follow-up.
      Correlations of radionuclide bone scans with T, N and the clinical stage were
      assessed using chi-square methods. Metastases were present in 9 patients (9%). In
      five of these cases, the pattern was manifestly metastatic without the need to
      other investigation. In the other cases, interpretation required complementary
      investigation. The yield of metastases was very low in localized stages, this
      pointed out the difficulty in interpretation of radionuclide bone scans for
      localized stages, probably due to a less skeletal extension.

PMID- 12793063
TI  - [Graves' ophthalmopathy: diagnosis and highlights on etiopathogenesis and
      treatment].
AB  - It's due to extraocular tissues enlargement: extraocular muscles. Thyroid
      stimulating receptor antibodies were first incriminated. However, Graves'
      proptosis can appear several months or years before development of goiter or
      thyrotoxicosis. Different treatment are possible: glucocorticoids, radiotherapy,
      surgical orbitary decompression, classical surgery. Treatment of hyperthyroidism
      has to be undertaken similarly. Classically, surgical or medical treatment with
      antithyroid drugs were indicated.

PMID- 12793065
TI  - [Epidemiologic profile of sexually transmitted diseases (STD) through a
      specialized consultation of STD].
AB  - INTRODUCTION: A confidential, free and specialised consultation of sexually
      transmitted diseases (STD) was initiated since 1993 in the department of
      Dermatology of hospital Charles Nicolle. We present the epidemiological and
      clinical features of this consultation. PATIENTS AND METHODS: It is a
      retrospective study including patients consulting during a period of 7 years
      (1993-1999). 546 patients were included. The mean age of our patients was 29
      years and the sex-ratio 9. The diagnosis of urethritis was done for 242 patients.
      This diagnosis was clinic in the most cases. Urethral swabs was done for 71
      patients. Neisseria gonorrhoeae was isolated in 56 cases and Chlamydia
      trachomatis in 15 cases. 41 patients were directed to our consultation for a
      positive syphilis serology. Condyloma were diagnosed in 23 cases and scabies in
      12 cases. HIV serology was positive in 10 cases. In 3 cases, the diagnosis of HIV
      infection was done in this consultation. DISCUSSION: The epidemiologic profile
      showed a frequency of young men, bachelors and having multiple sexual partners.
      Clinically, urethritis was the principal STD observed.

PMID- 12793066
TI  - [Antibiotic sensitivity of Streptococcus pneumoniae in Tunisia: results of a
      multicenter study (1998-1999)].
AB  - We report the results of a multicenter tunisian study, performed over a two-year
      period (1998-1999), to determine the susceptibility pattern of Streptococcus
      pneumoniae in our country. A total of 146 S. pneumoniae were collected during the
      study period. 76 were recovered from adults and 70 from children. 53% of isolates
      have decreased susceptibility to penicillin, 24% with low level resistance, and
      11% with high level resistance. Amoxicillin and cefotaxime decreased
      susceptibility rates were: 12% (low level resistance exclusively). and 14% (10%
      with low level resistance and 4% with high level resistance) respectively.
      Strains isolated from children, showed higher resistance to b lactams than those
      isolated from adults. Resistance rates to other antibiotics were as follow:
      erythromycin 28%, choramphenicol 14%, cyclins 23%, thrimethoprim-sulfamethoxazole
      28% and rifampin 1%. No vancomycin resistant strain was found. The acquire
      resistance rates of Streptococcus pneumoniae in Tunisia are worrying, essentially
      for penicillin and erythomycin. Amoxicillin and cefotaxime have conserved a good
      activity.

PMID- 12793067
TI  - [Chronic myeloid leukemia. What's in the future therapy in Black Africa?].

PMID- 12793068
TI  - [Delivery by forceps: indications and materno-fetal morbidity].
AB  - A retrospective study concerning patients having had a delivery by means pair of
      forceps over a period going from 1st Jun 1999 to 31st December 2000. The
      frequency of the use of forceps for delivery is 4.95%. The defect of eviction was
      an indication of the pair of forceps. Fetal suffering was the main indication.
      Maternal morbidity was represented essentially by a more or less injury of the
      genital tract with a rate of 11.1%. The rate of neonatal mortality is 1.28%. The
      maternal improvement of the maternal and fetal prognosis depends on an accurate
      indication of the use of forceps. In certain circumstances, mainly in fetal
      suffering, it is often difficult to choose between the high way and the low way.

PMID- 12793069
TI  - [Characterization of HIV-1 subtypes in Sfax, Tunisia].
AB  - We studied HIV-1 subtypes in 20 patients, originating from Tunisia in 18 cases
      and Libya in 2 other cases and seen in Regional Hospital of Sfax during 1993
      1997. Among the 18 tunisian patients, 14 are infected by subtype B. Nine of them
      are living in european countries and were probably infected by intravenous drug
      and/or sexual route. The five other patients infected by subtype B correspond to
      autochtonous cases: 3 patients were infected by their partner, 1 was infected by
      blood transfusion and the last one has had multiple sexual partners. For another
      tunisian patient, serum cross-reacted with 2 peptides C and B (C/B) corresponding
      to coinfection or subtype recombination. Two strains were indeterminate by SSEIA.
      The last tunisian patient, contaminated in Libya, is infected by a strain
      presenting cross-reactivity with subtype A and C (A/C). This same strain was
      found in one libyan patient. The second libyan patient is infected by subtype C.
      CONCLUSION: In Tunisia, we noted the frequency of HIV-1 subtype B, originating
      from european countries. But, the fear of other HIV-1 subtypes introduction and
      therefore, the emergency of new recombinants must incite us to a greatest
      vigilance in survey of HIV-1 infection.

PMID- 12793070
TI  - [Involved factors in stability of children's asthma. A study of 150 children in
      Mahdia].
AB  - In order to reduce the mortality and morbidity by asthma in perpetual increasing,
      taking in charge of asthmatic child must be general (therapeutic and educative)
      with the intention to stabilize il cause of the lack of curing ait. The aim of
      our work was to determinate the factors in stability of asthma. Our study was
      retrospective, inducing 150 asthmatic children regularly observed since at least
      6 months and more than 4 years old: 77 of them was judged stable and 73 unstable.
      Stable asthma concerned insignificatively children who are more than 8 year old,
      from urban areas, unexposed to tobacco living is sunny homes and when there is no
      associated factors like effort asthma and gastro-oesophagien reflux. Instability
      of asthma has been in significantly correlated with the initial severity and non
      adaption to treatment.

PMID- 12793071
TI  - [Immunological study in sickle cell disease patients: importance of the
      complement system].
AB  - Ten Tunisian patients, with homozygote sickle cell disease and asplenia were
      studied to investigate and to determine possible immunological function defects.
      Obtained results directed us to an abnormality of the alternate complement
      pathway activation which is expressed by a decreased hemolytic activity, while
      the classic pathway is normal. Quantification of C3, C4, C5, C6, C7 and factor B
      by immunochemical assay were normal, whereas factor B functional activity was
      depressed to a mean level of about half of normal in eight patients, IgG was
      increased in one subject and IgA in two others. Numeration of Band T cells
      revealed slight decrease in proportion of CD3 and CD4 at one patient associated
      with an increase in B cells, but normal or increased absolute numbers of all
      cells population.

PMID- 12793072
TI  - [Prevalence of Helicobacter pylori infection in normal or asymptomatic patients].
AB  - The propose of this prospective study was to assess the prevalence of
      Helicobacter pylori infection in asymptomatic subjects in year 2000. Ninety eight
      patients not suffering from upper gastrointestinal symptoms were enrolled in this
      study. The mean age was 39 years. Helicobacter pylori was present in 81 patients
      (82.7%). Helicobacter pylori infection increase with age. It was maximal between
      30 and 50 years. Helicobacter pylori prevalence is still high in Tunisia as well
      as in most developing countries. Improvement of hygiene conditions will decrease
      this prevalence.

PMID- 12793073
TI  - [Primary hemochromatosis induced diabetes mellitus in 8 Black Africans in
      Yaounde, Cameroon].
AB  - We analysing 8 cases of diabetes secondary to primary hemochromatosis in a group
      of black diabetic patients in Yaounde. Diagnosis of primary hemochromatosis is
      based on clinical and biological arguments. Central hypogonadism is associated to
      diabetes in 75%, dilated cardiomyopathy existed in 37.5%, arthropathy in 75%.
      Diabetes is mostly type II. CONCLUSION: Secondary diabetes to primary
      hemochromatosis does exist in Black Africa. Diagnosis should be in the mind of
      clinician when in a diabetic patients are associated: central hypogonadism,
      dilated cardiomyopathy and chronic arthropathy. In the future diagnosis of
      hemochromatosis will be easier by genetic because of recent discovery of the gene
      of the disease.

PMID- 12793074
TI  - [Single coronary artery. A case report].
AB  - The authors report the case of a patient undergoing coronary angiography for an
      inferior myocardial infarction related with atherosclerosic lesions but
      associated with a rare anomalous origin of all three coronary arteries from
      single ostia in the left sinus of valsalva.

PMID- 12793075
TI  - [Idiopathic thrombopenic purpura and pregnancy].
AB  - The idiopathic thrombocytopenic purpura (ITP) associated to a pregnancy is a
      frequent eventuality, and this association have a high risk. The mother platelet
      numeration cannot predict the fetal affection, only the mother antiplatelet
      antibodies rate have a predictive value. The obstetrical attitude is highly
      discussed and is conditioned by the fetus platelet rate. If the corticotherapy
      brings an improvement of the maternal and fetal platelet rate, the gammaglobulin
      therapeutic interest will be confirmed. Thanks to a ITP case associated to
      pregnancy and a literature review, we will try to appreciate this disease for a
      pregnant woman, evaluate its consequences on the pregnancy and approach the
      different steps of the taking care actions.

PMID- 12793076
TI  - [Urinary calcium oxalate supersaturation beyond nephrolithiasis. Relationship
      with tubulointerstitial damage].
AB  - A number of studies have demonstrated that the urinary ion activity product (IAP)
      of calcium oxalate (CaOx), as an index of urinary CaOx supersaturation (SS), is
      higher in renal stone formers than in normal subjects. Besides, the relation
      between CaOx SS and lithogenesis, crystal CaOx exposition can produce tubular
      cell as well as renal interstitial lesions. The aim of our study was to evaluate
      the possible relationship between CaOx SS and tubulointerstitial (TI) damage in
      an animal model of hyperoxaluria. During four weeks, male Sprague-Dawley rats
      received: G1 (n = 8) control regular water, and G2 (n = 8) 1% ethylene glycol
      (ETG) (precursor for oxalates) in drinking water. In order to evaluate urinary
      CaOx SS, IAP assessed by Tisselius formula was performed. At the end of the
      study, renal lesions were evaluated by light microscopy and immunohistochemistry.
      Animals from G2 (ETG) presented higher (p < 0.01) values of: a) urinary oxalate
      excretion; b) urinary CaOx SS; c) crystalluria score; d) proteinuria; and lower
      (p < 0.01) creatinine clearance, with respect to the control group (G1).
      Moreover, pathology studies showed that rats from G2 (ETG), presented significant
      TI lesions characterized by a higher (p < 0.01) score of: a) tubular atrophy;
      inflammatory infiltrates (monocyte/macrophage); c) crystal deposits; d)
      intersticial fibrosis; e) interstitial alpha-smooth muscle actin; f) collagen
      type III; g) TI TGF beta 1 compared with G1 (control). Rats from G2 (ETG)
      presented a high correlation between urinary CaOx SS and most of the TI damage
      parameters evaluated, in especial with interstitial fibrosis. Both, inflammatory
      infiltrates and urinary CaOx SS were the most significant variables related to
      interstitial fibrosis. Finally, since hyperoxaluric animals showed higher urinary
      CaOx SS associated with higher renal TI damage, the results from this study
      suggest the presence of a tight link between urinary CaOx SS and renal TI damage.
      Considering these findings we think that urinary CaOx SS control rises in
      importance beyond nephrolithiasis.

PMID- 12793077
TI  - [Pregnancy of 18 women survivors of childhood cancer].
AB  - To analyze the effect of cancer treatment on pregnancy, delivery and progeny of
      women survivors of childhood cancer, 18 of them (15 to 49 years of age) were
      interviewed, with diagnosis and treatment between july 1965 and December 1982 (15
      from the Oncology Unit of the Children's Hospital of Buenos Aires and 3 from a
      private practice) and evaluated until December 2000. The following potential
      determinants to suffer adverse effects on pregnancy, delivery and descendence
      were considered: laparotomy, alkylating agents, doxorubicine, infradiaphragmatic
      radiotherapy. Diagnoses were: non-Hodgkin lymphoma 6, nephroblastoma 5,
      retinoblastoma 3, osteosarcoma 1, fibrosarcoma 1, Langerhans cell histiocytosis
      2. Ten patients were laparotomized, 11 were treated with alkylating agents, 8
      with doxorubicin and 7 with infradiaphragmatic radiotherapy. Twenty-eight
      offsprings were born. Congenital anomalies were not detected. Inherited cancer
      was observed in two siblings whose mother had suffered bilateral retinoblastoma.
      Additional follow-up from woman survivors of childhood cancer is necessary to
      determine the effect of cancer and its treatment on pregnancy, delivery and
      offspring.

PMID- 12793078
TI  - [Physician-patient relationship, scientific medicine and alternative therapies].
AB  - The objective of this paper is to describe the magnitude and characteristics of
      the use of complementary therapies in clinical practice. A consecutive sample of
      540 outpatients who had sought medical care for the first time at the General
      Internal Medicine Program of a University Hospital were interviewed. A
      questionnaire was completed, collecting socio-demographic informations, data on
      physical and psychological health, perception of physician-patient relationship,
      self-medication, and beliefs associated with the disease and its treatment.
      Lifetime prevalence use of alternative therapies was near 55%. The most used were
      homeopathy and herbal medicines (40.8% and 37.6%, respectively). The evaluation
      of these practices was considered "excellent/very good/and good" 84.5% of the
      time. Significant associations were: females (p < 0.00001), high level of
      education (p < 0.001), dissatisfaction with the way in which the cause of the
      disease had been investigated and how the diagnosis and treatment had been
      communicated (p < 0.03), psychological and psychiatric treatment (p < 0.00001),
      self-medication (p < 0.0002), pain and concern during over 6 months due to
      disease or disability (p < 0.00001), lack of confidence in scientific medicine (p
      < 0.00001), the belief that "spiritual problems" (p < 0.00001), "mental
      conditions" (p < 0.003), and "emotional conditions" (p < 0.00001), popular
      beliefs, particularly dano & envidia (p < 0.00001), and mal de ojo (p < 0.001)
      have triggered the disease. One third of the patients attended the hospital while
      undergoing an alternative therapy that may pose an interference or interaction
      hazard. Emphasis is placed on the importance of medical education to assess
      physician-patient relationship and the ability to convey trust in medical
      procedures and treatments, and scientific consulting for other practices.

PMID- 12793079
TI  - Effect of the definition of hypopnea on apnea/hypopnea index.
AB  - The objective of this study was to determine whether different decreases in
      oxygen saturation (SaO2) or the presence of electroencephalographic arousals
      (EEGA) in the definition of hypopnea modify hypopnea index and apnea/hypopnea
      index and the prevalence of obstructive sleep apnea/hypopnea syndrome (OSAHS). A
      total of 20 polysomnographies performed in patients with OSAHS were analyzed.
      There are four different definitions of hypopnea: > or = 30% reduction in airflow
      or 50% decrease in abdominal movement associated with decreases SaO2 > or = 3%
      (type 1); decreases SaO2 > or = 3% or EEGA (type 2); decreases SaO2 > or = 4%
      (type 3); decreases SaO2 > or = 4% or EEGA (type 4). The prevalence of OSAHS was
      calculated for an apnea/hypopnea index (AHI) > or = 10 and > or = 15. Hypopnea
      index (HI) and AHI types 2 and 4 were higher than type 3 (HI: type 2: 20 +/-
      10.6, type 4: 18.6 +/- 10, type 3: 11.4 +/- 10, p < 0.001; AHI: type 2: 23.3 +/-
      11.6, type 4: 21.4 +/- 11.2, type 3: 14.7 +/- 11.6, p < 0.001). No differences
      were observed between HI and AHI types 1 and 2 (HI: type 1: 17.4 +/- 10, type 2:
      20 +/- 10.6; AHI: type 1: 20.6 +/- 11.8, type 2: 23 +/- 11.6, p > 0.05). The
      prevalence of OSAHS was 30-55% in type 3, 70-85% in type 4 (p < 0.05), and 70-85%
      in types 1 and 2 (p > 0.05). In our patient's population, the presence of EEGA in
      the definition of hypopnea significantly increased the HI, the AHI and the
      prevalence of OSAHS when associated with a > or = 4% decrease in SaO2.

PMID- 12793080
TI  - [Seroprevalence of Chagas disease in 17 rural communities of "Monte
      Impenetrable", Chaco Province].
AB  - In the month of July 1999 and 2000 we studied the presence of Trypanosoma cruzi
      antibodies in residents of 17 isolated rural communities of "Monte Impenetrable",
      in Chaco Province. This area has 3,000 km2 inhabited by about 3,000 person and
      presents all the conditions for the development of Chagas disease. A total of 344
      blood samples were analysed for Chagas disease. All samples, stored with SEROKIT,
      were tested with indirect hemagglutination test, enzyme-linked immunosorbent
      assay and particle agglutination test. Samples reactive for two assays were
      considered positive. Serological evidence of human T. cruzi infection was
      demonstrated in 183 (53.50%) out of 344 individuals. In the 1-15 years age group
      the percentage of positivity was 45.83% and in the 1-5 years age group 53.85%. a)
      General infection prevalence in these rural communities was 7 times higher than
      the national average estimated rate (7.20%). b) Prevalence in the 1-15 years age
      group was 25 times higher in relation to that found in residents of rural areas
      under entomology vigilance (1.77%). c) The prevalence in younger than five years
      old indicated the absence of vectorial control. The Tobas communities presented
      higher prevalence than Criollos, although the risk factors to acquire the disease
      were similar in both populational groups. These findings show the urgency of
      public health policies and sanitary decisions, specially in these zones of the
      country.

PMID- 12793081
TI  - Von Willebrand factor cleaving protease activity in the physiopathology of
      microangiopathic disorders.
AB  - The von Willebrand factor cleaving protease (VWFCP) modulates the von Willebrand
      factor (VWF) multimeric size in normal plasma. VWFCP activity levels are
      decreased in different physiological and pathologic situations. Different
      techniques have been developed to unfold the purified VWF (perfusion at high
      shear rate, dialysis against urea in nitrocellulose filters), to detect the VWFCP
      activity on it (multimeric analysis of VWF, collagen binding to VWF assay) and to
      use the patient plasma both as the source of the enzyme and substrate. In this
      paper we compared the above mentioned methods with new ones: normal plasma
      dialyzed on membranes instead of purified VWF, dialysis of the samples against
      urea in tubing instead of nitrocellulose filters, and sonicated plasma to remove
      the endogenous VWF. The perfusion assay and detection by multimeric analysis
      showed a limit of detection (25%) of VWFCP activity. Dialysis against urea in
      both supports and detection by multimeric analysis, showed a better limit of
      detection (3%), but the recovery of the samples was not as efficient in
      nitrocellulose filters as it was in tubing. The detection by collagen binding to
      VWF has more advantages because it allows to analyze more samples than the
      multimeric analysis does in the same assay. The dialysis of plasma by membranes
      to obtain the source of exogenous VWF requires no complex equipment. The method,
      which uses patient plasma as the source of the enzyme and substrate, was
      inapplicable in our experience because the values could not be interpolated in
      the reference curve.

PMID- 12793082
TI  - [Yawning and temporal lobe epilepsy].
AB  - Temporal lobe epilepsy is a partial epileptic disorder in which mesial structures
      are responsible for the principal ictal symptoms. Its characteristic feature is
      the recurrence of simple and complex partial seizures, associated with postictal
      confusion and amnesia of the event. The facilitating effect of NREM sleep on the
      propagation of the seizure, as well as the sleep abnormalities provoked by
      epilepsy were evident in our two patients. Yawning is a physiological reflex
      induced by arousal and drowsiness and may appear in different neurological
      conditions. Its relation with epilepsy of limbic origin has been rarely reported.
      We describe in a 95 year old male patient, the occurrence of yawning followed by
      complex partial seizure during a state of drowsiness. His EEG showed independent
      bilateral interictal foci of temporal sharp waves and after being medicated with
      carbamazepine 400 mg/day, the episode did not recur. Another patient, a 17 year
      old female, displayed complex partial seizures and secondarily generalized
      seizures with yawning during the posictal period, after naps. The EEG was normal
      and her polysomnography showed bilateral synchronous temporal spikes and slow
      waves with secondarily generalization during stage 2 of NREM sleep that produce
      paroxysmal microarousals and increased stages 1 and 2 of NREM sleep and REM sleep
      diminished. After being medicated with divalproex sodium 750 mg/day, she suffered
      no further seizures. Temporal lobe epilepsy, sleep-wake cycles and yawning seem
      not only to share the same anatomic structures but also the same neurochemical
      mechanisms. The fact that endogenous opiods are considered as part of a
      protective system that stop and prevent seizures may allow us to postulate that
      yawning would be the expression of the endogenous opiods induced mechanisms that
      stop and prevent the recurrence of the temporal lobe epilepsy. Another hypothesis
      may be that this is only a particular form of temporal lobe epilepsy.

PMID- 12793084
TI  - [Acute necrotizing myelitis in an AIDS patient].
AB  - In the setting of HIV infection, cytomegalovirus (CMV) and herpes simplex virus
      type 1-2 (HSV 1-2) can affect both the central and peripheral nervous systems.
      These agents can involve the spinal cord and produce a necrotizing transverse
      myelitis. This usually occurs in AIDS patients with severe immunodeficiency: CD4+
      lymphocyte counts typically are less than 50 cell/microL. The clinical
      presentation, CSF and imaging studies can provide a high level of suspicion
      diagnosis. Prompt initiation of antiviral specific drugs is essential. We report
      a patient with an acute necrotizing myelitis (cauda equina syndrome) secondary to
      CMV and HSV infections.

PMID- 12793083
TI  - [Effect of hydroxyurea on hemoglobin S].
AB  - Previous studies have determined the laboratory alterations, clinical efficacy
      and toxicity profile associated with hydroxyurea (HU) therapy in patients with
      severe sickle cell anemia. We report the efficacy of HU treatment in the
      prevention of vaso-occlusive crises in an 11-years-old boy with severe sickle
      cell disease. The number of vaso-occlusive crises, hospital days and blood
      transfusions in the year before HU treatment were compared with the same
      parameters at 6, 12, 24, 36 and 72 months of treatment. A decrease in the
      frequency of vaso-occlusive crises, blood transfusions and days spent in hospital
      were demonstrated during the HU treatment period compared to the same period
      before hand. The clinical and laboratory response to HU was dramatic in this
      severely affected patient, allowing him a normal schooling and social life. The
      adverse effects observed were not serious and reversed after transient
      discontinuation of HU. We conclude that long-term chronic treatment with HU for
      seriously ill sickle cell patients appears feasible, and devoid of any major
      toxicity.

PMID- 12793085
TI  - [New mechanisms involved in the pathogenesis of pituitary adenomas].
AB  - We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably
      transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein
      4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice,
      but had showed a late increase in tumor size. We found that they had lost in vivo
      the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP
      4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas,
      but not in other human pituitary adenomas or normal pituitary. In addition ICI
      182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17 beta
      estradiol in combination had an additive effect on GH3 cell proliferation. Their
      action was inhibited by blocking BMP-4 with ICI 182,780 or 17 beta-estradiol with
      Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4
      physically interacts with the ER alpha/ER beta. We show for the first time the
      role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP
      4/E2.

PMID- 12793086
TI  - [Recurrent pleural effusion and hepatic nodules].

PMID- 12793087
TI  - [Gas exchange in acute respiratory distress syndrome].
AB  - The hypoxemia of acute respiratory distress syndrome (ARDS) depends chiefly upon
      shunt and ventilation-perfusion (VA/Q) inequality produced by fluid located in
      the interstitial space, alveolar collapse and flooding. Variables other tham
      inspired oxygen fraction and the underlying physiological abnormality can
      influence arterial oxygen partial pressure (PaO2). Changes in cardiac output,
      hemoglobin concentration, oxygen consumption and alcalosis can cause changes in
      PaO2 through their influence on mixed venous PO2. Gas exchange (GE) in ARDS may
      be studied using the inert gas elimination technique (MIGET) which enables to
      define the distribution of ventilation and perfusion without necessarily altering
      the FIO2 differentiating shunt from lung units with low VA/Q ratios and dead
      space from lung units with high VA/Q ratios. Different ventilatory strategies
      that increase mean airway pressure (positive end-expiratory pressure, high tidal
      volumes, inverse inspiratory-expiratory ratio, etc) improve PaO2 through
      increasing lung volume by recruiting new open alveoli and spreading the intra
      alveolar fluid over a large surface area. Also prone-position ventilation would
      result in a marked improvement in GE enhancing dorsal lung ventilation by the
      effects on the gravitional distribution of pleural pressure and the reduction in
      the positive pleural pressure that develops in dorsal regions in ARDS. Inhaled
      nitric oxide (NO) has been shown to increase PaO2 in ARDS patients by inducing
      vasodilation predominantly in ventilated areas redistributing pulmonary blood
      flow away from nonventilated toward ventilated areas of the lung thus resulting
      in a shunt reduction. On the same way inhaled prostaglandins (PGI2 or PGE1)
      causes selective pulmonary vasodilation improving pulmonary GE. Intravenous
      almitrine, a selective pulmonary vasoconstrictor, has been shown to increase PaO2
      by increasing hypoxic pulmonary vasoconstriction. A synergistic effect was found
      between inhaled NO and almitrine. In spite of the improval of GE shown by these
      different techniques on ARDS, no effect was demonstrated on mortality or duration
      of mechanical ventilation.

PMID- 12793088
TI  - [Calcimimetic agents in the treatment of hyperparathyroidism secondary to chronic
      renal failure].
AB  - The recent discovery and cloning of the extra cellular calcium sensing receptor
      (CaSR) has allowed a better understanding of the regulation of normal calcium
      metabolism and of rare disturbances in mineral metabolism. In the parathyroid
      glands the CaSR is responsible for modulating parathyroid hormone release as a
      function of the extra cellular calcium level. This discovery has allowed the
      development of drugs that mimics or potentiates the actions of extra cellular
      calcium on the CaSR, called calcimimetics that decrease parathyroid hormone
      secretion without increasing serum calcium. The new calcimimetics are small
      organic molecules that act as allosteric activators of the CaSR and they are in
      their initial face of clinical development. Although the experience with these
      drugs is limited, they have shown to effectively lower parathyroid hormone levels
      in patients with hyperparathyroidism secondary to end-stage renal failure without
      inducing important side-effects. Thus calcimimetic compounds have considerable
      potential as new drugs for the treatment of secondary hyperparathyroidism and
      uremic bone disease.

PMID- 12793089
TI  - [New clinical indicators. Health-related quality of life].
AB  - In the last decades the need of better measurements of health outcomes has
      increased the interest for new clinical indicators. Health-related quality of
      life (HRQoL) has emerged in this context as a multidimensional model approach
      where the patient is the exclusive source of information. The main objective of
      HRQoL measurement is to provide a global evaluation of the impact of diseases and
      the consequences of treatments over the daily life of the patients. The
      instruments developed for that purpose are questionnaires; either generic--for
      the comparison between different diseases-, or specific--aimed to evaluate
      particular conditions. These questionnaires must demonstrate several psychometric
      properties, such as reliability, validity, responsiveness, and for some authors
      also feasibility. In many areas, HRQoL studies have demonstrated to increase the
      knowledge of the natural history of diseases and its global consequences, beyond
      the classic health outcomes information based on morbidity and mortality rates.
      This knowledge may assist in the design of epidemiological studies and improve
      the comparison of strategies in therapeutic interventions. Nevertheless, some
      controversial issues remain such as the clinical implications of absolute scores
      obtained, and the need for updating the content of the instruments in accordance
      with the changes in natural history of diseases under evaluation.

PMID- 12793091
TI  - [Chronology of the discovery of HIV as the cause of AIDS].

PMID- 12793090
TI  - [Nobel Prize for Medicine 2002: Brenner, Horvitz, Sulston and the Caenorhabditis
      elegans worm].

PMID- 12793092
TI  - [Medicine and publicity].

PMID- 12793093
TI  - [Certification of physicians in Internal Medicine].

PMID- 12793094
TI  - [Early defibrillation in the treatment of sudden cardiac arrest].
AB  - Recovery from nontraumatic cardiac arrest depends on the presence of all the
      elements in the chain of survival. "Early defibrillation" is critical because
      ventricular fibrillation is the most common initial dysrhythmia of sudden cardiac
      arrest. Defibrillation is the only treatment, and survival from ventricular
      fibrillation is determined by time. Out-of-hospital studies have demonstrated
      that defibrillation provided by first responders improves survival. Technologic
      advances have simplified defibrillation delivery through the development of
      automated external defibrillators (AEDs). Early defibrillation programs with AEDs
      are quickly becoming a standard of care for emergency medical service systems
      throughout the United States. Improvement in in-hospital survival rates from
      cardiac arrest is not as evident as in the emergency medical service community.
      Medical centers need to assess response times to cardiac arrest and implement AED
      programs. All the nurses should learn to use an AED as part of basic life support
      training.

PMID- 12793095
TI  - [New pathogenetic mechanisms of idiopathic dilated cardiomyopathy: changes in
      coronary microcirculation].
AB  - There is growing evidence of the presence and relevance of coronary microvascular
      abnormalities in many cardiac diseases. In particular, it has been recently shown
      that dilated cardiomyopathy is characterized by coronary microvascular
      dysfunction since its early onset. Abnormal coronary microcirculatory function is
      not an effect of myocardial damage but in turn seems to be able to cause
      progressive contractile dysfunction, ventricular dilatation and heart failure.
      The mechanisms are largely unknown but both myocardial hypoperfusion and
      myocardial ischaemia are most probably involved. It has been demonstrated that in
      patients with dilated cardiomyopathy the presence of severe coronary
      microcirculatory dysfunction is an independent and relevant prognostic factor.
      From these studies it is more and more evident that coronary microvascular
      dysfunction is a new pathogenetic mechanism in dilated cardiomyopathy and that
      the coronary microcirculation should be considered a new target of treatment in
      cardiac diseases at risk to evolve towards heart failure.

PMID- 12793096
TI  - [High-risk hypertension].
AB  - Arterial hypertension is the main risk factor for cardiovascular diseases in
      western countries and its prevalence, currently around 25% in the general
      population, is on the rise. Prevention and treatment of high blood pressure and
      its acute and chronic complications represent a public health priority, due to
      the relevance of its economic and social consequences. Unfortunately, recent
      epidemiological surveys indicate that too many patients are either unaware of
      their condition or are not receiving adequate treatment, in spite of the
      availability of a large armamentarium of antihypertensive agents which, when used
      in proper combination, enables the physician to lower blood pressure in virtually
      all patients. Perhaps more importantly, today it is possible to identify, among
      the large number of hypertensive patients, those at higher absolute risk for
      complications. To this end, beside considering the severity of blood pressure
      load, one should always accurately evaluate the presence of other risk factors
      and subclinical end-organ damage at the cardiovascular and renal level. This
      approach is useful in tailoring treatment to each patients' characteristics and
      leads to the optimisation of its cost/benefit ratio.

PMID- 12793097
TI  - [Atrial fibrillation as a complication of colorectal tumors].
AB  - We undertook a study to provide a quantitative basis to the clinical observation
      of an unexpected high frequency of atrial fibrillation in patients with
      colorectal cancer. In our study we considered a total of 1463 patients admitted
      during a period of 12 years (1987-1998) to the Department of Surgery of our
      Hospital for surgical treatment of colorectal cancer (case group: mean age 66
      years) or non-neoplastic diseases including inguinal hernia, cholelithiasis,
      varicose veins and hemorrhoids (control group: mean age 65.6 years). We found a
      three times higher likelihood of having atrial fibrillation in patients with
      first diagnosis of colorectal cancer compared to controls. Logistic analysis was
      used to exclude an effect of age. Our study suggests that atrial fibrillation
      could be considered a non metastatic effect of colorectal cancer. Several
      pathophysiological mechanisms could explain this observation. A recent study,
      which reports a significant elevation of C-reactive protein in patients with
      atrial fibrillation, suggests that this arrhythmia could be promoted by a
      systemic inflammatory state. In conclusion, atrial fibrillation could be
      considered a pathological condition not only dependent to organic heart diseases;
      further studies are needed to evaluate the real impact of systemic inflammatory
      state or other non-cardiovascular diseases on the excess of mortality in the
      patients with atrial fibrillation.

PMID- 12793098
TI  - [Myocardial infarction in the course of antiretroviral therapy with protease
      inhibitor].
AB  - The use of protease inhibitors (PIs) in the antiretroviral therapy (ART) of HIV-1
      infection has reduced the rate of morbidity and mortality; but, unfortunately,
      this therapy has several side effects and a long term toxicity. Unexpected lipid
      abnormalities and cardiovascular complications are observed. We report a case of
      myocardial infarction in a young man HIV-1 positive patient without a history of
      metabolic disorders and cardiovascular pathologies undergoing PI treatment. The
      new ART without PI was not suppressive, while hypertriglyceridemia value improved
      by omega 3 fatty acids use. Our opinion is to continue ART with PI and to correct
      lipid abnormalities with the use of antidislipidemic drugs instead to change a
      demonstrated suppressive ART.

PMID- 12793099
TI  - [Cardiac complications of anorexia nervosa].
AB  - The death rate of anorexia nervosa (AN) patients is up to 30 times greater than
      that of age-matched normal women. Bradycardia, hypotension and mitral valve
      prolapse are cardiac abnormalities that can be frequently found in AN patients.
      Risk of death is substantially linked to QT prolongation, which could be due to
      hypokalemia (binge/purging type AN) or to a starvation-derived anatomical
      remodelling of the heart (restricting type AN). The principal risk factors are
      duration of illness > 10 years, chronic hypokalemia, plasmatic albumin
      chronically < 3.6 g/dl and absolute QT > or = 600 ms.

PMID- 12793100
TI  - [Diagnosis of neurogenic syncope--current views].
AB  - Neurocardiogenic syncope is a very common clinical problem and represents the
      most frequent cause of syncope. Its diagnosis is difficult because there are
      several and heterogeneous causes of syncope, that can interact each other, and
      the accuracy of the available diagnostic instruments is sometimes not high
      enough. For these reasons, the classification of a syncope as neurocardiogenic is
      the result of an evaluation, whose main purpose is the exclusion of the other
      possible causes of syncope with worse prognosis. The head tilt-up test is
      recommended for the diagnosis of the most frequent type of neurocardiogenic
      syncope, the vasovagal syncope. The methodological improvement of tilt test
      could, in the future, improve its diagnostic accuracy and could optimise the time
      of execution.

PMID- 12793101
TI  - Injuries to preschool children and infection control practices in childcare
      programs.
AB  - Injuries represent the leading cause of death for children aged 0 to 12 years,
      and exposure to blood or bodily fluids at the time of injury may pose a health
      and safety problem. More than 800,000 injuries were reported in 2000, and many
      occurred in childcare programs. This survey examined rate, type, and extent of
      injuries in centers and the infection control practices employed by staff.
      Participants included 131 children aged six weeks to seven years, enrolled in two
      childcare programs in an urban setting. Eight hundred ninety-seven injury reports
      with 1,023 (126 simultaneous) injuries were recorded over a one-year period.
      Results indicated the majority of injuries (39%) were for bites and 11% were self
      inflicted. Injuries were classified as minor (99%) or moderate (1%) with 73%
      receiving first aid by staff. Bleeding from injuries was minimal in 14% of
      injuries, while no injuries reported moderate or severe bleeding. The rate of
      medically attended (first aid treatment) injury was 5.31 per 100,000 child hours.
      Injury rates decreased with age in the center (P = .001), were higher for males
      (P = .036), and occurred most frequently in the morning (P = .001). Age, gender,
      and time of the day were significant predictors of injuries in the multivariate
      model.

PMID- 12793102
TI  - The nature and extent of bullying at school.
AB  - In elementary schools, the prevalence of bullying ranges from 11.3% in Finland to
      49.8% in Ireland. The only United States study of elementary students found that
      19% were bullied. Bullying behavior declines as students progress through the
      grades. School bullying is associated with numerous physical, mental, and social
      detriments. A relationship also exists between student bullying behavior and
      school issues such as academic achievement, school bonding, and absenteeism.
      Prevention of school bullying should become a priority issue for schools. The
      most effective methods of bullying reduction involve a whole school approach.
      This method includes assessing the problem, planning school conference days,
      providing better supervision at recess, forming a bullying prevention
      coordinating group, encouraging parent-teacher meetings, establishing classroom
      rules against bullying, holding classroom meetings about bullying, requiring
      talks with the bullies and victims, and scheduling talks with the parents of
      involved students. Finally, this review suggests further studies needed to help
      ameliorate the bullying problem in US schools.

PMID- 12793103
TI  - The principles of effectiveness: early awareness and plans for implementation in
      a national sample of public schools and their districts.
AB  - The US Department of Education's Principles of Effectiveness require recipients
      of Safe and Drug-Free Schools and Community Act funds to: a) base drug and
      violence prevention programs on needs assessment data, b) develop measurable
      program goals and objectives, c) implement programs with research evidence of
      effectiveness, and d) periodically evaluate programs relative to their goals and
      objectives. This paper reports the extent of awareness of the Principles of
      Effectiveness and plans for their implementation among public school districts
      and schools in the United States in the year following their announcement.
      Results showed a greater percentage of public school districts than individual
      schools knew about the principles and planned for implementation, but baseline
      levels of awareness for both districts and schools were relatively low. Schools
      were more likely to know about the principles when their associated school
      district also knew. Results suggest a need for greater communication about the
      principles to school districts, and in turn, a need for greater communication
      between district and school-level substance use prevention staff.

PMID- 12793104
TI  - Do school-based health centers provide adequate asthma care?
AB  - School-based health centers (SBHCs) are increasingly charged with providing
      primary care services including asthma care. This study assessed SBHC provider
      adherence to the National Heart, Lung, and Blood Institute (NHLBI) asthma care
      guidelines and the association among provider adherence, patient characteristics,
      and asthma outcomes. A cross-sectional study design was used to assess SBHC chart
      data from 415 children with asthma attending four inner-city elementary schools
      (K-5) in the Bronx, NY. Asthma symptoms, peak flow use, follow-up visits, and
      referrals to asthma specialists were documented in the charts of 60%, 51%, 22%,
      and 3% of subjects, respectively. Thirty-three percent of charts had SBHC
      clinician-documented severity classifications, of which 70% had appropriate
      medications prescribed. Asthma education and an asthma plan were documented in
      18% and 10% of charts, respectively. Environmental triggers and tobacco exposures
      were documented in 71% and 49% of charts, respectively. Older children (> 8
      years) were more likely to have documentation of peak flow use for asthma
      management, asthma education, follow-up visits, and written asthma plans, whereas
      younger children (< 8 years) were more likely to miss more days of school (all p
      < .05). Overall, provider adherence to NHLBI guidelines was inadequate, with
      adherence somewhat better for older children.

PMID- 12793105
TI  - Gender differences in the consequences of a coercive sexual experience among
      adolescents attending alternative schools.
AB  - Of 490 middle and high school students attending alternative schools who
      participated in this study, 18.2% of females and 6.7% of males reported a past
      unwanted sexual experience. Relative to nonabused subjects, female and male
      adolescents who reported a forced sexual experience were more likely to exhibit
      externalizing problems such as sexual risk behaviors and internalizing problems
      such as depression and suicidal thoughts in the past two weeks. Females with a
      history of a coercive sexual experience also had increased odds of drug and
      alcohol use, and violence-related behaviors. The magnitude of these associations
      ranged from a twofold increase to a tenfold increase. Controlling for ethnicity,
      family income, and family support had less impact on the strength of associations
      between a forced sexual experience and sexual risk behaviors for females than for
      males. A forced sexual experience remained significantly associated with
      depression for females and suicidal thoughts for males. Alcohol use in the past
      30 days was the only substance use-related problem that remained significant for
      females. Violence-related behaviors did not remain significant in the presence of
      control variables for females. Interventions focusing on adolescents with a
      history of a coercive sexual experience in general, and in alternative schools in
      particular, are suggested by these results. More research focusing on the
      differential impact of a coercive sexual experience on males and females is
      crucial.

PMID- 12793106
TI  - Correlates of sexual experience among a nationally representative sample of
      alternative high school students.
AB  - Little is known about risk and protective factors associated with sexual
      experience among alternative school students that might prove useful in targeting
      and guiding early interventions to prevent onset of sexual risk behavior.
      Researchers analyzed data from the national Alternative High School Youth Risk
      Behavior Survey. Principal components analysis identified six risk and protective
      factors: weapon carrying; tobacco use; cocaine, inhalant, and needle use; alcohol
      and marijuana use; participation in sports; and fighting. Composite variables
      with significant bivariate relationships to sexual experience, as well as
      demographic variables, were entered into a logistic regression analysis to
      determine independent effects of these correlates on students' sexual experience
      (N = 6.037). Nearly 90% of students reported having sexual intercourse. In
      multivariate analysis, significant demographic correlates of sexual experience
      included female gender (58% more likely than males to report ever having sex),
      African American race (2.83 times more likely than non-Hispanic Whites), and age
      (28% more likely with each advancing year). Attending school in a rural or
      suburban region corresponded to a 31% decrease and 46% decrease, respectively, in
      the odds of ever having sex. Weapon carrying, and cocaine, inhalant, and needle
      use, were associated with a 35% and 46% increase, respectively, in the odds of
      ever having sex. Students reporting they had ever used alcohol or marijuana, and
      those reporting recent fighting behavior, were 2.7 and 1.6 times more likely,
      respectively, to report sexual experience. Most alternative school students have
      had sexual intercourse, with those students engaging in substance use, weapon
      carrying, and fighting behaviors being at greater risk for sexual experience.
      Prevention programs for high-risk youth attending alternative high schools need
      to consider how to promote continued abstinence among the small but important
      minority of alternative school students not yet sexually experienced.

PMID- 12793107
TI  - Using an Internet-based registry to link school immunization records with
      community records.

PMID- 12793108
TI  - [The anatomy of episodic memory: evolution of concepts].
AB  - Historically, the hippocampus belongs to the limbic lobe described by Broca or to
      the Papez circuit. His role was first restricted to emotions. The observations
      that medial temporal lobe (MTL) damage led also to mnemonic dysfunction have been
      advanced greatly by the study of brain-damaged patients and experimental animals
      studies. Functional imaging, either positron emission tomography or functional
      MRI, has helped to change this historical concepts. Recent findings have
      converged on the observation that hippocampal or parahippocampal regions could be
      consistently activated in verbal or visuospatial memory paradigms. Furthermore,
      these functional neuroimaging studies have also stressed the importance of the
      prefrontal cortical activations in such memory processes. These results show that
      memory is subserved by a more widely distributed cortical network than expected.

PMID- 12793109
TI  - [The formation of neurons in the bone marrow, the dream of alchemy in the new
      millenium].
AB  - In rodents, bone marrow contains stem cells that have the potentiality to
      differentiate into mesodermal and non-mesodermal cells, both in vitro and in
      vivo. These cells can populate a wide panel of organs such as the liver, the
      brain, the lungs, the heart.... They appropriately differentiate according to the
      environment in which they migrate and are known to assume specific functions.
      Even in adult animals, these cells can migrate and differentiate. Such a
      potentiality suggests exciting therapeutic outcomes. Brain lesions could benefit
      of such techniques. These experimental protocols should be precisely controlled
      before their use in medicine in order to solve problems that still remain such as
      the permeability of the hemato-encephalic barrier, the integration of
      differentiated grafted cells into local functional neural networks.

PMID- 12793110
TI  - [The maxillary sinus: evolution and function in aging].
AB  - The maxillary sinus, or Highmore's antrum, is located in the maxillary bone. The
      maxillary, above the buccal cavity, below the orbital cavity and outside the
      nasal fossa, is going to take a part in the formation of the three cavities which
      surround it. Although voluminous, it is consists of a light bone. This
      distinctive feature is essentially due to the fact that the maxillary has a
      cavity. The maxillary sinus occupies the upper 2/3s of this maxillary bone. It is
      the largest of the facial structure's cavities. Its volume is very variable,
      depending on the individual, the condition of their edentulousness and their age.
      We find small, average or large sinuses. This sinus communicates with the
      corresponding nasal fossa by a canal. It opens at the level of the nasofrontalis
      duct by a meatic ostium, an ostium located at the top of the meatus nasi medius,
      i.e. under the floor of the sinus. This highly positioned drainage location
      easily explains the problems that sinus pathologies can come up against. The
      sinus is lined with a mucous membrane and we can point out that in the normal
      condition this mucous membrane adheres weakly to the bone. It is more or less
      thick as a function of the pathologies to which the sinus has been subjected, or
      even as a function of the geographical location where the individual lives. The
      imaging of this sinus as a function of age is not obvious due to the fact that it
      is invisible throughout embryonic and foetal development, and that it only
      becomes visible to X-rays relatively late, at about 6 years old. Its role is
      important at the level of the growth of the facial structure because it is always
      easier to have growth around cavities. It also has a mechanical role concerning
      the transmission of shockwaves during traumas. In old individuals, due to the
      condition of the edentulousness, the volume of the sinus is larger; in fact one
      can note the resorption of the alveolar bone. The maxillary sinus is a cavity
      which plays a very important role throughout an individual's existence because of
      the previously mentioned reasons, and which could be used during surgical
      reconstructions, by the partial filling of this space, to increase the quantity
      of usable bone (grafts...).

PMID- 12793111
TI  - [Vasculogenesis and angiogenesis: molecular and cellular controls. part I: growth
      factors].
AB  - Angiogenesis characterizes embryonic development, but occurs also in adulthood,
      under physiological circumstances like adaptation to muscular exercise or in
      pathology like cancers. Knowledge of these mechanisms has step forward partly due
      to knock-out mice that have allowed to devoid an exact role to the different
      growth factors that are involved. Interestingly, the same growth factors and
      their receptors are equally involved during development and adulthood. We have
      detailed here their respective role and how interactions between them leads to a
      newly formed vessel.

PMID- 12793112
TI  - [Vasculogenesis and angiogenesis: molecular and cellular controls. II. The
      interactions between the cell and its environment].
AB  - Angiogenesis defined as a new blood vessel formation from a preexisting vessel is
      initiated by angiogenic growth factors and their receptors, that induce
      endothelial cells migration and proliferation. Extracellular proteolysis is
      essential for deassembly et reassembly of endothelial cells to their
      environmental matrix. The aim of this review is to update data upon the role of
      the coagulation and fibrinolysis system, metalloproteinases and adhesion
      molecules during this step of angiogenesis.

PMID- 12793113
TI  - Laboratory tests for diagnosis of food allergy: advantages, disadvantages and
      future perspectives.
AB  - Numerous biological tests point to the diagnosis of food sensitization: detection
      of specific IgEs by Rast techniques, multi-detection assays, immunoblotting,
      screening of basophil activation (BAT or FAST), assays for leukotriene LTC4
      release (CAST), measurement of plasma histamine, serum tryptase, serum ECP,
      urinary EDN, completed by mannitol-lactulose test evaluating intestinal
      permeability, assay of fecal IgEs, Rast for specific IgG4. Primary screening for
      anti-food IgEs by multi-detection assays seeks justification from insufficient
      clinical data and false positive tests are common in patients sensitized to
      pollens or latex, on account of in vitro cross reactivities (CR). Multiple CR
      explain positive Rast to vegetal food allergens in such patients. Biological
      tests should not be performed as the first line of diagnosis. In vivo
      sensitisation is assessed by positive prick-tests, demonstrating the bivalence of
      allergens, as well as the affinity of specific IgEs, two conditions necessary to
      bridge membrane bound specific IgEs, leading to the release of mediators. Prick
      tests are closer to clinical symptoms than biological tests. However, the
      diagnosis of food allergy is based on standardised oral challenges. Exceptions
      are high levels of specific IgEs to egg (> 6 kUl/l), peanut (> 15 kUl/l), fish (>
      20 kUl/l) and milk (> 32 kUl/l), reaching a 95% predictive positive value. Rast
      inhibition tests are useful to identify masked allergens in foods. Research
      developments will have impact on the development of new diagnostic tools:
      allergen mixes reinforcing a food extract by associated recombinant major
      allergens, multiple combination of recombinant allergens (chips) or tests with
      synthetic epitopes aimed a the prediction of recovery. Laboratory tests take
      place in the decision free for the diagnosis for the food allergy and the follow
      up of the levels specific IgEs is a tool to assess outcome and contributes to
      predict recovery or persistent allergy. Up to now the significance of positive
      laboratory tests showing the implication of IgEs is at the crossroads of the
      allergist's and biologist's expertise.

PMID- 12793114
TI  - Food safety of allergic patients in hospitals: implementation of a quality
      strategy to ensure correct management.
AB  - Food allergy could affect up to 8% of children. Four cases of food anaphylaxis in
      hospitalized children are reported, pointing to the need of food allergenic
      safety procedures in hospital settings. The implementation of the operating
      procedure in hospital food production units (HFPU) of Nancy University Hospital
      is described. The dietetics Department developed on hypoallergenic diet and
      specific avoidance diets. Dieticians within HFPU managed the choice of starting
      materials, the circuit organization in order to avoid any risk of contamination
      during preparation and cooking of food, product traceability, and trained the
      staff of HFPU. Within the care units physicians, dieticians, nurses, hospital
      workers are involved in meal management. A diet monitoring sheet is integrated
      into the patient's nursing file and enables the dietician to validate the diet in
      the computer, the nurses to display the patient's diet on the schedule on the
      wall in their office. The hospital workers finally use a tray form indicating the
      patient's identity, his/her diet and the menu of the day. Such a procedure
      absolutely secures the whole circuit and specifies the responsibilities of each
      person, whilst ensuring effective cooperation between all partners. Since 1999,
      the implementation of this multi-step strategy has prevented from any further
      reaction in a department specialized for food allergies in children and in
      adults. As setting up food allergenic safety in hospitals in not addressed
      adequately in the European directives, it's judicious to draw attention of
      hospital catering managers and hospital canteen staff to this necessity.

PMID- 12793115
TI  - Asthma in Italian conscripts: a four year study.
AB  - BACKGROUND: Italian conscripts showed underdiagnosis and undertreatment of asthma
      in a previous 9-year study (1990-1998). METHODS: We extended those findings in a
      new 4-year study (1999-2002) by screening 28,327 18-year old males referred to La
      Spezia Military Navy Hospital for call-up visit. RESULTS: Asthma was diagnosed in
      1,847 conscripts (6.52%). Along the observational period there was a significant
      decrease of mild persistent asthmatic subjects (from 39.6 to 30.1%, p < 0.01).
      The use of inhaled corticosteroids and antileukotrienes significantly increased.
      However, about one third of the asthmatic subjects did not receive any treatment
      at all and about 40% of asthmatic subjects showed impaired spirometry.
      CONCLUSIONS: In this age, data show a partial success of educational efforts,
      since underdiagnosis and undertreatment are still present.

PMID- 12793116
TI  - Correlation between clinical classification, PEF and FEV1: guidelines and
      reality.
AB  - The currently proposed guidelines and consensus for asthma include Peak
      expiratory flow (PEF) and forced expiratory volume in the first second (FEV1) as
      two criteria to classify asthma severity. The report between these functional
      data and clinical classification degrees has been evaluated in 153 asthmatic
      patients. Concordance between functional evaluation and clinical degree has been
      found only for moderate persistent asthma but not for intermittent or mild
      persistent asthma. These results suggest that the correlation between clinical
      evaluation and lung function proposed in the guidelines must be reevaluated.

PMID- 12793117
TI  - Sublingual immunotherapy in the context of a clinical practice improvement
      program in the allergological setting: results of a long-term observational
      study.
AB  - The aim of this study was to assess the efficacy and safety of sublingual
      immunotherapy (SLIT) in a Clinical Practice Improvement (CPI) program carried out
      in allergology. The study was conducted between 1992 and 2001 using an
      observational type methodology in line with standard clinical practice. The
      program consisted of 4 basic steps: setting up of a decision-making tree;
      standardization of main diagnostic and therapeutic aspects; data collection;
      definition and evaluation of main clinical endpoints. Study patients were
      screened among 1508 patients with pollen and/or dust mite respiratory allergy,
      350 of which, one year after having experienced a pharmacological treatment
      failure, were administered immunotherapy by injection (n = 111) or alternative
      route (n = 239). For each one of the three immunotherapy treatment groups (nasal,
      SLIT or injective) there was a control group of patients who, despite their poor
      response to pharmacological treatment, continued with pharmacological therapy
      alone (n = 314 in total; 68, 192 and 54 respectively). The observation of 130
      SLIT patients, 106 of which were treated for at least 36 months, towards the
      control group evidenced that such therapy, apart from resulting efficient and
      particularly safe, has an unfailing protective effect against the development of
      asthma and new allergic sensitizations.

PMID- 12793118
TI  - Canadian integrated surveillance report: Salmonella, Campylobacter, pathogenic E.
      coli and Shigella, from 1996 to 1999.

PMID- 12793119
TI  - [What is your diagnosis? Pruritic urticarial papules and plaques of pregnancy].

PMID- 12793120
TI  - [Criteria for evaluating hip joint arthroplasty].
AB  - Development and state of the art of the Total Hip Replacement (THR) are reviewed.
      Progress since the introduction of the "low friction arthroplasty" by John
      Charnley/UK over 40 years ago consists first of all in an impressive reduction of
      the number and severity of complications: infection, failures of materials,
      thromboembolism and aseptic loosening. Current 10 year survival rates should not
      be lower than 97%. This high standard of THR performance has become the greatest
      obstacle to further progress. The most important factors for the assessment and
      the outcome of a THR are the operative (cementing) technique, the mechanical
      design of the prosthesis, the characteristics of the surfaces (implant, bone
      cement, bone) and the materials used. A prognosis of the survival of a THR can be
      made based on negative subjective clinical and negative objective criteria. On X
      ray films these criteria are shown first of all as changes (radiolucency,
      osteolysis, progressive migration) at the implant-bone interface and within the
      periprosthetic bone itself.

PMID- 12793121
TI  - [Erectile dysfunction in cardiovascular diseases].
AB  - After the acute phase, a patient who is diagnosed with cardiac or vascular
      disease becomes "chronically ill". This patient will then still spend many years
      without symptoms or impairments. One day, a percentage of such patients will be
      confronted with the problem of erectile dysfunction. Various studies have
      demonstrated that this problem occurs with a higher frequency in patients with
      cardiovascular diseases, in particular when they have to be treated for
      hypertension, diabetes mellitus or dyslipidemia. Very rarely are stenoses or
      occlusions found in the arteries responsible for penile circulation. More recent
      data indicates that a diffuse anomaly of the vascular endothelium is present, for
      which erectile dysfunction is a marker. Nowadays, medical care has achieved a
      better degree of standardization, not only thanks to knowledge about the effects
      of cardiovascular medication, but also because the physician can now prescribe
      drugs that treat erectile dysfunction.

PMID- 12793122
TI  - [Acute epigastric pain].
AB  - Epigastric pain is a frequent complaint in emergency patients and shows a wide
      spectrum of differential diagnostic possibilities. Dangerous causes with life
      threatening consequences have to be ruled out as soon as possible, including
      causes of extra abdominal organs (heart, great vesels). After checking for and
      adequate treatment of vital parameters an efficient management strategy should
      consider the acuteness of symptoms, as velocity of pain onset is often related to
      its seriousness (aneurysmatic rupture of great vessels, parenchymal damage or
      infarction). A rare cause of acute epigastric pain is bleeding or rupture of
      renal or hepatic cysts. Imaging techniques, such as ultrasound and computed
      tomography, are helpful in finding the correct diagnosis without loosing to much
      time. Therapy depends on aetiology and dignity of the lesion, often an invasive
      surgical intervention is the only possibility to confirm the correct diagnosis.

PMID- 12793123
TI  - [Generalized muscle pain in a 67-year-old patient. Myalgia/myositis in therapy
      with Zocor].

PMID- 12793124
TI  - The detection of morphine and codeine in human teeth: an aid in the
      identification and study of human skeletal remains.
AB  - When studying unidentified putrefied or skeletonised human remains it may be
      difficult to obtain information on drug habits which may prove important for the
      construction of a biological profile or lead to hypotheses on the manner of
      death. The detection of morphine and codeine in teeth from human remains may
      prove crucial in obtaining such information and thus give forensic odontology and
      anthropology a further tool for identification. Because teeth can be an important
      deposit of exogenous substances accumulated both in the pulp and in the calcified
      tissues, they are an invaluable source of data from a toxicological point of
      view. The authors therefore tested 3 groups of teeth for morphine and codeine:
      the first group consisted of artificially aged teeth from individuals known to
      have died of heroin overdose; the second, of teeth from individuals with no
      history of drug abuse; the third, of teeth from cases of burnt, putrefied and
      skeletonised remains found in conditions strongly suggestive of a drug-related
      death. Results showed that in groups 1 and 3 morphine and codeine could still be
      identified in the teeth, proving that these tissues may be a reliable source for
      toxicological information concerning the history of the individual. Further
      studies are needed to verify whether the substances detected reflect drugs in
      circulation in an acute phase (and therefore present in blood vessels in the
      pulp) or whether they represent drugs which have percolated and been stored in
      dentine and enamel and thus denote a history of drug abuse. Nonetheless this
      study shows that teeth may be an important source of toxicological information in
      the forensic scenario.

PMID- 12793125
TI  - Are a minimum number of concordant matches needed to establish identity in
      forensic odontology?
AB  - Forensic odontology plays an important role in the identification of human
      remains. While numerous studies have proven conclusively the uniqueness of the
      human dentition, forensic odontologists worldwide remain divided about the need
      for a minimum number of concordant points to confirm dental identification. This
      study reviewed 690 cases from the archives of the Forensic Odontology Unit, The
      University of Adelaide, to determine the validity of using a minimum number of
      concordant points to positively identify human remains. It was found that
      positive identification had been established using a varying number of concordant
      points. Although the incidence of positive identification was more frequent with
      a minimum of 12 concordant points, there were numerous cases where 12 or more
      concordant points failed to achieve a positive identification. Identities were
      also confirmed in some cases using less than 12 points of correspondence. There
      appears to be no basis for defining a minimum number of concordant points
      necessary before a positive identification can be made on dental evidence.
      Rather, the findings of this study reinforce the view that each case has its own
      individuality and should be treated as such.

PMID- 12793126
TI  - Forensic aspects of guidelines.
AB  - In lawsuits concerning medical or dental litigation a question regularly arising
      is whether the treatment was in accordance with best practice. In recent times
      doctors and dentists have increasingly been confronted with so called
      recommendations, guidelines, directives etc., which should help them to reach the
      required standard. They are theoretically legally binding in different degrees,
      for example, guidelines are not binding where directives are. Such differences
      however can hardly be expected to be reflected in everyday legal routine and no
      matter whether the doctor has deviated from a recommendation, a guideline or a
      directive, it will complicate the chances of success in a lawsuit. It is
      therefore important to be aware of these potential judicial implications when
      formulating guidelines and other instructions or recommendations in order to
      avoid paving the way for legal pitfalls, which at the very least would lead to
      over-defensive medical/dental practice. Nevertheless, guidelines can be of value
      as long as they are not rigid regulations but rather readily usable,
      comprehensible information on the current state of practice. They could then also
      have a positive influence on judicially commissioned expert evidence.

PMID- 12793127
TI  - Copper vapour laser ID labelling on metal dentures and restorations.
AB  - Denture marking is accepted as a means of identifying dentures and persons in
      geriatric institutions, or post-mortem during war, crimes, civil unrest, natural
      and mass disasters. Labelling on the acrylic resin component of the denture can
      easily be damaged or destroyed by fire but on cobalt-chromium components it would
      be more resistant. A copper vapour laser (CVL) can be used to label the cobalt
      chromium components of dentures and metal restorations easily, and legibly, and
      miniaturised for the incorporation of more personal particulars necessary for the
      identification of the deceased person. The CVL beam is focussed by its optics and
      delivered to the material surface by the two-axis scanner mounted with mirrors. A
      personal computer controls the movement of the scanner and the firing of the CVL.
      The high peak power of the pulsed CVL is focussed to very high energy density
      producing plasma ablation of the alloy surface. Very fine markings of a few
      microns width can be produced enabling the storage of detailed information of the
      deceased person on a metal surface for the purpose of rapid identification.

PMID- 12793128
TI  - [Basic tendencies in improving diagnostics and growing significance of invasive
      methods of study].

PMID- 12793130
TI  - [Role of electron-beam tomography in diagnosing patency of aortocoronary and
      mammary-coronary shunts (from data from a 3-year study)].
AB  - AIM: To assess informative value of electron-beam tomography (EBT) and to compare
      dynamics of occlusive defects of autovenous and autoarterial shunts. MATERIAL AND
      METHODS: 36 patients with coronary heart disease entered the study. All the
      patients have undergone coronary artery bypass operation and/or mammarocoronary
      bypass operation (CABO and MCBO, respectively). For three years after the surgery
      the patients were annually examined with EBT-shuntography. The contrast agent was
      injected intravenously in a dose 135-140 ml with the injection rate 3.5-4.0 ml/s.
      In addition to EBT-shuntography, selective x-ray contrast shuntography was
      conducted one year after CABO. RESULTS: By a comparative analysis, EBT
      sensitivity and specificity in examination of autovenous shunts patency is 100%,
      in assessment of patency of mammary shunts is 93 and 100%, respectively. The 3
      year retrospective analysis has revealed occlusions in 17.1% venous shunts and
      2.7% arterial ones in the first year after CABO and MCBO, 5.2 and 2.8% in the
      second year, respectively, and in 1.8% venous shunts in the third year.
      CONCLUSION: EBT-shuntography is a highly informative non-invasive method of
      diagnosis of aortocoronary shunts patency.

PMID- 12793129
TI  - [Current aspects of diagnosis and treatment of symptomatic arterial hypertension
      of adrenal genesis].
AB  - AIM: To analyse the experience in diagnosis and treatment of arterial
      hypertension (AH) of adrenal genesis. MATERIAL AND METHODS: A total of 243
      patients with adrenal AH (mean age 46.3 +/- 3.2 years) were examined. 134 of them
      had endogenic adrenohypercorticism (EAH), 62--primary hyperaldosteronism (PHA),
      47--chromaffin tissue tumors (CTT). Diurnal urinary excretion of adrenal hormones
      (epinephrine, norepinephrine, aldosteron, hydrocortisone) and peripheral blood
      hormones (aldosteron, renin, hydrocortisone, ACTH) were measured. Topic diagnosis
      was made with ultrasound, computed tomography, MR-imaging, angiography, adrenal
      venous sampling and 123I-MIBG scintigraphy. RESULTS: Adrenalectomy was made in
      224 patients (predominantly with tumor lesions). 19 patients (idiopathic
      hyperaldosteronism, advanced adrenocortical carcinoma) were treated
      conservatively (calcium antagonists, ACE inhibitors, AT1-receptor blockers,
      spironolacton). Good results of the surgical treatment were achieved in 60%
      patients with aldosterone-producing adenoma and adrenal Cushing's syndrome as
      well as in 80.5% patients with pheochromocytoma. Long-term outcomes depend on
      hypertension duration, histologic type of the tumor, age and family hypertension
      history (risk of essential hypertension). CONCLUSION: Hypertension of adrenal
      origin occurs more frequently than it was supposed previously. Its late diagnosis
      may be due to lack of typical signs and symptoms, insufficient application of
      novel diagnostic techniques and poor alertness of physicians. It is recommended
      to include tests for adrenal hormones in urine and blood and ultrasound
      investigation of the adrenals in a complex of primary examination of patients
      with severe refractory hypertension.

PMID- 12793131
TI  - [Evaluation of myocardial perfusion in patients with hypertrophic cardiomyopathy
      in comparison with clinical and echocardiographic data].
AB  - AIM: To study peculiarities of myocardial perfusion in patients with hypertrophic
      cardiomyopathy (HCMP) in correlation with clinical and echocardiographic data.
      MATERIAL AND METHODS: 62 patients with HCMP (23 females and 39 males, mean age
      44.4 +/- 11.2 years, the disease duration 13.0 +/- 10.4 years) have undergone
      ECG, 24-h ECG monitoring, echocardiography, perfusion scintigraphy of the
      myocardium with 99m-TcMIBI at rest and in combination with bicycle ergometry. The
      patients were divided into two groups: 35 patients of group 1 had moderate left
      ventricular hypertrophy (the septal thickness in diastole under 20 mm; 27
      patients of group 2 had severe hypertrophy (the thickness was over 20 mm).
      RESULTS: Dyspnea and syncopal states occurred more frequently in patients from
      group 2. They also had a higher functional class of heart failure (2.0 +/- 0.8
      and 1.2 +/- 0.7 for group 1 and 2, respectively, p < 0.05). Cardiac performance
      was significantly higher in patients of group 1. The size of the left atrium,
      left ventricular myocardium mass, the septal thickness and thickness of posterior
      wall of the left ventricle, gradient of pressure in the outflow tract of the left
      ventricle proved higher in patients of group 2. Deep stable defects of myocardial
      perfusion were detected in 5 (15%) patients of group 1 and 10 (37%) patients of
      group 2. Transient defects of myocardial perfusion were found in 9 (26%) patients
      of group 1 and 12 (44%) patients of group 2. The index of myocardial ischemia in
      group 1 patients was significantly lower than in patients of group 2 (3.5 +/- 2.2
      and 8.3 +/- 2.5, respectively, p < 0.05). CONCLUSION: Patients with severe
      hypertrophy of the left ventricle had severe clinical picture, low exercise
      tolerance, marked hemodynamic changes, more frequent defects of left ventricular
      perfusion defects compared to patients with moderate hypertrophy of the left
      ventricular myocardium.

PMID- 12793132
TI  - [Role of computed angiopulmonography in current diagnosis of pulmonary artery
      thromboembolism].
AB  - AIM: To study potentialities of tomographic methods in diagnosis of pulmonary
      artery thromboembolism (PATE). MATERIAL AND METHODS: Electron-beam tomography
      (EBT) was used for diagnosis in 34 patients (mean age 41.3 +/- 16.5 years)
      suspected of PATE (Imatron C-150 unit, USA). The procedure included standard
      examination of the lungs and EBT angiopulmonography in intravenous introduction
      of the contrast agent (80-100 ml, the rate 3-3.5 ml/s). RESULTS: The pulmonary
      artery was found to contain thrombi in 56% patients. 18% of PATE patients had
      pulmonary infarction. A complete coincidence of EBT and scintigraphy was
      registered in 31% cases, no PATE by both methods was in 19% cases.
      Angiopulmonography and EBT findings were the same. In 1 case the result of
      pulmonary scintigraphy was false negative. 24% patients showed symptoms of
      thrombophlebitis or varicosity of the lower limbs. EBT has detected signs of PATE
      in 83% of them. CONCLUSION: EBT-angiopulmonography is a precise, highly
      informative non-invasive method in diagnosis of PATE.

PMID- 12793133
TI  - [Preliminary data on combined assessment of tolerance to exercise, left
      ventricular contractile function in ischemic heart disease patients taking
      bradycardic agents].
AB  - AIM: To study effects of bradicardia induced by atenolol, diltiazem and ivabradin
      on exercise tolerance, myocardial perfusion and left ventricular contractile
      function in patients with stable angina pectoris. MATERIAL AND METHODS: The trial
      included 7 male patients aged 57 +/- 2.6 years with coronary heart disease,
      stable angina of functional class II free of cardiac failure and severe arterial
      hypertension, with a positive and reproducible VEM test after therapy
      discontinuation. For 10 consecutive days with 5-day intervals, all the patients
      received atenolol, diltiazem, ivabradin in doses lowering heart rate at rest by
      20% from the initial level. Before the treatment all the patients were studied
      with VEM test, perfusion synchronized single-photon emission computerized
      tomoscintigraphy of the myocardium (PSSPECT) at rest and exercise. On day 10 of
      each drug intake PSSPECT and VEM test were performed if the expected heart rate
      was achieved. RESULTS: Each of the studied drugs resulted in a 22-24% reduction
      in the heart rate at rest accompanied by a significant rise in exercise
      tolerance, improvement of performance and myocardial perfusion. There were no
      significant changes in left ventricular contractility. CONCLUSION: A 20%
      reduction in resting heart rate due to monotherapy with drugs having a
      bradicardic effect leads to positive changes in exercise tolerance and myocardial
      perfusion.

PMID- 12793134
TI  - [Sjogren's syndrome in chronic hepatitis C: clinical features and diagnosis].
AB  - AIM: To examine clinical features of Sjogren's syndrome (SS) and morphological
      picture of the lesser salivary glands (LSG) in chronic hepatitis C (CHC).
      MATERIAL AND METHODS: The examination of 42 patients with SS and chronic HCV
      infection (mean age 44.3 +/- 13.7 years) has detected signs of chronic hepatitis
      and hepatic cirrhosis, respectively, in 31 (71.4%) and 11 (26.2%) patients. "Dry
      syndrome" was diagnosed by criteria of European SS Study Group. LSG biopsy of the
      lower lip was conducted in 23 (54.7%) of 42 patients. RESULTS: The "dry" syndrome
      in CHC ran subclinically in 73.8% patients. Apparent symptoms of SS were seen
      primarily in middle-aged and aged women with CHC history over 10 years. The first
      signs of SS occurred in 25 (59.5%) patients 2.9 +/- 3.1 years prior to diagnosis
      of hepatic disease. All the patients had xerostomy. Xerophthalmia was recorded
      1.5 times less frequently. In 16 (47.1%) patients with CHC "dry eye" and in 6
      (17.6%) patients dry keratoconjunctivitis were detected. Pathohistological
      changes of LSG were diagnosed in 21 (91.3%) of 23 patients with CHC. In the
      majority of cases (86.9%) the glands exhibited insignificant inflammatory
      infiltration and advanced fibrosis. LSG in CHC is characterized by fibrosis
      prevalence over cell infiltration. 83.3% CHC patients had SS and other
      extrahepatic lesions. SS was most evident in 28.6% CHC patients with
      cryoglobulinemia. CONCLUSION: Registration of SS symptoms in CHC patients depends
      on targeted examination of patients with chronic HCV infection. The severity of
      the symptoms correlates directly with the infection duration and age of the
      patient. LSG lesions in CHC patients with SS are characterized by fibrosis pre
      domination over cell infiltration.

PMID- 12793135
TI  - [Needle biopsy in diagnosing primary mediastinal tumors].
AB  - AIM: To assess the potential of biopsies with the thick cutting needle of
      anterior mediastinum tumor. MATERIAL AND METHODS: Biopsy with the use of the
      thick cutting needle (Baxter Healthcare Corporation, length 150 mm, thickness 2.5
      mm, length of the cutting channel 20 mm) of a primary mediastinal tumor was made
      in 12 patients. RESULTS: The findings were the following: 8 cases of primary
      mediastinal B-cell lymphosarcoma, 1 case of T-cell lymphosarcoma with involvement
      of the mediastinum, 2 cases of thymic carcinoma, 1 case of pituitary tumor.
      Mediastinal puncture was controlled by ultrasound which secured accurate position
      of the needle and safe conduction of the puncture. CONCLUSION: Puncture biopsy
      with the thick cutting needle of anterior mediastinum tumor provides short
      duration of the diagnostic process and correction of the treatment policy.

PMID- 12793136
TI  - [Plasmic activity of phospholipid membranes in nephritis].
AB  - AIM: To study activity of plasmic phospholipid membranes (PPM) in patients with
      chronic nephritis (CN) as regards clinical-laboratory and morphological
      characteristics of the disease. MATERIAL AND METHODS: 10 patients with chronic
      mesangial glomerulonephritis (CMG) and 4 patients with chronic drug-induced
      tubulointerstitial nephritis were examined. All the patients had moderate
      arterial hypertension including 5 patients with CMG combined with nephrotic
      syndrome. 9 patients had elevated blood creatinine (up to 500 mcmol/l).
      Measurements were made of routine laboratory indices, blood coagulation and
      paracoagulation, Willebrand's factor (WF), aggregation time (AT), phospholipid
      activation of blood coagulation (FABC), morphological indices of activity and
      sclerosis. RESULTS: In spite of chronic latent intravascular blood coagulation,
      CN was characterized by apparent lowering of FABC which was more evident in CMG.
      There was a weak correlation between a FABC fall and the level of proteinuria,
      lipidemia, AT of platelets, indices of activity. Some parallels exist between
      creatininemia and activity of PPM. A close reverse relationship was found between
      FABC and WF, and a direct one between FABC and sclerosis index. CONCLUSION:
      Subnormal PPM activity in CN correlates with organic microthrombi formation and
      promotes the discussion of both mechanisms of FABC formation disturbances and
      possible ways of PPM consumption including enhanced diffusion into the mesangium
      in progressing nephrosclerosis.

PMID- 12793137
TI  - [Ileocecal valve insufficiency as visceral sign of undifferentiated connective
      tissue dysplasia].
AB  - AIM: To study prevalence of markers of connective tissue dysplasia (CTD) in
      patients with primary insufficiency of ileocecal valve (PIIV). MATERIAL AND
      METHODS: The trial included 87 patients (21 men and 66 women aged 13 to 64 years)
      with irrigoscopy-documented barium reflux into the small intestine. The
      occurrence of external phenotypical markers of CTD was studied at general
      examination and antropometry, of visceral ones--at ultrasound investigation of
      the heart, abdominal organs and the kidneys. The state of the connective tissue
      was assessed by skin biopsy histology. RESULTS: PIIV patients demonstrated a
      great number of dysembryogenic stigma typical for CTD: asthenic constitution,
      hypotrophy, chest deformation, foot and spine ligaments weakness, etc. A radial
      lacunar type of the iris of the eye was described for the first times among
      external CTD phenotypical markers. Such visceral CTD markers as mitral prolapse,
      left ventricular false chorda, gallbladder deformity, nephroptosis occurred in
      the PIIV patients significantly more frequently. Morphological characteristics of
      the skin in PIIV patients were similar to those registered in patients with
      cardial manifestations of CTD. CONCLUSION: The above external and visceral
      phenotypical markers and skin morphology give arguments for referring PIIV to
      signs of CTD. Such position can open new prospects for pathogenetic treatment of
      PIIV.

PMID- 12793139
TI  - [Study based on the WHO Monika program on the connection between psychosocial
      risk factors and ischemic heart disease in men aged 25-64 in Novosibirsk].
AB  - AIM: To study correlations between coronary heart disease (CHD) and psychosocial
      risk factors. MATERIAL AND METHODS: CHD affected more frequently workers engaged
      in hard physical labour, in poorly educated persons; the least CHD morbidity was
      recorded in managers and highly educated persons. CHD males think of their health
      much worse than males free of CHD. The former smoked much more before CHD
      diagnosis, but when CHD comes they quit and reduce smoking much more frequently.
      This fact explains why smokers are encountered among CHD patients two times less
      frequently than in CHD-free males. In spite of stronger motivation for adequate
      diet, CHD males changed their nutrition pattern only in 3.7%. CHD males sleep
      worse: good sleep was registered in CHD-free males two times more frequently.
      Psychological risk factors such as personal anxiety, sleep disorders were
      reported much more frequently in CHD patients proving the fact of social stress
      involvement in development of CHD. So-called coronary behavior was observed in
      both groups of males with the same rate. Thus, the coronary behavior is not
      associated with CHD. CONCLUSION: Development of CHD is associated not with the
      behavior but its components (depression, anxiety, etc.).

PMID- 12793138
TI  - [Immediate and long-term outcomes after "Ephesos" coronary stent implantation in
      patients with stable or unstable angina].
AB  - AIM: An open non-randomized trial was initiated to assess clinical and
      angiographic results of using the coronary stent "Ephesos" in 457 patients with
      stable or unstable angina pectoris and native coronary affections. MATERIAL AND
      METHODS: 268 stents have been implanted in 231 patients with stable angina (SA)
      and 271 stents--in 226 patients with unstable angina (UA). 46% lesions were
      complicated. The length of stenosis was 12.9 +/- 6.7 mm in the group SA and 14.1
      +/- 7.4 mm in the group UA, 30% stenoses were long. RESULTS: Successful stenting
      was stated in 99% without cases of acute thrombosis. Non-fatal myocardial
      infarction took place in hospital in 1.3% of SA patients and in 2.6% of UA
      patients. Incidence of cardiac complications (death, recurrent angina pectoris,
      myocardial infarction, restenosis, repeated revascularization) for 6-month follow
      up was 15.6% in SA group and 18.1% in UA group. At angiographic control, the
      index of vascular diameter loss made up 0.22 +/- 0.2 in SA group and 0.3 +/- 0.27
      in UA group. Incidence of restenosis was 12 and 14%, respectively. 18-month
      follow-up found no differences in frequency of complications: 21.6 and 22.6% in
      groups SA and UA, respectively. CONCLUSION: Implantation of the stent "Ephesos"
      is effective in prevention of thrombosis and restenosis in patients with stable
      or unstable angina pectoris at high risk of intervention.

PMID- 12793140
TI  - [Comparative effectiveness of lotensin and capoten in patients with chronic
      cardiac failure].
AB  - AIM: To compare clinical response to captopril (capoten) vs benazepril (lotensin)
      in patients with chronic cardiac failure (CCF) as well as their influence on
      central hemodynamics, some indices of platelet hemostasis, myocardial ischemia
      degree, exercise tolerance. MATERIAL AND METHODS: 54 patients with CCF (NYHA FC
      II and III) entered the trial. 26 patients received captopril (capoten) in a dose
      25-75 mg/day (group 1) while 28 patients were given benazepril (lotensin) in a
      dose 5-30 mg/day for 4 weeks (group 2). Group II was treated for the following 24
      weeks. The results were assessed with electro- and echocardiography, bicycle
      exercise test, platelet aggregation measurement and by clinical symptoms.
      RESULTS: A positive clinical response was registered to both the drugs which
      improved the functional class, exercise tolerance, platelet aggregation, reduced
      the number of arrhythmia and myocardial ischemia episodes. Long-term treatment
      with lotensin resulted in further improvement of clinical and laboratory indices.
      Side effects, in which lotensin discontinuation is needed, were absent. Lotensin
      was more potent than capoten in reducing episodes of ST expression on ECG and
      episodes of painless myocardial ischemia.

PMID- 12793142
TI  - [A case of Ehlers-Danlos syndrome with subsequent formation of aneurysms of
      femoral, carotid ].

PMID- 12793141
TI  - [Experience in clinical use of primalan (mequitazine) in allergology].
AB  - AIM: To study efficacy of primalan (mequitasine) in the treatment of allergic
      rhinoconjunctivitis and chronic recurrent urticaria. MATERIAL AND METHODS: The
      study included 140 patients. Of them, 60 patients had allergic rhinitis, 80
      patients had chronic recurrent urticaria. All the patients received primalan
      (mequitasin) in a dose 10 mg/day (5 mg twice daily or a single dose 10 mg). The
      disease symptoms and side effects of primalan were assessed for 28 days of the
      treatment. RESULTS: Primalan (mequitasin) proved to be highly effective against
      allergic rhinitis (good and very good response--76%, satisfactory--20%) and
      chronic recurrent urticaria (the response in 90% patients). Good primalan
      tolerance was reported. Side effects were moderate and did not require the drug
      withdrawal (sleepiness in 6.6%, dryness of the mucosa in 5%). CONCLUSION:
      Primalan (mequitasin) can be recommended for wide application in therapy of
      allergic rhinitis and chronic recurrent urticaria.

PMID- 12793143
TI  - [Case of diagnosing transient myocardial ischemia in complete block of the His
      bundle].

PMID- 12793144
TI  - [Case of diagnosing acute dissecting aneurysm of the thoracic aorta, complicated
      by pericarditis].

PMID- 12793145
TI  - [Difficulties in diagnosing nodular polyarteritis].

PMID- 12793146
TI  - [Long term course of multifocal fibrosis].

PMID- 12793147
TI  - [Endophytic cancer of the esophagus with isolated metastasis to the right section
      of the myocardium and massive thrombus formation in its cavity].

PMID- 12793148
TI  - [Erosive duodenitis and enterogenic sepsis as a complication of celiac disease].

PMID- 12793149
TI  - [Casuistic cases in differential diagnosis of stomach cancer].

PMID- 12793150
TI  - [Prenatal diagnosis of congenital and hereditary diseases].

PMID- 12793151
TI  - [Some aspects of laboratory diagnosis of viral hepatitis B and C].

PMID- 12793152
TI  - [Principles of medicine, based on evidence in pharmacotherapy for circulatory
      diseases].

PMID- 12793153
TI  - [Clinical perspectives for using scintigraphy with 123I-metaiodobenzylguanidine
      for assessing the status of myocardial sympathetic nervous system status].

PMID- 12793154
TI  - Evidence-based clinical practice: a philosophy, process, and product.

PMID- 12793155
TI  - The spirit of oncology nursing care.
AB  - Cancer awakens the need to honour our spirit. The resiliency of the human spirit
      helps patients and families find strength and hope and move forward on their
      journey. As oncology nurses, we empower families by connecting with and sharing
      our own spirit, honouring and being present to their journey, and guiding them
      forward as they anticipate challenges ahead. Caring isn't about doing for, but
      being there and being the wind behind the sails. When we connect with our spirit,
      we stay open to the unfolding mystery of life. Allow mystery and discovery in
      your life to drive your spirit of caring and to remind you to look for the
      rainbows.

PMID- 12793156
TI  - The 2002 Helene Hudson Memorial Lecture. Healing conversations in the face of
      persistent or recurring cancer.

PMID- 12793157
TI  - Patient and family satisfaction with cancer-related information: a review of the
      literature.
AB  - Individuals and families confronted with cancer experience many and varied
      educational needs. Cancer education is an important aspect of their care. Yet,
      over the past three decades, the literature has consistently identified that many
      patients and family members are dissatisfied with cancer education. This paper
      examines the literature relevant to one aspect of satisfaction with cancer
      education, patient and family member satisfaction with cancer-related
      information, according to patient, provider, and information factors. Gaps in the
      research are identified and discussed in relation to future research
      recommendations. The paper concludes with applications to clinical practice.

PMID- 12793158
TI  - Perception of risk and surveillance practices for women with a family history of
      breast cancer.

PMID- 12793159
TI  - Determining the process of providing quality end-of-life care to hospitalized
      adult medical patients: the perspectives of nurses.

PMID- 12793160
TI  - Decision-making in adolescent oncology patients.

PMID- 12793161
TI  - [Statistical cause and association (I). Critique of the cause].

PMID- 12793162
TI  - [Familial Mediterranean fever].

PMID- 12793163
TI  - [News coverage of trauma].

PMID- 12793164
TI  - [Event, stress and psychological trauma].
AB  - The study on stress and trauma leads us to distinguish between two categories of
      events: those that involve constraint as opposed to those that involve intrusion.
      This distinction is more than just a philosophical speculation since it allows us
      to infer clinical manifestations of wide ranging acute disturbances while in the
      field, as well as the manifestations of highly characteristic delayed
      disturbances that can sometimes arise month after exposure to trauma. The
      epidemiology of delayed manifestations related to psychological trauma indicates
      that these are common disturbances marked by their persistence and chronicity.
      These manifestations present a variety of public health problem: the need to
      anticipate and prepare acute rescue efforts to be introduce in case of disasters,
      the need for specific and extended individual follow-up, and also, from a medico
      legal perspective, the question of compensation that may arise later on.

PMID- 12793165
TI  - [Individuality of psycho-traumatism and psycho-traumatized people].
AB  - Clinical aspects of post-traumatic psychiatric disorders are now well-known. But
      it might be advisable to not extend wrongly the field of these disorders. Authors
      emphasize differences between life event and traumatic event, and dwell on the
      singularity of trauma which gathers of subjectivity. By another way they describe
      specific characteristics of different traumatisms, at any age. At last, they
      recall the risks connected to some professions, especially firemen, policemen and
      all rescuers.

PMID- 12793166
TI  - [Psychological trauma: intrusion and unveiling].
AB  - Effects of psychical trauma are frequently described in our contemporary culture,
      in contexts as diverse as war, assault and disasters of many kinds. These various
      types of events themselves are not new, but what is more emphasised today is
      their impact on the overall group. Although traumatic events may affect sizeable
      populations or sub-populations, Psychical trauma involves a subjective
      specificity that cannot be reduced simply to a generalised disorder of the
      emotions and of stress. It relates back to the most profound aspects of being, of
      the subject in his relationship to language. Trauma produces the conditions of a
      veritable forcing of the psychical apparatus and an unveiling of a real of the
      subject which is subsequently expressed through symptoms of repetition, as seen
      in PTSD.

PMID- 12793167
TI  - [Traumatic repetition syndrome].
AB  - Central point of posttraumatic psychic troubles, the traumatic repetition
      syndrome is present either directly, or after a variable time. Clinic is based on
      nightmares and flash backs, but also contains lots of non-specific disorders,
      according to patient personality. One characteristic of this clinic is its
      eclipse evolution, with recurring symptoms which appear suddenly and sometimes
      vanish.

PMID- 12793168
TI  - [Group care of psychological trauma].
AB  - The teamnet care of patients suffering from a psychological traumatism is
      essential in overall process. Taking care of the patient takes place immediately
      after the event, but also in the few following days. This requires a codified
      organisational plan. Here, the creation and organisation of a psychological unit,
      the national teamnet care of patients, medical emergency and the specific cases
      of acute care wards are approached successively.

PMID- 12793169
TI  - [Individual treatment of psychological trauma].
AB  - Situations that confront the individual with the question of death, and create
      difficulties in his life, are numerous. The encounter can be traumatic and lead
      the subject to isolate himself from the world of speaking beings. It is important
      to be able to make an offer of treatment without delay. By encouraging the
      subject to resume a relationship of speech, one must progressively bring him out
      of the very private bond that ties him to the trauma.

PMID- 12793170
TI  - [The long-term course of psychological trauma: a multiplicity of outcomes].
AB  - The evolving severity of psychical trauma is measured on a scale of many years.
      It is assessed in relation to the upheaval that the traumatic event introduces in
      the life of a subject: in terms of the prior organization of his psychical life
      as in the relationships that he maintains with his social circle.

PMID- 12793171
TI  - [Medico-legal aspects of post traumatic disorders and their after-effects].
AB  - The psycho-traumatic situations are numerous with sometimes very invalidating
      consequences for the subjects which were exposed. The question arises then of a
      possible repair. The stacks are different for every wounded person. It could'nt
      be possible to envisage them only under the angle of a financial compensation.
      The medico-legal expertise is an essential phase in the progress towards a
      possible taken out of the influence of the trauma. The decree of January 10, 1992
      concerning the repair of the war psychological troubles opens a new area in the
      consideration of a very actual problem.

PMID- 12793172
TI  - [Primary care in Britain and North America].

PMID- 12793173
TI  - [Diagnosing disorders of hemostasis and coagulation].

PMID- 12793174
TI  - [Disorders of water, electrolytes and acid-base equilibrium].

PMID- 12793175
TI  - [Diagnosing palpitations].

PMID- 12793176
TI  - [Angiomas].

PMID- 12793177
TI  - [Antibiotic prescription monitoring].

PMID- 12793178
TI  - [Economics of health care consumption].

PMID- 12793179
TI  - [Biologic effects of microwave radiation].

PMID- 12793180
TI  - Serologic profile of Epstein-Barr virus infection in acute infectious
      mononucleosis.
AB  - The aim of our study was to determine classes of antibodies in different clinical
      forms of Epstein-Barr Virus (EBV) primary infections. The investigation included
      100 patients with acute mononucleosis who were hospitalized at the Clinic for
      Infectious Diseases in Novi Sad during 1995-1997. Apart from clinical and
      laboratory parameters, 5 different ELISA assays were performed: IgM EBVVCA, IgG
      EBVVCA, IgG EBNA, IgA EBVEA and IgG EBVEA. All patients were IgM EBVVCA positive,
      only 42% IgG EBVVCA positive and 6% IgG EBNA positive. Antibodies due to EBVEA
      IgA were established in 58% of patients and IgG class in 41%. Serologic profile
      of early EBV primary infection was established in 25%, acute EBV primary
      infection in 69% and late EBV primary infection in 6%. A statistically
      significant difference regarding absolute lymphocyte count and serologic response
      to early antigens of EBV infection was established in patients with positive
      findings. Clinical findings in the throat correlated with serologic response to
      early EBV proteins. We didn't find any correlation due to duration of illness,
      fever, clinical forms of EBV primary infection and liver damage. Paul Bunnell
      test was positive only in 42% of our patients, with significantly higher number
      of negative results in groups of early and late EBV primary infections.

PMID- 12793181
TI  - [Dialysis as a risk factor for development of atherosclerosis].
AB  - INTRODUCTION: Atherosclerosis is a major risk factor for increased cardiovascular
      morbidity and mortality in dialysis patients. First clinical symptoms are usually
      associated with initial atherosclerotic changes of blood vessels. The aim of this
      study was ultrasound evaluation of intima media thickness (IMT) of carotid
      arteries in dialysis patients and its correlation with certain risk factors.
      PATIENTS AND METHODS: IMT was measured in 45 dialysis patients with no signs of
      cardiovascular diseases: 15 continuous ambulatory peritoneal dialysis (CAPD)
      patients, 30 hemodialysis (HD) patients and in 20 healthy controls. IMT was
      correlated with certain risk factors for atherosclerosis (general parameters-
      age, gender, duration of dialysis, cause of renal diseases, parameters of
      nutrition, parameters of calcium and phosphorus metabolism, lipid parameters,
      blood pressure and smoking). RESULTS: The mean carotid artery IMT was
      significantly higher in dialysis patients than in the control group (p < 0.05).
      In addition, the mean IMT was statistically significantly higher in PD than in HD
      patients (p < 0.05). In CAPD patients there was a significant correlation between
      IMT and total and LDL cholesterol. In the second group (HD patients) IMT
      significantly correlated with diastolic blood pressure, BMI and smoking.
      CONCLUSION: Although atherosclerotic cardiovascular disease may not manifest in
      dialysis patients, IMT of carotid arteries significantly increases. Major risk
      factors affecting IMT are lipid disturbances in patients on peritoneal dialysis
      and hypertension, obesity and smoking in HD patients.

PMID- 12793182
TI  - [Epidemiology of mental disorders in the North Banat region].
AB  - INTRODUCTION: Mental disorders are recognized as a significant socio-medical
      problem within WHO European Region with prevalence of 5%. They constantly have an
      increasing rate and comprise series of pathologies including neuroses and
      psychosocial pathologies, organic psychoses and neural disorders. Over the past
      decade, as a result of crisis, enhancement of mental disorders has been
      established in our population. The objective of this paper was to analyze
      occurrence and epidemiology of mental disorders in adult population of the North
      Banat region in the period from 1997 to 2000. METHODOLOGY: We performed a
      comprehensive measurement and analysis of registered morbidity using official
      statistics issued by departments of general practitioners. RESULTS AND
      DISCUSSION: We analyzed registered morbidity in 6 health centers and established
      that neural-, stress- and somatotropic disorders make 3-7% of general morbidity
      in regard to 10 most frequent groups of illnesses. Prevalence of mental disorders
      differs in the examined region, but not significantly. We assume that this is the
      result of different approaches to this problem by physicians who establish the
      diagnosis. CONCLUSION: As our current research shows, mental disorders had a
      slight increasing rate during the last five years. Difference regarding health
      care approach is apparent, as well. We propose a health care program for mental
      health of the entire population as well as appropriate education of health
      professionals.

PMID- 12793183
TI  - [Association of class II HLA antigens and insulin-dependent diabetes mellitus in
      the population of Vojvodina].
AB  - INTRODUCTION: Class II HLA antigens were investigated in a group of 28 patients
      with insulin-dependent diabetes mellitus (IDDM) and 218 healthy unrelated persons
      (control group) from Vojvodina. MATERIAL AND METHODS: We used a modified two
      colour immunofluorescence method (serologic technique) to determine the phenotype
      of DR and DQ locus HlA antigens. Phenotype frequencies of class II HLA antigens
      were determined in both investigated groups and were used for calculating
      relative risk (RR). If RR was higher than 1, we calculated the population
      attributable risk (EF), and if RR was lower than 1, we calculated the preventive
      fraction (PF). Investigation of statistically significant differences in
      frequencies of class II HLA antigens in patients and control group was performed
      by using chi 2 test. RESULTS: Results of investigation showed that values of RR
      were higher than 1 for HLA DR4 (2,808), DR10 (1,116) and DQ3 (1,386), while we
      noticed a statistically significant difference in frequencies of HLA DR4 (chi 2
      test: 4,805) in patients regarding control group. HLA DQ1 antigen has a
      preventive role in development of IDDM due to highest value of PF (0,314).
      CONCLUSION: Results of our investigation confirm that there is an association of
      HLA DR4 with IDDM in population of Vojvodina. High values of relative risk of
      IDDM, noticed in persons with HLA-DR4 antigen, point to the degree of risk of
      IDDM, which is a disease with great socioeconomic importance in Vojvodina.

PMID- 12793184
TI  - [Amnionic infusion therapy in conditions with low amnionic fluid levels].
AB  - INTRODUCTION: Amniotic fluid volume reduction can have serious consequences:
      prior to 24 gestational weeks hypoplasia of fetal lungs and later in pregnancy
      cord compression and fetal hypoxia as well as contractions of extremities.
      Diagnosis of oligohydramnios is made either after a subjective estimation of
      amniotic fluid reduction or if the biggest amniotic fluid pocket is less than 1
      cm. Amnioinfusion is a procedure during which a crystalloid solution, most often
      saline, is instilled into the amniotic cavity substituting amniotic fluid. To
      estimate the efficacy and safety of amnioinsfusion using our results and
      literature review. MATERIAL AND METHODS: Up to 800 ml of sterile saline solution
      was instilled intraamniotically (10-15 ml/min) in cases where the amniotic fluid
      index was less than 10 and intraamniotic infection was excluded. After that, 1 g
      of Longaceph was given intraamniotically. Infusion was stopped immediately when
      800 ml was instilled, if a subjective estimation showed that there was enough
      fluid or if contractions occurred. RESULTS: During a six-month period there were
      five amnioinfusions--four therapeutical and one diagnostic; in four cases the
      procedure was successful and in one preterm rupture of membranes occurred 20
      hours after the procedure. The procedure was most often done in the first half of
      the third trimester and continuation of pregnancy in successful cases was between
      4 and 5 weeks, with average fetal weight gain of about 1200 gr. No complications
      occurred in cases where pregnancy continued. CONCLUSION: In our preliminary study
      amnioinfusion led to prolongation of pregnancy in majority of cases providing
      better maturation of fetal lungs and higher birth weight, without any
      complications. Further studies are necessary to reach definite conclusions about
      the efficacy and safety of amnioinfusion.

PMID- 12793185
TI  - [New physiologic aspects of fracture healing].
AB  - INTRODUCTION: Skeletal system has a great regenerative potential, but it isn't
      the case with other tissues. Bone fracture healing includes a complex cascade of
      processes at cellular and biochemical levels, ending with a complete structural
      and functional restoration of the damaged bone. Impaired healing occurs in 5-10%
      of all fractures, manifesting as delayed union or non-union. Such a high
      incidence of impaired healing certainly presents a problem, and therefore,
      permanent research regarding physiology of fracture healing is justified. PHASES
      OF FRACTURE HEALING: In this paper we described four phases of fracture healing.
      They are not clearly separated, but overlap. These data are based on contemporary
      literature and newest achievements in the field of fracture healing. DISCUSSION:
      Many data regarding this phenomenon were obtained from animal studies, but they
      may also be applied in human medicine, since there is a great similarity between
      fracture healing in animal models and humans. CONCLUSION: Full and complete
      knowledge of mechanisms of bioregulation of normal fracture healing process
      certainly presents the basic prerequisite for successful surgical and orthopedic
      treatment.

PMID- 12793186
TI  - [Compositae dermatitis].
AB  - INTRODUCTION: Compositae dermatitis is an allergic contact dermatitis caused by
      plant species of the Compositae family. The first report of a cutaneous reaction
      to the Chrysanthemum genus was made by Howe JS in 1887. In 1895 Maiden JH
      reported about skin lesions among men working with Tagetes minuta. Case reports
      of contact allergic-ragweed dermatitis appeared in the American literature as
      early as 1919. The North American feverfew--Parthenium Hysterophorus was brought
      to India from America in 1956 and it caused thousands of cases of so-called
      parthenium dermatitis. Ragweed and parthenium dermatitis became prototypes for
      the classic, so-called "airborne" Compositae dermatitis, that affects primarily
      exposed skin surfaces, and produces a universal erythroderma. EPIDEMIOLOGY: The
      frequency of contact allergy to Compositae in Europe is higher than previously
      believed. It occurs most frequently in middle-aged and elderly persons, but also
      in all age groups. During the two past decades a more equal sex ratio has been
      established. The prevalence varies from 0.7-1.4% in the general population, up to
      4.5% among occupationally exposed persons. Compositae allergy is among the top
      ten contact sensitivities in Europe. In North Europe plants were the cause of
      4.4% cases of occupational allergic contact dermatitis. ETIOLOGY AND
      PATHOGENESIS: Among cultivated Compositae plants, Chrysanthemum is considered to
      be a major sensitizer in Europe (60%). Among the edible types, it is lettuce-
      Lactuca sativa and endive Cichorium endivia (20-30%), and wild-growing feverfew-
      Tanace--tum parthenium (70-90%), tansy--Tanacetum vulgare (54%), and dandelion-
      Taraxacum officinale (65%). Sesquiterpene lactones are the main sensitizers of
      the Compositae family. Other components, thiophenes and acetylenes are said to
      elicit only phytophotodermatitis, but recent studies have demonstrated that some
      thiophenes and benzofuran derivates possess not only phototoxic activity, but
      also sensitizing properties. Photosensitivity is present in 22-75% Compositae
      sensitive individuals. Extracts from Compositae are known to be phototoxic in
      vitro. Photoreactivity of alpha-methylene-gamma-la-ctone group of sesquiterpene
      lactone directed towards the DNA base thymine, thus producing intermolecular 2 +
      2 photoadducts (antigen within the cell), was also thought to be related to
      photosensitivity. Clinical manifestations vary from generalized eczema (20-30%),
      eczema of hands and face (24%), hand (36-44%), or facial eczema (11-28%). 65% of
      patients have vesicular hand eczema. DIAGNOSIS: Routine patch testing with
      sesquiterpene lactone mix, aimed testing with Compositae extracts screening mix,
      Compositae plants, and with their extracts, whereas the treatment of choice is a
      specific allergen-immunotherapy.

PMID- 12793187
TI  - [Role and importance of dietary polyunsaturated fatty acids in the prevention and
      therapy of atherosclerosis].
AB  - INTRODUCTION: Hyperlipoproteinemia is a key factor in development of
      atherosclerosis, whereas regression of atherosclerosis mostly depends on
      decreasing the plasma level of total and LDL-cholesterol. Many studies have
      reported the hypocholesterolemic effect of linolenic acid. TYPES OF
      POLYUNSATURATED FATTY ACIDS (PUFA): Linoleic and alpha-linolenic acids are
      essential fatty acids. The main sources of linoleic acid are vegetable seeds and
      of alpha-linolenic acid-green parts of plants. alpha-linolenic acid is converted
      to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into
      arachidonic acid competing with eicosapentaenoic acid in the starting point for
      synthesis of eicosanoids, which are strong regulators of cell functions and as
      such, very important in physiology and pathophysiology of cardiovascular system.
      Eicosanoids derived from eicosapentaneoic acid have different biological
      properties in regard to those derived from arachidonic acid, i.e. their global
      effects result in decreased vasoconstriction, platelet aggregation and leukocyte
      toxicity. ROLE AND SIGNIFICANT OF PUFA: The n-6 to n-3 ratio of polyunsaturated
      fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is
      a major issue. Traditional western diets present absolute or relative deficiency
      of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and
      fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and
      processed vegetable oils change the nature of polyunsaturated fatty acids and
      obtained derivates have atherogenic properties.

PMID- 12793188
TI  - [Food allergy in children--part I: pathogenesis and diagnostic approach].
AB  - INTRODUCTION: Food allergy is a form of adverse food reaction to different
      nutritive agents caused by immunological mechanisms. This condition is frequent
      in individuals with genetic predisposition. Frequency of food allergies in
      childhood varies in general population from 0.3-7.5%. Characteristics of neonatal
      and infant gastrointestinal tracts are described, as well as the role of
      gastrointestinal tract's immunological immaturity in development of food
      sensitivity. PATHOGENESIS: Features of physical and immunological barriers of
      gastrointestinal tract are described as well as their role in physiological
      conditions, in digestion and absorption of foreign proteins and prevention of
      foreign agents penetration and potentially dangerous proteins into the systemic
      circulation. Gastrointestinal-associated lymphoid tissue (GALT) is the basic part
      of immunological barrier. Its first role is to induce oral tolerance. In normal
      conditions cytokins induce T cells towards Th2 response and also promote
      synthesis of IgA antibodies. Pathogenic mechanisms in evolution of reaginic
      hypersensibility in cases of chronic inflammation are also described.
      Pathological status of gama/delta T cells plays an important role in this
      process, resulting in loss of oral tolerance and development of sensibilitivity.
      CONCLUSION: Diagnostic procedures are multiple and complex. They consist of
      detailed history taking, clinical findings, in vitro and in vivo tests,
      endoscopy, elimination diets and oral provocation tests. Food allergy in
      childhood is often transient and resolves spontaneously.

PMID- 12793189
TI  - [Unilateral laryngeal paralysis].
AB  - INTRODUCTION: Phoniatric rehabilitation is mainly aimed at restoring satisfactory
      phonation. Voice quality depends on the capacity of intact vocal cords to
      compensate the deficiency involved, as well as on automatism of phonation.
      MATERIAL AND METHODS: The study included 50 patients. All subjects underwent
      history taking, reported symptoms that urged them to visit a phoniatrician; they
      were submitted to a clinical otorhinolaryngologic and phoniatric examinations,
      voice assessment by subjective acoustic analysis, spectral analysis by digital
      sonography and laryngostroboscopy. All patients underwent Seeman's method of
      laryngeal compression. RESULTS: The examined group of 50 subjects included 17
      males (34%) and 33 females (66%). Vocal cord palsy was most often due to neck
      surgery (strumectomy) in 19 patients (38%), followed by an idiopathic palsy
      involved in 12 patients (24%). Disocclusion of 1-2 mm and 3-3 mm was registered
      in 54% and 24% patients, respectively. After treatment total occlusion was
      established in 20% of patients, while disocclusion of up to 1 mm, 1-2 mm or 2-3
      mm persisted in 36%, 20% and 2% of patients, respectively. T-test revealed a
      statistically significant difference in glottic incompetence prior to and after
      treatment (p < 0.01). After treatment, using Seeman's method of digital
      compression of the larynx, 48% of patients regained satisfactory speech and voice
      clarity and 50% of them still presented mild dysphonia. Moderate dysphonia was
      registered in 2%, but none of the patients had severe dysphonia. DISCUSSION:
      Central laryngeal palsies made 4% of our examined group, while according to the
      literature they make 1.2-8.7% of all laryngeal palsies. In majority of cases,
      paralysis of the recurrent laryngeal nerve was due to neck surgery (38%), but
      literature reports indicate that iatrogenic palsies are mostly due to operation
      of the thyroid. The well known fact that the left recurrent nerve is more
      frequently paralysed, has been confirmed in our study as well. CONCLUSION:
      Accurate and efficient treatment of unilateral laryngeal palsies requires team
      work. Phoniatric rehabilitation of the disorder using Seeman's method has proved
      efficient in diminishing the glottic incompetence and dysphonia. Patients who
      fail to respond to phoniatric rehabilitation should be treated using other
      therapeutic modalities.

PMID- 12793191
TI  - [Strategies for endoscopic and surgical treatment of biliary tract calculi].
AB  - INTRODUCTION: Common bile duct calculi represent a pathologic entity involving
      obstructive icterus, cholangitis, hepatic cirrhosis or pancreatitits. Common bile
      duct calculi mostly have a secondary origin (from gallbladder) in 95% of cases,
      while primary choledocholithiasis is rare. CLASSIFICATION: From surgical aspect,
      common bile duct calculi can be: 1. Asymptomatic, without manifested symptoms or
      signs, 2. Mobile, with intermittent biliar obstruction and disobstruction, 3.
      Fixed, with obstruction and signs of hepato-biliary and/or bilio-pancreatic duct,
      4. Transitory, microcalculi which pass through Vater's Papilla by propulsion into
      duodenum with symptoms. DISCUSSION: Modern biliary surgery includes diagnosis of
      common bile duct calculi, and if possible preoperative endoscopic (endoluminal)
      surgery, which is less invasive for patients. If such approach is not possible,
      it is necessary to perform stone extraction and cholecystectomy. CONCLUSION:
      Common bile duct calculi represent a common disease of the digestive system.
      Endoscopic diagnostic procedure is very important in management of
      choledocholithiasis. Endoscopic treatment of common bile duct calculi prior to
      cholecystectomy is a method of choice and a strategy for associated cholecysto
      choledocholithiasis.

PMID- 12793190
TI  - [Biochemical and sonographic values in early pregnancy in women with a history of
      early spontaneous abortion].
AB  - INTRODUCTION: The aim of this study was to examine interconnections between
      changes in serum levels of biochemical parameters during pregnancy and
      sonographic parameters relevant for evaluation of early pregnancy. MATERIAL AND
      METHODS: We analyzed serum levels of human chorionic gonadotropin (hCG),
      estradiol (E2), progesterone (PRG) and prolactin (PRL) using ELISA method, in
      cases of complicated pregnancies with symptoms of imminent miscarriage, and in
      patients with uncomplicated pregnancies. We evaluated their impact on mean
      gestational sac diameter (MSD), crown-rump length (CRL), inner diameter of the
      vitelline sac (SV), trophoblast (Trf) thickness and embryonic heart rate (STP).
      All results were correlated using Pearson's test and regression. RESULTS: Changes
      in biochemical parameters of pregnancy correlate significantly with dimensions of
      analyzed sonographic parameters. DISCUSSION: Levels of chorionic gonadrotropin
      affect production of ovarian and placental steroidogenesis. Interrelations were
      also discussed. CONCLUSION: Changes in biochemical values of pregnancy hormones
      affect dimensions of analyzed sonographic parameters. During uncomplicated
      pregnancy, levels of chorionic gonadotropin, progesterone and estradiol affect
      mean gestation-sac diameter, embryo length, depth of trophoblast invasion and
      formation and function of vitelline sac, and thus they alter the embryonic heart
      rate.

PMID- 12793193
TI  - Off-pump myocardial revascularization using the Octopus tissue stabilizer system.
AB  - Off-pump coronary artery bypass surgery (OPCAB) has changed the approach to
      contemporary coronary surgery. Development of new surgical devices and techniques
      has reduced morbidity and mortality during off-pump surgery. From March 2000
      April 2002, a total of 136 patients underwent open heart surgery using off-pump
      technique and fast-track anesthesia at Dedinje Cardiovascular Institute. Octopus
      Medtronic coronary stabilizer was used for stabilization of targeted vessel.
      Arterial grafts were used 169 times and saphenous vein 69 times. Average number
      of anastomoses was 1,830,73 per patient. One patient (0.74%) died. Three patients
      (2.21%) underwent surgery revision due to postoperative bleeding and one (0.74%)
      because of graft dysfunction. Perioperative myocardial infarction was registered
      2 times (1.47%), pneumothorax 3 times (2.21%), postoperative arrhythmias 11 times
      (8.09%), transitory ischemic attack once (0.74%) and deep wound infection once
      (0.74%). Twelve patients (8.82%) required prolonged inotropic support.
      Angiographies early revealed patent grafts in 8 patients (5.88%). OPCAB is a safe
      and effective alternative approach to coronary artery revascularization. Use of
      coronary stabilizer has improved the safety and quality of OPCAB surgery.

PMID- 12793192
TI  - [Suicide risk in patients with depression].
AB  - INTRODUCTION: The purpose of this study was to examine the suicidal risk in
      regard to suicidal thoughts, ideas and attempts among delusional and non
      delusional depressed patients. MATERIAL AND METHODS: 35 non-delusional and 30
      delusional depressed patients were examined. All patients were hospitalized at
      the Psychiatric Clinic in Novi Sad, between 1995-2001. In regard to statistical
      methods t-test and multivariate discriminant analysis were used. RESULTS:
      Delusional depressives were older. They presented greater scores both on Hamilton
      Depressive Rating Scale and Beck Scale of Suicidal Thoughts. They were also at
      greater suicidal risk measured by Suicidal Risk Scale (M.Biro). However,
      delusional depressive patients plan suicide more carefully than non-delusional.
      DISCUSSION AND CONCLUSION: Patients with self-accusing ideas commit suicide most
      frequently. Delusional depressive patients were at higher suicidal risk; their
      suicidal thoughts were more intensive than in non-delusional patients; similar
      results were found in other articles as well.

PMID- 12793194
TI  - [Pulmonary thromboembolism and deep venous thrombosis in the antiphospholipid
      syndrome--case report].
AB  - INTRODUCTION: Systemic lupus erythematosus is a multisystemic disease of unknown
      etiology with diverse clinical symptoms depending on the organ affected. Plasma
      of affected patients contains a specific anticoagulant called lupus
      anticoagulant. It is an antibody which belongs to the class of antiphospholipid
      antibodies which bind to phospolipid-binding proteins, molecules of natural
      coagulation inhibitors, thus increasing the risk of thrombosis. Systemic lupus
      erythematosus commonly affects the skin, joints, serosa, hematopoietic tissue,
      kidneys and the nervous system. Pulmonary symptoms may manifest as pleurisy,
      pneumonia, chronic interstitial pulmonary disease, but pulmonary thromboembolism
      is the most common pulmonary manifestation. CASE REPORT: This is a case report of
      a young female patient who has been suffering from systemic lupus erythematosus
      for twenty years. She was treated for superficial thrombophlebitis for several
      times. She was admitted to our hospital a year before, when she developed
      pulmonary thromboembolism following deep venous thrombosis of the right leg,
      although at that time she was treated by oral anticoagulants. She was discharged
      from hospital with vena cava filter placement and further anticoagulant
      treatment. In a one year period she was hospitalized again due to relapse
      pulmonary of thromboembolism. DISCUSSION: Thrombotic complications in systemic
      lupus are more frequent in patients with antiphospholipid antibodies. Prevention
      of thrombotic complications by anticoagulant agents in patients who already
      developed thrombotic manifestations is considered necessary. CONCLUSION:
      Anticoagulant treatment should be, for preventive reasons, introduced in all
      patients with a systemic disease and with anticoagulant factor, even if they
      haven't developed a thrombotic attack and they should undergo prothrombin time
      measurements and INR: 3-4.

PMID- 12793195
TI  - [Primary lymphoma of the small intestine].
AB  - INTRODUCTION: Small bowel neoplasms are relatively rare, considering digestive
      system neoplasms. The aim of this case report was to point to clinical
      manifestations, significance and treatment patterns of small bowel lymphomas.
      MATERIAL AND METHODS: This is a case report of a sixty-eight year old patient who
      had undergone surgical treatment due to clinical and radiological findings of
      small bowel obstruction. RESULTS: Histological findings revealed a malignant
      lymphoma. Primary small intestine lymphomas are treated by radiochemotherapy
      followed by surgical treatment (partial resection).

PMID- 12793196
TI  - [Internal medicine today and directors of its development].

PMID- 12793197
TI  - Self-renewal and differentiation of hematopoietic stem cells: a molecular
      approach (a review).
AB  - Two characteristics define a hematopoietic stem cell: the ability to
      differentiate into all hematopoietic lineages, and the ability to maintain
      hematopoiesis over a life span by a self-renewal process. The mechanisms that
      regulate the fate of blood-forming cells in vivo, however, are poorly understood.
      Despite the ability to culture hematopoietic progenitor cells (committed to
      particular lineages), in vitro culture of self-renewing multipotent stem cells
      has not yet been achieved. What is clear that both intrinsic and extrinsic
      signals regulate hematopoietic stem cell fate and some of these signals have now
      been identified. which will be highlighted in this review.

PMID- 12793199
TI  - The role of HLA-DRB1*04 alleles and their association with HLA-DQB genes in
      genetic susceptibility to rheumatoid arthritis in Hungarian patients.
AB  - We investigated the HLA-DRB, and DQB polymorphism and haplotypes in RA subjects
      of Hungarian origin by PCR typing using sequence-specific primers. Molecular
      subtyping of HLA-DRB1*04 alleles in RA patients showed strongest association with
      highest relative risk with DRB1*0404. A significantly decreased frequency of
      DRB1*0403 was observed in patients compared to controls. A significant number of
      patients carried DR4 haplotypes on DQB1*0302 (54%) relative to DQB1*0301 which
      was present on 36% of the haplotypes. When compared to controls, the frequency
      was higher in the latter allele only. Few unique DRB-DQB haplotypes were observed
      in Hungarian RA patients. In spite of the fact, that the Hungarian population has
      been isolated linguistically over centuries, a considerable racial admixture has
      occurred following immigration and invasions, thus the present study confirms in
      Hungarian patients with RA, previous findings for RA and HLA in European
      countries.

PMID- 12793198
TI  - Screening adenoviruses in stool samples: evaluation of a genus-specific
      monoclonal antibody based enzyme immunoassay.
AB  - To screen fecal samples for adenovirus antigens a genus-specific monoclonal
      antibody based enzyme immunoassay was developed. In a comparative analysis with
      commercial latex agglutination test, high sensitivity was demonstrated. The assay
      did not detect other viruses usually found in faeces suggesting its specificity.
      One hundred and eighty stool samples collected in Baranya County were tested and
      13 (7.2%) of them showed reactivity. The application of our immunoassay combined
      with other, more sophisticated methods may help us to determine the serotype
      specificity of these adenovirus isolates and assess the importance of
      adenoviruses in viral gastroenteritis.

PMID- 12793200
TI  - Phenothiazines in treatment of HIV infection (a review).

PMID- 12793202
TI  - Autolysis and ageing of Penicillium chrysogenum under carbon starvation:
      respiration and glucose oxidase production.
AB  - During the exponential growth phase of Penicillium chrysogenum NCAIM 00237 the
      effective conversion of glucose and O2 to gluconate and H2O2 by glucose oxidase
      (GOX) was the most likely source of intracellular ROS measured. In glucose
      supplemented autolysing cultures, the increased of intracellular ROS
      concentration was attributed to respiration in the absence of any significant GOX
      activity. The induction of GOX and catalase by glucose and H2O2 was clearly age
      dependent in P. chrysogenum. In ageing cryptic growth phase cultures, superoxide
      dismutase and cyanide-resistant respiration were the major elements of
      antioxidative defence but these activities were insufficient to prevent the
      progressive accumulation of ROS and the concomitant decrease in cell vitality.

PMID- 12793203
TI  - Recent advances in mycovirus research.

PMID- 12793201
TI  - Reactivity of new adhesion molecules on lymphocytes from patients with chronic
      graft versus host disease.
AB  - Reaction patterns of the 7th Human Leukocyte Differentiation Antigen Workshop
      blind panel adhesion molecules were studied on CD3/CD4, CD3/CD8, CD3/TCR gamma
      delta double positive T cells from peripheral blood of patients with chronic
      graft versus host disease (n = 8) and healthy controls (n = 4). Reactivity of 14
      adhesion antibodies was tested by three-colour immunophenotyping. The mean
      proportion of CD3+ T cells (69 +/- 19%). CD3/CD8++ (31 +/- 13%) and CD3/TCR gamma
      delta++ (4 +/- 2%) T sub-populations of patients were comparable with the healthy
      controls. However, the mean percentage of CD3/CD4++ T cell subset in patients (14
      +/- 12%) proved to be significantly decreased in comparison with the normal
      control value (34 +/- 16%) presumably due to secondary immunodeficiency. The
      workshop antibodies proved to be reactive with three T cell subsets expressing
      the examined antigens. Based on the results of the adhesion molecule workshop new
      CD categories have been introduced: CD156b as a transmembrane protein, CD167a as
      an epithelial tyrosin kinase receptor, CD168 as a receptor for hyaluronan
      mediated motility (RHAMM) and CD171 as a co-stimulatory adhesion molecule. There
      were significant differences in the expression of the CD167a and CD156b antigens
      on the CD3/CD4++ subset between the samples of patients compared with the
      controls characterizing the CD4+ T lymphocyte subpopulation in chronic graft
      versus host disease.

PMID- 12793204
TI  - Adenain, the adenovirus endoprotease (a review).
AB  - With the possible exception of very simple viruses, most viruses appear to encode
      at least one virus specific endopeptidase. In addition to facilitating the
      orchestrated fragmentation of polyproteins of RNA viruses, these proteolytic
      enzymes may also be involved in the suppression of host protein synthesis, the
      regulation of virus assembly, the egress and subsequent uncoating in another
      cycle of infection of both RNA and DNA viruses. The endopeptidase encoded by
      adenoviruses (AVP or adenain) appears to be involved in several of these
      functions. Most of the literature concerns the protease of human adenovirus type
      2, but there are good reasons to believe that the proteases of other adenovirus
      serotypes will be very similar. For a review see Weber [1,2].

PMID- 12793206
TI  - Restoring function to the injured human spinal cord.
AB  - Of catastrophic traumas to the human body, spinal cord injury (SCI) has least
      benefited innovations arising from the new biology. Since after WW II, the
      "standard of care" for SCI has changed little. The controversial use of high
      dosages of steroids has provided only modest benefit to patients--but not without
      the enhanced risk of mortality. Novel therapies arising from biochemistry and
      genetics have not materialized in over 15 years, and are unlikely to in the
      author's opinion. Instead, appreciation of biophysics and cell physiology in
      controlling nerve injury, growth, regeneration, and function has produced
      innovative clinical approaches now in testing in human spinal cord injury.

PMID- 12793205
TI  - Craniofacial development: the tissue and molecular interactions that control
      development of the head.
AB  - The molecular cascades that control craniofacial development have until recently
      been little understood. The paucity of data that exists has in part been due to
      the complexity of the head, which is the most intricate regions of the body.
      However, the generation of mouse mutants and the identification of gene mutations
      that cause human craniofacial syndromes, together with classical embryological
      approaches in other species, have given significant insight into how the head
      develops. These studies have emphasized how unique the head actually is, with
      each individual part governed by a distinct set of signalling interactions, again
      demonstrating the complexity of this region of the body. This review discussed
      the tissue and molecular interactions that control each region of the head. The
      processes that control neural tube closure together with correct development of
      the skull, midline patterning, neural crest generation and migration, outgrowth,
      patterning, and differentiation of the facial primordia and the branchial arches
      are thus discussed. Defects in these processes result in a number of human
      syndromes such as exencephaly, holoprosencephaly, musculoskeletal dysplasias,
      first arch syndromes such as Riegers and Treacher-Collins syndrome, and neural
      crest dysplasias such as DiGeorge syndrome. Our current knowledge of the genes
      responsible for these human syndromes together with how the head develops, is
      rapidly advancing so that we will soon understand the complex set of molecular
      and tissue interactions that build a head.

PMID- 12793207
TI  - Dimensions of color: creating high-diffusion layers with composite resin.
AB  - The objective of this article is to provide the clinician with fundamental
      principles for achieving success with directly placed composite resin
      restorations in posterior teeth. It describes the adhesive technique and protocol
      for the development of tooth-colored composite restorations in the posterior
      dentition by integrating the concepts of function, form, and color. A case
      presentation demonstrates the anatomical stratification and proper placement of
      tints and opaquers for the development of the direct posterior composite resin
      bonded restoration. Used with an understanding of tooth morphology, restorative
      material selection, color options, and the physical properties of light, these
      techniques allow optimally esthetic restorations to be predictably achieved.

PMID- 12793208
TI  - iBond: the seventh-generation, one-bottle dental bonding agent.
AB  - Dental adhesive systems used for bonding dental resins to enamel and dentin have
      evolved through several "generations," with changes in chemistries, mechanism,
      number of bottles, application technique, and clinical effectiveness. The trend
      in the latest generation of dental bonding systems is to reduce the number of
      components and clinical placement steps. The introduction of iBond, a single
      bottle dental adhesive system, is the latest of the new generation materials, and
      combines etchant, adhesive, and desensitizer in one component. This article will
      show that laboratory test results comparing the bond strength and margin-gap
      sealing of iBond with other latest-generation dental adhesive systems have shown
      similar results.

PMID- 12793209
TI  - Simplified techniques for the placement of stratified polychromatic anterior and
      posterior direct composite restorations.
AB  - Although many tooth-colored indirect restorative materials are available,
      dentists frequently employ direct composite resins as a primary tooth-colored
      restorative material. Direct resin systems that are suited for stratification, or
      layering of various opacities and colors of dental composite, offer dentists the
      opportunity to accurately reproduce natural teeth in ways that rival the
      esthetics of most indirect systems. This article presents a simplified version of
      the classical three-layered technique originally described by Dietschi, and
      demonstrates the application of a recently introduced composite resin system.

PMID- 12793210
TI  - Frequently asked questions about bleaching.
AB  - Nightguard vital bleaching, or at-home bleaching using a 10% carbamide peroxide
      material in a custom-fitted tray, has become the standard for tooth whitening.
      This article answers many of the questions associated with this process, and
      compares the procedure with other whitening options.

PMID- 12793211
TI  - In-office vital tooth bleaching--what do lights add?
AB  - Aqueous hydrogen peroxide (H2O2) has been used clinically at 30% to 35% levels to
      lighten teeth for many years, but the process has required multiple visits. Heat
      and light have been used empirically in attempts to catalyze H2O2 decomposition
      and speed tooth lightening. The contribution of bleaching lights (LumaArch,
      Optilux 500, and Zoom!) to act as catalysts for lightening teeth was studied in
      83 pairs of contralateral anterior maxillary and mandibular teeth on 15 human
      subjects. Split-arch design using centrals, laterals, and canines on one side
      treated with bleach plus light, were compared with contralateral teeth using
      bleach alone. Three researchers trained in the use of the Vitapan 3D-Master Shade
      Guide took shades with independently agreement within 0.5 value-chroma sum 89% of
      the time throughout the study Laboratory tests determined bleach gel chemistry,
      bleach light output, and effects on the bleaches of light alone and heat alone.
      Results showed that the three test lights did not lighten teeth more than their
      bleach gels alone. All teeth lightened to nearly the same degree (1.7 color
      increments), but LumaArch required 60% less time and Zoom! used 1/3 lower H2O2
      concentration. Laboratory tests indicated that the proprietary chemicals mixed
      into each bleach gel just before use acted as catalysts and were probably
      responsible for more rapid lightening produced by LumaArch gel, and need for less
      H2O2 in Zoom! gel. Neither the heat produced by the accessory lights, nor the
      light output itself were responsible for catalytic activity with any of the three
      systems tested. Collectively, the data demonstrate positive effects from chemical
      catalysts added to bleaching gels. No output from any of the lights resulted in
      heat or light that catalyzed the gels.

PMID- 12793212
TI  - Tray whitening: what the evidence shows.
AB  - In recent years, many dental professionals have changed their philosophy
      regarding the use of trays with at-home bleaching regimens. However, facts do not
      change--and successful vital tooth bleaching still occurs only when tooth
      surfaces are in direct contact with the appropriate concentration of active
      whitening agent for a specific amount of time. Because the science of tooth
      whitening is still in its infancy--this article reviews a series of remaining
      questions regarding vital tooth bleaching based on current scientific information
      and research findings on products using trays.

PMID- 12793214
TI  - Over-the-counter tooth-whitening systems.
AB  - Sales of over-the-counter (OTC) tooth-whitening products have increased sharply
      in recent years because of heightened consumer demand for esthetic care, success
      of in-office and professional home bleaching systems, and heavy promotion by
      product manufacturers. All the whitening products contain hydrogen peroxide or
      carbamide peroxide and differ in their mode of delivery. Because tooth whiteners
      are not regulated by the Food and Drug Administration, many retail products have
      not undergone rigorous, objective, clinical testing and hence may be of
      questionable efficacy and safety. OTC tray-based systems in particular must be
      used with caution because ill-fitting trays can lead to soft-tissue injury,
      malocclusion problems, and poor compliance. Non--tray-based systems, including a
      paint-on system and whitening strips, have recently become available. These
      products are inexpensive, convenient, and easy to use, and they represent the
      fastest growing segment of the retail market. Whitening dentifrices comprise
      approximately 50% of OTC tooth whitening products work mainly by abrasion to
      remove superficial stains. With heightened consumer interest in whiter teeth,
      clinicians must become familiar with OTC products to provide optimal solutions
      and treatment to patients.

PMID- 12793213
TI  - Long-term treatment results with nightguard vital bleaching.
AB  - Since its introduction into dentistry in 1989, nightguard vital bleaching has
      been proven to be a simple and safe procedure to lighten discolored teeth.
      Efficacy of the technique is 98% for nontetracycline-stained teeth, and with
      extended treatment time, tetracycline-stained teeth can be expected to lighten in
      at least 86% of cases. Satisfactory retention of the shade change without re
      treatment can be expected in at least 43% at 10 years posttreatment. Side effects
      are usually mild and transient, disappearing within days of treatment completion
      with no long-term sequelae. Participants report that they are glad they went
      through the procedure, and wild recommend the procedure to a friend.

PMID- 12793215
TI  - The safety of peroxide-containing at-home tooth whiteners.
AB  - Scientific data from research conducted during the past decade have demonstrated
      the safety of the dentist-dispensed at-home whiteners containing 10% carbamide
      peroxide. There has been no evidence of systemic adverse effects associated with
      the proper use of these whitening systems. Most commonly observed local adverse
      effects are mild-to-moderate tooth sensitivity and/or gingival irritation, which
      usually do not prevent the patient from completing the whitening treatment. The
      sensitivity and irritation are transient in most cases, and they dissipate when
      the patient discontinues the use of the whitener. There is no evidence of any
      long-term consequences that have resulted from tooth sensitivity and/or gingival
      irritation. However, potential adverse effects may occur from inappropriate
      applications, abuses, or the use of inappropriate products. The risks of using at
      home whiteners without a dentist's involvement, or using formulations with a
      higher peroxide content than recommended, are yet to be determined. To maximize
      benefits while minimizing potential risks, the author advises using at-home tooth
      whiteners under the supervision of a dental professional.

PMID- 12793216
TI  - The adolescent patient: special whitening challenges.
AB  - Vital tooth bleaching has become increasingly popular, even with the adolescent
      patient. Tooth whitening may be performed in adolescent patients with typical
      bleaching agents; with severe discolorations, it may be more appropriate to use
      the microabrasion technique with subsequent bleaching to achieve desirable
      esthetics.

PMID- 12793217
TI  - The value of dentures.
AB  - Dentures may be boring, but they are a major part of dentistry, and will be for
      the foreseeable future. While implants are growing in popularity, there will
      always be patients who opt for dentures. It is your duty to inform patients of
      the need to have their dentures remade periodically, to ensure excellent oral
      care. Be sure to manage patient expectation and to create an effective system for
      prompt payment. This will enable you to help patients achieve good oral health,
      while maximizing your profit.

PMID- 12793218
TI  - Virtual imaging guiding implant surgery.
AB  - This article describes a method for using software, together with a
      prosthetically designed diagnostic stent and computed tomography (CT) imagery, to
      allow the implant team to take advantage of existing osseous structures, while
      avoiding vital anatomy. The technique involves the conversion of a diagnostic
      stent to a surgical guide stent to allow the precise placement of the implants in
      the sites selected by virtual imagery. The process can be accomplished completely
      in-office by the practitioner, with the assistance of his or her local laboratory
      support.

PMID- 12793219
TI  - Immediate loading of dental implants for mandibular prosthesis in edentulous
      mandibles.

PMID- 12793220
TI  - Comparison of clinical efficacy and safety of three professional at-home tooth
      whitening systems.
AB  - A three-cell, randomized, parallel, investigator-blinded clinical trial was
      conducted to compare the efficacy and safety of three professional at-home tooth
      whitening systems, including Crest Professional Whitestrips (6.5% H2O2), Day
      White 2 (7.5% H2O2) and Nite White Excel 2 (16% carbamide peroxide equivalent).
      Ninety subjects were randomly assigned to three groups (30/group). Subjects were
      instructed to use the assigned whitener following the manufacturers'
      instructions. Clinical examinations at baseline, and on days 3, 7, 14, and 18
      (Day White), or 21 (Crest Professional Whitestrips and Nite White) included the
      following parameters: 1) oral tissues; 2) tooth shade by the Vitapan Classical
      shade guide; 3) tooth shade by a chromameter with a jig; and, 4) tooth
      sensitivity and gingival irritation. The results showed significant shade
      reductions with time in all three groups. Nite White resulted in significantly
      greater shade reductions in periods between days 7, 14, or 21 and baseline than
      did the other two systems. Tooth sensitivity and gingival irritation, which were
      mostly mild and transient, occurred in all groups. It is concluded that all three
      whitening systems evaluated are effective and safe. Nite White Excel is superior
      to the other two systems because it provides a greater whitening efficacy with
      comparable or lower incidence of tooth sensitivity and gingival irritation.

PMID- 12793221
TI  - Has dentistry moved into the nanotechnology era?

PMID- 12793222
TI  - Diagnostic templates for implant treatment planning.

PMID- 12793223
TI  - Reality check.

PMID- 12793224
TI  - Malcolm's mission.

PMID- 12793225
TI  - The American health insurance landscape.

PMID- 12793226
TI  - A clinic closes.

PMID- 12793227
TI  - Psychiatry in China.

PMID- 12793228
TI  - Saving the marriage.

PMID- 12793229
TI  - Carving out care.

PMID- 12793230
TI  - Mapping a road to the future. An update from the National Institute of Health
      Policy.

PMID- 12793231
TI  - Laparoscopic gastric fundoplication for treatment of gastroesophageal reflux
      disease (GERD). Results from 150 consecutive cases.
AB  - Gastroesophageal reflux disease (GERD) is common and often not adequately managed
      with lifestyle changes and medication. Laparoscopic gastric fundoplication has
      widely been accepted as the mainstay in surgical treatment for patients who fail
      medical management. We present a review of 150 consecutive patients with symptoms
      of failed medical management of GERD who were operated on at a community
      hospital. Patients received either a 360 degrees wrap (Nissen Fundoplication) or
      a 270 degrees wrap (Toupet) and, if warranted, a repair of a hiatal hernia.
      Thirty-nine percent of the patients were discharged on the first postop day, and
      another 47% were discharged on the second postop day. Heartburn and coughing were
      completely eliminated in 90% of patients and reduced to a level that was well
      tolerated in all but three patients. Some dysphagia, early satiety, and bloating
      were typical in the immediate postop period but were generally minor and improved
      substantially in the first 4 to 8 weeks. Six percent of patients had some
      complication, some severe and requiring reoperation, but all resolved. Eighty
      five percent of the patients stated that the outcomes was either "perfect" or
      "much better." Laparoscopic gastric fundoplication for treatment of chronic GERD
      is an excellent option for patients who have medically uncontrolled reflux
      symptoms.

PMID- 12793232
TI  - Alternative dispute resolution. The court of first resort.

PMID- 12793233
TI  - The winding road to the privacy rule.

PMID- 12793234
TI  - Managing individual rights requirements under HIPAA privacy.

PMID- 12793235
TI  - Another career avenue for HIM: coding compliance.

PMID- 12793236
TI  - Harnessing the power of e-mail.

PMID- 12793237
TI  - Ready, set, access! An action plan for conducting a HIPPA privacy risk
      assessment.

PMID- 12793238
TI  - Help wanted: privacy officer.

PMID- 12793239
TI  - How HIM adds value to managed care.
AB  - Managed care offers many career opportunities to HIM professionals. If you're
      interested in making a transition to this area, the first step is understanding
      the ways HIM adds value to managed care processes. This article kicks off the
      first in a series on HIM opportunities in managed care.

PMID- 12793240
TI  - Distance learning: getting closer all the time.
AB  - In recent years, distance learning has become an increasingly viable option, and
      HIM students have benefitted. How does this new way of learning work, and is it
      working for students? Some instructors and students tell their success stories.

PMID- 12793241
TI  - Radiology moves to the CPR.

PMID- 12793242
TI  - Systematic approach shortest route to security incidence resolution.

PMID- 12793243
TI  - Practice brief. A HIPAA privacy checklist.

PMID- 12793244
TI  - Practice brief. Facsimile transmission of health information (updated).

PMID- 12793245
TI  - Practice brief. Letters of agreement/contracts (updated).

PMID- 12793246
TI  - Practice brief. Patient photography, videotaping, and other imaging (updated).

PMID- 12793247
TI  - Practice brief. Transfer of patient health information across the continuum
      (updated).

PMID- 12793248
TI  - Coding under the HIPAA Umbrella.

PMID- 12793249
TI  - Electronic antidotes to coding ailments.

PMID- 12793250
TI  - AHIMA advocates for physician query forms.

PMID- 12793252
TI  - How compliance changed healthcare. Hard-line approach to compliance pays off.

PMID- 12793251
TI  - Forms and documentation for HIPAA privacy--a closer look.

PMID- 12793254
TI  - Data transmission: a world of possibilities.

PMID- 12793253
TI  - How compliance changed healthcare. Compliance: a critical, yet costly commitment.

PMID- 12793255
TI  - Working smarter with APCs.
AB  - Are HIM professionals ready to make the most of APCs? This article suggests some
      strategies to improve the way we work with APCs, focus on complete and accurate
      coding, and improve our expertise.

PMID- 12793257
TI  - Trends to watch in home health compliance.

PMID- 12793256
TI  - Six steps to compliance for small practices.
AB  - Developing a compliance plan for a small physician practice can be easier than
      you'd think. The author offers six things HIM professionals can do to ensure a
      practice's compliance.

PMID- 12793258
TI  - Compliance programs: beyond billing and coding.
AB  - Ensuring the success of your compliance program means keeping your eye on more
      than billing and coding. The author highlights some issues on the horizon for
      compliance officers.

PMID- 12793259
TI  - Release of information: the basics.
AB  - Whether you're new to the HIM profession or a long-time expert, release of
      information presents perennial challenges--especially in light of HIPAA. This
      article brings you the basics and the latest updates.

PMID- 12793260
TI  - HCFA, Joint Commission show some restraint.

PMID- 12793261
TI  - Practice brief. Laws and regulations governing the disclosure of health
      information.

PMID- 12793262
TI  - Practice brief. Consent for the use or disclosure of individually identifiable
      health information.

PMID- 12793263
TI  - Practice brief. Notice of information practices.

PMID- 12793264
TI  - Practice brief. Patient anonymity (updated).

PMID- 12793265
TI  - Practice brief. Patient access and amendment to health records.

PMID- 12793266
TI  - Practice brief. Release of information for marketing or fund-raising purposes.

PMID- 12793267
TI  - Taking time to make time.

PMID- 12793268
TI  - Covering the bases of coding compliance.

PMID- 12793269
TI  - Spring training for outpatient hospital coding compliance.

PMID- 12793270
TI  - Compliance is everything, everything is compliance.

PMID- 12793273
TI  - Drafting policy on business ethics.

PMID- 12793272
TI  - Documenting your compliance with HIPAA's privacy rule.

PMID- 12793274
TI  - Using ergonomics to keep injury in check.

PMID- 12793275
TI  - HIM professionals and patient safety: how to positively influence change.

PMID- 12793276
TI  - ISO 9001:2000--setting the standard for quality management.
AB  - How will you approach the next quality management initiative? This article offers
      an introduction to the ISO 9001:2000 quality management system standards that can
      be applied to the HIM industry and how these standards can improve your
      department's policies and procedures.

PMID- 12793277
TI  - PEPP: collaborating to improve quality.
AB  - By collecting and analyzing information about Medicare payment errors, PEPP
      initiatives are making a contribution to healthcare quality efforts nationwide.
      Here's how one organization takes a collaborative approach to improving quality.

PMID- 12793278
TI  - 'Quality is job one' for CPHQs.

PMID- 12793279
TI  - Winning "Joint Commission jeopardy": tips for success. Interview by Julie A.
      Brow.

PMID- 12793280
TI  - Getting your arms around HIPAA.

PMID- 12793281
TI  - CPT-5 supports performance measurement, technology.

PMID- 12793282
TI  - Developing facility-specific productivity measures.

PMID- 12793283
TI  - Not what we were in 1928: a new professional definition.

PMID- 12793284
TI  - [Century XXI].

PMID- 12793285
TI  - [Valoration of the FAS in the contralateral testis after unilateral testicular
      torsion. Experimental study in rats].
AB  - The role the FAS and BCL-2 in the apoptosis of testicular cells in the
      contralateral testis after unilateral testicular torsion, was investigated. We
      compared with control group. These experiments were performed in male Wistar rats
      prepuberal old. FAS and BCL-2 determination is realized in cells cultures of
      contralateral testis. Flow cytometry and immunohistochemistry studies, using a
      FAS and BCL-2 specific monoclonal antibody, were utilized to value FAS y BCL-2
      expression on testiculaires cells following unilateral testicular torsion. We
      observed an increase of expression of FAS and decrease of BCL-2 in the
      contralateral testis in comparison with control group. The present results may
      indicate that the expression of this molecules is implicated in cellular
      apoptosis.

PMID- 12793286
TI  - [Fetal skin allografts on newborn excisional wounds].
AB  - There is clinical and experimental evidence that skin allografts improve
      secondary intention wound healing, however the grafts do not take. Because of the
      special characteristics of the healing process in the fetal period, fetal skin
      allografts could be presumed to be a good alternative to adult skin allografts,
      and even to autografts in particular cases. In order to explore the behavior of
      fetal skin grafts on newborn animals, skin has been grafted to laboratory rabbits
      of two different ages: 26 fetal skin allografts to fetuses and newborns and 21
      neonatal skin allografts to newborns. Macroscopic and microscopic features of the
      grafted area have been compared at the 7th, 14th and 21st postoperative days. The
      newborn response to a fetal skin graft was somewhat different from that to a
      newborn skin allograft, the first showing an earlier increase in graft bed
      vascularization, less edema and less foreign body reaction.

PMID- 12793287
TI  - [Evolution of conservative treatment in traumatic spleen injuries. Report of 54
      cases].
AB  - The spleen is the organ most frequently affected in abdominal trauma.
      Conservative treatment of traumatic spleen injuries is already generally
      accepted, avoiding surgery whenever possible. We present a wide serie (54 cases)
      of traumatic spleen injuries along a period of ten years (1990-2000) during which
      83% of these were solved with conservative therapy we analyse our treatment
      procedure and post-treatment follow-up of these patients.

PMID- 12793288
TI  - [Apoptosis in the cryptorchidism. Role of the FAS protein in it's modulation].
AB  - The cellular degeneration, present at the criptorchidism leads to a malfunction
      in the spermatogenosis and it's due to cellular apoptosis (programed cellular
      death). This process is turned on and modulated by different ways. One of then is
      mediated by Ag-Ac reactions and a protein called FAS seems to have an important
      role in it's modulation. We studied the relation between FAS an the increased
      apoptosis in undescended testics. Testicular biopsies were done in criptorchid
      patients during orchidopexy and FAS was measured by immune-techniques. Our
      results seem to dismiss FAS as a modulation apoptosis factor in the
      cryptorchidism.

PMID- 12793289
TI  - [Incidence of bacterial translocation in four different models of experimental
      short bowel syndrome].
AB  - The outcome of patients with short bowel syndrome is influenced for factors such
      as the length of remnant intestine or the presence or absence of ileocecal valve
      (ICV). Gram-negative sepsis, the main cause of mortality in this group of
      children, is probably due to bacterial translocation (BT), because after gut
      resection there are a number of circumstances that favour its occurrence, being
      the most known intestinal dismotility, bacterial overgrowth, loss of gut
      associated lymphoid tissue, total parenteral nutrition (TPN) and fasting related
      mucosal atrophy. The aim of this experimental controlled study was to test the
      incidence of BT after four different types of gut resection, in animals fed
      orally or receiving TPN. Hundred and three adult Wistar rats bred and raised in
      our facilities according to European Union Regulations were randomly divided in
      six groups:--Group 1 (n = 26): non-manipulated animals, served as a control.-
      Group 2 (n = 14): 80% non-lethal small bowel resection, fed orally.--Group 3 (n =
      15): same resection as group 2 but including ICV. Rat chow ad libitum.--Group 4
      (n = 27): non-resected fasting animals receiving all-in-one TPN solution.--Group
      5 (n = 11): same resection as group 2, but fasting and receiving TPN--Group 6 (n
      = 10): 90% small bowel resection, including cecum and ICV, fasting and TPN. The
      animals were maintained for 10 days in individual metabolic cages, and, at the
      end of the experiment, were bled by portal and cardiac puncture. Mesenteric lymph
      nodes, peripheral and portal blood samples were cultured for BT. Non-manipulated
      rats (group 1) had lower BT incidence (8%) than resected ones (groups 2, 3, 5 and
      6, 93%, 60%, 91%, 60%, p < 0.05) or animals non-resected, receiving TPN (group
      4.51%, p < 0.05). When resection included ICV in orally fed rats BT index was
      also lower (group 3 vs group 2.60% vs 91%, p < 0.05). In TPN resected animals a
      drop was also found in BT when ICV and cecum were added to small bowel resection
      (group 6 vs group 5.60% vs 91%, p < 0.05). IN CONCLUSION: 1. Gut resection is
      associated to a high degree of BT, even if the animals are fed orally. 2.
      Resection including ICV, produced less BT. 3. TPN-related BT was shown in half of
      the animals non resected. 4. TPN-resected rats had also less BT when ICV and
      cecum were removed.

PMID- 12793290
TI  - [Thyroid carcinoma:Experience 57 cases. Is there a different bio-development in
      pediatric age?].
AB  - It has been suggested a different biodevelopment in the differentiated thyroid
      cancer in pediatric age. General and pediatric surgeons from different centres
      has coincided to operate this kind of pediatric pathology that finally conclude
      the treatment in the nuclear medicine department from the reference hospital. The
      objectives of this revision is, to confirm de difference in thyroid cancer in
      pediatric age and to know few factors implicated. MATERIALS AND METHODS: A review
      of 57 patients with differentiated thyroid cancer, medullary and anaplastic were
      excluded, treated in the nuclear medicine department during the last 20 years.
      28% were < 10 years old (16 cases) and 72% > 10 years old (41 cases). This 57
      young patients were operated in 22 hospitals and 79% by a general surgeon and 21%
      by pediatric surgeon. The analysis was performed with SPSS MS Windows 6.0 (chi
      cuadrado, t-Student-Fisher). RESULTS: There are more reinterventions in patients
      operated by a general surgeon. There aren't differences between the number of
      total neck dissections between both groups of surgeons, but when is performed,
      the incidence of complications is significantly high. In patients < 10 years old,
      there are more metastasis and more surgical complications. In spite of, all
      patients still alive. CONCLUSIONS: Children < 10 years old, the illness is more
      local aggressive and the recurrence and lung metastasis is high, more surgical
      complications. We recommend to concentrate this pathology in a few hospitals to
      achieve more experience and to avoid complications.

PMID- 12793291
TI  - [Post-surgical paediatric pain: Nursing- PCA vs continuous I.V. infusion of
      tramadol ].
AB  - AIM: To evaluate the efficiency in the control of the post-surgical paediatric
      pain of the combination of a weak opioid [tramadol (T)] and an NSAID
      (paracetamol), comparing its administration through "Nursing-PCA" (NCA)
      techniques or through continuous i.v. infusion. METHODS: The investigation has
      been carried out in 30 patients (mean 9.5 months) selected according to their
      foreseeable degree of moderate-hard pain. All of them consumed in the
      postoperative period: rectal paracetamol (20 mg/Kg) every 8 hours and tramadol in
      two groups. Group I: PCA pump with tramadol that was handled by the nurse.
      Initial dose: 0.5 mg/Kg NCA, bolus injection 0.3 mg/Kg with an interval of 10
      minutes for security and a highest dose of 1.2 mg/Kg/4 h every 4 hours. Group II:
      continuous infusion i.v. of tramadol (6 mg/Kg/24 h). The pain was evaluated, as
      well as the sedative action, saturation oxygen, respiratory and hemodynamics
      parameters, adverse effects, and efficiency during the first 24 hours, as well as
      the number of total dose of drugs asked in the Nursing PCA group. RESULTS: Pain
      decreased in both groups. There were more sedative effects in group II and the
      total dose of tramadol was higher. There were no cases of respiratory depression.
      CONCLUSIONS: The combination of tramadol and paracetamol through "Nursing PCA"
      has turned out to be an efficient method in the treatment of the post-surgical
      pain in little children and those whose are in their lacteal period. It is a
      possible alternative of the continuous infusion of Morphine in these patients.

PMID- 12793292
TI  - [Laparoscopic treatment for gastroesophageal reflux in children].
AB  - Since 1998 we have operated 5 patients with gastroesophageal reflux (GER) by
      laparoscopic procedure, aged between 6 and 16 years. In the 3 smaller patients we
      have done the Boix-Ochoa antireflux technique. In the other 2 patients we have
      done the Nissen fundoplicature. At 3 months of postoperative course, the 24 hours
      pHmetry is normal in all the patients. They also refer the absence of
      symptomatology of vomiting and/or pyrosis. In 3 patients we could do a
      postoperative manometry of the distal esophagic sphincter, with normal values.
      The postoperative dysphagia of the first seems to be lesser in the group treated
      with the Boix-Ochoa technique.

PMID- 12793293
TI  - [Is laparoscopic surgery the technique of choice in nephrectomy?].
AB  - Laparoscopic is performed in adults for the treatment of benign renal diseases.
      It is widely accepted that laparoscopic surgery has more advantages than open
      surgery in many procedures such as nephrectomy, but there is no further
      experience in this technique. In pediatric urology laparoscopy has become an
      accepted approach for varicocele, non palpable testis, bladder augmentation,
      adrenalectomy and urinary diversion. We report our experience with 25
      laparoscopic nephrectomies in children.

PMID- 12793294
TI  - [Neonatal asymptomatic and childhood symptomatic hydronephrosis: Are they
      different nosological entities?].
AB  - The authors reviewed two groups of patients with ureteropelvic junction
      obstruction divided by age and mode of presentation: patients with neonatal
      asymptomatic hydronephrosis diagnosed by prenatal ultrasonography and patients
      with symptomatic hydronephrosis. It was assumed that in these patients we are
      observing a continuous spectrum of the same pathology; nevertheless, some
      relevant differences were found between the two groups. Diuretic renograms did
      not show any change in postoperative renal function among prenatally detected
      cases while a significative improvement followed surgery among most of
      symptomatic cases. A possible explanation could be found in the obstructive
      mechanism which was responsible of obstruction in a significative proportion of
      these patients. Lower polar vessels produce a progressive symptomatic
      hydronephrosis in an healthy kidney in respect to intrinsic obstruction which are
      mainly found among prenatally detected cases and which are frequently associated
      to congenital renal damage unresponsive to surgery.

PMID- 12793295
TI  - [First orthotopic liver transplantation in patient with biliary atresia and situs
      inversus in spain].
AB  - Biliary atresia is the most common indication for liver transplantation in the
      pediatric age group. The Kasai portoenterostomy has become established as the
      primary treatment for biliary atresia. If portoenterostomy fails, death before 2
      years of age is likely without liver transplantation. The most common multiple
      malformation syndrome associated with biliary atresia is polysplenia syndrome,
      which forms a constellation of defects of body symmetry, splenic development and
      vascular anomalies, including situs inversus, polysplenia and others. The situs
      inversus was formerly considered an absolute contraindication for liver
      transplantation. Recently however, several case reports have been published
      suggesting that neither situs inversus nor this particular subset of vascular
      abnormalities should be considered contraindications to liver transplantation. We
      present one case of liver transplantation performed in patient with biliary
      atresia, situs inversus and polysplenia. This is the first report described in
      Spain for a liver transplant in a child with biliary atresia plus situs inversus.

PMID- 12793296
TI  - [Perineal canal].
AB  - The malformation, perineal canal, is a rare condition accounting for the 4% of
      all anorectal malformations. We report a 15 months old female that presented
      passage of feces per vagina during a diarrheal disease. Former physical exam did
      not show any fistulous opening, another exam under sedation and radiological
      study with barium leaded to the diagnose of perineal canal. The fistula was
      excised without preceding colostomy. After surgery the patient did well without
      complications. Several diagnostic techniques and surgical approaches are
      analyzed. The authors believe that the surgical procedure used in this patient
      have had good outcome and the advantage of no needing of preceding colostomy.

PMID- 12793297
TI  - [About of the retirement].

PMID- 12793298
TI  - Why do PCTs leave midwives out in the cold?

PMID- 12793299
TI  - Children who soil: guidelines for good practice.
AB  - The need for a more coherent and integrated national service for children with
      constipation and soiling has been recognised for some years. It became clear to
      the team at the voluntary organisation Enuresis Resource & Information Centre
      (ERIC) as a result of the experiences of the many parents and professionals who
      contacted them. They responded by setting up a multidisciplinary working group to
      begin the process of reviewing the research. The group then went on to oversee
      the publication of the first national minimum standard guidelines for service
      delivery in this area of child health.

PMID- 12793300
TI  - Health and fitness series--2. Dental decay and the case for fluoride.
AB  - A former Chief Dental Officer explains the use of fluoride in preventing dental
      caries. He discusses the causes and process of dental caries and the basic health
      education messages to communicate to the public. Although the incidence of dental
      caries has reduced in the UK, mainly due to greater use of fluoride, decay
      remains prevalent among socially and economically disadvantaged groups. Dental
      health promotion is also needed for young parents who, having good teeth
      themselves, do not always realise that their children are still at risk of
      caries. Parents are not always aware of how to prevent dental caries in their
      children.

PMID- 12793301
TI  - Occupational therapy and physiotherapy for children with disabilities.
AB  - The aim of paediatric occupational therapy and physiotherapy is to minimise the
      impact of impairments on the child and to enhance the overall quality of life for
      the child and the family. In this article a physiotherapist and an occupational
      therapist outline the settings for therapy, including schools, the assessment of
      child and family and the goals and process of treatment. They also outline the
      particular role of each therapy.

PMID- 12793302
TI  - "Mad for Fitness": an exercise group to combat a high incidence of postnatal
      depression.
AB  - Health visitors working in a socially and economically deprived area of the
      Wirral, Merseyside wanted to find innovative ways to address the high incidence
      of postnatal depression in their caseloads. Believing that exercise may have a
      beneficial effect on depression, they set up a project to make fitness activities
      more affordable and available to their client base. After an initial survey of
      local mothers had indicated support, a pilot "swim, gym and creche" scheme was
      set up in a Leisure Centre in partnership with other agencies. The response from
      the pilot group was positive and suggested that the participants were benefiting
      mentally and physically from the exercise and the social aspects of the group.
      Parents began to take a greater part in running the group and funding was
      obtained to continue the scheme. Further evaluation is in progress and there are
      plans to replicate the scheme in other areas of the local Primary Care Trust.

PMID- 12793303
TI  - Tackling poor parenting: a public health issue.
AB  - The adverse consequences associated with poor parenting persist down the
      generations and are a problem for society as well as individuals. The author
      cites evidence suggesting that in many cases poor parenting is associated with
      socioeconomic deprivation, including health inequalities. She argues that most
      parents (especially mothers, as the main child carers) are motivated to do their
      best for their children but that many families struggle against poverty. Poor
      parenting skills may be a product of poverty and social exclusion rather than the
      fault of individual parents. A public health approach, based on partnership with
      parents to meet their expressed needs in appropriate ways, could offer a
      constructive way forward.

PMID- 12793304
TI  - Genetic counseling and prenatal diagnosis in India--experience at Sir Ganga Ram
      Hospital.
AB  - The experiences in genetic counseling and prenatal diagnosis at a tertiary
      genetic center in India are described. Of 3500 subjects provided genetic
      counseling 28.7% were for prenatal diagnosis, 13.7% for mental retardation +/-
      malformations, 11.5% for thalassemia, hemophilia and leukemia, 8.5% for neural
      tube defects and other malformations, and 8% for muscle dystrophy and spinal
      muscle atrophy. Chromosomal studies in blood (n = 5459) were for recurrent
      abortions (57.8%), delayed milestones (14.7%), malformations (11%), and
      infertility and amenorrhea (10.2%). Indications for amniotic fluid studies (n =
      835) were advanced maternal age (35.7%), high risk result on triple test (21.3%),
      previous child with trisomy 21 (21.3%) and abnormalities seen on ultrasound
      (11.1%). Molecular studies were mostly for thalassemia (843, 24.3%), Duchenne
      muscular dystrophy (443, 12.5%), fragile X syndrome (367, 10.3%), spinal muscular
      atrophy (315, 8.9%), thrombophilia profile (233, 6.6%), triplet repeat disorders
      spinocerebellar ataxias, Huntington disease and Friedreich ataxia-162 (4.6%),
      cystic fibrosis 140 (3.9%) and mitochondrial disorders 101 (2.9%). Other
      disorders for which molecular diagnosis was done were intrauterine infections by
      PCR on the amniotic fluid, Prader Willi/Angelman syndromes, hemophilia,
      achondroplasia, congenital adrenal hyperplasia, and Apert syndrome etc. In
      biochemical studies triple marker tests were the most common (3239), followed by
      aminoacid chromatography (774). Among neurolipidosis metachromatic leukodystrophy
      was the commonest, followed by Krabbe's disease, Tay Sach disease and Gaucher
      disease. Of the mucopolysacharidoses Hurler syndrome was the commonest, followed
      by Hunter syndrome. These data are compared with previous studies and a change
      towards increased prenatal diagnostic tests is observed. The commonest indication
      for amniocentesis has changed to advanced maternal age. CONCLUSION: Advanced
      molecular, cytogenetic and biochemical techniques have been a useful addition for
      genetic counseling and prenatal diagnosis in India.

PMID- 12793306
TI  - Retinopathy of prematurity in VLBW and extreme LBW babies.
AB  - OBJECTIVE: This is a hospital-based, prospective clinical study to determine the
      incidence, risk factors, and outcome of extreme low birth weight and very low
      birth weight pre-term babies with retinopathy of prematurity (ROP) at the Sultan
      Qaboos University Hospital, Oman. METHODS: All babies with a birth weight =/<
      1500 g and gestational age =/< 32 weeks admitted in the Neonatal Unit, were
      screened for ROP between 4 to 6 weeks of age and staged according to the
      international classification and were followed up until complete vascularization
      of the retina. Fifty nine babies formed the study group. RESULTS: The overall
      incidence of ROP was 25.4% (15 out of 59), of which 6 babies had severe ROP and
      underwent cryotherapy/laser. All babies with ROP had a birth weight < 1250 g and
      were born before 31 weeks of gestation. CONCLUSION: ROP is a multifactorial
      disease, the immature retina of the pre-term baby being the primary factor.
      Incidence and severity was inversely proportional to birth weight and gestational
      age. Multiple logistic regression analysis showed that sepsis and total
      parenteral nutrition to be highly significant risk factors. Repeated blood
      transfusions, hypotension and congenital heart disease with left to right shunt
      were seen to be considerably associated with the development of ROP. A decrease
      in overall incidence and severity of ROP was observed in this study.

PMID- 12793305
TI  - Prevalence of iron, vitamin A, and iodine deficiencies amongst adolescent
      pregnant mothers.
AB  - OBJECTIVE: The present study was undertaken to assess the prevalence of iron,
      vitamin A and iodine deficiencies amongst rural Adolescent Pregnant Mothers
      (APM). METHODS: Survey was conducted amongst APM in a rural block; district Udham
      Singh Nagar, Uttaranchal State. In the district, all blocks were enlisted and one
      block was randomly selected. Further, villages in the block were listed (n = 64)
      and five villages were randomly selected for the detailed study. All APM residing
      in the selected villages were included for the detailed study. The data on socio
      demographic parameters was collected utilizing a pre-tested semi-structured
      questionnaire. Anaemia was assessed by hemoglobin estimation with the help of the
      HemoCue instrument. Vitamin-A deficiency (VAD) was assessed by presence of night
      blindness utilizing a pre-tested semi structured proforma. Iodine Deficiency was
      assessed by the clinical examination of the thyroid gland and estimating the
      Urinary Iodine Excretion (UIE) levels of each subject. Nutrient intake was
      assessed by the 24-hr dietary recall method. RESULTS: One hundred and fifty one
      APM, belonging to low socio economic group, were selected for the study. The
      occupation of the families was farming, but the APM were housewives. The mean age
      of the APM was 17.8 +/- 1.5 yr. Eighty nine percent of the APM were in the age
      group 16-19 yr. Sixty percent of the APM were in the gestational age of 24 weeks
      and more. It was found that 46.0% of the APM were anaemic (Hb < 11.0 gm/dl).
      Sixteen percent of the study subjects had presence of night blindness. Fifteen
      percent of the subjects had Goiter. Median UIE level in the subjects studied was
      95.0 micrograms/l. Concomitant prevalence of the three deficiencies was amongst
      2.0% of the population. The 24-hour dietary intake revealed that the mean
      consumption of retinol and iron was only 13 and 28% of the recommended dietary
      allowance, respectively. CONCLUSION: The findings of the present study indicated
      that Anaemia, Vitamin A, and Iodine deficiency existed as public health problems
      in the APM of the study area.

PMID- 12793307
TI  - Microalbuminuria as a predictor of early glomerular injury in children with
      sickle cell disease.
AB  - OBJECTIVE: A cross sectional study was carried out to determine the prevalence of
      microalbuminuria in the pediatric patients with sickle cell disease. METHODS: The
      study was carried out on 64 pediatric patients aged less than 14 years with
      documented HbSS, HbAS and HbS beta thalassemia, Microalbuminuria was estimated
      using single radial immuno diffusion technique. Majority of the study subjects
      were of HbSS type. 38.5% had symptoms for > 2 years. 18.8% of the study
      population had significant microalbuminuria (19.2% of SS type and 18.8% of Hb AS
      types). RESULT: Microalbuminuria excretion was significantly more in patients > 9
      years of age as compared to young patients (p < 0.05). Mean serum creatinine
      levels did not show any significant difference in the various study groups.
      CONCLUSION: Microalbuminuria estimation is a very important clinical marker of
      preclinical glomerular damage in patients with sickle cell disease. It estimation
      would help in the early detection of such patients and prompt initiation of
      therapy.

PMID- 12793308
TI  - Neonatal hyperbilirubinemia and its association with thyroid hormone levels and
      urinary iodine excretion.
AB  - OBJECTIVE: To investigate, if, urinary iodine contents as a marker of iodine
      deficiency and hypothyroidism are associated with the incidence of neonatal
      hyperbilirubinemia. METHODS: One hundred neonates with total serum bilirubin > or
      = 15 mg/dl and with no known cause of jaundice were included in the study as a
      jaundice group. An equal number (n = 100) of non-jaundiced neonates (bilirubin <
      or = 14.9 mg/dl) with matching for age, gestation period and weight were enrolled
      in the study as a control group. RESULTS: Thirteen neonates (13%) in the study
      group had urinary iodine levels < 100 mg/dl as against only 2 (2%) in the control
      group (p < 0.05). Thirty-four (34/200-17%) neonates i.e. 17 each in the study and
      control groups had serum TSH > 5 mU/ml and hence an indirect indicator of iodine
      deficiency in the study population. The mean serum levels of total T3, T4 and TSH
      in the study neonates were 1.52 +/- 1.23 ng/ml, 15.8 +/- 12.0 micrograms/dl &
      3.13 +/- 3.0 mU/ml respectively and did not differ significantly from the mean
      levels in the control group. Only one neonate in the study group had serum TSH >
      20 mU/ml which was suggestive of hypothyroidism, but had normal T3 & T4. Seven
      neonates in the study group and 8 in the control group had low T4. There was no
      significant correlation between the maternal and neonatal urine iodine levels,
      thyroid functions and the bilirubin levels (p > 0.01). CONCLUSION: The jaundiced
      babies had lower urine oidine levels than the control population. Since, there
      was no significant difference in the levels of the thyroid hormones, no cause and
      effect relationship could be inferred between iodine deficiency and jaundice.

PMID- 12793309
TI  - Magnetic resonance spectroscopy in pediatric neurology.
AB  - In the last three decades a range of non-invasive biophysical techniques have
      been developed, of which Magnetic Resonance (MR) has proved to be the most
      versatile. Its non-invasive and safe nature has made it the most important
      diagnostic and research tool in clinical medicine. MR Spectroscopy (MRS) is the
      only technique in clinical medicine that provides non-invasive access to living
      chemistry in situ. This article focuses mainly on proton MRS in brain and also
      phosphorus MRS in calf muscle, with particular reference to the pediatric
      population, the normal spectrum and its use in various disease conditions in the
      practice of pediatric neurology. Few representative case studies among different
      disease groups have also been detailed.

PMID- 12793310
TI  - Cord blood from collection to expansion: feasibility in a regional blood bank.
AB  - This article reviews the various aspect of the experimental phase preceding the
      establishment of an umbilical cord blood (UCB) bank within a regular blood bank,
      a situation totally different from that of de novo establishing a cord blood bank
      having human and financial resources. An ethically approved two-year study has
      been conducted to determine the technical feasibility, and the practical problems
      that might be encountered such as public compliance, the additional workload,
      introduction of new activities ranging from collection and processing to
      progenitor expansion, infectious disease testing, development of a quality
      control system, record keeping and documentation, development of specific
      procedures and definitions of requirements. The cost benefit aspect, which will
      ultimately depend on the frequency of units release, was not considered in this
      study.

PMID- 12793311
TI  - Neurocysticercosis--New Millennium, ancient disease and unending debate.
AB  - A spurt of cases of Neurocysticercosis (NCC) at our department reopened the
      debate on whether to treat or not and spurred us on to review the available
      literature for a viable solution. Despite the disease having been around for
      centuries a cogent treatment plan eludes us even as other ancient scources have
      been successfully engaged. Neurocysticercosis presents a peculiar problem as it
      is an end-stage infection, accidental in man, with a benign natural course and
      would have merited considerably less attention, had it not chosen to infest the
      brain. These unique and characteristic features are the fundamental reasons why
      so many different treatment strategies are continuously proffered; many or none
      seem to work, depending on the viewpoint. And the target organs of this otherwise
      unglamorous tapeworm cyst--the brain, eye and spinal cord-ensure that there is
      always pressure, and temptation to treat rather than let it be, even if the
      weight of evidence is to the contrary. An overview of the history of the disease
      and the most recent happenings is presented here, in which these issues are
      reviewed with special attention to the debate on treatment. From the facts that
      emerge, an attempt has been made to present a workable plan that would help
      practicing pediatricians in treating most encountered cases till such time we
      hear the last word on the issue.

PMID- 12793312
TI  - Achalasia--alacrima--ACTH insensitivity syndrome (Triple A syndrome).
AB  - Triple A syndrome is characterized by achalasia of the cardia, alacrima,
      adrenocorticotrophic hormone (ACTH) resistant adrenal insufficiency and
      progressive neurological abnormalities including autonomic nervous dysfunction.
      An 8-year-old girl presented to the pediatric intensive care unit with sudden
      loss of consciousness and was diagnosed subsequently to have this condition. The
      authors present this condition since it is easily treatable and can be fatal if
      undiagnosed.

PMID- 12793313
TI  - Triple A syndrome--diagnostic and management issues.
AB  - The authors present a family with three children affected with triple A syndrome-
      one had died, one was saved by diagnosis and timely therapy, and one was born
      after the diagnosis in the second child. The gene for the syndrome has been
      cloned and genetic counseling should be offered to these families.

PMID- 12793314
TI  - Growth hormone treatment in a girl with Prader Willi syndrome.
AB  - Prader Willi syndrome (PWS) is a rare endocrine-metabolic disorder that is
      characterised by neonatal hypotonia, hyperphagia, marked obesity, short stature,
      hypogonadism and behavioural problems. 7-20% percent of these children develop
      diabetes mellitus. A large number of individuals with PWS show growth hormone
      (GH) deficiency. Recent studies indicate beneficial effects of GH replacement
      therapy not only for their linear growth but also for correction of metabolic
      dysfunction. In the present communication this article details about the
      therapeutic outcome in a girl with PWS who received recombinant growth hormone
      (rGH), Genotropin. Some carry-over therapeutic benefits have been observed even
      after discontinuation of rGH.

PMID- 12793315
TI  - Iniencephaly.
AB  - Iniencephaly is a rare congenital anomaly which is a type of neural tube defect.
      Babies with iniencephaly are almost always still born but exceptionally live born
      cases are reported. This article reports a case of a live born iniencephalic baby
      who died about 15 minutes after birth.

PMID- 12793317
TI  - Spontaneous regression of retinopathy of prematurity.

PMID- 12793316
TI  - Accidental dextropropoxyphene poisoning.
AB  - Dextropropoxyphene poisoning is an uncommon accidental poisoning in children.
      Presentation is similar to narcotic over dosage or poisoning. Convulsions,
      conduction disturbances, arrhythmias and hypoglycemia are common. Naloxone is the
      antidote. As it is uncommon and not documented in children in Indian literature
      we are reporting this case.

PMID- 12793318
TI  - Challenging patients' personal, cultural, and religious beliefs.

PMID- 12793319
TI  - Bringing moral order to the ordinary: outpatient ethics takes shape.

PMID- 12793320
TI  - Outpatient ethics: "and the walls came tumbling down".

PMID- 12793321
TI  - Medical errors in the outpatient setting: ethics in practice.

PMID- 12793322
TI  - Keeping the patient in the loop: ethical issues in outpatient referral and
      consultation.

PMID- 12793323
TI  - Doubling the guard: ethics and law at the privacy gate.

PMID- 12793324
TI  - Ethical considerations of genetic testing.

PMID- 12793325
TI  - Ethical considerations of electronic communication in the clinical outpatient
      setting.

PMID- 12793326
TI  - Moral distress and the nurse practitioner.

PMID- 12793327
TI  - Enhanced listening skills: gifts from the Hmong.

PMID- 12793328
TI  - Factors that predict better informed consent.

PMID- 12793330
TI  - Practicing accountability in professional ethics.

PMID- 12793329
TI  - Quality improvement and ethics: performance improvement in an oncology practice.

PMID- 12793331
TI  - Outside outpatient ethics: is it ethical for physicians to serve Ringside?

PMID- 12793332
TI  - Does everything cause cancer? No, but 228 human carcinogens may.

PMID- 12793333
TI  - Human papillomavirus and cervical cancer: not just a sexually transmitted
      disease.
AB  - The human papillomavirus (HPV) is the cause of virtually all cancers of the
      cervix, the fourth most common cancer in women in the United States. HPV is
      sexually transmitted, and the lifetime risk of contracting the virus is estimated
      to be 75%-90%. New methods of detecting HPV infection and cellular changes
      (dysplasia) caused by HPV can greatly reduce the mortality associated with this
      virus. More than 100 types of HPV exist and may be classified as low-,
      intermediate-, or high-risk in terms of causing cancer. The virus can cause
      genital warts, subclinical dysplasia, and cancer. Nurses play an important role
      in educating patients regarding HPV and preventive measures as well as in
      screening and treatment. Most women diagnosed with HPV need emotional support and
      factual information provided in a supportive, nonjudgmental manner. Nurses can
      meet this challenge and make a difference in reducing the incidence and mortality
      of cervical cancer.

PMID- 12793334
TI  - Depression in patients with advanced cancer.
AB  - Sadness is a normal reaction to the fears, anxieties, and uncertainties during
      any stage of cancer but is especially problematic during the advanced stage.
      Depressive symptoms and syndromes frequently coexist during this time and affect
      quality of life. Depression is an overlooked and undertreated symptom during late
      stage cancer. This article provides an overview of the epidemiology,
      neurophysiology, diagnostic and screening approaches, risk factors, and treatment
      modalities for depression in patients with advanced cancer.

PMID- 12793335
TI  - Central venous catheter site care for blood and marrow transplant recipients.
AB  - Treatment-induced neutropenia, long central venous catheter (CVC) dwell times,
      and the use of immunosuppressive agents place blood and marrow transplant
      recipients at high risk for CVC infection. The most common causative organisms of
      CVC infection are ubiquitous skin flora of hospitalized patients. A great deal of
      research on CVC care, including dressing change procedures and frequency, has
      been conducted; however, variations in study design, patients studied, and
      terminology used to define CVC infection limit the generalizability of the
      findings. This article reviews significant studies of CVC care and infection
      rates and describes the findings of a survey of CVC care practices of Blood and
      Marrow Stem Cell Transplant Special Interest Group members of the Oncology
      Nursing Society.

PMID- 12793336
TI  - Updating your peripheral neuropathy "know-how".
AB  - Peripheral neuropathy is a condition that can be caused or exacerbated by the
      administration of certain chemotherapeutic agents. The effects of chemotherapy
      induced peripheral neuropathy (CIPN) are dose limiting and might lead to
      permanent, debilitating disabilities. Oncology nurses should be aware of the
      impact of CIPN. Nurses should be cognizant of the pathophysiology, pre-existing
      conditions contributing to an increased risk of CIPN, causative agents, and
      interventions used in managing CIPN. Awareness that the peripheral nervous system
      is divided into small fibers, large fibers, and the autonomic nervous system is
      important in the assessment, detection, and treatment of CIPN. Presenting
      symptoms are related to the specific fibers that are damaged. Because of the
      different mechanisms of action, CIPN symptoms vary depending on the
      chemotherapeutic agents used. This article provides a general overview of CIPN,
      including pathophysiology, causes, risk factors, assessment, and current
      treatment. Oncology nurses must be alert for the manifestations of CIPN. Early
      intervention and patient education can have a positive effect on the quality of
      life for patients with this disorder.

PMID- 12793337
TI  - Hormonal therapy for breast cancer: focus on fulvestrant.
AB  - Fulvestrant, the first drug of the pure estrogen antagonists to be approved for
      clinical use, is a new therapeutic option for metastatic breast cancer.
      Fulvestrant offers a unique metastatic breast cancer treatment option because its
      mechanism of action is the destruction, rather than the blockade, of estrogen
      receptors. No known agonistic activity exists, limiting potential side effects
      and receptor exhaustion. The side effect profile of fulvestrant is related to its
      antiestrogen effect and includes gastrointestinal disturbance, urinary tract
      infection, and vaginitis. Suggestions for managing the side effects of
      fulvestrant are described, and a case study is provided as an illustrative aid in
      understanding the role of this new hormonal agent.

PMID- 12793338
TI  - Ecteinascidin-743.
AB  - Ecteinascidin-743 (ET-743) is a marine-derived antineoplastic agent undergoing
      clinical trials to evaluate its use in the treatment of a variety of solid
      tumors. After the completion of the phase I studies, the agent subsequently was
      investigated in phase II trials for efficacy in a variety of tumor types. Ongoing
      phase I evaluation continues with other antineoplastic agents. Side effects of ET
      743 include myelosuppression, hepatotoxicity, and nausea and vomiting. Liver
      function test monitoring is crucial and useful in predicting other serious
      toxicities. Nursing care issues and patient education are discussed in this
      article.

PMID- 12793340
TI  - Advances in brachytherapy: new approaches to target breast cancer.
AB  - Advances in breast brachytherapy techniques have led to the development of new
      approaches for treatment of patients with early-stage breast cancer. This article
      reviews the indications, clinical utility, and nursing interventions for the
      Mammosite Radiation Therapy System (Proxima Therapeutics, Alpharetta, GA) and
      INTRABEAM (Photoelectron Corporation, North Billerica, MA) radiation therapy
      system. Each uses a slightly different approach to provide definitive
      radiotherapy to the breast tumor bed following excision. Radiation oncology
      nurses should have an understanding of how each system works to provide optimal
      care as it pertains to education, side effect management, and catheter care for
      patients receiving each of these types of radiotherapy. These innovative
      alternatives will greatly reduce required treatment time if clinical studies find
      them to be equivocal or superior to traditional radiation therapy techniques.
      These treatment approaches also may make radiation treatments more convenient for
      women with early-stage breast cancer.

PMID- 12793339
TI  - Agent Orange: management of patients exposed in Vietnam.
AB  - Since the Vietnam War ended in 1975, numerous studies have been conducted to
      determine if an association exists between Agent Orange exposure and certain
      disabling conditions specifically cancer.  Although a definite causal
      relationship has not yet been established, sufficient data associate Agent Orange
      with certain conditions.  Because  of their advancing age similar to other baby
      boomers, Vietnam veterans are at a higher risk of developing malignancies. 
      However, their exposure to Agent Orange also may increase their risk for cancer
      and other associated diseases.  This article examines the latest findings of
      scientific research sponsored by the Department of Veterans Affairs and discusses
      the importance of well-informed oncology nurses when providing care for patients
      with cancer exposed to Agent Orange.

PMID- 12793342
TI  - The use of nebulized fentanyl for the management of dyspnea.

PMID- 12793341
TI  - Nursing assessment and management of dyspneic patients with lung cancer.
AB  - Dyspnea is a subjective sensation of breathlessness. This distressing symptom is
      experienced by many patients with lung cancer and often is accompanied by
      physiologic signs and symptoms, such as tachypnea, tachycardia, pallor, and
      cyanosis. Dyspnea-induced hypoxia may occur and cause confusion, cognitive
      impairment, and restlessness. Prompt and accurate nursing assessment of dyspnea
      can assist in identifying appropriate treatment interventions. Supplemental
      oxygenation and medications, along with treatment of the underlying cause of the
      dyspnea, may promote patient comfort. Nurses need to be skilled in assessing
      dyspnea experienced by patients with lung cancer and knowledgeable in
      implementing effective symptom management techniques.

PMID- 12793343
TI  - Control of pain after breast reconstruction procedure.

PMID- 12793344
TI  - Evidence-based practice and research methodologies: challenges and implications
      for the nursing profession.

PMID- 12793345
TI  - Vascular access device thrombosis.

PMID- 12793346
TI  - Thrombocytopenia.

PMID- 12793348
TI  - A new name, a new look, the services you have come to trust.

PMID- 12793347
TI  - Oxaliplatin: third-generation platinum analog.

PMID- 12793349
TI  - Canadian Hepatitis C Information Centre. CPHA to launch new HepC information
      centre.

PMID- 12793350
TI  - Diabetes mellitus in HIV-infected women.

PMID- 12793351
TI  - Growth failure is important factor in the survival rate of HIV-infected children.

PMID- 12793352
TI  - A clinician's dilemma: diminished capacity in HIV/AIDS patients.

PMID- 12793353
TI  - Dentistry. Complication risks of invasive procedures on HIV+ patients.

PMID- 12793354
TI  - Nursing. How one clinic met a new demand without additional resources.

PMID- 12793355
TI  - Harm reduction, substance use and the immune system.

PMID- 12793362
TI  - Radiation therapy. A valuable treatment tool.

PMID- 12793363
TI  - Health tips. Seasickness.

PMID- 12793364
TI  - SARS--emerging illness causing widespread concern.

PMID- 12793365
TI  - Antioxidant supplements may not help heart health.

PMID- 12793366
TI  - Controlling blood pressure. Cheaper may be better.

PMID- 12793367
TI  - Nuts. Seeds for your health.

PMID- 12793368
TI  - Swollen lymph nodes. What's the cause?

PMID- 12793369
TI  - With the news about West nile virus the past few summers, I'm nervous about
      getting bitten by mosquitoes. What can I do to protect against them?

PMID- 12793370
TI  - The last time my doctor prescribed an antibiotic for me, I ended up with a
      vaginal yeast infection. Do antibiotics cause yeast infections?

PMID- 12793371
TI  - Vision. Changes as you age.

PMID- 12793372
TI  - Final rule on antibiotic drug labeling.

PMID- 12793373
TI  - Wider use of rapid HIV test.

PMID- 12793374
TI  - Lab test rules out heart attack.

PMID- 12793375
TI  - New drug for parasitic infections in children.

PMID- 12793377
TI  - Expanded use of HPV test.

PMID- 12793376
TI  - First biologic treatment approved for psoriasis.

PMID- 12793378
TI  - Safeguards for gene therapy trials.

PMID- 12793379
TI  - Counterfeit Procrit.

PMID- 12793380
TI  - New class of medications approved for advance HIV.

PMID- 12793381
TI  - Skin decontamination lotion cleared for military use.

PMID- 12793382
TI  - Labeling changes for Lindane.

PMID- 12793383
TI  - Contaminated honey seized.

PMID- 12793384
TI  - NCI study: more than 2 million U.S. women could benefit from tamoxifen.

PMID- 12793386
TI  - FDA begins product approval initiative.

PMID- 12793385
TI  - Public health officials caution against ephedra use. Health officials caution
      consumers against using dietary supplements containing ephedra. The stimulant can
      have dangerous effects on the nervous system and heart.

PMID- 12793387
TI  - HHS blueprint to boost breast-feeding.

PMID- 12793388
TI  - Operation Liberty Shield: new food security guidance.

PMID- 12793389
TI  - Strategies to reduce medication errors. How the FDA is working to improve
      medication safety and what you can do to help.

PMID- 12793390
TI  - Cloning: revolution or evolution in animal production?

PMID- 12793391
TI  - Cruising with confidence.

PMID- 12793392
TI  - FDA issues guidance on race and ethnicity data.

PMID- 12793393
TI  - Maryland company guilty of smuggling medical devices.

PMID- 12793394
TI  - Be a partner in your health care.

PMID- 12793395
TI  - Should you worry about the side effects of statins? Statin dose, health, and
      other drugs affect side-effect risk.

PMID- 12793396
TI  - The skinny on obesity and cancer. Obesity increases the risk of death from
      cancer, but being overweight isn't inescapable.

PMID- 12793397
TI  - Group therapy effective for bipolar disorder. Education-based therapy may help
      avert relapses.

PMID- 12793398
TI  - SARS: a moving target.

PMID- 12793399
TI  - Travelers, prepare!

PMID- 12793400
TI  - "Safe" blood lead levels may damage kids' brains.

PMID- 12793401
TI  - Tanning salons for psoriasis?

PMID- 12793402
TI  - Cementing broken spines.

PMID- 12793404
TI  - Shorter hospital stays, especially for elderly.

PMID- 12793403
TI  - Anesthesia alternatives for hernia repair.

PMID- 12793405
TI  - Arthritis drugs boost BP, risk of heart disease.

PMID- 12793406
TI  - Radio waves treat stress incontinence.

PMID- 12793407
TI  - My total prostate-specific antigen (PSA) level is 0.2 nanograms per milliliter,
      which I'm told is normal. But my free-to-total PSA ratio is 8 percent, which I've
      read indicates a high risk of prostate cancer. What do these seemingly
      contradictory PSA results mean?

PMID- 12793408
TI  - What's the best way to deal with a bee or wasp sting?

PMID- 12793409
TI  - Description and time reduction of a Monte Carlo code to simulate propagation of
      polarized light through scattering media.
AB  - Propagation of polarized light through a scattering medium has been studied with
      a Monte Carlo code to obtain polarized backscattered images. Studies of these
      backscattered patterns obtained with polarized illumination can be used as a
      technique to characterize the medium anisotropy factor g. First we present the
      different steps of the Monte Carlo simulation that describe polarized light
      propagation in a turbid medium. Monte Carlo is a good tool to simulate the
      backscattered polarized light but is time-consuming. Therefore, we consider two
      ways to decrease the computation time. The first way deals with angle sampling of
      the light direction. The second takes advantage of backscattered image symmetry
      to divide the simulation time by a factor of 4. By combining these two techniques
      we significantly decrease the code computation time.

PMID- 12793410
TI  - [Antidepressive agents do not reduce the risk of suicide].

PMID- 12793411
TI  - [Older tricyclic antidepressants were potent suicide-agents].

PMID- 12793412
TI  - Long-term mechanical ventricular assistance toward myocardial recovery.
AB  - Myocardial recovery after VAD support provides a perfect example of reverse
      remodeling. It also establishes that heart failure may not be an end of the road
      situation. Although post-LVAD myocardial recovery has become a distinct entity,
      basis of reversal of the dedifferentiation process will need to be further
      explored. With this objective, several centers in the United States have formed
      the LVAD Working Group to: determine the incidence of myocardial recovery; obtain
      serial studies to determine the response of the LVAD-supported heart to stress;
      and study the tissue and serological changes as they relate to the recovery
      process. Patients enrolled in this study will receive anti-heart failure therapy
      and serial examinations after implantation and explanation. Stress evaluations
      will include dobutamine stress echocardiograms as well as bicycle exercise with
      right heart catheterization. A large database of prospectively collected data
      will likely result in a greater understanding of myocardial recovery and the LVAD
      weaning process.

PMID- 12793413
TI  - Ventricular ectopy after exercise as a predictor of death.

PMID- 12793414
TI  - Ventricular ectopy after exercise as a predictor of death.

PMID- 12793415
TI  - Carcinoid heart disease.

PMID- 12793416
TI  - Genetics of colorectal cancer.

PMID- 12793417
TI  - Elective primary cesarean delivery.

PMID- 12793418
TI  - Computer crash.

PMID- 12793419
TI  - Computer crash.

PMID- 12793420
TI  - The Cat Group launches policy statements and website. Policy statement 1: timing
      of neutering.

PMID- 12793421
TI  - Peter Charles Doherty.

PMID- 12793422
TI  - Syphilis: a medical, cultural-historical and philatelic study.

PMID- 12793423
TI  - [Editorial comment: fast track, ultra-fast track or accelerated recovery? A
      typical example of term confusion].

PMID- 12793424
TI  - The biochemical diagnosis of Gitelman disease and the definition of
      "hypocalciuria".

PMID- 12793425
TI  - [Editorial comment: effects of percutaneous transluminal coronary angioplasty on
      left ventricular diastolic function].

PMID- 12793426
TI  - Editorial comment: plasma homocysteine, coronary risk factors and serum nitrite
      in coronary artery disease and vascular syndrome X.

PMID- 12793427
TI  - Agreement reached on global framewok convention on tobacco control.

PMID- 12793428
TI  - [Dentistry versus treatment of the mouth (or monarchy versus republic)].

PMID- 12793429
TI  - [Editorial comment: role of myocardial backscatter analysis in the dilated
      cardiomyopathy].

PMID- 12793430
TI  - [Editorial comment: distribution of therapeutic procedures and drug selection in
      coronary artery disease].

PMID- 12793431
TI  - Editorial comment: outcome of coronary bypass surgery and left ventricular
      dysfunction.

PMID- 12793432
TI  - [Editorial comment: mobile telephones and implantable cardioverter
      defibrillators].

PMID- 12793433
TI  - [Concept of WHO for leprosy therapy].

PMID- 12793434
TI  - Does Australia need a more effective policy of science communication?

PMID- 12793435
TI  - Dietitians and exercise: training and practice.

PMID- 12793436
TI  - [Bourneville's medico-social work].
AB  - Bourneville's disease is well known but his medical social work is particularly
      unrecognised. However, he provoked many shifts in hospital policy, medical and
      paramedical studies, regional organization providing for the welfare of mothers
      to-be and infants. He has been at the avant-garde for the treatment of mental
      illness of infants or children.

PMID- 12793437
TI  - [About the 350th anniversary of the foundation of the chair of anatomy of the
      faculty of medicine at Strasbourg (1652-2002)].
AB  - Some historical and bibliographical elements are given at the occasion of the
      350th anniversary of the foundation of the chair of anatomy at Strasbourg.
      Strasbourg played an important role in the dissemination of the anatomical
      knowledge in the end of the 15th and the first half of the 16th century. In 1517,
      the first official human dissection organized in Strasbourg was performed. In
      1652, a specific chair of anatomy founded, and the first holder was J. A. Sebiz
      (1614-1685). In 1670, an anatomical lecture theatre was created. Strasbourg
      became a French town in 1681 with no modification of the university and of the
      chair of anatomy. In 1872, after the annexation of Alsace, a new German
      university was founded ; normal anatomy and pathology were separated and each
      chair attached to a particular institute. In 1919, when the Faculty of Medicine
      was reorganized after Alsace was restored to France, specific chairs and
      institutes were founded for histology and embryology. Among the famous
      morphologists and scientists who worked in Strasbourg were in anatomy : H.
      Brunschwig (?-1534), W. H. Ryff (c. 1505-1548), J. Winter von Andernach (1497
      1574), T. Lauth (1758-1826), F. D. Reisseissen (1773-1828), J. F. Lobstein (1777
      1835), E. A. Lauth (1803-1837), E. Koeberle (1828-1915), E. Beaunis (1830-1921),
      H. D. Bouchard (1833-1899), J. G. Joessel (1838-1892), W. Waldeyer (1836-1921),
      G. Schwalbe (1844-1916), W. Pfitzner (1853-1903), F. Keibel (1861-1929), A.
      Forster (1878-1957), and P. Bellocq (1888-1962) ; in pathology : F. D. von
      Rechlinghausen (1833-1910), H. Chiari (1851-1916), J. G. Monckeberg (1877-1925),
      P. Masson (1880-1959), and L. Gery (1883-1957) ; in histology : P. Bouin (1870
      1962), M. Aron (1892-1974), R. Courrier (1895-1986), and M. Klein (1905-1975) ;
      in embryology : P. Ancel (1873-1961), P. Vintemberger (1891-1983), J. Benoit
      (1896-1982), E. Wolff (1904-1996), and J. Clavert (1912-1994).

PMID- 12793438
TI  - Repression of TGF-beta signaling by the oncogenic protein SKI in human melanomas:
      consequences for proliferation, survival, and metastasis.
AB  - Transforming growth factor-beta (TGF-beta ) has dual and paradoxical functions as
      a tumor suppressor and promoter of tumor progression and metastasis. TGF-Ji
      mediated growth inhibition is gradually lost during melanoma tumor progression,
      but there are no measurable defects at the receptor level. Furthermore, melanoma
      cells release high levels of TGF-beta to the microenvironment, which upon
      activation induces matrix deposition, angiogenesis, survival, and transition to
      more aggressive phenotypes. The SKI and SnoN protein family associate with and
      repress the activity of Smad2, Smad3, and Smad4, three members of the TGF-fl
      signaling pathway. SKI also facilitates cell-cycle progression by targeting the
      RB pathway by at least two ways: it directly associates with RB and represses its
      activity when expressed at high levels, and indirectly, it represses Smad
      mediated induction of p21(Waf-1) This results in increased CDK2 activity, RB
      phosphorylation,and inactivation. Therefore, high levels of SKI result in lesions
      to the RB pathway in a manner similar to p16 (INK4a) loss. SKI mRNA and protein
      levels dramatically increase during human melanoma tumor progression. In
      addition,the SKI protein shifts from nuclear localization in intraepidermal
      melanoma cells to nuclear and cytoplasmic in invasive and metastatic melanomas.
      Here, I discuss the basis for repression of intracellular TGF-beta signaling by
      SKI, some additional activities of this protein, and propose that by disrupting
      multiple tumor suppressor pathways, SKI functions as a melanoma oncogene.

PMID- 12793439
TI  - [Further study on COPD].

PMID- 12793440
TI  - Extracorporeal shock wave therapy no better than placebo in the treatment of
      plantar fasciitis.

PMID- 12793441
TI  - Work and non-work-related stress increase the risk of arm symptoms.

PMID- 12793442
TI  - Stretching before or after exercising has no effect on muscle soreness or risk of
      injury.

PMID- 12793443
TI  - Traditional Chinese acupuncture does not improve outcomes from post-stroke motor
      rehabilitation.

PMID- 12793444
TI  - [Problems in laboratory diagnosis of tuberculosis].

PMID- 12793445
TI  - Achieving operating room efficiency through process integration.
AB  - As healthcare organizations look for ways to gain new efficiencies and reduce
      costs, they are examining surgical services with a critical eye. In many cases,
      the operating room (OR) was not included in enterprisewide reengineering efforts,
      thereby limiting the positive impact of those efforts. Healthcare organizations
      are recognizing that every point along the patient care continuum is
      interrelated. To truly maximize reengineering efforts, they need to integrate the
      entire process and information flow within the OR and across the enterprise.

PMID- 12793446
TI  - Final security regulations present challenges, opportunities for HIM.

PMID- 12793447
TI  - [Editorial comment: effects of gender on 28 days mortality in acute myocardial
      infarction].

PMID- 12793448
TI  - Finding meaning in a child's violent death: a five-year prospective analysis of
      parents' personal narratives and empirical data.
AB  - Finding meaning in the death of a loved one is thought to be extremely traumatic
      when the circumstances surrounding the death is perceived to be due to
      negligence, is intentional, and when the deceased suffered extreme pain and
      bodily harm immediately prior to death. We addressed this assumption by obtaining
      personal narratives and empirical data from 138 parents 4, 12, 24, and 60 months
      after an adolescent's or young adult child's death by accident, suicide, or
      homicide. Using the Janoff-Bulman and Frantz's (1997) framework of meaning-as
      comprehensibility and meaning-as-significance, the purposes were to identify the
      time course to find meaning, present parents' personal narratives describing
      finding meaning in their experiences, identify predictors of finding meaning, and
      compare parents who found meaning versus those who did not on five health and
      adjustment outcomes. The results showed that by 12 months post death, only 12% of
      the study sample had found meaning in a child's death. By 60 months post death,
      57% of the parents had found meaning but 43% had not. Significant predictors of
      finding meaning 5 years post death were the use of religious coping and support
      group attendance. Parents who attended a bereavement support group were 4 times
      more likely to find meaning than parents who did not attend. Parents who found
      meaning in the deaths of their children reported significantly lower scores on
      mental distress, higher marital satisfaction, and better physical health than
      parents who were unable to find meaning. Recommendations for future research are
      made.

PMID- 12793449
TI  - [Editorial comment: hypertension and ventricular arrhythmias].

PMID- 12793450
TI  - Predictors of bereaved parents' satisfaction with group support: an Israeli
      perspective.
AB  - This study evaluates various aspects of group work with bereaved parents who lost
      a child during military service. More specifically, it assesses the unique and
      cumulative contributions of various features of group work to the participants'
      satisfaction with the group support. One hundred and thirty-eight bereaved
      parents, who participated in 16 support groups, answered a battery of
      questionnaires tapping 3 aspects of the group work: their motives for joining the
      group, the interpersonal relations among the group members, and the group
      leadership style. In addition, the participants were asked to evaluate the
      contribution of the intervention to their adjustment. The findings indicate that
      the supportive elements of the intervention were associated with the groups'
      perceived contribution. The clinical implications of these results are discussed.

PMID- 12793451
TI  - [Editorial comment: relationship of tricuspid annular tissue Doppler with
      pulmonary artery pressure and vascular resistance].

PMID- 12793452
TI  - [Editorial comment: requirements for minimally invasive cardiac surgery].

PMID- 12793453
TI  - Homicide bereavement counseling: a survey of providers.
AB  - The opinions of 116 homicide bereavement caregivers of interventions recommended
      for survivors were solicited. Presenting problems, optimum treatment framework,
      and reasons for treatment failure were also surveyed. Respondents preferred
      methods associated with crisis intervention and grief counseling. Other clinical
      techniques were rated as moderately helpful, except family therapy, which was
      highly rated. Suppression of trauma imagery was deemed harmful to survivors,
      though diversion was recommended often in cases of complicated grief. Caregivers
      who are themselves survivors appeared more sensitive to some of the emotional
      aspects of homicide bereavement, such as the potential for retraumatization in
      therapy.

PMID- 12793454
TI  - The need for improved operational definition of suicide attempts: illustrations
      from the case of street youth.
AB  - The use of inadequate operational definitions of suicidal behavior is often a
      limitation of suicide research. In this article, the results of an exploratory
      qualitative study of street youth suicidality is contrasted with the existing
      literature to highlight the problems associated with defining suicidal behaviors.
      It is argued through the use of the case example of street youth that accurate
      and detailed assessment of suicidal history, context, and intent is necessary to
      avoid substantial threats to the validity and clinical use of research findings.

PMID- 12793456
TI  - [Evidence in otorhinolaryngological surgery--evidence in the treatment of
      idiopathic sudden sensorineural hearing loss].

PMID- 12793455
TI  - Medicare program; prospective payment system for long-term care hospitals: annual
      payment rate updates and policy changes. Final rule.
AB  - This final rule establishes the annual update of the payment rates for the
      Medicare prospective payment system (PPS) for inpatient hospital services
      provided by long-term care hospitals (LTCHs). It also changes the annual period
      for which the rates are effective. The rates will be effective from July 1 to
      June 30 instead of from October 1 through September 30, establishing a "long-term
      care hospital rate year" (LTCH PPS rate year). We also change the publication
      schedule for these updates to allow for an effective date of July 1. The payment
      amounts and factors used to determine the updated Federal rates that are
      described in this final rule have been determined based on this revised LTCH PPS
      rate year. The annual update of the long-term care diagnosis-related groups (LTC
      DRG) classifications and relative weights remains linked to the annual
      adjustments of the acute care hospital inpatient diagnosis-related group system,
      and will continue to be effective each October 1. The outlier threshold for July
      1, 2003, through June 30, 2004, is also derived from the LTCH PPS rate year
      calculations. In addition, we are making an adjustment to the short-stay outlier
      policy for certain LTCHs and a policy change eliminating bed-number restrictions
      for pre-1997 LTCHs that have established satellite facilities and elect to be
      paid 100 percent of the Federal rate or when the LTCH is fully phased-in to 100
      percent of the Federal prospective rate after the transition period.

PMID- 12793457
TI  - Qualitative determination of false-positive effects in the acetylcholinesterase
      assay using thin layer chromatography.
AB  - A method has been developed to determine the false-positive effects on
      acetylcholinesterase inhibition in the TLC assay based on Ellman's method.
      Various aldehydes and amines have been tested in order to determine whether the
      observed inhibition is due to a true enzyme inhibition or due to the inhibition
      of the reaction between thiocholine and 5,5'-dithiobis-(2-nitrobenzoic acid). 4
      Dimethylaminobenzaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, diethylamine,
      triethylamine, triethanolamine and tyramine showed real enzyme inhibition,
      although their activity was about 10(3) times lower than that shown by
      galanthamine. Heptanal, decanal, cinnamaldehyde, anisaldehyde, benzaldehyde,
      hexylamine and tryptamine appeared to show a non-specific chemical inhibition. By
      checking this chemical inhibition on the TLC assay, the true enzyme inhibition
      could be distinguished from the false-positive chemical inhibition observed in
      the toluene extract of Nerine bowdenii in the course of isolation of active
      compounds.

PMID- 12793458
TI  - Determination of diterpenoid triepoxides in Tripterygium wilfordii by micellar
      electrokinetic capillary chromatography.
AB  - A micellar electrokinetic capillary chromatographic (MEKC) method has been
      established for the identification and determination of diterpenoid triepoxides
      in the Chinese herb Tripterygium wilfordii Hook F. and its preparations. Studies
      of the influence of boric acid and borax buffer concentration and pH, and of
      sodium dodecylsulphate (SDS) concentration have been carried out, and the optimum
      separation for the triepoxides was achieved using 20 mM boric acid and 10 mM
      borax with 20 mM SDS as the running buffer. MEKC was found to exhibit good
      accuracy, precision and repeatability. The sensitivity of the assay was
      sufficient to monitor the three active components in T. wilfordii and its
      preparations.

PMID- 12793459
TI  - Chemical and enzymatic hydrolysis of anthraquinone glycosides from madder roots.
AB  - For the production of a commercially useful dye extract from madder, the
      glycoside ruberythric acid has to be hydrolysed to the aglycone alizarin which is
      the main dye component. An intrinsic problem is the simultaneous hydrolysis of
      the glycoside lucidin primeveroside to the unwanted mutagenic aglycone lucidin.
      Madder root was treated with strong acid, strong base or enzymes to convert
      ruberythric acid into alizarin and the anthraquinone compositions of the
      suspensions were analysed by HPLC. A cheap and easy method to hydrolyse
      ruberythric acid in madder root to alizarin without the formation of lucidin
      turned out to be the stirring of dried madder roots in water at room temperature
      for 90 min: this gave a suspension containing pseudopurpurin, munjistin, alizarin
      and nordamnacanthal. Native enzymes are responsible for the hydrolysis, after
      which lucidin is converted to nordamnacanthal by an endogenous oxidase.

PMID- 12793460
TI  - Determining acetylcholinesterase inhibitory activity in plant extracts using a
      fluorimetric flow assay.
AB  - A fluorometric assay for acetylcholinesterase inhibitory activity was developed
      in a flow system using the fluorogenic substrate 7-acetoxy-1-methyl quinolinium
      iodide which is hydrolysed to the highly fluorescent 7-hydroxy-1-methyl
      quinolinium iodide. The detection limit of galanthamine is 0.5 microM, which is
      about 20 times more sensitive than in the colorimetric flow assay. In the
      presence of 30% methanol or of 5% acetonitrile, about 70% of the enzyme activity
      could still be detected. Various plant extracts have been screened using the
      described system including bulbs of Galanthus nivalis, Eucharis amazonica (E. x
      grandiflora), Crinum powelli and Nerine bowdenii (all members of the
      Amaryllidaceae), which showed strong AchE inhibitory activity.

PMID- 12793461
TI  - Purification of anthocyanins from species of Banksia and Acacia using high
      voltage paper electrophoresis.
AB  - A new method has been developed for the isolation and rapid identification of
      anthocyanins from two floricultural crops based on the use of high-voltage paper
      electrophoresis with bisulphite buffer. Using this method, anthocyanin pigments
      were successfully purified as their negatively charged bisulphite-addition
      compounds from crude extracts of plant tissue. In conjunction with liquid
      chromatography-electrospray mass spectrometry, the method enabled the
      anthocyanins from the flowers of two Banksia species and the leaves of two Acacia
      species to be identified. The Banksia flowers contained both cyanidin and
      peonidin-based pigments, while the Acacia leaves contained cyanidin and
      delphinidin derivatives.

PMID- 12793462
TI  - Identification and quantification of methyl jasmonate in leaf volatiles of
      Arabidopsis thaliana using solid-phase microextraction in combination with gas
      chromatography and mass spectrometry.
AB  - Static headspace sampling with solid-phase microextraction has been used in
      combination with GC-FID and GC-MS for the specific enrichment, identification and
      quantification of volatile methyl jasmonate secreted by wounded leaves of
      Arabidopsis thaliana. The microsample method of analysis was found to be precise,
      accurate, sensitive and rapid. The detection limit of the procedure is 1.5 ppb
      (approximately 1.3 ng) per injection, which is of adequate sensitivity to detect
      the natural baseline levels of methyl jasmonate (approximately 10-100 ng/g)
      present in plant tissues. The method can be applied to most plants, requires a
      minimum of sample material, and shows the additional advantage that it is
      suitable for automation and could thus be used for high-throughput screening.

PMID- 12793463
TI  - Determination of manganese (II) in some medicinal plants and their decoctions by
      a kinetic spectrophotometric method.
AB  - The catalytic effect of manganese (II) on the oxidation of the azo dye tropaeolin
      00 with potassium periodate in the presence of 1,10-phenanthroline was
      investigated. The reaction was followed spectrophotometrically by measuring the
      decrease in the absorbance of the azo dye at 445 nm. Under the optimum analytical
      conditions, manganese (II) in the range 0.05-2.5 ng/mL could be determined by the
      fixed-time method with a detection limit of 0.02 ng/mL. The developed method is
      highly sensitive, selective and simple, and was applied successfully to analyse
      decoctions of some medicinal plants for trace amounts of total manganese (II) and
      free manganese (II) ions without separation.

PMID- 12793464
TI  - Supercritical carbon dioxide extraction of colchicine and related alkaloids from
      seeds of Colchicum autumnale L.
AB  - A method for the extraction of the alkaloids colchicine, 3-demethylcolchicine and
      colchicoside from seeds of Colchicum autumnale by supercritical carbon dioxide
      has been established. Several parameters such as pressure, temperature,
      percentage of modifier and extraction time have been examined. Two extraction
      steps with constant carbon dioxide density (0.90 g/mL) and flux (1.5 mL/min) were
      required to extract the alkaloids in 110 min using 3% methanol as modifier. The
      quantitative determination of the alkaloids was performed by HPLC; the
      percentages of recovery were higher than 98% for the three alkaloids. This
      extraction procedure was compared with a conventional method involving maceration
      and sonication, and the same levels of alkaloids were obtained in each case. The
      supercritical carbon dioxide method is, however, very efficient, more rapid and
      more environmentally friendly than conventional methods.

PMID- 12793465
TI  - Electrospray mass spectrometric decomposition of some glucuronic acid-containing
      flavonoid diglycosides.
AB  - Mass spectrometric fragmentation patterns of herbacetin 3-O-glucopyranoside-8-O
      glucuronopyranoside (1), gossypetin 3-O-glucopyranoside-8-O-glucuronopyranoside
      (2) and takakin 7-O-glucopyranoside-8-O-glucuronopyranoside (3) were elucidated
      from mass spectra obtained with electrospray ionisation. The usefulness of the
      fragmentation patterns observed in the positive and negative mode for structural
      elucidation of the studied compounds is discussed. The fragmentation of 3 was
      substantially different from 1 and 2, especially in the negative mode. In order
      to explain these differences, theoretical calculations were performed.

PMID- 12793466
TI  - Ionic content in plant extracts determined by ion chromatography with
      conductivity detection.
AB  - A simple method is described for the determination of the ionic content of
      vegetable samples by ion chromatography with suppressed conductivity detection.
      Extracts of leaves of cucumber (Cucumis sativus), leaves and cotyledons of
      watermelon (Citrullus lanantus), cotyledons of zucchini (Cucurbitapepo), and
      leaves and roots of olive (Olea europaea) obtained at room temperature yielded
      chromatographic profiles with substantial differences in the relative contents of
      Cl-, NO3-, HPO4(2-) and SO4(2-) as well as of Na+, NH4+, K+, Mg2+ and Ca2+.
      Although NO3-, Cl- and K+ were common to each extracted sample and accounted for
      most of the ions present, two additional anion peaks (i.e. malate and oxalate)
      were detected. Among the vegetable tissues investigated, olive roots contained a
      considerable amount of oxalate (37 mg/g dry weight), while Na+, which is present
      in very low amount in extracted samples of leaves and cotyledons, represented ca.
      30% of the cationic content of olive roots. In all the examined tissue extracts,
      K+ was the main cation (16-55 mg/g dry weight) and NO3-, Cl- and HPO4(2-) were
      the main inorganic anions.

PMID- 12793468
TI  - Childhood obesity--why should we be worried?

PMID- 12793469
TI  - Wheeze, eczema and rhinitis in 6-7 year old Irish schoolchildren.
AB  - The aim of this study was to determine the prevalence of wheeze, eczema and
      rhinitis in 6-7 year old schoolchildren in Louth and Meath and assess their risk
      factors. The ISAAC (International Study for Asthma and Allergies in Childhood)
      questionnaire was used. The response rate was 64.1% (n = 1899). The prevalence
      rates for wheeze, eczema and rhinitis were 17.4%, 11.2% and 20.2% respectively,
      with 2.4% of children reported to be suffering from all 3 conditions. The main
      risk factors for wheeze were male sex and smoking in the home. Ninety-five
      (28.7%) children with wheeze had no diagnosis of asthma. Of these children 36
      (37.9%) had wheeze with exercise, 55 (59.9%) had a dry cough not associated with
      a cold or flu and 13 (13.7%) reported more than 4 attacks of wheeze in the last
      year. This study suggests underdiagnosis and undertreatment of atopic illness in
      this age group. It also suggests decreasing exposure to passive smoking and early
      recognition and treatment will improve quality of life for many children.

PMID- 12793470
TI  - Detecting mood disorders in men diagnosed with cancer who seek semen
      cryopreservation: a chance to improve service.
AB  - To assess the prevalence of mood disorders in patients diagnosed with cancer and
      who pursue fertility preservation. Prospective questionnaire. The Human Assisted
      Reproduction (H.A.R.I.) unit, Rotunda Hospital. Twenty nine men were recruited
      between August 2001 and January 2002. Patients were informed about the study and
      requested to sign a consent form prior to completing the Hospital Anxiety and
      Depression Scale (HADS). Information regarding the patients diagnosis and
      prognosis were obtained from a standard referral form completed by the referring
      oncologists. The prevalence of mood disorders and to determine if this is related
      to the pretreatment prognosis. Anxiety was diagnosed in 44.8% and depression in
      17.2% of patients. However clinically significant anxiety and depression was
      diagnosed in 13.8% and 6.9% respectively. There was no significant difference in
      the scores for anxiety and depression in the good prognosis group compared with
      the guarded group. Reduced sperm count was diagnosed in 26.9% of men and
      decreased motility in 30.8%, but neither of these were influenced by mood.
      CONCLUSION: Anxiety and depression are commonly encountered in patients with
      cancer. Most cases are of mild to moderate severity. Knowledge of our patients'
      psychological status will contribute to an improved service.

PMID- 12793471
TI  - Acceptability of antenatal HIV testing in Ireland.
AB  - To assess the acceptability of antenatal HIV testing. A questionnaire based
      study. Obstetric outpatient clinic at the Portiuncula Hospital, Galway, Ireland.
      Women attending the antenatal clinic between May and November 2000. The
      participating women received pamphlets explaining HIV testing in pregnancy before
      completing the questionnaire. The questions included assessment of their views
      towards prenatal HIV testing, perceived benefits and acceptability. Seven hundred
      and forty-eight questionnaires were distributed. Of these 715 (96%) completed
      questionnaires were returned out of which 32 (4.5%) were discarded because they
      were improperly completed. 683 (96%) correctly completed questionnaires were
      analysed. 650 (95.2%) women agreed that prenatal HIV testing was a good idea and
      that test was necessary, 17 (2.5%) said test was not a good idea, 30 (4.4%) said
      test was unnecessary and 16 (2.3%) and 3 (0.4%) women were unsure whether or not
      test was a good idea and necessary respectively. Three hundred and sixty two
      (53%) women were of the opinion that prenatal HIV testing was of benefit to the
      mother and her baby; 301 (44%) to the mother, baby and the health workers; 14
      (2%) to the baby; and 3 (0.4%) only to the mother. Only 3 (0.4%) women reported
      that prenatal HIV testing was of no benefit. The majority of the women, 436
      (63.8%) had second level education, 202 (29.6%) received third level and 45
      (6.6%) had only primary education. Antenatal HIV testing is acceptable to the
      majority of the obstetric population studied.

PMID- 12793472
TI  - Causes of sensitisation in patients awaiting renal transplantation in Ireland.
AB  - Sensitisation to HLA antigens, formed as a result of transfusion, previous
      allografts or pregnancy, remains a significant problem in transplantation. The
      aim of this study was to define the causes of sensitisation of potential renal
      allograft recipients in Ireland in the post-EPO era. A retrospective survey of
      all patients who were active on the renal transplant waiting list during 1996 was
      performed evaluating the panel reactive antibodies (PRA), history of sensitising
      events, and waiting time for transplantation. Of a total of 244 patients (151
      males, 93 females), 163 (67%) were not sensitised (PRA < 10%), and 35 (14%) were
      sensitised (PRA 10-59%), 15 subjects (6%) were significantly sensitised (60-79%)
      and 31 (13%) were highly sensitised (PRA > 80%). Only 59 (24%) patients had no
      sensitising events recorded. Fifty-eight (24%) subjects had previous allografts.
      Transfusion was documented in 173 (71%) subjects. Pregnancy was noted in 55/93
      (59%) female subjects. All highly sensitised patients had been transfused. Eighty
      per cent (12/15) significantly sensitised and 97 (60%) of the non-sensitised
      subjects had been transfused. The level of sensitisation clearly increased with
      the number of units transfused. Non-sensitised subjects received a mean of 5.65
      units (SEM 1.38), sensitised subjects a mean of 9.8 units (SEM 3.17),
      significantly sensitised a men of 18.2 units (SEM 6.51), while highly sensitised
      subjects received a mean of 37.8 units, (SEM 8.4). There was a direct
      relationship between the waiting time for transplantation and the degree of
      sensitisation. The percentage of patients who had been transfused in the 1996
      cohort (71%) was similar to the percentage of patients transfused on the waiting
      list in August 1999 (75%). These data demonstrate that transfusion remains an
      important cause of sensitisation, despite the use of EPO. Measures to further
      reduce the use of transfusion or the use of immunosuppression at the time of
      transfusion in potential allograft recipients may be of value in the future.

PMID- 12793473
TI  - Recurrent aortoenteric fistula.

PMID- 12793474
TI  - Lower limb dysesthesia--an ominous sign in lumbar fractures.
AB  - Attempts at diagnosing dural lacerations secondary to fractures of the lumbar
      vertebrae on plain radiographs has varied considerably. If undiagnosed these
      injuries can cause serious complications. We present a clinical sign not
      previously documented to our knowledge. Plain radiographs in this case failed to
      show significant canal compromise but excessive hip pain, with the limb held in a
      characteristic posture, heralded cauda equina injury in a burst lumbar fracture.
      The limb was held in hip and knee flexion, with resistance to passive extension
      due to lower limb dysesthesia. This sign helped in determining the investigation
      and treatment of our patient.

PMID- 12793475
TI  - Renal cell carcinoma presenting with vaginal metastasis.

PMID- 12793476
TI  - Successful surgical treatment of Moya Moya Syndrome in a child.

PMID- 12793477
TI  - Paralysed by streptokinase.

PMID- 12793478
TI  - Ireland in the World Cup: trauma orthopaedic workloads.
AB  - To determine if whether there were any changes in numbers of orthopaedic injuries
      at the emergency/ orthopaedic trauma department requiring treatment that could be
      related to televised home matches during World Cup 2002. Numbers of patients
      attending with musculoskeletal injuries directly attributable to world cup
      celebrations were collected during the four home matches. Attendances from
      midnight before the match until midday the day after the match were recorded.
      Control groups were matched from the previous month of May, and matched with the
      same day of the week for each of the four groups. Significantly more patients
      were admitted to the trauma service, referred to orthopaedic outpatients, and
      referred to the minor trauma clinic in the match versus control groups. 280
      patients required onward referral during the match period compared with 233
      during the control period. Televised Irish matches during the World Cup
      significantly increased the workload of the trauma orthopaedic service with
      musculoskeletal injuries. This should be taken into account when planning for
      such events in the future.

PMID- 12793479
TI  - Place of death. What is the measure of success?

PMID- 12793480
TI  - Acute psychiatry day hospital referral rates during the World Cup.

PMID- 12793481
TI  - An expensive superstition--'a Saturday flit is a short sit'.

PMID- 12793482
TI  - Continuous bloomers.

PMID- 12793483
TI  - Open reduction and internal fixation of calcaneal fractures with a low profile
      titanium calcaneal perimeter plate.
AB  - Forty-two intra-articular calcaneus fractures underwent open reduction and
      internal fixation with a low profile, titanium plate with a shape similar to the
      lateral aspect of the calcaneus. All 42 fractures healed without complication.
      There were no cases of hardware breakage. None of the patients were noted to have
      a loss of reduction. The plates were applied without bending and molded to the
      side of the calcaneus with tightening of the screws. No patient complained of
      symptomatic hardware during the follow-up period. With postoperative plain
      radiographs, the reduction was judged as anatomic in 35 patients, less than a 2
      mm step off in six patients, and one patient with greater than 2 mm step off. Use
      of this new plate allows for easy application as it does not require contouring,
      is well tolerated without complaints of hardware prominence, and none of the
      hardware broke prior to fracture union.

PMID- 12793484
TI  - Perioperative complications of the Scarf osteotomy.
AB  - We reporting the perioperative complications during our early experience using
      the Scarf osteotomy to correct hallux valgus. A case note review was carried out
      for the first 100 Scarf osteotomy procedures completed by the senior author.
      There were six patients (6%) with perioperative complications. Four of these were
      intraoperative complications including a split first metatarsal in three cases, a
      shearing of the K-wire in one case and there were two cases of postoperative
      stress fracture. These complications should be considered by those beginning to
      master the Scarf osteotomy procedure and by surgeons teaching surgical trainees.

PMID- 12793485
TI  - Salvage technique for treatment of periplafond tibial fractures: the modified
      fibula-pro-tibia procedure.
AB  - We describe a technique of fixation for treatment of distal tibia periplafond
      fractures and nonunions that uses a modification of the principle of the fibula
      pro-tibia procedure (fusing the tibia and fibula together to create a one-bone
      lower leg). The fibula is plated, and the screws are brought across to the medial
      tibial cortex. The procedure is accomplished with or without a tibial buttress
      plate and always includes iliac crest bone grafting of the nonunion site and
      synostosis. We have used this technique in five patients with satisfaction.

PMID- 12793486
TI  - Flexor hallucis longus transfer for chronic Achilles tendonosis.
AB  - A technique similar to the one described by Hansen for reconstruction of chronic
      Achilles tendinosis using the flexor hallucis longus (FHL) tendon was used in 26
      patients (29 tendons). Follow-up on all 26 patients (mean age 51.3 years) is
      provided with an average follow-up 35 months (range, 12 to 58 months). All
      patients were evaluated postoperatively to assess pain, function, and alignment
      of the ankle and hindfoot. The AOFAS Foot Ratios for the ankle and hindfoot
      (total of 100 points) was used. Time to maximum improvement was 8.2 months
      (range, three to 20 months). Ankle-Hindfoot Scale ratings improved from 41.7
      (range, 23 to 63) preoperatively to 90.1 (range, 49 to 100) postoperatively. All
      but three patients evaluated their result as good or excellent in regards to
      improved function and pain. No patient had a significant functional deficit or
      deformity of the hallux after transfer of the FHL tendon.

PMID- 12793487
TI  - The in vivo elastic properties of the plantar fascia during the contact phase of
      walking.
AB  - The in vivo elastic properties of the plantar fascia during the contact phase of
      walking were determined experimentally by integrating a pressure-sensitive
      optical gait platform with a radiographic fluoroscopy system for recording
      skeletal motion. In order to calculate the fascia's tension-deformation relation,
      lateral images of the foot's skeleton that allowed evaluation of the fascia's
      transient length from the arch-contact to toe-off stages of walking were obtained
      simultaneously with the vertical foot-ground contact forces. The plantar fascia
      was shown to undergo continuous elongation from arch-contact to toe-off, reaching
      a deformation of 9 to 12% between these positions. Rapid elongation of the
      fascia, at a strain rate of about 0.9 +/- 0.1 Sec-1, was observed before and
      immediately after midstance, while a significantly slower elongation occurred at
      a strain rate of approximately 0.2 +/- 0.1 Sec-1 around push-off and toe-off. The
      average stiffness of the fascia at the slow-to-moderate walking velocities was
      170 +/- 45 N/mm, which is similar to reported stiffness values for cadaver fascia
      specimens. The present technique may be useful for validation of computational
      models of the soft tissues of the foot as well as for testing the effectiveness
      of orthoses and shoe types for relieving excessive strain of the fascia in the
      treatment of plantar fasciitis.

PMID- 12793488
TI  - The effect of plantar fascia release on strain in the spring and long plantar
      ligaments.
AB  - The effect of plantar fascia release on strain in the spring and long plantar
      ligaments was investigated in 11 cadaveric feet. Strain gauges were placed in the
      spring and long plantar ligaments of each specimen, and cyclic axial loading was
      applied until reproducible hysteresis curves were observed in the ligaments
      before and after plantar fascia release. After release of the plantar fascia, the
      average strain observed in the spring ligaments at 920N of axial load increased
      by 52% (p < .001) and in the long plantar ligaments by 94% (p = .04). Longer
      resting lengths of the ligaments were also observed. Release of the plantar
      fascia significantly changed force distributions in the foot which may explain
      the development of deformities and symptoms observed clinically following this
      procedure.

PMID- 12793489
TI  - The association between diagnosis of plantar fasciitis and Windlass test results.
AB  - Twenty-two patients with plantar fasciitis, 23 patients with other types of foot
      pain, and 30 patients in a control group were evaluated with the Windlass test
      performed in a weightbearing and non-weightbearing position. In the non
      weightbearing test, the first MP joint was maximally dorsiflexed with the ankle
      stabilized. The weightbearing test was performed with the toes hanging off the
      edge of a stool and dorsiflexion of the first MP was performed. Seven of the 22
      patients in the plantar fasciitis group had a positive weightbearing Windlass
      test (31.8%), while only three had a positive test result in a non-weightbearing
      position (13.6%). None of the patients in the other foot pain group or control
      group had pain in the weightbearing and non-weightbearing positions. Despite its
      high rate of specificity, the low rate of sensitivity of the Windlass test may
      limit its usefulness in the clinical evaluation in patients with plantar
      fasciitis.

PMID- 12793490
TI  - The effect of leg length discrepancy on foot loading patterns and contact times.
AB  - The effect of a simulated leg length discrepancy on foot loading patterns and
      gait cycle times in normal individuals was investigated. Thirty feet of 15 normal
      volunteers were evaluated. Leg length discrepancy was simulated using flexible
      polyurethane soles. As leg length discrepancy increased, the total loading
      increased from 35.31 to 37.99 kg/cm2/sec, forefoot loading increased from 15.58
      to 19 kg/cm2/sec, hindfoot loading remained the same. All subjects, except
      females with middle loading patterns, demonstrated increased hallux loading. The
      contact phase of gait decreased from 22% to 13%, the midstance phase remained the
      same, the propulsion phase increased from 44% to 50%. All findings were
      statistically significant. Leg length discrepancy has significant effects on the
      foot. Different adaptive loading patterns amongst subsets of individuals are
      seen.

PMID- 12793491
TI  - Tendon transfer fixation: comparing a tendon to tendon technique vs.
      bioabsorbable interference-fit screw fixation.
AB  - Tendon transfer techniques in the foot and ankle are used for tendon ruptures,
      deformities, and instabilities. This fresh cadaver study compares the tendon
      fixation strength in 10 paired specimens by performing a tendon to tendon
      fixation technique or using 7 x 20-25 mm bioabsorbable interference-fit screw
      tendon fixation technique. Load at failure of the tendon to tendon fixation
      method averaged 279N (Standard Deviation 81N) and the bioabsorbable screw 148N
      (Standard Deviation 72N) [p = 0.0008]. Bioabsorbable interference-fit screws in
      these specimens show decreased fixation strength relative to the traditional
      fixation technique. However, the mean bioabsorbable screw fixation strength of
      148N provides physiologic strength at the tendon-bone interface.

PMID- 12793492
TI  - The main function of ankle braces is to control the joint position before
      landing.
AB  - The aim of the present investigation was to evaluate the stabilizing effect of 10
      different ankle braces during simulated inversion on a tilting platform. Twenty
      five subjects participated in the study (23 +/- 3 yrs, 71 +/- 12 kg, 177 +/- 9
      cm). Ten commercially available ankle braces and a trapdoor in combination with a
      goniometer system that measured hindfoot inversion inside the shoe were used.
      Inversion was subdivided into a free fall and a maximum inversion phase. Results
      showed that all braces restricted inversion significantly between 51% and 15%
      compared to the no-brace condition but distinct differences between models were
      found. Maximum inversion angle and inversion velocity were lower for those braces
      that restricted inversion most effectively during the free fall phase. Reaction
      times of the peroneus longus did not appear to influence the degree of inversion.
      Relatively constant differences between free fall and maximum inversion angles
      for all models (between 6 degrees and 10 degrees) and a high correlation between
      these two parameters suggests that the main function of ankle braces is to
      restrict inversion during the free fall phase and not at the extremes of motion.

PMID- 12793493
TI  - Anticardiolipin antibody associated arterial thrombosis following fibula
      fracture.
AB  - A case is described of a 20-year-old college student in whom open reduction and
      internal fixation of a Weber B fibula fracture was complicated by arterial
      thrombosis and gangrene of the foot. The patient subsequently required a below
      knee amputation. A hypercoagulability workup revealed the presence of an
      anticardiolipin antibody. Although this is an extremely unusual complication,
      young female patients with a positive personal or family history of early
      thrombotic events, such as DVT, multiple pregnancy loss, or early myocardial
      infarction, should be viewed as being at increased risk. Additional risk factors
      such as oral contraceptive use, should be sought during the initial history.

PMID- 12793494
TI  - Evaluation of the Sports Ankle Rating System in young, athletic individuals with
      acute lateral ankle sprains.
AB  - The purpose of this paper is to introduce the Sports Ankle Rating System and
      provide the initial validation for its use. As its name implies, this outcomes
      measurement system is intended for use in assessing the functional outcomes of
      athletes with ankle injuries. This unique system consists of three distinct
      instruments: the Quality of Life Measure, the Clinical Rating Score, and the
      Single Assessment Numeric Evaluation. We began the validation process of the
      Sports Ankle Rating System with subjects who had sustained lateral ankle sprains
      because this is the most common injury in sports. The results of this study
      indicate that the Sports Ankle Rating System is: 1. effective at assessing the
      impact that an ankle sprain has on an athlete's functional and psychosocial
      status, 2. responsive to changes in an athlete's ankle-related health status, and
      3. valid and reliable as tested.

PMID- 12793495
TI  - Chondroblastoma of the talus treated with osteochondral autograft transfer from
      the lateral femoral condyle.
AB  - Chondroblastoma is a benign cartilaginous lesion of bone. When occurring in a
      position juxtaposed to articular cartilage, treatment is directed at removal of
      the tumor with preservation of the articular cartilage. In this case, a
      chondroblastoma of the talus with erosion into the articular cartilage was
      treated with transfer of an osteochondral autograft from the ipsilateral femoral
      condyle. At two-year follow-up, the patient was symptom free and magnetic
      resonance imaging revealed complete incorporation of the graft. This case is
      presented as a representative example of osteochondral autograft transfer surgery
      (OATS) for the treatment of chondroblastoma.

PMID- 12793496
TI  - Unrealistic expectations--dentistry's demon!

PMID- 12793498
TI  - Understanding types may enhance working relationships.

PMID- 12793497
TI  - Clifton Orrin Dummett, Sr.--content of character.

PMID- 12793499
TI  - Scientist finds gene that determines major sensitivity to bitter taste.

PMID- 12793500
TI  - Prosthodontic treatment planning: current practice, principles, and techniques.
AB  - In this series of articles, the faculty of the University of Southern California
      New Odontic Seminar have taken the 25 years of documented treatment of sample
      patient "A.K." and used it as a foundation on which to base discussion of the
      concepts and technology that have developed in prosthodontic treatment planning.
      Each of the contributing authors was asked, "What are your thoughts
      retrospectively if you were to treat the patient A.K. in your practice today?"
      And, since all dentists are challenged with evidence-based treatment planning,
      each author was also asked "On what evidence in the literature do you base your
      treatment planning for patients who need prosthetic therapy?" Dentistry's
      experience with long-term success of endodontics, periodontics, and implant
      dentistry is expressed in the presentations discussing when an implant may be
      better suited for a prosthetic abutment than a restored tooth.

PMID- 12793501
TI  - A.K. patient presentation.

PMID- 12793502
TI  - Perio-prosthetic treatment planning in implant dentistry.

PMID- 12793503
TI  - Treatment planning for the future: endodontics, post and core, and periodontal
      surgery--or an implant?

PMID- 12793504
TI  - Treatment planning considerations: questionable teeth or implants?

PMID- 12793505
TI  - Treatment considerations of fixed prosthetic restorations of the compromised
      dentition vs. alternate fixed implant-supported options.

PMID- 12793506
TI  - Implant-retained removable prosthetic designs for patients with maxillary
      posterior edentulism.

PMID- 12793508
TI  - What can we offer patients with today's advancements in dental materials?

PMID- 12793509
TI  - Anxiety management.

PMID- 12793507
TI  - The evolution of implant therapy for the edentulous patient.

PMID- 12793510
TI  - How to avoid community psychiatry?

PMID- 12793511
TI  - Attitudes towards suicide in Slovenia: a cross-sectional survey.
AB  - BACKGROUND: Slovenia has been experiencing a very high suicide rate (30 per
      10,000 inhabitants per year or higher) and there are no data on public attitudes
      towards suicide in Slovenia. AIMS: To identify public attitudes towards suicide
      in order to expand the basis for prevention. METHODS: A Suicide Attitudes
      Questionnaire (SUIATT) was sent to a representative sample of adult Slovenian
      citizens. RESULTS: Some 5.2% of respondents had at least one previous suicidal
      attempt and 21.6% reported suicidal ideation (SI). More respondents with SI than
      respondents without SI reported: 1) the suicidal act as deliberated, 2) less
      importance attached to the mental illness in suicidal behaviour, 3) that a person
      has the right to commit suicide, and 4) the suicidal act as an act of cowardice.
      CONCLUSIONS: Results do not allow a general statement whether attitudes towards
      suicide are permissive or restrictive. However, in the subgroup of respondents
      with SI we found a tendency towards permissiveness regarding suicide.

PMID- 12793512
TI  - Attitudes of hospital staff toward mentally ill patients in a teaching hospital,
      Turkey.
AB  - The aim of this study was to examine the attitudes of hospital staff toward major
      mental diseases: schizophrenia and depression. Negative attitudes were common
      among all of the hospital staff, and were more common among academicians,
      resident physicians and nurses. Causes of attitude variations were discussed.
      BACKGROUND: Attitudes of hospital staff are important for admission, early
      diagnosis and treatment, and the rehabilitation process of mentally ill patients.
      AIMS: The main objective of this study was to investigate and compare hospital
      workers' attitudes toward and knowledge of schizophrenia and depression. METHODS:
      In 2001, a total of 160 hospital staff (40 academicians, 40 resident physicians,
      40 nurses and 40 hospital employees) in a teaching hospital were interviewed with
      a questionnaire. The questionnaire included items about background information, a
      one-paragraph vignette, questions on social distance and expected burden,
      recognition of mental illness, hospitalization, prognostic outcome, and to whom
      and where the patient should be admitted. RESULTS: Although academicians,
      resident physicians, and nurses have sufficient knowledge about schizophrenia and
      depression, the frequency of their negative attitudes towards mentally ill
      subjects was more than that for uneducated hospital employees. CONCLUSIONS: It
      was commented that this difference might be as a result of negative effects of
      the medical education system.

PMID- 12793513
TI  - Discharges of patients from public psychiatric hospitals in Italy between 1994
      and 2000.
AB  - BACKGROUND: Psychiatric hospitals in Italy had to be closed under a law dated
      1994. AIMS: To investigate the discharge of patients from public psychiatric
      hospitals. METHODS: A total of 4492 patients from 22 psychiatric hospitals were
      described at recruitment and followed during the period 1994-2000. Their
      characteristics were investigated as determinants of discharge to community
      residential facilities for psychiatric patients versus other settings. RESULTS:
      All 22 psychiatric hospitals closed between 1994 and 2000; 678 patients had died,
      and the remainder were discharged. Of these, 39% went to nursing homes, 29% to
      community residential facilities for psychiatric patients, 2% joined their
      family, less than 1% were settled in private independent accommodation, and 29%
      remained in the psychiatric hospital, although defined as discharged. Ten
      patients were recorded as missing when still in the psychiatric hospitals, none
      after discharge. Younger, more educated patients and patients from two of the
      four regions studied were more likely to be discharged to community residential
      facilities. CONCLUSIONS: The majority of patients were discharged to highly
      supervised settings. The potential risk of abandonment due to
      deinstitutionalization was not observed in this population. The wide use of
      highly supervised settings can be explained by the patients' old age, but
      different local policies may have affected the discharge process.

PMID- 12793514
TI  - Puppy pregnancy in humans: a culture-bound disorder in rural West Bengal, India.
AB  - BACKGROUND: Delusion of pregnancy in males, though uncommon, has been reported in
      the literature. Delusion of animal pregnancy in humans is unreported until now,
      and we are reporting here cases of puppy pregnancy in human beings from a part of
      rural West Bengal, India. MATERIAL: Studies of six male cases and one female case
      of delusion of puppy pregnancy after an alleged touch or bite of a dog are
      presented. DISCUSSION: Detailed phenomenological analysis revealed that there
      exists a strong cultural belief that dog bite may evolve into a puppy pregnancy
      even in the human male. Psychiatric status showed that there was a clear
      association of obsessive-compulsive disorder in two cases, anxiety-phobic locus
      in one and three showed no other mental symptom except this solitary false belief
      and preoccupation about the puppy pregnancy. All the cases were from rural areas
      and their communities endorse this pathogenic event of puppy pregnancy in humans.
      One case (11-year-old child) exemplified how the social imposition of this
      cultural belief made him a case that allegedly vomited out an embryo of a dog
      foetus. CONCLUSION: Although the belief in puppy pregnancy is culturally shared,
      the cases presented a mix of somatic and psychological complaints and their help
      seeking behaviour was marked. These features prompted us to identify this
      phenomena as a culture-bound disorder which needs proper cultural understanding
      for its effective management.

PMID- 12793515
TI  - Two levels of intervention in low-income women with depressive symptoms:
      compliance and programme assessment.
AB  - AIMS: This study reports on the evaluation of a brief group intervention for
      women of limited means with depressive symptoms. METHOD: A comparison design was
      used with pre-, post- and four-month follow-up assessments for 93 women in the
      group intervention condition who were given six two-hour sessions of psycho
      educational intervention, and 42 women in a minimum individual condition who
      received a 20-minute explanation in addition to the educational material, which
      yielded the following results. RESULTS: Both conditions were effective in
      motivating participants to engage in self-help activities (making time for
      themselves every week, using writing as a means of sorting out problems, talking
      to someone about their problems and carrying out the reflection and cognitive
      behavioural exercises) and to seek further professional help when necessary. The
      intervention condition was more positively evaluated since participants regarded
      it as having a greater influence on their life and problems. Influence was
      related to better understanding and coping with problems, mood improvement,
      changes in the way they thought about things, knowing themselves better and being
      more accepting of themselves. CONCLUSIONS: The results suggest that both
      interventions tackle important issues related to depression in women but further
      data are needed for a better understanding of this relationship.

PMID- 12793516
TI  - Service variation in baseline variables and prediction of risk in a randomised
      controlled trial of psychological treatment in repeated parasuicide: the POPMACT
      Study.
AB  - The treatment protocol and baseline characteristics of 480 subjects with a
      history of repeated parasuicide recruited in five centres to a randomised
      therapeutic trial of manual assisted cognitive-behaviour therapy (MACT) and
      treatment as usual (TAU) are described. Most patients had significant anxiety and
      depressive disturbance with 42% having a personality disorder. Variation in
      service policies influenced recruitment, with earlier assessment centres seeing
      people with more frequent episodes of self-harm and greater parasuicide risk than
      later ones. Parasuicide risk was also significantly greater in those with their
      first parasuicide episode at an earlier age and in those with a more recent
      latest episode.

PMID- 12793517
TI  - Is there an association between life events, postnatal depression and thyroid
      dysfunction in thyroid antibody positive women?
AB  - BACKGROUND: Postnatal depression is more common in women positive for thyroid
      autoantibodies, independent of thyroid hormone dysfunction, but the basis of this
      association is unclear. AIMS: The objective of the work reported here has been to
      investigate from data obtained from previously published research, a possible
      association between life events, postnatal depression and the development of
      thyroid dysfunction in women who are positive for thyroid autoantibodies. METHOD:
      A cohort of pregnant women whose thyroid antibody status was positive (N = 115),
      was identified at antenatal booking (approximately 16 weeks). These, and a group
      of women negative for thyroid antibodies (N = 123), were assessed for depression
      at six to eight weeks postpartum and then at 12, 20 and 28 weeks postpartum
      according to Research Diagnostic Criteria (RDC). The number and type of life
      events over the preceding year were also assessed at eight weeks postpartum using
      Paykel's Life Event Schedule. At four weekly intervals post-partum until six
      months, thyroid antibody levels and thyroid function (plasma T3 T4 and TSH) were
      measured. RESULTS: As anticipated, the thyroid antibody status remained the same
      throughout the study, and there was no difference in the number or type of life
      events reported in the preceding year, between antibody positive and antibody
      negative women. Postnatal depression was associated with an excess of both total
      and negative life events, independent of thyroid antibody status or actual
      thyroid hormonal status. Women who developed thyroid dysfunction did not report
      an excess of life events (total, negative or neutral) in the preceding year.
      CONCLUSION: There was an excess of reported total and negative life events in
      women with postnatal depression, but this was independent of thyroid antibody
      status or function.

PMID- 12793518
TI  - Nutritional effects on neuron numbers.
AB  - Undernutrition during early life is known to cause deficits and distortions of
      brain structure although it has remained uncertain whether or not this includes a
      diminution of the total numbers of neurons. Estimates of numerical density (e.g.
      number of cells per microscopic field, or number of cells per unit area of
      section, or number of cells per unit volume of tissue) are extremely difficult to
      interpret and do not provide estimates of total numbers of cells. However,
      advances in stereological techniques have made it possible to obtain unbiased
      estimates of total numbers of cells in well defined biological structures. These
      methods have been utilised in studies to determine the effects of varying periods
      of undernutrition during early life on the numbers of neurons in various regions
      of the rat brain. The regions examined so far have included the cerebellum, the
      dentate gyrus, the olfactory bulbs and the cerebral cortex. The only region to
      show, unequivocally, that a period of undernutrition during early life causes a
      deficit in the number of neurons was the dentate gyrus. These findings are
      discussed in the context of other morphological and functional deficits present
      in undernourished animals.

PMID- 12793520
TI  - Inhibitory effect of apelin-12 on nocturnal food intake in the rat.
AB  - Apelin, the endogenous peptide ligand of the APJ receptor, is expressed in brain
      regions implicated in food and water intake. This study reports for the first
      time, the effect of apelin-12, one of the most potent apelin peptides, on
      spontaneous (nocturnal) feeding. Randomised intracerebroventricular injection of
      1, 3 and 10 nmol apelin-12 or saline vehicle, 10 min prior to lights out, led to
      dose-dependent reductions in food intake 2-4 h after injection (n = 7; p < 0.05).
      This suggests that apelin-12 exerts a delayed inhibitory effect on nocturnal
      feeding. Relative to saline, no effect was observed on total 24-h food intake
      post injection. In contrast, day-time administration of 10 nmol apelin-12 to
      satiated rats stimulated feeding (n = 5-11; p < 0.05); lower doses had no effect.
      No changes in water intake were observed after apelin-12. These results suggest
      that apelin is involved in the central control of feeding.

PMID- 12793519
TI  - Blueberry supplementation enhances signaling and prevents behavioral deficits in
      an Alzheimer disease model.
AB  - Previously, we showed that blueberry (BB) supplementation reversed the
      deleterious effects of aging on motor behavior and neuronal signaling in
      senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1
      transgenic mice showed no deficits in Y-maze performance (at 12 months of age)
      with no alterations in amyloid beta burden. It appeared that the protective
      mechanisms are derived from BB-induced enhancement of memory-associated neuronal
      signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral
      sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the
      first time that it may be possible to overcome genetic predispositions to
      Alzheimer disease through diet.

PMID- 12793523
TI  - Effect of ethanol intake during lactation on male and female pups' liver and
      brain metabolism during the suckling-weaning transition period.
AB  - In rats, a high degree of brain development and myelination occurs during the
      first 15 days after birth. Ethanol intake by lactating rats modified 12 day-old
      pups' brain development and metabolism. The aim of the present study was to
      evaluate the effect of maternal ethanol ingestion during lactation on prepubertal
      (24-day-old) pups' brain and liver metabolism. Lactating rats (4 male and 4
      female litters) were divided into 2 groups: control--received control liquid
      diet, and ethanol--received liquid diet containing 4% of ethanol. On postnatal
      day 24, the pups were killed by decapitation. Liver and brain were utilized for
      measuring Adenosine Tri-phosphate-citrate lyase and malic enzymes activities.
      Brain slices were incubated in medium containing glucose to determine glucose
      consumption and oxidation, and lipid synthesis. The ethanol intake decreased male
      and female pups' body, brain and liver weight. Liver Adenosine Tri-phosphate
      citrate lyase activity was decreased only in male pups of the ethanol group. The
      intake of ethanol solution by the dams increased glucose consumption and
      oxidation by the incubated female pups' brain slices and decreased glucose
      oxidation by the male pups' brain slices. It can be concluded that the effects of
      maternal ethanol intake on pups' development and metabolism are gender-related.

PMID- 12793521
TI  - The differential effects of food restriction on 5-HT1A and 5-HT1B receptor
      mediated control of serotonergic transmission in the hippocampus and hypothalamus
      of rats.
AB  - Serotonergic pathways are considered important in the regulation of appetite. We
      have determined, in female rats, the effects of 4 weeks food restriction (FR) on
      serotonin function, using in vivo microdialysis. We recorded basal 5-HT release
      in the hypothalamus and hippocampus, and the sensitivity of the somatodendritic 5
      HT1A autoreceptors in the raphe nuclei, and the nerve terminal 5-HT1B
      autoreceptors which together regulate the synthesis and release of 5-HT in these
      regions. Sensitivity of the somatodendritic 5-HT1A autoreceptors was assessed by
      measuring the reduction in extracellular 5-HT induced by systemic administration
      of the 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)-tetralin (8-OH
      DPAT), while sensitivity of nerve terminal 5-HT1B autoreceptors was measured by
      observing the increase in 5-HT release after systemic injection of the 5-HT1B
      receptor antagonist GR 127935. Basal release of 5-HT was not affected by FR. 8-OH
      DPAT decreased 5-HT release in the hippocampus and hypothalamus in both groups,
      while GR 127935 increased 5-HT release in both areas in the control animals but
      not in the hypothalamus of the FR animals. Since 5-HT1B receptors regulate 5-HT
      release by a negative feedback mechanism, the decrease in sensitivity of 5-HT1B
      receptors in the hypothalamus of FR rats indicates increased serotonergic
      transmission in these rats. The fact that such differential effects on 5-HT
      release appeared only in the hypothalamus, the center of regulation of energy
      balance, suggests a compensatory role in FR by increasing 5-HT secretion, thereby
      reducing feeding behavior.

PMID- 12793522
TI  - Antioxidant effects of selenium in rat brain and the stimulating role of nitric
      oxide.
AB  - OBJECTIVE: To evaluate the antioxidant effect of selenium on Na+, K(+)-ATPase in
      rat brain in the presence of nitric oxide. METHODS: Male Wistar rats (70 g) were
      treated as follows: group 1 received 1 microg of i.p. sodium nitroprus-side per
      kg (SNP), group 2 received 5 microg sodium selenite during 20 days, group 3
      received sodium selenite 5 microg + SNP 1 microg and the control group received
      vehicle 50 microl (0.9% NaCl), same period and route. At the end of treatment,
      animals were sacrificed and their brain dissected into cortex, hemispheres,
      cerebellum and brain stem in order to determine lipid peroxidation (TBARS), Na+,
      K+ ATPase and total ATPase in each section. Blood hemoglobin concentration (Hb)
      and prostate weight were also assessed. RESULTS: A significant increase of Hb in
      blood and of proteins in cortex and hemisphere was detected, but TBARS values
      fell due to the effect of sodium selenite in all examined regions, except for
      cerebellum. ATPase activity declined in all groups and regions with and without
      NTP. We conclude that diet supplementary selenium to inhibit NO generation can be
      a useful treatment in chronic inflammatory diseases.

PMID- 12793524
TI  - Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level
      in patients with multiple sclerosis.
AB  - Free radical-mediated peroxidation of biological molecules, especially of lipids,
      is implicated in the pathogenesis of a number of diseases like multiple
      sclerosis. Low concentration of antioxidant vitamins: beta carotene, retinol,
      alpha tocopherol and ascorbic acid have been observed in serum or cerebrospinal
      fluid of multiple sclerosis patients. On the basis of these observations, we
      studied the potential lipoprotein oxidation and total antioxidant capacity in the
      pathogenesis of multiple sclerosis. Lipoprotein oxidizability for plasma in
      vitro, serum levels of autoantibodies against oxidized low-density lipoproteins,
      plasma total homocysteine levels with vitamin B12 and folate, and plasma total
      antioxidant capacity were measured in twenty four patients with multiple
      sclerosis and twenty four healthy sex- and age-matched person as control. In
      multiple sclerosis patients during an attack, a significant increase in both in
      vitro lipid oxidizability for plasma and in the levels of autoantibodies against
      oxidized low-density lipoproteins, and a strong decrease in plasma total
      antioxidant capacity were detected. Plasma total homocysteine levels were
      significantly higher in multiple sclerosis patients whose plasma vitamin B12 and
      folate levels were lower but not statistically significant, than controls. The
      present study indicates that lipoprotein oxidation may be important factor in the
      course of multiple sclerosis and in vitro measurements of plasma oxidation
      kinetics as an indication for lipoprotein oxidation might be useful as an
      additional tool for the clinical diagnosis of multiple sclerosis.

PMID- 12793525
TI  - Does short-term diet restriction in mice precipitate the development of anorexia?
AB  - Anorexia nervosa (AN) inevitably begins with dieting. Yet, it is unknown whether
      anyone who will ultimately suffer from anorexia is already ill upon "going on a
      diet", or whether disease begins during, and is perhaps triggered by, dieting.
      The objective of the following study was to precipitate anorexia by imposing diet
      restriction on animals, as a model for generating AN in humans. Three hundred
      young female Sabra mice were diet restricted to 40% of daily nutrient
      requirements for 12 days, lost 17% of body weight and were then re-fed ad-lib.
      All mice regained appetite and weight. Our conclusions are that diet restriction
      does not precipitate anorexia in mice. Our findings do not support a role for
      diet restriction per se in triggering AN.

PMID- 12793526
TI  - Handling of clinical tissue specimens for molecular profiling studies.
AB  - The relationship between gene expression profiles and cellular phenotypes is an
      important aspect of functional genomics. Clinical tissue specimens will play a
      vital role in this effort. The usefulness of tissue for molecular profiling is
      significantly influenced by the manner of specimen handling. Crucial components
      of this process include the optimization of the methods of tissue fixation and
      embedding, not only to obtain excellent histological detail, but also to promote
      the elucidation of the gene and protein expression profiles. In this article, we
      describe handling of clinical specimens using whole-mount prostate as an example,
      the use of new high-throughput techniques that allow molecular profiling analysis
      and the use of a web-based 3-dimensional model to combine these data to make it
      available to clinicians and the research community. Complete protocols and
      additional discussion are available on the website, http://cgap-mf.nih.gov.

PMID- 12793527
TI  - Genomes and evolution.
AB  - Genomics today involves the study of many genes at a time in order to gain an
      integrated picture of the cell or organism as a whole. This review considers the
      architecture and evolution of bacterial genomes. The many facets of large-scale
      functional investigation in a variety of bacteria and the search to find common
      rules in their dynamic and structural organization are discussed. Such rules
      could aid the understanding of common properties and essential differences
      corresponding to elusive functions, or of still unknown bacterial biotopes.

PMID- 12793528
TI  - Detection of single nucleotide polymorphisms.
AB  - Single nucleotide polymorphism (SNP) detection technologies are used to scan for
      new polymorphisms and to determine the allele(s) of a known polymorphism in
      target sequences. SNP detection technologies have evolved from labor intensive,
      time consuming, and expensive processes to some of the most highly automated,
      efficient, and relatively inexpensive methods. Driven by the Human Genome
      Project, these technologies are now maturing and robust strategies are found in
      both SNP discovery and genotyping areas. The nearly completed human genome
      sequence provides the reference against which all other sequencing data can be
      compared. Global SNP discovery is therefore only limited by the amount of funding
      available for the activity. Local, target, SNP discovery relies mostly on direct
      DNA sequencing or on denaturing high performance liquid chromatography (dHPLC).
      The number of SNP genotyping methods has exploded in recent years and many robust
      methods are currently available. The demand for SNP genotyping is great, however,
      and no one method is able to meet the needs of all studies using SNPs. Despite
      the considerable gains over the last decade, new approaches must be developed to
      lower the cost and increase the speed of SNP detection.

PMID- 12793529
TI  - Clockwise and counterclockwise rotating shifts: effects on sleep duration,
      timing, and quality.
AB  - INTRODUCTION: Many air traffic control specialists (ATCS) work relatively unique
      counterclockwise, rapidly rotating shift schedules. Researchers recommend,
      however, that if rotating schedules are to be used, they should rotate in a
      clockwise (CW), rather than a counterclockwise (CCW) direction. Unfortunately,
      few studies have examined CW and CCW rapidly rotating shifts. This study was
      designed to partially remedy this lack by examining the effects of both types of
      schedules on sleep duration, timing, and quality. METHODS: Participants (n = 28)
      worked a week of day shifts (0800-1600 h) followed by two weeks of either a CW (n
      = 14) or CCW (n = 14) shiftwork schedule, including early morning (0600-1400 h),
      afternoon (1400-2200 h), and midnight shifts (2200-0600 h). Participants recorded
      sleep data and subjective ratings of sleep quality, sleepiness, and mood in daily
      logbooks and wore wrist activity sensors to provide an objective source of
      sleep/wake data. RESULTS: There was no effect of rotation condition for any of
      the sleep measures. A main effect for Sleep Period (F (5,16) = 40.9, p < 0.05)
      indicated that both groups received less sleep prior to the early morning shifts
      than before the afternoon and midnight shifts. Sleepiness ratings were highest at
      the end of the midnight shift. DISCUSSION: Rotation condition did not play a
      significant role in the results of any of the sleep or subjective measures. The
      results of this study indicate that two problem areas in both CW and CCW rapidly
      rotating shift schedules are early morning and midnight shifts.

PMID- 12793530
TI  - Clockwise and counterclockwise rotating shifts: effects on vigilance and
      performance.
AB  - INTRODUCTION: Arguments against counterclockwise shift schedules, such as those
      used in air traffic control, are prevalent in the literature; however, few
      studies have examined direction of rotation in rapidly rotating schedules. The
      present study directly compared clockwise (CW) and counterclockwise (CCW) rapidly
      rotating shiftwork schedules on measures of complex and vigilance task
      performance. METHODS: Participants (n = 28) worked day shifts for the first week
      of the study (0800-1600 h), followed by 2 wk of either a CW (n = 14) or CCW (n =
      14) shiftwork schedule. Participants completed three 1.5-h sessions on the
      Multiple Task Performance Battery (MTPB) on each shift. Each session contained
      active- and passive-task components. In addition, participants completed a 0.5-h
      Bakan Vigilance Test at the beginning and end of each shift. RESULTS: A three
      way, rotation condition by shift by session interaction (F (8,19) = 3.0, p <
      0.05) for the active task composite scores and a rotation condition by shift
      interaction (F (4,23) = 6.2, p < 0.05) for the Bakan Vigilance Task indicated
      that effects of rotation condition were modulated by shift type, such that on
      particular shifts, performance in the CCW rotation was actually better than in
      the CW rotation. DISCUSSION: These data do not support the hypothesis that a CW
      rotation will result in better outcomes on complex or vigilance task performance.
      The results of this study indicate that two problem areas in both CW and CCW
      rapidly rotating shift schedules are early morning and midnight shifts.

PMID- 12793532
TI  - Eye movement, vection, and motion sickness with foveal and peripheral vision.
AB  - BACKGROUND: Both motion sickness and the illusion of self-motion (i.e., vection)
      can be induced by moving visual scenes. The results of a previous study imply
      that motion sickness is primarily dependent on visual motion in foveal vision
      while vection is primarily dependent on motion in peripheral vision. HYPOTHESIS:
      It was hypothesized that similar motion sickness would be produced when tracking
      a single moving dot and a full screen of moving dots, but that vection would be
      greater when tracking multiple moving dots. METHOD: Sixteen subjects viewed
      moving images presented on a virtual reality head-mounted display. In one
      condition a single dot moved from left to right at 27 degrees x s(-1) over a
      distance of 18 degrees before returning instantly to its starting point. This
      motion was repeated continuously. In a second condition, five horizontal rows of
      dots, each 18 degrees apart, moved continuously across the screen at 27 degrees x
      s(-1); subjects were instructed to track each dot in the central row as it
      passed. RESULTS: In both conditions, there were nystagmic eye movements with an
      approximate amplitude of 18 degrees at 27 degrees x s(-1). Vection differed
      significantly between the two conditions, with more vection in the condition with
      five rows of dots. Subjects experienced motion sickness symptoms with both the
      single moving dot and the five rows of dots, with no significant difference in
      sickness between the two conditions. Subject ratings of motion sickness and
      vection were not correlated with each other in either of the two conditions.
      CONCLUSIONS: Motion sickness and vection can vary independently. Vection appears
      to be influenced by peripheral vision, as there was an increase in vection with
      full-field stimulation. Motion sickness induced by moving visual scenes may be
      influenced by foveal visual stimulation or by eye movements, as these were the
      same in both conditions.

PMID- 12793531
TI  - Shuttle mission effects on glutamate receptor expression in the developing rodent
      spinal cord.
AB  - BACKGROUND: Within the mammalian central nervous system (CNS), glutamate
      receptors play a fundamental role in excitatory neurotransmission and synaptic
      plasticity. Studies of the neonatal cerebral cortex suggests that rearing
      environment can influence the dynamic patterns of glutamate receptor subunit
      expression during development. We examined this issue in the developing spinal
      cord, a well studied region of the CNS in which activity-dependent synaptic
      plasticity is known to occur. METHODS: We compared the abundance (by immunoblot
      analysis) and tissue distribution (by immunohistology) of glutamate receptor
      subunits in neonatal animals who participated in the Neurolab Space Shuttle
      mission. Flight animals were either postnatal day 8 or 13 at launch and spent the
      next 16 d in microgravity; tissues were recovered within 12 h of landing.
      Littermate control animals were reared on Earth at 1 G. RESULT: Using semi
      quantitative immunoblot assays, no statistically significant differences were
      found in the overall abundance of any glutamate receptor subunit in the spinal
      cords of the two groups of animals. Similarly, immunohistological examination of
      spinal cords revealed no evidence for differences in the distribution of
      glutamate receptor subunits between the two groups of animals. CONCLUSIONS: These
      results indicate that the developmental regulation of glutamate receptor subunit
      expression in the spinal cord is not appreciably affected by the conditions
      associated with this space shuttle mission and prolonged rearing period in
      microgravity.

PMID- 12793533
TI  - Muscle activity in pilots with and without pressure breathing during
      acceleration.
AB  - BACKGROUND: Fighter pilots are frequently exposed to high acceleration (+Gz)
      forces during sorties. To counter these forces the pilots wear anti-G ensembles,
      use positive pressure breathing for G protection (PBG), and perform anti-G
      straining maneuvers (AGSMs). The purpose of this study was to analyze the muscle
      activity during sustained high G when no positive pressure breathing was used
      (control) compared with that during the use of PBG. METHOD: Seven Swedish Air
      Force fighter pilots volunteered to be exposed to gradual and rapid onset runs to
      +9 Gz with and without PBG in a human centrifuge. Surface electromyography was
      recorded from the intercostals, rectus abdominis, vastus lateralis, biceps
      femoris, and gastrocnemius lateralis. Measured variables included mean muscle
      activity, relative time with high muscle activity levels, and individual
      activation preferences. RESULTS: G duration tolerance was significantly longer (p
      = 0.028) when PBG was used (57 s) compared with control (32 s) during rapid onset
      runs. The vastus lateralis and the gastrocnemius lateralis generated activity >
      50% of a reference contraction for a longer relative time during control (5.8%
      and 33.6%, respectively) than during PBG (0.3% and 12.7%, respectively).
      Cumulative muscle activity during acceleration was compared between trials and
      indicated that some pilots preferred contracting their leg muscles and others
      their abdominal muscles. CONCLUSION: G duration tolerance time increased when PBG
      was used during rapid onset sustained exposures. Less relative time with high
      muscle activity was seen during the use of PBG in two groups of leg muscles. The
      pilots seemed to have individual muscle activation sequence preferences while
      performing the AGSMs.

PMID- 12793534
TI  - Production of isometric forces during sustained acceleration.
AB  - BACKGROUND: The operation of high-performance aircraft requires pilots to apply
      finely graded forces on controls. Since they are often exposed to high levels of
      acceleration in flight, we investigated to what extent this ability is degraded
      in such an environment. METHODS: Twelve healthy non-pilot volunteers were seated
      in the gondola of a centrifuge and their performance was tested at normal gravity
      (1 G) and while exposed to sustained forces of 1.5 G and 3 G oriented from head
      to foot (+Gz). Using an isometric joystick, they attempted to produce force
      vectors with specific lengths and directions commanded in random order by a
      visual display. RESULTS: Acceleration had substantial effects on the magnitude of
      produced force. Compared with 1 G, maximum produced force was about 2 N higher at
      1.5 G and about 10 N higher at 3 G. The size of this effect was constant across
      the different magnitudes, but varied with the direction of the prescribed force.
      CONCLUSIONS: Acceleration degrades control of force production. This finding may
      indicate that the motor system misinterprets the unusual gravitoinertial
      environment and/or that proprioceptive feedback is degraded due to increased
      muscle tone. The production of excessive isometric force could affect the safe
      operation of high-performance aircraft.

PMID- 12793535
TI  - Model of CNS O2 toxicity in complex dives with varied metabolic rates and
      inspired CO2 levels.
AB  - INTRODUCTION: Clinical hyperbaric oxygen (HBO) therapy and the use of pure oxygen
      or gases having a high partial pressure of oxygen in diving carry a risk of
      central nervous system (CNS) oxygen toxicity. Previously, we solved the power
      equation K = t2(PO2/101.3)C for humans, where t is the exposure time, PO2 is the
      oxygen pressure, and K is the cumulative oxygen toxicity index. The value of c
      was 6.76, and a symptom may appear when K reaches a threshold value Kc = 2.31 X
      10(8) (Arieli et al. J Appl Physiol 2002; 92:248-56). METHODS AND RESULTS: The
      calculation of K for a complex exposure profile made it possible to estimate risk
      from the normal distribution for a metabolic rate of 1.28 L x min(-1), Z =
      [ln(K0.5)-9.63]/2.02 and for 0.9 L x min(-1), Z = [ln(K0.5)-11.19]/1.35. The
      predicted risk was in agreement with the reported risk in composite exposures.
      The parameters c and ln(Kc) in the power equation are linearly related to
      metabolic rate (M) and inspired CO2 in rats. Due to the assumed similar
      relationship between the data from rats and humans, the mean time to CNS oxygen
      toxicity (tc(M)) as a function of metabolic rate may be calculated for humans as
      follows: tc(M) = [(e(-2.85 M + 31.8))/(PO2/101.3)(-7.45 M + 39.6)]0.5, where M is
      metabolic rate in units of resting metabolic rate. A parallel equation for the
      mean time to toxicity as a function of PCO2 was derived for the rat. This
      equation can be transformed to express the latency in humans, once the parameters
      for humans are known. CONCLUSIONS: The power equation that predicts oxygen
      toxicity in humans was extended to include a complex diving profile as well as
      the effects of metabolic rate and CO2.

PMID- 12793536
TI  - Autonomic mechanisms of bradycardia during nitrox exposure at 3 atmospheres
      absolute in humans.
AB  - BACKGROUND: This experiment was designed to examine the involvement of the
      autonomic nervous systems and intrinsic component in the occurrence of hyperbaric
      bradycardia. METHODS: Eight male divers were exposed to a N2-O2 (Nitrox)
      environment at 3 atmospheres absolute (ATA) for 7 d. The heart rate (HR), plasma
      norepinephrine (NE), and a spectral power of the variability of cardiac interval
      were measured during a 4-d predive control period, a 7-d saturation period at 3
      ATA, and a 4-d postdive period. In each dive period, atropine and propranolol
      were administered intravenously for cholinergic blockade and beta-adrenergic
      blockade, respectively. RESULTS: Basal HR decreased by -10% (p < 0.05) during the
      saturation period compared with that of the predive control. The HR after an
      administration of atropine was attenuated by 5.5 +/- 2.4% (p < 0.05) during
      hyperbaric exposure. The HR after a simultaneous administration of atropine and
      propranolol, the intrinsic HR, was similar throughout the dive periods. Plasma NE
      decreased at 3 ATA (p < 0.05). The basal level of high-frequency power of cardiac
      interval variability, an index of cardiac parasympathetic modulation, remained
      unchanged throughout the dive period, whereas this power was eliminated by
      atropine administration. CONCLUSIONS: These results suggest that reduced
      sympathetic activity plays a primary role in the reduction of HR in the present
      hyperbaric environment.

PMID- 12793537
TI  - Behavioral contagion in an experimental motion environment.
AB  - BACKGROUND: It is generally understood that whole-body movement up and down can
      produce motion sickness. A standard reference, published in this journal in 1974,
      found that a frequency of 6 cycles per minute was most productive of motion
      sickness. The 1974 study used a vertical oscillator carrying two subjects at a
      time. The investigators were, of course, aware that the sight, sound, or smell of
      another person being ill might itself contribute to sickness. Accordingly, the
      two subjects were located in completely separate compartments, each soundproofed
      and with its own independent air-conditioning system. The sessions were scheduled
      to last 2 h. However, if a subject "pre-terminated" (became ill or requested
      removal), the oscillator was stopped while the subject debarked. METHODS: The
      present study is a secondary analysis of data elements not reported in the
      original study, namely, the frequency of pairs in which 0, 1, or 2 subjects pre
      terminated. If knowing that the other subject had pre-terminated had no effect on
      whether the remaining subject pre-terminated, then the pairs in which 0, 1, or 2
      subjects pre-terminated should be distributed binomially. RESULTS: Independent
      pre-termination of the two subjects in a pair was rejected (p < 0.001). The
      likelihood that a subject would pre-terminate increased strongly when the
      subject's partner pre-terminated. This effect was twice as large when the motions
      of the oscillator were severe as when they were less severe. CONCLUSIONS: Pre
      termination by one subject legitimized pre-termination by example, and thereby
      increased the risk that the remaining subject would also pre-terminate
      (behavioral contagion).

PMID- 12793538
TI  - Antioxidative enzyme profiles in fighter pilots.
AB  - INTRODUCTION: Levels of serum lipids and antioxidative agents are known to be
      important in people at risk for heart disease, but less is known about these
      factors in clinically healthy populations such as pilots. METHODS: We measured
      the activities of red blood cell antioxidative enzymes, total antioxidative
      activity in serum (TAS), and lipid concentrations in 229 fighter pilots in the
      Polish Air Force. Measured variables included total cholesterol (T-CH), as well
      as its low-density and high-density lipid components (LDL-CH and HDL-CH,
      respectively). We then calculated the atherogenicity index (T-CH/HDL-CH). In
      addition, we measured the activities of superoxide dismutase (SOD), glutathione
      peroxidase (GPx), and TAS. RESULTS: The mean lipid concentrations in the group
      studied fell in the expected normal ranges. However, only 22.2% of pilots had
      normal or below-normal lipid levels, while the majority displayed some level of
      hyperlipidemia (40.6% mild, 30.4% moderate, 7.4% severe). The mean atherogenic
      index was > 5. The mean activities of SOD, GPx, and TAS exceeded the upper limits
      of normal. Individuals with T-CH > 7.7 mmol x L(-1) had low activities of SOD,
      GPx, and TAS. Presence of normal T-CH concentration did not exclude an abnormal
      atherogenicity index. CONCLUSIONS: Normal T-CH concentration in a healthy
      population does not exclude a concomitant increase in LDL-CH and/or reduction in
      HDL-CH and an abnormal atherogenicity index. Those who provide medical support to
      pilots should emphasize the importance of a proper diet, physical activity, and
      use of hypolipemic drugs when indicated.

PMID- 12793539
TI  - Modafinil--medical considerations for use in sustained operations.
AB  - An understanding of the consequences of sustained operations involving prolonged
      sleep deprivation is important to the military. Losses in cognitive performance
      of the order of 30% after one night and 60% after two nights of sleep loss have
      been shown to occur in several studies. Napping strategies have been proposed as
      one coping strategy for these performance decrements. An alternate solution is
      the use of stimulants. Modafinil may offer a safer alternative to more commonly
      used psychostimulants. It has been shown to counteract the effects of sleep
      deprivation with fewer side effects than amphetamine. Recent studies on the
      effects of modafinil during sleep deprivation are reviewed and compared with
      those of other stimulants such as amphetamine and caffeine, and to prophylactic
      naps. Recommendations are proposed for the use of modafinil in sustained military
      missions. For missions of about 24 h, modafinil is preferable to naps. For longer
      missions, naps should be considered, along with the concomitant use of modafinil
      to help maintain performance levels. The authors discuss apparent
      'overconfidence' and hyperthermia-inducing effects of modafinil, and advise that
      these effects be taken into account if modafinil is to be used in any mission
      conducted in the field or in hot environments. It is also recommended that
      individual sensitivity to the drug should be tested before any mission of a
      sustained nature, especially if it involves small operational groups or combat
      aircrew, where the impact of such effects on individuals would be more critical.

PMID- 12793540
TI  - Proteinuria in aviation personnel: waiver policy in the U.S. Navy.
AB  - BACKGROUND: Proteinuria is a condition occasionally detected both in applicants
      for military pilot training and in experienced pilots. Medical personnel involved
      in the care of either group require a standardized policy for the evaluation and
      aeromedical disposition of proteinuria for these personnel. METHODS: A literature
      search was conducted to obtain current information and prognostic data on
      proteinuria in the general medical literature. Generally accepted waiver
      principles were then examined to determine if proteinuria should be waivered in
      aviation personnel. Other agency policies regarding proteinuria in aviation
      personnel were examined. The biomedical database records at the Naval Aerospace
      Medical Institute (NAMI) were searched to discover the U.S. Navy's experience in
      the evaluation and disposition of aviation personnel with proteinuria. RESULTS: A
      review of the general medical literature revealed general categories of
      proteinuria (dependent on protein excretion amount and symptomatology) and the
      presence or absence of systemic disease that correlated well with prognostic
      data. These categories provided useful criteria to develop an aeromedical policy
      that was consistent with previous (informal) NAMI policies, generally accepted
      waiver principles, and the existing policies of other agencies. Using the above
      results, a recommended policy for aviation personnel with proteinuria was
      presented. CONCLUSIONS: A recommended policy for the evaluation and aeromedical
      disposition of aviation personnel with proteinuria was developed for both
      applicants for U.S. Navy aviation duty as well as in those already serving within
      the U.S. Navy aviation community.

PMID- 12793541
TI  - Acceleration effects on pupil size with control of mental and environmental
      factors.
AB  - BACKGROUND: Using still photography and cinematography, early studies reported
      that pupils dilate immediately on exposure to acceleration and the dilation
      persists during sustained +Gz. Due to the lack of control for mental and
      environmental factors and poor sampling rate in early techniques, we re-examined
      the effects of increased acceleration on pupil size in the human centrifuge.
      METHODS: Eight volunteers were dark adapted for 20 min by fixating on a 2.5 mm
      LED disk, 1 m away in otherwise complete darkness. Pupil diameters and horizontal
      and vertical eye movements were recorded binocularly in real time using an eye
      tracking and pupillometry system. The recording sequence consisted of 1 min at +1
      Gz, followed by transition to +3 Gz at 0.1 G x s(-1) 2 min at sustained +3 Gz,
      return to +1 Gz at 1 G x s(-1), and finally maintained at +1 Gz for another
      minute. During this sequence, the subject's heart rate was also monitored and the
      subject was instructed to subtract 2 from 1000 to maintain mental alertness.
      RESULTS: All subjects showed a significant decrease in pupil diameter (p < 0.05)
      and increase in heart rate (p = 0.02) during +3 Gz and regained the baseline
      level on sustained acceleration ranged from 0.6 to 3.3 mm. CONCLUSION: Our
      findings suggest that pupils constrict during hypergravity. It appears that the
      reflex regulation of pupil size is attributed to parasympathetic action through
      fibers originating in Edinger-Westphal's nucleus in the mesencephalon, which
      receives direct input from the otoliths.

PMID- 12793542
TI  - Case history of serious altitude decompression sickness following rapid rate of
      ascent.
AB  - Neurologic and respiratory decompression sickness (DCS) symptoms occurring in the
      same individual represent complications rarely observed in altitude research. A
      case is presented of multi-symptom serious DCS resulting from exposure to 12,192
      m (40,000 ft). Following 90 min of preoxygenation, the patient was decompressed
      in a hypobaric chamber from ground level to 12,192 m in 30 s. After 69 min at
      altitude he developed substernal chest pressure and the flight was immediately
      terminated. During the chamber descent the patient appeared disoriented. By 5486
      m (18,000 ft) his chest pressure had resolved. The post-flight medical exam
      revealed multiple neurological abnormalities. He underwent a Table VI hyperbaric
      oxygen treatment with complete resolution of all abnormal neurological findings.

PMID- 12793543
TI  - Electronic pilot-activity monitor: a countermeasure against fatigue on long-haul
      flights.
AB  - BACKGROUND: Previous studies have shown frequent reductions in aircrew alertness
      during long-haul flights, even during the critical descent phase. Recommended
      countermeasures include alternation of crew activity with rest, such as cockpit
      napping. However, a method of monitoring the alertness level of the active and
      napping pilots should be considered. METHODS: The Electronic Pilot-Activity
      Monitor (EPAM) continuously monitors the activity of the crew (activity mode) and
      limits nap duration (timer mode) to prevent sleep inertia effects. The EPAM is
      currently being validated during actual long-haul flights. To date, we have
      studied 14 round trips Brussels-New York-Brussels (i.e., 28 flights).
      Physiological parameters, including electroencephalogram, electrooculogram, and
      heart rate, were recorded continuously to evaluate the ability of EPAM to detect
      low alertness phases. RESULTS: We present preliminary results showing that the
      EPAM can detect some microsleep periods during the flight. However, some
      microsleeps occurred while the pilot was active. In the timer mode, the EPAM was
      able to limit sleep duration but some deep sleep was observed. DISCUSSION: These
      results suggest that additional measures (e.g., eye closure duration) should be
      included to improve the detection of drowsy periods. In addition, the timer mode
      should be improved to prevent deep sleep in order to prevent subsequent sleep
      inertia.

PMID- 12793544
TI  - Case from the aerospace medicine residents' teaching file. Chorioretinitis due to
      toxoplasmosis.
AB  - An aviator presented with visual changes which proved to be chorioretinitis due
      to toxoplasmosis. The evaluation, treatment, and aeromedical disposition of this
      pilot are discussed.

PMID- 12793545
TI  - Navy flight line medicine and the medical treatment facility: the optimal
      relationship.

PMID- 12793546
TI  - This month in aerospace medicine history-June 2003.

PMID- 12793547
TI  - Dupuytren's disease.

PMID- 12793548
TI  - Surgical priorities in damage control in polytrauma.

PMID- 12793549
TI  - A strategy for reducing blood-transfusion requirements in elective orthopaedic
      surgery. Audit of an algorithm for arthroplasty of the lower limb.
AB  - We prospectively audited 79 patients undergoing primary knee or hip arthroplasty
      (38 knees, 41 hips) and found that 66% (58% of knees, 73% of hips) had at least
      one unit of blood transfused postoperatively, with a mean transfusion requirement
      of 13 units per patient (1.1 for knees, 0 to 6; 1.5 for hips, 0 to 4). We then
      established a new protocol for postoperative blood transfusion. This requires the
      calculation of the maximum allowable blood loss (MABL) that each individual
      patient can safely lose based upon their weight and preoperative haematocrit. The
      total blood loss up to this volume is replaced with colloid. When a patient's
      total blood loss reaches their MABL their haematocrit is measured at the bedside
      using the Microspin system (Bayer plc, Newbury, UK). If their haematocrit is low
      (< 0.30 for men, < 0.27 for women), blood is transfused. As a safety net all
      patients have their haemoglobin formally checked on days 1, 2, and 3 after
      surgery and have a transfusion if the haemoglobin levels are less than 8.5 g/dl.
      We conducted a further audit of 82 patients (35 knees, 47 hips) after the
      introduction of this protocol. Under the new protocol only 24% of patients
      required blood (11% of knees, 34% of hips) with a mean transfusion requirement of
      0.56 units per patient (0.26 for knees, 0 to 4; 0.79 for hips, 0 to 4). The use
      of clinical audit and the introduction of strict guidelines for transfusion can
      change transfusion practice and result in improved patient care. Our transfusion
      protocol is a simple and effective method of keeping transfusion to a minimum and
      is particularly useful in departments which do not have the facility to use
      autologous blood or reinfusion drains for relective orthopaedic surgery.

PMID- 12793550
TI  - Body-exhaust suit versus occlusive clothing. A randomised, prospective trial
      using air and wound bacterial counts.
AB  - We randomly allocated 50 total knee replacements to scrub teams wearing body
      exhaust suits (BES) or Rotecno occlusive clothing. The effectiveness of the
      clothing was assessed using air andwound bacterial counts. Bacteria were
      recovered from 62% of wounds (64% BES, 60% Rotecno). The mean air count was 0.5
      CFU/ m3 with BES and 1.0 CFU/m3 with Rotecno (p = 0.014). The mean wound counts
      were 14 bacteria/wound with BES and eight bacteria/wound with Rotecno (p =
      0.171). There was no correlation between the air and wound counts (r = -0.011,
      Spearman's). The higher air counts suggest that Rotecno occlusive clothing is
      less effective than BES, but wounds were equally contaminated with both types of
      clothing suggesting that at very low levels of air contamination the contribution
      of bacteria to the wound from the air is irrelevant. Even doubling the air counts
      from 0.5 to 1.0 CFU/m3 had no detectable effect on the wound. This allows a
      reassessment to be made of other sources of contamination the effect of which
      would previously have been overwhelmed by contamination from air.

PMID- 12793551
TI  - Patient versus surgeon satisfaction after total hip arthroplasty.
AB  - We compared patient satisfaction with surgeon satisfaction after total hip
      arthroplasty (THA) in a group of 193 patients (200 THAs, mean follow-up six
      years) using a visual analogue scale (VAS), and two objective and two subjective
      scoring systems. We also determined the survival rate with different endpoints.
      For the 121 hips available for clinical follow-up, we did not find a significant
      difference in satisfaction between patient and surgeon. In a subgroup with low
      patient satisfaction, the surgeon was more satisfied than the patient (p = 0.04).
      The correlation between the patient satisfaction VAS and the different subjective
      and objective scoring systems suggests that pain during activity is the most
      important factor for the patient. The survivorship at six years decreased from
      96.6% to 83.7% if dissatisfaction (VAS > 20) was added to revision as an endpoint
      in the survival analysis. The patient satisfaction VAS provides additional
      information to evaluate the outcome of THA. We recommend the use of both
      subjective and objective scoring systems to evaluate the outcome of THA.

PMID- 12793552
TI  - Degradation of hydroxyapatite coating on a well-functioning femoral component.
AB  - We carried out a histological study of a proximally hydroxyapatite (HA)-coated
      femoral component, retrieved after 9.5 years of good function. The HA coating had
      completely degraded. Bone was in direct contact with the titanium surface in all
      the areas which had been coated, with no interposing fibrous tissue. There were
      no signs of particles, third-body wear, adverse tissue reactions or osteolysis.
      Bone remodelling was evident by the presence of resorption lacunae; tetracycline
      labelling showed bone laid down six years after implantation. The loss of the HA
      coating had no negative effect on the osseo-integration of the stem. We conclude
      that the HA coating contributes to the fixation of the implant and that its
      degradation does not adversely affect the long-term fixation.

PMID- 12793553
TI  - Zirconia and alumina ceramics in comparison with stainless-steel heads.
      Polyethylene wear after a minimum ten-year follow-up.
AB  - Although alumina has been used in orthopaedic surgery since the 1970s, the long
      term clinical results of zirconia have not been well documented in vivo. We
      studied hips with these two different ceramics during the same period and with a
      minimum follow-up of ten years. Because the size of the alumina and zirconia
      heads was different, hips with 32 mm alumina heads and those with 28 mm zirconia
      heads were compared with control hips with stainless-steel heads of the same
      size. Our aim was to compare the two ceramics. There was an increased linear rate
      of penetration of the femoral heads into the liner between years five and 12 for
      the zirconia and the stainless-steel groups. This was severe in the zirconia
      group (0.4 mm/year compared with 0.13 mm/year for the stainless-steel group).
      During the same 12-year period there was, however, no significant change in the
      rate of wear in the alumina group (0.07 mm/year). The mean wear at the most
      recent follow-up was 1360 mm3 for the 28 mm zirconia group, 683 mm3 for the 28 mm
      stainless-steel group, 755 mm3 for the 32 mm alumina group and 1314 mm3 for the
      32 mm stainless-steel group. The monoclinic content rose on the surface of three
      zirconia heads which were retrieved at revision. This change was associated with
      an increase in the surface roughness. A change in the roundness with an increase
      in the sphericity deviation was also observed both in the articular and non
      articular parts of the femoral heads. The increase in rate of wear in the
      zirconia group was only evident after eight years and may be linked to a long
      term biodegradation of zirconia in vivo, associated with the altered roughness
      and roundness which was observed on the retrieved heads.

PMID- 12793554
TI  - Trochanteric slide osteotomy in revision total hip arthroplasty for loosening.
AB  - We used a trochanteric slide osteotomy (TSO) in 94 consecutive revision total hip
      arthroplasties (90 with replacement of both the cup and stem). This technique
      proved to be adequate for removing the components, with few complications (two
      minor fractures), and for implanting acetabular allografts (18%) and
      reinforcement devices (23%). Trochanteric union was obtained in most patients
      (96%), even in those with septic loosening (18/19), major femoral osteolysis
      (32/32), or previous trochanteric osteotomy (17/18). TSO is versatile, since it
      can be extended by a femoral flap (four cases) or a distal femoral window (eight
      cases). Despite significant bone loss, in 24% of the femora and 57% of the
      acetabula, favourable midterm results were achieved and only six reoperations
      were required, Including two for trochanteric nonunion and two for loosening. It
      leaves the lateral femoral cortex intact so that a stem longer than 200 mm was
      needed in only 25% of patients. This is a considerable advantage compared with
      the extended trochanteric osteotomy in which the long lateral flap (12 to 14 cm)
      requires an average length of stem of 220 mm beyond the calcar. TSO provides an
      approach similar in size to the standard trochanteric osteotomy but with a rate
      of nonunion of 4% versus 15%. It reduces the risk of difficulties with removal of
      the stem, and removes the need for routine distal anchoring of long revision
      stems. The limited distal femoral compromise is very important in patients with a
      long life expectancy.

PMID- 12793555
TI  - The results of revision knee arthroplasty with and without retention of secure
      cemented femoral components.
AB  - We have compared the survival of 67 revision arthroplasties of the knee
      undertaken for aseptic loosening with and without the retention of a secure,
      cemented femoral component. All the patients had undergone a single primary
      procedure at a mean of nine years previously. In group I (25 knees) the original
      femoral component was secure and was retained. There were no abrasions or
      osteolysis. The knees were stable, normally aligned, with minimal bone loss. In
      group 1142 knees did not fulfil these criteria and underwent revision of both
      components. The mean follow-up was four years. Re-revision for loosening was
      required in seven knees (28%) in group I and three (7%) in group II (p < 0.01).
      The remaining knees function well with Knee Society scores averaging 84/69 and no
      radiological evidence of osteolysis. When revising cemented implants, retention
      of a secure femoral component cannot be recommended even when conditions appear
      to be suitable.

PMID- 12793556
TI  - Outcome after reconstruction of the anterior cruciate ligament in athletic
      patients. A comparison of early versus delayed surgery.
AB  - We randomised 31 patients with acute tears of the anterior cruciate ligament
      (ACL) to receive either early (within 2 weeks) or delayed (8 to 12 weeks)
      reconstruction using a quadruple hamstring graft in order to determine if there
      was any functional advantage to early reconstruction. Outcome measures included
      return of knee movement, muscle dynamometry, International Knee Documentation
      Committee (IKDC) scores and Tegner activity levels. Two cases of symptomatic deep
      venous thrombosis occurred in the early group. The mean range of movement was
      significantly greater at two weeks in the delayed group. Quadriceps muscle power
      was significantly better in the delayed group at 12 weeks (p < 0.05). These
      trends were evident at later time points, but were not statistically significant.
      One patient in each group had clinically significant knee stiffness at 52 weeks.
      IKDC scores and Tegner activity levels were not significantly different at 52
      weeks. We conclude that there is no functional advantage to be gained by early
      reconstruction of the ACL.

PMID- 12793558
TI  - The influence of early ambulation and other factors on headache after lumbar
      myelography.
AB  - In order to determine the influence of early ambulation and other factors on
      headaches occurring after lumbar myelography we randomised 207 patients (127 men
      and 80 women) into two groups. Following the investigation, we allowed the 101
      patients (65 men and 36 women) in group A to sit or stand freely, while we
      confined the 106 patients (62 men and 44 women) in group B to bed for 20 hours.
      The nine patients in group B who could not maintain bed rest were excluded. There
      was no significant difference between the two groups as regards the prevalence of
      spinal headache (8.9% in group A v 14.4% in group B). Patients who reported
      headaches, however, were significantly more likely to be women (18.7%) than men
      (73%), be younger (mean age 45 years v 56 years), have a higher cerebrospinal
      pressure before removal of fluid (mean values 172 v 137 mm H2O) and a lower
      systolic (mean values 120 v 134 mmHg) and diastolic blood pressure. We conclude
      that, although other factors may be associated with headaches, late ambulation is
      not effective in preventing spinal headaches after lumbar myelography.

PMID- 12793557
TI  - Operative and functional treatment of rupture of the lateral ligament of the
      ankle. A randomised, prospective trial.
AB  - Consecutive patients with a confirmed rupture of at least one of the lateral
      ligaments of the ankle were randomly assigned to receive either operative or
      functional treatment. They were evaluated at a median of 8 years (6 to 11). In
      total, 370 patients were included. Follow-up was available for 317 (86%). Fewer
      patients allocated to operative treatment reported residual pain compared with
      those who had been allocated to functional treatment (16% versus 25%, RR 0.64, CI
      041 to 1.0). Fewer surgically-treated patients reported symptoms of giving way
      (20% versus 32%, RR 0.62, CI 0.42 to 0.92) and recurrent sprains (22% versus 34%,
      RR 0.66, CI 0.45 to 0.94). The anterior drawer test was less frequently positive
      in surgically-treated patients (30% versus 54%, RR 0.54, CI 0.41 to 0.72). The
      median Povacz score was significantly higher in the operative group (26 versus
      22, p < 0.001). Compared with functional treatment, operative treatment gives a
      better long-term outcome in terms of residual pain, recurrent sprains and
      stability.

PMID- 12793559
TI  - Survival analysis is a better estimate of recurrent disc herniation.
AB  - Studies on recurrent disc herniation quote rates of recurrence without regard to
      the times of recurrence and the influence of longer follow-up. Our objective was
      to assess the use of survival analysis to measure the rate of revision after
      lumbar microdiscectomy. We undertook a retrospective analysis of the hospital
      records of 993 patients who underwent lumbar microdiscectomy over a period of ten
      years. After calculating the overall rate of revision for the mean length of
      follow-up, we carried out a survival analysis using the life-table method. During
      the study period 49 patients had a revision microdiscectomy. This gave an overall
      rate of revision of 4.9% at a mean follow-up of 5.25 years. Using survival
      analysis, the rate of revision was 7.9% at a follow-up of ten years when the
      number at risk was 84. Survival analysis gives a more accurate estimation of the
      true rate of recurrence for patients undergoing lumbar microdiscectomy. The
      method allows better comparison between different interventions for disc
      herniation.

PMID- 12793560
TI  - Variation in the position and orientation of the elbow flexion axis.
AB  - We analysed the axis of movement in the normal elbow during flexion in vivo using
      radiostereometric analysis (RSA). The results show an intraindividual variation
      in the inclination of the axis ranging from 2.1 degrees to 14.3 degrees in the
      frontal and from 1.6 degrees to 9.8 degrees in the horizontal plane analysed at
      30 degrees increments. The inclination of the mean axis of rotation varied within
      a range of 12.7 degrees in the frontal and 4.6 degrees in the horizontal plane.
      In both planes, the mean axes were located close to a line joining the centres of
      the trochlea and capitellum. The intra- and interindividual variations of the
      axes of flexion of the elbow were greater than previously reported. These factors
      should be considered in the development of elbow prostheses.

PMID- 12793561
TI  - Os acromiale associated with tear of the rotator cuff treated operatively. Review
      of 33 patients.
AB  - Os acromiale is a rare anatomical abnormality and treatment is controversial. Our
      retrospective study analyses the outcome of excision, acromioplasty and bony
      fusion of the os acromiale when it is associated with a tear of the rotator cuff.
      After a mean follow-up of 41 months, 33 patients were radiologically and
      clinically assessed using the Constant score. The surgical procedure was to
      repair the rotator cuff together with excision of the os acromiale in six
      patients, acromioplasty in five, and fusion in 22. Of the 22 attempted fusions
      seven failed radiologically. The Constant scores were 82%, 81%, 81% and 84% for
      patients who had excision, acromioplasty, successful fusion and unsuccessful
      fusion respectively. There were no statistically significant differences. We
      conclude that a small mobile os acromiale can be resected, a large stable os
      acromiale treated by acromioplasty and a large unstable os acromiale by fusion to
      the acromion. Even without radiological fusion the clinical outcome can be good.

PMID- 12793562
TI  - Open treatment of anterior impingement of the ankle.
AB  - We assessed the long-term outcome ofopen debridement for the treatment of
      anterior impingement of the ankle in 27 patients. By using preoperative
      radiographs to group patients according to both the McDermott and the van Dijk
      scoring system, we assessed the accuracy of these classifications in predicting
      outcome. The Ogilvie-Harris scoring system, a visual analogue scale of patient
      satisfaction, the time to return to full activities, and the ability to return to
      sports determined the clinical outcome. Follow-up radiographs were used to assess
      the recurrence of osteophytes. We also assessed the incidence of talar
      osteochondral lesions at surgery. At a mean follow-up of 73 years, 23 of 25
      patients (92%) without joint-space narrowing had a good or excellent result.
      Improvement in the Ogilvie-Harris score was seen in all patients. In athletes, 19
      of 24 (79%) were able to return to sports at the same level. Two patients with
      preoperative joint-space narrowing had a poor result. Osteophytes usually
      recurred and most patients did not feel that the range of dorsiflexion returned
      to normal, but symptomatic relief allowed most to return to high-level sport. Our
      results for non-arthritic joints suggest that this is a safe and successful
      procedure.

PMID- 12793563
TI  - Orthotopic and heterotopic lower leg reimplantation. Evaluation of seven
      patients.
AB  - Reimplantation is a well-established procedure in reconstructive surgery. This is
      especially so after amputation of the upper limb since prostheses provide limited
      function. In unilateral amputation of the lower leg orthotopic reimplantation is
      the treatment of choice. With bilateral amputation, in which orthotopic
      reimplantation is not possible because of the complexity of the trauma,
      heterotopic reimplantation is an option. We report five patients who received
      orthotopic and two who received heterotopic reimplantations of the lower leg. We
      assessed the functional outcomewith reference to cutaneous sensation, mobility,
      pain, and the cosmetic result. The functional outcome was good, as was the
      patients' satisfaction. Their mobility, stability, and psychological state were
      satisfactory. Patients with heterotopic reimplantations preferred the reimplanted
      leg to a prosthesis. Although reimplantation of the lower leg requires prolonged
      hospitalisation, delayed mobilisation and secondary operations, we conclude that
      there is an indication for this operation in order to improve the patient's
      quality of life.

PMID- 12793564
TI  - Primary subacute epiphyseal and metaepiphyseal osteomyelitis in children.
      diagnosis and treatment guided by MRI.
AB  - We present three children with primary subacute epiphyseal and metaepiphyseal
      osteomyelitis. The diagnosis was delayed because of subtle radiological findings
      and mild general symptoms. Primary epiphyseal osteomyelitis is extremely rare. We
      believe that this is the first time that the MRI findings have been presented. In
      the first case they revealed a perforation into the knee and therefore an intra
      articular epiphyseal approach was used for debridement. In the second and third
      cases the metaepiphyseal lesions showed considerable physical involvement and a
      metaphyseal approach was chosen. We believe that in this condition MRI is
      essential both for diagnosis and in the planning of surgical treatment.

PMID- 12793565
TI  - Relapsed infantile Blount's disease treated by hemiplateau elevation using the
      Ilizarov frame.
AB  - We have treated seven children with relapsed infantile Blount's disease by
      elevation of the hemiplateau using the Ilizarov frame. Three boys and four girls
      with a mean age of 10.5 years were reviewed at a mean of 29 months after surgery.
      All had improved considerably and were pleased with the results. The improvements
      in radiological measurements were statistically significant (p < 0.001). Three
      dimensional CT reconstruction was useful for planning surgery. There were no
      major complications. The advantages of this technique are that in addition to
      elevation of the hemiplateau, rotational deformities and limb-length
      discrepancies may be addressed.

PMID- 12793566
TI  - Dynamic foot movement in children treated for congenital talipes equinovarus.
AB  - The aim of this study was to define objectively gait function in children with
      treated congenital talipes equinovarus (CTEV) and a good clinical result. The
      study also attempted an analysis of movement within the foot during gait. We
      compared 20 children with treated CTEV with 15 control subjects. Clinical
      assessment demonstrated good results from treatment. Three-dimensional gait
      analysis provided kinematic and kinetic data describing movement and moments at
      the joints of the lower limb during gait. A new method was used to study movement
      within the foot during gait. The data on gait showed significantly increased
      internal rotation of the foot during walking which was partially compensated for
      by external rotation at the hip. A mild foot drop and reduced plantar flexor
      power were also observed. Dorsiflexion at the midfoot was significantly
      increased, which probably compensated for reduced mobility at the hindfoot.
      Patients treated for CTEV with a good clinical result should be expected to have
      nearly normal gait and dynamic foot movement, but there may be residual intoeing,
      mild foot drop, loss of plantar flexor power with compensatory increased midfoot
      dorsiflexion and external hip rotation.

PMID- 12793567
TI  - Linear sebaceous naevus syndrome and resistant rickets.
AB  - The association between vitamin-D-resistant rickets and linear sebaceous naevus
      syndrome is extremely rare. Only eight cases have been described in the English
      literature and in none were the skeletal aspects addressed. We present three new
      cases and describe the musculoskeletal features. The details and outcome of
      surgery for correction of the deformities are discussed. The disturbances of
      metabolism of vitamin D and the effects of pharmacological treatment are also
      described.

PMID- 12793568
TI  - An unusual Monteggia type-I equivalent fracture in a child.
AB  - A six-year-old girl sustained a Monteggia type-I equivalent fracture of the right
      forearm. We describe the method of treatment of this rare fracture and its
      outcome.

PMID- 12793569
TI  - Electromagnetic augmentation of antibiotic efficacy in infection of orthopaedic
      implants.
AB  - Infection of orthopaedic implants is a significant problem, with increased
      antibiotic resistance of adherent 'biofilm' bacteria causing difficulties in
      treatment. We have investigated the in vitro effect of a pulsed electromagnetic
      field (PEMF) on the efficacy of antibiotics in the treatment of infection of
      implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips
      of stainless-steel pegs. They were exposed for 12 hours to varying concentrations
      of gentamicin or vancomycin in microtitre trays at 37 degrees C and 5% CO2. The
      test group were exposed to a PEMF. The control tray was not exposed to a PEMF.
      After exposure to antibiotic the pegs were incubated overnight, before standard
      plating onto blood agar for colony counting. Exposure to a PEMF increased the
      effectiveness of gentamicin against the five-day biofilms of Staphylococcus
      epidermidis. In three of five experiments there was reduction of at least 50% in
      the minimum biofilm inhibitory concentration. In a fourth experiment there was a
      two-log difference in colony count at 160 mg/l of gentamicin. Analysis of
      variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin
      which was significant at p < 0.05. There was no significant effect with
      vancomycin.

PMID- 12793570
TI  - Mechanical factors in the initiation and propagation of tears of the rotator
      cuff. Quantification of strains of the supraspinatus tendon in vitro.
AB  - Differential strain has been proposed to be a causative factor in failure of the
      supraspinatus tendon. We quantified the strains on the joint and bursal sides of
      the supraspinatus tendon with increasing load (20 to 200 N) and during 120
      degrees of glenohumeral abduction with a constant tensile load (20 to 100 N). We
      tested ten fresh frozen cadaver shoulders on a purpose-built rig. Differential
      variable reluctance extensometers allowed calculation of the strain. Static
      loading to 100 N or more increased strains on the joint side significantly more
      than on the bursal side. During glenohumeral abduction an increasing and
      significant difference in strain was measured between the joint and bursal sides
      of the supraspinatus tendon, which reached a maximum of 10.6% at abduction of 120
      degrees. The joint side strain of 7.5% reached values which were previously
      reported to cause failure. Differential strain causes shearing between the layers
      of the supraspinatus tendon, which may contribute to the propagation of
      intratendinous defects that are initiated by high joint side strains.

PMID- 12793571
TI  - Dorsal root ganglion neurones with dichotomising afferent fibres to both the
      lumbar disc and the groin skin. A possible neuronal mechanism underlying referred
      groin pain in lower lumbar disc diseases.
AB  - Dorsal root ganglion neurones with dichotomising axons are present in several
      species and are considered to play a role in referred pain. Clinically, patients
      with lesions in the lower lumbar discs occasionally complain of pain in the
      groin. We investigated the existence of dichotomising afferent neurones
      projecting axons both to the lumbar disc and to the groin skin, using the double
      fluorescent-labelling technique in rats. We observed neurones labelled with a
      tracer applied at the ventral portion of the LS-L6 disc and another tracer placed
      on the groin skin in L1 and L2 dorsal root ganglia. Our results showed that the
      double-labelled neurones had peripheral axons which dichotomised into both the LS
      L6 disc and the groin skin, indicating the convergence of afferent sensory
      information from the disc and groin skin. Our findings provide a possible
      neuroanatomical mechanism for referred groin pain in patients with disc lesions.

PMID- 12793572
TI  - Vascularity in a new model of atrophic nonunion.
AB  - Our aim was to develop a clinically relevant model of atrophic nonunion in the
      rat to test the hypothesis that the vessel density of atrophic nonunion reaches
      that of normal healing bone, but at a later time-point. Atrophic nonunion is
      usually attributed to impaired blood supply and is poorly understood. We
      determined the number of blood vessels at the site of an osteotomy using
      immunolocalisation techniques in both normally healing bones and in atrophic
      nonunion. At one week after operation there were significantly fewer blood
      vessels in the nonunion group than in the healing group. By eight weeks, the
      number in the atrophic nonunion group had reached the same level as that in the
      healing group. Our findings suggest that the number of blood vessels in atrophic
      nonunion reaches the same level as that in healing bone, but at a later time
      point. Diminished vascularity within the first three weeks, but not at a later
      time-point, may prevent fractures from uniting.

PMID- 12793573
TI  - The cortical thickness of the proximal humeral diaphysis predicts bone mineral
      density of the proximal humerus.
AB  - The operative treatment of fractures of the proximal humerus can be complicated
      by poor bone quality. Our aim was to evaluate a new method which allows
      prediction of the bone quality of the proximal humerus from radiographs.
      Anteroposterior radiographs were taken of 19 human cadaver humeri. The cortical
      thickness was measured at two levels of the proximal humeral diaphysis. The bone
      mineral density (BMD) was determined for the humeral head (HH), the surgical neck
      (SN), the greater tuberosity (GT) and lesser tuberosity (LT) using dual-energy x
      ray absorptiometry. The mean cortical thickness was 4.4 +/- 1.0 mm. Specimens
      aged 70 years or less had a significantly higher cortical thickness than those
      aged over 70 years. A significant positive correlation was found between cortical
      thickness and the BMD for each region of interest. The cortical thickness of the
      proximal diaphysis is a reliable predictor of the bone quality of the proximal
      humerus.

PMID- 12793574
TI  - The National Joint Registry for England and Wales.

PMID- 12793575
TI  - The natural history and treatment of rupture of the anterior cruciate ligament in
      children and adolescents.

PMID- 12793576
TI  - A randomised comparison of a foot pump and low-molecular-weight heparin in the
      prevention of deep-vein thrombosis after total knee replacement.

PMID- 12793578
TI  - Arthroplasty of the hip.

PMID- 12793577
TI  - Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome.

PMID- 12793580
TI  - Overt head movements and persuasion: a self-validation analysis.
AB  - The authors report 3 experiments that examine a new mechanism by which overt head
      movements can affect attitude change. In each experiment, participants were
      induced to either nod or to shake their heads while listening to a persuasive
      message. When the message arguments were strong, nodding produced more persuasion
      than shaking. When the arguments were weak, the reverse occurred. These effects
      were most pronounced when elaboration was high. These findings are consistent
      with the "self-validation" hypothesis that postulates that head movements either
      enhance (nodding) or undermine (shaking) confidence in one's thoughts about the
      message. In a 4th experiment, the authors extended this result to another overt
      behavior (writing with the dominant or nondominant hand) and a different attitude
      domain (self-esteem).

PMID- 12793579
TI  - When opportunity knocks: bottom-up priming of goals by means and its effects on
      self-regulation.
AB  - Four studies using general attribute goals or specific task goals revealed that
      attainment means cognitively activate the goals they are perceived to serve. A
      range of means replicated this effect including goal-directed activities,
      specific behavioral strategies, or opportunities, assumed to afford effective
      goal pursuit. The increased accessibility of a currently pursued goal due to
      "bottom-up" priming by its attainment means improved task persistence and
      performance, whereas a similarly increased accessibility of a competing goal
      impeded task persistence and performance.

PMID- 12793581
TI  - Transfer of value from fit.
AB  - People experience regulatory fit when they pursue a goal in a manner that
      sustains their regulatory orientation (E. T. Higgins, 2000). Five studies tested
      whether the value experienced from regulatory fit can transfer to a subsequent
      evaluation of an object. In Studies 1 and 2, participants gave the same coffee
      mug a higher price if they had chosen it with a strategy that fit their
      orientation (eager strategy/promotion; vigilant strategy/prevention) than a
      strategy that did not fit. Studies 3-5 investigated possible mechanisms
      underlying this effect. Value transfer was independent of positive mood,
      perceived effectiveness (instrumentality), and perceived efficiency (ease), and
      occurred for an object that w as independent of the fit process itself. The
      findings supported a value confusion account of transfer.

PMID- 12793582
TI  - Implicational schemata and the correspondence bias: on the diagnostic value of
      situationally constrained behavior.
AB  - Drawing on G. D. Reeder's (1993) schematic model of dispositional inference, it
      is hypothesized that perceivers' tendency to draw correspondent dispositional
      inferences from situationally constrained behavior (i.e., the correspondence
      bias) can be due to the application of schematic assumptions about trait-behavior
      relations (i.e., implicational schemata) within the process of situational
      adjustment. Applied to attitude attribution, situational adjustment is
      hypothesized to follow an implicit theory of ability, implying that only authors
      with a corresponding attitude are able to write a persuasive essay toward a given
      position. Results from 6 experiments offer converging evidence for this
      hypothesis. Implications for a sufficient understanding of the processes that
      lead to the correspondence bias are discussed.

PMID- 12793583
TI  - Adult attachment, the transition to parenthood, and depressive symptoms.
AB  - Testing a model suggested by J. Bowlby (1988), this study investigated how a
      personal vulnerability (attachment ambivalence) interacts with perceptions of
      deficient spousal support before and during a major life stressor (the transition
      to parenthood) to predict pre-to-postnatal increases in depressive symptoms.
      Highly ambivalent women who entered parenthood perceiving either less support or
      greater anger from their husbands experienced pre-to-postnatal increases in
      depressive symptoms at 6 months postpartum. The associations between these 2
      prenatal interaction terms and pre-to-postnatal increases in depressive symptoms
      were mediated by perceptions of declining spousal support across the transition
      period. Moreover, for highly ambivalent women, the association between prenatal
      and postnatal depression scores was mediated by perceptions of the amount of
      support available from their husbands.

PMID- 12793584
TI  - The self-fulfilling influence of mother expectations on children's underage
      drinking.
AB  - This research examined whether mothers' expectations about their children's
      drinking behavior influenced their children's future alcohol use through self
      fulfilling prophecies. It also investigated whether children's self-esteem,
      family social class, or the valence of mother expectations moderated this
      process. Analyses of longitudinal data from 505 mother-child dyads yielded
      results consistent with a self-fulfilling prophecy. The inaccurate portion of
      mother expectations predicted children's future alcohol use after accounting for
      relevant control variables. Moderation analyses indicated that this effect was
      stronger among higher self-esteem children and when mother expectations were
      positively valenced (i.e., when mothers underestimated their children's future
      alcohol use). The findings are discussed in terms of parent-child relationship
      quality, peer influences, self theories, and out-group stereotypes.

PMID- 12793585
TI  - My head says yes but my heart says no: cognitive and affective attraction as a
      function of similarity to the ideal self.
AB  - The authors hypothesized that similarity to the ideal self (IS) simultaneously
      generates attraction and repulsion. Attraction research has suggested that a
      person likes individuals who are similar to his or her IS. Social comparison
      research has suggested that upward social comparison threatens self-evaluation.
      In Experiment 1, attraction to a partner increased and then decreased as the
      partner became more similar to and then surpassed the participant's IS. In
      Experiment 2, the cognitive and affective components of attraction increased and
      decreased, respectively, as the partner approached and surpassed the
      participant's IS to the extent that the dimension of comparison was meaningful
      and participants andicipated meeting their partner. Similarity to the IS
      generates opposing cognitive and affective reactions when the self-evaluative
      threat of upward comparison intensifies.

PMID- 12793586
TI  - Attachment theory and group processes: the association between attachment style
      and group-related representations, goals, memories, and functioning.
AB  - Four studies examined attachment-style differences in group-related cognitions
      and behaviors. In Studies 1-2, participants completed scales on group-related
      cognitions and emotions. In Studies 3-4, participants were divided into small
      groups, and their performance in group tasks as well as the cohesion of their
      group were assessed. Both attachment anxiety and avoidance in close relationships
      were associated with negative group-related cognitions and emotions. Anxiety was
      also related to the pursuit of closeness goals and impaired instrumental
      performance in group tasks. Avoidance was related to the pursuit of distance
      goals and deficits in socioemotional and instrumental performance. Group cohesion
      significantly moderated the effects of attachment anxiety. The discussion
      emphasizes the relevance of attachment theory within group contexts.

PMID- 12793587
TI  - The do re mi's of everyday life: the structure and personality correlates of
      music preferences.
AB  - The present research examined individual differences in music preferences. A
      series of 6 studies investigated lay beliefs about music, the structure
      underlying music preferences, and the links between music preferences and
      personality. The data indicated that people consider music an important aspect of
      their lives and listening to music an activity they engaged in frequently. Using
      multiple samples, methods, and geographic regions, analyses of the music
      preferences of over 3,500 individuals converged to reveal 4 music-preference
      dimensions: Reflective and Complex, Intense and Rebellious, Upbeat and
      Conventional, and Energetic and Rhythmic. Preferences for these music dimensions
      were related to a wide array of personality dimensions (e.g., Openness), self
      views (e.g., political orientation), and cognitive abilities (e.g., verbal IQ).

PMID- 12793588
TI  - Perceived control and distress following sexual assault: a longitudinal test of a
      new model.
AB  - Longitudinal data were collected from female sexual assault survivors (N = 171)
      at 4 points postassault. Consistent with the predictions of the temporal model
      (P. Frazier, M. Berman, & J. Steward, 2002), past, present, and future control
      were differentially related to posttrauma distress. Both personal past
      (behavioral self-blame) and vicarious past (rapist blame) control were associated
      with higher distress levels. In addition, the belief that future assaults are
      less likely was more strongly associated with lower distress levels than was
      future control. Present control (i.e., control over the recovery process) was
      most adaptive. Hierarchical linear modeling analyses revealed that changes in
      perceived control were associated with changes in distress after linear change in
      distress over time was accounted for.

PMID- 12793589
TI  - Moral identity and the expanding circle of moral regard toward out-groups.
AB  - This article examines moral identity and reactions to out-groups during
      intergroup conflict Four studies suggest that a highly self-important moral
      identity is associated with an expansive circle of moral regard toward out-group
      members (Study 1) and more favorable attitudes toward relief efforts to aid out
      group members (Study 2). Study 3 examines moral identity and national identity
      influences on the provision of financial assistance to out-groups. Study 4
      investigates the relationship between moral identity and (a) the willingness to
      harm innocent out-group members not involved in the conflict and (b) moral
      judgments of revenge and forgiveness toward out-group members directly
      responsible for transgressions against the in-group. Results are discussed in
      terms of self-regulatory mechanisms that mitigate in-group favoritism and out
      group hostility.

PMID- 12793590
TI  - The aggression paradox: understanding links among aggression, sensation seeking,
      and the consideration of future consequences.
AB  - Four studies involving 573 female and 272 male college students demonstrated that
      multiple forms and measures of aggression were associated with high levels of
      sensation seeking, impulsivity, and a focus on the immediate consequences of
      behavior. Multiple regression analyses and structural equation models supported a
      theoretical model based on the general aggression model (C.A. Anderson & B.J.
      Bushman. 2002), positing that hostile cognition and negative affect mediate the
      relationships between the aforementioned individual differences and aggression.
      Sensation seeking also predicted a desire to engage in physical and verbal
      aggression. The final study demonstrated that relative to those scoring low,
      individuals scoring high on the consideration of future consequences are only
      less aggressive when aggression is likely to carry future costs.

PMID- 12793591
TI  - The interpersonal expression of perfection: perfectionistic self-presentation and
      psychological distress.
AB  - A concept involving the interpersonal expression of perfection, perfectionistic
      self-presentation, is introduced. It is argued that perfectionistic self
      presentation is a maladaptive self-presentational style composed of three facets:
      perfectionistic self-promotion (i.e., proclaiming and displaying one's
      perfection), nondisplay of imperfection (i.e., concealing and avoiding behavioral
      demonstrations of one's imperfection), and nondisclosure of imperfection (i.e.,
      evading and avoiding verbal admissions of one's imperfection). Several studies
      involving diverse samples demonstrate that perfectionistic self-presentation is a
      valid and reliable construct and a consistent factor in personal and
      interpersonal psychological distress. It is argued that the need to promote one's
      perfection or the desire to conceal one's imperfection involves self-esteem
      regulation in the interpersonal context.

PMID- 12793592
TI  - Metabolic syndrome: multiple candidate genes, multiple environmental factors-
      multiple syndromes?
AB  - Key elements of the metabolic syndrome include the development of insulin
      resistance, glucose intolerance, dyslipidaemia and hypertension, which lead to
      multiple effects on lipoprotein metabolism and vascular functions and, ultimately
      an increased risk of cardiovascular disease. There are probably multiple
      presentations of the metabolic syndrome, and these depend on the interplay of
      genetic variation and environmental factors. In particular, polymorphisms in
      genes that are expressed in adipose tissue may play a crucial role in the
      development of the metabolic syndrome. Elucidation of the aetiology of metabolic
      syndrome(s) will therefore play an important role in developing strategies to
      reduce adverse outcome. It is probable that pharmacological therapy will be
      needed for many patients with the metabolic syndrome to help reduce the risk of
      future cardiovascular events.

PMID- 12793593
TI  - Inflammation, the metabolic syndrome and cardiovascular risk.
AB  - Over the past ten years it has become clear that cardiovascular disease (CVD) and
      atherosclerosis have a 'microinflammatory' component and are often associated
      with low levels of inflammatory markers that are in the upper part of the
      'normal' range. In particular, diseases that predispose to CVD, such as the
      metabolic syndrome and type 2 diabetes, appear to have a very strong inflammatory
      component. While the inflammatory process is very complicated, single measures,
      such as C-reactive protein (CRP) or fibrinogen, have clear benefits as they
      summarise many different parts of the inflammatory process and are easy to apply.
      However, it is important to remember that the process of inflammation includes
      coagulation, fibrinolysis, complement activation, antioxidation, immune response
      and hormonal regulation through the hypothalamic-pituitary-adrenal axis.
      Furthermore, genetic variation, differences in exposure to environmental
      influences and the mass of inflammation-producing tissue (e.g. adipose tissue)
      can all influence responses. Thus, the relationship between atherosclerosis, the
      metabolic syndrome and inflammation is extraordinarily complex. Inflammatory
      markers such as CRP exhibit strong CVD-risk prediction that is consistent across
      sexes and a number of different populations. They reflect risk not only for
      'vulnerable plaque' and myocardial infarction (MI) but also for other
      cardiovascular diseases. In fact, inflammation is associated with several, if not
      all, of the chronic diseases of old age, and it is now clear that there are
      important links between inflammation and general metabolism. For instance,
      visceral adiposity exerts a major influence on inflammation status. Medications
      that affect atherosclerosis appear to do so at least in part by influencing
      inflammation (for instance, the emerging pleiotropic effects of statins), and
      this has far-reaching ramifications for chronic diseases of old age and their
      treatment.

PMID- 12793594
TI  - The relationship of obesity to the metabolic syndrome.
AB  - Obese patients with the metabolic syndrome generally have a visceral (apple
      shaped) fat distribution and are at an increased risk of macrovascular disease,
      while those with peripheral (pear-shaped) obesity tend not to have metabolic
      abnormalities and are at less risk. This difference appears to be related to the
      differing metabolic functions (and secretory products) of visceral adipose tissue
      (VAT) and subcutaneous adipose tissue (SAT), as well as the fact that VAT drains
      directly into the liver. Thus, it appears that increased VAT, but not SAT, is
      associated with both hepatic and peripheral biochemical abnormalities leading to
      insulin resistance and the associated metabolic syndrome. Insulin resistance is
      associated with VAT products, such as free fatty acids and their metabolites, as
      well as cytokines, such as tumour necrosis factor alpha (TNF-alpha). These
      factors may activate components of the inflammatory pathway such as nuclear
      factor kappa-B (NFkappaB), and inhibit insulin signalling. Insulin resistance is
      further associated with decreased levels of another tissue product, adiponectin.
      The incidence and prevalence of obesity is increasing at an unprecedented rate.
      The classic treatment of obesity is weight loss via lifestyle modification.
      However, prevention of obesity comorbidity can also be achieved by modifying the
      mechanisms by which obesity causes these comorbid conditions. For instance, it is
      now known that the peroxisome proliferator-activated receptor (PPAR) family of
      transcriptional regulators are crucial in regulating adipose tissue development
      and metabolism; this helps explain why compounds with PPARgamma agonist activity,
      e.g. thiazolidinediones, increase insulin action through their effects in
      regulating adipose tissue metabolism.

PMID- 12793595
TI  - Diet and exercise in the prevention of diabetes.
AB  - The worldwide epidemic of obesity is being mirrored in worldwide epidemics of
      metabolic syndrome and of type 2 diabetes. The theme of the 2002 Future Forum
      conference is that these conditions are a certainty, given that the changing
      worldwide environment requires less physical activity for daily living and
      assures an abundant, energy-dense food supply at all times. This paper focuses on
      the roles of physical activity and weight reduction in reducing the risk for
      development of type 2 diabetes and the metabolic syndrome. The mechanisms by
      which obesity and detraining lead to insulin resistance and type 2 diabetes are
      discussed and, conversely, the mechanisms by which insulin resistance might be
      reversed by physical activity are addressed. Finally, the evidence from recent
      randomised clinical trials is reviewed. The Finnish Diabetes Prevention Study and
      the Diabetes Prevention Program in the USA both demonstrate that lifestyle change
      can significantly reduce the risk of development of type 2 diabetes in
      individuals with impaired glucose tolerance. Furthermore, these studies
      demonstrate that modest weight change and achievable physical activity goals can
      translate into significant risk reduction. Societies cannot afford to ignore the
      evidence of health benefit associated with physical activity and healthy weight
      in favour of medicating when morbidities develop. For a successful public health
      approach to chronic disease prevention, we cannot rely completely on
      pharmaceuticals, but must implement environmental changes to encourage healthy
      lifestyles.

PMID- 12793596
TI  - PPAR agonists in the treatment of insulin resistance and associated arterial
      disease.
AB  - Augmented release of non-esterified fatty acids (NEFA) from insulin-resistant
      adipocytes appears to be the main cause of the 'atherogenic lipoprotein profile'
      associated with insulin resistance and type 2 diabetes. This atherogenic profile
      is characterised by large very-low-density lipoproteins (VLDL), small, dense low
      density lipoproteins (LDL) and low levels of high-density lipoproteins (HDL),
      resulting in deposition of apo B lipoproteins in the vascular intima and
      subsequent inhibition of reverse cholesterol transport. This lipoprotein
      retention also results in a proinflammatory response from the vascular
      endothelium, which is increased in insulin resistance. Thus the ideal therapy for
      insulin resistance, and its complications, should both improve its associated
      dyslipidaemia and ameliorate the vascular atherogenic reaction. Some peroxisome
      proliferator-activated receptor (PPAR)-gamma and dual PPARalpha/gamma agonists
      improve insulin resistance and its dyslipidaemia, both in rodents and man, while
      in animal models they can show clear antiatherosclerotic effects. Nonetheless, it
      is difficult to evaluate how much of these antiatherosclerotic actions are caused
      by effects on the dyslipidaemia or by direct effects on vascular cells.
      Upregulation of PPARgamma and PPARalpha/gamma activity in macrophages can reduce
      secretion of proinflammatory cytokines and matrix metalloproteases, as well as
      increase HDL-mediated cholesterol efflux transport--all potentially
      antiatherosclerotic results. In addition, treatment of smooth muscle cells with
      PPARgamma agonists can partially revert possible atherogenic changes in the
      production of matrix proteoglycans induced by exposure to NEFA. Although these
      findings are still preliminary, and their relevance to human atherosclerosis has
      not been fully elaborated, these results suggest that improved PPARalpha/gamma
      agonism may positively modulate several of the metabolic steps connecting insulin
      resistance with dyslipidaemia and with the atherogenic response.

PMID- 12793597
TI  - What future for combination therapies?
AB  - For most patients who require lipid-lowering treatment, statin monotherapy is the
      appropriate treatment. However, in those patients where statin monotherapy does
      not produce optimal lipid levels, the combination of a statin with niacin, a bile
      acid sequestrant, a fibric acid derivative, a cholesterol absorption inhibitor or
      a fish oil preparation may provide improved control. The choice of combination
      therapy depends upon the patient's lipid profile and tolerability of the
      medication. Combination of a statin with niacin, a bile acid sequestrant or
      ezetimibe, a cholesterol absorption inhibitor, should be considered for patients
      with very high low-density lipoprotein cholesterol (LDL-C) levels, while
      combination with either a fibric acid derivative or a fish oil should be
      considered for patients with high LDL-C and high triglyceride levels. A number of
      new lipid-lowering agents are currently in development, including cholesteryl
      ester transfer protein (CETP) inhibitors, acyl coenzyme A: cholesterol
      acyltransferase (ACAT) inhibitors, ileal bile acid transport (IBAT) inhibitors,
      microsomal triglyceride transfer protein (MTP) inhibitors and dual peroxisome
      proliferator-activated receptor (PPAR) alpha and gamma agonists. Introduction of
      these novel therapies will provide opportunities for developing different
      combination strategies that may help to optimise lipid profiles in patients who
      are currently difficult to treat. The introduction of new combinations will
      require careful study to ensure that the risks of drug interactions and adverse
      events are minimised.

PMID- 12793598
TI  - Role of statin pleiotropism in acute coronary syndromes and stroke.
AB  - Several landmark clinical trials have demonstrated the benefit of lipid-lowering
      with statins for the primary and secondary prevention of coronary heart disease.
      The clinical data in support of lowering cholesterol by statins are unequivocal.
      The established mechanism of action is via sterol regulatory element binding
      protein (SREBP) activation due to reduced hepatic cholesterol synthesis and
      secondary upregulation of the low-density lipoprotein (LDL)-receptor, leading to
      enhanced clearance of circulating cholesterol and lipids. Although it is widely
      accepted that most clinical benefit obtained with statins is a direct result of
      their lipid-lowering properties, there is still some debate as to whether the so
      called 'pleiotropic effects' of statins contribute to the clinical outcome in
      vascular disease, or whether all the beneficial effects of statins are simply due
      to lipid-lowering. For example, these agents appear to display additional
      cholesterol-independent effects on various aspects of cardiovascular disease,
      including improving endothelial function, decreasing vascular inflammation and
      enhancing plaque stability. Thus, further studies are needed to understand the
      full impact of statin therapy on each of these processes and whether these
      effects contribute to the clinical benefits of statins in acute coronary
      syndromes and stroke.

PMID- 12793599
TI  - Congenital malformations and developmental changes of the breast: a
      neonatological view.
AB  - Congenital malformations of the breast and nipple-areolar complex are described
      from the aspect of neonatal dysmorphology. Their classification is based on the
      accepted nomenclature in the medical literature and on a special method of
      clinical examination. The embryology and the possible genes involved in breast
      development are also discussed to clarify the mechanisms underlying the
      occurrence of breast malformations. Except for amastia, polymastia and
      polythelia, which have received much attention, the data for many other breast
      malformations are sparse. Case control studies or even case series are rare, and
      good evidence is often lacking. In addition, more studies are needed to complete
      the map of genes involved in breast development. This information will contribute
      substantially to our understanding and clinical approach to breast malformations
      in the future.

PMID- 12793600
TI  - Pediatric endocrine diseases in pre-Hispanic Aztecs.
AB  - Aztec medical and religious knowledge derived from Olmecs (800 BC), Teotihuacans
      (100 BC) and Toltecs (1100-1521 AC); however, there is no unique source that
      accurately presents Aztec medicine. Sahagfin combines naturalism and religion but
      not magic ("First Memorials", "Matritense Codex", "Florentine Codex" and "General
      History of New Spain"); Hernandez gives a naturalistic image but is full of
      mistakes ("Natural History of the New Spain"); Badiano tries to match Aztecs with
      contemporary Europeans and with the first century medicine of the Romans
      ("Badiano Codex"), and Ruiz de Alarcon contains plenty of magical concepts ("Book
      of Superstition"). For the Aztecs, surveillance of growth was very important and
      represented a balance between body and soul. They described the different steps
      of pubertal development. They had specific treatments for thyroid disease in
      children, mainly hypothyroidism and goiter. There are no references to rickets,
      nor to type 1 or 2 diabetes mellitus.

PMID- 12793601
TI  - Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after
      vaccination is consistent with clustering after infections and progression to
      type 1 diabetes mellitus in autoantibody positive individuals.
AB  - OBJECTIVE: We previously analyzed data from a hemophilus vaccine trial and
      identified clusters of extra cases of type 1 diabetes mellitus (T1DM) caused by
      the vaccine that occurred between 36 and 48 months after immunization. Published
      reports indicate clustering of cases of T1DM occurring approximately 2-4 years
      after mumps infection. Others have reported a 2-4 year delay between the onset of
      autoantibodies and the development of T1DM. We attempted to determine whether
      similar clustering of cases of T1DM occurred after immunization with vaccines
      other than hemophilus. METHODS: We searched MEDLINE and reviewed references from
      published papers to find databases on the incidence of T1DM and then searched
      MEDLINE to determine whether changes in immunization occurred in these regions
      during the times the incidence of DM was being recorded. RESULTS: Distinct rises
      in the incidence of T1DM occurred 2-4 years following the introduction of the MMR
      and pertussis vaccines. A drop in the incidence of T1DM was detected between 3-4
      years following discontinuation of pertussis and BCG vaccines. CONCLUSION: The
      identification of clusters of cases of T1DM occurring in consistent temporal time
      periods allowed a link between the hemophilus vaccine and T1DM to be established.
      The current findings indicate the there are also clusters of cases of T1DM
      occurring 2-4 years post-immunization with the pertussis, MMR, and BCG vaccine.
      The data are consistent with the occurrence of clusters following mumps infection
      and the progression to T1DM in patients with antipancreatic autoantibodies.

PMID- 12793602
TI  - Effects of insulin-like growth factor-I deficiency and replacement therapy on the
      hematopoietic system in patients with Laron syndrome (primary growth hormone
      insensitivity).
AB  - BACKGROUND: Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in
      Laron syndrome (LS), are a unique model in man to study the consequences
      resulting from defects in growth hormone (GH) signal transmission. OBJECTIVE: To
      assess retrospectively the effect of IGF-I deficiency and its therapy on the
      various cells of the hematopoietic system as reflected by peripheral blood
      counts. PATIENTS AND METHODS: Two groups of patients were studied. The first
      group consisted of 11 untreated patients with LS, seven males and four females,
      who were followed from childhood into adult age. Average age at the time of data
      analysis was 45.4 +/- 9.6 years. The second group included ten children with LS,
      six males and four females, who received IGF-I replacement therapy for an average
      period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation
      of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or
      more were included in the analysis. Data on blood counts were collected from the
      patients' charts. Blood samples were drawn at baseline, weekly during the first
      month, once a month during the first year, and once every 3 months thereafter.
      Statistical analysis of the change over time was performed using repeated
      measures ANOVA. RESULTS: Children with LS had red cell indices in the lower
      normal range and an elevated monocyte count. A statistically significant rise in
      red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose
      from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl
      to 13.01 g/dl (p < 0.001); hematocrit from 34.94% to 38.52% (p = 0.007), and mean
      corpuscular volume from 72.27 fl to 79.93 fl (p < 0.001). The platelet count
      diminished significantly during IGF-I therapy from 316 x 10(3)/ml to 219 x
      10(3)/ml (p = 0.02), and the monocyte count from 0.74 x 10(3)/ml to 0.49 x
      10(3)/ml (p < 0.001). CONCLUSIONS: The present investigation, the first of its
      kind in this syndrome, confirms that IGF-I has a strong stimulatory effect on
      erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and
      platelets, an effect not previously described. The mechanism by which IGF-I
      mediates these effects needs further elucidation.

PMID- 12793603
TI  - Thyroid hormone synthesis and storage in the thyroid gland of human neonates.
AB  - The aim of this study was to evaluate the morphological and biochemical
      maturation of the thyroid gland in human neonates. The mean iodine concentration
      in the thyroid gland of very premature infants (less than 32 weeks gestational
      age, 0-3 days survival, n = 12) was significantly lower than in the older group
      (34-41 weeks gestational age, 0-30 days survival; n = 15; p < 0.05). For the
      whole group of neonates there was a statistically significant linear correlation
      between duration of life, i.e. gestational age and survival, and iodine
      concentration (r = 0.64, p < 0.01). Although there was wide dispersion of the
      results the same tendency was seen for thyroglobulin (Tg) concentration in the
      thyroid gland (r = 0.52, n = 21; p < 0.05). Comparative histological examination
      of the fetal thyroids gave results in accordance with the biochemical data as
      intrafollicular colloid appeared to be more abundant in more mature thyroids. The
      iodine content in Tg was found to be 0.63 +/- 0.22% in very preterm neonates and
      was slightly but not significantly lower than that found in the thyroids of the
      older group (0.82 +/- 0.14%; p = 0.055). The content of T4 and T3 per Tg molecule
      in the neonates was related to the iodine content. The differences in mean values
      of T4/Tg and T3/Tg molar ratios between the two groups were not significant: T4:
      2.8 +/- 1.8 mol/ mol, T3: 0.29 +/- 0.12 mol/mol in very preterm neonates; and T4:
      3.5 +/- 0.7 mol/mol, T3: 0.34 +/- 0.09 mol/mol in the older group. These results
      offer useful information for further analysis of the development of thyroid
      function in the human neonate.

PMID- 12793605
TI  - Measured length of normal term infants changes over the first two days of life.
AB  - Measured neonatal length may be influenced by reluctance of the measurer to
      extend the infant's limbs against the normal flexor posture. As the degree of
      flexion decreases over the first few days of life, measured length may increase.
      We conducted a study of the effect of postnatal age on measured length and on
      inter-observer correlation. The study sample consisted of 101 healthy term
      newborns. Correlation between measurements made before age 2 hours by the study
      nurse and by regular nurses was excellent with a mean difference of 0.61 +/- 0.49
      cm (r2 = 0.923). The mean measured length increased by 0.2 cm between admission
      and age 1 day (p = 0.057) and by a further 0.17 cm by age 2 days (p = 0.001).
      This study demonstrates that measured length appears to change over the first 2
      days of life.

PMID- 12793604
TI  - Bisphosphonates, a new treatment for glucocorticoid-induced osteoporosis in
      children.
AB  - BACKGROUND: Long-term corticoids used as a treatment for rheumatic diseases are
      the most frequent cause of osteoporosis in the pediatric population.
      Bisphosphonates have been proved to be useful in treating osteoporosis.
      OBJECTIVE: To investigate the efficacy of pamidronate in corticoid-induced
      osteoporosis in children. PATIENTS AND METHODS: Ten children affected with
      rheumatic diseases and osteoporosis underwent biannual cycles of intravenous
      pamidronate (4 to 12 cycles). Complete clinical, radiological, biochemical and
      densitometric follow-up was performed at every treatment cycle. RESULTS: Good
      clinical and radiological evolution was observed in most of our patients; no new
      vertebral fractures were reported. Good densitometric evolution has been linked
      to the onset of puberty (rise in IGF-I levels) and low values for inflammatory
      activity markers (ESR and CRP). Self-limited hyperthermia and mild abdominal pain
      were observed during pamidronate infusion, but no other side effects were
      reported. CONCLUSIONS: Pamidronate is a safe and useful treatment for corticoid
      induced osteoporosis in the pediatric population.

PMID- 12793606
TI  - Validity of the use of a few hand-wrist bones for assessing bone age.
AB  - Bone age is widely used as an osseous maturation method to assess biological
      development in clinical and auxological studies. Numerical methods for
      calculating bone age have better replicability; however, they require a wide data
      manipulation. The aim of this study was to evaluate the accuracy of bone age
      estimation by using just a few ossification centers. In 205 hand and wrist
      radiographs of children and adolescents, aged 0.9-17.4 years old (111 males and
      94 females), bone age was determined by two trained observers employing the five
      bone (B5) and the TW2 methods. To compare the results of the two methods, the
      mean differences by age and sex were tested by the Mann-Whitney test. The
      relationship of the bone age distribution estimated by B5 and TW2 was calculated
      and the mean of the bone age determined by the two methods was plotted by age and
      by differences between bone age calculated by the two methods +/- 2 SD. The bone
      age determined by B5 was between 1.2 and 16.8, and by TW2 was between 1.2 and
      18.0 years. The mean differences between B5 and TW2 (-0.06 +/- 0.6) were not
      significant (p > 0.05). The distribution of mean differences by age and method
      demonstrated that all deviations were encompassed into +/- 2 SD with no
      particular bias. In general terms, a good agreement was obtained between these
      two methods.

PMID- 12793607
TI  - Dissatisfactioin with height and weight, and attempts at height gain and weight
      control in Korean school-children.
AB  - Most students are reported to be dissatisfied with their height and weight. The
      current study was designed to assess the prevalence of height and weight
      dissatisfaction and specific height-gain and weight-control attempts in school
      children in Korea. A questionnaire survey was carried out in 3,382 students aged
      11-18 years. The prevalence of dissatisfaction with height and weight was
      significantly higher in girls than in boys. High school students were more
      dissatisfied with their height and weight than elementary school students. The
      concordance rates between perceived vs actual height and weight were 30% and 45%,
      respectively. The average desired adult height was 8-9 cm taller than the average
      Korean adult height. The average desired adult weight was 4.9 kg more in boys,
      and 4.8 kg less in girls, than the current average Korean adult weight.
      Approximately 4.4-7.3% of overall school-children had tried to promote their
      growth. The prevalence of height-gain attempts was highest in middle school
      students, and the prevalence of weight-control attempts was highest in high
      school students. Among the height-gain methods, herbal medicine was most
      frequently used (46.4%), followed by growth-promoting health supplements (27.4%)
      and growth hormone (3.2%). For weight control, exercise at a fitness center was
      more favored (54.5%) than herbal medicine (17.5%) or diet drugs (13.0%). In
      conclusion, the prevalence of height and weight dissatisfaction was high and many
      students made attempts at height gain and weight control. These data emphasize
      the importance of health education about body image to students.

PMID- 12793609
TI  - Testicular descent related to growth hormone treatment.
AB  - An 8.7 year-old boy with cryptorchidism and growth hormone (GH) deficiency due to
      septooptic dysplasia presented testicular descent related to the commencement of
      hGH treatment. This case suggests a role for GH in testicular descent.

PMID- 12793608
TI  - Insulin resistance and hyperinsulinemia in prepubertal obese children.
AB  - BACKGROUND: Tissue resistance to insulin has been demonstrated in obese
      individuals. Pancreatic beta-cells respond to the reduced tissue sensitivity with
      increased insulin secretion so that glucose homeostasis is maintained. OBJECTIVE:
      The purpose of this prospective study was to investigate the presence of
      hyperinsulinemia and insulin resistance in obese children and adolescents.
      SUBJECTS AND METHODS: Fasting glucose (FG) and insulin (FI) levels and fasting
      glucose to insulin ratio (FGIR) were measured in 26 obese prepubertal children
      and 20 obese adolescents, as compared to 20 non-obese prepupertal children and 20
      adolescents with normal body weight. Furthermore, obese children and adolescents
      underwent an oral glucose tolerance test with measurements of glucose and insulin
      2 hours post glucose load. RESULTS: In 14/26 (54%) obese prepubertal children and
      in 16/20 (80%) obese adolescents FI was >24 microU/ml. FGIR was <6 in 23/26 (88%)
      prepubertal obese children and in all obese adolescents. All non-obese
      prepubertal children and adolescents had normal FI. However, FGIR was <6 in 6/20
      (30%) non-obese prepubertal children and in 15/20 (75%) non-obese adolescents.
      CONCLUSION: Hyperinsulinemia and insulin resistance are already present in
      prepubertal obese children. As hyperinsulinemia is a potentially reversible
      condition and the complications related to it may be prevented, early
      measurements should be undertaken so that obese children lose body weight before
      the onset of puberty which may enhance the problem of insulin insensitivity.

PMID- 12793610
TI  - Monozygotic twins with congenital adrenal hyperplasia: long-term endocrine
      evaluation and gene analysis.
AB  - Monozygotic female twins with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency are described and evaluated over the first 6 years of
      life. Despite appropriate steroids, NaCl, and fludrocortisone therapies, there
      was significant fluctuation in the suppression of adrenal steroid secretion.
      Advanced bone maturation in both was noted. For the first time, molecular genetic
      analysis was performed and documented that the twins were compound heterozygotes
      for two different mutations: the maternal allele carried the 8-bp deletion
      mutation, whereas the paternal allele carried the 1172N missense mutation.
      Parental DNA samples confirmed that the mutations were on different alleles.

PMID- 12793611
TI  - Adult type granulosa cell tumor causing precocious pseudopuberty in a 6 year-old
      girl.
AB  - Malignant ovarian tumors are responsible for 2-3% of all cases of precocious
      pseudopuberty (PP) in girls. The most common forms of ovarian tumors presenting
      as PP are the granulosa cell tumors (GCT). The clinical and pathological features
      of granulosa cell tumors that occur frequently in young girls, so-called juvenile
      granulosa cell tumors (JGCT), differ histologically from those occurring in
      adults. As a cause of PP in young girls, adult type granulosa cell tumors (AGCT)
      are extremely rare. We report a 6 year-old girl presenting with early breast
      development and vaginal bleeding due to a well encapsulated ovarian tumor.
      Microscopic features of the resected tumor were characteristic of AGCT.

PMID- 12793613
TI  - Evaluation and initial management of the patient in respiratory distress.
AB  - Evaluation of the patient in acute respiratory distress poses a complex problem
      to the emergency physician. Because of the heterogeneity of the population of
      patients presenting in acute respiratory distress, there is a paucity of evidence
      based medicine recommendations. Practice habit dictates most of our diagnostic
      and therapeutic approach. It is of paramount importance to understand the
      limitations of history, physical examination, and diagnostic screening studies in
      evaluating and treating patients with respiratory distress. The emergency
      physician should become aware of the benefits of NPPV in the management of
      respiratory failure. Essential to the management of these patients is the ability
      to anticipate difficulty in airway management and the formulation of alternative
      airway strategies.

PMID- 12793612
TI  - True hermaphroditism in an XY individual due to a familial point mutation of the
      SRY gene.
AB  - A number of genes are known to control the development of the testis but the
      transcription factor SRY encoded on the Y-chromosome is considered to play the
      major role in initiating the first step in determining testicular
      differentiation. Mutations in this gene usually result in gonadal dysgenesis, but
      it is interesting to note that at least three of these mutations have been found
      to be familial. Furthermore, fewer than 10% of true hermaphrodites carry an XY
      karyotype, and so far only two patients have been documented to carry a mutation
      in the SRY gene. We have identified a familial mutation in the SRY gene involving
      a previously described locus. The index patient was born with severely ambiguous
      genitalia and on histological examination the gonads revealed true
      hermaphroditism, containing ovarian as well as testicular tissue. The father, his
      three brothers, and his first-born son carry the identical mutation. The severely
      feminized XY individual was diagnosed shortly after birth, gonadectomized and
      raised as female. SRY was determined by PCR and subsequently sequenced using
      cycle sequencing. A previously published point mutation was identified at
      nucleotide position 680 resulting in a non-conservative exchange of the amino
      acid iso-leucine at position 90 into methionine. This position represents a
      mutational 'hot spot', which seems to retain a certain amount of protein
      activity, enabling normal male development in some individuals. The patient is
      the third one reported in whom a mutation in the SRY gene results in ovarian-like
      development. Since ovarian development in XY individuals is extremely rare, its
      mechanism is of great interest. Further studies in this family might allow the
      identification of factors initiating and stimulating ovarian development. How far
      these infantile ovaries would have developed normally, however, is merely
      speculative.

PMID- 12793614
TI  - Management of the difficult airway: alternative airway techniques and adjuncts.
AB  - Rapid-sequence intubation using conventional laryngoscopic technique remains the
      standard of airway management in emergency medicine and continues to have a
      success rate of approximately 98%. Preparation and proper intubation technique
      must be optimized at the initial attempt using direct laryngoscopy. Failure
      causes multiple repeated attempts, leading to a failed airway. Each repeated
      attempt increases the likelihood of bleeding, oral, pharyngeal, and laryngeal
      edema, and malposition, causing decreased visualization of the glottic opening,
      equipment failure, and hypoxia. Preparation must be an ongoing process. Faulty
      suction, no oxygen source, choice of the wrong laryngoscopic blade or ETT, poor
      light source, or misplaced equipment can domino into mechanical failure.
      Intubation equipment stations must be inventoried constantly, organized, and kept
      simple in their layout to decrease confusion during selection. Medication for
      sedation and paralysis should be readily available and not kept distant from the
      intubation station in a medication-dispensing unit that would require time for
      acquisition. Proper positioning of the patient remains paramount for alignment of
      the oral, pharyngeal, and laryngeal axis to provide optimal visualization of the
      vocal cords. Proper technique during insertion of the laryngoscope blade in the
      oral cavity for displacement of the tongue must be ensured. Without proper
      technique, even with proper positioning, the glottic opening cannot be
      visualized. Laryngeal pressure to maneuver the larynx into position should be
      exerted initially by the laryngoscopist's right hand and, when in view,
      maintained by an assistant to free the laryngoscopist's hand for ETT insertion.
      With preparation and proper technique, the first attempt is the best attempt, and
      the vicious cycle of multiple attempts and complications will be averted.

PMID- 12793615
TI  - Pulmonary trauma emergency department evaluation and management.
AB  - Pulmonary trauma is a significant cause of morbidity and mortality in the United
      States. It is imperative for the emergency physician to identify promptly
      patients who require immediate therapy. In patients who have limited injuries,
      literature shows that often conservative management provides improved outcome. As
      the exposure to automobiles and firearms continues to increase in the setting of
      improved prehospital management, the emergency physician will encounter an
      increasing amount of pulmonary trauma. This rise in respiratory injuries will
      require a more aggressive approach of patients with minimal morbidity and
      mortality. A systematic approach to respiratory injuries is crucial to improving
      patient outcomes.

PMID- 12793616
TI  - Asthma evaluation and management.
AB  - Asthma is a chronic inflammatory illness with acute exacerbations, which often is
      encountered in the ED setting. Knowledge of the presentation and treatment of
      asthma is crucial for any physician treating patients with this disease. Beta
      agonist, anticholinergic, and corticosteroid therapy continue to be the mainstay
      of emergency therapy despite advances in newer medications. Proper attention to
      long-term treatment of asthma and aggressive treatment of acute exacerbations
      should help reduce morbidity and mortality.

PMID- 12793617
TI  - Acute exacerbations of chronic obstructive pulmonary disease.
AB  - This article discusses the definition, pathophysiology, cause, clinical
      presentation, laboratory work-up, and treatment of chronic obstructive pulmonary
      disease (COPD) exacerbation. The focus is on the presentation of acute
      exacerbations of COPD in the emergency department and the available evidence for
      testing and treatment.

PMID- 12793618
TI  - Influenza.
AB  - Influenza is a major killer and world health problem. Infection rates are highest
      in children, but complication rates are highest in the elderly, patients with
      chronic pulmonary and cardiovascular disease, immunosuppressed patients, and
      diabetics. Widespread vaccination, particularly of individuals at high risk, is
      crucial in decreasing incidence, controlling epidemics, and reducing
      complications. A new class of antiviral drugs, the neuraminidase inhibitors, has
      been shown to be effective in reducing time to alleviation of symptoms, close
      contact prophylaxis, and reducing complications of high risk individuals.

PMID- 12793619
TI  - Pulmonary embolism.
AB  - PE is one of the great challenges in medicine. It is a disease that carries with
      it a high mortality rate, yet no historical piece of information, physical
      examination finding, or diagnostic modality is perfect at excluding its
      possibility. Emergency physicians must be vigilant about considering PE in the
      differential diagnosis of a variety of presenting complaints and must use a
      variety of diagnostic and therapeutic options as they manage patients with
      suspected or confirmed PE. The diagnostic options range from bedside diagnostic
      tests to highly specialized imaging available at only specialized institutions.
      Knowing the advantages and disadvantages of each of the diagnostic modalities
      assists the physician in employing the best test. Therapeutic options also vary
      widely and include anticoagulation, vena caval interruption, systemic
      thrombolysis, embolectomy, and other therapeutic adjuncts, such as ECMO and
      inhaled nitric oxide. Similarly, awareness of the indications and
      contraindications to the varied therapeutic agents ensures appropriate therapy
      when the diagnosis is made.

PMID- 12793620
TI  - Noncardiogenic pulmonary edema.
AB  - Pulmonary edema is differentiated into two categories--cardiogenic and
      noncardiogenic. Noncardiogenic pulmonary edema is due to changes in permeability
      of the pulmonary capillary membrane as a result of either a direct or an indirect
      pathologic process. It is a spectrum of illness ranging from the less severe form
      of ALI to the severe ARDS. The mainstay of treatment is mechanical ventilation
      with maximization of ventilation and oxygenation through the judicious use of
      PEEP. Newer ventilation techniques, such as high-frequency oscillatory
      ventilation and partial fluid ventilation, are promising but are in the early
      stages of clinical testing. Mortality rates remain high despite increasing
      intensive care unit care.

PMID- 12793621
TI  - Community-acquired pneumonia in the emergency department: a practical approach to
      diagnosis and management.
AB  - Pneumonia is one of the most common conditions for which patients seek emergency
      care. It is a challenging infection in that the spectrum of illness ranges from
      the nontoxic patient appropriate for outpatient antibiotics to the critically ill
      patient requiring intensive care hospitalization. Current data and diagnostic
      technology provide the emergency physician with the tools for an appropriately
      rapid evaluation and consideration of the differential diagnosis. Key critical
      thinking and application of published findings allow for intelligent empirical
      antibiotic treatment and risk stratification for the best disposition. Although
      antibiotic-resistant organisms increasingly are being identified, patients
      continue to benefit from early institution of standard ED treatment. Coverage for
      atypical organisms improves patient response and outcome. Finally, identification
      and treatment of the complications of pneumonia and accompanying sepsis must be
      considered by the ED physician when evaluating critically ill patients.

PMID- 12793622
TI  - Hemoptysis.
AB  - Hemoptysis is a common complaint the emergency physician encounters. Most cases
      are minor and treatable or self-limited. In many cases a cause is never
      determined. Massive hemoptysis is an occasional occurrence that must be assessed
      and managed swiftly. The initial approach is no different than that for any
      bleeding or respiratory or hemodynamically unstable patient. The emergency
      physician must stabilize, localize, and stop bleeding, and include required
      specialists to achieve that purpose. The management suggestions presented in this
      article are simplistic. The emergence of improved CT technology and new
      bronchoscopic and angiographic techniques has provided safe and effective
      alternatives to surgery for many causes of hemoptysis. Surgery, however,
      continues to be the treatment of choice for some. Being familiar with the broad
      list of causes is imperative to keeping an approach organized.

PMID- 12793623
TI  - Pediatric pneumonia.
AB  - Respiratory disease is common in pediatrics and diagnosing pneumonia may be
      clinically challenging. Changes in pneumococcal resistance and immunization
      practices continue to change the incidence and etiologies of pneumonia. Careful
      attention to epidemiologic, seasonal, and specific pediatric clinical factors and
      using adjunct radiographs and laboratory tests should guide the emergency
      physician in his or her management strategy, including selection of antibiotics
      and inpatient or outpatient disposition.

PMID- 12793624
TI  - Positive pressure mechanical ventilation.
AB  - There have been numerous advances in the application of positive pressure
      mechanical ventilation in the last two decades. As knowledge of pulmonary
      physiology expands, the application of modes and parameters to maximize the
      efficacy and minimize the complications of ventilatory support continues to
      advance. As the use of noninvasive ventilation becomes more widespread, its
      usefulness in certain clinical entities such as COPD exacerbations and acute
      cardiogenic pulmonary edema will become more prominent. The role of specific
      modes and parameters of these devices likely will be further refined to maximize
      outcomes.

PMID- 12793625
TI  - Environmental insults: smoke inhalation, submersion, diving, and high altitude.
AB  - In the expanding search for recreation, we spend more and more of our time in
      various environments. Whether the air is thin or compressed or smoke-filled or
      there is no air at all, emergency physicians continue to meet and treat the
      various pulmonary emergencies that the environment may create. The authors
      present the background, diagnosis, and management of a few of the more common
      pulmonary emergencies that the environment may produce.

PMID- 12793626
TI  - Pulmonary considerations in the immunocompromised patient.
AB  - The compromised patient who presents to the emergency department with pulmonary
      complaints is becoming a common occurrence. An immunocompromised state can result
      from a disease process such as HIV or from medications used to prevent graft
      rejection in solid organ recipients or to treat conditions such as collagen
      vascular disease. The emergency department physician should be familiar with the
      more common complications that can afflict this unique patient group. This
      article addresses the presentation, evaluation, and treatment of the more common
      pulmonary complications that can occur in solid organ transplant recipients,
      cancer patients, patients suffering from collagen vascular disease, and patients
      with HIV disease.

PMID- 12793627
TI  - Acute inhalation injury.
AB  - The lungs can be an efficient means for the absorption of inhaled toxicants,
      resulting in airway and pulmonary injury or systemic toxicity. Although a few
      specific antidotes exist for inhaled toxicants, the syndrome of acute inhalation
      injury and clinical therapeutics are linked by common pathways of
      pathophysiology. Understanding the mechanisms of inhalation injury and occupation
      or situation-specific toxicants can simplify the decision-making process for the
      out-of-hospital emergency responder and the emergency physician when confronted
      with a patient and the myriad of potential inhaled toxicants.

PMID- 12793628
TI  - Medicolegal issues in medical practice.

PMID- 12793629
TI  - Medicolegal aspects in medical practice.

PMID- 12793631
TI  - Rape-law and woman's right--critical analysis vis-a-vis role of attending doctor.
AB  - According to Supreme Court rape is not only a crime against entire society, it
      destroyes the entire psychology of woman and pushes her into deep emotional
      crisis. The need at present is to mould and evolve the rape-law so as to make it
      more sensitive and responsive to the demands of the time in order to resolve the
      basic problem. The rape-laws have some lacunae which need a fresh look for
      necessary changes. The necessary changes can be suggested and made in relation to
      sexual intercourse, age of the rape victim, genital tract defects in woman, HIV
      infection, injury inflicted on the victim with corroboration of evidence and
      circumstances which must be supervised with high precaution. It must be
      remembered that doctors and scientific experts play most crucial and vital role
      and ignorance of rape-law and lack of high degree expertise skill can make the
      accused easily set at liberty.

PMID- 12793630
TI  - Application of DNA fingerprinting in medicolegal practice.
AB  - Fingerprinting is thought to establish the identify of an individual in forensic
      cases. The technique is extensively used for forensic purposes. Deoxyribonucleic
      acid (DNA) is the vehicle of generational transference of heritable unit. While
      arching markers for genetic disease professor Alec Jeffreys discovered that
      certain regions of DNA showed variations in the number of tandem repeats known as
      variable number of tandem repeats (VNTRs). Thus DNA fingerprint was named by
      observing the number of repeated sequences which differ from individual to
      individual. The structure of DNA is quite flexible, within the nucleus of each
      cell resides an identical copy of the individual's genetic material, DNA. The
      coding regions of the genomic DNA are known as genes. The DNA fingerprinting in
      forensic science has generated considerable excitement in the criminal justice
      community. DNA fingerprinting can be applied to identify an individual in
      criminal and civil cases. Polymerase chain reaction has revolutionised molecular
      biology it has an ability to amplify (usually fewer than 3000 bp) a particular
      sequence of DNA into million of copies in a very short period. Consequently only
      a very tiny amount of an organism's DNA needs to be available originally. This
      property of polymerase chain reaction has enabled to analyse many forensic
      samples particularly which are degraded. Microsatellite DNA or commonly as short
      tandem repeats are scattered throughout the human genome and occur on an average
      of every 10,000 nucleotides. Microsatellite markers are considered to be the most
      powerful genetic markers. Collection, preservation and handling are the integral
      part of DNA fingerprinting analysis. There are various methods to isolate DNA
      from different biological materials but presently most of the laboratories prefer
      using FTA paper. The age of humans can be estimated by using DNA based on
      telomere shortening.

PMID- 12793632
TI  - AIDS and the medicolegal experts.
AB  - Forensic medicine deals both the living (eg, sexual assaults) as well as dead
      (eg, rape followed by murder) and drug induced death cases. In drug induced death
      or sexual assault cases some of the victims are sufferers of AIDS. HIV
      transmission occurs more in free and unlimited sex. Some points are to be
      remembered as the safety devices while a case of suspected HIV person is examined
      or autopsy is conducted. These points are elaborated in this article. Some legal
      implications are looked into while handling such cases with evidence of AIDS.
      These are also discussed.

PMID- 12793633
TI  - Role of autopsy surgeon in determination of time since death in criminal cases.
AB  - Importance of determination of time since death is very important for the
      investigating agencies, autopsy surgeons and legal authorities in criminal cases
      or when a foul play is suspected behind a death. There are many variabilities and
      probabilities in determination process but the following points are to be read
      and analysed carefully so that it can be easier to ascertain the time since
      death: History and circumstances of death; somatic and molecular signs of death;
      emptying time of stomach and state of digestion of food in the stomach;
      biochemical investigations, etc. The individual points are narrated in a nutshell
      in this article.

PMID- 12793634
TI  - Medicolegal autopsy--what, why and how.
AB  - By the term autopsy means medicolegal autopsy, though there is another one called
      clinical autopsy. The term is synonymous with postmortem examination. Autopsy is
      conducted to ascertain the cause of death, manner of death, time since death, to
      establish the identity of the deceased and so on. As per Mysore Police Manual
      Order No 1380, a civil surgeon or medical officer or other qualified registered
      medical person approved by the State Government is entitled to conduct an
      autopsy. Generally an autopsy is conducted by medical officer concerned on
      requisition from concerned authority in any unexpected, unexplained, unnatural,
      suspicious or sudden death. Autopsy is conducted at the body in its entirety and
      the mutilated body or skeletal remains. After having complied with the medical
      and legal obligations, eventually the medical officer has to furnish his opinion
      based on examination findings and investigation results.

PMID- 12793635
TI  - Role of forensic psychiatrist in updating investigation of crime by mentally ill
      subjects.
AB  - Forensic medicine, the subject in undergraduate medical curriculum is becoming
      more and more important for undergraduate students. Forensic psychiatry is being
      very much felt an important part of crime and criminology and is being thoroughly
      neglected. We cannot ignore the mental status of a person in relation to
      commission of a crime as it is the case in all spheres of life. So updating
      forensic psychiatry in educational programme may play key roles in crime
      investigations. The law can judge the merit of a case on the basis of how far the
      mental abnormality might influence to commit a crime. Investigation of crime has
      to be a compulsorily team work consisting of man of forensic psychiatry or at
      least forensic medicine expert and the other investigating agencies.

PMID- 12793636
TI  - Study of sudden cardiac deaths in young athletes.
AB  - Sudden cardiac deaths in athletes are usually due to underlying cardiovascular
      disease. The final pathway is usually ventricular fibrillation following
      hypertrophic cardiomyopathy and coronary artery anomalies in young persons below
      the age of 30 years. Sudden cardiac death in young is rare but remains as a
      source of concern. A postmortem study was conducted to ascertain the cardiac
      causes of sudden death in persons below the age group 30 years following exercise
      in games or otherwise. Out of 15 cases in autopsy finding, hypertrophic
      cardiomyopathy (n=7) was the commonest cause followed by coronary artery
      anomalies (n=4). Sudden unexpected death is a source of concern and careful
      screening of history and physical examination for potential athletes should
      identify majority of people at risk.

PMID- 12793637
TI  - Dying declaration and doctor.
AB  - A dying declaration is a statement made by a dying person as to the cause of his
      death or as to any circumstances of the transaction that resulted in his death.
      It is an evidence under Section 32 of Indian Evidence Act. Dying declaration can
      be recorded by a magistrate, a doctor, a police officer or even a village head.
      It should be recorded in presence of at least two witnesses. The dying
      declaration may be the basis of conviction if the court is satisfied that the
      dying man had a good opportunity recognising the truth when the declaration was
      made. Doctor's role is very important and complicated in cases when dying
      declaration is needed.

PMID- 12793638
TI  - Live and let live.
AB  - The World AIDS Day was declared by WHO in 1988 and the theme is given for this
      day every year and for the year 2002-03 "Live and let live" is the specific
      theme. According to UNAIDS there are 40-50 million people living with HIV/AIDS
      globally. Stigma and discrimination are major obstacles to effective HIV/AIDS
      prevention. HIV remains unaffected by highly active antiretroviral therapy
      (HAART). The best hope for prevention of HIV rests on the development of a
      globally accessible vaccine. There are many complexities associated with
      conducting AIDS vaccine efficacy trials in the developing world.

PMID- 12793639
TI  - An interesting rare case of sirenomelia.
AB  - In sirenomelia the caudal tissues of the foetus fail to develop because of the
      "stealing" of blood by a vitelline vascular shunt from the distal aorta during
      embryogenesis interfering with foetal development. A 25 years old 2nd gravida
      delivered one full term premature grossly asphyxiated baby at BS Medical College
      on 24-10-1998. The examination of the dead foetus revealed no genitalia, no anal
      nor urethral opening and having a single lower limb with the single thigh and
      rudimentary leg. Skiagram of the foetus corroborated it to be a case of
      syrenomelia.

PMID- 12793640
TI  - Doctor-patient partnership.

PMID- 12793641
TI  - "Prospective evaluation of modified Alvarado score for diagnosis of acute
      appendicitis.

PMID- 12793642
TI  - Local differentiation in Plasmodium falciparum drug resistance genes in Sudan.
AB  - Studies of population genetic structure of parasites can be used to infer which
      parasite genes are under selection. Here, the population structure of 4 genes
      associated with drug resistance of Plasmodium falciparum (the chloroquine
      resistance transporter, pfcrt, dihydrofolate reductase, dhfr, dihydropteroate
      synthase, dhps, and multi-drug resistance, pfmdr-1) were examined in parasite
      populations in 3 villages in eastern Sudan and in an urban area of Khartoum, the
      capital. In order to differentiate the effects of drug selection from neutral
      influences on population structure, parasites were also genotyped for 3
      putatively neutral microsatellite loci (polyalpha, TA81 and pfg377), and for 2
      antigenic loci that are either under balancing selection or neutral, merozoite
      surface protein 1 and 2, (MSP-1 and MSP-2). Cross-sectional surveys were carried
      out during the peak transmission (wet) season and in the ensuing dry season. No
      significant variation in frequencies of MSP-1 and MSP-2 alleles was seen among
      villages in the eastern region and between the villages and Khartoum, nor between
      the wet and dry season. However, the drug resistance genes, pfmdr-1, pfcrt and
      dhfr and to a lesser extent the microsatellite loci showed high FST values when
      comparing villages with Khartoum, indicating strong geographical differentiation
      at these loci. Moreover, variation in frequencies of the drug resistance genes,
      pfmdr-1, pfcrt and dhfr, was observed between the wet and dry season. These
      differences most probably reflect the variation in drug pressure between each
      region, and in drug usage between the wet and dry season in a given region.

PMID- 12793643
TI  - Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine
      sensitivity in Senegal.
AB  - Mutations in pfcrt K76T are associated with chloroquine resistance in Plasmodium
      falciparum. Previous studies of K76T mutations in Senegal reported the
      association of T76 with in vitro-resistant isolates, but this mutation was also
      prevalent in chloroquine-sensitive isolates. This suggests involvement of
      additional genetic loci in modulating chloroquine resistance. Additional pfcrt
      polymorphisms at codons A220S, Q271E, N326S and R371I have been found in
      chloroquine-resistant isolates. We wanted to test if sequential acquisition of
      mutations at these codons leads to in vitro chloroquine resistance. Stepwise
      accumulation of mutations was not detected, rather there was almost complete
      linkage between the pfcrt K76T mutation and polymorphisms in these codons.
      Therefore these additional polymorphisms do not enhance the correlation between
      pfcrt T76 and chloroquine resistance in Senegal. These data suggest that in vitro
      chloroquine resistance requires the genetic background of the pfcrt K76T mutation
      and additional mutations in genetic loci outside the pfcrt gene.

PMID- 12793645
TI  - Modelling the transmission dynamics of Echinococcus granulosus in dogs in rural
      Kazakhstan.
AB  - Cystic echinococcosis, caused by Echinococcus granulosus, is an emerging disease
      in many parts of the world and, in particular, in eastern Europe and the former
      Soviet Union. This paper examines the abundance of infection of E. granulosus in
      the definitive host in southern Kazakhstan. Observed data are fitted to a
      mathematical model in order to decide if the parasite population is partly
      regulated by definitive host immunity and to define parameters in the model. Such
      data would be useful to develop simulation models for the control of this
      disease. Maximum likelihood techniques were used to define the parameters and
      their confidence limits in the model and the negative binomial distribution was
      used to define the error variance in the observed data. The results indicated
      that there were 2 distinct populations of dogs in rural Kazakhstan which had
      significantly different exposures to E. granulosus. Farm dogs, which are closely
      associated with livestock husbandry, particularly sheep rearing, had a relatively
      high mean abundance of 631 parasites per dog and a prevalence rate of
      approximately 23%. The best fit to the model indicated that there was significant
      herd immunity in the dog at this infection pressure. In contrast, village dogs
      which were more likely to be kept as pets had a much lower mean abundance of
      parasites of only 27 parasites per dog and a lower prevalence of 5-8%. With this
      village population of dogs, the best fit indicated negligible herd immunity.

PMID- 12793644
TI  - Cryptosporidium parvum: infectivity and pathogenicity of the 'porcine' genotype.
AB  - Genetic studies have demonstrated profound differences between the 'porcine'
      genotype of Cryptosporidium parvum, versus 'human' and 'bovine' genotypes. The
      study analysed infectivity and pathogenicity of the 'porcine' genotype (CPP-13
      isolate) of C. parvum, and compared the results with published data on the
      'bovine' genotype (CPB-0 isolate). This was investigated in calves and piglets
      from commercial herds. Piglets were mildly affected by the CPP-13 isolate,
      contrary to piglets infected with the CPB-0 isolate, which caused diarrhoea of a
      mean duration of 3.5 days. CPP-13 produced no or very mild clinical signs in
      piglets despite the excretion of high numbers of oocysts. Concomitant infection
      with rotavirus, however, caused a dramatic aggravation of the clinical signs, and
      5 of 6 experimentally infected piglets died. CPP-13 appeared to be adapted to
      porcine hosts as illustrated by the lack of infectivity to 1 experimentally
      inoculated calf, and the absence of clinical signs, the long pre-patent period
      (15 days), and the excretion of very low numbers of oocysts following
      experimental infection of another calf. Thus, in accordance with other molecular
      studies, our results support the genetic evidence for the existence of a new
      species of Cryptosporidium adapted to pigs.

PMID- 12793646
TI  - How does Trypanosoma equiperdum fit into the Trypanozoon group? A cluster
      analysis by RAPD and multiplex-endonuclease genotyping approach.
AB  - The pathogenic trypanosomes Trypanosoma equiperdum, T. evansi as well as T.
      brucei are morphologically identical. In horses, these parasites are considered
      to cause respectively dourine, surra and nagana. Previous molecular attempts to
      differentiate these species were not successful for T. evansi and T. equiperdum;
      only T. b. brucei could be differentiated to a certain extent. In this study we
      analysed 10 T. equiperdum, 8 T. evansi and 4 T. b. brucei using Random Amplified
      Polymorphic DNA (RAPD) and multiplex-endonuclease fingerprinting, a modified AFLP
      technique. The results obtained confirm the homogeneity of the T. evansi group
      tested. The T. b. brucei clustered out in a heterogenous group. For T. equiperdum
      the situation is more complex: 8 out of 10 T. equiperdum clustered together with
      the T. evansi group, while 2 T. equiperdum strains were more related to T. b.
      brucei. Hence, 2 hypotheses can be formulated: (1) only 2 T. equiperdum strains
      are genuine T. equiperdum causing dourine; all other T. equiperdum strains
      actually are T. evansi causing surra or (2) T. equiperdum does not exist at all.
      In that case, the different clinical outcome of horse infections with T. evansi
      or T. b. brucei is primarily related to the host immune response.

PMID- 12793647
TI  - An experimental study of the reproductive success of Echinostoma friedi
      (Trematoda : Echinostomatidae) in the golden hamster.
AB  - Viable eggs produced weekly per infective stage was used as a measure of the
      reproductive success of Echinostoma friedi during the first 12 weeks of infection
      in hamsters. The weekly reproductive success was not constant during the
      experiment in relation to the egg output and the proportion of viable eggs
      produced. The egg release started during week 2 post-inoculation, attaining a
      maximum during week 3. A decline in egg output was observed from week 9. Viable
      eggs were only produced from week 3 post-inoculation and a maximum was attained
      at week 4 of the experiment. A decline in egg viability was observed from week 9.
      Considering together the egg output and the egg viability, the maximum weekly
      reproductive success was obtained during week 4 post-inoculation. The changes in
      the weekly reproductive success were not reflected in variations in worm numbers
      and body sizes during the course of the infection. The humoral immune response of
      golden hamsters during the infection with E. friedi was determined. Increases of
      IgG levels against somatic and excretory/secretory products of E. friedi were
      detected coinciding with the reduction in the reproductive success.

PMID- 12793648
TI  - Description of a tandem repeated DNA sequence of Echinostoma caproni and methods
      for its detection in snail and plankton samples.
AB  - Echinostome larval stages in the snail have a great potential as effective
      competitors for the control of schistosomes and adult worms can cause painful
      intestinal diseases in humans. Ecology and transmission of the larval stages of
      trematodes are poorly understood, especially because their identification in
      field-collected samples by microscopy is difficult. We cloned, sequenced and
      analysed a 192 bp tandem repreated DNA sequence of Echinostoma caproni (EcSau3A),
      an often discussed antagonist of Schistosoma mansoni in Biomphalaria snails. PCR
      primers against this sequence can detect less than 10 fg of E. caproni DNA, 2
      miracidia in snails 1 day p.i., 1 metacercaria in 50 mg snail tissue and 1
      cercaria in 50 mg plankton with high specificity. Methods described in this study
      can support the discovery of fundamental ecological principles on distribution,
      host specificity and epidemiology of E. caproni larvae under field conditions.

PMID- 12793649
TI  - Expressed sequence tag survey of gene expression in the scab mite Psoroptes ovis-
      allergens, proteases and free-radical scavengers.
AB  - Psoroptes ovis, the causative agent of sheep scab, is an important ectoparasitic
      mite infecting sheep, goats and cattle. Infection is characterized by an
      extensive dermatitis, scab formation and intense itching. Initial focal lesions
      spread outwards, coalesce and may extend over the whole body. The host response
      to infestation has all the characteristics of an immediate-type hypersensitivity
      reaction but the mite antigens and allergens which initiate this response are
      almost completely undefined. Here, 507 randomly selected cDNAs derived from a
      mixed population of P. ovis were sequenced and the resultant nucleotide sequences
      subjected to Cluster analysis and Blast searches. This analysis yielded 280
      clusters of which 49 had > 1 sequence with 24 showing significant Blast X
      homology to another protein in the databases. There were 231 sequences which
      appeared on one occasion and 109 of these showed significant Blast X homology to
      other sequences in the databases. This analysis identified homologues of 9
      different types of allergens which have been characterized in other allergic
      conditions such as responses to house dust mites. It also identified a number of
      cysteine proteases which may contribute to lesion development as well as several
      free-radical scavenging enzymes which may protect the mite from host immune
      effector responses.

PMID- 12793650
TI  - Effect of fox, pig, sheep, and poultry bile on the establishment of domestic and
      sylvatic species of Trichinella in rats.
AB  - Most sylvatic species of Trichinella are known to have poor infectivity to rats,
      but in the present study oral administration of bile from other hosts appeared to
      modify this infectivity. A total of 75 rats were inoculated in groups of 25 with
      3 species of Trichinella (T. spiralis, T. nativa, and T. nelsoni) and each group
      of rats was given per os daily doses of bile from pig, sheep, chicken and fox
      respectively (4 x 5 rats). As a control 1 group of 5 rats was given daily doses
      of water. Whereas, the addition of bile did not increase the establishment of T.
      spiralis, fox bile had a significant positive effect on the establishment of
      muscle larvae of T. nativa and T. nelsoni. Addition of bile to cultures of the
      same Trichinella species had an overall negative effect on the in vitro survival
      of larvae. The present observation that carnivore bile favours the establishment
      of sylvatic Trichinella may explain why carnivores are equally receptive to all
      Trichinella species.

PMID- 12793651
TI  - Genetic variation within and among infrapopulations of the marine digenetic
      trematode Lecithochirium fusiforme.
AB  - Allozyme markers were used to study genetic variation in Lecithochirium fusiforme
      within a natural population of Conger conger. Six of 16 enzyme-coding loci
      studied were found to be polymorphic. These loci were surveyed in 12
      infrapopulations of adult flukes. High levels of genetic variation were detected
      (P = 0.375); Ho = 0.048; He = 0.085). However, the population did not conform to
      Hardy-Weinberg expectations, as it showed a significant deficit of heterozygotes.
      L. fusiforme also exhibited low differentiation between infrapopulations (FST =
      0.064). Despite significant linkage disequilibrium at Pgm-1 and Pgm-2 (P < 0.05),
      mating system does not appear to be the principal reason for the deficit of
      heterozygotes detected, because some polymorphic loci were in Hardy-Weinberg
      equilibrium. Association between FIS and FST statistics suggests the existence of
      the Wahlund effect. However, all infrapopulations showed a strong deficit of
      heterozygotes for most polymorphic loci (FIS = 0.409). Detection of significant
      genetic differentiation among temporal samples and the existence of paratenic
      hosts in the life-cycle suggests the Wahlund effect, caused by the mixture of
      genetically distinct temporal samples in the infrapopulations. Occasional
      temporal gene flow also might explain the high estimated genetic polymorphism.

PMID- 12793652
TI  - Parasite specialization from a phylogenetic perspective: a new index of host
      specificity.
AB  - The host specificity of a parasite is not merely a function of how many host
      species it can exploit, but also of how closely related these host species are to
      each other. Here, a new index of host specificity is proposed, one that takes
      into account the average taxonomic or phylogenetic distance between pairs of host
      species used by a parasite. The index is derived from measures of taxonomic
      distinctness used in biodiversity studies. It is easy to compute and interpret,
      ranging from a minimum value of 1 when all host species are members of the same
      genus, to a maximum of 5, when all host species belong to different classes. The
      variance of this measure can also be computed, and provides additional
      information on the taxonomic or phylogenetic structure of the host assemblage.
      Using data on helminth parasites of Canadian freshwater fishes, we show that the
      new index, unlike the mere number of known host species, is independent of study
      effort i.e. the number of published records of a parasite. Although the index and
      the number of known hosts are not entirely independent statistically, each
      captures a different aspect of host specificity. For instance, although
      acanthocephalans infect significantly more host species than trematodes, cestodes
      or nematodes, there is no difference in the average index value among these 4
      helminth taxa, suggesting that the average taxonomic distances between the host
      species of a parasite do not vary among these higher taxa. We recommend the use
      of our new index in future comparative studies of host specificity, in particular
      when the focus is on the evolutionary history of parasites and of their past
      colonizations of host lineages.

PMID- 12793653
TI  - Patterns of the tapeworm Raillietina trapezoides infection in the fat sand rat
      Psammomys obesus in Tunisia: season, climatic conditions, host age and crowding
      effects.
AB  - The tapeworm Raillietina trapezoides was studied in a Tunisian population of the
      fat sand rat Psammomys obesus. Seasonal changes in the abundance of parasite and
      host were monitored in a longitudinal field survey lasting 20 months. In total
      582 intestinal samples were collected during 10 trapping sessions between May
      1995 and January 1997 and examined. The impact of abiotic and biotic factors on
      the prevalence and parasite burden were explored, using generalized linear
      models. R. trapezoides showed a seasonal pattern with most transmission occurring
      in summer and autumn. In August-September when the rodents were at low density
      and most adult (90-100%) were infected. In winter, infections with R. trapezoides
      were highly prevalent in the cohort of adults only. The worm burden by number was
      also high in late summer and autumn. Prevalence and parasite burden by number or
      by biomass were highly age dependent. Season and age act in synergy so that the
      rodents were highly infected in late summer and autumn. Unusually dry conditions
      in winter seemed to increase prevalence and to reduce the number of worms. There
      was no difference between males and females in prevalence or parasite burden (by
      number or by biomass). Prevalence was not correlated with the relative density of
      the hosts whereas parasite burden depended upon their densities. The more
      numerous the worms were, the smaller they were individually, reflecting a
      crowding effect. The possibility of an immune response regulating P. obesus is
      discussed, in regard to the very high natural prevalence and the variation in
      worm burden, and compared with other parasite-host systems.

PMID- 12793654
TI  - Genetic differentiation in populations of the cestode Bothriocephalus
      acheilognathi (Cestoda, Pseudophyllidea) as revealed by eight microsatellite
      markers.
AB  - The genetic structure of populations of the fish cestode, Bothriocephalus
      acheilognathi collected from Bailianhe Reservoir (BLH), Changshou (CSH) and
      Liangzi (LZH) Lakes was investigated by using 8 microsatellite loci. A total of
      108 adult worms were genotyped at each of the 8 loci. For the 3 populations, the
      mean number of alleles per locus ranged from 2.38 to 5.5, and the mean expected
      heterozygosity ranged from 0.432 to 0.559. The average polymorphic information
      content (PIC) was from 0.384 to 0.492. The significant Fis values indicated non
      random mating within LZH and BLH populations. On the other hand, when samples
      were further classified into subpopulations at the level of host fish species, no
      or little heterozygote deficiency was detected at most loci, showing that cross
      fertilization, predominantly, but not exclusively, must have occurred within the
      subpopulations. Microsatellite markers also revealed an unexpected high level of
      genetic differentiation, as measured by R(st) and N(m) values or by delta(u)2
      genetic distance among subpopulations from different hosts. Factors influencing
      the population genetic structure and the parasite host specificity are discussed.

PMID- 12793655
TI  - Evaluating integrated urban water systems alternatives for Brisbane, Australia.
AB  - The Brazil Development Study investigates the feasibility of alternative
      approaches to providing sustainable water services to a 226 ha mixed residential
      and industrial greenfield development within the city of Brisbane, Australia. The
      alternatives include techniques such a the use of rainwater tanks, water use
      efficiency, a local wastewater treatment plant for recycling of reclaimed water
      and composting toilets amongst others. This paper evaluates a series of urban
      development scenarios against the objectives of the study. The insights gained
      into the drivers for cost and environmental impact for this particular site are
      discussed as well as a number of issues of concern and challenges to Council and
      the community.

PMID- 12793656
TI  - A conceptual framework for the sustainable management of wastewater in Harare,
      Zimbabwe.
AB  - The aim of this study was to formulate an integrated wastewater management model
      for Harare, Zimbabwe, based on current thinking. This implies that wastewater is
      treated/disposed of as close to the source of generation as possible. Resource
      recovery and reuse in a local thriving urban agriculture are integrated into this
      model. Intervention strategies were considered for controlling water, nitrogen
      and phosphorus flows to the lake. In the formulation of strategies, Harare was
      divided into five major operational areas of high-, medium-, and low-density
      residential areas, and also commercial and industrial areas. Specific options
      were then considered to suit landuse, development constraints and socio-economic
      status for each area, within the overall criteria of limiting nutrient inflows
      into the downstream Lake Chivero. Flexible and differential solutions were
      developed in relation to built environment, population density, composition of
      users, ownership, future environmental demands, and technical, environmental,
      hygienic, social and organisational factors. Options considered include source
      control by the users (residents, industries, etc.), using various strategies like
      implementation of toilets with source separation, and natural methods of
      wastewater treatment. Other possible strategies are invoking better behaviour
      through fees and information, incentives for cleaner production, and user
      responsibility through education, legislative changes and stricter controls over
      industry.

PMID- 12793657
TI  - Integrated urban water planning: big picture planning is good for the wallet and
      the environment.
AB  - The demands on governments and local authorities are changing in response to
      community expectations for environmentally sustainable outcomes. To reverse
      declining water quality in rivers and ensure sustainable use in the 21st century,
      the State Government in New South Wales has introduced a package of Water
      Reforms. The introduction of integrated water, sewerage and drainage planning is
      one of the Water Reform initiatives. Traditionally, government and local
      authorities have managed their water supply, sewerage and stormwater drainage
      systems as separate entities. Integrated urban water planning is a structured
      planning process to evaluate concurrently the opportunities to improve the
      management of water, sewerage and drainage services within an urban area in ways
      which are consistent with broader catchment and river management objectives. The
      New South Wales Department of Land & Water Conservation (DLWC) has developed an
      integrated urban water planning process through a number of recent pilot studies.
      The process links urban water management objectives to overall catchment and
      river management objectives. DLWC is currently developing a set of guidelines for
      integrated urban water plans. DLWC has developed the Integrated Urban Water
      Planning methodology through three pilot studies in the New South Wales towns of
      Finley, Goulburn and Bombala. The pilot studies have shown that an integrated
      approach to water, sewerage and stormwater planning can identify opportunities
      that are not apparent when separate strategies are developed for each service.
      The result is better-integrated, more sustainable solutions, and substantial cost
      savings for local communities.

PMID- 12793658
TI  - Sustainable water cycle design for urban areas.
AB  - This paper presents the argument that the environmental, social and economic
      benefits of decentralised systems are such that they should present a serious
      alternative to centralised systems in existing and future planned urban
      developments. It will be shown that the combination of technical, social and
      regulatory factors that influenced the popularity of centralised systems has
      altered, and that decentralised systems should now be considered as well. The
      environmental, social and economic advantages and disadvantages of several
      sustainable watercycle case studies are examined and compared with centralised
      systems. The studies examined will go from large scale down to designs suitable
      for typical residential houses on standard urban blocks.

PMID- 12793659
TI  - Sustainability concept for a newly built urban area in Malmo, Sweden.
AB  - National goals regarding sustainable development from the Swedish government were
      decisive in the planning process when the newly built city district Western
      Harbour was established in the city of Malmo, Sweden. A systems analysis was used
      as a tool for evaluating different collection and treatment systems. This type of
      analysis does not include more subjective factors such as acceptance of organic
      fertilizers based on human waste and user acceptance of collection schemes. These
      aspects, however, will often determine the success of a technical solution. When
      the system for collection and treatment of old organic waste and wastewater was
      designed, both subjective and objective factors were considered. This meant that
      a centralised solution for wastewater treatment was selected. In order to
      facilitate a more sustainable solution for sludge management a treatment process
      with recovery of phosphorus will have to be introduced. Organic waste is sorted
      out and treated in an anaerobic digestion process. Source sorting of solid
      organic waste has been difficult to implement in Sweden due to inadequate sorting
      discipline. As a consequence two relatively new systems are tested in the area. A
      comprehensive evaluation will be carried out during a period of two years.

PMID- 12793660
TI  - Aral Sea and sustainable development.
AB  - Until 1960 the Aral Sea was considered the 4th largest lake in the world by
      surface area. The Aral Sea has two main inflows--the Amudarya and Syrdarya rivers
      with about 30 tributaries. From early 1960s because of extensive water use-
      unreturned withdrawal of water for irrigation and consequent drying up of many
      tributaries before reaching the main rivers--the water level in the Aral Sea
      began falling very rapidly. In 1965 the Aral Sea received about 56 cubic km of
      fresh water yearly, but this number fell to zero by the early 1980s. By 1990 the
      level of the Aral Sea water fell by more than 17 m, the volume of water decreased
      by 75%, the salinity of seawater increased up to 30 g/l, and the surface area of
      the sea reduced from 66,400 sq. km to 31,500 sq. km. The ecological situation in
      Aral Sea zone has became very dramatic. It has led to the changing of climate in
      the region, irrigated soils becoming deserts, deterioration of underground and
      surface water quality, reducing of available water for domestic and agricultural
      needs, loss of Aral Sea fishing and transportation importance, numerous other
      problems and finally put the health of present and future generations under
      threat. This situation not only does not promote further development of the
      economy of the region, but has also caused damage with irreparable negative
      consequences. The fact is that the basis of the regional economy is fishing and
      other associated businesses. Since Uzbekistan is most agricultural country its
      economy has serious complications. In order to prevent further deepening of this
      catastrophe and to improve the present situation in this area the Government of
      the Republic of Uzbekistan has developed a series of measures: in particular it
      developed efficient water use schemes, changing the cotton situation (that during
      the Soviet period was grown as monoculture) by planting less water-consuming
      varieties, reviewing using of fertilizers in agriculture etc. The Aral Sea
      drought became an international disaster. World Bank, UNESCO, BMBF and others
      attacked the problem to protect the Aral Sea.

PMID- 12793661
TI  - Hydraulics of sub-superficial flow constructed wetlands in semi arid climate
      conditions.
AB  - This paper reports the evaluation of the hydraulics of two constructed wetland
      (cw(s)) plants located in Apulia (the South Eastern Italy region characterized by
      semi arid climate conditions). These fields were planted with Phragmites
      australis hydrophytes and are supplied with local secondary wastewater municipal
      treatment plant effluent. Each plant--Kickuth Root-Zone method based--covers an
      area of approx. 2,000 m2. The evapotranspiration phenomenon has been evaluated
      within perforated tubes fixed to the field bottom and very high values--up to 40
      mm/d--were found. Hydraulic conductivity has been evaluated by in situ
      measurements at different field points. Hydraulic gradients and the piezometric
      curve within the field are also reported.

PMID- 12793662
TI  - Water recycling: a major new initiative for Melbourne--crucial for a sustainable
      future.
AB  - Melbourne Water has adopted a challenging target of recycling 20 per cent of
      treated effluent from Melbourne's two major sewerage treatment plants by 2010.
      This target was adopted in response to key drivers for water recycling in the
      Melbourne region such as: strong support for conserving water resources and
      protecting marine environments; acknowledgment of recycled water as a valuable
      resource; greater emphasis on environmental issues and sustainable management
      principles; and opportunities to increase demand for recycled water through
      effective planning mechanisms. Issues that must be effectively addressed to meet
      the target include: managing public perceptions of recycled water; health and
      environmental concerns; lack of consensus among government agencies; high up
      front costs of infrastructure; and prices of other sources of water supply not
      currently true costed. Melbourne Water has identified the following factors as
      critical in determining the success of recycling strategy: ability to demonstrate
      that water recycling will be important in terms of long term water cycle
      management; effective stakeholder consultation; gaining government support;
      establishing long-term, guaranteed markets for recycled water; implementing well
      planned, large scale recycling schemes; ability to provide a product that meets
      customer needs; regulatory approval; and implementation of a system that is
      economically viable. Water recycling initiatives are being investigated on
      household, local and regional levels. Over 10 proposals that will contribute to
      the 20 per cent recycled water target from the regional treatment plants are
      under various stages of development. Melbourne Water's commitment to recycling
      within a total water cycle management context is a vital component of this major
      new initiative for Melbourne and is crucial for a sustainable future.

PMID- 12793663
TI  - Wastewater services for small communities.
AB  - Connection to centralised regional sewage systems has been too expensive for
      small-dispersed communities, and these townships have traditionally been serviced
      by on-site septic tank systems. The conventional on-site system in Australia has
      consisted of an anaerobic holding tank followed by adsorption trenches. This
      technique relies heavily on the uptake of nutrients by plants for effective
      removal of nitrogen and phosphorus from the effluent, and is very seasonal in its
      efficiency. Hence, as these small communities have grown in size, the
      environmental effects of the septic tank discharges have become a problem. In
      locations throughout Australia, such as rural Victoria and along the Hawkesbury
      Nepean River, septic tanks as being replaced with the transport of sewage to
      regional treatment plants. For some isolated communities, this can mean spending
      20,000 dollars-40,000 dollars/household, as opposed to more common connection
      prices of 7,000 dollars/household. This paper explores some alternative options
      that might be suitable for these small communities, and attempts to identify
      solutions that provide acceptable environmental outcomes at lower cost. The types
      of alternative systems that are assessed in the paper include local treatment
      systems, separate blackwater and greywater collection and treatment systems both
      with and without non-potable water recycling, a small township scale treatment
      plant compared to either existing septic tank systems or pumping to a remote
      regional treatment facility. The work demonstrated the benefits of a scenario
      analysis approach for the assessment of a range of alternative systems. It
      demonstrated that some of the alternatives systems can achieve better than 90%
      reductions in the discharge of nutrients to the environment at significantly
      lower cost than removing the wastewater to a remote regional treatment plant.
      These concepts allow wastewater to be retained within a community allowing for
      local reuse of treated effluent.

PMID- 12793664
TI  - Sustainable urban development in Brisbane City--the Holy Grail?
AB  - Impacts from urban stormwater runoff on receiving environments have been well
      documented, particularly through specific regional scientific studies. Using
      various local government planning and management elements, urban developments in
      Brisbane City are now able to address stormwater management in an increasingly
      holistic context. One key initiative includes facilitating Water Sensitive Urban
      Design (WSUD) components within an Integrated Water Management Strategy that
      looks at policy formation, planning strategies, design option, community
      marketing and acceptance, maintenance programs and finally evaluation of various
      WSUD approaches. These can include the use of Natural Channel Designs, grassed
      swales, bio-filtration systems, porous pavements and roofwater tanks in several
      economic combinations. By linking with the Cooperative Research Centre for
      Catchment Hydrology, Brisbane City Council has influenced the design of WSUD
      planning tools and benefited the city with academic inputs into extensive
      evaluation programs. As well, it has also contributed to the Cooperative Research
      Centre's research outcomes. These evaluation programs are increasingly providing
      better understanding of various stormwater quality best management practices
      throughout Australia. As part of the overall implementation process, active
      involvement by a range of stakeholders has been crucial. These stakeholders have
      included internal planning, development assessment and design staff, external
      consultants, developers, and other local and state government agencies. The
      latter two groups are assisting in the important task of "regionalisation" of
      Brisbane City Council's policies and guidelines. Implementation of WSUD
      initiatives and stormwater re-use strategies under Council's new "Integrated
      Water Management" agenda are showing some excellent results, suggesting that
      sustainable urban development is no longer like the search for the Holy Grail.

PMID- 12793665
TI  - Integrated water resources management in the Ruhr River Basin, Germany.
AB  - The Ruhr, with an average flow of 80.5 m3/s at its mouth, is a comparatively
      small tributary to the Rhine River that has to perform an important task: to
      secure the water supply of more than 5 million people and of the industry in the
      densely populated region north of the river. The complex water management system
      and network applied by the Ruhrverband in the natural Ruhr River Basin has been
      developed step by step, over decades since 1913. And from the beginning, its
      major goal has been to achieve optimal conditions for the people living in the
      region. For this purpose, a functional water supply and wastewater disposal
      infrastructure has been built up. The development of these structures required
      and still requires multi-dimensional planning and performance. Since the river
      serves as receiving water and at the same time as a source of drinking water, the
      above-standard efforts of Ruhrverband for cleaner water also help to conserve
      nature and wildlife. Ruhrverband has summed up its environmental awareness in the
      slogan: "For the people and for the environment". This basic water philosophy,
      successfully applied to the Ruhr for more than 80 years, will be continued in
      accordance with the new European Water Framework Directive, enacted in 2000,
      which demands integrated water resources management in natural river basins, by
      including the good ecological status of surface waterbodies as an additional
      goal.

PMID- 12793666
TI  - Integrated water cycle planning for towns in New South Wales, Australia.
AB  - Integration means different things to different people and as a consequence
      appears to only partially deliver on promised outcomes. For effective integrated
      water cycle management these outcomes should include improved water use
      efficiency, less waste, environmental sustainability, and provide secure and
      reliable supply to meet social and economic needs. The objective of integration
      is the management and combination of all these outcomes as part of a whole, so as
      to provide better outcomes than would be expected by managing the parts
      independently. Integration is also a consequence of the Water Reforms embarked on
      by the NSW State Government in 1995. The key goals of the reforms are clean and
      healthy rivers and groundwaters, and the establishment of more secure water
      entitlements for users. They are also essential for meeting the Council of
      Australian Government (COAG) water management strategies. The policies and
      guidelines that formed the NSW Water Reforms were the basis of the Water
      Management Act 2000 (NSW) (WMA) which is the legislative framework for water
      management in NSW. The NSW Department of Land and Water Conservation has
      developed an approach to integrated water cycle management for rural centres in
      NSW based on a catchment and policy context. This approach includes consideration
      of catchment wide needs and issues, environmental sustainability, government
      policy and community objectives in the development of an integrated water cycle
      plan. The approach provides for a transparent assessment of priorities and how to
      deal with them, and while specific to urban centres, could easily be expanded for
      use in the management of the whole of the catchment water cycle. Integration of
      the water cycle is expected to offer benefits to the local environment, community
      and economy. For instance, any unused proportion of an urban centre's water
      entitlement, or an offset against this entitlement created through returned flows
      (such as via good quality sewage effluent discharge to a river), can provide a
      surplus which is available to be traded on an annual basis. Further, improved
      demand management within an urban centre can be expected to result in a reduction
      in abstraction against the licence entitlement. This may result in the increased
      availability of in-stream water for environmental or other purposes and is
      expected to increase the economic value of returned water. Improved water use
      efficiencies are also expected to result in reduced capital works (and their
      associated costs) as the efficiency of service delivery and resource use
      improves. In this paper an example of the application of this process is provided
      and the outcomes discussed.

PMID- 12793667
TI  - Bacterial source tracking and shellfish contamination in a coastal catchment.
AB  - Introduced pathogens from faecal material can make their way into the aquatic
      environment from a number of catchment sources. These sources typically include
      sewage outfalls, seepage from septic tanks, and urban and agricultural runoff.
      Shellfish as filter feeders are particularly susceptible to contamination in
      faecally contaminated waters and a range of microbiological indicators have been
      developed to assess the levels of contamination and likely risks to public health
      (Hackney and Pierson, 1994). This paper outlines the application of bacterial
      source tracking (BST) in a shellfish growing area in part of the Port Stephens
      estuary along the NSW north coast. The approach is based on the premise that
      bacterial isolates from different faecal sources will have significantly
      different resistance patterns to the battery of antibiotics and concentrations
      tested. Faecal streptococci (FS) were isolated from several possible faecal
      sources: beef and dairy cattle, chickens and humans. The resistance patterns of
      these isolates to four different concentrations of four antibiotics were compared
      to those of FS isolates obtained from samples collected upstream and in the
      vicinity of the oyster leases. Discriminant analysis was performed using the
      patterns from the known source isolates and the rate of correct classification
      was determined for each source. The predictive function of discriminant analysis
      was then used to determine the most probable source of each of the unknown
      isolates from Tilligerry Creek, the drainage channels to the estuary, and the
      shellfish leases. Preliminary results are presented here and suggest that there
      is no single significant source of faecal contamination, rather there are
      contributions from a range of sources. The findings may have implications for the
      ways in which land use activities and catchments are managed in similar estuarine
      locations with a shellfish industry.

PMID- 12793668
TI  - Climate change and reliability of urban water supply.
AB  - This paper describes a probability-based method for assessing the potential
      impact of climate change on urban water supply systems. Specifically, the
      assessment method uses probability distributions to place a confidence level on
      the plausible values of response variables. The Benalla water supply system has
      been used to demonstrate applicability of the proposed assessment method. For the
      application, impact of the 2030 climate change scenarios on streamflows and
      system yield has been examined. The preliminary results have demonstrated that
      the proposed assessment method can provide valuable insights into the impact of
      climate change on water supply systems, allowing it to be incorporated into
      planning decisions.

PMID- 12793669
TI  - Integrated environmental assessment of tertiary and residuals treatment--LCA in
      the wastewater industry.
AB  - In the wastewater industry, decision-makers lack access to an environmental tool
      that can assist in further informing the non-financial analysis of a system. Such
      a tool should incorporate impacts beyond the effluent quality and look at the
      supporting processes of a plant as well as plant specific operations. Life Cycle
      Assessment can provide the means to fill a gap in pertinent information towards
      more sustainable decision-making. The project "Best Practice LCA in the
      Wastewater Industry" is commissioned by the CRC for Waste Management and
      Pollution Control at UNSW with representatives from Sydney Water Corporation
      (SWC), NSW Department of Land and Water Conservation and the NSW Department of
      Public Works. Two case studies were researched to provide a post-implementation
      review of changes in wastewater. Case study 1: The conversion from chlorine gas
      to hypochlorite and UV disinfection has been completed for several inland
      wastewater plants at SWC. A review of operational data for each of the options
      has been incorporated into an LCA of each technology. Under efficient dosing
      conditions, disinfection with the hypochlorite system has the minimum
      environmental impact. Case study 2 deals with the conversion from anaerobic to
      aerobic digestion. Aerobic digestion minimises release of nutrients into a
      sidestream to be further treated in the plant. However conversion results in more
      biosolids production and higher electricity requirements. This study includes a
      consideration of the environmental impacts of biosolids production and
      application. On the basis of the extended boundary including consideration of
      reflux composition, energy requirements and biosolids quality to potentially
      offset fertiliser production, anaerobic digestion performs best in 6 out of 9
      impact categories. These results suggest that environmental LCA has a role in
      informing decision-making on unit process and treatment train selection by
      quantifying aspects on non-financial criteria. Also, improvement potentials are
      foreshadowed but not detailed.

PMID- 12793670
TI  - The effects of humic substances on the intake of micro-organic pollutants into
      the aquatic biota.
AB  - Humic substances, naturally occurring highly polymerized organic compounds, exist
      widely in the water and soil environments. It has been known that the humic
      substances affect the fate of micro-organic pollutants (e.g. intake,
      accumulation, movement, degradation, toxicity, etc.). Of these, the effect of
      humic substances on the intake into biota (i.e. living cell) is one of the most
      important. In this research, the effects of co-existing humic substances on the
      intake of micro-organic pollutants into aquatic biota were experimentally
      evaluated. The humic acid filtrate using a 3,000 Da ultra-filtration membrane was
      used. Two PAHs (i.e. pyrene and phenanthrene) were used as micro-organic
      pollutants. Liposome for simulating living cell membrane was synthesized in the
      laboratory, and used for investigating the intake of micro-organic pollutants
      into aquatic biota precisely. The batch experiment results (PAHs onto humic acid,
      humic acid into liposome, and PAHs into liposome (K(lipw))) led to the fact that
      the sorption of PAHs into liposome is suppressed apparently by binding with humic
      acid in the aqueous phase. This suggests that the accumulation and/or toxicity of
      micro-organic pollutants is retarded by humic substances in the actual aqueous
      environment. Moreover, the experimental results indicated that the sorption into
      liposome (i.e. liposome/water partition coefficient (K(lipw))) could be a better
      parameter for estimating the intake of micro-organic pollutants into aquatic
      biota than n-octanol/water partition coefficient (K(ow)) in the aqueous
      environment.

PMID- 12793671
TI  - Periphyton collectors as a tool to measure environmental performance of ocean
      outlets.
AB  - Brown and Root has participated in extensive investigations of the effects of the
      discharges from Perth's Ocean Outlets, as part of the Perth Long-Term Ocean
      Outlet Monitoring (PLOOM) Programme (1995 to 2001). The major environmental
      concern with these discharges is the potential for nutrients in the wastewater to
      stimulate excess primary production in the sea. PLOOM, and its predecessor, the
      Perth Coastal Waters Study, have been instrumental in developing parameters for
      the measurement of the performance of Perth's ocean outlets. These parameters are
      currently being integrated in the development of Environmental Quality Criteria
      (EQC) for the Perth region. EQC play an important role in the management
      framework by providing the quantitative benchmarks for measuring success in
      achieving the environmental quality objectives. PLOOM has monitored a range of
      environmental parameters in the Perth Metropolitan area, including water quality,
      nutrient levels, water circulation and plume dilution, levels of metals and
      pesticides present in the marine environment, and the environmental health of
      benthic communities, in particular of temperate reef systems. During the PLOOM
      studies, a valuable tool was being developed to monitor outlet performance.
      Artificial reef structures ("periphyton collectors") were placed in the plume
      trajectory. Here, periphyton is defined as: the microalgae (diatoms and
      microscopic filamentous forms), algal propagules, bacteria, microfauna and
      particulate material that are found in a mucous-like layer commonly coating
      seagrass leaves, and that initially colonise artificial surfaces. The advantage
      of periphyton collectors is that these largely remove the effects of natural
      variability, can be placed at any depth and distance from a potential nutrient
      source, provide an easy, cost effective measure of environmental impact,
      integrated over an extended period (one month), and produce tangible results
      which can be interpreted by the wider community, as well as legislative
      authorities and by outlet managers. In addition, outlet performance can be
      measured by means of these tools, and tested against accepted environmental
      criteria. Between 1995-2001, periphyton collectors, consisting of 15 x 15 cm PVC
      plates attached to moorings at fixed depths (2, 4 and 8 m), were deployed for one
      month during spring, summer and autumn, at increasing distance from the source
      (250 and 500 m distance to the north, east, west, and south, and at 1,000, 2,000,
      4,000 m to the north and south only). After retrieval, the collectors were
      analysed for total biomass (g AFDW m(-2)), calcium carbonate content (% AFDW) and
      chlorophyll levels (chlorophyll a m(-2)). The results confirmed the predictions
      made by hydrodynamic modelling (e.g. Zic and Gondinoudis, 2002) and are in
      accordance with measured nutrient and chlorophyll a levels around the outlets,
      and demonstrated that the zone of influence was strongly determined by the
      prevailing currents (to the north), and largely restricted to surface layers (2-4
      m depth). Both biomass and chlorophyll content proved reliable parameters, which
      have the potential to be used as Environmental Quality Criteria (EQC's) for the
      management of Perth's coastal waters. These EQC's were developed in collaboration
      with legislative authorities, as part of draft criteria, in accordance with
      national guidelines: ANZECC/ARMCANZ (2000) Australian and New Zealand Guidelines
      for Fresh and Marine Water Quality.

PMID- 12793672
TI  - Ordination and classification of macroinvertebrates and environmental data of a
      stream in Turkey.
AB  - Macroinvertebrate communities and environmental variables were assessed in an
      Ankara Stream receiving high organic and industrial wastes. Environmental data
      were used to explain biological variation using multivariate techniques provided
      by the program CANOCO. The ordination method CCA (Canonical Correspondence
      Analysis) was applied to evaluate the relationships between environmental
      variables and distribution of macroinvertebrate genera. Data sets were classified
      by TWINSPAN (Two Way Indicator Species Analysis). In this investigation,
      macroinvertebrate communities have been shown by CCA ordination to be related to
      TOM (total organic matter), ammonia, cadmium, pH, lead, dissolved oxygen,
      conductivity (EC), phosphate, boron, nitrite and hardness, with TOM, ammonia,
      cadmium and pH emerging as the most significant environmental variables. Epeorus
      was a TWINSPAN indicator for the slightly polluted upstream site 1. Physa was a
      TWINSPAN indicator for the polluted downstream sites.

PMID- 12793673
TI  - River basin management, described for the example of the Emschergenossenschaft.
AB  - Considerable problems concerning drainage capacity made it necessary, at the
      beginning of the 20th Century, to make a joint public-private effort, because the
      existence of the Ruhr Area as an industrial location was endangered. By Prussian
      law a co-operative was established for wastewater and drainage-management of the
      entire Emscher river system. In the past the Emscher Association and the later
      founded Lippe Association have proved to be the best instrument to cope with the
      wastewater problems of a densely-populated industrial area. In recent time, the
      Emscher area is undergoing fundamental structural changes. To increase its
      attractiveness increased efforts are needed for a modernisation of the wastewater
      transport and treatment system. To deal with the various and complex tasks to
      reshape the Emscher system, the joint association again provides a highly
      efficient and competent instrument.

PMID- 12793674
TI  - Management strategies for a eutrophic water supply reservoir--San Roque,
      Argentina.
AB  - Possible management strategies to improve water quality in a eutrophic water
      supply reservoir in Argentina were evaluated using the one-dimensional coupled
      hydrodynamics and water quality model DYRESM-CAEDYM. The model was used to
      determine the effects of several different artificial destratification system
      designs (including both bubble plume diffusers and surface impellers with draft
      tubes, both separately and in combination), on the biomass of the potentially
      toxic cyanobacteria Microcystia aeruginosa. The best results were found by using
      a combination of a deep and shallow diffuser, to break down the seasonal
      thermocline and therefore limit sediment nutrient release and anoxia, and to
      enhance vertical mixing in the surface mixed layer, respectively.

PMID- 12793675
TI  - Use of active barriers to reduce eutrophication problems in urban lakes.
AB  - Excessive concentration of phosphorus is one of the main causes of algal blooms
      and eutrophic conditions in lakes. In many urban lakes, it appears that a large
      proportion of the phosphorus in the water column comes from the sediments,
      particularly when these are anaerobic. Sub-aqueous capping is a relatively new
      method that has become an attractive option for isolating contaminated sediments
      from the environment, thus preventing or delaying the release of contaminants
      into surface waters. Active barrier materials (i.e. capping layers that consist
      of one or more reactive components) are gaining increasing attention for their
      greater efficiency in inactivating contaminants held in sediment layers. This
      paper reports laboratory bioreactor experiments to test the effectiveness of
      three forms of calcium carbonate (CaCO3) in reducing the release of phosphorus
      from anaerobic sediment from Lake Carramar, a small urban lake in Melbourne. Two
      of the CaCO3 active barrier materials tested proved to be quite effective, the
      most effective materials being the fine particle size, precipitated forms of
      CaCO3. Over the 20-day experimental period, a 2% layer of the German material
      SoCal reduced the amount of phosphorus released by almost 100 times over that
      occurring with no barrier. The Australian product ESCal, while not as effective
      as the SoCal, still reduced the phosphorus released by around 15 times that with
      no barrier. A finely ground Lilydale limestone was essentially ineffective in
      reducing phosphorus release from the sediments. A preliminary cost-benefit
      analysis suggests that SoCal is unlikely to be attractive for use in Australia,
      given the estimated application cost of around 3,800 dollars per tonne. However,
      although the ESCal is slightly less effective in retaining phosphorus, its
      potential application cost estimated at 2,000 dollars per tonne, makes it an
      attractive option. On the basis of these most promising preliminary results, we
      intend to further test the use of the ESCal. Further investigations will include:
      longer term laboratory studies using ESCal, optimisation of the barrier layer and
      methods for applying this material, mesocosms and full lake studies, and risk
      assessment studies to ensure there are no adverse ecological effects from its
      use.

PMID- 12793676
TI  - Potential impacts of global warming on water resources in southern California.
AB  - Global warming will have a significant impact on water resources within the 20 to
      90-year planning period of many water projects. Arid and semi-arid regions such
      as Southern California are especially vulnerable to anticipated negative impacts
      of global warming on water resources. Long-range water facility planning must
      consider global climate change in the recommended mix of new facilities needed to
      meet future water requirements. The generally accepted impacts of global warming
      include temperature, rising sea levels, more frequent and severe floods and
      droughts, and a shift from snowfall to rain. Precipitation changes are more
      difficult to predict. For Southern California, these impacts will be especially
      severe on surface water supplies. Additionally, rising sea levels will exacerbate
      salt-water intrusion into freshwater and impact the quality of surface water
      supplies. Integrated water resources planning is emerging as a tool to develop
      water supplies and demand management strategies that are less vulnerable to the
      impacts of global warming. These tools include water conservation, conjunctive
      use of surface and groundwater and desalination of brackish water and possibly
      seawater. Additionally, planning for future water needs should include explicit
      consideration of the potential range of global warming impacts through techniques
      such as scenario planning.

PMID- 12793677
TI  - Wastewater quality improvement through storage: a case study in Sicily.
AB  - This paper presents the results of a research aiming at evaluating the effects of
      storage on wastewater characteristics. Wastewater discharged from the Caltagirone
      (Eastern Sicily) plant after secondary treatment was stored in an earth reservoir
      with a capacity of about 25,000 m3 and a depth of 5 m. Wastewater inflow in the
      reservoir was continuous throughout the experimental activities, while discharge
      was discontinuous, depending on irrigation demand. Removal efficiency resulted
      highly influenced by the operation regime of the reservoir and by influent
      wastewater characteristics. BOD5 and COD removal efficiency was above 50%.
      Removal efficiency of faecal coliforms, faecal streptococci and Escherichia coli
      was between 2 and 5 log units. Single and multiple regressions were tested to
      determine the reservoir design characteristics and operation parameters that most
      significantly affected water quality changes.

PMID- 12793678
TI  - Baseline hydraulic performance of the Heathrow constructed wetlands subsurface
      flow system.
AB  - A constructed wetland treatment system has been commissioned by BAA (formerly the
      British Airports Authority) in order to attenuate airfield runoff contaminated
      with de-icant and other potentially polluting materials from Heathrow Airport.
      Airfield runoff containing de-icants has the potential to impose significant
      oxygen demands on water bodies. The site consists of a number of integrated
      treatment systems, including a 1 ha rafted reed bed canal system and a 2 ha sub
      surface flow gravel reed bed. This research project is concerned with the
      performance of the subsurface flow reed beds, though attention will be paid in
      this paper to the operation of the whole system. Prior to the planting of the
      subsurface flow reed beds, flow-tracing experiments were carried out on the three
      different types of subsurface flow beds, so that the baseline performance of the
      system could be quantified. In association, data regarding the soil organic
      matter content was also collected prior to the planting of the beds. As expected,
      soil organic matter content is observed to be negligible within the bed, though a
      small amount of build up was observed in localised areas on the surface of the
      beds. This was attributed to the growth of algae in depressions where standing
      water persisted during the construction phase. Few studies exist which provide
      detailed measurements into the cause and effect of variations in hydraulic
      conductivity within an operational reed bed system. The data presented here form
      the baseline results for an ongoing study into the investigation of the change in
      hydraulic conductivity of an operational reed bed system.

PMID- 12793679
TI  - Buffer distances for on-site sewage systems in Sydney's drinking water
      catchments.
AB  - Pathogens and nutrients released from on-site sewage systems represent a risk to
      surface and ground water quality, particularly where there are sensitive
      receiving waters such as in drinking water catchments. Buffer zones between on
      site systems and waterways are one barrier used to protect water quality. The
      increased time and distance they provide increases the opportunities for the
      effluent purification functions of the soil to occur. A risk management model is
      proposed to assess the efficacy of the buffer zones in Sydney's drinking water
      catchments. The model is the basis for the development of performance based
      setback distances for on-site systems from waterways, and incorporates stochastic
      analysis of pathogen and nutrient transport in the environment and consideration
      of the effluent quality variability from on-site systems. Catchment-scale
      integration of contaminant transport is employed to facilitate a risk assessment
      of on-site systems. The risk management model also allows for the impact of on
      site system management and maintenance on catchment water quality to be assessed
      through scenario building and feedback mechanisms.

PMID- 12793680
TI  - An integrated water resources management approach for the River Spree and its
      catchment.
AB  - In this paper a concept of an integrated water quality model for a river
      catchment area is presented. The main focus is directed to the development of a
      water quality module for rivers. Necessary simplifications for calculation of
      hydraulics and water quality will be explained. Furthermore, by first simulation
      results possible applications of the model are presented.

PMID- 12793681
TI  - Dryland salinity in Western Australia: managing a changing water cycle.
AB  - Clearing of agricultural land has resulted in significant changes to the surface
      and groundwater hydrology. Currently about 10% of agricultural land in Western
      Australia is affected by dryland salinity and between a quarter and a third of
      the area is predicted to be lost to salinity before a new hydrological
      equilibrium is reached. This paper develops a general statement describing the
      changes to the surface and groundwater hydrology of the wheatbelt of Western
      Australia between preclearing, the year 2000 and into the future. For typical
      catchments in the wheatbelt it is estimated that average groundwater recharge and
      surface runoff have increased about tenfold when comparing the current hydrology
      to that preclearing. Saline groundwater discharge and flood volumes have also
      increased significantly. Saline groundwater discharge and associated salt load
      will probably double in the future in line with the predicted increase in the
      area of dryland salinity. In addition, future increases in the area of dryland
      salinity/permanent waterlogging will probably double the volumes in flood events
      and further increase surface runoff in average years. The outcomes of surface and
      groundwater management trials have been briefly described to estimate how the
      hydrology would be modified if the trials were implemented at a catchment scale.
      These results have been used to formulate possible integrated revegetation and
      drainage management strategies. The future hydrology and impacts with and without
      integrated management strategies have been compared.

PMID- 12793682
TI  - Water quality management in the Kaoping River watershed, Taiwan.
AB  - The Kaoping River basin is the largest and the most intensively used river basin
      in Taiwan. It is 171 km long and drains a catchment of more than 3,250 km2. Based
      on the current water quality analysis, the Kaoping River is heavily polluted.
      Concern about the deteriorating condition of the river led the Government of
      Taiwan to amend the relevant legislation and strengthen the enforcement of the
      discharge regulations to effectively manage the river and control the pollution.
      Investigation results demonstrate that both point and non-point source pollutants
      are now the causes of biochemical oxygen demand (BOD), nutrients, and pathogens
      in the river. The main water pollution sources are livestock wastewater from hog
      farms, municipal wastewater, industrial wastewater, non-point source (NPS)
      pollutants from agricultural areas, and leachate from riverbank landfills. The
      current daily BOD, NH3-N, and TP loadings to Kaoping River are 74,700, 39,400,
      and 5,100 kg, respectively. However, the calculated BOD, NH3-N, and TP carrying
      capacities are 27,700, 4,200, and 600 kg per day. To protect public health and
      improve the river water quality, a comprehensive management and construction
      strategy is proposed. The proposed strategy includes the following measures to
      meet the calculated river carrying capacity: (1) a hog ban in the entire Kaoping
      River basin, (2) sewer system construction to achieve 30% of connection in the
      basin within 10 years, (3) removal of 10 riverbank landfills, and (4) enforcement
      of the industrial wastewater discharge standards. After the implementation of the
      proposed measures, the water quality should be significantly improved and the BOD
      and nutrient loadings can be reduced to below the calculated carrying capacities.

PMID- 12793683
TI  - The Three Rivers Project--water quality monitoring and management systems in the
      Boyne, Liffey and Suir catchments in Ireland.
AB  - The "Three Rivers Project" is a government initiative and one of a series of
      catchment based water quality monitoring and management systems being developed
      throughout Ireland since 1997. The establishment of these multi-sectoral, basin
      wide and community based systems is a response to historically perceived
      disjointed, legalistic and non-participative approaches to water resource
      management and purports to transcend the restrictions of traditional local
      authority administrative boundaries. The new management model embodies the
      concepts and objectives contained in the European Union (EU) Water Framework
      Directive (WFD) enacted in December 2000. Ireland, in common with many EU
      countries, has failed to halt decades of increasing levels of eutrophication of
      surface waters due principally to phosphorus loading. The "Three Rivers Project"
      is promoting the benefits of an integrated and cooperative approach to the
      management of three important river systems in Ireland, namely, the Boyne, Liffey
      and Suir. The project objective is to protect and improve water quality to
      conform with "good ecological status". The implications of the Project findings
      for agricultural, municipal and industrial policy are grave and one of the
      greatest challenges now is to organise and fund Irish River Basin Management
      Systems as envisaged by the WFD to continue and build on the work which the
      "Three Rivers Project" has undertaken.

PMID- 12793684
TI  - Evaluation of factors influencing diffusion of pollutant loads in urban highway
      runoff.
AB  - Many studies have identified the first flush phenomenon and runoff
      characteristics. The purpose of this study is to elucidate which parameters
      influence the runoff pollutant loads. Eight runoff events during the period from
      May 1999 to September 2000 were investigated. From the dimensionless cumulative
      analysis, it was suggested that particulate substances such as suspended solids
      (SS), iron and total phosphorus (T-P) were inclined to be washed off in heavier
      rainfall condition. The cumulative curves of particulate constituents were
      appreciably variable in slope, while those of dissolved were approximately
      constant. Accordingly it was indicated that dissolved load was discharged
      regardless of rainfall conditions. Event mean runoff intensity and cumulative
      runoff height showed significant correlation with the cumulative runoff load of
      the constituents except for total nitrogen (T-N). On the other hand, antecedent
      dry weather period (ADWP) and traffic flow volume during ADWP did not show
      correlation with the cumulative runoff loads. Only T-N load showed correlation
      with those factors, consequently it was suggested that vehicular exhausts
      affected nitrogen load on the surface of urban highway.

PMID- 12793685
TI  - Assessment of sediment toxicity by metal speciation in different particle-size
      fractions of river sediment.
AB  - Mobility and toxicity of metals associated with sediments are generally affected
      by metal speciation and granular compositions. Due to the various speciation
      patterns of heavy metals in sediments, it is not reliable to assess the potential
      toxicity of heavy metals on the aquatic environment with the total concentrations
      of heavy metals in sediments. The purposes of this study were to investigate the
      distribution of metal speciation in different particle-size fractions of
      sediments collected from two rivers (the Ke-Ya River and Ell-Ren River) in
      Taiwan, and to assess their potential toxicity to the aquatic ecosystem. Metals
      in the exchangeable, carbonate-bound and Fe/Mn oxide-bound forms obtained by
      sequential extraction were considered to be mobile and related with anthropogenic
      pollution. The degree of metal pollution and potential toxicity of sediments were
      higher in the lower reaches of both rivers. The metal speciation in sediments had
      a bimodal distribution over particle-size fractions. Heavy metals were subject to
      accumulation in the silt/clay fraction (< 25 microm) and coarse sand (420-2,000
      microm). By normalizing the sum of the exchangeable, carbonate-bound, and Fe/Mn
      oxide-bound metals, it suggested that the potential toxicity to the aquatic
      ecosystem was caused by the fine sediments as well as coarse sediments.

PMID- 12793686
TI  - Effect of non-aqueous phase liquid on biodegradation of PAHs in spilled oil on
      tidal flat.
AB  - Biodegradation rates of polycyclic aromatic hydrocarbons (PAHs) in spilled oil
      stranded on tidal flats were studied using model reactors to clarify the effects
      of NAPL on the biodegradation of PAHs in stranded oil on tidal flat with special
      emphasis on the relationship between dissolution rates of PAHs into water and
      viscosity of NAPL. Biodegradation of PAHs in NAPL was limited by the dissolution
      rates of PAHs into water. Biodegradation rate of chrysene was smaller than that
      for acenaphthene and phenanthrene due to the smaller dissolution rates.
      Dissolution rates of PAHs in fuel oil C were smaller those in crude oil due to
      high viscosity of fuel oil C. Therefore, biodegradation rates of PAHs in fuel oil
      C were smaller than those in crude oil. Biodegradation rates of PAHs in NAPL with
      slow decrease rate like fuel oil C were slower than those in NAPL with rapid
      decrease like crude oil. The smaller decrease rate of fuel oil C than crude oil
      was due to higher viscosity of fuel oil C. Therefore, not only the dissolution
      rate of PAHs but also the decrease rates of NAPL were important factors for the
      biodegradation of PAHs.

PMID- 12793687
TI  - Emissions of heavy metals into river basins of Germany.
AB  - The input of seven heavy metals (Cd, Cr, Cu, Hg, Ni, Pb and Zn) into the large
      river basins of Germany via various point and diffuse pathways were estimated for
      the period of 1985 through 2000. To quantify the emissions via point sources a
      nationwide survey on heavy metal data of municipal wastewater treatment plants
      and industrial direct discharges was carried out. The input via diffuse pathways
      was calculated using an adapted version of the model MONERIS. This model accounts
      for the significant transport processes, and it includes a Geographical
      Information System (GIS) that provides digital maps as well as extensive
      statistical information. For a comparison of the calculated heavy metal emission
      with the measured heavy metal load at monitoring stations the losses of heavy
      metals due to retention processes within the river systems have to be considered.
      Therefore heavy metal retention was calculated according to the retention
      functions given by Vink and Behrendt. For the large river basins a good
      correspondence could be found between estimated and measured heavy metal loads in
      rivers. The total emission into the North Sea decreased for each metal during the
      period of 1986 to 2000. The reduction varies between 87% for Hg and 41% for Ni
      mainly caused by the decline via point sources. Today's emissions of heavy metals
      into river basins of Germany are dominated by the input via diffuse pathways. The
      most important diffuse emission pathways are "paved urban areas" and "erosion".

PMID- 12793688
TI  - Pollution potential of oil-contaminated soil on groundwater resources in Kuwait.
AB  - The only natural freshwater resource of Kuwait occurs as lenses floating on the
      saline groundwater in the northern part of the country, near to the oil fields.
      Rainwater is the only means of recharge of this limited groundwater resource.
      This groundwater is used as bottled drinking water and the fresh groundwater
      aquifer is considered as a strategic drinking water reserve for Kuwait. As a
      result of the 1991 Gulf War, the upper soil layer has been widely contaminated
      with crude oil and crude oil combustion products, which are potential pollutants
      likely affecting the groundwater resources. Significant efforts have been made to
      assess this pollution. These included: (a) a soil survey for assessing the soil
      contamination, and (b) leaching experiments to characterise the mobilization of
      the soil-associated pollutants. Fluorescence measurement techniques were used
      during field surveys as well as for laboratory testing. In addition,
      determination of the total extractable matter (TEM), total petroleum hydrocarbons
      (TPH), and GC/MS measurement of polyaromatic hydrocarbons (PAHs) were performed
      for the assessments. The laser induced fluorescence (LIF) measurement, having
      good correlation with the other laboratory measurements, was proved to provide
      necessary information for the assessment of the oil-contamination level in the
      desert soil. The subsequent leaching test with water demonstrated the
      mobilization of the fluorescing compounds (e.g. PAHs), and the alteration in the
      leaching characteristics of the contamination during the long-term environmental
      weathering of the oil.

PMID- 12793689
TI  - The PPL filtration treatment for highway runoff.
AB  - The purpose of this research is to design a device which can treat highway
      runoff, especially runoff during initial rainfall with high pollution intensity,
      by connecting it with the draining grid sink of a drainage ditch on a highway,
      through which runoff flows. Porous polypropylene (PPL) particles were used as a
      treatment agent. The device treated highway runoff during initial rainfall by
      filtration and adsorption. It had a capacity to treat highway runoff in an area
      of 7.0 m x 20.0 m when rainfall intensity was up to 10 mm/hr. Two cases of
      rainfall intensity were set for the experiment: 5 and 10 mm/hr. The relationships
      between the efficiency of SS and COD removals and the rainfall intensity were
      investigated. Using artificial highway runoff with constant flow and SS
      concentration, results of 70% or more of SS removal with 5 mm/hr and 50% or more
      with 10 mm/hr were obtained. COD removal efficiency was about 90% of SS removal
      efficiency. This device was effective to remove non-point source pollutants in
      runoff on highways.

PMID- 12793690
TI  - Agricultural land use and N losses to water: the case study of a fluvial park in
      northern Italy.
AB  - An integrated water resource management programme has been under way since 1999
      to reduce agricultural water pollution in the River Mincio fluvial park. The
      experimental part of the programme consisted of: a) a monitoring phase to
      evaluate the impact of conventional and environmentally sound techniques (Best
      Management Practices, BMPs) on water quality; this was done on four
      representative landscape units, where twelve fields were instrumented to monitor
      the soil, surface and subsurface water quality; b) a modelling phase to extend
      the results obtained at field scale to the whole territory of the Mincio
      watershed. For this purpose a GIS developed in the Arc/Info environment was
      integrated into the CropSyst model. The model had previously been calibrated to
      test its ability to describe the complexity of the agricultural systems. The
      first results showed a variable efficiency of the BMPs depending on the
      interaction between management and pedo-climatic conditions. In general though,
      the BMPs had positive effects in improving the surface and subsurface water
      quality. The CropSyst model was able to describe the agricultural systems
      monitored and its linking with the GIS represented a valuable tool for
      identifying the vulnerable areas within the watershed.

PMID- 12793691
TI  - Determination of faecal pollutants in Torrens and Patawalonga catchment waters in
      South Australia using faecal sterols.
AB  - This research investigated faecal pollution by sterol profiling in two Adelaide
      metropolitan catchments in winter 2000 and summer 2001. Water was sampled from
      five sites on the River Torrens and two sites on Patawalonga river catchment. The
      steroids detected were coprostanol, epicoprostanol, cholesterol, cholestanol,
      stigmasterol, betasitosterol, and stigmastanol. The concentrations range from 5
      ng/L (of coprostanol) to 34 microg/L (of stigmasterol), with cholesterol detected
      more frequently at relatively high concentrations (approximately 2 microg/L).
      Sterol profiling suggested two sites on two occasions may have been impacted by
      human faecal contamination. Other steroid profiles suggested that sources of
      pollution consistently included dogs and birds. The steroid concentrations in the
      Torrens catchment were higher in winter, however, this was not observed in the
      Patawalonga catchment.

PMID- 12793692
TI  - Accounting for water quality effects of future urbanization: diffuse pollution
      loads estimates and control in Mantua's lakes (Italy).
AB  - The three shallow lakes of Mantua (Upper, Middle and Lower) formed by the Mincio
      River are today classified by Italian water authorities as sensitive areas,
      after, in the second half of the 20th century, the hydrologic regime of the lakes
      was heavily modified, and the influence of industrial activities operating in the
      1960s--without much environmental consideration--created a substantial decline in
      the water quality of the lakes. The City of Mantua is one of the most vital
      industrial centers of Northern Italy, and development plans are under way, that
      should approximately double the extension of the urban and industrial area within
      the next 20 years. This paper deals with estimating the effects of the
      aforementioned urbanization on the future water quality of the three lakes.

PMID- 12793693
TI  - Effects of seasonal variation in precipitation on estimation of non-point source
      pollution.
AB  - The extent of nonpoint source pollution (NPSP) generated from upstream catchment
      areas of a reservoir is normally estimated based on a design rainfall. However,
      rainfall generally varies in different seasons. This seasonal change may
      significantly influence the estimation of runoff volume and associated NPSP
      arising within a reservoir watershed. The NPSP management, reservoir operation,
      and water treatment operation strategies developed based on the estimation will
      also be altered. This study analyzes the effects of monthly and seasonal
      variation in precipitation on the estimation of pollution levels from nonpoint
      sources in a reservoir watershed. The area studied is the Derchi reservoir
      watershed located in central Taiwan. This watershed is subdivided into twenty-six
      sub-watersheds, and the Thiessen method is used to determine the rainfall
      intensity in each sub-watershed. Runoff pattern and NPSP contributions for each
      sub-watershed are estimated using the AGNPS model. Results show significant
      seasonal variation in precipitation; estimated NPSP loads likewise vary
      significantly over time. Seven- to one hundred-fold differences among monthly and
      seasonal estimations of phosphorus and sediment loads are observed.

PMID- 12793694
TI  - Strategic management of non-point source pollution from sewage sludge.
AB  - In the UK, the recycling of sewage sludge to land is expected to double by 2006
      but the security of this route is threatened by environmental concerns and health
      scares. Strategic investment is needed to ensure sustainable and secure sludge
      recycling outlets. At present, the security of this landbank for sludge recycling
      is determined by legislation relating to nutrient rather than potentially toxic
      elements (PTEs) applications to land--especially the environmental risk linked to
      soil phosphorus (P) saturation. We believe that not all land has an equal risk of
      contributing nutrients derived from applications to land to receiving waters. We
      are currently investigating whether it is possible to minimise nutrient loss by
      applying sludge to land outside Critical Source Areas (CSAs) regardless of soil P
      Index status. Research is underway to develop a predictive and spatially
      sensitive, semi-distributed model of critical thresholds for sludge application
      that goes beyond traditional "end-of-pipe" or "edge-of-field" modelling, to
      include hydrological flow paths and delivery mechanisms to receiving waters from
      non-point sources at the catchment scale.

PMID- 12793695
TI  - A comparative analysis: storm water pollution policy in California, USA and
      Victoria, Australia.
AB  - Urban drainage systems historically were developed on principles of hydraulic
      capacity for the transport of storm water to reduce the risk of flooding.
      However, with urbanization the percent of impervious surfaces increases
      dramatically resulting in increased flood volumes, peak discharge rates,
      velocities and duration, and a significant increase in pollutant loads. Storm
      water and urban runoff are the leading causes of the impairment of receiving
      waters and their beneficial uses in Australia and the United States today. Strict
      environmental and technology controls on wastewater treatment facilities and
      industry for more than three decades have ensured that these sources are less
      significant today as the cause of impairment of receiving waters. This paper
      compares the approach undertaken by the Environmental Protection Authority
      Victoria for the Melbourne metropolitan area with the approach implemented by the
      California Environmental Protection Agency for the Los Angeles area to control
      storm water pollution. Both these communities are largely similar in population
      size and the extent of urbanization. The authors present an analysis of the
      different approaches contrasting Australia with the USA, comment on their
      comparative success, and discuss the relevance of the two experiences for
      developed and developing nations in the context of environmental policy making to
      control storm water and urban runoff pollution.

PMID- 12793696
TI  - Estimation of urban runoff and water quality using remote sensing and artificial
      intelligence.
AB  - Water quality and quantity of runoff are strongly dependent on the landuse and
      landcover (LULC) criteria. In this study, we developed a more improved parameter
      estimation procedure for the environmental model using remote sensing (RS) and
      artificial intelligence (AI) techniques. Landsat TM multi-band (7bands) and Korea
      Multi-Purpose Satellite (KOMPSAT) panchromatic data were selected for input data
      processing. We employed two kinds of artificial intelligence techniques, RBF-NN
      (radial-basis-function neural network) and ANN (artificial neural network), to
      classify LULC of the study area. A bootstrap resampling method, a statistical
      technique, was employed to generate the confidence intervals and distribution of
      the unit load. SWMM was used to simulate the urban runoff and water quality and
      applied to the study watershed. The condition of urban flow and non-point
      contaminations was simulated with rainfall-runoff and measured water quality
      data. The estimated total runoff, peak time, and pollutant generation varied
      considerably according to the classification accuracy and percentile unit load
      applied. The proposed procedure would efficiently be applied to water quality and
      runoff simulation in a rapidly changing urban area.

PMID- 12793697
TI  - Field monitoring and evaluation of innovative solutions for cleaning storm water
      runoff.
AB  - Urbanization increases the variety and amount of pollutants transported to
      receiving waters. Sediment from development and new construction; oil, grease,
      and toxic chemicals from automobiles; nutrients and pesticides from turf
      management and gardening; viruses and bacteria from failing septic systems; road
      salts; and heavy metals are examples of pollutants generated in urban areas.
      Sediments and solids constitute the largest volume of pollutant loads to
      receiving waters in urban areas. When runoff enters storm drains, it carries many
      of these pollutants with it. In older cities, this polluted runoff is often
      released directly into open waterways without any treatment. Increased pollutant
      loads can harm fish and wildlife populations, kill native vegetation, foul
      drinking water supplies, and make recreational areas unsafe. The objective of the
      study, performed by University of Pavia (Italy), University of Brescia (Italy)
      and GreenTechTexas International (US), reported herein is to evaluate the use of
      an innovative stormwater technology (EcoDrain) to reduce pollution due to urban
      runoff in existing urban areas. The paper describes the methodology and the
      results achieved with tests conducted in laboratory in Pavia University in Italy
      and in two pilot areas in Italy and in Australia to investigate the EcoDrain's
      effectiveness for oil and heavy metals retention and sediment trapping. In the
      tests performed in a marina near Sydney in Australia a reduction has been
      achieved in oil and grease concentration higher than 95% and a reduction in metal
      concentration (particularly Copper, Lead and Zinc) close to 98%. The paper also
      describes the methodology of the analysis on the absorbing material after its use
      and the consequent determination of the most efficient and environmentally safe
      way to dispose of consummated absorbent.

PMID- 12793698
TI  - The vortex concentrator for suspended solids treatment.
AB  - The use of vortex concentrators is becoming increasingly popular for suspended
      solids reduction in combined sewer overflows and stormwater. This study is a
      laboratory investigation of the use of vortex concentrators to reduce the solids
      concentration of synthesized stormwater. The synthesized stormwater was made with
      water and addition of particles; sand, granular activated carbon, and sewer
      sediments. The vortex concentrator was made of acryl resin 300 mm in diameter. To
      determine the efficiency for various influent suspended solids (SS)
      concentrations, tests were performed with different SS concentrations. The
      samples were taken simultaneously at the influent storage tank and effluent tank,
      and measured SS concentrations. The range of surface loading rates were 120 to
      850 m3/m2/day, and influent SS concentrations were varied from 300 to 5,000 mg/L.
      To determine the optimum coagulant dosage, jar tests were conducted with
      coagulants such as PAM and PAC. It was found that optimum coagulant and its
      dosage were PAM and 2 mg/L. The overall SS removal efficiency of the vortex
      concentrator for typical stormwater was estimated at about 65%. With an increase
      of SS concentration, the removal efficiency was increased. Since the SS
      concentration of stormwater was higher than 1,000 mg/L, the removal efficiency of
      the vortex concentrator for stormwater could be estimated to be 65-70%. The SS
      removal efficiency was increased with an increase of retention time, and the
      optimum retention time was 0.15-1.0 minutes. With an increase of the foul to
      overflow Q(F)/Q(o), a key parameter for vortex concentrator operation, the
      removal efficiency was increased. An alternative solution to improve treatment
      efficiency might be to set a follow-up retention basin. Based on a series of
      settling tests on the treated overflow water from the vortex concentrator, 5 to
      10 minutes hydraulic retention time in a follow-up retention basin would
      substantially improve the results.

PMID- 12793699
TI  - Changes in water quality parameters due to in-sewer processes.
AB  - Combined sewer systems contain a large number of organic and inorganic pollutants
      from both domestic and industrial sources. These pollutants are often retained
      within the combined sewer system for significant lengths of time before entering
      sewage treatment works, or being spilt to a watercourse via a combined sewer
      overflow (CSO) during storm conditions. Currently little knowledge exists
      concerning the effects of in sewer processes on pollutants. Understanding of in
      sewer processes is important for the effective and efficient design of treatment
      works and CSO chambers and for impact assessments on receiving waters. A series
      of studies covering storm and dry weather flow conditions were undertaken with
      the aim of investigating the nature of in-sewer processes. These studies
      consisted of marking a body of water with a fluorescent tracer. The tracer was
      then monitored at a series of downstream sites, and discrete samples collected
      from the body of water as it progressed through the sewer. The samples were
      analysed for water quality parameters and these results investigated in tandem
      with the detailed hydraulic information gained through the tracer studies. The
      results highlight the hydraulic differences between storm and dry weather
      conditions such as increased travel times and mixing under storm conditions. The
      Advection Dispersion Equation (ADE) and Aggregated Dead Zone (ADZ) model
      parameters have been quantified for the tracer data. The ADE mixing coefficient
      is shown to increase by an order of magnitude for storm conditions. The ADZ
      dispersive fraction parameter is shown to be approximately constant with flow.
      Chemical reactions and decay within the sewer system were found to be consistent
      with oxygen limitation.

PMID- 12793700
TI  - Research of the flow procedures in a pressure sewer system.
AB  - At the Institute of Land Reclamation, Hydrology and Sanitary Engineering of the
      University at Rostock the pressure and flow ratios are examined within a
      measuring section in the pressure dewatering system on the Darss peninsula. The
      objective of the research project is the knowledge upgrade about the highly
      unsteady hydraulic conditions in a pressure sewer system. This paper firstly
      presents the method and the dimensioning of pressure dewatering systems, which
      can be done using either the peak effluent method or the statistical method; the
      examination program will be explained. The examination includes pressure
      difference measuring with two pressure meters and flow data measuring via
      magnetic-inductive flow meters. Additionally the pump running times of 15 pumping
      stations, as well as the compressor action of the pressure pipe rinsing station
      are continuously and temporarily recorded and saved. Finally the measuring
      results which provide initial information about the pressure and flow conditions
      in a pressure dewatering system will be presented. The effects of the rinsing,
      the low pressure differences, the air cushions, the seasonal differences as well
      as the daily development graphs of the wastewater production are all clearly
      visible.

PMID- 12793701
TI  - Prevention of odour emergence in sewage networks.
AB  - Through increasing central development and through the decrease of specific
      wastewater production, wastewater systems are more and more prone to odour and
      corrosion problems. Hydrogen sulphide is produced, particularly in anaerobic flow
      stretches, which will then escape at turbulent places because of change in the
      flow direction and create odour harassment. Of particular importance in this
      respect are the transferring shafts after rising mains. The empirical approaches
      used for the estimation of the assumed sulphide concentrations yield considerable
      differences in the calculation and must therefore be used with care. This report
      presents a methodology for the co-ordination of odour- and corrosion-reducing
      measures which also includes the area of complaint management. It is crucially
      important to fine-tune the necessary measures (for instance the application of
      operational or chemical/biological methods) to the specific frame conditions. The
      practical comparison of the additional dosage of external water, iron and nitrate
      served to test the efficiency of these methods. The dosage of iron and nitrate
      led to considerable reductions in H2S content at the transferring shaft. The
      online measurement of the spectral adsorption coefficient (SAC) could become one
      control parameter for saving chemicals. It should be pointed out that it is
      necessary to consider the relevant measures and effects of odour and corrosion
      production during the planning stage--from the creation of the development plan
      of cities and communities. Through the selection of the wastewater disposal
      method to the planning of details. Moreover, the relevant financial means for
      these measures must be included in the economic plan.

PMID- 12793702
TI  - Real time control of a combined sewer system using radar-measured precipitation-
      results of the pilot study.
AB  - Emschergenossenschaft and Lippeverband have developed a method to use radar
      measured precipitation as an input for a real-time control of a combined sewer
      system containing several overflow structures. Two real-time control strategies
      have been developed and tested, one is solely volume-based, the other is volume
      and pollution-based. The system has been implemented in a pilot study in
      Gelsenkirchen, Germany. During the project the system was optimised and is now in
      constant operation. It was found, that the volume of combined sewage overflow
      could be reduced by 5 per cent per year. This was also found in simulations
      carried out in similar catchment areas. Most of the potential of improvement can
      already be achieved by local pollution-based control strategies.

PMID- 12793703
TI  - Chronic hepatitis C infection and peripheral neuropathy; is mixed
      cryoglobulinemia really important?

PMID- 12793704
TI  - Does hepatocellular carcinoma develop after treatment of Wegener's granulomatosis
      with cyclophosphamide?

PMID- 12793705
TI  - Neuropathological findings in hypereosinophilic syndrome.

PMID- 12793706
TI  - Heart failure in the elderly.
AB  - Heart failure is common in the elderly population. Approximately 6 to 10 percent
      of the population 65 years or older have heart failure. Heart failure is the most
      common reason for hospitalization in elderly patients. Etiology of heart failure
      is often multifactorial in the elderly. The common causes of heart failure
      include ischemic heart disease, valvular heart disease, hypertensive heart
      disease, and cardiomyopathy. Exacerbation of heart failure in the elderly is
      often accompanied by precipitating factors which include arrhythmia, renal
      failure, anemia, infection, adverse effect of drugs and non-compliance with
      medication and/or diet. Diagnosis of heart failure may be difficult in the
      elderly because symptoms of heart failure are often atypical or even absent.
      Heart failure with preserved systolic function is common in the elderly because
      aging has a greater impact on diastolic function. It is important to recognize
      that very old patients with heart failure are underrepresented in clinical
      trials.

PMID- 12793707
TI  - Analysis of risk factors for hepatocellular carcinoma that is negative for
      hepatitis B surface antigen (HBsAg).
AB  - OBJECTIVE: To clarify risk factors for hepatocellular carcinoma (HCC) other than
      hepatitis B surface antigen (HBsAg). PATIENTS AND METHODS: We investigated serum
      HBV-DNA and other factors in 146 patients with liver cirrhosis (LC) or HCC who
      were HBsAg negative. We analyzed the clinical background of the patients, status
      of hepatitis B (HBV) viral markers and platelet count as well as the presence of
      an HBV-DNA fragment by PCR and elucidated risk factors for HCC generation using a
      logistic regression model. RESULTS: Among ten factors, we determined that four
      represented a significant risk for HBsAg negative HCC: male gender, total alcohol
      consumption, total cigarettes smoked, and the presence of an HBV-DNA fragment.
      Multivariate analysis showed that among the four factors, the HBV-DNA fragment
      was an independent factor associated with HCC. CONCLUSION: The presence of an HBV
      DNA fragment irrespective of the status of antibodies to either HBsAg (anti-HBs)
      or hepatitis B core antigen (anti-HBc) is a pivotal factor associated with the
      development of HCC.

PMID- 12793708
TI  - Peripheral neuropathy in Japanese patients with hepatitis C virus infection.
AB  - OBJECTIVE: The aim of this study was to report a series of Japanese patients with
      neuropathic symptoms following HCV infection. PATIENTS AND METHODS: Fifteen
      patients with neuropathic symptoms and HCV infection were studied retrospectively
      (neuropathy group). We evaluated clinical and electrophysiologic findings. As a
      control group, we investigated prospectively 11 patients with chronic HCV
      hepatitis without neuropathic symptoms. RESULTS: In the neuropathy group, the
      peripheral neuropathy was a multiple mononeuropathy (MM) in 8 patients, a
      polyneuropathy in 4 patients, a single cranial neuropathy in 2 patients, and a
      cervical radiculopathy in one patient. Five patients with MM had relapsing
      symptoms. Two patients showed a progression of neurologic symptoms following
      varicella zoster virus infection. Mixed cryoglobulinemia was noted in 4 of 13
      tested patients. Circulating immunocomplexes were detected in 3 of 10 tested
      patients, and low complement (C3, C4, or CH50) levels were noted in 10 of 13
      tested patients. Nerve conduction study (NCS) showed abnormal findings in 10 of
      13 investigated patients. In the control group, only the frequency of low CH50
      was significantly lower than that in the neuropathy group. Abnormal findings of
      NCS were found in 3 of 11 patients. CONCLUSION: We showed the presence of various
      types of neuropathies in patients with HCV infection. Our results suggest that
      relapsing MM is common in HCV positive neuropathy with or without
      cryoglobulinemia, and that the virus may modulate neurologic manifestations of
      other viral infections. Subclinical neuropathy may be present in some patients
      with HCV infection without neurologic symptoms.

PMID- 12793709
TI  - Phenol Congo red staining enhances the diagnostic value of abdominal fat
      aspiration biopsy in reactive AA amyloidosis secondary to rheumatoid arthritis.
AB  - OBJECTIVE: Systemic reactive AA amyloidosis is an intractable complication in
      patients with a long history of rheumatoid arthritis (RA). To help to more easily
      and reliably detect the presence of this form of amyloidosis in patients with RA
      and start intensive treatment as early as possible, we examined the sensitivity
      and usefulness of abdominal fat aspiration biopsy with phenol Congo red staining
      in the diagnosis of AA amyloidosis. PATIENTS AND METHODS: Ten patients were
      diagnosed with systemic reactive AA amyloidosis secondary to RA (all women; mean
      age, 70.2 +/- 6.4 years; mean disease duration of RA, 20.3 +/- 11.2 years) based
      on histopathological examinations of biopsied specimens mainly from the
      gastroduodenal mucosa. Abdominal fat aspiration biopsy was performed in these
      patients, and the specimens were treated with both classical alkaline and phenol
      Congo red staining. RESULTS: Phenol Congo red staining revealed amyloid deposits
      in all 10 patients, while conventional alkaline Congo red staining showed a
      positive result in 7 patients. In the patients with a positive result with
      alkaline Congo red staining, reactivity of one grade or two higher was
      demonstrated by the phenol Congo red method. CONCLUSION: Phenol Congo red
      staining is superior to the classical alkaline Congo red staining with respect to
      the detection of AA-amyloid deposits in biopsied abdominal fat tissue specimens.
      In addition to easy access and procedural safety, abdominal fat aspiration biopsy
      might contribute reliably to the diagnosis of systemic reactive AA amyloidosis
      secondary to RA when phenol Congo red staining is employed.

PMID- 12793710
TI  - Hepatocellular carcinoma associated with long-term cyclophosphamide therapy for
      Wegener granulomatosis.
AB  - The development of hepatocellular carcinoma (HCC) requires persistent hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infection. The other origins are
      extremely rare. A 63-year-old woman was admitted to our hospital for work-up of
      hepatic mass. She took cyclophosphamide for Wegener granulomatosis for 21 years.
      Serum HBV and HCV markers were negative. A diagnosis of HCC was made by the
      imaging findings, and an extended left lobectomy of the liver was performed.
      Histologically, the tumor was diagnosed as moderately differentiated HCC. We thus
      considered the HCC in this case as a complication of the long-term
      cyclophosphamide by the absence of known causes of HCC.

PMID- 12793711
TI  - Preclinical Cushing's syndrome presenting with isolated adrenocorticotropin
      (ACTH) deficiency-like manifestations and severe hypoalbuminemia without overt
      adrenal masses in a patient with Chilaiditi syndrome and mental retardation.
AB  - A 52-year-old man with Chilaiditi syndrome and mental retardation was admitted to
      Kanagawa Rehabilitation Hospital for severe hypoglycemic coma with malnutrition.
      This patient was first diagnosed as partial isolated adrenocorticotropin
      deficiency according to his symptoms and clinical course, but he was finally
      diagnosed as preclinical Cushing's syndrome. Manifestations of this case seemed
      unusual in spite of autonomic cortisol secretion and the detailed mechanisms of
      symptoms were unclear. The present case indicates that preclinical Cushing's
      syndrome may present with various manifestations, and careful diagnosis is
      necessary.

PMID- 12793713
TI  - Streptococcal toxic shock syndrome presenting with spontaneous hypoglycemia in a
      chronic hemodialysis patient: pathophysiological mechanisms.
AB  - Hypoglycemia is fatal if associated with sepsis in end-stage renal disease (ESRD)
      patients. We report a hemodialysis patient of streptococcal toxic shock syndrome
      presenting with hypoglycemia. She was found to be severely hypoglycemic with a
      plasma glucose level of 16 mg/dl. Immunoreactive insulin levels were undetectable
      throughout the clinical course. Several factors including reduced renal
      gluconeogenesis, reduced hepatic glucose output and excessive peripheral glucose
      utilization may account for the hypoglycemia in this patient. In conclusion, we
      would like to draw attention to the fact that septic ESRD patients without
      diabetes are prone to develop profound hypoglycemia with serious consequences.

PMID- 12793712
TI  - Decompensated hepatitis B virus-related cirrhosis successfully treated with
      lamivudine allowing surgery for hepatocellular carcinoma.
AB  - A 39-year-old man was diagnosed with hepatitis B virus-related cirrhosis, and
      because of hepatic exacerbations with icterus and ascites, he had been repeatedly
      hospitalized. He was treated with lamivudine. Several months later, his ascites
      disappeared and his liver function was improved from class C to A according to
      the Child-Pugh classification. Two years later, one small hepatocellular
      carcinoma was detected, and he underwent a successful hepatectomy. From this
      case, we consider lamivudine to be useful for improving hepatic function in
      decompensated liver cirrhosis type B and lamivudine might enable surgical
      resection of hepatocellular carcinoma.

PMID- 12793714
TI  - Spontaneous remission of a massive CNS inflammation with eosinophilic infiltrate.
AB  - We report a case of spontaneous remission of a massive CNS lesion with
      eosinophilic infiltrate. This 69-year-old man had eosinophilia without any
      systemic disorder or laboratory evidence of the most common causes of
      hypereosinophilia. MRI of the brain suggested an infiltrating neoplasm, but
      histological examination of a needle biopsy specimen failed to show evidence of a
      neoplasm. Instead, the tissue demonstrated rarefaction and gliosis with striking
      perivascular and parenchymal infiltrates of eosinophils. The MRI abnormality and
      eosinophilia disappeared spontaneously. We speculate that eosinophil-derived
      neurotoxins might have been the cause of the transient CNS disorder observed in
      this patient.

PMID- 12793715
TI  - Steroid-responsive limbic encephalitis.
AB  - A 71-year-old man presented with gradually progressing cognitive decline
      following acute febrile exanthematous disorder. The MRI showed an abnormality in
      the bilateral limbic systems. An elevation of cerebrospinal fluid (CSF) protein
      with lymphocyte pleocytosis was noted. Immunoblot of the CSF revealed the
      presence of anti-white matter antibodies that mainly recognized astrocytes.
      Intravenous steroid followed by oral steroid reduced the symptoms to a remarkable
      degree. The patient has now been successfully sustained with steroid for more
      than two years. We considered that this case is classified as non-paraneoplastic
      limbic encephalitis, and acquired autoimmunity played a major role in the
      pathogenesis of this case.

PMID- 12793716
TI  - Dissecting aneurysm of the anterior cerebral artery with severe subarachnoid
      hemorrhage during treatment for cerebral infarction.
AB  - Intracranial dissecting aneurysms cause ischemia, but anticoagulation or
      antiplatelet agents are administered to most ischemic patients without
      angiographical investigation. A 55-year-old woman succumbed to a subarachnoid
      hemorrhage (SAH) during antiplatelet therapy for ischemia caused by a dissecting
      aneurysm at the anterior cerebral artery, which was identified by conventional
      angiography on day 11 after admission. The authors emphasize that all dissecting
      aneurysms manifesting ischemic attack can cause hemorrhage. Therefore, emergency
      angiography is recommended for patients with ischemia complaining of a headache.
      If dissection is identified, it may be better to regulate the blood pressure of
      the patient strictly without anticoagulation or antiplatelet therapy.

PMID- 12793717
TI  - Adult onset anaphylactoid purpura with severe gastrointestinal involvement.
AB  - We treated a case of adult-onset severe-form anaphylactoid purpura. This case had
      been diagnosed as anaphylactoid purpura pathologically by skin biopsy. However,
      his clinical manifestations were atypical in view of complicated massive
      gastrointestinal hemorrhage. Intensive therapy including corticosteroid and
      cyclophosphamide transiently improved his condition. Nevertheless, the beta-D
      glucan value in peripheral blood was gradually elevated. Prophylactic use of
      fluconazole failed to prevent contraction of invasive mycosis. Finally, he
      suddenly suffered from diffuse cerebral hemorrhage. Postmortem examination
      revealed systemic invasive aspergillosis as the cause of death.

PMID- 12793718
TI  - A patient with Takayasu's arteritis treated with corticosteroids who developed
      primary biliary cirrhosis.
AB  - A 40-year-old woman with a history of fever and arthralgia since age 17 had
      received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's
      arteritis in 1980 and given PSL. The symptoms were well controlled until she
      developed itching in 1998. Laboratory tests showed elevated levels of aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma
      glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested
      positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate
      dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis
      (PBC). Our patient's clinical course suggested that an adequate amount of PSL to
      control Takayasu's arteritis does not necessarily prevent the development of PBC.

PMID- 12793719
TI  - Antibody to hepatitis B surface antigen (anti-HBs) induced by a recombinant
      hepatitis B vaccine consisting of subtype adr antigen is underestimated on the
      World Health Organization (WHO)-standardized assay.

PMID- 12793720
TI  - Kaposi's sarcoma in a human immunodeficiency virus-negative patient treated with
      corticosteroid for idiopathic thrombocytopenic purpura.

PMID- 12793721
TI  - Right atrial tumor and sick sinus syndrome.

PMID- 12793722
TI  - How do we get from cell and animal data to risks for humans from space
      radiations?
AB  - After four decades of human exploration in space, many scientists consider the
      medical consequences from radiation exposures to be the major biological risk
      associated with long-term missions. This conclusion is based upon results from a
      research program that has evolved over the past thirty years. Despite the
      diversity in both opinions and approaches that necessarily arise in research
      endeavors such as this, a commonality has emerged from our community. We need
      epidemiological data for humans, animal data in areas where no human data exist,
      and data on mechanisms to get from animal to humans. We need a programmatic
      infrastructure that addresses specific goals as well as basic research. These
      concepts might be deemed overly simplistic and even tautologous were it not for
      the fact that they are frequently underutilized and even ignored. This article
      examines the goals, premises, and infrastructures proposed by expert panels and
      agencies to address radiation risks in space. It is proposed that the required
      level of effort and the resources available demand a unified, focused
      international effort that is, at the same time, subjected to rigorous peer review
      if it is to be successful. There is a plan; let us implement it.

PMID- 12793723
TI  - Studies about space radiation promote new fields in radiation biology.
AB  - Astronauts are constantly exposed to space radiation of various types of energy
      with a low dose-rate during long-term stays in space. Therefore, it is important
      to determine correctly the biological effects of space radiation on human health.
      Studies about biological the effects at a low dose and a low dose-rate include
      various aspects of microbeams, bystander effects, radioadaptive responses and
      hormesis which are important fields in radiation biology. In addition, space
      radiations contain high linear energy transfer (LET) particles. In particular,
      neutrons may cause reverse effectiveness at a low dose-rate in comparison to
      ionizing radiation. We are also interested in p53-centered signal transduction
      pathways involved in the cell cycle, DNA repair and apoptosis induced by space
      radiations. We must also study whether the relative biological effectiveness
      (RBE) of space radiation is affected by microgravity which is another typical
      component in space. To confirm this, we must prepare centrifuge systems in an
      International Space Station (ISS). In addition, we must prepare many types of
      equipment for space experiments in an ISS, because we cannot use conventional
      equipment from our laboratories. Furthermore, the research for space radiation
      might give us valuable information about the birth and evolution of life on the
      Earth. We can also realize the importance of preventing the ozone layer from
      depletion by the use of exposure equipment to sunlight in an ISS. For these
      reasons, we desire to educate space researchers of the next generation based on
      the consideration of the preservation of the Earth from research about space
      radiation.

PMID- 12793724
TI  - Molecular targets in cellular response to ionizing radiation and implications in
      space radiation protection.
AB  - DNA repair systems and cell cycle checkpoints closely co-operate in the attempt
      of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA
      double-strand breaks (DSB) are considered as the most biologically important
      radiation-induced damage. Their spatial distribution and association with other
      types of damage depend on radiation quality. It is believed these features affect
      damage reparability, thus explaining the higher efficiency for cellular effects
      of densely ionizing radiation with respect to gamma-rays. DSB repair systems
      identified in mammalian cells are homologous recombination (HR), single-strand
      annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may
      participate in more than one of these repair systems. DNA damage also triggers
      biochemical signals activating checkpoints responsible for delay in cell cycle
      progression that allows more time for repair. Those at G1/S and S phases prevent
      replication of damaged DNA and those at G2/M phase prevent segregation of changed
      chromosomes. Individuals with lack or alterations of genes involved in DNA DSB
      repair and cell cycle checkpoints exhibit syndromes characterized by genome
      instability and predisposition to cancer. Information reviewed in this paper on
      the basic mechanisms of cellular response to ionizing radiation indicates their
      importance for a number of issues relevant to protection of astronauts from space
      radiation.

PMID- 12793725
TI  - Mutagenic effects of heavy charged particles.
AB  - Heavy charged particles constitute the most important radiation risk in space.
      Since mutations can give rise to cancer the investigation of their induction may
      be helpful for risk quantification. This paper describes experiments in a number
      of mammalian cells performed with a large range of linear energy transfer (LET).
      RBE values are always found to increase with LET up to about 100 keV/microm and
      are similar to those suggested by ICRP. Molecular analyses demonstrate that heavy
      charged particles not only lead to sometimes very large deletions but also to
      smaller changes which might represent point mutations. Recent evidence shows that
      repair phenomena play an important role in the processing of initial DNA lesions
      to mutagenic alterations.

PMID- 12793726
TI  - Measurement for the dose-rates of the cosmic-ray components on the ground.
AB  - In this study, we aimed to measure the directly ionizing component (muons and
      photons) and the indirectly ionizing component (neutrons) of the cosmic-ray
      spectra and evaluate their dose rate contribution to the total dose rate on a
      ground level in Japan. Measurements were carried out in Tohoku University, Japan,
      from October 2000. The pulse-height spectra of the cosmic-ray photons and muons
      were measured with a 12.7 cm diameter and 12.7 cm long NaI(Tl) scintillation
      detector. In order to measure energy spectra of cosmic-ray photons and muons,
      response functions of the detector to photons and muons were determined by the
      Monte Carlo simulation codes. The cosmic-ray photon dose was evaluated directly
      from the measured pulse-height spectrum by using the spectrum weight function,
      and the cosmic-ray muon dose was evaluated by converting the measured pulse
      height spectrum into deposited energy within the detector. The quantity of the
      cosmic-ray electrons is estimated to be very small and is not taken into account
      in this study. The cosmic-ray neutron spectrum and the neutron dose were measured
      by using a multi-moderator spectrometer (Bonner ball) and a rem counter. The
      measurements could finally give the annual absorbed dose in tissue of the cosmic
      ray muons of 315 microSv/y and annual ambient doses of the cosmic-ray photons and
      neutrons on the ground in Japan of 55 microSv/y and 31 microSv/y, respectively.

PMID- 12793727
TI  - Model predictions and visualization of the particle flux on the surface of Mars.
AB  - Model calculations of the particle flux on the surface of Mars due to the
      Galactic Cosmic Rays (GCR) can provide guidance on radiobiological research and
      shielding design studies in support of Mars exploration science objectives.
      Particle flux calculations for protons, helium ions, and heavy ions are reported
      for solar minimum and solar maximum conditions. These flux calculations include a
      description of the altitude variations on the Martian surface using the data
      obtained by the Mars Global Surveyor (MGS) mission with its Mars Orbiter Laser
      Altimeter (MOLA) instrument. These particle flux calculations are then used to
      estimate the average particle hits per cell at various organ depths of a human
      body in a conceptual shelter vehicle. The estimated particle hits by protons for
      an average location at skin depth on the Martian surface are about 10 to 100
      particle-hits/cell/year and the particle hits by heavy ions are estimated to be
      0.001 to 0.01 particle-hits/cell/year.

PMID- 12793728
TI  - Lunar lava tube radiation safety analysis.
AB  - For many years it has been suggested that lava tubes on the Moon could provide an
      ideal location for a manned lunar base, by providing shelter from various natural
      hazards, such as cosmic radiation, meteorites, micrometeoroids, and impact crater
      ejecta, and also providing a natural environmental control, with a nearly
      constant temperature, unlike that of the lunar surface showing extreme variation
      in its diurnal cycle. An analysis of radiation safety issues on lunar lava tubes
      has been performed by considering radiation from galactic cosmic rays (GCR) and
      Solar Particle Events (SPE) interacting with the lunar surface, modeled as a
      regolith layer and rock. The chemical composition has been chosen as typical of
      the lunar regions where the largest number of lava tube candidates are found.
      Particles have been transported all through the regolith and the rock, and
      received particles flux and doses have been calculated. The radiation safety of
      lunar lava tubes environments has been demonstrated.

PMID- 12793730
TI  - Activities of the Japanese space weather forecast center at Communications
      Research Laboratory.
AB  - The International Space Environment Service (ISES) is an international
      organization for space weather forecasts and belongs to the International Union
      of Radio Science (URSI). There are eleven ISES forecast centers in the world, and
      Communications Research Laboratory (CRL) runs the Japanese one. We make forecasts
      on the space environment and deliver them over the phones and through the
      Internet. Our forecasts could be useful for human activities in space. Currently
      solar activity is near maximum phase of the solar cycle 23. We report the several
      large disturbances of space environment occurred in 2001, during which low
      latitude auroras were observed several times in Japan.

PMID- 12793731
TI  - Modeling the response of thermoluminescence detectors exposed to low- and high
      LET radiation fields.
AB  - Lithium fluoride thermoluminescence (TL) detectors, with different Li composition
      (Li-6 and Li-7) and various activators (LiF:Mg,Ti, LiF:Mg,Cu,P), are widely used
      for dosimetry in space. The primary radiation field in space is composed of fast
      electrons, protons and heavy charged particles (HCP). By its interaction with the
      structures of the spacecraft, this field may be modified inside the crew cabin.
      Therefore, calibration of TL detectors against a dose of gamma-rays is not
      sufficient for relating the TL readout to absorbed dose or to quantities relevant
      in radiation protection, without suitable correction. We introduce and calculate
      the detection efficiency, eta, relative to gamma-ray dose, of lithium fluoride
      detectors after proton and heavy charged particle (HCP) irradiation. We calculate
      eta for MCP-N (LiF:Mg,Cu,P) and for MTS-N (LiF:Mg,Ti) using microdosimetric
      models. The microdosimetric distributions used in these models (for HCP of
      charges between Z=1 to Z=8 and in the energy range between 0.3 MeV/amu and 20
      MeV/amu) are calculated using an analytical model, based on the results of Monte
      Carlo simulated charged particle tracks using the MOCA-14 code. The ratio etaMCP
      N/etaMTS-N for protons of stopping power (in water) below 10 keV/microm lies in
      the range between 0.65 and 1.0 and for HCP with Z>1--between 0.3 and 0.6. The
      stopping power of the particle is found not to be a unique parameter to scale the
      response of TL detectors. The combination of response of LiF:Mg,Cu,P and
      LiF:Mg,Cu,P detectors can be more suitable for a dose correction in space
      radiation fields.

PMID- 12793729
TI  - The Sileye-3/Alteino experiment for the study of light flashes, radiation
      environment and astronaut brain activity on board the International Space
      Station.
AB  - In this work we describe the instrument Sileye-3/Alteino, placed on board the
      International Space Station in April 2002. The instrument is constituted by an
      Electroencephalograph and a cosmic ray silicon detector. The scientific aims
      include the investigation of the Light Flash phenomenon, the measurement of the
      radiation environment and the nuclear abundance inside the ISS and the study of
      astronaut brain activity in space when subject to cosmic rays.

PMID- 12793732
TI  - A simplified system for reading time-resolved photoluminescence.
AB  - A simplified system for measuring time-resolved photoluminescence (PL) induced by
      UV laser pulses (lambda = 337 nm) is designed by a combination of a commercial PL
      reader and a digital oscilloscope. Using this system, PL emissions after pulsed
      UV excitation from a chip of sapphire (Al2O3) are successfully measured with
      intervals of 10 ns. It is thus expected that this system will be conveniently
      used for searching new PL materials that would be more suitable for space
      radiation dosimetry.

PMID- 12793733
TI  - Thermoluminescence in sintered CaF2:Tb.
AB  - In order to observe and estimate the dose of ultraviolet (UV) radiation, the
      thermoluminescence (TL) of sintered CaF2 doped with Tb4O7 and Sm2O3 was studied.
      A several kind of lanthanides elements are doped in pure CaF2 powder crystals and
      properties of the TL to UV radiation were observed. The TL intensity from CaF2:Tb
      was the highest among the samples doped other lanthanide elements. The TL
      emission may be due to the recombination reaction; Tb2+ + hole-->Tb3+*-->Tb3+ +
      hv. The TL peaks are observed at about 353 K, 378 K and 458 K. It was found that
      the 378 K TL peak intensity of CaF2:Tb became strong by addition of Sm2O3. The
      378 K TL peak may also be suitable for use as a dosimeter.

PMID- 12793734
TI  - Possible application of an imaging plate to space radiation dosimetry.
AB  - Fading correction plays an important role in the application of commercially
      available BaBrF:Eu2+ phosphors: imaging plates (IP) to dosimetry. We successfully
      determined a fading correction equation, which is a function of elapsed time and
      absolute temperature, as the sum of several exponentially decaying components
      having different half-lives. In this work, a new method was developed to
      eliminate a short half-life component by annealing the IP and estimating the
      radiation dose with the long half-life components. Annealing decreases the effect
      of fading on the estimated dose, however, it also causes the loss of photo
      stimulated luminescence (PSL). Considering an IP as an integral detector for a
      specific period of up to one month, the practically optimum conditions for
      quantitative measurement with two types of IP (BAS-TR and BAS-MS) were evaluated
      by using the fading correction equation, which was obtained after irradiation
      with a 244Cm source as the alpha-ray source having a specific radioactivity of
      1,638.5 Bq/cm2 including beta and gamma-ray (alpha energy of 5.763 and 5.805
      MeV). Annealing at 80 degrees C for 24 hours after irradiation for one month
      using BAS-MS should minimize the effect of the elapsed time, resulting in
      sufficient sensitivity. The results demonstrate new possibilities for radiation
      dosimetry offered by the use of an IP.

PMID- 12793735
TI  - LET distributions measured at the CERF facility with the RRMD-III.
AB  - The LET distributions in front of the 80 cm-thick concrete side shield at the
      CERF facility were measured with a Si detector telescope (RRMD-III) covered with
      and without a 1 cm-thick acrylic plate. In these measurements, a slight
      difference between the LET distributions was seen as a result of recoil protons
      and/or carbon particles by neutrons. Also, the LET distributions are compared
      with the micro-dosimetric spectrum (i.e., lineal energy distribution) measured
      with a cylindrical TEPC under the same conditions.

PMID- 12793736
TI  - Intercomparison of radiation instruments for cosmic-ray with heavy ion beams at
      NIRS (ICCHIBAN project).
AB  - The first InterComparison for Cosmic-ray with Heavy Ion Beams At NIRS (ICCHIBAN)
      project is an ongoing, international collaboration organized at the National
      Institute of Radiological Sciences (NIRS), Japan, for the purpose of
      characterizing and comparing at a controlled, ground-based heavy ion facility the
      radiation response of instruments used aboard piloted spacecraft for crew and
      area dosimetry. We present preliminary results from the first set of ICCHIBAN
      exposures made at HIMAC heavy ion accelerator in February 2002. The initial
      series of exposures (1st ICCHIBAN run) was designed to establish the response of
      active detectors to two well-characterized heavy ion beams; 400 MeV/nucleon 12C
      and 400 MeV/nucleon 56Fe. These beams are representative in charge and energy of
      two of the most significant heavy ion components present in the galactic cosmic
      radiation spectrum. The properties of the incident beam, including intensity,
      profile, charge and total energy, were characterized using several different
      detector systems, including silicon detectors, CR-39 plastic nuclear track
      detectors and plastic scintillation counters. Once the response of each detector
      to heavy ion beams of known composition has been measured, results from on-orbit
      measurements made by the different instruments can be more meaningfully compared.
      We conclude by discussing plans for future ICCHIBAN runs, including next 2nd
      ICCHIBAN run for passive detectors in early summer 2002.

PMID- 12793737
TI  - Advances in space radiation shielding codes.
AB  - Early space radiation shield code development relied on Monte Carlo methods and
      made important contributions to the space program. Monte Carlo methods have
      resorted to restricted one-dimensional problems leading to imperfect
      representation of appropriate boundary conditions. Even so, intensive
      computational requirements resulted and shield evaluation was made near the end
      of the design process. Resolving shielding issues usually had a negative impact
      on the design. Improved spacecraft shield design requires early entry of
      radiation constraints into the design process to maximize performance and
      minimize costs. As a result, we have been investigating high-speed computational
      procedures to allow shield analysis from the preliminary concept to the final
      design. For the last few decades, we have pursued deterministic solutions of the
      Boltzmann equation allowing field mapping within the International Space Station
      (ISS) in tens of minutes using standard Finite Element Method (FEM) geometry
      common to engineering design methods. A single ray trace in such geometry
      requires 14 milliseconds and limits application of Monte Carlo methods to such
      engineering models. A potential means of improving the Monte Carlo efficiency in
      coupling to spacecraft geometry is given.

PMID- 12793738
TI  - Secondary particle production in tissue-like and shielding materials for light
      and heavy ions calculated with the Monte-Carlo code SHIELD-HIT.
AB  - The Monte Carlo code SHIELD has been modified into a version named SHIELD-HIT
      which extends the transport of hadron cascades in shielding materials to that of
      ions in tissue-like materials, and includes ion energy-loss straggling, multiple
      scattering, track-length calculations and production of secondary particles,
      which includes all generations, for ion interactions with the media. Calculations
      using SHIELD-HIT have been performed for 1H, 12C and 26Fe ions with energies up
      to 1000 MeV/u transported through water, soft tissue and aluminium. These have
      been validated by comparing Monte Carlo results with experimental data and
      results from other Monte Carlo codes for ion transport. Good agreement has been
      found for depth-dose distributions of protons and 12C ions in water up to depths
      well beyond the Bragg peak, where nuclear fragmentation effects dominate and for
      the production of secondary particles at different depths. Detailed track-length
      fluence spectra of secondary particles have been calculated for various
      combinations of projectiles and targets of interest for space radiation and
      radiotherapy applications. The secondary particle spectra in water from carbon
      ions have been used for calculations of stopping-power ratios for ionization
      chamber dosimetry, confirming the values recommended by the IAEA Code of Practice
      for radiotherapy dosimetry with heavy ions.

PMID- 12793739
TI  - Modelling the influence of shielding on physical and biological organ doses.
AB  - Distributions of "physical" and "biological" dose in different organs were
      calculated by coupling the FLUKA MC transport code with a geometrical human
      phantom inserted into a shielding box of variable shape, thickness and material.
      While the expression "physical dose" refers to the amount of deposited energy per
      unit mass (in Gy), "biological dose" was modelled with "Complex Lesions" (CL),
      clustered DNA strand breaks calculated in a previous work based on "event-by
      event" track-structure simulations. The yields of complex lesions per cell and
      per unit dose were calculated for different radiation types and energies, and
      integrated into a version of FLUKA modified for this purpose, allowing us to
      estimate the effects of mixed fields. As an initial test simulation, the phantom
      was inserted into an aluminium parallelepiped and was isotropically irradiated
      with 500 MeV protons. Dose distributions were calculated for different values of
      the shielding thickness. The results were found to be organ-dependent. In most
      organs, with increasing shielding thickness the contribution of primary protons
      showed an initial flat region followed by a gradual decrease, whereas secondary
      particles showed an initial increase followed by a decrease at large thickness
      values. Secondary particles were found to provide a substantial contribution,
      especially to the biological dose. In particular, the decrease of their
      contribution occurred at larger depths than for primary protons. In addition,
      their contribution to biological dose was generally greater than that of primary
      protons.

PMID- 12793740
TI  - Implementation of Gy-Eq for deterministic effects limitation in shield design.
AB  - The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in
      estimation of deterministic effects in space shielding and operations. The NCRP's
      RBE for neutrons is left ambiguous and not fully defined. In the present report
      we will suggest a complete definition of neutron RBE consistent with the NCRP
      recommendations and evaluate attenuation properties of deterministic effects (Gy
      Eq) in comparison with other dosimetric quantities.

PMID- 12793741
TI  - Influence of the shielding on the induction of chromosomal aberrations in human
      lymphocytes exposed to high-energy iron ions.
AB  - Computer code calculations based on biophysical models are commonly used to
      evaluate the effectiveness of shielding in reducing the biological damage caused
      by cosmic radiation in space flights. Biological measurements are urgently needed
      to benchmark the codes. We have measured the induction of chromosomal aberrations
      in human peripheral blood lymphocytes exposed in vitro to 56Fe-ion beams
      accelerated at the HIMAC synchrotron in Chiba. Isolated lymphocytes were exposed
      to the 500 MeV/n iron beam (dose range 0.1-1 Gy) after traversal of 0 to 8 g/cm2
      of either PMMA (lucite, a common plastic material) or aluminum. Three PMMA shield
      thickness and one Al shield thickness were used. For comparison, cells were
      exposed to 200 MeV/n iron ions and to X-rays. Chromosomes were prematurely
      condensed by a phosphatase inhibitor (calyculin A) to avoid cell-cycle selection
      produced by the exposure to high-LET heavy ion beams. Aberrations were scored in
      chromosomes 1, 2, and 4 following fluorescence in situ hybridization. The yield
      of chromosomal aberrations per unit dose at the sample position was poorly
      dependent on the shield thickness and material. However, the yield of aberrations
      per unit ion incident on the shield was increased by the shielding. This increase
      is associated to the increased dose-rate measured behind the shield as compared
      to the direct beam. These preliminary results prove that shielding can increase
      the effectiveness of heavy ions, and the damage is dependent upon shield
      thickness and material.

PMID- 12793742
TI  - Fluence-based and microdosimetric event-based methods for radiation protection in
      space.
AB  - The National Council on Radiation Protection and Measurements (NCRP) has recently
      published a report (Report #137) that discusses various aspects of the concepts
      used in radiation protection and the difficulties in measuring the radiation
      environment in spacecraft for the estimation of radiation risk to space
      travelers. Two novel dosimetric methodologies, fluence-based and microdosimetric
      event-based methods, are discussed and evaluated, along with the more
      conventional quality factor/LET method. It was concluded that for the present,
      any reason to switch to a new methodology is not compelling. It is suggested that
      because of certain drawbacks in the presently-used conventional method, these
      alternative methodologies should be kept in mind. As new data become available
      and dosimetric techniques become more refined, the question should be revisited
      and that in the future, significant improvement might be realized. In addition,
      such concepts as equivalent dose and organ dose equivalent are discussed and
      various problems regarding the measurement/estimation of these quantities are
      presented.

PMID- 12793743
TI  - Visualization of particle flux in the human body on the surface of Mars.
AB  - For a given galactic cosmic ray (GCR) environment, information on the particle
      flux of protons, alpha particles, and heavy ions, that varies with respect to the
      topographical altitude on the Martian surface, are needed for planning
      exploration missions to Mars. The Mars Global Surveyor (MGS) mission with its
      Mars Orbiter Laser Altimeter (MOLA) instrument has been providing precise
      topographical surface map of the Mars. With this topographical data, the particle
      flux at the Martian surface level through the CO2 atmospheric shielding for solar
      minimum and solar maximum conditions are calculated. These particle flux
      calculations are then transported first through an anticipated shielding of a
      conceptual shelter with several water equivalent shield values (up to 50 g/cm2 of
      water in steps of 5 g/cm2) considered to represent a surface habitat, and then
      into the human body. Model calculations are accomplished utilizing the HZETRN,
      QMSFRG, and SUM-MARS codes. Particle flux calculations for 12 different locations
      in the human body were considered from skin depth to the internal organs
      including the blood-forming organs (BFO). Visualization of particle flux in the
      human body at different altitudes on the Martian surface behind a known shielding
      is anticipated to provide guidance for assessing radiation environment risk on
      the Martian surface for future human missions.

PMID- 12793744
TI  - Space radiation protection: comparison of effective dose to bone marrow dose
      equivalent.
AB  - In many instances, bone marrow dose equivalents averaged over the entire body
      have been used as a surrogate for whole-body dose equivalents in space radiation
      protection studies. However, career radiation limits for space missions are
      expressed as effective doses. This study compares calculations of effective doses
      to average bone marrow dose equivalents for several large solar particle events
      (SPEs) and annual galactic cosmic ray (GCR) spectra, in order to examine the
      suitability of substituting bone marrow dose equivalents for effective doses.
      Organ dose equivalents are computed for all radiosensitive organs listed in NCRP
      Report 116 using the BRYNTRN and HZETRN space radiation transport codes and the
      Computerized Anatomical Man (CAM) model. These organ dose equivalents are then
      weighted with the appropriate tissue weighting factors to obtain effective doses.
      Various thicknesses of aluminum shielding, which are representative of nominal
      spacecraft and SPE storm shelter configurations, are used in the analyses. For
      all SPE configurations, the average bone marrow dose equivalent is considerably
      less than the calculated effective dose. For comparisons of the GCR, there is
      less than a ten percent difference between the two methods. In all cases, the
      gonads made up the largest percentage of the effective dose.

PMID- 12793746
TI  - Detection of DNA damage induced by space radiation in Mir and space shuttle.
AB  - Although physical monitoring of space radiation has been accomplished, we aim to
      measure exact DNA damage as caused by space radiation. If DNA damage is caused by
      space radiation, we can detect DNA damage dependent on the length of the space
      flight periods by using post-labeling methods. To detect DNA damage caused by
      space radiation, we placed fixed human cervical carcinoma (HeLa) cells in the
      Russian Mir space station for 40 days and in an American space shuttle for 9
      days. After landing, we labeled space-radiation-induced DNA strand breaks by
      enzymatic incorporation of [3H]-dATP with terminal deoxyribo-nucleotidyl
      transferase (TdT). We detected DNA damage as many grains on fixed silver emulsion
      resulting from beta-rays emitted from 3H-atoms in the nuclei of the cells placed
      in the Mir-station (J/Mir mission, STS-89), but detected hardly any in the ground
      control sample. In the space shuttle samples (S/MM-8), the number of cells having
      many grains was lower than that in the J/Mir mission samples. These results
      suggest that DNA damage is caused by space radiation and that it is dependent on
      the length of the space flight.

PMID- 12793745
TI  - Analysis of complex-type chromosome exchanges in astronauts' lymphocytes after
      space flight as a biomarker of high-LET exposure.
AB  - High-LET radiation is more efficient in producing complex-type chromosome
      exchanges than sparsely ionizing radiation, and this can potentially be used as a
      biomarker of radiation quality. To investigate if complex chromosome exchanges
      are induced by the high-LET component of space radiation exposure, damage was
      assessed in astronauts' blood lymphocytes before and after long duration missions
      of 3-4 months. The frequency of simple translocations increased significantly for
      most of the crewmembers studied. However, there were few complex exchanges
      detected and only one crewmember had a significant increase after flight. It has
      been suggested that the yield of complex chromosome damage could be
      underestimated when analyzing metaphase cells collected at one time point after
      irradiation, and analysis of chemically-induced PCC may be more accurate since
      problems with complicated cell-cycle delays are avoided. However, in this case
      the yields of chromosome damage were similar for metaphase and PCC analysis of
      astronauts' lymphocytes. It appears that the use of complex-type exchanges as
      biomarker of radiation quality in vivo after low-dose chronic exposure in mixed
      radiation fields is hampered by statistical uncertainties.

PMID- 12793747
TI  - Mutation frequency of plasmid DNA and Escherichia coli following long-term space
      flight on Mir.
AB  - To elucidate the biological influence of space radiation, we studied the effects
      of long-term space flight on mutation of the bacterial ribosomal protein L gene
      (rpsL). We prepared dried samples of plasmid DNA and repair-deficient and wild
      type cells of Escherichia (E.) coli. After a 40-day space flight on board the
      Russian space station Mir, the mutation frequencies of the rpsL gene were
      estimated by transformation of E. coli and by assessment of conversion of rpsL
      wild type phenotype (SmS) to its mutant phenotype (SmR). The experimental
      findings indicate that mutation frequencies of space samples were not
      significantly different from those of ground control samples in plasmid DNA and
      both E. coli strains. It may suggest that space radiation did not influence
      mutation frequency.

PMID- 12793748
TI  - Effect of space flight on the frequency of micronuclei and expression of stress
      responsive proteins in cultured mammalian cells.
AB  - Results of past space experiments suggest that the biological effect of space
      radiation could be enhanced under microgravity in some cases, especially in
      insects. To examine if such a synergistic effect of radiation and microgravity
      also exists in human cells, frequencies of chromosome instability and cellular
      levels of several stress-responsive proteins were analyzed in cultured human and
      rodent cells after space flight. Human (MCF7 and AT2KY), mouse (m5S) and hamster
      (SHE) cell lines were loaded on the Space Shuttle Discovery (STS-95 mission) and
      grown during a 9-day mission. After landing, the micronuclei resulting from
      abnormal nuclear division and accumulation of stress-responsive proteins such as
      p53 and mitogen-activated protein kinases (MAPKs), which are involved in
      radiation-induced signal transduction cascades, were analyzed. The frequencies of
      micronuclei in all the four mammalian cell strains tested were not significantly
      different between flight and ground control samples. Also, the cellular amounts
      of p53, p21 (WAF1/SDI1/CIP1) and activated (phosphorylated) forms of three
      distinct MAPKs in MCF7 and m5S cells of flight samples were similar to those of
      ground control samples. These results indicated that any effect of space
      radiation, microgravity, or combination of both were not detectable, at least
      under the present experimental conditions.

PMID- 12793749
TI  - Clustered DNA damages induced in human hematopoietic cells by low doses of
      ionizing radiation.
AB  - Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites
      and strand breaks--on opposing strands within a few helical turns. Such damages
      have been postulated to be difficult to repair, as are double strand breaks (one
      type of cluster). We have shown that low doses of low and high linear energy
      transfer (LET) radiation induce such damage clusters in human cells. In human
      cells, DSB are about 30% of the total of complex damages, and the levels of DSBs
      and oxidized pyrimidine clusters are similar. The dose responses for cluster
      induction in cells can be described by a linear relationship, implying that even
      low doses of ionizing radiation can produce clustered damages. Studies are in
      progress to determine whether clusters can be produced by mechanisms other than
      ionizing radiation, as well as the levels of various cluster types formed by low
      and high LET radiation.

PMID- 12793750
TI  - Detection of DNA damage in individual cells induced by heavy-ion irradiation with
      an non-denaturing comet assay.
AB  - Investigating the biological effects of high-LET heavy-ion irradiation at low
      fluence is important to evaluate the risk of radiation in space. It is especially
      necessary to detect radiation damage induced by a precise number of heavy ions in
      individual cells. We thus compared the number of ions traversing a cell and the
      DNA damage produced by ion hits. We applied a comet assay to measure the DNA
      damage in individual cells. Cells attached on ion-track detector (CR-39) were
      irradiated with 17.3 MeV/u 12C, 15.7 MeV/u, 10.4 MeV/u 20Ne ion and 7.2 MeV/u
      40Ar beams at TIARA, JAERI-Takasaki. After irradiation, CR-39 was covered with 1%
      agarose. The agarose was allowed to solidify on a glass slide, and then the
      electrophoresis was performed. Afterward, the CR-39 was taken off the glass
      slide. The agarose gel on the CR-39 was stained with ethidium bromide and the
      opposite side of the CR-39 was etched with a KOH-ethanol solution at 37 degrees
      C. We observed that heavy ions with higher LET values induced heavier DNA damage,
      even with the same number of ion hits within the irradiated cells. The result
      indicated that the amount of DNA damage induced by one particle depended on the
      LET value of the heavy ions.

PMID- 12793752
TI  - Sensitive detection of LOH events in a human cell line after C-ion beam exposure.
AB  - A molecular analysis of the loss of heterozygosity (LOH) events in human cells
      after low-dose heavy-ion exposure could contribute to the sensitive detection of
      the genetic influences caused by high-LET radiation. We exposed human
      lymphoblastoid TK6-20C cells to 10 cGy of an accelerated C-ion (22 keV/microm)
      beam, and observed a 3.1-fold increase in the mutation frequency (MF) at the
      heterozygous thymidine kinase (TK) locus over the background level. This increase
      was due to the induction of TK mutants exhibiting hemizygous-type LOH.
      Surprisingly, the frequency of type-2 hemizygous LOHs (interstitial deletions)
      was about 23-fold, induced over the background level, and the LOH extent patterns
      of this type 2 induced after the irradiation were clearly different from that of
      the spontaneous background.. Since hemizygous-type LOH mutants are considered to
      be the result of the end-joining repair of DNA double-strand breaks (DSB), C-ions
      may more efficiently induce DSBs than X-rays in this low-dose region. In
      addition, an enhanced misrepair of C-ion-induced DSBs might also account for the
      induction of radiation-specific hemizygous-type LOH.

PMID- 12793751
TI  - Chlorophyll-deficient mutants of rice demonstrated the deletion of a DNA fragment
      by heavy-ion irradiation.
AB  - Heavy-ion irradiation is a new method of mutation breeding to produce new
      cultivars. We established the application of this method in rice plants to obtain
      mutants. Rice seeds were irradiated by C or Ne ions (135MeV/u) with a LET (linear
      energy transfer) of 22.7 or 64.2 keV/microm, respectively. Chlorophyll-deficient
      mutants (CDM) segregated in M2 progeny were albino, pale-green, yellow or striped
      leave phenotypes. The highest rate of CDM with C-ion irradiation, 7.31%, was
      obtained at 40 Gy among the doses examined. Ne-ion irradiation gave the highest
      rate, 11.6%, at 20 Gy. We used the RLGS (Restriction Landmark Genomic Scanning)
      method to analyze DNA deletion in an albino mutant genome. Not I-landmark RLGS
      profiles detected about 2000 spots in rice. We found that one of the polymorphic
      spots was strongly linked to the albino phenotypic mutant derived from deleting
      of a DNA fragment, and demonstrated the high ability to detect of polymorphic
      regions by the RLGS method.

PMID- 12793753
TI  - Induction of chromatin damage and distribution of isochromatid breaks in human
      fibroblast cells exposed to heavy ions.
AB  - The frequency of chromatid breaks and the distribution of isochromatid breaks
      were measured in G2-phase normal human fibroblasts prematurely condensed a short
      time after exposure to low- or high-LET radiations. The average number of
      isochromatid breaks from a single particle traversal increased with increasing
      LET values, while the average number of chromatid-type breaks appeared to reach a
      plateau. The distribution of isochromatid breaks after high-LET iron particles
      exposure was overdispersed compared to gamma-rays, indicating that a single iron
      particle traversal through a cell nucleus can produce multiple isochromatid
      breaks.

PMID- 12793754
TI  - Relationship between aberration yield and mitotic delay in human lymphocytes
      exposed to 200 MeV/u Fe-ions or X-rays.
AB  - The time-course of Fe-ion (200 MeV/u, 440 keV/microm) and X-ray induced
      chromosomal damage was investigated in human lymphocytes. After cells were
      exposed in G0 and stimulated to grow, aberrations were measured in first-cycle
      metaphases harvested 48, 60 and 72 h post-irradiation. Additionally, lesions were
      analysed in G2 and mitotic (M) cells collected at 48 h using calyculin A-induced
      premature chromosome condensation (PCC). Following X-irradiation, similar
      aberration yields were found in all of the samples scored. In contrast, after Fe
      ion exposure a drastic increase in the aberration frequency with sampling time
      was observed, i.e. cells arriving late at the first mitosis carried more
      aberrations than those arriving at earlier times. The PCC data indicate that the
      delayed entry of heavily damaged cells into mitosis observed after Fe-ion
      irradiation resulted from a prolonged arrest in G2. Altogether these experiments
      provide further evidence that in the case of high-LET exposure cell-cycle delays
      of severely damaged cells have to be taken into account for any meaningful
      quantification of chromosomal damage and, consequently, for an accurate estimate
      of the RBE.

PMID- 12793755
TI  - Analysis of unrejoined chromosomal breakage in human fibroblast cells exposed to
      low- and high-LET radiation.
AB  - Reported studies of DNA breakage induced by radiation of various qualities have
      generally shown a higher fraction of unrejoined residual breaks after high-LET
      exposure. This observation is supported by the argument that high-LET radiation
      induced DNA breaks that are more complex in nature and, thus, less likely to be
      repaired. In most cases the doses used in these studies were very high. We have
      studied unrejoined chromosome breaks by analyzing chromosome aberrations using a
      fluorescence in situ hybridization (FISH) technique with a combination of whole
      chromosome specific probes and probes specific for the telomere region of the
      chromosomes. Confluent human fibroblast cells (AG1522) were irradiated with gamma
      rays, 490 MeV/nucleon Si, or with Fe ions at either 200 and 500 MeV/nucleon, and
      were allowed to repair at 37 degrees C for 24 hours after exposure. A chemically
      induced premature chromosome condensation (PCC) technique was used to condense
      chromosomes in the G2 phase of the cell cycle. Results showed that the frequency
      of unrejoined chromosome breaks was higher after high-LET radiation, and the
      ratio of unrejoined to misrejoined chromosome breaks increased steadily with LET
      up a peak value at 440 keV/microm.

PMID- 12793756
TI  - Heritable non-lethal damage to cultured human cells irradiated with heavy ions.
AB  - During interplanetary flights the nuclei of all of a crew member's cells could be
      traversed by at least one high-LET (Linear Energy Transfer) cosmic-ray particle.
      In mammalian cells irradiated in vitro about 1 in 10,000 of the surviving cells
      traversed by heavy particles is transformed to malignancy or mutated. What, if
      anything, happens to the remaining >99% of surviving cells? A retrospective
      analysis of archived data and samples from heavy-ion irradiation experiments with
      cultured human cells in vitro indicated that heavy ions caused a dose- and LET
      dependent reduction in growth rates of progeny of irradiated cells, based on
      colony-size distributions. The maximum action cross section for this effect is
      between 100 and 300 microm2, at least as large as the cell nuclear area and up to
      3 times the cross section for cell killing. Thus, heritable slow growth is the
      most prevalent effect of high-LET radiations on cultured animal cells, which may
      have implications for crew health during deep space travel. DISCLAIMER: The views
      expressed in this article are those of the author(s) and do not necessarily
      reflect the views or policies of the USEPA.

PMID- 12793757
TI  - Somatic mutation in larvae of the silkworm, Bombyx mori, induced by heavy ion
      irradiation to diapause eggs.
AB  - In order to investigate whether eggs of the black-striped strain (P(S)) of the
      silkworm, Bombyx mori, represent an appropriate model for estimating the
      biological effect of cosmic radiation, radiosensitivity of the eggs against X
      rays and heavy ion particles was examined as ground-based experiments. The
      exposure of diapause eggs to X-rays or heavy ion particles resulted in somatic
      mutations appearing as a white spot on the black integument during larval stage.
      Irradiation of non-diapause eggs with X-rays demonstrated a significant
      difference in frequency of the mutation between fractionated and single
      administration doses, but no difference was observed in diapause eggs. Incidence
      of the mutation as induced by carbon ion beams for 15-day old eggs was higher for
      eggs that had been kept at 15 degrees C than those kept at 25 degrees C. Neon
      beam irradiation of diapause eggs displayed dose- and linear energy transfer
      (LET)-dependent effects, causing a maximal rate of the mutation at 150
      keV/microm. These results confirm that B. mori eggs represent valid models for
      estimating the biological effects of cosmic radiation.

PMID- 12793758
TI  - Radiation-induced gene expression in the nematode Caenorhabditis elegans.
AB  - We used the nematode C. elegans to characterize the genotoxic and cytotoxic
      effects of ionizing radiation in a simple animal model emphasizing the unique
      effects of charged particle radiation. Here we demonstrate by RT-PCR differential
      display and whole genome microarray hybridization experiments that gamma rays,
      accelerated protons and iron ions at the same physical dose lead to unique
      transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential
      expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406
      were down-regulated and 90% were affected only by a single species of radiation.
      A novel statistical clustering technique identified the regulatory relationships
      between the radiation-modulated genes and showed that genes affected by each
      radiation species were associated with unique regulatory clusters. This suggests
      that independent homeostatic mechanisms are activated in response to radiation
      exposure as a function of track structure or ionization density.

PMID- 12793759
TI  - Micronuclei induced by low dose rate irradiation in early spermatids of p53 null
      and wild mice.
AB  - To obtain evidence of the dose-rate effect on induction of micronuclei in early
      spermatids, we observed frequencies in wild-type p53(+/+), heterozygous p53(+/-)
      and null p53(-/-) mice 14 days after gamma rays irradiation at a high (1,020
      mGy/min) or a low (1.2 mGy/min) dose-rate. A dose- and dose-rate-related increase
      in micronuclei was seen in early spermatids with no difference between the
      different p53 status. These data were found to be best fitted by a linear
      quadratic dose-response model at a high dose-rate, and by a linear dose-response
      model at a low dose-rate. The yields at 1.2 mGy/min were significantly lower than
      those at 1,020 mGy/min in the same manner, independent of p53 status. Testis
      weight declined significantly after 3 Gy irradiation, but did not depend on dose
      rates. In our other studies, we observed the complete elimination both of
      malformation in fetuses and CD3- 4+ mutant T-lymphocytes in p53(+/+) mice, but
      not in p53(-/-) mice after irradiation. This indicates that concerted DNA repair
      and p53-dependent apoptosis are likely to completely eliminate mutagenic damage
      from the irradiated tissues at low doses or dose-rates in teratogenesis and
      lymphocytes. In the germ cell, however, irradiation at 1.2 mGy/min was mutagenic,
      independent of p53 status.

PMID- 12793760
TI  - Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice.
AB  - When DNA is damaged by exposure to a small amount of radiation, it is repaired
      efficiently by innate mechanisms. However, if cellular damage is more extensive,
      DNA repair cannot be adequately completed. To clarify the role of the p53 gene in
      apoptotic tissue repair, the incidence of in-vivo radiation-induced somatic
      mutation was evaluated by measuring the T cell receptor (TCR) gene expression in
      p53(+/+) and p53(-/-) mice. After gamma-irradiation with 3 Gy, the TCR mutation
      frequency (MF) was higher in p53(+/+) mice than in the controls. However, when
      the mice were exposed to 3 Gy at a low dose rate, the TCR MF did not increase in
      the p53(+/+) mice, whereas it increased and remained elevated in p53(-/-) mice,
      which are unable to induce apoptosis. In p53(+/+) mice, the TCR MF peaked 9 days
      after gamma-irradiation with 3 Gy at a high dose rate, and then gradually
      decreased with a half-life of about 13 days. However, in p53(-/-) mice, the peak
      level of the TCR MF did not decline significantly with time. Hence, complete
      repair of mutagenic damage in irradiated tissues requires the integration of DNA
      repair and p53-dependent apoptotic tissue repair.

PMID- 12793761
TI  - Cytoskeletal and functional changes in bioreactor assembled thyroid tissue
      organoids exposed to gamma radiation.
AB  - Fischer rat thyroid cells were grown under low-shear stress in a bioreactor to a
      stage of organization composed of integrated follicles resembling small thyroid
      glands prior to exposure to 3 Gray-gamma radiation. Bioreactor tissues and
      controls (both irradiated and non-irradiated) were harvested at 24, 48, 96 and
      144 hours post-exposure. Tissue samples were fixed and fluorescently labeled for
      actin and microtubules. Tissues were assessed for changes in cytoskeletal
      components induced by radiation and quantified by laser scanning cytometry.
      ELISA's were used to quantify transforming growth factor-beta and thyroxin
      released from cells to the culture supernatant. Tissue architecture was disrupted
      by exposure to radiation with the structural organization of actin and loss of
      follicular content the most obviously affected. With time post-irradiation the
      actin appeared disordered and the levels of fluorescence associated with
      filamentous-actin and microtubules cycled in the tissue analogs, but not in the
      flask-grown cultures. Active transforming growth factor-beta was higher in
      supernatants from the irradiated bioreactor tissue. Thyroxin release paralleled
      cell survival in the bioreactors and control cultures. Thus, the engineered
      tissue responses to radiation differed from those of conventional tissue culture
      making it a potentially better mimic of the in vivo situation.

PMID- 12793762
TI  - Apolipoprotein E expression and behavioral toxicity of high charge, high energy
      (HZE) particle radiation.
AB  - Apolipoprotein E (apoE) is a lipid binding protein that plays an important role
      in tissue repair following brain injury. In the present studies, we have
      investigated whether apoE affects the behavioral toxicity of high charge, high
      energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice
      and sixteen genetically matched wild-type (WT) C57BL mice were used in this
      experiment. Half of the KO and half of the WT animals were irradiated with 600
      MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor
      coordination and stamina (Rotarod test), exploratory behavior (open field test),
      and spatial working and reference memory (Morris water maze) was assessed.
      ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO
      and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation
      effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST:
      Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after
      irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE:
      Radiation adversely affected spatial working memory in the KO mice, but had no
      discernible effect in the WT mice as assessed 180 d after irradiation. In
      contrast, irradiated WT mice showed marked impairment of spatial reference memory
      in comparison to non-irradiated mice, while no effect of radiation was observed
      in KO mice. CONCLUSIONS: These studies show that apoE expression influences the
      behavioral toxicity of HZE particle radiation and suggest that apoE plays a role
      in the repair/recovery from radiation injury of the CNS. ApoE deficiency may
      exacerbate the previously reported effects of HZE particle radiation in
      accelerating the brain aging process.

PMID- 12793763
TI  - Effects of exposure to 56Fe particles or protons on fixed-ratio operant
      responding in rats.
AB  - On long-duration trips outside of the magnetosphere, astronauts will be exposed
      to protons and to heavy particles which can affect their performance of required
      tasks. It is essential to determine the range of behaviors that might be affected
      by exposure to these types of radiation in order to understand the nature of
      behavioral deficits and to develop effective countermeasures. The present
      experiment examined the ability of rats to make an operant response following
      exposure to protons (250 MeV, 4 Gy) or 56Fe particles (1 GeV/n, 1 or 2 Gy).
      Following irradiation, rats were trained to press a lever in order to obtain food
      reinforcement. They were then placed on an ascending fixed-ratio schedule from FR
      1 (each lever press rewarded with a food pellet) through FR-35 (35 lever presses
      required for 1 food pellet). Rats exposed to 4 Gy of protons or 1 Gy of 56Fe
      particles responded similarly to controls, increasing their rate of responding as
      the ratio increased. However, rats exposed to 2 Gy of 56Fe particles failed to
      increase their rate of responding at ratios greater than FR-20, indicating that
      rats exposed to 2 Gy of 56Fe particles cannot respond appropriately to increasing
      work requirements.

PMID- 12793764
TI  - The action of a dietary retinoid on gene expression and cancer induction in
      electron-irradiated rat skin.
AB  - Current models of radiation carcinogenesis generally assume that the DNA is
      damaged in a variety of ways by the radiation and that subsequent cell divisions
      contribute to the conversion of the damage to heritable mutations. Cancer may
      seem complex and intractable, but its complexity provides multiple opportunities
      for preventive interventions. Mitotic inhibitors are among the strongest cancer
      preventive agents, not only slowing the growth rate of preneoplasias but also
      increasing the fidelity of DNA repair processes. Ionizing radiation, including
      electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have
      shown potent cancer preventive activity in the same system. A non-toxic dietary
      dose of retinyl acetate altered gene expression levels 24 hours after electron
      irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array,
      the radiation significantly (5 fold or higher) altered 188, while the retinoid
      altered 231, including 16 radiation-altered genes that were reversely altered.
      While radiation strongly affected the expression of stress response,
      immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly
      affected proliferation-related genes, including some significant reversals, such
      as, keratin 14, retinol binding protein, and calcium binding proteins. These
      results point to reversal of proliferation-relevant genes as a likely basis for
      the anti-radiogenic effects of dietary retinyl acetate.

PMID- 12793765
TI  - Preventive effects of running exercise on bones in heavy ion particle irradiated
      rats.
AB  - We examined the effects of running exercise on preventing decreases in bone
      mineral and tissue volume after heavy ion particle irradiation in rats. Male
      Wistar rats experienced whole-body irradiation by heavy ion particle beam (C-290
      MeV) at doses of 0.5, 1.0, and 5.0 Gy and were divided into voluntary running
      groups and control groups. Rats in the running groups ran on the treadmill 15
      m/min, 90 min/day for 35 days after exposure. At the end of the experiment, a
      tibia was obtained from each rat for measurement of bone mineral density (BMD)
      and cross-sectional area, strength strain index, and bone histomorphometric
      analysis. The weights of muscles and concentration of serum calcium were
      measured. Total BMD and trabecular BMD in the metaphysis and cortical BMD of the
      diaphysis of tibia in the running groups increased. Bone volume and trabecular
      thickness increased while trabecular separation decreased in the running groups
      compared to those in the control groups at respective doses. However, the osteoid
      surface and eroded surface varied in the running groups compared to those of the
      respective corresponding groups. The dynamic parameters such as mineralizing
      surface, mineral apposition rate, and bone formation rate in the running groups
      were varied, probably due to the differences in radiation-induced sensitivities
      of bones following radiation exposure. The overall results suggest that running
      exercise might have a beneficial effect on preventing bone mineral loss and
      changes in bone structure induced by space radiation, but it is necessary to
      examine the optimal conditions of running exercise response to doses.

PMID- 12793766
TI  - New strategies for the prevention of radiation injury: possible implications for
      countering radiation hazards of long-term space travel.
AB  - New strategies for the prevention of radiation injuries are currently being
      explored with the ultimate aim of developing globally radioprotective, nontoxic
      pharmacologics. The prophylactic treatments under review encompass such diverse
      pharmacologic classes as novel immunomodulators, nutritional antioxidants, and
      cytokines. An immunomodulator that shows promise is 5-androstenediol (AED), a
      well-tolerated, long-acting androstene steroid with broad-spectrum
      radioprotective attributes that include not only protection against acute tissue
      injury, but also reduced susceptibility to infectious agents, as well as reduced
      rates of neoplastic transformation. Other potentially useful radioprotectants
      currently under study include the nutraceutical vitamin E and analogs, a
      chemically-engineered cytokine, interleukin-1beta, and a sustained-release
      formulation of an aminothiol, amifostine. Results suggest that a new paradigm is
      evolving for the prophylaxes of radiation injuries, based on use of newly
      identified, nontoxic, broad-spectrum prophylactic agents whose protective action
      may be leveraged by subsequent postexposure use of cytokines with organ-specific
      reparative functions.

PMID- 12793767
TI  - Ascorbate, added after irradiation, reduces the mutant yield and alters the
      spectrum of CD59- mutations in A(L) cells irradiated with high LET carbon ions.
AB  - It has been reported that X-ray induced HPRT- mutation in cultured human cells is
      prevented by ascorbate added after irradiation. Mutation extinction is attributed
      to neutralization by ascorbate, of radiation-induced long-lived radicals (LLR)
      with half-lives of several hours. We here show that post-irradiation treatment
      with ascorbate (5 mM added 30 min after radiation) reduces, but does not
      eliminate, the induction of CD59- mutants in human-hamster hybrid A(L) cells
      exposed to high-LET carbon ions (LET of 100 KeV/microm). RibCys, [2(R,S)-D-ribo
      1',2',3',4'-Tetrahydroxybutyl]-thiazolidene-4(R)-ca riboxylic acid] (4 mM) gave a
      similar but lesser effect. The lethality of the carbon ions was not altered by
      these chemicals. Preliminary data are presented that ascorbate also alters the
      spectrum of CD59- mutations induced by the carbon beam, mainly by reducing the
      incidence of small mutations and mutants displaying transmissible genomic
      instability (TGI), while large mutations are unaffected. Our results suggest that
      LLR are important in initiating TGI.

PMID- 12793768
TI  - Establishment and characterization of GSA-1, a human cell line highly susceptible
      to apoptosis after free-fall.
AB  - The induction of apoptosis by microgravity and/or gravity-changing stress is
      considered to be one of the important causes of cell death, although the
      molecular mechanisms of the apoptotic event remain unclarified. In this study, we
      established a cell line, GSA-1, from ethyl methanesulfonate-treated human RSa
      cells. GSA-1 cells were highly susceptible to apoptosis after a free-fall; 24.4%
      of these cells underwent apoptosis after free-fall, compared with only 6% of the
      RSa cells. The apoptosis of GSA-1 cells was augmented by ultraviolet (UV,
      principally 254-nm wavelength) irradiation before free-fall to a greater extents
      than those in RSa cells. The molecular mechanisms of apoptosis included p53 and
      Bax proteins; the expression of nuclear p53 and cytoplasmic Bax in GSA-1 cells
      increased at 4 h after free-fall irrespective of irradiation. In addition, the
      rate of removal of cyclobutane pyrimidine dimer (CPD) in UV-irradiated GSA-1
      cells was higher in cells exposed to free-fall than in those under the 1-G
      condition. Our results suggested that in GSA-1 cells, free-fall accelerates
      apoptosis, and that this process is associated with the accumulation of p53 and
      Bax, as well as CPD removal. Thus, GSA-1 cells should be useful for investigating
      the mechanism of cellular response, including the induction of apoptosis under
      gravity-changing stress.

PMID- 12793769
TI  - Protection of negative gravitaxis in Euglena gracilis Z against gamma-ray
      irradiation by Trolox C.
AB  - The protective effects of Trolox on the inhibition of negative gravitaxis in
      Euglena gracilis exposed to 200 Gy 60Co gamma-rays were examined using different
      concentrations (1, 10 and 100 microM). The orientation precision of the negative
      gravitaxis was quantified using the r-value. A significant decrease in the r
      value was observed in gamma-irradiated samples (0.18+/-0.03) compared to those of
      non-irradiated samples (0.47+/-0.03). There were no significant changes in the r
      value of cells exposed to 200 Gy gamma-rays by the addition of 1 or 10 microM of
      Trolox. A significant increase (0.19) in the r-value of cells exposed to 200 Gy
      with 100 microM Trolox was observed. The results indicates that Trolox at a
      concentration of 100 microM protects negative gravitaxis against 60Co gamma-ray
      irradiation at a dose of 200 Gy. It also suggests that the negative gravitaxis of
      Euglena gracilis is affected by free radicals.

PMID- 12793770
TI  - Hypergravity modifies the signal transduction of ionizing radiation through p53.
AB  - To determine the possible effect of hypergravity to modify the signal
      transduction of ionizing radiation, we analyzed the accumulation of p53 and the
      expression of p53-dependent genes, Waf-1 and Bax, using the western blot
      analysis. Hypergravity (20 x g) induced the accumulation of p53 in the human
      glioblastoma cell line A172 after 3 h of incubation. Low-dose (0.5 Gy)
      irradiation to the cells accumulated p53 1.5 h after irradiation, and induced Waf
      1 and Bax. Under the condition of hypergravity (20 x g), the peak of p53
      accumulation was shifted from 1.5 h to 3 h after irradiation, and the inductions
      of Waf-1 and Bax were suppressed entirely. These results indicate that
      hypergravity modifies the signal transduction of ionizing radiation through p53
      in the cells.

PMID- 12793771
TI  - In memory of Gautam D. Badhwar.

PMID- 12793772
TI  - The transmissible spongiform encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSEs) represent a group of
      neurodegenerative diseases characterised by a very long incubation period in
      regard to the life expectancy of the host species. The lesions are restricted to
      the central nervous system, although the pathogenesis of infection implies a
      primary replication step of TSE agents in the lymphoid organs followed by a
      neuroinvasive phase. The outcome is always fatal and today there is neither cure
      nor prophylaxis for these diseases. For years, the causative agents of TSEs have
      posed a conundrum in terms of current knowledge of microorganisms, and there are
      still open questions about their exact nature. They are usually called TSE agents
      or prions because they are thoughtto be primarily composed of a modified host
      protein, the prion protein (PrP). A pathological form of the prion protein,
      called PrPSc (for scrapie) or PrPRes, an operational definition referring to
      resistance to proteolytic digestion, accumulates in target organs. The aim of
      this introductory chapter is to presentthe general features of TSEs and a modern
      understanding of TSE agents and their mode of replication. Notwithstanding the
      plethora of unsolved questions on these diseases and their aetiology, knowledge
      of their pathogenesis and recent advances in understanding of the molecular basis
      of PrP accumulation, together with detection systems, provide the tools to
      conduct sound TSE risk management.

PMID- 12793773
TI  - Bovine spongiform encephalopathy.
AB  - Early epidemiological studies identified bovine spongiform encephalopathy as a
      feed-borne infection associated with infected meat-and-bone meal in animal feed.
      The infection may have derived from scrapie in sheep, a spontaneous genetic
      mutation in cattle, or a transmissible spongiform encephalopathy in another
      mammalian species. Experimental work on the risk of transmission has necessarily
      tried to identify risk materials and their infectivity levels, the nature and
      size of species barriers, the infectious dose, the route of infection, the strain
      of the agent and the genotype of the animals at risk. The identification of
      levels of infection in cattle tissues has aided the removal of risk materials
      from the human and animal food chains. Maternally associated transmission is
      unlikely to maintain an outbreak, but the offspring of clinical cases appear to
      be at greater risk when the rate of food-borne exposure is high. Studies of
      embryo transfer have not shown infection to be transmitted by this means. While
      the control measures appeared to be straightforward, compliance has at times
      proved difficult to enforce and quantify. This has necessitated more extensive
      prohibitions, aggressive enforcement and thorough auditing of compliance levels.

PMID- 12793774
TI  - Differential diagnosis of neurologically expressed disorders in Western European
      cattle.
AB  - A classification of neurological or neurologically expressed disorders that occur
      in Western European cattle aged 12 month and over has been established on the
      basis of aetiology, frequency and conditions of appearance, age and type of
      animals concerned and the main clinical signs observed. Neurologically expressed
      disorders have been classified according to different groups of causes:
      biological, non-biological and non-specific or unknown. Differential diagnosis of
      neurologically expressed disorders is an essential element in the clinical
      epidemiological surveillance of bovine spongiform encephalopathy. A growing
      number of aetiologies are described in the scientific literature. The
      identification and centralised management of neurological disorders will make it
      possible, one the one hand, to take account of the inherent variability in the
      clinical forms encountered and in the diagnostic approaches of the observers and,
      on the other hand, to identify new risk factors in order to control them.

PMID- 12793775
TI  - Bovine spongiform encephalopathy in sheep?
AB  - Bovine spongiform encephalopathy (BSE) in sheep has not been identified under
      natural conditions at the time of writing and remains a hypothetical issue.
      However, rumours about the possible finding of a BSE-like isolate in sheep have
      led to great unrest within the sheep industry, among the general public and
      within governmental and regulatory bodies. The difficulties of implementing a
      proper risk assessment and pre-emptive measures, in the absence of a confirmed
      case, are described. The authors attempt to list what is known about experimental
      BSE in sheep, the distribution of infectivity in the host, some aspects of risk
      assessment and management and the most promising methods for differentiating BSE
      from scrapie in the same host. As for the latter, new and promising methods are
      being developed and appear suitable for initial screening of isolates of
      transmissible spongiform encephalopathies, but in the absence of proper
      validation, use of the 'classical' strain-typing in a mouse panel is still
      indicated.

PMID- 12793776
TI  - The epidemiology of scrapie.
AB  - This review provides an update on the epidemiology of scrapie. The authors
      provide historical and recent information regarding the determination of
      geographical distribution, pathogenesis, transmission, genetic influence and the
      dynamics of scrapie within a flock. Also described are the risk factors
      associated with the disease and its spread within and between flocks. The current
      science may assist in providing a foundation on which prevention and control
      programmes may be based. Some examples of current national scrapie programmes are
      summarised.

PMID- 12793777
TI  - Transmissible spongiform encephalopathies in non-domestic animals: origin,
      transmission and risk factors.
AB  - The transmissible spongiform encephalopathies (TSEs), scrapie and bovine
      spongiform encephalopathy (BSE), are serious diseases of domestic animals.
      Although not as significant in terms of numbers of animals affected or
      geographical distribution, TSEs also affect non-domestic animals. Transmissible
      mink encephalopathy (TME) was the first TSE to be identified in non-domestic
      animals. This disease of captive mink (Mustela vison) is very rare and is
      associated with exposure through feed contaminated by a TSE agent. The second TSE
      to be identified in non-domestic animals was chronic wasting disease (CWD) of
      deer and elk. This disease is not known to be associated with feedstuffs
      contaminated with the agent of CWD, but the natural route of exposure appears to
      be oral, possibly through direct interaction between animals or through
      environmental contamination. Over the last five years, the known distribution of
      CWD across North America has expanded, increasing concerns over the impact of
      this disease on populations of free-ranging cervids and the viability of game
      farming industries. Concurrent with the epidemic of BSE, a variety of non
      domestic ruminants and felid species were also affected in the United Kingdom,
      presumably through exposure to the agent in contaminated feed. These examples
      illustrate that when non-domestic animals are held in captivity, they depend upon
      feeds supplied by their caretakers and may show degrees of susceptibility to
      infectious agents in feeds which vary from those of domestic species. Although
      humans have less influence over exposure of free-ranging species to infectious
      agents, monitoring these populations for diseases may be important for managing
      the health of these animals. It is important to institute or continue
      surveillance for an entire range of infectious diseases, including TSEs, in free
      ranging and captive non-domestic species. Study of diseases in these species may
      provide important information about infectious agents of concern for domestic
      animals and humans.

PMID- 12793778
TI  - Assessment of the risk factors related to bovine spongiform encephalopathy.
AB  - The Office International des Epizooties (OIE: World organisation for animal
      health) recommends that all OIE Member Countries determine the status of bovine
      spongiform encephalopathy (BSE) in their cattle populations by conducting a risk
      assessment and meeting certain BSE surveillance criteria. The OIE has identified
      and listed the factors and criteria for this in the International Animal Health
      Code. The factors to be assessed include the consumption of meat-and-bone meal
      (MBM) by cattle, the importation of cattle and MBM which are potentially infected
      or contaminated with the BSE agent, the livestock population structure, the
      rendering processes and the animal feeding practices. In this paper, the authors
      present an overview of these risk factors and criteria, detailing the relevant
      components of each. In the second part of this paper, the authors provide a risk
      assessment to demonstrate the application of the OIE BSE guidelines. This is a
      probabilistic risk assessment of the factors related to BSE for Canada which
      conforms to the OIE approach to import risk analysis. The steps include the
      hazard identification, release, exposure and consequence assessments and the risk
      estimation. A scenario tree for the release and exposure assessments was used to
      model the events emanating from the initiating failure event of importing cattle
      potentially infected with BSE. The consequence assessment describes the costs and
      losses associated with the introduction and establishment of BSE in other
      countries. The risk estimate, integrating the release, exposure and consequence
      assessments, indicates a negligible probability that BSE was introduced and
      established in Canada; nevertheless, the economic consequences would have been
      extreme.

PMID- 12793779
TI  - Risk management of transmissible spongiform encephalopathies in Europe.
AB  - Bovine spongiform encephalopathy (BSE) was first described in the United Kingdom
      (UK) in November 1986. After the introduction of an active surveillance system,
      most countries in Europe have reported BSE cases in the cattle population. This
      indicates that the use of active surveillance in addition to passive surveillance
      is important to assess the true BSE status in a country. Scrapie, a transmissible
      spongiform encephalopathy (TSE) in sheep and goats, has been reported in
      countries throughout the world with a few notable exceptions. Concern was
      expressed that BSE could have been introduced into sheep and goats. Currently,
      distinguishing between scrapie and BSE in small ruminants is only possible
      through lengthy experiments in mice. Preliminary results of active surveillance,
      introduced in 2002, show that significant under-reporting occurred. The history
      of BSE in cattle shows that risk assessments concerning the risk in a given
      country were often ignored and subsequent risk management decisions were
      inaccurate, i.e. although the risk was probable, no measures were taken in terms
      of either animal or human health. Furthermore, the effect of the measures taken
      was often overestimated and these had to be amended several times. The most
      important action to prevent new cases of TSEs occurring is by banning the feeding
      meat-and-bone meal (MBM) to ruminants. Further measures to be considered are the
      exclusion of specified risk material and carcasses from rendering, the process
      parameters for rendering of animal waste and the prevention of cross
      contamination of feed with MBM. The most important measures to protect the
      consumer are the ban on specified risk material, such as brain and spinal cord,
      which may contain particularly high concentrations of the BSE agent, and the ban
      on mechanically recovered meat. The most important measures taken in Europe and
      the scientific background thereof are described and discussed.

PMID- 12793780
TI  - Risk management of the transmissible spongiform encephalopathies in North
      America.
AB  - As North American Free Trade Agreement partners, Canada, the United States of
      America (USA) and Mexico apply independent but harmonised transmissible
      spongiform encephalopathy (TSE) risk management strategies in observance of
      Office International des Epizooties guidelines. The divergence between bovine
      spongiform encephalopathy (BSE) risk management approaches in North American and
      Europe reflects comparatively reduced external and internal BSE risks in North
      America. The external quarantine and internal surveillance measures adopted for
      BSE respond to several iterations of national risk assessments initiated in the
      early 1990s and revised as recently as 2002. Feed bans applied since 1997 to
      preclude establishment of BSE also bear the potential to limit intra-species and
      inter-species exposure to scrapie, chronic wasting disease (CWD) and
      transmissible mink encephalopathy (TME). Surveillance continues for the four TSEs
      through collaborative efforts of national and sub-national veterinary
      infrastructures and accompanying laboratory networks. Mexico has never identified
      the presence of any TSE. The last diagnosed case of TME in North America dates
      back to 1985. Since the only recognised appearance in Canada through an import
      from Great Britain in 1993, BSE has not been detected in North America. Scrapie
      and CWD remain at generally low prevalence in Canada and the USA. Independent but
      harmonised eradication programmes target elimination of the latter two diseases.

PMID- 12793781
TI  - Bovine spongiform encephalopathy in South America: a regional preventive
      approach.
AB  - Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle
      caused by prions that was first described in the United Kingdom (UK) in 1986. The
      BSE epizootic that commenced in the UK in the 1980s has since spread into other
      countries in Europe and Asia through exports of contaminated meat-and-bone meal
      or infected cattle. Over the past few years, other emerging or reemerging
      diseases have spread into previously free countries or regions through
      international trade. This negative effect of globalisation means that to
      implement successful preventive and strategic programmes to safeguard animal
      health, such programmes must, as a priority, take a regional approach. Global
      thinking, regional planning and local performance constitute the key factors for
      the successful control of animal diseases. In South America, initial preventive
      actions against BSE were adopted in 1989. Further measures adopted since then and
      based on new scientific and technical findings, have led to the demonstration
      that the region is free of BSE. These early preventive actions have reliably
      protected the region from importing BSE-infected material. An integral part of
      the project to determine the BSE status of South America was the training of
      personnel, the incorporation of technology and the provision of updated
      information through close relationships with international organisations and
      prominent international researcher workers. Regional activities aimed at
      harmonising BSE prevention programmes, producing objective and transparent data
      on the equivalence of regional BSE status and facilitating regional and
      international trade have recently been launched. Maintaining the BSE-free status
      of the region must be given high priority by the beef agro-industrial sectors.

PMID- 12793782
TI  - Risk management of transmissible spongiform encephalopathies in Asia.
AB  - A questionnaire-based survey was distributed to the Office International des
      Epizooties (OIE: World organisation for animal health) Member Countries in Asia
      to assess the use of risk management for transmissible spongiform
      encephalopathies. The author presents a summary of 16 responses received in July
      2002. The survey revealed that import risk analysis on bovine spongiform
      encephalopathy (BSE) is not routinely carried out in ten countries, indicating an
      urgent need for further training courses. Although the number of ruminants
      imported from Europe is relatively small, significant quantities of feedstuffs of
      ruminant origin have been imported into Asia, which may mean that the BSE agent
      could have reached domestic cattle in most countries. The external challenge has
      been considerably reduced in recent years as most countries in Asia banned the
      importation of feedstuffs from countries with BSE, but a few weak spots which
      enable imports of risk materials still persist. Recycling of BSE through
      rendering plants is unlikely but cannot be totally excluded in some countries
      such as the People's Republic of China, India, Japan, Pakistan and Taipei China.
      Therefore, much more stringent management at slaughterhouses and rendering
      plants, as well as extensive surveillance programmes, are required in those
      countries. Bovine spongiform encephalopathy is not notifiable in six countries,
      indicating a total absence of risk management of BSE in those countries.
      Immediate actions by these governments to declare BSE a notifiable disease are
      considered necessary. Numbers of specimens tested for BSE are still very small in
      most countries in Asia, indicating a pressing need to upgrade surveillance
      programmes by introducing modern (economically affordable) diagnostic methods and
      by conducting practical training courses on epidemiological surveillance systems.
      With the exception of Japan, very little work has been performed on scrapie in
      Asia although the disease has been routinely monitored in the People's Republic
      of China, India, Myanmar, Pakistan and Taipei China.

PMID- 12793783
TI  - Risk communication of the transmissible spongiform encephalopathies.
AB  - Previous chapters of this review have dealt with the scientific basis of
      assessing the risks from transmissible spongiform encephalopathies and how those
      risks should be managed. The author explores the theory and practice of risk
      communication and sets out the basic principles for good risk communication when
      dealing with uncertainty.

PMID- 12793784
TI  - Protein nutrition for ruminants in European countries, in the light of animal
      feeding regulations linked to bovine spongiform encephalopathy.
AB  - The outbreak of bovine spongiform encephalopathy (BSE) and the discovery of the
      central role played by meat-and-bone meal (MBM) as the vehicle of infection
      resulted, from the late 1980s onwards, in the implementation of new regulations
      on the incorporation of animal proteins, and then of most fats of animal origin,
      into diets fed to ruminants and other farmed animals. The BSE-related feed ban,
      which has gradually been reinforced over time, has led to the investigation of
      cost-effective routes for adequately replacing MBM and tallow by new sources of
      dietary proteins, minerals and lipids in the formulation of manufactured
      concentrates. As far as the technical fulfilment of the nutritive requirements of
      growing and lactating ruminants is concerned, efficient alternative solutions,
      based principally on recourse to food materials from vegetals already exist or
      hopefully will soon be available in most of the situations prevailing in Europe.
      However, related aspects, such as animal feed-processing, availability and
      traceability of certain food materials, quality of animal products, environmental
      constraints or disposal of animal waste from the meat industry give cause for
      concern. The expected consequences of the BSE-related feeding regulations on the
      organisational and economic framework of animal and crop production sectors
      throughout Europe and at world level must also be evaluated.

PMID- 12793785
TI  - An exploration of risk factors for bovine spongiform encephalopathy in ruminant
      production systems in the tropics.
AB  - The epidemic of bovine spongiform encephalopathy (BSE) in Europe in the late
      Twentieth Century required the interplay of two sets of factors, which now
      provide reference points for assessment of the BSE risk throughout the world. One
      set of factors consisted of the presence of infective agent in cattle or some
      other ruminant. The second set consisted of transmission and amplification of the
      disease, made possible through a particular feeding system that allowed
      persistent and habitual feeding of meat-and-bone meal (MBM) derived from cattle.
      The authors explore the ruminant production systems of three representative
      countries in South-East Asia against the background of factors required for the
      manifestation of BSE. The results can be extended to other countries in sub
      tropical and tropical regions where similar, non-industrial ruminant production
      systems operate. In short, the lack of a nutritionally or economically rational
      niche for MBM as a source of dietary protein or nitrogen in many ruminant
      production systems removes the hazard of BSE.

PMID- 12793786
TI  - The potential for transmissible spongiform encephalopathies in non-ruminant
      livestock and fish.
AB  - Pigs and poultry in the United Kingdom have undeniably been exposed to the bovine
      spongiform encephalopathy (BSE) agent. They consumed the same ruminant protein
      that gave rise to the BSE epidemic in cattle, but there has been no evidence of
      an epidemic in these species. Experimental investigations have shown pigs to be
      susceptible to infection by multiple parenteral challenge, but resistant to oral
      exposure with BSE-infected cattle brain. Current but incomplete evidence suggests
      that they are also resistant to oral challenge with sheep scrapie. Studies in
      domestic chickens indicate that they are resistant to both parenteral and oral
      challenge. Unfortunately, no published data exists on the susceptibility of fish
      to infection. Incidental findings in the brains of unexposed pigs are described
      that could otherwise give rise to concerns aboutthe presence of a transmissible
      spongiform encephalopathy in pig populations around the world.

PMID- 12793787
TI  - Rendering practices and inactivation of transmissible spongiform encephalopathy
      agents.
AB  - The authors describe the historic form of rendering and provide details on
      present-day practice. Possible future directions for the rendering industry are
      considered. The role of rendered meat-and-bone meal (MBM) as a dietary supplement
      in propagating the United Kingdom (UK) epidemic of bovine spongiform
      encephalopathy (BSE) is discussed, together with the role of MBM in spreading BSE
      outside the UK. Evidence that customarily used rendering processes did not
      substantially inactivate the agents of BSE or scrapie is presented. In addition,
      the influence that the abandonment of solvent extraction (as an adjunct to
      rendering) in the UK might have had on BSE infectivity levels in MBM is
      discussed. The BSE-related safety of tallow and by-products of tallow are
      considered. Data that associate the BSE agent with a new variant form of
      Creutzfeldt-Jakob disease in humans, predominantly but not exclusively, in the
      UK, are also discussed.

PMID- 12793788
TI  - An overview of tests for animal tissues in feeds applied in response to public
      health concerns regarding bovine spongiform encephalopathy.
AB  - Enforcing the ban on meat-and-bone meal in feed for farmed animals, and
      especially ruminants, is considered an important measure to prevent the spread of
      bovine spongiform encephalopathy. The authors describe current analytical methods
      for the detection and identification of animal tissues in feed. In addition,
      recently approved requirements, such as the ban of intra-species recycling
      (practice of feeding an animal species with proteins derived from the bodies, or
      parts of bodies, of the same species) are described. In principle, four different
      approaches are currently applied, i.e. microscopic analysis, polymerase chain
      reaction, immunoassay analysis and near infrared spectroscopy or microscopy. The
      principal performance characteristics of these methods are presented and
      compared, and their specific advantages and disadvantages described. Special
      emphasis is also placed on the impact of rendering conditions, particularly high
      temperatures and on the use of molecular biology techniques.

PMID- 12793789
TI  - Comparative analysis of lipid profiles among patients with type 2 diabetes
      mellitus, hypertension and concurrent type 2 diabetes, and hypertension: a view
      of metabolic syndrome.
AB  - Type 2 diabetes mellitus and hypertension are independent risk factors for
      atherosclerotic lesions that are partly linked with dyslipidaemia. This risk is
      additive when diabetes and hypertension occur concurrently. In order to determine
      if concurrent type 2 diabetes and hypertension results in putative increases in
      dyslipidaemia in a Nigerian population, we compared the plasma lipid levels,
      atherogenic index and prevalence of dyslipidaemia among age and sex-matched
      indigenous Nigerians with type 2 diabetes, hypertension and concurrent diabetes
      and hypertension. Age and sex-matched healthy Nigerians that are free of diabetes
      and hypertension served as controls. The patients as a whole were more likely to
      have dyslipidaemia than controls (p < 0.05). High-density lipoprotein cholesterol
      was similar among patients and controls. Mean total cholesterol, high-density
      lipoprotein cholesterol; low-density lipoprotein cholesterol and triglyceride
      levels, atherogenic index and prevalence of dyslipidaemia did not differ
      significantly among patients with hypertension, diabetes, and concurrent
      hypertension and diabetes (p = 0.99 for each parameter). It is concluded that
      concurrent hypertension and type 2 diabetes does not result in a more severe
      dyslipidaemia than when either of the two conditions occurs in isolation. We
      attribute this to the common pathogenic link between hypertension, diabetes and
      dyslipidaemia in metabolic syndrome. Evidence, albeit indirect, of this syndrome
      among native Africans is, therefore, provided.

PMID- 12793790
TI  - Predictors of outcome in hospitalized patients with severe hyponatremia.
AB  - Severe hyponatremia is associated with increased morbidity and mortality.
      Clinicians treating patients with severe hyponatremia are often torn between a
      desire to promptly raise serum sodium concentration to a "safe range," and at the
      same time, to avoid excessively rapid correction of hyponatremia. The aim of this
      study was to assess the prevalence of severe hyponatremia in hospitalized
      patients, the etiologic factors involved, as well as treatment and outcome of the
      patients using a retrospective case series. METHODS: Retrospective study of 168
      patients with severe hyponatremia (< 115mmol/L) seen at Grady Memorial Hospital,
      a tertiary teaching hospital, in Atlanta, Georgia, from 1997-2001. The main
      outcome measures of interest were death during admission or occurrence of
      neurologic symptoms before, during or after therapy. RESULTS: One hundred sixty
      eight patients met the inclusion criteria out of a total of 5994 patients with
      hyponatremia treated at our hospital over the study period. Eighty-nine patients
      (52.9%) were symptomatic. The mean absolute serum sodium at 48-hours of therapy
      was 120.02 +/- 8.31 mmol/L. Respiratory failure and/or hypoxia was present in 28
      patients (16.7%); sepsis was documented in 16 patients (9.5%). Mortality rate was
      high, 34 patients died (20.2%). On multivariate analysis factors with strong
      association with mortality of patients with severe hyponatremia were hypoxia,
      presence of neurologic symptoms, slow correction rates and a diagnosis of sepsis.
      CONCLUSIONS: The mortality associated with severe hyponatremia remains high.
      Sepsis, respiratory failure and the presence of symptoms predict poor outcome in
      hospitalized patients with severe hyponatremia. More aggressive therapy with 3%
      saline may improve outcome in symptomatic patients. Our data suggest that a slow
      rate of correction in severe hyponatremia is associated with higher mortality
      than rapid correction, at least in the short-term.

PMID- 12793791
TI  - Significant asymptomatic bacteriuria among Nigerian type 2 diabetics.
AB  - Significant asymptomatic bacteriuria is a risk factor for symptomatic urinary
      infection and septicemia among predisposed individuals such as diabetics. We
      investigated the pattern of asymptomatic bacteriuria among our type 2 diabetics
      with a view to documenting the prevalence, type of organisms responsible and the
      antibiotic susceptibility pattern. One hundred and twenty-four type 2 Nigerian
      diabetics (55 males and 69 females) submitted midstream urine specimens for
      culture. Thirty-three patients had significant bacteriuria (9 males and 24
      females), showing the frequency of occurrence of asymptomatic bacteriuria to be
      26.6%. The most common organism isolated was Klebsiella pneumonia at 42.4%. Gram
      negative bacilli made up about 23 (69.7%) of the isolates. Isolates were poorly
      sensitive to the readily available antibiotics (ampicillin, tetracycline and
      cotrimoxazole), but a large number of the organisms isolated were sensitive to
      nitrofurantoin, gentamicin, ciprofloxacin and ofloxacin. Sensitivity to
      erythromycin, nalidixic acid and cefuroxime was moderate. Asymptomatic
      bacteriuria is, thus, more prevalent among the Nigerian diabetic population than
      in the non-diabetics. A changing pattern of disease is observed with Klebsiella
      sp. now accounting for the majority of asymptomatic bacteriuria among diabetics.
      The organisms are not sensitive to the commonly available antibacterial agents.

PMID- 12793792
TI  - Antimicrobial susceptibility patterns of urinary pathogens in Trinidad, 1996
      1999.
AB  - The prevalence of antimicrobial resistance among urinary pathogens has been
      increasing worldwide. Laboratory diagnosed urinary tract infections were
      retrospectively evaluated for the years 1996 through 1999, to document the common
      pathogens and their changing antimicrobial profiles. From 14,853 hospital
      specimens, an isolation rate of 6.1% was found; and from 5330 community
      specimens, the isolation rate was 27.9%. E. coli was the predominant cause of
      urinary tract infections in both hospital and community practices. The rate of
      isolation of the other pathogens was relatively stable except for citrobacter
      species, which increased from 1.3% in 1996 to 20.1% in 1999 (p < 0.001) among
      community isolates. Significant changes in the susceptibility patterns of
      uropathogens also were observed. E. coli strains from hospitals were
      significantly more resistant to cefuroxime than community strains (p < 0.001),
      while resistance to ampicillin and nalidixic acid was high in both practices. No
      substantial changes in susceptibility to gentamicin and tetracycline were noticed
      during the four-year period compared to the 99% resistance to tetracycline in
      1995. In relation to nitrofurantoin, no significant changes were noted in both
      practices where resistant rates remained low, but susceptibility to augmentin
      showed much improvement among all isolates, including E. coli. Urinary isolates
      were more commonly recovered from the paediatric age group (1-10 years) and those
      older than 50 years of age, and males were the predominant gender in both age
      groups. The study showed that the antibiotics useful in the treatment of UTI in
      decreasing order of effectiveness in community practice were gentamicin,
      norfloxacin, nitrofurantoin and cefuroxime. For nosocomial UTI, the drugs most
      effective include norfloxacin, nitrofurantoin, gentamicin, co-trimoxazole and
      amoxicillin-clavulanic acid.

PMID- 12793794
TI  - Self-image, self-concept, and self-identity revisited.
AB  - Observation, research, experimentation, and verification are the foundational
      processes giving rise to principles. Principles imply fundamental truths upon
      which rest knowledge, learning, and teaching. Knowledge and principles are
      memorialized by and disseminated through words. The denotative word meanings must
      be agreed upon in order that principles and knowledge can be formally written and
      spoken. In this way, the structure of scientific information can be built. Three
      significant psychological terms failing to meet these criteria are self-image,
      self-concept, and self-identity. Their significance comes from being foundational
      stones in the structure of one's self-esteem. To illustrate some of the confusion
      related to them, randomly selected definitions from the psychological literature
      are presented for the sake of comparison. The purpose of this paper is to attempt
      to reach a better understanding of these three terms. What will not be discussed
      here are any literature theories, like Erikson's eight identity stages or
      Cooley's social interaction "Looking-glass self."

PMID- 12793795
TI  - The foundation of self-esteem.
AB  - Self-esteem is a simplistic term for varied and complex mental states pertaining
      to how one views oneself. It takes but little research in the voluminous
      literature to see the vagueness and inconsistencies in its various definitions.
      Even more problematic is the uncertainty concerning its foundational components.
      The importance of having a solid definition and specific ideas about the
      foundational components of self-esteem is that both pave the way to recognizing
      its causes; to predicting effects from those causes; and to organizing the
      trouble-shooting process for locating those philosophical flaws or psychological
      scars which lead to low self-esteem. The purpose of this paper is to offer a
      common ground for thinking about self-esteem at its most basic level. In order to
      distinguish the "basic level" from the rest of the components of self-esteem, let
      us liken it to a skyscraper building. Here, the focus is on the building's
      "underground foundation" and the base upon which that foundation rests. The base
      is a definition that allows for the assessment of the foundation. The underground
      foundation itself consists of the mental building blocks called self-meaning,
      self-identity, self-image, and self-concepts. To help illustrate their
      interactions, a few of the "masks" and "faces" of self-esteem will be mentioned.
      What is not being addressed is the "above ground structure"--those theories and
      manifestations dealt with by most mental health specialists.

PMID- 12793793
TI  - Syphilis and human immunodeficiency virus co-infection.
AB  - Co-infection of syphilis and AIDS has profound implications for the African
      American community. The purpose of this review is to: evaluate the historical
      background of HIV and syphilis and their similarities in pathogenesis; review the
      epidemiology of syphilis and HIV co-infection, and implications for continued
      prevention efforts; examine the effect of syphilis on HIV transmission and
      acquisition; and, to examine the effects of HIV infection on syphilis
      transmission, diagnostic and serologic changes, clinical course, and treatment.
      The prevalence of HIV is higher in those with syphilis; moreover, the prevalence
      of HIV and syphilis co-infection is highest in African Americans. There may be
      humoral and cellular immune similarities. HIV may affect the transmission of
      syphilis, alter its serologic diagnosis, and accelerate and change the clinical
      course and response to treatment. In conclusion, combined infection of HIV and
      syphilis may alter the clinical presentation and course of either disease. There
      are historical and immunologic similarities and the high prevalence in African
      Americans compared to other groups is of great importance for prevention efforts.

PMID- 12793796
TI  - Visual function in patients with optic nerve pallor (optic atrophy).
AB  - This cross-sectional study assessed the relationship between the degree of optic
      nerve pallor (optic atrophy) and visual function. Using a set of "gold standard"
      stereoscopic slides, the severity of optic atrophy for 270 eyes, each having
      sustained a bout of optic neuropathy, was graded. Good visual acuity was found in
      55/86 (64.0%) mild, 54/119 (45.4%) moderate, and 21/65 (32.3%) marked optic
      atrophy eyes. Good visual field was found in 6/28 (21.4%) mild, 4/43 (9.3%)
      moderate, and 2/28 (7.1%) marked optic atrophy eyes. Good color vision was found
      in 31/46 (67.4%) mild, 12/62 (19.4%) moderate, and 7/31 (22.6%) marked optic
      atrophy eyes. A significant rank correlation was observed between optic atrophy
      and visual acuity (P < 0.001; rs = 0.356), visual field (P < 0.001; rs = -0.398),
      and color vision (P < 0.001; rs = -0.492). As the graded severity of optic
      atrophy increases, the proportion of eyes with good visual function decreases.
      Visual field, rather than visual acuity or color vision, appears to be a better
      indicator of the severity of visual loss, when optic atrophy is present.

PMID- 12793797
TI  - The laxative.

PMID- 12793798
TI  - African AIDS and American medicine.

PMID- 12793799
TI  - Ethnic differences in incidence of diseases and response to medicines.

PMID- 12793800
TI  - Lack of access to good healthcare & obese African-American women.

PMID- 12793801
TI  - Attitudes toward the attire of African-American medical students, residents, and
      early career physicians.

PMID- 12793802
TI  - Crystal structure and magnetic properties of an ionic C60 complex with
      decamethylcobaltocene: (Cp*2Co)2C60(C6H4Cl2, C6H5CN)2. Singlet-triplet
      transitions in the C60(2-) anion.
AB  - The C(60) complex with decamethylcobaltocene, (Cp(2)Co)(2)C(60)(C(6)H(4)Cl(2),
      C(6)H(5)CN)(2) (1) (C(6)H(4)Cl(2) = 1,2-dichlorobenzene; C(6)H(5)CN =
      benzonitrile), has been obtained as single crystals by the diffusion method. The
      IR and UV-vis-NIR spectra show the presence of the C(60)(2)(-) and the Cp(2)Co(+)
      ions, which form a three-dimensional framework with channels accommodating
      solvent molecules. EPR and SQUID measurements show that C(60)(2)(-) has a
      diamagnetic singlet (S = 0) state in the 2-140 K range. The appearance of a broad
      EPR signal and the increase in magnetic susceptibility of 1 above 140 K are
      assigned to a thermal population of a close lying triplet (S = 1) state. The
      singlet-triplet energy gap for C(60)(2)(-) in solid 1 is estimated to be 730+/-10
      cm(-)(1).

PMID- 12793803
TI  - A novel organic-inorganic hybrid based on a dinuclear copper complex supported on
      a keggin polyoxometalate.
AB  - The autoassembly process of copper-oxalate dimers and Keggin type
      polyoxometalates leads to the first example of a new family of organic-inorganic
      hybrids, K(14)[(Cu(2)(bpy)(2)(mu
      ox))(SiW(11)O(39)Cu(H(2)O))](2)[SiW(11)O(39)Cu(H(2)O)]. approximately 55H(2)O.
      This compound crystallizes in the monoclinic space group C2/m, a = 37.932(6) A, b
      = 21.303(3) A, c = 12.546(2) A, beta = 106.16(1) degrees, Z = 2. The crystal
      structure reveals the presence of a polymeric hybrid built up of alternating
      dimer and polyoxometalate entities.

PMID- 12793804
TI  - Aromatic hydrocarbon-catalyzed direct reaction of sulfur and sodium in a
      heterogeneous system: selective and facile synthesis of sodium monosulfide and
      disulfide.
AB  - Sodium disulfide and monosulfide were selectively formed via the direct reaction
      of sulfur and an equimolar amount of sodium in 1,2-dimethoxyethane at 70 degrees
      C in the presence of a catalytic amount of aromatic hydrocarbons and ketone.

PMID- 12793805
TI  - Speciation and unusual reactivity in PuO2+x.
AB  - Pu L(3) XAFS measurements show that the excess oxygen in single phase
      PuO(2+)(x)() occurs as oxo groups with Pu-O distances of 1.83-1.91 A. This
      distance and the energy of the edge (via comparison with a large number of
      related compounds) are more consistent with a Pu(IV/V) than a Pu(IV/VI) mixture.
      Analogous to Pu(IV) colloids, although the Pu-Pu pair distribution remains single
      site even when it shows substantial disorder, the Pu-O distribution can display a
      number of additional shells at specific distances up to 3.4 A even in high fired
      materials when no oxo groups are present, implying intrinsic H(+)/OH(-)(/H(2)O).
      The number of oxo atoms increases when samples are equilibrated with humid air at
      ambient temperature, indicating that the Pu reactivity in this solid system
      differs notably from that of isolated complexes and demonstrating the importance
      of nanoscale cooperative phenomena and total free energy in determining its
      chemical properties.

PMID- 12793806
TI  - Self-exchange reaction kinetics of metallocenes revisited: insights from the
      decamethylferricenium-decamethylferrocene reaction at variable pressure.
AB  - Rate constants k(ex) and volumes of activation deltaV(ex) have been obtained
      using (1)H NMR for the self-exchange reaction of the [(eta(5)
      C(5)(CH(3))(5))(2)Fe](+) hexafluorophosphate and tetrafluoroborate with [(eta(5)
      C(5)(CH(3))(5))(2)Fe] in acetone-d(6) (deltaV(ex) = -8.6 +/- 0.3 cm(3) mol(
      )(1)), dichloromethane-d(2), and (semiquantitatively) in acetonitrile-d(3). Under
      the experimental conditions, ion pairing was significant only in CD(2)Cl(2), but
      even that produced only a minor reduction in k(ex) and so had a negligible effect
      on deltaV(ex) ( = -6.4 +/- 0.2 cm(3) mol(-)(1) with PF(6)(-)). In all cases,
      deltaV(ex) is negative and consistent with a simple two-sphere activation model,
      rather than with that of Weaver et al. (Nielson, R. M.; McManis, G. E.; Safford,
      L. K.; Weaver, M. J. J. Phys. Chem. 1989, 93, 2152) in which the barrier crossing
      rate is limited by solvent dynamics. Similarly, the approximately 5-fold increase
      in k(ex) on going from [(eta(5)-C(5)H(5))(2)Fe](+/0) to [(eta(5)
      C(5)(CH(3))(5))(2)Fe](+/0) in acetone can be explained with the two-sphere model
      on the basis of the effects of reactant size on the solvent reorganization
      energy, without reference to solvent dynamics.

PMID- 12793807
TI  - APdCu(Se2)(Se3) (A = K and Rb): new quaternary copper palladium polyselenides
      with unusual metal-selenium coordination.
AB  - Two novel metal polyselenides, KPdCu(Se(2))(Se(3)) (I) and RbPdCu(Se(2))(Se(3))
      (II), have been synthesized from solvothermal reactions in superheated
      ethylenediamine at 160 degrees C. The isostructural compounds crystallize in the
      monoclinic space group P2(1)/m, Z = 2, with a = 6.145(1) A, b = 7.268(1) A, c =
      8.865(2) A, beta = 102.41(3) degrees for I, and a = 6.253(1) A, b = 7.267(1) A, c
      = 8.993(2) A, beta = 102.28(3) degrees for II. Their crystal structures are two
      dimensional networks with [PdCu(Se(2))(Se(3))](-) anionic layers built from one
      dimensional [Pd(Se(2))(Se(3))](2)(-) "chains" that are "stitched" together by
      tetrahedrally coordinated Cu atoms. The DSC data show that I and II are stable up
      to 400 degrees C and decompose at ca. 436 and 424 degrees C, respectively. Both
      compounds are narrow band-gap semiconductors with estimated band gaps of about
      0.7 eV (I) and 0.8 eV (II), respectively. They are the first structurally
      characterized quaternary copper palladium polychalcogenides with a (Se(2))(2)(-)
      and a (Se(3))(2)(-) fragment, both exhibiting interesting and unusual metal
      selenium coordination.

PMID- 12793808
TI  - Vanadogermanate cluster anions.
AB  - Three novel vanadogermanate cluster anions have been synthesized by hydrothermal
      reactions. The cluster anions are derived from the (V(18)O(42)) Keggin cluster
      shell by substitution of V=O(2+) "caps" by Ge(2)O(OH)(2)(4+) species. In
      Cs(8)[Ge(4)V(16)O(42)(OH)(4)].4.7H(2)O, 1, (monoclinic, space group C2/c (No.
      15), Z = 8, a = 44.513(2) A, b = 12.7632(7) A, c = 22.923(1) A, beta = 101.376(1)
      degrees ) and (pipH(2))(4)(pipH)(4)[Ge(8)V(14)O(50).(H(2)O)] (pip =
      C(4)N(2)H(10)), 2 (tetragonal, space group P4(2)/nnm (No. 134), Z = 2, a =
      14.9950(7) A, c = 18.408(1) A), two and four VO(2+) caps are replaced,
      respectively, and each cluster anion encapsulates a water molecule. In
      K(5)H(8)Ge(8)V(12)SO(52).10H(2)O, 3, (tetragonal, space group I4/m (No. 87), Z =
      2, a = 15.573(1) A, c = 10.963(1) A), four VO(2+) caps are replaced by
      Ge(2)O(OH)(2)(4+) species, and an additional two are omitted. The cluster ion in
      3 contains a sulfate anion disordered over two positions. The cluster anions are
      analogous to the vanadoarsenate anions [V(18)(-)(n)()As(2)(n)()O(42)(X)](m)(-) (X
      = SO(3), SO(4), Cl; n = 3, 4) previously reported.

PMID- 12793809
TI  - Formation of a novel 1D supramolecule [HgCl2(ptz)]2.HgCl2 (ptz = phenothiazine):
      a new precursor to submicrometer Hg2Cl2 rods.
AB  - A novel supramolecule [HgCl(2)(ptz)](2).HgCl(2) (ptz = phenothiazine) with
      uncoordinated inorganic salt HgCl(2) presented in a 1D chain was first prepared
      and then successfully applied as a new precursor in the preparation of
      submicrometer Hg(2)Cl(2) rods. Single crystal X-ray analysis showed that the 1D
      chain structure is stabilized by hydrogen bonds between adjacent chains and the
      coordination mode of the ligand phenothiazine is unusual with large steric
      inhibition other than the chain directions. The results revealed that the
      particular chain structure plays a significant role in the formation of the
      Hg(2)Cl(2) rods.

PMID- 12793810
TI  - Multidimensional frameworks assembled from silver(I) coordination polymers
      containing flexible bis(thioquinolyl) ligands: role of the intra- and
      intermolecular aromatic stacking interactions.
AB  - The two flexible multidentate ligands 1,3-bis(8-thioquinolyl)propane (C3TQ) and
      1,4-bis(8-thioquinolyl)butane (C4TQ) were reacted with AgX (X = CF(3)SO(3)(-) or
      ClO(4)(-)) to give four new complexes: ([Ag(C3TQ)](ClO(4)))(n)() 1,
      ([Ag(C3TQ)](CF(3)SO(3)))(n)() 2,
      ([Ag(2)(C4TQ)(CF(3)SO(3))(CH(3)CN)](CF(3)SO(3)))(n)() 3, and
      ([Ag(C4TQ)](ClO(4)))(n)() 4. All complexes have been characterized by elemental
      analysis, IR, and (1)H NMR spectroscopy. Single-crystal X-ray analysis showed
      that chain structures form for all complexes in which the quinoline rings
      interact via various intra- (1) or intermolecular (2, 3, and 4) pi-pi aromatic
      stacking interactions, which in the latter cases results in multidimensional
      structures. Additional weak interactions, such as Ag.O and Ag.S contacts and C
      H.O hydrogen bonding, are also present and help form stable, crystalline
      materials. It was found that the (CH(2))(n) spacers (n = 3 or 4) affect the
      orientation of the two terminal quinolyl rings, thereby significantly influencing
      the specific framework structure that forms. If the same ligand is used, on the
      other hand, then the different counteranions have the greatest effect on the
      final structure.

PMID- 12793811
TI  - Influences of changes in multitopic tris(pyrazolyl)methane ligand topology on
      silver(I) supramolecular structures.
AB  - The reactions between silver tetrafluoroborate and the ligands 1,2,4,5
      C(6)H(2)[CH(2)OCH(2)C(pz)(3)](4) (L1, pz = pyrazolyl ring), o
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2) (L2), and m-C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)
      (L3) yield coordination polymers of the formula (C(6)H(6)(
      )(n)[CH(2)OCH(2)C(pz)(3)](n)(AgBF4)(m))( infinity ) (n = 4, m = 2, 1; n = 2,
      ortho substitution, m = 1, 2; meta substitution, m = 2, 3). In the solid state,
      L2 molecules dimerize by a pair of C-H.pi interactions, forming an arrangement
      that resembles the tetratopic ligand L1. In the solid-state structure of 1, each
      silver atom is kappa(2)-bonded to two tris(pyrazolyl)methane units from different
      ligands with the overall structure a polymer made up from 32-atom macrocyclic
      rings formed by bonding tris(pyrazolyl)methane groups from nonadjacent positions
      on the central arene rings to the same two silver atoms. In 2, each silver is
      bonded to two tris(pyrazolyl)methane units in the same kappa(2)-kappa(2) fashion
      as with 1, forming a polymer chain. The chains are organized into dimeric units
      by strong face-to-face pi-pi stacking between the central arene rings making
      bitopic L2 act as half of tetratopic L1. The chains in both structures are
      organized by weak C-H.F hydrogen bonds and pi-pi stacking interactions into very
      similar 3D supramolecular architectures. The structure of 3 contains three types
      of silvers with the overall 3D supramolecular sinusoidal structure comprised of
      32-atom macrocycles. Infrared studies confirm the importance of the noncovalent
      interactions. Calculations at the DFT (B3LYP/6-31G) level of theory have been
      carried out on L2 and also support C-H.pi interactions. Electrospray mass
      spectral data collected from acetone or acetonitrile show the presence of
      aggregated species such as [(L)Ag(2)(BF(4))](+) and [(L)Ag(2)](2+), despite the
      fact that (1)H NMR spectra of all compounds show that acetonitrile completely
      displaces the ligand whereas acetone does not.

PMID- 12793812
TI  - X-ray and neutron diffraction studies on "Li4.4Sn".
AB  - A chemical analysis and detailed structural characterization, using X-ray single
      crystal and neutron powder diffraction, of the binary lithium-tin compound
      "Li(4.4)Sn" is presented. Phase analyses and subsequent structural refinements
      result in the reformulation of "Li(4.4)Sn" as Li(17)Sn(4). The lithium-rich
      binary phase crystallizes with a complex cubic structure in the space group
      Ffourmacr;3m, with a = 19.6907(11) A, Z = 20. The improved crystal structure
      determination indicates well-defined lithium atom positions, some of which differ
      from those previously reported. The nearly Zintl phase Li(17)Sn(4) exhibits poor
      metallic behavior similar to that of heavily doped semiconductors. Comparisons of
      the refined crystal structure with previously reported X-ray crystal structures
      associated with "Li(4.4)Sn" are discussed.

PMID- 12793813
TI  - Synthesis and characterization of platinum diimine bis(acetylide) complexes
      containing easily derivatizable aryl acetylide ligands.
AB  - New Pt(II) diimine bis(acetylide) complexes where the diimine is a substituted
      bipyridine or phenanthroline and the arylacetylide is 4-ethynylbenzaldehyde have
      been prepared in good to excellent yields. Spectroscopic characterization
      supports a square planar coordination geometry with cis-alkynyl ligands, and the
      crystal structure of one of the complexes, Pt(phen)(Ctbd1;CC(6)H(4)CHO)(2) (1),
      confirms the assignment. The new diimine bis(acetylide) complexes exhibit an
      absorption band ca. 400 nm that corresponds to a Pt(d) --> pi diimine charge
      transfer transition and are brightly emissive in fluid solution, with excited
      state lifetimes in the range 100-800 ns. Correlation of diimine substituent with
      lambda(max) for the 400 nm absorption band gives strong support to the MLCT
      assignment. Complex 1 undergoes electron transfer quenching, showing good Stern
      Volmer behavior with a variety of oxidative and reductive quenchers. Quenching
      studies conducted with DNA nucleosides (A, T, C, G) were also investigated. Silyl
      protected adenosine and guanosine were found to quench the luminescence of 1
      better than similarly protected cytidine or thymidine. Since the former are the
      more easily oxidized bases, the results suggest that the Pt(II) diimine
      bis(acetylide) complexes are more powerful photooxidants than photoreductants
      with regard to electron transfer to DNA bases.

PMID- 12793814
TI  - Induced fit process in the selective distal binding of imidazoles in zinc(II)
      porphyrin receptors.
AB  - The respective affinities of various imidazole derivatives, imidazole (ImH), 2
      methylimidazole (2-MeImH), 2-phenylimidazole (2-PhImH), N-methylimidazole (N
      MeIm), 2-methylbenzimidazole (2-MeBzImH), and 4,5-dimethylbenzimidazole (4,5
      Me(2)BzImH), for two phenanthroline (Phen) strapped zinc(II) porphyrin receptors
      porphen-Zn 1-Zn and 2-Zn have been studied. The formation of a supplementary H
      bond considerably enhances the affinity of the zinc(II)-porphen receptor for
      imidazoles unsubstituted on the pyrrolic nitrogen (ImH) versus N-substituted
      imidazoles such as N-MeIm. The ImHs subset porphen-Zn complexes are formed with
      association constants up to 4 orders of magnitude superior to those measured
      either for N-MeIm as substrate or TPP-Zn as receptor. Distal or proximal binding
      of the substrates was determined by (1)H NMR measurements and titration. In two
      cases, the very high stability of the inclusion complex enabled the use of 2D NMR
      techniques. Excellent correlation between solution and solid-state structures has
      been obtained. A total of six X-ray structures are detailed in this article
      showing that the evolution of the shape of the zinc(II) receptor is mostly
      dependent on the steric constraints induced by the substitution on the imidazole.
      Hindered guests also progressively induce considerable mobility restrictions and
      severe distortions on the receptor, especially in the case of 2-MeBzImH and 2
      PhImH.

PMID- 12793815
TI  - Cation-cation interactions in neptunyl(V) compounds: hydrothermal preparation and
      structural characterization of NpO2(IO3) and alpha- and beta-AgNpO2(SeO3).
AB  - The hydrothermal reaction of NpO(2) with IO(3)(-) in the presence of nitrate
      results in the formation of NpO(2)(IO(3)) (1). Under similar conditions, NpO(2)
      reacts with AgNO(3) and SeO(2) to yield alpha-AgNpO(2)(SeO(3)) (2) and beta
      AgNpO(2)(SeO(3)) (3). The structure of 1 consists of distorted pentagonal
      bipyramidal Np(V) centers that are bridged by iodate anions. In addition, the oxo
      atoms of the neptunyl(V) cations coordinate adjacent Np(V) centers creating
      layers that are linked into a three-dimensional network structure by the iodate
      anions. The structure is polar owing to the alignment of the stereochemically
      active lone pair of electrons on the iodate anions along the c-axis. alpha
      AgNpO(2)(SeO(3)) (2) forms a layered structure consisting of hexagonal
      bipyramidal NpO(8) polyhedra that are bound by chelating and bridging selenite
      anions. The primary and secondary structures of 3 are similar to those of 1, and
      neptunyl-neptunyl interactions are partially responsible for the creation of a
      three-dimensional network structure. However, the selenite anions in 3 are
      rotated with respect to the iodate anions found in 1, and the structure is
      centrosymmetric. The network found in 3 consists of interconnecting,
      approximately square channels that house the Ag(+) cations. A bond-valance sum
      parameter of 2.036 A for Np(V) bound exclusively to oxygen has been developed
      with b = 0.37 A. Crystallographic data: 1, orthorhombic, space group Pna2(1), a =
      13.816(2) A, b = 5.8949(8) A, c = 5.5852(8) A, Z = 4; 2, monoclinic, space group
      P2(1)/n, a = 4.3007(3) A, b = 9.5003(7) A, c = 11.5877(9) A, beta = 95.855(1)
      degrees, Z = 4; 3, triclinic, space group Ponemacr;, a = 7.1066(6) A, b =
      8.3503(7) A, c = 8.3554(7) A, alpha = 89.349(1) degrees, beta = 77.034(1)
      degrees, gamma = 76.561(1) degrees, Z = 2.

PMID- 12793816
TI  - Direct determination of the Gibbs' energy of formation of peroxynitrous acid.
AB  - The kinetics of decomposition of peroxynitrous acid (ONOOH) was investigated in
      the presence of 0.1-0.75 M HClO(4) and at a constant ionic strength. The decay
      rate of ONOOH decreased in the presence of H(2)O(2), approaching a limiting value
      well below 75 mM H(2)O(2). It also decreased in the presence of relatively low
      [HNO(2)] but did not approach a lower limiting value, since ONOOH reacts directly
      with HNO(2). The latter reaction corresponds to a HNO(2)- and H(+)-catalyzed
      isomerization of ONOOH to nitrate, and its third-order rate constant was
      determined to be 520 +/- 30 M(-)(2) s(-)(1). The mechanism of formation of
      O(2)NOOH from ONOOH in the presence of H(2)O(2) was also scrutinized. The results
      demonstrated that in the presence of 0.1-0.75 M HClO(4) and 75 mM H(2)O(2) the
      formation of O(2)NOOH is insignificant. The most important finding in this work
      is the reversibility of the reaction ONOOH + H(2)O right harpoon over left
      harpoon HNO(2) + H(2)O(2), and its equilibrium constant was determined to be (7.5
      +/- 0.4) x 10(-)(4) M. Using this value, the Gibbs' energy of formation of ONOOH
      was calculated to be 7.1 +/- 0.2 kcal/mol. This figure is in good agreement with
      the value determined previously from kinetic data using parameters for radicals
      formed during homolysis of peroxynitrite.

PMID- 12793817
TI  - Cationic carbonyl complexes of rhodium(I) and rhodium(III): syntheses,
      vibrational spectra, NMR studies, and molecular structures of
      tetrakis(carbonyl)rhodium(I) heptachlorodialuminate and -gallate,
      [Rh(CO)4][Al2Cl7] and [Rh(CO)4][Ga2Cl7].
AB  - Dimeric rhodium(I) bis(carbonyl) chloride, [Rh(CO)(2)(mu-Cl)](2), is found to be
      a useful and convenient starting material for the syntheses of new cationic
      carbonyl complexes of both rhodium(I) and rhodium(III). Its reaction with the
      Lewis acids AlCl(3) or GaCl(3) produces in a CO atmosphere at room temperature
      the salts [Rh(CO)(4)][M(2)Cl(7)] (M = Al, Ga), which are characterized by Raman
      spectroscopy and single-crystal X-ray diffraction. Crystal data for
      [Rh(CO)(4)][Al(2)Cl(7)]: triclinic, space group Ponemacr; (No. 2); a = 9.705(3),
      b = 9.800(2), c = 10.268(2) A; alpha = 76.52(2), beta = 76.05(2), gamma =
      66.15(2) degrees; V = 856.7(5) A(3); Z = 2; T = 293 K; R(1) [I > 2sigma(I)] =
      0.0524, wR(2) = 0.1586. Crystal data for [Rh(CO)(4)][Ga(2)Cl(7)]: triclinic,
      space group Ponemacr; (No. 2); a = 9.649(1), b = 9.624(1), c = 10.133(1) A; alpha
      = 77.38(1), beta = 76.13(1), gamma = 65.61(1) degrees; V = 824.4(2) A(3); Z = 2;
      T = 143 K; R(1) [I > 2sigma(I)] = 0.0358, wR(2) = 0.0792. Structural parameters
      for the square planar cation [Rh(CO)(4)](+) are compared to those of
      isoelectronic [Pd(CO)(4)](2+) and of [Pt(CO)(4)](2+). Dissolution of
      [Rh(CO)(2)Cl](2) in HSO(3)F in a CO atmosphere allows formation of
      [Rh(CO)(4)](+)((solv)). Oxidation of [Rh(CO)(2)Cl](2) by S(2)O(6)F(2) in HSO(3)F
      results in the formation of ClOSO(2)F and two seemingly oligomeric Rh(III)
      carbonyl fluorosulfato intermediates, which are easily reduced by CO addition to
      [Rh(CO)(4)](+)((solv)). Controlled oxidation of this solution with S(2)O(6)F(2)
      produces fac-Rh(CO)(3)(SO(3)F)(3) in about 95% yield. This Rh(III) complex can be
      reduced by CO at 25 degrees C in anhydrous HF to give [Rh(CO)(4)](+)((solv));
      addition of SbF(5) at -40 degrees C to the resulting solution allows isolation of
      [Rh(CO)(4)][Sb(2)F(11)], which is found to have a highly symmetrical (D(4)(h)())
      [Sb(2)F(11)](-) anion. Oxidation of [Rh(CO)(2)Cl](2) in anhydrous HF by F(2),
      followed in a second step by carbonylation in the presence of SbF(5), is found to
      be a simple, straightforward route to pure [Rh(CO)(5)Cl][Sb(2)F(11)](2), which
      has previously been structurally characterized by us. All new complexes are
      characterized by vibrational and NMR spectroscopy. Assignment of the vibrational
      spectra and interpretation of the structural data are supported by DFT
      calculations.

PMID- 12793818
TI  - Synthesis and characterization of trans-[Os(en)2py(H)]2+ and related studies.
AB  - trans-[Os(en)(2)pyH](Otf)(2), 2, is recovered from an acidic solution of trans
      [Os(en)(2)py(H(2))](OTf)(2), 1, which has been subjected to one electron
      oxidation. The structures of both 1 and 2 have been determined by single crystal
      X-ray analysis. In cyclic voltammetry, 2 shows a one electron oxidation wave at
      0.95 V and a one electron reduction wave at -1.2 V, neither accompanied by a
      signal for the reverse process. Reduction of 2 by Zn/Hg in methanol solution
      leads to quantitative formation of [Os(en)(2)(py)H(2))](2+), predominantly in the
      trans-form. In aqueous solution, species 2 reacts rapidly with N-methylacridium
      ion, [MAH](+), by hydride transfer. One electron chemical oxidation of 2 to the
      corresponding Os(IV) is slower than that of 1 to 2 owing to the increase in
      coordination number when Os(IV) is produced. Treatment of 1, or the cis-form, 1',
      in DMSO by sodium t-butoxide produces mainly the corresponding isomers of the
      monohydrides of Os(II), that derived from 1' is deep red in color while the trans
      monohydride is colorless. Both react with [MAH](+) to form [MAH](2), and both
      disappear rapidly in acetone or acetonitrile, presumably by reducing the
      solvents. Reaction of trans-[Os(NH(3))(4)(H(2))H(2)O](BPh(4))(2), 4, in acetone
      d(6) as solvent with either CH(3)CHO or styrene leads to hydrogenation of the
      substrate. Reactions which compete with trans-[Os(en)(2)(eta(2)
      H(2))(CF(3)SO)(3)]CF(3)SO(3) release of substrate from the trans-complex before
      isomerization to the cis-form, required for hydrogenation to occur, result in the
      trans-derivative of the added solute. When H(2)C=CH-CH(2)-SCH(3) is the
      substrate, binding takes place at sulfur. Complete conversion to the cis
      substrate isomer is observed, without hydrogenation occurring even though contact
      between dihydrogen and the double bond is possible.

PMID- 12793819
TI  - A unique mechanism for base catalyzed hydrolysis of pentaaminecobalt(III)
      complexes containing picolyl residues.
AB  - A novel [Co(pentaamine)Cl](2+) complex having all tertiary amine or pyridine
      donors has been synthesized (pentaamine = 1,4-bis(2'-pyridyl)-7-methyl-1,4,7
      triazacyclononane). This asym-[Co(dmpmetacn)Cl](2+) species has been completely
      characterized through 1D and 2D NMR studies, and through the X-ray structure for
      the ZnCl(4)(2)(-) salt. Despite the lack of an activating NH center, remarkably
      its hydrolysis to [Co(pentaamine)OH](2+) is base catalyzed (k(OH) 0.70 M(-)(1) s(
      )(1), 25 degrees C, I = 1.0 M, NaCl). Detailed NMR studies reveal that the base
      catalyzed substitution leads to the exchange of just one deuterium in one of the
      two -CH(2)- pyridyl arms, that is approximately trans to the leaving group, and
      this occurs during and not after base hydrolysis. Quenching experiments for the
      reaction of asym-[Co(dmpmetacn)Cl](2+) and control experiments on H/D exchange
      for the product asym-[Co(dmpmetacn)OD](2+) in OD(-) show that each act of
      deprotonation at the acidic methylene leads to loss of Cl(-). This is the first
      established case of base catalyzed substitution for a complex where the effective
      site of deprotonation is at a pyridyl group. A pronounced kinetic isotope effect
      is observed for the species perdeuterated at the pyridyl methylenes (k(H)/k(D) =
      5.0), consistent with rate limiting deprotonation which is a rare event in
      Co(III) substitution chemistry. The activation afforded by the carbanion is
      discussed in terms of a new process coined the pseudo-aminate mechanism.

PMID- 12793820
TI  - Self-assembly of dialkyltin(IV) moieties and aromatic dicarboxylates to complexes
      with a polymeric or a discrete trinuclear macrocyclic structure in the solid
      state and a mixture of fast interchanging cyclooligomeric structures in solution.
AB  - It is well-known that the structures of trialkyltin(IV) carboxylates can be
      either monomeric, polymeric, or cyclooligomeric in the solid state. In contrast,
      all dialkyltin(IV) dicarboxylates characterized so far in the solid state have
      monomeric or polymeric structures, however, for some cases it has been proposed
      that their solution-state structure is cyclooligomeric. In order to generate more
      information on this subject, dimethyl- and di-n-butyltin(IV) complexes with
      phthalic and isophthalic acid have been prepared and analyzed both in solution
      and in the solid state. The solid-state structures of the two dialkyltin(IV)
      phthalates examined herein contain polymeric molecular chains, however, with
      supramolecular Sn.O' interactions, which result in the generation of
      cyclooligomeric units. This provides evidence for the presence of discrete
      cyclooligomeric structures in solution, which are involved in fast dynamic
      exchange equilibria as evidenced by (1)H, (13)C, and (119)Sn NMR spectroscopy. In
      the case of the two dialkyltin(IV) isophthalate complexes studied herein (R = Me,
      n-Bu), only the di-n-butyltin derivative is soluble and NMR spectroscopy as well
      as FAB(+) spectrometry indicates the formation of cyclic dinuclear, trinuclear,
      and/or tetranuclear species in solution, which may be involved also in fast
      dynamic exchange equilibria. In the solid state, however, discrete
      cyclotrinuclear units can be identified, in which the 24-membered macrocyclic
      cavity is almost completely planar, having six oxygen atoms directed into its
      interior and six Sn-n-butyl groups approximately perpendicular to the molecular
      plane. The diameter of the cyclic cavity can be described by the transannular O.O
      distances that vary from 7.68 to 7.84 A, being large enough for the introduction
      of linear alkyl groups. This can be demonstrated by the supramolecular structure
      of this compound, which contains a new type of bis[2]pseudorotaxane formed
      between two molecules through mutual threading via two of the Sn-butyl groups.
      Such a supramolecular entity has been unknown so far, since the usual composition
      of bis[2]pseudorotaxanes is the trimolecular combination of a macrocyclic ring
      system with two threads.

PMID- 12793821
TI  - The platinum catalyst [bpyrPtCl2] in superacidic solution.
AB  - The methane oxidation catalyst [bpyrPtCl(2)] (bpyr = bis-pyrimidine) dissolves in
      superacidic HF/SbF(5) solution under formation of a dinuclear cation
      [H(2)bpyrPt(mu-Cl)(2)PtbpyrH(2)](6+). Two crystal forms are isolated,
      [Pt(2)Cl(2)bpyr(2)H(4)](6+)(SbF(6)(-))(4)(Sb(2)F(11)(-))(2).2HF (I) (triclinic,
      Ponemacr;, a = 814.8(2) pm, b = 1444.8(3) pm, c = 2300.5(5) pm, alpha = 89.627(4)
      degrees, beta = 84.285(4) degrees, gamma = 84.665(4) degrees, Z = 2) and
      [Pt(2)Cl(2)bpyrH(4)](6+)(Sb(2)F(11)(-))(6).4HF (II) (triclinic, Ponemacr;, a =
      879.4(2) pm, b = 1170.4(3) pm, c = 1789.9(5) pm, alpha = 95.37(2) degrees, beta =
      99.97(2) degrees, gamma = 100.41(2) degrees, Z = 1). The cation in I has an angle
      of 148.4(1) degrees between the two square plane platinum environments, while the
      cation in II is fully planar. The non-platinum-bound nitrogen atoms are all
      protonated in the superacidic medium.

PMID- 12793822
TI  - Structural diversity of lithium sulfenamides: 7Li NMR studies in solution and
      crystal structures of [Li2(eta2-(CH3)3C-NS-C6H4CH(3)-4)2(THF)2] and [Li2(eta1-4
      CH3C6H4-NS-C6H4CH(3)-4)2(THF)4].
AB  - Two lithium sulfenamides were prepared by reaction of (CH(3))(3)C-N(H)-S
      C(6)H(4)CH(3)-4 (1) and 4-CH(3)C(6)H(4)-N(H)-S-C(6)H(4)CH(3)-4 (2) with an
      alkyllithium. The unsolvated sulfenamide Li[(CH(3))(3)C-NS-C(6)H(4)CH(3)-4] (3)
      was soluble enough for variable-temperature (VT) (7)Li NMR to provide evidence of
      a dynamic exchange of oligomers in solution. The crystal structures of the
      solvated sulfenamides of [Li(2)(eta(2)-(CH(3))(3)C-NS-C(6)H(4)CH(3)
      4)(2)(THF)(2)] (4) and of [Li(2)(eta(1)-4-CH(3)C(6)H(4)-NS-C(6)H(4)CH(3)
      4)(2)(THF)(4)] (6) consisted of dimers in which the anions display different
      hapticities. The VT (7)Li NMR spectra of 4 suggest that the two different
      structures exist in equilibrium in toluene-THF mixtures. These compounds are
      easily oxidized to the neutral thioaminyl radicals as identified by EPR
      spectroscopy.

PMID- 12793823
TI  - Conformational preferences driven by the C-methyl substituent in chelated o
      diphenylphosphino-alpha-methyl-N,N-dimethylbenzylamine rhodium complexes.
AB  - The stereochemistry of the chelate rings of a number of rhodium aminophosphine
      complexes is studied by NMR spectroscopy. The similarity in the variable
      temperature behavior for the different compounds is consistent with them having
      in common highly preferred chelate ring conformations. The six-membered
      metallacycle of coordinated (R)-PN (PN = o-diphenylphosphino-alpha-methyl-N,N
      dimethylbenzylamine) adopts a delta conformation in the solid state. NMR
      experiments indicate that this conformation is strongly favored in solution as
      well. The preferred sense of helicity is imposed by the absolute configuration of
      the stereogenic carbon atom on the ligand, which exerts an important steric
      control. The complex
      [Rh(TFB)((C(6)H(4)CHMeNMe(2))(2)P(C(6)H(4)CHMeNHMe(2)))](BF(4))(2).H(2)O.Me(2)CO
      crystallizes in the monoclinic space group P2(1) with a = 12.0548(11) A, b =
      16.139(2) A, c = 12.1804(10) A, beta = 100.742(9) degrees, Z = 4.

PMID- 12793824
TI  - Ligand close packing and the geometry of the fluorides of the nonmetals of
      periods 3, 4, and 5.
AB  - This paper discusses the geometry of the fluorides of the nonmetals of periods 3,
      4, and 5 in terms of the ligand close packing (LCP) model according to which
      molecular geometry is determined primarily by ligand-ligand repulsions (Pauli
      closed shell repulsions) rather than by the bonding and lone pair Pauli
      repulsions of the VSEPR model. The LCP model becomes the dominant factor in
      determing geometry when the ligands are sufficiently crowded that they may be
      regarded as essentially incompressible. Ligand close packing is a modification of
      the VSEPR model in which ligand-ligand repulsion (Pauli closed shell repulsion)
      is given more emphasis than bonding and nonbonding electron pair Pauli repulsion.
      The nonmetals of period 3 are large enough to form octahedral six coordinated
      molecules in which the ligands are close packed. The larger nonmetals of period 4
      also have a maximum coordination number of six and an octahedral geometry
      although the ligands are not close packed. Ligand radii derived from the
      interligand distances in the molecules of period 3 depend only on the charge of
      the fluorine ligands and are consistent with the previously derived radii
      obtained from the fluorides of the close packed tetrahedral molecules of the
      period 2 elements. Although the ligands in the molecules of the period 4
      nonmetals are not close packed, these elements are not large enough to form
      molecules with a higher coordination number. However, the larger period 5
      nonmetals may have coordination numbers of seven and eight. The seven coordinated
      molecules have a pentagonal bipyramidal geometry in which the equatorial ligands
      are close packed. The eight coordinated molecules have a square antiprism
      geometry, which is not a close packed geometry although the fluorine interligand
      distances are only a little larger than expected for close packing. The
      difference between the axial and equatorial bond lengths in the trigonal
      bipyramidal pentafluorides and the pentagonal bipyramidal pentafluorides can be
      understood on the basis of ligand close packing. Ligand packing prevents the lone
      pair in AF(6)E molecules from fully entering the valence shell and thereby
      exerting its full stereochemical effect so that these molecules have a C(3)(v)()
      distorted octahedral geometry rather than a geometry based on pentagonal
      bipyramidal seven coordination.

PMID- 12793825
TI  - Do penta- and decaphospha analogues of lithocene anion and beryllocene exist?
      Analysis of stability, structure, and bonding by hybrid density functional study.
AB  - Stability in penta- and decaphospha analogues of lithocene anion and beryllocene
      is investigated by complete structural optimization at the B3LYP/6-31G level.
      Natural bond orbital analysis is carried out to examine the bonding between the
      metal and the ligands. The heterolytic dissociation energies of 667 and 608
      kcal/mol predicted by B3LYP/6-311+G//B3LYP/6-31G calculations for CpBeP(5) and
      (P(5))(2)Be are comparable with the observed value of 635 +/- 15 kcal/mol in
      ferrocene. The high stability in CpBeP(5) and (P(5))(2)Be shows that these
      species are isolable under appropriate conditions. Lithocene anion and its
      phospha analogues possess lower stability toward dissociation into ionic
      fragments. A novel observation of the present study is that CpBeP(5) and
      (P(5))(2)Be have lowest energies when the two planar ligands are arranged
      perpendicular to each other such that one of the ligands, cyclo-P(5), is eta(1)
      coordinated while the second ligand is eta(5)-coordinated to Be. The resulting
      structure having C(s)() point group (denoted as C(s)()(p)) is predicted to be 22
      and 28 kcal/mol lower than the staggered sandwich geometry in CpBeP(5) and
      (P(5))(2)Be, respectively, at the B3LYP/6-311+G//B3LYP/6-31G level. In the
      analogous lithocene anions [CpLiP(5)](-) and [(P(5))(2)Li](-) also the C(s)()(p)
      structures are found to be the lowest energy structures, though their relative
      stabilities are small. We also characterized the geometry with both ligands
      eta(1)-coordinated to the metal in a linear arrangement having the D(2)(h)()
      point group in the decaphospha analogues [(P(5))(2)Li](-) and (P(5))(2)Be. This
      structure is found to be higher in energy than the C(s)()(p) structure. The
      D(2)(h)() structure could not be located as a potential minimum in the
      biscyclopentadienyl complexes and their pentaphospha analogues. Both the
      C(s)()(p) and D(2)(h)() structures are characterized for the first time in
      metallocenes. The D(2)(h)() structure seems to be a unique feature in the
      decaphospha metallocenes under consideration. Covalent bond formation between
      beryllium and phosphorus atom P(1) of eta(1)-(cyclo-P(5)) is more pronounced
      (bond orders 0.43-0.49) than that between Be and C(1) of eta(1)-Cp (bond orders
      0.24-0.27). Though both eta(1)-coordinated cyclo-P(5) and Cp exhibit C(2)(v)()
      point groups, bond alternation is less pronounced in the former. The Wiberg P-P
      bond orders in the eta(1)-(cyclo-P(5)) of CpBeP(5) and (P(5))(2)Be having
      C(s)()(p) structures are in the range 1.29-1.47. These ring bond orders indicate
      that the P(5) ring retains aromaticity to a large extent in the eta(1)-mode of
      bonding with Be. Second-order perturbational energy analysis of the Fock matrix
      in the natural bond orbital basis reveals that there is a significant stabilizing
      interaction of approximately 123 kcal/mol between the lone pair orbital of P(1)
      and the 2s orbital of Be in the C(s)()(p) structures.

PMID- 12793826
TI  - 11B, 23Na, 27Al, and 19F NMR study of solid and molten Na3AlF6-Na2B4O7.
AB  - High temperature electrochemical synthesis is a very promising method for the
      production of refractory boride powders and coatings. The Na(2)B(4)O(7)
      Na(3)AlF(6) binary system is part of the more complex NaCl-Na(3)AlF(6)
      Na(2)B(4)O(7)-TiO(2) electrolyte proposed for TiB(2) electrosynthesis. A new
      approach by high temperature and high resolution solid state nuclear magnetic
      resonance was employed for the structural description of this system, from the
      solid at room temperature to the liquid at 1100 degrees C. The change in (27)Al,
      (23)Na, (11)B, and (19)F NMR spectra with composition give evidence for the
      insertion of aluminum into the glassy network of Na(2)B(4)O(7) as [AlO(4)] and
      diluted [AlF(6)] units as well as formation of [BOF(2)] groups into solidified
      mixtures. A devitrification mechanism of glassy Na(2)B(4)O(7) under influence of
      Na(3)AlF(6) addition and temperature was discussed in terms of lowering boron
      coordination and obtaining oxyfluoride species.

PMID- 12793827
TI  - Electron transfer through a prenucleated bimetalated alanine-based peptide helix.
AB  - We have synthesized a 22 residue alanine-based peptide with a
      tris(bipyridyl)ruthenium(II) amino acid near the middle of the peptide which can
      act as a photoinducible electron donor. Two histidines spaced i, i + 4 near the C
      terminus of the peptide were then cross-linked with a tetraammineruthenium(III)
      moiety to prenucleate the helix and provide an electron acceptor site.
      Introduction of the cross-link enhances the average helix content from 67% to 84%
      at 0 degrees C, as judged by circular dichroism spectroscopy. The temperature
      dependence of the mean molar residue ellipticity at 222 nm, [THETAV;](222), for
      the bimetalated peptide was fit to a modified Lifson-Roig helix-coil model to
      permit extraction of the population of helical conformation at each residue
      separating the electron donor and acceptor. On average, the residues between the
      donor and acceptor are 92% helical. Photoinduced electron transfer with a driving
      force of -1.0 eV and an estimated reorganization energy of 0.82 eV was measured
      by fluorescence quenching methods in H(2)O and D(2)O, yielding rate constants,
      k(ET), of 7 +/- 3 x 10(6) s(-)(1) and 5 +/- 1 x 10(6) s(-)(1) at 0 degrees C.
      Calculation of the electronic coupling matrix element, H(ab), with the Marcus
      equation yields a value of 0.19 +/- 0.4 cm(-)(1). Analysis in terms of the
      pathway model for electronic coupling indicates that this magnitude of H(ab) is
      consistent with the participation of hydrogen bonds in electronic coupling for an
      isolated alpha-helix.

PMID- 12793828
TI  - Interpretation of the magnetic structures of Cu2Te2O5X2 (X = Cl, Br) and
      Ca3.1Cu0.9RuO6 on the basis of electronic structure considerations: cases for
      strong super-superexchange interactions involving Cu2+ ions.
AB  - For super-superexchange interactions between Cu(2+) ions, a qualitative rule was
      formulated to assess their strengths based on the geometrical parameters of the
      exchange paths. Spin dimer analysis was carried out for Cu(2)Te(2)O(5)X(2) (X =
      Cl, Br) and Ca(3.1)Cu(0.9)RuO(6) to evaluate the relative strengths of their
      superexchange and super-superexchange interactions. The strongest
      antiferromagnetic interactions in Cu(2)Te(2)O(5)X(2) (X = Cl, Br) are given by
      the super-superexchange interactions involving the most linear Cu-X.X-Cu paths
      between tetrahedral clusters Cu(4)O(8)X(4) along the (a +/- b)-directions. The
      adjacent CuRuO(6) chains of Ca(3.1)Cu(0.9)RuO(6) are antiferromagnetically
      coupled through the most linear Cu-O.O-Cu paths along the direction perpendicular
      to the plane of the CuRu zigzag chain. The spin lattices of Cu(2)Te(2)O(5)X(2)
      and Ca(3.1)Cu(0.9)RuO(6) deduced from our spin dimer analysis are consistent with
      the available magnetic data. The spin lattice of a magnetic solid should be
      determined on the basis of appropriate electronic structure considerations.

PMID- 12793829
TI  - Pyrazolato-bridged polynuclear palladium and platinum complexes. Synthesis,
      structure, and reactivity.
AB  - Cyclic trinuclear complexes [Pd(3)(mu-pz)(6)] (1) and [Pd(3)(mu-4-Mepz)(6)] (2)
      and dinuclear complex [Pd(2)(mu-3-t-Bupz)(2)(3-t-Bupz)(2)(3-t-BupzH)(2)] (3) have
      been prepared by the reactions of [PdCl(2)(CH(3)CN)(2)] with pyrazole (pzH), 4
      methylpyrazole (4-MepzH), and 3-tert-butylpyrazole (3-t-BupzH), respectively, in
      CH(3)CN in the presence of Et(3)N. In the absence of the base, treatment of
      [PdCl(2)(CH(3)CN)(2)] with pzH gave the mononuclear complex, [Pd(pzH)(4)]Cl(2)
      (6). The reaction of [PtCl(2)(C(2)H(5)CN)(2)] with pzH in the presence of Et(3)N
      under refluxing in C(2)H(5)CN afforded the known dimeric Pt(II) complex,
      [Pt(pz)(2)(pzH)(2)](2) (7). The protons participating in the hydrogen bonding in
      3 and 7 are easily replaced by silver ions to give the heterotetranuclear complex
      [Pd(2)Ag(2)(mu-3-t-Bupz)(6)] (4) and the heterohexanuclear complex [Pt(2)Ag(4)(mu
      pz)(8)] (5). The complexes 1-6 are structurally characterized.

PMID- 12793830
TI  - [Au(CN)4]- as a supramolecular building block for heterobimetallic coordination
      polymers.
AB  - A series of the first coordination polymers using the [Au(CN)(4)](-) anion as a
      building block has been prepared. The planar tetracyanoaurate anion uses one,
      two, or four cyano groups to bridge to Ni(II) or Cu(II) centers and exhibits weak
      Au(III)-N(cyano) interactions between anions. Ni(en)(2)[Au(CN)(4)](2).H(2)O (1,
      en = ethylenediamine) is a molecular compound with the two [Au(CN)(4)](-) anions
      coordinating in a trans orientation to Ni(II) without further cyanide
      coordination. Cu(dien)[Au(CN)(4)](2) (2, dien = diethylenetriamine) forms a
      similar molecular complex; however, the dimensionality is increased through weak
      intermolecular Au-N(cyano) interactions of 3.002(14) A to form a 1-D zigzag
      chain. Cu(en)(2)[Au(CN)(4)](2) (3) also forms a molecular complex similar to 1,
      but with elongated axial bonds. The complex further aggregates through Au
      N(cyano) interactions of 3.035(8) A to form a 2-D array. In
      [Cu(dmeda)(2)Au(CN)(4)][Au(CN)(4)] (4, dmeda = N,N-dimethylethylenediamine) one
      [Au(CN)(4)](-) anion coordinates via two cis-N(cyano) donors to the axial sites
      of two Cu(II) centers to form a 1-D zigzag chain of alternating
      [Cu(dmeda)(2)](2+) and [Au(CN)(2)](-) units; the other [Au(CN)(4)](-) anion forms
      a 1-D chain via Au-N(cyano) interactions. In
      [Cu(bipy)(H(2)O)(2)(Au(CN)(4))(0.5)][Au(CN)(4)](1.5) (5, bipy = 2,2'-bipyridine)
      one [Au(CN)(4)](-) anion uses all four cyano moieties to bridge four different
      Cu(II) centers, creating a 1-D chain.

PMID- 12793831
TI  - Nickel complexes of o-amidochalcogenophenolate(2-)/o
      iminochalcogenobenzosemiquinonate(1-) pi-radical: synthesis, structures, electron
      spin resonance, and x-ray absorption spectroscopic evidence.
AB  - The preparation of complexes trans-[Ni(-SeC(6)H(4)-o-NH-)(2)](-) (1), cis-[Ni(
      TeC(6)H(4)-o-NH-)(2)](-) (2), trans-[Ni(-SC(6)H(4)-o-NH-)(2)](-) (3), and [Ni(
      SC(6)H(4)-o-S-)(2)](-) (4) by oxidative addition of 2-aminophenyl dichalcogenides
      to anionic [Ni(CO)(SePh)(3)](-) proves to be a successful approach in this
      direction. The cis arrangement of the two tellurium atoms in complex 2 is
      attributed to the intramolecular Te.Te contact interaction (Te.Te contact
      distance of 3.455 A). The UV-vis electronic spectra of complexes 1 and 2 exhibit
      an intense absorption at 936 and 942 nm, respectively, with extinction
      coefficient epsilon > 10000 L mol(-)(1) cm(-)(1). The observed small g
      anisotropy, the principal g values at g(1) = 2.036, g(2) = 2.062, and g(3) =
      2.120 for 1 and g(1) = 2.021, g(2) = 2.119, and g(3) = 2.250 for 2, respectively,
      indicates the ligand radical character accompanied by the contribution of the
      singly occupied d orbital of Ni(III). The X-ray absorption spectra of all four
      complexes show L(III) peaks at approximately 854.5 and approximately 853.5 eV.
      This may indicate a variation of contribution of the Ni(II)-Ni(III) valence
      state. According to the DFT calculation, the unpaired electron of complex 1 and 2
      is mainly distributed on the 3d(xz)() orbital of the nickel ion and on the
      4p(z)() orbital of selenium (tellurium, 5p(z)()) as well as the 2p(z)() orbital
      of nitrogen of the ligand. On the basis of X-ray structural data, UV-vis
      absorption, electron spin resonance, magnetic properties, DFT computation, and X
      ray absorption (K- and L-edge) spectroscopy, the monoanionic trans-[Ni(
      SeC(6)H(4)-o-NH-)(2)](-) and cis-[Ni(-TeC(6)H(4)-o-NH-)(2)](-) complexes are
      appositely described as a resonance hybrid form of Ni(III)-bis(o
      amidochalcogenophenolato(2-)) and Ni(II)-(o-amidochalcogenophenolato(2-))-(o
      iminochalcogenobenzosemiquinonato(1-) pi-radical; i.e., complexes 1 and 2 contain
      delocalized oxidation levels of the nickel ion and ligands.

PMID- 12793832
TI  - Copper-63 NMR line width study of the copper(I)-acetonitrile system.
AB  - The principal focus of this study is the (63)Cu NMR line widths in Cu(I)
      acetonitrile (AN) solutions. The variations with the concentrations of Cu(I)
      salts (trifluoromethanesulfonate and perchlorate), added salts, water, chloride
      ion, and temperature have been studied. A quantitative analysis shows that the
      anomalous temperature dependence of the line widths is not due to ion pairing or
      anion complexation but results primarily from formation of a species with a
      different coordination number or less symmetrical arrangement of AN ligands than
      in the normal tetrahedral Cu(AN)(4)(+) ion. Solvent viscosity and ion pairing
      (with triflate) also are identified as factors having the expected effects on the
      line widths. The results of earlier studies also are discussed and analyzed by
      the current model where possible.

PMID- 12793833
TI  - The ligand effect on the hydrolytic reactivity of Zn(II) complexes toward
      phosphate diesters.
AB  - The catalytic effects of the Zn(II) complexes of a series of poliaminic ligands
      in the hydrolysis of the activated phosphodiesters bis-p-nitrophenyl phosphate
      (BNP) and 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) have been investigated.
      The reactions show first-order rate dependency on both substrate and metal ion
      complex and a pH dependence which is diagnostic of the acid dissociation of the
      reactive species. The mechanism of the metal catalyzed transesterification of
      HPNP has been assessed by solvent isotopic kinetic effect studies and involves
      the intramolecular nucleophilic attack of the substrate alcoholic group,
      activated by metal ion coordination. The intrinsic reactivity of the different
      complexes is controlled by the nature and structure of the ligand: complexes of
      tridentate ligands, particularly if characterized by a facial coordination mode,
      are more reactive than those of tetradentate ligands which can hardly allow
      binding sites for the substrate. In the case of tridentate ligands that form
      complexes with a facial coordination mode, a linear Bronsted correlation between
      the reaction rate (log k) and the pK(a) of the active nucleophile is obtained.
      The beta(nuc) values are 0.75 for the HPNP transesterification and 0.20 for the
      BNP hydrolysis. These values are indicated as the result of the combination of
      two opposite Lewis acid effects of the Zn(II) ion: the activation of the
      substrate and the efficiency of the metal coordinated nucleophile. The latter
      factor apparently prevails in determining the intrinsic reactivity of the Zn(II)
      complexes.

PMID- 12793834
TI  - Structures and magnetic behavior of 1-, 2-, and 3D coordination polymers in the
      Cu(II)-dicyanamide-pyrimidine family.
AB  - Using aqueous conditions, three new coordination polymers containing Cu(2+)
      cations, dicyanamide (dca) anions, and pyrimidine (pym) were isolated and
      structurally and magnetically characterized. Comprising the bulk of the product
      yield, Cu(dca)(2)(pym)(2), 1, crystallizes in the monoclinic space group P2(1)/c
      with a = 7.3569(5) A, b = 13.4482(9) A, c = 7.4559(5) A, beta = 98.984(3)
      degrees, and V = 728.6(1) A and forms linear 1D chains. The second compound,
      Cu(dca)(NO(3))(pym)(H(2)O), 2, is also monoclinic, P2(1)/n, with a = 7.6475(3) A,
      b = 12.2422(5) A, c = 11.0286(4) A, beta = 106.585(2) degrees, and V = 989.6(1)
      A(3). A 2D network structure consisting of both bridging mu-dca and pym ligands
      is formed while the NO(3)(-) and H(2)O are axially bonded to the Cu center.
      Cu(3)(dca)(6)(pym)(2).0.75H(2)O, 3, is triclinic, Ponemacr;, with a = 7.7439(4)
      A, b = 9.3388(5) A, c = 10.1779(5) A, alpha = 86.014(2) degrees, beta = 88.505(2)
      degrees, gamma = 73.623(2) degrees, and V = 704.46(9) A(3). The structure of 3 is
      quite unique in that [Cu(3)(pym)(2)](6+) trimers are interconnected via mu-dca
      ligands affording a complex 3D self-penetrating framework. Magnetically, 1
      exhibits extremely weak exchange interactions along the Cu-(dca)(2)-Cu ribbons
      while 2 and 3 display very strong magnetic couplings mediated by the mu-bonded
      pym ligands. Moreover, 2 shows a broad maximum in chi(T) at 40 K and behaves as a
      uniform 1D antiferromagnetic chain with g = 2.09(1), J/k(B) = -42.6(1) K, and TIP
      = -66 x 10(-)(6) emu/mol. An S = (1)/(2) trimer model that includes intertrimer
      interactions successfully described the magnetic behavior of 3, yielding g =
      2.10(1), J/k(B) = -69.4(5) K, theta = -0.28(3) K, and TIP = -180 x 10(-)(6)
      emu/mol. It is found that mu-bonded dca and pym ligands mediate very weak and
      very strong exchange interactions, respectively, between Cu(2+) centers.

PMID- 12793835
TI  - Stereoselective oxidative additions of iodoalkanes and activated alkynes to a
      sulfido-bridged heterotrinuclear early-late (TiIr2) complex.
AB  - The reactions of the early-late trinuclear complex [Cp(acac)Ti(mu(3)
      S)(2)Ir(2)(CO)(4)] (1) with electrophiles have been found to occur on the iridium
      atoms with no other involvement of the early metal than in electronic effects.
      The reaction with iodine gave two isomers of the diiridium(II) complex
      [Cp(acac)Ti(mu(3)-S)(2)Ir(2)I(2)(CO)(4)] differentiated by the relative positions
      of the iodo ligands on the iridium atoms. The reactions with iodoalkanes are
      highly stereoselective to give one sole isomer of formula [Cp(acac)Ti(mu(3)
      S)(2)Ir(2)(R)(I)(CO)(4)] (R = CH(3), CH(2)I, CHI(2)) with a carbonyl and the iodo
      ligand trans to the metal-metal bond. The structures of the symmetrical isomer
      with the iodo ligands trans to the metal-metal bond and that of the compound with
      R = CHI(2) have been solved by X-ray diffraction methods. The stereoselectivity
      of the oxidative-addition reactions can be rationalized assuming the influence of
      steric effects of the groups on the titanium center and a radical-like mechanism.
      Reactions of 1 with the activated acetylenes, dimethylacetylenedicarboxylate and
      methylacetylenecarboxylate, gave the complexes [Cp(acac)Ti(mu(3)-S)(2)Ir(2)(mu
      eta(1)-RC=CCO(2)Me)(CO)(4)] (R = CO(2)Me, H), with the alkyne bridging the two
      iridium centers as a cis-dimetalated olefin and the C=C bond parallel to the Ir
      Ir axis. Two isomers resulting from the disposition of the alkyne along the Ir-Ir
      vector were observed in solution for the compound with the nonsymmetrical alkyne
      (R = H), while only one was observed for the compound with R = CO(2)Me. An
      exchange, fast in the NMR time scale, of the apical with the equatorial carbonyls
      occured in the complexes [Cp(acac)Ti(mu(3)-S)(2)Ir(2)(mu-eta(1)
      RC=CCO(2)Me)(CO)(4)], producing their equivalence in the (13)C((1)H) NMR spectra.

PMID- 12793836
TI  - Intranasal diamorphine as an alternative to intramuscular morphine:
      pharmacokinetic and pharmacodynamic aspects.
AB  - Diamorphine is a semisynthetic derivative of morphine that is currently licensed
      for use in the treatment of moderate to severe acute pain, administered by the
      intramuscular, intravenous or subcutaneous routes. It is highly water-soluble and
      has a number of properties that render it suitable for administration via the
      nasal route. Administration via the intranasal route is well described for other
      drugs, but has only recently been evaluated in a clinical setting for
      diamorphine. A well-tolerated and rapidly effective analgesic agent has proven
      elusive in the paediatric setting. The pharmacokinetic profile of intranasal
      diamorphine in adults has been systematically studied. It is rapidly and dose
      dependently absorbed as a dry powder, with peak plasma concentrations occurring
      within 5 minutes, and has a similar pharmacokinetic profile to that of
      intramuscular diamorphine. It is rapidly converted to 6-acetylmorphine (peak
      concentrations within 5-10 minutes) and thence to morphine (peak concentrations
      within 1 hour). The pharmacodynamic properties of intranasal diamorphine have
      also been studied in comparison with intramuscular diamorphine. Intranasal and
      intramuscular administration of diamorphine resulted in similar physiological
      responses (including pupil diameter, respiration rate and temperature). Changes
      in behavioural measures (including euphoria, sedation and dysphoria) were also
      similar. Intranasal administration of diamorphine, therefore, produces the
      expected drug effects on the same timescale and of the same magnitude as
      intramuscular injection. Intranasal diamorphine has been clinically evaluated in
      a randomised controlled trial versus intramuscular morphine in the setting of
      acute orthopaedic pain in children with fractures. Intranasal diamorphine
      provided the same overall degree of pain relief as intramuscular morphine, but
      with a quicker onset of action. It was found to be well tolerated with an
      acceptable safety profile. It has also been studied in the setting of patient
      controlled analgesia for postoperative pain in adults, with encouraging results.
      The pharmacokinetic and pharmacodynamic properties of intranasal diamorphine, and
      particularly the ability to administer it without a needle (and therefore reduce
      the incidence of transmissible infection), have made this a popular route for
      abuse amongst opioid addicts. In this setting, however, the intranasal route is
      not free from adverse events, including deaths. The primary clinical need in the
      paediatric population is for a well tolerated, effective and expedient analgesic
      agent that is safe to use; intranasal diamorphine has pharmacokinetic properties
      that would make it suitable for such a clinical indication and, in clinical
      evaluations to date, appears to be promising.

PMID- 12793837
TI  - Metabolic stability for drug discovery and development: pharmacokinetic and
      biochemical challenges.
AB  - Metabolic stability refers to the susceptibility of compounds to
      biotransformation in the context of selecting and/or designing drugs with
      favourable pharmacokinetic properties. Metabolic stability results are usually
      reported as measures of intrinsic clearance, from which secondary pharmacokinetic
      parameters such as bioavailability and half-life can be calculated when other
      data on volume of distribution and fraction absorbed are available. Since these
      parameters are very important in defining the pharmacological and toxicological
      profile of drugs as well as patient compliance, the pharmaceutical industry has a
      particular interest in optimising for metabolic stability during the drug
      discovery and development process. In the early phases of drug discovery, new
      chemical entities cannot be administered to humans; hence, predictions of these
      properties have to be made from in vivo animal, in vitro cellular/subcellular and
      computational systems. The utility of these systems to define the metabolic
      stability of compounds that is predictive of the human situation will be reviewed
      here. The timing of performing the studies in the discovery process and the
      impact of recent advances in research on drug absorption, distribution,
      metabolism and excretion (ADME) will be evaluated with respect to the scope and
      depth of metabolic stability issues. Quantitative prediction of in vivo clearance
      from in vitro metabolism data has, for many compounds, been shown to be poor in
      retrospective studies. One explanation for this may be that there are components
      used in the equations for scaling that are missing or uncertain and should be an
      area of more research. For example, as a result of increased biochemical
      understanding of drug metabolism, old assumptions (e.g. that the liver is the
      principal site of first-pass metabolism) need revision and new knowledge (e.g.
      the relationship between transporters and drug metabolising enzymes) needs to be
      incorporated into in vitro-in vivo correlation models. With ADME parameters
      increasingly being determined on automated platforms, instead of using results
      from high throughput screening (HTS) campaigns as simple go/no-go filters, the
      time saved and the many compounds analysed using the robots should be invested in
      careful processing of the data. A logical step would be to investigate the
      potential to construct computational models to understand the factors governing
      metabolic stability. A rational approach to the use of HTS assays should aim to
      screen for many properties (e.g. physicochemical parameters, absorption,
      metabolism, protein binding, pharmacokinetics in animals and pharmacology) in an
      integrated manner rather than screen against one property on many compounds,
      since it is likely that the final drug will represent a global average of these
      properties.

PMID- 12793838
TI  - Deposition and effects of inhaled corticosteroids.
AB  - Inhaled corticosteroids are now recommended as maintenance therapy for all but
      the mildest cases of asthma, and may be delivered by a variety of devices and
      formulations. Drug delivery may be assessed by both in vitro and in vivo methods.
      Although drug deposition in the lungs is expected to predict clinical response,
      this relationship is often masked by the flat nature of corticosteroid dose
      response curves. The effects of inhaled corticosteroids depend not only upon the
      pharmacology of the drug being administered, but also upon its delivery system,
      with more efficient devices not only improving therapeutic effect but also
      potentially increasing systemic adverse effects. Modern delivery systems that
      enhance drug targeting to the lungs make it possible to use lower dosages of
      inhaled corticosteroid, such that the clinical response is maintained but
      systemic exposure reduced.

PMID- 12793839
TI  - Pharmacokinetics of rofecoxib: a specific cyclo-oxygenase-2 inhibitor.
AB  - Rofecoxib is a commonly used specific cyclo-oxygenase-2 (COX-2) inhibitor.
      Rofecoxib has high bioavailability, poor aqueous solubility, an elimination half
      life suitable for daily administration and a volume of distribution approximating
      body mass. Species-specific, predominantly hepatic, metabolism occurs, with novel
      enterohepatic circulation in rats and O-glucuronidation by uridine diphosphate
      glucuronosyl transferase (UGT) 2B7 and 2B15 in human liver microsomes.
      Discrepancies in studies of postoperative analgesia can be putatively explained
      by known pharmacokinetics. Changes in rofecoxib disposition and pharmacokinetics
      are evident between races, in elderly patients, in patients with chronic renal
      insufficiency and in patients with mild to moderate hepatic impairment. Despite
      the selective action of COX-2 inhibitors, there remains the potential for
      significant drug interactions. Rofecoxib has been shown to have interactions with
      rifampicin (rifampin), warfarin, lithium and angiotensin converting enzyme (ACE)
      inhibitors and theophylline. COX-2 inhibitors represent a major therapeutic
      advance in terms of gastrointestinal safety; however, long-term safety in other
      organ systems and with concomitant drug administration still remain to be proven.

PMID- 12793841
TI  - Pharmacokinetic and pharmacodynamic studies of SK-896, a new human motilin
      analogue, in healthy male volunteers.
AB  - OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of SK-896
      ([Leu(13)]motilin-Hse) after intravenous administration to healthy male
      volunteers. DESIGN AND SETTING: This was a non-blinded phase I study.
      PARTICIPANTS: Thirty male Japanese volunteers (mean age 30.6 years) participated
      in this study. The volunteers were divided into five groups receiving different
      doses of SK-896. METHODS: The pharmacokinetics and pharmacodynamics of SK-896
      were evaluated after single intravenous infusions of doses of 10, 20, 40 and 80
      micro g over 20 minutes to fasting volunteers, or after multiple intravenous
      infusions (twice a day for 3 days) of doses of 40 micro g over 20 minutes to
      volunteers in the morning (fasting) and afternoon (non-fasting). Plasma
      concentrations of immunoreactive SK-896 were determined by radioimmunoassay, and
      borborygmus was measured as an indicator of drug effect (acceleration of
      gastrointestinal motility) with an improved Holter electrocardiograph attached to
      the abdomen. RESULTS: When SK-896 was given by single intravenous infusion at
      each dose, the plasma concentration of immunoreactive SK-896 rapidly increased to
      a maximum at the end of the infusion. After the infusion was completed, plasma
      concentrations declined monoexponentially with an elimination half-time of 4.57
      5.64 minutes. The area under the concentration-time curve and the maximum
      concentration (1.04-9.08 microg-equiv./L) increased in proportion to the dose,
      and there were no dose-related changes in plasma clearance (7.59-9.34 mL/min/kg),
      mean residence time (7.83-9.51 minutes) or steady-state volume of distribution
      (62.9-73.9 mL/kg), indicating that SK-896 plasma concentrations can be described
      by a linear pharmacokinetic model within the dose range of the present study.
      After beginning administration, an increase in borborygmus was observed. At doses
      of 40 and 80 micro g, the borborygmus did not continue even when the plasma
      concentration was maintained, suggesting that tachyphylaxis occurs at a higher
      dose. When SK-896 was given as multiple intravenous infusions, the
      pharmacokinetics did not change with repeated administration. The intensity of
      borborygmus was low with afternoon administration, reaching only one-third to one
      half that with morning administration, suggesting that, like native motilin, SK
      896 does not stimulate gastrointestinal motility in the non-fasting state.
      CONCLUSIONS: The appropriate dose and administration period (fasting or non
      fasting) are important factors in stimulating and maintaining gastrointestinal
      motility when treating gastroparalysis with SK-896.

PMID- 12793842
TI  - A revised pharmacokinetic model for alcohol.
AB  - OBJECTIVE: To correct a defect in widely utilised pharmacokinetic models of
      alcohol absorption into the blood. METHODS: The implications of the defect are
      briefly described. A highly simplified model that corrects this defect is then
      proposed, and the resulting differential equation describing blood-alcohol
      concentration from ingestion to elimination is derived. The equation is solved in
      closed form. RESULTS: The improved model assumes that diffusion of alcohol across
      the interface between the stomach/intestine complex and the remaining body fluids
      (including blood plasma) is linearly proportional to the difference in alcohol
      concentration across the interface. The resulting equation is tested against
      experimental data with excellent agreement. CONCLUSIONS: This model enables
      inferences to be drawn that are not possible with the more conventional model.

PMID- 12793840
TI  - Pharmacokinetics of the dietary supplement creatine.
AB  - Creatine is a nonessential dietary component that, when supplemented in the diet,
      has shown physiological benefits in athletes, in animal-based models of disease
      and in patients with various muscle, neurological and neuromuscular disease. The
      clinical relevance of creatine supplementation is based primarily on its role in
      ATP generation, and cells may be able to better handle rapidly changing energy
      demands with supplementation. Although the pharmacological outcome measures of
      creatine have been investigated, the behaviour of creatine in the blood and
      muscle is still not fully understood. Creatine is most probably actively absorbed
      from the gastrointestinal tract in a similar way to amino acids and peptides. The
      distribution of creatine throughout the body is largely determined by the
      presence of creatine transporters. These transporters not only serve to
      distribute creatine but serve as a clearance mechanism because of creatine
      'trapping' by skeletal muscle. Besides the pseudo-irreversible uptake by skeletal
      muscle, creatine clearance also depends on renal elimination and degradation to
      creatinine. Evidence suggests that creatine pharmacokinetics are nonlinear with
      respect to dose size and frequency. Skeletal muscle, the largest depot of
      creatine, has a finite capacity to store creatine. As such, when these stores are
      saturated, both volume of distribution and clearance can decrease, thus leading
      to complex pharmacokinetic situations. Additionally, other dietary components
      such as caffeine and carbohydrate can potentially affect pharmacokinetics by
      their influence on the creatine transporter. Disease and age may also affect the
      pharmacokinetics, but more information is needed. Overall, there are very limited
      pharmacokinetic data available for creatine, and further studies are needed to
      define absorption characteristics, clearance kinetics and the effect of multiple
      doses. Additionally, the relationship between plasma creatine and muscle creatine
      needs to be elucidated to optimise administration regimens.

PMID- 12793843
TI  - Pharmacokinetics and pharmacodynamics of intravenous levofloxacin in patients
      with early-onset ventilator-associated pneumonia.
AB  - OBJECTIVE: To investigate the pharmacokinetics of levofloxacin and the
      pharmacokinetic-pharmacodynamic appropriateness of its total body exposure in
      patients in the intensive care unit (ICU) treated for early-onset ventilator
      associated pneumonia (VAP) with intravenous levofloxacin 500mg twice daily.
      DESIGN: Prospective non-blinded pharmacokinetic-pharmacodynamic study.
      PARTICIPANTS: Ten critically ill adult patients with normal renal function.
      METHODS: Blood and urine samples were collected at appropriate times during a 12
      hour administration interval at steady state. Levofloxacin concentrations were
      determined by high-performance liquid chromatography. Clinical and
      microbiological outcomes were assessed. RESULTS: Levofloxacin pharmacokinetics
      were only partially comparable with those obtained from literature data for
      healthy volunteers. Area under the concentration-time curve (AUC(tau)) over the
      12-hour dosage interval was about 30-40% lower than in healthy volunteers (33.90
      vs 49.60 mg. h/L). The reduced exposure may be due to a greater clearance of
      levofloxacin (0.204 vs 0.145 L/h/kg [3.40 vs 2.42 mL/min/kg]), leading to a
      shorter elimination half-life (5.2 vs 7.6 hours). Cumulative urinary excretion
      during the 12-hour dosage interval confirmed the greater excretion of unchanged
      drug in these patients compared with healthy subjects (76% vs 68%).
      Coadministered drugs used to treat underlying diseases (dopamine, furosemide,
      mannitol) may at least partially account for this enhanced elimination in
      critically ill patients. Intravenous levofloxacin 500mg twice daily ensured a
      median C(max)/MIC (maximum plasma concentration/minimum inhibitory concentration)
      ratio of 102 and a median 24-hour AUC/MIC ratio of 930 SIT(-1). h (inverse serum
      inhibitory titre integrated over time) against methicillin-sensitive
      Staphylococcus aureus and Haemophilus influenzae. The overall success rate of the
      assessable cases was 75% (6/8). Bacterial eradication was obtained in all of the
      assessable cases (8/8), but a superinfection (Acinetobacter anitratus,Pseudomonas
      aeruginosa) occurred in three cases. CONCLUSIONS: The findings support the
      suitability of intravenous levofloxacin 500mg twice daily in the treatment of
      early-onset VAP in ICU patients with normal renal function. Levofloxacin may
      represent a valid alternative to non-pseudomonal beta-lactams or aminoglycosides
      in the empirical treatment of early-onset VAP. However, further larger studies
      are warranted to investigate its efficacy.

PMID- 12793844
TI  - Low nevirapine plasma concentrations predict virological failure in an unselected
      HIV-1-infected population.
AB  - OBJECTIVE: To assess the relationship between plasma nevirapine concentrations
      and plasma HIV-1 RNA response in HIV-1-infected patients. DESIGN: An
      observational cohort analysis. METHODS: Plasma samples were obtained on a routine
      basis from 189 patients receiving nevirapine 200mg twice daily, and plasma
      nevirapine concentrations were measured with reversed phase high performance
      liquid chromatography. Patients were divided into two groups based on plasma
      nevirapine concentrations below (and equal to) or above 3 mg/L. The association
      between steady-state nevirapine concentrations and plasma HIV-1 RNA was
      determined by multivariate analysis. RESULTS: Out of 189 patients, 13 (7%) had
      low nevirapine plasma concentrations and 176 patients had concentrations above 3
      mg/L. In total, 22 (12%) patients showed virological failure and 8 patients (4%)
      discontinued nevirapine because of adverse effects. The risk of failure in
      patients with nevirapine plasma concentrations </=3mg/L was increased (relative
      risk 5.0, 95% CI 1.8-13.7). Rashes and liver enzyme elevations each occurred in
      8% of patients. CONCLUSIONS: Low nevirapine drug concentrations are predictive of
      virological failure.

PMID- 12793855
TI  - Statins and their role in vascular protection.
AB  - The statins reduce cholesterol synthesis through inhibition of HMG-CoA (3-hydroxy
      3-methylglutaryl-CoA) reductase and are widely prescribed for hyperlipidaemia to
      reduce the risk of atherosclerotic complications. The beneficial effect of lipid
      lowering by statins in the treatment of coronary heart disease has been
      demonstrated in large clinical trials. However, statins appear to have additional
      benefits on vascular function above and beyond their lipid lowering effects.
      Through inhibition of L-mevalonate synthesis, statins also prevent the synthesis
      of isoprenoid intermediates, including farnesylpyrophosphate and
      geranylgeranylpyrophosphate. Isoprenylation is important in the post
      translational modification of a variety of proteins, including the small GTPases
      Rho, Rac and Ras, and hence plays an integral role in cellular signalling.
      Moreover, interference with isoprenylation underlies many of the beneficial
      actions of the statins on vascular endothelium, which include increased
      endothelial nitric oxide synthase expression, pro-angiogenic effects, increased
      fibrinolytic activity, immunomodulatory and anti-inflammatory actions, including
      increased resistance to complement. This has led to interest in the use of this
      class of drugs outside the realm of cardiovascular disease.

PMID- 12793856
TI  - Increased tissue protein synthesis during spontaneous inflammatory bowel disease
      in HLA-B27 rats.
AB  - Inflammatory bowel diseases (IBDs) are associated with an increased whole-body
      protein turnover. In certain drug-induced experimental models of IBD,
      disturbances of protein synthesis in tissues have been reported recently, but it
      is unclear if similar disturbances occur in other chronic intestinal diseases.
      Therefore we investigated changes in protein synthesis in different tissues of
      HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously
      chronic inflammation, with major involvement of the colon. Protein synthesis rate
      in HLA-B27 rats was shown to be higher in nine different tissues compared with
      control (Fisher 344) rats. The absolute rate of protein synthesis was highly
      stimulated at the main inflammatory site (+290% in the colon). However, liver,
      muscle and skin appeared to be major contributors to the increased protein
      synthesis observed at the whole-body level. Despite the increased protein
      synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an
      increased proteolysis. These results contrast with metabolic disturbances
      described in acute inflammation and colitis induced by drugs (i.e. dextran sodium
      sulphate). The present study suggests that the modifications of protein
      metabolism are strongly influenced by the type of the inflammatory diseases and
      thus by the underlying mechanisms, which result in different metabolic
      adaptations and specific nutritional requirements.

PMID- 12793858
TI  - 5,10-methenyltetrahydrofolate cyclohydrolase, rat liver and chemically catalysed
      formation of 5-formyltetrahydrofolate.
AB  - The 5,10-methenyltetrahydrofolate (5,10-CH=H4folate) synthetase catalyses the
      physiologically irreversible formation of 5,10-CH=H4folate from 5
      formyltetrahydrofolate (5-HCO-H4folate) and ATP. It is not clear how (or if) 5
      HCO-H4folate is formed in vivo. Using a spectrophotometric assay for 5-HCO
      H4folate, human recombinant 5,10-CH=H4folate cyclohydrolase, which catalyses the
      hydrolysis of 5,10-CH=H4folate to 10-HCO-H4folate, was previously shown to
      catalyse inefficiently the formation of 5-HCO-H4folate at pH 7.3 [Pelletier and
      MacKenzie (1996) Bioorg. Chem. 24, 220-228]. In the present study, we report that
      (i) the human cyclohydrolase enzyme catalyses the conversion of 10-HCO-/5,10
      CH=H4folate into 5-HCO-H4folate (it is also chemically formed) at pH 4.0-7.0;
      (ii) rat liver has a very low capacity to catalyse the formation of 5-HCO
      H4folate when compared with the traditional activity of 5,10-CH=H4folate
      cyclohydrolase and the activity of the 5,10-CH=H4folate synthetase; and (iii) a
      substantial amount of 5-HCO-H4folate reported to be present in rat liver is
      chemically formed during analytical procedures. We conclude that (i) the
      cyclohydrolase represents some of the capacity of rat liver to catalyse the
      formation of 5-HCO-H4folate; (ii) the amount of 5-HCO-H4folate reported to be
      present in rat liver is overestimated (liver 5-HCO-H4folate content may be
      negligible); and (iii) there is little evidence that 5-HCO-H4folate inhibits one
      carbon metabolism in mammals.

PMID- 12793857
TI  - Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human
      colorectal cancer cells.
AB  - Naproxen, sulindac and salicylate, three NSAIDs (non-steroidal anti-inflammatory
      drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was
      accompanied by significant depletion of intracellular polyamine content.
      Inhibition of ornithine decarboxylase (the first enzyme of the polyamine
      biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine
      N(1)-acetyltransferase (the enzymes responsible for polyamine catabolism) and
      induction of polyamine export all contributed to the decreased intracellular
      polyamine content. Morphological examination of the cells showed typical signs of
      apoptosis, and this was confirmed by DNA fragmentation and measurement of caspase
      3-like activity. Re-addition of spermidine to the cells partially prevented
      apoptosis and recovered the cell number. Thus polyamines appear to be an integral
      part of the signalling pathway mediating NSAID toxicity in human colorectal
      cancer cells, and may therefore also be important in cancer chemoprevention in
      humans.

PMID- 12793859
TI  - Enhancement of nisin production by Lactococcus lactis in periodically re
      alkalized cultures.
AB  - Synthesis of nisin as well as biomass production by Lactococcus lactis subsp.
      lactis CECT (Coleccion Espanola de Cultivos Tipo) 539 on both hydrolysed mussel
      processing waste and whey medium were followed in three fixed volume fed-batch
      fermentations, with re-alkalization cycles. The two cultures on mussel-processing
      waste (MPW) were fed with a 240 g/l concentrated glucose and with a concentrated
      MPW (about 100 g of glucose/l). The culture on whey was fed with a mixture of
      concentrated whey (48 g of total sugars/l) and a 400 g/l concentrated lactose.
      The three cultures were mainly characterized with higher nisin titres [49.7,
      109.6 and 124.7 bacteriocin activity units (AU)/ml respectively] compared with
      the batch process on de Man, Rogosa and Sharpe [(1960) J. Appl. Bacteriol. 23,
      130-135] medium (49.6 AU/ml), MPW (9.5 AU/ml) and whey (22.5 AU/ml) [1 AU/ml is
      the amount of antibacterial compound needed to obtain 50% growth inhibition
      (LD50) compared with control tubes]. In the three fed-batch cultures a shift from
      homolactic to mixed-acid fermentation was observed, and other products (acetic
      acid, butane-2,3-diol or ethanol) in addition to lactic acid were detectable in
      the medium. However, their contributions to the total antibacterial activity of
      the post-incubates (the cell-free culture supernatant obtained at the end of the
      fermentation process) of L. lactis CECT 539 against Carnobacterium piscicola CECT
      4020 were very low.

PMID- 12793860
TI  - Optimization of submerged-culture conditions for mycelial growth and exo
      biopolymer production by Auricularia polytricha (wood ears fungus) using the
      methods of uniform design and regression analysis.
AB  - This paper is concerned with the optimization of submerged culture conditions for
      mycelial growth and exo-biopolymer production by Auricularia polytricha by one
      factor-at-a-time and uniform design (UD) methods. First, the one-factor-at-a-time
      method was adopted to investigate the effects of environmental factors (i.e.,
      initial pH and temperature) and variables of medium components (i.e., carbon,
      nitrogen and mineral sources) on mycelial growth and exo-biopolymer production.
      Sucrose, yeast extract, and K2HPO4 were identified to be the most suitable
      carbon, nitrogen, and mineral sources, respectively. The optimal temperature and
      initial pH for mycelial growth and exo-biopolymer production were found to be 25
      degrees C and 5.0, respectively. Subsequently, the concentrations of sucrose,
      yeast extract, and K2HPO4 were optimized using the UD method. The optimal
      concentrations for the enhanced production were determined as 6% (w/v) sucrose,
      2.5% (w/v) yeast extract, and 0.3% (w/v) K2HPO4 for mycelial yield, and 6% (w/v)
      sucrose, 1.28% (w/v) yeast extract, and 0.3% (w/v) K2HPO4 for exo-biopolymer
      production, respectively. Subsequent experiments confirmed the validity of the
      models. This optimization strategy in shake-flask culture led to a mycelial yield
      of 6.14 g/l, and exo-biopolymer production of 2.12 g/l, respectively, which were
      considerably higher than those obtained in the preliminary studies. By using the
      optimized medium, the maximum concentrations of mycelial biomass and exo
      biopolymer in a 5 litre stirred-tank bioreactor indicated 35.3 g/l and 3.1 g/l,
      respectively.

PMID- 12793861
TI  - Nucleoside diphosphate kinase-like activity in adenylate kinase of Mycobacterium
      tuberculosis.
AB  - Ak (adenylate kinase) is a ubiquitous enzyme that catalyses a reversible high
      energy phosphoryl-transfer reaction between ATP and AMP to form ADP. In the
      present study, the Ak gene (adk) of Mycobacterium tuberculosis was cloned,
      expressed in Escherichia coli and purified as a glutathione S-transferase fusion
      protein. Purified Ak converted AMP into ADP in the presence of [gamma-32P]ATP or
      [gamma-32P]GTP. Replacement of arginine-88 of adk with glycine resulted in the
      loss of enzymic activity. The purified protein also showed Ndk (nucleoside
      diphosphate kinase)-like activity as it transferred terminal phosphate from
      [gamma-32P]ATP to all nucleoside diphosphates, converting them into corresponding
      triphosphates. However, Ndk-like activity of Ak was not observed with [gamma
      32P]GTP. Immunoblot analysis of various cellular fractions of M. tuberculosis
      H37Rv revealed that Ak is a cytoplasmic protein. The dual activity of Ak as both
      nucleoside mono- and di-phosphate kinases suggested that this enzyme may have a
      role in RNA and DNA biosynthesis in addition to its role in intracellular
      nucleotide metabolism.

PMID- 12793863
TI  - Perioperative optimization and right heart catheterization: what technique in
      which patient?

PMID- 12793864
TI  - Selective decontamination of the digestive tract: all questions answered?

PMID- 12793865
TI  - Prokinetic agents in critical care.

PMID- 12793866
TI  - Mechanisms of ventilator-induced lung injury: the clinician's perspective.

PMID- 12793867
TI  - Variation in sepsis care: a wake-up call.

PMID- 12793868
TI  - Recently published papers: small pieces of the puzzle and the long-term view.

PMID- 12793869
TI  - The role of teams in resolving moral distress in intensive care unit decision
      making.

PMID- 12793870
TI  - Closing the gap on unmeasured anions.

PMID- 12793871
TI  - Clinical review: fever in intensive care unit patients.
AB  - Fever is a common response to sepsis in critically ill patients. Fever occurs
      when either exogenous or endogenous pyrogens affect the synthesis of
      prostaglandin E2 in the pre-optic nucleus. Prostaglandin E2 slows the rate of
      firing of warm sensitive neurons and results in increased body temperature. The
      febrile response is well preserved across the animal kingdom, and experimental
      evidence suggests it may be a beneficial response to infection. Fever, however,
      is commonly treated in critically ill patients, usually with antipyretics,
      without good data to support such a practice. Fever induces the production of
      heat shock proteins (HSPs), a class of proteins critical for cellular survival
      during stress. HSPs act as molecular chaperones, and new data suggest they may
      also have an anti-inflammatory role. HSPs and the heat shock response appear to
      inhibit the activation of NF-kappabeta, thus decreasing the levels of
      proinflammatory cytokines. The anti-inflammatory effects of HSPs, coupled with
      improved survival of animal models with fever and infection, call into question
      the routine practice of treating fever in critically ill patients.

PMID- 12793872
TI  - Bench-to-bedside review: severe lactic acidosis in HIV patients treated with
      nucleoside analogue reverse transcriptase inhibitors.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are effective antiretroviral
      therapy for the treatment of HIV-infected patients. NRTIs can induce
      mitochondrial impairment that leads to a number of adverse events, including
      symptomatic lactic acidosis. In the present review, we describe the underlying
      mechanism of NRTI-induced toxicity and the main clinical features of this
      infrequent, but severe, emerging complication. We also summarise experimental
      data and clinical observations that support the use of L-carnitine
      supplementation to reverse NRTI-induced mitochondrial impairment.

PMID- 12793874
TI  - Science review: mechanisms of ventilator-induced injury.
AB  - Acute respiratory distress syndrome (ARDS) and acute lung injury are among the
      most frequent reasons for intensive care unit admission, accounting for
      approximately one-third of admissions. Mortality from ARDS has been estimated as
      high as 70% in some studies. Until recently, however, no targeted therapy had
      been found to improve patient outcome, including mortality. With the completion
      of the National Institutes of Health-sponsored Acute Respiratory Distress
      Syndrome Network low tidal volume study, clinicians now have convincing evidence
      that ventilation with tidal volumes lower than those conventionally used in this
      patient population reduces the relative risk of mortality by 21%. These data
      confirm the long-held suspicion that the role of mechanical ventilation for acute
      hypoxemic respiratory failure is more than supportive, in that mechanical
      ventilation can also actively contribute to lung injury. The mechanisms of the
      protective effects of low tidal volume ventilation in conjunction with positive
      end expiratory pressure are incompletely understood and are the focus of ongoing
      studies. The objective of the present article is to review the potential cellular
      mechanisms of lung injury attributable to mechanical ventilation in patients with
      ARDS and acute lung injury.

PMID- 12793875
TI  - Intramucosal-arterial PCO2 gap does reflect tissue dysoxia.

PMID- 12793877
TI  - Passive leg elevation and head-down tilt: effects and duration of changes.

PMID- 12793879
TI  - The PIRO concept: P is for predisposition.

PMID- 12793880
TI  - The PIRO concept: I is for infection.

PMID- 12793881
TI  - The PIRO concept: R is for response.

PMID- 12793882
TI  - The PIRO concept: O is for organ dysfunction.

PMID- 12793883
TI  - Case report: severe mercuric sulphate poisoning treated with 2,3
      dimercaptopropane-1-sulphonate and haemodiafiltration.
AB  - INTRODUCTION: Inorganic mercury poisoning is uncommon, but when it occurs it can
      result in severe, life-threatening features and acute renal failure. Previous
      reports on the use of extracorporeal procedures such as haemodialysis and
      haemoperfusion have shown no significant removal of mercury. We report here the
      successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS),
      together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient
      with severe inorganic mercury poisoning. CASE REPORT: A 40-year-old man presented
      with haematemesis after ingestion of 1 g mercuric sulphate and rapidly
      deteriorated in the emergency department, requiring intubation and ventilation.
      His initial blood mercury was 15 580 microg/l. At 4.5 hours after ingestion he
      was started on DMPS. He rapidly developed acute renal failure and so he was
      started on CVVHDF for renal support and in an attempt to improve mercury
      clearance; CVVHDF was continued for 14 days. METHODS: Regular ultradialysate and
      pre- and post-filtrate blood samples were taken and in addition all
      ultradialysate generated was collected to determine its mercury content. RESULTS:
      The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the
      ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at
      210-hours after ingestion. He developed no neurological features and was
      discharged from hospital on day 50. Five months after discharge from hospital he
      remained asymptomatic, with normal creatinine clearance. DISCUSSION: We describe
      a patient with severe inorganic mercury poisoning in whom full recovery occurred
      with the early use of the chelating agent DMPS and CVVHDF. There was removal of a
      significant amount of mercury by CVVHDF. CONCLUSION: We feel that CVVHDF should
      be considered in patients with inorganic mercury poisoning, particularly those
      who develop acute renal failure, together with meticulous supportive care and
      adequate doses of chelation therapy with DMPS.

PMID- 12793884
TI  - Multivariate analysis of risk factors for QT prolongation following subarachnoid
      hemorrhage.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) often causes a prolongation of the
      corrected QT (QTc) interval during the acute phase. The aim of the present study
      was to examine independent risk factors for QTc prolongation in patients with SAH
      by means of multivariate analysis. METHOD: We studied 100 patients who were
      admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography
      (ECG) was performed immediately after admission. QT intervals were measured from
      the ECG and were corrected for heart rate using the Bazett formula. We measured
      serum levels of sodium, potassium, calcium, adrenaline (epinephrine),
      noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose.
      RESULTS: The average QTc interval was 466 +/- 46 ms. Patients were categorized
      into two groups based on the QTc interval, with a cutoff line of 470 ms.
      Univariate analyses showed significant relations between categories of QTc
      interval, and sex and serum concentrations of potassium, calcium, or glucose.
      Multivariate analyses showed that female sex and hypokalemia were independent
      risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was
      associated with a relative risk of 4.53 for severe QTc prolongation as compared
      with normokalemia, while the relative risk associated with female sex was 4.45 as
      compared with male sex. There was a significant inverse correlation between serum
      potassium levels and QTc intervals among female patients. CONCLUSION: These
      findings suggest that female sex and hypokalemia are independent risk factors for
      severe QTc prolongation in patients with SAH.

PMID- 12793885
TI  - The Bair Hugger patient warming system in prolonged vascular surgery: an
      infection risk?
AB  - INTRODUCTION: Use of the Bair Hugger forced-air patient warming system during
      prolonged abdominal vascular surgery may lead to increased bacterial
      contamination of the surgical field by mobilization of the patient's skin flora.
      METHODS: This possibility was studied by analyzing bacterial content in air and
      wound specimens collected during surgery in 16 patients undergoing abdominal
      vascular prosthetic graft insertion procedure, using the Bair Hugger patient
      warming system. The bacterial colony counts from the beginning and the end of
      surgery were compared, and the data analyzed using the Wilcoxon matched pairs
      test. RESULTS: The results showed not only that there was no increase in
      bacterial counts at the study sites, but also that there was a decrease (P <
      0.01) in air bacterial content around the patient and in the operating theatre
      after prolonged use of the patient warmer. No wound or graft infections occurred.
      CONCLUSION: The use of this warming system does not lead to increased bacterial
      contamination of the operating theatre atmosphere, and it is unlikely to affect
      the surgical field adversely.

PMID- 12793886
TI  - Gastric intramucosal pH is stable during titration of positive end-expiratory
      pressure to improve oxygenation in acute respiratory distress syndrome.
AB  - BACKGROUND: Optimal positive end-expiratory pressure (PEEP) is an important
      component of adequate mechanical ventilation in acute lung injury and acute
      respiratory distress syndrome (ARDS). In the present study we tested the effect
      on gastric intramucosal pH of incremental increases in PEEP level (i.e. PEEP
      titration) to improve oxygenation in ARDS. Seventeen consecutive patients with
      ARDS, as defined by consensus criteria, were included in this clinical,
      prospective study. All patients were haemodynamically stable, and were not
      receiving vasopressors. From an initial level of 5 cmH2O, PEEP was titrated at 2
      cmH2O increments until the partial arterial oxygen tension was 300 mmHg or
      greater, peak airway pressure was 45 cmH2O or greater, or mean arterial blood
      pressure decreased by 20% or more of the baseline value. Optimal PEEP was defined
      as the level of PEEP that achieved the best oxygenation. The maximum PEEP was the
      highest PEEP level reached during titration in each patient. RESULTS: Gastric
      mucosal pH was measured using gastric tonometry at all levels of PEEP. The
      thermodilution technique was used for measurement of cardiac index. Gastric
      mucosal pH was similar at baseline and at optimal PEEP levels, but it was
      slightly reduced at maximum PEEP. Cardiac index and oxygen delivery remained
      stable at all PEEP levels. CONCLUSION: Incremental titration of PEEP based on
      improvement in oxygenation does not decrease gastric intramucosal perfusion when
      cardiac output is preserved in patients with ARDS.

PMID- 12793887
TI  - Severe sepsis: variation in resource and therapeutic modality use among academic
      centers.
AB  - BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number
      of discretionary modalities. The objective of the present study was to assess
      intercenter variation in resource and therapeutic modality use in patients with
      severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult
      admissions with severe sepsis from a stratified random sample of patients
      admitted to eight academic tertiary care centers. The main outcome measures were
      length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total
      hospital charges. RESULTS: The adjusted mean total hospital charges varied from
      69 429 dollars to US237 898 dollars across centers, whereas the adjusted LOS
      after onset varied from 15.9 days to 24.2 days per admission. Treatments used
      frequently after the first onset of sepsis among patients with severe sepsis were
      pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support
      (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator
      support and albumin infusion had moderate variation profiles, varying 3.2-fold to
      4.9-fold, whereas the rate of pressor support varied only 1.92-fold across
      centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge
      diagnosis-relative group weight, organ dysfunction and service at onset, the odds
      for using these therapeutic modalities still varied significantly across centers.
      Failure to start antibiotics within 24 hours was strongly correlated with a
      higher probability of 28-day mortality (r2 = 0.72). CONCLUSION: These data
      demonstrate moderate but significant variation in resource use and use of
      technologies in treatment of severe sepsis among academic centers. Delay in
      antibiotic therapy was associated with worse outcome at the center level.

PMID- 12793888
TI  - Erythropoietin mimics the acute phase response in critical illness.
AB  - BACKGROUND: In a prospective observational study, we examined the temporal
      relationships between serum erythropoietin (EPO) levels, haemoglobin
      concentration and the inflammatory response in critically ill patients with and
      without acute renal failure (ARF). PATIENTS AND METHOD: Twenty-five critically
      ill patients, from general and cardiac intensive care units (ICUs) in a
      university hospital, were studied. Eight had ARF and 17 had normal or mildly
      impaired renal function. The comparator group included 82 nonhospitalized
      patients with normal renal function and varying haemoglobin concentrations. In
      the patients, levels of haemoglobin, serum EPO, C-reactive protein, IL-1beta, IL
      6, serum iron, ferritin, vitamin B12 and folate were measured, and Coombs test
      was performed from ICU admission until discharge or death. Concurrent EPO and
      haemoglobin levels were measured in the comparator group. RESULTS: EPO levels
      were initially high in patients with ARF, falling to normal or low levels by day
      3. Thereafter, almost all ICU patients demonstrated normal or low EPO levels
      despite progressive anaemia. IL-6 exhibited a similar initial pattern, but levels
      remained elevated during the chronic phase of critical illness. IL-1beta was
      undetectable. Critically ill patients could not be distinguished from
      nonhospitalized anaemic patients on the basis of EPO levels. CONCLUSION: EPO
      levels are markedly elevated in the initial phase of critical illness with ARF.
      In the chronic phase of critical illness, EPO levels are the same for patients
      with and those without ARF, and cannot be distinguished from noncritically ill
      patients with varying haemoglobin concentrations. Exogenous EPO therapy is
      unlikely to be effective in the first few days of critical illness.

PMID- 12793889
TI  - Conventional or physicochemical approach in intensive care unit patients with
      metabolic acidosis.
AB  - INTRODUCTION: Metabolic acidosis is the most frequent acid-base disorder in the
      intensive care unit. The optimal analysis of the underlying mechanisms is
      unknown. AIM: To compare the conventional approach with the physicochemical
      approach in quantifying complicated metabolic acidosis in patients in the
      intensive care unit. PATIENTS AND METHODS: We included 50 consecutive patients
      with a metabolic acidosis (standard base excess < or = -5). We measured sodium,
      potassium, calcium, magnesium, chloride, lactate, creatinine, urea, phosphate,
      albumin, pH, and arterial carbon dioxide and oxygen tensions in every patient. We
      then calculated HCO3-, the base excess, the anion gap, the albumin-corrected
      anion gap, the apparent strong ion difference, the effective strong ion
      difference and the strong ion gap. RESULTS: Most patients had multiple underlying
      mechanisms explaining the metabolic acidosis. Unmeasured strong anions were
      present in 98%, hyperchloremia was present in 80% and elevated lactate levels
      were present in 62% of patients. Calculation of the anion gap was not useful for
      the detection of hyperlactatemia. There was an excellent relation between the
      strong ion gap and the albumin-corrected and lactate-corrected anion gap (r2 =
      0.934), with a bias of 1.86 and a precision of 0.96. CONCLUSION: Multiple
      underlying mechanisms are present in most intensive care unit patients with a
      metabolic acidosis. These mechanisms are reliably determined by measuring the
      lactate-corrected and albumin-corrected anion gap. Calculation of the more time
      consuming strong ion gap according to Stewart is therefore unnecessary.

PMID- 12793890
TI  - Gastric versus post-pyloric feeding: a systematic review.
AB  - BACKGROUND: Our objective was to evaluate the impact of gastric versus post
      pyloric feeding on the incidence of pneumonia, caloric intake, intensive care
      unit (ICU) length of stay (LOS), and mortality in critically ill and injured ICU
      patients. METHOD: Data sources were Medline, Embase, Healthstar, citation review
      of relevant primary and review articles, personal files, and contact with expert
      informants. From 122 articles screened, nine were identified as prospective
      randomized controlled trials (including a total of 522 patients) that compared
      gastric with post-pyloric feeding, and were included for data extraction.
      Descriptive and outcomes data were extracted from the papers by the two reviewers
      independently. Main outcome measures were the incidence of nosocomial pneumonia,
      average caloric goal achieved, average daily caloric intake, time to the
      initiation of tube feeds, time to goal, ICU LOS, and mortality. The meta-analysis
      was performed using the random effects model. RESULTS: Only medical,
      neurosurgical and trauma patents were enrolled in the studies analyzed. There
      were no significant differences in the incidence of pneumonia, percentage of
      caloric goal achieved, mean total caloric intake, ICU LOS, or mortality between
      gastric and post-pyloric feeding groups. The time to initiation of enteral
      nutrition was significantly less in those patients randomized to gastric feeding.
      However, time to reach caloric goal did not differ between groups. CONCLUSION: In
      this meta-analysis we were unable to demonstrate a clinical benefit from post
      pyloric versus gastric tube feeding in a mixed group of critically ill patients,
      including medical, neurosurgical, and trauma ICU patients. The incidences of
      pneumonia, ICU LOS, and mortality were similar between groups. Because of the
      delay in achieving post-pyloric intubation, gastric feeding was initiated
      significantly sooner than was post-pyloric feeding. The present study, while
      providing the best current evidence regarding routes of enteral nutrition, is
      limited by the small total sample size.

PMID- 12793891
TI  - Familial breast cancer and the hCHK2 1100delC mutation: assessing cancer risk.
AB  - Germline mutations in the human checkpoint gene, hCHK2, were first identified in
      1999 in cases of Li-Fraumeni syndrome. Recent studies have demonstrated that the
      hCHK2 1100delC mutation acts as a low-penetrance tumour suppressor gene in
      familial breast cancer not associated with mutations in BRCA1 or BRCA2. The
      present article describes the published studies on hCHK2 1100delC and addresses
      some of the key questions raised.

PMID- 12793892
TI  - Expanding the therapeutic repertoire of epidermal growth factor receptor
      blockade: radiosensitization.
AB  - Expression of epidermal growth factor receptor (EGFR) has been associated with
      radioresistance in cancer. Moreover, tumour cell recovery after irradiation
      paradoxically occurs, in part, as a result of activation of EGFR signalling by
      such treatment. A recent article by Huang, Li, Armstrong and Harari provides
      strong rationale for considering the anti-EGFR agent ZD1839 ('Iressa') as a
      radiosensitizing strategy. With the use of several in vitro and xenograft models
      of human squamous cell head and neck carcinoma, ZD1939 was shown to markedly
      improve radiotherapeutic response, with superior tumour inhibition and delayed
      tumour regrowth. Mechanisms underlying this effect included anti-proliferative
      and pro-apoptotic activity, with significant perturbation of tumour angiogenesis.

PMID- 12793893
TI  - Host microenvironment in breast cancer development: extracellular matrix-stromal
      cell contribution to neoplastic phenotype of epithelial cells in the breast.
AB  - Epithelial-mesenchymal interactions play an important role both in normal mammary
      gland development and during neoplastic transformation. Perturbations in the
      production, deposition and degradation of the extracellular matrix occurring
      during neoplastic transformation and progression have been implicated to arise
      from alterations in the stromal response. These changes in the stroma exhibit a
      dominant regulatory role, via microenvironmental epigenetic effectors, to
      contribute to the development of the tumorigenic epithelial phenotype. The role
      of stromally derived microenvironmental epigenetic effectors in modulating
      epithelial growth, hormonal response, morphogenesis and epithelial plasticity is
      discussed.

PMID- 12793894
TI  - Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an
      inflammatory breast cancer xenograft model.
AB  - We recently established a new human inflammatory breast cancer (IBC) xenograft
      (WIBC-9) originating from a patient with IBC. The original tumor and WIBC-9
      revealed invasive ductal carcinoma with a hypervascular structure of solid nests
      and marked lymphatic permeation in the overlying dermis. In the central part of
      the solid nests, vasculogenic mimicry, which showed an absence of endothelial
      cells, was observed. Comparison of WIBC-9 with an established non-IBC xenograft
      (MC-5), using time-course dynamic micro-magnetic resonance angiography analysis
      (with a newly developed intravascular macromolecular contrast agent for magnetic
      resonance imaging) demonstrated that the WIBC-9 tumor had blood flow and a
      vascular mimicry-angiogenesis junction.

PMID- 12793895
TI  - Breast cancer-induced angiogenesis: multiple mechanisms and the role of the
      microenvironment.
AB  - Growth and progression of breast cancers are accompanied by increased
      neovascularization (angiogenesis). A variety of factors, including hypoxia and
      genetic changes in the tumor cells, contribute to increased production of
      angiogenic factors. Furthermore, cells within the activated tumor stroma also
      contribute to the increase in production of vascular endothelial growth factor
      and other angiogenic factors, including basic fibroblast growth factor and
      platelet-derived growth factor. The contribution of the microenvironment to tumor
      induced angiogenesis is underscored by findings that breast tumors implanted into
      different tissue sites show marked differences in the extent and nature of the
      angiogenic response. These findings have important implications for designing
      anti-angiogenic therapies.

PMID- 12793896
TI  - 42nd Annual Meeting of the American Society for Cell Biology, San Francisco,
      California, USA, 14-18 December 2002.
AB  - The Annual Meeting of the American Society for Cell Biology (ASCB) is a diverse
      conference covering all topics in cell biology. While all of the basic biology
      presented at this meeting may potentially contribute to breast cancer research,
      there were a significant number of presentations and posters directly pertinent
      to this field. Here we have summarized the research that is of greatest immediate
      relevance to breast cancer, with particular emphasis on mammary gland development
      and tumorigenesis in vivo, three-dimensional in vitro models of mammary
      morphogenesis, alterations of signal transduction pathways in breast cancer, and
      global studies in expression profiling and drug screening.

PMID- 12793897
TI  - The future of cytotoxic therapy: selective cytotoxicity based on biology is the
      key.
AB  - Although mortality from breast cancer is decreasing, 15% or more of all patients
      ultimately develop incurable metastatic disease. It is hoped that new classes of
      target-based cytotoxic therapeutics will significantly improve the outcome for
      these patients. Many of these novel agents have displayed cytotoxic activity in
      preclinical and clinical evaluations, with little toxicity. Such preferential
      cytotoxicity against malignant tissues will remain tantamount to the Holy Grail
      in oncologic therapeutics because this portends improved patient tolerance and
      overall quality of life, and the capacity to deliver combination therapy.
      Combinations of such rationally designed target-based therapies are likely to be
      increasingly important in treating patients with breast carcinoma. The anticancer
      efficacy of these agents will, however, remain dependent on the involvement of
      the targets of these agents in the biology of the individual patient's disease.
      Results of DNA microarray analyses have raised high hopes that the analyses of
      RNA expression levels can successfully predict patient prognosis, and indicate
      that the ability to rapidly 'fingerprint' the oncogenic profile of a patient's
      tumor is now possible. It is hoped that these studies will support the
      identification of the molecules driving a tumor's growth, and the selection of
      the appropriate combination of targeted agents in the near future.

PMID- 12793899
TI  - p27KIP1 phosphorylation by PKB/Akt leads to poor breast cancer prognosis.

PMID- 12793900
TI  - The role of androgens and polymorphisms in the androgen receptor in the
      epidemiology of breast cancer.
AB  - Testosterone binds to the androgen receptor in target tissue to mediate its
      effects. Variations in testosterone levels and androgen receptor activity may
      play a role in the etiology of breast cancer. Here, we review the epidemiologic
      evidence linking endogenous testosterone to breast cancer risk. Paradoxically,
      results from observational studies that have examined polymorphisms in the
      androgen receptor suggest that the low-activity androgen receptor increases
      breast cancer risk. We review the quality of this evidence and conclude with a
      discussion of how the androgen receptor and testosterone results coincide.

PMID- 12793901
TI  - Inflammatory breast cancer: relationship between growth factor signaling and
      motility in aggressive cancers.
AB  - A variety of phenotypic characteristics are required for a cancer cell to
      successfully complete the metastatic cascade. Acquisition of a motile and
      invasive phenotype is one requirement for a cell to become metastatically
      competent. The Rho (Ras homology) GTPases are a subfamily of small GTP-binding
      proteins, which are related to the Ras oncogene. All aspects of cellular motility
      and invasion are controlled by the Rho GTPases and are closely linked to signals
      from the extracellular environment, particularly in response to growth factors.
      Dysregulation of Rho activation through aberrant growth-factor signaling, loss of
      function of key Rho-regulatory proteins or overexpression of Rho mRNA could
      result in increased Rho activity and cellular motility. Therefore, the importance
      of the Rho GTPases in the progression of aggressive cancers, is becoming more
      appreciated.

PMID- 12793902
TI  - Elevated mammaglobin (h-MAM) expression in breast cancer is associated with
      clinical and biological features defining a less aggressive tumour phenotype.
AB  - BACKGROUND: Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells,
      and this feature has been used to detect circulating breast cancer cells and
      occult metastases in sentinel axillary lymph nodes of breast cancer patients.
      However, the biological role of mammaglobin is completely unknown. METHODS: We
      studied 128 fresh-frozen breast cancer specimens by means of reverse
      transcriptase-polymerase chain reaction and quantified their h-MAM mRNA
      expression. This was then correlated with histological and nuclear grade,
      oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53
      expression, as well as with cellular proliferation measured by means of the Ki67
      labelling index, DNA ploidy and S-phase, and finally with the presence or not of
      invaded axillary nodes in the mastectomy specimen. RESULTS: In the univariate
      analysis, high h-MAM expression (above the median for the whole group) correlated
      significantly (P < 0.05) with oestrogen and progesterone receptor expression,
      diploid DNA content, low Ki67 labelling index, low nuclear grade and almost
      significantly (P = 0.058) with the absence of axillary nodal invasion in the
      mastectomy specimen. In a final, multivariate model, only progesterone receptor
      expression, diploid DNA content and absence of nodal invasion were found to be
      independently associated with high h-MAM expression. CONCLUSION: All of the
      features associated with mammaglobin expression reflect, without exception, a
      less aggressive tumour phenotype. Further studies are needed to clarify whether
      this is attributable to h-MAM expression itself, or to another mechanism of which
      mammaglobin expression forms part.

PMID- 12793903
TI  - Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary
      drainage after operations for breast cancer using reverse transcriptase
      polymerase chain reaction.
AB  - BACKGROUND: The diverse biological effects of hepatocyte growth factor/scatter
      factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on
      epithelial cells. Met signaling has a role in normal cellular activities, and may
      be associated with the development and progression of malignant processes. In
      this study we examined whether Met can be detected in the axillary drainage from
      patients who underwent conservative operations for breast cancer, and its
      prognostic significance. METHODS: Thirty-one consecutive patients with invasive
      ductal carcinoma of the breast suitable for breast-conserving treatment were
      studied. The output of the drain that had been placed in the axilla during the
      operation was collected, and the presence of Met and beta-actin were assessed by
      reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were
      compared with the pathological features of the tumor and the axillary lymph
      nodes, and with the estrogen receptor and progesterone receptor status. RESULTS:
      RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of
      the patients. Positive assays were correlated with increasing tumor size and
      grade, with capillary and lymphatic invasion, and with lymph node metastasis (P <
      0.02, for all comparisons). All 12 patients with axillary lymph node metastases
      had positive assays for Met, compared with 57.9% of patients without lymph node
      metastases. All five patients with tumor involvement in the margins of the
      resection had positive assays for Met in their lymphatic fluid, compared with 18
      of 26 positive assays (69.2%) for patients without involved margins (P < 0.04).
      Finally, Met showed negative correlations with positivity for estrogen receptor
      and progesterone receptor (P < 0.02). CONCLUSION: Met can be detected in the
      axillary fluids of patients with breast cancer and its expression in the axillary
      drainage may have potential as a prognostic factor. This finding might be
      relevant to therapeutic considerations, because a positive assay for Met in
      histologically node-negative patients might point to the need to search for node
      microinvasion or involvement of the excision margins with tumor.

PMID- 12793904
TI  - C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism
      and susceptibility to breast cancer.
AB  - BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a
      multifunctional endocytic receptor with an important role in regulating the
      activity of proteinases in extracellular matrix. Several studies have also
      described its role in intracellular signaling. Previous studies showed that the
      expression of LRP1 is related to invasiveness of cancer cells. However, recent
      data on LRP1 suggest that this receptor can also be involved in tumor
      establishment and progression. METHODS: We investigated an association between
      the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a
      sample of women of Caucasian origin. Allele and genotype frequencies of this
      polymorphism were assessed in 164 women with breast cancer and in 183 age
      compatible women without a history of any cancer disease. RESULTS: An increase in
      LRP1 T allele frequency in subjects with breast cancer was observed compared with
      controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with
      the T allele (homozygotes plus heterozygotes) was also observed (odds ratio
      1.743, 95% confidence interval 1.112-2.732). CONCLUSION: The T allele of the
      C766T polymorphism in the LRP1 gene is associated with an increased risk of
      breast cancer development in women of Caucasian origin.

PMID- 12793905
TI  - Erythrocyte membrane fatty acid profile and saturation index in gallbladder
      carcinogenesis: a case-control study.
AB  - BACKGROUND: Gallbladder cancer is a common neoplasm of biliary tract, with an
      unknown etiology. PATIENTS AND METHODS: This study was carried out to evaluate
      the changes in the membrane fatty acid profile and saturation index in patients
      with gallbladder cancer. The study sample consisted of 50 newly diagnosed cases
      of gallbladder cancer and 50 patients undergoing cholecystectomy for
      cholelithiasis were recruited as controls. The fatty acid estimation was carried
      out by high performance liquid chromatography (HPLC). Statistical analysis was
      carried out by student 't' test and one-way ANOVA. Pearson's correlation
      coefficient was also obtained. RESULTS: A significant lowering of erythrocyte
      membrane stearic acid (p = 0.000), arachidonic acid (p = 0.001), and saturation
      index (p = 0.001) was observed in patients with gallbladder cancer compared to
      controls. A significant inverse relation was observed between stearic and oleic
      acid (r = -0.269 p = 0.007). CONCLUSION: Results of the present study suggest an
      increase in the delta 9 desaturation in cancer patients compared to controls
      however, a possible role of biliary stasis due to altered gallbladder motility or
      derangements of signal transduction secondary to altered membrane lipid bilayer
      cannot be ruled out.

PMID- 12793906
TI  - Possible role of membrane gamma-glutamyltransferase activity in the facilitation
      of transferrin-dependent and -independent iron uptake by cancer cells.
AB  - BACKGROUND: The molecular mechanisms by which iron is physiologically transported
      trough the cellular membranes are still only partially understood. Several
      studies indicate that a reduction step of ferric iron to ferrous is necessary,
      both in the case of transferrin-mediated and transferrin-independent iron uptake.
      Recent studies from our laboratory described gamma-glutamyltransferase activity
      (GGT) as a factor capable to effect iron reduction in the cell microenvironment.
      GGT is located on the outer aspect of plasma membrane of most cell types, and is
      often expressed at high levels in malignant tumors and their metastases. The
      present study was aimed at verifying the possibility that GGT-mediated iron
      reduction may participate in the process of cellular iron uptake. RESULTS: Four
      distinct human tumor cell lines, exhibiting different levels of GGT activity,
      were studied. The uptake of transferrin-bound iron was investigated by using 55Fe
      loaded transferrin, as well as by monitoring fluorimetrically the intracellular
      iron levels in calcein-preloaded cells. Transferrin-independent iron uptake was
      investigated using 55Fe complexed by nitrilotriacetic acid (55Fe-NTA complex).The
      stimulation of GGT activity, by administration to cells of the substrates
      glutathione and glycyl-glycine, was generally reflected in a facilitation of
      transferrin-bound iron uptake. The extent of such facilitation was correlated
      with the intrinsic levels of the enzyme present in each cell line. Accordingly,
      inhibition of GGT activity by means of two independent inhibitors, acivicin and
      serine/boric acid complex, resulted in a decreased uptake of transferrin-bound
      iron. With Fe-NTA complex, the inhibitory effect - but not the stimulatory one -
      was also observed. CONCLUSION: It is concluded that membrane GGT can represent a
      facilitating factor in iron uptake by GGT-expressing cancer cells, thus providing
      them with a selective growth advantage over clones that do not possess the
      enzyme.

PMID- 12793907
TI  - Plasma interleukin 8 concentrations in obese subjects with impaired glucose
      tolerance.
AB  - BACKGROUND: Interleukin 8 (IL-8) is a cytokine with atherogenic properties. In
      vitro studies revealed that it is produced and secreted by human adipocytes. We
      recently reported that plasma IL-8 is increased in obese subjects with normal
      glucose tolerance (NGT). The aim of the present study was to measure plasma IL-8
      concentrations in subjects with impaired glucose tolerance (IGT). METHODS: A
      total of 44 subjects with marked overweight or obesity (BMI > 27.8 kg/m2), 27
      with NGT and 17 with IGT, were recruited for the present study. Plasma IL-8
      levels were measured in fasting state, after an oral glucose tolerance test
      (OGTT) and after euglycemic hyperinsulinemic clamp. RESULTS: The studied groups
      did not differ in fasting IL-8 concentrations. Both OGTT and clamp resulted in a
      significant increase in plasma IL-8. The change in IL-8 after clamp was similar
      in both groups. In contrast, after OGTT plasma IL-8 levels (IL-8OGTT) were
      markedly higher in IGT individuals. In IGT, but not NGT group, IL-8OGTT was
      positively related to postload glucose and negatively to insulin sensitivity.
      CONCLUSION: Plasma IL-8 concentrations after glucose load are increased in obese
      IGT subjects in comparison to normoglycemic weight-matched individuals. Increase
      in plasma IL-8 might be both insulin-mediated (during clamp) and glucose-mediated
      (during OGTT).

PMID- 12793908
TI  - Contribution of psychoacoustics and neuroaudiology in revealing correlation of
      mental disorders with central auditory processing disorders.
AB  - BACKGROUND: Psychoacoustics is a fascinating developing field concerned with the
      evaluation of the hearing sensation as an outcome of a sound or speech stimulus.
      Neuroaudiology with electrophysiologic testing, records the electrical activity
      of the auditory pathways, extending from the 8th cranial nerve up to the cortical
      auditory centers as a result of external auditory stimuli. Central Auditory
      Processing Disorders may co-exist with mental disorders and complicate diagnosis
      and outcome. DESIGN: A MEDLINE search was conducted to search for papers
      concerning the association between Central Auditory Processing Disorders and
      mental disorders. The research focused on the diagnostic methods providing the
      inter-connection of various mental disorders and central auditory deficits.
      MEASUREMENTS AND MAIN RESULTS: The medline research revealed 564 papers when
      using the keywords 'auditory deficits' and 'mental disorders'. 79 papers were
      referring specifically to Central Auditory Processing Disorders in connection
      with mental disorders. 175 papers were related to Schizophrenia, 126 to learning
      disabilities, 29 to Parkinson's disease, 88 to dyslexia and 39 to Alzheimer's
      disease. Assessment of the Central Auditory System is carried out through a great
      variety of tests that fall into two main categories: psychoacoustic and
      electrophysiologic testing. Different specialties are involved in the diagnosis
      and management of Central Auditory Processing Disorders as well as the mental
      disorders that may co-exist with them. As a result it is essential that they are
      all aware of the possibilities in diagnostic procedures. CONCLUSIONS:
      Considerable evidence exists that mental disorders may correlate with CAPD and
      this correlation could be revealed through psychoacoustics and neuroaudiology.
      Mental disorders that relate to Central Auditory Processing Disorders are:
      Schizophrenia, attention deficit disorders, Alzheimer's disease, learning
      disabilities, dyslexia, depression, auditory hallucinations, Parkinson's disease,
      alcoholism, anorexia and childhood mental retardation. Clinical awareness should
      be high in order for doctors of the two specialties, psychiatry and
      otorhinolaryngology-audiology to collaborate.

PMID- 12793909
TI  - The potential of electronic medical record systems to support quality improvement
      work and research in Norwegian general practice.
AB  - BACKGROUND: Electronic medical record (EMR) systems are used for many purposes
      including patient care, administration, research, quality improvement and
      reimbursement. This study aimed to test a data extraction tool (QTools) and to
      provide information to support the interpretation of EMR data. METHODS:
      Comparison of aggregated practice data for selected EMR fields and interviews
      with practice staff. Practices received summaries of their data and aggregated
      data for other practices. Summaries were discussed in interviews. RESULTS:
      Fourteen general practices in the Oslo area using the Winmed EMR participated.
      QTools ran successfully at all 14 practices. Nine practices agreed to interviews.
      Apart from age and sex, general patient information was poorly recorded. Face-to
      face consultations account for 59% of contacts but differences in coding led to
      variations between practices. Psychiatric problems accounted for 13% of
      diagnoses, other diagnosis groups rarely accounted for more than 5%. Over 90% of
      diabetics and 75% of patients with heart disease were identified by diagnosis
      code alone. CONCLUSION: Some variation seen in EMR data is due to differences in
      the way staff use their EMR. These data can support quality improvement work but
      this requires an awareness of how the EMR is actually used by practice staff.

PMID- 12793910
TI  - The addition of locust bean gum but not water delayed the gastric emptying rate
      of a nutrient semisolid meal in healthy subjects.
AB  - BACKGROUND: Most of the previous studies regarding the effects of gel-forming
      fibres have considered the gastric emptying of liquid or solid meals after the
      addition of pectin or guar gum. The influence of locust bean gum, on gastric
      emptying of nutrient semisolid meals in humans has been less well studied,
      despite its common occurrence in foods. Using a standardised ultrasound method,
      this study was aimed at investigating if the gastric emptying in healthy subjects
      could be influenced by adding locust been gum, a widely used thickening agent, or
      water directly into a nutrient semisolid test meal. METHODS: The viscosity of a
      basic test meal (300 g rice pudding, 330 kcal) was increased by adding Nestargel
      (6 g, 2.4 kcal), containing viscous dietary fibres (96.5%) provided as seed flour
      of locust bean gum, and decreased by adding 100 ml of water. Gastric emptying of
      these three test meals were evaluated in fifteen healthy non-smoking volunteers,
      using ultrasound measurements of the gastric antral area to estimate the gastric
      emptying rate (GER). RESULTS: The median value of GER with the basic test meal
      (rice pudding) was estimated at 63%, (range 47 to 84%), (the first quartile =
      61%, the third quartile = 69%). Increasing the viscosity of the rice pudding by
      adding Nestargel, resulted in significantly lower gastric emptying rates (p <
      0.01), median GER 54%, (range 7 to 71%), (the first quartile = 48%, the third
      quartile = 60%). When the viscosity of the rice pudding was decreased (basic test
      meal added with water), the difference in median GER 65%, (range 38 to 79%), (the
      first quartile = 56%, the third quartile = 71%) was not significantly different
      (p = 0.28) compared to the GER of the basic test meal. CONCLUSIONS: We conclude
      that the addition of locust bean gum to a nutrient semisolid meal has a major
      impact on gastric emptying by delaying the emptying rate, but that the addition
      of water to this test meal has no influence on gastric emptying in healthy
      subjects.

PMID- 12793911
TI  - In vitro antileishmanial effects of antibacterial diterpenes from two Ethiopian
      Premna species: P. schimperi and P. oligotricha.
AB  - BACKGROUND: Three antibacterial diterpenes: (5R,8R,9S,10R)-12-oxo-ent-3,13(16)
      clerodien-15-oic acid (1), 16-hydroxy-clerod-3,13(14)-diene-15,16-olide (2) and
      ent-12-oxolabda-8,13(16)-dien-15-oic acid (3) were previously isolated form
      Premna schimperi and P. oligotricha. Since andrographolide and other structurally
      related diterpenes were shown to have antileishmanial activity, the aim of the
      present study was to assess the in vitro effect of premna diterpenes against
      Leishmania aethiopica; the causative agent of cutaneous leishmaniasis in
      Ethiopia. RESULTS: The diterpenes showed potent concentration-dependant
      suppressive effect on the viability of axenically cultured amastigotes of L.
      aethiopica. The clerodane diterpenes 1 and 2 were most active (LD50 values 1.08
      and 4.12 microg/ml respectively) followed by andrographolide and 3. Compounds 1
      and 2 appear to be over 20 and 10-times respectively more selective to leishmania
      amastigotes than the permissive host cell line, THP-1 cells or the promastigotes
      stage of the parasites. CONCLUSION: The clerodane diterpenes (1, 2) which were
      more potent and selective than labdanes (andrographolide and 3) are promising for
      further studies and/or development.

PMID- 12793913
TI  - Quality of life of survivors of pediatric intensive care.
AB  - OBJECTIVE: Measuring outcome in pediatric intensive care is necessary to equate
      the high cost of treatment with benefits to the patient. Although mortality rates
      and morbidity are relatively insensitive measures of the benefits of treatment,
      quality of life measurement gives insight into the long-term outcomes. The aim of
      this study was to investigate the long-term quality of life outcome of children
      admitted to a pediatric intensive care unit. DESIGN: Prospective survey. SETTING:
      A 13-bed pediatric intensive care unit in a university-affiliated, tertiary
      referral children's hospital. PATIENTS: Patients were 432 children discharged
      from the pediatric intensive care unit between May 1992 and April 1994.
      INTERVENTIONS: Quality of life was measured by using the Royal Alexandra Hospital
      for Children Measure of Function. The scale has two components, the first part
      completed by the clinician after parent interview and the second part completed
      separately by the parent. MEASUREMENTS AND MAIN RESULTS: Parents of 432 children
      were contacted between 3 and 24 months after discharge. Twenty-seven children
      (6.3%) had died after discharge from the pediatric intensive care unit; 59.3%
      (256) had scores indicating a normal quality of life, and 32.4% (140) had a fair
      quality of life with ongoing health, social, or cognitive problems requiring some
      intervention. Two percent of survivors (nine children) had scores indicating a
      poor quality of life as they had continued to experience significant or disabling
      health problems requiring hospitalization or the equivalent. Predictors of poor
      quality of life included presence of comorbidities, increased length of stay, and
      a diagnostic category of malignancy. Diagnostic categories of respiratory,
      trauma, and cardiac dysfunction were associated with a better outcome.
      CONCLUSIONS: Our results indicate that the long-term outcome in terms of quality
      of life after admission to a pediatric intensive care unit is good or normal for
      the majority of surviving children. Those children with a poor outcome are likely
      to have significant comorbidities or a diagnosis of malignancy.

PMID- 12793912
TI  - Importing statistical measures into Artemis enhances gene identification in the
      Leishmania genome project.
AB  - BACKGROUND: Seattle Biomedical Research Institute (SBRI) as part of the
      Leishmania Genome Network (LGN) is sequencing chromosomes of the trypanosomatid
      protozoan species Leishmania major. At SBRI, chromosomal sequence is annotated
      using a combination of trained and untrained non-consensus gene-prediction
      algorithms with ARTEMIS, an annotation platform with rich and user-friendly
      interfaces. RESULTS: Here we describe a methodology used to import results from
      three different protein-coding gene-prediction algorithms (GLIMMER, TESTCODE and
      GENESCAN) into the ARTEMIS sequence viewer and annotation tool. Comparison of
      these methods, along with the CODONUSAGE algorithm built into ARTEMIS, shows the
      importance of combining methods to more accurately annotate the L. major genomic
      sequence. CONCLUSION: An improvised and powerful tool for gene prediction has
      been developed by importing data from widely-used algorithms into an existing
      annotation platform. This approach is especially fruitful in the Leishmania
      genome project where there is large proportion of novel genes requiring manual
      annotation.

PMID- 12793914
TI  - Heliox versus oxygen for nebulized aerosol therapy in children with lower airway
      obstruction.
AB  - OBJECTIVE: To compare the distribution of an inhaled labeled radioaerosol
      (diethilenotriaminopenthacetate labeled with technetium-99m) when either oxygen
      or heliox was used as a gas vehicle of nebulization. DESIGN: Randomized, double
      blind, controlled study. SETTING: Nuclear medicine imagining department of
      tertiary university-affiliated hospital. PATIENTS: Twenty children (5-15 yrs old)
      with confirmed diagnosis of chronic lower airway obstruction and referred for a
      ventilatory scintigraphy study. INTERVENTION: Patients were randomized to use
      either the heliox mixture (helium/oxygen, 80:20) or oxygen during the
      scintigraphy study. The maximal cumulative irradiation absorbed by the lungs and
      the slope of the curve of the cumulative irradiation incorporated into the lungs
      over the time were used to compare the groups. Student's t -test, one-way
      analysis of variance, chi-square test, and Fisher's exact test were used to
      compare the groups. MEASUREMENTS AND MAIN RESULTS: Ten patients were allocated to
      each group with no differences in demographic data, main diagnosis, and pulmonary
      function tests. Ninety-five percent of the particles produced by both gases had a
      diameter <2.4 micro. The heliox group showed a higher slope of the irradiation
      incorporated curve (p <.05) than the oxygen group. When broken down into groups,
      these changes were more significant in those patients classified by the pulmonary
      function tests as having severe lower airway obstruction. They showed higher
      cumulative lung irradiation (p =.045) and better slope of the irradiation
      incorporated curve (p =.017) when heliox rather than oxygen was used as a vehicle
      for the diethilenotriaminopenthacetate labeled with technetium-99m. Nevertheless,
      in those patients with mild lower airway obstruction, heliox did not show any
      advantage over oxygen in the distribution the radioaerosol into the lungs.
      CONCLUSION: Related to its physical properties, heliox gas seems to have a strong
      and pronounced effect when used in patients with severe lower airway obstruction.
      However, in the absence of severe lower airway obstruction, there is no advantage
      to using heliox instead of oxygen as a vehicle of nebulization.

PMID- 12793915
TI  - Assessing sedation in the pediatric intensive care unit by using BIS and the
      COMFORT scale.
AB  - OBJECTIVE: To evaluate bispectral index technology in critically ill children and
      compare its performance to standard clinical assessment of sedation level.
      DESIGN: Prospective convenience sample. SETTING: Multidisciplinary 16-bed
      pediatric intensive care unit at a large, urban, university-affiliated children's
      hospital. PATIENTS: Thirty-one pediatric intensive care unit patients requiring
      mechanical ventilation and sedation. MEASUREMENTS AND MAIN RESULTS: Intubated,
      sedated, pediatric intensive care unit patients were evaluated for their level of
      sedation by using bispectral index (BIS) and the COMFORT scale twice daily for up
      to 5 days. The lowest and highest BIS measurements and their corresponding
      COMFORT scale measurements were selected from each subject. The mean BIS and
      COMFORT scale measurements were 62.4 +/- 2.6 and 18 +/- 0.6, respectively;
      however the individual measurements were only moderately correlated. The BIS
      values were categorized into very deep (<40), deep (41-60), moderate (61-80), and
      light (>80) levels of sedation. The corresponding COMFORT scale mean measurements
      in each category were 15.8 +/- 0.6, 16.2 +/- 0.6, 18.1 +/- 1.3, and 22.3 +/- 1.4
      (R(2) =.89). CONCLUSIONS: BIS measurements evaluated in clinically relevant
      ranges compare favorably with a standard assessment of the level of sedation.
      However, comparisons of BIS and COMFORT scale measurements at isolated moments
      during a prolonged pediatric intensive care unit course of sedation were less
      correlated. BIS may be best used to identify and prevent oversedation of patients
      in the pediatric intensive care unit.

PMID- 12793916
TI  - Use of vasopressin in refractory hypotension in children with vasodilatory shock:
      five cases and a review of the literature.
AB  - This article describes case studies of five children treated with vasopressin for
      refractory hypotension. In addition, physiology and pharmacology of vasopressin
      are reviewed in a comprehensive survey of the literature from 1966 until the
      present. In all five children, blood pressure increased immediately after
      vasopressin administration. The preliminary success of vasopressin for
      hypotension the setting of vasodilatory shock is promising. This limited use of
      vasopressin in the setting of refractory hypotension in these patients appears to
      be safe; the appropriate patient population and dose regimen are not yet
      determined.

PMID- 12793917
TI  - Detection of pepsin and glucose in tracheal secretions as indicators of
      aspiration in mechanically ventilated children.
AB  - OBJECTIVES: The detection of glucose in tracheal secretions has been used as an
      indicator of aspiration in mechanically ventilated, tube-fed children. Pepsin
      detection may be a more specific indicator. We determined the frequency of pepsin
      and glucose detection in tracheal secretions of mechanically ventilated children
      and studied the relationships between tracheal secretion pepsin and glucose and
      clinical evidence of gastroesophageal reflux. DESIGN: Prospective observational
      study. SETTING: University teaching hospital. PATIENTS: A convenience sample of
      mechanically ventilated children. INTERVENTIONS: Tracheal secretions were
      collected at the time of routine endotracheal tube suctioning. Tracheal aspirate
      glucose concentrations were assessed by using glucose oxidase reagent strips.
      Tracheal aspirate pepsin was detected by laboratory immunoassay. MEASUREMENTS AND
      MAIN RESULTS: One hundred tracheal aspirates were collected from 37 children.
      Pepsin (>or=1 microg/mL) was detected in nine aspirates, and glucose (>or=20
      mg/dL) was detected in 59 aspirates. Overall, five (13.5%) patients had at least
      one pepsin-positive aspirate, and 33 (89%) had at least one glucose-positive
      aspirate. Patients with at least one pepsin-positive aspirate were more likely to
      have clinical evidence of gastroesophageal reflux than patients with pepsin
      negative aspirates (5 of 5 vs. 9 of 32, p <.01, Fisher's exact test). Tracheal
      aspirate glucose positivity was unrelated to the administration of tube feedings
      and gastroesophageal reflux. No relationship between pepsin and glucose
      positivity was observed. CONCLUSIONS: Pepsin is detectable in tracheal secretions
      of mechanically ventilated children at risk for aspiration. Elevated glucose
      concentrations in tracheal secretions can occur by mechanisms other than
      aspiration of glucose-rich formula. Pepsin may be a more specific marker for
      aspiration than glucose.

PMID- 12793918
TI  - Soluble intercellular cell adhesion molecule-1 and L-selectin plasma
      concentrations and response to surfactant in preterm infants.
AB  - OBJECTIVE: To investigate whether plasma concentrations of soluble intercellular
      cell adhesion molecule (ICAM)-1 and L-selectin at 24 hrs of life are related to
      good or poor response to exogenous surfactant in preterm infants. DESIGN:
      Prospective study of markers of inflammation in circulating blood at 24 hrs of
      life. SETTING: Level III neonatal intensive care unit. PATIENTS: Twenty-nine
      preterm newborns suffering from severe respiratory distress syndrome (Fio(2) >
      0.4) without signs of infection or fetal acidosis, and 17 healthy preterm
      newborns of similar gestational age serving as controls. INTERVENTIONS: Infants
      with respiratory distress were treated with natural surfactant at 0.3-5 hrs of
      life. A response to surfactant, defined as a decrease of Fio(2) >50% within 6 hrs
      after surfactant, was seen in 21 infants. MEASUREMENTS AND MAIN RESULTS: Soluble
      ICAM-1 and L-selectin concentrations were determined in plasma samples taken at
      24 hrs of age. ICAM-1 was elevated (p <.001) in infants who responded poorly to
      surfactant (median, 392 ng/mL; range, 58.26-4884.24 ng/mL) compared with good
      responders (20.52 ng/mL, 2.32-138.58 ng/mL) or controls (21.91 ng/mL, 2.61-65.73
      ng/mL), without differences between controls and good responders. L-selectin was
      lower (p =.004) in surfactant-treated infants (4.45 nmol/L, 2.0-10.4 ng/mL) than
      in controls (6.0/2.35-10.25 nmol/L) without differences between surfactant good
      and poor responders. However, infants requiring supplemental oxygen at 36 wks of
      gestational age had reduced L-selectin at 24 hrs of age (3.2/2.0-3.45 vs.
      5.0/2.35-10.4 nmol/L, p =.004), whereas there was no difference in ICAM-1.
      CONCLUSIONS: In preterm infants with respiratory distress, a poor response to
      surfactant within 6 hrs of administration is associated with elevated circulating
      ICAM-1 concentrations at 24 hrs of age. Low plasma L-selectin at 24 hrs of age
      predicts prolonged requirement for supplemental oxygen.

PMID- 12793919
TI  - Airway oximetry improves monitoring of dopamine effects in pediatric cardiac
      patients.
AB  - OBJECTIVE: Simple, preferably noninvasive measurements of cardiac output are
      useful in pediatric patients receiving inotropic support. Oxygen saturation in
      pulmonary artery (Svo(2)) gives information about oxygen delivery and demand.
      Many inotropic drugs influence oxygen consumption. When effects on Svo(2) are
      studied, after a change in inotropic drug dosage, a change in oxygen consumption
      needs to be considered to accurately estimate the change in cardiac output. The
      aim of this investigation was to study whether information on inspired to end
      tidal oxygen concentration difference (Fi-eto(2)) in addition to Svo(2) would
      improve estimation of changes in cardiac output. DESIGN: Prospective
      observational study of Fi-eto(2), Svo(2), and oxygen saturation from central vein
      (Scvco(2)) for measurements of circulatory and metabolic effects of changes in
      dopamine dosage. SETTING: Intensive care unit in a children's hospital. PATIENTS:
      Twenty patients (age 4 days to 98 months) were studied after cardiac surgery.
      INTERVENTIONS: Dopamine was administered in doses of 5, 10, 0, and 5 microg x kg(
      1) x min(-1), 20 mins on each level. MEASUREMENTS AND MAIN RESULTS: Cardiac
      output, measured with thermodilution, oxygen saturation from systemic artery
      (Sao(2)), Svo(2), and Scvco(2) were measured at 15 mins on each dopamine dose.
      Oxygen consumption was calculated by using the Fick equation. Fi-eto(2) was
      measured continuously with a paramagnetic oxygen analyzer. Both cardiac output
      and oxygen consumption were affected by changes in dopamine dosage. Relative
      changes in cardiac output were poorly correlated to the change in 1/Sa-vo(2)
      (r(2) =.54). Using Fi-eto(2) improved correlation between changes in cardiac
      output and changes in Fi-eto(2)/Sa-vo(2) (r(2) =.72). When Svo(2) was replaced by
      Scvco(2), the correlation between changes in cardiac output and changes in Fi
      eto(2)/Sa-cvco(2) was only slightly altered (r(2) =.69). CONCLUSIONS: Dopamine
      affects oxygen consumption as well as cardiac output. The accuracy of Svo(2)
      based estimations of changes in cardiac output after dopamine is enhanced if
      changes in Fi-eto(2) are also considered. The more easily achievable Scvco(2)
      gave equivalent information as Svo(2).

PMID- 12793920
TI  - Effect of changes in inspired oxygen tension on indexes of oxygenation in
      ventilated neonates.
AB  - OBJECTIVE: Several indexes are used to quantify the severity of hypoxemia,
      including the arterial to alveolar oxygen ratio (a/APO(2)), the alveolar-arterial
      difference P(a-a)o(2), the ratio Pao(2)/Fio(2), and the oxygenation index (OI =
      mean airway pressure x Pao(2)/Fio(2)). This study was carried out to test how
      stable these indexes are when small changes in Fio(2) are made in ventilated
      neonates. DESIGN: Open prospective clinical study. SETTING: Level III neonatal
      intensive care unit of a teaching hospital. PATIENTS: Forty studies were
      performed in 31 clinically stable ventilated neonates (median birth weight, 1450
      g; median gestation, 30.6 wks), monitored by transcutaneous Pao(2)-oxygen
      saturation (Sao(2)). INTERVENTIONS: If hyper- or hypoxemia without derangements
      of Paco(2) or pH were detected in a blood sample taken from an indwelling
      arterial catheter, Fio(2) was changed (median change, 0.05; range, -0.3 to 0.25)
      and another arterial blood sample was obtained 26-83 mins (median, 42) after. The
      indexes were calculated in the two blood samples, and for each index the changes
      between baseline and the value after Fio(2) change were analyzed. MEASUREMENTS
      AND MAIN RESULTS: Median baseline P(a-a)o(2) was 211.7 torr, median a/APO(2) was
      0.24, median Pao(2)/Fio(2) was 161 torr, and median OI was 6.14. After the Fio(2)
      change, the coefficients of variation (sd/mean) were calculated, and they were
      27.5%, 23.8%, 24.5%, and 31.6% for P(a-a)o(2), a/APO(2), Pao(2)/Fio(2), and OI,
      respectively. Changes in the value of each index were correlated to changes in
      Fio(2), indicating a dependency on Fio(2). When data were analyzed as "high
      Fio(2)" (approximate Sao(2) 95%) vs. "low Fio(2)" (approximate Sao(2) 90%),
      differences were statistically significant for all indexes except for a/APO(2).
      CONCLUSIONS: All the indexes tested showed a dependency on the value of Fio(2):
      increasing Fio(2) spuriously made neonates appear less hypoxemic. The a/APO(2)
      appeared to perform better than other indexes in this study, with a lower
      variability and a lower oxygen dependency.

PMID- 12793921
TI  - Cerebrospinal fluid procalcitonin and severe traumatic brain injury in children.
AB  - OBJECTIVE: To determine the relationship between cerebrospinal fluid
      procalcitonin concentration and severe traumatic brain injury in children.
      DESIGN: Prospective, observational clinical study. SETTING: A multidisciplinary,
      tertiary-care pediatric intensive care unit. PATIENTS: Twenty-eight patients who
      required external ventricular drainage for management of severe traumatic brain
      injury (Glasgow Coma Scale score of <8) and 22 control patients for whom lumbar
      cerebrospinal fluid evaluation excluded possible meningitis. INTERVENTIONS:
      Standard intracranial pressure-directed neurointensive care, including
      intraventricular catheter placement and continuous cerebrospinal fluid drainage,
      was used to manage patients with severe traumatic brain injury. MEASUREMENTS AND
      MAIN RESULTS: Demographic data including age, mechanism of injury, time of
      injury, initial Glasgow Coma Scale score, and outcome were collected.
      Cerebrospinal fluid procalcitonin concentration was determined by
      immunoluminometric assay. Initial cerebrospinal fluid procalcitonin concentration
      (median [range]) in patients with severe traumatic brain injury was increased
      greater than three-fold vs. controls (0.41 ng/mL [0.15-2.14] vs. 0.12 ng/mL [0.00
      0.24], p <.001). Initial cerebrospinal fluid procalcitonin concentration among
      patients with abusive head trauma (0.31 ng/mL [0.29-0.50]) also was increased vs.
      controls (p <.05), although this increase was less robust than patients with
      accidental trauma (0.41 ng/mL [0.15-2.14], p <.001 vs. controls). Additional
      examination of key demographic and outcome variables with a generalized linear
      regression model was performed for patients with severe traumatic brain injury.
      Univariate analysis revealed that both time after injury (p <.01) and abusive
      head trauma as a mechanism of injury (p <.001) were associated with attenuation
      of the increased cerebrospinal fluid procalcitonin response after traumatic brain
      injury. CONCLUSION: Cerebrospinal fluid procalcitonin concentration is increased
      in children after traumatic brain injury. The attenuated increase in
      cerebrospinal fluid procalcitonin among victims of abusive head trauma warrants
      further study because it may reflect impairment of endogenous neuroprotective
      mechanisms or delay in seeking medical attention. The significance of these
      observations remains to be determined as future studies elucidate the physiologic
      and mechanistic properties of procalcitonin.

PMID- 12793922
TI  - Effect of increasing inspiratory time on respiratory mechanics in mechanically
      ventilated neonates.
AB  - OBJECTIVE: To investigate the effect of inspiratory time and inspiratory flow on
      the respiratory mechanics of intubated and ventilated neonates. DESIGN:
      Physiology study. SETTING: Tertiary university neonatal intensive care unit.
      PATIENTS: Neonates requiring mechanical ventilation with (group 1, n = 9) and
      without lung disease (group 2, n = 6). INTERVENTIONS: All infants were ventilated
      with a Servo 900C Siemens ventilator in the volume-controlled constant-flow mode.
      Flow and pressure were measured at the Y-piece, while different inspiratory times
      (25%, 33%, 50%, and 67% of the respiratory cycle) were applied randomly without
      changing tidal volume. MEASUREMENTS: The constant flow end-inspiratory airway
      occlusion technique allowed partitioning of the total respiratory system
      resistance (R(tot,rs)) into a standard intrinsic flow resistance (R(int,rs)) and
      a lung/thorax tissue viscoelastic component (DeltaR(rs)), and it allowed
      partitioning of the dynamic respiratory system elastance (E(dyn,rs)) into a
      static (E(st,rs)) and a lung/thorax tissue viscoelastic component (DeltaE(rs)). A
      two-compartment model of the respiratory system was applied to the experimental
      data. MAIN RESULTS: All respiratory mechanics components were significantly
      higher in group 1 compared with group 2. Both groups showed increasing R(int,rs)
      with increasing flow and increasing DeltaR(rs) with increasing inspiratory time.
      DeltaR(rs) represented 40% to 75% of R(tot,rs) whatever the group. E(dyn,rs) and
      E(st,rs) changed with inspiratory time in the very low (<0.4 secs) and the very
      long inspiratory time range (>1.0 secs). No change was found when clinically,
      commonly used inspiratory times were applied (0.4-1.0 secs). DeltaE(rs)
      represented 17% to 19% of E(dyn,rs). The relationship between DeltaR(rs) and
      increasing inspiratory time fitted the exponential two-compartment model (r =.99,
      p <.001). CONCLUSIONS: Total respiratory mechanics and its components in
      ventilated newborns with and without lung disease showed inspiratory time
      dependence. DeltaR(rs) increased with increasing inspiratory time as predicted by
      the two-compartment lung model, whereas standard R(int,rs) and E(dyn,rs)
      decreased.

PMID- 12793923
TI  - Albuterol delivery with conventional and synchronous ventilation in a neonatal
      lung model.
AB  - OBJECTIVE: To compare the percentage of nebulized albuterol delivered with
      conventional (intermittent mandatory ventilation) vs. synchronous (assist-control
      and assist-control with flow synchronization) ventilation in a neonatal lung
      model. DESIGN: Prospective in vitro laboratory study. SETTING: Research
      laboratory. SUBJECT: Neonatal lung model. INTERVENTIONS: The model simulated an
      intubated neonate with a spontaneous respiratory rate of 40, 60, or 80 breaths
      per minute and compliance and resistance values of bronchopulmonary dysplasia. A
      VIP Bird ventilator was used for all ventilator modes. Albuterol 2.5 mg was
      administered with a T Up-Draft II Neb-U-Mist nebulizer attached to a 12.75-cm (10
      mL) reservoir of circuit tubing. Albuterol was collected onto a filter (particle
      retention <or=0.3 microm) placed proximal to the test lung. After nebulization,
      the filter was rinsed with water, and albuterol concentrations were determined by
      high-performance liquid chromatography. Ten random trials for each mode were
      completed. MEASUREMENTS AND MAIN RESULTS: No significant differences in
      percentage albuterol delivered were found among the three modes or the three
      spontaneous respiratory rates (mean +/- sd): intermittent mandatory ventilation,
      0.11 +/- 0.04%; assist-control, 0.12 +/- 0.03%; assist-control with flow
      synchronization, 0.10 +/- 0.04%; 40 breaths per minute, 0.11 +/- 0.03%; 60
      breaths per minute, 0.11 +/- 0.04%; and 80 breaths per minute, 0.11 +/- 0.05% (p
      >.05, two-factor analysis of variance). CONCLUSIONS: The percentage of nebulized
      albuterol delivered to the end of the endotracheal tube in a mechanically
      ventilated neonatal model was not affected by mode of ventilation under the
      conditions studied. Further clinical studies are needed to determine whether lung
      deposition and distribution or clinical efficacy of albuterol is influenced by
      synchronous ventilation in this patient population.

PMID- 12793924
TI  - Transfusion-associated graft versus host disease.
AB  - OBJECTIVES: To review the epidemiology, pathophysiology, therapeutic and
      preventive strategies of transfusion associated graft versus host disease (TA
      GVHD) and relate the findings to the critically ill child. DESIGN: Review article
      of published medical literature related to TA-GVHD. DATA SOURCES: Medline,
      bibliography search, published national and institutional guidelines. STUDY
      SELECTION: Original publications including prospective studies, case reports,
      case series, laboratory studies, and animal work. DATA EXTRACTION: Data were
      extracted manually after we reviewed selected articles and assessed their
      contribution to knowledge of TA-GVHD. DATA SYNTHESIS: New and significant
      historic information from the selected publications relating to incidence,
      therapy, prevention, and complications of preventive therapy of TA-GVHD was
      incorporated. CONCLUSIONS: Pediatric critical care practitioners should be aware
      of this preventable but fatal complication of cellular blood product transfusion.
      High-risk categories include congenital and acquired immunodeficiency, younger
      age, transfusion of blood donated by family members, and transfusion with fresh
      whole blood. Children at risk for the development of TA-GVHD include neonates,
      infants, and children with congenital heart disease, not restricted to children
      with "classic" DiGeorge syndrome. At present, risk identification and targeted
      prevention are the only methods to manage TA-GVHD. Aside from minimizing cellular
      blood product exposure, blood product irradiation is the only established and
      widely available method to prevent TA-GVHD. Transfusion guidelines need to
      reflect a balance between the incidence of TA-GVHD and the costs of instituting
      irradiation to selected groups or as routine transfusion policy.

PMID- 12793925
TI  - Acute onset of Wegener's granulomatosis and diffuse alveolar hemorrhage treated
      successfully by extracorporeal membrane oxygenation.
AB  - Wegener's granulomatosis is a necrotizing granulomatous vasculitis involving the
      upper airway, lungs, and kidneys. Diffuse alveolar hemorrhage is a rare and life
      threatening presentation of Wegener's granulomatosis. We report on a previously
      healthy 13-yr-old boy who presented with fulminant pulmonary hemorrhage leading
      to acute respiratory distress syndrome and was found to have Wegener's
      granulomatosis. The diagnosis was based on clinical, radiologic, serologic, and
      histologic manifestations. The therapeutic challenges and the modalities of
      support to sustain life until clinical remission are presented.

PMID- 12793926
TI  - Neonatal hyperkalemic-hypocalcemic cardiac arrest associated with initiation of
      blood-primed continuous venovenous hemofiltration.
AB  - We report hyperkalemic-hypocalcemic cardiac arrest at the initiation of blood
      primed continuous venovenous hemofiltration in a 3-wk-old infant. Although
      hyperkalemia with massive transfusion has been reported and hemodynamic
      instability is not infrequent at the initiation of continuous venovenous
      hemofiltration in critically ill children, cardiac arrest in these circumstances
      is extremely rare at our institution and has not been reported in the literature.
      We report the case and discuss management strategies for blood-primed
      extracorporeal circuits.

PMID- 12793927
TI  - Noninvasive ventilation in the treatment of acute respiratory failure induced by
      all-trans retinoic acid (retinoic acid syndrome) in children with acute
      promyelocytic leukemia.
AB  - PURPOSE: To evaluate the feasibility of noninvasive ventilation through a nasal
      mask in the treatment of acute respiratory failure induced by all-trans retinoic
      acid. DESIGN: Observational, nonrandomized report of two cases. SETTING:
      Intensive care unit in a university hospital. PATIENTS: Two pediatric patients
      (an 11-yr-old male and a 12-yr-old female) affected by acute promyelocytic
      leukemia. INTERVENTIONS: Pressure support ventilation was delivered via a nasal
      mask by means of a bilevel positive pressure ventilator (Respironics,
      Murrysville, PA). MEASUREMENTS AND MAIN RESULTS: We evaluated the effects of the
      bilevel positive pressure ventilator on blood gas analysis, respiratory rate,
      hemodynamics, patient tolerance, complications, and outcome. Patients showed an
      improvement of blood gas analysis and respiratory rate after 3-6 hrs of
      noninvasive ventilation. The nasal mask was well tolerated by the two patients.
      No complications were observed. Patients were discharged from the intensive care
      unit in stable clinical conditions after 3-4 days. CONCLUSIONS: Noninvasive
      ventilation by a nasal mask can offer effective ventilatory support and improve
      gas exchange in the treatment of acute respiratory failure in pediatric
      hematologic patients. In addition, noninvasive ventilation may decrease the risk
      of life-threatening complications associated with endotracheal intubation and
      conventional mechanical ventilation in patients with hematologic malignancies.

PMID- 12793928
TI  - Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of
      arsenic insecticides in children.
AB  - OBJECTIVES: To describe the toxicokinetics and management of acute pediatric
      arsenic ingestion. DESIGN: Case report and literature review. SETTING: Tertiary
      pediatric intensive care unit, St. John's Children's Hospital, Springfield, IL.
      PATIENT: A 22-month-old boy ingested approximately twice the estimated lethal
      dose of arsenic trioxide (As(2)O(3)) ant bait. Only one household arsenical
      insecticide is available in the United States and is presumed to be shielded from
      human exposure. He survived without detectable sequelae. Initially, the patient
      developed signs of acute hemodynamic compromise with tachycardia, hypertension,
      gastrointestinal symptoms, and poor urine output. He became lethargic with muscle
      weakness and was somnolent but never developed encephalopathy, seizures, or late
      onset peripheral neuropathy. INTERVENTIONS: He was stabilized with fluid
      resuscitation, placed on a sodium bicarbonate intravenous drip, and treated with
      intramuscular dimercaprol (British anti-Lewisite), 5 mg/kg every 6 hrs for 3
      days. When the British anti-Lewisite and the sodium bicarbonate drip were
      discontinued, oral meso 2,3-dimercaptosuccinic acid (Succimer) was administered
      three times a day for 5 days and thereafter twice daily until the urine arsenic
      concentration decreased below 50 microg/L. MEASUREMENTS AND MAIN RESULTS:
      Continuous monitoring in the pediatric intensive care unit included continuous
      electrocardiogram, arterial blood pressure, urine output, vital signs, arterial
      blood gases, serum and urine arsenic concentrations, electrolytes,
      electromyography, and determination of arsenic toxicokinetics. The child's serum
      arsenic concentration was the highest ever reported with survival. CONCLUSIONS:
      Recovery from arsenic poisoning was attributable to the restoration and
      maintenance of adequate cardiac output and renal perfusion in early shock, which
      allowed depot intramuscular British anti-Lewisite to circulate and eliminate the
      poison. Although an intravenous antiarsenical chelating agent would be
      advantageous in treating shock from arsenic poisoning, none is currently
      available. We urge the immediate use of British anti-Lewisite therapy on patient
      presentation with suspected toxic arsenic ingestion.

PMID- 12793929
TI  - Protein S deficiency manifesting as spontaneous aortic thrombosis in a neonate.
AB  - PURPOSE: This article describes a neonate with protein S deficiency who presented
      with life-threatening thrombosis of the aorta. This is the first case report of a
      neonate with protein S deficiency presenting with aortic thrombosis. PATIENTS AND
      METHODS: A 9-day-old boy presented with a history of dark colored urine,
      vomiting, and apnea. The clinical examination was consistent with a coarctation
      of the aorta. An echocardiogram showed a normal arch of the aorta. An abdominal
      ultrasound done revealed an incompletely occluding thrombus in the aorta starting
      between the celiac axis and superior mesenteric artery to the aortic bifurcation.
      The patient was started on recombinant tissue plasminogen activator along with
      heparin and fresh frozen plasma. RESULTS: With tissue plasminogen activator, we
      were able to reestablish flow across the obstruction within a week. The patient
      had hypertension and renal failure that still requires dialysis. CONCLUSION:
      Protein S deficiency should be considered in a neonate with aortic thrombosis,
      and it can be treated successfully with a combination of high-dose tissue
      plasminogen activator and heparin followed by long-term heparin use.

PMID- 12793930
TI  - The impact of clinically significant upper gastrointestinal bleeding acquired in
      a pediatric intensive care unit.
AB  - OBJECTIVE: To determine the clinical and economic impact attributable to upper
      gastrointestinal bleeding (UGIB) acquired in a pediatric intensive care unit
      (PICU). DESIGN: Prospective case-control-within-cohort study. SETTING: PICU at a
      university hospital. PATIENTS: All consecutive patients over a 1-yr period.
      METHODS: All UGIB (hematemesis or blood in gastric tube) were reported. A UGIB
      was qualified as clinically significant (CS-UGIB) if a panel of reviewers
      assessed that a complication (decreased hemoglobin concentration, transfusion,
      multiple organ dysfunction syndrome, surgery, or death) was attributed to it. A
      UGIB was qualified as clinically nonsignificant (NS-UGIB) if none of these
      complications was attributed to it. The O-UGIB group comprised patients without
      UGIB. Pairing between the three groups was done according to these criteria:
      death or survival, Pediatric Risk of Mortality Score on admission, respiratory
      failure, coagulopathy, and age. Data considered for the impact analysis was
      prospectively monitored during the stay in PICU. Costs were estimated in Canadian
      dollars (1999) as follows: costs of stay + medical staff + ventilation + red
      blood cell transfusions. RESULTS: The cohort included 1006 admissions. Sixteen
      cases of CS-UGIB were paired to 13 cases of NS-UGIB and 32 cases of O-UGIB.
      Compared with the O-UGIB group and the NS-UGIB group, the CS-UGIB group showed a
      significantly (p < 0.05) higher rate of red blood cell transfusions, duration of
      ventilation, length of stay in PICU, and a lower hemoglobin level. There was no
      difference between the NS-UGIB group and the O-UGIB group. The cost analysis
      demonstrated a significant difference (p < 0.05) between the CS-UGIB group
      (20,062.67 Can dollars/patient per stay) and the other groups (NS-UGIB, 6104.77
      Can dollars/patient per stay; O-UGIB, 5457.25 Can dollars/patient per stay).
      CONCLUSION: This study demonstrates a significant clinical and economic impact of
      CS-UGIB in PICU, although no impact was detected for NS-UGIB. Further studies on
      the benefit of UGIB prophylaxis for critically ill children with risk factors for
      CS-UGIB are needed.

PMID- 12793931
TI  - The impact of molecular biology on the practice of pediatric critical care
      medicine.
AB  - Molecular biology is increasingly affecting all areas of clinical medicine,
      including pediatric critical care medicine. Recent advances in genomics will
      allow for a more in-depth understanding of disease processes that are relevant to
      the pediatric intensivist, such as sepsis, the acute respiratory distress
      syndrome, and multiple organ dysfunction syndrome. In turn, understanding
      critical illness at the genomic level may allow for more effective stratification
      of patient subclasses and targeted, patient-specific therapy. The related fields
      of pharmacogenomics and pharmacogenetics hold the promise of improved drug
      development and the tailoring of drug therapy based on the individual's drug
      metabolism profile. Therapeutic strategies aimed at modulating host inflammatory
      responses remain viable but will need to take into account the inherent
      redundancy of the host inflammatory response and the heterogenous responses
      between individual patients. Thus, "immuno-phenotyping" of critically ill
      patients will allow for more rational immune-modulating therapies, either in the
      form of inhibiting or enhancing specific immune/inflammatory responses. The host
      also contains powerful, broad cytoprotective mechanisms that could potentially be
      harnessed as a strategy for organ and tissue protection in many forms of critical
      illness. Finally, prospects for gene therapy, although quite challenging at
      present, may be applicable to the intensive care unit in the near future. With
      these rapid advancements in molecular biology, it is imperative that all
      pediatric critical care practitioners become, at least, familiar with the field
      and its related technology. Hopefully, clinician-scientists involved in pediatric
      critical care will also shape the direction of these future prospects.

PMID- 12793932
TI  - Compliance with hand hygiene practice in pediatric intensive care.
AB  - OBJECTIVE: To determine the frequency and predictors of compliance with hand
      hygiene (HH) practice in pediatric intensive care. DESIGN: Observational,
      prospective cohort study performed from February to April 2000. SETTING: Three
      intensive care units at a tertiary care children's hospital. PARTICIPANTS:
      Nurses, physicians, respiratory therapists, and other healthcare workers.
      METHODS: During 156 30-min daytime observation periods, an unidentified observer
      monitored 2811 opportunities for HH during patient care and recorded HH
      compliance. MEASUREMENTS AND MAIN RESULTS: Average HH compliance was 34%
      (946/2811). It was higher (p < 0.001) among respiratory therapists (68%; 171/251)
      than physicians (37%; 157/426) or nurses (29%; 587/2031). Contact with body fluid
      secretions was associated with the highest compliance (77%; 46/60), and contact
      with wounds (71%; 10/14) or indwelling devices (66%; 110/167) were associated
      with somewhat lesser compliance. The following were important predictors of
      compliance (all p < 0.01): being a respiratory therapist (odds ratio [OR], 5.1);
      working in the neonatal intensive care unit (OR, 1.6); and contact with invasive
      devices (OR, 2.5), wounds (OR, 6.9), or body fluids (OR, 11.5). Compliance was
      lowest after interrupted patient-care activities (9%; OR, 0.15). Surprisingly,
      decreased patient-to-nurse ratio (mean, 1.3 +/- 0.3) or opportunities per hr of
      care (mean, 37 +/- 7) were not independent predictors of compliance. CONCLUSIONS:
      Average HH compliance was low, but it increased during high-risk patient-care
      activities. Intensified efforts are necessary to increase caretakers' compliance
      and the awareness of the risk of bacterial contamination after interrupted
      patient-care activities.

PMID- 12793933
TI  - Stability of dopamine and epinephrine solutions up to 84 hours.
AB  - OBJECTIVES: The current practice of preparing fresh dopamine and epinephrine
      solutions every 24 hrs may lead to hemodynamic instability caused by the
      interruption of infusions with each change. We determined the stability of these
      catecholamines over an 84-hr period and whether stability was enhanced by
      dextrose-containing solutions. SETTING: Tertiary care teaching hospital. DESIGN:
      The stability of dopamine and epinephrine, each at three commonly used
      concentrations, was studied in three vehicles (10 gm/dl dextrose in water [D10W],
      5 gm/dl dextrose in water [D5W], and 0.9% NaCl in water [NS]). To mimic clinical
      conditions, solutions were placed on syringe pumps infusing continuously into a
      closed system at ambient temperature for 84 hrs. MEASUREMENTS: Concentrations of
      dopamine in mg/ml and epinephrine in microg/ml were measured by high-performance
      liquid chromatography at 0, 24, 36, 48, 72, and 84 hrs. RESULTS: Dopamine and
      epinephrine concentrations did not change over the 84-hr period regardless of the
      vehicles in which the drugs were prepared. CONCLUSIONS: Clinically relevant
      concentrations of dopamine and epinephrine remain stable in dextrose- and saline
      containing solutions for >or=84 hrs. These data suggest that solutions of these
      catecholamines may safely be used in clinical practice beyond the currently
      recommended 24 hrs.

PMID- 12793934
TI  - Respiratory syncytial virus infections in the pediatric intensive care unit:
      clinical characteristics and risk factors for adverse outcomes.
AB  - OBJECTIVES: To describe the clinical characteristics of infants admitted to a
      pediatric intensive care unit (PICU) with respiratory syncytial virus (RSV)
      infection, including the prevalence of indications for RSV passive antibody
      prophylaxis (as currently recommended by the American Academy of Pediatrics), and
      to identify risk factors that predict adverse outcomes among this population.
      DESIGN: Retrospective medical record review. SETTING: Tertiary care PICU.
      PATIENTS: Children <2 yrs of age admitted to PICU for the management of RSV
      disease during the 1994-95, 1995-96, and 1996-97 RSV seasons. MEASUREMENTS AND
      MAIN RESULTS: The medical records of 89 infants were reviewed. Of these, 55% were
      born before 36-wks gestation, 14% had chronic lung disease that required medical
      therapy within the previous 6 months, and 30% met at least one indication for RSV
      passive antibody prophylaxis. Seven infants had congenital heart disease, five
      had upper airway abnormalities, and six had various noncardiac congenital
      malformations. Logistic regression was used to determine which characteristics
      were associated with prolonged durations (>75th percentile) of mechanical
      ventilation, PICU stay, and hospital stay. Prolonged mechanical ventilation was
      associated with congenital heart disease (p = 0.014), chronic lung disease (p =
      0.007), and noncardiac congenital malformations (p = 0.022). Only congenital
      heart disease was associated with prolonged PICU stay (p = 0.004) or prolonged
      hospital stay (p = 0.006). All of the infants with airway abnormalities had
      prolonged ventilator days, PICU days, and hospital days. Currently recommended
      indications for RSV passive antibody prophylaxis were not predictive of prolonged
      ventilation, PICU stay, or hospital stay. CONCLUSIONS: A minority of infants
      admitted to our PICU for severe RSV disease meet currently recommended
      indications for RSV passive antibody prophylaxis. Risk factors that predict
      prolonged durations of ventilation, PICU stay, or hospital stay among this
      population include congenital heart disease, chronic lung disease, upper airway
      abnormalities, and noncardiac congenital malformations.

PMID- 12793935
TI  - Parental coping and bereavement outcome after the death of a child in the
      pediatric intensive care unit.
AB  - OBJECTIVE: Parental grief after the death of a child may be influenced by the
      chronicity of the child's illness, the quality of care provided, and the parents'
      ability to cope. Our objective is to identify aspects of pediatric intensive care
      and parental coping that have a favorable effect on parental bereavement outcome.
      DESIGN: Follow-up survey. SETTING: University teaching hospital. PARTICIPANTS:
      Fifty-seven parents who experienced the death of their child in the pediatric
      intensive care unit between January 1, 1995, and June 30, 1998. INTERVENTIONS:
      Parents completed two standardized questionnaires, the Coping Resources Inventory
      and the Texas Revised Inventory of Grief. The Coping Resources Inventory
      quantifies five coping resources: cognitive, social, emotional, spiritual, and
      physical. The Texas Revised Inventory of Grief is a two-part questionnaire that
      quantifies the intensity of grief at two time points: (1) near the time of death,
      and (2) in the present. Parents had previously participated in an interview with
      the investigators that included questions regarding the emotional attitudes of
      the pediatric intensive care unit staff and the adequacy of information provided
      during their child's critical illness. MAIN OUTCOME MEASURES: Texas Revised
      Inventory of Grief scores were used as measures of early and long-term grief.
      RESULTS: Parents' whose child died acutely had greater intensity of early and
      long-term grief than those whose child died of chronic illness (p < 0.05, Mann
      Whitney U test). Parents' physical coping resources and the emotional attitudes
      of pediatric intensive care unit staff predicted the intensity of early grief
      (R(2) =.27, multiple regression). Parents' cognitive coping resources, the
      emotional attitudes of staff, and the adequacy of information provided to parents
      predicted the intensity of long-term grief (R(2) =.42). CONCLUSIONS: Parents'
      physical well-being enables more effective handling of early grief. Parents'
      understanding of their own self-worth and their child's illness determine long
      term adaptation to loss. A caring emotional attitude displayed by pediatric
      intensive care unit staff has beneficial short-term and long-term effects on
      parental bereavement.

PMID- 12793936
TI  - Efficacy of an enteral 10-day methadone wean to prevent opioid withdrawal in
      fentanyl-tolerant pediatric intensive care unit patients.
AB  - OBJECTIVE: To demonstrate the efficacy of a 10-day, single daily dose, enteral
      methadone weaning protocol for the prevention of opioid withdrawal symptoms in
      pediatric patients after prolonged fentanyl exposure. DESIGN: Prospective,
      observational study. SETTING: Twenty-four-bed medical-surgical intensive care
      unit within a 222-bed pediatric teaching hospital. PATIENTS: Twenty-nine
      children, aged 1 day to 19.8 yrs, who received methadone to prevent opioid
      withdrawal after prolonged continuous fentanyl infusion exposure. INTERVENTIONS:
      Institution of a standardized methadone weaning protocol. MEASUREMENTS AND MAIN
      RESULTS: All 29 patients had received a continuous fentanyl infusion; duration of
      exposure was 14.5 +/- 9.2 days, cumulative fentanyl dose was 1.93 +/- 1.53 mg/kg,
      and peak fentanyl infusion was 9.6 +/- 4.3 microg/kg per hr. Twenty-five (86%) of
      29 patients successfully completed the methadone wean in 10 days. Withdrawal
      complications that required a weaning delay were seen in three patients, and one
      patient expired before completion. Sixteen patients were discharged to complete
      their weaning schedule at home without incident. CONCLUSIONS: Opioid withdrawal
      symptoms in pediatric intensive care unit patients after prolonged fentanyl
      exposure can be avoided by using an enteral, 10-day, single daily dose methadone
      weaning protocol.

PMID- 12793937
TI  - The cardiovascular effects of partial liquid ventilation in newborn lambs after
      experimental meconium aspiration.
AB  - OBJECTIVE: To study the effects of partial liquid ventilation with
      perfluorocarbon on cardiovascular function, pulmonary gas exchange, and lung
      mechanics in term newborn lambs with pulmonary hypertension induced by tracheal
      instillation of human meconium. DESIGN: Prospective, randomized study. SETTING:
      Research Unit at a university-affiliated hospital. SUBJECTS: Twelve term newborn
      lambs (<6 days old). INTERVENTIONS: Lambs were studied in two groups (n = 6):
      meconium aspiration (3-5 ml/kg 20% meconium solution) managed on pressure-limited
      conventional mechanical ventilation with or without partial liquid ventilation
      with perfluorocarbon. MEASUREMENTS AND MAIN RESULTS: Heart rate, systemic and
      pulmonary arterial pressures, arterial pH and blood gases, cardiac output, and
      pulmonary mechanics were measured. Partial liquid ventilation in term newborn
      lambs with experimental meconium aspiration did not alter cardiovascular profile:
      heart rate, systemic arterial pressure, and cardiac output maintained initial
      values throughout the experiment. There was a significant improvement in gas
      exchange (oxygenation increased from values of <100 torr to 338 torr, and
      ventilation reached normal values in 15 mins). Dynamic compliance increased in 30
      mins, reaching basal values (1.1 +/- 0.3 ml/cm H(2)O per kg). Despite the good
      response (blood gases and cardiovascular profile) to partial liquid ventilation
      in meconium aspiration syndrome, pulmonary hypertension did not decrease.
      CONCLUSIONS: Partial liquid ventilation with perfluorocarbon could be a good
      noninvasive alternative technique that improves gas exchange and pulmonary
      mechanics in meconium aspiration syndrome without impairing cardiovascular
      function.

PMID- 12793938
TI  - Cerebral hypoxemia-ischemia and reoxygenation with 21% or 100% oxygen in newborn
      piglets: effects on extracellular levels of excitatory amino acids and
      microcirculation.
AB  - OBJECTIVE: To determine whether reoxygenation with 21% oxygen is preferable to
      100% oxygen in normalizing extracellular levels of excitatory amino acids in the
      brains of hypoxic-ischemic newborn piglets and to compare this model of combined
      hypoxemia-ischemia to a previously used model of global hypoxemia. DESIGN:
      Prospective, randomized animal study. SETTING: Surgical research laboratory.
      SUBJECTS: Twenty-four anesthetized piglets, 1-3 days old. INTERVENTIONS:
      Hypoxemia-ischemia was achieved by normoventilation with 8% oxygen and temporary
      occlusion of the common carotid arteries. After 20 mins, reoxygenation
      reperfusion was started with 21% oxygen (HI 21% group, n = 12) or 100% oxygen (HI
      100% group, n = 12) for 30 mins followed by 21% oxygen. All piglets were observed
      for 2 hrs. MEASUREMENTS AND MAIN RESULTS: We measured extracellular
      concentrations of amino acids in striatum and hypoxanthine in cerebral cortex
      (microdialysis), microcirculation in cerebral cortex (laser Doppler), plasma
      hypoxanthine, and mean arterial pressure. During the 2-hr reoxygenation
      reperfusion period, levels of amino acids were significantly higher in the HI 21%
      group compared with the HI 100% group (glutamate, p = 0.02; aspartate, p = 0.03).
      Mean arterial pressure was significantly lower in the HI 21% group (p = 0.04).
      Microcirculation decreased to <10% of baseline during hypoxemia-ischemia and
      normalized during reoxygenation-reperfusion in the HI 100% group, but it remained
      at a significantly lower level in the HI 21% group (p = 0.03). CONCLUSIONS:
      Significantly higher levels of excitatory amino acids in striatum, significantly
      lower mean arterial pressure, and a significantly greater degree of hypoperfusion
      in cerebral cortex were found after reoxygenation with 21% oxygen compared with
      100% oxygen in normocapnic, hypoxemic-ischemic newborn piglets. This suggests a
      less favorable outcome in the group receiving room air.

PMID- 12793939
TI  - The use of a mobile computed tomography scanner in the pediatric intensive care
      unit to evaluate airway stenting and lung volumes with varying levels of positive
      end-expiratory pressure.
AB  - OBJECTIVE: Presentation of a case report describing the use of a mobile computed
      tomography (CT) scanner in the pediatric intensive care unit (PICU) to
      radiographically evaluate tracheobronchial stenting and lung volumes while using
      different levels of positive end-expiratory pressure (PEEP) and positioning in a
      critically ill infant. DESIGN: Case report of a single patient. SETTING:
      Pediatric intensive care unit in a University Hospital. PATIENT: A 6-month-old
      premature infant with bronchopulmonary dysplasia, tracheobronchomalacia, and
      progressive respiratory failure. INTERVENTIONS: CT scans of the chest were
      performed by using a mobile CT scanner in the PICU. Serial CT scans were
      performed at PEEP levels of 5, 10, 15, and 20 cm H(2)O in both the supine and
      prone position. Scheduled medical care and standard monitoring were continued
      during the course of the CT scans. MEASUREMENTS AND MAIN RESULTS: Identical
      anatomic levels demonstrating the trachea, bronchi, and lung parenchyma were
      compared while different levels of PEEP and supine or prone positioning were
      used. From these comparisons, the level of PEEP in which lung volumes were
      optimized was radiographically determined. No significant changes in large airway
      caliber were observed. There was no difference noted between prone and supine
      positioning. CT scans were completed with minimal disruption to the patient's
      care. CONCLUSIONS: Mobile CT scanners can be used in the PICU for the diagnostic
      evaluation of critically ill children. This option allows for the continuation of
      medical therapies and monitoring in the intensive care setting while avoiding the
      potential complications of transporting a critically ill child to the radiology
      department. The use of mobile CT scanners may disrupt PICU routine and is more
      expensive than use of fixed CT scanners. Mobile CT scanners may be useful in
      radiographically determining the optimal level of PEEP in infants with
      tracheobronchomalacia and bronchopulmonary dysplasia.

PMID- 12793940
TI  - Microvascular thrombosis in pediatric multiple organ failure: Is it a therapeutic
      target?
AB  - PURPOSE: To discuss the current rationale for the use of specific and nonspecific
      therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric
      multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations
      and proceedings of recent critical care meeting presentations were reviewed.
      RESULTS: Critical care clinicians have reported using antithrombin III
      concentrate, protein C concentrate, activated protein C, prostacyclin and its
      analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion,
      plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen
      activator, urokinase, and streptokinase with perceived therapeutic benefits in
      patients with thrombocytopenia-associated multiple organ failure, including those
      with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated
      intravascular coagulation syndrome, and secondary thrombotic microangiopathy
      syndrome without prolonged prothrombin time/activated partial thromboplastin
      time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has
      developed that thrombotic microangiopathy is a therapeutic target in children
      with thrombocytopenia-associated multiple organ failure syndromes. Studies are
      warranted to delineate efficacious use of specific and nonspecific therapies to
      prevent and reverse thrombotic microangiopathy in these patients.

PMID- 12793941
TI  - Mechanical ventilatory support in infants with respiratory syncytial virus
      infection.
AB  - OBJECTIVE: To present a review of current knowledge of the use of mechanical
      ventilatory support in the management of infants with respiratory failure
      secondary to infection with respiratory syncytial virus (RSV). DATA SOURCES:
      MEDLINE and manual search for case reports and clinical trials that address
      management strategies for respiratory support of infants with RSV infection. Data
      Extraction and Synthesis: Critical appraisal of reported epidemiologic and
      clinical data regarding risk factors, pathophysiology, and efficacy of
      respiratory therapy. There is an increasing number of hospital admissions for RSV
      infection with a variable proportion of infants who need mechanical ventilatory
      support. The mortality rate is estimated to be <1% in infants without preexisting
      respiratory or cardiac disorders vs. <5% in those with preexisting respiratory or
      cardiac disorders. Optimal ventilator settings need to be refined according to
      the dominant obstructive or restrictive pattern with the aim to avoid
      barovolutrauma. The role of noninvasive ventilation and additional therapies
      (heliox, beta(2) agonists, surfactant) is not conclusively established. The
      indications for high-frequency oscillatory ventilation with the possible
      adjunction of inhaled nitric oxide deserve further study. Extracorporeal membrane
      oxygenation plays a minor role in severe cases that are refractory to
      conventional treatment. CONCLUSIONS: Conventional ventilation strategies are
      usually adequate for treating infants with severe RSV infection. Particular
      attention must be paid to the dominant pathophysiologic mechanism in a given
      condition. Prospective trials are needed to validate alternative therapeutic
      options and to improve the outcome of the rare but most severe cases that are
      difficult to control.

PMID- 12793942
TI  - Prospective documentation of sedative, analgesic, and neuromuscular blocking
      agent use in infants and children in the intensive care unit: A multicenter
      perspective.
AB  - OBJECTIVE: To describe the use of neuromuscular blocking agents (NMBA) in
      critically ill children. DESIGN: Prospective cohort study. SETTING: Two pediatric
      intensive care units (ICUs). PATIENTS: All children who received NMBA in the ICUs
      during the study year. INTERVENTIONS: None Measurements: Data on use of NMBA
      agents and concurrent use of narcotic and sedative agents were collected.
      Demographic and outcome information was also obtained. MAIN RESULTS: NMBAs were
      used for either short-term (<6 hrs) or long-term neuromuscular blockade in 6%-9%
      of patient ICU days and for long-term blockade in 14%-16% of ventilatory support
      days. The overall mortality rate among ICU patients who received NMBA was 18%.
      Choice of agent varied between ICUs; however, succinyl choline was used in only
      1% of cases for short-term neuromuscular blockade. The most frequent indication
      for long-term NMBA use was facilitation of mechanical ventilatory support (49%).
      Among these children, 46% received high frequency oscillatory ventilation. Long
      term neuromuscular blockade was most frequently monitored by clinical examination
      rather than peripheral nerve stimulation. Paralysis for >6 hrs after
      discontinuation of NMBA was significantly more common when the agent was
      administered as an infusion instead of as bolus doses. Myopathy after long-term
      use of NMBA was seen in only 1 patient (0.4%). Doses (mg/kg) of NMBA did not
      significantly vary by patient age, but they did increase over time. CONCLUSIONS:
      Use of NMBA is more common in critically ill children than in reported studies of
      critically ill adults. Use of NMBA in critically ill children is associated with
      high severity of illness and mortality rates. Choice of NMBA and method of
      administration varies among providers. Concurrent use of narcotic and sedative
      agents with NMBA is frequent, but medication choice also varies among medical
      providers.

PMID- 12793943
TI  - The semi-elective use of the pulmonary artery flotation catheter in children with
      progressive pulmonary hypertension or left ventricular dysfunction.
AB  - OBJECTIVE: To describe the experience with the semi-elective use of the pulmonary
      artery flotation catheter in pediatric patients with progressive pulmonary
      hypertension or left ventricular dysfunction. DESIGN: Prospective study. SETTING:
      Pediatric intensive care unit in a tertiary care center. PATIENTS: Seven
      consecutive children with pulmonary hypertension and ten children with left
      ventricular dysfunction. INTERVENTIONS: Drug-response studies were performed
      using a pulmonary artery flotation catheter. Cardiac index, systemic and
      pulmonary blood pressure, and occlusion pressure were measured during incremental
      doses of calcium channel blocker (diltiazem) that were administered to children
      with pulmonary hypertension and during incremental doses of nitroglycerine and
      angiotensin-converting enzyme-inhibitor (captopril) that were administered to
      patients with left ventricular dysfunction. MAIN RESULTS: Four patients (60%)
      with pulmonary hypertension were identified as responders to calcium channel
      blockers, resulting in maintenance therapy with high-dose diltiazem in three of
      them. Nine patients (90%) with left ventricular dysfunction showed a >15%
      increase in cardiac index with vasodilator therapy. Eleven patients (65%)
      developed fever during the procedure. Nine patients (53%) had a high probability
      of bacterial infection. Seven patients (40%) died within 3.5 months after the
      procedure. Fever, infection, and mortality appeared to occur more frequently in
      patients in New York Heart Association classes III and IV. CONCLUSIONS: The use
      of a pulmonary artery flotation catheter enables us to optimize medical treatment
      strategies in the individual child with progressive pulmonary hypertension or
      left ventricular dysfunction. Children with left ventricular dysfunction in poor
      clinical condition showed a high mortality rate post or propter the procedure. In
      our opinion, drug-response studies using pulmonary artery flotation catheters in
      patients with left ventricular dysfunction should be performed in a relatively
      early stage of the disease.

PMID- 12793944
TI  - Early postoperative arrhythmias after open-heart procedures in children with
      congenital heart disease.
AB  - OBJECTIVE: Evaluation of occurrence, clinical course, necessity of treatment, and
      outcome of early postoperative cardiac arrhythmias after open-heart surgery.
      DESIGN: Prospective study. SETTING: Tertiary pediatric intensive care and
      pediatric cardiology unit. PATIENTS: All consecutive pediatric patients
      undergoing cardiac surgery on cardiopulmonary bypass were studied for the
      occurrence of cardiac arrhythmias during the whole perioperative hospital stay.
      Measurements: All patients had continuous electrocardiographic monitoring (with
      memory function) during the whole intensive care stay. A 24-hr Holter recording
      was done thereafter in patients with arrhythmias. RESULTS: Of 310 patients
      studied, 83 (27%) had postoperative arrhythmias. The occurrence rate was not
      different whether surgical access was by atriotomy or ventriculotomy (26% vs.
      28%, respectively). Infants (39%) and cyanotic patients (36%) had a higher
      occurrence rate of arrhythmias (p <.05). Arrhythmias were more common after
      prolonged cardiopulmonary bypass time and with higher postoperative maximum
      troponin serum levels. In addition, patients with hemodynamically significant
      residual findings after correction had an increased occurrence rate of
      arrhythmias (18 of 43; 42%; p <.01). Of the 83 children with arrhythmias, 53
      (64%) required specific antiarrhythmic treatment. The use of antiarrhythmic drugs
      was required in only 7 of these patients. Only one patient (1.2% of patients with
      arrhythmias) died from arrhythmia. No major complications resulting from
      arrhythmias occurred during the postoperative clinical course in the other
      patients. CONCLUSIONS: Although they occur frequently, postoperative arrhythmias
      after open-heart procedures in children are associated with low morbidity and
      mortality.

PMID- 12793945
TI  - Young age is not a predictor of mortality in burns.
AB  - OBJECTIVE: Conventional wisdom and recently published reports suggest that
      children <48 months of age have a higher mortality rate after burns than older
      children and adolescents with similar injuries and that young age is a predictor
      of mortality. This study was done to validate or refute this impression. DESIGN:
      Retrospective review. SETTING: Regional pediatric burn center. PATIENTS: All
      children (n = 1223) managed over a recent 8-yr interval (1991-1998) for acute
      thermal burns. INTERVENTIONS: The survival rate of children <48 months of age was
      compared with the survival rate of children >/=48 months of age. MEASUREMENTS AND
      MAIN RESULTS: Of the 1112 children with burns covering <30% of the body surface,
      721 (65%) were <48 months of age. After exclusion of one child who was brain dead
      and became a solid organ donor, there were no deaths in this burn size group.
      There were 111 children admitted with burns covering >/=30% of the body surface:
      47 (42%) with an average age of 2.0 yrs (range, 4 wks to 3 yrs and 11 months)
      were <48 months of age, and 64 (58%) with an average age of 10.9 yrs (range, 4
      yrs to 17 yrs) were >/=48 months of age. There were no clinically important
      differences between the two groups in burn size (51.9% +/- 18.1% [range, 30%-90%]
      vs. 56.9% +/- 19.4% [range, 30%-97%]; p =.18) or need for mechanical ventilatory
      support (30/47 [63.8%] vs. 44/64 [68.8%]; p =.59). The mortality rate in the
      young group was 0% (0/47) and 10.9% (7/64) in the older group (p =.04). All
      children who died had large burns (average burn size, 82.9% +/- 11.5%) with
      concurrent inhalation injury. CONCLUSION: Young age is not a predictor of
      mortality in burns.

PMID- 12793946
TI  - Early severe neutropenia and thrombocytopenia identifies the highest risk cases
      of severe meningococcal disease.
AB  - OBJECTIVE: To determine the performance of established predictors of mortality in
      pediatric acute meningococcal disease (MD) in a contemporary population and to
      develop a simple predictive score that will not vary with observer. DESIGN:
      Prospective study for development set and mixed retrospective and prospective
      study for validation set. Setting and PATIENTS: A total of 227 patients with
      clinical meningococcal disease who were referred to three multidisciplinary
      pediatric intensive care units from 1993 to 1999. Early deaths before transfer to
      pediatric intensive care unit and deaths from cerebral herniation were included
      in the analysis. MEASUREMENTS AND MAIN RESULTS: The product of platelet and
      neutrophil counts at presentation (PN product) predicts mortality from
      meningococcal disease better than either count alone and at least as well as
      established severity scores. The Glasgow Meningococcal Septicaemia Prognostic
      Score and Malley scores performed poorly in these populations. The positive
      predictive value (PPV) for a Glasgow meningococcal septicemia prognostic score of
      >/=8/15 was 17.5% (16 of 91; 95% CI = 9%-25%), significantly lower than published
      estimates of 30%-74%, (p <.01). The PPV for death (or amputation) with a Malley
      score of 3/3 was 50% (12 of 24; 29%-71%), significantly lower than the published
      value of 100% (p <.001). The PN product appears to be a useful predictor. For a
      PN product of <40, PPV = 82% (9 of 11), specificity = 99% (195 of 197), and
      sensitivity = 73% (23 of 30). The performance of this score was greatest in
      younger children <5 yrs of age in whom clinical cerebral herniation was not seen
      as a cause of death (0 of 21 deaths at <5 yrs of age; 4 of 9 deaths at >/=5 yrs
      of age). CONCLUSION: Established scores significantly overestimate the occurrence
      of adverse outcomes in meningococcal disease. This may reflect improved
      resuscitation and outcome or variability in the application of these scores. The
      PN product achieves similar prediction to the scores currently in use and is
      independent of the observer. Factors that reflect the extent of the inflammatory
      response rather than the care before presentation are becoming increasingly
      important.

PMID- 12793947
TI  - Omeprazole pharmacodynamics and gastric acid suppression in critically ill
      pediatric transplant patients.
AB  - OBJECTIVE: To characterize the pharmacodynamics and pharmacokinetics of
      omeprazole suspension in critically ill pediatric liver/intestinal transplant
      patients. DESIGN: Open-label pharmacodynamic and pharmacokinetic study. SETTING:
      Pediatric intensive care unit of an academic medical center. PATIENTS: Eleven
      pediatric liver and/or intestinal transplant patients. INTERVENTIONS:
      Extemporaneously prepared 0.5 mg/kg omeprazole suspension every 12 hrs via
      nasogastric tube before sequential measurements of omeprazole serum concentration
      and gastric pH monitoring. Gastric pH was monitored continuously for 48 hrs and
      plasma omeprazole concentrations were determined upon first and multiple dosing.
      MEASUREMENTS AND MAIN RESULTS: Mean onset of action of omeprazole in a sodium
      bicarbonate vehicle was 62 +/- 82 mins (range, 2-226 mins). Subjects <4 yrs of
      age exhibited a more variable onset of omeprazole action (range, 3-226 mins) when
      compared with older subjects (onset of action, 2-40 min). Omeprazole maximum
      concentration and area under the concentration-time curve for the dosage interval
      were significantly greater upon multiple dosing when compared with the first
      dose. Mean baseline gastric pH in this study population was 1.0 +/- 0.8. Gastric
      pH remained >4.0 for 78.8% +/- 18.9% of the first dosage interval and 97.8% +/-
      5.4% of multiple dosage intervals regardless of age when administered twice daily
      as a suspension. CONCLUSION: These results support the use of omeprazole
      administered twice daily as a suspension to maintain gastric pH of >4.0 and to
      achieve maximal pharmacodynamic effect in pediatric liver and/or intestinal
      transplant patients.

PMID- 12793948
TI  - Survival and renal function in pediatric patients following extracorporeal life
      support with hemofiltration.
AB  - OBJECTIVE: To determine variables associated with survival in pediatric patients
      treated with hemofiltration while receiving extracorporeal life support and to
      determine the probability for recovery of renal function among survivors. DESIGN:
      Retrospective database analysis. SETTING: University of Michigan pediatric
      nephrology database. PATIENTS: All pediatric patients treated with continuous
      hemofiltration while on extracorporeal life support at the University of Michigan
      between January 1990 and May 1999. A pediatric patient was defined as any child
      between birth and 18 yrs of age, including children treated in both the pediatric
      intensive care unit and neonatal intensive care unit. Indications for
      extracorporeal life support included both cardiac and pulmonary failure.
      INTERVENTIONS: Data analysis of patients who were treated with hemofiltration
      while on extracorporeal life support. Hemofiltration includes both
      ultrafiltration and hemofiltration with countercurrent dialysis. MEASUREMENTS AND
      MAIN RESULTS: Thirty-five patients with a mean age of 39 +/- 65 months (median, 3
      months) underwent hemofiltration while on extracorporeal life support. Forty
      three percent survived to hospital discharge (95% CI, 26%-60%). All deaths
      occurred in the intensive care unit. Recovery of renal function occurred in 93%
      of survivors (95% CI, 79%-108%). Mean duration of hemofiltration in survivors,
      including time during and after extracorporeal life support, was 9 +/- 6 days.
      All nonsurvivors were on renal replacement therapy at the time of death. In this
      analysis, decreased survival was significantly associated with the use of
      vasopressor infusions (p =.01) and the presence of complications (p =.006).
      Vasopressor infusions were required in 89% of patients, and 37% of patients
      experienced complications. CONCLUSIONS: In patients receiving hemofiltration
      while on extracorporeal life support, survival is comparable to that reported in
      other extracorporeal life support or hemofiltration populations. Decreased
      survival in these patients may be associated with the use of vasopressor
      infusions and the occurrence of complications. Recovery of renal function occurs
      in most survivors.

PMID- 12793949
TI  - Airway pressure release ventilation in pediatrics.
AB  - OBJECTIVES: The purpose of this study was to determine the effectiveness of
      airway pressure release ventilation in children. DESIGN: Prospective, randomized,
      crossover clinical trial. SETTING: This study was conducted in our 33-bed
      pediatric intensive care unit at The Children's Hospital of Philadelphia.
      PATIENTS: Patients requiring mechanical ventilatory support and weighing >8 kg
      were considered for enrollment. Patients were excluded if they required
      mechanical ventilatory support for >7 days or required >.50 Fio(2) for >7 days
      before enrollment. Patients with documented obstructive airway disease and
      congenital or acquired heart disease were excluded as well. INTERVENTIONS: Each
      patient received both volume-controlled synchronized intermittent mechanical
      ventilation (SIMV) and airway pressure release ventilation (APRV) via the Drager
      Evita ventilator (Drager, Lubeck, Germany). Measurements were obtained after the
      patient was stabilized on each ventilation mode. Stabilization was defined as
      oxygenation, ventilation, hemodynamic variables, and patient comfort within the
      acceptable range for each patient as determined by the bedside physician. After
      measurements were obtained on the initial mode of ventilation, the subjects
      crossed over to the alternative study mode. Stabilization was again achieved, and
      measurements were repeated. After completion of the second study measurements,
      patients were placed on the ventilation modality preferred by the bedside
      clinician and were followed through weaning and extubation. Measurements: Vital
      signs, airway pressures, minute ventilation, Spo(2), and E(T)CO(2) were recorded
      at enrollment and at each study condition. MAIN RESULTS: APRV provided similar
      ventilation, oxygenation, mean airway pressure, hemodynamics, and patient comfort
      as SIMV. Inspiratory airway pressures were lower with APRV when compared with
      SIMV. CONCLUSIONS: Using APRV in children with mild to moderate lung disease
      resulted in comparable levels of ventilation and oxygenation at significantly
      lower inspiratory peak and plateau pressures. Based on these findings, we plan to
      evaluate APRV in children with significant lung disease.

PMID- 12793950
TI  - Aluminum accumulation in critically ill children on sucralfate therapy.
AB  - BACKGROUND: Sucralfate, used in stress ulcer prophylaxis, contains aluminum,
      which can be absorbed from the gut. OBJECTIVE: To determine whether toxic serum
      aluminum levels can develop after short-term sucralfate therapy in critically ill
      children. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care
      unit of a pediatric university hospital. PATIENTS: Nineteen patients receiving
      mechanical ventilatory support (median age, 5 yrs [range, 0.25-16 yrs]; median
      weight, 17 kg [range, 3.5-60 kg]). INTERVENTIONS: All patients received
      sucralfate suspension nasogastrically. Measurements and RESULTS: Serum aluminum
      concentrations were measured after a short period on sucralfate therapy (median
      time, 7 days [range, 3-14 days]). There was no correlation between total
      sucralfate dose received (p =.35) or dose of sucralfate per unit of body weight
      (p =.55) and serum aluminum. Nine patients received peritoneal dialysis. Serum
      aluminum levels were higher in the nine patients who received peritoneal dialysis
      (median aluminum concentration, 2.86 &mgr;mol/L [range, 0.19-12.3 &mgr;mol/L])
      than the ten patients not dialyzed (median aluminum concentration, 0.55
      &mgr;mol/L [range, 0.18-0.94 &mgr;mol/L]) (p =.001). The peak serum creatinine
      levels were higher in the dialyzed patients (median creatinine level, 500
      &mgr;mol/L [range, 163-910 &mgr;mol/L]) than those not dialyzed (median
      creatinine level, 98 &mgr;mol/L [range, 36-415 &mgr;mol/L]) (p =.006). There was
      a trend toward correlation between peak serum creatinine and serum aluminum (p
      =.06). CONCLUSION: Aluminum accumulation occurs in children with acute renal
      failure on sucralfate, especially those receiving dialysis. If sucralfate is used
      in children in renal failure, serum aluminum concentrations should be monitored
      regularly.

PMID- 12793951
TI  - Impedance cardiographic waveforms in children: Involvement in left ventricular
      ejection time determination during anesthesia.
AB  - OBJECTIVE: The physiologic basis of the impedance cardiographic (ICG) signal is
      still a matter of debate. An accurate determination of left ventricular ejection
      time (LVET) is needed to calculate stroke volume. In children, several shapes of
      the ICG signal are observed during anesthesia or in critical care. The aim of
      this study was to determine the relationship between the shape of the ICG signal
      and various morphologic and hemodynamic determinants obtained with Doppler
      echocardiography to highlight the effect of the various shapes in the accuracy of
      LVET determination. DESIGN: Prospective study. SETTING: Pediatric surgery in a
      university hospital. PATIENTS: 103 children, ASA physical status I or II.
      INTERVENTIONS: General anesthesia for elective surgery. Measurements:
      Electrocardiography, ICG, and Doppler echocardiography were recorded
      simultaneously. Classic hemodynamic variables, such as heart rate, LVET, stroke
      volume, or systemic vascular resistance, were measured or calculated. A
      mathematical model of the ICG signal was used to determine the shape of the ICG
      signal and its potential relationship to various morphologic and hemodynamic
      determinants. The ICG signal shape was then modeled with the normalized
      amplitudes (NHA) and phase (NHP) of the three harmonics of the fundamental
      signal. Analysis was performed with a multiple correspondence analysis. RESULTS:
      ICG method LVET did not significantly correlate with LVET determined with Doppler
      or with heart rate. NHA and NHP of the ICG signal were not significantly related
      to LVET determined with Doppler or to stroke volume. NHA were linked to heart
      rate and the relative length of the cardiac diastolic period. CONCLUSION: The
      absence of relationship between LVET determined with Doppler and the main
      variables defining the shape of the ICG signal highlight the relative limit of
      stroke volume determination with ICG method. The involvement of the arterial
      compliance in the ICG signal shape can be discussed in regard to the links
      between NHA and both heart rate and the relative length of the cardiac diastolic
      period, respectively.

PMID- 12793952
TI  - The Th1 versus Th2 cytokine profile in cerebrospinal fluid after severe traumatic
      brain injury in infants and children.
AB  - OBJECTIVE: To further characterize the Th1 (proinflammatory) vs. the Th2
      (antiinflammatory) cytokine profile after severe traumatic brain injury (TBI) by
      quantifying the ventricular cerebrospinal fluid concentrations of Th1 cytokines
      (interleukin [IL]-2 and IL-12) and Th2 cytokines (IL-6 and IL-12) in infants and
      children. DESIGN: Retrospective study. SETTING: University children's hospital.
      PATIENTS: Twenty-four children hospitalized with severe TBI (admission Glasgow
      Coma Scale score, <13) and 12 controls with negative diagnostic lumbar punctures.
      INTERVENTIONS: All TBI patients received standard neurointensive care, including
      the placement of an intraventricular catheter for continuous drainage of
      cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Ventricular cerebrospinal
      fluid samples (n = 105) were collected for as long as the catheters were in place
      (between 4 hrs and 222 hrs after TBI). Cerebrospinal fluid samples were analyzed
      for IL-2, IL-4, IL-6, and IL-12 concentrations by enzyme-linked immunoassay. Peak
      and mean IL-6 (335.7 +/- 41.4 pg/mL and 259.5 +/- 37.6 pg/mL, respectively) and
      IL-12 (11.4 +/- 2.2 pg/mL and 4.3 +/- 0.8 pg/mL, respectively) concentrations
      were increased (p <.05) in children after TBI vs. controls (2.3 +/- 0.7 pg/mL and
      1.0 +/- 0.5 pg/mL) for IL-6 and IL-12, respectively. In contrast, peak and mean
      IL-2 and IL-4 concentrations were not increased in TBI children vs. controls.
      Increases in the cerebrospinal fluid concentration of IL-6 were significantly
      associated with admission Glasgow Coma Scale score of </=4 and age of </=4 yrs.
      Increases in cerebrospinal fluid IL-4 and IL-12 were associated with child abuse
      as an injury mechanism (both p </=.05 vs. accidental TBI). CONCLUSIONS: This
      study confirms that IL-6 levels are increased in cerebrospinal fluid after TBI in
      infants and children. It is the first report of increased IL-12 levels in
      cerebrospinal fluid after TBI in infants and children. Further, it is the first
      to report on IL-2 and IL-4 levels in pediatric or adult TBI. These data suggest
      that selected members of both the Th1 and Th2 cytokine families are increased as
      part of the endogenous inflammatory response to TBI. Finally, in that both IL-6
      and IL-12 (but neither IL-2 nor IL-4) can be produced by astrocytes and/or
      neurons, a parenchymal source for cytokines in the brain after TBI may be
      critical to their production in the acute phase after TBI.

PMID- 12793953
TI  - Hemodynamic changes during opening of the bridge in venoarterial extracorporeal
      membrane oxygenation.
AB  - OBJECTIVE: To investigate the cause of the hemodynamic changes occurring during
      opening of the bridge in venoarterial (VA) extracorporeal membrane oxygenation
      (ECMO). DESIGN: Prospective intervention study in animals. SETTING: Animal
      research laboratory of a university medical center. SUBJECTS: Eight anesthetized
      lambs installed on VA-ECMO. INTERVENTIONS: During VA-ECMO the bridge was randomly
      opened during 1, 2.5, 5, 7.5, 10, and 15 secs at ECMO flow rates of 500, 400,
      300, 200, 100, and 50 mL/min. Flows in the ECMO circuit between venous cannula
      and bridge and bridge and arterial cannula, mean arterial blood pressure, mean
      left carotid artery blood flow, central venous pressure, superior sagittal sinus
      pressure, inline mixed venous oxygen saturation, heart rate, and arterial oxygen
      saturation were measured continuously. Using near infrared spectrophotometry,
      changes in concentrations of cerebral oxygenated and deoxygenated hemoglobin and
      cerebral blood volume were also measured. Values during bridge opening were
      compared with values before opening. The same variables were determined with a
      roller pump on the bridge with a flow over the bridge at various flow rates.
      MEASUREMENTS AND MAIN RESULTS: Bridge opening resulted in a change of flow
      direction between venous cannula and bridge and bridge and arterial cannula. A
      biphasic response with initial decrease and secondary increase occurred in mean
      arterial blood pressure and mean left carotid artery blood flow. Central venous
      pressure, superior sagittal sinus pressure, deoxygenated hemoglobin, and cerebral
      blood volume increased, whereas cerebral oxygenated hemoglobin decreased. These
      effects occurred in each combination of ECMO flow rate and opening time. These
      effects could be abolished by installing a roller pump on the bridge.
      CONCLUSIONS: Bridge opening in VA-ECMO resulted in significant cerebral
      hemodynamic changes caused by an arteriovenous shunt over the bridge. The
      decreased cerebral perfusion pressure may contribute to the occurrence of
      cerebral ischemia, and the venous congestion may result in intracranial
      hemorrhages. These could be prevented by installing a roller pump on the bridge.

PMID- 12793954
TI  - Cytomegalovirus myocarditis in a healthy infant: Complete recovery after
      ganciclovir treatment.
AB  - OBJECTIVES: To report a case of acute myocarditis caused by cytomegalovirus
      infection in a 15-month-old immunocompetent infant completely recovered with
      ganciclovir treatment. DESIGN: Descriptive case report. SETTING: Pediatric
      intensive care unit in a general hospital. Patient: A 15-month-old healthy girl
      with acute, severe myocarditis. INTERVENTION: General supportive intensive care
      and mechanical ventilatory support, iv immunoglobulin, and iv ganciclovir.
      MEASUREMENTS AND MAIN RESULTS: Intensive supportive care including iv fluids,
      mechanical ventilatory support, diuretics (furosemide, spironolactone), digoxin,
      dobutamine, captopril, methylprednisolone, and iv immunoglobulin. Despite
      clinical stabilization, shortening fraction remained very poor at 17%. Addition
      of iv ganciclovir resulted in prompt and complete recovery of the cardiac muscle
      contractility with a shortening fraction of 35% that remained normal during a
      long follow-up period. CONCLUSIONS: Cytomegalovirus should be considered as a
      causative agent in acute myocarditis even in the normal, immunocompetent host. In
      such cases, addition of ganciclovir treatment should be strongly considered.

PMID- 12793955
TI  - Pulmonary hemosiderosis in scimitar syndrome after prolonged management of
      pulmonary hypertension.
AB  - OBJECTIVE: To report a fatal outcome from pulmonary hemosiderosis in an infant
      with scimitar syndrome after prolonged pulmonary vasodilator therapy. DESIGN:
      Case report. SETTING: A tertiary care pediatric intensive care unit. SUBJECT: An
      infant with scimitar syndrome. INTERVENTIONS: Treatment included redirection of
      anomalous right pulmonary venous drainage and closure of atrial septal defect,
      assisted ventilation via tracheostomy, and protracted nitric oxide and
      prostacyclin therapy until his death at 1 yr of age. RESULTS: Inhaled nitric
      oxide (iNO) and/or prostacyclin (PGI(2)) were administered for 6.5 months.
      Numerous echocardiograms demonstrated good control of pulmonary pressures and no
      evidence of pulmonary venous obstruction. Repeated attempts to slowly wean from
      the pulmonary vasodilators resulted in return of pulmonary pressures to systemic
      levels. Although there was no clinically apparent hemoptysis, pulmonary
      infiltrates worsened, prompting an open-lung biopsy that revealed pulmonary
      hemosiderosis. During the last 4 days of the patient's life, the pulmonary
      hypertensive crises with suprasystemic pressures and pulmonary infiltrates
      worsened regardless of aggressive vasodilator therapy with iNO, PGI(2),
      alkalinization, and isoproterenol. Vasodilator therapy was withdrawn and the
      patient rapidly died. CONCLUSION: We achieved long-term control of pulmonary
      hypertension with iNO and/or PGI(2) without apparent tachyphylaxis or other major
      reported side effects. Although pulmonary hypertension was successfully
      controlled with prolonged iNO and intravenous PGI(2) administration in this
      patient with scimitar syndrome, the patient died of hypoxemic respiratory failure
      from pulmonary hemosiderosis. Early evaluation of roentgenographic infiltrates
      for hemosiderosis and potential lung transplantation in similar patients may be
      warranted.

PMID- 12793956
TI  - Allergen immunotherapy: an effective immune-modifier.
AB  - Allergen-specific immunotherapy (IT) consists in administering gradually
      increasing doses of an allergen extract to sensitive patients. This practice
      results in ameliorating symptoms associated with the subsequent exposure to the
      causative allergen. Presently, the lack of therapies which affect the
      pathogenesis of the disease make IT the only treatment that may improve the
      natural course of allergic diseases.

PMID- 12793957
TI  - Effect of stress and other psychological factors on the pathophysiology and
      treatment of dermatoses.
AB  - Psychological factors precipitate or increase the morbidity of many dermatoses.
      There is increasing evidence that stress influences disease processes and
      contributes to the inflammation through vasoactive neuropeptides, lymphokines or
      other chemical mediators. Experimental results indicate that the endocrine,
      nervous and immune systems can no longer be considered autonomous, but involve
      complex bidirectional interactions between them. Dermatology holds a distinct
      position in psychosomatic medicine because it deals with an organ that can be
      readily seen and touched. The psychological states of anxiety, fear, shame,
      pleasure, and sexual excitation are visibly indicated by blushing, hair-rising,
      growing pale, itching or hyperhidrosis. The skin, therefore, clearly responds to
      many psychologic and stressful stimuli. As the skin is exposed to view,
      dermatoses elicit reactions from the patients' environment and the easy
      accessibility of the skin allows patients to interact directly with their
      lesions. In addition to the classic stress response involving increased levels of
      neuroendocrine hormones and autonomic neurotransmitters, stress also affects the
      immune system. Stress has been reported to cause decreased natural killer cell
      cytotoxicity, depressed mitogenic responses in lymphocytes, increased IgA levels,
      enhanced neutrophil phagocytosis and activation of interferon synthesis in
      lymphocytes. Psychodermatological syndromes can be classified according to the
      type and degree of causal relationship between the psychological etiology and the
      dermatoses. There is some overlap between the groups, but there is a satisfactory
      classification under three major headings that suggests an approach to treatment.

PMID- 12793958
TI  - Combination of methotrexate and prednizone decreases circulating concentrations
      of interleukin 1 beta and Interleukin 6 in patients with rheumatoid arthritis.
      Poor correlation of cytokine suppression with clinical improvement.
AB  - OBJECTIVE: To evaluate the effect of methotrexate (MTX) in combination with
      prednizone on cytokine levels, acute phase proteins and thiobarbituric acid
      reactive substances (TBAR--an indicator of peroxidative damage to tissue lipids)
      in the blood of rheumatoid arthritis (RA) patients and to investigate their
      associations with clinical disease activity. METHODS: We measured blood
      concentrations of interleukin-1 beta (IL-1 beta), interleukin- 6 (IL-6), TBARs
      and classical clinical and laboratory indices of disease activity in 36 RA
      subjects before and after 3 and 6 month treatment with MTX and prednizone. Only
      RA subjects who stopped any disease-modifying anti rheumatic drugs treatment for
      last 3 months were included in the study. Baseline cytokine and TBARs levels were
      compared with those obtained with 20 healthy controls. RESULTS: Compared to
      controls RA subjects had elevated levels of circulating IL-1 beta (63.3 +/- 47.6
      vs 13.7 +/- 7.8 pg/ml, p<0.01), IL-6 (147.2 +/- 76.5 vs 15.9 +/- 13.3 pg/ml,
      p<0.001) and TBARs (3.11 +/- 0.42 vs 1.34 +/- 0.45 nmol/1, p<0.001)
      concentrations. MTX in combination with prednizone improved patient clinical
      status that was accompanied by 1.96-, 1.25-, and 1.35-fold decrease in IL-1 beta,
      IL-6 and TBARs after 6 month treatment (p<0.001), respectively. Although, IL-1
      and IL-6 revealed a few correlations with classical indices of disease activity
      no association was found between patient clinical status improvement and cytokine
      changes over 6 month treatment. CONCLUSIONS: MTX in combination with prednizone
      decreases blood levels of IL-1 beta and IL-6 and inhibits the intensity of free
      radical- mediated processes in RA subjects. Monitoring of plasma concentrations
      of these cytokines could not predict the treatment efficacy.

PMID- 12793959
TI  - Protein and mRNA expression of CD56/N-CAM on follicular epithelial cells of the
      human thyroid.
AB  - In order to confirm CD56/N-CAM antigen prevalence in the human thyroid and to
      compare its expression on thyrocytes and NK cells, an expression of CD56/N-CAM
      antigen was searched for on isolated thyroid follicular cells and NK cells by
      flow cytometry. In addition, mRNA for CD56 was searched for in RNA isolated from
      human thyroid samples and few other organs using dot blot hybridization assay to
      prove the existence of mechanisms for active synthesis of the protein in
      question. The isolated cells from the follicular epithelium of 22 various
      pathological thyroid tissue specimens were examined for the expression of CD56/N
      CAM in terms of the percentage of positive cells and the mean fluorescence
      intensity (MFI). Blood lymphocytes were tested in parallel. The total RNA
      isolated from thyroid and control tissue specimens was subjected to dot-blot
      hybridization assay using CD56/N-CAM cDNA probe. All thyroid specimens expressed
      CD56/N-CAM, but the obtained values differed depending on the tissue examined and
      the CD56 antibody used. There were no significant differences between the non
      malignant thyroid cells of various histology, while cells in the carcinoma group
      had a much lower MFI, especially the median value. CD56 expression on NK cells
      from the donors' blood had a homogeneous distribution but the mean and median
      values of FI were almost three times lower than those on the thyroid cells. Dot
      blot hybridization came out positive with the RNA isolated from the thyroid
      specimens and also from the RNA isolated from the tonsil and lymph nodes, but
      came out negative with the RNA isolated from human and rat kidneys. These results
      strongly suggest that thyroid follicular epithelial cells express both protein
      and mRNA of CD56/N-CAM, thus being able to synthesis the relevant antigen. The
      protein expression seems to be affected by the malignant transformation of the
      thyroid cells. NK cells have apparently lower CD56/NCAM expression than thyroid
      cells.

PMID- 12793960
TI  - Intestinal mucosa-associated bacteria modulate rat mast cell reactivity.
AB  - It is well known that in some conditions bacteria of physiological flora of
      gastrointestinal tract may become pathogenic. Each complaint which causes injury
      of gastrointestinal wall integrity permits bacteria to penetrate the tissues and
      affect the tissue cells. Since mast cells represent one of very important and
      numerous cellular elements of the gastrointestinal tract walls, bacteria can
      exert the effects on them. Therefore, the aim of our study was to examine the
      influence of four strains of intestinal mucosa-associated bacteria--Bacteroides
      thetaiotaomicron, Bacteroides fragilis, Bifidobacterium adolescentis and
      Escherichia coli on the mast cell reactivity. Our experiments were performed in
      vitro on isolated rat peritoneal mast cells and the reactivity of these cells was
      estimated on the basis of histamine release. We used the suspensions of whole
      bacteria, killed by heating at 65 degrees C. We have noticed that the magnitude
      of bacteria-induced histamine release from mast cells was very low (up to 6.0%)
      when compared with histamine release induced with Con A, compound 48/80 and TNF
      alpha. However, all studied bacteria changed the reactivity of mast cells in
      anaphylactic (with ConA) and anaphylactoid (with compound 48/80) reactions. After
      40 min preincubation with B. thetaioataomicron, B. fragilis, B. adolescentis or
      E. coli ConA-induced histamine release was diminished up to 25%, 71%, 58% and and
      68% of maximal histamine release, respectively. Preincubation of rat mast cells
      with B. thetaioataomicron, B. fragilis, B. adolescentis or E. coli also changed
      their reactivity in anaphylactoid reaction with compound 48/80 (histamine release
      was diminished up to 70%, 63%, 63% and 60%, respectively).

PMID- 12793961
TI  - Comparison of felodipine and nitroglycerin actions on vasomotion physiology.
AB  - Felodipine is a Calcium blocker and nitroglycerin, a nitrate vasodilating agent,
      were compared. Two parameters were studied in vitro on bovine aortic media.
      Calcium uptake and vascular tone. The Calcium uptake measurement was performed by
      incubating in Krebs solution small slices of the preparation in the presence of
      45Ca. Studies on vascular tone were performed on deendothelialized bovine aortic
      rings suspended in Krebs solution. Felodipine (1nM-100microM) decreases Ca2+
      uptake and relaxes the preparation while nitroglycerin's 1nM-100microM) action is
      also inhibiting but very weak. When the preparation is stimulated by alpha 1
      adrenergic against phenylephrine 1microM, then nitroglycerin 100microM has a much
      stronger inhibiting effect on Call uptake and vascular tone than felodipine
      100microM. These results are reversed when the preparation is stimulated by
      KC165.4mM. Then felodipine 100nM exerts a strong inhibiting effect on Ca2+ uptake
      and vascular tone while nitroglycerin's 100nM inhibiting action is very weak. It
      is well known that in cases of endothelium disfunction the adrenergic stimulation
      provokes vasoconstriction and ischemia. This ischemia induces a second phase of
      vasoconstriction that is due to a depolarization provoked by the increased levels
      of extracellular K+. Felodipine is able to antagonize the consequences of such a
      depolarization. Thus, felodipine may be useful as an additional agent to
      nitroglycerin's treatment and that is the clinical message of our findings.

PMID- 12793962
TI  - Sensitisation to Aspergillus fumigatus and Penicillium notatum in laboratory
      workers.
AB  - Four workers in medical research laboratories, located in a basement level of a
      University facility equipped with a humidified air conditioning system,
      complained of cough and/or asthma and/or rhinitis during their normal working
      activities. Since exposure to toxic compounds was very low (similar to that of
      the outdoor environment) only microbiological monitoring was performed.
      Aspergillus fumigatus and Penicillium notatum were found in some laboratories.
      Eight laboratory workers (including the 4 symptomatic subjects) out of 26
      investigated were found to be atopic. Specific IgE sensitisation to Aspergillus
      fumigatus was found in the 8 atopic and in the 6 non-atopic workers, while
      Penicililum notatum was found in 7 atopic and 4 non-atopic subjects. History,
      physical examination and laboratory data excluded the presence of aspergillosis
      or allergic bronchial aspergillosis in the sensitised subjects. Our results
      suggest that evaluation of immune parameters, along with monitoring of the
      working environment, may reduce the risk of sensitisation and/or allergic
      symptoms in atopic laboratory workers.

PMID- 12793963
TI  - Clinical trials in stroke in 2002.

PMID- 12793964
TI  - Post-stroke inflammatory response: effects of stroke evolution and outcome.
AB  - Recovery after stroke is often hindered by further neurologic deterioration,
      which can affect up to 45% of patients. It has been suggested that one of the
      major causes of this neurologic deterioration may be post-ischemic cerebral
      inflammation. This review presents the basis of pathophysiologic mechanisms of
      post-stroke inflammation and discusses possible targets and routes for
      therapeutic intervention.

PMID- 12793965
TI  - New magnetic resonance imaging and computed tomography techniques for imaging of
      acute stroke.
AB  - With continued advances in acute stroke therapy, the ability to accurately assess
      the physiologic status of ischemic brain tissue and related vascular lesions has
      become increasingly important. In this review, evidence regarding the use of new
      magnetic resonance imaging and computed tomography techniques to guide
      thrombolytic therapy, diagnose stroke subtype, and detect acute hemorrhage are
      discussed in order to provide a clearer picture of the status of these
      neuroimaging techniques in the assessment of acute ischemic stroke patients.

PMID- 12793966
TI  - Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston
      criteria.
AB  - Cerebral amyloid angiopathy is a disorder in which deposition of amyloid within
      the arterial media and adventitia leads to intracerebral hemorrhage. Diagnosis
      during life has been hampered by the requirement for post-mortem examination for
      definitive diagnosis. The Boston Criteria for the diagnosis of cerebral amyloid
      angiopathy-related hemorrhage were developed in 1995 and 1996 in order to meet
      the need for a standardized set of diagnostic criteria that can be applied to
      living patients. Using a combination of clinical, radiologic, and pathologic
      data, these criteria reliably differentiate lobar intracerebral hemorrhage into
      categories of possible, probable, or definite based on the likelihood of
      underlying cerebral amyloid angiopathy. These criteria will be crucial for
      disease classification for future clinical studies.

PMID- 12793967
TI  - Antithrombotic and thrombolytic therapy for ischemic stroke.
AB  - Antithrombotic therapy is the mainstay of treatment for stroke prevention.
      Multiple antiplatelet agents are now proven options for patients at risk for
      stroke, whereas warfarin anticoagulation remains the preferred therapy for most
      patients with atrial fibrillation. Recent clinical trials have clarified the role
      of anticoagulation in acute stroke and in secondary prevention of
      noncardioembolic stroke. Intravenous tissue plasminogen activator is the only
      approved therapy for patients with acute ischemic stroke. Intra-arterial
      thrombolysis is emerging as a promising therapy in selected patients.

PMID- 12793969
TI  - Management of dyslipidemia: an update.
AB  - Despite the wealth of clinical evidence that demonstrates a reduction in the risk
      of coronary heart disease with the use of various lipid-lowering therapies, many
      patients in the United States are untreated or inadequately treated with these
      agents. Although the most recent treatment guidelines developed by the National
      Cholesterol Education Program provide detailed information regarding risk
      assessment of patients and desired lipid and lipoprotein goals, practitioners
      need to stay current on any emerging data that may have a significant impact on
      the management of patients with dyslipidemia. Over the past 2 years, the results
      of several clinical trials that may prompt the initiation of lipid-lowering
      therapy in a broader range of patients have been published. This article reviews
      the findings of these important clinical trials and provides some insight as to
      how these findings can be incorporated into clinical practice.

PMID- 12793968
TI  - Homocysteine and atherothrombosis: diagnosis and treatment.
AB  - Hyperhomocysteinemia has long been recognized as a risk factor for cardiovascular
      disease. Many cross-sectional and retrospective case-control studies have shown
      an association between elevated total homocysteine levels and coronary,
      peripheral, and cerebral vascular disease; prospective studies, however, have
      been inconsistent. Overall, there is evidence to suggest a modest association
      between elevated homocysteine levels and cardiovascular disease risk. Folate
      supplementation has been shown to reduce plasma homocysteine even when levels are
      in the normal range. Clinical studies suggest that lowering plasma homocysteine
      may improve endothelial dysfunction, a marker of atherothrombotic risk. The long
      term effects of folate supplementation on homocysteine levels and cardiovascular
      disease risk await the results of ongoing clinical trials. However, several
      recent studies suggest a benefit for reduction of plasma homocysteine levels, as
      individuals with lower homocysteine have reduced cardiovascular event rates.

PMID- 12793970
TI  - Screening for hypercoagulable syndromes following stroke.
AB  - Patients with ischemic stroke of unclear etiology are often screened for
      hypercoagulable syndromes or thrombophilias. These have been recognized to cause
      venous thrombosis, and include hereditary deficiencies of coagulation factors,
      genetic mutations, or acquired disorders. However, the majority of coagulation
      disorders are only rarely associated with ischemic stroke. The tests most
      commonly used to screen for thrombophilias comprise a complex array of assays
      that may be unreliable in various settings, including acute thrombosis,
      inflammation, and uses of medications such as anticoagulants. The diagnostic
      yield of thrombophilia tests in unselected stroke patients is very low, but may
      improve with careful selection of younger patients who have an otherwise
      undetermined cause of stroke or a history of venous thrombosis or multiple
      miscarriages. Various strategies have been developed that can guide the selection
      of patients (based on specific characteristics) and tests in the evaluation of
      thrombophilias. Although the diagnosis of thrombophilia aids in the potential
      explanation of stroke etiology, the best regimen for secondary prevention
      treatment for the majority of thrombophilias is still unknown.

PMID- 12793972
TI  - Drug-eluting stents for cardiovascular disorders.
AB  - Drug-eluting stents have emerged in recent years as a very promising therapy for
      prevention of restenosis after coronary implantation. Early randomized, clinical
      trials have suggested that stents eluting drugs, such as paclitaxel or sirolimus,
      released from polymeric and nonpolymeric coatings, are able to reduce restenosis
      in simple de novo lesions by more than 80% in comparison with bare metal stents.
      If restenosis can be indeed minimized globally by drug-eluting stents, coronary
      revascularization may expand to patients and lesions currently not considered for
      percutaneous intervention because of excessive recurrence, and may open
      possibilities for other stent-based endovascular treatments of atherosclerosis.

PMID- 12793971
TI  - Physical activity and the prevention of cardiovascular disease.
AB  - This article summarizes recent evidence on the role of physical activity in the
      prevention of overt and subclinical vascular disease. Epidemiologic data suggest
      that as little as 30 minutes per day of moderate-intensity physical activity,
      including brisk walking, reduces the incidence of clinical cardiovascular events
      in men and women. Regular exercise may also retard the progression of
      asymptomatic coronary and peripheral arteriosclerosis. Cardioprotective
      mechanisms of physical activity include reducing adiposity, blood pressure,
      diabetes incidence, dyslipidemia, and inflammation, and enhancing insulin
      sensitivity, glycemic control, fibrinolysis, and endothelial function. In a
      sedentary society such as the United States, public health initiatives that
      promote moderate increases in activity represent the optimal balance between
      efficacy and feasibility to achieve desired improvements in cardiovascular
      health.

PMID- 12793973
TI  - New advances in identifying genetic anomalies in stroke-prone probands.
AB  - The past several years have been marked by significant progress in identifying
      genetic anomalies in stroke-prone probands. These advances have occurred in both
      highly penetrant single-gene disorders and in common stroke, which is influenced
      by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to
      diagnose because of the wide range of notch 3 mutations that can cause disease,
      but a new immunohistochemical technique using a skin biopsy sample appears to be
      highly sensitive and specific. In a landmark Icelandic study, linkage was
      established between stroke and a locus on chromosome 5q12 designated STRK1.
      Association studies continue to identify polymorphisms that predispose to stroke
      and to markers for cerebrovascular atherosclerosis, such as intima-media
      thickness. Intense interest now surrounds genes involved in inflammation,
      including genes that encode for the interleukin-1 receptor antagonist and
      paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment
      will incorporate genetic data to refine and individualize management of
      cerebrovascular disease.

PMID- 12793975
TI  - Neuroprotection in hypothermia linked to redistribution of oxygen in brain.
AB  - Hypothermia improves the outcome of acute ischemic stroke, traumatic injury, and
      inflammation of brain tissue. We tested the hypothesis that hypothermia reduces
      the energy metabolism of brain tissue to a level that is commensurate with the
      prevailing blood flow and hence allows adequate distribution of oxygen to the
      entire tissue. To determine the effect of 32 degrees C hypothermia on brain
      tissue, we measured the sequential changes of physiological variables by means of
      PET in pigs. Cerebral blood flow and oxygen consumption (cerebral metabolic rate
      of oxygen) declined to 50% of the baseline in 3 and 5 h, respectively, thus
      elevating the oxygen extraction fraction to 140% of the baseline at 3 h. The
      results are consistent with the claim that cooling of the brain to 32 degrees C
      couples both energy metabolism and blood flow to a lower rate of work of the
      entire tissue.

PMID- 12793974
TI  - Dietary factors in atherogenesis.
AB  - Emerging evidence continues to increase our awareness of the complexity of
      pathologic processes involved in atherogenesis. Dietary modulation exclusively
      targeting cholesterol consumption is rapidly becoming an archaic mode of
      intervention as alternative theories of atherogenesis evolve. The interaction of
      nutrients that occurs with different dietary patterns has been the subject of
      intense research. Similarly, the effect of diet on vascular reactivity, lipid
      metabolic kinetics, and antioxidant potential has enormous implications for
      therapeutic modalities targeting atherosclerosis. Many dietary strategies aimed
      at inhibiting and preventing atherogenesis have resulted from ongoing research.
      Consensus opinions extrapolated from available data have also emerged.
      Regardless, the precise role of dietary modulation in atherogenesis is yet to be
      fully elucidated. This article reviews recent evidence relating to the interface
      between dietary factors and biologic models of atherogenesis. Clinical
      implications and practical applications are also discussed.

PMID- 12793976
TI  - Endothelial cell signaling during conducted vasomotor responses.
AB  - ACh and KCl stimulate vasomotor responses that spread rapidly and bidirectionally
      along arteriole walls, most likely via spread of electric current or Ca2+ through
      gap junctions. We examined these possibilities with isolated, cannulated, and
      perfused hamster cheek pouch arterioles (50- to 80-microm resting diameter).
      After intraluminal loading of 2 microM fluo 3 to measure Ca2+ or 1 microM di-8
      ANEPPS to measure membrane potential, photometric techniques were used to
      selectively measure changes in intracellular Ca2+ concentration ([Ca2+]i) or
      membrane potential in endothelial cells. Activation of the endothelium by
      micropipette application of ACh (10-4 M, 1.0-s pulse) to a short segment of
      arteriole (100-200 microm) increased endothelial cell [Ca2+]i and caused
      hyperpolarization at the site of stimulation. This response was followed rapidly
      by vasodilation of the entire arteriole ( approximately 2-mm length). Change in
      membrane potential always preceded dilation, both at the site of stimulation and
      at distant sites along the arteriole. In contrast, an increase in endothelial
      cell [Ca2+]i was observed only at the application site. Micropipette application
      of KCl, which can depolarize both smooth muscle and endothelial cells (250 mM,
      2.5-s pulse), also caused a rapid, spreading response consisting of
      depolarization followed by vasoconstriction. With KCl stimulation, in addition to
      changes in membrane potential, increases in endothelial cell [Ca2+]i were
      observed at distant sites not directly exposed to KCl. The rapid longitudinal
      spread of both hyperpolarizing and depolarizing responses support electrical
      coupling as the mode of signal transmission along the arteriolar length. In
      addition, the relatively short distance between heterologous cell types enables
      the superimposed radial Ca2+ signaling between smooth muscle and endothelial
      cells to modulate vasomotor responses.

PMID- 12793977
TI  - Differential modulation of glucose, lactate, and pyruvate oxidation by insulin
      and dichloroacetate in the rat heart.
AB  - Despite the fact that lactate and pyruvate are potential substrates for energy
      production in vivo, our understanding of the control and regulation of
      carbohydrate metabolism is based principally on studies where glucose is the only
      available carbohydrate. Therefore, the purpose of this study was to determine the
      contributions of lactate, pyruvate, and glucose to energy production in the
      isolated, perfused rat heart over a range of insulin concentrations and after
      activation of pyruvate dehydrogenase with dichloroacetate (DCA). Hearts were
      perfused with physiological concentrations of [1-13C]glucose, [U-13C]lactate, [2
      13C]pyruvate, and unlabeled palmitate for 45 min. Hearts were freeze clamped, and
      13C NMR glutamate isotopomer analysis was performed on tissue extracts. Glucose,
      lactate, and pyruvate all contributed significantly to myocardial energy
      production; however, in the absence of insulin, glucose contributed only 25-30%
      of total pyruvate oxidation. Even under conditions where carbohydrates
      represented >95% of substrate entering the tricarboxylic acid (TCA) cycle, we
      found that glucose contributed at most 50-60% of total carbohydrate oxidation.
      Despite being present at only 0.1 mM, pyruvate contributed between approximately
      10% and 30% of total acetyl-CoA entry into the TCA cycle. We also found that
      insulin and DCA not only increased glucose oxidation but also exogenous pyruvate
      oxidation; however, lactate oxidation was not increased. The differential effects
      of insulin and DCA on pyruvate and lactate oxidation provide further evidence for
      compartmentation of cardiac carbohydrate metabolism. These results may have
      important implications for understanding the mechanisms underlying the beneficial
      effects of increasing cardiac carbohydrate metabolism.

PMID- 12793978
TI  - In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens
      QT interval in mice with long QT phenotype.
AB  - Mutations in cardiac voltage-gated K+ channels cause long QT syndrome (LQTS) and
      sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by
      overexpression of a truncated K+ channel in the heart and investigated whether
      the dominant negative effect of the transgene would be overcome by the direct
      injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the
      myocardium. End points at 3-10 days included electrophysiology in isolated
      cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and
      in vivo optical mapping of action potentials and repolarization gradients in
      Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4
      aminopyridine-sensitive outward K+ current, shortened the action potential
      duration, eliminated early afterdepolarizations, shortened the QT interval,
      decreased dispersion of repolarization, and increased the heart rate. Each of
      these changes is consistent with a physiologically significant primary effect of
      adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.

PMID- 12793979
TI  - Effects of fatty acids in isolated mitochondria: implications for ischemic injury
      and cardioprotection.
AB  - Fatty acids accumulate during myocardial ischemia and are implicated in ischemia
      reperfusion injury and mitochondrial dysfunction. Because functional recovery
      after ischemia-reperfusion ultimately depends on the ability of the mitochondria
      to recover membrane potential (DeltaPsim), we studied the effects of fatty acids
      on DeltaPsim regulation, cytochrome c release, and Ca2+ handling in isolated
      mitochondria under conditions that mimicked aspects of ischemia-reperfusion. Long
      chain but not short-chain free fatty acids caused a progressive and reversible
      (with BSA) increase in inner membrane leakiness (proton leak), which limited
      mitochondrial ability to support DeltaPsim. In comparison, long-chain activated
      fatty acids promoted 1). a slower depolarization that was not reversible with
      BSA, 2). cytochrome c loss that was unrelated to permeability transition pore
      opening, and 3). inhibition of the adenine nucleotide translocator. Together,
      these results impaired both mitochondrial ATP production and Ca2+ handling.
      Diazoxide, a selective opener of mitochondrial ATP-dependent potassium (KATP)
      channels, partially protected against these effects. These findings indicate that
      long-chain fatty acid accumulation during ischemia-reperfusion may predispose
      mitochondria to cytochrome c loss and irreversible injury and identify a novel
      cardioprotective action of diazoxide.

PMID- 12793980
TI  - Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric
      arteries from diabetic rats.
AB  - In isolated superior mesenteric artery rings from age-matched control rats and
      streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in
      endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh
      induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic
      rats than in control rats, and in both groups of rats it was attenuated by
      18alpha-glycyrrhetinic acid (18alpha-GA), an inhibitor of gap junctions, and
      enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF
      type responses were very similar in magnitude between diabetic and age-matched
      control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3
      selective inhibitor, but not by Ro 20-1724, a PDE4-selective inhibitor. The
      expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were
      significantly increased in STZ-induced diabetic rats, but those for PDE4D were
      not. We conclude that the impairment of EDHF-type relaxations in STZ-induced
      diabetic rats may be attributed to a reduction in the action of cAMP via
      increased PDE activity.

PMID- 12793981
TI  - Differential effects of pulsatile versus steady flow on coronary endothelial
      membrane potential.
AB  - Steady shear stress stimulates transient hyperpolarization coupled to calcium
      sensitive potassium (KCa) channels and sustained depolarization linked to
      chloride-selective channels. Physiological flow is pulsatile not static, and
      whereas in vivo data suggest phasic shear stress may preferentially activate KCa
      channels, its differential effects on both currents remain largely unknown. To
      determine this interaction, coronary endothelial cells were cultured in glass
      capillary flow tubes, loaded with the voltage-sensitive dye bis-(1,3
      dibutylbarbituric acid)trimethine oxonol, and exposed to constant or pulsatile
      shear stress. The latter was generated by a custom servoperfusion system
      employing physiological pressure and flow waveforms. Steady shear induced a
      sustained depolarization inhibited by the Cl- channel blocker DIDS. Even after
      exposure to steady flow, subsequent transition to pulsatile shear stress further
      stimulated DIDS-sensitive depolarization. DIDS pretreatment "unmasked" a
      pulsatile flow-induced hyperpolarization of which magnitude was further enhanced
      by nifedipine, which augments epoxygenase synthesis. Pulse-shear
      hyperpolarization was fully blocked by KCa channel inhibition (charybdotoxin +
      apamin), although these agents had no influence on membrane potential altered by
      steady flow. Thus KCa-dependent hyperpolarization is preferentially stimulated by
      pulsatile over steady flow, whereas both can stimulate Cl--dependent
      depolarization. This supports studies showing greater potency of pulsatile flow
      for triggering KCa-dependent vasorelaxation.

PMID- 12793982
TI  - High-sodium intake prevents pregnancy-induced decrease of blood pressure in the
      rat.
AB  - Despite an increase of circulatory volume and of renin-angiotensin-aldosterone
      system (RAAS) activity, pregnancy is paradoxically accompanied by a decrease in
      blood pressure. We have reported that the decrease in blood pressure was
      maintained in pregnant rats despite overactivation of RAAS following reduction in
      sodium intake. The purpose of this study was to evaluate the impact of the
      opposite condition, e.g., decreased activation of RAAS during pregnancy in the
      rat. To do so, 0.9% or 1.8% NaCl in drinking water was given to nonpregnant and
      pregnant Sprague-Dawley rats for 7 days (last week of gestation). Increased
      sodium intakes (between 10- and 20-fold) produced reduction of plasma renin
      activity and aldosterone in both nonpregnant and pregnant rats. Systolic blood
      pressure was not affected in nonpregnant rats. However, in pregnant rats, 0.9%
      sodium supplement prevented the decreased blood pressure. Moreover, an increase
      of systolic blood pressure was obtained in pregnant rats receiving 1.8% NaCl. The
      0.9% sodium supplement did not affect plasma and fetal parameters. However, 1.8%
      NaCl supplement has larger effects during gestation as shown by increased plasma
      sodium concentration, hematocrit level, negative water balance, proteinuria, and
      intrauterine growth restriction. With both sodium supplements, decreased AT1 mRNA
      levels in the kidney and in the placenta were observed. Our results showed that a
      high-sodium intake prevents the pregnancy-induced decrease of blood pressure in
      rats. Nonpregnant rats were able to maintain homeostasis but not the pregnant
      ones in response to sodium load. Furthermore, pregnant rats on a high-sodium
      intake (1.8% NaCl) showed some physiological responses that resemble
      manifestations observed in preeclampsia.

PMID- 12793984
TI  - The kallikrein-kinin and the renin-angiotensin systems have a multilayered
      interaction.
AB  - Understanding the physiological role of the plasma kallikrein-kinin system (KKS)
      has been hampered by not knowing how the proteins of this proteolytic system,
      when assembled in the intravascular compartment, become activated under
      physiological conditions. Recent studies indicate that the enzyme
      prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein
      activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin
      angiotensin system (RAS) indicates a novel interaction between these two systems.
      This interaction, along with the roles of angiotensin converting enzyme, cross
      talk between bradykinin and angiotensin-(1-7) action, and the opposite effects of
      activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma
      KKS counterbalances the RAS. This review examines the interaction and cross talk
      between these two protein systems. This analysis suggests that there is a
      multilayered interaction between these two systems that are important for a wide
      array of physiological functions.

PMID- 12793983
TI  - Protein kinase C-delta mediates adenosine A3 receptor-induced delayed
      cardioprotection in mouse.
AB  - We investigated the role of protein kinase C in adenosine A3 receptor (A3AR)
      induced delayed cardioprotection in the mouse heart. Mice were treated with
      selective A3AR agonist N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA).
      Twenty-four hours later, hearts were perfused in the Langendorff mode and
      subjected to 30 min of global ischemia and 30 min of reperfusion. Infarct size
      was determined by computer morphometry of tetrazolium-stained sections, and
      ventricular function was monitored by inserting a fluid-filled balloon into the
      left ventricle (LV). Chelerythrine chloride (CHE, 5.0 mg/kg) and rottlerin (Rot,
      0.3 mg/kg) were given 30 min before IB-MECA to block total and PKC-delta
      isoforms, respectively. IB-MECA caused postischemic reduction in necrosis and
      improvement in ventricular function, which was abolished by CHE. Western blot
      analysis demonstrated translocation of the PKC-delta isoform but not the alpha,
      epsilon, xi, eta isoform(s) from cytoplasm to the membrane fraction after 30 min
      of IB-MECA administration. A3AR antagonist MRS-1191 and CHE blocked the
      translocation of PKC-delta. Furthermore, IB-MECA-induced increase in nuclear
      factor-kappaB binding was diminished by CHE. These results provide direct
      evidence of an essential role of PKC, and more specifically, PKC-delta in A3AR
      induced delayed cardioprotection.

PMID- 12793985
TI  - Body sodium and volume homeostasis.

PMID- 12793986
TI  - Neurochemical control and reconfiguration of the medullary network controlling
      different oromotor behaviors.

PMID- 12793987
TI  - Neuronal nicotinic receptors: filling the void?

PMID- 12793988
TI  - Modulation of renal microvascular function by adenosine.

PMID- 12793989
TI  - Angiotensin II receptor expression: from maturation to pathogenesis.

PMID- 12793990
TI  - Cerebral ischemia in heme oxygenase-2-deficient mice: the second filament makes
      the difference.

PMID- 12793991
TI  - Pain: new insights, new treatments?

PMID- 12793992
TI  - Broken circadian clocks: a clock gene mutation and entrainment by feeding.

PMID- 12793993
TI  - Attenuated renovascular constrictor responses to angiotensin II in adenosine 1
      receptor knockout mice.
AB  - In the present experiments we examined the renovascular constrictor effects of
      ANG II in the chronic and complete absence of A1 adenosine receptors (A1AR) using
      mice with targeted deletion of the A1AR gene. Glomerular filtration rate (GFR)
      was not different between A1AR +/+ and A1AR -/- mice under control conditions
      (450.5 +/- 60 vs. 475.2 +/- 62.5 microl/min) but fell significantly less in A1AR 
      /- mice during infusion of ANG II at 1.5 ng/min (A1AR +/+: 242 +/- 32.5
      microl/min, A1AR -/-: 371 +/- 42 microl/min; P = 0.03). Bolus injection of 1, 10,
      and 100 ng of ANG II reduced renal blood flow and increased renal vascular
      resistance significantly more in A1AR +/+ than in A1AR -/- mice. Perfused
      afferent arterioles isolated from A1AR +/+ mice constricted in response to bath
      ANG II with an EC50 of 1.5 +/- 0.4 x 10(-10) mol/l, whereas a right shift in the
      dose-response relationship with an EC50 of 7.3 +/- 1.2 x 10(-10) mol/l (P < 0.05)
      was obtained in arterioles from A1AR -/- mice (P < 0.05). The expression of AT1A
      receptor mRNA was not different in kidney RNA from A1AR +/+ or A1AR -/- mice. We
      conclude that chronic A1AR deficiency diminishes the effectiveness of ANG II to
      constrict renal resistance vessels and to reduce GFR.

PMID- 12793994
TI  - Governance of arteriolar oscillation by ryanodine receptors.
AB  - To investigate the role of ryanodine receptors in glomerular arterioles,
      experiments were performed using an isolated perfused hydronephrotic kidney
      model. In the first series of studies, BAYK-8644 (300 nM), a calcium agonist,
      constricted afferent (19.6 +/- 0.6 to 17.6 +/- 0.5 microm, n = 6, P < 0.01) but
      not efferent arterioles. Furthermore, BAYK-8644 elicited afferent arteriolar
      oscillatory movements. Subsequent administration of nifedipine (1 microM)
      inhibited both afferent arteriolar oscillation and constriction by BAYK-8644 (to
      19.4 +/- 0.5 microm). In the second group, although BAYK-8644 constricted
      afferent arterioles treated with 1 microM of thapsigargin (19.7 +/- 0.6 to 16.8
      +/- 0.6 microm, n = 5, P < 0.05), it failed to induce rhythmic contraction.
      Removal of extracellular calcium with EGTA (2 mM) reversed BAYK-8644-induced
      afferent arteriolar constriction (to 20.0 +/- 0.5 microm). In the third series of
      investigations, ryanodine (10 microM) but not 2-aminoethoxyphenyl borate (100
      microM) abolished afferent arteriolar vasomotion by BAYK-8644. In the fourth
      series of experiments, in the presence of caffeine (1 mM), the stronger
      activation of voltage-dependent calcium channels by higher potassium media
      resulted in greater afferent arteriolar constriction and faster oscillation. Our
      results indicate that L-type calcium channels are rich in preglomerular but not
      postglomerular microvessels. Furthermore, the present findings suggest that
      either prolonged calcium influx through voltage-dependent calcium channels (BAYK
      8644) or sensitized ryanodine receptors (caffeine) is required to trigger
      periodic calcium release through ryanodine receptors in afferent arterioles.

PMID- 12793995
TI  - Differential role of PTK and ERK MAPK in superoxide impairment of K(ATP) and
      K(Ca) channel cerebrovasodilation.
AB  - Previously, superoxide (O2 -) has been observed to impair pial artery dilation
      (PAD) to activators of the ATP-sensitive (KATP) and calcium-sensitive (KCa) K+
      channels. This study tested the hypothesis that activation of protein tyrosine
      kinase (PTK) and the ERK isoform of MAPK by O2 - contribute to impairment of KATP
      and KCa channel PAD. Exposure of the cerebral cortex to a xanthine oxidase O2 -
      generating system (OX) blunted PAD to cromakalim, a KATP agonist, but
      preadministration of genistein, a PTK antagonist, or U-0126, an ERK MAPK
      inhibitor, almost completely prevented such impairment (11 +/- 1 and 22 +/- 1 vs.
      3 +/- 1 and 7 +/- 1 vs. 10 +/- 1 and 16 +/- 2% for cromakalim with 10-8 and 10-6
      M PAD during control, OX, and OX + genistein conditions). In contrast, neither
      genistein nor U-0126 robustly protected PAD to NS-1619, a KCa agonist, after OX
      exposure (11 +/- 1 and 18 +/- 2 vs. 1 +/- 1 and 2 +/- 1 vs. 4 +/- 1 and 6 +/- 1%
      for 10-8 and 10-6 M NS-1619 during control, OX, and OX + genistein conditions).
      These data show that PTK and ERK MAPK activation contribute to O2 --induced KATP
      and KCa channel PAD impairment and suggest a differential greater role for PTK
      and ERK MAPK in KATP vs. KCa channel PAD impairment.

PMID- 12793996
TI  - Prolonged aspirin inhibition of anodal vasodilation is not due to the trafficking
      delay of neural mediators.
AB  - We previously reported that forearm vasodilation to a delivered all-at-once over
      5 min or a 1-min repeated monopolar anodal 0.10-mA current application is aspirin
      sensitive and that a single high-dose aspirin exerts a long-lived effect in the
      former case. We hypothesized that 1) in the latter case, the effect of aspirin
      would also be long lived and 2) the time required to resupply nerve endings with
      unblocked cyclooxygenase through axonal transport could explain this phenomenon.
      We studied the time course for the recovery of vasodilation to repeated current
      application after placebo or 1-g aspirin treatment. We then searched for a
      difference at a proximal vs. distal site in the recovery of the response. Aspirin
      abolished current-induced vasodilation at 2 h, 10 h, and 3 days, with a
      progressive recovery thereafter, but no difference between distal and proximal
      site was observed for the recovery of the response. This suggests that, although
      neural cyclooxygenase could participate in the response, the time course of
      aspirin inhibition of current-induced cutaneous vasodilation is not due to the
      time required through neural transport to resupply nerve endings with unblocked
      proteins.

PMID- 12793997
TI  - Control of glyceroneogenic activity in rat brown adipose tissue.
AB  - Brown adipose tissue (BAT) glyceroneogenesis was evaluated in rats either fasted
      for 48 h or with streptozotocin-diabetes induced 3 days previously or adapted for
      20 days to a high-protein, carbohydrate-free (HP) diet, conditions in which BAT
      glucose utilization is reduced. The three treatments induced an increase in BAT
      glyceroneogenic activity, evidenced by increased rates of incorporation of [1
      14C]pyruvate into triacylglycerol (TAG)-glycerol in vitro and a marked, threefold
      increase in the activity of BAT phosphoenolpyruvate carboxykinase (PEPCK). BAT
      glycerokinase activity was not significantly affected by fasting or diabetes.
      After unilateral BAT denervation of rats fed either the HP or a balanced diet,
      glyceroneogenesis activity increased in denervated pads, evidenced by increased
      rates of nonglucose carbon incorporation into TAG-glycerol in vivo (difference
      between 3H2O and [14C]glucose incorporations) and of [1-14C]pyruvate in vitro.
      PEPCK activity was not significantly affected by denervation. The data suggest
      that BAT glyceroneogenesis is not under sympathetic control but is sensitive to
      hormonal/metabolic factors. In situations of reduced glucose use there is an
      increase in BAT glyceroneogenesis that may compensate the decreased generation of
      glycerol-3-phosphate from the hexose.

PMID- 12793998
TI  - Relationship between blood pressure, sleep K-complexes, and muscle sympathetic
      nerve activity in humans.
AB  - Stage 2 sleep is characterized by the EEG appearance of "K-complexes" and blood
      pressure oscillations. K-complexes may be directly related to blood pressure
      changes or they may reflect central sympathetic activation. We analyzed the
      temporal relationship among K-complexes, heart rate (HR), blood pressure (BP),
      and muscle sympathetic nerve activity (MSNA) during sleep in eight healthy
      volunteers (3 men and 5 women, age 22-41 yr). Most K-complexes presented as
      single large complexes (56 +/- 20%), followed by single small complexes (15 +/-
      14%) and as couplets or triplets (13 +/- 6%). Single large K-complexes were
      preceded by a baroreflex-mediated increase of MSNA in approximately one-half
      (55%) of the cases. Detailed analysis of HR, BP, and MSNA was possible in 63
      (45%) large single K-complexes not disturbed by preceding baroreflex-related
      changes. Systolic and diastolic BP and MSNA increased significantly after single
      events (22.5 +/- 13, 5.2 +/- 2.1, and 6.5 +/- 3.0%). Mean sympathetic baroreflex
      latency was similar after the single large K-complexes compared with the mean
      value during stage 2 sleep (1,290 +/- 126 vs. 1,279 +/- 61 ms). The area under
      the burst was significantly increased after single large K-complexes (median 3.9
      vs. 9.0 arbitrary units, P < 0.03). The results support the hypothesis that K
      complexes express cortical activation leading to temporary facilitation of
      sympathetic outflow in a graded fashion. Their functional effects appear to be
      independent of baroreflex modulation of MSNA in approximately 50% of the cases.

PMID- 12793999
TI  - Direct interstitial infusion of NK1-targeted neurotoxin into the spinal cord: a
      computational model.
AB  - Convection-enhanced delivery of substance P (SP) nocitoxins to the spinal cord
      interstitium is under consideration for the treatment of chronic pain. To
      characterize treatment protocols, a three-dimensional finite-element model of
      infusion into the human dorsal column was developed to predict the distribution
      of SP-diphtheria toxin fusion protein (SP-DT') within normal and target tissue.
      The model incorporated anisotropic convective and diffusive transport through the
      interstitial space, hydrolysis by peptidases, and intracellular trafficking. For
      constant SP-DT' infusion (0.1 microl/min), the distribution of cytotoxicity in
      NK1 receptor-expressing neurons was predicted to reach an asymptotic limit at 6-8
      h in the transverse direction at the level of the infusion cannula tip (
      approximately 60% ablation of target neurons in lamina I/II). Computations
      revealed that SP-DT' treatment was favored by a stable SP analog (half-life
      approximately 60 min), high infusate concentration (385 nM), and careful catheter
      placement (adjacent to target lamina I/II). Sensitivity of cytotoxic regions to
      NK1 receptor density and white matter protease activity was also established.
      These data suggest that intraparenchymal infusions can be useful for treatment of
      localized chronic pain.

PMID- 12794000
TI  - Dynamics of sympathetic baroreflex control of arterial pressure in rats.
AB  - By a white noise approach, we characterized the dynamics of the sympathetic
      baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic
      nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus
      baroreceptor pressure (BRP) was altered randomly. We estimated the transfer
      functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical
      arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc
      gradually increased about threefold as the frequency of BRP change increased from
      0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly
      decreased to 0.4% of the steady-state gain as the frequency increased from 0.01
      to 1 Hz. Although the total arc also had low-pass characteristics, the rate of
      attenuation in its gain was significantly slower than that of the neuromechanical
      arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish
      response of the neuromechanical arc. We conclude that the quantitative estimation
      of the baroreflex dynamics is vital for an integrative understanding of
      baroreflex function in rats.

PMID- 12794001
TI  - Sedentary behavior during postnatal life is determined by the prenatal
      environment and exacerbated by postnatal hypercaloric nutrition.
AB  - The discovery of a link between in utero experience and later metabolic and
      cardiovascular disease is one of the most important advances in epidemiology
      research of recent years. There is now increasing evidence that alterations in
      the fetal environment have long-term consequences on metabolic and endocrine
      pathophysiology in adult life. This process has been termed "fetal programming,"
      and we have shown that undernutrition of the mother during gestation leads to
      obesity, hypertension, hyperphagia, hyperinsulinemia, and hyperleptinemia in
      offspring. Using this model of maternal undernutrition throughout pregnancy, we
      investigated whether prenatal influences may lead to alterations in postnatal
      locomotor behavior, independent of postnatal nutrition. Virgin Wistar rats were
      time mated and randomly assigned to receive food either ad libitum (ad libitum
      group) or at 30% of ad libitum intake (undernourished group). Offspring from UN
      mothers were significantly smaller at birth than AD offspring. At weaning,
      offspring were assigned to one of two diets [control or hypercaloric (30% fat)].
      At ages of 35 days, 145 days, and 420 days, voluntary locomotor activity was
      assessed. At all ages studied, offspring from undernourished mothers were
      significantly less active than offspring born of normal birth weight for all
      parameters measured, independent of postnatal nutrition. Sedentary behavior in
      programmed offspring was exacerbated by postnatal hypercaloric nutrition. This
      work is the first to clearly separate prenatal from postnatal effects and shows
      that lifestyle choices themselves may have a prenatal origin. We have shown that
      predispositions to obesity, altered eating behavior, and sedentary activity are
      linked and occur independently of postnatal hypercaloric nutrition. Moreover, the
      prenatal influence may be permanent as offspring of undernourished mothers were
      still significantly less active compared with normal offspring at an advanced
      adult age, even in the presence of a healthy diet throughout postnatal life.

PMID- 12794002
TI  - Subchronic endotoxin inhalation causes persistent airway disease.
AB  - The endotoxin component of organic dusts causes acute reversible airflow
      obstruction and airway inflammation. To test the hypothesis that endotoxin alone
      causes airway remodeling, we have compared the response of two inbred mouse
      strains to subchronic endotoxin exposure. Physiological and biological parameters
      were evaluated after 1 day, 5 days, or 8 wk of exposure to endotoxin
      [lipopolysaccharide (LPS)] in endotoxin-sensitive (C3HeB/FeJ) and endotoxin
      resistant (C3H/HeJ) mice. After 5 days or 8 wk of LPS exposure, only C3HeB/FeJ
      had elevated airway hyperreactivity to inhaled methacholine. Only the C3HeB/FeJ
      mice had significant inflammation of the lower respiratory tract after 1 day, 5
      days, or 8 wk of LPS exposure. Stereological measurements of small, medium, and
      large airways indicated that an 8-wk exposure to LPS resulted in expansion of the
      submucosal area only in the C3HeB/FeJ mice. Cell proliferation as measured by
      bromodeoxyuridine incorporation contributed to the expansion of the submucosa and
      was only significantly elevated in C3HeB/FeJ mice actively exposed to LPS.
      C3HeB/FeJ mice had significantly elevated levels of interleukin-1beta protein in
      whole lung lavage after 1 day and 5 days of LPS exposure and significantly
      elevated protein levels of total and active transforming growth factor-beta1 in
      whole lung lavage fluid after 5 days of LPS exposure. Our findings demonstrate
      that subchronic inhalation of LPS results in the development of persistent airway
      disease in endotoxin-responsive mice.

PMID- 12794003
TI  - IL-13-induced changes in the goblet cell density of human bronchial epithelial
      cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation.
AB  - In addition to a direct proinflammatory role, IL-13 has been demonstrated to
      induce a goblet cell metaplastic phenotype in the airway epithelium in vivo. We
      have studied the direct effects of IL-13 (and IL-4) on well-differentiated, air
      liquid interface cultures of human bronchial epithelial cells (HBEs) and provide
      a quantitative assessment of the development of a mucus hypersecretory phenotype
      induced by these cytokines. Using Alcian blue staining of goblet cells and
      immunohistochemical detection of MUC5AC, we found that IL-13 (and IL-4) induced
      increases in the goblet cell density (GCD) of the HBE cultures. The effects of
      these cytokines were critically dependent on concentration: 1 ng/ml routinely
      induced a 5- to 10-fold increase in GCD that was associated with a hypersecretory
      ion transport phenotype. Paradoxically, 10 ng/ml of either cytokine induced a
      profound reduction in GCD. Removal of EGF from the culture media or treatment of
      the cells with AG-1478 [a potent inhibitor of EGF receptor tyrosine kinase (EGFR
      TK)] demonstrated that the EGFR-TK pathway was key to the regulation of the basal
      GCD but that it was not involved in the IL-13-driven increase. The IL-13-driven
      increase in GCD was, however, sensitive to inhibition of MEK (PD-98059, U-0126),
      p38 MAPK (SB-202190), and phosphatidylinositol (PtdIns) 3-kinase (LY-294002).
      These data support the concept that IL-13 is in part able to induce a mucus
      hypersecretory phenotype through a direct interaction with the airway epithelium
      and that MAP kinase and PtdIns 3-kinase signaling pathways are involved.

PMID- 12794004
TI  - Effects of eosinophils on nerve cell morphology and development: the role of
      reactive oxygen species and p38 MAP kinase.
AB  - The adhesion of eosinophils to nerve cells and the subsequent release of
      eosinophil products may contribute to the pathogenesis of conditions such as
      asthma and inflammatory bowel disease. In this study we have separately examined
      the consequences of eosinophil adhesion and degranulation for nerve cell
      morphology and development. Eosinophils induced neurite retraction of cultured
      guinea pig parasympathetic nerves and differentiated IMR32 cholinergic
      neuroblastoma cells. Inhibition of eosinophil adhesion to IMR32 cells attenuated
      this retraction. Eosinophil adhesion to IMR32 cells led to tyrosine
      phosphorylation of a number of nerve cell proteins, activation of p38 MAP kinase,
      and generation of neuronal reactive oxygen species (ROS). Inhibition of tyrosine
      kinases with genistein prevented both the generation of ROS in the nerve cells
      and neurite retraction. The p38 MAP kinase inhibitor SB-239063 prevented neurite
      retraction but had no effect on the induction of ROS. Thus eosinophils induced
      neurite retraction via two distinct pathways: by generation of tyrosine kinase
      dependent ROS and by p38 MAP kinase. Eosinophils also prevented neurite outgrowth
      during differentiation of IMR32 cells. In contrast to their effect on neurite
      retraction, this effect was mimicked by medium containing products released from
      eosinophils and by eosinophil major basic protein. These results indicate that
      eosinophils modify the morphology of nerve cells by distinct mechanisms that
      involve adhesion and released proteins.

PMID- 12794005
TI  - Changes in alveolar epithelial cell proportions during fetal and postnatal
      development in sheep.
AB  - Basal lung expansion is an important determinant of alveolar epithelial cell
      (AEC) phenotype in the fetus. Because basal lung expansion increases toward term
      and is reduced after birth, we hypothesized that these changes would be
      associated with altered proportions of AECs. AEC proportions were calculated with
      electron microscopy in fetal and postnatal sheep. Type I AECs increased from 4.8
      +/- 1.3% at 91 days to 63.0 +/- 3.6% at 111 days of gestation, remained at this
      level until term, and decreased to 44.8 +/- 1.8% after birth. Type II AECs
      increased from 4.3 +/- 1.5% at 111 days to 29.6 +/- 4.1% at 128 days of
      gestation, remained at this level until term, and then increased to 52.9 +/- 1.5%
      after birth. Surfactant protein (SP)-A, -B and -C mRNA levels increased with
      increasing gestational age before birth, but the changes in SP expression after
      birth were inconsistent. Thus before birth type I AECs predominate, whereas after
      birth type II AECs predominate, possibly due to the reduction in basal lung
      expansion associated with the entry of air into the lungs.

PMID- 12794006
TI  - Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR.
AB  - Antigen induces murine bronchial hyperreactivity (BHR), inflammation, mucus
      accumulation, and airway remodeling. To investigate whether leukotrienes (LT)
      mediate the effects of antigen [ovalbumin (Ova)], we studied 5-lipoxygenase (5
      LO) expression in immunized BP2 mice and blocked LT synthesis with the 5-LO
      inhibitor zileuton or antagonized their effects with receptor antagonists
      [cysteinyl leukotriene (Cys-LT)-ra MK-571, LY-171883; LTB4-ra PH-163]. Cys-LT
      content increased in the bronchoalveolar lavage fluid (BALF) as early as 15 min
      after the intratracheal instillation of Ova. Zileuton inhibited LT release in the
      BALF and eosinophil recruitment in the lungs, and dose dependently reduced BHR,
      mucus accumulation, and remodeling, as did the LT-ra. Thus LT, released just
      after antigen challenge, might constitute the first step in accounting for the
      effects of Ova. Because mucus accumulation is regulated via the EGF receptor
      (EGFR), which is also implicated in the effects of LT, we studied this pathway
      with AG-1478, an EGFR tyrosine kinase inhibitor given at 0.5, 4, and 20 mg/kg. AG
      1478 inhibited BHR, inflammation, and lung remodeling induced by Ova or by
      molecules themselves generated by Ova, such as LT, IL-13, and monocyte
      chemoattractant protein-1, which promote identical effects, suggesting the
      involvement of the EGFR pathway in the asthma-like syndrome observed.

PMID- 12794007
TI  - Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by
      inflammatory alveolar macrophages.
AB  - The phagocytosis of apoptotic inflammatory cells by alveolar macrophages (AMs) is
      a key component of inflammation resolution within the air space. Surfactant
      protein A (SP-A) has been shown to stimulate the phagocytosis of apoptotic
      neutrophils (PMNs) by normal AMs. We hypothesized that SP-A promotes the
      resolution of alveolar inflammation by enhancing apoptotic PMN phagocytosis and
      anti-inflammatory cytokine release by inflammatory AMs. Using an LPS lung
      inflammation model, we determined that SP-A stimulates the phagocytosis of
      apoptotic PMNs threefold by normal AMs and AMs isolated after LPS injury.
      Furthermore, SP-A enhances transforming growth factor-beta1 (TGF-beta1) release
      from both AM populations. Inflammatory AMs release twofold more TGF-beta1 in
      culture than do normal AMs. SP-A and apoptotic PMNs together stimulate TGF-beta1
      release equivalently from normal and inflammatory cultured AMs (330% of
      unstimulated release by normal AMs). In summary, SP-A enhances apoptotic PMN
      uptake, stimulates AM TGF-beta1 release, and modulates the amount of TGF-beta1
      released when AMs phagocytose apoptotic PMNs. These findings support the
      hypothesis that SP-A promotes the resolution of alveolar inflammation.

PMID- 12794008
TI  - Selectin-dependent rolling and adhesion of leukocytes in nicotine-exposed
      microvessels of lung allografts.
AB  - The interaction of circulating leukocytes with lung microvessels is a critical
      event in the recruitment of effector cells into the interstitial tissue during
      episodes of inflammation, including smoking-induced chronic airway disease. In
      the present study, murine lung tissue transplanted into a dorsal skinfold window
      chamber in nude mice was used as a model system to study nicotine-induced
      leukocyte trafficking in vivo. The revascularized lung microvessels were
      determined to be of pulmonary origin based on their ability to constrict in
      response to hypoxia. We demonstrated that nicotine significantly enhanced rolling
      and adhesion of leukocytes within lung microvessels comprising arterioles and
      postcapillary venules in a dose-dependent manner, but failed to induce leukocyte
      emigration. Nicotine-induced rolling and adhesion was significantly higher in
      venules than in arterioles. Treatment of mice with monoclonal antibodies (MAbs)
      against L-, E-, or P-selectin after exposure of lung allografts to nicotine
      resulted in variable but significant inhibition of nicotine-induced rolling,
      whereas nicotine-induced subsequent adhesion was inhibited by MAbs against L- and
      P-selectin but not E-selectin. Exposure of lung allografts to nicotine along with
      PD-98059, a mitogen-activated protein kinase (MAPK)-specific inhibitor, resulted
      in significant inhibition of nicotine-induced rolling and adhesion. In vitro,
      exposure of murine lung endothelial cells to nicotine resulted in increased
      phosphorylation of mitogen-activated/extracellular signal-regulated protein
      kinase 1/2, which could be blocked by PD-98059. Overall, these results suggest
      that nicotine-induced inflammation in the airways could potentially be due to
      MAPK-mediated, selectin-dependent leukocyte-endothelial cell interactions in the
      lung microcirculation.

PMID- 12794009
TI  - Intra-arterial cisplatin in osteosarcoma: same question, different answer.

PMID- 12794010
TI  - Peritoneal carcinomatosis: a final frontier.

PMID- 12794011
TI  - Achieving the lowest false-negative rate in peritumoral breast lymphatic mapping:
      the oncologic search for the Holy Grail.

PMID- 12794012
TI  - The recent past and future of adjuvant therapy for pancreatic cancer.

PMID- 12794013
TI  - Treatment of T2 gallbladder cancer.

PMID- 12794014
TI  - Other thermal ablation techniques: microwave and interstitial laser ablation of
      liver tumors.
AB  - BACKGROUND: Thermal ablation of hepatic malignancies is becoming a widespread
      treatment approach. In addition to radiofrequency ablation, microwave coagulation
      (MCT) and laser-induced interstitial thermotherapy (LITT) are being used
      clinically to treat patients with liver cancers. METHODS: The principles and
      clinical indications for MCT and LITT are described. Treatment approaches and
      results from published clinical studies are reviewed. The evolution of these
      thermal treatment modalities and limitations of currently available equipment is
      provided. RESULTS: The interstitial probes and equipment used for MCT and LITT
      for liver tumors are undergoing changes to improve treatment efficacy. Both MCT
      and LITT have been limited by the relatively small zone of coagulation produced
      with a single probe placement. Both techniques can be performed safely, and local
      recurrence and long-term survival rates are being established. CONCLUSIONS: MCT
      and LITT are two alternative thermal ablation techniques being used to treat
      patients with primary and metastatic hepatic malignancies. The utility of these
      two treatments has been limited by the relatively small area of thermal necrosis
      produced around the interstitial probes, but design modifications and new
      equipment may improve these limitations.

PMID- 12794015
TI  - Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of
      the extremity.
AB  - BACKGROUND: A protocol to treat osteosarcoma of the extremity was developed at
      two local institutions. METHODS: The study involved a dose-intensified
      neoadjuvant protocol of intravenous doxorubicin and intra-arterial cisplatin
      administered repetitively until maximum angiographic response was noted.
      Definitive surgery was delayed until > or =90% reduction in tumor neovascularity
      was documented. Prospective assessment of serial arteriograms was highly accurate
      (94%) in predicting histological response and assisted in surgical planning.
      After resection, if patients were determined to be good responders (> or =90%
      tumor necrosis), they underwent a 4-month postoperative course with the same
      agents. Poor responders (<90% necrosis) were treated with alternative agents for
      12 months from diagnosis. Forty-seven assessable patients with primary, high
      grade, nonmetastatic osteosarcoma of the extremity were included in this
      analysis. The median age was 15 years (range, 7-21 years). RESULTS: Patients
      underwent an average of four preoperative intra-arterial courses. Forty-three
      patients underwent limb-preservation procedures, and 41 had >90% tumor necrosis.
      With an average follow-up of 92 months (range, 20-178 months), 39 patients were
      continuously disease free, 3 died of disease, 1 died of other causes, and 4 have
      no evidence of disease 11 to 51 months after relapse (all pulmonary metastases).
      There were no local recurrences. Kaplan-Meier analysis demonstrated a 10-year
      overall survival of 92% and an event-free survival of 84%. CONCLUSIONS: This
      study demonstrates excellent survival with a dose-intensified neoadjuvant
      protocol. Future endeavors should involve a multi-institutional randomized study
      comparing this approach with another multiagent intravenous neoadjuvant protocol.

PMID- 12794016
TI  - Cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative
      chemotherapy for peritoneal carcinomatosis arising from colon adenocarcinoma.
AB  - BACKGROUND: Hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) has
      been recently proposed to treat peritoneal carcinomatosis arising from colon
      adenocarcinoma, which is usually regarded as a lethal clinical entity. The
      purpose of this study was to evaluate the clinical outcome of this combined
      treatment. METHODS: A retrospective study of 46 patients treated for peritoneal
      carcinomatosis from colon adenocarcinoma was performed. Thirty-four patients were
      treated with complete cytoreductive surgery immediately followed by
      intraoperative HIIC with mitomycin C and cisplatin. The clinical outcome of these
      34 patients was analyzed; the median follow-up period was 14.5 months. RESULTS:
      No postoperative deaths were reported. The postoperative morbidity rate was 35%.
      No severe locoregional or systemic toxicity was observed. The 2-year overall
      survival was 31%, and the median survival time and the median time to local
      disease progression were 18 and 13 months, respectively. Survival and local
      disease control in patients with well- and moderately differentiated colon
      adenocarcinoma were significantly better than in those with poorly differentiated
      tumors. CONCLUSIONS: Considering the dismal prognosis of this condition, HIIC
      seems to achieve encouraging results in a selected group of patients affected
      with resectable peritoneal carcinomatosis arising from colon adenocarcinoma.
      These findings support the conduction of formal phase III randomized trials.

PMID- 12794017
TI  - Intraperitoneal photodynamic therapy causes a capillary-leak syndrome.
AB  - BACKGROUND: In patients undergoing intraperitoneal (IP) photodynamic therapy
      (PDT), the combination of aggressive surgical debulking and light therapy causes
      an apparent systemic capillary-leak syndrome that necessitates significant
      intensive care unit (ICU) management after surgery. METHODS: From May 1997 to May
      2001, 65 patients underwent surgical debulking and PDT as part of an ongoing
      phase II trial for disseminated IP cancer. Perioperative data were reviewed
      retrospectively, and statistical analyses were performed to determine whether any
      identifiable factors were associated with the need for mechanical ventilation for
      longer than 1 day and with the occurrence of postoperative complications.
      RESULTS: Forty-three women and 22 men (mean age, 49 years) were treated.
      Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The
      mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and
      49 patients required blood products. Twenty-four patients were intubated for
      longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1
      day. The median ICU stay was 4 days. Overall, 110 complications developed in 45
      (69%) of the 65 patients. Significant complications included 6 patients with
      acute respiratory distress syndrome, 28 patients with infectious complications,
      and 4 patients with anastomotic complications. Statistical analyses revealed that
      surgery-related factors were significantly associated with these complication
      outcomes. CONCLUSIONS: Patients who undergo surgical debulking and IP PDT develop
      a significant capillary-leak syndrome after surgery that necessitates massive
      volume resuscitation, careful ICU monitoring, and, frequently, prolonged
      ventilatory support.

PMID- 12794018
TI  - Macroscopic quality control improves the reliability of blue dye-only sentinel
      lymph node biopsy in breast cancer.
AB  - BACKGROUND: One of the problems of sentinel lymph node (SLN) biopsy is the risk
      of false negatives. At the Institut Curie, to reduce the false-negative rate, we
      have developed a histological quality control of the SLN performed by blue dye
      alone, which consists of verification of the SLN blue stain by the pathologist.
      METHODS: A total of 324 patients underwent an SLN biopsy procedure with patent
      blue dye only followed by an immediate axillary dissection. Initially, SLNs were
      checked to ensure that they were blue by macroscopic examination. Finally, a
      search for immunohistochemistry micrometastasis was performed. RESULTS: In 277
      (85.5%) of 324 patients, an SLN was identified by the surgeon. After standard
      examination, the false-negative rate was 11.1% (10 of 90). After macroscopic
      checking of the 197 negative SLNs, 167 of the 197 were confirmed blue, and there
      were 5 false negatives, which brought the false-negative rate down to 5.6% (5 of
      90). Sixty SLNs out of the 167 confirmed blue SLNs were then proved to be
      immunohistochemically micrometastatic, and there were 3 false negatives, giving a
      final false-negative rate of 2.2% (2 of 90; P =.002). CONCLUSIONS: In this
      series, the procedure of pathologic analysis of the SLN has resulted in a
      significant reduction of the false-negative rate.

PMID- 12794019
TI  - Lymphoseek: a molecular radiopharmaceutical for sentinel node detection.
AB  - BACKGROUND: Lymphoseek is a new radiopharmaceutical that accumulates in lymphatic
      tissue by binding to a receptor that resides on the surface of macrophage cells.
      We conducted a phase I clinical trial in which Lymphoseek was compared with
      filtered [(99m)Tc]sulfur colloid (fTcSC) for sentinel node detection in patients
      with breast cancer. METHODS: Twelve women (42-71 years) with breast cancer were
      randomly assigned to a 3-hour imaging protocol with peritumoral/subdermal
      injections (.5 mCi) of either Lymphoseek (1 nmol; molecular weight, 28 kDa;
      diameter,.007 micro m) or.2 micro m of fTcSC. Serial images were acquired for 180
      minutes. Sentinel nodes, excised within 4.2 to 7.3 hours of administration, were
      assayed in a dose calibrator. RESULTS: The receptor-binding agent, Lymphoseek,
      exhibited a significantly (P =.0025) faster injection site clearance (rate,.255
      +/-.147/hour; fTcSC rate,.014 +/-.018/hour); the mean Lymphoseek clearance half
      time was 2.72 +/- 1.57 hours compared with 49.5 +/- 38.5 hours for fTcSC. The
      primary sentinel node uptake of Lymphoseek (range,.02%-1.12%; mean,.55% +/-.43%)
      and fTcSC (range,.00%-1.93%; mean,.65% +/-.63%) did not differ (P =.75).
      Lymphoseek exhibited a lower mean number of sentinel nodes per study (n = 1.3)
      than fTcSC (n = 1.7) and a higher concordance with Lymphazurin. CONCLUSIONS: The
      molecular receptor-binding agent Lymphoseek demonstrated faster injection site
      clearance and equivalent primary sentinel node uptake when compared with fTcSC.

PMID- 12794020
TI  - Should adjuvant therapy remain the standard of care for patients with resected
      adenocarcinoma of the pancreas?
AB  - Adenocarcinoma of the pancreas continues to be a formidable disease. In the
      United States, patients who have had resected disease are generally offered
      adjuvant chemoradiation. The current National Comprehensive Cancer Network
      practice guidelines uniformly support this practice. We reviewed seven selected
      series to evaluate the efficacy of adjuvant therapy for patients who had resected
      adenocarcinoma of the pancreas. Current evidence-based analysis demonstrates that
      an adjuvant therapy regimen as a standard of care is lacking. We, therefore,
      believe that it should be used judiciously because its benefit is confined to
      only a fraction of patients treated by complete resection (R0); patients with
      residual microscopic disease (R1) derived negligible benefits. Given the
      financial constraints and the small effect that current therapies have on this
      fatal disease, clinicians should concentrate on developing novel therapies and
      new paradigms to address this age-old problem.

PMID- 12794021
TI  - An experimental study on the pharmacokinetics of 5-fluorouracil regional
      chemotherapy for pancreatic cancer.
AB  - BACKGROUND: Recently a few centers reported promising results of regional intra
      arterial chemotherapy for pancreatic cancer. However, the detailed
      pharmacokinetics and the side effects of anticancer agents remain unclear.
      METHODS: Catheters were introduced into the gastroduodenal artery and the splenic
      artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was
      performed over 10 minutes. In group II, 5-FU was infused systemically. In group
      III, an intra-arterial infusion was repeated weekly three times. Blood samples
      and liver and pancreas tissue samples were obtained to determine 5-FU levels. In
      a subset of each group, the pancreas, duodenum, and liver were excised for
      histological analyses. RESULTS: Immediately after the infusion of 5-FU, the
      portal level in group I was higher than that in group II. However, the mean
      systemic level in group I was lower than in group II. The mean tissue
      concentration in the pancreas in group I was significantly higher than that of
      group II. Histological examination revealed no microscopic alterations after
      treatment in all groups, including group III. CONCLUSIONS: This fundamental study
      suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows
      higher regional drug delivery without adverse effects on normal regions of the
      pancreas, the duodenum, and the liver.

PMID- 12794022
TI  - Squamous cell carcinoma of the head and neck in nonsmokers and nondrinkers: an
      analysis of clinicopathologic characteristics and treatment outcomes.
AB  - BACKGROUND: The objective of this study was to describe the clinicopathologic
      manifestations of disease and outcomes of treatment among individuals without a
      history of smoking tobacco or consuming alcohol who develop head and neck cancer.
      METHODS: Of 1648 invasive head and neck cancer cases treated between 1970 and
      2001 at Roswell Park Cancer Institute, 40 patients were identified as never
      having smoked tobacco or consumed alcohol during their lifetime. These cases were
      reviewed to gather data on multiple clinicopathologic variables. RESULTS: Mean
      age at presentation of nonsmoker/nondrinker head and neck cancer patients was 60
      years (range, 27 to 90 years), and 78% (n = 31) of the patients were women. The
      distributions of tumor sites were 75.0% oral cavity (n = 30), 20.0% oropharynx (n
      = 8), and 5.0% larynx (n = 2). Sixteen patients (40%) experienced a recurrence of
      disease during the follow-up period, and 10 patients (25.0%) developed a second
      primary tumor a median of 6 years after their initial diagnosis. CONCLUSIONS: The
      nonsmoker/nondrinker head and neck cancer patient tends to be elderly and female,
      have oral cavity primary tumors, and be predisposed to second primary tumor
      development.

PMID- 12794023
TI  - Role of sentinel lymph node biopsy in patients with thin (<1 mm) primary
      melanoma.
AB  - BACKGROUND: Thin melanomas have become increasingly prevalent, and lesions < or
      =1 mm in thickness are frequently diagnosed. They are considered highly curable
      when treated solely with wide local excision, with reported 5-year disease-free
      survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have
      increased potentials for metastasizing and late recurrences because of dermal
      lymphatics located at the interface of the papillary and reticular dermis. We
      have addressed this controversial area by reviewing the outcomes of patients with
      invasive thin melanomas. METHODS: We performed 266 sentinel lymph node biopsy
      procedures, using both radioisotope and blue dye, over a 5-year period. Sixty
      five of the 266 invasive melanomas were thin and were treated by wide local
      excision and sentinel lymph node biopsy. RESULTS: Two (3%) of the 65 thin
      melanomas were found to have a positive sentinel lymph node. In melanomas thinner
      than.75 mm, no positive sentinel lymph node was found. Therefore, only 3% of
      patients may benefit from tumor upstaging by sentinel lymph node biopsy.
      CONCLUSIONS: The occurrence of regional lymph node metastases in thin melanomas
      is rather low. Our data suggest that sentinel lymph node biopsy may not justified
      in patients with melanoma <.75 mm thick.

PMID- 12794025
TI  - Revised American Joint Committee on Cancer staging criteria accurately predict
      sentinel lymph node positivity in clinically node-negative melanoma patients.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) has recently modified
      staging criteria for primary melanoma patients and recommends sentinel lymph node
      (SLN) biopsy in many because microscopic nodal metastasis represents the most
      important factor predicting survival. The purpose of this study was to correlate
      the incidence of SLN metastasis with revised AJCC staging. METHODS: The records
      of 1375 melanoma patients undergoing SLN biopsy were reviewed. Univariate and
      multivariate analyses were performed to identify predictors of a positive SLN.
      Patients were stratified by using revised AJCC criteria to determine whether such
      groups also predicted positive SLNs. RESULTS: A positive SLN was found in 16.9%
      of patients. By multivariate analysis, tumor thickness (relative risk [RR], 3.4)
      and ulceration (RR, 2.2) were dominant independent predictors of SLN metastases;
      age < or =50 years (RR, 1.8) and axial tumor location (RR, 1.5) were also
      significant. When patients were stratified by AJCC staging criteria, a
      significant increase in SLN metastases between successive stages was
      demonstrated. CONCLUSIONS: Stratification of patients by using AJCC
      classification reveals an increasing risk of SLN metastases with successive stage
      groups. Given the significant association of SLN status and survival, the ability
      of the revised AJCC staging system to predict survival is likely due to its
      ability to predict the risk of occult nodal disease.

PMID- 12794024
TI  - Pentoxifyllin attenuates the systemic inflammatory response induced during
      isolated limb perfusion with recombinant human tumor necrosis factor-alpha and
      melphalan.
AB  - BACKGROUND: Isolated limb perfusion (ILP) with recombinant human tumor necrosis
      factor-alpha (rhTNF-alpha) and melphalan harbors the risk of septic shock-like
      syndrome. Pentoxifyllin (PTX) produced a beneficial effect on cytokine response
      and survival in animal experiments of septic shock, and we were interested to
      explore its effect during TNF-ILP in humans. METHODS: Eighteen consecutive
      patients underwent TNF-ILP and received PTX (30 mg/kg/day), whereas another 13
      consecutive patients did not. PTX was given systemically after the limb
      extracorporeal circulation was started. Cardiac index, systemic vascular
      resistance (SVR), and pulmonary vascular resistance were recorded via a Swan-Ganz
      catheter. Blood levels of TNF-alpha, interleukin-6, procalcitonin, and
      lipopolysaccharide-binding protein were determined before, during, and after ILP.
      RESULTS: After reperfusion, systemic levels of TNF-alpha were significantly less
      increased in the PTX group (peak, 2.8 vs. 1.3 ng/mL; P <.05), as were interleukin
      6 values (peak, 68 vs. 22 pg/mL; P <.02) and lipopolysaccharide-binding protein
      plasma levels (peak, 215 vs. 105 micro g/mL; P <.03). Differences in cardiac
      index, SVR, and mean arterial blood pressure were not significantly different.
      Norepinephrine or dobutamine to maintain SVR was less required in the PTX group.
      CONCLUSIONS: PTX attenuates systemic cytokine production and influences
      components of the systemic inflammatory response after TNF-ILP. PTX may play a
      beneficial role in the management of septic shock-like syndrome, particularly in
      patients with leakage from the ILP circuit.

PMID- 12794026
TI  - The amount of metastatic melanoma in a sentinel lymph node: does it have
      prognostic significance?
AB  - BACKGROUND: The amount of metastatic disease in the sentinel lymph node (SLN) is
      examined as a prognostic factor in malignant melanoma. METHODS: SLN mapping was
      performed on 592 patients with stage I and II malignant melanoma from March 1,
      1994, through December 31, 1999. One hundred four patients were found to have 134
      sentinel SLNs containing metastatic melanoma. The slides were reviewed, and the
      size of the metastatic melanoma in each SLN was measured. The size of the
      metastatic deposit was defined as macrometastasis (>2 mm), micrometastasis (< or
      =2 mm), a cluster of cells (10-30 grouped cells) in the subcapsular space or
      interfollicular zone, or isolated melanoma cells (1 to > or =20 individual cells)
      in subcapsular sinuses. RESULTS: The number of metastases in each SLN was
      isolated melanoma cells, n = 5 (3.7%); cluster of cells, n = 35 (26.1%); < or =2
      mm, n = 45 (33.6%); and >2 mm, n = 49 (36.7%). Seventy-nine patients (76%) had a
      single positive SLN. The size of the largest nodal metastasis was used to
      stratify patients with multiple positive SLNs. The overall 3-year survival for
      patients with SLN micrometastases was 90%, versus 58% for patients with SLN
      macrometastases (P =.004). CONCLUSIONS: The amount of metastatic melanoma in an
      SLN is an independent predictor of survival. Patients with SLN metastatic
      deposits >2 mm in diameter have significantly decreased survival.

PMID- 12794027
TI  - Platelet-derived endothelial cell growth factor mediates Rho-associated coiled
      coil domain kinase messenger RNA expression and promotes cell motility.
AB  - BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF), whose
      expression is increased in several cancers, is an endothelial cell mitogen and
      has chemotactic activity in vitro and angiogenic activity in vivo. Tumors with
      high PD-ECGF expression tend to have frequent lymph node metastasis and are
      associated with poor outcome. METHODS: We screened genes transduced by PD-ECGF
      transfection to the colon cancer cell line DLD-1 by using a complementary DNA
      microarray. Cell motility was evaluated by in vitro migration assay. Actin fiber
      polymerization was visualized by immunofluorescent detection of phalloidin.
      RESULTS: Rho-associated coiled-coil domain kinase (ROCK1) was found to be
      significantly overexpressed in PD-ECGF transfectants compared with mock cells. PD
      ECGF transfectants showed higher cell motility than mock cells. The parental
      cell, DLD-1, with recombinant PD-ECGF showed higher cell motility than that
      without recombinant PD-ECGF, in which motility was blocked by the neutralizing
      antibody of PD-ECGF or Y-27632, a specific inhibitor of ROCK1. Moreover, the
      actin fiber polymerization, which is a marker of activation of ROCK1, was higher
      in PD-ECGF transfectants than in mock cells. CONCLUSIONS: PD-ECGF expression may
      be associated with cancer cell migration via activation of ROCK1. This may
      explain one mechanism by which tumors with high expression of PD-ECGF show
      aggressive behavior.

PMID- 12794028
TI  - Heat acclimation increases skin vasodilation and sweating but not cardiac
      baroreflex responses in heat-stressed humans.
AB  - In the present study, to test the hypothesis that exercise-heat acclimation
      increases orthostatic tolerance via the improvement of cardiac baroreflex control
      in heated humans, we examined cardiac baroreflex and thermoregulatory responses,
      including cutaneous vasomotor and sudomotor responses, during whole body heating
      before and after a 6-day exercise-heat acclimation program [4 bouts of 20-min
      exercise at 50% peak rate of oxygen uptake separated by 10-min rest in the heat
      (36 degrees C; 50% relative humidity)]. Ten healthy young volunteers participated
      in the study. On the test days before and after the heat acclimation program,
      subjects underwent whole body heat stress produced by a hot water-perfused suit
      during supine rest for 45 min and 75 degrees head-up tilt (HUT) for 6 min. The
      sensitivity of the arterial baroreflex control of heart rate (HR) was calculated
      from the spontaneous changes in beat-to-beat arterial pressure and HR. The HUT
      induced a presyncopal sign in seven subjects in the preacclimation test and in
      six subjects in the postacclimation test, and the tilting time did not differ
      significantly between the pre- (241 +/- 33 s) and postacclimation (283 +/- 24 s)
      tests. Heat acclimation did not change the slope in the HR-esophageal temperature
      (Tes) relation and the cardiac baroreflex sensitivity during heating. Heat
      acclimation decreased (P < 0.05) the Tes thresholds for cutaneous vasodilation in
      the forearm and dorsal hand and for sweating in the forearm and chest. These
      findings suggest that short-term heat acclimation does not alter the spontaneous
      baroreflex control of HR during heat stress, although it induces adaptive change
      of the heat dissipation response in nonglabrous skin.

PMID- 12794029
TI  - Effect of puberty on coronary arteries from female pigs.
AB  - Vascular function changes following loss of ovarian hormones in women at
      menopause and in experimental animals following surgical ovariectomy. Little is
      known about changes in vascular function during hormonal transition from sexual
      immaturity (juvenile) to sexual maturity. Therefore, experiments were designed to
      determine effects of natural puberty on vascular function in female pigs. Tissue
      was studied from eight juvenile (2-3 mo) and eight adult (5-6 mo) female pigs.
      Plasma nitric oxide (NO) was measured, and mRNA for endothelium-derived NO
      synthase (eNOS) and eNOS protein were determined in aortic endothelial cells.
      Rings of coronary arteries were suspended for measurement of isometric force in
      organ chambers. Serum 17beta-estradiol levels were comparable in the two groups,
      whereas the arithmetic mean of progesterone levels was about two-thirds lower in
      adults compared with juvenile pigs. Plasma NO was significantly higher in
      juveniles compared with adults, but mRNA and protein for eNOS were comparable. In
      coronary arteries, an alpha2-adrenergic agonist caused greater endothelium
      dependent relaxations in rings from juvenile compared with adult pigs.
      Relaxations to bradykinin were similar in arteries from both groups, but
      inhibition of NO reduced relaxations only in arteries from juvenile pigs.
      Relaxations from NO were greater in arteries from adult compared with juvenile
      female pigs. In conclusion, coronary arterial endothelial and smooth muscle
      responses are selectively modulated at puberty in female pigs. At maturity,
      plasma NO is reduced and sensitivity of the smooth muscle to exogenous NO is
      increased. Posttranscriptional regulation of eNOS protein may explain differences
      in NO bioavailability in juvenile pigs.

PMID- 12794030
TI  - Changes in lung permeability and lung mechanics accompany homeostatic instability
      in senescent mice.
AB  - Aging and lung disease are recognized factors that increase mortality risk in
      subjects exposed to ambient particulate matter (PM). In an effort to understand
      the mechanisms of enhanced susceptibility, the present study examined an inbred
      mouse model of senescence to 1) determine changes in lung permeability as animals
      approach the end-of-life and 2) characterize age-dependent changes in lung
      mechanics in presenescent and terminally senescent mice. The clearance of
      technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to
      test the hypothesis that lung permeability increases with age and enhances uptake
      of soluble components of PM principally during the period several weeks before
      death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust
      and on terminally senescent AKR/J mice several weeks before death to assess the
      relative importance of lung mechanics. Abrupt body weight loss was used to signal
      imminent death because it accompanies indexes of physiological aging and terminal
      senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation
      was significantly (P < 0.05) enhanced in senescent mice. Age-dependent changes in
      lung mechanics were indicative of significant (P < 0.05) decrements in lung
      volume and compliance several weeks before death. Thus, during a period of
      homeostatic instability leading toward natural death, AKR/J mice showed enhanced
      permeability of soluble particles despite a decrease in lung volume and
      concomitant alveolar surface area. These results suggest that pulmonary
      epithelial-endothelial barrier dysfunction occurs in terminally senescent mice
      just before death. Furthermore, this senescent-dependent increase in lung
      permeability may be a contributing factor for increased PM susceptibility in the
      elderly and patients with lung disease.

PMID- 12794031
TI  - Compositional changes in lipid microdomains of air-blood barrier plasma membranes
      in pulmonary interstitial edema.
AB  - We evaluated in anesthetized rabbits the compositional changes of plasmalemmal
      lipid microdomains from lung tissue samples after inducing pulmonary interstitial
      edema (0.5 ml/kg for 3 h, leading to approximately 5% increase in extravascular
      water). Lipid microdomains (lipid rafts and caveolae) were present in the
      detergent-resistant fraction (DRF) obtained after discontinuous sucrose density
      gradient. DRF was enriched in caveolin-1, flotillin, aquaporin-1, GM1,
      cholesterol, sphingomyelin, and phosphatidylserine, and their contents
      significantly increased in interstitial edema. The higher DRF content in
      caveolin, flotillin, and aquaporin-1 and of the ganglioside GM1 suggests an
      increase both in caveolar domains and in lipid rafts, respectively. Compositional
      changes could be ascribed to endothelial and epithelial cells that provide most
      of plasma membrane surface area in the air-blood barrier. Alterations in lipid
      components in the plasma membrane may reflect rearrangement of floating lipid
      platforms within the membrane and/or lipid translocation from intracellular
      stores. Lipid traffic could be stimulated by the marked increase in hydraulic
      interstitial pressure after initial water accumulation, from approximately -10 to
      5 cmH2O, due to the low compliance of the pulmonary tissue, in particular in the
      basement membranes and in the interfibrillar substance. Compositional changes in
      lipid microdomains represent a sign of cellular activation and suggest the
      potential role of mechanotransduction in response to developing interstitial
      edema.

PMID- 12794032
TI  - Effect of contraction frequency on the contractile and noncontractile phases of
      muscle venous blood flow.
AB  - The purpose of this study was to test the hypothesis that increasing muscle
      contraction frequency, which alters the duty cycle and metabolic rate, would
      increase the contribution of the contractile phase to mean venous blood flow in
      isolated skeletal muscle during rhythmic contractions. Canine gastrocnemius
      muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic
      contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5
      contractions/s. The O2 uptake, tension-time integral, and mean venous blood flow
      increased significantly (P < 0.05) with each contraction frequency. Venous blood
      flow during both the contractile (106 +/- 6, 139 +/- 8, and 145 +/- 8 ml x 100 g
      1 x min-1) and noncontractile phases (64 +/- 3, 78 +/- 4, and 91 +/- 5 ml x 100 g
      1 x min-1) increased with contraction frequency. Although developed force and
      duration of the contractile phase were never significantly different for a single
      contraction during the three contraction frequencies, the amount of blood
      expelled from the muscle during an individual contraction increased significantly
      with contraction frequency (0.24 +/- 0.03, 0.32 +/- 0.02, and 0.36 +/- 0.03 ml x
      N-1 x min-1, respectively). This increased blood expulsion per contraction,
      coupled with the decreased time in the noncontractile phase as contraction
      frequency increased, resulted in the contractile phase contribution to mean
      venous blood flow becoming significantly greater (21 +/- 4, 30 +/- 4, and 38 +/-
      6%) as contraction frequency increased. These results demonstrate that the
      percent contribution of the muscle contractile phase to mean venous blood flow
      becomes significantly greater as contraction frequency (and thereby duty cycle
      and metabolic rate) increases and that this is in part due to increased blood
      expulsion per contraction.

PMID- 12794033
TI  - Endotoxemia and hepatic injury in a rodent model of hindlimb unloading.
AB  - Hindlimb unloading (HU) is known to induce physiological alterations in various
      organ systems that mimic some responses observed after exposure to microgravity.
      In the present study, the effects of up to 4 wk of HU on the liver were assessed
      in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and
      endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator
      of hepatic injury, were measured in portal and systemic blood samples. Endotoxin
      was elevated by approximately 50% in portal blood samples of mice and rats but
      was not detectable in systemic blood. This low-grade portal endotoxemia was
      associated with hepatic injury in rats and C57BL/6 mice as indicated by
      inflammation and elevated serum transaminase activities. Blood levels of the
      cytokine TNF-alpha were increased by approximately 50% in C57BL/6 mice; no
      significant elevation of this cytokine was detected in rats. Messenger RNA levels
      of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide
      binding protein were significantly enhanced after 3 wk of HU in endotoxin
      sensitive rodents. In contrast, no histological changes or significant increases
      in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal
      endotoxin levels of 222 +/- 83.4 pg/ml. At the 3-wk time point, expression of
      acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after
      4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these
      findings indicate that HU induced mild portal endotoxemia, which contributed to
      the observed hepatic injury in endotoxin-sensitive rodents.

PMID- 12794034
TI  - Responses to ozone are increased in obese mice.
AB  - Epidemiological data indicate an increased incidence of asthma in overweight
      adults and children. Ozone (O3) is a common trigger for asthma. Accordingly, the
      purpose of this study was to compare O3-induced airway hyperresponsiveness and
      airway inflammation in lean, wild-type (C57BL/6J) mice and mice that are obese as
      a consequence of a genetic defect in the gene encoding the satiety hormone leptin
      (ob/ob mice). The ob/ob mice eat excessively and weighed more than twice as much
      as age- and gender-matched wild-type mice. Airway responsiveness to intravenous
      methacholine was measured by forced oscillation. In air-exposed controls,
      baseline pulmonary resistance was greater, and the dose of methacholine required
      to double pulmonary resistance was lower in ob/ob than wild-type mice. Exposure
      to O3 (2 parts/million for 3 h) caused AHR and airway inflammation in both groups
      of mice, but responses to O3 were enhanced in ob/ob compared with wild-type mice.
      Administration of exogenous leptin did not reverse the enhanced inflammatory
      response observed in ob/ob mice, but augmented airway inflammation in wild-type
      mice. The inhaled dose of O3 per gram of lung tissue was greater in ob/ob than
      wild-type mice. Our results indicate that O3-induced airway responses are
      enhanced in ob/ob mice and suggest that inhaled O3 dose may be one factor
      contributing to this difference, but other aspects of the obese phenotype may
      also contribute. Our results also indicate that the hormone leptin, which is
      increased in the obese, has the capacity to increase airway inflammation.

PMID- 12794036
TI  - Chronic centrifugation (hypergravity) disrupts the circadian system of the rat.
AB  - The present study was conducted to evaluate the response of rat deep body
      temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute
      hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over
      three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized
      naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and 
      3.09 degrees C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was
      suppressed for the duration of centrifugation (vs. control period); the percent
      decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not
      significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, 
      63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation
      and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all
      circadian metrics except daily means. Periodicity analysis detected the
      phenomenon of circadian rhythm splitting, which has not been reported previously
      in response to chronic hypergravity exposure. Our analysis documents the
      disruptive and dose-dependent effects of hypergravity on circadian rhythmicity
      and the time course of adaptation to 14-day chronic centrifugation exposure.

PMID- 12794035
TI  - Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but
      not ventilation-perfusion matching.
AB  - After pneumonectomy (Pnx), mechanical strain on the remaining lung is an
      important signal for adaptation. To examine how mechanical lung strain alters gas
      exchange adaptation after Pnx, we replaced the right lung of adult dogs with a
      custom-shaped inflatable silicone prosthesis. The prosthesis was kept 1) inflated
      (Inf) to reduce mechanical strain of the remaining lung and maintain the
      mediastinum in the midline, or 2) deflated (Def) to allow lung strain and
      mediastinal shift. Gas exchange was studied 4-7 mo later at rest and during
      treadmill exercise by the multiple inert gas elimination technique while animals
      breathed 21 and 14% O2 in balanced order. In the Inf group compared with Def
      group during hypoxic exercise, arterial O2 saturation was lower and alveolar
      arterial O2 tension difference higher, whereas O2 diffusing capacity was lower at
      any given cardiac output. Dispersion of the perfusion distribution was similar
      between groups at rest and during exercise. Dispersion of the ventilation
      distribution was lower in the Inf group at rest, associated with a much higher
      respiratory rate, but rose to similar levels in both groups during hypoxic
      exercise. Mean pulmonary arterial pressure at a given cardiac output was higher
      in the Inf group, whereas peak cardiac output was similar between groups. Thus
      creating lung strain by post-Pnx mediastinal shift primarily enhances diffusive
      gas exchange with only minor effects on ventilation-perfusion matching,
      consistent with the generation of additional alveolar-capillary surfaces but not
      conducting airways and blood vessels.

PMID- 12794038
TI  - Preface. Neuroimmunomodulation: a Kuhnian model of evolution of a scientific
      field.

PMID- 12794037
TI  - Maximal intermittent cycling exercise: effects of recovery duration and gender.
AB  - This study aimed to evaluate potential gender differences in recovery of power
      output during repeated all-out cycling exercise. Twenty men and thirteen women
      performed four series of two sprints (Sp1 and Sp2) of 8 s, separated by 15-, 30-,
      60-, and 120-s recovery. Peak power (Ppeak), power at the 8th s, total mechanical
      work, and time to Ppeak were calculated for each sprint. Ppeak and mechanical
      work decreased significantly between Sp1 and Sp2 after 15-s recovery in both men
      (-6.4 and -9.4%, respectively) and women (-7.4 and -6.8%, respectively). Time to
      Ppeak did not change between recovery durations, but women reached their peak
      power more slowly than men (on average 5.15 +/- 1.2 and 3.8 +/- 1.2 s,
      respectively; P < 0.01). During Sp1 and Sp2, linear regressions from Ppeak to
      power at the 8th s showed a greater power decrease (%Ppeak) in women compared
      with men (P < 0.05). In conclusion, patterns of power output recovery between two
      consecutive short bouts were similar in men and women, despite lower overall
      performance and greater fatigability during sprints in women.

PMID- 12794039
TI  - Introduction. Neuroendocrine and neural factors in autoimmune, inflammatory,
      infectious, and allergic disease: a summary of the conference.

PMID- 12794041
TI  - Hippocampal interleukin-1 beta gene expression during long-term potentiation
      decays with age.

PMID- 12794042
TI  - Humoral links between sleep and the immune system: research issues.
AB  - In the last twenty years we have realized that the immune system synthesizes a
      class of peptides, termed cytokines, that play a central role in alerting the
      brain to ongoing inflammation in peripheral tissues. Among the brain's responses
      to proinflammatory cytokines, or agents that induce these cytokines, are certain
      alterations in sleep profiles. Characteristically there is an increase in non
      rapid eye movement sleep (NREMS), and NREMS intensity is often accompanied by a
      decrease in rapid eye movement sleep (REMS). Cytokines appear to play a role in
      normal sleep regulation; during pathology, higher levels of cytokines amplify the
      physiological cytokine sleep mechanisms. In this review we summarize the
      extensive literature on the roles of interleukin-1 (IL-1) and tumor necrosis
      factor-alpha (TNF-alpha) in sleep regulation, and their interactions with the
      neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing
      hormone (CRH). We reach the tentative conclusion that the sleep-promoting actions
      of IL-1 and GHRH are mediated via anterior hypothalamic neurons that are
      receptive to these substances. It also seems likely that TNF-alpha and CRH also
      influence these neurons. In addition, we discuss an array of research issues
      raised by these studies that remain to be resolved.

PMID- 12794043
TI  - HPA axis activation and neurochemical responses to bacterial translocation from
      the gastrointestinal tract.
AB  - Stress can cause migration of indigenous bacterial flora from the gut to the
      peritoneum, a phenomenon known as bacterial translocation. Destruction of the
      cell walls of gram-negative bacteria can result in the production of endotoxin
      (lipopolysaccharide, LPS), which is the likely cause of sepsis. Exogenously
      administered LPS can activate the hypothalamo-pituitary-adrenal (HPA) axis as
      well as brain noradrenergic and indoleaminergic systems. Thus, it is possible
      that activations of these systems associated with laboratory stressors in rats
      and mice could be attributed to bacterial translocation and LPS production. To
      test this hypothesis we conducted experiments on the time course of bacterial
      translocation in response to restraint in mice, while measuring HPA and
      neurochemical responses. These experiments failed to show good correlations
      between the occurrence of bacterial translocation and HPA and neurochemical
      activations, suggesting that the later responses were not linked to bacterial
      translocation. This conclusion was supported by the observation of normal
      neurochemical responses to restraint in germ-free mice. In further experiments,
      translocation of Salmonella typhimurium, a bacterium that readily translocates in
      unstressed animals, was associated with HPA activation and noradrenergic and
      indoleaminergic responses, indicating that bacterial translocation can indeed
      activate the HPA axis and brain amines. However, the above experiments suggest
      that this is not the mechanism by which restraint activates these systems.

PMID- 12794044
TI  - Pathophysiology of cerebral malaria: role of host cells in the modulation of
      cytoadhesion.
AB  - Cerebral malaria (CM), one of the most serious complications of Plasmodium
      falciparum infection, is characterized by the sequestration of infected
      erythrocytes (IEs) in cerebral microvascular beds. The precise mechanisms
      involved in the onset of neuropathology remain unknown, but parasite
      sequestration in the brain, metabolic disturbances, and host immune responses all
      play a role. Studies in a murine model of CM showed a potential role for host
      cells, especially platelets, in the pathogenesis of CM. Indeed, urokinase
      plasminogen activator receptor (uPAR; CD87) deficiency attenuates the severity of
      CM, most likely by its important role in platelet kinetics and trapping. These
      results led us to evaluate whether platelets have a role in the human disease. By
      immunostaining of brain samples from Malawian patients, we determined that the
      surface of platelet accumulation and the proportion of vessels filled with
      platelets were significantly higher in patients who died of CM than in those who
      died of other causes. We then investigated the role of platelets in IE
      cytoadhesion in vitro, using CD36-binding IE (IECD36) and CD36-deficient
      (CD36DEF) brain microvascular endothelial cells (ECs). Coincubation studies
      indicated that platelets can induce strong IECD36 binding to CD36DEF ECs and,
      conversely, can hide constitutively expressed falciparum receptors such as
      chondroitin sulfate A. Thus, platelets may provide an adhesion receptor to
      microvascular beds originally devoid of it. This novel mechanism of cytoadhesion
      may reorient the sequestration of different parasite phenotypes and play an
      important role in the pathogenesis of severe malaria.

PMID- 12794045
TI  - Interleukin-1 in the brain: mechanisms of action in acute neurodegeneration.
AB  - Interleukin-1 (IL-1) exerts a number of diverse actions in the brain, and it is
      currently well accepted that it contributes to experimentally induced
      neurodegeneration. Much of this is based on studies using the IL-1 receptor
      antagonist, which inhibits cell death caused by ischemia, brain injury, or
      excitotoxins. Our aim is to determine how and where in the brain IL-1 acts to
      produce these effects. Most of the neurodegenerative effects of IL-1 are thought
      to be through IL-1 beta. However, we have data implicating IL-1 alpha in
      excitotoxic cell death. Furthermore mice lacking both IL-1 alpha and IL-1 beta
      show dramatically reduced ischemic cell death, whereas deletion of IL-1 alpha or
      IL-1 beta alone fails to modify damage. It has also been demonstrated that IL-1
      exacerbates ischemic injury in mice in the absence of the type I IL-1 receptor,
      suggesting the existence of novel IL-1 receptors in the brain. IL-1 also
      dramatically exacerbates neuronal loss in response to intrastriatal
      administration of the excitotoxin AMPA in the rat brain, an effect accompanied by
      marked increases in cytokine expression in the frontoparietal cortex, which
      precedes subsequent cell death in this region. Intrastriatal AMPA also results in
      limbic seizures that are exacerbated by IL-1, and we hypothesize, therefore, that
      IL-1 exacerbates cell death through increased seizure activity. Therefore, IL-1
      appears to induce acute neurodegeneration through a number of mechanisms.

PMID- 12794046
TI  - Antibodies to neuronal targets in neurological and psychiatric diseases.
AB  - The role of antibodies to specific neuronal and muscle ion channels in the
      etiology of neuromuscular transmission disorders is now well accepted. In
      addition, maternal antibodies can cross the placenta and cause neonatal disease
      or even alter the development of the infant, raising the possibility that some
      neurodevelopmental conditions could be caused by maternal antibodies. Voltage
      gated ion channels are expressed in the brain as well as at the neuromuscular
      junction, and in recent years it has become clear that antibodies to some central
      nervous system (CNS) channels can be associated with CNS disease. This review
      highlights features of these conditions, preliminary investigations into
      neurodevelopmental disorders, and areas for further study.

PMID- 12794047
TI  - Activation of complement in the central nervous system: roles in
      neurodegeneration and neuroprotection.
AB  - The complement system is an essential effector of the humoral and cellular
      immunity involved in cytolysis and immune/inflammatory responses. Complement
      participates in host defense against pathogens by triggering the formation of the
      membrane attack complex. Complement opsonins (C1q, C3b, and iC3b) interact with
      surface complement receptors to promote phagocytosis, whereas complement
      anaphylatoxins C3a and C5a initiate local inflammatory responses that ultimately
      contribute to the protection and healing of the host. However, activation of
      complement to an inappropriate extent has been proposed to promote tissue injury.
      There is now compelling evidence that complement activation in the brain is a
      double-edged sword in that it can exert beneficial or detrimental effects
      depending on the pathophysiological context. This review focuses on the roles of
      the complement system in the pathogenesis of acute brain injury (cerebral
      ischemia and trauma) and chronic neurodegeneration (Alzheimer's disease). Because
      many effects of the complement appear to promote neuronal survival and tissue
      remodeling, directing activation of the complement system in the brain may
      provide a better therapeutic rationale than inhibiting it.

PMID- 12794048
TI  - Role of nitric oxide in regulating the rat hypothalamic-pituitary-adrenal axis
      response to endotoxemia.
AB  - This work examines the role of nitric oxide (NO) in the periphery (i.e., on the
      pituitary) and the brain (particularly on corticotropin-releasing factor [CRF]
      and vasopressin [VP] neurons in the paraventricular nucleus [PVN] of the
      hypothalamus) as a modulator of the ACTH response to lipopolysaccharide. We
      previously showed that NO restricted the pituitary response to VP while it
      facilitated the synthesis of PVN CRF and VP. In our experience, only relatively
      high doses of lipopolysaccharide (>50 microg/kg, injected intravenously [i.v.])
      cause detectable increases in PVN neuronal activation. Our hypothesis, therefore,
      was that pituitary NO-VP interactions would predominate in rats injected with a
      low dose of lipopolysaccharide (0.5 microg/kg, i.v.) while the stimulatory
      influence of the gas on PVN neuronal activity would play an important role
      following i.v. injection of a large dose of lipopolysaccharide (50 microg/kg,
      i.v.). We observed that the ability of 0.5 microg/kg lipopolysaccharide to
      release ACTH was significantly enhanced by the subcutaneous (s.c.), but not the
      intracerebroventricular (i.c.v.) injection of L-NAME, an arginine derivative that
      blocks NO synthesis. The effect of s.c. L-NAME was reversed by
      immunoneutralization of endogenous VP, which indicated that in this model, the
      ability of lipopolysaccharide to release ACTH depended, at least in part, on the
      influence exerted by NO on the pituitary response to VP. In rats injected with
      the high lipopolysaccharide dose, the s.c. injection of L-NAME decreased plasma
      ACTH levels compared to those in rats pretreated with the vehicle. The effect of
      s.c. L-NAME was not significantly altered by VP antibodies. These results
      indicate that in this model, the primary influence of NO was exerted in the PVN
      and/or its afferents and that it did not depend on a peripheral, VP-mediated
      effect of the gas. On the one hand, these data are at odds with our finding that
      the i.c.v. injection of L-NAME only marginally altered the ACTH response to the
      large dose of lipopolysaccharide. As i.c.v. injected L-NAME should have primarily
      decreased hypothalamic, but not pituitary NOS, its only modest influence on ACTH
      release may have been due to a balance between stimulating and inhibiting effects
      of NO within the brain. As high doses of lipopolysaccharide increase brain levels
      of prostaglandin, monoamine, and proinflammatory cytokines, it will be important
      to investigate the influence exerted by NO on these secretagogues and on their
      interactions with PVN CRF and VP neurons, which may help us resolve the issues
      raised by our results. Collectively, these data support our hypothesis that the
      mechanisms mediating the ACTH response to a low lipopolysaccharide concentration
      involve the inhibitory VP-mediated influence of NO on pituitary activity. By
      contrast, the stimulatory effect of high doses of lipopolysaccharide on ACTH
      release depends, at least in part, on the ability of NO to upregulate PVN
      neuronal activity.

PMID- 12794049
TI  - Effect of neurogenic stress and ethanol on nitric oxide synthase and
      cyclooxygenase activities in rat adrenals.
AB  - Repeated restraint stress (RRS) in male rats activated the pituitary adrenal
      system, as indicated by increases in adrenal weight and plasma corticosterone
      concentration that were accompanied by a decrease in constitutive nitric oxide
      synthase (cNOS), but not inducible NOS (iNOS). iNOS activated cyclooxgenase,
      causing elevated prostaglandin E(2) (PGE(2)) and F(2 alpha) in the adrenals, but
      had no effect on lipoxygenase. Administration of ethanol (ETOH) was also
      associated with elevated adrenal weight and a slight increase in corticosterone
      coupled with a decrease in both cNOS and iNOS and PGs in the adrenal. When ETOH
      was administered together with RRS, a decrease in iNOS and PGE release was noted
      consequent to a reduction in iNOS. Thus, ETOH probably reduced RRS-induced
      adrenocorticotropic hormone release. Adrenals were incubated in vitro to further
      evaluate the role of NO in these processes. Results indicated that NO released by
      sodium nitroprusside increased corticosterone release presumably by activating
      guanylyl cyclase with production of cyclic guanosine monophosphate (cGMP),
      because although NO also increased PGE release, PGE(2) (10(-5)-10(-9) M)
      decreased corticosterone release, an effect that was highly significant at a
      concentration of 10(-7) M PGE(2). ETOH (100 mM) had no effect on corticosterone
      release and did not block the increase in corticosterone caused by NO; however,
      ETOH reduced PGE release into the medium and blocked PGE(2) release induced by
      NO. Consequently, NO activated corticosterone release not by PGs, but by
      activation of guanylyl cyclase and release of cGMP. PGs have a negative feedback
      to suppress corticosterone release.

PMID- 12794050
TI  - Hypothalamo-pituitary-adrenal axis and chronic immune activation.
AB  - Corticosteroids have potent immunosuppressive and anti-inflammatory effects.
      Although corticosteroids are an important weapon in the clinical arsenal for
      treating inflammatory episodes, the mechanisms underlying the actions and
      regulation of endogenous corticosteroids remain obscure. In the late 1980s and
      early 1990s, a hypothesis was proposed that suggested that susceptibility to
      autoimmune disease was linked to a hypoactive hypothalamo-pituitary-adrenal (HPA)
      axis. It was further suggested that this defect in regulation of the HPA axis was
      situated at the level of the hypothalamus. This compelling hypothesis directly
      linked control of the HPA axis with susceptibility to disease rather than just
      severity of inflammation. The initial findings acted as a stimulus to further
      research, and over the next decade the hypothesis was tested. Recent studies
      suggest that the original hypothesis is in need of modification and that
      susceptibility is more complex and requires the involvement of more than a single
      parameter. These data are discussed together with recent developments concerning
      regulation of the HPA in disease in preclinical models and patients with
      rheumatoid arthritis. The latter studies in patients with rheumatoid arthritis
      provide evidence for the existence of a subpopulation of these patients with
      altered negative feedback regulation of the HPA axis.

PMID- 12794051
TI  - Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) as well as most autoimmune disorders results from a
      combination of several predisposing factors including the relations between
      epitopes of the trigger agent (i.e., virus, self-antigens) and histocompatibility
      epitopes (i.e., HLA), the status of the stress response system including the
      hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic nervous
      system (SNS), as well as the gonadal hormones (hypothalamic-pituitary-gonadal
      axis, HPG), with estrogens implicated as enhancers of the immune response and
      androgens and progesterone as natural suppressors. The regular observation of
      reduced cortisol and adrenal androgen secretion during testing in RA patients not
      treated with glucocorticoids should clearly be regarded as "relative adrenal
      insufficiency" in the setting of a sustained inflammatory process, as shown by
      high interleukin (IL)-6 levels. In polymyalgia rheumatica, several pathogenetic
      and clinical aspects of the disease might well overlap RA, at least with elderly
      onset RA (EORA). Therefore, reduced production of adrenal hormones (i.e.,
      cortisol, DHEAS) at baseline in active and untreated patients with polymyalgia
      rheumatica was detected. The defect was mainly related to altered adrenal
      responsiveness to ACTH stimulation (i.e., increased 17-OHP), at least in
      untreated patients with polymyalgia rheumatica. Finally, normal serum estrogen
      and low androgen levels, but high synovial fluid estrogen and much lower androgen
      levels, have been found in RA patients, supporting the fundamental role of the
      peripheral sex hormone metabolism in the manifestations of the disease.

PMID- 12794052
TI  - The hypothalamo-pituitary-adrenal axis in multiple sclerosis.
AB  - During multiple sclerosis (MS), an inflammatory demyelinating disease of the
      central nervous system (CNS), activation of the hypothalamo-pituitary-adrenal
      (HPA) axis is considered to modulate the immune system in such a way that the
      probability of recovery from a relapse is increased. In a series of postmortem
      studies we observed a significant activation of corticotropin releasing hormone
      (CRH) neurons and increased cortisol in the cerebrospinal fluid (CSF) of MS
      patients, indicating activation of the HPA axis in this disease. On the other
      hand, sepsis, while elevating cortisol in control subjects, did not associate
      with a further increase of cortisol in MS patients. Thus, the activated HPA
      system in MS does not respond to an acute inflammatory stimulus. In order to
      investigate the role of chronic inflammation in the CNS in the activation of the
      HPA axis in MS, MS lesions in the hypothalamus were quantified and interleukin
      (IL)-6 levels in the CSF were determined. There was no difference in IL-6 levels
      between MS and control patients. A positive correlation was found between
      cortisol and IL-6 in control subjects with sepsis, but not in MS patients with
      sepsis or MS and control groups without sepsis. Thus, IL-6 in the CSF of MS
      patients is not the cause of the activation of the HPA system in MS. We found a
      remarkably high incidence (95% of the patients) of MS lesions in the
      hypothalamus, of which the majority (60%) were active. The more active lesions
      were present in the hypothalamus, the shorter the disease duration to the moment
      of death, indicative of a worse disease course. Preliminary data show suppression
      of the activation of CRH neurons by active hypothalamic MS lesions. We propose
      that this suppression of CRH neurons by active hypothalamic MS lesions causes the
      concomitant unfavorable disease course via an inadequate cortisol response during
      relapses of MS.

PMID- 12794053
TI  - Effects of in vitro and in vivo opioids on the production of IL-12 and IL-10 by
      murine macrophages.
AB  - We evaluated the ability of the specific micro opioid receptor agonist DAMGO, the
      kappa-specific agonist U-50488 in vitro, and exogenous opioid morphine
      administered in vivo both acutely and chronically to modulate IL-12 and IL-10
      production by murine peritoneal macrophages. Damgo and U-50488 at the
      concentrations of 10(-6) and 10(-8) M decreased the production of IL-12 without
      affecting IL-10. One hour after the acute administration of 5, 10, and 20 mg/kg
      of morphine a dose-related decrease of both IL-10 and IL-12 levels was present.
      The pretreatment with naltrexone at doses up to 20 mg/kg did not prevent the
      decrease of IL-10 and IL-12 induced by morphine. When the drug was administered
      chronically, a differential development of tolerance to the immune effects was
      observed. After 3 days of treatment the effect of the acute challenge with 20
      mg/kg of morphine on IL-12 was lost. In contrast, morphine-induced inhibition of
      IL-10 disappeared between 10 and 12 days of treatment, in parallel with tolerance
      to the antinociceptive effect. These results suggest that opioids modulate
      macrophage cytokine production. However, the effects exerted by the in vivo
      administration of morphine are not superimposable onto those induced by the in
      vitro administration of specific opioid agonists.

PMID- 12794054
TI  - PACAP in immunity and inflammation.
AB  - The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide
      belonging to the VIP/secretin/glucagon family of peptides, produced by the
      lymphoid cells, which exerts a wide spectrum of immunological functions
      controlling the homeostasis of immune system through different receptors
      expressed in various immunocompetent cells. In the last decade, PACAP has been
      clearly identified as a potent anti-inflammatory factor that exerts its function
      by regulating the production of both anti- and proinflammatory mediators. In this
      sense, PACAP prevents death by septic shock, an acute inflammatory disease with a
      high mortality. In addition, PACAP regulates the expression of costimulatory
      molecules, inasmuch as this related to the modulation in the shift from Th1
      towards Th2 differentiation. We recently reported that PACAP prevents the
      deleterious effects of arthritis by downregulating both inflammatory and
      autoimmune components of the disease. Therefore, PACAP and analogs have been
      proposed as very promising candidates, alternative to other existing treatments,
      for treating acute and chronic inflammatory and autoimmune diseases, such as
      septic shock, arthritis, multiple sclerosis, Crohn's disease, or autoimmune
      diabetes.

PMID- 12794055
TI  - Sympathetic abnormalities during autoimmune processes: potential relevance of
      noradrenaline-induced apoptosis.
AB  - The sympathetic nervous system is one of the major pathways involved in immune
      neuroendocrine interactions. Disturbances in these interactions are likely to
      have consequences during lymphoproliferative diseases. Work derived from our
      group as well as from several others led us to the hypothesis that the
      overstimulation of the immune system that characterizes this type of pathology
      results in decreased sympathetic nerve activity in lymphoid organs. To explore
      this possibility, we used as a model lpr/lpr mice, which develop a genetically
      determined autoimmune, lupus-like lymphoproliferative disease. We show that 18
      week-old female C57Bl/6J lpr/lpr mice, which do not show overt symptoms of the
      disease but already have increased IgM and IgG2a levels in the blood, have
      decreased noradrenaline (NA) concentration and content in the spleen, but not in
      the kidney, as compared to normal C57Bl/6J littermates. Lpr/lpr mice do not
      express normal Fas, and therefore apoptosis cannot be triggered through this
      receptor. The defects in sympathetic innervation in the spleen of lpr/lpr mice
      prompted us to evaluate whether NA could influence lymphoid cell mass by inducing
      apoptosis. We found that NA can directly induce apoptosis in normal lymphoid
      cells via beta-adrenergic receptors. From the reported results we propose that
      reduction in sympathetic nerve function in lpr/lpr mice contributes to
      aggravation of the disease and suggest that in addition to the incapacity to
      mount Fas-mediated apoptosis, a second proapoptotic mechanism, namely, that
      triggered by NA, is defective in these animals because of reduced availability of
      the neurotransmitter.

PMID- 12794056
TI  - Antimicrobial chromogranins and proenkephalin-A-derived peptides: Antibacterial
      and antifungal activities of chromogranins and proenkephalin-A-derived peptides.
AB  - The secretory granules from adrenal medullary chromaffin cells contain a complex
      mixture of low-molecular mass constituents such as catecholamines, ascorbate,
      nucleotides, calcium, peptides, and several high-molecular mass water-soluble
      proteins including chromogranins and proenkephalin-A. These proteins are
      sequestered into secretory granules in which processing yields a large variety of
      peptides. These fragments are released into the extracellular space upon cell
      stimulation and are recovered in blood, lymph, cerebrospinal fluid, and synovial
      fluid. Some of them have biological activity on cells in an autocrine, paracrine,
      or endocrine fashion. In addition, we have shown that peptides with antimicrobial
      activity are present with the secretory chromaffin granules and demonstrated that
      they are released from stimulated chromaffin cells. We have shown that
      posttranslational modifications modulate the antimicrobial activities. For some
      peptides, using confocal laser microscopy, we have examined the interaction of
      the rhodaminated peptides with biological membranes. In addition, we have shown
      that chromofungin, the antifungal peptide corresponding to chromogranin A(47-66),
      can bind calmodulin in the presence of calcium and induce inhibition of
      calcineurin, a calmodulin-dependent enzyme. Because these antibacterial peptides
      are colocalized with catecholamines, they may be activated during stress, playing
      a role as a first protective barrier against bacterial infection, and thus act as
      factors of the innate immunity shortly after infection and before the induction
      and mobilization of an adaptative immune system.

PMID- 12794057
TI  - In vivo effects of growth hormone on thymic cells.
AB  - Increasing evidence has placed the thymus as a target for neuroendocrine control.
      Herein we review the pleiotropic effects of growth hormone (GH) on this primary
      lymphoid organ, with emphasis on data derived from in vivo experiments. A series
      of results strongly indicate that GH enhances thymocyte proliferation in both
      rodents and humans. Moreover, in vivo treatment with GH enhances interleukin (IL)
      6 production by mouse thymocytes, and ex vivo experiments show that production of
      other cytokines, such as IL-1 and GM-CSF, is also augmented. In a second vein, GH
      exerts a modulatory role on thymic hormone production, particularly the secretion
      of thymulin. In GH-treated animals as well as GH-transgenic mice, thymulin
      secretion is enhanced. In acromegalic patients we found higher levels of thymulin
      secretion, whereas the opposite was seen in dwarf mice and GH receptor knockout
      animals. Developing T cell migration is also under GH influence. Recombinant GH
      was found to increase human T cell engraftment in the thymus of SCID mice.
      Moreover, ex vivo thymocyte traffic into and out of thymic nurse cell complexes
      is enhanced after GH treatment. Lastly, we show that thymocyte export in vivo is
      modulated by GH, which favors the homing of CD4(+) recent thymic emigrants
      towards lymph nodes. In conclusion, the possibility that GH improves in vivo
      thymic functions, including thymocyte proliferation and migration, points to this
      molecule as a potential therapeutic adjuvant in T cell associated
      immunodeficiencies.

PMID- 12794058
TI  - Role of the thymus in the development of tolerance and autoimmunity towards the
      neuroendocrine system.
AB  - The thymus is the unique lymphoid organ inside which a confrontation occurs
      throughout life between neuroendocrine self-antigens and a recently evolved
      system with original recombination machinery driving random generation of immune
      response diversity. Through transcription of neuroendocrine genes in the thymus
      stromal network and expression of cognate receptors by immature T cells, the
      neuroendocrine system regulates early T cell differentiation. In addition and
      more specifically, intrathymic presentation of neuroendocrine self-antigens by,
      or in close association with, major histocompatibility complex (MHC) proteins is
      responsible for the establishment of central immune self-tolerance of
      neuroendocrine principles. All members of the insulin gene (INS) family are
      expressed in the thymus stroma according to a precise hierarchy and cell
      topography: IGF2 (thymic epithelial cells) > IGF1 (thymic macrophages) >> INS
      (thymic medullary epithelial cells and/or dendritic cells). Given this
      hierarchical pattern in gene expression, the protein IGF-2 is more tolerated than
      INS. Igf2 transcription is defective in the thymus of bio-breeding (BB) rat, one
      animal model of type 1 diabetes (T1DM). This thymus-specific defect in Igf2
      expression may explain both the absence of central tolerance to INS-secreting
      beta cells and the lymphopenia (including lack of regulatory RT6(+) T cells) in
      diabetes-prone BB rats. INS B:9-23 and the homologous sequence of IGF-2 compete
      for binding to DQ8, an MHC class II allele conferring major susceptibility to
      T1DM. In young DQ8(+) T1DM patients, INS B:9-23 presentation by DQ8 elicits a
      dominant IFN-gamma secretion by isolated PBMCs, whereas presentation of the IGF-2
      self-antigen promotes a dominant regulatory interleukin-10 secretion. These data
      demonstrate that opposite immune responses are driven by MHC presentation of a
      self-antigen (here, IGF-2) and an autoantigen (INS, as "altered" self). The
      important tolerogenic properties of thymic self-antigens deserve now to be
      exploited for prevention and/or cure of devastating autoimmune diseases such as
      T1DM.

PMID- 12794059
TI  - Integrating systemic information at the molecular level: cross-talk between
      steroid receptors and cytokine signaling on different target cells.
AB  - An essential event in immune activation is the increase of cytokines in both
      plasma and immune tissues. Steroid hormones influence several adaptive responses
      in both health and disease. Cytokines and steroids have an intimate cross
      communication in many systems, making possible a satisfactory adaptive response
      to environmental changes. The ultimate level of integration of the cytokine
      steroids cross-talk is the molecular level. We have demonstrated this in four
      types of cross-talk mechanisms on different cells in which steroids have major
      roles: (1) The tumor necrosis factor (TNF)-glucocorticoid receptor (GR)
      transcriptional interaction in cellular targets of TNF-induced cytotoxicity. TNF
      potentiates the transactivation activity of GR and the priming with TNF increases
      the protective action of GR on TNF-induced cytotoxicity. (2) The GR-T cell
      receptor (TCR) antagonism in GR-TCR-induced T cell apoptosis and its modulation
      by cAMP. cAMP inhibits the TCR-induced apoptosis through a PKA-CREB-dependent
      mechanism and potentiates glucocorticoid-induced apoptosis by means of a CREB
      independent mechanism. (3) The GR influence on Th1-Th2 cytokine expression and
      differentiation. Glucocorticoids inhibit the induction of GATA-3 and T-bet
      transcription factors. (4) The influence of ER/Smad-4 signaling cross
      communication on prolactinoma pathogenesis. Physical and functional interactions
      between Smad-4 and estrogen receptors take place in prolactinoma cells, providing
      a molecular explanation to link the tumorigenic action of these two important
      players of prolactinoma pathogenesis. The molecular cross-talk between steroids
      and transcription factors is the mechanism that provides the basis for the
      outcome of adaptive responses integrating the systemic information provided by
      hormones and cytokines.

PMID- 12794060
TI  - Stress, leukocyte trafficking, and the augmentation of skin immune function.
AB  - Delayed type hypersensitivity (DTH) reactions represent cell-mediated immune
      responses that exert important immunoprotective (resistance to viruses, bacteria,
      and fungi) or immunopathologic (allergic or autoimmune hypersensitivity) effects.
      We have used the skin DTH response as an in vivo model to study neuro-endocrine
      immune interactions. We hypothesized that just as an acute stress response
      prepares the cardiovascular and musculoskeletal systems for fight or flight, it
      may also prepare the immune system for challenges (e.g., wounding) that may be
      imposed by a stressor (e.g., an aggressor). Studies showed that acute (2 hours)
      stress experienced before primary or secondary cutaneous antigen exposure induces
      significantly enhanced skin DTH. This enhancement involves innate as well as
      adaptive immune mechanisms. Adrenalectomy eliminates the stress-induced
      enhancement of DTH. Acute administration of physiological concentrations of
      corticosterone and/or epinephrine to adrenalectomized animals enhances skin DTH.
      Compared with those in controls, DTH sites from acutely stressed or hormone
      injected animals show significantly greater erythema and induration, numbers of
      infiltrating leukocytes, and levels of cytokine gene expression. In contrast to
      acute stress, chronic stress is immunosuppressive. Chronic exposure to
      corticosterone or acute exposure to dexamethasone significantly suppresses skin
      DTH. These results suggest that during acute stress, endogenous stress hormones
      enhance skin immunity by increasing leukocyte trafficking and cytokine gene
      expression at the site of antigen entry. Elucidation of mechanisms mediating a
      stress-induced enhancement of skin immune function is important because such
      immunoenhancement can have protective (wound healing, resistance to infection) or
      pathological (allergic or autoimmune hypersensitivity) consequences.

PMID- 12794061
TI  - The role of neural inflammation in asthma and chronic obstructive pulmonary
      disease.
AB  - The tachykinins substance P and neurokinin A are found within airway nerves and
      immune cells. They have various effects on the airways that can contribute to the
      changes observed in asthma and chronic obstructive pulmonary disease. Both
      tachykinin NK(1) and NK(2) receptors have been involved in the
      bronchoconstriction and the proinflammatory changes induced by substance P and
      neurokinin A. Tachykinin NK(1) and NK(2) receptor antagonists have activity in
      various animal models of allergic asthma and chronic bronchitis. It is suggested
      that dual NK(1)/NK(2) and triple NK(1)/NK(2)/NK(3) tachykinin receptor
      antagonists have potential in the treatment of obstructive airway diseases.

PMID- 12794062
TI  - Endocrine and immune responses to stress in chronic inflammatory skin disorders.
AB  - Atopy is a genetically and environmentally determined condition predisposing to
      different forms such as atopic dermatitis (AD) or allergic asthma (AA). Both AD
      and AA are considered to be multifactorial diseases; however, distinct
      immunologic abnormalities have been described that play a crucial role. There is
      growing evidence that immunoglobulin-E hypersecretion and activation of the
      predominantly T-helper-2 (TH2)-like T cell subset trigger allergic inflammatory
      processes and cause the disease to become chronic. In the present paper, data
      suggesting reduced hypothalamic-pituitary-adrenal (HPA) axis responsiveness in
      patients with AD and AA are summarized, and the potential etiologic significance
      of a hyporeactive HPA axis is discussed. We propose that because of defective HPA
      axis, immunoregulation under stressful conditions is ineffective in patients with
      atopic conditions, leading to aberrant immune responses and subsequent
      exacerbation of the disease. Further research into the role of the HPA axis in
      atopy may elucidate the cause of stress-induced exacerbation of atopic symptoms
      and may be of clinical relevance.

PMID- 12794063
TI  - Neurotrophins in allergic airway dysfunction: what the mouse model is teaching
      us.
AB  - Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic
      factor (BDNF) are potent mediators of neuronal plasticity in the adult. There is
      increasing evidence that they regulate a variety of immune functions as well.
      Thus, neurotrophins are candidate molecules for neuroimmune interactions in
      allergic bronchial asthma, where elevated neurotrophin levels have been reported.
      In a mouse model of allergic airway inflammation we have identified macrophages
      and lymphocytes as additional cellular sources of NGF and BDNF in the inflamed
      lung. There was an unusual time course of BDNF in bronchoalveolar lavage fluid.
      BDNF levels peaked 1 week after the last allergen challenge, and did not
      correlate with the time course of the inflammatory response. In a series of
      experiments using blocking anti-NGF and anti-BDNF antibodies, we have shown that
      NGF specifically enhances inflammation and the allergic early-phase response. In
      contrast, BDNF influenced chronic airway obstruction and local neuronal
      hyperreactivity without affecting inflammation. Using transgenic mice
      overexpressing NGF in the airway epithelium, we have confirmed the data obtained
      from anti-NGF experiments. Allergen-challenged NGF overexpressors displayed a
      markedly augmented airway inflammation, early-phase response, and sensory
      irritation compared to wild-type mice. Studies with p75-NTR (-/-) knockout mice
      showed that these NGF effects are at least in part mediated by the low-affinity
      neurotrophin receptor. Thus, our experiments suggest that NGF and BDNF have a
      profound, but differential impact on allergic airway dysfunction.

PMID- 12794064
TI  - POLN, a nuclear PolA family DNA polymerase homologous to the DNA cross-link
      sensitivity protein Mus308.
AB  - The Drosophila Mus308 gene is unusual in encoding both a family A DNA polymerase
      domain and a DNA/RNA helicase domain. A mus308 mutation was shown to result in
      increased sensitivity to DNA cross-linking agents, leading to the hypothesis that
      Mus308 functions in the repair of DNA interstrand cross-links. Recently a
      mammalian ortholog of Mus308, POLQ, has been identified. We report here the
      identification, cloning, and characterization of POLN and its gene product, a new
      mammalian DNA polymerase also related to Mus308. The human cDNA encodes a protein
      of 900 amino acid residues. The region starting from residue 419 shares 33%
      identity (48% similarity) with the equivalent region of Escherichia coli DNA
      polymerase I. POLN is expressed in human cell lines with numerous alternatively
      spliced transcripts, and a full-length human coding region that comprises 24
      exons within 160 kilobases of genomic DNA. Expression analysis by northern
      blotting and in situ hybridization showed highest expression of full-length POLN
      in human and mouse testis. POLN localized to the nucleus when expressed as a
      enhanced green fluorescent protein (GFP)-tagged protein in human fibroblasts. GFP
      tagged recombinant POLN had DNA polymerase activity on activated calf thymus DNA
      and on a singly primed template.

PMID- 12794065
TI  - The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity.
AB  - The human Dnmt2 protein is one member of a protein family conserved from
      Schizosaccharomyces pombe and Drosophila melanogaster to Mus musculus and Homo
      sapiens. It contains all of the amino acid motifs characteristic for DNA
      (Cytosine-C5) methyltransferases, and its structure is very similar to
      prokaryotic DNA methyltransferases. Nevertheless, so far all attempts to detect
      catalytic activity of this protein have failed. We show here by two independent
      assay systems that the purified Dnmt2 protein has weak DNA methyltransferase
      activity. Methylation was observed at CG sites in a loose ttnCGga(g/a) consensus
      sequence, suggesting that Dnmt2 has a more specialized role than other mammalian
      DNA methyltransferases.

PMID- 12794066
TI  - Roles of low specificity and cofactor interaction sites on thrombin during factor
      XIII activation. Competition for cofactor sites on thrombin determines its fate.
AB  - Factor XIII is activated by thrombin, and this reaction is enhanced by the
      presence of fibrin(ogen). Using a substrate-based screening assay for factor XIII
      activity complemented by kinetic analysis of activation peptide cleavage, we show
      by using thrombin mutants of surface-exposed residues that Arg-178, Arg-180, Asp
      183, Glu-229, Arg-233, and Trp-50 of thrombin are necessary for direct activation
      of factor XIII. These residues define a low specificity site known to be
      important also for both protein C activation and for inhibition of thrombin by
      antithrombin. The enhancing effect of fibrinogen occurs as a consequence of its
      conversion to fibrin and subsequent polymerization. Surface residues of thrombin
      further involved in high specificity fibrin-enhanced factor XIII activation were
      identified as His-66, Tyr-71, and Asn-74. These residues represent a distinct
      interaction site on thrombin (within exosite I) also employed by thrombomodulin
      in its cofactor-enhanced activation of protein C. In competition experiments,
      thrombomodulin inhibited fibrin-enhanced factor XIII activation. Based upon these
      and prior published results, we propose that the polymerization process forms a
      fibrin cofactor that acts to approximate thrombin and factor XIII bound to
      separate and complementary domains of fibrinogen. This enables enhanced factor
      XIII activation to be localized around the fibrin clot. We also conclude that
      proximity to and competition for cofactor interaction sites primarily directs the
      fate of thrombin.

PMID- 12794067
TI  - Arabidopsis thaliana plants lacking the PSI-D subunit of photosystem I suffer
      severe photoinhibition, have unstable photosystem I complexes, and altered redox
      homeostasis in the chloroplast stroma.
AB  - The PSI-D subunit of photosystem I is a hydrophilic subunit of about 18 kDa,
      which is exposed to the stroma and has an important function in the docking of
      ferredoxin to photosystem I. We have used an antisense approach to obtain
      Arabidopsis thaliana plants with only 5-60% of PSI-D. No plants were recovered
      completely lacking PSI-D, suggesting that PSI-D is essential for a functional PSI
      in plants. Plants with reduced amounts of PSI-D showed a similar decrease in all
      other subunits of PSI including the light harvesting complex, suggesting that in
      the absence of PSI-D, PSI cannot be properly assembled and becomes degraded.
      Plants with reduced amounts of PSI-D became light-stressed even in low light
      although they exhibited high non-photochemical quenching (NPQ). The high NPQ was
      generated by upregulating the level of violaxanthin de-epoxidase and PsbS, which
      are both essential components of NPQ. Interestingly, the lack of PSI-D affected
      the redox state of thioredoxin. During the normal light cycle thioredoxin became
      increasingly oxidized, which was observed as decreasing malate dehydrogenase
      activity over a 4-h light period. This result shows that photosynthesis was close
      to normal the first 15 min, but after 2-4 h photoinhibition dominated as the
      stroma progressively became less reduced. The change in the thiol disulfide redox
      state might be fatal for the PSI-D-less plants, because reduction of thioredoxin
      is one of the main switches for the initiation of CO2 assimilation and
      photoprotection upon light exposure.

PMID- 12794068
TI  - Salt modulates the stability and lipid binding affinity of the adipocyte lipid
      binding proteins.
AB  - Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid
      binding protein that is found in adipocytes and macrophages and binds a large
      variety of intracellular lipids with high affinity. Although intracellular lipids
      are frequently charged, biochemical studies of lipid-binding proteins and their
      interactions often focus most heavily on the hydrophobic aspects of these
      proteins and their interactions. In this study, we have characterized the effects
      of KCl on the stability and lipid binding properties of ALBP. We find that added
      salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5
      kcal/mol. At 37 degrees C salt can more than double the stability of the protein.
      At the same time, salt inhibits the binding of the fluorescent lipid 1
      anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct
      displacement of the lipid from the protein. Thermodynamic linkage analysis of the
      salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one
      ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments
      show that salt reduces the rate of association between ANS and ALBP while
      simultaneously increasing the dissociation rate of ANS from the protein. We
      depict and discuss the thermodynamic linkages among stability, lipid binding, and
      salt effects for ALBP, including the use of these linkages to calculate the
      affinity of ANS for the denatured state of ALBP and its dependence on salt
      concentration. We also discuss the potential molecular origins and potential
      intracellular consequences of the demonstrated salt linkages to stability and
      lipid binding in ALBP.

PMID- 12794070
TI  - Activation of CTP:phosphocholine cytidylyltransferase alpha expression during the
      S phase of the cell cycle is mediated by the transcription factor Sp1.
AB  - An essential step during cell division is induction of phosphatidylcholine
      biosynthesis. In this pathway, CTP:phosphocholine cytidylyltransferase alpha (CT
      alpha) plays an important regulatory role. Previous studies (Golfman, L. S.,
      Bakovic, M., and Vance, D. E. (2001) J. Biol. Chem. 276, 43688-43692)
      demonstrated that CT alpha mRNA accumulates during S phase in preparation for
      cellular mitosis. We now demonstrate that increased binding of the transcription
      factor Sp1 to the proximal promoter of CT alpha is responsible for increased
      transcription during the S phase. The Sp1 binding element present in position 
      67/-62 is essential for activation, and the Sp1 site in position -31/-9 is
      required to enhance transcription. Inhibition of Sp1 expression by RNA
      interference abolished the enhanced expression of CT alpha. Immunoprecipitation
      studies demonstrated that Sp1 interacts with cyclin E, cyclin A, and cyclin
      dependent kinase 2 during the S phase. We conclude that Sp1 binding to the CT
      alpha proximal promoter is necessary to enhance transcription during the S phase.
      This is the first elucidation of a mechanism by which expression of a key enzyme
      in phospholipid biosynthesis is regulated during the cell cycle.

PMID- 12794069
TI  - The mitochondrial prohibitin complex is essential for embryonic viability and
      germline function in Caenorhabditis elegans.
AB  - Prohibitins in eukaryotes consist of two subunits (PHB1 and PHB2) that together
      form a high molecular weight complex in the mitochondrial inner membrane. The
      evolutionary conservation and the ubiquitous expression in mammalian tissues of
      the prohibitin complex suggest an important function among eukaryotes. The PHB
      complex has been shown to play a role in the stabilization of newly synthesized
      subunits of mitochondrial respiratory enzymes in the yeast Saccharomyces
      cerevisiae. We have used Caenorhabditis elegans as model system to study the role
      of the PHB complex during development of a multicellular organism. We demonstrate
      that prohibitins in C. elegans form a high molecular weight complex in the
      mitochondrial inner membrane similar to that of yeast and humans. By using RNA
      mediated gene inactivation, we show that PHB proteins are essential during
      embryonic development and are required for somatic and germline differentiation
      in the larval gonad. We further demonstrate that a deficiency in PHB proteins
      results in altered mitochondrial biogenesis in body wall muscle cells. This paper
      reports a strong loss of function phenotype for prohibitin gene inactivation in a
      multicellular organism and shows for the first time that prohibitins serve an
      essential role in mitochondrial function during organismal development.

PMID- 12794071
TI  - 20-hydroxyeicosatetraenoic acid (20-HETE) activates mouse TRPC6 channels
      expressed in HEK293 cells.
AB  - In the present study, we show that the eicosanoid compound, 20
      hydroxyeicosatetraenoic acid (20-HETE), an important arachidonic acid metabolite,
      activates mouse TRPC6 in a stable, overexpressing HEK293 cell line, Hek-t6.11.
      Application of 20-HETE rapidly induced an inward, non-selective current in whole
      cell recordings, which was inhibited by N-methyl-d-glucamine, 1.8 mm Ca2+, and
      100 microM Gd3+ but remained unaffected by flufenamate and indomethacin. The
      current-voltage relationship obtained at low concentrations of 20-HETE (1-10
      microM) demonstrated slight inward rectification, whereas the highest
      concentration of 20-HETE tested (30 microM) showed outward rectification, as
      shown previously for these channels using 100 microM 1-oleoyl-2-acetyl-sn
      glycerol. Dose-response curves indicate that 20-HETE activated TRPC6 channels
      with an EC50 = 0.8 microM. Single channel analysis using inside-out patches
      revealed that 20-HETE increased open probability of mouse TRPC6 channels
      approximately 3-fold, and this was in a membrane-delimited fashion.
      Interestingly, 20-HETE did not provoke changes in intracellular Ca2+
      concentrations. Thus, we have identified an arachidonic acid metabolite, 20-HETE,
      as a novel activator for a TRP family member, TRPC6.

PMID- 12794072
TI  - RNA polymerase subunit requirements for activation by the enhancer-binding
      protein Rhodobacter capsulatus NtrC.
AB  - Rhodobacter capsulatus NtrC is an enhancer-binding protein that activates
      transcription of the R. capsulatus sigma 70 RNA polymerase, but does not activate
      the Escherichia coli sigma 70-RNA polymerase at the nifA1 promoter. We utilized
      R. capsulatus:E. coli hybrid RNA polymerases assembled in vitro to investigate
      the subunits required for protein-protein interaction with RcNtrC at the
      nifA1mut1 promoter. Assembly of core Rc alpha beta beta' or hybrid RNA
      polymerases containing the Rc beta beta' subunits absolutely require the
      inclusion of an omega subunit, with the Ec omega subunit only partially promoting
      RNA polymerase assembly. The Rc alpha Ec beta beta' RNA polymerase is not
      activated by RcNtrC. Moreover, a mutant form of the Rc alpha lacking the alpha C
      terminal domain, when assembled with the Rc beta beta'omega and sigma 70
      subunits, is activated by RcNtrC. These results suggest that the R. capsulatus
      alpha subunit is not important for RcNtrC interaction. All hybrid RNA polymerases
      that contained the Rc beta' were activated by RcNtrC, suggesting that the Rc
      beta' subunit plays an important role. It is proposed that RcNtrC recruits R.
      capsulatus sigma 70-RNA polymerase to the promoter through interaction with Rc
      beta'. RcNtrC interacts with RNA polymerase from a unique position, with dimers
      centered at -118 bp from the start site. Placing the RcNtrC tandem binding sites
      on the opposite face of the helix (-113 bp) completely abolished transcription
      activation. Moving the RcNtrC tandem binding sites 20 bp closer to or further
      from the promoter significantly reduced activation, again suggesting unique
      spatial constraints on how RcNtrC interacts with the R. capsulatus RNA
      polymerase.

PMID- 12794073
TI  - A structural basis for half-of-the-sites metal binding revealed in Drosophila
      melanogaster porphobilinogen synthase.
AB  - Porphobilinogen synthase (PBGS) proteins fall into several distinct groups with
      different metal ion requirements. Drosophila melanogaster porphobilinogen
      synthase (DmPBGS) is the first non-mammalian metazoan PBGS to be characterized.
      The sequence shows the determinants for two zinc binding sites known to be
      present in both mammalian and yeast PBGS, proteins that differ in the exhibition
      of half-of-the-sites metal binding. The pH-dependent activity of DmPBGS is
      uniquely affected by zinc. A tight binding catalytic zinc binds at 0.5/subunit
      with a Kd well below microm. A second inhibitory zinc exhibits a Kd of
      approximately 5 microm and appears to bind at a stoichiometry of 1/subunit. A
      molecular model of DmPBGS suggests that the inhibitory zinc is located at a
      subunit interface using Cys-219 and His-10 as ligands. Zinc binding to this
      previously unknown inhibitory site is proposed to inhibit opening of the active
      site lid. As predicted, the DmPBGS mutant H10F is active but is not inhibited by
      zinc. H10F binds a catalytic zinc at 0.5/subunit and binds a second nonessential
      and noninhibitory zinc at 0.5/subunit. This result reveals a structural basis for
      half-of-the-sites metal binding that is consistent with a reciprocating motion
      model for function of oligomeric PBGS.

PMID- 12794074
TI  - Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity,
      a link for Notch and Wnt pathways.
AB  - Phosphorylation of Notch proteins has been indirectly correlated with Notch
      activation and nuclear translocation as well as cellular transformation. There is
      evidence that the Wnt signaling pathway, which results in glycogen synthase
      kinase-3 beta (GSK-3 beta) inhibition, cross-talks with the Notch pathway. In
      this study, we show that GSK-3 beta is able to bind and phosphorylate Notch2 in
      vitro and in vivo. We identify three specific phosphorylation sites in the Notch2
      serine/threonine-rich domain that are dependent on GSK-3 beta activity.
      Phosphorylation of the serine/threonine-rich domain has been shown previously to
      be crucial in regulating cytokine-specific cell differentiation.
      Coimmunoprecipitation experiments show that full-length Notch2 binds more
      efficiently than intracellular Notch2 to GSK-3 beta. Nevertheless, only the
      processed Notch2 is a substrate for the kinase, thus suggesting that GSK-3 beta
      dependent phosphorylation may be specifically regulating the activated Notch
      molecule. Consistent with this, GSK-3 beta inhibits the transcriptional
      activation of Notch target genes both in vitro and in vivo, whereas lithium
      chloride treatment or Wnt-1 overexpression that results in GSK-3 beta inhibition
      leads to the up-regulation of the Hes-1 promoter. Together, our results suggest
      that cross-talk between Notch and Wnt pathways may be partially mediated by
      specific regulation of GSK-3 beta-dependent Notch phosphorylation.

PMID- 12794075
TI  - Crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron
      chelate. Conformational change of the distal helix during the heme cleavage
      reaction.
AB  - The crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron
      chelate (biliverdin(Fe)-HO-1), the immediate precursor of the final product,
      biliverdin, has been determined at a 2.4-A resolution. The electron density in
      the heme pocket clearly showed that the tetrapyrrole ring of heme is cleaved at
      the alpha-meso edge. Like the heme bound to HO-1, biliverdin-iron chelate is
      located between the distal and proximal helices, but its accommodation state
      seems to be less stable in light of the disordering of the solvent-exposed
      propionate and vinyl groups. The middle of the distal helix is shifted away from
      the center of the active site in biliverdin(Fe)-HO-1, increasing the size of the
      heme pocket. The hydrogen-bonding interaction between Glu-29 and Gln-38,
      considered to restrain the orientation of the proximal helix in the heme-HO-1
      complex, was lost in biliverdin(Fe)-HO-1, leading to relaxation of the helix.
      Biliverdin has a distorted helical conformation; the lactam oxygen atom of its
      pyrrole ring-A interacted with Asp-140 through a hydrogen-bonding solvent
      network. Because of the absence of a distal water ligand, the iron atom is five
      coordinated with His-25 and four pyrrole nitrogen atoms. The coordination
      geometry deviates considerably from a square pyramid, suggesting that the iron
      may be readily dissociated. We speculate that the opened conformation of the heme
      pocket facilitates sequential product release, first iron then biliverdin, and
      that because of biliverdin's increased flexibility, iron release triggers its
      slow dissociation.

PMID- 12794076
TI  - Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia
      protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1
      corepressor complex to repress transcription in vivo.
AB  - Fusion proteins of retinoic acid receptor alpha (RARalpha) with promyelocytic
      leukemia protein (PML-RARalpha) or with promyelocytic leukemia zinc finger
      protein (PLZF-RARalpha) are associated with and likely responsible for the
      development of acute promyelocytic leukemia. These oncoproteins retain the
      ability to bind DNA and retinoic acid through the RARalpha moiety. This enables
      them to repress RARalpha target genes in the absence of retinoic acid, but the
      underlying mechanisms remain to be investigated. Here we use the frog oocyte
      system to study transcriptional regulation by PML-RARalpha and PLZF-RARalpha in
      the context of chromatin. We first show that the endogenous corepressor N-CoR
      forms a complex with TBLR1 (transducin beta-like protein 1-related protein) and
      that both N-CoR and TBLR1 can interact with unliganded PML-RARalpha and PLZF
      RARalpha in vivo. Using chromatin immunoprecipitation, we demonstrate that both
      oncoproteins recruit TBLR1, as well as N-CoR, to its target promoter, leading to
      histone deacetylation and transcriptional repression. Furthermore, expression of
      a dominant negative N-CoR that contains the TBLR1-interacting domain blocks
      transcription repression by unliganded PML-RARalpha and PLZF-RARalpha. Thus, our
      studies provide in vivo evidence for targeted recruitment of N-CoR-TBLR1
      complexes by PML-RARalpha and PLZF-RARalpha in transcriptional repression in the
      context of chromatin.

PMID- 12794077
TI  - A labile regulatory copper ion lies near the T1 copper site in the multicopper
      oxidase CueO.
AB  - CueO, a multicopper oxidase, is part of the copper-regulatory cue operon in
      Escherichia coli, is expressed under conditions of copper stress and shows
      enhanced oxidase activity when additional copper is present. The 1.7-A resolution
      structure of a crystal soaked in CuCl2 reveals a Cu(II) ion bound to the protein
      7.5 A from the T1 copper site in a region rich in methionine residues. The
      trigonal bipyramidal coordination sphere is unusual, containing two methionine
      sulfur atoms, two aspartate carboxylate oxygen atoms, and a water molecule. Asp
      439 both ligates the labile copper and hydrogen-bonds to His-443, which ligates
      the T1 copper. This arrangement may mediate electron transfer from substrates to
      the T1 copper. Mutation of residues bound to the labile copper results in loss of
      oxidase activity and of copper tolerance, confirming a regulatory role for this
      site. The methionine-rich portion of the protein, which is similar to that of
      other proteins involved in copper homeostasis, does not display additional copper
      binding. The type 3 copper atoms of the trinuclear cluster in the structure are
      bridged by a chloride ion that completes a square planar coordination sphere for
      the T2 copper atom but does not affect oxidase activity.

PMID- 12794078
TI  - Plasma membrane voltage-dependent anion channel mediates antiestrogen-activated
      maxi Cl- currents in C1300 neuroblastoma cells.
AB  - The cell membrane large conductance voltage-dependent chloride channel (Maxi Cl-
      channel) has been recorded in different cell types following excision of membrane
      patches or stimulation by antiestrogens under whole-cell recording conditions.
      However, both its molecular nature and relevance to cell physiology await
      elucidation. Its electrophysiological properties resemble those of the voltage
      dependent anion channel (VDAC) of the outer mitochondrial membrane. This
      observation has led to the controversial hypothesis that VDAC could be the
      molecular correlate of the plasma membrane Maxi Cl- channel. We have investigated
      the cellular localization of VDAC and its relationship with the antiestrogen
      activated Maxi Cl- current in C1300 neuroblastoma cells. The presence of a plasma
      membrane VDAC was demonstrated by immunoblotting of membrane fractions with
      monoclonal antibodies against the VDAC and by reverse transcription-PCR using
      primers that hybridize to a VDAC sequence coding for an N-terminal leader peptide
      required for its plasma membrane sorting. Besides, VDAC colocalized with markers
      of plasma membrane lipid rafts (cholera toxin beta subunit) but not caveolin-1.
      Transfection of C1300 cells with an antisense oligonucleotide directed against
      the specific membrane leader sequence of VDAC markedly reduced both VDAC
      immunostaining and antiestrogen-activated Maxi Cl- currents, suggesting that VDAC
      forms the plasma membrane Maxi Cl- channel or a part thereof.

PMID- 12794079
TI  - Utp8p is an essential intranuclear component of the nuclear tRNA export machinery
      of Saccharomyces cerevisiae.
AB  - A yeast tRNA three-hybrid interaction approach and an in vivo nuclear tRNA export
      assay based on amber suppression was used to identify proteins that participate
      in the nuclear tRNA export process in Saccharomyces cerevisiae. One of the
      proteins identified by this strategy is Utp8p, an essential 80-kDa nucleolar
      protein that has been implicated in 18 S ribosomal RNA biogenesis. Our
      characterization indicated that the major function of Utp8p is in nuclear tRNA
      export. Like the S. cerevisiae Los1p and the mammalian exportin-t, which are
      proteins known to facilitate nuclear tRNA export, overexpression of Utp8p
      restored export of tRNAamTyr mutants defective in nuclear export. Furthermore,
      depletion of Utp8p blocked nuclear export of mature tRNAs derived from both
      intronless and intron-containing pre-tRNAs but did not affect tRNA and rRNA
      maturation, nuclear export of mRNA and ribosomes, or nuclear tRNA aminoacylation.
      Overexpression of Utp8p also alleviated nuclear retention of non-aminoacylated
      tRNATyr in a tyrosyl-tRNA synthetase mutant strain. Utp8p binds tRNA directly and
      saturably, indicating that it has a tRNA-binding site. Utp8p does not appear to
      function as a tRNA export receptor, because it does not shuttle between the
      nucleus and the cytoplasm. Taken together, the results suggest that Utp8p is an
      essential intranuclear component of the nuclear tRNA export machinery, which may
      channel tRNA to the various tRNA export pathways operating in S. cerevisiae.

PMID- 12794080
TI  - TWEAK mediates signal transduction and differentiation of RAW264.7 cells in the
      absence of Fn14/TweakR. Evidence for a second TWEAK receptor.
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the
      tumor necrosis factor family that is implicated in apoptosis, proliferation,
      migration, and inflammation. We describe our findings showing that TWEAK mediated
      the differentiation of RAW264.7 (RAW) monocyte/macrophage cells into
      multinuclear, functional osteoclasts. The effect of TWEAK was direct and not
      mediated by the receptor activator of nuclear factor-kappa B (NF-kappa B) ligand
      (RANKL) as shown by the use of TWEAK- or RANKL-neutralizing antibodies and by
      osteoprotegerin, a decoy receptor for RANKL. Recently, fibroblast growth factor
      inducible 14 (Fn14) was suggested to be a receptor for TWEAK. We show that the
      Fn14/TWEAK receptor (TweakR) was not responsible for the osteoclastic effect of
      TWEAK on RAW cells. Flow cytometry analysis did not reveal the expression of
      Fn14/TweakR on RAW cells. Moreover, Fn14/TweakR-neutralizing antibodies did not
      block TWEAK-induced RAW cell differentiation into osteoclasts. This indicated
      that a second TweakR, TweakR2, exists on RAW cells and is responsible for
      mediating TWEAK-induced differentiation. We next compared the signaling pathways
      that are activated by the two receptors. TWEAK binding to TweakR2 activated the
      NF-kappa B, mitogen-activated protein kinase and c-Jun N-terminal kinase
      signaling cascades in RAW cells. In contrast, TWEAK binding to Fn14/TweakR
      activated the NF-kappa B and c-Jun N-terminal kinase pathways but induced only a
      weak activation of MAPK in HT-29 human colon adenocarcinoma cells expressing
      endogenous Fn14/TweakR. We propose that the biological effects of TWEAK are
      mediated by binding to one of at least two distinct receptors that induce
      differential activation of downstream signaling pathways.

PMID- 12794081
TI  - The biotin carboxylase-biotin carboxyl carrier protein complex of Escherichia
      coli acetyl-CoA carboxylase.
AB  - Escherichia coli acetyl-CoA carboxylase (ACC) is composed of four different
      protein molecules. These proteins form a large but very unstable complex. Hints
      of a sub-complex between the biotin carboxylase (BC) and biotin carboxyl carrier
      protein (BCCP) subunits have been reported in the literature, but the complex was
      not isolated and thus the protein stoichiometry could not be determined. We
      report isolation of the BC.BCCP complex. By use of affinity chromatography using
      two different affinity tags it was shown that the complex consists of a two BCCP
      molecules per BC molecule. The molar ratio in the complex is the same as the
      ratio of the subunit proteins synthesized in vivo. We conclude that the complex
      consists of a dimer of BC plus four BCCP molecules instead of the 2BC.2BCCP
      complex previously assumed. This subunit ratio allows two conflicting models of
      the ACC mechanism to be rectified. We also report that the N-terminal 30 or so
      residues of BCCP are responsible for the interaction of BCCP with BC and that the
      BC.BCCP complex is a substrate for biotinylation in vitro.

PMID- 12794082
TI  - Roles of specific isoforms of protein kinase C in the transcriptional control of
      cyclin D1 and related genes.
AB  - Although protein kinase C (PKC) has been implicated in cell cycle progression,
      cell proliferation, and tumor promotion, the precise roles of specific isoforms
      in these processes is not clear. Therefore, we constructed and analyzed a series
      of expression vectors that encode hemagglutinin-tagged wild type (WT),
      constitutively active mutants (Delta NPS and CAT), and dominant negative mutants
      of PKCs alpha, beta 1, beta 2, gamma, delta, epsilon, eta, zeta, and iota. Cyclin
      D1 promoter reporter assays done in serum-starved NIH3T3 cells indicated that the
      constitutively active mutants of PKC-alpha and PKC-epsilon were the most potent
      activators of this reporter, whereas the constitutively active mutant of PKC
      delta inhibited its activity. Transient transfection studies with a series of 5'
      deleted cyclin D1 promoter constructs showed that the proximal 964-base region,
      which contains AP-1, SP1, and CRE enhancer elements, is required for activation
      of the cyclin D1 promoter by PKC-alpha. Deletion of the AP-1 enhancer element
      located at position -954 upstream from the initiation site abolished PKC-alpha
      dependent activation of cyclin D1 expression. Deletion of the SP1 or CRE enhancer
      elements did not have any effect. A dominant negative mutant of c-Jun inhibited
      activation of the cyclin D1 promoter in a concentration-dependent manner,
      providing further evidence that AP-1 activity is required for activation of the
      cyclin D1 promoter by PKC-alpha and PKC-epsilon. The constitutively active
      mutants of PKC-alpha and PKC-epsilon also activated c-fos, c-jun, and cyclin E
      promoter activity. Furthermore, NIH3T3 cells that stably express the
      constitutively active mutants of PKC-alpha or PKC-epsilon displayed increased
      expression of endogenous cyclins D1 and E and faster growth rates. These results
      provide evidence that the activation of PKC-alpha or PKC-epsilon in mouse
      fibroblasts can play an important role in enhancing cell cycle progression and
      cell proliferation.

PMID- 12794083
TI  - Sequence specificity in the interaction of Bluetongue virus non-structural
      protein 2 (NS2) with viral RNA.
AB  - The non-structural protein NS2 of Bluetongue virus (BTV) is synthesized
      abundantly in virus-infected cells and has been suggested to be involved in virus
      replication. The protein, with a high content of charged residues, possesses a
      strong affinity for single-stranded RNA species but, to date, all studies have
      failed to identify any specificity in the NS2-RNA interaction. In this report, we
      have examined, through RNA binding assays using highly purified NS2, the
      specificity of interaction with different single-stranded RNA (ssRNA) species in
      the presence of appropriate competitors. The data obtained show that NS2 indeed
      has a preference for BTV ssRNA over nonspecific RNA species and that NS2
      recognizes a specific region within the BTV10 segment S10. The secondary
      structure of this region was determined and found to be a hairpin-loop with
      substructures within the loop. Modification-inhibition experiments highlighted
      two regions within this structure that were protected from ribonuclease cleavage
      in the presence of NS2. Overall, these data imply that a function of NS2 may be
      to recruit virus messenger RNAs (that also act as templates for synthesis of
      genomic RNAs) selectively from other RNA species within the infected cytosol of
      the cell during virus replication.

PMID- 12794084
TI  - Insights into the conformational equilibria of maltose-binding protein by
      analysis of high affinity mutants.
AB  - The affinity of maltose-binding protein (MBP) for maltose and related
      carbohydrates was greatly increased by removal of groups in the interface
      opposite the ligand binding cleft. The wild-type protein has a KD of 1200 nM for
      maltose; mutation of residues Met-321 and Gln-325, both to alanine, resulted in a
      KD for maltose of 70 nM; deletion of 4 residues, Glu-172, Asn-173, Lys-175, and
      Tyr-176, which are part of a poorly ordered loop, results in a KD for maltose of
      110 nM. Combining the mutations yields an increased affinity for maltodextrins
      and a KD of 6 nM for maltotriose. Comparison of ligand binding by the mutants,
      using surface plasmon resonance spectroscopy, indicates that decreases in the off
      rate are responsible for the increased affinity. Small-angle x-ray scattering was
      used to demonstrate that the mutations do not significantly affect the solution
      conformation of MBP in either the presence or absence of maltose. The crystal
      structures of selected mutants showed that the mutations do not cause significant
      structural changes in either the closed or open conformation of MBP. These
      studies show that interactions in the interface opposite the ligand binding
      cleft, which we term the "balancing interface," are responsible for modulating
      the affinity of MBP for its ligand. Our results are consistent with a model in
      which the ligand-bound protein alternates between the closed and open
      conformations, and removal of interactions in the balancing interface decreases
      the stability of the open conformation, without affecting the closed
      conformation.

PMID- 12794085
TI  - The role of collagen structure in mitogen stimulation of ERK, cyclin D1
      expression, and G1-S progression in rat hepatocytes.
AB  - Adhesion to type 1 collagen can elicit different cellular responses dependent
      upon whether the collagen is in a fibrillar form (gel) or monomeric form (film).
      Hepatocytes adherent to collagen film spread extensively, express cyclin D1, and
      increase DNA synthesis in response to epidermal growth factor, whereas
      hepatocytes adherent to collagen gel have increased differentiated function, but
      lower DNA synthesis. The signaling mechanisms by which different forms of type I
      collagen modulate cell cycle progression are unknown. When ERK MAP kinase
      activation was analyzed in hepatocytes attached to collagen film, two peaks of
      ERK activity were demonstrated. Only the second peak, which correlated with an
      increase of cyclin D1, was required for G1-S progression. Notably, this second
      peak of ERK activity was absent in cells adherent to collagen gel, but not
      required in the presence of exogenous cyclin D1. Expression of activated mutants
      of the Ras/Raf/MEK signaling pathway in cells adherent to collagen gel restored
      ERK phosphorylation and DNA synthesis, but differentially affected cell shape.
      Although Ras, Raf, and MEK all increased expression of cyclin D1 on collagen
      film, only Ras and Raf significantly up-regulated cyclin D1 levels on collagen
      gel. These results demonstrate that adhesion to polymerized collagen induces
      growth arrest by inhibiting the Ras/ERK-signaling pathway to cyclin D1 required
      in late G1.

PMID- 12794087
TI  - Activation of ERK induces phosphorylation of MAPK phosphatase-7, a JNK specific
      phosphatase, at Ser-446.
AB  - We previously showed that MKP-7 suppresses MAPK activation in COS-7 cells in the
      order of selectivity, JNK >> p38 > ERK, but interacts with ERK as well as JNK and
      p38. In this study we found that, when expressed in COS-7 cells with HA-ERK2, the
      mobility of FLAG-MKP-7 was decreased on SDS-PAGE gels depending on several
      stimuli, including phorbol 12-myristate 13-acetate, fetal bovine serum, epidermal
      growth factor, H2O2, and ionomycin. By using U0126, a MEK inhibitor, and
      introducing several point mutations, we demonstrated that this upward mobility
      shift is because of phosphorylation and identified Ser-446 of MKP-7 as the
      phosphorylation site targeted by ERK activation. To determine how MKP-7 interacts
      with MAPKs, we identified three domains in MKP-7 required for interaction with
      MAPKs, namely, putative MAP kinase docking domains (D-domain) I and II and a long
      COOH-terminal stretch unique to MKP-7. The D-domain I is required for interaction
      with ERK and p38, whereas the D-domain II is required for interaction with JNK
      and p38, which is likely to be important for MKP-7 to suppress JNK and p38
      activations. The COOH-terminal stretch of MKP-7 was shown to determine JNK
      preference for MKP-7 by masking MKP-7 activity toward p38 and is a domain bound
      by ERK. These data strongly suggested that Ser-446 of MKP-7 is phosphorylated by
      ERK.

PMID- 12794086
TI  - Differential ubiquitination defines the functional status of the tumor suppressor
      Smad4.
AB  - Smad4 is an essential signal transducer of all transforming growth factor-beta
      (TGF-beta) superfamily pathways that regulate cell growth and differentiation,
      and it becomes inactivated in human cancers. Receptor-activated (R-) Smads can be
      poly-ubiquitinated in the cytoplasm or the nucleus, and this regulates their
      steady state levels or shutdown of the signaling pathway. Oncogenic mutations in
      Smad4 and other Smads have been linked to protein destabilization and proteasomal
      degradation. We analyzed a panel of missense mutants derived from human cancers
      that map in the N-terminal Mad homology (MH) 1 domain of Smad4 and result in
      protein instability. We demonstrate that all mutants exhibit enhanced poly
      ubiquitination and proteasomal degradation. In contrast, wild type Smad4 is a
      relatively stable protein that undergoes mono- or oligo-ubiquitination, a
      modification not linked to protein degradation. Analysis of Smad4 deletion
      mutants indicated efficient mono- or oligo-ubiquitination of the C-terminal MH2
      domain. Mass spectrometric analysis of mono-ubiquitinated Smad4 MH2 domain
      identified lysine 507 as a major target for ubiquitination. Lysine 507 resides in
      the conserved L3 loop of Smad4 and participates in R-Smad C-terminal
      phosphoserine recognition. Mono- or oligo-ubiquitinated Smad4 exhibited enhanced
      ability to oligomerize with R-Smads, whereas mutagenesis of lysine 507 led to
      inefficient Smad4/R-Smad hetero-oligomerization and defective transcriptional
      activity. Finally, overexpression of a mutant ubiquitin that only leads to mono
      ubiquitination of Smad4 enhanced Smad transcriptional activity. These data
      suggest that oligo-ubiquitination positively regulates Smad4 function, whereas
      poly-ubiquitination primarily occurs in unstable cancer mutants and leads to
      protein degradation.

PMID- 12794088
TI  - The functional glycosyltransferase signature sequence of the human beta 1,3
      glucuronosyltransferase is a XDD motif.
AB  - The human beta 1,3-glucuronosyltransferase I (GlcAT-I) is the key enzyme
      responsible for the completion of glycosaminoglycan-protein linkage
      tetrasaccharide of proteoglycans (GlcA beta 1,3Gal beta 1,3Gal beta 1,4Xyl beta 1
      O-serine). We have investigated the role of aspartate residues Asp194-Asp195
      Asp196 corresponding to the glycosyltransferase DXD signature motif, in GlcAT-I
      function by UDP binding experiments, kinetic analyses, and site-directed
      mutagenesis. We presented the first evidence that Mn2+ is not only essential for
      GlcAT-I activity but is also required for cosubstrate binding. In agreement,
      kinetic studies were consistent with a metal-activated enzyme model whereby
      activation probably occurs via binding of a Mn2+.UDP-GlcA complex to the enzyme.
      Mutational analysis showed that the Asp194-Asp195-Asp196 motif is a major element
      of the UDP/Mn2+ binding site. Furthermore, determination of the individual role
      of each aspartate showed that substitution of Asp195 as well as Asp196 to alanine
      strongly impaired GlcAT-I activity, whereas Asp194 replacement produced only a
      moderate alteration of the enzyme activity. These findings along with molecular
      modeling and three-dimensional structure comparison of the GlcAT-I catalytic
      center with that of the Bacillus subtilis glycosyltransferase SpsA provided
      evidence that the interactions of Asp195 with the ribose moiety of UDP and of
      Asp196 with the metal cation Mn2+ were crucial for GlcAT-I function. Altogether,
      these results indicated that, similarly to the SpsA enzyme, the nucleotide
      binding site of GlcAT-I contains a XDD motif rather than a DXD motif.

PMID- 12794089
TI  - Airway hyperresponsiveness: from molecules to bedside.

PMID- 12794090
TI  - Effects of gravity on lung diffusing capacity and cardiac output in prone and
      supine humans.
AB  - Both in normal subjects exposed to hypergravity and in patients with acute
      respiratory distress syndrome, there are increased hydrostatic pressure gradients
      down the lung. Also, both conditions show an impaired arterial oxygenation, which
      is less severe in the prone than in the supine posture. The aim of this study was
      to use hypergravity to further investigate the mechanisms behind the differences
      in arterial oxygenation between the prone and the supine posture. Ten healthy
      subjects were studied in a human centrifuge while exposed to 1 and 5 times normal
      gravity (1 G, 5 G) in the anterioposterior (supine) and posterioanterior (prone)
      direction. They performed one rebreathing maneuver after approximately 5 min at
      each G level and posture. Lung diffusing capacity decreased in hypergravity
      compared with 1 G (ANOVA, P = 0.002); it decreased by 46% in the supine posture
      compared with 25% in the prone (P = 0.01 for supine vs. prone). At the same time,
      functional residual capacity decreased by 33 and 23%, respectively (P < 0.001 for
      supine vs. prone), and cardiac output by 40 and 31% (P = 0.007 for supine vs.
      prone), despite an increase in heart rate of 16 and 28% (P < 0.001 for supine vs.
      prone), respectively. The finding of a more impaired diffusing capacity in the
      supine posture compared with the prone at 5 G supports our previous observations
      of more severe arterial hypoxemia in the supine posture during hypergravity. A
      reduced pulmonary-capillary blood flow and a reduced estimated alveolar volume
      can explain most of the reduction in diffusing capacity when supine.

PMID- 12794092
TI  - Exercise training improves conduit vessel function in patients with coronary
      artery disease.
AB  - It is well established that endothelial dysfunction is present in coronary artery
      disease (CAD), although few studies have determined the effect of training on
      peripheral conduit vessel function in patients with CAD. A randomized, crossover
      design determined the effect of 8 wk of predominantly lower limb, combined
      aerobic and resistance training, in 10 patients with treated CAD. Endothelium
      dependent dilation of the brachial artery was determined, by using high
      resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after
      ischemia. Endothelium-independent vasodilation was measured after administration
      of glyceryl trinitrate (GTN). Baseline function was compared with that of 10
      control subjects. Compared with matched healthy control subjects, FMD and GTN
      responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8
      (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P <
      0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8
      to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1
      +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent
      conduit vessel dilation in subjects with CAD, and the effect, evident in the
      brachial artery, appears to be generalized rather than limited to vessels of
      exercising muscle beds. These results provide evidence for the benefit of
      exercise training, as an adjunct to routine therapy, in patients with a history
      of CAD.

PMID- 12794091
TI  - Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse
      chromosome 5.
AB  - We hypothesized that upper airway obstruction (UAO) leads to a compensatory
      increase in the duty cycle [ratio of inspiratory time to respiratory cycle length
      (Ti/Tt)], which is determined by genetic factors. We examined the compensatory
      Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2).
      hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and
      their first- and second-generation (F2) offspring. 3). We then used the
      compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse
      genome. First, normal individuals exhibited a similar increase in the Ti/Tt
      during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared
      with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6
      progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was
      significantly (P < 0.01) greater than that of the two progenitors. Third, with a
      peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are
      genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse
      chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and
      B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological
      plausibility in mechanisms of upper airway patency and chemosensitivity,
      respectively. In summary, Ti/Tt may serve as an intermediate physiological
      phenotype for compensatory neuromuscular response mechanisms for maintaining
      ventilation in the face of UAO and hypoventilation and to help target specific
      candidate genes that may play a role in the expression of sleep-disordered
      breathing.

PMID- 12794093
TI  - Paradoxical effects of prior activity on human sarcoplasmic reticulum Ca2+-ATPase
      response to exercise.
AB  - To investigate the effects of intermittent heavy exercise (HE) on sarcoplasmic
      reticulum (SR) maximal Ca2+-ATPase activity (Vmax) and Ca2+ uptake, a continuous
      two-stage standardized cycling test was performed before and after HE by
      untrained men [peak aerobic power (Vo -->Vo2 peak) = 42.9 +/- 2.7 ml. kg-1 x min
      1]. The HE consisted of 16 bouts of cycling performed for 6 min each hour at 90%
      Vo2 peak. Tissue was obtained from the vastus lateralis by needle biopsy before
      and during each cycle test. Before HE, reductions (P < 0.05 micromol. g protein
      1x min-1) of 16 and 31% were observed in Vmax and Ca2+ uptake, respectively,
      after 40 min of the standardized test. Resting Vmax and Ca2+ uptake were
      depressed (P < 0.05) by 19 and 30%, respectively, when measured 36-48 h after HE.
      During the standardized test, after HE, Vmax increased (P < 0.05) by 20%, whereas
      no change was observed in Ca2+ uptake. The HE protocol resulted in small
      increases (P < 0.05) and decreases (P < 0.05) in sarco(endo)plasmic reticulum
      Ca2+-ATPase (SERCA) 2a and SERCA1 expression, respectively, as determined by
      Western blotting techniques. These results indicate that SR Ca2+-sequestering
      function in response to a prolonged exercise test depends on prior activity
      status, such that rested muscles exhibit a decrease and prior exercised muscles,
      an increase in Ca2+-ATPase activity. Moreover, it appears that changes in SERCA
      content can occur in response to a sustained session of intermittent exercise.

PMID- 12794094
TI  - Augmentation of the push-pull effect by terminal aortic occlusion during head
      down tilt.
AB  - Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced
      when positive Gz stress is preceded by exposure to hypogravity, which is called
      the "push-pull effect." The purpose of this study was to test the hypothesis that
      baroreceptor reflexes contribute to the push-pull effect by augmenting the
      magnitude of simulated hypogravity and thereby augmenting the stimulus to the
      baroreceptors. We used eye-level blood pressure as a measure of the effectiveness
      of the blood pressure regulatory systems. The approach was to augment the
      magnitude of the carotid hypertension (and the hindbody hypotension) when
      hypogravity was simulated by head-down tilt by mechanically occluding the
      terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley
      rats were instrumented with a carotid artery catheter and a pneumatic vascular
      occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were
      restrained and subjected to a control gravitational (G) profile that consisted of
      rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G
      profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for
      2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile
      consisted of terminal aortic vascular occlusion during 2 s of head-down tilt
      followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude
      of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/-
      0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull
      conditions, respectively, with all three pairwise comparisons achieving
      statistically significant differences (P < 0.01). Thus augmentation of negative
      Gz stress with vascular occlusion increased the magnitude of the push-pull effect
      in anesthetized rats subjected to tilting.

PMID- 12794095
TI  - Hypotensive effect of push-pull gravitational stress occurs after autonomic
      blockade.
AB  - The "push-pull" effect denotes the reduced tolerance to +Gz (hypergravity) when
      +Gz stress is preceded by exposure to hypogravity, i.e., fractional, zero, or
      negative Gz. Previous studies have implicated autonomic reflexes as a mechanism
      contributing to the push-pull effect. The purpose of this study was to test the
      hypothesis that nonautonomic mechanisms can cause a push-pull effect, by using
      eye-level blood pressure as a measure of G tolerance. The approach was to impose
      control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head
      up tilt immediately preceded by 10 s of -15 degrees headdown tilt) gravitational
      stress after administration of hexamethonium (10 mg/kg) to inhibit autonomic
      ganglionic neurotransmission in four dogs. The animals were chronically
      instrumented with arterial and venous catheters, an ascending aortic blood flow
      transducer, ventricular pacing electrodes, and atrioventicular block. The animals
      were paced at 75 beats/min throughout the experiment. The animals were sedated
      with acepromazine and lightly restrained in lateral recumbency on a tilt table.
      After the onset of head-up tilt, the magnitude of the fall in eye-level blood
      pressure from baseline was -27.6 +/- 2.3 and -37.9 +/- 2.7 mmHg for the control
      and push-pull trials, respectively (P < 0.05). Cardiac output fell similarly in
      both conditions. Thus a push-pull effect attributable to a rise in total vascular
      conductance occurs when autonomic function is inhibited.

PMID- 12794096
TI  - Metabolic cost of generating muscular force in human walking: insights from load
      carrying and speed experiments.
AB  - We sought to understand how leg muscle function determines the metabolic cost of
      walking. We first indirectly assessed the metabolic cost of swinging the legs and
      then examined the cost of generating muscular force during the stance phase. Four
      men and four women walked at 0.5, 1.0, 1.5, and 2.0 m/s carrying loads equal to
      0, 10, 20, and 30% body mass positioned symmetrically about the waist. The net
      metabolic rate increased in nearly direct proportion to the external mechanical
      power during moderate-speed (0.5-1.5 m/s) load carrying, suggesting that the cost
      of swinging the legs is relatively small. The active muscle volume required to
      generate force on the ground and the rate of generating this force accounted for
      >85% of the increase in net metabolic rate across moderate speeds and most
      loading conditions. Although these factors explained less of the increase in
      metabolic rate between 1.5 and 2.0 m/s ( approximately 50%), the cost of
      generating force per unit volume of active muscle [i.e., the cost coefficient
      (k)] was similar across all conditions [k = 0.11 +/- 0.03 (SD) J/cm3]. These data
      indicate that, regardless of the work muscles do, the metabolic cost of walking
      can be largely explained by the cost of generating muscular force during the
      stance phase.

PMID- 12794097
TI  - Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to
      simulated microgravity.
AB  - This study was designed to compare the effectiveness of daily short-duration -Gx
      gravity exposure in preventing adverse changes in skeletal and cardiac muscles
      and bone due to simulated microgravity. Tail suspension for 28 days was used to
      simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G
      for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used
      to provide -Gx gravitation as a countermeasure. The results indicate that the
      minimum gravity exposure requirements vary greatly in different systems. Cardiac
      muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD
      was sufficient to prevent adverse changes in myocardial contractility; bone is
      most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse
      changes in physical and mechanical properties of the femur. The responsiveness of
      skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction
      and histomorphometric changes in the soleus muscle during a 28-day simulation
      period. Increasing gravitational intensity to 2.6 G showed less benefit or no
      additional benefit in preventing adverse changes in muscle and bone. The present
      work suggests that system specificity in responsiveness to intermittent gravity
      exposure should be considered one of the prerequisites in proposing intermittent
      artificial gravity as a potential countermeasure.

PMID- 12794098
TI  - Comparison of elastic properties and contractile responses of isolated airway
      segments from mature and immature rabbits.
AB  - Immature rabbits have greater maximal airway narrowing with bronchoconstriction
      in vivo compared with mature animals. As isolated immature lungs have a lower
      shear modulus, it is unclear whether the greater airway narrowing in the immature
      lung is secondary to less tethering between the airways and the lung parenchyma
      or to differences in the mechanical properties of the mature and immature
      airways. In the present study, we compared the mechanical properties of fluid
      filled, isolated, intraparenchymal airway segments of the same generation from
      mature and immature rabbits. Stimulation with ACh resulted in greater airway
      narrowing in immature than mature bronchi. The immature bronchi were more
      compliant, had a lower resting airway volume, and were more collapsible compared
      with the mature bronchi. When the airways were contracted with ACh under
      isovolume conditions, the immature bronchi generated greater active pressure, and
      they were more sensitive to ACh than were mature bronchi. Our results suggest
      that maturational differences in the structure and function of the airways in the
      absence of the lung parenchyma can account for the greater maximal narrowing of
      immature than mature airways in vivo.

PMID- 12794099
TI  - Histamine alters E-cadherin cell adhesion to increase human airway epithelial
      permeability.
AB  - During the immediate response to an inhaled allergen, there is an increase in the
      paracellular permeability of the airway epithelium.1 Histamine is an important
      agonist released during the immediate response to inhaled allergen. We
      hypothesized that histamine would increase human airway epithelial paracellular
      permeability and that it would do this by interrupting E-cadherin-based cell
      adhesion. Histamine, applied to the basolateral surface, increased the
      paracellular permeability of cultured human airway epithelia, and this effect of
      histamine was blocked by the histamine receptor antagonist promethazine. ECV304
      cells express a histamine receptor, N-cadherin, and elements of the tight
      junction, including claudins, but they do not express E-cadherin. Histamine
      increased the paracellular permeability of ECV304 cells transfected with a vector
      and expressing E-cadherin but not ECV304 cells expressing lac-Z in the same
      vector. L cells do not express the histamine receptor, cadherins, or claudins.
      Histamine decreased adhesion of L cells expressing the human histamine receptor
      and E-cadherin to an E-cadherin-Fc fusion protein. Histamine did not alter the
      adhesion to the E-cadherin fusion protein of L cells expressing either the
      histamine receptor or E-cadherin alone. When applied to the apical surface,
      adenovirus poorly infects airway epithelial cells because its receptor, CAR, is
      restricted to the basolateral surface of the cells. When histamine was applied to
      the basolateral surface of airway epithelial cells, infection of the cells by
      adenovirus increased by approximately one log. This effect of histamine was also
      blocked by promethazine. Histamine increases airway paracellular permeability and
      increases susceptibility of airway epithelial cells to infection by adenovirus by
      interrupting E-cadherin adhesion.

PMID- 12794101
TI  - Airway wall remodeling: friend or foe?
AB  - Airway wall remodeling is well documented for asthmatic airways and is believed
      to result from chronic and/or short-term exposure to inflammatory stimuli. Airway
      wall remodeling can contribute to airway narrowing as well as to the airway
      hyperresponsiveness, which is a characteristic abnormality in asthma. However,
      the potential for airway narrowing could be much worse if it were not for some of
      the protective effects of remodeling that may help to limit airway narrowing in
      asthmatic patients. This minireview discusses the evidence for airway wall
      remodeling and its effects, friend and/or foe, on airway narrowing in asthmatic
      patients.

PMID- 12794100
TI  - The first three minutes: smooth muscle contraction, cytoskeletal events, and soft
      glasses.
AB  - Smooth muscle exhibits biophysical characteristics and physiological behaviors
      that are not readily explained by present paradigms of cytoskeletal and cross
      bridge mechanics. There is increasing evidence that contractile activation of the
      smooth muscle cell involves an array of cytoskeletal processes that extend beyond
      cross-bridge cycling and the sliding of thick and thin filaments. We review here
      the evidence suggesting that the biophysical and mechanical properties of the
      smooth muscle cell reflect the integrated interactions of an array of highly
      dynamic cytoskeletal processes that both react to and transform the dynamics of
      cross-bridge interactions over the course of the contraction cycle. The
      activation of the smooth muscle cell is proposed to trigger dynamic remodeling of
      the actin filament lattice within cellular microdomains in response to local
      mechanical and pharmacological events, enabling the cell to adapt to its external
      environment. As the contraction progresses, the cytoskeletal lattice stabilizes,
      solidifies, and forms a rigid structure well suited for transmission of tension
      generated by the interaction of myosin and actin. The integrated molecular
      transitions that occur within the contractile cycle are interpreted in the
      context of microscale agitation mechanisms and resulting remodeling events within
      the intracellular microenvironment. Such an interpretation suggests that the
      cytoskeleton may behave as a glassy substance whose mechanical function is
      governed by an effective temperature.

PMID- 12794104
TI  - Tryptophan catabolism and regulation of adaptive immunity.

PMID- 12794105
TI  - Cutting edge: influence of the TCR V beta domain on the avidity of CD1d:alpha
      galactosylceramide binding by invariant V alpha 14 NKT cells.
AB  - CD1d tetramers loaded with alpha-galactosylceramide (alpha-GalCer) bind
      selectively to mouse invariant Valpha14 (Valpha14i) NKT cells and their human
      counterparts. Whereas tetramer binding strictly depends on the expression of a
      Valpha14-Jalpha18 chain in murine NKT cells, the associated beta-chain (typically
      expressing Vbeta8.2 or Vbeta7) appears not to influence tetramer binding. In this
      study, we describe novel alpha-GalCer-loaded mouse and human CD1d-IgG1 dimers,
      which revealed an unexpected influence of the TCR-beta chain on the avidity of
      CD1d:alpha-GalCer binding. A subset of Valpha14i NKT cells clearly discriminated
      alpha-GalCer bound to mouse or human CD1d on the basis of avidity differences
      conferred by the Vbeta domain of the TCR-beta chain, with Vbeta8.2 conferring
      higher avidity binding than Vbeta7.

PMID- 12794106
TI  - Cutting edge: B cell receptor signals regulate BLyS receptor levels in mature B
      cells and their immediate progenitors.
AB  - This study examines how B lymphocyte stimulator (BLyS) receptor expression and
      responsiveness are influenced by B cell receptor (BcR) signaling. Our results
      show that resting and BcR-stimulated B cells are dependent on BLyS for survival
      and that B cells remain BLyS responsive during BcR-induced activation. Further,
      BcR ligation up-regulates expression of the BLySR B cell maturation defect/BLySR3
      (Bcmd/BR3), but not other known BLySRs. Finally, the coupling of BcR signaling
      with Bcmd/BR3 expression is limited to late transitional and mature B cells.
      Together, these findings establish the coupling of BcR signaling with Bcmd/BR3
      expression as a fundamental aspect of follicular B cell selection, survival, and
      activation.

PMID- 12794107
TI  - Tapasin-/- and TAP1-/- macrophages are deficient in vacuolar alternate class I
      MHC (MHC-I) processing due to decreased MHC-I stability at phagolysosomal pH.
AB  - Alternate class I MHC (MHC-I) Ag processing via cytosolic or vacuolar pathways
      leads to cross-presentation of exogenous Ag to CD8 T cells. Vacuolar alternate
      MHC-I processing involves phagolysosomal Ag proteolysis and peptide binding to
      MHC-I in post-Golgi compartments. We report the first study of alternate MHC-I Ag
      processing in tapasin(-/-) cells and experiments with tapasin(-/-) and TAP1(-/-)
      macrophages that characterize alternate MHC-I processing. Tapasin promotes
      retention of MHC-I in the endoplasmic reticulum (ER) for loading with high
      affinity peptides, whereas tapasin(-/-) cells allow poorly loaded MHC-I molecules
      to exit the ER. Hypothetically, we considered that a large proportion of post
      Golgi MHC-I on tapasin(-/-) cells might be peptide-receptive, enhancing alternate
      MHC-I processing. In contrast, alternate MHC-I processing was diminished in both
      tapasin(-/-) and TAP1(-/-) macrophages. Nonetheless, these cells efficiently
      presented exogenous peptide, suggesting a loss of MHC-I stability or function
      specific to vacuolar processing compartments. Tapasin(-/-) and TAP1(-/-)
      macrophages had decreased MHC-I stability and increased susceptibility of MHC-I
      to inactivation by acidic conditions (correlating with vacuolar pH). Incubation
      of tapasin(-/-) or TAP1(-/-) cells at 26 degrees C decreased susceptibility of
      MHC-I to acid pH and reversed the deficiency in alternate MHC-I processing. Thus,
      tapasin and TAP are required for MHC-I to bind ER-derived stabilizing peptides to
      achieve the stability needed for alternate MHC-I processing via peptide exchange
      in acidic vacuolar processing compartments. Acidic pH destabilizes MHC-I, but
      also promotes peptide exchange, thereby enhancing alternate MHC-I Ag processing.
      These results are consistent with alternate MHC-I Ag processing mechanisms that
      involve binding of peptides to MHC-I within acidic vacuolar compartments.

PMID- 12794108
TI  - Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1
      signaling pathways involved in T cell development.
AB  - We have characterized the function of Notch-regulated ankyrin-repeat protein
      (Nrarp) in mouse cell lines and in hematopoietic stem cells (HSCs). Nrarp
      overexpression is able to block Notch-induced activation of CBF-1. In AKR1010
      thymoma cells, Nrarp overexpression blocks CBF-1-dependent transcriptional
      activation of Notch-responsive genes and inhibits phenotypic changes associated
      with Notch activation. Enforced expression of Nrarp in mouse HSCs results in a
      profound block in T lineage commitment and progression through early stages of
      thymocyte maturation. In contrast, Deltex-1 overexpression in HSCs can also block
      T lineage commitment but not progression through the early double negative stages
      of thymocyte maturation. The different effects of Deltex-1 and Nrarp
      overexpression suggest that alternate Notch signaling pathways mediate T vs B
      lineage commitment and thymocyte maturation.

PMID- 12794109
TI  - CTLA-4. FasL induces alloantigen-specific hyporesponsiveness.
AB  - The APC:T cell interface can be effectively targeted with immunotherapeutic
      proteins. We previously described a unique trans signal converter protein, CTLA
      4. Fas ligand (FasL), that has the inherent capacities to tether the T cell
      inhibitor FasL (CD95 ligand) to the surfaces of B7 (CD80 and CD86)-positive APC
      (via CTLA-4:B7 interaction), and in so doing, to simultaneously interfere with B7
      to-CD28 T cell activation signals. Given the continuing need for agents capable
      of inducing allograft tolerance without generalized immunosuppression, we have
      explored in depth the functional activity of CTLA-4. FasL in human allogeneic
      MLR. CTLA-4. FasL inhibits 1 degrees MLR and induces specific hyporesponsiveness
      in 2 degrees MLR, with both effects only partially reversible with exogenous IL
      2. Moreover, the presence of exogenous IL-2 during the 1 degrees MLR does not
      affect the induction of hyporesponsiveness upon restimulation. Furthermore, CTLA
      4. FasL enables partial activation of allostimulated T cells, reduces the
      fraction of actively dividing cells, and increases the percentage of dead cells
      among dividing T cells. Taken together, these findings suggest that CTLA-4. FasL
      mediated inhibition of secondary alloantigenic responses involves both anergy
      induction and clonal deletion. Thus, CTLA-4. FasL, a paradigmatic trans signal
      converter protein, manifests unique functional properties and emerges as a
      potentially useful immunotherapeutic for modulating alloresponsiveness.

PMID- 12794110
TI  - Proliferation and survival of activated B cells requires sustained antigen
      receptor engagement and phosphoinositide 3-kinase activation.
AB  - In this study, we investigate the extracellular and intracellular signals that
      drive cell cycle progression of activated B cells in the absence of T cell help.
      We find that brief engagement of the B cell receptor is sufficient to induce a
      single cell division in a fraction of cells, but that survival during successive
      cell divisions requires sustained receptor stimulation. In contrast, T cells have
      been shown previously to commit to multiple cell divisions following brief TCR
      engagement. Both early and late B cell receptor signals are blocked by inhibitors
      of phosphoinositide 3-kinase and mammalian target of rapamycin and are associated
      with S6 kinase activation and increased cell size. The requirement for ongoing Ag
      receptor signaling can be overcome by engagement of CD40 but only partially by IL
      4. Proliferation driven by LPS also requires sustained exposure to the stimulus.
      These findings reveal checkpoints that may limit T-independent B cell responses
      when Ag exposure is transient.

PMID- 12794111
TI  - Minor histocompatibility antigens on canine hemopoietic progenitor cells.
AB  - Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA)
      provides a promising way to treat leukemia relapse in allogeneic chimeras. Here
      we describe the in vitro generation of CTL against mHA in the dog. We tested
      their inhibitory effect on the growth of hemopoietic progenitor cells stimulated
      by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by
      coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs
      were characterized by morphology, high expression of MHC class II and CD1a, and
      the absence of the monocyte-specific marker CD14. Characteristically these cells
      stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag
      (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex
      vivo by coculture with DCs of DLA-identical littermates or in vivo by
      immunization of the responder with DCs obtained from a DLA-identical littermate.
      In suspension culture assays the growth of hemopoietic progenitor cells was
      inhibited in 53% of DLA-identical littermate combinations. In canine families mHA
      segregated with DLA as restriction elements. One-way reactivity against mHA was
      found in five littermate combinations. In two cases mHA might be Y chromosome
      associated, in three cases autosomally inherited alleles were detected. We
      conclude that CTL can be produced in vitro and in vivo against mHA on canine
      hemopoietic progenitor cells using bone marrow-derived DCs.

PMID- 12794112
TI  - Atrial natriuretic peptide polarizes human dendritic cells toward a Th2-promoting
      phenotype through its receptor guanylyl cyclase-coupled receptor A.
AB  - Atrial natriuretic peptide (ANP) is a cardiovascular hormone secreted mainly by
      the cardiac atria and regulates the volume-pressure homeostasis. The action of
      ANP is mediated by its receptor, guanylyl cyclase-coupled receptor A (GC-A). In
      this study, we explored the possibility that ANP and GC-A may play a role in the
      dendritic cell (DC)-mediated immune regulation. We first examined the expression
      of GC-A in human monocyte-derived DCs in comparison with monocytes and found that
      DCs but not monocytes express GC-A at both the mRNA and protein levels. DCs
      responded to ANP with an increase in intracellular cGMP in a dose-dependent
      manner, indicating that GC-A expressed on DCs is functional. Furthermore,
      treatment of DCs with ANP decreased production of IL-12 and TNF-alpha and
      conversely increased that of IL-10 upon stimulation with LPS. In accordance with
      this change of cytokine production, DCs treated with ANP plus LPS promoted
      differentiation of naive CD4(+) T cells into a Th2 phenotype. Finally, we
      presented evidence that ANP affected cytokine production of fresh whole blood
      stimulated with LPS in line with the above-mentioned results. These results
      indicate that ANP polarizes human DCs toward a Th2-promoting phenotype through GC
      A and thus can regulate immune responses.

PMID- 12794113
TI  - Differential regulation of killer cell lectin-like receptor G1 expression on T
      cells.
AB  - The killer cell lectin-like receptor G1 (KLRG1) is the mouse homologue of the rat
      mast cell function-associated Ag and contains a tyrosine-based inhibitory motif
      in its cytoplasmic domain. It has been demonstrated that KLRG1 is induced on
      activated NK cells and that KLRG1 can inhibit NK cell effector functions. In this
      study, we show that in naive C57BL/6 mice KLRG1 is expressed on a subset of
      CD44(high)CD62L(low) T cells. KLRG1 expression can be detected on a small number
      of V(alpha)14i NK T cells but not on CD8alphaalpha(+) intraepithelial T cells
      that are either TCRgammadelta(+) or TCRalphabeta(+). We also show that KLRG1
      expression is dramatically induced on approximately 50% of the CD8(+) T cells
      during both a viral and a parasitic infection. Interestingly, during Toxoplasma
      gondii infection, KLRG1 is up-regulated on CD4(+) T cells. Although KLRG1
      expression can be induced on both NK cells and T cells, the molecular mechanism
      leading to the induction of KLRG1 differs in these two subsets of cells. Indeed,
      the up-regulation of KLRG1 on NK cells can be driven in vivo by cytokines,
      whereas KLRG1 cannot be induced on CD8(+) T cells by cytokines. In addition,
      although induction of KLRG1 on T cells appears to require TCR engagement in vivo,
      TCR engagement is not sufficient for KLRG1 induction in vitro. Taken together,
      these data suggest that the expression and induction of KLRG1 on T cells are
      tightly regulated. This could have important biological consequences on T cell
      activation and homeostasis.

PMID- 12794114
TI  - Aod1 controlling day 3 thymectomy-induced autoimmune ovarian dysgenesis in mice
      encompasses two linked quantitative trait loci with opposing allelic effects on
      disease susceptibility.
AB  - Day 3 thymectomy (D3Tx) leads to a paucity of CD4(+)CD25(+) suppressor T cells, a
      loss of peripheral tolerance, and the development of organ-specific autoimmune
      disease in adult mice. Importantly, D3Tx does not lead to autoimmune disease in
      all mouse strains, indicating that this process is genetically controlled.
      Previously, we reported linkage of D3Tx-induced autoimmune ovarian dysgenesis
      (AOD) and its intermediate phenotypes, antiovarian autoantibody responsiveness,
      oophoritis, and atrophy, to five quantitative trait loci (QTL), designated Aod1
      through Aod5. We also showed interaction between these QTL and H2 as well as
      Gasa2, a QTL controlling susceptibility to D3Tx-induced autoimmune gastritis. To
      physically map Aod1, interval-specific bidirectional recombinant congenic strains
      of mice were generated and studied for susceptibility to D3Tx-induced AOD.
      Congenic mapping studies revealed that Aod1 controls susceptibility to oophoritis
      and comprises two linked QTL with opposing allelic effects. Aod1a resides between
      D16Mit211 (23.3 cM) and D16Mit51 (66.75 cM) on chromosome 16. Aod1b maps proximal
      of Aod1a between D16Mit89 (20.9 cM) and D16Mit211 (23.3 cM) and includes the
      candidate genes stefin A1, A2, and A3 (Stfa1-Stfa3), inhibitors of cathepsin S, a
      cysteine protease required for autoantigen presentation, and the development of
      autoimmune disease of the salivary and lacrimal glands following D3Tx. cDNA
      sequencing revealed the existence of structural polymorphisms for both Stfa1 and
      Stfa2. Given the roles of cathepsins in Ag processing and presentation, Stfa1 and
      Stfa2 alleles have the potential to control susceptibility to autoimmune disease
      at the level of both CD4(+)CD25(+) suppressor and CD4(+)CD25(-) effector T cells.

PMID- 12794115
TI  - Transfection of dendritic cells with RNA induces CD4- and CD8-mediated T cell
      immunity against breast carcinomas and reveals the immunodominance of presented T
      cell epitopes.
AB  - Transfection of dendritic cells (DC) with tumor-derived RNA has recently been
      shown to elicit tumor-specific CTL capable of recognizing and lysing a variety of
      tumor cells. In our study we analyzed the induction of HLA class I- and II
      restricted T cell responses against MCF-7 breast cancer cells. Using this
      approach we were able to elicit CD4- and CD8-mediated antitumor responses. The
      CTL specifically lysed MCF-7 cells and DC electroporated with MCF-7 RNA, but
      spared control cell lines. The specificity of the cytotoxic activity was
      confirmed in cold target inhibition assays and using mAbs blocking HLA class I
      molecules. Interestingly, these polyclonal cytotoxic T cells recognized
      selectively two epitopes derived from the MUC1 and Her-2/neu tumor Ags. The
      induced Th cells were found to be entirely HLA class II restricted and showed a
      significant cross-reactivity to a renal cell carcinoma cell line, similar to the
      results obtained with cytotoxic T cells.

PMID- 12794117
TI  - Paxillin binding to the alpha 4 integrin subunit stimulates LFA-1 (integrin alpha
      L beta 2)-dependent T cell migration by augmenting the activation of focal
      adhesion kinase/proline-rich tyrosine kinase-2.
AB  - Engagement of very late Ag-4 (integrin alpha(4)beta(1)) by ligands such as VCAM-1
      markedly stimulates leukocyte migration mediated by LFA-1 (integrin
      alpha(L)beta(2)). This form of integrin trans-regulation in T cells requires the
      binding of paxillin to the alpha(4) integrin cytoplasmic domain. This conclusion
      is based on the abolition of trans-regulation in Jurkat T cells by an alpha(4)
      mutation (alpha(4)(Y991A)) that disrupts paxillin binding. Furthermore, cellular
      expression of an alpha(4)-binding fragment of paxillin that blocks the alpha(4)
      paxillin interaction, selectively blocked VCAM-1 stimulation of alpha(L)beta(2)
      dependent cell migration. The alpha(4)-paxillin association mediates trans
      regulation by enhancing the activation of tyrosine kinases, focal adhesion kinase
      (FAK) and/or proline-rich tyrosine kinase-2 (Pyk2), based on two lines of
      evidence. First, disruption of the paxillin-binding site in the alpha(4) tail
      resulted in much less alpha(4)beta(1)-mediated phosphorylation of Pyk2 and FAK.
      Second, transfection with cDNAs encoding C-terminal fragments of Pyk2 and FAK,
      which block the function of the intact kinases, blocked alpha(4)beta(1)
      stimulation of alpha(L)beta(2)-dependent migration. These results define a
      proximal protein-protein interaction of an integrin cytoplasmic domain required
      for trans-regulation between integrins, and establish that augmented activation
      of Pyk2 and/or FAK is an immediate signaling event required for the trans
      regulation of integrin alpha(L)beta(2) by alpha(4)beta(1).

PMID- 12794116
TI  - B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40
      antibody, induce anergy in CD8+ T cells: role of TGF-beta 1.
AB  - B cells recognize Ag through their surface IgRs and present it in the context of
      MHC class II molecules to CD4(+) T cells. Recent evidence indicates that B cells
      also present exogenous Ags in the context of MHC class I to CD8(+) T cells and
      thus may play an important role in the modulation of CTL responses. However, in
      this regard, conflicting reports are available. One group of studies suggests
      that the interaction between B cells and CD8(+) T cells leads to the activation
      of the T cells, whereas other studies propose that it induces T cell tolerance.
      For discerning this dichotomy, we used B cells that were activated with either
      LPS or anti-Ig plus anti-CD40 Ab, which mimic the T-independent and T-dependent
      modes of B cell activation, respectively, to provide accessory signals to resting
      CD8(+) T cells. Our results show that, in comparison with anti-Ig plus anti-CD40
      Ab-activated B cells, the LPS-activated B cells (LPS-B) failed to induce
      significant levels of proliferation, cytokine secretion, and cytotoxic ability of
      CD8(+) T cells. This hyporesponsiveness of CD8(+) T cells activated with LPS-B
      was significantly rescued by anti-TGF-beta1 Ab. Moreover, it was found that such
      hyporesponsive CD8(+) T cells activated with LPS-B had entered a state of anergy.
      Furthermore, LPS-B expresses a significantly higher level of TGF-beta1 on the
      surface, which caused the observed hyporesponsiveness of CD8(+) T cells.
      Therefore, this study, for the first time, provides a novel mechanism of B cell
      surface TGF-beta1-mediated hyporesponsiveness leading to anergy of CD8(+) T
      cells.

PMID- 12794118
TI  - Potentiation of a tumor cell susceptibility to autologous CTL killing by
      restoration of wild-type p53 function.
AB  - Inactivation of p53 has been implicated in many types of tumors particularly in
      non-small cell lung carcinoma, one of the most common cancers in which p53
      mutation has been frequently identified. The aim of this study was to investigate
      the influence of p53 status on the regulation of tumor susceptibility to specific
      CTL-mediated cell death. For this purpose, we used a cytotoxic T lymphocyte
      clone, Heu127, able to lyse the human autologous lung carcinoma cell line, IGR
      Heu, in a HLA-A2-restricted manner. Direct genomic DNA sequencing revealed that
      IGR-Heu expresses a mutated p53 at codon 132 of the exon 5 which results in the
      loss of p53 capacity to induce the expression of the p53-regulated gene product
      p21(waf/CIP1). Initial experiments demonstrated that IGR-Heu was resistant to
      Fas, TNF, and TRAIL apoptotic pathways. This correlated with the lack of p55
      TNFRI, Fas, DR4, and DR5 expression. The effect of wild-type (wt) p53 restoration
      on the sensitization of IGR-Heu to autologous CTL clone lysis was investigated
      following infection of the tumor cell line with a recombinant adenovirus encoding
      the wt p53 (Adwtp53). We demonstrate that the restoration of wt p53 expression
      and function resulted in a significant potentiation of target cell susceptibility
      to CTL-mediated lysis. The wt p53-induced optimization of tumor cell killing by
      specific CTL involves at least in part Fas-mediated pathway via induction of CD95
      expression by tumor cells but does not appear to interfere with granzyme B
      cytotoxic pathway.

PMID- 12794119
TI  - Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC)
      suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8
      alpha- DC in the mouse.
AB  - Dendritic cells (DC) are the professional APCs that initiate T cell immune
      responses. DC can develop from both myeloid and lymphoid progenitors. In the
      mouse, the CD8alpha(+) DC had been designated as "lymphoid" DC, and CD8alpha(-)
      DC as "myeloid" DC until recently when it was demonstrated that common myeloid
      progenitors can also give rise to CD8alpha(+) DC in bone marrow chimera mice.
      However, it is still not clear which committed myeloid lineages differentiate
      into CD8alpha(+) DC. Because monocytes can differentiate into DC in vivo, the
      simplest hypothesis is that the CD8alpha(+) DC can be derived from the
      monocyte/macrophage. In this study we show that cell clones, isolated from
      CD8alpha(+) DC lymphoma but with a monocytic phenotype (CD11c(low/
      )D11b(high)CD8alpha(-)I-A(low)), can redifferentiate into CD8alpha(+) DC either
      when stimulated by LPS and CD40L or when they migrate into the lymphoid organs.
      Maturation of DC in vivo correlated with strong priming of allogeneic T cells.
      Moreover, the monocytes from cultured splenocytes or peritoneal exudates
      macrophages of wild-type mice are also capable of differentiating into
      CD11c(+)CD8alpha(+) DC after their migration into the draining lymph nodes. Our
      results suggest that monocytes can be direct precursors for CD11c(+)CD8alpha(+)
      DC in vivo. In addition, the monocyte clones described in this study may be
      valuable for studying the differentiation and function of CD8alpha(+) DC that
      mediate cross-presentation of Ag to CD8 T cells specific for cell-associate Ags.

PMID- 12794120
TI  - Pathogenesis of autoimmunity after xenogeneic thymus transplantation.
AB  - Thymus transplantation is a promising strategy to induce xenotolerance, but may
      also induce an autoimmune syndrome (AIS). The pathogenesis of this AIS was
      explored using nude rats as recipients. Thymus grafts consisted of fetal hamster
      thymic tissue with or without mixing with fetal rat tissue such as thymus,
      thyroid, salivary gland, and heart. All hamster thymus recipients died of AIS
      within 2-3 mo. In most recipients of xenothymus mixed with rat tissues such as
      thymus, thyroid, and salivary gland, but not heart, AIS was prevented, indicating
      an insufficient presence of rat epithelial cell Ags within the xenothymus. AIS
      could be transferred to control nude rats by whole splenocytes or by splenocyte
      subpopulations such as CD3(+), CD3(-), and B lymphocytes, but not by non-T, non-B
      cells from AIS animals. This transfer could be suppressed by cotransferring
      either CD4(+) or CD8(+) lymphocytes from euthymic rats, but not by splenocytes
      from recipients of syngeneic or xenogeneic thymus mixed with rat tissue,
      indicating a defective generation of regulatory lymphocytes. As for CD4(+)
      regulatory cells this defect was probably qualitative, because the percentages of
      CD4(+)CD25(+) or CD4(+)CD45RC(low) populations were normal after xenothymus
      transplantation. As for the CD8(+) regulatory cells, the defect was quantitative,
      as CD8(+) cell levels always remained low. The latter was related to the
      nonvascularized nature of thymus grafts. In conclusion, AIS after xenothymus
      transplantation in nude rats is due to a combination of insufficient intrathymic
      presence of host-type epithelial cell Ags and a defective generation of
      regulatory T lymphocytes.

PMID- 12794121
TI  - TCR dynamics in human mature T lymphocytes lacking CD3 gamma.
AB  - The contribution of CD3gamma to the surface expression, internalization, and
      intracellular trafficking of the TCR/CD3 complex (TCR) has not been completely
      defined. However, CD3gamma is believed to be crucial for constitutive as well as
      for phorbol ester-induced internalization. We have explored TCR dynamics in
      resting and stimulated mature T lymphocytes derived from two unrelated human
      congenital CD3gamma-deficient (gamma(-)) individuals. In contrast to gamma(-)
      mutants of the human T cell line Jurkat, which were selected for their lack of
      membrane TCR and are therefore constitutively surface TCR negative, these natural
      gamma(-) T cells constitutively expressed surface TCR, mainly through
      biosynthesis of new chains other than CD3gamma. However, surface (but not
      intracellular) TCR expression in these cells was less than wild-type cells, and
      normal surface expression was clearly CD3gamma-dependent, as it was restored by
      retroviral transduction of CD3gamma. The reduced surface TCR expression was
      likely caused by an impaired assembly or membrane transport step during
      recycling, whereas constitutive internalization and degradation were apparently
      normal. Ab binding to the mutant TCR, but not phorbol ester treatment, caused its
      down-modulation from the cell surface, albeit at a slower rate than in normal
      controls. Kinetic confocal analysis indicated that early ligand-induced
      endocytosis was impaired. After its complete down-modulation, TCR re-expression
      was also delayed. The results suggest that CD3gamma contributes to, but is not
      absolutely required for, the regulation of TCR trafficking in resting and Ag
      stimulated mature T lymphocytes. The results also indicate that TCR
      internalization is regulated differently in each case.

PMID- 12794122
TI  - Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial
      cells.
AB  - Lipopolysaccharide (endotoxin) tolerance is well described in monocytes and
      macrophages, but is less well characterized in endothelial cells. Because
      intestinal microvascular endothelial cells exhibit a strong immune response to
      LPS challenge and play a critical regulatory role in gut inflammation, we sought
      to characterize the activation response of these cells to repeated LPS exposure.
      Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were
      stimulated with LPS over 6-60 h and activation was assessed using U937 leukocyte
      adhesion, expression of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, manganese
      superoxide dismutase, HLA-DR, and CD86. Effect of repeat LPS stimulation on HIMEC
      NF-kappaB and mitogen-activated protein kinase (MAPK) activation, generation of
      superoxide anion, and Toll-like receptor 4 expression was characterized. LPS
      pretreatment of HIMEC for 24-48 h significantly decreased leukocyte adhesion
      after subsequent LPS stimulation. LPS pretreatment inhibited expression of E
      selectin, VCAM-1, IL-6, and CD86, while ICAM-1, IL-8, and HLA-DR were not
      altered. Manganese superoxide dismutase expression increased with repeated LPS
      stimulation, with a reduction in intracellular superoxide. NF-kappaB activation
      was transiently inhibited by LPS pretreatment for 6 h, but not at later time
      points. In contrast, p44/42 MAPK, p38 MAPK, and c-Jun N-terminal kinase
      activation demonstrated inhibition by LPS pretreatment 24 or 48 h prior. Toll
      like receptor 4 expression on HIMEC was not altered by LPS. HIMEC exhibit
      endotoxin tolerance after repeat LPS exposure in vitro, characterized by
      diminished activation and intracellular superoxide anion concentration, and
      reduced leukocyte adhesion. HIMEC possess specific mechanisms of immunoregulatory
      hyporesponsiveness to repeated LPS exposure.

PMID- 12794123
TI  - Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function.
AB  - HIV infection leads to numerous immunologic defects, including impaired B cell
      function. An effective humoral response requires bidirectional interactions
      between B cells and CD4(+) T cells, critical of which are interactions between
      CD80/CD86 expressed on activated B cells and CD28 expressed on responder CD4(+) T
      cells. In the present study, we examined the effect of active HIV replication on
      B cell costimulatory function. Induction of CD80/CD86 on B cells following B cell
      receptor and CD40 triggering and responsiveness of CD4(+) T cells to activated B
      cells were investigated in a system where B cells of HIV-infected patients were
      compared concurrently to B cells of HIV-negative donors. In contrast to HIV
      aviremic patients, B cells of HIV-viremic patients were ineffective at
      stimulating CD4(+) T cells, as measured by the induction of activation markers
      and proliferation. The importance of interactions of CD80/CD86 and CD28 in
      activating CD4(+) T cells was clear; the ablation of a normal response following
      the addition of neutralizing anti-CD86/CD80 Abs mirrored the response of CD4(+) T
      cells to B cells of HIV-viremic patients, while the addition of exogenous CD28
      ligands partially restored the poor CD4(+) T cell response to the B cells of HIV
      viremic patients. Ineffective B cell costimulatory function in HIV-viremic
      patients was associated with low induction of CD80/CD86 expression on B cells.
      Our findings further delineate the scope of defects associated with cognate B
      cell-CD4(+) T cell interactions in HIV infection and suggest that therapeutic
      interventions designed to enhance CD28-dependent costimulatory pathways may help
      restore immune functions.

PMID- 12794124
TI  - Alterations in Fas expression are characteristic of, but not solely responsible
      for, enhanced metastatic competence.
AB  - Dysregulation of the Fas pathway has been implicated in tumor progression;
      however, how alterations in Fas expression influence metastatic behavior remains
      unresolved. In this study, we investigated the link between Fas expression and
      metastatic capacity in two mouse tumor models: one was a sarcoma, which was used
      to analyze the consequences of loss of Fas function in experimental pulmonary
      metastases, and the other was a mammary carcinoma, where Fas expression was
      examined in matched pairs of primary and metastatic cell lines as well as by
      immunohistochemistry of tissues taken from primary and metastatic sites of
      spontaneous tumor development. In the sarcoma model, a Fas-resistant/refractory
      subline was produced in vitro from the parental line by biologic selection
      against Fas-responsive cells, and it was then compared with the poorly metastatic
      parental line and to an in vivo-derived subline that was highly metastatic for
      growth in the lungs. In both tumor models, an inverse correlation was
      demonstrated between Fas expression and metastatic phenotype. Subsequent studies
      in the sarcoma model revealed that although the Fas-resistant/refractory subline
      displayed significant metastatic ability, the parental line from which it was
      derived exhibited little to no additional metastatic activity if experimentally
      rendered Fas-resistant by molecular-based strategies or transplanted into a Fas
      ligand-deficient host. Therefore, these findings suggested that down-regulation
      of Fas was associated with the metastatic phenotype, but alterations in Fas
      expression alone were insufficient for acquisition of full metastatic potential.
      Rather, the ability of such Fas-resistant neoplastic subpopulations to achieve
      metastatic competence apparently required co-possession of additional malignant
      characteristics.

PMID- 12794125
TI  - A model for antigen-specific T-cell anergy: displacement of CD4-p56(lck)
      signalosome from the lipid rafts by a soluble, dimeric peptide-MHC class II
      chimera.
AB  - Soluble, dimeric peptide-MHC chimeras were shown to induce Ag-specific T cell
      anergy in vitro and in vivo. In this study, we describe a mechanism by which a
      soluble, dimeric peptide MHC class II chimera (DEF) induces Ag-specific T cell
      anergy. The anergic cells showed a displacement of the CD4-p56(lck) signaling
      module from the GM1-rich plasma membrane microdomains (lipid rafts), and
      subsequently an increase in p59(fyn) kinase activity, a dominant expression of
      p21 inhibitory TCR zeta-chain, and a poor phosphorylation and recruitment of zeta
      associated protein of 70 kDa kinase to the TCR's immunoreceptor tyrosine-based
      activation motifs. The Th1 and Th2 transcription was suppressed and the cells
      were arrested in the Th0 stage of differentiation. Recovery from DEF anergy
      occurred late and spontaneously at the expense of low thresholds for activation
      induced cell death. In contrast to DEF, a combination of TCR and CD4 mAbs did not
      induce such alterations or anergy, indicating that the ligand-mediated topology
      of TCR and CD4 coengagement can differentially affect the T cell function. Our
      results argue for a model of anergy in which the defective partitioning of
      signaling molecules in lipid rafts is an early, negative signaling event in T
      cells. Physiological ligands like DEF chimeras may provide new tools for
      silencing the autoimmune processes, and may also help in deciphering new
      mechanisms of negative regulation in T cells.

PMID- 12794126
TI  - Acquisition of viral receptor by NK cells through immunological synapse.
AB  - Occasional EBV infection of human NK cells may lead to malignant diseases such as
      naso-pharyngeal NK lymphoma although NK cells do not express CD21, the primary
      receptor for EBV. Here we show that during early EBV infection in patients, NK
      cells attacked EBV-infected autologous B cells. In vitro, NK cells activated by
      conjugation to CD21(+) B-EBV cell targets transiently acquired a weak CD21(+)
      phenotype by synaptic transfer of few receptor molecules onto their own membrane.
      In the presence of viral particles, these ectopic receptors allowed EBV binding
      to the novel NK cell host. Hence, trans-synaptic acquisition of viral receptor
      from target cells might constitute an unsuspected mode of infection for otherwise
      unreachable lymphoid hosts.

PMID- 12794127
TI  - IL-1 beta scavenging by the type II IL-1 decoy receptor in human neutrophils.
AB  - IL-1 elicits its cellular effects by binding a heterodimeric receptor consisting
      of IL-1RI and the accessory protein, IL-1RAcPr. In addition, it binds to IL-1RII,
      which lacking signaling function has been ascribed a decoy role. The fate of the
      ligand following interaction with the decoy receptor was examined in human
      polymorphonuclear cells (PMN), which express predominantly (>90%) IL-1RII.
      Incubation of PMN with IL-1beta results in a rapid decrease in cell surface
      associated ligand accompanied by a concomitant increase in internalized IL-1 with
      50-60% of IL-1beta located intracellularly within 1 h at 37 degrees C. The use of
      blocking Abs revealed that IL-1 internalization is mediated exclusively by the
      decoy receptor. The results of inhibitor analysis demonstrate that
      internalization requires ATP synthesis and involves clathrin-mediated
      endocytosis. Following removal of the ligand, the receptor was rapidly re
      expressed on the cell surface. Cyclohexamide, a protein synthesis inhibitor, had
      no effect upon the process, suggesting that the re-expressed receptor was
      recycled. In addition, human keratinocytes stably transfected with IL-1RII (HaCAT
      811) also internalized the IL-1RII with 43% cell surface receptor internalized
      after 90 min. Immunofluorescence microscopy revealed colocalization of the
      internalized receptor with wheat germ agglutinin-labeled internalized
      glycoproteins and early endosome Ag-1, a protein associated with the early
      endosome compartments, indicative of cellular uptake of IL-1RII by endocytosis.
      In contrast, little or no internalization was observed in other cells of immune
      origin. These results suggest that the decoy receptor IL-1RII can act as a
      scavenger of IL-1, representing a novel autoregulatory mechanism of the IL-1
      system.

PMID- 12794128
TI  - Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward
      the apoptotic-prone phenotype: homeostatic mechanisms of HIV protease inhibitors.
AB  - A decrease of mitochondrial membrane potential has been hypothesized to be a
      marker of apoptotic cells, including activated T lymphocytes. It was recently
      demonstrated that HIV protease inhibitors, independently from any viral
      infection, can hinder lymphocyte apoptosis by influencing mitochondrial
      homeostasis. To analyze the mechanisms underlying these effects, a specific study
      was undertaken in both resting and activated human PBL exposed to either receptor
      (e.g., anti-Fas)- or nonreceptor (e.g., radiation)-mediated apoptotic stimuli. T
      cell activation was found to be accompanied by a significant increase in
      mitochondrial membrane potential, or hyperpolarization, which was undetectable in
      resting cells. We also detected apoptotic hindering by HIV protease inhibitors
      only in activated T lymphocytes. This was apparently due to the ability of these
      drugs to block activation-associated mitochondria hyperpolarization, which, in
      turn, was paralleled by an impairment of cell cycle progression. Remarkably,
      protease inhibitors also prevented zidovudine-mediated mitochondrial toxicity.
      Finally, HIV-infected cells from naive patients behaved identically to activated
      T cells, displaying hyperpolarized mitochondria, while lymphocytes from patients
      under highly active antiretroviral therapy (which included HIV protease
      inhibitors) seemed to react as resting cells. Altogether these results clearly
      indicate that the hyperpolarization state of mitochondria may represent a
      prerequisite for the sensitization of lymphocytes to the so-called activation
      induced cell death. They also suggest that HIV protease inhibitors, by
      interfering with induction of the mitochondrial hyperpolarization state, can
      result in cell survival even independent of any viral infection.

PMID- 12794129
TI  - J chain in the nurse shark: implications for function in a lower vertebrate.
AB  - J chain is a small polypeptide covalently attached to polymeric IgA and IgM. In
      humans and mice, it plays a role in binding Ig to the polymeric Ig receptor for
      transport into secretions. The putative orthologue of mammalian J chain has been
      identified in the nurse shark by sequence analysis of cDNA and the polypeptide
      isolated from IgM. Conservation with J chains from other species is relatively
      poor, especially in the carboxyl-terminal portion, and, unlike other J chains,
      the shark protein is not acidic. The only highly conserved segment in all known J
      chains is a block of residues surrounding an N-linked glycosylation site. Of the
      eight half-cystine residues that are conserved in mammalian J chains, three are
      lacking in the nurse shark, including two in the carboxyl-terminal segment that
      have been reported to be required for binding of human J chain-containing IgA to
      secretory component. Taken together with these data, the relative abundance of J
      chain transcripts in the spleen and their absence in the spiral valve (intestine)
      suggest that J chain in nurse sharks may not have a role in Ig secretion.
      Analysis of J chain sequences in diverse species is in agreement with accepted
      phylogenetic relationships, with the exception of the earthworm, suggesting that
      the reported presence of J chain in invertebrates should be reassessed.

PMID- 12794130
TI  - Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T
      cells.
AB  - Eph receptor tyrosine kinases are expressed by T lineage cells, and stimulation
      with their ligands, the ephrins, has recently been shown to modulate T cell
      behavior. We show that ephrin-A1 stimulation of Jurkat T cells induces tyrosine
      phosphorylation of EphA3 receptors and cytoplasmic proteins, including the c-cbl
      proto-oncogene. Cbl phosphorylation was also observed in peripheral blood T
      cells. In contrast, stimulation of Jurkat cells with the EphB receptor ligand
      ephrin-B1 does not cause Cbl phosphorylation. EphA activation also induced Cbl
      association with Crk-L and Crk-II adapters, but not the related Grb2 protein.
      Induction of Cbl phosphorylation upon EphA activation appeared to be dependent
      upon Src family kinase activity, as Cbl phosphorylation was selectively abrogated
      by the Src family inhibitor 4-amino-5(4-chlorophenyl-7-(tert-butyl)pyrazolo[3,4
      d]pyrimidine, while EphA phosphorylation was unimpaired. Ephrin-A1 stimulation of
      Jurkat cells was also found to cause down-regulation of endogenous EphA3
      receptors from the cell surface and their degradation. In accordance with the
      role of Cbl as a negative regulator of receptor tyrosine kinases, overexpression
      of wild-type Cbl, but not its 70-Z mutant, was found to down-regulate EphA
      receptor expression. Receptor down-regulation could also be inhibited by blockage
      of Src family kinase activity. Our findings show that EphA receptors can actively
      signal in T cells, and that Cbl performs multiple roles in this signaling
      pathway, functioning to transduce signals from the receptors as well as
      regulating activated EphA receptor expression.

PMID- 12794131
TI  - Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in
      inhibition of mitogen-activated protein kinase and nuclear factor activation.
AB  - Polyunsaturated fatty acids (PUFAs) are known to suppress inflammatory and
      autoimmune responses and, therefore, clinical applications of PUFAs as
      immunomodulatory substances are extensively studied. PUFAs are known to inhibit T
      cell responses, but with respect to TCR/CD3-mediated signal transduction only a
      block in CD3-induced phospholipase Cgamma1/calcium signaling has been shown so
      far. In this study, we investigated PUFA-mediated changes in downstream T cell
      signal transduction. We show that among the mitogen-activated protein kinase
      families activation of c-Jun NH(2)-terminal kinase, but not phosphorylation of
      extracellular signal-regulated kinase-1/-2 or p38 is inhibited. CD3/CD28-induced
      activity of NF-AT was markedly reduced by PUFA treatment, while activation of
      other nuclear receptors (AP-1 and NF-kappaB) remained unaltered. Furthermore, IL
      2 promoter activity, IL-2 and IL-13 mRNA levels, IL-2 secretion, and IL-2R alpha
      chain expression were significantly diminished by PUFA treatment, whereas the
      expression of IFN-gamma, IL-4, IL-10, and CD69 remained essentially unaffected by
      PUFAs. In conclusion, PUFA treatment of T cells inhibits selectively c-Jun NH(2)
      terminal kinase and NF-AT activation, resulting in diminished production of IL-2
      and IL-13.

PMID- 12794132
TI  - Immunologically induced, complement-dependent up-regulation of the prion protein
      in the mouse spleen: follicular dendritic cells versus capsule and trabeculae.
AB  - The expression of the prion protein (PrP) in the follicular dendritic cell
      network of germinal centers in the spleen is critical for the splenic propagation
      of the causative agent of prion diseases. However, a physiological role of the
      prion protein in the periphery remains elusive. To investigate the role and
      function of PrP expression in the lymphoid system we treated naive mice i.v. with
      preformed immune complexes or vesicular stomatitis virus. Immunohistochemistry
      and Western blot analysis of the spleen revealed that 8 days after immunization,
      immune complexes and vesicular stomatitis virus had both induced a strong
      increase of PrP expression in the follicular dendritic cell network. Remarkably,
      this up-regulation did not occur in mice that lack an early factor of the
      complement cascade, C1q, a component which has been shown previously to
      facilitate early prion pathogenesis. In addition to the variable PrP level in the
      germinal centers, we detected steady and abundant PrP expression in the splenic
      capsule and trabeculae, which are structural elements that have not been
      associated before with PrP localization. The abundant trabeculo-capsular PrP
      expression was also evident in spleens of Rag-1-deficient mice, which have been
      shown before to be incapable of prion expansion. We conclude that
      trabeculocapsular PrP is not sufficient for splenic prion propagation.
      Furthermore, our observations may provide important clues for a physiological
      function of the prion protein and allow a new view on the role of complement and
      PrP in peripheral prion pathogenesis.

PMID- 12794133
TI  - Hepatocyte NF-1 and STAT6 cooperate with additional DNA-binding factors to
      activate transcription of the human polymeric Ig receptor gene in response to IL
      4.
AB  - Secretory IgA and IgM, which protect the mucosal surfaces, are generated by
      selective transport of locally produced polymeric (p)Igs through the epithelial
      barrier by the pIgR. The expression of this receptor, and hence the generation of
      secretory Igs, is modulated by numerous extracellular factors. We have previously
      identified a STAT6 site in intron 1 of the human pIgR gene that is required for
      the slow and de novo protein synthesis-dependent IL-4-mediated transcriptional
      activation of the gene. In this study, we show that this intronic IL-4-responsive
      enhancer is confined to a 250-bp region that is highly conserved in the murine
      pIgR gene. The enhancer was dependent on the cooperation between the STAT6 site
      and at least four additional DNA elements. EMSA experiments demonstrated binding
      by hepatocyte NF-1 to one of these DNA elements. Extensive overlap in the tissue
      distribution of hepatocyte NF-1 and pIgR suggests that this transcription factor
      contributes to tissue-specific pIgR expression. Changing the helical phase
      between the STAT6 site and downstream DNA elements greatly reduced the strength
      of the IL-4 response, suggesting that the precise organization of this enhancer
      is important for its proper function. Thus, several transcription factors
      cooperate in this enhanceosome to mediate IL-4 responsiveness in HT-29 epithelial
      cells.

PMID- 12794134
TI  - Characterization and analysis of the proximal Janus kinase 3 promoter.
AB  - Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling
      via cytokine receptors that comprise the common gamma-chain (gammac), i.e., the
      receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is preferentially
      expressed in hemopoietic cells and is up-regulated upon cell differentiation and
      activation. Despite the importance of Jak3 in lymphoid development and immune
      function, the mechanisms that govern its expression have not been defined. To
      gain insight into this issue, we set out to characterize the Jak3 promoter. The
      5'-untranslated region of the Jak3 gene is interrupted by a 3515-bp intron.
      Upstream of this intron and the transcription initiation site, we identified an
      approximately 1-kb segment that exhibited lymphoid-specific promoter activity and
      was responsive to TCR signals. Truncation of this fragment revealed that core
      promoter activity resided in a 267-bp fragment that contains putative Sp-1, AP-1,
      Ets, Stat, and other binding sites. Mutation of the AP-1 sites significantly
      diminished, whereas mutation of the Ets sites abolished, the inducibility of the
      promoter construct. Chromatin immunoprecipitation assays showed that histone
      acetylation correlates with mRNA expression and that Ets-1/2 binds this region.
      Thus, transcription factors that bind these sites, especially Ets family members,
      are likely to be important regulators of Jak3 expression.

PMID- 12794135
TI  - Caspase activity is required for stimulated B lymphocytes to enter the cell
      cycle.
AB  - Following activation with proliferative stimuli, including ligation of CD40,
      dense human tonsillar B cells (>98% cells in G(0)) have increased cleavage and
      activation of caspase-8 and -6 accompanied by decreased caspase-3 activation and
      apoptosis. Proliferation was blocked by either a broad specificity caspase
      inhibitor or inhibitors selective for caspase-6 or caspase-8. In contrast, an
      inhibitor selective for caspase-3 was without effect. Furthermore, induction of
      cyclin D and cyclin-dependent kinase 4 mRNA and protein was blocked upon
      inhibition of caspase-6, but not caspase-3. Thus, caspase-6-like activity is
      required for quiescent B cells to increase the expression of genes required for
      entry into G(1). In support of this model, the transcriptional suppressor special
      AT-rich sequence-binding protein 1, a preferred caspase-6 substrate, was cleaved
      upon B cell stimulation. Caspase activity was not required for all signaling
      events, as caspase inhibitors did not affect the phosphorylation of p42/44
      mitogen-activated protein kinase, the expression of the survival factor cellular
      inhibitor of apoptosis 2, or the production of IL-6 by stimulated G(0) B cells.
      These findings suggest a mechanism by which caspase-6 may selectively allow entry
      of quiescent B cells into the cell cycle.

PMID- 12794136
TI  - Different and divergent regulation of the KIR2DL4 and KIR3DL1 promoters.
AB  - The killer Ig-like receptors (KIR) are a family of highly related MHC class I
      receptors that show extreme genetic polymorphism both within the human population
      and between closely related primate species, suggestive of rapid evolutionary
      diversification. Most KIR are expressed in a variegated fashion by the NK
      population, giving rise to an NK repertoire of specificities for MHC class I. We
      compared the promoter for KIR3DL1, which exhibits variegated gene expression,
      with that for KIR2DL4, which is expressed by all NK cell clones. Maximum
      transcriptional activity of each was encoded within approximately 270 bp upstream
      of the translation initiation codon. The KIR2DL4 promoter drove reporter gene
      expression only in NK cells, while the KIR3DL1 promoter was active in a range of
      cell types, suggesting that the latter requires other regulatory elements for
      physiological expression. In NK cells, reporter gene expression driven by the
      KIR2DL4 promoter was greater than that driven by the KIR3DL1 promoter. DNase I
      footprinting revealed that transcription factor binding sites differ between the
      two promoters. The data indicate that while the promoters of these two KIR genes
      share 67% nucleotide identity, they have evolved distinct properties consistent
      with different roles in regulating the generation of NK repertoire.

PMID- 12794138
TI  - Biochemical features of the MHC-related protein 1 consistent with an
      immunological function.
AB  - MHC-related protein (MR)1 is an MHC class I-related molecule encoded on
      chromosome 1 that is highly conserved among mammals and is more closely related
      to classical class I molecules than are other nonclassical class I family
      members. In this report, we show for the first time that both mouse and human MR1
      molecules can associate with the peptide-loading complex and can be detected at
      low levels at the surface of transfected cells. We also report the production of
      recombinant human MR1 molecules in insect cells using highly supplemented media
      and provide evidence that the MR1 H chain can assume a folded conformation and is
      stoichiometrically associated with beta(2)-microglobulin, similar to class I
      molecules. Cumulatively, these findings demonstrate that surface expression of
      MR1 is possible but may be limited by a specific ligand or associated molecule.

PMID- 12794137
TI  - Functional epitope on human neutrophil flavocytochrome b558.
AB  - mAb NL7 was raised against purified flavocytochrome b(558), important in host
      defense and inflammation. NL7 recognized the gp91(phox) flavocytochrome b(558)
      subunit by immunoblot and bound to permeabilized neutrophils and neutrophil
      membranes. Epitope mapping by phage display analysis indicated that NL7 binds the
      (498)EKDVITGLK(506) region of gp91(phox). In a cell-free assay, NL7 inhibited in
      vitro activation of the NADPH oxidase in a concentration-dependent manner, and
      had marginal effects on the oxidase substrate Michaelis constant (K(m)). mAb NL7
      did not inhibit translocation of p47(phox), p67(phox), or Rac to the plasma
      membrane, and bound its epitope on gp91(phox) independently of cytosolic factor
      translocation. However, after assembly of the NADPH oxidase complex, mAb NL7
      bound the epitope but did not inhibit the generation of superoxide. Three
      dimensional modeling of the C-terminal domain of gp91(phox) on a corn nitrate
      reductase template suggests close proximity of the NL7 epitope to the proposed
      NADPH binding site, but significant separation from the proposed p47(phox)
      binding sites. We conclude that the (498)EKDVITGLK(506) segment resides on the
      cytosolic surface of gp91(phox) and represents a region important for oxidase
      function, but not substrate or cytosolic component binding.

PMID- 12794139
TI  - Polyvalent antigens stabilize B cell antigen receptor surface signaling
      microdomains.
AB  - The B cell Ag receptor (BCR) can distinguish subtle differences in Ag structure
      and trigger differential responses. In this study, we analyzed the effects of Ag
      valency on the signaling and Ag-targeting functions of the BCR. Although both
      paucivalent and polyvalent Ags induced the redistribution of the surface BCR into
      polarized caps, polyvalent Ag-induced BCR caps persisted. Ganglioside G(M1), a
      lipid raft marker, and tyrosine-phosphorylated proteins, but not CD45 and
      transferrin receptor, were concentrated in BCR caps, suggesting BCR caps as
      surface-signaling microdomains. Prolonged BCR caps were concomitant with an
      increase in the level and duration of protein tyrosine phosphorylation and a
      reduction in BCR internalization and movement to late endosomes/lysosomes. Thus,
      Ag valency influences B cell responses by modulating the stability of BCR
      signaling microdomains and BCR trafficking.

PMID- 12794140
TI  - Spontaneous clustering and tyrosine phosphorylation of NK cell inhibitory
      receptor induced by ligand binding.
AB  - Inhibition of NK cell cytotoxicity by killer cell Ig-like receptors (KIR) depends
      on phosphorylation of cytoplasmic tyrosines in KIR, which recruit tyrosine
      phosphatase Src homology protein tyrosine phosphatase 1. It is not clear how KIR,
      whose function lies downstream of a tyrosine kinase, succeeds in blocking
      proximal NK cell activation signals upon binding HLA class I on target cells.
      Here we show that mixing NK cells with insect cells expressing HLA-C was
      sufficient to induce clustering of KIR, and phosphorylation of KIR and SHP-1.
      Transient phosphorylation of KIR was detected in the presence of pervanadate, an
      inhibitor of protein tyrosine phosphatases, at suboptimal concentration.
      Phosphorylation of KIR was specifically induced by ligand binding because it was
      detected only when HLA-C was loaded with a peptide that permits KIR binding. KIR
      phosphorylation was not dependent on ICAM-1-mediated adhesion and was not blocked
      by inhibition of actin polymerization, but required Zn(2+). Fluorescence
      resonance energy transfer between HLA-C molecules revealed close molecular
      interactions induced by KIR binding. These results demonstrate tight clustering
      of KIR and rapid KIR phosphorylation induced simply by binding to HLA-C. The
      unique property of KIR to become phosphorylated in the absence of adhesion and of
      actin cytoskeleton rearrangement explains how KIR can efficiently block early
      activation signals during NK-target cell contacts.

PMID- 12794141
TI  - Structure-function relationships of human C5a and C5aR.
AB  - Using peptides that represent linear regions of the powerful complement
      activation product, C5a, or loops that connect the four alpha helices of C5a, we
      have defined the ability of these peptides to reduce binding of (125)I-C5a to
      human neutrophils, inhibit chemotactic responses of neutrophils to C5a, and
      reduce H(2)O(2) production in neutrophils stimulated with PMA. The data have
      defined likely sites of interaction of C5a with C5aR. The peptides had no
      functional activity per se on neutrophils and did not interfere with neutrophil
      responses to the unrelated chemotactic peptide, N-formyl-Met-Leu-Phe. Although
      previous data have suggested that there are two separate sites on C5a reactive
      with C5aR, the current data suggest that C5a interacts with C5aR in a manner that
      engages three discontinuous regions of C5a.

PMID- 12794142
TI  - OX40 ligation on activated T cells enhances the control of Cryptococcus
      neoformans and reduces pulmonary eosinophilia.
AB  - Pulmonary eosinophilia induced in C57BL/6 mice after Cryptococcus neoformans
      infection is driven by CD4(+) Th2 cells. The immunological mechanisms that
      protect against eosinophilia are not fully understood. Interaction of OX40
      (CD134) and its ligand, OX40L, has been implicated in T cell activation and cell
      migration. Unlike CD28, OX40 is only expressed on T cells 1-2 days after Ag
      activation. Manipulation of this pathway would therefore target recently
      activated T cells, leaving the naive repertoire unaffected. In this study, we
      show that engagement of OX40 by an OX40L:Ig fusion protein drives IFN-gamma
      production by CD4(+) T cells and reduces eosinophilia and C. neoformans burden in
      the lung. Using gene-depleted mice, we show that reduction of eosinophilia and
      pathogen burden requires IL-12 and/or IFN-gamma. C. neoformans infection itself
      only partially induces OX40L expression by APCs. Provision of exogenous OX40L
      reveals a critical role of this pathway in the prevention of C. neoformans
      induced eosinophilia.

PMID- 12794143
TI  - Salmonella typhimurium strains carrying independent mutations display similar
      virulence phenotypes yet are controlled by distinct host defense mechanisms.
AB  - The outcome of Salmonella infection in the mammalian host favors whoever succeeds
      best in disturbing the equilibrium between coordinate expression of bacterial
      (virulence) genes and host defense mechanisms. Intracellular persistence in host
      cells is critical for pathogenesis and disease, because Salmonella typhimurium
      strains defective in this property are avirulent. We examined whether similar
      host defense mechanisms are required for growth control of two S. typhimurium
      mutant strains. Salmonella pathogenicity island 2 (SPI2) and virulence plasmid
      cured Salmonella mutants display similar virulence phenotypes in immunocompetent
      mice, yet their gene loci participate in independent virulence strategies. We
      determined the role of TNF-alpha and IFN-gamma as well as different T cell
      populations in infection with these Salmonella strains. After systemic infection,
      IFN-gamma was essential for growth restriction of plasmid-cured S. typhimurium,
      while SPI2 mutant infections were controlled in the absence of IFN-gamma. TNFRp55
      deficiency restored systemic virulence to both Salmonella mutants. After oral
      inoculation, control of plasmid-cured bacteria substantially relied on both IFN
      gamma and TNF-alpha signaling while control of SPI2 mutants did not. However, for
      both mutants, ultimate clearance of bacteria from infected mice depended on
      alphabeta T cells.

PMID- 12794145
TI  - The autoreactivity of anti-phosphorylcholine antibodies for atherosclerosis
      associated neo-antigens and apoptotic cells.
AB  - Abs specific for phosphorylcholine (PC) are known to contribute to the immune
      defense against a variety of microbial infections. To assess for other types of
      binding interactions, we performed surveys of anti-PC Abs of diverse biologic
      origins and structural diversity and demonstrated a common autoreactivity for
      oxidatively modified low density lipoprotein and other oxidation-specific
      structures containing PC-Ags. We also found that cells undergoing apoptosis
      sequentially express a range of oxidation-specific neo-self PC determinants.
      Whereas natural Abs to PC recognized cells at early stages of apoptosis, by
      contrast, an IgG anti-PC Ab, representative of a T cell-dependent response,
      recognized PC determinants primarily associated with late stages of apoptosis.
      Cumulatively, these results demonstrate a fundamental paradigm in which Abs from
      both the innate and the T cell-dependent tiers of the B cell compartment
      recognize a minimal molecular motif arrayed both on microbes and as neo-self Ags
      linked to atherosclerosis and autoimmune disease.

PMID- 12794144
TI  - Overexpression of Toll-like receptor 4 amplifies the host response to
      lipopolysaccharide and provides a survival advantage in transgenic mice.
AB  - Toll-like receptors are transmembrane proteins that are involved in the innate
      immune recognition of microbial constituents. Among them, Toll-like receptor 4
      (Tlr4) is a crucial signal transducer for LPS, the major component of Gram
      negative bacteria outer cell membrane. The contribution of Tlr4 to the host
      response to LPS and to infection with virulent Salmonella typhimurium was studied
      in four transgenic (Tg) strains including three overexpressing Tlr4. There was a
      good correlation between the level of Tlr4 mRNA expression and the sensitivity to
      LPS both in vitro and in vivo: Tg mice possessing the highest number of Tlr4
      copies respond the most to LPS. Overexpression of Tlr4 by itself appears to have
      a survival advantage in Tg mice early during infection: animals possessing more
      than two copies of the gene survived longer and in a greater percentage to
      Salmonella infection. The beneficial effect of Tlr4 overexpression is greatly
      enhanced when the mice present a wild-type allele at natural resistance
      associated macrophage protein 1, another critical innate immune gene involved in
      resistance to infection with Salmonella. Tlr4 and natural resistance-associated
      macrophage protein 1 exhibit functional epistatic interaction to improve the
      capacity of the host to control bacterial replication. However, this early
      improvement in disease resistance is not conducted later during infection,
      because mice overexpressing Tlr4 developed an excessive inflammatory response
      detrimental to the host.

PMID- 12794146
TI  - Central role of complement in passive protection by human IgG1 and IgG2 anti
      pneumococcal antibodies in mice.
AB  - Streptococcus pneumoniae is an important cause of morbitity and mortality
      worldwide. Capsule-specific IgG1 and IgG2 Abs are induced upon vaccination with
      polysaccharide-based vaccines that mediate host protection. We compared the
      protective capacity of human recombinant serogroup 6-specific IgG1 and IgG2 Abs
      in mice deficient for either leukocyte FcR or complement factors. Human IgG1 was
      found to interact with mouse leukocyte FcR in vitro, whereas human IgG2 did not.
      Both subclasses induced complement activation, resulting in C3c deposition on
      pneumococcal surfaces. Passive immunization of C57BL/6 mice with either subclass
      before intranasal challenge with serotype 6A induced similar degrees of
      protection. FcgammaRI- and III-deficient mice, as well as the combined FcgammaRI,
      II, and III knockout mice, were protected by passive immunization, indicating FcR
      not to be essential for protection. C1q or C2/factor B knockout mice, however,
      were not protected by passive immunization. Passively immunized C2/factor B(-/-)
      mice displayed higher bacteremic load than C1q(-/-) mice, supporting an important
      protective role of the alternative complement pathway. Spleens from wild-type and
      C1q(-/-) mice showed hyperemia and thrombotic vessel occlusion, as a result of
      septicemic shock. Notably, thrombus formation was absent in spleens of C2/factor
      B(-/-) mice, suggesting that the alternative complement pathway contributes to
      shock-induced intravascular coagulation. These studies demonstrate complement to
      play a central role in Ab-mediated protection against pneumococcal infection in
      vivo, as well as in bacteremia-associated thrombotic complications.

PMID- 12794147
TI  - Proteins and their derived peptides as carriers in a conjugate vaccine for
      Streptococcus pneumoniae: self-heat shock protein 60 and tetanus toxoid.
AB  - We induced T cell help for vaccination against Streptococcus pneumoniae (Pn)
      using self and foreign peptides and their source proteins conjugated to the
      capsular polysaccharide (CPS) of type 4 Pn; the carriers were self-heat shock
      protein 60 (HSP60) and tetanus toxoid (TT). We measured the production of IgG Abs
      to the CPS and the carriers, and tested resistance to challenge with highly
      lethal amounts of Pn injected i.p. (LD(50) x 10(3)-10(6)). We now report that
      vaccination protects old and young mice from bacterial challenge; however, there
      were significant differences in vaccine efficacy based on the carrier. Self-HSP60
      peptide p458m was more effective than the whole HSP60 molecule and was equally
      effective compared with TT. Both p458m and TT were more protective than the TT
      derived peptide p30 after a single vaccination. However, peptide p30 was
      effective in more MHC genotypes than was p458m. Unlike other vaccines, protection
      conferred by p458m was not related to the amount of anti-CPS Ab: mice that
      produced very little Ab were still protected from highly lethal doses of bacteria
      (LD(50) x 10(5)-10(6)). Furthermore, unlike the other carriers, there was no Ab
      response to the p458m carrier. Thus, peptides, self as well as foreign, can
      provide T cell help that differs functionally from that provided by the whole
      parent protein.

PMID- 12794148
TI  - Both lymphotoxin-alpha and TNF are crucial for control of Toxoplasma gondii in
      the central nervous system.
AB  - Immunity to Toxoplasma gondii critically depends on TNFR type I-mediated immune
      reactions, but the precise role of the individual ligands of TNFR1, TNF and
      lymphotoxin-alpha (LTalpha), is still unknown. Upon oral infection with T.
      gondii, TNF(-/-), LTalpha(-/-), and TNF/LTalpha(-/-) mice failed to control
      intracerebral T. gondii and succumbed to an acute necrotizing Toxoplasma
      encephalitis, whereas wild-type (WT) mice survived. Intracerebral inducible NO
      synthase expression and-early after infection-splenic NO levels were reduced.
      Additionally, peritoneal macrophages produced reduced levels of NO upon infection
      with T. gondii and had significantly reduced toxoplasmastatic activity in TNF(-/
      ), LTalpha(-/-), and TNF/LTalpha(-/-) mice as compared with WT animals.
      Frequencies of parasite-specific IFN-gamma-producing T cells, intracerebral and
      splenic IFN-gamma production, and T. gondii-specific IgM and IgG titers in
      LTalpha(-/-) and TNF/LTalpha(-/-) mice were reduced only early after infection.
      In contrast, intracerebral IL-10 and IL-12p40 mRNA expression and splenic IL-2,
      IL-4, and IL-12 production were identical in all genotypes. In addition, TNF(-/
      ), LTalpha(-/-), and TNF/LTalpha(-/-), but not WT, mice succumbed to infection
      with the highly attenuated ts-4 strain of T. gondii or to a subsequent challenge
      infection with virulent RH toxoplasms, although they had identical frequencies of
      IFN-gamma-producing T cells as compared with WT mice. Generation and infection of
      bone marrow reconstitution chimeras demonstrated an exclusive role of
      hematogeneously produced TNF and LTalpha for survival of toxoplasmosis. These
      findings demonstrate the crucial role of both LTalpha and TNF for control of
      intracerebral toxoplasms.

PMID- 12794149
TI  - Regulatory T cells secreting IL-10 dominate the immune response to EBV latent
      membrane protein 1.
AB  - Viruses exploit a number of strategies to evade immune recognition. In this
      study, we describe a novel mechanism by which EBV, rather than avoiding
      detection, subverts the immune response by stimulating regulatory T cells that
      secrete IL-10. Human PBMC from all EBV-seropositive, but not -seronegative,
      donors responded to both purified latent membrane protein 1 and the corresponding
      immunodominant peptides with high levels of IL-10 secretion by CD4(+) T cells.
      These IL-10 responses, characteristic of T regulatory 1 cells, inhibited T cell
      proliferation and IFN-gamma secretion induced by both mitogen and recall Ag. It
      was confirmed that the inhibition was IL-10 dependent by the use of neutralizing
      Ab. The deviation of the immune response toward suppression is likely to be
      important in maintaining latency and EBV-associated tumors.

PMID- 12794150
TI  - Variations in eosinophil chemokine responses: an investigation of CCR1 and CCR3
      function, expression in atopy, and identification of a functional CCR1 promoter.
AB  - We previously showed in a small group of donors that eosinophils from a subgroup
      of individuals responded equipotently to CC chemokine ligand (CCL)11/eotaxin and
      CCL3/macrophage-inflammatory protein-1alpha in assays of eosinophil shape change
      (CCL3/macrophage-inflammatory protein-1alpha-highly responsive (MHR) donors). In
      this study, we investigated the functional role of CCL3 in eosinophil responses
      in 73 donors. MHR donors, identified by their eosinophil shape change responses,
      represented approximately 19% of the donor pool. Eosinophils from these donors
      showed increased eosinophil CCR1 expression and also underwent CCL3-mediated
      chemotaxis and up-regulation of CD11b. All MHR donors gave a history of atopy
      associated diseases. In a further study, we prospectively recruited 110 subjects,
      subdivided into nonatopics or atopics, and investigated expression of CCR1 and
      CCR3 on eosinophils, basophils, monocytes, and neutrophils. Eosinophil CCR1
      expression was non-normally distributed in atopics, although higher CCR1
      expression levels were not predictive of a diagnosis of atopy or atopic disease.
      We identified the CCR1 promoter and investigated its function. We found a minimal
      promoter within 177 bp of the transcription start site, and an upstream enhancer
      region that facilitated expression in leukocyte cell lines. Collectively, these
      data demonstrate that MHR individuals form an important subgroup that, when
      associated with a diagnosis of allergic disease, may require tailored therapy to
      modulate eosinophil recruitment. Identification of a functional CCR1 promoter
      will facilitate the study of possible genetic determinants underlying this
      potentially important clinical phenotype.

PMID- 12794151
TI  - Regulation of chemokine mRNA stability by lipopolysaccharide and IL-10.
AB  - IL-10 has been reported to inhibit the expression of LPS-induced proinflammatory
      cytokines and chemokines by altering the rate of specific mRNA decay although the
      molecular target(s) for its action remain unknown. In the present study, using
      primary peritoneal exudate macrophages and a cell culture model in which a
      tetracycline-responsive promoter controls transcription of CXC ligand 1 (KC)
      mRNA, we demonstrate that LPS promotes a time-dependent increase in KC mRNA
      stability. Although IL-10 had no direct effect on mRNA decay, this treatment
      antagonized the stabilizing action of LPS. The mechanisms involved were further
      explored using a cell-free mRNA degradation system. A 5'-capped, polyadenylated
      in vitro transcript derived from the 3'-untranslated region of KC mRNA exhibited
      time-dependent decay in the presence of protein extracts prepared from untreated
      RAW264.7 macrophages. Extracts prepared from LPS-treated RAW264.7 cells had
      reduced decay activity and this change was antagonized if the cells were
      costimulated with IL-10. A substrate in which the AU-rich element motifs were
      mutated exhibited minimal decay that did not vary using extracts prepared from
      cells treated with LPS or LPS and IL-10. A nonadenylated RNA substrate was also
      degraded and that activity was diminished by LPS. In concert, these findings
      demonstrate that KC mRNA stability is regulated by LPS-induced alterations in
      activities that govern both deadenylation and degradation of the mRNA body. The
      effects of IL-10 on KC mRNA stability reflect antagonism of the response to LPS.

PMID- 12794152
TI  - Fas (CD95) induces proinflammatory cytokine responses by human monocytes and
      monocyte-derived macrophages.
AB  - Fas (CD95, APO-1) is regarded as the prototypical cell death receptor of the TNFR
      superfamily. Fas-induced apoptosis is generally considered to be a
      noninflammatory process, contributing to the silent resolution of immune and
      inflammatory responses. However, accumulating evidence indicates that Fas may
      also induce cellular activation signals. We hypothesized that Fas could activate
      proinflammatory cytokine responses by normal human monocytes and macrophages.
      Monocytes were isolated by negative immunoselection from the PBMC fraction of
      venous blood from healthy volunteers, and monocyte-derived macrophages were
      cultivated in vitro. Both monocytes and monocyte-derived macrophages released TNF
      alpha and IL-8 following Fas ligation, and conditioned medium from Fas-activated
      monocytes and macrophages induced the directed migration of neutrophils in a
      chemotaxis assay. Fas-induced monocyte cytokine responses were associated with
      monocyte apoptosis, nuclear translocation of NF-kappaB, and cytokine gene
      expression and were blocked by caspase inhibition but not by inhibition of IL
      1beta signaling. In contrast, Fas-induced macrophage cytokine responses occurred
      in the absence of apoptosis and were caspase independent, indicating maturation
      dependent differences in the Fas signaling pathways that lead to proinflammatory
      cytokine induction. Rather than contributing to the resolution of inflammation,
      Fas ligation on circulating monocytes and tissue macrophages may induce
      proinflammatory cytokine responses that can initiate acute inflammatory responses
      and tissue injury.

PMID- 12794153
TI  - Induction of macrophage nitric oxide production by Gram-negative flagellin
      involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4
      complexes.
AB  - The induction of cytokine synthesis by flagellin is mediated by a Toll-like
      receptor 5 (TLR5) signaling pathway. Although flagellin activation of the IL-1R
      associated kinase and induction of TNF-alpha synthesis are dependent on TLR5 and
      not TLR4, we have found that flagellin stimulates NO in macrophages via a pathway
      that requires TLR5 and TLR4. Flagellin induced NO synthesis in HeNC2 cells, a
      murine macrophage cell line that expresses wild-type TLR4, but not in TLR4-mutant
      or -deficient GG2EE and 10ScNCr/23 cells. Flagellin stimulated an increase in
      inducible NO synthase (iNOS) mRNA and activation of the iNOS promoter. TLR5 forms
      heteromeric complexes with TLR4 as well as homomeric complexes. IFN-gamma
      permitted GG2EE and 10ScNCr/23 cells to produce NO in response to flagellin.
      Flagellin stimulated IFN-beta synthesis and Stat1 activation. The effect of
      flagellin on iNOS gene expression was inhibited by a Stat1 mutant protein. Taken
      together, these results support the conclusions that flagellin induces distinct
      patterns of inflammatory mediators depending on the nature of the TLR5 signaling
      complex and that the induction of NO by flagellin involves signaling via
      TLR5/TLR4 complexes.

PMID- 12794154
TI  - Activation of NF-kappa B in virus-infected macrophages is dependent on
      mitochondrial oxidative stress and intracellular calcium: downstream involvement
      of the kinases TGF-beta-activated kinase 1, mitogen-activated
      kinase/extracellular signal-regulated kinase kinase 1, and I kappa B kinase.
AB  - Efficient clearance of virus infections depends on the nature of the host
      response raised by the infected organism. A proinflammatory cell-mediated immune
      response is important for elimination of many viruses, including herpesviruses.
      Macrophages are intimately involved in generation of a proinflammatory response,
      the initiation of which involves activation of the transcription factor NF
      kappaB. However, the mechanisms of HSV-induced NF-kappaB activation are poorly
      understood. In this study we demonstrate that activation of NF-kappaB by HSV in
      macrophages is dependent on a functional viral genome and proceeds through a
      mechanism involving the cellular IkappaB kinase, as well as the upstream kinases
      TGF-beta-activated kinase 1, mitogen-activated kinase/extracellular signal
      regulated kinase kinase 1, and possibly NF-kappaB-inducing kinase. Furthermore,
      we show that HSV triggers NF-kappaB activation by a signaling pathway involving
      oxidative stress in mitochondria and intracellular calcium, because specific
      inhibition of mitochondria-derived reactive oxygen intermediates, as well as
      mitochondrial calcium channels, prevented NF-kappaB activation. Together, these
      results point to mitochondria as cellular checkpoints able to initiate NF-kappaB
      activation after virus infection and also show that the cellular NF-kappaB
      regulating kinases IkappaB kinase, TGF-beta-activated kinase 1, mitogen-activated
      kinase/extracellular signal-regulated kinase kinase 1, and possibly NF-kappaB
      inducing kinase, are essential components in the HSV-induced signaling pathway.

PMID- 12794155
TI  - Corneal IL-8 expression following adenovirus infection is mediated by c-Src
      activation in human corneal fibroblasts.
AB  - Emerging evidence indicates that intracellular signaling cascades mediate entry
      of pathogenic adenoviruses into target host cells as well as some of the
      undesirable inflammatory responses to adenoviral gene vectors. We found that Ad19
      infection of cultured human corneal fibroblasts induced IL-8 gene transcription
      independently of IL-1beta, TNF-alpha, and viral gene expression, suggesting that
      intracellular signaling events might mediate early inflammatory events in
      adenovirus keratitis. Heat but not UV light inactivation of the virus abrogated
      the effect of infection on IL-8 mRNA and protein levels, consistent with a viral
      binding-mediated mechanism. The tyrosine kinase inhibitor herbimycin blocked Ad19
      induced IL-8 expression. Western blot analysis revealed tyrosine phosphorylation
      of the functionally related kinases c-Src and extracellular signal-regulated
      kinase (ERK) 1/2 in corneal fibroblasts within 15 min after infection. Respective
      inhibitors of these kinases, PP2 and PD98059, also blocked Ad19-induced IL-8 mRNA
      and protein expression. Application of inhibitors to Src and ERK kinase assays
      suggested an upstream relationship of c-Src to ERK. Finally, DNA microarray
      studies performed 1 h after Ad19 or mock infection of corneal fibroblasts in the
      presence or absence of the Src-specific inhibitor PP2 confirmed a relationship
      between c-Src and IL-8 expression in Ad19-infected corneal cells. c-Src may act
      as a global regulator of early proinflammatory host responses to Ad19 infection
      of the human cornea.

PMID- 12794156
TI  - Differential regulation of lipopolysaccharide-induced monocyte matrix
      metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated
      kinase 1/2 mitogen-activated protein kinases.
AB  - Signal transduction events in monocyte matrix metalloproteinase (MMP) production
      have been shown to include a PGE(2)-cAMP-dependent step. To determine earlier
      pathway components, we examined the role of mitogen-activated protein kinases
      (MAPKs) in the regulation of monocyte MMP-1 and MMP-9, two major MMPs induced by
      LPS. Stimulation with LPS resulted in the activation of the extracellular signal
      regulated kinase 1 and 2 (ERK1/2) and mitogen-activated kinase p38. The p38
      specific inhibitor SB203580 suppressed p38 activity and MMP-1 mRNA and protein,
      but increased ERK activity and MMP-9 mRNA and protein. In contrast, the MAPK
      kinase 1/2-specific inhibitor PD98059 inhibited MMP-1 and MMP-9. However, both
      MAPK inhibitors decreased the production of cyclooxygenase-2 and PGE(2), but only
      the inhibition of MMP-1 by SB203580 was reversed by PGE(2) or dibutyryl cAMP.
      Examination of the effect of these MAPK inhibitors on the promoters of MMP-1 and
      MMP-9 revealed that PD98059 inhibited the binding of transcription factors to all
      of the MMP promoter-specific complementary oligonucleotides tested. However,
      SB203580 only inhibited the binding of MMP-1-specific CREB and SP 1
      oligonucleotides, which was reversed by PGE(2). Additionally, SB203580 enhanced
      transcription factor binding to the oligonucleotides complementary to a NF-kappaB
      site in the promoter of MMP-9. Thus, LPS induction of MMP-1 production by
      monocytes is regulated by both ERK1/2 and p38, whereas MMP-9 stimulation occurred
      mainly through the ERK1/2 pathway. Moreover, p38 regulates MMP-1 mainly through a
      PGE(2)-dependent pathway, whereas ERK1/2-mediated MMP-1 and MMP-9 production
      involves the activation of additional MMP promoter sites through a PGE(2)
      independent mechanism.

PMID- 12794157
TI  - Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass
      and function.
AB  - Transplantation of an excessive number of islets of Langerhans (two to four
      pancreata per recipient) into patients with type I diabetes is required to
      restore euglycemia. Hypoxia, nutrient deprivation, local inflammation, and the
      beta cell inflammatory response (up-regulation of NF-kappaB-dependent genes such
      as inos) result in beta cell destruction in the early post-transplantation
      period. Genetic engineering of islets with anti-inflammatory and antiapoptotic
      genes may prevent beta cell loss and primary nonfunction. We have shown in vitro
      that A20 inhibits NF-kappaB activation in islets and protects from cytokine- and
      death receptor-mediated apoptosis. In vivo, protection of newly transplanted
      islets would reduce the number of islets required for successful transplantation.
      Transplantation of 500 B6/AF(1) mouse islets into syngeneic, diabetic recipients
      resulted in a cure rate of 100% within 5 days. Transplantation of 250 islets
      resulted in a cure rate of only 20%. Transplantation of 250 islets overexpressing
      A20 resulted in a cure rate of 75% with a mean time to cure of 5.2 days,
      comparable to that achieved with 500 islets. A20-expressing islets preserve
      functional beta cell mass and are protected from cell death. These data
      demonstrate that A20 is an ideal cytoprotective gene therapy candidate for islet
      transplantation.

PMID- 12794158
TI  - A prominent role for airway epithelial NF-kappa B activation in
      lipopolysaccharide-induced airway inflammation.
AB  - To reveal the causal role of airway epithelial NF-kappaB activation in evoking
      airway inflammation, a transgenic mouse was created expressing a mutant version
      of the inhibitory protein I-kappaBalpha. This I-kappaBalpha superrepressor (I
      kappaBalpha(SR)) acts to repress NF-kappaB activation exclusively in airway
      epithelial cells, under the transcriptional control of the rat CC10 promoter
      (CC10-I-kappaBalpha(SR)). Compared with transgene-negative littermates,
      intranasal instillation of LPS did not induce nuclear translocation of NF-kappaB
      in airway epithelium of CC10-I-kappaBalpha(SR) transgenic mice. Consequently, the
      influx of neutrophils into the airways and secretion of the NF-kappaB-regulated
      neutrophilic chemokine, macrophage-inflammatory protein-2, and the inflammatory
      cytokine, TNF-alpha, were markedly reduced in CC10-I-kappaBalpha(SR) mice
      relative to the transgene-negative mice exposed to LPS. Despite an inability to
      activate NF-kappaB in airway epithelium, resident alveolar macrophages from
      transgene-positive mice were capable of activating NF-kappaB in a manner
      indistinguishable from transgene-negative mice. These findings demonstrate that
      airway epithelial cells play a prominent role in orchestrating the airway
      inflammatory response to LPS and suggest that NF-kappaB signaling in these cells
      is important for modulating innate immune responses to microbial products.

PMID- 12794160
TI  - Transepithelial migration of neutrophils in response to leukotriene B4 is
      mediated by a reactive oxygen species-extracellular signal-regulated kinase
      linked cascade.
AB  - The epithelial cells that form a barrier lining the lung airway are key
      regulators of neutrophil trafficking into the airway lumen in a variety of lung
      inflammatory diseases. Although the lipid mediator leukotriene B(4) (LTB(4)) is
      known to be a principal chemoattractant for recruiting neutrophils to inflamed
      sites across the airway epithelium, the precise signaling mechanism involved
      remains largely unknown. In the present study, therefore, we investigated the
      signaling pathway through which LTB(4) induces transepithelial migration of
      neutrophils. We found that LTB(4) induces concentration-dependent transmigration
      of DMSO-differentiated HL-60 neutrophils and human polymorphonuclear neutrophils
      across A549 human lung epithelium. This effect was mediated via specific LTB(4)
      receptors and was inhibited by pretreating the cells with N-acetylcysteine (NAC),
      an oxygen free radical scavenger, with diphenylene iodonium (DPI), an inhibitor
      of NADPH oxidase-like flavoproteins, or with PD98059, an extracellular signal
      regulated kinase (ERK) inhibitor. Consistent with those findings, LTB(4)-induced
      ERK phosphorylation was completely blocked by pretreating cells with NAC or DPI.
      Taken together, our observations suggest LTB(4) signaling to transepithelial
      migration is mediated via generation of reactive oxygen species, which leads to
      downstream activation of ERK. The physiological relevance of this signaling
      pathway was demonstrated in BALB/c mice, in which intratracheal instillation of
      LTB(4) led to acute recruitment of neutrophils into the airway across the lung
      epithelium. Notably, the response to LTB(4) was blocked by NAC, DPI, PD98059, or
      CP105696, a specific LTB(4) receptor antagonist.

PMID- 12794159
TI  - Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated
      kinase-dependent TNF-alpha secretion from human T cells.
AB  - Lipoxins (LX) and their aspirin-triggered 15-epimer endogenous isoforms are
      endogenous anti-inflammatory and pro-resolution eicosanoids. In this study, we
      examined the impact of LX and aspirin-triggered LXA(4)-stable analogs (ATLa) on
      human T cell functions. 15-epi-16-(p-fluoro)phenoxy-LXA(4) (ATLa(1)) blocked the
      secretion of TNF-alpha from human PBMC after stimulation by anti-CD3 Abs, with
      the IC(50) value of approximately 0.05 nM. A similar action was also exerted by
      the native aspirin-triggered 15-epi-LXA(4), a new 15-epi-16-(p-trifluoro)phenoxy
      LXA(4) analog (ATLa(2)), as well as LXB(4), and its analog 5-(R/S)-methyl-LXB(4).
      The LXA(4) receptor (ALX) is expressed in peripheral blood T cells and mediates
      the inhibition of TNF-alpha secretion from activated T cells by ATLa(1). This
      action was accomplished by inhibition of the anti-CD3-induced activation of
      extracellular signal-regulated kinase, which is essential for TNF-alpha secretion
      from anti-CD3-activated T cells. These results demonstrate novel roles for LX and
      aspirin-triggered LX in the regulation of T cell-mediated responses relevant in
      inflammation and its resolution. Moreover, they provide potential
      counterregulatory signals in communication(s) between the innate and acquired
      immune systems.

PMID- 12794161
TI  - Differential activation of NF-kappa B, AP-1, and C/EBP in endotoxin-tolerant
      rats: mechanisms for in vivo regulation of glomerular RANTES/CCL5 expression.
AB  - Chemokines play a pivotal role in the regulation of inflammatory cell
      infiltration in glomerular immune injury. To characterize mechanisms relevant for
      the regulation of chemokine expression in vivo, the LPS-mediated model of renal
      inflammation in rats was used in which we have previously demonstrated that the
      chemokine RANTES/CCL5 is expressed and secreted in glomeruli. Glomerular
      RANTES/CCL5 expression in this model correlated with an increased glomerular
      binding activity of the transcription factors AP-1, C/EBP, and NF-kappaB. To gain
      further insight into the functional roles of these transcription factors in the
      regulation of glomerular RANTES/CCL5 expression, we cloned the rat RANTES/CCL5
      promoter and established the model of in vivo LPS tolerance. In tolerant rats,
      LPS-induced glomerular RANTES/CCL5 expression and activation of the transcription
      factors AP-1 and C/EBP were significantly reduced using both consensus and rat
      RANTES/CCL5-specific oligonucleotides. Reduced glomerular NF-kappaB binding
      activity after LPS injection could be demonstrated in tolerant rats only when
      using rat RANTES/CCL5-specific oligonucleotides. Reduced binding activity to this
      RANTES/CCL5-specific NF-kappaB binding site in the context of broad NF-kappaB
      activation might be due to changes in transcription factor interactions or
      chromatin remodeling processes.

PMID- 12794162
TI  - Fas is detectable on beta cells in accelerated, but not spontaneous, diabetes in
      nonobese diabetic mice.
AB  - Fas (CD95) is a potential mechanism of pancreatic beta cell death in type 1
      diabetes. beta cells do not constitutively express Fas but it is induced by
      cytokines. The hypothesis of this study is that Fas expression should be
      measurable on beta cells for them to be killed by this mechanism. We have
      previously reported that up to 5% of beta cells isolated from nonobese diabetic
      (NOD) mice are positive for Fas expression by flow cytometry using
      autofluorescence to identify beta cells. We have now found that these are not
      beta cells but contaminating dendritic cells, macrophages, and B lymphocytes. In
      contrast beta cells isolated from NODscid mice that are recipients of T
      lymphocytes from diabetic NOD mice express Fas 18-25 days after adoptive transfer
      but before development of diabetes. Fas expression on beta cells was also
      observed in BDC2.5, 8.3, and 4.1 TCR-transgenic models of diabetes in which
      diabetes occurs more rapidly than in unmodified NOD mice. In conclusion, Fas is
      observed on beta cells in models of diabetes in which rapid beta cell destruction
      occurs. Its expression is likely to reflect differences in the intraislet
      cytokine environment compared with the spontaneous model and may indicate a role
      for this pathway in beta cell destruction in rapidly progressive models.

PMID- 12794163
TI  - A role for macrophage inflammatory protein-3 alpha/CC chemokine ligand 20 in
      immune priming during T cell-mediated inflammation of the central nervous system.
AB  - Chemokines are a family of cytokines that exhibit selective chemoattractant
      properties for target leukocytes and play a significant role in leukocyte
      migration. In this study, we have investigated the role of the C-C chemokine,
      macrophage inflammatory protein (MIP)-3alpha/CC chemokine ligand 20, in the
      pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of T
      cell-dependent inflammation. Expression in the CNS of MIP-3alpha, as determined
      by RT-PCR, increased in a time-dependent manner such that peak expression
      correlated with peak clinical disease. Similarly, levels of immunoreactive MIP
      3alpha in the draining lymph nodes increased up to 10-fold 9 days
      postimmunization and remained elevated for up to 21 days postimmunization. The
      increased production of MIP-3alpha coincided with onset of clinical disease.
      Treatment of mice with specific neutralizing anti-MIP-3alpha Abs significantly
      reduced the severity of both clinical EAE and neuroinflammation by inhibiting the
      sensitization of lymphocytes to the specific Ag and release of lymphocytes from
      the draining lymph nodes. In contrast, adoptive transfer experiments indicated
      that MIP-3alpha was not essential for the effector phase of EAE. Together, these
      data demonstrate that MIP-3alpha plays a critical role in the sensitization phase
      of EAE.

PMID- 12794164
TI  - An inducible nitric oxide synthase-luciferase reporter system for in vivo testing
      of anti-inflammatory compounds in transgenic mice.
AB  - The inducible NO synthase gene (iNOS) plays a role in a number of chronic and
      acute conditions, including septic shock and contact hypersensitivity autoimmune
      diseases, such as rheumatoid arthritis, gastrointestinal disorders, and
      myocardial ischemia. The iNOS gene is primarily under transcriptional control and
      is induced in a variety of conditions. The ability to monitor and quantify iNOS
      expression in vivo may facilitate a better understanding of the role of iNOS in
      different diseases. In this study, we describe a transgenic mouse (iNos-luc) in
      which the luciferase reporter is under control of the murine iNOS promoter. In an
      acute sepsis model produced by injection of IFN-gamma and LPS, we observed an
      induction of iNOS-driven luciferase activity in the mouse liver. This transgene
      induction is dose and time dependent and correlated with an increase of liver
      iNOS protein and iNOS mRNA levels. With this model, we tested 11 compounds
      previously shown to inhibit iNOS induction in vitro or in vivo. Administration of
      dexamethasone, epigallocatechin gallate, alpha-phenyl-N-tert-butyl nitrone, and
      ebselen significantly suppressed iNOS transgene induction by IFN-gamma and LPS.
      We further evaluated the use of the iNos-luc transgenic mice in a zymosan-induced
      arthritis model. Intra-articular injection of zymosan induced iNos-luc expression
      in the knee joint. The establishment of the iNos-luc transgenic model provides a
      valuable tool for studying processes in which the iNOS gene is induced and for
      screening anti-inflammatory compounds in vivo.

PMID- 12794165
TI  - Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+
      T and CCR7 B and T lymphocytes in thyroid autoimmune diseases.
AB  - Chemokines and their corresponding receptors are crucial for the recruitment of
      lymphocytes into the lymphoid organs and for its organization acting in a
      multistep process. Tissues affected by autoimmune disease often contain ectopic
      lymphoid follicles which, in the case of autoimmune thyroid disorders, are highly
      active and specific for thyroid Ags although its pathogenic role remains unclear.
      To understand the genesis of these lymphoid follicles, the expression of relevant
      cytokines and chemokines was assessed by real time PCR, immunohistochemistry and
      by in vitro assays in autoimmune and nonautoimmune thyroid glands. Lymphotoxin
      alpha, lymphotoxin beta, C-C chemokine ligand (CCL) 21, CXC chemokine ligand
      (CXCL) 12, CXCL13, and CCL22 were increased in thyroids from autoimmune patients,
      whereas CXCL12, CXCL13, and CCL22 levels were significantly higher in autoimmune
      glands with ectopic secondary lymphoid follicles than in those without follicles.
      Interestingly, thyroid epithelium produced CXCL12 in response to proinflammatory
      cytokines providing a possible clue for the understanding of how tissue stress
      may lead to ectopic follicle formation. The finding of a correlation between
      chemokines and thyroid autoantibodies further suggests that intrathyroidal
      germinal centers play a significant role in the autoimmune response.
      Unexpectedly, the percentage of circulating CXCR4(+) T cells and CCR7(+) B and T
      cells (but not of CXCR5) was significantly reduced in PBMCs of patients with
      autoimmune thyroid disease when they were compared with their intrathyroidal
      lymphocytes. This systemic effect of active intrathyroidal lymphoid tissue
      emerges as a possible new marker of thyroid autoimmune disease activity.

PMID- 12794166
TI  - Coordinate regulation of IFN consensus sequence-binding protein and caspase-1 in
      the sensitization of human colon carcinoma cells to Fas-mediated apoptosis by IFN
      gamma.
AB  - Interferon-gamma is thought to be essential for the regulation of antitumor
      reactions. However, the degree of responsiveness of malignant cells to IFN-gamma
      may have a profound influence on the overall efficacy of an antitumor response.
      In this study, we examined the molecular basis by which IFN-gamma differentially
      sensitized human primary and metastatic colon carcinoma cells to Fas-mediated
      apoptosis. To that end, we analyzed IFN-gamma-induced gene expression at the
      genome scale, followed by an analysis of the expression and function of specific
      genes associated with IFN-gamma- and Fas-mediated signaling. We found that
      although both cell populations exhibited a similar gene expression profile at the
      genome scale in response to IFN-gamma, the expression intensities of the IFN
      gamma-regulated genes were much greater in the primary tumor. Noteworthily, two
      genes, one involved in IFN-gamma-mediated signaling, IFN consensus sequence
      binding protein (ICSBP), and one involved in Fas-mediated signaling, caspase-1,
      were clearly shown to be differentially induced between the two cell lines. In
      the primary tumor cells, the expression of ICSBP and caspase-1 was strongly
      induced in response to IFN-gamma, whereas they were weakly to nondetectable in
      the metastatic tumor cells. Functional studies demonstrated that both caspase-1
      and ICSBP were involved in Fas-mediated apoptosis following IFN-gamma
      sensitization, but proceeded via two distinct pathways. This study also reports
      for the first time the expression of ICSBP in a nonhemopoietic tumor exhibiting
      proapoptotic properties. Overall, in a human colon carcinoma cell model, we
      identified important functional contributions of two IFN-gamma-regulated genes,
      ICSBP and caspase-1, in the mechanism of Fas-mediated death.

PMID- 12794167
TI  - Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and
      CTL adoptive immunotherapy.
AB  - CD8(+) CTL play important roles against malignancy in both active and passive
      immunotherapy. Nonetheless, the success of antitumor CTL responses may be
      improved by additional therapeutic modalities. Radiotherapy, which has a long
      standing use in treating neoplastic disease, has been found to induce unique
      biologic alterations in cancer cells affecting Fas gene expression, which,
      consequently, may influence the overall lytic efficiency of CTL. Here, in a mouse
      adenocarcinoma cell model, we examined whether exposure of these tumor cells to
      sublethal doses of irradiation 1) enhances Fas expression, leading to more
      efficient CTL killing via Fas-dependent mechanisms in vitro; and 2) improves
      antitumor activity in vivo by adoptive transfer of these Ag-specific CTL.
      Treatment of carcinoembryonic Ag-expressing MC38 adenocarcinoma cells with
      irradiation (20 Gy) in vitro enhanced Fas expression at molecular, phenotypic,
      and functional levels. Furthermore, irradiation sensitized these targets to Ag
      specific CTL killing via the Fas/Fas ligand pathway. We examined the effect of
      localized irradiation of s.c. growing tumors on the efficiency of CTL adoptive
      immunotherapy. Irradiation caused up-regulation of Fas by these tumor cells in
      situ, based on immunohistochemistry. Moreover, localized irradiation of the tumor
      significantly potentiated tumor rejection by these carcinoembryonic Ag-specific
      CTL. Overall, these results showed for the first time that 1) regulation of the
      Fas pathway in tumor cells by irradiation plays an important role in their
      sensitization to Ag-specific CTL; and 2) a combination regimen of tumor-targeted
      irradiation and CTL promotes more effective antitumor responses in vivo, which
      may have implications for the combination of immunotherapy and radiation therapy.

PMID- 12794168
TI  - Immunoglobulin activation of T cell chemoattractant expression in fibroblasts
      from patients with Graves' disease is mediated through the insulin-like growth
      factor I receptor pathway.
AB  - Graves' disease (GD) is associated with T cell infiltration, but the mechanism
      for lymphocyte trafficking has remained uncertain. We reported previously that
      fibroblasts from patients with GD express IL-16, a CD4-specific chemoattractant,
      and RANTES, a C-C chemokine, in response to GD-specific IgG (GD-IgG). We
      unexpectedly found that these responses result from a functional interaction
      between GD-IgG and the insulin-like growth factor (IGF)-I receptor (IGF-IR). IGF
      I and the IGF-IR-specific IGF-I analog, des(1-3), mimic the effects of GD-IgG.
      Neither GD-IgG nor IGF-I activates chemoattractant expression in control
      fibroblasts from donors without GD. Interrupting IGF-IR function with specific
      receptor-blocking Abs or by transiently transfecting fibroblasts with a dominant
      negative mutant IGF-IR completely attenuates signaling provoked by GD-IgG.
      Moreover, GD-IgG displaces specific (125)I-labeled IGF-I binding to fibroblasts
      and attenuates IGF-IR detection by flow cytometry. These findings identify a
      novel disease mechanism involving a functional GD-IgG/IGF-IR bridge, which
      potentially explains T cell infiltration in GD. Interrupting this pathway may
      constitute a specific therapeutic strategy.

PMID- 12794169
TI  - Failure of monocytes of trauma patients to convert to immature dendritic cells is
      related to preferential macrophage-colony-stimulating factor-driven macrophage
      differentiation.
AB  - Following trauma, increased inflammatory monokine activation and depressed APC
      function can occur simultaneously. These contradictory monocyte (Mphi)
      dysfunctions could result if postinjury Mphi differentiation preferentially
      favored inflammatory macrophage (Mac) differentiation over development into the
      most potent APC, dendritic cells (DC). In this report, Mphi of trauma patients
      with a depressed MLR induction capacity are, for the first time, shown to be
      unable to differentiate in vitro to immature CD1a(+) DC under the influence of GM
      CSF and IL-4. Trauma patient Mphi that retained MLR-inducing capacity had a
      nonsignificant reduction in DC differentiation capacity. Only patient Mphi
      populations with depressed differentiation to immature DC (iDC) demonstrated
      depressed IL-12 and IL-15 production and a continued reduced MLR induction
      capacity. Neither increased IL-10 production nor decreased CD11c(+) DC precursor
      numbers correlated with depressed Mphi-to-DC differentiation. Instead, these
      patients' APC-dysfunctional Mphi populations had increased expression of
      inflammatory Mac phenotypes (CD64(+), CD86(low), HLA-DR(low)) and up-regulated
      secretion of M-CSF. M-CSF combined with IL-6 inhibits Mphi-to-iDC differentiation
      and promotes Mphi-to-Mac differentiation by down-regulating GM-CSFR expression
      and increasing DC apoptosis. Both depressed GM-CSFR expression and increased Mphi
      iDC apoptosis, as well as increased expression of CD126 (IL-6R) and CD115 (M
      CSFR), were detected in APC-defective patient Mphi. In vitro addition of anti-M
      CSF enhanced the IL-4 plus GM-CSF-induced Mphi-to-DC differentiation of these
      patients. This suggests that, in trauma patients, enhanced Mphi-to-Mac
      differentiation with concomitant inhibited iDC development is partially due to
      increased circulating Mphi sensitivity to and production of M-CSF and contributes
      to postinjury immunoaberrations.

PMID- 12794170
TI  - Identification of a mutated receptor-like protein tyrosine phosphatase kappa as a
      novel, class II HLA-restricted melanoma antigen.
AB  - Recent studies increasingly point to a pivotal role of CD4(+) T cells in human
      anti-tumor immune response. Here we show that lymphocytes purified from a tumor
      infiltrated lymph node of a melanoma patient that had remained disease free for
      10 years after surgical resection of a lymph node metastasis comprised
      oligoclonal class II HLA-restricted CD4(+) T cells recognizing the autologous
      tumor cells in vitro. In fact, the CD4(+) T cell clones isolated from these
      lymphocytes displayed a tumor-specific, cytotoxic activity in addition to a Th1
      like cytokine profile. By a genetic approach, a peptide derived from a mutated
      receptor-like protein tyrosine phosphatase kappa was identified as a novel HLA
      DR10-restricted epitope for all the melanoma-specific CD4(+) T cell clones. The
      immunogenic peptide was shown to contain the mutated residue that was crucial for
      T cell recognition and activation. Moreover, a systemic immunity against the
      mutated peptide was detectable in the patient's peripheral blood T lymphocytes
      obtained during the disease-free period of follow-up. These findings further
      support the relevance of CD4(+) T cells directed against mutated epitopes in
      tumor immunity and provide the rationale for a possible usage of mutated, tumor
      specific Ags for immunotherapy of human cancer.

PMID- 12794171
TI  - Characterization of the antigen specificity and TCR repertoire, and TCR-based DNA
      vaccine therapy in myelin basic protein-induced autoimmune encephalomyelitis in
      DA rats.
AB  - Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)
      susceptible strain and develop severe EAE upon immunization with myelin basic
      protein (MBP). However, there are several differences between the two strains. In
      the present study we induced acute EAE in DA rats by immunization with MBP and
      MBP peptides and examined the Ag specificity and TCR repertoire of
      encephalitogenic T cells. It was found that although immunization with MBP and a
      peptide corresponding to its 62-75 sequence (MBP(62-75)) induced clinical EAE,
      the responses of lymph node T cells isolated from MBP-immunized rats to MBP(62
      75) was marginal, indicating that this peptide contains major encephalitogenic,
      but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of
      spinal cord T cells revealed that Vbeta10 and Vbeta15 spectratype expansion was
      always found in MBP(62-75)-immunized symptomatic rats. On the basis of these
      findings, we examined the encephalitogenicity of Vbeta10- and Vbeta15-positive T
      cells. First, the adoptive transfer experiments revealed that Vbeta10-positive T
      line cells derived from MBP(62-75)-immunized rats induced clinical EAE in
      recipients. Second, administration of DNA vaccines encoding Vbeta10 and Vbeta15,
      alone or in combination, ameliorated MBP(62-75)-induced EAE. Collectively, it was
      strongly suggested that Vbeta10- and Vbeta15-positive T cells are
      encephalitogenic. Analyses of the Ag specificity and T cell repertoire of
      pathogenic T cells performed in this study provide useful information for
      designing specific immunotherapies against autoimmune diseases.

PMID- 12794172
TI  - The distinct roles of the N-terminal copper-binding sites in regulation of
      catalytic activity of the Wilson's disease protein.
AB  - Wilson's disease protein (WNDP) is a copper-transporting ATPase essential for
      normal distribution of copper in human cells. Recent studies demonstrate that
      copper regulates WNDP through several mechanisms. Six metal-binding sites (MBS)
      at the N terminus of WNDP are predicted to be involved in copper-dependent
      regulation of WNDP; however, specific roles of MBS remain poorly understood. To
      address this issue, we generated WNDP variants with mutations or truncation in
      the N-terminal region and characterized their functional properties. We show that
      copper cooperatively stimulates catalytic activity of WNDP and that this effect
      requires the presence of both MBS5 and MBS6. Mutations of MBS6 or MBS1-5 result
      in non-cooperative activation of the enzyme by copper, whereas the deletion of
      MBS1-4 does not abolish cooperativity. Our data further suggest that MBS5 and
      MBS6 together regulate the affinity of the intramembrane-binding site(s) for
      copper. Analysis of the copper-dependent stimulation of catalytic phosphorylation
      demonstrate that the MBS6 and MBS1-5 mutants have a 7-8-fold lower EC50 for
      copper activation, suggesting that their affinity for copper is increased. This
      conclusion is confirmed by a markedly decreased inhibition of these mutants by a
      copper chelator bathocuproine disulphonate. In contrast, deletion of MBS1-4 does
      not affect the affinity of sites important for catalytic phosphorylation. Rather,
      the MBS1-4 region appears to control access of copper to the functionally
      important metal-binding sites. The implications of these findings for
      intracellular regulation of WNDP are discussed.

PMID- 12794173
TI  - Molecular dissection of the inward rectifier potassium current (IK1) in rabbit
      cardiomyocytes: evidence for heteromeric co-assembly of Kir2.1 and Kir2.2.
AB  - Cardiac inward rectifier K+ currents (IK1) play an important role in maintaining
      resting membrane potential and contribute to late phase repolarization. Members
      of the Kir2.x channel family appear to encode for IK1. The purpose of this study
      was to determine the molecular composition of cardiac IK1 in rabbit ventricle.
      Western blots revealed that Kir2.1 and Kir2.2, but not Kir2.3, are expressed in
      rabbit ventricle. Culturing rabbit myocytes resulted in an approximately 50%
      reduction of IK1 density after 48 or 72 h in culture which was associated with an
      80% reduction in Kir2.1, but no change in Kir2.2, protein expression. Dominant
      negative (DN) constructs of Kir2.1, Kir2.2 and Kir2.3 were generated and tested
      in tsA201 cells. Adenovirus-mediated over-expression of Kir2.1dn, Kir2.2dn or
      Kir2.1dn plus Kir2.2dn in cultured rabbit ventricular myocytes reduced IK1
      density equally by 70% 72 h post-infection, while AdKir2.3dn had no effect,
      compared to green fluorescent protein (GFP)-infected myocytes. Previous studies
      indicate that the [Ba2+] required for half-maximum block (IC50) differs
      significantly between Kir2.1, Kir2.2 and Kir2.3 channels. The dependence of IK1
      on [Ba2+] revealed a single binding isotherm which did not change with time in
      culture. The IC50 for block of IK1 was also unaffected by expression of the
      different DN genes after 72 h in culture. Taken together, these results
      demonstrate functional expression of Kir2.1 and Kir2.2 in rabbit ventricular
      myocytes and suggest that macroscopic IK1 is predominantly composed of Kir2.1 and
      Kir2.2 heterotetramers.

PMID- 12794174
TI  - UCP3 protein regulation in human skeletal muscle fibre types I, IIa and IIx is
      dependent on exercise intensity.
AB  - It has been proposed that mitochondrial uncoupling protein 3 (UCP3) behaves as an
      uncoupler of oxidative phosphorylation. In a cross-sectional study, UCP3 protein
      levels were found to be lower in all fibre types of endurance-trained cyclists as
      compared to healthy controls. This decrease was greatest in the type I oxidative
      fibres, and it was hypothesised that this may be due to the preferential
      recruitment of these fibres during endurance training. To test this hypothesis,
      we compared the effects of 6 weeks of endurance (ETr) and sprint (STr) running
      training on UCP3 mRNA expression and fibre-type protein content using real-time
      PCR and immunofluorescence techniques, respectively. UCP3 mRNA and protein levels
      were downregulated similarly in ETr and STr (UCP3 mRNA: by 65 and 50%,
      respectively; protein: by 30 and 27%, respectively). ETr significantly reduced
      UCP3 protein content in type I, IIa and IIx muscle fibres by 54, 29 and 16%,
      respectively. STr significantly reduced UCP3 protein content in type I, IIa and
      IIx muscle fibres by 24, 31 and 26%, respectively. The fibre-type reductions in
      UCP3 due to ETr, but not STr, were significantly different from each other, with
      the effect being greater in type I than in type IIa, and in type IIa than in type
      IIx fibres. As a result, compared to STr, ETr reduced UCP3 expression
      significantly more in fibre type I and significantly less in fibre types IIx.
      This suggests that the more a fibre is recruited, the more it adapts to training
      by a decrease in its UCP3 expression. In addition, the more a fibre type depends
      on fatty acid beta oxidation and oxidative phosphorylation, the more it responds
      to ETr by a decrease in its UCP3 content.

PMID- 12794175
TI  - The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation
      with membrane properties in rat nociceptive primary afferent neurons.
AB  - We have examined the distribution of the sensory neuron-specific Na+ channel
      Nav1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG)
      neurons and whether its distribution is related to neuronal membrane properties.
      Nav1.8-like immunoreactivity (Nav1.8-LI) was examined with an affinity purified
      polyclonal antiserum (SNS11) in rat DRG neurons that were classified according to
      sensory receptive properties and by conduction velocity (CV) as C-, Adelta- or
      Aalpha/beta. A significantly higher proportion of nociceptive than low threshold
      mechanoreceptive (LTM) neurons showed Nav1.8-LI, and nociceptive neurons had
      significantly more intense immunoreactivity in their somata than LTM neurons.
      Results showed that 89, 93 and 60% of C-, Adelta- and Aalpha/beta-fibre
      nociceptive units respectively and 88% of C-unresponsive units were positive. C
      unresponsive units had electrical membrane properties similar to C-nociceptors
      and were considered to be nociceptive-type neurons. Weak positive Nav1.8-LI was
      also present in some LTM units including a C LTM, all Adelta LTM units (D hair),
      about 10% of cutaneous LTM Aalpha/beta-units, but no muscle spindle afferent
      units. Nav1.8-LI intensity was negatively correlated with soma size (all neurons)
      and with dorsal root CVs in A- but not C-fibre neurons. Nav1.8-LI intensity was
      positively correlated with action potential (AP) duration (both rise and fall
      time) in A-fibre neurons and with AP rise time only in positive C-fibre neurons.
      It was also positively correlated with AP overshoot in positive neurons. Thus
      high levels of Nav1.8 protein may contribute to the longer AP durations
      (especially in A-fibre neurons) and larger AP overshoots that are typical of
      nociceptors.

PMID- 12794176
TI  - Inspiration-promoting vagal reflex in anaesthetized rabbits after rostral
      dorsolateral pons lesions.
AB  - The centrally generated respiratory rhythm is under strong modulation by
      peripheral information, such as that from the slowly adapting pulmonary stretch
      receptors (SA-PSRs) conveyed via the vagus nerve. We have already demonstrated
      that vagal afferent stimulation at a low frequency (5-40 Hz), or holding the lung
      volume at the end-expiratory level (no-inflation test) prevents spontaneous
      termination of the inspiratory (I) phase or initiates I activity in anaesthetized
      rabbits in which the NMDA receptors (NMDA-Rs) are pharmacologically blocked. Here
      we show that this I-promoting vagal reflex also becomes manifest in animals where
      the pontine respiratory groups are ablated. Following lesions of the rostral
      dorsolateral pons, including the nucleus parabrachialis medialis and Kolliker
      Fuse nucleus, with radio-frequency current or local injection of kainic acid, low
      frequency stimulation of the vagus nerve and the no-inflation test significantly
      prolonged the I phase in a manner highly similar to that observed in rabbits with
      NMDA-R block. Brief stimuli at low frequency during the mid-expiratory (E) phase
      evoked I discharge with a latency significantly smaller and less variable than
      that before the lesions. It is concluded that low-frequency input from the SA-PSR
      suppresses I-to-E phase transition and promotes central I activity when the
      medullary respiratory network is released from pontine influence, which involves
      NMDA-R-mediated signalling.

PMID- 12794177
TI  - Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C
      and mitogen-activated protein kinase.
AB  - Intramuscular triacylglycerol is an important energy store and is also related to
      insulin resistance. The mobilization of fatty acids from this pool is probably
      regulated by hormone-sensitive lipase (HSL), which has recently been shown to
      exist in muscle and to be activated by both adrenaline and contractions.
      Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating
      the effect of contractions is unknown and was explored in this study. Incubated
      soleus muscles from 70 g male rats were electrically stimulated to perform
      repeated tetanic contractions for 5 min. The contraction-induced activation of
      HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I
      and calphostin C and reduced 50% by the mitogen-activated protein kinase kinase
      (MEK) inhibitor U0126, which also completely blocked extracellular signal
      regulated kinase (ERK) 1 and 2 phosphorylation. None of the inhibitors reduced
      adrenaline-induced HSL activation in soleus muscle. Both phorbol-12-myristate-13
      acetate (PMA), which activates PKC and, in turn, ERK, and caffeine, which
      increases intracellular Ca2+ without eliciting contraction, increased HSL
      activity. Activated ERK increased HSL activity in supernatant from basal but not
      from electrically stimulated muscle. In conclusion, in muscle, PKC can stimulate
      HSL through ERK. Contractions and adrenaline enhance muscle HSL activity by
      different signalling mechanisms. The effect of contractions is mediated by PKC,
      at least partly via the ERK pathway.

PMID- 12794178
TI  - Area 21a of cat visual cortex strongly modulates neuronal activities in the
      superior colliculus.
AB  - We have examined the influence of cortico-tectal projections from one of the
      pattern-processing extrastriate visual cortical areas, area 21a, on the responses
      to visual stimuli of single neurones in the superior colliculi of adult cats. For
      this purpose area 21a was briefly inactivated by cooling to 10 degrees C using a
      Peltier device. Responses to visual stimuli before and during cooling as well as
      after rewarming ipsilateral area 21a were compared. In addition, in a
      subpopulation of collicular neurones we have studied the effects of reversible
      inactivation of ipsilateral striate cortex (area 17, area V1). When area 21a was
      cooled, the temperature of area 17 was kept at 36 degrees C and vice versa. In
      the majority of cases (41/65; 63%), irrespective of the velocity response
      profiles of collicular neurones, inactivation of area 21a resulted in a
      significant decrease in magnitude of responses of neurones in the ipsilateral
      colliculus and only in a small proportion of cells (2/65; 3.1%) was there a
      significant increase in the magnitude of responses. Inactivation of area 21a
      resulted in significant changes in the magnitude of responses of collicular cells
      located not only in the retino-recipient layers but also in the stratum griseum
      intermediale. In most cases, reversible inactivation of area 17 resulted in a
      greater reduction in the magnitude of responses of collicular cells than
      inactivation of area 21a. Reversible inactivation of area 21a also affected the
      direction selectivity indices and length tuning of most collicular cells tested.

PMID- 12794179
TI  - Interstitial cells: involvement in rhythmicity and neural control of gut smooth
      muscle.
AB  - Many smooth muscles display spontaneous electrical and mechanical activity, which
      persists in the absence of any stimulation. In the past this has been attributed
      largely to the properties of the smooth muscle cells. Now it appears that in
      several organs, particularly in the gastrointestinal tract, activity in smooth
      muscles arises from a separate group of cells, known as interstitial cells of
      Cajal (ICC), which are distributed amongst the smooth muscle cells. Thus in the
      gastrointestinal tract, a network of interstitial cells, usually located near the
      myenteric plexus, generates pacemaker potentials that are conducted passively
      into the adjacent muscle layers where they produce rhythmical membrane potential
      changes. The mechanical activity of most smooth muscle cells, can be altered by
      autonomic, or enteric, nerves innervating them. Previously it was thought that
      neuroeffector transmission occurred simply because neurally released transmitters
      acted on smooth muscle cells. However, in several, but not all, regions of the
      gastrointestinal tract, it appears that nerve terminals, rather than
      communicating directly with smooth muscle cells, preferentially form synapses
      with ICC and these relay information to neighbouring smooth muscle cells. Thus a
      set of ICC, which are distributed amongst the smooth muscle cells of the gut, are
      the targets of transmitters released by intrinsic enteric excitatory and
      inhibitory nerve terminals: in some regions of the gastrointestinal tract, the
      same set of ICC also augment the waves of depolarisation generated by pacemaker
      ICC. Similarly in the urethra, ICC, distributed amongst the smooth muscle cells,
      generate rhythmic activity and also appear to be the targets of autonomic nerve
      terminals.

PMID- 12794180
TI  - Interplay between nitric oxide and vasoactive intestinal polypeptide in inducing
      fluid secretion in rat jejunum.
AB  - Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the
      regulation of neuromuscular function in the gut. They are also potent intestinal
      secretogogues that coexist in the enteric nervous system. The aims of this study
      were: (1) to investigate the interaction between NO and VIP in inducing fluid
      secretion in the rat jejunum, and (2) to determine whether the NO effect on
      intestinal fluid movement is neurally mediated. The single pass perfusion
      technique was used to study fluid movement in a 25 cm segment of rat jejunum in
      vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into
      the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole
      (L-NI)) and the VIP antagonist ([4Cl-D-Phe6,Leu17]VIP (VIPa)) on L-arginine
      induced changes in fluid movement, expressed as microl min(-1) (g dry intestinal
      weight)(-1), was determined. In addition, the effect of neuronal blockade by
      tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride
      (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on
      VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption
      in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced
      a significant fluid secretion (-14 (-20 to -5); P<0.01). This effect was reversed
      completely by L-NAME (60 (36-65); P<0.01) and L-NI (46 (39-75); P<0.01) and
      partially by VIPa (37 (14-47); P<0.01). TTX and BAC partially inhibited the
      effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P<0.05). The
      effect of VIP on fluid movement (-23 (-26 to -14)) was partially reversed by L
      NAME (24 (8.4-35.5); P<0.01) and L-NI (29 (4-44); P<0.01). The inhibition of VIP
      or NO synthase prevented L-arginine- and VIP-induced intestinal fluid secretion
      through a neural mechanism. The data suggest that NO enhances the release of VIP
      from nerve terminals and vice versa. Subsequently, each potentiates the other's
      effect in inducing intestinal fluid secretion.

PMID- 12794182
TI  - IL-6 gene expression in human adipose tissue in response to exercise--effect of
      carbohydrate ingestion.
AB  - Interleukin-6 (IL-6) is a cytokine involved in a number of immunological
      processes, but it is also linked to exercise and possibly energy status. During
      exercise, muscle IL-6 mRNA levels and plasma IL-6 levels are increased and
      further augmented when intramuscular glycogen levels are low. In contrast, the
      increase in plasma IL-6 is blunted if carbohydrate is administered, indicating a
      substrate-regulated induction of IL-6 in human skeletal muscle. Recent studies
      have demonstrated that IL-6 is also released from adipose tissue in response to
      an exercise bout. Furthermore, IL-6 has been demonstrated to have a lipolytic
      effect, thus possibly playing a role in mobilisation of energy as free fatty
      acids (FFA) in response to exercise. The purpose of the present study was to
      investigate the gene expression pattern of IL-6 in adipose tissue in response to
      exercise, and to determine whether gene expression was affected by the ingestion
      of carbohydrate. Eight male subjects performed 3 h of bicycling with ingestion of
      a carbohydrate drink or placebo. Fat biopsy samples and blood samples were
      obtained before, during and in the recovery phase of exercise. Both plasma IL-6
      and adipose IL-6 mRNA levels increased in response to exercise. IL-6 gene
      expression was lower (P<0.05) in the CHO trial (1.98-fold increase, confidence
      interval (CI) 1.16-3.83) compared with the control (6.49-fold increase, CI 3.57
      13.91) at end of exercise. Furthermore, CHO ingestion blunted the increase in
      plasma IL-6 levels (P<0.05) at end of exercise (26.0+/-3.7 pg ml(-1) in the
      control vs. 15.6+/-2.4 pg ml(-1) in the CHO trial). In conclusion, exercise
      results in an increase in IL-6 gene expression in adipose tissue in response to
      exercise, an effect that is significantly blunted by ingestion of carbohydrate.

PMID- 12794184
TI  - Synthetic small molecules that control stem cell fate.
AB  - In an attempt to better understand and control the processes that regulate stem
      cell fate, we have set out to identify small molecules that induce neuronal
      differentiation in embryonic stem cells (ESCs). A high-throughput phenotypic cell
      based screen of kinase-directed combinatorial libraries led to the discovery of
      TWS119, a 4,6-disubstituted pyrrolopyrimidine that can induce neurogenesis in
      murine ESCs. The target of TWS119 was shown to be glycogen synthase kinase-3beta
      (GSK-3beta) by both affinity-based and biochemical methods. This study provides
      evidence that GSK-3beta is involved in the induction of mammalian neurogenesis in
      ESCs. This and such other molecules are likely to provide insights into the
      molecular mechanisms that control stem cell fate, and may ultimately be useful to
      in vivo stem cell biology and therapy.

PMID- 12794181
TI  - Transient and sustained types of long-term potentiation in the CA1 area of the
      rat hippocampus.
AB  - Synaptic potentiation induced by high frequency stimulation was investigated by
      recording field excitatory postsynaptic potentials (f-EPSPs) in rat hippocampal
      slices. Potentiation consisted of a transient period of decaying f-EPSPs (short
      term potentiation, STP) that led to a plateau of continuously potentiated f-EPSPs
      (long-term potentiation, LTP). Here we show that a previously unknown type of
      transient, use-dependent, long-lasting potentiation (t-LTP) can account for STP.
      t-LTP could be stored for more than 6 h and its decay was caused by synaptic
      activation. Both the expression and the decay of t-LTP were input specific. t-LTP
      was induced differently from conventional LTP in that the amplitude of t-LTP was
      dependent upon the stimulation frequency, whereas the magnitude of LTP was
      dependent on the number of stimuli in the induction train. The decay of t-LTP
      could not be prevented by the blockage of glutamate receptors, but was prevented
      by the blockage of stimulus-evoked neurotransmitter release, suggesting that t
      LTP is expressed presynaptically. Paired-pulse stimulation experiments showed
      that the decay of t-LTP was mediated by a decrease in the probability of
      neurotransmitter release. The decline of t-LTP could be prolonged by the
      activation of NMDA receptors. Hence, both single and paired-pulse stimuli
      prolonged the decline of the t-LTP. This decline could be prevented by high
      frequency burst stimulation (200 Hz). We conclude that t-LTP allows dynamic
      modulation of synaptic transmission by providing not only spatial association but
      also temporal convergence between synaptic inputs. Therefore, t-LTP might be a
      substrate for the encoding of synaptic memory.

PMID- 12794185
TI  - Genera of the human lineage.
AB  - Human fossils dated between 3.5 and nearly 7 million years old discovered during
      the last 8 years have been assigned to as many as four new genera of the family
      Hominidae: Ardipithecus, Orrorin, Kenyanthropus, and Sahelanthropus. These
      specimens are described as having morphological traits that justify placing them
      in the family Hominidae while creating a new genus for the classification of
      each. The discovery of these fossils pushed backward by >2 million years the date
      of the oldest hominids known. Only two or three hominid genera, Australopithecus,
      Paranthropus, and Homo, had been previously accepted, with Paranthropus
      considered a subgenus of Australopithecus by some authors. Two questions arise
      from the classification of the newly discovered fossils: (i) Should each one of
      these specimens be placed in the family Hominidae? (ii) Are these specimens
      sufficiently distinct to justify the creation of four new genera? The answers
      depend, in turn, on the concepts of what is a hominid and how the genus category
      is defined. These specimens seem to possess a sufficient number of morphological
      traits to be placed in the Hominidae. However, the nature of the morphological
      evidence and the adaptation-rooted concept of what a genus is do not justify the
      establishment of four new genera. We propose a classification that includes four
      well defined genera: Praeanthropus, Ardipithecus, Australopithecus, and Homo,
      plus one tentative incertae sedis genus: Sahelanthropus.

PMID- 12794186
TI  - The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma
      secretase.
AB  - Notch signaling is involved in numerous cell fate decisions in invertebrates and
      vertebrates. The Notch receptor is a type I transmembrane (TM) protein that
      undergoes two proteolytic steps after ligand binding, first by an ADAM (a
      distintegrin and metalloprotease) in the extracellular region, followed by gamma
      secretase-mediated cleavage inside the TM domain. We demonstrate here that the
      murine ligand Delta1 (Dll1) undergoes the same sequence of cleavages, in an
      apparently signal-independent manner. Identification of the ADAM-mediated
      shedding site localized 10 aa N-terminal to the TM domain has enabled us to
      generate a noncleavable mutant. Kuzbanian/ADAM10 is involved in this processing
      event, but other proteases can probably substitute for it. We then show that Dll1
      is part of a high-molecular-weight complex containing presenilin1 and undergoes
      further cleavage by a gamma-secretase-like activity, therefore releasing the
      intracellular domain that localizes in part to the nucleus. Using the shedding
      resistant mutant, we demonstrate that this gamma-secretase cleavage depends on
      prior ectodomain shedding. Therefore Dll1 is a substrate for regulated
      intramembrane proteolysis, and its intracellular region possibly fulfills a
      specific function in the nucleus.

PMID- 12794187
TI  - Sustainability science: the emerging research program.

PMID- 12794188
TI  - RNA processing and degradation in Bacillus subtilis.
AB  - This review focuses on the enzymes and pathways of RNA processing and degradation
      in Bacillus subtilis, and compares them to those of its gram-negative
      counterpart, Escherichia coli. A comparison of the genomes from the two organisms
      reveals that B. subtilis has a very different selection of RNases available for
      RNA maturation. Of 17 characterized ribonuclease activities thus far identified
      in E. coli and B. subtilis, only 6 are shared, 3 exoribonucleases and 3
      endoribonucleases. Some enzymes essential for cell viability in E. coli, such as
      RNase E and oligoribonuclease, do not have homologs in B. subtilis, and of those
      enzymes in common, some combinations are essential in one organism but not in the
      other. The degradation pathways and transcript half-lives have been examined to
      various degrees for a dozen or so B. subtilis mRNAs. The determinants of mRNA
      stability have been characterized for a number of these and point to a
      fundamentally different process in the initiation of mRNA decay. While RNase E
      binds to the 5' end and catalyzes the rate-limiting cleavage of the majority of
      E. coli RNAs by looping to internal sites, the equivalent nuclease in B.
      subtilis, although not yet identified, is predicted to scan or track from the 5'
      end. RNase E can also access cleavage sites directly, albeit less efficiently,
      while the enzyme responsible for initiating the decay of B. subtilis mRNAs
      appears incapable of direct entry. Thus, unlike E. coli, RNAs possessing stable
      secondary structures or sites for protein or ribosome binding near the 5' end can
      have very long half-lives even if the RNA is not protected by translation.

PMID- 12794190
TI  - ADP-glucose pyrophosphorylase, a regulatory enzyme for bacterial glycogen
      synthesis.
AB  - The accumulation of alpha-1,4-polyglucans is an important strategy to cope with
      transient starvation conditions in the environment. In bacteria and plants, the
      synthesis of glycogen and starch occurs by utilizing ADP-glucose as the glucosyl
      donor for elongation of the alpha-1,4-glucosidic chain. The main regulatory step
      takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP
      Glc pyrophosphorylase (PPase). Most of the ADP-Glc PPases are allosterically
      regulated by intermediates of the major carbon assimilatory pathway in the
      organism. Based on specificity for activator and inhibitor, classification of ADP
      Glc PPases has been expanded into nine distinctive classes. According to
      predictions of the secondary structure of the ADP-Glc PPases, they seem to have a
      folding pattern common to other sugar nucleotide pyrophosphorylases. All the ADP
      Glc PPases as well as other sugar nucleotide pyrophosphorylases appear to have
      evolved from a common ancestor, and later, ADP-Glc PPases developed specific
      regulatory properties, probably by addition of extra domains. Studies of
      different domains by construction of chimeric ADP-Glc PPases support this
      hypothesis. In addition to previous chemical modification experiments, the latest
      random and site-directed mutagenesis experiments with conserved amino acids
      revealed residues important for catalysis and regulation.

PMID- 12794191
TI  - Virus entry, assembly, budding, and membrane rafts.
AB  - As intracellular parasites, viruses rely heavily on the use of numerous cellular
      machineries for completion of their replication cycle. The recent discovery of
      the heterogeneous distribution of the various lipids within cell membranes has
      led to the proposal that sphingolipids and cholesterol tend to segregate in
      microdomains called membrane rafts. The involvement of membrane rafts in
      biosynthetic traffic, signal transduction, and endocytosis has suggested that
      viruses may also take advantage of rafts for completion of some steps of their
      replication cycle, such as entry into their cell host, assembly, and budding. In
      this review, we have attempted to delineate all the reliable data sustaining this
      hypothesis and to build some models of how rafts are used as platforms for
      assembly of some viruses. Indeed, if in many cases a formal proof of raft
      involvement in a virus replication cycle is still lacking, one can reasonably
      suggest that, owing to their ability to specifically attract some proteins, lipid
      microdomains provide a particular milieu suitable for increasing the efficiency
      of many protein-protein interactions which are crucial for virus infection and
      growth.

PMID- 12794195
TI  - Surveillance of sexually transmitted infections in primary care.

PMID- 12794196
TI  - New drugs for treating drug resistant HIV-1.

PMID- 12794197
TI  - Central pontine myelinolysis complicating treatment of multicentric Castleman's
      disease and Kaposi's sarcoma in a patient with AIDS.
AB  - An HIV positive black African woman presented with widespread lymphadenopathy and
      pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed
      both Kaposi's sarcoma and multicentric Castleman's disease. Despite
      antiretroviral therapy and chemotherapy the patient deteriorated, developing
      confusion and dysphasia. A cranial magnetic resonance scan showed central pontine
      myelinolysis. Despite supportive therapy the patient died.

PMID- 12794198
TI  - View 1: Assisted conception in couples with HIV infection.

PMID- 12794193
TI  - Conjugative plasmid transfer in gram-positive bacteria.
AB  - Conjugative transfer of bacterial plasmids is the most efficient way of
      horizontal gene spread, and it is therefore considered one of the major reasons
      for the increase in the number of bacteria exhibiting multiple-antibiotic
      resistance. Thus, conjugation and spread of antibiotic resistance represents a
      severe problem in antibiotic treatment, especially of immunosuppressed patients
      and in intensive care units. While conjugation in gram-negative bacteria has been
      studied in great detail over the last decades, the transfer mechanisms of
      antibiotic resistance plasmids in gram-positive bacteria remained obscure. In the
      last few years, the entire nucleotide sequences of several large conjugative
      plasmids from gram-positive bacteria have been determined. Sequence analyses and
      data bank comparisons of their putative transfer (tra) regions have revealed
      significant similarities to tra regions of plasmids from gram-negative bacteria
      with regard to the respective DNA relaxases and their targets, the origins of
      transfer (oriT), and putative nucleoside triphosphatases NTP-ases with homologies
      to type IV secretion systems. In contrast, a single gene encoding a septal DNA
      translocator protein is involved in plasmid transfer between micelle-forming
      streptomycetes. Based on these clues, we propose the existence of two
      fundamentally different plasmid-mediated conjugative mechanisms in gram-positive
      microorganisms, namely, the mechanism taking place in unicellular gram-positive
      bacteria, which is functionally similar to that in gram-negative bacteria, and a
      second type that occurs in multicellular gram-positive bacteria, which seems to
      be characterized by double-stranded DNA transfer.

PMID- 12794199
TI  - View 2: Assisted conception in couples with HIV infection.

PMID- 12794192
TI  - Prophage genomics.
AB  - The majority of the bacterial genome sequences deposited in the National Center
      for Biotechnology Information database contain prophage sequences. Analysis of
      the prophages suggested that after being integrated into bacterial genomes, they
      undergo a complex decay process consisting of inactivating point mutations,
      genome rearrangements, modular exchanges, invasion by further mobile DNA
      elements, and massive DNA deletion. We review the technical difficulties in
      defining such altered prophage sequences in bacterial genomes and discuss
      theoretical frameworks for the phage-bacterium interaction at the genomic level.
      The published genome sequences from three groups of eubacteria (low- and high-G+C
      gram-positive bacteria and gamma-proteobacteria) were screened for prophage
      sequences. The prophages from Streptococcus pyogenes served as test case for
      theoretical predictions of the role of prophages in the evolution of pathogenic
      bacteria. The genomes from further human, animal, and plant pathogens, as well as
      commensal and free-living bacteria, were included in the analysis to see whether
      the same principles of prophage genomics apply for bacteria living in different
      ecological niches and coming from distinct phylogenetical affinities. The effect
      of selection pressure on the host bacterium is apparently an important force
      shaping the prophage genomes in low-G+C gram-positive bacteria and gamma
      proteobacteria.

PMID- 12794200
TI  - Prospective study on cervical neoplasia: presence of HPV DNA in cytological
      smears precedes the development of cervical neoplastic lesions.
AB  - OBJECTIVES: The principal aim of the study was to verify whether HPV infection in
      healthy women, as determined by HPV DNA detection, was associated with an
      increased risk of development of cervical lesions. METHODS: Cervical smears
      collected at enrolment into the prospective study conducted in Prague during 1975
      83 were tested for the presence of HPV DNA by means of a polymerase chain
      reaction (PCR) using the general GP5/6 primers and a mixture of primers specific
      for the E6 gene. 120 smears from patients in whom cervical neoplasia had been
      detected in the course of the prospective study and 208 smears from control women
      who had remained healthy throughout the observation period were analysed.
      Patients and controls were matched by age, number of sexual partners, age at
      first intercourse, and smoking habit. Patients were divided into three groups, A,
      B, and C, according to their cytological, colposcopic, and histological findings
      at enrolment. Group A consisted of 67 women found ill at enrolment, group B of 26
      women with slightly suspicious findings, while group C comprised 27 women with
      normal findings at enrolment. In addition, sera taken at enrolment from these
      patients and controls were tested for the presence of antibodies reactive with
      virus-like particles (VLPs) of HPV 16, 18, and 33. RESULTS: For the whole cohort,
      there was a statistically highly significant difference in the presence of HPV
      DNA between patients and controls. Furthermore, the difference in the presence of
      HPV DNA between patients and controls was highly significant not only in those
      who had been found ill at enrolment (group A) but, most importantly, also in
      women who had developed the disease in the course of the follow up (groups B and
      C). Women positive for HPV DNA possessed HPV antibodies to VLP16, 18 and 33
      significantly more often than those who were free of HPV DNA. CONCLUSION: This
      indicated that healthy women who were positive for HPV DNA at enrolment were at
      an increased risk of developing cervical neoplasia (OR = 18.5; CI 5.9 to 57.6).

PMID- 12794201
TI  - Avoiding risky sex partners: perception of partners' risks v partners' self
      reported risks.
AB  - BACKGROUND: Key strategies advocated for lowering personal risk of sexual
      exposure to STD/HIV include having fewer partners and avoiding risky partners.
      However, few studies have systematically examined how well people can actually
      discern their sex partners' risk behaviours. METHODS: We conducted face to face
      interviews with 151 heterosexual patients with gonorrhoea or chlamydial infection
      and 189 of their sex partners. Interviews examined the patients' perceptions of
      their sex partners' sociodemographic characteristics and risk behaviours.
      Patients' perceptions of partners were then sociometrically compared for
      agreement with partner self reports, using the kappa statistic for discrete
      variables and concordance correlation for continuous variables. RESULTS:
      Agreement was highest for perceived partner age, race/ethnicity, and duration of
      sexual partnership; and lowest for knowledge of partner's work in commercial sex,
      number of other sex partners, and for perceived quality of communication within
      the partnership. Index patients commonly underestimated or overestimated
      partners' risk characteristics. Reported condom use was infrequent and
      inconsistent within partnerships. CONCLUSION: Among people with gonorrhoea or
      chlamydial infection, patients' perceptions of partners' risk behaviours often
      disagreed with the partners' self reports. Formative research should guide
      development and evaluation of interventions to enhance sexual health
      communication within partnerships and within social networks, as a potential harm
      reduction strategy to foster healthier partnerships.

PMID- 12794189
TI  - Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus
      8) epidemiology and pathogenesis.
AB  - Kaposi's sarcoma had been recognized as unique human cancer for a century before
      it manifested as an AIDS-defining illness with a suspected infectious etiology.
      The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as
      human herpesvirus-8, in 1994 by using representational difference analysis, a
      subtractive method previously employed for cloning differences in human genomic
      DNA, was a fitting harbinger for the powerful bioinformatic approaches since
      employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was
      rapidly followed by publication of its complete sequence, which revealed that the
      virus had coopted a wide armamentarium of human genes; in the short time since
      then, the functions of many of these viral gene variants in cell growth control,
      signaling apoptosis, angiogenesis, and immunomodulation have been characterized.
      This critical literature review explores the pathogenic potential of these genes
      within the framework of current knowledge of the basic herpesvirology of KSHV,
      including the relationships between viral genotypic variation and the four
      clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods
      and their utility, primary infection by KSHV, tissue culture and animal models of
      latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation
      from latency. Recent advances in models of de novo endothelial infection,
      microarray analyses of the host response to infection, receptor identification,
      and cloning of full-length, infectious KSHV genomic DNA promise to reveal key
      molecular mechanisms of the candidate pathogeneic genes when expressed in the
      context of viral infection.

PMID- 12794202
TI  - Increasing relative prevalence of HSV-2 infection among men with genital ulcers
      from a mining community in South Africa.
AB  - OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its
      association with HIV infection in the mining community of Carletonville, South
      Africa, from two cross sectional surveys of consecutive men presenting with
      genital lesions during October 1993 to January 1994 and July to November 1998.
      METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with
      amplicon detection was used to identify DNA specific sequences of Treponema
      pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR
      assay was used to differentiate between HSV-1 and HSV-2. RESULTS: M-PCR detected
      T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients
      during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The
      proportion of patients with more than one agent increased significantly from 7.3%
      (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a
      higher proportion of ulcer specimens from HIV infected patients than in specimens
      from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p
      <0.001; 1998: 42.1% v 29.6%, p >0.09). CONCLUSIONS: Based on two cross sectional
      surveys, 4 years apart, chancroid remained the leading cause of GUD in men who
      presented at the STD clinic with genital ulcers in the mining community of
      Carletonville, South Africa. The relative prevalence of primary syphilis has
      remained low. However, HSV-2 has emerged as a more significant cause of GUD and
      the proportion of GUD patients infected with more than one agent also increased
      significantly. HSV-2 DNA was detected in a significantly higher proportion of
      ulcer specimens from HIV positive patients than from HIV negative patients. No
      association was found between HIV infection status and the relative prevalence of
      chancroid or syphilis.

PMID- 12794203
TI  - Impact of on-site testing for maternal syphilis on treatment delays, treatment
      rates, and perinatal mortality in rural South Africa: a randomised controlled
      trial.
AB  - BACKGROUND: Syphilis remains a significant cause of preventable perinatal death
      in developing countries, with many women remaining untested and thus untreated.
      Syphilis testing in the clinic (on-site testing) may be a useful strategy to
      overcome this. We studied the impact of on-site syphilis testing on treatment
      delays and rates, and perinatal mortality. METHODS: We conducted a cluster
      randomised controlled trial among seven pairs of primary healthcare clinics in
      rural South Africa, comparing on-site testing complemented by laboratory
      confirmation versus laboratory testing alone. Intervention clinics used the on
      site test conducted by primary care nurses, with results and treatment available
      within an hour. Control clinics sent blood samples to the provincial laboratory,
      with results returned 2 weeks later. RESULTS: Of 7134 women seeking antenatal
      care with available test results, 793 (11.1%) tested positive for syphilis. Women
      at intervention clinics completed treatment 16 days sooner on average (95%
      confidence interval: 11 to 21), though there was no significant difference in the
      proportion receiving adequate treatment at intervention (64%) and control (69%)
      clinics. There was also no significant difference in the proportion experiencing
      perinatal loss (3.3% v 5.1%; adjusted risk difference: -0.9%; 95% CI -4.4 to
      2.7). CONCLUSIONS: Despite reducing treatment delays, the addition of on-site
      syphilis testing to existing laboratory testing services did not lead to higher
      treatment rates or reduce perinatal mortality. However on-site testing for
      syphilis may remain an important option for improving antenatal care in settings
      where laboratory facilities are not available.

PMID- 12794206
TI  - Female genital mutilation in the Sudan: survey of the attitude of Khartoum
      university students towards this practice.
AB  - BACKGROUND: Female genital mutilation (FGM) or female circumcision is the removal
      of variable amounts of tissue from the female external genitalia. It is practised
      all over the world on very young girls. This study was conducted in Sudan where
      FGM is a criminal offence and not a religious dictate. We assessed the knowledge,
      attitudes, and perceptions of this practice among Khartoum university students
      and compared the differences between male and female student responses. METHODS:
      An anonymised detailed questionnaire was distributed among the university
      students. In addition to the participant's age, marital status, course studying,
      details regarding their attitude, knowledge of the practice of FGM, and their own
      experiences were collected. RESULTS: Of the 500 questionnaires distributed, 414
      (82.8%) were returned from 192 (46%) females and 222 (54%) males. 109 (56.8%) of
      the female respondents were themselves circumcised.18.8% of the male students and
      9.4% of the female students thought FGM was recommended by their religion. Only
      90 (46.9%) female students compared with 133 (59.9%) male students thought FGM
      was illegal. Though 16 (8.3%) female respondents thought FGM would increase their
      chances of marriage, the majority, 166 (74.8%), of the male students would prefer
      a non-circumcised female. CONCLUSIONS: This study shows that 109 (56.8%) female
      university students who responded were circumcised. Confusing religious messages
      and ambiguous laws seem to be responsible for the continuation of this practice.
      The study highlights the partnership that needs to be established between
      religious leaders and educationalists to end this medieval practice.

PMID- 12794204
TI  - Male circumcision: an acceptable strategy for HIV prevention in Botswana.
AB  - BACKGROUND: Male circumcision is known to reduce the risk of acquiring HIV, but
      few studies have been performed to assess its acceptability among either children
      or adults in sub-Saharan Africa. METHODS: We conducted a cross sectional survey
      in nine geographically representative locations in Botswana to determine the
      acceptability of male circumcision in the country, as well as the preferred age
      and setting for male circumcision. Interviews were conducted using standardised
      questionnaires both before and after an informational session outlining the risks
      and benefits of male circumcision. RESULTS: Among 605 people surveyed, the median
      age was 29 years (range 18-74 years), 52% were male, and >15 ethnicities were
      represented. Before the informational session, 408 (68%) responded that they
      would definitely or probably circumcise a male child if circumcision was offered
      free of charge in a hospital setting; this number increased to 542 (89%) after
      the informational session. Among 238 uncircumcised men, 145 (61%) stated that
      they would definitely or probably get circumcised themselves if it were offered
      free of charge in a hospital setting; this increased to 192 (81%) after the
      informational session. In a multivariate analysis of all participants, people
      with children were more likely to favour circumcision than people without
      children (adjusted odds ratio 1.8, 95% CI 1.0 to 3.4). Most participants (55%)
      felt that the ideal age for circumcision is before 6 years, and 90% of
      participants felt that circumcision should be performed in the hospital setting.
      CONCLUSIONS: Male circumcision appears to be highly acceptable in Botswana. The
      option for safe circumcision should be made available to parents in Botswana for
      their male children. Circumcision might also be an acceptable option for adults
      and adolescents, if its efficacy as an HIV prevention strategy among sexually
      active people is supported by clinical trials.

PMID- 12794207
TI  - Diagnosis and treatment of presumed STIs at Mexican pharmacies: survey results
      from a random sample of Mexico City pharmacy attendants.
AB  - OBJECTIVES: People in developing countries often seek medical advice for common
      ailments from pharmacies. As one example, pharmacists routinely diagnose and
      treat symptomatic sexually transmitted infections (STIs). We aimed to assess the
      quality of advice provided in Mexico City pharmacies by presenting hypothetical
      STI related syndromes and recording pharmacy attendants' suggested diagnoses and
      treatments. METHODS: We interviewed the first available attendant in each of a 5%
      random sample of Mexico City's pharmacies. We inquired about the training, age,
      and experience of the attendant and about the typical number of clients coming
      for treatment of suspected STIs. After considering three hypothetical case
      studies, attendants recommended diagnoses, treatments, and, sometimes, physician
      follow up. RESULTS: Most Mexico City "pharmacists" are actually clerks, with
      trained pharmacists rarely available on the premises. The average pharmacy
      attendant was 32 years old, with a median of 5 years' experience at that
      pharmacy, but very limited (if any) training. 62% reported seeing 10 or more
      clients with genital or vaginal infections per month. Depending on the case
      study, attendants provided appropriate diagnoses in 0-12% of cases, recommended
      appropriate treatments in 12-16% of cases, and suggested physician follow up for
      26-67% of cases. CONCLUSIONS: In general, surveyed pharmacy personnel were unable
      to diagnose accurately or offer appropriate treatment advice when presented with
      classic, common STI symptoms. Given the volume of clients seeking advice from
      this source, training pharmacy attendants could significantly help to reduce the
      burden of disease associated with STIs in Mexico City.

PMID- 12794209
TI  - Urine based screening for asymptomatic/undiagnosed genital chlamydial infection
      in young people visiting the accident and emergency department is feasible,
      acceptable, and can be epidemiologically helpful.
AB  - OBJECTIVE: To assess the acceptability and the feasibility of urine based
      Chlamydia trachomatis screening in asymptomatic young people aged 16-35 years
      attending an inner city accident and emergency (A&E) department. DESIGN: Cross
      sectional study. SETTING: A&E department in a teaching hospital, in south London,
      UK. METHOD: From July to November 2001 a urine based chlamydia screening test was
      offered to 719 consecutive A&E attendees aged 16-35 years and their companions.
      Participants were given an information sheet and were asked to complete a
      demographic and sexual health questionnaire. Following informed consent, eligible
      participants provided first pass urine specimens. Specimens were tested for C.
      trachomatis using nucleic acid amplification. RESULTS: Of the A&E attendees
      asked, 76.5% (550/719) agreed to participate. Prevalence of genital chlamydial
      infection was 4.2% (18/432; 95% confidence interval (CI) 2.5 to 6.6). 12 of the
      positive participants (66.7%; 95% CI 40.99 to 86.65) were women, of whom seven
      were Afro-Caribbean. Nine of the chlamydia positive participants (50%; 95% CI
      26.0 to 73.9) were aged 25 years. Three of the positive urine specimens were from
      companions, of whom a total of 143 were screened. All the positive participants
      were contactable, and were offered treatment. CONCLUSION: Urine based screening
      for undiagnosed genital chlamydial infection in the A&E department was acceptable
      and feasible. The department provides a unique site for screening young patients
      and companions, men and women.

PMID- 12794210
TI  - Who is being tested for genital chlamydia in primary care?
AB  - OBJECTIVES: To explore current patterns of testing for genital chlamydial
      infection in primary care, and to identify practice characteristics influencing
      testing rates. METHOD: Aggregate numbers of chlamydia tests and results for each
      practice in Nottingham Health District were matched to practice characteristics.
      Age specific testing rates and diagnosed prevalence were calculated, and
      characteristics of the practice tested for association with chlamydia testing
      rates. RESULTS: Most tests (63.1%) were performed on women over the age of 25,
      but the proportion of positive tests was highest in 15-19 year olds (13.3%)
      followed by 20-24 year olds (8.2%). A higher ratio of GP principals to female
      practice population was associated with higher testing rates and more chlamydia
      isolations, but the ratio of female GP principals to patients was associated with
      higher testing rates only in 20-24 year olds. Diagnosed incidence was greatest in
      more socioeconomically deprived practice populations, and this was not explained
      by higher testing rates. Men were rarely tested. CONCLUSION: Current testing
      practice in primary care does not reflect the known epidemiology of genital
      chlamydia infection. Practices with lower doctor-patient ratios do less testing,
      and measures to enable their active participation in the envisaged screening
      programme will be important in reaching all at-risk groups.

PMID- 12794211
TI  - Correlation between culture testing of swabs and ligase chain reaction of first
      void urine from patients recently treated for Chlamydia trachomatis.
AB  - We assessed the correlation between ligase chain reaction (LCR) on first void
      urine (FVU) and cultures of urethral and cervical swabs to detect chlamydia
      during three post-treatment follow up visits for 10 men and 19 women with genital
      chlamydial infections who had been treated with azithromycin or doxcycline.

PMID- 12794213
TI  - Use of a leaflet to replace verbal pretest discussion for HIV: effects and
      acceptability.
AB  - OBJECTIVE: To determine the effect of using a leaflet to replace formal verbal
      pretest discussion and assess its acceptability to patients. SETTING AND METHODS:
      A leaflet was developed which gave information on all routine tests undertaken at
      a genitourinary medicine clinic. Information normally given during verbal pretest
      discussion for HIV was included. The leaflet was given to all new attenders at
      routine STI clinics. The proportion of patients accepting tests in the 6 weeks
      before and 4 weeks after the introduction of the leaflet was elicited by case
      note review. The acceptability of the leaflet was determined by means of a
      questionnaire given to patients. RESULTS: The use of the leaflet increased the
      number of patients offered an HIV test from 654 of 1004 (65%) patients to 371 of
      397 (94%), p<0.001. It also increased the number tested from 325 (32%) of 1004
      patients to 210 of 397 (53%, p<0.001). Men were more likely to be offered an HIV
      test than women at baseline (342 of 500 men, 68%, v 312 of 504 women, 62%,
      p=0.036) but after the intervention there was no longer a difference (men 217,
      93%, female 154, 94%). The number of men accepting a test increased more than the
      number of women (139 of 233 men, 60%, 71 of 164 women, 43%, p <0.005). The 79
      questionnaires suitable for analysis showed patient views on the leaflet were
      mainly favourable: easy to understand 73 (92%), clear 70 (89%), absence of
      difficult words 73 (91%), and right balance of information 68 (86%). CONCLUSIONS:
      The routine use of a leaflet to replace verbal pretest discussion (PTD) increased
      the proportion of patients undergoing testing. Part of the increased testing was
      because physicians were more likely to offer the test, possibly because the time
      constraints of pretest discussion were removed. This appears to be an acceptable
      and effective way of increasing HIV testing in GUM clinics but further work is
      needed to elicit information on non-responders to the questionnaire.

PMID- 12794212
TI  - Variation in clinical practice in genitourinary medicine clinics in the United
      Kingdom.
AB  - OBJECTIVES: This study was conducted to examine the variation in clinical
      practice in genitourinary medicine clinics in the United Kingdom in early 2002.
      METHODS: Questionnaires were sent to all 234 consultants in charge of
      genitourinary medicine clinics in the United Kingdom in March-May 2002. The
      questions concerned clinical practice in respect of asymptomatic patients
      presenting for an infection screen, and practice in respect of some specific
      sexually transmitted and other genitourinary infections. RESULTS: The test for
      infection least likely to be offered to heterosexuals is an HIV test (71% and 70%
      of clinics routinely offer this to male and female heterosexuals respectively).
      The practice of permitting "low risk" patients to telephone for their HIV results
      now extends to 24% of clinics. 34% of clinics do not require patients with non
      specific urethritis to attend for follow up. 41% of clinics routinely ask
      patients treated for Chlamydia trachomatis to return for a follow up chlamydia
      detection test. 25% of clinics routinely offer two tests of cure to all patients
      with gonorrhoea. 6% of clinics do not routinely offer syphilis serology to
      heterosexuals. Other significant variations in clinical practice were documented.
      CONCLUSIONS: Overall, our findings indicate the need for further evidence to
      guide clinical practice and a wider knowledge and debate of national guidelines.

PMID- 12794214
TI  - Group B streptococcus carriage and vulvovaginal symptoms: causal or casual? A
      case-control study in a GUM clinic population.
AB  - OBJECTIVES: The isolation of group B streptococcus (GBS) on routine swabs taken
      from genitourinary medicine (GUM) clinic attendees is a common finding. The
      relation of GBS to vulvovaginal symptoms is unclear, creating confusion about
      management. This case-control study tested the hypothesis that detection of GBS
      on routine clinical specimens is not causally related to vulvovaginal symptoms in
      female GUM clinic attendees. METHODS: Data were collected on all female GUM
      clinic attendees who had GBS isolated from anogenital swabs between July 1999 and
      July 2001. Controls were randomly selected from all new and rebooking female GUM
      clinic attendees. Controls were group matched for age with cases and were
      included only if a sexual health screen was performed and the results of this
      were available. RESULTS: 118 cases and 308 controls were identified during the
      study period. There was no significant difference between cases and controls in
      patient demographic or behavioural characteristics, the presence of genital co
      infection, or vulvovaginal symptoms. There was no relation between symptoms and
      quantitative growth of GBS reported by the laboratory in either cervical or
      urethral swabs. Only nine cases had high vaginal swabs taken, in whom there was a
      significant association between a heavy growth of GBS and vulvovaginal symptoms
      (p=0.008). CONCLUSION: The isolation of GBS from routinely collected genital
      swabs in female attendees of a GUM clinic is not causally related to vulvovaginal
      symptoms. We recommend that patients should receive this advice and should not be
      treated with antibiotic therapy for this indication.

PMID- 12794215
TI  - Vulvovaginal carriage of yeasts other than Candida albicans.
AB  - AIMS: We investigated the spectrum of yeasts isolated, and compared the
      epidemiological and laboratory characteristics of women carrying vulvovaginal
      Candida albicans with those carrying yeasts other than C. albicans. METHOD:
      Between April and June 2001, 5802 consecutively received genital swabs from women
      were plated onto Candida ID chromogenic media (BioMerieux). Blue colonies were
      reported as C. albicans; all other colonies (white and pink) were identified to
      species level using the Vitek YBC card (BioMerieux). In vitro susceptibility to
      amphotericin (AMB), fluconazole (FLU), itraconazole (ITZ), and voriconazole (VOR)
      was determined for approximately 40% of non-C. albicans yeasts using a
      standardised microdilution method. RESULTS: Yeast was isolated from 1221 women
      (21%). Of these, C. albicans only was isolated from 1087 (89%) and yeasts other
      than C. albicans from 129 (11%) women. C. glabrata comprised 89 (69%) of the
      latter. Women in whom other yeasts were recovered were older than those with C.
      albicans (mean 43, versus 33 years, p <0.001). All isolates tested (n=53) were
      susceptible to AMB and VOR. Seven (24%) C. glabrata strains were susceptible to
      FLU with 21 (72%) testing susceptible-dose dependent. CONCLUSION: Yeasts other
      than C. albicans are common vaginal isolates even in a primary care population.
      The species isolated are less susceptible to FLU than most C. albicans.

PMID- 12794216
TI  - The reliability of a structured examination protocol and self administered
      vaginal swabs: a pilot study of gynaecological outpatients in Goa, India.
AB  - OBJECTIVES: Low participation rates for gynaecological examination and low
      reliability of clinical reporting of gynaecological examination findings are
      problems in community studies of gynaecological morbidity in India. This pilot
      study aimed to describe the reliability of a new examination protocol for
      recording the findings of gynaecological examination and the reliability and
      acceptability of the use of self administered vaginal swabs for the diagnosis of
      reproductive tract infections. METHOD: 75 women attending a gynaecology
      outpatient clinic were purposively sampled. Each woman was examined by two
      gynaecologists independently who recorded findings on the new examination
      protocol. Two swabs were collected from each woman, one by the gynaecologist and
      one by the woman. Swabs were smeared on separate slides which were stained and
      read for bacterial vaginosis and candidiasis by laboratory technicians blind to
      the mode of collection of the slides. RESULTS: The study showed a high inter
      rater reliability for most of the items of the examination protocol. The
      interslide agreement for the diagnosis of the two RTIs was high. One third of
      women preferred the self administered swab. CONCLUSIONS: The examination protocol
      is a reliable method of recording gynaecological examination findings, and self
      administered swabs a useful way of obtaining vaginal specimens from women who did
      not wish to undergo gynaecological examinations in studies in the Indian setting.

PMID- 12794217
TI  - National survey of doctors' actions following the diagnosis of a bacterial STD.
AB  - OBJECTIVES: Little is known about the post-STD diagnosis management practices of
      community based doctors. The purpose of this study was to describe the reported
      actions that doctors take after diagnosing gonorrhoea, chlamydia, or syphilis and
      to determine if these actions differ across the three STDs. METHODS: A random
      national sample of 7300 doctors (70% response rate) practising in five medical
      specialties responded to 13 questions related to STD management. Mean differences
      across STDs were examined using the General Linear Model function of SPSS.
      RESULTS: Most doctors reported instructing patients to abstain from sex during
      treatment, to use condoms, and to inform their sexual partners of their exposure
      after diagnosing gonorrhoea, chlamydia, or syphilis. For syphilis, however,
      doctors were less likely to treat the patients presumptively and to give them
      drugs for their partners; and more likely to collect partner information, to
      follow up with the patient to see if the partner was referred for treatment and
      to send patient information to the health department. CONCLUSIONS: Doctors' post
      STD diagnosis actions were similar for gonorrhoea and chlamydia compared to
      syphilis. Study findings suggest low levels of STD case reporting and partner
      follow up by doctors in the sample. Interventions are needed to educate community
      based doctors about the importance of partner follow up and case reporting in the
      management of STDs.

PMID- 12794218
TI  - Is increased surveillance for asymptomatic syphilis in an HIV outpatient
      department worthwhile?
AB  - OBJECTIVES: Syphilis outbreaks have recently been reported in the United Kingdom,
      some of which have included cohorts of HIV positive individuals. As a result we
      commenced 3 monthly screening of syphilis serology (STS) for HIV positive
      patients having routine follow up blood tests. We assessed if there was an
      increased number of individuals being screened and also whether the screening
      programme was diagnosing early cases of syphilis. METHODS: Data from a 1 year
      period following introduction of screening (May 2001) were analysed and compared
      with data from the same period last year. The case notes of patients with a
      positive VDRL were reviewed to establish, firstly, whether these represented new
      diagnoses and, secondly, whether patients were asymptomatic at the time of
      screening. RESULTS: 2670 patients had at least one CD4 count measured in the
      period (surrogate for patients having routine bloods). Of these, 2266 patients
      had STS performed (85%). 38 patients had a positive VDRL. Of these, 20 were
      confirmed as having early syphilis which was asymptomatic at the time of
      screening. Six asymptomatic cases were also confirmed with newly positive TPPAs
      and a negative VDRL. These 26 asymptomatic cases represent 29% of all cases of
      early syphilis diagnosed in our department and 50% of cases in the HIV positive
      cohort. CONCLUSION: With intensive surveillance significant numbers of cases of
      asymptomatic early syphilis are being identified in a group of HIV individuals
      under routine follow up, at an earlier stage than would otherwise have been the
      case. This presents an opportunity to intervene not only to prevent clinical
      illness but also to institute infection control measures.

PMID- 12794221
TI  - Superior mesenteric artery syndrome in an HIV positive patient.

PMID- 12794219
TI  - Late recurrence of resistant Trichomonas vaginalis vaginitis: relapse or re
      infection?
AB  - Distinguishing between re-infection and relapse of trichomonas infections is
      often a difficult task in the clinical setting. The chronicity of trichomonas
      infections and the ongoing sexual activity are two confounding factors. We
      present a patient with recurrent resistant vaginal trichomoniasis shortly
      following a sexual contact with an untreated partner after a complete response to
      treatment with tinidazole for nine months. We hypothesise that re-infection
      occurred from the asymptomatic partner who was an untreated chronic carrier of
      resistant trichomonas in the urogenital tract.

PMID- 12794222
TI  - Perforating chancre: any cause-effect relation with HIV infection?

PMID- 12794223
TI  - The HIV/AIDS epidemic in Ukraine: stable or still exploding?

PMID- 12794224
TI  - Was the Papanicolaou smear responsible for the decline of Trichomonas vaginalis?

PMID- 12794225
TI  - Partner notification in primary care.

PMID- 12794226
TI  - Raising awareness of UK GUM clinic activities.

PMID- 12794227
TI  - Treatment of Candida glabrata using topical amphotericin B and flucytosine.

PMID- 12794228
TI  - Circumcision in genital warts--let us not forget!

PMID- 12794229
TI  - Clinical applications of body composition measurements using DXA.
AB  - Dual-energy X-ray absorptiometry (DXA) scanning was primarily developed for the
      diagnosis of osteoporosis and was initially applied to studies of the clinically
      important sites of the lumbar spine, femoral neck, and forearm. The rapid
      adoption of DXA has led to the development of different, competing generations of
      equipment. Improvements have been achieved through advances in X-ray generation
      and detection technology, modification of data acquisition protocols, and
      implementation of more sophisticated image analysis algorithms. As a result, DXA
      has been extended to allow the study of the total skeleton and its regional
      parts, as well as soft-tissue composition measurement. The three major components
      of the body: fat mass, lean mass, and bone mineral mass, can now be easily
      measured using a single whole body DXA scan with high precision and low scanning
      time. The comprehensive view of body composition provided by DXA makes it an
      attractive technique for a variety of clinical applications such as the
      prevention of cardiovascular and metabolic diseases, clinical management of
      different chronic diseases, and monitoring of the impact of treatment regimens on
      body tissues. In this article we review the contribution DXA has made to the
      understanding of body composition in clinical studies in adults.

PMID- 12794230
TI  - Standardization of BMD T-Scores in the first five years after the menopause: do
      femoral neck-equivalent and older normative range T-Scores improve diagnostic
      agreement?
AB  - Calculating T-scores using an older reference population reduces inconsistency
      between measurement sites when osteoporosis is diagnosed in the elderly. The
      present analysis in a younger, early postmenopausal cohort examined 5-yr
      consistency of normalization by local and femoral neck-equivalent T-scores.
      NHANES (femur) and Hologic (spine and forearm) references were applied to
      baseline, 1-, 2-, 3-, and 5-yr scans in 925 untreated women in a national cohort
      study, and alternative local and neck-equivalent scores calculated. The baseline
      prevalence of osteopenia/osteoporosis was 35.5%/4.1% (spine), 31.0%/1.2% (neck),
      31.3%/1.2% (total hip), and 37.2%/2.5% (forearm). It increased to 54.6%/7% by
      combining sites. The prevalences at 5-yr were 57.2%/12.4% (spine), 51.9%/5.0%
      (neck), 46.6%/3.7% (total hip), 52.5%/7.4% (forearm), and 77.3%/17.8% (any). A T
      score cut-off at the lowest of four sites of -1.65 for osteopenia and -3.37 for
      osteoporosis was equivalent in patient numbers to T<-1 and T<-2.5 at the femoral
      neck. The proportion of inconsistently classified subjects decreased from 48% to
      42% (p<0.05) with neck-equivalent scores. No improvement remained after 5 yr.
      Kappa scores did not improve by the use of local or femoral neck scores. In
      conclusion, adjusted thresholds cannot remove the anatomic discrepancy between T
      scores. To overcome this problem, risk-based diagnostic cut-offs must therefore
      be calculated separately for each measurement site and fracture localization.

PMID- 12794231
TI  - Need for precision studies at individual institutions and assessment of size of
      regions of interest on serial DXA scans.
AB  - Precision error is an important quality-control issue in bone densitometry. A
      prospective trial was completed to evaluate whether significance of change on
      serial scans, calculated using least significant change data and 95% confidence
      intervals, from a short-time precision error study, agreed with significance of
      change data determined by internal Hologic scanner software. In addition, the
      constancy of specific bone areas scanned of regions of interest on serial scans
      was evaluated. There was perfect agreement regarding significance of change on
      serial scans in the femoral neck between the Hologic software and internal
      precision data. There was not perfect agreement in the total spine; however, the
      difference was not statistically significant. There was a significant
      disagreement in the total hip and trochanter between the manufacturer's software
      and the precision study. The mean change in the area of the region of interest on
      serial scans was < or =5% in the total spine, total hip, and femoral neck. The
      mean difference in the trochanter was 7.4+/-6.3%. The importance of doing an
      internal precision error study is underscored because significance of change from
      an internal precision study may not agree with manufacturer software. The
      trochanter may be less useful in monitoring serial changes if area of the region
      of interest varies widely.

PMID- 12794233
TI  - A multi-exponential model of postmenopausal decline in vertebral bone mineral
      density: a new approach to the BMD reference range.
AB  - Although the postmenopausal decline in female bone mineral density (BMD) at the
      lumbar spine is central to the World Health Organization (WHO) diagnosis of
      osteoporosis, it has eluded an exact mathematical description. We present a
      simple mathematical model based on the assumption that bone loss can be described
      as an exponential decay process that begins at menopause. Women whose menopause
      begins in the same year of age are assigned a unique exponential function, and
      results from all women are combined to predict the average cross-sectional BMD on
      a year-by-year basis. This model has been successfully validated using data from
      a cross-sectional study of 8,789 female volunteers. No additional "aging" term is
      required. The normal time-constant was estimated to be 5.8 yr, but natural
      variation can have a substantial asymmetric effect on the curve. Similarly,
      variation in the distribution of the age at menopause also has a profound
      influence and can introduce artifacts when different populations of women are
      being compared. Using published data from Finland, it was confirmed that a
      simulation approach can predict the BMD decline observed in typical cross
      sectional studies, suggesting the possibility of a cheaper and more convenient
      way to establish local dual-energy X-ray absorptiometry (DXA) reference curves.

PMID- 12794232
TI  - Normative values of bone parameters of children and adolescents using digital
      computer-assisted radiogrammetry (DXR).
AB  - PURPOSE: To verify whether estimation of bone mineral density (BMD) using digital
      X-ray radiogrammetry (DXR) is possible on children and to determine normative
      values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR
      MCI) on. PATIENTS AND METHODS: In retrospect, X-rays were selected of the hands
      of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The
      involved children were selected among a larger group of children submitted to the
      surgical department of our institute for evaluation of a suspected fracture after
      an occurred trauma. All children with a verified fracture or a chronic bone
      related disease, including bone age retardation or acceleration, were excluded
      from the study. Furthermore, only conventional X-rays with the same film and
      capture parameters were included. The images were scanned and analyzed using the
      Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a
      porosity index (DXR-PI) were automatically calculated using the midshafts of the
      metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately
      for girls and boys in 2-yr intervals. RESULTS: In the present study the system
      has been demonstrated to be capable of calculating DXR-BMD from conventional X
      rays of the hand from children down to approx 6 yr of age. This ability depended
      somewhat on the diameter and the length of the involved metacarpals. The success
      rate was higher for large bones than for small bones. The system succeeded in
      analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to
      increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39
      g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD
      than did boys, corresponding to the earlier entry to puberty of girls. Standard
      deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age
      from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of
      0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and
      girls, respectively. The corresponding correlations for DXR-MCI was lower, with
      observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with
      p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age
      (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the
      calculated mean values. CONCLUSION: The newly available DXR-methodology seems to
      offer the ability to determine DXR-BMD and DXR-MCI in children starting with a
      bone age of 6. This possibility may be of special relevance for children
      suffering from chronic bone diseases that require repeated X-rays of the hand
      (e.g. to determine bone age). The acquired normative data suggest that the
      measurements are of clinical value owing to low age-dependent variability (SDs)
      relative to an observed high increase with age. The clinical value of the
      porosity index (DXR-PI) remains uncertain and is limited owing to a high inter
      individual variability.

PMID- 12794234
TI  - Trabecular and integral bone density in adults with sickle cell disease.
AB  - Sickle cell disease (SCD) is a hereditary disorder of hemoglobin synthesis that
      can affect the skeletal system owing to accelerated hematopoiesis and/or bone
      infarction. Additionally, several studies have suggested that a low bone mass is
      associated with SCD, partly because of adverse effects on growth and development.
      The few previous studies of bone mineral density (BMD) in these patients have
      utilized dual-photon or dual-energy x-ray absorptiometric (DXA) techniques, which
      may have limited value in this population because it cannot correct for
      differences in bone size. We undertook a study of BMD in the forearm of patients
      with sickle cell disease using peripheral quantitative computed tomography (QCT),
      which provides a measure of volumetric bone density for the trabecular bone
      component as well as cortical and trabecular bone together. We studied 32 African
      American SCD patients with no known history of bone infarction in the wrist, and
      compared them with data from healthy African-American volunteers. We found a 13%
      lower integral (cortical and trabecular) BMD in the SCD patients (p=0.001), but
      no difference in trabecular BMD (p=0.40 for males, 0.32 for females). We
      hypothesize that the maintenance of trabecular BMD in the wrist may be related to
      the persistence of metabolically active red marrow in this region in adults with
      SCD.

PMID- 12794235
TI  - Community-based survey of low quantitative ultrasound values of calcaneus in
      Taiwan.
AB  - This study investigated prevalence and associated-factors of low quantitative
      ultrasound (QUS) values by screening calcaneal QUS parameters--broadband
      ultrasound attenuation (BUA) and speed of sound (SOS)--in population samples of
      three different Taiwanese communities. The study included 6,322 subjects (2,631
      male and 3,691 female), aged 31 yr old or more in Shih-Pai (a metropolitan area
      in northern Taiwan),Yu-Chi (a mountain area in central Taiwan), and A-Lein (a
      seaside area in southern Taiwan). The overall response rate was 50.2%. The
      correlation between BUA and SOS was 0.684, p<0.001. From those who responded, we
      selected 403 subjects aged 31-40 yr as the reference (the young group), and their
      BUA was 65.34+/-7.91 dB/MHz. The t-score was calculated from the BUA data of our
      reference group. The percentile of -2.5<t-score<-1.0 and t-score< or =-2.5 in
      male subjects was 21.4 and 2.9%, respectively, and in female subjects 24.2 and
      14.1%, respectively. The BUA of urban area subjects was higher than that of rural
      area subjects in almost all age-strata, and overweight was noted to be a
      protective factor. The effect of age-adjusted odds ratio (AOR) on low QUS values
      in females was significantly increased every 10 yr from 1.55, 5.13, 13.81, 34.29,
      to 38.14. This survey showed that age-related decreases in calcaneal
      ultrasonometry, indicating prevalence of low QUS values, were more obvious in
      female than male subjects. Overall 38.3% of the female Taiwanese had low QUS
      values, and this is approximately equivalent to the lifetime risk of fracture at
      the hip, spine, or distal forearm in Caucasian women. The specific t-score
      designation, as World Health Organization (WHO) criteria, applied to calcaneal
      QUS are reasonable when the reference group is selected from the same population.

PMID- 12794237
TI  - Bone mineral content and soft-tissue assessment in limb segments by dual-energy X
      ray absorptiometry: optimal scan speed and pixel size.
AB  - The aim of this study was to define the best scanning parameters to assess bone
      mineral content (BMC) and bone mineral density (BMD) in specific dual-energy X
      ray absorptiometry (DXA) applications, such as those encountered in orthopedics
      for the measurements of the peripheral skeleton. To simulate soft tissues and
      bones in a limb, we used simple phantoms made with plastic bottles (500 mL and
      1500 mL) filled with tap water and cylinders of hydroxyapatite (HAP) powder set
      in a polymer at various concentrations (range, 0.150-1.500 g HAP/cm3). Data
      obtained from 204 measurements of these phantoms with different scanning speeds
      and pixel sizes showed that the best compromise for obtaining precise
      measurements in the shortest scan time was a scanning speed of 50 mm/s and a
      pixel size of 1.5 mm x 1.5 mm.

PMID- 12794236
TI  - Prevalence of low bone density in institutionalized men with developmental
      disabilities.
AB  - This study investigates the prevalence and degree of low bone mineral density
      (BMD) in a group of 108 institutionalized men with developmental disabilities.
      Speed of sound (SOS) and broadband attenuation (BUA) of the calcaneus were
      measured to determine a quantitative ultrasound index (QUI). Comparison was made
      to the values for this index in a reference population of age-matched and young
      adult controls. Thirty-four percent of the study participants had QUI values more
      than 2 standard deviations (SDs) below those of age-matched controls. Fifty-one
      percent of this population showed QUI values more than 2 SDs below those of the
      young adult reference group, suggesting a high prevalence of significantly
      decreased BMD.

PMID- 12794238
TI  - Precision of single vs bilateral hip bone mineral density scans.
AB  - This study was performed to determine and compare the precision of single and
      bilateral hip bone mineral density (BMD) measurements and to determine the
      precision of spinal and total body measurements by dual-energy X-ray
      absorptiometry (DXA). Precision (group root-mean-square average coefficient of
      variation) was determined in 6 subjects scanned six times each at the spine, both
      hips, and total body, with repositioning after each scan. Mean percentage
      coefficients of variance (%CVs) in BMD for single and bilateral hip scans were,
      respectively: 0.65% and 0.67% for the total hip, 1.16% and 1.03% for the
      trochanter, and 1.66% and 1.31% for the femoral neck, respectively. Mean %CV was
      1.04% for spine BMD (L2-L4), 0.67% for total body BMD, 1.12% for total body bone
      mineral content (BMC), 0.94% for total body fat tissue, and 0.77% for total body
      nonfat soft tissue. We conclude that precision overall is excellent and that
      femoral neck precision can be improved with bilateral compared with the
      traditional single hip scans.

PMID- 12794239
TI  - Hip fracture discrimination study: QUS of the radius and the calcaneum.
AB  - As an emerging alternative to current radiation-based bone densitometry
      techniques, there is a growing interest in the use of quantitative ultrasound
      (QUS) measurements for the noninvasive assessment of fracture risk in the
      management of osteoporosis. However, there are also a multiplicity of
      technologically different QUS devices available on the market and, so far, no
      study has compared heel and radius QUS device for the discrimination of subjects
      with hip fractures. Our study evaluated the ability of three QUS devices (one
      calcaneal gel-coupled system, one calcaneal water-coupled system, and one radius
      system) to discriminate osteoporotic from controls subjects, using the same
      population. We also checked if the combination of two different skeletal sites
      (i.e., calcaneum and radius) improve the discriminatory ability of the QUS
      devices. Forty-five women aged 79.1+/-7.1 yr with hip fractures within the last 4
      d were used as the hip-fracture group and compared to 40 healthy controls from 65
      87 yr. In addition, 47 young controls, aged 20-40 yr, were used as reference
      population to express some of the results as T-scores. QUS measurements were
      performed with the Hologic Sahara, Ge-Lunar Achilles+, and Sunlight Omnisense
      devices according to the manufacturer's recommendations. Adjusted odds ratio
      results showed that a decrease in Omnisense SOS of 1 standard deviation (SD) was
      associated with a significant increase in fracture risk (OR adj.=2.83) comparable
      with Sahara BUA (OR adj.=2.42) and Achilles BUA (OR adj.=3.29). However, given
      the large overlap between the 95% intervals of each odds ratio, no significant
      difference was found between the devices. Similarly, comparison between the areas
      under ROC curves did not show any significant difference between all the
      parameters. Considering the parameters provided per default by each QUS device,
      the Sahara, Achilles, and Omnisense devices classified correctly 70, 67.5, and
      62.5% of the subjects, respectively. Although the OR of the combination of radius
      and calcaneum is improved (3.62 to 4.74) compared with either one of the single
      skeletal site, the large confidence intervals do not allow to claim a significant
      difference. The three QUS technologies tested against hip fractures seem to show
      the same discriminatory ability. However, there is some differences in the
      definition of the diagnostic threshold underlying the nonusability of the World
      Health Organization (WHO) osteoporosis definition. Finally the combination of
      several site using two different devices is not clinically relevant. Potential
      interest could be seen in combining several sites using the same device,
      supposing that such device would measure differently active bone.

PMID- 12794240
TI  - The volumetric bone density and cortical thickness in adult patients affected by
      osteogenesis imperfecta.
AB  - In patients with osteogenesis imperfecta (OI), a disease characterized by
      abnormal bone fragility, bone mineral density (BMD) was found to be relatively
      preserved. Quantitative computed tomography (QCT) is the only available method
      for directly measuring in vivo both volumetric density and the cross-sectional
      area. Here we report the data from dual-energy X-ray absorptiometry DXA (spine
      and hip) and peripheral (pQCT) (ultradistal and proximal radius) measurement of
      27 adult patients affected by OI, mostly of type I, compared with a group of
      healthy persons. In the patients with OI, areal BMD values at both femoral neck
      and lumbar spine were considerably lower than in control subjects (-32 and -36%,
      respectively; p<0.001 for body weight and height adjusted values). pQCT
      volumetric density at the ultradistal radius was 19% lower than in control
      subjects and this difference rose to 32% for purely cancellous bone tissue. The
      whole bone cross-sectional area of ultradistal radius, as measured by pQCT, was
      superimposable to normal. At the proximal radius, both cross-sectional area and
      cortical area, together with Bending Breaking Resistance Index (BBRI), were
      significantly lower in OI (-23; -22; -32% respectively; p<0.001 for body weight
      and height adjusted values), but cortical volumetric density was even slightly
      higher in the OI group than in control subjects. In conclusion, it appears that
      the most obvious defect in adults with OI is the inability to acquire an adequate
      thickness of the cortices of long bone and to achieve or maintain normal
      trabecular density.

PMID- 12794242
TI  - Activation of conventional PKC isoforms increases expression of the pro-apoptotic
      protein Bad and TRAIL receptors.
AB  - BACKGROUND: Pancreatic cancer is a leading cause of cancer death worldwide;
      current treatment options have been ineffective in prolonging survival. Agents
      that target specific signaling pathways (e.g., protein kinase C [PKC]) may
      regulate apoptotic gene expression rendering resistant cancers sensitive to the
      effects of other chemotherapeutic drugs. The purpose of our study was to assess
      the effect of PKC stimulation on apoptotic gene expression in pancreatic cancer
      cells. METHODS: The human pancreatic cancer cell line, PANC-1, was treated with
      PKC-stimulating agents, phorbol 12-myristate 13-acetate (PMA) or bryostatin-1,
      and analyzed for expression of apoptosis-related genes. RESULTS: Both PMA and
      bryostatin-1 induced expression of the pro-apoptotic gene Bad in a dose dependent
      fashion. The expression of Bad was blocked by the PKC inhibitors GF109203x,
      Go6983, and Ro-31-8220, suggesting a role for the conventional isoforms of PKC.
      In addition, treatment with the MEK inhibitors PD98059 or UO126 reduced PMA
      mediated induction of Bad gene expression. PMA also increased the expression of
      TRAIL receptors DR4 and DR5; this expression was inhibited by the PKC inhibitors
      GF109203x, Go6983, and Ro-31-8220 and the MEK inhibitor UO126, suggesting a role
      for conventional PKC isoforms and MEK in the regulation of TRAIL receptor
      expression. CONCLUSIONS: PKC stimulation in PANC-1 cells increases expression of
      the pro-apoptotic gene Bad and the TRAIL receptors, DR4 and DR5, through both
      conventional PKC- and MEK-dependent pathways. Agents that stimulate PKC may
      sensitize pancreatic cancer cells to apoptosis and provide a potential adjuvant
      therapy for the treatment of chemoresistant pancreatic cancers.

PMID- 12794243
TI  - Histopathological study of intraductal papillary mucinous tumor of the pancreas:
      special reference to the roles of Survivin and p53 in tumorigenesis of IPMT.
AB  - AIM: In this study, we investigated the tissue expression of Survivin, p53, and
      Bcl-2 in intraductal papillary-mucinous tumor (IPMT) of the pancreas to identify
      their roles in tumorigenesis of IPMT, and examined their correlations with tumor
      cell apoptosis and proliferation in IPMT. The diagnostic values of the expression
      of Survivin, p53, and Bcl-2 and the apoptotic index (AI) and Ki-67 labeling index
      (Ki-67 LI) in IPMT were also examined. METHODS: Twenty-two lesions from 17
      patients with IPMT, including 12 benign (IPMT Adenoma) and 10 malignant (IPMT
      Carcinoma In Situ [CIS] (n = 4) and Invasive IPMT (n = 6) lesions, were
      immunostained for Survivin, p53, Bcl-2 and Ki-67. The apoptotic cells were
      detected by the Apop Tag(R) In Situ Oligo Ligation (ISOL) method. RESULTS: The
      immunoreactivities for Survivin and p53 significantly increased in the transition
      from IPMT Adenoma to IPMT CIS (p < 0.05 for both). This transition was associated
      with a significant decrease in tumor cell apoptosis ( p < 0.001). The expression
      of Survivin was significantly associated with AI in IPMT ( p < 0.01), but not
      with Ki-67 LI. The expressions of Survivin and p53, and AI and Ki-67 LI were also
      significantly different between benign IPMT and malignant IPMT. Bcl-2 was not
      expressed in IPMT. CONCLUSION: These results suggest that Survivin and p53 may
      play important roles in the transition from IPMT Adenoma to IPMT CIS. This
      transition is accompanied by a significant decrease in tumor cell apoptosis.
      Survivin is significantly associated with the change in AI in IPMT. The
      immunohistochemical detection of Survivin and p53 as well as the determination of
      the AI and Ki-67 LI have useful roles in the diagnosis of IPMT.

PMID- 12794244
TI  - Immunohistochemical expression of TGF-beta1, p21WAF1, p53, Ki67, and angiogenesis
      in gastric carcinomas: a clinicopathologic study.
AB  - BACKGROUND: Transforming growth factors-beta (TGF-betas) are multifunctional
      polypeptides with crucial role as regulators of cellular growth and
      differentiation. It has been reported that TGF-beta1 plays a biphasic action on
      tumorigenesis thus inducing or inhibiting malignant properties of the epithelial
      cells. METHODS: TGF-beta1 expression was analyzed in 56 patients with gastric
      carcinoma by immunohistochemical methods and compared with the expression of p21,
      p53, and Ki67, as well as with angiogenesis. The correlation of these markers
      with clinicopathological parameters was also evaluated. RESULTS: TGF-beta1
      expression was detected in 71% of tumors and was more frequent in adenocarcinomas
      of the intestinal type (p < 0.001). Positivity of p21WAF1, and p53 was observed
      in 32% and 51% of the tumors, respectively. A high Ki67 proliferating index was
      detected in 53.5% of the tumors. TGF-beta1 expression was significantly
      correlated with p21 expression (p < 0.001) and was inversely correlated with
      microvessel density. p21 expression was also higher in tumors with low
      proliferating index (p < 0.01). There was no apparent correlation between the
      expression of these markers and tumor stage, depth of invasion, or lymphnode
      metastases. CONCLUSION: The findings show that TGF-beta1 may be involved in the
      activation of the cdk inhibitor p21WAF1 in gastric adenocarcinomas, suggesting
      p53-independent induction of p21 in gastric cells. TGF-beta1 does not seem to
      contribute to the alteration of the angiogenic status of these tumors.

PMID- 12794246
TI  - CPT-11 for bile-duct and gallbladder carcinoma: a phase II North Central Cancer
      Treatment Group (NCCTG) study.
AB  - BACKGROUND: Bile-duct and gallbladder carcinomas are rare cancers. Once they have
      spread beyond the point of surgical resectability, no therapies have shown
      meaningful long-term benefit. These cancers are typically refractory to standard
      chemotherapy agents. Based on preclinical work showing activity of CPT-11, we
      performed a phase II trial to assess its activity in patients with bile-duct or
      gallbladder carcinomas. METHODS: Patients with histologic or cytologic evidence
      of locally advanced or metastatic bile-duct or gallbladder carcinoma were
      potentially eligible for this study. Patients meeting study eligibility and who
      signed an informed consent were given CPT-11 125 mg/m2 weekly for 4 wk followed
      by a 2-wk break from therapy. The starting dose of CPT-11 was later reduced to
      100 mg/m2 grade IV toxicity. Patients continued on treatment if they showed
      evidence of benefit and tolerated therapy. RESULTS: A total of 39 patients were
      enrolled, and 36 were evaluable. The overall confirmed response rate was 8%. One
      CR and two PRs were seen. A high frequency of toxicity was seen. However, no
      unusual or unexpected toxicities occurred. CONCLUSION: CPT-11 is ineffective
      therapy for patients with locally advanced or metastatic bile-duct or gallbladder
      carcinoma.

PMID- 12794245
TI  - Drug development in pancreatic cancer: finally, biology begets therapy.
AB  - Pancreatic cancer is rarely curable, and only 5% of patients achieve long-term
      survival. The vast majority of patients present with metastatic or unresectable
      disease. Standard chemotherapy with gemcitabine provides clinical benefit to only
      a small minority of patients. Thus, the development and investigation of new
      therapies is clearly needed. As knowledge of the underlying biology of pancreatic
      cancer has increased, targeted therapies based upon preclinical laboratory work
      have been developed, and are entering clinical trials. Some of these agents lack
      traditional dose-limiting toxicities (DLTs) at biologically active doses, and
      therefore clinical evaluation may not follow traditional guidelines for cytotoxic
      drug development. This article focuses on targeted therapies currently undergoing
      clinical evaluation in pancreatic cancer. Classes of therapeutics reviewed
      include those targeting tumor-microenvironment interactions (matrix
      metalloproteinase inhibitors, vascular endothelial growth-factor blockade),
      signal transduction (e.g., farnesyltransferase inhibitors), growth-factor
      receptors (epidermal growth-factor receptor blockade, Her-2/neu, gastrin), and
      vaccine approaches. Currently, there is a renewed optimism that the clinical
      application of biologic understanding will lead to an improved outcome for
      patients with pancreatic cancer.

PMID- 12794247
TI  - A phase II trial of docetaxel and CPT-11 in patients with metastatic
      adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia.
AB  - PURPOSE: The incidence of adenocarcinoma of the lower third of the esophagus,
      esophagogastric junction, and gastric cardia has been rising in the face of
      limited treatment options for patients with metastatic disease. With the
      emergence of data to suggest that single agent docetaxel and irinotecan carry
      antineoplastic effects in this setting, we determined the response rate of these
      agents when given in combination. PATIENTS AND METHODS: Forty-six patients with
      metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric
      junction, and gastric cardia were evaluated. Patients received docetaxel 50
      mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor
      assessment after 2 cycles. Because of unacceptable toxicity among the first 13
      patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d
      intravenously at 21-d intervals. RESULTS: The response rate for the entire cohort
      was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses.
      Five of these 12 responses were observed in patients treated at the higher
      chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia
      and fevers, a dose reduction was incorporated into the protocol, and the
      remainder of the cohort was treated at the lower dose. All except 4 of the 15
      observed grade 4 toxicities occurred at the higher dose, and these toxicities
      included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in
      addition to neutropenia and fevers. There were no grade 5 toxicities. The median
      survival for the entire cohort was 7.3 mo. CONCLUSION: The combination of
      docetaxel and irinotecan provides modest antineoplastic activity among patients
      with adenocarcinoma of the esophagus, esophagogastric junction, and gastric
      cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d
      intervals provide an acceptable safety profile, but higher doses appear to result
      in unacceptable toxicity.

PMID- 12794248
TI  - Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer.
AB  - PURPOSE: This is a phase II study of perillyl alcohol in the treatment of
      patients with metastatic colorectal carcinoma. The primary endpoint is time to
      progression. Secondary objectives are to evaluate objective response rate and
      toxicity. PATIENTS AND METHODS: Eligible patients had metastatic adenocarcinoma
      of the colon or rectum. Patients received perillyl alcohol orally at a dose of
      1200 mg/m2. Dose escalation to 1,600 mg/m2 was allowed. RESULTS: Twenty-seven
      patients were enrolled. The median time to progression was 1.8 months (range 1 to
      3 mo). Four patients received less than one cycle and were not evaluable for
      response. Of the remaining 23, all had progressive disease. There were no
      complete or partial responses. Toxicity was relatively mild, with fatigue, nausea
      and anemia predominating. Three patients withdrew from therapy for toxicity
      (grade 3 belching, bloating; grade 2 nausea, fatigue, vomiting, anorexia and
      increase perspiration; grade 1 anorexia). DISCUSSION: Despite preclinical
      evidence of anticancer activity, oral perillyl alcohol administered at this dose
      and formulation does not appear to have clinical antitumor activity when used for
      patients with advanced colorectal carcinoma.

PMID- 12794249
TI  - Ageism in rectal carcinoma? Treatment and outcome variations.
AB  - BACKGROUND: Rectal cancer adjuvant and neo-adjuvant therapies are associated with
      improved survival and local control rates. Concerns regarding adverse treatment
      effects tend to reduce administration in the elderly-the very population this
      disease affects. PURPOSE: To determine the extent to which age alters rectal
      cancer treatment and its outcome. METHODS AND MATERIALS: Using the population
      based provincial cancer registry, patients with adenocarcinoma of the rectum
      diagnosed between 1991 and 1998 were identified. From this cohort, a random
      subsample of patients seen at the regional cancer center were selected for
      detailed analysis. Demographic and clinical data between the provincial cohort
      and the subsample were compared for homogeneity. Log rank tests and Kaplan-Meier
      survival estimates were carried out on the subsample. RESULTS: The population
      cohort (n = 1979) and the subsample (n = 259) were similar in age, sex, and
      treatment distributions. Elderly patients (>/=75 yr) made up 23% of the rectal
      cancer population in Alberta. Age had a highly significant (p = 0.001) impact on
      whether patients received surgery alone or had surgery plus chemoradiotherapy.
      This corresponded to a considerable survival advantage for those elderly patients
      who did receive multimodality therapy (p = 0.008). CONCLUSION: The advantage of
      multimodality therapy in rectal cancer is confirmed in this populationbased
      study. Although a significant number of elderly patients are fit enough to
      tolerate major surgery they are being denied adjuvant therapies, presumably on
      the basis of potentially high treatment-related complication rates, with a
      subsequent reduction in survival. Strategies must be developed to ensure that
      maximum treatment benefit is obtained without increased harm in the elderly
      rectal cancer patient.

PMID- 12794250
TI  - The pilot experience of immunotherapy-combined photodynamic therapy for advanced
      gastric cancer in elderly patients.
AB  - BACKGROUND: Therapeutic efficacy of endoscopic photodynamic therapy (PDT) for
      advanced gastric cancer is limited. Recent animal studies have clarified the very
      important role of host immune cells in PDT. We expected a potential cooperative
      effect of PDT and immunotherapy, and developed immunotherapycombined PDT (I-PDT)
      for advanced gastric cancer. METHODS AND MATERIALS: We applied I-PDT for two
      elderly patients with complicated advanced gastric cancer (92- and 89-yr-old
      males). Tumor bleeding prevented them from leading an ordinary home life. Initial
      simple PDT was not effective. Patients received over 109 activated T-lymphocyte
      predominant autologous immune cells, mainly intravenously, 5x for one course. PDT
      was performed endoscopically on the day of the third infusion. RESULTS: Two or
      three courses of I-PDT safely stopped tumor bleeding, and the initial poor
      prognoses of a few months of survival seemed to be improved (patient 1, over 32
      mo; patient 2, 14 mo). CONCLUSIONS: I-PDT was found to be a safe, feasible
      treatment that could improve symptoms resulting from advanced gastric cancer.

PMID- 12794252
TI  - Symptomatic pancreatic polypeptide-secreting tumor of the distal pancreas
      (PPoma).
AB  - Our report describes a 46-yr-old woman who presented with watery diarrhea in the
      presence of multiple endocrine neoplasia type I (MEN I) syndrome. Of various
      potential pancreatic endocrine hormones, only serum levels of pancreatic
      polypeptide were elevated. Radiologic imaging failed to identify a pancreatic
      tumor; her diarrhea was therefore managed with subcutaneous administration of
      somatostatin. Three years later she developed gallstone pancreatitis with the
      subsequent development of a pancreatic pseudocyst. At exploration for drainage of
      the pseudocyst, intraoperative ultrasound identified a 6-mm tumor in the distal
      pancreas that was resected. Final pathology documented a pancreatic endocrine
      tumor with immunohistochemical staining demonstrating the presence of pancreatic
      polypeptide. The present case illustrates the symptomatology that may be
      associated with pancreatic polypeptide-secreting endocrine tumors of the
      pancreas.

PMID- 12794251
TI  - Unusually high rate of young-onset pancreatic cancer in the East Nile Delta
      region of Egypt.
AB  - BACKGROUND: Pancreatic cancer is predominantly a disorder of the elderly
      population in the United States. In Egypt, the disease has traditionally been
      considered rare, and there has not been a previous publication on its population
      based incidence or age distribution. METHODS: We reviewed the records of 728
      pancreatic cancer patients seen at the Gastrointestinal Surgery Center of
      Mansoura University in the East Nile Delta region of Egypt between 1995 and 2000.
      We computed population-based, age-specific, and age-adjusted incidence rates in
      this population and compared them with US incidence rates from the Epidemiology
      Surveillance and End Results (SEER) Program. We also analyzed clinical
      characteristics of the patients, as well as their surgical and medical
      management. RESULTS: Approximately one-fourth of all patients were under age 50.
      The mean ages of patients who had undergone Whipple's resection, other surgical
      procedures, and no surgical procedure were 52.9 +/- 11.6, 54.11 +/- 10.5, and
      55.1 +/- 14.1 yr, with no statistically significant differences. Age-adjusted
      incidence rates were higher in Egyptian patients than in US patients under age 65
      (7.1/100,000 vs 3.3/100,000) but were much higher in US patients than in Egyptian
      patients over age 65 (6.6/100,000 vs 59.1/100,000). Clinical management did not
      differ between patients under and over age 50. CONCLUSION: The population in the
      East Nile Delta region of Egypt exhibits an unusually high rate of young-onset
      pancreatic cancer. Further studies to investigate the epidemiology of pancreatic
      cancer in this population may provide clues to its etiology.

PMID- 12794253
TI  - Cecum malakoplakia: a tumor-like lesion with coexistent adenocarcinoma.
AB  - We report the case of a 75-year-old Caucasian male who presented with acute
      abdomen and fecal leakage from his old appendectomy scar and required exploratory
      laparotomy. A large cecal mass was found and a right colectomy was performed. At
      pathology, the neoplastic mass was identified as malakoplakia with a small area
      corresponding to a moderately differentiated colonic adenocarcinoma. Occurrence
      of malakoplakia in the cecum, associated with adenocarcinoma, is extremely rare
      if we take into account the limited number of the reported cases of its
      coexistence with colonic cancer; our case is the second report of such an entity
      in the cecum. The unusual presence of fistula to the appendectomy scar may be
      related to the infiltrative nature of the histiocytes constituting this process.
      Immunochemical studies can assist in the histopathologic differentiation of
      malakoplakia from other entities that might represent with this tumor-like
      configuration.

PMID- 12794254
TI  - EUS changes diagnosis from pancreatic to gallbladder carcinoma.
AB  - A patient was referred for endoscopic ultrasound (EUS) for preoperative staging
      of what was believed to be pancreatic cancer, based on minimal findings on
      computed tomography (CT) and highly elevated CA19-9. EUS imaged a normal
      pancreas, but a tumor mass was identified in the gallbladder, and proven to be
      adenocarcinoma using EUS-guided fine-needle aspiration (FNA). Open
      cholecystectomy was curative. CA19-9 is not a highly specific marker. EUS is
      emerging as a highly sensitive and specific test for pancreatic cancer. EUS can
      complement other imaging modalities, and reveal unsuspected pathologies, such as
      in the patient described in this report, with major clinical impact.

PMID- 12794255
TI  - A case of colonic ischemia mimicking carcinoma.
AB  - In this article, we describe a case of colonic ischemia masquerading as colonic
      carcinoma in a 75-yr-old female. Although this clinical diagnostic problem has
      been described before, it is rather unusual that the clinical,
      roentgenographical, endoscopic, and even histopathologic evaluation could not
      exclude carcinoma with certainty.

PMID- 12794256
TI  - The epidemiology of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is the most diverse of the autoimmune diseases
      because it may affect any organ of the body and display a broad spectrum of
      clinical and immunological manifestations. Although previously considered a rare
      disease, SLE now appears to be relatively common in certain groups of the
      population. This is probably due to the development of several immunological
      tests that have allowed the description of many atypical or benign cases that
      otherwise might not be diagnosed. Furthermore, with the introduction since 1982
      of a set of more sensitive criteria for SLE classification, more cases can
      nowadays be detected. In the present article, we review the most important data
      regarding the incidence and prevalence of this disease in the general population,
      the epidemiologic information on the patterns of disease expression in specific
      subsets and the studies on mortality in SLE. An important amount of information
      comes from the data obtained from the "Euro-Lupus Cohort," a series of 1000
      patients with SLE from several European countries that have been followed
      prospectively since 1991.

PMID- 12794257
TI  - Osteonecrosis in patients with SLE.
AB  - Osteonecrosis is a clinical entity characterized by death of bone marrow and
      trabecular bone as a result of disruption of blood supply to the bone (1,2).
      Other aspects of this condition include avascular necrosis, aseptic necrosis, and
      osseous ischemic necrosis of bones. Osteonecrosis is classified into two main
      forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis
      usually develops as a result of traumatic displacement of bone fragments, which
      leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis
      of the femoral head is common following fracture of the femoral neck. A variety
      of systemic diseases and clinical conditions are associated with nontraumatic
      osteonecrosis. These include autoimmune rheumatic diseases, alcoholism,
      pregnancy, Gaucher's disease, thrombophilia, corticosteroid therapy, Sickle-cell
      anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and
      others. Idiopathic forms of osteonecrosis have also been reported (2-4). Among
      the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus
      erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients
      with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and
      systemic vasculitis (8). This article reviews the causes, clinical and
      epidemiological features, diagnosis, and treatment options for osteonecrosis
      among patients with SLE.

PMID- 12794258
TI  - Fibromyalgia in systemic lupus erythematosus: prevalence and clinical
      implications.
AB  - Fibromyalgia (FM) is common in SLE patients, and is the source of many of the
      symptoms and much of the disability in these patients. The association of FM and
      SLE may pose diagnostic dilemmas. Fibromyalgia does not correlate with SLE
      disease activity, but the clinical features of FM in these patients may
      contribute to a misinterpretation of lupus activity. The recognition of the
      association between SLE and FM is relevant to every physician who treats lupus
      patients.

PMID- 12794259
TI  - SLE and infections.
AB  - Infections are common in systemic lupus erythematosus (SLE), and remain a source
      of mortality. The types of infections (such as pneumonia, urinary tract
      infection, cellulitis, and sepsis) in SLE patients are similar to the general
      population and include the same pathogens (Gram-positive and Gram-negative). SLE
      patients may also develop opportunistic infections, especially when treated with
      immunosuppressive agents. As a high-risk population, identification and treatment
      of chronic infections such as tuberculosis, hepatitis B, or human
      immunodeficiency virus (HIV), are important prior to the institution of
      immunosuppression to prevent reactivation or exacerbation of the infection. A
      common caveat is to distinguish between a lupus flare and an acute infection;
      judicious use of corticosteroids and cytotoxic drugs is critical in limiting
      infectious complications. The risk factors associated with susceptibility to
      disease include severe flares, active renal disease, treatment with moderate or
      high doses of corticosteroids and/or immunosuppressive agents, and others.
      Genetic factors (complement deficiencies, mannose-binding lectin, Fcgamma III,
      granulocyte macrophage colony-stimulating factor [GM-CSF], osteopontin) may
      predispose certain SLE patients to develop infections. Parameters including C
      reactive protein (CRP) and adhesion molecules may help to differentiate an
      infectious disease from an exacerbation of the disease. Finally, the mechanism of
      molecular mimicry by specific microbial agents may play a role in the induction
      of SLE.

PMID- 12794260
TI  - Systemic lupus erythematosus and parvovirus B-19: casual coincidence or causative
      culprit?
AB  - Systemic lupus erythmatosus (SLE) is a multi-system autoimmune disease
      characterized by auto-reactive cells and auto-antibodies, which can potentially
      affect all organ systems. Typical organ systems that are affected include the
      heart, lungs, skin, kidneys, and central nervous system. Its expression is
      believed to be dependent on various factors such as genetic predisposition,
      environmental agents, immune dysregulation, crossreactivity with auto-antigens,
      alterations in auto-antigens, or most likely, a combination of these. Parvovirus
      B19, a virus which commonly runs an asymptomatic or benign self-limiting course
      such as erythema infectiosum, transient aplastic crisis, flu-like symptoms, rash,
      arthalgia, and arthritis, has recently been associated with a number of rheumatic
      diseases, more specifically with SLE. Like SLE, it can present with multi-
      systemic symptoms resembling SLE both clinically and serologically. Similarities
      have been so striking that patients have been initially misdiagnosed with SLE,
      having fulfilled 3-5 of the criteria of the American College of Rheumatology,
      currently used for the diagnosis of SLE, only to discover later that they were
      infected by parvovirus B19. This paper will discuss parvovirus' link to SLE, its
      similarities and differences, and whether parvovirus can act as a trigger of, or
      simply mimic, SLE.

PMID- 12794261
TI  - Systemic lupus erythematosus and apoptosis: a question of balance.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized
      by the presence of autoantibodies directed against a range of intracellular
      nucleoprotein targets. SLE patients are believed to develop an autoimmune
      response triggered by surface-exposed intracellular macromolecules translocated
      to the cell surface during apoptosis. Apoptosis-or programmed cell death-is a
      genetically controlled process initiated by two principal pathways. The extrinsic
      pathway is activated by the ligation of death receptors, and the intrinsic
      pathway emerges from mitochondria. As shown in fas-deficient mice and humans, the
      inability of the immune system to eliminate self-reactive lymphocytes by
      apoptosis can cause persistence of autoreactive cells and autoimmunity. However,
      as shown in complement deficiencies, increased apoptotic material and altered
      clearance of apoptotic cells is found in patients with SLE. These results suggest
      that what is found in rare individuals with genetic deficiencies that develop SLE
      or SLE-like disease may be found in the larger population of SLE patients as a
      common end point pattern of unbalanced process of both apoptosis and clearance of
      apoptotic material.

PMID- 12794263
TI  - Atherosclerosis and antiphospholipid syndrome.
AB  - Atherosclerosis is an autoimmune/inflammatory disease associated with infectious,
      inflammatory, and autoimmune factors. Both humoral and cellular immune mechanisms
      have been proposed to participate in the onset and/or progression of atheromatous
      lesions. Heat-shock protein (hsp), oxidized low-density lipoprotein (LDL), and
      beta2-GPI have been reported to elicit humoral and cellular immune response in
      both experimental animals and humans. These autoantigens are expressed within
      atherosclerotic lesions. Immunization with the given autoantigens elicits an
      immune response that influences lesion progression. Atherosclerosis
      susceptibility can be transferred by autoantigen-sensitized lymphocytes from
      immunized animals. Patients with systemic lupus erythematosus (SLE) and
      antiphospholipid syndrome (APS) have a high risk for atherosclerotic
      cardiovascular events. The traditional risk factors fail to fully account for
      accelerated atherosclerosis in SLE and APS. Immunological alterations, such as
      antibodies to oxidized LDL, antiphospholipid antibodies (aPL), antibodies to beta
      2 Glycoprotein (anti-beta2-GPL), anti-prothrombin antibodies, may play a role in
      premature atherosclerosis in SLE and APS. Paraoxonase (PON1) is an enzyme with
      antioxidant activity attached to the circulating high-density lipoprotein (HDL)
      in plasma. Its function is to prevent oxidation of LDL, thereby accounting for
      the antioxidant properties and the atherosclerotic protective effects of HDL. The
      relationship between PON1 and aPL has been recently suggested. IgG anti-HDL and
      IgG anti-beta2-GPI antibodies were associated with reduced PON1 activity in
      patients with SLE and primary APS. The determination of classic and new factors,
      together with specific autoantibody titers and the use of Doppler carotid
      ultrasound, are useful methods to detect early atherosclerosis in SLE and PAPS.
      Therapeutic strategies, including early control of disease and other risk
      factors, are essential to reduce morbidity and mortality.

PMID- 12794262
TI  - Unusual manifestations of the antiphospholipid syndrome.
AB  - The classical clinical picture of the antiphospholipid syndrome (APS) is
      characterized by venous and arterial thromboses, fetal losses and
      thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely
      lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or antibodies to the
      protein "cofactor" b2 glycoprotein I. Single vessel involvement or multiple
      vascular occlusions may give rise to a wide variety of presentations. Any
      combination of vascular occlusive events may occur in the same individual and the
      time interval between them also varies considerably from weeks to months or even
      years. Deep vein thrombosis, sometimes accompanied by pulmonary embolism, is the
      most frequently reported manifestation in this syndrome. Cerebrovascular
      accidents-either stroke or transient ischemic attacks-are the most common
      arterial thrombotic manifestations. Early and late fetal losses, premature births
      and pre-eclampsia are the most frequent fetal and obstetric manifestations.
      Additionally, several other clinical features are relatively common in these
      patients, i.e., thrombocytopenia, livedo reticularis, heart valve lesions,
      hemolytic anemia, epilepsy, myocardial infarction, leg ulcers, and amaurosis
      fugax. However, a large variety of other clinical manifestations have been less
      frequently described in patients with the APS, with prevalences lower than 5%.
      These include, among others, large peripheral or aortic artery occlusions,
      Sneddon's syndrome, chorea, transverse myelopathy, intracardiac thrombus, adult
      respiratory distress syndrome, renal thrombotic microangiopathy, Addison's
      syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia of the liver,
      avascular necrosis of the bone, cutaneous necrosis or subungual splinter
      hemorrhages. In this article, some of these "unusual" manifestations are
      reviewed.

PMID- 12794265
TI  - Novel Approaches to Therapy for SLE.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multi
      organ involvement and elevated titers of anti-DNA antibodies. Current therapies
      for SLE are broadspectrum, and include steroids and immunosuppressive cytotoxic
      agents that are counterbalanced by the toxicity and side effects of the
      medications. One of the goals is to target therapies by altering specific known
      mechanisms of inflammation and autoimmunity. Although the inciting antigen is
      still unknown in SLE, it may be possible to alter the regulation of the immune
      response by targeted molecular therapy. Methods under investigation, which may be
      beneficial, are manipulation of second-signal stimulation of the immune response
      (anti-CD40L), manipulation of cytokines (monoclonal anti-IL-10), inducing
      tolerance by administration of blocking peptides (LJP394), and the manipulation
      of idiotypes (IVIg). In this article, we also discuss modalities that are steroid
      sparing (MTX), and selective immunosuppression (stem-cell restoration and MMF).
      We review the ongoing literature from 2000-2002, utilizing the MEDLINE search.
      Controlled trials, open trials, and trials in phase I and II have been included,
      and anecdotal reports were excluded. The major advances have been with
      mycophenolate mofetil (MMF) and LJP 394.

PMID- 12794264
TI  - Immunopathogenesis of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterized by the sicca
      symptoms of dry eyes and dry mouth. Glandular dysfunction is thought to arise
      from destruction associated with lymphocytic infiltration. The degree of
      glandular destruction, however, does not correlate with the severity of sicca
      symptoms, suggesting that other mechanisms are involved, including abnormalities
      in parasympathetic neurotransmission. Autoantibodies against the muscarinic
      acetylcholine receptor have been implicated in this process, but multiple other
      autoantibodies have been found. Cytokines elaborated in the inflammatory lesions
      also appear to be involved and dysregulation of apoptosis are also involved in
      the pathogenesis of SS. A new two-stage model of SS has been proposed. First,
      there is a lymphocyte-independent phase during which inappropriate apoptosis
      results in the generation of apoptotic autoantigens which then attract
      lymphocytes. Subsequently, in the second lymphocyte-dependent phase, an immune
      attack causes further cell death and salivary dysfunction. Although the disease
      generally takes a rather stable and benign course, patients with SS have a
      significant risk of developing B cell lymphoma.

PMID- 12794267
TI  - Sample preparation and imaging of erythrocyte cytoskeleton with the atomic force
      microscopy.
AB  - A novel method for the covalent attachment of erythrocytes to glass microscope
      coverslips that can be used to image intact cells and the cytoplasmic side of the
      cell membrane with either solid or liquid mode atomic force microscopy (AFM) is
      described. The strong binding of cells to the glass surface is achieved by the
      interaction of cell membrane carbohydrates to lectin, which is bound to N-5-azido
      2-nitrobenzoyloxysuccinimide (ANBNOS)-coated coverslips (1). The effectiveness of
      this method is compared with the other commonly used methods of immobilizing
      intact erythrocytes on glass coverslips for AFM observations. Experimental
      conditions of AFM imaging of biologic tissue are discussed, and typical
      topographies of the extracellular and the cytoplasmic surfaces of the plasma
      membrane in the dry state and in the liquid state are presented. Comparison of
      the spectrin network of cell age-separated erythrocytes has demonstrated
      significant loss in the network order in older erythrocytes. The changes are
      quantitatively described using the pixel height histogram and window size grain
      analysis.

PMID- 12794266
TI  - Hyperoxia augments pulmonary lipofibroblast-to-myofibroblast
      transdifferentiation.
AB  - Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality
      in premature infants, and despite many advances, its pathophysiology remains
      incompletely understood. Exposure of the premature lung to hyperoxia is commonly
      implicated in its pathogenesis. However, the exact link between hyperoxia and
      BPD, particularly its role in the generation of myofibroblasts, the signature
      cell-type for lung fibrosis, is undetermined. There is increasing evidence that
      lipid interstitial fibroblasts play an important role in injury-repair mechanisms
      in various organ systems. This study demonstrates that exposure to hyperoxia
      augments the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts.
      Fetal rat lung fibroblasts (FRLF) from embryonic (e) (term = e22) 18 and e21
      gestation were studied. After initial culture in minimum essential medium (MEM)
      and 10% fetal bovine serum (FBS) in 21% O2 / 5% CO2 at 37 degrees C, FRLF were
      maintained in MEM and 10%FBS at 37 degrees C under control (21% O2 / 5% CO2) and
      under experimental conditions (24-hour exposure to 95% O2 /5% CO2) at passage (P)
      1 and 5. At each passage, cells were allowed to attach to 100 cm2 culture dishes
      and grow in 21% O2 before being subjected to the experimental conditions. Passage
      1 and 5 cells were analyzed for the expression of well-characterized lipogenic
      and myogenic markers based on semiquantitative competitive RT-PCR (for
      parathyroid hormone-related protein receptor [PTHrPR]), adipose differentiation
      related protein (ADRP), and alpha smooth muscle actin (alphaSMA), triglyceride
      uptake, and leptin assay. Serial passage and maintenance of cells in 21% O2
      resulted in a significant decrease in the expression of the lipogenic markers
      from P1 to P5, spontaneously. This decrease was greater for e18 than for e21
      FRLF. However, exposing cells to 95% O2 augmented the loss of the lipogenic
      markers and gain of the myogenic marker from P1 to P5 in comparison to cells
      maintained in 21% O2. These changes were also greater for e18 vs e21
      lipofibroblasts. These changes in mRNA expression were accompanied by decreased
      triglyceride uptake and leptin secretion on exposure to hyperoxia. These results
      suggest that exposure to hyperoxia (95% O2) augments the transdifferentiation of
      pulmonary lipofibroblasts to myofibroblasts.

PMID- 12794268
TI  - Model building and model checking for biochemical processes.
AB  - A central claim of computational systems biology is that, by drawing on
      mathematical approaches developed in the context of dynamic systems, kinetic
      analysis, computational theory and logic, it is possible to create powerful
      simulation, analysis, and reasoning tools for working biologists to decipher
      existing data, devise new experiments, and ultimately to understand functional
      properties of genomes, proteomes, cells, organs, and organisms. In this article,
      a novel computational tool is described that achieves many of the goals of this
      new discipline. The novelty of this system involves an automaton-based semantics
      of the temporal evolution of complex biochemical reactions starting from the
      representation given as a set of differential equations. The related tools also
      provide ability to qualitatively reason about the systems using a propositional
      temporal logic that can express an ordered sequence of events succinctly and
      unambiguously. The implementation of mathematical and computational models in the
      Simpathica and XSSYS systems is described briefly. Several example applications
      of these systems to cellular and biochemical processes are presented: the two
      most prominent are Leibler et al.'s repressilator (an artificial synthesized
      oscillatory network), and Curto- Voit-Sorribas-Cascante's purine metabolism
      reaction model.

PMID- 12794269
TI  - The cellular prion protein: biochemistry, topology, and physiologic functions.
AB  - Studies on the transmission from man to animals of Creutzfeld-Jacob disease (CJD)
      led Prusiner to identify a proteinaceous infectious particle lacking nucleic
      acid, which was called prion. The identification of the infectious prion (PrPsc)
      then led to the discovery of the normal cellular counterpart (PrPc). One of the
      still enigmatic aspects regarding prion diseases is actually how, where, and when
      the transformation PrPc/PrPsc is occurring, this being due to the result of a
      large extent to the fact that so far most studies have been dedicated to the
      formation and transmission of PrPsc, whereas the understanding of physiologic
      roles of PrPc are in their infancy. In this review, we hope to identify the most
      reliable hypotheses for future experiments on PrPc. This is relevant not only for
      the understanding of PrPc functions but also to unravel the enigmatic nature of
      PrPc/PrPsc conversion.

PMID- 12794271
TI  - Differential responsiveness of vascular endothelial cells to different types of
      fluid mechanical shear stress.
AB  - Early atherosclerotic lesions localize preferentially in arterial regions exposed
      to low flow, oscillatory flow, or both; however, the cellular basis of this
      observation remains to be determined. Atherogenesis involves dysfunction of the
      vascular endothelium, the cellular monolayer lining the inner surfaces of blood
      vessels. How low flow, oscillatory flow, or both may lead to endothelial
      dysfunction remains unknown. Over the past two decades, fluid mechanical shear
      (or frictional) stress has been shown to intricately regulate the structure and
      function of vascular endothelial cells (ECs). Furthermore, recent data indicate
      that beyond being merely responsive to shear stress, ECs are able to distinguish
      among and respond differently to different types of shear stress. This review
      focuses on EC differential responses to different types of steady and unsteady
      shear stress and discusses the implications of these responses for the
      localization of early atherosclerotic lesions. The mechanisms by which
      endothelial differential responsiveness to different types of flow may occur are
      also discussed.

PMID- 12794270
TI  - Endothelial signaling in leukocyte transmigration.
AB  - Leukocyte transendothelial migration is a multistep process coordinated by
      chemokine receptors, integrins and cell adhesion molecules. The interaction
      between leukocytes and endothelial cells is accompanied by bidirectional
      signaling in both cell types, which is initiated following formation of
      specialized, "docking" structures. In recent years, it has become clear that
      signaling in the endothelial cells importantly contributes to the transmigration
      process. This signaling induces a focal and transient loss of endothelial cell
      cell adhesion, which is dependent on vascular-endothelial cadherin. Recent work
      from several groups has implicated Rho-like GTPases, reactive oxygen species,
      changes in the actin cytoskeleton and protein tyrosine phosphorylation in the
      control of VE-cadherin and associated proteins. This review discusses what is
      currently known about control of VE-cadherin function via intracellular
      signaling, and its induction by endothelial adhesion molecules of the
      immunoglobulin superfamily.

PMID- 12794272
TI  - Current knowledge of iron metabolism.
AB  - Iron plays many roles in human physiology. In this article, we summarize the
      basic and current knowledge of this essential micronutrient on human metabolism.

PMID- 12794273
TI  - Selenium concentrations in human renal cortex, liver, and hair in northern
      Poland.
AB  - The aim of this study was to (1) determine the selenium concentration in the
      renal cortex, liver, and hair in 64 residents from northern Poland (Gdansk
      region) aged 17-81 yr, who died suddenly, and (2) assess whether a correlation
      between the selenium concentration in hair and in the renal cortex and liver
      occurs. Selenium was determined by atomic absorption spectrometry using the
      hydride generation method. The mean selenium concentration in the renal cortex,
      liver, and hair in the investigated persons was 0.791+/-0.191 microg/g (wet
      weight), 0.289+/-0.084 microg/g (wet weight), and 0.443+/-0.128 microg/g,
      respectively. No age-dependent differences in selenium level in the investigated
      tissues was found. Also, no correlation between the selenium concentrations in
      hair and in renal cortex and liver was assessed.

PMID- 12794274
TI  - Effect of aluminum on the blood-brain barrier permeability during nitric oxide
      blockade-induced chronic hypertension in rats.
AB  - We examined the effect of aluminum on the permeability of the blood-brain barrier
      (BBB) during nitric oxide-blockade-induced chronic hypertension in rats. Animals
      were given the inhibitor of nitric oxide synthase, L-NAME (Nomega-nitro-L
      arginine methyl ester), for 4 wk to induce chronic hypertension. Two groups of
      rats were given an intraperitoneal injection of aluminum chloride. The integrity
      of the BBB was assessed by a quantitative measurement for Evans blue (EB) dye.
      The arterial blood pressure in L-NAME- and L-NAME plus aluminum-treated animals
      was significantly elevated from 115+/-2.8 and 110+/-1.7 mm Hg to 174+/-5.2 and
      175+/-4.8 mm Hg, respectively (p < 0.01). The EB dye content in the brain regions
      of the rats in the L-NAME group was increased, but there was no statistical
      significance compared to the saline group. The extravasation of EB dye was
      significantly increased in the brain regions of the animals treated with aluminum
      compared to the rats treated with saline (p < 0.05). A significantly higher EB
      dye content in the brain regions was observed in the L-NAME plus aluminum group
      compared to L-NAME, aluminum, and saline groups (p < 0.01). These findings
      indicate that exposure to a high level of aluminum leads to an additional
      increase in BBB permeability where nitric oxide-blockade-induced chronic
      hypertension potentiates the effect of aluminum to enhance BBB permeability to EB
      dye.

PMID- 12794275
TI  - Accumulation of aluminum in rat brain: does it lead to behavioral and
      electrophysiological changes?
AB  - The present study was undertaken to examine possible aluminum (Al) accumulation
      in the brain of rats and to investigate whether subchronic exposure to the metal
      leads to behavioral and neurophysiological changes in both treated and control
      groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at
      a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by
      gavage for 8 wk. Al-free water by gavage was given to the control group
      throughout the experiment. Behavioral effects were evaluated by open-field (OF)
      motor activity and by acoustic startle response (ASR). Electrophysiological
      examination was done by recording spontaneous activity and sensory-evoked
      potentials from the visual, somatosensory, as well as auditory cortex. The Al
      content of each whole brain was determined by electrothermal atomic absorption
      spectrophotometry. Subchronic Al exposure slightly caused some changes in the
      evoked potentials and electrocorticograms and in the OF and ASR performance, but
      these results were not statistically significant. The brain Al levels of the
      control and the low and high dose of Al-exposed groups were measured as 0.717+/
      0.208 microg/g (wet weight), 0.963+/-0.491 microg/g (wet weight) and 1.816+/
      1.157 microg/g (wet weight), respectively.

PMID- 12794277
TI  - Effect of bioaccumulation of cadmium on biomass productivity, essential trace
      elements, chlorophyll biosynthesis, and macromolecules of wheat seedlings.
AB  - Soil contamination with heavy metals has become a worldwide problem, leading to
      losses in agricultural yield and hazardous human health effects as they enter the
      food chain. The present investigation was undertaken to examine the influence of
      cadmium (Cd2+) on the wheat (Triticum aestivum L.) plant. Cd2+ accumulation and
      distribution in 3-wk-old seedlings grown in nutrient medium containing varying
      concentrations of Cd2+ (control, 0.25, 0.50, 1.0, 2.5, and 5.0 mg/L) was
      monitored. The effect of varying Cd2+ concentrations up to 21 d on biomass
      productivity, plant growth, photosynthetic pigments, protein, amino acids,
      starch, soluble sugars, and essential nutrients uptake was studied in detail to
      explore the level up to which the plant can withstand the stress of heavy metal.
      Plants treated with 0.5, 1.0, 2.5, and 5.0 mg/L Cd2+ showed symptoms of heavy
      metal toxicity as observed by various morphological parameters which were
      recorded with the growth of plants. The root, shoot-leaf length and the root,
      shoot-leaf biomass progressively decreased with increasing Cd2+ concentration in
      the nutrient medium. Cd2+ uptake and accumulation was found to be maximum during
      the initial growth period. Cd2+ also interfered with the nutrients uptake,
      especially calcium (Ca2+), magnesium (Mg2+), potassium (K+), iron (Fe2+), zinc
      (Zn2+), and manganese (Mn2+) from the growth medium. Growth reduction and altered
      levels of major biochemical constituents such as chlorophyll, protein, free amino
      acids, starch, and soluble sugars that play a major role in plant metabolism were
      observed in response to varying concentrations of Cd2+ in the nutrient medium. In
      the present study, the effects of Cd2+ on growth, biomass productivity, mineral
      nutrients, chlorophyll biosynthesis, protein, free amino acid, starch, and
      soluble sugars in wheat plants was estimated to establish an overall picture of
      the Cd2+ toxicity at structural and functional levels.

PMID- 12794276
TI  - Relationship between lead-induced biochemical and behavioral changes with trace
      element concentrations in rat brain.
AB  - Lead has an obvious potential to disturb learning ability, adaptive responses,
      and other aspects of behavior and even personality in those who may appear
      healthy according to conventional medical criteria. These disturbances are shown
      to be associated with alterations in ionic, cholinergic, and dopaminergic
      neurotransmission in the central nervous system (CNS). The present experiment was
      designed to study the neurotoxic consequences of lead exposure on
      neurotransmitters like dopamine, serotonin, norepinephrine, and activity of
      acetylcholinestrase, as well as some ions like zinc, calcium, sodium, and
      potassium. The locomotory functions along with cognitive functions and memory
      loss were also studied at various dose levels. Lead was administrated orally in
      doses of 10 mg/kg, 50 mg/kg, and 200 mg/kg for a period of 12 wk and the study
      was done at the end of exposure. A dose-dependent decrease in the concentration
      of sodium, potassium, and zinc was observed; there was increase in the
      concentrations of lead and calcium. The most significant change noted was the
      decrease in activity of the acetylcholinestrase and other neurotransmitters. Lead
      exposure affected the locomotor and cognitive functions. Short-term memory
      remained unchanged at all lead exposure doses.

PMID- 12794278
TI  - A study of some serum mineral levels before and during pregnancy and during
      lactation period of sheep and cattle.
AB  - The purpose of this study was to determine serum Cu, Zn, Mn, K, and Mg levels
      before and during pregnancy and during the lactation period of sheep and cattle
      and to determine the relationships between periods. For this purpose, blood
      samples of 14 healthy, pregnant Brown Swiss cows fed under normal condition and
      36 Karakas (Ivesi x Akkaraman) sheep were used. Blood samples were analyzed using
      an atomic absorption spectrophotometer. There were significant differences
      between before pregnancy and during pregnancy, and during pregnancy and the
      lactation period for serum Zn concentration; also before pregnancy and during
      pregnancy, and before pregnancy and the lactation period for serum K
      concentration in cows (p<0.05). There were significant differences between before
      pregnancy and the lactation period for serum Cu concentration, and before
      pregnancy and during pregnancy for serum K concentration; also pregnancy and the
      lactation period for serum Mg concentration in sheep (p<0.05).

PMID- 12794279
TI  - Food and Agriculture Organization Symposium: Anaerobic Digestion. May 19-22,
      2002, Moscow, Russia. Proceedings.

PMID- 12794280
TI  - Combining mixing regimes for optimized anaerobic wastewater treatment.
AB  - Operational practice of high-rate anaerobic bioreactors such as upflow anaerobic
      sludge bed (UASB) reactors is generally based on maximization of the biomass
      concentration and, in the case of more than one reactor compartment, operation in
      parallel. In this article, a modeling approach is used to postulate that the
      treatment performance of anaerobic bioreactors can be improved by simple
      operational measures. To achieve minimized effluent soluble substrate
      concentrations, operation of two reactors in series combined with active exchange
      of biomass between both reactors is suggested. In this way, substrate
      concentrations lower than the minimum achievable concentration in a completely
      mixed reactor can be achieved. It is furthermore suggested that maximized biomass
      concentrations (and solid retention times [SRTs]) do not necessarily lead to
      minimized effluent concentrations of organic material. At elevated SRTs, the
      soluble microbial products resulting from biomass turnover are shown to represent
      the main fraction of soluble organic material in the effluent of the reactor,
      limiting treatment efficiency.

PMID- 12794281
TI  - Modeling of anaerobic degradation of solid slaughterhouse waste: inhibition
      effects of long-chain fatty acids or ammonia.
AB  - The anaerobic bioconversion of solid poultry slaughterhouse wastes was
      kinetically investigated. The modified version of <METHANE> simulation model was
      applied for description of experimental data in mesophilic laboratory digester
      and assays. Additionally, stages of formation and consumption of long chain fatty
      acids (LCFA) were included in the model. Batch data on volatile solids, ammonium,
      acetate, butyrate, propionate, LCFA concentrations, pH level, cumulative volume,
      and methane partial pressure were used for model calibration. As a reference, the
      model was used to describe digestion of solid sorted household waste. Simulation
      results showed that an inhibition of polymer hydrolysis by volatile fatty acids
      and acetogenesis by NH3 or LCFA could be responsible for the complex system
      dynamics during degradation of lipid- and protein-rich wastes.

PMID- 12794282
TI  - Extension of Anaerobic Digestion Model No. 1 with processes of sulfate reduction.
AB  - In the present work, the Anaerobic Digestion Model No. 1 (ADM1) for computer
      simulation of anaerobic processes was extended to the processes of sulfate
      reduction. The upgrade maintained the structure of ADM1 and included additional
      blocks describing sulfate-reducing processes (multiple reaction stoichiometry,
      microbial growth kinetics, conventional material balances for ideally mixed
      reactor, liquid-gas interactions, and liquid-phase equilibrium chemistry). The
      extended model was applied to describe a longterm experiment on sulfate reduction
      in a volatile fatty acid-fed upflow anaerobic sludge bed reactor and was
      generally able to predict the outcome of competition among acetogenic bacteria,
      methanogenic archaea, and sulfate- reducing bacteria for these substrates. The
      computer simulations also showed that when the upward liquid velocity in the
      reactor exceeds 1 m/d, the structure of the sludge becomes essential owing to
      bacterial detachment.

PMID- 12794283
TI  - Parameter identification of thermophilic anaerobic degradation of valerate.
AB  - The considered mathematical model of the decomposition of valerate presents three
      unknown kinetic parameters, two unknown stoichiometric coefficients, and three
      unknown initial concentrations for biomass. Applying a structural identifiability
      study, we concluded that it is necessary to perform simultaneous batch
      experiments with different initial conditions for estimating these parameters.
      Four simultaneous batch experiments were conducted at 55 degrees C, characterized
      by four different initial acetate concentrations. Product inhibition of valerate
      degradation by acetate was considered. Practical identification was done
      optimizing the sum of the multiple determination coefficients for all measured
      state variables and for all experiments simultaneously. The estimated values of
      kinetic parameters and stoichiometric coefficients were characterized by the
      parameter correlation matrix, the confidence interval, and the student's t-test
      at 5% significance level with positive results except for the saturation
      constant, for which more experiments for improving its identifiability should be
      conducted. In this article, we discuss kinetic parameter estimation methods.

PMID- 12794284
TI  - Dynamic simulation of pH in anaerobic processes.
AB  - With the objective of contributing to the buildup of mathematical tools for
      anaerobic process simulation, an algorithm for the dynamic simulation of pH was
      developed. The dynamic simulation of the gaseous phase variables was also
      considered. The pH algorithm was validated for a watery system, obtaining good
      agreement between predicted and experimental data. The applied methodology
      provides a differential equation that allows the inclusion of pH as a state
      variable of the system that can be easily included in a general mathematical
      model of anaerobic digestion using matrix notation. This methodology also allows
      a noticeable decrease in computing time in simulations. A dynamic anaerobic
      digestion model of complex substrates taken from the literature was completed
      with the developed algorithms, and it was used to predict the response of an
      anaerobic reactor against overloading and against the presence of pH-dependent
      inhibitors with satisfactory results.

PMID- 12794285
TI  - Sustainable treatment and reuse of diluted pig manure streams in Russia: from
      laboratory trials to full-scale implementation.
AB  - This article summarizes the results obtained during the laboratory and pilot
      development of integrated biologic and physicochemical treatment and reuse of
      diluted pig manure streams. The application of a straw filter was an effective
      means to separate the solid and liquid fractions of raw wastewater and resulted
      in the removal of a significant part of the dry matter, total nitrogen, and
      phosphorus (65, 27, and 32%, respectively). From the filtrate generated, 60-80%
      of the total chemical oxygen demand (COD) was removed in an upflow anaerobic
      sludge bed reactor operating at 15-30 degrees C. Ammonia was efficiently
      eliminated (>99%) from the anaerobic effluents using Ural laumantite as an ion
      exchanger. However, the nitrogen-content of the zeolite was too low to consider
      this method of ammonia removal economically feasible. The phosphate precipitation
      block, consisting of stripper of CO2 and fluidized-bed crystallizator, was able
      to decrease the concentration of soluble phosphate in the anaerobic effluents up
      to 7-15 mg of phosphate/L. The application of aerobic/anoxic biofilter as a sole
      polishing step was acceptable from an aesthetic point of view (the effluents were
      transparent and almost colorless and odorless) and elimination of biochemical
      oxygen demand (the resting COD was hardly biodegradable). However, the effluent
      nutrient concentrations (especially nitrogen) were far from the current standards
      for direct discharge of treated wastewater. We discuss the approaches for further
      improvement of effluent quality. Finally, we provide an outline of a full-scale
      system that partially implements the laboratory- and pilotscale results obtained.

PMID- 12794286
TI  - Codigestion of manure and organic wastes in centralized biogas plants: status and
      future trends.
AB  - Centralized biogas plants in Denmark codigest mainly manure, together with other
      organic waste such as industrial organic waste, source sorted household waste,
      and sewage sludge. Today 22 large-scale centralized biogas plants are in
      operation in Denmark, and in 2001 they treated approx 1.2 million tons of manure
      as well as approx 300,000 of organic industrial waste. Besides the centralized
      biogas plants there are a large number of smaller farm-scale plants. The long
      term energy plan objective is a 10-fold increase of the 1998 level of biogas
      production by the year 2020. This will help to achieve a target of 12-14% of the
      national energy consumption being provided by renewable energy by the year 2005
      and 33% by the year 2030. A major part of this increase is expected to come from
      new centralized biogas plants. The annual potential for biogas production from
      biomass resources available in Denmark is estimated to be approx 30 Peta Joule
      (PJ). Manure comprises about 80% of this potential. Special emphasis has been
      paid to establishing good sanitation and pathogen reduction of the digested
      material, to avoid risk of spreading pathogens when applying the digested manure
      as fertilizer to agricultural soils.

PMID- 12794287
TI  - Reducing waste contamination from animal-processing plants by anaerobic
      thermophilic fermentation and by flesh fly digestion.
AB  - There is currently no market in Israel for the large amounts of waste from fish-
      and poultry-processing plants. Therefore, this waste is incinerated, as part of
      the measures to prevent the spread of pathogens. Anaerobic methanogenic
      thermophilic fermentation (AMTF) of wastes from the cattle-slaughtering industry
      was examined previously, as an effective system to treat pathogenic bacteria, and
      in this article, we discuss a combined method of digestion by thermophilic
      anaerobic bacteria and by flesh flies, as a means of waste treatment. The AMTF
      process was applied to the wastes on a laboratory scale, and digestion by rearing
      of flesh fly (Phaenicia sericata) and housefly (Musca domestica) larvae on the
      untreated raw material was done on a small scale and showed remarkable weight
      conversion to larvae. The yield from degradation of poultry waste by flesh fly
      was 22.47% (SD = 3.89) and that from fish waste degradation was 35.34% (SD =
      12.42), which is significantly higher than that from rearing houseflies on a
      regular rearing medium. Bacterial contents before and after thermophilic
      anaerobic digestion, as well as the changes in the chemical composition of the
      components during the rearing of larvae, were also examined.

PMID- 12794288
TI  - Pretreatment of swine wastewater using anaerobic filter.
AB  - Efforts were made to assess the efficiency of an anaerobic filter packed with
      porous floating ceramic media and to identify the optimum operational condition
      of anaerobic filter as a pretreatment of swine wastewater for the subsequent
      biological removal of nitrogen and phosphorus. A stepwise decrease in hydraulic
      retention time (HRT) and an increase in organic loading rate (OLR) were utilized
      in an anaerobic filter reactor at mesophilic temperature (35 degrees C). The
      optimum operating condition of the anaerobic filter was found to be at an HRT of
      1 d. A soluble chemical oxygen demand (COD) removal efficiency of 62% and a total
      suspended solids removal efficiency of 39% at an HRT of 1 d were achieved with an
      OLR of 16.0 kg total COD/(m3.d), respectively. The maximum methane production
      rate approached 1.70 vol of biogas produced per volume of reactor per day at an
      HRT of 1 d. It was likely that the effluent COD/total Kjeldahl nitrogen ratio of
      22, the COD/total phosphorous ratio of 47, and the high effluent alkalinity >2500
      mg/L as CaCO3 of the anaerobic filter operated at an HRT of 1 d was adequate for
      the subsequent biological removal of nitrogen and phosphorus.

PMID- 12794289
TI  - Anaerobic treatment of animal byproducts from slaughterhouses at laboratory and
      pilot scale.
AB  - Different mixtures of animal byproducts, other slaughterhouse waste (i.e., rumen,
      stomach and intestinal content), food waste, and liquid manure were codigested at
      mesophilic conditions (37 degrees C) at laboratory and pilot scale. Animal
      byproducts, including blood, represent 70-80% of the total biogas potential from
      waste generated during slaughter of animals. The total biogas potential from
      waste generated during slaughter is about 1300 MJ/cattle and about 140 MJ/pig.
      Fed-batch digestion of pasteurized (70 degrees C, 1 h) animal byproducts resulted
      in a fourfold increase in biogas yield (1.14 L/g of volatile solids [VS])
      compared with nonpasteurized animal byproducts (0.31 L/g of VS). Mixtures with
      animal byproducts representing 19-38% of the total dry matter were digested in
      continuous-flow stirred tank reactors at laboratory and pilot scale. Stable
      processes at organic loading rates (OLRs) exceeding 2.5 g of VS/(L.d) and
      hydraulic retention times (HRTs) less than 40 d could be obtained with total
      ammonia nitrogen concentrations (NH4-N + NH3-N) in the range of 4.0-5.0 g/L.
      After operating one process for more than 1.5 yr at total ammonia nitrogen
      concentrations >4 g/L, an increase in OLR to 5 g of VS/(L.d) and a decrease in
      HRT to 22 d was possible without accumulation of volatile fatty acids.

PMID- 12794290
TI  - Codigestion of proteinaceous industrial waste.
AB  - Organic wastes are increasingly collected source separated, thus requiring
      additional treatment or recovery capacities for municipal biowastes, organic
      industrial wastes, as well as agroindustrial byproducts. In this study, we
      demonstrate that anaerobic digestion is preferentially suited for highwater-
      containing liquid or pasty waste materials. We also evaluate the suitability of
      various organic wastes and byproducts as substrates for anaerobic digestion and
      provide a current status survey of codigestion. Biodegradation tests and
      estimations of the biogas yield were carried out with semisolid and pasty
      proteins and lipids containing byproducts from slaughterhouses; pharmaceutical,
      food, and beverage industries; distilleries; and municipal biowastes. Biogas
      yields in batch tests ranged from 0.3 to 1.36 L/g of volatile solidsadded. In
      continuous fermentation tests, hydraulic retention times (HRTs) between 12 and 60
      d, at a fermentation temperature of 35 degrees C, were required for stable
      operation and maximum gas yield. Laboratory experiments were scaled up to full
      scale codigestion trials in municipal and agricultural digestion plants. Up to
      30% cosubstrate addition was investigated, using municipal sewage sludge as well
      as cattle manure as basic substrate. Depending on addition rate and cosubstrate
      composition, the digester biogas productivity could be increased by 80-400%.
      About 5-15% cosubstrate addition proved to be best suited, without causing any
      detrimental effects on the digestion process or on the further use of the
      digestate.

PMID- 12794291
TI  - The reaction front hypothesis in solid-state digestion: estimation of minimum
      size of viable seed body.
AB  - An alternative mechanism for the anaerobic digestion of a bed of solids was
      recently proposed. A multizoned reaction front might form around a suitable body
      of seed material, then advance through the bed, within the solid phase. Such a
      solid-phase mechanism might coexist with liquid-phase digestion but one or the
      other of these two parallel mechanisms might generally be dominant. It is
      envisaged that solid-phase digestion would be favored by the presence of viable
      seed bodies: single particles of a suitable seed material above a minimum size or
      equivalent aggregates. A key determinant of the feasibility of this mechanism is
      expected to be the minimum viable size for a seed body (dmin). This would depend
      on the thickness of the reaction zones, some of which must initially be
      accommodated within the seed body. In this article, we present some theoretical
      estimates of dmin, which indicate a magnitude of 7-700 mm. Such values suggest
      that solid-phase digestion might be the norm in semi-dry waste digesters. Such
      digestion might be rare in unseeded landfills but it would appear likely that it
      could easily be initiated by suitable seeding.

PMID- 12794292
TI  - Two-step upflow anaerobic sludge bed system for sewage treatment under
      subtropical conditions with posttreatment in waste stabilization ponds.
AB  - A pilot-scale sewage treatment system consisting of two upflow anaerobic sludge
      bed (UASB) reactors followed by five waste stabilization ponds (WSPs) in series
      was studied under subtropical conditions. The first UASB reactor started up in
      only 1 mo (stable operation, high chemical oxygen demand [COD] removal
      efficiency, low volatile fatty acids concentration in the effluent, alkalinity
      ratio above 0.7, biogas production above 0.1 Nm3/kg of CODremoved). Removal
      efficiencies up to 90% were obtained in the anaerobic steps at a hydraulic
      retention time of 6 + 4 h (80% removal in the first step). Fecal coliform removal
      in the whole system was 99.9999% (99.94% in anaerobic steps and 99.98% in WSPs).
      COD balances over UASB reactors are provided. A minimum set of data necessary to
      build COD balances is proposed. Intermittent sludge washout was detected in the
      reactors with the COD balances. Sludge washout from single-step UASB reactors
      should be monitored and minimized in order to ensure constant compliance with
      discharge standards, especially when no posttreatment is provided. The system
      combined high COD and fecal coliform removal efficiency with an extremely low
      effluent concentration, complying with discharge standards, and making it an
      attractive option for sewage treatment in subtropical regions.

PMID- 12794293
TI  - Removal of chemical oxygen demand, nitrogen, and heavy metals using a sequenced
      anaerobic-aerobic treatment of landfill leachates at 10-30 degrees C.
AB  - As a first step of treatment of landfill leachates (total chemical oxygen demand
      [COD]: 1.43-3.81 g/L; total nitrogen: 90-162 mg/L), performance of laboratory
      upflow anaerobic sludge bed reactors was investigated under mesophilic (30
      degrees C), submesophilic (20 degrees C), and psychrophilic (10 degrees C)
      conditions. Under hydraulic retention times (HRTs) of about 0.3 d, when the
      average organic loading rates (OLRs) were about 5 g of COD/(L.d), the total COD
      removal accounted for 81% (on average) with the effluent concentrations close to
      the anaerobic biodegradability limit (0.25 g of COD/L) for mesophilic and
      submesophilic regimes. The psychrophilic treatment conducted under an average HRT
      of 0.34 d and an average OLR of 4.22 g of COD/(L.d) showed a total COD removal of
      47%, giving effluents (0.75 g of COD/L) more suitable for subsequent biologic
      nitrogen removal. All three anaerobic regimes used for leachate treatment were
      quite efficient for elimination of heavy metals (Fe, Zn, Cu, Pb, Cd) by
      concomitant precipitation in the form of insoluble sulfides inside the sludge
      bed. The application of aerobic/ anoxic biofilter as a sole polishing step for
      psychrophilic anaerobic effluents was acceptable for elimination of biodegradable
      COD and nitrogen approaching the current standards for direct discharge of
      treated wastewater.

PMID- 12794294
TI  - Anaerobically treated wastewater in agricultural irrigation as an alternative for
      posttreatment in water-demanding zones.
AB  - Agroindustries usually produce high amounts of wastewaters and are frequently
      located close to agricultural activities. Agricultural use of treated wastewaters
      therefore represents a unique opportunity to solve the problem of water supply
      for irrigation and disposal of treated water at the same time. This article is
      the result of collaborative work with the biggest Chilean pisco- (a distillated
      drink prepared from Muscatel wine) producing company at present. Experiments were
      conducted to establish anaerobic treatability of wastewaters and also irrigation
      properties of treated water. With the purpose of confirming laboratory results, a
      full-scale anaerobic plant was built, and treated water is being used to irrigate
      3000 eucalypti. The results showed, at both laboratory and full scale, that
      anaerobic treatment is suitable for the treatment of pisco wastewater, and that
      nutrient content of treated water can be beneficial for plant growth, reducing
      the need for fertilizers.

PMID- 12794295
TI  - Reductive decolorization of a textile reactive dyebath under methanogenic
      conditions.
AB  - The objective of the present study was to assess the biological decolorization of
      an industrial, spent reactive dyebath and its three dye components (Reactive Blue
      19 [RB 19], Reactive Blue 21 [RB 21], and Reactive Red 198 [RR 198]) under
      methanogenic conditions. Using a mixed, methanogenic culture, batch assays were
      performed to evaluate the rate and extent of color removal as well as any
      potential toxic effects. Overall, a high rate and extent of color removal (>10
      mg/[L.h] and 88%, respectively) were observed in cultures amended with either RB
      19 (an anthraquinone dye) or spent dyebath at an initial dye concentration of 300
      mg/L (expressed as RB 19 equivalent) and 30 g/L of NaCl. Inhibition of
      acidogenesis and, to a larger degree, of methanogenesis resulting in accumulation
      of volatile fatty acids was observed in both RB 19- and spent dyebath-amended
      cultures. RB 21 (a phthalocyanine dye) and RR 198 (an azo dye) tested at an
      initial concentration of 300 mg/L did not result in any significant inhibition of
      the mixed methanogenic culture. Based on results obtained with cultures amended
      with RB 19 with and without NaCl, as well as a control culture amended with 30
      g/L of NaCl, salt was less inhibitory than either RB 19 or the dyebath.
      Therefore, the toxic effect of the spent dyebath is at least partially attributed
      to its major dye component RB 19 and NaCl. Further testing of the effect of RB 19
      decolorization products on the methanogenic activity in the absence of NaCl
      demonstrated that these products are much less inhibitory than the parent dye.
      Although color removal occurred despite the severe culture inhibition, biological
      decolorization of full-strength reactive spent dyebaths using methanogenic
      cultures in a repetitive, closed-loop system is not deemed feasible. For this
      reason, a fermentative and halotolerant culture was developed and successfully
      used in our laboratory for the decolorization of industrial reactive dyebaths
      with 100 g/L of NaCl.

PMID- 12794296
TI  - Electron beam pretreatment of sewage sludge before anaerobic digestion.
AB  - The pretreatment of waste-activated sludge (WAS) by electron beam irradiation was
      studied in order to improve anaerobic sludge digestion. The irradiation dose of
      the electron beam was varied from 0.5 to 10 kGy. Batch and continuous-flow
      stirred tank reactors (CFSTRs) were operated to evaluate the effect of the
      electron beam pretreatment on anaerobic sludge digestion. Approximately 30-52% of
      the total chemical oxygen demand (COD) content of the WAS was solubilized within
      24 h after electron beam irradiation. A large quantity of soluble COD, protein,
      and carbohydrates leached out from cell ruptures caused by the electron beam
      irradiation. Volatile fatty acids production from the irradiated sludge was
      approx 90% higher than that of the unirradiated sludge. The degradation of
      irradiated sewage sludge was described by two distinct first-order decay rates
      (k1 and k2). Most initial decay reaction accelerated within 10 d, with an average
      k1 of 0.06/d for sewage sludge irradiated at all dosages. The mean values for the
      long-term batch first-order decay coefficient (k2) were 0.025/d for irradiated
      sewage sludge and 0.007/d for unirradiated sludge. Volatile solids removal
      efficiency of the control reactor fed with unirradiated sewage sludge at a
      hydraulic retention time (HRT) of 20 d was almost the same as that of the CFSTRs
      fed with irradiated sludge at an HRT of 10 d. Therefore, disintegration of sewage
      sludge cells using electron beam pretreatment could reduce the reactor solid
      retention time by half.

PMID- 12794297
TI  - Anaerobic waste stabilization ponds: a low-cost contribution to a sustainable
      wastewater reuse cycle.
AB  - Waste stabilization ponds (WSP) have been used extensively all over Europe over
      the last 50 yr for the treatment of municipal and industrial wastewaters. Models
      presented in manuals should be used only for guidance, and local experience from
      pilot and full-scale plants of a particular pond type is extremely valuable.
      Anaerobic WSP are single-stage, continuous- flow, anaerobic reactors operating at
      ambient temperatures and low volumetric organic loading as a pretreatment method.
      This article presents a literature review on the different available operational
      parameters of anaerobic ponds and examples from full-scale plant performance
      worldwide. On a wastewater management scheme, involving reuse for agriculture,
      the zero-energy demand of a waste stabilization pond series for the effective
      removal of organic and microbiological loading under existing legislation and
      guidelines will remain a valuable tool for sustainable development.

PMID- 12794298
TI  - Combined biologic (anaerobic-aerobic) and chemical treatment of starch industry
      wastewater.
AB  - A combined biologic and chemical treatment of high-strength (total chemical
      oxygen demand [CODtot] up to 20 g/L), strong nitrogenous (total N up to 1 g/L),
      and phosphoric (total P up to 0.4 g/L) starch industry wastewater was
      investigated at laboratory-scale level. As a principal step for COD elimination,
      upflow anaerobic sludge bed reactor performance was investigated at 30 degrees C.
      Under hydraulic retention times (HRTs) of about 1 d, when the organic loading
      rates were higher than 15 g of COD/(L.d), the CODtot removal varied between 77
      and 93%, giving effluents with a COD/N ratio of 4-5:1, approaching the
      requirements of subsequent denitrification. The activated sludge reactor
      operating in aerobic-anoxic regime (HRT of about 4 d, duration of aerobic and
      anoxic phases of 30 min each) was able to remove up to 90% of total nitrogen and
      up to 64% of COD tot from the anaerobic effluents under 17-20 degrees C. The
      coagulation experiments with Fe(III) showed that 1.4 mg of resting hardly
      biodegradable COD and 0.5 mg of phosphate (as P) could be removed from the
      aerobic effluents by each milligram of iron added.

PMID- 12794299
TI  - Production and energetic use of biogas from energy crops and wastes in Germany.
AB  - The production of biogas for reducing fossil CO2 emissions is one of the key
      strategic issues of the German government and has resulted in the development of
      new process techniques and new technologies for the energetic use of biogas.
      Progress has been made in cultivating energy crops for biogas production, in
      using new reactor systems for anaerobic digestion, and in applying more efficient
      technologies for combined heat and power production. Recently, integration of
      fuel cells within the anaerobic digestion process was started, and new
      technologies for biogas upgrading and conversion to hydrogen were tested. This
      article describes the trends in Germany for achieving more efficient energy
      production.

PMID- 12794300
TI  - Development and use of an economic evaluation model to assess establishment of
      local centralized rural biogas plants in Greece.
AB  - An economic evaluation model was developed in the Laboratory of Agricultural
      Structures (LAS) of the Agricultural University of Athens-the Modified Basic
      Economic Evaluation Model (MBEEM). This model is an improved version of the
      original Basic Economic Evaluation Model, available in LAS, and it is used to
      assess the cost-effectiveness of biogas production systems. Because of the
      parameters involved, a computer model was developed to facilitate the application
      of the MBEEM. The model was used in this work to determine the cost-effective
      size of a local centralized biogas production system fed with pig wastes.

PMID- 12794301
TI  - Aerobic and anaerobic microbial degradation of poly-beta-hydroxybutyrate produced
      by Azotobacter chroococcum.
AB  - Food industry wastewater served as a carbon source for the synthesis of poly-beta
      hydroxybutyrate (PHB) by Azotobacter chroococcum. The content of polymer in
      bacterial cells grown on the raw materials reached 75%. PHB films were degraded
      under aerobic, microaerobic, and anaerobic conditions in the presence and absence
      of nitrate by microbial populations of soil, sludges from anaerobic and
      nitrifying/denitrifying reactors, and sediment from a sludge deposit site.
      Changes in molecular mass, crystallinity, and mechanical properties of PHB were
      studied. Anaerobic degradation was accompanied by acetate formation, which was
      the main intermediate utilized by denitrifying bacteria or methanogenic archaea.
      On a decrease in temperature from 20 to 5 degrees C in the presence of nitrate,
      the rate of PHB degradation was 7.3 times lower. Under anaerobic conditions and
      in the absence of nitrate, no PHB degradation was observed, even at 11 degrees C.
      The enrichment cultures of denitrifying bacteria obtained from soil and anaerobic
      sludge degraded PHB films for a short time (3-7 d). The dominant species in the
      enrichment culture from soil were Pseudomonas fluorescens and Pseudomonas
      stutzeri. The rate of PHB degradation by the enrichment cultures depended on the
      polymer molecular weight, which reduced with time during biodegradation.

PMID- 12794302
TI  - Alpha-synuclein: its biological function and role in neurodegenerative diseases.
AB  - Alpha-synuclein is regarded as a presynaptic protein, which may play an important
      role in neuronal plasticity. However, the actual physiological function of this
      protein is not completely clear. Abnormal accumulation of fibrillar alpha
      synuclein in Lewy bodies, as well as mutations in the alpha-synuclein gene
      identified in the familial forms of Parkinson's disease, point to a central role
      of this protein in the pathophysiology of Lewy body-related disorders. In vivo
      and in vitro studies showed that overexpression of alpha-synuclein, its
      aggregation, and interaction with other proteins are the most critical factors
      affecting the survival of neurons. In Alzheimer's disease, the amount of alpha
      synuclein is found to be elevated at synapses, whereas a peptide derived from
      alpha-synuclein is thought to represent an intrinsic component of amyloid
      plaques. It is likely that in this disorder alpha-synuclein plays a dual role by
      being involved not only in synaptic function but also in amyloid beta
      fibrillogenesis.

PMID- 12794303
TI  - Knockout of p75NTR does not alter the viability of striatal neurons following a
      metabolic or excitotoxic injury.
AB  - Following metabolic or excitotoxic injury to the striatum, there is de novo
      expression of the low-affinity p75 neurotrophin receptor (p75NTR). The novel
      expression of this pan neurotrophin receptor in rodents occurs within the lesion
      core and surrounding area, creating a division between viable and nonviable
      tissue. The present series of experiments sought to elucidate whether the p75NTR
      expression seen following metabolic and excitotoxic injury alters neuronal
      viability within the striatum. Toward this end, we compared the extent of
      striatal lesion created with quinolinic acid (QA) or 3-nitropropionic acid (3-NP)
      in p75NTR null and wild-type mice. Using stereological techniques, we found that
      the lesion volume and neuronal cell counts between p75NTR null and wild-type mice
      were similar 1, 2, and 4 weeks post-QA or -3-NP lesion. The results indicate that
      the expression of p75NTR within reactive astrocytes in the mouse striatum is not
      a key factor in protecting neuronal cell death following metabolic and
      excitotoxic insults.

PMID- 12794304
TI  - Domain-dependent modulation of PDGFRbeta by ganglioside GM1.
AB  - The regulation of receptor tyrosine kinases (RTKs) is important in several
      cellular events, including proliferation, differentiation, and apoptosis.
      Gangliosides are sialic acid-containing glycosphingolipids that can regulate RTK
      activity. The addition of ganglioside GM1 to the medium of Swiss 3T3 fibroblasts
      inhibits both platelet-derived growth factor (PDGF)-mediated tyrosine
      phosphorylation of PDGF receptor beta (PDGFRbeta) and receptor-mediated
      endocytosis. However, GM1 did not affect PDGF-mediated receptor phosphorylation,
      neuritogenesis, or endocytosis in PC12 cells stably transfected with the gene for
      PDGFRbeta. The ability of GM1 to modulate PDGFRbeta in 3T3 cells but not in
      transfected PC12 cells indicates a cell context-dependent response. We
      hypothesized that this inhibition of PDGFRbeta by GM1 must map to one or more
      domains of the receptor. Thus, a chimeric receptor was created that possessed the
      extracellular and transmembrane domains of the nerve growth factor (NGF) receptor
      TrkA and the cytoplasmic domain of PDGFRbeta (TTbeta). In 3T3 cells transfected
      with the TTbeta construct, GM1 did not inhibit NGF-induced tyrosine
      phosphorylation of the chimeric receptor or of Erk1/2 in this cell line. GM1
      still inhibited PDGF-mediated tyrosine phosphorylation of endogenous PDGFRbeta
      and of Erk1/2 in Swiss TTbeta cells. Thus, the cytoplasmic domain of PDGFRbeta is
      not required for GM1-dependent inhibition of PDGFRbeta in 3T3 cells. This
      suggests that the inhibition of PDGFRbeta by GM1 in Swiss 3T3 fibroblasts maps to
      either the extracellular and/or transmembrane domain of PDGFRbeta.

PMID- 12794305
TI  - Conserved cholecystokinin receptor transmembrane domain IV amino acids confer
      peptide affinity.
AB  - The Cholecystokinin type 1 and type 2 receptors (CCK-1R and CCK-2R) share >50%
      amino acid identity, as well as subnanomolar affinity for the endogenous peptide
      cholecystokinin octapeptide (CCK-8). Although it is likely that these two
      receptor subtypes share amino acids that confer CCK-8 affinity, it has been
      difficult to identify such residues. We have examined the role of several
      transmembrane domain (TMD) IV residues that are common to both CCK receptor
      subtypes. In both the CCK-1R and CCK-2R, we demonstrate that alanine substitution
      of two TMD IV residues, which are highly conserved among all known CCK receptor
      subtypes and species homologs, significantly decrease CCK-8 affinity. Despite the
      observed decrease in peptide binding, the mutant receptors maintain close to wild
      type affinity for the respective subtype selective nonpeptide ligands, 3H-labeled
      L-364,714 (CCK-1R) and 3H-labeled L-365,260 (CCK-2R), suggesting conserved
      tertiary structure of these mutants. Assessment of CCK-8-induced inositol
      phosphate production at each of the mutant CCK receptors revealed normal peptide
      efficacy. In contrast, peptide potencies are reduced in parallel with the
      observed decreases in affinity. Taken together, these findings suggest that
      important peptide affinity determinants are localized on TMD IV, a region that
      has not previously been considered a major contributor to ligand affinity in
      either CCK receptors or other G protein-coupled peptide receptors.

PMID- 12794306
TI  - Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine
      colostrum.
AB  - In previous studies we showed that colostrinin (CLN), a complex of proline-rich
      polypeptides derived from ovine colostrum, induces mitogenic stimulation, as well
      as a variety of cytokines in human peripheral blood leukocytes, and possesses
      antioxidant activity in pheochromocytoma (PC12) cells. In this study we
      investigated the effects of CLN on 4-hydroxynonenal (4HNE)-mediated adduct
      formation, generation of reactive oxygen species (ROS), glutathione (GSH)
      metabolism, and the modification of signal transduction cascade that leads to
      activation of c-Jun N-terminal kinase (JNK) in PC12 cells. Here we demonstrate
      that CLN (1) reduced the abundance of 4HNE-protein adducts, as shown by
      fluorescent microscopy and Western blot analysis; (2) reduced intracellular
      levels of ROS, as shown by a decrease in 2',7'-dichlorodihydro-fluorescein
      mediated fluorescence; (3) inhibited 4HNE-mediated GSH depletion, as determined
      fluorimetrically; and (4) inhibited 4HNE-induced activation of JNKs. Together,
      these findings suggest that CLN appears to down-regulate 4HNE-mediated lipid
      peroxidation and its product-induced signaling that otherwise may lead to
      pathological changes at the cellular and organ level. These findings also suggest
      further that CLN could be useful in the treatment of diseases such as
      Alzheimer's, as well as those in which ROS are implicated in pathogenesis.

PMID- 12794307
TI  - Inhibition of serotonin re-uptake by licorice constituents.
AB  - Ovarian steroid hormones, estrogen and progestin, affect the function of the
      serotonin neural system by inhibiting serotonin re-uptake through allosteric
      interaction with the serotonin transporter (SERT) in a nongenomic mechanism.
      Blocking or reducing serotonin re-uptake at the synapse alleviates depression.
      The aim of this study was to test the effect of compounds of the isoflavan and
      isoflavene groups, subclasses of the flavonoids family, on serotonin re-uptake
      and to compare the results with the effect of other known phytoestrogens like
      genistein and daidzein to relate the activity of these compounds to their
      structure. The effect of these compounds on the re-uptake of radioactive
      serotonin was assayed in HEK-293 cells stably expressed the recombinant human
      serotonin transporter (hSERT). The results demonstrated that the isoflavans
      glabridin and 4'-O-methylglabridin (4'-OMeG) and the isoflavene glabrene
      inhibited serotonin re-uptake by 60, 53 and 47%, respectively, at 50 microM,
      whereas resorcinol, the isoflavan 2'-O-methylglabridin (2'-OMeG), and the
      isoflavones genistein and daidzein were inactive. The inhibition of serotonin re
      uptake is dose dependant with glabridin and estradiol. These results emphasize
      the importance of the lipophilic part of the isoflavans, as well as the hydroxyl
      at position 2' on ring B. In conclusion, this study showed that several
      isoflavans are unique phytoestrogens, which like estradiol, affects the
      serotonergic system and inhibits serotonin re-uptake and, thus, potentially may
      be beneficial for mild to moderate depression in pre- and postmenopausal women.

PMID- 12794308
TI  - The role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary
      levels.
AB  - The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and
      its mRNAin the three levels of the hypothalamo-hypophyseal-ovarian axis was
      previously demonstrated using immunohistochemistry, in situ hybridization, and
      reverse transcriptase polymerase chain reaction (RT-PCR). In the hypothalamus,
      PACAP is present in neuroendocrine effector cells and in the median eminence. In
      the anterior pituitary and ovary, PACAP is transiently present during the
      proestrous stage of the estrous cycle. In the pituitary, PACAP was observed in
      gonadotropes. In the ovary, PACAP was demonstrated in the granulosa cells of the
      preovulatory ovarian follicles. The effect of PACAP on luteinizing hormone (LH)
      secretion was demonstrated in in vivo and in vitro models. In our work we have
      studied the role of PACAP in gonadotropic hormone secretion at hypothalamic and
      pituitary levels. At the hypothalamic level, PACAP, administered
      intracerebroventricularly to female rats before the critical period of the
      proestrus stage, can inhibit LH release and ovulation. Its inhibiting effect is
      mediated through corticotropin-releasing factor (CRF) and endogenous opioids.
      PACAP administered to neonatal female rats delayed the onset of puberty by
      influencing the luteinizing hormone-releasing hormone (LHRH) neuronal system. In
      the pituitary gland, the release of PACAP depended on the stage of the estrous
      cycle and on the time of day the animals were sacrificed. On the day of
      proestrus, the number of PACAP-releasing cells showed a diurnal change with two
      peaks (in the morning and in the evening). The peak was much higher in the
      evening at the end of the LH surge than in the morning.

PMID- 12794309
TI  - Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase
      activating polypeptide receptors in chick cerebral cortex.
AB  - In this study receptors for vasoactive intestinal peptide (VIP) and pituitary
      adenylate cyclase-activating polypeptide (PACAP) were characterized in chick
      cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]
      VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical
      membranes was found to be rapid, stable, saturable, reversible, and of high
      affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting
      binding to a single class of receptor binding sites with high affinity (Kd = 0.21
      nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of
      potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum
      was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 >> VIP6-28
      (mammalian) > PHI (porcine) >> neurotensin6-11-chicken VIP7-28 > neurotensin6-11
      mammalian VIP7-28 >>> VIP16-28 (chicken; inactive) approximately secretin
      (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were
      sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded
      that the cerebral cortex of chick, in addition to PAC1 receptors, contains a
      population of VPAC-type receptors.

PMID- 12794310
TI  - Antagonism of VIP-stimulated cyclic AMP formation in chick brain.
AB  - Of eight peptides tested (0.01-5 microM), only two, that is, pituitary adenylate
      cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal
      peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral
      cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at
      the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6
      27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7
      28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute
      preincubation of chick cortical slices with 5 microM PACAP6-27, NT-cVIP, or NT
      mVIP competitively antagonized the cAMP effects of cVIP (0.03-1 microM), with the
      truncated form of PACAP being the best antagonist. Preincubation of slices with 5
      microM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 microM)
      induced increase in cAMP production; however its action was independent of the
      concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic
      activity against the full-length peptide. In parallel experiments, 30-min
      pretreatment of cortical slices with 5 microM PACAP6-27 significantly antagonized
      the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP
      hybrid was ineffective. It has been concluded that in the chick brain, PACAP and
      cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively,
      and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective
      antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may
      represent VPACtype receptor-selective blocking activity.

PMID- 12794312
TI  - Nuclear immunostaining in rat neuronal cells using two anti-Kir2.2 ion channel
      polyclonal antibodies.
AB  - The inwardly rectifying potassium ion channel Kir2.2 has recently been
      demonstrated to have nuclear and plasma membrane subcellular localization.
      Nuclear expression of Kir2.2 is controversial, as a functional role for Kir2.0
      potassium channels in the nucleus has not been investigated. However, in this
      report we have demonstrated Kir2.2 nuclear localization in sections of rat
      hindbrain and dorsal root ganglia tissue, using two anti- Kir2.2 polyclonal
      antisera with different epitope specificities. These data confirm nuclear
      localization and are suggestive of new functions of Kir2.0 potassium ion channels
      in the nucleus.

PMID- 12794311
TI  - MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity
      for dopaminergic neurons.
AB  - We describe the discovery of a novel, 20 kDa, secreted human protein named
      mesencephalic astrocyte-derived neurotrophic factor, or MANF. The homologous,
      native molecule was initially derived from a rat mesencephalic type-1 astrocyte
      cell line and recombinant MANF subcloned from a cDNA encoding human arginine-rich
      protein. MANF selectively protects nigral dopaminergic neurons, versus GABAergic
      or serotonergic neurons. The discovery of MANF marks a more systematic approach
      in the search for astrocyte-derived, secreted proteins that selectively protect
      specific neuronal phenotypes. Compared to glial cell line-derived neurotrophic
      factor (GDNF) and brain-derived neurotrophic factor (BDNF), MANF was more
      selective in the protection of dopaminergic neurons at lower (0.05-0.25 ng/mL)
      and middle (0.5-2.5 ng/mL) concentrations: MANF>GDNF>BDNF. GDNF was more
      selective at higher concentrations (25-50 ng/ml): GDNF>MANF>BDNF. Two domains in
      MANF of 39-AA and 109-AA respectively, and eight cysteines are conserved from C.
      elegans to man. MANF is encoded by a 4.3 Kb gene with 4 exons, and is located on
      the short arm of human chromosome 3. The secondary structure is dominated by
      alpha-helices (47%) and random coils (37%). Studies to determine the localization
      of MANF in the brains of rat, monkey, and man, as well as the receptor, signaling
      pathways, and biologically active peptide mimetics are in progress. The
      selective, neuroprotective effect of MANF for dopaminergic neurons suggests that
      it may be indicated for the treatment of Parkinson's disease.

PMID- 12794313
TI  - Prospect of therapeutic approaches to tauopathies.
AB  - Alois Alzheimer described the concurrence of two conspicuous proteinacious
      aggregates in 1906. Today it is clear that the two types of protein aggregates
      are fundamentally different. One consists of a short fragment (Abeta peptide) of
      a membrane protein APP and is found mainly outside of cells and the other is
      formed from a biochemically modified cytoskeleton-associated protein known as
      tau. The latter is found exclusively inside cells. Aggregated tau in all
      tauopathies including AD is abnormally modified by the excess incorporation of
      chemical groups called phosphates (hyperphosphorylation), and the appearance of
      this biochemical change coincides with the onset all tauopathies, suggesting that
      it is both a necessary and sufficient cause for such diseases. Data indicate that
      the basis for tau hyperphosphorylation is the dysregulation of key enzymes known
      as kinases. These enzymes are therapeutic targets for AD and other
      neurodegenerative diseases, which feature pathological tau structures in brain

PMID- 12794315
TI  - Cu3V10O28.24H2O and CuNa4V10O28.23H2O.
AB  - The crystal structures of tricopper decavanadate tetracosahydrate, (I), and
      copper tetrasodium decavanadate tricosahydrate, (II), have been determined by
      single-crystal X-ray diffraction. Both compounds exhibit a catenary structure
      consisting of [V10O28](6-) anions linked by Cu2+ cations in (I) or by Na+ cations
      in (II). Compound (II) also contains a polymeric linear array of edge-sharing
      [Na(OH2)6](+) and [Cu(OH2)6](2+) octahedra. In both compounds, the [V10O28](6-)
      ions lie about inversion centres and the Cu2+ ions in (I) also lie about
      inversion centers.

PMID- 12794314
TI  - The relationship between amyloid and tau.
AB  - Based on genetic findings, the relationship between the APP/Abeta and tau/tangle
      pathologies are discussed. It is argued that APP/Abeta is upstream of tau/tangle
      in the Alzheimer pathogenesis, and that the relationship between the pathologies
      are promiscuous in two ways: first, APP/Abeta can equally be seen to be upstream
      of synuclein/Lewy bodies in cell death pathways, and second, tau pathology can be
      initiated by genetic lesions in other pathways.

PMID- 12794316
TI  - Raman spectroscopy of silver pertechnetate.
AB  - The title compound, AgTcO4, contains close Ag-O contacts, and Raman spectroscopy
      shows a reduction in the Tc-O stretching frequencies on changing the
      pertechnetate counter-cation from K+ to Ag+.

PMID- 12794317
TI  - A new polytype of orthoboric acid, H(3)BO(3)-3T.
AB  - The crystal structure of H(3)BO(3)-3T, a new trigonal polytype of orthoboric
      acid, consists of sheets of hydrogen-bonded B(OH)(3) molecules similar to those
      found in the triclinic structure of orthoboric acid, H(3)BO(3)-2A. In each case,
      van der Waals forces connect the sheets. However, the stacking sequences of the
      sheets differ between the two polymorphs. In H(3)BO(3)-3T (space group P3(2)),
      the sheets are stacked in the repeating sequence ABC em leader, whereas in
      H(3)BO(3)-2A (space group P-1, the sheets are stacked in the repeating sequence
      AB em leader.

PMID- 12794318
TI  - A new aquahydroxidocopper(II) oxovanadium(IV) vanadate, Cu(H2O)(OH)VO(VO4).
AB  - Single crystals of the title compound have been prepared hydrothermally. Vanadate
      tetrahedra and distorted oxovanadium octahedra form layers, linked by two
      independent Cu atoms located on inversion centres. Each Cu atom is surrounded by
      six O atoms, forming an octahedron distorted by Jahn-Teller elongation. One of
      the two independent interlayer spaces bridged by the Cu atoms is significantly
      more compact than the other.

PMID- 12794319
TI  - A synthetic zinc tellurium oxochloride, Zn2(TeO3)Cl2.
AB  - Single crystals of dizinc tellurium dichloride trioxide, Zn(2)(TeO(3))Cl(2), were
      synthesized via a transport reaction in sealed evacuated glass tubes. The
      compound has a layered structure in which the building units are [ZnO(4)Cl]
      square pyramids, distorted [ZnO(2)Cl(2)] tetrahedra and [TeO(3)E] tetrahedra (E
      is the 5s(2) lone pair of the Te(IV) atom), joined through shared edges and
      corners to form charge-neutral layers. Cl atoms and Te-atom lone pairs protrude
      from the surfaces of each layer towards adjacent layers, and the layers are held
      together by dispersion forces only. The compound is isostructural with the
      synthetic compound CuZn(TeO(3))Cl(2) and the mineral sophiite,
      Zn(2)(SeO(3))Cl(2).

PMID- 12794320
TI  - A mixed-valent niobium oxysulfide, La2Nb3S2O8.
AB  - Dilanthanum triniobium disulfide octaoxide, La(2)Nb(3)S(2)O(8), crystallizes in
      the orthorhombic space group Pnnm and is isostructural with the
      Ln(2)Ta(3)X(2)O(8) (Ln = La, Ce, Pr and Nd, and X = S and Se) family of tantalum
      compounds. Nb(4+) and Nb(5+) ions co-exist in the structure and occupy different
      crystallographic sites. While the Nb(4+) ions are found in mixed oxygen and
      sulfur octahedra, the Nb(5+) ions are found in oxygen-only octahedra.

PMID- 12794321
TI  - KHCoP2O7.2H2O: a novel acidic pyrophosphate.
AB  - Potassium cobalt hydrogenpyrophosphate dihydrate, KHCoP(2)O(7).2H(2)O,
      crystallizes in the orthorhombic space group Pnma. This salt is isotypic with
      KHMP(2)O(7).2H(2)O (M = Mn and Zn). The structure consists of alternating layers,
      built from HP(2)O(7)(3-) acidic pyrophosphate groups and CoO(6) octahedra, joined
      by potassium ions and bridging hydrogen bonds. The Co, K and water O atoms lie on
      mirror planes. The pyrophosphate group consists of two symmetry-related PO(4)
      groups, with the bridging O atom on a mirror plane.

PMID- 12794322
TI  - Bis(4-[N,N-bis(2-cyanoethyl)amino]pyridine-kappaN(1))silver(I) perchlorate, with
      the perchlorate anion located in the cation cavity.
AB  - The title complex, bis[3,3'-(pyridine-4-imino
      kappaN(1))dipropanenitrile]silver(I) perchlorate, [Ag(CEAP)(2)]ClO(4) (CEAP is 4
      [N,N-bis(2-cyanoethyl)amino]pyridine, C(11)H(12)N(4)), has been prepared and
      characterized. The unit cell consists of two crystallographically non-equivalent
      molecules. Cation cavities are constructed by [Ag(CEAP)(2)](+) cations through
      hydrogen bonds, and the ClO(4)(-) anions are incorporated into the cavities in
      mu(4)- and mu(2)-ClO(4)(-) bridging modes through C-H.O hydrogen bonds.

PMID- 12794323
TI  - The layered structure of poly[[di-mu-chloro-bis[chloro(2-ethyltetrazole
      kappaN(4))copper(II)]]-di-mu-2-ethyltetrazole-kappa(2)N(1):N(4)].
AB  - In the polymeric title complex, [CuCl(2)(C(3)H(6)N(4))(2)](n), there are two
      ligands in the asymmetric unit. The Cu atom adopts an elongated octahedral
      geometry, with two 2-ethyltetrazole ligands [Cu-N = 2.0037 (16) and 2.0136 (16)
      A] and two Cl atoms [Cu-Cl = 2.2595 (6) and 2.2796 (6) A] in equatorial
      positions. A Cl atom and a symmetry-related 2-ethyltetrazole molecule [Cu-Cl =
      2.8845 (8) A and Cu-N = 2.851 (2) A] lie in the axial positions of the
      octahedron. One of the two 2-ethyltetrazole ligands of the asymmetric unit
      exhibits bidentate binding to two Cu atoms through two N atoms of the tetrazole
      ring, whereas the other ligand is coordinated in a monodentate fashion via one
      tetrazole N atom. The Cu-atom octahedra form dimer entities by sharing edges with
      equatorial and axial Cl atoms. The dimers are linked together through the 2
      ethyltetrazole ligands to form one-dimensional polymeric zigzag chains extending
      along the b axis. The chains are connected into infinite layers parallel to the
      (10-1) plane via the 2-ethyltetrazole ligands.

PMID- 12794324
TI  - Isostructural or not? Adducts of some aryltin halides with (E)-1,2-bis(4
      pyridyl)ethene.
AB  - The title complexes [mu-(E)-4,4'-(ethene-1,2-diyl)dipyridine
      kappa(2)N:N']bis[halotris(4-methylphenyl)tin(IV)],
      [Sn(2)(C(7)H(7))(6)X(2)(C(12)H(10)N(2))], where halo is chloro (X = Cl) and bromo
      (X = Br) are isostructural. In both crystals, the molecules lie on inversion
      centers, and there are voids of ca 80 A(3) that could, but apparently do not,
      accommodate water molecules. The corresponding iodo structure (X = I) is almost,
      but not quite, isostructural with the other two compounds; when Br is changed to
      I, the length of the c axis decreases by more than 1 A and the voids are no
      longer large enough to accomodate any solvent molecule. The related complex [mu
      (E)-4,4'-(ethene-1,2-diyl)dipyridine-kappa(2)N:N']bis[chlorotriphenyltin(IV)],
      [Sn(2)(C(6)H(5))(6)Cl(2)(C(12)H(10)N(2))], crystallizes in a related structure,
      but the molecules lie on general rather than on special positions. The molecular
      structures of the four complexes are similar, but the conformation of the phenyl
      derivative is approximately eclipsed rather than staggered.

PMID- 12794325
TI  - Ferrocene compounds. XXXVIII. Dimethyl ferrocene-1,1'-dicarboxylate.
AB  - In the title compound, [Fe(C(7)H(7)O(2))(2)], the cyclopentadienyl rings and the
      two attached methoxycarbonyl groups, in an anti arrangement, form an extended pi
      conjugated system. The Fe-C distances range from 2.035 (3) to 2.061 (3) A and the
      average value of the C-C bond lengths in the two cyclopentadienyl rings is 1.419
      (5) A. The rings are almost parallel to one another [1.0 (2) degrees ] and are
      mutually twisted from an eclipsed conformation by only 1.8 (3) degrees (average
      value). The methoxycarbonyl groups are twisted out of the plane of the
      cyclopentadienyl rings by 6.5 (4) and 15.7 (4) degrees, respectively. The
      molecules are joined into dimers by intermolecular C-H.O hydrogen bonds that form
      ten-membered rings. The same types of hydrogen bonds form eight-membered rings
      and infinite chains along the b axis.

PMID- 12794326
TI  - trans-Bis[1,2-bis(diphenylphosphino)ethane-kappa(2)P,P']bis[4
      (trimethylsilyl)buta-1,3-diynyl]ruthenium(II) and trans-bis[1,2
      bis(diphenylphosphino)ethane-kappa(2)P,P']bis(buta-1,3-diynyl)ruthenium(II).
AB  - The crystal structures of the title compounds,
      [Ru(C(7)H(9)Si)(2)(C(26)H(24)P(2))(2)] and [Ru(C(4)H)(2)(C(26)H(24)P(2))(2)], are
      described. The metal centre in both complexes has an octahedral coordination
      geometry, with mutually trans buta-1,3-diynyl ligands forming pseudo-linear
      ruthenium-centred polyyne chains.

PMID- 12794327
TI  - Bis(2-aminopyridine-kappaN(1))(benzoato-kappaO)silver(I).
AB  - In the title compound, [Ag(C(7)H(5)O(2))(C(5)H(6)N(2))(2)], the Ag(I) atom is
      tricoordinated by two independent pyridine N atoms and one benzoate O atom in a
      nearly planar geometry. An intramolecular N-H.O hydrogen bond forms an S(8) graph
      ring. The packing is built from molecular layers stabilized by two types of N-H.O
      hydrogen bond. Intermolecular Ag.N and intramolecular Ag.O contacts were also
      observed, together with three weak intermolecular C-H.pi interactions.

PMID- 12794328
TI  - catena-Poly[[bis[mu-1,2-bis(1-methyltetrazol-5-yl)ethane
      kappa(2)N(4):N(4')]bis[chlorocopper(II)]]-di-mu-chloro].
AB  - In the title compound, [Cu(2)Cl(4)(C(6)H(10)N(8))(2)](n), the ligand has C(2)
      symmetry, and the Cu and Cl atoms lie on a mirror plane. The coordination
      polyhedron of the Cu atom is a distorted square pyramid, with the basal positions
      occupied by two N atoms from two different ligands [Cu-N = 2.0407 (18) A] and by
      the two Cl atoms [Cu-Cl = 2.2705 (8) and 2.2499 (9) A], and the apical position
      occupied by a Cl atom [Cu-Cl = 2.8154 (9) A] that belongs to the basal plane of a
      neighbouring Cu atom. The [CuCl(2)(C(6)H(10)N(8))](2) units form infinite chains
      extending along the a axis via the Cl atoms. Intermolecular C-H.Cl contacts [C.Cl
      = 3.484 (2) A] are also present in the chains. The chains are linked together by
      intermolecular C-H.N interactions [C.N = 3.314 (3) A].

PMID- 12794329
TI  - [Fe(TPP)(4-MePip)(2)]: an axially compressed bis(secondary amine) complex of an
      iron(II) porphyrin.
AB  - The low-spin iron(II) ion of bis(4-methylpiperidine)(5,10,15,20
      tetraphenylporphyrinato)iron(II), [Fe(TPP)(4-MePip)(2)], where TPP is 5,10,15,20
      tetraphenylporphyrinate (C(44)H(28)N(4)) and 4-MePip is 4-methylpiperidine
      (C(6)H(13)N), is located at a center of inversion, and there is one molecule in
      the triclinic unit cell. The axial 4-MePip ligands adopt a chair conformation and
      the alpha-C atoms are oriented at angles of 21.2 (2) and 32.8 (2) degrees
      relative to the closest porphyrin N atoms. The equatorial Fe-N(TPP) distances are
      1.998 (2) and 1.990 (2) A, while the axial Fe-N distance is 2.107 (2) A. The
      relatively short axial coordination distance reflects compression of the molecule
      along its principal axis by intermolecular non-bonded interactions.

PMID- 12794330
TI  - Cobalt(II) and nickel(II) complexes of quinoline-2-carboxylate.
AB  - The title complexes, trans-diaquabis(quinoline-2-carboxylato
      kappa(2)N,O)cobalt(II)-water-methanol (1/2/2),
      [Co(C(10)H(6)NO(2))(2)(H(2)O)(2)].2CH(4)O.2H(2)O, and trans-diaquabis(quinoline-2
      carboxylato-kappa(2)N,O)nickel(II)-water-methanol (1/2/2),
      [Ni(C(10)H(6)NO(2))(2)(H(2)O)(2)].2CH(4)O.2H(2)O, are isomorphous and contain
      Co(II) and Ni(II) ions at centers of inversion. Both complexes have the same
      distorted octahedral coordination geometry, and each metal ion is coordinated by
      two quinoline N atoms, two carboxylate O atoms and two water O atoms. The
      quinoline-2-carboxylate ligands lie in trans positions with respect to one
      another, forming the equatorial plane, with the two water ligands occupying the
      axial positions. The complex molecules are linked together by hydrogen bonding
      involving a series of ring patterns which include the uncoordinated water and
      methanol molecules.

PMID- 12794331
TI  - An alkoxide cluster with 18 Li+ ions encapsulating two borate anions,
      [((t)BuO)12Li18(BO3)2].
AB  - The title compound, bis(borato)dodeca(tert-butoxo)octadecalithium,
      [Li(18)(BO(3))(2)(C(4)H(9)O)(12)], is formulated conveniently as
      [(((t)BuOLi)(3)(Li(3)BO(3)))(2)((t)BuOLi)(6)]. A central 12-membered ring and two
      outer six-membered rings are formed by alternating Li(+) cations and alkoxide O
      atoms. Sandwiched between the central ring and each of the outer rings is a
      planar array of three further Li(+) cations surrounding a [BO(3)](3-) anion.
      Thus, the molecule consists of a cationic [Li(18)(O(t)Bu)(12)](6+) cage
      encapsulating two borate anions. This compound is the first example of a
      structurally characterized polynuclear lithium borate, and a rare case of a
      lithium alkoxide cage with nuclearity greater than eight. All the alkoxide
      ligands are triply bridging, and the lithium ions have trigonal-planar, trigonal
      pyramidal and fourfold coordination, all with major distortions from regular
      coordination geometry.

PMID- 12794332
TI  - Bis[mu-1,2-bis(2-pyridyl)ethyne-kappa(2)N:N']bis[aquadinitratocadmium(II)].
AB  - Two twisted 1,2-bis(2-pyridyl)ethyne ligands bridge two Cd(2+) centers in the
      C(2)-symmetric title complex, [Cd(2)(NO(3))(4)(mu-C(12)H(8)N(2))(2)(H(2)O)(2)].
      The bridging ligands arch across one another creating a 'zigzag loop' molecular
      geometry. Two nitrate ions and a water molecule complete the irregular seven
      coordinate Cd-atom environment. The dihedral angles between the equivalent
      pyridyl ring planes of the two independent ligands are 67.2 (1) degrees. O(water)
      H.O(nitrate) hydrogen bonding creates two-dimensional layers parallel to the ab
      plane.

PMID- 12794333
TI  - Two isomorphous complexes: dichloro[phthalocyaninato(2-)]tin(IV) and
      dichloro[phthalocyaninato(2-)]germanium(IV).
AB  - Isomorphous triclinic forms of dichloro[phthalocyaninato(2-)]tin(IV),
      [Sn(C(32)H(16)N(8))Cl(2)], and dichloro[phthalocyaninato(2-)]germanium(IV),
      [Sn(C(32)H(16)N(8))Cl(2)], and a monoclinic form of the latter have been obtained
      from the reaction of pure tin and germanium powder, respectively, with
      phthalonitrile under a stream of ICl vapour. All three crystal structures consist
      of centrosymmetric [SnPcCl(2)] and [GePcCl(2)] [Pc is phthalocyaninate(2-)]
      molecules, which are separated but interacting. In the triclinic forms (Sn and
      Ge), the Pc macrocycles are not staggered but slipped, and in the monoclinic form
      (Ge), the molecules are additionally inclined. In both cases, the central Sn or
      Ge atom is six-coordinated by the four isoindole N atoms of the Pc macrocyclic
      ligand and by two Cl atoms (located trans) into a tetragonal-bipyramidal
      structure. The arrangement of [SnPcCl(2)] and [GePcCl(2)] molecules in the
      crystal structure is determined mainly by intermolecular C-H.Cl, pi-pi and van
      der Waals interactions.

PMID- 12794334
TI  - Bis[N,N'-diisopropyl-N-(trimethylsilyl)benzamidinium] di-mu-chloro
      bis[tetrachlorozirconate(IV)] dichloromethane disolvate.
AB  - The structure of the salt of the di-mu-chloro-bis[tetrachlorozirconate(IV)] anion
      and the N,N'-isopropyl-N-(trimethylsilyl)benzamidinium cation,
      (C(16)H(29)N(2)Si)(2)[Zr(2)Cl(10)].2CH(2)Cl(2), is reported. The anion lies about
      an inversion centre and shows a substantially octahedral coordination around Zr,
      while the structure of the cation is unequivocally assigned as that of a
      benzamidinium ion.

PMID- 12794335
TI  - Bis(cyanoguanidine)silver(I) nitrate-cyanoguanidine (1/1).
AB  - In the title compound, [Ag(C(2)H(4)N(4))(2)](NO(3)).C(2)H(4)N(4), the Ag atom is
      surrounded by three cyanoguanidine (cnge) molecules. Two monodentate cnge
      molecules form strong covalent Ag-N bonds of 2.210 (7) and 2.266 (6) A through
      their nitrile N atoms. The third cnge molecule is located in a vacant crystal
      site and is only weakly coordinated to the Ag atom as a solvate molecule. Inter-
      and intramolecular hydrogen bonds play an important role in the crystal packing.

PMID- 12794336
TI  - A bis(acetylacetonato)uranium(IV) complex of the Schiff base N,N'-bis(3
      hydroxysalicylidene)-2-methyl-1,2-propanediamine.
AB  - The title complex, bis(acetylacetonato-kappa(2)O,O')[N,N'-bis(3-hydroxy-2
      oxidobenzaldimino)-2-methyl-1,2-propanediamine-kappa(4)N,O,O',N']uranium(IV)
      tetrahydrofuran solvate, [U(C(18)H(18)N(2)O(4))(C(5)H(7)O(2))(2)].C(4)H(8)O, is a
      rare example of a uranium(IV) complex with a compartmental Schiff base. The U
      atom is located in the N(2)O(2) inner site of the hexadentate N,N'-bis(3-hydroxy
      2-oxidobenzaldimino)-2-methyl-1,2-propanediamine group and is bound also to the
      two O atoms of both acetylacetonate moieties, which results in a dodecahedral
      coordination environment. Centrosymmetric dimers are formed through
      intermolecular hydrogen bonds that link the terminal uncoordinated hydroxy groups
      to one another and to the O atoms of the acetylacetonate ligands.

PMID- 12794337
TI  - Low-dimensional compounds containing cyano groups. VI. A unique two- and one
      dimensional structure in amminebis(1,4
      diaminobutane)tetrakis[dicyanoargentato(I)]dicopper(II) dihydrate.
AB  - The title compound, [Cu(2)(C(4)H(12)N(2))(2)(Ag(CN)(2))(4)(NH(3))].2H(2)O or
      [Ag(4)Cu(2)(CN)(8)(C(4)H(12)N(2))(2)(NH(3))].2H(2)O, contains two
      crystallographically different Cu(II) atoms lying on twofold axes. The first Cu
      atom is hexacoordinated in the form of an elongated tetragonal bipyramid and is
      part of a plane in which Cu atoms are connected by two bridging diaminobutane
      molecules [Cu-N = 2.033 (4) A] and two dicyanoargentate anions [Cu-N = 2.622 (6)
      A]. The ammine ligand stands perpendicular to this plane [Cu-N = 2.011 (6) A] in
      a trans position to it. Another [Ag(CN)(2)](-) anion connects the hexacoordinated
      Cu atom [Cu-N = 1.997 (8) A] with the second Cu atom [Cu-N = 2.026 (7) A], which
      is pentacoordinated in the form of a slightly distorted trigonal bipyramid by two
      monodentate dicyanoargetate anions [Cu-N = 2.040 (5) A]. The axial positions are
      occupied by two bridging diaminobutane molecules [Cu-N = 2.011 (4) A] that
      connect the Cu atoms into chains parallel to the above plane. The water molecules
      remain uncoordinated and thus a unique combination of two- and one-dimensional
      structures is formed.

PMID- 12794338
TI  - Low-dimensional compounds containing cyano groups. VII. (Dicyanamido
      kappaN1)bis(1,10-phenanthroline-kappa2N,N')copper(II) trifluoromethanesulfonate.
AB  - The title compound, [Cu(C(2)N(3))(C(12)H(8)N(2))(2)](CF(3)SO(3)), is formed by
      discrete [Cu(phen)(2)(N(CN)(2)))](+) complex cations (phen is 1,10
      phenanthroline) and uncoordinated CF(3)SO(3)(-) anions. The Cu centre is five
      coordinated in the form of a distorted trigonal bipyramid to two phen molecules
      and one dicyanamide ligand, which is coordinated through one nitrile N atom in
      the equatorial plane at a distance of 1.990 (2) A. The two axial Cu-N distances
      are similar (mean 1.993 A) and are substantially shorter than the two equatorial
      Cu-N bonds (mean 2.125 A).

PMID- 12794339
TI  - Barium bis[6-amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dionate] trihydrate:
      coordination polymer chains linked by hydrogen bonds.
AB  - The title complex, catena-poly[[triaquabarium(II)]-di-mu-6-amino-3-methyl-5
      nitrosopyrimidine-2,4(1H,3H)-dionato], [Ba(C(5)H(5)N(4)O(3))(2)(H(2)O)(3)](n),
      forms a coordination polymer chain in which the two distinct anions use different
      ligating atoms to bridge pairs of cations. Adjacent pairs of cations are also
      linked by pairs of bridging water molecules. The chains are linked into a single
      three-dimensional framework by an extensive series of hydrogen bonds.

PMID- 12794340
TI  - (2RS)-5,6:7,8-Dibenzobicyclo[2.2.2]octan-2-ol.
AB  - The racemic form of the title secondary monoalcohol, C(16)H(14)O, forms crystals
      in which the molecules are linked into chains by hydrogen bonding. The chain
      architecture is unusual; adjacent molecules are related pseudosymmetrically, by
      either a pseudo-diad or a pseudo-glide plane, while alternate molecules are
      related exactly by a crystallographic glide plane.

PMID- 12794341
TI  - Hydrogen bonding in N,N'-bis[(1S)-2-azido-1-(2-methylpropyl)ethyl]oxalamide:
      twofold symmetry of R(2)(2)(10) hydrogen-bonded dimers connected into an alpha
      network.
AB  - The title compound, C(14)H(26)N(8)O(2), belongs to a class of retropeptides with
      an oxalamide unit (-NH-CO-CO-NH-), and is a precursor for the synthesis of an
      amine-terminal gelator. The compound is a good synthon for one-dimensional
      hydrogen bonding. The crystal structure reveals a hydrogen-bonded cyclic dimer
      with unusual twofold rotation symmetry.

PMID- 12794342
TI  - Two members of the bisphosphonate class of drugs: a zwitterion and a molecular
      compound.
AB  - The compounds studied in this paper, viz. (1-ammonio-1
      phosphonopropyl)phosphonate, C(3)H(11)NO(6)P(2), (I), and 1
      (acetylamino)propylidene-1,1-bisphosphonic acid dihydrate,
      C(5)H(13)NO(7)P(2).2H(2)O, (II), are members of a commonly used family of
      therapeutic agents. Compound (I) is an inner salt with separated negative (on the
      ionized PO(3) group) and positive (on the tetrahedral N atom) charges, while (II)
      possesses neutral phosphonyl groups and one amide N atom. Both structures have a
      C-C-C-N backbone, which has comparable geometric parameters in (I) and (II); the
      main difference was found in one of the N-C-P bond angles, which is lengthened in
      (II) because of an intramolecular O(PO(3))-H.O(C=O) interaction. The hydrogen
      bonding scheme in the crystal of (I) includes all possible donor atoms, namely
      all the H atoms of the ammonium group and the phosphonic acid functions. As a
      result of these interactions, the zwitterions are organized into a plane running
      along the crystallographic x axis. In (II), the intermolecular interactions
      include all possible donor atoms, except for the N atom; the packing differs from
      that of (I) in that the molecules are arranged in a chain running parallel to the
      x axis. In the chains, the molecules form head-to-head dimers, while the
      crystallization water molecules contribute to the intra- and interchain cohesion.

PMID- 12794343
TI  - 3,6-Dichloro-4-[2-(4-thiamorpholino)ethanesulfanyl]pyridazine and 3,6-bis(pyrazol
      1-yl)-4-[2-(4-thiamorpholino)ethanesulfanyl]pyridazine.
AB  - The trans-trans conformations adopted by the derivatized bis(bidentate) chelating
      N(4)-donor ligand 3,6-bis(pyrazol-1-yl)-4-[2-(4
      thiamorpholino)ethanesulfanyl]pyridazine, C(16)H(19)N(7)S(2), and an intermediate
      in its formation, 3,6-dichloro-4-[2-(4-thiamorpholino)ethanesulfanyl]pyridazine,
      C(10)H(13)Cl(2)N(3)S(2), contrast with the cis-cis conformation found previously
      for 3,6-bis(thiophen-2-yl)pyridazine [Ackers, Blake, Hill & Hubberstey (2002).
      Acta Cryst. C58, o640-o641], which places all four heteroatoms on the same side
      of the molecule.

PMID- 12794344
TI  - Derivatives of 4-(2-hydroxylphenyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepine.
AB  - In the structures of 2-(4-chlorophenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1,5
      benzothiazepine, C(21)H(16)ClNOS, 4-(2-hydroxyphenyl)-2-(4-tolyl)-2,3-dihydro-1,5
      benzothiazepine, C(22)H(19)NOS, and 4-(2-hydroxyphenyl)-2-(3-methoxyphenyl)-2,3
      dihydro-1,5-benzothiazepine, C(22)H(19)NO(2)S, the central seven-membered
      heterocyclic rings adopt twist-boat conformations in which the N atoms are
      involved in strong intramolecular hydrogen bonds with the hydroxyl H atoms,
      resulting in six-membered rings.

PMID- 12794345
TI  - 1-(2-Hydroxy-4-methoxyphenyl)-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one.
AB  - The title compound, C(19)H(20)O(6), crystallizes in the centrosymmetric space
      group P2(1)/c with one molecule in the asymmetric unit. The molecule is
      approximately planar and the dihedral angle between the phenyl rings is 11.0 (1)
      degrees. The H atoms of the central propenone group are trans. There is an
      intramolecular O-H.O hydrogen bond and the molecules are crosslinked by four
      intermolecular C-H.O hydrogen bonds, producing a three-dimensional network.

PMID- 12794346
TI  - 1-Acetyl-4'-ethyl-2a'-phenyl-2',2a',5',5a'-tetrahydrospiro[1H-indole-3,2'
      oxeto[5,4-b]oxazol]-2(3H)-one and 1-acetyl-4',5a'-diphenyl-2',2a',5',5a'
      tetrahydrospiro[1H-indole-3,2'-oxeto[5,4-b]oxazol]-2(3H)-one.
AB  - In the title compounds, C(21)H(18)N(2)O(4) and C(25)H(18)N(2)O(4), respectively,
      the five-membered ring of the indole system is almost planar. The oxetane and
      oxazole rings are individually planar. The orientations of the indole, oxetane,
      oxazole and phenyl moieties are conditioned by the sp(3) nature of the spiro-C
      atoms. In both compounds, the relative orientation of the indole and oxazole
      rings is opposite.

PMID- 12794347
TI  - 9,10-Diphenyl-9,10-epidioxyanthracene and 9,10-dihydro-10,10-dimethoxy-9
      phenylanthracen-9-ol.
AB  - 9,10-Diphenyl-9,10-epidioxyanthracene, C(26)H(18)O(2), (I), was accidentally used
      in a photooxygenation reaction that produced 9,10-dihydro-10,10-dimethoxy-9
      phenylanthracen-9-ol, C(22)H(20)O(3), (II). In both compounds, the phenyl rings
      are approximately orthogonal to the anthracene moiety. The conformation of the
      anthracene moiety differs as a result of substitution. Intramolecular C-H.O
      interactions in (I) form two approximately planar S(5) rings in each of the two
      crystallographically independent molecules. The packing of (I) and (II) consists
      of molecular dimers stabilized by C-H.O interactions and of molecular chains
      stabilized by O-H.O interactions, respectively.

PMID- 12794348
TI  - (E,E,E)-1,6-Bis(2,4-dichlorophenyl)hexa-1,3,5-triene.
AB  - The title molecule, C(18)H(12)Cl(4), lies about an inversion centre and the
      hexatriene chain is planar. The torsion angle of the single bond between the
      planes of the chain and the benzene ring is -8.6 (3) degrees. The dihedral angle
      between the planes defined by the chains of adjacent molecules is 50.0 (2)
      degrees. The shortest intermolecular distance between the Cl atoms is 3.514 (1)
      A. The molecules are joined through pi-pi-stacking and strong attractive Cl.Cl
      interactions.

PMID- 12794349
TI  - Dispiro[adamantane-2,2'-1',3',6',9',11',14'-hexathiacyclohexadecane-10',2"
      adamantane].
AB  - The conformational features of the title compound, C(28)H(44)S(6), are compared
      with previously reported analogous macrocycles. The type of substituent affects
      considerably the conformation of the macrocycle. A (1)H NMR titration of the
      title compound with AgBF(4) indicated the formation of the 1:1 complex, which was
      not crystallized.

PMID- 12794350
TI  - (1R,3S,6S)-6-tert-Butyl-1-hydroxymethyl-5-methoxy-6-methyl-7-oxa-4
      azaspiro[2.5]oct-4-en-8-one and dimethyl [(1S,1'R,3'S,6'S)-(6'-tert-butyl-5'
      methoxy-6'-methyl-8'-oxo-7'-oxa-4'-azaspiro[2.5]oct-4'-en-1'
      yl)hydroxymethyl]phosphonate.
AB  - The molecules of the title compounds, C(13)H(21)NO(4), (I), and C(15)H(26)NO(7)P,
      (II), are linked into chains along the c direction in (I) and along the b axis in
      (II) through O-H.O hydrogen bonds. The heteroatomic ring in (I) adopts a twist
      boat conformation, while that in (II) has a conformation intermediate between
      boat and twist-boat. The P atom has a distorted tetrahedral geometry.

PMID- 12794351
TI  - 6-(2-Hydroxybenzoyl)-5-(pyrrol-2-yl)-3H-pyrrolizine.
AB  - The title compound, 2-hydroxyphenyl 5-(pyrrol-2-yl)-3H-pyrrolizin-6-yl ketone,
      C(18)H(14)N(2)O(2), was isolated from the base-catalyzed 1:2 condensation of 2
      hydroxyacetophenone with pyrrole-2-carbaldehyde. The pyrrole N-H and
      hydroxybenzoyl O-H groups are hydrogen bonded to the benzoyl O atom. The allylic
      C=C double bond of the 3H-pyrrolizine system is located between ring positions 1
      and 2, the C atom at position 3 (adjacent to the N atom) being single bonded.

PMID- 12794352
TI  - cis,cis-Ceratospongamide N,N-dimethylacetamide hemisolvate in the presence of
      twinning.
AB  - Ceratospongamide (CS) is a potent inhibitor of secreted phospholipase A(2), and
      cis,cis and trans,trans isomers, related with respect to the two proline amide
      bonds, are known. Crystals of cis,cis-CS were grown from N,N-dimethylacetamide
      solution, giving the title compound, the cyclic ester of
      isoleucyloxazolinylphenylalanylprolylthiazolylphenylalanylproline [cyclo(-Ile-Oxz
      Phe-Pro-Thz-Phe-Pro-)] N,N-dimethylacetamide hemisolvate,
      C(41)H(49)N(7)O(6)S.0.5C(4)H(9)NO. The structure is the third example of cis,cis
      CS to be investigated and comprises twinned crystals, in which the a and b axes
      are interchanged. The ratio of co-existing twin crystals is approximately 50%.
      The peptide has a 'saddle-like' structure and is very similar to previously
      reported structures of cis,cis-CS, which implies that the structure of cis,cis-CS
      is very stable in spite of differences in crystallization conditions.

PMID- 12794353
TI  - Ammonium N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)glycinate
      monohydrate forms hydrogen-bonded bilayers.
AB  - In the title compound, NH(4)(+).C(7)H(8)N(5)O(4)(-).H(2)O, the independent
      components are linked into bilayers by an extensive series of two-centre N-H.O
      hydrogen bonds [H.O = 1.85-1.96 A, N.O = 2.776 (2)-2.840 (2) A and N-H.O = 149
      172 degrees ], and by asymmetric three-centre N-H.(O)(2), O-H.(N,O) and O
      H.(O)(2) hydrogen bonds.

PMID- 12794354
TI  - meso-5,5,7,12,12,14-Hexamethyl-4,11-diaza-1,8-diazoniacyclotetradecane (S)
      malate(2-) methanol disolvate: a chain of rings generated by two pairs of N-H.O
      hydrogen bonds.
AB  - The title compound is a methanol-solvated salt, C(16)H(38)N(4)(2+).C(4)H(4)O(5)(2
      ).2CH(3)OH, in which the ionic components are linked into chains by two pairs of
      N-H.O hydrogen bonds [H.O = 1.78-2.21 A, N.O = 2.702 (14)-3.094 (8) A and N-H.O =
      160-179 degrees ]. The methanol molecules are pendent from the chain and are
      linked to it by O-H.O hydrogen bonds [H.O = 1.86 and 1.89 A, O.O = 2.691 (9) and
      2.708 (16) A, and O-H.O = 168 and 165 degrees ].

PMID- 12794356
TI  - Hydrogen-bonded dimers of 1,8,10-trihydroxy-10-(prop-2-enyl)anthracen-9(10H)-one:
      S(6), R(2)(1)(10) and R(2)(2)(14) motifs.
AB  - The central ring of the anthrone system in the title compound, C(17)H(14)O(4),
      has a shallow envelope conformation, and each of the two outer rings is inclined
      at an angle of 17.41 (3) degrees. In the solid state, the molecules exist as
      centrosymmetrically related O-H.O hydrogen-bonded dimers. Two intramolecular O
      H.O hydrogen bonds, involving the central carbonyl O atom and having a graph-set
      motif of S(6), are observed. These intramolecular interactions lead co
      operatively to an O-H.O.H-O pattern that has a binary graph-set motif of
      R(2)(1)(10).

PMID- 12794355
TI  - Two bis(ammonium) 1,5-naphthalenedisulfonate salts.
AB  - The title compounds, bis(ammonium) naphthalene-1,5-disulfonate,
      2NH(4)(+).C(10)H(6)O(6)S(2)(2-), and bis[1-(hydroxymethyl)-3,5,7-triaza-1
      azoniatricyclo[3.3.1.1(3,7)]decane] 1,5-naphthalenedisulfonate,
      2C(7)H(15)N(4)O(+).C(10)H(6)O(6)S(2)(2-), were prepared from the acid-promoted
      reaction of hexamethylenetetramine. In both structures, the disulfonate anion is
      positioned on an inversion center, with each sulfonate group contributing to the
      supramolecular assemblies via hydrogen bonds. The ammonium cations are linked to
      sulfonate groups by four distinct N(+)-H.(-)O-S contacts [N.O = 2.846 (2)-2.898
      (2) A and N-H.O = 160 (2)-175 (2) degrees ], whereas the 1-(hydroxymethyl)-3,5,7
      triaza-1-azoniatricyclo[3.3.1.1(3,7)]decane cations form one O-H.(-)O-S [O.O =
      2.628 (2) A and O-H.O = 176 degrees ] and three C-H.(-)O-S [C.O = 3.359 (2)-3.380
      (2) A and C-H.O = 148-155 degrees ] interactions to neighboring sulfonate groups.

PMID- 12794357
TI  - 2-Allenyl-2H-benzotriazole.
AB  - In the title compound, C(9)H(7)N(3), the allenyl form of the side chain (
      CH=C=CH(2)) is found in preference to the propargyl form (-CH(2)-C[triple
      bond]CH). The bond distances between the C atoms in the side chain are 1.303 (3)
      and 1.289 (3) A.

PMID- 12794358
TI  - 6-Amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione forms a three-dimensional
      hydrogen-bonded framework structure.
AB  - Molecules of the title compound, C(5)H(6)N(4)O(3), are linked into a single three
      dimensional framework by a two-centre N-H.O hydrogen bond [H.O = 1.92 A, N.O =
      2.785 (2) A and N-H.O = 168 degrees ], a two-centre N-H.H hydrogen bond [H.N =
      2.19 A, N.N = 3.017 (2) A and N-H.N = 157 degrees ] and the intermolecular
      component of an effectively planar three-centre N-H.(O)(2) hydrogen bond [H.O =
      2.03 and 2.31 A, N.O = 2.645 (2) and 2.957 (2) A, N-H.O = 126 and 130 degrees,
      and O.H.O = 101 degrees ].

PMID- 12794359
TI  - 1,4,7-Tris(2-cyanoethyl)-4,7-triaza-1-azoniacyclononane perchlorate.
AB  - There are three independent molecules in the asymmetric unit of the title
      compound, C(15)H(25)N(6)(+).ClO(4)(-). The cations are linked to form an
      R(4)(4)(30) ring with two arms and are then linked into columns in the [010]
      direction by C(11) chains formed via C-H.N hydrogen bonds.

PMID- 12794360
TI  - t-3-Isopropyl-1-methyl-r-2,c-6-diphenylpiperidin-4-one thiosemicarbazone.
AB  - The piperidine ring in the title compound, C(22)H(28)N(4)S, exhibits a chair
      conformation. The thiosemicarbazone moiety adopts an extended conformation, and
      the planar phenyl rings are oriented equatorially with respect to the piperidine
      ring. Two intermolecular hydrogen bonds involving the S atom form molecular
      pairs, and the crystal structure is stabilized by weak C-H.pi interactions in
      addition to van der Waals forces.

PMID- 12794361
TI  - Bis(melaminium) DL-malate tetrahydrate.
AB  - The crystal structure of the title melaminium salt, bis(2,4,6-triamino-1,3,5
      triazin-1-ium) DL-malate tetrahydrate, 2C(3)H(7)N(6)(+).C(4)H(4)O(5)(2-).4H(2)O,
      consists of singly protonated melaminium residues, DL-malate dianions and water
      molecules. The melaminium residues are connected into chains by four N-H.N
      hydrogen bonds, and these chains form a stacking structure along the c axis. The
      DL-malate dianions form hydrogen-bonded chains and, together with hydrogen-bonded
      water molecules, form a layer parallel to the (100) plane. The conformation of
      the malate ion is compared with an ab initio molecular-orbital calculation. The
      oppositely charged moieties, i.e. the stacks of melaminium chains and hydrogen
      bonded DL-malate anions and water molecules, form a three-dimensional polymeric
      structure, in which N-H.O hydrogen bonds stabilize the stacking.

PMID- 12794362
TI  - 3-[2,6-Bis(diethylcarbamoyl)pyridin-4-yl]-N-(tert-butoxycarbonyl)alanine methyl
      ester: a chiral tridentate ligand that causes a diastereomeric excess of its
      lanthanide complexes in solution.
AB  - L(4), or 3-[2,6-bis(diethylcarbamoyl)pyridin-4-yl]-N-(tert-butoxycarbonyl)alanine
      methyl ester, C(24)H(38)N(4)O(6), crystallizes in neat [010] laths stabilized by
      abundant intra- and intermolecular hydrogen bonds. The strongest of these form
      [010] chains of molecules, thus rationalizing the fastest growth direction, while
      the slowest direction coincides with the normal to the (110) layers, which are
      linked by very weak hydrogen bonds. There exist two independent molecules, the
      distances and bond angles of which differ in a random manner only. The torsion
      and dihedral angles, however, differ so as to achieve optimal packing. The
      influence of the chiral group in the 4-position of the pyridine ring on the
      helical wrapping and on the ensuing diastereomeric induction is briefly
      discussed.

PMID- 12794363
TI  - [Anticitrulline antibodies - new marker in rheumatoid arthritis diagnostics].
AB  - The overview provides the knowledge about rheumatoid factor isotypes and their
      significance in the case of rheumatoid arthritis. New immunological methods have
      been introduced in the last decade proving their validity in seronegative
      rheumatoid arthritis. Antikeratin and anticitrulline antibodies were found to be
      useful diagnostic tools for seronegative and early rheumatoid arthritis. The
      methods perform well for scientific needs as well as in daily clinical practice.

PMID- 12794364
TI  - [Erythema nodosum association with malignant lymphoma].
AB  - Erythema nodosum is the most frequent clinicopathological variant of the
      panniculitides. The disorder is a cutaneous reaction consisting of inflammatory
      nodular lesions, usually located on the lower extremities. It may be associated
      with a wide variety of diseases, infections, sarcoidosis, rheumatologic diseases,
      inflammatory bowel diseases, medications and malignancies. Relationship between
      erythema nodosum and malignant lymphoma is described in the article. A review of
      the literature suggest that the diagnosis of Hodgkin's and non-Hodgkin's disease
      should be considered in patients with unexplained erythema nodosum.

PMID- 12794365
TI  - [Paraneoplastic rheumatic syndromes].
AB  - Fifteen percent of patients with malignancy are diagnosed endocrinal,
      hematological, rheumatic or neuromuscular paraneoplastic syndromes. They are more
      common in males than in females. Rheumatic paraneoplastic syndromes are quite
      rare. Differences in clinical features, course and outcomes of primary rheumatic
      disease and paraneoplastic rheumatic syndromes are reviewed. Attention is paid to
      the need to differentiate paraneoplastic syndromes and real rheumatic disease and
      the ways to do it. It is generally held that an extensive search for occult
      malignancy in most rheumatic syndromes is not recommended unless accompanied by
      specific findings of malignancy.

PMID- 12794366
TI  - [Influence of glucocorticoids on bone mineral density in rheumatoid arthritis and
      seronegative spondyloarthropathies].
AB  - Glucocorticoids are commonly used for treatment of rheumatoid arthritis and
      seronegative spondyloarthropathies. The aim of this study was to investigate the
      influence of the glucocorticoids for the bone mineral density of patients with
      chronic autoimmune arthritides, to evaluate the importance of the duration and
      dosage of the treatment, and to compare with well-known risk factors for
      osteoporosis: age and sex of patients, duration of menopause, length of the
      arthritis-related functional insufficiency. One-hundred-eighty-eight rheumatoid
      arthritis and 97 seronegative spondyloarthropathies patients were investigated.
      Bone mineral density was examined by the method of dual energy x-ray
      absorptiometry (Hologic QDR 4500 W) in the vertebral bodies of the lumbar spine
      and the hip. Relative risk of glucocorticoids for development of osteopenia and
      osteoporosis was moderate, less significant than the impact of patient's age.
      Negative influence of glucocorticoids on the bone mineral density was related
      with cumulative dose and duration of the treatment. In rheumatoid arthritis
      patients it was more significant, than in cases of seronegative
      spondyloarthropathies. Diminishing of the bone mineral density was more important
      in the lumbar spine, the changes in hip mineralization were less expressed in
      both diseases.

PMID- 12794367
TI  - [Antiphospholipid syndrome in patients with systemic connective tissue diseases].
AB  - The present study evaluates the incidence of antiphospholipid antibody syndrome
      (APS) in systemic rheumatic diseases patients with anticardiolipin antibodies.
      Clinical presentations of systemic rheumatic diseases in patients with or without
      APS are examined as well. The data from 242 consecutive patients suffering from
      rheumatoid arthritis (158 pts), systemic erythematoid lupus (53 pts), or systemic
      sclerosis (31 pts) are studied. Enzyme immunoassay test for IgG-anticardiolipin
      antibodies was performed for all patients. The IgG-anticardiolipin antibodies
      were found in 38 (15.7%) patients. There were 16 (30.2%) patients in erythematoid
      lupus group, 9 (29%) patients in systemic sclerosis group, and 13 (8.2%) patients
      in rheumatoid arthritis group. The diagnosis of secondary APS according to
      classificational criteria (1998) was confirmed in 14 (36.8%) from 38 seropositive
      patients: ten patients (62.5%) in lupus group, 2 (22.2%) patients in systemic
      sclerosis group, and 2 (15.4%) patients in rheumatoid arthritis group were found
      as APS patients. The majority of these patients were female (92.9%). These
      patients were younger as compared with systemic rheumatic diseases patients
      without APS (p=0.005). There was no significant difference found between APS
      patients and patients without APS in respect to neither duration of primary
      disease, nor disease activity, nor course of the disease. There were
      significantly more cases of fibrotic heart valves (p=0.028), and thrombocytopenia
      (p=0.002), and livedo reticularis (p=0.058) in APS group.

PMID- 12794368
TI  - [Mycoplasmal infection in patients with reactive arthritis and seronegative
      spondyloarthropaties].
AB  - After investigation of 150 patients with reactive arthritis and undifferentiated
      spondyloarthropathies, inflammation signs of urogenital tract (uretritis in men
      and endocervicitis in women) were found in about 2/3 of patients. In those
      patients with reactive arthritis and undifferentiated spondyloarthropathies
      Ureaplazma urealyticum was found in more than 1/4 of patients, Mycoplasma hominis
      - in 1/10 of patients, and both microbes appeared in 1/10 of patients.
      Micoplasmal infection occurred in equal frequency in patients with reactive
      arthritis and undifferentiated spondyloarthropathies with a tendency to appear
      more in women than in men.

PMID- 12794369
TI  - [Changes of bone mineral density in rheumatoid arthritis].
AB  - The aim of the study was to evaluate changes of bone mineral density in
      rheumatoid arthritis (RA) patients in one-year period and to establish the
      possible relation with the clinical and laboratory symptoms of inflammation and
      radiological signs of structural damage of the joints. Forty-one RA patient was
      investigated. Clinical activity of rheumatoid arthritis was assessed by the
      duration of morning stiffness, counts of tender and swollen joints, and general
      evaluation of the disease activity by the patient and investigator. Erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) were used as laboratory
      markers of activity of inflammation. X-ray progression was evaluated by the
      appearance of new erosions and worsening of the joint spaces on the hands X-ray.
      Bone mineral density was measured by DEXA method (QDR 4500W Elite Hologic, USA)
      in the 1-4 lumbar vertebral bodies, and in the proximal part of the hip. It was
      established that systemic bone mineral density lossin all investigated locations
      was characteristic for active rheumatoid arthritis. Bone mineral density
      diminishing in the hip was in close correlation with the and symptoms of disease
      activity and radiological progression. This correlation was not characteristic
      for the lumbar vertebral bodies. Above-mentioned clinical, laboratory and
      radiological features of the disease had minimal influence on bone mineral
      density for the patients with long-standing rheumatoid arthritis.

PMID- 12794370
TI  - [Osteochondral transplantation (mosaicplasty) in the treatment of knee joint
      cartilage defects].
AB  - Between 1998 and 2001 thirty-five patients underwent osteochondral
      transplantation (mosaicplasty) and 35 patients (controls) - microfracture
      procedure for osteochondral or chondral knee joint pathology treatment. Average
      age of patients was 24.74+/-7.20 years. Patients were evaluated through
      International Cartilage Repair Society (ICRS) and modified Hospital for special
      Surgery (HSS) scales, arthroscopically, histologically, with MRI and x-rays.
      Modified HSS and ICRS evaluation showed statistically significantly better
      results in the mosaicplasty group 12 months post operation (p=0.005). Last follow
      up showed deterioration in microfracture group (p=0.0005).

PMID- 12794371
TI  - [Henoch-Schonlein purpura - one of the most common types of systemic vasculitis
      in childhood].
AB  - The aim of our study was to estimate etiology, most common clinical findings, the
      course and peculiarities of treatment in children to whom Henoch-Schonlein
      purpura was diagnosed during 1996-2002 at Clinic of Children's Diseases of Kaunas
      University of Medicine Hospital. METHODS: The Henoch-Schonlein purpura diagnosis
      was based on the association of non-trombocytopenic purpura, arthritis and
      abdominal pain in 45 children, mostly at preschool age. Routine laboratory blood
      tests usually were normal. Serum level of imunoglobulin A (Ig A), complement 3, 4
      (C(3), C(4)), antineutrophil cytoplasm antibodies were measured for some
      patients. Urinary analyses were performed for all patients in order to assess
      nephritis. RESULTS: In 1/3 (33.3%) of children Henoch-Schonlein purpura was
      preceded by an upper respiratory tract infection. The most common clinical signs
      were: non-trombocytopenic purpura -100%, subcutaneous edema - 53%, arthritis of
      large joints - 64%, gastrointestinal symptoms (pain, diarrhea with bleeding) -
      37.5%. The incidence of renal involvement was 13.3%, but usually not at the onset
      of the disease. Relapses were often, and they had tendency to repeat in 1-2 week
      periods. Late relapses were absent. Treatment of Henoch-Schonlein purpura was
      symptomic. Nonsteroidal anti-inflammatory drugs which are helpful in joint pain,
      were prescribed for 33.3% patients. Steroids which reduce abdominal pain, melena,
      massive hemorrhage, nephritic symptoms, were given for 28.8% patients.
      CONCLUSIONS: Non-trombocytopenic purpura, arthritis and colic abdominal pain,
      classic triad of Henoch-Schonlein purpura that occurs in early stage of the
      disease, were most common. Renal involvement had tendency occur later.
      Nonsteroidal anti-inflammatory drugs were prescribed for patients with arthritis;
      prednisone reduced gastrointestinal, nephritic symptoms. Relapses were often.

PMID- 12794373
TI  - [Rheumatoid arthritis: the usefulness of power Doppler sonography].
AB  - The purpose of this study was to investigate the intra-articular vascularization
      of the synovial pannus of patients with rheumatoid arthritis with power Doppler
      sonography and to correlate these findings with clinical findings and laboratory
      measures of disease activity. Seventy-four different joints of 23 patients with
      diagnosis of rheumatoid arthritis were studied. Clinical and functional
      assessment (number of swollen joints, visual analogue scale) and laboratory
      evaluation were made for all patients. Disease activity was evaluated using the
      disease activity score (DAS28) for each patient. The power Doppler sonography
      vascularity of the synovial membrane was classified semiquantatively. The strong
      correlation was found between qualitative power Doppler sonography results with
      joints with clinically active arthritis (Spearman's correlation coefficient was
      0.67, p=0.0001). The power Doppler sonography was weakly correlated with disease
      activity score. No correlation was found with age, disease duration, and other
      laboratory and clinical variables. Power Doppler sonography may be a valuable
      tool to detect synovial vascularity and to assist clinicians in distinguishing
      between inflammatory and non-inflammatory pannus.

PMID- 12794372
TI  - [Correlation of power Doppler sonography with vascularity of the synovial
      tissue].
AB  - The purpose of this study was to investigate the intra-articular vascularization
      of the synovium with power Doppler sonography and correlate these findings with
      histopathologic al findings of synovial vascularity. Before arthroplasty or
      arthroscopy with synovectomy the knee joints of 20 patients with osteoarthritis
      or rheumatoid arthritis were examined with power Doppler sonography. Vascularity
      of the synovial membrane was classified semi quantitatively. The degree of the
      synovial vascularity was graded quantitatively using histological method. The
      strong correlation was found between qualitative power Doppler sonography results
      with histological findings of vascularity (Spearman's correlation coefficient was
      0.85, p=0.0005). Power Doppler sonography may be a valuable tool to detect
      synovial vascularity and to assist clinicians in distinguishing between
      inflammatory and non-inflammatory synovium.

PMID- 12794374
TI  - [A rare case of differential diagnosis of myopathy].
AB  - Relationship among thyroid dysfunction and musculoskeletal symptoms has been
      known for years. Autoimmunic thyroiditis is the most common cause of
      hypothyrosis. A patient who suffered from myopathy secondary to autoimmunic
      thyroiditis and hypothyrosis is described in this article. Attention has been
      drawn to proximal muscle weakness and general fatigue which is common in such
      cases. Significant elevation of muscle enzymes is typical. Usually no specific
      signs can be found on muscle biopsy. Much efforts should be put to distinguish
      myopathy secondary to hypothyrosis from polymyalgia rheumatica, polymyositis or
      myopathies caused by other diseases. Similar data of literature are reviewed in
      the article.

PMID- 12794375
TI  - [Wegener's granulomatosis in childhood].
AB  - Our aim is to elucidate the rare case of Wegener granulomatosis in childhood: its
      clinical symptoms, treatment, complications and outcome. We present clinical case
      of 12-year-old boy with affection of airways, kidneys, skin, joints and eyes.
      Diagnosis was confirmed on the basis of clinical picture, laboratory findings and
      ultrasound, x-ray, computed tomography, magnetic resonance imaging and biopsies
      of skin, nasal mucosa, renal tissues. We found four of five positive modified
      American College of Rheumatology diagnostic criteria. Conventional treatment with
      corticosteroids and cyclophosphamide eliminated renal symptoms, but the damage of
      the upper and central airways increased with development of subglottic stenosis.
      This complication was treated by urgent tracheostomy. Remission of disease was
      achieved with maximal doses of corticosteroids ant cyclophosphamide during 13
      months from of symptoms onset. Peculiarities of our case were early onset, rapid
      development of life threatening symptoms, treatment with large doses of drugs and
      urgent surgery. Aforementioned active treatment did not prevent complications -
      steroid side effects, infections, bone fracture and subglottic stenosis.

PMID- 12794376
TI  - [Bone mineral density in healthy Lithuanian women].
AB  - OBJECTIVE: The purposes of this investigation were to determine spine and femoral
      bone mineral density for a representative sample of healthy women of Lithuanian
      descent and to compare these results with US/European reference data. METHODS: We
      randomly selected 1200 women aged 20-79 years from Lithuanian population
      registers. Densitometry of the lumbar spine and left proximal femur was
      determined by a LUNAR DPX-IQ system (Lunar corp., Madison, WI). The general
      exclusion criteria for the construction of representative samples of Lithuanian
      women included early menopause and diseases, use of drugs and toxic habits such
      as smoking and alcoholism, known to affect bone and mineral metabolism. RESULTS:
      Eight-hundred-seven women completed the study. The bone mineral density results
      were grouped into 10-year age cohorts. A comparison between the Lithuanian and
      Caucasian data, using the two-tailed t-test, showed that there was no
      statistically significant difference between them for all age groups at the
      P<0.05 level. The Lithuanian women show the expected gradual reduction of bone
      mineral density with age, after peaking at 20-39. The bone mineral density of
      Lithuanian women tends to mirror rates of loss established for US/European
      subjects. CONCLUSION: Our bone mineral density measurements for healthy
      Lithuanian females are not significantly different from the normative Caucasian
      female reference data both in terms of average values and degree of spread.

PMID- 12794377
TI  - [Vilnius rheumatoid arthritis registry].
AB  - OBJECTIVE: To analyze the disease characteristics, health status, working
      ability, treatment specificities of rheumatoid arthritis (RA) patients referred
      to Vilnius rheumatoid arthritis register and to compare the data with those
      reported from other countries rheumatoid arthritis registers. MATERIALS AND
      METHODS: Rheumatoid arthritis patients' characteristics were analysed using the
      data of the Vilnius Rheumatoid arthritis register established in the end of 1998
      and comprising 1018 rheumatoid arthritis patients from 486506 adult Vilnius
      citizens. The data were compared to those reported from Oslo Rheumatoid arthritis
      register, Norfolk Arthritis Register and German rheumatological database.
      RESULTS: Of all patients, 83.7% were women on the average 60.4 years old. The
      average disease duration was 12.2 years. Of the whole group of patients, 24% were
      working people, as many as 58.2% were disabled and most often had the second
      third functional class. Non-steroidal anti-inflammatory drugs were taken
      practically by all rheumatoid arthritis patients (98.3%); 74.3% of the patients
      were taking corticosteroids. The corticosteroid injections into the joints,
      mostly into the knee-joints, had been performed to 53.5% of the patients in the
      past. The treatment with disease-modifying antirheumatic drugs (DMARDs), most
      commonly sulfasalazine, was applied to 85.6% of rheumatoid arthritis patients.
      Surgery of joints was applied to 13.4% of the patients: synovectomy to 8.7%,
      prosthesis operations to 4.7%. Prosthesis operations were performed on the
      average after 16 years from the beginning of the disease. CONCLUSION: The
      majority of rheumatoid arthritis patients were elder women. As a rule, the
      treatment with DMARDs, most commonly sulfasalazine, was prescribed to the
      patients who had been ill for a short period of time. The rheumatoid arthritis
      patients in Vilnius were more often unemployed, disabled, with worse physical
      function. The demografical data of responders and non-responders were similar.

PMID- 12794378
TI  - [The problems of rehabilitation of patients with musculoskeletal and connective
      tissue diseases].
AB  - According to the data of the State Committee for Social-Medical Examination we
      analyzed general disability during 5-year period (1997-2001). Primary disability
      due to musculoskeletal and connective tissue diseases in Lithuania is in the
      second disease place in structure of disability. This article describes the
      possibilities of rehabilitation of patiens with musculoskeletal and connective
      tissue diseases.

PMID- 12794379
TI  - [Differential diagnosis of acute arthritis].
AB  - Acute arthritis can first present as a symptom of dangerous and rapidly
      progressing disease. It is quite easy to differentiate between arthritis and
      periarthritis. More problematical is correct early differential diagnosis of the
      acute arthritis. Determining whether one, several or many joints are affected can
      narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing
      provide much information and should be done at initial evaluation if possible.
      The presence or absence of fever, rash, family history of joint disease and
      exposure to infective organisms can further direct diagnostic studies and
      treatment. In general, to avoid masking clues, drug therapy should be delayed for
      mild symptoms until diagnosis is complete. This article is designed mostly for
      primary care physicians, residents and includes author's original data and review
      of recommended reading.

PMID- 12794380
TI  - The impact of depressive symptoms on patients with Alzheimer disease.

PMID- 12794381
TI  - The magnitude of dementia occurrence in the world.
AB  - In this study, the worldwide occurrence of dementia in 2000 and during the period
      1950-2050 was estimated. The calculations were based on worldwide demographics of
      the elderly and age-specific prevalence and incidence values of dementia,
      estimated from a meta-analysis. In a sensitivity analysis, different prevalence
      sources were used. The worldwide number of persons with dementia in 2000 was
      estimated at about 25 million persons. Almost half of the demented persons (46%)
      lived in Asia, 30% in Europe, and 12% in North America. Fifty-two percent lived
      in less developed regions. About 6.1% of the population 65 years of age and older
      suffered from dementia (about 0.5% of the worldwide population) and 59% were
      female. The number of new cases of dementia in 2000 was estimated to be 4.6
      million. The forecast indicated a considerable increase in the number of demented
      elderly from 25 million in the year 2000 to 63 million in 2030 (41 million in
      less developed regions) and to 114 million in 2050 (84 million in less developed
      regions). In conclusion, the majority of demented elders live in less developed
      regions, and this proportion will increase considerably in the future.

PMID- 12794382
TI  - Driving cessation in older men with dementia.
AB  - The process of driving cessation was studied in a group of older men with
      dementia. During the initial phase of the project, 53 drivers with dementia
      provided information about their driving history, driving habits, and
      expectations about driving cessation. A collateral for each patient completed a
      similar questionnaire providing corroborating information about the patient's
      driving. Collaterals were contacted 25-39 months later to gather information
      about patients' current driving habits. Twenty patients (46.5%) continued to
      drive almost 5 days per week. Twenty-three subjects (53.5%) were no longer
      driving at follow-up. The decision to stop driving was frequently abrupt and
      often made in response to a physician recommendation. Using logistic regression
      analyses, lower Mini-Mental State Examination scores (p = 0.02) and increased age
      (p = 0.02) at baseline were shown to be significant predictors of driving
      cessation. Findings indicate that an unexpected number of men with dementia
      continue to drive for several years after disease onset.

PMID- 12794383
TI  - Evaluation of the diagnosis and management of cognitive impairment in long-term
      care.
AB  - The objective was to determine the prevalence of screening for cognitive
      impairment and its effect on diagnosis and management of cognitive impairment in
      a long-term care setting, especially in comparison to depressive and behavioral
      symptoms. The study was a prospective cohort study of medical records of 60
      patients admitted to the 120 bed Veterans Administration Nursing Home in San
      Francisco. Screening was determined by documented results on the Mini-Mental
      Status Examination, Geriatric Depression Scale, and Minimum Data Set. Diagnosis
      and management were determined by review of medical records for provider
      documentation. Strategies for management were broad, including interventions such
      as pharmacological therapy, education, behavioral strategies, or caregiver
      interventions. Screening was conducted routinely for cognitive impairment (95%),
      depressive symptoms (95%), and behavioral symptoms (85%). Cognitive status was
      uncertain in 8 patients; 23 (44%) met criteria for cognitive impairment. Twelve
      (52%) had a differential diagnosis of cognitive impairment and 11 (48%) had
      evidence of strategies for management. Depressive and behavioral symptoms were
      equally or almost as common as cognitive impairment (44% and 25%, respectively),
      but evidence of a management plan was more frequently present (80% and 100%; p =
      0.002 vs. with cognitive impairment). Although depressive and behavioral symptoms
      were frequently diagnosed and interventions initiated, the diagnosis and
      management of cognitive impairment were often imprecise or absent. Further
      research is needed to identify barriers to diagnosis and management so that
      greater numbers of patients can benefit from recommended strategies.

PMID- 12794385
TI  - Reasons for seeking genetic susceptibility testing among first-degree relatives
      of people with Alzheimer disease.
AB  - Advances in genetic research have provided a basis for susceptibility testing for
      Alzheimer disease (AD). Prior surveys have examined attitudes toward genetic
      testing for AD in hypothetical scenarios, but it is unclear what reasons would
      motivate people to seek testing in real-life situations. This study presents data
      from the first randomized trial to evaluate genetic susceptibility testing for
      asymptomatic adult children of people with AD. We examined (1) reasons endorsed
      as motivations for seeking testing, (2) demographic characteristics associated
      with these reasons, and (3) how these reasons related to the eventual decision to
      pursue testing. Eligible participants were 206 adult children of people with AD
      (mean age 53 years; 72% female; 93% white), 77.7% of whom (n = 160) went on to
      seek testing. Participants endorsed numerous reasons for seeking susceptibility
      testing (mean 7.2), encompassing a range of motivations. The most commonly
      endorsed reasons were as follows: (1) to contribute to research (93.9%), (2) to
      arrange personal affairs (87.4%), and (3) the hope that effective treatment will
      be developed (86.8%). Women strongly endorsed more reasons for seeking testing
      than men (p < 0.05). The best predictor of actual pursuit of testing was strong
      endorsement of the need to prepare family members for AD (odds ratio = 3.3, p <
      0.01). Findings suggest that genetic susceptibility testing is of interest to
      individuals at risk for AD for a variety of reasons, even in the relative absence
      of available treatments.

PMID- 12794384
TI  - Evolution of depressive symptoms in Alzheimer disease: one-year follow-up.
AB  - The current longitudinal study analyzes the natural course of depressive symptoms
      in patients with Alzheimer disease (AD). The goals were to identify the clinical
      and sociodemographic variables related to depressive symptoms, to assess the
      effect of depressive symptoms on the course of cognitive and functional
      impairment and on associated neuropsychiatric disorders, and to identify which
      factors are associated with remission, persistence, and emergence of depressive
      symptoms at 12 months. A sample of 150 patients with mild or moderate severity
      was assessed at baseline and at 12 months using the neuropsychologic battery
      Cambridge Cognitive Examination. The Neuropsychiatric Inventory and Rapid
      Disability Rating Scale were administered to the caregiver. Prevalence,
      persistence, and emergence of depressive symptoms at baseline were 51%, 55%, and
      20%, respectively. Remission of depressive symptoms at 12 months leads to a
      decreased frequency of other noncognitive disorders and to a slight improvement
      in the assessment of global function. The presence of depressive symptoms does
      not affect the course of cognitive impairment at 12 months, and a psychiatric
      history of the patient and the number of depressive symptoms at baseline are risk
      factors for the emergence and persistence of depressive symptoms at 12 months.

PMID- 12794386
TI  - Lack of association between interleukin-1alpha polymorphism and Alzheimer disease
      or vascular dementia.
AB  - Recently, a C/T polymorphism in the promoter region of the interleukin 1-alpha
      (IL-1alpha) gene (position -889) was reported to be associated with Alzheimer
      disease. In this study, the polymorphism of IL-1alpha was examined in patients
      with Alzheimer disease, vascular dementia, and nondemented controls in a Chinese
      population in Taiwan. No difference was found in the IL-1alpha T allele frequency
      among the three groups. The predominant polymorphic allele ( approximately 90%)
      of IL-1alpha was the C allele. The APOE4 allele was overrepresented in the AD
      cohort. The presence of the APOE4 allele did not influence the IL-1alpha genotype
      or allele distribution. The prevalence of the IL-1alpha T allele, in particular
      the homozygous form, was lower than in whites and may account for the lack of
      association between IL-1alpha C/T polymorphism and Alzheimer disease among
      Chinese in Taiwan. The presence of the heterozygous IL-1alpha T allele cannot be
      used for distinguishing Alzheimer disease or vascular dementia from controls.

PMID- 12794387
TI  - Interchanging scores between clinical dementia rating scale and global
      deterioration scale.
AB  - Clinical Dementia Rating (CDR) scale and Global Deterioration Scale (GDS) are
      commonly used to measure the severity of dementia. However, no specific rules are
      available to convert the scores of CDR into those of GDS and vice versa. Using a
      semi-structured interview, two examiners independently rated CDR and GDS in 78
      patients with dementia and 34 controls. Regression analysis showed a curvilinear
      relationship between CDR and GDS. This curve may provide a rule to interchange
      the scores of GDS and CDR (or Sum of Boxes of CDR).

PMID- 12794388
TI  - Familial primary progressive aphasia.
AB  - Primary progressive aphasia (PPA) is a neurodegenerative disease presenting with
      isolated, progressive, language dysfunction. After at least 2 years, dementia may
      develop, but the aphasia predominates. Few families with hereditary PPA have been
      reported; some have autosomal dominance. A chromosome 17 mutation in tau exon 13
      has been found in one family, and a few have linkage to chromosome 17. However,
      early appearance of prominent memory, behavior, and motor impairments
      differentiates these patients from typical PPA. The objective was to report
      clinical features, pathology, and genetic analysis of a family with typical PPA.
      We report three siblings with the typical clinical syndrome of PPA. Each
      presented with word-finding difficulties and early anomia. Ages at onset were 60,
      61, and 65 years. Aphasia was the only symptom for at least 2 years. A
      nonaffected brother is 75 years of age. Family history review found no other
      affected relatives. Neuropathology in one patient demonstrated "dementia lacking
      distinctive histopathology" with ubiquitin-positive cortical neurons. DNA
      analysis of the proband did not detect any known mutation in tau exons 1-5, 7, or
      9-13. To our knowledge, this is the first family presenting with hereditary
      aphasia in which typical PPA occurs in all affected members.

PMID- 12794389
TI  - Combination therapy of donepezil and vitamin E in Alzheimer disease.
AB  - A retrospective chart review was performed on 130 patients from the Ohio State
      University Memory Disorders Clinic to examine the long-term effects of
      combination therapy with donepezil and vitamin E on patients with Alzheimer
      disease. Subjects were included if they met National Institute of Neurological
      and Communicative Disorders and Stroke and Alzheimer's Disease and Related
      Disorders Association criteria for probable Alzheimer disease, had taken at least
      5 mg donepezil and at least 1000 U vitamin E daily, had at least a 1-year follow
      up while continuing these medications, and had a Mini-Mental State Examination
      score of 10-24. The Mini-Mental State Examination was then recorded annually
      thereafter. These data were compared with the Consortium to Establish a Registry
      for Alzheimer's Disease database for patients collected prior to the availability
      of these treatment options. Patients declined at a significantly lower rate as
      compared with the Consortium to Establish a Registry for Alzheimer's Disease
      data. The long-term combination therapy of donepezil and vitamin E appears
      beneficial for patients with Alzheimer disease. Future prospective studies would
      be needed to compare combination treatment to vitamin E and donepezil alone.

PMID- 12794390
TI  - Inhibition of human cholinesterases by drugs used to treat Alzheimer disease.
AB  - Current approaches to the treatment of cognitive and behavioral symptoms of
      Alzheimer disease emphasize the use of cholinesterase inhibitors. The kinetic
      effects of the cholinesterase inhibitors donepezil, galantamine, metrifonate,
      physostigmine, rivastigmine, and tetrahydroaminoacridine were examined with
      respect to their action on the esterase and aryl acylamidase activities of human
      acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE). Each of
      these drugs inhibited both AChE and BuChE, but to different degrees. Inhibition
      of BuChE by these compounds was approximately the same, or better, when
      acetylthiocholine, the analog of the neurotransmitter acetylcholine, was used as
      the substrate, instead of butyrylthiocholine. In addition, for these drugs, the
      inhibition of aryl acylamidase activity paralleled that observed for inhibition
      of esterase activity of AChE and BuChE. Given that drugs that are currently in
      use for the treatment of Alzheimer disease inhibit both AChE and BuChE, the
      development of drugs targeted toward the exclusive inhibition of one or the other
      cholinesterase may be important for understanding the relative importance of
      inhibition of BuChE and AChE in the treatment of this disease.

PMID- 12794391
TI  - Research advances in the neurology of dementia.

PMID- 12794392
TI  - 2nd Asia-Pacific regional meeting of the International Working Group on
      Harmonization of Dementia Drug Guidelines: meeting report.
AB  - The 2nd Asia-Pacific regional meeting of the International Working Group on
      Harmonization of Dementia Drug Guidelines (IWGH) was held in Beijing, China in
      late 2002. Representatives from over a dozen countries convened to present data
      on dementia within the region and to share information on locally adapted outcome
      measures for use in dementia clinical trials. The IWGH recognized the competency
      and capability of many Asian sites and endorsed their inclusion in future
      multicenter clinical dementia research activities.

PMID- 12794393
TI  - Comment on "American Indians/Alaska natives and dementia".

PMID- 12794394
TI  - Incidence of acute lung injury in the United States.
AB  - OBJECTIVE: Recent estimates of acute respiratory distress syndrome (ARDS)
      incidence have varied from 1.3 to 22 per 100,000 person years (105 person.years);
      the incidence of acute lung injury (ALI) has varied from 17.9 to 34 cases per 105
      person.years. Potential reasons for this wide range include differences in the
      definition of the syndrome, in the populations sampled, and in the assumptions
      made to estimate incidence. We hypothesized that careful, prospective, protocol
      driven case identification that included the milder hypoxemia criterion for ALI
      would yield incidence numbers greater than previously reported. DESIGN:
      Prospective cohort study with extrapolation to the U.S. population. SETTING:
      National Heart, Lung, and Blood Institute-sponsored ARDS Network composed of 20
      hospitals. PATIENTS: As part of the National Institutes of Health-sponsored ARDS
      network, 20 hospitals prospectively identified patients with ALI from 1996 to
      1999. Screening logs from this study were used to estimate ALI rates per
      intensive care unit (ICU) bed per year. We used the registry and data from the
      American Hospital Association to estimate the incidence of ALI in the United
      States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ALI per ICU bed
      incidence in the ARDS network registry varied from 0.7 to 5.8 cases of ALI per
      ICU bed per year with an average of 2.2 cases of ALI per ICU bed per year. We
      tested the robustness of the incidence estimate by performing a variety of
      sensitivity analyses. When we used the conservative assumptions that the ARDS
      network screening logs were complete at each of the participating hospitals and
      that ALI cases are limited to academic hospitals with > or =20 adult ICU beds,
      the incidence of ALI in adults in the United States is 22.4 cases per 105
      person.years. Under the less conservative assumption that ALI cases occurred only
      at hospitals with > or =20 ICU beds, regardless of their academic status, the
      incidence of ALI in the United States is estimated at 64.2 cases per 105
      person.years. CONCLUSIONS: Based on this analysis, which used prospective
      clinical trial screening data and conservative assumptions about where patients
      with ALI are cared for, the incidence of ALI in the United States appears to be
      higher than previously reported.

PMID- 12794395
TI  - Recombinant platelet-activating factor acetylhydrolase to prevent acute
      respiratory distress syndrome and mortality in severe sepsis: Phase IIb,
      multicenter, randomized, placebo-controlled, clinical trial.
AB  - OBJECTIVE: Platelet-activating factor (PAF) is a potent proinflammatory mediator
      implicated in the pathogenesis of both severe sepsis and acute respiratory
      distress syndrome. One of the regulatory pathways for PAF involves degradation to
      the inactive metabolite lyso-PAF by the enzyme PAF acetylhydrolase (PAF-AH).
      Because reduced concentrations of the natural form of PAF-AH have been reported
      in septic patients, the present study was conducted to determine whether
      treatment with recombinant human PAF-AH (rPAF-AH, Pafase) was safe when
      administered after the onset of severe sepsis and whether it decreases the
      prevalence of acute respiratory distress syndrome and 28-day all-cause mortality.
      DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter
      trial. SETTING: Thirty-three medical and surgical intensive care units located in
      the United States. PATIENTS: A total of 127 patients with severe sepsis, but
      without established acute respiratory distress syndrome, were enrolled in the
      study. Randomization occurred within 12 hrs of the onset of severe sepsis.
      Patients then received 1.0 mg/kg rPAF-AH (n = 45), 5.0 mg/kg rPAF-AH (n = 39), or
      placebo (n = 43) administered intravenously, once daily, for five consecutive
      days. MEASUREMENTS AND MAIN RESULTS: Demographic and baseline clinical
      characteristics of the three treatment groups were similar, except for a
      significantly higher prevalence of respiratory tract infections as the cause of
      severe sepsis in patients treated with 1.0 mg/kg rPAF-AH. There were no treatment
      related deaths, and the overall prevalence of adverse events was similar among
      rPAF-AH-treated and placebo-treated patients. There were no significant
      differences in the prevalence of acute respiratory distress syndrome among the
      three treatment groups. However, 28-day all-cause mortality was 21% in the 1.0
      mg/kg rPAF-AH group, 28% in the 5.0 mg/kg rPAF-AH group, and 44% in the placebo
      group (overall chi-square p =.07; 1.0 mg/kg rPAF-AH vs. placebo, p =.03). A trend
      toward reduced multiple organ dysfunction also was observed in the 1.0 mg/kg rPAF
      AH group compared with the placebo group (p =.11). CONCLUSION: The results from
      this study indicate that rPAF-AH was well tolerated and should be pursued as a
      potential new treatment to decrease mortality in patients with severe sepsis.

PMID- 12794396
TI  - Association of outcomes with organizational characteristics of neonatal intensive
      care units.
AB  - OBJECTIVE: Health outcomes may be influenced by organizational and management
      characteristics. We hypothesized that neonatal intensive care unit managerial
      practices and organizational processes could affect outcomes of births 500-1499
      g, and we assessed this in eight neonatal intensive care units. DESIGN: Multiple
      center cohort. SETTING: Eight acute care neonatal intensive care units in
      Washington, DC. PATIENTS: Infants weighing 500-1499 g, born from October 1, 1994,
      to February 19, 1997, to a resident of Washington, DC. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Outcomes included 28-day survival/death,
      bronchopulmonary dysplasia (BPD), periventricular/intraventricular hemorrhage or
      periventricular leukomalacia (PIVH/PVL), retinopathy of prematurity (ROP), length
      of hospital stay, and days of mechanical ventilation. Managerial practices and
      organizational processes were rated by nurses (n = 218), physicians (n = 73), and
      respiratory therapists (n = 77). Risk-adjusted logistic and linear mixed models
      were used to assess the association of outcomes with the caregiver ratings. A
      lower incidence of PIVH/PVL was associated with better overall scores (p =.0036)
      and better subscores for leadership (p <.0001), coordination (p =.047), and
      conflict resolution (p =.020). Better values of the respiratory therapists',
      nurses', and physicians' scores were associated with lower mortality rates (p
      =.045) and BPD (p =.0057), PIVH/PVL (p <.0001), and ROP (p =.049), respectively.
      In multivariate analysis, the joint effects of the professional groups' scores
      were associated with the incidence of PIVH/PVL (p =.0047); the nurses' scores
      were associated with lower incidence of PIVH/PVL (p =.0051). The association
      between the respiratory therapists' scores and lower mortality rate (p =.025)
      also remained significant in multivariate analysis. CONCLUSIONS: We found that
      the organizational processes and managerial practices as rated by healthcare
      professionals in neonatal intensive care units were associated with the
      development of mortality and chronic, severe morbidity. We did not identify
      specific processes or practices that accounted for our results.

PMID- 12794397
TI  - Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation
      and induces gut epithelial cell cycle arrest.
AB  - OBJECTIVES: To evaluate whether the up-regulation in sepsis-induced gut
      epithelial apoptosis is balanced by an increase in intestinal proliferation and
      to assess mechanisms affecting the gut's regenerative response to overwhelming
      infection. DESIGN: Prospective, randomized, controlled study. SETTING: Animal
      laboratory in a university medical center. INTERVENTIONS: Mice were subjected to
      intratracheal injection of Pseudomonas aeruginosa and killed between 1.5 and 24
      hrs after induction of pneumonia-induced sepsis to assess for gut epithelial
      proliferation and cell division and for apoptosis. Animals were compared with
      sham-operation controls, septic transgenic mice that overexpress Bcl-2 throughout
      their small intestinal epithelium, and septic p53-/- mice. MEASUREMENTS AND MAIN
      RESULTS: Proliferation and cell division were assessed by measuring S-phase and M
      phase cells in intestinal crypts. The number of S-phase cells showed a
      progressive decline at all time points measured, with a 5-fold decrease in
      proliferation between control animals and septic mice 24 hrs after intratracheal
      injection of pathogenic bacteria (p <.0001). In contrast, cells in M-phase
      remained constant for the first 12 hrs after the onset of sepsis, but increased
      nearly 50% at 24 hrs after instillation of P. aeruginosa (p <.005). Both the
      decrease in S-phase cells and the increase in M-phase cells were partially
      suppressible in Bcl-2 overexpressors, but cellular proliferation and division
      were similar between septic p53-/- and p53+/+ mice. Crypt apoptosis was increased
      at all time points, with maximal death occurring between 12 and 24 hrs.
      CONCLUSIONS: Sepsis from P. aeruginosa pneumonia induces a p53-independent
      decrease in gut epithelial proliferation. Despite an increase in sepsis-induced
      intestinal apoptosis, there is no compensatory increase in intestinal epithelial
      proliferation, and there is evidence of a cell cycle block with an accumulation
      of cells in M-phase. Decreasing gut apoptosis by overexpression of Bcl-2 is
      associated with a partial reversal of the effect of sepsis on the cell cycle.

PMID- 12794398
TI  - Automated intensive care unit risk adjustment: results from a National Veterans
      Affairs study.
AB  - CONTEXT: Comparison of outcome among intensive care units (ICUs) requires risk
      adjustment for differences in severity of illness and risk of death at admission
      to the ICU, historically obtained by costly chart review and manual data entry.
      OBJECTIVE: To accurately estimate patient risk of death in the ICU using data
      easily available in hospital electronic databases to permit automation. DESIGN
      AND SETTING: Cohort study to develop and validate a model to predict mortality at
      hospital discharge using multivariate logistic regression with a split derivation
      (17,731) and validation (11,646) sample formed from 29,377 consecutive first ICU
      admissions to medical, cardiac, and surgical ICUs in 17 Veterans' Health
      Administration hospitals between February 1996 and July 1997. MAIN OUTCOME
      MEASURES: Mortality at hospital discharge adjusted for age, laboratory data,
      diagnosis, source of ICU admission, and comorbid illness. RESULTS: The overall
      hospital death rate was 11.3%. In the validation sample, the model separated well
      between survivors and nonsurvivors (area under the receiver operating
      characteristic curve = 0.885). Examination of the observed vs. the predicted
      mortality across the range of mortality showed the model was well calibrated.
      CONCLUSIONS: Automation could broaden access to risk adjustment of ICU outcomes
      with only a small trade-off in discrimination. Broader use might promote valid
      evaluation of ICU outcomes, encouraging effective practices and improving ICU
      quality.

PMID- 12794399
TI  - Lipid composition and lipopolysaccharide binding capacity of lipoproteins in
      plasma and lymph of patients with systemic inflammatory response syndrome and
      multiple organ failure.
AB  - BACKGROUND: Lipopolysaccharide (LPS), the major glycolipid component of Gram
      negative bacterial outer membranes, is a potent endotoxin responsible for many of
      the directly or indirectly induced symptoms of infection. Lipoproteins (in
      particular, high-density lipoproteins) sequester LPS, thereby acting as a humoral
      detoxification mechanism. PATIENTS: Differences in the lipoprotein composition in
      human plasma and lymph of a control patient group (n = 5) without systemic
      inflammatory response syndrome (non-SIRS/MOF) and patients with SIRS and multiple
      organ failure (MOF, n = 9) were studied. The LPS binding capacity of the
      lipoproteins in SIRS/MOF and non-SIRS/MOF patients was investigated by
      rechallenge of the plasma and lymph with fluorescently labeled LPS ex vivo. The
      lipoprotein composition was analyzed using immunochemical techniques and high
      performance gel permeation chromatography. RESULTS: In the non-SIRS/MOF patient
      group, plasma and lymph levels of apolipoprotein A-I (600 and 450 mg/L,
      respectively), apolipoprotein B (440 and 280 mg/L, respectively), total
      cholesterol (2.88 and 1.05 mM, respectively), and total triglycerides (0.67 and
      0.97 mM, respectively) were observed. In the SIRS/MOF group, a decrease of
      apolipoprotein A-I (-55% in plasma and lymph), a decrease of apolipoprotein B (
      43% in plasma and -38% in lymph), and a decrease of total cholesterol levels (
      54% in plasma and -37% in lymph) were demonstrated. However, the triglyceride
      levels in the SIRS/MOF group showed a 30% increase in plasma and a 47% decrease
      in lymph compared with the non-SIRS/MOF patients. In SIRS/MOF patients, a 2.8
      fold increase in plasma and a 1.8-fold increase in lymph of the LPS low-density
      lipoprotein/high-density lipoprotein ratio was observed, indicating that the
      relative LPS binding capacity of the lipoproteins in the SIRS/MOF patient group
      showed a trend to be shifted mainly toward low-density lipoproteins. Furthermore,
      in plasma and lymph of four SIRS/MOF patients, a novel cholesterol-containing
      high-density lipoprotein-like particle was found that barely had LPS binding
      capacity (<5%). CONCLUSIONS: In the SIRS/MOF patients, the changes in lipoprotein
      composition in lymph are a reflection of those in plasma, except for the
      triglyceride levels. In comparison with the non-SIRS/MOF patients, the SIRS/MOF
      patients show a shifted LPS binding capacity of high-density lipoproteins toward
      low-density lipoproteins in plasma and in lymph. Moreover, in plasma and lymph,
      novel cholesterol-containing particles, resembling high-density lipoprotein, were
      identified in the SIRS/MOF patient group.

PMID- 12794400
TI  - A discard volume of twice the deadspace ensures clinically accurate arterial
      blood gases and electrolytes and prevents unnecessary blood loss.
AB  - OBJECTIVE: To determine the blood discard volume, as a multiple of deadspace,
      that is required for accurate arterial blood gas and electrolyte testing from
      arterial catheters. DESIGN: Prospective, controlled, crossover trial. SETTING:
      Eighteen-bed intensive care unit of a metropolitan teaching hospital. PATIENTS: A
      total of 84 critically ill patients with a 20-gauge, radial arterial cannulae,
      pressure monitoring transducer set, and stable oxygenation. INTERVENTIONS: System
      deadspace (priming volume from sampling port to catheter tip) was established.
      Patients had six 0.5-mL arterial blood samples taken sequentially in random order
      using discard volumes of 1, 1.5, 2, 2.3, and 3.6 times the deadspace
      (experimental values) and 5.5 times the deadspace (control). MEASUREMENTS AND
      MAIN RESULTS: Samples were analyzed for Pao(2), Sao(2), pH, Paco(2), HCO(3)-,
      Na+, and K+. We performed repeated-measures analysis of variance with post hoc
      linear contrasts and compared mean experimental and control values. The smallest
      discard volumes that provided measurements that were statistically equal to
      control were twice the deadspace (Pao(2), p =.563; Sao(2), p =.371) and 3.6 times
      the deadspace (pH, p =.107; Paco(2), p=.519; HCO(3)-, p =.10). All discard
      volumes tested provided results that were statistically different from control
      for Na+ (p <.003) and K+ (p <.001). CONCLUSIONS: Many results were statistically
      different from control, although the actual discrepancies were very small. At
      clinically relevant levels of measurement, there was minimal variation between
      values obtained after a discard volume of twice the deadspace and control values.
      The level of error was clinically acceptable and within or close to the precision
      limits of the blood gas analyzer. Slight fluctuation in patient variables during
      sampling could also have contributed to the error. A blood discard volume of
      twice the deadspace is recommended for all variables. This will provide
      clinically accurate results and avoid the deleterious effects of unnecessary
      blood loss.

PMID- 12794401
TI  - Effects of dopamine, norepinephrine, and epinephrine on the splanchnic
      circulation in septic shock: which is best?
AB  - OBJECTIVE: To assess the effects of different doses of dopamine, norepinephrine,
      and epinephrine on the splanchnic circulation in patients with septic shock.
      DESIGN: Prospective, randomized, open-label study. SETTING: A 31-bed,
      medicosurgical intensive care unit of a university hospital. PATIENTS:
      Convenience sample of 20 patients with septic shock, separated into two groups
      according to whether (moderate shock group, n = 10) or not (severe shock, n = 10)
      dopamine alone was able maintain mean arterial pressure >65 mm Hg. INTERVENTIONS:
      Dopamine was progressively withdrawn and replaced successively by norepinephrine
      and then epinephrine (the order of the two agents was randomly determined) to
      maintain mean arterial pressure constant (moderate shock) or to increase mean
      arterial pressure above 65 mm Hg (severe shock). MEASUREMENTS AND MAIN RESULTS:
      Systemic circulation (pulmonary artery catheter) and splanchnic circulation
      (indocyanine green dilution and hepatic vein catheter) and gastric mucosal Pco(2)
      (gas tonometry) were measured during dopamine (moderate shock only),
      norepinephrine, and epinephrine administration (both groups). Data were analyzed
      with nonparametric tests and are presented as median [percentiles 25-75]. In
      moderate shock, cardiac index was similar to dopamine and norepinephrine (3.1
      [2.7-3.8] vs. 2.9 [2.7-4.1] L/min.m2, p = nonsignificant) but greater with
      epinephrine (4.1 [3.5-4.4] p <.01 vs. dopamine and norepinephrine). Splanchnic
      blood flow was similar with the three agents (732 [413-1483] vs. 746 [470-1401]
      vs. 653 [476-1832] mL/min.m, p = nonsignificant). The gradient between mixed
      venous and hepatic venous oxygen saturations was lower with dopamine than with
      norepinephrine and epinephrine, but the Pco(2) gap was similar with the three
      agents. In severe shock, cardiac index was higher, but splanchnic blood flow was
      lower, with epinephrine than with norepinephrine (4.6 [3.7-5.3] vs. 3.4 [3.0-4.1]
      L/min.m2, p <.01 and 860 [684-1334] vs. 977 [806-1802] mL/min.m2, p <.05,
      respectively). Epinephrine increased the mixed-venous and hepatic venous oxygen
      saturation gradient but did not alter Pco(2) gap. CONCLUSIONS: Dopamine and
      norepinephrine have similar hemodynamic effects, but epinephrine can impair
      splanchnic circulation in severe septic shock.

PMID- 12794402
TI  - Glucocorticoid insufficiency in patients who present to the hospital with severe
      sepsis: a prospective clinical trial.
AB  - OBJECTIVE: To identify the incidence of secondary adrenal insufficiency in severe
      sepsis. DESIGN: Prospective clinical trial testing 100 patients with a 250-microg
      adrenocorticotropic hormone (ACTH) stimulation test. SETTING: County-university
      teaching hospital. PATIENTS: One hundred patients with sepsis and septic shock.
      Forty patients had bacteremia and 17% shock. INTERVENTIONS: ACTH, cortisol,
      aldosterone, and electrolyte concentrations were measured at baseline. Cortisol
      and aldosterone were measured 30 and 60 mins after ACTH (250 microg).
      MEASUREMENTS AND MAIN RESULTS: Nine of the 100 patients (9%) failed the ACTH
      stimulation test (all serum cortisol <20 microg/dL). The 91 patients with sepsis
      began with a serum cortisol at 29.3 +/- 2.5, and it increased to 40.1 +/- 2.6 and
      46.9 +/- 2.7 microg/dL at times 30 and 60 mins, respectively. Serum cortisol in
      nine septic patients who failed the ACTH stimulation test had an initial
      concentration of 11.3 +/- 1.8 microg/dL, and it increased at time 30 mins to 14.0
      +/- 1.9 microg/dL and at 60 mins to 15.7 +/- 1.8 microg/dL. Four of the nine
      patients had secondary adrenal insufficiency as determined by a normal
      aldosterone response to ACTH. The remaining five patients had an absent
      aldosterone response to ACTH and baseline ACTH concentrations that were not
      elevated, suggesting adrenal dysfunction. Serum sodium (128 +/- 4 vs. 138 +/- 1
      mmol/L, p <.05) and glucose concentrations (121 +/- 20 vs. 163 +/- 11 mg/dL, p
      <.05) were reduced in the nine patients. Of the four patients with secondary
      adrenal insufficiency, two had a history of amenorrhea after birth of their
      children many years earlier. CONCLUSIONS: These data demonstrate that 9% of
      adults with sepsis fail the ACTH stimulation test due to a mixture of etiologies.
      A reduced sodium or glucose concentration may be helpful in identifying
      glucocorticoid (adrenal) insufficiency in patients with sepsis.

PMID- 12794403
TI  - Monitoring the evolutionary process of quality: risk-adjusted charting to track
      outcomes in intensive care.
AB  - OBJECTIVE: To present graphical procedures for prospectively monitoring outcomes
      in the intensive care unit. DESIGN: Observational study: risk-adjusted control
      chart analysis of a case series. SETTING: Tertiary referral adult intensive care
      unit: Princess Alexandra Hospital, Brisbane, Australia. PATIENTS: A total of 3398
      intensive care unit admissions from January 1, 1995, to January 1, 1998.
      CONCLUSIONS: Risk-adjusted process control charting procedures for continuous
      monitoring of intensive care unit outcomes are proposed as quality management
      tools. A modified Shewhart p chart and cumulative sum process control chart,
      using the Acute Physiology and Chronic Health Evaluation III model mortality
      prediction for risk adjustment, are presented. The risk-adjusted p chart
      summarizes performance at arbitrary intervals and plots observed against
      predicted mortality rate to detect large changes in risk-adjusted mortality. The
      risk-adjusted cumulative sum procedure is a likelihood-based scoring method that
      adjusts for estimated risk of death, accumulating evidence from outcomes of all
      previous patients. It formally tests the hypothesis of a change in the odds of
      death. In this application, we detected a decrease from above to predicted risk
      adjusted mortality. This was temporally related to increased senior staffing
      levels and enhanced ongoing multidisciplinary review of practice, quality
      improvement, and educational activities. Formulas and analyses are provided as
      appendices.

PMID- 12794404
TI  - Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of
      refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more
      effective than 2 mL/kg 20% mannitol.
AB  - OBJECTIVE: To evaluate the clinical benefit of increasing the osmotic load of the
      hypertonic solution administered for the treatment of refractory intracranial
      hypertension episodes in patients with severe head injury. DESIGN: Prospective,
      randomized study. SETTINGS: A trauma center in a university hospital. PATIENTS:
      Twenty consecutive patients with head trauma and persistent coma who required
      infusions of an osmotic agent to treat episodes of intracranial hypertension
      resistant to well-conducted standard modes of therapy were studied. Intracranial
      hypertension was considered refractory when it persisted despite deep sedation,
      optimal hemodynamic status, and, in some patients, drainage of cerebral spinal
      fluid. INTERVENTIONS: Patients were randomly assigned to receive isovolume
      infusions of either 7.5% hypertonic saline solution (2400 mOsm/kg/H(2)O) or 20%
      mannitol (1160 mOsm/kg/H(2)O). The patients were given 2 mL/kg (body weight) of
      either solution, i.e., 361 +/- 13 mOsm of saline or 175 +/- 12 mOsm of mannitol
      per injection. MEASUREMENTS AND MAIN RESULTS: The main variables studied were the
      number and the duration of episodes of intracranial hypertension per day during
      the study period, which was stopped after the last episode of intracranial
      hypertension was recorded from intracranial pressure monitoring or after the
      allocated treatment failure. Patients in the HHS group were monitored for 7 +/- 5
      days and those in the mannitol group for 7 +/- 6 days (not significant). The rate
      of failure for each treatment was also evaluated. Failure was defined as the
      persistence of intracranial hypertension despite two successive infusions of the
      same osmotic agent. The mean number of osmotic solute infusions was 3.7 +/- 5.3
      in the mannitol group and 3.3 +/- 4.1 in the hypertonic saline solution group
      (not significant). The mean number (6.9 +/- 5.6 vs. 13.3 +/- 14.6 episodes) of
      intracranial hypertension episodes per day and the daily duration (67 +/- 85 vs.
      131 +/- 123 min) of intracranial hypertension episodes were significantly lower
      in the hypertonic saline solution group (p <.01). The rate of clinical failure
      was also significantly lower in the hypertonic saline solution group: 1 of 10
      patients vs. 7 of 10 patients (p <.01). CONCLUSION: In this study, when a
      hypertonic solute was required for the treatment of refractory intracranial
      hypertension episodes in patients with severe head trauma, increasing the osmotic
      load by giving 2 mL/kg (body weight) of 7.5% saline (361 +/- 13 mOsm) was more
      effective than giving 2 mL/kg (body weight) of 20% mannitol (175 +/- 12 mOsm).
      Within the limitations of the present study, these data suggest that giving 2
      mL/kg hypertonic saline solution (approximately 480 mOsm/70 kg body weight) is an
      effective and safe initial treatment for intracranial hypertension episodes in
      head-trauma patients when osmotherapy is indicated.

PMID- 12794405
TI  - Each lumen is a potential source of central venous catheter-related bloodstream
      infection.
AB  - OBJECTIVE: To determine the relative rates of microbial colonization of
      individual lumens in triple-lumen central venous catheters (CVCs) and calculate
      the chance of detecting catheter-related blood stream infection (CRBSI) if only
      one lumen is sampled. DESIGN: Prospective evaluation of CVCs from suspected and
      nonsuspected CRBSI cases. SETTING: University teaching hospital. PATIENTS: Triple
      lumen CVCs from 50 cases of suspected CRBSI (a raised peripheral white blood cell
      count, temperature >37 degrees C, and/or local signs of infection at the catheter
      skin entry site) were evaluated. For comparison, 50 triple-lumen CVCs routinely
      removed at the end of use were evaluated. MEASUREMENTS: In both groups,
      peripheral blood cultures were taken before CVC removal. After CVC removal, each
      lumen was sampled in vitro using the endoluminal brush, and the tip was then
      cultured using the Maki roll technique. MAIN RESULTS: CVCs causing CRBSI had
      significant microbial colonization in one, two, or three lumens in ten (40%), ten
      (40%), or five (20%) cases, respectively. Overall, random sampling of only one
      lumen in CVCs causing CRBSI had a 60% chance of detecting significant
      colonization. CONCLUSIONS: If only one CVC lumen is sampled, a negative result
      does not reliably rule out infection. Each lumen of multiple-lumen CVCs should be
      considered as a potential source of CRBSI.

PMID- 12794406
TI  - Methodologic quality and genotyping reproducibility in studies of tumor necrosis
      factor -308 G-->A single nucleotide polymorphism and bacterial sepsis:
      implications for studies of complex traits.
AB  - OBJECTIVE: Studies of genetic associations with common diseases, such as between
      cytokine gene polymorphisms and severe bacterial sepsis, have reached conflicting
      conclusions. Failure to follow methodologic standards may have contributed to
      discordant findings. The -308 G-->A transition in the tumor necrosis factor-alpha
      promoter has been genotyped by a variety of methods. Based on our observation of
      genotyping inaccuracies, we sought to determine whether published studies
      followed a series of acceptable methodologic standards and whether failure to
      follow the standard of genotyping reproducibility could lead to erroneous
      conclusions about gene-disease associations. DESIGN: Systematic review and
      reanalysis of banked genetic material. We applied a published series of seven
      methodologic standards to five reports of the association between this variant
      and bacterial sepsis. We then studied the accuracy of restriction fragment length
      polymorphism for the -308 site using DNA from a cohort of injury victims.
      SETTING: Surgery research laboratory. MEASUREMENTS AND MAIN RESULTS: We observed
      that methodologic quality was not uniform and that reproducibility of genotyping
      was infrequently met. In our subjects, we found that 4 of 46 heterozygotes
      analyzed by restriction fragment length polymorphism were actually GG-homozygotes
      (9% misclassified) according to alternative genotyping methods. CONCLUSIONS:
      Failure to confirm genotype may have led to conclusions that this polymorphism is
      not associated with sepsis or outcome. Our observations have implications for the
      conduct and evaluation of studies of complex genetic disease.

PMID- 12794407
TI  - Inhaled nitric oxide inhibits platelet-leukocyte interactions in patients with
      acute respiratory distress syndrome.
AB  - INTRODUCTION: In addition to its effects on platelet function, recent studies
      suggest that inhaled nitric oxide (NO) also influences the function of
      circulating leukocytes. Therefore, the aim of this work was to investigate the
      formation of platelet-leukocyte aggregates (PLAs) and platelet and leukocyte cell
      surface receptor expression during NO therapy in patients with acute respiratory
      distress syndrome. METHODS: In 16 patients responding to NO therapy with an
      improvement in oxygenation (NO group) and in four nonresponders (control),
      platelet P-selectin expression, platelet fibrinogen binding, the expression CD11a
      on leukocytes, and the formation of PLAs were investigated at 0, 60, 120, and 180
      mins of therapy or at corresponding time points by means of flow cytometry. In
      addition, PLA was investigated in 30 healthy volunteers during NO inhalation, in
      five mechanically ventilated patients without acute respiratory distress syndrome
      and without NO inhalation, and during NO incubation in platelet-rich plasma of
      ten healthy volunteers in vitro. RESULTS: NO therapy inhibited PLA formation at
      60 (13% +/- 4% in the NO group vs. 19% +/- 7% in the control group, p <.01) and
      120 mins (14% +/- 4% vs. 18% +/- 7%, p <.05) and slightly decreased CD11a
      expression at 60 mins (152 +/- 22 arbitrary units vs. 187 +/- 36 arbitrary units,
      p <.05). Furthermore, besides inhibiting platelet fibrinogen binding, NO also led
      to a significant inhibition of P-selectin expression at 120 (38% +/- 4% vs. 43%
      +/- 5%, p <.05) and 180 mins (34% +/- 5% vs. 43% +/- 6%, p <.01), demonstrating a
      significant correlation between changes in P-selectin expression and PLA
      formation. In contrast, PLA formation was not influenced by mechanical
      ventilation in patients without acute respiratory distress syndrome. These
      results were further supported by additional studies showing inhibition of PLA
      formation in healthy volunteers as well. CONCLUSIONS: NO-dependent inhibition of
      PLA formation in patients with acute respiratory distress syndrome can be
      explained by the inhibition in platelet P-selectin expression. Thus, this study
      provides rational evidence of systemic antileukocytic and antiplatelet properties
      of NO therapy in the clinical setting.

PMID- 12794408
TI  - Assessment of microvascular oxygen saturation in gastric mucosa in volunteers
      breathing continuous positive airway pressure.
AB  - OBJECTIVE: Adequate oxygenation of the gastrointestinal mucosa to preserve its
      barrier function is a basic objective in the prevention of multiple organ
      failure. Sustaining a positive airway pressure during the entire respiratory
      cycle remains a cornerstone in the therapeutic regimen to improve systemic
      oxygenation. Whereas increased systemic oxygenation during breathing continuous
      positive airway pressure has been shown, the impact of continuous positive airway
      pressure on regional oxygenation in the gastrointestinal tract has not yet been
      evaluated. We hypothesized that continuous positive airway pressure decreases
      microvascular oxygen saturation in gastric mucosa. DESIGN: Prospective,
      randomized study. SETTING: University department of anesthesiology. PARTICIPANTS:
      Twelve healthy volunteers. INTERVENTIONS: Incremental increases of continuous
      positive airway pressure (0, 5, and 10 cm H(2)O) and subsequent release of
      continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS: We
      continuously measured microvascular oxygen saturation in gastric mucosa by
      reflectance spectrophotometry. Systemic oxygen saturation, end-tidal Pco(2),
      respiratory rate, heart rate, and arterial blood pressure were obtained
      noninvasively. In every volunteer, microvascular oxygen saturation in gastric
      mucosa was reduced corresponding to the level of continuous positive airway
      pressure, although systemic variables, especially systemic oxygen saturation, did
      not change. Continuous positive airway pressure reduced microvascular oxygen
      saturation in gastric mucosa from 59 +/- 7% (baseline with 0 cm H(2)O continuous
      positive airway pressure, mean +/- sd) to 54 +/- 8% (p <.05) during 5 cm H(2)O
      continuous positive airway pressure and to 50 +/- 9% (p <.05) during 10 cm H(2)O
      continuous positive airway pressure, returning to 59 +/- 7% during spontaneous
      breathing with 0 cm H(2)O continuous positive airway pressure. End-tidal Pco(2),
      respiratory rate, as well as hemodynamic variables, remained stable. CONCLUSIONS:
      Reflectance spectrophotometry meticulously monitored changes in microvascular
      oxygen saturation in gastric mucosa during breathing continuous positive airway
      pressure. Microvascular oxygen saturation in gastric mucosa decreased with
      increasing levels of continuous positive airway pressure despite steady systemic
      variables. These results suggest that the impact of altering airway pressures on
      splanchnic oxygenation is not mirrored necessarily by concomitant changes in
      systemic circulation. Moreover, if these findings also apply to critically ill
      patients, monitoring microvascular oxygen saturation in gastric mucosa would be
      useful to further optimize the setting of ventilation variables.

PMID- 12794410
TI  - Intensive care unit support and Acute Physiology and Chronic Health Evaluation
      III performance in hematopoietic stem cell transplant recipients.
AB  - OBJECTIVE: Hematopoietic stem cell transplant (HSCT) recipients admitted to the
      intensive care unit (ICU) have high mortality. The prognostic importance of
      peripheral blood stem cell source in critically ill HSCT recipients and the
      performance of Acute Physiology and Chronic Health Evaluation (APACHE) III have
      not been well studied. In a previous study, the hospital mortality rate of HSCT
      recipients admitted to our ICU was 77%. The objectives of this study were to
      describe the clinical course of HSCT recipients admitted to the ICU and to
      determine the performance of APACHE III in predicting their mortality. DESIGN:
      Retrospective cohort study. SETTING: Academic medical center. PATIENTS: HSCT
      recipients admitted to the ICU. MEASUREMENTS: Demographics, transplant type, stem
      cell source, APACHE II and III predicted mortality, development of sepsis and
      organ failure, use of mechanical ventilation, duration of hospital stay, and
      mortality. RESULTS: Ninety-four percent of the 112 HSCT recipients were white and
      64% male. The mean APACHE II and III scores were 25 and 44, respectively. The
      APACHE II and III hospital predicted mortality rates were 44% and 42%,
      respectively. Mechanical ventilation was provided to 63%. Organ failure developed
      in 94% and sepsis in 62%. The ICU, hospital, and 30-day mortality rates were 33%,
      46%, and 52%, respectively. Allogeneic transplant and higher APACHE III scores,
      but not bone marrow stem cell source, were associated with increased mortality.
      Invasive mechanical ventilation, vasoactive medication use, sepsis, and organ
      failure during patients' ICU course were also associated with increased
      mortality. The area under the receiver operating characteristic curve for APACHE
      III hospital mortality prediction was 0.704 (95% confidence interval, 0.610
      0.786). For APACHE III hospital mortality prediction, the value of the Hosmer
      Lemeshow statistic showed good model fit. CONCLUSIONS: Current mortality figures
      of HSCT recipients admitted to the ICU are better than previously reported. The
      APACHE III prognostic model has moderate discrimination and good calibration in
      predicting hospital mortality in these patients.

PMID- 12794409
TI  - Opinions about surrogate designation: a population survey in France.
AB  - OBJECTIVE: Many patients go through periods when they are too ill to give consent
      or to participate in decisions. When this occurs, patient autonomy is best
      maintained when a surrogate designated by the patient and familiar with his or
      her values can speak for the patient. The objective of this study was to
      determine whether people who are not yet ill are ready to accept surrogate
      designation. Attitudes toward family participation in care were explored also.
      DESIGN: Population survey by telephone. Because refusal of life-sustaining
      treatment is a dramatic example of patient autonomy, the survey used questions
      about ICU admission. SETTING: General population in France. SUBJECTS:
      Representative random sample of 8000 residents of France aged 18 yrs or more.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: The survey investigated attitudes.
      RESULTS: Most respondents said they would like to designate a surrogate (7205
      [90%]) and to have their family share in their care (6691 [84%] for bathing, 5629
      [70%] for feeding, and 4139 [52%] for tracheal suctioning) and in decisions about
      their management (6120 [76%]). Among respondents with a spouse, 79% said they
      would designate the spouse to speak for them. The attitudes were not influenced
      by ethnicity, religion or education level. CONCLUSIONS: Most people living in
      France would want a surrogate to represent them should they be incompetent and
      admitted to an ICU. Primary care physicians should inform their patients about
      the benefits of discussing illness-related issues among friends and family.

PMID- 12794411
TI  - Depressed interleukin-12-producing activity by monocytes correlates with adverse
      clinical course and a shift toward Th2-type lymphocyte pattern in severely
      injured male trauma patients.
AB  - OBJECTIVE: To determine the effect of major trauma on the cytokine-producing
      activity of monocytes and CD4+ T cells in a homogeneous cohort of patients as
      well as to determine the relationship between monocyte and T-lymphocyte responses
      and clinical outcome. SETTINGS: Surgical intensive care units of a trauma center
      and flow cytometry and experimental laboratories at a teaching hospital. DESIGN:
      Prospective cohort clinical study with measurements of white cell cytokine
      producing activity on days 2, 5, and 10 postinjury. The number of cytokine
      producing CD14+ monocytes, CD4+, and CD8+ T cells were determined in whole blood
      using flow cytometry combined with the intracellular cytokine staining method.
      Basal and lipopolysaccharide-stimulated interleukin (IL)-12, tumor necrosis
      factor-alpha, IL-6, and IL-1alpha production by monocytes as well as basal and
      phorbol 12-myristate 13-acetate plus ionomycin-stimulated interferon-gamma, IL-4,
      and tumor necrosis factor-alpha production by T cells were determined on days 2,
      5, and 10 postinjury and compared with similar measurements made in healthy
      control subjects. PATIENTS: Twelve randomly selected black, male patients were
      enrolled in the study: mean injury severity score, 26; mean age, 35 yrs; mean
      Glasgow Coma Scale score, 13; systemic inflammatory response syndrome, 92%;
      sepsis, 42%; bronchial infection, 42%; and adult respiratory distress syndrome
      25%. MAIN RESULTS: After lipopolysaccharide stimulation, the number of IL-12-,
      tumor necrosis factor-alpha-, IL-1alpha-, and IL-6-producing CD14+ monocytes was
      40% to 70% lower in trauma patients on postinjury days 2, 5, and 10 than in
      healthy control subjects. After phorbol 12-myristate 13-acetate stimulation, the
      number of IL-4-producing CD4+ cells increased three-fold in the trauma patients
      compared with healthy control subjects. In contrast, the number of interferon
      gamma- or tumor necrosis factor-alpha-producing CD4+ and CD8+ T cells was not
      different between the patients and control subjects. The Th1/Th2 ratio was
      significantly lower in patients on all postinjury days than in the control
      subjects. A statistically significant inverse correlation was found between the
      number of IL-12-producing monocytes and IL-4-producing CD4+ T cells in trauma
      patients (p =.007, r2 =.47). This correlation was absent in control subjects. The
      degree of depressed capacity of monocyte IL-12 production on day 2 postinjury
      showed a statistically significant correlation with the development of adult
      respiratory distress syndrome, sepsis, or infections and also with the duration
      of systemic inflammatory response syndrome and sepsis. CONCLUSIONS: Major trauma
      results in an early and marked decrease in monocyte cytokine-producing activity.
      The trauma-induced depression in IL-12 production by the mononuclear phagocyte
      system may promote T-cell commitment toward a Th2 pattern early after trauma. The
      appearance of the Th2 pattern is the result of elevated numbers of IL-4-producing
      cells without major alterations in T-cell interferon-gamma-producing capacity.
      The degree of alterations in monocyte and T-cell responses on day 2 postinjury
      correlates with the development of adverse clinical outcomes and the subsequent
      duration of the inflammatory response.

PMID- 12794412
TI  - Plasma exchange as rescue therapy in multiple organ failure including acute renal
      failure.
AB  - OBJECTIVE: To describe the outcome of using a rescue therapy including plasma
      exchange given to patients with a progressive acute disseminated intravascular
      coagulation and multiple organ dysfunction syndrome. STUDY DESIGN: Retrospective
      study. SETTING: University and county hospital. PATIENTS: Included were 76
      consecutive patients (41 men and 35 women) treated with plasma exchange as rescue
      therapy besides optimal conventional therapy during a progressive course of
      disseminated intravascular coagulation and multiple organ dysfunction syndrome,
      including acute renal failure. Of the 76 patients, 66% needed dialysis. The
      distribution was hemodialysis in 76%, continuous arteriovenous hemofiltration in
      36%, continuous venovenous hemodialysis in 12%, and peritoneal dialysis in 24%.
      The median organ-failure score was 5 (range, 1-6). Seventy-two percent required
      mechanical ventilation; septic shock was present in 88%. The median septic shock
      score was 4 (range, 2-4). Nine patients had another reason than sepsis for the
      multiple organ dysfunction syndrome. INTERVENTION: Plasma exchange
      (centrifugation technique) was performed until disseminated intravascular
      coagulation was reversed (median, two times; range, 1-14). Besides antibiotics
      and fluid administration, most patients received heparin or low molecular weight
      heparin (77%), steroids (87%), and inotropes (88%). More than one vasoactive drug
      was used in 57% of the patients. MEASUREMENTS AND MAIN RESULTS: Eighty-two
      percent of the patients survived and could leave the hospital. The previously
      observed survival rates by others for this category of patients would be <20%,
      and thus, the outcome in this study is significantly better. CONCLUSION: Plasma
      exchange using plasma as replacement may, in addition to conventional intensive
      care, help to reverse severe progressive disseminated intravascular coagulation
      and multiple organ dysfunction syndrome and improve survival.

PMID- 12794413
TI  - Comparison of procalcitonin and C-reactive protein as markers of sepsis.
AB  - OBJECTIVE: To compare the clinical informative value of procalcitonin (PCT) and C
      reactive protein (CRP) plasma concentrations in the detection of infection and
      sepsis and in the assessment of severity of sepsis. DESIGN: Prospective study.
      SETTING: Medicosurgical intensive care unit. PATIENTS: Seventy consecutive adult
      patients who were admitted to the intensive care unit for an expected stay >24
      hrs. INTERVENTIONS: None. MEASUREMENTS: PCT and CRP plasma concentrations were
      measured daily during the intensive care unit stay. Each patient was examined
      daily for signs and symptoms of infection and was classified daily in one of the
      following four categories according to the American College of Chest
      Physicians/Society of Critical Care Medicine criteria: negative, systemic
      inflammatory response syndrome, localized infection, and sepsis group (sepsis,
      severe sepsis, or septic shock). The severity of sepsis-related organ failure was
      assessed by the sepsis-related organ failure assessment score. MAIN RESULTS: A
      total of 800 patient days were classified into the four categories. The median
      plasma PCT concentrations in noninfected (systemic inflammatory response
      syndrome) and localized-infection patient days were 0.4 and 1.4 ng/mL (p <.0001),
      respectively; the median CRP plasma concentrations were 79.9 and 85.3 mg/L (p
      =.08), respectively. The area under the receiver operating characteristic curve
      was 0.756 for PCT (95% confidence interval [CI], 0.675-0.836), compared with
      0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median plasma PCT
      concentrations in nonseptic (systemic inflammatory response syndrome) and septic
      (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p
      <.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001),
      respectively. The area under the receiver operating characteristic curve was
      0.925 for PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622
      0.733) (p <.0001). The linear correlation between PCT plasma concentrations and
      the four categories was much stronger than in the case of CRP (Spearman's rho,
      0.73 vs. 0.41; p <.05). A rise in sepsis-related organ failure assessment score
      was related to a higher median value of PCT but not CRP. CONCLUSION: PCT is a
      better marker of sepsis than CRP. The course of PCT shows a closer correlation
      than that of CRP with the severity of infection and organ dysfunction.

PMID- 12794414
TI  - Dexamethasone reduces postoperative troponin levels in children undergoing
      cardiopulmonary bypass.
AB  - OBJECTIVE: We previously demonstrated that dexamethasone treatment before
      cardiopulmonary bypass in children reduces the postoperative systemic
      inflammatory response. The purpose of this study was to test the hypothesis that
      dexamethasone administration before cardiopulmonary bypass in children correlates
      with a lesser degree of myocardial injury as measured by a decrease in cardiac
      troponin I release. DESIGN: A prospective, randomized, double-blind study.
      SETTING: The cardiac surgery operating room and intensive care unit of a
      pediatric referral hospital. SUBJECTS: Twenty-eight patients who underwent open
      heart surgery for congenital heart defects. INTERVENTIONS: Patients received
      either placebo (group I, n = 13) or dexamethasone, 1 mg/kg iv (group II, n = 15),
      1 hr before initiation of cardiopulmonary bypass. Plasma cardiac troponin I
      samples were obtained at three time points: immediately before study agent
      (sample 1), 10 mins after protamine sulfate administration after cardiopulmonary
      bypass (sample 2), and 24 hrs postoperatively (sample 3). MEASUREMENTS AND MAIN
      RESULTS: Mean cardiac troponin I levels (+/-sd) were significantly lower at
      sample time 3 in group II (dexamethasone; 33.4 +/- 20.0 ng/mL) vs. group I
      (control; 86.9 +/- 81.1) (p =.04). CONCLUSION: Dexamethasone administration
      before cardiopulmonary bypass in children resulted in a significant decrease in
      cardiac troponin I levels at 24 hrs postoperatively. We postulate that this may
      represent a decrease in myocardial injury, and, thus, a possible cardioprotective
      effect produced by dexamethasone.

PMID- 12794415
TI  - Hospital costs in patients receiving prolonged mechanical ventilation: does age
      have an impact?
AB  - BACKGROUND: The aging of the population is one of the causes of the increase in
      healthcare costs in the past few decades. It is controversial whether
      chronological age alone should be used in making healthcare decisions. OBJECTIVE:
      To determine the association between age and hospital costs in patients receiving
      mechanical ventilation (MV). DESIGN: Prospective, observational study. SETTING:
      Intensive care units at a teaching hospital. PATIENTS: A total of 813 adults who
      received prolonged (> or =48 hrs) mechanical ventilation. INTERVENTION: None.
      MEASUREMENTS: Severity of illness, comorbidities, length of stay, hospital costs,
      and mortality. We evaluated the independent association of age with hospital
      costs using linear regression. RESULTS: Mean (+/-sd) age of patients was 60.4 +/-
      18.8 yrs. Median Acute Physiology Chronic Health Evaluation III score and
      probability of hospital death at intensive care unit admission were 64 and 0.31,
      respectively. Hospital mortality was 36%. Median total hospital costs and daily
      costs were $ 56,056 and $2,655 US dollars, respectively. Older age was associated
      with lower total hospital costs after controlling for sex, intensive care unit
      type, severity of illness, length of stay, insurance type, resuscitation status,
      and survival. Hospital costs were significantly less in older patients in all
      cost departments examined, except for respiratory care and intensive care unit
      room costs. CONCLUSIONS: Daily and total hospital costs were lower in older
      patients. Decreased hospital resource use in older patients may be related to a
      preference for less aggressive care by older patients and their families or by
      healthcare providers.

PMID- 12794416
TI  - Circulating vasopressin levels in septic shock.
AB  - OBJECTIVE: To assess the frequency of vasopressin deficiency in septic shock.
      DESIGN: Prospective cohort study. SETTING: Intensive care unit at Raymond
      Poincare University Hospital. PATIENTS: A cohort of 44 patients who met the usual
      criteria for septic shock for < 7 days. A second cohort of 18 septic shock
      patients were enrolled within the first 8 hrs of disease onset. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: General demographics, severity scores, vital
      signs, standard biochemical data, and circulating vasopressin levels were
      systematically obtained at baseline in the two cohorts. Vasopressin deficiency
      was defined by a normal plasma vasopressin level in the presence of a systolic
      blood pressure of <100 mm Hg or in the presence of hypernatremia. Baroreflex
      sensitivity was systematically evaluated in patients of the first cohort when
      vasopressin deficiency was noted. In the second cohort of patients, plasma levels
      of vasopressin were obtained at baseline, 6, 24, 48, and 96 hrs after shock
      onset. In the first population, plasma vasopressin levels were inversely
      correlated to the delay from shock onset. Fourteen patients had relative
      vasopressin deficiency: 12 patients had systolic blood pressure <100 mm Hg, with
      impaired baroreflex sensitivity in four, and three patients had hypernatremia. In
      the second population, only two patients had relative vasopressin deficiency. The
      plasma levels of vasopressin significantly decreased over time (p < 10-3).
      CONCLUSIONS: Plasma vasopressin levels are almost always increased at the initial
      phase of septic shock and decrease afterward. Relative vasopressin deficiency is
      seen in approximately one-third of late septic shock patients.

PMID- 12794417
TI  - Effect of air and heliox as carrier gas on CO2 transport in a model of high
      frequency oscillation comparing two oscillators.
AB  - OBJECTIVE: To study the effect of carrier gas on CO(2) transport during high
      frequency oscillatory ventilation in a closed model. DESIGN: In vitro model
      study. SETTING: Respiratory research laboratory affiliated with a tertiary center
      for pediatric critical care. SUBJECT: In vitro, closed-lung model consisting of a
      glass tube (9.8 x 1000 mm) covered at each end with balloons. INTERVENTION: Air
      or heliox (80:20) at constant pressure was oscillated inside the model, comparing
      the Sensormedics 3100A and Hummingbird BMO-20N oscillators at equal amplitude.
      MEASUREMENTS AND MAIN RESULTS: Tracer gas (CO(2)) was injected at one end of the
      model, and CO(2) concentration was measured at the opposite end. Speed of CO(2)
      transport was expressed as the time for the CO(2) concentration to reach 63% of
      the final concentration (the time constant). In room air, using the Hummingbird
      oscillator and increasing frequency stepwise from 5 to 20 Hz, the time constant
      decreased from 2813 to 457 secs (p =.05). Using the Sensormedics oscillator in
      room air at increasing frequency from 5 to 15 Hz, the time constant decreased
      from 1584 to 551 secs (p =.05). In heliox, using the Hummingbird oscillator, the
      speed of CO(2) transport increased by 85% (p =.029) at 5 Hz and by 28% (p =.05)
      at 15 Hz. With the Sensormedics oscillator using heliox, the speed of CO(2)
      transport increased by 16% at 5 Hz (p =.009) and 52% at 15 Hz (p =.008).
      Proportionally, the increase in CO(2) transport with heliox was greater at 5 Hz
      for the Hummingbird oscillator and at 15 Hz for the Sensormedics oscillator.
      CONCLUSIONS: In a closed model, we showed that during high-frequency oscillatory
      ventilation in room air, CO(2) transport increases with increasing frequency for
      both ventilators. Using heliox as carrier gas significantly augmented CO(2)
      transport, but the increase is frequency and device dependent. The effect of
      heliox on oscillator performance and the clinical applicability of our findings
      require further study.

PMID- 12794418
TI  - Enteral nutritional supplementation prevents mesenteric lymph node T-cell
      suppression in burn injury.
AB  - OBJECTIVE: To determine the effects of an immune-enhancing diet supplemented with
      glutamine, arginine, fish oil, and dietary nucleotides on mesenteric lymph node T
      cell functional disturbances encountered after burn injury in rats. DESIGN: A
      prospective animal study. SETTING: University medical center research laboratory.
      SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats received a 30%,
      total body surface, full-thickness burn. Burn-injury rats received the IMPACT
      diet supplemented with glutamine, arginine, fish oil, and nucleotides or
      arginine, fish oil, and nucleotides, or an isocaloric/isonitrogenous diet without
      supplementation with glutamine, arginine, fish oil, or nucleotides. MEASUREMENTS
      AND MAIN RESULTS: Two days after injury, we found a significant decrease in the
      proliferation and interleukin-2 production by mesenteric lymph node T cells
      derived from rats fed on conventional chow compared with sham rats. The burn
      related suppression of mesenteric lymph node T-cell proliferation and interleukin
      2 production was prevented when the rats were fed on a high-protein diet rich in
      glutamine, arginine, fish oil, and nucleotides. We found that the
      immunostimulatory effects of the enriched diet are dependent on the presence of
      glutamine, arginine, fish oil, and nucleotides as feeding of rats on the
      isocaloric/isonitrogenous diet deficient in glutamine, arginine, fish oil, and
      nucleotides did not prevent the burn-related suppression of mesenteric lymph node
      T-cell dysfunction. Finally, our studies suggested that immunostimulatory effects
      of the diet are mediated by prostaglandin E(2) regulation of T-cell activation
      signaling molecule P59fyn. CONCLUSION: These results suggest that a diet rich in
      arginine, fish oil, and nucleotides, with and without glutamine, can effectively
      prevent T-cell dysfunction encountered after burn injury.

PMID- 12794419
TI  - Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier
      infusion in canine hypovolemic shock: a dose-response study.
AB  - OBJECTIVE: To compare effects of 6% hetastarch (Hextend) and hemoglobin-based
      oxygen carrier hemoglobin glutamer-200 (Hb-200) (bovine; Oxyglobin) on
      hemodynamics, arterial oxygen content, and systemic oxygen delivery in a canine
      hemorrhagic shock model. DESIGN: Randomized laboratory investigation. SETTING:
      University surgical research facility. SUBJECTS: Twenty-four anesthetized
      healthy, adult, mongrel dogs (28 +/- 1 kg; 7 female, 17 male). INTERVENTIONS:
      Dogs were instrumented for determinations of heart rate, arterial, central
      venous, pulmonary arterial, and pulmonary arterial occlusion pressures, and
      cardiac index. Total solids, colloid oncotic pressure, arterial oxygen content,
      Hb, lactate, pH, and blood gases were analyzed in blood samples. Recordings were
      made before, after 1 hr of hemorrhagic shock, and immediately and 3 hrs after
      infusion of either 30 mL/kg hetastarch (group 1), 10 mL/kg Hb-200 + 20 mL/kg
      hetastarch (group 2), 20 mL/kg Hb-200 + 10 mL/kg hetastarch (group 3), or 30
      mL/kg Hb-200 (group 4). MEASUREMENTS AND MAIN RESULTS: Hemorrhage (35 +/- 1
      mL/kg) reduced mean arterial pressure to 50 mm Hg and caused significant
      decreases in total Hb, mean pulmonary arterial pressure, cardiac index and
      systemic oxygen delivery, increases in heart rate and systemic vascular
      resistance, and lactic acidosis. In group 1, hetastarch infusion was accompanied
      by increases of pulmonary arterial pressure, cardiac index, and blood oxygen
      extraction above baseline, and decreases of systemic vascular resistance, total
      Hb, total solids, arterial oxygen content, and systemic oxygen delivery below
      baseline (p <.05). Other data returned to baseline. In groups 2 to 4, hemodynamic
      functions (except pulmonary arterial pressure) recovered, yet neither total Hb
      (i.e., plasma and red blood cell Hb) nor arterial oxygen content increased
      despite increases in plasma Hb of 2 to 5 g/dL and proportionate increases in
      total solids. Systemic oxygen delivery improved dose-dependently with Hb-200 but
      did not return to baseline (p <.05), reaching values comparable to hetastarch
      group only at 30 mL/kg Hb-200. In all groups, oxygen extraction remained above
      baseline. Metabolic acidosis and lactatemia resolved significantly faster in
      groups 2 to 4, and colloid oncotic pressure after resuscitation was greater in
      groups 2 to 4 than in controls (p <.05). CONCLUSIONS: In hemorrhagic shock, Hb
      200 infusion may not improve oxygen delivery more than hetastarch, likely due to
      hemodilution caused by its high colloid oncotic pressure, but may facilitate
      diffusive oxygen transport to tissues.

PMID- 12794420
TI  - Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early
      circulatory depression in porcine endotoxemia.
AB  - OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response
      with the microdialysis technique during porcine endotoxemia and to simultaneously
      monitor systemic hemodynamics. DESIGN: Prospective, randomized, placebo
      controlled trial with parallel groups. SETTING: Animal research laboratory at the
      University Hospital of Uppsala, Sweden. SUBJECTS: Thirteen piglets aged 12-14 wks
      receiving general anesthesia. INTERVENTIONS: After thoracotomy and the insertion
      of microdialysis probes in standardized locations in the left ventricle of the
      heart and in the quadriceps muscle, seven pigs received a continuous infusion of
      endotoxin, initiating a severe endotoxemic shock. Six pigs received saline
      instead of endotoxin. MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid
      and pronounced elevation of a metabolite obtained from prostaglandin degradation,
      15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of
      cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls).
      Simultaneously, we observed a decrease in left ventricular stroke work index in
      the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not
      alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused
      increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p
      <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate,
      inosine, adenosine, and calcium were not significantly changed. CONCLUSION:
      Endotoxemia induced a myocardial COX-mediated inflammation without signs of
      ischemia. In parallel, a depletion of myocardial energy substrates and a
      deterioration in myocardial performance were seen.

PMID- 12794421
TI  - Progesterone administration after trauma and hemorrhagic shock improves
      cardiovascular responses.
AB  - OBJECTIVE: Studies have shown that female rats during the proestrus stage have
      significantly improved cell and organ functions after trauma-hemorrhage compared
      with male and ovariectomized females. This study investigated the hypothesis that
      progesterone can improve the depressed cardiovascular function in sex steroid
      deficient female rats (i.e., ovariectomized females) after trauma-hemorrhage and
      resuscitation. DESIGN: Prospective study. SETTING: University laboratory.
      SUBJECTS: Ovariectomized female Sprague-Dawley rats (weight, 250-300 g).
      INTERVENTIONS: Rats underwent a 5-cm midline laparotomy (i.e., soft-tissue
      trauma), were bled to a mean arterial pressure of 35 mm Hg for approximately 90
      mins, and were then resuscitated using Ringer's lactate. A single dose of
      progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously
      during resuscitation. MEASUREMENTS: At 20 hrs after trauma-hemorrhage or sham
      operation, cardiac output and heart performance and the circulating blood volume
      were assessed using the indocyanine green dilution technique and a left
      ventricular catheter. Furthermore, the binding activity of progesterone receptors
      in nuclear extracts of left ventricular tissue was determined. RESULTS: Cardiac
      output, heart performance, and circulating blood volume were significantly
      decreased in vehicle-treated animals after trauma-hemorrhage. Administration of
      progesterone significantly improved cardiac output and heart performance and
      increased the circulating blood volume. This was associated with an increased
      progesterone receptor activity in the left ventricular nuclear extracts.
      CONCLUSION: Because administration of progesterone after trauma-hemorrhage in sex
      steroid-deficient females improved cardiovascular responses, this hormone seems
      to be a useful adjunct for the treatment of cardiovascular depression in
      postmenopausal and ovariectomized female trauma patients.

PMID- 12794422
TI  - Acute phase modulation of systemic insulin-like growth factor-1 and its binding
      proteins after major burn injuries.
AB  - OBJECTIVES: To provide a detailed, sequential analysis of insulin-like growth
      factor-1 and its binding proteins in adults during the acute phase after a major
      burn injury. DESIGN: Descriptive, repeated measurements for quantitation and
      characterization of insulin-like growth factor-1 and its binding proteins in
      adult burn survivors. SETTING: Burn center in a university hospital. PATIENTS: A
      total of 17 severely burned (>15% total body-surface area burned) adult patients.
      INTERVENTIONS: Venous blood was collected twice a day for 10 days and
      centrifuged, and the sera were stored at -80 degrees C until analysis. A series
      of 340 serum samples were analyzed by radioimmunoassay to determine the
      circulating concentration of insulin-like growth factor-1 and its major binding
      proteins (insulin-like growth factor-binding protein), by Western ligand
      blotting. To better understand the changes seen in systemic insulin-like growth
      factor-binding protein-3 levels by Western ligand blotting, a proteolysis assay
      was performed. MEASUREMENTS AND MAIN RESULTS: Insulin-like growth factor-1 levels
      were reduced from day 0 and correlated with insulin-like growth factor-binding
      protein-1 and -2 (p <.01), but not insulin-like growth factor-binding protein-3
      and -4. Insulin-like growth factor-binding protein-3 was decreased relative to
      normal on day 0, declined further until day 3, and began recovering by day 6, but
      returned to only 35% of normal by day 10. Insulin-like growth factor-binding
      protein-1 and -2 were increased relative to normal and remained increased
      throughout the 10-day period. Insulin-like growth factor-binding protein-4
      concentrations, however, were similar to normal at day 1 but gradually increased
      over time. Burn serum incubated with recombinant human glycosylated iodine-125
      insulin-like growth factor-binding protein-3 did not demonstrate any proteolysis,
      although proteolysis of nonglycosylated iodine-125 insulin-like growth factor
      binding protein-3 reached levels of approximately 40%. CONCLUSIONS: Insulin-like
      growth factor-binding protein-3 proteolysis does not seem to be the mechanism by
      which systemic insulin-like growth factor-1 levels are reduced in major burn
      survivors. In vitro proteolysis of recombinant human glycosylated and
      nonglycosylated iodine-125 insulin-like growth factor-binding protein-3 does not
      reflect the in vivo situation in major burn survivors.

PMID- 12794423
TI  - Role of ubiquitin-proteasome pathway in skeletal muscle wasting in rats with
      endotoxemia.
AB  - OBJECTIVE: To investigate the mechanism of muscle protein breakdown under
      endotoxemia condition. DESIGN: Randomized, controlled, animal experiment in a
      hospital institute. SETTING: Experimental laboratory. INTERVENTION: Either saline
      or endotoxin (Escherichia coli O(55)B(5), 10 mg/kg) were administered into the
      peritoneal cavity in rats. MEASUREMENTS AND MAIN RESULTS: The rate of total
      protein breakdown was increased by 29% and 61% in extensor digitorum longus
      muscle at 2 hrs and 6 hrs, whereas the myofibrillar proteolytic rate was
      increased by 155%, 222%, and 40% at 2 hrs, 6 hrs, and 12 hrs, respectively, in
      the endotoxin treatment group compared with that of the pair-fed normal control
      group. Meanwhile, compared with the normal control group, the level of 2.4
      kilobase (kb) messenger RNA (mRNA) for ubiquitin in extensor digitorum longus
      muscle in rats was increased by 153% and 470% at 2 hrs and 6 hrs. There were 87%
      and 117% increases in 1.2-kb mRNA for E2-14K, and 89% and 168% increase in RC2
      mRNA expression in extensor digitorum longus muscle in endotoxemic rats than
      normal control rats at 2 hrs and 6 hrs after injection of endotoxin peritoneally.
      The tumor necrosis factor-alpha and interleukin-6 concentrations in rat plasma
      progressively increased after endotoxin treatment, but tumor necrosis factor
      alpha peaked at the 2-hr time point, whereas interleukin-6 peaked at 12 hrs.
      Endotoxin administration resulted in a marked increase in endotoxin level at 2
      hrs and 6 hrs. No significant change was observed in soleus muscle after
      endotoxin injection. A significantly positive correlation was found between the
      net release of 3-methylhistidine and respective values of endotoxin, intensity of
      mRNA expression of 2.-kb ubiquitin, 1.2-kb E2-14K, and subunit RC2 in extensor
      digitorum longus muscle (r =.9882, .9731, .9653, .9814, p <.05). However, no
      significant correlation was seen between tumor necrosis factor-alpha or
      interleukin-6 and respective values of 3-methylhistidine, mRNA expression of 2.4
      kb ubiquitin, 1.2-kb E2-14K, and subunit RC2 (r =.3580, .4521, .5277, .4931, p
      >.05; r =.3950, .1767, .2136, .2519, p >.05, respectively.) in soleus muscle.
      CONCLUSIONS: Endotoxemia can induce enhancement of skeletal muscle protein
      breakdown, mainly involving myofibrillar protein and white, fast-twitch extensor
      digitorum longus muscle. Ubiquitin-proteasome proteolytic pathway plays an
      important and major role in skeletal muscle proteolysis. Endotoxin, tumor
      necrosis factor-alpha, and interleukin-6 can directly or indirectly regulate
      muscle protein breakdown.

PMID- 12794424
TI  - Modulation of tissue Toll-like receptor 2 and 4 during the early phases of
      polymicrobial sepsis correlates with mortality.
AB  - OBJECTIVE: To determine whether there was a correlation between induction of
      polymicrobial sepsis, modulation of tissue Toll-like receptor (TLR) gene, and
      protein expression and survival outcome. DESIGN: Prospective, randomized animal
      study. SETTING: University medical school research laboratory. SUBJECTS: Age- and
      weight-matched ICR/HSD mice. INTERVENTIONS: Sepsis was induced by cecal ligation
      and puncture (CLP). No-surgery and sham (laparotomy)-operated mice were controls.
      We also examined tissue TLR2 and TLR4 messenger RNA and TLR4 protein levels in
      mice treated with an immunomodulator that increases survival in polymicrobial
      sepsis. In the immunomodulator study, mice were treated with glucan phosphate (50
      mg/kg, intraperitoneally) 1 hr before CLP. No-surgery, sham surgery, glucan + no
      surgery, sham surgery + glucan, and CLP groups were employed as controls.
      MEASUREMENTS AND MAIN RESULTS: Total RNA was isolated from liver, lung, and
      spleen at 0, 1, 3, 6, 8, and 24 hrs after CLP. TLR gene expression was assessed
      by reverse transcription-polymerase chain reaction. Tissue TLR4 protein levels
      were evaluated at 24 hrs by Western blot and immunohistochemistry. CLP sepsis
      increased (p <.05) liver and lung TLR2 and TLR4 gene expression compared with
      controls. TLR4 protein concentrations also were increased. Increased TLR2/4 gene
      and TLR4 protein expression correlated with mortality. Immunoprophylaxis with
      glucan phosphate increased (p <.001) long-term survival (20% vs. 70%) but
      inhibited (p <.05) CLP-induced increases in tissue TLR2 and TLR4 messenger RNA
      expression as well as TLR4 protein expression. CONCLUSIONS: Early increases in
      TLR2/4 gene and TLR4 protein expression correlated with mortality, whereas
      blunting TLR gene and protein expression correlated with improved long-term
      survival. This suggests that early up-regulation of tissue TLR2/4 may play a role
      in the proinflammatory response and pathophysiology of polymicrobial sepsis.

PMID- 12794425
TI  - Stroke volumes and end-tidal carbon dioxide generated by precordial compression
      during ventricular fibrillation.
AB  - OBJECTIVE: The objective of this study was to measure stroke volumes produced by
      precordial compression during cardiopulmonary resuscitation and to quantitate
      relationships of stroke volume to measurements of end-tidal carbon dioxide.
      DESIGN: A prospective, observational animal study. SETTING: Medical research
      laboratory in a university-affiliated research and educational foundation.
      SUBJECTS: Domestic pigs. INTERVENTIONS: Eighteen anesthetized male, domestic pigs
      weighing between 40 and 45 kg were investigated. Ventricular fibrillation was
      electrically induced and continued for intervals ranging from 4 to 10 mins.
      Precordial compression was maintained at 80 per minute together with mechanical
      ventilation after endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Stroke
      volumes were measured with the aid of transesophageal echocardiographic imaging.
      End-tidal carbon dioxide was quantitated with conventional capnography. Baseline
      values of thermodilution cardiac output were highly correlated with
      echocardiographic measurements (r =.92). The stroke volume index produced by
      precordial compression averaged 0.45 mL/kg or approximately 37% of the average
      prearrest value of 1.22 mL/kg. The end-tidal carbon dioxide was highly predictive
      of stroke volume index (r =.88, p <.001) with a mean bias of 0.003 mL/kg.
      CONCLUSIONS: We confirmed that precordial compression produces approximately one
      third of prearrest stroke volumes during cardiopulmonary resuscitation and
      demonstrated that end-tidal carbon dioxide was quantitatively predictive of
      stroke volume index estimated by transesophageal echocardiographic imaging.

PMID- 12794426
TI  - Resuscitation with polyethylene glycol-modified human hemoglobin improves
      microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in
      awake hamsters.
AB  - OBJECTIVE: To determine whether resuscitation with polyethylene glycol-modified
      human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4
      g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of
      5.5 mm Hg, improves systemic and microvascular variables after hemorrhage
      compared with shed blood (SB) and 5% hydroxyethyl starch (HES). SETTING:
      Laboratory. SUBJECTS: Golden Syrian hamsters. DESIGN: Prospective study.
      INTERVENTIONS: Hamsters implemented with a skin fold chamber were hemorrhaged 50%
      of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG
      Hb). MEASUREMENTS AND MAIN RESULTS: Shock and resuscitation were monitored for 1
      hr each. Microvascular events were characterized in terms of vessel diameter,
      flow velocity, functional capillary density, and Po(2) in arterioles, venules,
      and extravascular tissue. Systemic variables include mean arterial pressure,
      heart rate, Po(2), Pco(2), pH, and base excess. MalPEG-Hb resuscitation increased
      functional capillary density to 64% vs. 44% for SB and 32% for HES relative to
      baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to
      baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin
      concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9
      g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po(2) of
      19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9
      g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in
      the tissue analyzed compared with SB. These measurements correlate well with a
      systemic indicator of recovery, base excess, 5.4 +/- 4.7 (MalPEG-Hb), 1.7 +/- 3.8
      (SB), and -0.3 +/- 5.7 (HES). CONCLUSION: The presence of 0.9 g/dL of high oxygen
      affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during
      shock to a significantly greater extent than that attainable with blood or HES.

PMID- 12794427
TI  - Prone position in subarachnoid hemorrhage patients with acute respiratory
      distress syndrome: effects on cerebral tissue oxygenation and intracranial
      pressure.
AB  - OBJECTIVE: To analyze the effect of prone position on cerebral perfusion pressure
      and brain tissue oxygen partial pressure in subarachnoid hemorrhage patients with
      acute respiratory distress syndrome (ARDS). DESIGN: Clinical study with
      retrospective data analysis. SETTING: Neurosurgical intensive care unit of a
      primary level university hospital. PATIENTS: Sixteen patients treated for
      intracranial aneurysm rupture with initial Hunt and Hess grade III or worse who
      developed ARDS within 2 wks after the bleeding. INTERVENTIONS: Routine
      neurosurgical intensive care treatment for subarachnoid hemorrhage and
      posthemorrhagic vasospasm including cerebral monitoring with continuous
      intracranial pressure and brain tissue oxygen partial pressure recordings.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial oxygenation, ventilatory
      setting, intracranial pressure, cerebral perfusion pressure, and brain tissue
      oxygen partial pressure in the supine as well as in the prone position were
      analyzed and compared. A significant increase in Pao(2) from 97.3 +/- 20.7 torr
      (mean +/- sd) in the supine position to 126.6 +/- 31.7 torr in the prone position
      was joined by a significant increase in brain tissue oxygen partial pressure from
      26.8 +/- 10.9 torr to 31.6 +/- 12.2 torr (both p <.0001), whereas intracranial
      pressure increased from 9.3 +/- 5.2 mm Hg to 14.8 +/- 6.7 mm Hg and cerebral
      perfusion pressure decreased from 73.0 +/- 10.5 mm Hg to 67.7 +/- 10.7 mm Hg
      (both p <.0001). CONCLUSIONS: The beneficial effect of prone positioning on
      cerebral tissue oxygenation by increasing arterial oxygenation appears to
      outweigh the expected adverse effect of prone positioning on cerebral tissue
      oxygenation by decreasing cerebral perfusion pressure in ARDS patients.

PMID- 12794428
TI  - Activation of protein C following infusion of protein C concentrate in children
      with severe meningococcal sepsis and purpura fulminans: a randomized, double
      blinded, placebo-controlled, dose-finding study.
AB  - BACKGROUND: Meningococcal septic shock in children results in high mortality and
      morbidity, and decreased protein C levels in these patients are associated with a
      poor outcome. We carried out a randomized, double-blinded, placebo-controlled
      study by supplying protein C concentrate. This phase 2 study was designed to
      assess the activation process of protein C and to study the dosing regimen of
      protein C concentrate in children with purpura fulminans and meningococcal septic
      shock in the perspective of a possible phase 3 trial. METHODS: Forty children
      were randomized to receive placebo or protein C concentrate (200 IU/kg, 400
      IU/kg, or 600 IU/kg), for a maximum of 7 days. Clinical and laboratory data,
      including plasma levels of protein C and activated protein C (APC), were
      collected at various time points. All patients received standard therapy for
      septic shock, including antibiotics, inotropic/vasoactive drugs, and blood
      products. RESULTS: Increased APC levels relative to baseline were observed for
      the 27 of 28 patients treated with protein C concentrate, and the areas under the
      curve of protein C and APC were correlated with the dosage of protein C
      concentrate administered. Activation of coagulation, as evidenced by d-dimer
      levels, as well as the ratio of thrombin vs. APC normalized significantly faster
      with increasing dosages of protein C concentrate. No adverse reactions related to
      protein C concentrate were observed. Nine of the 40 (23%) patients died, and five
      survivors required amputations, with no differences in these rates among the
      randomized groups. Baseline APC levels were positively correlated with sequential
      organ failure assessment and pediatric risk of mortality scores and with d
      dimers, tumor necrosis factor-alpha, interleukin-1, interleukin-6, interleukin-8,
      plasminogen activator inhibitor-1, TAT complexes, and PAP complexes. CONCLUSIONS:
      Treatment with protein C concentrate is safe in children with purpura fulminans
      and meningococcal septic shock and leads to dose-related increases of plasma APC
      and resolution of coagulation imbalances.

PMID- 12794429
TI  - Effect of human immunodeficiency virus on intensive care unit outcome of patients
      with Guillain-Barre syndrome.
AB  - OBJECTIVES: The primary objective of this study was to investigate the effect of
      human immunodeficiency virus (HIV) infection on the outcome of patients admitted
      to the intensive care unit (ICU) with severe Guillain-Barre syndrome (GBS)
      requiring mechanical ventilation. A secondary objective was to compare the
      clinical and laboratory features of HIV-seronegative and HIV-seropositive
      patients admitted to the ICU with severe GBS. DESIGN: Retrospective chart review.
      SETTING: Two tertiary, academic hospitals in Johannesburg, South Africa.
      MATERIALS AND METHODS: The case records of all patients admitted to the ICU with
      GBS between January 1995 and June 2002 were reviewed. Patients were included if
      their HIV status was known and if they had clinical features, electrophysiologic
      studies, and cerebrospinal fluid analyses consistent with GBS. Demographic data,
      days in ICU, days ventilated, CD4 T-lymphocyte counts (in the HIV group),
      cerebrospinal studies, infection rate, and mortality data were analyzed. RESULTS:
      A total of 13 patients met the inclusion criteria: seven were HIV seronegative
      and six were HIV seropositive. The median age in the HIV group was 34.5 yrs,
      compared with 47 yrs in the non-HIV group. There was no significant difference
      between the two groups in days spent in the ICU or days ventilated. There were no
      significant differences in cerebrospinal studies, electrophysiologic studies, and
      blood culture-positive infections between the two groups. All patients received
      intravenous immunoglobulin (0.4 g/kg/day for 5 days). There was one death in the
      HIV-seropositive group and no deaths in the HIV-seronegative group. The median
      CD4 T-lymphocyte count in the HIV group was 322.5 x 106 cells/L. CONCLUSION: HIV
      is commonly associated with GBS in South Africa. The ICU outcome in patients with
      HIV-associated GBS is similar to HIV-seronegative patients, particularly if the
      CD4 T-lymphocyte count is greater than 200 x 106 cells/L at admission.

PMID- 12794430
TI  - Cocaine and the critical care challenge.
AB  - OBJECTIVE: Cocaine, which first made its appearance >1,000 yrs ago, is now widely
      used throughout the world. The physiologic responses to cocaine may cause severe
      pathologic effects. This review highlights the many critical care challenges
      resulting from these effects. DESIGN: Historical vignettes, epidemiologic
      factors, modes of preparation and delivery, and the physiologic and pharmacologic
      effects of these agents are presented. SETTING: Cocaine causes intense
      vasoconstriction, which potentially causes damage to all organ systems. Examples
      of these toxicities are presented. PATIENTS: The adverse multisystem responses to
      cocaine exposure produce organ failure, which challenges diagnostic accuracy and
      therapeutic intervention. Organ system failure involves the brain, heart, lung,
      kidneys, gastrointestinal tract, musculature, and other organs. These harmful
      effects are additive to preexisting organ dysfunction. INTERVENTION: Recognition
      of associated cocaine injury alerts the physician that organ dysfunction is more
      likely to occur and to be more severe. Such anticipation helps plan for therapy
      in the critical care setting. RESULTS AND CONCLUSIONS: Cocaine use is an
      expanding health hazard, despite intense governmental efforts to contain its
      distribution and use. Recognition of the signs and symptoms of cocaine toxicity
      help anticipate the subsequent organ dysfunction and implement earlier organ
      system support.

PMID- 12794431
TI  - Acute lung injury: is the intensive care unit the tip of the iceberg?

PMID- 12794432
TI  - Platelet activating factor inhibition in sepsis: the end?

PMID- 12794433
TI  - Organizational effectiveness and patient outcomes in neonatal intensive care
      units.

PMID- 12794434
TI  - Intestinal epithelial regenerative capacity: an "Achilles' heel" in
      trauma/burn/sepsis injuries?

PMID- 12794435
TI  - Epinephrine in septic shock: Dr. Jekyll or Mr. Hyde?

PMID- 12794436
TI  - Time for a consensus definition of corticosteroid insufficiency in critically ill
      patients.

PMID- 12794437
TI  - Genomics and critical care: do the right thing!

PMID- 12794438
TI  - Continuous positive airway pressure, shock therapy, and gastric mucosal
      oxygenation.

PMID- 12794439
TI  - End-of-life captivity of advance directives in the United States: challenges from
      a French study.

PMID- 12794440
TI  - Intensive care unit support of hematopoietic stem cell transplant recipients: a
      case for cautious optimism.

PMID- 12794441
TI  - Plasma exchange in multiple organ failure: changing gears in sepsis and organ
      failure.

PMID- 12794442
TI  - Limiting myocardial cell injury during cardiopulmonary bypass: are steroids the
      answer?

PMID- 12794443
TI  - Modulation of systemic insulin-like growth factor-1 and its binding proteins
      after major burn injuries.

PMID- 12794444
TI  - The Toll of sepsis: altered innate immunity in polymicrobial sepsis.

PMID- 12794445
TI  - Counterintuitive red blood cell substitute--polyethylene glycol-modified human
      hemoglobin.

PMID- 12794446
TI  - Subarachnoid hemorrhage: a multiple-organ system disease.

PMID- 12794447
TI  - Improved oxygenation in acute lung injury: albumin gain or fluid loss?

PMID- 12794448
TI  - Detecting a temperature change at 41 degrees C.

PMID- 12794449
TI  - ODM/CardioQ esophageal Doppler technology.

PMID- 12794450
TI  - Continuous renal replacement therapies: potential for fluid-side bacterial
      contamination?

PMID- 12794451
TI  - The use of the intensive care unit as an environment for minor procedures in
      noncritically ill children.

PMID- 12794453
TI  - Perceived functional impact of abnormal facial appearance.
AB  - Functional facial deformities are usually described as those that impair
      respiration, eating, hearing, or speech. Yet facial scars and cutaneous
      deformities have a significant negative effect on social functionality that has
      been poorly documented in the scientific literature. Insurance companies are
      declining payments for reconstructive surgical procedures for facial deformities
      caused by congenital disabilities and after cancer or trauma operations that do
      not affect mechanical facial activity. The purpose of this study was to establish
      a large, sample-based evaluation of the perceived social functioning,
      interpersonal characteristics, and employability indices for a range of facial
      appearances (normal and abnormal). Adult volunteer evaluators (n = 210) provided
      their subjective perceptions based on facial physical appearance, and an analysis
      of the consequences of facial deformity on parameters of preferential treatment
      was performed. A two-group comparative research design rated the differences
      among 10 examples of digitally altered facial photographs of actual patients
      among various age and ethnic groups with "normal" and "abnormal" congenital
      deformities or posttrauma scars. Photographs of adult patients with observable
      congenital and posttraumatic deformities (abnormal) were digitally retouched to
      eliminate the stigmatic defects (normal). The normal and abnormal photographs of
      identical patients were evaluated by the large sample study group on nine
      parameters of social functioning, such as honesty, employability, attractiveness,
      and effectiveness, using a visual analogue rating scale. Patients with abnormal
      facial characteristics were rated as significantly less honest (p = 0.007), less
      employable (p = 0.001), less trustworthy (p = 0.01), less optimistic (p = 0.001),
      less effective (p = 0.02), less capable (p = 0.002), less intelligent (p = 0.03),
      less popular (p = 0.001), and less attractive (p = 0.001) than were the same
      patients with normal facial appearances. Facial deformity caused by trauma,
      congenital disabilities, and postsurgical sequelae present with significant
      adverse functional consequences. Facial deformities have a significant negative
      effect on perceptions of social functionality, including employability, honesty,
      and trustworthiness. Adverse perceptions of patients with facial deformities
      occur regardless of sex, educational level, and age of evaluator.

PMID- 12794454
TI  - Three-dimensional lip morphometry in adults operated on for cleft lip and palate.
AB  - Measurements were taken from 18 patients operated on for cleft lip and palate,
      aged 19 to 27 years, and 162 control subjects matched for sex, age, and ethnic
      group. Nine soft-tissue landmarks on the lips were digitized by a three
      dimensional electromagnetic instrument. From the landmarks, several linear
      distances (mouth width, philtrum width, vermilion height of upper and lower lip,
      total vermilion height, total lip height), the interlabial angle, and some areas
      (vermilion of upper lip, vermilion of lower lip, total vermilion) and volumes
      (upper lip volume, lower lip volume, total lip volume) were calculated. Patient
      and reference data were compared by t tests and Watson-Williams tests. In the
      men, significant differences (p < 0.05) were found in width of the philtrum,
      height and area of the vermilion part of the upper lip, and total vermilion
      height and area (all larger in male patients than in controls). In the women,
      significant differences were found in the height and area of the vermilion part
      of the upper lip (larger in female patients than in controls), and in the height
      and area of the vermilion part of the lower lip (smaller in patients than in
      controls). In both sexes, the interlabial angle was smaller than in the reference
      population. In conclusion, the upper lip of adult patients operated on for cleft
      lip and palate differed from that of healthy controls of the same age, sex, and
      ethnic group. Surgical correction of cleft lip and palate failed to provide a
      completely normal appearance. The analysis pointed out those parts of the lips
      and mouth (in particular, the vermilion part of the upper lip) that differed the
      most from the norm. The method may be used to indicate to the surgeon and patient
      where additional procedures might be performed to approximate the morphologic
      characteristics of a reference population.

PMID- 12794452
TI  - Genetic susceptibility to dupuytren disease: association of Zf9 transcription
      factor gene.
AB  - Transforming growth factor beta 1 (TGF-beta 1) is a key fibrogenic cytokine that
      has been shown to stimulate fibroblast proliferation and extracellular matrix
      deposition and has been implicated in the pathogenesis of Dupuytren disease. Zf9
      is a transcription factor that increases TGF-beta 1 expression in tissue. The
      authors previously demonstrated a lack of association between common TGF-beta 1
      and TGF-beta 2 polymorphisms and Dupuytren disease. Therefore, Zf9 transcription
      factor represents an additional candidate susceptibility gene for investigating
      hereditary predisposition to Dupuytren disease. Dupuytren disease, or Dupuytren
      contracture, is a progressive and recurrent fibroproliferative disease of unknown
      etiology that affects the human hands. It is often a familial disorder affecting
      Northern European Caucasians. Genes implicated in the development of Dupuytren
      disease have not yet been found. Using a polymerase chain reaction-restriction
      fragment polymorphism method, the authors genotyped a novel single nucleotide
      polymorphism in the 3' untranslated region of the Zf9 gene. A case-control
      association study of 138 patients with Dupuytren disease versus 255 controls
      demonstrated a statistically significant difference in the genotype and allele
      frequencies between patients and controls for Zf9 gene polymorphism. Presence of
      the G allele versus the A allele is associated with an increased risk of
      developing Dupuytren disease (odds ratio, 1.9; 95 percent confidence interval,
      1.2 to 2.9). The authors believe this to be the first report of a positive
      genetic association study in Dupuytren disease using single nucleotide
      polymorphisms.

PMID- 12794455
TI  - Anthropometric measurements of the endoscopic eyebrow lift in the treatment of
      facial paralysis.
AB  - Endoscopic eyebrow lift was performed on 51 patients presenting with eyebrow
      ptosis due to facial paralysis. The resulting anthropometric measurements of
      eyebrow position were analyzed statistically to evaluate the effectiveness of
      this method. When preoperative eyebrow differences between the paralyzed and
      nonparalyzed sides were measured, the average difference at midpoint was 4.4 mm,
      and at the highest point, 4.6 mm. When the same points were measured
      postoperatively, the average difference at midpoint was 2.4 mm, and at the
      highest point, 2.3 mm. The difference in eyebrow height between the paralyzed and
      nonparalyzed sides correlated positively with age, both preoperatively and
      postoperatively. However, differences between preoperative and postoperative
      eyebrow height (which reflects the effectiveness of endoscopic eyebrow lift) at
      the highest point did not correlate with age and at the midpoint displayed a
      slightly negative correlation with age. These results suggest that endoscopic
      eyebrow lift is effective among young patients whose eyebrow ptosis is minor and
      is relatively ineffective among elderly patients whose eyebrow ptosis is severe.
      The conventional method of juxta-brow excision is indicated for elderly patients,
      for whom the operative scar is almost inconspicuous.

PMID- 12794456
TI  - Prefabricated galeal flap based on superficial temporal and posterior auricular
      vessels.
AB  - Scalp layers are widely used in reconstructive procedures. The authors used
      prefabricated galeal flaps based on the superficial temporal or postauricular
      vessels for ear, cheek, mandible, and cranium reconstructions in three cases. In
      case 1, synchronous beard and ear reconstructions were accomplished by using the
      temporoparietal and retroauricular flaps. In case 2, a buccomandibular defect was
      reconstructed by transposing the supra-auricular and retroauricular galea with
      prefabricated bone and skin. In case 3, an epidural hematoma in the left
      frontoparietal area was evacuated after a circular craniectomy. The harvested
      bone was not put back on the defect area but buried between the periosteal and
      galeal layers because of brain edema. These layers were raised as an
      osteogaleoperiosteal flap and transposed onto the defect area after 7 weeks. When
      used with a prefabrication method, scalp layers offer versatile options for
      repairing composite defects of the head region. A galeal flap based on the
      posterior auricular vessels is practical and reliable in reconstructive
      procedures. The authors suggest that this flap is an option in cases in which the
      temporoparietal fascia artery or the superficial temporal artery is not
      available. Prefabrication of the harvested cranial bone inside the adjacent
      tissues offers several advantages in that a viable bone is provided at the end of
      the procedure, intervention at a distant area is avoided, the graft is placed on
      osteogenic tissue (periosteum) that is also transposed onto the defect, and
      sophisticated procedures such as microsurgical techniques are not needed.

PMID- 12794457
TI  - Arterial anatomy of the lower lip: a cadaveric study.
AB  - The aim of the study was to investigate the arterial anatomy of the lower lip.
      The location, course, length, and diameter of the inferior labial artery and the
      sublabial artery were revealed by bilateral meticulous anatomic dissections in 14
      adult male preserved cadaver heads. Another cadaver head was used for silicone
      rubber injection to fill the regional arterial tree. The inferior labial artery
      was the main artery of the lower lip and in all cases branched off the facial
      artery. The mean length of the inferior labial artery was found to be 52.3 mm
      (range, 16 to 98 mm). The mean distance of the origin of the inferior labial
      artery from the labial commissura was 23.9 mm. The mean external diameter of the
      inferior labial artery at the origin was 1.2 mm. The sublabial artery was present
      in 10 (71 percent) of the cadavers. Mean measurements of this artery were 1 mm
      for diameter, 23.4 mm for length, and 27.6 mm for distance from the labial
      commissura. The sublabial artery may originate from the facial artery or the
      inferior labial artery. This study found that this region does not have a
      constant arterial distribution, the inferior labial artery and the sublabial
      artery (if it exists) can be in different locations unilaterally or bilaterally,
      and the diameter and the length may vary.

PMID- 12794458
TI  - The Danish Registry for Plastic Surgery of the Breast: establishment of a
      nationwide registry for prospective follow-up, quality assessment, and
      investigation of breast surgery.
AB  - Although numerous epidemiologic studies have examined the long-term safety of
      silicone breast implants during the past decade, there is a relative lack of
      surveillance data on short-term health effects and complications following
      cosmetic surgery of the breast. The Danish Registry for Plastic Surgery of the
      Breast, established in May of 1999, provides plastic surgeons with a nationwide
      system for the collection of preoperative, perioperative, and postoperative data
      on women undergoing breast implantation, breast reduction, or mastopexy. The
      purpose of the Registry is to examine short-term and, eventually, long-term local
      complications and possible health effects, and to contribute to an ongoing
      evaluation of surgical results and surveillance of the products. Furthermore, the
      Registry will allow the identification of new areas for research into cosmetic
      and reconstructive breast surgery. Women accepting registration in the Danish
      Registry for Plastic Surgery of the Breast complete a self-administered
      questionnaire focusing on medical history and demographic and behavioral factors.
      Preoperative blood samples are drawn for storage. Surgical data, postoperative
      results, and complications are registered following surgery and at postoperative
      visits. Currently, registration has been initiated at 24 private and public
      clinics, representing more than 80 percent of the plastic surgery clinics in
      Denmark. As of November of 2001, a total of 1472 women with breast implants and
      560 women with breast reduction were included in the Registry. These figures are
      expected to increase annually by 1000 women undergoing breast implantation and
      500 women undergoing breast reduction or mastopexy. The authors present their
      experience of establishing the first nationwide comprehensive clinical
      epidemiologic database and biological bank for cosmetic and reconstructive
      surgery procedures.

PMID- 12794459
TI  - The vertical mammaplasty: a reappraisal of the technique and its complications.
AB  - Since 1989, superior pedicle vertical scar mammaplasty as described by Lejour has
      been used in the authors' department as the only technique for breast reduction.
      From 1991 through 1994, a series of 170 consecutive patients (330 breasts)
      underwent an operation. In these patients, minor complications were observed in
      30 percent of the patients and major complications in 15 percent. Surgical
      revision for scar or volume corrections was necessary in 28 percent of the
      breasts, which seemed unacceptable. Therefore, the original technique was
      modified by decreasing the skin undermining and avoiding liposuction in the
      breast. Primary skin excision was performed in the submammary fold at the end of
      the operation if the skin could not be puckered adequately. This modified
      technique was used from 1996 through 1999 in 138 consecutive patients (227
      breasts). In the second series, minor complications were observed in 15 percent
      of the patients and major complications in 5 percent. However, the technical
      modifications did not significantly change the rate of secondary scar and volume
      corrections, which were still necessary in 22 percent of the breasts. In large
      breasts, the addition of a horizontal scar at the end of the operation did not
      change the rate of secondary revision, which however compares favorably with the
      figures obtained with the inverted T, superior pedicle mammaplasty.

PMID- 12794460
TI  - Extended approach to the vascular pedicle of the gracilis muscle flap: anatomical
      and clinical study.
AB  - Dissection of the proximal gracilis vascular pedicle proceeds in a dark tunnel
      like space deep to the adductor longus. With the application of a previously
      described technique for an extended approach to the lateral arm free flap, the
      authors describe a novel technique that improves observation and thus facilitates
      dissection of the proximal gracilis vascular pedicle. A retrospective review of
      data for 18 consecutive patients who underwent gracilis muscle free flap
      harvesting with this modified technique between March of 1999 and October of 2001
      was conducted, to assess flap viability and patient outcomes. A cadaveric
      dissection was also performed, to study the anatomical features of the region in
      depth and to test the proposed flap modification. After the standard incision has
      been made, the dominant pedicle is exposed on the medial aspect of the gracilis
      muscle, running in a fascial cleft between the adductor longus and the adductor
      magnus. Intramuscular branches to the adductor longus are divided. A space is
      bluntly created anterior and lateral to the adductor longus by separating the
      fibrous connections to the surrounding adductor and sartorius muscles on both
      sides of the vascular pedicle. The gracilis muscle is then divided and passed
      deep to the adductor longus, into this space. With this new position, the final
      dissection of the pedicle can easily be performed. The confluence of the venae
      comitantes is frequently encountered, providing a larger-caliber single vein for
      microvascular anastomosis. The ages of the patients ranged from 9 to 70 years.
      The majority (14 of 18 patients) had traumatic wounds. The free flap survival
      rate was 100 percent. One minor complication of a seroma at the donor site was
      observed. One major complication of venous thrombosis was detected on
      postoperative day 3, with complete flap salvage. No other complications were
      noted. This technique is safe and permits direct approach to and excellent
      observation of the proximal aspect of the gracilis pedicle, without the need for
      headlights or deep retractors. An additional benefit is the frequent finding of a
      single larger vein from the merging of the venae comitantes close to the deep
      femoral vessels.

PMID- 12794461
TI  - Carbon dioxide laser dermabrasion for giant congenital melanocytic nevi.
AB  - The management of giant congenital melanocytic nevi remains controversial. There
      is a balance to be achieved between minimizing the disfiguring appearance of
      these lesions, both before and after surgical treatment, and limiting the risk of
      malignant change. A series of seven patients who were treated in the same manner,
      with carbon dioxide laser dermabrasion, is presented. It has been 6 years since
      the first patient was treated in this way, and no cases of recurrence have been
      observed. This technique enables the removal of all or most of the pigmented
      lesion, with minimal scarring and without the need for disfiguring skin grafts.
      It has been well proved that there is an increased risk of malignant changes
      among patients with these lesions, although the amount of increased risk for the
      patient is not clear. Evidence from a review of the currently available
      literature is presented to indicate why this management method, at best, should
      decrease this risk and, at worst, should make no difference to the overall risk
      for individual patients.

PMID- 12794462
TI  - Reliability of a structured method of selecting abstracts for a plastic surgical
      scientific meeting.
AB  - There is no generally accepted method for assessing abstracts that are submitted
      for a medical scientific meeting. This article describes the development and
      prospective evaluation of such a method applied to the 220 abstracts submitted
      for the 2000 Annual Meeting of the European Association of Plastic Surgeons.
      Structured abstracts were evaluated in three categories: aesthetic surgery, basic
      research, and clinical study. Each anonymous abstract was assessed separately by
      10 reputable European plastic surgeons. These reviewers used a structured rating
      questionnaire which resulted in a score given by each reviewer to each abstract
      between -6 and +6. The scores of all 10 reviewers were added for each abstract,
      and the papers were accepted in each of the three categories on the basis of this
      abridged score. To evaluate the reliability of this structured method of
      selection, the interrater agreement among the reviewers was tested by means of
      kappa analysis and the Cronbach alpha coefficient. The kappa values for agreement
      among reviewers regarding acceptability of abstracts were low, but the alpha
      coefficient indicated an acceptable degree of reliability of the average
      reviewers' ratings for all categories. Using a structured questionnaire can be
      helpful in the objective assessment of abstracts for a scientific meeting and may
      facilitate comparison of abstracts. Meritocratic dichotomy of abstracts by the
      reviewers is advocated to further improve reliability of the rating. Even though
      reliability generally increases with the number of reviewers, the annual increase
      of submitted abstracts may necessitate a decrease in the number of reviewers for
      each abstract.

PMID- 12794463
TI  - Bone reconstruction of the lower extremity: complications and outcomes.
AB  - A study was performed to analyze the results and final outcomes of bone
      reconstruction of the lower extremity. Twenty-six patients presented with type
      IIIB open fractures, nine with type IIIC open fractures, and 15 with chronic
      osteomyelitis. Seven patients underwent primary amputation, and reconstruction
      was attempted for 43 patients. The mean bone defect size was 7.7 cm (range, 3 to
      20 cm). Bone reconstruction was achieved with conventional bone grafts in 16
      cases, in association with either local (13 cases) or free (three cases) flaps.
      Vascularized bone transfer was performed in 24 cases, with either osteocutaneous
      groin flaps (10 cases), soleus-fibula flaps (12 cases), or osteocutaneous lateral
      arm flaps (two cases). For three patients, bone reconstruction was performed with
      a technique that combines the induction of a membrane around a cement spacer with
      the use of an autologous cancellous bone graft. Infections were observed to be
      responsible for prolonged hospital stays and treatment failures. The cumulative
      rates of sepsis were 4.6 percent at 1 week after injury and 62.8 percent at 2
      months. Vascular complications were also related to infections and were
      responsible for four secondary amputations. One patient asked for secondary
      amputation because of a painful nonfunctional lower limb. Bone healing occurred
      in 37 of 43 cases, and the average time to union was 9.5 months, with an average
      of 8.7 procedures. The mean lengths of stay were 49 days for conventional bone
      grafts and 62 days for vascularized bone grafts. All of the 50 patients were able
      to walk, with an average time of 14 months. All of the patients with amputations
      underwent prosthetic rehabilitation. Patients mostly complained about the
      reconstructed limb (62.8 percent). Joint stiffness was present in 40 percent of
      the cases. Other long-term complications were pain (nine cases), lack of
      sensation (five cases), infection (five cases), and pseudarthrosis (one case).
      However, all of the patients with successful reconstructions preferred their
      salvaged leg to an amputation. Of 41 patients who were working before the injury,
      26 returned to work.

PMID- 12794464
TI  - Reconstruction of the weight-bearing surface of the foot with nonneurosensory
      free flaps.
AB  - Neurotized fasciocutaneous flaps and split-skin grafted muscle flaps are the most
      frequently used free flap alternatives for the reconstruction of weight-bearing
      surfaces of the foot. An objective comparison of the innate characteristics of
      these two flap types, with respect to long-term stability, has not been possible
      because sensory reinnervation in the fasciocutaneous flaps has been a confounding
      factor. This study compares nonsensate fasciocutaneous flaps (n = 9) with
      nonsensate split-skin grafted muscle flaps (n = 11), with mean follow-up periods
      of 34.3 and 31.3 months, respectively. Patients completed a form that included
      questions regarding degree of pain at the operative site, presence of ulcers,
      ability to wear normal shoes, employment status, and time spent standing on foot.
      Touch and deep sensation were evaluated with Semmes-Weinstein and vibration
      tests, respectively. Significantly less pain and less ulceration (p < 0.05) were
      observed in the fasciocutaneous group. Semmes-Weinstein monofilament tests
      revealed poorer results with split-skin grafted muscle flaps, compared with
      fasciocutaneous flaps. These results indicate that even if the sensory protection
      of fasciocutaneous flaps is not considered, these flaps have superior properties,
      compared with split-skin grafted muscle flaps.

PMID- 12794465
TI  - Donor-site morbidity after free vascularized autogenous fibular transfer:
      subjective and quantitative analyses.
AB  - The purpose of this study was to determine the subjective and quantitative donor
      site morbidity after removal of a free vascularized fibula flap for
      autoreconstruction. Ten patients and six age-matched, healthy control subjects
      were included in this study. The postoperative periods ranged from 6 to 87
      months. Subjective donor-site morbidity was assessed with a patient questionnaire
      and the Enneking system. For quantification of donor-site morbidity, gait was
      evaluated during normal walking, walking under visual and cognitive constraints,
      and walking at a velocity higher than the preferred one. In general, the patient
      perception of donor-site morbidity was low. Complaints were frequently mentioned,
      however, including pain (60 percent), dysesthesia (50 percent), a feeling of
      ankle instability (30 percent), and inability to run (20 percent). Gait analyses
      revealed that patients walked at a lower preferred velocity, compared with
      control subjects. Furthermore, they demonstrated significant increases in the
      coefficients of variation of stride time during walking under visual and
      cognitive loads and during walking at a velocity higher than the preferred one,
      compared with normal walking. These increases were not observed for control
      subjects. These findings suggest that the reautomatization of gait is affected
      among patients. This study demonstrates that fibula harvesting is associated with
      low subjective morbidity but frequent complaints. Walking during complex tasks
      and at high velocities reveals that restoration of gait is not complete after
      partial fibulectomy.

PMID- 12794466
TI  - An alternative method to minimize pain in the split-thickness skin graft donor
      site.
AB  - In the art of plastic surgery, the reconstruction of tissue defects to obtain
      cosmetic and functional recovery is the major concern. Skin grafting is the most
      frequently used procedure for reconstructing defects of various size and
      anatomical localizations. On the other hand, donor-site problems associated with
      this invaluable procedure are inevitable. Various methods are used in the
      postoperative management of the partial-thickness donor site created during the
      harvest of a split-thickness skin graft. Each technique has the potential for
      complications of fluid loss, excessive pain, prolonged period of healing and
      immobilization, hypertrophic scarring, and undesirable pigmentation. Donor-site
      pain is probably the most disturbing complication in the early postoperative
      period. The aim of this article is to point out the significance of donor-site
      pain, which has not been emphasized thoroughly in the literature, and to
      introduce flap skin as a potential graft donor site for patients in whom
      reduction of donor-site morbidity is of primary concern. The principal goal of
      the technique described in this article is to eliminate donor-site pain by
      harvesting the graft from the flap that is insensate after the elevation. In 15
      patients, the overlying skin of the flap that had been used for reconstructive
      purposes was used as the donor site (group I). In the remaining 23 patients, the
      posterolateral thigh was used as the donor site (group II). Donor-site discomfort
      was recorded during the first 8 days postoperatively using a visual analogue
      scale. To analyze the data, we used the Friedman test, Dunn's multiple comparison
      test, and Mann-Whitney U test. It was observed that the visual analogue scale of
      both of the groups showed a significant decrease within days (group I, p <
      0.0001; group II, p < 0.0001). The mean pain scores were significantly lower in
      group I than in group II (p < 0.0001). When donor-site pain is of primary
      concern, this procedure provides uneventful and comfortable healing while
      avoiding postoperative pain in the donor site. For that reason, this technique
      might be used in appropriate cases to minimize donor-site pain.

PMID- 12794467
TI  - Neovaginal construction with buccal mucosal grafts.
AB  - Several surgical techniques have been designed to construct a neovagina that will
      be satisfying in appearance, function, and feeling when the vagina is
      congenitally absent. However, no method has yet been approved as a perfect
      solution. With the aim of solving the problems with conventional methods, the
      authors describe a new surgical technique that is simple and safe for treating
      vaginal agenesis. This technique consists of creating a mucosal lining of the
      neovaginal cavity using multiple full-thickness buccal mucosal patch grafts. Four
      patients with congenital absence of the vagina treated with this technique are
      presented. This surgical procedure created a mucus-providing lining inside the
      neovagina. Selecting the donor site in the oral region resulted in an
      inconspicuous donor-site scar. Histologically, the neovaginal lining was
      confirmed as mucosal, and the cream-colored viscous fluid found in the neovaginal
      cavity was confirmed as mucus. At a mean follow-up period of 15 months, the
      neovagina remained adequate in depth and width. All of the patients were
      interviewed to evaluate the function of the neovagina. Each patient reported
      having regular sexual intercourse and that the neovagina had felt normal to their
      partners. The encouraging results obtained in four cases suggest that this new
      technique deserves further application.

PMID- 12794468
TI  - The use of end-to-side nerve grafts to reinnervate the paralyzed orbicularis
      oculi muscle.
AB  - Facial paralysis is a serious neurologic disorder, particularly when it affects
      the eye. Loss of the protective blink reflex may lead to corneal ulceration and,
      possibly, visual loss. The purpose of this study was to compare different nerve
      grafting techniques to reanimate the paralyzed eyelid. Sixteen adult dogs (25 kg
      each) were allocated into four groups. Denervation of the left hemi-face was
      performed in all cases. One dog served as a control animal (group I). Group II
      dogs (n = 5) underwent end-to-side coaptation of the nerve graft to the intact
      palpebral branch and end-to-end coaptation to the denervated palpebral branch.
      Group III dogs (n = 5) underwent end-to-end coaptation of the nerve graft to the
      intact palpebral branch and end-to-end coaptation to the denervated palpebral
      branch. Group IV dogs (n = 5) underwent end-to-side coaptation of the nerve graft
      to the intact and denervated palpebral branches. The animals were monitored for 9
      months after the surgical procedures, to allow adequate time for reinnervation.
      The dogs were postoperatively monitored with clinical observation,
      electrophysiologic testing, video motion analysis, and histologic assessments.
      Clinical observation and electrophysiologic testing demonstrated the production
      of an eye blink in the denervated hemi-face in all experimental groups. There was
      a trend toward increased speed of reinnervation for group III animals (end-to-end
      coaptations). It was concluded that end-to-side coaptation can produce a
      contralateral synchronous eye blink in a clinically relevant, large-animal model.

PMID- 12794469
TI  - Effect of various nerve decompression procedures on the functions of distal limbs
      in streptozotocin-induced diabetic rats: further optimism in diabetic neuropathy.
AB  - It is known that diabetic neuropathy is the result of endoneurial edema caused by
      various biochemical reactions triggered by hyperglycemia. This sequence of events
      can cause cessation of circulation at the perineurial level, or the tough layer,
      which is not resilient enough to spread intraneural pressure. Internal and
      external limiting structures create a double crush phenomenon to the nerve
      structure. Decompression of the nerve trunk at separate levels is one of the
      adjuncts to the overall treatment plan for diabetic neuropathy. In this study,
      the right sciatic nerves of 30 rats with streptozotocin-induced diabetes were
      used; three groups were created. In the control group, the sciatic nerves were
      explored and dissected only. In group II, tarsal tunnel release was performed and
      accompanied by epineurotomy of the sciatic nerve and its peroneal and tibial
      extensions. In group III, in addition to the procedures performed in group II,
      perineural sheaths, exposed through the epineurotomy sites at both the peroneal
      and tibial nerves, were incised for decompression of the fascicles. Improvement
      in diabetic neuropathy was evaluated by using footprint parameters. The last
      print length values, estimated according to the 38-month measurements, were 26.1
      +/- 0.12 mm in the control group, 23.2 +/- 0.07 mm in group II, and 22.2 +/- 0.1
      mm in group III. The toe spread and intermediate toe spread values of the groups
      were parallel to improvements in print lengths throughout the study. The best
      improvement was observed in the perineurotomy group. Finally, an electron
      microscopic study revealed variable degenerative changes in all groups, but they
      were milder in groups II and III. This experimental study reveals that adding
      internal decompression to external release doubled the effect in reducing
      derangement in the sciatic nerves of the rats and, in the authors' opinion,
      offers cause for further optimism in the treatment of diabetic neuropathy.

PMID- 12794470
TI  - Scarless fetal wounds are associated with an increased matrix metalloproteinase
      to-tissue-derived inhibitor of metalloproteinase ratio.
AB  - In contrast to adult cutaneous wounds, early fetal wounds heal scarlessly. Fetal
      rat skin transitions from scarless repair to healing, with scar formation between
      days 16.5 (E16) and 18.5 (E18) of gestation. Term gestation is 21.5 days. The
      composition of the extracellular matrix in fetal skin and wounds differs from
      that of the adult. Matrix metalloproteinases (MMPs) and their tissue-derived
      inhibitors (TIMPs) determine the architecture of the extracellular matrix. The
      authors hypothesized that differential expression of MMPs and TIMPs occurs during
      the ontogenetic transition to scar-forming repair in fetal skin and wounds. Full
      thickness, excisional wounds (2 mm) were created on the dorsum of E16 (n = 42
      fetuses) and E19 fetal rats (n = 42 fetuses). Wounds were harvested at 24, 48,
      and 72 hours. Nonwounded skin from littermates was also harvested as controls.
      Six E16 and E19 wounds were fixed 72 hours after injury, stained with hematoxylin
      and eosin, and examined by light microscopy. RNA was isolated from the remaining
      wounds and skin, and a reduced-cycle, primer-specific, reverse-transcriptase
      polymerase chain reaction was performed to semiquantitatively determine relative
      gene expression of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14 and of TIMP-1, TIMP-2,
      and TIMP-3. Significance was determined by unpaired two-tailed t test (p < 0.05)
      and analysis of variance. In both E16 and E19 wounds, reepithelialization was
      complete by 72 hours. E16 wounds healed scarlessly, whereas E19 wounds healed
      with scar. During late gestation, skin expression of MMP-1 and MMP-14 (membrane
      type-1 MMP) doubled, whereas MMP-2 expression increased nearly 50-fold. Levels of
      MMP-7 and MMP-9 were unchanged in developing skin. As for the TIMPs, skin
      expression of TIMP-2 increased more than four-fold, whereas TIMP-1 and TIMP-3
      expression was unchanged. In both scarless and scarring wounds, up-regulation of
      MMP-1 and MMP-9 occurred. However, the maximal increase in MMP-1 and MMP-9
      expression occurred much more rapidly and was much greater in the scarless E16
      wounds (28-fold versus 23-fold for MMP-1 and 18-fold versus nine-fold for MMP-9).
      Unchanged in scarless wounds, MMP-2 levels decreased more than three-fold in
      scarring wounds. MMP-14 (membrane type-1 MMP) expression increased three-fold in
      scarless wounds but was unchanged in scarring wounds. In contrast, TIMP-1 and
      TIMP-3 expression in E19 scarring wounds increased six-fold and four-fold,
      respectively. MMP-7 and TIMP-2 expression did not change in response to injury.
      E16 scarless wounds have greater MMP relative to TIMP expression than E19
      scarring wounds. This favors extracellular matrix turnover, facilitates migration
      of fetal cells, and promotes scarless repair.

PMID- 12794471
TI  - Dehydroepiandrosterone protects the microcirculation of muscle flaps from
      ischemia-reperfusion injury by reducing the expression of adhesion molecules.
AB  - Adhesion molecules contribute to ischemia-reperfusion injury by increasing the
      endothelial adhesion and extravasation of leukocytes. Scientific evidence
      suggests that presurgical treatment with dehydroepiandrosterone may protect the
      microvasculature against this damage, but the exact mechanism is not known. The
      purpose of this study was to investigate the effects of presurgical
      dehydroepiandrosterone treatment on microcirculatory hemodynamic parameters and
      the expression of adhesion molecules in a rat cremaster muscle flap model. Twenty
      male rats were randomly assigned to three experimental groups. In group I (n =
      5), the muscle flaps did not receive presurgical treatment. In group II (n = 6),
      propylene glycol (30 mg/kg), the vehicle for dehydroepiandrosterone, was injected
      intravenously before ischemia was induced. In group III (n = 9),
      dehydroepiandrosterone (30 mg/kg) was injected intravenously before ischemia was
      induced. All flaps were subjected to 6 hours of ischemia and 90 minutes of
      reperfusion. Microcirculatory variables (functional capillary density, red blood
      cell velocity in the main flap arteriole, and numbers of rolling, sticking, and
      transmigrating leukocytes), blood levels of three adhesion molecules (L-selectin,
      Mac-1 integrin, and CD44), and the numbers of leukocytes expressing those
      molecules were analyzed. Analysis of the microcirculatory parameters revealed
      that dehydroepiandrosterone treatment before ischemia had significant
      preservative effects on the red blood cell velocity and functional capillary
      density 30 and 90 minutes after reperfusion, compared with the control and
      vehicle-treated groups. Leukocyte-endothelial cell interactions were also
      affected by dehydroepiandrosterone treatment, as reflected by significant
      decreases in the numbers of sticking and transmigrating leukocytes 30 and 90
      minutes after reperfusion. In dehydroepiandrosterone-treated animals, leukocytes
      exhibited lower levels of expression of adhesion molecules after the onset of
      ischemia, compared with the control groups. In this study, intravenous
      dehydroepiandrosterone administration reduced the activation of leukocytes and
      improved red blood cell velocity and capillary perfusion in the muscle flap
      microcirculation during ischemia-reperfusion injury. This protective effect was
      most likely the result of delayed expression of Mac-1 integrin, L-selectin, and
      CD44 molecules on leukocytes.

PMID- 12794472
TI  - Biodurability of retrieved silicone gel breast implants.
AB  - This study analyzed the shells of single-lumen silicone gel breast implants
      within the general context of device durability in vivo. The investigation
      included the major types of gel-filled implants that were manufactured in the
      United States in a 30-year period. The implants analyzed were Cronin seamed (two
      explants and one control), Silastic 0 and Silastic I (18 explants and seven
      controls), and Silastic II (22 explants and 43 controls). The biodurability of
      the explants was investigated with measurements of the mechanical and chemical
      properties of the various types of silicone gel control and explanted shells,
      with implantation times ranging from 3 months to 32 years. The shell properties
      measured for the controls and explants included the stress-strain relationships,
      tensile strength, elongation, tear resistance, moduli, cross-link density, and
      amount of extractable material in the shell. In addition, the mechanical
      properties of shells that had been extracted with hexane were analyzed for both
      explants and control implants. The silicone gel explants investigated in this
      study included some of the oldest explants of the various major types that have
      been tested to date. For assessment of long-term implantation effects, the data
      obtained in this study were combined with all known data from other institutions
      on the various major types of gel implants. The study also addressed the failure
      mechanisms associated with silicone gel breast implants. The results of the study
      demonstrated that silicone gel implants have remained intact for 32 years in vivo
      and that degradation of the shell mechanical and chemical properties is not a
      primary mechanism for silicone gel breast implant failure.

PMID- 12794473
TI  - The features of thrombus in a microvessel injury model and the antithrombotic
      efficacy of heparin, urokinase, and prostaglandin E1.
AB  - In failed flap transfers and in burn injuries, superoxides and thrombi generated
      in the microcirculation are considered responsible for tissue injury. A dynamic
      and morphologic analysis of thrombus formation was conducted in a model of
      microvessel injury, and an analysis was made of the different antithrombotic
      effects of heparin, urokinase, and prostaglandin E(1). The dye-light method was
      used (i.e., injury of the endothelium by reactive oxygen species) to induce
      thrombus formation in both the arterioles and venules of the rabbit ear chamber
      under an intravital microscope-television system. The dynamic course of thrombus
      formation was observed, and the period from irradiation to complete obstruction
      of blood flow (i.e., time to stasis) was measured and compared in relation to
      various treatment conditions. Arteriolar thrombi were formed by platelet
      aggregation. Venular thrombi were composed of platelets and erythrocytes that
      gathered and adhered around leukocytes stuck to the vessel wall. Heparin
      treatment prolonged the time to stasis in both the arterioles and the venules.
      Urokinase extended the time to stasis in the venules but not in the arterioles.
      Prostaglandin E(1)-treatment significantly prolonged the time to stasis in the
      arterioles, but only high-dose prostaglandin E(1) prolonged the time to stasis in
      the venules. The results of this study show that endothelial damage caused by
      superoxides promotes the formation of thrombi that differ in composition between
      the arteriole and the venule and that the effectiveness of each drug varies
      accordingly. The authors believe that these agents can be used with increased
      efficacy if the two types of thrombi and the specific antithrombotic effects of
      each agent are considered.

PMID- 12794474
TI  - Measurement in vivo of the survival rate in autologous adipocyte transplantation.
AB  - Up until now, research on fat cells has been unable to prove their survival rate
      objectively in vivo. In this article, the first application of the cell surface
      marker PKH26 in the fat cells of rats is reported. In a study of 48 Lewis rats,
      this method enabled the objective stereometry of viable and necrotic grafts after
      variable follow-up times in groups of eight animals each. The best survival rate
      was 30.41 percent, and the best implantation site was the interscapular subcutis.
      During follow-up, a characteristic change in size of the viable fat cells matched
      the in vitro findings of various investigators. Because of the surface marking,
      it could be proved that the viable cells found after 6 months were transplanted
      cells that had undergone a cycle of fat deprivation and regaining. This is proof
      of the cell survival theory postulated by Peer in 1950.

PMID- 12794475
TI  - Single-stage lip and nasal reconstruction in holoprosencephaly.

PMID- 12794476
TI  - Bitemporal ganglioglioma: surgical management of an unusual intracranial and
      extracranial tumor.

PMID- 12794477
TI  - Purse-string mastectomy with immediate prosthetic reconstruction: an improved
      skin-sparing technique for small breasts.

PMID- 12794478
TI  - Aesthetic and functional considerations of radical neck deformities.

PMID- 12794479
TI  - The external oblique turnover muscle flap.

PMID- 12794480
TI  - A novel method of skeletal fixation in an above-elbow replantation: the dowel pin
      technique.

PMID- 12794481
TI  - A single-stage operation in the treatment of chronic osteomyelitis of the lower
      extremity including reconstruction with free vascularized iliac bone graft and
      free-tissue transfer.

PMID- 12794482
TI  - Reverse-flow posterior interosseous artery flap revisited.

PMID- 12794483
TI  - Changes in facial movement and synkinesis with facial neuromuscular reeducation.

PMID- 12794484
TI  - Nail transfer: evolution of the reconstructive procedure.

PMID- 12794485
TI  - The history of otolaryngology in plastic surgery.

PMID- 12794486
TI  - The management of orbitozygomatic fractures.
AB  - Orbitozygomatic injuries are among the most common fractures encountered by the
      plastic surgeon. Appropriate management depends on an accurate diagnosis,
      focusing on the physical examination and data from computed tomography scans. One
      must pay particular attention to the orbital component of this injury, as it is
      from this that so much of the morbidity relating to these fractures is incurred.
      As with all facial fractures, accurate reduction is paramount to a successful
      outcome. As many buttresses as are necessary should be visualized to ensure an
      anatomic reduction. The amount and location of fixation depend on the fracture
      anatomy.A successful outcome may be expected if these basic principles are
      followed.

PMID- 12794487
TI  - Tort reform and state medical boards: an opportunity to enhance patient safety
      and promote the public trust.

PMID- 12794488
TI  - Morphometry of the adult human earlobe: a study of 547 subjects and clinical
      application.
AB  - The purpose of this study was to define the factors that influence earlobe length
      and to establish a standard for adult earlobe length by sex and age. The study
      sample consisted of 547 adult subjects older than 20 years of age. A randomized,
      prospective design was used. Patients with malignancies, previous surgery or
      trauma to the earlobe, or congenital earlobe anomalies were excluded. The
      following variables were studied: sex; age; ethnic origin; skin complexion;
      height, weight, and body mass index; and piercing. Pearson's correlation,
      analysis of variance, t test, and multiple regression analysis were used for the
      statistical analysis. There were 383 women (70 percent) and 164 men (30 percent)
      aged 20 to 80 years. The average length of the left earlobe was 1.97 cm (SD, 0.42
      cm), and that of the right earlobe, 2.01 cm (SD, 0.42 cm) (p < 0.0001). A post
      hoc test revealed a statistically significant difference among the three age
      groups (20 to 40 years, 40 to 60 years, and >60 years) in both men and women.
      Pendulous earlobes were significantly longer and less symmetrical than
      nonpendulous ones by t test. In men, nonpierced left earlobes were longer than
      pierced lobes; in women, there was no significant difference between pierced and
      nonpierced ears. Pearson's correlation tests for weight, height, and body mass
      index showed that only weight had a significant effect on earlobe length, and
      only in women. Analysis of variance for ethnic origin and skin color revealed a
      longer left earlobe in Ashkenazi and Sephardic Jews compared with Ethiopian,
      Asian, and American Jews and Arabs and a short earlobe in blacks compared with
      dark and fair-skinned people. On multiple regression analysis, sex and age were
      the only factors that contributed to earlobe length. A table of average earlobe
      length by age was formulated on the basis of the authors' findings. These data,
      together with the knowledge that earlobe length changes little in women over 40,
      that earlobes are not symmetrical, and that right and left nonpendulous earlobes
      are symmetrical in individual patients and shorter than pendulous earlobes, can
      assist the plastic surgeon in deciding on the proper time for loboplasty. The
      preferable technique is creating a nonpendulous earlobe to minimize the chances
      of further elongation with time.

PMID- 12794489
TI  - Reconstruction with irradiated homograft costal cartilage.
AB  - The authors present their experience with 51 patients who underwent 55
      reconstructive and cosmetic operative procedures with irradiated homograft costal
      cartilage, who were studied between August of 1988 and June of 2001. The
      procedures included 52 rhinoplasties and three penile implantations among a total
      of 130 grafts. Follow-up ranged from 7 months to 12 years. There were two
      immediate graft exposure complications. Late complications included displacement
      of the graft in two patients, fracture of the graft in one patient, and partial
      resorption in one patient at 6 months postoperatively. The experience is
      described and the literature is reviewed.

PMID- 12794490
TI  - Incidence of cervical branch injury with "marginal mandibular nerve pseudo
      paralysis" in patients undergoing face lift.
AB  - The anatomy of the cervical and marginal mandibular branches of the facial nerve
      is reviewed. In the senior author's practice, "pseudoparalysis of the marginal
      mandibular nerve" due to cervical branch injury occurred in 34 of 2002
      superficial musculoaponeurotic system-platysma face lifts (1.7 percent) and was
      associated with a full recovery in 100 percent of cases within a time period
      ranging from 3 weeks to 6 months. Cervical branch injury can be distinguished
      from marginal mandibular nerve injury by the fact that the patient will be able
      to evert the lower lip because of a functioning mentalis muscle.

PMID- 12794491
TI  - Efficacy of reconstituted and stored botulinum toxin type A: an
      electrophysiologic and visual study in the auricular muscle of the rabbit.
AB  - Once botulinum toxin type A is reconstituted, the manufacturer recommends that it
      be used in approximately 4 hours. As a result, a significant amount of this
      costly drug is often discarded because it is not completely used in the
      recommended period. The purpose of the present study was to compare fresh versus
      stored reconstituted botulinum toxin type A for (1) initial potency, (2) duration
      of action, and (3) bacterial colonization. Using a rabbit model, 20 New Zealand
      White rabbits were divided into four groups (I to IV). All rabbits had an
      injection of 2.5 U of reconstituted botulinum toxin into the right anterior
      auricular muscle. The first group was injected with botulinum toxin type A that
      was freshly reconstituted and served as the control. The second, third, and
      fourth groups were injected with botulinum toxin type A that had been
      reconstituted and stored for 2, 6, and 12 weeks, respectively, in a conventional
      freezer. Each rabbit had daily visual evaluation of the ear, with the position of
      auricle being graded from I to III. In addition, each rabbit had a nerve
      conduction study performed on the right anterior auricular muscle before
      injection and every 2 weeks after injection. Amplitude was chosen as the
      principal variable in the data analysis because it is the best predictor of
      physiologic changes at the muscle motor unit level. The endpoint of the study was
      defined as the time at which the nerve conduction studies and the visual
      inspections returned to baseline, preinjection levels. Botulinum toxin type A was
      also cultured before injection into each group.Overall, the nerve conduction data
      revealed a trend with a faster recovery (return to baseline) with the stored
      botulinum toxin. Groups IV and III returned to baseline first, followed by groups
      II and I. However, there was no significant difference among the groups at 2 and
      4 weeks after injection, indicating that initial potency was unchanged. The
      differences between the groups became significant (p < 0.05) at 6 weeks and
      onward, suggesting that the duration was affected. Group I (fresh botulinum
      toxin) and group II (toxin stored for 2 weeks) had comparable outcomes and were
      not significantly different at any time period. Under visual inspection, the mean
      recovery time for each group was as follows: group IV, 5.4 weeks; group III, 7.0
      weeks; group II, 6.75 weeks; and group I, 7.80 weeks. The results showed
      significance (p < 0.05) beginning after 3 weeks among some groups. Again, there
      was an overall quicker trend to return to baseline with the longer storage of the
      botulinum toxin (groups III and IV). These results support the authors'
      conduction study data, which suggest that the initial potency is not affected but
      the duration of action is. Again, groups I and II had comparable results.
      Microbiology cultures showed no growth of either aerobic or anaerobic bacteria at
      7 days. In conclusion, using the rabbit model, it seems that reconstituted and
      stored botulinum toxin type A has the same initial potency but the duration of
      action is affected sometime after 2 weeks of storage. No bacterial contamination
      was associated with storing unpreserved reconstituted botulinum toxin type A for
      up to 12 weeks.

PMID- 12794492
TI  - Immediate rupture of breast implant following trauma.

PMID- 12794493
TI  - Cutis laxa: clinical experience and outcomes.

PMID- 12794494
TI  - Face lifts and brow lift after radiotherapy.

PMID- 12794495
TI  - Caudal nasal deviation.
AB  - Caudal nasal deviation, manifested by a "crooked tip," asymmetric nostrils, and a
      deviated columella, is one of the most challenging deformities encountered in
      rhinoplasty. This entity is often ignored by rhinoplasty surgeons, on the basis
      of the assumption that correction of other segments of the deviated nose will
      improve the caudal nose. Failure to correct this imperfection (or, occasionally,
      deformity) invariably produces suboptimal results. The nasal structures involved
      in caudal nasal deviation, namely, the septum, the lower lateral cartilages, and
      the anterior nasal spine, must be evaluated for identification of the anatomical
      blocks that have a causative role in caudal nasal deviation. The specific
      structures with abnormalities related to this deformity are discussed, as are
      techniques for the correction of the deformities. These techniques significantly
      augment the surgeon's repertoire of methods for addressing the subtleties of
      caudal nasal deviation correction and achieving predictable results.

PMID- 12794496
TI  - An update on the lateral nasal osteotomy in rhinoplasty: an anatomic endoscopic
      comparison of the external versus the internal approach.

PMID- 12794498
TI  - Cryopreservation of adult stem cells derived from lipoaspirate.

PMID- 12794500
TI  - Continuous oblique mattress suture.

PMID- 12794499
TI  - First experiences with recombinant human bone morphogenetic protein 7 (osteogenic
      protein 1) in a human case in maxillofacial surgery.

PMID- 12794501
TI  - Hypothesis on a cause of temporomandibular joint disorders.

PMID- 12794503
TI  - The use of sterilized feminine hygiene sanitary napkins for dressing of skin
      grafted and donor areas.

PMID- 12794502
TI  - A pedicle forearm fillet flap aided by subperiosteal proximal dissection in
      shoulder disarticulation.

PMID- 12794504
TI  - True ulnar artery aneurysm of the hand in an 8-year-old boy.

PMID- 12794505
TI  - Root Z-epicanthoplasty in Asian eyelids.

PMID- 12794506
TI  - DIEP versus TRAM for breast reconstruction.

PMID- 12794507
TI  - Tram flap delay: two techniques and an unresolved question.

PMID- 12794508
TI  - Plastic surgery beyond the human genome.

PMID- 12794509
TI  - Management of pressure ulcers.

PMID- 12794510
TI  - Unusual branching of the lateral circumflex femoral arterial system for
      anterolateral thigh flaps.

PMID- 12794511
TI  - The surgical glove as a breast sizer.

PMID- 12794512
TI  - Pocket pc: an aid to clinical consultation.

PMID- 12794513
TI  - A cheap device to perform ultrasound-assisted lipoplasty.

PMID- 12794514
TI  - Yet another use of the face mask.

PMID- 12794515
TI  - The use of recombinant erythropoietin in the reduction of transfusion rates in
      craniosynostosis repair in infants and children.

PMID- 12794516
TI  - Henna skin reaction.

PMID- 12794517
TI  - Anatomic basis and technical aspects of a new brachial plexus avulsion injury
      model in the rat.

PMID- 12794519
TI  - Transplacental and other routes of cancer transmission between individuals.
AB  - Cancer in pregnancy is not rare, and the possibility of transmission of
      malignancy from mother to child, while infrequent, represents a clinical
      challenge for the primary pediatric hematologist-oncologist. The authors
      summarize all reported cases of vertically transmitted cancer and review other
      reported cases of person-to-person transfer of malignancy. As these cases
      represent a unique physiologic model of tumor transplantation, the biology of
      cancer transmission is discussed and provisional guidelines are given for the
      screening of infants born to women with cancer.

PMID- 12794520
TI  - Prophylactic use of myelopoietic growth factors in children after
      myelosuppressive chemotherapy: does it pay?

PMID- 12794521
TI  - Economic evaluation of recombinant human granulocyte colony-stimulating factor in
      very high-risk childhood acute lymphoblastic leukemia.
AB  - PURPOSE: In a previous randomized study, the authors reported that granulocyte
      colony-stimulating factor (G-CSF) increased the chemotherapy dose-intensity
      delivered during the consolidation therapy of high-risk childhood acute
      lymphoblastic leukemia (ALL). The aim of the current study was to perform an
      economic evaluation in the same cohort. METHODS: In this open-label multicenter
      randomized trial, prophylactic G-CSF was administered after consolidation therapy
      courses. Economic data were retrospectively quantified for each patient: hospital
      stays, drugs, and blood products. RESULTS: Sixty-seven children were enrolled in
      the very high-risk branch of the FRALLE 93 protocol. Chemotherapy dose-intensity
      was significantly increased (105 +/- 5% in the G-CSF group vs. 91 +/- 4% in the
      non-G-CSF group, P < 0.001). The mean total costs per child were not
      statistically different: 32,309 dollars in the G-CSF group versus 31,569 dollars
      in the non-G-CSF group. Further analysis per child and per course (R3 or COPADM)
      demonstrated that the mean cost of hospitalization and the mean cost of
      intravenous antibiotics were significantly decreased in the G-CSF group after R3
      courses (3,857 dollars vs. 4,993.80 dollars, P < 0.001; 171.40 dollars vs. 306.20
      dollars, P = 0.029, respectively), but the cost of platelet transfusion was
      significantly increased (P = 0.03). Conversely, post-COPADM costs were similar.
      Finally, mean costs per course in the two randomized groups were not
      significantly different: 5,848.80 dollars versus 6,181 dollars and 7,388.10
      dollars versus 6,475.70 dollars for R3 and COPADM, respectively. The 3-year
      probability of event-free survival between the two groups was not different.
      CONCLUSIONS: G-CSF can increase chemotherapy dose-intensity in very high-risk ALL
      without raising costs, but event-free survival was not improved. The cost benefit
      of prophylactic treatment by G-CSF relies on the chemotherapeutic regimen given
      prior to G-CSF administration.

PMID- 12794522
TI  - Long-term morbidity in children treated with fractionated high-dose-rate
      brachytherapy for soft tissue sarcomas.
AB  - BACKGROUND: The purpose of this study was to determine the long-term local
      control, disease-free survival, and morbidity of fractionated high-dose-rate
      brachytherapy (F-HDR) in infants and children with soft tissue sarcomas. PATIENTS
      AND METHODS: Fifteen children (13 girls and 2 boys, ages 5-101 months) with soft
      tissue sarcomas were treated with chemotherapy, organ-preserving surgery, and F
      HDR (36 Gy in 12 fractions) to post-chemotherapy volumes. External beam
      radiotherapy was not part of the primary treatment, although four patients (27%)
      subsequently received salvage external beam radiotherapy after treatment failure.
      Chemotherapy was administered to all patients based on their tumor histology and
      stage. RESULTS: After a median follow-up of 10 years (range 32-154 months), 12
      patients (80%) were alive without evidence of disease. Ten-year overall survival
      and local control rates were both 80% (12/15 children). The overall survival was
      better (91%) for children with microscopic residual versus gross residual disease
      (75%). With longer follow-up, grade 3 to 4 brachytherapy-related late morbidities
      increased from 8% (1/12) to 20% (3/15) and included trismus/osteonecrosis,
      vaginal stenosis, and periurethral fibrosis. There were two late complications
      associated with puberty that occurred 8 to 10 years after the initial treatments.
      Acute toxicity occurred in five patients (38%) and consisted primarily of grade 1
      to 3 skin and mucosal reactions. CONCLUSIONS: As the sole radiation modality, F
      HDR achieved excellent local control and disease-free survival in properly
      selected children with soft tissue sarcomas while preserving normal bone and
      organ development. A significant percentage of patients experience adverse late
      sequelae as a result of this treatment.

PMID- 12794523
TI  - WT1 mRNA in cerebrospinal fluid associated with relapse in pediatric
      lymphoblastic leukemia.
AB  - BACKGROUND: The goal was to assess a possible relationship between the detection
      of mRNA from WT1 gene in cerebrospinal fluid (CSF) and neoplastic relapse in
      pediatric patients being treated for lymphoid precursor cell neoplasms. PATIENTS
      AND METHODS: Ninety-four patients less than 19 years old with lymphoid precursor
      cell leukemia in hematologic remission and without central nervous system (CNS)
      compromise were included. Cytology, cytochemistry, cell count, and qualitative RT
      PCR were performed using routine CSF samples obtained during intrathecal
      chemotherapy administration. The main outcome measure was clinical, radiologic,
      and cytologic evidence of CNS, hematologic or any other type of neoplastic
      relapse. RESULTS: At some time during follow-up, 28.7% of the patients had a
      positive WT1 CSF test. Relapses included 10 patients with isolated hematologic, 4
      with isolated CNS, 1 with combined CNS and hematologic, and 1 with mediastinal
      relapse; the maximal follow-up period was 312 days. A statistically significant
      association was found between the detection of WT1 in CSF and CNS relapse.
      Adjusted hazard rate ratios of 5.04 (95% confidence interval 1.33-19.12) and 7.48
      (2.34-23.93) were estimated for isolated hematologic relapse and for all types of
      relapses, respectively. CONCLUSIONS: Although it is likely that the short follow
      up period underestimated the incidence of relapse, this study was able to
      identify a strong association between WT1 mRNA detection and CNS or hematologic
      relapse. These findings represent a potentially novel and useful approach for
      subclinical disease detection.

PMID- 12794524
TI  - The epidermal growth factor receptor HER2 is not a major therapeutic target in
      Ewing sarcoma.
AB  - BACKGROUND: Although chimeric EWS gene and Ets gene fusions are pathognomonic of
      Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET), the molecular
      pathogenesis of these pediatric malignancies is poorly understood. Recently, the
      human epidermal growth factor (HER)-2 receptor, which plays an important role in
      the biology of certain epithelial cancers, has been implicated in ES tumor cell
      line growth and chemosensitivity. MATERIALS: To investigate whether HER2 might be
      a rational target for ES/PNET therapy, five ES cell lines and 13 archival primary
      ES/PNET samples were examined by immunohistochemistry (IHC) and fluorescence in
      situ hybridization (FISH) for evidence of HER2 overexpression. RESULTS: Although
      several ES cell lines demonstrated modest constitutive HER2 expression by
      immunoblot, none of the ES cell lines or primary tumor samples showed evidence of
      HER2 overexpression by IHC or HER2 gene amplification by FISH. Moreover,
      treatment of human ES cell lines with the HER2-targeted agent trastuzumab
      (Herceptin) had little effect on cell survival, proliferation, or growth in semi
      solid medium. CONCLUSIONS: These results suggest that HER2 is not a biologically
      or therapeutically important pathway in ES/PNET.

PMID- 12794525
TI  - A controlled longitudinal study of the social functioning of children who
      completed treatment of cancer.
AB  - BACKGROUND: A follow-up assessment of social functioning was performed for
      children with cancer after completion of treatment. It was hypothesized that
      children who completed cancer treatment (CCT) would have more social problems
      than their peers who were not chronically ill (COMP) and that greater treatment
      intensity would be predictive of increasing social difficulties over time.
      PATIENTS AND METHODS: Peer, teacher, and self-reports of social functioning were
      obtained from 69 CCTs and 77 COMPs. Social reputation and social acceptance were
      evaluated cross-sectionally and longitudinally. RESULTS: Relative to COMPs, CCTs
      described themselves as more prosocial, were perceived by teachers as less
      aggressive, and were seen by peers as more sick, more tired, and as missing more
      school. Longitudinal analyses indicated that self-reported prosocial scores were
      significantly more stable over time for CCTs relative to COMPs. Children who
      received more intense treatment were perceived by peers as more prosocial and
      less aggressive, but as having fewer best friends 2 years after treatment ended.
      CONCLUSIONS: CCTs had minimal impact on their social functioning as a result of
      their experience with cancer for those children who have returned to school.
      These results suggest that routine interventions with regard to social
      functioning after treatment ends may not be warranted for most CCTs when an
      integrated program of psychosocial services coordinated by mental health
      professionals has been provided during treatment. However, children who have
      undergone especially intense treatment may be at some risk for social problems.

PMID- 12794526
TI  - Comparison of PFA-100 and bleeding time testing in pediatric patients with
      suspected hemorrhagic problems.
AB  - BACKGROUND: The bleeding time test is difficult to perform, standardize, and
      interpret in children. In this study the authors evaluated the sensitivity,
      specificity, and efficiency of the bleeding time test and the PFA-100 in a series
      of children referred for possible bleeding problems. PATIENTS AND METHODS:
      Between February 2000 and August 2001 patients aged more than 6 months and less
      than 18 years of age who were referred to the authors' institution for a
      hemostatic evaluation were included in the study if residual blood was available
      for testing on the PFA-100 instrument. Fifty-two children had platelet count,
      prothrombin time, partial thromboplastin time, bleeding time, and PFA-100 testing
      performed as well as an evaluation by a hematologist. For PFA-100 testing, 52
      patients had Col/Epi measurements; adequate sample remained for Col/ADP testing
      on 32. Additional testing for diagnostic purposes was at the discretion of the
      treating physician. RESULTS: Use of the Col/Epi cartridge in the PFA-100
      instrument offered 100% sensitivity and 97% specificity for detection of
      qualitative platelet abnormalities, compared with 37% and 88%, respectively, for
      bleeding time testing. For pediatric patients with von Willebrand disease, the
      sensitivity was 100% using the Col/Epi cartridge, compared with 17% for the
      bleeding time test. The sensitivities for combined qualitative platelet defects
      and von Willebrand disease using the Col/Epi or Col/ADP cartridges were 100% and
      87%, respectively, compared with 37% for the bleeding time test. CONCLUSIONS: The
      PFA-100 is a more efficient test; it can replace the bleeding time test as a
      component of the laboratory evaluation of children with a potential bleeding
      problem.

PMID- 12794527
TI  - Serum levels of interleukin-1 receptor antagonist and tumor necrosis factor-alpha
      are elevated in children with Langerhans cell histiocytosis.
AB  - PURPOSE: Langerhans cell histiocytosis (LCH) is a rare disease with variable
      prognosis in which lesions and clinical features suggest that pro- and anti
      inflammatory cytokines may be involved in its pathogenesis. The authors wished to
      evaluate whether serum levels of interleukin-1 receptor agonist (IL-1Ra) and
      tumor necrosis factor-alpha (TNF-alpha) are elevated in children with LCH and
      decrease after chemotherapy. PATIENTS AND METHODS: Circulating levels of IL-1Ra
      and TNF-alpha were measured in 23 and 8 children with LCH, respectively, and 7
      pediatric controls using commercially available ELISA kits. All patients
      fulfilled the Histiocyte Society LCH Protocols criteria for diagnosis,
      stratification, and treatment. RESULTS: Pretreatment concentrations of IL-1Ra and
      TNF-alpha were found to be significantly elevated in patients with LCH compared
      with controls. Among LCH substages, a significant difference in IL-1Ra values was
      observed between individuals with single-system single-site disease vs.
      multisystem disease with risk-organ dysfunction. In all eight patients evaluated,
      IL-1Ra levels decreased after 6 weeks of chemotherapy. Lower values of TNF were
      observed in three patients after treatment. A positive and significant
      correlation between IL-1Ra and TNF serum concentrations was found. CONCLUSIONS:
      Patients with LCH have elevated levels of IL-1Ra and TNF, which decrease after
      chemotherapy.

PMID- 12794528
TI  - Cerebrovascular complications of L-asparaginase in the therapy of acute
      lymphoblastic leukemia.
AB  - L-asparaginase is frequently used in combination therapy for the treatment of
      lymphoid malignancies. We report 5 children aged between 8 and 14 years with
      neurologic complications presenting with headache and seizures during the first
      three weeks of L-asparaginase treatment. Three patients had venous thrombosis,
      one presented a parenchymal hemorrhage, and one showed a peculiar encephalopathy
      with extended cortical and subcortical lesions suggesting a neurotoxic reaction.
      Decreased fibrinogen and antithrombin III levels were found. Early MRI is
      critical even in cases with mild neurologic symptoms. Diagnosis should be
      followed by early cessation of l-asparaginase application.

PMID- 12794530
TI  - Concordant rhabdoid tumor of the kidney in a set of identical twins with
      discordant outcomes.
AB  - We report identical twin boys who each had stage IV rhabdoid tumor of the left
      kidney at the age of 5 months and 2 years, respectively. The 5-month-old boy,
      despite receiving chemotherapy, died of progressive disease at the age of 12
      months. Following resection of the tumor, his twin brother was treated with 6
      cycles of combination chemotherapy consisting of cisplatinum, doxorubicin,
      vincristine, cyclophosphamide, and actinomycin-D alternating with ifosfamide and
      etoposide. After complete regression of lung and brain metastases, he received
      high-dose thiotepa, etoposide, and cyclophosphamide, followed by autologous
      peripheral stem cell rescue. The patient is presently alive and free of disease 6
      years posttransplant. High-dose chemotherapy followed by autologous stem cell
      transplant may be an effective front-line therapeutic approach for patients with
      metastatic rhabdoid tumor of the kidney.

PMID- 12794529
TI  - Acute lymphoblastic leukemia presenting with lactic acidosis and renal tubular
      dysfunction.
AB  - Acute lymphoblastic leukemia (ALL) in children can rarely present with severe
      lactic acidosis in the absence of a high white blood cell count or other
      complications. Renal tubular dysfunction with hypercalciuria and hypocalcemia in
      the absence of pre-existing renal disease or concurrent medications has not been
      described at presentation in childhood ALL. The authors describe a 7-year-old boy
      with ALL presenting with severe lactic acidosis and renal tubular dysfunction,
      both of which were refractory to conventional management and resolved rapidly
      with appropriate chemotherapy.

PMID- 12794531
TI  - Memory strategy training in children with cerebral infarcts related to sickle
      cell disease.
AB  - Cerebral infarcts occur in approximately 30% of children with sickle cell disease
      (SCD), but little information exists regarding remediation of associated
      cognitive deficits. The authors examined the benefits of training children with
      infarcts to use memory strategies. Six children with SCD-related infarcts
      received academic tutoring; three of these children received additional training
      in memory strategies (silent rehearsal to facilitate short-term memory and
      semantic organization to facilitate long-term memory). The performance of
      children receiving strategy training appeared to improve more than that of
      children receiving only tutoring. Memory in children with SCD-related infarcts
      may be enhanced through strategy training.

PMID- 12794532
TI  - Novel applications of recombinant factor VIIa for the management of pediatric
      coagulopathic diseases.
AB  - Recombinant factor VIIa (rFVIIa) was envisioned for the treatment of bleeding in
      hemophilia patients with inhibitors. In response to tissue factor expressed upon
      vessel wall injury, rFVIIa amplifies the thrombin burst primarily on membrane
      surfaces, including activated platelets. Because it is functional at a key point
      in the clotting cascade, rFVIIa shows promise as a therapeutic option for various
      bleeding situations. The prothrombin time (PT) is often used as a surrogate to
      monitor rFVIIa therapy. Using laboratory and clinical measures of outcome, the
      use of rVIIa as a therapeutic option in treating several different pediatric
      coagulopathic conditions is described.

PMID- 12794533
TI  - Gastrointestinal involvement in disseminated Langerhans cell histiocytosis (LCH)
      with durable complete response to 2-chlorodeoxyadenosine and high-dose
      cytarabine.
AB  - Successful treatment of infants with gastrointestinal involvement in Langerhans
      cell histiocytosis (LCH) has been poor, with no specific chemotherapeutic regimen
      of clear benefit. An 8-month-old male, diagnosed with LCH by skin and
      gastrointestinal biopsies, was treated with several cycles of 2
      chlorodeoxyadenosine, vinblastine and prednisone with only partial response.
      Ultimately, two cycles of 2-chlorodeoxyadenosine concomitant with high-dose
      cytarabine led to a durable complete response. Twenty-seven months since the last
      course of chemotherapy, the patient continues to thrive free of disease.
      Treatment with 2-chlorodeoxyadenosine and cytarabine should be considered for
      further study in patients with poor-prognosis LCH.

PMID- 12794534
TI  - Imatinib mesylate noncompliance simulating chronic myeloid leukemia resistance.

PMID- 12794535
TI  - Chromosome 20q deletion and progression to monosomy 7 in a patient with Shwachman
      Diamond syndrome without MDS/AML.

PMID- 12794537
TI  - Train-the-Trainer Project meets organization's strategic initiative for retention
      and continuous learning.
AB  - Increasing staff education needs, limited staff development resources, and
      retention of valuable staff are issues facing healthcare providers today. This
      article describes the use of project management methodology to design and
      implement a Train-the-Trainer (TTT) program. This TTT program describes how to
      enlist leadership support for staff presentation of educational offerings. The
      TTT program was designed to retain employees through staff development and meet
      the educational needs of the healthcare system.

PMID- 12794536
TI  - From nursing home to hospital and back again: an educational program to improve
      care for hospitalized nursing home patients.
AB  - Hospital nurses have little knowledge of the geriatric syndromes and the
      processes of caregiving in nursing homes. This lack of knowledge is a barrier to
      continuity of care for patients admitted to hospitals from nursing homes. An
      educational program, including both classroom and clinical components, was
      designed to help bridge this gap. A plan for dissemination to other hospital
      staff was developed by the 15 nurses who participated.

PMID- 12794538
TI  - Critical analysis of research papers.
AB  - Use of new nursing knowledge has improved nursing practice and patient care
      outcomes. However, the busy bedside duties nurses face constitute barriers to
      reading and evaluating research. The nurse may want to use new knowledge about
      pain assessment, wound care, preoperative fasting, and depression screening to
      improve practice but may lack the skills and know how to evaluate the research
      critically. Barriers to analysis of the research include confusing technical
      terminology, statistics, and unclear research reports. The nurse needs to
      understand and examine the steps, cohesiveness, merits, and weaknesses of the
      research to assess his or her level of confidence in the findings. This article
      describes the criteria for analysis of the sections of a research report and
      illustrates ways that sound research has improved patient care.

PMID- 12794539
TI  - ENTER: a care guide for successfully educating patients.
AB  - The role of the nurse as teacher is assumed and preparation for the patient at
      discharge becomes the ultimate responsibility of the nurse. Furthermore, patient
      education continues to grow in importance. Because of increasing demands on time
      and full schedules, nurses are in need of a quick and practical solution to
      offering valuable patient education. The ENTER acronym is written with the
      practicing nurse in mind. It is a simple framework that provides a model for
      staff development educators to use to assist nurses to become better patient
      educators.

PMID- 12794541
TI  - Instant teaching tools.

PMID- 12794540
TI  - Is computer-based instruction an effective way to present fire safety training to
      long-term care staff?
AB  - This study offers evidence that computer-based instruction is a feasible and
      effective alternative training method for long-term care staff. Participants were
      289 nursing facility staff randomly divided into two treatment groups. One group
      completed instructor-led (IL) fire safety training and the other completed
      computer-based (CB) training adapted from the IL version. Both the CB and IL
      groups significantly increased their scores from pre- to posttest. Differences
      between the two groups were not significant.

PMID- 12794542
TI  - Genital shedding of herpes simplex virus-2 DNA and HIV-1 RNA and proviral DNA in
      HIV-1- and herpes simplex virus-2-coinfected African women.

PMID- 12794543
TI  - Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly
      active antiretroviral therapy is associated with ongoing increased CD4 T cell
      activation and turnover.
AB  - To evaluate the relationship between T cell turnover, immune activation, and CD4
      recovery in HIV infection, 32 antiretroviral-naive HIV-1-infected patients were
      studied before and after initiation of highly active antiretroviral therapy
      (HAART). Elevated CD4 and CD8 T cell turnover (measured by Ki67) in HIV infection
      decreased with HAART in blood and lymphoid tissue. Increased peripheral CD4 T
      cell turnover was strongly associated with immune activation even after viral
      suppression to less than 50 copies/mL (R = 0.8; p <.001). Increased CD4 T cell
      turnover correlated strongly with CD4 cell counts both before (R = -0.6; p <.001)
      and after (R = -0.4; p =.05) HAART. In patients with baseline CD4 cell counts of
      less than 350/microL, decreases in CD4 T cell turnover with HAART significantly
      correlated with increases in CD4 cell counts. In addition, persistently elevated
      levels of CD4 T cell turnover after HAART were associated with incomplete CD4 T
      cell recovery despite HIV RNA levels of less than 50 copies/mL. These data
      suggest that immune activation is central to CD4 cell depletion in HIV infection
      and immune reconstitution with HAART.

PMID- 12794546
TI  - Pretreatment of chronic active hepatitis C in patients coinfected with HIV and
      hepatitis C virus reduces the hepatotoxicity associated with subsequent
      antiretroviral therapy.
AB  - Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral
      related hepatotoxicity, but little is known about the frequency of severe liver
      toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated).
      The aim of this prospective study of 105 patients was to compare the incidence of
      progression to severe antiretroviral-related liver toxicity in 66 patients
      pretreated (36 with interferon-alpha [IFNalpha], 30 with IFNalpha plus
      ribavirin), and 39 patients not pretreated. The subjects could choose whether to
      receive anti-HCV therapy. Severe liver toxicity was defined as alanine
      aminotransferase (ALT) level > or =5-times the upper limit of normal in patients
      with normal baseline levels and > or =3.5-times in those with increased baseline
      levels. The authors also estimated the hepatotoxicity-related risk of
      discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects
      (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39
      untreated patients (24-month survival: 94% +/- 2.9% vs. 85% +/- 5.8%). After
      adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and
      HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of
      patients not pretreated), and previous anti-HCV therapy, the risk of
      discontinuing anti-HIV treatment was significantly higher in the anti-HCV
      untreated patients (RR = 10.4; 95% CI: 1.6-66; p =.0127) and in those with
      increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p =.0005). The
      authors' data suggest that previous treatment of chronic active HCV is an
      independent factor associated with a decrease of severe liver toxicity as the
      result of a subsequent antiretroviral regimen. The authors also confirm that the
      baseline level of ALT is an important prognostic factor for increased liver
      damage during antiretroviral therapy.

PMID- 12794544
TI  - Uncommon mutations at residue positions critical for enfuvirtide (T-20)
      resistance in enfuvirtide-naive patients infected with subtype B and non-B HIV-1
      strains.
AB  - Enfuvirtide (T-20) is the lead compound of the new class of antiretroviral drugs
      called fusion inhibitors. T-20 resistance-associated mutations located in the
      heptad repeat 1 (HR-1) domain of gp41 have been described in vitro and in
      clinical trials. In this study, the authors investigated the primary genotypic T
      20 resistance in subtype B and non-B HIV-1 strains from patients at the beginning
      of their follow-up in the Luxembourg HIV Cohort as well as the emergence of
      primary resistance to T-20 in patients who had long-term infection with subtype B
      HIV-1 strains. HR-1 fragments including the gp41 amino acid 36-45, T-20-sensitive
      region were screened for amino acid variation. No classic T-20 resistance
      associated mutations were identified in subtype B or non-B isolates. However,
      several uncommon mutations were found at residues 37, 39, and 42 for subtype B
      isolates and at residue 42 for a subtype non-B isolate. The results indicate that
      primary genotypic T-20 resistance seems to be rare in HIV-1, regardless of
      subtype or prior antiretroviral therapy (excluding fusion inhibitors). However,
      episodic variation within HR-1 can occur and needs further phenotypic evaluation
      in accurate fusion inhibitor resistance assays.

PMID- 12794545
TI  - The complexity of HLA class II (DRB1, DQB1, DM) associations with disseminated
      Mycobacterium avium complex infection among HIV-1-seropositive whites.
AB  - Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1)
      genes have been extended to include the accessory genes DMA and DMB as
      determinants of disseminated Mycobacterium avium complex (DMAC) infection among
      HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases
      were matched with 176 controls in a nested case-control study. PCR-based HLA
      genotyping techniques were used to resolve variants of DRB1 and DQB1 to their
      four-digit or five-digit alleles, and single-strand conformation polymorphism was
      used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele
      occurred less frequently among DMAC cases than among controls (OR = 0.46, p
      =.02). Combinations of DRB1 alleles with or without specific DMA and DMB variants
      showed significant differences in distributions between the cases and controls,
      but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701)
      showed stronger positive associations with DMAC in the absence than in the
      presence of DMA*0102. Apparent joint effects of DRB1 and DM allelic combinations
      on occurrence and timing of DMAC suggest that class II disease relationships may
      be better predicted by biologically plausible interactive combinations than by
      polymorphisms in individual genes.

PMID- 12794547
TI  - Predose infant nevirapine concentration with the two-dose intrapartum neonatal
      nevirapine regimen: association with timing of maternal intrapartum nevirapine
      dose.
AB  - OBJECTIVE: To evaluate cord blood and predose nevirapine concentrations in
      infants exposed to the two-dose intrapartum neonatal nevirapine regimen. METHODS:
      The authors obtained plasma samples for nevirapine assay from cord blood and just
      prior to the 48-hours to 72-hours after birth neonatal nevirapine dose from a
      subset of infants participating in PACTG 316, a randomized, placebo-controlled
      trial of the two-dose intrapartum neonatal nevirapine regimen added to standard
      antiretroviral therapy. RESULTS: Nevirapine concentrations were measured in 109
      cord blood samples and 149 predose samples. Cord blood nevirapine concentrations
      were below the target concentration of 100 ng/mL (10-times the in vitro IC(50) of
      nevirapine against wild-type HIV) in eight (7%) of 109 infants (95% confidence
      interval [CI], 3%-14%); the concentrations in six of these infants were below the
      assay limit of quantitation. Predose infant nevirapine concentrations were below
      100 ng/mL in 23 (15%) of 149 infants (95% CI, 10%-22%); the concentrations in 13
      of these infants were below the assay limit of quantitation. Lower predose
      nevirapine concentrations were associated with lower cord blood concentrations
      and a shorter interval between maternal dosing and delivery. All but one of the
      infants with predose nevirapine concentrations below the assay limit of
      quantitation were born less than 2 hours after maternal dosing. CONCLUSION:
      Infants born less than 2 hours after maternal nevirapine dosing during labor
      should receive a dose of nevirapine immediately after birth in addition to the
      standard infant dose at 48 to 72 hours.

PMID- 12794549
TI  - Unprotected anal intercourse between potentially HIV-serodiscordant men who have
      sex with men, San Francisco.
AB  - BACKGROUND: Increasing trends in high-risk sexual behavior are noted among men
      who have sex with men (MSM) worldwide. Less information is available on
      unprotected sex between persons of different HIV serostatus. METHODS: From 1999
      through 2001, volunteers of a community-based organization conducted interviews
      of 10,579 MSM at gay-oriented venues in San Francisco and in neighborhoods with
      high-volume MSM pedestrian traffic. The questionnaire recorded demographic and
      risk behavior information, including self-reported and partners' HIV serostatus.
      RESULTS: Potentially serodiscordant unprotected anal intercourse (UAI) with at
      least 2 anal sex partners was reported by 12.7% and increased from 11.0% in 1999
      to 16.2% in 2001. Stratifying by self-reported HIV serostatus, 20.8% of HIV
      positive respondents, 12.1% of HIV-negative respondents, and 13.4% of MSM who did
      not know or report their own HIV serostatus had potentially serodiscordant UAI.
      Older MSM of white race were more likely to report potentially serodiscordant UAI
      among HIV-positive respondents, whereas younger MSM of white race were more
      likely to report potentially serodiscordant UAI among HIV-negative respondents.
      Among those with unknown HIV serostatus, MSM of color were more likely to engage
      in potentially serodiscordant UAI. CONCLUSION: Recent increases in UAI among MSM
      in San Francisco are not only the result of increases in UAI between persons of
      the same HIV serostatus. Prevention messages must address disclosure of HIV
      serostatus to sexual partners specifically tailored to groups according to age,
      community, and HIV serostatus.

PMID- 12794548
TI  - Complementary and alternative medicine use and substitution for conventional
      therapy by HIV-infected patients.
AB  - BACKGROUND: HIV-infected patients commonly use complementary and alternative
      medicine (CAM), but it is not known how often CAM is used as a complement or as a
      substitute for conventional HIV therapy. OBJECTIVES: To evaluate the prevalence
      and factors associated with CAM use with potential for adverse effects and CAM
      substitution for conventional HIV medication. DESIGN AND PARTICIPANTS: Cross
      sectional survey of U.S. national probability sample of HIV-infected patients
      (2,466 adults) in care from December 1996 to July 1997. MAIN OUTCOME VARIABLES:
      Any CAM use, CAM use with potential for adverse effects, and use of CAM as a
      substitute for conventional HIV therapy. Substitution was defined as replacement
      of some or all conventional HIV medications with CAM. RESULTS: Fifty-three
      percent of patients had recently used at least one type of CAM. One quarter of
      patients used CAM with the potential for adverse effects, and one-third had not
      discussed such use with their health care provider. Patients with a greater
      desire for medical information and involvement in medical decision making and
      with a negative attitude toward antiretrovirals were more likely to use CAM.
      Three percent of patients substituted CAM for conventional HIV therapy. They were
      more likely to desire involvement in medical decision-making (odds ratio, 1.8;
      95% confidence interval, 1.0-3.2) and to have a negative attitude toward
      antiretrovirals (odds ratio, 7.8; 95% confidence interval, 3.0-19.0).
      CONCLUSIONS: Physicians should openly ask HIV-infected patients about CAM use to
      prevent adverse effects and to identify CAM substitution for conventional HIV
      therapy.

PMID- 12794550
TI  - Economic implications of failure to reduce incident HIV infections by 50% by 2005
      in the United States.
AB  - BACKGROUND: The Centers for Disease Control and Prevention have set a national
      goal of reducing new HIV infections by 50% by 2005 in the United States. There
      are no available published estimates of the economic consequences of failure to
      meet this national goal, however. OBJECTIVES: The purpose of this article is to
      calculate the potential net economic implications of a failure to meet the
      national HIV prevention goal of reducing new HIV infections by 50% by 2005.
      METHODS: Standard methods of cost-effectiveness analysis were used to determine
      1) the excess number of HIV infections incurred if the goal is not met and 2) the
      excess net medical costs (without the cost of an expanded HIV prevention program
      in the United States) incurred if the goal is not achieved. RESULTS: Base case
      results indicate that if the goal is not met, 130,000 excess HIV infections will
      occur between the present and 2010 and that the excess net medical costs incurred
      will total over $18 billion during the same time frame. Sensitivity analyses
      indicate that although changes in some parameter values do alter the quantitative
      results, none alter the basic qualitative finding that even dramatically expanded
      HIV prevention efforts that reduce new HIV infections by 50% are actually cost
      saving to society. CONCLUSIONS: The human and fiscal stakes of meeting the CDC's
      national HIV prevention goal of reducing new infections by 50% by 2005 are
      sufficiently large to make the achievement of this goal an urgent public health
      priority.

PMID- 12794551
TI  - Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected
      mothers.
AB  - Although children born to HIV-infected (HIV+) women receiving antiretroviral
      therapy during pregnancy show virtually no adverse clinical effects at birth, the
      antiretroviral nucleoside analog drugs are known to damage nuclear and
      mitochondrial DNA. In this study, biomarkers of mitochondrial toxicity and
      genotoxicity have been examined in a well-characterized sample set consisting of
      infants born to HIV-uninfected (HIV-) mothers (n = 30), and HIV- infants (n = 20)
      born to HIV-infected (HIV+) mothers who received either no antiretroviral therapy
      (n = 10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) during pregnancy (n =
      10). DNA from cord blood leukocytes and peripheral blood leukocytes taken at 1
      and 2 years of age was examined for loss of mitochondrial DNA (mtDNA) and
      telomere integrity. Telomere length, a measure of nuclear DNA damage, was the
      same in all infants at birth and at age 1 year. The quantity of mtDNA was
      assessed relative to nuclear DNA using a polymerase chain reaction-based
      chemiluminescence detection (PCR-CID) method that determined mitochondrial D Loop
      gene copies relative to nuclear 18S RNA gene copies by comparison with a standard
      curve. MtDNA quantity was expressed as a ratio of gene copy numbers. In infants
      of uninfected mothers (AZT-/HIV-) at the three time points, the ratios were 442
      to 515, whereas in infants of untreated AZT-/HIV+ mothers the ratios were 261 to
      297, and in infants of AZT-treated (AZT+/HIV+) mothers the ratios were 146 to
      203. At all three time points, differences between the AZT-/HIV- group and the
      two HIV+ groups were statistically significant (p <.05), and differences between
      the AZT-/HIV+ and AZT+/HIV+ groups were also statistically significant (p <.05),
      demonstrating that AZT exposure causes a persistent depletion of mtDNA. The study
      shows that children of HIV+ mothers are at risk for mitochondrial damage that is
      further increased in infants of mothers receiving AZT during pregnancy.

PMID- 12794552
TI  - Impact of tuberculosis on HIV disease progression in persons with well-documented
      time of HIV seroconversion.
AB  - Tuberculosis (TB) enhances HIV replication in vitro, but its impact on HIV
      progression at the population level is not established. Studies from
      industrialized and nonindustrialized countries show contradictory results as to
      whether TB accelerates HIV progression, although no studies have been conducted
      in persons with well-documented seroconversion times. Data from HIV
      seroconverters from 19 cohorts were analyzed to examine the effect of TB on HIV
      progression comparing persons with TB and persons without TB infected by HIV for
      the same length of time. TB and other AIDS-defining conditions (ADCs) were fitted
      as time-dependent covariates, adjusting for age, sex, transmission category,
      calendar year at risk, and cohort, using Cox proportional hazards models and
      allowing for late entry. Of 4398 seroconverters, 1294 (29%) developed AIDS. TB
      accounted for 72 (5.6%) of initial ADCs and for 105 (5.7%) of all ADCs. Survival
      from HIV seroconversion shows that compared with AIDS-free subjects, the risk of
      death associated with TB as an initial ADC (hazard ratio [HR] = 23.23, 95% CI:
      14.60-36.96) does not differ from that associated with Kaposi sarcoma (HR =
      23.47, 95% CI: 16.66-33.05) or esophageal candidiasis (OC)/Pneumocystis carinii
      pneumonia (PCP) (HR = 30.97, 95% CI: 24.38-39.34) but is lower than that for
      opportunistic infections other than TB, OC/PCP (HR = 46.83, 95% CI: 37.86-47.94)
      and high-grade non-Hodgkin lymphomas/invasive cervical carcinoma (HR = 92.71, 95%
      CI: 60.83-141.3). The lowest risk of death was seen, as expected, in AIDS-free
      subjects. HIV progression is not inherently faster in subjects who develop TB
      compared with other individuals with AIDS who have been infected by HIV for the
      same length of time in countries where TB treatment is widely available.

PMID- 12794554
TI  - Rapid whole-blood finger-stick test for HIV antibody: performance and
      acceptability among women in northern Thailand.
AB  - Although use of rapid HIV antibody tests of finger-stick blood specimens could
      expand voluntary counseling and testing in areas where fear of venipuncture and
      delays in learning test results are barriers, there is little information on
      performance and acceptability of these tests in Asia. We used the Hema. Strip HIV
      1/2 test (Saliva Diagnostic Systems, Vancouver, WA) in a prospective cohort study
      of HIV seroincidence among women in northern Thailand from 1998 to 1999. Nurses
      obtained whole-blood specimens by finger-stick testing and provided test results
      and counseling at each visit. Acceptability of the rapid test was assessed at the
      first 6-month follow-up visit. HIV-1 seroprevalence among the 804 women screened
      at enrollment was 3.1%. Positive rapid test results from 25 women were confirmed
      by enzyme immunoassay and Western blot analysis using serum obtained by
      venipuncture. Of the 741 women who returned for follow-up, 56% preferred specimen
      collection by finger-stick testing to venipuncture, 80% preferred immediate
      rather than delayed test results, 79% preferred the rapid test method to typical
      testing methods, and 97% were satisfied with the test method used. Results from
      this study demonstrate the utility and acceptability of the rapid finger-stick
      test for HIV antibody among women in northern Thailand.

PMID- 12794553
TI  - Viagra use in a community-recruited sample of men who have sex with men, San
      Francisco.
AB  - The authors conducted a community-based anonymous survey of 837 men who have sex
      with men (MSM) to gauge the extent of Viagra (sildenafil citrate) use, its
      association with high-risk sexual behavior, and its combination with other drugs.
      Participants' mean age was 35 years, 67% were white, and 66% had a college
      degree. The majority (76%) reported anal sex in the past 6 months, with 49%
      reporting always using condoms. Overall, 32% had ever used Viagra (CI: 29%-36%).
      Significant independent predictors of Viagra use were white race, older age, HIV
      positivity, illicit drug use, and having had unprotected anal sex with
      potentially serodiscordant partners. Over one third of Viagra users had combined
      Viagra with other drugs, 18% with amyl nitrate. Only a minority (44%) obtained
      Viagra under the care of a physician. For some MSM, Viagra appears to be an
      emerging contributing factor to unsafe sex, potentially increasing HIV
      transmission. HIV care and prevention providers should target Viagra users for
      enhanced education on safer sex and potentially harmful drug interactions.

PMID- 12794555
TI  - Needle exchange and injection drug use frequency: a randomized clinical trial.
AB  - Despite a lack of evidence that needle exchange programs (NEPs) cause an increase
      in injection drug use, there are still concerns over fostering increased
      injection behavior with NEPs. The design was a randomized controlled trial
      conducted from May 1997 to June 2000 comparing injection drug users (IDUs) who
      are randomly assigned to have access to an NEP versus training in how to purchase
      needles and syringes (NS) at pharmacies. Of 653 IDUs recruited into the study,
      600 were randomized: 426 were followed-up at 6 months, and 369 were followed-up
      at 12 months. Four hundred ninety were followed up at least once. There was no
      difference in the number of injections over time between the NEP and the Pharmacy
      Sales arms of the study or in the percentage of positive urine test results over
      time between the NEP and the Pharmacy Sales arms of the study for morphine and
      amphetamine. The decrease in the presence of cocaine was marginally greater
      between the arms of the study. The results do not support the hypothesis of NEPs
      causing an increase in injection drug use. This clinical trial provides the
      strongest evidence to date that needle exchanges do not produce this negative
      effect.

PMID- 12794556
TI  - Kaposi's sarcoma in Uganda: risk factors for human herpesvirus 8 infection among
      blood donors.
AB  - Human herpesvirus 8 (HHV-8) is etiologically linked to Kaposi's sarcoma, a common
      cancer in Uganda. The authors assessed HHV-8 seroprevalence, risk factors for
      infection, and HHV-8 assays in a cross-sectional study of Ugandan blood donors.
      Of 3,736 specimens, the authors selected 203 reactive for HIV, hepatitis B
      surface antigen (HBsAg), or syphilis, and, randomly, 203 nonreactive specimens.
      For HHV-8 testing, the authors used two peptide-based enzyme-linked immunosorbent
      assays (EIAs), ORFK8.1 and ORF65, and an immunofluorescence assay (IFA).
      Specimens reactive in at least two assays or on IFA alone were considered HHV-8
      seropositive. Prevalence estimates were weighted to account for the sampling
      scheme. Overall HHV-8 seroprevalence was 40%. HHV-8 seroprevalence was higher
      among HBsAg-positive donors (53%) than HBsAg-negative donors (39%; p =.02) and
      higher among HIV-positive donors (63%) than HIV-negative donors (39%; p <.001).
      HHV-8 seroreactivity showed no trend with age. Kappa values for assay
      concordances were 0.68 (ORFK8.1 EIA and IFA), 0.37 (ORF65 EIA and K8.1 EIA), and
      0.29 (ORF65 EIA and IFA). The association between HHV-8 and HBsAg positivity and
      the lack of association between HHV-8 and age point to primarily nonsexual HHV-8
      transmission during childhood. The association with HIV indicates sexual
      transmission may also occur. The role of ORF65 EIA in testing specimens from
      Africa warrants further evaluation.

PMID- 12794557
TI  - Assessment of adherence to antiviral therapy in HIV-infected children using the
      Medication Event Monitoring System, pharmacy refill, provider assessment,
      caregiver self-report, and appointment keeping.
AB  - The authors sought to assess the utility of the electronic Medication Event
      Monitoring System (MEMS) in monitoring adherence to highly active antiretroviral
      therapy (HAART) in HIV-infected children and to compare this with other methods
      of adherence assessment. Twenty-six perinatally HIV-infected children being
      treated with three or more antiretroviral medications and their caregivers were
      enrolled and prospectively followed-up for 6 months. Adherence was assessed using
      MEMS monitoring of one antiretroviral, pharmacy refill records of all
      antiretrovirals, a caregiver self-report interview, a physician/nurse
      questionnaire, and appointment-keeping behavior. Viral loads measured at the end
      of the 6-month period were compared with the various adherence assessment
      methods. Adherence rates for the MEMS-monitored medication ranged from 12.7% to
      97.9% (median = 81.4%), and 11 of the participants (42%) had less than 80%
      adherence using this method. A MEMS adherence rate greater than 80% was
      associated with viral load below the threshold of detection 6 months after
      enrollment (p <.001). Although not as robust, pharmacy refill rates for all
      antiretroviral medications were also associated with virologic response. The
      highest specificity was attained when both MEMS and pharmacy refill were used in
      combination. Physician assessment of adherence rate as well as appointment
      keeping behavior was associated with virologic response, whereas caregiver self
      report was not.

PMID- 12794558
TI  - HIV-2 subtype circulating in India (south).
AB  - The genetic types and subtypes of HIV vary from region to region. This study
      looked at the relative prevalence of HIV-2 subtypes in south India. Nucleotide
      sequencing of the HIV-2 envelope V3 region of strains from 11 individuals
      infected with HIV-2 and one individual who had dual infection with HIV-1 and HIV
      2 was performed. Phylogenetic analysis showed that all individuals were infected
      with HIV-2 subtype A. These strains were from individuals who live in different
      regions of south India. In all, up to present, 17 strains inclusive of the
      authors' 12 have been sequenced, and subtype A of HIV-2 is seen in both
      monoinfections and dual infections with HIV-1 in India.

PMID- 12794559
TI  - HIV infection and associated risks among young men who have sex with men in a
      Florida resort community.
AB  - OBJECTIVE: Several recent studies have reported high rates of sexual risk-taking
      and HIV infection among young men who have sex with men (MSM). Most of these
      studies used samples of convenience. The authors obtained population-based data
      on young MSM living in South Beach (Miami Beach, Florida), a resort community
      where some of the highest AIDS rates in the United States have been reported.
      METHODS: A household probability sample was drawn to survey unmarried 18- to 29
      year-old MSM living in South Beach. Subjects were interviewed, completed self
      administered questionnaires, and provided oral specimens for HIV antibody
      testing. RESULTS: From the 2,622 screened residential units, 100 mostly white and
      Hispanic MSM (92.6% of eligible participants) were enrolled in the study. Fifteen
      percent of the sample tested positive for antibodies to HIV. White and Hispanic
      MSM had similar rates. Forty-five percent of the sample reported engaging in
      unprotected anal intercourse (UAI) in the prior 12 months, and 31% reported UAI
      with a nonprimary partner. The estimated annual incidence of HIV infection was
      6.3%. CONCLUSION: The high prevalences of UAI and HIV infection in South Beach
      attest to a previously undocumented public health concern. The extremely high
      estimated incidence for young MSM in South Beach highlights the urgent need for
      more effective risk-reduction interventions and further epidemiological research
      on resort areas.

PMID- 12794560
TI  - Increasing trend of Cesarean deliveries in HIV-infected women in the United
      States from 1994 to 2000.
AB  - BACKGROUND: Meta-analysis and randomized clinical trial results reported in June
      1998 indicated a significant reduction in perinatal HIV transmission rates among
      mothers undergoing a cesarean section (C-section). OBJECTIVE: The objective of
      this study was to examine recent trends in and factors associated with C-section
      deliveries among HIV-infected women in the United States. DESIGN: A multisite
      pediatric medical record review of a cohort of HIV-exposed and HIV-infected
      infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467)
      and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was
      conducted. SETTING/PATIENTS: All infants born between 1994 and 2000 to HIV
      positive mothers referred to the PSD study or to a Pediatric HARS hospital or
      clinic site were enrolled. RESULTS: The proportion of deliveries by C-section was
      steady at about 20% from 1994 through June 1998. From July 1998 through December
      2000, this proportion increased to 44% in the PSD study and to nearly 50% in the
      Pediatric HARS. On analysis by multiple logistic regression, delivery of infants
      by C-section was associated with the release of study results (OR = 2.83),
      delivery in four PSD sites in reference to Texas (OR: 2.02-1.43), having private
      medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR =
      1.43). CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase
      in C-section rates mainly among HIV-infected women in the United States after the
      release of the meta-analysis and randomized clinical trial results in 1998. This
      finding highlights the rapid impact of study results on obstetric practice. It
      underscores the critical role of prenatal care in offering perinatal
      interventions such as scheduled C-section when indicated to reduce the likelihood
      of HIV transmission.

PMID- 12794562
TI  - New sexually transmitted diseases in HIV-infected patients: markers for ongoing
      HIV transmission behavior.
AB  - OBJECTIVE: The objective of this study was to describe the rate of new sexually
      transmitted diseases (STDs) among HIV-infected patients and to define the
      behavioral and clinical characteristics of HIV-infected patients who return with
      a new STD in follow-up. DESIGN: The study design was a record-based clinical
      cohort study focusing on patients testing HIV-seropositive in the STD clinics of
      Baltimore, Maryland from 1993 to 1998. METHODS: The authors identified those HIV
      infected patients later diagnosed with an STD in follow-up and compared their
      demographic, behavioral, and clinical characteristics with those who were not
      diagnosed with an STD in follow-up. RESULTS: Of 796 men and 354 women with HIV
      infection, 13.9% of men and 11.9% of women were diagnosed with an STD after their
      initial HIV diagnosis. HIV-infected men returned with a new STD at a rate of 7
      cases per 100 person-years; HIV-infected women returned at a rate of 5.6 cases
      per 100 person-years. In men, multiple sex partners and sex worker contact were
      associated with a subsequent STD diagnosis (OR = 1.67, p =.037; OR = 1.82, p
      =.015, respectively). In women, age younger than 30 years was associated with the
      diagnosis of an STD after the diagnosis of HIV infection (OR = 2.94, p =.0009).
      CONCLUSIONS: Patients diagnosed with HIV in an STD clinic setting commonly return
      with new STDs in follow-up, suggesting continued exposure of HIV to others. More
      intensive screening and counseling interventions focused on STD prevention in
      those with HIV infection is a necessary HIV prevention strategy.

PMID- 12794561
TI  - High genetic diversity of HIV-1 strains in Chad, West Central Africa.
AB  - The genetic diversity of HIV-1 strains in Chad was documented with a total of 107
      samples from patients attending the general hospital in N'Djamena, the capital
      city of Chad. The genetic subtypes were identified in the V3-V5 env and p24 gag
      regions by sequence and phylogenetic tree analyses. Of the 107 strains, 78 had
      the same subtype/CRF designation between env and gag. Four subtypes and three
      CRFs were found to cocirculate: subtype A, 20.5%; subtype D, 18.7%; CRF02_AG,
      13.1%; CRF11_cpx, 13.1%; subtype G, 3.7%; CRF01_AE, 2.8%; and subtype F1, 0.9%.
      The remaining 29 strains (27%) had discordant subtypes or CRF designations
      between env and gag; in 15 of these 29 strains, a CRF was involved in the
      recombination event, and 10 were subtype G in gag and subtype A in env, forming a
      separate subcluster within subtypes G and A. Subtype D strains represent almost
      20% of the HIV-1 strains circulating in Chad and form a separate subcluster in
      gag and env. Nearly full-length genome sequencing for two such strains (99TCD
      MN011 and 99TCD-MN012) revealed that they represent nonrecombinant subtype D
      variants. Compared with neighboring countries, the genetic subtype distribution
      of HIV-1 strains in Chad is unique for several reasons: lower prevalence of
      CRF02, high prevalence of CRF11 and subtype D, and absence of CRF06. These data
      clearly show that subtype distribution is very heterogeneous in Africa, probably
      the result of different founder effects.

PMID- 12794563
TI  - Assessment of adherence to triple antiretroviral treatment including indinavir:
      role of the determination of plasma levels of indinavir.
AB  - OBJECTIVE: To assess the contribution of the determination of concentrations of
      indinavir (IND) in plasma to the assessment of self-reported adherence and
      keeping of appointments to withdraw drugs from the hospital pharmacy. PATIENTS
      AND METHODS: Adherence was assessed using three criteria: questionnaires,
      punctuality at appointments to withdraw drugs, and plasma concentrations of IND.
      Blood samples were obtained from 106 HIV-infected patients who had been receiving
      IND in combination with two nucleoside reverse transcriptase inhibitors for
      longer than 6 months. Logistic regression analysis was carried out, and receiver
      operating characteristic curves were drawn. RESULTS: The kappa index showed a low
      concordance for the three measures. When pharmacy appointments and self-report
      are used together, the nondetection of drug levels is more reliably predicted
      (AUC = 0.75). With the viral load as the gold standard, plasma levels contribute
      nothing to the information given by the other two measures combined (AUC = 0.63,
      AUC = 0.64). CONCLUSION: Measurement of adherence to highly active antiretroviral
      therapy is complex. Because there is no gold standard for it, we demonstrated
      that each of three common adherence measures has shortcomings that can be
      minimized in a combined measurement system. Indinavir plasma levels appear to
      provide no additional information, so further studies are undoubtedly necessary.

PMID- 12794565
TI  - AIDS wasting syndrome: trends, influence on opportunistic infections, and
      survival.
AB  - The authors examined data from a large cohort of HIV-infected persons to
      demonstrate recent trends in wasting syndrome, to examine the influence of
      wasting syndrome on the incidence of other opportunistic illnesses, and to
      explore if any of the commonly prescribed treatments for wasting are associated
      with improved survival. Kaplan-Meier analysis and multivariate left-truncated Cox
      models were used to estimate time to death after the first diagnosis of wasting
      syndrome and to quantify the association between the covariate and mortality,
      respectively. The incidence of wasting declined during 1992 through 1999, with
      the most marked rate of decline occurring after 1995. The incidence of AIDS- and
      non-AIDS-defining illnesses was generally high at or after a diagnosis of wasting
      syndrome. Factors significantly associated with improved survival include having
      a CD4+ count of > or =200 cells/L during the interval of the wasting syndrome
      diagnosis and antiretroviral therapy with two or more drugs at or after the
      diagnosis of wasting syndrome. Prescription of oxandrolone was associated with
      improved survival, but the results did not quite reach statistical significance.
      The authors' study provides supportive information that treatment of wasting
      syndrome may have a favorable impact on survival.

PMID- 12794564
TI  - HIV prevalence and risks among injection and noninjection drug users in northern
      Thailand: need for comprehensive HIV prevention programs.
AB  - The authors sought to determine sociodemographic and sexual and drug use risk
      factors for HIV infection among drug users in northern Thailand adjacent to the
      Golden Triangle. The authors enrolled patients admitted for inpatient drug
      detoxification at one treatment center in northern Thailand and studied HIV risks
      and prevalence using an interviewer-administered questionnaire and serum
      collection with HIV pretest and posttest counseling. Between February 1, 1999 and
      January 31, 2000, 1865 patients admitted for opiate and methamphetamine
      dependence completed study procedures. Overall HIV prevalence was 10.3%: 30.0%
      among 513 injection drug users (IDUs) and 2.8% among non-IDUs (OR = 14.8, 95% CI:
      10.2, 21.6). HIV seroprevalence was 2.4% among exclusive methamphetamine users
      (98% of whom are non-IDUs) and 3.4% among opium smokers. Injection drug use was
      the dominant risk factor in multivariate models. Although Thailand is widely
      recognized as having a successful national response to the heterosexual HIV
      epidemic, seroprevalence in IDUs remains high. Despite a sharp increase of non
      IDUs admitted to the drug treatment center, HIV infection and risks remained high
      among IDUs in northern Thailand. HIV prevention campaigns need to focus on IDUs
      and to implement harm reduction strategies to reduce transmission to IDUs and
      further contain the HIV epidemic in Thailand.

PMID- 12794566
TI  - Assessing usual care in clinical trials of adherence interventions for highly
      active antiretroviral therapy.

PMID- 12794567
TI  - Delayed-type hypersensitivity skin testing can predict CD4 count increase in HIV
      patients with poor immunologic response to HAART.

PMID- 12794568
TI  - CD4 cell count among HIV-infected patients with an AIDS-defining disease: higher
      count in patients coinfected than in those not coinfected with human T-cell
      lymphotropic virus type I.

PMID- 12794569
TI  - Randomized, controlled trial of biofeedback with anal manometry, transanal
      ultrasound, or pelvic floor retraining with digital guidance alone in the
      treatment of mild to moderate fecal incontinence.
AB  - BACKGROUND: A prospective, three-armed, randomized, controlled trial was
      performed to assess whether pelvic floor exercises with biofeedback using anal
      manometry or transanal ultrasound are superior to pelvic floor exercises with
      feedback from digital examination alone in terms of continence, quality of life,
      physiologic sphincter strength, and compliance. Its secondary objectives were to
      assess whether there are any differences in these outcomes between biofeedback
      with transanal ultrasound vs. anal manometry and to correlate the physiologic
      measures with clinical outcome. METHODS: One hundred twenty patients with mild to
      moderate fecal incontinence were randomized into one of three treatment groups:
      biofeedback with anal manometry, biofeedback with transanal ultrasound, or pelvic
      floor exercises with feedback from digital examination alone. Commencing one week
      after an initial 45-minute assessment session, patients attended monthly
      treatments for a total of five sessions. Each session lasted 30 minutes and
      involved sphincter exercises with biofeedback that involved instrumentation or
      digital examination alone, and patients were encouraged to perform identical
      exercises twice per day between outpatient visits. RESULTS: One hundred two
      patients (85 percent) completed the four-month treatment program. Across all
      treatment allocations, patients experienced modest but highly significant
      improvements in all nine outcome measures during treatment, with 70 percent of
      all patients perceiving improvement in symptom severity and 69 percent of
      patients reporting improved quality of life. With the possible exception of
      isotonic fatigue time, there were no significant differences between the three
      treatment groups in compliance, physiologic sphincter strength, and clinical or
      quality-of-life measures. Correlations between physiologic measures and clinical
      outcomes were much stronger with ultrasound-based measures than with manometry.
      CONCLUSIONS: Although patients in this study who completed pelvic floor exercises
      with feedback from digital examination achieved no additional benefit from
      biofeedback and measurement with transanal ultrasound or manometry, it may be
      that the guidance received through digital examination alone offered patients in
      the pelvic floor exercise group an effective biofeedback mechanism. Contrary to
      our hypothesis, the use of transanal ultrasound offered no benefit over
      manometry, but the use of ultrasound for isotonic fatigue time and isometric
      fatigue contractions provided potentially important physiologic measures that
      require further study. This study has confirmed, through a large sample of
      patients, that pelvic floor retraining programs are an effective treatment for
      improving physiologic, clinical, and quality-of-life parameters in the short
      term.

PMID- 12794570
TI  - Extended two-year results of radio-frequency energy delivery for the treatment of
      fecal incontinence (the Secca procedure).
AB  - PURPOSE: This study evaluated the durability and long-term safety of radio
      frequency energy delivery for fecal incontinence (Secca procedure). METHODS: This
      was an extended follow-up of a prospective study in which patients with fecal
      incontinence of various causes underwent radio-frequency energy delivery to the
      anal canal muscle. The Cleveland Clinic Florida Fecal Incontinence Scale (0-20),
      fecal incontinence-related quality-of-life score, and Medical Outcomes Study
      Short Form 36 were administered at baseline and at 1, 2, 3, 6, 12, and 24 months
      after the procedure. Differences between baseline and follow-up were analyzed
      with the Wilcoxon signed-rank test. RESULTS: Ten females (aged 55.9 +/- 9.2
      (range, 44-74) years) were treated. At two-year follow-up, the mean Cleveland
      Clinic Florida Fecal Incontinence Scale score was improved from 13.8 to 7.3 (P =
      0.002), with eight patients having scores of < or =10. All fecal incontinence
      related quality-of-life score parameters were improved, including lifestyle (from
      2.3 to 3.3; P = 0.002), coping (from 1.7 to 2.7; P = 0.002), depression (from 2.4
      to 3.4; P = 0.004), and embarrassment (from 1.5 to 2.4; P = 0.008). There was no
      decrement in effect noted in any parameter between 12 and 24 months (P > 0.2).
      The social function component of the Short Form 36 improved from 50 to 82.5 (P =
      0.04), whereas there was an improvement trend for the mental component summary of
      the Short Form 36 from 38.3 to 48.1 (P = 0.11). Protective pad use was eliminated
      in four of the seven baseline users. There were no long-term complications, such
      as stricture, pain, or constipation. CONCLUSIONS: A significant improvement in
      symptoms of fecal incontinence and quality of life persists two years after radio
      frequency delivery to the anal canal, which demonstrates durability of this
      intervention.

PMID- 12794571
TI  - Long-term follow-up of dynamic graciloplasty for fecal incontinence.
AB  - PURPOSE: Graciloplasty has been used as a treatment for end-stage fecal
      incontinence since 1946. Electric stimulation with an implantable pulse generator
      has existed for 15 years. The gracilis muscle is wrapped around the anal canal
      and stimulated by intramuscular electrodes connected with an implantable pulse
      generator. Initial reports have been promising, but long-term results have not
      been presented to date. METHODS: Data of 200 consecutive patients with a follow
      up of at least two years were analyzed in a prospective manner from 1986 until
      1999. RESULTS: The overall success rate was 72 percent. In patients with fecal
      incontinence caused by trauma, the rate was 82 percent. Once continent, patients
      remained continent after a median follow-up of 261 (standard deviation, 132)
      weeks. Median survival of the implantable pulse generator until battery
      expiration was 405 weeks. Disturbed evacuation remained a problem in 16 percent
      of all patients. Complications were frequent but treatable. CONCLUSION: Dynamic
      graciloplasty is a good, cost-effective treatment for fecal incontinence with
      results lasting for a median of more than five years.

PMID- 12794572
TI  - Artificial bowel sphincter: long-term experience at a single institution.
AB  - PURPOSE: This study was undertaken to evaluate a single-institution experience
      with the Acticon artificial bowel sphincter for the treatment of intractable
      fecal incontinence. METHODS: At the University of Minnesota, 45 consecutive
      patients underwent artificial bowel sphincter placement (Group I, 1989-1992, n =
      10; Group II, 1997-2001, n = 35). Group I was reviewed retrospectively and Group
      II prospectively. RESULTS: The outcome for Group I patients was initially
      reported in 1995 (mean age, 32; range, 15-52 years; 7 males). Of these 10
      patients, 4 required explantation (2 required stomas), and 6 have a functional
      artificial bowel sphincter; 2 patients had devices successfully replaced for
      fluid leaks (at 6 and 10 years). In Group II, artificial bowel sphincter
      placement was attempted in 37 patients and was successful in 35 (mean age, 47;
      range, 18-72 years; 11 males). A total of 14 patients required explantation, 12
      (34 percent) for infection and 2 (6 percent) for pain. In total, 13 patients have
      required 21 revisions, including 7 complete device replacements. The infection
      rate for revisions was 19 percent; four patients required explantation after
      revisions. Of 18 patients whose artificial bowel sphincter failed, 9 required a
      stoma. In all, 17 (49 percent) patients have a functional artificial bowel
      sphincter. In Group II fecal incontinence severity scores decreased from a mean
      of 103 preimplant to 59 at one year and to 23 at two or more years (P < 0.001) in
      patients who retained their devices. Quality of life scores improved in all
      patients at six months and at one year (P < 0.01). CONCLUSION: Artificial bowel
      sphincter therapy leads to long-term improved continence and quality of life in
      patients whose implantation is successful. Success rates have not improved in the
      two patient groups, with infection remaining a major challenge. However, once
      successfully established, artificial bowel sphincter function remains stable for
      many years.

PMID- 12794573
TI  - Total anorectal reconstruction with the artificial bowel sphincter: report of
      eight cases. A quality-of-life assessment.
AB  - PURPOSE: The artificial bowel sphincter has been proposed to treat patients with
      fecal incontinence. The good results achieved with this procedure encouraged us
      to use this device for reconversion of patients who previously underwent an
      abdominoperineal resection. METHODS: Between 1999 and 2001, we selected eight
      patients for the total anorectal reconstruction, five for a synchronous
      reconstruction, and three cases for a delayed procedure. One patient was male and
      seven were female. The mean age was 52.6 years. All the patients underwent a
      postoperative manometry and defecography. Continence and quality of life scores
      were also evaluated in the follow-up. RESULTS: The follow-up length ranged from 6
      to 28 months. Manometry assessed a basal pressure with the ABS cuff inflated
      between 58 and 62.2 mmHg. All but one patient achieved a good grade of continence
      with a Wexner score range between 3 and 9. A certain degree of impaired
      evacuation occurred in three patients, but with adequate training this improved
      and did not affect patient's satisfaction. The administered questionnaires
      demonstrated a significant improvement in quality of life scores for stoma
      patients and an elevated quality of life in patients synchronously treated with
      artificial bowel sphincter implant. CONCLUSION: The artificial bowel sphincter is
      a good option for reconstruction of patients previously treated with an
      abdominoperineal resection. The procedure is feasible and safe, without serious
      postoperative complications. The quality of life is improved when the procedure
      is performed in stabilized stoma patients and is acceptable for motivated
      patients synchronously implanted. As compared with electrostimulated
      graciloplasty, the artificial bowel sphincter technique seems to be easier to
      perform and more acceptable for the patients, although the cost of the device is
      still high.

PMID- 12794574
TI  - Endosonographic imaging of anal sphincter injury: does the size of the tear
      correlate with the degree of dysfunction?
AB  - PURPOSE: This study was designed to test the hypothesis that the extent of anal
      sphincter muscle injury as graded at endosonography correlates with the degree of
      functional impairment. METHODS: Three hundred and thirty adults presenting for
      evaluation of fecal incontinence were recruited. Ultrasound was performed with a
      7.5-MHz radial rotating axial endoprobe in the left lateral position. Anal
      sphincter muscle tears were graded on the basis of the degree of circumferential
      involvement (< or >25 percent) and by an assessment of the superoinferior
      longitudinal extent of an external anal sphincter tear. Muscles that demonstrated
      multiple tears, poor visualization, or fragmentation were classed as fragmented.
      Sphincter injuries were correlated with basal and squeeze pressures at manometry,
      pudendal nerve terminal latencies, and the severity of symptoms using the Parks
      Browning clinical score. RESULTS: Patients with an intact external anal sphincter
      had a higher squeeze pressure (mean, 162.6 cm H(2)O) than those with a partial-
      (mean, 125.7 cm H(2)O) or full-length tear (mean, 124.9 cm H(2)O; P < 0.0001).
      There was no significant difference in squeeze pressure between those with
      partial- vs. full-length external anal sphincter tears nor between circumference
      tears < or >25 percent. Basal pressure was significantly lower in those with a
      full-length external anal sphincter tear (47.8 cm H(2)O) vs. an intact external
      anal sphincter (65.7 cm H(2)O; P < 0.001). The basal pressure in those with an
      intact internal anal sphincter was not significantly different from those with
      clearly defined internal anal sphincter tears, and the degree of circumferential
      involvement was also not important in this regard. However, those with a
      fragmented internal anal sphincter had a significantly lower basal pressure than
      other subgroups of internal anal sphincter injuries (P < 0.001). There was no
      association between external or internal anal sphincter status and the mean
      pudendal nerve terminal motor latency, suggesting the patient groups were
      neurologically similar. There was no significant association between external or
      internal anal sphincter status and the severity of reported symptoms. CONCLUSION:
      Correlations between the presence or absence of muscle tears and reduced
      manometric function have been identified. Further grading of tears was of less
      importance. No relationship between muscle injuries and the severity of clinical
      symptoms could be elicited.

PMID- 12794575
TI  - Assessment of the predictive value of a bowel symptom questionnaire in
      identifying perianal and anal sphincter trauma after vaginal delivery.
AB  - PURPOSE: The purpose of this study was to determine whether a postpartum bowel
      habit questionnaire could reliably identify females who had sustained perineal
      and anal sphincter trauma after vaginal delivery. METHODS: A prospective cohort
      design was used to recruit 156 consecutive primigravid females, of whom 134
      delivered vaginally without clinical evidence of a third-degree tear. These 134
      females completed a specific anal continence questionnaire and underwent anal
      endosonography before and after delivery to identify those with postpartum
      deterioration in anal continence and to relate this to sonographic evidence of
      anoperineal trauma. RESULTS: Anal continence deteriorated in 37 females (27.6
      percent) after delivery, 16 of whom (43.2 percent) had sonographic evidence of
      trauma. There was no postpartum deterioration of continence in the remaining 97
      females, 17 (17.5 percent) of whom had sonographic evidence of trauma.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value of the questionnaire for sonographic trauma were 48.5, 79.2, 43.2, and 82.5
      percent, respectively, with corresponding values of 57.1, 75.8, 21.6, and 93.8
      percent for external anal sphincter disruption. CONCLUSION: A bowel-habit
      questionnaire will detect approximately 60 percent of females who sustain
      external sphincter tears after vaginal delivery.

PMID- 12794576
TI  - Modified pouchitis disease activity index: a simplified approach to the diagnosis
      of pouchitis.
AB  - PURPOSE: Pouchitis is the most common complication of ileal pouch-anal
      anastomosis for ulcerative colitis. Our previous study suggested that symptoms
      alone are not reliable for the diagnosis of pouchitis. The most commonly used
      diagnostic instrument is the 18-point pouchitis disease activity index consisting
      of three principal component scores: symptom, endoscopy, and histology. Despite
      its popularity, the pouchitis disease activity index has mainly been a research
      tool because of costs of endoscopy (especially with histology), complexity in
      calculation, and time delay in determining histology scores. It is not known
      whether pouch endoscopy without biopsy can reliably diagnose pouchitis in
      symptomatic patients. The aim of the present study was to determine whether
      omitting histologic evaluation from the pouchitis disease activity index
      significantly affects the sensitivity and specificity of diagnostic criteria for
      pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal
      anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with
      chronic refractory pouchitis and Crohn's disease were excluded. Patients with
      pouchitis disease activity index scores of seven or more were diagnosed as having
      pouchitis. Different diagnostic criteria were compared on the basis of the
      pouchitis disease activity index component scores. Nonparametric receiver
      operating-characteristic curves were used to measure proposed pouchitis scores'
      diagnostic accuracy compared with diagnosis from the pouchitis disease activity
      index. The receiver-operating-characteristic area under the curve measured how
      much these diagnostic strategies differed from each other. RESULTS: Fifty-eight
      consecutive symptomatic patients were enrolled; 32 (55 percent) patients were
      diagnosed with pouchitis. With the use of the pouchitis disease activity index as
      a criterion standard, the use of only symptom and endoscopy scores (modified
      pouchitis disease activity index) produced an area under the curve of 0.995.
      Establishing a cut-point of five or more for diseased patients resulted in a
      sensitivity equal to 97 percent and specificity equal to 100 percent.
      CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index
      offers similar sensitivity and specificity when compared with the pouchitis
      disease activity index for patients with acute or acute relapsing pouchitis.
      Omission of endoscopic biopsy and histology from the standard pouchitis disease
      activity index would simplify pouchitis diagnostic criteria, reduce the cost of
      diagnosis, and avoid delay associated with determining histology score, while
      providing equivalent sensitivity and specificity.

PMID- 12794577
TI  - Factors affecting cost and length of stay associated with the ileal pouch-anal
      anastomosis.
AB  - PURPOSE: The purpose of this study was to evaluate the costs associated with the
      ileal pouch-anal anastomosis procedure and identify those factors that most
      affected or determined such costs. Specifically evaluated were the costs,
      complication rates, and length of stay associated with the ileal pouch-anal
      anastomosis done as a one-stage, two-stage, two-stage modified, or three-stage
      procedure. METHODS: Costs from the hospital accounting database and clinical data
      from retrospective chart review of 135 ileal pouch-anal anastomosis patients from
      a ten-year period were compiled. Overall costs and length of stay (the sum of all
      hospitalizations for all surgeries and any related complications) for each group
      were compared by analysis of variance. Linear regression was used to compute net
      costs and length of stay excluding contributions from other relevant factors such
      as number of operative stages, complications, demographics, and nonelective
      operations. RESULTS: The average overall cost and length of stay of the ileal
      pouch-anal anastomosis ranged from a low of $12,738 and 13.5 days for the one
      stage procedure to a high of $32,758 and 23.9 days for the three-stage pathway.
      Overall costs, length of stay, and incidence of complications increased with the
      number of operations necessary to complete the ileal pouch-anal anastomosis. This
      pattern of increased costs and length of stay with the greater number of stages
      persisted even after demographic and preoperative characteristics were controlled
      for in the analyses. The occurrence of a complication added an average of $9,304
      (P < 0.0001) and 7.4 days to the procedure (P = 0.0002), whereas an urgent
      presentation added an average of $5,258 (P = 0.15) and 6.1 days (P = 0.04).
      CONCLUSIONS: The two most definitive determinants of cost and length of stay
      after ileal pouch-anal anastomosis are complications and number of operative
      stages used to complete the operation. Elective ileal pouch-anal anastomosis
      operations done in the fewest stages with the least complications provide the
      least costly result and the shortest hospital stay. For patients with severe
      disease, the two-stage modified pathway (total abdominal colectomy followed by
      pouch creation without a protecting ileostomy) appears to have fewer
      complications, lower costs, and a shorter length of stay than the traditional
      three-stage pathway.

PMID- 12794578
TI  - Rectal advancement flap repair of rectourethral fistula: a 20-year experience.
AB  - PURPOSE: Several procedures have been described for the management of
      rectourethral fistula. There has been no consensus on the best method of repair.
      The aim of this study was to review our experience with treatment of
      rectourethral fistula, focusing on the outcomes of rectal advancement flap
      repair. METHODS: Data collected included demographics, cause, procedure type,
      presentation, operative details, and morbidity. Telephone follow-up was conducted
      to evaluate functional outcome and quality of life. RESULTS: From 1981 to 2001,
      23 male patients (age, 54 +/- 15 years) were treated for rectourethral fistula.
      Fecal diversion alone was performed in seven patients (30 percent), and urinary
      diversion alone was performed in one patient (4 percent). Both fecal and urinary
      diversion were performed in 12 patients (52 percent), and no diversion was
      performed in 3 (13 percent). Four patients were managed conservatively with
      diversion only. Nineteen patients underwent definitive repair. Rectal advancement
      flap repair was used in 12 (52 percent) of the cases. Postoperative length of
      stay was 4.5 +/- 4 days. Patients were followed up for an average of 31 +/- 33.4
      months. Rectal advancement flap achieved primary closure in 8 (67 percent) of 12
      patients. There were four recurrences. Two patients underwent successful repeat
      repair, for a final success rate of 83 percent. Morbidity associated with rectal
      advancement flap was 8 percent (1/12 patients). Cleveland Global Quality of Life
      score averaged 0.82 +/- 0.13. CONCLUSION: The rectal advancement flap provides an
      effective repair for rectourethral fistula. Successful repair can be achieved in
      a majority of patients with minimal morbidity, short length of stay, and a good
      postoperative quality of life.

PMID- 12794579
TI  - Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with
      ulcerative colitis and primary sclerosing cholangitis: a case control study.
AB  - INTRODUCTION: Patients with ulcerative colitis and primary sclerosing cholangitis
      have an increased risk of developing carcinoma both in the bile ducts and in the
      colon. PURPOSE: To investigate whether this patient group also has an increased
      risk of developing atrophy and neoplasia in the ileal pouch mucosa after
      construction of a pelvic pouch with an ileoanal anastomosis or a continent Kock
      ileostomy. METHODS: Flexible video endoscopic examinations of the ileal pouch
      were performed in 16 patients with ulcerative colitis and primary sclerosing
      cholangitis and in 16 matched patients with ulcerative colitis without sclerosing
      cholangitis. Biopsies were sampled from different locations in the pouch for
      histologic assessment of mucosal atrophy and dysplasia and for flow cytometric
      DNA analysis assessing chromosomal aberrations. RESULTS: The patients with
      sclerosing cholangitis developed moderate or severe atrophy in the pouch
      significantly more often (P < 0.01). Persistent severe mucosal atrophy was
      revealed in eight patients with sclerosing cholangitis and only in two controls.
      One patient with sclerosing cholangitis had high-grade dysplasia in multiple
      locations. Low-grade dysplasia was assessed in three patients with sclerosing
      cholangitis and in two of the controls. DNA aneuploidy was displayed in three
      patients, all with sclerosing cholangitis and dysplasia. All patients with
      neoplastic transformation had a pouch with ileoanal anastomosis and a long pouch
      duration (> 8 years). CONCLUSION: Patients with ulcerative colitis and primary
      sclerosing cholangitis with an ileal reservoir are more prone to developing
      mucosal atrophy in the pouch and seem to have a higher risk of neoplastic
      transformation in the pouch mucosa than patients with ulcerative colitis without
      sclerosing cholangitis.

PMID- 12794580
TI  - Mesorectal lymph nodes: their location and distribution within the mesorectum.
AB  - PURPOSE: Total mesorectal excision is an alternative surgical approach for
      resectable rectal cancer and is associated with favorable results and a low rate
      of local recurrence. Despite the popularity of this technique, few data exist
      regarding the location and distribution of lymph nodes within the rectal
      mesentery. The purpose of this study was to define the distribution, size, and
      location of lymph nodes within the mesorectum and on the pelvic side wall.
      METHODS: Seven fresh cadavers at our institution's Fresh Tissue Dissection
      Laboratory were studied. The rectum, its mesentery, and all fatty tissue from
      both pelvic side walls were removed and placed in a lymph node clearing solution
      for 24 hours. After appropriate dissection, the distribution, size, and location
      of lymph nodes within the rectal mesentery and pelvic side wall tissue were
      documented. RESULTS: A total of 174 lymph nodes were identified (approximately 25
      per patient). The majority (>80 percent) of lymph nodes were smaller than 3 mm in
      diameter. Fifty-six percent of the nodes within the rectal mesentery were located
      in the posterior mesentery, and most were located in the upper two-thirds of the
      posterior rectal mesentery. CONCLUSIONS: The majority of perirectal lymph nodes
      are small. There are few lymph nodes within the mesentery of the lower third of
      the rectum and relatively few in the right and left lateral portions of the
      mesorectum. We confirm that the majority of nodes are located in the proximal two
      thirds of the posterior rectal mesentery. It is possible that removal of these
      nodes is responsible for the superior oncologic results found with total
      mesorectal excision in contrast to more traditional surgical techniques.

PMID- 12794581
TI  - Cyclooxygenase-2 expression in colorectal adenomas.
AB  - PURPOSE: Cyclooxygenase-2 is an important target for nonsteroidal anti
      inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role
      of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase
      2 expression in adenomas with other adenoma characteristics. METHODS:
      Cyclooxygenase-2 expression was evaluated immunohistochemically in 95
      endoscopically resected colorectal adenomas. RESULTS: Cyclooxygenase-2 was
      expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74
      percent (70/95) of adenomas. Expression was related significantly to grade of
      dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic
      regression analysis showed cyclooxygenase-2 expression in adenoma cells to be
      independently associated with grade of dysplasia (P = 0.001). CONCLUSION:
      Observed associations suggest that cyclooxygenase-2 plays an important role in
      progression of the adenoma-to-carcinoma sequence.

PMID- 12794582
TI  - Gene therapy of patient-derived T lymphocytes to target and eradicate colorectal
      hepatic metastases.
AB  - PURPOSE: The overall aim of this study was to develop a novel treatment for
      colorectal cancer based on the use of gene therapy. Genetic modification of T
      lymphocytes has been used to specifically target and kill tumor cell lines
      directly. To test the efficacy of this method with clinically relevant materials,
      this study investigated the potential of T lymphocytes derived from patients with
      advanced colorectal disease to target autologous primary tumor material. METHODS
      T lymphocytes isolated preoperatively were modified genetically with recombinant
      retroviruses encoding CD3zeta-based chimeric immune receptors and were tested for
      functional activity against freshly isolated autologous tumor cells harvested
      from hepatic colorectal metastases. RESULTS: Patient-derived T cells were
      successfully transduced, and chimeric immune receptor expression was confirmed.
      Carcinoembryonic antigen expression on freshly isolated colorectal tumor cells
      was also demonstrated by molecular and immunohistochemical techniques. T cells
      expressing the anticarcinoembryonic antigen receptor were specifically activated
      by coculture with disaggregated or intact, diced tumor, whereas control non
      carcinoembryonic antigen-targeted T-cell populations failed to activate.
      CONCLUSIONS: These results indicate that gene-targeted primary T lymphocytes
      depict specific functional activity against autologous colorectal tumor cells.
      This evidence indicates that chimeric immune receptor-expressing T cells may be
      able to circumvent the mechanisms used by tumor cells to avoid immune cell
      activity in vivo. This study emphasizes the potential of this approach as a
      therapy for carcinoembryonic antigen-expressing primary colorectal tumor and its
      metastases.

PMID- 12794584
TI  - Colorectal motility induction by sacral nerve electrostimulation in a canine
      model: implications for colonic pacing.
AB  - PURPOSE: This study investigated the role of the sacral nerves in the mechanism
      of defecation using adult mongrel dogs. The possibility of designing a colonic
      pacemaker as a new therapeutic device to treat defecation disturbances, such as
      fecal incontinence and severe constipation, is also discussed. METHODS:
      Colorectal motility during spontaneous defecation was monitored with force strain
      gauge transducers implanted in the proximal, distal, and sigmoid colon, rectum,
      and internal anal sphincter. Under general anesthesia, the sacral nerve was
      stimulated electrically, and the colorectal motility response was examined.
      RESULTS: During spontaneous defecation, three characteristic motility patterns
      were observed: 1) giant migrating contractions of the colon were propagated to
      the rectum or anus; 2) the rectum relaxed before the giant migrating contractions
      were propagated; and 3) the internal anal sphincter was relaxed during the
      propagation of the giant migrating contraction. Sacral nerve stimulation elicited
      the following three unique responses: 1) contractile movements were propagated
      from the distal colon to the rectum; 2) a relaxation response was noted in the
      rectum; and 3) the internal anal sphincter exhibited a relaxation response. The
      duration and propagation velocity of the contractile responses and the duration
      of relaxation responses elicited by electrical stimulation of the sacral nerve
      were similar to those that occurred during spontaneous defecation, but their
      amplitudes were smaller. CONCLUSION: The coordinated processes of the colon and
      anorectum during defecation were affected by the sacral nerves. This suggests
      that it is possible to design a colonic pacemaker to control lower colonic and
      rectal movements.

PMID- 12794583
TI  - Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal
      fissure.
AB  - PURPOSE: Nifedipine (administered orally or applied topically) has been effective
      for nonsurgical treatment of anal fissure. We compared the efficacy of nifedipine
      vs. glyceryl trinitrate for chemical sphincterotomy of anal fissure. METHODS: In
      a prospective, double-blind trial, 52 patients suffering from chronic anal
      fissure were randomly and equally allocated to receive either glyceryl trinitrate
      or nifedipine, both applied topically to the perianal region. The end point of
      the study was healing within a predetermined period (6 months). Variables
      assessed included demographic data (age, gender), symptoms associated with the
      fissure, duration of treatment, percentage of healing, untoward effects of
      treatment, pain scores, duration of follow-up, recurrence, and need for
      complementary means of treatment. Descriptive data are presented as mean +/-
      standard deviation and quantal data as percentage. Inference analysis was
      performed using the Student's t-test for the descriptive data and the chi-squared
      or Fisher's exact test for nominal variables. RESULTS: No significant differences
      were recorded with regard to age, gender, symptoms associated with the fissure,
      or duration of treatment. Healing rate was higher (P < 0.04) with nifedipine (89
      percent) as compared with glyceryl trinitrate (58 percent). Treatment side
      effects (headache, flushing) were more frequent (P < 0.01) with glyceryl
      trinitrate (40 percent) as compared with nifedipine (5 percent). Pain scores were
      significantly lower (P < 0.03) on completion of treatment in both groups (3.2 in
      glyceryl trinitrate and 3.4 in nifedipine vs. 6.2 and 6.1, respectively), but did
      not differ between the two groups. Recurrence occurred in 31 percent of patients
      treated with glyceryl trinitrate and 42 percent of those treated with nifedipine
      after a mean period of 18 +/- 3 weeks and 12 +/- 4 weeks, respectively.
      CONCLUSION: Topical application of nifedipine for management of chronic anal
      fissure was more effective and had fewer side effects than topical glyceryl
      trinitrate. Recurrence was frequent with both drugs.

PMID- 12794585
TI  - Diagnosis and monitoring of colorectal cancer by L6 blood serum polymerase chain
      reaction is superior to carcinoembryonic antigen-enzyme-linked immunosorbent
      assay.
AB  - PURPOSE: The aim of this study was to compare carcinoembryonic antigen levels
      with detection of messenger ribonucleic acid coding for the tumor-associated
      antigen L6 in patients with colorectal cancer. Not only are carcinoembryonic
      antigens expressed by the corresponding tumor cell, but the messenger ribonucleic
      acid of tumor-associated antigens, in contrast, is produced exclusively by viable
      tumor cells. METHODS: L6 messenger ribonucleic acid was determined by reverse
      transcription polymerase chain reaction. Carcinoembryonic antigen was measured by
      the enzyme-linked immunosorbent assay technique, with a cutoff value of 40
      microg/l. Blood serum was sampled from 187 patients with colorectal cancer.
      Statistical significance was calculated with the McNemar chi-squared test.
      RESULTS: Preoperatively, 79 percent of patients in all stages were positive for
      L6 messenger ribonucleic acid, whereas only 35 percent had elevated
      carcinoembryonic antigen titers (P < 0.001). In Dukes A tumors, 84.9 percent of
      patients were positive for L6 messenger ribonucleic acid, whereas
      carcinoembryonic antigen was elevated in only 16.9 percent of patients. Only in
      Dukes D tumors did the enzyme-linked immunosorbent assay for carcinoembryonic
      antigen exhibit the same sensitivity as reverse-transcription polymerase chain
      reaction for L6 messenger ribonucleic acid. Recurrence was detected significantly
      earlier by reverse-transcription polymerase chain reaction for L6 messenger
      ribonucleic acid than by enzyme-linked immunosorbent assay for carcinoembryonic
      antigen. CONCLUSION: L6 is more sensitive and precise than carcinoembryonic
      antigen in diagnosing and monitoring colorectal cancer.

PMID- 12794586
TI  - Alpha-fetoprotein-producing carcinoma of the colon: report of a case and review
      of the literature.
AB  - PURPOSE: We describe a rare case of an alpha-fetoprotein-producing carcinoma
      originating in the transverse colon of a 59-year-old Japanese male. METHODS: The
      patient reported an abdominal mass and weight loss. On examination, a tumor of
      the transverse colon and multiple masses in the liver were found. The serum alpha
      fetoprotein level was extremely high (12,873 ng/ml). The patient underwent right
      hemicolectomy and intraoperative biopsy of a liver mass. RESULTS: Histologically,
      the colon cancer was composed of three different components: a well
      differentiated tubular adenocarcinoma, a tubulopapillary carcinoma consisting of
      cells with clear cytoplasms, and a "hepatoid carcinoma." The hepatoid carcinoma
      was composed of large polygonal cells with abundant eosinophilic or clear
      cytoplasms, arranged in a trabecular or solid pattern, and showing marked
      vascular invasion. Immunohistochemically, alpha-fetoprotein was strongly
      expressed, largely in the hepatoid carcinoma and partially in the tubulopapillary
      carcinoma. The liver biopsy specimen showed morphologic and immunohistochemical
      features similar to those of the hepatoid carcinoma of the colon and was
      therefore diagnosed as a metastasis. The patient died of the cancer two months
      after surgery. CONCLUSION: Based on our experience of this patient and a review
      of the literature, alpha-fetoprotein-producing colorectal carcinomas are
      generally associated with a poor prognosis because of the frequent occurrence of
      blood-borne metastases.

PMID- 12794587
TI  - Diverticular abscess of the appendix: report of a case and review of the
      literature.

PMID- 12794588
TI  - Adenocarcinoma of the sigmoid colon seeding a chronic anal fistula: report of a
      case.
AB  - Damaged mucosal sites seem to be vulnerable to tumor cell implantation. We
      describe a case of exfoliated tumor cells from a sigmoid colon cancer seeding a
      long-standing anal fistula. The implications of this finding are reviewed.

PMID- 12794589
TI  - Colporectopexy for obstructed defecation. Do we need anorectal physiology
      studies?

PMID- 12794591
TI  - Breath-hold magnetic resonance cholangiopancreatography in the evaluation of
      malignant pancreaticobiliary obstruction.
AB  - OBJECTIVE: This study was designed to determine the effectiveness of magnetic
      resonance cholangiopancreatography (MRCP) using a breath-hold single-shot fast
      spin echo (SSFSE) technique in imaging patients with malignant biliary and/or
      pancreatic duct obstruction. METHODS: One hundred thirty-one breath-hold MRCP
      studies in patients with malignant pancreatic and/or biliary obstruction were
      evaluated. Pathologic diagnoses included pancreatic cancer, biliary malignancy,
      gallbladder carcinoma, hepatic neoplasms, malignant lymphadenopathy, and
      ampullary carcinoma. Two observers independently reviewed the images in a blinded
      fashion to assess the level of obstruction and the site of underlying tumor.
      RESULTS: The level of obstruction was correctly identified in 104 of 131 cases
      (79%) by observer 1 and in 107 of 131 cases (82%) by observer 2. The site of
      underlying tumor was correctly identified in 113 of 131 cases (86%) by observer 1
      and in 110 of 131 cases (84%) by observer 2. CONCLUSION: Magnetic resonance
      cholangiopancreatography utilizing the SSFSE technique can accurately assess the
      level of obstruction and the site of underlying tumor in patients with malignant
      pancreaticobiliary obstruction, without the risks of cholangiography. This MRCP
      technique allows for visualization of intra- and extraductal anatomy and
      pathology.

PMID- 12794590
TI  - Rare benign and malignant appendiceal lesions: spectrum of computed tomography
      findings with pathologic correlation.
AB  - Although acute appendicitis is the most common disease of the appendix, the
      appendix can be involved by a wide range of diseases. Diseases other than acute
      appendicitis may produce signs and symptoms indistinguishable from those of acute
      appendicitis. Computed tomography (CT) can provide important information for
      diagnosis and evaluation of appendiceal diseases. The various CT and histologic
      features of appendiceal benign and neoplastic diseases are discussed,
      illustrated, and correlated in this article. Radiologists need to understand the
      full spectrum of appendiceal abnormalities, their underlying pathologic changes,
      and associated CT imaging findings.

PMID- 12794592
TI  - Value of magnetic resonance cholangiography in benign and malignant biliary
      stenosis: comparative study with direct cholangiography.
AB  - PURPOSE: Magnetic resonance cholangiography (MRC) is currently under
      investigation for imaging of biliary stenosis. The purpose of this study was to
      evaluate the diagnostic value of MRC compared with direct cholangiography in
      biliary duct diseases, with the exception of biliary-enteric anastomosis. METHOD:
      Forty-nine patients (26 men, 23 women; median age 60 years) with clinically
      suspected bile duct stenosis were prospectively included. Magnetic resonance
      cholangiography was performed within 7 days before direct cholangiography,
      considered to be the gold standard. Stenosis location, extension, and type
      according to Bismuth classification as well as diagnostic presumed causes were
      determined by 2 radiologists and 1 endoscopist. RESULTS: Magnetic resonance
      cholangiography correctly identified the level of biliary ductal obstruction
      compared with direct cholangiography findings in 96% patients. Excellent
      agreement between MRC and direct cholangiography was found for the stenosis
      location (kappa value, 0.89). Sensitivity and specificity of MRC to detect common
      bile duct stenosis were 88% and 100%, respectively. Sensitivity and specificity
      of MRC to detect biliary confluence stenosis were 96% and 93%, respectively.
      Precise location of the lesion according to Bismuth classification was correctly
      evaluated on MRC in 74% of patients (kappa value, 0.64). The overall
      interobserver concordance between radiologists for the level of stenosis was good
      (kappa value, 0.625). In 35 patients with intrahepatic bile ducts dilation
      identified on direct cholangiography, 97% of patients were identified on MRC.
      Moderate concordance between MRC and direct cholangiography was confirmed in the
      evaluation of the surgical management (kappa value, 0.55). CONCLUSION: Magnetic
      resonance cholangiography is able to replace diagnostic direct cholangiography to
      restrict the use of invasive procedures to cases in which therapeutic procedures
      are anticipated or MRC findings are equivocal, especially in biliary tract
      diseases.

PMID- 12794593
TI  - Adult neuroblastoma: radiologic and clinicopathologic features.
AB  - PURPOSE: The purpose of the current study was to define the imaging findings of
      adult neuroblastoma (ANB) and correlate them with clinicopathologic features.
      MATERIALS AND METHODS: The CT scans and MR images of six patients with
      histologically confirmed ANB (mean age, 49 years) were retrospectively analyzed.
      RESULTS: The arising sites of tumors included the retroperitoneum (n = 2), pelvis
      (n = 2), anterior mediastinum (n = 1), and adrenal gland (n = 1). The common CT
      finding was poorly marginated and heterogeneous mass without calcification.
      Cystic components were often found. On contrast-enhanced CT or MR images, tumors
      showed heterogeneous enhancement. On T2-weighted images, all masses demonstrated
      predominantly hyper signal intensity relative to skeletal muscle and the images
      showed heterogeneous appearance with focal areas of high intensity interspersed
      with septations of low signal intensity. Soft tissue masses with bone involvement
      were identified in one case on MR images. The CT findings in one tumor
      originating from mediastinum were similar to those of tumors arising from other
      sites. CONCLUSION: ANB is an uncommon malignancy that often pursues an aggressive
      clinical course, involves multiple sites, and has a poor prognosis. Tumors
      usually manifest on CT or MR images as a poorly demarcated mass mainly in the
      retroperitoneum and pelvis. Imaging studies can depict aggressive characteristics
      and disease extent of ANB.

PMID- 12794595
TI  - Thin section dual-phase multidetector-row computed tomography detection of
      peritoneal metastases in gynecologic cancers.
AB  - PURPOSE: To determine the sensitivity, specificity, and accuracy of multidetector
      row computed tomography (CT) using thin sections and multiplanar reconstruction
      for the detection of peritoneal implants in patients with ovarian cancer. METHOD:
      Seventeen thin section dual-phase multidetector-row CT scans were performed on 17
      women with potential peritoneal metastases from ovarian cancer, which scans were
      then followed by surgery. Axial and multiplanar images from the CT scans were
      reviewed by 2 observers, and the results were compared with the operative and
      clinical notes. RESULTS: Peritoneal metastases were detected by both readers in
      all 7 patients presenting with ovarian cancer and disease at laparotomy.
      Metastases were detected in 5/6 patients with recurrent tumor by observer 1 and
      in 4/6 patients by observer 2. Sensitivity, specificity, and accuracy for
      detecting peritoneal metastases at individual sites in the abdomen and pelvis
      were improved when both axial and multiplanar images were reviewed. Sensitivities
      were highest for the paracolic gutters and infracolic omentum (>70%).
      Approximately 50% of liver and diaphragmatic lesions were detected. Specificities
      approached 100% for all sites and accuracies were >80% for most sites of disease.
      CONCLUSION: The sensitivity, specificity, and accuracy of CT for peritoneal
      metastases in patients is high using thin slices and axial and multiplanar review
      of the data.

PMID- 12794594
TI  - Computed tomographic features of peritoneal carcinomatosis treated by
      intraperitoneal chemohyperthermia.
AB  - PURPOSE: The purpose of this work was to describe the computed tomography (CT)
      features of peritoneal carcinomatosis after surgery combined with intraperitoneal
      chemohyperthermia (IPCH). METHOD: Between 1999 and 2001, 51 consecutive patients
      (33 women and 18 men, with a mean age 45 years) were treated in our institution
      with IPCH for peritoneal carcinomatosis. Patients that were symptomatic (33
      patients) underwent contrast enhanced helical CT of the abdomen and the pelvis
      during the first 15 postoperative days. The CT scans were reviewed
      retrospectively by two blinded observers. Computed tomography abnormalities were
      compared with surgical, biochemical, and clinical findings. RESULTS: None of the
      CT scans were completely normal. Most postsurgical CT findings, including bowel
      and peritoneal thickening (14 and 13 cases, respectively), increased
      intraperitoneal fat density (13 cases), and compartmentalized ascites (8 cases),
      resulted from an inflammatory mesenteric reaction or inflammation of the small
      bowel or the peritoneum and did not require specific treatment. Major
      complications requiring appropriate treatment were intra-abdominal abscesses (5
      cases), hemoperitoneum (5 cases), urinary fistula (2 cases), acute pancreatitis
      (1 case) and abdominal wall abscesses (2 cases). CONCLUSION: Knowledge of early
      CT findings after therapy with surgery combined with IPCH for peritoneal
      carcinomatosis is useful for accurate posttreatment management of these patients.

PMID- 12794596
TI  - Hepatocellular carcinoma: prediction of blood supply from right inferior phrenic
      artery by multiphasic CT.
AB  - OBJECTIVE: Recurrent hepatocellular carcinoma (HCC) often occurs with
      extrahepatic arterial supply (parasitic supply), essentially due to liver
      intraarterial chemoembolization, which could potentially hamper retreatment. The
      right inferior phrenic artery (RIPA) is the most frequent extrahepatic feeding
      artery. We investigated computed tomography (CT) findings of parasitic supply by
      the RIPA, and discuss the utility of multiphasic CT for prediction of parasitic
      supply from RIPA. METHOD: Medical records, CT scans, and angiograms in 20
      patients with HCC fed by RIPA were reviewed. Forty-two patients with HCC but
      without parasitic supply were enrolled as the control group. After injection of
      contrast medium (300 mg I/mL) at a rate of 3 mL/s (total amount, 100 mL), CT
      images were obtained at 30 seconds, 60 seconds, and 150 seconds with scanning
      parameters of 7-mm collimation, 1:1 pitch, and 3.5-mm reconstruction. Two
      radiologists evaluated the previous treatment, patency of the hepatic arteries,
      location of tumors, and detectability and diameter of the RIPA. RESULTS: CT
      demonstrated at least one portion of RIPA in all patients in both groups. The
      distal portions of RIPA were detected on CT more frequently in the parasitic
      group (75%) than in the control group (7.1%). The mean diameter of the RIPA in
      the parasitic group was 2.3 mm (range; 1.6-3.8), and was larger than that of the
      control group (mean; 1.3 mm and range; 0-4.1mm) with statistical significance (P
      < 0.01). CONCLUSIONS: Multiphasic CT could demonstrate the presence of parasitic
      supply to HCCs from RIPA. Visualization of RIPA at the distal portion on CT would
      be a clue of parasitic supply from RIPA.

PMID- 12794597
TI  - Multidetector-row computed tomography with three-dimensional volume rendering of
      pancreatic cancer: a complete preoperative staging tool using computed tomography
      angiography and volume-rendered cholangiopancreatography.
AB  - Volume rendering, a postprocessing computer algorithm that creates three
      dimensional (3D) displays from computed tomography (CT) datasets, can create 3D
      cholangiographic images (volume-rendered cholangiopancreatography, or VRCP) from
      intravenous contrast-enhanced abdominal CT datasets without the use of a biliary
      contrast agent. This article illustrates the utility of VRCP in the setting of
      biliary obstruction due to pancreatic cancer. The 3D renderings of the intra- and
      extrahepatic biliary tree provide valuable information for planning biliary
      drainage, including the location and length of the obstruction as well as the
      relationship of intrahepatic ducts to liver metastases.

PMID- 12794598
TI  - Case report: chronic expanding hematoma in the adrenal gland with pathologic
      correlations.
AB  - We report a case of chronic expanding hematoma in the adrenal gland. Mixed signal
      intensity in a mosaic pattern was seen on T2-weighted images. A focal area
      suggesting a subacute hematoma was also noted. The dynamic CT scan showed
      heterogeneous contrast enhancement in the arterial phase and heterogeneous spread
      of the enhanced area within the tumor. Awareness of this finding may prevent the
      misdiagnosis of a tumor as a neoplastic intratumoral hemorrhage.

PMID- 12794599
TI  - Case report: magnetic resonance imaging of vaginal malignant melanoma.
AB  - We report two cases of vaginal melanoma with magnetic resonance imaging findings.
      The first melanoma was a bilobular polypoid mass with melanotic and amelanotic
      components, which arose from the lateral wall of the vaginal canal. The melanotic
      melanoma showed high signal intensity (SI) on T1-weighted images and low SI on T2
      weighted images, which was not suppressed by a fat-saturated sequence. Another
      melanoma showed a pale brown polypoid mass in the vagina, which revealed
      intermediate SI on T1-weighted images and high SI on T2-weighted images. On fat
      suppressed images, both tumors were more clearly demonstrated with high SI.

PMID- 12794600
TI  - Preoperative CT diagnosis of primary fallopian tube carcinoma in a patient with a
      history of total abdominal hysterectomy.
AB  - Fallopian tube carcinoma is an unusual gynecologic malignancy that is rarely
      diagnosed preoperatively. We report a case of fallopian tube carcinoma occurring
      in a patient who had undergone a hysterectomy many years previously, in whom
      findings on computed tomography and ultrasound were highly suggestive of the
      diagnosis.

PMID- 12794601
TI  - The development and use of a chest phantom for optimizing scanning techniques on
      a variety of low-dose helical computed tomography devices.
AB  - PURPOSE: To develop a chest phantom for determining the optimal scan conditions
      for chest computed tomography (CT) screening. METHODS: The basic structure of the
      phantom is an arms-elevated-positioned anthropomorphic chest phantom. The
      internal structure includes simulated tumors (which are assumed to be the target
      lesions of chest CT screening examinations) placed at the levels of the lung
      apex, the bifurcation of the trachea, and the lung base of both simulated lungs.
      The image contrast of the simulated tumors is taken as the difference in CT value
      and is specified as 1 of 2 target values: Delta270 and Delta100. An opening for
      placement of a dosimeter is provided on the central axis of the phantom. Initial
      field tests were conducted focusing on the scan conditions for chest CT
      screening. RESULTS: Images similar to those obtained in chest CT screening
      examinations and clearly showing pathologic changes were obtained. The dose
      measurement at the center was 2.0 mGy. The diameters of the simulated tumors that
      could be detected were 6 mm for Delta270 and 10 mm for Delta100. CONCLUSION: The
      use of this phantom makes it possible to determine the optimal scan conditions
      for chest CT screening based on objective evaluation criteria.

PMID- 12794602
TI  - Comparison of spirometric-gated and -ungated HRCT in COPD.
AB  - PURPOSE: The purpose of this work was to evaluate feasibility of spirometric
      gated high-resolution computed tomography (HRCT) in patients with chronic
      obstructive pulmonary disease (COPD) and to compare the lung density CT
      measurements obtained with and without spirometric control of lung volume.
      METHOD: Twenty-nine patients with COPD underwent pulmonary function tests and
      spirometric-gated (3 slices at 10% and 90% of vital capacity) and -ungated (12
      slices at maximum expiration and inspiration) HRCT in the same day. Four lung
      density measurements (inspiratory pixel index, expiratory pixel index,
      inspiratory and expiratory mean lung density) derived from gated and ungated
      acquisitions were compared using the nonparametric Wilcoxon test, the line of
      equality, and the Bland and Altman test. RESULTS: The vital capacity measured at
      pulmonary function tests and on the CT table showed a substantial agreement. All
      but one patient completed the gated and ungated examination, but only 8 (28%) of
      28 patients reached the expiratory and inspiratory gating level for CT
      acquisitions at the first attempt. Only the inspiratory mean lung density derived
      from the 3 gated and 12 ungated slices showed borderline agreement. Other CT
      measurements, and notably all those from the 3 gated and ungated scans, acquired
      at the same anatomic level, did not agree. CONCLUSIONS: Although the procedure
      can be difficult for individual patients, spirometric gating significantly
      influences the lung density CT measurements and might improve standardization of
      CT evaluation of COPD.

PMID- 12794603
TI  - Radiological measurement of breast cancer metastases to lung and liver:
      comparison between WHO (bidimensional) and RECIST (unidimensional) guidelines.
AB  - PURPOSE: Radiologic assessment of "response-to-treatment" during clinical trials
      of anticancer drugs has been conventionally based on bidirectional tumor
      measurement. Recently, the revised guidelines were published, which recommended
      unidirectional tumor measurements. The purpose of this study was to compare
      response to treatment between the two measurement techniques in breast cancer
      patients with lung and liver metastases. METHOD: Contrast-enhanced computed
      tomography studies of 86 breast cancer patients who had lung (n = 27) and liver
      (n = 59) metastases and who were enrolled in a phase-III oncology trial were
      evaluated before initiation of treatment and at 6 months after treatment. Lesions
      were measured by subspecialist radiologists on digitized images using electronic
      calipers. The largest diameter of the lesions was extracted from bidimensional
      measurements. Response to treatment was categorized into one of four categories:
      complete response indicating lesion disappearance, partial response indicating
      >30% decrease in tumor diameter, or >50% reduction in tumor area, disease
      progression indicating >20% increase in tumor diameter, or >25% increase in tumor
      area, and stable disease (neither complete response, partial response, nor
      disease progression). Response to treatment between the two measurement
      techniques was compared statistically using the chi2 test. RESULTS: Response to
      treatment was concordant in 76 patients between unidimensional and bidimensional
      measurement techniques. In 5 patients (2 lung and 3 liver metastases) the
      response assessment was improved using unidimensional criteria and in 5 patients
      (2 lung and 3 liver metastases) the response was worse using unidimensional
      guidelines. Thus, the overall response rate was 50% for both unidimensional and
      bidimensional measurement techniques. There was no statistical difference between
      the two techniques. CONCLUSION: Unidimensional measurements are appropriate for
      measuring the size of liver and lung metastases for determining response to
      treatment during clinical testing of oncologic drugs.

PMID- 12794604
TI  - Quantification of mitral valve regurgitation by left ventricular volume and flow
      measurements using electron beam computed tomography: comparison with magnetic
      resonance imaging.
AB  - PURPOSE: This study was designed to evaluate electron beam computed tomography
      (CT) for quantifying mitral regurgitation in comparison with magnetic resonance
      (MR) imaging as a reference method. METHOD: Forty-three patients, among them 33
      with known mitral regurgitation, underwent electron beam CT and MR imaging. Total
      left ventricular stroke volume (TSV), antegrade stroke volume (ASV), and mitral
      regurgitation volume (MRV) and fraction (MRF) were determined and compared
      between the two modalities. Additionally electron beam CT measurements were
      compared with the corresponding echocardiographic findings. RESULTS: Significant
      differences between electron beam CT and MR imaging were found for measurements
      of TSV and MSV but not for ASV and MRF. There was a close linear correlation
      between both modalities for all parameters. Furthermore, there was good agreement
      between electron beam CT and echocardiography, although electron beam CT shows a
      tendency to overestimate mitral regurgitation slightly. CONCLUSION: The results
      indicate that electron beam CT offers an additional procedure for quantifying
      mitral regurgitation and that it may be used as an alternative to MR imaging.

PMID- 12794605
TI  - Comparative study with a moving heart phantom of the impact of temporal
      resolution on image quality with two multidetector electrocardiography-gated
      computed tomography units.
AB  - OBJECTIVE: The objective of this study was to compare the temporal resolution
      related image quality of electrocardiography-gated images acquired with two
      multidetector computed tomography (CT) units with a moving heart phantom, at
      similar fixed heart rates, using half-scan and multisector acquisition modes.
      METHODS: An adjustable moving heart phantom (Limbsandthings, Horfield, Bristol,
      UK) was used. Specific heart rates (47, 55, 64, 66, 69, and 73 beats per minute
      [bpm]) were chosen. On a General Electric CT unit (LightSpeed Plus; General
      Electric Medical Systems, Milwaukee, WI), retrospective half-scan and multisector
      mode protocols were performed. On a Siemens CT unit (Somatom Volume Zoom;
      Siemens, Forchheim, Germany), a retrospective half-scan mode was performed at 47,
      55, and 64 bpm, and a two-sector mode was performed at 66, 69, and 73 bpm.
      Reformatted maximum intensity projection images were qualitatively compared and
      related to their temporal resolution. RESULTS: Half-scan mode protocols provided
      similar good results with both CT units up to 55 bpm. The two-sector mode
      improved image quality compared with the half-scan mode. High temporal resolution
      with the multisector mode provided the best results. CONCLUSION: For coronary
      artery imaging, acquisition protocols that provide the highest temporal
      resolution are mandatory. The multisector mode is one technique that allows high
      temporal resolution but may be clinically inappropriate at heart rates below 65
      bpm or when heart rate variation is observed during scan time.

PMID- 12794606
TI  - Evaluation of the deep venous system in patients with suspected pulmonary
      embolism with multi-detector CT: a prospective study in comparison to Doppler
      sonography.
AB  - OBJECTIVE: This prospective study was done to evaluate the ability of indirect
      multidetector row CT venography (CTV) in detecting deep venous thrombosis of the
      pelvis and the thighs in comparison with Doppler sonography in patients with
      suspected pulmonary embolism (PE). METHODS: Forty-one patients with suspected PE
      were included, and CTV (collimation 4 x 2.5 mm, table feed 12.5 mm, 120 kV, eff.
      mAs 165) from the iliac crest to the knees was done after CT angiography (CTA) of
      the pulmonary arteries. Doppler sonography was performed within 24 hours. Applied
      radiation doses were estimated using the PC program WinDose. RESULTS: PE was
      diagnosed in 20 patients with additional DVT in 11 patients. The CTV has a
      sensitivity of 100%, specificity of 96.6%, a positive and negative predictive
      value of 91.7% and 100%, respectively. The median cumulative effective dose for
      CTV was 8.26 mSv with a gonadal dose of 3.87 mSv. Changing the CTV protocol to a
      collimation of 4 x 5 mm with a 25 mm table feed could reduce the dose by
      approximately 11% (p < 0.05) to 7.25 mSv and 3.35 mSv, respectively. CONCLUSION:
      CTV is a safe and quick diagnostic tool for detecting DVT in patients with
      suspected PE. Due to the relevant increase in radiation dose, the indication has
      to be considered very carefully.

PMID- 12794607
TI  - Case report: diffusion-weighted MRI in anterior spinal artery stroke of the
      cervical spinal cord.
AB  - The authors present a case of anterior spinal artery stroke demonstrated by
      diffusion-weighted MRI (DWI) using single-shot echo-planar imaging. DWI clearly
      demonstrated hyperintensity with a decreased apparent diffusion coefficient (ADC)
      at 26 hours after onset. At 28 days, there was persistent hyperintensity with an
      increased ADC, corresponding to T2-weighted hyperintensity in the whole spinal
      gray matter at the C2-C7 vertebral level. DWI provided satisfactory images and
      was helpful for diagnosing and evaluating anterior spinal artery stroke.

PMID- 12794608
TI  - Case report: spinal cord infarction demonstrated on diffusion-weighted MR imaging
      with a single-shot fast spin-echo sequence.
AB  - We describe the diffusion-weighted (DW) MR imaging findings in three cases of
      spinal cord infarction using a recently developed single-shot fast spin-echo
      (SSFSE) technique. The SSFSE-DW MR images, which were obtained 20 hours, 3 days,
      and 18 days, respectively, after the ischemic event, demonstrated conspicuous
      areas of hyperintensity in the affected portions. Follow-up DW MR images,
      obtained in two of the patients at 17 days and 3 months, respectively, showed
      persistent decreased apparent diffusion coefficient values. SSFSE-DW imaging of
      the spinal cord may provide additional information for assessment of ischemic
      changes.

PMID- 12794609
TI  - Case report: hypoglycemia and diffusion-weighted imaging.
AB  - The effect of severe hypoglycemia on the brain is well known, ranging from
      alterations of mental status to profound coma and death. We describe a case of
      global diffusion abnormalities eventually resulting in death. This otherwise
      healthy patient presented with seizures and a serum glucose level less than 20
      mg/dL. Testing suggested that the hypoglycemia was likely caused by exogenous
      insulin or perhaps insulin receptor antibodies. Magnetic resonance imaging on the
      day after admission showed regions of restricted diffusion in the temporal and
      occipital lobes as well as in the basal ganglia. Despite the large body of
      literature concerning the pathophysiology of hypoglycemia and its clinical
      implications, little is known regarding its radiologic correlations.

PMID- 12794611
TI  - Fast magnetic resonance imaging in steady-state precession (true FISP) in the
      prenatal diagnosis of a congenital brain teratoma.
AB  - Teratomas are the most common congenital intracranial tumor. Although fetal
      magnetic resonance (MR) imaging is becoming more popular for prenatal diagnosis,
      only 2 cases of congenital intracranial teratoma have been reported, and these
      cases relied on half-Fourier single-shot turbo spin echo (HASTE) imaging. We
      report the first known case of congenital intracranial teratoma diagnosed by
      means of a fast imaging in steady-state precession (true FISP) MR sequence. True
      FISP can be obtained in almost 20 seconds and provides superior contrast
      resolution compared with HASTE.

PMID- 12794610
TI  - Case report: cushing disease caused by an ectopic intracavernous pituitary
      microadenoma: case report and review of the literature.
AB  - Despite increasing performance of pituitary imaging, adrenocorticotropic hormone
      (ACTH)-secreting pituitary adenomas are often difficult to identify because of
      their small size and variable location. We present a case of ACTH-dependent
      Cushing syndrome in which the demonstration of the cavernous sinus localization
      of a microadenoma was made by magnetic resonance imaging (MRI). Ectopic pituitary
      microadenomas have been described only in a few reports, and the current case
      report is the first to our knowledge to illustrate clearly the intracavernous
      localization of the microadenoma.

PMID- 12794612
TI  - Diffusion MR imaging of giant cell tumors in tuberous sclerosis.
AB  - Giant cell tumors were studied by diffusion MR imaging in three patients with
      tuberous sclerosis. Diffusion MR imaging was performed on a 1.5-T unit with a
      gradient strength of 30 mT/m. b = 1000 seconds/mm2 images, and apparent diffusion
      coefficient (ADC) maps were studied. ADC values were recorded from ADC maps with
      particular care to obtain the values from the noncalcified regions of the giant
      cell tumors. ADC values of the normal brain parenchyma and hamartomas were also
      recorded by multiple evaluations. The ADC values in all three giant cell tumors
      (0.78, 0.92, and 0.92 x 10-3mm2/s) were within the ranges of the normal brain
      parenchyma (0.62-1.04 x 10-3mm2/s), and they were prominently less than those of
      parenchymal hamartomas (1.18-1.86 x 10-3mm2/s). The finding of ADC values of the
      noncalcified portions of the giant cell tumors being identical to those of normal
      brain parenchyma is consistent with the presence of normal molecular motion of
      water, hence relatively normal tissue integrity within these tumors. This was
      likely a reflection of benignity of these slowly growing tumors.

PMID- 12794613
TI  - Additional value of magnetic resonance with spin echo T1-weighted imaging with
      fat suppression in characterization of soft tissue tumors.
AB  - OBJECTIVE: The aim of the study was to describe the signal intensity (SI)
      behavior of soft tissue tumors (STT) on spin echo (SE) T1 weighted images (WI)
      with fat suppression (FS) and to assess its additional value in tissue
      characterization. METHODS: MRI signal characteristics of 53 histological proven
      STT were discussed. Signal intensity behavior of STT could be classified in 4
      types, representing specific tissues or tissue components. Type 1 was defined as
      low SI on both SE T1-WI and SE T1-WI with FS. Type 2 was defined as high SI on
      both sequences. Type 3 consisted of high SI on T1-WI and low SI on T1-WI with FS.
      Type 4 was defined as SI comparable with SI of normal muscle on T1-WI and SI
      higher than normal muscle on T1-WI with FS. The additional information concerning
      contrast enhancement is described. RESULTS: Type 1 SI behavior was noted in
      fibrous lesions, in hemosiderotic components, cysts, and myxoma. Type 2 was noted
      in lesions containing methemoglobin or melanin. Type 3 was specific for fatty
      tissue. Type 4 was noted in highly cellular parts and in lesions of vascular
      origin. The use of SE T1-WI with FS improved lesion conspicuity on T1-WI.
      CONCLUSIONS: E T1-WI with FS has additional value in the characterization of
      fibrous and hemosiderotic parts from cellular parts of lesions. It gives more
      confidence in characterization of neurogenic tumors and hemangioma's. Presence of
      methemoglobin and melanin are clearly discriminated from fatty tissue. Tumor
      conspicuity and inhomogeneity evaluation is improved. The use of SE T1-WI FS not
      only improves tumor conspicuity, but as tumor homogeneity and SI are important
      parameters in staging and characterization of STT, the use of SE T1-WI with FS
      will certainly be helpful. This may obviate the need for gadolinium
      administration.

PMID- 12794614
TI  - Two-dimensional excitation short echo time chemical shift imaging at 0.5 tesla.
AB  - Detection of short T2 metabolites such as glutamate and glutamine (glx) in the
      brain can be improved by minimizing the echo time (TE) of the pulse sequence. By
      combining two dimensions of localization during a single radiofrequency (RF)
      pulse, an elliptic excitation chemical shift imaging sequence (EECSI) that
      further reduces TE by a factor of 2 relative to a TE-optimized point resolved
      spectroscopy sequence chemical shift imaging sequence was developed. An
      additional set of outer volume saturation pulses is included to minimize the
      contamination from scalp and marrow space lipids. The sequence runs with
      conventional gradient hardware (1 G/cm, 17 T/m/s slew rate) at 0.5 T. The
      increase in the fitted areas of beta,gamma multiplet of glutamate and glx in a
      brain-mimicking phantom was by a factor of 1.66. In the thalamus of healthy
      volunteers, glx was increased by 1.44. Combined with the field strength-related
      improvements in glutamate and glx detection previously demonstrated at 0.5 T,
      EECSI offers further improvements for imaging glutamate and glx in vivo.

PMID- 12794615
TI  - Reproducibility of metabolite concentration evaluated by intraclass correlation
      coefficient using clinical MR apparatus.
AB  - OBJECTIVE: The purpose of this study was to evaluate the reproducibility of in
      vivo quantitative proton MR spectroscopy (MRS) by repeated-measure analysis of
      variance and intraclass correlation coefficient (ICC) including assessment of
      both inter- and intrasubject variation. METHODS: The concentration of metabolites
      was quantified using long-TR and short-TE stimulated-echo acquisition mode
      sequences with a quadrature head coil. All preparation procedures for MRS
      measurement except volume of interest determination were done by an automatic
      preparation scanning system equivalent to a clinical setting. Analyses were
      conducted by an LCModel running based on our original basis set by two different
      reference methods. RESULTS: The ICC showed a good correlation (r = 0.61-0.99) in
      any metabolite and almost the same value between the two different reference
      methods, but the concentration of myoinositol had a large intersubject variation.
      CONCLUSION: Our results suggest that the reproducibility of quantified metabolite
      concentration is acceptable in the clinical setting regardless of the reference
      method, although quantified values may have different intersubject variations.

PMID- 12794618
TI  - The role of total mesorectal excision in the management of rectal cancer.
AB  - BACKGROUND: Total mesorectal excision (TME) was described 20 years ago and is now
      being established as the therapeutic gold standard for middle and lower third
      rectal cancers in a number of countries worldwide. METHODS: The authors reviewed
      published data regarding TME since its first description in 1982. Emphasis was
      placed on basic principles, achievable recurrence rates, evidence for use of
      adjunctive strategies, and the potential of TME. RESULTS: Local recurrence rates
      following TME approximate 6.6% from published series, accounting for more than
      5,000 patients. The available evidence for TME is largely composed of
      retrospective series, although benefits of TME compare favorably to established
      conventional controls. Recent studies have clarified the benefit of adjunctive
      radiotherapy with TME. There is considerable scope for development of TME within
      the minimal access setting, providing first principles are observed. CONCLUSIONS:
      Despite initial controversy, TME is now a feasible, reproducible, adjunctive
      surgical therapy in the management of rectal cancer.

PMID- 12794617
TI  - Current and evolving strategies for colorectal cancer screening.
AB  - BACKGROUND: Colorectal cancer is a major cause of cancer mortality and morbidity.
      Screening can potentially prevent most colorectal cancers by detection and
      removal of precursor adenomas. METHODS: The literature and clinical practice
      guidelines are reviewed, with an emphasis on advances of the last 10 years and
      evolving screening methods. RESULTS: Colonoscopy has come to be used for
      screening in persons at average risk for colorectal cancer because of the
      comparative ineffectiveness of other methods, although these methods continue to
      be recommended. Virtual colonoscopy and fecal DNA testing are emerging
      technologies with promise to be more effective than fecal occult blood testing or
      sigmoidoscopy in selecting those persons who should undergo colonoscopy. Next to
      age, family history is the most common risk factor for colorectal cancer and one
      that warrants more aggressive screening and, in some instances, genetic
      counseling and testing. Hereditary nonpolyposis colorectal cancer accounts for as
      many as 1 in 20 colorectal cancers, but to take advantage of recent advances in
      genetic testing for this disorder, a high level of clinical suspicion must be
      maintained. CONCLUSIONS: If we are to reduce mortality and morbidity from
      colorectal cancer, practicing clinicians need to be aware of current and evolving
      strategies for colorectal screening, and assertively recommend the appropriate
      strategy to their patients.

PMID- 12794619
TI  - Methods and results of sphincter-preserving surgery for rectal cancer.
AB  - BACKGROUND: Sphincter preservation is the goal in the treatment of rectal cancer
      and should be considered in all patients with an intact sphincter. Sphincter
      preservation for tumors of the upper rectum is easily achieved, but surgical
      management of cancer of the mid and lower third of the rectum continues to
      evolve. Several recent advances may influence future treatment strategies.
      METHODS: We reviewed the literature to identify the current methods of sphincter
      preserving surgery and their oncologic and functional results. RESULTS:
      Proctectomy with total mesorectal excision reduces the incidence of local
      recurrence to less than 10% while preserving genitourinary function. The use of
      preoperative radiotherapy may further diminish the risk of local recurrence. In
      selected patients, partial resection of the anal sphincter may avoid definitive
      colostomy without compromising oncologic outcome. In contrast, the role of local
      resection of rectal cancer remains controversial. Restoration of continuity by
      means of a colonic reservoir reduces stool frequency and urgency and improves
      continence when compared to a straight coloanal anastomosis. The transverse
      colpoplasty pouch may allow pouch construction in patients in whom it is
      currently impossible, but long-term follow-up is not yet available. CONCLUSIONS:
      Sphincter-preserving surgery is possible for the majority of patients with rectal
      cancer. Optimal functional results may be obtained by a nerve-sparing operative
      technique and by use of a colonic reservoir for reconstruction following
      resection of mid or low rectal cancers.

PMID- 12794621
TI  - Metastatic colorectal cancer: systemic treatment in the new millennium.
AB  - BACKGROUND: Colorectal cancer (CRC) is common in North America. Metastatic
      disease is present at diagnosis in 30% of the patients, and approximately half of
      early-stage patients will eventually present with metastatic disease. Until
      recently, few chemotherapy options were available to treat metastatic CRC.
      METHODS: The authors review the results of recent clinical trials and the design
      of ongoing trials in the management of patients with metastatic colorectal
      cancer. RESULTS: Fluorouracil (5-FU) with leucovorin (LV) modulation has a
      marginal but positive effect on survival in those patients. The recent
      incorporation of irinotecan (CPT-11) and oxaliplatin for the management of
      advanced CRC has generated further improvement in survival. The development of
      oral fluoropyrimidines, mimicking continuous infusion 5-FU, is convenient. In
      randomized trials, capecitabine was equally effective to bolus 5-FU and LV in the
      management of metastatic CRC. CONCLUSIONS: Recently completed or ongoing clinical
      trials to study novel targeting agents have initiated a new era of drug
      development. Anti-angiogenesis drugs, tyrosine kinase inhibitors, and epidermal
      growth factor blockers are among this new generation of agents with encouraging
      preliminary data. Randomized trials will determine the impact of these newer
      agents on survival and quality of life of patients with metastatic CRC.

PMID- 12794620
TI  - Lymphatic mapping and sentinel node analysis to optimize laparoscopic resection
      and staging of colorectal cancer: an update.
AB  - BACKGROUND: Laparoscopic colectomy for colorectal cancer (CRC) has been
      criticized because of the potential for inadequate nodal dissection and
      incomplete staging. Lymphatic mapping (LM) and sentinel lymph node (SLN) analysis
      can improve the accuracy of staging in open colectomy, but its utility during
      laparoscopic colectomy is unknown. METHODS: Between 1996 and 2002, 30 patients
      with clinically localized colorectal neoplasms or premalignant polyps underwent
      subserosal or submucosal injection of isosulfan blue dye via a colonoscope, via a
      percutaneously inserted spinal needle, or through a hand port. Blue-stained
      lymphatics were visualized through the laparoscope and followed to the SLN, which
      was tagged. The colectomy was completed in standard fashion. All lymph nodes were
      stained by hematoxylin and eosin, and multiple sections of each SLN were examined
      by immunohistochemical (IHC) staining using cytokeratin antibody. RESULTS: An SLN
      was identified laparoscopically in all patients. The SLN accurately predicted the
      tumor status of the nodal basin in 93% of cases. In 8 cases (29%), an unexpected
      lymphatic drainage pattern altered the extent of mesenteric resection, and in 4
      cases (14%), tumor deposits were identified only by IHC and limited to the SLN.
      CONCLUSIONS: This study, which updates a preliminary report (Am Surg. 2002;68:561
      565) confirms that SLN mapping during laparoscopic colon resection can alter the
      margins of resection and may improve staging by allowing a focused pathologic
      examination of the SLN, although direct comparison with the "gold standard" of
      open CRC with adequate lymphadenectomy will be required. Better ultrastaging of
      CRC lymph nodes may more accurately assign patients to prospective protocols to
      assess the significance of nodal micrometastases or isolated tumor cells.

PMID- 12794622
TI  - Central nervous system metastases from primary epithelial ovarian cancer.

PMID- 12794623
TI  - A call to molecular arms answered.

PMID- 12794624
TI  - Long-term prognosis after a normal exercise stress Tc-99m sestamibi SPECT study.
AB  - BACKGROUND: Patients with a normal stress technetium 99m sestamibi study were
      shown to have a favorable outcome at intermediate-term follow-up. However, long
      term survival has not been studied. The aim of this study was to evaluate the
      incidence and predictors of mortality and cardiac events at long-term follow-up
      after a normal exercise stress sestamibi study. Methods and results We studied
      218 patients (mean age, 53 +/- 10 years, 108 men) who had normal myocardial
      perfusion assessed by Tc-99m sestamibi single photon emission computed tomography
      at rest and during symptom-limited bicycle exercise stress test. Endpoints during
      a follow-up period of 7.4 +/- 1.8 years were hard cardiac events (cardiac death
      and nonfatal myocardial infarction) and all-cause mortality. During follow-up, 13
      patients died of various causes (cardiac death in 1 patient). Ten patients had
      nonfatal myocardial infarction (a total of 11 hard cardiac events). By
      multivariate analysis, independent predictors of cardiac events were history of
      coronary artery disease (chi(2) = 5, P =.03) and lower exercise heart rate
      (chi(2) = 12, P =.001). Independent predictors of all-cause mortality were age
      (chi(2) = 4, P =.05) and exercise heart rate (chi(2) = 5, P =.03). The annual
      mortality rate was 0.6% in the first 5 years and 1.8% between the sixth and
      eighth years. The annual hard cardiac event rate was 0.7% in the first 5 years
      and 1.5% between the sixth and eighth years. Receiver operating characteristic
      curves identified an exercise heart rate lower than 130 beats/min as the cutoff
      value that separated patients with regard to their risk for mortality and hard
      cardiac events. CONCLUSIONS: It is concluded that the annual mortality and
      cardiac event rate is less than 1% during 5-year follow-up after a normal
      exercise sestamibi study. Therefore repeated testing would not be required unless
      there is a change in symptoms. Follow-up should be closer in patients with a
      history of coronary artery disease and in those who fail to achieve an exercise
      heart rate of 130 beats/min or greater.

PMID- 12794625
TI  - Simultaneous assessment of myocardial perfusion and function during mental stress
      in patients with chronic coronary artery disease.
AB  - BACKGROUND: Mental stress (MS) is an important provocateur of myocardial ischemia
      in many patients with chronic coronary artery disease. The majority of laboratory
      assessments of ischemia in response to MS have included measurements of either
      myocardial perfusion or function alone. We performed this study to determine the
      relationship between alterations in perfusion and ventricular function during MS.
      Methods and results Twenty-eight patients with reversible perfusion defects on
      exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent
      simultaneous technetium 99m sestamibi single photon emission computed tomography
      (SPECT) MPI and transthoracic echocardiography at rest and during MS according to
      a mental arithmetic protocol. In all cases the MS study was performed within 4
      weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia.
      SPECT studies were analyzed visually with the use of a 13-segment model and
      quantitatively by semiautomated circumferential profile analysis. Echocardiograms
      were graded on a segmental model for regional wall motion on a 4-point scale. Of
      28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction
      develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had
      regional or global left ventricular dysfunction develop, and 3 (11%) had both
      perfusion defects and left ventricular dysfunction develop. The overall
      concordance between perfusion and function criteria for ischemia during MS was
      only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had
      new regional wall motion abnormalities and 4 had a global decrement in function.
      In patients with MS-induced ischemia by SPECT, the number of reversible perfusion
      defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0
      vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether
      patients were divided on the basis of perfusion defects or left ventricular
      dysfunction during MS. CONCLUSIONS: These data indicate the feasibility of
      simultaneous assessment of perfusion and function responses during MS. Flow and
      function responses to MS are frequently not concordant. These data suggest that
      MS-induced changes in perfusion may represent a different phenomenon than MS
      induced changes in left ventricular function (either globally or regionally).

PMID- 12794626
TI  - Reduction of coronary flow reserve in areas with and without ischemia on stress
      perfusion imaging in patients with coronary artery disease: a study using oxygen
      15-labeled water PET.
AB  - BACKGROUND: Myocardial perfusion single photon emission computed tomography
      (SPECT) occasionally fails to detect coronary stenosis in patients with coronary
      artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15
      labeled water in areas with and without ischemia on technetium 99m tetrofosmin
      stress perfusion SPECT in patients with angiographically documented CAD. METHODS
      AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal
      subjects were studied. Baseline myocardial blood flow (MBF) and MBF during
      hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(
      1). min(-1)) were determined with the use of O-15-labeled water positron emission
      tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was
      performed for comparison. On the basis of the results of coronary angiography and
      SPECT, coronary segments were divided into 3 types: segments with coronary
      stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16),
      segments with coronary stenosis without a perfusion abnormality (group B, n =
      42), and remote segments with no coronary stenosis or perfusion abnormality
      (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in
      group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in
      group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001).
      CFR in group B was lower than in group C (P <.02) and in normal segments (P
      <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS:
      Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas
      without a perfusion abnormality and with coronary stenosis, lowering of CFR was
      intermediate between the areas with a perfusion abnormality and remote segments.
      Moreover, CFR was slightly, but significantly, lower in remote segments in
      patients with CAD compared with normal segments.

PMID- 12794628
TI  - The impact of adjunctive adenosine infusion during exercise myocardial perfusion
      imaging: Results of the Both Exercise and Adenosine Stress Test (BEAST) trial.
AB  - BACKGROUND: Failure to achieve an adequate heart rate limits the sensitivity of
      exercise myocardial perfusion imaging (MPI) for the detection of coronary artery
      disease. In addition, it is often not possible to discontinue medications that
      may blunt the heart rate response to exercise, because of conditions such as
      hypertension or angina. However, if pharmacologic stress testing is performed,
      the ability to assess functional capacity is lost. Accordingly, we developed a
      protocol that incorporates adenosine stress with symptom-limited exercise.
      METHODS AND RESULTS: As part of a multicenter study, 35 patients were enrolled
      prospectively and underwent both exercise MPI and exercise MPI with a 4-minute
      adenosine infusion on a separate day. Technetium 99m sestamibi was injected at or
      near peak exercise (exercise only) and at 2 minutes into the adenosine infusion
      (combined exercise and adenosine). The perfusion images were interpreted in a
      blinded fashion. The combined adenosine and exercise protocol was well tolerated.
      The summed stress scores and summed difference scores were greater in the
      exercise-plus-adenosine group than in the exercise-only group (10.0 vs 8.5, P
      =.02, and 4.9 vs 3.3, P =.002, respectively). Exercise time was slightly but
      significantly less with the exercise-plus-adenosine protocol (8 minutes 46
      seconds vs 8 minutes 11 seconds, P =.027). CONCLUSION: A protocol combining 4
      minutes of adenosine infusion with symptom-limited exercise was safe and well
      tolerated. Furthermore, this protocol resulted in a greater amount of myocardial
      ischemia detected on MPI while allowing for the assessment of functional
      capacity. A combined exercise and adenosine protocol may be a useful test for
      patients undergoing MPI who are unlikely to achieve an adequate chronotropic
      response.

PMID- 12794627
TI  - A comprehensive strategy for the evaluation and triage of the chest pain patient:
      a cost comparison study.
AB  - BACKGROUND: Our objective was to determine the cost-effectiveness of a
      comprehensive, risk-based triage system, composed of multiple critical pathways,
      with the use of early myocardial perfusion imaging (MPI) in low-risk patients. We
      found previously that a chest pain evaluation system that uses MPI in low-risk
      patients was safe and effective, but the cost-effectiveness of this approach was
      not studied. METHODS AND RESULTS: We compared two groups. The Acute Cardiac Team
      (ACT) group (n = 874) was assigned prospectively to 1 of 4 risk levels by
      emergency department (ED) physicians. Level 1, 2, and 3 patients were admitted;
      level 4 patients were evaluated in the ED. Level 3 and 4 patients underwent ED
      MPI. The control group (n = 713) represented consecutive patients evaluated in
      the prior year according to standard care and assigned retrospectively to an ACT
      level based on the presenting electrocardiographic and clinical data. Record and
      hospital administrative data were assessed for clinical variables, outcomes,
      lengths of stay, and all expenses incurred within 30 days of the index visit. The
      baseline characteristics of the two groups were similar, including age, sex,
      myocardial infarction prevalence, and 30-day revascularization rates within each
      level or between the two groups. Mean costs per encounter were reduced for the
      ACT patients for each level, which was significant when all patients were
      compared ($5,030 +/- $7,081 vs $6,044 +/- $10,432, P =.02). Use of MPI in the low
      risk patients was associated with reduced costs (level 3, $4,958 +/- $4,948 vs
      $5,051 +/- $7,036; level 4, $1,529 +/- $2,664 vs $1,794 +/- $6,854) and was
      associated with a significantly lower angiography rate and shorter length of
      stay. CONCLUSIONS: Implementation of a comprehensive strategy for chest pain
      evaluation and triage reduced overall costs for patients with chest pain on
      presentation. Acute MPI in the ED setting did not increase net cost.

PMID- 12794629
TI  - Gated fluorine 18 fluorodeoxyglucose positron emission tomography: determination
      of global and regional left ventricular function and myocardial tissue
      characterization.
AB  - BACKGROUND: Our objectives were to investigate the accuracy of global and
      regional left ventricular (LV) function parameters determined from gated fluorine
      18 deoxyglucose (FDG) positron emission tomography (PET) and to determine whether
      this approach complements viability imaging data for tissue characterization.
      Nongated FDG-PET is a clinical standard for viability imaging, but LV function is
      often determined with other techniques, which increases patient burden,
      expenditure, and co-registration errors. Better tissue characterization may be
      achieved if data were acquired with one test. Methods and results Forty-eight
      patients with LV dysfunction (including 35 with ejection fraction [EF] </=35%)
      underwent perfusion/FDG imaging with gating of the FDG images and radionuclide
      angiography (RNA) 6 +/- 6 days apart. Regional function (wall motion/thickening)
      and viability pattern (normal, mismatch, nontransmural scar, and transmural scar)
      were determined for 301 segments. Global EFs from FDG-PET (29.3% +/- 11.5%) and
      RNA (31.1% +/- 10.4%) were well correlated: EF(FDG-PET) = 0.91 x EF(RNA) + 0.91
      (r = 0.83, P <.00001). Regional wall motion concordance between PET and RNA with
      three wall motion scores was 67% with moderate agreement (kappa = 0.50, P <.001).
      PET viability was also determined for each segment. The relative frequency of
      normal motion compared with abnormal motion decreased with worsening viability
      classification. Of the normal segments, 96 of 139 (69%) had reduced wall motion,
      suggesting repetitively stunned myocardium. Segments classified as normal or
      mismatch had a higher frequency of normal wall thickening (65% and 52%) than wall
      motion (31% and 17%). No segments classified as transmural scar exhibited normal
      wall thickening. CONCLUSION: Gated FDG-PET accurately measures global LV
      function. Regional function can also be determined with reasonable accuracy. This
      approach also provides precise co-registration of function with metabolic
      information and thus improved tissue characterization of the myocardium. Gated
      FDG-PET has the potential to assist in optimizing management of this patient
      population.

PMID- 12794630
TI  - Cardiac sympathetic nerve activity in patients with hypertrophic cardiomyopathy
      with malignant ventricular tachyarrhythmias.
AB  - BACKGROUND: Malignant ventricular tachyarrhythmia (VT) and sudden death are
      serious events in hypertrophic cardiomyopathy (HCM). However, the pathophysiology
      of this condition is not well understood. The objective of this study was to
      evaluate the relationship between cardiac sympathetic nerve activity and the
      occurrence of VT in HCM patients. Methods and results We studied iodine 123
      metaiodobenzylguanidine scintigraphy and 24-hour ambulatory electrocardiographic
      monitoring in 44 HCM patients, 15 with VT (group A) and 29 without VT (group B).
      With planar I-123 metaiodobenzylguanidine imaging, the heart-to-mediastinum ratio
      for early and delayed acquisition and washout rate were calculated. Polar maps of
      left ventricular myocardium were divided into 20 segments, and the SD of uptake
      and washout rate in 20 segments were calculated as indices of regional variation.
      The global washout rate was significantly higher in group A than in group B (26.8
      +/- 6.4% vs 17.4 +/- 5.7%, P <.0001), although other parameters including
      heterogeneity indices did not differ. The logistic multiple regression analysis
      also determined that washout rate was the most powerful predictor of VT in
      patients with HCM. CONCLUSIONS: The occurrence of malignant VT in HCM may be
      associated with global cardiac sympathetic nerve activity rather than with the
      heterogeneity of this activity.

PMID- 12794631
TI  - Metabolic and molecular basis of insulin resistance.

PMID- 12794632
TI  - What nuclear cardiology can learn from nuclear oncology.

PMID- 12794633
TI  - Is a revision of the "nuclear cardiology warranty" in order?

PMID- 12794634
TI  - Imaging in the emergency department.

PMID- 12794635
TI  - Favorable cardiac remodeling in dilated cardiomyopathy: potential assessment with
      serial myocardial perfusion imaging.

PMID- 12794636
TI  - Structural and functional insights into PINCH LIM4 domain-mediated integrin
      signaling.
AB  - PINCH is an adaptor protein found in focal adhesions, large cellular complexes
      that link extracellular matrix to the actin cytoskeleton. PINCH, which contains
      an array of five LIM domains, has been implicated as a platform for multiple
      protein-protein interactions that mediate integrin signaling within focal
      adhesions. We had previously characterized the LIM1 domain of PINCH, which
      functions in focal adhesions by binding specifically to integrin-linked kinase.
      Using NMR spectroscopy, we show here that the PINCH LIM4 domain, while
      maintaining the conserved LIM scaffold, recognizes the third SH3 domain of
      another adaptor protein, Nck2 (also called Nckbeta or Grb4), in a manner distinct
      from that of the LIM1 domain. Point mutation of LIM residues in the SH3-binding
      interface disrupted LIM-SH3 interaction and substantially impaired localization
      of PINCH to focal adhesions. These data provide novel structural insight into LIM
      domain-mediated protein-protein recognition and demonstrate that the PINCH-Nck2
      interaction is an important component of the focal adhesion assembly during
      integrin signaling.

PMID- 12794637
TI  - The crystal structure of the proprotein processing proteinase furin explains its
      stringent specificity.
AB  - In eukaryotes, many essential secreted proteins and peptide hormones are excised
      from larger precursors by members of a class of calcium-dependent
      endoproteinases, the prohormone-proprotein convertases (PCs). Furin, the best
      characterized member of the mammalian PC family, has essential functions in
      embryogenesis and homeostasis but is also implicated in various pathologies such
      as tumor metastasis, neurodegeneration and various bacterial and viral diseases
      caused by such pathogens as anthrax and pathogenic Ebola virus strains. Furin
      cleaves protein precursors with narrow specificity following basic Arg-Xaa
      Lys/Arg-Arg-like motifs. The 2.6 A crystal structure of the decanoyl-Arg-Val-Lys
      Arg-chloromethylketone (dec-RVKR-cmk)-inhibited mouse furin ectodomain, the first
      PC structure, reveals an eight-stranded jelly-roll P domain associated with the
      catalytic domain. Contoured surface loops shape the active site by cleft, thus
      explaining furin's stringent requirement for arginine at P1 and P4, and lysine at
      P2 sites by highly charge-complementary pockets. The structure also explains
      furin's preference for basic residues at P3, P5 and P6 sites. This structure will
      aid in the rational design of antiviral and antibacterial drugs.

PMID- 12794638
TI  - Systematic discovery of analogous enzymes in thiamin biosynthesis.
AB  - In all genome-sequencing projects completed to date, a considerable number of
      'gaps' have been found in the biochemical pathways of the respective species. In
      many instances, missing enzymes are displaced by analogs, functionally equivalent
      proteins that have evolved independently and lack sequence and structural
      similarity. Here we fill such gaps by analyzing anticorrelating occurrences of
      genes across species. Our approach, applied to the thiamin biosynthesis pathway
      comprising approximately 15 catalytic steps, predicts seven instances in which
      known enzymes have been displaced by analogous proteins. So far we have verified
      four predictions by genetic complementation, including three proteins for which
      there was no previous experimental evidence of a role in the thiamin biosynthesis
      pathway. For one hypothetical protein, biochemical characterization confirmed the
      predicted thiamin phosphate synthase (ThiE) activity. The results demonstrate the
      ability of our computational approach to predict specific functions without
      taking into account sequence similarity.

PMID- 12794639
TI  - A conditionally replicating adenovirus targeted to tumor cells through activated
      RAS/P-MAPK-selective mRNA stabilization.
AB  - The expression of various proteins associated with rapid responses to
      inflammation and/or proliferation can be controlled at the level of mRNA
      stability. Because tumor cells continually recapitulate intracellular programs of
      proliferation, we have used tumor cell-selective stabilization of mRNA as a means
      to control therapeutic gene expression. We describe an adenoviral vector that is
      conditionally replication competent in which expression of the essential
      adenoviral early region 1A (E1A) gene is regulated by ligation to the 3'
      untranslated region (UTR) of PTGS2 (also known as COX2), the gene encoding
      prostaglandin-endoperoxide synthase 2, allowing activated RAS/P-MAPK-specific
      stabilization of its mRNA. Induction of activated RAS supports replication,
      whereas matched cells in which activated RAS/P-MAPK is not expressed are very
      poor substrates for viral replication both in vitro and in vivo. Further tumor
      targeting strategies will also be required to prevent viral replication at
      extratumoral sites where PTGS2 is normally induced. Many different genes contain
      3' UTRs that control selective mRNA stability under different physiological,
      pathological and tumor-associated conditions. Therefore, generating tumor
      selectivity at the level of mRNA stability is a strategy with broad potential
      applicability in vector design.

PMID- 12794640
TI  - A model of molecular interactions on short oligonucleotide microarrays.
AB  - High-density short oligonucleotide microarrays have become a widely used tool for
      measuring gene expression on a large scale. However, details of the mechanism of
      binding on microarrays remain unclear. Short oligonucleotide probes currently
      synthesized on microarrays are often ineffective as a result of limited sequence
      specificity or low sensitivity. Here, we describe a model of binding interactions
      on microarrays that reveals how probe signals depend on probe sequences and why
      certain probes are ineffective. The model indicates that the amount of
      nonspecific binding can be estimated from a simple rule. Using this model, we
      have developed an improved measure of gene expression for use in data analysis.

PMID- 12794642
TI  - [Suicidal ideation in schizophrenia: relationship with positive and negative
      symptoms, depression and insight].
AB  - OBJECTIVE: To estimate suicidal ideation among schizophrenic patients and compare
      sociodemographic and clinical properties. METHOD: Sixty patients schizophrenic
      according to DSM-IV criteria were included in the study. Half the patients were
      in the acute phase and were inpatients, while the other half were in the stable
      phase and were outpatients. A semistructured sociodemographic form, the Positive
      and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia
      (CDSS) and Schedule for Assessing the Three Components of Insight were used.
      RESULTS: Suicidal ideations were found in 12 (20%) patients. The proportion
      having relationship problems, having attempted suicide in the past, and in the
      acute phase was higher in the group with suicidal ideations than in the group
      without suicidal ideations. The mean number of suicide attempts was also higher
      in the group with suicide ideations. The depression score measured by CDSS was
      higher in the group with suicidal ideations, while there were no relationships
      between the scores of positive and negative symptoms, and the degree of insight
      and suicidal thoughts. CONCLUSION: The high rate of suicidal ideation in our
      sample suggests that, when planning treatment and follow-up for these patients,
      the risk of suicide has to be determined and protective measures have to be
      taken. It suggests that determining depression routinely with scales that can be
      used easily, like CDSS, can be useful for these patients.

PMID- 12794643
TI  - [The psychometric properties of MMPI-2 addiction related supplementary scales on
      alcoholic patients].
AB  - OBJECTIVE: The aim of the study was to investigate criterion-related validity,
      internal-consistency and diagnostic efficiency statistics of the three MMPI-2
      addiction related supplementary scales i.e., MacAndrew Alcoholism Scale (MAC-R),
      Addiction Potential Scale (APS) and Addiction Acknowledgment Scale (AAS). METHOD:
      Sixty-nine male chronic alcoholic patients and 51 male healthy control subjects
      were recruited for the study. All patients satisfied the diagnostic criteria of
      ICD-10 for alcohol dependence. Alcohol and drug modules of Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) were administered to each patient in order
      to give the diagnosis of alcohol dependency. The lifetime severity of drinking
      problems was assessed by the Michigan Alcoholism Screening Test (MAST). RESULTS:
      The comparison of the MMPI-2 results of the study groups revealed that chronic
      alcoholic patients had higher scores on MAC-R, APS and AAS. The investigation of
      the diagnostic efficiency statistics showed that MAC-R and AAS had satisfactory
      sensitivity and specificity for alcoholic patients. As a measure of internal
      consistency, Kuder-Richardson coefficients were found to be satisfactorily high
      for each scale. CONCLUSION: The results of this study indicates that MMPI-2 based
      MAC-R and AAS scales are effective at differentiating between chronic alcoholic
      and control subjects. However, low specificity values of APS seemed to be
      damaging its diagnostic efficiency. Uniformly high Kuder-Richardson coefficients
      suggest that the items that comprise the MAC-R, APS and AAS are satisfactorily
      homogenous.

PMID- 12794644
TI  - [Reliability and validity of the standardized Mini Mental State Examination in
      the diagnosis of mild dementia in Turkish population].
AB  - OBJECTIVE: Reliability and validity of the Mini Mental State Examination in
      differentiating mild dementia from normal controls in Turkish population. METHOD:
      The Standardized Mini Mental State Examination (SMMSE) and its instruction were
      translated into Turkish. A total of 212 subjects with mean age of 77 +/- 6, were
      recruited for the study. 71 were diagnosed to be demented and 141 were evaluated
      as normal controls. The scale total score was analysed for discriminant validity
      using Student's t-test. Sensitivity, specificity, positive and negative
      predictive values and kappa score were calculated for all of the scores between
      18 and 29. Kappa value was calculated for the comparison of the dementia
      diagnosis between the two investigators using the best cut off score obtained in
      the analysis above. RESULTS: Statistical analysis revealed that the Turkish
      version of the SMMSE has high discriminant validity and interrater reliability in
      the diagnosis of mild dementia. The cut off score 23/24 was found to have the
      highest sensitivity (0.91), specificity (0.95), positive and negative predictive
      values (0.90 and 0.95) and kappa score (0.86). Interrater reliability analysis
      showed high correlation (r:0.99) and kappa value (0.92). CONCLUSION: The results
      of this study showed that the Turkish version of the SMMSE has high reliability
      and validity for the diagnosis of mild dementia in Turkish population.

PMID- 12794645
TI  - [The relationship between psychogenic excoriation and psychiatric disorders: a
      comparative study].
AB  - OBJECTIVE: Psychogenic excoriation (PE), characterized by excessive scratching or
      picking of the skin, is not yet recognized as a symptom of a distinct DSM-IV
      disorder. It is a chronic disorder with a high rate of psychiatric comorbidity.
      The purpose of this study was to compare patients diagnosed with PE and another
      group of psychodermatosis patients in terms of comorbid psychiatric disorders.
      METHOD: Thirty-one consecutive subjects were recruited from an outpatient
      dermatology clinic. The control group was composed of 31 patients with a
      dermatological disease other than PE. Subjects were interviewed using the
      Structured Clinical Interview for DSM-III-R, Beck Depression Inventory (BDI),
      Hamilton Anxiety Rating Scale (HARS) and the Yale-Brown Obsession and Compulsion
      Scale (YBOCS). Subjects also completed a semi-structured questionnaire for socio
      demographic data and clinical features. RESULTS: Current major depressive
      syndrome was the most common psychiatric disorder in the PE group. There was a
      statistically significant difference between the two groups in terms of current
      major depressive syndrome (PE group 58.1%, control group 6.5%, p<0.01). Some
      45.2% of the PE group was diagnosed with obsessive compulsive disorder (OCD)
      while the proportion was only 3.7% in the control group. This difference was also
      statistically significant (p<0.01). The PE group scored significantly higher in
      the BDI, HARS and the YBOCS. CONCLUSION: The results of this study point to a
      close relationship between PE and depression and OCD.

PMID- 12794646
TI  - [Depressive symptomatology among elderly residential home residents in Manisa:
      prevalence and related risk factors].
AB  - OBJECTIVE: To determine the prevalence of depression and related factors among
      elderly residential home residents in Manisa. METHODS: The study was carried out
      in all residential homes in Manisa and the surrounding towns. One hundred and
      forty-five residents completed a form asking questions about demographic
      features, health conditions and the pattern of relationships with their
      relatives, the employees of the home, and the other residents. The Geriatric
      Depression Scale Turkish Form (GDS-TF) was used. The data was analysed by
      logistic regression to determine the factors which had an effect on the presence
      of depression. RESULTS: The mean age of the sample was 73.9 +/- 9.2 and the mean
      score of GDS-TF was 11.9 +/- 6.52. Some 35.9% of subjects were depressed
      according to the cutoff point of 13/14 for the GDS-Turkish Form. Associations
      between dissatisfaction with the perceived social level (p=0.004), decline in the
      ability to perform personal care (p=0.045), having worries about leaving the home
      (p<0.001), the lack of enthusiasm for participating in social activities
      (p=0.007), not being pleased with the physical conditions of the home (p=0.032)
      and the presence of depression were determined. CONCLUSION: The prevalence of
      depression, which is common in residential homes is not associated with the
      social support from outside the home, and the feelings of belonging towards the
      institution and other residents are more important than non-institutional social
      support.

PMID- 12794647
TI  - [Genetic epidemiology: its use in psychiatric research].
AB  - Psychiatric disorders, a growing health concern, are believed to occur due to the
      interaction of multiple factors. Identification of the causes of psychiatric
      disorders and related risk factors will increase the efficiency of the
      development and implementation of relevant preventive measures. Genetic
      epidemiology studies the frequency, distribution and causes of diseases and
      enables one to investigate how genetic and/or environmental factors interact in
      producing the complex phenotypes of various disorders. Genetic research is often
      initiated when a clinician detects similar cases of psychiatric disorders among
      relatives of patients admitted to the clinic and/or when the frequency of a
      particular disease is found to be significantly higher than expected in a
      particular group of the population or place or at a particular time. High
      occurrence rates of a particular psychiatric disease could reflect a genetically
      transmitted disorder, could be due to familial aggregation of disease risk
      factors, or could be linked to another genetically transmitted disease. Preceding
      comprehensive genetic research, the role of chance, bias, and confounding factors
      should definitely be excluded. This review summarizes the epidemiologic study
      designs used to investigate the role of genetic structure in the occurrence of
      psychiatric disorders, the issues to be considered in designing and conducting
      such studies and potential sources of error.

PMID- 12794648
TI  - [Domestic violence and its developmental dimension: a different perspective].
AB  - Domestic violence is a problem which severely threatens physical and mental
      health in Turkey as well as the rest of the world. In spite of this, there is
      almost no discussion of the problem in psychoanalytic journals. Although
      aggression is discussed thoroughly in the psychoanalytic literature, the number
      of articles on violence is very limited. The number of articles on domestic
      violence is even more limited. In this article, domestic violence is examined
      from a psychoanalytic point of view, focusing especially on developmental
      aspects. The mutual impacts of developmental processes and domestic violence on
      each other are discussed. Developmental issues which make women more vulnerable
      to trauma, transmission of domestic violence from generation to generation,
      transgenerational cycle of aggression, gender differences in expressing
      aggression, other developmental issues which play a possible role in domestic
      violence, children who "witness" domestic violence, and adult victims of domestic
      violence are among the topics discussed. The author has tried to elaborate her
      viewpoint by adapting some psychoanalytic ideas to the problem of domestic
      violence, explaining and discussing the existing limited number of ideas directly
      on domestic violence in the psychoanalytic literature, and adding her own
      perspective on the developmental dimension of the issue.

PMID- 12794649
TI  - [Ecchymosis associated with the use of fluoxetine: case report].
AB  - Selective Serotonin Reuptake Inhibitors (SSRI) are well established in
      psychopharmacological therapy. SSRIs have been shown to be very effective in the
      treatment of depressive, anxiety and obsessive-compulsive disorders and have a
      favorable side effect profile. Although bleeding events are rare, there may be
      potentially severe hematologic complications following treatment with SSRIs.
      Fluoxetine has been reported to cause ecchymosis, bleeding and other hematologic
      problems. The aim of this article is to report a case of suspected fluoxetine
      induced ecchymosis and to review the literature about this adverse effect. CASE
      SUMMARY: A 23-year-old woman was diagnosed with depressive disorder according to
      DSM-IV criteria and treated with fluoxetine 20 mg/day. After treatment for 10
      weeks, the patient reported ecchymosis without any trauma. Her complete blood
      cell count, prothrombin time, partial thromboplastin time, bleeding time and
      other hematologic screening tests were within the normal limits. Her complete
      physical examination was also normal. After the medication was discontinued for 4
      weeks, ecchymosis disappeared. A month later, the patient took fluoxetine for a
      week, and then the ecchymosis restarted. Fluoxetine was suspected to be the cause
      of these lesions. SSRIs cause these side effects by disrupting the normal
      platelet aggregation process through the blockade of serotonin uptake into
      platelets. For this reason, caution is recommended when using fluoxetine and
      other SSRIs in patients with thrombocytopenia or suspected platelet dysfunction.

PMID- 12794651
TI  - [Distinguishing depressive from nondepressive patients in schizophrenia in terms
      of symptomatology].
AB  - OBJECTIVE: Schizophrenia is a syndrome with five dimensions and it contains
      positive symptoms, negative symptoms, disorganization, depression, and cognitive
      symptoms. Depression which is one of these dimensions can be seen with every
      dimension and in every phase of schizophrenia. In this study our aim was to
      examine the overlapping features and the discriminating symptoms of depression
      comorbid with schizophrenia. METHOD: The subjects consisted of 30 patients
      diagnosed as schizophrenic with a concurrent depression, disorder, and 30
      patients diagnosed as schizophrenic without a concurrent depression, admitted to
      the outpatient department of two university hospitals. Patients were assessed
      using the following measures: Calgary Depression Scale for Schizophrenia (CDSS),
      Scales for Assessment of Positive and Negative Symptoms (SAPS and SANS
      respectively), and Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: For
      determining the overlapping features of schizophrenia with depression, symptoms
      drawn from SAPS, SANS and ESRS were correlated with CDSS score, and affective
      flattening, apathy, attention, and delusions were significantly correlated with
      total score of CDSS. By Wilks' Lambda method, the discriminating symptoms of the
      depressive and schizophrenic patients from the only schizophrenic patients were
      found to be depressive mood and feelings of worthlessness. CONCLUSION: The shared
      nature of the overlapping features and discriminating symptoms is the emotional
      component affecting the presence of depression comorbid with schizophrenia.
      Negative affectivity is the dominance of negative-loaded feelings in the
      emotional component. In symptomatology, the presence of negative affectivity in
      the emotional component is suggested to be a specifier for depression in
      schizophrenia.

PMID- 12794652
TI  - [Is there any correlation between self-perception and psychopathology in
      adolescence?].
AB  - OBJECTIVE: In this study, the relation between self-perception and
      psychopathology is examined trying to answer the question of whether the self
      perception profiles of the adolescents who have admitted to an outpatient unit of
      a psychiatry clinic are different from those of the adolescents who have not.
      METHOD: The study is a cross-sectional controlled study. There are two groups one
      of which is the group of adolescents who have admitted to the outpatient
      adolescent clinic of the Social Security Hospital of Ankara and the other is the
      control group. Self-Perception Profile for Adolescents (SPPA) and SCL-90-R were
      administered to the groups. DSM-IV diagnoses were made by two clinicians via
      interviews with adolescents. The differences in the domains of SPPA between two
      groups were assessed via multivariate and then univariate analysis. RESULTS AND
      CONCLUSION: In the domains of SPPA, the global self-worth and the behavior in the
      relationships, the adolescent group who has admitted to the psychiatry clinic was
      found to be significantly lower than that of the adolescent group who has not.

PMID- 12794653
TI  - [Tourette disorder in children and adolescents: sociodemographic, clinical
      features and comorbidity].
AB  - OBJECTIVE: The aim of this study was to evaluate the sociodemographic and
      clinical features of children and adolescents with Tourette Disorder (TD)
      according to DSM-IV who are applied to our outpatient clinic and to determine
      clinical significance of relationship between the sociodemographic features and
      the severity of vocal, motor tics, and also to determine frequency of comorbid
      conditions and diagnosis according to DSM-IV. METHOD: Twenty eight children and
      adolescents (23 boys, 5 girls) were included in this study. Sociodemographic
      features of cases were recorded and Beck Children Depression Inventory (CDI),
      Maudsley Obsessive Compulsive Questionnaire (MOCQ), Goetz Tics Evaluation Scale
      were administered to all children. Clinical features of TD and the comorbid
      diagnosis were assessed in detail through psychiatric interview according to DSM
      IV. RESULTS: The mean age of the cases at the time of referral was 124 +/- 32
      months. Twenty one of the cases (75%) had obsessive compulsive disorder, 4 of
      them (14.2%) had attention deficit hyperactivity disorder (ADHD), 4 of them
      (14.2%) had major depression as a comorbid disorder. The most common motor tic
      was eye blinking and vocal tic was throat cleaning. Coprolali was present in
      32.1% of the cases was found to appear in older children. Besides, no significant
      causal relationship between prenatal, natal, and postnatal conditions of the
      cases and TD. CONCLUSIONS: The results of the study suggest that there are
      several common pathologies in the etiology of TD, OCD, ADHD because of the high
      comorbidity present between these disorders.

PMID- 12794654
TI  - [Body dysmorphic disorder in psychiatric outpatients: diagnosis, other
      psychiatric diagnosis, demographic and clinical correlates].
AB  - OBJECTIVE: We assessed the clinical and demographic properties and comorbidity of
      47 patients with body dysmorphic disorder (BDD). METHOD: Fifty-four patients with
      BDD among 4768 consecutive outpatients over a 5-year period were reviewed and
      invited for comprehensive re-examination. A total 47 patients (male female=26:21)
      were rediagnosed according to DSM-IV criteria for BDD and comorbid lifetime
      psychiatric disorders using SCID-I. RESULTS: The mean age of BDD patients was
      23.1 +/- 5.5 years and the mean age at onset of BDD was 17.6 +/- 2.4 years. The
      face (27.7%) and nose (25.5%) were the most common areas of concern, followed by
      hair loss/thinning, legs/knees, hands, and thinness. Obsessive-compulsive
      disorder (31.9%), major depression (21.3%), and social phobia (17.0%) were the
      most frequent additional lifetime DSM-IV diagnoses. Eleven patients (23.4%) had
      ideas of reference and 9 patients (19.1%) had delusions of deformity or
      reference. Four patients (8.5%) had made suicide attempts. CONCLUSION: BDD may be
      related to obsessive-compulsive disorder in several aspects, including patterns
      of comorbidity and symptom profile. These findings also support the idea that BDD
      has a psychotic subtype that is closely related to the primary disorder. BDD
      patients among the Turkish population have a symptom profile similar to those in
      western countries except for lower suicide attempts.

PMID- 12794655
TI  - [The public attitudes towards schizophrenia in a rural area in Turkey].
AB  - OBJECTIVE: To determine the public's attitude about schizophrenia and its related
      factors in a rural population. METHODS: This study was carried out in a village
      of Manisa. Of the 245 subjects which met the inclusion criteria, 230 subjects
      were reached and 208 of them constituted the sample of this study. The subjects
      filled out the sociodemographic information form and the 32-item subscale for
      schizophrenia of a public survey form which was developed by Psychiatric Research
      and Education Center. RESULTS: Of the 208 subjects, 76.3% appraised the
      schizophrenia as an illness, 62.0% considered it as a mental disease, 76.9% noted
      that social problems were the most frequent etiological factor, 66.8% denoted
      that the patient should consult with a psychiatrist for the treatment, 61.5%
      indicated that they would feel uncomfortable with a neighbor with schizophrenia,
      61.1% declared that they didn't want to work with anyone with schizophrenia.
      CONCLUSION: The majority of subjects in rural population recognize the
      schizophrenia as a mental disease. Social problems are determined as the first
      rank etiological factor by the subjects. The public has an adequate knowledge
      about the treatment of schizophrenia. However they hesitate to apply to
      psychiatric treatment because of the fear of stigmatisation. The public has a
      reluctant attitude in becoming close to the patients and has a rejective attitude
      in keeping a certain distance with the patients. The sociodemographic factors do
      not seem to have any influence on the attitudes towards the schizophrenia.

PMID- 12794656
TI  - [The psychopathology of immigrants and refugees].
AB  - The twentieth century witnessed major waves of emigration, exile and taking
      refuge abroad. In this paper, a review of the psychiatric literature published
      between 1990 and 2000 in English and Turkish is presented. Although refugees are
      considered to differ from economic migrants in a number of respects, they both
      experience culture and language change and may experience family disruption,
      social isolation, and hostility from the population of the host country.
      Accordingly, all refugees and immigrants go through stages of resettlement and
      need to integrate their past cultural experiences into their new life and
      culture. The process of integration depends on the subjects' age, mental
      integrity, and on the conditions he/she lives in. Research indicates that
      children acculturate more quickly and learn language faster than elders; but they
      may suffer from role reversal when they are expected to be linguistic and
      cultural translators for their parents. Young adults at the stage of identity
      formation can be cut off and feel alienated. Elderly persons have a higher risk
      of culture shock as they leave behind more memories and connections. These
      trigger different types of anxieties. The literature shows high levels of
      acculturative distress, and psychiatric disorders such as post-traumatic stress
      disorder, anxiety and depression, and refugees are considered to be at risk for
      suicidal behavior. The complex social and psychological needs of refugee and
      immigrant families place demands on special services for children, adolescents
      and adults.

PMID- 12794657
TI  - [Medically unexplained symptoms].
AB  - Patients with physical symptoms for which no medical explanation can be found are
      relatively common in general practice. Patients with medically unexplained
      symptoms are frequently frustrating to physicians both in primary and secondary
      care and utilize health sources disproportionately. They frequently attend both
      primary care units and hospitals and are usually not satisfied with the care they
      receive. Medically unexplained symptoms in patient populations are strongly
      associated with psychiatric pathology and with anxiety and depression in
      particular. They are also linked to personality pathology, childhood adversity,
      adult trauma or medically unexplained symptoms in childhood. The predictive value
      of alexithymia in determining these symptoms is controversial. Patients who have
      high negative affectivity or neuroticism tend to score high on measures of
      physical symptoms. These symptoms have a high degree of co-occurrence. The same
      person may meet the diagnostic criteria for several functional somatic syndromes
      simultaneously. The clinician should be aware of the cultural and social shaping
      of the bodily experience of these patients and hence acknowledge the somatic
      nature and reality of the symptoms. The clinician should make the person feel
      understood and establish a positive collaborative relationship. This would enable
      him/her to correct misconceptions about the disease and give a positive
      explanation of symptoms. Antidepressant therapy and cognitive-behavioural
      psychotherapy have been proved to be moderately effective in this group of
      patients. Because of the high disability that might be caused by these symptoms,
      psychiatrists and primary and secondary care physicians should pay careful
      attention to this clinical condition. These symptoms may also aid us in
      challenging the long-held idea of mind-body dualism which is inherent in Western
      biomedicine.

PMID- 12794658
TI  - [Burning mouth syndrome and depression: a case report].
AB  - We present a 63-year-old male patient with major depression, characterised by
      prominent somatic symptoms localised especially around the mouth, whose
      complaints started just after a prostate operation. The symptoms consisting of
      burning in the mouth, pain, dry mouth (xerostomia), an unpleasant and strange
      feeling of taste and itching, are all consistent with burning mouth syndrome.
      Burning mouth syndrome is a common disorder, usually affecting elderly females,
      characterised by intractable pain and burning in the oral cavity, evident
      especially in the tongue, together with a normal mouth mucosa. In the scientific
      literature a variety of terms are used to describe similar symptoms, such as
      glossodynia, glossopyrosis, stomatodynia and oral dysestesia. Most patients
      suffer from the syndrome for a long time, ranging from months up to years. The
      onset was reported to be gradual for most of the subjects, although many patients
      relate the onset of symptoms to previous dental procedures or to a previous
      medical illness. Burning mouth syndrome has a multifactorial etiology. Anxiety
      disorder, hypochondriasis, conversion disorder and especially depression may be
      considered amongst the psychological factors responsible for this situation. The
      psychological findings in burning mouth syndrome patients may be either the
      consequence of the chronic pain condition or its cause. It is well known that
      those patients had a relatively high percentage of psychiatric or psychological
      treatment in the past and/or present. After excluding organic factors, depression
      should be considered in old patients with predominant mouth complaints.

PMID- 12794659
TI  - [Is substance abuse among physicians a problem?].
AB  - In today's medical community, there is growing concern about substance use among
      physicians, not only because of their own health, but also because of the
      potential adverse effects on their clinical practices. Physicians affect public
      health both by treatment and preventive studies and as role models. Prevalence
      data concerning substance abuse are generally lacking. There is no consensus on
      the rates of substance abuse being higher among physicians than among the general
      public. Physicians are less likely to smoke cigarettes and use illicit substances
      (like marijuana, cocaine and heroin) and more likely to use alcohol and two types
      of prescription medications--benzodiazepines and minor opioids--compared with
      their age groups. Doctors are at special risk of developing addiction problems
      owing to the strain of medical practice, erosion of the taboo against injecting
      and using opiates, and particularly access to supplies. The most common
      precipitating factors mentioned are physical pain and illness, usually chronic,
      with family tragedy such as death of a wife or child next. The third most common
      factor is an addicted wife. Stress, overwork and marital problems are also
      mentioned. No data were found about physicians' substance use in Turkey. This
      article generally aims to review the knowledge on the prevalence of substance use
      among physicians, the drug of choice, the development of dependence, the
      treatment and prognosis and to discuss the importance of this issue by evaluating
      three cases treated at the Alcohol and Drug Addiction Treatment and Research
      Center (AMATEM), Bakirkoy State Hospital for Mental and Neurological Diseases.

PMID- 12794661
TI  - [Evaluation of regional cerebral blood flow changes in panic disorder with Tc99m
      HMPAO SPECT].
AB  - OBJECTIVE: To evaluate the differences in regional cerebral blood flow (rCBF) and
      rCBF asymmetry index values of panic disorder patients and a control group, using
      Tc99m-HMPAO SPECT. In addition, the influence of comorbid agoraphobia on the rCBF
      and rCBF asymmetry index values of the panic disorder patients was also
      investigated. METHOD: The rCBF and rCBF asymmetry index values of 22 panic
      disorder patients, 9 with agoraphobia and 13 without agoraphobia, and 19 healthy
      controls were obtained using SPECT. Both (1) the panic disorder and control
      groups and (2) panic disorder groups with and without agoraphobia were compared
      in terms of the measured values. RESULTS: A decrease in blood perfusion in the
      bilateral frontal region, a relative increase in blood perfusion in the right
      medial frontal and right superior frontal regions and a relative blood flow
      increase in the right medial frontal region according to rCBF asymmetry index
      values were determined in panic disorder patients. In the patients with
      agoraphobia, the decrease in blood perfusion in the right occipital region, and
      the relative increase in the right superior temporal region according to rCBF
      asymmetry index values were significantly higher than those in subjects without
      agoraphobia. CONCLUSION: The decrease in the rCBF in the bilateral inferior
      frontal regions in panic patients may be related to the amygdala activation
      decreasing cerebral blood flow in the frontal region and/or the hyperactivation
      of the locus ceruleus. The explanations of the etiology of panic disorder are
      valid only if they are supported with clinical evidence from future studies.

PMID- 12794662
TI  - [Reliability and validity of a handedness questionnaire].
AB  - OBJECTIVE: In this study, the validity and reliability of the hand preference
      item of a 13-item questionnaire adapted from Chapman and Chapman (1987) were
      investigated. METHOD: This questionnaire requires subjects to indicate which hand
      they usually use for various actions as follows: writing, drawing, throwing,
      using a hammer, using a toothbrush, using an eraser on paper, using scissors,
      holding a match when striking it, stirring a can of paint, using a spoon, using a
      screwdriver, twisting off the lid of a jar, and using a knife. Each item was
      scored as "1" for right, "2" for either, or "3" for left, and the handedness of
      subjects was scored from 13 (the strongest right-hand preference) to 39 (the
      strongest left-hand preference). In this study, 449 subjects filled in the
      questionnaire, and 43 subjects attended the test-retest study 3 weeks after the
      first examination. In order to determine the validity of the questionnaire, fine
      motor performance was measured using a finger tapping task, and the eye and foot
      preferences of the subjects were evaluated. RESULTS: The test-retest reliability
      (r=.993) and internal consistency (Cronbach's Alpha=.97) were found to be high.
      In item-total score analysis, the best single item was "using a hammer", while
      the worst item was "twisting off the lid of a jar". Factor analysis yielded two
      factors, skilled and unskilled activities. Handedness scores were found to show a
      significant correlation with foot preference scores and the dominance score of
      the finger tapping task. CONCLUSION: The results suggest that the handedness
      questionnaire is reliable and valid in measuring handedness.

PMID- 12794663
TI  - [Reliability and validity of Turkish translation of Young Mania Rating Scale].
AB  - OBJECTIVE: The reliability and validity of the Turkish translation of the Young
      Mania Rating Scale (YMRS) were determined in this study, since it is the most
      common scale used in clinical studies of mood disorders. METHOD: Fifteen male and
      15 female inpatients who were diagnosed as having "Bipolar Mood Disorder--Recent
      Episode Mania", were given YMRS by two experienced psychiatrists, while another
      experienced psychiatrist gave the Bech-Rafaelsen Mania Scale (BRMS)
      simultaneously to the same patient population hospitalized in Bakirkoy State
      Hospital for Psychiatric and Neurological Diseases, Psychiatry and Mood Disorders
      Inpatient Unit 5. The internal consistency of the Turkish version of YMRS was
      evaluated by the Cronbach's Alpha test, while item/item, item/total, and cross
      validity correlations were evaluated by the Pearson correlation test. Inter-rater
      agreement and consistency was evaluated by weighted kappa analysis. RESULTS: The
      internal consistency coefficient (Cronbach's alpha) was 0.79 for both
      researchers. Correlations of the items individually with the YMRS total scores
      were between 0.407 and 0.847. Agreement of the interviewers for the items was
      between 63.3%-95% and kappa values for the items were between 0.114 and 0.849.
      Correlation coefficients of YMRS and BRMS of the researchers were 0.72 for the
      first researcher and 0.71 for the second researcher. CONCLUSION: The Turkish
      translation of YMRS was found to be valid and reliable.

PMID- 12794664
TI  - [Evaluation of mental health services in primary health care settings in the city
      centre of Eskisehir].
AB  - OBJECTIVE: The purpose of this study was to determine the proportion of cases
      thought to have a mental disorder, and/or proposed treatment. Additionally, we
      assessed the relationship between age and sex regarding mental disorders, and the
      treatments recommended to patients diagnosed as mentally ill by their physicians.
      METHOD: During a one year period the out-patient polyclinic registration lists of
      313,139 patients attending primary health care clinics in the centre of Eskisehir
      were scanned by the researchers. RESULTS: The proportion of mental disorders in
      patients attending primary care centres at least once owing to a mental disorder
      was 2.34%. However, this proportion in patients attending once was 1.04%.
      Compared with men, women attended primary care clinics more frequently. The most
      common diagnoses were depression and anxiety disorders; these were more frequent
      in women than in men. The most frequently prescribed medicines for mental
      disorders were anxiolytics and antidepressants. CONCLUSION: The low levels of
      diagnoses and treatments of psychiatric disorders in primary care settings are
      thought to be associated with the following: physicians under-recognising mental
      disorders despite being educated about this subject, mental screening scales not
      being used, patients being unaware of their diseases and giving insufficient
      information to physicians about mental symptoms, co-occurrence of medical
      diseases and psychiatric problems, the physicians' negative approach to patients,
      and the physicians' tendency not to give importance to drug or medical records.

PMID- 12794665
TI  - [The validity, reliability and factor structure of the Brief Symptom Inventory
      (BSI)].
AB  - PURPOSE: The Brief Symptom Inventory is an instrument used in psychopathological
      evaluations. The standardization study of the instrument was carried out
      previously in a sample of university students (mean age=21.02) by the authors
      (Sahin & Durak, 1994). The purpose of the current study was to investigate
      whether the psychometric characteristics obtained for that sample were also valid
      for adolescents. METHOD: The sample consisted of a total of 559 adolescents (287
      female and 272 male), randomly chosen from different socio-economic backgrounds,
      living in different neighbourhoods in Ankara. The other instruments used for
      validation were the Social Comparison Scale, the Beck Depression Inventory, the
      Trait Anxiety Scale, and the Life Satisfaction Scale. RESULT: The factor analyses
      revealed five factors whose item distribution matched very closely that of the
      previous study on university students. The alpha coefficients of the factor
      subscale ranged between .70 (for depression) and .88 (for somatization). The
      correlation coefficients of the factor subscale with the other instruments ranged
      between -.45 (p<.001) and .71 (p<.001). The current study also contains the
      results of the analyses in terms of the demographic variables and the three index
      scores that can be obtained from the inventory. DISCUSSION: The findings
      concerning the factorial structure and concurrent validity of the BSI with the
      criterion measures show that the instrument can be used with adolescents as well.
      The factorial structure obtained with the current adolescent sample is very
      similar to the one obtained with the university sample (Sahin & Durak, 1994). The
      researchers think that the same factor subscale can be used with adolescent
      samples as well.

PMID- 12794666
TI  - [Acute rheumatic fever, Sydenham's chorea and psychopathology].
AB  - Acute rheumatic fever (ARF) is an autoimmune disorder that is triggered by group
      A beta-hemolytic streptococcal infections. ARF consists of several combinations
      of carditis, polyarthritis and Sydenham's chorea, and rarely seen erythema
      marginatum and subcutaneous nodules. Sydenham's chorea is seen in about 20% of
      patients with ARF. As a late symptom of ARF, Sydenham's chorea usually occurs 3
      months or longer after the streptococcal infection. Sydenham's chorea is a
      neuropsychiatric disorder that may present with emotional lability, anxiety,
      obsessive compulsive symptoms, attention deficit and hyperactivity symptoms or
      tics. Obsessive-compulsive symptoms occur in 70% of patients with Sydenham's
      chorea. The role of the autoimmune mechanisms and the dysfunction of the basal
      ganglia have been demonstrated in Sydenham's chorea. Antibodies against group A
      beta-hemolytic streptococcus cross-react with basal ganglia. Pediatric Autoimmune
      Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
      shares the same mechanism with Sydenham's chorea, but PANDAS has not been shown
      to require penicillin prophylaxis. Thus it is important to distinguish between
      them. Sydenham's chorea is associated with adulthood OCD, Tourette syndrome and
      schizophrenia. These features make Sydenham's chorea an explanatory model for
      obsessive-compulsive disorder (OCD) and related disorders. This poststreptococcal
      disorder provides a treatment opportunity with new therapies like antibiotic
      therapy, plasma exchange and intravenous immunoglobulin therapy for psychiatric
      disorders. In this paper we summarize the phenomenological and treatment studies
      of OCD, attention deficit and hyperactivity disorder (ADHD), and tic disorders in
      subjects with ARF, with or without Sydenham's chorea.

PMID- 12794667
TI  - [Schizophrenia and the family: difficulties, burdens, emotions, needs].
AB  - Treating patients with schizophrenia mostly in the community causes more problems
      for the families. Shame, guilt, fear, helplessness, hopelessness, and anger are
      feelings frequently experienced by families. The main difficulties are financial
      problems, intra-familial conflicts, negative effects on social life, and the
      rejecting attitude of the community towards the patients. Negative symptoms are
      especially burdensome for the families. Families with inadequate social support,
      with high expressed emotion, and who cannot use effective coping styles have
      heavier burdens. When the relationship between schizophrenia and family is
      investigated in a historical context, it is seen that most investigators
      supporting psychological theory consider the family to be the cause of the
      disease. These theories, which depend mostly on clinical observations and which
      have damaged the relationship between the clinicians and the family members, have
      lost their validity during the last thirty years. Family should be included in
      the treatment plan. Hospitalization due to the first psychotic episode or further
      psychotic recurrences is the most convenient period for establishing contact with
      the families. One should approach the family in a supportive and empathic manner,
      without putting any blame on them. If maladaptive coping styles are being used,
      one should help the family to change to adaptive ones. In addition to educative
      and supportive groups, more specific methods like cognitive-behavioral therapies
      can be used. Families should be supported in terms of forming non-governmental
      organizations.

PMID- 12794668
TI  - [Narcissistic personality disorder and factitious disorder on a borderline
      personality organization basis: a psychoanalytic psychotherapy process].
AB  - The aim of this presentation is to summarize the changes occurring during the
      psychoanalytic psychotherapy of a dystonic (due to anoxic injury), 25-years-old
      female patient both from the standpoint of diagnosis and dynamics as well as the
      changes occurring in the therapist. The patient was finally diagnosed as having
      narcissistic disorder with factitious traits on a borderline personality
      organization and was twice hospitalized for a wide variety of symptoms, such as
      suicidal attempts, auditory and visual hallucinations, animistic thoughts,
      obsessive compulsive symptoms, dissociative episodes, and fear of abandonment.
      Hospitalized treatment was started on a weekly basis. Avoidance of
      interpretation, acceptance of her fantasies, outbursts and hostile behaviour
      helped the patient to reveal herself as a helpless and lonesome person trying to
      get attention with pseudo-symptoms created throughout the therapy. The patient
      finally established a trusting relationship with the therapist. This, in turn
      helped the therapist to become more attuned to the patient's difficulties. It is
      obvious that establishing a positive working relationship is the basis of
      psychotherapy and that even on a once a week basis significant changes can occur
      in a patient's attitude towards his/her life and future. Another point emphasized
      in this paper is the importance of supervision, which helped the therapist to
      overcome prejudices and become more flexible.

PMID- 12794669
TI  - Respiratory and reproductive paleophysiology of dinosaurs and early birds.
AB  - In terms of their diversity and longevity, dinosaurs and birds were/are surely
      among the most successful of terrestrial vertebrates. Unfortunately, interpreting
      many aspects of the biology of dinosaurs and the earliest of the birds presents
      formidable challenges because they are known only from fossils. Nevertheless, a
      variety of attributes of these taxa can be inferred by identification of shared
      anatomical structures whose presence is causally linked to specialized functions
      in living reptiles, birds, and mammals. Studies such as these demonstrate that
      although dinosaurs and early birds were likely to have been homeothermic, the
      absence of nasal respiratory turbinates in these animals indicates that they were
      likely to have maintained reptile-like (ectothermic) metabolic rates during
      periods of rest or routine activity. Nevertheless, given the metabolic capacities
      of some extant reptiles during periods of elevated activity, early birds were
      probably capable of powered flight. Similarly, had, for example, theropod
      dinosaurs possessed aerobic metabolic capacities and habits equivalent to those
      of some large, modern tropical latitude lizards (e.g., Varanus), they may well
      have maintained significant home ranges and actively pursued and killed large
      prey. Additionally, this scenario of active, although ectothermic, theropod
      dinosaurs seems reinforced by the likely utilization of crocodilian-like,
      diaphragm breathing in this group. Finally, persistent in vivo burial of their
      nests and apparent lack of egg turning suggests that clutch incubation by
      dinosaurs was more reptile- than birdlike. Contrary to previous suggestions,
      there is little if any reliable evidence that some dinosaur young may have been
      helpless and nestbound (altricial) at hatching.

PMID- 12794670
TI  - The role of energy availability in Mammalian hibernation: a cost-benefit
      approach.
AB  - Hibernation is widely regarded as an adaptation to seasonal energy shortage, but
      the actual influence of energy availability on hibernation patterns is rarely
      considered. Here we review literature on the costs and benefits of torpor
      expression to examine the influence that energy may have on hibernation patterns.
      We first establish that the dichotomy between food- and fat-storing hibernators
      coincides with differences in diet rather than body size and show that small or
      large species pursuing either strategy have considerable potential scope in the
      amount of torpor needed to survive winter. Torpor expression provides substantial
      energy savings, which increase the chance of surviving a period of food shortage
      and emerging with residual energy for early spring reproduction. However, all
      hibernating mammals periodically arouse to normal body temperatures during
      hibernation. The function of these arousals has long been speculated to involve
      recovery from physiological costs accumulated during metabolic depression, and
      recent physiological studies indicate these costs may include oxidative stress,
      reduced immunocompetence, and perhaps neuronal tissue damage. Using an optimality
      approach, we suggest that trade-offs between the benefits of energy conservation
      and the physiological costs of metabolic depression can explain both why
      hibernators periodically arouse from torpor and why they should use available
      energy to minimize the depth and duration of their torpor bouts. On the basis of
      these trade-offs, we derive a series of testable predictions concerning the
      relationship between energy availability and torpor expression. We conclude by
      reviewing the empirical support for these predictions and suggesting new avenues
      for research on the role of energy availability in mammalian hibernation.

PMID- 12794671
TI  - The role of energy availability in Mammalian hibernation: an experimental test in
      free-ranging eastern chipmunks.
AB  - Reduced torpor expression by hibernating mammals is often attributed to
      physiological constraints that limit their hibernation ability but may instead
      reflect adaptive, plastic responses to surplus energy availability. We evaluated
      this hypothesis by supplementing the food hoards of free-ranging eastern
      chipmunks (Tamias striatus) before hibernation and then documenting their use of
      torpor during the subsequent winter. In both years of study, chipmunks that
      received additional food were euthermic more than twice as frequently as
      nonsupplemented individuals. Furthermore, when food-supplemented individuals did
      express torpor, their minimum collar temperature was 5 degrees -10 degrees C
      warmer than nonsupplemented animals. These results indicate that reduced torpor
      expression by hibernators can result from an absence of energetic necessity
      rather than a lack of physiological capability and suggest that even endotherms
      sequestered in a hibernaculum may benefit from maintaining an elevated body
      temperature whenever possible.

PMID- 12794672
TI  - Establishment of the fatty acid profile of the brain of the king penguin
      (Aptenodytes patagonicus) at hatch: effects of a yolk that is naturally rich in n
      3 polyunsaturates.
AB  - Because the yolk lipids of the king penguin (Aptenodytes patagonicus) contain the
      highest concentrations of long-chain n-3 polyunsaturated fatty acids yet reported
      for an avian species, the consequences for the establishment of the brain's fatty
      acid profile in the embryo were investigated. To place the results in context,
      the fatty acid compositions of yolk lipid and brain phospholipid of the king
      penguin were compared with those from three other species of free-living birds.
      The proportions of docosahexaenoic acid (22:6n-3; DHA) in the total lipid of the
      initial yolks for the Canada goose (Branta canadensis), mallard (Anas
      platyrhynchos), moorhen (Gallinula chloropus), and king penguin were (% w/w of
      fatty acids) 1.0+/-0.1, 1.9+/-0.2, 3.3+/-0.1, and 5.9+/-0.2, respectively. The
      respective concentrations of DHA (% w/w of phospholipid fatty acids) in brains of
      the newly hatched chicks of these same species were 18.5+/-0.2, 19.6+/-0.7,
      16.9+/-0.4, and 17.6+/-0.1. Thus, the natural interspecies diversity in yolk
      fatty acid profiles does not necessarily produce major differences in the DHA
      content of the developing brain. Only about 1% of the amount of DHA initially
      present in the yolk was recovered in the brain of the penguin at hatch. There was
      no preferential uptake of DHA from the yolk during development of the king
      penguin.

PMID- 12794673
TI  - Do T3 levels in incubating eiders reflect the cost of incubation among clutch
      sizes?
AB  - Complete development of avian eggs requires external heat, inducing in most
      species an energetic cost of incubation for the parents. Triiodothyronine (T(3))
      has been implicated in the control of the metabolic rate and is decreased during
      fasting in most bird species. This raises the question of the regulation of T(3)
      during reproduction when incubation (thus heat production) is associated with
      fasting (and energy sparing). In this study, plasma concentrations of T(3) were
      studied for different clutch sizes in incubating, as well as in nonincubating,
      fasting female eiders. Our results show that the T(3) levels decrease during
      fasting in nonincubating birds, whereas they were maintained during the
      incubation fast. T(3) levels increased in female eiders at hatching. The plasma
      T(3) level did not vary among natural clutch sizes in eiders but did so when
      manipulated. T(3) levels increased when eggs were added (to a maximum of six
      eggs, i.e., the biggest natural clutch size) or removed (to two eggs, i.e., the
      smallest natural clutch size). Our results suggest that (1) high T(3) levels
      during incubation may participate to a threshold of heat production and
      incubation metabolic rate in eiders despite the fact that they are fasting; (2)
      since T(3) is associated with the energy expenditure in birds, incubating an
      enlarged or reduced clutch size may lead to a higher energetic cost of incubation
      in eiders; and (3) the energy demand of the ducklings at hatching is probably
      important, as the female T(3) concentrations are then at their highest levels.
      Thus, any modification of the natural clutch size leads to a rise in the T(3)
      level of the incubating female, suggesting an additional cost of incubation.
      Knowing that there is no variation of T(3) levels among natural clutch sizes,
      this study suggests that a female eider produces a number of eggs corresponding
      to the energy she can invest in incubation.

PMID- 12794674
TI  - Alkaline environmental pH has no effect on ammonia excretion in the mudskipper
      Periophthalmodon schlosseri but inhibits ammonia excretion in the related species
      Boleophthalmus boddaerti.
AB  - Experiments were performed to evaluate the effects of alkaline environmental pH
      on urea and ammonia excretion rates and on tissue urea, ammonia, and free amino
      acid concentrations in two mudskippers, Periophthalmodon schlosseri and
      Boleophthalmus boddaerti. Periophthalomodon schlosseri is known to be capable of
      actively excreting ammonia. The rate of ammonia excretion in B. boddaerti exposed
      to 50% seawater (brackish water, BW) at pH 9 decreased significantly during the
      first 2 d of exposure when compared with that of specimens exposed to pH 7 or 8.
      This suggested that B. boddaerti was dependent on NH(3) diffusion for ammonia
      excretion, as in most fishes. It was incapable of detoxifying the accumulating
      endogenous ammonia to urea but could store and tolerate high concentrations of
      ammonia in the muscle, liver, and plasma. It did not undergo reductions in
      proteolysis and/or amino acid catabolism in alkaline water, probably because the
      buildup of endogenous ammonia was essential for the recovery of the normal rate
      of ammonia excretion by the third day of exposure to a pH 9 medium. Unlike B.
      boddaerti, P. schlosseri did not accumulate ammonia in the body at an alkaline pH
      (i.e., pH 9) because it was capable of actively excreting ammonia.
      Periophthalmodon schlosseri did not undergo partial amino acid catabolism (no
      accumulation of alanine) either, although there might be a slight reduction in
      amino acid catabolism in general. The significant decrease in blood pCO(2) in B.
      boddaerti at pH 9 might lead to respiratory alkalosis in the blood. In contrast,
      P. schlosseri was able to maintain its blood pH in BW at pH 9 despite a decrease
      in pCO(2) in the blood. With 8 mM NH(4)Cl in BW at pH 7, both mudskippers could
      actively excrete ammonia, although not to the same extent. Only P. schlosseri
      could sustain ammonia excretion against 8 mM NH(4)Cl in BW at pH 8. In BW
      containing 8 mM NH(4)Cl at pH 9, both mudskippers died within a short period of
      time. Boleophthalmus boddaerti consistently died faster than did P. schlosseri.
      This indicates that the body surfaces of these mudskippers were permeable to
      NH(3), but the skin of P. schlosseri might be less permeable to NH(3) than that
      of B. boddaerti. Both mudskippers excreted acid (H(+)) to alter the pH of the
      alkaline external medium. Such a capability, together with modifications in gill
      morphology and morphometry as in P. schlosseri, might be essential to the
      development of an effective mechanism for the active excretion of NH+4.

PMID- 12794675
TI  - The distribution of mitochondria-rich cells in the gills of air-breathing fishes.
AB  - Respiration and ion regulation are the two principal functions of teleostean
      gills. Mainly found in the gill filaments of fish, mitochondria-rich cells (MRCs)
      proliferate to increase the ionoregulatory capacity of the gill in response to
      osmotic challenges. Gill lamellae consist mostly of pavement cells, which are the
      major site of gas exchange. Although lamellar MRCs have been reported in some
      fish species, there has been little discussion of which fish species are likely
      to have lamellar MRCs. In this study, we first compared the number of filament
      and lamellar MRCs in air-breathing and non-air-breathing fish species acclimated
      to freshwater and 5 g NaCl L(-1) conditions. An increase in filament MRCs was
      found in both air-breathing and non-air-breathing fish acclimated to freshwater.
      Lamellar MRCs were found only in air-breathing species, but the number of
      lamellar MRCs did not change significantly with water conditions, except in
      Periophthalmus cantonensis. Next, we surveyed the distribution of MRCs in the
      gills of 66 fish species (including 29 species from the previous literature) from
      12 orders, 28 families, and 56 genera. Our hypothesis that lamellar MRCs are more
      likely to be found in air-breathing fishes was supported by a significant
      association between the presence of lamellar MRCs and the mode of breathing at
      three levels of systematic categories (species, genus, and family). Based on this
      integrative view of the multiple functions of fish gills, we should reexamine the
      role of MRCs in freshwater fish.

PMID- 12794676
TI  - Effects of body temperature and hydration state on organismal performance of
      toads, Bufo americanus.
AB  - Temperature and humidity are dominant environmental variables affecting
      performance of nocturnal, terrestrial amphibians. Toads are frequently active at
      body temperatures (T(b)) and hydration states (HS) that yield suboptimal
      performance. We investigated the combined effects of T(b) and HS on feeding,
      locomotion, and metabolism of Bufo americanus. More toads responded to the
      presence of prey when fully hydrated than when dehydrated, and times to orient to
      prey, maneuver around a barrier, and reach prey were less in hydrated than in
      dehydrated animals. Time to capture prey decreased with increasing T(b) in fully
      hydrated, but not dehydrated, toads, and hydrated animals caught prey more
      rapidly than did dehydrated animals. Distance traveled in 5 min and aerobic scope
      were affected by T(b). Generally, individuals that performed well in the feeding
      experiments at a particular T(b) and HS also performed well at a different T(b)
      and HS. The same was true for distance traveled and aerobic scope. However,
      within combinations of T(b) and HS, correlations between performance variables
      were minimal. Specialization of a particular variable resulting in high
      performance at a certain T(b) and HS does not appear to exact a cost in terms of
      performance at a different T(b) and HS.

PMID- 12794677
TI  - Temperature and meal size effects on the postprandial metabolism and energetics
      in a boid snake.
AB  - We investigated the combined effect of meal size and temperature on the aerobic
      metabolism and energetics of digestion in Boa constrictor amarali. Oxygen uptake
      rates (Vd2;o2) and the duration of the digestion were determined in snakes fed
      with meals equaling to 5%, 10%, 20%, and 40% of the snake's body mass at 25
      degrees and 30 degrees C. The maximum Vd2;o2 values attained during digestion
      were greater at 30 degrees C than at 25 degrees C. Both maximal Vd2;o2 values and
      the duration of the specific dynamic action (SDA) were attained sooner at 30
      degrees C than at 25 degrees C. Therefore, the temperature effect on digestion in
      Boa is characterized by the shortening of the SDA duration at the expense of
      increased Vd2;o2. Energy allocated to SDA was not affected by meal size but was
      greater at 25 degrees C compared to 30 degrees C. This indicates that a
      postprandial thermophilic response can be advantageous not only by decreasing the
      duration of digestion but also by improving digestive efficiency. Maximal Vd2;o2
      and SDA duration increased with meal size at both temperatures.

PMID- 12794678
TI  - Sexual differences in postingestive processing of dietary protein and
      carbohydrate in caterpillars of two species.
AB  - Previous studies indicated that female Heliothis virescens and Estigmene acrea
      caterpillars use both feeding and postingestive processing as mechanisms to meet
      nutrient demands. We present utilization and nutrient budget data on the
      postingestive partitioning of nutrients into pre- and postabsorptive components.
      Both species utilized carbohydrate efficiently except at very high ingestion
      rates. Of the carbohydrate utilized, more was unaccounted for as intake
      increased, and we assume the material unaccounted for served as a respiratory
      substrate. In contrast, the pattern of nitrogen utilization differed between the
      species. Larval H. virescens efficiently retained nitrogen except at very high
      ingestion rates, whereas E. acrea progressively increased nitrogen egestion in
      response to increased nitrogen ingestion. Overall, females of both species
      utilized nitrogen more efficiently than did males at most ingestion levels, thus
      contributing to the greater protein-derived growth we previously reported. In
      addition, for H. virescens, protein and amino acids accounted for a small
      proportion of fecal nitrogen so that most of the fecal nitrogen was of a
      postabsorptive nature. In contrast, nitrogen excreted by E. acrea could be
      partitioned into both pre- and postabsorptive components. The manner of
      postingestive processing by these two species reflects differences in their
      larval diet.

PMID- 12794679
TI  - Dietary protein content alters energy expenditure and composition of the mass
      gain in grizzly bears (Ursus arctos horribilis).
AB  - Many fruits contain high levels of available energy but very low levels of
      protein and other nutrients. The discrepancy between available energy and protein
      creates a physiological paradox for many animals consuming high-fruit diets, as
      they will be protein deficient if they eat to meet their minimum energy
      requirement. We fed young grizzly bears both high-energy pelleted and fruit diets
      containing from 1.6% to 15.4% protein to examine the role of diet-induced
      thermogenesis and fat synthesis in dealing with high-energy-low-protein diets.
      Digestible energy intake at mass maintenance increased 2.1 times, and composition
      of the gain changed from primarily lean mass to entirely fat when the protein
      content of the diet decreased from 15.4% to 1.6%. Daily fat gain was up to three
      times higher in bears fed low-protein diets ad lib., compared with bears
      consuming the higher-protein diet and gaining mass at the same rate. Thus, bears
      eating fruit can either consume other foods to increase dietary protein content
      and reduce energy expenditure, intake, and potentially foraging time or overeat
      high-fruit diets and use diet-induced thermogenesis and fat synthesis to deal
      with their skewed energy-to-protein ratio. These are not discrete options but a
      continuum that creates numerous solutions for balancing energy expenditure,
      intake, foraging time, fat accumulation, and ultimately fitness, depending on
      food availability, foraging efficiency, bear size, and body condition.

PMID- 12794680
TI  - Body composition changes, metabolic fuel use, and energy expenditure during
      extended fasting in subantarctic fur seal (Arctocephalus tropicalis) pups at
      Amsterdam Island.
AB  - The fasting metabolism of 71- to 235-d-old subantarctic fur seal (Arctocephalus
      tropicalis) pups from Amsterdam Island, southern Indian Ocean, was investigated
      during the long foraging trips of their mothers. Body lipid reserves were
      proportionally greater in female than male pups and higher in postmoult (37%)
      than premoult (10%) animals. The mass-specific rate of mass loss did not differ
      between the sexes but was lower than observed in other species. Daily mass loss
      was estimated to 56% fat, 10% protein, and 34% water. The rate of protein
      catabolism (15 g d(-1)) was negatively related to the size of initial lipid
      stores and accounted for 9% (+/-1%) of total energy expenditure. However, body
      composition changes during the fast were not equal between the sexes, with
      females relying more on protein catabolism than males (11% and 5% of total energy
      expenditure, respectively). Energy expenditure (270 kJ kg(-1) d(-1)) and
      metabolic water production (11.5 mL kg(-1) d(-1)) rates are the lowest reported
      for an otariid species. These results suggest that subantarctic fur seal pups
      greatly reduce activity levels to lower energy expenditure in addition to
      adopting protein-sparing metabolic pathways in order to survive the extreme fasts
      they must endure on Amsterdam Island.

PMID- 12794682
TI  - Designation of the TARP syndrome and linkage to Xp11.23-q13.3 without samples
      from affected patients.
AB  - The Robin sequence is a well-known cause of cleft palate and can be sporadic or
      familial, isolated or syndromic. We present a four-generation family with a
      lethal disorder inherited in an X-linked recessive pattern that includes Talipes
      equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left
      superior vena cava. We have designated this disorder "TARP" syndrome. All
      affected males die in infancy of unknown causes. An X-chromosome linkage scan was
      performed using 14 unaffected members of a single large family and 40 STRP
      markers. The gene was mapped to an 11-cM region in Xp11.23-q13.3. Markers DXS1003
      and DXS8092 flank the region and three-point linkage analyses revealed a maximum
      LOD score of 2.75 at marker DXS1039. We have designated this locus as TARP. This
      locus was mapped without genotyping any affecteds and demonstrates that rare,
      lethal disorders can be evaluated by genetic linkage, even when no affected
      probands are available for study.

PMID- 12794681
TI  - Seasonal adiposity and delayed ovulation in a vespertilionid bat, Scotophilus
      heathi: role of tumor necrosis factor-alpha.
AB  - The aim of this article was to evaluate the physiological significance of tumor
      necrosis factor-alpha (TNF-alpha) in seasonal accumulation of adipose tissue,
      hyperinsulinemia, and anovulation in Scotophilus heathi. The result showed
      seasonal variations in the circulating TNF-alpha level. A higher level of
      circulating TNF-alpha was observed during quiescence and recrudescence, whereas a
      lower level of TNF-alpha was observed during winter dormancy and the preovulatory
      period. An increased circulating TNF-alpha level coincided closely with
      accumulation of adipose tissue and hyperinsulinemia. Immunocytochemical
      localization of TNF-alpha in the ovary showed immunoreactivity mainly in the
      oocytes and theca-interstitial cells. The oocytes of small and medium-sized
      follicles showed strong TNF-alpha immunostaining, whereas weak immunoreactivity
      was observed in the large antral follicles. The atretic follicles showed mild TNF
      alpha immunostaining. TNF-alpha immunoreactivity in the ovary was slightly higher
      during the quiescence and preovulatory periods compared with the periods of
      recrudescence and winter dormancy. TNF-alpha alone significantly increased
      androstenedione and estradiol production by the ovary in vitro but did not
      augment the luteinizing hormone (LH)-induced androstenedione production. However,
      TNF-alpha did augment LH-induced estradiol production. The results of this study
      suggest the involvement of TNF-alpha in the interaction among adipose tissue
      accumulation, insulin resistance, and ovarian activity in S. heathi.

PMID- 12794683
TI  - Dilated cardiomyopathy and new 16 bp deletion in exon 44 of the Dystrophin gene:
      the possible role of repeated motifs in mutation generation.
AB  - Here we report a boy with dilated cardiomyopathy and severe Duchenne muscular
      dystrophy (DMD). The disease-causing mutation was a new 16 bp deletion in exon 44
      of the dystrophin gene, which led to frameshifting and premature translation
      termination. This deletion in exon 44 was associated with dilated cardiomyopathy.
      The dystrophin region in exon 44 might be considered as one of the high-risk
      regions in which mutations could lead to myocardial damage, dilated
      cardiomyopathy, and early death. The abundance of repeated motifs was detected
      within the deleted segment and in the region. These sequence motifs might be
      involved in secondary structure formation and thus they could participate in the
      mutation generation.

PMID- 12794684
TI  - Mutational analysis of the beta- and delta-sarcoglycan genes in a large number of
      patients with familial and sporadic dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is defined by ventricular dilatation associated with
      impaired contractile function. Approximately one-third of idiopathic dilated
      cardiomyopathy cases are due to inherited gene mutations. Mutations in the beta-
      and delta-sarcoglycan genes have been described in limb girdle muscular dystrophy
      and/or isolated DCM. In this study, the aim was to investigate the prevalence of
      these genes in isolated DCM. We screened these two genes for mutations in 99
      unrelated patients with sporadic or familial DCM. The coding exon and intron-exon
      boundaries of each gene were amplified by polymerase chain reaction. Mutation
      analyses were performed by single-strand conformation polymorphism for the beta
      sarcoglycan gene and by direct sequencing for the delta-sarcoglycan gene. New
      polymorphisms, as well as already described ones, were found in these two genes,
      but none appeared to be responsible for dilated cardiomyopathy. We, therefore,
      conclude that these genes are not responsible for idiopathic isolated dilated
      cardiomyopathy in our population. Furthermore, based on previously published and
      present data, we could estimate the prevalence of delta-sarcoglycan gene
      mutations to be less than 1% in idiopathic dilated cardiomyopathy, demonstrating
      that this gene is only marginally implicated in the disease.

PMID- 12794685
TI  - Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene
      causes instability of the respiratory chain complex II.
AB  - A homozygous mutation in the flavoprotein (Fp) gene associated with complex II
      deficiency was demonstrated in a patient with consanguineous parents. She
      succumbed at 5(1/2) months of age following a respiratory infection. The c1664G-
      >A transition detected, predicted the substitution of the small uncharged glycine
      at position 555 by glutamic acid. Her clinical course was at variance with the
      Leigh syndrome in three previously reported patients due to Fp gene mutations. In
      this proband, CRM for flavoprotein as well as iron-containing protein (Ip) was
      decreased, CRM for the entire complex II (130 kDa) being reduced even more. This
      observation prompts speculation of a labile interaction between Ip and Fp
      polypeptides and of a key role of the amino acid at position 555 in the
      interacting domain.

PMID- 12794686
TI  - Long-term follow-up of a new case of liver glycogen synthase deficiency.
AB  - We report a new case of hereditary hepatic glycogen synthase (GS) deficiency (MIM
      240600) in a French Canadian girl referred at 7 years of age for a family history
      of hyperlipidemia. Her initial evaluation incidentally revealed fasting
      hypoglycemia and ketonuria after a 10-hr fast with normal growth, development,
      and physical examination. Additional biochemical findings included fasting
      hypoalaninemia with elevated plasma branched chain amino acids and postprandial
      hyperlactatemia. Liver glycogen synthase activity was reduced. Unlike most other
      reported patients, we observed on three different occasions an increase in
      fasting plasma glucose levels after glucagon administration during episodes of
      hypoglycemia. At 13 years of age, her growth and intellect are normal; however,
      she still has hypoglycemia after 18 hr of fasting. From our patient's course and
      a review of the literature, we conclude: (A) Usual modes of presentation of GS
      deficiency are non-specific symptoms after overnight fasting (7/17), incidental
      findings (3/17), or positive family history (7/17); (B) Most patients maintain
      normal growth (8/11) and intellectual abilities (12/15); (C) Fasting hypoglycemia
      (17/17) and reduced liver glycogen content (9/9) are constant features; (D)
      Biochemical findings also include postprandial hyperlactatemia (13/13), fasting
      hyperketonemia (12/12), and fasting hypoalaninemia (8/9); (E) Glucagon response
      following fasting hypoglycemia is usually reduced or absent (7/8) but can be
      repeatedly present (1/8); (F) Liver steatosis is frequent (6/6). Although rare,
      GS deficiency results in a characteristic biochemical profile that, if
      recognized, should lead promptly to its diagnosis.

PMID- 12794687
TI  - Sialic acid storage disease of the Salla phenotype in American monozygous twin
      female sibs.
AB  - Salla disease, one of three disease phenotypes that manifest increased urinary
      excretion of unconjugated sialic acid, is an autosomal recessive condition caused
      by a mutation in SLC17A5. This gene encodes sialin, a lysosomal membrane
      transporter for sialic acid. Salla disease is rare outside of individuals of
      Finnish ancestry. In this report we describe the disorder in non-Finnish
      monozygous twin siblings, the first reported American cases of Salla disease.

PMID- 12794688
TI  - Biochemical and molecular analyses of infantile free sialic acid storage disease
      in North American children.
AB  - The differential diagnosis of developmental delays and growth retardation in
      early childhood includes the allelic lysosomal sialic acid storage disorders,
      Salla disease and infantile free sialic acid storage disease (ISSD). These
      diseases, due to defective free sialic acid transport out of lysosomes, derive
      from mutations in the SLC17A5 gene coding for the protein sialin. We present two
      patients with clinical, biochemical, and molecular data indicative of lysosomal
      free sialic acid storage disorders. One patient, with a severe clinical course
      typical of ISSD, had 86-fold elevated levels of fibroblast free sialic acid, with
      62% in the lysosomal fraction. His SLC17A5 mutations include a 148-bp deletion of
      exon 9, due to a G >A splice site mutation in position 1 of intron 9, and a 15-bp
      deletion (del 801-815) in exon 6. Another patient, with "intermediate severe"
      Salla disease, had 9-fold elevated levels of free sialic acid in cultured
      fibroblasts, of which 87% resided in the lysosomal fraction. This girl is
      compound heterozygous for the SLC17A5 mutation commonly found in Finnish Salla
      disease patients (R39C) and a 15-bp deletion found in ISSD patients (del 801
      815). These observations emphasize the importance of considering free sialic acid
      disorders in infants with developmental delays and growth retardation, regardless
      of whether they are of Finnish ancestry.

PMID- 12794689
TI  - Glutathione S-transferase Mu null genotype affords protection against alcohol
      induced chronic pancreatitis.
AB  - Glutathione S-transferases (GSTs) play critical roles in providing protection
      against electrophiles and products of oxidative stress, by catalysing the
      formation of glutathione conjugates and by eliminating peroxides. Most
      extensively studied are four main families of human cytosolic GST: GSTAlpha(A),
      GSTMu(M), GSTPi(P) and GSTTheta(T). Absence of GSTM1 or GSTT1 can be attributed
      to absence of the GSTM1 or GSTT1 gene products (null genotype) in approximately
      50% and 20% of the Caucasian population, respectively. We investigated whether
      polymorphisms in the GSTM1, GSTT1 and GSTP1 genes modified the risk for chronic
      pancreatitis (CP). DNA samples were obtained from 142 adult CP patients with
      alcoholic (n = 79), hereditary (n = 21) or idiopathic (n = 42) origin. DNA from
      204 healthy controls and from 57 alcoholic controls was analysed for comparison.
      Patients and controls were all of Caucasian origin. Genetic polymorphisms in GSTs
      were determined by PCR, eventually followed by restriction-fragment-length
      polymorphism analyses in all subjects. The rates of GSTT1 and GSTP1 genotypes did
      not differ between CP patients and healthy controls. However, GSTM1 null
      genotypes were significantly less common in alcoholic CP patients (OR = 0.56, 95%
      CI: 0.33-0.95) as compared to healthy controls and to alcoholic controls (OR =
      0.52, 95% CI: 0.26-1.04). Age- and sex-adjustment bolstered our finding (adjusted
      OR = 0.48, 95% CI: 0.26-0.89). The frequency of the GSTM1 null genotype is
      significantly lower in alcoholic CP patients, especially young female. This
      suggests that GSTM1 null alcohol users, particularly young female, are less
      susceptible to CP.

PMID- 12794690
TI  - Genetic heterogeneity of peroxisome biogenesis disorders among Japanese patients:
      evidence for a founder haplotype for the most common PEX10 gene mutation.
AB  - We, as the only diagnostic center for peroxisome biogenesis disorders (PBD) in
      Japan, identified a total of 31 Japanese patients with PBD during the last 20
      years. They were 27 patients with Zellweger syndrome (ZS), including two sib
      cases, three with neonatal adrenoleukodystrophy (NALD) and one with rhizomelic
      type chondrodysplasia punctata (RCDP). No patient with infantile Refsum disease
      has been detected. These patients were genetically subdivided into
      complementation group A (five ZS and one NALD), B (11 ZS), C (four ZS), E (five
      ZS and two NALD), F (two ZS), and R (one RCDP). They were subjected to mutation
      analysis of PEX1, PEX2, PEX6, PEX7, and PEX10. All the 11 ZS patients with group
      B PBD had a common mutation, i.e., a homozygous 2-base-pair deletion in PEX10. To
      determine whether this highly frequent mutation is due to a founder effect, we
      analyzed single nucleotide polymorphisms within PEX10 among patients and Japanese
      controls. The mutation apparently arose once on an ancestral chromosome in the
      Japanese population. Based on the value of 24 PBD patients identified during the
      last 10 years, we estimated the prevalence of PBD in Japan to be approximately
      one in 500,000 births.

PMID- 12794691
TI  - Prenatal diagnosis of mosaic tetrasomy 8p.
AB  - Tetrasomy 8p is a rare chromosomal disorder that has only been detected in a
      mosaic form. At the present time, 11 cases have been reported; their phenotype
      included agenesis of the corpus callosum, enlarged ventricles, minor facial
      dysmorphism, rib and vertebral anomalies, and mild to moderate developmental
      delay. To the best of our knowledge, tetrasomy 8p has never been prenatally
      diagnosed. This 43-year-old woman was referred for amniocentesis at 20 weeks'
      gestation because of advanced maternal age. Amniotic fluid cells were cultured
      according to standard techniques by the in situ method. A supernumerary
      chromosomal marker was detected in a single clone of cultured amniotic cells and
      interpreted by RHG banding as an isochromosome of the short arm of chromosome 8
      (i(8p)). The ultrasound investigation at 27 weeks gestation revealed enlarged
      ventricles and agenesis of the corpus callosum, which were confirmed at fetal
      autopsy after medical termination of the pregnancy. Chromosomal analyses,
      including RHG banding and FISH, of several tissues showed different levels of
      i(8p) mosaicism. Whereas no i(8p) was detected on cytotrophoblast nor additional
      amniotic fluid cells, 97% and 30% of cells from long-term cultures of placenta
      and lymphocytes, respectively, had the i(8p). Using DNA markers, the
      isochromosome 8p was interpreted as the result of a prezygotic event during
      maternal meiosis. Our findings suggest that the i(8p) is the subject of tissue
      selection. Tetrasomy 8p might be underdiagnosed during pregnancy; therefore,
      karyotyping on a fetal blood sample following detection of agenesis of the corpus
      callosum when no chromosomal abnormality has been found on the amniotic fluid
      cell cultures should be discussed with the parents.

PMID- 12794692
TI  - Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and
      radiological findings in 4 independent families and 3 sporadic cases with
      identified GLI3 mutations.
AB  - Greig cephalopolysyndactyly (GCPS) (OMIM 175700) is an autosomal dominant
      disorder characterized by a distinct combination of craniofacial, hand and foot
      malformations. In this report, clinical and radiological findings of 12 patients
      with GCPS derived from 4 independent families and 3 sporadic cases with
      documented GLI3 mutations are presented with particular emphasis on inter- and
      intrafamilial variability. In a particularly instructive family in which 9
      members of 4 generations could be studied clinically and molecularly, a missense
      mutation (R625W) is transmitted and shows a partially penetrant pattern. In a
      branch of the family, the GCPS phenotype skips a generation via a normal female
      carrier without clinical signs providing evidence that GCPS does not always
      manifest full penetrance as generally supposed.

PMID- 12794693
TI  - Mechanisms of monozygotic (MZ) twinning: a possible role for the cell adhesion
      molecule, E-cadherin.
AB  - Monozygotic (MZ) twins account for about one-third of all twins. Most MZ twins
      arise sporadically but there are familial occurrences. The causes of MZ twinning
      are largely speculative but involve both genetic and environmental factors.
      Genetic factors could include cell adhesion molecules and factors involved in
      growth and differentiation of the placenta and fetus. In this study, we examine
      the possible role of E-cadherin, a cell adhesion molecule, in the causation of
      twinning. A common polymorphism in the E-cadherin gene reduces expression of E
      cadherin by up to 68%. We examined the E-cadherin polymorphism in DNA extracted
      from placental tissue from 121 MZ twins, 99 DZ twins, and 93 singletons. There
      was no significant difference in the distribution of the E-cadherin polymorphism
      in MZ twins although there was a slight over-representation of homozygotes for
      the polymorphism in MZ twins. We conclude that there is insufficient evidence to
      suggest that decreased E-cadherin expression alone is a causative factor in MZ
      twinning but it could be a contributory factor along with other genetic and
      environmental influences.

PMID- 12794694
TI  - US physicians' attitudes toward genetic testing for cancer susceptibility.
AB  - Genetic testing for an inherited susceptibility to cancer is an emerging
      technology in medical practice. Little information is currently available about
      physicians' attitudes toward these tests. To assess US physicians' opinions on
      unresolved issues surrounding genetic testing, a 15-min survey was administered
      to a stratified random sample of 1,251 physicians from 8 specialties, selected
      from a file of all licensed physicians in the US (response rate = 71.0%).
      Dependent measures included physicians' attitudes toward genetic counseling and
      testing qualifications, availability of guidelines, patient confidentiality and
      insurance discrimination issues, and clinical utility of genetic tests. More than
      89% of physicians reported a need for physician guidelines, 81% thought that
      patients with positive genetic test results are at risk for insurance
      discrimination, and more than 53% thought that it was difficult to ensure the
      confidentiality of test results. Almost 25% indicated that genetic tests for
      cancer susceptibility have too many inaccurate or ambiguous results; nearly 75%
      thought that clear guidelines are not available for managing patients with
      positive test results. Only 29% of physicians reported feeling qualified to
      provide genetic counseling to their patients. More than 84% of oncologists
      considered themselves qualified to recommend genetic testing to their patients
      compared with 40% of primary care physicians (PCPs), and 57% of tertiary care
      physicians (TCPs). US physicians expressed great uncertainty about issues
      surrounding genetic testing for cancer susceptibility. Results of this national
      survey underscore the need to provide physicians with clear guidelines on the use
      of genetic cancer susceptibility tests and effective medical training on their
      appropriate implementation.

PMID- 12794695
TI  - Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in
      patients with congenital absence of the uterus and vagina.
AB  - The relationship between cystic fibrosis transmembrane conductance regulator gene
      (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was
      examined. CFTR mutations have previously been associated with congenital
      bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in
      the vas deferens, a Wolffian duct derivative. Because the embryologic development
      of the Mullerian ducts directly depends on the prior normal development of the
      Wolffian ducts, the same gene products may be necessary for normal embryologic
      development of both ductal systems. This study evaluated the role of CFTR
      mutations in the development of CAUV. DNA samples from 25 patients with CAUV were
      tested for the presence of 33 of the most common CFTR mutations. Protein-coding
      DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain
      reaction (PCR) and analyzed for mutations using allele-specific oligonucleotide
      (ASO) probes. Two patients were heterozygous for CFTR mutations. One was
      heterozygous for the W1282X mutation and the other was heterozygous for the
      DeltaF508 mutation. The incidence of the 33 CFTR mutations found in the patients
      with CAUV (8%) was twice that found in the general population (4%), but much less
      than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests
      that it is unlikely for CFTR mutations to cause CAUV in females as they cause
      CBAVD in some males. Furthermore, the data suggest that CAUV in females may be
      the same disorder as CBAVD in males who do not have CFTR mutations.

PMID- 12794696
TI  - Haplotype analysis of the growth hormone releasing hormone receptor locus in
      three apparently unrelated kindreds from the indian subcontinent with the
      identical mutation in the GHRH receptor.
AB  - The growth hormone releasing hormone receptor (GHRHR) plays a critical role in
      growth. We identified three nominally unrelated kindreds harboring the identical
      mutation (E72X) in GHRHR, the gene that encodes GHRHR; all three families
      originated in the Indian subcontinent. Because of the relative geographic
      proximity of these populations, we employed haplotype analysis in the region of
      GHRHR to determine the likelihood that this mutation occurred in a common
      ancestor rather than having occurred on separate occasions in different
      individuals. Members of all three kindreds segregating the E72X mutation were
      genotyped for highly polymorphic dinucleotide repeat microsatellites in a 15.5
      centimorgan (cM) region around GHRHR on chromosome 7p15. We conclude that the
      affected individuals share a common ancestor, and we use the association with
      linked markers to estimate the age of this unique mutation.

PMID- 12794697
TI  - Expression studies of two novel in CIS-mutations identified in an intermediate
      case of Hunter syndrome.
AB  - Hunter syndrome (Mucopolysaccharidosis type II) is a rare X-linked recessive
      lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2
      sulfatase (IDS). To date, more than 200 different mutations have been reported in
      the IDS gene, located on Xq27.3-q28. Here, we report two new mutations (M488I and
      G489A) identified in hemizygosity in an Italian Hunter patient. Their "in vitro"
      expression by COS 7 cells was carried out in order to evaluate their functional
      consequence on enzyme activity as well as their possible cumulative effect on the
      malfunctioning of the protein. The results obtained enabled us to confirm the
      G489A mutation as causative. The M488I mutation, however, could not be
      unequivocally considered as causing disease because of its residual activity.
      Although a cumulative effect of the two mutations can be excluded "in vitro," we
      are cautious about drawing a conclusion with regard to the possible role that the
      two mutations could have played "in vivo" in modulating the phenotype of the
      patient. Finally, the knowledge of the molecular defect of the patient has
      enabled us to identify the carriers, providing reliable genetic counselling to
      the females of the family.

PMID- 12794698
TI  - Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia.
AB  - Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3
      gene. FGFR3 is known to play a role in controlling nervous system development. We
      describe the clinical and neuroradiological findings of the first two patients,
      to our knowledge, affected by HCH and MS, respectively, in whom bilateral
      dysgenesis of the medial temporal lobe structures has been observed. In both
      patients diagnosis was confirmed by molecular analysis. They were mentally normal
      and showed similarities in early-onset temporal lobe-related seizures. In both
      patients EEG recorded bilateral temporal region discharges. MRI detected temporal
      lobe anomalies with inadequate differentiation between white and gray matter,
      defective gyri, and abnormally shaped hippocampus.

PMID- 12794699
TI  - Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital
      chylothorax, and congenital pulmonary lymphangiectasia.
AB  - We report a female infant with congenital lymphedema, facial anomalies,
      intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At
      birth the patient presented with severe respiratory distress due to nonimmune
      hydrops fetalis, a congenital chylothorax (CC), and pulmonary lymphangiectasia.
      Hydrops fetalis may be present in newborns with the Hennekam syndrome.
      Lymphoscintigraphy can be useful in explaining pleural-pulmonary involvement of
      this generalized lymph vessel malformation syndrome.

PMID- 12794700
TI  - Fetus with an unusual form of nonrhizomelic chondrodysplasia punctata: case
      report and review.
AB  - Chondrodysplasia punctata (CDP) is a heterogeneous condition mainly characterized
      by premature and ectopic calcification of cartilage. Many genetic and nongenetic
      causes have been described leading to a preliminar etiological classification
      into defects of peroxisomal metabolism, defects in cholesterol metabolism, and
      vitamin K (vit K) metabolism. However, numerous cases of CDP still remain
      unclassified. The difficulties in reaching a causal diagnosis are illustrated
      here by a 23-week-old fetus with nonrhizomelic CDP characterized by extensive
      cartilage stippling, brachyphalangy, and nasal hypoplasia.

PMID- 12794701
TI  - Unique insertional translocation in a childhood Wilms' tumor survivor detected
      when his daughter developed bilateral retinoblastoma.
AB  - Retinoblastoma and Wilms' tumor are rare childhood embryonic tumors associated
      with loss or inactivation of tumor suppressor genes, RB1 located within 13q14,
      and WT1 located within 11p13. Interchromosomal insertional translocations occur
      rarely, and such rearrangements within RB1 or WT1, even rarer. We report a unique
      family in which an insertional translocation of a chromosomal segment that
      included band 13q14 inserted into 11p13 caused childhood Wilms' tumor in the
      father, and whose child developed bilateral retinoblastoma. This is the first
      case of an insertional translocation that caused both tumors. This insertional
      translocation had significant consequences for genetic counseling and in utero
      diagnosis. The estimated risk for an offspring of this father to develop Wilms'
      tumor is up to 50%, to develop retinoblastoma up to 25%, to have neither tumor
      25%, and to have both tumors 0%.

PMID- 12794702
TI  - Delineation of a newly recognized neurocutaneous malformation syndrome with
      "cutis tricolor".
AB  - The term "cutis tricolor" describes the combination of congenital hyper- and hypo
      pigmented lesions, in close proximity to each other with a background of normal
      skin. Cutis tricolor represents twin spotting and has been reported as an
      isolated skin disorder or as part of a neurocutaneous malformation syndrome. We
      report on an 11-year-old girl with diffuse pigmentary changes of the cutis
      tricolor type, facial anomalies, mental retardation, epileptic seizures, EEG
      anomalies, small skull, progressive double-curved thoracolumbar/lumbar scoliosis
      with vertebral scalloping and dysplastic vertebral pedicles and ribs, and tibial
      bowing. These abnormalities are similar to those observed in cases reported by
      Happle et al. [1997: J Med Genet 34:676-678] and Ruggieri [2000: Eur J Pediatr
      159:745-749]. Additionally, our patient had altered behavior and hypoplasia of
      the corpus callosum. This constellation of abnormalities represents a newly
      recognized neurocutaneous malformation syndrome. The phenotype could be explained
      by somatic mutation. Loss of heterozygosity at an early developmental stage would
      give rise to one single mosaic skin disorder (e.g., generalized skin
      manifestations of the cutis tricolor type in association to extracutaneous
      anomalies). Postzygotic recombination occurring later during embryogenesis would
      give rise to solitary lesions confined to the skin.

PMID- 12794703
TI  - 14q(22) deletion in a familial case of anophthalmia with polydactyly.
AB  - We report a family of anophthalmia with ocular and extraocular manifestations.
      The proband, his three sisters, and two sons had anophthalmia and preaxial
      polydactyly in the right hand. Cytogenetic analysis was done for the proband and
      two of his sons, one of whom was affected. Another male child was affected but
      was not available for cytogenetic analysis. Karyotypes of both affected
      individuals showed deletion on long arm of 14q22q23. Literature review shows four
      cases of anophthalmia with extra ocular anomalies associated with 14q (q22q23)
      deletion. Recently it has been suggested that the human homeobox gene, SIX6, and
      the BMP-4 gene are responsible for eye development. Both are located in the
      chromosome 14q22.3-q23 region. Deletion in this region has been known to be
      associated with anophthalmia and pituitary anomalies. This is the first family of
      anophthalmia, which showed polydactyly with a chromosomal deletion in the 14q22
      q23 region and its familial transmission in two generations with a total of six
      affected individuals.

PMID- 12794704
TI  - Inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) with manifestations of partial
      duplication 4p and Wolf-Hirschhorn syndrome.
AB  - An 8-year-old girl with a combination of clinical manifestations of partial
      duplication 4p and the Wolf-Hirschhorn syndrome was studied. Chromosomal G
      banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at
      4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf
      Hirschhorn syndrome critical region). The chromosomes of the parents were normal.
      Her karyotype was thus 46,XX, inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) de
      novo. The inverted duplication deletion was assumed to have arisen through
      chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a
      dicentric intermediate, breakage of the dicentric to result in a monocentric, and
      telomere capture/healing of the broken end. Olfactory receptor gene clusters at
      4p16.3 were ruled out as an intermediary of the duplication deletion process.

PMID- 12794706
TI  - Role of selected mutations in exon 28 and 39 of Myosin15 gene in autosomal
      recessive nonsyndromic sensorineural deafness among affected South Indian
      families.

PMID- 12794705
TI  - Molecular characterization of a patient with central nervous system
      dysmyelination and cryptic unbalanced translocation between chromosomes 4q and
      18q.
AB  - We report on a 12-year-old boy who presented with delayed development and CNS
      dysmyelination. Genetic studies showed a normal 46,XY karyotype by routine
      cytogenetic analysis, and 46,XY.ish del(18)(q23)(D18Z1+, MBP-) by FISH using a
      locus-specific probe for the MBP gene (18q23). Though the patient appeared to
      have normal chromosome 18s by repeated high resolution banding analysis, his
      clinical features were suggestive of a deletion of 18q. These included hearing
      loss secondary to stenosis of the external auditory canals, abnormal facial
      features, and foot deformities. FISH studies with genomic probes from 18q22.3 to
      18qter confirmed a cryptic deletion which encompassed the MBP gene. In an attempt
      to further characterize the deletion, whole genome screening was conducted using
      array based comparative genomic hybridization (array CGH) analysis. The array CGH
      data not only confirmed a cryptic deletion in the 18q22.3 to 18qter region of
      approximately 7 Mb, it also showed a previously undetected 3.7 Mb gain of 4q
      material. FISH studies demonstrated that the gained 4q material was translocated
      distal to the 18qter deletion breakpoint. The 18q deletion contains, in addition
      to MBP, other known genes including CYB5, ZNF236, GALR1, and NFATC1, while the
      gained 4q material includes the genes FACL1 and 2, KLKB1, F11 and MTNR1A. The use
      of these combined methodologies has resulted in the first reported case in which
      array CGH has been used to characterize a congenital chromosomal abnormality,
      highlighting the need for innovative molecular cytogenetic techniques in the
      diagnosis of patients with idiopathic neurological abnormalities.

PMID- 12794707
TI  - Carrier frequency of the RSH/Smith-Lemli-Opitz IVS8-1G>C mutation in African
      Americans.

PMID- 12794708
TI  - Patient with a deletion of chromosome 21q and minimal phenotype.

PMID- 12794709
TI  - Margareta Mikkelsen.
AB  - Margareta Mikkelsen, a well-known Danish cytogeneticist, started to research
      autosome aberrations in 1959 and built the first chromosome laboratory at the
      University of Copenhagen with Anders Froland. In 1968, she developed a fully
      functional chromosome laboratory from scratch at the John F. Kennedy Institute
      (JFKI). Not only the laboratory performed diagnoses all over Denmark, but also it
      is a sole place among all the departments of human genetics to train Danes to be
      clinical geneticists. A generation of Danish geneticists grew up under Dr.
      Mikkelsen's wing. Dr. Mikkelsen played a pioneering role in research on Down
      syndrome (DS) and exploring the source of the extra chromosome 21 remains her
      main interest. She performed the first case of prenatal diagnosis by
      amniocentesis in Denmark and since then, she was active in this field. The JFKI
      also committed to research on the fragile X syndrome. Dr. Mikkelsen took on many
      public responsibilities in Denmark and in Europe. She was on the board of many
      Danish scientific organizations and an active member of the European Society of
      Human Genetics (ESHG). She was efficient in public education with communication
      in lay language. After her retirement, she was more dynamic in medical ethics.
      Born as Irmtraud Wieser in Munich, Dr. Mikkelsen walked through the hardship of
      pre-war Germany, the inferno of the World War II, the trauma brought by her two
      husbands' alienation, the obstacles in work, and physical ailment to fulfill her
      unwavering commitment to human genetics.

PMID- 12794710
TI  - Depletion of mitochondrial DNA in HIV-1-infected patients and its amelioration by
      antiretroviral therapy.
AB  - Mitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected
      from Human immunodeficiency virus 1 (HIV-1)-infected patients and healthy
      controls were measured longitudinally using real-time polymerase chain reaction
      to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and
      to assess the value of monitoring mtDNA in PBMCs to predict adverse events
      amongst these patients. MtDNA levels in PBMCs were significantly decreased in
      treatment-naive HIV-1-infected patients compared with healthy people. MtDNA
      levels were not only significantly correlated with CD4(+) T-cell count, but also
      inversely correlated with HIV-1 viral load. MtDNA levels in untreated patients
      and healthy controls were stable during the period of observation. On the other
      hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA
      increased during treatment and recovered to levels comparable to healthy
      controls. In contrast, mtDNA decreased immediately after the initiation of an
      AZT/ddC-containing regimen. We did not find a correlation between mtDNA levels
      and changes in clinical parameters. There was no significant difference in mtDNA
      levels between patients with and those without lipoatrophy. Furthermore, there
      was no obvious difference in mtDNA levels amongst those patients exhibiting signs
      and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA
      levels in PBMCs amongst HIV-1-infected patients and its amelioration by
      antiretroviral therapy may suggest the influence of direct effects on
      mitochondria or mtDNA by HIV-1 infection. Further investigations are needed to
      elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA
      measurement in the care of HIV-1-infected individuals.

PMID- 12794711
TI  - Immunological recovery despite virological failure is independent of human
      immunodeficiency virus-type 1 resistant mutants in children receiving highly
      active antiretroviral therapy.
AB  - Relationships between human immunodeficiency virus-type-1 (HIV-1) drug-resistant
      mutants and immunological recovery were investigated after 12-week antiretroviral
      therapy in 43 children infected perinatally with virological failure. Twenty-two
      children received highly active antiretroviral therapy (HAART) and 21 received
      double therapy with reverse transcriptase inhibitors. At baseline, no difference
      in reverse transcriptase or protease inhibitors resistant mutants was present
      among the groups. After 12 weeks, the two groups were similar regarding
      proportion of children with reverse transcriptase resistant mutants. Sixteen
      (73%) HAART-treated children, but no child receiving double therapy had HIV-1
      with primary resistance mutations to protease inhibitors. Secondary protease
      mutations were found in all HAART-treated and in 17/21 (81%) children receiving
      double therapy. The mutation numbers in reverse transcriptase or protease genes
      were significantly higher after HAART than after double therapy. Nevertheless, 12
      (55%) of HAART-treated children (but no child receiving double therapy) showed
      immunological recovery. The frequency and number of mutations were similar in
      HAART-treated children with or without immunological recovery both at baseline
      and after 12 weeks. The findings suggest, immunological recovery notwithstanding,
      virological failure is independent of drug-resistant mutations and consequent
      possible changes in viral fitness.

PMID- 12794712
TI  - Saccharomyces cerevisiae-derived HBsAg preparations differ in their attachment to
      monocytes, immune-suppressive potential, and T-cell immunogenicity.
AB  - Expression of the hepatitis B virus S protein results in the formation of a
      lipoprotein particle, the hepatitis B surface antigen (HBsAg). Such particles,
      produced in Saccharomyces cerevisiae, bind to the cell surface of monocytes
      through interaction with the lipopolysaccharide binding protein and the
      lipopolysaccharide receptor, CD14. This attachment is suggested to depend on the
      presence of charged phospholipids in the particles. In addition, such particles
      interfere with the lipopolysaccharide and interleukin-2-induced activation of
      monocytes. In the present study, it is reported that of three Saccharomyces
      cerevisiae-derived HBsAg preparations, two have a reduced capacity to bind to
      monocytes. A correlation with a reduced potential to inhibit the
      lipopolysaccharide-induced activation of monocytes and an increased potential to
      stimulate HBsAg-specific T-cell proliferation is observed. Surprisingly,
      differences in phospholipid content that might explain these observations, were
      not detected.

PMID- 12794713
TI  - Molecular epidemiology and transmission of hepatitis B virus in close family
      contacts of HBV-related chronic liver disease patients.
AB  - There is limited data on the patterns of HBV mutation in family contacts of
      chronic liver disease (CLD) patients in India. DNA sequence analysis is an
      important tool to study this viral epidemiology. Transmission and prevalence of
      mutations in the S and pre-C gene region in HBV infected close family contacts of
      HBV-related CLD patients were studied. Twelve HBsAg(+) index patients and their
      20 HBV DNA contacts were studied in detail. The S ORF and the pre-C region were
      sequenced using direct PCR products. S-gene sequencing included 32 specimens (12
      index cases and all 20 contacts). Pre-C gene sequencing included 26 specimens (12
      index cases and all the 14 HBsAg(+) contacts irrespective of their HBeAg status).
      More than 98% sequence homology was found between the index patients and their
      contacts. The in-depth study of 12 families revealed that the transmission
      pattern was primarily horizontal in 6 (50%) and vertical in 2 (17%) families (P <
      0.05). The remaining four families had evidence of both horizontal and vertical
      transmission. Mutations in the S-gene were found in 80% of HBsAg(+) and 17%
      HBsAg(-) subjects (P < 0.05). A total of 22-point mutations at different
      nucleotide positions were found. In these, 16 (72%) were mutation of the "a"
      determinant region and 14 (64%) resulted in missense mutations. The commonest S
      gene mutations were T118V and A128V, present in 44 and 38% specimens,
      respectively. T143M and G145R mutations in the second loop of the "a" determinant
      were found in 9% of the specimens. Novel mutations, C137stp and C138stp were
      found in only one HBsAg(-) subject. Mutations in the pre-C gene were common (91%)
      in patients with HBeAg(-) phenotype. G1896A mutation was found in 7 of 11 (64%)
      specimens changing amino acid tryptophane (W) to stop codon. Other mutations were
      at codons 25 and 29. The results of the study, demonstrate (1) clustering of Pre
      C and S-gene mutations in the families, (2) horizontal mode of transmission and a
      common source infection appears to be frequent as evidenced by sequence homology
      and detailed history, (3) T118V and A128V were the commonest mutations in the S
      gene region, while (4) M2 (G1896A) was the commonest pre-C gene mutation, and (5)
      long-term follow-up evaluation of these mutations suggested.

PMID- 12794714
TI  - Genotypes and phylogenetic characterization of hepatitis B and delta viruses in
      Egypt.
AB  - Hepatitis B virus (HBV) and hepatitis D virus (HDV) sequences among HBV carriers
      from Egypt have not been evaluated sufficiently. The genotypes of HBV isolated
      from 105 serum samples from Egyptian carriers were determined. Four complete
      genomes and 11 entire preS1/S2/S genes were sequenced and evaluated. All serum
      samples were classified into HBV genotype D using serologic and genetic methods.
      The length of four complete nucleotide sequences was 3,182 bp. In all 15 samples,
      the common 33 nucleotides (11 amino acids) deletions in the preS1 region specific
      for HBV genotype D were observed. In the phylogenetic analysis based on the
      complete nucleotide sequences, all samples were clustered with the HBV isolates
      reported from previously Western and Mediterranean countries with nucleotide
      homology ranging from 96.0-98.0%. Of 75 HBsAg positive samples, anti-HDV was
      found in 15 (20%), and HDV RNA was detected in 9 of 15 (60%). The proportion of
      the patients with liver disease was higher in HBV carriers of anti-HDV positive
      with HDV RNA than in HBV carriers of anti-HDV positive without HDV RNA (P <
      0.05). In the phylogenetic analysis based on the sequences in nucleotide position
      853-1267 of HDV, nine samples were classified into HDV genotype I with the
      nucleotide homology ranging from 88.3-92.1% (mean; 90.5%) and clustered with HDV
      strains reported previously from Ethiopia, Somalia, Egypt, and Lebanon. These
      results indicate that HBV genotype D and HDV genotype I are most prevalent in
      Egypt, and HDV co-infection in HBV carriers is related to severity of liver
      disease.

PMID- 12794715
TI  - Influence of hepatitis B virus genotypes on the development of preS deletions and
      advanced liver disease.
AB  - Hepatitis B virus (HBV) mutants with deletions in the preS region have not been
      evaluated for association with viral genotypes. In a case-control study, HBV DNA
      samples collected from 80 each of carriers infected with HBV genotype B or C were
      examined for preS deletions. PreS deletion mutants were found in a total of 37 of
      160 (23%) HBV carriers. Carriers with preS deletion mutants were older (56.0 +/-
      12.7 vs 49.3 +/- 16.9 years, P < 0.05), were infected more frequently with HBV
      genotype C (84% vs 40%, P < 0.05), and had more advanced disease, such as liver
      cirrhosis and hepatocellular carcinoma (54% vs 31%; P < 0.05), than did those
      without such mutants. In a multivariate analysis, genotype C (odds ratio [OR] =
      9.3, P < 0.001) and advanced liver disease (OR = 3.1, P < 0.01) were the most
      significant variables in association with preS deletions. A direct repeat
      sequence (TCAGG) was found at the start or at the end of preS1 deletions in 6 of
      the 20 (30%) cases examined, and preS2 deletions in these cases were clustered
      over the 5'-terminal half of this region. These results indicate that the
      development of preS deletion mutants depends on HBV genotypes and that it may be
      associated with progressive liver disease.

PMID- 12794716
TI  - A case-control study for early prediction of hepatitis B e antigen seroconversion
      by hepatitis B virus DNA levels and mutations in the precore region and core
      promoter.
AB  - Factors influencing and predictive of seroconversion from hepatitis B e antigen
      (HBeAg) to antibody (anti-HBe) were sought in a case-control study of 61 patients
      with chronic hepatitis B who had been observed from 5 years before to 1 year
      after seroconversion, and 32 patients who did not seroconvert during the entire 6
      year period. Almost all of the patients (96%) were infected with HBV genotype C.
      HBV DNA levels began to decrease 3 years before seroconversion in the
      seroconverters, while they remained high in the non-converters. The frequency of
      precore mutation and the loss of HBeAg (A1896) started to increase 1 year before
      in the converters, and became significantly higher at seroconversion (23 vs. 3%,
      P = 0.030) than that in the non-converters. Double mutation in the core promoter
      (T1762/A1764) was more common in the seroconverters than in the non-converters 5
      years before seroconversion (48 vs. 28%), and became significantly more frequent
      at seroconversion (65 vs. 41%, P = 0.046). Seroconversion occurred in 75% of the
      patients with at least HBV DNA levels <5.5 logarithmic equivalents/mL; precore
      mutation in 20% or more of HBV DNA; or core promoter mutation. Seroconversion
      occurred in 50% of those patients within 1 year, 88% within 2 years, and 93%
      within 5 years. These results indicate that a decrease in HBV DNA levels and
      mutations in the precore region and the core promoter were associated
      significantly and complementarily with seroconversion, and each of them or a
      combination thereof was predictive of seroconversion years ahead.

PMID- 12794717
TI  - Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic
      chemotherapy: a prospective study.
AB  - Breast cancer is a rapidly increasing problem in many developing countries, and
      cytotoxic chemotherapy is now an integral part of its management. In several
      developing countries, the carriage of hepatitis B virus (HBV) in cancer patients
      may be as high as 12%, and such patients are at risk of developing fatal HBV
      reactivation during chemotherapy. HBV reactivation is well recognized in patients
      with hematological malignancies, but limited data are available on patients with
      other, more common, cancers, such as breast cancer. Recent data have suggested
      that increased viral replication, an indication of HBV reactivation, may precede
      clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation
      during chemotherapy may have been underestimated. In this prospective study,
      breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive
      were followed up during chemotherapy. The main objectives were to determine the
      incidence of HBV reactivation in breast cancer patients undergoing conventional
      chemotherapy; to investigate whether "serial HBV DNA monitoring" improves the
      accuracy of diagnosing HBV reactivation when compared with previous schema that
      only measured HBV DNA at the time of clinical hepatitis ("conventional
      monitoring"); and to assess the clinical consequences as a result of developing
      the condition. The secondary objective was to identify risk factors associated
      with this condition. Over an 18-month period, 41 patients were studied. Ten
      developed HBV reactivation by conventional monitoring criteria, but with serial
      HBV DNA monitoring, seven additional patients were diagnosed when increased HBV
      DNA levels were detected before, but not concomitant with, clinical hepatitis.
      Thus, a total of 17 patients (41%) developed HBV reactivation. Premature
      termination of chemotherapy or delay in treatment schedules occurred in 71% of
      the patients who developed viral reactivation, as compared with 33% in those who
      did not develop the condition (P = 0.019). No risk factors associated with the
      development of HBV reactivation could be identified. Serial monitoring of HBV
      DNA, in addition to liver function, increases the sensitivity of diagnosing of
      HBV reactivation, and helps explain some cases that would otherwise be labeled as
      "cryptogenic hepatitis," for which concomitant HBV DNA measured at the time of
      hepatitis was undetectable. The present study highlights the importance of
      monitoring HBsAg-seropositive patients who are receiving chemotherapy for common
      solid tumors such as breast cancer.

PMID- 12794718
TI  - Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN
      gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B.
AB  - The pathogenesis of hepatitis C virus-induced chronic liver disease is still
      poorly understood. Previous studies revealed enhanced hepatic expression of the
      Th1 prototype cytokine IFN-gamma in individuals with chronic hepatitis C. In
      accordance with several animal models of experimentally induced hepatitis, a Th1
      lymphocyte driven inflammatory process, which involves newly infiltrated as well
      as resident monocytes/macrophages, has been proposed. An involvement of the
      interferon-gamma-inducible chemokine IP-10, which is chemoattractive for
      stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic
      mouse model, a reduction of hepatic infiltration and liver disease was achieved
      recently by administration of antibodies directed against the interferon-gamma
      inducible chemokine Mig and against IP-10. In the present study, expression of IP
      10 was investigated both in serum and in the liver of patients with chronic
      hepatitis C and hepatitis B. Patients with liver diseases of non-viral etiologies
      served as controls. IP-10 expression was highest in hepatitis C. In chronic
      hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to
      viral infections, IP-10 expression was strongly correlated with the amount of
      transcripts for IFN-gamma and to the amount of transcripts for the constitutively
      expressed macrophage derived cytokine IL-18. Hepatic inflammatory activity,
      however, was found to be associated more closely with IFN-gamma than with IP-10
      or IL-18 mRNA expression. The data support the hypothesis that IP-10 is
      responsible for the recruitment of Th cells and monocytes in chronic hepatitis C,
      and suggest that its role in chronic hepatitis B is less determining. Moreover,
      they deliver additional support for the view that IFN-gamma still has to be
      considered as a mediator that determines the outcome of inflammation, e.g., via
      its ability to activate IL-18 expressing cells and to initiate a delayed type
      hypersensitivity reaction.

PMID- 12794719
TI  - Distribution of hepatitis B virus in the liver of chronic hepatitis C patients
      with occult hepatitis B virus infection.
AB  - Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the
      absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C,
      its characteristics are not well known. In this work, the presence of HBV-DNA (by
      polymerase chain reaction; PCR) and its distribution (by in situ hybridization)
      in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients
      with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic
      carriers were determined. The results showed that serum HBV-DNA levels were
      statistically lower (P = 0.001) in patients with occult HBV infection than in
      HBsAg chronic carriers. The HBV infection pattern in liver cells was identical
      between patients with occult HBV infection and those with chronic hepatitis B.
      However, the mean percentage of HBV-infected hepatocytes was significantly lower
      (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg
      chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have
      HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV
      infection. In conclusion, patients with occult HBV infection have a low number of
      HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection
      and low viremia levels found in these cases.

PMID- 12794720
TI  - Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of
      chronic HCV-infected and non-alcoholic steatohepatitis patients.
AB  - To investigate the intra-hepatic activation of the IFN system in patients
      affected by chronic HCV-infection in comparison with that observed in a non
      infectious liver disease such as non-alcoholic steatohepatitis, we measured the
      liver steady state mRNA levels of interferon-alpha, interferon-beta and
      interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5
      AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of
      these parameters with viral load and liver injury were also analyzed. Twenty-four
      chronic untreated HCV-infected subjects and seven patients with non-alcoholic
      steatohepatitis were enrolled in the study. Liver biopsies were graded according
      to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were
      assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic
      steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were
      significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA
      were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated
      positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated
      induction of these genes. Although plasma viral load was correlated inversely
      with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma
      and IRF-1 mRNA levels were correlated positively with ALT, but not with the
      grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in
      livers with lower staging scores. These findings support the hypothesis that in
      chronic HCV infection there is an imbalance between an upregulated IFN-gamma
      system and a downregulated IFN-alpha and -beta system, probably due to a mixed
      effect exerted by HCV-specific and inflammatory non-specific factors.

PMID- 12794721
TI  - Production of interleukin-18 and interleukin-12 in patients suffering from
      chronic hepatitis C virus infection before antiviral therapy.
AB  - Interleukin-12 and -18 (IL-12 and IL-18) are known to enhance the cytotoxic T
      lymphocyte response synergistically, but their precise involvement in hepatitis C
      virus (HCV) infection is not well known, especially for IL-18. Enzyme-linked
      immunosorbent assay (ELISA) was used to study the production of these cytokines
      in plasma and peripheral blood mononuclear cells (PBMCs) stimulated by
      lipopolysaccharide (LPS) of patients infected chronically with HCV before
      initiation of antiviral therapy. Fifty-six patients and 40 healthy controls were
      evaluated. Patients infected with genotype 1 or with genotype other than genotype
      1 HCV had significantly a high production of plasma IL-12 compared with controls
      (P < 0.05). However, patients infected with genotype 1 HCV had lower levels of
      PBMC IL-18 than were founded in the controls (P < 0.05); plasma IL-18 also tended
      to be lower in this group of patients than in the controls, although
      nonsignificantly. Plasma IL-18 was related to hepatic histological activity (P <
      0.05). The data suggest a relationship between these two cytokines and some
      features of HCV infection, so that their respective production in relation to the
      outcome of the infection deserves further study.

PMID- 12794722
TI  - Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of
      Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and
      genotypic influence.
AB  - The association between cryoglobulinemia and hepatitis C virus (HCV) infection
      has been reported. However, the factors underlying its wide variation of
      occurrence have not yet been well identified. To investigate this,
      cryoglobulinemia was studied in four cohorts of Egyptian and Japanese patients.
      Fifty Egyptian patients with chronic hepatitis C, infected with genotype 4 (the
      predominant HCV genotype in Egypt), were compared with 50 age- and sex-matched
      Japanese patients, infected with HCV genotype 1b (the predominant HCV genotype in
      Japan). Thirty-two Egyptian and 30 age- and sex-matched Japanese patients with
      chronic hepatitis B were included as controls. All patients were noncirrhotic.
      Antinuclear antibody (ANA), immunoglobulins (Ig), and cryoglubulins were
      assessed. Results showed a significantly higher prevalence of cryoglobulinemia in
      chronic hepatitis C Japanese genotype 1b (40%) as compared with Egyptian genotype
      4 (14%), P = 0.003, while no difference was found between Japanese (17%) and
      Egyptian chronic hepatitis B controls (13%). Symptomatic cryoglobulinemia was
      more prevalent in the Japanese than in the Egyptian chronic hepatitis C group
      (10% vs. 4%), but the difference was not statistically significant. Univariate
      analysis showed no association between cryoglobulinemia and either age, sex,
      alanine aminotransferase level, or HCV viral load in Japanese or Egyptian
      patients, while the mean IgM level was significantly higher in the cryoglobulin
      positive than in the cryoglobulin-negative chronic hepatitis C patients in each
      group (P = 0.003 and 0.017, respectively). Cryoglobulinemia was found to be
      significantly associated with both high IgG level (P = 0.020), and positive ANA
      (P < 0.001) in Japanese patients with chronic hepatitis C, genotype 1b but not in
      Egyptians with genotype 4. Multivariate analysis showed that the only factors
      predisposing to cryoglobulinemia were Japanese ethnicity with HCV genotype1b (P =
      0.002, OR = 2.56), high IgM level of >245 mg/dl (P = 0.018, OR = 2.05) and female
      gender (P = 0.040, OR = 1/0.66). In conclusion, cryoglobulinemia is prevalent in
      Japanese patients with chronic hepatitis C infected with genotype 1b, but
      cryoglobulinemia is not common in Egyptians with HCV genotype 4. Although it was
      not possible to evaluate ethnicity and HCV genotype separately in this study, HCV
      genotype 1b appears to predispose more to cryoglobulinemia than does genotype 4.
      Female gender and high serum IgM level were also related.

PMID- 12794723
TI  - Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal
      arterial walls in healthy individuals in China.
AB  - Several studies have demonstrated that BK virus (BKV) and JC virus (JCV)
      establish latent infection in peripheral blood leukocytes (PBLs) of healthy
      individuals; however, the main populations studied are European. In this study,
      the prevalence of BKV and JCV DNA in PBLs from healthy adult individuals and
      umbilical cord blood from newborn children in China was detected by semi-nested
      polymerase chain reaction (snPCR) followed by restriction enzyme analysis. The
      results suggest that the healthy adult Chinese population harbors BKV and JCV DNA
      in peripheral leukocytes. Overall, the prevalence of BKV and JCV DNA in PBLs of
      healthy adult individuals was 42.1% and 7.8%, respectively. The overall
      prevalence of BKV DNA was significantly higher than that of JCV DNA. None of the
      umbilical cord blood samples from newborn children were positive for BKV and JCV
      DNA. To understand further the target tissues involved in establishment of BKV
      and JCV latency in healthy individuals, the presence of DNA from both viruses was
      detected in normal arterial wall samples from 20 young trauma victims by the same
      method used for leukocyte DNA. BKV DNA was detected alone in 20% of samples
      tested; JCV DNA was not detected alone in any of the samples. DNA from both
      viruses was found in 5% of samples. This is the first report to show that normal
      arterial walls of healthy individuals may be another target site of latency for
      BKV and JCV.

PMID- 12794724
TI  - Coxsackievirus B3 sequences in the blood of a neonate with congenital
      myocarditis, plus serological evidence of maternal infection.
AB  - A fatal case of myocarditis in a neonate is described. The clinical features were
      evident at birth, and enteroviral RNA was detected in the blood of the baby on
      the day of birth and again 10 days later by a generic enterovirus nested reverse
      transcription-polymerase chain reaction (RT-PCR) assay. The enterovirus RNA was
      subsequently retested by a separate, newly developed nested RT-PCR assay yielding
      a PCR product within the VP1 coding region suitable for sequencing. Identical 239
      base pair sequences were obtained from the RNA of the two blood samples and this
      sequence most closely resembled coxsackievirus B3 (94% identity). The baby's
      mother was pyrexial immediately postpartum and an early antenatal serum and a
      serum sample collected 10 days postpartum tested in parallel for enterovirus IgM
      antibody showed negative to strong-positive seroconversion. Infection of the
      mother was the likely primary event with in utero transfer of the virus to the
      fetus in the last few days of pregnancy. Neonatal blood is a valuable specimen
      for enterovirus diagnosis by RT-PCR. A newly developed nested RT-PCR assay was
      successful in typing the enterovirus from stored RNA extracted directly from the
      blood samples. Serology for enterovirus IgM antibody can be useful for
      convalescent diagnosis of enterovirus infection in the mother, especially with
      earlier serum for comparison.

PMID- 12794725
TI  - Tissue plasminogen activator induced by dengue virus infection of human
      endothelial cells.
AB  - Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe
      complications of dengue virus (DV) infection. However, the pathogenesis of
      hemorrhage induced by dengue virus infection is poorly understood. Since
      endothelial cells play a pivotal role in the regulation of hemostasis, we studied
      the effect of DV infection on the production of tissue plasminogen activator
      (tPA) and plasminogen activator inhibitor 1 (PAI-1) in vitro using both primary
      isolated endothelial cells, human umbilical cord veins cells, and a human
      microvascular endothelial cell line. DV infection significantly induced the
      secretion of tPA but not PAI-1 of human endothelial cells. In addition, tPA mRNA
      of endothelial cells was induced by DV as demonstrated by RT-PCR. Antibody
      against IL-6 but not control antibody inhibited DV-induced tPA production of
      endothelial cells. Furthermore, a good correlation between sera levels of IL-6
      and tPA was found in DHF but not DF patients. These results suggest that IL-6 can
      regulate DV-induced tPA production of endothelial cells, which may play important
      roles in the pathogenic development of DHF/DSS.

PMID- 12794726
TI  - Measurement of EBV-IgG anti-VCA avidity aids the early and reliable diagnosis of
      primary EBV infection.
AB  - Current serological methods for the diagnosis of Epstein-Barr virus (EBV)
      infection still differentiate poorly between primary infection and reactivation.
      This is particularly true when IgG and IgM antibodies are present simultaneously
      and only a single serum sample is provided for analysis. The demonstration of the
      IgG avidity state has the potential to distinguish recent from past or
      reactivated infection. An analysis of the kinetics of avidity maturation of anti
      VCA antibodies in primary EBV infection was undertaken with longitudinally
      collected sets of sera from 28 well-characterised EBV cases and in sera from 35
      cases with previous EBV infection and recent primary infection due to HIV, CMV,
      or hepatitis A. Antibodies directed against the viral capsid antigen (VCA) and
      Epstein-Barr nuclear antigen (EBNA-1) were sought, using a commercial enzyme
      immunoassay (EIA). In parallel with standard IgG anti-VCA detection, serum was
      incubated with 8 M urea to disrupt low-avidity complexes to allow calculation of
      the percentage avidity. In cases with primary EBV infection, the mean avidity
      rose from 54% at 6 weeks to 82% by 28 weeks after the onset of symptoms, but
      remained lower than that of the control sera (96%). The addition of the avidity
      measurement improved the sensitivity of IgG and IgM anti-VCA testing in diagnosis
      of primary EBV infection from 93% to 100%. The specificity of IgM anti-VCA
      testing alone was poor, with 14 of 35 cases (49%) demonstrating false-positive
      results, but it improved to 97% by the demonstration of high-avidity IgG anti
      VCA. The combination of negative IgG anti-EBNA and low-avidity IgG anti-VCA had a
      sensitivity and specificity of 100%. The routine addition of IgG anti-VCA avidity
      estimation to diagnostic EBV serology is recommended.

PMID- 12794727
TI  - Latent and lytic HHV-8 mRNA expression in PBMCs and Kaposi's sarcoma skin
      biopsies of AIDS Kaposi's sarcoma patients.
AB  - Human herpes virus 8 (HHV-8) is associated with all clinical forms of Kaposi's
      sarcoma. HHV-8 DNA is present in Kaposi's sarcoma biopsies and is observed
      regularly in saliva and less consistently in blood of Kaposi's sarcoma patients.
      The expression pattern of latent (ORF 73) and lytic (vGCR, vBcl-2, and vIL-6) HHV
      8 mRNA was studied in peripheral blood mononuclear cell (PBMC) samples and
      Kaposi's sarcoma skin biopsies from 11 AIDS Kaposi's sarcoma patients with four
      different nucleic acid sequence-based amplification (NASBA) assays. Patients were
      divided into groups according to the clinical stage of Kaposi's sarcoma (stage I
      IV). All biopsies were positive for two or more of the mRNA measured. No clear
      difference could be seen in the expression pattern in the lesions of the
      different clinical stages. In the corresponding PBMC samples, very little or no
      mRNA was measurable in the patients with Kaposi's sarcoma stage I or II, whereas
      patients with more advanced Kaposi's sarcoma (stage III or IV) had more
      detectable mRNA in the PBMCs. Thus, the HHV-8 DNA load in the PBMCs increases in
      more advanced Kaposi's sarcoma, as does the frequency of mRNA detection in PBMCs.

PMID- 12794728
TI  - Congenital infection with human herpesvirus 6 variant B associated with neonatal
      seizures and poor neurological outcome.
AB  - Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The
      virus has been found in the cerebrospinal fluid of many children with aseptic
      meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA
      detection in cord blood specimens of apparently healthy newborns and in fetuses
      following spontaneous abortions. A patient is described with early neonatal
      afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed
      by repeated detection of viral genome by polymerase chain reaction (PCR) in
      cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance
      imaging (MRI) studies disclosed hyperintensities in the periventricular white
      matter and basal ganglia, associated with cerebral atrophy. Further follow-up at
      18 months revealed poor neurological outcome with mild neurodevelopmental
      retardation, strabismus and hypertonia of legs. This report provides evidence of
      neurological involvement after HHV 6 vertical transmission, and the association
      with neurological sequelae.

PMID- 12794729
TI  - Enhanced mucosal and systemic immune responses following intravaginal
      immunization with human papillomavirus 16 L1 virus-like particle vaccine in
      thermosensitive mucoadhesive delivery systems.
AB  - To develop more potent and convenient mucosal human papillomavirus (HPV)
      vaccines, we tested the effect of thermosensitive mucoadhesive vaginal vaccine
      delivery systems on the local and systemic antibody responses to HPV 16 L1 virus
      like particles (VLP). HPV 16 L1 VLP expressed from recombinant baculovirus
      infected Sf21 insect cells were delivered in phosphate-buffered saline (PBS) or
      thermosensitive mucoadhesive delivery systems, composed of poloxamers (Pol) and
      varying amounts of polyethylene oxide (PEO). Pol/PEO-based vaginal vaccine
      delivery systems existed in liquid form at room temperature, but gelled at 37
      degrees C. The mucoadhesiveness of Pol/PEO-based delivery systems increased with
      PEO, but the formulations with PEO higher than 1.0% were too viscous to be
      administered into the vagina. Vaccine vehicles affected the vaginal and salivary
      immune responses to HPV 16 L1 VLP intravaginally administered into mice. At 42
      days after the first intravaginal immunization of HPV 16 L1 VLP with cholera
      toxin, vaginal and salivary IgA titers were the highest in the group given in
      Pol/PEO 1.0% vehicle followed by Pol/PEO 0.4% and PBS vehicles. Intravaginal
      coadministration of HPV 16 L1 VLP and cholera toxin in Pol/PEO 1.0% showed 31-
      and 39-fold higher titers compared to the PBS-based HPV 16 L1 VLP groups
      administered by intravaginal and intramuscular routes, respectively. Following
      intravaginal administration, Pol/PEO 1.0%, but not Pol/PEO 0.4%, showed
      significantly higher HPV 16 L1 VLP-specific serum IgG titers as compared to the
      PBS vehicle. Our results indicate that the use of in situ-gelling vaginal vaccine
      delivery systems with increased mucoadhesiveness would be beneficial for more
      effective induction of mucosal and systemic immune responses to intravaginally
      administered HPV 16 L1 VLP vaccines.

PMID- 12794731
TI  - Genetic and antigenic characterization of measles viruses that circulated in
      Korea during the 2000-2001 epidemic.
AB  - Despite the marked reduction in the incidence of measles in Korea by the
      introduction of measles vaccine, a large measles epidemic occurred during 2000
      2001. During the epidemic, more than 55,000 measles cases were reported and at
      least 7 children were dead. In this study, we analyzed the genetic and antigenic
      properties of 15 measles viruses that isolated during the epidemic. Sequence
      analyses of entire hemagglutinin (H) and nucleoprotein (N) genes of the viruses
      indicated that all Korean isolates had a high degree of homology (>99.8%) when
      compared with each other. They differed from other wild-type viruses by as much
      as 6.8% in the H gene and 6.5% in the N gene at the nucleotide level. The deduced
      amino acid variability was up to 6.4% for the H protein and up to 6.5% for the N
      protein. Phylogenetic analysis of nucleotide sequences and deduced amino acid
      sequences of the H and N genes revealed that all Korean viruses were grouped into
      the genotype H1. This strongly demonstrated that single genotype of measles virus
      has been circulated in Korea during the 2000-2001 epidemic. Plaque reduction
      neutralizing antibody titers against vaccine strains, Edmonston and Schwarz, and
      recently isolated Korean strains were measured using sera from vaccinees and
      recently infected children. Although sera of recently infected children
      demonstrated higher neutralizing antibody titers against wild-type strains than
      against vaccine strains, both sera neutralized both strains and the reciprocal
      geometric mean titers (GMTs) were not significantly different against both
      strains.

PMID- 12794730
TI  - H1 genotype of measles virus was detected in outbreaks in Japan after 2000.
AB  - We investigated the molecular epidemiology and biological characteristics of wild
      measles viruses isolated since 1984 in Japan. The circulating measles virus was
      of genotype C1 before 1985, D3 from 1987 to 1990, and D5 from 1990 to 1997. It
      was replaced by the same cluster of Chicago-type D3 strain from 1997 to 1999. In
      2000, D5 recirculated with sporadic cases caused by genotype H1. The H1 genotype
      became dominant in 2001 with a minor distribution of D5. No significant
      difference was observed in neutralizing titers against C1, D3, D5, and H1 when we
      used sera having high neutralizing titers. However, some D3 and H1 strains were
      not completely neutralized with low levels of neutralizing antibody, and
      maintaining high levels of measles antibodies would be required for the control
      measles outbreaks.

PMID- 12794732
TI  - Role of neurosecretory cells in the photoperiodic induction of pupal diapause of
      the tobacco hornworm Manduca sexta.
AB  - In the tobacco hornworm, Manduca sexta, pupal diapause can be induced by exposure
      of fifth-instar larvae to a short-day photoperiod. We studied the effect of
      surgical ablation of tissues containing the neurosecretory cells of the brain of
      fifth-instar larvae on the photoperiodic induction of pupal diapause. At the end
      of the experiments, we immunostained the neurosecretory cells to determine the
      success of the ablations. Under long-day conditions (LD 16:8 at 22 degrees C),
      all intact larvae, most of the sham-operated larvae, and control-operated larvae
      developed into nondiapausing pupae. Under short-day conditions (LD 10:14 at 22
      degrees C), most intact, sham-operated, and control-operated larvae developed
      into diapausing pupae. Removal of type-II cells did not interfere with the
      photoperiodic response. Under long-day conditions, elimination of type-Ia(1)
      cells did not affect the incidence of nondiapausing pupae. When type-Ia(1) cells
      were removed under short-day conditions, however, the incidence of nondiapausing
      pupae was higher (51%, n = 41) than that of the intact (16%, n = 75), sham
      operated (24%, n = 88), control-operated larvae (5%, n = 40), and larvae with
      type-II cells removed (11%, n = 27). Thus, removal of type-Ia(1) cells can impede
      induction of diapause. These results indicate that the type-Ia(1) neurosecretory
      cells have an important role in the induction of pupal diapause.

PMID- 12794733
TI  - Expression of the immunoglobulin superfamily neuroplastin adhesion molecules in
      adult and developing mouse cerebellum and their localisation to parasagittal
      stripes.
AB  - Neuroplastin (np) 55 and 65 are immunoglobulin superfamily members that arise by
      alternative splicing of the same gene and have been implicated in long-term
      activity-dependent synaptic plasticity. Both biochemical and immunocytochemical
      data suggest that np55 is the predominant isoform (>95% of total neuroplastin) in
      cerebellum. Neuroplastin immunoreactivity is concentrated in the molecular layer
      and synaptic glomeruli in the granule cell layer. Expression in the molecular
      layer appears to be postsynaptic. First, neuroplastin is associated with Purkinje
      cell dendrites in two mouse granuloprival cerebellar mutants, disabled and
      cerebellar deficient folia. Second, in an acid sphingomyelinase knockout mouse
      with widespread protein trafficking defects, neuroplastin accumulates in the
      Purkinje cell somata. Finally, primary cerebellar cultures show neuroplastin
      expression in Purkinje cell dendrites and somata lacking normal histotypic
      organization and synaptic connections, and high-magnification views indicate a
      preferential association with dendritic spines. In the molecular layer,
      differences in neuroplastin expression levels present as a parasagittal array of
      stripes that alternates with that revealed by the expression of another
      compartmentation antigen, zebrin II/aldolase c. Neuroplastin immunoreactivity is
      first detected weakly at postnatal day 3 (P3) in the anterior lobe vermis. By P5,
      parasagittal stripes are already apparent in the immature molecular layer. At
      this stage, punctate deposits are also localised at the perimeter of the Purkinje
      cell perikarya; these are no longer detected by P15. The data suggest a role for
      neuroplastins in the development and maintenance of normal synaptic connections
      in the cerebellum.

PMID- 12794734
TI  - Trafficking of the muscarinic m2 autoreceptor in cholinergic basalocortical
      neurons in vivo: differential regulation of plasma membrane receptor availability
      and intraneuronal localization in acetylcholinesterase-deficient and -inhibited
      mice.
AB  - In vivo, the abundance of receptors at the neuronal plasma membrane may be
      critical in the mediation of pre- and postsynaptic responses. Thus, we have
      studied the membrane availability and intraneuronal distribution of the m2
      muscarinic autoreceptor (m2R) in cholinergic neurons of the nucleus basalis
      magnocellularis (NBM) projecting to the frontal cortex (FC). We have studied the
      subcellular compartmentalization of m2R at somatodendritic postsynaptic and
      axonal presynaptic sites in control animals (AChE +/+) and in two animal models:
      mice displaying acute acetylcholinesterase (AChE) inhibition by treatment with
      metrifonate, and AChE-deficient mice (AChE -/-). In control animals, m2R was
      mainly located at the plasma membrane in the somatodendritic field of NBM and in
      cortical varicosities. Acute AChE inhibition and chronic AChE deficiency induced
      a dramatic decrease of cell surface m2R in the somatodendritic compartment. This
      finding was associated with two different intracytoplasmic events: (1).
      internalization of m2R in endosomes after acute AChE inhibition, (2). exaggerated
      storage of m2R in the endoplasmic reticulum and Golgi complex in AChE -/- mice.
      In contrast, the m2R density was higher at the membrane of cortical varicosities
      in AChE -/- mice but unchanged in acutely AChE-inhibited mice. Our data
      demonstrate that acute and chronic stimulation provoke, in vivo, depletion of the
      membrane store of somatodendritic m2R through different intracellular mechanisms:
      endocytosis of receptors from the plasma membrane to the cytoplasm (acute) or
      regulation of their delivery from intracytoplasmic stores to the plasma membrane
      (chronic). The increase of m2R at the membrane of axonal varicosities after
      chronic stimulation suggest modulation of presynaptic cholinergic activity,
      including neurotransmitter release.

PMID- 12794735
TI  - Regeneration of myenteric plexus in the mouse colon after experimental
      denervation with benzalkonium chloride.
AB  - Recent reports suggest a far greater plasticity in nerve tissue than previously
      believed. As the digestive tract is exposed to a variety of insults, this
      question is relevant to enteric nerves, but little is known about their ability
      to recover from damage. To address this problem, we ablated the myenteric plexus
      of the mouse colon with the detergent benzalkonium chloride (BAC) and followed
      the ensuing morphologic changes for up to 60 days by using light- and electron
      microscopy. We found that, 2 days after BAC application, the treated area was
      essentially devoid of intact nerve elements. From day 7, new nerve fibers were
      observed within the denervated region. This growth progressed until, at days 30
      60, newly grown nerve fibers were present in most of this region, and the pattern
      of muscle innervation was similar to the normal one. At least part of these
      fibers originated at neurons within intact ganglia surrounding the denervated
      region. The cross-sectional area of neurons near the denervated region at day 14
      was 52% greater than controls. Glial cells were closely associated with the
      regenerating nerve fibers. From day 14 onward, we observed undifferentiated cells
      and differentiating neurons in ganglia surrounding the denervated region, and by
      day 30, new neurons were present in the myenteric region, along with regenerating
      nerve fibers. We conclude that the myenteric plexus is endowed with a
      considerable ability of regeneration and plasticity. The results provide evidence
      for the presence of stem cells and for an adult neurogenesis in this plexus.

PMID- 12794736
TI  - Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord
      injury.
AB  - Spinal cord injury (SCI) results in loss of voluntary motor control followed by
      incomplete recovery, which is partly mediated by the descending corticospinal
      tract (CST). This system is an important target for therapeutic repair strategies
      after SCI; however, the question of whether apoptotic cell death occurs in these
      axotomized neurons remains unanswered. In this study, adult (150-175 g) male
      Sprague-Dawley rats underwent T9 transection of the dorsal funiculus, which
      axotomizes the dorsal CST, and introduction of the retrograde tracer Fluoro-Gold
      into the lesion site. Primary motor cortex (M1) was then examined for evidence of
      apoptosis weekly for 4 weeks after injury. Axotomized pyramidal cells, identified
      by retrograde transport of Fluoro-Gold, were found in M1 (57.5 +/- 9.6/median
      section, 6127 +/- 292 total), and a significant proportion were terminal
      deoxynucleotidyl transferase (TdT) -mediated deoxyuridine triphosphate (dUTP)
      rhodamine nick end labeling (TUNEL) -positive at 1 week after injury (39.3 +/-
      5.6%), compared with animals undergoing sham surgery (1.2 +/- 1.4%). At 2-4
      weeks, fewer cells were Fluoro-Gold-positive (24.6 +/- 65.06 to 25.3 +/-
      6.4/median section, 2338 +/- 233 to 2393 +/- 124 total), of which very few were
      TUNEL-positive. In TUNEL-positive cells, Hoechst 33342 staining revealed nuclear
      morphology consistent with apoptosis, chromatin condensation, and formation of
      apoptotic bodies. Fluoro-Gold-positive cells showed increased caspase-3 and Bax
      immunoreactivity. Hematoxylin and eosin staining revealed similar nuclear changes
      and dystrophic cells. Internucleosomal DNA fragmentation was detected by gel
      electrophoresis at the 1-week time point. Lesioned animals not receiving Fluoro
      Gold exhibited the same markers of apoptosis. These results document, for the
      first time, features of apoptotic cell death in a proportion of axotomized
      cortical motor neurons after SCI, suggesting that protection from apoptosis may
      be a prerequisite for regenerative approaches to SCI.

PMID- 12794737
TI  - Brain nitric oxide synthase expression in the developing ferret lateral
      geniculate nucleus: analysis of time course, localization, and synaptic contacts.
AB  - Nitric oxide (NO) is a diffusible neurotransmitter that has been implicated in
      key developmental events, including the refinement of retinogeniculate axons into
      ON/OFF sublayers in the ferret lateral geniculate nucleus (LGN), and in the
      formation of eye-specific laminae in other species. To understand the role of NO
      in the LGN, it is critical to fully characterize the pattern of brain nitric
      oxide synthase (bNOS) expression within the nucleus, including the phenotype of
      the neural elements that express it. We have examined the temporal and spatial
      pattern of bNOS expression in the ferret LGN during the first 6 weeks of
      postnatal development, and in the adult, by detecting bNOS with a monoclonal
      antibody as well as beta-nicotinamide adenine dinucleotide phosphate-diaphorase
      histochemistry. We have found that bNOS is expressed in neurons in the A laminae
      of the LGN as early as postnatal day 7 (P7), a time coincident with eye-specific
      segregation of retinal axons. This expression continues through P35, with peak
      somatodendritic expression at P21. Fluorescent double labeling using antibodies
      to bNOS and glutamic acid decarboxylase indicate that bNOS is expressed in gamma
      aminobutyric acid-ergic interneurons within the A laminae. Electron microscopic
      examination of bNOS-labeled cells showed synaptic contacts from terminals with
      two distinct morphologic profiles. Expression of bNOS within interneurons that
      receive contacts from multiple sources indicates that the synaptic circuitry
      associated with bNOS activation and the potential targets of NO may be more
      complex than originally thought and supports a potential new role for
      interneurons as cellular intermediaries in the refinement of pathways in the LGN.
      Our findings broaden the window of time that bNOS may be active within the
      developing LGN, suggesting an expanded role for NO during early postnatal
      development.

PMID- 12794738
TI  - In aging, is it gray or white?

PMID- 12794739
TI  - Marked loss of myelinated nerve fibers in the human brain with age.
AB  - The white matter is the structure of the brain that declines most with age-almost
      30%, but little is known about the age-effect on the fibers that constitute the
      white matter. In the present study, the total length of myelinated fibers was
      measured with a newly developed stereologic method. Specimens came from 36 normal
      Danes (18 males and 18 females) with an age ranging between 18 and 93 years.
      Samples were taken systematically and randomly from the white matter, and the
      biopsy specimens were randomly rotated before sectioning to avoid bias due to the
      anisotropic nature of nerve fibers. The fibers were counted at light microscopic
      level at approximately 10,000x magnification, and the diameter of each counted
      fiber was measured to get the diameter distribution. Males were found to have a
      total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the
      age of 80, whereas the total length in females was 149,000 km at the age of 20
      and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per
      decade or a total decrease of 45% from the age of 20 to 80 years, and a sex
      difference of 16%. The fiber diameter distribution showed that primarily the
      thinner fibers were lost with a relative preservation of the thicker ones. The
      marked loss of myelinated nerve fibers with age could explain some of the
      cognitive decline seen in the elderly.

PMID- 12794740
TI  - Differential distribution of calbindin D28k and parvalbumin among functionally
      distinctive sets of structures in the macaque brainstem.
AB  - In a study of brainstem in the cynomolgus monkey, we found that the distribution
      of calbindin D28K (CB) and parvalbumin (PV) is nonoverlapping among functionally
      distinct sets of brainstem structures. Nuclei involved in representation and
      regulation of the organism's internal state contain CB, whereas those involved in
      the representation of the external environment and the representation or
      execution of externally directed actions contain only PV. Moreover, our findings
      indicate that different nuclei known as components of the ascending reticular
      activating system (ARAS) contain either CB or PV or both, suggesting that this
      system in primates operates with both CB and PV. In line with previously reported
      findings, we also found that unmyelinated pathways contain only CB, whereas
      myelinated pathways contain PV. Distribution of CB and PV in the macaque
      brainstem follows a pattern comparable to, but in some instances significantly
      different than, the pattern previously reported in the rat. We argue that the
      nonoverlapping distribution of CB and PV among different structures of the
      brainstem might reflect underlying differences in the physiological, anatomic,
      and perhaps phylogenetic properties of these structures. Considering our recent
      findings of selective vulnerability of brainstem structures to Alzheimer's
      disease, the present data suggest that the majority of macaque brainstem nuclei
      that contain CB are vulnerable to neurofibrillary tangles in humans. By contrast,
      only few nuclei that contain PV exhibit pathologic changes. Some of these nuclei
      are affected with a high number of neuritic plaques without ever developing
      neurofibrillary tangles.

PMID- 12794741
TI  - Parasol cells of the hemiellipsoid body in the crayfish Procambarus clarkii:
      dendritic branching patterns and functional implications.
AB  - Multimodal, higher-order sensory integration in decapod crustaceans occurs in
      local interneurons (parasol cells) within a structure in the lateral
      protocerebrum, the hemiellipsoid body, which is located dorsal to the terminal
      medulla. The hemiellipsoid body is targeted by projection neuron inputs by means
      of the olfactory globular tract from bilateral deutocerebral neuropils, the
      accessory lobes, which receive secondary visual, mechanosensory, and olfactory
      inputs. Parasol cell dendrites arborize extensively within the two neuropils of
      the hemiellipsoid body and possibly have some neurites within another neuropil at
      its base. The two neuropils of the hemiellipsoid body, neuropils I and II, are
      known to receive asymmetrical inputs from the contralateral and ipsilateral
      accessory lobes, and our current study addresses the question of the distribution
      of parasol cells within these two neuropils. Three anatomic methods were used to
      analyze this distribution: intracellular filling of cells with neurobiotin and
      visualization of the cells by using either a fluorescent or a peroxidase avidin
      conjugate, or placement of a fluorescent lipophilic tracer within a lobe of the
      hemiellipsoid body. All of these methods demonstrated that single parasol cells
      exclusively arborize within one of the two lobes of the hemiellipsoid body, but
      not in both lobes. Electrophysiological recordings from pairs of parasol cells
      with dendrites in the same or different lobes confirm a functional separation
      between neuropils I and II. Comparisons are made between insect and crustacean
      systems, emphasizing the inputs to the hemiellipsoid body and the mushroom body
      and similarities between extrinsic cells in insects and parasol cells in decapod
      crustaceans.

PMID- 12794742
TI  - Distribution of aromatase mRNA and protein in the brain and pituitary of female
      rainbow trout: Comparison with estrogen receptor alpha.
AB  - Recent data indicate that estrogens locally produced in the brain by
      aromatization of androgens could be important for neurogenesis and brain repair.
      In this respect, fish are interesting because of the extremely high aromatase
      activity of their brain. In this study, the rainbow trout brain aromatase was
      cloned and riboprobes were used to map the distribution of cells expressing the
      corresponding mRNAs. A very strong hybridization signal was detected in the
      pituitary and in cells bordering the ventricles in the telencephalon and ventral
      diencephalon, with the highest expression in the preoptic area and hypothalamus.
      A weaker signal was detected in the ependymal layer bordering the torus
      semicircularis and optic tectum. This localization was fully confirmed by
      immunohistochemistry using antibodies against a teleost aromatase. In addition,
      this antibody showed that aromatase expression in fact corresponds to radial
      glial cells because immunoreactive cells had long cytoplasmic processes extending
      toward the pial surface. Because brain aromatase was shown to be upregulated by
      estradiol in fish, the distribution of aromatase mRNAs was compared with that of
      rainbow trout estrogen receptor alpha (rtERalpha) on adjacent sections. Although
      the highest aromatase expression was found in regions expressing rtERalpha, no
      obvious coexpression was found, as rtERalpha was never observed in radial cells.
      However, reverse transcriptase-polymerase chain reaction experiments performed on
      brain cell cultures enriched in glial cells suggest that a weak expression of
      rtERalpha in glial cells cannot be excluded. The possible role of the high brain
      aromatase content in fish could be related to the continuous growth of their
      central nervous system during adulthood.

PMID- 12794743
TI  - Fiber connections of the torus longitudinalis and optic tectum in holocentrid
      teleosts.
AB  - Fiber connections of the torus longitudinalis (TL) and target(s) of toral
      recipient tectal neurons (pyramidal cells) in the optic tectum were examined by
      tract-tracing methods in holocentrids. Injections into the stratum marginale (SM)
      labeled neurons in the stratum opticum and stratum fibrosum et griseum
      superficiale (SFGS). They had superficial spiny dendrites, with a fan-shaped
      branching pattern in SM and a thick basal dendrite that gave rise to bushy
      horizontal branches at the boundary between the SFGS and the stratum griseum
      centrale (SGC), where an axon and a thin dendrite arose. The axon terminated in a
      middle cellular layer of the SGC, and the thin dendrite ramified slightly deeper
      to this cellular layer. The SM injections also labeled cells in the ipsilateral
      TL. Injections into either the lateral or the medial part of TL labeled terminals
      in the ipsilateral SM and neurons in the bilateral nucleus paracommissuralis
      (NPC) and nucleus subvalvularis and ipsilateral nucleus subeminentialis. Only
      medial TL injections labeled cells in the ipsilateral SGC. These neurons had a
      basal dendrite that branched in the middle cellular layer of SGC, suggesting that
      they receive inputs from the pyramidal cells and project back to the TL to form a
      closed circuit. Only lateral TL injections labeled terminals in the corpus
      cerebelli. A visual telencephalic portion projects to the NPC and sublayers of
      SGC, where dendrites of the pyramidal cells and SGC neurons ramify. The present
      results therefore suggest that the TL and SM are components of an intricate
      circuitry that exerts telencephalic descending visual influence on the optic
      tectum and corpus cerebelli.

PMID- 12794744
TI  - Distribution of glutamate-gated chloride channel subunits in the parasitic
      nematode Haemonchus contortus.
AB  - Glutamate-gated chloride channels (GluCl) are related to gamma-aminobutyric acid
      A (GABA(A)) receptors and are the target sites for the avermectin/milbemycin
      (A/M) anthelmintics, drugs that cause paralysis of the somatic and pharyngeal
      muscles in nematodes. We have previously identified four GluCl subunits,
      HcGluClalpha, HcGluClbeta, HcGluClalpha3A, and HcGluClalpha3B from the sheep
      parasite Haemonchus contortus. We raised specific antisera against all of these
      subunits and used them in immunofluorescence experiments on adult parasites. All
      of the subunits were expressed in the motor nervous system, especially motor
      neuron commissures. Double-immunostaining experiments suggested that HcGluClalpha
      and HcGluClbeta were expressed on the same commissures; these were also stained
      with an anti-GABA antibody, suggesting that they may be inhibitory motor neurons.
      The HcGluClbeta subunit was also detected in lateral and sublateral nerve cords.
      The HcGluClalpha3A and -B subunits, products of an alternatively spliced gene,
      were expressed in different neurons. We found HcGluClalphaA in a pair of sensory,
      possibly amphid, neurons in the head, in addition to the motor neuron
      commissures. HcGluClalpha3B was detected in three cell bodies, probably of
      pharyngeal neurons, and to ventral and lateral cords. These results indicate that
      the GluCl are widely distributed in the H. contortus nervous system and suggest
      that they have critical roles controlling locomotion, pharyngeal function, and
      possibly sensory processing in parasitic nematodes. They also provide an
      explanation for the observed effects of the A/M anthelmintics.

PMID- 12794745
TI  - Rats and mice exhibit distinct inflammatory reactions after spinal cord injury.
AB  - Spinal contusion pathology in rats and mice is distinct. Cystic cavities form at
      the impact site in rats while a dense connective tissue matrix occupies the
      injury site in mice. Because inflammatory cells coordinate mechanisms of tissue
      injury and repair, we evaluated whether the unique anatomical presentation in
      spinally injured rats and mice is associated with a species-specific inflammatory
      response. Immunohistochemistry was used to compare the leukocytic infiltrate
      between rats and mice. Microglia/macrophage reactions were similar between
      species; however, the onset and magnitude of lymphocyte and dendritic cell (DC)
      infiltration were markedly different. In rats, T-cell numbers were highest
      between 3 and 7 days postinjury and declined by 50% over the next 3 weeks. In
      mice, significant T-cell entry was not evident until 14 days postinjury, with T
      cell numbers doubling between 2 and 6 weeks. Dendritic cell influx paralleled T
      cell infiltration in rats but was absent in mouse spinal cord. De novo expression
      of major histocompatability class II molecules was increased in both species but
      to a greater extent in mice. Unique to mice were cells that resembled lymphocytes
      but did not express lymphocyte-specific markers. These cells extended from blood
      vessels within the fibrotic tissue matrix and expressed fibronectin, collagen I,
      CD11b, CD34, CD13, and CD45. This phenotype is characteristic of fibrocytes,
      specialized blood-borne cells involved in wound healing and immunity. Thus,
      species-specific neuroinflammation may contribute to the formation of distinct
      tissue environments at the site of spinal cord injury in mice and rats.

PMID- 12794746
TI  - Examination of the relationship between astrocyte morphology and laminar
      boundaries in the molecular layer of adult dentate gyrus.
AB  - Astrocytes are known to play an integral role in the development of compartmental
      boundaries in the brain and in the creation of trauma-induced boundaries.
      However, the physical relationship between astrocytes and such boundaries in the
      adult brain is less clear. If astrocytes do respect or play an ongoing role in
      maintaining such boundaries, a correlation between the position of such a
      boundary and the morphology of neighboring astrocytes might be observable. In
      this study, we examined the distribution of astrocytes with respect to the
      laminar boundaries compartmentalizing afferents to the dentate gyrus molecular
      layer. In addition, we attempted to determine whether astrocyte morphology is
      influenced by these laminar boundaries. To this end, protoplasmic astrocytes in
      the adult rat dentate gyrus were revealed with fluorescent tracer dyes and
      subsequently analyzed with respect to laminar boundaries demarcated by means of
      immunolabeling for the lamina-specific molecules EphA4 and neural cell adhesion
      molecule (N-CAM). We find that astrocyte distribution is influenced by the
      boundary separating the associational/commissural and perforant path afferents.
      In addition, we show that astrocytes in this region are polarized in their
      morphology, unlike typically stellate astrocytes, but that the laminar boundaries
      themselves do not appear to confer this morphology. This polarized morphology,
      however acquired, may have import for the functioning of astrocytes within the
      highly organized composition of the dentate gyrus molecular layer and for the
      overall microphysiology of this and other brain regions.

PMID- 12794747
TI  - Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels
      in neonatal GAP-43 heterozygous mice.
AB  - GAP-43 has been implicated in axonal pathfinding and sprouting, synaptic
      plasticity, and neurotransmitter release. However, its effect on cortical
      development in vivo is poorly understood. We have previously shown that GAP-43
      knockout (-/-) mice fail to develop whisker-related barrels or an ordered whisker
      map in the cortex. Here we used cytochrome oxidase (CO) histochemistry to
      demonstrate that GAP-43 heterozygous (+/-) mice develop larger than normal
      barrels at postnatal day 7 (P7), despite normal body and brain weight. Using
      serotonin transporter (5HT-T) histochemistry to label thalamocortical afferents
      (TCAs), we found no obvious abnormalities in other somatosensory areas or primary
      visual cortex of GAP-43 (+/-) mice. However, TCA projections to (+/-) primary
      auditory cortex were not as clearly defined. To clarify the mechanism underlying
      the large-barrel phenotype, we used lipophilic (DiI) axon labeling. We found
      evidence for multiple pathfinding abnormalities among GAP-43 (+/-) TCAs. These
      axons show increased fasciculation within the internal capsule, as well as
      abnormal turning and branching in the subcortical white matter. These pathfinding
      errors most likely reflect failures of signal recognition and/or transduction by
      ingrowing TCAs. In addition, many DiI-labeled (+/-) TCAs exhibit widespread,
      sparsely branched terminal arbors in layer IV, reflecting the large-barrel
      phenotype. They also resemble those found in rat barrel cortex deprived of
      whisker inputs from birth, suggesting a failure of activity-dependent
      synaptogenesis and/or synaptic stabilization in (+/-) cortex. Our findings
      suggest that reduced GAP-43 expression can alter the fine-tuning of a cortical
      map through a combination of pathfinding and synaptic plasticity mechanisms.

PMID- 12794748
TI  - Expression patterns of epidermal growth factor receptor and fibroblast growth
      factor receptor 1 mRNA in fetal human brain.
AB  - Factors that interact with the epidermal growth factor and fibroblast growth
      factor receptors have numerous effects in the central nervous system (CNS),
      inducing the proliferation of CNS stem cells and astrocytes and the survival and
      differentiation of neurons. Both receptors are expressed in the embryonic rodent
      brain in proliferative and nonproliferative regions, suggesting roles in numerous
      developmental processes. However, the roles of these factors in human brain
      development are not known. In the current study, we examined the expression of
      human epidermal growth factor receptor (HEGFR) and human fibroblast growth factor
      receptor 1 (HFGFR1) mRNAs in the human fetal brain. The expression of both
      receptors is strikingly conserved relative to previously reported patterns in the
      rodent. In the germinal zones, the sites of cellular proliferation, HFGFR1 was
      expressed primarily in the ventricular zone, whereas HEGFR was expressed in the
      subventricular zone, suggesting different roles in CNS progenitor proliferation.
      Differential expression was also observed in other brain areas examined,
      including the hippocampus and the cerebellum. The current study suggests that
      HEGFR and HFGFR1 are likely to play different roles during human brain
      development, but that these roles will be similar to those observed in the rodent
      brain.

PMID- 12794750
TI  - Mammary tumor latency is increased in mice lacking the inducible nitric oxide
      synthase.
AB  - Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and
      metastasis. Both stimulatory and inhibitory effects of NO have been reported in
      relation to breast cancer and its role in the development of malignancies and
      metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV
      mT) targeted to the mouse mammary gland and bred into an inducible NO synthase
      (iNOS)-deficient C57Bl/6 strain to examine a role for nitric oxide in modulating
      tumors that develop in the complex environment of the whole animal. The
      development of hyperplasias was delayed to the extent that the earliest palpable
      tumors arose 2-4 weeks later in PyV-mT/iNOS(-/-) mice compared with PyV
      mT/iNOS(+/+) mice, identifying a role for iNOS in early events in mammary tumor
      formation. Tumors that did develop in PyV-mT/iNOS(-/-) mice were
      characteristically well differentiated and had a cribriform pattern. Other tumors
      were myoepithelial adenocarcinomas with uniform nuclear size. In contrast, mice
      capable of iNOS activity typically developed solid nodular adenocarcinomas with a
      high mitotic index and pleomorphic nuclei. No significant effect of iNOS
      deficiency was found on vascular density in hyperplasias or tumors by examining
      CD31-positive vessels. The infiltration of lesions by macrophages, cells capable
      of significant NO production, remained unchanged in PyV-mT/iNOS(-/-) mice.
      Metastatic potential was retained by PyV-mT-transformed epithelium in the absence
      of iNOS, indicating that NO production by iNOS is not essential for this process.
      These results indicate a role for iNOS in tumorigenesis, particularly in the
      regulation of early events.

PMID- 12794751
TI  - Breast cell invasive potential relates to the myoepithelial phenotype.
AB  - On the basis of marker profile, the majority of breast carcinomas are thought to
      be derived from luminal epithelial cells; however, a subgroup of tumours with
      more mesenchymal characteristics are associated with a worse prognosis. The
      hypothesis of our study is that some breast carcinomas exhibit myoepithelial
      rather than pure mesenchymal differentiation and that acquisition of
      myoepithelial characteristics confers an aggressive phenotype. Pure luminal
      epithelial cells and fibroblasts are readily distinguished by many markers but
      distinguishing between myoepithelial and fibroblast cell lineages is more
      problematic. The markers found to be most discriminating in our study were CK14,
      alpha6beta4 integrin and the myoepithelial-associated desmosomal cadherin DSg3.
      These markers were applied to a series of breast cell lines and purified normal
      breast cell populations and the expression profile related to in vitro invasive
      behaviour. This demonstrated that expression of one or more myoepithelial markers
      by tumour cells (MDA MB 231, MDA MB 468, MDA MB 436) was associated with a high
      invasive capacity compared with cells with a pure luminal phenotype (MCF-7, T47D,
      ZR75). To address why myoepithelial characteristics are associated with higher
      invasion, the in vitro behaviour of normal myoepithelial cells and two other
      nontumourigenic breast cell lines (MCF-10A, HBL100) was also analysed. Primary
      myoepithelial cells from normal human breast exhibit a high invasive capacity
      when grown at low density, suggesting that invasive capacity is part of the
      myoepithelial phenotype. In keeping with this, both nontumourigenic cell lines
      exhibited features of the myoepithelial phenotype and a high invasive capacity.
      These results suggest that tumours that exhibit a myoepithelial phenotype may be
      clinically more aggressive because a high invasive capacity is intrinsic to the
      myoepithelial phenotype.

PMID- 12794752
TI  - Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas
      ligand in human pancreatic adenocarcinoma.
AB  - Many cancers are resistant to Fas-mediated apoptosis despite the expression of
      Fas. To investigate the mechanisms by which Fas signals are attenuated, we
      focused on decoy receptor 3 (DcR3). DcR3 is a soluble receptor against Fas ligand
      belonging to the tumor necrosis factor receptor superfamily and overexpresses in
      some forms of cancers. Exogenous DcR3 inhibits Fas-mediated apoptosis in Fas
      sensitive Jurkat cells. In our study, we examined the expression and function of
      DcR3 in pancreatic cancers. TaqMan RT-PCR showed that DcR3 mRNA was highly
      expressed in pancreatic cancer cell lines (71%) and tissues (67%). Its expression
      significantly correlated with cancer invasion to veins. Western blotting showed
      that the DcR3 protein was produced and secreted in 4 of 6 cell lines. The protein
      expressions were compatible with the mRNA expression. Five of 7 pancreatic cancer
      cell lines became sensitive to agonistic anti-Fas antibody (CH-11) to various
      extents, without Fas upregulation, when exposed to CH-11 for 48 hr after
      pretreatment with IFNgamma. Four of 7 pancreatic cancer cell lines were inhibited
      from growing, compared to control cells, when cocultured with membrane-bounded
      Fas ligand (mFasL) transfected lymphomas for 48 hr after pretreatment with
      IFNgamma. DcR3 reduced this growth inhibition when added exogenously. Regression
      analysis showed that the DcR3 expression significantly correlated with the
      sensitivity to mFasL, and not to CH-11. These results suggest that DcR3 is highly
      expressed in many pancreatic cancers and endogenous DcR3 blocks the growth
      inhibition signals mediated by mFasL. DcR3 can be a candidate target molecule for
      the therapeutic intervention.

PMID- 12794753
TI  - Signaling pathway for aloe-emodin-induced apoptosis in human H460 lung nonsmall
      carcinoma cell.
AB  - Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active
      component from the root and rhizome of Rheum palmatum that has been reported to
      exhibit antitumor effects through an unknown mechanism. Our study investigated
      the mechanisms of aloe-emodin-induced cell death in the human lung nonsmall cell
      carcinoma cell line H460. Aloe-emodin (40 microM)-induced apoptosis of H460 cells
      involves modulation of cAMP-dependent protein kinase, protein kinase C, Bcl-2,
      caspase-3 and p38 protein expression. The relationship of various signals
      involved in cell death, such as cAMP-dependent protein kinase, protein kinase C,
      Bcl-2, caspase-3 and p38, has been investigated in the regulation of apoptotic
      cell death of aloe-emodin. We demonstrated that the expression of p38 is an
      important determinant of apoptotic death induced by aloe-emodin.

PMID- 12794754
TI  - Expression profiles of angiogenic growth factors in squamous cell carcinomas of
      the head and neck.
AB  - Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has
      become a major target in experimental cancer therapies. This therapeutical
      approach requires a profound knowledge of growth factor profiles that contribute
      to tumor growth and progression. The respective knowledge is presently rather
      incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we
      studied expression of several angiogenic cytokines including VEGF, bFGF, PDGF-AB,
      PDGF-BB, G-CSF and GM-CSF in HNSCC in vivo and in vitro. In tumor tissues
      expression of all cytokines was observed albeit with marked differences
      concerning intensity and distribution pattern. Quantification of the cytokines in
      the supernatant of 15 tissue-corresponding HNSCC cultures revealed that VEGF,
      PDGF-AB and less frequently GM-CSF were secreted in high amounts of up to 13
      ng/ml/10(6) cells. Twenty percent of the HNSCC cultures expressed only 1 cytokine
      in biologically active amounts, 60% 2 or 3 and 20% expressed the maximum of 4
      cytokines simultaneously. Interestingly, we observed a distinct cytokine pattern:
      HNSCC cells secreting only 1 or 2 cytokines presented always with either VEGF
      and/or PDGF-AB, while G-CSF and GM-CSF were secreted primarily together with VEGF
      and PDGF-AB. The number of cytokines expressed by HNSCC cells correlated with the
      microvessel density of the original tumor and with the clinical outcome: tumors
      producing at least 3 cytokines revealed a significantly poorer patient prognosis.
      Our data indicate a major role for VEGF and PDGF-AB in HNSCC and that the
      additional secretion of G-CSF or GM-CSF might contribute to a poorer prognosis in
      patients suffering from these tumors.

PMID- 12794755
TI  - RASSF1A gene inactivation in non-small cell lung cancer and its clinical
      implication.
AB  - Methylation-associated inactivation of RASSF1, a putative tumor suppressor
      identified at 3p21.3, is reported in several cancers. We examined RASSF1 in non
      small lung cancer (NSCLC) to search for clinical implications. RT-PCR analysis
      showed no expression of RASSF1A in 12 of 20 lung cancer cell lines. Loss of
      expression correlated well with promoter methylation status of these lines.
      Sequence analysis revealed 2 polymorphisms (codons 21 and 133) in RASSF1A
      transcripts, but not in RASSF1C transcripts. No somatic mutations were found. Of
      7 cell lines with K-ras mutations at codon 12 or 61, 2 lost expression of
      RASSF1A, whereas in 13 cell lines with wild-type K-ras gene, 10 lost RASSF1A gene
      expression (p = 0.0521). We investigated methylation status of this putative
      tumor suppressor gene in 100 primary NSCLCs to determine whether there is a
      clinical significance. Forty-two of primary NSCLCs demonstrated methylated
      allele. There is no correlation between promoter methylation of RASSF1A and
      clinicopathological findings, including histological type or grade, tumor
      staging, p53 and K-ras mutational status, or patients' survival. In the cases of
      Stage I and II disease, however, RASSF1A methylation was associated with earlier
      recurrence (p = 0.0247). Epigenetic silencing of RASSF1A is a frequent event in
      non-small lung cancer and will provide novel opportunities to develop diagnosis
      and therapy of NSCLC.

PMID- 12794756
TI  - Distinct methylation profiles of glioma subtypes.
AB  - Gliomas are tumors of the central nervous system with a wide spectrum of
      different tumor types. They range from pilocytic astrocytoma, with a generally
      good prognosis, to the extremely aggressive malignant glioblastoma. In addition
      to these 2 types of contrasting neoplasms, several other subtypes can be
      distinguished, each characterized by specific phenotypic, as well as genotypic
      features. Recently, the epigenotype, as evident from differentially methylated
      DNA loci, has been proposed to be useful as a further criterion to distinguish
      between tumor types. In our study, we screened 139 tissue samples, including 33
      pilocytic astrocytomas, 46 astrocytomas of different grades, 7 oligoastrocytomas,
      10 oligodendrogliomas, 10 glioblastoma multiforme samples and 33 control tissues,
      for methylation at CpG islands of 15 different gene loci. We used the
      semiquantitative high throughput method MethyLight to analyze a gene panel
      comprising ARF, CDKN2B, RB1, APC, CDH1, ESR1, GSTP1, TGFBR2, THBS1, TIMP3, PTGS2,
      CTNNB1, CALCA, MYOD1 and HIC1. Seven of these loci showed tumor specific
      methylation changes. We found tissue as well as grade specific methylation
      profiles. Interestingly, pilocytic astrocytomas showed no evidence of CpG island
      hypermethylation, but were significantly hypomethylated, relative to control
      tissues, at MYOD1. Our results show that glioma subtypes have characteristic
      methylation profiles and, with the exception of pilocytic astrocytomas, show both
      locus specific hyper- as well as hypomethylation.

PMID- 12794757
TI  - Alterations of BLU, a candidate tumor suppressor gene on chromosome 3p21.3, in
      human nasopharyngeal carcinoma.
AB  - Nonrandom allelic loss on chromosome 3p is a common event in nasopharyngeal
      carcinoma (NPC) with the implication that certain tumor suppressor gene(s) in
      this region are involved in the pathogenesis of these tumors. The BLU gene,
      located at 3p21.3, has recently been identified as a candidate tumor suppressor
      gene due to the occurrence of missense mutations and loss of its expression in
      lung cancer. To investigate the involvement of BLU gene in NPC, we examined both
      genetic and epigenetic changes of BLU in NPC primary tumors and cell lines. No
      pathogenic mutations were detected in the entire coding region of this gene in 45
      primary NPC tumors and 5 NPC cell lines. While BLU was expressed in 100% (15 of
      15) of noncancerous nasopharyngeal epithelia, its transcripts were missing in all
      5 NPC cell lines, and absent or reduced mRNA levels were observed in 78% (28 of
      36) of the primary tumors. In the NPC cell lines, loss of BLU expression
      correlated with hypermethylation of the CpG island promoter sequence, and
      expression was restored after treatment with 5'-aza-2'-deoxycytidine. Methylation
      specific PCR analysis revealed that the BLU promoter was highly methylated in 74%
      (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9
      non-neoplastic nasopharyngeal epithelia exhibited hypermethylation in the BLU
      promoter region. The high incidence of BLU alterations suggests that it may be
      one of the critical tumor suppressor genes on chromosome 3p21.3 involved in the
      development of NPC.

PMID- 12794759
TI  - Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced
      breast carcinomas.
AB  - Allelic imbalance constitutes a major mechanism of genetic aberrations in breast
      cancer and strongly indicates the involvement of tumor associated genes in the
      affected chromosomal regions. Preliminary results from our study indicated the
      existence of a tumor suppressor gene located on chromosomal arm 15q which may be
      involved in breast cancer progression.1 In the present study, 210 primary breast
      carcinomas, 30 metastases and 26 local recurrences from primary breast carcinomas
      have been analyzed with a panel of 18 highly polymorphic microsatellite markers
      spanning the chromosomal region 15q11-21.3. Allelic imbalance at 15q with at
      least 1 marker was seen in 36 of 56 (64.3%) metastases and recurrences, but only
      in 58 of 210 (27.6%) primary tumors (p<0.0001). We identified a subregion defined
      by microsatellite marker CYP19 (15q21.1) that showed significantly higher
      frequencies of allelic imbalance in metastases and recurrences (57.6%) when
      compared to primary carcinomas (8.9%; p<0.0001). Allelic imbalance at 15q was
      correlated with histopathologic parameters of the patients with primary breast
      carcinomas. We detected a significant association with established predictors of
      poor prognosis, i.e., negative estrogen receptor status (p=0.003), negative
      progesterone receptor status (p=0.028), high grade (p=0.014) and positive
      axillary lymph nodes (p=0.013). In summary, our data provide further evidence for
      a novel prognostic marker in breast carcinomas located in the chromosomal region
      15q21.

PMID- 12794758
TI  - Role of hMLH1 promoter hypermethylation in drug resistance to 5-fluorouracil in
      colorectal cancer cell lines.
AB  - Loss of DNA mismatch repair (MMR) occurs in 10-15% of sporadic colorectal cancer,
      is usually caused by hMLH1 hypermethylation, and has been shown to confer
      resistance to various chemotherapeutic reagents, including 5-fluorouracil (5-FU).
      We tested the hypothesis that demethylation of the hMLH1 promoter in
      hypermethylated colorectal cancer cells would restore MMR proficiency and drug
      sensitivity to 5-FU. We used the MMR-deficient cell lines SW48, HCT116,
      HCT116+chr2 and the -proficient cell line HCT116+chr3. After treatment with the
      demethylating agent 5-Aza-2'-deoxycytidine (5 aza-dC), hMLH1 mRNA and protein
      expression were determined by RT-PCR and immunoblots. The methylation status for
      hMLH1 was investigated by methylation-specific PCR. Cells were subsequently
      treated with 5-FU and the growth characteristics ascertained by clonogenic
      assays. hMLH1 hypermethylation was reverted in SW48 cells 24 hr after treatment
      with 5 aza-dC and was accompanied by hMLH1 mRNA and protein reexpression. While 5
      aza-dC alone did not affect the growth of SW48 cells, all other cell lines
      responded with a pronounced growth inhibition. 5-FU treatment strongly reduced
      the colony formation of HCT116+chr3 cells. These effects were significantly less
      in the MMR-deficient cells. Combined treatment of SW48 cells resulted in a
      similar growth pattern as seen in 5-FU only treated HCT116+chr3 cells. We
      demonstrate that in vitro resistance to 5-FU can be overcome by reexpression of
      hMLH1 protein through 5 aza-dC-induced demethylation in hypermethylated cell
      lines. Induction of the expression of methylated tumor suppressor or MMR genes
      could have a significant impact on the development of future chemotherapy
      strategies.

PMID- 12794760
TI  - Exclusion of BRAFV599E as a melanoma susceptibility mutation.
AB  - Very recently, BRAF mutations were found in about 2/3 of malignant melanomas and
      at lower frequencies in other human cancers. The BRAF gene codes for a protein in
      the mitogen-activated protein kinase (MAPK) pathway. All mutations identified to
      date are within the kinase domain, with a single missense mutation (V599E)
      accounting for 80%. We investigated the hypothesis that this common somatic BRAF
      mutation (V599E) would contribute to melanoma predisposition in familial and
      polygenic malignant melanoma if occurring as a germ-line mutation. We performed
      comprehensive mutational screening of exon 15 of BRAF using DHPLC (denaturing
      high-performance liquid chromatography) and DNA sequencing techniques. No V599E
      mutation could be detected in 172 melanoma patients comprising 46 familial cases,
      21 multiple melanoma patients and 106 cases with at least one first-degree
      relative suffering from other cancers. We therefore conclude that the common
      somatic BRAF mutation V599E does not contribute to polygenic and familial
      melanoma predisposition.

PMID- 12794761
TI  - CD1d-mediated stimulation of natural killer T cells selectively activates hepatic
      natural killer cells to eliminate experimentally disseminated hepatoma cells in
      murine liver.
AB  - Since hepatocellular carcinomas (HCCs) develop from transformed hepatocytes,
      sometimes in a multicentrical manner, immunological deletion of such small
      intrahepatic regions should be an important strategy to prevent HCC development.
      The liver contains abundant innate cell lineages including natural killer (NK)
      cells and natural killer T (NKT) cells, the latter of which become activated in a
      CD1d-restricted manner by alpha-galactosylceramide (alpha-GalCer). In our study,
      we investigated the anti-tumor effect elicited by alpha-GalCer administration
      against transplanted hepatoma cells in the liver, in comparison with that in
      extrahepatic sites. alpha-GalCer administration completely suppressed the growth
      of BNL 1MEA.7R.1 (BNL) hepatoma cells disseminated in the liver of syngeneic
      BALB/c mouse but had no anti-tumor effect on subcutaneously implanted BNL cells.
      Hepatic NKT cells became rapidly activated after alpha-GalCer administration
      compared to splenic NKT cells and then disappeared. Hepatic NK cells
      substantially increased their population as well as up-regulated their cytotoxic
      activity against BNL cells, but NK cells in other tissues, including the spleen,
      blood and lymph node, did not. Anti-asialo GM1 antibody treatment, which depleted
      NK cells in vivo, resulted in hepatic tumor formation in alpha-GalCer-treated
      mice, indicating the critical involvement of NK cells in the alpha-GalCer-induced
      anti-tumor effect in the liver. In conclusion, our study demonstrates clear
      differences in NK cell activation and anti-tumor effect through stimulation of
      NKT cells by alpha-GalCer between the liver and extrahepatic tissues. Sequential
      activation of these innate cell lineages may be an attractive strategy for
      controlling micro-disseminated hepatoma cells in the liver.

PMID- 12794762
TI  - Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, 
      3, C-peptide and risk of postmenopausal breast cancer.
AB  - Higher levels of circulating Insulin-like Growth Factor (IGF)-I may be associated
      with higher risks for premenopausal breast cancer. We investigate the
      associations between circulating levels of IGF-I, its binding proteins (IGFBPs) 
      1, -2, -3, C-peptide and postmenopausal breast cancer. This is a prospective
      study nested in 2 Dutch cohorts. The study population included women who were
      postmenopausal at baseline. Breast cancer cases were identified through linkage
      with cancer registries. Controls were matched to cases by cohort, age, date of
      blood donation and place of residence. In total, 149 breast cancer cases and 333
      healthy controls were included. Plasma levels of IGF-I, IGFBP-1, -2, -3 and C
      peptide were measured by radioimmunoassays. Estimates of the relative risk for
      breast cancer associated with the quartiles of the peptides' circulating levels
      were obtained by conditional logistic regression. Models were adjusted for BMI,
      age at menarche and age at first full-term delivery. For IGF-I, the adjusted OR
      (95% CI) of the top vs. bottom quartile was 1.1 (0.6; 2.1); for IGFBP-1 it was
      0.7 (0.3; 1.3); for IGFBP-2, 1.1 (0.5; 2.4); for IGFBP-3, 1.6 (0.7; 3.5), for C
      peptide, 1.3 (0.7; 2.7) and for IGF-I/IGFBP-3 ratio, 1.0 (0.5; 1.8). Our data do
      not support an association between postmenopausal circulating levels of IGF-I,
      IGFBP-1, -2, -3, C-peptide and postmenopausal breast cancer.

PMID- 12794763
TI  - Effect of family history, obesity and exercise on breast cancer risk among
      postmenopausal women.
AB  - We examined effects of obesity and lifetime exercise patterns on postmenopausal
      breast cancer risk according to family history in a large population-based case
      control study conducted in Los Angeles County, California, because we
      hypothesized that both factors would affect risk through similar mechanistic
      pathways, and that their effects would be stronger among women with a family
      history. We studied 1883 postmenopausal breast cancer case subjects and 1628
      postmenopausal control subjects ranging in age from 55-72 years. Cases were
      diagnosed with incident breast cancer in the late 1980s and 1990s. Controls were
      individually matched to case subjects on age, ethnic origin and neighborhood. In
      person interviews determined known breast cancer risk factors including: height,
      weight, lifetime exercise, and family history of breast and other cancers. Breast
      cancer risk was raised among women who had at least 1 first-degree relative with
      breast cancer (odds ratio [OR] = 1.68; 95% confidence interval [CI] = 1.36-2.08).
      Risk increased with increasing levels of body-mass index (wt-kg/ht-m(2)) (p-trend
      = 0.005). Breast cancer risk was reduced among women who maintained, on average,
      17.6 metabolic equivalent of energy expenditure (MET)-hr of activity/week from
      menarche onward (OR = 0.66; 95% CI = 0.48-0.90). Body-mass index, adjusted for
      lifetime exercise, was strongly associated with breast cancer risk among women
      with a positive family history of breast cancer (p-trend < 0.0001), but only
      weakly associated among women with no family history (p-trend = 0.08; homogeneity
      of trends p = 0.0005). In contrast, the risk reduction associated with exercise
      activity, adjusting for body-mass index, was limited to women without a family
      history of breast cancer (p-trend = 0.001; homogeneity of trends p = 0.005). Body
      mass index and exercise activity, both modifiable risk factors for breast cancer,
      seem to have differential effects depending on a woman's family history of breast
      cancer, and may impact risk through different biological mechanisms.

PMID- 12794764
TI  - Prospective study of screening for stomach cancer in Japan.
AB  - Although screening for stomach cancer is a widespread community service in Japan,
      the benefits of the screening program remain unclear. Our study investigated
      prospectively the relation between participation in stomach-cancer screening
      during the past 12 months and subsequent deaths. Data was derived from the Japan
      Collaborative Cohort Study, in which 480 stomach-cancer deaths were identified
      during an 8-year follow-up period. Cox proportional hazard regression was used to
      estimate the relative risk of death from stomach cancer and that from other
      causes while adjusting for potential confounding factors. In men, screening
      participation was associated significantly with a reduced risk of death from
      stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41
      0.70). The extent of the risk reduction was greater than potential health
      selection (for deaths other than stomach, RR = 0.71). The adjustment for
      potential confounding variables, however, attenuated the difference in risk of
      death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the
      magnitude of the association between screening participation and death from
      stomach cancer (RR = 0.74; 95% CI = 0.52-1.07) was equal to that for deaths from
      non-stomach cancers (RR = 0.74). Subgroup analysis showed that women with a
      parental history of stomach cancer had a reduced risk of death from stomach
      cancer associated with screening (RR = 0.32; 95% CI = 0.12-0.87). The present
      results underline the potential for selection bias in observational studies, and
      thus it remains an open question whether screening for stomach cancer is
      effective.

PMID- 12794765
TI  - Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the
      anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells.
AB  - Salvicine, a novel topoisomerase II inhibitor and a diterpenoid quinone compound,
      exerts potent in vitro and in vivo antitumor effects. In our study, we show that
      salvicine effectively kills multidrug-resistant (MDR) sublines, such as K562/A02,
      KB/VCR and MCF-7/ADR, and parental K562, KB and MCF-7 cell lines to an equivalent
      degree. These cytotoxic activities of salvicine were much more potent than those
      of several classical anticancer drugs (average resistance factor: 1.42 for
      salvicine vs. 344.35, 233.19 and 71.22 for vincristine, doxorubicin and
      etoposide, respectively). Flow cytometry and DNA agarose gel electrophoresis
      demonstrated that salvicine induced similar levels of apoptosis in MDR K562/A02
      and parental cells. The compound activated caspase-1 and -3 (but not caspase-8)
      and increased the ratio of bax to bcl-2 mRNA via reduction of bcl-2 mRNA
      expression in the same cells. Furthermore, salvicine induced the downregulation
      of mdr-1 gene and P-gp expression but had no effect on MRP and LRP gene
      expression in MDR K562/A02 cells. These results suggest that the reduction of mdr
      1 and bcl-2 expression by salvicine possibly contributes to its cytotoxicity and
      apoptotic induction in this system. The effectiveness, broad-spectrum activity
      and possibly novel mechanism of killing MDR tumor cells in vitro of salvicine
      signify promising in vivo and clinical activity. The novel chemical structure of
      this compound further implies a role for salvicine in future MDR tumor therapy.

PMID- 12794766
TI  - Synergistic antiproliferative and apoptotic effects induced by epidermal growth
      factor receptor and protein kinase a inhibitors in human prostatic cancer cell
      lines.
AB  - Our results revealed that the blockade of epidermal growth factor receptor (EGFR)
      tyrosine kinase and protein kinase A (PKA) signaling pathways by specific
      inhibitors (PD153035 and Rp-cAMPs) leads to a synergistic inhibition of EGF- and
      serum-stimulated growth of human prostatic cancer cells (LNCaP, DU145 and PC3)
      concomitant with an arrest in the G1 phase of cellular cycle. Of particular
      interest, the combination of PD153035 and Rp-cAMPs also caused a more substantial
      apoptotic/necrotic death of these prostatic cancer cells as compared to drugs
      alone. Moreover, we observed that the inhibition of acidic sphingomyelinase and
      caspase cascades results in a marked reduction of DNA fragmentation and apoptotic
      death induced by PD153035, alone or in combination with Rp-cAMPs, in EGF
      stimulated PC3 cells. This suggests that these agents might mediate their
      cytotoxic effects at least in part via the ceramide generation and activation of
      caspase signaling pathways. N-oleoylethanolamine (OE), an inhibitor of acidic
      ceramidase, consistently potentiated the apoptotic effects of PD153035 in all the
      prostatic cancer cell lines tested. Additionally, the cellular ceramide content
      estimated for PC3 cells was increased after treatment with PD153035, alone or in
      combination, at a lower dose with OE and Rp-cAMPs. The synergistic apoptotic
      effect of PD153035 plus Rp-cAMPs induced in PC3 was also accompanied by a
      significant rate of mitochondrial membrane depolarization and release of
      cytochrome c into cytosol as compared to drugs alone. Combined, the results
      indicated that the simultaneous inhibition of EGFR and PKA signaling cascades
      might lead to a more massive apoptotic death of metastatic prostatic cancer cells
      by increasing ceramide accumulation and activating of caspase cascade of a
      mitochondrial dependent manner.

PMID- 12794767
TI  - In vitro and in vivo studies of the anticancer action of terbinafine in human
      cancer cell lines: G0/G1 p53-associated cell cycle arrest.
AB  - Terbinafine (TB) (Lamisil), a promising oral antifungal agent used worldwide, has
      been used in the treatment of superficial mycosis. In our study, we demonstrated
      that TB dose-dependently decreased cell number in various cultured human
      malignant cells. Flow cytometry analysis revealed that TB interrupts the cell
      cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer
      cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was
      inhibited just as the levels of p53, p21/Cip1 and p27/Kip1 proteins were
      augmented. In the TB-treated COLO 205, the binding between p53 protein and p53
      consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment
      of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB
      induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in
      the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB
      treatment did not induce cell cycle arrest. Taken together, these results suggest
      an involvement of the p53-associated signaling pathway in the TB-induced
      antiproliferation in COLO 205. We further examined whether administration of TB
      could affect the growth of tumors derived from human colon cancer cells in an in
      vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid
      tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious
      decline in tumor size, up to 50-60%. In these tumors, increases in the p21/Cip1,
      p27/Kip1 and p53 proteins and the occurrence of apoptosis were observed. Combined
      treatment with TB and nocodazole (ND), a clinically used anticancer agent,
      potentiated the apoptotic effect in COLO 205. These findings demonstrate for the
      first time that TB can inhibit the proliferation of tumor cells in vitro and in
      vivo.

PMID- 12794768
TI  - MMTV-related env sequences in human breast tumor.

PMID- 12794770
TI  - SV40 and human brain tumors.

PMID- 12794773
TI  - The development of phenotypic plasticity: where biology and psychology meet.

PMID- 12794774
TI  - The effects of isolation rearing on open-field behavior in male rats depends on
      developmental stages.
AB  - The effects of the duration of isolation and age during isolation on open-field
      behavior in rats were examined. An inner wall divided the floor of the field into
      two areas, a peripheral alley and the center square, and the subjects' behavior
      in each area was measured. An increase in the tendency to avoid the center square
      was found in rats isolated during their juvenile stage, which disappeared if they
      were reared in pairs for a long period after isolation. On the other hand,
      subjects isolated during their postmaturity stage displayed an increased tendency
      to approach the center square whereas isolation during sexual maturity had no
      effect. The duration of isolation showed no consistent effect; rather, the effect
      depended on the age of the subjects during isolation. These findings suggest that
      isolation affects the open-field behavior of rats in various ways, depending on
      their age during isolation.

PMID- 12794775
TI  - Environmental enrichment: effects on stereotyped behavior and dendritic
      morphology.
AB  - We evaluated whether environmental enrichment-related effects on the development
      of stereotyped behavior in deer mice were associated with alterations in
      dendritic morphology. Deer mice were reared under enriched or standard housing
      conditions and then tested in automated photocell detectors and classified as
      stereotypic or nonstereotypic. Dendritic morphology was assessed in layer V
      pyramidal neurons of the motor cortex, medium spiny neurons of the dorsolateral
      striatum, and granule cells of the dentate gyrus using Golgi-Cox histochemistry.
      Enriched nonstereotypic mice exhibited significantly higher dendritic spine
      densities in the motor cortex and the striatum than enriched stereotypic or
      standard-cage mice. Significant increases in dendritic arborization following
      environmental enrichment also were observed. These results suggest that the
      enrichment-related prevention of stereotyped behavior is associated with
      increased dendritic spine density.

PMID- 12794776
TI  - Effects of perinatal visual stimulation on preference, growth, and mortality in
      African clawed frogs (Xenopus Laevis).
AB  - Two exploratory experiments examined the effects of flashing light stimulation on
      growth, mortality, and behavioral preferences of Xenopus laevis tadpoles.
      Experiment 1 showed that tadpoles exposed to continuous visual stimulation, from
      egg-laying through postnatal day 40, had significantly higher mortality rates and
      weighed significantly less than controls. In contrast to controls, experimental
      tadpoles showed a preference for visual stimulation throughout early development.
      Results support the notion that augmented visual stimulation during early
      development affects species-typical development and the creation of postnatal
      preferences. Experiment 2 exposed subjects to propranolol in their water to
      investigate a potential sympathetic nervous system (SNS) mechanism responsible
      for the previous results. Tadpoles exposed to propranolol and visual stimulation
      simultaneously did not show a preference for the visual stimulation. Although
      this preliminary finding suggests SNS involvement, this notion deserves further
      investigation.

PMID- 12794777
TI  - Placentophagia in rabbits: incidence across the reproductive cycle.
AB  - Rabbits show placentophagia at parturition, but the regulation of this behavior
      and its incidence across the reproductive cycle are unknown. By testing estrous,
      midpregnant, prepartum (day 1), and postpartum (days 1 and 5) food-deprived
      rabbits with liver and placenta, we found an absence or infrequency (<%) of
      placentophagia in the former three groups, an invariable occurrence at
      parturition, and a persistence into postpartum days 1 and 5 (50 and 48%,
      respectively). Most placentophagic females also ate liver on postpartum day 1,
      but not on postpartum day 5. In different food-deprived rabbits, tested every 2
      hr with placenta and food pellets, placentophagia incidence was 20% at 8 hr
      prepartum, 100% at parturition, and 67 and 21% at 8 and 24 hr postpartum,
      respectively. Most placentophagic rabbits also ate food pellets in postpartum
      (but not in prepartum) tests. Results suggest that somatosensory, hormonal, or
      both factors of the peripartum period regulate placentophagia expression.

PMID- 12794778
TI  - Using a continuous index of laterality to determine how laterality is related to
      interhemispheric transfer and bimanual coordination in children.
AB  - We sought to determine whether laterality is related to interhemispheric transfer
      and bimanual coordination during development. Children between 3 and 8 years of
      age were observed. In the first part of the experiment, we devised a continuous
      index to order the subjects according to their laterality. The laterality index
      included evaluation of hand and eye preference, and the right-left performance
      difference. In the second part of the experiment, we used this single index to
      determine whether laterality is related to interhemispheric transfer and bimanual
      coordination. Interhemispheric transfer was assessed by means of two tactile
      transfer tasks and one visuo-manual transfer task. We assessed bimanual
      coordination using the tapping task and the bimanual crank-rotation task. Results
      showed that right- and left-hand writers overlap on certain measures of
      laterality. They confirmed the improvement of interhemispheric transfer at around
      age 5 years, earlier progress in bimanual coordination with mirror than with
      parallel movements, and the existence of a relationship between visuo-manual
      interhemispheric transfer and bimanual coordination. The laterality index was not
      related to interhemispheric transfer, but it was related to the younger subjects'
      performance on the bimanual crank-rotation task: the less right handed, the
      better the bimanual coordination. In addition, on the same bimanual task, crossed
      hand-eye laterality was associated with better performance.

PMID- 12794779
TI  - Spontaneously hypertensive and Wistar Kyoto rats differ in delayed matching-to
      place performance and response to dietary long-chain polyunsaturated fatty acids.
AB  - Spontaneously hypertensive rats (SHR) were used as an animal model of attention
      deficit hyperactivity disorder (ADHD). This study investigated whether, in
      comparison with its progenitor strain, Wistar-Kyoto rats (WKY), SHR would show
      deficits in spatial short-term memory in the delayed-matching-to-place (DMP)
      version of the Morris water maze and be more distracted by exposure to a novel
      stimulus during recall trials. It also addressed whether dietary supplementation
      with long-chain polyunsaturated fatty acids (LCPUFA) during development would
      increase brain docosahexaenoic acid (DHA) and improve SHR behavioral performance.
      Beginning at weaning (21 days), male SHR and WKY were fed either a control or
      LCPUFA supplemented diet [0.5% arachidonic acid (AA) and 0.9% DHA], and
      behavioral testing began at 8 weeks. The first three tasks comprised a series of
      problems, each consisting of an initial search trial and subsequent recall
      trials. The intertrial interval (ITI) between the search and recall trial was
      either 60 s or 60 min. Surprisingly, in contrast to SHR, WKY did not appear to
      use a spatial short-term memory strategy to solve the problem. Notwithstanding,
      the performance of both strains was affected by the delay, such that they showed
      longer path lengths at the long compared with the short ITI. There was no effect
      of dietary supplementation on DMP performance. SHR fed the control diet were less
      responsive to a novel stimulus introduced on the first recall trial than WKY, and
      this tended to increase with supplementation. Analysis of brain fatty acid
      composition indicated that supplementation did increase DHA in the
      phosphatidylethanolamine fraction in WKY; however, in SHR, there was either no
      change (phosphatidylethanolamine) or paradoxical decreases (phosphatidylcholine
      and phosphatidyserine/phosphatidylinositol). Further research is needed to
      determine whether SHR are an appropriate model for studying a possible
      relationship between dietary LCPUFA and the behavioral symptoms of ADHD.

PMID- 12794780
TI  - Consent to research in arthritis: quantity of information versus quality.

PMID- 12794781
TI  - The cost effectiveness of rofecoxib and celecoxib in patients with osteoarthritis
      or rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the cost effectiveness of the cyclooxygenase 2 (COX-2)
      selective nonsteroidal antiinflammatory drug (NSAID) rofecoxib compared with
      naproxen and the COX-2 NSAID celecoxib compared with ibuprofen and diclofenac.
      METHODS: Cost-effectiveness analysis based on a 5-year Markov model. Probability
      estimates were derived from detailed data of 2 randomized trials and a systematic
      search of the medical literature. Utility estimates were obtained from 60
      randomly selected members of the general public. Cost estimates were obtained
      from Canadian provincial databases. Incremental cost-effectiveness ratios were
      calculated for patients at average risk of upper gastrointestinal (UGI) events
      and for high-risk patients with a prior history of a UGI event. Subjects were
      patients with osteoarthritis or rheumatoid arthritis (RA) where a decision has
      been made to treat with NSAIDs but who do not require low-dose aspirin. Main
      outcome measures were proportion of patients with clinical or complicated UGI
      events, quality-adjusted life expectancy, and life expectancy. RESULTS:
      Evaluation of rofecoxib versus naproxen in patients with RA at average risk
      resulted in costs per quality-adjusted life year (QALY) gained of $Can271,188.
      Celecoxib was dominated by diclofenac in average-risk patients. Both rofecoxib
      and celecoxib are cost-effective in high-risk patients. Analyses by age groups
      and assuming a threshold of Can$50,000 per QALY gained, suggest that rofecoxib or
      celecoxib would be cost-effective in patients aged over 76 and 81, respectively,
      without additional risk factors. CONCLUSION: Both rofecoxib and celecoxib are
      economically attractive in high risk and elderly patients. They are not
      economically attractive in patients at average risk. Coprescription of proton
      pump inhibitors with COX-2 NSAIDs is not economically attractive for patients at
      high risk.

PMID- 12794783
TI  - US incidence of juvenile dermatomyositis, 1995-1998: results from the National
      Institute of Arthritis and Musculoskeletal and Skin Diseases Registry.
AB  - OBJECTIVE: To estimate the incidence of juvenile dermatomyositis (juvenile DM) in
      the United States between 1995 and 1998. METHODS: Physician referrals to the
      National Institute of Arthritis and Musculoskeletal and Skin Diseases Juvenile
      Dermatomyositis Research Registry and the National Pediatric Rheumatology Disease
      Registry from Indiana University were utilized for a 2-source capture-recapture
      estimation of Juvenile DM annual incidence. RESULTS: For children 2-17 years of
      age, the estimated annual incidence rates from 1995 to 1998 in the US ranged from
      2.5 to 4.1 juvenile DM cases per million children, and the 4-year average annual
      rate was 3.2 per million children (95% confidence interval 2.9-3.4). Estimated
      annual incidence rates by race were 3.4 for white non-Hispanics, 3.3 for African
      American non-Hispanics, and 2.7 for Hispanics. During the 4-year period of the
      study, completeness of ascertainment for the combined registries ranged from 56%
      to 86% and girls were affected more than boys (ratio 2.3:1). CONCLUSION: This
      study provides evidence for sex, and possibly racial differences in the risk of
      juvenile DM in the US.

PMID- 12794782
TI  - The effects of physician specialty and patient comorbidities on the use and
      discontinuation of coxibs.
AB  - OBJECTIVE: To examine the effects of physician specialty and comorbidities on
      cyclooxygenase 2-selective nonsteroidal antiinflammatory drugs (NSAIDs; coxibs)
      utilization. METHODS: Medical records of 452 patients from a regional managed
      care organization with >/=3 consecutive NSAID prescriptions from June 1998 to
      April 2001 were abstracted. Multivariable adjusted associations between coxib
      initiation and discontinuation and patient and provider characteristics were
      examined. RESULTS: A total of 1,142 NSAID prescriptions were written over 9,398
      total patient-months of followup. Compared with patients seeing family or general
      practitioners, patients seeing rheumatologists (odds ratio [OR] 3.4, 95%
      confidence interval [95% CI] 2.1-5.7) and internists (OR 2.3, 95% CI 1.5-3.6)
      were significantly more likely to receive a coxib, as well as patients with a
      history of osteoarthritis (OR 2.6, 95% CI 1.7-3.8), gastrointestinal disease (OR
      2.3, 95% CI 1.2-4.5), and congestive heart failure (OR 4.1, 95% CI 1.0-16.4).
      Although specialists were more likely than generalists to prescribe coxibs, only
      family or general practitioners were significantly more likely to selectively use
      coxibs among their patients with a history of gastrointestinal disease. Fifty
      four percent of NSAID prescriptions were discontinued, and coxibs were
      significantly less likely to be discontinued than were traditional NSAIDs (OR
      0.6, 95% CI 0.5-0.8). CONCLUSION: Our findings suggest significantly greater, but
      perhaps less selective use of coxibs among specialists, even after accounting for
      important covariates. The initiation and discontinuation of coxibs was influenced
      by physician specialty and by patient risk factors.

PMID- 12794784
TI  - Exercise-related goals and self-efficacy as correlates of aquatic exercise in
      individuals with arthritis.
AB  - OBJECTIVE: To examine whether aquatic exercise-related goals, task self-efficacy,
      and scheduling self-efficacy are predictive of aquatic exercise attendance in
      individuals with arthritis. A secondary objective was to determine whether high
      attendees differed from low attendees on goals and self-efficacy. METHODS: The
      sample comprised 216 adults with arthritis (mean age 69.21 years). Measures
      included exercise-related goal difficulty and specificity, task and scheduling
      self-efficacy, and 8-week aquatic exercise attendance. RESULTS: Results of a
      multiple hierarchical regression analysis were significant (P < 0.01). Goal
      difficulty, specificity, and task self-efficacy were independent predictors of
      attendance (P < 0.05). A significant multivariate analysis of variance (P < 0.01)
      indicated that high attendees had higher task and scheduling self-efficacy and
      lower goal difficulty than did low attendees (P < 0.05). CONCLUSION: Support for
      the importance of exercise-related goal setting and self-efficacy was
      demonstrated. Implications pertain to the design of interventions to impact
      aquatic exercise.

PMID- 12794785
TI  - Operant behavioral treatment of fibromyalgia: a controlled study.
AB  - OBJECTIVE: To evaluate the efficacy of operant pain treatment for fibromyalgia
      syndrome (FMS) in an inpatient setting. METHODS: Sixty-one patients who fulfilled
      the American College of Rheumatology criteria for FMS were randomly assigned to
      the operant pain treatment group (OTG; n = 40) or a standardized medical program
      with an emphasis on physical therapy (PTG; n = 21). Pain assessments were
      performed before, immediately after, 6 months after, and 15 months after
      treatment. RESULTS: The OTG patients reported a significant and stable reduction
      in pain intensity, interference, solicitous behavior of the spouse, medication,
      pain behaviors, number of doctor visits, and days at a hospital as well as an
      increase in sleeping time. Sixty-five percent of the OTG compared with none of
      the patients in the PTG showed clinically significant improvement. CONCLUSION:
      These results suggest that operant pain treatment provided in an inpatient
      setting is an effective treatment for FMS, whereas a purely somatically oriented
      program may lead to a deterioration of the pain problem.

PMID- 12794786
TI  - Promising outcome of a hip school for patients with hip dysfunction.
AB  - OBJECTIVE: To evaluate, in an exploratory study, a hip school led by physical
      therapists for patients with hip dysfunction including pain. METHODS: Physicians
      in primary care and orthopedic units consecutively recruited patients by
      residential area to a treatment group (T group; n = 77) and a control group (C
      group; n = 68), mean age 61.8 years, 59 men, 86 women. Ninety-nine of the 145
      subjects had radiologic hip osteoarthritis. Outcome measures were the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Nottingham
      Health Profile (NHP). RESULTS: After hip school (6 months) the T group showed
      greater reduction on the subscales of pain and activity limitations (WOMAC) than
      the C group. The subscales sleep disturbances, pain, and physical mobility (NHP)
      showed improvement for the T group compared with at start. The results for the T
      group persisted after an additional 6 months. CONCLUSION: A hip school may reduce
      pain and activity limitations and improve health-related quality of life for
      patients with hip dysfunction including pain.

PMID- 12794787
TI  - Bacterial components in the synovial tissue of patients with advanced rheumatoid
      arthritis or osteoarthritis: analysis with gas chromatography-mass spectrometry
      and pan-bacterial polymerase chain reaction.
AB  - OBJECTIVE: To study the presence of bacterial components in the synovial tissue
      (ST) of patients with advanced rheumatoid arthritis (RA). METHODS: ST was
      collected during joint surgery from 41 RA patients. Tissue from 39 patients with
      osteoarthritis (OA), 4 patients with undifferentiated inflammatory arthritis
      (UA), and 3 cases of accidental deaths served as controls. The pan-bacterial
      polymerase chain reaction (PCR) with primers for the 23S ribosomal RNA (rRNA) and
      16S rRNA genes was used to detect bacterial DNA. In addition, synovial fluid (SF)
      samples from patients with chlamydial reactive arthritis (ReA) were also examined
      by the same method. The positive controls, bacterial DNA or ST spiked with
      different living bacteria, were analyzed alongside clinical samples. Most of the
      ST samples were also analyzed by gas chromatography-mass spectrometry (GC-MS) for
      determining the presence of bacteria-derived muramic acid. Strict precautions
      were followed in the clinics and the laboratory to prevent contamination.
      RESULTS: In GC-MS analysis, muramic acid was observed in the ST from 4 of 35 RA
      patients and from 2 of 14 OA patients, but not in ST from 2 patients with UA and
      3 cadavers. Bacterial DNA was not detected by either one of the PCR primers used
      in ST from 42 patients with RA and 39 patients with OA. However, 5 of 15 SF
      samples from ReA patients were PCR positive. The sensitivity of GC-MS to detect
      muramic acid was 2 pg/injected amount (227 pg muramic acid/mg ST), and that of
      the pan-bacterial PCR was 2-20 bacteria colony forming units/reaction.
      CONCLUSION: These results indicate that a bacterial component, muramic acid, is
      detectable by GC-MS in ST from a few patients with advanced RA or OA. However, no
      bacterial DNA was detectable by PCR.

PMID- 12794788
TI  - European Consensus Lupus Activity Measurement is sensitive to change in disease
      activity in childhood-onset systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate the European Consensus Lupus Activity Measurement (ECLAM)
      for responsiveness to change in disease activity when used in childhood-onset
      systemic lupus erythematosus (cSLE). To confirm the construct validity and to
      characterize the measurement properties of the ECLAM by assessing its ability to
      predict damage and steroid requirements. METHODS: The disease courses of 66 newly
      diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) were scored for all clinic visits and
      hospitalizations. Damage was assessed at the end of the followup period using the
      Systemic Lupus International Collaboration Clinics/American College of
      Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months
      after diagnosis, at the time of first flare, and 6 months after first flare was
      used to estimate responsiveness of the measures. Responsiveness was measured by
      the effect size, the effect size index, the standardized response mean, and the
      relative efficiency index (REI). The measurement properties of the ECLAM and
      SLEDAI over time were examined by comparing the ability of both measures to
      predict damage and oral steroid requirement. RESULTS: The ECLAM and SLEDAI are
      both responsive to change in disease activity irrespective of the statistic used.
      The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative
      disease activity as measured by the SLEDAI or the ECLAM are important predictors
      of damage. There are no statistically important differences between the 2
      measures with regard to their ability to predict steroid requirements.
      CONCLUSIONS: The ECLAM has construct validity in cSLE and, like the SLEDAI, is
      highly sensitive to clinically important change in disease activity. The ECLAM
      may be more responsive. The quantitative properties of the 2 measures are very
      similar. The SLEDAI likely remains the preferable disease activity measure for
      cSLE given its overall measurement properties and ease of use.

PMID- 12794789
TI  - Changes in self-efficacy and health status over 5 years: a longitudinal
      observational study of 306 patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate changes in self-efficacy and health status over 5 years
      in patients with rheumatoid arthritis (RA), the relationships between these
      changes, and the influence of baseline values on subsequent changes. METHODS: 306
      adult patients with RA, born in 1926 or later, were examined by questionnaire in
      1994 and again in 1999. We analyzed data regarding pain (visual analogue scale
      [VAS], Arthritis Impact Measurement Scale [AIMS2] symptom scale, Short Form-36
      [SF-36] pain scale), fatigue (VAS, SF-36 vitality scale), mental distress (AIMS2
      affect scale, SF-36 mental health scale) and self-efficacy (Arthritis Self
      Efficacy Scales for pain and for other symptoms). RESULTS: On group level, all
      health status measures were numerically somewhat improved, and self-efficacy
      slightly reduced. Changes in self-efficacy and in corresponding health status
      measures were significantly correlated. For patients with above average
      educational level self-efficacy for pain at baseline was positively correlated to
      improvement in pain measures. Good mental health at baseline was correlated to
      improvement in self-efficacy for other symptoms, but only for patients with below
      average educational level. CONCLUSION: Baseline self-efficacy seems to influence
      future level of perceived pain and baseline mental health status seems to
      influence future self-efficacy. These associations seem to be affected by level
      of education.

PMID- 12794790
TI  - Development of a work instability scale for rheumatoid arthritis.
AB  - OBJECTIVES: To explore the concept of work instability (WI), a state in which the
      consequences of a mismatch between an individual's functional abilities and the
      demands of his or her job could threaten continuing employment if not resolved,
      in people with rheumatoid arthritis (RA). To develop the Work Instability Scale
      (WIS). METHODS: WI in people with RA was explored through qualitative interviews,
      which were then used to generate items for the WIS. RESULTS: Through Rasch
      analysis and validation against a gold standard of expert vocational assessment,
      a short 23-item, self administered, RA WIS was developed. CONCLUSION: The WIS can
      be scored in 3 bands indicating low, medium, and high risk of work disability.

PMID- 12794791
TI  - Vertebral deformities in 229 female patients with rheumatoid arthritis:
      associations with clinical variables and bone mineral density.
AB  - OBJECTIVE: To examine the occurrence of vertebral deformities in female patients
      with rheumatoid arthritis (RA), and the relationship between vertebral
      deformities and bone mineral density (BMD) and between vertebral deformities and
      clinical variables. METHODS: Lateral radiographs of the spine were obtained in
      229 female patients with RA (mean age 63.4 years, range 51.4-73.6 years)
      recruited from a county RA register. Vertebral deformities were measured
      semiquantitatively by an experienced radiologist. A clinical examination
      including core measurements of disease activity and severity was performed, and
      BMD was measured at the spine (L2-L4) and hip. RESULTS: According to the
      statistical analysis, 49 patients were considered to have relevant vertebral
      deformities. The occurrence of vertebral deformities was independently associated
      with age, long-term corticosteroid use, and previous nonvertebral fracture, as
      well as reduced BMD. Our results failed to show any independent relationship
      between vertebral deformities and the activity or severity of disease.
      CONCLUSION: Corticosteroid use is an important marker of established osteoporosis
      in patients with RA. Additionally, there seems to be a consistent relationship
      between BMD and vertebral deformities in this patient group.

PMID- 12794792
TI  - Informed consent in a clinical trial of a novel treatment for rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the informed consent process for a clinical trial of
      intravenous doxycycline for rheumatoid arthritis. METHODS: Participants completed
      a self-administered questionnaire about the consent process at baseline and 16
      weeks following enrollment in a clinical trial. RESULTS: Respondents (n = 30)
      affirmed voluntary participation in the parent trial. Participants acknowledged
      hope and altruism as reasons for entering the trial more than expectation of
      personal benefit or outside influences. Many respondents did not understand
      randomization (14/30), placebos (15/30), or risks of study medications; 11/30
      respondents believed that the study drug was completely safe. CONCLUSION:
      Respondents generally understood the experimental nature of the trial and
      confirmed their participation was voluntary. However, gaps existed in
      participants understanding of trial design, raising the question of whether they
      were adequately informed about the research study prior to enrollment. Further
      education of potential participants in clinical trials may be required to achieve
      valid informed consent.

PMID- 12794793
TI  - A comparison of self-reports of distress and affective disorder diagnoses in
      rheumatoid arthritis: a receiver operator characteristic analysis.
AB  - OBJECTIVE: To compare 3 commonly used psychiatric symptom checklists (the Center
      for Epidemiological Studies Depression Scale [CES-D], the Positive and Negative
      Affect Schedule, and the Endler Multidimensional Anxiety Scales [EMAS]) to
      determine their sensitivity, specificity, and ability to discriminate between a
      disorder (Major Depression [MD], Generalized Anxiety Disorder [GAD]), and no
      disorder. To compare the checklists for their ability to discriminate between
      type of disorder (MD and GAD). To evaluate the discriminant ability of the
      subscales, particularly positive affect; whether the somatic items in the CES-D
      artificially inflate affective scores; and the optimal cut off score for the CES
      D. METHODS: We compared the 3 scales to diagnostic criterion of MD, GAD, and
      comorbid disorder using receiver operator characteristic (ROC) and logistic
      regression analyses. The sample consisted of a national panel of 415 individuals
      with rheumatoid arthritis (RA). RESULTS: Each of the scales had high sensitivity
      and specificity (areas under the curve: CES-D = 0.92, negative affect = 0.88,
      positive affect and EMAS = 0.82). The CES-D, however, demonstrated better
      sensitivity and specificity than the positive affect and the EMAS, but not the
      negative affect scale. CONCLUSION: All 3 self-reports have high combined
      sensitivity and specificity as measures of affective disorders among RA patients.

PMID- 12794794
TI  - Effects of disease management programs on functional status of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To perform a systematic review of the published literature on disease
      management of rheumatoid arthritis (RA) and to use meta-analysis to estimate the
      magnitude of benefit these programs have on functional status in patients with
      RA. METHODS: Computerized databases for English articles from 1966 to September
      2001 were searched. Two reviewers evaluated 1,029 published titles, identified 11
      studies meeting explicit inclusion criteria, and extracted data about study
      characteristics, interventions used, and outcomes measured. Pooled effect sizes
      for functional status were calculated using a random-effects model. RESULTS: Four
      out of 8 disease management programs showed significant improvements in
      functional status; however, the pooled effect size (ES) was small and
      statistically non-significant (ES 0.27; 95% confidence interval [95% CI] -0.01,
      0.54). Studies with longer intervention durations (>5 weeks) had significantly
      improved patient functional status (ES 0.49; 95% CI 0.12, 0.86), compared with
      studies with shorter intervention durations (</=5 weeks, ES 0.13; 95% CI -0.25,
      0.52). CONCLUSIONS: There were limited data to support or refute the
      effectiveness of disease management programs in improving functional status in
      patients with RA. Additional studies are needed to confirm if a more intensive
      intervention may be of benefit to patients with RA, as suggested by our study.

PMID- 12794796
TI  - Improvement in Sjogren's syndrome following therapy with rituximab for marginal
      zone lymphoma.

PMID- 12794795
TI  - The epidemiology of the primary systemic vasculitides in northwest Spain:
      implications of the Chapel Hill Consensus Conference definitions.
AB  - OBJECTIVE: To assess the epidemiology of the primary systemic vasculitides (PSV)
      in a well-defined population of southern Europe over a 14-year period using the
      Chapel Hill Consensus Conference (CHCC) definitions. METHODS: The case records of
      all patients 15 years or older with vasculitis diagnosed between January 1988 and
      December 2001 at a single reference hospital in the Lugo region of northwest
      Spain were reviewed. Incidence rates were age- and sex-adjusted to the European
      standard population. Patients were classified as having PSV according to the CHCC
      definitions. RESULTS: Fifty-four Lugo residents (29 men) fulfilled the CHCC
      definitions for PSV. The mean age was 60.7 +/- 13.5 years (men: 61.0 +/- 13.4;
      women: 60.4 +/- 13.8 years). The overall annual incidence of PSV was
      13.07/million (95% confidence interval [95% CI] 8.89-19.22). PSV were slightly
      more common in men. The age-specific incidence showed a clear increase with age.
      A peak in the 55-64 year age group for the whole group of patients with PSV was
      observed (34.9/million; 95% CI 28.6-42.6). Nonrandom periodical peaks of
      incidence every 3 years were only observed when the group of PSV was considered
      as a whole (P = 0.040). The annual incidence was 2.95/million (95% CI 1.44-6.05)
      for Wegener's granulomatosis (WG) and 7.91/million (95% CI 4.74-13.20) for
      microscopic polyangiitis (MPA) (P = 0.035). None of the patients with Churg
      Strauss syndrome (n = 4) lived in a rural area. CONCLUSION: Our observations
      support an increasing incidence of PSV with age. In patients from northwest Spain
      defined by the CHCC definitions, MPA is more common than WG.

PMID- 12794797
TI  - Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl
      70, and nucleolar antibodies.

PMID- 12794798
TI  - Aspiration and injection therapies for joints.

PMID- 12794799
TI  - Cerebral amyloid angiopathy associated with primary angiitis of the central
      nervous system: report of 2 cases and review of the literature.

PMID- 12794800
TI  - Evidence for the benefit of aerobic and strengthening exercise in rheumatoid
      arthritis.

PMID- 12794801
TI  - Exercise and fitness in children with arthritis: evidence of benefits for
      exercise and physical activity.

PMID- 12794803
TI  - Work group recommendations: 2002 Exercise and Physical Activity Conference, St.
      Louis, Missouri. Session V: evidence of benefit of exercise and physical activity
      in arthritis.

PMID- 12794802
TI  - Muscle dysfunction and effective rehabilitation of knee osteoarthritis: what we
      know and what we need to find out.

PMID- 12794804
TI  - Community-based physical activity intervention.

PMID- 12794805
TI  - Arthritis Foundation community-based physical activity programs: effectiveness
      and implementation issues.

PMID- 12794806
TI  - Implementing the National Arthritis Action Plan: new population-based approaches
      to increasing physical activity among people with arthritis.

PMID- 12794808
TI  - Work group recommendations: 2002 Exercise and Physical Activity Conference, St.
      Louis, Missouri. Session VI: population approaches to health promotion and
      disability prevention through physical activity.

PMID- 12794810
TI  - Does vascular endothelial growth factor play a role in interleukin-6 receptor
      antagonist therapy for rheumatoid arthritis?

PMID- 12794811
TI  - C-reactive protein as a regulator of autoimmunity and inflammation.

PMID- 12794812
TI  - The role of leukotrienes in alveolitis associated with scleroderma.

PMID- 12794813
TI  - Add-on or step-up trials for new drug development in rheumatoid arthritis: a new
      standard?

PMID- 12794814
TI  - Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy.

PMID- 12794815
TI  - Etanercept added to background methotrexate therapy in patients with rheumatoid
      arthritis: continued observations.
AB  - OBJECTIVE: To observe the long-term safety and efficacy of combination therapy
      with etanercept and methotrexate in patients with rheumatoid arthritis (RA), and
      to determine whether the addition of etanercept allowed reductions in
      methotrexate or corticosteroid dosages while maintaining a clinical response.
      METHODS: Patients with RA who received methotrexate plus etanercept in a previous
      randomized, placebo-controlled trial were offered the opportunity to enroll in an
      open-label extension study for further evaluation of treatment with etanercept
      and methotrexate. RESULTS: Seventy-nine of the 89 patients in the original
      blinded study enrolled in the extension study, and 65 of these patients continue
      in the study. Patients have received etanercept therapy for up to 47 months
      (median 44 months). The types and rate of adverse events noted during the
      extension trial were similar to those observed in the controlled trial. At the 3
      year assessment, 77% of the 57 patients available for evaluation met American
      College of Rheumatology 20% (ACR20) criteria for improvement in RA, 47% met the
      ACR50 criteria, and 23% met the ACR70 criteria. Of the 36 patients assessed at 3
      years in the extension study, 30 (83%) were able to decrease their dosages of
      corticosteroids, and 20 (56%) were able to discontinue corticosteroid therapy. At
      3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and
      methotrexate therapy was discontinued in 19 patients (29%). CONCLUSION: In this
      observational continuation study, the addition of etanercept to background
      methotrexate provided sustained clinical benefit over a median period of 44
      months. With etanercept therapy, there were trends toward dosage reduction or
      discontinuation of methotrexate and corticosteroids, without apparent worsening
      of ACR response rates. Compared with the controlled trial, no increases in the
      rate of adverse events were observed.

PMID- 12794816
TI  - Clinical responses to tumor necrosis factor alpha antagonists do not show a
      bimodal distribution: data from the Stockholm tumor necrosis factor alpha
      followup registry.
AB  - OBJECTIVE: To study the distribution of clinical responses to treatment with the
      tumor necrosis factor alpha (TNFalpha) antagonists etanercept and infliximab, and
      in particular, to determine whether there is a biologically meaningful
      distinction between responders and nonresponders. METHODS: Among patients in the
      Stockholm TNFalpha Followup Registry, we analyzed the clinical responses to
      etanercept and infliximab, using the American College of Rheumatology (ACR) core
      set of outcome measures. For each parameter, the absolute change (value at
      baseline - current value) and the percentage change ([absolute change]/[value at
      baseline] x 100) from baseline were calculated. The results were plotted as
      histograms and inspected visually, and the distributions were statistically
      compared with computer-generated normal distributions. RESULTS: Absolute and
      relative changes in outcomes on the ACR core set of measures in 406 patients
      receiving etanercept or infliximab were studied. All but a few of these analyses
      yielded normal or somewhat skewed distributions. The statistical analyses did not
      detect any non-normal distributions, and visually, the distributions did not
      appear to be bimodal. CONCLUSION: The clinical response to TNFalpha blockade
      displays a normal or skewed, but not bimodal, distribution. The frequently
      encountered perception that a clear distinction can be made between responders
      and nonresponders is not borne out. These relatively straightforward findings
      imply that the biologic mechanisms determining responsiveness to TNFalpha
      blockade are multifactorial and may also have important implications for
      regulatory guidelines pertaining to treatment with these biologic agents.

PMID- 12794817
TI  - Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis
      patients sensitizes the pituitary gland and favors adrenal androgen secretion.
AB  - OBJECTIVE: New insights into the role of tumor necrosis factor (TNF) in the
      pathogenesis of rheumatoid arthritis (RA) have expanded our understanding about
      the possible mechanisms by which anti-TNF antibody therapy reduces local synovial
      inflammation. Beyond local effects, anti-TNF treatment may modulate systemic
      antiinflammatory pathways such as the hypothalamic-pituitary-adrenal (HPA) axis.
      This longitudinal anti-TNF therapy study was designed to assess these effects in
      RA patients. METHODS: RA patients were given 5 infusions of anti-TNF at weeks 0,
      2, 6, 10, and 14, with followup observation until week 16. We measured serum
      levels of interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), 17
      hydroxyprogesterone (17[OH]progesterone), cortisol, cortisone, androstenedione
      (ASD), dehydroepiandrosterone (DHEA), and DHEA sulfate in 19 RA patients.
      RESULTS: Upon treatment with anti-TNF, we observed a fast decrease in the levels
      of serum IL-6, particularly in RA patients who did not receive parallel
      prednisolone treatment (P = 0.043). In these RA patients who had not received
      prednisolone, the mean serum ACTH levels sharply increased after every injection
      of anti-TNF, which indicates a sensitization of the pituitary gland (not observed
      for the adrenal gland). During treatment, the ratio of serum cortisol to serum
      ACTH decreased, which also indicates a sensitization of the pituitary gland (P <
      0.001), and which was paralleled by constant cortisol secretion. The adrenal
      androgen ASD significantly increased relative to its precursor 17(OH)progesterone
      (P = 0.013) and relative to cortisol (P = 0.009), which indicates a normalization
      of adrenal androgen production. The comparison of patients previously treated
      with prednisolone and those without previous prednisolone revealed marked
      differences in the central and adrenal level of this endocrine axis during long
      term anti-TNF therapy. CONCLUSION: Long-term therapy with anti-TNF sensitizes the
      pituitary gland and improves adrenal androgen secretion in patients who have not
      previously received prednisolone treatment. These changes are indicative of
      normalization of the HPA axis and must therefore be considered as evidence of an
      additional antiinflammatory influence of anti-TNF treatment in patients with RA.

PMID- 12794818
TI  - The efficacy and safety of leflunomide in patients with active rheumatoid
      arthritis: a five-year followup study.
AB  - OBJECTIVE: To investigate the efficacy and safety of leflunomide beyond 2 years
      in a multinational, open-label extension of 2 phase III double-blind studies.
      METHODS: Patients with rheumatoid arthritis (RA) who received leflunomide (100
      mg/day for 3 days, 10 mg/day or 20 mg/day thereafter) in the 2 phase III studies
      and who completed 2 years of treatment were offered inclusion in the open-label
      extension phase and were maintained on the same dosage of leflunomide. The
      American College of Rheumatology revised criteria for 20% improvement (ACR20),
      ACR50, and ACR70 response rates, the Stanford Health Assessment Questionnaire
      (HAQ) scores, and C-reactive protein (CRP) levels were assessed. Safety measures
      included monitoring of adverse events and laboratory values. RESULTS: A total of
      214 patients (mean age 57 years) were treated with leflunomide for >2 years;
      74.8% of the patients were female. The mean disease duration was 4.1 years (range
      0.1-26.6 years), and in 44% of patients, RA was first diagnosed within 2 years of
      entry into the phase III studies. The mean duration of leflunomide treatment was
      4.6 years (range 2.8-5.8 years), and 32% of patients had received no previous
      treatment with disease-modifying antirheumatic drugs. ACR20, ACR50, and ACR70
      response rates and HAQ scores at 1 year were maintained through year 4 or until
      the end point. No new types of adverse events were observed, and liver function
      was normal at baseline and at the end point in the majority of patients.
      CONCLUSION: The improvements in both functional ability and physician-based
      efficacy measures seen with leflunomide after 1 year were maintained for up to 5
      years (maximum treatment duration 5.8 years), demonstrating that the early
      efficacy of leflunomide in patients with RA is sustained long-term, and that the
      long-term safety profile of leflunomide is no different from that observed in
      phase III trials.

PMID- 12794820
TI  - Predicting mortality in patients with rheumatoid arthritis.
AB  - OBJECTIVE: A number of different variables have been proposed as risk factors for
      mortality in patients with rheumatoid arthritis (RA), but limited prospective
      information on the magnitude of their effects is available. This study was
      undertaken to evaluate the relative predictive strength and usefulness of a wide
      range of variables on the risk of mortality in a large, long-term, prospectively
      studied cohort of patients with RA. METHODS: Over a 20-year period of followup
      beginning in 1981, 1387 consecutive RA patients were seen in a single clinic. A
      wide range of clinical and demographic assessments were recorded and entered into
      a computer database at the time of each clinical assessment. Assessment of
      predictive strength included determination of standardized and fourth-versus
      first-quartile odds ratios (ORs), goodness-of-fit measures, and contributing
      fraction. RESULTS: The Health Assessment Questionnaire (HAQ) disability index was
      the strongest clinical predictor of mortality. A 1-SD change in the HAQ resulted
      in a much larger increase in the odds ratio for mortality compared with a 1-SD
      change in global disease severity, the next most powerful predictor of mortality
      (OR 2.31 versus 1.83). Considering the contributing fraction, mortality would be
      reduced by 50% for the HAQ and by 33% for global disease severity if patients in
      the fourth quartile for these variables could be switched to the first quartile.
      Global disease severity, pain, depression, anxiety, and laboratory and
      radiographic features were significantly weaker predictors. Disease duration,
      nodules, and tender joint count were clinical variables that provided very little
      predictive information. In multivariable analyses, HAQ and other patient self
      report measures were significantly better predictors than were radiographic and
      laboratory variables. A single baseline observation provided the least
      information, with substantially increasing predictive ability associated with 1
      year, 2-year, and all-time point followup observations (time-varying covariates).
      CONCLUSION: In this large 20-year study from routine clinical practice, the HAQ
      was the most powerful predictor of mortality, followed by other patient self
      report variables. Laboratory, radiographic, and physical examination data were
      substantially weaker in predicting mortality. We recommend that clinicians
      collect patient self-report data, since they produce more useful clinical outcome
      information than other available clinical measures.

PMID- 12794819
TI  - Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth
      factor production in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether interleukin-6 (IL-6) is a regulator of vascular
      endothelial growth factor (VEGF) in rheumatoid arthritis (RA). METHODS: Serum
      VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of
      maintenance therapy with humanized anti-IL-6 receptor monoclonal antibody (anti
      IL-6R mAb). VEGF secreted by RA synovial fibroblasts cultured in the presence of
      IL-6, IL-1beta, and/or tumor necrosis factor alpha (TNFalpha) was measured. The
      inhibitory effect of anti-IL-6R mAb, recombinant IL-1 receptor antagonist (IL
      1Ra), and anti-TNFalpha mAb on VEGF production was also examined. RESULTS: Serum
      VEGF levels in RA patients before anti-IL-6R mAb therapy were significantly
      higher than those in healthy controls (P < 0.0005). Treatment of RA patients with
      anti-IL-6R mAb normalized serum VEGF levels. In the in vitro study, IL-6 and IL
      1beta each induced a slight amount of VEGF production in synovial cells, but
      TNFalpha did not. Although VEGF-inducing activity of these cytokines was not
      remarkable when they were added alone, IL-6 acted synergistically with IL-1beta
      or TNFalpha to induce VEGF production. There was no synergistic effect between IL
      1beta and TNFalpha. In the presence of all of these cytokines, anti-IL-6R mAb
      eliminated the synergistic effect of IL-6, IL-1beta, and TNFalpha, while IL-1Ra
      or anti-TNFalpha mAb did not. CONCLUSION: Anti-IL-6R mAb therapy reduced VEGF
      production in RA. IL-6 is the pivotal cytokine that induces VEGF production in
      synergy with IL-1beta or TNFalpha, and this may be the mechanism by which IL-6
      blockade effectively suppresses VEGF production in synovial fibroblasts.

PMID- 12794821
TI  - Lymphoma subtypes in patients with rheumatoid arthritis: increased proportion of
      diffuse large B cell lymphoma.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of
      developing malignant lymphoma. It is not clear whether the increase is confined
      to certain subtypes of lymphomas. Immunosuppressive therapy and Epstein-Barr
      virus (EBV) have been linked to the development of these lymphomas. To gain
      information about the baseline pattern of lymphoma subtypes in RA before the
      current widespread use of immunosuppressive drugs, we examined the distribution
      of lymphoma subtypes and the presence of EBV in a cohort of RA patients with a
      low frequency and duration of treatment with immunosuppressive drugs. METHODS: By
      linking data from the Swedish Hospital Discharge Register and the Swedish Cancer
      Register, 42 cases of lymphoma were identified among 11683 patients with RA in
      the Uppsala Health Care Region between 1964 and 1984. The medical records and
      paraffin-embedded lymphoma tissues were collected, and the lymphomas were
      reclassified using the World Health Organization classification. In situ
      hybridization was used to detect EBV. RESULTS: Tissues from 35 patients were
      reviewed. Non-Hodgkin's lymphoma (NHL) was found in 33 patients and Hodgkin's
      lymphoma in 2 patients. There was an increased frequency of diffuse large B cell
      lymphoma (DLBCL) (22 of 33 NHL patients, 67%) compared with that in the general
      population (30-40%). EBV was detected in 5 of 30 examined lymphomas from patients
      (17%). Twenty of the 22 DLBCL patients had RA with medium or high inflammatory
      activity, and 6 had been treated with a disease-modifying antirheumatic drug for
      >or=1 year. CONCLUSION: The findings of this study suggest an increased incidence
      of one specific lymphoma subtype, DLBCL, in RA patients, as well as a possible
      association with RA disease activity.

PMID- 12794822
TI  - Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in
      rheumatoid arthritis synoviocytes by taurine chloramine.
AB  - OBJECTIVE: To investigate the effects of taurine chloramine (Tau-Cl), a
      chlorinated derivative of the amino acid taurine, on the expression of
      cyclooxygenase (COX) isoenzymes and prostaglandin E(2) (PGE(2)) synthesis in
      rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHODS: FLS,
      isolated from the synovial tissue of RA patients, were treated in vitro with
      either interleukin-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500
      microM Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein
      (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase
      chain reaction) levels. The concentration of PGE(2) was measured by competitive
      acetylcholinesterase enzyme immunoassay. RESULTS: Resting FLS expressed mRNA
      encoding both COX-1 and COX-2, but only COX-1 was present at the protein level.
      These cells produced negligible amounts of PGE(2). Upon stimulation with IL
      1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the
      enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl,
      significant inhibition of IL-1beta-triggered COX-2 mRNA and protein, and a
      related decrease in PGE(2) production, was observed. In contrast, no significant
      changes in COX-1 mRNA and protein levels were noted. CONCLUSION: Tau-Cl inhibits
      IL-1beta-triggered elevation of COX-2 and generation of PGE(2) by RA FLS. These
      results expand the spectrum of known antiinflammatory activities of this
      compound.

PMID- 12794823
TI  - Asymmetric knee loading in advanced unilateral hip osteoarthritis.
AB  - OBJECTIVE: Subjects with unilateral end-stage hip osteoarthritis (OA) who undergo
      total hip replacement (THR) preferentially require subsequent replacement of the
      contralateral knee compared with the ipsilateral knee. We investigated whether
      this nonrandom, preferential evolution of lower extremity OA from the hip to the
      contralateral knee joint may be related to asymmetries in dynamic joint loading
      at the knees, particularly the peak external knee adduction moment, which has
      been associated with the progression of knee OA. METHODS: Gait analysis was
      performed on 50 subjects who were preoperative for unilateral THR. Twenty-two of
      these subjects were reevaluated postoperatively 10-23 months after undergoing
      successful THR. At each analysis, dynamic joint loads in the contralateral knee
      were compared with those in the ipsilateral knee. RESULTS: Prior to THR, the peak
      external knee adduction moment and peak medial compartment load were
      significantly higher in the contralateral knee. This asymmetry persisted after
      THR. CONCLUSION: Subjects with unilateral end-stage hip OA preferentially require
      subsequent replacement of the contralateral knee, as compared with the
      ipsilateral knee. Among patients with unilateral end-stage hip OA, the
      contralateral knee is subjected to higher dynamic joint loads than is the
      ipsilateral knee, and this asymmetric loading persists long after subjects have
      undergone successful THR. Biomechanical factors appear to be involved in the
      multiarticular evolution of OA of the lower extremities.

PMID- 12794824
TI  - Hsp70 prevents nitric oxide-induced apoptosis in articular chondrocytes.
AB  - OBJECTIVE: To deliver and overexpress the hsp70 gene in cultured chondrocytes to
      investigate its effect on nitric oxide (NO)-induced apoptosis of chondrocytes.
      METHODS: Primary chondrocyte cultures were established from rabbit joints. The
      cells were transduced with an empty adenovirus vector (Ax1w) or an adenovirus
      vector harboring the hsp70 E-tag fusion gene (AxSHEwt). Apoptosis was induced by
      sodium nitroprusside (SNP) dihydrate, which generates NO, or by staurosporine,
      which is a proapoptotic agent dependent upon Bax or Bak protein. Cell viability
      and apoptosis induction were estimated by lactate dehydrogenase (LDH) assay,
      Hoechst 33342 staining, or the TUNEL method. To study Hsp70, cytochrome c, and
      caspase 3, Western blot analyses were performed. RESULTS: The AxSHEwt-transduced
      cells escaped apoptosis, as revealed by the LDH assay, Hoechst 33342 staining,
      and the TUNEL method. A massive amount of the tagged Hsp70 was demonstrated in
      the AxSHEwt-transduced chondrocytes but not in control cells. Hsp70 did not
      affect the cytosolic cytochrome c level, but appeared to have obstructed the
      activation of caspase 3. CONCLUSION: Experimentally overexpressed Hsp70 almost
      completely inhibited NO- or staurosporine-induced apoptosis in primary
      chondrocytes.

PMID- 12794825
TI  - Mediation of interleukin-1beta-induced transforming growth factor beta1
      expression by activator protein 4 transcription factor in primary cultures of
      bovine articular chondrocytes: possible cooperation with activator protein 1.
AB  - OBJECTIVE: Interleukin-1 (IL-1) and transforming growth factor beta1 (TGFbeta1)
      play major roles in osteoarticular diseases, exerting opposite effects on both
      the catabolism and anabolism of cartilage matrix. Previous findings suggest that
      IL-1 and TGFbeta1 could function in a feedback interaction. However, the effect
      exerted by IL-1 on expression of TGFbeta by articular chondrocytes is, so far,
      poorly understood. The present study was carried out to determine the influence
      of IL-1beta on the expression of TGFbeta1 by bovine articular chondrocytes (BACs)
      in primary culture. METHODS: BAC primary cultures were treated with IL-1beta, and
      TGFbeta1 messenger RNA (mRNA) steady-state levels and protein expression were
      measured by real-time reverse transcription-polymerase chain reaction and enzyme
      linked immunosorbent assay, respectively. Transient transfection of TGFbeta1 gene
      promoter constructs was performed to delineate the DNA sequences that mediate the
      IL-1beta effect. Electrophoretic mobility shift assays (EMSAs) and supershift
      analysis were used to characterize the transcription factors binding to these
      sequences. RESULTS: Cultured BACs responded to IL-1beta exposure by exhibiting an
      increase of TGFbeta1 expression at both the mRNA and protein levels. The effect
      was found to be mediated by a major 80-bp sequence located between -732 and -652
      upstream of the transcription initiation site. EMSA and supershift analysis
      revealed that the transcription factors activator protein 4 (AP-4) and AP-1
      specifically bound to the -720/-696 part of this sequence under IL-1beta
      treatment. Overexpression of AP-4 in the BAC cultures resulted in stimulation of
      the transcriptional activity of the -732/+11 TGFbeta1 promoter construct through
      the same IL-1beta-responsive element. CONCLUSION: IL-1beta induces an increase of
      TGFbeta1 in articular chondrocytes through activation of AP-4 and AP-1 binding to
      the TGFbeta1 gene promoter. These findings may help us understand the role of IL
      1beta in the disease process. Notwithstanding its deleterious effect on
      cartilage, IL-1 could initiate the repair response displayed by injured cartilage
      in the early stages of osteoarthritis through its ability to enhance TGFbeta1
      expression by local chondrocytes.

PMID- 12794826
TI  - In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in
      rabbit experimental osteoarthritis is associated with a reduction in the
      development of structural changes.
AB  - OBJECTIVE: The primary aim of this study was to investigate, using an
      experimental rabbit model of osteoarthritis (OA), the effect of a selective
      mitogen-activated protein kinase kinase 1/2 (MEK-1/2) inhibitor, PD 198306, on
      the development of structural changes. Additional aims were to assess the effects
      of the inhibitor on levels of phosphorylated extracellular signal-regulated
      kinase 1/2 (phospho-ERK-1/2) and matrix metalloproteinase 1 (MMP-1; collagenase
      1) in OA chondrocytes. METHODS: After surgical sectioning of the anterior
      cruciate ligament of the right knee joint, rabbits with OA were separated into 3
      experimental groups: oral treatment with placebo or with PD 198306 at a
      therapeutic concentration of 10 mg/kg/day or 30 mg/kg/day. Each treatment started
      immediately after surgery. The animals were killed 8 weeks after surgery.
      Macroscopic and histologic studies were performed on the cartilage and synovial
      membrane. The levels of phospho-ERK-1/2 and MMP-1 in OA cartilage chondrocytes
      were evaluated by immunohistochemistry. Normal, untreated rabbits were used as
      controls. RESULTS: OA rabbits treated with the highest dosage of MEK-1/2
      inhibitor showed decreases in the surface area (size) of cartilage macroscopic
      lesions (P < 0.002) and in osteophyte width on the lateral condyles (P = 0.05).
      Histologically, the severity of synovial inflammation (villous hyperplasia) was
      also reduced (P < 0.02). In cartilage from placebo-treated OA rabbits, a
      significantly higher percentage of chondrocytes in the superficial layer stained
      positive for phospho-ERK-1/2 and MMP-1 compared with normal controls. Rabbits
      treated with the highest dosage of PD 198306 demonstrated a significant and dose
      dependent reduction in the level of phospho-ERK-1/2 and a lower level of MMP-1.
      CONCLUSION: This study demonstrates that, in vivo, PD 198306, a selective
      inhibitor of MEK-1/2, can partially decrease the development of some of the
      structural changes in experimental OA. This effect was associated with a
      reduction in the level of phospho-ERK-1/2 in OA chondrocytes, which probably
      explains the action of the drug.

PMID- 12794827
TI  - Effects of antiinflammatory drugs on arthritic cartilage: a high-frequency
      quantitative ultrasound study in rats.
AB  - OBJECTIVE: To evaluate the ability of 55-MHz quantitative ultrasound (US) to
      detect the in vivo effects of experimental arthritis, as well as those of two
      antiinflammatory drugs, naproxen (NPX) and dexamethasone (DEX), on cartilage and
      subchondral bone. METHODS: Arthritis was induced in both knees of 108 rats by
      intraarticular injection of zymosan (ZYM). Two groups of arthritic rats (n = 36
      per group) were treated daily with either NPX (10 mg/kg/day) or DEX (0.1
      mg/kg/day). Using a 3-dimensional US microscope, patellae were explored in vitro
      on days 5, 14, and 21 after injections. US assessment included the analysis of
      quantitative indices of local modifications involving cartilage and bone:
      integrated reflection coefficient (IRC) from the cartilage surface and apparent
      integrated backscatter from the cartilage internal structure (cartilage matrix)
      (AIB(cartilage)) and the cartilage-bone interface (AIB(bone)). RESULTS: ZYM
      induced articular surface fibrillation that resulted in a decrease in IRC at all
      times (P < 0.02) and in an increase in AIB(bone) on days 5 and 14 (P < 0.005).
      Fibrillation was not changed by NPX administration, while it disappeared
      following DEX treatment. Cartilage-bone interface alterations were prevented by
      DEX and partially compensated for by NPX. Cartilage matrix echogenicity decreased
      with time in all groups due to maturation (P < 0.05), except in DEX-treated rats.
      CONCLUSION: Quantitative 55 MHz US allowed detection of early cartilage and bone
      lesions due to experimental arthritis, and also allowed detection of the effects
      of antiinflammatory drugs. NPX seemed to have an effect on subchondral bone
      lesions, but not on cartilage. DEX appeared to repair articular surface and bone,
      but prevented animal growth and cartilage maturation.

PMID- 12794828
TI  - Delayed lupus onset in (NZB x NZW)F1 mice expressing a human C-reactive protein
      transgene.
AB  - OBJECTIVE: Human C-reactive protein (CRP) binds apoptotic cells and alters blood
      clearance of injected chromatin in mice. To test whether CRP participates in the
      pathogenesis of systemic lupus erythematosus (SLE), we examined disease
      development in lupus-prone (NZB x NZW)F(1) (NZB/NZW) mice expressing a human CRP
      transgene (hCRPtg/BW). METHODS: Mortality was monitored, proteinuria was
      determined by dipstick, and serum levels of human CRP and anti-double-stranded
      DNA (anti-dsDNA) were determined by enzyme-linked immunosorbent assay in NZB/NZW
      and hCRPtg/BW mice. Thin sections of kidneys were analyzed by immunofluorescence
      microscopy to compare deposition of IgG, IgM, C3, and human CRP, and electron
      microscopy was used to reveal differences in ultrastructure. In situ
      hybridization was performed to detect human CRP messenger RNA expression.
      RESULTS: The hCRPtg/BW mice had less proteinuria and longer survival than NZB/NZW
      mice. They also had lower IgM and higher IgG anti-dsDNA titers than NZB/NZW mice,
      although the differences were transient and small. In hCRPtg/BW mice,
      accumulation of IgM and IgG in the renal glomeruli was delayed, reduced, and more
      mesangial than in NZB/NZW mice, while end-stage accumulation of IgG, IgM, and C3
      in the renal cortex was prevented. There was less glomerular podocyte fusion,
      basement membrane thickening, mesangial cell proliferation, and occlusion of
      capillary lumens in hCRPtg/BW mice, but dense deposits in the mesangium were
      increased. With disease progression in hCRPtg/BW mice, there was little rise in
      the plasma CRP level, but CRP in the kidneys became increasingly apparent due to
      local, disease-independent, age-related expression of the transgene. CONCLUSION:
      In hCRPtg/BW mice, CRP protects against SLE by increasing blood and mesangial
      clearance of immune complexes and by preventing their accumulation in the renal
      cortex.

PMID- 12794829
TI  - Differential control of CD22 ligand expression on B and T lymphocytes, and
      enhanced expression in murine systemic lupus.
AB  - OBJECTIVE: CD22, a B cell-restricted transmembrane glycoprotein, regulates B cell
      antigen receptor signaling upon interaction with alpha2,6-linked sialic acid
      bearing glycans, which act as ligands and are expressed on B and T cells. In this
      study, we investigated how the expression of CD22 ligand (CD22L) is modulated
      following lymphocyte activation or during the course of systemic lupus
      erythematosus (SLE). METHODS: The expression levels of CD22L on B and T cells in
      nonautoimmune mice were assessed by flow cytometric analysis using a soluble
      recombinant form of CD22, following stimulation with antigen or mitogen in vitro.
      In addition, the expression levels of CD22L on circulating lymphocytes were
      correlated with the progression of SLE in lupus-prone mice. RESULTS: We observed
      a constitutive expression of CD22L on mature B cells, but not T cells, in
      nonautoimmune mice. However, CD22L levels were up-regulated selectively on T
      cells (but not B cells) stimulated with antigens in vitro, while their expression
      levels on B cells was up-modulated following polyclonal activation with
      lipopolysaccharide. Furthermore, expression of CD22L was increased on circulating
      B cells (and to a lesser extent on T cells) in parallel with progression of SLE
      in several different lupus-prone mice and in a cohort of (C57BL/6 x [NZB x
      C57BL/6.Yaa]F(1)) backcross mice. CONCLUSION: The expression of CD22L is
      differentially regulated in B and T cells, and high expression of CD22L on
      circulating B cells is a marker for development of severe SLE, suggesting a role
      for CD22-CD22L interactions in SLE as well as in the regulation of humoral
      immunity.

PMID- 12794830
TI  - A thrombin-cross-reactive anticardiolipin antibody binds to and inhibits the
      anticoagulant function of activated protein C.
AB  - OBJECTIVE: To test the hypotheses that some thrombin-reactive anticardiolipin
      antibodies (aCL) may bind to protein C (PC) and/or activated PC (APC), and that
      some of the PC- and APC-reactive aCL may inhibit PC activation and/or the
      function of APC. METHODS: We studied the reactivity of patient-derived monoclonal
      aCL with PC and APC. We examined the effects of the reactive antibodies on PC
      activation and on the activity of APC in plasma coagulation. RESULTS: Five of 5
      patient-derived, thrombin-reactive monoclonal aCL bound to PC and APC. In
      addition, 1 patient-derived monoclonal antiprothrombin antibody (APT) that
      displayed aCL activity and reacted with thrombin also bound to PC and APC. Of
      these 6 PC- and APC-reactive aCL/APT, all failed to inhibit PC activation, but 1
      (CL15) shortened the plasma coagulation time in the presence of exogenous APC and
      thus inhibited the anticoagulant function of APC. CONCLUSION: Most of the
      thrombin-reactive aCL in patients with antiphospholipid syndrome may bind to PC
      and APC. Of the APC-reactive aCL, some (like CL15) may inhibit the anticoagulant
      function of APC and are thus likely to be prothrombotic in the host.

PMID- 12794831
TI  - Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases
      of childhood.
AB  - OBJECTIVE: To find further evidence of the association of parvovirus B19
      infection with juvenile rheumatic diseases, and to get new insights into the
      immunopathogenesis of these diseases. METHODS: Paired serum and synovial fluid
      samples from 74 children with rheumatic disease were analyzed with respect to
      their content of viral DNA and antibodies directed against the B19 viral proteins
      VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone
      diseases or growth retardation were also analyzed. The sequence of the viral DNA,
      amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus
      was isolated from sera and synovial fluid by adsorption to protein A beads. The
      amount of free virus versus immunocomplexed virus particles was determined by
      quantification of the viral genomes by quantitative PCR. RESULTS: Twenty-six of
      the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum
      (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the
      124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six
      patients (62%) had serum IgG against the structural proteins, indicating past
      infection with B19. NS1-specific antibodies were detected in sera from 29
      patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%)
      showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected
      in followup samples of serum and synovial fluid. Sequencing revealed low-degree
      nucleotide variations that are in the range of genotype 1 of parvovirus B19.
      Immunocomplexed virus was present in varying amounts, both in the sera and in the
      synovial fluid samples. CONCLUSION: Parvovirus B19 is frequently found in serum
      or synovial fluid of children with rheumatism. The rate of persistent B19
      infection in these patients is significantly higher than in age-matched controls.

PMID- 12794832
TI  - Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage
      fluid from patients with scleroderma lung disease.
AB  - OBJECTIVE: The leukotrienes are a family of arachidonic acid-derived lipid
      mediators with proinflammatory and profibrotic properties. The aim of this study
      was to analyze the role of leukotriene B(4) (LTB(4)) and LTE(4) in the
      pathogenesis of scleroderma lung disease (SLD). METHODS: Nineteen systemic
      sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy
      controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during
      routine bronchoscopy of the right middle lobe in all study subjects. Levels of
      LTB(4) and LTE(4) were measured using enzyme immunoassay kits. RESULTS: Levels of
      LTB(4) and LTE(4) were significantly higher in SSc patients with SLD (251 +/- 170
      pg/ml and 479 +/- 301 pg/ml, respectively), than those in patients without SLD
      (114 +/- 86 and 159 +/- 149 pg/ml) and those in normal controls (86 +/- 49 and
      110 +/- 67 pg/ml). In the total group of patients with SSc, levels of both
      leukotrienes correlated positively with the total number of cells in the BAL
      fluid and correlated negatively with the forced vital capacity. After intravenous
      pulse therapy with cyclophosphamide in 6 patients, there was a significant
      reduction in the concentration of LTB(4) (from 380 +/- 196 pg/ml to 155 +/- 123
      pg/ml) but no significant difference in the levels of LTE(4) (from 697 +/- 325
      pg/ml to 418 +/- 140 pg/ml). CONCLUSION: Our findings show that LTB(4) and LTE(4)
      levels are elevated in SSc patients with SLD and correlate with parameters of
      inflammation in the lungs. These results indicate that leukotrienes may
      contribute to the pathogenesis of SLD and may represent a new therapeutic target.

PMID- 12794833
TI  - Anti-c-Mpl (thrombopoietin receptor) autoantibody-induced amegakaryocytic
      thrombocytopenia in a patient with systemic sclerosis.
AB  - Amegakaryocytic thrombocytopenia (AMT) associated with systemic sclerosis (SSc)
      has been described in several case reports, but the underlying mechanisms have
      not been identified. Here we describe a rare case of SSc accompanied by
      thrombocytopenia and megakaryocytic hypoplasia, in which autoantibody against
      thrombopoietin receptor (c-Mpl) was detected. A 61-year-old woman with limited
      SSc was admitted to our hospital because of severe thrombocytopenia (platelet
      count 0.2 x 10(4)/mm(3)) with gingival bleeding. Her bone marrow was hypocellular
      with absent megakaryocytes, consistent with AMT. Treatment with corticosteroids
      and intravenous immunoglobulin infusions resulted in an increased platelet count,
      and she sustained a remission over a 1-year period, with a platelet count
      averaging 10.0 x 10(4)/mm(3). Her serum was strongly positive for anti-c-Mpl
      antibody, and IgG fraction purified from her serum inhibited thrombopoietin
      dependent cell proliferation in vitro. Our case report suggests that AMT in
      patients with SSc could be mediated by the anti-c-Mpl antibody, which
      functionally blocks an interaction between thrombopoietin and c-Mpl.

PMID- 12794834
TI  - Epidermal growth factor up-regulates expression of transforming growth factor
      beta receptor type II in human dermal fibroblasts by phosphoinositide 3
      kinase/Akt signaling pathway: Resistance to epidermal growth factor stimulation
      in scleroderma fibroblasts.
AB  - OBJECTIVE: Transforming growth factor beta receptors (TGFbetaRs) are known to be
      expressed at high levels in several fibrotic diseases, including systemic
      sclerosis. In the present study, we investigated the mechanism of up-regulation
      of TGFbetaR expression. METHODS: The levels of expression of TGFbetaR type II
      (TGFbetaRII) messenger RNA (mRNA), with or without stimulation by epidermal
      growth factor (EGF), were evaluated by Northern blot analysis, and the protein
      levels were determined by immunoblotting. The transcription activity of the
      TGFbetaRII gene was examined with luciferase assays using the -1670/+35
      TGFbetaRII promoter luciferase construct. RESULTS: EGF up-regulates the
      expression of TGFbetaRII mRNA and protein in human dermal fibroblasts.
      Actinomycin D, an RNA synthesis inhibitor, significantly blocked the EGF-mediated
      up-regulation of TGFbetaRII mRNA expression, whereas cycloheximide, a protein
      synthesis inhibitor, did not block this up-regulation. In addition, EGF treatment
      did not significantly affect the TGFbetaRII mRNA half-life. EGF-mediated
      induction of TGFbetaRII expression was inhibited by treatment of fibroblasts with
      the selective phosphoinositide 3-kinase (PI 3-kinase) inhibitors wortmannin or
      LY294002, and Akt inhibitor also blocked EGF-induced expression of TGFbetaRII. In
      addition, EGF induced TGFbetaRII promoter activity, and this induction was
      significantly blocked by wortmannin, LY294002, or Akt inhibitor. Cotransfection
      with a dominant-negative mutant of p85 (the regulatory component of PI 3-kinase)
      or Akt significantly reduced the induction of TGFbetaRII promoter activity by
      EGF. Moreover, a constitutive active form of p110 (a catalytic component of PI 3
      kinase) induced TGFbetaRII promoter activity. In addition, scleroderma
      fibroblasts expressed increased levels of TGFbetaRII but did not show further up
      regulation of TGFbetaRII expression by EGF. CONCLUSION: These results indicate
      that EGF-mediated induction of TGFbetaRII expression occurs at the transcription
      level, does not require de novo protein synthesis, and involves the PI 3
      kinase/Akt signaling pathway, and that abnormal activation of EGF-mediated
      signaling pathways, including PI 3-kinase or Akt, might play a role in the up
      regulation of TGFbetaRII in scleroderma fibroblasts.

PMID- 12794835
TI  - Six-month results of a double-blind, placebo-controlled trial of etanercept
      treatment in patients with active ankylosing spondylitis.
AB  - OBJECTIVE: There is increasing evidence that tumor necrosis factor alpha
      (TNFalpha) is centrally involved in the pathogenesis of ankylosing spondylitis
      (AS) and other spondylarthritides. This study was designed to investigate the
      efficacy of anti-TNFalpha therapy with etanercept, a 75-kd receptor fusion
      protein, in active AS. METHODS: This multicenter trial had 2 phases: an initial
      placebo-controlled period of 6 weeks' duration and an observational phase lasting
      24 weeks. Thirty patients with active AS were included. They were randomized into
      2 groups, which received either etanercept (25 mg twice weekly) (n = 14) or
      placebo (n = 16) for 6 weeks. Then both groups were treated with etanercept.
      Nonsteroidal antiinflammatory drug (NSAID) treatment could be continued, but
      disease-modifying antirheumatic drugs (DMARDs) and steroids had to be withdrawn
      prior to the study. All patients received etanercept for a total of 12 weeks and
      were followed up for at least 24 weeks. The Bath AS Disease Activity Index
      (BASDAI), Bath AS Functional Index, Bath AS Metrology Index, pain level on a
      numeric rating scale, quality of life by the Short Form 36, and C-reactive
      protein (CRP) level were assessed. The primary outcome parameter was a >or=50%
      improvement in the BASDAI. RESULTS: Treatment with etanercept resulted in at
      least a 50% regression of disease activity in 57% of these patients at week 6,
      versus 6% of the placebo-treated patients (P = 0.004). After the placebo-treated
      patients switched to etanercept, 56% improved. The mean +/- SD BASDAI improved
      from 6.5 +/- 1.2 at baseline to 3.5 +/- 1.9 at week 6 in the etanercept group,
      with no improvement in the placebo group (P = 0.003 between groups). Similarly,
      pain, function, mobility, and quality of life improved with etanercept but not
      with placebo at week 6 (P < 0.05). Mean CRP levels decreased significantly with
      etanercept but not with placebo (P = 0.001). There was ongoing improvement in all
      parameters in both groups until week 12 and week 18, respectively (i.e.,
      throughout the period of etanercept treatment). Disease relapses occurred a mean
      +/- SD of 6.2 +/- 3.0 weeks after cessation of etanercept. No severe adverse
      events, including major infections, were observed during the trial. CONCLUSION:
      This study shows that on a short-term basis (3 months), treatment with etanercept
      is clearly efficacious in patients with active AS who are receiving NSAID therapy
      but not DMARDs or steroids. After cessation of therapy, almost all patients
      experienced a relapse within a few weeks. Thus, it seems probable that etanercept
      must be administered continuously in most AS patients to achieve permanent
      inhibition of the inflammatory process.

PMID- 12794836
TI  - Increased perivascular synovial membrane expression of myeloid-related proteins
      in psoriatic arthritis.
AB  - OBJECTIVE: To analyze S-100 protein expression, in the form of myeloid-related
      protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis
      (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy
      (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP
      antigen expression in PsA patients. METHODS: Serum, synovial fluid (SF), and
      synovium (taken at arthroscopy) samples were obtained from PsA (before and after
      MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and
      SF were measured by enzyme-linked immunosorbent assay. Expression of MRP8, MRP14,
      and MRP8/MRP14 in synovium was determined by immunohistochemistry. RESULTS: MRP8,
      MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA,
      RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed
      significantly higher MRP8/MRP14 levels in SF (mean +/- SD 15310 +/- 16999 ng/ml
      [median 11400]) than in serum (908 +/- 679 ng/ml [median 695]) (P = 0.0001).
      MRP8/MRP14 levels in serum correlated with systemic parameters of disease
      activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C-reactive
      protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with
      local parameters of disease activity (white blood cell count r = 0.45, P = 0.01;
      acute-phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was
      significantly higher in the synovial sublining layer (SLL) of PsA patients
      compared with RA and SpA patients. MRP antigens were predominantly expressed in
      perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP
      expression in serum and synovium from PsA patients was significantly reduced.
      Serum levels of MRP were more sensitive to the effects of MTX than were the ESR,
      CRP, or clinical joint scores. CONCLUSION: MRP levels in serum and SF correlate
      with local and systemic inflammation and are equally increased in PsA, RA, and
      SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of
      PsA patients is increased, particularly in perivascular regions, compared with
      that in RA and SpA patients, suggesting a central role of MRP proteins in
      transendothelial migration of leukocytes in PsA. Moreover, MRP expression is
      reduced following MTX treatment. MRP proteins may represent a novel therapeutic
      target in inflammatory arthritis.

PMID- 12794837
TI  - Association of widespread body pain with an increased risk of cancer and reduced
      cancer survival: a prospective, population-based study.
AB  - OBJECTIVE: To determine whether reported widespread body pain is related to an
      increased incidence of cancer and/or reduced survival from cancer, since our
      previous population surveys have demonstrated a relationship between widespread
      body pain and a subsequent 2-fold increase in mortality from cancer over an 8
      year period. METHODS: A total of 6565 subjects in Northwest England participated
      in 2 health surveys during 1991-1992. The subjects were classified according to
      their reported pain status (no pain, regional pain, and widespread pain), and
      were subsequently followed up prospectively until December 31, 1999. During
      followup, information was collected on incidence of cancer and survival rates
      among those developing cancer. Associations between the original pain status and
      development of cancer and cancer survival were expressed as the incidence rate
      ratio (IRR) and mortality rate ratio (MRR), respectively. All analyses were
      adjusted for age, sex, and study location, the latter being a proxy measure of
      socioeconomic status. RESULTS: Among the study population, 6331 had never been
      diagnosed with cancer at the time of participation in the survey. Of these
      subjects, 956 (15%) were classified as having widespread pain, 3061 (48%) as
      having regional pain, and 2314 (37%) as having no pain. There were a total of 395
      first malignancies recorded during followup. In comparison with subjects
      reporting no pain, those with regional pain (IRR 1.19, 95% confidence interval
      [95% CI] 0.94-1.50) and widespread pain (IRR 1.61, 95% CI 1.21-2.13) experienced
      an excess incidence of cancer during the followup period. The increased incidence
      among subjects previously reporting widespread pain was related, most strongly,
      to breast cancer (IRR 3.67, 95% CI 1.39-9.68), but there were also cancers of the
      prostate (IRR 3.46, 95% CI 1.25-9.59), large bowel (IRR 2.35, 95% CI 0.96-5.77),
      and lung (IRR 2.04, 95% CI 0.96-4.34). Subjects reporting widespread pain who
      subsequently developed cancer, in comparison with those previously reporting no
      pain, had an increased risk of death (MRR 1.82, 95% CI 1.18-2.80). This decreased
      survival was highest among subjects with cancers of the breast and prostate,
      although the effects on site-specific survival were nonsignificant. CONCLUSION:
      This study has demonstrated that widespread pain reported in population surveys
      is associated with a substantial subsequent increased incidence of cancer and
      reduced cancer survival. At present there are no satisfactory biologic
      explanations for this observation, although several possible leads have been
      identified.

PMID- 12794838
TI  - High mobility group box chromosomal protein 1, a DNA binding cytokine, induces
      arthritis.
AB  - OBJECTIVE: To examine the potential role of high mobility group box chromosomal
      protein 1 (HMGB-1) in the pathogenesis of arthritis. METHODS: Mice were injected
      intraarticularly with 1 microg or 5 microg of HMGB-1. Joints were dissected on
      days 4, 7, and 28 after injection and were evaluated histopathologically and
      immunohistochemically. To investigate the importance of different white blood
      cell populations for the development of arthritis, in vivo cell depletion
      procedures were performed. In addition, spleen cells were cultured in the
      presence of HMGB-1, and nuclear factor kappaB (NF-kappaB) activation was detected
      by electrophoretic mobility shift assay. RESULTS: Injection of recombinant HMGB-1
      (rHMGB-1) into different mouse strains resulted in an overall frequency of
      arthritis in 80% of the animals. The inflammation was characterized by mild to
      moderate synovitis and lasted for at least 28 days. The majority of cells found
      in the inflamed synovium were Mac-1+ macrophages, whereas only a few CD4+
      lymphocytes were detected. Pannus formation was observed in some cases 7 and 28
      days after HMGB-1 injection. No significant differences were found with respect
      to incidence and severity of arthritis between mice depleted of monocytes,
      granulocytes, or lacking T/B lymphocytes. However, combined removal of monocytes
      and neutrophils resulted in a 43% lower incidence of arthritis. Mice rendered
      deficient in the interleukin-1 (IL-1) receptor did not develop inflammation upon
      challenge with HMGB-1. In vitro data corroborate this finding, showing that rHMGB
      1 activated NF-kappaB, a major pathway leading to IL-1 production. CONCLUSION:
      Our results indicate that HMGB-1 is not a mere expression of inflammatory
      responses, but on its own, it triggers joint inflammation by activating
      macrophages and inducing production of IL-1 via NF-kappaB activation.

PMID- 12794839
TI  - Influence of stimulatory and suppressive DNA motifs on host susceptibility to
      inflammatory arthritis.
AB  - OBJECTIVE: To examine whether systemic administration of immunostimulatory and
      immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to
      inflammatory arthritis. METHODS: Normal BALB/c mice were treated systemically
      with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG
      DNA. The onset and magnitude of the resulting inflammatory response was
      monitored. RESULTS: Systemic delivery of CpG ODNs significantly increased
      susceptibility to local inflammation, whereas systemic treatment with suppressive
      ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating
      host sensitivity to arthritis. These cells were the dominant source of tumor
      necrosis factor alpha production in CpG-stimulated animals and transferred
      resistance to arthritis from mice treated with suppressive ODNs. CONCLUSION:
      Systemic exposure to immunostimulatory and immunosuppressive DNA influences host
      susceptibility to local inflammatory challenge. Current findings raise the
      possibility that suppressive ODNs may be useful in the prevention/treatment of
      proinflammatory diseases.

PMID- 12794840
TI  - Sex effect on clinical and immunologic quantitative trait loci in a murine model
      of rheumatoid arthritis.
AB  - OBJECTIVE: To explore the effect of sex on clinical and immunologic traits in
      major histocompatibility complex-matched (H-2d) F(2) hybrid mice with
      proteoglycan (PG)-induced arthritis and to identify how the quantitative trait
      locus (QTL) on the X chromosome influences the onset QTL of another chromosome.
      METHODS: (BALB/c x DBA/2)F(2) hybrid mice were immunized with cartilage PG, and a
      genome-wide linkage analysis was performed using >200 simple sequence-length
      polymorphic markers. The major clinical traits (susceptibility, onset, and
      severity) were assessed, and PG-specific T and B cell responses, and the
      production of proinflammatory and antiinflammatory cytokines (tumor necrosis
      factor alpha, interleukin-1 [IL-1], IL-6, interferon-gamma, IL-4, IL-10, and IL
      12) were measured in 133 arthritic and 426 nonarthritic female and male F(2)
      hybrid mice. The major clinical and immunologic traits were linked to genetic
      loci, and potential linkages among these QTLs and the effect of sex were
      analyzed. RESULTS: Thirteen QTLs reported in previous studies were confirmed.
      Binary traits (susceptibility to arthritis) and disease onset were female
      specific and were identified on chromosomes 3, 7, 10, 11, 13, and X. QTLs for
      disease severity were mostly male specific and were located on chromosomes 1, 4,
      5, 8, 14, 15, and 19. In addition, we identified 4 new QTLs for the onset of
      arthritis on chromosomes 3, 4, and 11, and 1 new QTL for severity on chromosome
      14; all showed a strong gender association. A locus on the X chromosome
      interacted with a QTL on chromosome 10, and these 2 loci together seemed to
      control disease incidence and onset. Most of the clinical traits (QTLs) shared
      common regions with the immunologic traits and frequently showed a locus-locus
      interaction. CONCLUSION: Numerous immunologic QTLs overlap with clinical QTLs,
      thus providing information about possible mechanisms underlying QTL function.
      Disease susceptibility and onset showed predominant linkage with the female sex,
      under the control of a QTL on the X chromosome, while the severity QTLs were more
      strongly linked to the male sex.

PMID- 12794841
TI  - Blockade of parathyroid hormone-related protein prevents joint destruction and
      granuloma formation in streptococcal cell wall-induced arthritis.
AB  - OBJECTIVE: To determine whether parathyroid hormone-related protein (PTHrP), an
      interleukin-1beta-inducible, bone-resorbing peptide that is produced in
      increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role
      in the pathophysiology of joint destruction in RA. METHODS: PTHrP expression and
      the effect of PTHrP 1-34 neutralizing antibody on disease progression were tested
      in streptococcal cell wall (SCW)-induced arthritis, an animal model of RA.
      RESULTS: As has been reported in RA, while serum levels of PTHrP did not change
      during SCW-induced arthritis, PTHrP expression dramatically increased in the
      arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control
      antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP
      antibody significantly inhibited SCW-induced joint destruction, as measured by
      its ability to block increases in serum pyridinoline (a marker of cartilage and
      bone destruction), erosion of articular cartilage, decreases in femoral bone
      mineral density, and increases in the numbers of osteoclasts in eroded bone.
      Unexpectedly, granuloma formation at sites of SCW deposition in the liver and
      spleen was also inhibited by PTHrP antibody, an effect associated with
      significant decreases in the tissue influx of PTH/PTHrP receptor-positive
      neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was
      stimulated by PTHrP 1-34. CONCLUSION: These findings suggest that PTHrP,
      consistent with its previously described osteolytic effects in metastatic bone
      disease, can also be an important mediator of joint destruction in inflammatory
      bone disorders, such as RA. Moreover, this study reveals heretofore unknown
      effects of PTHrP peptides on neutrophil function that could have important
      implications in the pathogenesis of inflammatory granulomatous disorders.

PMID- 12794842
TI  - Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in
      adult rats with collagen-induced arthritis.
AB  - OBJECTIVE: To study the effect of minodronic acid (ONO-5920) on bone loss and
      arthritis in rats with collagen-induced arthritis (CIA) treated according to 2
      different schedules. METHODS: Four groups of female Sprague-Dawley rats (7 months
      old) were studied: rats without CIA treated with vehicle (controls), CIA rats
      treated with vehicle (CIA-V), CIA rats treated therapeutically with minodronic
      acid (CIA-T), and CIA rats treated prophylactically with minodronic acid (CIA-P).
      Minodronic acid was administered orally at 0.2 mg/kg 3 times a week, beginning 2
      weeks after initial sensitization in the CIA-T rats and beginning the day after
      initial sensitization in the CIA-P rats. Bone mineral density (BMD) was measured
      by peripheral quantitative computed tomography in the proximal metaphysis and
      diaphysis of the tibia every 2 weeks until week 8, when the rats were killed. The
      BMD and bone microstructure of the excised femur were evaluated by dual x-ray
      absorptiometry and microfocal computed tomography, respectively. Histomorphometry
      of the proximal tibia was also performed. RESULTS: In CIA-P rats, the incidence
      of arthritis and the severity of posterior limb swelling were reduced early after
      sensitization, and the decrease in BMD was prevented throughout the observation
      period. Bone and joint destruction evaluated by radiography of the foot was
      reduced in CIA-P rats. The eroded surface was reduced and the microstructure was
      maintained in CIA-P rats compared with CIA-V rats. The mineral apposition and
      bone formation rates were not reduced in the CIA-P rats. In CIA-T rats, however,
      the inflammation was not suppressed and the inhibitory effect on bone loss was
      smaller than that in CIA-P rats. CONCLUSION: Minodronic acid suppressed the
      decrease in BMD and the deterioration of the bone microstructure caused by
      arthritis. Prophylactic administration of minodronic acid had a preventive effect
      on arthritis at the early stage, although not throughout the observation period.

PMID- 12794843
TI  - Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced
      musculoskeletal side effects in rats.
AB  - OBJECTIVE: To characterize the clinical and histopathologic changes in a rat
      model of broad-spectrum matrix metalloproteinase (MMP)-induced musculoskeletal
      syndrome (MSS), and to facilitate research into the causes and treatments of MSS
      in humans. METHODS: Male Lewis rats weighing 150-180 gm were administered 10-30
      mg of the broad-spectrum MMP inhibitor marimastat over a 2-week period via
      surgically implanted subcutaneous osmotic pumps. The animals were monitored and
      scored for the onset and severity of MSS, using clinical and histologic
      parameters. RESULTS: Marimastat-treated rats exhibited various clinical signs,
      including compromised ability to rest on their hind feet, high-stepping gait,
      reluctance or inability to move, and hind paw swelling. Histologically,
      marimastat-treated rat joints were characterized by soft tissue and bone changes,
      such as increased epiphyseal growth plate, synovial hyperplasia, and increased
      cellularity in the joint capsule and extracapsular ligaments. The severity of
      MSS, as judged by clinical criteria (2 blinded observers using 3 clinical
      parameters), paw volume, and histologic score, was nearly identical. The observed
      changes were indistinguishable from those reported for primate models and mimic
      MSS in humans. CONCLUSION: This simple and sensitive model of MSS is an
      attractive alternative for studying the pathology of MSS.

PMID- 12794845
TI  - Female sex increases risk for rheumatoid arthritis only in individuals encoding
      low-risk HLA-DRB1 alleles.

PMID- 12794844
TI  - Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced
      by adenoviral gene transfer of oncostatin M: a comparative study in gene
      deficient mice.
AB  - OBJECTIVE: To investigate the involvement of proinflammatory and destructive
      mediators in oncostatin M (OSM)-induced joint pathology, using gene-deficient
      mice. METHODS: An adenoviral vector expressing murine OSM was injected into the
      joints of naive wild-type mice and mice deficient for interleukin-1 (IL-1), IL-6,
      tumor necrosis factor alpha (TNFalpha), or inducible nitric oxide synthase
      (iNOS). Reverse transcription-polymerase chain reaction was used to study gene
      expression. Inflammation and cartilage proteoglycan (PG) depletion were assessed
      by histology. OSM and IL-1 levels in synovial fluid from patients with juvenile
      idiopathic arthritis (JIA) were measured by enzyme-linked immunosorbent assay.
      RESULTS: Adenoviral expression of murine OSM led to joint inflammation, bone
      apposition, chondrophyte formation, articular cartilage PG depletion, and VDIPEN
      neoepitope expression in wild-type mice. A unique and consistent observation was
      the focal PG depletion and disorganization of the growth plate cartilage during
      the first week of inflammation. Synovial IL-1beta, IL-6, TNFalpha, and iNOS gene
      expression was strongly induced. Of these factors, only deficiency in IL-1
      markedly reduced inflammation and PG depletion and completely prevented growth
      plate damage. In addition, this is the first study in which OSM was detected in
      JIA synovial fluid. Most samples were also IL-1beta positive. CONCLUSION: IL-1,
      but not IL-6, TNFalpha, or iNOS, plays an important role in joint disease induced
      by intraarticular gene transfer of OSM in mice. The effect of OSM on murine
      connective tissue and the presence of OSM in human synovial fluid make
      involvement of OSM in human arthropathies very likely.

PMID- 12794847
TI  - Report of an additional case of anti-tumor necrosis factor therapy and Listeria
      monocytogenes infection: comment on the letter by Gluck et al.

PMID- 12794848
TI  - New American Academy of Ophthalmology recommendations on screening for
      hydroxychloroquine retinopathy.

PMID- 12794850
TI  - Pseudoscleroderma associated with transforming growth factor beta1-producing
      advanced gastric carcinoma: comment on the article by Varga.

PMID- 12794852
TI  - Emerging clinical spectrum of tumor necrosis factor receptor-associated periodic
      syndrome: comment on the articles by Hull et al and Dode et al.

PMID- 12794854
TI  - Clinical images: Tumoral calcinosis associated with sarcoidosis.

PMID- 12794857
TI  - Chemical neuroimmunology: health in a nutshell bidirectional communication
      between immune and stress (limbic-hypothalamic-pituitary-adrenal) systems.
AB  - Stress is a ubiquitous and pervasive part of modern life that is frequently
      blamed for causing a plethora of diseases and other discomforting medical
      conditions. All higher organisms, including humans, experience stress in the form
      of a wide variety of stressors that range from environmental pollutants and drugs
      to traumatic events or self-induced trauma. Stressors registered by the central
      nervous system (CNS) generate physiological stress responses in the body
      (periphery) by means of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis.
      This LHPA axis operates through the use of chemical messengers such as the stress
      hormones corticotropin-releasing hormone (CRH) and glucocorticoids (GCs). Under
      conditions of frequent exposure to acute stress and/or chronic, long-term
      exposure to stress, the LHPA axis becomes dysfunctional and in the process
      frequently overproduces both CRH and GCs, which results in many mild to severely
      toxic side effects. Bidirectional communication between the LHPA axis and
      immune/inflammatory systems can dramatically potentiate these side effects and
      create environments in the CNS and periphery ripe for the triggering and/or
      promotion of tissue degeneration and disease. This review aims to present as far
      as possible a molecular view of the processes involved so as to provide a bridge
      from the diffuse range of studies on molecular structure and receptor
      interactions to the burgeoning biological and medical literature that describes
      the empirical interplay between stress and disease. We hope that our review of
      this fast-growing field, which we christen chemical neuroimmunology, will give a
      clear indication of the striking range and depth of current molecular, cellular
      and medical evidence linking stress hormones to degeneration and disease. In so
      doing, we hope to provide encouragement for others to become interested in this
      critical and far-reaching field of research, which is very much at the heart of
      many important disease processes and very much a critical part of the crucial
      interface between chemistry and biology.

PMID- 12794858
TI  - A molecular mechanism of enantiorecognition of tertiary alcohols by
      carboxylesterases.
AB  - Carboxylesterases containing the sequence motif GGGX catalyze the hydrolysis of
      esters of chiral tertiary alcohols, albeit with only low to moderate
      enantioselectivity, for three model substrates (linalyl acetate, methyl-1-pentin
      1-yl acetate, 2-phenyl-3-butin-2-yl acetate). In order to understand the
      molecular mechanism of enantiorecognition and to improve enantioselectivity for
      this interesting substrate class, the interaction of both enantiomers with the
      substrate binding sites of acetylcholinesterases and p-nitrobenzyl esterase from
      Bacillus subtilis was modeled and correlated to experimental enantioselectivity.
      For all substrate-enzyme pairs, enantiopreference and ranking by
      enantioselectivity could be predicted by the model. In p-nitrobenzyl esterase,
      one of the key residues in determining enantioselectivity was G105: exchange of
      this amino acid for an alanine residue led to a sixfold increase of
      enantioselectivity (E = 19) towards 2-phenyl-3-butin-2-yl acetate. However, the
      effect of this mutation is specific: the same mutant had the opposite
      enantiopreference towards the substrate linalyl acetate. Thus, depending on the
      substrate structure, the same mutant has either increased enantioselectivity or
      opposite enantiopreference compared to the wild-type enzyme.

PMID- 12794859
TI  - Synthesis, receptor binding, molecular modeling, and proliferative assays of a
      series of 17alpha-arylestradiols.
AB  - A series of new derivatives of estradiol substituted at position 17alpha by
      various aryls has been synthesized. This was made possible by efficient
      activation methods for the addition of aryllithiums to the carbonyl group at
      position 17 of estrone by using tetramethylethylenediamine (TMEDA) or BF3 x OEt2.
      Their relative binding affinity (RBA) for the alpha and the beta forms of the
      estrogen receptor (ER) have been measured. All except one of the compounds
      synthesized had an RBA value of around 10 % which indicates a level of tolerance
      towards the bulky substituent at position 17. The lipophilicity values measured
      for these compounds are higher than that found for estradiol (E2). A study of
      their proliferative/antiproliferative effects was carried out on hormone
      dependent (MCF7) and hormone-independent (MDA-MB231) breast cancer cell lines. It
      is interesting to note that all the compounds are estrogenic. The possibility of
      easily attaching an iodine at the end of a phenyl spacer opens up a route to new
      radiopharmaceuticals for use in radioimaging.

PMID- 12794860
TI  - Synthesis of cytidine ribonucleotides by stepwise assembly of the heterocycle on
      a sugar phosphate.
AB  - Although various syntheses of the nucleic acid bases exist and ribose is a
      product of the formose reaction, no prebiotically plausible methods for attaching
      pyrimidine bases to ribose to give nucleosides have been described. Kinetic and
      thermodynamic factors are thought to mitigate against such condensation reactions
      in aqueous solution. This inability to produce pyrimidine nucleosides and hence
      nucleotides is a major stumbling block of the "RNA World" hypothesis and has led
      to suggestions of alternative nucleic acids as evolutionary precursors to RNA.
      Here, we show that a process in which the base is assembled in stages on a sugar
      phosphate can produce cytidine nucleotides. The sequential action of cyanamide
      and cyanoacetylene on arabinose-3-phosphate produces cytidine-2',3'
      cyclophosphate and arabinocytidine-3'-phosphate.

PMID- 12794862
TI  - One-pot TiO2-catalyzed synthesis of nucleic bases and acyclonucleosides from
      formamide: implications for the origin of life.
AB  - A novel one-pot TiO2-catalyzed synthesis of nucleobases and acyclonucleosides
      from formamide is reported. Since formamide can be formed under prebiotic
      conditions, these reactions have implications for the origin of life. While a
      number of purine derivatives have been found as products of non-TiO2-catalyzed
      reactions, important compounds that would not otherwise occur (namely, thymine, 5
      hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by
      TiO2-catalyzed reactions. Moreover, TiO2 selectively affects the rates of
      degradation of nucleobases, as single units and when embedded in polynucleotides.

PMID- 12794861
TI  - Simplified synthetic TMC-95A/B analogues retain the potency of proteasome
      inhibitory activity.
AB  - The proteasome regulates diverse intracellular processes, including cell-cycle
      progression, antigen presentation, and inflammatory response. Selective
      inhibitors of the proteasome have great therapeutic potential for the treatment
      of cancer and inflammatory disorders. Natural cyclic peptides TMC-95A and B
      represent a new class of noncovalent, selective proteasome inhibitors. To explore
      the structure-activity relationship of this class of proteasome inhibitors, a
      series of TMC-95A/B analogues were prepared and analyzed. We found that the
      unique enamide functionality at the C8 position of TMC-95s can be replaced with a
      simple allylamide. The asymmetric center at C36 that distinguishes TMC-95A from
      TMC-95B but which necessitates a complicated separation of the two compounds can
      be eliminated. Therefore, these findings could lead to the development of more
      accessible simple analogues as potential therapeutic agents.

PMID- 12794863
TI  - Mollusk shell acidic proteins: in search of individual functions.
AB  - Acidic proteins play a major role in the biomineralization process. These
      proteins are generally thought to control mineral formation and growth. Thus,
      characterization of individual acidic proteins is important as a first step
      toward linking function to individual proteins, which is our ultimate goal. In
      order to characterize the protein(s) responsible for the assemblage of
      biominerals, a new gel electrophoresis fixing and staining protocol was developed
      and many, if not all of the acidic proteins were visualized on the gel for the
      first time. In an in vitro assay we show that proteins extracted from an
      aragonitic shell layer induce the formation of amorphous calcium carbonate prior
      to its transformation into the aragonitic crystalline form. This study removes
      some major obstacles in the characterization of acidic proteins and sheds more
      light on the functions of these proteins in the biomineralization process.

PMID- 12794864
TI  - In vivo chaperone-assisted folding of alpha-1,6-fucosyltransferase from Rhizobium
      sp.

PMID- 12794865
TI  - Selective protein degradation by ligand-targeted enzymes: towards the creation of
      catalytic antagonists.

PMID- 12794866
TI  - Binding and catalysis: a thermodynamic study on a catalytic antibody system.

PMID- 12794868
TI  - Cold-spray ionization mass spectrometry: principle and applications.
AB  - A direct solution analysis method, cold-spray ionization (CSI) mass spectrometry
      (MS), a variant of electrospray (ESI) MS operating at low temperature (ca -80 to
      10 degrees C), allows the facile and precise characterization of labile organic
      species, especially those in which non-covalent bonding interactions are
      prominent. We applied this method to investigations of the solution structures of
      many labile organic species, including unstable reagents and reaction
      intermediates, asymmetric catalysts, supramolecules and even primary
      biomolecules. Remarkable analytical results were obtained for highly ordered
      supramolecules using the CSI method. Whereas conventional ESI is not applicable
      to these compounds because of their instability to heat and/or air, CSI affords
      multiply charged molecular ions with many solvent molecules attached.
      Investigation of the constitution of Grignard reagents in solution is extremely
      challenging, but CSI-MS allowed us to identify one of the key structures in THF
      solution. Recently, this method was adopted for investigations of the solution
      structures of primary biomolecules such as nucleosides, amino acids, sugars and
      lipids, revealing singly charged Na(+) adducts of large clusters (chain
      structures), presumably linked by non-covalent interactions, including hydrogen
      bonding and/or hydrophobic interactions. The principle of the CSI method and
      applications of the method to a wide variety of labile organic species and
      primary biomolecules in solution are described.

PMID- 12794869
TI  - Influence of response factors on determining equilibrium association constants of
      non-covalent complexes by electrospray ionization mass spectrometry.
AB  - A method for determining the equilibrium association constant of a complexation
      reaction A + B left harpoon over right harpoon AB by electrospray ionization mass
      spectrometry is described. The method consists in measuring the relative
      intensities of the peaks corresponding to A and to AB in equimolar A-B solutions
      at different concentrations C(0). The results are fitted by a non-linear least
      squares procedure, with the two variable parameters being the equilibrium
      association constant K(a) and a factor R, defined by I(AB)/I(A) = R x [AB]/[A].
      The factor R is the ratio between the response factors of AB and A, and corrects
      for the relative electrospray responses of the complex and the free substrate A,
      mass discrimination of instrumental origin and/or moderate in-source
      dissociation. The method is illustrated with the following two systems: complexes
      between a double-stranded 12-base pair oligonucleotide and minor groove binders,
      and cyclodextrin complexes with alpha,omega-dicarboxylic acids. For the
      oligonucleotide complexes, it is found that the response of the complex is not
      dramatically different to the response of the free oligonucleotide duplex, as the
      double helix conformation is disturbed by the drug only to a minor extent. In the
      case of cyclodextrin complexes, these complexes were found to have a much higher
      response than free cyclodextrin. This may be due to the fact that cyclodextrin is
      neutral in solution, whereas the complex is charged, but it can also stem from
      the fact that a significant proportion of the complex is in a non-inclusion
      geometry. The present method requires the exact determination of the
      concentrations of the reactants and is applicable to 1 : 1 complexes.

PMID- 12794870
TI  - Monitoring of unfolding of metallo-proteins by electrospray ionization mass
      spectrometry.
AB  - An electrospray ionisation (ESI) mass spectrometric method for the determination
      of the equilibrium constant and free energy (DeltaG) of protein unfolding was
      used to monitor the denaturation process at different pH of three metallo
      proteins, i.e. wild-type copper azurin, zinc azurin and wild-type amicyanin. The
      time course of the unfolding process was followed by dissolving the proteins
      under denaturing conditions (methanol-water (1 : 1, v/v)) at different pH (2.5,
      3.0, 3.5) and recording ESI spectra at time intervals. The spectra showed two
      series of peaks, corresponding to the native holo-protein and the unfolded apo
      protein. From the intensity ratio of these two series of peaks at increasing time
      and at equilibrium, the equilibrium constants for the unfolding process for the
      three proteins could be determined. From these equilibrium constants a DeltaG
      degrees derivation was attempted. The DeltaG degrees values obtained decrease
      with decrease in pH, in agreement with the expected reduction of conformational
      stability of proteins at lower pH. The results obtained confirm that ESI-MS can
      be used for monitoring of unfolding process and to derive quantitative
      thermodynamic data.

PMID- 12794871
TI  - Relative binding strength of terpyridine model complexes under matrix-assisted
      laser desorption/ionization mass spectrometry conditions.
AB  - The relative binding strength of a series of terpyridine metal complexes of the
      type [M(II)L(2)](+) was investigated by using variable laser intensities in
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS). A model terpyridine ligand, 4'-(1,4,7-trioxa-octyl)-2,2':6',2"
      terpyridine, was prepared and complexed with a series of transition metal ions
      including cadmium, cobalt, copper, iron, manganese, nickel and ruthenium. The
      relative binding strength of these complexes can be obtained by measuring MALDI
      mass spectra of the prepared compounds at different laser intensities. The ratio
      of the signal intensities belonging to the ligand [LH](+) and the complex
      [ML(2)](+) ([LH](+) /[ML(2)](+)) depends on the laser intensity utilized for the
      spectrum acquisition. By considering an [LH](+)/[ML(2)](+) ratio > 10 as the
      point of complete complex dissociation, it is possible to establish a row of
      complex stabilities depending on the kind of metal ion.

PMID- 12794872
TI  - Low-temperature SIMS mass spectra of diethyl ether.
AB  - For the first time a secondary ion mass spectrum of diethyl ether was obtained at
      low temperature. The spectrum recording became possible by carefully selecting
      the range of experimental conditions for the production of a cluster-type
      spectrum. This range is specified by the threshold for spectrum appearance above
      the melting temperature of the frozen sample and a fairly short time span of
      existence of the liquid estimated as only a few minutes. The latter necessitates
      rather rapid spectrum detection. In practice, about 1 min was available for
      recording of the cluster-type spectra. The secondary emission mass spectrum of
      diethyl ether appeared to be rich in peaks: along with abundant protonated
      clusters M(n).H(+) (n = 1-12), unusually intense [M(n) - H](+) and weaker M(n)
      (+.) peaks were present accompanied by several sets of fragmented clusters, [M(n)
      - 15](+), [M(n) - 29](+), [M(n) - 27](+), [M(n) - 45](+), and monohydrates,
      M(n).H(2)O.H(+). The analysis of all the peaks showed that the pattern of
      fragment clusters is qualitatively similar to the pattern of fragmentation of the
      diethyl ether molecular ion under high-energy electron impact. The general
      features of the behaviour of diethyl ether under low-temperature mass
      spectrometric conditions were similar to those observed earlier for some other
      organic solvents.

PMID- 12794873
TI  - Volatile polydimethylcyclosiloxanes in the ambient laboratory air identified as
      source of extreme background signals in nanoelectrospray mass spectrometry.
AB  - Polydimethylcyclosiloxanes, an almost ubiquitous air contaminant, can interfere
      with nanoelectrospray analysis. The sensitivity of nanoelectrospray to these
      volatile air contaminants was demonstrated in this study. The intensity of the
      interfering ion signals caused by these compounds can be decreased by changing
      the position of the nanoESI needle and almost completely suppressed by applying a
      flow of pure nitrogen around the needle and the sample cone. The nitrogen flow
      causes a slight shift in charge distribution, but does not influence the
      sensitivity for peptide detection.

PMID- 12794874
TI  - Decomposition of protein nitrosothiolsin matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry.
AB  - The S-nitrosylation of proteins is involved in the trafficking of nitric oxide
      (NO) in intra- and extracellular milieus. To establish a mass spectrometric
      method for identifying this post-translational modification of proteins, a
      synthetic peptide and transthyretin were S-nitrosylated in vitro and analyzed by
      electrospray ionization (ESI) and matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry. The intact molecular ion species of nitrosylated
      compounds was identified in the ESI mass spectrum without elimination of the NO
      group. However, the labile nature of the S-NO bond was evident when the in-source
      fragmentation efficiently generated [M + H - 30](+) ions. The decomposition was
      prominent for multiply charged transthyretin ions with high charge states under
      ordinary ESI conditions, indicating that the application of minimum nozzle
      potentials was essential for delineating the stoichiometry of nitrosylation in
      proteins. With MALDI, the S-NO bond cleavage occurred during the ionization
      process, and the subsequent reduction generated [M + H - 29](+) ions.

PMID- 12794875
TI  - Mass spectrometric characterization of mitochondrial electron transport
      complexes: subunits of the rat heart ubiquinol-cytochrome c reductase.
AB  - Complex III of the mitochondrial electron transport chain, ubiquinol-cytochrome c
      reductase, was isolated by blue native polyacrylamide gel electrophoresis. Ten of
      the 11 polypeptides present in this complex were detected directly by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS) following electroelution of the active complex. Tryptic and chymotryptic
      digestion of the complex permit the identification of specific peptides from all
      of the protein subunits with 70% coverage of the 250 kDa complex. The mass of all
      11 proteins was confirmed by second dimension Tricine sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and elution of the separated
      polypeptides. Additionally, the identity of the core I, core II, cytochrome c and
      the Rieske iron-sulfur protein were confirmed by liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) characterization of the peptides generated by in-gel
      trypsin digestion of the SDS-PAGE separated proteins. The methodology
      demonstrated for analyzing this membrane-bound electron transport complex should
      be applicable to other membrane complexes, particularly the other mitochondrial
      electron transport complexes. The MS analysis of the peptides obtained by in-gel
      digestion of the intact complex permits the simultaneous characterization of the
      native proteins and modifications that contribute to mitochondrial deficits that
      have been implicated as contributing to pathological conditions.

PMID- 12794876
TI  - Fragmentation of dipyridamole and related dipyrimidines by electrospray
      ionization collisional activated decomposition mass spectrometry.
AB  - The coronary vasodilator, co-activator of antitumor compounds and antioxidant
      drug dipyridamole and several of its derivatives were studied by electrospray
      ionization (ESI) combined with collisional activated decomposition (CAD) in both
      positive and negative modes. These compounds produce abundant monocharged ions
      ([M + H](+)) under ESI. Interpretation of the CAD spectra showed that
      fragmentation occurs preferentially in the ethanolamine groups attached at C-2, C
      4, C-6 and C-8. 2-Methoxyethanol is eliminated when ethanolamines are in
      positions C-2/C-6 and 2-aziridinethanol is eliminated from C-4/C-8 ethanolamines.
      The proposed fragmentation schemes were supported by deuterium labeling
      experiments and tandem mass spectrometry.

PMID- 12794877
TI  - Quantitative analysis of ES-285, an investigational marine anticancer drug, in
      human, mouse, rat, and dog plasma using coupled liquid chromatography and tandem
      mass spectrometry.
AB  - A method was developed for the quantitative analysis of the novel anticancer
      agent ES-285 (spisulosine; free base) in human, mouse, rat, and dog plasma using
      high-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry in order to support pre-clinical and clinical studies with the drug.
      Sample preparation was carried out by protein precipitation with acetonitrile,
      containing isotopically labeled (d(3)) ES-285 as internal standard. Aliquots of
      10 micro l of the supernatant were injected directly on to an Inertsil ODS-3
      column (50 x 2.0 mm i.d., 5 micro m). Elution was carried out using methanol-10
      mM ammonium formate (pH 4) in water (80 : 20, v/v) pumped at a flow-rate of 0.2
      ml min(-1) with a run time of 8 min. Multiple reaction monitoring chromatograms
      obtained on an API365 triple-quadrupole mass spectrometer were used for
      quantification. The lower limit of quantitation (LLOQ) was 10 ng ml(-1) in human,
      mouse, rat, and dog plasma and the linear dynamic range extended to 500 ng ml(
      1). A full validation of the method was performed in human plasma, and partial
      validations were performed in mouse, rat and dog plasma. Accuracies and
      precisions were <20% at the LLOQ concentration and <15% for all other
      concentrations in all matrices. ES-285 was stable during all steps of the assay.
      Thus far this method has been used successfully to analyze over 500 samples in
      pre-clinical trials, and will be implemented in the planned clinical phase I
      studies.

PMID- 12794878
TI  - Structural characterization and isomer differentiation of chalcones by
      electrospray ionization tandem mass spectrometry.
AB  - A series of chalcones were characterized by electrospray ionization tandem mass
      spectrometry (MS(n)). Several ionization modes were evaluated, including
      protonation, deprotonation and metal complexation, with metal complexation being
      the most efficient. Collision-activated dissociation (CAD) was used to
      characterize the structures, and losses commonly observed include H(2), H(2)O, CO
      and CO(2), in addition to methyl radicals for the methoxy-containing chalcones.
      CAD of the metal complexes, especially [Co(II) (chalcone-H) 2,2'-bipyridine](+),
      allowed the most effective differentiation of the isomeric chalcones with several
      diagnostic fragment ions appearing upon activation of the metal complexes. MS(n)
      experiments were performed to support identification of some fragment ions and to
      verify the proposed fragmentation pathways. In several cases, MS(n) indicated
      that specific neutral losses occurred by stepwise pathways, such as the neutral
      loss of 44 u as CH3* and HCO*, or CH(4) and CO, in addition to CO(2).

PMID- 12794880
TI  - Unusual loss of neutral molecules on mass spectrometric decomposition of
      protonated and cationized phenoxy--and phenylaminocyclophosphazenes.

PMID- 12794881
TI  - Mass spectrometric behaviour of (E)-1-silyl-2-alkoxyethenes.

PMID- 12794879
TI  - COMPLX: a computer algorithm for the detection of protein-ligand and other
      macromolecular complexes in mass spectra.
AB  - A new algorithm has been designed and tested to identify protein, or any other
      macromolecular, complexes that have been widely reported in mass spectral data.
      The program takes advantage of the appearance of multiply charged ions that are
      common to both electrospray ionization and, to a lesser extent, matrix-assisted
      laser desorption/ionization (MALDI) mass spectra. The algorithm, known as COMPLX
      for the COMposition of Protein-Ligand compleXes, is capable of identifying
      complexes for any protein or macromolecule with a binding partner of molecular
      mass up to 100 000 Da. It does so by identifying ion pairs present in a mass
      spectrum that, when they share a common charge, have an m/z value difference that
      is an integer fraction of a ligand or binding partner molecular mass. Several
      additional criteria must be met in order for the result to be ranked in the
      output file including that all m/z values for ions of the protein or complex have
      progressively lower values as their assigned charge increases, the difference
      between the m/z values for adjacent charge states (z, z + 1) decrease as the
      assigned charge state increases, and the ratio of any two m/z values assigned to
      a protein or complex is equal to the inverse ratio of their charge. The entries
      that satisfy these criteria are then ranked according to the appearance of ions
      in the mass spectrum associated with the binding partner, the length of a
      continuous series of charges across any set of ions for a protein and complex and
      the lowest error recorded for the molecular mass of the ligand or binding
      partner. A diverse range of hypothetical and experimental mass spectral data were
      used to implement and test the program, including those recorded for antibody
      peptide, protein-peptide and protein-heme complexes. Spectra of increasing
      complexity, in terms of the number of ions input, were also successfully analysed
      in which the number of input m/z values far exceeds the few associated with a
      macromolecular complex. Thus the program will be of value in a future goal of
      proteomics, where mass spectrometry already plays a central role, for the direct
      analysis of protein and other associations within biological extracts.

PMID- 12794882
TI  - Current literature in mass spectrometry.

PMID- 12794884
TI  - Unprecedented living olefin polymerization derived from an attractive interaction
      between a ligand and a growing polymer chain.
AB  - Ti complexes incorporating fluorine-containing phenoxy-imine chelate ligands
      (fluorinated Ti-FI catalysts) have been demonstrated to induce an unprecedented
      living polymerization effect with both ethylene and propylene, through an
      attractive interaction between the fluorine atom in the ligand and a beta
      hydrogen atom on the growing polymer chain. With the aid of this attractive
      interaction, highly controlled living ethylene polymerization, highly
      syndiospecific living propylene polymerization, the synthesis of unique block
      copolymers from ethylene and propylene, and the catalytic production of
      monodisperse polyethylene and Zn-terminated polyethylene have been realized. The
      attractive interaction provides a conceptually new strategy for the achievement
      of controlled living olefin polymerization.

PMID- 12794885
TI  - BaP4Te2--a ternary telluride with P-Te bonds and a structural fragment of black
      phosphorus.
AB  - The new telluride BaP(4)Te(2) was synthesized in form of gleaming black needles
      by heating stochiometric mixtures of the elements to 475 degrees C for 100 h. The
      crystal structure was determined by single-crystal Xray methods. BaP(4)Te(2)
      crystallizes orthorhombically, space group Pnma with a=16.486(8), b=6.484(2),
      c=7.076(4) A, and Z=4. A main feature of the so far unknown crystal structure
      type are P(4)Te(2) chains that consist of condensed six-membered rings of
      phosphorus. These strands are equivalent to a structural fragment of black
      phosphorus, in which each of the lateral atoms is connected to a tellurium atom.
      The chains running along [0 1 0] are separated from each other by barium atoms,
      that is, linked through Ba-Te and Ba-P bonds. BaP(4)Te(2) is an electron precise
      compound according to the Zintl concept, and the formula can be split ionically
      as follows: BaP(4)Te(2) identical with Ba(2+)(P(0))(4)(Te(-))(2). The remarkable
      Te-P bonds have been analyzed by electronic structure calculations using the
      electron localization function (ELF) and the crystal orbital Hamiltonian
      population (COHP) methods.

PMID- 12794886
TI  - Structural study of 2,6-bis[(dimethylaminomethyl)phenyl]butyl stannanes:
      nonconventional behaviour of triorganotin(IV) halides.
AB  - The four organotin (IV) compounds ([2,6-bis(dimethylaminomethyl)phenyl](n
      butyl)R(1)R(2)stannane, with R(1)=R(2)=nBu (1), R(1)=nBu, R(2)=Cl (2), R(1)=nBu,
      R(2)=Br (3) and R(1)=R(2)=Br (4)), have been prepared and their structures have
      been investigated in various solvents and at various temperatures (NMR). The
      structures of these compounds in solution are solvent- and temperature-dependent.
      The solid state structures of 2 and 3 were studied using CP/MAS NMR spectroscopy
      and Xray diffraction techniques. The tetraorganotin compound 1 exhibits
      tetrahedral geometry with very weak Sn-N coordination. The dynamic process of Sn
      N bond(s) association/dissociation was observed using low-temperature NMR
      measurements. The tin central atom in 2 and 3 is [4+2]-coordinated in toluene
      solutions and the NMR low-temperature measurements reveal the same dynamic
      behavior as for 1 in this solution, with retention of the covalent halogen-tin
      bond. However, this bond is dissociated in methanol solutions, yielding ionic
      species, where the tin atom is only [3+2]-coordinated, and the halogen atom lies
      outside of the primary coordination sphere of the tin atom. In addition, while
      the same ionic structure as in methanol was found in the whole measured
      temperature range in the chloroform solution of 3, the structure of 2 varies in
      this solvent. In this compound, the covalent Sn-Cl bond (similar structure as in
      toluene solution), which is retained at room temperature in chloroform solution,
      is continuously dissociated with a decrease in temperature, leading to ionic
      bonding (a similar structure as in methanol solution). All the above-mentioned
      processes are reversible in all the solvents and at all temperatures. In the
      solid state, the covalent Sn-Cl bond is observed for 2, while an ionic bond was
      found in 3.

PMID- 12794887
TI  - Preparation, structure, and unique thermal [2+2], [4+2], and [3+2] cycloaddition
      reactions of 4-vinylideneoxazolidin-2-one.
AB  - The terminal allene C(alpha)=C(beta) bonds of 4vinylidene-2-oxazolidinone (2)
      readily undergo [2+2] cycloaddition with a wide variety of terminal alkynes,
      alkenes, and 1,3-dienes irrespective of their electronic nature under strictly
      thermal activation conditions (70-100 degrees C) and provide 3substituted (Z)
      methylenecyclobutenes 6, 3substituted methylenecyclobutanes 7 and 8, and
      3vinylmethylenecyclobutanes 9, respectively, in good to excellent yields. Alkenes
      react with 2 with complete retention of configuration. The [2+2] cycloaddition is
      concluded to proceed via a concerted [(pi(2s)+pi(2s))(allene) + pi(2s)] Huckel
      transition state on the basis of experimental evidences and quantum mechanical
      methods. Some highly polarized enones and nitrile oxide, on the other hand, react
      with 2 selectively at the internal C(4)=C(alpha) double bonds and give spiro
      compounds 10 and 11, respectively. The bent allene bonds (173-176 degrees) and
      the unique reactivity associated with 2 are attributed to a low-lying LUMO
      (C(alpha)=C(beta)) that is substantiated by a through-space sigma*(N-SO(2))
      pi*(C(alpha)=C(beta)) orbital interaction.

PMID- 12794888
TI  - Potassium selective calix[4]semitubes.
AB  - A new class of ionophore consisting of two calix[4]arene units linked through the
      lower rim by two ethylene chains, in combination with propyl ether and phenolic
      functional groups, has been developed. These calix[4]semitube molecules exhibit
      remarkable selectivity and fast complexation kinetics for potassium over all
      Group 1 metal cations. Molecular modelling studies, using structural models
      derived from crystallographic data, suggest the potassium cation is complexed by
      a horizontal, side-on route and not through the calix[4]arene annulus. The length
      of the bridging alkylene chain between the respective calix[4]arenes of the
      semitube structure dictates the strength and selectivity of alkali metal cation
      binding.

PMID- 12794889
TI  - Pd0-catalyzed coupling cyclization reaction of Aryl or 1-alkenyl halides with 1,2
      allenyl ketones: scope and mechanism. An efficient assembly of 2,3,4-, 2,3,5-tri-
      and 2,3,4,5-tetrasubstituted furans.
AB  - Described herein is the Pd(0)-catalyzed coupling cyclization reaction of 1,2
      allenyl ketones with organic halides leading efficiently and conveniently to not
      only 2,3,4- and 2,3,5-trisubstituted furans but also 2,3,4,5-tetrasubstituted
      furans. Furthermore, this method showed high substituent-loading capability and
      tolerance of various substituents. The reactions of 1,2-allenyl ketones 1 e, 1 p,
      1 q, and deuterated [D]1 c were performed for a mechanistic study, which
      demonstrated that instead of an enolization pathway, the reaction may proceed via
      the intermediacy of dienolate palladium and intramolecular nucleophilic attack on
      the pi-allyl palladium intermediate by the carbonyl oxygen.

PMID- 12794890
TI  - Controlling short- and long-range electron transfer processes in molecular dyads
      and triads.
AB  - Novel pi-extended tetrathiafulvalene (exTTF)-based donor acceptor hybrids-dyads
      and triads-have been synthesized following a multistep synthetic procedure.
      Cyclic voltammetry and absorption spectroscopy, conducted in room temperature
      solutions, reveal features that are identical to the sum of the separate donor
      and acceptor moieties. Steady-state and time-resolved photolytic techniques
      confirm that upon photoexcitation of the fullerene chromophore, rapid (1.25 x
      10(10) s(-1)) and efficient (67 %) charge separation leads to long-lived, charge
      separated radical pairs. Typical lifetimes for the dyad ensembles range between
      54 and 460 ns, with the longer values found in more polar solvents. This
      indicates that the dynamics are located in the 'normal region' of the Marcus
      curve. In the triads, subsequent charge shifts transform the adjacent radical
      pair into the distant radical pair, for which we determined lifetimes of up to
      111 micros in DMF-values never previously accomplished in molecular triads. In
      the final charge-separated state, large donor-acceptor separation (center-to
      center distances: approximately 30 A) minimizes the coupling between reduced
      acceptor and oxidized donor. Analysis of the charge recombination kinetics shows
      that a stepwise mechanism accounts for the unusually long lifetimes.

PMID- 12794891
TI  - Palladium(0)-catalyzed intramolecular [2+2+2] alkyne cyclotrimerizations with
      electron-deficient diynes and triynes.
AB  - In the presence of 2.5 mol % of [Pd(2)(dba)(3)] (dba=dibenzylideneacetone) and 5
      mol % of PPh(3), nearly equimolar amounts of dimethyl nona-2,7-diyne-1,9-dioate
      derivatives (diyne diesters) and dialkyl acetylenedicarboxylates were allowed to
      react in toluene at 110 degrees C to afford [2+2+2] cycloadducts in moderate-to
      good yields. Similarly, dimethyl trideca-2,7,12-triyne-1,13-dioate derivatives
      (triyne diesters) were catalytically transformed into phthalic acid ester
      analogues in excellent yields. To gain insight into the mechanism of these
      intramolecular alkyne cyclotrimerizations, stoichiometric reactions of
      [Pd(2)(dba)(3)] with a diyne diester and a triyne diester bearing ether tethers
      were conducted in acetone at room temperature to furnish an oligomeric
      bicyclopalladacyclopentadiene and a Pd(0) triyne complex, respectively. The
      structures of these novel complexes were unequivocally determined by Xray
      structure analysis. The isolated triyne complex was heated at 50 degrees C or
      treated with PPh(3) in acetone at room temperature to afford the arene product.
      Furthermore, the same complex catalyzed the triyne cyclization with or without
      PPh(3).

PMID- 12794892
TI  - Columnar mesomorphism from hemi-disklike metallomesogens derived from 2,6
      bis[3',4',5'-tri(alkoxy)phenyliminomethyl]pyridines (L): crystal and molecular
      structures of [M(L)Cl2] (M=Mn, Ni, Zn).
AB  - Four new series of non-disklike complexes of general formula [MCl(2)(L(n))] based
      upon substituted 2,6-bis(3',4',5'-trialkoxyphenyliminomethyl)pyridine ligands
      (L(n)) and with M=Zn(II), Co(II), Mn(II), and Ni(II) have been prepared and
      examined for liquid crystallinity. A complete analysis of the thermal behavior by
      polarized-light optical microscopy, differential scanning calorimetry, and small
      angle Xray scattering revealed a rich and varied mesomorphism. Moreover, the high
      thermal stability of the compounds leads to rather extended mesomorphic ranges.
      The nature and thermal stability of each mesophase depend on both the length of
      the six terminal alkoxy chains, n (n=8, 10, 12, 14, 16), and on the metal ions.
      As demonstrated by small-angle Xray diffraction experiments, the mesomorphism of
      these complexes is solely of the columnar type. One compound shows an oblique
      columnar phase, while most of them show a hexagonal columnar phase, Col(h), and
      several types of rectangular columnar phase, Col(r). Xray single-crystal
      structures obtained for three methoxy derivatives confirm the 1:1 metal-ligand
      stoichiometry of the complexes, in which the metal is pentacoordinate with a
      distorted, trigonal bipyramidal geometry. The crystalline structures also reveal
      the existence of some columnar organization in the solid state, the columns
      resulting from an alternated stacking of the complexes in one direction. By
      combining these results with those obtained from dilatometry experiments, a model
      for the molecular organization within the mesophases is proposed in which an
      antiparallel arrangement of the metallomesogens is retained in the mesophase.

PMID- 12794893
TI  - Rhodium(I) and rhodium(III) complexes formed by coordination and C-H activation
      of bulky functionalized phosphanes.
AB  - The reaction of [[RhCl(C(8)H(14))(2)](2)] (2) with iPr(2)PCH(2)CH(2)C(6)H(5)
      (L(1)) led, via the isolated dimer [[RhCl(C(8)H(14))(L(1))](2)] (3), to a mixture
      of three products 4 a-c, of which the dinuclear complex [[RhCl(L(1))(2)](2)] (4
      a) was characterized by Xray crystallography. The mixture of 4a-c reacts with CO,
      ethene, and phenylacetylene to give the square-planar compounds trans
      [RhCl(L)(L(1))(2)] (L=CO (5), C(2)H(4) (6), C=CHPh (9)). The corresponding
      allenylidene(chloro) complex trans-[RhCl(=C=C=CPh(2))(L(1))(2)] (11), obtained
      from 4 a-c and HC triple bond CC(OH)Ph(2) via trans
      [RhCl[=C=CHC(OH)Ph(2)](L(1))(2)] (10), could be converted stepwise to the related
      hydroxo, cationic aqua, and cationic acetone derivatives 12-14, respectively.
      Treatment of 2 and [[RhCl(C(2)H(4))(2)](2)] (7) with two equivalents of
      tBu(2)PCH(2)CH(2)C(6)H(5) (L(2)) gave the dimers [[RhCl(C(8)H(14))(L(2))](2)]
      (15) and [[RhCl(C(2)H(4))(L(2))](2)] (16), which both react with L(2) in the
      molar ratio of 1:2 to afford the five-coordinate aryl(hydrido)rhodium(III)
      complex [RhHCl(C(6)H(4)CH(2)CH(2)PtBu(2)-kappa(2)C,P)(L(2))] (17) by C-H
      activation. The course of the reactions of 17 with CO, H(2), PhC triple bond CH,
      HCl, and AgPF(6), leading to the compounds 19-21, 24, and 25 a, respectively,
      indicate that the coordinatively unsaturated isomer of 17 with the supposed
      composition [RhCl(L(2))(2)] is the reactive species. Labeling experiments using
      D(2), DCl, and PhC triple bond CD support this proposal. With either
      [Rh(C(8)H(14))(eta(6)-L(2)-kappaP]PF(6) or [Rh(C(2)H(4))(eta(6)-L(n)-kappaP]PF(6)
      (n=1 and 2) as the starting materials, the corresponding halfsandwich-type
      complexes 27, 28, and 32 were obtained. The nonchelating counterpart of the
      dihydrido compound 32 with the composition [RhH(2)(PiPr(3))(eta(6)
      C(6)H(6))]PF(6) (35) was prepared stepwise from [Rh(C(2)H(4))(PiPr(3))(eta(6)
      C(6)H(6))]PF(6) and H(2) in acetone via the tris(solvato) species
      [RhH(2)(PiPr(3))(acetone)(3)]PF(6) (34) as intermediate. The synthesis of the
      bis(chelate) complex [Rh(eta(4)-C(8)H(12))(C(6)H(5)OCH(2)CH(2)PtBu(2)
      kappa(2)O,P)]BF(4) (39) is also described. Besides 4 a, the compounds 17, 25 a,
      and 39 have been characterized by Xray crystal structure analysis.

PMID- 12794894
TI  - Synthesis, molecular structure, and C-C coupling reactions of
      carbeneruthenium(II) complexes with C5H5Ru(=CRR') and C5Me5Ru(=CRR') as molecular
      units.
AB  - The ethene derivatives [(eta(5)-C(5)R(5))RuX(C(2)H(4))(PPh(3))] with R=H and Me,
      which have been prepared from the eta(3)-allylic compounds [(eta(5)
      C(5)R(5))Ru(eta(3)-2-MeC(3)H(4))(PPh(3))] (1, 2) and acids HX under an ethene
      atmosphere, are excellent starting materials for the synthesis of a series of new
      halfsandwich-type ruthenium(II) complexes. The olefinic ligand is replaced not
      only by CO and pyridine, but also by internal and terminal alkynes to give (for
      X=Cl) alkyne, vinylidene, and allene compounds of the general composition
      [(eta(5)-C(5)R(5))RuCl(L)(PPh(3))] with L=C(2)(CO(2)Me)(2), Me(3)SiC(2)CO(2)Et,
      C=CHCO(2)R, and C(3)H(4). The allenylidene complex [(eta(5)
      C(5)H(5))RuCl(=C=C=CPh(2))(PPh(3))] is directly accessible from 1 (R=H) in two
      steps with the propargylic alcohol HC triple bond CC(OH)Ph(2) as the precursor.
      The reactions of the ethene derivatives [(eta(5)-C(5)H(5))RuX(C(2)H(4))(PPh(3))]
      (X=Cl, CF(3)CO(2)) with diazo compounds RR'CN(2) yield the corresponding carbene
      complexes [(eta(5)-C(5)R(5))RuX(=CRR')(PPh(3))], while with ethyl diazoacetate
      (for X=Cl) the diethyl maleate compound [(eta(5)-C(5)H(5))RuCl[eta(2)-Z
      C(2)H(2)(CO(2)Et)(2)](PPh(3))] is obtained. Halfsandwich-type ruthenium(II)
      complexes [(eta(5)-C(5)R(5))RuCl(=CHR')(PPh(3))] with secondary carbenes as
      ligands, as well as cationic species [(eta(5)-C(5)H(5))Ru(=CPh(2))(L)(PPh(3))]X
      with L=CO and CNtBu and X=AlCl(4) and PF(6), have also been prepared. The neutral
      compounds [(eta(5)-C(5)H(5))RuCl(=CRR')(PPh(3))] react with phenyllithium,
      methyllithium, and the vinyl Grignard reagent CH(2)=CHMgBr by displacement of the
      chloride and subsequent C-C coupling to generate halfsandwich-type ruthenium(II)
      complexes with eta(3)-benzyl, eta(3)-allyl, and substituted olefins as ligands.
      Protolytic cleavage of the metal-allylic bond in [(eta(5)-C(5)H(5))Ru(eta(3)
      CH(2)CHCR(2))(PPh(3))] with acetic acid affords the corresponding olefins
      R(2)C=CHCH(3). The by-product of this process is the acetato derivative [(eta(5)
      C(5)H(5))Ru(kappa(2)-O(2)CCH(3))(PPh(3))], which can be reconverted to the
      carbene complexes [(eta(5)-C(5)H(5))RuCl(=CR(2))(PPh(3))] in a one-pot reaction
      with R(2)CN(2) and Et(3)NHCl.

PMID- 12794895
TI  - Synthesis and fluorescence ion-sensory properties of the first
      dehydropyridoannulene-type cyclophane with enforced exotopic metal ion binding
      sites.
AB  - The new twistophane 4 has been synthesised, which comprises a conjugated
      dehydropyridoannulene-type macrocyclic scaffold with outwardly projecting
      nitrogen-donor sites for the purpose of metal ion coordination. The macrocyclic
      structure of 4 was assigned by using spectroscopic methods, and shown to exist in
      a twisted and chiral ground state conformation by semi-empirical theoretical
      calculations. A detailed spectroscopic investigation into the metal ion binding
      properties of 4 and precursor 11 revealed that they functioned as selective
      complexants, affording a fluorescence quenching output response characteristic of
      Pd(II) and Hg(II) ions. Furthermore, 4 also signalled the presence of Fe(II),
      Co(II), Ni(II) and Ag(I) ions by the precipitation of coordination polymers, and
      exhibited reversible proton-triggered fluorescence quenching behaviour.
      Macrocycle 4 thus represents a unique type of molecular sensory platform, which
      may find a wealth of potential applications such as the detection of heavy-metal
      pollutants, as well as for the fabrication of proton-switchable materials and
      coordination polymers with novel electronic and magnetic properties.

PMID- 12794896
TI  - Alkyne migration in alkylidene carbenoid species: a new method of polyyne
      synthesis.
AB  - The synthesis of conjugated polyyne structures via a modification of the Fritsch
      Buttenberg-Wiechell (FBW) rearrangement is reported. Our adaptation provides for
      the 1,2-migration of an alkyne in a carbene/carbenoid intermediate that is
      conveniently effected via lithium-halogen exchange with the appropriate dibromo
      olefinic precursor. This rearrangement is quite rapidly accomplished under mild
      conditions (hexane solution, -78 degrees C), and the seemingly high migratory
      aptitude of the alkynyl moiety provides for efficient rearrangement. This, in
      turn, allows for multiple rearrangements in a single molecule, greatly
      facilitating the construction of highly unsaturated substrates. This procedure is
      exploited for the rapid synthesis of symmetrical and unsymmetrical 1,3,5
      hexatriynes, extended polyynes, and aryl polyyne building blocks. Most
      significantly, many of these structures have been or would be difficult to access
      via more traditional transition metal catalyzed homo- or cross-coupling
      techniques.

PMID- 12794897
TI  - Relative stability of major types of beta-turns as a function of amino acid
      composition: a study based on Ab initio energetic and natural abundance data.
AB  - Folding properties of small globular proteins are determined by their amino acid
      sequence (primary structure). This holds both for local (secondary structure) and
      for global conformational features of linear polypeptides and proteins composed
      from natural amino acid derivatives. It thus provides the rational basis of
      structure prediction algorithms. The shortest secondary structure element, the
      beta-turn, most typically adopts either a type I or a type II form, depending on
      the amino acid composition. Herein we investigate the sequence-dependent folding
      stability of both major types of beta-turns using simple dipeptide models (-Xxx
      Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably
      protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied.
      For each backbone fold most probable side-chain conformers were considered. Fully
      optimized 321G RHF molecular structures were employed in medium level [B3LYP/6
      311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of
      the different backbone conformers. Our results show that the preference for beta
      turn forms as calculated by quantum mechanics and observed in Xray determined
      proteins correlates significantly.

PMID- 12794898
TI  - Synthesis and properties of [CoCp*(2,5-PC4tBu2H2)]: the first
      monophosphacobaltocene.
AB  - The reduction of the phosphacobaltocenium salt [CoCp*(2,5
      PC(4)tBu(2)H(2))](+)[BPh(4)](-) (3; Cp*=pentamethylcyclopentadienyl) by magnesium
      in tetrahydrofuran (THF) furnishes the stable air-sensitive phosphacobaltocene
      [CoCp*(2,5-PC(4)tBu(2)H(2))] (4) in yields of up to 80 %. The crystal structure
      of 4 shows long Co-C(alpha) and short C(alpha)-C(beta)bonds in the phospholyl
      ligand, consistent with a semi-occupied molecular orbital (SOMO) having a"
      symmetry. A combined Amsterdam density functional (ADF)/photoelectron
      spectroscopic study, which confirms this assignment, gives ionisation energies
      (IE) of 5.02 eV from the SOMO and 8.89 eV from the phosphorus "lone pair". A
      comparison of cyclovoltammograms for 3 and the corresponding cyclopentadienyl
      complex [CoCp*(1,3-C(5)tBu(2)H(3))](+) [BPh(4)](-)(5) shows that replacing a CH
      group by an sp(2) phosphorus atom results in an anodic first reduction potential
      shift of 0.29 V.

PMID- 12794899
TI  - A molecular approach to self-assembly of trimethylsilylacetylene derivatives on
      gold.
AB  - We recently discovered that a linear multifunctional trimethylsilylacetylene
      (TMSA) compound forms long-range and highly stable self-assembled monolayers
      (SAMs) on reconstructed Au(111). To better understand the interactions governing
      self-assembly in this new system, we synthesized a series of homologue
      organosilanes and performed scanning tunneling microscopy (STM) measurements at
      the Au(111)/n-tetradecane interface. The four TMSA-terminated linear silanes that
      we synthesized self-assemble in similar ways on gold, with the molecules standing
      upright on the surface. In contrast, compounds with a slightly modified terminal
      group but the same polyunsaturated linear chain above the TMSA head do not self
      assemble. In particular, substituting a methyl group of TMSA with a more bulky
      one prevents self-assembly. Removing the C triple bond C triple bond of TMSA or
      substituting the Si atom by a C atom also hinders self-assembly. Finally,
      substituting one methyl group of TMSA by a hydrogen atom induces self-assembly
      but in a different geometry, with the molecules lying flat on the gold surface in
      a quasi-epitaxy mode. Our molecular approach demonstrates the key role played by
      the TMSA head in self-assembly, its origin being twofold: 1) the TMSA layers are
      commensurate to the Au(111) adlattice along the <112> direction, and 2) the C
      triple bond C triple bond of TMSA activates the Si atom and induces the creation
      of a surface Si-Au chemical bond. The highly stable TMSA-based SAMs appear then
      as promising materials for applications in surface modification.

PMID- 12794900
TI  - Polymer-supported triazenes as smart reagents for the alkylation of carboxylic
      acids.
AB  - Starting from polystyrene, a simple four-step synthesis of polymer-supported
      alkyltriazenes (alkyl=Me, Et, benzyl) is described. With this synthesis, a
      loading capacity of 2.2 mmol g(-1) can be reached. The most prominent application
      of these polymer-supported reagents is the rapid, highly selective and high
      yielding esterification of carboxylic acids, which involves a simple "mix and
      filter off" procedure at room temperature. If stored in a refrigerator, these
      reagents are stable for many months and they can be recycled several times.

PMID- 12794901
TI  - Phospholipase A2 hydrolysis of mixed phospholipid vesicles formed on
      polyelectrolyte hollow capsules.
AB  - Mixtures of the phospholipids L-alpha-dimyristoylphosphatidic acid (DMPA) and L
      alpha-dipalmitoylphosphatidylcholine (DPPC) have been successfully adsorbed onto
      the charged surface of multilayer polyelectrolyte capsules to form a novel
      vesicle. Leaving such vesicles in phospholipase A(2) solution, we observed the
      hydrolysis reaction on the surface of the lipid/polymer vesicles and a
      permeability change before and after the reaction by confocal-laser scanning
      microscopy (CLSM). A capsule with adjustable permeability was constructed. This
      method may provide new features for drug-release vesicles.

PMID- 12794902
TI  - Interplay between solvent and counteranion stabilization of highly unsaturated
      rhodium(III) complexes: facile unsaturation-induced dearomatization.
AB  - Abstraction of the chloride ligand from the PCN-based chloromethylrhodium complex
      2 by AgX (X=BF(4)(-), CF(3)SO(3)(-)) or a direct C-C cleavage reaction of the PCN
      ligand 1 with [(coe)(2)Rh(solv)(n)](+)X(-) (coe=cyclooctene) lead to the
      formation of the coordinatively unsaturated rhodium(III) complexes 3. Compound 3
      a (X=BF(4)(-)) exhibits a unique medium effect; the metal center is stabilized by
      reversible coordination of the bulky counteranion or solvent as a function of
      temperature. Reaction of [(PCN)Rh(CH(3))(Cl)] with AgBAr(f) in diethyl ether
      leads to an apparent rhodium(III) 14-electron complex 4, which is stabilized by
      reversible, weak coordination of a solvent molecule. This complex coordinates
      donors as weak as diethyl ether and dichloromethane. Upon substitution of the
      BF(4)(-) ion in [(PCN)Rh(CH(3))]BF(4) by the noncoordinating BAr(f)(-) ion in a
      noncoordinating medium, the resulting highly unsaturated intermediate undergoes a
      1,2-metal-to-carbon methyl shift, followed by beta-hydrogen elimination, leading
      to the Rh-stabilized methylene arenium complex 5. This process represents a
      unique mild, dearomatization of the aromatic system induced by unsaturation.

PMID- 12794904
TI  - Facile optical resolution of tert-butanethiosulfinate by molecular complexation
      with (R)-BINOL and study of chiral discrimination of the diastereomeric
      complexes.
AB  - An important synthon, tert-butanethiosulfinate (2), has been effectively resolved
      by forming molecular complexes with (R)-2,2'-dihydroxy-1,1'-binaphthyl (BINOL, 3)
      in high enantioselectivity (>99 % ee). The present procedure represents the first
      example of the resolution of thiosulfinate. The mechanism of chiral
      discrimination is discussed in terms of molecular recognition based on IR and
      Xray analyses of the diastereomeric complexes during the resolution. In the less
      soluble complex, (R)-3 and (R)-2 self-assembled as a linear supramolecule;
      however, in the more-soluble complex, (R)-3 and (S)-2 formed a simple bimolecular
      complex by one stronger hydrogen bond. Hydrogen bonding is the major driving
      force for effective resolution.

PMID- 12794903
TI  - Synthesis of complex oligosaccharides by using a mutated (1,3)-beta-D-glucan
      endohydrolase from barley.
AB  - Complex oligosaccharides with newly formed (1,3)-beta-glycosidic linkages were
      obtained in good to excellent yields when substituted or unsubstituted alpha
      laminaribiosyl fluorides, acting as donors, were condensed onto mono- and
      disaccharide beta-D-hexopyranoside acceptors by using a (1,3)-beta-D
      glycosynthase. These linear and branched (1,3)-beta-linked oligosaccharides could
      prove to be important in a range of medical, pharmaceutical, and agricultural
      applications. Furthermore, the observation that the (1,3)-beta-D-glucan
      glycosynthase accommodates (1,3)-, (1,4),- and (1,6)-beta-oligosaccharides in its
      acceptor subsites suggests novel, yet unexpected physiological roles for the wild
      type (1,3)-beta-D-glucan endohydrolase from higher plants.

PMID- 12794905
TI  - The 1deltag dioxygen ene reaction with propene: a density functional and
      multireference perturbation theory mechanistic study.
AB  - This study aims to determine whether a balance between concerted and non
      concerted pathways exists, and in particular to ascertain the possible role of
      diradical/zwitterion or peroxirane intermediates. Three non-concerted pathways,
      via 1) diradical or 2) peroxirane intermediates, and 3) by means of hydrogen
      abstraction/radical recoupling, plus one concerted pathway (4), are explored. The
      intermediates and transition structures (TS) are optimized at the DFT(MPW1K),
      DFT(B3LYP) and CASSCF levels of theory. The latter optimizations are followed by
      multireference perturbative CASPT2 energy calculations. (1) The polar diradical
      forms from the separate reactants by surmounting a barrier (deltaE(++)(MPW1K)=12,
      deltaE++(B3LYP)=14, and deltaE(++)(CASPT2)=16 kcal mol(-1) and can back
      dissociate through the same TS, with barriers of 11 (MPW1K) and 8 kcal mol(-1)
      (B3LYP and CASPT2). The diradical to hydroperoxide transformation is easy at all
      levels (deltaE(++)(MPW1K)<4, deltaE(++)(B3LYP)=1 and deltaE(++)(CASPT2)=1 kcal
      mol(-1)). (2) Peroxirane is attainable only by passing through the diradical
      intermediate, and not directly, due to the nature of the critical points
      involved. It is located higher in energy than the diradical by 12 kcal mol(-1),
      at all theory levels. The energy barrier for the diradical to cis-peroxirane
      transformation (deltaE(++)=14-16 kcal mol(-1)) is much higher than that for the
      diradical transformation to the hydroperoxide. In addition, peroxirane can very
      easily back-transform to the diradical (deltaE(++)<3 kcal mol(-1)). Not only the
      energetics, but also the qualitative features of the energy hypersurface, prevent
      a pathway connecting the peroxirane to the hydroperoxide at all levels of theory.
      (3) The last two-step pathway (hydrogen-abstraction by (1)O(2), followed by HOO
      allyl radical coupling) is not competitive with the diradical mechanism. (4) A
      concerted pathway is carefully investigated, and deemed an artifact of restricted
      DFT calculations. Finally, the possible ene/[pi2+pi2] competition is discussed.

PMID- 12794906
TI  - Reaction of enol ethers with alkynes catalyzed by transition metals: 5-exo-dig
      versus 6-endo-dig cyclizations via cyclopropyl platinum or gold carbene
      complexes.
AB  - The intramolecular reaction of enol ethers with alkynes in methanol is catalyzed
      by electrophilic Pt(II), Pd(II), and Au(III) chlorides and by a Cu(I) complex to
      give five- or six-membered rings bearing dimethyl acetals. The reaction takes
      place by an anti addition of the enol ether and the metal to the alkyne. The
      possible involvement of vinylidene complexes in this reaction is excluded. In
      addition to the usual 5-exo-dig (or 6-exo-dig) pathways, a 6-endo-dig pathway has
      also been found to take place with certain enynes. One case of 5-endo-dig
      cyclization has also been found. A general scheme for the alkoxycyclization of
      enynes catalyzed by transition metals based on DFT calculation of PtCl(2) and
      AuCl(3) complexes that includes exo and endo cyclizations is presented.

PMID- 12794907
TI  - Electronic coupling in a highly preorganized bimetallic complex comprising
      pyrazolate-bridged CpMn(CO)2 moieties.
AB  - By means of a multistep synthetic procedure a dimanganese complex has been
      prepared, in which a N,N'-bridging pyrazolate ligand spans two CpMn(CO)(2)
      subunits in a highly preorganized chelate arrangement. The Xray crystallographic
      analyses of the Mn(I)Mn(I) complex K(+)1(-) and of its non-chelate precursor
      complex elucidate details of the molecular structure, in particular an unusual
      pyrazolate binding mode in the solid state and intertwining of the CO ligands in
      the crowded bimetallic array 1(-). The Mn(I)Mn(I) compound (1(-)), the mixed
      valent Mn(I)Mn(II) (1), and the oxidized Mn(II)Mn(II) form (1(+)) have been
      characterized by various analytical and spectrosopic methods, such as
      electrochemistry, variable-temperature EPR spectroscopy, IR
      spectroelectrochemistry, and UV/Vis/NIR spectroelectrochemistry as well as by DFT
      and TD-DFT calculations. Strong electronic coupling in the mixed-valent complex
      is observed, but time- (and temperature-) dependent valence detrapping occurs,
      thus placing 1 in class II according to the Robin and Day assignment, close to
      the class II/III transition. From variable-temperature EPR spectroscopy a rough
      estimate of the activation energy and rate for thermal electron transfer can be
      deduced, with E(th) ( not equal )=13.6 kJ mol(-1) and k(th)=2.6 x 10(10) s(-1) at
      298 K. Unexpectedly, no intervalence CT transition for 1 is detected in solution,
      but one appears in the optical spectrum of solid 1. The conclusions drawn from
      experiments are fully supported by DFT calculations that were carried out for all
      three forms of the dimanganese complex. A broken symmetry treatment for mixed
      valent 1 reveals almost perfect localization of both spin and charge on one Mn
      center. According to TD-DFT the first excited states of 1 give rise to the IT
      processes in the NIR-energy region, as observed in the solid-state spectrum. The
      HOMOs are located at the Mn ions and are favorably arranged for pi interactions
      with the bridging pyrazolate.

PMID- 12794908
TI  - Photoinduced electron transfer between the interlocked components of porphyrin
      catenanes: effect of the presence of nonequivalent reduction sites on the charge
      recombination rate.
AB  - [2]Catenanes made up of several polyether-strapped porphyrin macrocycles
      interlinked with the cyclic electron acceptor cyclobis(paraquat-p-phenylene) were
      spectroscopically, photophysically, and electrochemically characterized. The
      catenanes exhibit very rich redox behavior due to the presence of several
      different and interacting electro-active subunits. The redox patterns represent
      useful "fingerprints" that provide detailed information on the electronic
      interactions and the chemical environments that the electroactive subunits
      experience in the supramolecular arrays. A photoinduced electron transfer from
      the porphyrin excited state (charge separation CS) occurs with tau=20 ps in the
      catenanes with a larger strap and faster than 20 ps (instrumental resolution) in
      the catenanes with a shorter strap. The resulting charge-separated state
      recombines to the ground state (charge recombination CR) with lifetimes similar
      in all cases, 41+/-4 ps. Comparison of the electron transfer rates CS and CR in
      the host-guest complexes of the same porphyrins with the noncyclic electron
      acceptor paraquat, indicate slower reactions in the [2]catenanes. This behavior
      is assigned to the different separation between reacting partners determined by
      the type of bond (weak interaction or mechanical) and to a two-step consecutive
      electron transfer to different sites of the macrocyclic electron acceptor in the
      catenanes which retards charge recombination.

PMID- 12794910
TI  - Documentation and three-dimensional modelling of human soleus muscle
      architecture.
AB  - The purpose of this study was to visualize and document the architecture of the
      human soleus muscle throughout its entire volume. The architecture was visualized
      by creating a three-dimensional (3D) manipulatable computer model of an entire
      cadaveric soleus, in situ, using B-spline solid to display muscle fiber bundles
      that had been serially dissected, pinned, and digitized. A database of fiber
      bundle length and angle of pennation throughout the marginal, posterior, and
      anterior soleus was compiled. The computer model allowed documentation of the
      architectural parameters in 3D space, with the angle of pennation being measured
      relative to the tangent plane of the point of attachment of a fiber bundle.
      Before this study, the only architectural parameters that have been recorded have
      been 2D. Three-dimensional reconstruction is an exciting innovation because it
      makes feasible the creation of an architectural database and allows visualization
      of each fiber bundle in situ from any perspective. It was concluded that the
      architecture is non-uniform throughout the volume of soleus. Detailed
      architectural studies may lead to the development of muscle models that can more
      accurately predict interaction between muscle parts, force generation, and the
      effect of pathologic states on muscle function.

PMID- 12794911
TI  - Anatomical variations and clinical implications of the artery to the lingual
      nerve.
AB  - The pterygomandibular space is a critical anatomic area for the delivery of local
      anesthesia in the practice of dentistry. The neurovascular contents of this area
      are subject to trauma and its resultant local and systemic complications. This
      study of 202 cadaveric specimens reaffirms the literature as to the percent
      distributions of the superficial and deep routes of the maxillary artery and
      details for the first time the anatomic variations of the artery to the lingual
      nerve. This artery courses through the pterygomandibular space placing it at risk
      for injection trauma along with the other neurovascular contents. It has been
      uncommonly identified and referred to in the literature, yet it may be the first
      artery encountered when entering the space with a needle or during surgical
      intervention in the area.

PMID- 12794912
TI  - Plastination and computerized 3D reconstruction of the temporal bone.
AB  - The purpose of this study was to generate a computerized 3D reconstruction of the
      temporal bone and intratemporal structures. A plastination technique was used to
      obtain equidistant serial thin sections of 1.2 mm thickness and, on an SGI
      workstation, a Contour-Marching Cubes algorithm was selected to reconstruct the
      temporal bone and intratemporal structures in three dimensions. All reconstructed
      structures can be represented individually or jointly and rotated in any plane.
      Any diameter and angle of a structure can be conveniently measured. The
      capability of reconstructing individual and combined images of intratemporal
      structures, viewing them from all surgical angles, and accurately measuring their
      spatial relationships gives skull base and otologic surgeons important guidance.
      The reconstructed model can also be used for resident education, rehearsal of an
      unfamiliar surgery, and for developing a new surgical approach.

PMID- 12794914
TI  - Lateral femoral cutaneous neuralgia: an anatomical insight.
AB  - A detailed anatomic study was carried out on the lateral femoral cutaneous nerve
      to better understand the etiology and treatment of lateral femoral cutaneous
      neuralgia. As it passed from the pelvis into the thigh, the lateral femoral
      cutaneous nerve ran through an "aponeuroticofascial tunnel," beginning at the
      iliopubic tract and ending at the inguinal ligament; as it passed through the
      tunnel, an enlargement in its side-to-side diameter was observed, suggesting that
      the fascial structures proximal to the inguinal ligament may be implicated in the
      genesis of lateral femoral cutaneous neuralgia. The finding of pseudoneuromas at
      this location, distant from the inguinal ligament, supports this hypothesis. The
      anterior superior iliac spine is located approximately 0.7 cm from the lateral
      femoral cutaneous nerve and serves as the bony landmark for nerve localization.
      Within the first 3 cm of leaving the pelvis, the lateral femoral cutaneous nerve
      was observed deep to the fascia lata; therefore, surgical dissection within the
      subcutaneous fascia may be conducted with relative impunity near the anterior
      superior iliac spine just inferior to the inguinal ligament. In 36% of cases
      there was no posterior branch of the nerve, which is correlated to lateral
      femoral cutaneous neuralgia symptoms often being limited to the anterior branch
      region. An accessory nerve was found in 30% of cases.

PMID- 12794913
TI  - Comparison of qualitative and quantitative analyses of age-related changes in
      clivus bone marrow on MR imaging.
AB  - Magnetic resonance (MR) imaging is capable of detecting a wide spectrum of
      diseases involving clivus bone marrow. To evaluate any pathology in this region,
      the normal MR signal intensity patterns according to age should be known.
      Assessment of clivus bone marrow is usually and more efficiently made visually
      (qualitatively) on routine MR imaging. To compare the qualitative and
      quantitative analyses of age-related changes in clivus bone marrow on MR imaging,
      midsagittal T1-weighted MR images of the clivus bone marrow were prospectively
      evaluated in 201 subjects. MR signal intensity patterns of clivus bone marrow
      were qualitatively graded from I to III according to the proportions of low and
      high signal intensity areas within the clivus (Grade I: predominantly
      hypointense, Grade III: predominantly hyperintense). Signal intensity
      measurements were also made from the clivus, pons, and the cerebrospinal fluid
      within the fourth ventricle. Grade I pattern was observed in 92% of the subjects
      in the first decade, whereas Grade III pattern was not seen in this decade; Grade
      I pattern was absent in all but one of the subjects over the age of 50. Mean
      values of clivus/pons and clivus/CSF signal intensity measurements gradually
      increased with age in both males and females. Comparison of these ratios in each
      gender showed statistically significant higher values for males (P < 0.05).
      Comparison of the qualitative and quantitative results showed that calculated
      mean values of intensity ratios for each grade were different from each other;
      however, there was an overlap of the ranges of signal intensity ratios for Grades
      II and III. Visual evaluation of the clivus bone marrow MR signal is validated
      with the quantitative assessment results. Statistically significant higher
      intensity ratios in males may reflect a difference between gender in the bone
      mineral content under the influence of sex hormones.

PMID- 12794916
TI  - Calcaneal angle in Ugandans.
AB  - We investigated the calcaneal angle from 206 unilateral radiographs of the
      lateral aspect of the foot in Ugandans, comprising 114 males and 92 females, aged
      20-40 years. The mean angle in males was 35.1 degrees with a standard deviation
      (SD) of 7.5 degrees and, in females, 37.6 degrees with SD 5.6 degrees. The range
      of the angle for both sexes together was 20-50 degrees with females having a
      significantly higher mean value than males (P < 0.01). There was also a
      significant difference in the angle between Ugandan and Nigerian men (P < 0.01)
      and between Ugandan and Nigerian women (P < 0.001). Our reported range was the
      widest so far documented in Africans. Our study reinforces the need to establish
      the normal range of the angle in a given population and also highlights the
      clinical importance of the angle to orthopedic surgeons managing calcaneal
      fractures in this part of the world.

PMID- 12794915
TI  - Vascular changes in duodenal mucosa in shigellosis and cholera.
AB  - Vascular endothelial cells are highly specialized cells with numerous sensory and
      modulator functions. Our previous studies show extensive microvascular changes in
      rectal mucosal vasculature of patients with acute infective diarrhea (Mathan and
      Mathan 1985a, Gut 26:710-717). We looked for changes in the duodenal mucosal
      vasculature in two naturally occurring diarrheal infections: shigellosis and
      cholera. Duodenal mucosal biopsies from 14 patients with shigellosis, 12 patients
      with cholera, and 10 healthy volunteers were examined under the electron
      microscope. There were extensive microvascular changes in the duodenum in
      shigellosis and cholera. Congestion and dilatation of capillaries and venules,
      stagnation of blood, thinning of the endothelial lining, and platelet clumping
      were commonly seen in both conditions. Endothelial damage was also common to both
      conditions but was mild to moderate in cholera and severe in shigellosis with
      frank hemorrhage, frequent formation of stress fibers, widening of intercellular
      spaces, cytoplasmic blebbing, cell fragmentation, and intravascular thrombosis.
      Erythrocyte aggregates, platelet aggregates, and leucocyte plugging lead to
      capillary obstruction. The arterioles were severely constricted. These changes in
      the endothelial lining of the microvasculature could contribute to the
      pathogenesis of the disease resulting in peripheral vascular insufficiency,
      inadequate oxygen delivery to intestine, and organ dysfunction. The factors
      influencing these changes, their implications, and possible therapeutic
      interventions are discussed.

PMID- 12794917
TI  - Left atrial isomerism: clinicopathologic findings in a 14-year-old boy.
AB  - Visceral heterotaxy syndromes have been associated with complex congenital heart
      disease and several attempts have been made to classify these lesions. One area
      of controversy that remains is the existence of atrial isomerism. In this case
      report we provide definite anatomic evidence of the existence of left atrial
      isomerism, wherein both the atria have smooth walls, finger-like appendages, and
      absence of the pectinate muscles and sinus node.

PMID- 12794918
TI  - Median nerve penetration by a muscular branch of the brachial artery.
AB  - Arterial variations in the distal half of the arm are common (Anagnostopoulou and
      Venieratos 1999, J. Anat. 195:471-476). We observed a rare variant of a muscular
      branch of the brachial artery that penetrated the median nerve in the lower part
      of the arm. After its origin from the posteromedial surface of the brachial
      artery, the muscular branch passed through a nervous loop in the median nerve to
      enter and supply the brachialis muscle. At the site of arterial penetration, the
      nerve displayed perineurial thickening and increased fasciculation and
      interfascicular connective tissue. Three small branches of the artery supplied
      the nerve fascicles. We did not observe nerve compression or muscular changes,
      but the possibility of altered clinical symptoms produced by irritation from
      arterial pulsation cannot be ruled out. This variation may be clinically
      important because symptoms of median nerve compression arising from similar
      variations are often confused with more common causes, such as radiculopathy and
      carpal tunnel syndrome.

PMID- 12794919
TI  - Anomalous flexor digiti minimi brevis in Guyon's canal.
AB  - In an adult male cadaver, the flexor digiti minimi brevis, a muscle of the
      hypothenar eminence, was found to arise from the superficial transverse septum
      (between the superficially placed flexor carpi ulnaris, palmaris longus, and
      flexor carpi radialis muscles, and the deeply placed flexor digitorum
      superficialis muscle) in the distal fourth of the flexor aspect of the left
      forearm. The muscle exhibited two strata of muscle fibers at its origin. The
      superficial stratum was a thin layer of transversely running fibers confined to
      the forearm, which has not been previously reported. The deep stratum, a thick
      layer of longitudinally running fibers, formed the bulk of the muscle. It
      traversed Guyon's canal superficial to the ulnar nerve and vessels to reach the
      hypothenar eminence. Its course through Guyon's canal could be a cause for ulnar
      tunnel syndrome. The ulnar nerve trunk innervated not only the anomalous flexor
      digiti minimi brevis muscle, but also abductor digiti minimi and palmaris brevis.
      This may be due to the common phylogeny of these three muscles from the same
      muscle mass.

PMID- 12794920
TI  - Dual sensory innervation of the dorsum of the thumb.
AB  - The value of the thumb has been described as being almost equal to the rest of
      the fingers combined (Decker and du Plessis, eds. 1986, Lee McGregor's synopsis
      of surgical anatomy. 12th ed. p 496). Normal hand function is dependent upon the
      integrity of both the sensory and motor innervation of the thumb. A thorough
      knowledge of normal and anomalous sensory innervation of the digits has clinical
      application because of the increased use of local anesthesia and developments in
      plastic surgery involving the skin of the digits. Herein is reported an unusual
      variation in the sensory innervation of the thumb in an adult cadaver. The normal
      innervation of the dorsum of the thumb is reviewed, and the clinical importance
      of this variation is discussed.

PMID- 12794921
TI  - Bilateral asymmetric deficiency of the pectoralis major muscle.
AB  - We observed a rare, bilateral congenital deficiency of the pectoralis major
      muscle in a 72-year-old female cadaver in our gross anatomy dissection
      laboratory. The outward appearance of the anterior thoracic wall, which included
      well-developed breasts, revealed no obvious abnormalities. Upon dissection, the
      following features were observed: 1) on the left side, the sternal portion of the
      sternocostal head of the pectoralis major muscle was absent, the costal portion
      of the sternocostal head and the clavicular head were both well developed, a
      normal pectoralis minor was present, and the deltoid and subclavius muscles were
      not hypertrophied as is often the case when the pectoralis major muscle is
      deficient; 2) on the right side, the entire pectoralis major muscle was absent
      and the pectoralis minor, deltoid, and coracobrachialis muscles were infiltrated
      with connective tissue and fat; and 3) on both sides, the lateral pectoral nerves
      were absent and the medial pectoral nerves were present. The absence of the
      lateral pectoral nerves suggests that the deficiencies in the pectoralis major
      muscles are congenital malformations resulting from a developmental failure of
      the embryonic muscles rather than a sequel to polio or Poland's syndrome.

PMID- 12794922
TI  - Left musculus sternalis.
AB  - During routine dissection in the Morphological Sciences Department II of the
      Universidad Complutense de Madrid, the presence of a sternalis muscle was
      observed in the left hemithorax of a 70-year-old male cadaver. We report on its
      position, relationships, and innervation, as well as its clinical relevance,
      indicating some guidelines for its physical examination. We also present a brief
      overview of the existing literature regarding the nomenclature, historical
      reports, and incidence of this muscle.

PMID- 12794923
TI  - Duplicated inferior vena cava and crossed renal ectopia with abdominal aortic
      aneurysm: preoperative anatomic studies facilitate surgery.
AB  - Abdominal aortic aneurysm in association with duplication of the inferior vena
      cava and crossed renal ectopia is described for the first time. Preoperative
      imaging with computer-aided tomography provided good visualization of the local
      anatomy, allowing the surgical approach to be adapted for the best access to the
      surgical site. A retroperitoneal approach was successfully used for repair of the
      abdominal aortic aneurysm.

PMID- 12794924
TI  - Pivotal role of the sub-supracardinal anastomosis in the development and course
      of the left renal vein.
AB  - A retroaortic left renal vein is encountered frequently in the dissecting room
      and in radiological investigations. A number of recent reports of this variation
      led us to review the development of the renal veins and the inferior vena cava to
      understand its etiology. For further insight, we also examined our collection of
      serial sections of cat embryos. In human embryos of about 15 mm the "renal
      collar," a venous ring around the aorta, is formed by anastomoses between
      subcardinal and supracardinal veins. The ventral part of the "renal collar" is
      formed from the intersubcardinal anastomosis, the dorsal part from the
      intersupracardinal anastomosis and the lateral parts from the sub-supracardinal
      anastomoses. The primitive renal veins drain venous blood from the metanephros
      into the sub-supracardinal anastomoses. A retroaortic left renal vein would form
      if the dorsal part of the sub-supracardinal anastomosis and the
      intersupracardinal anastomosis persist whereas the ventral part of the sub
      supracardinal anastomosis and the intersubcardinal anastomosis regress.

PMID- 12794925
TI  - Prolonged facial hypesthesia resulting from greater occipital nerve block.

PMID- 12794927
TI  - Radial nerve innervation to the inferolateral segment of the brachialis muscle:
      from anatomy to clinical reality.

PMID- 12794928
TI  - Functional characterization of a H+/nucleoside co-transporter (CaCNT) from
      Candida albicans, a fungal member of the concentrative nucleoside transporter
      (CNT) family of membrane proteins.
AB  - Human and other mammalian concentrative (Na(+)-linked) nucleoside transport
      proteins belong to a membrane protein family (CNT, TC 2.A.41) that also includes
      Escherichia coli H(+)-dependent nucleoside transport protein NupC. Here, we
      report the cDNA cloning and functional characterization of a CNT family member
      from the pathogenic yeast Candida albicans. This 608 amino acid residue
      H(+)/nucleoside symporter, designated CaCNT, contains 13 predicted transmembrane
      domains (TMs), but lacks the exofacial, glycosylated carboxyl-terminus of its
      mammalian counterparts. When produced in Xenopus oocytes, CaCNT exhibited
      transport activity for adenosine, uridine, inosine and guanosine but not
      cytidine, thymidine or the nucleobase hypoxanthine. Apparent K(m) values were in
      the range 16-64 micro M, with V(max) : K(m) ratios of 0.58-1.31. CaCNT also
      accepted purine and uridine analogue nucleoside drugs as permeants, including
      cordycepin (3'-deoxyadenosine), a nucleoside analogue with anti-fungal activity.
      Electrophysiological measurements under voltage clamp conditions gave a H(+) to
      [(14)C]uridine coupling ratio of 1 : 1. CaCNT, obtained from logarithmically
      growing cells, is the first described cation-coupled nucleoside transporter in
      yeast, and the first member of the CNT family of proteins to be characterized
      from a unicellular eukaryotic organism.

PMID- 12794929
TI  - Isolation and characterization of the TRP1 gene from the yeast Yarrowia
      lipolytica and multiple gene disruption using a TRP blaster.
AB  - The TRP1 gene encoding N-(5'-phosphoribosyl)-anthranilate isomerase was isolated
      from the yeast Yarrowia lipolytica, in which only a few genetic marker genes are
      available. The Y. lipolytica TRP1 gene (YlTRP1) cloned by complementation of Y.
      lipolytica trp1 mutation was found to be a functional homologue of Saccharomyces
      cerevisiae TRP1. Since YlTRP1 could be used for counterselection in medium
      containing 5-fluoroanthranilic acid (5-FAA), we constructed TRP blasters that
      contained YlTRP1 flanked by a direct repeat of a sequence and allowed the
      recycling of the YlTRP1 marker. Using the TRP blasters the sequential disruption
      of target genes could be carried out within the same strain of Y. lipolytica. The
      nucleotide sequence of the YlTRP1 gene has been deposited at GenBank under
      Accession No. AF420590.

PMID- 12794930
TI  - Development of a reporter system for the yeast Schwanniomyces occidentalis:
      influence of DNA composition and codon usage.
AB  - In this paper we report on searching for suitable reporters to monitor gene
      expression and protein secretion in the amylolytic yeast Schwanniomyces
      occidentalis. Several potential reporter and marker genes, formerly shown to be
      functional in other yeasts, were cloned downstream from the homologous invertase
      gene (INV) promoter and their activity was followed in conditions of repression
      and derepression of the INV promoter. However, neither beta-glucuronidase nor
      beta-lactamase nor phleomycin resistance-conferring gene, all originating from E.
      coli, were expressed in S. occidentalis cells to such a level to allow for
      monitoring of their activity. All the reporter genes tested have a higher
      percentage of GC (47-62%) in their DNA compared to the DNA composition of S.
      occidentalis genes that are more AT-rich (36% GC). The codon usage of all the
      reporter genes also varies from that of 16 so far sequenced S. occidentalis
      genes. This suggests that an appropriate composition of DNA and a codon usage
      similar to S. occidentalis genes might be very important parameters for an
      efficient expression of a heterologous gene in Schwanniomyces occidentalis.
      Indeed, two genes originating from Staphylococcus aureus, with an AT-content in
      their DNA similar to that of S. occidentalis, were functionally expressed in S.
      occidentalis cells. Both a phleomycin resistance-conferring gene and a
      chloramphenicol acetyltransferase-encoding gene thus represent suitable reporters
      of gene expression and protein secretion in S. occidentalis. Additionally, we
      show in this work that the transcription-regulating region and the signal peptide
      sequence of the S. occidentalis invertase gene were efficient to direct gene
      expression and subsequent protein secretion in Saccharomyces cerevisiae.

PMID- 12794931
TI  - Relationship between G+C content, ORF-length and mRNA concentration in
      Saccharomyces cerevisiae.
AB  - RNA biogenesis is a tightly-regulated process. The levels and timing of
      expression of a gene depends on its particular function. However, gene expression
      levels may also depend on structural features. Here we describe the analysis of
      gene expression of 4977 ORFs using DNA microarrays covering the whole genome of
      three different S. cerevisiae strains, wild-type and tho2 and thp1 mutants with a
      general effect on mRNA biogenesis. We show that transcripts from G+C-rich ORFs
      accumulate at higher concentrations than those from G+C-poor ones, in different
      ORF-length categories in all strains tested. In addition, we found a negative
      correlation between ORF length and G+C content. Our results indicate that length
      and G+C content of a gene have a clear effect on its levels of expression. We
      discuss the biological relevance of these results, as well as different ways that
      these structural features could modulate mRNA biogenesis.

PMID- 12794932
TI  - Candida albicans TDH3 gene promotes secretion of internal invertase when
      expressed in Saccharomyces cerevisiae as a glyceraldehyde-3-phosphate
      dehydrogenase-invertase fusion protein.
AB  - We have checked the ability of the Candida albicans GAPDH polypeptide, which
      lacks a conventional N-terminal signal peptide, to reach the cell wall in
      Saccharomyces cerevisiae by using an intracellular form of the yeast invertase as
      a reporter protein. A hybrid TDH3-SUC2 gene containing the C. albicans TDH3
      promoter sequences and a coding region encoding a fusion protein formed by the C.
      albicans GAPDH polypeptide, fused at its C-terminus with the yeast internal
      invertase, was constructed in a centromer derivative plasmid and transformed into
      a Suc(-) S. cerevisiae strain. Transformants displayed invertase activity
      measured in intact whole cells, and were able to grow on sucrose as the sole
      fermentable carbon source. Northern blot analysis with both TDH3 and SUC2 probes
      detected a single mRNA species of the expected size (about 2.7 kb), and Western
      immunoblot analysis of cell-free extracts, using a monoclonal antibody (mAb49)
      against a C. albicans GAPDH epitope, showed the presence of a 90 kDa polypeptide
      corresponding to the GAPDH-invertase fusion protein. This indicates that the TDH3
      gene is able to direct part of the encoded gene product to the cell wall, and
      that any putative motifs for this targeting should be within the GAPDH amino acid
      sequence. Further analysis, using the same approach, of a panel of seven N- and C
      terminal GAPDH truncates revealed that the region required for the cell wall
      targeting is located within the N-terminal half of the protein.

PMID- 12794933
TI  - Genes involved in beta-oxidation, energy metabolism and glyoxylate cycle are
      induced by Candida albicans during macrophage infection.
AB  - The ability of intracellular pathogens to cause infection is related to their
      capacity to survive and grow inside macrophages or in other cell types. Candida
      albicans latent virulence is likely to be related to a similar mechanism of
      avoiding killing by specialized cells and to the resulting ability to grow in
      such hostile environments. Using a differential display reverse transcription
      polymerase chain reaction technique, we have identified seven genes induced in C.
      albicans during macrophage phagocytosis. Sequence analyses and database searches
      revealed that these cDNAs coded for proteins homologous to yeast metabolic
      proteins. Interestingly, four of them are putative peroxisomal proteins, and two
      are involved in environmental signal sensing and transduction. Among the seven
      genes induced by C. albicans, six represent new information that were not
      described in other infection models.

PMID- 12794934
TI  - Verification of a new gene on Saccharomyces cerevisiae chromosome III.
AB  - We present verification of the existence of a previously unannotated, intron
      containing gene of 134 amino acids (predicted molecular weight approximately 15.5
      kDa) located on chromosome III of Saccharomyces cerevisiae. Strains carrying a
      deletion of this gene, which we have called YCL012C, reveal no apparent
      phenotype. Orthologues of YCL012C are present in related species S. bayanus, S.
      paradoxus and Ashbya gossypii. Comparison with other fungal sequences reveals
      that orthologues of this gene are likely present in Schizosaccharomyces pombe,
      Neurospora crassa and Cryptococcus neoformans as well, indicating that YCL012C is
      a widely conserved fungal gene.

PMID- 12794935
TI  - Construction of a set of Saccharomyces cerevisiae vectors designed for
      recombinational cloning.
AB  - The Gateway technology is becoming an increasingly popular method for cloning
      ORFs by recombination. It allows the transfer of any ORF flanked by specific
      recombination sites into any vectors harbouring the corresponding sites. Here we
      describe the construction of a set of 20 Saccharomyces cerevisiae Gateway
      compatible vectors. These plasmids bear an URA3 or TRP1 selection marker. They
      are designed for expression without tag sequence or for C- or N-terminal protein
      tagging with 3HA (haemagglutinin), 13MYC, 4TAP (tandem affinity purification) or
      GST (glutathione S-transferase) epitopes. The centromeric vectors allow
      expression of DNA sequence in yeast under tetracycline-regulatable promoters,
      while expression from the high copy vectors is driven by PGK promoter. To test
      their applicability, the genes encoding the RNA polymerase I subunit Rpa12p or
      the TFIIS transcription factor were cloned in these vectors. Their expression was
      demonstrated using Western blotting or complementation assays.

PMID- 12794936
TI  - Response to acetaldehyde stress in the yeast Saccharomyces cerevisiae involves a
      strain-dependent regulation of several ALD genes and is mediated by the general
      stress response pathway.
AB  - One of the stress conditions that yeast may encounter is the presence of
      acetaldehyde. In a previous study we identified that, in response to this stress,
      several HSP genes are induced that are also involved in the response to other
      forms of stress. Aldehyde dehydrogenases (ALDH) play an important role in yeast
      acetaldehyde metabolism (e.g. when cells are growing in ethanol). In this work we
      analyse the expression of the genes encoding these enzymes (ALD) and also the
      corresponding enzymatic activities under several growth conditions. We
      investigate three kinds of yeast strains: laboratory strains, strains involved in
      the alcoholic fermentation stage of wine production and flor yeasts (responsible
      for the biological ageing of sherry wines). The latter are very important to
      consider because they grow in media containing high ethanol concentrations, and
      produce important amounts of acetaldehyde. Under several growth conditions,
      further addition of acetaldehyde or ethanol in flor yeasts induced the expression
      of some ALD genes and led to an increase in ALDH activity. This result is
      consistent with their need to obtain energy from ethanol during biological ageing
      processes. Our data also suggest that post-transcriptional and/or post
      translational mechanisms are involved in regulating the activity of these
      enzymes. Finally, analyses indicate that the Msn2/4p and Hsf1p transcription
      factors are necessary for HSP26, ALD2/3 and ALD4 gene expression under
      acetaldehyde stress, while PKA represses the expression of these genes.

PMID- 12794937
TI  - Therapy and prophylaxis of inhaled biological toxins.
AB  - This review highlights the current lack of therapeutic and prophylactic
      treatments for use against inhaled biological toxins, especially those considered
      as potential biological warfare (BW) or terrorist threats. Although vaccine
      development remains a priority, the use of rapidly deployable adjunctive
      therapeutic or prophylactic drugs could be life-saving in severe cases of
      intoxication or where vaccination has not been possible or immunity not
      established. The current lack of such drugs is due to many factors. Thus, methods
      involving molecular modelling are limited by the extent to which the cellular
      receptor sites and mode of action and structure of a toxin need to be known.
      There is also our general lack of knowledge of what effect individual toxins will
      have when inhaled into the lungs - whether and to what extent the action will be
      cell specific and cytotoxic or rather an acute inflammatory response requiring
      the use of immunomodulators. Possible sources of specific high-affinity toxin
      antagonists being investigated include monoclonal antibodies, selected
      oligonucleotides (aptamers) and derivatized dendritic polymers (dendrimers). The
      initial selection of suitable agents of these kinds can be made using
      cytotoxicity assays involving cultured normal human lung cells and a range of
      suitable indicators. The possibility that a mixture of selected antibody, aptamer
      or dendrimer-based materials for one or more toxins could be delivered
      simultaneously as injections or as inhaled aerosol sprays should be investigated.

PMID- 12794938
TI  - Effect of textile waste water on the spermatogenesis of male albino rats.
AB  - Textile waste water released from dyeing and printing industries situated in
      Sanganer, Jaipur (India), brought about inhibition of spermatogenesis in male
      rats. Water analysis showed the presence of heavy metals at more than permissible
      limits. Oral administration of waste water to the rats at the dose level of 26.6
      ml kg(-1) body wt. significantly reduced the weights of testes, epididymides and
      seminal vesicle. Treated animals showed a notable depression of various stages of
      spermatogenesis. The production of spermatids was inhibited by 70.8% in waste
      water-treated rats. The populations of spermatogonia, preleptotene spermatocytes
      and secondary spermatocytes were decreased by 67.2, 71.1 and 73.2%, respectively.
      The total number of Sertoli cells was affected after waste water treatment.
      Reduced sperm count and motility resulted in treated groups. A significant fall
      in the content of various biochemical parameters of reproductive tissues was
      observed after water treatment.

PMID- 12794939
TI  - Putative role of proteolysis and inflammatory response in the toxicity of nerve
      and blister chemical warfare agents: implications for multi-threat medical
      countermeasures.
AB  - Despite the contrasts in chemistry and toxicity, for blister and nerve chemical
      warfare agents there may be some analogous proteolytic and inflammatory mediators
      and pathological pathways that can be pharmacological targets for a single-drug
      multi-threat medical countermeasure. The dermal-epidermal separation caused by
      proteases and bullous diseases compared with that observed following exposure to
      the blister agent sulfur mustard (2,2'-dichlorodiethyl sulfide) has fostered the
      hypothesis that sulfur mustard vesication involves proteolysis and inflammation.
      In conjunction with the paramount toxicological event of cholinergic crisis that
      causes acute toxicity and precipitates neuronal degeneration, both anaphylactoid
      reactions and pathological proteolytic activity have been reported in nerve-agent
      intoxicated animals. Two classes of drugs already have demonstrated multi-threat
      activity for both nerve and blister agents. Serine protease inhibitors can
      prolong the survival of animals intoxicated with the nerve agent soman and can
      also protect against vesication caused by the blister agent sulfur mustard. Poly
      (ADP-ribose) polymerase (PARP) inhibitors can reduce both soman-induced neuronal
      degeneration and sulfur-mustard-induced epidermal necrosis. Protease and PARP
      inhibitors, like many of the other countermeasures for blister and nerve agents,
      have potent primary or secondary anti-inflammatory pharmacology. Accordingly, we
      hypothesize that drugs with anti-inflammatory actions against either nerve or
      blister agent might also display multi-threat efficacy for the inflammatory
      pathogenesis of both classes of chemical warfare agent.

PMID- 12794940
TI  - Life history parameters of the two-spotted spider mite (Tetranychus urticae Koch)
      feeding on bean leaves treated with pyrrolizidine alkaloids.
AB  - In this study we assess the effect of pyrrolizidine alkaloids (PAs) extracted
      from Lithospermum canescens on the biology of the two-spotted spider mite
      (Tetranychus urticae Koch). Lithospermum canenscens (Michaux) Lehm.
      (Boraginaceae) is a common prairie plant also known as Indian paint or hoary
      puccoon. A mixture of seven PAs with known chemical structures was used in this
      investigation. Mites treated with PAs showed a high mortality of juveniles, a
      decrease in female fecundity and a shortened longevity. The intrinsic rate of
      population increase (r(m)) was used as an indicator of T. urticae population
      performance after treatment with PAs. The r(m) value obtained with alkaloid
      treated leaves was lower than that for mites developing on untreated leaves,
      which indicates that the mite population would develop much slower on treated
      plants. The results suggest that further studies should be performed to assess
      the possible use of PA extracts for spider mite control.

PMID- 12794941
TI  - Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: modulatory
      effects of alpha- and gamma-tocopherol.
AB  - Cholesterol can be oxidized to form a variety of cholesterol oxidation products
      also known as oxysterols. The aims of the present study were to compare the
      cytotoxic effects of four oxysterols, namely 25-hydroxycholesterol (25-OHC),
      7beta-hydroxycholesterol (7beta-OHC), cholesterol-5beta,6beta-epoxide (beta-epox)
      and cholesterol-5alpha,6alpha-epoxide (alpha-epox), in two human cell culture
      models. Further, the ability of 10 and 100 micro m alpha- and gamma-tocopherol
      (alpha-TOC and gamma-TOC, respectively) to protect against oxysterol-induced
      cytotoxicity was also assessed. Human colonic adenocarcinoma Caco-2 and human
      hepatoma HepG2 cells were supplemented with increasing concentrations of 25-OHC,
      7beta-OHC, beta-epox and alpha-epox (0-25 micro g ml(-1)) for 24, 48 or 96 h.
      Following 24-h and 48-h exposure, test media were replaced with normal growth
      media and the cells were maintained for 72 and 48 h, respectively. The 96-h
      exposure represented a constant challenge to the cells. Cytotoxicity was assessed
      using the neutral red uptake assay. The concentration of compound that inhibited
      cell viability by 50% (ic(50) value) was calculated. All four oxysterols
      investigated induced the greatest cytotoxic effects following 96 h of exposure.
      25-Hydroxycholesterol exhibited the greatest cytotoxicity in both cell lines.
      Both beta-epox and alpha-epox were more toxic to HepG2 cells than to Caco-2 cells
      after the 48-h exposure. Pretreatment of cells with either alpha- or gamma-TOC
      did not protect against oxysterol-induced cytotoxicity. The caco-2 cells treated
      with the high concentration (100 micro m) of gamma-TOC were found to be more
      susceptible to oxysterol-induced toxicity under the conditions employed in this
      study.

PMID- 12794942
TI  - Research fraud, public policy, and gun control.

PMID- 12794943
TI  - The cognitive context of historical change: assimilation, accommodation, and the
      segmentation of competence.

PMID- 12794944
TI  - Cognition, development, and cultural practices.

PMID- 12794946
TI  - Divergent cultural models of child rearing and pedagogy in Japanese preschools.

PMID- 12794945
TI  - Cultural change and human development.

PMID- 12794947
TI  - Conflict, social development, and cultural change.

PMID- 12794948
TI  - Neighborhood rhythms and the social activities of adolescent mothers.

PMID- 12794949
TI  - Ups and downs: daily cycles of adolescent moods.

PMID- 12794950
TI  - Waiting for the weekend: Friday and Saturday night as the emotional climax of the
      week.

PMID- 12794951
TI  - Weekly rhythms of parents' work stress, home stress, and parent-adolescent
      tension.

PMID- 12794952
TI  - Seasonal and weekly rhythms: windows into variability in family socialization
      experiences in early adolescence.

PMID- 12794953
TI  - Implications for policy and practice: getting adolescents, families, and
      communities in sync.

PMID- 12794954
TI  - Getting our bearings in life.

PMID- 12794955
TI  - Giving birth. Voices of Chinese women.
AB  - The meaning of the childbirth experience for Chinese women living in the People's
      Republic of China is described in this phenomenological study. Ten primiparous
      women participated in audiotaped interviews within 5 months of giving birth, 9
      from Beijing and 1 from Chongqing. The interviews were translated by a bilingual
      native Chinese speaker and transcribed by the researcher. Themes were identified
      from the rich narrative data, including the One Child Policy's influence on
      childbearing, the transition to motherhood, and the influence of the cultural
      practice of "doing the month" (zuo yue zi). The findings provide insights into
      how nurses can provide better nursing care by learning about and validating
      specific cultural practices related to childbearing. The rising number of Chinese
      immigrants to the United States reflects the increasing need for more culturally
      competent care by nurses to ensure positive perinatal health outcomes.

PMID- 12794956
TI  - Spirituality in caregivers of family members with dementia.
AB  - Caring for a loved one with dementia is a difficult and stressful task due to the
      multiple memory and behavior problems that persist over many years. Researchers
      have implemented various intervention strategies and evaluated their impact on
      the negative aspects of caregiving. Yet, many of these strategies have failed to
      show reductions in the burden of caregiving. However, caregivers sometimes report
      that these same intervention strategies were extremely helpful. Perhaps those
      strategies are helping caregivers find spiritual meaning in their lives that
      empowers them to transcend their caregiving difficulties. Thus, the purpose of
      this study is to investigate spiritual meaning in caregivers of family members
      with dementia. A descriptive, naturalistic field study using qualitative
      interviewing techniques was used to collect data from 9 family caregivers of
      adults with dementia. In this study, spirituality was described as a connection
      between a higher power, others, and oneself that resulted from patterns of
      process, communication, and discovery.

PMID- 12794957
TI  - A phenomenological pilot study of the nurses' experience providing spiritual
      care.
AB  - The purpose of this phenomenological pilot study was to describe the experience
      that nurses have in providing spiritual care to their patients and/or patients'
      family members. Three nurses with a variety of clinical backgrounds were
      interviewed to elicit their experience of providing spiritual care. The data were
      analyzed using Colaizzi's method to reveal seven themes: the spiritual nurse,
      capturing the elusive and abstract nature of spirituality, the nurse-client
      spiritual journey, opening the doors for the spiritual journey, choosing to be
      silent, the nurse as a role model for spiritual behaviors, and reaping the
      benefits of spiritual care. Limitations and implications of the findings are
      discussed.

PMID- 12794958
TI  - Buddhism, behavior change, and OCD.
AB  - For individuals with obsessive compulsive disorder (OCD), the difficulty of their
      situation comes as no surprise. But what might be less expected is how directly
      their situation is spoken to in Buddhist teachings. Still, in nearly all
      mainstream discussions of psychiatric disorders, including OCD, the rich
      philosophical and spiritual dimensions of these conditions and the related
      treatment and care tend to be either ignored or disguised in euphemisms and vague
      explanations. This article sheds light on this hidden aspect of psychiatry and
      psychiatric nursing through a philosophical analysis of one of the most popular
      approaches to treating OCD, Schwartz's four-step method from Brain Lock. In so
      doing, the argument is made that sharing the philosophical and spiritual
      foundations of treatment and care promises not only to deepen the insights and
      skills of clinicians but also to empower clients as participants in their own
      journeys toward wellness and beyond.

PMID- 12794959
TI  - A behavioral-medicine program in HIV. Implications for quality of life.
AB  - The purpose of this descriptive study is to examine quality of life issues in
      participants in a behavioral-medicine group (N = 24). Of the sample, 60%
      indicated current use of complementary therapies. Sexual functioning, a subscale
      of the quality-of-life measure, was positively correlated with length of time
      with HIV. CD4+ lymphocyte counts were not significantly correlated with quality
      of life (QOL). Viral load (VL) was positively correlated with the social-support
      subscale of the QOL scale. Use of body therapies (massage, acupuncture) was
      associated with social functioning and use of nutritional therapies was
      associated with mental health. Results of the study indicate that clinical
      interventions, including behavioral-medicine interventions and complementary
      therapies for persons with HIV/AIDS, can result in greater QOL.

PMID- 12794961
TI  - Diffusion and dissemination of evidence-based cancer control interventions.

PMID- 12794960
TI  - Using reflexology for pain management. A review.
AB  - More than two thirds of Americans with chronic pain are now using complementary
      and alternative therapies. One complementary and alternative therapy,
      reflexology, has a long history and has been found useful on a case-by-case
      basis. This article provides a review of the literature on the use of reflexology
      as a therapy in pain management. Although reflexology is widely used, systematic
      research is needed to examine its effectiveness. To date, however, only a few
      studies have focused on reflexology's use in pain management. Because reflexology
      is a noninvasive, nonpharmacological therapy, nurses are in a position to do
      research on and make decisions about its clinical effectiveness.

PMID- 12794962
TI  - Daubert, cognitive malingering, and test accuracy.
AB  - Daubert v. Merrell Dow Pharmaceuticals (1993) held that trial judges should
      permit expert scientific testimony only when "the reasoning or methodology
      underlying the testimony is scientifically valid, and ... properly can be applied
      to the facts in issue." Vallabhajosula and van Gorp ("V & vG," 2001) have
      suggested that when the Daubert standard is applied to tests for malingered
      cognitive deficits, courts should deem admissible only results that meet this
      mathematical standard: assuming a pretest probability of .3, a "positive" score
      on the malingering test should yield a posttest probability of at least .8. This
      paper shows that V & vG's criterion may lead to misunderstandings about the kind
      of information maligering measures provide. After reviewing cases that have
      discussed both the Daubert decision and malingered cognitive deficits, this paper
      uses data from the Test of Memory Malingering (T.N. Tombaugh, 1996) to provide a
      general characterization of the mathematical properties of malingering measures.
      The paper then describes how pretest knowledge about malingering is combined with
      knowledge about a test's performance to generate a posttest probability of
      malingering. The results can help mental health experts respond to Daubert
      inspired challenges to conclusions based on malingering measures.

PMID- 12794963
TI  - Recidivism in stalking and obsessional harassment.
AB  - Despite the rapidly growth of mental health attention focused on the phenomenon
      of stalking, no empirical research to date has attempted to assess the frequency
      of repeat offending or attempted to identify predictors of recidivism. A total of
      148 stalking and harassment offenders who were court-ordered to undergo a mental
      health evaluation were followed for a period of 2.5-13 years in order to assess
      the frequency of repeat offenses and the variables that differentiated high
      versus low risk offenders. Recidivism data were obtained from a variety of
      sources, including criminal justice records, mental health records, and reports
      from probation officers and victims. A number of potential "predictor" variables
      were selected on the basis of the existing recidivism literature in other
      criminal justice populations. Frequency analysis were used to identify variables
      that significantly differentiated offenders who did and did not reoffened while
      survival analysis was used to analyze the impact of these covariates on time to
      reoffense. A total of 49% of the offenders reoffended during the follow-up
      period, 80% of whom reoffended during the first year. The strongest predictors of
      recidivism included the presence of a personality disorder, and in particular, a
      "Cluster B" personality disorder (i.e., antisocial, borderline, and/or
      narcissistic). In addition, those offenders with both a personality disorder and
      a history of substance abuse were significantly more likely to reoffened compared
      to either of these risk factors alone. Surprisingly, the presence of a delusional
      disorder (e.g., erotomania) was associated with a lower risk of reoffender. The
      findings are discussed in terms of the legal system and treatment implications.

PMID- 12794964
TI  - Stealing thunder as a courtroom tactic revisited: processes and boundaries.
AB  - Stealing thunder refers to a dissuasion tactic in which an individual reveals
      potentially incriminating evidence first, for the purpose of reducing its
      negative impact on an evaluative audience. We examined whether it was necessary
      to frame the negative revelation in a manner that downplayed its importance, and
      found that stealing thunder successfully dissuaded mock jurors even without
      framing. We also sought to determine the mechanism by which stealing thunder
      operated, and found that stealing thunder led mock jurors to change the meaning
      of incriminating evidence to be less damaging to the individual. We also found
      that stealing thunder's effectiveness did not hinge on whether or not opposing
      counsel also mentioned the thunder evidence, and that the stealing thunder tactic
      was no longer effective when opposing counsel revealed to the mock jurors that
      the stealing thunder tactic had been used on them.

PMID- 12794965
TI  - Elevated risk of arrest for Veteran's Administration behavioral health service
      recipients in four Florida counties.
AB  - This paper examines the relative contribution of mental and substance abuse
      disorders to criminal justice involvement by examining the relative risk of
      arrest for three groups of adult male recipients of VA behavioral health care
      services. These groups include men served for both substance abuse and mental
      health, for only substance abuse, and for only mental health. The relative risk
      of multiple offences is compared to relative risk of a single offense for each
      group. Results indicated that relative risk of multiple arrests for the dual
      diagnosis group is substantially greater than for either of the single diagnosis
      groups, and greater than the relative risk for recipients of nonbehavioral health
      services. Relative risk of arrest for recipients of only mental health services
      is no different than the relative risk for other veterans living in the region
      under examination.

PMID- 12794966
TI  - Adolescents with psychopathic characteristics in a substance abusing cohort:
      treatment process and outcomes.
AB  - Psychopathy is a condition with important consequences both for individuals who
      experience it and for the communities in which they live. Although the assessment
      of psychopathy among adolescents remains controversial, some evidence suggests
      that the affective and behavioral traits of adult psychopathy begin to emerge in
      childhood (B. B. Lahey & A. Kazdin, 1990) and continue across the lifespan (A. E.
      Forth, S. D. Hart, & R. D. Hare, 1990). The present study used the Psychopathy
      Checklist: Youth Version (PCL:YV; A. E. Forth, S. D. Kosson, & R. D. Hare, in
      press) to retrospectively assess psychopathic characteristics, treatment process,
      and outcomes of 64 individuals referred for treatment to a substance abuse
      program for adjudicated adolescents. This study focused on the relationship
      between psychopathic characteristics and treatment process and outcome variables,
      including attrition rates, quality of participation, substance use throughout
      treatment, clinical improvement, and 12-month recidivism rates. Psychopathic
      characteristics were negatively related to treatment process and outcome
      variables, including attrition, participation, substance use, and clinical
      improvement. Psychopathic characteristics were positively related to the number
      of arrests in the 12 months following treatment completion. Implications for
      treatment and future research with adolescents displaying psychopathic
      characteristics are discussed.

PMID- 12794967
TI  - Extra effort during memory retrieval may be associated with increases in
      eyewitness confidence.
AB  - When testifying in court, witnesses are motivated to try as hard as possible to
      give an accurate account. This study tested the proposition that extra effort by
      eyewitnesses during a memory test can lead to higher confidence ratings without
      any accompanying changes in accuracy. Participant-witnesses answered multiple
      choice questions about a classroom visitor who had spoken 5 days earlier. In the
      high-motivation condition participants could earn prizes based on their memory
      test performance; in the low-motivation condition there were no special
      incentives. Although the motivation manipulation did not affect mean witness
      confidence, the confidence-accuracy and effort-accuracy correlations were
      substantially smaller in the high-motivation condition than in the low-motivation
      condition. Furthermore, the confidence ratings for those participants who
      reported expending high levels of effort in both motivation conditions were
      significantly higher than the confidence ratings for the low-effort participants,
      despite the fact that response accuracy did not differ as a function of reported
      effort. These findings have important implications for understanding how
      pressures to perform well in the courtroom can affect eyewitness confidence.

PMID- 12794968
TI  - Cluster of severe acute respiratory syndrome cases among protected health care
      workers-Toronto, April 2003.

PMID- 12794969
TI  - Modelling the costs and effects of a universal infant immunization program using
      conjugated pneumococcal vaccine in British Columbia.

PMID- 12794970
TI  - Consigned to the foothills.

PMID- 12794972
TI  - Net gains for health.

PMID- 12794971
TI  - Beating the odds.

PMID- 12794974
TI  - Keeping a roof over our heads.

PMID- 12794973
TI  - HRT for men? I don't believe it.

PMID- 12794976
TI  - Slowly but surely.

PMID- 12794975
TI  - Pick and mix.

PMID- 12794977
TI  - Lost realities.

PMID- 12794978
TI  - Self-esteem and audit feedback.
AB  - BACKGROUND: Audits of clinical practice are regularly carried out in healthcare
      settings (NHSE 1996). As part of the audit process, results are fed back to the
      senior nurse or manager in the audit area, often in written form. CONCLUSION:
      This method of feedback has benefits for the person giving the audit results as
      it is a standardised method and less time-consuming. However, clinical staff need
      the opportunity to discuss the problems identified, if motivation is to be
      improved. There is also little benefit if feedback comments focus on what needs
      to be improved without looking at positive points. Some types of audit feedback
      can provide destructive criticism, which may have an adverse effect on nurses'
      self-esteem. It should, however, be possible to adapt the way that feedback is
      given following audit to improve self-esteem and motivation.

PMID- 12794979
TI  - Difficulties in clinical supervision and lifelong learning.
AB  - Reflective and lifelong learning are integral components of professional
      practice. They have been introduced successfully in nursing as part of academic
      study programmes, but nurses have been less keen to embrace the facilitated
      reflection on practice known as clinical supervision, despite professional
      requirements to do so. This article explores the context in which clinical
      supervision resides, and the parallels of policy issues with post-compulsory
      education and training. The focus is on lifelong learning. The aim is to identify
      an implementation strategy by exploring the difficulties in implementing clinical
      supervision and lifelong learning through critical analysis. The objective is to
      determine how to remove these barriers. Derivative themes underpin
      recommendations for practice in the conclusion. The themes are: Careful planning
      of objectives and goals. Working more creatively through the use of technology.
      Using existing forums. Networking with other disciplines.

PMID- 12794981
TI  - Majority rule.

PMID- 12794980
TI  - Atrial fibrillation: Part 1.
AB  - Part 1 of this two-part article on atrial fibrillation--a common cardiac rhythm
      abnormality--covers the mechanical and electrical functions of the heart. It also
      looks at cardiac monitoring and rhythm interpretation. Part two, published in
      next week's Nursing Standard, will discuss the predisposing factors,
      investigations and methods of treatment.

PMID- 12794982
TI  - Hot and bothered.

PMID- 12794983
TI  - The HSJ interview: Professor Sir Ara Darzi. Just the ticket. Interview by Nick
      Edwards.

PMID- 12794984
TI  - HSJ Awards 2003. Vote of confidence.

PMID- 12794985
TI  - Patient involvement. Complain and simple.
AB  - Complainants have been involved in designing a new system for addressing and
      preventing patient concerns. Many have become volunteer members of patient
      involvement groups. Formal and Informal complaints have dropped significantly in
      the past two years. Addressing issues when 'they are going wrong, rather than
      have gone wrong' has been emphasised.

PMID- 12794987
TI  - My brilliant career-human resources. Life at a gallop. Interview by Nick Edwards.

PMID- 12794986
TI  - Nursing grades. In the frame.
AB  - Competency-based frameworks were developed to cover community nursing, school
      nursing and health visitors, to improve retention and working methods. It
      identified large variations between organisations and in nurses' ability to
      progress their careers. The frameworks are run by all six PCTs in the area and
      cover grades A to H.

PMID- 12794988
TI  - HSJ people. Appraisal be.

PMID- 12794989
TI  - Water purification system assessed.

PMID- 12794990
TI  - Avoiding spread of airborne infections.

PMID- 12794991
TI  - Handling exceptional events.

PMID- 12794992
TI  - Correct attitude is vital.

PMID- 12794993
TI  - Implications of change noted in The Netherlands.

PMID- 12794994
TI  - Countries compared.

PMID- 12794995
TI  - Meeting thermal insulation requirements.

PMID- 12794996
TI  - Spotlight on oxygen needs.

PMID- 12794998
TI  - [Open champion for deinstitutionalization, homage to Lucien Bonnafe].

PMID- 12794999
TI  - [Reactions to the creation of a health director corps].

PMID- 12795001
TI  - [Dreaming of liberty].

PMID- 12795002
TI  - [Psychiatric nurses talk to each other at the Serpsy forum].

PMID- 12795003
TI  - [Between yesterday and today, something has changed].

PMID- 12795004
TI  - [Swan-song or the chronicle of the announced death of the sector].

PMID- 12795005
TI  - [Seeds in psychiatry].

PMID- 12795006
TI  - [A specialized program for management of patients with bipolar disorders].

PMID- 12795007
TI  - [Nursing care and relationship with the patient's family 1/2].

PMID- 12795008
TI  - [Psychotropic agents. 7/7 Anticonvulsants].

PMID- 12795009
TI  - Faecal incontinence after vaginal delivery.

PMID- 12795010
TI  - Feasibility of using paper impregnated with urine instead of liquid urine for
      assessing ovarian activity.
AB  - BACKGROUND: Ovarian activity should ideally be assessed by serial non-invasive
      methods that require simple procedures for sample collection and storage.
      Measurement of urinary oestrone-3-glucuronide and pregnanediol-3 alpha
      glucuronide is a non-invasive method available for assessment of ovarian
      activity, but transport of large numbers of urine samples is cumbersome and
      samples need to be stored frozen. An alternative sample collection, transport and
      storage procedure that is easier to handle and requires no or minimal cold
      storage facilities will particularly benefit studies in which ovulatory activity
      needs to be assessed in field settings. OBJECTIVE: To evaluate the feasibility of
      using paper impregnated with urine as an alternative to liquid urine for the
      measurement of oestrone-3-glucuronide and pregnanediol-3 alpha-glucuronide
      concentrations in the assessment of ovarian activity. METHODS: Urine samples
      collected daily throughout regular menstrual cycles were stored as liquid urine
      at -20 degrees C, and as paper impregnated with urine, in the refrigerator for 3
      to 12 months or at room temperature for 1 to 6 months. Oestrone-3-glucuronide and
      pregnanediol-3 alpha-glucuronide concentrations were measured in these urine
      samples by enzyme immunoassay. Values obtained were correlated using Spearman's
      correlation test. RESULTS: The pattern of oestrone-3 glucuronide and pregnanediol
      3 alpha-glucuronide concentrations estimated using paper impregnated with urine
      followed that of liquid urine in all storage conditions used. Values obtained by
      two methods correlated significantly (p < 0.001 to 0.0001) though the paper
      impregnated with urine gave slightly higher values. CONCLUSIONS: Paper
      impregnated with urine can be used to facilitate sample collection, transport and
      storage of urine when oestrone-3-glucuronide and pregnanediol-3 alpha-glucuronide
      measurements are required in a large number of serial samples to assess ovarian
      activity.

PMID- 12795011
TI  - Revascularisation in diabetic "small vessel disease" of lower limbs: is it
      worthwhile?
AB  - BACKGROUND: Diabetic patients with critical ischaemia of the lower limb despite a
      palpable popliteal pulse are presumed to have 'small vessel disease' that is
      unreconstructable and often subjected to major amputation. Results of
      revascularisation in such patients are presented. METHODS: A prospective
      observational study of revascularisation [n = 23, 14 men, mean age 62 years
      (range 47 to 80)] using saphenous vein to bypass occluded infrapopliteal arteries
      in diabetics with critical leg ischaemia over a 5-year period. OUTCOME MEASURES:
      Surgical mortality, graft patency, major amputation rate, time taken for healing,
      ambulation after discharge from hospital. RESULTS: There was one death within 30
      days of surgery. 2/4 early thromboses were salvaged, 5 (5/22) limbs were
      amputated. Limb salvage was 17/23 (74%). Two limbs were amputated because of
      thrombosis and 3 were amputated for spreading sepsis despite a patent graft. 2
      late graft failures were detected but the limbs remain healed and functional.
      15/23 (65%) re-vascularisations remained patent at a mean follow up of 30 months
      (range 4 to 60). Mean wound healing time was 30 days (range 16 to 45). 14/17
      (82%) of those with salvaged limbs were independent with regard to ambulation.
      CONCLUSION: Bypass of diabetic small vessel disease of the lower limbs is
      feasible and effective in preventing major amputation and maintaining independent
      mobility.

PMID- 12795012
TI  - Clinical features, risk factors and efficacy of cryotherapy in cutaneous
      leishmaniasis in Sri Lanka.
AB  - INTRODUCTION: The first autochthonus case of cutaneous leishmaniasis in Sri Lanka
      was reported in 1992. Several case reports from different parts of the island
      have been documented. The case incidence has increased in the recent past.
      OBJECTIVES: To determine the clinical patterns, risk factors and efficacy of
      cryotherapy for cutaneous leishmaniasis in Sri Lanka. PATIENTS: Sixty-five
      patients with cutaneous leishmaniasis. DESIGN: Prospective study. SETTING:
      Department of Parasitology, Faculty of Medicine, Colombo. METHODS: Direct smears
      prepared from lesion aspirates or punch biopsies were stained and examined for
      Leishmania sp. All patients with positive smears were included in the study. A
      pre-designed questionnaire was completed based on clinical evaluation, and the
      patients were treated and followed up regularly. Investigations were repeated on
      day 14 and day 90 depending on the response to treatment. RESULTS: Lesions were
      non-tender, non-itchy papules (early lesions), scaling single nodules or dry
      crust forming single or multiple ulcers. Young adult males with outdoor
      behavioural characteristics were mostly affected. Other risk factors were close
      proximity to jungles, potential reservoir hosts in the environment, lack of
      awareness and inadequate knowledge and use of preventive measures. Compliance
      rate for cryotherapy was 40%. The need for frequent hospital visits, the long
      course of treatment, limited availability and undesirable side effects were
      identified as reasons for poor compliance. Smear positive rate on day 14 after
      treatment was 89%. CONCLUSIONS: Cutaneous leishmaniasis is now an established
      disease in Sri Lanka. Raising public awareness, early diagnosis, definite species
      identification, availability of proper treatment methods and vector studies are
      important for its effective control.

PMID- 12795013
TI  - Clinical examination in paediatrics at final MBBS: views of children and their
      parents.
AB  - INTRODUCTION: The final examination in paediatrics for medical undergraduates in
      Sri Lanka consists of a written and a clinical component. Each candidate at the
      clinical component sees one long case and two short cases. OBJECTIVES: To assess
      the views of the bystanders regarding their sick children participating at a
      clinical examination, and to evaluate the children's perceptions of the clinical
      component. METHODS: An interviewer-administered questionnaire was discussed
      separately with the participating children and their bystanders at the final year
      examination in paediatrics of the Faculty of Medicine, Colombo, in 1999. RESULTS:
      116 patients participated at the clinical examination in paediatrics. 107 (92%)
      of the bystanders were the children's mothers. Informed consent had not been
      obtained for use in the examination from 59 (51%) of the children's mothers.
      Seven (6%) were not satisfied with the way their children were handled by the
      candidates, and 25 (21.5%) showed concern about the number of candidates
      examining their child. Bystanders who participated at the long cases were
      inconvenience more than those in the short cases. 34 children above the age of 5
      years were also interviewed. An explanation regarding the examination had not
      been given to 31 (92%) of them. Six children (17%) said they were examined for
      too long. A majority of the bystanders welcomed the payments received and all of
      them were satisfied with the medical students' conduct and politeness. All of
      them agreed that this form of clinical examination was a good method of
      evaluating a student's professional competence. CONCLUSIONS: Several aspects of
      the clinical component of the final examination in paediatrics for medical
      undergraduates need to be improved to minimise the inconvenience experienced by
      the children and their parents.

PMID- 12795014
TI  - Microbiology of cerebral abscess at the neurosurgical unit of the National
      Hospital of Sri Lanka.
AB  - OBJECTIVES: To determine the microbial pathogens responsible for cerebral
      abscess, ascertain the most suitable antibiotic for treatment and to determine
      the predisposing causes of cerebral abscess. DESIGN: Prospective study with
      microbiological investigation of pus aspirated from cerebral abscesses. SETTING:
      Neurosurgical Unit, National Hospital of Sri Lanka, Colombo. STUDY GROUP: 41
      patients with cerebral abscess. PERIOD OF STUDY: 18 months (May 1997 to December
      1998) RESULTS: Of the 41 samples of pus 26 (63.1%) gave a positive microbial
      culture. The Gram stain of the direct smear was positive in 77% of the 26
      positive cultures. The most frequently occurring species were Streptococcus
      milleri group (35%) followed by Staphylococcus aureus (10%). Anaerobes accounted
      for 23% of positive cultures. All Streptococcus milleri isolates were penicillin
      and cefotaxime, and all anaerobic isolates except one were susceptible to
      sensitive to metronidazole. 75% of Gram negative bacilli isolated were sensitive
      to cefotaxime. All Staphylococcus aureus isolates were methicillin resistant, but
      sensitive to vancomycin and chloramphenicol. Common predisposing conditions were
      congenital heart disease (30%), trauma (25%), middle ear disease (7%), and
      meningitis (7%). CONCLUSIONS: Organisms of the Streptococcus milleri group were
      most frequently found in cerebral abscesses. The present empirical therapeutic
      regime adopted in the unit which consisted of cefotaxime 1 g intravenously three
      times daily and metronidazole 500 mg intravenously three times daily was found to
      be satisfactory as a majority of the organisms isolated were sensitive to these
      antimicrobials. In the case of methicillin resistant Staphylococcus aureus
      (MRSA), it is recommended that chloramphenicol be added to the current regime in
      management until the antibiotic sensitivity pattern is available.

PMID- 12795015
TI  - A novel reverse transcriptase-polymerase chain reaction based-liquid
      hybridisation (RT-PCR-LH) assay for early diagnosis of dengue infection.
AB  - BACKGROUND: Early definitive laboratory diagnosis of dengue is difficult with the
      tests in routine use at present. OBJECTIVE: To develop a reverse transcriptase
      polymerase chain reaction based liquid hybridisation (RT-PCR-LH) technique for
      the rapid and early diagnosis of dengue. RESEARCH DESIGN: RT-PCR products of the
      NS3 gene of dengue virus prototypes and of a few positive sera for dengue virus
      by culture, were allowed to hybridise in liquid phase with a mixture of dengue
      specific radiolabelled oligonucleotides. The products were separated by PAGE and
      visualised by autoradiography. 78 suspected dengue sera were also tested by RT
      PCR-LH method, and by IgM-ELISA and HAI tests, for comparison. RESULTS: Two DNA
      bands (approximately equal to 470 bp and approximately equal to 455 bp) specific
      to dengue virus, were observed. RT-PCR-LH assay takes only 24 h. Of the 78
      suspected dengue acute sera tested, 45/78 were positive by RT-PCR-LH, 31/78 were
      positive by IgM-ELISA, and 14/78 had a HAI titre > or = 2560. Duration of fever
      was known in 72 cases, and infection was detected by RT-PCR-LH in 11/22 of cases
      with < 5 d fever and by IgM-ELISA in 1/22. In cases with 5 to 15 d fever RT-PCR
      LH and IgM-ELISA/HAI titre > or = 2560 detected infection in 30/50 and 27/50
      respectively. The 10 sera which were negative by RT-PCR-LH, but were positive by
      either IgM-ELISA or HAI titre > or = 2560 were all > 5 d fever cases. RT-PCR-LH
      together with IgM-ELISA were capable of detecting dengue infection in 56/78 of
      the suspected cases. CONCLUSION: RT-PCR-LH assay developed in this study appears
      to have an advantage over other diagnostic techniques for the early detection of
      dengue.

PMID- 12795016
TI  - Poisoning with "hondala" leaves due to misidentification as "passion fruit"
      leaves.

PMID- 12795017
TI  - Diagnosis of adrenal myelolipoma by imaging and guided biopsy.
AB  - Adrenal myelolipoma is a rare, benign, endocrinologically inactive, and
      asymptomatic tumour which is usually found incidentally at imaging or autopsy.
      Symptomatic tumours are very rare. We describe a case of adrenal myelolipoma
      where the diagnosis was made on the basis of radiological features and image
      guided fine needle biopsy, without resorting to an operation.

PMID- 12795018
TI  - Fatal septicaemia caused by Chromobacterium violaceum.
AB  - We report a case of Chromobacterium violaceum septicaemia in a 10-year old boy
      admitted to hospital in September 2001, two weeks after he suffered a crush
      injury of the left foot. In spite of surgical debridement and antibiotics his
      condition worsened and he developed multiple liver and lung abscesses. He died
      one week after admission and a blood culture grew Chromobacterium violaceum.

PMID- 12795019
TI  - An unusual cause of melaena in a child.

PMID- 12795020
TI  - Isolated ventricular non-compaction or 'spongy cardiomyopathy'.

PMID- 12795021
TI  - Efficacy of a five-day course of primaquine in preventing relapses in Plasmodium
      vivax malaria--a pilot study.

PMID- 12795023
TI  - A case of chyluria.

PMID- 12795022
TI  - Cytomegalovirus induced haemophagocytic syndrome.

PMID- 12795024
TI  - The adolescent girl.

PMID- 12795025
TI  - [Oral antidiabetic therapy and cardiovascular complications: theoretical problem
      or clinical evidence?].
AB  - Theoretical and experimental research data as well as human epidemiological
      studies on large populations suggest a great difference in influencing
      cardiovascular processes and alterations among the oral antidiabetic drugs used
      in the treatment of type II diabetes mellitus. Drugs delaying or inhibiting
      carbohydrate absorption as well as insulin sensitizers have an unambiguous
      reducing effect on diabetic cardiovascular complications. Only fluid retention
      needs precaution during the treatment with thiazolidinedions in patients
      suffering from heart disease. Among insulin secretizers repaglinid, glibenclamid
      and glipizide have an ATP-sensitive potassium channel inhibiting effect in the
      vascular smooth muscle cells, too, reducing hereby vasodilation. Glibenclamide
      also inhibits ischaemic preconditioning. Therefore, the antidiabetic drug of
      choice can be decisive in diabetic patients suffering from ischaemic heart
      diseases or peripheral obliterative disorders. In the case of secondary
      sulphonylurea resistance and/or severe ischaemic alterations insulin treatment
      becomes necessary to avoid further cardiovascular complications.

PMID- 12795026
TI  - [Premeditated ecstasy?].
AB  - The 3-4-methylene-dioxy-methamphetamine, or "Ecstasy" is one of the most
      preferred, illicite recreational drugs in Hungary also. Its effects are basically
      the same as of the amphetamine's effects,--i.e., central nervous system's and
      cardiovascular effects. The most important ones are different disturbances in the
      serotonin and dopamine metabolism, particularly in the CNS. Moreover, under
      Ecstasy's effect there can be encountered different toxic signs and symptoms as
      well, e.g. effect on the temperature regulation,--which may require
      hospitalization. In spite of the users' tenet,--that the drug is a "safe" one,-
      it is evident that Ecstasy has late effects as well,--for example a single dose
      may induce Parkinson's like symptoms. Taking into consideration the above
      mentioned facts, it can be stated un ambiguously that Ecstasy's use should be
      banned. It is harmful not only to the individual users but to the whole society
      as well.

PMID- 12795027
TI  - [Esophageal and gastrointestinal application of traditional and metal
      prostheses].
AB  - INTRODUCTION: The endoscopic prosthesis implantation in malignant oesophago
      gastrointestinal stenoses is an important palliative therapeutic method. Even
      with traditional prosthesis placement in the last 10 years the application of
      metal prosthesis is more and more frequent. PATIENTS AND METHODS: In this article
      the authors summarise their experiences with traditional and metal prosthesis
      implantations between September of 1991 and November of 2002. In the last 11
      years 180 prostheses were implanted for 152 patients. Out of these 130 were
      traditional and 50 were metal prosthesis. The traditional prostheses were
      implanted with balloon catheter introducer following dilatation up to 17-18 mm
      with balloon and Savary bougie. The metal prostheses were implanted after balloon
      catheter dilatation up to 14 mm. The cause of stenosis in 61 cases were
      inoperable or recurrent oesophageal cancer, in 45 gastric cancer, in 38 cases
      oesophageal compression or infiltration by lung cancer, mediastinal metastases
      due to breast cancer in 7 and kidney cancer in 1 case. 111 prostheses were
      implanted in to the oesophageal, 24 cardial, 3 gastro-enteral, 8 oesophago
      jejunal, 6 jejunal stenoses. RESULTS: Due to the stent implantation the patients
      average dysphagia score decreased from 2.85 (SD = 0.7) to 1.0 (SD = 0.6). From
      our patients 33 had oesophago/gastro--respiratoric/mediastinal/thoracocutaneous
      fistula. Out of these 26 were successfully closed with metal prosthesis and 5 out
      of 7 with traditional prostheses. The severe early complications with traditional
      prosthesis (5 perforation, 2 hydropneumothorax, 1 mediastinal and subcutaneous
      emphysema) were in 6.2% of the cases. From 8 patients 4 healed after drainage, 3
      following conservative therapy and 1 died. Early, severe complication, thoracic
      empyema was observed in one patient from 50 implanted metal stent. The patient
      died after surgical drainage. In 2 patients as a severe late complication with
      Wallstent, severe bleeding occurred, and in 2 patient at the funnel of a
      traditional stents, 3 esophago-tracheal fistulas developed. Furthermore there
      were stent dislocations (17/152) and stent obstructions (15/152) all together
      (32/152) in 21% of the cases. CONCLUSIONS: The implantation of traditional
      prostheses method used by the authors runs with low risks and gives good results.
      Implantation of metal stent is easier, less burden for the patient and
      considerably decreasing the risk of early, severe complications, widening the
      application territory for prostheses. In the frequency of late complication
      however there is no significant difference between the methods.

PMID- 12795028
TI  - [Effects of emedastine eyedrops on acute seasonal allergic conjunctivitis in
      children].
AB  - The developments of the symptoms of acute allergic inflammation of the
      conjunctiva (itching of the eye, conjunctival hyperaemia and oedema, and
      lacrimation) is largely due to the histamine released in the course of the
      allergic reaction. A major role in its treatment is therefore played by eyedrops
      with an antihistamine effect. The aims of the present study were to establish
      whether there is a rapid effect of eyedrops containing the selective H1 receptor
      blocker emedastine on acute seasonal allergic conjunctivitis and, if so, the time
      required for this effect to develop. Eyedrops containing emedastine were
      administered in the ragweed season to 20 children (12 boys and 8 girls) with
      acute allergic inflammation of the conjunctiva resulting from a hypersensitivity
      to ragweed pollen, the average age of the 20 children was 12.3 years (range: 5
      19). The degrees of itching of the eye and of conjunctival hyperaemia were each
      characterised on a scale ranging from 0 to 4 (4 denoting the most severe
      symptoms). It was found that, after a single administration of 1 emedastine
      eyedrop, the degree of itching of the eye fell from the starting score of 2.85 +/
      0.75 to 0.45 +/- 0.51 within an average of 2.95 minutes, while the conjunctival
      hyperaemia fell from 2.35 +/- 0.59 to 0.55 +/- 0.51 in an average of 7.7 minutes.
      The level of the improvement for both symptoms was highly significant. An
      undesirable side effect (a burning sensation on the eyeball) was observed in one
      case. It may be stated that the eyedrop containing emedastine effectively
      decreases the extents of itching of the eye and conjunctival hyperaemia in
      children with acute allergic conjunctivitis, its effects are exerted within
      minutes.

PMID- 12795029
TI  - [Hungarian physicians in Vienna: Moric Rosenthal, Jozsef Grunfeld, Sandor
      Spitzer].

PMID- 12795030
TI  - [A leading surgeon in America: Arpad Gerster (1848-1923)].

PMID- 12795031
TI  - [Dr. Ferenc Strobl (1902-1975)].

PMID- 12795032
TI  - A culture of excellence.

PMID- 12795033
TI  - Rethinking cognitive function in multiple sclerosis: a nursing perspective.
AB  - Cognitive impairment is a common problem in multiple sclerosis (MS); up to 65% of
      patients exhibit some neuropsychological dysfunction during the course of their
      disease. It is a major contributing factor to unemployment, accidents, impairment
      of daily functioning, and loss of social activity in those affected by MS. The
      areas of cognition typically impaired are memory, attention, information
      processing, executive functions, and visuospatial skills. Cognitive dysfunction
      is independent of disease duration and level of disability; cognitive decline may
      begin in the earliest stages of MS before patients become even mildly disabled.
      Structural brain imaging studies show a positive correlation between the extent
      of brain atrophy and cognitive dysfunction. Despite its prevalence in MS,
      cognitive dysfunction often goes undiagnosed or is misdiagnosed as depression,
      stress, stubbornness, lack of intelligence, or psychosis. Because nurses play
      such an important role in the care of patients with MS, they are in a position to
      identify patients with cognitive dysfunction, educate patients and their families
      on ways to cope with cognitive deficits, and counsel patients on available
      treatment options. Practical guidelines help nurses identify and care for
      cognitively impaired MS patients.

PMID- 12795034
TI  - Classic trigeminal neuralgia: a surgical perspective.
AB  - Classic trigeminal neuralgia (TN) was described as early as the first century AD,
      when treatments ranged from bloodletting to the application of poison-laden
      bandages. Current medical treatment utilizes a variety of drug therapies. Surgery
      is reserved for those who are unable to tolerate the side effects or in
      situations in which the drugs prove to be ineffective. Surgical options include
      microvascular decompression, percutaneous balloon compression, radio-frequency
      thermocoagulation, and glycerol injection. Nurses play a critical role in the
      multidisciplinary care of patients undergoing surgical procedures for TN.

PMID- 12795035
TI  - Fatigue in Myasthenia Gravis patients.
AB  - The purposes of this study were to validate psychometric properties of the
      Myasthenia Gravis Fatigue Scale (MGFS) and to use the MGFS to study the
      relationship of selected demographic and clinical variables to fatigue in a
      myasthenia gravis (MG) patient population. The MGFS, an existing scale, was
      developed to measure fatigue severity in MG patients. A convenience sample of 67
      MG patients was approached on return visit to the Neuromuscular Disease Clinic.
      After giving consent, participants filled out four questionnaires: the MGFS, the
      Chalder Fatigue Scale, the Center for Epidemiologic Studies-Depression Scale, and
      a Demographic and Clinical Data Form. Participants' muscle weakness was evaluated
      using the Modified Quantitative MG Score for Disease Severity assessment form (13
      muscles tested). Three days after the clinic visit, a copy of the MGFS was mailed
      to participants to allow retest at 5 to 7 days after initial testing. Findings
      showed that the MGFS demonstrated adequate internal consistency and test-retest
      reliability. In addition, the fatigue severity (MGFS) score correlated moderately
      with depression. We adjusted for the effect of depression and noted a
      relationship between the fatigue score and two of nine selected demographic and
      clinical characteristics--activity restriction and number of years since
      diagnosis. These results lay the groundwork for further investigation of fatigue
      in MG patients and identification of mitigating or coping methods.

PMID- 12795036
TI  - The use of individualized goal setting to facilitate behavior change in women
      with multiple sclerosis.
AB  - Setting goals is a useful strategy for changing behavior. The purpose of this
      study was to examine the effectiveness of a wellness intervention for women with
      multiple sclerosis (MS) on achieving health-related goals set individually by
      each participant in the experimental group (N = 57) using goal attainment
      scaling. The two-phase intervention included lifestyle-change classes over 8
      weeks, then telephone follow-up over 3 months. Participants were followed over an
      8-month period. Goal achievement was assessed at baseline, 2 months (following
      class), 3 1/2 months (6 weeks after class), 5 months (following 3 months of
      telephone follow-up), and at 8 months. The majority of the women met or exceeded
      all their individualized goals for changing behavior at the 6-week postclass
      assessment. Achievement and maintenance of individual goals remained high (59%
      84%) over the 5 months after class follow-ups. These data support the positive
      effects of wellness interventions for helping women with MS to meet their own
      individualized health goals. Setting goals with incremental steps helped
      participants to articulate their individual goals and monitor achievement over
      time.

PMID- 12795037
TI  - Longitudinal analysis of illness uncertainty, coping, hopefulness, and mood
      during participation in a clinical drug trial.
AB  - The purpose of this longitudinal study was to examine the relationships among
      illness uncertainty, coping effectiveness, hopefulness, and mood in persons with
      chronic, progressive multiple sclerosis (MS) during participation in a double
      blind clinical drug trial. The similarities and differences in the pattern of
      relationships among variables were investigated within each of four data
      collection time frames and across time. The convenience sample comprised 52
      participants with clinically definite MS who participated in a 2-year trial using
      methotrexate to treat progressive MS. Participants with more severe disability
      were found to be less hopeful and more emotionally distressed. Participants with
      higher levels of hopefulness used more effective coping strategies and had more
      positive moods, and those with greater uncertainty about their MS were likely to
      experience less hopefulness and more negative moods. The pattern of relationships
      among uncertainty, coping, hopefulness, and mood did not change throughout
      participation in the drug trial. The findings may be used as a foundation for
      planning nursing interventions with patients involved in drug studies.

PMID- 12795038
TI  - Presumed consent for organ procurement--does it have a future in the U.S.?
AB  - Policies of presumed consent to procure organs for transplantation have
      stimulated discussion of success/failure in increasing organ availability,
      technical pitfalls, and ethical dilemmas. The presumption of consent has made
      inroads in public policy internationally and influenced some state policies. A
      policy of presumed consent remains unlikely in the face of American attitudes of
      freedom of choice and respect for individual autonomy, but healthcare providers
      need to be aware of potential policy changes and how these changes may affect
      their practices.

PMID- 12795039
TI  - Neuroprotection for ischemic stroke.
AB  - Many pharmacological and nonpharmacologic neuroprotective therapies are in
      various phases of animal or human testing. The future in acute ischemic stroke
      therapy most likely will consist of combination therapies (Bonnono et al., 2000;
      Schellinger et al., 2001). An IV thrombolytic agent may be combined with an IA
      agent and then followed up with a neuroprotective strategy early in treatment of
      acute ischemic stroke. A hemicraniectomy may be combined with hypothermia to
      improve outcome (Georgiadis et al., 2002). Many resources (Fig 2) are available
      to assist neuroscience nurses in keeping abreast of this fast-paced area of
      development.

PMID- 12795040
TI  - Including the fathers' perspective in holistic care. Part 1: Findings on the
      fathers' experience with childhood acute lymphoblastic leukaemia.
AB  - There is scant work completed on the fathers' experience with the treatment for
      childhood cancer. The present discussion seeks to make a contribution to
      deepening our holistic understanding of paediatric treatment for leukaemia by
      presenting findings on the paternal involvement in, and experience of, treatment
      for paediatric acute lymphoblastic leukaemia (ALL). The understanding will be
      extended in Part 2 by a detailed examination of specific issues associated with
      the fathers' hospital experience and in particular, the difficulties they face
      with restraining their child-patient for treatment.

PMID- 12795041
TI  - Scientific, philosophical and social informants of holistic health care.
AB  - Concepts drawn from the broad area of non-linear dynamics including chaos and
      general systems theories have found widespread acceptance not only among health
      carers but in the broader community. These concepts are presented as partial
      informants of holistic health care. An uptake of monistic philosophy in Western
      society and changing social values are also presented as further informants of
      contemporary notions of holistic health care. Due to the diverse epistemology
      underpinning contemporary health care practice, the article concludes that
      individual concepts of holistic health care must differ markedly between health
      care practitioners who employ a holistic framework in practice.

PMID- 12795042
TI  - The use of prayer in spiritual care.
AB  - Prayer is an integral component of the spiritual life of mankind. Prayer allows
      people to express themselves during crisis and emotional turmoil. It can serve as
      an important source of personal strength and as a foundation for self-resilience
      during times of adversity. Holistic nurses may use prayer with patients to
      positively influence how patients cope with anxiety relative to illness.

PMID- 12795043
TI  - Reflexivity in nursing: where is the patient? Where is the nurse?
AB  - Drawing upon forty years of nursing experience, in this paper we are reflexive
      about four issues relative to nursing clinical practices: seeking technological
      solutions to health and ill-health; moving from the nurse-patient relationship to
      the patient-healer relationship; utilising critical pathways; and, supporting
      evidence-based nursing. We examine current nursing practices and ask probing
      questions to generate debate. Most of all, we encourage nurses to engage in
      reflexivity and not to lose sight of their selves (knowledge, expertise and
      skills), and their patients' voices and subjectivity, in their contribution to
      health care.

PMID- 12795044
TI  - Natural, complementary, alternative: which term to use?
AB  - Although natural therapies are slowly infiltrating Australian nursing practice,
      there is still no consensus over which term to use and what these terms actually
      denote and infer. This article will address these concerns to reduce the
      confusion and misperception that currently surrounds the terminology currently in
      use.

PMID- 12795045
TI  - Journey to the other side.
AB  - This paper attempts to provide a snapshot of the feelings and experience of a
      mother's journey after her son is diagnosed with cancer. It is hoped that those
      who choose to read this paper may develop some understanding of the feelings
      experienced during this frightening journey, and that this understanding may
      influence the care you give now and in the future.

PMID- 12795046
TI  - Epidemiology of non-steroidal anti-inflammatory drugs and cancer.
AB  - There is evidence that aspirin--and apparently other NSAIDs--may be protective
      agents against cancer in the gastrointestinal tract. These effects are
      particularly well documented in the colon and rectum. Even considered in
      isolation, the observational data regarding colorectal neoplasia are quite
      strong, and the reality of a protective effect is buttressed by clinical trial
      data showing that aspirin prevents sporadic adenomas. Furthermore, the NSAIDs
      sulindac celecoxib have actually led to the regression of existing colorectal
      polyps in patients with FAP. Clearly, NSAIDs have the potential to suppress
      carcinogenesis in the large bowel. Observational data suggesting inverse
      associations of NSAIDs with cancers of the stomach and esophagus have emerged
      from several case-control studies and a few cohort analyses. In some studies the
      findings display features often associated with causal relationships, for example
      decreasing risks with increasing doses or duration of use. Nonetheless, the data
      currently do not support a secure conclusion that NSAIDs protect against these
      malignancies. The relevant data are not nearly as extensive as those for the
      colorectum, and case-control investigation of these upper gastrointestinal sites
      may be particularly delicate. It is conceivable that early symptoms of cancer (or
      of pre-invasive lesions) may have discouraged NSAID use in the cancer patients,
      creating the appearance of a protective association of the drugs with the risk of
      these malignancies. More extensive observational data particularly from cohort
      studies would be desirable to confirm the existing findings and clarify the doses
      and durations of use required for an effect. Clinical trial investigation might
      also be practical for pre-neoplastic endpoints, or--in carefully selected
      populations--perhaps with cancer as the focus. There are only relatively limited
      data available regarding the effect of NSAIDs on cancer of the pancreas. However,
      the studies that have investigated this malignancy have reported indications that
      NSAIDs may have a protective effect. The effects of NSAIDs on cancers outside the
      gastrointestinal tract are not clear. Some investigations suggest that NSAID use,
      particularly aspirin, is inversely associated with risk of cancers of the breast
      or ovary, but several well-done studies have not seen these associations, and the
      observations could have been due to bias or confounding. Findings regarding
      prostate cancer are similarly conflicting. The urinary tract is one organ system
      in which several studies have reported an increased cancer risk in association
      with NSAID use. Nonetheless, the effects remain unclear. There is only limited
      available information regarding carcinoma of the bladder, and no firm conclusions
      can be drawn at this point. More extensive data have been generated regarding the
      effect of NSAIDs--largely salicylates--on renal cell carcinoma or cancer or the
      renal pelvis and ureter. Although some studies have reported increased risks,
      there are also findings suggesting no association. It is particularly difficult
      for observational studies to ascertain with confidence the true effects of
      aspirin because of the suspected relationship of these cancers with use of
      phenacetin and perhaps acetaminophen. Further data--particularly from careful and
      large cohort studies--would be important to clarify these issues. As a body of
      research, the findings discussed here from epidemiological studies and clinical
      trials have begun to clarify the effect of NSAIDs on carcinogenesis in various
      organs in humans. There is clear potential for protective effects at several
      anatomic sites. Even for the colorectum, however, it is probably premature to now
      begin to use these drugs widely for cancer prevention. To reach that point, a
      weighing of the risks and benefits of the drugs needs to be made, together with a
      judgement regarding the benefits of alternative means of prevention. For
      colorectal cancer, for example, aspirin may provide only limited benefit over
      regular colonoscopy [95, 96]. Nonetheless, with the increased understanding of
      the clinical effects of NSAIDs on cancer, the development of effective
      chemoprevention with these drugs appears to be a real possibility.

PMID- 12795047
TI  - Pharmacology of COX-2 inhibitors.

PMID- 12795048
TI  - Regulation of COX-2 expression in human cancers.

PMID- 12795049
TI  - Cyclooxygenase-2 and skin carcinogenesis.

PMID- 12795050
TI  - The role of COX-2 in breast and cervical cancer.

PMID- 12795051
TI  - Cyclooxygenase-2: a target for the prevention and treatment of cancers of the
      upper digestive tract.

PMID- 12795052
TI  - Cyclooxygenase-2 and colorectal cancer.

PMID- 12795053
TI  - Cyclooxygenase-2 in lung cancer.

PMID- 12795054
TI  - COX-2 inhibitors and other NSAIDs in bladder and prostate cancer.

PMID- 12795055
TI  - Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management
      of tumor angiogenesis.
AB  - It is clear that COX-2 plays an important role in tumor and endothelial cell
      biology. Increased expression of COX-2 occurs in multiple cells within the tumor
      microenvironment that can impact on angiogenesis. COX-2 appears to: (a) play a
      key role in the release and activity of proangiogenic proteins; (b) result in the
      production of eicosanoid products TXA2, PGI2, PGE2 that directly stimulate
      endothelial cell migration and angiogenesis in vivo, and (c) result in enhanced
      tumor cell, and possibly, vascular endothelial cell survival by upregulation of
      the antiapoptotic proteins Bcl-2 and/or activation of PI3K-Akt. Selective
      pharmacologic inhibition of COX-2 represents a viable therapeutic option for the
      treatment of malignancies. Agents that selectively inhibit COX-2 appear to be
      safe, and well tolerated suggesting that chronic treatment for angiogenesis
      inhibition is feasible [107-110]. Because these agents inhibit angiogenesis, they
      should have at least additive benefit in combination with standard chemotherapy
      [111] and radiation therapy [24, 112]. In preclinical models, a selective
      inhibitor of COX-2 was shown to potentiate the beneficial antitumor effects of
      ionizing radiation with no increase in normal tissue cytotoxicity [113-115]. More
      recently, metronomic dosing regimens of standard chemotherapeutic agents without
      extended rest periods were shown to target the microvasculature in experimental
      animal models and result in significant antitumor activity [116-118]. This
      antiangiogenic chemotherapy regimen could be enhanced by the concurrent
      administration of an angiogenesis inhibitor [116-119]. Trials that will evaluate
      continuous low dose cyclophosphamide in combination with celecoxib are underway
      in patients with metastatic renal cancer, and non-Hodgkin's lymphoma [120]. Given
      the safety and tolerability of the selective COX-2 inhibitors, and the potent
      antiangiogenic properties of these agents, the combination of antiangiogenic
      chemotherapy with a COX-2 inhibitor warrants clinical evaluation [118, 121, 122].
      The effects of selective COX-2 inhibitors on angiogenesis may also be due, in
      part, to COX-independent mechanisms [123-125]. Several reports have confirmed COX
      independent effects of celecoxib, at relatively high concentrations (50 microM),
      where apoptosis is stimulated in cells that lack both COX-1 and COX-2 [126]. More
      recently, Song et al. [127] described structural modifications to celecoxib that
      revealed no association between the COX-2 inhibitory and proapoptotic activities
      of celecoxib [125]. Some of the COX-independent mechanisms for NSAIDs and
      selective COX-2 inhibitors include activation of protein kinase G, inhibition of
      NF-kappa B activation, downregulation of the antiapoptotic protein Bcl-XL,
      inhibition of PPAR delta, and activation of PPAR gamma. One or more of these COX
      independent effects could contribute to the antiangiogenic properties of NSAIDs
      and selective COX-2 inhibitors. In order to take advantage of both the COX
      dependent and COX-independent benefits of NSAIDs and selective COX-2 inhibitors,
      will require evaluation of these agents in neoplastic disease settings, using
      cancer-specific biomarkers. In conclusion, the contribution of COX-2 at multiple
      points in the angiogenic cascade makes it an ideal target for pharmacologic
      inhibition. The reported success of selective COX-2 inhibitors in cancer
      prevention could be related to angiogenesis inhibition [109]. As premalignant
      lesions progress towards malignancy, there is a switch to the angiogenic
      phenotype that is subsequently followed by rapid tumor growth [128, 129].
      Intervention with angiogenesis inhibitors at this early stage of carcinogenesis
      has been shown to attenuate tumor growth in transgenic mouse models [130, 131].
      The continued dependence on angiogenesis for later stages of tumorigenesis
      suggests that COX-2 inhibitors also will have clinical utility in the management
      of advanced cancers.

PMID- 12795056
TI  - Potential for combined modality therapy of cyclooxygenase inhibitors and
      radiation.
AB  - In conclusion, COX-2 inhibitors have potent anti-tumorigenic activity. Results
      from animal studies strongly indicate that the likely mechanism for enhanced TGD
      and TCD50 in tumors treated with radiation and COX-2 inhibitors was the
      inhibition of angiogenesis. In our recent findings we observed that the
      antagonists of angiogenesis also inhibited the endogenous as well as phorbol
      ester-mediated induction of COX-2 expression in human lung cancer cell lines and
      that in the xenograft model a combination of angiogenic antagonists and radiation
      significantly delayed tumor growth [ASCO 2002, Vol. 21 (Part 1); p445a, #1779].
      In human tumor models, apoptosis was another mechanism of cell death.
      Furthermore, it was demonstrated that COX-2 inhibitors could change the intrinsic
      radiosensitivity of human cancer cells [41]. Therefore, inhibition of
      angiogenesis by COX-2 inhibitors may be the major mechanism for increased
      radiation effects in tumors. However, other mechanisms such as changes in tumor
      perfusion, apoptosis, and an increase in intrinsic radiation sensitivity must
      also be considered. Inhibitors of COX-2 in combination with radiation therapy may
      be an alternative strategy that can be tested in clinical trials. The combination
      of COX-2 inhibitors and radiation suggest a complementary strategy to target
      angiogenesis while potentially minimizing the impact on quality of life.
      Currently, the Radiation Therapy Oncology Group [www.rtog.org] is just one of the
      National Cancer Institute sponsored cooperative groups conducting clinical trials
      in cervix cancer, lung cancer and brain tumors, using inhibitors of COX-2 in
      combination with chemotherapy and radiation therapy. These clinical trials will
      help elucidate the role of this interesting class of agents in combination with
      cytotoxic therapy for the treatment of cancer.

PMID- 12795057
TI  - Non-steroidal anti-inflammatory and cyclooxygenase-2-selective inhibitors in
      clinical cancer prevention trials.

PMID- 12795058
TI  - Chemotherapy with cyclooxygenase-2 inhibitors in the treatment of malignant
      disease: pre-clinical rationale and preliminary results of clinical trials.

PMID- 12795060
TI  - Rotavirus vaccines, an update.

PMID- 12795061
TI  - Dracunculiasis eradication in endemic French-speaking African countries.

PMID- 12795059
TI  - Role of COX-independent targets of NSAIDs and related compounds in cancer
      prevention and treatment.

PMID- 12795062
TI  - Can institutional policy education really change behavior?

PMID- 12795063
TI  - The American Society of Health System Pharmacists.

PMID- 12795064
TI  - Children's competence to participate in healthcare decisions.
AB  - Advances in chronic and genetic disease management and technology create new
      challenges for healthcare professionals and patients in making informed
      decisions. The growing interest in children's involvement in their own healthcare
      decisions and a rebalancing of child and adolescent rights and responsibilities
      compounds these challenges. This article presents an overview of research and
      standards of practice regarding children's participation in research and
      healthcare decisions. Further research on children's competence to participate in
      healthcare decisions is recommended. Reasons for and against children's increased
      involvement in healthcare decisions are included. There is a preponderance of
      support for involving children in the process, and a dearth of well-articulated
      reasons to exclude them.

PMID- 12795065
TI  - Returning to competence after discipline.
AB  - Nursing regulatory boards have long taken disciplinary action against licensees
      who have violated Nursing Practice Acts. License suspensions are a common penalty
      for such violations, but rehabilitation and regaining competence also must be
      considered. The North Carolina Board of Nursing has developed and implemented two
      courses, Legal-Ethical Decision Making, and Pharmacology, which may be required
      of licensees as part of the disciplinary process. Developed by board staff, the
      courses are taught by independently contracted nurse instructors located
      throughout the state. During the courses, the licensees must acknowledge their
      specific violation and explore the reasons for occurrence and strategies for
      prevention. Upon completion of the course, instructors submit required course
      materials that are used for consideration of relicensure decisions. This article
      describes the development and implementation of the instruction program, as well
      as descriptive data on the licensees.

PMID- 12795066
TI  - [Development of new drugs is too expensive].

PMID- 12795067
TI  - [New drugs are tested on virtual patients. It will be possible to test new drugs
      on virtual patients, existing only in a computer].

PMID- 12795068
TI  - [Overuse of vitamin B12 preparations].

PMID- 12795069
TI  - [SARS. Severe acute respiratory syndrome].
AB  - Since November 2002 an epidemic of a new severe respiratory infection has taken
      place primarily in South-East Asia. Severe Acute Respiratory Syndrome (SARS) is
      assumed caused by a recently identified corona virus, which seems to be a new
      pathogen in the human population. The infection is assumed transferred primarily
      with droplets and is highly contagious within healthcare settings and families.
      Respiratory and barrier precautions are necessary to contain the virus, as it is
      contact tracing.

PMID- 12795070
TI  - [Diagnosis of vitamin B12 deficiency--time for reflection].
AB  - Since plasma methylmalonic acid (MMA) was introduced in Denmark in 1992 both MMA
      and P-cobalamins have been increasingly employed to diagnose vitamin B-12
      deficiency, and the consumption of vitamin B-12 has been almost doubled during
      the same period. The controversy about diagnosing vitamin B-12 deficiency is
      reflected in a huge geographical variation both in requisition of MMA and P
      cobalamins and in the vitamin B-12 consumption. On the basis of studies performed
      so far we conclude that MMA is a reliable method with a good nosographic
      sensitivity. However, the nosographic specificity is sparsely examined, and the
      evidence to use MMA as a primary test for diagnosing vitamin B-12 deficiency is
      still insufficient. We recommend P-cobalamins as the first line test, and if P
      cobalamins are in the grey area 125-250 pmol/l we recommend supplementation with
      MMA. For patients who also have an MMA in the grey area (0.29-0.75 mumol/l) we
      recommend that the patient is re-examined after about a year.

PMID- 12795071
TI  - [Vitamin B12 in the Nordic countries. Deficiency, diagnosis, treatment in
      Sweden].

PMID- 12795073
TI  - [Tibial traction].

PMID- 12795072
TI  - [Fibroadenoma of the breast--modern strategy of treatment].
AB  - Fibroadenoma is the third most frequent palpable phenomenon in the breast in
      women and is most often seen around the age of 30. The size varies but is in
      average between one and three centimeters. Fibroadenomas originate from a breast
      lobule and can be situated anywhere in the breast. The ethiology is uncertain but
      it seems as if hormonal factors play a role. Investigations have shown that many
      of the fibroadenomas decrease in size and even more regress. The traditional
      treatment of fibroadenomas is excision but a conservative treatment seems to be
      reasonable. We conclude that fibroadenomas in adolescents can safely be treated
      conservatively after having been examined by an experienced breast surgeon. In
      adult women a benign triple test is a prerequisite for conservative treatment.

PMID- 12795074
TI  - [Blood cultures--indication and antibiotic therapy].
AB  - INTRODUCTION: The purpose of this study was 1) to record the indication for
      obtaining blood cultures by registration of rectal temperature and presumed focus
      or symptoms 2) to register the choice of antibiotic therapy immediately after
      obtaining the blood culture and to relate it to the indication and 3) to evaluate
      the indication and choice of antibiotic therapy on the basis of the blood culture
      result. MATERIAL AND METHODS: The study is a retrospective study of all blood
      cultures obtained at a department of internal medicine. In all 432 defined
      episodes, where blood cultures were obtained, the rectal temperature and the
      presumed focus or symptoms were registered. RESULTS: In 46.1% of the episodes the
      rectal temperature was below 38.5 degrees C. The most frequently presumed focus
      was the respiratory tract, accounting for 38.2%. Significant microorganisms were
      found in 50 episodes (11.6%) and in 14 (28%) of these the rectal temperature was
      below 38.5 degrees C. In 18 episodes (36%), the antibiotics used were
      inappropriate. DISCUSSION: It is difficult to define clearly the indication for
      obtaining blood cultures. There are many parameters to be considered, the rectal
      temperature being one of the most important, though not necessarily the decisive
      guideline. In many cases the presumed focus at the time of blood culture does not
      correspond well with the microorganism isolated later. It is therefore imperative
      to collect other relevant specimens in addition to blood and to make sure that
      the antibiotic therapy covers the most frequent types of infections and most
      serious aetiologies.

PMID- 12795075
TI  - [Children with ear disorders who are treated by reflexologists or general
      practitioners].
AB  - INTRODUCTION: The aim of the study was to describe similarities and differences
      in health, quality of life, and diagnosed morbidity in 0-6 year-old children
      whose parents contact either a reflexologist or a general practitioner (GP) due
      to their child's ear disorder. MATERIAL AND METHODS: A total of 98 children who
      received reflexology treatment and 57 children who received treatment by a GP
      were included. Reflexologists and GPs described the child's symptoms, the parents
      completed a questionnaire about health status and ear disorders and a specialist
      examined and diagnosed the child. RESULTS: The most prevalent symptoms were colds
      and troubled sleep and the least prevalent were inflammation of the throat and
      poor spoken language. Parents in the reflexology group considered their children
      to be more ill than parents in the GP group (measured by number of ear disorders,
      number of antibiotic treatments, number of sickness days during the past year and
      the duration of the acute ear disorder). Furthermore, parents in the reflexology
      group reported that their children had more physical discomfort, more activity
      limitations and more emotional problems than children treated by GPs and the
      parents themselves were also more troubled by the ear disorder. The specialist
      examination showed no differences between the two groups of children, neither
      according to tympanometry nor according to diagnosis. DISCUSSION: According to a
      medical evaluation there was no difference in morbidity between children treated
      by a reflexologist and a GP. According to the parents' evaluation, children in
      reflexology treatment were more ill and their health-related quality of life was
      more affected by the ear disorder than that of children treated by a GP.

PMID- 12795076
TI  - [A case of primary peritoneal carcinoma].
AB  - A case of a 62-year-old woman with perforation of the colon caused by primary
      peritoneal cancer is described. The diagnosis and its relation with c. ovarii is
      discussed.

PMID- 12795077
TI  - [Pure red cell aplasia developed during treatment with erythropoietin. Complete
      remission during immunosuppressive therapy].
AB  - In a patient with chronic renal failure due to diabetes mellitus pure red-cell
      aplasia developed during treatment with erythropoietin (epoetin alfa). The
      treatment with erythropoietin was stopped and immunosuppressive therapy resulted
      in normalisation of the bone marrow function and increase of the Hb level to
      normal values. Pure red cell aplasia which develops during treatment with
      erythropoietin has recently been reported in a few other patients with anaemia
      due to chronic renal failure. Hitherto our patient is the first case reported in
      Denmark.

PMID- 12795078
TI  - [Two imported cases of West Nile fever in Denmark].
AB  - In the light of the current American epidemic, and since West Nile fever (WNF)
      has never previously been reported in Denmark, we describe two cases imported
      from Israel and Canada, respectively. WNF was diagnosed in a 46-year-old Danish
      tourist returning from Israel and a visiting 73-year-old Canadian citizen with
      Danish ancestry. The former manifested itself clinically as a mild flu-like
      illness, the latter as serious infection of the central nervous system. Thus, in
      addition to representing a rare case of West Nile encephalitis, it also
      constitutes one of the first reported cases of human infection of Canadian
      origin.

PMID- 12795079
TI  - [Something to learn from the Iraq war, colleagues].

PMID- 12795080
TI  - [Will cardiologists' education be approved in Europe?].

PMID- 12795081
TI  - Contagion and blame in early modern England: the case of the French pox.

PMID- 12795083
TI  - Infectious wit: metaphor, atheism, and the plague in eighteenth-century London.

PMID- 12795082
TI  - Defoe's journal and the English plague writing tradition.

PMID- 12795084
TI  - Narrating the unexceptional: the art of medical inquiry in Victorian England and
      the present.

PMID- 12795085
TI  - Microbiography and resistance in the human culture medium.

PMID- 12795086
TI  - [Development of marine-derived anti-cancer compounds].
AB  - The marine environment offers a rich source of natural products with potential
      therapeutic application. Marine organisms have evolved the enzymatic capability
      to produce potent chemical entities that make them promising sources of
      innovative cytotoxic compounds. Prominent in the identification and development
      of novel anti-cancer agents from marine sources is the Spanish biotechnology
      company, Pharma Mar, which currently has a large number of oncology products in
      late preclinical and clinical development. These include: Ecteinascidin-743 (ET
      743), Aplidin, Kahalalide F and ES-285. Many of these innovative compounds have
      novel mechanisms of anti-tumor action that have yet to be fully elucidated.

PMID- 12795087
TI  - [Malignant pleural mesothelioma].
AB  - Malignant pleural mesothelioma (MPM) used to be a rare disease, but is recently
      increasing in incidence. Most MPMs were thought to have a causal relationship
      with asbestos exposure. However, a DNA sequence similar to simian virus 40 has
      been detected in MPM tumor cells, which suggests a role of viral infection in its
      etiology. MPM predominantly afflicts men over 60 years old, with a male to female
      ratio of 3 to 1. MPM is a challenging disease in all aspects, including
      diagnosis, staging and treatment. Its diagnosis requires a panel of
      immunohistochemical stains. Multimodal treatment including surgery has shown
      significant benefit in highly selected patients. Most cytotoxic drugs
      administered as a single agent have been evaluated, but none have consistently
      demonstrated response rates greater than 20%. The combination of gemcitabine plus
      cisplatin has become a standard regimen, although there has been significant
      variability in response rates between studies. The novel antifolates pemetrexed
      and raltitrexed are promising agents and undergoing 3 phase III studies. One of
      these studies is the largest trial ever conducted in MPM patients, which
      randomized 456 patients into cisplatin with or without pemetrexed groups. The
      median survival time was 12.1 months in the cisplatin with pemetrexed arm and 9.3
      months in the cisplatin alone arm (p = 0.02). Another of these studies is
      currently being conducted to compare cisplatin with or without raltitrexed. The
      third study is comparing pemetrexed alone to supportive care. The results of
      these trials are expected to define the role of chemotherapy for patients with
      MPM.

PMID- 12795088
TI  - [The diagnosis and treatment of the thymic carcinoma].
AB  - Thymic carcinoma was indistinct for criteria of clinicopathological diagnosis.
      Recently it gets easier to diagnose thymic carcinoma, because of progression of
      WHO classification and immunohistochemical technique. Commonly, patients are men
      and in sixties. Common symptoms are chest pain and dyspnea. Most cases are
      advanced, over Stage III of the Masaoka's classification. Combined therapies e.g.
      operation, chemotherapy and radiation were done, but complete resection is
      difficult. Prognosis is poor, the 3- and 5-year survival is 48.7% and 40.6%.

PMID- 12795089
TI  - [Male breast cancer].
AB  - As male breast cancer remains rare entity (less than 1% of cases of breast
      cancer), most of our current knowledge of it has been extrapolated from its
      female counterpart. The prevalence of male breast cancer increases with age, and
      the presentation occurs at an average age of approximately 60 years, 10 years
      older than in females with the disease. The majority of patients present with a
      painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in
      diameter. There may be fixation to skin. Mammography and ultrasonography are
      useful to distinguish between breast cancer and gynecomastia. Pathologically,
      invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is
      rare. Modified radical mastectomy is a principal surgical approach, and adjuvant
      therapy has been advocated in men based on the beneficial results of it in women.
      Hormonal manipulations constitute an essential part of adjuvant therapy, as male
      breast cancers have a high rate of hormone-receptor positivity. Although
      orchiectomy was practiced in the past, today, tamoxifen is the standard hormone
      therapy. With respect to systemic chemotherapy, the most common regimens are CMF
      (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based
      regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy,
      or radiotherapy can be administered for palliative purposes. Several selective
      aromatase inhibitors are now available; however, there are limited data regarding
      their efficacy in men. The prognosis does not seem to be poor compared to that of
      females when age and stage are matched. Further studies are needed to
      characterize the biologic and molecular properties of male breast cancer and
      their prognostic significance, and to devise optimal treatment strategies.
      However, it is interesting to note that p53 and c-erbB-2, are expressed and
      angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients
      can carry BRCA2 mutations.

PMID- 12795090
TI  - [Diagnosis and treatment of carcinoid tumors in the gastrointestinal tract].
AB  - Histopathologically and biologically, endocrine cell tumors in the
      gastrointestinal tract are divided into two groups: 1) carcinoid, a low-grade
      malignancy, and 2) endocrine cell carcinoma (synonymous with small cell
      carcinoma), a high-grade malignancy. Atypical carcinoid, which has increased
      histological atypia and proliferative activity, shows more aggressive biological
      behavior than classical carcinoid. As a rule, endocrine cell carcinoma should be
      resected surgically with dissection of lymph nodes and adjuvant therapy if
      needed, while carcinoid should be treated by endoscopic resection or localized
      resection without lymph node dissection. Classical carcinoid of more than 2.0 cm
      in size and atypical carcinoid should be treated more carefully because of the
      increased risk of vascular permeation or distant metastasis.

PMID- 12795091
TI  - [Pseudomyxoma peritonei--diagnosis and treatment].
AB  - Pseudomyxoma peritonei is an unusual condition in which diffuse collections of
      gelatinous fluid are associated with mucinous implants on the peritoneal surfaces
      and omentum. It is now generally accepted that pseudomyxoma peritonei is due to
      neoplastic mucus-secreting cells within the peritoneal cavity. The diagnosis is
      not difficult before surgery, owing to the development of radiologic imaging
      studies. This disease is a malignancy that, even after excision of the metastatic
      areas, has a poor prognosis, since no effective therapy has yet been established
      besides debulking surgery.

PMID- 12795092
TI  - [Malignant melanoma of the alimentary tract].
AB  - We reviewed case reports of malignant melanoma in the alimentary tract and
      discussed the diagnosis and treatment. Cases of malignant melanoma in the
      alimentary tract have mostly originated from the esophagus and an anorectal
      lesion. Metastatic tumors occurred mainly in the stomach and the small intestine.
      Although resection with lymph node dissection was performed, the prognosis of
      these patients was worse than that of patients with carcinoma. Malignant melanoma
      of the alimentary tract might be more aggressive than that of the skin. A
      combined modality treatment including progressive chemotherapy and biotherapy is
      expected to improve the prognosis of these patients.

PMID- 12795093
TI  - [Current topics in the diagnosis and treatment of malignant fibrous
      histiocytoma].
AB  - Malignant fibrous histiocytoma (MFH) is a tumor about which much remains unknown.
      The cell origin, molecular mechanism of pleomophism and mechanism of pleomorphic
      change in a cell undergoing malignant change have not been elucidated. MFH-like
      histological changes are observed in many bone and cartilage sarcomas, and some
      renal cell carcinomas and malignant lymphomas. These changes occur in many
      subtypes of sarcomas such as osteogenic sarcoma, chondrosarcoma, leiomyosarcoma,
      rhabdomyosarcoma, and liposarcoma. MFH has been regarded as one tumor
      classification from its special histopathological features. In clinical
      pathological studies these tumors are divided into low-grade fibrous tumors and
      fibrous histiocytic tumors. With the establishment of molecular biological
      diagnostic methods, MFH-like histological features can be seen in changes in
      cellular differentiation of many sarcomas. Patients with MFH often have repeated
      recurrences before a diagnosis is made, and the tumor is partially resected.
      Furthermore, distance metastasis develops and the prognosis is poor. The
      sensitivity of MFH to radiotherapy and chemotherapy is insufficient, and evidence
      is lacking for adjuvant treatment. Rescue following initial treatment failure is
      extremely difficult. Local control of 70% to 90% can be achieved if a correct
      diagnosis is made, and a curative wide resection or salvage wide resection are
      done early. For treatment of bone and soft tissue sarcoma, a correct diagnosis
      and initial treatment are extremely important. MFHs are rare tumors that occur in
      every part of the body. Many cases need to be accumulated in joint clinical
      studies across fields according to organ and specialty, and effective treatment
      method developed. We need to advance the standardization of treatment for MFH,
      and eliminate wrong initial treatment through the active provision of
      information.

PMID- 12795094
TI  - [Kaposi's sarcoma].
AB  - Kaposi's sarcoma is a malignant tumor that is one of the major complications with
      AIDS. This disease is common in male homosexuals, and HHV-8 has been indicated to
      play a role in its pathogenesis. In treating the lesions that spread over the
      skin of the entire body, and visceral lesions, mainly of the lung, multidrug
      chemotherapy has been commonly used, but there are many problems such as
      myelosuppression and the treatment results are poor in HIV patients with advanced
      disease. In recent years, however, progress has been made with highly active
      antiretroviral therapy (HAART), and the prognosis in cases of HIV infection is
      improving. Moreover, HAART is now coming to be seen as a treatment option for
      Kaposi's sarcoma itself. In addition, with the use of new drugs such as liposomal
      doxorubicin, the therapeutic strategy for Kaposi's sarcoma is undergoing great
      changes.

PMID- 12795095
TI  - [Combined MTX.5-FU.CDGP for the treatment of head and neck cancer].
AB  - Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP)
      with methotrexate (MTX) and leucovorin (LV) was administered for modulation in
      patients with head and neck cancer. We treated 19 patients with MTX.5-FU.CDGP
      consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion
      of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at
      100 mg/m2. Six patients had recurrent head and neck cancer, and 13 had newly
      diagnosed disease. Eleven of the new patients were concurrently treated with
      radiation therapy. Treatment-associated toxicity was significant, including
      mucositis and myelosuppression, but acceptable. Sixteen patients were eligible
      for evaluation of response. The overall complete response rate was 75.0% (12/16).
      Patients treated with radiotherapy had a 90.0% (9/10) overall complete response
      rate.

PMID- 12795097
TI  - [Weekly paclitaxel administration in the adjuvant therapy of primary breast
      cancer].
AB  - PURPOSE: To investigate feasibility and toxicity of weekly paclitaxel
      administration in the adjuvant therapy of primary breast cancer. PATIENTS AND
      METHODS: Thirty-one patients with primary breast cancer received sustained weekly
      infusion of paclitaxel at a dose of 90 mg/body for 6 weeks followed by a 2-week
      interval. This weekly schedule was repeated twice. Leukocytes were checked
      immediately before every infusion and the dose was reduced to 80 mg/body when
      grade 1 neutropenia occurred. All patients were assessable for feasibility and
      toxicity. RESULTS: A total 349 weekly paclitaxel infusions were administrated to
      31 patients (median, 12 infusions/patient). The median delivered dose-intensity
      was 88.0 mg/body/week (range 80 to 90). Therapy was well tolerated and completed
      in 27 patients. Four patients refused to continue the therapy because of nausea,
      fatigue, dizziness and weight gain. Grade 2 neutropenia occurred in 10 patients
      (32.3%), but grade 3 neutropenia did not occur. Grade 1 peripheral neuropathy
      occurred in 3 patients (9.7%). Grade 1 nausea occurred in 3 patients (9.7%).
      CONCLUSION: Weekly paclitaxel administration is well tolerated with a favorable
      toxicity profile in patients with primary breast cancer in the adjuvant setting.
      Weekly paclitaxel therapy can be performed safely in the outpatient setting.

PMID- 12795096
TI  - [Neoadjuvant chemotherapy with nedaplatin and UFT for oral squamous cell
      carcinomas].
AB  - The purpose of this study was to evaluate the effect of preoperative combination
      chemotherapy with nedaplatin and UFT for oral squamous cell carcinomas. Eleven
      patients were enrolled in this study (four men and seven women, with a mean age
      of 66.3 years). They received oral UFT (300 or 400 mg/day, total 2,100-24,600 mg
      with an average of 10,700 mg) from the initial diagnosis to the day before
      surgery. They also received an administration of nedaplatin (80 or 100 mg/m2)
      about four weeks before the planned surgery. The locoregional response rate
      (complete response and partial response) was 36.4%, and histological examination
      of surgical specimens revealed a response rate of 40%. There was no relationship
      between total dose of UFT and either clinical or histological response. Three
      patients showed severe neutropenia under 1,000/m3 and all recovered with (two
      patients) or without (one) the use of G-CSF. No other severe side effect was
      recognized. From the results of this study it is suggested that this combination
      therapy is useful for preoperative patients with oral squamous cell carcinoma,
      and that it is possible for them to undergo the therapy on an out-patient basis.

PMID- 12795098
TI  - [Evaluation of weekly paclitaxel and doxifluridine (5'-DFUR) combination therapy
      in patients with advanced or recurrent breast cancer].
AB  - To evaluate the feasibility and efficacy of weekly paclitaxel and 5'-DFUR
      combination therapy in advanced or recurrent breast cancer, 13 patients were
      enrolled in this pilot study. 5'-DFUR was administered orally at a dose of 800
      mg/day for 14 consecutive days, and paclitaxel was administered by 1 hour
      infusion at a dose of 80 mg/m2 after short premedication on day 1 and 8. This was
      repeated every 3 weeks, until disease progression or severe side effects
      precluded further treatment. Antiemetic agents and G-CSF were also administered,
      as needed. Nine patients had not received prior therapy, and four patients had
      received prior anthracycline containing therapy, two of whom were concomitantly
      receiving docetaxel treatment. Median administration time was 14 weeks, and
      median time to progression was 16.6 weeks. The overall response rate was 46.2%
      with 7.7% complete response and 38.5% partial response, and the response rate was
      consistent regardless of metastatic sites. Two patients achieved stable disease
      for at least 6 months and the clinical benefit was 61.5%. Responses were observed
      in 25% of the patients with prior anthracycline therapy. Grade 3/4 side effects
      involved leukopenia in 15.4%, peripheral neuropathy in 7.7%, malaise in 23.1% and
      nausea in 7.7%. There were no complaints of severe diarrhea. Although one patient
      withdrew from this study because of a hypersensitive reaction, this regimen was
      generally well tolerated and QOL was high enough so that it was possible to
      continue the regimen. Weekly paclitaxel and 5'-DFUR combination therapy seems to
      be feasible and effective in patients with advanced or recurrent breast cancer.

PMID- 12795099
TI  - [Combined effects of toremifene and paclitaxel on human breast cancer cell
      lines].
AB  - Effects of toremifene (TOR) in combination with paclitaxel (TXL) on various human
      breast cancer cell lines were evaluated. TOR and TXL exhibited additive effects
      on estrogen receptor (ER)-positive cancer cell lines, MCF-7 and T-47D, and a sub
      additive effect on a tamoxifen (TAM)-resistant line, T-47D/TAM. To all three ER
      negative cancer cell lines, the combined treatment also showed additive effects
      on MDA-MB-134VI, MDA-MB-231 and MDA-MB-453. Furthermore, a synergistic effect was
      observed on a multi-drug resistant (MDR) line, Adr. This synergistic effect was
      more potent in the combination with TOR than that with TAM. The combined
      treatment increased intracellular TXL, and the accumulation by TOR was 1.5-fold
      that by TAM. Consequently, the ratio of G2M arrested cells was higher, with
      statistical significance, in the TOR combination than in the TAM combination. In
      addition, these synergistic effects in MDR cells were also observed in the
      combination of TXL with major clinical active metabolites, N-desmethyl-TOR (TOR
      1) and 4-hydroxy-TOR (TOR-2). These results suggest that the combination therapy
      of TOR and TXL might be an effective clinical treatment for breast cancer
      patients.

PMID- 12795100
TI  - [A case report of tongue squamous cell carcinoma showing a complete response to
      TS-1].
AB  - A 75-year-old female with squamous cell carcinoma in the left margin of the
      tongue (T2N0M0) was referred to our hospital. She was treated with oral
      administration TS-1 80 mg/day as preoperative chemotherapy. After commencement of
      TS-1 administration, the tumor size was reduced at 1 week and had disappeared
      clinically at 4 weeks. Oral administration of TS-1 was done in 2 courses at the
      same dose. After two courses, histological examination reveled a complete
      disappearance of the cancer cells. No adverse effects were seen during the
      treatment period. She remains under oral administration of UFT for maintenance
      chemotherapy and there is no evidence of recurrence of the tumor.

PMID- 12795101
TI  - [Effect of nedaplatin, 5-FU, and leucovorin combined with radiation therapy in
      unresectable esophageal carcinoma].
AB  - A 51-year-old male was assessed as having esophageal squamous cell carcinoma with
      trachea invasion and cervical lymph node metastasis. After one course of
      chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU) and Leucovorin (LV),
      the patient had progressive disease (PD) of the primary lesion and metastatic
      lymph nodes, and a side effect of severe nausea. One course of nedaplatin, 5-FU
      and LV combined with radiation was performed alternatively. The effect was
      evaluated as a partial response (PR) of the primary lesion and metastatic lymph
      nodes. There were no adverse side effects such as nausea or renal dysfunction
      except for pancytopenia of grade 2. Increased serum levels of vascular
      endothelial growth factor (s-VEGF) decreased after the chemoradiotherapy and
      increased again during continued radiotherapy alone. More information is needed
      as to whether changes in s-VEGF relate to the clinical effects of the treatment.

PMID- 12795102
TI  - [A case of gastric cancer with metastasis to cervical lymph nodes and pulmonary
      lymphangitis carcinomatosa responding to neoadjuvant chemotherapy with TS-1 and
      CDDP].
AB  - The patient was a 61-year-old man who had gastric cancer with metastasis to
      cervical lymph nodes and pulmonary lymphangitis carcinomatosa. He received daily
      oral administration of 120 mg of TS-1 (day 1-21) and systemic administration of
      100 mg of CDDP (day 8) as one treatment course. As the metastatic lesions had
      disappeared after chemotherapy, he underwent total gastrectomy. Histopathological
      examination of resected regional lymph nodes revealed marked fibrosis and a small
      amount of scattered cancer cells. Although much peritoneal dissemination was
      observed macroscopically, histopathological examination of these tumors revealed
      only fibrosis with no cancer cells. These findings supported the effect of this
      neoadjuvant chemotherapy. He died of recurrence of the carcinoma 203 days after
      surgery, without any sign of recurrence of metastasis to cervical lymph nodes or
      pulmonary lymphangitis carcinomatosa.

PMID- 12795103
TI  - [Sustained NC status for a long period after combined chemotherapy of TS-1 and
      CDDP for residual lesions following gastrectomy for gastric cancer].
AB  - A 71-year-old man with nausea and epigastralgia was referred to our hospital and
      was diagnosed with type 3 gastric cancer. Palliative resection was performed
      since radical surgery was impossible due to massive tumorous invasion to the
      retroperitoneum. Chemotherapy with TS-1 100 mg p.o. was started for the residual
      cancer lesions, with CDDP i.v. 50 mg added from the 3rd course. We did not find
      any remarkable side effects except for grade 1 loss of appetite. This
      chemotherapy was ended after the eighth course. The residual tumor did not
      disappear but did not grow, and a no change status was maintained for twelve
      months after the gastrectomy.

PMID- 12795104
TI  - [Remnant gastric cancer in which prolonged no change status was maintained with
      low-dose TS-1--a case report].
AB  - A no change (NC) status could be maintained in a patient with remnant gastric
      cancer for more than 500 days with low-dose TS-1. The patient was a 68-year-old
      woman who was found to have remnant gastric cancer during an endoscopic
      examination in follow-up on an outpatient basis after surgery for hepatocellular
      carcinoma in our department. Surgery was rejected as a treatment option because
      of severe liver dysfunction, and the patient was started on oral TS-1 80 mg/day.
      Both AST and ALT levels increased immediately after the start of TS-1, and TS-1
      was discontinued until these levels improved. It was resumed at 50 mg/day, and
      there were no subsequent adverse reactions. Endoscopic examination on day 69
      after the start of TS-1 showed that a partial response (PR) had not been
      achieved, but the lesion had shrunk. Endoscopy on day 454 after the start of TS-1
      showed it had been possible to maintain a similar state. This was a rare case in
      which it was possible to achieve prolonged same status with low-dose TS-1.

PMID- 12795105
TI  - [A patient with recurrent gastric cancer who developed TS-1 induced hand-foot
      syndrome].
AB  - Hand-foot syndrome (HFS) is a rare adverse reaction to oral fluoropyrimidine TS
      1, which contains the dihydropyrimidine dehydrogenase (DPD) inhibitor. We treated
      a recurrent gastric cancer patient with chronic renal failure who developed grade
      2 HFS, grade 2 conjunctivitis and grade 3 stomatitis soon after TS-1
      administration. Those symptoms improved with the administration of vitamin B6,
      topical emollient therapy, and so on. We thought that the continuous elevation of
      serum 5-FU concentration, due to the accumulation of DPD inhibitor from the renal
      dysfunction, led to the development of HFS, although the participation of 5-FU
      metabolites such as F-beta-alanine cannot be ruled out.

PMID- 12795107
TI  - [A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy
      for scirrhous type gastric cancer].
AB  - A 67-year-old female was admitted to our hospital in May, 2001 for examination.
      She was diagnosed with advanced gastric cancer that was inoperable due to
      peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy,
      and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and
      prolonged NC were obtained after these chemotherapies. However, pleural effusion
      and ascites appeared again, and we diagnosed progressive disease. As a third line
      chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment
      consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week,
      with a 1-week break between the courses. Two weeks after the start of this
      therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is
      considered to be promising for advanced gastric cancers, as second or third line
      chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to
      be effective in improving QOL.

PMID- 12795106
TI  - [A case of recurrent early gastric cancer with peritonitis carcinomatosa
      successfully treated with TS-1].
AB  - A 62-year-old man with carcinomatous ascites more than 5 years after early
      gastric cancer operation was admitted to our hospital because of suspected
      pancreatic cancer, and was diagnosed with a relapse of the gastric cancer. TS-1
      was administered at a dose of 120 mg/day. At the end of 1 course a partial
      response of a decrease of tumor markers and ascites and improvement of QOL was
      achieved, and the patient was followed in the outpatient clinic. The current case
      suggests that TS-1 may have a potent therapeutic efficacy in cases of gastric
      cancer relapse with carcinomatous ascites.

PMID- 12795108
TI  - [A case of advanced gastric cancer with abdominal paraaortic lymph node swelling
      successfully resected following neoadjuvant chemotherapy of TS-1 and low-dose
      cisplatin].
AB  - A 63-year-old man who had suffered from anorexia and body weight loss was
      admitted to the hospital. Upper GI series and an endoscopic examination revealed
      type 3 cancer in the posterior wall of the cardia. Abdominal CT scan showed
      enlargement of No. 16 lymph nodes. Preoperative diagnosis was stage IV gastric
      cancer (T3 (SE) H0 P0 N3), and we considered a curative operation impossible.
      Therefore, neoadjuvant chemotherapy with TS-1 and low-dose cisplatin (CDDP) was
      planned. After 4 weeks of administration, the primary lesion was reduced in size
      and the No. 16 lymph nodes were shrunken remarkably. Therefore, a total
      gastrectomy with a splenectomy, a distal pancreatectomy, and D3 lymph node
      dissection was performed. Histological findings demonstrated the degeneration of
      cancer cells and fibrosis in the primary tumor and metastatic regional lymph
      nodes. There were no viable cancer cells in the No. 16 lymph nodes. The
      histological changes against neoadjuvant chemotherapy were judged to be Grade 1b
      for the main tumor and Grade 3 for the No. 16 lymph nodes. Neoadjuvant
      chemotherapy with TS-1 and low-dose cisplatin is so effective in a short period
      that can be adapted to advanced gastric cancer for downstaging.

PMID- 12795109
TI  - [A case of colon cancer with liver metastases and lymph node metastases
      successfully treated with surgery followed by CPT-11 and 5-FU chemotherapy].
AB  - A sixty-year-old woman underwent right hemicolectomy and D2 lymph node
      dissection. However, a solitary liver metastasis and para-aortic lymph node
      metastasis were detected three months after surgery. Chemotherapy using CPT-11
      and 5-FU (civ) was immediately performed. After one course of this regimen, the
      chemotherapeutic effect was evaluated as a partial response (PR) in the liver
      metastasis, and as a complete response (CR) in the para-aortic lymph node. There
      was a massive therapeutic effect without side effects. Two further courses of
      chemotherapy were performed after changing from 5-FU to 5'-DFUR. Both regions of
      metastasis (liver and lymph nodes) continue to exhibit CR and the patient is free
      from any symptoms almost one year after surgery. The authors believe that this
      regimen is very effective and will contribute quality of life in advanced colon
      cancer patients.

PMID- 12795110
TI  - A translation of the Multidimensional Affect and Pain Survey (MAPS) from English
      to Japanese.
AB  - This paper introduces the Japanese translation of the Multidimensional Affect and
      Pain Survey (MAPS), a 101 item questionnaire which has been demonstrated to
      possess a number of advantages over the McGill Pain Questionnaire (MPQ). We also
      review validation and other studies which used translations of MAPS into Chinese,
      Czech, Italian and Russian to study cancer related and chronic pain.

PMID- 12795111
TI  - Evaluation of restenosis in major vessels and side branches.
AB  - OBJECTIVES: The indications for concurrent intervention for stenosis of a side
      branch during the treatment for stenosis of the main vessel were investigated
      using quantitative coronary angiography. METHODS: The retrospective study
      included 451 patients treated for a stenotic main vessel incorporating a side
      branch, who underwent follow-up angiography within 6 months. Patients were
      divided into Group I with the side branch treated by coronary angioplasty, and
      Group II with the side branch left untreated. Quantitative coronary angiography
      was used to measure the minimum luminal diameter (MLD) and percentage diameter
      stenosis (%DS) of the main vessel and the side branch. RESULTS: The MLD of the
      side branch after treatment was larger in Group I (1.4 +/- 0.1 mm) than in Group
      II (0.7 +/- 0.1 mm), and the %DS of the side branch after treatment was smaller
      in Group I (34 +/- 3%) than in Group II (63 +/- 2%). These differences decreased
      at follow-up to 1.1 +/- 0.1 mm, 48 +/- 2% in Group I; 0.9 +/- 0.04 mm, 46 +/- 2%
      in Group II, respectively. The MLD and %DS of the side branch at follow-up in
      Groups I and II were affected by the presence of main vessel
      restenosis[Restenosis(+): 0.9 +/- 0.1 mm, 57 +/- 4%; restenosis(-): 1.2 +/- 0.1
      mm (p < 0.05), 43 +/- 3% (p < 0.05) in Group I; Restenosis(+): 0.9 +/- 0.1 mm, 51
      +/- 8%; restenosis(-): 1.0 +/- 0.1 mm, 44 +/- 3% in Group II]. Multivariate
      analysis showed that %DS of the main vessel at follow-up was the only powerful
      predictor of restenosis of the side branch (p = 0.0249, odds ratio = 1.031,
      confidence interval = 1.004-1.059) in Groups I and II. CONCLUSIONS: Restenosis of
      the main vessel rather than the initial outcome of the side branch is the major
      influence on restenosis of the side branch.

PMID- 12795112
TI  - [Assessment of coronary artery by four-detector multislice computed tomography:
      diagnostic accuracy and limitations for coronary artery lesions].
AB  - OBJECTIVES: The applicability of four-detector multislice computed tomography
      (MSCT) was investigated for evaluating coronary arteries. METHODS: MSCT (Somatom
      Volume Zoom, Siemens) was used to evaluate the coronary arteries in 94 patients.
      The reconstructed images were analyzed using retrospective electrocardiographic
      gating to determine the image quality of the coronary arteries. In addition, the
      ability of MSCT to detect coronary artery lesions of > or = 70% (> or = 50% in
      the left main trunk) diameter stenoses documented by standard coronary
      angiography was assessed in 67 patients who underwent coronary angiography within
      the same period. RESULTS: Good image quality was displayed in 488 (58%) and fair
      in 184 (22%) of a total of 846 coronary segments, but non-assessable in 174 (21%)
      due to degraded image quality. MDCT detected 33 stenotic lesions correctly in 494
      assessable segments, comparable to coronary angiography. The sensitivity and
      specificity of MSCT were 0.79 and 0.95, respectively. However, an additional 15
      lesions were detected by coronary angiography among the non-assessable segments.
      In total, 24 lesions were missed by MSCT. Accordingly, coronary segments were
      completely assessable and correctly detected by MSCT in only 20 patients (30%),
      or 35 (52%) if the distal coronary segments were excluded from analysis.
      CONCLUSIONS: Four-detector MSCT for detection of coronary artery lesions was
      applicable to assessable segments. However, clinical use may presently be limited
      because of the insufficient overall accuracy. Further technical improvement is
      expected in the near future.

PMID- 12795113
TI  - [Spectral analysis of systolic blood pressure in atrial fibrillation].
AB  - OBJECTIVES: Power spectral analysis was used to analyze fluctuations of systolic
      blood pressure and heart rate. METHODS: Non-invasive finger plethysmography and
      electrocardiography were performed in 20 patients with chronic atrial
      fibrillation and in 10 age-matched healthy subjects with normal sinus rhythm. The
      impulse train was stored on a personal computer and the power spectrum of R-R
      interval and systolic blood pressure were obtained by Fourier analysis (0.01-0.03
      Hz). The power spectrum (log power vs log frequency) characteristically revealed
      a linear regression as 1/f beta. RESULTS: The R-R interval spectrum during atrial
      fibrillation showed a white noise-like flat spectrum when plotted as log power
      against log frequency, whereas the systolic blood pressure spectrum during atrial
      fibrillation showed a 1/f noise-like negative slope linear pattern. The spectrum
      exponent of systolic blood pressure in patients with atrial fibrillation was
      significantly lower than that in subjects with normal sinus rhythm (2.3 +/- 0.1
      vs 1.3 +/- 0.1, p < 0.0001). CONCLUSIONS: Systolic blood pressure fluctuation in
      patients with atrial fibrillation has a fractal component and is more complex
      than that of healthy subjects with normal sinus rhythm.

PMID- 12795114
TI  - [Biventricular pacing dramatically improved critical heart failure in idiopathic
      dilated cardiomyopathy: two case reports].
AB  - Two cases of dilated cardiomyopathy with intraventricular conduction delay, or
      left bundle-branch block and refractory heart failure, were markedly improved by
      biventricular pacing. The first patient's condition (Case 1) could not be
      improved despite administration of intravenous inotropic agents. He required
      mechanical ventilation and continuous hemodialysis as his condition worsened.
      Biventricular pacing was performed which was soon followed by increased blood
      pressure and decreased mitral regurgitation. As a result, mechanical ventilation,
      continuous hemodialysis and intravenous medication could be withdrawn. The second
      patient's condition (Case 2) deteriorated because of bradycardia due to advanced
      atrioventricular block. Unexpectedly, temporary right atrium-right ventricle
      sequential pacing increased mitral regurgitation and then caused heart failure,
      requiring a higher dose of inotropic and diuretic agents. Therefore,
      biventricular pacing was performed which rapidly improved both his symptoms and
      hemodynamic state, allowing reduction of the medication dose. Biventricular
      pacing dramatically improves critical conditions in patients in life-threatening
      states.

PMID- 12795116
TI  - [Cardiovascular imaging in-a month. A case of abnormal cardiac border
      accidentally detected on chest roentgenogram. Pericardial cyst].

PMID- 12795115
TI  - [Fulminant myocarditis successfully treated with a left ventricular assist
      device: a case report].
AB  - A previously healthy 28-year-old woman was admitted under a diagnosis of acute
      myocarditis. Six hours after admission, circulatory support using intraaortic
      balloon pumping and percutaneous cardiopulmonary support were introduced, because
      uncontrollable ventricular arrhythmia appeared unexpectedly. Subsequently,
      decreased peripheral platelet count appeared, in spite of improved hemodynamics.
      Therefore, a left ventricular assist device was implanted and she was weaned from
      the percutaneous cardiopulmonary support. On the fifth postoperative day, she was
      successfully weaned from the left ventricular assist device with full recovery of
      myocardial function. Myocardial biopsy demonstrated the appearance of acute viral
      myocarditis. This case suggests that the left ventricular assist device might
      offer effective circulatory support for acute fulminant myocarditis.

PMID- 12795117
TI  - [Cardiovascular imaging in-a-month. A 65-year-old man complaining of shortness of
      breath after open heart surgery. Chronic expanding pericardial hematoma after
      open heart surgery].

PMID- 12795118
TI  - [An assessment of psychological stress in patients with facial palsy].
AB  - OBJECTIVES: Facial palsy may cause excessive stress due to the obviousness of its
      manifestations. We evaluated psychological stress in patients with facial palsy.
      SUBJECTS AND METHODS: Subjects were 57 patients with Bell's palsy, 12 with Ramsay
      Hunt syndrome, and 11 with zoster sine herpete. Eighteen of 50 questions from the
      Psychological Stress Response Scale (PSRS) were selected and used to in a
      questionnaire completed by each patient on 2 separate occasions the first
      hospital visit and after recovery from facial palsy. They also completed a second
      bodily condition questionnaire before and after treatment. RESULTS: The
      psychological stress response score of patients with facial palsy was high on the
      first visit. Intermediate and high psychological stress were observed in 35% on
      the first visit. These psychological stress response score decreased after
      recovery from facial palsy. The psychological stress response of patients under
      65 years of age in those over 65 years. No gender difference was seen in
      psychological stress response. Those with herpes zoster showed a higher
      psychological stress response than others and this decreased after recovery from
      facial palsy. CONCLUSIONS: Psychological stress response score of patients with
      facial palsy was high on the first hospital visit, suggesting that we must treat
      the psychological aspects of this manifestation by adequately explaining
      prognosis and pathology, in addition to physical therapy.

PMID- 12795119
TI  - [A clinical study of ultrasonography for lymph node metastases in head and neck
      cancer].
AB  - Ultrasonography (US) is very useful in evaluating cervical lymph node swelling in
      head and neck cancers. We studied problems with US in evaluating lymph nodes.
      Cervical lymph nodes were removed by radical neck dissection or modified radical
      neck dissection from 79 patients with squamous cell carcinoma in the head and
      neck. We studied the correlation between preoperative US findings and the
      histopathological features. Preoperative lymph nodes were measured three
      dimensionally. We diagnosed lymph nodes as metastases when they meet two
      criteria: One is the shortest diameter exceeding 7 mm in level I and II and 6 mm
      in level III, IV and V. The other is shortest to longest diameter ratio exceeding
      0.5. A total of 2004 lymph nodes were removed by neck dissection, and 199 lymph
      nodes were diagnosed histopathologically as metastases. Of the 199 metastatic
      lymph nodes, 93 (46%) were diagnosed as metastases by preoperative US findings
      and 33 (17%) were false negative. Thirty-six cases were diagnosed preoperatively
      as N0 by US findings, but 15 of these were pN(+) histopathologically. In the 15
      cases, 21 lymph nodes were metastases. Of the 21 metastatic lymph nodes, 10 nodes
      were not detected by US. Thirty-one cases were diagnosed preoperatively as N1 by
      US findings, but 20 of these were pN2b histopathologically. In the 20 cases, 66
      lymph nodes were metastases. Of the 66 metastatic lymph nodes, 46 were not
      diagnosed as metastases. They often located distant level from the lymph node
      diagnosed correctly as a metastasis. US is very useful in evaluating cervical
      lymph node metastasis, but it has the limitations indicated above. If 1
      metastatic lymph node is detected by US, there will be multiple metastatic lymph
      nodes and sometimes they are distant from the original level. Radical neck
      dissection should be done for positive lymph nodes detected by US findings. If a
      lymph node is not clearly a metastasis, fine-needle aspiration cytology (FNA)
      should be done, because it provides more accurate diagnosis for metastatic lymph
      nodes.

PMID- 12795120
TI  - [A device for tracheostomized children in home care].
AB  - Tracheomized children with deglutition disturbance require frequent suction--a
      procedure that may present problems for parents and other home-caregivers. We
      introduced a suction pump to drain the thoracic cavity continuously. This reduced
      the number of times of suction was required and raised no problems.

PMID- 12795121
TI  - [Report of 2 cases of tuberculous retoropharygeal abscess in adults].
AB  - We report 2 cases of tuberculous retoropharyngeal abscess. Case 1 was a 21-year
      old man with tuberculous cervical spondylitis and pulmonary tuberculosis and Case
      2 was a 32-year-old woman with tuberculous lymph adenitis and military
      tuberculosis. Both reported sore throat and dysphagea. In case 1, throat
      examination showed a bulging abscess at the posterior wall of the pharynx. X-ray
      examination of the neck showed a massive soft tissue swelling on the lateral
      view. As soon as the diagnosis was established, prompt focal aspiration was done
      since the increasing danger of grave respiratory distress was expected. And
      moreover, surgical incision and drainage of retropharyngeal abscess were
      indicated. In case 2, intraoral midline incision through the posterior wall of
      the pharynx was administered because the abscess was small and limited. Though
      various tuberculous statics and antibiotics are available, tuberculous
      retropharyngeal abscess still occurs and should be considered to ensure rapid
      adequate attention to diagnosis and treatment.

PMID- 12795122
TI  - [A case of neurinoma of the nasal septum].
AB  - Neurinoma grows in the modulated nerve with Schwann cells, and is observed for
      all positions of the body. It is comparatively rare for neurinoma to grow in the
      nasal cavity and paranasal sinuses, however. We report a case of neurinoma of the
      nasal septum. A 24-year-old man seen for nasal obstruction was found in anterior
      rhinoscopy to have a tumor of the bilateral nasal cavity. Computed tomography
      (CT) showed a soft tissue density mass in the anterior part of the nasal cavity.
      Because we suspected neurinoma from biopsy, we resected the tumor by Denker's
      operation under general anesthesia. We found that it originated from the nasal
      septum. Histopathological findings of the tumor indicated an Antoni A type
      neurinoma. After surgery, cartilago costalis was transplanted the plastic surgery
      to correct the defect in the nasal septum. The post operative course was good and
      no signs of recurrence were seen. This is the 19th case found in the literature.

PMID- 12795123
TI  - [Bone-anchored hearing aid (BAHA): report of 2 cases].
AB  - In this first case report in Japan, we described 2 patients treated using a bone
      conductive hearing aid with skin-penetrating implant, or bone-anchored hearing
      aid (BAHA). Both suffered from chronic otitis media and had received bilateral
      canal down tympanomastoidectomy. Case 1 was a 61-year-old woman with a
      conventional air conductive hearing aid in her right ear. There was no aural
      discharge in either ear. A pure-tone average showed 82.5 dBHL (air), 44.3 dBHL
      (bone) in the right ear and 93.8 dBHL (air), 48.8 dBHL (bone) in the left ear.
      Case 2 was a 38-year-old woman with a conventional hearing aid in her left ear,
      from which there was persistent aural discharge. A pure-tone average showed 48.8
      dBHL(air), 15.0 dBHL (bone) in the right ear, and 60.0 dBHL(air), 20.0 dBHL(bone)
      in the left ear. Both underwent BAHA implant in the right ear without adverse
      reaction during 9 months of postoperative follow-up after surgery. No difference
      was seen in the aided hearing level or speech discrimination score between BAHA
      and air conduction hearing aids but both patients preferred to BAHA because of
      its greater comfort and audibility.

PMID- 12795124
TI  - [Experimental study of contraction loss effects of mouth mucosa by ethanol
      injection].
AB  - We began treating patients with simple snoring and obstructive sleep apnea
      syndrome (OSAS) with the coblator radiofrequency generator in our outpatient
      clinic from April 2001. Good clinical results have been obtained, but we noticed
      a contractile effect on mucosa from ethanol, which possesses marked sclerotic
      degenerative action on tissue as well as radiofrequency energy. We conducted a
      series of experiments in a guinea pig model to investigate the efficacy of local
      ethanol injection in contracting mouth mucosa. To examine the influence on
      respiration of liquid injection, physiological saline was gradually injected in
      decrements into the arch of the palate mucosa. We found that the safe dosage that
      did not bring about edema and subsequent dyspnea was under 10 microliters. Based
      on this finding, ethanol in concentrations of 50%, 70%, and 100% at volumes of 1,
      2, 4, 8, and 10 microliters was injected into the arch of the palate mucosa in
      guinea pigs and changes in local field mucosa were observed daily. In the 50%
      ethanol injection, no clear contractile effect on mucosa could be observed at any
      dosage. In contrast, the 100% ethanol injection led to strong tissue impairment
      that caused extensive necrotic collapse of the local field mucosa, even when the
      dosage was down to the minimum of 1 microliter. We found that, injection of 70%
      ethanol at 1 or 2 microliters, however, resulted in formation of a local field
      mucosa wound of lesser degree that healed completely within a few days,
      associated with moderate contraction of mucosal tissue. We concluded that in
      moderate dosage, 70% ethanol seems to have the potential for the treatment of
      endermosis, such as uvuloptosia (elongated uvula) and hypertrophy of palate
      mucosa, as a useful mucosa contractile agent.

PMID- 12795125
TI  - [Etiology of acute pharyngitis in adults: the presence of viruses and bacteria].
AB  - Pharyngeal swabs from patients with acute pharyngitis were evaluated for viruses
      and bacterial organisms from December 2000 through June 2001. Viral genomes were
      detected by PCR. Of 56 patients, potentially pathogenic bacteria were isolated in
      34 (60.7%), viruses in 19 (33.9%), and no etiological pathogens in 16 patients
      (28.6%). Both viral and bacterial infections were found in 13 (23.2%). Of 56
      patients, beta streptococci were found in 10 (6 with group A streptococci, 4 with
      other groups), H. influenzae in 13, S. pneumoniae in 8, and S. aureus in 7. Two
      bacterial organisms were isolated in 4 and 3 in 1. Virus infection was found in
      19 (29.7%): Adenovirus was most frequently recovered (11 cases; 57.9%), followed
      by Influenza A and B virus (4 cases; 21.0%), Parainfluenza 1 virus (4 cases;
      21.0%) and RS virus (2 cases; 10.5%). Two cases had 2 viruses infections. On the
      basis of our results, viral and bacterial coinfections are observed in early
      illness.

PMID- 12795126
TI  - [The differential effects of isoproterenol on +dp/dt max and -dp/dt max under
      volatile anesthetics in rat].
AB  - BACKGROUND: The purpose of this study is to examine the effects of isoproterenol
      on +dp/dt max and -dp/dt max under volatile anesthetics in rat. METHODS: Firstly,
      under different halothane or isoflurane (0, 0.5 MAC, 1.0 MAC, 2.0 MAC)
      concentrations, hemodynamic parameters were recorded simultaneously. Secondly,
      under different halothane or isoflurane concentrations (0, 0.5 MAC, 1.0 MAC, 2.0
      MAC), the inotropic response to isoproterenol was also studied with cumulative
      (0, 5, 50, 100, 500, 1000 pg) concentrations and hemodynamic parameters were
      simultaneously recorded. RESULTS: There were significant decreases in +dp/dt max
      and -dp/dt max in halothane and isoflurane treated rats. The decreases in +dp/dt
      max and -dp/dt max were greater in halothane treated rats than those in
      isoflurane treated rats (P < 0.05) under 2 MAC halothane. The responses of +dp/dt
      max and -dp/dt max to 500 and 1000 pg isoproterenol were significantly reduced by
      2 MAC halothane compared with the control (P < 0.05). There were no significant
      changes in +dp/dt max and -dp/dt max by administration of isoproterenol under
      isoflurane anesthesia. CONCLUSIONS: Isoflurane has less effects on +dp/dt max and
      -dp/dt max, compared with halothane. It is possible that halothane, but not
      isoflurane, has some effects on the responsiveness to isoproterenol.

PMID- 12795127
TI  - [Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig
      ventricular myocyte].
AB  - BACKGROUND: Sevoflurane causes QT interval prolongation clinically, but its
      precise mechanism has not been clarified. We examined the mechanism of QT
      interval prolongation induced by sevoflurane by means of electrophysiological
      technique in guinea-pig ventricular myocyte. METHODS: Electrocardiogram was
      recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action
      potential (AP), delayed rectified potassium current (IKr), and L-type calcium
      channel current (ICa) were monitored as whole-cell current and by voltage clamp
      techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by
      bubbling into the bathing solution. RESULTS: Sevoflurane (1, 2, 4%) increased QTc
      value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%.
      IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher
      concentration (6%) did not show further inhibition. ICa was reduced only to 87%
      of control in the presence of 2% sevoflurane and the reduction was dose-dependent
      (4, 6%). CONCLUSIONS: Sevoflurane 2% inhibited IKr, but it showed only slight
      inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase)
      and IKr (repolarization), greater inhibition of IKr than ICa could result in
      prolongation of AP. It is suggested that this mechanism may play a role in QT
      interval prolongation under sevoflurane anesthesia.

PMID- 12795128
TI  - [A retrospective study in spinal anesthesia for sumo-wrestlers].
AB  - BACKGROUND: Spinal anesthesia for the Sumo-wrestler is thought to be difficult
      because of following reasons. 1. Sumo-wrestlers are so fatty and weighty that
      piercing spinal needle into the subarachnoid space is technically difficult. 2.
      The relationship between volume of local anesthetics and attained spinal
      anesthesia level is difficult to detect. 3. Upper airway can be easily obstructed
      during sedation. METHODS: Retrospectively, we compared 30 Sumo-wrestler patients
      (group S) with normal body weight patients (group N) concerning 17 items.
      RESULTS: While all patients in group N were approached from L 3 and L 4
      interspinal space using 25 gauge spinal needles, 13 patients in group S were
      approached from another interspinal space, for example L 2 and L 3 or L 4 and L 5
      and 40% of patients in group S needed 23 gauge spinal needles. The time intervals
      from the entrance into the operating room till the end of intrathecal
      administration of local anesthetics in group S and group N were 34 and 24
      minutes, respectively (P < 0.05). The distances from the surface of the skin to
      subarachnoid space in group S and group N were 80 mm and 49 mm, respectively (P <
      0.05). CONCLUSIONS: These results indicate that subarachnoid puncture in Sumo
      wrestler patients is difficult and we should understand the specificities of
      spinal anesthesia for these patients.

PMID- 12795129
TI  - [Thoracic epidural pressure and peripheral venous pressure in the lower extremity
      during supine hypotensive syndrome].
AB  - BACKGROUND: After induction of spinal anesthesia, thoracic epidural pressure and
      left saphenous venous pressure were monitored and recorded during supine
      hypotensive syndrome in 8 pregnant patients who underwent elective cesarean
      section. METHODS: A 22 G venous catheter was inserted into the left saphena, and
      an epidural catheter for 18 G needles was positioned 5 cm cephalad in the
      epidural space through a Tuohy needle at the T 11-12 intervertebral space. Each
      catheter was connected to a pressure transducer, and recording was started in a
      supine position immediately after induction of spinal anesthesia with 0.5%
      isobaric bupivacaine at the L 3-4 intervertebral space. RESULTS: In all patients,
      epidural pressure and peripheral venous pressure synchronously increased as soon
      as they began to recover from hypotension and tachycardia regardless of uterine
      displacement to the left. CONCLUSIONS: The synchronous increase in both pressures
      was late after the hypotension probably because sympathetic block with spinal
      anesthesia inhibited vasoconstriction of the lower extremity, a factor to
      compensate for supine hypotensive syndrome. Only collateral flow via epidural
      venous plexus emptying into azygos system could not compensate for decreased
      venous return to the right atrium from obstructed inferior vena cava, and
      differences in the degree of compression of the inferior vena cava by gravid
      uterus would affect the recovery from supine hypotension.

PMID- 12795130
TI  - [Effect of continuous extradural infusion of bupivacaine on diaphragmatic
      function after upper abdominal surgery].
AB  - BACKGROUND: Diaphragmatic function is impaired after abdominal surgery. We
      investigated the effect of continuous extradural infusion of bupivacaine on
      diaphragmatic function after upper abdominal surgery using respiratory inductive
      plethysmography (RIP). METHODS: Ten healthy patients for upper abdominal surgery
      were divided into two groups; the first group of patients with continuous
      extradural infusion of morphine (group 1) and the second group of patients with
      continuous extradural infusion of morphine and bupivacaine (group 2). RESULTS: On
      the first day after surgery, there was no significant difference between the
      visual analogue scale scores in the two groups. Abdominal contribution to tidal
      volume (VAB/VT) in group 1 was significantly decreased compared to that of the
      pre-operative value. VAB/VT in group 2 was significantly higher than that in
      group 1. CONCLUSIONS: Continuous extradural infusion of bupivacaine improves
      diaphragmatic function after upper abdominal surgery.

PMID- 12795131
TI  - [Fiberoptic intubation via laryngeal mask airway under general anesthesia in the
      patients with halo vest].
AB  - Since 1991, we gave anesthesia to 155 patients with halo vest. All of 128 whose
      airways could be kept patent by laryngeal mask airway (LMA) were successfully
      intubated fiberoptically via LMA using the tube exchange catheter under general
      anesthesia. Four patients developed airway obstruction during the induction of
      anesthesia, two of whom were awakened and subsequently intubated by awake
      fiberoptic intubation. In one patient LMA could keep the airway patent. In the
      other patient, cervical immobilization by halo device was released and the
      intubation was performed with a laryngoscope. For 8 patients, awake fiberoptic
      intubation was chosen from the preoperative evaluation of the positioning of head
      and neck. Fifteen patients were intubated with a laryngoscope without trying LMA
      fiberoptic intubation. No patient developed neurological injury attributed to the
      intubation. LMA fiberoptic intubation has several advantages. Patients do not
      feel discomfort under general anesthesia. Ventilation is kept continued until LMA
      is removed. Even less experienced residents can intubate easily and safely
      without assistance. However, we must carefully diagnose and select the patient
      whose airway can be kept patent under general anesthesia. The motionless pictures
      of the intubation procedures can be seen on the web site: www.hosp.go.jp/~kobe/.

PMID- 12795132
TI  - [Anesthetic management for infected abdominal aneurysm].
AB  - A 48-year-old man was scheduled for repair of mycotic abdominal aortic aneurysm.
      Extraanatomic bypass was performed due to infection of the aneurysm. General
      anesthesia combined with continuous epidural anesthesia was performed. In spite
      of severe blood loss, hemodynamic state was stable during anesthesia and
      postoperative period. He was managed in the intensive care unit without any
      complication. In this anesthetic management, it is very important to maintain
      adequate cardiac output and circulating blood volume to prevent visceral
      ischemia.

PMID- 12795133
TI  - [Two cases of TURP syndrome with severe cardiovascular depression].
AB  - We report two cases of TURP (transurethral resection of prostate) syndrome
      showing severe cardiovascular depression without any neurological disturbances.
      One patient developed hypotension (62/42 mmHg) and ST segment depression (-2.7
      mm) on ECG during TURP. Another patient developed hypotension (60/38 mmHg) and
      nodal bradycardia (34.min-1) 15 minutes after the operation. No neurological
      signs were observed, despite severe hyponatremia (113 and 117 mEq.l-1,
      respectively). It is highly likely that hypovolemia and/or electrophysiological
      inhibition of pacemaker cell due to hyponatremia caused the symptoms. We
      emphasize that sudden circulatory depression as well as neurological disorders
      should be recognized as a major symptom of TURP syndrome.

PMID- 12795134
TI  - [Successful control of rapid heart rate in a patient with atrial fibrillation by
      continuous intravenous administration of landiolol hydrochloride].
AB  - A 79-year-old man with atrial fibrillation underwent total pharyngolaryngectomy
      and free flap reconstruction for hypolaryngeal cancer under general anesthesia.
      He developed tachyarrhythmia with ST depression and inverted T wave. The
      treatment including sufficient fluid therapy, continuous administration of
      vasodilator and intravenous digoxin failed to control the abnormalities. Then
      landiolol hydrochloride, a new cardioselective ultra-short acting beta-blocker,
      was continuously administered. Despite the relatively low doses with 1 min
      loading infusion at 0.04 mg.kg-1.min-1 and continuous infusion at 0.016
      mg.kg1.min-1, rapid control of heart rate occurred in a few minutes and inverted
      T waves were normalized in fifteen minutes. There was no significant change of
      peripheral blood pressure. The present case suggests that landiolol hydrochloride
      is effective in controlling heart rate in a patient with atrial fibrillation and
      that the optimal dose should be carefully evaluated for each case.

PMID- 12795135
TI  - [Anesthetic management for electroconvulsive therapy (ECT) in a patient with
      primary aldosteronism].
AB  - A 68-year-old male with primary aldosteronism who was scheduled for
      electroconvulsive therapy (ECT). We used propofol and suxamethonium to induce
      anesthesia, and measured plasma levels of aldosterone to evaluate the influence
      of ECT during anesthesia. Although plasma levels of aldosterone increased
      gradually after ECT, there were no complications including severe hypertension or
      arrhythmia perioperatively.

PMID- 12795136
TI  - [Anesthetic management for a patient with multiple sclerosis at exacerbation
      stage under general anesthesia].
AB  - A 39-year-old woman with multiple sclerosis (MS) at exacerbation stage underwent
      dilatation and curettage. MS is characterized by chronic inflammation,
      demyelination, and gliosis in the central nervous system. Surgical stress often
      induces exacerbation of MS symptoms. Therefore, deep anesthesia is required for
      anesthetic management in cases of MS. We monitored electroencephalograph (EEG),
      spectral edge frequency 90 (SEF 90), spectral median frequency (SMF) and delta
      amplitude for depth of anesthesia using pEEG (Drager, Germany). In this case,
      anesthesia was induced with sevoflurane and gradually increased to 5% in oxygen 4
      l.min-1 and maintained with sevoflurane 2-3% in 2 nitrous oxide l.min-1 and 2
      l.min-1 oxygen. Surgery was completed and no spike wave was observed by pEEG
      monitoring during surgery. In conclusion, sevoflurane anesthesia was useful for a
      patient with MS during exacerbation stage.

PMID- 12795137
TI  - [Anesthetic management for laparoscopic surgery in a patient with Charcot-Marie
      Tooth disease].
AB  - A 50-year-old woman was scheduled for laparoscopic cholecystectomy under general
      anesthesia. She was suffering from Charcot-Marie-Tooth (CMT) disease for 21
      years, and implanted with a permanent pacemaker for IIIrd degree AV block.
      Anesthesia was induced with fentanyl and propofol, and maintained with oxygen-air
      sevoflurane. Neuromuscular blockade was not used because of the presence of
      peripheral neuropathy and respiratory muscle weakness. We suggest that
      sevoflurane anesthesia might be useful for anesthetic management of CMT patient
      with a risk of postoperative respiratory failure.

PMID- 12795138
TI  - [Sudden increase in bispectral index during propofol anesthesia in three
      patients].
AB  - We report 3 patients who developed a sudden unpredicted increase in bispectral
      index (BIS) value during propofol and fentanyl anesthesia. The patients were
      induced with propofol 2-mg.kg-1 and fentanyl 2-micrograms.kg-1 and muscle
      relaxation was obtained by vecuronium 0.12-mg.kg-1. During induction of
      anesthesia, BIS value went down to below 50 in all three cases, and anesthesia
      was maintained by continuous infusion of propofol at a rate of 5 mg.kg-1.hr-1 and
      intermittent administration of fentanyl. Forty to sixty min after starting the
      operation, BIS value increased suddenly (up to 80) and the body movement of the
      patients was observed. The serum concentration of propofol was approximately 2.5
      micrograms.ml-1. All patients were successfully treated with increasing the
      infusion rate of propofol and additional administration of fentanyl. No clear
      recall or explicit memory during operation was observed after anesthesia, but,
      anesthesiologists might have to pay more attention to unpredictable changes of
      anesthetic depth during propofol anesthesia using target controlled infusion.

PMID- 12795139
TI  - [A case of Guillain-Barre Syndrome complicated with Fat Embolism syndrome].
AB  - A 22-year-old man was admitted to our ICU for treatment of fat embolism syndrome
      complicated with multiple bone fractures. Acute respiratory distress syndrome
      developed, and the patient received steroid therapy. During the steroid therapy,
      symmetrical proximal muscle weakness of all four limbs without sensory
      abnormalities and autonomic nervous system dysfunction developed. Cerebrospinal
      fluid showed albuminocytologic dissociation. Blood examination showed herpes
      simplex virus and cytomegalovirus infection. The patient was diagnosed as having
      Guillain-Barre syndrome, but he recovered completely one month after admission.
      It is thought that the prolonged steroid therapy for acute respiratory distress
      syndrome in this case induced viral infection that might have caused Guillain
      Barre syndrome.

PMID- 12795140
TI  - [Anesthetic management of therapeutic angiogenesis with autologous bone marrow
      cells for medically intractable angina pectoris].
AB  - We report anesthetic management of therapeutic angiogenesis with autologous
      marrow cells for medically intractable angina pectoris. A 64-year-old man
      suffering from severe angina after multiple bypass surgery was presented for this
      novel procedure. Under general anesthesia with propofol, about 650 ml of bone
      marrow was aspirated from his ilium in prone position. Hypotension was treated
      with volume infusion and the use of vasoactive drugs. Next, left thoracotomy was
      performed with the patient in right lateral position. With the aid of one lung
      ventilation, the apex and the posterior wall of the heart, where ischemia had
      been localized, was exposed. An epicardial stabilizer was used to immobilize the
      apex where purified marrow cells were manually injected. Ventricular premature
      beats occurred when marrow cells were injected, but they were self-limited. The
      procedure was completed without any serious complications. Prevention of
      perioperative myocardial ischemia, volume supplementation during bone marrow
      aspiration and preparation for ventricular arrhythmia during injection were
      suggested to be the key issues in the management of this procedure.

PMID- 12795141
TI  - [Determination of cotinine in human urine by gas chromatograph-mass
      spectrometry].
AB  - A gas chromatograph-mass spectrometric assay has been developed for the
      quantitation of cotinine, the major metabolite of nicotine, in human urine.
      Extraction or condensing procedure was not required and the method reduced time
      involved in sample preparation. The analytes were separated on the fused-silica
      capillary column. The operating conditions were: injector, 250 degrees C;
      detector, 280 degrees C; column, 50-250 degrees C. The total gas flow-rate of
      helium (carrier) was 50 ml.min-1 and the pressure of column inlet was 100-200
      kPa. The retention time was 18.1 min and the limit of quantitation was 5 ng.ml-1.
      This method provides an easy and simple assay for the detection of cotinine in
      clinical settings.

PMID- 12795142
TI  - [The temperature measurement of infusion fluid by infrared thermometer is useful
      for safety in infusion therapy].
AB  - BACKGROUND: The measurement of infusion fluid temperature is important for
      patients' thermoregulatory management. However, we usually estimate the
      temperature by touching and feeling the surface of the infusion bag. Accordingly,
      there is increasing demand for more quantitative method to measure infusion fluid
      temperature. METHODS: In the operating room we evaluated the accuracy and
      precision of the infrared thermometer (Genius) for the measurement of infusion
      fluid temperature compared with the thermistor. RESULTS: The fluid temperature
      measured by Genius is accurate with sufficient precision compared with that
      measured by thermistor. CONCLUSIONS: The temperature measurement of infusion
      fluid by infrared thermometer is clinically helpful and useful for patients'
      safety.

PMID- 12795143
TI  - [Prophylactic strategies for perioperative pulmonary embolism].
AB  - BACKGROUND: Incidence of perioperative pulmonary embolism (PE) has increased in
      Japan probably due to the modernized life style. As the mortality rate of PE is
      very high, its prophylaxis is important. Therefore, prophylactic strategies for
      PE were instituted in the entire hospital. METHODS: Elastic stockings (ES) for
      preventing perioperative deep vein thrombosis in lower extremities were worn from
      the morning of the operation until the beginning of ambulation. Intermittent
      pneumatic compression (IPC) apparatuses were used in combination with ES. IPC
      apparatus was employed right after induction of anesthesia until leaving
      postanesthetic care unit (PACU). Seventy percent of patients stayed in PACU until
      the morning after the operation and the other patients for a few hours after the
      end of surgery. RESULTS: We managed 4,200 patients with this method. We
      experienced one symptomatic deep vein thrombosis but not severe or moderately
      severe PE. However, it is difficult to evaluate the incidence of mild PE because
      it is usual that symptom such as chest discomfort is thought as an indefinite
      complaint and its cause is not investigated further. CONCLUSIONS: Our preventive
      strategies seem to be useful to decrease the incidence and severity of
      perioperative PE.

PMID- 12795144
TI  - [New study on the history of anesthesiology--(9) a brief history of "N2O Study
      Society"].
AB  - In Japan nitrous oxide has been manufactured since 1955 at the request of General
      Headquarters of the Allied Forces. Two years later in 1957, a manufacturer built
      a small society for the study and popularization of nitrous oxide anesthesia as
      well as general anesthesia. The society gave more than twenty seminars for this
      purpose in various cities in a period of 8 years from 1957 until 1965. At the
      seminars, Prof. Yamamura of Tokyo University and other professors of
      anesthesiology gave their lectures on basic science of nitrous oxide anesthesia
      and demonstrated its use for surgical patients. In July 1962, a fatal accident of
      explosion during ether anesthesia occurred in a hospital in Tokyo, in which a 25
      year-old male died due to combustion and explosion triggered by electrical
      cauterization during surgery of pulmonary empyema. This accident facilitated and
      accelerated rapid and wide spread of nitrous oxide anesthesia as well as
      anesthesiology in general in Japan.

PMID- 12795145
TI  - [Treatment of strategy for traumatic disruption of the thoracic aorta accompanied
      by multiple trauma].
AB  - Disruption of the thoracic aorta due to blunt chest trauma is often fatal and
      should generally be treated surgically as soon as possible. However, cases of
      disruption of the thoracic aorta due to blunt chest trauma are often complicated
      by damage to vital organs, making treatment difficult. Our policy is to treat
      other organs before treating the thoracic aorta in 1) cases in which fracture of
      the pelvic bone or bleeding from abdominal cavity organs is causing shock and 2)
      cases of severe cerebral contusion or intracranial hemorrhage that require
      emergency surgical treatment. The use of a stent for treatment of acute-stage
      cases should be considered prudently.

PMID- 12795146
TI  - [Adhesion or organization during surgery due to mediastinoscopy before induction
      therapy for non-small cell lung cancer].
AB  - We conducted a retrospective study to investigate amounts of adhesion or
      organization during surgery due to mediastinoscopy before induction therapy for
      non-small cell lung cancer (NSCLC). A case series of 13 patients (c-stage IIIA in
      11 and IIIB in 2) with right-side NSCLC who underwent induction therapy were
      assessed. They were between 39 and 71 years old and 8 males and 5 females.
      Induction therapy was chemotherapy alone in 4 cases and chemo-radiotherapy in 9
      cases. The mediastinocopy was used in 4 cases. Mediastinal lymph node resection
      was incomplete in 3 of the 4 (75%) cases among the mediastinoscopy group but the
      no-mediastioscopy group had no incomplete resection (p = 0.01), though 2 of the 9
      (22%) cases among the chemo-radiation group and 1 of the 4 (25%) among the chemo
      alone group (p > 0.9). Severe adhesion or organization can occur after the
      mediastinoscopy and induction therapy, which might be a course of incomplete
      mediastinal lymph node resection.

PMID- 12795147
TI  - [Familial aortic dissection; cases involving a father, mother, and son].
AB  - The occurrence of familial aortic dissection is rare in cases that are not linked
      to Marfan syndrome. We report the 3 cases of acute aortic dissection, involving
      both parents and their son. Case 1 (father case): 79-year-old male visited a
      nearby doctor complaining of severe chest and back pain. He was diagnosed as
      acute aortic dissection (Stanford type A). An emergency operation was carried out
      and he had an artificial vascular replacement of ascending aorta and arch
      portion. Case 2 (mother case): 73-year-old female was treated for hypertension.
      Suddenly, she had a terrible epigastralgia and back pain. The contrast enhanced
      chest computed tomography (CT) revealed an acute aortic dissection (Stanford type
      A). The ascending aortic aneurysm ruptured in the ambulance while she was
      transferred to our hospital. She arrived at our hospital after cardiac and
      respiratory arrest. We attempted to perform cardiac massage, but we could not
      bring her back to life. Case 3 (son case): 48-year-old male was transferred to
      our hospital diagnosed with acute aortic dissection (Stanford type A). The
      ascending aorta replacement was performed on the same day. We were able to save
      cases 1 and 3 by performing surgery. Aortic dissection is thought to be the
      disease of medial degeneration. Hereditary links to aortic dissection are not
      well understood, with the exception of Marfan syndrome cases. The investigation
      of genetic mechanisms related to aortic dissection will be expected in the
      future.

PMID- 12795149
TI  - [Assessment of left internal thoracic artery grafts by atrial pacing].
AB  - The flow reactivity of a left internal thoracic artery graft (LITAG) in response
      to atrial pacing was evaluated in 14 patients who underwent coronary artery
      bypass grafting (CABG) with LITAG to left anterior descending artery (LAD).
      Systolic peak velocity and diastolic peak velocity were recorded using a duplex
      scanner of 7.5 MHz, and flow volumes in each phase and flow ratio were
      calculated. The external temporary atrial pacing was used to increase heart rates
      25 and 50%. Diastolic peak velocity and flow volume increased predominantly on
      both pacing rates. In contrast, systolic peak velocity decreased when heart rate
      was raised 50%, and there was no significant difference between the pacing modes
      in systolic flow volumes. As a result, flow ratio increased predominantly on both
      pacing rates. Based on the present studies, there may be some advantages with
      atrial pacing to increase the LITAG flow in response to the myocardial oxygen
      demand.

PMID- 12795148
TI  - [Needle tract implantation of thymoma after transthoracic needle biopsy].
AB  - A 53-year-old man was admitted to hospital because of an anterior mediastinal
      mass. For definite diagnosis, needle biopsy was performed under ultrasonic
      examination. The histopathological diagnosis was thymoma and thymo-thymectomy was
      performed. The tumor recurred in the right anterior chest wall 10 years later. It
      is suggested that the thymoma tissue had been implanted in the needle tract. To
      our knowledge, this is the 2nd reported case of thymoma which has been implanted
      in the needle tract.

PMID- 12795150
TI  - [The use of right ventricular support with a centrifugal pump in a case with
      right ventricular failure due to intraoperative right ventricular infarction].
AB  - The patient was 67-year-old woman with mitral valve restenosis and regurgitation,
      tricuspid insufficiency, and left atrial dilatation who underwent mitral valve
      replacement, tricuspid valvuloplasty, and left atrial plication. The patient
      developed right ventricular (RV) failure due to RV infarction when she was weaned
      from cardiopulmonary bypass (CPB). Therefore, CPB was resumed to be followed by
      intra-aorta balloon pumping (IABP). However, complete response was not obtained.
      Thus, right ventricular support was performed using a centrifugal pump, and the
      patient could be weaned from CPB. Three days after surgery, the right ventricular
      support was discontinued, and IABP was removed 7 days after surgery without
      marked changes in hemodynamics. Although RV failure due to RV infarction is a
      serious intraoperative complication, favorable results were obtained by
      combination therapy with IABP and right ventricular support using a centrifugal
      pump in our patient.

PMID- 12795151
TI  - [The optimal procedure for chylothorax after operation for thoracic esophageal
      cancer; reasonable approaches to the thoracic duct from the point of view of
      routes for esophageal replacement].
AB  - In general, chylothorax after esophagectomy with lymph node dissection under
      thoracotomy is a rare postoperative complication. We report a 71-year-old man who
      developed chylothorax following esophagectomy and 3-field lymph node dissection
      together with reconstruction using stomach through the posterior mediastinum, and
      discuss ideal approaches that are less invasive and make it possible to provide
      better exposure of the thoracic duct. In selecting the ideal approach, the most
      important thing is differences in routes for esophageal replacement. The
      anatomical relation between the location of a conduit adopted for reconstruction
      of the resected esophagus and the thoracic duct should be considered in each
      case. In the case of the retrosternal or antesternal route, a video-assisted
      thoracoscopic approach allows for easy detection of the thoracic duct while
      reducing surgical invasiveness, because there is no conduit in the posterior
      mediastinum. On the other hand, a conduit interrupts the visual field of
      thoracoscopy in the case of the posterior mediastinal or intrathoracic route.
      Drawing up of a conduit to gain a good operative field involves some risks in
      protection of the vascular pedicle. Therefore, a transabdominomediastinal
      approach is an optimal option. With this approach, we could easily find the
      thoracic duct and directly ligate it just cranial to the hiatus, resulting in a
      remarkable decrease in discharge through the thoracic drainage tube. In addition,
      we present an intelligible intraoperative photograph.

PMID- 12795152
TI  - [Is it unnecessary to attach a temporary pacing wire in off-pump coronary artery
      bypass?].
AB  - In open heart surgery, the efficacy of temporary pacing to control perioperative
      cardiac dysrhythmias is well known. However, a temporary pacing wire is not
      routinely attached during minimally invasive direct coronary artery bypass
      because of its less invasiveness. In case of off-pump coronary artery bypass
      (OPCAB) with mediansternotomy, is it also unnecessary? We report 2 patients
      undergoing OPCAB without postoperative temporary pacing wire who suffered from
      possibly fatal rhythm disturbances after operation, and needed long
      hospitalization. After these experiences, we routinely attach a temporary pacing
      wire during OPCAB with mediansternotomy. We believe, in case of OPCAB, a
      temporary pacing wire is as effective as in conventional CABG.

PMID- 12795153
TI  - [Spinal cord ischemia complicated with acute aortic dissection and intramural
      hematoma; report of two cases].
AB  - Spinal cord ischemic injury is one of te most serious complications in patients
      with aortic dissection. We experienced 2 cases with severe upper back pain and
      paraplegia of the lower extremities as initial manifestations of acute DeBakey
      type IIIb aortic dissection (case 1) and aortic intramural hematoma (IMH) from
      ascending aorta to abdominal aorta (case 2). Paraplegia was permanent and spinal
      cord atrophy was proved at Th 9-10 by the magnetic resonance imaging (MRI) in
      case 1. The aortic IMH regressed rapidly and paraplegia was transient in case 2.
      The MRI obtained 18 days after the onset showed scattered small lesions within
      the spinal cord at Th 4-7.

PMID- 12795155
TI  - [Total aortic arch replacement with a right femur neck fracture on chronic renal
      dialysis; report of a successful case].
AB  - Although recent operative outcome for aortic arch aneurysm has been improved by
      various newly-devised assistant measures, satisfactory results have not been
      obtained in cases with serious preoperative complications, such as chronic renal
      failure. We present here an operative case of a 67-year-old woman on chronic
      hemodialysis with a calcified aortic arch aneurysm and a right femur neck
      fracture. First, we performed femur head replacement under careful hemodynamic
      control. After her mobilization was achieved, total aortic arch replacement was
      performed in "arch-first technique" using deep hypothermia plus retrograde
      cerebral perfusion in consideration of her calcified vessels. Her postoperative
      course was uneventful. We believe that early mobilization was a key for her
      recovery, because it was useful to prevent postoperative complications such as
      pulmonary infection and atelectasis. Our experience suggested that meticulous
      management throughout the whole perioperative course is very important for total
      aortic arch replacement in such complicated cases.

PMID- 12795154
TI  - [Preoperative autologous blood donation with cardiac surgery].
AB  - BACKGROUND: Preoperative autologous blood donation is commonly used to reduce
      exposure to homologous blood transfusions among patients undergoing elective
      cardiac surgery. The purpose of this study was to ascertain how much volume of
      predonated autologous blood need to avoid of homologous blood transfusion in
      cardiac procedure. METHODS: One hundred twenty-eight patients underwent scheduled
      cardiac procedure between January 1998 and December 1999. Group 1: 400 ml
      predonated, operation without cardiopulmonary bypass (CPB) [n = 33], group 2: 800
      ml predonated, operation without CPB (n = 23), group 3: 800 ml predonated,
      operation with CPB (n = 36), group 4: 1,200 ml predonated, operation with CPB (n
      = 36). Surgical procedures underwent only off-pump coronary artery bypass
      grafting (OPCAB) in groups 1 and 2. In groups 3 and 4 included coronary artery
      bypass grafting (CABG), valve replacement, CABG + valve replacement and atrial
      septal defect repair. RESULTS: There were no significant differences in mean body
      weight, mean preoperative hematocrit values or mean volume of intraoperative
      blood loss between groups 1 and 2. There were no significant differences in mean
      age, mean body weight, mean preoperative and postoperative day-7 hematocrit
      values, mean volume of intraoperative blood loss or mean CPB time between groups
      3 and 4. The mean postoperative day-7 hematocrit value was significantly lower in
      group 1 than in group 2. Homologous blood transfusion was avoided in 63.6% of
      those with predonation of group 1 versus 100% at group 2 (p < 0.05), 86.1% at
      group 3 versus 94.4% at group 4 (p < 0.05). In group 3, all patients who
      underwent redo operation or CABG + valve replacement needed homologous blood
      transfusion. CONCLUSIONS: Autologous blood transfusion is effective for reducing
      the homologous blood requirement. It also seems that predonation of 800 ml may be
      sufficient to avoid homologous blood transfusion in cardiac surgery, however
      predonation of 1,200 ml is desirable in cases of redo operation or CABG + valve
      replacement.

PMID- 12795156
TI  - [Surgical treatment in an infant with atrial septal defect and persistent left
      superior vena cava draining into the coronary sinus; report of a case].
AB  - A 8-month-old boy with ostium secundum atrial septal defect and persistent left
      superior vena cava draining into the coronary sinus underwent surgical treatment
      because he had required long-term ventilator support due to congestive heart
      failure and respiratory distress. The left superior vena cava and dilated
      coronary sinus produce a ridge in the left atrium, causing a subdivided left
      atrium. In this case, the early symptom could be explained by an obligatory left
      to right shunt at the level of the left atrium resulting from a ridge produced by
      the left superior vena cava and the colonary sinus, as a subdivided left atrium.

PMID- 12795157
TI  - [Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade; report of a
      case].
AB  - The ruptured aortic arch aneurysm with cardiac tamponade is rare and has severely
      high mortality. We report a case of ruptured aortic arch aneurysm with cardiac
      tamponade. A 66-year-old man who had syncope attack was transferred to city
      hospital. Brain computed tomography (CT) showed no significant lesion and he
      admitted to our hospital for suspecting of aortic dissection. Chest CT showed
      ruptured aortic arch aneurysm and pericardial effusion. Emergent operation was
      done on the same day. It was found that the hematoma beneath the tunica
      adventitia existed at the distal arch and extended to the ascending aorta.
      Cardiac tamponade was caused by rupture of subadventitial hematoma in pericardial
      space. Aortic arch replacement was performed using selective cerebral perfusion
      under deep hypothermia. Postoperatively, he had no cerebral complication and was
      discharged uneventfully.

PMID- 12795158
TI  - [Showing no increase of C-reactive protein and developing non-bacterial median
      chest wound dehiscence after coronary artery bypass grafting].
AB  - A 72-year-old male underwent coronary artery bypass grafting for 3 vessels
      disease. After the operation, the peak C-reactive protein (CRP) level was 0.85
      mg/dl and CRP levels stayed very low. Forty days after the operation the patient
      developed a progressive median chest wound dehiscence but the bacterial cultures
      were negative. In spite of conventional therapies such as debridement of necrotic
      tissue or irrigation, the wound granulation was underdeveloped. After 6 months an
      epidermis had developed to cover the wound.

PMID- 12795159
TI  - [Surgically treated mucoepidermoid carcinoma in a 6-year-old boy; report of a
      case].
AB  - A 6-year-old boy was admitted to our hospital with a history of recurrent
      obstructive pneumonia and hemoptysis. A chest computed tomography (CT) showed
      atelectasis in the left lower lobe. Angiograpy, which was performed for the
      suspicion of pulmonary sequestration, showed no feeding artery and revealed
      bleeding from the bronchial artery in the left lower lobe. As hemoptysis would
      not stop, an emergency left lower lobectomy was performed. Macroscopic
      examination of the resected specimen revealed a mass measuring 20 x 15 x 17 mm in
      the S8 proximal lung parenchyma, bronchiectasis, and an abscess in the distal
      lung parenchyma. Histopathologic examination determined the tumor was a
      mucoepidermoid carcinoma. Immunohistochemical staining revealed some tumor cells
      were positive for CA 19-9. The child has not had a recurrence 3 years
      postoperatively.

PMID- 12795160
TI  - [Thymic carcinoma (mixed small cell undifferentiated squamous cell carcinoma);
      report of a case].
AB  - A 52-year-old man was admitted to our hospital on October, 1997 with complains of
      left anterior chest pain. A chest X-ray and computed tomography on admission
      showed evidence of a mass in the left anterior mediastinum. The patient was
      treated with combination chemotherapy [cisplatin (CDDP), etoposide (VP-16)] and
      radiation therapy (2 gray x 25 days), preoperatively. Median sternotomy revealed
      a tumor invading into the left anterior chest wall, the pericardium, and partial
      pleura. The tumor was extirpated with combined resection of invaded organs.
      Microscopically and immunohistochemically, the tumor was diagnosed mixed small
      cell and undifferentiated squamous cell carcinoma documented by Snover et al. The
      patient was discharge on March 1998, but 2 years later after operation, he was
      dead by recurrent. We reported a rare case of thymic carcinoma.

PMID- 12795161
TI  - [Catamenial pneumothorax due to diaphragmatic endometriosis; report of a surgical
      case].
AB  - A 27-year-old female was complained repeated right pneumothorax. Each episode was
      obviously related to the onset of menstruation, suggesting catamenial
      pneumothorax. Thoracoscope revealed the presence of several fistulas in the
      central tendon of the diaphragm. Partial resection of the diaphragm including
      these lesions was performed under thoracoscopic procedure. Microscopic
      examination of the excised specimen showed endometriosis. The patient was
      followed without hormonal therapy, but recurrent pneumothorax occurred. For the
      catamenial pneumothorax, hormonal treatment is considered necessary even after
      surgical treatment.

PMID- 12795162
TI  - [Experience with the memotherm stent in high-risk urinary retention patients].
AB  - PURPOSE: We report on our experience with the Memotherm stent implanted in high
      risk patients who had an indwelling catheter. PATIENTS AND METHODS: Seventeen
      patients (mean age 80.6 years, range 55 to 93) who had an indwelling catheter
      were treated by placement of the Memotherm stent. The mean duration time of
      indwelling catheter were 12.7 months (range 1 to 60). The methods of implantation
      was used the special delivery system and treatment can be done with the patient
      under local anesthesia with non-steroidal anti-inflammatory drug. To assess the
      efficacy of the treatment we measured urinary peak flow rate (ml/sec), residual
      urine volume (ml) and residual urine rate (residual urine volume/total urine
      volume: %). Subjective symptoms were evaluated using the International Prostate
      Symptom Score (I-PSS). The mean follow-up time was 3.3 months (range 1 week to 8
      months). RESULTS: There were no severe medical problems associated with stent
      placement. Sixteen patients were able to void immediately after insertion of the
      stent. The remaining 1 required an indwelling catheter to 2 months, however,
      eventually able to void. Only 7 of the 17 patients can be evaluation for urinary
      flow and residual urine, nevertheless the mean urinary peak flow rate showed 9.7
      ml/sec, the mean residual urine volume was 77.4 ml, and the mean residual urine
      rate was 27.5%. Also, average I-PSS showed 13.4 in these patients. CONCLUSIONS:
      As a results of this study, the Memotherm stent is good conservative therapy for
      high-risk urinary retention patients.

PMID- 12795163
TI  - [Carcinoma of urachus: report of 15 cases and review of literature--is total
      cystectomy the treatment of choice for urachal carcinoma?].
AB  - PURPOSE: This study was undertaken to determine the most appropriate type of
      operation for the improvement of the radical cure rate and QOL of patients with
      urachal cancer. We assessed the association between the stage, type of operation,
      and prognosis of cases we experienced and those reported in Japan. PATIENTS AND
      METHOD: The subjects included 15 cases of urachal cancer we have experienced in
      the past 14 years. While clarifying the clinical patterns of these cases, the
      association between stage, type of operation, and prognosis was studied. Of the
      cases of urachal cancer reported in Japan in the recent 20 years, 75 cases in
      which the stage, type of operation, and prognosis were documented were selected,
      and the association between the stage and outcome in each type of operation was
      studied. RESULTS: In regard to stage, all the cases were rated as more than IIIA.
      As for prognosis, 9 cases (60%) are alive without cancer at the present time with
      a mean survival time of 7 years. Of the above patients, 3 underwent cystectomy
      and 6 underwent en bloc segmental resection (herein after referred to en bloc).
      Recurrence or cancer death was experienced in 5 patients, 2 of which were
      classified as stage IIIA and 3 as IIID. Of these patients, one underwent en bloc,
      3 partial resection of the bladder, and one underwent exploratory laparotomy. As
      far as our study of the cases reported in Japan is concerned, the prognosis of
      the cases having undergone only partial resection of the bladder was poor, while
      of the cases having undergone en bloc or total cystectomy 88-100% were alive
      without cancer for more than 2 years if their stage was classified as IIIA or
      below. On the other hand, prognosis was very poor whatever the type of operation
      in the cases whose cancer was stage IIIC or above. CONCLUSIONS: It appears that
      the en bloc is most appropriate as the type of operation for the cases of urachal
      cancer and that the application of total cystectomy is limited to some cases. In
      performing the en bloc, an extensive resection of the peritoneum, resection of
      the posterior sheath of the rectus muscle of the abdomen, and dissection of the
      intrapelvic lymph nodes in addition to the conventional types of operation should
      be carried out positively.

PMID- 12795164
TI  - [Prevalence and preference with regard to various surgical treatments for benign
      prostatic hypertrophy: a survey for the Japanese endourology and ESWL society
      member].
AB  - BACKGROUND AND PURPOSE: We conducted a questionnaire survey concerning the
      prevalence and preference with regard to various types of surgical treatment for
      benign prostatic hypertrophy (BPH), in order to gather preliminary data that may
      be helpful for standardizing the surgical treatment of BPH. METHOD: A
      questionnaire survey was mailed to institutes in which a council member of the
      Japanese Endourology and ESWL Society was present. The questions dealt with the
      type and volume of surgical treatment experienced previously, and the treatments
      which had been performed in each institute during 2000. Preferences concerning
      cost effectiveness, safety, degree of invasion, efficacy, overall usefulness, and
      the possibility of prevalence from now on at general hospitals were also asked
      with regard to each surgical treatment. RESULTS: Of the 155 institutes to which
      the questionnaire was sent, 70 responded (45% response rate). TUVP (transurethral
      vaporization of the prostate by thick-loop) was second to TURP (transurethral
      resection of the prostate) both regarding the volume of the surgical treatment
      that had been experienced previously, and the volume that had been performed
      during 2000. TURP was recognized as the most preferred treatment with regard to
      both cost effectiveness and overall usefulness, while TURF (transurethral
      radiofrequency thermotherapy) was preferred both for safety and reduced
      invasiveness, and open surgery for efficacy. Minimal invasive surgical treatment,
      such as TUVP, followed by ILCP (interstitial laser coagulation of the prostate)
      and TUMT (transurethral microwave thermotherapy) was recognized as the most
      preferable treatment for dealing with the prevalence from now on at general
      hospitals. CONCLUSION: Each minimal invasive surgical treatment was recognized as
      being safer and less invasive, but less effective and less useful compared to
      TURP. Among these surgical treatments, TUVP by thick-loop was recognized as being
      second choice to TURP with regard to efficacy and overall usefulness. As a matter
      of course, it would seem to be essential to evaluate long-term efficacy in
      addition to both safety and invasiveness when trying to standardize the surgical
      treatment for BPH.

PMID- 12795165
TI  - [Cost-utility analysis of androgen ablation therapy in metastatic prostate
      cancer].
AB  - BACKGROUND: As Bayoumi, et al pointed out in their article (J. Natl. Cancer Inst.
      2000, vol 92, p 1731), it is evident that treatment of prostate cancer with
      Luteinizing Hormone Releasing Hormone (LHRH) analogue costs more than treatment
      by bilateral orchiectomy. However, patients with metastatic prostate cancer are
      usually treated with LHRH analogue. Does this mean that urologist choose higher
      cost and less Quality-Adjusted Life Year (QALY) treatment? Therefore, we
      urologists should re-analyze their conclusion whether the treatment with LHRH
      analogue is really strictly dominated (high cost and low effect). MATERIAL AND
      METHOD: We performed a cost-utility analysis using the Markov model based on a
      formal meta-analysis and literature review, using the same assumptions as
      Bayoumi, et al, from the perspective of insurer. The base case was assumed to be
      a 65-year-old man with symptomatic metastatic prostate cancer. The model used
      time horizon of 10 years. Five androgen ablation therapies were evaluated as
      first-line therapy: diethylstilbestrol diphosphate (DES), orchiectomy,
      orchiectomy + nonsteroidal antiandrogen (NSAA), LHRH analogue and LHRH analogue +
      NSAA. Outcome measures were QALY, lifetime costs and incremental cost
      effectiveness ratios. RESULTS: While DES was the least expensive therapy with the
      lowest QALY, LHRH analogue monotherapy was the second most expensive therapy with
      the longest QALY. Incremental cost-effectiveness ratios relative to DES of LHRH
      (yen 4,288,295/QALY) was cheaper than that of orchiectomy when quality of life
      (QOL) weight of orchiectomy was assumed to be 0.94 relative to that of LHRH
      analogue. Contrarily, LHRH analogue + NSAA is excluded with strict dominance and
      Orchiectomy + NSAA is excluded with extended dominance. CONCLUSION: Although LHRH
      analogue costs higher than orchiectomy, LHRH analogue can offer longer QALY than
      orchiectomy. Cost/QALY of LHRH analogue relative to DES is yen 4,288,295/QALY,
      which we considered to represent a good value. Choice of therapy depends on the
      patient's preference.

PMID- 12795166
TI  - Semen cryopreservation for patients with malignant or non-malignant disease: our
      experience for 10 years.
AB  - PURPOSE: We report our experience in 10 years of sperm cryopreservation to reveal
      the present state of the cryopreservation project. MATERIALS AND METHODS: 42 germ
      cell tumor, 110 non-germ cell tumor and 2 non-malignant disease patients who
      visited our clinic for semen cryopreservation were retrospectively analyzed.
      RESULTS: Only 7 (20%) out of 35 unilateral testicular tumor patients who had
      received no chemotherapy met the WHO criteria for sperm concentration and
      motility. However, there were no patients with azoospermia. Three testicular
      tumor patients with previous chemotherapy and 4 retroperitoneal germ cell tumor
      patients had poor sperm concentrations and motilities. Twenty (52%) out of 38 non
      germ cell tumor patients without previous chemotherapy met the WHO criteria. In
      contrast, only 9 patients (13%) met the WHO criteria among 72 patients with
      previous chemotherapy. Twenty-nine patients (40%) with chemotherapy were
      azoospermia. Totally, 74 (96%) of 77 tumor patients' semen without chemotherapy
      and 34 (45%) of 75 with chemotherapy were cryopreserved. Sperm from a patient
      with testicular torsion were cryopreserved. CONCLUSION: Most cancer patients
      without previous chemotherapy, regardless of underlying disease, had abundant
      motile sperm. However, half of the patients who had received chemotherapy did not
      have suitable sperm for freezing. It is important to inform young cancer patients
      of the cryopreservation project immediately after the diagnosis is made.

PMID- 12795167
TI  - [Neuroendocrine differentiation in adenocarcinoma of the prostate with
      progression of disease during hormonal treatment: a report of two cases].
AB  - Prostatic neuroendocrine (NE) carcinoma is a rare situation and the NE
      differentiation in the prostate adenocarcinoma appears to be characterized as
      poor prognosis, rapid tumor progression and the androgen-independent state, for
      which there is currently no successful therapy. We report two cases of NE
      differentiated prostatic carcinoma, which were diagnosed adenocarcinoma initially
      and the tumors progressed universally with NE differentiation during androgen
      suppression therapy.

PMID- 12795168
TI  - [Persistent mullerian duct Syndrome in brothers].
AB  - Persistent Mullerian duct syndrome is associated with cryptorchidism and
      transverse testicular ectopia. Such gonads are at an increased risk of malignant
      transformation. Furthermore, most patients have azoospermia. Here in we report
      about two brothers with persistent Mullerian duct syndrome. The diagnosis was
      made during surgical operation for testicular cancer in younger brother. In the
      other one, persistent Mullerian duct syndrome was diagnosed during examination
      for infertility.

PMID- 12795169
TI  - [A case of locally advanced prostate cancer with low serum testosterone
      associated with intake of an androgenic medicine].
AB  - A 74-year-old man was referred to our clinic for the work-up of digitally hard
      and irregularly surfaced prostate and elevated serum prostate-specific antigen
      (PSA). His serum PSA was elevated to 41 ng/ml, but testosterone and LH level were
      decreased to 23.5 ng/dl and 0.5 mIU/ml, respectively. He had a history of taking
      an androgenic medicine containing methyl-testosterone 2 to 3 times a week for 2
      year and 6 months. Transrectal sextant prostatic biopsy revealed moderately
      differentiated adenocarcinoma (Gleason score: 3 + 4) in 6 of 6 specimens and CT
      scan of the abdomen showed an enlarged obturator lymph-node (15 mm), resulting in
      the diagnosis of stage D1 (T3aN1M0) prostate cancer. Since serum testosterone
      level seemed to recover around the normal level after discontinuation of the
      exogenous androgen, we treated him with combination androgen blockade with LHRH
      agonist and bicaltamide, although his testosterone level was very low. Indeed,
      serum PSA decreased to 0.09 ng/ml and the right obturator node was markedly
      reduced by the hormone treatment. After the neoadjuvant therapy of 6 months
      duration, radical prostatectomy and limited pelvic lymph node dissection was
      carried out. Histologically, viable cancer cells were not found in any of
      resected lymph nodes, but they remained in bilateral lobes of the prostate
      (pT2bN0). The histological effect of the neoadjuvant hormone therapy according to
      General rule for Clinical and Pathological Studies on Prostate Cancer (3rd ed.)
      was grade 2. The patient has been well with undetectable PSA and no evidence of
      clinical failure for more than 12 months, though serum testosterone level
      recovered to near normal (288 ng/dl) 8 months after the cessation of the hormone
      treatment following the operation. Combination androgen blockade or non-steroidal
      anti-androgen agent appears to be effective for the treatment of prostatic cancer
      patients who takes exogenous androgenic medicine, even with a suppressed low
      serum testosterone level.

PMID- 12795170
TI  - Epidemiological and clinical patterns of western pacific amyotrophic lateral
      sclerosis (ALS) in Guam and sporadic ALS in Rochester, Minnesota, U.S.A. and
      Hokkaido, Japan: a comparative study.
AB  - Western Pacific amyotrophic lateral sclerosis (ALS) in Guam, so-called Guam ALS,
      is a neurodegenerative disease with a high incidence among the indigenous
      population, Chamorros, in Guam. To clarify the differences in the epidemiological
      and clinical features between Guam ALS and sporadic ALS, the surveys were
      conducted in Guam for the periods from 1980 to 1989, in Rochester, MN, USA from
      1952 to 1991 and in Hokkaido, Japan from 1980 to 1989. The crude incidence rate
      of Guam ALS was 7.5/100,000/year, which was much higher than the rates of
      sporadic ALS, 2.3/100,000/year in Rochester and 0.6/100,000/year in Hokkaido,
      although it was markedly low as compared with that in the most frequent period
      between 1950-1960s. There was no remarkable change in the incidence rate either
      in Rochester or Hokkaido island during the above study periods. The average age
      of onset of Guam ALS was 56, which was more than 10 years advancement occurring
      in the past 40 years, although it was still younger than 68 and 58 in the
      sporadic ALS cases in Rochester and Hokkaido island, respectively. The average
      duration of the illness in Guam ALS was 36 months, which was almost the same as
      those in Rochester (31 months) and Hokkaido (31 months). The changing ecology and
      socioeconomic conditions in the past 40 years in Guam might have contributed to
      the drastic reduction in the environmental risk factors. However, the incidence
      remains high during the past decade, which suggests their genetic predisposition
      to Guam ALS.

PMID- 12795171
TI  - [Mechanism of nitric oxide-dependent skin vasodilation during febrilysis].

PMID- 12795172
TI  - [In vitro model for the suicide gene therapy of AFP-producing gastric cancer
      using HSVtk gene under control of AFP promoter].

PMID- 12795173
TI  - [Biomechanical comparison of the posterolateral fusion and posterior lumbar
      interbody fusion using pedicle screw fixation system for unstable lumbar spine].

PMID- 12795175
TI  - [Experimental studies on the manner of vagal nerve disturbance associating with
      radiofrequency catheter ablation].

PMID- 12795174
TI  - Differential expression of c-maf during adipocyte and muscle cell
      differentiation.

PMID- 12795176
TI  - [Analysis of initial gap and remodeling by distraction osteogenesis in canine
      mandible].

PMID- 12795177
TI  - [Two types of bone resorption lacunae: a scanning electron microscopic and
      histochemical study].

PMID- 12795178
TI  - [Malaysia viewed from the eyes of an occupational health expert on JICA short
      term dispatch program].

PMID- 12795179
TI  - [Academic urologist: privilege, obligation & reward].

PMID- 12795180
TI  - [The efficacy of switch therapy in community-acquired pneumonia in Japan].
AB  - To evaluate the efficacy of Switch therapy for community-acquired pneumonia, we
      conducted a prospective randomized controlled study in thirty-two hospitalized
      patients. These cases corresponded to Fine's risk classes II to IV. Using a table
      of random numbers, sixteen patients were assigned to a Switch therapy group, and
      the other sixteen, to a clinical pathway group. Both groups initially received
      intravenous antimicrobials. Within the Switch therapy group, when all the
      patients were afebrile for more than sixteen hours, their intravenous
      antimicrobials were switched to oral, and the patients were discharged on the
      following day. For all patients in the clinical pathway group, the critical
      pathway was defined as an eight-day planned hospitalization, with a time-task
      matrix formatted for disease treatment, laboratory testing, physical examination,
      oxygen saturation monitoring, ambulation, diet, patient education and clinical
      outcome. Switch therapy reduced the period of intravenous antimicrobial
      administration from 7.6 days to 4.0 days (p < 0.0001). The period required to
      switch to oral antimicrobials decreased from 8.3 days to 4.8 days (p < 0.0001);
      hospital stay length, from 9.8 days to 6.5 days (p = 0.0001); and medical
      resource utilization, from 330, 373 to 227,768 Japanese yen (p = 0.0002). No
      patient from either group required readmission. In conclusion, Switch therapy was
      more efficient than management with a clinical pathway for mild to moderate
      community-acquired pneumonia in hospitalized patients.

PMID- 12795181
TI  - [Relationship between sleep disordered breathing and body weight loss in patients
      with chronic obstructive pulmonary disease].
AB  - We evaluated body weight loss and growth hormone secretion in patients with sleep
      disordered breathing associated with chronic obstructive pulmonary disease. Of 11
      patients hospitalized for pulmonary rehabilitation, five (WL group) had a history
      of body weight loss within two years before their interviews, while the other 6
      patients (NWL group) had no changes in body weight. All patients underwent body
      index measurements, pulmonary function tests, blood gas analyses, assessments of
      nutritional status, and full night polysomnography for two consecutive days.
      Growth hormone levels were measured in the first 3-hour period following falling
      asleep. There were no significant inter-group differences between the results of
      pulmonary function tests, blood gas analyses, or nutritional status assessment.
      The WL group had a significantly higher percentage loss of body weight than the
      NWL group (mean +/- S.D. 11.5 +/- 4.7% in the WL group versus 2.7 +/- 1.8% in the
      NWL group, p < 0.01). The WL group had a significantly higher sleep
      apnea/hypopnea index than the NWL group (42.4 +/- 9.5/hr in the WL group versus
      7.8 +/- 2.9/hr in the NWL group, p < 0.01). The WL group showed a higher rate of
      stage I + II sleep than the NWL group (84.9 +/- 7.0% versus 64.5 +/- 8.7%), with
      lower rates of slow wave sleep (2.2 +/- 2.1% versus 15.0 +/- 8.7%) and rapid eye
      movement sleep (12.9 +/- 6.3% versus 20.6 +/- 1.0%). The WL group showed a low
      level of growth hormone secretion with no peak in the sequential curve, but had a
      higher level of insulin growth factor-1 than the NWL group (148 +/- 36 ng/ml
      versus 90 +/- 22 ng/ml, p < 0.01). These results suggest that chronic obstructive
      pulmonary disease patients undergoing weight loss are likely to have an increase
      of growth hormone secretions in the daytime, possibly induced by underlying
      psychiatric disorders such as depression. Patients with chronic obstructive
      pulmonary disease may lose weight regardless of nutritional status because of a
      disturbance of growth hormone secretion resulting of sleep-disordered breathing.

PMID- 12795182
TI  - [A case of pulmonary actinomycosis with a unique finding in the chest MR image].
AB  - A 57-year old man, who was complaining of a productive cough and right shoulder
      pain, was admitted to our hospital because of an irregularly shaped mass located
      at rt. S1 on a chest radiograph. Bronchoscopy revealed no evidence suggesting
      lung cancer or any specific infection, either pathologically or
      microbiologically. CT-guided biopsy revealed changes resembling lymphocytic or
      plasmocytic interstitial pneumonitis with thickening of the alveolar septum and
      with accumulations of mononuclear cells and plasma cells, indicating the
      proliferation of bronchus-associated lymphoid tissue (BALT system). Since no
      definitive diagnosis was considered possible, a right upper lobectomy was
      performed. Histopathologic examination of tissue from the right upper lobe
      revealed sulfur granules and branching Gram-positive filamentous bacteria, and
      the condition was pathologically diagnosed as pulmonary actinomycosis. In the
      center of the mass lesion, the patient's chest MRI showed a very small area with
      a low signal intensity in T1- and a high signal in T2-weighted images, which
      suggested an accumulation of fluid in the actinomycotic abscess. As detailed MR
      findings in this condition have not been well described in the literature, the
      MRI evidence seen in this case may be useful for the diagnosis of actinomycosis.

PMID- 12795183
TI  - [A case of aspergillus bronchitis with effective oral itraconazole].
AB  - A 62-year-old woman with diabetes mellitus and chronic hepatitis C was admitted
      to our hospital because of fever and productive cough. A thoracic CT scan
      demonstrated a cavity in the left upper lobe, thickening of the bronchial walls
      and multiple subpleural infiltrates. Fiberoptic bronchoscopy revealed aspergillus
      bronchitis. The patient was treated with 200 mg/day of oral itraconazole, but no
      effect was seen. Treatment with 300 mg/day of oral itraconazole, however,
      resulted in improvement of the symptoms and resolution of the radiographic
      abnormalities. We report a rare case of aspergillus bronchitis.

PMID- 12795184
TI  - [A case of broncho-pulmonary aspergillosis complicated by bronchial asthma
      attack].
AB  - A 55-year-old man was hospitalized for the treatment of severe asthma. However,
      his condition improved with steroid chemotherapy under artificial ventilation,
      but high fever and multiple patchy shadows of the lung that were not responsive
      to antibiotics appeared. We detected aspergillus hyphae, probably inhaled with a
      quantity of dust in the attic of his workplace, in the sputum. We diagnosed
      invasive broncho-pulmonary aspergillosis complicated with allergic broncho
      pulmonary aspergillosis. His condition improved with anti-fungal drug treatment.
      We consider that the causes of invasive broncho-pulmonary aspergillosis in this
      case were massive inhalation of aspergillus conidia, artifical ventilation and
      steroid chemotherapy.

PMID- 12795185
TI  - [An adult case of tuberculous meningitis].
AB  - A 36-year-old man was referred to our hospital with complaints of high fever and
      headache. A diagnosis of miliary tuberculosis with tuberculous meningitis was
      made. He was treated with isoniazid (400 mg/day), rifampicin (300 mg/day),
      ethambutol (750 mg/day), pyrazinamide (1.0 g/day) and prednisolone (60 mg/day).
      However, he lost consciousness because of hydrocephalus on the second day of
      hospitalization. Emergency cerebrospinal fluid drainage improved his neurological
      symptoms. After two months, he again complained of headache with nausea and
      double vision. Numerous tuberculomas were found not only in the cerebrum but also
      in the liver, the spleen and the retina. Recurrent hydrocephalus was treated with
      a V-P shunt, and combination therapy with four antituberculous agents was
      maintained for 18 months. He was discharged in a healthy condition, although a
      mild left facial palsy remained. In addition, we examined the inflammatory
      cytokine levels in both the CSF and the serum over the period of the patient's
      hospitalization. We concluded that the cytokine levels in the CSF may be
      associated with the progress and the prognosis of tuberculous meningitis.

PMID- 12795186
TI  - [A non-cardiogenic type of pulmonary edema after administration of Chinese herbal
      medicine (shosaikoto)--a case report].
AB  - A 78-year-old woman was admitted to our institution because of dyspnea on
      exertion. The history of the present illness indicated that for past two years,
      she had been taking a Chinese herbal medicine (Shosaikoto), believed to be used
      for the treatment of liver dysfunction of unknown etiology. A chest radiograph
      showed a butterfly shadow in the middle of the lower lung fields. The arterial
      blood gases showed marked hypoxemia. A tentative diagnosis of drug-induced
      pneumonia was made, and so she was given methylprednisolone pulse therapy, but no
      improvement was seen. Acute respiratory failure occurred, and artificial
      mechanical ventilation was instituted with positive end-expiratory pressure
      (PEEP). Bronchoalveolar lavage revealed a bloody fluid which suggested alveolar
      extravasation of red blood cells. She was given a second course of pulse therapy,
      and the pulmonary edema began to resolve, and so corticosteroid was tapered off.
      She was then discharged. In the outpatient clinic, a lymphocyte stimulating test
      was performed, and showed a positive reaction for Shosaikoto. The above findings
      suggested Shosaikoto-induced non-cardiogenic pulmonary edema, a rarely seen
      disorder.

PMID- 12795187
TI  - [A case of triple malignancies (gastric cancer, lung cancer and malignant pleural
      mesothelioma) after asbestos exposure].
AB  - This case study centers on a seventy-eight-year-old man with triple malignancies,
      namely, gastric cancer, lung cancer and malignant pleural mesothelioma, all of
      which developed at different times. The histological types were adenocarcinoma of
      the stomach, squamous cell carcinoma of the lung and sarcomatous malignant
      pleural mesothelioma. Gastric cancer was treated by endoscopic mucosal resection
      2 years ago. The patient presented with a chief complaint of dyspnea, and right
      pleural effusion was found on chest radiography. The right-side effusion
      disappeared spontaneously, but a small mass on the left side was diagnosed as
      lung cancer, and so left inferior lobe resection was performed. Malignant pleural
      mesothelioma appeared after one year of pleural effusion and the patient died of
      mesothelioma one year after diagnosis. At autopsy, the gastric cancer and lung
      cancer had not relapsed and malignant pleural mesothelioma had metastasized to
      the lung, liver, adrenal gland and small intestine. He was a sailor by profession
      and it was obvious that he had been exposed to asbestos, because 538 asbestos
      bodies per 5 g of wet lung tissue were detected. His advanced age was one of the
      risk factors for the multiple malignancies, and the asbestos exposure was
      considered to have compounded these hazards to cause the triple malignancies. It
      is well known that lung cancer and malignant mesothelioma are induced by asbestos
      exposure, but multiple cancers including lung cancer and malignant mesothelioma
      are extremely rare.

PMID- 12795188
TI  - [A case of pulmonary mucormycosis diagnosed through video-assisted thoracoscopic
      surgery--report of a case].
AB  - We report a case of pulmonary mucormycosis successfully treated by medical
      methods only. The patient was a 51-year-old man with diabetes mellitus who
      presented with general fatigue and appetite loss. His chest radiograph and CT
      scan showed multiple thin-walled cavities in the left upper lobe. Because we
      could arrive at a clear diagnosis, video-assisted thoracoscopic surgery was
      performed. Lung biopsy of the left upper lobe revealed pulmonary mucormycosis.
      Our diagnosis was pulmonary mucormycosis with diabetes mellitus and alcohol
      addiction. The patient was treated with antifungal drugs--mainly amphotericin-B-
      while the diabetes mellitus was well controlled, and his diet and nutritional
      state was improved, resulting in the disappearance of symptoms, improvement of
      the radiological findings, and the absence of any relapse of the disease of at
      least 3 years.

PMID- 12795189
TI  - [Relapsing polychondritis with idiopathic hypoparathyroidism].
AB  - A 49-year-old man who had been treated with vitamin D since idiopathic
      hypoparathyroidism (IPH) was diagnosed at age 15 was referred to our hospital
      because of progressive wheezing. The same condition was also diagnosed in his
      sister at age 19. Chest radiography and computed tomography (CT) showed diffuse
      tracheal stenosis to a diameter of 6-8 mm. Laryngoscopy revealed no abnormality
      in the patient's epiglottis or vocal cords. No intact parathyroid hormone was
      detected in his sera but a brain CT scan showed calcification of the basal
      ganglia, which was compatible with IPH. Steroid therapy relieved his wheezing
      occasionally, but with little improvement of the narrowing of his trachea. He
      died of respiratory failure accompanied by lung abscess 15 weeks later. Autopsy
      revealed tracheal stenosis, thickening of the tracheal wall with marked fibrosis,
      and slight infiltration of inflammatory cells, which supported a diagnosis of
      relapsing polychondritis. This is the first report of relapsing polychondritis
      associated with IPH. Since both diseases are associated with autoimmune activity,
      this case may provide some insight into the pathogeneses of both diseases.

PMID- 12795190
TI  - [Two cases of intramedullary spinal cord metastasis of lung cancer detected with
      MRI].
AB  - We report two cases of intramedullary spinal cord metastasis of lung cancer
      detected by MRI. Case 1: A 77-year-old man underwent chemotherapy and left lower
      lung lobectomy for squamous cell carcinoma of the lung (T2N0M0). About one year
      later, he complained of paresthesia of the lower extremities and claudication on
      walking, and then of weakness of the lower limbs and bladder dysfunction.
      Magnetic resonance imaging (MRI) revealed an enhanced mass in the dural sac at
      the level of the spines of L1-2. Volume reduction surgery was promptly performed.
      The pathological diagnosis was squamous cell carcinoma. Case 2: A small cell
      carcinoma of lung with metastasis to bone, kidney and cerebellum (T4 N3 M1) in a
      73-year-old man was diagnosed. He showed a partial response to chemotherapies and
      to whole brain radiation (45 Gy). Three months later, he presented sudden onset
      paraplegia, paraesthesia and bladder dysfunction. MRI demonstrated an enhancing
      intramedullary lesion that delineated the conus of the cauda equina, and T 2
      weighted MRI images showed multiple nodules in sacs.

PMID- 12795191
TI  - [Introductions to systems biology].

PMID- 12795192
TI  - [System biological approach to research and treatment of brain tumors].

PMID- 12795193
TI  - [System analysis of circadian rhythms].

PMID- 12795194
TI  - [The ERATO Systems Biology Workbench and Systems Biology Markup Language: an
      integrated environment and standardization for systems biology].

PMID- 12795196
TI  - [Computer modeling of metabolic networks].

PMID- 12795195
TI  - [Simulation of IP3/Ca2+ signaling pathway in neurons: the system of coincidence
      detection of input timing in cerebellar Purkinje cells].

PMID- 12795197
TI  - [Training program for system biologists in Keio University].

PMID- 12795198
TI  - [Undergraduate program for bioinformatics and systems biology, graduate school of
      information science and technology, University of Tokyo].

PMID- 12795199
TI  - [Laboratory for systems biology and medicine at RCAST, University of Tokyo].

PMID- 12795200
TI  - [RIP(regulated intramembrane proteolysis): from bacteria to higher organism].

PMID- 12795201
TI  - [Introduction to comparative genomics].

PMID- 12795202
TI  - [Setsuro Ebashi, a pioneer of cell signal research].

PMID- 12795203
TI  - Francisco Varela (1946-2001): filling the mind--brain gap: a life adventure.
AB  - One of the most eminent neuroscientists recently passed away in Paris. Professor
      Francisco Varela was a scholar that approached science with a remarkably broad
      and integrative perspective, deeply contributing to a diversity of fields, from
      mathematics to epistemology, from immunology to neuroscience. He was strongly
      influenced by Buddhism and actively participated in unraveling the relationship
      between science and spirituality. This article introduces a special edition of
      Biological Research dedicated to the memory of this great man. It contains a
      collection of valuable contributions by various authors who collaborated with
      Varela at different moments of his outstanding scientific career. Their articles
      cover most of the fields in which he made contributions.

PMID- 12795204
TI  - For Francisco Varela: explorer of the phenomenal world.
AB  - Francisco Varela was an innovative thinker and researcher as well as a pioneer in
      the present dialog between science and Buddhism. In this essay, I will first
      speak briefly about some of Francisco's contributions to the world at large and
      then relate a few vivid moments from my own interactions with him.

PMID- 12795205
TI  - A walk with Francisco Varela from first- to second-generation networks: in search
      of the structure, dynamics and metadynamics of an organism-centered immune
      system.

PMID- 12795206
TI  - From autopoiesis to neurophenomenology: Francisco Varela's exploration of the
      biophysics of being.
AB  - This paper reviews in detail Francisco Varela's work on subjectivity and
      consciousness in the biological sciences. His original approach to this "hard
      problem" presents a subjectivity that is radically intertwined with its
      biological and physical roots. It must be understood within the framework of his
      theory of a concrete, embodied dynamics, grounded in his general theory of
      autonomous systems. Through concepts and paradigms such as biological autonomy,
      embodiment and neurophenomenology, the article explores the multiple levels of
      circular causality assumed by Varela to play a fundamental role in the emergence
      of human experience. The concept of biological autonomy provides the necessary
      and sufficient conditions for characterizing biological life and identity as an
      emergent and circular self-producing process. Embodiment provides a systemic and
      dynamical framework for understanding how a cognitive self--a mind--can arise in
      an organism in the midst of its operational cycles of internal regulation and
      ongoing sensorimotor coupling. Global subjective properties can emerge at
      different levels from the interactions of components and can reciprocally
      constrain local processes through an ongoing, recursive morphodynamics.
      Neurophenomenology is a supplementary step in the study of consciousness. Through
      a rigorous method, it advocates the careful examination of experience with first
      person methodologies. It attempts to create heuristic mutual constraints between
      biophysical data and data produced by accounts of subjective experience. The aim
      is to explicitly ground the active and disciplined insight the subject has about
      his/her experience in a biophysical emergent process. Finally, we discuss
      Varela's essential contribution to our understanding of the generation of
      consciousness in the framework of what we call his "biophysics of being."

PMID- 12795207
TI  - Disentangling the dynamic core: a research program for a neurodynamics at the
      large-scale.
AB  - My purpose in this paper is to sketch a research direction based on Francisco
      Varela's pioneering work in neurodynamics (see also Rudrauf et al. 2003, in this
      issue). Very early on he argued that the internal coherence of every mental
      cognitive state lies in the global self-organization of the brain activities at
      the large-scale, constituting a fundamental pole of integration called here a
      "dynamic core". Recent neuroimaging evidence appears to broadly support this
      hypothesis and suggests that a global brain dynamics emerges at the large scale
      level from the cooperative interactions among widely distributed neuronal
      populations. Despite a growing body of evidence supporting this view, our
      understanding of these large-scale brain processes remains hampered by the lack
      of a theoretical language for expressing these complex behaviors in dynamical
      terms. In this paper, I propose a rough cartography of a comprehensive approach
      that offers a conceptual and mathematical framework to analyze spatio-temporal
      large-scale brain phenomena. I emphasize how these nonlinear methods can be
      applied, what property might be inferred from neuronal signals, and where one
      might productively proceed for the future. This paper is dedicated, with respect
      and affection, to the memory of Francisco Varela.

PMID- 12795208
TI  - Long distance communication in the human brain: timing constraints for inter
      hemispheric synchrony and the origin of brain lateralization.
AB  - Analysis of corpus callosum fiber composition reveals that inter-hemispheric
      transmission time may put constraints on the development of inter-hemispheric
      synchronic ensembles, especially in species with large brains like humans. In
      order to overcome this limitation, a subset of large-diameter callosal fibers are
      specialized for fast inter-hemispheric transmission, particularly in large
      brained species. Nevertheless, the constraints on fast inter-hemispheric
      communication in large-brained species can somehow contribute to the development
      of ipsilateral, intrahemispheric networks, which might promote the development of
      brain lateralization.

PMID- 12795209
TI  - An "enactive" approach to integrative and comparative biology: thoughts on the
      table.
AB  - We discuss the concept of Enaction as originally proposed by Varela. We attempt
      to exemplify through two specific topics, sensory ecology and behavior, as well
      as physiological and behavioral ecology, on which the enactive approach is based.
      We argue that sensory physiology allows us to explore the biological and
      cognitive meaning of animal 'private' sensory channels, beyond the scope of our
      own sensory capacity. Furthermore, after analyzing the interplay between factors
      that may impose limits upon an animal's use of time and energy, we call for a
      program of research in integrative and comparative biology that simultaneously
      considers evolutionary ecology (including physiological and behavioral ecology)
      and neurobiology (including cognitive mechanisms as well structural design). We
      believe that this approach represents a shift in scientific attitude among
      biologists concerning the place of biological and ecological topics in studies of
      integrative and comparative biology and biological diversity and vice versa.

PMID- 12795210
TI  - Morphodynamical enaction: the case of color.

PMID- 12795211
TI  - Evolution of probability measures by cellular automata on algebraic topological
      Markov chains.
AB  - In this paper we review some recent results on the evolution of probability
      measures under cellular automata acting on a fullshift. In particular we discuss
      the crucial role of the attractiveness of maximal measures. We enlarge the
      context of the results of a previous study of topological Markov chains that are
      Abelian groups; the shift map is an automorphism of this group. This is carried
      out by studying the dynamics of Markov measures by a particular additive cellular
      automata. Many of these topics were within the focus of Francisco Varela's
      mathematical interests.

PMID- 12795212
TI  - Color vision in the comb frequency domain.
AB  - In 1982, Horace Barlow considered the question of human trichromacy in the
      context of information theory: according to the Sampling Theorem, three types of
      receptors covering the visible spectrum (400-700 nm) might be sufficient to
      reconstruct the color signal. Although Barlow was led to reject the direct
      application of the Sampling Theorem to explain color dimensionality, the
      theoretical framework offers a fresh point of view for analyzing the color system
      in conjunction with the physical characteristics of natural color signals. This
      review aims to illustrate that if the strict mathematical reconstruction (as
      implied by the Sampling Theorem) is replaced by a pragmatic approximation of
      color signals, then trichromacy, with its subsequent opponent-color process,
      could be regarded as an optimization of color constancy abilities in the spectral
      environment of primates. Higher dimension systems (tetrachromacy) found in other
      species can also serve the purpose of color constancy optimization in
      environments where color signals exhibit a finer spectral structure.

PMID- 12795214
TI  - [A research on fast-propagation of Pseudostellaria heterophylla].
AB  - The result of fast-propagation of Pseudostellaria heterophylla by tissue culture
      showed that the best explant was stem tip. It also showed the suitable inducement
      mediums were MS + 6-BA 2.0 mg/L + NAA 0.2 mg/L or MS + 6-BA 4.0 mg/L + NAA 0.4
      mg/L for the clustered bud, MS + 2,4-D 4.0 mg/L + Kt 0.5 mg/L or MS + 2,4-D 3.0
      mg/L + Kt 0.5 mg/L for the callus growth and 1/2 MS + NAA 0.3 mg/L for the root
      growth.

PMID- 12795213
TI  - [Observation and comparison of the flowers of Pogostemon cablin from different
      habitats].
AB  - The present work is concerned in the observation and comparison among the flowers
      of Pogostemon cablin (Blanco) Benth. from 3 different habitats by microscopical
      identification and electron microscopy scanning. The results provided scientific
      basis for recognition and distinction of Pogostemon cablin varieties.

PMID- 12795215
TI  - [Comparison of amino acid contents in Panax notoginseng from different habitats].
AB  - OBJECTIVE: To determine the contents of amino acid and study the characters of
      Sanqi (Panax notoginseng) from different habitats. METHODS: By Hitach 835-50
      amino acid anaylzer. RESULTS: 19 amino acid were extracted from root of P.
      notoginseng. The contents of Arg, Asp, and Glu are high. The beta-Ala and Orn
      were first separated from P. notoginseng. CONCLUSION: There were differences of
      the amino acid contents in Sanqi from different habitats. The sequence of its 3
      major amino acid contents were Arg > Asp > Glu, which can be considered as a
      character of Sanqi.

PMID- 12795216
TI  - [Research on microscopic structure of stem and leaf of Lysimachia decurrens].
AB  - OBJECTIVE: This paper reported microscopic characters of Lysimachia decurrens.
      The results showed that secretory canals were scattered in the cortex, pericycle
      fibres arrayed annularly and pith was large with many secreory canals in the
      transverse section of the stem. It also showed radiate cuticula grains and round
      oil cells were found in the upper epidermis cells of leaf, which was bifacial and
      contained two midrib vascular bundles, one much bigger than the other.

PMID- 12795217
TI  - [Direct identification of Celosia argentea from its confused species by FTIR].
AB  - OBJECTIVE: To directly and accurately identify Celosia argentea L. from its
      confused species. METHODS: Fourier Transform Infrared Spectrum. RESULT: Obvious
      characteristics for the identification in FTIR were revealed, which can be used
      to identify Celosia argentea L. and its confused species, such as Celosia
      cristata L., Amoranthus retroflexus. A. tricolor L. and A. patulus Bertol.
      CONCLUSION: Celosia argentea L. and its confused species were identified by FTIR
      directly, fastly and accurately.

PMID- 12795218
TI  - [Structural features of two neutral polysaccharides Md-1, Md-2 from Ophiopogon
      japonocus].
AB  - OBJECTIVE: To study the chemical feature of Md-1, Md-2 polysaccharides which
      extracted from Ophiopogon japonocus. METHOD: Two constituents were isolated and
      purified by gel-filtration chromatography. Physicochemical constants and spectral
      analysis further were used to study their structural features. RESULT: The mean
      molecular weights were estimated to be 27064 and 48651. Structures were composed
      of D-glucose. CONCLUSION: Md-1 and Md-2 polysaccharides are glucosans, which only
      are composed of D-glucose units joined by alpha-(1-->4) glucosidic linkages.

PMID- 12795219
TI  - [Analysis of the constituents of essential oils from Sambucus chinensis].
AB  - 26 chemical constituents of the essential oil from Sambucus chinensis Lindl. were
      separated and identified by GC/MS. The relative contents of them were determined
      by area nomalization.

PMID- 12795220
TI  - [The inhibitory effect of saponins from Tribulus terrestris on Bcap-37 breast
      cancer cell line in vitro].
AB  - The inhibitory effect of saponins from Tribulus terrestris (STT) on Bcap37 breast
      cancer cell line were determined by cell growth curve, MTT assay, protein content
      assay and morphological observation. The results showed that STT had potent
      inhibitory effect on Bcap-37 cell line in a concentration-dependent manner. Bcap
      37 cell exhibited morphological alteration, namely, cells got round and shrunk,
      nuclei contracted after treating with STT.

PMID- 12795221
TI  - [The inhibitory effect of extracts from Galla chinensis on marine fouling
      bacteria].
AB  - OBJECTIVE: To observe the activity of extracts from Galla Chinensis with
      different solvents against marine fouling bacteria in vitro. METHOD: Incubating
      plate with foveolae was used. RESULTS: The ethyl acetate, ethanol and water
      extracts showed strong inhibitory activity against marine fouling bacteria
      belonging to nine genera including Pseudomonas, Aeromonas, Alealigenes,
      Flavobacterium, Vibrio, Photobacterium, Moraxella, Chromobacterium, Enterobacter.
      While, the petroleum ether and chloroform extracts showed no inhibitory activity.
      CONCLUSION: The study provided theory basis for new biologic protective dope on
      environment.

PMID- 12795222
TI  - [The effect of the extract from Radix Paeoniae alba on IgA Glomerulonephritis in
      mice].
AB  - OBJECTIVE: To observe the effect of the extract from Radix Paeoniae Alba on IgA
      glomerulonephritis in mice. METHODS: IgA glomerulonephritis was induced by
      injection of dextran and sephadex-150. After administrating the extract, the
      contents of urinary protein, BUN and Cr in serum were determined. RESULTS: The
      extract could inhibit the decline of mouse weight, and decrease urinary protein
      content and BUN content in serum. While, the extract had no effect on Cr in
      serum. CONCLUSION: The extract from Radix Paeoniae Alba had therapeutical effect
      on IgA glomerulonephritis.

PMID- 12795223
TI  - [Protective effect of ganmeiling injection on chronic hepatic injury in rats].
AB  - OBJECTIVE: To study protective effect of Injection Ganmeiling on chronic hepatic
      injury. METHODS: The activity of AST, ALT and ALP in serum and histopathological
      change were determined in hepatic injury rats induced by CCl4. RESULTS:
      Ganmeiling obviously inhibited the rising of AST, ALT and ALP in serum. The
      histopathological examination showed that Ganmeiling could alleviate the
      condition of necrosis and the degeneration of hepatic cells. CONCLUSION: The
      results suggested that Ganmeiling could protect liver from hepatic injury induced
      by CCl4.

PMID- 12795224
TI  - [Study on chitosan clarification refining the decoction of jiangtangtongmai by
      homogenous design method].
AB  - OBJECTIVE: To study the effect of chitosan clarification refining the decoction
      of Jiangtangtongmai by homogenous design method. METHODS: The content of catalpol
      in the refined decoction by the alcohol-precipitation method and chitosan
      clarification method was determined by RP-HPLC. RESULTS: Catalpol can be well
      preserved by chitosan clarification method. CONCLUSION: Chitosan clarification
      method can replace alcohol-precipitation method in refining of the decoction of
      Jiangtangtongmai.

PMID- 12795225
TI  - [Study on quality standard for heshouwu dispensing granule].
AB  - OBJECTIVE: To study the quality standard for Heshouwu dispensing granule.
      METHODS: Heshouwu dispensing granule was identified by TLC and 2,3,5,4'
      tetrahydroxy-stilbene-2-O-beta-D-glucoside in Heshouwu dispensing granule were
      determined by HPLC. RESULTS: The linear relationship was at the range of 0.4028
      3.6252 micrograms and the average recovery was 101.15%, RSD = 2.00% for 2,3,5,4'
      tetrahydroxy-stilbene-2-O-beta-D-glucoside. CONCLUSION: The methods were
      available with a good reproducibility and can be used to control the quality of
      Heshouwu dispensing granule.

PMID- 12795226
TI  - [A herbalogical study on traditional Mongolian medicine "zhanba"].
AB  - By herbalogical study and investigation, "Zhanba" used by Mongolia doctors mainly
      contains 7 species from 3 genera of 1 family, but "Zhanba" in Inner Mongolia
      Standard of Medicinal Materials only contains 3 species which are Althaea rosea,
      Malva sylvestris L. var. mauritiana and M. verticillata.

PMID- 12795227
TI  - [Clinical study on Tianbaokang injection against oxidative injury of vascular
      endothelial function in ischemic apoplexy].
AB  - OBJECTIVE: To discuss clinical effects and therapeutic mechanisms of Tianbaokang
      Injection on ischemic apoplexy. METHODS: 70 cases of ischemic apoplexy were
      divided into two groups at random(Tianbaokang group and contrast group, 38 and 32
      cases respectively). Clinical effects and indexes of hemorheology and vascular
      endothelial oxidative injury(SOD activity, MDA content, NO level and ET-1
      concentration). RESULTS: The efficiency of Tianbaokang on ischemic apoplexy was
      92.1%. Tianbaokang can improve indexes of hemorheology, decrease plasm MDA and ET
      1 content, and increase SOD activity and NO level obviously. CONCLUSION:
      Tianbaokang has better effects on ischemic apoplexy. The therapeutic mechanisms
      may be related to improving hemorheology, inhibiting lipid peroxidation and
      vascular endothelial injury, and regulating endothelial function.

PMID- 12795228
TI  - [Drainage of pathologic fluid collections under CT guidance].
AB  - During the period from January 2000 to November 2001 the authors performed in 98
      patients 129 drainages of pathological fluid collections. In all instances the
      drainages were performed under CT control. In 80 patients the drain was placed in
      the area of the pleural cavity, in 47 in the area of the peritoneal cavity and in
      three patients the localization was different. For drainage they used catheters
      of the pigtail type size from 8F to 24 F, depending on the extent of the
      pathological collection, its depth, and nature of the drained contents. In 119
      cases Seldinger's method was used, in 10 the tandem troacar method of placement
      of drainage catheters. The placement of the drainage catheter under CT control is
      a safe and effective method for removal of pathological fluid collection. In the
      authors' group successful drainage was proved in 71 of 84 (84.5%) patients
      followed up on a long-term basis.

PMID- 12795229
TI  - [Personal experience with injuries of the rectum and anus].
AB  - Authors analyze some new knowledge in treatment of rectal and anal injuries
      proceeded from own clinical experience in comparison with studies of a range of
      foreign authors published recently. During last ten years together 24 injured
      patients with this diagnose were operated in Traumatological Hospital Brno,
      primary reconstruction was performed in 10 patients, secondary reconstruction
      after precise examination of pelvic fundus pathophysiology in 14 patients, mostly
      transferred from other clinics. Authors prefer primary treatment in 3 hours after
      injury. This opinion is supported by control examinations after performed
      reconstructions.

PMID- 12795230
TI  - [Manually-assisted laparoscopic nephrectomy in a living donor].
AB  - Manually assisted laparoscopic nephrectomy from a live donor combines the
      advantage of a mini-invasive approach with the advantage of the assisting hand in
      the abdominal cavity to which the surgeon is used from classical operations. The
      authors performed the first nephrectomy from a live donor by this method on May
      13, 2002. Our initial experience with five nephrectomies by this method indicate
      that every subsequent operation was shorter and the period of warm ischemia was
      also shorter. There was no postoperative complication. In the second operation
      suppuration of the minilaparotomy occurred which protracted hospitalization and
      the convalescent period. The prerequisite of these operations is a certain amount
      of experience with laparoscopic operations. This type of nephrectomy has the
      general advantages of a miniinvasive approach, i.e. greater postoperative comfort
      and a shorter convalescence as compared with an open operation. The period of
      warm ischaemia does not differ markedly from nephrectmies by the classical
      procedure.

PMID- 12795231
TI  - [Pigmented hepatocellular adenoma of the liver caused by long-term use of
      phenobarbital].
AB  - A 28-year-old female patient was operated on account of symptomatic
      hepatocellular adenomas of the liver. Tumours with a diameter of 10 x 11 cm in
      the left lobe and 9 x 7 cm in the right lober were extirpated. In the adenomas
      non-ferric pigment resembling the pigment in Dubin-Johnson's syndrome was
      detected. The patient did not use contraceptives and was treated for more than 10
      years for epilepsy. The size, pigmentation, frequency of adenomas and absence of
      contraceptives in the case-history made the authors consider another aetiology of
      these adenomas. The authors discuss the possible development of adenomas of the
      liver as a result of long-term use of phenobarbital. As a basis they use
      experimental observations where this drug acts as a strong promotor of DNA
      synthesis and leads to the development of multiple adenomas and carcinomas in the
      liver of rats and mice.

PMID- 12795232
TI  - [Splendors and difficulties in modern medicine (modest observations of a
      layman)].

PMID- 12795234
TI  - [Long-term results of surgical treatment in lung cancer].
AB  - The surgical treatment of lung cancer has got a long tradition at our department.
      The aim of this work is to evaluate the group of 3,857 patients from the years
      1948-1997. The special analysis has been performed of the group of 1572 patients
      from the years 1974-1997 undergoing lung resection. Evaluating our operation
      policy a strong trend from pneumonectomy to less extensive operations can be
      found. The introduction of bronchoplastic operations and modern diagnostic
      methods has substantially improved the possibility of surgical treatment. The
      utilization of TNM system enabled to compare the different groups of patients
      according to the unified classification. The long term survival was directly
      related to the stage and histological type of disease. The five years period
      survived 33% of patients in whom the lung resection was performed during the
      period 1974-1997. The operative hospital mortality has been substantially reduced
      to 1.7%. Even though it is our duty to provided the surgical treatment to all the
      patients if the resection is still possible the best results are to be expected
      in patients in the first stage of disease. Therefore the early diagnosis followed
      by adequately sized resection without delay offers the best chance for the
      patients long term survival.

PMID- 12795233
TI  - [Tracheobronchial injuries--experience with diagnosis and therapy].
AB  - The incidence of penetrating injuries of the respiratory pathways is permanently
      low and relatively stable, on the other hand, it may be assumed that there is an
      increasing rate of tracheobronchial injuries during blunt accidents of the chest
      in particular in conjunction with the increased rate of traffic injuries. Serious
      injuries are involved, in particular because of their high morbidity and
      mortality; frequently they are part of associated injuries and polytraumas. In
      1999-2002 at the Surgical Clinic of the Plzen-Lochotin Faculty Hospital a
      penetrating stab wound of the cervical trachea was treated in an 11-year-old boy
      and injuries of the large bronchi of adult men resulting from blunt chest
      injuries during car accidents. All three injuries were associated with a typical
      symptomatology of pneumocolon and pneumomediastinum, or persistent pneumothorax
      and respiratory complaints resp. The definite diagnosis was established in two
      instances shortly after admission, based on results of CT and bronchoscopic
      examination, in the case of the injury of the middle bronchus only on the
      following day during surgical revision combined with preoperative bronchoscopy.
      Treatment was surgical in all instances. Twice the lesion was sutured, in one
      case pulmonary resection was performed. No significant postoperative
      complications were observed nor any deaths. The main factors which influence in a
      decisive way the prognosis of the casualty and the therapeutic result are in the
      authors' opinion, consistent with data in the literature, early assessment of the
      diagnosis of tracheobronchial injury and early adequate therapeutic action. In
      the diagnosis a dominant position is held in addition to CT in particular by
      treacheobronchoscopy. In case of surgical treatment reconstruction operations are
      preferred.

PMID- 12795235
TI  - [Control of blood loss with topical administration of aprotinin after pulmonary
      tissue decortication and pleurectomy].
AB  - The authors were prospectively monitoring postoperative blood loss in 23
      patients, in which decortication of the lung tissue and pleurectomy was performed
      and in which 500,000 KIU of aprotinin was applicated locally to the operating
      field before closing chest. The study was performed between the years 1998 and
      2001. The amount of blood loss was compared to that of a group of 23 patients who
      underwent the same type of surgery between 1991 and 1998 without use of
      aprotinin. The postoperative blood loss was monitored 6, 12 and 24 hours after
      completing the surgery. Postoperative blood loss was lower in the group of
      patients in which aprotinin was used which was found to be statistically
      significant compared to the group of nonaprotinin patients.

PMID- 12795236
TI  - [Pseudoaneurysms due to iatrogenic arterial injuries--observations at a vascular
      surgery worksite].
AB  - With advancing care of patients with cardiovascular diseases the number of
      invasive cardiological operations is increasing. Although effective methods are
      involved, these procedures are also associated with certain risks for the
      patient. From the aspect of vascular surgery the most frequent complications
      include iatrogenic pseudoaneurysms and extensive haematomas. The objective of the
      present work is to evaluate the development of the number of pseudoaneurysms
      which occurred after puncture of the femoral artery during coronarography or
      PTCA, and verification of the hypothesis of the declining trend of the ratio of
      pseudoaneurysms in the total number of performed invasive cardiological
      diagnostic and therapeutic operations. The author submits in his paper the
      retrospectively assessed number of invasive operations performed at the 1st
      Medical Cardioangiological Clinic of the St. Ann Faculty Hospital Brno in 1996
      2001. It summarizes the number of PA dealt with during the same period by
      physicians of the 2nd Surgical Clinic of the St. Ann Hospital in Brno. It
      analyzes also the treated complications of cardiological operations in 2001.

PMID- 12795237
TI  - [Stenoses of the terminal choledochus--surgical treatment].
AB  - INTRODUCTION: Obstructive jaundice caused by stenosis of the terminal choledochus
      remains even nowadays a serious differential diagnostic and therapeutic problem.
      OBJECTIVE: The objective is to draw attention to possible contemporary treatment
      and its indications. MATERIAL AND METHODS: The authors evaluated retrospectively
      the results achieved by surgical treatment in 145 patients operated during the
      last 8 years on account of benign or malignant obstruction of the terminal
      choledochus. RESULTS: Within 30 days after surgery 9 patients (6%) died. A
      relapse of the obstructive jaundice occurred in three instances (2%). The
      morbidity amounted to a total of 14% and is comparable with data in the
      contemporary literature. CONCLUSIONS: The presented results support the inclusion
      of surgical treatment as the method of first choice in patients with stenosis of
      the terminal choledochus of uncertain biological nature. For surgery also
      patients are indicated with obstruction of malignant origin who cannot be treated
      radically (M1), provided they are in a satisfactory general condition (ASA I
      III). Surgical therapy is suitable also for treatment of the majority of patients
      with a benign stenosis or stricture of the terminal choledochus.

PMID- 12795238
TI  - [Indications for arthrodesis of the knee joint in modern orthopedics].
AB  - INTRODUCTION: Indication for arthrodesis of the knee joint is nowadays most
      frequently failure of a total endoprosthesis, usually septic. A less frequent
      indication is purulent gonitis, frequently after corticoid administration, the
      condition after a complicated intraarticular fracture with subsequent arthritis
      or oncological disease of the bones in the area of the knee joint. MATERIAL AND
      METHODS: In the course of 2000 to 2002 at the authors' department 15 arthrodeses
      were implanted. In three cases the indication for arthrodesis was purulent
      gonitis, in three cases the condition after an open articular injury associated
      with infectious complications and in the remaining nine cases failure of an
      endoprosthesis of the knee, incl. seven caused by infection. The patients were
      three men and 12 women, mean age 64 years (30-75 years). For stabilization of the
      arthrodesis 9x external fixation was used, 5x plates and 1x intramedullary
      osteosynthesis. RESULTS: In all cases consolidation of the arthrodesis was
      achieved. In one case the external fixation had to be replaced by a system of two
      fixation devices and in one case correction of the axial position of the
      extremity was made. The presence of external fixation was perceived negatively in
      particular by female patients. DISCUSSION: Plate osteosynthesis and the use of
      external fixation devices are relatively quick, cheap and considerate methods of
      arthrodesis. External fixation must be used in acute virulent infections while
      plate osteosynthesis can be indicated in its absence. The characteristic of
      intramedullary fixation is similar, however special nails used for arthrodesis of
      the knee are several times more expensive than the previous types of
      stabilization. The advantage is the possibility to use a massive bone graft to
      fill the defect.

PMID- 12795239
TI  - Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous
      and intramuscular administration.
AB  - Alefacept, human LFA-3/IgG1 fusion protein, is currently under clinical
      development for the treatment of chronic plaque psoriasis and other T cell
      mediated disorders. This recombinant protein binds CD2 on T cells and Fc gamma
      RIII on accessory cells (e.g., natural killer cells, macrophages), inhibiting T
      cell activation/proliferation and inducing selective T cell apoptosis. These
      effects are associated with selective reductions in memory-effector (CD4+ CD45RO+
      and CD8+ CD45RO+) T cells. Two open-label studies were conducted in healthy male
      volunteers to evaluate the pharmacokinetics, biologic activity, and tolerability
      of a single dose of alefacept when administered as a 0.15 mg/kg 30-sec i.v. bolus
      (n = 12), 0.04 mg/kg intramuscular (i.m.) injection (n = 8), or 0.04 mg/kg 30-min
      intravenous (i.v.) infusion (n = 8). i.v. infusion produced a higher Cmax (0.96
      +/- 0.26 mcg/ml vs. 0.36 +/- 0.19 mcg/ml) and a shorter Tmax (2.8 +/- 1.9 hr vs.
      86 +/- 60 hr) when compared to i.m. injection. Based on AUC0-last and AUC0
      infenity values, the relative bioavailability of i.m. to i.v. infusion was
      approximately 60%. After absorption from the i.m. injection was complete, the
      rate of alefacept elimination from the serum appeared consistent with the i.v.
      infusion half-life (approximately 12 days). Biologic activity was demonstrated by
      transient reductions in absolute number of CD2+ lymphocytes, with notable
      specificity for memory T-cell subsets. Alefacept was well tolerated; the most
      common adverse effects were headache, pharyngitis, rash, and myalgia. IM
      administration was not associated with significant local reactions. Results of
      these studies support i.v. bolus or i.m. administration of alefacept. An i.m.
      dose of approximately 150 to 200% of the i.v. dose is an appropriate and
      convenient alternative to i.v. administration.

PMID- 12795240
TI  - A system-approach method for the adjustment of time-varying continuous drug
      infusion in individual patients: a simulation study.
AB  - The aim of this simulation study was to present a system-approach method for
      adjustment of continuous drug infusions at time-varying rates, aimed at achieving
      and then maintaining required drug concentration-time profiles in patients. The
      method presented can be used for safe and cost-effective individualization of
      drug dosing by computer-controlled infusion pumps. Utilization of this method is
      exemplified by simulation experiments, aimed at adjusting continuous infusions of
      Factor VIII (FVIII) at time-varying rates, which would theoretically yield
      required concentration-time profiles of FVIII in hemophilia A patients over
      several days.

PMID- 12795241
TI  - Nonparametric AUC estimation in population studies with incomplete sampling: a
      Bayesian approach.
AB  - The estimation of the AUC in a population without frequent and/or fixed
      individual samplings is of interest because the number of plasma samples can
      often be limited due to technical, ethical and cost reasons. Non-linear mixed
      effect models can provide both population and individual estimates of AUC based
      on sparse sampling protocols; however, appropriate structural models for the
      description of the pharmacokinetics are required. Nonparametric solutions have
      also been proposed to estimate the population AUC and the associated error when
      particular sampling protocols are adopted. However, they do not estimate the
      individual AUCs and lack flexibility. Also a semiparametric method has been
      proposed for addressing the problem of sparse sampling in reasonably well
      designed studies. In this work, we propose and evaluate a nonparametric Bayesian
      scheme for AUC estimation in population studies with arbitrary sampling
      protocols. In the stochastic model representing the whole population, the
      individual plasma concentration curves and the "mean" population curve are
      described by random walk processes, allowing the application of the method to the
      reconstruction of any kind of "regular" curves. Population and individual AUC
      estimation are performed by numerically computing the posterior expectation
      through a Markov chain Monte Carlo algorithm.

PMID- 12795242
TI  - Use of prior information to stabilize a population data analysis.
AB  - When modeling new data with a complex population pharmacokinetic/pharmacodynamic
      model, there may not be sufficient information to obtain estimates of all
      parameters. In this case information from previous studies can also be used to
      help stabilize estimation. Using simulated data, we explored three different ways
      to do this. (i) Some parameter values were fixed to estimates obtained from
      earlier data. (ii) The earlier data were combined with the current data. (iii)
      The objective function based on the current data was augmented by a penalty
      function expressing summary information obtained from the earlier data. This last
      method is similar to the use of a Bayesian prior. It may be particularly useful
      when either the combined data set of method (ii) is very large and leads to large
      computation times or when the early data are not readily available. With this
      method, two different types of penalty functions were used. With our examples,
      the three methods all resulted in stabilized estimation. Methods (ii) and (iii)
      gave similar results for parameter and standard error estimation, especially with
      respect to fixed effects parameters. For hypothesis testing, results obtained
      with method (i) are very problematic. There are also problems with the results
      obtained with method (iii), but they are much less severe, and when the design
      for the earlier data is known, they can be corrected by using a computer
      intensive simulation test procedure.

PMID- 12795244
TI  - [Editorial comment: coronary bypass reoperations].

PMID- 12795243
TI  - [Editorial comment: left ventricular functions and collateral circulation in
      coronary artery disease].

PMID- 12795245
TI  - [Editorial comment: integrated backscatter of the left atrial spontaneous echo
      contrast, left atrial appendix function and tissue Doppler].

PMID- 12795246
TI  - [Editorial comment: ventricular arrhythmias in hypertensive patients].

PMID- 12795248
TI  - [Editorial comment: insulin resistance and cardiovascular diseases].

PMID- 12795247
TI  - [Editorial comment: surgical treatment of aortic coarctation].

PMID- 12795249
TI  - [Editorial comment: obesity, coronary risk and risk factors].

PMID- 12795250
TI  - [Editorial comment: mitral stenosis and pregnancy complications].

PMID- 12795251
TI  - [Editorial comment: does intermittent dobutamine treatment produce relief in
      dilated cardiomyopathy?].

PMID- 12795253
TI  - [Stress on the effects of sildenafil citrate (Viagra) on the cardiovascular
      system].

PMID- 12795252
TI  - [Study on hypertension optimal treatment (HOT) and its inspiration].

PMID- 12795254
TI  - [Knowledge upgrade yourself to meet the new challenge].

PMID- 12795255
TI  - Endodontic and surgical treatment of a geminated maxillary incisor.
AB  - AIM: A geminated maxillary incisor required complex multidisciplinary treatment
      to preserve health and restore aesthetics. This report describes the coordination
      of coronal division, root extraction, bone grafting, endodontic treatment and
      orthodontics in achieving treatment goals. It is the intention of this report to
      show how a difficult case could be managed by properly coordinated
      multidisciplinary care. SUMMARY: Pulp testing of the geminated central right
      maxillary incisor gave a normal response. Radiographic investigation indicated a
      connection of the pulp chambers. Both the mesial and distal root were filled with
      gutta-percha. The connection between the two root canals was sealed with a
      flowable dentine-bonded resin. After dividing the crown with a diamond bur, the
      mesial part of the tooth was removed and the extraction socket was filled with
      beta-tricalcium phosphate ceramic (Cerasorb). Radiographs taken immediately after
      surgery and after 6 months showed no periodontal or periapical lesions. No signs
      of external resorption were identified. The diastema between the central incisors
      was closed by orthodontic treatment. KEY LEARNING POINTS: Geminated teeth may
      present aesthetic and functional problems which require multidisciplinary care.
      Careful clinical and radiographic examination is essential to decide on the fate
      of the coronal and root halves involved. A proper coordination between endodontic
      and surgical treatment may result in maintaining one tooth half, even if a
      midroot connection between the pulp chambers becomes evident. Orthograde
      endodontic treatment, hemisection and orthodontics may solve the aesthetic
      problem of a geminated tooth.

PMID- 12795256
TI  - [Inflammation of airway and chronic obstructive pulmonary disease].

PMID- 12795257
TI  - [Psychosomatic disease threatening the health of the people].

PMID- 12795258
TI  - [Toward gastric mucosa-related lymphatic tissue lymphoma].

PMID- 12795259
TI  - [Gastrointestinal peptide hormones: clinical application and basic study].

PMID- 12795260
TI  - [Changing the diagnostic criteria for diabetes mellitus awaits further study].

PMID- 12795261
TI  - [The rational use of fluoroquinolones].

PMID- 12795262
TI  - Major ongoing stroke trials.

PMID- 12795264
TI  - [Cerebrospinal fluid examination: is still an important in clinical diagnosis?].

PMID- 12795263
TI  - [Report of the 55th meeting of the American Academy of Neurology. Honolulu, March
      29-April 6, 2003].

PMID- 12795265
TI  - [Multiple disciplines in the treatment of nervous diseases in the elderly].

PMID- 12795266
TI  - [More attention to the diversity of clinical outcome in Helicobacter pylori].

PMID- 12795267
TI  - [Emphasizing the clinical study of spondyloarthropathies].

PMID- 12795268
TI  - [Infectious diseases and communicable diseases].

PMID- 12795269
TI  - [Current status and prospects of TT virus].

PMID- 12795270
TI  - [Choroidal melanoma in China: basic and clinical research].

PMID- 12795271
TI  - [Uveal melanoma: clinicopathological characteristics and differential diagnosis].

PMID- 12795272
TI  - [Radio-adhibition therapy of uveal melanoma: current status].

PMID- 12795273
TI  - [The laboratory breeding of lice].
AB  - The breeding of lice started in Poland as R. Weigl used to prepare a typhus
      vaccine from the guts of infected lice. Helene Sparrow introduced this breeding
      technique in the Institut Pasteur of Tunis in 1927. Lice will feed only on human
      blood. They were put in small wooden boxes with a thin cloth bottom through which
      they could bite and feed. Once a day the boxes were placed against the skin of
      human feeders whose role was essential in the process. The breeding of lice at
      the Institut Pasteur of Tunis lasted until 1980 and allowed significant advances
      in the study of typhus and relapsing fever.

PMID- 12795274
TI  - Factors associated with ambulatory care--sensitive hospitalizations among nursing
      home residents.
AB  - This study examined patient-level, facility-level, and area market-level factors
      affecting ambulatory care-sensitive hospitalization (ACSH) rates among nursing
      home residents. Although ACSH has long been used to monitor accessibility to
      health care services among community-dwelling populations, the use of ACSH rates
      as an indicator of potential quality-of-care problems affecting nursing home
      residents has not been employed. METHODS. Three years of quarterly Medicaid
      reimbursement data from more than 500 nursing homes were linked to 4 years of
      Medicare Provider Analysis and Review hospital claims data, nursing facility
      attribute data, and Area Resource File data to investigate the relative
      contribution of patient-, facility-, and market-level risk factors to ACSH among
      nursing home residents. RESULTS. Logistic regression results indicate that
      facility-level factors and nursing home quality-of-care indicators significantly
      contribute to the risk of ACSH. DISCUSSION. Findings underscore the need for
      continuing efforts to improve quality-of-care practices in nursing homes,
      particularly with respect to associations between quality-of-care indicators and
      facility structural/organizational characteristics with ACSHs.

PMID- 12795275
TI  - [Paul Voivenel].
AB  - Paul Voivenel was a highly talented neuro-psychiatrist whose lectures and medical
      articles gave him a sound reputation. As a writer he paid attention to all sides
      of human life and worked with happy and generous enthusiasm. After World War I he
      carried on with working in the Military Health Department of War in favour of War
      Veterans' healthcare. His motto was "Ad vitae gloriam".

PMID- 12795276
TI  - Predictors of older adults' capacity for medication management in a self
      medication program: a retrospective chart review.
AB  - The aim of this project was to identify variables that predicted older adults'
      ability to manage medications. METHODS: The study used a retrospective cohort
      design and was set in a self-medication program within a rehabilitation hospital.
      A random sample of charts from 301 participants in the self-medication program
      was reviewed. RESULTS: Logistic regression models accounted for 26.7% and 55.8%
      of the variance in the probability of making one or more self-medication errors
      during the initial and final weeks of the program, respectively. The importance
      of cognition in predicting medication management capacity was seen in bivariate
      and multivariate analyses and through a number of interactions with other
      predictors. Statistically significant predictors in one or both analyses included
      medication regimen complexity, Mini-Mental State Exam (MMSE) score, duration of
      institutionalization, depression, and interactions between (a) medication regimen
      complexity and MMSE score and (b) ability to cook and MMSE score. DISCUSSION: The
      direct effects of cognition and medication regimen complexity were important
      predictors of medication management capacity.

PMID- 12795277
TI  - [Centenary of Victor Segalen's thesis].
AB  - Victor Segalen has attended his thesis of doctorate of medicine on January the
      29th, 1902, L'Observation medicale chez les ecrivans naturalists, known by the
      title Les Cliniciens es-lettres. In this thesis we analyse the medical
      observation of the death of Jules de Goncourt, according to Goncourt's Journal.

PMID- 12795278
TI  - Home-and community-based alternatives to nursing homes: services and costs to
      maintain nursing home eligible individuals at home.
AB  - This study analyzes home- and community-based services (HCBS) use patterns and
      determines the costs of purchasing in-home services comparable to those offered
      by SCAN(R), a Social HMO. METHODS. Administrative data on 8,229 nursing home
      certifiable members were used to profile use patterns; a telephone survey
      gathered data on the market value of these services. RESULTS. Frail Social HMO
      members used a variety of HCBS to remain independent at home. These individuals
      would spend an average of $4,900 out of pocket per year to purchase equivalent
      HCBS, if they were not enrolled in the Social HMO. DISCUSSION. Findings suggest
      that the costs of maintaining a Social HMO member at home are modest and
      affordable, yet offer a substantial benefit, particularly to low- and moderate
      income older people. With the aging of the population, an integrated medical and
      social program, such as the Social HMO, offers a viable policy solution.

PMID- 12795279
TI  - Alcohol, aging, and cognitive performance: a cross-cultural comparison.
AB  - This study investigated the relationship between alcohol consumption and
      cognitive performance in two culturally diverse community-based populations.
      METHODS. A cross-sectional analysis was used including Japanese Americans (n =
      1,836) and Caucasians (n = 2,581) aged 65 and older. Cognitive performance was
      measured using the Cognitive Abilities Screening Instrument (CASI) (0 to 100
      point scale) and reaction time. RESULTS. Multivariate analysis revealed
      significant cultural and gender differences with cognitive performance. Compared
      to abstainers, Caucasian drinkers scored higher than Japanese American drinkers
      on the CASI (adjusted means = 93.4 versus 91.6). In contrast, Japanese American
      drinkers scored faster than Caucasian drinkers on choice reaction time (adjusted
      means = 505 versus 579 milliseconds). DISCUSSION. Results showed that current
      drinking was associated with better cognition in both the Caucasian and Japanese
      American groups. Longitudinal studies are needed to support the possible
      protective effects of alcohol on cognition and explore whether culture may modify
      this apparent benefit.

PMID- 12795280
TI  - The association of disability, sociodemographic background, and social network
      type in later life.
AB  - The article examines the association of disability and sociodemographic
      background with the type of social network in which elders are embedded and
      considers the implications of such associations for network continuity. METHODS.
      Secondary analysis of data from a national probability sample of Jewish adults
      aged 60 and older in Israel (N = 2,079) was used. Multinomial logistic regression
      analysis was employed to predict membership in different network types. RESULTS.
      Higher education predicted membership in friends networks. Female gender,
      Asian/African origin, low income, and disability were associated with neighbors
      networks. Family networks were predicted by Asian/African origin, less education,
      younger age, and disability. Restricted networks were associated with lower
      income and disability, and particularly by the interaction of age and disability.
      DISCUSSION. The findings suggest that network stability is most jeopardized when
      the oldest old become disabled. The social care needs of this latter group will
      continue to demand public attention.

PMID- 12795282
TI  - Thinking ahead: factors associated with executing advance directives.
AB  - This article examines why older adults do or do not execute advance directives.
      METHODS. Secondary data analysis was conducted on data from the Charlotte County
      (Florida) Healthy Aging Study, on 451 adults who were relatively healthy and
      affluent. Exploratory logistic regressions were conducted on the probability that
      respondents had executed advance directives. RESULTS. Findings indicated that
      increasing age and higher income were the most consistent indicators of having
      executed an advance directive. Also, individuals reporting taking more
      prescription medications were more likely to have all the advance directives,
      except the durable power of attorney for health care. Reporting more negative
      life events was predictive of having executed the durable power of attorney for
      health care. DISCUSSION. These findings suggest that in addition to awareness of
      advance directives, demographic, health, and situational factors may affect the
      willingness of older adults to execute advance directives. Further research
      should examine other, more representative, samples to confirm these findings.

PMID- 12795281
TI  - Semi-automated analysis of color M-mode echocardiographic images for determining
      transmitral pressure gradients using a simplified Euler equation.
AB  - We hypothesize that a simplified version of the Euler equation (SEE) utilizing
      differences in velocity over a distance and time as obtained by Color Doppler M
      mode (CMM) echocardiography can approximate actual peak transmitral pressure
      gradients deltaP(TM). METHODS: In 14 patients undergoing open-heart surgery,
      deltaP(TM) was measured under various hemodynamic conditions using 2 high
      fidelity transducers, 5 cm apart. Transesophageal CMM images were simultaneously
      acquired and a customized image analysis application was used to abstract
      spatiotemporal velocity characteristics. Using both the SEE and a simplified
      Bernoulli equations, deltaP(TM) were determined and compared to the actual
      deltaP(TM). RESULTS: While the simplified Bernoulli equation resulted in a poor
      estimate (y=0.075x+0.71, r=0.45), the deltaP(TM) obtained using the SEE
      correlated strongly (y=0.79x+0.48, r=0.91) with the actual measurements.
      CONCLUSIONS: Semi-automated analysis of CMM images using a SEE can accurately
      estimate actual deltaP(TM).

PMID- 12795283
TI  - Agreement reached on Framework Convention.

PMID- 12795284
TI  - Cancer control in an expanded Europe.

PMID- 12795285
TI  - Sign on and eLearn.

PMID- 12795286
TI  - [Study on postgenomics in diagnosis and treatment of tuberculosis: effect and
      perspective].

PMID- 12795287
TI  - [Rapid detection and assessment of drug susceptibility of Mycobacterium
      tuberculosis].

PMID- 12795288
TI  - [Outdoor air pollution and asthma].

PMID- 12795289
TI  - [Strengthening research on etiology and treatment of irritable bowel syndrome].

PMID- 12795290
TI  - [New concepts in diagnosis and treatment of chronic constipation].

PMID- 12795291
TI  - [Nuclear factor-kappaB and inflammatory bowel disease].

PMID- 12795292
TI  - [Research on thrombotic thrombocytopenic purpura].

PMID- 12795293
TI  - [New cognition of diagnosis and classification in myelodysplastic syndromes].

PMID- 12795294
TI  - [Enhance the research of hematopoietic stem cell applying].

PMID- 12795296
TI  - Public health. Street smart.
AB  - It can be difficult to reach people in their teens and early 20s with overt
      public health messages. Borrowing some of the messages and mediums of
      'alternative culture' marketing can be more effective. It is possible to organise
      large-scale events cheaply with the right funding and entertainment partners.

PMID- 12795295
TI  - Reform club. Interview by Alastair McLellan.

PMID- 12795297
TI  - Surgery or conservative treatment for acute achilles tendon ruptures: a meta
      analysis.

PMID- 12795298
TI  - Extracorporeal shock wave therapy for plantar fasciitis.

PMID- 12795299
TI  - Preparative purification of plasmid DNA templates for in vitro transcription
      assays by consecutive differential precipitations.
AB  - A procedure for large-scale isolation of plasmid DNA without the use of RNase has
      been developed to obtain a DNA template for preparative in vitro RNA synthesis
      catalyzed by phage RNA polymerases. The separation of plasmid DNA from admixtures
      has been achieved only through selective precipitations of either plasmid DNA or
      contaminants. No expensive reagents or equipment were required. Plasmid quality
      was evaluated by gel electrophoresis and restriction analysis. The obtained
      plasmid DNA templates have been shown to be devoid of any detectable
      ribonucleolytic activity that may interfere with the following RNA synthesis.

PMID- 12795300
TI  - Long-term prognosis for jumper's knee.

PMID- 12795301
TI  - Manual therapy, physical therapy, or care by a general practitioner for neck
      pain.

PMID- 12795302
TI  - Cell volume changes during rapid temperature shifts.
AB  - The effect of a rapid temperature increase on the volume of different types of
      cells was investigated. Experiments were carried out using continuous microscopic
      image analysis. Volume variation of yeast cells, yeast spheroplasts and human
      leukaemia cells was measured during the transient phase after a thermal shift.
      The thermal shift was found to induce rapid increase in cell volume for cells
      lacking a cell wall (yeast spheroplasts and human leukaemia cells). This increase
      in cell volume is assumed to be a main cause of the heat shock-induced cell
      death. A theoretical mechanistic model that explains the behaviour of these cells
      is finally proposed.

PMID- 12795304
TI  - [Editorial comment: myocardial texture analysis of diabetes].

PMID- 12795303
TI  - Women's knowledge of prenatal ultrasound and informed choice.
AB  - This study evaluated women's understanding of prenatal ultrasound in terms of
      meeting the requirements for informed choice. A cross-sectional survey was
      conducted to evaluate (1) how information is provided, (2) women's perceived
      value of the information received and, (3) their understanding of ultrasound in
      relation to the principles of informed choice. Women (n=113) completed a
      questionnaire prior to their 18-week ultrasound. Fifty-five percent stated they
      received no information from their care provider. Only 31.9% considered health
      care providers as a "very helpful" source of information. Yet, 69.0% stated their
      care provider gave them information that facilitated their understanding. Gaps
      were identified in women's understanding of ultrasound. Specifically, 46.0% did
      not view ultrasound as a screen for anomalies; some were uncertain about their
      safety (18.6%), diagnostic capabilities (26.5%), and limitations of testing
      (37.2%). These results suggest that women's understanding of ultrasound does not
      meet the requirements of informed choice.

PMID- 12795305
TI  - Antiperspirant drug products for over-the-counter human use; final monograph.
      Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule in the form of a
      final monograph establishing conditions under which over-the-counter (OTC)
      antiperspirant drug products are generally recognized as safe and effective and
      not misbranded as part of FDA's ongoing review of OTC drug products. FDA is
      issuing this final rule after considering public comments on its proposed
      regulation, issued as a tentative final monograph (TFM), and all new data and
      information on antiperspirant drug products that have come to the agency's
      attention.

PMID- 12795306
TI  - Medicare program; change in methodology for determining payment for
      extraordinarily high-cost cases (cost outliers) under the acute care hospital
      inpatient and long-term care hospital prospective payment systems. Final rule.
AB  - In this final rule, we are revising the methodology for determining payments for
      extraordinarily high-cost cases (cost outliers) made to Medicare-participating
      hospitals under the acute care hospital inpatient prospective payment system
      (IPPS). Under the existing outlier methodology, the cost-to-charge ratios from
      hospitals' latest settled cost reports are used in determining a fixed-loss
      amount cost outlier threshold. We have become aware that, in some cases,
      hospitals' recent rate-of-charge increases greatly exceed their rate-of-cost
      increases. Because there is a time lag between the cost-to-charge ratios from the
      latest settled cost report and current charges, this disparity in the rate-of
      increases for charges and costs results in cost-to-charge ratios that are too
      high, which in turn results in an overestimation of hospitals' current costs per
      case. Therefore, we are revising our outlier payment methodology to ensure that
      outlier payments are made only for truly expensive cases. We also are revising
      the methodology used to determine payment for high-cost outlier and short-stay
      outlier cases that are made to Medicare-participating long-term care hospitals
      (LTCHs) under the long-term care hospital prospective payment system (LTCH PPS).
      The policies for determining outlier payment under the LTCH PPS are modeled after
      the outlier payment policies under the IPPS.

PMID- 12795307
TI  - [Editorial comment: dobutamine stress echocardiography and dynamic left
      ventricular outflow tract gradient].

PMID- 12795308
TI  - The Resuscitation Greats. Nancy Caroline--from mobile intensive care to hospice.

PMID- 12795309
TI  - [Editorial comment: prediction of infarct-related artery in patients with acute
      inferior myocardial infarction and ST segment elevation].

PMID- 12795310
TI  - [Editorial comment: coronary bypass surgery in octogenarians].

PMID- 12795311
TI  - [Teaching propedeutics of internal diseases].

PMID- 12795312
TI  - Caring for all children.

PMID- 12795313
TI  - Continuing education and the practice of optometry.

PMID- 12795314
TI  - Top 10 most powerful foods for preserving sight.

PMID- 12795315
TI  - Accuracy of pharmaceutical tracking data with regard to optometrists'
      prescribing.
AB  - BACKGROUND: The optometric scope of practice has increased dramatically over the
      last 30 years. This includes the ability to administer legend drugs to facilitate
      the examination process and prescribe legend drugs to treat the eye and adjacent
      areas in accordance with state laws. However, because such laws are relatively
      new in some states, the prescribing optometric communities in the United States
      may have difficulty in making their presence known amongst the pharmaceutical
      tracking companies. This study looked at the relationship between prescriptions
      written and pharmaceutical tracking company outcomes. METHOD: Optometrists were
      recruited from five states--Florida, Illinois, Missouri, North Carolina, and
      Texas--to participate in this study. They represented urban and rural practices,
      group and solo practices, and multidisciplinary practices. They were requested to
      track all prescriptions they wrote for legend pharmaceutical drugs during the
      months of August, September, and October 2000, as well as the number of refills
      authorized. Numbers were obtained from a pharmaceutical tracking company for the
      same optometrists for the period July to September 2000, and October to December
      2000. The results reported by the optometrists were compared to the results
      provided by the pharmaceutical tracking company. RESULTS: There was a significant
      difference between the numbers reported as outcomes by the pharmaceutical
      tracking company and the self-reported prescriptions written. DISCUSSION: The
      current system for crediting prescriptions to optometrists seems to have some
      shortcomings. All parties involved must work to ensure that optometrists are
      being properly credited for the pharmaceutical prescriptions they write. Possible
      steps that may be taken by individuals, the optometric profession, and the
      pharmaceutical industry are discussed.

PMID- 12795316
TI  - Characteristics of urban Hispanic patients with diabetes presenting for eye care
      services.
AB  - BACKGROUND: Studies have demonstrated the differential impact of diabetic
      complications among Hispanic patients. This study profiles 50 patients seen in an
      urban optometric setting and compares them with a hospital-based ophthalmology
      clinic in the same community. METHODS: A sample of 50 Hispanic patients with
      diabetes was selected. Descriptive statistics were calculated and compared with
      the literature. RESULTS: Demographics show an equal split between genders, with a
      mean age of 52.7 years. Duration of diabetes ranged from 1 month to 22 years.
      Most patients had type II diabetes and were using oral hypoglycemics. Few had
      insurance coverage, with a wide range in time since last physical examination and
      last eye examination. Only 28% had an eye examination in the past year. The
      majority had good ocular outcomes. CONCLUSIONS: Compared with published reports
      from the literature, the patients in this sample were more likely to be male, and
      were less likely to have insurance and more likely to be newly diagnosed with
      diabetes. Patients in this sample were more likely to use oral hypoglycemics, and
      ophthalmic surveillance was more appropriate. While they were more likely to have
      had a previous eye examination, they were also more likely to have a BVA of 20/40
      or worse. This suggests that the patients seen in the optometric setting differ
      from those seen in the hospital-based clinic.

PMID- 12795317
TI  - The predictability of retention and discontinuation of contact lenses.
AB  - BACKGROUND: The objective of this research was to investigate the possibility of
      predicting the retention or discontinuation of contact lenses on the basis of
      their effect on the quality of life of the wearer. While most studies of
      discontinuation of assistive technology devices have focused on other than
      psychosocial causes of discontinuation, there is reason to believe that a major
      cause is the psychosocial effect of the device on the user. METHODS: Participants
      were 418 adult volunteers who had been fitted with contact lenses. One hundred
      eighty of the participants had discontinued wearing their lenses, while 238 were
      still wearing their lenses. The participants were asked to complete a recently
      developed questionnaire, the Psychosocial Impact of Assistive Devices Scales
      (PIADS), which measures the psychosocial impact of assistive devices, and is used
      also to predict retention and discontinuation of other assistive devices.
      RESULTS: Overall correct prediction of the 418 respondents was 68.9%. The PIADS
      was better at predicting discontinuation than retention among males, while the
      reverse was true for females. CONCLUSIONS: The PIADS was shown to be a valid
      instrument to predict retention and discontinuation of contact lenses.

PMID- 12795318
TI  - The symptomatic patient with normal phorias at distance and near: what tests
      detect a binocular vision problem?
AB  - PURPOSE: Patients often manifest symptoms that appear to be related to binocular
      distress. Many of these patients have normal heterophoria at distance and near,
      making the etiology of such symptoms perplexing. We performed a visual
      examination of patients having normal heterophoria at distance and near in order
      to investigate which visual analysis tests differentiate symptomatic from
      asymptomatic patients. METHODS: Eighty subjects (30 symptomatic, 50 asymptomatic)
      with ages between 18 to 35 years of either sex and any race were pooled based on
      vision-symptom level determined by a 9-question standardized visual-symptoms
      questionnaire scored using a 100-point scale (asymptomatic: score > or = 85;
      symptomatic: score < or = 75). Inclusion/exclusion criteria included vision
      correctable to 6/6 (20/20) Snellen acuity or better in each eye, normal phorias,
      no latent cyclovertical heterophoria, and normal ocular health. RESULTS: Of the
      30 symptomatic patients, 18 had reduced vergence facility response using 3 pd
      base-in/12 pd base-out loose prism at distance (n = 10; t-score = 2.41, p < 0.02,
      d = 76) and near (n = 15; t-score = 3.32, p < 0.01, df = 78) with a significant
      difference beyond the 0.02 level. No other test including measurement of
      accommodation, showed a significant between-group difference. However, three
      patients with normal vergence facility (distance and near) showed a reduced
      binocular accommodative facility response (+/-2.00 D at 40 cm). CONCLUSION: Given
      a patent with asthenopia, normal phorias, and visual acuity, a differential
      diagnosis may be made based primarily on using vergence facility and
      accommodative facility testing. From a clinical standpoint, the results expedite
      diagnosis of binocular vision abnormalities and direct treatment.

PMID- 12795319
TI  - Targeted rewards increase employee movation.

PMID- 12795320
TI  - Practice management by the numbers.

PMID- 12795322
TI  - Optometrists as employees: avoiding misconduct traps.

PMID- 12795321
TI  - Looking at the whole equation for quality vision.

PMID- 12795324
TI  - What is "business"?

PMID- 12795323
TI  - The challenge of the problem employee.

PMID- 12795325
TI  - Health outcomes assessment and economic evaluation in COPD: challenges and
      opportunities.

PMID- 12795326
TI  - COPD: problems in diagnosis and measurement.
AB  - Chronic obstructive pulmonary disease (COPD) is the most rapidly rising cause of
      death in individuals >65 yrs of age, the most rapidly growing segment of the USA
      population. Advancing the clinical research agenda for COPD entails careful
      consideration of several issues and problems: defining COPD, reliance on
      physiological testing, outcome measurements and comorbidities. In addition,
      issues pertaining to the recent dramatic increase in chronic obstructive
      pulmonary disease mortality in females, smoking susceptibility and the
      relationship of respiratory symptoms with hyperresponsiveness, as well as chronic
      obstructive pulmonary disease heterogeneity, are discussed.

PMID- 12795327
TI  - Methodological issues in evaluating measures of health as outcomes for COPD.
AB  - The selection of an appropriate outcome measure depends on the aspect of the
      disease being addressed and the purpose of the study being conducted. The most
      fundamental property of any outcome is its ability to measure the biological
      variable under question. Other properties such as discriminative and evaluative
      abilities are also important. Specific outcomes measure a single biological
      variable, such as forced expiratory volume in one second or depression. The
      specificity of such measures is attractive but requires precise definition of
      what is being measured and why. Other, summative, outcomes are used to quantify
      the overall effect of a number of different biological processes. The simplest
      summative measures are global questions such as "How would you rate your health
      overall?" Others are complex with many items. If designed and used correctly,
      these questionnaires can provide an estimate of the overall impact of disease or
      response to therapy and an index of whether that response was clinically
      worthwhile. Standardisation of measurements is important to permit comparisons
      between patients and studies, which makes the measurement of an individual's
      "quality of life" difficult. The term "health-status measurement" may be better
      when referring to the use of standardised questionnaires. Utility-based measures
      help address concerns regarding clinical versus statistical improvement and place
      outcomes for chronic obstructive pulmonary disease treatment trials in the
      context of all healthcare treatments.

PMID- 12795328
TI  - Airway inflammation in COPD: physiological outcome measures and induced sputum.
AB  - Chronic obstructive pulmonary disease (COPD) is a result of airway inflammation,
      and the best predictor of COPD is the early detection of airflow limitation by
      spirometry. The Global Initiative for Obstructive Lung Disease Workshop Report
      defines airflow limitation using simple spirometric indices. Available guidelines
      categorise the severity of COPD using forced expiratory volume in one second
      (FEV1) and forced vital capacity (FVC), with symptoms playing a minor role in the
      assessment. Current standards define COPD by progressive loss of FEV1, and thus
      longitudinal decline in FEV1 will be the primary outcome variable for
      intervention studies aimed at preventing or reducing the loss of pulmonary
      function. There is evidence, however, that the variable FEV1/FVC and FEV1 are
      often not measured properly in all settings. This article will discuss the roles
      of physiological measurements in diagnosing COPD and physiological outcome
      measures for COPD. It does not formally compare physiological measures with other
      outcome measures, such as symptoms or quality of life. Additionally, improved
      treatment of established disease requires a better understanding of the
      inflammatory process and its clinical effects and treatment. The inflammatory
      process, and how drugs affect it, can be studied noninvasively or relatively
      noninvasively by using refined methods of examining spontaneous or induced
      sputum. Enhanced understanding of the use of induced sputum will assist in
      predicting patients' responses to short- and long-term inhaled corticosteroid
      treatment, and the methods of sputum examination need to be simplified so that
      they can be applied more easily to clinical practice.

PMID- 12795329
TI  - The burden of illness and economic evaluation for COPD.
AB  - In today's cost-conscious environment, understanding the economic implications
      associated with disease processes and their treatments is as important as
      understanding their clinical impact. Medical expenditures for treating chronic
      obstructive pulmonary disease (COPD) and the indirect costs of morbidity can
      represent a substantial economic and social burden. Very little economic
      information concerning COPD is available, however, particularly outside of a few
      very well-developed Western nations. This article will provide an approach for
      conducting high-quality studies aimed at estimating the economic burden of
      chronic obstructive pulmonary disease and for making economic evaluations of
      healthcare interventions aimed at preventing and treating this disease.

PMID- 12795330
TI  - The assessment of health status among patients with COPD.
AB  - Survival and physiological measures alone do not represent the full experiences
      of patients with chronic obstructive pulmonary disease. Reducing the personal and
      social burden of disease by improving patients' symptoms, functional status and
      quality of life are also important goals. There has been a substantial increase
      in the use of newly developed tools that measure health status and it is
      important for clinicians and researchers to understand these instruments'
      strengths and weaknesses in providing insight into a patient's condition and
      experience. Relying only on mortality and physiological outcomes could blind a
      clinician to significant benefits patients may receive from a treatment. A
      growing body of research utilises end-points assessed directly by patients whose
      self-reported health status includes health-related quality of life and
      functional status. This article reviews major concepts and methods in health
      status assessments for patients with chronic obstructive pulmonary disease, which
      will have an important role in assessing the efficacy and effectiveness of new
      treatments.

PMID- 12795331
TI  - COPD exacerbations: definitions and classifications.
AB  - Chronic obstructive pulmonary disease (COPD) is defined independently of
      exacerbations, which are largely a feature of moderate-to-severe disease. This
      article is the result of a workshop that tried to define exacerbations of COPD
      for use in clinical, pharmacological and epidemiological studies. The conclusions
      represent the consensus of those present. This review describes definitions,
      ascertainment, severity assessments, duration and frequency, using varying
      sources of data including direct patient interview, healthcare databases and
      symptom diaries kept by patients in studies. The best general definition of a
      COPD exacerbation is the following: an exacerbation of COPD is a sustained
      worsening of the patient's condition, from the stable state and beyond normal day
      to-day variations that is acute in onset and may warrant additional treatment in
      a patient with underlying COPD. A more specific definition for studies where a
      bacteriological cause of exacerbation is being studied is included, as well as
      simpler definitions for retrospective identification from database sources.
      Prospective diary card assessments are best recorded as changes from an agreed
      baseline, rather than absolute symptom severities. Diary cards identify many
      unreported exacerbations, which on average have similar severities to reported
      exacerbations. A scale for exacerbation severity is proposed that incorporates in
      and outpatient assessments. Exacerbation duration, which also relates to
      severity, is defined from diary card reports. Healthcare utilisation is not an
      adequate substitute for severity, depending on many unrelated social and
      comorbidity factors. It is an outcome in its own right.

PMID- 12795332
TI  - New advances on prostate carcinogenesis and therapies: involvement of EGF-EGFR
      transduction system.
AB  - The prostate cancers (PCs) are among the major causes of death because
      therapeutic treatments are not effective against advanced and metastatic forms of
      this cellular hyperproliferative disorder. In fact, although androgen-deprivation
      therapies permit to cure localized PC forms, the metastatic PC cells have
      acquired multiple functional features that confer to them resistance to ionizing
      radiations and anticarcinogenic drugs currently used in therapy. The present
      review describes last advances on molecular mechanisms that might be responsible
      for sustained growth and survival of PC cells. In particular, emphasis is on
      intracellular signaling cascades which are involved in the mitogenic and
      antiapoptotic effects of epidermal growth factor EGF-EGFR system. Of therapeutic
      interest, recent advances and prospects for development of new treatments against
      incurable forms of metastatic PC forms are also discussed.

PMID- 12795333
TI  - Epidermal growth factor receptor: association of extracellular domain negatively
      regulates intracellular kinase activation in the absence of ligand.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in many types
      of human cancers. Receptor amplification, autocrine activation and/or deletion of
      exons 2-7 of EGFR gene have all been associated with tumor development. The
      traditional model of EGFR activation via ligand induced dimerization and
      consequential kinase activation does not provide full understanding of its
      tumorigenicity. The main function of the receptor extracellular domain (ECD) has
      been thought to be ligand recognition and binding. We report that the EGFR ECD,
      through its association also negatively regulates the activity of the
      intracellular kinase in the absence of ligand. Even in the absence of its
      ligands, the EGF receptor forms homodimers, however, the ECD prevents
      constitutive receptor kinase activation through its intrinsic ligand-independent
      interaction. The removal of this domain, either partial or total, results in
      constitutive activation of the receptor kinase as observed by its phosphorylation
      in intact cells. Furthermore, EGF receptors truncated in the ECD induce
      phosphorylation of the wild-type full-length receptor, indicating an inter
      molecular inhibitory mechanism by the receptor ECD. The tumor associated delta2
      7EGFR mutant also dimerizes with and phosphorylates the wild type EGFR in the
      absence of ligand. Thus, in addition to its role in ligand recognition, EGFR ECD
      interacts with each other, imposing an inhibitory effect on the activation of the
      intracellular kinase.

PMID- 12795334
TI  - Suppression of TNF-alpha mediated apoptosis by EGF in TNF-alpha sensitive human
      cervical carcinoma cell line.
AB  - The tumor suppressor protein p53 is the most frequently mutated gene in human
      cancer. The function of p53 is not restricted to "guarding" against oncogenic
      stress, but also p53 can guard against the presence of DNA damage. One of the
      principal mechanisms by which cells achieve this is by regulating the p53 protein
      level although its phosphorylation and cellular localization also contribute to
      the regulation of its function. Since many tumors secrete growth factor(s) that
      inhibit apoptosis and support the growth of cancer cells, we investigated the
      effects of human epidermal growth factor (EGF) on human TNF-alpha-mediated
      induction of p53 and its transcriptional target, p21 in TNF-alpha sensitive human
      cervical carcinoma cell line, ME180S. We found that TNF-alpha can increase the
      cellular levels of p53, p21 and induce apoptosis in ME180S cells. However,
      pretreatment of cells with EGF can suppress all these effects of TNF-alpha. To
      determine which kinase(s) pathway was utilized by EGF to show these suppressive
      effects, cells were pretreated with inhibitors of MAPK, PI3K and PKC pathways.
      Among these only PKC inhibitor reversed all the suppressive effects of EGF. We
      also found that ME180S cells express only zeta, lambda, epsilon, iota, delta,
      theta, beta PKC subtypes and among these EGF treatment activate only PKC-delta
      redistribution to the membrane from the cytosol. An inhibitor of PKC, GF 109203X
      inhibited EGF-mediated suppression of TNF-alpha-induced accumulation of p53, p21
      and induction of apoptosis. In summary, we concluded that EGF can protect ME180S
      cells from TNF-alpha-induced apoptosis through activation of PKC-delta.

PMID- 12795335
TI  - Expression of vascular endothelial growth factor isoforms in the Japanese quail
      embryo.
AB  - Vascular endothelial growth factor (VEGF) i s required for vascular development.
      In the quail, four VEGF isoforms formed by alternative splicing, are translated
      into proteins with 122, 146, 166, and 190 amino acids. VEGF isoforms differ
      biochemically, with variable affinities for heparan sulfate proteoglycans, the
      extracellular matrix and VEGF receptors. There are few data on the functional
      significance of VEGF isoforms. RT-PCR was used to examine isoform expression
      during quail vascular development. Our results suggest that all quail isoforms
      are expressed during establishment of the vascular pattern in whole embryos and
      extraembryonic tissues at apparently equal levels. No isoform-specific expression
      patterns were detected in isolated endoderm or between embryo halves.

PMID- 12795336
TI  - New prognostic factors and developing therapy of cutaneous melanoma.
AB  - The multiple molecular alterations underlying the neoplastic process and clinical
      characteristics of cutaneous melanoma are currently under intensive
      investigation. Recent studies have demonstrated that the levels of melanoma
      associated proteins in tumor tissue or in patient serum can serve as new markers
      to predict disease outcome. Similarly, the expression of thousands of genes in
      melanoma tumors can be surveyed simultaneously using DNA arrays, allowing
      molecular profiling of individual tumors, which gives the possibility of
      classifying melanomas based on their biological diversity. Large clinical studies
      have also identified multiple prognostic factors, such as tumor ulceration, and
      led to development of a new, more precise melanoma staging system, which
      emphasizes the biological characteristics of the primary disease. These new
      findings may have an important role in earlier measurement of the clinical
      response and provide a basis for tailored melanoma therapy, the development of
      which will also be discussed in this review.

PMID- 12795337
TI  - Adipogenesis: a cross-talk between cell proliferation and cell differentiation.
AB  - The transition between cell proliferation and cell differentiation taking place
      during adipocyte differentiation is a tightly regulated process where both cell
      cycle regulators and differentiating factors interact, creating a cascade of
      events leading to the commitment of the cells into the adipocyte phenotype. Based
      on in-vitro cell models of adipocyte differentiation, the different stages of
      adipogenesis have been established, each of them with a particular pattern of
      gene expression. Re-entry into the cell cycle of growth-arrested preadipocytes is
      known as the clonal expansion phase. Growth-arrested preadipocytes undergo
      several rounds of cell cycle before terminally differentiating into adipocytes,
      suggesting that a cross-talk might exist between the cell cycle or the cell
      proliferation machinery and the factors controlling cell differentiation. I will
      focus this review on the influence of the proliferative phase of preadipocytes in
      the adipocyte differentiation process.

PMID- 12795338
TI  - The neurodevelopmental hypothesis of schizophrenia: a review of recent
      developments.
AB  - The neurodevelopmental hypothesis (NDH) of schizophrenia suggests that a
      disruption of brain development during early life underlies the later emergence
      of psychosis during adulthood. The aim of this review is to chart the challenges
      and subsequent refinements to this hypothesis, with particular reference to the
      static versus progressive nature of the putative neurobiological processes
      underlying the NDH. A non-systematic literature review was undertaken, with an
      emphasis on major review papers relevant to the NDH. Weaknesses in the
      explanatory power of the NDH have led to a new generation of more refined
      hypotheses in recent years. In particular, recent versions of the hypothesis have
      incorporated evidence from structural neuroimaging which suggests changes in
      brain volumes after the onset of schizophrenia. More detailed models that
      incorporate progressive neurobiological processes have replaced early versions of
      the NDH, which were based on a 'static encephalopathy'. In addition, recent
      models have suggested that two or more 'hits' are required over the lifespan
      rather than only one early-life event. Animal models are providing important
      insights into the sequelae of disturbed early brain development. The NDH has
      provided great impetus to the schizophrenia research community. Recent versions
      of the hypothesis have encouraged more focused and testable hypotheses.

PMID- 12795339
TI  - Genetics of alcohol and tobacco use in humans.
AB  - The field of genetics holds great promise for furthering our understanding of the
      etiology of drug dependence and for identifying novel targets for treatment.
      Genetic studies utilizing twins and families have demonstrated a considerable
      role for genetics in nicotine and/or alcohol dependence. Risk for alcoholism or
      nicotine dependence is likely to be the result of a large number of genes, each
      contributing a small fraction of the overall risk. While this review will focus
      on studies in humans, many of the candidate genes for human nicotine and alcohol
      dependence listed here were originally postulated to be important, based on data
      from animal studies. The review will briefly summarize the results from twin and
      adoption studies that provide estimations of heritability, the results from
      chromosomal linkage studies that identify regions of chromosomes that may contain
      relevant genes, and the results of candidate gene studies. For each topic the
      data will be presented for nicotine dependence, alcohol dependence, and for
      nicotine and alcohol dependence together. In addition, each section will review
      briefly some of the confounding issues in the specific type of approach utilized.

PMID- 12795340
TI  - The future of psychiatric genetics.
AB  - Geneticists have been predicting that advances in their discipline will
      revolutionize the understanding of human disease and behavior. While there has
      been considerable progress in disorders showing simple, Mendelian patterns of
      inheritance, expectations have yet to be fulfilled for disorders and traits
      showing complex inheritance. In this article, we consider the difficulties that
      complex diseases pose to genetic research, discuss progress and make suggestions
      regarding future directions.

PMID- 12795341
TI  - Thromboxane antagonism and cough in chronic bronchitis.
AB  - BACKGROUND: The increased eicosanoid synthesis has been suggested as the
      underlying mechanism of chronic productive cough in patients with chronic
      bronchitis. METHOD: The effects of the orally active thromboxane A2 (TxA2)
      receptor antagonist seratrodast and the cysteinyl leukotrienes (cLTs) receptor
      antagonist pranlukast on cough response to inhaled capsaicin were examined in
      sixteen patients with stable chronic bronchitis. Capsaicin cough threshold,
      defined as the lowest concentration of capsaicin eliciting five or more coughs,
      was measured as an index of airway cough sensitivity. RESULTS: The cough
      threshold was significantly increased compared with placebo after four-week
      treatment with seratrodast, but not after treatment with pranlukast. CONCLUSIONS:
      TxA2, but not cLTs, may be a possible modulator augmenting airway cough
      sensitivity in chronic bronchitis. Thromboxane antagonism may be considered to be
      one of the therapeutic options for the treatment of chronic productive cough.

PMID- 12795342
TI  - Folate status and homocysteine level in Italian patients aged under 60 on oral
      anticoagulant therapy.
AB  - BACKGROUND: Folate deficiency occurs frequently and the related hyper
      homocysteinaemia is considered a risk factor for thrombosis. We investigated
      folate status and homocysteine (Hcy) concentration in patients under 60 years on
      oral anticoagulant therapy (OAT) for previous venous or arterial thrombosis and
      in healthy blood donors. PATIENTS AND METHOD: Thirty-nine patients (mean age 35.2
      years) on OAT for longer than 6 months and forty 44 healthy blood donors (mean
      age 36.0 years) were evaluated. Diet, serum folate (SF), red blood cell folate
      (RCF), homocysteinaemia, vitamin B12 levels and the mutation C677T of
      methylenetetrahydrofolate-reductase (MTHFR) gene were determined. RESULTS: The
      mean SF and Hcy concentrations were significantly higher in patients compared
      with blood donors (SF = 17.7 versus 10.5 nmol/L, P < 0.0001; Hcy = 11.7 versus
      8.9 micromol/L, P = 0.009). Twelve out of 39 patients and 7 out of 44 blood
      donors were homozygous for the mutation C677T of MTHFR gene. Among the remaining
      subjects, non-homozygous for the mutation, the patients (27) had mean SF and Hcy
      levels significantly higher than the (37) blood donors (SF = 18.1 versus 10.8
      nmol/L, P < 0.0001; Hcy = 10.3 versus 7.9 micromol/L P < 0.0006). CONCLUSION:
      Italian patients aged under 60 years on OAT and non-homozygous for the mutation
      C677T of MTHFR gene, had SF and Hcy concentrations significantly higher than the
      control group.

PMID- 12795343
TI  - Mutations in the p53 tumor suppressor gene in colorectal cancer in Taiwan.
AB  - Mutations in the tumor suppressor gene p53 have been reported as occurring
      prevalently in a wide range of human tumors. Detection of a mutated p53 is
      thought to provide useful information for the clinical management of colorectal
      neoplasm. In this study, we used polymerase chain reaction/single-strand
      conformation polymorphism (PCR/SSCP) and sequencing analysis to rapidly screen
      for mutations in p53 in colorectal cancer in Taiwan. Genomic DNA was purified
      from colorectal cancer specimens obtained from 80 patients at a teaching hospital
      in southern Taiwan. Primer sets were designed to amplify fragments within exons 4
      8 of p53. We found p53 mutations in 38 of 80 patients. This is the first
      identification of a mutation at codon 143 of p53 in colorectal cancer in Taiwan.
      In addition, we found two insertions in exon 5 of p53. The p53 mutation rate
      among colorectal tumors in Taiwan, found in this study, is 43%. The results
      indicate that p53 mutation is not significantly associated with tumor grade, age,
      or gender (p > 0.05). We found that two-fifths of colorectal cancer patients in
      Taiwan have a p53 mutation, which could be used as a marker of colorectal cancer.

PMID- 12795344
TI  - High cervical midline punctate myelotomy in the management of visceral pain in
      the mouse.
AB  - Increasing evidence implies the existence of a visceral pain pathway in the
      dorsal column of the spinal cord. Limited midline myelotomy has been used to
      treat intractable pelvic cancer pain. However, no obvious evidence has been
      provided that high cervical punctate midline myelotomy (CPMM) relieves visceral
      pain originating from the abdomen. This study was designed to examine the pain
      relief effect of CPMM in a mouse model of visceral pain. Thirty-six Institute of
      Cancer Research (ICR) mice were divided into three groups: Group 1, healthy
      controls; Group 2, treated with CPMM at C1 and C2; and Group 3, a sham group that
      underwent laminectomy at C1 and C2 without CPMM. All animals were tested for
      antinociception in the writhing test 24 hours after surgery. Visceral pain
      related behaviors were counted from 5-20 minutes after intraperitoneal injection
      of 0.6% acetic acid. Writhing test scores were not significantly different
      between Groups 1 (56.7 +/- 10.7) and 3 (50.7 +/- 17.4). However, Group 2 (30.0 +/
      14.3) showed more than 40% antinociception after treatment, and writhing test
      scores were significantly different from those of Groups 1 and 3 (p < 0.001). Our
      results confirm that midline punctate myelotomy can relieve visceral pain and
      imply that there is a pathway in the posterior funiculus that signals visceral
      pain. Punctate midline myelotomy at the cervical or high thoracic level may be an
      alternative strategy in the management of intractable visceral pain due to
      abdominal or pelvic cancers.

PMID- 12795345
TI  - Hearing loss in patients with nasopharyngeal carcinoma after chemotherapy and
      radiation.
AB  - In light of the possible adverse effects of radiation on hearing, we conducted a
      study to evaluate the long-term sensorineural hearing status following
      radiotherapy (RT) in patients suffering from nasopharyngeal carcinoma. Audiologic
      examinations were performed at regular intervals before and after RT. We also
      analyzed the effects of age, chemotherapy, pre-RT hearing status, and post-RT
      otitis media with effusion (OME) on post-RT hearing change. A total of 150
      patients (261 ears) were enrolled in this study and followed up for a mean of
      43.8 months. After RT, 8.9-28.8% of ears had at least a 10 dB loss in bone
      conduction threshold at speech frequency, which was defined as an average of
      hearing threshold at 0.5 kHz, 1 kHz, and 2 kHz, while the percentage was 18-34.2%
      at 4 kHz. Patient age was related to these changes at speech frequency, and the
      presence of post-RT OME was related to significant loss at both speech frequency
      and 4 kHz. Pre-RT hearing status and chemotherapy did not influence hearing
      change. To sum up, sensorineural hearing loss began as early as after completion
      of RT. Early changes may be transient, but the effect of radiation on hearing
      tended to be chronic and progressive.

PMID- 12795346
TI  - Patient- and family-rated scale for bipolar disorder symptoms: Internal State
      Scale.
AB  - The monitoring of patients, by themselves and their caregivers, is very important
      in the prophylaxis of bipolar disorder. This study aimed to develop a Chinese
      language version of an instrument for assessment of manic and depressive symptoms
      by patients and their families. Fifty-eight inpatients and outpatients with a DSM
      IV (Diagnostic and Statistical Manual of Mental Disorders) diagnosis of bipolar
      disorder were recruited. All subjects underwent clinical psychopathologic
      assessment by experienced psychiatrists using the Young Mania Rating Scale (YMRS)
      and the Hamilton Depression Rating Scale (HDRS). At the same time, each patient
      and key family members filled out the Chinese-language version of the Internal
      State Scale (ISS) for monitoring mental symptoms. Patients were examined a second
      time if they had entered remission or a new episode of the opposite polarity. The
      ISS was divided into two subscales, of well-being/activation and of irritability.
      Patients' well-being/activation and irritability subscales were significantly
      correlated with YMRS scores and the well-being/activation subscale was also
      significantly correlated with the HDRS score. Family members' irritability
      subscales were significantly correlated with HDRS scores only. The reliability
      and constructive validity of the ISS was good in both patients with bipolar
      disorder and their families.

PMID- 12795347
TI  - Acute thrombosis after elective direct intracoronary stenting in primary
      antiphospholipid syndrome: a case report.
AB  - Antiphospholipid syndrome (APS) is an uncommon prothrombotic disorder that has
      been increasingly recognized in recent years. The diagnosis of APS must be
      associated with venous or arterial thrombosis or both. Patients with APS usually
      present with recurrent deep vein thrombosis, pulmonary thromboembolism,
      thromboembolic stroke, or myocardial infarction. Here, we report a case of a 61
      year-old female who presented with a 3-month history of increasingly frequent
      retrosternal chest tightness. After treadmill test and thallium-201 myocardial
      perfusion scan, she was admitted and underwent elective coronary angiography but
      developed acute thrombosis after direct intracoronary stenting. She was
      successfully rescued with repeat percutaneous transluminal coronary angioplasty
      and prolonged heparin and glycoprotein IIb/IIIa antagonist use. Laboratory data
      showed prolongation of partial thromboplastin time and positive anti-cardiolipin
      antibody. These findings satisfied the criteria for APS; the patient was
      diagnosed with primary APS because she had neither typical symptoms nor signs of
      systemic lupus erythematosus or other immunologic disorders. Thereafter, long
      term oral anticoagulant appeared to be effective. To our knowledge, this is the
      first report of acute stent thrombosis in a patient with primary APS.

PMID- 12795348
TI  - Clubbed fingers and hypertrophic osteoarthropathy in a patient with squamous cell
      carcinoma of the lung.
AB  - Hypertrophic osteoarthropathy (HOA) is characterized by clubbed fingers and
      periosteal new bone formation. Etiologically, it can be divided into primary and
      secondary HOA, but its pathogenesis is uncertain. We report a 42-year-old male
      patient who suffered from painful clubbing fingers and toes. Serial examinations
      revealed periosteal new bone formation in the four limb long bones and a solid
      mass lesion in the right upper lung field. Pathologic examination of the resected
      mass lesion showed squamous cell carcinoma. After surgery and chemotherapy, the
      severity of clubbed fingers decreased and joint pain improved. Follow-up bone
      scan also suggested regression of the uptake of radioactivity in the four limb
      bones. We concluded that the HOA in this case was probably caused by lung cancer.

PMID- 12795349
TI  - Intramuscular metastasis of cutaneous squamous cell carcinoma: a case report.
AB  - Cutaneous squamous cell carcinoma (SCC) is a common cancer. Although most
      patients with primary cutaneous SCC have an excellent prognosis, for those with
      metastatic disease, the long-term prognosis is poor. The most common sites of
      metastasis are regional lymph nodes, lung, liver, brain, skin, and bone. However,
      metastatic soft tissue SCC from cutaneous lesions is extremely rare, with only
      two reported cases. We report a case in which the patient had a primary SCC
      lesion on his left palm in 1986. A second primary SCC on his left forearm was
      confirmed in 2001, with subsequent metastasis to the proximal muscles and bone
      invasion in spite of the initial wide excision.

PMID- 12795351
TI  - Differential diagnosis of tongue lesions.
AB  - This article reviews the clinical characteristics of the numerous local and
      systemic conditions that frequently involve the tongue and presents
      classifications based on their appearance and common locations that can aid
      dentists in their early recognition and clinical diagnosis.

PMID- 12795350
TI  - Diffuse cutaneous plasmacytomas demonstrated on gallium-67 imaging.
AB  - Gallium-67 scanning is a useful tool to search for infectious foci and malignant
      tumors. Multiple myeloma is one clinical indication for gallium-67 tumor survey.
      Here, we report a rare case of diffuse multiple cutaneous plasmacytomas from
      recurrent multiple myeloma, demonstrated by whole-body gallium-67 scan.

PMID- 12795352
TI  - Dental diseases in a Jordanian population on renal dialysis.
AB  - OBJECTIVE: The aim of this study was to examine the levels of periodontal disease
      and dental caries in individuals on renal dialysis in a Jordanian population.
      METHOD AND MATERIALS: A total of 47 individuals (mean age = 42.9 years, standard
      deviation [SD] 12.5) were examined for plaque deposits, gingivitis,
      periodontitis, and dental caries using the Silness and Loe plaque index (PII),
      Loe and Silness gingival index (GI), probing pocket depth (PPD), and decayed,
      missing, or filled teeth (DMFT), respectively. Gingival recession also was
      recorded using the distance from the cementoenamel junction to the gingival
      margin. Patients were categorized into three subgroups based on their renal
      dialysis histories: on dialysis for less than 1 year; on dialysis for 1 to 3
      years; or on dialysis longer than 3 years. RESULTS: There were no statistically
      significant differences in PII, GI, PPD, and gingival recession among the three
      subgroups examined. The GI revealed that 55% scored more than 2, indicating
      moderate to severe gingivitis. None of the individuals in this study displayed an
      absence of gingival inflammation. DMFT index showed that there were statistically
      significant differences between subjects on renal dialysis for less than 1 year
      and subjects on dialysis for 1 to 3 years and more than 3 years. The group DMFT
      index mean was 8.5 (SD 2.88). CONCLUSION: Gingival and dental diseases are
      prevalent in the renal dialysis population. The dental community's awareness of
      the implication of poor oral health within this population should be elevated and
      daily oral health maintenance should be reinforced by the dialysis team.

PMID- 12795353
TI  - Fracture resistance of endodontically treated anterior teeth restored with four
      post-and-core systems.
AB  - OBJECTIVE: The purpose of this study was to evaluate the fracture resistance and
      the mode of failure of endodontically treated teeth restored with four post-and
      core systems. METHOD AND MATERIALS: Forty intact human incisors were randomly
      divided into four groups. Teeth from each group received endodontic therapy and
      one of four post-and-core systems: serrated, parallel-sided, cast post and core;
      serrated, parallel-sided, prefabricated post and resin-composite core; carbon
      fiber-reinforced (CFC) post and resin-composite core; and ceramic post and resin
      composite core. A full-coverage metal crown was fabricated and cemented onto each
      tooth. Each specimen was subjected to a compressive load at a 45-degree angle to
      its axis until failure. The failure load was recorded and compared statistically.
      The mode of failure of the specimens was analyzed. RESULTS: There was no
      significant difference in the failure loads among groups. More catastrophic root
      fracture was detected in the group restored with ceramic posts and resin
      composite cores. CONCLUSION: The fracture resistance of endodontically treated
      teeth restored with these four post-and-core systems could be accepted
      clinically. Unfavorable tooth fracture was shown in all groups.

PMID- 12795354
TI  - Dental caries and fluorosis in low- and high-fluoride areas in Turkey.
AB  - OBJECTIVE: The aim of this study was to investigate the caries prevalence of
      children living in either low- or high-fluoride areas and to relate caries
      experience to the severity of dental fluorosis. METHOD AND MATERIALS: A total of
      278 12- to 14-year-old schoolchildren, 149 in a low-fluoride area (LFA) and 129
      in a high-fluoride area (HFA), were included in the study. The naturally
      occurring fluoride concentrations in the drinking water were 0.30 to 0.40 ppm in
      the LFA, 1.42 to 1.54 ppm in the HFA1, and 1.55 to 1.66 ppm in the HFA2. Dental
      caries was recorded with the World Health Organization criteria, and dental
      fluorosis was measured using the Tooth Surface Index of Fluorosis. RESULTS: The
      percentages of children who had an average TSIF > or = 1 were 0%, 29%, and 77% in
      the LFA, HFA1, and HFA2, respectively. The mean decayed, missing, and filled
      permanent teeth (DMFT) and decayed, missing, and filled permanent surfaces (DMFS)
      were 0.84 +/- 0.98 and 1.58 +/- 2.24 in LFA, 1.30 +/- 1.46 and 1.78 +/- 2.52 in
      HFA1, and 1.26 +/- 1.42 and 1.97 +/- 2.60 in HFA2, respectively. There was no
      significant difference in caries prevalence among children living in low- and
      high-fluoride areas when evaluated with an analysis of covariance model,
      including the frequency of toothbrushing. Toothbrushing frequency had a
      significant effect on the decayed teeth, decayed surfaces, DMFT, and DMFS. In
      high-fluoride areas, there was no relationship between caries prevalence and
      severity of fluorosis. CONCLUSION: Increasing water fluoride levels were
      associated with higher prevalence and severity of dental fluorosis and had no
      influence on caries experience in children with poor oral hygiene.

PMID- 12795355
TI  - In vitro effects of bleaching agents on FM3A cell line.
AB  - OBJECTIVE: There are concerns about the possible pathologic effects of relatively
      long-term exposure of oral tissues to bleaching agents. The purpose of the
      present study was to investigate the cytotoxic effects of various bleaching
      agents on mouse mammary carcinoma FM3A cell line. METHOD AND MATERIALS: FM3A cell
      line obtained from European Collection of Animal Cell Cultures was used in cell
      culture assay. Exponentially growing cells were seeded in 1 x 105 cells/mL in 5
      mL of RPMI 1640 medium supplemented with 10% fetal calf serum and antibiotics in
      each well of a six-well plate. PowerGel was applied onto the cell culture medium
      and incubated for 24 hours at 37 degrees C in a 5% carbon dioxide atmosphere
      after light curing. Opalescence PF gel was left on cell culture medium for 24
      hours at the same conditions. After 24-hour incubation, the cells were collected
      by trypsinization and counted with a hemocytometer. For cell viability, trypane
      blue exclusion assay was used. The cytotoxicity of PowerGel and Opalescence PF
      were determined by evaluation of cell growth and viability in comparison to
      untreated controls (cell growth = 100%). The data were submitted to statistical
      analysis (One-way analysis of variance, Dunnett's t test). RESULTS: Cell growth
      after 24 hours was significantly reduced (P = .000) in comparison to the control
      group. The cell growth in the Opalescence PF gel group also was reduced (P <
      .05). It was found that both gels affected cell viability. CONCLUSION: PowerGel
      and Opalescence PF showed a cytotoxic effect on cell growth in FM3A cell line.

PMID- 12795356
TI  - Effect of thermocycling on the retention of glass-fiber root canal posts.
AB  - OBJECTIVE: This study investigated the effects of thermocycling on the retention
      of glass-fiber and resin posts. METHOD AND MATERIALS: Forty premolar and canine
      tooth roots were embedded in acrylic blocks shaped to fit into a retention
      device. The roots were randomly assigned to two groups of 20 to receive either
      Lightposts or Luscent Anchors which were cemented into 9-mm-deep post spaces,
      with Panavia F resin cement. Each group was randomly divided into two equal
      subgroups: one for thermocycling, and the other to serve as a control. The
      thermocycled specimens were cycled 3,000 times between water baths at 5 degrees C
      and 55 degrees C, with a dwell time of 60 seconds in each. Control specimens were
      stored at 37 degrees C. The tensile force required to dislodge each post from its
      root was recorded and the data analyzed using Student's t tests. RESULTS: There
      were no significant differences in the forces required to cause post-retention
      failure between the control and thermocycled specimens. Lightposts were
      significantly more retentive than Luscent Anchors without thermocycling, but this
      distinction was not apparent in the thermocycled groups. CONCLUSION: Glass-fiber
      and resin posts cemented with resin cement offer acceptable levels of retention
      and are not susceptible to reduced retention from thermocycling. Thermocycling
      should be given less emphasis in tests for the retention of root canal posts
      cemented with resin cements.

PMID- 12795357
TI  - Study of Health in Pomerania (SHIP): a health survey in an East German region.
      Objectives and design of the oral health section.
AB  - The goal of the Study of Health in Pomerania (SHIP) was to estimate the
      prevalence of diseases, identify potential risk factors in a defined region in
      northeast Germany, and examine the particular living situation of this population
      after the reunification of East and West Germany. One of the main concerns of the
      SHIP design is the analysis of the relationships between dental, medical, social,
      and environmentally and behaviorally determined health factors. SHIP is a cross
      sectional study (clinical findings and sociologic interviews). The sample was
      drawn in two steps: Thirty-two communities in the region were selected, and
      within these communities, a simple random sample was drawn from residence
      registries, stratified by gender and age. The final sample included 4,310 males
      and females, aged 20 to 79 years. This is equivalent to a participation rate of
      68.8%. Data collection was completed in May 2001. The data collection and items
      comprised four parts: oral health examination, medical examination, health
      related interview, and a health- and risk-factor-related questionnaire. The oral
      health examination included the teeth, periodontium, oral mucosa, morphology and
      function of the craniomandibular system, and prosthodontics. The medical
      examination included blood pressure measurements; electrocardiography;
      echocardiography; carotid, thyroid, and liver ultrasound examinations; neurologic
      screening; and blood and urine sampling. The computer-assisted interview
      consisted of questions on symptoms of disease, utilization of medical and dental
      services, self-assessment of general and oral health, health behavior and
      knowledge, and socioeconomic variables. The self-administered questionnaire
      comprised housing conditions, social network, work conditions, subjective well
      being, and individual consequences of the German reunification.

PMID- 12795358
TI  - The patient with Parkinson's disease.
AB  - Parkinson's disease is an idiopathic, slowly progressive disorder of the central
      nervous system characterized by resting tremor, muscular rigidity, slow and
      decreased movement (bradykinesia), and postural instability. In the United
      States, Parkinson's disease is the fourth most common neurodegenerative disorder
      in the elderly, affecting an estimated half a million people. Oral health care
      providers can expect to be called upon to care for patients with this
      progressively debilitating disease. To provide competent care to patients with
      Parkinson's disease, clinicians must understand the disease, its treatment, and
      its impact on the patient's ability to undergo and respond to dental care.

PMID- 12795359
TI  - Ameloblastoma.

PMID- 12795360
TI  - Three-peptide control of pulsatile and entropic feedback-sensitive modes of
      growth hormone secretion: modulation by estrogen and aromatizable androgen.
AB  - The present review highlights a simplified perspective of growth hormone (GH)
      secretory control, which incorporates the individual and joint effects of final
      common signals that converge on somatotrope cells. Critical peptidyl effectors
      are GH-releasing hormone (GHRH), GH-releasing peptide (GHRP, ghrelin), and
      somatostatin. The latter three-peptide ensemble mediates stimulation, inhibition,
      and feedback suppression of GH secretion via homologous and heterologous
      interactions. Pubertal sex steroids putatively act via post-aromatized estrogen
      (e.g., testosterone converted to estradiol by aromatase) to augment sensitivity
      to GHRH, potentiate GHRP action, and mute somatostatin restraint. The dynamic
      interactions in this three-peptide network, rather than the activity of any
      single effector, subserve core adaptations in GH secretion across development.

PMID- 12795361
TI  - Near adult heights after growth hormone treatment in patients with idiopathic
      short stature or idiopathic growth hormone deficiency.
AB  - OBJECTIVE: Determination of near adult height (NAH) after recombinant human
      growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS,
      maximum stimulated growth hormone [MSGH] > 10 ng/ml) or idiopathic growth hormone
      deficiency (IGHD, MSGH < or = 10 ng/ml) enrolled in the National Cooperative
      Growth Study Substudy 2. METHODS: Female NAH was defined as height at age 18 or
      age 14 plus Tanner stage 4; male NAH was defined as height at age 20 or age 16
      plus Tanner stage 4 or 5. RESULTS: Both groups had similar enrollment heights:
      IGHD -2.7 +/- 0.7 versus ISS -2.8 +/- 0.6 (mean height standard deviation score
      [SDS] +/- SD). After rhGH treatment, there were no significant differences in NAH
      between the IGHD and ISS groups (-1.4 +/- 1.0 versus -1.6 +/- 1.0). Enrollment
      height SDS and MSGH value were significant predictors of delta height for the
      children with IGHD but not for the children with ISS (R2 = 0.45 IGHD versus R2 =
      0.22 ISS). CONCLUSION: We conclude that MSGH values should not be used as the
      primary criterion for rhGH therapy.

PMID- 12795362
TI  - An auxology-based growth hormone program: update on the Australian experience.
AB  - In 1988, new guidelines for growth hormone (GH) usage emphasizing auxological
      criteria were adopted in Australia. Currently, 1,250 children with the following
      diagnoses are being treated: idiopathic GH deficiency (IGHD), 23.4%; malignancy
      related GHD, 7.9%; Turner's syndrome, 12.1%; nonendocrine disorders, 22.2%;
      idiopathic short stature, 26.0%; endocrine disorders, 3.2%; unknown, 5.3%. At
      onset of GH therapy, mean age remained lowest in patients with IGHD (8.6 years);
      mean height SDS was unchanged over time in all groups (-2.8 to -3.3); mean GH
      doses were lowest for patients with idiopathic and malignancy-related GHD (0.15
      0.16 mg/kg/week) and highest for the Turner's syndrome group (0.22 mg/kg/week).
      Children with GHD demonstrated the best final height outcome (mean final height
      SDS -1.0 +/- 1.1 for boys and -1.4 +/- 1.2 for girls; improvements of 2.0 SDS for
      both genders). Mean final height SDS for the other etiologies were similar: -2 in
      malignancy-related GHD (no improvement), -2.3 in nonendocrine disorders
      (improvement of 0.7), -1.8 in idiopathic short stature (improvement of 1.1), and 
      2.3 for Turner's syndrome (improvement of 0.9). In 1993-94, when more stringent
      entry and exit criteria were introduced, patient numbers and expenditure were
      halved and have remained unchanged (US dollars 9-10 M per year). The use of
      auxology-based criteria continues to make possible rational, effective, and
      economical use of GH therapy in short children in Australia.

PMID- 12795363
TI  - Diagnostic growth hormone deficiency testing practices among patients in the
      NCGS/NCSS databases.
AB  - This report describes the etiology and diagnostic testing of growth hormone
      deficiency (GHD) among pediatric patients enrolled in the National Cooperative
      Growth Study (NCGS) database and adult patients enrolled in the National
      Cooperative Somatropin Surveillance (NCSS) database. The etiologies of GHD within
      the two databases are defined and compared; the various GH-stimulation tests
      utilized by participating investigators are identified; and the contribution of
      insulin-like growth factor (IGF)-I measurement to diagnostic testing is assessed.
      Throughout the report, the diagnosis and classification of patients with organic
      GHD is highlighted.

PMID- 12795364
TI  - Individualized growth hormone therapy in children: advances beyond weight-based
      dosing.
AB  - Current weight-based approaches to growth hormone (GH) dosing result in dramatic
      variability in height outcome and insulin-like growth factor (IGF) levels.
      Optimization of both safety and efficacy is desired; therefore, an intermittent,
      scheduled titration of GH to maintain serum IGF-I and IGF binding protein (IGFBP)
      3 levels within age-dependent normal ranges is physiologically sound and
      analogous to monitoring other replacement therapies used in pediatric
      endocrinology, such as in hypothyroidism. Optimal growth-promoting doses differ
      by individual, and thus surrogate markers such as IGF-I and IGFBP-3 levels are
      important in the assessment of GH treatment compliance, safety, efficacy, and
      overtreatment. With the evolution of better prediction models, a new approach
      that integrates biochemical and auxological parameters will become the standard
      of care. This approach, studied in large prospective randomized trials, will lead
      to better patient responses and fewer long-term complications.

PMID- 12795366
TI  - A practical approach to the diagnosis of growth hormone (GH) deficiency in
      patients transitioning to adulthood using GH stimulation testing.
AB  - To establish the diagnosis of adult growth hormone deficiency (GHD), GH-deficient
      children transitioning to adulthood are evaluated by two separate stimuli 2 or
      more weeks after ceasing GH therapy. While 20-88% of children diagnosed with
      idiopathic GHD retest with normal values, those with proven genetic defects in GH
      production/secretion/bioactivity and patients with panhypopituitarism
      consistently test deficient. The US Food and Drug Administration (FDA) defines
      GHD in adults by stimulated peak serum GH concentrations <5 ng/ml if measured by
      polyclonal radioimmunoassays (RIA) or lower if measured by monoclonal assays.
      Some investigators define severe GHD by a peak GH concentration <3 ng/ml. Adult
      responses to arginine and glucagon testing are similar to the responses to
      insulin tolerance testing; clonidine, pyridostigmine, and galanin cause lesser
      peaks of GH. Growth hormone-releasing hormone (GHRH) combined with arginine, GH
      releasing peptide-6 (GHRP-6), or hexarelin leads to higher peak responses than
      GHRH alone. Thus the choice of testing methods impacts the diagnosis of GHD in
      transition patients.

PMID- 12795365
TI  - Confirming the diagnosis of growth hormone deficiency (GHD) and transitioning the
      care of patients with childhood-onset GHD.
AB  - Growth hormone deficiency (GHD) diagnosed in childhood may persist into adult
      life. After attainment of final height, retesting of the patient's growth hormone
      insulin-like growth factor (GH-IGF) axis using the adult GHD diagnostic criteria
      should be performed after an appropriate interval of 1-3 months off GH therapy.
      At the time of retesting, other pituitary hormones and serum IGF-I levels should
      also be measured. The opportunity should be taken to assess body composition,
      bone mineral density, and fasting lipid and insulin levels. Patients with severe,
      long-standing, multiple pituitary hormone deficiency, genetic defects, or severe
      organic GHD can be excluded from GH retesting. When the diagnosis of adult GHD is
      established, continuation of GH therapy can be recommended unless there is a
      known risk of diabetes mellitus or malignancy. The patient's transition to GH
      replacement in adulthood should be arranged as a close collaboration between the
      pediatric and adult endocrinologists, who should discuss the reinitiation of
      treatment with the patient.

PMID- 12795367
TI  - Transition from pediatric to adult care for growth hormone deficiency.
AB  - The care of patients transitioning from adolescence to adult life always raises
      challenges for the clinician. This has proven to be especially true in the case
      of growth hormone (GH) treatment, in part due to the absence of any immediately
      observable consequences of the cessation of therapy. This paper describes the
      challenges involved in reestablishing the diagnosis of GH deficiency (GHD),
      titrating GH dosage, and sustaining patients on long-term GH treatment.

PMID- 12795369
TI  - Biochemical markers of bone metabolism: application to understanding bone
      remodeling in children and adolescents.
AB  - Markers of bone remodeling have been developed that provide biochemical indices
      that reflect changes in the rates of bone formation, resorption, and
      mineralization. These processes are important determinants of bone metabolism,
      and indicators that correspond to these processes can provide clinically relevant
      information. Until recently, the best way to measure parameters of bone
      metabolism was to perform a bone biopsy after administration of two courses of
      tetracycline. Bone markers offer significant potential advantages over bone
      biopsy. Some of these markers are protein fragments that are generated during
      metabolism of type I collagen, the major structural protein of bone, and are
      formed as this collagen is synthesized or degraded. Other markers, such as
      osteocalcin and alkaline phosphatase, are released from osteoblasts during bone
      formation. Although these markers have found significant utility in the
      evaluation of adults with metabolic bone diseases, their application in children
      has been limited due to great variability in normal ranges that reflect the
      changes in skeletal metabolism induced by age, growth rate, gender, and pubertal
      state.

PMID- 12795368
TI  - Transitioning the patient with Turner's syndrome from pediatric to adult care.
AB  - The level of medical and neuropsychological complexity throughout the life span
      of a patient with Turner's syndrome (TS) provides the rationale for a more
      structured transition from pediatric to adult health care. During late
      adolescence, the focus of care shifts from maximizing final adult height to
      completing feminization with estrogen therapy, detecting early antecedents of
      associated adult conditions, implementing needed therapeutic lifestyle changes,
      and assessing psychobehavioral risk. An increased prevalence of the dysmetabolic
      syndrome and osteoporosis is observed in TS. The prevention of obesity and
      assurance of adequate calcium intake and weight-bearing activities combined with
      early detection and treatment of specific abnormalities can ameliorate these
      associated adult morbidities. During the final phase of transition, the pediatric
      endocrinologist should engage the patient with TS in developing a comprehensive
      adult care roadmap or 'transition passport', which serves as a powerful
      educational tool. The aim of refining the transition process is to improve adult
      outcomes and quality of life for patients with TS.

PMID- 12795370
TI  - Adolescent girls, the menstrual cycle, and bone health.
AB  - In adolescent girls, amenorrhea is sometimes viewed as a variant of normal; in
      fact, however, during the first gynecologic year, the 95th percentile for cycle
      length is 90 days. Although early menstrual cycles are frequently anovulatory and
      may be somewhat irregular, girls with menses coming less frequently than every 90
      days may have significant pathology associated with hypoestrogenism.
      Hypoestrogenism is a known risk factor for the development of osteoporosis.
      Causes of oligomenorrhea and amenorrhea include the relatively common conditions
      of hyperandrogenism, eating disorders, and exercise-induced amenorrhea, as well
      as uncommon conditions such as pituitary tumor, gonadal dysgenesis, and premature
      ovarian failure. Even functional hypothalamic oligomenorrhea has been linked to
      reduced bone density. Attention to menstrual irregularity and the earlier
      diagnosis of conditions causing it may lead to interventions that will benefit
      life-long bone health.

PMID- 12795371
TI  - Juvenile osteoporosis: recognizing the risk.
AB  - Osteoporosis in children is often an undiagnosed condition. Diagnosis is usually
      made after several fractures occur with minimal trauma or radiographs demonstrate
      hypodense bones. The relationship of bone mineral density (BMD) to fracture risk
      in children is controversial. In our study, we were referred 16 patients between
      the ages of 5 and 15 years who had had two or more fractures without serious
      trauma. Dual-energy X-ray absorptiometry (DEXA) scans were performed to determine
      each patient's BMD. The mean bone density of the hip for these 16 patients
      assessed by z-score was -2.78 +/- 1.4 (SD); the mean BMD of the spine assessed by
      z-score was -3.08 +/- 1.2 (SD). Fifteen of 16 patients were osteoporotic or
      osteopenic in either the hip or the spine; 12 patients were osteoporotic in both
      the hip and the spine; one patient was osteoporotic only in the spine. These data
      strongly suggest that children with multiple fractures should be screened for
      osteoporosis.

PMID- 12795372
TI  - Selected therapy-related clinical research topics in osteoporosis.
AB  - Effective antiresorptive treatment options are currently available for fracture
      prevention in patients with osteopenia and osteoporosis. Although orally
      administered bisphosphonates are most widely used, they demonstrate specific
      compliance requirements and potential side effects. Medical therapy targeting
      acute fractures is lacking. This paper reviews two recently published studies.
      The first readdresses the use of intravenous bisphosphonates as a primary choice
      for fracture prevention; it concludes that once yearly administration may be a
      practical option. The second study assesses the effects of short-term use of a
      subcutaneous infusion of insulin-like growth factor (IGF)-I bound to its primary
      binding protein, IGFBP-3, on blunting the catabolic events associated with hip
      fractures. The investigators suggest that this intervention merits additional
      evaluation as a potentially important modality to improve care in this patient
      population.

PMID- 12795373
TI  - In spite of induced multiple defense responses, tomato plants infected with
      Cucumber mosaic virus and D satellite RNA succumb to systemic necrosis.
AB  - Cucumber mosaic virus (CMV) D satellite RNA (satRNA) attenuates the symptoms
      induced by CMV in most plants, but causes leaf epinasty and systemic necrosis in
      tomato plants, where programmed cell death (PCD) is involved. However, our
      understanding of the cellular and molecular responses to the infection of CMV D
      satRNA that result in this lethal disease remains limited. In this article, we
      show for the first time, by histochemical and molecular analysis, that multiple
      defense responses are specifically induced in CMV and D satRNA (CMV/D satRNA)
      infected tomato plants but not in mock-inoculated or CMV-infected plants. These
      responses include callose deposition and hydrogen peroxide accumulation in
      infected plants. Furthermore, the transcription of several tomato defense-related
      genes (e.g., PR-1a1, PR-1b1, PR-2, and PR-10) were activated, and the expression
      of tomato PR-5 and some abiotic and biotic stress-responsive genes (e.g.,
      catalase II and tomato analogs of Arabidopsis AtBI-1 and tobacco hsr203j) are
      enhanced. The activation and increase in expression of these genes is correlated
      with the appearance of leaf epinasty and the development of systemic necrosis in
      infected tomato plants, while increased expression of the hsr203j analog precedes
      the development of any disease symptoms. The spatial and temporal expression
      patterns of these genes as detected by RNA in situ hybridization point to the
      involvement of a complex developmental program that accompanies disease
      development resulting from CMV/D satRNA infection.

PMID- 12795374
TI  - Overexpression of a Brassica nigra cDNA gives enhanced resistance to
      Leptosphaeria maculans in B. napus.
AB  - Using a polymerase chain reaction-based strategy, we have isolated a cDNA
      sequence from Brassica nigra, denoted Lm1, which significantly improves blackleg
      resistance when expressed in transgenic oilseed rape, B. napus. Lm1 was shown to
      map to locations on linkage groups 3 and 8 in the Brassica B-genome previously
      linked to both cotyledon, adult leaf, and stem resistance. B. napus plants
      transformed with Lm1 under the control of a constitutive promoter exhibited broad
      spectrum resistance to all L. maculans isolates tested, but enhanced resistance
      to Alternaria brassicae and Verticillium longisporum was not observed. A
      transcript corresponding to the cDNA size was induced in B. nigra 12 h after
      fungal challenge from a level of weak constitutive expression previous to
      inoculation. The Lm1 sequence bears no resemblance to previously characterized
      plant resistance genes but has two predicted transmembrane motifs. Several
      sequences with high homology to Lm1 were found in the databases. Lm1 appears to
      be a member of a larger group of related genes present in a variety of plant
      species. Most of them have unknown functions, but homology between Lm1 and the
      nodule inception gene of Lotus japonicus suggests an intriguing link between
      defense-related and symbiotic pathways.

PMID- 12795375
TI  - Expression of the baculovirus p35 protein in tobacco affects cell death
      progression and compromises N gene-mediated disease resistance response to
      Tobacco mosaic virus.
AB  - The p35 protein from baculovirus is a broad-range caspase inhibitor and
      suppresses programmed cell death in animals. We report here the effects of
      transgenic expression in tobacco of the p35 protein during the hypersensitive
      response (HR). Expression of p35 causes partial inhibition of nonhost HR
      triggered by bacteria and gene-for-gene HR triggered by virus. Infection of p35
      expressing tobacco plants with Tobacco mosaic virus (TMV) disrupts N-mediated
      disease resistance, causing systemic spreading of the virus within a resistant
      background. Mutant variants altered in aspartate residues within the loop region
      of p35 are inefficient substrates for caspases in vitro, and they do not suppress
      caspase proteolytic activity in animal systems. Tobacco plants expressing these
      mutant variants of the p35 protein do not show inhibition of HR cell death or
      enhanced virus systemic movement. Thus, HR inhibition and TMV systemic spreading
      phenotype in p35-expressing plants correlate with the ability of the p35 protein
      to suppress caspase activity in animal systems. In addition, a C-terminal
      truncated variant of p35 is unable to suppress cell death in animals as well as
      HR cell death in transgenic tobacco. Our results provide evidence for the
      participation of caspase-like proteases during the HR. In addition, they suggest
      that timely activation of cell death is necessary for effective TMV containment
      within the primary infection site.

PMID- 12795376
TI  - Novel exchangeable effector loci associated with the Pseudomonas syringae hrp
      pathogenicity island: evidence for integron-like assembly from transposed gene
      cassettes.
AB  - Pseudomonas syringae strains use a type III secretion system (TTSS) to
      translocate effector proteins that assist in the parasitism of host plant cells.
      Some genes for effector proteins are clustered in the exchangeable effector locus
      (EEL) associated with the hrp pathogenicity island. A polymerase chain reaction
      based screen was developed to amplify the EEL from P. syringae strains. Of the 86
      strains screened, the EEL was successfully amplified from 30 predominately North
      American P. syringae pv. syringae strains using hrpK and queA-derived primers and
      from an additional three strains using hrpL and queA-derived primers. Among the
      amplified EEL, ten distinct types of EEL were identified that could be classified
      into six families distinguishable by genetic composition, but other types of EEL
      may be present in strains isolated in other geographical regions. No linkage with
      the host range of the source strain was apparent. Gene cassettes carrying
      conserved flanking, coding, and intergenic sequences, present in different
      combinations, were identified in the characterized EEL. Six new alleles of known
      effectors were identified that differed from the homolog in sequence, size, or
      both of the gene. One of these apparently novel effector proteins, HopPsyB,
      retained a strongly conserved amino terminus similar to that of HopPsyA, but
      other regions of the two polypeptides were only weakly similar. hopPsyB was
      expressed from an apparent operon that included hrpK and a shcA homolog, shcB.
      Escherichia coli MC4100 expressing the hrp TTSS, ShcB, and HopPsyB elicited the
      hypersensitive response (HR) in tobacco, consistent with effector production.
      Indicative of translocation as an effector, P. syringae pv. tomato DC3000
      expressing a HopPsyB':'AvrRpt2 fusion elicited the HR in RPS2+ Arabidopsis
      thaliana. P. syringae pv. tomato DC3000 carrying HopPsyB exhibited slightly
      enhanced virulence in several Brassica spp. These results are consistent with the
      hypotheses that the EEL is a source of disparate effectors functioning in
      pathogenicity of P. syringae strains and that it evolved independently of the hrp
      pathogenicity island central conserved region, most likely through integron-like
      assembly of transposed gene cassettes.

PMID- 12795377
TI  - A global analysis of protein expression profiles in Sinorhizobium meliloti:
      discovery of new genes for nodule occupancy and stress adaptation.
AB  - A proteomic examination of Sinorhizobium meliloti strain 1021 was undertaken
      using a combination of 2-D gel electrophoresis, peptide mass fingerprinting, and
      bioinformatics. Our goal was to identify (i) putative symbiosis- or nutrient
      stress-specific proteins, (ii) the biochemical pathways active under different
      conditions, (iii) potential new genes, and (iv) the extent of posttranslational
      modifications of S. meliloti proteins. In total, we identified the protein
      products of 810 genes (13.1% of the genome's coding capacity). The 810 genes
      generated 1,180 gene products, with chromosomal genes accounting for 78% of the
      gene products identified (18.8% of the chromosome's coding capacity). The
      activity of 53 metabolic pathways was inferred from bioinformatic analysis of
      proteins with assigned Enzyme Commission numbers. Of the remaining proteins that
      did not encode enzymes, ABC-type transporters composed 12.7% and regulatory
      proteins 3.4% of the total. Proteins with up to seven transmembrane domains were
      identified in membrane preparations. A total of 27 putative nodule-specific
      proteins and 35 nutrient-stress-specific proteins were identified and used as a
      basis to define genes and describe processes occurring in S. meliloti cells in
      nodules and under stress. Several nodule proteins from the plant host were
      present in the nodule bacteria preparations. We also identified seven potentially
      novel proteins not predicted from the DNA sequence. Post-translational
      modifications such as N-terminal processing could be inferred from the data. The
      posttranslational addition of UMP to the key regulator of nitrogen metabolism,
      PII, was demonstrated. This work demonstrates the utility of combining mass
      spectrometry with protein arraying or separation techniques to identify candidate
      genes involved in important biological processes and niche occupations that may
      be intransigent to other methods of gene expression profiling.

PMID- 12795378
TI  - Phylogeny of HCN synthase-encoding hcnBC genes in biocontrol fluorescent
      pseudomonads and its relationship with host plant species and HCN synthesis
      ability.
AB  - Hydrogen cyanide (HCN) is a broad-spectrum antimicrobial compound involved in
      biological control of root diseases by many plant-associated fluorescent
      pseudomonads. The HCN synthase is encoded by three biosynthetic genes (hcnA,
      hcnB, and hcnC), but little is known about the diversity of these genes in
      fluorescent Pseudomonas spp. and in other bacteria. Here, the partial hcnBC
      sequence was determined for a worldwide collection of biocontrol fluorescent
      Pseudomonas spp. Phylogenies based on hcnBC and deduced protein sequences
      revealed four main bacterial groups, but topological incongruences were found
      between hcnBC and rrs-based phylogenies, suggesting past lateral transfer of
      hcnBC among saprophytic root-colonizing pseudomonads. Three of the four groups
      included isolates from different countries and host plants. Yet, these groups
      corresponded to distinct, ecologically-adapted populations of HCN-producing
      biocontrol fluorescent pseudomonads, as indicated by high hcnBC distinctness
      ratio values and the differences in production levels of HCN in vitro found
      between groups. This is in accordance with previous results on catabolic
      properties and biocontrol abilities of these strains. HCN synthase gene diversity
      may thus reflect the adaptive radiation of HCN+ biocontrol fluorescent
      pseudomonads. Positive correlations were found between HCN production in vitro
      and plant protection in the cucumber/Pythium ultimum and tomato/Fusarium
      oxysporum f. sp. radicis-lycopersici pathosystems.

PMID- 12795379
TI  - Characterization of a Ralstonia solanacearum operon required for
      polygalacturonate degradation and uptake of galacturonic acid.
AB  - The bacterial wilt pathogen Ralstonia solanacearum produces three extracellular
      polygalacturonases (PGs): PehA, PehB, and PehC. All three PGs hydrolyze pectin's
      polygalacturonic acid backbone, but each releases different reaction products.
      PehA and PehB contribute significantly to pathogen virulence, probably by
      facilitating root invasion and colonization. To determine the collective
      contribution of PGs to virulence and saprophytic survival, we cloned,
      characterized, and mutated the R. solanacearum pehC gene, which encodes a
      distinctive monogalacturonate-releasing exo-PG. The virulence of a pehC mutant on
      tomato was indistinguishable from that of its wild-type parent; thus, this exo-PG
      alone does not contribute significantly to wilt pathogenesis. Unexpectedly, a
      completely PG-deficient triple pehA/B/C mutant was slightly more virulent than a
      pehA/B mutant. PehC may degrade galacturonide elicitors of host defense, thereby
      protecting the pathogen from plant antimicrobial responses. A galacturonate
      transporter gene, exuT, is immediately downstream of pehC and the two genes are
      co-transcribed. It has been hypothesized that galacturonic acid released by PGs
      from plant cell walls nourishes bacteria during pathogenesis. To separate the
      pectolytic and nutrient-generating roles of the PGs, we made an exuT mutant,
      which still produces all three isozymes of PG but cannot uptake PG degradation
      products. This exuT mutant had wild-type virulence on tomato, demonstrating that
      metabolism of galacturonic acid does not contribute significantly to bacterial
      success inside the plant.

PMID- 12795380
TI  - Molecular evidence that the extracellular cutinase Pbc1 is required for
      pathogenicity of Pyrenopeziza brassicae on oilseed rape.
AB  - Recent evidence has suggested that cutinase is required for cuticular penetration
      and, therefore, is essential for pathogenicity of Pyrenopeziza brassicae, the
      causal organism of light leaf spot disease of oilseed rape and other brassicas.
      In order to acquire molecular evidence for the role of cutinase in pathogenesis,
      the single-copy P. brassicae cutinase gene Pbc1 was disrupted by a transformation
      mediated approach. Southern hybridization analysis revealed that in one mutant,
      NH10-1224, the disruption was due to a tandem insertion of two copies of the
      disruption vector into the 5' coding region of Pbc1. In contrast to the wild
      type, no expression of Pbc1 was detected during in planta growth or in cutin
      induced mycelium of NH10-1224 and no cutinase activity was detected in culture
      supernatants from NH10-1224 using p-nitrophenyl butyrate as substrate. Scanning
      electron microscopy of Brassica napus cotyledons infected with wild-type P.
      brassicae confirmed that entry into the host is by direct penetration of the
      cuticle. In contrast, the cutinase-deficient mutant NH10-1224 failed to penetrate
      the cuticular layer and was unable to develop disease symptoms. This evidence is
      consistent with the hypothesis that Pbc1 is required for P. brassicae to
      penetrate the plant cuticle. Demonstration that complementation of NH10-1224 with
      the Pbc1 wild-type gene restores both cutinase activity and pathogenicity will be
      required to definitively establish that cutinase is required for successful
      pathogenesis of brassicas by P. brassicae.

PMID- 12795381
TI  - The endopolygalacturonase 1 from Botrytis cinerea activates grapevine defense
      reactions unrelated to its enzymatic activity.
AB  - A purified glycoprotein from Botrytis cinerea (strain T4), identified as
      endopolygalacturonase 1 (T4BcPG1) by mass spectrometry analysis, has been shown
      to activate defense reactions in grapevine (Vitis vinifera cv. Gamay). These
      reactions include calcium influx, production of active oxygen species, activation
      of two mitogen-activated protein kinases, defense gene transcript accumulation,
      and phytoalexin production. Most of these defense reactions were also activated
      in grapevine in response to purified oligogalacturonides (OGA) with a degree of
      polymerization of 9 to 20. In vivo, these active OGA might be a part of the
      released products resulting from endopolygalacturonase activity on plant cell
      walls. Nevertheless, the intensity and kinetics of events triggered by OGA were
      very different when compared with T4BcPG1 effects. Moreover, chemical treatments
      of T4BcPG1 and desensitization assays have allowed us to discriminate enzymatic
      and elicitor activities, indicating that elicitor activity was not due to
      released oligogalacturonides. Thus, BcPG1 should be considered as both an
      avirulence and a virulence factor. The role of the secreted BcPG1 in the
      pathogenicity of Botrytis cinerea is discussed.

PMID- 12795382
TI  - Conceptions of moral, social-conventional, and personal events among Chinese
      preschoolers in Hong Kong.
AB  - Sixty-one Chinese preschoolers from Hong Kong at 2 ages (Ms = 4.36 and 6.00
      years) were interviewed about familiar moral, social-conventional, and personal
      events. Children treated personal events as distinct from moral obligations and
      conventional regulations. Children judged the child as deciding personal issues,
      based on personal choice justifications, whereas children judged parents as
      deciding moral and conventional issues. With age, children granted increased
      decision-making power to the child. In contrast, children viewed moral
      transgressions as more serious, generalizably wrong, and wrong independent of
      authority than other events, based on welfare and fairness. Punishment-avoidance
      justifications for conventional events decreased with age, whereas conventional
      justifications increased. Young Chinese preschool children make increasingly
      differentiated judgments about their social world.

PMID- 12795383
TI  - Overt and covert verbal problem-solving strategies: developmental trends in use,
      awareness, and relations with task performance in children aged 5 to 17.
AB  - Age-related changes in children's use, self report, and awareness of verbal
      problem-solving strategies (private speech) and strategy effectiveness were
      explored with a large (N = 2,156) cross-sectional sample of children aged 5 to
      17. Children's verbal strategies moved from overt, to partially covert, to fully
      covert forms with age. Self-reports of verbal strategy use were accurate yet
      incomplete. Awareness of children's use of verbal strategies was low and
      increased with age. Although verbal strategies were associated with competence
      among the youngest children, self-talk was unrelated to task performance for
      older children, suggesting considerable persistence over time of a relatively
      ineffective strategy. Awareness was not a prerequisite for children's verbal
      strategy use but was positively associated with strategy effectiveness among
      those who talked.

PMID- 12795384
TI  - Six-month-old infants' categorization of containment spatial relations.
AB  - Six-month-old infants' ability to form an abstract category of containment was
      examined using a standard infant categorization task. Infants were habituated to
      4 pairs of objects in a containment relation. Following habituation, infants were
      tested with a novel example of the familiar containment relation and an example
      of an unfamiliar relation. Results indicate that infants look reliably longer at
      the unfamiliar versus familiar relation, indicating that they can form a
      categorical representation of containment. A second experiment demonstrated that
      infants do not rely on object occlusion to discriminate containment from a
      support or a behind spatial relation. Together, the results indicate that by 6
      months, infants can recognize a containment relation from different angles and
      across different pairs of objects.

PMID- 12795385
TI  - Continuity and change in levels of externalizing behavior in school of children
      from economically disadvantaged families.
AB  - This study used a person-centered approach to understand continuity and change in
      the externalizing behavior of children from economically disadvantaged families
      (N = 134). Groups of children differed in showing high levels of externalizing
      behavior in first grade (7 years old) that persisted (persistent problem) or
      decreased (improver) in third grade (9 years old) and low levels in first grade
      that were stable (unproblematic) or increased (new problem) in third grade. The
      results showed that verbal ability, behavioral impulsivity, parent maladjustment,
      and harsh parenting distinguished the persistent problem and unproblematic
      groups. Family instability was associated with change for the improver and new
      problem groups. The results suggest the importance of examining changes in the
      early adjustment to school for children from economically disadvantaged families.

PMID- 12795386
TI  - The peer group as a context: mediating and moderating effects on relations
      between academic achievement and social functioning in Chinese children.
AB  - The purpose of the study was to examine, in a large sample of Chinese children
      and adolescents at 9, 13, and 16 years of age, the contextual effects of the peer
      group on relations between academic achievement and social functioning. Data on
      informal peer groups, social functioning and academic achievement were collected
      from multiple sources. It was found that peer groups were highly homogenous on
      academic achievement. Hierarchical linear modeling analysis revealed that
      academic achievement and social adjustment were associated at both the within
      group individual level and the group level. Moreover, group academic performance
      moderated the relations between academic achievement and social adjustment such
      as peer acceptance, social competence, and leadership, suggesting that individual
      level relations might be enhanced or exacerbated by group academic norms.

PMID- 12795387
TI  - Reducing misinformation effects in children with cognitive interviews:
      dissociating recollection and familiarity.
AB  - Two experiments examined the effect of a cognitive interview on 4- and 8-year-old
      children's correct recall and subsequent reporting of misinformation. Children
      viewed an event followed by misinformation that was read or self-generated either
      before or after a cognitive interview. Children were then given a recognition
      test under inclusion and exclusion instructions. A cognitive interview elicited
      more correct details than a control interview. Age-related changes were found
      such that the 8-year-old children's reports were more complete and they recalled
      more correct person, action, object, and location details than the 4-year-old
      children. A cognitive interview given after postevent misinformation reduced
      children's reporting of misinformation at interview and reduced reporting of self
      generated misinformation at test. Process dissociation analyses revealed that
      recollection increased but familiarity decreased with age.

PMID- 12795388
TI  - Parents' monitoring-relevant knowledge and adolescents' delinquent behavior:
      evidence of correlated developmental changes and reciprocal influences.
AB  - Links between parental knowledge and adolescent delinquent behavior were tested
      for correlated rates of developmental change and reciprocal associations. For 4
      years beginning at age 14, adolescents (N = 396) reported on their delinquent
      behavior and on their parents' knowledge of their whereabouts and activities.
      Parents completed measures of their adolescents' delinquent behavior. Knowledge
      was negatively correlated with delinquent behaviors at baseline, and increases
      over time in knowledge were negatively correlated with increases in parent
      reported delinquent behavior. Reciprocal associations indicate that low levels of
      parental knowledge predict increases in delinquent behavior and that high levels
      of delinquent behavior predict decreases in knowledge. Discussion considers both
      youth-driven and parent-driven processes that may account for the correlated
      developmental changes and reciprocal associations.

PMID- 12795389
TI  - Role of affective self-regulatory efficacy in diverse spheres of psychosocial
      functioning.
AB  - This prospective study with 464 older adolescents (14 to 19 years at Time 1; 16
      to 21 years at Time 2) tested the structural paths of influence through which
      perceived self-efficacy for affect regulation operates in concert with perceived
      behavioral efficacy in governing diverse spheres of psychosocial functioning.
      Self-efficacy to regulate positive and negative affect is accompanied by high
      efficacy to manage one's academic development, to resist social pressures for
      antisocial activities, and to engage oneself with empathy in others' emotional
      experiences. Perceived self-efficacy for affect regulation essentially operated
      mediationally through the latter behavioral forms of self-efficacy rather than
      directly on prosocial behavior, delinquent conduct, and depression. Perceived
      empathic self-efficacy functioned as a generalized contributor to psychosocial
      functioning. It was accompanied by prosocial behavior and low involvement in
      delinquency but increased vulnerability to depression in adolescent females.

PMID- 12795390
TI  - Chinese adolescents' reasoning about democratic and authority-based decision
      making in peer, family, and school contexts.
AB  - This study explored the judgments and reasoning of Chinese adolescents (13-18
      years of age) from 3 regions of mainland China (N = 574) regarding procedures for
      making decisions involving children in peer, family, and school contexts.
      Participants evaluated 2 democratic decision-making procedures (majority rule and
      consensus) and decision making by adult authorities for 2 decisions embedded in
      each social context. Judgments and reasoning about decision-making procedures
      varied by social context and by the decision under consideration, and evaluations
      of procedures became more differentiated with increasing age. The findings reveal
      that concepts of rights, individual autonomy, and democratic norms (majority
      rule) are salient aspects of Chinese adolescents' social reasoning and are used
      to evaluate critically existing social practices.

PMID- 12795392
TI  - Is a picture worth a thousand words? Preference for auditory modality in young
      children.
AB  - Linguistic labels play an important role in young children's conceptual
      organization: When 2 entities share a label, people expect these entities to
      share many other properties. Two classes of explanations of the importance of
      labels seem plausible: a language-specific and a general auditory explanation.
      The general auditory explanation argues that the importance of labels stems from
      a privileged processing status of auditory input (as compared with visual input)
      for young children. This hypothesis was tested and supported in 4 experiments.
      When auditory and visual stimuli were presented separately, 4-year-olds were
      likely to process both kinds of stimuli, whereas when auditory and visual stimuli
      were presented simultaneously, 4-year-olds were more likely to process auditory
      stimuli than visual stimuli.

PMID- 12795391
TI  - Does father absence place daughters at special risk for early sexual activity and
      teenage pregnancy?
AB  - The impact of father absence on early sexual activity and teenage pregnancy was
      investigated in longitudinal studies in the United States (N = 242) and New
      Zealand (N = 520), in which community samples of girls were followed
      prospectively from early in life (5 years) to approximately age 18. Greater
      exposure to father absence was strongly associated with elevated risk for early
      sexual activity and adolescent pregnancy. This elevated risk was either not
      explained (in the US. study) or only partly explained (in the New Zealand study)
      by familial, ecological, and personal disadvantages associated with father
      absence. After controlling for covariates, there was stronger and more consistent
      evidence of effects of father absence on early sexual activity and teenage
      pregnancy than on other behavioral or mental health problems or academic
      achievement. Effects of father absence are discussed in terms of life-course
      adversity, evolutionary psychology, social learning, and behavior genetic models.

PMID- 12795393
TI  - A longitudinal study of mathematical competencies in children with specific
      mathematics difficulties versus children with comorbid mathematics and reading
      difficulties.
AB  - Mathematical competencies of 180 children were examined at 4 points between 2nd
      and 3rd grades (age range between 7 and 9 years). Children were initially
      classified into one of 4 groups: math difficulties but normal reading (MD only),
      math and reading difficulties (MD-RD), reading difficulties but normal math (RD
      only), and normal achievement in math and reading (NA). The groups did not differ
      significantly in rate of development. However, at the end of 3rd grade the MD
      only group performed better than the MD-RD group in problem solving but not in
      calculation. The NA and RD only groups performed better than the MD-RD group in
      most areas. Deficiencies in fact mastery and calculation fluency, in particular,
      are defining features of MD, with or without RD.

PMID- 12795394
TI  - The effects of a time-limited welfare program on children: the moderating role of
      parents' risk of welfare dependency.
AB  - This study examined the effect of a time-limited welfare program on school-age
      children using data on almost 3,000 children (ages 5-17 at the four year follow
      up-point) from the random assignment evaluation of Florida's Family Transition
      Program (FTP). FTP was one of the first welfare reform initiatives to impose a
      time limit on the receipt of cash assistance, and it combined the time limit with
      a rich array of mandatory services. The effects of FTP on children were moderated
      by families' risk of long-term welfare dependency. Contrary to predictions laid
      out at the outset, there were few effects of FTP on middle childhood and
      adolescent children for children of parents most likely to be long-term welfare
      dependent (those most likely to hit the time limit). However, consistent negative
      effects on this same age group of children were found for children of parents
      least likely to be long-term welfare dependent--parents who had the largest
      employment gains--and effects of FTP were most strongly negative for the oldest
      adolescent children. The findings suggest a different theoretical model for
      movements into employment than the one suggested in the previous literature for
      job loss. The findings are discussed in terms of their contribution to research
      and policy.

PMID- 12795395
TI  - The relations of parenting, effortful control, and ego control to children's
      emotional expressivity.
AB  - The relations of observed parental warmth and positive expressivity and
      children's effortful control and ego control with children's high versus low
      emotional expressivity were examined in a 2-wave study of 180 children (M age =
      112.8 months). There were quadratic relations between adults' reports of
      children's emotional expressivity and effortful control; moderate expressivity
      was associated with high effortful control. Structural equation models supported
      the hypothesis that children's ego overcontrol (versus undercontrol) mediated the
      relation between parental warmth or positive expressivity and children's
      emotional expressivity, although parenting at the follow-up did not uniquely
      predict in children's expressivity after controlling for the relations in these
      constructs over time. The alternative hypothesis that children's ego overcontrol
      elicited positive parenting and expressivity also was supported.

PMID- 12795396
TI  - Early representational insight: twenty-four-month-olds can use a photo to find an
      object in the world.
AB  - The research reported here shows that under certain circumstances even 24-month
      old children can display representational insight. Seventy-nine children
      participated in 3 studies in which a photo or video presentation could be used to
      guide their search for a hidden object. Studies 1 and 2 replicated earlier
      findings of chance performance levels across 4 trials. However, on their first
      trial, 24-month-olds performed above chance in 3 of 4 conditions in these
      experiments. Study 3 therefore presented children not with the typical 4 trials
      in 1 room, but with 1 trial each in 4 different rooms. This manipulation ruled
      out perseveration errors and resulted in above-chance performance in average mean
      retrieval rates. These results call for first-trial reanalyses of earlier
      studies.

PMID- 12795397
TI  - A longitudinal investigation of the dynamics of mental state talk in families.
AB  - Thirty-seven mothers and fathers were observed in their homes interacting with
      their 2- and 4-year-old-children at Time 1 and 2 years later. Parental mental
      state talk to children varied as a function of children's age, the context in
      which talk occurred, and the gender of the parent. Four-year-old children, with
      an older sibling, produced and heard more cognitive talk and less desire talk
      than children without an older sibling. Cognitive and feeling talk by family
      members at Time 1 predicted change in younger children's cognitive and feeling
      talk (respectively) 2 years later, after controlling for initial levels of
      younger children's talk and general language ability. Findings are discussed in
      the context of theory of mind understanding and family talk about the mind.

PMID- 12795398
TI  - Young children's play qualities in same-, other-, and mixed-sex peer groups.
AB  - This research examined how children's play varied as a function of the sex of the
      child, the sex of the play partner, and whether they played in dyads or groups.
      Children (mean age = 52 months) were observed during their free play. Data
      revealed that boys' same-sex play was more active-forceful, further from adults,
      and more stereotyped than girls' play, and that this pattern was generally
      exaggerated in groups versus dyads. Children rarely played only with children of
      the other sex (other-sex peers), but about one fourth of their interactions
      involved children of both sexes (mixed-sex peers). Compared with same- or dyadic
      other-sex play, mixed-sex play was more likely to occur near adults, and was
      intermediate in active-forceful and stereotyped activity choices. Findings
      confirmed that children's experiences in peer groups vary depending on the sex of
      the child and sex of play partners.

PMID- 12795399
TI  - Nonshared environmental influences on individual differences in early behavioral
      development: a monozygotic twin differences study.
AB  - The monozygotic (MZ) twin differences method was used to investigate nonshared
      environmental (NSE) influences independent of genetics. Four-year-old MZ twin
      pairs (N = 2,353) were assessed by their parents on 2 parenting measures (harsh
      parental discipline and negative parental feelings) and 4 behavioral measures
      (anxiety, prosocial behavior, hyperactivity, and conduct problems). Within-pair
      differences in parenting correlated significantly with MZ differences in
      behavior, with an average effect size of 3%. For the extreme 10% of the parenting
      discordant and behavior-discordant distributions, the average NSE effect size was
      substantially greater (11%), suggesting a stronger NSE relationship for more
      discordant twins. NSE relationships were also stronger in higher risk
      environments, that is, families with lower socioeconomic status, greater family
      chaos, or greater maternal depression.

PMID- 12795400
TI  - Children's perseverative appearance-reality errors are related to emerging
      language skills.
AB  - Two experiments explored the communicative bases of preschoolers' object
      appearance-reality (AR) errors. In Experiment 1, 3-, 4-, and 5-year-olds (N = 36)
      completed the AR test (with high- and low-deceptive objects), a control test with
      the same discourse structure but nondeceptive stimuli, and stimulus naming and
      memory tests. AR performance correlated positively with control (discourse) and
      naming test performance. Object deceptiveness had little effect. In Experiment 2,
      3- and 4-year-olds (N = 64) completed AR tests that experimentally varied
      question phrasing and use of exemplar objects. Children also completed memory,
      vocabulary, and control tests (of verbal perseveration). AR performance variance
      was predicted by a composite perseveration score from three non-AR tasks,
      vocabulary, and exemplars. The results indicate that the discourse structure of
      the AR test elicits a perseverative tendency that is mediated by children's
      verbal knowledge.

PMID- 12795401
TI  - ORF98 of Autographa californica nucleopolyhedrosisvirus is an auxiliary factor in
      late gene expression.
AB  - Autographa californica nucleopolyhedrosisvirus (AcMNPV) is the type member of the
      family Baculoviridae. Gene expression of AcMNPV during virus infection is
      temporally regulated. A series of late expression factors (LEFs) are required for
      late gene expression to take place. A number of additional factors have also been
      shown to more modestly influence late gene expression. Using the LEF transient
      assay, we scanned the AcMNPV genome for such factors by replacing plasmids using
      the LEF genes with larger clones and then looked for increases in late gene
      expression using a reporter plasmid under the control of a late promoter. Using
      this approach, ORF98 was identified as having a stimulatory effect on late gene
      expression. The ability of ORF98 to influence early, late, and very late gene
      expression was established. Furthermore, tagged versions of ORF98 were localized
      to the nuclei of transfected cells and were shown to interact with each other as
      homo-oligomers. Potential roles of ORF98 in baculovirus infection are discussed.

PMID- 12795402
TI  - Interaction of secretory immunoglobulin A antibodies with Naegleria fowleri
      trophozoites and collagen type I.
AB  - In this work, we analyzed the in vitro interaction of human secretory
      immunoglobulin A (sIgA) antibodies with Naegleria fowleri trophozoites and the
      capacity of these antibodies to inhibit amoeba adherence to collagen type I. We
      also studied N. fowleri antigens that are recognized by sIgA, using immunoblot
      assays. Immunocytochemical analysis of the interaction showed a redistribution of
      antigens on the surface of trophozoites by sIgA antibodies. Ultrastructural
      analysis of antibody-amoeba interaction showed that besides the patching and cap
      formation, parasites were capable of eliminating the antigen-antibody complex
      produced on the surface. sIgA antibodies were capable of inhibiting the in vitro
      adhesion of trophozoites to collagen type I. We suggest that nonsymptomatic
      infections by N. fowleri may stimulate a local specific immunity that prevents
      trophozoite adhesion and invasion of nasal mucosa.

PMID- 12795403
TI  - Characteristics of a cluster of xylanase genes in Fibrobacter succinogenes S85.
AB  - Xylanase genes xyn10D, xyn10E, and xyn10B, located sequentially on the
      Fibrobacter succinogenes S85 chromosome, were separately cloned and their
      properties characterized. Analysis of the sequences documented that xylanases
      Xyn10D, Xyn10E, and Xyn10B each consist of an N-terminal catalytic domain
      (glycosyl hydrolase family 10) and a C-terminal carbohydrate-binding module (CBM,
      family 6) connected by proline-rich linker sequences. The amino acid sequences
      exhibited similarities of between 53 and 60%. The xyn10D, xyn10E, and truncated
      xyn10deltaACBM were expressed in Escherichia coli and purified to homogeneity.
      The purified Xyn10D, Xyn10E, and Xyn10BdeltaCBM exhibited the same temperature
      optimum (40 degrees C) and pH optimum (6.5) and the highest specific activity
      against arabinoxylan, oat spelt xylan, and birchwood xylan, respectively. Xyn10D
      exhibited an affinity for cellulose and xylan with 47 and 33% binding,
      respectively, while the truncated Xyn10DdeltaCBM did not bind to the substrates.
      The main hydrolysis products of the three xylanases acting on oat spelt xylan and
      arabinoxylan were xylose and xylobiose. RT-PCR analysis showed that the three
      genes were co-transcribed as a single transcript. Western immunoblot analysis
      revealed that the three xylanases were expressed at a very low level by F.
      succinogenes grown on either glucose or cellulose as the source of carbohydrate.

PMID- 12795404
TI  - Biodegradation of cyclic amines by a Pseudomonas strain involves an amine mono
      oxygenase.
AB  - Pseudomonas putida O1G3 catalyzes the degradation of pyrrolidine and piperidine.
      This strain can use these compounds as the sole source of carbon, nitrogen, and
      energy. When the cyclic amines were used as the growth substrates, the synthesis
      of a soluble heme amine mono-oxygenase was induced in this bacteria. This
      observation was confirmed by spectrophotometric analysis and specific inhibitor.
      This mono-oxygenase is a NADH-dependent enzyme and catalyzes the cleavage of the
      C-N bond of the pyrrolidine and piperidine ring by a mechanism similar to a N
      dealkylation. This reaction could be followed by ring cleavage to form gamma
      aminobutyraldehyde oxidized to gamma-aminobutyrate. Further investigations to
      purify the heme-containing mono-oxygenase are in progress.

PMID- 12795405
TI  - Immunodetection of spectrin-like proteins in yeasts.
AB  - Spectrin, a component of the membrane skeleton in erythrocytes and other animal
      cells, has also been identified in plant and fungal cells. However, its
      postulated role, i.e., the maintenance of shape and elasticity of the plasma
      membrane, is probably not exerted in walled cells. To study spectrin in these
      cells, we chose yeasts because of a high morphological variability of their life
      cycle. The localization of spectrin in the cells and protoplasts of Saccharomyces
      cerevisiae and Schizosaccharomyces japonicus var. versatilis was detected by
      immunoblotting, indirect immunofluorescence, and immunogold electron microscopy
      techniques with the use of anti-chicken and anti-human erythrocyte spectrin
      antibodies. A protein band of 220-240 kDa and some bands of lower relative mass
      were detected in cell and protoplast extracts of both yeast strains. Spectrin
      like proteins were revealed by fluorescence microscopy at cell surfaces and in
      vacuolar membranes. Immunogold-labelling showed spectrin-like proteins in the
      plasma membrane, endoplasmic reticulum, vacuoles, nuclei, vesicles, mitochondria,
      and cell walls. The topology of spectrin was not affected by actin
      depolymerization with Latrunculin B nor was it changed in either act1-1 or cdc42
      mutants, under restrictive conditions. Under osmotic stress, both spectrin and
      actin were delocalized and appeared in the form of large clusters in the
      cytoplasm. It is concluded that a protein cross-reacting with spectrin antibodies
      is present in fission and budding yeasts. Generally, it is located in the
      proximity of the plasma membrane and other intracellular membranes, probably as a
      part of the membrane skeleton. No evidence of its relationship to either actin or
      growth zones of the cell can be provided.

PMID- 12795406
TI  - Nitrate reductase from the magnetotactic bacterium Magnetospirillum
      magnetotacticum MS-1: purification and sequence analyses.
AB  - We purified the nitrate reductase from the soluble fraction of Magnetospirillum
      magnetotacticum MS-1. The enzyme was composed of 86- and 17-kDa subunits and
      contained molybdenum, non-heme iron, and heme c. These properties are very
      similar to those of the periplasmic nitrate reductase found in Paracoccus
      pantotrophus. The M. magnetotacticum nap locus was clustered in seven open
      reading frames, napFDAGHBC. The phylogenetic analyses of NapA, NapB, and NapC
      suggested a close relationship between M. magnetotacticum nap genes and
      Escherichia coli nap genes, which is not consistent with the 16S rDNA data. This
      is the first finding that the alpha subclass of Proteobacteria possesses a
      napFDAGHBC-type nap gene cluster. The nap gene cluster had putative fumarate and
      nitrate reduction regulatory protein (Fnr) and NarL protein binding sites.
      Furthermore, we investigated the effect of molybdate deficiency in medium on the
      total iron content of the magnetosome fraction and discussed the physiological
      function of nitrate reductase in relation to the magnetite synthesis in M.
      magnetotacticum.

PMID- 12795407
TI  - Group 1 beta-lactamases of Aeromonas caviae and their resistance to beta-lactam
      antibiotics.
AB  - The contribution of beta-lactamase production to beta-lactam antibiotic
      resistance was examined in an Aeromonas caviae mutant strain, selected in vitro
      by cefotaxime and derived from a wild-type strain isolated in our laboratory from
      crude sewage. Both strains produced beta-lactamase. The mutant strain (AC7m)
      produced beta-lactamase constitutively, in contrast to the parental strain (AC7),
      which was inducible by cefoxitin. AC7m was regarded as a mutant from AC7, which
      over-expressed beta-lactamase. The mutant strain showed a remarkable reduction in
      sensitivity to most of the beta-lactam antibiotics tested, such as (i)
      aminopenicillins and their combinations with clavulanic acid and sulbactam, (ii)
      carboxypenicillins, (iii) ureidopenicillins, and (iv) cephalosporins. This strain
      remained susceptible to ceftazidime, imipenem, and aztreonam. Isoelectric
      focusing of sonic extracts revealed that both strains AC7 and AC7m shared a
      common major beta-lactamase band at pI 6.5. The plasmid DNA assays showed that
      the beta-lactamases expressed by each A. caviae strain were chromosomally
      encoded. Based on substrate and inhibitor profiles determined in sonic extracts
      for AC7 and AC7m, the enzymes displayed on isoelectric focusing at pI 6.5 were
      assigned to chromosomal Group 1 beta-lactamases. Imipenem would therefore be the
      appropriate choice for therapy of infections caused by A. caviae beta-lactamase
      over-expressing mutants.

PMID- 12795408
TI  - Stimulation of the cyanide-resistant alternative respiratory pathway by oxygen in
      Acremonium chrysogenum correlates with the size of the intracellular peroxide
      pool.
AB  - The relationship between oxygen input and activity of the cyanide-resistant
      alternative respiration of submerged cultures of Acremonium crysogenum was
      investigated. The volumetric oxygen transfer coefficient of the respective
      cultures correlated positively within almost two ranges of magnitude with the
      size of the intracellular peroxide pool, which in turn, correlated with the
      activity of the cyanide-resistant alternative respiratory pathway. Increased
      aeration also stimulated the glucose uptake rate but had no effect on the total
      respiration rate or the growth rate. Addition of the lipid peroxyl radical
      scavenger DL-alpha-tocopherol to A. chrysogenum cultures decreased the rate of
      intracellular peroxide production as well as glucose uptake. An increase in the
      cyanide-resistant fraction of total respiration was observed, while growth and
      the total respiratory activity remained unchanged. We conclude that intracellular
      peroxides may stimulate the alternative respiration in A. chrysogenum.

PMID- 12795409
TI  - Extracellular metalloproteinases in Phytomonas serpens.
AB  - The detection of extracellular proteinases in Phytomonas serpens, a
      trypanosomatid isolated from tomato fruits, is demonstrated in this paper.
      Maximal production occurred at the end of the logarithmic phase of growth. These
      enzymes exhibited selective substrate utilization in SDS-PAGE, being more active
      with gelatin; hemoglobin and bovine serum albumin were not degraded. Three
      proteinases were detected in SDS-PAGE-gelatin, with apparent molecular masses
      between 94 and 70 kDa. The proteolytic activity was completely blocked by 1,10
      phenanthroline and strongly inhibited by EDTA, whereas a partial inhibition was
      observed with trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64) and
      soybean trypsin inhibitor; phenylmethylsulfonyl fluoride weakly inhibited the
      enzymes. This inhibition profile indicated that these extracellular proteinases
      belong to the metalloproteinase class.

PMID- 12795410
TI  - Bacteriophage lambda repressor allelic modulation of the Rex exclusion phenotype.
AB  - The sensitivity of delta red-gam delta ren mutants of bacteriophage lambda to Rex
      exclusion by lambda rexA+ rexB+ lysogens is modulated by the prophage cI
      repressor allele. We show the following: (i) lambda spi156 delta nin5 forms
      plaques on a cI+-rexA+-rexB+ lysogen with 10(5)-fold higher efficiency than on
      cI[Ts]-rexA+-rexB+ derivatives. (ii) The cI[Ts]857 allele augmentation of Rex
      exclusion is recessive to cI+. (iii) The cI857-mediated increase in Rex exclusion
      activity involves the participation of a genetic element mapping outside of cI
      rexA-rexB.

PMID- 12795411
TI  - Blocking of Pseudomonas aeruginosa lectins by human milk glycans.
AB  - The opportunistic human pathogen Pseudomonas aeruginosa produces a D
      galactophilic (PA-IL) lectin and another lectin (PA-IIL) that binds L-fucose > D
      arabinose > D-mannose in close association with its host-attacking factors. These
      lectins contribute to the virulence of P. aeruginosa by their involvement in the
      production, adhesion, and pathogenic effects of its biofilm on host cells.
      Therefore, they are considered targets for anti-Pseudomonas therapy. The present
      study compares their blocking by human milk samples with that of the plant lectin
      Con A. It demonstrates that human milk inhibits the hemagglutinating activities
      of the three lectins, with PA-IIL much more strongly inhibited than PA-IL or Con
      A. Using these lectins, Western blots of the milk samples accord with the
      hemagglutination inhibition data and disclose the distribution of the human milk
      glycoproteins that inhibit each lectin. The data of this paper reveal the high
      efficiency of human milk components in blocking the P. aeruginosa lectins and the
      usefulness of these lectins for detecting milk glycoprotein saccharides, which
      may protect the infant against infections.

PMID- 12795412
TI  - A functional proteomics approach to signal transduction.
AB  - The purpose of this review is to highlight how proteomics techniques can be used
      to answer specific questions related to signal transduction in a wide variety of
      systems. In our laboratory, we utilize proteomic technologies to elucidate signal
      transduction pathways involved in smooth muscle contraction and relaxation, cell
      growth and tumorigenesis, and the pathogenesis of malaria. We see the real
      application of this technology as a tool to enhance the power of existing
      approaches such as classical yeast and mouse genetics, tissue culture, protein
      expression systems, and site-directed mutagenesis. Our basic approach is to
      examine only those proteins that differ by some variable from the control sample.
      In this way, the number of proteins to be processed by electrophoresis, Edman
      degradation, or mass spectrometry is greatly reduced. In addition, since only
      those proteins that change in response to a given biological treatment are
      analyzed, the experimental outcome provides information about specific signaling
      pathways. Examples of typical experiments in our laboratory are measurement of
      changes in protein phosphorylation in response to treatment of cells with growth
      factors or specific drugs, characterization of proteins associated with a bait
      protein in a "pull-down" experiment, or measurement of changes in protein
      expression. Frequently, in these experiments, it is necessary to define complex
      protein mixtures. To achieve this goal, we utilize a variety of techniques to
      isolate specific types of proteins or "subproteomes" for further analysis. In
      this review, we discuss strategies used in our laboratory for studying signaling
      pathways, including subproteome isolation, proteome mining, and analysis of the
      phosphoproteome.

PMID- 12795413
TI  - The use of DNA microarrays to assess clinical samples: the transition from
      bedside to bench to bedside.
AB  - The advent of gene array technology brings the ability to classify disease states
      to the molecular level by examining changes in all mRNAs expressed in cells or
      tissues. Comparing changes in gene expression patterns between normal and
      diseased cells and/or tissues has elucidated unique subsets of genes identifiable
      to a specific disease. Already, new subclassifications of specific cancers have
      been discovered, belying that genomic profiling can uniquely distinguish a
      specific disease state and tissue of origin. This technology bestows the ability
      to examine global changes occurring in a cell or tissue(s), thereby allowing the
      elucidation of alterations in dysregulated biological, biochemical, and molecular
      events leading to disease states such as diabetes, hypertension, infertility,
      obesity, osteoporosis, and atherosclerosis. Furthermore, genomic profiling will
      lead to new molecular targets for the development of drug therapeutics.
      Futuristically, one could envision personalized patient therapies based upon
      identification of specific aberrant signaling pathways that can be targeted for
      drug therapy.

PMID- 12795414
TI  - Gene expression profiling for prediction of clinical characteristics of breast
      cancer.
AB  - We have applied techniques of gene expression analysis to the analysis of human
      breast cancer by identifying metagene models with the capacity to discriminate
      breast tumors based on estrogen receptor (ER) status as well as the propensity
      for lymph node metastasis. We assess the utility and validity of these models in
      predicting status of tumors in cross-validation determinations. The practical
      value of such approaches relies on the ability not only to assess relative
      probabilities of clinical outcomes for future samples but also to provide an
      honest assessment of the uncertainties associated with such predictive
      classifications, based on the selection of gene subsets for each validation
      analysis. This latter point is of critical importance to the ability of applying
      these methodologies to clinical assessment of tumor phenotype. It is also clear
      from ER predictions that these analyses identify genes known to be involved in ER
      function but also identify new candidate genes involved in ER function. We
      believe these gene expression phenotypes have the potential to characterize the
      complex genetic alterations that typify the neoplastic state in a way that truly
      reflects the complexity of the regulatory pathways that are affected.

PMID- 12795415
TI  - Statistical approach to DNA chip analysis.
AB  - Statistical methods for analyzing data from DNA microarray experiments are
      reviewed. Specifically, we discuss common experimental setups, methods for data
      reduction and clustering, and analysis of time-course experiments. While early
      microarray studies focused mainly on the basic methodological and technical
      aspects of DNA arrays, emphasis has shifted to biological, medical, and clinical
      applications. We mention several of these and present results from our recent
      research as illustrative examples. New developments in this ever-growing field
      are outlined.

PMID- 12795416
TI  - Identification of a nuclear factor kappa B-dependent gene network.
AB  - Nuclear factor-kappa B (NF-kappaB) is a highly inducible transcription factor
      that plays an important role in the hepatic acute-phase response, innate/adaptive
      immunity, and cellular survival through the induction of genetic networks. The
      major transcriptional-activating species Rel A-NF-kappaB is a cytoplasmic complex
      whose nuclear translocation is controlled by its association with a family of
      inhibitory proteins, termed IkappaBs. Activation of NF-kappaB results in the
      targeted proteolysis of IkappaB, releasing NF-kappaB to enter the nucleus and
      bind to specific sequences in target promoters. Because the genomic actions of NF
      kappaB are influenced by the stimulus applied and the promoter context/chromatin
      structure in which it binds, the spectrum of NF-kappaB-regulated genes has not
      been elucidated. We have begun to address this question, exploiting a tightly
      regulated cellular system expressing a nondegradable IkappaBalpha mutant that
      completely inhibits NF-kappaB action. High-density oligonucleotide microarrays
      were used to identify genetic responses in response to complex biological stimuli
      (viral replication) in the presence and absence of NF-kappaB. Using statistical
      and informatics tools, we identified two groups of NF-kappaB-dependent genes with
      distinct expression profiles: 1) a group with high constitutive expression whose
      expression levels fall in response to viral exposure and constitutive mRNA
      expression increases from NF-kappaB blockade, and 2) a group where constitutive
      expression was very low (or undetectable) and, after stimulation, expression
      levels strongly increased. In this group, NF-kappaB blockade inhibited the viral
      induction of genes. This latter cluster includes chemokines, transcriptional
      regulators, intracellular proteins regulating translation and proteolysis, and
      secreted proteins (e.g., complement components, growth factor regulators). These
      data reveal complexity in the genetic response to NF-kappaB and serve as a
      foundation for further informatics analysis to identify genetic features common
      to up- and downregulated NF-kappaB-dependent promoters.

PMID- 12795417
TI  - Role of defective apoptosis in type 1 diabetes and other autoimmune diseases.
AB  - Lymphocyte development, selection, and education are strictly controlled to
      prevent autoimmunity, with potentially autoreactive cells being removed by
      apoptosis. Dysregulation of apoptosis is a central defect in diverse murine
      autoimmune diseases. In murine models of autoimmune lupus, for example, mutations
      in the death receptor Fas (CD95) or in its ligand, FasL (CD95L), have been
      identified and shown to render lymphoid cells resistant to apoptosis. In
      contrast, select lymphoid subpopulations of mice with autoimmune diabetes
      manifest an increased susceptibility to apoptosis as a result of impaired
      activation of the transcription factor nuclear factor-kappa B (NF-kappaB), which
      normally protects cells against tumor necrosis factor-alpha (TNF-alpha)-induced
      apoptosis. The genetic basis of this defect in NF-kappaB activation is a mutation
      in the promoter-enhancer region of a gene that encodes an essential subunit
      (LMP2) of the proteasome. Although no specific genetic defects have been
      identified in most common forms of human autoimmune disease, functional assays
      consistently demonstrate heightened apoptosis attributable to multiple death
      signaling pathways.

PMID- 12795418
TI  - Genomic analysis of glucocorticoid-regulated promoters in murine T-lymphoma
      cells.
AB  - We have undertaken a high-throughput analysis to identify targets of
      glucocorticoid regulation in P1798 murine T-lymphoma cells. G1/S-arrested
      cultures were treated for 8 hours with 0.1 microM dexamethasone (dex) in the
      presence and absence of 1 microg/ml cycloheximide. Untreated cultures and
      cultures exposed to cycloheximide alone were prepared as controls. RNA was
      isolated and gene expression analyzed using Affymetrix MG-U74A oligonucleotide
      arrays (Gene Chips). Three independent experiments were performed. The data were
      analyzed using a variety of statistical and analytical approaches in order to
      identify primary transcriptional targets of the glucocorticoid receptor. We
      identified 44 genes that increase by > 2-fold in both dex-treated and dex +
      cycloheximide-treated cultures (relative to control and cycloheximide-treated
      cultures) in three replicate experiments. Statistical analysis of control data
      indicate that the probability that a given probeset would, as a result of random
      error, increase > 2-fold both in the presence and absence of cycloheximide in two
      independent experiments is approximately 7 x 10(-9). We have retrieved from the
      Celera mouse genomic sequence 8 kb of promoter sequence, spanning 4 kb either
      side of the 5'-end of the cDNA from eight of the induced genes. These sequences
      were analyzed for potential glucocorticoid receptor binding sites. Five of these
      genes contain the sequence ACAnnnTGTnCT within 4 kb of the presumptive
      transcriptional start site. Eight control genes were selected at random and
      analyzed for the sequence ACAnnnTGTnCT. Two control genes had such sequences
      within 4 kb of the transcriptional start site.

PMID- 12795419
TI  - Regulation of a distinctive set of genes in glucocorticoid-evoked apoptosis in
      CEM human lymphoid cells.
AB  - Gene expression was evaluated in clones of the acute lymphoblastic leukemic cell
      line CEM that were sensitive or resistant to apoptosis evoked by the
      glucocorticoid, dexamethasone (Dex). Founding clones CEM-C7 (glucocorticoid
      sensitive) and CEM-C1 (glucocorticoid resistant) were subcloned to maximize
      uniformity of each population studied. Among subclones of C1, our original
      pseudodiploid clone of glucocorticoid-resistant cells, we found a high proportion
      of hyperploid clones. Most C1 subclones were glucocorticoid resistant but two C1
      subclones were found to be revertants to glucocorticoid sensitivity.
      Glucocorticoid receptor content of the C1 subclones varied almost 5-fold but
      higher quantity of receptors did not guarantee steroid sensitivity. Gene
      expression analysis was carried out on microchips containing representations for
      approximately 12,600 human genes. When a group of four subclones from C1 (three
      glucocorticoid-resistant and one glucocorticoid-sensitive revertant) were
      compared with the glucocorticoid-sensitive subclone CEM-C7-14 for basal gene
      expression, the four C1 subclones clustered closely and far from C7-14. Thus,
      basal gene expression in the C1 subclones differed for a large number of genes
      from that in the C7 subclone. Reversion to glucocorticoid sensitivity did not
      cause a major shift in basal gene expression to a more C7-like state. Three
      clones (one revertant glucocorticoid sensitive from C1 subclone, one C7 sensitive
      subclone, and one C1 glucocorticoid-resistant subclone) were compared for the
      genes regulated by treatment for 20 hours with 10(-6)M Dex. This interval brings
      the cells to a point just before the onset of apoptosis. We tested the hypothesis
      that a distinctive set of genes would be regulated in the glucocorticoid
      sensitive clones. This proved to be so. In three experiments, at our chosen
      levels of discrimination, 39 genes were consistently induced > or = 2.5-fold and
      21 genes were consistently reduced > or = 2-fold in glucocorticoid-sensitive
      clones but not in the glucocorticoid-resistant clone. The glucocorticoid
      resistant clone showed induction or reduction of 88 genes different from those
      regulated in the glucocorticoid-sensitive clones. These data support our
      hypothesis and further show that the glucocorticoid-resistant clone is capable of
      responding to steroid but with a different set of genes. We propose that a
      general metabolic switch accounts for the alteration.

PMID- 12795420
TI  - Overlapping but distinct profiles of gene expression elicited by glucocorticoids
      and progestins.
AB  - Glucocorticoids and progestins bind to receptors that share many structural and
      functional similarities, including virtually identical DNA recognition
      specificity. Nonetheless, the two hormones mediate very distinct biological
      functions. For example, progestins are associated with the incidence and
      progression of breast cancer, whereas glucocorticoids are growth suppressive in
      mammary cancer cells. To understand the mechanisms that engender biological
      specificity, we have employed two systematic approaches to identify genes that
      are differentially regulated by the two hormones. The first strategy is to
      utilize Affymetrix oligonucleotide arrays to compare glucocorticoid- and
      progestin-regulated gene expression in a human breast cancer cell line. This
      global analysis reveals that the two hormones regulate overlapping but distinct
      sets of genes, including 31 genes that are differentially regulated.
      Surprisingly, the set of differentially regulated genes was almost as large as
      the set of genes regulated by both hormones. Examination of the set of
      differentially regulated genes suggests mechanisms behind the distinct growth
      effects of the two hormones in breast cancer. The differential regulation of four
      genes representing different regulatory patterns was confirmed by reverse
      transcription-polymerase chain reaction (RT-PCR) and Northern blot analyses.
      Treatment with cycloheximide or mifepristone (RU486) indicates that the
      regulation is a primary, receptor-mediated event. The second strategy is to
      employ a retroviral promoter trap and Cre/loxP-mediated, site-specific
      recombination to identify genes that are differentially regulated by
      glucocorticoids and progestins. A mouse fibroblast cell line (4F) stably
      expressing both glucocorticoid receptor (GR) and progesterone receptor (PR) and
      containing a single copy of a multifunctional selection plasmid was generated.
      This line was transduced with a self-inactivating retroviral promoter trap vector
      carrying coding sequences for Cre-recombinase (Cre) in the U3 region. Integration
      of the provirus places Cre expression under the control of genomic flanking
      sequence. Activation of Cre expression from integration into active genes results
      in a permanent switch between the selectable marker genes that convert the cells
      from neomycin resistant to hygromycin resistant. Selection for hygromycin
      resistance after hormone treatment yields recombinants in which Cre sequences in
      the U3 region are expressed from hormone-inducible, upstream cellular promoters.
      Because Cre-mediated recombination is a permanent event, the expression of the
      selectable marker genes is independent of ongoing Cre expression. Thus, this
      system permits the identification of genes that are transiently or weakly induced
      by hormone. Detailed analyses of genes identified in these studies will furnish a
      mechanistic understanding of differential regulation by glucocorticoids and
      progestins.

PMID- 12795421
TI  - Analysis of gene expression in the normal and malignant cerebellum.
AB  - The developing nervous system consists of a small number of multipotent
      precursors that undergo extensive proliferation to generate the neurons and glia
      that make up the adult brain. Elucidating the mechanisms that control the growth
      and differentiation of these cells is important not only for understanding normal
      neural development but also for understanding the etiology of central nervous
      system tumors. A particularly striking example of this is in the cerebellum.
      Recent studies have suggested that the Sonic hedgehog-Patched signaling pathway
      plays a critical role in regulating the proliferation of cerebellar granule cell
      precursors and is also a major target of mutation in the cerebellar tumor
      medulloblastoma. In light of these observations, identification of additional
      genes that control cerebellar growth and differentiation is likely to provide
      important insight into the basis of cerebellar tumors. Similarly, analysis of
      gene expression in medulloblastoma will no doubt shed light on previously unknown
      signaling pathways that regulate normal cerebellar development. The advent of
      high-throughput gene expression analysis techniques--such as adapter-tagged
      competitive polymerase chain reaction (ATAC-PCR), serial analysis of gene
      expression (SAGE), and DNA microarrays--makes identification of such genes faster
      and easier than ever before. This review summarizes recent studies of gene
      expression in the cerebellum and discusses the value of such approaches for
      understanding development and tumorigenesis in this tissue.

PMID- 12795422
TI  - Paired-like repression/activation in pituitary development.
AB  - Pituitary gland development is controlled by signals that guide expression of
      specific combinations of transcription factors that dictate serial determination
      and differentiation events. One class of factors is paired-like homeodomain
      factors. Two that have been investigated are the repressor Hex1/Rpx and activator
      prophet of Pit-1 (Prop-1), which exert selective roles during pituitary
      development. The opposing actions of these factors provide one aspect of
      pituitary organogenesis.

PMID- 12795423
TI  - Dynamic changes in gene expression during human trophoblast differentiation.
AB  - The genetic program that directs human placental differentiation is poorly
      understood. In a recent study, we used DNA microarray analyses to determine genes
      that are dynamically regulated during human placental development in an in vitro
      model system in which highly purified cytotrophoblast cells aggregate
      spontaneously and fuse to form a multinucleated syncytium that expresses
      placental lactogen, human chorionic gonadotropin, and other proteins normally
      expressed by fully differentiated syncytiotrophoblast cells. Of the 6918 genes
      present on the Incyte Human GEM V microarray that we analyzed over a 9-day
      period, 141 were induced and 256 were downregulated by more than 2-fold. The
      dynamically regulated genes fell into nine distinct kinetic patterns of induction
      or repression, as detected by the K-means algorithm. Classifying the genes
      according to functional characteristics, the regulated genes could be divided
      into six overall categories: cell and tissue structural dynamics, cell cycle and
      apoptosis, intercellular communication, metabolism, regulation of gene
      expression, and expressed sequence tags and function unknown. Gene expression
      changes within key functional categories were tightly coupled to the
      morphological changes that occurred during trophoblast differentiation. Within
      several key gene categories (e.g., cell and tissue structure), many genes were
      strongly activated, while others with related function were strongly repressed.
      These findings suggest that trophoblast differentiation is augmented by
      "categorical reprogramming" in which the ability of induced genes to function is
      enhanced by diminished synthesis of other genes within the same category. We also
      observed categorical reprogramming in human decidual fibroblasts decidualized in
      vitro in response to progesterone, estradiol, and cyclic AMP. While there was
      little overlap between genes that are dynamically regulated during trophoblast
      differentiation versus decidualization, many of the categories in which genes
      were strongly activated also contained genes whose expression was strongly
      diminished. Taken together, these findings point to a fundamental role for
      simultaneous induction and repression of mRNAs that encode functionally related
      proteins during the differentiation process.

PMID- 12795424
TI  - Regulation of hematopoietic stem cell self-renewal.
AB  - Every day, billions of new blood cells are produced in the body, each one derived
      from a hematopoietic stem cell (HSC). Because most mature blood stem cells have a
      limited life span, the ability of HSCs to perpetuate themselves through self
      renewal and generate new blood cells for the lifetime of an organism is critical
      to sustaining life. A key problem in hematopoietic stem cell biology is how HSC
      self-renewal is regulated. Recent evidence suggests that signaling pathways
      classically involved in embryonic development--such as the Wnt signaling pathway-
      play an important role in regulating stem cell self-renewal. The Wnt signaling
      pathway has been shown to regulate stem cell fate choice in a variety of organs,
      including the skin, the nervous system, and the hematopoietic system. In the
      hematopoietic system, stimulation of hematopoietic progenitors and stem cells
      with soluble Wnt proteins or downstream activators of the Wnt signaling pathway
      leads to their expansion. Future studies focusing on the mechanism of action of
      the Wnt signaling pathway and its interaction with other pathways are needed to
      gain further insight into the regulation of stem cell self-renewal, not only in
      the hematopoietic system but also in a variety of other tissues.

PMID- 12795425
TI  - Investigation of the transcriptional changes underlying functional defects in the
      mammary glands of prolactin receptor knockout mice.
AB  - Knockout (KO) mice have been created that carry null mutations of genes encoding
      molecules essential for prolactin (PRL) release, PRL, the receptor for prolactin
      (PRLR), and various members of the receptor's signaling pathway. This allowed an
      in vivo genetic analysis of the role of PRL in target organ function. In PRLKO
      and PRLRKO mice, mammary ductal side branching was absent, terminal end bud (TEB)
      like structures persisted at the ductal termini well into maturity, and no
      alveolar buds formed along the ductal tree. Transplants of recombined mammary
      glands formed from stromal and epithelial elements with and without PRLR showed
      normal development, while supplementation of progesterone levels in PRLKO animals
      restored ductal side branching. During pregnancy, PRLR heterozygous animals
      initially showed normal ductal and alveolar development. However, alveolar
      development stalled during late pregnancy, preventing successful lactation. This
      defect could be rescued by the loss of a single allele of the suppressor of
      cytokine signaling (SOCS) 1 gene. Transplants of recombined glands containing
      PRLRKO epithelium and wild-type (WT) stroma formed alveolar buds during pregnancy
      but showed no lobuloalveolar development. Recombinations of WT epithelium and
      PRLRKO stroma showed normal development, demonstrating that a direct action of
      the lactogenic hormones is confined to the epithelium, to promote lobuloalveolar
      development. Transcript profiling of epithelial transplants expressing or not
      expressing PRLR was used during early pregnancy to investigate the
      transcriptional response to lactogens underlying this defect. Such profiling has
      identified a number of genes with well-characterized roles in mammary
      development, in addition to a number of novel transcripts.

PMID- 12795426
TI  - Microarray analysis and identification of novel molecules involved in insulin
      like growth factor-1 receptor signaling and gene expression.
AB  - The insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-1R)
      are members of the same subfamily of receptor tyrosine kinases. The two receptors
      phosphorylate many of the same substrates and activate the same signaling
      modules, including the mitogen-activated protein kinase (MAPK) and phosphatidyl
      inositol 3' kinase (PI3K) signaling pathways. Although the IR and IGF-1R share
      some redundant functions in metabolism, cell growth, differentiation, and
      apoptosis, they also exhibit distinct physiological roles. Some of these may be
      due to differences in tissue distribution, receptor structure, formation of
      hybrid receptors, or mechanisms of ligand binding. However, the divergent effects
      of insulin and IGF-1 also may be explained by specificity in the intracellular
      signals generated by insulin and IGF-1. In particular, the IR and IGF-1R are
      capable of triggering their own biological responses by using specific or
      preferential substrates, molecular adapters, or signaling pathways. In a recent
      study, we used cDNA microarray analysis to identify genes differentially
      regulated by insulin and IGF-1. Mouse NIH-3T3 fibroblasts expressing either the
      wild-type human IGF-1R or IR were stimulated with either IGF-1 or insulin,
      respectively. We identified 39 genes differentially regulated by insulin and IGF
      1. Most of these genes had not been reported previously to be responsive to
      insulin or IGF-1. The genes induced by IGF-1 generally were involved in
      mitogenesis or differentiation, while the genes found to be induced by insulin
      did not conform to any particular category. In a separate study, immortalized
      breast epithelial cells were stimulated with IGF-1 and a cDNA microarray analysis
      was used to generate a profile of IGF-1-regulated genes. A number of genes known
      to be involved in angiogenesis were found to be regulated by IGF-1. These results
      strongly suggest that this technology may be extremely useful in identifying
      groups of genes that are specifically regulated by different ligands and their
      activated receptors.

PMID- 12795427
TI  - Consequences of elevated luteinizing hormone on diverse physiological systems:
      use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation
      induced pathophysiology.
AB  - Chronically elevated luteinizing hormone (LH) induces significant pathology in
      the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha
      (alpha)-subunit promoter to direct transgene expression specifically to
      gonadotropes in the anterior pituitary. Previously, it was shown that female
      LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors,
      and undergo precocious puberty from elevated LH and steroid hormones that fail to
      completely repress the alpha-subunit promoter. This chapter will discuss recent
      studies that further elucidate the impact of chronically elevated LH on diverse
      physiological systems. Granulosa cell tumors induced by elevated LH are strain
      dependent and prevented when transgenics are treated with human chorionic
      gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is
      generated, revealing several possible gene candidates for ovarian granulosa cell
      tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and
      oocytes exhibit increased rates of meiotic segregation defects, although meiotic
      competency is acquired normally. Anovulation can be rescued in transgenics by
      superovulation, though pregnancy fails at midgestation due to maternal factors.
      Uterine receptivity defects prevent implantation of normal embryos following
      induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical
      hyperfunction with increased corticosterone production following induction of
      adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the
      gonads and the adrenal gland, when expressed in conjunction with the inhibin
      alpha SV40 transgene. Finally, chronic elevated LH promotes mammary
      tumorigenesis. The understanding of multiple clinical pathologies--including
      ovarian cancer, perimenopausal reproductive aging, premature ovarian failure,
      polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be
      enhanced through further study of this useful transgenic mouse model.

PMID- 12795428
TI  - Posterior continuous curvilinear capsulorhexis with and without optic capture of
      the posterior chamber intraocular lens in the absence of vitrectomy.

PMID- 12795429
TI  - Amblyopia.

PMID- 12795430
TI  - The malpractice crisis.

PMID- 12795431
TI  - Organoid nevus syndrome: manifestations and management.

PMID- 12795432
TI  - Evolution of ocular manifestations in nephropathic cystinosis: a long-term study
      of a population treated with cysteamine.
AB  - BACKGROUND: Nephropathic cystinosis is characterized by an accumulation of
      cystine crystals within most body tissues. Renal transplantation and oral
      cysteamine have improved the general prognosis of the disease, and ocular
      manifestations are now the most common complication. This long-term follow-up
      study describes the sequence of ocular manifestations in patients with
      nephropathic cystinosis treated with oral and topical cysteamine. METHODS: Data
      were recorded for all patients with cystinosis examined between 1980 and 2000.
      For each patient, photophobia and visual acuity were evaluated and slit-lamp and
      fundus examinations were performed. For some patients, an electroretinogram was
      also performed. RESULTS: Twenty-nine patients were observed during this period.
      They received oral and topical cysteamine. Photophobia and loss of visual acuity
      generally began by 10 years of age but were severe only after 15 years of age.
      Peripheral corneal epithelial infiltration appeared in the first few years of
      life. Infiltration evolved toward the depth and center of the cornea during the
      second decade of life. Retinopathy was present in 51.7% of the patients, with 3
      cases of maculopathy and 3 cases of flattening on electroretinogram. CONCLUSIONS:
      Photophobia and corneal infiltration, although generally severe after 15 years of
      age, could be treated with topical cysteamine and corneal transplantation.
      Retinal infiltration, previously described as frequent and potentially blinding,
      is currently observed in only half of these patients, with mild visual
      impairment. This could be related to the treatment with oral cysteamine reaching
      the retinal vascularization.

PMID- 12795433
TI  - Factors predicting upshoots and downshoots in Duane's retraction syndrome.
AB  - PURPOSE: Factors predicting mechanical and innervational types of upshoots and
      downshoots in Duane's retraction syndrome were evaluated. METHODS: This
      retrospective study evaluated upshoots and downshoots in 196 patients (222 eyes)
      with Duane's retraction syndrome seen between January 1990 and July 2001. On the
      basis of the clinical characteristics, upshoots and downshoots were classified as
      mechanical type, innervational type, or both. Factors potentially predicting the
      upshoot-downshoot phenomenon that were studied included patient age, type of
      Duane's retraction syndrome, horizontal strabismus, and vertical tropia in the
      primary position of gaze. RESULTS: Upshoots and downshoots were present in 39% of
      the eyes. The mechanical type was more common than the innervational type (26% vs
      12%). Overall, upshoots and downshoots were statistically significantly more
      common in type III Duane's retraction syndrome, with exotropia, and with vertical
      tropia in primary position. Patient age had no correlation with upshoots or
      downshoots. Both types of upshoots and downshoots were significantly more common
      in type III Duane's retraction syndrome. A statistically significant association
      was found between exotropia and the mechanical type, and between vertical tropia
      in primary position and the innervational type. CONCLUSIONS: All patients with
      type III Duane's retraction syndrome, exotropia, and vertical tropia in the
      primary position of gaze should be examined for upshoots and downshoots. One
      should look specifically for the mechanical type when there is exotropia and for
      the innervational type when there is a large vertical tropia in the primary
      position of gaze.

PMID- 12795434
TI  - 2-octyl cyanoacrylate adhesive for conjunctival wound closure in rabbits.
AB  - PURPOSE: To evaluate the efficacy and histology of 2-octyl cyanoacrylate in
      conjunctival wound closure in rabbits. METHODS: Ten eyes of 10 New Zealand white
      rabbits were used. Eight rabbits had conjunctival wounds that were repaired with
      2-octyl cyanoacrylate. Two rabbits were killed at 1 week and two rabbits were
      killed at 2 weeks and their conjunctivae were examined histologically. From two
      additional rabbits, conjunctival strips were obtained that underwent tensile
      strength testing. RESULTS: All conjunctival wounds closed well with 2-octyl
      cyanoacrylate. Histology revealed minimal inflammation of the wounds. The tensile
      strength of conjunctival strips glued together was 25.5 g (standard deviation,
      1.9 g). CONCLUSION: 2-Octyl cyanoacrylate may be a possible tissue adhesive for
      conjunctival wound closure.

PMID- 12795435
TI  - Fibrin glue for conjunctival closure in strabismus surgery.

PMID- 12795436
TI  - Bilateral retinoblastoma presenting with simultaneous phthisis bulbi and
      buphthalmos.

PMID- 12795437
TI  - Acquired choroidoretinal anastomosis complicating strabismus surgery.

PMID- 12795438
TI  - Juvenile xanthogranuloma of the iris as the first manifestation of a
      neurofibromatosis.

PMID- 12795439
TI  - Junctional epidermolysis bullosa in a young patient.

PMID- 12795440
TI  - Conservative management of globe luxation associated with congenital orbital
      venous anomaly.

PMID- 12795441
TI  - A clinicopathologic study of sinus histiocytosis with massive lymphadenopathy
      mimicking an optic nerve tumor.

PMID- 12795442
TI  - Paroxysmal tonic upgaze associated with proprioceptive stimulation.

PMID- 12795443
TI  - Early ocular manifestations in an infant with carbohydrate-deficient glycoprotein
      syndrome type Ia.

PMID- 12795444
TI  - Dissociated vertical deviation associated with Duane's syndrome.

PMID- 12795445
TI  - Emerging evidence on the role of soy in reducing prostate cancer risk.
AB  - Soyfoods are a unique dietary source of isoflavones, which have both hormonal and
      non-hormonal effects relevant to prostate cancer prevention. In vitro, the main
      soybean isoflavone, genistein, inhibits prostate cancer cell growth; in animals,
      most but not all studies show isoflavonel rich soy protein and isolated
      isoflavones inhibit prostate tumor development. Currently, although only limited
      epidemiologic data indicate soy intake reduces prostate cancer risk, results from
      a pilot intervention trial suggest isoflavones may be beneficial to prostate
      cancer patients. For several reasons, men concerned about their prostate health
      may consider incorporating soy into their diet.

PMID- 12795446
TI  - Small intestinal bacterial overgrowth: a possible risk factor for metabolic bone
      disease.
AB  - Small intestinal bacterial overgrowth (SIBO) is one of the causes of
      malabsorption syndromes. The prevalence of metabolic bone disease in patients
      with SIBO is unknown, but a recent prospective case-control study indicated
      significant contribution of SIBO to the development of metabolic bone disease. We
      review this and other reports in the literature and discuss the possible
      mechanisms causing metabolic bone disease in patients with SIBO.

PMID- 12795447
TI  - Interrelationship between diabetes and homocysteine metabolism: hormonal
      regulation of cystathionine beta-synthase.
AB  - Plasma homocysteine levels are elevated during diabetes when there is
      atherosclerosis or insufficient renal function; however, diminished plasma
      homocysteine concentrations are observed in diabetes without complications.
      Recent studies have demonstrated that under diabetic conditions, the catabolism
      of homocysteine was enhanced by transcriptional regulation of hepatic
      cystathionine beta-synthase and these changes were prevented by treatment with
      insulin.

PMID- 12795448
TI  - Does overweight in childhood have an impact on adult health?
AB  - The consequences of overweight in childhood, including persistence into adulthood
      and as a risk factor for adverse health consequences, are of substantial concern
      given the recent upward trend in prevalence. A recent report on an historic
      cohort--a British 1947 birth cohort--is largely consistent with previous
      estimates of persistence of overweight. Long-term health consequences of obesity
      were not demonstrable in this study, likely owing to the small numbers of
      subjects who were overweight during post-World War II Britain.

PMID- 12795449
TI  - Predicting energy requirements in the clinical setting: are current methods
      evidence based?
AB  - Estimating energy requirements is necessary in clinical practice when indirect
      calorimetry is impractical. This paper systematically reviews current methods for
      estimating energy requirements. Conclusions include: there is discrepancy between
      the characteristics of populations upon which predictive equations are based and
      current populations; tools are not well understood; and patient care can be
      compromised by inappropriate application of the tools. Data comparing tools and
      methods are presented and issues for practitioners are discussed.

PMID- 12795450
TI  - Effects of trace components of dietary fat on cholesterol metabolism:
      phytosterols, oxysterols, and squalene.

PMID- 12795451
TI  - Believe in iron.

PMID- 12795452
TI  - Making sense of gut contents.

PMID- 12795453
TI  - A proton-pump inhibitor, rabeprazole, improves ventilatory function in patients
      with asthma associated with gastroesophageal reflux.
AB  - BACKGROUND: Treatment of gastroesophageal reflux (GER) with proton-pump
      inhibitors (PPI) improves symptoms of asthma in some patients. However, the
      effects of a PPI on ventilatory function are still controversial. In this study,
      we measured ventilatory function in asthma patients treated with a PPI in order
      to identify those in whom a therapeutic effect on asthma can be expected from the
      acid suppression. METHODS: From a cohort of 114 consecutive patients with
      bronchial asthma, 53 patients agreed to participate in the study and were treated
      with rabeprazole 20mg daily for 8 weeks during an asymptomatic, stable period
      with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as
      GER on the basis of the QUEST questionnaire and endoscopic examination. The
      patients were monitored for improvement in ventilatory function. RESULTS: Four
      patients dropped out because of adverse drug reactions. All the patients with GER
      noted an improvement in reflux symptoms with PPI treatment. An improvement of
      more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients
      but in none of the non-GER patients. Factors predictive of improvement in PEF
      with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06
      2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI:
      0.001-0.31, P = 0.008). CONCLUSIONS: Treatment with rabeprazole is expected to
      ameliorate asthma in non-steroid-dependent patients who have symptomatic GER
      defined by the QUEST score.

PMID- 12795454
TI  - Effect of pantoprazole on the course of reflux-associated laryngitis: a placebo
      controlled double-blind crossover study.
AB  - BACKGROUND: The optimal management of patients with reflux-associated laryngitis
      is unclear. We performed a placebo-controlled crossover trial in patients with
      proven reflux disease and associated laryngitis to determine the effect of
      pantoprazole and to gain information on the natural course of the disease.
      METHODS: Sixty-two consecutive non-smoking patients with hoarseness and proven
      laryngitis were examined. Scores with respect to the larynx and for subjective
      complaints were determined and 24-h pH-metry to assess acid reflux in the lower
      oesophagus and pharynx was performed. Patients with pathologic reflux were given
      the chance to enter a double-blinded randomized crossover trial with pantoprazole
      40 mg b.i.d. and placebo for a duration of 3 months each, separated by a 2-week
      washout period. RESULTS: Twenty-four of 62 patients showed pathological reflux;
      21 patients were included in the study and 14 concluded all parts of the study.
      Both pantoprazole and placebo resulted in a marked improvement in laryngitis
      scores (decrease of 8.0 +/- 1.4 versus 5.6 +/- 2.6; no significant difference
      between the 2 treatments) and symptoms after the first 3 months (decrease of
      oesophageal symptom score of 2.2 +/- 1.4 versus 5.4 +/- 2.8; decrease of
      laryngeal scores of 8.3 +/- 3.6 versus 10.3 +/- 3.9; also no significant
      difference between the 2 treatments). A second pH-metry 2 weeks thereafter proved
      the persistence of reflux in most of these patients. Switching to pantoprazole
      led to a further improvement of scores. In the group switched to placebo there
      was recurrence only in a minority of patients. CONCLUSIONS: The self-limited
      nature of reflux-associated laryngitis in non-smokers is largely underestimated.
      Laryngitis improves despite the persistence of reflux. Pantoprazole may be
      helpful especially in relieving acute symptoms, but the advantage of long-term
      treatment over placebo has been greatly overestimated.

PMID- 12795455
TI  - Pioglitazone, a specific ligand of the peroxisome proliferator-activated receptor
      gamma reduces gastric mucosal injury induced by ischaemia/ reperfusion in rat.
AB  - BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      ligand-dependent nuclear receptor that has been implicated in the control of
      metabolism and numerous cellular processes, including cell cycle control,
      carcinogenesis, and inflammation. The present study was designed to investigate
      the effect of the specific PPARgamma ligand, pioglitazone, on the mucosal lesions
      induced by ischaemia and reperfusion (I/R) in rats. METHODS: I/R lesions were
      induced in Wistar rats by applying a small clamp to the coeliac artery for 30 min
      (ischaemic phase), followed by the removal of the clamp for 3 h (reperfusion
      phase). Vehicle (saline) or increasing doses of pioglitazone (2.5, 10, and 30
      mg/kg i.g.) were given 30 min before exposure to I/R. The animals were killed
      immediately after the end of the reperfusion phase (time 0) and at 12 and 24h
      after I/R. The area of gastric lesions was measured by planimetry, and the
      gastric blood flow was determined by the H2 gas clearance method. The gastric
      mucosal gene expressions of PPARgamma, interleukin-1beta (IL-1beta), tumour
      necrosis factor alpha (TNF-alpha), leptin, cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) were examined by RT-PCR. In addition, protein expression
      of COX-2 and leptin was assessed by Western blot. RESULTS: The pretreatment with
      pioglitazone reduced in a dose-dependent manner the mean lesion area induced by
      I/R, and this effect was accompanied by a significant increase in the gastric
      blood flow. The decrease in gastric ulcerations by pioglitazone was also observed
      12 and 24 h after the I/R. The PPARgamma mRNA was weakly expressed in the intact
      gastric mucosa but significantly up-regulated after exposure to I/R at each time
      interval studied. The expression of IL-1beta was not changed significantly after
      pioglitazone applied i.g. at doses 2.5 and 10 mg/kg, but it was down-regulated at
      the dose 30mg/kg. TNFalpha mRNA was strongly increased after the exposure to I/R,
      but it was down-regulated after pioglitazone pretreatment. In contrast, both
      leptin and COX-2 mRNA and protein expression were increased in the gastric mucosa
      after exposure to I/R. The pretreatment with pioglitazone caused a significant up
      regulation of mRNA and protein expression of leptin, reaching its peak at the
      dose 30 mg/kg i.g. In contrast, COX-2 expression did not change significantly
      after the 2.5 and 10 mg/kg of pioglitazone, but it significantly decreased after
      pioglitazone at dose 30 mg/kg given to rats before exposure to I/R. CONCLUSIONS:
      Pioglitazone reduces the acute erosions and deeper gastric lesions induced by
      I/R. The beneficial effect of this PPARgamma ligand on I/R-induced gastric damage
      may be due to its anti-inflammatory properties, especially to the reduction in
      TNF-alpha expression and to up-regulation of leptin mRNA in the gastric mucosa.
      The inhibition of COX-2 expression by pioglitazone may reflect the anti
      inflammatory properties of this compound.

PMID- 12795456
TI  - Gastric carcinoid in a young woman with systemic lupus erythematosus and atrophic
      autoimmune gastritis.
AB  - BACKGROUND: Gastric carcinoid is a rare tumour that is associated with chronic
      atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th
      decade of life and is rarely diagnosed in patients under 30 years of age.
      METHODS: We describe a case of multiple gastric carcinoids in a 23-year-old woman
      with systemic lupus erythematosus and atrophic autoimmune gastritis--an
      association that has not been reported previously. RESULTS: The combination of
      atrophic autoimmune gastritis and gastric carcinoid with other autoimmune
      disorders has rarely been reported in the English medical literature. CONCLUSION:
      The fact that it mostly concerns (relatively) young patients may suggest a
      potential causative relation between those autoimmune disorders and the early
      development of atrophic gastritis with hypergastrinaemia, which subsequently
      leads to the occurrence of gastric carcinoid tumours at a young age.

PMID- 12795457
TI  - Do Japanese and Swedish peptic ulcer patients respond differently to Helicobacter
      pylori eradication therapies and what are their histological features?
AB  - BACKGROUND: As a consequence of gastric histological differences, Japanese and
      Swedish peptic ulcer (PU) patients may respond differently to Helicobacter pylori
      eradication therapies. METHODS: The study was single-blind and compared four
      eradication therapies in Japanese and Swedish patients with healed gastric (GU)
      or duodenal (DU) ulcer. Swedish patients received either (a)
      omeprazole+clarithromycin (OC, where O = 20 mg, C = 500 mg) for 2 weeks, or
      triple therapy with (b) omeprazole + amoxicillin + clarithromycin (OAC-L where O
      = 20mg, A = 1 g, C = 250 mg); (c) OAC-H (where O = 20 mg, A-1 g, C-500 mg); or
      (d) omeprazole + metronidazole + clarithromycin (OMC, where O = 20 mg, M = 400
      mg, C = 250 mg) for 1 week. Antibiotic doses were weight-adjusted downwards in
      Japanese patients. H. pylori was assessed using the urea breath test (UBT),
      histology and culture pre-entry, with UBT being repeated 4 and 8 weeks after
      stopping treatment. Histology and culture were repeated if the UBT was positive
      post-therapy. RESULTS: Recruitment included 120 patients from Japan (43 GU, 61
      DU, 16 GU+DU) and 120 from Sweden (119 DU, 1 GU+DU). There were 26 exclusions
      from a FAS analysis due to H. pylori negativity (14), no drug administration (7)
      or no data after visit 1 (5). Eradication rates (FAS) from Japan were (a) 63%,
      (b) 93%, (c) 96% or (d) 96%, and for Sweden (a) 92%, (b) 86%, (c) 93% or (d) 96%.
      Dual therapy was less effective in patients with gastric atrophy associated with
      GU disease. Tolerability was good in all treatment groups, with no serious
      adverse events. CONCLUSION: Triple therapies were safe and effective for H.
      pylori eradication in Japanese and Swedish peptic ulcer patients. Dual therapy
      was significantly less effective in the Japanese patients, half of whom had a
      history of GU and more abnormal histology than in the Swedish patients, all of
      whom had DU.

PMID- 12795458
TI  - Comparison of gastric histology among Swedish and Japanese patients with peptic
      ulcer and Helicobacter pylori infection.
AB  - BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between
      different ethnic groups. Gastric histopathology and the occurrence of H. pylori
      organisms in the stomach were investigated in healed duodenal (DU) and gastric
      (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial.
      METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological
      gastritis variables and H. pylori were assessed from biopsy specimens obtained
      using a specific sampling protocol and interpreted according to guidelines of the
      updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be
      very different between the recruited Japanese (39:55) and Swedish (0:109)
      patients. A comparison of data from SDU and JDU showed that the prevalence of H.
      pylori infection and the antral predominant gastritis demonstrated by both SDU
      and JDU were essentially identical. A comparison of data from JDU and JGU
      demonstrated a greater prevalence of H. pylori infection in the antrum, but not
      corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal
      metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all
      patients. CONCLUSIONS: The site specified biopsy methodology and standardized
      interpretation criteria utilized in this study clearly show that the
      histotopographic profile of Swedish and Japanese DU patients is essentially the
      same.

PMID- 12795459
TI  - Helicobacter pylori genotypes and expression of gastritis in erosive gastro
      oesophageal reflux disease.
AB  - BACKGROUND: Epidemiological studies suggest a negative association between
      Helicobacter pylori and gastro-oesophageal reflux disease (GORD). Moreover, cagA
      positive strains are reported to protect from complications of GORD. The aim of
      this study was to determine virulence factors (cagA, vacA and iceA) of H. pylori
      strains and the pattern of gastritis in patients with GORD in comparison with
      patients with duodenal ulcer (DU) or functional dyspepsia (FD). METHODS: H.
      pylori strains isolated from gastric biopsies of 105 consecutive patients with
      mild to moderate erosive GORD (n = 35, LA grade A-B), and from sex- and age
      matched patients with DU (n = 35) or FD (n = 35 without reflux symptoms) were
      investigated. CagA, vacA, and iceA genotypes were determined by PCR analysis of
      the isolates. Gastritis was classified in accordance with the updated Sydney
      classification. RESULTS: The prevalence of all three H. pylori virulence factors
      was higher in patients with GORD (cagA+ 80%, vacA s1 77%, iceA1 71%) and DU
      (cagA+ 83%, vacA s1 80%, iceA1 74%) than in patients with FD (cagA+ 40%, vacA s1
      49%, iceA1 46%). Gastritis activity in the antrum and corpus did not differ
      between the three groups. However, lymphocytic infiltration of the gastric antral
      mucosa was more pronounced in DU patients than in those with GORD or FD.
      CONCLUSIONS: H. pylori strains obtained from patients with mild to moderate
      erosive GORD show a virulence pattern similar to that found in DU patients. The
      presence of these virulence factors does not appear to protect against erosive
      lesions in the oesophagus.

PMID- 12795460
TI  - Psychological factors in irritable bowel syndrome: a population-based study of
      patients, non-patients and controls.
AB  - BACKGROUND: It has been suggested that psychopathology in irritable bowel
      syndrome (IBS) patients is a function of patient status rather than of the
      disease. Although there are many studies comparing IBS patients, IBS non
      patients, and controls with each other, no previous study has recruited all three
      groups from a representative community sample and had all subjects diagnosed by a
      physician. In the present study we aimed to compare psychological factors in IBS
      patients, IBS non-patients, and normal controls in a sample recruited from the
      population. METHODS: Subjects aged 18-45 years were recruited from a random
      sample of the normal population. Seventeen (2 M and 15 F) IBS patients were
      matched by sex and age with IBS non-patients and normals. Measures of personality
      traits, interpersonal distress, and temporary psychological distress were used. A
      physician diagnosed all 51 subjects in order to exclude possible gastrointestinal
      diagnoses other than IBS. RESULTS: Controls often differed from IBS non-patients
      and patients on the personality, interpersonal, and psychological distress
      measures, while IBS non-patients and patients very rarely differed from each
      other. All three groups were non-alexithymic. CONCLUSIONS: The results indicate
      that there are psychopathological differences between normals and IBS persons
      (patients and non-patients), but they could not confirm that psychopathology was
      a function of patient status. Whether this psychopathology is a vulnerability
      factor for IBS, or a consequence of it, remains to be studied.

PMID- 12795461
TI  - High frequency of coeliac disease among patients with autoimmune adrenocortical
      failure.
AB  - BACKGROUND: Coeliac disease (CD) is an autoimmune disease of the small intestine
      caused by gluten ingestion in genetically predisposed subjects. It can occur
      isolated or in combination with other autoimmune diseases. Autoimmune Addison's
      disease is frequently associated with other organ-specific autoimmune diseases.
      We have investigated the prevalence of CD among a large cohort of patients with
      autoimmune Addison's disease. METHODS: Seventy-six patients (44 women) with
      Addison's disease, 52% of whom had polyendocrine failure, were recruited from a
      registry of organ-specific autoimmune diseases in Norway. All sera were analysed
      for antibodies against gliadin (AGA), endomysium (EMA) and tissue
      transglutaminase (tTG). Patients with positive EMA and/or anti-tTG were offered
      endoscopy. The human leucocyte antigen (HLA) class II genotypes were determined.
      RESULTS: Five patients had antibodies against both endomysium and tissue
      transglutaminase. In these five patients, CD was verified by biopsy. One patient
      had known CD prior to the study. All six patients with CD carried the CD
      associated HLA haplotype DR3-DQ2. The total prevalence of CD was 7.9%.
      CONCLUSION: CD is frequently associated with Addison's disease. The risk of
      developing CD seems to be higher than can be explained by the common DR3-DQ2
      association alone. It is often asymptomatic or associated with unspecific
      symptoms. Addison patients should be screened for the presence of CD on a regular
      basis.

PMID- 12795462
TI  - Stressful life events, social support and confidence in the pregnant woman and
      risk of coeliac disease in the offspring.
AB  - BACKGROUND: Stressful life events just before conception or during pregnancy can
      affect fetal development and increase the risk of disease in the offspring. The
      purpose of our study was to examine stressful life events, maternal social
      support and confidence during pregnancy and the risk of coeliac disease in the
      offspring. METHODS: Prospective cohort study of 16,286 children born between 1
      October 1997 and 1 October 1999 in southeast Sweden. The study was part of the
      ABIS study (ABIS = All Babies In Southeast Sweden). Data on independent variables
      were obtained through questionnaires distributed at birth. The questionnaire
      included questions about parental disease, socio-economic factors, smoking,
      alcohol intake but also infections during pregnancy. Eight paediatric departments
      prospectively recorded all children with coeliac disease (confirmed through
      biopsy). RESULTS: Exposure to stressful life events (OR = 0.48: 95% CI OR = 0.12
      2.01; P = 0.318), lack of social support (OR = 3.17; 95% CI OR = 0.43-23.22; P =
      0.257) and lack of confidence (OR = 0.04; 95% CI OR = 0.00-2.48 x 10(9);P =
      0.794) in the pregnant woman were not linked to coeliac disease in the offspring.
      CONCLUSION: The study indicates that stressful life events, lack of social
      support and lack of confidence during pregnancy play no role in the development
      of coeliac disease in the offspring.

PMID- 12795463
TI  - Tumour necrosis factor alpha antibody affects gastrin release in Crohn disease.
AB  - BACKGROUND: Gastrin plays an important role in the regulation of gastric acid
      secretion in humans. Tumour necrosis factor alpha (TNF-alpha) stimulates gastrin
      release from antral G cells in vitro. The aim was to determine whether gastrin
      release decreases in patients with Crohn disease treated with monoclonal antibody
      to TNF-alpha. METHODS: Twenty-five consecutive patients with Crohn disease (10 M,
      15 F; 18 with fistulas) were treated with a single intravenous infusion of the
      monoclonal antibody to TNF-alpha, infliximab, at a dose of 5 mg/kg. Basal and
      bombesin stimulated gastrin was measured after an overnight fast immediately
      before and 2 weeks after infliximab. Helicobacter pylori status was determined by
      serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma
      gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS).
      Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59)
      pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in
      response to bombesin decreases in patients with Crohn disease treated with
      infliximab.

PMID- 12795465
TI  - Association of TNF-alpha-857C with inflammatory bowel disease in the Australian
      population.
AB  - BACKGROUND: It is now well established that susceptibility to inflammatory bowel
      disease is in part genetic, with one localization on chromosome 6 (IBD3) having
      been replicated in a number of populations. A candidate in that region, TNF
      alpha, contains polymorphisms in the promoter region that appear to be associated
      with disease. METHODS: More than 600 individuals from 170 multiplex IBD families
      were genotyped for four polymorphisms in the TNF-alpha gene and analysed for
      association. RESULTS AND CONCLUSION: A strong association was observed between
      transmission of the -857 C allele and disease. This effect was strongest in those
      families in which the NOD2 risk alleles are also segregating, supporting the
      existence of an interaction between IBD3 and IBD1 on chromosome 16.

PMID- 12795464
TI  - RDP58, a novel immunomodulatory peptide with anti-inflammatory effects. A
      pharmacological study in trinitrobenzene sulphonic acid colitis and Crohn
      disease.
AB  - BACKGROUND: Tumour necrosis factor (TNF) plays a key role in the pathogenesis of
      Crohn disease (CD). RDP58 is a novel anti-inflammatory decapeptide which was
      developed using a novel rational design strategy. Recently, RDP58 has proved to
      be a potent inhibitor of TNF production at a post-transcriptional step. The aims
      of this study were to investigate the anti-inflammatory properties of RDP58 ex
      vivo in human CD and in vivo in an experimental model colitis. METHODS: Biopsies
      and lamina propria mononuclear cells from inflamed colonic mucosa of 18 CD
      patients were cultured for 24 h in the presence or absence of RDP58. TNF was
      quantified in a bioassay: interferon (IFN)-gamma and interleukin (IL)-1beta
      levels were measured by enzyme-linked immunosorbent assays. Colitis was induced
      by intra-rectal administration of 2, 4, 6 trinitrobenzene sulphonic acid (TNBS)
      in rats. Inflammation was assessed following 7 days of oral therapy with RDP58 or
      vehicle alone. RESULTS: RDP58 led to decreased TNF and IFN-gamma (but not IL
      1beta) production by biopsies and lamina propria mononuclear cells from CD
      patients. In rats with TNBS-induced colitis, oral RDP58 therapy reduced weight
      loss and diarrhoea and improved macroscopic and histological inflammation scores.
      CONCLUSIONS: Our results suggest that RDP58 may be an effective therapy for CD
      with the clinical advantage of an oral administration.

PMID- 12795466
TI  - Oral prednisolone metasulphobenzoate in the treatment of active ulcerative
      colitis.
AB  - BACKGROUND: Corticosteroids are one of the mainstays of treatment for active
      ulcerative colitis, but they are associated with numerous side effects. The
      sparingly absorbed corticosteroid prednisolone metasulphobenzoate is used
      topically in the treatment of distal disease. A targeted-release oral preparation
      (Predocol) has been developed to allow delivery of this drug to the whole colon.
      We have studied the effect of oral Predocol on inflammation as measured by
      99Tc(m)-HMPAO leucocyte scintigraphy in patients with symptomatic and
      sigmoidoscopic relapse of known extensive ulcerative colitis. METHODS: Fourteen
      patients were recruited and received Predocol 47.1 mg twice daily, 8 for 7 days
      and 6 for 14 days. Scintigraphy was performed prior to and at the end of
      treatment. Each segment of colon was graded (0-4) and individual scores summed to
      give a total scintigraphic score. RESULTS: Total scintigraphic score improved by
      a mean of 2.5 (P = 0.027). Mean individual scores improved in the rectum by 0.7
      (P = 0.038) and in the descending colon by 0.8 (P = 0.033). CONCLUSIONS: Predocol
      is an oral preparation of a poorly absorbed salt of prednisolone that is
      effective in reducing inflammation over short treatment periods in patients with
      active ulcerative colitis.

PMID- 12795467
TI  - The C/C(-13910) and G/G(-22018) genotypes for adult-type hypolactasia are not
      associated with inflammatory bowel disease.
AB  - BACKGROUND: Lactose intolerance with adult-onset is due to the inadequate
      enzymatic activity of lactasephlorizin hydrolase (LPH). It is frequently seen in
      patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA
      genotypes, C/C(-13910) and G/G(-22018), located upstream from the LCT locus, the
      gene encoding for LPH, were recently identified as representing genetic markers
      for lactose intolerance. We utilized these two DNA genotypes to study their role
      in inflammatory bowel disease. METHODS: We investigated the prevalence of these
      two DNA variants using specific restriction enzyme digest assays in 166 patients
      with Crohn disease, in 120 healthy first-degree relatives of Crohn disease
      patients, in 63 patients with ulcerative colitis and in 187 healthy individuals.
      RESULTS: The analysis revealed a frequency of 21.4% of the 2 genotypes for adult
      type hypolactasia in our studied German cohort of healthy individuals, which is
      higher than previously reported (15%) based on the hydrogen (H2) breath test.
      This might indicate a higher sensitivity of genotyping, but it has to be
      confirmed in larger cohorts. No significant difference was detectable in the
      frequency of the C/C(-13910) and G/G(-22018) genotypes in patients with Crohn
      disease (C/C(-13910): 21.7%; G/G(-22018): 22.3%) compared to first-degree
      relatives (C/C(-13910): 21.7%; G/G(-22018): 20.8%), patients with ulcerative
      colitis (C/C(-13910): 20.3%; G/G(-22018): 20.3%) and healthy individuals (C/C(
      13910): 21.4%; G/G(-22018): 21.4%). CONCLUSION: The C/C(-13910) and G/G(-22018)
      genotype of adult-type hypolactasia is not associated with susceptibility to the
      pathogenesis of Crohn disease and ulcerative colitis.

PMID- 12795468
TI  - Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn
      disease.
AB  - BACKGROUND: Iron deficiency anaemia is a frequent complication of Crohn disease.
      Treatment with ferrous iron (Fe2-) compounds is often unsatisfactory and is
      associated with gastrointestinal side effects. Theoretically, oral iron
      supplementation may even be harmful, because iron may reinforce intestinal
      inflammation by catalysing production of reactive oxygen species. We investigated
      the effect of ferrous iron on disease activity and plasma antioxidant status in
      patients with active Crohn disease. METHODS: Ten patients with Crohn disease and
      iron deficiency and 10 healthy controls were given ferrous fumarate 120 mg for 7
      days. The Crohn Disease Activity Index, gastrointestinal complaints and blood
      samples for antioxidant status, anaemia, inflammation and iron absorption were
      investigated on day 1 and day 8. RESULTS: During 1 week of ferrous fumarate
      supplementation, the Crohn Disease Activity Index tended to increase (P = 0.071).
      Patients experienced aggravation of diarrhoea, abdominal pain and nausea. Plasma
      reduced cysteine was lower (P = 0.038) in patients than it was in controls. One
      week of ferrous iron supplementation further decreased reduced cysteine (P <
      0.001) and significantly decreased plasma-reduced glutathione (P = 0.004) in the
      patients. Serum iron increased significantly in patients after an oral iron load
      test (from 5.8 +/- 3.2 micromol/L to 30.9 +/- 13.1 micromol/L). CONCLUSIONS:
      Treatment of iron deficiency with ferrous fumarate deteriorated plasma
      antioxidant status and increased specific clinical symptoms in patients with
      active Crohn disease. Plasma reduced cysteine may be a sensitive indicator for
      oxidative stress in the intestine.

PMID- 12795469
TI  - Effects on cell proliferation, activator protein-1 and genotoxicity by fecal
      water from patients with colorectal adenomas.
AB  - BACKGROUND: The free water phase of feces (fecal water) may mediate the effects
      of diet on colon carcinogenesis. We examined the effects of fecal water from
      adenoma patients and controls on three parameters in colonocytes believed to be
      relevant to tumorigenesis, i.e. genotoxicity in intact cells and on isolated DNA,
      proliferative activity and activator protein-1 (AP-1) activity. METHODS:
      Genotoxicity in intact colonic cells was assayed using the single-cell gel
      electrophoresis assay ('comet' assay) and on isolated DNA using double-stranded
      DNA from the X-174 RF plasmid. Cell proliferation was assessed using the
      commercially available 'alamar blue' proliferation kit and AP-1 activity using
      cells transiently transfected with an AP-1-luciferase reporter construct.
      RESULTS: The data showed that lipid extracts of fecal water samples from the
      adenoma patients had a significantly higher capacity to induce cell proliferation
      than those from controls, and that this effect could be explained to a large
      extent by the concentrations of deoxycholic and chenodeoxycholic acids in the
      fecal water using regression models. No difference between patients and controls
      was observed for induction of AP-1 activity or induction of DNA strand breaks in
      intact cells. However, induction of DNA strand breaks in isolated DNA was
      significantly higher for the fecal waters from patients than for those from
      controls, which could be explained in part in a regression model by
      concentrations of lithocholic acid in fecal water and fecapentaene-12 in feces.
      CONCLUSIONS: Our results support the hypothesis that the biochemistry of fecal
      waters from adenoma patients and controls differs.

PMID- 12795470
TI  - Diagnosis of acute hepatitis C: anti-HCV or HCV-RNA?
AB  - BACKGROUND: In theory, the optimal method for diagnosing acute hepatitis C is
      nucleotide amplification. This is because of the significant delay in the
      emergence of hepatitis C virus (HCV) antibodies. We studied whether the use of
      HCV polymerase chain reaction (PCR) screening for acute HCV infection in a
      clinical setting would identify otherwise undetected cases. METHODS: Patients
      clinically suspected of having acute viral hepatitis were tested over a 32-month
      period (n = 2023). RESULTS: Sixty-four patients were found HCV ribonucleic acid
      (RNA) positive. Of these, 13 were suffering from an acute infection and 12 of
      these 13 patients were concomitantly anti-HCV (and HCV-RNA) positive at the time
      of diagnosis. One patient was HCV-RNA positive and anti-HCV negative. This
      symptom-free patient was tested because of known exposure to HCV 2 weeks
      previously. CONCLUSION: Anti-HCV is reliable in screening for acute hepatitis C.
      In cases of known/possible HCV exposure, we find that HCV PCR is the diagnostic
      of choice.

PMID- 12795472
TI  - Acute hepatitis induced by Greater Celandine (Chelidonium majus).
AB  - We report on two cases of acute liver injury along with the intake of Greater
      Celandine (Chelidonium majus), a well-known herbal remedy frequently used for
      irritable bowel syndrome. All other possible causes of acute liver damage were
      excluded in both patients. In one patient, cholestatic hepatitis recurred rapidly
      after involuntary re-exposition. Both patients fully recovered after the
      withdrawal of Greater Celandine. The two cases add to the existing database about
      the potential hepatotoxicity of drugs containing Greater Celandine and raise the
      question whether the approval of this drug should be re-evaluated in the light of
      lacking evidence for a therapeutic benefit.

PMID- 12795471
TI  - Increased arterial compliance in cirrhosis is related to decreased arterial C
      type natriuretic peptide, but not to atrial natriuretic peptide.
AB  - BACKGROUND: Increased arterial compliance (COMPart) has recently been described
      in patients with cirrhosis, particularly in advanced disease. The aim of the
      present study was to relate COMPart with arterial levels of the circulating
      natriuretic peptides: atrial natriuretic peptide (ANP) and C-type natriuretic
      peptide (CNP), both of which are vasodilators. METHODS: Thirty-one patients with
      cirrhosis, 14 non-cirrhotic patients with circulatory disturbances of the
      ischaemic and hypertensive type, and 10 healthy controls were investigated during
      a haemodynamic examination. RESULTS: The patients with cirrhosis showed the well
      known hyperdynamic circulation with elevated cardiac output, low arterial blood
      pressure, and reduced systemic vascular resistance. COMPart in the patients with
      cirrhosis (1.30 mL/mmHg) was significantly (P < 0.01) increased compared to that
      of non-cirrhotic patients (0.99 mL/mmHg) and controls (1.01 mL/mmHg). In the
      patients with cirrhosis, a significant inverse correlation was found between CNP
      and COMPart (r = -0.42, P < 0.01), but not between CNP and systemic vascular
      resistance (r = 0.31, P = 0.08). In the non-cirrhotic patients, CNP had a
      significant inverse correlation to COMPart (r = -0.68, P < 0.01) and a direct
      correlation to systemic vascular resistance (r = 0.62, P < 0.02). ANP was not
      significantly related to COMPart nor to systemic vascular resistance in any of
      the groups. CONCLUSION: The finding of an inverse relation between CNP and
      COMPart may suggest that a compensatory down-regulation of CNP occurs in patients
      with cirrhosis and other types of circulatory disorders when vasodilation
      persists. Regulation of large and small arteries by CNP may be different in
      cirrhosis. Arterial ANP is not related to properties of the large or small
      arteries.

PMID- 12795473
TI  - Idiopathic thrombocytopenic purpura and Helicobacter pylori infection.

PMID- 12795474
TI  - Intractable hepatic encephalopathy after tips with polytetrafluoroethylene
      covered stent-graft.

PMID- 12795475
TI  - Task-set reconfiguration with predictable and unpredictable task switches.
AB  - Participants switched frequently between high/low and odd/even classification of
      a digit. The interval between a task cue and the next digit varied between
      blocks. In Experiment 1, the task switched predictably every two, four, or eight
      trials. In Experiment 2, switching predictably every four trials was compared
      with random switching. With predictable switching, the cost was limited to the
      first trial of a run. Random switching produced a more gradual approach to
      asymptotic performance. After one performance, control processes attenuate the
      resulting change in task-set bias if a further switch is likely, but this
      strategic modulation is soon overwhelmed by task-set priming through further
      performances. Preparation reduced switch costs but not interference from the
      irrelevant attribute: Control of interference appears to be reactive, not
      proactive. Switch costs did not increase with run length, suggesting that
      retrieval of the task set last associated with the stimulus did not contribute to
      switch costs.

PMID- 12795476
TI  - Automatic vigilance for task-related information: perseverance after failure and
      inhibition after success.
AB  - In three experiments, the influence of failure and success on persistent
      automatic vigilance task-related information was investigated. Participants first
      had to work on a series of synonym selection problems for which negative and
      positive feedback was given independently of their performance. In the second
      part of the experiments, words from the synonym selection problems were presented
      as distractors in a dual task with speeded responses. Interference effects of the
      distractors served as a measure of automatic vigilance for the previous synonym
      selection problems that was unbiased by strategic processes. Interference effects
      were stronger for words from failure tasks than for words from success tasks.
      Comparing the success and failure conditions against a neutral baseline suggested
      that this difference was due to both a perseverance of automatic vigilance for
      failure tasks and an inhibition of cognitive accessibility after success.

PMID- 12795477
TI  - On the role of stimulus-response and stimulus-stimulus compatibility in the
      Stroop effect.
AB  - Stroop effects might be due to differences in stimulus-response compatibility
      (SRC) and/or to differences in stimulus-stimulus compatibility (SSC). Recent
      evidence for the role of SSC is inconclusive, because there were no controls for
      effects of SRC that are based on short-term associations between stimuli and
      responses (i.e., associations set up as the result of task instructions). In two
      experiments, SRC effects were controlled for. Regardless of whether the
      irrelevant and the relevant stimulus features were separated (Experiment 1) or
      integrated in one stimulus (Experiment 2), the results revealed an effect of SSC
      and an effect of SRC that was based on short-term associations. The results thus
      confirm that both processes at the level of encoding and processes at the level
      of response selection contribute to the Stroop effect.

PMID- 12795478
TI  - Semantic processing of Arabic, Kanji, and Kana numbers: evidence from
      interference in physical and numerical size judgments.
AB  - Two experiments were conducted with the following objectives (1) to replicate the
      finding of similar semantic representation of Arabic and written-word (Kanji and
      Kana) numbers with a direct numerical task, (2) to investigate the automatic
      semantic processing of Arabic and written-word numbers, and (3) to verify whether
      the assumption of a common semantic representation is valid in an indirect
      numerical task. Subjects were asked to judge which of two numbers (e.g, 6-8) was
      larger either in its numerical size (Experiment 1) or in its physical size
      (Experiment 2) using the three notations. Effects of two factors were analyzed:
      the congruity between numerical and physical size and the numerical distance. The
      effects of these factors were very similar across the three notations in
      Experiment 1, but were drastically different in Experiment 2. The results of
      Experiment 2 demonstrated the nonsemantic processing of Kana numbers, and suggest
      that there may be separate semantic representations for Arabic and Kanji numbers.

PMID- 12795479
TI  - Negative priming and stimulus familiarity: what causes opposite results?
AB  - There has been a discrepancy among past studies with regard to the relation
      between negative priming and familiarity of stimuli. That is, Malley and Strayer
      (1995; Strayer & Grison, 1999) reported that the more familiar the stimuli were,
      the larger negative priming became (i.e., a positive correlation), whereas
      DeSchepper and Treisman (1996; Treisman & DeSchepper, 1996) reported that the
      less familiar the stimuli were, the larger negative priming became (i.e., a
      negative correlation). These studies differ not only in their experimental tasks
      (identification vs. matching) but also in their respective manners of arranging
      unfamiliar stimuli (pure vs. mixed). In the present study, using an identical set
      of stimuli, we examined whether these factors caused the opposite results. An
      identification task with a pure arrangement produced a positive correlation, and
      a matching task with a mixed arrangement produced a negative correlation. These
      results suggest that the past opposing results are both replicable and that they
      have reflected the different causal mechanisms of negative priming.

PMID- 12795480
TI  - The effects of study-task relevance on perceptual repetition priming.
AB  - Repetition priming is easily elicited in many traditional paradigms, and the
      possibility that perceptual priming may be other than an automatic consequence of
      perception has received little consideration. This issue is explored in two
      experiments. In Experiment 1, participants named the target from a four-item
      category search study task more quickly than the nontarget study items at a later
      naming test. Experiment 2 extended this finding to conditions in which stimuli
      were individually presented at study. In three different study tasks, stimuli
      relevant to study-task completion elicited priming on a later test, but stimuli
      presented outside the context of a task did not. In both experiments, recognition
      was above chance for nonrelevant stimuli, suggesting that participants explicitly
      remembered stimuli that did not elicit priming. Results suggest that priming is
      sensitive to study-task demands and may reflect a more adaptive and flexible
      mechanism for modification of perceptual processing than previously appreciated.

PMID- 12795481
TI  - Conceptual processing effects on automatic memory.
AB  - In the present study, influences of conceptual processing on automatic forms of
      memory were investigated, using a category production task. The experiment
      employed Jacoby's (1991) process dissociation procedure and fits of multinomial
      models to estimate conscious and automatic memory for semantic and graphemic
      study tasks. Memory estimates from a generate-source model indicated more
      automatic memory for semantic than for graphemic items on the category production
      task. These results provide support for conceptual processing influences on
      automatic forms of memory.

PMID- 12795482
TI  - Long-term semantic transfer: an overlapping-operations account.
AB  - Semantic priming is usually a short-lived effect. However, it is also usually
      investigated using undemanding tasks, such as naming or lexical decision. We
      instead required subjects to perform category verification. We observed
      semantically mediated transfer occurring at an average lag of 90 intervening
      trials. We also observed that this priming was specific to the stimulus
      properties made salient in prime and probe displays and the particular task
      demanded in those displays. We interpret the results within an overlapping
      operations framework, based on the work of Kolers (e.g., 1976).

PMID- 12795483
TI  - Memory for actions: self-performed tasks and the reenactment effect.
AB  - Encoding action phrases by enactment (self-performed tasks, or SPTs) leads to
      better memory than does observing actions (experimenter-performed tasks, or EPTs)
      or hearing action phrases (Engelkamp, 1998). In addition, recognition memory for
      SPTs is enhanced when test items are reenacted. Experiment 1 demonstrated a
      reenactment effect for EPTs, as well as for SPTs, indicating that the effect can
      be based on visual, as well as motoric, feedback. However, the reenactment effect
      in SPTs was found even when the participants were blindfolded at test (Experiment
      2), indicating that the basis for the reenactment effect differs across SPTs and
      EPTs. Experiments 3 and 4 provided additional evidence that visual feedback is
      not critical for reenactment recognition in the case of SPTs. In addition, these
      experiments failed to show a hand congruency effect (enhanced recognition when
      the same hand enacts at study and at test), indicating that this effect is not as
      generalizable as the reenactment effect. These results have important
      implications for the motor-encoding hypothesis of the enactment effect.

PMID- 12795484
TI  - Remembering chosen and assigned options.
AB  - Recent studies have shown systematic choice-supportive memory for past choices,
      wherein people tend to overattribute positive features to options they chose and
      negative features to unchosen options (Mather & Johnson, 2000, Mather, Shafir, &
      Johnson, 2000). In contrast, the present experiments showed no choice-supportive
      memory bias for assigned options. Rather than having a general motivation to
      recall the chosen or the assigned option in a more positive light, people appear
      to be influenced by heuristics that vary with context: In recalling past choices,
      people expect the chosen option to contain more positive and fewer negative
      features than do its competitors. In recalling past assignments, in contrast,
      people expect the assigned option to be remembered better than the unassigned
      alternatives. This vividness heuristic leads to systematic misattribution of new
      features to unassigned alternatives, but not in a manner supportive of the
      assigned option. Some implications of these findings are discussed.

PMID- 12795485
TI  - Migration of objects and inferences across episodes.
AB  - Participants viewed episodes in the form of a series of photographs portraying
      ordinary routines (e.g., eating at a restaurant) and later received a recognition
      test. In Experiment 1, it was shown that objects (e.g., a vase of flowers, a
      pewter lantern) that appeared in a single episode during the study phase migrated
      between memories of episodes described by the same abstract schema (e.g., from
      Restaurant Episode A at study to Restaurant Episode B at test), and not between
      episodes anchored by different schemas. In Experiment 2, it was demonstrated that
      backward causal inferences from one study episode influenced memories of other
      episodes described by the same schema, and that high-schema-relevant items viewed
      in one episode were sometimes remembered as having occurred in another episode of
      the same schematic type.

PMID- 12795486
TI  - "If I didn't write it, why would I remember it?" Effects of encoding, attention,
      and practice on accurate and false memory.
AB  - In two experiments involving recall and recognition, we manipulated encoding
      strategies, attention, and practice in the Deese, Roediger, and McDermott false
      memory procedure. During the study of auditory word lists, participants listened
      to the words, wrote the words, wrote the second letter of the words, or counted
      backward by threes and wrote numbers in time with the words. The results from
      both experiments showed that, relative to the full-attention hear word condition,
      the divided-attention write number condition impaired accurate memory, but not
      false memory. In contrast, the focused-attention write word and write second
      letter conditions were comparable to the hear word condition in producing
      accurate memory, yet they were better at reducing false memory. But even after
      multiple study-test trials, people still falsely recalled or recognized words
      that they had never written during study. These results are consistent with
      predictions generated from fuzzy trace theory and the activation/monitoring
      framework.

PMID- 12795487
TI  - Roles of working memory capacity and long-term working memory skill in complex
      task performance.
AB  - In the present research, we examined the relative roles of domain-general and
      domain-specific individual difference characteristics in complex cognitive task
      performance. Specifically, we examined the impact both of working memory (WM)
      capacity and of acquired skills used to encode presented information in an
      accessible form in long-term working memory (LTWM) on performance in a complex
      aviation task environment. Measures of WM capacity and LTWM skill served as
      performance predictors. A criterion measure of task performance was related to
      the predictor measures. The results indicated that an increase in LTWM skill
      decreases the role of WM capacity as the determinant of complex task performance,
      although both measures are important performance predictors. We discuss how the
      two distinct WM constructs coexist and interact to support complex task
      performance.

PMID- 12795488
TI  - On the generation and evaluation of inferences from single premises.
AB  - A theory of how individuals construct mental models to draw inferences from
      single premises was tested in three experiments. Experiment 1 confirmed a
      counterintuitive prediction that it is easier to generate inferences between
      conditionals and disjunctions than it is to evaluate them. Experiment 2
      replicated this finding, but an advantage found in the first experiment for
      conditional-to-disjunction over disjunction-to-conditional inferences was removed
      with different sentence contents. Experiment 3 showed that disjunction-to
      conditional inferences were facilitated when premises expressed familiar
      indicative relations, whereas conditional-to-disjunction inferences were
      facilitated when premises expressed causal relations. The results indicate that
      small changes in task format can have large effects on the strategies that people
      use to represent and reason about different sentential connectives. We discuss
      the potential for theories other than mental models to account for these results.
      We argue that, despite the important role played by single-premise inferences in
      paraphrasing logical forms during inference, mental logic theories cannot account
      for the results reported here.

PMID- 12795489
TI  - Locomotion, incidental learning, and the selection of spatial reference systems.
AB  - In three experiments, we examined the effects of locomotion and incidental
      learning on the formation of spatial memories. Participants learned the locations
      of objects in a room and then made judgments of relative direction, using their
      memories (e.g., "Imagine you are standing at the clock, facing the jar. Point to
      the book"). The experiments manipulated the number of headings experienced, the
      amount of interaction with the objects, and whether the participants were
      informed that their memories of the layout would be tested. When participants
      were required to maintain a constant body orientation during learning (Experiment
      1), they represented the layout in terms of a single reference direction parallel
      to that orientation. When they were allowed to move freely in the room
      (Experiment 2), they seemed to use two orthogonal reference axes aligned with the
      walls of the enclosing room. Extensive movement under incidental learning
      conditions (Experiment 3) yielded a mixture of these two encoding strategies
      across participants. There was no evidence that locomotion, interaction with
      objects, or incidental learning led to the formation of spatial memories that
      differed from those formed from static viewing.

PMID- 12795490
TI  - The effect of revised populations on mortality statistics for the United States,
      2000.
AB  - OBJECTIVES: This report presents revised mortality statistics for the year 2000
      based on April 1, 2000, population figures from the 2000 census. Death rates are
      presented by race, Hispanic origin, sex, age, and cause of death. Life
      expectancies are presented by race (white and black), sex, and age. The revised
      statistics are compared with previously published statistics that used July 1,
      2000, postcensal population estimates based on the 1990 census. METHODS: Data in
      this report are based on information from all death certificates filed in the 50
      States and the District of Columbia. The statistics presented in this report are
      computed on the basis of two sets of population figures provided by the U.S.
      Census Bureau. The first set includes July 1, 2000, postcensal population
      estimates based on the 1990 decennial census. The second set includes April 1,
      2000, populations from the 2000 decennial census bridged to single race
      categories. RESULTS: Crude death rates were lower for all groups using the April
      1, 2000, populations. Age-specific death rates were generally lower for most age
      groups, except for infants and the very old for which death rates were higher.
      Age-specific death rates for males were lower for most age groups, except infants
      and those 75 years and over. For females, with the exception of infants, age
      specific death rates were lower. Race-specific pattems by age for the white and
      black populations were similar to all races combined. For the American Indian
      population, age-specific death rates were substantially lower for ages under 75
      years. For ages 75 years and over, American Indian death rates were dramatically
      higher. Age-specific death rates for the Asian or Pacific Islander (API)
      population were higher for ages under 15 years; lower for ages 15-84 years,
      especially for the 15-34 year age group; and higher for those 85 years and over.
      For the Hispanic population, age-specific death rates were substantially lower
      for those age 15-34 years and higher for those age 55 years and over, especially
      for those age 85 years and over. For the total white and total black populations,
      the age-adjusted death rate was somewhat higher for males and lower for females.
      For API the pattern was reversed. For the American Indian and Hispanic
      populations, age-adjusted death rates were higher for both males and females. For
      the 15 leading causes of death, age-adjusted death rates based on the April 1,
      2000, population figures were lower for heart disease, cancer, chronic liver
      disease, septicemia, diabetes, chronic lower respiratory diseases, unintentional
      injuries, homicide, suicide, and hypertension. Age-adjusted death rates were
      higher for pneumonitis, Alzheimer's disease, and stroke. Rates were unchanged for
      influenza and pneumonia and nephritis, nephrotic syndrome and nephrosis. Life
      expectancy at birth was higher for the entire population and both the white and
      black populations using the April 1, 2000, population figures. It was 0.1 year
      higher for the whole population as well as for the total white and total black
      populations. For the total male population, life expectancy at birth was 0.1 year
      higher while it was 0.2 years higher for the female population. The increase in
      life expectancy at birth was 0.1 year for both sexes within the white and black
      populations. This observed gain in life expectancy at birth based on the revised
      population figures is reversed for life expectancy at the oldest age groups for
      the whole population and for males. A similar pattern is observed for both white
      and black males; however, the magnitude of the decline in life expectancy at
      older ages is much greater among black males. Among females of both race groups
      and the total population, there is either no change or an increase in life
      expectancy in the oldest age groups. CONCLUSIONS: Revised death rates and life
      expectancies are, in many cases, significantly different from previously
      published mortality statistics calculated using 1990-based postcensal estimates
      for 2000. Thus, previously published mortality statistics for 2000 using the 1990
      based populations will not be comparable to the corresponding statistics that
      will be published for 2001. The data in this report will provide comparable 2000
      data. Efforts are also underway to revise previously published mortality tables
      for 2000 as well as previously published data for 1991-99.

PMID- 12795491
TI  - At issue: predicting drug-free treatment response in acute psychosis from the
      Soteria project.
AB  - Although an estimated 25 to 40 percent of acute psychoses remit without
      antipsychotic drug treatment, only limited efforts have been made to identify
      individuals in early episodes who might be able to recover without medications.
      This retrospective exploratory study uses baseline information from the Soteria
      project (young, unmarried, first and second episode DSM-II schizophrenia, n =
      179) to develop a preliminary model for this purpose. Forty-three percent of
      experimentally treated subjects received no antipsychotic medications during the
      2-year followup period and were designated "drug-free responders." At followup,
      this group had better outcomes (+ 0.82 of a standard deviation [SD]) on a
      composite outcome scale (representing rehospitalization, psychopathology,
      independent living, social and occupational functioning). A predictive model
      using three variables (age, the Goldstein Adolescent Social Competence Scale
      score, and number of diagnostic symptoms) correctly identified this subgroup 79
      percent of the time (boot-strapped 95% confidence interval [CI], 65-90%).
      Predicted drug-free responders exhibited moderately better outcomes (effect size:
      0.38 to 0.61 of an SD) when treated at Soteria. These data advance the hypothesis
      that an identifiable subgroup of individuals with early episode psychosis might
      fare better when receiving specialized psychosocial intervention and minimal or
      no use of antipsychotic medications.

PMID- 12795492
TI  - Commentary on the Soteria project: misguided therapeutics.

PMID- 12795493
TI  - Cost-effectiveness of risperidone, olanzapine, and conventional antipsychotic
      medications.
AB  - To assess the cost and effectiveness of risperidone, olanzapine, and conventional
      antipsychotic medications under "usual practice" conditions in a large, public
      mental health system, 108 persons diagnosed with schizophrenia or schizoaffective
      disorder were randomly assigned to one of these three medication groups and
      followed prospectively over a 12-month period using standard instruments and
      procedures. Psychiatric medication costs increased more over time in both the
      olanzapine and risperidone groups than in the conventional medication group.
      Compliance with the prescribed medication was higher in the olanzapine group than
      in the conventional group. No differential effects by medication group were
      evident in this sample on the symptoms of schizophrenia, side effects,
      psychosocial functioning, time to discharge for index hospitalization, survival
      to initial rehospitalization, or client satisfaction with services. These results
      extend findings from previous efficacy and naturalistic studies in several ways
      but are limited chiefly by the small number of subjects who completed 6 to 12
      months of the clinical trial, and the resulting power to detect differences in
      the statistical analyses.

PMID- 12795494
TI  - Antipsychotic dosing and concurrent psychotropic treatments for Medicaid-insured
      individuals with schizophrenia.
AB  - Antipsychotic medications have been first line treatment for schizophrenia for
      half a century, yet few studies have assessed outpatient maintenance treatment in
      large populations. This article describes oral antipsychotic dosing patterns and
      psychotropic treatments using computerized Medicaid claims data for individuals
      who were diagnosed with schizophrenia and received treatment on an outpatient
      basis during 1991. The findings show that the mean daily oral antipsychotic dose
      was 729 +/- 586 chlorpromazine equivalents (CPZ-EQ) for high-potency agents and
      304 +/- 328 CPZ-EQ for low-potency agents. Males, younger individuals, and
      African-Americans received larger mean daily doses of high-potency agents,
      ranging from 747 to 800 CPZ-EQ. Antiparkinsonian agents were prescribed for over
      90 percent of the outpatient antipsychotic treatment exposure. In summary, young
      adults, males, and African-Americans were given high-potency antipsychotic
      medications at outpatient maintenance doses that exceeded the maximum recommended
      levels, despite well-established evidence that high-dose treatment offers no
      additional benefit. Likewise, concurrent antiparkinsonian treatment exceeded the
      1990 World Health Organization recommendations.

PMID- 12795495
TI  - Estimating the costs and benefits of new drug therapies: atypical antipsychotic
      drugs for schizophrenia.
AB  - This article presents an analytic tool populated with data from published studies
      to illustrate the likely impacts of a switch from typical to atypical
      antipsychotic drugs over a 3-year period on individual, family, and societal
      outcomes for a U.S. schizophrenia population. Data taken from clinical trials and
      observational data studies are used. Changes in annual health care costs,
      schizophrenia symptom days, extrapyramidal symptom (EPS) days, suicide rates, and
      employment days are estimated. For each 1,000 people treated with typical drugs,
      the base case scenario gives estimates of annual medical care costs of dollar
      28.9 million with 80,253 moderate/severe schizophrenia symptom days and 92,006
      EPS days. In the base case scenario, after switching to atypical drugs,
      schizophrenia symptom days are estimated to decrease up to 33 percent, EPS days
      up to 50 percent, and total medical care costs up to 19 percent over the 3-year
      period. Suicide rates fall and employment rates increase. The direction of the
      impacts remain the same for a wide range of input parameter values used in
      sensitivity analyses. Thus, switching to atypical drugs will likely reduce total
      medical care costs and decrease other disease burdens for people with
      schizophrenia, their families, and society.

PMID- 12795496
TI  - Comorbid substance use reduces the health care contacts of suicide attempters
      with schizophrenia spectrum or mood disorders.
AB  - Utilization of health care services has been found to differ between psychiatric
      disorders. However, the pattern of health care contacts among suicide attempters
      with mental disorders is not known. This study systematically investigated the
      pattern of health care contacts among suicide attempters with schizophrenia
      spectrum versus mood disorders with or without comorbid substance use disorders
      both before and after attempted suicide. All consecutive medically treated
      suicide attempters in Helsinki from January 15, 1997, to January 14, 1998, were
      identified (n = 1,198). Data were gathered on all their health care contacts
      within the 12 months before and after the index attempt. Whereas the clear
      majority of all suicide attempters with schizophrenia spectrum or mood disorders
      had a treatment contact during the 30 days following the attempt, half of those
      with pure substance use disorders were without any contact with health care.
      Comorbid substance use made treatment less likely after attempted suicide among
      both psychiatric disorder groups; those with schizophrenia spectrum and comorbid
      substance use disorders were seven times more often left without aftercare
      recommendation than those without substance use comorbidity. Comorbid substance
      use disorders among suicide attempters with schizophrenia spectrum disorders
      decrease the likelihood of active aftercare, despite high suicide risk.

PMID- 12795497
TI  - A multivariate prediction model of schizophrenia.
AB  - Univariate prediction models of schizophrenia may be adequate for hypothesis
      testing but are narrowly focused and limited in predictive efficacy. Therefore,
      we used a multivariate design to maximize the prediction of schizophrenia from
      premorbid measures and to evaluate the relative importance of various predictors.
      Two hundred twelve Danish subjects with at least one parent diagnosed in the
      schizophrenia spectrum (high risk) and 99 matched subjects with no such parent
      (low risk) were assessed on 25 premorbid variables in seven domains (genetic
      risk, birth factors, autonomic responsiveness, cognitive functioning, rearing
      environment, personality, and school behavior) when the subjects averaged 15
      years of age. Twenty-five years later, 33 subjects had received lifetime
      diagnoses of schizophrenia. Discriminant function analyses were used to
      discriminate schizophrenia outcomes from no mental illness and nonschizophrenia
      outcomes on the basis of premorbid measures. Regardless of the comparison group
      used, schizophrenia was predicted by the interaction of genetic risk with rearing
      environment, and disruptive school behavior. Within the high-risk group, two
      thirds of schizophrenia outcomes were correctly predicted by these premorbid
      measures; three-quarters of those with no mental illness were also correctly
      predicted. Prediction was enhanced among those with two schizophrenia spectrum
      parents, lending support to a multiplicative gene x environment model.
      Implications for early identification/primary prevention efforts are discussed.

PMID- 12795499
TI  - Further evidence that congenital dermatoglyphic abnormalities are associated with
      psychosis: a twin study.
AB  - The presence of abnormal palmar flexion creases (APFC) and dermatoglyphic ridge
      dissociation (RD) may constitute enduring evidence of a prenatal insult that
      occurred before the third trimester of intrauterine life. We examined these
      dermatoglyphic abnormalities in a twin study of psychotic disorders. RD and APFC
      were analyzed in a monozygotic (MZ) twin sample from the Maudsley Hospital in
      London (11 normal control pairs, 16 pairs concordant for psychosis, 9 pairs
      discordant for psychosis, 1 concordant triplet, and 1 triplet with one affected
      member). The risk of either RD or APFC was 44 percent in affected twins and 20
      percent in nonaffected twins (odds ratio = 3.25, 95% confidence interval: 1.03
      10.31; one-sided p = 0.023). In the group of MZ twins discordant for psychosis,
      discordance for RD or APFC always paralleled discordance for psychosis (one-sided
      p = 0.078), suggesting the operation of nongenetic factors. The results confirm
      previous work suggesting the possibility that nongenetic factors early in
      pregnancy contribute to the liability to develop psychosis in later life.

PMID- 12795498
TI  - The Lifetime Dimensions of Psychosis Scale (LDPS): description and interrater
      reliability.
AB  - A new rating scale, the Lifetime Dimensions of Psychosis Scale (LDPS), is
      described. The LDPS creates a profile of the lifetime characteristics of each
      case based on retrospective ratings, encompassing the positive, bizarre,
      negative, and disorganized symptom factors identified by previous studies of
      psychotic disorders, plus mood-related symptomatology, degree of deterioration,
      and complicating factors over the course of illness. A preliminary 39-item scale
      and instruction manual were developed. Intraclass correlation coefficients (ICCs)
      for positive symptom and mood item total scores were 0.76 to 0.87 (mean of 0.70
      for all items). Highly intercorrelated (tau-b coefficients) or unreliable items
      were eliminated to create the final 20-item version 2. Good-excellent reliability
      was observed in a second study using different raters. The LDPS is designed for
      use by experienced clinicians or researchers who have access to comprehensive
      clinical information, including semistructured diagnostic interviews, psychiatric
      records, and family history reports. Dimensional scores and multidimensional
      patterns might prove useful in studying the relationship of clinical phenotype to
      genotypes, treatment response, and other variables. They may also be useful in
      clinical practice.

PMID- 12795500
TI  - Characteristics of Korean-Americans with schizophrenia: a cross-ethnic comparison
      with African-Americans, Latinos, and Euro-Americans.
AB  - The purpose of this study was (1) to identify the demographic and psychosocial
      characteristics of Korean-Americans with schizophrenia, and (2) to compare the
      demographic and psychosocial characteristics of Korean-Americans with
      schizophrenia to African-American, Latino, and Euro-American individuals with
      schizophrenia. Based on current models of psychosocial functioning in
      schizophrenia, four dimensions--clinical status, functional status, subjective
      experience, and community risk--were examined and compared across the ethnic
      groups. Data on 223 individuals diagnosed with schizophrenia who were Korean
      American (n = 40), Euro-American (n = 95), African-American (n = 60), and Latino
      (n = 28) were gathered in face-to-face interviews. All of the subjects were
      engaged in outpatient treatment. After controlling for sociodemographic
      variables, the main findings were as follows: (1) while the Korean-Americans were
      the least acculturated, their symptom levels and clinical status were highly
      comparable with those of the other ethnic groups; (2) based on living situation,
      family contact, social functioning, activities of daily living, and vocational
      data, the Korean-Americans showed a stronger familial orientation, lower social
      initiation, and higher affiliative qualities than other groups; (3) the Korean
      American sample had comparable levels of self-esteem but reported lower
      satisfaction with life than the other ethnic groups. Minority status did not
      confound these findings. It is concluded that the psychosocial profile of the
      Korean-Americans was strongly influenced by their traditional and collectivistic
      cultural orientation. At the same time, the lower levels of life satisfaction
      could indicate that they experience difficulties in adjusting to Western society.
      Considering the Korean-Americans' strong tendency to maintain a collectivistic
      cultural orientation, mental health services need to be congruent with their
      cultural expectations. Interventions should also identify risk factors associated
      with lower life satisfaction. Several research implications are discussed.

PMID- 12795501
TI  - Are communication deviance and expressed emotion related to family history of
      psychiatric disorders in schizophrenia?
AB  - Studies have reported that certain measures of intrafamilial transactions are
      associated with an increased risk both for the initial onset of schizophrenia and
      for its recurrence following the initial episode of disorder. Two of the most
      studied of these are communication deviance (CD), a measure of subclinical
      thought disorder expressed in speech, and expressed emotion (EE), defined as
      notable attitudes of criticism and/or emotional overinvolvement manifested in a
      semistructured interview. A previous study (Goldstein et al. 1992) examined
      whether these two measures were associated with the presence of a diagnosable
      psychiatric disorder in the biological parents of recent-onset schizophrenia
      patients. In general, they were not. The present study went one step further. It
      examined whether these same measures were correlated with family history of
      schizophrenia or affective disorder in the biological parents and siblings of
      these same parents. High EE was not associated with a greater family history of
      schizophrenia spectrum disorders among the parent's parents and siblings but was
      unexpectedly found to be inversely associated with familial affective disorders.
      In contrast, CD was associated with a family history of schizophrenia spectrum
      disorders among the parent's parents and siblings. The findings are consistent
      with the possibility that CD may be an indicator of a genetic vulnerability
      factor for schizophrenia.

PMID- 12795502
TI  - Familial expressed emotion: outcome and course of Israeli patients with
      schizophrenia.
AB  - We investigated the validity of expressed emotion (EE) in Israel. The study
      sample consisted of 108 patients with schizophrenia and 15 with schizoaffective
      disorder, and their key relatives. EE was rated with the Five Minute Speech
      Sample (FMSS). Patient households were categorized by EE and its two components:
      criticism and emotional overinvolvement. Patients were rated with the Brief
      Psychiatric Rating Scale (BPRS) at admission, at discharge, and 6 months after
      discharge. Readmissions were determined over a 9-month period. High EE and
      particularly high criticism were significantly associated with poorer outcome
      (higher rate of and earlier readmissions, and higher BPRS score at followup) and
      worse illness course (higher annual number of prior psychiatric hospital
      admissions). Odds ratios between high EE and high criticism and readmission were
      2.6 and 3.5, respectively. The strongest predictor of earlier readmission was the
      interaction of high criticism x poor compliance with medication. The results
      converge to further confirm the notion that familial EE is a valid crosscultural
      predictor of the clinical course of schizophrenia. Moreover, EE has predictive
      power in very chronic samples. Criticism appears to be the crucial EE component
      linked with short-term outcome. Treatment aimed at reducing high criticism is
      warranted. The FMSS appears to have predictive validity.

PMID- 12795503
TI  - Graduate student in peril: a first person account of schizophrenia.

PMID- 12795505
TI  - A bereavement model for the intensive care nursery.
AB  - The death of an infant in a neonatal intensive care unit presents unique
      challenges to the infant's family and caregivers. The grieving process may begin
      before the infant is born and continue for months, even years, after the death.
      Parents and families often feel isolated as they grieve the loss of a child whom
      few other people knew. Caregivers may also feel overwhelmed during this time, as
      they seek to provide decedent care in a sensitive way that will be helpful to the
      family while grieving themselves. Recognizing the needs of the families and
      caregivers, the Duke University Medical Center Intensive Care Nursery developed a
      bereavement program that provides education and assistance to the intensive care
      nursery staff, who care for the family at the time of death and provide follow-up
      for the family for up to one year after the death as they grieve the loss of
      their infant.

PMID- 12795504
TI  - The neonatal liver: Part III: Pathophysiology of liver dysfunction.
AB  - The liver, the largest organ in the body, is critical to a number of key
      metabolic functions. Its also plays an important role in removing the waste
      products of metabolism (particularly ammonia) and in detoxifying drugs and other
      substances such as endogenous hormones and steroid compounds. In addition, the
      liver plays a major role in the production of clotting factors, plasma proteins,
      bile salts, and bilirubin. Many neonates display signs of hepatic dysfunction
      such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. These often
      occur secondary to systemic illness, such as sepsis or hypoxic injury, or
      following the use of drugs or parenteral nutrition to treat other problems.
      Although rare, primary liver disease does occur in neonates and must be
      recognized promptly, with treatment initiated in a timely manner to prevent
      unnecessary sequelae. This article, the third in a series on the liver, examines
      causes of liver dysfunction in neonates, beginning with an overview of jaundice
      and hepatomegaly and moving to a discussion of specific diseases.

PMID- 12795506
TI  - Cognitive outcomes in school-age children born prematurely.
AB  - The purpose of this article is to discuss findings in the literature regarding
      long-term developmental outcomes of infants born prematurely, to examine
      potential causes of individual differences in these outcomes, and to explore
      directions for future research. An extensive table summarizes recent (1996-2002)
      international studies of developmental outcomes among children of school age and
      older who were born with low birth weight, especially as the studies relate to
      cognitive development and academic performance. The discussion then examines how
      characteristics of the child and the environment may interact to produce
      individual differences in outcomes. Processes of attention regulation within the
      context of the psychosocial environment are examined as an important possible
      direction for future research. When designing and implementing interventions
      aimed at improving outcomes in this and other groups of children at risk for
      delays and deficits, it is important to consider how various factors affect
      development.

PMID- 12795507
TI  - Premature infant massage in the NICU.
AB  - Infant massage therapy is an inexpensive tool that should be utilized as part of
      the developmental care of the preterm infant. Nurses have been hesitant to begin
      massage therapy for fear of overstimulating the infant and because there has been
      insufficient research to prove its safety. Recent research, however, has shown
      that the significant benefits of infant massage therapy far outweigh the minimal
      risks. When infant massage therapy is properly applied to preterm infants, they
      respond with increased weight gains, improved developmental scores, and earlier
      discharge from the hospital. Parents of the preterm infant also benefit because
      infant massage enhances bonding with their child and increases confidence in
      their parenting skills. This article discusses the benefits and risks of massage
      for preterm infants and their families and explains how to implement massage
      therapy in the neonatal intensive care setting.

PMID- 12795508
TI  - Partnerships between mothers and professionals.

PMID- 12795509
TI  - Fetal alcohol syndrome.

PMID- 12795510
TI  - VATER Association.
AB  - Baby S began oral feedings on day 8 at 20 ml/kg/day. The infant reached full
      enteral feedings on day 11 and was subsequently advanced to an ad lib demand
      schedule. The broviac catheter was removed on day 13. An orthopedic surgeon was
      consulted to evaluate abnormalities of the upper extremities and hip laxity noted
      on admission examination. The orthopedic specialist found decreased abduction of
      the hips bilaterally with no instability and normal range of motion on exam. An
      ultrasound showed bilateral posterior subluxation with no frank dislocation. The
      infant was evaluated by a physical therapist and received daily splinting and
      stretching of the upper extremities, with continued evaluation planned following
      discharge. When the infant was discharged on day 15, she was breastfeeding on a
      demand schedule with bottle supplementation and continued to receive ranitidine
      and metoclopramide. Follow-up was scheduled with the cardiologist, the orthopedic
      surgeon, and the family physician.

PMID- 12795511
TI  - Electrodiagnostic approach to patients with weakness.
AB  - Electrodiagnosis has a key role in the evaluation of patients presenting with
      weakness. The electrodiagnostician should maintain a broad inclusive differential
      diagnosis and tailor the examination using a sound conceptual framework. A clear
      understanding of what is normal provides the proper foundation upon which to
      judge electrodiagnostic findings. Many peripheral neuromuscular conditions
      manifest themselves in characteristic ways on NEE and nerve conduction testing,
      making them identifiable to the skilled electrodiagnostic medicine consultant.

PMID- 12795512
TI  - Repetitive nerve stimulation and exercise testing.
AB  - Repetitive nerve stimulation and exercise testing are useful in the evaluation of
      patients with suspected disorders of the NMJ and muscle membrane excitability
      when performed with close attention to technical factors. They can be very
      helpful in the diagnosis of myasthenia gravis. Lambert-Eaton myasthenic syndrome,
      and botulism, as well as rare disorders of skeletal muscle membrane excitability,
      including paramyotonia congenita, myotonia congenita, myotonic dystrophy, and the
      periodic paralyses.

PMID- 12795513
TI  - Single-fiber electromyography.
AB  - Single-fiber EMG is a technique introduced in 1963 by Stalberg and Ekstedt for
      recording single muscle fiber action potentials by means of a specially
      constructed needle with a 25-microm recording surface. The needle is positioned
      in the muscle to record from two or more time-locked potentials belonging to the
      same motor unit. Jitter is the variability in the arrival time of action
      potentials to the recording electrode between consecutive discharges. This
      variability reflects end-plate conduction and is measured along with fiber
      density, which is the average number of fibers belonging to the same motor unit
      that is in the recording area. An abnormal test is one in which more than 10%, or
      the mean, of 20 fiber pairs has increased jitter when compared with normal
      reference values. Increased fiber density is seen with reinnervation. Single
      fiber EMG is more sensitive than conventional EMG and is the most sensitive, but
      not specific, test for myasthenia gravis. Lambert-Eaton myasthenic syndrome, and
      other neuromusculasr junction pathology. It has been useful in the evaluation of
      some neuropathies and myopathies and has provided valuable information on the
      motor unit spatial arrangement, territory, microphysiology, and pathophysiology.

PMID- 12795514
TI  - Quantitative electromyography.
AB  - Quantitative EMG is an MUAP analysis technique providing objective information on
      the NEE. The concept and techniques are not new; however, with the advancement of
      computer technology, quantitative EMG is now more easily performed. The study
      requires solid knowledge of basic neurophysiology and access to the appropriate
      instrument to provide smooth technique and accurate interpretation. Despite
      recent technical advances, the original MUAP parameters defined by Buchthal are
      still widely used today as reference values. It is increasingly recognized that
      many factors can influence the obtained parameters. The ability to measure
      something does not mean that it is fully understood. The future of quantitative
      EMG will depend on increased understanding of the physiologic and
      pathophysiologic significance of the detailed numeric parameters that are
      generated.

PMID- 12795515
TI  - Motor unit number estimation.
AB  - Since its introduction 30 years ago, MUNE techniques have increasingly been
      refined and applied to a wide variety of neuromuscular disorders. Differences of
      opinion remain among MUNE investigators as to which method is best; however,
      statistical and MPS MUNE are currently the most widely used. Numerous
      methodologic issues remain, including the development of detailed universal
      standards for each technique and the implementation of modifications for the
      enhancement of reproducibility. These issues are the subjects of ongoing
      investigation. Despite technical variability, the MUNE values obtained using
      different methods show good agreement in studies of normal subjects and in
      patients with a variety of neurogenic processes. MUNE has been applied most
      successfully to patients with amyotrophic lateral sclerosis and to animal models
      of motor neuron disease, providing significant insight into the pathophysiology
      of these disorders. These techniques are increasingly being incorporated into
      clinical therapeutic trials. MUNE offers promise in the study of neuromuscular
      disease, enabling the collection of novel data in the living patient unobtainable
      by any other method.

PMID- 12795516
TI  - Quantitative sensory testing.
AB  - Quantitative sensory testing is a reliable way of assessing large and small
      sensory nerve fiber function. Sensory deficits may be quantified and the data
      used in parametric statistical analysis in research studies and drug trials. It
      is an important addition to the neurophysiologic armamentarium, because
      conventional sensory nerve conduction tests only the large fibers. QST is a
      psychophysical test and lacks the objectivity of NCS. The results are subject to
      changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion.
      When patients are consciously or unconsciously biased toward an abnormal QST
      result, no psychophysical testing can reliably distinguish these patients from
      those with organic disease. QST tests the integrity of the entire sensory
      neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or
      central nervous system may give rise to abnormalities in QST. As is true for
      other neurophysiologic tests, QST results should always be interpreted in light
      of the patient's clinical presentation. Quantitative sensory testing has been
      shown to be reasonably reproducible over a period of days or weeks in normal
      subjects. Because longitudinal QST studies of patients in drug trials are usually
      performed over a period of several months to a few years, reproducibility studies
      on the placebo-control group should be included. For individual patients, more
      studies are needed to determine the maximum allowable difference between two QSTs
      that can be attributed to experimental error. The reproducibility of thermal
      thresholds may not be as good as that of vibration threshold. Different
      commercially available QST instruments have different specifications (thermode
      size, stimulus characteristics), testing protocols, algorithms, and normal
      values. Only QST instruments and their corresponding methodologies that have been
      shown to be reproducible should be used for research and patient care. The data
      in the literature do not allow conclusions regarding the superiority of any QST
      instruments. The future of QST is promising; however, many factors can affect QST
      results. As is true for other neurophysiologic tests, QST is susceptible to many
      extraneous factors and to misuse when not properly interpreted by the clinician.

PMID- 12795517
TI  - Evaluation of the autonomic nervous system.
AB  - This article has reviewed the laboratory evaluation of autonomic disorders.
      Autonomic testing can be divided into the assessment of three functional domains:
      sudomotor (assessed best by the thermoregulatory sweat test or QSART),
      cardiovagal (assessed by the Valsalva ratio and heart rate response to deep
      breathing or standing up), and adrenergic (assessed by the blood pressure
      response to the Valsalva maneuver or head-upright tilt). Tables 2 and 3 summarize
      the test findings in a variety of clinical disorders affecting autonomic nervous
      system function.

PMID- 12795518
TI  - Transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) is a noninvasive and painless method of
      stimulating the cerebral cortex that allows the study of cortical excitability
      and inhibition. This article describes the technique, the parameters most
      commonly studied, the clinical applications of TMS, and potential research
      applications.

PMID- 12795519
TI  - Amyotrophic lateral sclerosis and other motor neuron diseases.
AB  - The anterior horn cell diseases, with the exception of polio, are progressive
      degenerative diseases of the motor neurons. These disorders include SMA types I
      to III in children and familial and sporadic ALS and its variants (PMA, PLS, and
      PBP), Kennedy's disease, and SMA type IV in adults. The electrodiagnostic study
      is a crucial step in the diagnostic process for all of these disorders. In
      general, motor NCS may be normal or reveal low CMAP amplitudes with relatively
      normal conduction velocities. Sensory NCS, except in the case of Kennedy's
      disease, are normal. The NEE is notable for the often abundant presence of
      abnormal spontaneous activity, including fibrillation potentials and positive
      sharp waves, fasciculation potentials, and complex repetitive discharges. Motor
      unit morphology is abnormal, with polyphasic motor units and large amplitude and
      duration MUAPs when the disease is slowly progressive. Recruitment in affected
      muscles is reduced with abnormally rapidly firing motor units. To diagnose a
      widespread disorder of the motor neurons, abnormalities must be present in
      multiple muscles with different nerve root and peripheral nerve innervation in
      multiple limbs. The Lambert Criteria and the El Escorial Criteria are the two
      most widely accepted sets of electrodiagnostic criteria for ALS. The
      electrodiagnostic diagnosis must be supported by appropriate history and physical
      examination findings and the exclusion, via neuroimaging and laboratory testing,
      of other diseases that may mimic a generalized disorder of the motor neurons.

PMID- 12795520
TI  - Electrodiagnostic evaluation of hereditary motor and sensory neuropathies.
AB  - Electrodiagnosis can classify hereditary motor and sensory neuropathies (HMSN)
      into two basic types: primarily demyelinating with secondary axonal loss and
      primarily axonal. For the most part, the various forms of HMSN show uniform
      symmetric nerve conduction slowing, in contrast to acquired neuropathies, which
      may be multifocal with nonuniform conduction velocity slowing and temporal
      dispersion. Nevertheless, there are exceptions. This article reviews the
      available literature and describes the electrodiagnostic approach to HMSN,
      detailing potential sources of error that can lead to misinterpretation of data.

PMID- 12795521
TI  - Acquired peripheral neuropathy.
AB  - The element of time is a crucial factor in the electrodiagnostic presentation of
      PN. The characteristic changes seen in various neuropathies evolve over time. If
      testing is performed very early in the course of the disease, abnormalities may
      not yet be present, in part, because the range of normal values for NCS
      parameters is broad. In addition, if the process is asymmetric, the affected
      nerves may not be sampled. Very late in the course of the disease, a multifocal
      process may appear diffuse and symmetric as the areas of focal involvement
      coalesce. A primarily, demyelinating process may begin to demonstrate secondary
      axonal involvement. In very severe neuropathies, it may become difficult to evoke
      any NCS responses to characterize the neuropathy. It is essential to place the
      electrodiagnostic findings within the context of the clinical progression to
      avoid drawing erroneous conclusions. Sometimes, the true nature of the neuropathy
      is clear only after sequential testing. The etiologic diagnoses of acquired
      polyneuropathy are vast. A well-crafted electrodiagnostic evaluation can
      categorize neuropathies into more specific diagnostic groups by identifying the
      descriptive diagnosis, significantly narrowing the list of possible etiologic
      diagnoses. Electrodiagnostic testing, which always starts with a pertinent
      history and physical examination, should always be viewed as a continuation and
      quantification of the physical examination. Only by knowing the extent and
      pattern of the clinical involvement is it possible to formulate a thorough
      electrodiagnostic evaluation. This knowledge is especially important in cases in
      which the presentation is multifocal, because the neuropathy can be missed
      entirely if the affected nerves are not evaluated. When evaluating a neuropathy,
      there are three important questions to answer: (1) Is the process diffuse or
      multifocal? (2) Is it demyelinating or axonal? (3) Does it predominantly involve
      the motor or sensory nerves? By assessing the neuropathy along these three axes,
      the large number of possible etiologic diagnoses becomes much more manageable.

PMID- 12795522
TI  - Electromyographic approach to neuromuscular junction disorders repetitive nerve
      stimulation and single-fiber electromyography.
AB  - Understanding the physiology of the NMJ aids the electromyographer in
      understanding how NMJ testing was developed. Practicing the RNS protocol on
      healthy subjects helps the electromyographer gain greater comfort with the
      implementation of a test that is not performed daily. The practice parameter
      proposed by the AAEM has established guidelines for testing and for diagnosing
      NMJ disorders using RNS and single-fiber EMG.

PMID- 12795523
TI  - Myopathies.
AB  - Electrodiagnostic studies are an important adjunct to the clinical examination of
      a patient with a suspected myopathy; however, the clinical examination is crucial
      in making an accurate diagnosis, because electrodiagnostic studies have only a
      limited role in delineating with certainty the underlying myopathic disorder.
      Hereditary and acquired myopathies are reviewed in this article, with particular
      emphasis on distinguishing clinical and electrodiagnostic features. The
      hereditary myopathies that are discussed include the muscular dystrophies and the
      congenital distal mitochondrial, and metabolic myopathies. Acquired myopathies,
      including inflammatory, endocrine, and toxic myopathies, as well as those
      associated with systemic illness, are briefly reviewed.

PMID- 12795524
TI  - The changing role of pediatric electrodiagnosis.
AB  - Electrodiagnosis is one of several useful diagnostic tests in infants and
      children who have anterior horn cell disease, neuropathy, neuromuscular junction
      disorders, or myopathy. It is also used for intraoperative monitoring in
      children. For hypotonic infants and for older children with a nonspecific
      presentation of weakness, EDX may provide direction for more specific diagnostic
      testing, such as DNA testing with or without muscle biopsy. Genetic testing has
      an increasingly important role in the diagnosis of children with neuromuscular
      disorders. Future improvements in motor unit quantitation, which do not require
      active patient cooperation and require less time than current methodologies, may
      make EDX more specific and useful for diagnosing neuromuscular disease in
      children.

PMID- 12795525
TI  - Different effects of vinblastine on the polymerization of isotypically purified
      tubulins from bovine brain.
AB  - Vinblastine, a highly successful antitumor drug, targets the tubulin molecule.
      Tubulin, the subunit protein of microtubules, consists of an alpha- and a beta
      subunit, both of which consist of isotypes encoded by different genes. We have
      purified three isotypes of bovine brain tubulin, namely, alpha(beta)II,
      alpha(beta)III and alpha(beta)IV. Microtubule associated protein-2 (MAP2) and Tau
      induced assembly of these isotypes were compared in the presence and absence of
      vinblastine. MAP2-induced assembly of unfractionated tubulin and all the isotypes
      except alpha(beta)II tubulin was resistant to 1 microM vinblastine. Vinblastine
      at low concentrations (< 10 microM) progressively inhibited the assembly of all
      of the isotypes but the vinblastine concentration required for inhibition of MAP2
      induced microtubule assembly was minimal for alpha(beta)II. The tau-induced
      assembly of unfractionated tubulin and alpha(beta)III were equally sensitive to 1
      microM vinblastine whereas alpha(beta)II and alpha(beta)IV were much more
      sensitive to vinblastine. The microtubules obtained in the presence of tau from
      unfractionated tubulin, alpha(beta)II and alpha(beta)IV could be easily
      aggregated by 20 microM vinblastine whereas such as aggregation of microtubules
      obtained from alpha(beta)III and tau required approximatedly 40 microM
      vinblastine. Our results suggest that among the tubulin isotypes, alpha(beta)II
      is the most sensitive to vinblastine in the presence of MAPs while alpha(beta)III
      is the most resistant and this intrinsic resistance of alpha(beta)III dimers
      persists in the polymeric form of alpha(beta)III tubulin as well. These results
      may be relevant to the therapeutic and toxic actions of vinblastine.

PMID- 12795526
TI  - Effect of the antitumor drug vinblastine on nuclear betaII-tubulin in cultured
      rat kidney mesangial cells.
AB  - Tubulin, the main component of microtubules, is a major target for antitumor
      drugs such as vinblastine. We have recently discovered that the betaII isotype of
      tubulin is present in the nuclei of cultured rat kidney mesangial cells, smooth
      muscle-like cells present in the renal glomerular mesangium (Walss C, Kreisberg
      JI, Luduena RF: Cell Motil Cytoskeleton 42: 274-284, 1999). Here, we have
      investigated the effect of vinblastine on nuclear betaII-tubulin in these cells.
      We have found that, at concentrations of 15 nM and higher, vinblastine caused a
      reversible loss of betaII-tubulin from the nucleus. Our results raise the
      possibility that nuclear betaII-tubulin constitutes a population of tubulin that
      could be a novel target for antitumor drugs such as vinblastine.

PMID- 12795528
TI  - Discovery and preclinical antitumor efficacy evaluations of LY32262 and LY33169.
AB  - The discoveries of a new antitumor agent (LY32262) (N-[2,4
      dichlorobenzoyl]phenylsulfonamide) and a close analog (LY33169) are described.
      For this discovery, a disk-diffusion-soft-agar-colony-formation-assay was used to
      screen a portion of the Eli Lilly inventory, with the evaluation of each agent
      against normal cells, leukemic cells and several solid tumors, including a
      multidrug-resistant solid tumor (with marked selective cytotoxicity for Colon-38
      and Human-Colon-15/MDR compared to normal fibroblasts and L1210 leukemic cells
      characterizing the discovery). In mice, LY32262 and/or LY33169 had curative
      activity against Colon Adenocarcinoma-38, Human Colon-116, Human Prostate LNCaP,
      and Human Breast WSU-Br-1. In addition, many other tumors were highly sensitive:
      Panc-03 = 2.4 log kill (LK); Panc-02 = 2.9-4.1 LK; Squamous Lung LC-12 = 2.1 LK;
      Colon-26 = 2.2 LK; AML1498 = 2.7 LK; Human Sm Cell Lung DMS-273 = 6.3 LK; Human
      Squamous Lung 165 = 3.7 LK; Human Ovarian BG-1 = 3.7 LK; Human Colon CX-1 (H29) =
      1.6 LK; Human Colon-15/MDR (a p-glycoprotein positive multidrug resistant tumor)
      = 2.3 LK; Human CNS-gliosarcoma-SF295 = 3.8 LK. Several tumors were only
      marginally responsive or totally unresponsive: Mammary Adenocarcinoma-16/C = 0.6
      LK; Mammary Adenocarcinoma-17 = no kill; Colon Adenocarcinoma-11 = no kill; L1210
      leukemia = 1.3 LK; Human Prostate PC-3 = 0.5 LK; Human Adenosquamous Lung H125 =
      no kill; and Human Breast Adenocarcinoma MX-1 = 0.9 LK. There was no absolute
      tissue of origin correlation with antitumor efficacy, although colon tumors were
      most responsive and mammary tumors least responsive. The cause of the "hit and
      miss" efficacy has not been determined.

PMID- 12795527
TI  - Reversal of tumor-induced immunosuppression by TGF-beta inhibitors.
AB  - The immune system is responsible for the early detection and destruction of newly
      transformed malignant cells. Some transformed cells become immunologically
      invisible by passive avoidance of immune surveillance (i.e., when tumor cells are
      immunologically indistinguishable from normal cells). Other transformed cells
      actively secrete cytokines that effectively blind the immune system to the
      presence of abnormal antigens on the tumor cell surface. Transforming growth
      factor-beta ("TGF-beta"), which is expressed by a majority of malignant tumors,
      is the most potent immunosuppressor and therefore, the most likely cytokine to be
      responsible for the latter phenomenon. In addition to playing a key role in tumor
      induced immunosuppression, TGF-beta stimulates angiogenesis. Interestingly, tumor
      cells eventually become refractory to TGF-beta-mediated growth arrest, either due
      to loss of TGF-beta receptors or due to dysregulation in TGF-beta signaling
      pathways. Neutralization of TGF-beta or inhibition of its production is an
      effective method of cancer treatment in variety of animal models. Several agents
      targeting TGF-beta are in the early stages of development and include anti-TGF
      beta antibodies, small molecule inhibitors of TGF-beta, Smad inhibitors and
      antisense gene therapy. Since tumors may express more than one isoform of TGF
      beta, these new drugs should target all three TGF-beta isoforms produced by human
      tumors. The effects of therapies targeting TGF-beta are likely to be synergistic
      with cytotoxic chemotherapy and immunotherapy. Reversal of TGF-beta-induced
      immunosuppression is a new and promising approach to cancer therapy, with
      potential applications in other diseases such as AIDS.

PMID- 12795529
TI  - An overview on the antileukemic potential of D-homo-aza- and respective 17beta
      acetamido-steroidal alkylating esters.
AB  - In order to reduce toxicity and to increase antineoplastic activity, steroid
      molecules were utilized as biological vectors for chemotherapeutic agents.
      Several modified steroid compounds as 17beta-acetamido and D-homo-aza steroids
      that contain the NHCO group outside or inside D steroid ring, respectively, were
      used in the synthesis of steroidal esters carrying alkylating moieties. As it has
      been reported previously, several of these compounds produced important both
      antileukemic and antitumor results. In this work, we comparatively study,
      evaluate, and conclude on the acute toxicity on mice, the in vivo antileukemic
      activity against P388 and L1210 murine leukemias, as well the in vitro
      antileukemic effect on three well established human leukemia cell lines (K562,
      MOLT-4, ML-1) of eight D-homo-aza-steroidal (HASE) and the corresponding
      steroidal 17beta-amido-esters (SAE) of three alkylating molecules. The compound
      screening indicated that HASE induced lower acute toxicity and significant higher
      antileukemic effect than SAE, both in vivo and in vitro. Furthermore, the
      structure of the homo-aza-steroidal vector seems to be a determinant of the
      toxicity and antineoplastic activity of the esters. Conclusively, HASE presented
      low acute toxicity but significant high antileukemic activity. These results
      point out that HASE may be of important therapeutic efficacy in the treatment of
      leukemia in humans.

PMID- 12795530
TI  - Primary tumor, lung and kidney retention and antimetastasis effect of NAMI-A
      following different routes of administration.
AB  - Imidazolium-trans-dimethylsulfoxideimidazoletetrachlororuthenate (NAMI-A) is a
      ruthenium compound effective on solid tumor metastases. In this study, we
      evaluated the effects of different routes of administration of NAMI-A on the
      distribution to primary tumor, lungs and kidneys in BD2F1 hybrids with Lewis lung
      carcinoma or in CBA inbred mice with MCa mammary carcinoma. NAMI-A concentration
      and the percentage of cumulative dose (%Dtot) retained in these tissues is
      independent of the animal strain and of the tumor model used. Also the presence
      of the tumor does not change the distribution of NAMI-A in the lungs and in the
      kidneys. A dose-dependent antimetastatic effect is evident with intraperitoneal
      (i.p.) treatments at three different doses. Treatment of tumor bearing mice with
      NAMI-A administered i.p., per os or by aerosol showed a similar effect on lung
      metastases, although the concentration of ruthenium reached in the lungs was
      markedly different. On the basis of the data obtained, we can conclude that the
      antimetastatic effects are related to the amount of NAMI-A administered, rather
      than to the lung's concentration of the compound.

PMID- 12795531
TI  - A phase I clinical trial of spicamycin derivative KRN5500 (NSC 650426) using a
      phase I accelerated titration "2B" design.
AB  - The spicamycin derivative KRN5500 was considered as a potential anti-cancer agent
      based on in vitro and preclinical studies. A Phase I study involving 24 cancer
      patients in whom tumors were refractory to all other conventional therapies was
      conducted to determine the dose limiting toxicity, maximum tolerated dose,
      effectiveness, and pharmacokinetic parameters of this drug administered by 1-h IV
      infusion daily for five consecutive days every 3 weeks. Using an accelerated dose
      titration strategy, 8.4 mg/m2/d x 5 days was the maximum administered dose.
      Severe gastrointestinal and hepatic toxicities were observed at doses at or above
      4.3 mg/m2/d x 5. The recommended Phase II dose i s 4.3mg/m2/d x 5. The
      distribution of KRN5500 followed a two-compartment model, and clearance did not
      decrease significantly over the dose range 0.8-8.4 mg/m2/d x 5. No significant
      correlation was observed between plasma levels and toxicity. No tumor responses
      were observed among the 14 patients evaluable for response.

PMID- 12795532
TI  - A phase I and pharmacologic study of pyrazoloacridine and cisplatin in patients
      with advanced cancer.
AB  - Pyrazoloacridine (PZA, NSC366140, PD115934) is an acridine derivative currently
      undergoing clinical evaluation. In preclinical testing, PZA has shown selectivity
      for solid tumor cell lines, activity in hypoxic, noncycling, and multidrug
      resistant cell lines, and synergy with cisplatin in a variety of lung cancer cell
      lines. In early phase I clinical studies PZA has shown modest activity in
      ovarian, cervical, and colon cancer. The purpose of the present study was
      threefold: to determine the maximally tolerated doses of the combination of PZA
      (3-h infusion) and cisplatin administered with and without Filgrastim (G-CSF)
      (Amgen, Thousand Oaks, CA) every 3 weeks in untreated or minimally pretreated
      patients, to describe and quantify the clinical toxicities of combination
      chemotherapy with PZA and cisplatin, and to evaluate the effects of drug
      sequencing on the toxicity profile and pharmacologic behavior of PZA. The
      starting doses in this dose-escalation trial were PZA 400 mg/m2 as a 3-h
      intravenous infusion and cisplatin 50 mg/m2 as a 1 mg/min intravenous infusion.
      The sequence of drugs was alternated with each successive course in each patient
      treated. Twenty-one patients with refractory solid tumors received 43 courses of
      therapy through four dose levels. Neutropenia was dose-limiting and defined the
      maximum tolerated dose of PZA 400 mg/m2 and cisplatin 50 mg/m2 without G-CSF
      support. With G-CSF support, nausea and vomiting were dose-limiting. The maximum
      tolerated and recommended doses for further study of this combination are PZA 600
      mg/m2 over 3 h and cisplatin 50 mg/m2 followed by G-CSF support. Pharmacokinetic
      analysis showed that sequence does not impact on the pharmacokinetics of PZA when
      given in combination with cisplatin.

PMID- 12795533
TI  - Phase I and pharmacologic study of the human DNA methyltransferase antisense
      oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks.
AB  - PURPOSE: MG98 is a second generation phosphorothioate antisense
      oligodeoxynucleotide which is a highly specific inhibitor of translation of the
      mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity
      and pharmacologic profile of MG98 administered as a continuous 21-day intravenous
      infusion every 4 weeks. PATIENTS AND METHODS: Fourteen patients with solid
      cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240
      mg/m2/day. Steady-state concentrations of MG98 were measured as were several
      pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In
      addition, other potential surrogate markers of drug effects were explored,
      including hemoglobin F, Vimentin and GADD45. RESULTS: Dose limiting effects were
      drug-related reversible transaminase elevation and fatigue seen at doses of 240,
      200 and 160 mg/m2/day. The dose level of 80 mg/m2/day was felt to be safe and
      tolerable when delivered on this schedule. No evidence of antitumor activity was
      observed. Although pharmacokinetic analysis revealed that at the higher dose
      levels, mean Css values of MG98 were approximately 10-fold times the IC50 values
      associated with target inhibition in vitro, the extent of MG98 penetration into
      target tumors in this trial was not determined. No consistent, dose-related
      changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and
      GADD45, were observed. CONCLUSIONS: This schedule of MG98 given as a 21-day
      continuous intravenous infusion every 4 weeks was poorly tolerated in the highest
      doses; therefore, further disease-site specific evaluation of the efficacy of
      this agent will utilize a more favorable, intermittent dosing schedule.
      Pharmacodynamic evaluations undertaken in an attempt to explore and validate the
      biological mechanisms of MG98 did not show dose-related effects.

PMID- 12795534
TI  - Phase II trial of antiepidermal growth factor receptor antibody C225 in patients
      with advanced renal cell carcinoma.
AB  - Fifty-five patients with metastatic renal cell carcinoma (RCC) were treated on a
      multicenter, single-arm Phase II trial. Patients received single-agent Cetuximab
      (C225) administered by intravenous infusion at a loading dose of 400 or 500 mg/m2
      followed by weekly maintenance doses at 250 mg/m2. None of the patients treated
      with C225 achieved either a complete or partial response. The median time to
      progression was 57 days. The most frequently reported grade 3 or 4 toxicity
      treatment-related adverse events were acne (17%) and rash or dry skin (4%). The
      lack of clinical response or suggestion of prolonging time to progression
      compared to historical data with interferon-alfa supports no further study of
      single-agent C225 in patients with metastatic RCC.

PMID- 12795535
TI  - A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic
      colorectal cancer.
AB  - The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation
      Program, National Cancer Institute) has broad preclinical anti-neoplastic
      activity. Preliminary data from phase I study demonstrated antitumor activity in
      colorectal carcinoma. This phase II trial evaluates its efficacy in patients with
      minimally treated metastatic colorectal cancer. Eligibility included Karnofsky
      performance status > or = 70%, age > or = 18 years and bidimensionally measurable
      disease. Thirteen patients were treated with NSC 655649 at 500 mg/m2 by central
      venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median
      [range] 2 [1-6]) of therapy were administered. Twelve patients are eligible for
      response assessment. No major objective responses were seen using the RECIST
      criteria; however stable disease was observed in three patients with mean
      duration of 15 weeks. The median time to progression was 8 weeks. There was no
      toxic death. Four patients received only one cycle of treatment, and three had
      disease progression. Toxicities were tolerable and hematologic toxicity was the
      most common. The median (range) granulocyte and platelet nadir counts were
      2043/microl (116-16,374/microl) and 276 x 10(3)/ microl (5-769), respectively.
      Non-hematologic toxicities were moderate, including generalized weakness/fatigue,
      nausea/vomiting, diarrhea and anorexia. One patient required dose reduction;
      three patients required dose delays. NSC 655649 at this dose and schedule is
      inactive against advanced previously minimally treated metastatic colorectal
      cancer and further study of this drug as a single agent in this disease using an
      every three-week schedule is not warranted.

PMID- 12795536
TI  - Phase II study of single agent paclitaxel in adult patients with relapsed acute
      lymphocytic leukemia.
AB  - BACKGROUND: A phase II study of paclitaxel in patients with relapsed adult acute
      lymphocytic leukemia (ALL) was conducted. METHODS: Patients with relapsed ALL, no
      more than one prior salvage regimen, and no overt hepatic, renal, or cardiac
      dysfunction were eligible. Patients received paclitaxel 250 mg/m2 given as a
      continuous 24-h intravenous infusion repeated every 3-4 weeks. RESULTS: Eight
      patients received 13 courses of paclitaxel. One transient partial response was
      observed. The only severe extramedullary toxicities observed were Grade 3
      myalgias and arthralgias. CONCLUSION: The study paclitaxel regimen was
      ineffective in refractory adult ALL.

PMID- 12795538
TI  - Personal strengths of homeless adolescents living in a high-risk environment.
AB  - Health-risk behaviors and associated adverse health outcomes in homeless
      adolescents are well documented. Strengths of these youth that contribute to
      their health and well-being are seldom acknowledged. The purpose of this
      secondary analysis of qualitative data was to identify strengths that protect
      homeless youth. Two types of strengths emerged: resources and self-improvement.
      Resources served as the foundation for survival whereas self-improvement served
      as a process that enabled youth to consider a more healthy future. By recognizing
      the many strengths of homeless youth, nurses may develop community-based programs
      to help this population reenter society.

PMID- 12795537
TI  - Current approaches to novel therapeutics in pancreatic cancer.
AB  - Pancreatic cancer is one of the most refractory neoplasms to medical treatment.
      Until now there has been only modest improvement in the treatment of this
      disease. Standards of care for combined-modality treatment of resectable as well
      as locally advanced, unresectable disease have not been uniformly accepted to
      date because of an equivocal or conflicting data. The inception of gemcitabine
      introduced the new era in the management of metastatic pancreatic cancer,
      however, new therapeutic approaches still need to be defined. The article
      discusses the current knowledge of the biology of this lethal disease, its impact
      on treatment options, and explores novel therapeutic modalities that are likely
      to improve outcomes and survival for patients in the future.

PMID- 12795539
TI  - Getting critical with children: empowering approaches with a disempowered group.
AB  - The study of children and childhood has historically been accorded a marginal
      place in the health, human, and social sciences. In part, this is due to
      prevailing Western ideology that constructs children as passive, presocial,
      innocent, and vulnerable. The dominant discourse is further characterized by the
      treatment of children as a homogeneous group, devoid of race, class, or gender.
      While many investigators have described strategies for the conduct of research
      that is situated in the interpretive paradigm, there has been no comparable
      articulation of ideas regarding the conduct of critically grounded research when
      our participants are children. The purpose of this article is to put forth a
      historical and contextual analysis of childhood, including a discussion of
      evolving perspectives about childhood. The manner by which changing social,
      political, and environmental landscapes have contributed to the marginalization
      and disenfranchisement of children is examined. Finally, strategies for
      conducting nursing research that is grounded in the critical paradigmatic
      perspective, with the simultaneous aims of action, change, and empowerment, are
      proposed.

PMID- 12795540
TI  - Children's accounts of attention-deficit/hyperactivity disorder.
AB  - As a postmodern illness, attention-deficit/hyperactivity disorder (ADHD) is
      embedded in controversy, reflective of the cultural times in which we live.
      Within this debate, 2 perspectives, ADHD as myth and ADHD as behavioral disorder,
      are most frequently voiced. This article describes these 2 differing perspectives
      and reports qualitative data from 39 children and adolescents with a diagnosis of
      ADHD regarding their perceptions, meanings,and experiences of living with this
      disorder. None of the participants in this study denied that they had
      difficulties and many of the difficulties they described corresponded to DSM-IV-R
      criteria and the scientific literature. Given these discoveries, the continual
      debate about the authenticity of ADHD only further victimizes families who are in
      desperate need of services.

PMID- 12795541
TI  - Empowering preadolescents With ADHD: demons or delights.
AB  - This study tested the clinical utility of the Frame Model of Preadolescent
      Empowerment as a means of enhancing the self-perception of children diagnosed
      with attention-deficit hyperactivity disorder (ADHD). The intervention, which has
      theoretical roots in Roy's Adaptation Model, Harter's Developmental Perspective,
      and Murrell-Armstrong's Empowerment Matrix, was administered to children with
      ADHD in a pretest/posttest design. Findings indicate that this model
      significantly increased the perceptions of self-worth in preadolescents with
      ADHD.

PMID- 12795542
TI  - Guns and dolls: an exploration of violent behavior in girls.
AB  - As demonstrated by several studies, there is an increase in levels of female
      violence. This study attempts to more fully understand the increasing phenomenon
      of violence in girls by exploring motivations to engage in violent behavior. The
      hypothesis that a girl's perceived sense of competence is influenced by social
      and environmental variables that motivate her to engage in violent behavior is
      tested. Research studies of female adolescent violence have focused on the study
      of risk factors predisposing the individual to violent behavior. This study uses
      a health behavior framework (C.L. Cox, Advances in Nursing Science, October 1982,
      41-56) to explore the links between perceived sense of competence and both the
      risk and protective factors that motivate girls to act violently.

PMID- 12795543
TI  - Growing up and living with cystic fibrosis: everyday life and encounters with the
      health care and social services--a qualitative study.
AB  - The purpose of this qualitative study was to illuminate experiences of growing up
      and living with cystic fibrosis (CF). The patients' and their families'
      encounters with health care and social services were of particular interest. Four
      focus groups (adults with CF and parents of children with CF) were conducted.
      Three main themes emerged from the analysis: "From uncertainty to certainty," "A
      demanding but normal life," and "A wish for continuity, stability, and respect."
      As also documented by other studies on the chronically ill, normalization seems
      to be an important strategy, a strategy that seems not to be fully understood by
      the helpers.

PMID- 12795544
TI  - Clinical case processing by medical experts and subexperts.
AB  - Medical specialists, diagnosing cases within their domain of expertise, do not
      rely on intentional causal reasoning, in which they use explicit principles or
      rules of their domain. Rather, their reasoning has become an automatic process
      using schema-based knowledge. However, the difference between diagnoses made by
      medical specialists and diagnoses made by nonspecialists (i.e., subexperts) is
      unclear. In the present study, cardiologists (the experts), pulmonologists (the
      subexperts), and advanced medical students evaluated two clinical cases within
      the domain of cardiology. The cases were divided into four components (i.e.,
      patient's history, physical examination, laboratory data, and additional
      findings) that were sequentially presented. The task was to study, diagnose, and
      recall the segmented clinical case description. It was expected that the
      subexperts and students, as a result of their lack of specific expertise, would
      focus on different case components than the experts would. However, results
      indicated that the main difference between experts and subexperts (and to a
      lesser extent, students) was not a difference in emphasis on case components, but
      the speed and accuracy of processing these case components.

PMID- 12795545
TI  - A test of the effect of reverse speech on priming.
AB  - J. R. Vokey and J. D. Read (1985) indicated that listeners cannot consciously
      recognize backward messages but that some information can be obtained from
      reversed speech. If reverse speech has a powerful influence on language
      processing, as D. J. Oates (1991) has claimed, then one should be able to measure
      a reliable priming effect from reversed messages. Sixty undergraduate students
      listened to short messages presented either backward or forward. Immediately
      after listening to each message, they responded in a lexical decision task to a
      visually presented word that had either been present or had not been present in
      the preceding message. No priming effect was found for backward messages,
      although there was significant priming for forward messages. The results are not
      consistent with an effect of reverse speech on word processing.

PMID- 12795546
TI  - Preconceptions of taste based on color.
AB  - The authors examined preconceptions of taste based on color with a questionnaire
      administered to 45 college students. The questionnaire related 8 tastes with 10
      colors. The results suggested that only a limited number of colors are positively
      associated with preconceptions of taste. However, certain colors (e.g., red and
      green) showed consistent patterns of association with taste. Implications for
      future research examining an indirect relationship between color and taste are
      discussed.

PMID- 12795547
TI  - Testing different interpretations for the mistaken belief that rays exit the eyes
      during vision.
AB  - Research has shown that children and adults believe that emissions from the eye
      occur during the act of vision. Such beliefs are similar to ancient extramission
      theories of perception. In Study 1, the authors tested the idea that extramission
      beliefs might stem from people's thinking about what might occur during vision as
      opposed to what is necessary for seeing. Training participants to think about
      what is necessary for vision, however, had no effect on extramission responses.
      The results of Study 2 indicated that emphasizing the idea of visual input led to
      a decline in extramission responses and supported the hypothesis that
      extramission notions stem from the outer-oriented phenomenology of vision.

PMID- 12795548
TI  - Effects of induced emotional state on lexical processing in younger and older
      adults.
AB  - The authors investigated the effects of an induced emotional mood state on
      lexical decision task (LDT) performance in 50 young adults and 25 older adults.
      Participants were randomly assigned to either happy or sad mood induction
      conditions. An emotional mood state was induced by having the participants listen
      to 8 min of classical music previously rated to induce happy or sad moods.
      Results replicated previous studies with young adults (i.e., sad-induced
      individuals responded faster to sad words and happy-induced individuals responded
      faster to happy words) and extended this pattern to older adults. Results are
      discussed with regard to information processing, aging, and emotion.

PMID- 12795549
TI  - Sportsmanship in young athletes: the role of competitiveness, motivational
      orientation, and perceived purposes of sport.
AB  - The purpose of the study was to evaluate measures of competitiveness,
      motivational orientation, and perceived purposes of participation as predictors
      of sportsmanship in a sample of 319 young participants in sports. Hierarchical
      regression analyses indicated that intrinsic reasons for sports participation,
      such as enhanced self-esteem and task mastery, predicted higher levels on
      multiple dimensions of sportsmanship, above and beyond the influence of
      competitiveness, motivational orientation, and various demographic variables. In
      contrast, extrinsic purposes for participation in sports, such as to obtain
      social status and a high-status career, contributed to lower levels on 3 of the 4
      sportsmanship dimensions. These results are discussed with regard to developing a
      competitive sport setting that promotes ethical standards of interpersonal
      behavior for young participants in sports.

PMID- 12795550
TI  - How do romantic relationship satisfaction, gender stereotypes, and gender relate
      to future time orientation in romantic relationships?
AB  - The present study is an investigation into how romantic relationship satisfaction
      and attitudes toward gender stereotypes about romantic relationship and gender
      are related to future time orientation in romantic relationships (FTORR). Four
      hundred and thirteen (208 men and 205 women) university students taking elective
      psychology courses at Middle East Technical University were given a scale
      including items about FTORR, romantic relationship satisfaction, and attitudes
      toward gender stereotypes about romantic relationships. All the participants were
      then involved in a heterosexual romantic relationship. Multiple regression
      results showed that for the women, attitudes toward men's assertiveness and men's
      dominance in relationships were more important predictors of FTORR than
      relationship satisfaction. For the men, attitudes toward men's assertiveness and
      romantic relationship satisfaction were important predictors of FTORR, but
      attitude toward men's dominance was not a predictor of FTORR. Women were more
      future oriented in their ongoing romantic relationships than were men. Finally,
      participants who were highly satisfied with their relationships scored higher on
      FTORR than those who were less satisfied.

PMID- 12795551
TI  - International arena of ultrasound education.

PMID- 12795552
TI  - Sacroiliac joint injections performed with sonographic guidance.
AB  - OBJECTIVE: To investigate the feasibility and effectiveness of sonographic
      guidance for therapeutic intra-articular sacroiliac joint injections in patients
      with sacroiliitis. METHODS: Thirty-four consecutive patients with sacroiliitis
      were enrolled in this study. The synovial portions of 60 sacroiliac joints
      received injections under sonographic guidance. For treatment, a mixture of a
      corticosteroid and a local anesthetic was injected intra-articularly.
      Fluoroscopic spot images were obtained to assess the accuracy of the
      sonographically guided technique. RESULTS: Of the 60 sonographically guided
      injections, 46 (76.7%) were successful (i.e., intra-articular), and 14 (23.3%)
      were missed. The successful intra-articular injection rate was 60% in the first
      30 injections, and it gradually improved, reaching 93.5% in the last 30
      injections. The mean procedure time was 9 minutes. CONCLUSIONS: Our initial
      experience suggests that sonographically guided therapeutic injections to
      sacroiliac joints could be valuable alternatives to other guidance modalities in
      patients with sacroiliitis. In the hands of experienced radiologists, this
      technique is safe, rapid, and reproducible.

PMID- 12795553
TI  - Filling of the bladder for pelvic sonograms.

PMID- 12795554
TI  - Transabdominal sonography before uterine exploration as a predictor of retained
      placental fragments.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of sonography in postpartum
      patients thought to have retained placental fragments. METHODS: The study group
      consisted of 39 postpartum women in whom inspection of the placenta brought up
      suspicion of retained placental fragments. All these women underwent manual
      exploration of the uterine cavity. Before the procedure, all patients had two
      dimensional sonographic imaging, after which they were divided into 2 groups. The
      first group comprised women who were judged to have had an empty uterus or
      nothing but intrauterine fluid collection. The second group consisted of those in
      whom sonography showed echoes of what might appear as residual trophoblastic
      tissue, that is, echogenic, hypoechoic, or mixed echo intracavitary patterns. The
      sonographic patterns were then correlated with the presence or absence of
      retained placental fragments as found on uterine manual exploration and
      pathologic examination. RESULTS: In 18 patients, no suspected contents were
      observed on sonography. In 17 of these patients, the uterus was empty on manual
      uterine exploration. One of these patients had residual trophoblastic tissue,
      which was of minimal quantity and clinically unimportant. In 21 patients,
      sonography suggested retained placental tissue. In 15 of these patients,
      pathologic examination confirmed residual trophoblastic tissue, and in the
      remaining 6, the uterus contained blood clots, decidua, or both. CONCLUSIONS:
      Sonography is an effective tool for evaluating postpartum patients thought to
      have retained placental fragments. Normal sonographic findings might obviate the
      need for manual exploration of the uterine cavity. A questionable sonographic
      result is not an effective tool for distinguishing between placental fragments
      and blood clots.

PMID- 12795555
TI  - Three-dimensional ultrasonographic appearance of the fetal akinesia deformation
      sequence.
AB  - OBJECTIVE: To present the appearance of the fetal akinesia deformation sequence
      by three-dimensional ultrasonography after four-dimensional ultrasonographic
      scanning. METHODS: Three-dimensional surface-rendering images were used to show
      the fixed postural abnormalities of the fetal extremities and body. Four
      dimensional ultrasonography was used to show that the postural abnormalities were
      fixed and to confirm the absence of fetal movements. These images were compared
      with the postmortem examination findings. RESULTS: Three-dimensional
      ultrasonographic images of 3 cases of fetal akinesia deformation sequence are
      presented. Surface-rendering imaging and imaging in the skeletal mode were
      performed to show the postural abnormalities and the arthrogryposis. CONCLUSIONS:
      Facilitated by polyhydramnios, three- and four-dimensional ultrasonography
      provided clear images of the fixed postural abnormalities, which were confirmed
      by postmortem examination. Although prenatal diagnosis can be easily made by
      conventional ultrasonography, three-dimensional ultrasonography might be used as
      a confirmatory approach. In addition, the quality of recent three-dimensional
      imaging might help prenatal counseling by providing images more readily
      understandable to the parents than those obtained by two-dimensional
      ultrasonography.

PMID- 12795556
TI  - Color Doppler sonohysterography of endometrial polyps and submucosal fibroids.
AB  - OBJECTIVE: To describe the typical sonographic findings and clinical applications
      of color Doppler sono-hysterography and to correlate the vascularity of lesions
      seen on color Doppler sonohysterography to microvessel density and the presence
      of vessels greater than 0.5 mm. METHODS: Color Doppler sonohysterography was
      performed on 25 women with abnormal uterine bleeding. The vascularity (number of
      vessels > 0.5 mm) and their configuration seen on color Doppler sonohysterography
      were compared with those obtained on the excised specimen. Microvessel density
      and histologic features were correlated to the visualization of vessels greater
      than 0.5 mm and their arrangement on color Doppler sonography. RESULTS: The color
      Doppler sonographic findings in 18 polyps, 3 submucosal fibroids, and 1 clot
      showed distinct vascularity patterns. Polyps typically contained a single feeding
      vessel, whereas fibroids had several vessels, which arose from the inner
      myometrium. Lesions with higher microvessel density tended to have more vessels
      greater than 0.5 mm as depicted on color Doppler sonography. CONCLUSIONS: Color
      Doppler sonohysterography may be useful in distinguishing polyps from submucosal
      fibroids based on the vascularity of the lesions. The number of vessels seen on
      color Doppler sonography approximates microvessel density within the lesions.

PMID- 12795557
TI  - Prostate boundary detection from ultrasonographic images.
AB  - OBJECTIVE: Prostate diseases are very common in adult and elderly men, and
      prostate boundary detection from ultrasonographic images plays a key role in
      prostate disease diagnosis and treatment. However, because of the poor quality of
      ultrasonographic images, prostate boundary detection still remains a challenging
      task. Currently, this task is performed manually, which is arduous and heavily
      user dependent. To improve the efficiency by automating the boundary detection
      process, numerous methods have been proposed. We present a review of these
      methods, aiming to find a good solution that could efficiently detect the
      prostate boundary on ultrasonographic images. METHODS: A full description of
      various methods is beyond the scope of this article; instead, we focus on
      providing an introduction to the different methods with a discussion of their
      advantages and disadvantages. Moreover, verification methods for estimating the
      accuracies of the algorithms reported in the literature are discussed as well.
      RESULTS: From the investigation, we summarize several key issues that might be
      confronted and project possible future research. CONCLUSIONS: Those model-based
      methods that minimize user involvement but allow for interactive guidance of
      experts will likely be most immediately successful.

PMID- 12795558
TI  - Evaluation of extremity trauma with sonography.
AB  - OBJECTIVE: To report on the use of bedside sonography in the diagnosis and
      treatment of penetrating extremity trauma. METHODS: Sonography was performed in
      the emergency department of a level 1 trauma center with both curved and linear
      array transducers. RESULTS: In both cases, foreign bodies and fractures resulting
      from gunshot wounds to the extremities were found. In addition, intra-abdominal
      and thoracic injuries were evaluated for using sonography. CONCLUSIONS: The
      increasing mobility and portability of sonography has led to its increasing use
      at the patient' bedside to diagnose a variety of conditions. It provides
      potential immediate diagnosis and has the flexibility for evaluating a multitude
      of injuries normally requiring several different imaging technologies. In
      circumstances in which conventional radiography is unavailable, such as at trauma
      scenes, mass casualty situations, or at the bedside with unstable patients,
      sonography can provide unique and essential information about these patients.

PMID- 12795559
TI  - Ultrasonography for depiction of brachial plexus injury.
AB  - Recent development of ultrasonographic equipment has allowed improved spatial
      resolution for visualizing normal and pathologic conditions of peripheral nerves.
      Regarding the brachial plexus, only ultrasonographic studies that have described
      the normal appearance have been reported. To the best of our knowledge, no case
      report regarding the ultrasonographic description of a brachial plexus lesion has
      been published. We report the ultrasonographic findings of a brachial plexus
      injury after extirpation of a suspected enlarged supraclavicular lymph node.

PMID- 12795560
TI  - Sonographic diagnosis of talar lateral process fracture.
AB  - The frequency of fractures of the lateral process of the talus (LPT) has markedly
      increased because of the expansion of snowboard activity. These lesions are
      difficult to diagnose, because they have aspecific signs, and standard
      radiographs do not show the fractures in 50% of cases. Sonography is used more
      and more in the assessment of ankle trauma, but it is rarely performed for
      detection of bone fractures. We report a case of a patient in which sonography
      directly showed an LPT fracture.

PMID- 12795561
TI  - Duplication of the superficial femoral artery diagnosed primarily on the basis of
      color Doppler ultrasonography.
AB  - Variations of the lower extremity venous system are common, and radiologists may
      frequently be confronted with such variations during daily clinical practice.
      However, variations in the arterial system of the lower extremity are extremely
      rare. The profunda femoris artery and arteries of the cruris are mainly subject
      to variation. This report describes an extremely rare arterial variation,
      duplication of the superficial femoral artery (SFA), in terms of the radiologic
      findings, clinical importance, and embryologic basis.

PMID- 12795562
TI  - Lethal progression of a fetal intracranial arteriovenous malformation.
AB  - Fetal intracranial vascular tumors present unique clinical challenges. Accurate
      diagnosis of the lesion, as well as an understanding of the local and systemic
      impacts, will guide the antenatal surveillance and the treatment plan and will
      determine the prognosis. Management will be altered by and dependent on
      intrauterine progression, gestational age, and fetal condition at birth. In
      addition, large vascular tumors can lead to the development of the Kasabach
      Merritt sequence in the fetus and to either fetal or maternal hemodynamic
      impairment. Vascular tumors are either malformations or neoplasms. Color and
      pulsed wave Doppler sonography are useful for the identification of vascular
      lesions and help narrow the differential diagnosis. Once a vascular malformation
      is identified, a comprehensive anatomic survey is mandatory to determine whether
      there are coexistent malformations that impact either the diagnosis or prognosis.
      These lesions can have local mass effects, systemic hemodynamic effects, or both.
      Therefore, longitudinal assessment of the fetus is focused on the detection of
      lesion progression and on any fetal or maternal status changes. We report the
      prenatal diagnosis of an intracranial arteriovenous malformation (AVM) with a
      dramatic progression affecting both mother and fetus.

PMID- 12795563
TI  - Sonographic detection of in utero isolated cerebellar hemorrhage.
AB  - Cerebellar hemorrhage is a relatively rare phenomenon in neonates, and most cases
      are associated with intraventricular hemorrhage (IVH). Prenatally diagnosed
      intracranial hemorrhage is rare, and diagnoses of cerebellar hemorrhage are even
      rarer. In our literature search, we discovered 3 cases of prenatal diagnosis of
      cerebellar hemorrhage, all accompanied by IVH. None of the neonates survived. We
      report a case initially observed in utero by sonography of cerebellar hemorrhage
      without evidence of IVH, causing ventriculomegaly in a 32-week twin fetus who was
      subsequently successfully treated.

PMID- 12795564
TI  - Antenatal detection of idiopathic arterial calcification with hydrops fetalis.
AB  - Idiopathic arterial calcification of infancy, or occlusive infantile arterial
      calcification, is a rare cause of arterial calcification. This condition is
      inherited as an autosomal recessive pattern, which is almost always fatal. In
      most of the 100 cases described in the literature, the diagnosis was made at
      autopsy; a few cases have been reported in which an antemortem diagnosis was made
      on the basis of radiographic or sonographic demonstration of arterial
      calcification. The clinical characteristics are extremely variable, and
      respiratory distress with cardiac failure is the most common finding.
      Hypertension that is refractory to treatment is present in most cases. Most
      infants die before the age of 6 months, and very few have survived for more than
      1 year. Mortality in this condition is caused by myocardial ischemia due to
      coronary artery involvement or refractory cardiac failure. The purpose of this
      report is to describe the prenatal diagnosis of idiopathic arterial
      calcification. Fewer than 10 cases of antenatal detection of this condition have
      been reported in the literature. This case is 1 of 2 cases with the earliest
      diagnosis of this condition so far (Table 1).

PMID- 12795565
TI  - Gilbert Baum, MD, 1922-2002, a pioneer in ultrasound.

PMID- 12795566
TI  - Kenneth J. Taylor, MD, PhD, FACP, 1939-2003, pioneer of diagnostic ultrasound
      imaging.

PMID- 12795567
TI  - Posttraumatic stress disorder following assault: the role of cognitive
      processing, trauma memory, and appraisals.
AB  - Two studies of assault victims examined the roles of (a) disorganized trauma
      memories in the development of posttraumatic stress disorder (PTSD), (b)
      peritraumatic cognitive processing in the development of problematic memories and
      PTSD, and (c) ongoing dissociation and negative appraisals of memories in
      maintaining symptomatology. In the cross-sectional study (n = 81), comparisons of
      current, past, and no-PTSD groups suggested that peritraumatic cognitive
      processing is related to the development of disorganized memories and PTSD.
      Ongoing dissociation and negative appraisals served to maintain PTSD symptoms.
      The prospective study (n = 73) replicated these findings longitudinally.
      Cognitive and memory assessments completed within 12-weeks postassault predicted
      6-month symptoms. Assault severity measures explained 22% of symptom variance;
      measures of cognitive processing, memory disorganization, and appraisals
      increased prediction accuracy to 71%.

PMID- 12795569
TI  - Prediction of violence and self-harm in mentally disordered offenders: a
      prospective study of the efficacy of HCR-20, PCL-R, and psychiatric
      symptomatology.
AB  - The efficacy of the Historical, Clinical, and Risk Management Scales (HCR-20; C.
      D. Webster, D. Eaves, K. S. Douglas, & A. Wintrup, 1995), Psychopathy Checklist
      Revised (PCL-R; R. D. Hare, 1991), Beck Hopelessness Scale (BHS; A. T. Beck, A.
      Weissman, D. Lester, & L. Trexler, 1974), and Brief Psychiatric Rating Scale
      (BPRS) to predict violence and self-harm in 34 institutionalized mentally
      disordered offenders was assessed. Both the HCR-20 and BPRS were strong
      predictors of violence whereas the PCL-R had moderate predictive ability. BHS was
      the only variable predictive of self-harm. Although risk assessment measures were
      successful at predicting in-patient violence, a clinical measure of mental state
      was at least as effective in these mentally disordered offenders.

PMID- 12795568
TI  - Behavioral family counseling and naltrexone for male opioid-dependent patients.
AB  - Men (N = 124) entering treatment for opioid dependence who were living with a
      family member were randomly assigned to one of two 24-week treatments: (a)
      behavioral family counseling (BFC) plus individual treatment (patients had both
      individual and family sessions and took naltrexone daily in presence of family
      member) or (b) individual-based treatment only (IBT; patients were given
      naltrexone and were asked in counseling sessions about their compliance, but
      there was no family involvement). BFC patients, compared with their IBT
      counterparts, ingested more doses of naltrexone, attended more scheduled
      treatment sessions, had more days abstinent from opioids and other drugs during
      treatment and during the year after treatment, and had fewer drug-related, legal,
      and family problems at 1-year follow-up.

PMID- 12795570
TI  - Prediction of treatment outcome from relationship variables in child and
      adolescent therapy: a meta-analytic review.
AB  - Results from 23 studies examining associations between therapeutic relationship
      variables and treatment outcomes in child and adolescent therapy were reviewed
      with meta-analytic procedures. Results indicated that the overall strength of the
      relationship-outcome associations was modest and quite similar to results
      obtained with adults. This modest association was moderated by 1 substantive
      factor, type of patient problem, and 5 methodological factors, timing and source
      of relationship measurement, type and source of outcome, and shared versus cross
      source measurement of relationship and outcome variables. Type, mode, structure,
      and context of treatment did not moderate associations between relationship
      variables and outcomes. Findings indicated that the association between the
      therapeutic relationship and treatment outcome was consistent across
      developmental levels and across diverse types and contexts of child and
      adolescent therapy. Recommendations for future process research on the
      therapeutic relationship in child psychotherapy are offered.

PMID- 12795571
TI  - Relations of positive and negative affectivity to anxiety and depression in
      children: evidence from a latent variable longitudinal study.
AB  - The tripartite model of anxiety and depression has been studied with adults;
      however, support is still emerging with children concerning measurement and
      relations between positive (PA) and negative (NA) affect and psychopathology. In
      this longitudinal study of 270 4th- to 11th-grade children (mean age = 12.9
      years, SD = 2.23). confirmatory factor analysis supported a 2-factor orthogonal
      model of children's self-reported affect and revealed that the concurrent
      relations of NA and PA to anxiety and depression symptoms were consistent with
      the tripartite model. Structural equation modeling demonstrated moderate cross
      time stability of trait PA and NA, consistent with a temperament view of these
      factors, as well as partial support for the role of NA and PA in the development
      of anxiety and depression symptoms in children.

PMID- 12795572
TI  - Family-focused treatment versus individual treatment for bipolar disorder:
      results of a randomized clinical trial.
AB  - Recently hospitalized bipolar, manic patients (N = 53) were randomly assigned to
      a 9-month, manual-based, family-focused psychoeducational therapy (n = 28) or to
      an individually focused patient treatment (n = 25). All patients received
      concurrent treatment with mood-stabilizing medications. Structured follow-up
      assessments were conducted at 3-month intervals for a 1-year period ofactive
      treatment and a 1-year period of posttreatment follow-up. Compared with patients
      in individual therapy, those in family-focused treatment were less likely to be
      rehospitalized during the 2-year study period. Patients in family treatment also
      experienced fewer mood disorder relapses over the 2 years, although they did not
      differ from patients in individual treatment in their likelihood of a first
      relapse. Results suggest that family psychoeducational treatment is a useful
      adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization
      frequently associated with bipolar disorder.

PMID- 12795573
TI  - Lowering risk for early alcohol use by challenging alcohol expectancies in
      elementary school children.
AB  - Altering alcohol expectancies has reduced alcohol use among young adults and may
      lead to successful prevention of early alcohol use. The authors randomly assigned
      216 4th-grade children to an expectancy challenge or control condition and used
      individual-differences scaling to map expectancies into memory network format,
      with preference mapping to model likely paths of association. After expectancy
      intervention, children exhibited a greater likelihood to associate alcohol use
      with negative and sedating consequences and a decreased likelihood to associate
      alcohol with positive and arousing consequences. Children and adults who
      emphasize negative and sedating effects have been found to be less likely touse
      alcohol. Therefore, expectancy challenge interventions that have been successful
      at modifying expectancies and subsequently decreasing alcohol consumption of
      adults may be useful in reducing the likelihood of early alcohol use among
      children.

PMID- 12795574
TI  - Treatment of parental stress to enhance therapeutic change among children
      referred for aggressive and antisocial behavior.
AB  - This study evaluated a parent problem-solving (PPS) intervention designed to
      augment the effects of evidence-based therapy for children referred to treatment
      for aggressive and antisocial behavior. All children (N = 127, ages 6-14 years)
      and their families received problem-solving skills training (PSST), and parents
      received parent management training (PMT). Families were randomly assigned to
      receive or not to receive an additional component (PPS) that addressed parental
      stress over the course of treatment. Children improved with treatment; the PPS
      intervention enhanced therapeutic change for children and parents and reduced the
      barriers that parents experienced during treatment. The implications of the
      findings for improving evidence-based treatment as well as the limitations of
      adding components to treatment are detailed.

PMID- 12795575
TI  - When syndromal similarity obscures functional dissimilarity: distinctive evoked
      environments of externalizing and mixed syndrome boys.
AB  - This research examined how syndromal approaches to assessment can obscure
      differences between children in the quality of their social interactions. Mixed
      boys (high for externalizing and internalizing problems) showed heterogeneity in
      the responses they evoked from others: For one subgroup, aggression and
      withdrawal evoked aversive responses from others, and even prosocial behavior
      evoked hostile peer responses; for the other, aggression and withdrawal evoked
      positive peer responses. Externalizing boys also showed heterogeneity in the
      patterning of their evoked responses. Within-group heterogeneity was not
      explained by boys' syndrome scores but was linked to their reactions to specific
      antecedent events. The results illustrate how a contextualized analysis of
      behavior can reveal distinctive social interactional patterns that underlie
      similar overall rates of problem behaviors.

PMID- 12795576
TI  - Gender, victimization, and outcomes: reconceptualizing risk.
AB  - Large-scale studies of gender differences in psychopathological reactions to
      victimization have focused on posttraumatic stress disorder, overlooking other
      trauma-related disorders. The present study expands this literature with a
      contextualized examination of interpersonal aggression exposure and sequelae.
      Using k-means cluster analysis on a sample of 16,000, the authors identified 8
      distinct profiles of exposure to sexual violence, physical assault, stalking, and
      emotional abuse. Analyses of covariance then suggested links among victimization
      profile, gender, and mental and physical health. Results revealed no meaningful
      interactive effects of gender and interpersonal aggression on outcomes, once
      lifetime exposure to aggressive events was adequately taken into account. These
      findings argue against theories of female victims' greater vulnerability to
      pathological outcomes, instead linking risk to exposure history.

PMID- 12795577
TI  - Which treatment for whom for ADHD? Moderators of treatment response in the MTA.
AB  - Using receiver operating characteristics, the authors examined outcome predictors
      (variables associated with outcome regardless of treatment) and moderators
      (variables identifying subgroups with differential treatment effectiveness) in
      the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity
      Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher
      reported ADHD and oppositional defiant symptoms, with levels near or within the
      normal range indicating excellent response. Among 9 baseline child and family
      characteristics, none predicted but 3 moderated treatment response. In medication
      management and combined treatments, parental depressive symptoms and severity of
      child ADHD were associated with decreased rates of excellent response; when these
      2 characteristics were present, below-average child IQ was an additional
      moderator. No predictors or moderators emerged for behavioral and community
      comparison treatments. The authors discuss conceptual and clinical implications
      of research on treatment moderators.

PMID- 12795578
TI  - Individuation, peers, and adolescent alcohol use: a latent growth analysis.
AB  - The study used latent growth modeling to investigate longitudinal relationships
      between individuation, peer alcohol use, and adolescent alcohol use among African
      American, Mexican American, and non-Hispanic White adolescents (N = 6,048) from
      7th, 8th, and 9th grades over a 3-year period. Initial levels of peer alcohol use
      were significantly related to changes in adolescents' alcohol use, whereas
      initial adolescent alcohol use also significantly related to changes in peers'
      alcohol use, suggesting a bidirectional relationship. Higher levels of
      intergenerational individuation were related to smaller increases in adolescent
      alcohol use and higher levels of separation were related to larger increases in
      youth drinking. The findings were similar across ethnic groups. Implications for
      development of prevention and intervention programs are discussed.

PMID- 12795579
TI  - Extended telephone counseling for smoking cessation: does content matter?
AB  - Telephone counseling is a popular modality for smoking cessation treatment;
      however, little attention has been paid to evaluating the efficacy of different
      contents of calls. This study compared 2 types of proactive telephone calls
      following a group program. Participants were randomized to receive either: (a)
      basic content, consisting primarily of support; or (b) enhanced content, tailored
      to the stage of cessation (still smoking, abstinent, or relapsed) and targeting
      factors hypothesized to be related to success (motivation, self-efficacy, and
      negative mood). There was a significant interaction between treatment condition
      and gender. For men, the enhanced condition produced better abstinence rates
      through 15 months and lower relapse rates. For women, the basic condition was
      better. History of depression did not interact with condition.

PMID- 12795580
TI  - A prospective investigation of the impact of childhood sexual abuse on the
      development of sexuality.
AB  - The sexual attitudes and activities of 77 sexually abused and 89 comparison women
      (mean age = 20.41, SD = 3.38) were assessed 10 years after disclosure in a
      longitudinal, prospective study of the long-term effects of childhood sexual
      abuse. Abused participants were more preoccupied with sex, younger at first
      voluntary intercourse, more likely to have been teen mothers, and endorsed lower
      birth controlefficacy than comparison participants. When psychological
      functioning earlier in development was examined, sexual preoccupation was
      predicted by anxiety, sexual aversion was predicted by childhood sexual behavior
      problems, and sexual ambivalence (simultaneous sexual preoccupation and sexual
      aversion) was predicted by pathological dissociation. Findings also indicate that
      biological father abuse may be associated with greater sexual aversion and sexual
      ambivalence.

PMID- 12795581
TI  - The family bereavement program: efficacy evaluation of a theory-based prevention
      program for parentally bereaved children and adolescents.
AB  - This article presents an experimental evaluation of the Family Bereavement
      Program (FBP), a 2-component group intervention for parentally bereaved children
      ages 8-16. The program involved separate groups for caregivers, adolescents, and
      children, which were designed to change potentially modifiable risk and
      protective factors for bereaved children. The evaluation involved random
      assignment of 156 families (244 children and adolescents) to the FBP or a self
      study condition. Families participated in assessments at pretest, posttest, and
      11-month follow-up. Results indicated that the FBP led to improved parenting,
      coping, and caregiver mental health and to reductions in stressful events at
      posttest. At follow-up, the FBP led to reduced internalizing and externalizing
      problems, but only for girls and those who had higher problem scores at baseline.

PMID- 12795582
TI  - Multilevel selected primary prevention of child maltreatment.
AB  - Few treatment studies and even fewer primary prevention studies have demonstrated
      successful reduction of child maltreatment. Successful preventive interventions
      have often been lengthy and expensive; shorter programs have been didactic and
      ineffective. The present investigation relied on a 7-level model of successful
      parenting to mount a time-limited, "selected" prevention effort with high-risk
      mothers. This program included modeling, role-playing, Socratic dialogue, home
      practice, and home visits. The study demonstrated effective intervention at every
      level of the model, including improvements in (a) parenting skills, (b)
      developmentally appropriate interventions, (c) developmentally appropriate
      beliefs, (d) negative affect, (e) acceptance of a responsible parent role, (f)
      acceptance of a nurturing parent role, and (g) self-efficacy. Directions for
      future research are considered.

PMID- 12795583
TI  - The association between emotional upset and cardiac arrhythmia during daily life.
AB  - Ventricular arrhythmia exhibits considerable within-subject variability that
      cannot be attributed to clinical status alone. This investigation examined the
      extent to which cardiac arrhythmia was associated with psychological and physical
      factors assessed during the hour preceding arrhythmic or nonarrhythmic activity.
      Approximately twice hourly, 46 patients randomly completed a diary assessing mood
      and physical symptoms during 24-hr electrocardiographic monitoring. Greater
      negative emotion was associated with increased arrhythmia. Additionally, greater
      negative emotion was significantly associated with increased arrhythmia among
      participants in a low left ventricular ejection fraction group (LVEF). However,
      this relationship between negative emotion and arrhythmia was not observed among
      higher LVEF participants. These findings contribute to a larger body of evidence
      suggesting that negative moods may exacerbate cardiac conditions.

PMID- 12795584
TI  - Day treatment with contingency management for cocaine abuse in homeless persons:
      12-month follow-up.
AB  - Abstinence, employment, and homelessness treatment outcomes at 12-month follow-up
      are presented from a study comparing behavioral day treatment plus abstinence
      contingent housing and work therapy with behavioral day treatment only among
      homeless persons who abuse crack cocaine. Within-group improvements were
      revealed, but group differences for drug abstinence found in J. B. Milby et al.
      (2000) failed to persist at 12 months. Drug use measurement and treatment
      termination explanations are discussed. Within- but not between-group differences
      were found for employment and homelessness outcomes at long-term follow-up.
      Research extending abstinence contingencies and continuous drug use monitoring is
      recommended. Questions about effectiveness of contingency management alone, role
      of coexisting psychiatric disorders on treatment outcome, and individualized
      treatment dosing are offered.

PMID- 12795585
TI  - The prevention of depressive symptoms in rural school children: a randomized
      controlled trial.
AB  - A controlled trial was conducted to evaluate a prevention program aimed at
      reducing depressive and anxious symptoms in rural school children. Seventh-grade
      children with elevated depression were selected. Nine primary schools (n = 90)
      were randomly assigned to receive the program, and 9 control schools (n = 99)
      received their usual health education classes. Children completed questionnaires
      on depression, anxiety, explanatory style, and social skills. Parents completed
      the Child Behavior Checklist (T. M. Achenbach, 1991). No intervention effects
      were found for depression. Intervention group children reported less anxiety than
      the control group after the program and at 6-month follow-up and more optimistic
      explanations at postintervention. Intervention group parents reported fewer child
      internalizing and externalizing symptoms at postintervention only.

PMID- 12795586
TI  - Role of perfectionism and personality disorder features in response to brief
      treatment for depression.
AB  - Using data from the Treatment of Depression Collaborative Research Program
      (TDCRP), the authors compared the role of patients' perfectionism and features of
      personality disorder (PD) in the outcome of brief treatment for depression. Data
      were extracted as to patients' intake levels of symptoms; perfectionism; and PD
      features, measured as continuous variables, as well as their symptoms at
      termination; their contribution to the therapeutic alliance; and their
      satisfaction with social relations. Poorer therapeutic outcome was demonstrated
      for patients with elevated levels of perfectionism and odd-eccentric and
      depressive PD features. Patients' contribution to therapeutic alliance and
      satisfaction with social relations were predicted by perfectionism but not by PD
      features. Results highlight the central role played by patients' personality in
      the course of brief treatment for depression.

PMID- 12795587
TI  - A microsomal endopeptidase from liver that preferentially degrades stearoyl-CoA
      desaturase.
AB  - A protease was purified some 700-fold from rat liver microsomes by a combination
      of differential detergent solubilization, hydroxyapatite column chromatography,
      and gel filtration. The protease exhibits substrate selectivity for stearoyl-CoA
      desaturase (SCD). The purified protease rapidly degraded SCD while other
      microsomal proteins including cytochrome b(5) and 11beta-hydroxysteroid
      dehydrogenase were degraded slowly or not at all. The isolated form of the
      protease has an apparent molecular mass of approximately 90 kDa. Upon incubation,
      the 90 kDa form of the protease undergoes rapid conversion to a series of smaller
      proteins. This conversion is associated with a marked increase in proteolytic
      activity. Diisopropyl phosphofluoridate (DFP) at high concentration partially
      inhibited the protease activity. The [(3)H]DFP-labeled protease was detected as
      three protein bands of approximately 66 kDa under nonreducing conditions and a
      single 25 kDa band under reducing conditions. The purified protease was inhibited
      by dithiothreitol, suggesting the presence of an essential disulfide bond. These
      results further define the mechanism by which SCD is rapidly and selectively
      degraded in isolated liver microsomes.

PMID- 12795589
TI  - Characterizing the unstructured intermediates in oxidative folding.
AB  - A recently developed method is used here to characterize some of the folding
      intermediates, and the oxidative folding processes, of RNase A. This method is
      based on the ability of trans-[Pt(en)(2)Cl(2)](2+) to oxidize cysteine residues
      to form disulfide bonds faster than the disulfide bonds can be rearranged by
      reshuffling or reduction. Variations of this method have enabled us to address
      three issues. (i) How the nature of the residual structure and/or conformational
      order that is present, or develops, during the initial stages of folding can be
      elucidated. It is shown here that there is a 10-fold increase in the propensity
      of the unfolded reduced forms of RNase A to form the native set of disulfides
      directly, compared to the propensity under strongly denaturing conditions (4-6 M
      GdnHCl). Thus, the unfolded reduced forms of RNase A are not statistical coils
      with a more condensed form than in the GdnHCl-denatured state; rather, it is
      suggested that reduced RNase A has a little bias toward a native topology. (ii)
      The structural characterization of oxidative folding intermediates in terms of
      disulfide pairing is demonstrated; specifically, a lower-limit estimate is made
      of the percentage of native disulfide-containing molecules in the two-disulfide
      ensemble of RNase A. (iii) The critical role of structured intermediate species
      in determining the oxidative folding pathways of proteins was shown previously.
      Here, we demonstrate that the presence of a structured intermediate in the
      oxidative folding of proteins can be revealed by this method.

PMID- 12795588
TI  - Primary sequence characterization of catestatin intermediates and peptides
      defines proteolytic cleavage sites utilized for converting chromogranin a into
      active catestatin secreted from neuroendocrine chromaffin cells.
AB  - Catestatin is an active 21-residue peptide derived from the chromogranin A (CgA)
      precursor, and catestatin is secreted from neuroendocrine chromaffin cells as an
      autocrine regulator of nicotine-stimulated catecholamine release. The goal of
      this study was to characterize the primary sequences of high molecular mass
      catestatin intermediates and peptides to define the proteolytic cleavage sites
      within CgA that are utilized in the biosynthesis of catestatin. Catestatin
      containing polypeptides, demonstrated by anti-catestatin western blots, of 54-56,
      50, 32, and 17 kDa contained NH(2)-terminal peptide sequences that indicated
      proteolytic cleavages of the CgA precursor at KK downward arrow, KR downward
      arrow, R downward arrow, and KR downward arrow basic residue sites, respectively.
      The COOH termini of these catestatin intermediates were defined by the presence
      of the COOH-terminal tryptic peptide of the CgA precursor, corresponding to
      residues 421-430, which was identified by MALDI-TOF mass spectrometry. Results
      also demonstrated the presence of 54-56 and 50 kDa catestatin intermediates that
      contain the NH(2) terminus of CgA. Secretion of catestatin intermediates from
      chromaffin cells was accompanied by the cosecretion of catestatin (CgA(344)(
      )(364)) and variant peptide forms (CgA(343)(-)(368) and CgA(332)(-)(361)). These
      determined cleavage sites predicted that production of high molecular mass
      catestatin intermediates requires cleavage at the COOH-terminal sides of paired
      basic residues, which is compatible with the cleavage specificities of PC1 and
      PC2 prohormone convertases. However, it is notable that production of catestatin
      itself (CgA(344)(-)(364)) utilizes more unusual cleavage sites at the NH(2)
      terminal sides of downward arrow R and downward arrow RR basic residue sites,
      consistent with the cleavage specificities of the chromaffin granule cysteine
      protease "PTP" that participates in proenkephalin processing. These findings
      demonstrate that production of catestatin involves cleavage of CgA at paired
      basic and monobasic residues, necessary steps for catestatin peptide regulation
      of nicotinic cholinergic-induced catecholamine release.

PMID- 12795590
TI  - Nativelike intermediate on the unfolding pathway of pig kidney fructose-1,6
      bisphosphatase.
AB  - The unfolding and dissociation of the tetrameric enzyme fructose-1,6
      bisphosphatase from pig kidney by guanidine hydrochloride have been investigated
      at equilibrium by monitoring enzyme activity, ANS binding, intrinsic (tyrosine)
      protein fluorescence, exposure of thiol groups, fluorescence of extrinsic probes
      (AEDANS, MIANS), and size-exclusion chromatography. The unfolding is a multistate
      process involving as the first intermediate a catalytically inactive tetramer.
      The evidence that indicates the existence of this intermediate is as follows: (1)
      the loss of enzymatic activity and the concomitant increase of ANS binding, at
      low concentrations of Gdn.HCl (midpoint at 0.75 M), are both protein
      concentration independent, and (2) the enzyme remains in a tetrameric state at
      0.9 M Gdn.HCl as shown by size-exclusion chromatography. At slightly higher
      Gdn.HCl concentrations the inactive tetramer dissociates to a compact dimer which
      is prone to aggregate. Further evidence for dissociation of tetramers to dimers
      and of dimers to monomers comes from the concentration dependence of AEDANS
      labeled enzyme anisotropy data. Above 2.3 M Gdn.HCl the change of AEDANS
      anisotropy is concentration independent, indicative of monomer unfolding, which
      also is detected by a red shift of MIANS-labeled enzyme emission. At Gdn.HCl
      concentrations higher than 3.0 M, the protein elutes from the size-exclusion
      column as a single peak, with a retention volume smaller than that of the native
      protein, corresponding to the completely unfolded monomer. In the presence of its
      cofactor Mg(2+), the denaturated enzyme could be successfully reconstituted into
      the active enzyme with a yield of approximately 70-90%. Refolding kinetic data
      indicate that rapid refolding and reassociation of the monomers into a nativelike
      tetramer and reactivation of the tetramer are sequential events, the latter
      involving slow and small conformational rearrangements in the refolded enzyme.

PMID- 12795591
TI  - Epitope-dependent blocking of the angiotensin-converting enzyme dimerization by
      monoclonal antibodies to the N-terminal domain of ACE: possible link of ACE
      dimerization and shedding from the cell surface.
AB  - In a biomembrane modeling system, reverse micelles, somatic ACE forms dimers via
      carbohydrate-mediated interaction, providing evidence for the existence of a
      carbohydrate-recognizing domain on the ACE molecule. We localized this putative
      region on the N-domain of ACE using monoclonal antibodies (mAbs) to seven
      different epitopes of ACE. Two mAbs, 9B9 and 3G8, directed to distinct, but
      overlapping, epitopes of the N-domain of ACE shielded the CRD. Only "simple" ACE
      antibody complexes were found in the system. Five mAbs allowed the formation of
      "double" antibody-ACE-ACE-antibody complexes via carbohydrate-mediated
      interactions. The results were confirmed using the ACE N- and C-domains.
      Testicular ACE was unable to form carbohydrate-mediated ACE dimers in the reverse
      micelles, while the N-domain of ACE, obtained by limited proteolysis of the
      parent full-length ACE, retained the ability to form dimers. Furthermore, mAb
      3G8, which blocked ACE dimerization in micelles, significantly inhibited ACE
      shedding from the surface of ACE-expressing cells. Galactose prevented ACE
      dimerization in reverse micelles and also affected antibody-induced ACE shedding
      in an epitope-dependent manner. Restricted glycosylation of somatic ACE, obtained
      by the treatment of CHO-ACE cells with the glucosidase inhibitor N
      butyldeoxynojirimycin, significantly increased the rate of basal ACE shedding and
      altered antibody-induced ACE shedding. A chemical cross-linking approach was used
      to show that ACE is present (at least in part) as noncovalently linked dimers on
      the surface of CHO-ACE cells. These results suggest a possible link between
      putative ACE dimerization on the cell surface and the proteolytic cleavage
      (shedding) of ACE.

PMID- 12795592
TI  - Mechanism of low-density lipoprotein oxidation by hemoglobin-derived iron.
AB  - Excellular hemoglobin is an extremely active oxidant of low-density lipoproteins
      (LDL), a phenomenon explained so far by different mechanisms. In this study, we
      analyzed the mechanism of met-hemoglobin oxidability by comparing its mode of
      operation with other hemoproteins, met-myoglobin and horseradish peroxidase (HRP)
      or with free hemin. The kinetics of met-hemoglobin activity toward LDL lipids and
      protein differed from that of met-myoglobin and HRP, both quantitatively and
      qualitatively. Those differences were further clarified by analyzing heme
      transfer from the above-mentioned hemoproteins to LDL. It appeared that met
      hemoglobin transferred most of its hemin to LDL, and the presence of H(2)O(2)
      accelerated the process. In contrast, met-myoglobin partially released hemin, but
      only in the presence of H(2)O(2), while HRP could not transfer heme at all. The
      minor amount of hemin transferred from met-myoglobin to LDL sufficed to trigger
      ApoB oxidation, forming covalent aggregates via inter-bityrosines. This indicated
      that heme bound to high affinity site(s) is responsible for oxidation. LDL
      components providing the sites were analyzed by binding heme-CO monomers to LDL.
      Soret spectra revealed that the high affinity site of monomeric hemin is located
      on the LDL protein, ApoB. The complex heme-CO-ApoB underwent instantaneous
      oxidation to hemin-ApoB, and the bound hemin then slowly disintegrated in
      conjunction with LDL oxidation. Hemopexin prevented LDL oxidation by trapping
      hemoprotein transferable heme. We concluded that met-hemoglobin exerts its
      oxidative activity on LDL via transfer of heme, which serves as a vehicle for
      iron insertion into the LDL protein, leading to formation of atherogenic LDL
      aggregates.

PMID- 12795593
TI  - Identification of the catalytic residues of AroA (Enolpyruvylshikimate 3
      phosphate synthase) using partitioning analysis.
AB  - AroA (EPSP synthase) catalyzes carboxyvinyl transfer through addition of
      shikimate 3-phosphate (S3P) to phosphoenolpyruvate (PEP) to form a tetrahedral
      intermediate (THI), followed by phosphate elimination to give
      enolpyruvylshikimate 3-phosphate (EPSP). A novel approach, partitioning analysis,
      was used to elucidate the roles of catalytic residues in each step of the
      reaction. Partitioning analysis involved trapping and purifying [1-(14)C]THI,
      degrading it with AroA, and quantitating the products. Wild-type AroA gave a
      partitioning factor, f(PEP) = 0.25 +/- 0.02 at pH 7.5, where f(PEP) = [[1
      (14)C]PEP]/([[1-(14)C]PEP] + [[1-(14)C]EPSP]). Eighteen mutations were made to 14
      amino acids to discover which residues preferentially catalyzed either the
      addition or the elimination step. Mutating a residue catalyzing one step (e.g.,
      addition) should change f(PEP) to favor the opposite step (e.g., elimination). No
      mutants caused large changes in f(PEP), with experimental values from 0.07 to
      0.41. This implied that there are no side chains that catalyze only addition or
      elimination, which further implied that the same residues are general acid/base
      catalysts in both forward and reverse THI breakdown. Only Lys22 (protonating S3P
      hydroxyl or phosphate) and Glu341 (deprotonating C3 of PEP) are correctly
      situated in the active site. In the overall reaction, Lys22 would act as a
      general base during addition, while Glu341 would act as a general acid. Almost
      half of the mutations (eight of 18) caused a >1000-fold decrease in specific
      activity, demonstrating that a large number of residues are important for
      transition state stabilization, "ensemble catalysis", in contrast to some enzymes
      where a single amino acid can be responsible for up to 10(8)-fold catalytic
      enhancement.

PMID- 12795594
TI  - Reaction mechanism of the heterotetrameric (alpha2beta2) E1 component of 2-oxo
      acid dehydrogenase multienzyme complexes.
AB  - Pyruvate decarboxylase (E1) catalyzes the first two reactions of the four
      involved in oxidative decarboxylation of pyruvate by the pyruvate dehydrogenase
      (PDH) multienzyme complex. It requires thiamin diphosphate to bring about the
      decarboxylation of pyruvate, which is followed by the reductive acetylation of a
      lipoyl group covalently bound to the N(6) amino group of a lysine residue in the
      second catalytic component, a dihydrolipoyl acetyltransferase (E2). Replacement
      of two histidine residues in the E1alpha and E1beta chains of the
      heterotetrameric E1 (alpha(2)beta(2)) component of the PDH complex of Bacillus
      stearothermophilus, considered possible proton donors at the active site, was
      carried out. Subsequent characterization of the mutants permitted different roles
      to be assigned to these two particular residues in the reaction catalyzed by E1:
      E1alpha His271 to stabilize the dianion formed during decarboxylation of the 2
      oxo acid and E1beta His128 to provide the proton required to protonate the
      incoming dithiolane ring in the subsequent reductive acetylation of the lipoyl
      goup. On the basis of these and other results from a separate investigation into
      the roles of individual residues in a loop region in the E1alpha chain close to
      the active site of E1 [Fries, M., Chauhan, H. J., Domingo, G. J., Jung, H., and
      Perham, R. N. (2002) Eur. J. Biochem. 270, 861-870] together with work from other
      laboratories, a detailed mechanism for the E1 reaction can be formulated.

PMID- 12795595
TI  - Toward understanding the mechanism of the complex cyclization reaction catalyzed
      by imidazole glycerolphosphate synthase: crystal structures of a ternary complex
      and the free enzyme.
AB  - Imidazole glycerol phosphate synthase catalyzes formation of the imidazole ring
      in histidine biosynthesis. The enzyme is also a glutamine amidotransferase, which
      produces ammonia in a glutaminase active site and channels it through a 30-A
      internal tunnel to a cyclase active site. Glutaminase activity is impaired in the
      resting enzyme, and stimulated by substrate binding in the cyclase active site.
      The signaling mechanism was investigated in the crystal structure of a ternary
      complex in which the glutaminase active site was inactivated by a glutamine
      analogue and the unstable cyclase substrate was cryo-trapped in the active site.
      The orientation of N(1)-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4
      carboxamide ribonucleotide in the cyclase active site implicates one side of the
      cyclase domain in signaling to the glutaminase domain. This side of the cyclase
      domain contains the interdomain hinge. Two interdomain hydrogen bonds, which do
      not exist in more open forms of the enzyme, are proposed as molecular signals.
      One hydrogen bond connects the cyclase domain to the substrate analogue in the
      glutaminase active site. The second hydrogen bond connects to a peptide that
      forms an oxyanion hole for stabilization of transient negative charge during
      glutamine hydrolysis. Peptide rearrangement induced by a fully closed domain
      interface is proposed to activate the glutaminase by unblocking the oxyanion
      hole. This interpretation is consistent with biochemical results [Myers, R. S.,
      et al., (2003) Biochemistry 42, 7013-7022, the accompanying paper in this issue]
      and with structures of the free enzyme and a binary complex with a second
      glutamine analogue.

PMID- 12795596
TI  - Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate
      synthase.
AB  - IGP synthase is a glutamine amidotransferase that incorporates ammonia derived
      from glutamine into the unusual nucleotide, N(1)-[(5'-phosphoribulosyl)
      formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR) to form 5'-(5
      aminoimidazole-4-carboxamide) ribonucleotide (AICAR) and imidazole glycerol
      phosphate (IGP). A common feature of all glutamine amidotransferases is the
      upregulation of glutamine hydrolysis in the presence of an acceptor substrate. A
      refined assay system was developed to establish that Saccharomyces cerevisae IGP
      synthase shows a 4900-fold stimulation of glutaminase in the presence of the
      substrate acceptor PRFAR. The structure and function of IGP synthase acceptor
      substrate binding site were probed with competitive inhibitors that are
      nucleotide substrate and product analogues. In addition, these analogues were
      also used to establish that the normal steady-state turnover cycle involves a
      random sequential mechanism. Upregulation of the glutaminase active site occurs
      when these competitive inhibitors bind in the nucleotide site over 30 A away. One
      of the key structural features of IGP synthase is that the transfer of ammonia
      from the glutaminase site occurs through the (beta/alpha)(8) core of the protein.
      Upon the basis of the recent substrate-occupied structure for yeast IGP synthase
      (1), kinetic investigations of site-directed mutants revealed that a conserved
      K258 residue is key to productive binding and the overall stoichiometry of the
      reaction. The binding of the ribulosyl phosphate portion of the substrate PRFAR
      appears to be transduced through reorientation of K258 resulting in a
      conformational switch at the base of the (beta/alpha)(8) core that enables the
      passage of ammonia through the core of the protein. The overall analysis also
      leads to further discussion of how the residues that cover the opening of the
      (beta/alpha)(8) in the closed state may assist the channeling of ammonia at the
      interface of the two functional domains in the open state.

PMID- 12795597
TI  - Wobble dC.dA pairing 5' to the cationic guanine N7 8,9-dihydro-8-(N7-guanyl)-9
      hydroxyaflatoxin B1 adduct: implications for nontargeted AFB1 mutagenesis.
AB  - The structure of 5'-d(ACATC(AFB)GATCT)-3'.5'-d(AGATCAATGT)-3', containing the
      C(5).A(16) mismatch at the base pair 5' to the modified (AFB)G(6), was determined
      by NMR. The characteristic 5'-intercalation of the AFB(1) moiety was maintained.
      The mismatched C(5).A(16) pair existed in the wobble conformation, with the C(5)
      imino nitrogen hydrogen bonded to the A(16) exocyclic amino group. The wobble
      pair existed as a mixture of protonated and nonprotonated species. The pK(a) for
      protonation at the A(16) imino nitrogen was similar to that of the C(5).A(16)
      wobble pair in the corresponding duplex not adducted with AFB(1). Overall, the
      presence of AFB(1) did not interfere with wobble pair formation at the mismatched
      site. Molecular dynamics calculations restrained by distances derived from NOE
      data and torsion angles derived from (1)H (3)J couplings were carried out for
      both the protonated and nonprotonated wobble pairs at C(5).A(16). Both sets of
      calculations predicted the A(16) amino group was within 3 A of the C(5) imino
      nitrogen. The calculations suggested that protonation of the C(5).A(16) wobble
      pair should shift C(5) toward the major groove and shift A(16) toward the minor
      groove. The NMR data showed evidence for the presence of a minor conformation
      characterized by unusual NOEs between T(4) and (AFB)G(6). T(4) is two nucleotides
      in the 5'-direction from the modified base. These NOEs suggested that in the
      minor conformation nucleotide T(4) was in closer proximity to (AFB)G(6) than
      would be expected for duplex DNA. Modeling studies examined the possibility that
      T(4) transiently paired with the mismatched A(16), allowing it to come within NOE
      distance of (AFB)G(6). This model structure was consistent with the unusual NOEs
      associated with the minor conformation. The structural studies are discussed in
      relationship to nontargeted C --> T transitions observed 5' to the modified
      (AFB)G in site-specific mutagenesis experiments [Bailey, E. A., Iyer, R. S.,
      Stone, M. P., Harris, T. M., and Essigmann, J. M. (1996) Proc. Natl. Acad. Sci.
      U.S.A. 93, 1535-1539].

PMID- 12795598
TI  - Functional characterization of transgene integration patterns by halo
      fluorescence in situ hybridization: electroporation versus retroviral infection.
AB  - Gene transfer techniques are essential for bioengineering and gene therapy.
      Retroviral vectors constitute an important tool in this context as integrase
      catalyzed genomic anchoring is one of the best defined results of nonhomologous
      recombination, occurring at loci with favorable expression properties. On the
      basis of a retroviral expression cassette, this study focuses on differences
      regarding the genomic targets after its transfer by either retroviral infection
      or electroporation. Fluorescence in situ hybridization (FISH) of clones generated
      by infection revealed for the majority an association of the transgene with the
      nuclear matrix while this was true only for a minority of single copy clones if
      the same construct was transferred by electroporation. Our results demonstrate
      that the process of integration is distinct for both gene transfer routes and
      confirm that retroviral survival strategies favor integration next to
      scaffold/matrix attachment regions. These results may be one key to explain
      recent consequences of gene therapy trials that have led to the deregulation of
      endogenous genes.

PMID- 12795599
TI  - Contribution to stability and folding of a buried polar residue at the CARM1
      methylation site of the KIX domain of CBP.
AB  - The transcriptional coactivator and acetyltransferase CREB Binding Protein (CBP)
      is comprised of several autonomously folded and functionally independent domains.
      The KIX domain mediates interactions between CBP and numerous transcriptional
      activators. The folded region of KIX has all the structural features of a
      globular protein, including three alpha-helices, two short 3(10) helices, and a
      well-packed hydrophobic core. KIX contains a buried cation-pi interaction between
      the positively charged guanidinium group of Arg 600 and the aromatic ring of Tyr
      640. Arg 600 is a site for regulatory methylation by CARM1/PRMT4, which negates
      the CREB-binding function of the KIX domain. The role of the Arg 600-Tyr 640
      buried polar interaction in specifying and stabilizing the structure of KIX was
      investigated by comparing the folding of wild-type KIX with the single point
      mutants Y640F and R600M. The Y640F mutant disrupts a hydrogen bond involving the
      Tyr 640 OH and the backbone of V595 but still allows for the cation-pi
      interaction while the R600M mutant disrupts the cation-pi interaction. Both wild
      type KIX and Y640F exhibit properties expected of native like, globular proteins
      such as a single oligomerization state (monomer), cooperative thermal and urea
      induced unfolding transitions, and a well-packed core. In contrast, the R600M
      mutant has properties reminiscent of a molten globule state, including a tendency
      to aggregate, noncooperative thermal unfolding transition, and a loosely packed
      core. Thus, the buried cation-pi interaction is critical for specifying the
      unique cooperatively folded structure of KIX.

PMID- 12795600
TI  - Surface salt bridges, double-mutant cycles, and protein stability: an
      experimental and computational analysis of the interaction of the Asp 23 side
      chain with the N-terminus of the N-terminal domain of the ribosomal protein l9.
AB  - Experimental and theoretical double-mutant cycles have been used to investigate a
      salt bridge in the N-terminal domain of the protein L9. Aspartic acid 23 is the
      only acidic residue involved in a well-defined pairwise interaction, namely, a
      partially solvent-exposed salt bridge with the protonated N-terminus of the
      protein. Mutations were studied in which Asp 23 was substituted by alanine,
      asparagine, and nitrile alanine. Interactions with the N-terminus were probed by
      comparisons between proteins with a protonated and acetylated N-terminus. The
      mutants were all folded, and the structures were unchanged from wild type as
      judged by CD and 2-D NMR. The coupling free energy between the N-terminus and the
      side chain of Asp 23 measured through double-mutant cycle analysis was favorable
      and ranged from -0.7 to -1.7 kcal mol(-)(1), depending upon the set of mutants
      used. This relatively large coupling free energy for a surface salt bridge likely
      arises from geometric factors that reduce the entropy loss associated with salt
      bridge formation and from structural relaxation in the mutants. Coupling free
      energies computed with continuum electrostatic calculations agreed well with the
      experimental values when full account was taken of all potential interactions,
      particularly those involving Asp 23 and the acetylated N-terminus as well as
      interactions with solvent. The measured and calculated coupling free energy
      decreased only slightly when the salt concentration was increased from 100 to 750
      mM NaCl. The calculations suggest that the coupling free energy between D23 and
      the N-terminus measured through the experimental double-mutant cycle analysis is
      significantly smaller than the actual interaction free energy between the groups
      in the wild-type structure because of the inapplicability of assumptions
      frequently used to interpret double-mutant cycles.

PMID- 12795601
TI  - Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module
      from human Notch1.
AB  - Notch1 is a member of a conserved family of large modular heterodimeric type 1
      transmembrane receptors that control differentiation in multicellular animals.
      Receptor maturation is accompanied by a furin-dependent cleavage that converts
      the Notch1 precursor polypeptide into a heterodimer consisting of an
      extracellular ligand-binding subunit (NEC) and a transmembrane signaling subunit
      (NTM). Binding of a physiologic ligand to NEC induces signaling by triggering
      additional proteolytic cleavages in NTM, which allow its intracellular region to
      translocate to the nucleus where it participates in a transcriptional activation
      complex. In the absence of ligand, the three conserved LNR modules of the NEC
      subunit participate in maintaining the receptor in its resting conformation.
      Here, we report the solution structure of the first LNR module (LNR_A) of human
      Notch1, and identify residues of LNR_A perturbed by the presence of the adjacent
      module LNR_B. LNR_A is held together by a unique arrangement of three disulfide
      bonds and a single bound Ca(2+) ion, and adopts a novel fold that falls in the
      general class of irregular disulfide-bonded structures. Residues perturbed by the
      presence of the adjacent LNR_B module are predominantly hydrophobic, and lie on
      one face of the module. These studies represent an initial step toward
      understanding the structural interrelationships among the three contiguous LNR
      modules required for proper regulation of Notch signaling.

PMID- 12795602
TI  - Transient protein interactions studied by NMR spectroscopy: the case of
      cytochrome C and adrenodoxin.
AB  - The interaction between yeast iso-1-cytochrome c (C102T) and two forms of bovine
      adrenodoxin, the wild type and a truncated form comprising residues 4-108, has
      been investigated using a combination of one- and two-dimensional heteronuclear
      NMR spectroscopy. Chemical shift perturbations and line broadening of amide
      resonances in the [(15)N,(1)H]HSQC spectrum for both (15)N-labeled cytochrome c
      and adrenodoxin in the presence of the unlabeled partner protein indicate the
      formation of a transient complex, with a K(a) of (4 +/- 1) x 10(4) M(-)(1) and a
      lifetime of <3 ms. The perturbed residues map over a large surface area for both
      proteins. For cytochrome c, the dominating effects are located around the exposed
      heme edge but with other areas also affected upon formation of the complex. In
      the case of adrenodoxin, effects are seen in both the recognition and core
      domains, with the largest perturbations in the recognition domain. These results
      indicate that the complex has a dynamic nature, with delocalized binding of
      cytochrome c on adrenodoxin. A comparison with other transient complexes of redox
      proteins places this complex between well-defined complexes such as the
      cytochrome c-cytochrome c peroxidase complex and entirely dynamic complexes such
      as the cytochrome b(5)-myoglobin complex.

PMID- 12795603
TI  - Redesigning an antibody fragment for faster association with its antigen.
AB  - Traditional approaches for increasing the affinity of protein-protein complexes
      focus on constructing highly complementary binding surfaces. Recent theoretical
      simulations and experimental results suggest that electrostatic steering forces
      can also be manipulated to increase association rates while leaving dissociation
      rates unchanged, thus increasing affinity. Here we demonstrate that electrostatic
      attraction can be enhanced between an antibody fragment and its cognate antigen
      through application of a few simple rules to identify potential on-rate
      amplification sites that lie at the periphery of the antigen-antibody interface.

PMID- 12795604
TI  - Structural and functional consequences of binding site mutations in transferrin:
      crystal structures of the Asp63Glu and Arg124Ala mutants of the N-lobe of human
      transferrin.
AB  - Human transferrin is a serum protein whose function is to bind Fe(3+) with very
      high affinity and transport it to cells, for delivery by receptor-mediated
      endocytosis. Structurally, the transferrin molecule is folded into two globular
      lobes, representing its N-terminal and C-terminal halves, with each lobe
      possessing a high-affinity iron binding site, in a cleft between two domains.
      Central to function is a highly conserved set of iron ligands, including an
      aspartate residue (Asp63 in the N-lobe) that also hydrogen bonds between the two
      domains and an arginine residue (Arg124 in the N-lobe) that binds an iron-bound
      carbonate ion. To further probe the roles of these residues, we have determined
      the crystal structures of the D63E and R124A mutants of the N-terminal half
      molecule of human transferrin. The structure of the D63E mutant, determined at
      1.9 A resolution (R = 0.245, R(free) = 0.261), showed that the carboxyl group
      still binds to iron despite the larger size of the Glu side chain, with some
      slight rearrangement of the first turn of alpha-helix residues 63-72, to which it
      is attached. The structure of the R124A mutant, determined at 2.4 A resolution (R
      = 0.219, R(free) = 0.288), shows that the loss of the arginine side chain results
      in a 0.3 A displacement of the carbonate ion, and an accompanying movement of the
      iron atom. In both mutants, the iron coordination is changed slightly, the
      principal change being in each case a lengthening of the Fe-N(His249) bond. Both
      mutants also release iron more readily than the wild type, kinetically and in
      terms of acid lability of iron binding. We attribute this to more facile
      protonation of the synergistically bound carbonate ion, in the case of R124A, and
      to strain resulting from the accommodation of the larger Glu side chain, in the
      case of D63E. In both cases, the weakened Fe-N(His) bond may also contribute,
      consistent with protonation of the His ligand being an early intermediate step in
      iron release, following the protonation of the carbonate ion.

PMID- 12795605
TI  - Chain length dependence of apomyoglobin folding: structural evolution from
      misfolded sheets to native helices.
AB  - Very little is known about how protein structure evolves during the polypeptide
      chain elongation that accompanies cotranslational protein folding. This in vitro
      model study is aimed at probing how conformational space evolves for purified N
      terminal polypeptides of increasing length. These peptides are derived from the
      sequence of an all-alpha-helical single domain protein, Sperm whale apomyoglobin
      (apoMb). Even at short chain lengths, ordered structure is found. The nature of
      this structure is strongly chain length dependent. At relatively short lengths, a
      predominantly non-native beta-sheet conformation is present, and self-associated
      amyloid-like species are generated. As chain length increases, alpha-helix
      progressively takes over, and it replaces the beta-strand. The observed trends
      correlate with the specific fraction of solvent-accessible nonpolar surface area
      present at different chain lengths. The C-terminal portion of the chain plays an
      important role by promoting a large and cooperative overall increase in helical
      content and by consolidating the monomeric association state of the full-length
      protein. Thus, a native-like energy landscape develops late during apoMb chain
      elongation. This effect may provide an important driving force for chain
      expulsion from the ribosome and promote nearly-posttranslational folding of
      single domain proteins in the cell. Nature has been able to overcome the above
      intrinsic misfolding trends by modulating the composition of the intracellular
      environment. An imbalance or improper functioning by the above modulating factors
      during translation may play a role in misfolding-driven intracellular disorders.

PMID- 12795606
TI  - Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase.
AB  - Crystal structures of many enzymes in the aldehyde dehydrogenase superfamily
      determined in the presence of bound NAD(P)(+) have exhibited conformational
      flexibility for the nicotinamide half of the cofactor. This has been hypothesized
      to be important in catalysis because one conformation would block the second half
      of the reaction, but no firm evidence has been put forth which shows whether the
      oxidized and reduced cofactors preferentially occupy the two observed
      conformations. We present here two structures of the wild type and two structures
      of a Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase in binary
      complexes with NAD(+) and NADH. These structures, including the Cys302Ser mutant
      in complex with NAD(+) at 1.4 A resolution and the wild-type enzyme in complex
      with NADH at 1.9 A resolution, provide strong evidence that bound NAD(+) prefers
      an extended conformation ideal for hydride transfer and bound NADH prefers a
      contracted conformation ideal for acyl-enzyme hydrolysis. Unique interactions
      between the cofactor and the Rossmann fold make isomerization possible while
      allowing the remainder of the active site complex to remain intact. In addition,
      these structures clarify the role of magnesium in activating the human class 2
      enzyme. Our data suggest that the presence of magnesium may lead to selection of
      particular conformations and speed isomerization of the reduced cofactor
      following hydride transfer.

PMID- 12795607
TI  - Localization of phospho-beta-dystroglycan (pY892) to an intracellular vesicular
      compartment in cultured cells and skeletal muscle fibers in vivo.
AB  - beta-Dystroglycan is a ubiquitously expressed integral membrane protein that
      undergoes tyrosine phosphorylation in an adhesion-dependent manner. Tyrosine 892
      is now thought to be the principal site for recognition by the c-Src tyrosine
      kinase; however, little is known about the regulation of this phosphorylation
      event in vivo. Here, we generated a novel monoclonal antibody probe that
      recognizes only tyrosine 892 phosphorylated beta-dystroglycan (pY892). We show
      that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change
      in its sub-cellular localization (e.g., from the plasma membrane to an internal
      membrane compartment). One possibility is that the net negative charge at
      position 892 causes the redistribution of beta-dystroglycan to this intracellular
      vesicular location. In support of this notion, mutation of tyrosine 892 to
      glutamate (Y892E) is sufficient to drive this intracellular localization, while
      other point mutants (Y892F and Y892A) remain at the plasma membrane.
      Interestingly, our colocalization studies with endosomal markers (EEA1,
      transferrin, and transferrin receptor) suggest that these phospho-beta
      dystroglycan containing internal vesicles represent a subset of recycling
      endosomes. At the level of these internal vesicular structures, we find that
      tyrosine phosphorylated beta-dystroglycan is colocalized with c-Src. In addition,
      we demonstrate that known ligands for alpha-dystroglycan, namely, agrin and
      laminin, are able to induce the tyrosine phosphorylation of beta-dystroglycan.
      Finally, we show that tyrosine phosphorylated beta-dystroglycan is also
      detectable in skeletal muscle tissue lysates and is localized to an internal
      vesicular membrane compartment in skeletal muscle fibers in vivo. The generation
      of a phospho-specific beta-dystroglycan (pY892) mAb probe provides a new powerful
      tool for dissecting the role of dystroglycan phosphorylation in normal cellular
      functioning and in the pathogenesis of muscular dystrophies.

PMID- 12795608
TI  - Intrinsic tyrosine fluorescence as a tool to study the interaction of the shaker
      B "ball" peptide with anionic membranes.
AB  - Steady-state and time-resolved fluorescence from the single tyrosine in the
      inactivating peptide of the Shaker B potassium channel (ShB peptide) and in a
      noninactivating peptide mutant, ShB-L7E, has been used to characterize their
      interaction with anionic phospholipid membranes, a model target mimicking
      features of the inactivation site on the channel protein. Partition coefficients
      derived from steady-state anisotropy indicate that both peptides show a high
      affinity for anionic vesicles, being higher in ShB than in ShB-L7E. Moreover,
      differential quenching by lipophilic spin-labeled probes and fluorescence energy
      transfer using trans-parinaric acid as the acceptor confirm that the ShB peptide
      inserts deep into the membrane, while the ShB-L7E peptide remains near the
      membrane surface. The rotational mobility of tyrosine in membrane-embedded ShB,
      examined from the decay of fluorescence anisotropy, can be described by two
      different rotational correlation times and a residual constant value. The short
      correlation time corresponds to fast rotation reporting on local tyrosine
      mobility. The long rotational correlation time and the high residual anisotropy
      suggest that the ShB peptide diffuses in a viscous and anisotropic medium
      compatible with the aliphatic region of a lipid bilayer and support the
      hypothesis that the peptide inserts into it as a monomer, to configure an
      intramolecular beta-hairpin structure. Assuming that this hairpin structure
      behaves like a rigid body, we have estimated its dimensions and rotational
      dynamics, and a model for the peptide inserted into the bilayer has been
      proposed.

PMID- 12795609
TI  - Mechanistic investigation of peptidylglycine alpha-hydroxylating monooxygenase
      via intrinsic tryptophan fluorescence and mutagenesis.
AB  - The biosynthesis of the majority of biologically active peptides ends with an
      obligatory alpha-amidation step that is catalyzed only by peptidylglycine alpha
      hydroxylating monooxygenase (PHM). The utility of two mechanisms proposed for
      this copper- and ascorbate-dependent monooxygenase was examined using site
      directed mutagenesis and intrinsic tryptophan fluorescence. Retention of full
      activity by PHMccGln(170)Ala and -Asn eliminates a critical role for Gln(170) in
      a substrate-mediated electron transfer pathway. The 20-fold reduction in V(max)
      observed for PHMccGln(170)Glu and -Leu is consistent with a key role for
      conformational changes in this region. Mutation of Tyr(79), situated near Cu(A),
      to Trp reduced V(max) 200-fold. Measurement of changes in intrinsic fluorescence
      allowed determination of a K(d) for copper (0.06 microM) and for a
      peptidylglycine substrate, Phe-Gly-Phe-Gly (0.8 microM). Although the
      peptidylglycine substrate bound more tightly at pH 7.0 than at pH 5.5, V(max)
      decreased 25-fold at neutral pH. Total quenching of the signal from Trp(79) in
      apoPHMccTyr(79)Trp along with its greatly reduced V(max) defines a critical role
      for Cu(A) in the rate-limiting step of the reaction. Taking into account our data
      and the results of kinetic, spectroscopic, and crystallographic studies, we
      propose a mechanism in which substrate-mediated activation of molecular oxygen
      binding at Cu(A) completes a pathway for electron transfer from Cu(B).

PMID- 12795610
TI  - Evidence for the two phosphate binding sites of an analogue of the thioacyl
      intermediate for the Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase
      catalyzed reaction, from its crystal structure.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the reversible
      oxidative phosphorylation of d-glyceraldehyde 3-phosphate (GAP) into d-glycerate
      1,3-bisphosphate (1,3-diPG) in the presence of NAD(+) and inorganic phosphate
      (P(i)). Within the active site, two anion-binding sites were ascribed to the
      binding of the C3 phosphate of GAP (P(s)) and to the binding of the attacking
      phosphate ion (P(i)). The role played by these two sites in the catalytic
      mechanism in connection with the functional role of coenzyme exchange (NADH
      NAD(+) shuttle) has been investigated by several studies leading to the C3
      phosphate flipping model proposed by Skarzynski et al. [Skarzynski, T., Moody, P.
      C., and Wonacott, A. J. (1987) J. Mol. Biol. 193, 171-187]. This model has not
      yet received direct confirmation. To gain further insight into the role of both
      sites, we synthesized irreversible inhibitors which form with the essential
      cysteine residue a thioacyl enzyme analogue of the catalytic intermediate. Here
      we report the refined glycosomal Trypanosoma cruzi GAPDH in complex with a
      covalently bound GAP analogue at an improved resolution of 2.0-2.5 A. For this
      holo-thioacyl enzyme complex, a flip-flop movement is clearly characterized, the
      change from the P(i) to the P(s) binding site being correlated with the coenzyme
      exchange step: the weaker interaction of the intermediate when bound at the P(s)
      site with the cofactor allows its release and also the binding of the inorganic
      phosphate for the next catalytic step. This result gives strong experimental
      support for the generally accepted flip-flop model of the catalytic mechanism in
      GAPDH.

PMID- 12795611
TI  - A lead-dependent DNAzyme with a two-step mechanism.
AB  - A detailed biochemical and mechanistic study of in vitro selected variants of 8
      17 DNAzymes is presented. Even though the 8-17 DNAzyme motif has been obtained
      through in vitro selection under three different conditions involving 10 mM
      Mg(2+) (called 8-17), 0.5 mM Mg(2+)/50 mM histidine (called Mg5), or 100 microM
      Zn(2+) (called 17E), all variants are shown to be the most active with Pb(2+) (8
      17: k(obs) approximately 0.5 min(-1); Mg5: k(obs) approximately 2 min(-1); 17E:
      k(obs) approximately 1 min(-1) with 200 microM Pb(2+) at pH 5.0). For the 17E
      variant of the 8-17 DNAzyme, the single-turnover rate constants followed the
      order of Pb(2+) >> Zn(2+) >> Mn(2+) approximately Co(2+) > Ni(2+) > Mg(2+)
      approximately Ca(2+) > Sr(2+) approximately Ba(2+). The catalytic rate is half
      maximal at 13.5 microM Pb(2+), 0.97 mM Zn(2+), or 10.5 mM Mg(2+), suggesting that
      the metal-binding affinity of the DNAzymes is in the order of Pb(2+) > Zn(2+) >
      Mg(2+). The Pb(2+)-dependent activity increases linearly with pH and the slope of
      the plot of log k(obs) versus pH is approximately 1, suggesting a single
      deprotonation in the rate-limiting step of the reaction. Sequence variations of
      the DNAzyme confirm the importance of the G*T wobble pair, the two loops and the
      intervening stem in maintaining the active conformation of the system. While
      Mg(2+) and Zn(2+) catalyze only a transesterification reaction with formation of
      a product containing a 2',3'-cyclic phosphate, Pb(2+) catalyzes a
      transesterification reaction followed by hydrolysis of the 2',3'-cyclic
      phosphate. Although this two-step mechanism has shown to be operative in protein
      ribonucleases and in the leadzyme RNAzyme, it is now demonstrated for the first
      time that this DNAzyme may also use the same mechanism. Therefore, the two-step
      mechanism is observed in metalloenzymes of all classes, and this 8-17 DNAzyme
      provides a simple, stable, and cost-effective model system for understanding the
      structure of Pb(2+)-binding sites and their roles in the two-step mechanism.

PMID- 12795612
TI  - Characterization of two forms of mouse salivary androgen-binding protein (ABP):
      implications for evolutionary relationships and ligand-binding function.
AB  - Mouse salivary androgen-binding protein (ABP) is a member of the secretoglobin
      family produced in the submaxillary glands of house mice (Mus musculus). We
      report the cDNA sequences and amino acid sequences of the beta and gamma subunits
      of ABP from a mouse cDNA library, identifying the two subunits by their pIs and
      molecular weights. An anomalously high molecular weight of the alpha subunit is
      likely due to glycosylation at a single site. A phylogenetic comparison of the
      three subunits of ABP with the chains of other mammalian secretoglobins shows
      that ABP is most closely related to mouse lachrymal protein and to the major cat
      allergen Fel dI. An evaluation of the most conserved residues in ABP and the
      other secretoglobins, in light of structural data reported by others [Callebaut,
      I., Poupon, A., Bally, R., Demaret, J.-P., Housset, D., Delettre, J., Hossenlopp,
      P., and Mornon, J.-P. (2000) Ann. N.Y. Acad. Sci. 923, 90-112; Pattabiraman, N.,
      Matthews, J., Ward, K., Mantile-Selvaggi, G., Miele, L., and Mukherjee, A. (2000)
      Ann. N.Y. Acad. Sci. 923, 113-127], allows us to draw conclusions about the
      critical residues important in ligand binding by the two different ABP dimers and
      to assess the importance of ligand binding in the function of the molecule. In
      addition to the cDNAs, which represent those of the musculus subspecies of Mus
      musculus, we also report the coding regions of the beta and gamma subunit cDNAs
      from two other mouse inbred strains which represent the other two subspecies: M.
      musculus domesticus and M. musculus castaneus. The high nonsynonymous/synonymous
      substitution rate ratios (K(a)/K(s)) for both the beta and gamma subunits suggest
      that these two proteins are evolving under strong directional selection, as has
      been reported for the alpha subunit [Hwang, J., Hofstetter, J., Bonhomme, F., and
      Karn, R. (1997) J. Hered. 88, 93-97; Karn, R., and Clements, M. (1999) Biochem.
      Genet. 37, 187-199].

PMID- 12795613
TI  - An in vitro assay using overexpressed yeast SRP demonstrates that cotranslational
      translocation is dependent upon the J-domain of Sec63p.
AB  - The signal recognition particle (SRP) is required for co-translational targeting
      of polypeptides to the endoplasmic reticulum (ER). Once at the membrane, the
      precursor interacts with a complex proteinaceous machinery that mediates its
      translocation across the bilayer. Genetic studies in yeast have identified a
      number of genes whose products are involved in this complex process. These
      mutants offer a potentially valuable resource with which to analyze the
      biochemical role played by each component in the pathway. However, such analyses
      have been hampered by the failure to reconstitute an efficient in vitro assay for
      SRP-dependent translocation. We report the construction of two multicopy vectors
      that allow overexpression of all seven gene products required to make SRP in the
      yeast Saccharomyces cerevisiae. The overexpressed subunits assemble into intact
      and functional SRP particles, and we further demonstrate that in vitro
      reconstitution of co-translational translocation is greatly enhanced using
      cytosol from the overexpression strain. We use this assay to demonstrate that
      Sec63p is required for co-translational translocation in vitro and specifically
      identify the "J-domain" of Sec63p as crucial for this pathway.

PMID- 12795615
TI  - Structural characterization and mapping of the covalently linked FAD cofactor in
      choline oxidase from Arthrobacter globiformis.
AB  - The flavoenzyme choline oxidase catalyzes the oxidation of choline and betaine
      aldehyde to betaine. Earlier studies have shown that the choline oxidase from
      Arthrobacter globiformis contains FAD covalently linked to a histidine residue.
      To identify the exact type of flavin binding, the FAD-carrying amino acid residue
      was released by acid hydrolysis. The fluorescence excitation maxima of the
      isolated aminoacylriboflavin, showing a hypsochromic shift of the near
      ultraviolet band relative to riboflavin, and the pH-dependent flavin fluorescence
      confirmed the presence of an 8alpha-substituted flavin linked to histidine.
      Similarly, MALDI-TOF mass spectrometry showed a molecular mass corresponding to
      histidylriboflavin. Classical experiments used to distinguish between the N(1)
      and N(3) isomers all indicated that the flavin was linked to the N(1) position of
      the histidine residue. The position of the FAD-carrying histidine residue in the
      choline oxidase polypeptide was identified by tryptic cleavage of the denatured
      enzyme, HPLC separation of the proteolytic peptide fragments, and
      characterization of the purified flavin-carrying peptide by mass spectrometry and
      spectroscopy. The FAD moiety was assigned to the tryptic peptide, His-Ala-Arg,
      corresponding to residues 87-89 in the open reading frame of the previously
      published cDNA sequence. Further analysis of the flavopeptide by collision
      induced dissociation mass spectrometry confirmed that the flavin cofactor was
      attached to His(87). We conclude that this variant of choline oxidase contains
      8alpha-[N(1)-histidyl]FAD at position 87 in the polypeptide chain.

PMID- 12795614
TI  - Mitogen-induced activation of Na+/H+ exchange in vascular smooth muscle cells
      involves janus kinase 2 and Ca2+/calmodulin.
AB  - The sodium/proton exchanger type 1 (NHE-1) plays an important role in the
      proliferation of vascular smooth muscle cells (VSMC). We have examined the
      regulation of NHE-1 by two potent mitogens, serotonin (5-HT, 5-hydroxytryptamine)
      and angiotensin II (Ang II), in cultured VSMC derived from rat aorta. 5-HT and
      Ang II rapidly activated NHE-1 via their G protein-coupled receptors (5-HT(2A)
      and AT(1)) as assessed by proton microphysiometry of quiescent cells and by
      measurements of intracellular pH on a FLIPR (fluorometric imaging plate reader).
      Activation of NHE-1 was blocked by inhibitors of phospholipase C, CaM, and Jak2
      but not by pertussis toxin or inhibitors of protein kinase C.
      Immunoprecipitation/immunoblot studies showed that 5-HT and Ang II induce
      phosphorylation of Jak2 and induce the formation of signal transduction complexes
      that included Jak2, CaM, and NHE-1. The cell-permeable Ca(2+) chelator BAPTA-AM
      blocked activation of Jak2, complex formation between Jak2 and CaM, and tyrosine
      phosphorylation of CaM, demonstrating that elevated intracellular Ca(2+) is
      essential for those events. Thus, mitogen-induced activation of NHE-1 in VSMC is
      dependent upon elevated intracellular Ca(2+) and is mediated by the Jak2
      dependent tyrosine phosphorylation of CaM and subsequent increased binding of CaM
      to NHE-1, similar to the pathway previously described for the bradykinin B(2)
      receptor in inner medullary collecting duct cells of the kidney [Mukhin, Y. V.,
      et al. (2001) J. Biol. Chem. 276, 17339-17346]. We propose that this pathway
      represents a fundamental mechanism for the rapid regulation of NHE-1 by G(q/11)
      protein-coupled receptors in multiple cell types.

PMID- 12795616
TI  - Mechanism, mutagenesis, and chemical rescue of a beta-mannosidase from
      cellulomonas fimi.
AB  - The chemical mechanism of a retaining beta-mannosidase from Cellulomonas fimi has
      been characterized through steady-state kinetic analyses with a range of
      substrates, coupled with chemical rescue studies on both the wild-type enzyme and
      mutants in which active site carboxyl groups have been replaced. Studies with a
      series of aryl beta-mannosides of vastly different reactivities (pK(a)(lg) = 4
      10) allowed kinetic isolation of the glycosylation and deglycosylation steps.
      Substrate inhibition was observed for all but the least reactive of these
      substrates. Bronsted analysis of k(cat) revealed a downward breaking plot
      (beta(lg) = -0.54 +/- 0.05) that is consistent with a change in rate-determining
      step (glycosylation to deglycosylation), and this was confirmed by partitioning
      studies with ethylene glycol. The pH dependence of k(cat)/K(m) follows an
      apparent single ionization of a group of pK(a) = 7.65 that must be protonated for
      catalysis. The tentative assignment of E429 as the acid-base catalyst of Man2A on
      the basis of sequence alignments with other family 2 glycosidases was confirmed
      by the increased turnover rate observed for the mutant E429A in the presence of
      azide and fluoride, leading to the production of beta-mannosyl azide and beta
      mannosyl fluoride, respectively. A pH-dependent chemical rescue of E429A activity
      is also observed with citrate. Substantial oxocarbenium ion character at the
      transition state was demonstrated by the alpha-deuterium kinetic isotope effect
      for Man2A E429A of alpha-D(V) = 1.12 +/- 0.01. Surprisingly, this isotope effect
      was substantially greater in the presence of azide (alpha-D(V) = 1.166 +/-
      0.009). Likely involvement of acid/base catalysis was revealed by the pH
      dependence of k(cat) for Man2A E429A, which follows a bell-shaped profile
      described by pK(a) values of 6.1 and 8.4, substantially different from that of
      the wild-type enzyme. The glycosidic bond cleaving activity of Man2A E519A and
      E519S nucleophile mutants is restored with azide and fluoride and appears to
      correlate with the corresponding "glycosynthase" activities. The contribution of
      the substrate 2-hydroxyl to stabilization of the Man2A glycosylation transition
      state (DeltaDeltaG() = 5.1 kcal mol(-1)) was probed using a 2-deoxymannose
      substrate. This value, surprisingly, is comparable to that found from equivalent
      studies with beta-glucosidases despite the geometric differences at C-2 and the
      importance of hydrogen bonding at that position. Modes of stabilizing the
      mannosidase transition state are discussed.

PMID- 12795617
TI  - Analysis of the cruciform binding activity of recombinant 14-3-3zeta-MBP fusion
      protein, its heterodimerization profile with endogenous 14-3-3 isoforms, and
      effect on mammalian DNA replication in vitro.
AB  - The human cruciform binding protein (CBP), a member of the 14-3-3 protein family,
      has been recently identified as an origin of DNA replication binding protein and
      involved in DNA replication. Here, pure recombinant 14-3-3zeta tagged with
      maltose binding protein (r14-3-3zeta-MBP) at its N-terminus was tested for
      binding to cruciform DNA either in the absence or presence of F(TH), a CBP
      enriched fraction, by electromobility shift assay (EMSA), followed by Western
      blot analysis of the electroeluted CBP-cruciform DNA complex. The r14-3-3zeta-MBP
      was found to have cruciform binding activity only after preincubation with F(TH).
      Anti-MBP antibody immunoprecipitation of F(TH) preincubated with r14-3-3zeta-MBP,
      followed by Western blot analysis with antibodies specific to the beta, gamma,
      epsilon, zeta, and sigma 14-3-3 isoforms showed that r14-3-3zeta-MBP
      heterodimerized with the endogenous beta, epsilon, and zeta isoforms present in
      the F(TH) but not with the gamma or sigma isoforms. Immunoprecipitation of
      endogenous 14-3-3zeta from nuclear extracts (NE) of HeLa cells that were either
      serum-starved (s-s) or blocked at the G(1)/S or G(2)/M phases of the cell cycle
      revealed that at G(1)/S and G(2)/M, the zeta isoform heterodimerized only with
      the beta and epsilon isoforms, while in s-s extracts, the 14-3-3zeta/epsilon
      heterodimer was never detected, and the 14-3-3zeta/beta heterodimer was seldom
      detected. Furthermore, addition of r14-3-3zeta-MBP to HeLa cell extracts used in
      a mammalian in vitro replication system increased the replication level of p186,
      a plasmid bearing the minimal 186-bp origin of the monkey origin of DNA
      replication ors8, by approximately 3.5-fold. The data suggest that specific
      dimeric combinations of the 14-3-3 isoforms have CBP activity and that
      upregulation of this activity leads to an increase in DNA replication.

PMID- 12795618
TI  - Characterization of DNA strand transfer promoted by Mycobacterium smegmatis RecA
      reveals functional diversity with Mycobacterium tuberculosis RecA.
AB  - The RecA-like proteins constitute a group of DNA strand transfer proteins
      ubiquitous in eubacteria, eukarya, and archaea. However, the functional
      relationship among RecA proteins is poorly understood. For instance,
      Mycobacterium tuberculosis RecA is synthesized as a large precursor, which
      undergoes an unusual protein-splicing reaction to generate an active form.
      Whereas the precursor was inactive, the active form promoted DNA strand transfer
      less efficiently compared to EcRecA. Furthermore, gene disruption studies have
      indicated that the frequencies of allele exchange are relatively lower in
      Mycobacterium tuberculosis compared to Mycobacterium smegmatis. The mechanistic
      basis and the factors that contribute to differences in allele exchange remain to
      be understood. Here, we show that the extent of DNA strand transfer promoted by
      the M. smegmatis RecA in vitro differs significantly from that of M. tuberculosis
      RecA. Importantly, M. smegmatis RecA by itself was unable to promote strand
      transfer, but cognate or noncognate SSBs rendered it efficient even when added
      prior to RecA. In the presence of SSB, MsRecA or MtRecA catalyzed strand transfer
      between ssDNA and varying lengths of linear duplex DNA with distinctly different
      pH profiles. The factors that were able to suppress the formation of DNA networks
      greatly stimulated strand transfer reactions promoted by MsRecA or MtRecA.
      Although the rate and pH profiles of dATP hydrolysis catalyzed by MtRecA and
      MsRecA were similar, only MsRecA was able to couple dATP hydrolysis to DNA strand
      transfer. Together, these results provide insights into the functional diversity
      in DNA strand transfer promoted by RecA proteins of pathogenic and nonpathogenic
      species of mycobacteria.

PMID- 12795619
TI  - Identification of the motifs and amino acids in aggrecan G1 and G2 domains
      involved in product secretion.
AB  - Members of the large aggregating chondroitin sulfate proteoglycans are
      characterized by an N-terminal fragment known as G1 domain, which is composed of
      an immunoglobulin (IgG)-like motif and two tandem repeats (TR). Previous studies
      have indicated that the expressed product of aggrecan G1 domain was not secreted.
      Here we demonstrated that the inability of G1 secretion was associated with the
      tandem repeats but not the IgG-like motif, and specifically with TR1 of aggrecan.
      We also demonstrated that the G2 domain, a domain unique to aggrecan, had a
      similar effect on product secretion. The sequence of TR1 of G1 is highly
      conserved across species, which suggested similar functions played by these
      motifs. In a yeast two-hybrid assay, TR1 interacted with the calcium homeostasis
      endoplasmic reticulum protein. Deletion/mutation experiments indicated that the N
      terminal fragment of TR1, in particular, the amino acids H(2)R(4) of this motif
      were key to its effect on product secretion. However, the N-terminal 55 amino
      acids were required to exert this function. Taken together, our study suggests a
      possible molecular mechanism for the function of the tandem repeats in product
      processing.

PMID- 12795620
TI  - Function of the MexB efflux-transporter divided into two halves.
AB  - The MexA-MexB-OprM efflux pump exports structurally and functionally diverse
      xenobiotics and confers multi-drug resistance on Pseudomonas aeruginosa cells.
      The MexB transporter traverses the inner membrane twelve times, bears two large
      periplasmic domains and has two homologous tandem repeats. To test whether two
      homologous halves of MexB function independently or interdependently, the protein
      was divided medially into two halves, each consisting of six amino- and carboxyl
      proximal transmembrane segments. When two halves of MexB were coexpressed from
      independent open reading frames, the cells lacking chromosomal mexB exhibited
      restored antibiotic resistance at a level close to that in the cells producing a
      full-length MexB. In contrast, MexB protein containing either an amino- or
      carboxyl-half fragment failed to transport antibiotics. To test whether the amino
      and carboxyl-proximal halves were present in a complex, we purified the
      histidine-tagged carboxyl-proximal half molecule using nickel-chelate
      chromatography from the cells that coexpressed two halves. The results showed
      that the nonhistidine-tagged amino-proximal half was co-purified with the
      carboxyl-proximal half, thereby indicating that the amino-proximal half fragment
      was tightly associated with the carboxyl-proximal half molecule. These findings
      suggest that the presence of both amino- and carboxyl-halves of MexB in a complex
      is essential for transport activity.

PMID- 12795621
TI  - Thermodynamics of fusion peptide-membrane interactions.
AB  - The fusion peptides of viral membrane fusion proteins play a key role in the
      mechanism of viral spike glycoprotein mediated membrane fusion. These peptides
      insert into the lipid bilayers of cellular target membranes where they adopt
      mostly helical secondary structures. To better understand how membranes may be
      converted to high-energy intermediates during fusion, it is of interest to know
      how much energy, enthalpy and entropy, is provided by the insertion of fusion
      peptides into lipid bilayers. Here, we describe a detailed thermodynamic analysis
      of the binding of analogues of the influenza hemagglutinin fusion peptide of
      different lengths and amino acid compositions. In small unilamellar vesicles, the
      interaction of these peptides with lipid bilayers is driven by enthalpy (-16.5
      kcal/mol) and opposed by entropy (-30 cal mol(-1) K(-1)). Most of the driving
      force (deltaG = -7.6 kcal/mol) comes from the enthalpy of peptide insertion deep
      into the lipid bilayer. Enthalpic gains and entropic losses of peptide folding in
      the lipid bilayer cancel to a large extent and account for only about 40% of the
      total binding free energy. The major folding event occurs in the N-terminal
      segment of the fusion peptide. The C-terminal segment mainly serves to drive the
      N-terminus deep into the membrane. The fusion-defective mutations G1S, which
      causes hemifusion, and particularly G1V, which blocks fusion, have major
      structural and thermodynamic consequences on the insertion of fusion peptides
      into lipid bilayers. The magnitudes of the enthalpies and entropies of binding of
      these mutant peptides are reduced, their helix contents are reduced, but their
      energies of self-association at the membrane surface are increased compared to
      the wild-type fusion peptide.

PMID- 12795622
TI  - Influence of carotenoid molecules on the structure of the bacteriochlorophyll
      binding site in peripheral light-harvesting proteins from Rhodobacter
      sphaeroides.
AB  - In the LH2 proteins from Rhodobacter (Rb.) sphaeroides, the hydrogen bonds
      between the bacteriochlorophyll (Bchl) molecules and their proteic binding sites
      exhibit a strong variance with respect to carotenoid content and type. In the
      absence of the carotenoid molecule, such as in the LH2 from Rb. sphaeroides
      R26.1, the void in the protein structure induces a significant reorganization of
      the binding site of both Bchl molecules responsible for the 850 nm absorption,
      which is not observed when the 800 nm absorbing Bchl is selectively removed from
      these complexes. FT Raman spectra of LH2 complexes from Rb. sphaeroides show that
      the strength of the hydrogen bond between the 850 nm absorbing Bchl bound to the
      alpha polypeptide and the tyrosine alpha(45) depends precisely on the chemical
      nature of the bound carotenoid. These results suggest that the variable extremity
      of the carotenoid is embedded in these LH2 complexes, lying close to the
      interacting Bchl molecules. In the LH2 from Rhodopseudomonas acidophila, the
      equivalent part of the rhodopin glucoside, which bears the glucose group, lies
      close to the amino terminal of the antenna polypeptide. This contrast suggests
      that the structure of the carotenoid binding site in LH2 complexes strongly
      depends on the bacterial species and/or on the chemical nature of the bound
      carotenoid.

PMID- 12795623
TI  - Sleep apnoea in the older adult : pathophysiology, epidemiology, consequences and
      management.
AB  - Sleep apnoea is a breathing disorder in sleep usually caused by repetitive upper
      airway obstruction. Its primary symptoms include snoring, daytime sleepiness and
      decreased cognitive functioning. Risk factors for the condition include obesity,
      anatomical abnormalities, aging, and family history. It has been associated with
      hypertension, cardiovascular and pulmonary diseases and increased mortality. The
      prevalence of sleep apnoea increases with age, although the severity of the
      disorder, as well as the morbidity and mortality associated with it, may actually
      decrease in the elderly. A decline in cognitive functioning in older adults with
      sleep apnoea may resemble dementia. Medical management of sleep apnoea rarely
      relies on drug treatment, as the few drugs (antidepressants and respiratory
      stimulants) tested for treatment have been found to be ineffective, or cause
      tolerance or serious adverse effects and complications. The treatment of choice
      for sleep apnoea is continuous positive airway pressure, a device which generates
      positive air pressure through a nose mask, creating a splint which keeps the
      airway unobstructed throughout the night. Weight loss significantly decreases or
      eliminates apnoeas. Oral appliances are used to enlarge the airway at night by
      moving the tongue and mandible forward. Positional therapy involves avoiding the
      supine position during sleep in patients who mostly have apnoeas while lying on
      their back. Surgical management may also be considered, although with great
      caution in the elderly, because of their increased risk of complications related
      to surgery. Surgical procedures include nasal reconstruction, somnoplasty, laser
      assisted uvuloplasty, uvulopalatopharyngoplasty, genioglossus advancement and
      hyoid myotomy, and maxillomandibular advancement for severe cases when other
      treatments have failed. As a last option, tracheostomy may be performed.

PMID- 12795624
TI  - The role of antivirals in the management of neuropathic pain in the older patient
      with herpes zoster.
AB  - Herpes zoster has been known since ancient times. It is a ubiquitous disease,
      occurring sporadically without any seasonal preference and is caused by the
      varicella-zoster virus. It may be defined as an endogenous relapse of the primary
      infection varicella. Herpes zoster is characterised by typical efflorescences in
      the innervation region of a cranial or spinal nerve and starts and ends with pain
      of varying intensity. Currently, several antiviral drugs are approved and many
      studies have shown that antiviral therapy, started early in the course of
      disease, can significantly reduce the risk and the duration of postherpetic
      neuralgia in elderly patients. The effects of all antivirals discussed in this
      article, given either orally or intravenously, are comparable with regards to the
      resolution of virus replication, prevention of dissemination of skin lesions and
      reduction of acute herpes zoster pain. Valaciclovir (valacyclovir), famciclovir
      and brivudine (brivudin) are comparably effective in the reduction of the
      incidence and/or prevention of zoster-associated pain and postherpetic neuralgia.
      Brivudine 125mg once daily is as effective as famciclovir 250mg three times daily
      in reducing the prevalence and the duration of zoster-associated pain and
      postherpetic neuralgia, especially if therapy is combined with a structured-pain
      therapy. The intensity of the therapy for pain should depend on the intensity of
      the pain that it is treating. Famciclovir and brivudine offer an advantage over
      other antivirals because they are administered less frequently; this is
      particularly relevant for elderly patients who may already be taking a number of
      medications for other diseases. Therefore, antiviral therapy in combination with
      adequate pain management should be given to all elderly patients as soon as
      herpes zoster is diagnosed.

PMID- 12795625
TI  - The role of opioid analgesics in rheumatoid disease in the elderly population.
AB  - Adequate pain therapy is an important aspect in the treatment of the elderly
      patient with rheumatoid disease. Problems with traditional NSAIDs include
      potentially serious gastrointestinal, cardiovascular and renal adverse effects,
      especially in the elderly. In addition, the selective cyclo-oxygenase-2
      inhibitors have been associated with renal and cardiovascular adverse effects
      which may limit their use in the elderly with renal or cardiovascular disease.
      Opioids provide a treatment option for the management of pain in elderly patients
      with rheumatoid disease in whom pain control under standard management is poor;
      however, various therapeutic difficulties are encountered in the heterogeneous
      elderly population (increased risk of adverse effects, multimorbidity, and
      polypharmacy). Lower initial opioid dosage, prolonged dosage intervals and slower
      dosage titrations are advisable because of altered pharmacokinetics and
      pharmacodynamics. Kidney function should be tightly monitored and a timely use of
      laxatives is to be encouraged. Randomised clinical studies of opioids in
      musculoskeletal pain (e.g. osteoarthritis) have increasingly extended the
      scientific basis for their use. However, no randomised controlled clinical trials
      have examined the efficacy and the benefit/risk ratio of opioids in rheumatoid
      arthritis. Opioids also demonstrate an analgesic effect following local
      peripheral application. This opens the way to new therapeutic options in the
      future through the development of systemic peripherally selective opioids without
      CNS adverse effects.

PMID- 12795629
TI  - Long-term care planning for baby boomers: addressing an uncertain future.
AB  - The number and proportion of older Americans are rising rapidly and are expected
      to increase into the middle of the 21st century as Baby Boomers reach age 65.
      Medicare has been the traditional health care insurance for the elderly. Medicare
      was enacted in a health care climate of acute care and hospitalization. Chronic
      disease is the major health care cost of the 21st century with the need for long
      term care growing rapidly. Medicare was never designed to pay for long-term care
      and custodial services. The limited scope of Medicare coverage is a problem now
      and will be a greater problem in the future. Long-term care is a personal
      responsibility and requires planning ahead. Nurses offer strategic solutions to
      meeting present and future needs by serving as educators, advocates, coordinators
      of resources, and activists working on many levels to influence care for the
      elderly now and in the future. This article focuses on the origins of traditional
      health care insurance, current and projected costs of long-term care, the current
      role of the government and private sector in financing long-term care, and
      nursing initiatives for the individual and community.

PMID- 12795628
TI  - Issues affecting the health of older citizens: meeting the challenge.
AB  - The health of older Americans will become a critical national policy issue during
      this century. As the population of older adults increases dramatically, there are
      few signs that adequate resources are available to meet the challenge of
      providing health care and good quality of life for older adults and their
      families. A fundamental change in the values emphasized in the American culture,
      and in other cultures, will be required to change the present health care system
      from one which focuses on diagnosis and treatment of disease to a system that
      attends to the major issues that affect quality of life of older adults and their
      families. This article discusses four critical areas influencing the quality of
      life of older Americans: providing resources to individuals to help manage
      chronic medical conditions, assuring a sufficient number of primary health care
      providers educated in geriatrics and gerontology, removing financial barriers to
      accessing health care and medications, and changing the American cultural value
      system that emphasizes disease treatment over providing emotional, educational,
      and support resources. To make these profound changes in the formal health care
      system, health care providers, health care organizations, and policy makers must
      commit to embracing the importance of quality of life as an integral component of
      health care for older citizens.

PMID- 12795630
TI  - Care provision for older adults: who will provide?
AB  - The aging of the baby boomers comes at a time of a growing nursing workforce
      shortage: registered nurses, nurse aides, and nursing faculty. Older adults have
      multiple physical, social, and psychological conditions, making the assessment,
      planning, and delivery of health care more complex than that of younger adults.
      Not surprisingly, this age group also utilizes the majority of health services in
      the country. Thus, most nurses will provide care to older adults in a variety of
      settings. However, the majority of nurses have little to no background in
      geriatric nursing. These multiple forces: aging population with complex needs,
      nursing work force shortage, and lack of geriatric knowledge, along with fewer
      resources, will have a grave impact on health care in this country in the near
      future. This article reviews issues related to an aging population, the projected
      nursing workforce shortage, and the lack of geriatric nursing education; it
      concludes with suggestions for future health care delivery to the geriatric
      population in the US

PMID- 12795626
TI  - Benefits of optimising drug treatment in home-dwelling elderly patients with
      coronary artery disease.
AB  - Coronary artery disease (CAD) is prevalent in the elderly and often leads to
      disability. Consequently, strategies for optimising the prevention and treatment
      of CAD in the elderly are important from both the individual and societal
      perspectives. Although it is common knowledge that the elderly are heavy
      consumers of drugs, there is evidence to show that there is under-prescribing of
      evidence-based medical therapies in the home-dwelling elderly coronary patient
      and there may be overuse of some non-evidence-based (antioxidants) and purely
      symptomatic treatments. In particular, aspirin (acetylsalicylic acid), beta
      adrenoceptor antagonists, ACE inhibitors and HMG-CoA reductase inhibitors are
      under-utilised. Although the evidence base is largely drawn from trials including
      patients younger than 75 years, it is reasonable to assume that the data applies
      to patients aged over 75 years and that better use of evidence-based medicines
      would provide benefits to the home-dwelling aged patient. Evidence from the few
      multifactorial studies available suggest possible benefits including reduction of
      cardiovascular events, less disability and better quality of life in old age. At
      the societal level, this would be reflected in fewer hospitalisations and
      institutionalisations, which means decreased cost of elderly care.

PMID- 12795631
TI  - Now you see it, now you don't: the ephemeral nature of digital information.

PMID- 12795627
TI  - Latanoprost : an update of its use in glaucoma and ocular hypertension.
AB  - Latanoprost (Xalatan) is an ester analogue of prostaglandin F2alpha that reduces
      intraocular pressure (IOP) by increasing uveoscleral outflow. The IOP-lowering
      efficacy of latanoprost 0.005% lasts for up to 24 hours after a single topical
      dose, which allows for a once-daily dosage regimen. In patients with ocular
      hypertension or open-angle glaucoma, a single drop of latanoprost 0.005% solution
      (about 1.5 microg) administered topically once daily reduced diurnal IOP by 22 to
      39% over 1 to 12 months' treatment in well-controlled trials; efficacy was
      maintained during treatment periods of up to 2 years. At this dosage, latanoprost
      was significantly more effective than timolol 0.5% twice daily in 3 of 4 large,
      double-blind, randomised studies, was generally as effective as bimatoprost or
      travoprost, and was significantly more effective than dorzolamide, brimonidine or
      unoprostone. Furthermore, in patients whose IOP was poorly controlled with
      timolol, switching to latanoprost monotherapy was at least as effective at
      lowering IOP as adding dorzolamide or pilocarpine to the regimen. Latanoprost has
      also shown significant additive effects when used in combination with one or more
      other glaucoma medications. The fixed combination of latanoprost plus timolol was
      significantly more effective than either of its individual components in two
      double-blind randomised studies and more effective than the fixed combination of
      dorzolamide and timolol in a 3-month, evaluator-masked study. Data in patients
      with angle-closure glaucoma are limited, but in patients with elevated IOP after
      undergoing iridotomy, latanoprost 0.005% once daily was significantly more
      effective than timolol 0.5% twice daily at reducing IOP over 12 weeks of
      treatment in a large double-blind, randomised study. Latanoprost is generally
      well tolerated and, unlike timolol, induces minimal systemic adverse events. In
      well-controlled, 6-month trials, the most commonly occurring drug-related ocular
      events in latanoprost recipients were mild to moderate conjunctival hyperaemia (3
      to 15%) and iris colour change (2 to 9%); these seldom required patient
      withdrawal although the latter may be permanent. Latanoprost 0.005% as a single
      daily drop has shown good IOP-lowering efficacy in patients with open-angle
      glaucoma or ocular hypertension and does not produce the cardiopulmonary adverse
      effects associated with beta-blockers. Thus, latanoprost is a valuable addition
      to the first-line treatment options for patients with open-angle glaucoma or
      ocular hypertension. In addition, adjunctive treatment with latanoprost in
      patients who are refractory to beta-blocker therapy is a viable, second-line
      treatment option. Although preliminary findings are promising, wider clinical
      experience is required to define the place of latanoprost in the treatment of
      angle-closure glaucoma.

PMID- 12795632
TI  - Smoking cessation interventions for hospitalized patients with cardio-pulmonary
      disorders.
AB  - This article reviews the evidence for effective smoking cessation interventions
      in hospitalized cardiac and pulmonary patients. Research evidence from 1992
      through June 2002 was located through searches of CINAHL (169 manuscripts),
      Medline (227 manuscripts), PsycINFO (123 manuscripts), the Cochrane Library, and
      AHCPR Clinical Practice Guidelines. Seventy-one studies were critiqued for this
      review. The results of the searches indicated that cigarette smoking and nicotine
      dependence exponentially increase risk factors for cardiac and pulmonary
      diseases. Stages of smoking behavior change and readiness to quit were identified
      as major components in the process of smoking cessation. Factors predicting
      success and change activities include: higher education, level of craving or
      nicotine dependence, and social support by work or family/friends. Risk factors
      for relapse include: work environment/stress and other smokers in the home or
      workplace. Hospitalized patients were shown to be in a "window of opportunity"
      for assisting the behavior change process of smoking cessation due to increased
      health motivation.

PMID- 12795634
TI  - Challenges and solutions for care of frail older adults.
AB  - Frail older adults are at risk for negative outcomes and are the most significant
      consumers of health resources across both acute and community settings. Both
      formal systems and families are involved in this care of frail elders. This
      article reviews health care issues for frail older adults and addresses the
      impact of frailty on the future health care system. It also presents challenges
      for future care, creative solutions that are currently being tested and explored,
      and suggestions for future nursing priorities. Challenges in the care of frail
      elders include: the organization and sustainability of the continuum of services,
      resource allocation, and cultural competence in service delivery. Creative
      solutions include intensive case management programs, targeting at risk older
      adults, partnerships with families, enhanced use of telemedicine and assistive
      technology, and promoting healthy aging. Nurses have the potential to improve
      elder health across settings through clinical practice, education, leadership,
      and research.

PMID- 12795635
TI  - Behavioral determinants of healthy aging: good news for the baby boomer
      generation.
AB  - The first of the Baby Boomer generation will officially enter the beginning of
      old age in 2011 by turning 65. Recent research findings suggest that if the
      members of this cohort group engage in certain healthy behaviors and thought
      patterns in their middle years, they will experience a vital, satisfying life in
      their 70s and beyond. This article reviews the existing literature, including the
      results of longitudinal studies showing variables that predicted successful
      aging. Focusing on a lifespan psychology perspective of aging, the authors
      provide behavioral recommendations for middle age individuals that are likely to
      prevent disease-related disability, cognitive impairment, and late life
      depression. These include regular physical exercise, engaging in cognitively
      stimulating activities, maintaining an optimistic mental outlook, and finding
      meaning in life. The good news for the Baby Boomers is that there is increasing
      evidence that their behavior at age 50 will impact how they feel at age 80.

PMID- 12795636
TI  - A novel serine protease predominately expressed in macrophages.
AB  - We have identified a novel serine protease designated EOS by sequence identity
      searches. The deduced protein contains 284 amino acids with an active form
      containing 248 amino acids starting from an Ile-Val-Gly-Gly motif. The active
      form comprises a catalytic triad of conserved amino acids: His77, Asp126 and
      Ser231. It shares 44% identity with beta-tryptase and belongs to the S1 trypsin
      like serine-protease family. Interestingly, this gene also maps to human
      chromosome 16p13.3. The purified protease showed amidolytic activity, cleaving
      its substrates before arginine residues. Tissue distribution by
      immunohistochemistry analysis demonstrated that EOS is highly expressed in spleen
      and moderately expressed in intestine, colon, lung and brain. We confirmed this
      expression pattern at the mRNA level by performing in situ hybridization. The
      results from both immunohistochemistry and in situ hybridization indicate that
      EOS is associated with macrophages. We corroborated this observation by double
      immunofluorescence using the anti-EOS antibody and an anti-CD68 antibody, a
      macrophage specific marker. Furthermore, we have detected a dramatic increase in
      immune staining of EOS in cultured U937 cells treated with PMA, which represent
      activated macrophages. This up-regulation is also reflected by elevated EOS mRNA
      in the PMA-treated U937 cells detected by Northern blotting. Since macrophages
      have important roles in various pathological conditions, such as wound healing,
      atherosclerosis and numerous inflammatory diseases, the localization of this
      novel serine protease to active macrophages may help to further the elucidation
      of the roles of this gene product in modulating these disorders.

PMID- 12795637
TI  - A study of host defence peptide beta-defensin 3 in primates.
AB  - We have investigated the molecular evolution of the gene coding for beta-defensin
      3 (DEFB103) in 17 primate species including humans. Unlike the DEFB4 genes
      (coding for beta-defensin 2) [Boniotto, Tossi, Del Pero, Sgubin, Antcheva, Santon
      and Masters (2003) Genes Immun. 4, 251-257], DEFB103 shows a marked degree of
      conservation in humans, Great Apes and New and Old World monkeys. Only the
      Hylobates concolor defensin hcBD3 showed an amino acid variation Arg17-->Trp17
      that could have a functional implication, as it disrupts an intramolecular salt
      bridge with Glu27, which locally decreases the charge and may favour dimerization
      in the human congener hBD3. This is thought to involve the formation of an
      intermolecular salt bridge between Glu28 and Lys32 on another monomer [Schibli,
      Hunter, Aseyev, Starner, Wiencek, McCray, Tack and Vogel (2002) J. Biol. Chem.
      277, 8279-8289]. To test the role of dimerization in mediating biological
      activity, we synthesized hBD3, hcBD3 and an artificial peptide in which the Lys26
      Glu27-Glu28 stretch was replaced by the equivalent Phe-Thr-Lys stretch from human
      beta-defensin 1 and we characterized their structure and anti-microbial activity.
      Although the structuring and dimerization of these peptides were found to differ
      significantly, this did not appear to affect markedly the anti-microbial potency,
      the broad spectrum of activity or the insensitivity of the anti-microbial action
      to the salinity of the medium.

PMID- 12795638
TI  - Investigation of the pore-forming mechanism of a cytolytic delta-endotoxin from
      Bacillus thuringiensis.
AB  - Cyt2Aa1 is a cytolytic protein produced by Bacillus thuringiensis subsp.
      kyushuensis. Penetration of the toxin into membranes has been studied to learn
      more about membrane-insertion mechanisms and transmembrane-pore formation. The
      haemolysis assay of Cyt2Aa1 showed a steep and sigmoidal dose-response curve,
      indicating that toxin aggregation or oligomerization is required for pore
      formation. Studies of the effect of temperature on pore formation and
      fluorimetric studies of acrylodan-labelled toxin suggest that toxin inserts into
      the membrane before oligomerizing to form a pore. Low temperature neither
      inhibited membrane binding nor closed pores that have been formed, but markedly
      inhibited oligomerization of the toxin molecules. When toxin-treated red blood
      cells at 4 degrees C were transferred to a toxin-free solution at 37 degrees C,
      no significant increase in haemolysis was observed. This result suggests that
      membrane-bound toxin could not diffuse laterally and interact with other
      molecules to form a pore. From these results, we propose that Cyt2Aa1 binds and
      inserts into the membrane as a monomer. Oligomerization occurs when toxin
      molecules have bound in close proximity to each other and pores are formed from
      large oligomers.

PMID- 12795639
TI  - Prognostic significance of soluble interleukin-2 receptor levels in patients with
      dilated cardiomyopathy.
AB  - BACKGROUND: Activation of T lymphocytes is thought to mediate myocardial
      dysfunction in dilated cardiomyopathy (CMP), probably through cytotoxic
      cytokines, but its value as a prognostic factor has not been evaluated. METHODS:
      For 2 years we prospectively followed 76 patients (65 males, 11 females, age 49
      +/- 7 years) with CMP and New York Heart Association(NYHA) Class II-III heart
      failure; left ventricular (LV) function was assessed echocardiographically.
      Thirty-three patients (28 males, five females, age 52 +/- 6 years) with ischaemic
      heart disease (IHD) and similar NYHA and LV function characteristics were used as
      controls. Serum sIL-2R levels, peripheral blood lymphocyte proliferation (basal,
      + concanavalin A) and HLA-DQB1 genotyping was carried out in all patients.
      RESULTS: The CMP patients had increased sIL-2R levels (1259 +/- 130 pg mL-1)
      compared with the IHD patients (703 +/- 80 pg mL-1, P < 0.01, only 3 > 800 pg mL
      1). In the CMP patients, there was a significant (r = +0.45, P= 0.04) correlation
      between sIL-2R and the LV end-diastolic diameter but not with the LV ejection
      fraction or NYHA Class. During the 24-month follow up, 17 of the CMP patients had
      an adverse clinical course (death, need for cardiac transplantation, or worsening
      heart failure). Of these, 14 (75%) had elevated (>or= 800 pg mL-1) sIL-2R levels
      (Group I) compared with only five (6%) with a stable clinical course (Group II).
      Neither [3H] thymidine incorporation into the peripheral blood lymphocytes nor
      the excess of HLA-DQB1-30 histidine homozygotes in the Group I patients (38% vs.
      17%, P < 0.05) could predict the clinical outcome. CONCLUSION: Increased sIL-2R
      levels in CMP patients are an independent predictor of a more aggressive clinical
      course.

PMID- 12795640
TI  - Urinary excretion of complement C3d in patients with renal diseases.
AB  - INTRODUCTION: Complement-mediated tubular injury may play an important role in
      the progression of renal diseases. C3d is a presumed marker of complement
      activation. Its precursor C3dg has been detected in the urine of patients with
      membranous nephropathy. However, little is known of the renal handling of C3d or
      its excretion in other renal diseases. METHODS: We measured the urinary excretion
      of albumin, IgG, beta2-microglobulin (beta2m), and of complement C3d in patients
      with tubulo-interstitial nephritis (TIN; n= 8), in patients with membranous
      nephropathy (n = 35) and in patients with nonmembranous glomerular diseases (23
      nonproliferative and 21 proliferative). Fractional excretions (FE) were
      calculated using creatinine clearance as marker of GFR. RESULTS: C3d was not
      measurable in the urine of the healthy controls, but was detectable in seven out
      of eight of the TIN patients (median excretion 0.11 mU min-1, range 0.006-2.4 mU
      min-1). In these patients the urinary excretion of beta2m was clearly elevated
      (median 26.6 micro g min-1, range 1.0-103 micro g min-1). The FE of C3d
      correlated with the FE of beta2microglobulin (r = 0.83, P = 0.01), and their
      ratio amounted to 0.03 (range 0.003-0.06), a value in agreement with the expected
      sieving coefficient. Urine C3d was detectable in all but three of the patients
      with glomerular diseases (median excretion 0.36 mU min-1, range 0.004-7.9 mU min
      1); C3d-excretion did not differ between the three subgroups of patients with
      glomerular diseases. FEC3d correlated with FEIgG (r = 0.88, P < 0.01). The ratio
      FEC3d/FEbeta2m was 0.78 (range 0.04-9.99). Selected patients with membranous
      nephropathy were re-analyzed after (partial) remission of proteinuria. Reduction
      of proteinuria resulted in a decrease of C3d excretion. CONCLUSION: Urinary
      excretion of C3d is elevated in patients with TIN, most likely as a mere
      consequence of decreased tubular reabsorption. In patients with glomerular
      diseases urinary excretion of C3d is increased and related to proteinuria,
      independent of the underlying glomerular disease. In these patients there is
      evidence of increased local formation of C3d.

PMID- 12795641
TI  - Low HDL cholesterol concentration is associated with increased intima-media
      thickness independent of arterial stiffness in healthy subjects from families
      with low HDL cholesterol.
AB  - BACKGROUND: Low high-density lipoprotein cholesterol (HDL-C) is associated with
      increased risk for developing coronary artery disease. Cardiovascular disease is
      characterized by increased intima-media thickness (IMT) and arterial stiffness,
      but the effect of low HDL on these measurements has not been reported. MATERIALS
      AND METHODS: We studied 18 apparently healthy subjects from families with low HDL
      C and 18 control subjects, which were pair-matched to maximize statistical power.
      Intima-media thickness was assessed using ultrasound examination of the carotid
      arteries. Arterial stiffness was measured using applanation tonometry on the
      radial artery and pulse-wave analysis to obtain central aortic pulse-pressure
      waveform, from which the augmentation index, a measure of global large artery
      stiffness, was calculated. RESULTS: Low HDL subjects (age 41 +/- 3 years, BMI
      26.6 +/- 1.0 kg m(-2) had significantly lower HDL-C than the control subjects
      (age 41 +/- 3 years, BMI 26.5 +/- 1.0 kg m-2; 1.00 +/- 0.05 vs. 1.49 +/- 0.09
      mmol L-1, low HDL vs. control subjects, P < 0.0001). Subjects with low HDL-C had
      significantly thicker mean IMTs than the control subjects (0.77 +/- 0.03 vs. 0.70
      +/- 0.02 mm, low HDL vs. control subjects, P < 0.01). The maximal (0.99 +/- 0.04
      vs. 0.89 +/- 0.03 mm, P < 0.01), far wall (0.76 +/- 0.04 vs. 0.69 +/- 0.02 mm, P
      < 0.05) and carotid bulb (1.11 +/- 0.06 vs. 0.97 +/- 0.04 mm) IMTs were also
      significantly increased, whereas the mean common carotid and the internal artery
      IMT were not. The age-related increase in mean IMT was more pronounced in the low
      HDL subjects than the control subjects (P < 0.01 for difference between
      elevations of age vs. IMT slopes). There were no differences in central pressure
      augmentation, the augmentation index, peripheral or central blood pressures
      between the groups. CONCLUSIONS: A low HDL-C concentration is associated with
      thickening of carotid IMT independent of other risk factors in healthy affected
      members of low HDL families.

PMID- 12795642
TI  - Fatty acids modulate the effect of darglitazone on macrophage CD36 expression.
AB  - BACKGROUND: Scavenger receptor-mediated uptake of cholesterol by macrophages in
      the arterial wall is believed to be proatherogenic. Thiazolidinediones are
      peroxisome proliferator-activated receptor gamma (PPARgamma)-agonists, which are
      used in the treatment of type II diabetes. They reduce atherogenesis in LDL
      receptor deficient and ApoE knockout mice, but up-regulate CD36, which may
      contribute to foam cell formation. The dyslipidaemia in type II diabetes is
      characterized by high levels of nonesterified fatty acids. Therefore we tested
      the effect of fatty acids and how fatty acids and the thiazolidinedione
      darglitazone interact in their effect on CD36 expression in human monocytes and
      macrophages. MATERIALS AND METHODS: Flow cytometry and reverse transcription
      polymerase chain reaction were used to study CD36 expression. Cellular lipids
      were analyzed with high performance liquid chromatography. RESULTS: Darglitazone
      increased CD36 mRNA and protein expression in human macrophage cells. In the
      presence of 5% human serum, darglitazone increased the accumulation of
      triglycerides, but did not affect cholesterol ester levels. In the presence of
      albumin-bound oleic or linoleic acid, darglitazone did not increase CD36 mRNA,
      cell-surface CD36 protein or triglyceride content. Fatty acids per se increased
      CD36 mRNA and protein. DISCUSSION: The increase in CD36 in macrophages suggests a
      role for fatty acids in the regulation of foam cell formation. The results also
      suggest that the potentially proatherogenic CD36 up-regulating effect of
      thiazolidinediones in macrophages might not be present when the cells have access
      to physiological levels of albumin-bound fatty acids.

PMID- 12795643
TI  - Influence of glucose control, lipoproteins, and haemostasis function on brachial
      endothelial reactivity and carotid intima-media area, stiffness and diameter in
      Type 1 diabetes mellitus patients.
AB  - BACKGROUND: The objectives of this study were to determine the influence of
      glucose control on lipoprotein and haemostasis variables in Type 1 diabetes
      mellitus patients and to evaluate the global impact of these metabolic risk
      factors on brachial artery reactivity and carotid artery atherosclerosis,
      stiffness and diameter. DESIGN: Follow up of Type 1 diabetes patients randomized
      to insulin-intensive conventional treatment (ICT, n = 29) or insulin-standard
      treatment (ST, n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more
      than 14 years ago. RESULTS: The intensive conventional treatment patients had
      lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7.01
      (SD 0.51) vs. 8.31 (0.97), while concentrations of the lipoprotein and
      haemostasis variables analyzed were virtually similar. The carotid artery intima
      media area was associated with high HbA1c, high serum (S)-cholesterol levels, and
      low high-density lipoprotein (HDL)-cholesterol levels. Carotid artery stiffness
      was associated with high systolic blood pressure, high HbA1c, high fibrinogen,
      and high HDL-cholesterol. Brachial artery endothelial reactivity was higher for
      women and those with low S-cholesterol. CONCLUSION: In patients with Type 1
      diabetes, glucose control appeared to have no effect on either lipoproteins or
      haemostasis variable concentrations. Poor glucose control, and high levels of S
      cholesterol, systolic blood pressure and plasma fibrinogen were associated with
      development of atherosclerosis, thus emphasising the importance of global risk
      factor control in patients with Type 1 diabetes mellitus.

PMID- 12795644
TI  - Exercise induces excessive normetanephrine responses in hypertensive diabetic
      patients.
AB  - BACKGROUND: Exaggerated sympathoadrenal function has been accused of contributing
      to hypertension in type-2 diabetes. Recently, plasma unconjugated (free)
      metanephrines were reported to be stable markers of catecholamine hypersecretion.
      Thus, we aimed to examine whether unconjugated metanephrines are reliable markers
      of stress response induced by standardized cycling exercise and to identify
      differences in such stress responses between hypertensive and/or diabetic
      patients. DESIGN: Type-2 diabetic patients with (DM/H; n= 8, 50 +/- 7 years,
      HbA1c: 7.7 +/- 0.6%) or without hypertension (DM/N; n = 6, 48 +/- 10 years, 7.5
      +/- 1.8%) and nondiabetic hypertensive patients (H; n = 8, 56 +/- 4 years) were
      studied during incremental cycling exercise (15 min) to 75% of individual
      VO(2)max and during recovery (60 min). Plasma catecholamines and unconjugated
      metanephrines were measured by high-performance liquid chromatography with
      electrochemical detection. Hormone responses were quantified from the areas under
      the concentration-time curves and compared with those of age-, sex- and BMI
      matched healthy volunteers (CON, n= 22). RESULTS: Blood pressure responses of
      DM/H and H, but not DM/N, were greater than those of CON (P < 0.01), whereas
      heart rates increased similarly in all groups. Unconjugated normetanephrine
      responses were only increased (P = 0.04) in DM/H (2156 vs. 1133 pg mL(-1) min(-1)
      but not in DM/N (1528 vs. 1300 pg mL(-1) min(-1) and H (1960 vs. 1425 pg mL(-1)
      min(-1) when compared with respective CON. Unconjugated metanephrines did not
      change from baseline, whereas catecholamine responses were comparable in all
      groups. CONCLUSIONS: The excessive response of plasma unconjugated
      normetanephrine to cycling may serve as a marker of exaggerated sympathoadrenal
      function in hypertensive type-2 diabetic patients.

PMID- 12795645
TI  - Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.
AB  - BACKGROUND: Nesidioblastosis in adults has been reintroduced into the
      differential diagnosis of organic hyperinsulinism by the description of
      'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. MATERIALS AND
      METHODS: Pathologic specimens of all adult patients (n = 66) operated on for
      organic hyperinsulinism were re-examined. Five patients fulfilled the
      histomorphological criteria of nesidioblastosis. Retrospective review of clinical
      presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre
      and intraoperative localization studies and surgical therapy was performed.
      RESULTS: In contrast to NIPHS, fasting tests became positive after 8-14 h.
      Tolbutamide tests were positive and preoperative imaging showed negative results
      in all patients. At first operation distal pancreatic resections were performed
      in three patients, resection of the pancreatic body in one patient and biopsy of
      the pancreatic tail in one patient. Two of three patients with recurrent disease
      had to be reoperated. One patient showed a coexistence of nesidioblastosis and
      multiple small insulinomas and is part of a kindred with autosomal dominantly
      inherited 'familial islet-cell adenomatosis'. CONCLUSIONS: Surgical exploration
      is indicated only after thorough biochemical diagnosis. An aggressive strategy
      for preoperative localization including selective arterial calcium stimulation
      testing seems justified. There may be a combination of nesidioblastosis and islet
      cell tumours. A link between beta-cell hyperplasia and progression to insulinoma
      based on not yet known genetic causes can be suspected.

PMID- 12795646
TI  - Variable expression of CYP and Pgp genes in the human small intestine.
AB  - BACKGROUND: The small intestine is receiving increased attention for its
      importance in drug metabolism. However, knowledge of the intervariability and
      regulation of the enzymes involved, cytochrome p450 and P-Glycoproteins (CYP and
      Pgp), is poor when compared with the corresponding hepatic enzymes. METHODS: The
      expression of eight different CYP genes and the Pgp were determined by reverse
      transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies.
      And the variability and correlation of expression was analyzed. RESULTS:
      Extensive interindividual variability was found in the expression of most of the
      genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and
      CYP2E1 exhibited the highest interindividual variability. No strong correlation
      of expression existed between the genes. But a highly significant correlation was
      found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and
      omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4,
      respectively. CONCLUSIONS: Extensive interindividual variability is
      characteristic for the expression of drug-metabolizing CYP and Pgp genes in human
      duodenum, and external factors such as drugs may further increase the
      variability. It is possible that the large interindividual variability may lead
      to variable bioavailability of orally used drugs and hence complicate optimal
      drug therapy, especially for drugs with a small therapeutic window. Elucidation
      of factors contributing to clinically important variances warrants further
      investigation.

PMID- 12795647
TI  - Heat-shock protein 70 favours human liver recovery from ischaemia-reperfusion.
AB  - BACKGROUND: Pringle's manoeuvre controls excessive bleeding, but results in
      ischaemia-reperfusion injury during liver surgery. Activation of the heat-shock
      protein system of cell defense has been demonstrated after ischaemia-reperfusion
      injury in animal tissues. The aim of the present study was to determine whether
      the ischaemia-reperfusion accompanying hepatic surgery induces heat-shock protein
      70 (HSP70) in human liver and whether the induction of HSP70 is related to the
      recovery of liver function. METHODS: Heat-shock protein 70 and gamma-actin mRNAs
      were assayed in the liver biopsies of 10 subjects undergoing partial hepatectomy
      for localized lesions. Measurements were performed before the Pringle's manoeuvre
      and at the end of the surgery. Transaminases and fibrinogen were measured before
      and at 12, 24 and 36 h following hepatectomy. RESULTS: After an average 40 +/- 8
      min period of warm ischaemia, a significant increase of HSP70 mRNA (187 +/- 67%,
      2P < 0.05) was observed. The acute increase of HSP70 mRNA correlates with the
      decrease of transaminases (AST: rs -0.964, ALT: rs -0.891, P < 0.002) and the
      increase of fibrinogen (rs -0.7, P < 0.02) observed between 12 and 24 h following
      surgery. CONCLUSIONS: Heat-shock protein 70 is induced by ischaemia-reperfusion
      injury in human liver. Its induction seems to have beneficial effects, including
      a prompt reduction of transaminases and a rapid recovery of fibrinogen synthesis.

PMID- 12795648
TI  - Cyclooxygenase expression in splanchnic hyposensitivity to glypressin of bleeding
      portal hypertensive rats.
AB  - BACKGROUND: Prostacyclin mediates, at least partly, the splanchnic vascular
      hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study
      investigated the relative contribution of cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) in the splanchnic hyposensitivity to glypressin in rats
      with portal hypertension induced by partial portal vein ligation (PVL). METHODS:
      Fourteen days after the operation, the rats were divided into without- and with
      bleeding groups. Three series of PVL rats were used to investigate (i). the
      haemodynamic effects of glypressin (0.07 mg x kg(-1) intravenously), (ii). COX
      1/COX-2 mRNA expression over abdominal aorta and superior mesenteric artery and
      (iii). plasma levels of 6-keto-prostaglandin-F1alpha. In rats with a hypotensive
      haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was re
      infused before blood and vessel sampling or the administration of glypressin.
      RESULTS: Splanchnic hyposensitivity to glypressin was demonstrated in the
      haemorrhage-transfused PVL rats with enhanced COX-1 expression of superior
      mesenteric artery and increased plasma levels of 6-keto-prostaglandin-F1alpha.
      There were no differences in the COX-2 expression of superior mesenteric artery
      and COX-1 and COX-2 expressions of abdominal aorta between without- and with
      bleeding groups. CONCLUSION: In portal hypertensive rats with acute haemorrhage,
      COX-1 over-expression in the superior mesenteric artery plays a role in mediating
      the splanchnic hyposensitivity to glypressin.

PMID- 12795649
TI  - Enhancement of allergic skin wheal responses in patients with atopic
      eczema/dermatitis syndrome by playing video games or by a frequently ringing
      mobile phone.
AB  - BACKGROUND: Playing video games causes physical and psychological stress,
      including increased heart rate and blood pressure and aggression-related
      feelings. Use of mobile phones is very popular in Japan, and frequent ringing is
      a common and intrusive part of Japanese life. Atopic eczema/dermatitis syndrome
      is often exacerbated by stress. Stress increases serum IgE levels, skews cytokine
      pattern towards Th2 type, enhances allergen-induced skin wheal responses, and
      triggers mast cell degranulation via substance P, vasoactive intestinal peptide
      and nerve growth factor. MATERIALS AND METHODS: (1). In the video game study,
      normal subjects (n = 25), patients with allergic rhinitis (n = 25) or atopic
      eczema/dermatitis syndrome (n = 25) played a video game (STREET FIGHTER II) for 2
      h. Before and after the study, allergen-induced wheal responses, plasma levels of
      substance P, vasoactive intestinal peptide and nerve growth factor, and in vitro
      production of total IgE, antihouse dust mite IgE and cytokines were measured.
      (2). In the mobile phone study, normal subjects (n = 27), patients with allergic
      rhinitis (n = 27) or atopic eczema/dermatitis syndrome (n = 27) were exposed to
      30 incidences of ringing mobile phones during 30 min. Before and after the study,
      allergen-induced wheal responses, plasma levels of substance P, vasoactive
      intestinal peptide and nerve growth factor were measured. RESULTS: Playing video
      games had no effect on the normal subjects or the patients with allergic
      rhinitis. In contrast, playing video games significantly enhanced allergen
      induced skin wheal responses and increased plasma levels of substance P,
      vasoactive intestinal peptide and nerve growth factors in the patients with
      atopic eczema/dermatitis syndrome. Moreover, playing video games enhanced in
      vitro production of total IgE and anti-house dust mite IgE with concomitant
      increased production of IL-4, IL-10 and IL-13 and decreased production of IFN
      gamma and IL-12 in the patients with atopic eczema/dermatitis syndrome. However,
      exposure to frequently ringing mobile phones significantly enhanced allergen
      induced skin wheal responses, plasma levels of substance P, vasoactive intestinal
      peptide and nerve growth factors in the patients with atopic eczema/dermatitis
      syndrome, but not in the normal subjects or the patients with allergic rhinitis.
      CONCLUSION: Playing video games enhanced allergic responses with a concomitant
      increased release of substance P, vasoactive intestinal peptide and nerve growth
      factor, and skewing of the cytokine pattern toward Th2 type in the patients with
      atopic eczema/dermatitis syndrome. In addition, exposure to frequently ringing
      mobile phones also enhanced allergic responses with a concomitant increased
      release of substance P, vasoactive intestinal peptide and nerve growth factor
      Collectively, high technology causes stress, which in turn may aggravate symptoms
      of atopic eczema/dermatitis syndrome.

PMID- 12795650
TI  - Broad identification of bacterial type from pus by 1H MR spectroscopy.
AB  - BACKGROUND: Abscess formation is a common bacterial infection and requires an
      immediate antimicrobial approach for apposite treatment. Delay in patient
      treatment is usually a common feature, as the bacterial identification of
      clinical samples is based on the culture, which is a time-consuming exercise. The
      current study was aimed at developing an alternative technique with the potential
      for rapid bacterial group identification. MATERIALS AND METHODS: In the present
      study we performed ex vivo proton magnetic resonance spectroscopy of 40 pus
      samples collected from abscesses in different locations and the results have been
      retrospectively compared with the microorganism identified in the pus culture. In
      addition, the microbes obtained from the culture have been further subcultured
      and studied with magnetic resonance spectroscopy to identify the bacterial
      fingerprint in the pus sample seen on spectroscopy. RESULTS: On reviewing the
      spectra obtained from the various abscesses, they were found to be qualitatively
      similar for a particular bacterium. The similar spectral pattern of the pus with
      obligate aerobes/anaerobes and pure cultures of the same bacteria suggests its
      strict metabolism under in vivo and in vitro conditions, respectively.
      CONCLUSIONS: The characteristic metabolite pattern of obligate anaerobes may be
      used as a prototype for its rapid identification. This information may be of
      value for more appropriate clinical management of such cases.

PMID- 12795651
TI  - Leptin and proinflammatory cytokines in patients undergoing peritoneal dialysis.

PMID- 12795652
TI  - End-stage renal disease: a state of chronic inflammation and hyperleptinemia.

PMID- 12795654
TI  - Angiotensin converting enzyme inhibitors and modulation of skeletal muscle
      insulin resistance.

PMID- 12795655
TI  - Limitations to subcutaneous insulin administration in type 1 diabetes.

PMID- 12795656
TI  - Rapid reversal of hepatic steatosis, and reduction of muscle triglyceride, by
      rosiglitazone: MRI/S studies in Zucker fatty rats.
AB  - AIM: This study aimed to chart the time course and durability of the effects of
      rosiglitazone, a potent thiazolidinedione-based peroxisome proliferator-activated
      receptor gamma agonist, on hepatic steatosis and intramyocellular lipid in an
      animal model of obesity, the Zucker Fatty (ZF) rat. METHODS AND RESULTS:
      Rosiglitazone (3 mg/kg/day p.o.) significantly reduced both liver fat content (by
      59%; p < 0.05) and size (11.5%; p < 0.05) in male ZF rats that received between 3
      days and 1 week of treatment, and these reductions were maintained for at least
      12 weeks. Liver fat content measured by magnetic resonance spectroscopy (MRS)
      correlated closely and positively with plasma insulin levels (reduced by 89%
      within a week, r = 0.8) and with postmortem histological fat fractional volume (r
      = 0.89). Similarly, liver volume measured by magnetic resonance imaging (MRI)
      correlated closely with postmortem wet weight (r = 0.99). MRS also showed, and
      numbers of lipid vacuoles counted in transmission electron micrographs confirmed,
      that rosiglitazone significantly reduced the elevated intramyocellular lipid seen
      in ZF rat skeletal muscle by at least 40% (p < 0.05). CONCLUSIONS: Localized MRS
      and MRI showed that rosiglitazone reversed the hepatic steatosis, hepatomegaly
      and intramyocellular lipid, characteristic of the ZF rat, an animal model of
      obesity.

PMID- 12795657
TI  - A cohort study of reproductive risk factors, weight and weight change and the
      development of diabetes mellitus.
AB  - AIMS: Reproductive factors (parity, miscarriages, terminations), oral
      contraceptive use, hormone replacement therapy, body weight at first pregnancy
      and weight gain following pregnancy may be associated with a long-term risk of
      diabetes. The aim of this study is to investigate the independent risks of
      reproductive factors and body weight for diabetes in later life. METHODS: This is
      a retrospective cohort study of 1257 parous women who had a first pregnancy
      between 1951 and 1970. Reproductive history, weight and height were measured at
      the time of first pregnancy, then assessed by questionnaire in 1997 for all
      women. A clinical examination and an analysis of blood samples were undertaken
      for 992 women. The main outcome was incidence of diabetes based on medical
      history, medication and random glucose measurement. RESULTS: Sixty of the 1257
      (4.8%) women developed diabetes. Body mass index at index pregnancy and after 28
      48 years follow-up were both significantly associated with risk of diabetes, this
      increased with greater weight gain. There was a non-significant increased risk of
      diabetes associated with stillbirths and miscarriages after age and BMI
      adjustment. CONCLUSIONS: In parous women, higher BMI at index pregnancy, weight
      gain during follow-up and BMI in later life strongly predict diabetes risk.

PMID- 12795658
TI  - Glimepiride reduces mononuclear activation of the redox-sensitive transcription
      factor nuclear factor-kappa B.
AB  - AIMS: Glimepiride has the lowest ratio of insulin release to glucose decrease
      compared with other sulphonylureas. This prompted us to study in vitro and in
      vivo in a placebo-controlled study the effect of glimepiride on the redox
      sensitive transcription factor nuclear factor-kappa B (NF-kappaB). METHODS:
      Fifteen patients with type 2 diabetes on glibenclamide with a stable HbA1c over
      the last 6 months were included. After sampling for determination of baseline
      values, 10 patients were changed to an equivalent dose of glimepiride, while the
      placebo group was maintained at glibenclamide plus placebo. The glimepiride dose
      in these patients was adjusted so that no change in glucose control occurred,
      allowing for direct comparison. The others were kept on glibenclamide and
      received additional placebo. After 4 weeks of glimepiride or glibenclamide plus
      placebo, a second blood sample was taken. Mononuclear cells were isolated and
      assayed in a tissue-culture-independent electrophoretic mobility shift assay
      (EMSA)-based detection system for NF-kappaB binding activity, and by Western Blot
      for nuclear localization of NF-kappaB-p65, the cytoplasmic content of
      IkappaBalpha and the NF-kappaB-controlled haemoxygenase-1. Glimepiride dose
      dependent inhibition of carboxymethyllysin (CML) albumin or tumour necrosis
      factor alpha (TNFalpha)- and H2O2-induced activation of NF-kappaB binding were
      determined, using isolated peripheral blood mononuclear cells from healthy
      volunteers, and transcriptional activity of bovine aortic endothelial cells
      either left untreated or induced with CML albumin incubated with or without
      glimepiride. Furthermore, in-vitro studies were implemented to demonstrate
      radical quenching properties of glimepiride in the cell-free 2,2'-azo-bis(2
      aminopropane)-dihydrochloride system. RESULTS: Baseline glucose and HbA1c
      remained stable in the patients switched from glibenclamide to a corresponding
      dose of glimepiride or kept on glibenclamide plus placebo. While in the group of
      patients only taking glibenclamide plus placebo the NF-kappaB binding activity
      did not change significantly (p = 0.58), the NF-kappaB binding activity in the
      group of patients taking glimepiride was reduced from 19.3 relative NF-kappaB-p65
      equivalents to 15.5 relative NF-kappaB-p65-equivalents (p = 0.04). The nuclear
      translocation of NF-kappaB-p65 was reduced from 100% at baseline to 58% after 4
      weeks (p = 0.04); the cytoplasmic localization of NF-kappaB-p65 increased from
      100% to 129% (p = 0.03) and the cytoplasmic content of IkappaBalpha increased
      from 100% to 109% (p = 0.06). The redox-sensitive haemoxygenase-1 antigen was
      reduced from 100% to 82% (p = 0.04). To prove directly that glimepiride reduces
      NF-kappaB activation, we isolated peripheral blood mononuclear cells (PBMC) from
      healthy volunteers. In vitro, glimepiride reduced TNFalpha-(1 nmol/l) and CML
      albumin (800 nmol/l)-induced NF-kappaB activation dose dependently, being half
      maximal at 120 micromol/l. H2O2-mediated NF-kappaB activation was only partially
      reduced. In addition, glimepiride reduced NF-kappaB-dependent gene expression
      using a NF-kappaB-driven luciferase reporter system. Finally, a cell-free
      detection system showed that glimepiride has radical quenching properties.
      CONCLUSION: Glimepiride can affect the activation of the redox-sensitive
      transcription factor NF-kappaB in vitro and in vivo.

PMID- 12795660
TI  - Proceedings of the South Eastern Organ Procurement Foundation Meeting. 19-20
      September 2002, New Orleans, Louisiana, USA.

PMID- 12795659
TI  - Uncertain clinical utility of contemporary strategies for microalbuminuria
      testing.
AB  - AIMS: To determine whether conventional dipstick tests for proteinuria accurately
      identified patients with diabetic nephropathy and whether repeat testing for
      elevated albumin excretion and screening for urinary tract infection was required
      as part of the screening process for microalbuminuria. METHODS: Random urine for
      albumin/creatinine ratio (ACR) was measured in all patients over a 6-month
      period. Patients who had a positive test (>3.5 mg/mmol) were requested to provide
      two further samples for re-testing and a mid-stream urine specimen to screen for
      asymptomatic bacteriuria. The evaluation of accuracy of dipstick proteinuria was
      carried out in the samples collected over a fixed 2-week period. RESULTS:
      Dipstick vs. ACR--Of 221 samples collected, 142 were negative, 58 had 1+ and 21
      had 2+ or more for dipstick proteinuria. At a threshold of 2+, the majority (81%)
      had ACR in the overt nephropathy range (>30 mg/mmol) and none had it below 10
      mg/mmol, whereas at 1+, only 28% had ACR in the overt nephropathy range and 19%
      even had normoalbuminuria. Repeat Testing--Of the 1832 patients who had
      microalbuminuria measured, 673 had a positive test and 248 returned repeat
      samples. Eighty-one patients returned two samples, of which 16 had discordant
      results, and 161 patients gave three samples, of which only 23 were false
      positives. The majority of these 39 patients had low-grade microalbuminuria (ACR
      3.5-10 mg/mmol) in their first sample. The absolute benefit of repeat testing was
      only to 3.4% of the population who screened positive, while in a further 2.3%
      (two-sample responders) there was potential for confusion because of discordant
      results. Infection Screening--Of the 248 samples, only 31 had evidence of urinary
      infection. CONCLUSION: Dipstick proteinuria of 1+ does not necessarily represent
      significant nephropathy. There is little or no benefit in repeat testing outside
      of the low microalbuminuria range but compliance to such testing is poor.
      Screening for asymptomatic bacteriuria as part of microalbuminuria screening is
      of questionable value.

PMID- 12795662
TI  - The effect of cross-reactive epitope group matching on allocation and
      sensitization.
AB  - Some polymorphisms on HLA molecules are shared by different HLA types, which
      allows us to group HLA molecules into 'families' or groups based on the shared
      epitope. These cross-reactive epitope groups (CREGs) can be used as a basis for
      matching donors to recipients for renal transplantation. The current allocation
      system uses HLA-B,DR mismatching for assigning HLA points. Graft survival using
      newer immunosuppressive drugs still shows a significant improvement in graft
      survival for 0-mismatched donors (3-year survival approximately 90%) and a
      significantly worse graft survival for 5 and 6 HLA-mismatched donors (3-year
      graft survival approximately 75%). However, the difference in graft survival
      between 1-, 2-, 3- and 4-mismatched donors are nor significantly different from
      each other (80-85% survival at 3 year). This has led to a reassessment of the
      UNOS allocation system and the need to re-evaluate the role of HLA in graft
      survival, minority allocation, and HLA sensitization. One of the problems with
      the current algorithm is that very few recipients are actually getting well
      matched kidneys (approximately 3% get 1 mismatch and 10% get 2 mismatch).
      Transplant centres using the UNOS CREG variance (10 points awarded for 0 CREG, 0
      DR mismatches) were able to find matches at a sixfold higher rate over 0 BDR
      mismatches. The size of the list affects the likelihood of finding a good match
      and the CREG variance was more successful in larger transplant programs. The
      effect of HLA on equity in renal allocation is also being addressed. There is
      some concern that HLA points may be at least partially responsible for the
      decreased transplant rate in African Americans. The 1999 UNOS data showed that
      46.9% of the list were Caucasian, while 55.2% of the transplants were in
      Caucasian recipients. Conversely, African Americans made up 35.8% of the list and
      only 27% of the transplants went to African Americans. Since most of the donors
      were Caucasian (75.9% vs. 11.2%), it has been speculated that the Black
      population may be disadvantaged because they have less chance of getting HLA
      points. The impact of HLA on transplant rate is still being disputed and may not
      be a major factor since so few recipients actually benefit from the points given
      for BDR mismatches. However, CREG matching has the advantage of equalizing the
      HLA effect since rare HLA antigens are grouped with common HLA antigens sharing
      the same public epitopes. Another advantage for CREG matching is the protection
      from sensitization to HLA. The effect of HLA matching on sensitization is
      increased with each HLA match. Black recipients are more likely to be sensitized
      than Caucasians with the same level of mismatch. Also, once sensitized, Black
      recipients are less likely to get transplanted than Caucasians because of greater
      difficulty in finding a well-matched donor. Of patients transplanted with 0 CREG
      mismatched donors, 82% remained unsensitized to Class I, compared with less than
      60% in recipients who received greater than 2 BDR mismatches. The use of CREG
      matching in renal allocation offers better matching to a larger group of
      recipients and significantly reduces sensitization to HLA.

PMID- 12795661
TI  - Morphological and biochemical effects of immunosuppressive drugs in a capillary
      tube assay for endothelial dysfunction.
AB  - Immunosuppressive drugs common in clinical transplantation are known to have
      untoward effects on the vascular system. The effects of some drugs, notably
      cyclosporin A (CyA), have been studied on the vascular system, while those of
      others have not. In the vascular system, endothelial cells are the predominant
      cell type exposed to intravascular concentrations of immunosuppressive drugs. We
      therefore studied the effects of drugs common in clinical transplantation on
      endothelial cells in a capillary tube assay. The endothelial cells in the
      capillary tubes are morphologically more similar to those in the microvasculature
      than endothelial cells in monolayers. We studied the kinetics and extent of
      capillary tube formation and prostacyclin (PGI2) and endothelin-1 (ET-1) release
      from the in vitro capillaries to determine the morphological and biochemical
      effects of five immunosuppressive agents on endothelial function. We found a
      significant difference in the morphological and biochemical effects of the two
      common calcineurin inhibitors, CyA and tacrolimus (FK506) on capillary morphology
      in vitro. The former had a pronounced injurious effect on the morphology of the
      in vitro capillaries, while the latter did not. CyA also significantly increased
      ET-1 release by the capillaries, but FK506 did not. Mycophenolate mofetil (MMF)
      was the only other agent that had a moderately injurious effect on the morphology
      of the in vitro capillaries. Sirolimus (rapamycin) and dexamethasone, similar to
      FK506, had no effect on the capillary morphology. All these agents, except
      dexamethasone, increased PGI2 release. Our data suggest that CyA adversely
      affects the morphology of the microvasculature and that this is mediated, at
      least partly, by an increased ET-1 release by endothelial cells exposed to CyA.
      These findings describe a novel effect of CyA and MMF on endothelial cells that
      could be relevant to understanding the mechanisms of immunosuppressive drug
      mediated endothelial injury in clinical transplantation.

PMID- 12795663
TI  - Cardiac transplantation across a positive prospective lymphocyte cross-match in
      sensitized recipients.
AB  - BACKGROUND: Although there is an increasing body of evidence for a deleterious
      effect of mismatched donor HLA antigens on the outcome of human cardiac
      transplantation, the role of anti-HLA lymphocytotoxic antibodies remains
      controversial. Thus, their appearance after cardiac transplantation has been
      associated with poor outcome by some groups; whereas others have reported them to
      be of no clinical significance. Furthermore, their presence prior to cardiac
      transplantation has also been the subject of similarly conflicting reports. The
      deleterious effect of such pre-existing antibodies has been predicted by a
      positive lymphocyte cross-match (LCM), which, for most patients awaiting renal
      transplantation and in many requiring a cardiac allograft, leads to cancellation
      of the operation. The reason for undertaking the current study was to test the
      hypothesis that the constraints which a positive LCM result impose in preventing
      renal transplantation may not apply to orthotopic heart transplantation (OHT).
      PATIENTS AND METHODS: Four sensitized patients underwent OHT across a positive
      prospective LCM. Three were females, and one of those females also underwent
      cadaveric renal transplantation at the time of OHT. All four patients received
      aggressive early post-transplant immunosuppressive therapy, which included
      plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents
      (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin
      inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also
      received standard immunosuppressive therapy which included corticosteroids.
      Complement-dependent cytotoxicity (CDC) was used for the identification of anti
      HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of
      a panel of well-characterized T cells was considered sensitization, and required
      LCM to be performed prospectively, which test was also performed using the CDC
      technique. RESULTS: Three of the patients exhibited evidence suggestive of acute
      or hyperacute rejection in endomyocardial biopsy specimens by postoperative day
      (POD) 7. Two of the three patients with rejection also exhibited haemodynamic
      instability (elevated filling pressures and reduced cardiac index) on POD 1,
      which improved with inotropic support. One patient sustained a cardiac arrest on
      POD 7, and was successfully resuscitated without sequelae. All patients are now
      doing well, postoperatively (follow-up: 17-57 months) post-transplant. Two
      patients have normal left ventricular function and one patient has mild left
      ventricular dysfunction. Two have no further evidence of sensitization (PRA <
      10%). CONCLUSIONS: Although the number of patients in this study is small, the
      long-term successful outcome of OHT following positive prospective cross-matches
      suggests that such a test result, in contrast to the restraints it imposes on
      renal transplantation, may not be a contra-indication to transplantation of the
      human heart. If OHT proceeds after the LCM is reported positive, aggressive
      immunotherapy should not only be initiated early, but should also be targeted at
      humoral-vascular rejection in particular.

PMID- 12795664
TI  - Histopathological study of renal transplant artery stenosis: role of rejection
      and cold ischaemia time in the pathogenesis of intimal hyperplasia in an arterial
      allograft.
AB  - INTRODUCTION: Intimal hyperplasia of renal allograft arteries is a cause of
      hypertension and graft loss and the predisposing factors are poorly understood.
      We performed a histopathological study focusing on cold ischaemia time and
      immunological factors and their effect on the donor artery. METHODS: Primary
      renal artery branches were obtained from patients undergoing transplant
      nephrectomy for chronic rejection. Non-transplant patients undergoing nephrectomy
      served as controls. Clinical information including immunosuppression and
      rejection episodes, cold ischaemia time and graft survival were collected from
      the patients' charts. Collagen, smooth muscle cells, T cells, macrophages, and
      neutrophils were quantified using immunohistochemistry. The intima to media ratio
      was also calculated using imaging software. Statistical analysis was performed
      using linear regression and the Mann-Whitney test with P < 0.05 significant.
      RESULTS: Nine transplant patients and five controls were included. All transplant
      patients received maximum immunosuppression according to clinical standards. The
      median number of acute rejection episodes was 1 (range 0-5). Cold ischaemia time
      was 24.3 +/- 9.6 h (mean +/- SD). Mean allograft longeviy was 87.4 +/- 72.9
      months (mean +/- SD). The intima/media ratio in the transplant group was higher
      as compared with the control (P = 0.002). The same was true for intima collagen
      content (P = 0.001) and intima smooth muscle content (P = 0.036). Cold ischaemia
      time was 19.6 +/- 11.1 h (mean +/- SD) and did not correlate with intima/media
      ratio. Also the number of rejection episodes did not correlate with the
      intima/media ratio. CONCLUSION: Intimal hyperplasia in the allograft artery has a
      multifactorial aetiology. We were not able to establish an association between
      intimal hyperplasia and acute rejection episodes or length of cold ischaemia
      time. It appears that immunosuppression does not prevent the development of
      intimal hyperplasia.

PMID- 12795665
TI  - A pilot protocol of a calcineurin-inhibitor free regimen for kidney transplant
      recipients of marginal donor kidneys or with delayed graft function.
AB  - The worsening shortage of cadaver donor kidneys has prompted use of expanded or
      marginal donor kidneys (MDK), i.e. older age or donor history of hypertension or
      diabetes. MDK may be especially susceptible to calcineurin-inhibitor (CI)
      mediated vasoconstriction and nephrotoxicity. Similarly, early use of CI in
      patients with delayed graft function may prolong ischaemic injury. We developed a
      CI-free protocol of antibody induction, sirolimus, mycophenolate mofetil, and
      prednisone in recipients with MDK or DGF. METHODS: Adult renal transplant
      recipients who received MDK or had DGF were treated with a CI-free protocol
      consisting of antibody induction (basiliximab or thymoglobulin), sirolimus,
      mycophenolate mofetil, and prednisone. Serial biopsies were performed for
      persistent DGF. Patients were followed prospectively with the primary endpoints
      being patient and graft survival, biopsy-proven acute rejection, and sirolimus
      related toxicity. RESULTS: Nineteen recipients were treated. Mean follow-up was
      294 days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft
      survival was 93% and 93%, respectively. The only graft loss was due to primary
      non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last
      follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1),
      wound infection (2), thrombocytopenia (1). and interstitial pneumonitis (1).
      CONCLUSION: A CI-free protocol with antibody induction and sirolimus results in
      low rates of AR and PNF and excellent early patient and graft survival in
      patients with MDK and DGF. CI-free protocols may allow expansion of the kidney
      donor pool by encouraging utilization of MDK at high risk for DGF or CI-mediated
      nephrotoxicity.

PMID- 12795666
TI  - Delayed graft function may not adversely affect short-term renal allograft
      outcome.
AB  - INTRODUCTION: Delayed graft function (DGF) is commonly believed to adversely
      impact both short- and long-term renal allograft function. Because
      immunosuppressive therapy is commonly altered after DGF is identified,
      retrospective analyses are difficult to interpret. We therefore prospectively
      sought to examine the natural history of DGF in a controlled patient population
      under identical immunosuppressive protocols. METHODS: Adult patients undergoing
      cadaveric renal transplantation were treated with sequential triple drug
      immunotherapy. High-dose steroids were administered in the operating room and
      rapidly tapered to 20 mg prednisone by post-operative day (POD) 6. Cyclosporine
      (CsA) microemulsion was begun on POD 1, and dosed asymmetrically at 12-h
      intervals to reach a daytime Cav of 650 ng/mL (utilizing 2-h and 6-h levels),
      while PM doses were adjusted to an AM trough of 300 ng/mL. Mycophenolate (1000 mg
      q12 h) was added on POD 3 in most patients and discontinued after 3 months. No
      induction agents were used. All patients were followed for at least 6 months.
      RESULTS: Sixty consecutive patients received 64 allografts (four double grafts).
      In all, 17 patients required dialysis and were considered to have DGF. Eight of
      these patients received marginal organs turned down by at least one other centre.
      Cold ischaemia time was significantly longer in patients with DGF (24 h vs. 19 h,
      P < 0.01) All patients were treated as planned and there were no major protocol
      violations. One patient had primary non-function and was excluded from analysis.
      CsA trough and Cav values were similar between groups. Mean serum creatinine
      levels (mg/mL) fell more slowly in patients with DGF but there was no significant
      difference by 3 months (1.7 vs. 1.5) and the creatinine clearance was not
      significantly different between the groups after 1 year (71 cm3/min in DGF vs. 61
      cm3/min, P = 0.13). Our data demonstrate that alterations in routine
      immunosuppressive strategies may not be necessary to achieve equivalent outcomes
      in patients with DGF.

PMID- 12795667
TI  - Laparoscopic procurement model for living donor liver transplantation.
AB  - BACKGROUND/AIMS: Noting the contribution to renal transplantation by the
      introduction of the laparoscopic approach to donor nephrectomy, we investigated
      the possibility of performing a laparoscopic hepatic lobe procurement with the
      goal of performing a live donor liver transplantation. We describe our technique
      and determine its feasibility for such a goal. METHODS: The surgical technique
      was developed over a series of 12 adult female pigs and adapted in two human
      cadavers. The technique included pneumoperitoneum with CO2, mobilization of the
      liver, and transection of the parenchyma into right and left lobes with a
      laparoscopic cavitron ultrasonic aspirator. The vascular inflow and outflow
      structures (hepatic artery, portal vein, hepatic veins) of the anatomical
      specimen being procured were preserved undisturbed during the hepatic
      transection. No temporary vascular occlusion techniques were utilized. The
      vascular structures were stapled and sectioned just prior to removal of the
      specimen. RESULTS: Hepatic lobectomies were successfully performed
      laparoscopically. Vascular and biliary structures were preserved to allow for
      subsequent transplantation. Operative time from establishment of pneumoperitoneum
      to lobe procurement was under 4 h. CONCLUSIONS: This study demonstrates the
      feasibility of laparoscopic living donor procurement for liver transplantation,
      from both a technical and a physiological perspective.

PMID- 12795668
TI  - Recipient outcome following living donor kidney transplantation using kidneys
      procured laparoscopically.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy is becoming increasingly popular
      as it has been shown to minimize donor morbidity, length of hospital stay and
      length of time to return to work. Initial experience suggested that kidneys
      procured laparoscopically had higher rates of delayed graft function and ureteric
      complications but with increasing experience, these complications have become
      less common. METHODS: Retrospective chart review of all patients who underwent
      living donor kidney transplant using kidneys procured laparoscopically at our
      centre was performed. From the initiation of the laparoscopic donor nephrectomy
      programme at our institution in November 1998 until February 2002, we performed
      71 living donor kidney transplants (69 kidneys procured laparoscopically and two
      procured by open donor nephrectomy after failed laparoscopic approach). Donor
      left kidney was used in all except in one patient. Mean duration of warm
      ischaemia time was 206 +/- 79 s. RESULTS: The mean age of the recipients was 42
      +/- 15 years (range 1-68) including five paediatric recipients (age < 18 years).
      There were 48 males and 23 females. Nine (13%) were retransplants (seven second
      transplants and one each of third and fourth transplants). Two patients died with
      functioning grafts and four patients lost the graft (three thrombosis, one
      anastomotic rupture). No patient developed ureteric complications. The incidence
      of delayed graft function (need for dialysis in the first week post-transplant)
      was 4%. Patient and graft survival rates (actual) were 97% and 91%, respectively.
      Mean length of hospital stay was 9 +/- 7 days (median 7 days). CONCLUSIONS:
      Recipient outcome is not compromised and excellent results can be achieved with
      living donor kidney transplantation using laparoscopically procured kidneys.

PMID- 12795669
TI  - Point-of-care testing in an organ procurement organization donor management
      setting.
AB  - PURPOSE: Our organ procurement organization (OPO) evaluated the clinical and
      financial efficacy of point-of-care testing (POCT) in management of our deceased
      organ donors. METHODS: Before we implemented point-of care testing with the i
      STAT into routine clinical donor management, we compared the i-STAT result with
      the result from the respective donor hospital lab (DHL) for certain analytes on
      15 consecutive donors in our OPO from 26 March to 14 May 2001. The financial
      impact was studied by reviewing 77 donors from July 2001 to March 2002. RESULTS:
      There was a strong correlation for each analyte between the POC and DHL test
      results with r-values as follows: pH 0.86; PCO2 = 0.96; PO2 = 0.98; sodium =
      0.98; potassium = 0.95; chloride = 0.94; BUN = 0.98; glucose = 0.92; haematocrit
      = 0.87 and creatinine = 0.95. Since our OPO coordinators began using i-STAT in
      their routine clinical management of organ donors, they can now more quickly
      maximize oxygenation and fluid management of the donor and make extra-renal
      placement calls sooner. Finally, since we are no longer being billed for the
      testing performed on the i-STAT, average financial savings to our OPO are US
      dollars 733 per case. CONCLUSIONS: Point-of-care testing in management of our OPO
      donors provides a result that is equivalent to that of the donor hospital lab,
      has quicker turn-around time than the donor hospital laboratory, allowing more
      immediate clinical management decisions to be made so that extra-renal offers may
      begin sooner.

PMID- 12795670
TI  - Cadaveric organ donor recruitment at Los Angeles County Hospital: improvement
      after formation of a structured clinical, educational and administrative service.
AB  - BACKGROUND/AIMS: There remains a critical shortage of cadaveric organs. At a
      large inner city level one trauma centre, several strategies were devised and
      combined to (a). optimize the physiologic status of potential donors, (b).
      promote awareness of the donation process among health care professionals and
      (c). perform quality control on the organ donation system - all in an effort to
      improve organ donation rates. Resuscitative and maintenance protocols were
      devised and implemented through a multidisciplinary team approach for patients
      diagnosed with brain death. We report the effect this approach has had on organ
      donation in a single centre. METHOD: A death record review (DRR) by the local
      organ procurement agency (OPO) was used to identify the number of patients
      diagnosed with brain death at Los Angeles County Hospital each year from 1995
      through 2001. Data were collected to determine the number of these potential
      donors that eventually underwent organ donation. Data were collected for two time
      intervals: Phase I (1995-98) and Phase II (1999-2001). During Phase I, there was
      no focused institutional programme for the approach to potential donors. During
      Phase II, an institutional programme including the following characteristics was
      implemented: 1). donor resuscitation protocol, 2). assignment of a dedicated OPO
      coordinator liaison to interact with families, hospital personnel and the
      coroner's office, 3). assignment of the primary role of stabilization and care of
      potential donors and the integration of all medical services to the trauma
      service, and 4). biweekly conferences to review policies, protocols, and outcomes
      of donor management strategies. RESULTS: From 1995 to 2001 there was a large
      increase in patient referrals for donor evaluation from 86 (Phase I) to 124
      (Phase II). There was a smaller increase in the number of suitable donors: Phase
      I (mean: 51/year) and Phase II (mean: 63/year). There was, however, an increase
      in the mean number of actual organ donors from 14.2/year to 25.7/year from Phase
      I to Phase II and an increase in organs donated from 29 to 49. Organ donor
      declines decreased from 53% (Phase I) to 39% (Phase II). CONCLUSIONS: Strategies
      to increase the number of cadaveric organs available for organ transplantation
      are crucial. A strategy combining prompt identification of potential organ
      donors, institution of resuscitative protocols, a multidisciplinary team
      approach, educational activities and utilization of personnel expert in organ
      procurement led to a marked increase in the number of organ donors and the number
      of organs donated at a single institution. Wider application of this approach
      should prove successful in increasing organ donation in a similar fashion in
      other institutions.

PMID- 12795671
TI  - Cold ischaemia time added to kidneys can be minimized by completing the final
      cross-match before organs are taken from the operating room.
AB  - Minimizing the amount of cold ischaemia time (CIT) added to cadaveric kidneys
      before their transplantation is an important goal since longer CIT is associated
      with worse long-term graft outcome. Our organ procurement organization (OPO) and
      HLA laboratories have taken the approach of performing the histocompatibility
      testing, including the final cross-match, as early in the donor process as
      possible. METHODS: The data in this study were collected from all consecutive
      final cross-matches done for cadaveric kidney (n = 113) and simultaneous pancreas
      + kidney (SPK) (n = 25) transplants done with organs recovered from donors in the
      Midwest Transplant Network OPO from 1 January 2001 to 9 May 2002. We evaluated
      the time the final cross-match was completed from when the kidneys from that
      donor were taken from the operating room (OR) and compared that time with CIT.
      RESULTS: For kidney transplants, 72% of the final cross-matches were complete
      before the kidneys were taken from the OR. The CIT of that group (10.4 +/- 3.8 h)
      was significantly lower than that of the group of kidney transplant patients
      whose final cross-match was done after the kidneys were taken from the OR (15.5
      +/- 5.8 h) (P < 0.001). Similarly, for SPK transplants, 88% of the final cross
      matches were completed before the organs left the OR and the CIT of that group
      (10.2 +/- 3.4 h) was less than in the group whose final cross-match was done
      after the organs left the OR (14.3 +/- 4.8 h) (P > 0.1). CONCLUSIONS: These data
      show that the practice of completing the final cross-match as early in the donor
      process as possible helps to minimize the amount of cold ischaemia time added to
      the kidneys and pancreata before transplantation. That should reduce the
      detrimental influence that longer CIT has on short- and long-term function in
      kidney as well as SPK transplantation.

PMID- 12795672
TI  - Management of complications of simultaneous kidney-pancreas transplantation with
      temporary venting jejunostomy.
AB  - The majority of simultaneous kidney-pancreas (SPK) transplants are being
      performed with portal-enteric drainage, which does not allow easy access to the
      donor pancreas. By adding a temporary venting jejunostomy (TVJ) we have been able
      to closely monitor patients for bleeding, anastomotic leak and rejection.
      METHODS: Retrospective chart review of 29 patients undergoing SPK with PE
      drainage from December 1996 to December 2001. RESULTS: Median follow-up was 32
      months. Patient, kidney and pancreas graft survival were 93%, 90% and 93%,
      respectively. The most common early complications were wound infections and
      bleeding. No patient suffered vessel thrombosis. The most common late (greater
      than 3 months post-transplant) complication was gastro-intestinal bleeding.
      Adequate tissue was obtained for biopsy in 100% of patients with suspected
      pancreatic rejection. The TVJ allowed one patient to undergo donor pancreas ERCP
      that demonstrated the site of a pancreatic duct leak. Duodenal stump leak and
      anastomotic bleeding were diagnosed in one patient each via the TVJ. The median
      time to takedown of the TVJ was 14 months. CONCLUSION: TVJ allows patients an
      easy method of graft surveillance, is well tolerated, and has an acceptable
      complication rate. The TVJ allows access to diagnose anastomotic leak, cauterize
      bleeding mucosa, perform ERCP and biopsy the pancreas allograft.

PMID- 12795673
TI  - Long-term experience with simultaneous kidney-pancreas transplantation with
      portal-enteric drainage and tacrolimus/mycophenolate mofetil-based
      immunosuppression.
AB  - Refinements in surgical techniques and advances in clinical immunosuppression
      have led to steadily improving results in pancreas transplantation (PTX).
      Although there is renewed interest in enteric exocrine drainage, most PTXs are
      performed with systemic venous delivery of insulin. To improve the physiology of
      PTX, we developed a novel technique of portal venous delivery of insulin and
      enteric drainage of the exocrine secretions (portal-enteric [P-E]). The purpose
      of the study was to analyse outcomes in patients undergoing PTX with P-E drainage
      and contemporary immunosuppression. MATERIALS AND METHODS: From January 1997
      through September 2002, we performed 67 primary simultaneous kidney-PTXs (SKPT)
      with P-E drainage. Maintenance immunosuppression consisted of tacrolimus (TAC),
      mycophenolate mofetil (MMF) and steroids. No antibody induction therapy occurred
      in 33 patients (49%) with the remainder receiving daclizumab (n = 15),
      basiliximab (n = 2), or thymoglobulin (n = 14) induction therapy. The patient
      group included 38 males and 29 females with a mean age of 39.7 year (range 23-58)
      and a mean duration of pretransplant diabetes of 24.5 year (9-46). Fourteen
      patients (21%) were African-American. RESULTS: The mean waiting time for SKPT was
      3.3 months (range 0.1-10). Mean kidney and pancreas cold ischaemia times were
      15.1 and 15.4 h, respectively. Patient, kidney and pancreas graft survival rates
      were 97%, 92.5% and 82%, respectively, with a mean follow-up of 20 months (range
      1-56). Two deaths (one sepsis, one cardiac event) occurred at 1 month after SKPT;
      both patients died with functioning grafts (DWFG). Three patients (4.5%) had
      delayed renal allograft function and received temporary dialysis after SKPT. Five
      kidney graft losses occurred (two DWFG, one thrombosis, two chronic rejection).
      All but four patients (6%) had immediate PTX function. A total of 12 pancreas
      graft losses occurred (two DWFG, five thrombosis, five chronic rejection). The
      incidence of acute rejection was 28%, but no grafts were lost due to isolated
      acute rejection. The incidence of major infection was 51%, but only five patients
      (7.5%) developed cytomegalovirus infection. A total of 19 patients (28%)
      underwent early relaparotomy within 3 months of SKPT. The composite endpoint of
      no rejection, graft loss, or mortality was attained by 63% of patients. At
      present, 58 patients (87%) are both dialysis and insulin-independent (including
      four retransplants). CONCLUSION: These findings suggest that SKPT with P-E
      drainage and contemporary immunosuppression may result in excellent intermediate
      term outcomes.

PMID- 12795674
TI  - The impact of patient education and psychosocial supports on return to normalcy
      36 months post-kidney transplant.
AB  - INTRODUCTION: Improvements in immunosuppression, and expansion of
      immunosuppression coverage by Medicare now necessitate beginning to define
      success in transplantation from a holistic or whole person approach rather than
      the historical emphasis on patient and graft survival alone. In a new transplant
      environment, efforts will have to be made to redefine practice so that kidney
      transplant recipients are prepared for 10 or more years of life with a
      transplanted graft. Currently, 83% of transplanted patients will never return to
      work. The purpose of this study is to determine how targeted education and
      specific psychosocial supports affect the transplant patient's return to normalcy
      36 months after kidney transplant. Normalcy is defined as age and socially
      appropriate activities for that patient. METHODS: This is a synopsis of a 1-year
      cross-sectional study of 51 patients who received kidney transplants in 1999 at
      or near their 36-month anniversary date. Thirty-six months was chosen because
      this is the date when most patients will lose their Medicare coverage for
      immunosuppression. In 1999, a multidisciplinary plan was initiated to restructure
      the transplant recipient evaluation process, such that education about kidney
      transplantation and expectations for return to normalcy were addressed at the
      initial 'introduction to transplant session'. These measures were then
      consistently reinforced with each subsequent contact. At the second contact,
      written verbal plans for medication purchase and return to normalcy were
      identified. The team made a conscious effort to develop relationships with the
      recipients and their significant others, with the intention to better empower
      them to return to normalcy post-transplant. These measures (education and
      psychosocial support) were this study's independent variables. At 36 months, all
      patients were contacted by telephone and a 12-item questionnaire was
      administered. The questionnaire sought information about the study's dependent
      variables - employment and insurance status, pre- and post-transplant. RESULTS:
      In this study, 44% of pre-transplant patients were non-disabled compared with 62%
      of transplanted patients at 36 months post-transplant (P = 0.06, Chi square). Non
      disabled includes persons who are employed, homemakers, students, retired or
      otherwise involved in age and socio-economically appropriate activities. Pre
      transplant, 23% of recipients utilized Medicare and Medicaid for health insurance
      coverage. At 36 months post-transplant, only 11 or 20% of patients were dependent
      on Medicare and Medicaid. Pre-transplant, 17 recipients had private insurance
      coverage vs. 23 patients 36 months later (P < 0.02, Chi square). Fifty-six per
      cent of the patients received a living donor transplant. CONCLUSION: A targeted
      multidisciplinary programme of education and psychosocial support that emphasizes
      return to normalcy and non-disability, beginning with the first exposure to
      transplant and continuing throughout the first 6 months post-transplant, yielded
      high rates of return to normalcy for kidney transplant recipients.

PMID- 12795676
TI  - Implications of the advent of homozygous alpha l, 3-galactosyltransferase gene
      deficient pigs on transmission of infectious agents.

PMID- 12795677
TI  - Toward clinical trials of islet xenotransplantation.

PMID- 12795678
TI  - Pathology of xenograft rejection: a commentary.
AB  - Trends in solid organ xenograft pathology are presented, with the focus on pig-to
      nonhuman primate models. A simplified classification of rejection is followed,
      including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR),
      and acute cellular xenograft rejection (ACXR). The main components in HAR are
      natural xenoreactive antibodies in combination with complement activation. This
      is evident from the prevention of HAR in recipients in whom either antibodies or
      complement activation is depleted or inhibited. However, these strategies
      generally fail to prevent AHXR, which occurs later. AHXR is a multifactorial
      process in which natural and elicited antibodies may play roles, possibly in
      conjunction with complement, coagulation factors, and white blood cells. A main
      target appears to be the microvasculature which, in kidney grafts, is associated
      with a glomerular thrombotic microangiopathy. It is not clear to what extent
      species-specific physiologic disparities in complement and coagulation processes
      may play a role, separate from antibody-initiated processes. As rejection of
      solid organ xenografts is currently from AHXR, ACXR has not yet received close
      attention. In addition to intragraft rejection events, systemic complications
      following host-graft interactions have emerged, including (often fatal)
      consumptive coagulopathy and immune complex disease. It is anticipated that
      rejection processes will change when pigs with new genetic modifications become
      available. For instance, the precise role of natural antibodies to Galalpha1,3Gal
      will be able to be distinguished from other factors when pigs that lack the
      target antigen are available, and their organs can be evaluated in large animal
      xenotransplantation models.

PMID- 12795679
TI  - Maintenance triple immunosuppression with cyclosporin A, mycophenolate sodium and
      steroids allows prolonged survival of primate recipients of hDAF porcine renal
      xenografts.
AB  - To date, the best results in life-supporting pig-to-primate renal
      xenotransplantation have been obtained in recipients exposed to long-term
      immunosuppression with cyclophosphamide. As this agent is frequently associated
      with side-effects, we have explored the potential of a mycophenolate sodium-based
      maintenance immunosuppression in this model. Human decay-accelerating factor
      (hDAF) transgenic kidneys were transplanted into splenectomized and bilaterally
      nephrectomized cynomolgus monkeys immunosuppressed with mycophenolate sodium,
      cyclosporin A and steroids, and exposed to a brief induction course with
      cyclophosphamide (up to four doses). After transplantation, the primates were
      monitored daily for biochemical and haematological evaluations and for the
      measurements of haemolytic anti-pig antibodies (APA). A detailed histological
      analysis of each explanted graft was also performed. All the animals showed very
      poor initial graft function but survived for up to 51 days. In contrast to our
      previous studies in xenograft recipients on long-term immunosuppression with
      cyclophosphamide, minimal or no circulating xeno-directed antibodies, as measured
      by the evaluation of APA titres, were detected in this series although some
      degree of acute humoral rejection was observed in all the explanted grafts and
      was the primary cause of graft failure. Furthermore, in addition to areas of
      humorally mediated graft damage, we have observed for the first time areas with
      exclusive and prominent infiltration by CD2+ and CD8+ mononuclear cells
      presenting patterns compatible with tubulitis, glomerulitis and arteritis, which
      we have called acute cellular xenograft rejection (ACXR). In addition, CD68+
      infiltrating macrophages and CD20+ B-cells were also present. This study
      demonstrates that a triple maintenance immunosuppression with mycophenolate
      sodium, cyclosporin A and steroids is a viable alternative to a cyclophosphamide
      based immunosuppression to obtain prolonged survival of porcine organs
      transplanted into primates. However, a more stringent control of antibody forming
      cells remains essential to further extend the survival of xenografts in this
      model. In addition, the use of the immunosuppressive regimen reported here in the
      primate is associated with the occurrence of a new category of cell-mediated
      xenograft injury (ACXR) whose significance has yet to be clarified.

PMID- 12795681
TI  - Treatment with a short course of LF 15-0195 and continuous cyclosporin A
      attenuates acute xenograft rejection in a rat-to-mouse cardiac transplantation
      model.
AB  - Searching for a novel immunosuppressive agent to effectively prevent acute
      vascular rejection (AVR) is essential for success in clinical
      xenotransplantation. We previously reported that Lewis rat hearts transplanted
      into BALB/c mice developed typical AVR in 6 days. The present study was
      undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive
      analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac
      xenograft model. We transplanted 2-week old Lewis rat hearts into BALB/c mice.
      Four groups were included in this study: untreated recipients and cyclosporin A
      (CsA) treated recipients were controls; LF 15-0195 treated recipients or LF 15
      0195 combined with CsA treated recipients were experimental groups. Mouse
      recipients received either LF 15-0195 2 mg/kg subcutaneously from day-1 to post
      operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint
      rejection, or the two drugs in combination. We observed that high dose CsA did
      not inhibit AVR and the graft was rejected in 11.3 +/- 1.9 days. Graft histology
      and immunohistology showed typical AVR, characterized by interstitial hemorrhage,
      intravascular fibrin deposition, thrombosis, and massive deposition of anti-rat
      immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies
      (xAbs) were markedly elevated in these animals as well. In contrast, we observed
      that treatment with LF 15-0195 alone significantly prolonged graft survival to
      19.3 +/- 0.7 days. Notably, xAbs were significantly decreased and the rejection
      pattern of these grafts was cell-mediated rejection (CMR), instead of AVR. When
      CsA was combined with LF 15-0195, the graft mean survival time was further
      increased to 58.5 +/- 17.3 days. Antibody production and T-cell infiltration were
      significantly inhibited at the terminal stages of graft survival and pathology
      showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and
      14 demonstrated that LF 15-0195 either alone or combined with CsA completely
      inhibited antibody production. However, intragraft infiltration by Mac-1 positive
      cells including natural killer cells, macrophages and granulocytes in LF 15-0195
      treated recipients was similar to that of untreated recipients. We conclude that
      LF 15-0195 effectively prevented AVR by markedly inhibiting the production of
      anti-donor IgG xAbs. Also, treatment with short course LF 15-0195 and continuous
      CsA significantly reduced T-cell infiltration. Studies to test this therapy in
      inhibiting AVR in a pig-to-non-human primate xenotransplantation model are
      underway.

PMID- 12795680
TI  - Intragraft cytokine mRNA expression in rejecting and non-rejecting vascularized
      xenografts.
AB  - BACKGROUND: The aim of the present study was to further investigate the
      characteristics of both graft-infiltrating cells and splenocytes during acute
      vascular rejection (AVR), cell-mediated rejection and non-rejection of
      vascularized concordant xenografts, by analysing both proinflammatory
      [interleukin-1beta (IL-1beta) and tumour necrosis factor (TNF-alpha)] and more
      specific [(IL-2, IL-4, IL-10, IL-12p40 and interferon-gamma (IFN-gamma)]
      cytokines. A parallel investigation was made of the antibody response of IgM and
      IgG to the xenografts. METHODS: Mouse hearts were heterotopically transplanted to
      the neck vessels of recipient rats. Grafts, spleens and sera were collected from
      untreated (AVR) and cyclosporin A (CyA) treated animals on day 2 after
      transplantation. Organs from rats treated with 15-deoxyspergualin (DSG) or CyA
      and DSG in combination were harvested on both day 2 and day 8. Grafts from DSG
      treated rats undergo cell-mediated rejection and stop beating on day 9 and forth,
      while CyA + DSG treatment results in long-term graft survival. Real-time
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was applied
      for analysis of intragraft and splenic cytokine messenger RNA (mRNA) expression.
      The phenotypes of the graft infiltrating cells were characterized by
      immunohistochemistry. The antibody response was investigated by means of
      immunofluorescence, haemagglutination and flow cytometry. RESULTS: All the
      studied cytokines (IL-1beta, IL-2, IL-4, IL-10, IL-12p40, IFN-gamma and TNF
      alpha) were up-regulated in the grafts from rejecting untreated (day 2) and DSG
      treated animals (day 8) in comparison with grafts from CyA + DSG treated animals
      (day 8). On day 2 under immunosuppression with CyA, DSG or CyA + DSG no or low
      cytokine mRNA levels were found. The mRNA levels of IL-2, IL-4 and IFN-gamma in
      the spleens were suppressed under both DSG- and CyA + DSG treatment on day 8.
      Immunofluorescence showed deposits of both IgM and IgG in grafts from untreated,
      CyA-treated (day 2) and DSG-treated (day 8) animals, while CyA + DSG treatment
      diminished these deposits on both day 2 and day 8. No circulating antibodies were
      identified in either group. CONCLUSION: We hereby conclude that both AVR on day 2
      and cell-mediated rejection on day 8 (under DSG treatment) in a concordant
      cardiac mouse-to-rat xenotransplantation model are associated with an increase of
      proinflammatory cytokines, T helper 1 (Th1)-associated cytokines as well as IL
      10, while immunosuppression with CyA + DSG diminishes the levels of all examined
      cytokines. Grafts undergoing AVR or cellular rejection are subjected to deposits
      of both IgM and IgG, although circulating donor specific antibodies are
      undetectable in serum.

PMID- 12795682
TI  - Detection of porcine endogenous retrovirus in cultures of freshly isolated
      porcine bone marrow cells.
AB  - Pigs are under consideration as possible sources of organs for
      xenotransplantation in humans. The induction of hematopoietic microchimerism
      through xenotransplantation of source animal hematopoietic cells has been
      suggested as a means to induce tolerance in potential recipients. Because all
      porcine cells contain genetic information for porcine endogenous retrovirus
      (PERV), coculture techniques, reverse transcriptase (RT) and reverse
      transcriptase-polymerase chain reaction assays were used to determine whether
      infectious PERV is released from fresh porcine bone marrow cells cultured in the
      presence or absence of porcine cytokines. Human embryonic kidney cell line, HEK
      293 cells cocultured with porcine bone marrow cells were positive for PERV RNA
      but never became positive for viral RT activity, suggesting the PERV infection
      was not productive. In contrast, high levels of RT activity was detected in
      porcine ST-IOWA cells after coculture, demonstrating that these cells became
      productively infected. PERV was released from cultured porcine bone marrow cells
      without stimulation, and combinations of the porcine hematopoietic cytokines,
      interleukin-3, granulocyte macrophage-colony stimulating factor and stem cell
      factor had no additional effect on the infectivity or in vitro tropism of
      released PERV virions.

PMID- 12795683
TI  - Methods for the exclusion of circoviruses and gammaherpesviruses from pigs.
AB  - The use of porcine tissues is being developed as a means to alleviate the
      shortage of allogeneic tissues and organs available for transplantation. To
      reduce the possibility of a microorganism of pigs being inadvertently transferred
      to the recipient of the xenograft, recommendations have been published on the
      microbiological specifications for organ source pigs. The porcine circoviruses
      (PCV1 and PCV2) and porcine lymphotropic herpesviruses (PLHV1 and PLHV2) are two
      infectious agents of pigs which are considered to be of significance for the
      microbiological safety of xenotransplantation. To ensure the exclusion of these
      microorganisms from animals destined for use under clinical conditions, reliable
      breeding methodologies are required. We investigated the efficiency of
      established derivation procedures for the removal of PCV and PLHV. In comparison
      with conventionally reared pigs, caesarian and barrier derived animals showed a
      markedly reduced prevalence of PCVs and PLHVs. Our results indicate that the
      derivation of animals free of both of these microorganisms is achievable and will
      enhance the microbiological safety of xenotransplantation.

PMID- 12795684
TI  - Approaching virus safety in xenotransplantation: a search for unrecognized
      herpesviruses in pigs.
AB  - The identification of porcine viruses so far unrecognized is required to minimize
      virus-related risks associated with xenotransplantation. We used a pan-herpes
      consensus polymerase chain reaction assay to search for unrecognized porcine
      species of the Herpesviridae. The assay targets conserved regions of the
      herpesvirus DNA polymerase (DPOL) gene, using primers that were modified to
      diminish the assay's recognition capacity for the highly prevalent porcine
      lymphotropic herpesviruses 1, 2 and 3 (PLHV-1, -2, -3), without substantially
      lowering the universal detection capacity of the assay. Analysis of 495 porcine
      blood and tissue samples from 294 animals, including 35 samples from 20
      immunosuppressed pigs, resulted in the amplification of 128 herpesviral DPOL
      sequences. Sequence analysis attributed 127 of the amplimers to the known porcine
      herpesviruses (PLHV-1, -2, -3; porcine cytomegalovirus; pseudorabiesvirus). In
      none of the pig samples analyzed here, evidence was obtained for the presence of
      additional novel porcine herpesvirus species. Therefore we conclude that pigs
      bred for the purpose of xenotransplantation pose a negligible risk of
      transmitting presently unrecognized herpesviruses to organ recipients.

PMID- 12795685
TI  - Depletion of anti-Gal antibodies by the intravenous infusion of Gal type 2 and 6
      glycoconjugates in baboons.
AB  - BACKGROUND: Natural anti-Gal antibodies (NAb) to Gal epitopes play a key role in
      the rejection of pig cells or organs transplanted into primates. We have
      investigated the effect on NAb return after extracorporeal immunoadsorption (EIA)
      of the continuous intravenous (i.v.) infusion of (i) bovine serum albumin
      conjugated to Gal type 6 oligosaccharides (BSA-Gal) or (ii) a poly l-lysine
      backbone conjugated to Gal type 2 or 6 oligosaccharides (PLL-Gal). METHODS:
      Porcine mobilized peripheral blood progenitor cells (PBPC) obtained by
      leukapheresis from MHC-inbred miniature swine (n = 9) were infused intravenously
      (i.v.) into baboons: Group 1 baboons (n = 4) received whole body and thymic
      irradiation, splenectomy, antithymocyte globulin, cobra venom factor,
      cyclosporine, mycophenolate mofetil, anti-CD154mAb, porcine hematopoietic growth
      factors, and EIA before transplantation of high doses (2 to 4 x 1010 cells/kg) of
      PBPC; Group 2 baboons (n = 3) received the Group 1 regimen plus a continuous i.v.
      infusion of BSA-Gal for up to 30 days; Group 3 baboons (n = 5) received the Group
      1 regimen plus a continuous i.v. infusion of PLL-Gal type 2 (n = 2) or both PLL
      Gal types 2 and 6 (n = 3) for up to 30 days. RESULTS: Group 1: NAb returned to
      pre-PBPC levels within 20-30 days, but there was no induction of antibody to Gal
      or non-Gal determinants; Group 2: NAb was undetectable or at very low level
      during BSA-Gal therapy. In one baboon, however, IgG to Gal type 2, but not to
      type 6, returned during BSA-Gal therapy; Group 3: NAb was undetectable or at very
      low level during PLL-Gal therapy. In two baboons that received PLL-Gal type 2,
      NAb to Gal type 6, but not to type 2, returned during PLL-Gal treatment. Two of
      five baboons, however, developed systemic infection. Four of five baboons died
      within 14 days; autopsy revealed focal hemorrhagic injury to their hearts, lungs,
      and small intestines, with histologic abnormalities that varied between animals
      from hemorrhage and/or thrombosis in some organs (heart, lungs, or intestine) to
      signs of infections (bacteria in intestine, cytomegalovirus in liver).
      CONCLUSIONS: (i) BSA-Gal and PLL-Gal therapy maintained depletion of NAb. (ii)
      Some heterogeneity in specificity of NAb was identified, indicating that the
      infusion of a combination of Gal type 2 and 6 glycoconjugates may be required.
      (iii) The addition of PLL-Gal to the immunosuppressive regimen was associated
      with a high incidence of morbidity and mortality without a clear histopathologic
      entity underlying the cause of death.

PMID- 12795686
TI  - Ajoene inhibits the activation of human endothelial cells induced by porcine
      cells: implications for xenotransplantation.
AB  - Ajoene, is an organosulfur compound derived from garlic that strongly inhibit
      platelet aggregation, proliferation of human lymphocytes induced by
      phytohemagglutinin, and in general, blocks membrane-mediated signaling of cell
      activation. As a thrombotic microangiopathy frequently complicates procedures
      designed to induce pig-to-baboon chimerism by infusion of large amounts of pig
      progenitor cells in baboons, it was thought that ajoene might be useful to
      prevent such complication. For such purpose, we studied the effects of ajoene on
      the activation of human umbilical vein endothelial cells (HUVEC) induced by pig
      peripheral blood mononuclear cells (p-PBMC). Co-cultures of p-PBMC with HUVEC
      results in activation of the HUVEC as shown by over-expression of E-selectin and
      vascular cells adhesion molecule-1 (VCAM-1). Ajoene (25 microm) strongly inhibits
      HUVEC activation induced by tumor necrosis factor-alpha (TNF-alpha) or p-PBMC as
      shown by a down regulation of VCAM-1 and of E-selectin expression. After 5 or 8 h
      of pre-treatment with Ajoene, HUVEC incubated with TNF and p-PBMC showed an E
      selectin or VCAM-1 expression, respectively, at levels similar to the positive
      control indicating that the inhibitory effect is transient. Ajoene at
      concentration of 25 microm or lower did not affect HUVEC viability. Based on the
      finding that Ajoene has a strong, although transient, inhibitory effect on the
      activation of the endothelium induced by pig cells and its known anti-platelet
      activity, it is suggested that this garlic compound could be useful to prevent
      the development of microangiopathy and thrombotic disorders seen in primates
      infused with pig cells.

PMID- 12795687
TI  - Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic
      derivative, ajoene.
AB  - BACKGROUND: The infusion of pig growth factor-mobilized peripheral blood
      leukocytes (containing 1 to 2% progenitor cells) (pPBPC) into baboons is
      associated with a thrombotic microangiopathy, which results from a direct effect
      of these pig cells on platelet aggregation. Ajoene is a synthetic derivative of
      garlic that inhibits aggregation of human platelets induced by all known agents.
      To assess its potential use in models of xenotransplantation, this agent was
      tested for its effect on baboon platelet aggregation in vitro and in vivo.
      METHODS:  IN VITRO STUDIES: Baboon platelet aggregation assays, using adenosine
      diphosphate (ADP) (20 or 40 microm) or collagen (12.5 microg/ml), were performed
      after incubation with ajoene (0 to 150 microg/ml) or dipyridamole (0 to 200
      microg/ml). Platelets were also incubated with pPBPC (5 x 10(6) cells) without or
      with ajoene in the absence of a known agonist. In vivo studies: Baboons received
      either a single intravenous dose of ajoene (10 to 25 mg/kg) or dipyridamole (0.8
      mg/kg), or repeated doses of both agents at 2 to 3 h intervals. Platelet-rich
      plasma was obtained for platelet aggregation assays at time points up to 4 h post
      drug administration. RESULTS: In vitro, platelet aggregation was inhibited by 95%
      (ADP assay) and 89% (collagen assay) by ajoene at concentrations of > or =75
      microg/ml. Dipyridamole had no effect at concentrations of <100 microg/ml, but
      inhibited aggregation almost completely at higher concentrations. Ajoene
      inhibited the aggregation caused by pPBPC by 33 to 50%. In vivo, platelet
      aggregation was completely inhibited for 2 h by ajoene at 25 mg/kg. Dipyridamole
      at 0.8 mg/kg reduced aggregation by 20% for 15 min, but the effect was lost by 60
      min. In combination, the two agents prolonged inhibition marginally. Repeated
      doses of both agents at 2 h intervals maintained complete inhibition of
      aggregation, but did not do so when the interval between doses was extended to
      2.5 or 3 h. Combined therapy was not associated with any bleeding complications.
      CONCLUSIONS: Although ajoene is a powerful inhibitor of platelet aggregation, the
      need for repeated administration and its partial effect on pPBPC-induced platelet
      aggregation would suggest that it may be of only limited value in preventing the
      thrombotic microangiopathy that develops when pPBPC are infused into baboons.
      However, it would seem worthy of further investigation when used in combination
      with other agents.

PMID- 12795688
TI  - The intraflagellar transport machinery of Chlamydomonas reinhardtii.
AB  - First discovered in the green alga, Chlamydomonas, intraflagellar transport (IFT)
      is the bidirectional movement of protein particles along the length of eukaryotic
      cilia and flagella. Composed of approximately 16 different proteins, IFT
      particles are moved out to the distal tip of the organelle by kinesin-II and are
      brought back to the cell body by cytoplasmic dynein 1b. Mutant analysis of the
      IFT motor and particle proteins using diverse organisms has revealed a conserved
      and essential role for IFT in the assembly and maintenance of cilia and flagella.
      IFT is thought to mediate this assembly through the delivery of axonemal
      precursors out to the distal tip of the growing organelle. Consistent with this
      model, the IFT particle proteins are rich in protein-protein binding motifs,
      suggesting that the particles may act as scaffolds for the binding of multiple
      cargoes. With most of the IFT proteins now identified at the level of the gene,
      this review will briefly examine both the structure and function of the IFT
      machinery of Chlamydomonas reinhardtii.

PMID- 12795689
TI  - Elucidation of basal body and centriole functions in Chlamydomonas reinhardtii.
AB  - In eukaryotic cells, basal bodies and their structural equivalents, centrioles,
      play essential roles. They are needed for the assembly of flagella or cilia as
      well as for cell division. Chlamydomonas reinhardtii provides an excellent model
      organism for the study of the basal body and centrioles. Genes for two new
      members of the tubulin superfamily are needed for basal body/centriole
      duplication. In addition, other genes that play roles in the duplication and
      segregation of basal bodies are discussed.

PMID- 12795690
TI  - Protein transport and signal transduction during fertilization in chlamydomonas.
AB  - Fertilization in Chlamydomonas begins with flagellar adhesion between mating type
      plus and mating type minus gametes and is consummated within minutes by zygote
      formation. Once fusion occurs, the newly merged gametes cease existence as
      distinct entities, and the diploid zygote immediately initiates transcription of
      zygote-specific genes. Accomplishing fertilization within such a short time
      requires the rapid and signaled movement of pre-existing membrane and cytoplasmic
      proteins between and within several cellular compartments. Generation within the
      adhering flagella of the initial signals for protein movement, as well as
      movement itself of at least one cytoplasmic protein from the cell body to the
      flagella, depend on the microtubule motor, kinesin-II and presumably on
      intraflagellar transport (IFT). Adhesion and fusion of the two gametes depend on
      a second translocation event, the movement of an adhesion/fusion protein onto the
      surface of a rapidly elongating, microvillous-like fusion organelle. Finally, the
      merging of the two separate gametes, each containing sex-specific proteins, into
      a single cell allows the formerly separate proteins to form new interactions that
      regulate zygote development. Two proteins - a nuclease and a homeodomain protein 
      which were present only in the plus gamete, are 'delivered' to the cytoplasm of
      the zygote during gamete fusion. The nuclease is selectively imported into the
      minus chloroplast, where it degrades the chloroplast DNA, thereby ensuring
      uniparental inheritance of plus chloroplast traits. The homeodomain protein binds
      with an as yet unidentified protein delivered by the minus gamete, and the new
      complex activates transcription of zygote-specific genes.

PMID- 12795691
TI  - Movement of plasma-membrane-associated clathrin spots along the microtubule
      cytoskeleton.
AB  - The current understanding of the role of plasma- membrane-associated clathrin
      suggests that clathrin-coated pits form at the sites of activated receptors and
      then, following internalization, the clathrin coat is rapidly shed. Utilizing
      total internal reflection fluorescence microscopy (TIR-FM), we have documented
      linear lateral motion of cell-surface-associated dsRed-clathrin spots parallel to
      the plasma membrane. Clathrin spot motility was observed in multiple cell lines
      (MDCK, CHO, Cos-7 and HeLa). In MDCK cells dsRed-clathrin spots moved along
      linear pathways up to 4 micro m in length with rates of approximately 0.8 micro
      m/s. Spots did not generally undergo internalization during movement. The motion
      of these puncta was coincident with the microtubule cytoskeleton, and
      depolymerization of microtubules reduced spot motility over 10-fold. Over
      expression of the microtubule-associated protein tau-EGFP decreased spot run
      length by 40% without affecting the rate of movement. Thus dsRed-clathrin puncta
      move along the microtubule cytoskeleton parallel to the cell surface.

PMID- 12795692
TI  - Endocytosis of synaptotagmin 1 is mediated by a novel, tryptophan-containing
      motif.
AB  - The rate at which a membrane protein is internalized from the plasma membrane can
      be regulated by revealing a latent internalization signal in response to an
      appropriate stimulus. Internalization of the synaptic vesicle membrane protein,
      synaptotagmin 1, is controlled by two distinct regions of its intracytoplasmic
      C2B domain, an internalization signal present in the 29 carboxyterminal (CT)
      amino acids and a separate regulatory region. We have now characterized the
      internalization motif by mutagenesis and found that it involves an essential
      tryptophan in the last beta strand of the C2B domain, a region that is distinct
      from the AP2-binding site previously described. Internalization through the
      tryptophan-based motif is sensitive to eps15 and dynamin mutants and is therefore
      likely to be clathrin mediated. A tryptophan-to-phenylalanine mutation had no
      effect on internalization of the CT domain alone, but completely inhibited
      endocytosis of the folded C2B domain. This result suggests that recognition of
      sorting motifs can be influenced by their structural context. We conclude that
      endocytosis of synaptotagmin 1 requires a novel type of internalization signal
      that is subject to regulation by the rest of the C2B domain.

PMID- 12795693
TI  - PtdIns(3,5)P2 is required for delivery of endocytic cargo into the multivesicular
      body.
AB  - The endocytic pathway transports cargo from the plasma membrane to early
      endosomes, where certain cargoes are sorted to the late endosome/multivesicular
      body. Biosynthetic cargo destined for the lysosome is also trafficked through the
      multivesicular body. Once delivered to the multivesicular body, cargo destined
      for the interior of the lysosome is selectively sorted into vesicles that bud
      into the lumen of the multivesicular body. These vesicles are released into the
      lumen of the lysosome upon the fusion of the multivesicular body and lysosomal
      limiting membranes. The yeast protein Fab1, which catalyzes the production of
      phosphatidylinositol (3,5) bisphosphate [PtdIns(3,5)P2], is necessary for proper
      sorting of biosynthetic cargo in the multivesicular body. Utilizing an
      endocytosis screen, we isolated a novel allele of FAB1 that contains a point
      mutation in the lipid kinase domain. Characterization of this allele revealed
      reduced PtdIns(3,5)P2 production, altered vacuole morphology, and biosynthetic
      protein sorting defects. We also found that endocytosis of the plasma membrane
      protein Ste3 is partially blocked downstream of the internalization step, and
      that delivery of the dye FM4-64 to the vacuole is delayed in fab1 mutants.
      Additionally, Ste3 is not efficiently sorted into multivesicular body vesicles in
      fab1 mutants and instead localizes to the vacuolar limiting membrane. These data
      show that PtdIns(3,5)P2 is necessary for proper trafficking and sorting of
      endocytic cargo through the late endosome/multivesicular body.

PMID- 12795694
TI  - Overexpression and mislocalization of a tail-anchored GFP redefines the identity
      of peroxisomal ER.
AB  - Peroxisomal ascorbate peroxidase (APX) sorts indirectly via a subdomain of the ER
      (peroxisomal ER) to the boundary membrane of peroxisomes in tobacco Bright Yellow
      2 cells. This novel subdomain characteristically appears as fluorescent
      reticular/circular compartments distributed variously in the cytoplasm. Further
      characterizations are presented herein. A peptide possessing the membrane
      targeting information for peroxisomal APX was fused to GFP (GFP-APX). Transiently
      expressed GFP-APX sorted to peroxisomes and to reticular/circular compartments;
      in both cases, the GFP moiety faced the cytosol. Of particular interest, both
      homotypic and heterotypic aggregates of peroxisomes, mitochondria, and/or
      plastids were formed. The latter two organelles comprised the circular portion of
      the reticular/circular compartments, apparently as a consequence of
      oligomerization (zippering) of the GFP moieties after insertion into the outer
      membranes of the affected organelles. These results, coupled with the
      accumulation of endogenous peroxisomal APX in cytoplasmic, noncircular
      compartment(s) following treatment with brefeldin A, indicate that authentic
      peroxisomal ER is composed only of a reticular compartment(s). Equally important,
      the data show that overexpressed, membrane-targeted GFP fusion proteins have a
      propensity to form organelle aggregates that may lead to misinterpretations of
      sorting pathways of trafficked proteins.

PMID- 12795696
TI  - Protein interaction analysis of SCF ubiquitin E3 ligase subunits from
      Arabidopsis.
AB  - Ubiquitin E3 ligases are a diverse family of protein complexes that mediate the
      ubiquitination and subsequent proteolytic turnover of proteins in a highly
      specific manner. Among the several classes of ubiquitin E3 ligases, the Skp1
      Cullin-F-box (SCF) class is generally comprised of three 'core' subunits: Skp1
      and Cullin, plus at least one F-box protein (FBP) subunit that imparts
      specificity for the ubiquitination of selected target proteins. Recent genetic
      and biochemical evidence in Arabidopsis thaliana suggests that post-translational
      turnover of proteins mediated by SCF complexes is important for the regulation of
      diverse developmental and environmental response pathways. In this report, we
      extend upon a previous annotation of the Arabidopsis Skp1-like (ASK) and FBP gene
      families to include the Cullin family of proteins. Analysis of the protein
      interaction profiles involving the products of all three gene families suggests a
      functional distinction between ASK proteins in that selected members of the
      protein family interact generally while others interact more specifically with
      members of the F-box protein family. Analysis of the interaction of Cullins with
      FBPs indicates that CUL1 and CUL2, but not CUL3A, persist as components of
      selected SCF complexes, suggesting some degree of functional specialization for
      these proteins. Yeast two-hybrid analyses also revealed binary protein
      interactions between selected members of the FBP family in Arabidopsis. These and
      related results are discussed in terms of their implications for subunit
      composition, stoichiometry and functional diversity of SCF complexes in
      Arabidopsis.

PMID- 12795697
TI  - Loss of actin cytoskeletal function and EDS1 activity, in combination, severely
      compromises non-host resistance in Arabidopsis against wheat powdery mildew.
AB  - Plant immunity against the majority of the microbial pathogens is conveyed by a
      phenomenon known as non-host resistance (NHR). This defence mechanism affords
      durable protection to plant species against given species of phytopathogens. We
      investigated the genetic basis of NHR in Arabidopsis against the wheat powdery
      mildew fungus Blumeria graminis f. sp. tritici (Bgt). Both primary and
      appressorial germ tubes were produced from individual Bgt conidia on the surface
      of the Arabidopsis leaves. Attempted infection occasionally resulted in
      successful penetration, which led to the development of an abnormal unilateral
      haustorium. Inoculation of a series of Arabidopsis defence-related mutants with
      Bgt resulted in the attenuation of reactive oxygen intermediate (ROI) production
      and salicylic acid (SA)-dependent defence gene expression in eds1, pad4 and nahG
      plants, which are known to be defective in some aspects of host resistance.
      Furthermore, Bgt often developed bilateral haustoria in the mutant Arabidopsis
      lines that closely resembled those formed in wheat. A similar decrease in NHR was
      observed following treatment of the wild-type Arabidopsis plants with
      cytochalasin E, an inhibitor of actin microfilament polymerisation. In eds1
      mutants, inhibition of actin polymerisation severely compromised NHR in
      Arabidopsis against Bgt. This permitted completion of the Bgt infection cycle on
      these plants. Therefore, actin cytoskeletal function and EDS1 activity, in
      combination, are major contributors to NHR in Arabidopsis against wheat powdery
      mildew.

PMID- 12795698
TI  - Tumour development in Arabidopsis thaliana involves the Shaker-like K+ channels
      AKT1 and AKT2/3.
AB  - After completion of the Arabidopsis genome-sequencing programme, crown galls
      induced by Agrobacterium tumefaciens may become a model system to study plant
      tumour development. The molecular mechanisms of nutrient supply to support tumour
      growth and development are still unknown. In this study, we have identified a
      unique profile of Shaker-like potassium channels in agrobacteria-induced
      Arabidopsis tumours. Comparing the gene expression pattern of rapidly growing
      tumours with that of non-infected tissues, we found the suppression of shoot in
      favour of root-specific K+ channels. Among these, the upregulation of AKT1 and
      AtKC1 and the suppression of AKT2/3 and GORK were most pronounced. As a
      consequence, K+ uptake and accumulation were elevated in the tumour (163 mm)
      compared to control tissues (92 mm). Patch clamp studies on tumour protoplasts
      identified a population expressing the electrical properties of the AKT1 K+
      channel. Furthermore, plants lacking a functional AKT1 or the AKT2/3 phloem K+
      channel gene did not support tumour growth. This indicates that the delivery of
      potassium by AKT1 and the direction of assimilates, triggered by AKT2/3, are
      essential for tumour growth.

PMID- 12795699
TI  - Sodium transport and HKT transporters: the rice model.
AB  - Na+ uptake in the roots of K+-starved seedlings of barley, rice, and wheat was
      found to exhibit fast rate, low Km, and high sensitivity to K+. Sunflower plants
      responded in a similar manner but the uptake was not K+ sensitive. Ba2+ inhibited
      Na+ uptake, but not K+ uptake in rice roots. This demonstrated that Na+ and K+
      uptake are mediated by different transporters, and that K+ blocked but was not
      transported by the Na+ transporter. The genome of rice cv. Nipponbare contains
      seven HKT genes, which may encode Na+ transporters, plus two HKT pseudogenes.
      Yeast expressions of OsHKT1 and OsHKT4 proved that they are Na+ transporters of
      high and low affinity, respectively, which are sensitive to K+ and Ba2+. Parallel
      experiments of K+ and Na+ uptake in yeast expressing the wheat or rice HKT1
      transporters proved that they were very different; TaHKT1 transported K+ and Na+,
      and OsHKT1 only Na+. Transcript expressions in shoots of the OsHKT genes were
      fairly constant and insensitive to changes in the K+ and Na+ concentrations of
      the nutrient solution. In roots, the expressions were much lower than in shoots,
      except for OsHKT4 and OsHKT1 in K+-starved plants. We propose that OsHKT
      transporters are involved in Na+ movements in rice, and that OsHKT1 specifically
      mediates Na+ uptake in rice roots when the plants are K+ deficient. The incidence
      of HKT ESTs in several plant species suggests that the rice model with many HKT
      genes applies to other plants.

PMID- 12795700
TI  - A pea antisense gene for the chloroplast stromal processing peptidase yields
      seedling lethals in Arabidopsis: survivors show defective GFP import in vivo.
AB  - The stromal processing peptidase (SPP) of chloroplasts is a metalloendopeptidase
      that cleaves in vitro a broad range of precursor substrates. Here, we have
      investigated SPP's role in vivo. Two pea cDNA antisense constructs encoding
      either full-length SPP (AS4.0) or its N-terminal half (AS2.2) are introduced into
      Arabidopsis, which contains one gene for SPP that codes for one isoform. Our
      analyses show that AS4.0 produces a strong mutant phenotype, with a large
      percentage of the plants dying as seedling lethals. Surviving plants exhibited
      slower shoot and root growth, and grossly aberrant leaf morphology. Green and
      white sectoring, and purple pigmentation was observed. In cells where
      chloroplasts could be identified, they were fewer in number by at least 40%,
      thylakoids were not fully developed, and starch granules accumulated. The
      phenotype produced by AS2.2 was less severe. Using green fluorescent protein
      (GFP) fused to a transit peptide as a reporter, we examined import into
      chloroplasts in vivo. In the Arabidopsis antisense lines, GFP was located
      primarily in the cytosol, indicating that an early step in the import pathway was
      impeded. In a tobacco AS14 line expressing AS2.2, GFP was located in the cytosol,
      on the envelope, and in the stroma. The three patterns were observed in different
      cells, suggesting that the import capacity of individual cells was not the same.
      Our in vivo studies demonstrate that SPP is essential for chloroplast biogenesis
      and plant survival. SPP does not act independently in the stroma, but its
      activity influences earlier steps in the import pathway.

PMID- 12795701
TI  - The GA octodinucleotide repeat binding factor BBR participates in the
      transcriptional regulation of the homeobox gene Bkn3.
AB  - In the dominant mutant Hooded (K), the barley gene BKn3 is overexpressed as a
      result of a duplication of 305 bp in intron IV. When fused to a cauliflower
      mosaic virus 35S minimal promoter, the 305 bp element activates gene expression
      in tobacco, as does a 655 bp BKn3 promoter sequence. Both DNA fragments contain a
      (GA)8 repeat (GA/TC)8. A one-hybrid screen using the 305 bp element as the DNA
      target led to the cloning of the barley b recombinant (BBR) protein, which binds
      specifically to the (GA/TC)8 repeat. BBR is nuclear targeted and is a
      characterized nuclear localization signal (NLS) sequence, a DNA-binding domain
      extended up to 90 aa at the C-terminus and a putative N-terminal activation
      domain. The corresponding gene has no introns and is ubiquitously expressed in
      barley tissues. In co-transfection experiments, BBR activates (GA/TC)8-containing
      promoters, and its overexpression in tobacco leads to a pronounced leaf shape
      modification. BBR has properties of a GAGA-binding factor, but the corresponding
      gene has no sequence homology to Trl and Psq of Drosophila, which encode
      functionally analogous proteins. In Arabidopsis, (GA/TC)8 repeats occur
      particularly within 1500 bp upstream of gene start codons included in some
      homeodomain genes of different classes. The data presented suggest that
      expression of the barley BKn3 is regulated, at least in part, by the binding of
      the transcription factor BBR to GA/TC repeats.

PMID- 12795702
TI  - HFR1, a putative bHLH transcription factor, mediates both phytochrome A and
      cryptochrome signalling.
AB  - Plants are very sensitive to their light environment. They use cryptochromes and
      phytochromes to scan the light spectrum. Those two families of photoreceptors
      mediate a number of similar physiological responses. The putative bHLH (basic
      Helix Loop Helix) transcription factor long hypocotyl in far-red (HFR1) is
      important for a subset of phytochrome A (phyA)-mediated light responses.
      Interestingly, hfr1 alleles also have reduced de-etiolation responses, including
      hypocotyl growth, cotyledon opening and anthocyanin accumulation, when grown in
      blue light. This phenotype is particularly apparent under high fluence rates. The
      analysis of double mutants between hfr1 and different blue light photoreceptor
      mutants demonstrates that, in addition to its role in phyA signalling, HFR1 is a
      component of cryptochrome 1 (cry1)-mediated light signalling. Moreover, HFR1 mRNA
      levels are high both in blue and in far-red light but low in red light. These
      results identify HFR1 as a positively acting component of cry1 signalling and
      indicate that HFR1 integrates light signals from both phyA and cry1.

PMID- 12795703
TI  - Suppression of fructokinase encoded by LeFRK2 in tomato stem inhibits growth and
      causes wilting of young leaves.
AB  - Fructokinases catalyze the key step of fructose phosphorylation in plants.
      LeFRK2, the major fructokinase-encoding gene in tomato plants, is abundantly
      expressed in roots, stems, and fruits. To analyze the role of LeFRK2 in plant
      development, we analyzed transgenic tomato plants with sense and antisense
      expression of StFRK, the potato homolog of LeFRK2. Increased fructokinase
      activity had no effect. However, plants in which LeFRK2 was specifically
      suppressed, either via antisense suppression or via co-suppression, exhibited
      growth inhibition and wilting of young leaves at daytime. Grafting experiments
      indicated that a stem interstock of antisense plants was sufficient to inhibit
      growth and cause leaf wilting. Stem secondary xylem exhibited particular
      suppression of LeFRK2 and the area of active xylem, estimated by eosin uptake,
      was significantly smaller in antisense stem compared to that of wild-type plants.
      These results suggest that LeFRK2 might be required for proper development of
      xylem that affected growth and wilting.

PMID- 12795704
TI  - Benzophenone synthase and chalcone synthase from Hypericum androsaemum cell
      cultures: cDNA cloning, functional expression, and site-directed mutagenesis of
      two polyketide synthases.
AB  - Benzophenone derivatives, such as polyprenylated benzoylphloroglucinols and
      xanthones, are biologically active secondary metabolites. The formation of their
      C13 skeleton is catalyzed by benzophenone synthase (BPS; EC 2.3.1.151) that has
      been cloned from cell cultures of Hypericum androsaemum. BPS is a novel member of
      the superfamily of plant polyketide synthases (PKSs), also termed type III PKSs,
      with 53-63% amino acid sequence identity. Heterologously expressed BPS was a
      homodimer with a subunit molecular mass of 42.8 kDa. Its preferred starter
      substrate was benzoyl-CoA that was stepwise condensed with three malonyl-CoAs to
      give 2,4,6-trihydroxybenzophenone. BPS did not accept activated cinnamic acids as
      starter molecules. In contrast, recombinant chalcone synthase (CHS; EC 2.3.1.74)
      from the same cell cultures preferentially used 4-coumaroyl-CoA and also
      converted CoA esters of benzoic acids. The enzyme shared 60.1% amino acid
      sequence identity with BPS. In a phylogenetic tree, the two PKSs occurred in
      different clusters. One cluster was formed by CHSs including the one from H.
      androsaemum. BPS grouped together with the PKSs that functionally differ from
      CHS. Site-directed mutagenesis of amino acids shaping the initiation/elongation
      cavity of CHS yielded a triple mutant (L263M/F265Y/S338G) that preferred benzoyl
      CoA over 4-coumaroyl-CoA.

PMID- 12795705
TI  - The Arabidopsis thaliana CUTA gene encodes an evolutionarily conserved copper
      binding chloroplast protein.
AB  - The Arabidopsis thaliana CUTA gene encodes a 182-amino-acid-long putative
      precursor of a chloroplast protein with high sequence similarity to
      evolutionarily conserved prokaryotic proteins implicated in copper tolerance.
      Northern analysis indicates that AtCUTA mRNA is expressed in all major tissue
      types. Analysis of cDNA clones and RT-PCR with total mRNA revealed alternative
      splicing of AtCUTA by retention of an intron. The intron-containing mRNA encodes
      a truncated 156-amino-acid protein as a result of stop codons in the included
      intron. The sequence of AtCutAp encoded by the fully spliced transcript suggests
      that the precursor consists of three domains: an N-terminal chloroplast transit
      sequence of 70 residues, followed by a domain with prokaryotic signal-sequence
      like characteristics and finally the most conserved C-terminal domain. The N
      terminal chloroplast transit sequence was functional to route a passenger protein
      into isolated pea chloroplasts with possible sorting to the envelope. Chloroplast
      localization was confirmed by Western blot analysis of isolated and fractionated
      chloroplasts. Recombinant AtCutA protein was expressed in Escherichia coli
      without the N-terminal 70-amino-acid chloroplast transit sequence. This
      recombinant AtCutAp was routed to the bacterial periplasm of E. coli. Purified
      recombinant AtCutAp is tetrameric and selectively binds Cu(II) ions with an
      affinity comparable to that reported for mammalian prion proteins.

PMID- 12795706
TI  - Monitoring expression profiles of Arabidopsis gene expression during rehydration
      process after dehydration using ca 7000 full-length cDNA microarray.
AB  - Plants respond and adapt to drought stress in order to survive under stress
      conditions. Several genes that respond to drought at the transcriptional level
      have been described, but there are few reports on genes involved in the recovery
      from dehydration. Analysis of rehydration-inducible genes should help not only to
      understand the molecular mechanisms of stress responses in higher plants, but
      also to improve the stress tolerance of crops by gene manipulation. We used a
      full-length cDNA microarray containing ca. 7000 Arabidopsis full-length cDNAs and
      identified 152 rehydration-inducible genes. Venn diagram analysis showed
      relationship of the rehydration-inducible genes to proline-inducible and water
      treatment-inducible genes. Among the 152 rehydration-inducible genes, 58 genes
      contained the ACTCAT sequence involved in proline- and hypoosmolarity-inducible
      gene expression in their promoter regions, suggesting that ACTCAT sequence is a
      major cis-acting element involved in rehydration-inducible gene expression, and
      that some novel cis-acting elements are involved in rehydration-inducible gene
      expression. Functional analysis of rehydration-inducible and rehydration
      repressed genes revealed their functions not only in the release from a stressed
      status but also in the recovery of growth in plants.

PMID- 12795707
TI  - Nerve regeneration and repair.

PMID- 12795710
TI  - Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic
      neuropathy.
AB  - OBJECTIVE: Our aims were to better understand the mechanisms underlying
      peripheral neuropathy with diabetes mellitus and to test the hypothesis that
      acute lowering of glucose levels induces apoptosis in hypoxic neurons. METHODS:
      We used rat dissociated dorsal root ganglion (DRG) neurons incubated in a medium
      high in glucose concentration (700 mg%) and room air (PO2 150 torr). After 5
      days, DRG neurons were placed in hypoxic conditions (PO2 7.6 torr) with a normal
      glucose (100 mg%) or high-glucose (700 mg%) medium containing 3 or 100 ng/mL of
      nerve growth factor. Acute lowering of glucose levels under hypoxic conditions
      led to apoptosis of DRG neurons. Apoptosis was demonstrated by bis-benzimide
      staining for nuclear fragmentation, electron microscopy, DNA laddering, and TUNEL
      staining. Caspase 3 immunocytochemistry and inhibition of neuronal death by the
      caspase inhibitor z-VAD-fmk (100 microM) confirmed that death was apoptotic.
      RESULTS: Hypoxia-induced death was decreased when DRG neurons were maintained in
      high-glucose medium, suggesting that high levels of substrate protected against
      hypoxia. Apoptosis was completely prevented by increasing the concentration of
      nerve growth factor from 3 to 100 ng/mL and was partially prevented by the
      addition of the antioxidant alpha-lipoic acid (500 microM). CONCLUSIONS: This
      model provides a novel means for studying the pathogenesis and treatment of early
      stages of diabetic neuropathy.

PMID- 12795711
TI  - Influence of testosterone on the electrical properties of scrotal nerves at the
      cutaneous and spinal levels in the male rat.
AB  - The scrotal nerves in the rat were studied electrophysiologically to describe
      their topographic organization in the skin and in the dorsal roots, and to
      determine if the electrical properties of these afferents are under the influence
      of testosterone. There are 2 afferent nerve branches innervating this area, the
      proximal scrotal branch supplying the proximal half of the scrotum (PSb), and the
      distal scrotal branch supplying the distal half (DSb). Results showed that
      afferent axons from PSb enter the spinal cord through the L5 and L6 dorsal roots,
      and axons from DSb enter the cord through the L6 and S1 dorsal roots. Mechanical
      stimulation of the scrotal skin exposed 3 dermatome areas, the L5, L6, and S1,
      with L6 being the longest dermatome with intermingled terminals from PSb and DSb.
      Decreased levels of testosterone after castration increased the threshold to
      trigger the activity of scrotal afferents, and the exogenous administration of
      the hormone reverted it. This effect was similar in the dorsal penile nerve. The
      decrease in androgen levels produced a reduction in the skin sensory field to
      mechanical stimuli that was restored after the administration of the hormone. As
      the scrotal nerves are highly stimulated during copulation in parallel with the
      dorsal penile nerve, it is suggested that the sensory field of the scrotal skin
      could be closely related to the modifications in sexual behavior after
      testosterone manipulation.

PMID- 12795712
TI  - The relation of clinical symptoms and anti-ganglioside antibodies to MEPPs
      frequency increase in 8 cases of variant type Guillain-Barre syndrome.
AB  - Many patients with variant forms of Guillain-Barre syndrome (vGBS) associated
      with anti-ganglioside antibodies, including Miller Fisher syndrome (MFS),
      sometimes exhibit miniature endplate potential (MEPP) frequency increases (MFI,
      described as alpha-latrotoxin-like effects in a previous report) and the factor
      to produce this effect is present in their sera. MFI-positive sera increase the
      frequency of MEPPs, then block neuromuscular transmission at the mouse
      neuromuscular junction. A connection between this effect at the neuromuscular
      junction and some vGBS symptoms is suspected. We measured MFI directly at several
      points during the clinical course of 8 vGBS patients who had various symptoms and
      courses. Six patients had confirmed MFI and this activity decreased with
      convalescence. In 3 clinically mild cases, we were able to elicit MFI using
      normal serum to supply complement after exposure to the patient's serum. The anti
      GQ1b/GT1a IgG titer, the extent of ophthalmoplegia and the extent of MFI were
      significantly correlated. They did not correlate with the severity of limb
      weakness or the occurrence of respiratory failure. These results support the
      hypothesis that MFI caused by anti-ganglioside antibodies is the pathogenic
      mechanism responsible for ophthalmoplegia in vGBS; different mechanisms or
      antibodies may explain limb weakness and respiratory failure. Furthermore, MFI
      may be an important indicator of how serum injures the nerve terminals. The
      symptoms of vGBS may result from multiple pathogenic factors.

PMID- 12795713
TI  - Antibodies to myelin-associated glycoprotein accelerate preferential motor
      reinnervation.
AB  - Predegeneration of nerve enhances its ability to support axon regeneration.
      Trophic factors are upregulated by reactive Schwann cells while potentially
      inhibitory molecules are removed. These experiments isolate the effects of one
      such inhibitory molecule, the myelin-associated glycoprotein (MAG), to determine
      its role in modifying regeneration after nerve repair. Suture of the mouse
      femoral nerve was followed by daily intraperitoneal injection of antibodies to
      MAG, antibodies to HNK-1, a specific muscle pathway marker, or no further
      treatment. Regeneration was assayed by double-labeling the femoral cutaneous and
      muscle branches with horseradish peroxidase and fluoro-gold after 4 weeks or 6
      weeks of regeneration. Four weeks after nerve repair, selective reinnervation of
      the muscle branch by motoneurons, or preferential motor reinnervation (PMR), was
      not seen in either controls or L2-antibody-treated animals. In contrast,
      treatment with MAG antibodies resulted in dramatic PMR. By 6 weeks, the controls
      had achieved borderline specificity, substantial PMR developed in the L2 antibody
      group and the MAG group changed little. Blocking access to MAG in the distal
      nerve stump thus accelerated and enhanced PMR. Sensory regeneration was depressed
      by both antibody treatments at 4 weeks but recovered by 6 weeks. Antibody
      administration has a generalized effect on sensory regeneration that is unrelated
      to the behavior of motoneurons in the same nerve.

PMID- 12795714
TI  - Microvasculitic paraproteinaemic polyneuropathy and B-cell lymphoma.
AB  - Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic
      neuropathies than is generally recognised, producing tissue destruction by
      convergent immune and physical mechanisms. We present a patient with a clinical
      syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in
      whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma.
      Microvasculitic changes were present in the first nerve biopsy, and the second
      showed extensive destruction of neural architecture and deposition of IgM-related
      material. A 2-stage pathogenic cascade is postulated and explored with a review
      of the relevant literature.

PMID- 12795715
TI  - Nerve compound action current (NCAC) measurements and morphometric analysis in
      the proximal segment after nerve transection and repair in a rabbit model.
AB  - In the evaluation of nerve regeneration using magneto-neurography (MNG), the
      proximal segment showed a reproducible decrease in peak-peak amplitude of the
      nerve compound action current's (NCAC) of 60%. To explain these changes,
      morphometry of myelinated axons in the proximal segment is compared to the MNG
      signals. A standardised nerve transection and reconstruction was performed in
      rabbits. NCACs were measured approximately 5 cm proximal to the lesion from
      operated and control nerves after 12 weeks. Histological samples were taken from
      the same area of the nerve where the NCACs were obtained. Results showed a
      decrease of the peak-peak amplitude of the NCAC of 57% compared to the control.
      Conduction velocity decreased 15% (not significant). Morphometry elicited a
      decrease in larger (10-15 microm) axons (284 +/- 134 vs 82 +/- 55) and an
      increase in smaller (2-5 microm) axons (1445 +/- 360 vs 1921 +/- 393). A strong
      correlation existed between the decrease in amplitude and the decrease in larger
      axons (0.85). Peak-peak amplitude varies approximately with the square of the
      diameter axon. Therefore, because peak-peak amplitude is mainly dependent on the
      larger-diameter axons, the decrease in peak-peak amplitude of the NCACs may be
      explained by a decrease in numbers of 10-15-microm axons.

PMID- 12795716
TI  - Evidence for impaired axonal regeneration in PMP22 duplication: studies in nerve
      xenografts.
AB  - Whether axonal regeneration in Charcot-Marie-Tooth (CMT) neuropathies is impaired
      has not been addressed in detail. Our studies in nude mice harboring xenografts
      from patients with different primary Schwann cell (SC) genetic defects suggested
      an intimate association between the onset of myelination and impairment in the
      growth capacity of nude mice axons engulfed by the mutant SCs. To assess the
      effects of peripheral myelin protein 22 (PMP22) gene duplication on the
      regeneration process, we conducted morphometric studies to generate temporal
      growth profiles of myelinated axons within the xenografts obtained from CMT1A
      patients and from healthy controls. Axon size distribution histograms in controls
      at different time intervals revealed that size differentiation of myelinated
      fibers within the grafts is established as early as 2 weeks, and that the
      temporal pattern of myelination of different sized axons has striking
      similarities to myelination during development. In PMP22 duplication grafts, the
      onset of myelination is delayed and the regeneration capacity of all fiber sizes
      is impaired. This defect, however, is most pronounced for the large diameter
      axons. In addition, significant large fiber loss occurred after 12 weeks with a
      concomitant new cycle of regeneration of small size axons. These studies show
      that the PMP22 duplication in SCs have profound effects on the regeneration
      process, which might be a contributing factor to preferential distal axonal loss.

PMID- 12795729
TI  - Patient choice. A randomized controlled trial of provider selection.
AB  - OBJECTIVE: To evaluate the impact of an intervention designed to help patients
      choose a new primary care provider (PCP) compared with the usual method of
      assigning patients to a new PCP. DESIGN: Randomized controlled trial conducted
      between November 1998 and June 2000. INTERVENTION: Provision of telephone or web
      based provider-specific information to aid in the selection of a provider.
      SETTING: Medical center within a large HMO. PATIENTS: One thousand and ninety
      patients who were >/=30 years old, whose previous PCP had retired and who
      responded to a mailed questionnaire 1 year after linkage with a new PCP.
      MEASUREMENTS AND MAIN RESULTS: The questionnaire assessed perceptions of choice,
      satisfaction, trust, and retention of the PCP. During the intervention period,
      85% of subjects obtained a new PCP. Intervention subjects were more likely to
      perceive that they chose their PCP (78% vs 22%; P <.001), to retain their PCP at
      1 year (93% vs 69%; P <.001), and to report greater overall satisfaction with the
      PCP (67% vs 57%; P <.01), compared to control subjects who were assigned to a
      PCP. The intervention subjects also reported greater trust in their PCP on most
      measures, but these differences did not remain statistically significant after
      adjustments for patient age, gender, ethnicity, education, and health status.
      CONCLUSIONS: Encouraging patients to choose their PCP can result in mutually
      beneficial outcomes for both patients and providers, such as greater overall
      satisfaction and duration of the relationship. Further research is needed to
      identify the types of information most useful in making this choice and to
      understand the relevant underlying patient expectations.

PMID- 12795730
TI  - Optimizing antibiotic prescribing for acute respiratory tract infections in an
      urban urgent care clinic.
AB  - OBJECTIVE: To decrease unnecessary antibiotic use for acute respiratory tract
      infections in adults in a point-of-service health care setting. DESIGN:
      Prospective, nonrandomized controlled trial. SETTING: An urban urgent care clinic
      associated with the major indigent care hospital in Denver, Colorado between
      October 2000 and April 2001. PATIENTS/PARTICIPANTS: Adults diagnosed with acute
      respiratory tract infections (bronchitis, sinusitis, pharyngitis, and nonspecific
      upper respiratory infection). A total of 554 adults were included in the baseline
      period (October to December 2000) and 964 adults were included in the study
      period (January to April 2001). INTERVENTIONS: A provider educational session on
      recommendations for appropriate antibiotic use recently published by the Centers
      for Disease Control and Prevention, and placement of examination room posters
      were performed during the last week of December 2000. Study period patients who
      completed a brief, interactive computerized education (ICE) module were
      classified as being exposed to the full intervention, whereas study period
      patients who did not complete the ICE module were classified as being exposed to
      the limited intervention. MEASUREMENTS AND MAIN RESULTS: The proportion of
      patients diagnosed with acute bronchitis who received antibiotics decreased from
      58% during the baseline period to 30% and 24% among patients exposed to the
      limited and full intervention, respectively (P <.001 for intervention groups vs
      baseline). Antibiotic prescriptions for nonspecific upper respiratory tract
      infections decreased from 14% to 3% and 1% in the limited- and full-intervention
      groups, respectively (P <.001 for intervention groups vs baseline). CONCLUSION:
      Antibiotic use for adults diagnosed with acute respiratory tract infections can
      be reduced in a point-of-service health care setting using a combination of
      patient and provider educational interventions.

PMID- 12795731
TI  - Communication patterns of primary care physicians in the United States and the
      Netherlands.
AB  - BACKGROUND: While international comparisons of medical practice have noted
      differences in length of visit, few studies have addressed the dynamics of visit
      exchange. OBJECTIVES: To compare the communication of Dutch and U.S. hypertensive
      patients and their physicians in routine medical visits. DESIGN: Secondary
      analysis of visit audio/video tapes contrasting a Dutch sample of 102 visits with
      27 general practitioners and a U.S. sample of 98 visits with 52 primary care
      physicians. MEASUREMENTS: The Roter Interaction Analysis System applied to visit
      audiotapes. Total visit length and duration of the physical exam were measured
      directly. MAIN RESULTS: U.S. visits were 6 minutes longer than comparable Dutch
      visits (15.4 vs 9.5 min, respectively), but the proportion of visits devoted to
      the physical examination was the same (24%). American doctors asked more
      questions and provided more information of both a biomedical and psychosocial
      nature, but were less patient-centered in their visit communication than were
      Dutch physicians. Cluster analysis revealed similar proportions of exam-centered
      (with especially long physical exam segments) and biopsychosocial visits in the 2
      countries; however, 48% of the U.S. visits were biomedically intensive, while
      only 18% of the Dutch visits were of this type. Fifty percent of the Dutch visits
      were socioemotional, while this was true for only 10% of the U.S. visits.
      CONCLUSIONS: U.S. and Dutch primary care visits showed substantial differences in
      communication patterns and visit length. These differences may reflect country
      distinctions in medical training and philosophy, health care system
      characteristics, and cultural values and expectations relevant to the delivery
      and receipt of medical services.

PMID- 12795732
TI  - Changes in the use of do-not-resuscitate orders after implementation of the
      Patient Self-Determination Act.
AB  - OBJECTIVE: To determine changes in the use of do-not-resuscitate (DNR) orders and
      mortality rates following a DNR order after the Patient Self-determination Act
      (PSDA) was implemented in December 1991. DESIGN: Time-series. SETTING: Twenty
      nine hospitals in Northeast Ohio. PATIENTS/PARTICIPANTS: Medicare patients (N =
      91,539) hospitalized with myocardial infarction, heart failure, gastrointestinal
      hemorrhage, chronic obstructive pulmonary disease, pneumonia, or stroke.
      MEASUREMENTS AND MAIN RESULTS: The use of "early" (first 2 hospital days) and
      "late" DNR orders was determined from chart abstractions. Deaths within 30 days
      after a DNR order were identified from Medicare Provider Analysis and Review
      files. Risk-adjusted rates of early DNR orders increased by 34% to 66% between
      1991 and 1992 for 4 of the 6 conditions and then remained flat or declined
      slightly between 1992 and 1997. Use of late DNR orders declined by 29% to 53% for
      4 of the 6 conditions between 1991 and 1997. Risk-adjusted mortality during the
      30 days after a DNR order was written did not change between 1991 and 1997 for 5
      conditions, but risk-adjusted mortality increased by 21% and 25% for stroke
      patients with early DNR and late DNR orders, respectively. CONCLUSIONS: Overall
      use of DNR orders changed relatively little after passage of the PSDA, because
      the increase in the use of early DNR orders between 1991 and 1992 was
      counteracted by decreasing use of late DNR orders. Risk-adjusted mortality rates
      after a DNR order generally remained stable, suggesting that there were no
      dramatic changes in quality of care or aggressiveness of care for patients with
      DNR orders. However, the increasing mortality for stroke patients warrants
      further examination.

PMID- 12795733
TI  - Physician perspectives on the importance of facts men ought to know about
      prostate-specific antigen testing.
AB  - OBJECTIVE: To determine physicians' rating of the importance of key facts men
      ought to know about prostate-specific antigen (PSA) screening and whether there
      are differences by specialty. PARTICIPANTS: A nationwide random sample of
      internists, family physicians, and urologists stratified by physician specialty
      from The Official ABMS Directory of Board-Certified Medical Specialists 2000
      Edition. MEASUREMENTS: Internists (N = 139), family physicians (N = 160), and
      urologists (N = 151) were asked to rate how important it is for men to know 17
      facts about PSA screening using a 5-point Likert scale. MAIN RESULTS: Of 769
      eligible physicians, 450 responded, for an overall response rate of 59%.
      Urologists and nonurologists differed in rating how important it was for men to
      know 9 of the 17 key facts. Eight of the nine statements that urologists and
      nonurologists disagreed upon concerned facts reflecting uncertainty.
      Nonurologists were more likely than urologists to rate facts reflecting
      uncertainty as highly important for men to know. These included statements about
      prostate cancer risk, screening with PSA, and treatment. CONCLUSIONS: Despite
      professional guidelines supporting informed decision making, the importance of
      facts men ought to know about PSA testing differ by physician specialty.
      Systematic differences may reflect differences in professional guidelines about
      PSA testing.

PMID- 12795734
TI  - Physician and patient factors associated with ordering a colon evaluation after a
      positive fecal occult blood test.
AB  - OBJECTIVE: Successful colorectal cancer screening relies in part on physicians
      ordering a complete diagnostic evaluation of the colon (CDE) with colonoscopy or
      barium enema plus sigmoidoscopy after a positive screening fecal occult blood
      test (FOBT). DESIGN: We surveyed primary care physicians about colorectal cancer
      screening practices, beliefs, and intentions. At least 1 physician responded in
      318 of 413 (77%) primary care practices that were affiliated with a managed care
      organization offering a mailed FOBT program for patients aged >/=50 years. Of
      these 318 practices, 212 (67%) had 602 FOBT+ patients from August through
      November 1998. We studied 184 (87%) of these 212 practices with 490 FOBT+
      patients after excluding those judged ineligible for a CDE or without demographic
      data. Three months after notification of the FOBT+ result, physicians were asked
      on audit forms if they had ordered CDEs for study patients. Patient- and
      physician-predictors of ordering CDEs were identified using logistic regression.
      MEASUREMENTS AND MAIN RESULTS: A CDE was ordered for only 69.5% of 490 FOBT+
      patients. After adjustment, women were less likely to have had CDE initiated than
      men (adjusted odds, 0.66; confidence interval, 0.44 to 0.97). Physician survey
      responses indicating intermediate or high intention to evaluate a FOBT+ patient
      with a CDE were associated with nearly 2-fold greater adjusted odds of actually
      initiating a CDE in this circumstance versus physicians with a low intention.
      CONCLUSIONS: Primary care physicians often fail to order CDE for FOBT+ patients.
      A CDE was less likely to be ordered for women and was influenced by physician's
      beliefs about CDEs.

PMID- 12795735
TI  - Improving patient satisfaction with the transfer of care. A randomized controlled
      trial.
AB  - OBJECTIVE: To determine whether educational sessions with medical residents, with
      or without letters to their patients, improve patient satisfaction with transfer
      of their care from a departing to a new resident in an internal medicine clinic.
      DESIGN: Observational study in Year 1 to establish a historical control, with a
      randomized intervention in Year 2. SETTING: An internal medicine clinic in a
      teaching hospital. PATIENTS/PARTICIPANTS: Patients of departing residents
      completed questionnaires in the waiting room at their first visit with a new
      resident, with mail-administered questionnaires for patients not presenting to
      the clinic within 3 months after transfer of their care. In Year 1, 376 patients
      completed questionnaires without intervention. The following spring, we conducted
      interactive seminars with 12 senior residents to improve their transfer of care
      skills (first intervention). Half of their patients were then randomized to
      receive a letter from the new doctor informing them of the change (second
      intervention). We assessed the efficacy of the interventions by administering
      questionnaires to 437 patients in the months following the interventions.
      MEASUREMENTS AND MAIN RESULTS: Multivariate analysis of Year 1 results identified
      doctors personally informing patients prior to leaving as the single strongest
      predictor of patient satisfaction (partial R2=.41). In Year 2, our first
      intervention increased the percentage of patients informed by their doctors from
      71% in 1991 to 79% in 1992 (P <.001). Mean satisfaction dramatically improved,
      with the fraction of fully satisfied patients increasing from 47% at baseline, to
      61% with the first intervention alone, and 72% with both interventions (P
      <.0001). CONCLUSIONS: Simple methods such as resident education and direct
      mailings to patients significantly ease the difficult process of transferring
      patients from one physician to another. This has implications not only for
      residency programs, but for managed care networks competing to attract and retain
      patients.

PMID- 12795736
TI  - Educational innovations in academic medicine and environmental trends.
AB  - Fifteen educational innovations in academic medicine are described in relation to
      5 environmental trends. The first trend, demands for increased clinical
      productivity, has diminished the learning environment, necessitating new
      organizational structures to support teaching, such as academies of medical
      educators, mission-based management, and faculty development. The second trend is
      multidisciplinary approaches to science and education. This is stimulating the
      growth of multidisciplinary curricular design and oversight along with integrated
      curricular structures. Third, the science of learning advocates the use of case
      based, active learning methods; learning communities such as societies and
      colleges; and instructional technology. Fourth, shifting views of health and
      disease are encouraging the addition of new content in the curriculum. In
      response, theme committees are weaving content across the curriculum, new courses
      are being inserted into curricula, and community-based education is providing
      learning experiences outside of academic medical centers. Fifth, calls for
      accountability are leading to new forms of performance assessment using objective
      structured clinical exams, clinical examination exercises, simulators, and
      comprehensive assessment programs. These innovations are transforming medical
      education.

PMID- 12795738
TI  - Physicians' use of and attitudes toward electronic mail for patient
      communication.
AB  - To assess physicians' use of and attitudes toward electronic mail (e-mail) for
      patient communication, we conducted a mail-in survey of physicians who see
      patients in outpatient clinics affiliated with a large academic medical center (N
      = 283). Seventy-two percent of physicians reported using e-mail to communicate
      with patients, averaging 7.7 e-mails from patients per month. The lowest level of
      use was by community-based primary care physicians (odds ratio, 0.22; 95%
      confidence interval, 0.08 to 0.59). Those physicians who reported using e-mail
      with patients reported high satisfaction with its use. Although physicians were
      concerned about the confidentiality of e-mail, few discussed this issue with
      patients.

PMID- 12795737
TI  - Utilization of papanicolaou smears by South Asian women living in the United
      States.
AB  - OBJECTIVES: Papanicolaou (Pap) smears are an underutilized screening modality
      among racial and ethnic minorities. However, no data exist on Pap smear
      utilization among South Asians, a rapidly growing population in the United
      States, whose country of origin includes India, Pakistan, Bangladesh, and Sri
      Lanka. We determined rates and identified variables associated with Pap smear
      receipt by South Asians. DESIGN: A self-administered survey instrument was mailed
      to a random sample of South Asians nationwide over a 3-month time period. South
      Asian households were identified by surnames that were used to search white pages
      in telephone directories, Department of Motor Vehicle records, and voter
      registries. Questions regarding Pap smear receipt were taken from the 1999
      National Health Interview Survey. Sociodemographic information and measures of
      acculturation were obtained. PARTICIPANTS: A nationwide nonprobability sample of
      South Asian women. INTERVENTION: Cross-sectional observational study.
      MEASUREMENTS AND MAIN RESULTS: The overall response rate was 42%. In this sample,
      South Asians belonged to a high socioeconomic strata (SES), with 45% having a
      household income of >$80,000 and 42% having a master's degree. Three quarters of
      the respondents (73%) reported having a Pap smear in the last 3 years. In
      multivariate logistic regression analysis, South Asian women had greater odds of
      having had a Pap smear if they were married (P <.001), more educated (P =.004),
      had a usual source of care (P =.002), and were more acculturated (P =.004).
      CONCLUSIONS: Despite the high SES of South Asian women, their rates of Pap smear
      receipt were lower than national recommendations. Marital status, socioeconomic
      status, and acculturation are all associated with Pap smear receipt. South Asian
      communities should be targeted for outreach to promote Pap smear utilization.

PMID- 12795740
TI  - Patient-provider communication in cancer screening.

PMID- 12795739
TI  - Measures of health-related quality of life for adults with acute sinusitis. A
      systematic review.
AB  - CONTEXT: Symptoms suggestive of acute sinusitis are a common reason for patients
      to visit primary care providers. Since objective measures of outcome have not
      been shown to be related to patient reported outcomes, measures of treatment
      success have focused on symptom relief and improved health-related quality of
      life (HRQL). Assessing the appropriate role of treatment - for example,
      antibiotics for patients with acute sinusitis - requires valid, reliable, and
      responsive measures of outcome. We identified symptom scores and HRQL instruments
      for adults with sinusitis and assessed their performance characteristics. DATA
      SOURCES: Articles identified through computer searches of the medline,
      premedline, and embase databases, the Cochrane Library, and internet documents;
      inquiries to experts in sinusitis and outcomes assessment; and review of
      reference lists. STUDY SELECTION: Studies that used HRQL instruments or evaluated
      the performance characteristics of symptom scores in adults with sinusitis,
      published in English after 1966. DATA EXTRACTION: Two reviewers independently
      extracted data on study design, setting, and patient characteristics; instrument
      length and format; and instrument validity, reliability, responsiveness to
      change, and interpretability. Study quality was assessed using a 10-point score.
      DATA SYNTHESIS: Of 1,340 articles in the original search, 29 articles using 16
      HRQL instruments and 5 symptoms scores met inclusion and exclusion criteria. The
      overall quality of these studies was low; only 4 studies scored higher than 4 of
      10 points. Four studies included patients with acute sinusitis, but only 2
      included exclusively acute sinusitis patients. Three instruments have been shown
      to meet basic requirements for validity, reliability, and responsiveness: the
      Chronic Sinusitis Survey, the Rhinosinusitis Outcome Measure-31, and the
      Sinonasal Outcome Test-16. No instrument has been validated in a primary care
      setting or for patients with acute sinusitis. CONCLUSIONS: Few validated measures
      of sinusitis-specific HRQL are available. The 3 instruments shown to be valid,
      reliable, and responsive have been assessed in patients with chronic sinusitis.
      No measure has been validated in primary care settings or for patients with acute
      sinusitis. A lack of valid, responsive outcome measures may limit current
      treatment recommendations for patients with acute sinusitis.

PMID- 12795741
TI  - Virtual physicians, health systems, and the healing relationship.

PMID- 12795742
TI  - Whither medical education in the United States?

PMID- 12795744
TI  - TRAILing gastrointestinal pathogenesis.

PMID- 12795745
TI  - Emerging role of calprotectin in gastroenterology.
AB  - Calprotectin is a calcium and zinc binding protein of the S100 family derived
      predominantly from neutrophils and monocytes. It is detectable in body fluids and
      tissue samples and is emerging as a valuable marker in the diagnosis, and the
      monitoring and determining of the prognosis of commonly encountered
      gastroenterological conditions. Fecal calprotectin, in particular, has for a long
      time been regarded as a promising marker of gastrointestinal pathology and has
      now been established as a routine test in Norway and at several centers in the
      UK.

PMID- 12795746
TI  - Flow cytometric measurement of tumor necrosis factor-related apoptosis-inducing
      ligand and its receptors in gastric epithelium and infiltrating mucosal
      lymphocytes in Helicobacter pylori-associated gastritis.
AB  - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and
      its receptors have recently been reported to be responsible for apoptotic
      signaling molecules. However, little is known about TRAIL-mediated apoptosis in
      the human glandular stomach. METHODS: Biopsies from 66 patients (28 Helicobacter
      pylori-negative, 38 H. pylori-positive) were investigated for phenotypic
      distribution of TRAIL and its receptors DR4/DR5 and DcR2 on mucosal epithelium,
      and infiltrating mucosal lymphocytes using flow cytometry. Apoptosis of the cells
      was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick
      and labeling (TUNEL). In addition, the phenotypic distribution of CD antigens on
      infiltrating major T- and B-lymphocytes were determined. RESULTS: Membrane-bound
      TRAIL and its receptors were constitutively expressed in all patients with high
      levels in the gastric mucosal epithelium. In particular, these protein molecules
      were overexpressed in mucosal lymphocytes coupled with increased proportions of
      CD19+ B cells, and CD3+ T cells bearing CD8+CD11b- and CD4+CD62L- surface
      phenotypes in H. pylori-positive gastric mucosa. The frequencies of apoptotic
      epithelium and infiltrating lymphocytes in H. pylori-associated gastritis were
      significantly greater than those of H. pylori-negative normal mucosa (P < 0.01).
      CONCLUSION: The present findings show that flow cytometric analysis is useful for
      detection of membrane-bound TRAIL and its receptors in gastric epithelium and
      infiltrating mucosal lymphocytes.

PMID- 12795747
TI  - Pulse-wave velocity and cardiovascular risk factors in subjects with Helicobacter
      pylori infection.
AB  - BACKGROUND: Helicobacter pylori infection has been reported to correlate with the
      onset of cardiovascular diseases. However, the relationship between H. pylori
      infection and the development of arteriosclerosis has not been fully
      investigated. We performed a cross-sectional study to clarify the possible role
      of H. pylori infection in the development of arteriosclerosis. METHODS: The
      subjects were 996 cases who attended their annual medical check-up between April
      and August 2001. H. pylori infection status was determined by assaying serum anti
      H. pylori immunoglobulin G antibodies. Total cholesterol, high-density
      lipoprotein cholesterol (HDLC), triglyceride, fasting blood glucose, hemoglobin
      A1c and leukocyte levels were determined. Arteriosclerotic parameters (systolic
      blood pressure (SBP), ankle brachial index (ABI) and pulse-wave velocity (PWV))
      were measured non-invasively using an automatic device. The data for H. pylori
      seropositive and -seronegative individuals were compared. RESULTS: Five hundred
      and seventy-three subjects (57.5%) were H. pylori-seropositive. After adjustment
      for sex, age, body mass index, and smoking and drinking habits, the HDLC levels
      of the seropositive and seronegative groups differed markedly (55.0 vs 58.0
      mg/dL, P < 0.0001). Although there were no differences between the overall
      adjusted SBP and ABI values, the PWV was higher in H. pylori-seropositive than 
      seronegative young (<39 years old) individuals (heart-carotid PWV: 632.2 vs 589.7
      cm/s, P = 0.027). These differences tended to disappear with aging. CONCLUSIONS:
      The degree of arterial stiffness in H. pylori-positive young subjects is higher
      than that in H. pylori-negative young subjects. However, no difference between
      the arterial stiffness values of H. pylori-seropositive and -seronegative elderly
      individuals was observed.

PMID- 12795748
TI  - Effect of different doses of furazolidone with amoxicillin and omeprazole on
      eradication of Helicobacter pylori.
AB  - BACKGROUND: Resistance to metronidazole is one of the most common reasons for
      Helicobacter pylori treatment failure with classic triple therapy. In contrast,
      the clarithromycin-based regimen is not cost-effective for developing countries.
      Furazolidone is a very good substitute for metronidazole and clarithromycin, but
      its many side-effects limit widespread use. The aim of the present study was to
      assess the efficacy of two different doses of furazolidone in combination with
      amoxycillin and omeprazole. METHODS: A total of 123 patients with duodenal ulcer
      were randomized and received the following medications for two weeks. Group A:
      furazolidone 2 x 200 mg + amoxycillin 2 x 1 g + omeprazole 2 x 20 mg/day. Group
      B: furazolidone 2 x 50 mg + amoxycillin 2 x 1 g + omeprazole 2 x 20 mg/day.
      Control endoscopy was performed after 6 weeks and two biopsy specimens from the
      antrum and two from the corpus were taken for a urease test and histology.
      Eradication was concluded if all tests were negative for H. pylori. RESULTS: In
      total, 110 patients completed the study. Four patients in group A did not
      tolerate the regimen on day 8 of therapy and were excluded from the study.
      Serious complications such as fever, and fatigue and dizziness, which occurred in
      the beginning of the second week of treatment (days 8-10), were more common in
      group A than in group B (19%, 15.9% and 14.3%, respectively, in group A vs 0% in
      group B). The eradication rate by per protocol analysis was significantly higher
      in group A than in group B (88.9%vs 67.9%, respectively, P = 0.008). However,
      this difference was low and not statistically significant by intention-to-treat
      analysis (76.2% in group A and 62.3% in group B, P = 0.09). CONCLUSION: The
      regimen with a non-reduced dose of furazolidone in combination with amoxycillin
      and omeprazole was effective when the patients tolerated the drugs and completed
      the study.

PMID- 12795749
TI  - Rabeprazole in a one-week eradication therapy of Helicobacter pylori: comparison
      of different dosages.
AB  - AIM: Many data regarding omeprazole-, lanzoprazole- and pantoprazole-based triple
      therapy for Helicobacter pylori (H. pylori) eradication have been reported, but
      there is few data present regarding rabeprazole (R). We report the efficacy and
      tolerability of rabeprazole in different dosages in association with
      clarithromycin (C)and tinidazole (T) in H. pylori eradication. DESIGN AND
      METHODS: Ninety-four H. pylori-positive patients with dyspeptic symptoms were
      enrolled and randomly allocated to eradication therapy in two different one-week
      regimens. In regimen A, 47 patients received R 20 mg b.i.d, C 500 mg b.i.d and T
      500 mg b.i.d, while in regimen B, 47 patients received R 10 mg b.i.d, C 500 mg
      b.i.d and T 500 mg b.i.d. Eradication of H. pylori was evaluated by a 13C urea
      breath test (UBT) two months after the end of the therapy. RESULTS: Four patients
      (two in each regimen) did not complete treatment. The H. pylori eradication rate
      was 91.4% in group A compared to 89.3% in group B (P-value not significant).
      Minor side-effects were reported in 4.2% of group A and 6.4% of group B patients.
      CONCLUSION: Rabeprazole showed good efficacy and tolerability in one-week H.
      pylori therapy at 20 mg b.i.d and 10 mg b.i.d, suggesting the use of the lower
      dosage.

PMID- 12795750
TI  - Rabeprazole treatment attenuated Helicobacter pylori-associated gastric mucosal
      lesion formation in Mongolian gerbils.
AB  - BACKGROUND AND AIM: Although rabeprazole (RPZ), a proton pump inhibitor, has been
      reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no
      studies have been conducted regarding the effect of RPZ on gastric mucosal lesion
      formation caused by this bacterium. In the present study, we investigated the
      effect of RPZ on H. pylori-associated gastric mucosal lesion formation. METHODS:
      Sixty-two male Mongolian gerbils were inoculated with H. pylori (ATCC43504) (Hp
      group) and 60 gerbils with the culture media alone (control group). Some gerbils
      in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for
      7 days) at the 5th week. Gerbils were evaluated at the 12th, 24th and 48th weeks.
      RESULTS: In the Hp group, all gerbils were persistently infected for 24 weeks,
      but 36% became negative for H. pylori at the 48th week. In the Hp + RPZ group,
      18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week,
      became negative for H. pylori. The level of neutrophil infiltration was
      significantly decreased in the Hp + RPZ group in comparison to the Hp group,
      possibly through the effects of RPZ on initial bacterial colonization and
      resultant inflammation. Even in the gerbils that became H. pylori-negative, the
      level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp
      group. RPZ treatment significantly increased the level of the reduced form of
      glutathione (GSH) at the 48th week. The elevated levels of the reduced form of
      GSH may have been reduced by an antioxidation process in the H. pylori-positive
      Hp + RPZ group. CONCLUSION: Administration of RPZ not only inhibited gastric H.
      pylori colonization, but also reduced gastric mucosal inflammation in gerbils,
      possibly through its antibacterial action as well as pharmacological recruitment
      of the reduced form of GSH.

PMID- 12795751
TI  - Validation of Rome II criteria for functional gastrointestinal disorders by
      factor analysis of symptoms in Asian patient sample.
AB  - BACKGROUND: It has been unclear as to whether the Rome II criteria could be
      applied to patients in the Asia region with functional gastrointestinal (GI)
      diseases. The aim of the present study was to determine if symptoms of Asian
      patients with functional gastrointestinal disorders formed groups which
      corresponded to the Rome II diagnostic criteria. METHODS: A modified English
      version of Talley's bowel disease questionnaire was developed in collaboration
      with various research teams in accordance with the Rome II criteria. This
      instrument was translated into the local languages of the following nine Asian
      regions: China, Hong Kong, Indonesia, Korea, Malaysia, Singapore, Taiwan,
      Thailand and Vietnam. From September to December 2001, newly enrolled outpatients
      attending 14 GI or medical clinics in these regions were invited to complete the
      questionnaire. From these respondents, patients with functional gastrointestinal
      disorders fulfilling the '12 weeks out of 12 months' criteria were separated for
      further analysis. Principal component factor analysis with varimax rotation was
      used to identify symptom clusters or factors. These factors were compared with
      the existing classification of functional GI diseases derived from the Rome II
      criteria. RESULTS: Factor analysis of symptoms from 1012 functional GI patients
      supported the Rome II classification of the following groups of functional GI
      disorders: diarrhea-predominant irritable bowel syndrome, functional
      constipation, functional dyspepsia, functional abdominal pain syndrome,
      functional heartburn, and functional vomiting. Functional diarrhea was combined
      with functional anorectal disorders, and globus merged with functional dysphagia
      into one factor. Some of the functional dyspepsia, abdominal bloating and
      belching symptoms were loaded into one factor. CONCLUSIONS: Factor analysis of
      symptoms from a sample of Asian patients with functional GI disorders partially
      supported the use of the Rome II classification.

PMID- 12795752
TI  - Alteration of aquaporin mRNA expression after small bowel resection in the rat
      residual ileum and colon.
AB  - BACKGROUND: Diarrhea occurring after small bowel resection gradually improves due
      to intestinal adaptation. It is known that several water channels, termed
      aquaporins (AQP), are expressed in the gastrointestinal tract and facilitate
      water transport. However, the changes of AQP after bowel resection remain
      unclear. In the present paper, the alterations in AQP mRNA expression were
      investigated after a massive small bowel resection in the rat residual ileum and
      colon. METHODS: The 6-week-old male Sprague-Dawley rats (n = 15) underwent an 80%
      distal small bowel resection. The residual ileum and colon were dissected on
      postoperative day 1, 3, 5 or 7 (n= 3 on each day). Total RNA was purified from
      each mucosa, and the expressions of AQP and sodium-dependent glucose transporter
      (SGLT1) mRNA were analyzed by northern blot. The plasma vasoactive intestinal
      polypeptide (VIP) concentrations on the preoperative day and postoperative day 1
      were assayed. RESULTS: In the residual small intestine, the expression of AQP-1
      and AQP-3 mRNA increased significantly on postoperative day 1. The AQP-7 mRNA
      increased on postoperative day 3, but the AQP-4 mRNA did not change after the
      bowel resection. The SGLT1 mRNA gradually decreased after the bowel resection. In
      the colon, the expression of AQP-3 increased on postoperative day 1 and 7, but
      AQP-4 mRNA did not change after surgery. The AQP-8 mRNA levels increased slightly
      on postoperative day 7. Plasma VIP concentration did not change between
      preoperative day and postoperative day 1. CONCLUSIONS: These results indicate
      that several AQP, except for AQP-4, were up-regulated after a massive small bowel
      resection, and that AQP might play important roles during adaptation.

PMID- 12795753
TI  - Simple method of preparation of rat colonocyte apical membranes using
      polyethylene glycol precipitation.
AB  - BACKGROUND: Although a number of methods are available for the preparation of
      brush border membranes (BBM) from the small intestine, very few studies have been
      performed on the isolation of colonic apical membranes (CAM). Cation
      precipitation is one of the methods used for the isolation of these membranes,
      which can result in altered lipid composition as a result of activation of
      phospholipase. We have earlier established a method for BBM isolation using
      polyethylene glycol (PEG) precipitation. In the present study, CAM from isolated
      colonocytes were prepared using PEG and the isolated membranes were
      characterized. METHODS: The CAM were prepared from isolated rat colonocytes using
      PEG precipitation and differential centrifugation. Purity was assessed by
      enrichment of the marker enzymes and contamination by other subcellular
      particles. Lipid composition and sugar components were analyzed in the isolated
      membranes. RESULTS: The CAM showed 11-12-fold enrichment in alkaline phosphatase
      and 9-10-fold enrichment in gamma-glutamyl transpeptidase as compared with the
      cell homogenate. The final membrane preparation also showed good vesicle
      formation as seen by electron microscopy. There was very little contamination of
      basolateral membranes, microsomes or lysosomes in the final membrane preparation.
      Analysis of sugars indicated high content of fucose and sialic acid as compared
      with hexoses. Lipid analysis indicated the presence of various neutral and
      phospholipids and a cholesterol/phospholipid ratio of 0.65 was seen. CONCLUSION:
      This study has shown a simple method of CAM preparation using PEG precipitation,
      which is less time-consuming than other methods and comparatively pure.

PMID- 12795754
TI  - Effects of lipopolysaccharide on the biliary excretion of bile acids and organic
      anions in rats.
AB  - BACKGROUND: Lipopolysaccharide is known to be a cause of cholestasis associated
      with sepsis. It has also recently been reported to down-regulate the basolateral
      and canalicular transporters. The aim of the present study was to examine
      simultaneously the effect of lipopolysaccharide on the biliary excretion of
      typical substrates of bile salt export pump and multidrug resistance protein 2 in
      vivo, and the effect of lipopolysaccharide on the amount of these transporters.
      METHODS: After intravenous administration of O127:B8-derived lipopolysaccharide
      (2.5 mg/kg), the biliary excretion of taurocholate and various organic anions was
      studied, and the protein levels of bile salt export pump and multidrug resistance
      protein 2 in the crude liver membrane was determined by western blot analysis.
      RESULTS: Lipopolysaccharide decreased the biliary excretion of tracer amounts of
      taurocholate, leukotriene C4, taurolithocholate-3-sulfate and temocapril without
      affecting bile flow. The biliary excretion of high doses of taurocholate and
      sulfobromophthalein was markedly inhibited by lipopolysaccharide.
      Lipopolysaccharide decreased bile salt export pump levels in the liver plasma
      membrane fraction to 48% of control rats, and markedly decreased multidrug
      resistance protein 2 levels to 17% of control rats. CONCLUSIONS: These findings
      support the hypothesis that down-regulation of the canalicular transporters by
      lipopolysaccharide causes the impairment of the biliary excretion of bile acids
      and organic anions in cholestasis of sepsis prior to the decrease of bile flow.

PMID- 12795755
TI  - Seroepidemiology of hepatitis A virus infection among school children in Delhi
      and north Indian patients with chronic liver disease: implications for HAV
      vaccination.
AB  - BACKGROUND: Universal vaccination against hepatitis A virus (HAV) has been
      recommended for children because of the changing epidemiological pattern of HAV.
      Vaccination has also been advised for patients with chronic liver disease as HAV
      superinfection in these patients can result in severe or even fatal disease. In
      India, the indications for HAV vaccination are not clear due to contradictory
      seroepidemiological data in children and lack of data on HAV seroprevalence in
      patients with chronic liver disease. METHODS: Sera were collected from children
      studying in two government-run schools and from patients with chronic liver
      disease attending the Liver Clinic at the All India Institute of Medical Sciences
      (AIIMS). The sera were tested for anti-HAV antibodies. The incidence of HAV
      induced acute hepatitis and acute liver failure at AIIMS over the last 10 years
      was also assessed. RESULTS: A total of 93.2% (1328/1424) of the school children
      between 4-18 years of age who were included in the study had anti-HAV antibody in
      their sera. Eighty percent of the children had antibodies against HAV in their
      sera by the age of 5 years, whereas all the children above 16 years were positive
      for anti-HAV antibody. A total of 256 patients with chronic liver disease (94
      with cirrhosis of the liver, 160 with chronic hepatitis) were tested for the
      presence of anti-HAV antibody. Of them, 97.6% (248/254) had anti-HAV antibody in
      their sera. The annual frequency of HAV-induced acute viral hepatitis and acute
      liver failure at AIIMS during the last 10 years did not show any change.
      CONCLUSION: Mass vaccination against HAV is not required in north India because
      of the presence of protective antibodies against HAV in the majority of the
      population.

PMID- 12795756
TI  - Preclinical study of endoscopic ultrasonography with electronic radial scanning
      echoendoscope.
AB  - BACKGROUND: To evaluate the imaging possibility of a newly designed electronic
      radial scanning echoendoscope (ER-ES). METHODS: In the in vivo study of swine, we
      obtained B-mode endoscopic ultrasonography (EUS) images of the gastric and
      gallbladder (GB) walls and checked the ability to detect Doppler signals using ER
      ES and electronic linear array echoendoscope (EL-ES). Furthermore, in the ex vivo
      study of swine, B-mode EUS images of fixed gastric and GB wall specimens were
      obtained using ER-ES, EL-ES and mechanical radial scanning echoendoscope (MR-ES).
      In the study of resected human specimens, we obtained B-mode EUS images of five
      resected GB specimens (three normal GB, one cholecystitis and one cancerous)
      using the three types of echoendoscope. RESULTS: In the in vivo study of swine,
      ER-ES and EL-ES depicted the gastric walls as five-layered, and the GB walls as
      single-layered structures. The ability to detect Doppler signals was equal
      between ER-ES and EL-ES. In the ex vivo study of swine, ER-ES, MR-ES and EL-ES
      equally delineated the gastric walls as five-layered and GB walls as three
      layered structures. In the study of resected human specimens, results
      demonstrated the normal GB walls as three-layered, the cholecystitis as a
      combination of outer high-echoic and inner low-echoic layers, and the cancer as a
      protruded tumor. CONCLUSIONS: We conclude that ER-ES has faculties for making B
      mode images as well as EL-ES and MR-ES. In addition, in the in vivo study, ER-ES
      can analyze blood flow information as well as EL-ES.

PMID- 12795757
TI  - Pretransplant hepatitis C virus infection and its effect on the post-transplant
      course of living renal allograft recipients.
AB  - BACKGROUND: Hepatitis C virus infection (HCV) is a main health problem in end
      stage renal disease (ESRD) patients. The effect of pretransplant HCV infection on
      survival among ESRD patients who have undergone renal transplantation is
      controversial. We report the results of a large monocenter study that evaluated
      the effect of hepatitis C on the patient, and on graft survival in renal
      transplanted patients who received living donated allograft. METHODS: A
      historical cohort study, we investigated all 1006 patients who received a living
      kidney transplant at Baghiatollah Medical Center in Tehran, Iran, between March
      1995 and October 2001 (up to 85 months follow up). Patients' sera had been
      routinely assayed for anti-HCV antibodies and hepatitis B surface antigen (HBsAg)
      at the time of transplantation. The HBsAg-positive patients were excluded from
      the survival analysis. Survivals were examined using Kaplan-Meier analysis and
      compared using the log-rank test. Multivariate analysis was performed using Cox's
      model. RESULTS: Forty-five patients (4.5%) were anti-HCV-antibody positive. Anti
      HCV-antibody-positive patients spent a longer time on dialysis and had a higher
      rate of retransplantation. There were no differences in recipients' sex and age
      and donors' age between the two groups. The 7-year patient survival rate was
      89.9% in the anti-HCV-antibody-positive group and 95.5% in the HCV-negative group
      (P = 0.74). Seven-year graft survival was 82.0% and 75.0% in the anti-HCV
      antibody-positive and HCV-negative groups, respectively (P = 0.39). In the
      multivariate analysis, age was the only significant parameter correlated with
      patient survival (P = 0.02). CONCLUSIONS: HCV infection does not seem to
      influence patient and graft survival within a medium-time follow up in living
      allograft recipients, and anti-HCV-antibody positive status (alone) is not a
      contraindication for renal transplantation. However, further studies are needed
      to better define the role of HCV infection in long-term prognosis.

PMID- 12795758
TI  - Australian women's experiences of living with hepatitis C virus: results from a
      cross-sectional survey.
AB  - BACKGROUND: Of the estimated 160000 Australians currently infected with the
      hepatitis C virus (HCV), over one-third are women and very few have received
      clinical treatment, with most managing their illness in non-specialist settings.
      Little is known about the experiences of women living with HCV in the general
      community. The present study provides the results from the first comprehensive
      social survey of Australian women's experiences of living with HCV. METHODS: In
      2000, a questionnaire was administered to a largely non-clinical sample of women
      with HCV (n = 462) living in the state of Victoria and the Australian Capital
      Territory, Australia. The questionnaire was self-administered with a return rate
      of 75%. The mean age was 35 years and 83% were 'current' or 'past' injecting drug
      users. The mean time since diagnosis was 4.6 years (SD = 4.0) and the mean time
      since infection was 10.5 years (SD = 8.2). RESULTS: Fifty-eight percent of women
      reported experiencing symptoms related to their HCV, the most common being
      tiredness (78%) and nausea (44%). Of the sample, 56% currently saw a doctor for
      their HCV, and while 52% had ever been referred to a specialist, only 17% of the
      total sample had ever begun interferon-based combination or monotherapy. Forty
      eight percent of women reported experiencing less favorable treatment by a health
      professional because of their HCV. Age-related self-assessed health status was
      significantly lower than Australian norms, as were SF-12 physical and mental
      health scores. The SF-12 physical and mental health scores were highly
      correlated, indicating a significant physical and mental health burden associated
      with HCV. CONCLUSION: The social, physical and mental health needs of women
      living with HCV are considerable. Most women had not accessed specialist
      treatment and the response of the primary health care system to HCV-related
      women's health issues requires improvement.

PMID- 12795760
TI  - Ethanol administration generates oxidative stress in the pancreas and liver, but
      fails to induce heat-shock proteins in rats.
AB  - BACKGROUND: Heat-shock proteins (HSP) play an essential role in the sequestration
      and reparation of denatured cellular proteins. Because ethanol treatment can
      result in oxidative stress-induced protein damage, it is possible that expression
      of HSP is altered after ethanol consumption. Dose-response and time-course
      studies were performed to investigate whether acute and chronic intragastric
      ethanol administration can induce tissue damage, oxidative stress and expression
      of the heat-shock proteins HSP60 and HSP72 in the pancreas and liver of male
      Wistar rats. METHODS: Laboratory and morphological analysis of pancreatic and
      liver damage were investigated. The degree of oxidative stress was assessed by
      measurement of the reduced glutathione content, lipid peroxidation and protein
      oxidation. The levels of HSP were examined by western blot analysis. RESULTS:
      Ethanol administration dose- and time-dependently elevated the serum ethanol
      concentration and hepatic enzyme activities. Chronic ethanol treatment also
      resulted in morphological damage of the liver. We observed that acute and chronic
      ethanol consumption had markedly different effects on the oxidative parameters in
      the pancreas and liver. Acute ethanol administration caused oxidative stress in
      the liver, whereas there was no such effect in the pancreas. In contrast, chronic
      ethanol feeding resulted in oxidative stress in both the pancreas and the liver.
      Furthermore, neither acute nor chronic ethanol intake induced the synthesis of
      HSP, a major defense system against cellular damage in the examined organs.
      CONCLUSION: Ethanol administration generates oxidative stress in the pancreas and
      liver, but fails to induce HSP in rats.

PMID- 12795759
TI  - Clinical usefulness of edaravone for acute liver injury.
AB  - BACKGROUND: Edaravone, a newly synthesized radical scavenger, has shown an
      excellent effect on treating stroke patients. The effect of edaravone on carbon
      tetrachloride (CCl4)-induced acute liver injury was examined. METHODS: Six rats
      were injected with CCl4 alone and six rats were intravenously injected with
      edaravone immediately after and 3 h after injection of CCl4. Another six rats
      were injected with olive oil alone. The animals were killed at 24 h after the
      CCl4 injection. RESULTS: Injection of CCl4 was followed by a marked increase in
      serum alanine aminotranferase (ALT) level (CCl4, 1630.6 +/- 606.8 IU/L; olive
      oil, 21.0 +/- 2.6 IU/L; P < 0.001), lactate dehydrogenase (LDH) level (CCl4,
      5068.0 +/- 2956.4 IU/L; olive oil, 203.6 +/- 30.5 IU/L; P < 0.005), and total
      bilirubin (TB) level (CCl4, 0.88 +/- 0.48 mg/dL; olive oil, 0.37 +/- 0.05 mg/dL;
      P < 0.01), whereas in the edaravone-treated rats, the ALT (119.4 +/- 113.5 IU/L,
      P < 0.001), LDH (369.7 +/- 288.2 IU/L, P < 0.005), and TB values (0.29 +/- 0.16
      mg/dL, P < 0.01) were significantly decreased. Histological examination of the
      liver by hematoxylin and eosin and oil red O staining showed a marked reduction
      of steatosis in the CCl4 and edaravone-treated rats compared with the CCl4
      injected rats. Significant inhibition of hepatocytic apoptosis was demonstrated
      by the terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling
      (TUNEL) method in the edaravone-treated rats. CONCLUSIONS: These results suggest
      that edaravone has a marked preventive effect on oxidative stress-induced acute
      liver injury.

PMID- 12795761
TI  - Utilization of hepatoprotectants within the National Health Insurance in Taiwan.
AB  - BACKGROUND: Although the hepatoprotectants of Western medicine have centuries of
      history, their utilization patterns have been seldom documented. Because the
      National Health Insurance program in Taiwan reimburses hepatoprotectant use, we
      could estimate the age- and sex-specific prevalence and utilization patterns of
      hepatoprotectants in Western medicine within the health insurance system in
      Taiwan. METHODS: We analyzed the outpatient prescription data of 50000 randomly
      sampled insured patients in 2000. Only patients using drugs indicated for liver
      diseases and diagnostic codes related to liver diseases on the same visit were
      considered to be receiving hepatoprotectants. Drugs involved in Chinese medicine
      were not included. RESULTS: Among the valid cohort of 46614 people, 783 (1.7%)
      were identified as patients with liver disease and receiving hepatoprotectants.
      Highest prevalence of hepatoprotectant use was 4.9% in the 60-69 years age group.
      Silymarin, multivitamins, methionine, ursodeoxycholic acid, and liver hydrolysate
      accounted for 88.8% of the 3215 prescribed items of hepatoprotectants. Patients
      receiving hepatoprotectants had, on average, visited the clinics more frequently
      than those not using hepatoprotectants (30 vs 14 times in a year, P < 0.001), and
      used more insurance benefits (US dollars 1352 vs US dollars 456, P < 0.001).
      CONCLUSIONS: The frequency of use of major hepatoprotectants in Taiwan
      corresponded to the current modalities of treatment under discussion worldwide.

PMID- 12795762
TI  - Hepatobiliary and pancreatic: arterioportal fistula causing portal hypertension.

PMID- 12795763
TI  - Gastrointestinal: bleeding colonic diverticulum.

PMID- 12795764
TI  - Expression of gastric mucin in the stomachs of two patients with Menetrier's
      disease: an immunohistochemical study.
AB  - Menetrier's disease is a rare gastric condition characterized by marked
      proliferation of the mucosa and variable mucus secretion and achlorhydria. We
      report, for the first time, minor variations in MUC1-7 distribution in the mucosa
      of two stomachs from patients with Menetrier's disease, when compared with a
      normal stomach. All stomachs stained positively for MUC4, 5AC and 6 and showed no
      or little staining with MUC2 and 3. Thus, Menetrier's disease is characterized by
      an excess quantity of mucus secretion, but differs little from normal stomachs
      with regards to the types of mucin produced. The mucins, MUC1-7, are found with
      variable distribution in different body tissues; MUC4, MUC5AC and MUC6 are
      typically found in gastric mucosa.

PMID- 12795765
TI  - A 1 mm depressed type IIC minute colorectal cancer: first reported case and
      discussion of clinical relevance, with special reference to endoscopic diagnosis.

PMID- 12795766
TI  - EM574, a motilide, has an orexigenic activity with affinity for growth-hormone
      secretagogue receptor.

PMID- 12795767
TI  - Successful use of mesalamine in the treatment of chronic segmental lesion in a
      case of ischemic colitis.

PMID- 12795768
TI  - The immunological basis of psoriasis.
AB  - Evidence that psoriasis is an immune-mediated disorder comes from laboratory
      studies, clinical observation, and use of targeted therapies. Immunohistochemical
      studies have shown that the majority of T cells in psoriatic plaques are CD45RO+
      memory-effector T cells that migrate into skin in recognition of an as yet
      undetermined antigen. There is also a predominance of Th1 cytokines, namely
      interferon gamma, in psoriatic plaques, in contrast to the predominance of Th2
      cytokines found in atopic dermatitis. The efficacy of therapeutic agents that
      target T cells, such as anti-CD4+ monoclonal antibodies, cyclosporin, and
      interleukin-2 fusion toxin, has provided further substantial evidence that
      psoriasis is a T-cell-mediated disease. New T-cell targeted approaches and
      cytokine modulation are advancing basic science in providing an understanding of
      the evidence for the importance of the immune process in the biology of
      psoriasis.

PMID- 12795769
TI  - Targeting T-cell subsets to achieve remission.
AB  - Patients with psoriasis have an increase in pathogenic CD45RO+ memory-effector T
      cells during active disease. The genetically engineered fully human fusion
      protein alefacept has been developed to selectively target this subset of T
      cells. Alefacept binds to memory-effector CD45RO+ T cells, inhibiting their
      activation and inducing T-cell apoptosis. The selectivity of alefacept for memory
      effector CD45RO+ T cells was evaluated in 229 patients with chronic psoriasis in
      a randomized, placebo-controlled, double-blind study conducted at 22 centres in
      the USA. Patients received alefacept intravenously at doses of 0.025 mg/kg, 0.075
      mg/kg, or 0.150 mg/kg, or placebo once weekly for 12 weeks. Two weeks after
      completing treatment, patients receiving alefacept showed significant improvement
      in the Psoriasis Area and Severity Index (PASI) compared with those receiving
      placebo. Mean reductions in the PASI score were up to 53% lower than baseline
      scores in the alefacept treatment group, compared with a 21% decline from
      baseline in the placebo group (P < 0.001). In addition to the significant
      improvement in psoriasis, treatment with alefacept produced long-term remission
      in some patients. Twelve weeks after completion of therapy, 28 patients became
      clear or almost clear. The therapy was well tolerated and nonimmunogenic.
      Importantly, during treatment, there was a correlation between improvement in
      psoriasis and a dose-dependent reduction in peripheral blood CD45RO+ memory
      effector T cells, but not in CD45RA+ naive T cells. This correlation indicates a
      relationship between a specific T-cell subset reduction (CD45RO+) and clinical
      outcome in psoriasis.

PMID- 12795770
TI  - Clinical response to alefacept: results of a phase 3 study of intramuscular
      administration of alefacept in patients with chronic plaque psoriasis.
AB  - BACKGROUND: Recognition of psoriasis as a T-cell-mediated immune disease has led
      to the development of various therapeutic approaches directed against the
      pathogenic T cells. Alefacept, a novel and selective biological recombinant
      protein, binds CD2 on T cells to block T-cell activation and proliferation and
      interacts with FcgammaRIII receptors on accessory cells to produce selective T
      cell apoptosis. OBJECTIVE: To demonstrate the efficacy and safety of once-weekly
      alefacept IM compared with placebo given for 12 weeks to patients with chronic
      plaque psoriasis. METHODS: Multicentre (63 sites in Europe, the USA, and Canada),
      randomized, double-blind, parallel-group study comparing 10 mg and 15 mg of
      alefacept and placebo administered IM once weekly for 12 weeks. Patients were
      followed for an additional 12 weeks after cessation of therapy. Patients were
      eligible for enrollment if they were > or = 18 years of age, had chronic plaque
      psoriasis for > or = 12 months involving > or = 10% body surface area, and had
      CD4+ T-cell counts at or above the lower limit of normal. RESULTS: 507 patients
      were enrolled into three treatment groups, which were well balanced for
      demographic, baseline disease characteristics, and treatment history. A
      significantly greater percentage of patients treated with alefacept 15 mg IM
      achieved > or = 75% PASI reduction from baseline 2 weeks after the last dose
      compared with placebo (21% vs. 5%, P < 0.001); 12% of patients treated with
      alefacept 10 mg IM reached this level of improvement (P = NS vs. placebo).
      Alefacept was well tolerated, with adverse events similar to that of placebo.
      CONCLUSIONS: Treatment with alefacept 15 mg IM provided highly significant
      improvements in all measures of psoriasis disease activity compared with placebo.
      Pharmacodynamic data confirmed that alefacept is a selective biological agent
      that reduces memory-effector T cells (CD4+CD45RO+ and CD8+CD45RO+), the source of
      the pathogenic mediators of psoriasis, while having relatively no effect on naive
      T-cell populations.

PMID- 12795771
TI  - Clinical response to alefacept: results of a phase 3 study of intravenous
      administration of alefacept in patients with chronic plaque psoriasis.
AB  - BACKGROUND: There is a current lack of safe and effective psoriasis therapies
      that provide patients with lasting remissions after treatment is discontinued.
      Alefacept, a novel and selective biological agent, has demonstrated durable
      efficacy in patients with chronic plaque psoriasis, and its efficacy has been
      correlated with reductions in memory-effector T cells. OBJECTIVE: To demonstrate
      the efficacy and safety of both one and two 12-week courses of alefacept 7.5 mg
      given once weekly as an intravenous (IV) bolus injection in patients with chronic
      plaque psoriasis. METHODS: Multicentre (51 centres in the USA and Canada),
      randomized, double-blind, parallel-group study comparing once-weekly alefacept
      7.5 mg IV or placebo for two 12-week treatment courses. Each course had a 12-week
      follow-up phase. Patients were eligible for enrollment if they were > or =16
      years of age, had chronic plaque psoriasis for > or =12 months involving > or
      =10% body surface area, and had CD4+ T-cell counts at or above the lower limit of
      normal. RESULTS: 553 patients received treatment in Course 1, and 449 were
      treated in Course 2. The cohorts were well balanced for demographic and baseline
      disease characteristics. During the treatment and follow-up period of Course 1,
      28% of patients treated with alefacept achieved > or =75% reduction in Psoriasis
      Area and Severity Index (PASI), compared with 8% of placebo-treated patients (P <
      0.001). Patients achieving > or =75% reduction in PASI following a single 12-week
      course of alefacept maintained > or =50% reduction in PASI for a median of over 7
      months. Among patients who received a second course of alefacept therapy, 71%
      achieved > or =50% reduction in PASI, and 40% achieved > or =75% reduction in
      PASI over two treatment courses. One or two 12-week courses of alefacept were
      similarly well tolerated. CONCLUSIONS: Treatment with alefacept 7.5 mg IV
      provided highly significant improvements in all measures of psoriasis disease
      activity compared with placebo. A second course of alefacept provided additional
      benefit.

PMID- 12795773
TI  - How useful is the "cocktail approach" for evaluating human hepatic drug
      metabolizing capacity using cytochrome P450 phenotyping probes in vivo?
AB  - Relatively selective in vivo substrate probes have been developed for several
      major CYP isoforms involved in oxidative drug metabolism. There are basically two
      in vivo methods for identifying the phenotype. One method, the selective (CYP
      specific) phenotyping method, involves administering one single probe drug,
      whereas the other is a mixed phenotyping or "cocktail" method involving the
      simultaneous administration of multiple probe drugs, specific for the individual
      P450. At present, caffeine and chlorzoxazone are used most often as probe drugs
      for CYP1A2 and CYP2E1, respectively, but these are not necessarily the best probe
      drugs. Of the potential probe drugs for CYP2C9, CYP2C19, CYP2D6 and CYP3A4, none
      is really useful. Despite current limitations, the cocktail method for obtaining
      information about multiple CYP activities in a single experimental session is
      likely to be more widely used as a screening or phenotyping method for humans in
      the future.

PMID- 12795774
TI  - Insulin resistance--the new goal!
AB  - Diabetes mellitus is a well-recognized risk-factor for coronary artery disease
      (CAD). Epidemiological studies have shown that the risk of CAD increases two to
      sixfold in patients with type 2 diabetes compared with those without the disease.
      Furthermore the prevalence of diabetes in the UK has increased by 30% since 1991
      and the world population of people with diabetes in 2010 is expected to be twice
      that of 1990. In addition whilst the mortality from CAD in patients without
      diabetes has declined over the past 20 years the mortality in men with type 2
      diabetes has not changed and in women may have increased. UKPDS and other studies
      have shown a significant improvement in the onset and course of microvascular
      complications with good diabetic control. However the same is not true for
      macrovascular complications for which there is no good evidence of improvement
      with better diabetic control. This apparent lack of benefit from improved care of
      diabetic patients has led to many different approaches. These include attempts to
      achieve even better glycaemic control, greater emphasis on other risk factors
      particularly hypertension and interestingly attention to the prediabetic state
      characterized by insulin resistance (IR). The latter is associated with a number
      of abnormalities which could play a causative role in the development of
      cardiovascular disease. This article will review the concept of IR and the
      possible interventions available to tackle it.

PMID- 12795775
TI  - Efficacy of permethrin-impregnated uniforms in the prevention of cutaneous
      leishmaniasis in Iranian soldiers.
AB  - BACKGROUND: One approach for prevention of cutaneous leishmaniasis (CL) is the
      creation of a barrier between the insect vector (phlebotoms) and the host. Many
      but not all researchers claim that permethrin-impregnated uniforms are effective
      for prevention of CL. We determined the efficacy of permethrin-impregnated
      uniforms for prevention of CL in Iranian soldiers. METHODS: A total of 324
      soldiers were randomized to two equal groups, of which 272 soldiers completed the
      study. In group A, 134 soldiers were issued permethrin-impregnated uniforms. In
      group B, 138 soldiers were issued uniforms washed in water. The soldiers wore
      uniforms day and night for 3 months, and were observed for an additional period
      of 6 months. All the soldiers remained in the leishmania-endemic area of Isfahan
      during the 3 months. RESULTS: Nine (6.5%) of 138 soldiers wearing control
      uniforms and six (4.4%) of 134 soldiers wearing permathrin-impregnated uniforms
      acquired CL. The difference between two groups was not statistically significant
      (P < 0.05). CONCLUSION: Permethrin-impregnated uniforms are not effective for the
      prevention of CL.

PMID- 12795776
TI  - A comparison of the beta1-selectivity of three beta1-selective beta-blockers.
AB  - OBJECTIVE: To determine the relative beta1-selectivity of three beta-blockers
      (nebivolol, bisoprolol and atenolol), administered orally at normal therapeutic
      doses, by assessing their impact on the beta2-mediated, haemodynamic and
      biochemical responses to a terbutaline infusion, which decreases serum potassium
      and increases serum glucose and insulin. METHODS: Twenty-four healthy volunteers
      (14 men, 10 women), with no history of respiratory disease, attended on five
      separate occasions; beta-blockers (nebivolol 5 mg, bisoprolol 10 mg, atenolol 50
      and 100 mg) or placebo were supplied in random order. Three baseline blood
      samples were collected at 65-85 min post-beta-blocker. A 60-min terbutaline
      infusion was started 90 min after taking the beta-blocker. Blood samples were
      taken and blood pressure and heart rate recorded at 15 min intervals up to 30-min
      post-infusion. Blood samples were analysed for serum potassium, glucose and
      insulin concentrations. RESULTS: Terbutaline increased heart rate. Pretreatment
      with nebivolol caused a modest and non-significant reduction in terbutaline
      induced tachycardia whilst bisoprolol produced a more marked effect. Atenolol at
      both 50 and 100 mg doses caused a highly significant reduction in terbutaline
      induced tachycardia. All active preparations had a comparable impact on the
      terbutaline-induced increase in systolic blood pressure, but the drugs had no
      impact on the changes produced in diastolic blood pressure. After pretreatment
      with placebo, the terbutaline infusion caused a significant decrease in serum
      potassium and increases in serum glucose and insulin. Pretreatment with nebivolol
      had no discernible effect on potassium compared with placebo. In contrast, when
      compared with either placebo or nebivolol, bisoprolol (P < 0.01) and both doses
      of atenolol (P < 0.001) significantly attenuated the hypokalaemic effect of
      terbutaline. Treatment with nebivolol and bisoprolol modestly but significantly
      reduced the terbutaline-induced increases in glucose (P < 0.05). The blocking
      effects of both doses of atenolol were highly significant (P < 0.001) when
      compared with placebo and also significant (P < 0.05 and P < 0.01, respectively)
      when compared with nebivolol and bisoprolol. A similar pattern of responses with
      the different beta-blocker treatments was observed for the effects on insulin
      concentrations during the terbutaline infusion. CONCLUSION: The beta1-selectivity
      of three different beta1-blockers has been demonstrated in healthy volunteers
      using the blocking of biochemical and haemodynamic responses to a beta2 stimulus.
      Terbutaline alone caused an increase in heart rate, a rise in systolic blood
      pressure, a fall in serum potassium and a rise in both serum glucose and insulin.
      In this study, for both haemodynamic and biochemical responses, atenolol 100 mg
      had the greatest beta2-blocking effect, nebivolol 5 mg the least. Bisoprolol 10
      mg and atenolol 50 mg had intermediate effects; bisoprolol was the more beta1
      selective of these two.

PMID- 12795777
TI  - Average bioequivalence study of clarithromycin tablets in healthy male
      volunteers.
AB  - OBJECTIVE: To evaluate the average bioequivalence of two formulations of 500 mg
      clarithromycin tablets in 24 healthy Thai male volunteers. METHODS: In a
      randomized, single dose, fasting state, two-period, crossover study design with a
      1-week washout period, each subject received a 500 mg clarithromycin tablet.
      Plasma samples were collected over a 24-h period after administration and were
      analysed by using a validated HPLC-ECD method. Pharmacokinetic parameters were
      determined by using non-compartmental analysis. RESULTS: The time to reach the
      maximal concentration (tmax, h), the peak concentration (Cmax, ng/mL) and the
      area under the curve (AUC0- infinity, ng h/mL) of the Reference and Test
      formulations were 2.0 +/- 0.9 vs. 1.8 +/- 1.1, 3018 +/- 841 vs. 3014 +/- 752 and
      23142 +/- 7348 vs. 22810 +/- 6027, respectively. The 90% confidence interval of
      Cmax and AUC0- infinity were 90.6-109.4 and 89.6-110.1%. CONCLUSION:
      Bioequivalence between the Test and Reference formulation can be concluded.

PMID- 12795778
TI  - Use of gabexate mesylate in Italian hospitals: a multicentre observational study.
AB  - INTRODUCTION: Gabexate mesylate has been proposed as a therapeutic or
      prophylactic agent in a variety of diseases (e.g. disseminated intravascular
      coagulation, prophylaxis of pancreatic damage and acute pancreatitis), but its
      clinical effectiveness is still unclear. As the drug is widely used in Italy, we
      conducted an observational study to determine the pattern of prescription of
      gabexate in Italian hospitals and to assess the outcome of patients with acute
      pancreatitis when this treatment is given. An updated meta-analysis of the use of
      the drug is also presented. MATERIALS AND METHODS: From 20 May to 20 July 2001,
      all consecutive patients admitted to 13 Italian hospitals were enrolled. The
      following information was recorded from each patient: indication for the use of
      gabexate, total dose and duration of gabexate administration, need for surgical
      treatment and outcome of hospitalization (alive or dead). In the patient subgroup
      with acute pancreatitis, the outcome data of our observational study were
      compared with those reported by the randomized trials (RCTs) previously
      published. For this purpose, the survival data of the RCTs were summarized in an
      updated meta-analysis. RESULTS: A total of 170 patients were enrolled in the
      study. The main clinical indications were acute pancreatitis in 88 cases (52%)
      and prophylaxis of pancreatic damage in 62 cases (36%). At the end of the study,
      80 of the 88 patients treated for acute pancreatitis (91%) were alive and eight
      (9%) had died. In the subgroup of patients with necrotic-haemorrhagic
      pancreatitis (n = 10), six died during the observation period. Our meta-analysis
      showed that gabexate mesylate did not improve survival in comparison with
      placebo. The meta-analytic odds ratio was 0.70 (95% CI: 0.45-1.09). DISCUSSION:
      The study described the pattern of use of gabexate mesylate in Italian hospitals
      and provided information on the outcome of the subgroup treated for acute
      pancreatitis. A meta-analysis of current data from RCTs, together with our
      findings, indicates that gabexate mesylate does not significantly improve
      survival in acute pancreatitis.

PMID- 12795779
TI  - What are the non-biomedical reasons which make family doctors over-prescribe
      antibiotics for upper respiratory tract infection in a mixed private/public Asian
      setting?
AB  - OBJECTIVES: To examine the non-biomedical reasons which make family doctors over
      prescribe antibiotics for upper respiratory tract infection (URTI) in a mixed
      private/public Asian setting. METHODS: The questionnaire was sent to the members
      of the Hong Kong College of Family Physicians between August and December 2001.
      RESULTS: A total of 801 family doctors completed a postal questionnaire with an
      overall response rate of 65.0. A significant number of respondents (21.8) felt
      they might be prescribing antibiotics too often for URTI but the majority of them
      felt they were using antibiotics just a bit too often. Doctors who were older,
      more senior or in private practice were more likely to feel that they might be
      prescribing antibiotics too often. More than 50 of respondents thought that to
      satisfy the patient or his/her carer and fear of medicolegal problem if the
      patient deteriorates would make them very likely or likely to over-prescribe
      antibiotics for patients with URTIs. Public doctors might over-prescribe in order
      to save time, whereas private doctors might do so in order to keep patients in
      their practice. CONCLUSION: The results showed that doctors with certain
      characteristics are more likely to over-prescribe antibiotics. Factors, other
      than biomedical ones, may play important roles in doctor's prescription of
      antibiotics for URTI.

PMID- 12795780
TI  - Structure-activity relationship: analyses of p-glycoprotein substrates and
      inhibitors.
AB  - OBJECTIVE: A large number of structurally and functionally diverse compounds act
      as substrates or modulators of p-glycoprotein (p-gp). Some of them possess
      multiple drug resistance (MDR)-reversing activity, but only a small number of
      them have entered clinical study. In order to uncover the factors which exert a
      significant impact on the interaction between substrates/modulators and p-gp, we
      have performed structure-activity relationship (SAR) analyses, including
      molecular modelling, two-dimensional (2D) and three-dimensional (3D) parameter
      frame-setting analysis, quantitative structure activity relationship (QSAR)
      analysis among substrates/modulators, as well as clinically promising MDR
      reversing agents. METHODS: The physicochemical parameters C log P, CMR and all
      regression equations were derived by using C log P version 4.0 and the latest
      CQSAR software, respectively. Molecular modelling and all other parameter
      calculations were performed by using HyperChem version 5.0 program, after
      geometry optimization and energy minimization using the AM1 semiempirical method.
      RESULTS: SAR analyses indicate that MDR reversal activity is correlated with the
      lipophilicity (C log P), molecular weight (log Mw), longest chain (Nlc) of the
      molecule and the energy of the highest occupied orbital (Ehomo). In addition, the
      presence of a basic tertiary nitrogen atom in the structure is also an important
      contributor to p-gp inhibitory activity. Some separation in space is achieved for
      different subsets of p-gp substrates and inhibitors using Nlc, C log P and Ehomo
      as three independent parameters in the 3D-parameter-frame setting. CONCLUSION: A
      highly effective p-gp modulator candidate should possess a log P value of 2.92 or
      higher, 18-atom-long or longer molecular axis, and a high Ehomo value, as well as
      at least one tertiary basic nitrogen atom. The results obtained may be useful in
      explaining drug-p-gp interactions for different compounds, including drug
      interactions and the development of new MDR chemosensitizers.

PMID- 12795781
TI  - Facile and rapid high-performance liquid chromatography method for simultaneous
      determination of allopurinol and oxypurinol in human serum.
AB  - OBJECTIVE: To develop a rapid and sensitive assay for the simultaneous
      determination of allopurinol and oxypurinol in serum. METHOD: High-performance
      liquid chromatography (HPLC) with UV-detection. Sample preparation consists of
      protein precipitation by an addition of trichloracetic acid. RESULTS: Percentage
      recovery and intra-assay coefficient of variation (CV%) for allopurinol were 97.4
      101.3 and 0.66-5.13, respectively, in the concentration range 0.5-5.0 microg/mL.
      For oxypurinol, the percentage recovery and the intra-assay CV% were 93.2-98.1
      and 0.88-5.62, respectively, in the concentration ranges 0.4-20 microg/mL. There
      was no interference of endogenous compounds in this assay. CONCLUSION: This
      method is useful for routine therapeutic drug monitoring of allopurinol in a
      clinical setting.

PMID- 12795782
TI  - (R,S)-salbutamol plasma concentrations in severe asthma.
AB  - OBJECTIVE: Salbutamol is commonly delivered as a racemic mixture of
      pharmacologically active (R)-salbutamol and inactive (S)-salbutamol. This study
      investigated inactive (S)- and active (R)-salbutamol plasma levels and their
      relationship to dose in patients with severe asthma. METHODS: Basic demographics,
      racemic-salbutamol dose in the preceding 24 h, lung function tests at baseline
      and 1 h, and a 10 mL plasma sample were obtained from subjects presenting to the
      Department of Emergency Medicine with acute asthma. Plasma determinations were
      carried out using an LC-MS assay with solid phase extraction. RESULTS: All
      patients (n = 5) had detectable levels of drug in plasma with range of 0.9-7.7
      and 4.7-27.4 ng/mL for (R)-salbutamol and (S)-salbutamol respectively. These were
      correlated to total racemic salbutamol dose. The range of the (S) : (R) ratio was
      2.0-5.2, with (R)-salbutamol representing 16-33% of the total plasma
      concentration, which did not correlate with total salbutamol dose. CONCLUSION:
      Only a small fraction of total plasma salbutamol concentration was found to
      consist of active enantiomer in patients with an acute severe exacerbation of
      asthma actively undergoing treatment with racemic-salbutamol. As a result of the
      possible contribution of (S)-salbutamol to poor asthma control further
      enantioselective investigations are warranted in severe asthma.

PMID- 12795783
TI  - Sulphasalazine-induced leucopenia in a patient with renal dysfunction.
AB  - BACKGROUND: Sulphasalazine is used for the long-term maintenance therapy of
      ulcerative colitis to prevent the relapse of symptoms. However, its clinical use
      is often restricted by its serious adverse effects. OBJECTIVE: Leucopenia
      occurred in a patient with severe renal dysfunction after administration of
      sulphasalazine. The present study was designed to examine whether the adverse
      event was associated with a disability in the metabolism of sulphasalazine.
      SUBJECT: A 29-year-old male patient with ulcerative colitis, who underwent
      haemodialysis thrice a week because of severe renal dysfunction. The chief
      complaint was diarrhoea. METHODS: Serum concentrations of three major metabolites
      of sulphasalazine, (5-aminosalicylic acid, sulphapyridine and N-acetyl
      sulphapyridine), were measured. The polymorphism of N-acetyltransferase 2, an
      enzyme that metabolizes sulphapyridine, was also determined by polymerase chain
      reaction. RESULTS: The trough levels of 5-aminosalicylic acid, sulphapyridine and
      N-acetyl-sulphapyridine were 0.77-1.45 microg/mL, 31.20-39.25 microg/mL and 14.19
      15.03 microg/mL, respectively. The gene diagnosis of N-acetyltransferase 2
      suggested that the type was classified as NAT2*6A/*7B, indicating that the
      patient was a slow acetylator. CONCLUSION: The patient was a slow acetylator,
      which might lead to a rise in the serum sulphapyridine concentration. Moreover,
      the decrease in protein binding of sulphasalazine as a result of severe renal
      dysfunction might have potentiated the effect because of the extremely high
      protein binding of this compound. Thus, it is most likely that these two factors
      contributed to the sulphasalazine-induced leucopenia.

PMID- 12795784
TI  - Use of pharmacoeconomics in prescribing research. Part 3: Cost-effectiveness
      analysis--a technique for decision-making at the margin.
AB  - This is the third Research Note addressing pharmacoeconomics in prescribing
      research, reflecting the increasing use of economic evaluation in drug purchasing
      decisions in a variety of settings. In this segment we provide an overview of the
      theoretical basis, practical application and methodological limitations of cost
      effectiveness analysis (CEA).

PMID- 12795785
TI  - Treatment of peri-implant infections: a literature review.
AB  - OBJECTIVES: The purpose of the present paper is to review available information
      on the treatment of peri-implant mucositis and peri-implantitis. MATERIALS AND
      METHODS: The results of animal research and human studies are presented. Proposed
      strategies for the treatment of peri-implantitis presented in the literature are
      also included. RESULTS: Most of the information accessible at this time derives
      from case reports. The reports provide evidence that efforts to reduce the
      submucosal infection may result in short-term improvements of the peri-implant
      lesion. They also indicate that regenerative procedures in intrabony peri-implant
      defects can result in the formation of new bone. CONCLUSIONS: Several
      uncertainties remain regarding the treatment of peri-implantitis. Properly
      conducted long-term follow-ups of consecutively treated cases would seem to be a
      realistic avenue for accumulation of more information. This may assist in
      establishing the predictability, magnitude and stability of improvements that can
      be achieved.

PMID- 12795787
TI  - Microsurgical access flap and enamel matrix derivative for the treatment of
      periodontal intrabony defects: a controlled clinical study.
AB  - OBJECTIVES: Application of the guided tissue regeneration (GTR) principle and
      utilization of enamel matrix derivative (EMD) have both been shown to result in
      periodontal regeneration. While clinical investigations have demonstrated that
      the use of a microsurgical concept in combination with the GTR technique
      positively affects the percentage of primary closure and the amount of tissue
      preservation, no such information is available for EMD-treated periodontal
      defects. It was the aim of the present investigation to assess the clinical
      effect of the microsurgical access flap and EMD treatment with an emphasis on the
      evaluation of early wound healing. MATERIAL AND METHODS: Eleven patients
      displaying at least one pair of intrabony periodontal defects with an intrabony
      component of > or =3 mm participated in the study. At baseline and at 6 and 12
      months after surgery, the following clinical parameters were assessed by a
      blinded examiner: oral hygiene status (API), gingival inflammation (BOP), probing
      pocket depth (PPD), clinical attachment level (CAL) and gingival recession (GR).
      Defects were randomly assigned to test or control treatment, which both consisted
      of a microsurgical access flap procedure designed for maximum tissue
      preservation. The exposed root surfaces of the test sites were conditioned with a
      24% EDTA gel followed by EMD (Emdogain(R)) application. Primary flap closure was
      achieved by a 2-layered suturing technique. Postoperative healing was evaluated
      by a newly introduced early wound-healing index (EHI) at 1 and 2 weeks after
      surgery. RESULTS: Both test and control treatment resulted in a statistically
      significant mean CAL gain of 2.8 and 2.0 mm at 6 months, and 3.6 and 1.7 mm at 12
      months, respectively (p<0.05). Differences in CAL gain between the two treatment
      modalities were statistically significant at both time points (p<0.05).
      Additional GR values after 12 months averaged 0.3 and 0.4 mm for test and control
      sites, respectively, and did not reach statistical significance (p> or =0.05).
      Two weeks after surgery, primary closure was maintained in 89% of the test sites
      and in 96% of the control sites. CONCLUSION: Both treatment modalities using the
      microsurgical flap procedure resulted in a high percentage of primary flap
      closure and maximum tissue preservation. In terms of PPD reduction and CAL gain,
      the combination with EMD application appeared to be superior to the microsurgical
      access flap alone.

PMID- 12795786
TI  - Deproteinized bovine bone and gentamicin as an adjunct to GTR in the treatment of
      intrabony defects: a randomized controlled clinical study.
AB  - OBJECTIVES: To evaluate whether Bio-Oss used as an adjunct to guided tissue
      regeneration (GTR) improves the healing of 1- or 2-wall intrabony defects as
      compared with GTR alone, and to examine whether impregnation of Bio-Oss with
      gentamicin may have an added effect. MATERIAL AND METHODS: Sixty patients, with
      at least one interproximal intrabony defect with probing pocket depth (PPD) > or
      =7 mm and radiographic evidence of an intrabony component (IC) > or =4 mm, were
      treated at random with either a resorbable membrane (GTR), a resorbable membrane
      in combination with Bio-Oss impregnated with saline (DBB-), a resorbable membrane
      in combination with Bio-Oss impregnated with gentamicin (DBB+), or with flap
      surgery (RBF). RESULTS: All treatment modalities resulted in statistically
      significant clinical improvements after 1 year. Defects treated with GTR alone
      presented a probing attachment level (PAL) gain of 2.9 mm, a residual PPD (PPD12)
      of 4.9 mm, a radiographic bone level (RBL) gain of 3.1 mm, and a residual IC
      (IC12) of 2.7 mm. GTR combined with Bio-Oss did not improve the healing outcome
      (PAL gain: 2.5 mm; PPD12: 4.9 mm; RBL gain: 2.8 mm; IC12: 3.3 mm). Impregnation
      of the Bio-Oss with gentamicin 2% mg/ml resulted in clinical improvements (PAL
      gain: 3.8 mm; PPD12: 4.2 mm; RBL gain: 4.7 mm; IC12: 2.1 mm), superior to those
      of the other treatment modalities, but the difference was not statistically
      significant. Defects treated with only flap surgery showed the most inferior
      clinical response (PAL gain: 1.5 mm; PPD12: 5.1 mm; RBL gain: 1.2 mm; IC12: 4.2
      mm) of all groups. CONCLUSION: The results failed to demonstrate an added effect
      of Bio-Oss implantation in combination with GTR on the healing of deep
      interproximal 1- or 2-wall, or combined 1- and 2-wall intrabony defects compared
      with GTR alone. Local application of gentamicin, on the other hand, improved the
      treatment outcome but not to an extent that it was statistically significant.

PMID- 12795788
TI  - Displacement amplitude of ultrasonic scaler inserts.
AB  - OBJECTIVES: Scanning laser vibrometry is a noninvasive method of measuring the
      velocity, displacement amplitude and oscillation frequency of vibrating objects.
      The purpose of this study was to assess, using a scanning laser vibrometer (SLV),
      the performance of different designs of commercially available ultrasonic scaler
      generators by measuring the oscillatory characteristics of various scaler tips.
      METHODS: Four ultrasonic generators were tested (Cavitron SPS and Cavitron Select
      (Dentsply, York, PA, USA) and Piezon Master 400 and Mini Piezon (Electro-Medical
      Systems, Switzerland)) with various designs of scaler tip. The tips were
      positioned with their anterior surface perpendicular to the direction of the
      laser. A graduated scale, placed over the manufacturer's power dial, enabled
      incremental power setting selection. For each power setting, the laser beam from
      the SLV was scanned over the surface of the oscillating tip. RESULTS: The ranges
      of longitudinal displacement amplitudes (in micrometres) were as follows: Mini
      Piezon (P-tip): 12.90+/-1.44 to 44.03+/-7.80; Piezon Master 400 (P-tip): 16.02+/
      2.66 to 35.85+/-5.29; Cavitron SPS (TFI-10 tip): 7.81+/-0.51 to 29.70+/-1.12;
      Cavitron Select (TFI-10 tip): 13.13+/-1.44 to 33.77+/-4.27; Cavitron SPS (TFI-3
      tip): 5.50+/-0.46 to 31.35+/-3.62. CONCLUSIONS: This study shows that there are
      differences between commercially available generators and that tip movement
      varies between tips of the same style as well as between the generator and tip
      design. Users of ultrasonic scalers should be made aware of this inherent
      variability that may influence clinical procedures.

PMID- 12795789
TI  - Efficacy of subgingival calculus removal with Er:YAG laser compared to mechanical
      debridement: an in situ study.
AB  - OBJECTIVES: The aim of the present study was to compare the effectiveness of
      subgingival calculus removal from periodontally involved root surfaces with an
      Er:YAG laser compared to hand instrumentation in situ. METHODS: The mesial and
      distal surfaces of 30 single-rooted teeth with untreated periodontitis were
      treated either by hand instrumentation (scaling and root planing (SRP)) or by
      Er:YAG laser irradiation with the aim of achieving a calculus-free root surface.
      Subgingival plaque samples were obtained before and immediately after treatment
      for microbiological evaluation by culture and DNA probe analysis. The teeth were
      extracted and the residual calculus was measured by means of digitized
      planimetry. The morphology of the root surface was evaluated by scanning electron
      microscopy, and undecalcified sections were analyzed to determine residual
      calculus and the extent of cementum removal following both treatments. RESULTS:
      Following laser irradiation, 68.4+/-14.4% of the root surface was calculus free
      in contrast to 93.9+/-3.7% after SRP when both treatments were performed for the
      same time (2:15+/-1:00 min). If laser irradiation was allowed twice the time used
      for hand instrumentation, 83.3+/-5.7% of the root surface was devoid of calculus.
      The effectiveness of both treatments was not related to initial probing depth.
      The histologic evaluation showed that after SRP 73.2% of root dentin was
      completely denuded from cementum, while only a minimal cementum reduction was
      apparent after laser irradiation. Both treatment modalities resulted in a similar
      reduction of periodontopathogens. DISCUSSION: The present investigation could
      demonstrate the in vivo capability of the Er:YAG laser to remove calculus from
      periodontally involved root surfaces, although the effectiveness did not reach
      that achieved by hand instrumentation. The lack of cementum removal in contrast
      to SRP may qualify the laser as an alternative approach during supportive
      periodontal therapy.

PMID- 12795790
TI  - Analysis of the TGF-beta1 promoter polymorphism (C-509T) in patients with chronic
      periodontitis.
AB  - BACKGROUND: A polymorphism in the promoter region of the transforming growth
      factor beta-1 (TGF-beta1) gene was described at position -509. This polymorphism
      represents a C-to-T base exchange, which creates a YY1 consensus sequence in an
      area involved with down transcription regulation. This polymorphism has been
      associated with risk for asthma and allergies. In this study we investigated the
      association between this polymorphism and chronic periodontitis severity.
      METHODS: Genomic DNA from oral mucosa of 87 Caucasian subjects was amplified by
      PCR, and digested with Eco81I restriction endonuclease. The alleles were
      separated by polyacrylamide gel electrophoresis. The differences in genotype
      distribution from those expected by Hardy-Weinberg equilibrium, and the
      significance of the differences in observed frequencies of the polymorphism in
      moderate and severe disease and healthy groups were assessed by the chi2 test.
      RESULTS: There was a difference in the presence of the different alleles and
      genotypes among the healthy, moderate and severe periodontitis groups. The allele
      T was seen at 57.7% in the group with severe periodontitis and 37.8% and 35.4% in
      the healthy group and moderate periodontitis group, respectively (p=0.0387). The
      genotype T/T was found at 38.5% in the group with severe periodontitis, and at a
      frequency of 8% in the healthy group (p=0.0258). CONCLUSION: These results
      demonstrate that the polymorphism at bp -509 in the TGF-beta1 promoter may have a
      small effect on the modulation of the inflammatory process during periodontitis.

PMID- 12795791
TI  - Tumor necrosis factor-alpha gene (TNF-alpha) -1031/-863, -857 single-nucleotide
      polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese.
AB  - OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) participate in the establishment of inflammatory lesions in periodontitis.
      High production of these cytokines may relate to the severity of periodontitis.
      There have already been several studies examining the association between
      periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine
      productivity. Recently, new SNPs of TNF-alpha, -1031, -863 and -857, variants of
      which are observed in a relatively large proportion in Japanese, have been
      identified. The variant alleles of these SNPs have been suggested to be related
      to high TNF-alpha production. For a better understanding of the genetic factors
      associated with the severity of periodontitis, further analysis including these
      newly identified SNPs is essential. In addition, previous reports on TNF-alpha or
      IL-1beta SNPs associated with periodontitis were mainly for Caucasian
      populations. Therefore, the aim of this study is to examine the association
      between severe periodontitis in Japanese and the following SNPs: five in the TNF
      alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta
      gene (-511, -31, +3953). MATERIAL AND METHODS: A total of 128 Japanese
      individuals were enrolled in this study. They were 64 patients with severe adult
      periodontitis and 64 healthy subjects. TNF-alpha and IL-1beta SNPs were genotyped
      by polymerase chain reaction-restriction fragment length polymorphism for all
      subjects. TNF-alpha and IL-1beta production from LPS-stimulated
      monocytes/macrophages was also measured for 15 healthy male subjects. RESULTS:
      TNF-alpha production in TNF-alpha-1031/-863 (linkage disequilibrated) or -857 SNP
      variant allele carriers tended to be elevated, and the frequency of subjects who
      carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs among
      severe periodontitis patients was significantly higher than in healthy subjects.
      CONCLUSION: Since the frequency of subjects who carried at least one variant
      allele in TNF-alpha-1031, -863 or -857 SNPs was higher in periodontitis patients
      than in healthy subjects, TNF-alpha-1031, -863 and -857 SNPs appear to be
      associated with severe adult periodontitis in Japanese populations.

PMID- 12795792
TI  - Acquisition and loss of Porphyromonas gingivalis, Actinobacillus
      actinomycetemcomitans and Prevotella intermedia over a 5-year period: effect of a
      triclosan/copolymer dentifrice.
AB  - OBJECTIVES: The present study describes the natural history of Porphyromonas
      gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a
      5-year period and the effect of a triclosan/copolymer dentifrice on these
      organisms in a normal adult population. MATERIAL AND METHODS: Subgingival plaque
      samples were collected from 504 adult volunteers. Probing pocket depths (PPD) and
      relative attachment levels were measured using an automated probe. Participants
      were matched for disease status (CPI), plaque index, age and gender, and
      allocated to receive either a triclosan/copolymer or placebo dentifrice. Re
      examination and subgingival plaque sampling was repeated after 1, 2, 3, 4 and 5
      years. P. gingivalis, A. actinomycetemcomitans and P. intermedia were detected
      and quantitated using an enzyme linked immunosorbent assay. Logistic regression
      and generalised linear modelling were used to analyse the data. RESULTS: This 5
      year longitudinal study showed considerable volatility in acquisition and loss
      (below the level of detection) of all three organisms in this population.
      Relatively few subjects had these organisms on multiple occasions. While P.
      gingivalis was related to loss of attachment and to PPD >/=3.5 mm, there was no
      relationship between A. actinomycetemcomitans or P. intermedia and disease
      progression over the 5 years of the study. Smokers with P. gingivalis had more
      PPD >/=3.5 mm than smokers without this organism. There was no significant effect
      of the triclosan dentifrice on P. gingivalis or A. actinomycetemcomitans.
      Subjects using triclosan were more likely to have P. intermedia than those not
      using the dentifrice; however this did not translate into these subjects having
      higher levels of P. intermedia and its presence was uniform showing no signs of
      increasing over the course of the study. CONCLUSION: The present 5-year
      longitudinal study has shown the transient nature of colonisation with P.
      gingivalis, A. actinomycetemcomitans and P. intermedia in a normal adult
      population. The use of a triclosan-containing dentifrice did not lead to an
      overgrowth of these organisms. The clinical effect of the dentifrice would appear
      to be independent of its antimicrobial properties.

PMID- 12795793
TI  - Activation of human matrix metalloproteinase 2 by gingival crevicular fluid and
      Porphyromonas gingivalis.
AB  - AIM: To assess the potential of gingival crevicular fluid (GCF) from adult
      periodontitis patients and Porphyromonas gingivalis proteases to activate matrix
      metalloproteinase 2 (MMP-2) in vitro. MATERIAL AND METHODS: GCF samples were
      collected from each of 15 adult periodontitis patients, from a clinically healthy
      site, a deep (>6 mm) bleeding site, and a deep nonbleeding site. The GCF samples
      were examined for general proteolytic activity, gelatinolytic activity and
      ability to activate pro-MMP-2 by zymography. Ultrasonic extracts of a range of
      clinical isolates of P. gingivalis cells and purified arg- and lys-gingipains
      were also assessed for their ability to activate pro-MMP-2. RESULTS: GCF from
      deep nonbleeding sites showed higher general proteolytic activity than samples
      from deep bleeding and healthy sites but this did not reach statistical
      significance. Pefabloc, a general serine protease inhibitor, inhibited the
      majority (92%) of the proteolytic activity. GCF samples contained neutrophil MMP
      9 in its latent form in 93% of the samples, and in its activated form in 40% of
      the samples. In contrast, MMP-2 was present in only trace amounts in 9% of the
      samples. When latent MMP-2 was added to these GCF samples, it was converted to
      the activated form (59 kDa) in 68% of the samples. Lower molecular weight (55 and
      45 kDa) activated forms also appeared in 53% of the samples, particularly those
      from deep sites. Activation to the 55 and 45 kDa forms was inhibited by MSAAPket
      (a neutrophil elastase inhibitor), whereas Pefabloc completely inhibited the
      activation of latent MMP-2. All ultrasonic extracts of P. gingivalis activated
      latent MMP-2 in a concentration- and time-dependent manner. Also, latent MMP-2
      was activated by purified arg-gingipain but less efficiently by lys-gingipain.
      CONCLUSION: These findings suggest that P. gingivalis arg-gingipain and
      neutrophil elastase present in GCF can activate latent MMP-2, which may
      contribute in vivo to local periodontal tissue destruction.

PMID- 12795794
TI  - Safety and efficiency of novel sonic scaler tips in vitro.
AB  - BACKGROUND: The aim of the study was to evaluate a novel sonic scaler tip for
      subgingival root surface instrumentation combining high efficiency in calculus
      removal with minimized risk of root damage through subgingival debridement.
      METHODS: A metal sonic scaler tip with a paddle-like working end covered with
      spheroid convexities of 0.8 mm diameter and 0.3 mm height was designed from the
      aspect of optimized adaptation to the root anatomy (tip-end dimension: 3.0 x 1.5
      x 0.6 mm). Using a customary sonic scaler tip as control, instrument efficiency
      was quantified by measuring the time needed to completely remove calculus on
      extracted teeth (n=52) under standardized conditions. To quantify the amount of
      calculus removed, the mean calculus area per tooth was measured on photographs
      taken before instrumentation. The tips safety was evaluated instrumenting
      calculus-free root surfaces in vitro (n=18, lateral forces 0.5, 1, 2 N, 20 s
      instrumentation time, tip angulation 0 degrees ) with subsequent laser-optical
      determination of resulting root substance loss. RESULTS: Debridement efficiency
      was significantly higher for the novel tip (0.78+/-0.81 mm2/s completely
      debrided) than for the conventional tip (0.42+/-0.33 mm2) (Mann-Whitney test,
      p<0.05). Concerning instrument safety, the novel tip caused significantly less
      root substance loss than the conventional tip. CONCLUSION: The novel scaler tip
      appears to be significantly more efficient in calculus removal and less damaging
      to the root surface than the assessed conventional tip.

PMID- 12795796
TI  - Five-year maintenance follow-up of early-onset periodontitis patients.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical and
      microbiological status of patients with early-onset or aggressive periodontitis
      (EOP) who had received supportive periodontal care (SPC) every 3-6 months for a
      period of 5 years, following active periodontal treatment. MATERIAL AND METHODS:
      The study population consisted of 25 individuals with early-onset periodontitis.
      Clinical examination and recordings of probing pocket depth (PPD) and clinical
      attachment level (CAL) were performed at baseline prior to treatment (T0), 3
      months following the termination of active periodontal treatment (T1) and
      annually at the SPC appointments (T2,T3,T4,T5). Microbiological samples were
      obtained at the 5-year SPC (T5). Subgingival plaque samples for each individual
      were collected from one deep pocket (>5 mm), based on pretreatment measurements,
      randomly selected in each quadrant. The levels of Actinobacillus
      actinomycetemcomitans, Bacteroides forsythus, Porphyromonas gingivalis and
      Treponema denticola were determined using oligonucleotide probe hybridization.
      RESULTS: During the 5-year period, the mean of SPC/patient was 12.7 sessions. A
      significant improvement was observed in PPD, CAL, gingival bleeding index and
      suppuration following treatment. However, between T1 and T5, 134 sites in 20
      patients deteriorated with a CAL loss of> or =2 mm. Out of these 134 sites
      showing disease progression, microbial samples were randomly obtained in 13 sites
      (9.7%) from 8 patients. Among other factors, smoking and stress were found to
      have significant predictive value on the future attachment loss. P. gingivalis,
      T. denticola and total bacterial load were statistically significantly higher in
      patients who experienced disease progression during the 5-year maintenance
      period. CONCLUSIONS: For most EOP patients, regular SPC was effective in
      maintaining clinical and microbiological improvements attained after active
      periodontal therapy. However, a small percentage of sites was identified as
      progressive in 20 patients. Variables found to be related to periodontal
      progression were the presence of as well as the high bacterial counts of P.
      gingivalis, T. denticola and total bacterial load, number of acute episodes,
      number of teeth lost, smoking and stress.

PMID- 12795795
TI  - Modulation of androgen metabolism by phenytoin, oestradiol and tamoxifen in human
      gingival fibroblasts.
AB  - OBJECTIVES: The aim of this investigation is to study androgen metabolism in
      gingival fibroblasts in response to phenytoin, oestradiol and the antioestrogen
      tamoxifen, in order to establish the possible role of hormones in the
      aetiopathogenesis of phenytoin-induced gingival overgrowth. MATERIALS AND
      METHODS: Six cell lines of human gingival fibroblasts were established in
      monolayer culture in Eagle's minimum essential medium. Duplicate incubations were
      performed independently with radiolabelled testosterone and 4-androstenedione,
      respectively (14C-T/14C-4-A), with optimal concentrations of phenytoin,
      oestradiol and tamoxifen alone and in combination. At the end of a 24-h
      incubation period, the medium was solvent extracted for steroid metabolites,
      which were separated by thin layer chromatography and quantified using a
      radioisotope scanner. RESULTS: The substrates were metabolised mainly to the
      diols, 5alpha-dihydrotestosterone (DHT) and 4-androstenedione or testosterone,
      with the two substrates used. The trends were that phenytoin and oestradiol
      significantly elevated the yields of the androgens DHT, diols and 4
      A/testosterone from both substrates while tamoxifen inhibited the stimulatory
      effects of oestradiol and phenytoin alone and in combination (n=6; p<0.01, one
      way anova). CONCLUSION: Specific hormone-mediated activity in response to
      phenytoin could contribute to the pathogenesis of gingival overgrowth, which can
      be decreased by the anti oestrogen tamoxifen.

PMID- 12795797
TI  - Efficacy of a 0.5% chlorhexidine gel on the control of gingivitis in Brazilian
      mentally handicapped patients.
AB  - OBJECTIVE: To evaluate the effectiveness of a 0.5% chlorhexidine gel on the
      reduction of interdental gingival bleeding. MATERIAL AND METHODS: Forty-three
      mentally handicapped subjects, living in an institution (Casas Andre Luiz,
      Brazil), were enrolled in a double-blind randomised clinical trial. The subjects
      were randomly divided into two groups: test (chlorhexidine gel) and control
      (placebo gel). The gel was applied with trays, twice a day, over a period of 8
      weeks. The interdental bleeding index (IBI) was recorded before and after the
      period in which the gel was used. RESULTS: Statistical analysis showed that
      baseline IBI scores were similar (p=0.82) for test and control groups (55.6% and
      54.5%, respectively). After 8 weeks, a statistically significant (p<0.001)
      decrease in IBI means took place in the test group (33.2%). The control group
      presented a small increase (60.6%) in IBI scores. The difference between groups
      was significant at the end of the study (p<0.001). CONCLUSION: The results
      indicated that the use of a 0.5% chlorhexidine gel was effective in reducing
      interdental gingival bleeding in special patients.

PMID- 12795798
TI  - Gene therapy for ovarian cancer: development of novel treatment strategies.
AB  - In the last decade, advances in molecular biology have lead to the development of
      techniques that permit the manipulation of mammalian cell DNA for diagnostic and
      therapeutic purposes. Gene therapy has subsequently evolved as a treatment option
      in patients with malignancies. In this article, we have summarized current
      strategies in gene therapy for ovarian cancer.

PMID- 12795799
TI  - FaFEC: a novel regimen for advanced ovarian cancer.
AB  - A palliative combination chemotherapy regimen (FaFEC) was developed for patients
      with relapsed epithelial ovarian cancer in particular patients relapsing after,
      or ineligible to enter, phase II trials, usually due to lack of evaluable
      disease. Forty-six patients were enrolled. Patients had received a mean of 2.3
      previous drug regimens and nine (19%) had intestinal obstruction at the start of
      FaFEC. The majority of patients were inevaluable by WHO criteria so objective
      response data was obtained from serial serum CA125 evaluations. A serological
      response was demonstrated in 8/44 (18%). The responders included 6/27 women who
      had a prior relapse-free interval of less than 3 months, four who were resistant
      to platinum chemotherapy and three patients who had previously received
      paclitaxel. The major (WHO grade 3/4) toxicities included leucopenia (six
      patients), anemia (three patients), thrombocytopenia (two patients), nausea and
      vomiting (four patients) and severe infections (five patients). Following FaFEC
      the median time to failure was 0.48 years and the median survival was 0.66 years.
      FaFEC was effective in this group of very poor prognosis patients. The
      serological response rate of 18% is noteworthy considering the multiple prior
      treatments that patients had received and the short treatment free intervals.
      FaFEC may be useful second line therapy in epithelial ovarian cancer patients
      ineligible for phase II studies and should be considered for a randomized
      comparison with paclitaxel.

PMID- 12795800
TI  - Systematic pelvic and para-aortic lymphadenectomy in advanced ovarian cancer
      patients with no residual intraperitoneal disease.
AB  - A comparative non-randomized study was carried out to evaluate the role of
      systematic pelvic and para-aortic lymphadenectomy (SL) on patients with no
      residual intraperitoneal disease (NRID) of advanced ovarian cancer (stage IIIC
      IV). A total of 142 optimally cytoreduced patients (macroscopic disease absent on
      peritoneal surface) were divided into two groups: Group A, consisting of 98
      patients (53 previously untreated and 45 pretreated at other Institutions), who
      underwent SL; Group B, consisting of 44 patients (21 previously untreated and 23
      pretreated at other Institutions), who did not undergo SL. Each group had
      statistically equivalent histology, grading, performance status and variety of
      cytoreductive operations performed. Group A pretreated patients had a greater
      number of stage III than Group B (P = 0.03). Systematic pelvic and para-aortic
      lymphadenectomy could be carried out with an acceptable morbidity and no
      mortality. All 142 patients received post-operative chemotherapy including
      carboplatin. The number of chemotherapy sessions did not differ between the two
      groups. Comparison of survival revealed that SL significantly improved the
      survival of previously untreated patients (P = 0.02). The survival was
      significantly different with nodal status (P = 0.006). Cox's proportional hazard
      analysis showed that only systematic lymphadenectomy was a significant covariate.
      The survival was not significantly different in Group A vs Group B pretreated
      patients; however, it was significantly different with respect to nodal status
      (P<0.001). Cox's proportional hazard analysis showed that only the initial stage
      of disease was a significant covariate. The results of the present study shows
      that aggressive surgical cytoreduction with SL could be therapeutic in previously
      untreated patients with NRID. Currently, an international prospective randomized
      study is ongoing to clarify definitively the clinical role of SL.

PMID- 12795801
TI  - Management of high-risk gestational trophoblastic disease--the Memorial Hospital
      experience.
AB  - Thirty-two patients with high-risk gestational trophoblastic disease (GTD),
      defined as metastases to the brain or liver (regardless of hCG level or duration
      of disease) or prior unsuccessful chemotherapy are reviewed. In this
      classification, an antecedent term pregnancy is not considered to be an
      independent high-risk factor. Initial chemotherapy in 15 (46.8%) patients
      consisted of methotrexate, actinomycin D, and chlorambucil (MAC), actinomycin D
      alone in seven (21.8%), etoposide, methotrexate, actinomycin D, cytoxan on covin
      (EMACO) EMACO in three (9.4%), ITMA (hydroxyurea, vincristine, methotrexate,
      folinic acid, cyclophosphamide, actinomycin D, adriamycin, and melphalan) in
      three (9.4%). The remaining patients were treated with actinomycin D and 6
      mercaptopurine (1), CHAMOCA (1), carboplatin and Taxol (1), and methotrexate (1).
      All patients with brain metastases were treated with cranial radiotherapy.
      Overall complete remission was achieved in 14 of 32 (43.7%) patients. Five of 9
      (55.5%) patients whose disease followed a term pregnancy survived compared to
      nine of 23 (39.1%) patients whose disease followed other types of pregnancies.
      The data analyzed according to the clinical classification of 'high-risk'
      indicates that an overall survival rate of 70% was achieved. The Memorial
      Hospital classification therefore identifies patients who need primary
      chemotherapy more aggressive than MAC and similar to the WHO scoring system is a
      better predictor of survival than the clinical classification.

PMID- 12795802
TI  - Prognostic importance of the nuclear proteins p53 and Rb in conjunction with DNA,
      nuclear morphometry and grading in endometrial carcinoma.
AB  - In a series of 227 cases of endometrial carcinomas in FIGO stages I-IV, treated
      during the years 1984-89, immunohistochemical staining for the protein products
      of the two tumor suppressor genes p53 and retinoblastoma (Rb) were evaluated as
      prognostic factors with regard to tumor stage, FIGO grade, nuclear grade,
      morphometric nuclear parameters, DNA ploidy and S-phase fraction. Long-term
      survival analyses were endpoints and the Cox multivariate technique was used to
      evaluate the prognostic factors. In 20% of the cases p53 was positive. This was a
      genuine high-risk group associated with primary advanced carcinoma,
      nonendometrioid histology, poorly differentiated tumors, severe nuclear atypia,
      DNA aneuploidy, primary persistent tumors, recurrent tumors and a poor long-term
      survival rate (37% 5-year survival). In patients dying of their disease, 54% of
      the tumors stained positive for p53, compared with only 10% of the tumors not
      killing their hosts. Positive p53 staining was more common in older women. A
      pathologic Rb status (negative staining) was recorded in 6% of the cases. The Rb
      factor had only a minor influence on long-term survival and was not significant
      in multivariate analyses. The p53 staining status was the second most important
      prognostic factor after the nuclear grade in Cox multivariate analyses, after
      correcting for stage and age. Immunohistochemical staining for p53 protein should
      be included among previous available and important prognostic factors in
      endometrial carcinoma.

PMID- 12795803
TI  - What should be the cut-off level of serum CA125 to evaluate the disease status
      before second-look laparotomy in epithelial ovarian carcinoma?
AB  - To assess the predictive value of serum CA125 level prior to second-look
      laparotomy in epithelial ovarian carcinoma, 45 patients who were clinically or
      radiologically tumor-free prior to a second-look laparotomy were studied. Serum
      CA125 levels were measured 10 days prior to the operation, and were compared with
      the surgico-pathological results. Twenty-eight (62%) patients were found to have
      tumor at surgery. The serum CA125 levels were > or = 35 U ml-1 (42%) patients.
      Tumors were found in 14 (74%) of these 19 patients. Although a serum CA125 level
      > or = 35 U ml-1 was a strong predictor of the presence of an intraperitoneal
      tumor, a level <35 U ml-1 was not predictive of a tumor-free state. When the cut
      off level was accepted as 20 U ml-1, 28 patients (62%) were found to have
      elevated CA125 level. The sensitivity, the specificity, the positive and negative
      predictive value and the false negative ratio were calculated as 79%, 65%, 79%,
      65% and 21% respectively. The threshold value for a raised CA125 level was
      considered and a lower level of 20 U ml-1 was suggested as a cut-off level prior
      to second-look laparotomy in evaluating patients with known epithelial ovarian
      cancer.

PMID- 12795804
TI  - Ovarian function after radical hysterectomy for carcinoma of the cervix.
AB  - We present a prospective observational study of ovarian function following
      Wertheim's hysterectomy and its relationship to age at hysterectomy. Serum
      gonadotrophin measurements were made annually on 55 women following Wertheim's
      hysterectomy with ovarian preservation. Within 1 year of surgery four women
      (4/54) had biochemical evidence of ovarian failure, three of whom were over the
      age of 40 at operation. At 2 years eight women (8/51) had ovarian failure, seven
      of these women were over the age of 40 at the time of surgery. After 4 years 11
      women had ovarian failure (11/34), eight of these were over the age of 40 at
      operation. Ovarian function following Wertheim's hysterectomy is well maintained
      in women under the age of 40 at the time of their surgery, 87% of these women had
      normal gonadotrophin levels 4 years after their surgery. For women over the age
      of 40 ovarian function is poorly maintained, with only 27% with normal
      gonadotrophins 4 years following surgery. These data suggest that we should
      carefully consider recommending bilateral oophorectomy at Wertheim's hysterectomy
      in women over the age of 40.

PMID- 12795805
TI  - The relevance of various vulvar epithelial changes in the early detection of
      squamous cell carcinoma of the vulva.
AB  - The objective of this study is to evaluate the possible relevance of vulvar
      epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The
      data of 66 women surgically treated for squamous cell carcinoma of the vulva have
      been analyzed. More than 6500 slides from the resection specimens were revised
      with special emphasis on concurrent epithelial changes. Synchronous epithelial
      changes were seen in 63 patients. Thirty-nine patients had synchronous vulvar
      intra-epithelial neoplasia grade 1 (VIN I), 10 VIN II and 13 VIN III. Thirty-one
      patients had synchronous lichen sclerosus and 49 squamous cell hyperplasia. The
      difference between the percentage of patients with epithelial changes diagnosed
      preceding their carcinoma (30%) and the percentage of patients that had
      synchronous epithelial changes after reviewing the specimen (95%) was striking.
      It was concluded that more careful diagnosis, treatment and follow-up of these
      conditions might lead to an earlier recognition of squamous cell carcinoma of the
      vulva and therefore to a better prognosis.

PMID- 12795806
TI  - Adult granulosa-cell tumor of the ovary: a retrospective study of 45 cases.
AB  - This study describes 45 cases of adult granulosa-cell tumors seen in our
      institution between 1976 and 1993. The median age was 46.5 years (12-77) and 18
      women were postmenopausal. Vaginal bleeding was present in one-third of cases;
      other complaints were abdominal pain (28%) and the presence of a pelvic mass
      (47%). The tumor size was variable (<3 cm to 30 cm, median 11.5 cm). FIGO stages
      were: stage I: 30 (73%) (19 Ia, seven Ic, four I unknown); stage II: seven (17%)
      (two IIa, five IIC); stage III: three (7%) (one IIIb, two IIIc). Two
      adenocarcinomas and 13 cases of hyperplasia were found in 25 endometrial samples
      available. The initial therapy for all the cases was surgery, consisting in 34
      patients of hysterectomy, bilateral salpingo-oophorectomy, +/- tumor resection.
      Sixteen patients received adjuvant therapy as well: chemotherapy (CT) alone for
      12, radiotherapy (RT) alone for two, and CT + RT for two patients. Among the 39
      patients who achieved a complete response after initial therapy, 15 patients have
      relapsed (pelvic recurrences) (38.5%) including six stage Ia (three received only
      conservative surgery). All the recurrent tumors were resected and 14/15 had CT
      (13/14 with cisplatin). The overall survival rate was 77.2% at 5 years, 66.5% at
      10 years, and 41.2% at 20 years. A statistically significant difference was found
      between the survival of patients with stage Ia disease (75% at 10 and 15 years)
      and that of other patients (60% at 10 years, and <50% at 15 years). Serum
      estradiol and serum inhibin were measured in some patients and the results are
      described.

PMID- 12795807
TI  - Choriocarcinoma coexistent with intrauterine pregnancy: two additional cases and
      a review of the literature.
AB  - Choriocarcinoma coexistent with normal intrauterine pregnancy is rare and poses
      questions about its origin. Although the development from trophoblastic remnants
      of previous pregnancies can not be excluded in some cases, the findings of
      incidental macro- and microscopic foci of choriocarcinoma in apparently normal
      placentas show the possible transformation of normal trophoblast into
      choriocarcinoma during an otherwise normal pregnancy. The diagnosis and
      management of choriocarcinoma coexistent with intrauterine pregnancy have changed
      dramatically over the decades but the survival rates are still unsatisfactory. In
      this review, we summarize some of the most common features of this disease.

PMID- 12795808
TI  - Serum CA125 assay at the time of relapse has no prognostic relevance in patients
      undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian
      study.
AB  - The present retrospective study assessed the prognostic value of serum CA125
      assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the
      time of relapse, serum CA125 levels ranged from 7 to 7000 U ml-1. The 25%, 50%
      and 75% quantiles of CA125 levels were 76, 178 and 339 U ml-1, respectively.
      Antigen values were >35 U ml-1 in 67 (91.8%) of the 73 patients. Median time to
      recurrence was 16 months (range, 4-62 months). Serum CA125 levels at relapse were
      not related to site of recurrence, time to recurrence, FIGO stage, histologic
      type, tumor grade and residual disease after initial surgery. Sixty patients
      received salvage chemotherapy at relapse. In these patients survival after
      recurrence was significantly related to time to recurrence (< or = 6 months vs <
      6 months, P = 0.0371; < or =12 months vs >12 months, P = 0.0014; < or =16 months
      vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off
      value for the antigen: 35, 76, 178 and 339 U ml-1), site of recurrence, FIGO
      stage, histologic type, tumor grade and residual disease after initial surgery.
      In conclusion, time to recurrence was the only variable predictive of further
      survival in patients undergoing salvage chemotherapy for recurrent ovarian
      cancer, whereas serum CA125 level at relapse had no prognostic relevance.

PMID- 12795809
TI  - Extramammary Paget's disease with diffuse involvement of the lower female genito
      urinary system.
AB  - Extramammary Paget's disease of the lower female genito-urinary system is an
      uncommon neoplasm with a high rate of recurrence. A 52-year-old white female with
      a history of extramammary Paget's disease, originally excised in 1985 by skinning
      vulvectomy and who had multiple recurrences, including two in a vaginal graft and
      with extension to the urethra and the uterine cervix, in 1992 underwent an
      anterior pelvic exenteration for control of the disease process. Standard
      surgical management for extramammary Paget's disease without invasion or without
      an underlying adenocarcinoma is simple or skinning vulvectomy. However, because
      the disease commonly recurs, diffuse involvement may require more extensive
      surgery including pelvic exenteration in extraordinary cases.

PMID- 12795810
TI  - Adrenalectomy stimulates hypothalamic proopiomelanocortin expression but does not
      correct diet-induced obesity.
AB  - BACKGROUND: Elevated glucocorticoid production and reduced hypothalamic POMC mRNA
      can cause obese phenotypes. Conversely, adrenalectomy can reverse obese
      phenotypes caused by the absence of leptin, a model in which glucocorticoid
      production is elevated. Adrenalectomy also increases hypothalamic POMC mRNA in
      leptin-deficient mice. However most forms of human obesity do not appear to
      entail elevated plasma glucocorticoids. It is therefore not clear if reducing
      glucocorticoid production would be useful to treat these forms of obesity. We
      hypothesized that adrenalectomy would increase hypothalamic POMC mRNA and reverse
      obese phenotypes in obesity due to a high-fat diet as it does in obesity due to
      leptin deficiency. RESULTS: Retired breeder male mice were placed on a high-fat
      diet or a low-fat diet for two weeks, then adrenalectomized or sham
      adrenalectomized. The high-fat diet increased body weight, adiposity, and plasma
      leptin, led to impaired glucose tolerance, and slightly stimulated hypothalamic
      proopiomelanocortin (POMC) expression. Adrenalectomy of mice on the high-fat diet
      significantly reduced plasma corticosterone and strikingly increased both
      pituitary and hypothalamic POMC mRNA, but failed to reduce body weight, adiposity
      or leptin, although slight improvements in glucose tolerance and metabolic rate
      were observed. CONCLUSION: These data suggest that neither reduction of plasma
      glucocorticoid levels nor elevation of hypothalamic POMC expression is effective
      to significantly reverse diet-induced obesity.

PMID- 12795811
TI  - Seasonal changes, sleep length and circadian preference among twins with bipolar
      disorder.
AB  - BACKGROUND: We aimed at studying the seasonal changes in mood and behaviour, the
      distribution of hospital admissions by season, and the persistence of the
      circadian type in twins with bipolar disorder and their healthy co-twins.
      METHODS: All Finnish like-sex twins born from 1940 to 1969 were screened for a
      diagnosis of bipolar type I disorder. The diagnosis was assessed with a
      structured research interview, and the study subjects (n = 67) filled in the
      Seasonal Pattern Assessment Questionnaire (SPAQ) and the Morningness-Eveningness
      Questionnaire (MEQ). For studying the persistence of the habitual sleep length
      and circadian type, we used data derived from the Finnish Twin Cohort
      Questionnaire (FTCQ). Bipolar twins were compared with their healthy co-twins.
      RESULTS: Bipolar twins had greater seasonal changes in sleep length (p = 0.01)
      and mood (p = 0.01), and higher global seasonality scores (p = 0.03) as compared
      with their co-twins with no mental disorder. Sunny days (p = 0.03) had a greater
      positive effect on wellbeing in the bipolar than healthy co-twins. CONCLUSIONS:
      Our results support the view that bipolar disorder is sensitive to the
      environmental influence in general and to the seasonal effect in specific.
      Exposure to natural light appears to have a substantial effect on wellbeing in
      twins with bipolar disorder.

PMID- 12795812
TI  - Twice-daily amprenavir 1200 mg versus amprenavir 600 mg/ritonavir 100 mg, in
      combination with at least 2 other antiretroviral drugs, in HIV-1-infected
      patients.
AB  - BACKGROUND: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure.
      Little has been published on the efficacy, tolerability, and safety of APV 600
      mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID
      (APV1200). METHODS: ESS40011 was a 24-week, multicenter, open-label, clinical
      trial in which antiretroviral therapy-naive and -experienced HIV-1-infected
      adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in
      combination with > or = 2 non-protease inhibitor antiretroviral drugs. Non
      inferiority of the APV600/RTV regimen to the APV1200 regimen was established if
      the 95% lower confidence limit for the difference in proportion of patients
      achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was
      > or =-0.12. Late in the conduct of the trial, patients not yet completing 24
      weeks of therapy were given the option of continuing treatment for an additional
      24-week period. RESULTS: 211 patients were randomized, 158 to APV600/RTV and 53
      to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1
      RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat:
      observed analysis). In the APV600/RTV arm, significantly more patients achieved
      HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and
      greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59
      log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to
      mean overall change from baseline in CD4+ count, frequency of drug-related grade
      1-4 adverse events, and frequency of discontinuing treatment due to adverse
      events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although
      a lower proportion of patients in the APV600/RTV arm experienced drug-related
      oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1
      RNA <200 copies/mL at week 24 and chose to continue study treatment maintained
      this level of virologic suppression at follow-up 24 weeks later. CONCLUSIONS:
      APV600 RTV BID was similar to or better than APV1200 BID in virologic response.
      Virologic results in a small number of patients who continued treatment for 24
      weeks post-study suggest that virologic suppression with APV600 RTV BID is
      durable.

PMID- 12795814
TI  - Esophageal and small bowel obstruction by occupational bezoar: report of a case.
AB  - BACKGROUND: Phytobezoar may be a cause of bowel obstruction in patients with
      previous gastric surgery. Most bezoars are concretions of poorly digested food,
      which are usually formed initially in the stomach. Intestinal obstruction
      (esophageal and small bowel) caused by an occupational bezoar has not been
      reported. CASE PRESENTATION: A 70-year old male is presented suffering from
      esophageal and small bowel obstruction, caused by an occupational bezoar. The
      patient has worked as a carpenter for 35 years. He had undergone a vagotomy and
      pyloroplasty 10 years earlier. The part of the bezoar, which caused the
      esophageal obstruction was removed during endoscopy, while the part of the small
      bowel was treated surgically. The patient recovered well and was discharged on
      the 8th postoperative day. CONCLUSIONS: Since occupational bezoars may be a cause
      of intestinal obstruction (esophageal and/or small bowel), patients who have
      undergone a previous gastric surgery should avoid occupational exposures similar
      to the presented case.

PMID- 12795813
TI  - Differential gene expression in the murine gastric fundus lacking interstitial
      cells of Cajal.
AB  - BACKGROUND: The muscle layers of murine gastric fundus have no interstitial cells
      of Cajal at the level of the myenteric plexus and only possess intramuscular
      interstitial cells and this tissue does not generate electric slow waves. The
      absence of intramuscular interstitial cells in W/WV mutants provides a unique
      opportunity to study the molecular changes that are associated with the loss of
      these intercalating cells. METHOD: The gene expression profile of the gastric
      fundus of wild type and W/WV mice was assayed by murine microarray analysis
      displaying a total of 8734 elements. Queried genes from the microarray analysis
      were confirmed by semi-quantitative reverse transcription-polymerase chain
      reaction. RESULTS: Twenty-one genes were differentially expressed in wild type
      and W/WV mice. Eleven transcripts had 2.0-2.5 fold higher mRNA expression in W/WV
      gastric fundus when compared to wild type tissues. Ten transcripts had 2.1-3.9
      fold lower expression in W/WV mutants in comparison with wild type animals. None
      of these genes have ever been implicated in any bowel motility function.
      CONCLUSIONS: These data provides evidence that several important genes have
      significantly changed in the murine fundus of W/WV mutants that lack
      intramuscular interstitial cells of Cajal and have reduced enteric motor
      neurotransmission.

PMID- 12795815
TI  - Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) interact with heterotrimeric GTP
      binding proteins (G proteins) to modulate acute changes in intracellular
      messenger levels and ion channel activity. In contrast, long-term changes in
      cellular growth, proliferation and differentiation are often mediated by tyrosine
      kinase receptors and certain GPCRs by activation of mitogen-activated protein
      (MAP) kinases. Complex interactions occur between these signaling pathways, but
      the specific mechanisms of such regulatory events are not well-understood. In
      particular it is not clear whether GPCRs are modulated by tyrosine kinase
      receptor-MAP kinase pathways. RESULTS: Here we describe tyrosine kinase receptor
      regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT2C
      receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK)
      inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and
      insulin-like growth factor type 1 (IGF-1) on the 5-HT2C receptor is dependent on
      tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin
      had no effect on another GPCR that shares the same G protein signaling pathway as
      the 5-HT2C receptor. This effect is also direct: activated MAP kinase mimicked
      the effect of insulin, and removing a putative MAP kinase site from the 5-HT2C
      receptor abolished the effect of insulin. CONCLUSION: These results show that
      insulin signaling can inhibit 5-HT2C receptor activity and suggest that MAP
      kinase may play a direct role in regulating the function of a specific GPCR.

PMID- 12795816
TI  - Phenotypic mixing and hiding may contribute to memory in viral quasispecies.
AB  - BACKGROUND: In a number of recent experiments with food-and-mouth disease virus,
      a deleterious mutant, RED, was found to avoid extinction and remain in the
      population for long periods of time. Since RED characterizes the past
      evolutionary history of the population, this observation was called quasispecies
      memory. While the quasispecies theory predicts the existence of these memory
      genomes, there is a disagreement between the expected and observed mutant
      frequency values. Therefore, the origin of quasispecies memory is not fully
      understood. RESULTS: We propose and analyze a simple model of complementation
      between the wild type virus and a mutant that has an impaired ability of cell
      entry, the likely cause of fitness differences between wild type and RED mutants.
      The mutant will go extinct unless it is recreated from the wild type through
      mutations. However, under phenotypic mixing-and-hiding as a mechanism of
      complementation, the time to extinction in the absence of mutations increases
      with increasing multiplicity of infection (m.o.i.). If the RED mutant is
      constantly recreated by mutations, then its frequency at equilibrium under
      selection-mutation balance also increases with increasing m.o.i. At high m.o.i.,
      a large fraction of mutant genomes are encapsidated with wild-type protein, which
      enables them to infect cells as efficiently as the wild type virions, and thus
      increases their fitness to the wild-type level. Moreover, even at low m.o.i. the
      equilibrium frequency of the mutant is higher than predicted by the standard
      quasispecies model, because a fraction of mutant virions generated from wild-type
      parents will also be encapsidated by wild-type protein. CONCLUSIONS: Our model
      predicts that phenotypic hiding will strongly influence the population dynamics
      of viruses, particularly at high m.o.i., and will also have important effects on
      the mutation-selection balance at low m.o.i. The delay in mutant extinction and
      increase in mutant frequencies at equilibrium may, at least in part, explain
      memory in quasispecies populations.

PMID- 12795818
TI  - FAO/WHO launch expert report on diet, nutrition and prevention of chronic
      diseases.

PMID- 12795817
TI  - A data review and re-assessment of ovarian cancer serum proteomic profiling.
AB  - BACKGROUND: The early detection of ovarian cancer has the potential to
      dramatically reduce mortality. Recently, the use of mass spectrometry to develop
      profiles of patient serum proteins, combined with advanced data mining algorithms
      has been reported as a promising method to achieve this goal. In this report, we
      analyze the Ovarian Dataset 8-7-02 downloaded from the Clinical Proteomics
      Program Databank website, using nonparametric statistics and stepwise
      discriminant analysis to develop rules to diagnose patients, as well as to
      understand general patterns in the data that may guide future research. RESULTS:
      The mass spectrometry serum profiles derived from cancer and controls exhibited
      numerous statistical differences. For example, use of the Wilcoxon test in
      comparing the intensity at each of the 15,154 mass to charge (M/Z) values between
      the cancer and controls, resulted in the detection of 3,591 M/Z values whose
      intensities differed by a p-value of 10-6 or less. The region containing the M/Z
      values of greatest statistical difference between cancer and controls occurred at
      M/Z values less than 500. For example the M/Z values of 2.7921478 and 245.53704
      could be used to significantly separate the cancer from control groups. Three
      other sets of M/Z values were developed using a training set that could
      distinguish between cancer and control subjects in a test set with 100%
      sensitivity and specificity. CONCLUSION: The ability to discriminate between
      cancer and control subjects based on the M/Z values of 2.7921478 and 245.53704
      reveals the existence of a significant non-biologic experimental bias between
      these two groups. This bias may invalidate attempts to use this dataset to find
      patterns of reproducible diagnostic value. To minimize false discovery, results
      using mass spectrometry and data mining algorithms should be carefully reviewed
      and benchmarked with routine statistical methods.

PMID- 12795819
TI  - Out of the box.

PMID- 12795820
TI  - The prevalences of overweight and obesity in children aged 4 to 12 years in
      Gibraltar.
AB  - OBJECTIVE: To determine the prevalences of overweight and obesity in children
      aged 4 to 12 years, using the standard definitions proposed by the International
      Obesity Taskforce. DESIGN: Population prevalence cross-sectional survey involving
      measurement of height and weight. Data collection took place in 1998. SETTING:
      Schools in Gibraltar. SUBJECTS: In total 2994 children, aged 4-12 years,
      attending these schools (1540 boys, 1454 girls). RESULTS: Prevalence of
      overweight in boys was 19.7%, while obesity prevalence was 10.8%. For the girls,
      overweight prevalence was 21.4%, while obesity prevalence was 10.6%. There were
      no significant differences in the proportions of overweight or obesity between
      boys and girls. CONCLUSIONS: This was the first time that the prevalences of
      overweight and obesity have been estimated in children from Gibraltar. These data
      provide further information on prevalence rates of overweight and obesity, using
      defined cut-offs for comparison with data from other countries.

PMID- 12795821
TI  - Yoghurt in the Spanish diet: nutritional implications and socio-cultural aspects
      of its consumption.
AB  - OBJECTIVES: This study aims to analyse the differences, with regard to socio
      cultural characteristics and dietary habits, between low and high consumers of
      yoghurt and other fermented dairy product desserts, and the nutritional
      significance of these differences. METHODS: We analysed the diet of a healthy
      population (4-65 years), using the 24-hour recall method, on three non
      consecutive days. The participants were grouped by age and sex and were also
      divided into tertiles on the basis of yoghurt consumption. We compared energy and
      nutrient intakes, educational level and socio-economic status in the low
      consumption (LC) group and the high consumption (HC) group. RESULTS: In general
      there were no significant differences in energy intake or nutritional profile
      between LC and HC groups. The only significant difference was in the percentage
      of energy provided by lipids, which was significantly lower in HC women, possibly
      due to the high number of women in this group who consumed low-fat yoghurt. There
      were significant differences in the distribution of HC and LC subjects according
      to the three educational levels but not according to socio-economic status.
      CONCLUSION: The fact of being a high consumer of fermented dairy products took
      place in the framework of other dietary changes that compensated for this high
      consumption, resulting in the absence of significant differences in energy intake
      and nutritional profile between HC and LC subjects. The only exception was found
      in women who consumed low-fat dairy products. There was a relationship between
      high consumption of fermented dairy products and educational level.

PMID- 12795823
TI  - Impact of ready-to-eat breakfast cereal (RTEBC) consumption on adequacy of
      micronutrient intakes and compliance with dietary recommendations in Irish
      adults.
AB  - OBJECTIVE: To describe the consumption of ready-to-eat-breakfast cereals (RTEBCs)
      in Irish adults and its impact on adequacy and safety of micronutrient intakes
      and compliance with dietary recommendations. DESIGN: Analysis for this paper used
      data from the North/South Ireland Food Consumption Survey that estimated habitual
      food intake using a 7-day food diary in a representative sample of adults aged 18
      64 years ( 662 men, 717 women). RESULTS: Despite the small quantity consumed
      (mean 28.6 g day-1 or 4.7% of total energy intake), RTEBCs made an important
      contribution to the mean daily intake of carbohydrate (8.1%), starch (10.8%),
      dietary fibre (9.8%) and non-starch polysaccharides (NSP) (10.8%) in consumers.
      Increased consumption was associated with a more fibre-dense diet and with
      greater compliance with dietary recommendations for fat, carbohydrate and NSP.
      Fortified RTEBCs contributed significantly to mean daily intakes of iron (18%),
      thiamin (14%), riboflavin (17%), niacin (15%), vitamin B6 (13%), total folate
      (18%) and vitamin D (10%) and most of the contribution was from micronutrients
      added to RTEBCs. Increased consumption of fortified RTEBCs was associated with an
      increased nutrient density for a number of micronutrients and with a lower
      prevalence of dietary inadequacy of calcium, iron, riboflavin and folate,
      particularly in women. However, it was not associated with intakes in excess of
      the Tolerable Upper Intake Level for any micronutrient. CONCLUSIONS: The
      consumption of RTEBCs is associated with improved compliance with dietary
      recommendations for fat, carbohydrate and fibre, with a more micronutrient-dense
      diet and a reduced risk of dietary inadequacy for calcium, iron, riboflavin and
      folate, without increasing the risk of excessive intakes of micronutrients.

PMID- 12795822
TI  - The association between red and processed meat consumption and iron intakes and
      status among British adults.
AB  - OBJECTIVE: To examine the association between consumption of red and processed
      meat (RPM) and iron intakes and status in adults. DESIGN: Further analysis of the
      Dietary and Nutritional Survey of British Adults, a cross-sectional study of 2197
      adults aged 16-64 years carried out in 1986/7. SUBJECTS AND METHODS: Adults (836
      men and 838 women) with serum ferritin measurements, who were not taking iron
      supplements, were classified into four groups according to RPM consumption (from
      7-day weighed records). Iron absorbed was estimated from equations based on haem
      and non-haem iron and the influence of iron stores. RESULTS: Women who ate least
      meat (<90 g day-1) had three times the risk of a low iron intake (below the Lower
      Reference Nutrient Intake) compared with high consumers of RPM (>140 g day-1).
      Men who ate no RPM also had a higher risk of low iron intake. Using an estimate
      of minimal values for iron losses, there was a twofold difference in the
      potential risk of negative iron balance between women non-RPM consumers and high
      RPM consumers. Status measurements indicated that, among women, anaemia was least
      prevalent (6%) among high consumers compared with 12-14% among average RPM
      consumers. Inverse trends were also observed for serum ferritin in both sexes.
      CONCLUSIONS: Low consumption of RPM has implications for iron intakes and iron
      status in men and women, since the risk of negative iron balance and its
      consequences are increased. Dietary messages must consider these implications and
      provide appropriate advice.

PMID- 12795824
TI  - Meal patterns and food use in 10- to 11-year-old Finnish children.
AB  - OBJECTIVE: To describe the meal patterns and food use on weekdays among 10- to 11
      year-old Finnish children and to analyse these in relation to family's socio
      economic status and the child's behaviour. DESIGN: Cross-sectional study on a
      cohort of 404 children aged 10-11 years in the rural town of Ylivieska, mid
      western Finland. METHODS: A food-frequency questionnaire including questions on
      meal patterns and food use and the Child Behaviour Checklist (CBCL) completed by
      the parents and the child together. RESULTS: Practically all children (99%) ate
      breakfast regularly, 94% had a daily school lunch and 80% had dinner at home
      daily. Vegetables were consumed daily at home by 26% and fruits or berries by
      21%, while 46% of the children had salad daily at school. Twenty-four per cent
      ate sweets daily or nearly so on weekdays. The children from families of high
      socio-economic status ate vegetables more often, and fewer of them used butter or
      high-fat milk. The children with no regular family dinner ate sweets and fast
      foods more often, and had higher total CBCL problem scores than those with a
      regular family dinner. CONCLUSION: Skipping meals appears not to be common among
      Finnish children aged 10-11 years, but a considerable proportion consume sweets
      frequently and vegetables infrequently. High family socio-economic status and a
      tendency to eat together are associated with healthy food choices among
      schoolchildren.

PMID- 12795825
TI  - Using different physical activity measurements in eight European countries.
      Results of the European Physical Activity Surveillance System (EUPASS) time
      series survey.
AB  - OBJECTIVES: The European Physical Activity Surveillance System (EUPASS) research
      project compared several physical activity (PA) measures (including the
      International Physical Activity Questionnaire (IPAQ)) in a time series survey in
      eight countries of the European Union. The present paper describes first results
      provided by the different instruments regarding PA participation, frequency and
      duration, both at the European and national levels. The purpose of the present
      study is to explore and compare the specific quality and usefulness of different
      indicators rather than to provide valid and reliable prevalence data. Thus, the
      main focus is on discussion of the methodological implications of the results
      presented. METHODS: A time series survey based on computer-aided telephone
      interviewing (CATI) was carried out in eight European countries over a six-month
      period. The study provided for about 100 realised interviews per month in each
      country (i.e. approximately 600 per country). Descriptive statistical analysis
      was used to: (1) report IPAQ results on vigorous, moderate and light PA and
      sitting, as well as on the overall measure of calories expenditure (MET min-1),
      in the different countries; (2) compare these results with national PA indicators
      tested in EUPASS; and (3) compare IPAQ results with other European studies.
      RESULTS: First, the scores for the different PA categories as well as for the
      overall measure of calories expenditure provided by the IPAQ appeared rather high
      compared with previous studies and public health recommendations. Second, the
      different PA measurements used in EUPASS provided completely different results.
      For example, national indicators used in Germany and The Netherlands to date
      neither corresponded in absolute values (e.g. means of PA or sitting) nor
      correlated with the IPAQ in any significant way. Third, comparing EU countries,
      the ranking for vigorous, moderate and light activities by use of the IPAQ
      differed from that of other European studies. For example, in the present
      analysis, German respondents generally showed higher scores for PA than the Finns
      and the Dutch, while, in contrast, findings from other studies ranked Finland
      before The Netherlands and Germany. CONCLUSIONS: The present analysis highlights
      some methodological implications of the IPAQ instrument. Among other things,
      differences in overall scores for PA as well as in the ranking of nations between
      the present results using IPAQ and other measures and studies may partly be due
      to the concepts of PA behind the measurements. Further analysis should
      investigate if the range of PA-related categories provided by the IPAQ is fully
      appropriate to measure all relevant daily activities; it may also consider the
      public health implications of mixing up different contexts of PA (e.g. work,
      leisure-time, transportation) in the IPAQ short version.

PMID- 12795826
TI  - Physical activity monitoring in Europe. The European Physical Activity
      Surveillance System (EUPASS) approach and indicator testing.
AB  - OBJECTIVES: The main objective of this paper is to describe the approach and
      specific findings of the European Physical Activity Surveillance System (EUPASS)
      research project. In particular, the analysis presented aims at testing the
      reliability, comparability and predictive power of different sets of physical
      activity (PA) indicators. DESIGN: First, a panel study based on computer-aided
      telephone interview (CATI) was designed to report PA data of a representative,
      selected group of about 100 persons per country at three points in time. Second,
      a CATI time series survey was carried out with the goal of realising about 100
      interviews per month over six consecutive months. SETTING: The project was
      carried out in eight European countries to support the development of the
      European Union's (EU) Health Monitoring Programme. SUBJECTS: Random population
      samples (subjects aged 18 years and older) were drawn from each participating
      country. RESULTS: While many PA indicators used in EU countries to date as well
      as the psychosocial and environmental measures tested in the present study had
      acceptable to good reliability coefficients, the test-retest reliability scores
      of the International Physical Activity Questionnaire (IPAQ) version tested (the
      short (last 7 days) telephone interview IPAQ; IPAQ-S7T) were rather low. The
      comparability between extant national PA items and the IPAQ-S7T was low for all
      countries. The strongest predictors of perceived health were the psychosocial and
      environmental PA indicators. CONCLUSIONS: According to the results of the present
      study, more research is needed to further investigate and improve the quality of
      the IPAQ. In addition, the specific predictive power of the tested psychosocial
      and environmental PA indicators on perceived health should be of particular
      interest for designing health surveillance activities in the future.

PMID- 12795827
TI  - Seasonal misclassification error and magnitude of true between-person variation
      in dietary nutrient intake: a random coefficients analysis and implications for
      the Japan Public Health Center (JPHC) Cohort Study.
AB  - OBJECTIVE: We examine (1) the extent to which seasonal diet assessments correctly
      classify individuals with respect to their usual nutrient intake, and (2) whether
      the magnitude of true variation in intake between individuals is seasonal. These
      effects could lead, respectively, to bias in estimates of relative risk for
      associations between usual nutrient exposure and disease, and to an increase in
      required sample size. SUBJECTS AND SETTING: One hundred and twenty-seven families
      in four regions of the Japan Public Health Center (JPHC) Cohort Study. DESIGN: On
      average, 48 weighed daily food records were collected per family over six seasons
      of 1994 and 1995. RESULTS: A random slopes regression model was used to predict
      the correlation between seasonal and annual average intakes, and to estimate true
      between-person variation in intakes by season. Mean vitamin C intake was greatest
      in summer and autumn, and seasonal variation was attributable to the consumption
      of fruit and vegetables. Predicted correlations between seasonal and annual
      average vitamin C intake ranged from 0.62 to 0.87, with greatest correlations in
      summer and autumn. True between-person variation in vitamin C intake was also
      strongly seasonal, ranging from 45 to 78% of total variance, and was again
      greatest in summer and autumn. These effects were less seasonal among energy and
      13 other nutrients. CONCLUSIONS: It may be possible substantially to reduce both
      seasonal misclassification of individuals with respect to their usual vitamin C
      intake, and required sample size, by asking subjects to report high-season intake
      of fruit and vegetables in the JPHC Study.

PMID- 12795828
TI  - Misclassification associated with measurement error in the assessment of dietary
      intake.
AB  - OBJECTIVE: Dietary assessment has been used for certification to receive food
      supplements or other nutrition services and to provide feedback for educational
      purposes. The proportion of individuals correctly certified as eligible is a
      function of the amount of error that exists in the dietary measures and the level
      of dietary intake used to establish eligibility. Whether individuals are
      correctly counselled to increase or decrease the consumption of selected foods or
      nutrients is a function of the same factors. It is not clear, however, what
      percentage of individuals would be correctly classified under what circumstances.
      The objective of this study is to demonstrate the extent to which measurement
      error and eligibility criteria affect the accuracy of classification. DESIGN:
      Hypothetical distributions of dietary intake were generated with varying degrees
      of measurement error. Different eligibility criteria were applied and the
      expected classification rates were determined using numerical methods. SETTING
      AND SUBJECTS: Simulation study. RESULTS: Cut points of dietary intake at
      decreasing levels below the 50th percentile of true intake were associated with
      lower sensitivity and predictive value positive rates, but higher specificity and
      predictive value negative rates. The correct classification rates were lower when
      two cut points of dietary intake were used. Using a single cut point that was
      higher than the targeted true consumption resulted in higher sensitivity but
      lower predictive value positive, and lower specificity but higher predictive
      value negative. CONCLUSIONS: Current methods of dietary assessment may not be
      reliable enough to attain acceptable levels of correct classification. Policy
      makers and educators must consider how much misclassification error they are
      willing to accept and determine whether more intensive methods are necessary.

PMID- 12795829
TI  - Adaptation of international nutrition databases and data-entry system tools to a
      specific population.
AB  - OBJECTIVE: To develop a nutritional dietary intake database based on available
      reliable international nutritional databases adapted to the local needs of a
      specific population. DESIGN: The Negev Nutritional Study (NNS) is a survey of a
      random sample of the Negev population regarding their dietary intake using 24
      hour dietary recalls. A nutritional database for the Israeli population was
      developed based on adaptation and modification of the US Department of
      Agriculture's database. A data-entry system was developed based on the logic of
      the US Food Information Analysis System. The system was designed as bilingual
      (English and Hebrew). Local foods and recipes were collected during the NNS,
      which included 1465 24-hour diet interviews. RESULTS: During the course of the
      NNS, 383 basic Israeli recipes were constructed. In total 1362 Israeli products
      were added to the database, and each was given a code, specific gravity and
      portion size. Most of the added products were cereals and grains and dairy
      products. The added recipes were collected from the interviewees in the NNS and
      from the most popular cookbooks. CONCLUSIONS: This paper describes the process
      undertaken to develop an Israeli food composition database as well as the data
      entry system. This knowledge may aid other research groups in developing a
      computerised, nation-specific nutritional database and data-entry system adapted
      to their own specific local needs.

PMID- 12795830
TI  - Validity and repeatability of a simple index derived from the short physical
      activity questionnaire used in the European Prospective Investigation into Cancer
      and Nutrition (EPIC) study.
AB  - OBJECTIVE: To assess the validity and repeatability of a simple index designed to
      rank participants according to their energy expenditure estimated by self-report,
      by comparison with objectively measured energy expenditure assessed by heart-rate
      monitoring with individual calibration. DESIGN: Energy expenditure was assessed
      over one year by four separate episodes of 4-day heart-rate monitoring, a method
      previously validated against whole-body calorimetry and doubly labelled water.
      Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum
      oxygen uptake. At the end of the 12-month period, participants completed a
      physical activity questionnaire that assessed past-year activity. A simple four
      level physical activity index was derived by combining occupational physical
      activity together with time participating in cycling and other physical exercise
      (such as keep fit, aerobics, swimming and jogging). SUBJECTS: One hundred and
      seventy-three randomly selected men and women aged 40 to 65 years. RESULTS: The
      repeatability of the physical activity index was high (weighted kappa=0.6, ).
      There were positive associations between the physical activity index from the
      questionnaire and the objective measures of the ratio of daytime energy
      expenditure to resting metabolic rate and cardio-respiratory fitness As an
      indirect test of validity, there was a positive association between the physical
      activity index and the ratio of energy intake, assessed by 7-day food diaries, to
      predicted basal metabolic rate. CONCLUSIONS: The summary index of physical
      activity derived from the questions used in the European Prospective
      Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for
      ranking participants in terms of their physical activity in large epidemiological
      studies. The index is simple and easy to comprehend, which may make it suitable
      for situations that require a concise, global index of activity.

PMID- 12795831
TI  - Comparison of an Australian food-frequency questionnaire with diet records:
      implications for nutrition surveillance.
AB  - OBJECTIVES: To compare a widely used Australian food-frequency questionnaire
      (FFQ) with diet records and consider the results in relation to its use in
      nutrition surveillance. DESIGN: Inter-method reliability study. SETTING: A
      randomised trial in subjects with past asbestos exposure. SUBJECTS: Seventy-two
      adults living in Western Australia. METHODS: A semi-quantitative FFQ developed by
      the Commonwealth Scientific Industrial Research Organisation in South Australia
      was administered after the completion of four 7-day diet records (DRs). RESULTS:
      Mean agreement between methods was not significantly different from 100% for many
      nutrients, but the limits of agreement indicated that, at the individual level,
      the FFQ over- or underestimated the DR by at least 50%. Mean agreement between
      methods decreased significantly with increasing intakes for the majority of
      nutrients. Pearson's correlation coefficients were less informative indicators of
      agreement compared with the limits of agreement. CONCLUSIONS: These results
      indicate poor agreement between the FFQ and DR when estimating absolute intakes.
      Therefore, comparing intakes collected using this FFQ with specific cut-off
      points such as Recommended Dietary Intakes for nutrition surveillance may lead to
      seriously flawed conclusions about population intakes.

PMID- 12795832
TI  - [Bio-panning of antagonistic peptides against HAb18G/CD147 and their function of
      anti-hepatoma invasion].
AB  - OBJECTIVE: To screen out the HAb18G/CD147 binding peptides and find out an
      antagonist against hepatoma invasion. METHODS: HAb18G/CD147 was purified by
      affinity chromatographic method and the antigen binding peptides acquired by bio
      panning a phage-displayed 12-peptide library. After obtaining the sequence of the
      selected phage-displayed peptides, all the 9 peptides were synthesized by solid
      phase method and identified by mass spectrograph. The peptides' anti-metastatic
      function was tested by Boyden Chamber assay. RESULTS: The purified HAb18G/CD147,
      identified by Western blot (molecular weight about 65 kd) could be used to bio
      pan the phage-displayed peptide library. After 3 rounds of bio-panning, 9
      positive phage clones were selected and sequenced. The synthesized peptides had
      uneven inhibitory activities and three of them were able to markedly inhibit the
      hepatoma cell invasion (P < 0.01). The most effective peptide decreased by 90.1%
      of hepatoma cells migrating through the Boyden Chamber membrane as compared with
      the control. CONCLUSION: Bio-panning the phage-displayed peptide library can be
      used successfully to screen out the antigen binding peptides. Hepatoma metastatic
      potential can be inhibited by peptide antagonist which could be a good foundation
      of developing peptide therapeutic agent against hepatoma metastasis.

PMID- 12795833
TI  - [Antitumor effects of soluble TRAIL in human hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate therapeutic potential of soluble TRAIL (sTRAIL) in
      hepatocellular carcinoma (HCC). METHODS: Expression of TRAILR was determined by
      in situ hybridization in 60 samples of resected hepatocellular carcinoma, 20
      samples of normal liver tissue near the margin of benign tumor and 2 HCC cell
      lines of HepG2 and SMMC-7721. The clinical data of the patients were analyzed as
      well as cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2
      and SMMC-7721 (p53 gene mutated) after exposure to different concentrations of
      recombinant protein. RESULTS: High death receptor (DR) expression and low DcR
      expression in HCC tissue differed from low DR expression and high DcR expression
      in the normal hepatic tissue with statistical significance. DR5, DR4, and DcR2
      but not DcR1 were expressed in both cell lines. The expression of DR was closely
      correlated with HCC differentiation, with the weak expression in poor
      differentiation. The positive rate of DR expression in 32 cases of grade III-IV
      was significantly lower than that in 28 cases of grade I-II (P < 0.05). Cell
      apoptosis rates were 10%, 70% and 50% of HCC cells, Jurkat cells and human
      cholangiocarcinoma cell line QBC939 24 h after recombinant of TRAIL alone.
      CONCLUSION: TRAILR expression is prevalent in HCC, with different receptor types
      existing. HCC is resistant to TRAIL-mediated apoptosis. The treatment of TRAIL
      alone only has a limited effect on inducing apoptosis on HCC cell lines of HepG2
      and SMMC-7721.

PMID- 12795834
TI  - [Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells
      HepG2].
AB  - OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced
      apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix
      related protein promyelocytic leukaemia (PML). METHODS: HepG2 cells were cultured
      in MEM medium and treated with different concentrations of As(2)O(3) for either
      24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling
      (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and
      western blot were performed to observe the expression of PML. RESULTS: TUNEL
      positive apoptotic cells and DNA ladder could be detected in As(2)O(3) treated
      groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L
      As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei
      almost disappeared after the treatment of 5 micro mol/L As(2)O(3). CONCLUSION:
      As(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration
      dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei.
      The decreased expression of PML is closely correlated with apoptosis. Nuclear
      matrix associated protein PML could be the target of As(2)O(3) therapy.

PMID- 12795835
TI  - [Expression and function of zinc ribbon gene ZNRD1 in drug-resistant gastric
      cancer cells].
AB  - OBJECTIVE: To study the expression and function of zinc ribbon gene ZNRD1 in drug
      resistant cells of gastric cancer. METHODS: Two tumor cell lines were used in
      this study: gastric cancer SGC7901 and its drug-resistant counterpart SGC7901/VCR
      stepwise-selected by vincristine. The expression of ZNRD1 in SGC7901 and
      SGC7901/VCR was detected by northern blot and semiquantitative RT-PCR. ZNRD1
      antisense nucleic acid was transfected into SGC7901/VCR cells by lipofectamine.
      The expression of protein in SGC7901/VCR cells and the transfectants was detected
      by immunochemical method. Fluorescence activated cell scan (FACS) was applied to
      observe the cell cycle alteration. Growth curve and drug sensitization of cells
      for vincristine (VCR) and adriamycin (ADM) were analyzed by MTT assay. RESULTS:
      The expression of ZNRD1 was higher in SGC7901/VCR than in SGC7901 cells.
      Immunochemical results showed that the expression level of ZNRD1 protein was
      lower in anti ZNRD1-SGC7901/VCR cells than in non-transfectants. The anti ZNRD1
      SGC7901/VCR cells were gradually accumulated in G(1) phase, with a concomitant
      decrease of cell population in S phase. MTT assay showed that transfectant cell
      proliferation was lagged and more sensitive to VCR and ADM than non
      transfectants. CONCLUSION: ZNRD1 gene displays high expression in VCR resistant
      gastric cancer cells. Expression of ZNRD1 protein is effectively blocked in anti
      ZNRD1-SGC7901/VCR cells by gene transfection. ZNRD1 antisense nucleic acid could
      reverse, to some degree, the MDR of human drug-resistant gastric cancer cell
      SGC7901/VCR.

PMID- 12795836
TI  - [Phosphorylated JNK mediated apoptosis induced by all trans retinoid acid in
      human retinoblastoma cell line].
AB  - OBJECTIVE: To investigate the mechanism of all trans retinoid acid (ATRA)
      inhibition of cell growth and induction of apoptosis in human retinoblastoma Y79
      cells. METHODS: Antiproliferating effects of ATRA on Y79 cells were studied by
      (3)H-thymidine incorporation. Cell cycle analysis was performed by flow
      cytometry, apoptosis of the ATRA-treated cells was determined by DNA
      fragmentation analysis and JNK phosphorylation analyzed by Western blot. RESULTS:
      After 36h treatment of 1 micro mol/L ATRA, (3)H-thymidine incorporation decreased
      to 40% with Y79 cells arrested in G(0)/G(1) and Sub-G(1) peak appeared. DNA
      ladder was observed in DNA fragmentation analysis after 36h treatment of ATRA.
      Curcumin, a JNK blocker, blocked the apoptosis and the growth inhibition induced
      by ATRA. JNK was phosphorylated in 10 to 20 min. CONCLUSION: ATRA can induce the
      apoptosis in Y79 cells by phosphorylation of JNK, which suggests that ATRA may
      have clinical application prospects for treatment of retinoblastoma.

PMID- 12795837
TI  - [Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].
AB  - OBJECTIVE: To establish human multidrug-resistant lung carcinoma cell line
      (D6/MVP) with its characteristics studied. METHODS: Intermittent administration
      of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell
      line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study
      the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was
      used to study the cell cycle distribution and the expression of P-gp, multidrug
      resistance-associated protein (MRP) and GSH/GST. RESULTS: 1. D6/MVP was resistant
      to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug
      resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was
      prolonged and the cell number of S-phase decreased while that of G1- and G(2)
      phase increased and 3. The expression of P-gp and MRP was enhanced significantly
      (96.2% vs 51.7%), but the expression of GSH/GST kept stable. CONCLUSION: D6/MVP
      is a multidrug-resistant cell line possessing the basic characteristics of drug
      resistance.

PMID- 12795838
TI  - [Peripheral blood mutated p53 DNA and its clinical value in human breast cancer].
AB  - OBJECTIVE: To evaluate the clinical value of mutated p53 in the peripheral blood
      of breast cancer patients. METHODS: Plasma DNA of 126 breast cancer patients and
      92 healthy women was examined. DNA extraction from the tumor and tissue samples
      was performed by a nonorganic method. Plasma DNA was purified on Qiagen columns.
      PCR-SSCP analysis was performed to examine the point mutations in the conserved
      exons 5, 6, 7 and 8 of TP53. RESULTS: The mean concentration of plasma DNA was 21
      ng/ml in healthy women and 211 ng/ml in patients with breast cancer (P < 0.01).
      p53 mutations in the primary tumor were detected in 46 of 126 (36.5%) breast
      cancer patients. Of these 46 patients, 30 (65.1%) were also found to have p53
      mutations in their plasma DNA. p53 mutation in plasma DNA was closely correlated
      with clinical stage, tumor size, lymph node (LN) metastasis and estrogen receptor
      status (P < 0.05). Survival of the patients with both primary tumor and plasma
      p53 mutations was the worst. Thirteen of the 22 (59.0%) patients with recurrence
      and/or metastasis had detectable p53 mutations in their plasma DNA. CONCLUSION:
      p53 mutations in plasma DNA may be a useful prognostic factor and an early marker
      of recurrence or distant metastasis in breast cancer.

PMID- 12795839
TI  - [Difference in expression of VEGF, bFGF and their receptors between the young and
      postmenopausal women with breast cancer].
AB  - OBJECTIVE: To study the difference in the expression of VEGF, bFGF and their
      receptors between young and postmenopausal women with breast cancer. METHODS: The
      expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women
      with breast cancer was studied by immunohistochemical method (SABC), with its
      relation with axillary lymph node metastasis and the clinical and pathologic
      characteristics. The expression index between these two groups was compared.
      RESULTS: The positive axillary lymph node rate and the mean expression of VEGF,
      bFGF in the young group were higher than postmenopausal group (P < 0.01 and P <
      0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary
      lymph node positive patients was higher than the negative ones both in young and
      postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant
      difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage
      III - IV (P < 0.05 and P < 0.01) in both groups. CONCLUSION: Breast cancer
      angiogenesis, characterized by the high expression of VEGF and bFGF, is directly
      correlated with the high tumor aggressiveness in the young women.

PMID- 12795840
TI  - [Significance of microvascular density and vascular endothelial growth factor in
      breast cancer].
AB  - OBJECTIVE: To study the significance of vascular endothelial growth factor (VEGF)
      and microvascular density (MVD) expression in breast cancer. METHODS: The
      expression of MVD and VEGF was studied in 81 patients with primary breast cancer
      by SP immunohistochemical technique. RESULTS: There were 49 patients with high
      VEGF expression (60.5%) and 35 patients with high MVD expression (43.2%). There
      was significant correlation between VEGF or MVD expression and TNM stage, but not
      age, tumor size, ER expression or lymph node status. VEGF was significantly
      related with MVD expression. Univariate analysis showed that patients with low
      expression of VEGF and MVD had longer disease free survival (DFS) and overall
      survival (OS). Grouping univariate analysis showed that VEGF had significant
      correlation with the DFS of all grouped patients and the OS of patients with
      LN(+) or stage III lesions. MVD had significant correlation with the DFS and OS
      of LN(+) patients and the DFS of stage III lesion patients. Multivariate analysis
      showed that MVD was a risk predictor because of its positive statistic value, the
      higher expression, the shorter survival time of the patients. CONCLUSION: Both
      VEGF and MVD are useful prognostic factors in breast cancer. MVD appears to be a
      strong and independent biologic marker for breast cancer prognosis.

PMID- 12795841
TI  - [Expression of different RASSF1 transcripts and its clinical significance in lung
      carcinoma].
AB  - OBJECTIVE: To evaluate the expression of three different RASSF1 transcripts and
      its clinical significance in lung carcinomas. METHODS: The mRNA expression of
      RASSF1A, RASSF1B and RASSF1C was detected by RT-PCR in 51 human lung cancer
      tissues and 51 matched normal tissues. RESULTS: 1. The mRNA expression of three
      RASSF1 transcripts was detectable in all non-cancer tissues. However, high rate
      of expression loss of RASSF1A and RASSF1B existed in lung cancer tissues, which
      was 53.2% (2851) and 37.3% (19/51), respectively. RASSF1C was expressed in all of
      the tumor tissues. 2. Loss or abnormal down-regulation of RASSF1A was positively
      related with lymph node metastasis and TNM stage (P < 0.05) and 3. RASSF1B and
      RASSF1C mRNA expression was not correlated with TNM stage, histological type,
      differentiation grade or smoking index. CONCLUSION: There is a significant
      expression difference among the three RASSF1 transcripts in lung carcinoma.
      RASSF1A, closely associated with lymph metastasis and TNM stage of lung
      carcinoma, should be a new tumor suppressor gene.

PMID- 12795842
TI  - [Value of serum-vascular endothelial growth factor in the differential diagnosis
      of solitary pulmonary nodule].
AB  - OBJECTIVE: To evaluate serum-vascular endothelial growth factor (S-VEGF) in the
      differentiation of solitary pulmonary nodule (SPN). METHODS: Serum level of VEGF
      of 68 patients with SPN was measured by ELISA kit, and compared with the control
      group of 20 normal subjects. The nodules were diagnosed by operation and
      pathology. RESULTS: The median level of S-VEGF was 42.5 (range from 10 to 170)
      pg/ml in the control, 44 (range from 18 to 360) pg/ml in benign nodule group and
      75 (range from 18 to 890) pg/ml in lung cancer group, with significant difference
      observed between the nodule group and control (P < 0.01), and between the lung
      cancer group and the benign nodule group (P < 0.05), but not between the benign
      nodule group and the control. In addition, when S-VEGF in different pathologic
      types of the limited number of lung cancer patients were compared, no significant
      difference was observed. CONCLUSION: S-VEGF is valuable in the differential
      diagnosis of solitary pulmonary nodule. An elevated S-VEGF level >or= 100 pg/ml
      in patients with SPN may strongly speak for a malignant nodule. Operation is
      suggested.

PMID- 12795843
TI  - [Clinico-pathologic and prognostic studies on lung adenocarcinoma patients under
      40 years of age].
AB  - OBJECTIVE: To study whether the clinico-pathologic characteristics and survival
      of young lung cancer patients < 40 years of age differ from those of lung cancer
      patients >or= 40 years of age. METHODS: Retrospective analysis was carried out to
      compare the clinico-pathologic features and survival of 129 young patients (young
      group) with those of 140 randomly selected older ones (elderly group). RESULTS:
      The young group, when compared with the older group, had more female (P = 0.037),
      longer mean duration of symptoms (4.7 m vs 2.5 m, P < 0.001), higher
      misdiagnostic rate (65.1% vs 24.3%, P < 0.001) with longer mean duration of
      misdiagnosis for the misdiagnosed patients (5.6 m vs 2.5 m, P < 0.001), more
      adenocarcinoma (54.3% vs 42.1%, P < 0.001), higher pathologic grade (69.5% vs
      36.0%, P < 0.001), more advanced-stage diseases at diagnosis (74.4% vs 45.7%, P <
      0.001), more patients receiving combined-modality treatment (94.6% vs 62.1%, P <
      0.001) and more distant failures as initial relapse (64.7% vs 50.6%, P = 0.02).
      The median survivals and 5-year survival rates were better in patients with stage
      I-II disease in the young group than the older group (54 m vs 33 m and 46.2% vs
      25.0%, P = 0.0495), even though the overall median survivals and 5-year survival
      rates were similar in either group (11 m vs 14 m and 8.3% vs 11.9%, P = 0.2889).
      There was no difference in family or smoking history (P = 0.227 and 0.171).
      CONCLUSION: Younger patients with lung cancer present difference in clinico
      pathologic features from the older ones, but the survivals of the two groups are
      similar. To define younger lung cancer as "the younger type of lung cancer" may
      have a practical clinical significance.

PMID- 12795844
TI  - [Significance of hRad17 mRNA expression in human gastric cancer].
AB  - OBJECTIVE: To study the relationship between hRad17 mRNA expression and
      clinicopathologic factors and lymph node metastasis of gastric cancer, and to
      assess the significance of predicting the extent of lymph node metastasis and
      prognosis. METHODS: hRad17 mRNA expression was examined in matched primary
      lesions, normal gastric mucosa and lymph node metastatic lesions among 52 gastric
      cancer patients by reverse transcription polymerase chain reaction (RT-PCR),
      polyacrylamide gel electrophoresis (PAGE) and silver stain with the relation
      between hRad17 mRNA expression and clinicopathologic factors analyzed. At the
      same time, hRad17 mRNA expressions in 5 gastric benign lesions and SGC7901
      gastric carcinoma cell lines were also examined. RESULTS: The primary tumor
      samples (88.4% positive) showed a significantly higher level of hRad17 expression
      compared with matched normal tissue (76.9% positive) (P = 0.014), so did the
      lymph node metastatic samples (94.2% positive) (P = 0.001). The hRad17 mRNA
      expression showed a low level in benign lesions, but very high in SGC7901 cell
      line. The hRad17 mRNA expression showed a higher level in patients with the
      number of lymph node metastasis above 15 than below 15 (P = 0.02), so did the
      diffused growth than the mass-like growth (P = 0.04). CONCLUSION: The method of
      PAGE and silver stain can improve the sensitivity of RT-PCR. The degree of lymph
      node metastasis and invasiveness of carcinoma cells are more serious in cases
      with hRad17 mRNA overexpression, and extensive lymph node dissection should be
      carried out for these patients. Examination of hRad17 expression by RT-PCR before
      surgery is indicated to arrive at an optimum treatment scheme and to estimate the
      prognosis.

PMID- 12795845
TI  - [A serial study of in cytogenetic change and morphology on the tetra-arsenic
      tetra-sulfide treatment in untreated or recurrent acute promyelocytic leukemia].
AB  - OBJECTIVE: To study the morphologic and cytogenetic change in acute promyelocytic
      leukemia (APL) patients during the tetra-arsenic tetra-sulfide (TATS) treatment
      and the mechanism of TATS. METHODS: The bone marrow cells of 13 newly diagnosed
      and 7 recurrent APL patients were studied through FISH and morphology during the
      TATS treatment by special and repeated marrow culture. RESULTS: Cytomorphological
      study of 8 cases (6 untreated and 2 recurrent) showed that TATS could
      differentiate APL cells forward to mature granulocytes. There was obvious
      correlation between the reduced t (15; 17) positive cells and the reduced APL
      cells (r range 0.7298 - 0.9989). Except one patient with t (11; 17), 19 (13
      untreated and 7 recurrent) with translocation t (15; 17) achieved clinical CR
      including 16 who achieved cytogenetic CR. CONCLUSION: TATS has a differentiation
      inducing effect on untreated and recurrent APL, with haematological CR and
      cytogenetic CR achieved. Measurement of t (15; 17) positive cells by FISH
      technique can reflect the change of APL cells objectively.

PMID- 12795846
TI  - [Tissue microarray and in situ hybridization study on hypoxia inducible factor
      1alpha mRNA expression in epithelial ovarian tumor].
AB  - OBJECTIVE: To study the expression and significance of hypoxia inducible factor
      1alpha (HIF-1alpha) in epithelial ovarian tumors. METHODS: The expression of HIF
      1alpha mRNA in 295 patients with epithelial ovarian tumor was analyzed
      retrospectively by high-throughput tissue microarray and in situ hybridization,
      which was compared with 13 normal ovarian tissue samples. RESULTS: The expression
      rates of HIF-1alpha mRNA were 0, 13.2%, 42.1% and 81.9% in normal ovarian tissue,
      benign, borderline and malignant ovarian tumors. Expression rate of HIF-1alpha
      mRNA in borderline and invasive tumor was significantly higher than those in
      normal ovarian tissue and benign tumor (P < 0.001). Statistical analysis revealed
      that the expression of HIF-1alpha mRNA was not related to FIGO stages or
      histological subtypes. Close negative relation was observed between the
      expression of HIF-1alpha mRNA and tumor histological differentiation (P < 0.001).
      CONCLUSION: The overexpression of HIF-1alpha may play an important role in
      oncogenesis of epithelial ovarian tumor. Tissue microarray is an efficient
      technique of molecular biology.

PMID- 12795847
TI  - [Oxaliplatin in combination with LV5FU2 for advanced/metastatic gastric cancer-a
      multicenter study].
AB  - OBJECTIVE: To evaluate the effects and safety of OXA-LV5FU2 regimen for patients
      with advanced/metastatic gastric cancer. METHODS: OXA 100 mg/m(2) i.v. 2hr d1,
      LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600
      mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was
      evaluated at 4 cycles (8 weeks). RESULTS: Forty three patients have been entered
      into the study. Patients with primary tumor resected or non-resected were 17 and
      26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12
      liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty
      patients were evaluable for clinical response. Four patients achieved CR (10.0%),
      13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%).
      Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated
      (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median
      time to progress (mTTP) was 5 months and median overall survival (mOS) was 8
      months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO
      toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients
      (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral
      neuropathy toxicity or any deaths during treatment. CONCLUSION: OXA-LV5FU2 is a
      high response regimen for advanced gastric cancer with mild toxicity, which can
      be practiced safely.

PMID- 12795848
TI  - [Peritoneal lavage cytology in 66 patients with gastric carcinoma].
AB  - OBJECTIVE: To evaluate the clinical and prognostic value of peritoneal lavage
      cytology (PLC) in detecting free cancer cells (FCC). METHODS: PLC of 66 gastric
      cancer patients being operated was prospectively analyzed to assess the
      prognostic significance of positive cytological finding and its relation with
      serosal invasion, lymph node metastasis and stage classification. RESULTS: The
      overall positive rate of cytology was 36.4% (24/66). These was a closely relation
      between positive cytology results and serosal invasion (P = 0.025), abdominal
      lymph node involvement (P < 0.005) and stage classification. Peritoneal
      recurrence in patients with positive cytological findings was significantly
      higher than that with negative results (P = 0.006 7). CONCLUSION: Micrometastasis
      to the abdominal cavity, formed by free cancer cells exfoliated from the tumor,
      are significantly responsible for peritoneal dissemination. Serosal invasion and
      metastatic nodes have greater risk for positive cytology and implies poor
      prognosis. Peritoneal lavage cytology, if practiced in all gastric cancer
      patients being operated, can predict the operative effect and prognosis, increase
      the accuracy of clinical stage and provide information for further adjuvant
      therapy.

PMID- 12795849
TI  - [Intraoperative radiotherapy for 30 esophageal carcinoma patients].
AB  - OBJECTIVE: To analyze the complications and treatment results of intraoperative
      radiotherapy (IORT) for esophageal carcinoma. METHODS: Sixty patients with
      thoracic esophageal carcinoma underwent esophagectomy through right thoractomy,
      30 patients of whom received IORT of 15 - 25 Gy. RESULTS: In patients who
      underwent IORT, 2 cases of pneumonitis, 1 case of anastomotic leak and 1 case of
      incisional wound infection were found. In patients underwent surgery only, 1 case
      of thoracic empyema and 1 case of anastomotic leak were found. All the
      complications ultimately healed. There was no operative mortality. During the
      follow-up of 3 years, in patients who underwent IORT, 2 of 3 died of radiation
      pneumonitis 24 and 26 months after IORT with one complicated with
      bronchoesophageal fistula. One of 3 died of multiple lung metastases. The 3-year
      survival rate was 88.0% (22/25) in IORT group and 76.0% (19/25) in surgery only
      group. CONCLUSION: Intraoperative radiotherapy can reduce locoregional recurrence
      if performed to thoracic esophageal carcinoma patients without surgical
      contraindication or distant metastasis. Radiation pneumonitis, a common
      complication difficult to manage, implies a poor prognosis and, consequently, the
      lung and bronchus should be protected from the radiation.

PMID- 12795850
TI  - [Selected CD34+ cell autologous transplantation for advanced malignant tumors].
AB  - OBJECTIVE: To determine the clinical results of selected CD34(+) cell autologous
      transplantation in advanced malignant tumors. METHODS: After pretreatment,
      fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant
      tumors were given the sorted CD34(+) cells collected by magnetic-activated cell
      sorting (Clini MACS, Milteny Biotech, Germany). RESULTS: Peripheral blood
      progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G
      CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell
      sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x
      10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2
      (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and
      platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and
      13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event
      free survival rate was 53.3% (8/15) and the overall survival rate was 66.7%
      (10/15). CONCLUSION: Transplantation of autologous selected PBPC CD34(+) cells
      gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being
      a safe approach, may improve the clinical outcome even in patients with advanced
      malignant tumors.

PMID- 12795851
TI  - [Adjustment of lipiodol dose according to tumor blood supply during the
      transcatheter arterial chemoembolization for large hepatic carcinoma by
      mulitdetector helical CT].
AB  - OBJECTIVE: To work out an individualized lipiodol dose in transcatheter arterial
      chemoembolization (TACE) for large hepatic carcinoma (HCC) according to its blood
      supply evaluated by CT. METHODS: One hundred patients with HCC (diameter more
      than 8 cm) were studied by triphasic 5-mm-thick-section scan of multidetector
      helical CT. Patterns of HCC blood supply were divided into sufficient blood
      supply, poor blood supply, mixed blood supply and arterial-venous shunt. The dose
      of ultra-fluid lipiodol was determined by diameter and blood supply type of HCC.
      The patients were divided two groups (50 cases each), with the lipiodol perfused
      according to the diameter and the blood supply of tumor in one group and the
      iodized oil perfused according to the actual tumor diameter in the other. The
      filling of lipiodol in HCC was observed and conformation rate was compared in the
      two groups. When the diameter of HCC was less than 10 cm, 10 - 20 ml and 5 - 10
      ml lipiodol was injected in to the sufficient blood supply and the poor supply
      groups. When the diameter of HCC was more than 10 cm, 20 - 30 ml iodized oil was
      injected in the sufficient blood supply group. The lipiodol dose in the mixed
      blood supply group was determined by the diameter of sufficient blood supply
      area. RESULTS: The conformation and effective rate were 82%, 84% in the first
      group and 36%, 46% in the second group (P < 0.01). CONCLUSION: A relative
      individualized lipiodol dose may be determined according to the blood supply
      pattern and the tumor diameter by CT imaging.

PMID- 12795852
TI  - [Multi-center prospective randomized trial on paclitaxel liposome and traditional
      taxol in the treatment of breast cancer and non-small-cell lung cancer].
AB  - OBJECTIVE: To analyze the effects and side effects of paclitaxel liposome formula
      on breast cancer and non-small cell lung cancer, compared with traditional taxol.
      METHODS: 129 patients from multicenters were prospectively randomized into a test
      group, given paclitaxel liposome at 135 mg/m(2) each session, and a control
      group, given traditional taxol at 135 mg/m(2) each session. Both groups received
      these regimens combined with ADM or DDP for two cycles (3 weeks per cycle).
      RESULTS: Of 129 cases, 128 were eligible for the analysis of side effects and 126
      for the overall response rate. The complete remission rate, partial remission
      rate and overall response rate were 1.6%, 33.3%, 34.9% in the test group and
      6.3%, 22.2%, 28.6% in the control group. There was no significant difference
      between the two groups. Though there was no significant difference in
      hematological toxicity between the two groups, the toxicity from the mixed
      solvent of polyethoxylated castor oil and ethanol was significantly lower in the
      test group than that in the control group. CONCLUSION: Paclitaxel liposome
      combined with ADM or DDP in the treatment of advanced breast cancer and non-small
      cell lung cancer, being similarly effective as taxol, can significantly lower the
      incidence of serious hypersensitive reactions.

PMID- 12795853
TI  - [Second-line Hycamtin in the treatment of lung cancer].
AB  - OBJECTIVE: To discuss the therapeutic effect and toxicity of second line Hycamtin
      for lung cancer patients. METHODS: Ten of these 21 patients had been treated with
      operation. All these 21 patients received second line Hycamtin treatment; given
      at the dose of 1.2 mg/m(2) per day, four consecutive days as one cycle and 21
      days as one course. A total of 1 - 4 courses were given according to the
      patient's tolerance. Four of these 21 patients also received combination of
      cisplatin. RESULTS: Among the 13 un-operated patients, two patients showed CR,
      six showed PR, three SD and two PD, giving an effective rate of 62%. Among the 8
      operated patients, seven showed SD but one developed distant metastasis. The 1
      year survival rate was 88%. TOXICITY: leukopenia I-II degree 14 (66.7%),
      leukopenia III-IV degree 5 (23.8%), thrombocytopenia III-IV degree 1 (4.8%) and
      one patient died of high fever and neutocytopenia. Nausea 8 (38.1%), vomiting 3
      (14.3%) and diarrhea 2 (9.5%) alopecia 4 (19.1%). Were the other side-effects.
      CONCLUSION: Hycamtin is indicated for second line therapy for lung cancer giving
      tolerable toxicity.

PMID- 12795854
TI  - [Treatment analysis of 26 patients with breast ductal carcinoma in situ].
AB  - OBJECTIVE: To study the appropriate surgical treatment for breast ductal
      carcinoma in situ (DCIS). METHODS: Twenty-six such patients treated between 1992
      and 2001 were retrospectively analyzed. Among them, 3 patients were treated by
      simple mastectomy, 23 patients by mastectomy and axillary lymph node dissection,
      8 patients by chemotherapy and one patient by radiotherapy after operation.
      Median follow-up was 42 m (rang 12 - 112 m). RESULTS: Except 3 of these 26
      patients lost in follow-up and 1 patient died from diabetes mellitus, all the
      other 22 patients survived over 5 years. All lymph nodes dissected from 23
      patients were negative. After surgery, 3 patients developed lymph edema of the
      arm. CONCLUSION: DCIS, lacking the potential of metastasis, is not invasive.
      Conservative breast surgery without lymph node dissection is feasible for most
      DCIS patients.

PMID- 12795855
TI  - Dog keeping in Taiwan: its contribution to the problem of free-roaming dogs.
AB  - This study conducted a quantitative ethnographic analysis of the influence of
      demographic factors and early experience (childhood exposure to dogs) on
      Taiwanese dog-keeping practices and behavior. A telephone survey of a randomly
      selected sample of 2001 Taiwan residents determined their dog ownership
      histories, current patterns of dog ownership and disposal, and other dog-related
      activities. The results suggest that low rates of neutering, easy availability of
      low- or no-cost puppies, a tendency to allow owned dogs free access to the
      outdoors, unrealistic expectations of dog ownership, canine behavioral problems,
      and religious and cultural taboos against euthanasia and shelter relinquishment
      have contributed to the recent increase in the numbers of free-roaming dogs in
      Taiwan. Logistic regression analyses determined that a relatively small number of
      demographic and experiential variables predicted dog ownership and disposal
      patterns. The most important of these was childhood experience of living with
      household dogs. In light of these findings, future efforts to reduce the stray
      dog problem should focus on enforcing registration fees, particularly for
      unsterilized animals; low-cost neutering schemes; and educational programs
      designed to promote neutering, improve knowledge of canine behavior and behavior
      problems, and develop more realistic expectations and attitudes toward dog
      ownership. Marked Taiwanese resistance to canine euthanasia and shelter
      relinquishment suggests a need for alternative methods of managing the existing
      free-roaming dog population.

PMID- 12795856
TI  - "Bark parks"--a study on interdog aggression in a limited-control environment.
AB  - As limited-control dog parks become more popular, concerns arise about whether
      these parks encourage interdog aggression. Systematic observations made at 1 park
      over 72 hr across 8 months found that 28 conflicts or potential conflicts
      occurred (< 0.5%). Of these, 14 were clear aggressive episodes. Each lasted less
      than 1 min (< 0.33% of total observation time). There were 14 other incidents of
      possible aggression that were ambiguous in nature. Each lasted less than 30 sec
      (< 0.17%). None of these incidents led to serious injury. Of the 177 dogs
      observed, only 9 were aggressive toward other dogs (5%): 6 aggressors, once each;
      2 aggressors, twice each; 1 aggressor, 3 times. Results indicate that aggression
      in limited-control dog parks may be relatively rare and probably presents only a
      limited risk to dogs and their caregivers (owners). In part, this may be because
      owners who frequent dog parks are self-selecting, self-monitoring, and self
      limiting in regard to dog aggression.

PMID- 12795857
TI  - The use of classical and operant conditioning in training Aldabra tortoises
      (Geochelone gigantea), for venipuncture and other, husbandry issues.
AB  - A variety of nonhuman animals in zoo and research settings have been the subjects
      of classical and operant conditioning techniques. Much of the published work has
      focused on mammals, husbandry training, and veterinary issues. However, several
      zoos are training reptiles and birds for similar procedures, but there has been
      little of this work published. Using positive reinforcement techniques enabled
      the training of 2 male and 2 female Aldabra tortoises (Geochelone gigantea) to
      approach a target, hold steady on target, and stretch and hold for venipuncture.
      This article discusses training techniques, venipuncture sight, and future
      training.

PMID- 12795858
TI  - Moving as a reason for pet relinquishment: a closer look.
AB  - One of the most frequently given reasons for relinquishing a companion animal to
      an animal shelter is that the person or family is moving. Telephone interviews
      conducted with 57 caregivers who relinquished animal companions to a shelter in
      the midwestern United States covered details of the move, characteristics both of
      the caregivers and the animals, and efforts to avoid relinquishment. A human
      nonhuman animal bonding scale also was administered. Although some participants
      had additional reasons for relinquishment, the majority had given up their pets
      solely because they were moving. Most had relatively low income, were moving for
      employment reasons, and were renting their homes. Landlord restrictions were an
      important factor in relinquishment. High scores on the bonding scale and
      spontaneous expressions of discomfort and sorrow suggest that external pressures
      overrode attachment to the animal and the pain of relinquishment.

PMID- 12795859
TI  - Legal loophole for subminimal floor area for caged macaques.

PMID- 12795871
TI  - Sixth annual scientific meeting of the International Society for Minimally
      Invasive Cardiac Surgery. June 19-21, 2003. San Francisco, California, USA.
      Abstracts.

PMID- 12795860
TI  - Review of the September 30, 2002 symposium on the "Evolving Legal Status of
      Chimpanzees"--Harvard Law School.

PMID- 12795872
TI  - International Society for Minimally Invasive Cardiac Surgery membership list.

PMID- 12796016
TI  - New approaches to cancer therapy.

PMID- 12796017
TI  - Vaccination of patients with solid tumours.
AB  - The molecular characterisation of human tumour antigens recognised by T cells has
      provided new impetus for immunisation of patients bearing tumours expressing well
      defined antigens. After evaluating the immunogenicity of the new, molecularly
      characterised antigens in vitro, several clinical studies were conducted to
      assess the in vivo immunogenicity and the clinical efficacy of vaccines including
      these antigens. The findings generated by trials based on the administration of
      peptides or DNA-encoding antigens are discussed to highlight the limits of this
      therapeutic approach; however, this approach has resulted in some complete and
      durable regressions, although still in a unsatisfactory small number of cases (5
      25%). The recent use of dendritic cells loaded ex vivo with tumour antigens
      suggests that a high frequency of tumour-specific immune responses can be
      achieved. Possible means of overcoming the clinical limits and improving the
      outcome of previous studies are also discussed.

PMID- 12796018
TI  - Towards an understanding of the biological basis of response to cisplatin-based
      chemotherapy in germ-cell tumors.
AB  - Chemotherapy is far more successful in young male patients with germ-cell tumors
      than in adults suffering from almost any other solid tumor. Various attempts have
      been made to understand the sensitivity of these tumors towards cisplatin-based
      chemotherapy; however, to date no explanation has been generally accepted. Recent
      data underline the need to seek further explanations, other than the previously
      postulated high intrinsic level of wild-type P53 protein, for the exquisite
      curability of germ-cell tumors. In this regard, the DNA repair pathways, in
      particular the DNA mismatch repair and nucleotide excision repair pathways, have
      received attention. This review summarizes the data currently available on the
      cellular basis for chemotherapy response in these tumors by systematically
      following cisplatin-presumably the most active drug in the treatment of this
      disease-on its course from entering the cell to the execution of apoptosis. The
      emerging picture points towards a multifactorial explanation for the unique
      chemosensitivity of germ-cell tumors, including a lack of export pumps, an
      inability to detoxify cisplatin and repair the respective DNA damage, and an
      intact apoptotic cascade not disturbed by anti-apoptotic stimuli. Even though no
      uniform pattern of relevant resistance factors has been identified in patients
      suffering from refractory disease, a significant number of these cases may be
      caused by defects in the DNA mismatch repair pathway.

PMID- 12796019
TI  - Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC
      regimen, day 1, 21) versus methotrexate in combination with fluorouracil and
      cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for
      operable breast cancer: a study by the GEICAM group.
AB  - BACKGROUND: The purpose of this study was to determine the relative efficacy of
      doxorubicin versus methotrexate in combination with intravenous cyclophosphamide
      and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast
      cancer. PATIENTS AND METHODS: Over a 4-year period, 985 women undergoing curative
      surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals
      were stratified with respect to axillary node involvement (node positive versus
      node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3
      weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles.
      RESULTS: The relative dose intensities of FAC and CMF were 87% and 85% of planned
      doses, respectively. Unadjusted data indicated a non-significant trend towards
      better results with FAC. In the prospectively formed subset of node-negative
      patients, disease-free survival and overall survival were statistically superior
      in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage
      was not seen in the subset of node-positive patients, probably because of a
      difference in the percentage of patients with four or more positive nodes.
      Adjusting data for size of treatment effect and potential interactions (number of
      positive nodes, tumor size, treatment center), the overall relative risk (RR) of
      disease recurrence and death were significantly lower with FAC treatment (RR 1.2,
      P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the
      difference observed in the node-negative patient population. Toxicity was mild:
      FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of
      clinical concern, but was infrequent and manageable. CMF induced more
      conjunctivitis and weight gain. There were no toxic deaths. CONCLUSIONS:
      Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is
      superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5
      fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment
      effect is particularly evident in the node-negative patients. Although the
      clinical toxicity of FAC is greater than that of CMF, the levels were manageable
      and clinically acceptable.

PMID- 12796020
TI  - Adjuvant systemic therapies in women with breast cancer: an audit of clinical
      practice in Italy.
AB  - BACKGROUND: Evidence-based guidelines, consensus conferences and experts' opinion
      are rarely promptly transferred to patient care. We audited prescriptions of
      adjuvant systemic therapies for Italian breast cancer patients and compared them
      with recommendations of an International Consensus Panel. PATIENTS AND METHODS:
      Disease characteristics and adjuvant therapies for 768 breast cancer patients
      referred to 87 Italian centers from 16 to 23 March 2000 were evaluated for
      adherence to the published recommendations. RESULTS: Endocrine therapy was not
      prescribed for 102 of 541 patients (19%) with endocrine-responsive disease and
      for 22 of 45 patients (49%) with unknown hormonal receptor status. Instead,
      endocrine therapy was prescribed for 22 of 182 patients (12%) with endocrine
      unresponsive disease. Adjuvant chemotherapy was prescribed for 98% of the
      patients. The type of chemotherapy was the cyclophosphamide, methotrexate, 5
      fluorouracil regimen for 453 of 754 (60%), while 253 of 754 (34%) received an
      anthracycline-based regimen. The proportion of patients with anthracyclines
      increased with the number of involved axillary nodes and grading, and decreased
      with age. Endocrine therapy was administered to 482 of 768 (63%) and was mainly
      represented by an antiestrogen. CONCLUSIONS: Lack of adherence to evidence-based
      guidelines for adjuvant treatment of Italian breast cancer patients was as high
      as 19%. It might be wise for national health authorities to promote education on
      life-saving procedures, like adjuvant systemic treatments, in cancer medicine.

PMID- 12796021
TI  - Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the
      completion of adjuvant chemotherapy in patients with operable breast cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the prognostic significance
      of the molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells in the
      peripheral blood of women with operable breast cancer after the completion of
      adjuvant chemotherapy. PATIENTS AND METHODS: Blood from 161 patients with stage I
      and II breast cancer, obtained after the completion of adjuvant chemotherapy, was
      tested by nested RT-PCR for CK-19 mRNA detection. Using univariate and
      multivariate analyses possible interactions with other prognostic factors and
      association of CK-19 mRNA detection with risk of relapse, disease-free interval
      (DFI) and overall survival were investigated. RESULTS: After completion of
      adjuvant chemotherapy, 27.3% of patients had peripheral blood CK-19 mRNA-positive
      cells; there was no association of this finding with any other prognostic factors
      or the type of chemotherapy regimen used. For patients with less than four
      involved axillary lymph nodes the risk of relapse was 3.81 [95% confidence
      interval (CI) 1.06-13.71] times higher, and the DFI was significantly reduced (P
      = 0.028) if CK-19 mRNA-positive cells were detectable in the blood after the
      completion of adjuvant chemotherapy. In contrast, for patients with four or more
      involved lymph nodes, the presence of CK-19 mRNA-positive cells after adjuvant
      chemotherapy did not significantly affect the risk of relapse or DFI.
      Furthermore, the risk of relapse was higher (hazards ratio 3.70; 95% CI 1.09
      13.89) and the DFI was reduced (P = 0.022) for patients with detectable CK-19
      mRNA-positive cells following adjuvant cyclophosphamide, methotrexate and 5
      fluorouracil (CMF) as compared with epirubicin, cyclophosphamide and 5
      fluorouracil (FEC) or sequential taxotere-epirubicin and cyclophosphamide (T/EC)
      chemotherapy. CONCLUSIONS: The detection of CK-19 mRNA-positive cells in the
      peripheral blood after adjuvant chemotherapy may be of clinical relevance for
      patients with early breast cancer and less than four involved axillary lymph
      nodes.

PMID- 12796022
TI  - Hepatic arterial infusion using pirarubicin combined with systemic chemotherapy:
      a phase II study in patients with nonresectable liver metastases from colorectal
      cancer.
AB  - BACKGROUND: A prospective phase II study was performed to determine the
      feasibility, efficacy and safety of arterial hepatic infusion (HAI) using
      pirarubicin combined with intravenous chemotherapy. PATIENTS AND METHODS: From
      December 1991 to April 1994, 75 patients with unresectable colorectal metastases
      confined to the liver were included in this multicenter study to receive intra
      arterial hepatic pirarubicin and a systemic monthly regimen of 5-fluorouracil (5
      FU) and folinic acid. Sixty-four patients were analyzed in the intention-to-treat
      analysis and 61 in the per-protocol analysis. RESULTS: Tolerance of this regimen
      was rather good; however, functional catheter problems were observed in 29
      patients (45%) resulting in failure of HAI in 21 cases (33%) after a median of
      three cycles; vomiting grade 3 was present in 12.5% of patients, neutropenia
      grade 4 in 23% and alopecia grade 3 in 19%. The overall response rate was 31.9%
      in intention-to-treat analysis, and 39.3% in per-protocol analysis. Extrahepatic
      progression was reported in only 21.7% of patients. Time to hepatic progression
      and extra-hepatic progression was 8.3 and 15 months, respectively, in intention
      to-treat analysis, and 11 and 18 months, respectively, in per-protocol analysis.
      Median survival was 19 and 20 months in intention-to-treat analysis and per
      protocol, respectively. CONCLUSIONS: In our study, the combination of intra
      arterial pirarubicin and intravenous chemotherapy demonstrated some efficacy and
      good tolerance in the treatment of isolated colorectal liver metastases. This
      treatment seems to prevent extra-hepatic spread and prolong survival time. The
      results of this study have to be confirmed by new trials using more active
      systemic chemotherapy.

PMID- 12796023
TI  - A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in
      patients with advanced gastrointestinal malignancies.
AB  - BACKGROUND: Oral eniluracil/5-fluorouracil (5-FU) was shown in early clinical
      studies to have promising activity against gastrointestinal malignancies.
      Oxaliplatin in combination with 5-FU also has activity against these tumour
      types. The primary objective of this study was to determine a tolerable dose for
      oral eniluracil/5-FU in combination with oxaliplatin. PATIENTS AND METHODS:
      Twenty-three patients with advanced gastrointestinal malignancies were recruited
      into this open-label study. Patients received a fixed dose of oxaliplatin (130
      mg/m(2) on the first day of a 21-day cycle), and the dose intensity of oral
      eniluracil/5-FU was gradually increased by escalating the number of days of
      treatment per course. RESULTS: The maximum tolerated dose intensity was
      eniluracil/5-FU 10.0/1.0 mg/m(2) twice daily for 16 days in combination with
      oxaliplatin 130 mg/m(2) on the first day of a 21-day cycle. Dose-limiting
      toxicities included vomiting and diarrhoea. The objective tumour response rate
      was 26% with a median duration of response of 15.3 weeks (95% confidence interval
      8.5-22.1). Twenty-two patients (96%) experienced neurotoxicity (sensory
      neuropathy or cold-related dysaesthesia), although only two events were severe
      (grade 3). CONCLUSIONS: The recommended dose for future study in patients with
      advanced gastrointestinal cancer is 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice
      daily for 14 days in combination with oxaliplatin 130 mg/m(2) on the first day of
      each treatment cycle.

PMID- 12796024
TI  - Multicenter study evaluating a dual policy of postorchiectomy surveillance and
      selective adjuvant single-agent carboplatin for patients with clinical stage I
      seminoma.
AB  - BACKGROUND: After decades of irradiation as standard therapy for clinical stage I
      testicular seminoma, alternative treatment approaches have emerged including
      postorchiectomy surveillance and adjuvant chemotherapy. This study was performed
      to assess a dual policy of surveillance and selective single-agent carboplatin
      (for high-risk cases) in a multicenter setting. PATIENTS AND METHODS: From 1994
      to 1999, 203 patients with stage I seminoma were included. Sixty (29.6%) were
      considered poor-risk cases (i.e. with vascular invasion and/or pathological tumor
      stage pT2 or greater) and received two courses of adjuvant carboplatin, whereas
      143 (70.4%) without risk criteria underwent close surveillance. RESULTS: Median
      follow-up was 52 months (range 14-92). Relapses were observed in two (3.3%)
      patients treated with carboplatin and in 23 patients (16.1%) on surveillance,
      with a median time to recurrence of 11 months (range 3.9-39.6). All relapsing
      patients were rendered disease-free, mainly with cisplatin-based chemotherapy.
      Four patients died from tumor-unrelated causes. Actuarial 5-year overall survival
      was 96.7% and cause-specific survival was 100%. Five-year disease-free survival
      was 83.5% for patients on surveillance, and 96.6% for those receiving
      carboplatin. CONCLUSIONS: This dual treatment policy is feasible in a multicenter
      setting and preserves 70% of patients from adjuvant chemotherapy. Single-agent
      carboplatin is effective in reducing the relapse rate in patients with high-risk
      stage I seminoma. A better definition of local risk features would probably
      improve patient selection, thus minimizing the incidence of recurrences on
      surveillance.

PMID- 12796025
TI  - Expression of KIT and epidermal growth factor receptor in chemotherapy refractory
      non-seminomatous germ-cell tumors.
AB  - BACKGROUND: The majority of patients with germ-cell tumors (GCTs) are curable
      with standard therapy. The molecular differences between curable and incurable
      disease are unknown. We have studied the expression of KIT and the epidermal
      growth factor receptor (EGFR) to determine their incidence in chemorefractory
      disease. PATIENTS AND METHODS: We retrospectively analyzed 23 patients with
      chemorefractory non-seminomatous GCTs (15 late relapse and eight transformed
      teratomas). None of these 23 patients were cured by their initial chemotherapy
      and/or surgery. Immunohistochemical analysis of KIT and EGFR was performed on the
      most recently available specimen from a metastatic site. PCR amplimers of KIT
      exon 17 were screened for mutations by a combination of denaturing high
      performance liquid chromatography and direct sequencing. RESULTS: KIT was
      expressed (>/=10% of the tumor displaying membranous or cytoplasmic staining) in
      11 of 23 GCT patients [48%; 95% confidence interval (CI) 26% to 68%]. There were
      no activating KIT mutations in the phosphoryltransferase domain (exon 17) in 21
      patients analyzed. EGFR was expressed (1+ to 3+) in 15 of 23 GCT patients (65%;
      95% CI 41% to 82%). CONCLUSIONS: KIT and EGFR are expressed in a significant
      proportion of refractory GCTs. The significance of these findings will be
      determined by ongoing clinical trials.

PMID- 12796027
TI  - CD117 (c-KIT) overexpression in patients with extensive-stage small-cell lung
      carcinoma.
AB  - BACKGROUND: The aim of this study was to determine the incidence and role of
      CD117 (c-KIT) overexpression as a predictive/prognostic marker in extensive-stage
      small-cell lung carcinoma (ESSCLC). We performed a retrospective study on
      subjects with a biopsy-proven diagnosis of ESSCLC. PATIENTS AND METHODS: A chart
      review for demographic and clinical data was performed on patients with ESSCLC
      diagnosed between 1991 and 2001. CD117 overexpression was evaluated using
      immunohistochemistry (A4052 polyclonal antibody) performed on archival paraffin
      embedded specimens. RESULTS: Two hundred and twenty-three patients with ESSCLC
      were identified, of whom 193 (84 females, 109 males) with a mean age of 68.5
      years (range 42-90) had adequate tissue specimens available for CD117 testing.
      The most commonly presenting symptom was weight loss, seen in 61 patients
      (31.6%). Of the 193 specimens, 54 (27.9%) showed CD117 overexpression. The median
      length of survival for CD117-positive patients was 9 months as compared with the
      CD117-negative population, in whom the survival was 6 months (P = 0.025, Cox
      proportional hazard method). CONCLUSIONS: CD117 overexpression detected using
      immunohistochemistry is observed in about a third of patients with ESSCLC and
      does not have statistically significant prognostic value. However, CD117 may be a
      potential target for site-specific immunotherapy in ESSCLC. Our findings suggest
      a role for clinical trials assessing the role of selective tyrosine kinase
      inhibitor STI-571 (alone or in combination with conventional therapy) in patients
      with ESSCLC.

PMID- 12796026
TI  - Practicability and acute haematological toxicity of 2- and 3-weekly CHOP and
      CHOEP chemotherapy for aggressive non-Hodgkin's lymphoma: results from the NHL-B
      trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
AB  - BACKGROUND: There is evidence that intensified variants of the classical 3-weekly
      CHOP-21 chemotherapy [cyclophosphamide (C), doxorubicin (H), vincristine (O),
      prednisone (P)] may improve treatment outcome in aggressive lymphoma. Three
      variants using either an addition of etoposide (CHOEP-21: 100 mg/m(2) on days 1
      3), the shortening to 2-week intervals using recombinant human granulocyte colony
      stimulating factor (rhG-CSF; CHOP-14) or both (CHOEP-14) are currently compared
      with CHOP-21 in the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma
      Study Group (DSHNHL). To enable more extensive testing of these schemes we here
      characterise their practicability regarding schedule adherence, acute
      haematotoxicity and need for supportive treatment. PATIENTS AND METHODS: The
      trial included patients with normal lactate dehydrogenase (LDH) aged </=60 years
      (NHL-B1) and patients aged 61-75 years (NHL-B2). The data are taken from an
      interim analysis. Data from 959 patients (CHOP-21: 232; CHOP-14: 238; CHOEP-21:
      244; CHOEP-14: 245) from 162 institutions with a total of 5331 therapy cycles
      were evaluated. RESULTS: The dose adherence in the NHL-B1 trial was excellent.
      The median relative dose (RD; i.e. actually given compared to planned dose)
      exceeds 98% for the myelosuppressive drugs in all four regimens. Only </=5% of
      patients received a relative dose <80% (RD <80). The median treatment duration
      could be shortened as scheduled for both CHOP-14 by 36 days and CHOEP-14 by 35
      days. The dose adherence in the NHL-B2 trial was excellent for CHOP-21 and CHOP
      14 for the myelosuppressive drugs (median RD >/=98%, RD <80 </=15%). Addition of
      etoposide, however, was accompanied by more dose erosion (median RD >/=97%, RD
      <80 </=17% for CHOEP-21 and </=27% for CHOEP-14). The median treatment duration
      could be shortened by 34 days with CHOP-14 compared with CHOP-21. Less treatment
      shortening was feasible for CHOEP-14 compared with CHOP-21 (median of 29 days).
      CHOP-14 and CHOP-21 were similar regarding toxicity profile, rate of infection,
      use of antibiotics, rate of transfusions and hospitalisation. CHOEP schemes were
      associated with a higher rate of infections, more transfusion requirements, more
      antibiotic use and longer hospitalisation than the CHOP schemes, particularly in
      patients aged >60 years. Haematopoietic recovery was age- and treatment-related.
      CONCLUSIONS: CHOP-14 with the addition of rhG-CSF is safe and practicable in a
      large multicentre setting in patients aged 18-75 years. Despite shorter treatment
      intervals it can be delivered at the same dose as the classical 3-weekly CHOP
      with a comparable toxicity profile. The addition of etoposide is feasible and
      safe for patients </=60 years old in both the CHOEP-21 and CHOEP-14 schemes. For
      patients >60 years of age the addition of etoposide is associated with marked
      dose erosion due to increased toxicity. In this age group CHOEP should be used
      with caution.

PMID- 12796028
TI  - Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl
      and Sky in human uterine endometrial cancers.
AB  - BACKGROUND: Gas6, the protein product of the growth arrest-specific gene 6
      (gas6), a member of the vitamin K-dependent protein family, was identified as a
      ligand for the Axl/Sky family of receptor tyrosine kinases. Gas6 acts as a growth
      potentiating factor for thrombin-induced proliferation of vascular smooth muscle
      cells. The aim of the present study was to test for the presence of Gas6 and its
      receptors Axl and Sky, related to specific growth in uterine endometrial cancers,
      and to evaluate their plausible growth potential and mechanism. MATERIALS AND
      METHODS: Sixty patients underwent curative resection for uterine endometrial
      cancers. In uterine endometrial cancers, the mRNA levels and histoscores of Gas6,
      Axl and Sky were determined by competitive RT-PCR using recombinant RNA and
      immunohistochemical studies, respectively. The rate of proliferation by
      immunochemistry for Ki67 and the rate of apoptosis by TUNEL were determined.
      RESULTS: The mRNA levels and the histoscores of Gas6 and Axl in well
      differentiated endometrial cancers (G1 EC) were significantly higher than in
      normal uterine endometrium (NE) and in moderately and poorly differentiated
      endometrial cancers (G2 + G3 EC). The rate of apoptosis in G1 EC was
      significantly lower than that in NE and in G2 + G3 EC. CONCLUSIONS: Gas6 and Axl
      signal transduction is aberrantly stimulated in well-differentiated endometrial
      cancers, plausibly related to tumor progression due to protection from apoptosis
      in cancers cells.

PMID- 12796029
TI  - Energy, macronutrients and laryngeal cancer risk.
AB  - BACKGROUND: A role for diet in laryngeal carcinogenesis has been suggested, but
      only a few studies have examined the potential relationship with a wide variety
      of macronutrients. PATIENTS AND METHODS: A case-control study was conducted
      between 1992 and 2000 in Italy and Switzerland, including 527 incident cases of
      laryngeal cancer, and 1297 controls hospitalized for acute, non-neoplastic
      conditions. The subjects' usual diet was investigated through a validated food
      frequency questionnaire, including 78 foods and beverages. Odds ratios (ORs) and
      95% confidence intervals (CIs) were estimated using unconditional multiple
      logistic regression models. RESULTS: Cases reported higher energy intake than
      controls. The continuous OR for 100 kcal/day was 1.16 (95% CI 1.12-1.21) for
      alcohol energy, and 1.02 (95% CI 1.01-1.04) for non-alcohol energy. A
      significantly increased risk of laryngeal cancer was observed for animal protein
      (continuous OR = 1.21, 95% CI 1.03-1.41), polyunsaturated fats other than
      linoleic and linolenic fatty acids (OR = 1.43, 95% CI 1.19-1.70), and cholesterol
      intake (OR = 1.43, 95% CI 1.19-1.71). Laryngeal cancer risk was slightly reduced
      with increasing vegetable protein (OR = 0.75, 95% CI 0.62-0.91), sugar (OR =
      0.84, 95% CI 0.71-1.00) and monounsaturated fatty acid intake (OR = 0.83, 95% CI
      0.70-0.99). CONCLUSIONS: Laryngeal cancer cases have a higher energy intake than
      control subjects, and report a higher intake of animal protein and cholesterol.

PMID- 12796030
TI  - Phase I and pharmacokinetic study of the topoisomerase I inhibitor, exatecan
      mesylate (DX-8951f), using a weekly 30-minute intravenous infusion, in patients
      with advanced solid malignancies.
AB  - BACKGROUND: The topoisomerase I inhibitor exatecan mesylate (DX-8951f ) is a
      water-soluble hexacyclic analogue of camptothecin that does not require enzymatic
      activation. This study determined the toxicity, maximum tolerated dose (MTD),
      pharmacokinetics and pharmacodynamics of a weekly intravenous (i.v.) schedule of
      DX-8951f. PATIENTS AND METHODS: Thirty-five patients with advanced solid
      malignancies, stratified as minimally (MP) or heavily (HP) pre-treated, received
      escalating doses of DX-8951f as 30-min i.v. infusions for three out of every 4
      weeks. Pharmacokinetics were described after the first infusion of DX-8951f.
      RESULTS: Infusions (244) of DX-8951f were administered with a median of two
      cycles (range 1-10). The main toxicity observed was haematological. There was no
      significant gastrointestinal toxicity. Two patients (6%) had confirmed partial
      responses. Twelve patients (39%) had stable disease. DX-8951f had a terminal
      elimination half-life of approximately 8 h and a clearance of 2 l/h/m(2). The
      area under the plasma concentration versus time curve (AUC( infinity )) and the
      maximum plasma concentration (C(max)) increased linearly with the dose. A linear
      relationship was present for the percentage decrease in neutrophil counts or
      platelet counts and AUC( infinity ) as well as C(max). CONCLUSIONS: The dose
      limiting toxicity of DX-8951f is neutropenia for MP patients and neutropenia and
      thrombocytopenia for HP patients. Evidence for clinical activity was seen,
      suggesting phase II study of the drug is indicated. Using this schedule the
      recommended dose is 2.75 mg/m(2)/week for MP patients and 2.10 mg/m(2)/week for
      HP patients.

PMID- 12796032
TI  - Phase I and pharmacokinetic study of CCI-779, a novel cytostatic cell-cycle
      inhibitor, in combination with 5-fluorouracil and leucovorin in patients with
      advanced solid tumors.
AB  - BACKGROUND: CCI-779 is a novel ester of the immunosuppressive agent sirolimus
      that exerts cytostatic effects by the inhibition of the translation of cell-cycle
      regulatory proteins. We investigated the maximum tolerated dose (MTD) and
      pharmacokinetics (PK) of CCI-779 in combination with leucovorin (LV) and 5
      fluorouracil (5-FU) in patients with advanced solid tumors. PATIENTS AND METHODS:
      Patients were treated with LV at 200 mg/m(2) as a 1-h i.v. infusion directly
      followed by continuous 24-h i.v. infusion of 5-FU, in the first patient at 2000
      mg/m(2) and in subsequent patients at 2600 mg/m(2). CCI-779 was administered
      directly prior to LV as a 30-min i.v. infusion at a starting dose of 15 mg/m(2)
      beginning at day 8 and escalated in subsequent cohorts of patients. One cycle
      consisted of six weekly administrations followed by 1 week of rest. Blood samples
      were drawn to assess PK of CCI-779 as well as its effect on steady-state 5-FU
      exposures. RESULTS: Twenty-eight patients entered the study, the majority having
      tumor types for which 5-FU is used as a treatment. CCI-779 doses of 15, 25, 45
      and 75 mg/m(2) were investigated. Skin toxicity (rash) was prominent at all dose
      levels examined. Stomatitis was the dose-limiting toxicity (DLT) for 75 mg/m(2)
      doses of CCI-779. Subsequently the cohort at 45 mg/m(2) was expanded to a total
      of 15 patients, and at this dose level two treatment-related deaths occurred due
      to mucositis with bowel perforation. Based on the toxicities observed, it was
      decided to discontinue the study. Partial responses were observed in three
      patients with gastrointestinal tumors. No pharmacokinetic interaction between CCI
      779 and 5-FU was observed. CONCLUSIONS: The safety profiles of CCI-779 and 5
      FU/LV suggest an overlap of drug-related toxicities, and the administration of
      these drugs at these doses and schedule resulted in unacceptable toxicity and
      therefore cannot be recommended. If CCI-779 is to be used in combination with 5
      FU/LV, other doses or schedules of administration will need to be explored.

PMID- 12796031
TI  - Phase I pharmacokinetic trial of the selective oral epidermal growth factor
      receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese
      patients with solid malignant tumors.
AB  - BACKGROUND: This phase I dose-escalating study investigated the tolerability and
      toxicity of the selective epidermal growth factor receptor tyrosine kinase
      inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors.
      Thirty-one patients were included. PATIENTS AND METHODS: Patients initially
      received a single oral dose of gefitinib followed by 10-14 days of observation.
      Oral gefitinib was subsequently administered on 14 consecutive days, every 28
      days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose
      limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the
      most frequent were an acne-like rash and gastrointestinal effects. Two of six
      patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was
      reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal
      half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial
      response (duration 35-361 days) was observed in five of the 23 patients with non
      small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients
      with a range of tumors had disease stabilization (duration 40-127 days).
      CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in
      Japanese patients. The safety profile, pharmacokinetic parameters and antitumor
      activity observed in our study are comparable to those observed in patients from
      the USA and Europe.

PMID- 12796033
TI  - Loss of atm sensitises p53-deficient cells to topoisomerase poisons and
      antimetabolites.
AB  - BACKGROUND: Ataxia-telangiectasia is a pleiotropic autosomal recessive disorder
      caused by mutations in the ATM gene. In addition to a profound cancer
      predisposition, another hallmark of ataxia-telangiectasia is radiosensitivity.
      Recently, p53-null mouse fibroblasts have been reported to be radiosensitised by
      the concurrent loss of ATM. MATERIALS AND METHODS: We compared the sensitivity of
      atm(+/+)/p53(-/-) and atm(-/-)/p53(-/-) mouse embryonic fibroblasts to different
      classes of chemotherapeutic agents using the MTT assay, Trypan Blue exclusion and
      fluorescence-activated cell sorting for cell cycle and apoptosis analyses.
      RESULTS: Loss of ATM function in p53-deficient cells resulted in a 2- to 4-fold
      increase in sensitivity to the topoisomerase I poisons camptothecin and
      topotecan, to the topoisomerase II poisons doxorubicin, epirubicin and etoposide,
      and to the antimetabolites 5-fluorouracil and gemcitabine, but not to the
      platinum compounds cisplatin, carboplatin and oxaliplatin, the taxanes docetaxel
      and paclitaxel, or to busulfan. Loss of ATM function did not result in increased
      apoptosis, but resulted in increased Trypan Blue staining in response to
      epirubicin, suggesting that processes other than apoptosis may mediate
      cytotoxicity. ATM deficiency did not alter the extent of G(1)/S or G(2)/M cell
      cycle phase accumulation produced by epirubicin, suggesting that enhanced
      sensitivity was not due to failure of checkpoint activation. CONCLUSIONS: We
      provide further evidence that ATM is involved in regulating cellular defences
      against some cytotoxic agents in the absence of p53. Tumour-targeted functional
      inhibition of ATM may be a valuable strategy for increasing the efficacy of
      anticancer agents in the treatment of p53-mutant cancers.

PMID- 12796034
TI  - Cancer prevalence in Northern Europe: the EUROPREVAL study.
AB  - BACKGROUND: Information on cancer prevalence is of importance for health planning
      and resource allocation, but is not always available. In order to obtain such
      data in a comparable way a systematic evaluation of cancer prevalence in Europe
      was undertaken within the EUROPREVAL project. PATIENTS AND METHODS: Standardised
      data were collected from 38 population-based registries on almost 3 million
      cancer patients diagnosed between 1970 and 1992. The prevalence of 11 specific
      cancer types was estimated at the index date of 31 December 1992. This study
      deals with the northern countries Denmark, Estonia, Finland, Iceland and Sweden.
      RESULTS: There were large differences between these countries, Sweden having the
      highest prevalence rate of 3050 per 100 000 and Estonia the lowest, 1339 per 100
      000. This difference is mainly due to a high proportion of cancers with
      favourable prognosis such as breast cancer, prostate cancer and melanoma, better
      survival and longer life expectancy in Sweden, whereas Estonia has a higher
      proportion of stomach and lung cancer with poor prognosis, worse survival and
      much shorter life expectancy, especially for males. For most tumour types, the
      Nordic countries did better than Estonia. There are indications that cancer
      patients in Estonia, as well as in Denmark, have a more advanced stage at
      diagnosis and that the Estonian health-care system is less efficient.
      CONCLUSIONS: Despite many similarities and a common historical background, the
      northern countries in Europe that participated in the EUROPREVAL study display
      quite different cancer patterns and prevalence. Reasons for these variations are
      discussed.

PMID- 12796035
TI  - Minidose warfarin is associated with a high incidence of International Normalized
      Ratio elevation during chemotherapy with FOLFOX regimen.

PMID- 12796036
TI  - Fatal hepatic failure due to gemcitabine and vinorelbine.

PMID- 12796037
TI  - A case report of oxaliplatin extravasation.

PMID- 12796038
TI  - Fluctuation of intratumor biological variables as a function of menstrual timing
      of surgery for breast cancer in premenopausal patients.

PMID- 12796039
TI  - Severe hemolytic anemia and skin reaction in a patient treated with imatinib.

PMID- 12796040
TI  - Airborne particulate matter and mortality: timescale effects in four US cities.
AB  - While time-series studies have consistently provided evidence for an effect of
      particulate air pollution on mortality, uncertainty remains as to the extent of
      the life-shortening implied by those associations. In this paper, the authors
      estimate the association between air pollution and mortality using different
      timescales of variation in the air pollution time series to gain further insight
      into this question. The authors' method is based on a Fourier decomposition of
      air pollution time series into a set of independent exposure variables, each
      representing a different timescale. The authors then use this set of variables as
      predictors in a Poisson regression model to estimate a separate relative rate of
      mortality for each exposure timescale. The method is applied to a database
      containing information on daily mortality, particulate air pollution, and weather
      in four US cities (Pittsburgh, Pennsylvania; Minneapolis, Minnesota; Seattle,
      Washington; and Chicago, Illinois) from the period 1987-1994. The authors found
      larger relative rates of mortality associated with particulate air pollution at
      longer timescale variations (14 days-2 months) than at shorter timescales (1-4
      days). These analyses provide additional evidence that associations between
      particle indexes and mortality do not imply only an advance in the timing of
      death by a few days for frail individuals.

PMID- 12796041
TI  - Invited commentary: Timescale-dependent mortality effects of air pollution.

PMID- 12796043
TI  - Modifiers of the temperature and mortality association in seven US cities.
AB  - This paper examines effect modification of heat- and cold-related mortality in
      seven US cities in 1986-1993. City-specific Poisson regression analyses of daily
      noninjury mortality were fit with predictors of mean daily apparent temperature
      (a construct reflecting physiologic effects of temperature and humidity), time,
      barometric pressure, day of the week, and particulate matter less than 10 micro m
      in aerodynamic diameter. Percentage change in mortality was calculated at 29
      degrees C apparent temperature (lag 0) and at -5 degrees C (mean of lags 1, 2,
      and 3) relative to 15 degrees C. Separate models were fit to death counts
      stratified by age, race, gender, education, and place of death. Effect estimates
      were combined across cities, treating city as a random effect. Deaths among
      Blacks compared with Whites, deaths among the less educated, and deaths outside a
      hospital were more strongly associated with hot and cold temperatures, but gender
      made no difference. Stronger cold associations were found for those less than age
      65 years, but heat effects did not vary by age. The strongest effect modifier was
      place of death for heat, with out-of-hospital effects more than five times
      greater than in-hospital deaths, supporting the biologic plausibility of the
      associations. Place of death, race, and educational attainment indicate
      vulnerability to temperature-related mortality, reflecting inequities in health
      impacts related to climate change.

PMID- 12796044
TI  - Exploring the effects of methylenetetrahydrofolate reductase gene variants C677T
      and A1298C on the risk of orofacial clefts in 261 Norwegian case-parent triads.
AB  - Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both
      been implicated in the etiology of orofacial clefts. The authors selected 261
      case-parent triads (173 cases with cleft lip with or without cleft palate (CL/P)
      and 88 cases with cleft palate only (CPO)) from a Norwegian population-based
      study of orofacial clefts (May 1996-1998). A case-parent triad design was used to
      examine whether MTHFR variants C677T and A1298C, and their haplotypes, are risk
      factors for orofacial clefts. Among CL/P cases, the child's genotype at C677T or
      A1298C did not influence the risk. However, children of mothers carrying the
      C677T variant allele had a lower risk of CL/P. For CPO, children carrying the
      C677T variant allele had about a twofold increased risk, whereas the mother's
      genotypes did not contribute to the risk. The haplotype-based
      transmission/disequilibrium test showed that except for 677T/1298A (p = 0.06),
      none of the other haplotypes showed evidence of excess transmission to the
      offspring. The authors also explored interaction of C677T with maternal use of
      folic acid among children with CPO. Surprisingly, the risk associated with the
      child's carrying either CT or TT was higher (fourfold) when the mother used folic
      acid. These findings suggest a possible role of MTHFR and folic acid in the
      causation of orofacial clefts, but the strength and direction of these effects
      remain to be clarified.

PMID- 12796045
TI  - Abnormal glucose tolerance and the risk of cancer death in the United States.
AB  - Although abnormal glucose tolerance is a well-established risk factor for
      cardiovascular disease, its relation to cancer risk is less certain. Therefore,
      the authors performed a prospective cohort study using data from the Second
      National Health and Nutrition Examination Survey and the Second National Health
      and Nutrition Examination Survey Mortality Study to determine this relation. This
      analysis focused upon a nationally representative sample of 3,054 adults aged 30
      74 years who underwent an oral glucose tolerance test at baseline (1976-1980).
      Deaths were identified by searching national mortality files through 1992. Adults
      were classified as having either previously diagnosed diabetes (n = 247),
      undiagnosed diabetes (n = 180), impaired glucose tolerance (n = 477), or normal
      glucose tolerance (n = 2250). There were 195 cancer deaths during 40,024 person
      years of follow-up. Compared with those having normal glucose tolerance, adults
      with impaired glucose tolerance had the greatest adjusted relative hazard of
      cancer mortality (relative hazard = 1.87, 95% confidence interval (CI): 1.06,
      3.31), followed by those with undiagnosed diabetes (relative hazard = 1.31, 95%
      CI: 0.48, 3.56) and diabetes (relative hazard = 1.13, 95% CI: 0.49, 2.62). These
      data suggest that, in the United States, impaired glucose tolerance is an
      independent predictor for cancer mortality.

PMID- 12796046
TI  - Incidence of heart failure after myocardial infarction: is it changing over time?
AB  - Improved survival after myocardial infarction (MI) could result in MI survivors'
      contributing to the US heart failure epidemic. Conversely, since the severity of
      MI is declining over time, a decline in post-MI heart failure might also be
      anticipated. This study tested the hypothesis that the incidence of post-MI heart
      failure was declining over time in a geographically defined MI incidence cohort.
      Between 1979 and 1994, 1,537 patients with incident MI and no prior history of
      heart failure were hospitalized in Olmsted County, Minnesota. Framingham Heart
      Study criteria were used to ascertain the incidence of inpatient and outpatient
      heart failure over a mean follow-up period of 7.6 years (standard deviation 5.5).
      Overall, 36% of patients experienced heart failure. After adjustment for factors
      related to post-MI heart failure (age, hypertension, smoking, and biomarkers),
      the incidence of heart failure declined by 2% per year (relative risk = 0.98, 95%
      confidence interval: 0.96, 0.99; p = 0.01). The relative risk of developing heart
      failure among persons with MIs occurring in 1994 versus 1979 was 0.72 (95%
      confidence interval: 0.55, 0.93), indicating a 28% reduction in the incidence of
      heart failure. Administration of reperfusion therapy within 24 hours after MI was
      associated with lower risk of post-MI heart failure and accounted for most of the
      temporal decline in heart failure. This suggests that improved survival after MI
      is unlikely to be a major contributor to the heart failure epidemic.

PMID- 12796047
TI  - Abortion, changed paternity, and risk of preeclampsia in nulliparous women.
AB  - A prior birth confers a strong protective effect against preeclampsia, whereas a
      prior abortion confers a weaker protective effect. Parous women who change
      partners in a subsequent pregnancy appear to lose the protective effect of a
      prior birth. This study (Calcium for Preeclampsia Prevention Trial, 1992-1995)
      examines whether nulliparous women with a prior abortion who change partners also
      lose the protective effect of the prior pregnancy. A cohort analysis was
      conducted among participants in this large clinical trial of calcium
      supplementation to prevent preeclampsia. Subjects were nulliparous, had one prior
      pregnancy or less, delivered after 20 weeks' gestation, and were interviewed at 5
      21 weeks about prior pregnancies and paternity. Women without a history of
      abortion served as the reference group in logistic regression analyses. Women
      with a history of abortion who conceived again with the same partner had nearly
      half the risk of preeclampsia (adjusted odds ratio = 0.54, 95 percent confidence
      interval: 0.31, 0.97). In contrast, women with an abortion history who conceived
      with a new partner had the same risk of preeclampsia as women without a history
      of abortion (adjusted odds ratio = 1.03, 95 percent confidence interval: 0.72,
      1.47). Thus, the protective effect of a prior abortion operated only among women
      who conceived again with the same partner. An immune-based etiologic mechanism is
      proposed, whereby prolonged exposure to fetal antigens from a previous pregnancy
      protects against preeclampsia in a subsequent pregnancy with the same father.

PMID- 12796048
TI  - Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in
      a prospective study.
AB  - Case-control studies suggest that meat and cholesterol intakes may be related to
      elevated risks of pancreatic cancer. Few prospective studies have examined
      associations between diet and pancreatic cancer, although in one recent study
      saturated fat consumption was related to higher risk. In a cohort of US women,
      the authors confirmed 178 pancreatic cancer cases over 18 years of follow-up. A
      mailed 61-item food frequency questionnaire was self-administered at baseline,
      and health and lifestyle variables were updated biennially. Analyses were
      performed using Cox proportional hazards models to adjust for potential
      confounders. Intakes of total fat, different types of fats, and cholesterol were
      not associated with pancreatic cancer risk. Similarly, total meat, red meat, and
      dairy products were not related to risk. Individual food items contributing to
      intakes of total meat and dairy products, as well as fish and eggs, did not
      reveal any specific association. Updating dietary exposures by using
      questionnaires from 1980, 1984, 1986, and 1990 produced similar findings. The
      authors' data do not support previous findings that meat or saturated fat intakes
      are related to pancreatic cancer risk. Future prospective studies should examine
      the influence of cooking practices as well as other dietary habits on the risk of
      pancreatic cancer.

PMID- 12796049
TI  - Lung recruitment in real time: learning was never so easy.

PMID- 12796050
TI  - Eosinophils and interleukin-5: the debate continues.

PMID- 12796051
TI  - From clinical and pathologic to molecular staging of lung cancer.

PMID- 12796052
TI  - To clot or not to clot, that is the question in pulmonary fibrosis.

PMID- 12796053
TI  - A meta-analysis derivation of continuous likelihood ratios for diagnosing pleural
      fluid exudates.

PMID- 12796054
TI  - Superoxide dismutases in the lung and human lung diseases.
AB  - The lungs are directly exposed to higher oxygen concentrations than most other
      tissues. Increased oxidative stress is a significant part of the pathogenesis of
      obstructive lung diseases such as asthma and chronic obstructive pulmonary
      disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung
      granulomatous diseases), and lung malignancies. Lung tissue is protected against
      these oxidants by a variety of antioxidant mechanisms among which the superoxide
      dismutases (SODs) are the only ones converting superoxide radicals to hydrogen
      peroxide. There are three SODs: cytosolic copper-zinc, mitochondrial manganese,
      and extracellular SODs. These enzymes have specific distributions and functions.
      Their importance in protecting lung tissue has been confirmed in transgenic and
      knockout animal studies. Relatively few studies have been conducted on these
      enzymes in the normal human lung or in human lung diseases. Most human studies
      suggest that there is induction of manganese SOD and, possibly, extracellular SOD
      during inflammatory, but not fibrotic, phases of parenchymal lung diseases and
      that both copper-zinc SOD and manganese SOD may be downregulated in asthmatic
      airways. Many previous antioxidant therapies have been disappointing, but newly
      characterized SOD mimetics are being shown to protect against oxidant-related
      lung disorders in animal models.

PMID- 12796056
TI  - Questions about ARDSNetwork trial of low tidal volume.

PMID- 12796055
TI  - Absence of deep inspiration-induced bronchoprotection against inhaled allergen.
AB  - Deep inspiration-induced bronchoprotection appears to be a major mechanism
      through which airway obstruction by spasmogens is avoided. Loss of
      bronchoprotection is associated with airway hyper-responsiveness. Individuals
      with allergic rhinitis and no airway hyperresponsiveness develop obstruction
      after allergen inhalation. To test the hypothesis that deep inspiration-induced
      bronchoprotection is not active against allergic reactions, we performed four
      single-dose bronchial challenges, two with methacholine and two with allergen, on
      10 subjects with allergic rhinitis. Without deep inspirations, the methacholine
      induced reduction in FEV1 from baseline was 36.9 +/- 3.6% (mean +/- SEM); this
      was attenuated to 15.0 +/- 2.0 when five deep inspirations preceded methacholine
      inhalation (p = 0.0001). When allergen was inhaled, the reduction in FEV1 was
      24.7 +/- 2.9% and 28.8 +/- 6.4% without and with deep inspirations, respectively.
      We conclude that bronchoprotection by deep inspirations is absent against
      allergic reactions. Understanding the cause of this phenomenon may shed light
      into the pathogenesis of airway hyperresponsiveness in allergic asthma.

PMID- 12796057
TI  - Mechanical ventilation in patients with pulmonary fibrosis.

PMID- 12796058
TI  - Nitric oxide and tuberculosis infection.

PMID- 12796060
TI  - A ripe old age.

PMID- 12796061
TI  - Duration of anticoagulation in venous thromboembolism.

PMID- 12796062
TI  - Results of ALLHAT: is this the final answer regarding initial antihypertensive
      drug therapy?

PMID- 12796063
TI  - On the value of an old dress code in the new millennium.

PMID- 12796064
TI  - The incidence of recurrent venous thromboembolism after treatment with vitamin K
      antagonists in relation to time since first event: a meta-analysis.
AB  - BACKGROUND: After a first episode of venous thromboembolism, patients are treated
      with vitamin K (phytonadione) antagonists. There are indications that the risk of
      recurrence after treatment with vitamin K antagonists decreases relative to the
      time since the first event. The aim of the present meta-analysis is to describe
      the risk of recurrent venous thromboembolism after treatment with vitamin K
      antagonist in relation to the time since the index event. METHODS: Computerized
      searches in MEDLINE and EMBASE databases; reference checks of pertinent articles;
      personal communication with colleagues to find randomized clinical trials and
      cohort studies in which patients with venous thromboembolism were treated with
      vitamin K antagonists. Per treatment arm, 2 reviewers independently extracted
      data on the number of recurrent events and the duration of follow-up per time
      period of 3 months. RESULTS: A total of 135 potentially eligible studies were
      identified. Of these, 18 studies could be included, comprising 25 treatment arms
      that could be analyzed. Treatment arms were divided into 3 groups based on
      treatment duration (short, medium, and long). For all 3 groups, the monthly
      incidence immediately after discontinuation of treatment was high and declined
      rapidly thereafter. The monthly incidence after 9 months seemed independent of
      the treatment duration. CONCLUSIONS: There is a diminishing risk of recurrent
      venous thromboembolism over time and a stabilization after 9 months independent
      of the duration of the initial treatment with vitamin K antagonists. These
      findings have important implications for decision making about the optimal
      duration of treatment with vitamin K antagonists.

PMID- 12796065
TI  - Interactions between the renin-angiotensin system and dyslipidemia: relevance in
      the therapy of hypertension and coronary heart disease.
AB  - Dyslipidemia and hypertension are frequently observed in patients with ischemic
      heart disease. Studies from a number of laboratories suggest up-regulation of
      different components of the renin-angiotensin system (RAS) in patients with
      hypertension and atherosclerosis. Lipid accumulation in the blood vessels
      enhances the expression of RAS components; on the other hand, activation of RAS
      stimulates accumulation of low-density lipoproteins, particularly the oxidatively
      modified form, in the blood vessels. This concept of cross-talk between
      dyslipidemia and RAS activation has been proven in laboratory-based studies.
      Clinical trials also suggest that blockade of dyslipidemia and RAS may have a
      synergistic salutary effect on the outcome of patients with hypertension and/or
      manifestations of atherosclerosis. This concept needs to be evaluated in large
      clinical studies.

PMID- 12796066
TI  - Clinical significance, pathogenesis, and management of postprandial
      hyperglycemia.
AB  - It is well established that strict glycemic control (hemoglobin A1c <7.0%) can
      prevent the microvascular complications of diabetes mellitus. Recent studies
      indicate that elevated plasma glucose concentrations are an independent and
      clinically significant risk factor for cardiovascular disease in nondiabetic and
      diabetic individuals. Thus, isolated postprandial hyperglycemia (2-hour
      postprandial glucose level >140 mg/dL [>7.8 mmol/L]) in the face of normal
      fasting plasma glucose (<110 mg/dL [<6.1 mmol/L]) and normal hemoglobin A1c
      (<6.1%) values is associated with a 2-fold increased risk of death from
      cardiovascular disease. These observations imply that more strict glycemic
      control is required to prevent macrovascular disease than microvascular disease.
      This review summarizes epidemiologic and experimental studies linking
      postprandial hyperglycemia to cardiovascular disease and therapeutic approaches
      available and in development to treat this disorder.

PMID- 12796067
TI  - Restricted activity and functional decline among community-living older persons.
AB  - BACKGROUND: Restricted activity is common among community-living older persons,
      but its prognostic significance is not known. We performed a prospective cohort
      study to evaluate the association between the occurrence of restricted activity
      and functional decline over an 18-month period. METHODS: We studied 680 community
      living persons, 70 years or older, who were categorized into 3 groups according
      to their risk for disability (low, intermediate, or high) in activities of daily
      living (ADL). Participants were subsequently followed up with monthly telephone
      interviews to ascertain the occurrence of restricted activity, defined as having
      stayed in bed for at least half a day and/or having cut down on their usual
      activities due to an illness, injury, or other problem in the past month.
      Functional decline was defined as an increase in ADL disability scores between
      the baseline and 18-month follow-up assessments, which were completed in the
      home. RESULTS: After adjusting for the baseline risk of disability and other
      covariates, the disability score at 18 months increased (ie, worsened) by 11.2%
      (95% confidence interval [CI], 7.0%-15.6%) for each additional month with
      restricted activity. The association between restricted activity and functional
      decline differed significantly by risk group (P<.001). For the low- and
      intermediate-risk groups, the adjusted disability scores increased by 18.7% (95%
      CI, 10.3%-27.8%) and 7.5% (95% CI, 2.7%-12.5%), respectively, for each additional
      month with restricted activity. There was no association between restricted
      activity and functional decline in the high-risk group, as evidenced by a
      nonsignificant increase in the adjusted disability score of 2.7% (95% CI, -6.6%
      to 12.9%). CONCLUSION: For older persons who are not otherwise at high risk for
      ADL disability, restricted activity is an important predictor of functional
      decline and not just a benign feature of old age.

PMID- 12796068
TI  - The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam
      Study.
AB  - BACKGROUND: Epidemiologic studies have shown that C-reactive protein (CRP) is a
      risk factor for coronary heart disease. Whether routine measurement of CRP has a
      role in the prediction of future coronary disease in everyday clinical practice
      has not yet been investigated. METHODS: Within the Rotterdam Study, a population
      based cohort study of 7983 men and women 55 years and older, we conducted a
      nested case-control study to investigate the value of CRP in coronary disease
      prediction. Data are based on 157 participants who experienced a myocardial
      infarction during follow-up and 500 randomly selected controls. High-sensitivity
      CRP and traditional cardiovascular risk factors were measured at baseline.
      RESULTS: The age- and sex-adjusted relative risk of myocardial infarction for
      subjects in the highest quartile of the population distribution of CRP compared
      with the lowest quartile was 2.0 (95% confidence interval, 1.1-3.4). After
      additional adjustment for traditional cardiovascular risk factors, the increase
      in risk largely disappeared (odds ratio, 1.2; 95% confidence interval, 0.6-2.2).
      Adding CRP to a coronary disease risk function based on risk factors that are
      routinely assessed in clinical practice or to the Framingham risk function did
      not improve the area under the receiver operating characteristic curve of these
      risk functions. Sensitivity and specificity of both risk functions, computed
      after dichotomizing the estimated disease probabilities using prespecified cutoff
      points, hardly improved when CRP was added. CONCLUSION: Measurement of CRP in
      elderly people has no additional value in coronary disease risk prediction when
      traditional cardiovascular risk factors are known.

PMID- 12796069
TI  - Alcohol drinking patterns and risk of type 2 diabetes mellitus among younger
      women.
AB  - OBJECTIVE: To examine the relationship between alcohol consumption and the
      incidence of type 2 diabetes mellitus among relatively young and middle-aged
      women. METHODS: In a prospective study, 109 690 women, aged 25 to 42 years,
      without a history of coronary heart disease, stroke, cancer, or diabetes mellitus
      completed a detailed lifestyle and medical history questionnaire in 1989. During
      10 years of follow-up, we documented 935 incident cases of type 2 diabetes
      mellitus. RESULTS: We found a nonlinear relationship between alcohol consumption
      and risk of type 2 diabetes mellitus after adjustment for multiple confounders,
      including body mass index, smoking, physical activity, and family history of
      diabetes mellitus (quadratic trend P =.003). Compared with lifelong abstainers,
      the adjusted relative risks (95% confidence intervals) were 0.80 (0.66-0.96) for
      those consuming 0.1 to 4.9 g/d, 0.67 (0.50-0.89) for those consuming 5.0 to 14.9
      g/d, 0.42 (0.20-0.90) for those consuming 15.0 to 29.9 g/d, and 0.78 (0.34-1.78)
      for those consuming 30.0 g/d or more. Further adjustment for dietary factors,
      including glycemic load, trans-fatty acid, polyunsaturated fat, and total fiber
      intake, did not appreciably alter these findings. The inverse association with
      light to moderate drinking was most apparent in women who reported wine or beer
      drinking. Women who reported 30.0 g/d or more of liquor intake showed a
      significantly increased risk of diabetes mellitus compared with those who did not
      report liquor intake (adjusted relative risk, 2.50; 95% confidence interval, 1.00
      6.23). CONCLUSION: Light to moderate alcoholic beverage consumption may be
      associated with a lower risk of type 2 diabetes mellitus among women aged 25 to
      42 years, although this benefit may not persist at higher levels.

PMID- 12796070
TI  - Duration of prophylaxis against venous thromboembolism with fondaparinux after
      hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind
      study.
AB  - BACKGROUND: The benefit of thromboprophylaxis for 1 month has never been
      evaluated in patients undergoing hip fracture surgery, a setting in the highest
      risk category for postoperative venous thromboembolism (VTE). METHODS: In a
      double-blind multicenter trial, 656 patients undergoing hip fracture surgery were
      randomly assigned to receive prophylaxis with a once-daily subcutaneous injection
      of either 2.5 mg of fondaparinux sodium or placebo for 19 to 23 days. Before
      randomization, all patients had received fondaparinux for 6 to 8 days. The
      primary efficacy outcome was VTE occurring during the double-blind period (deep
      vein thrombosis detected by mandatory bilateral venography or documented
      symptomatic deep vein thrombosis or pulmonary embolism). The main safety outcome
      was major bleeding. RESULTS: The primary efficacy outcome was assessed in 428
      patients. Fondaparinux reduced the incidence of VTE compared with placebo from
      35.0% (77/220) to 1.4% (3/208), with a relative reduction in risk of 95.9% (95%
      confidence interval, 87.2%-99.7%; P<.001). Similarly, the incidence of
      symptomatic VTE was significantly lower with fondaparinux (1/326; 0.3%) than with
      placebo (9/330; 2.7%). The relative reduction in risk was 88.8% (P =.02).
      Although there was a trend toward more major bleeding in the fondaparinux group
      than in the placebo group (P =.06), there were no differences between the 2
      groups in the incidence of clinically relevant bleeding (leading to death,
      reoperation, or critical organ bleeding). CONCLUSIONS: Extended prophylaxis with
      fondaparinux for 3 weeks after hip fracture surgery reduced the risk of VTE by
      96% and was well tolerated.

PMID- 12796072
TI  - Percutaneous endoscopic gastrostomy does not prolong survival in patients with
      dementia.
AB  - BACKGROUND: Artificial feeding by a percutaneous endoscopic gastrostomy (PEG)
      tube in patients with dementia has increased since the introduction of the
      endoscopic method of tube placement. Few studies have documented survival benefit
      from this intervention. This report reviews our experience with PEG tube
      placement for feeding patients with dementia. METHODS: All consultations for PEG
      tube placement were evaluated by a certified nutrition support nurse (L.M.M.) in
      consultation with a member of the gastroenterology physician staff (T.O.L.) for
      24 months. Evaluation included the attainment of a brief medical history, a
      physical examination, and a review of comorbid conditions, laboratory variables
      for nutrition status, and bleeding risk. Interviews with patients or surrogates
      were conducted, including an explanation of the risks and benefits of PEG tube
      placement. A Kaplan-Meier survival curve was used to compare the median survival
      between patients with dementia who received a PEG tube and patients with dementia
      in whom PEG tube placement was refused. RESULTS: We received 41 consultations for
      PEG tube placement in patients with dementia. Percutaneous endoscopic gastrostomy
      was performed in 23 patients; 18 patients met the medical criteria for PEG tube
      placement, but surrogates refused placement. The median survival for the 23
      patients who underwent PEG was 59 days; the median survival for the 18 patients
      who did not undergo PEG was 60 days. CONCLUSION: There seems to be no survival
      benefit in patients with dementia who receive artificial feeding by a PEG tube.

PMID- 12796071
TI  - Effects of a 16-month randomized controlled exercise trial on body weight and
      composition in young, overweight men and women: the Midwest Exercise Trial.
AB  - BACKGROUND: In light of the current obesity epidemic, treatment models are needed
      that can prevent weight gain or provide weight loss. We examined the long-term
      effects of a supervised program of moderate-intensity exercise on body weight and
      composition in previously sedentary, overweight and moderately obese men and
      women. We hypothesized that a 16-month program of verified exercise would prevent
      weight gain or provide weight loss in the exercise group compared with controls.
      METHODS: This was a randomized controlled efficacy trial. Participants were
      recruited from 2 midwestern universities and their surrounding communities. One
      hundred thirty-one participants were randomized to exercise or control groups,
      and 74 completed the intervention and all laboratory testing. Exercise was
      supervised, and the level of energy expenditure of exercise was measured.
      Controls remained sedentary. All participants maintained ad libitum diets.
      RESULTS: Exercise prevented weight gain in women and produced weight loss in men.
      Men in the exercise group had significant mean +/- SD decreases in weight (5.2 +/
      4.7 kg), body mass index (calculated as weight in kilograms divided by the
      square of height in meters) (1.6 +/- 1.4), and fat mass (4.9 +/- 4.4 kg) compared
      with controls. Women in the exercise group maintained baseline weight, body mass
      index, and fat mass, and controls showed significant mean +/- SD increases in
      body mass index (1.1 +/- 2.0), weight (2.9 +/- 5.5 kg), and fat mass (2.1 +/- 4.8
      kg) at 16 months. No significant changes occurred in fat-free mass in either men
      or women; however, both had significantly reduced visceral fat. CONCLUSIONS:
      Moderate-intensity exercise sustained for 16 months is effective for weight
      management in young adults.

PMID- 12796073
TI  - Continuity of care and recognition of diabetes, hypertension, and
      hypercholesterolemia.
AB  - BACKGROUND: Continuity of care has been shown to have a variety of health
      benefits, but the effect of continuity of care on recognition of common chronic
      diseases has been underinvestigated. OBJECTIVE: To examine the relationship
      between continuity of care and the recognition of 3 prevalent chronic diseases:
      diabetes, hypertension, and hypercholesterolemia. METHODS: We analyzed data from
      the third National Health and Nutrition Examination Survey, a nationally
      representative sample of 18 162 adult noninstitutionalized residents of the
      United States collected from 1988 through 1994. We examined the proportion of
      unrecognized disease among all individuals with diabetes, hypertension, and
      hypercholesterolemia according to self-reported level of continuity of care. We
      used logistic regression to control for possible confounders, including number of
      disease risk factors. RESULTS: Among persons with diabetes, in adjusted models,
      those with a usual provider of care had a lower likelihood of having unrecognized
      disease (odds ratio, 0.30; 95% confidence interval, 0.10-0.95) than those with no
      usual site or provider of care. Unrecognized hypertension had an unadjusted
      relationship with level of continuity of care, but continuity of care was not a
      significant predictor after possible confounders were adjusted for. Unrecognized
      hypercholesterolemia was not predicted by level of continuity of care.
      CONCLUSIONS: Continuity of care has some benefits in terms of recognizing chronic
      disease, although benefits appear to be disease specific. More research needs to
      be conducted to elucidate the complex relationship between continuity and disease
      recognition.

PMID- 12796074
TI  - Reduction of out-of-hospital symptomatic venous thromboembolism by extended
      thromboprophylaxis with low-molecular-weight heparin following elective hip
      arthroplasty: a systematic review.
AB  - BACKGROUND: Numerous trials and meta-analyses have shown that extended out-of
      hospital prophylaxis with low-molecular-weight heparin reduces asymptomatic and
      symptomatic venous thromboembolism after total hip arthroplasty. We hypothesized
      that knowledge of the results of screening tests may have resulted in
      overdiagnosis of symptomatic venous thromboembolism in many of these studies. The
      purpose of this analysis was to obtain an accurate estimate of the absolute risk
      reduction (ARR) of symptomatic venous thromboembolism after discharge from
      hospital in controlled studies that avoided this potential bias for
      overdiagnosis. METHODS: Articles were identified using MEDLINE, EMBASE, and the
      Cochrane Library databases (January 1980-April 2002). Studies were eligible if
      the assessment of symptomatic venous thromboembolism was standardized and
      performed independently of mandatory objective testing. RESULTS: Two studies (907
      patients) were eligible for assessment of symptomatic venous thromboembolism, 5
      studies (1917 patients) for symptomatic pulmonary embolism, and 7 studies (2425
      patients) for fatal pulmonary embolism. In controls vs extended treatment groups,
      after hospital discharge, the frequency of symptomatic venous thromboembolism was
      2.7% vs 1.1% (ARR, 1.56%; 95% confidence interval [CI], -0.21% to 3.3%; number
      needed to treat, 64); symptomatic pulmonary embolism was 0.36% vs 0% (ARR, 0.36%;
      95% CI, -0.3% to 1.36%; number needed to treat, 278); and fatal pulmonary
      embolism was 0.09% vs 0% (ARR, 0.09%; 95% CI, -0.08% to 0.27%; number needed to
      treat, 1093). CONCLUSIONS: The absolute reduction in symptomatic venous
      thromboembolism attributed to extended prophylaxis in some studies and meta
      analyses seems to have been overestimated.

PMID- 12796075
TI  - Raloxifene causing malabsorption of levothyroxine.
AB  - To our knowledge, raloxifene hydrochloride, a selective estrogen receptor
      modulator, has never been reported to interfere with absorption of levothyroxine.
      We describe a 79-year-old woman with chronic, treated primary hypothyroidism,
      presenting with increasing levothyroxine requirement while taking raloxifene at
      the same time as levothyroxine. For two 6- to 8-week periods, we separated the
      ingestion of raloxifene and levothyroxine by about 12 hours. In addition, we
      tested the absorption of 1.0 mg of levothyroxine sodium with and without the
      coadministration of 60 mg of raloxifene hydrochloride on 2 separate occasions by
      collecting serial blood samples for 6 hours. Hypothyroidism occurred in a
      reproducible fashion whenever levothyroxine and raloxifene were administered
      together and improved whenever they were taken separately. Combined
      administration of levothyroxine and raloxifene resulted in lower levels of serum
      thyroxine compared with administration of levothyroxine alone. By a yet unknown
      mechanism, raloxifene caused malabsorption of levothyroxine in our patient when
      coadministered.

PMID- 12796076
TI  - Eosinophilia and diseases: clinical revision of 1862 cases.

PMID- 12796077
TI  - Herb-drug interactions: survey of leading pharmaceutical/herbal companies.

PMID- 12796078
TI  - Sleep duration and disease.

PMID- 12796079
TI  - To sleep, perchance to increase the risk of coronary events.

PMID- 12796080
TI  - Irritable bowel syndrome: new recommendations for diagnosis and treatment.

PMID- 12796081
TI  - Naproxen's interaction with aspirin may affect its cardioprotective effect.

PMID- 12796084
TI  - Structural explanation in chemistry and its evolving forms.
AB  - Historically, there has been a close relationship between the concepts of
      structure and of shape. Is the relationship a matter of fact or is it conceptual?
      Exploring this question with examples enables us to distinguish several senses of
      structure. Clearly, spatial shape is not conceptually related to constitutive
      structure, since a molecule may consist only of an ordered set of potentialities.
      The concept of structure in chemistry developed in the nineteenth century from an
      ambiguous but essentially taxonomic use in type theory to a realist hypothesis as
      to the spatial distribution of atoms in the molecule. This development required a
      defense of the Daltonian view of elements as constituted by minute corpuscularian
      atoms. Once a realist concept of structure had been established, the issue of the
      nature of structural explanation could then be addressed. Template explanation
      formats as well as jigsaw formats can be found in chemistry. The problem of
      halting a regress of structural explanations leads to a sketch of a way in which
      physics can serve as a heterogeneous foundation for chemistry without
      reductionist implications.

PMID- 12796085
TI  - Explaining explanation in chemistry.
AB  - The notion that explanations are arguments, central to the covering law account,
      persists in developments of accounts of explanation in general philosophy of
      science. I argue that these developments fail to capture chemical explanation
      motivating the explanatory autonomy of chemistry requires the investigation of
      alternative accounts. Ubiquitous use of models in chemistry is indicative of
      their importance to explanation. I argue that contemporary accounts of models
      that emphasize their partial autonomy from fundamental physical laws provide a
      basis for investigating explanation in chemistry. Furthermore, I sketch the
      importance of the semantic view of theories in articulating model autonomy, and
      thus why the semantic view might fulfill a significant role in explicating the
      explanatory autonomy of chemistry.

PMID- 12796086
TI  - On explanatory practice and disciplinary identity.
AB  - This essay explores connections between explanatory discourse and disciplinary
      identity. While explanation is frequently assumed to be one of the central aims
      of the sciences, I contend that if we want to appreciate explanation's role
      within scientific practice, we need to look elsewhere. Explanations encode the
      aims and values of particular scientific communities, telling practitioners what
      they should want to know about the world and how they should reason to get there.
      By inculcating patterns of reasoning consistent with these aims and values,
      explanatory discourse is crucial for the formation of cohesive scientific
      disciplines. Yet because such discourse is frequently grounded in exemplars, the
      implicit nature of exemplar-based training must be confronted. I argue that
      exemplars are an appropriate vehicle for communicating skill-based knowledge and
      methodological norms and, additionally, that exemplars are a practical means of
      grappling with the indeterminacy of theory application.

PMID- 12796087
TI  - The ignis fatuus of reduction and unification: back to the rough ground.
AB  - Given the enormous variety of possible intertheoretical relations, the
      proliferation of definitions of reduction, supervenience, emergence, unification,
      and so on, as well as the fact that empirical studies have provided support for
      almost any metaphysical option or, alternatively, have shown rather conclusively
      that empirically the case is inconclusive, I suggest a moratorium on the use of
      words such as "reduction," "supervenience," and "unification" and to go back to
      the rough ground and give perspicuous renderings of the practice of chemistry.
      What is needed are very detailed case studies and further discussions about them,
      instead of bickering about whether chemistry can be reduced to physics,
      supervenes on it, can be unified with it, and similar "metaphysical" concerns.

PMID- 12796088
TI  - Autonomy, explanation, and theoretical values: physicists and chemists on
      molecular quantum mechanics.
AB  - The emergence of quantum chemistry in the early twentieth century was an
      international as well as an interdisciplinary affair, involving dialogue between
      physicists and chemists in Germany, the United States, and Britain. Historians of
      science have recently documented both the causes and effects of this
      internationalism and interdisciplinarity. Chemists and physicists involved in the
      development of quantum chemistry in its first few decades tended to argue for
      opposing views on acceptable standards of explanation in their field, although
      the debate did not divide along disciplinary lines. The purpose of this paper is
      to investigate these different positions, through the methodological reflections
      of John Clarke Slater, Linus Pauling, and Charles Coulson. Slater tended to argue
      for quantum-mechanical rigor and the application of fundamental principles as the
      values guiding models of molecular bonding. Although they were on different sides
      of the debate between the valence-bond and molecular-orbital approaches, Pauling
      and Coulson both emphasized the recovery of traditional chemical explanations and
      systematic explanatory power within chemistry.

PMID- 12796089
TI  - Natural kinds, explanation, and essentialism in chemistry.
AB  - The problem of natural kinds in chemistry is analyzed, proceeding mainly from Rom
      Harre's and Jaap van Brakel's writings. The problem of natural kinds proves to be
      different in general philosophy and in philosophy of science. This problem, which
      originally emerged at the borderline of science and philosophy, belongs to the
      domain of philosophy of science. Philosophy in general cannot hope that
      scientific knowledge will help to explain philosophical issues. Chemistry has to
      be taken very seriously in philosophy of science. Not only do empirical arguments
      indicate that chemistry should be regarded as a typical science, but it is also
      relevant for elaborating a theoretical model of science. Chemistry as the science
      of substances is well suited for the philosophical analysis of the role of the
      concept of natural kinds in science. The viability of the concept of a natural
      kind in philosophy of chemistry derives from the explanatory role of chemical
      natural kinds. The problem of explanation in its turn relates natural kinds to
      the laws of nature and scientific theories, that is, to classical issues in
      philosophy of science and to discussions on their (supposed) specificity in
      chemistry. In philosophy of science, one can demonstrate that there exists a
      third option between metaphysical realism and internal realism (to use Putnam's
      terminology). According to this third type of realism our "world versions"
      (including natural kinds identified by us), but not the world itself, are
      relative to us.

PMID- 12796090
TI  - The primary properties?
AB  - Science is concerned not just with objects but also with their various aspects,
      such as their colors, temperatures, sizes, and shapes. These aspects, or
      properties, are generally thought to be of at least two kinds: primary
      properties, such as shape, size, and motion and secondary ones, such as
      temperature and color. However, there is little agreement on just what the
      difference is between these two kinds of properties. An argument has recently
      been put forth that assumes the two kinds of properties differ only in that the
      secondary ones are dependent on the conditions under which they are observed.
      This paper suggests, however, that since the primary properties depend on
      conditions, too, any argument based on this assumption is flawed. There are two
      main traditional accounts of the distinction. The first account of the
      distinction-the ideas of primary qualities resemble the properties that cause
      these ideas, whereas those of the secondary ones do not resemble them-relies on
      what to many is an implausible assumption, that some of our ideas resemble
      features of the world and we can speak intelligibly about such resemblances. This
      paper suggests that we cannot, and hence we have no more reason to believe that
      the ideas of the primary qualities resemble aspects of the world than we do that
      those of the secondary qualities do so. The second traditional account-primary
      properties are those a body has, however small it might be, whereas secondary
      properties are a consequence just of relations between bodies-fares better than
      the other two accounts. However, the notion of force posed a serious problem for
      this second basis for the distinction, one that has, astonishingly, hardly found
      its way into the philosophical literature.

PMID- 12796091
TI  - Varieties of properties: an alternative distinction among qualities.
AB  - The traditional distinction between primary (observation independent) and
      secondary (observation dependent) qualities is not based on a difference that can
      be sustained in the full light of contemporary scientific understanding. An
      alternative division of physical and chemical properties is proposed. Like the
      traditional division of qualities, the alternative system has two main
      categories. Properties of compound particulars that result from simple
      combination (e.g., addition) of the properties of their component parts
      constitute the first class: properties that depend on details of interactions
      between component parts (e.g. cooperative effects) make up the second type.
      Application of the alternative dichotomy is considered for the cases of mass
      (traditionally a primary property) and color (a secondary quality, in the usual
      division). Both these types of properties can fall in either of the two classes
      of the alternate division of qualities, depending on the nature of the
      interaction that occurs between components. Both mass and color show that
      intermediate cases occur. Application of the alternative categorical scheme is
      straightforward, but not always simple. The proposed system shows that in
      chemical combination (and, perforce, in the many more complex systems common in
      human culture) interactions profoundly influence properties of entities that
      enter the interaction. This is not adequately treated by philosophical theories
      of wholes and parts (mereology), which should be extended to apply to such
      important cases.

PMID- 12796092
TI  - Property reduction in chemistry: some lessons.
AB  - By taking molecules and atoms as models for wholes and parts, I explore the
      relation between the atomic and molecular properties in this article. Molecular
      properties do not reduce to atomic properties in the sense the former cannot be
      obtained by adding or multiplying the latter. However, quantum states of
      molecules are obtained from the quantum states of atoms by addition and
      multiplication. Because molecular properties are calculated reliably from the
      atomic states in quantum theory, it may be claimed that property reduction has
      been accomplished successfully. I show that such reduction entails underlying
      holism.

PMID- 12796093
TI  - Chemical substances and intensive properties.
AB  - Despite the importance molecular structure has acquired in 20th century
      chemistry, more traditional macroscopic notions in terms of a continuous concept
      of matter continue to play a role in chemical theorizing. In the light of the
      extensive and determined criticism of reductionism in recent philosophy of
      chemistry, it is of interest to see macroscopic ontology treated autonomously.
      One aspect of this is developed here, namely, the concept of chemical substance.
      This is characterized by contrast with phases and solutions. The key conception
      is that of an intensive property, which is defined by appeal to the mereological
      structure of parts of the entities bearing substance properties.

PMID- 12796094
TI  - Paradoxes of measurement.
AB  - Applying Husserl's Eidetic Phenomenology to the transcendental structure (or
      "phenomenological reduction") of scientific data "given" in measurement to a
      first-person individual observer (the experimenter, S(1)) and a related third
      person individual observer (the observer of the measurement process, S(3)), and
      comparing the outcomes, two paradoxical theses, "paradoxes of measurement," are
      derived. Thesis I: classical science necessarily entails "complementarity,"
      "uncertainty relations," and the "entanglement" of observers and the data they
      observe. This situation is analogous in structure to that of quantum physics.
      Thesis II: a quantum object is a physical object with footprints in the
      perceptual world, but lacking a space-time "body"; it exists ontologically before
      the constitution of the perceptual world of the laboratory.

PMID- 12796095
TI  - Chemical kinetics and dynamics.
AB  - Chemical reactions correspond to irreversible processes creating entropy.
      Chemistry belongs to the class of nonintegrable Poincare systems. In general,
      chemistry is associated with resonances-transitions of quantum states. We have
      studied some very simple examples of such processes, like decay of an unstable
      state, in detail. (In such cases, there are always multiple time scales.) We
      obtain a nonunitary ("star unitary"), invertible, nondistributive operator Lambda
      (which reduces to the unitary transformation operator U for integrable systems).
      The explicit form of Lambda depends on the interaction of each species with all
      other types of molecules in the system including the solvent. The basic property
      that results from Lambda is that the fundamental description of nonintegrable
      systems is no longer in terms of Hamiltonian equations, but in terms of kinetic
      equations with broken time symmetry. Once we have the kinetic equations, it is
      easy to show that we have irreversible processes and entropy production.

PMID- 12796096
TI  - Reaction mechanisms and chemical explanation.
AB  - The methodological and ontological issues arising in the organic chemists'
      explanation of transformations of matter by means of reaction mechanisms are
      presented based on the general view that chemistry is at the same time an
      autonomous discipline with its own paradigm and an integral part of the unitary
      body of science. Among the issues relevant to research is the nature and actual
      observability of activated complexes, which have by definition a vanishing
      lifetime. That issue illustrates the interplay of molecular chemistry and quantum
      physics at the submicroscopic level of sensible reality. A moral concerning the
      planning and strategy of research is briefly outlined.

PMID- 12796097
TI  - Explanation in organic chemistry.
AB  - In this paper, a model of a subclass of the explanations given in organic
      chemistry is developed. This model is supported by three concrete examples. The
      model suggests that in this discipline, laws, theories, and causal reasoning are
      interrelated in interesting and heretofore unexplored ways. The model also
      reserves a prominent place for idealizations and capacities ascribed on the basis
      of the structural features of molecules. The author hopes to have established
      that philosophical reflection on the methodology of organic chemistry can yield
      interesting and valuable new insights into classical issues in the philosophy of
      science.

PMID- 12796098
TI  - On the ordinality of causes in complex autocatalytic systems.
AB  - The convention in chemical dynamics usually is to identify the reactant and
      catalytic molecules as the active agencies that combine in mechanical fashion to
      constitute a reaction process. When macromolecules grow large and complex enough
      to exhibit some plasticity, however, the subsequent directions in which these
      molecules change may be guided more by the nexus of chemical reactions in which
      they participate. In particular, configurations of autocatalytic reactions among
      plastic macromolecules can come to exert more agency upon the component reactants
      and mechanisms than vice versa, and the nexus of such processes retains its
      identity longer than do the latter, more transient participants. Whence, the
      ascendancy of autocatalytic forms as causal agencies provides a natural example
      of the phenomenon of "emergence" and affords a way out of the conundrums that
      currently obfuscate the issue of the origin of life.

PMID- 12796099
TI  - Chirality and handedness: the Ruch "shoe-potato" dichotomy in the right-left
      classification problem.
AB  - Chirality and handedness are concepts that apply to the structure of molecules.
      Chirality is defined by the lack of certain features of symmetry, which lead to
      an object not being superimposable on its mirror image. Handedness is a different
      phenomenon relating to the ability to classify chiral objects into right-handed
      and left-handed objects. All handed objects are chiral, but not all chiral
      objects are handed. In 1968 through 1970, Ruch and coworkers developed a theory
      of chirality that provided a mathematical basis for the handedness of chiral
      objects. Handed chiral objects are considered to be analogous to shoes, which are
      readily classified into right and left shoes regardless of the size, material,
      style, or other attributes of the shoes in question. Nonhanded chiral objects are
      considered to be analogous to potatoes, which have no symmetry because of their
      irregular patterns of "bumps" and "eyes," thereby meeting the lack of symmetry
      requirements for chirality. There is, however, no unambiguous way to classify a
      set of potatoes into "left" and "right" potatoes. In the case of molecules, a
      tetrahedron with four different substituents such as an asymmetric carbon atom in
      organic chemistry can readily be classified into right and left tetrahedra, as is
      typical for organic molecules in biological systems. An octahedral molecule with
      six different substituents, however, exhibits nonhanded chirality. For this
      reason, the fact that the key building block of natural products is a tetrahedral
      carbon atom rather than an octahedral atom of some type may be a critical factor
      in the handedness of many molecules found in biological structures.

PMID- 12796100
TI  - How harmful is the first law?
AB  - In his First Law (of thermodynamics), Clausius emphasized the equivalence of heat
      and work-conservation of energy was mentioned only indirectly. Today, the main
      emphasis is put on energy conservation, but the equivalence of heat and work has
      proven not only to be superfluous, but also highly destructive. Because of this
      emphasis, heat is no longer considered an independent entity. In the guise of the
      quantity Q heat acts in a strange double role-an entity equivalent to work, but
      also as something fundamentally different. The place formerly occupied by heat is
      now filled with an abstract quantity, the entropy S-a phantom without
      macroscopically relevant properties. By using a phenomenological approach to
      entropy, it can be shown that entropy S does indeed have easily comprehensible
      macroscopic properties. This approach can be used to simplify thermodynamic
      reasoning and to reduce the calculus of thermodynamics to a fraction of its usual
      extent.

PMID- 12796101
TI  - Physical explanation of the periodic table.
AB  - The Periodic Table of the elements, the most important generalization in
      chemistry, is often considered as a representative special case in the study of
      the relation between chemistry and physics. Its quantum interpretation was
      initiated, but not completed, by Niels Bohr. In this paper, post-Bohr conceptual
      developments are discussed from historical and epistemological points of view.
      The difference between high-precision numerical calculations for individual atoms
      and the theory of the periodic system as a whole is emphasized. Periodic laws met
      in Nature are not restricted to the chemical Periodic Table. A comparative study
      of these laws makes it possible to single out essential features that define the
      particular pattern of periodicity. It is shown that the periodic system of
      neutral ground state atoms now has a firm nonempirical quantum-theoretical basis.
      Alternative approaches, based on group theory and other mathematical schemes, are
      briefly discussed. It is argued that, while quantum theory is capable of fully
      accurate calculations for relatively simple atoms or molecular objects, the
      complexity of polyatomic molecules and chemical reactions guarantees the
      flourishing of chemistry as a separate scientific discipline.

PMID- 12796102
TI  - Gauge theory and chemical structure.
AB  - The possibility of chemical structure in the context of quantized matter is
      examined by way of Richard Bader's Atoms in Molecules. I critically examine his
      notion of "electronic charge density"-showing that he cannot really mean "density
      of charge"-and I argue that the appropriate concept is expectation value of
      charge. This still allows him to define chemical structure, but it makes
      problematic his appeals to the explanatory power of structure. This is because,
      as Rosenfeld and Bohr showed, the expectation value of charge cannot be taken as
      the electronic field experienced by other charges. I suggest that we can recover
      the efficacy of structure by thinking of chemistry as a gauge theory. Current
      consensus in the study of gauge theories indicates that gauge potentials
      represent a new type of property; while no member of the family of functions
      comprising the gauge potential is real, the potential itself is causally potent.
      I illustrate this in the case of electrodynamics, where the vector potential can
      causally influence charges in the absence of electric or magnetic fields. I show
      how chemical structure can be considered to be a gauge field. Following Bader, I
      take it to be a family of geometric configurations, no one of which is possessed
      by a given molecule. I claim that current research in gauge theory licenses the
      attribution of causal potency to this notion of structure, despite its lack of
      reality. I thus begin the process of freeing the explanatory resources of gauge
      theory from physics alone.

PMID- 12796103
TI  - Symmetry in basic physical laws.
AB  - Recent physical experiments suggest that chirality is not a purely chemical
      phenomenon, but seems to be an inherent feature of basic physical laws. A
      fundamental physical principle (the CPT theorem) connects asymmetry in space with
      the "arrow of time," and shows that such an arrow exists even on the level of
      mesons.

PMID- 12796104
TI  - The metaphorical foundations of chemical explanation.
AB  - To address the question of whether typical chemical explanations have
      characteristics that distinguish them from explanations in other sciences, it is
      important to recognize the deeply metaphorical nature of scientific explanation
      in general. The theory of conceptual metaphor, based on results from modern
      cognitive sciences, postulates that largely unconscious thought processes,
      grounded in embodied experience and in experiences drawn from the social domain,
      are at the core of scientific reasoning. I argue, using several examples, that
      models employed by chemists as explanatory instruments are metaphorical in nature
      and have a character distinguishable from explanatory representations employed in
      other fields of science.

PMID- 12796105
TI  - "Causes" in chemical explanations.
AB  - Chemists talk about causes and make frequent use of the verb "to cause." They use
      the verb "to cause" for its generality in identifying causal chains, whether all
      the details of those chains are established or some remain unclear. Most of these
      causal chains bottom out in attractions and repulsions. Attractions and
      repulsions are causal relations that are chemically basic; chemistry has no
      further story to tell about why attraction and repulsion are causal. If there is
      some further story to tell about the causal status of attraction and repulsion,
      it is left to physics to tell it, but it is not obvious that the absence of such
      a story would prevent chemists from using attractions and repulsions in their
      causal explanations.

PMID- 12796106
TI  - John Dalton and the aesthetics of molecular representation.
AB  - This paper examines the negative response to Dalton's symbolism in the context of
      the representational system of affinity tables. When situated in an iconoclastic
      scientific culture that rejected overt speculation, affinity tables reflected a
      functionalist empirical aesthetic, while Dalton's symbols embraced a deductive
      aesthetic suggestive of alchemical iconography.

PMID- 12796108
TI  - Statement analysis in chemistry.
AB  - Close philosophical examination of chemical research reports ("statement
      analysis") can lead to clarification of ambiguities and resolution of logical
      confusions, and also lead to other useful conclusions.

PMID- 12796107
TI  - Writing as thinking.
AB  - In this article I try to sketch preliminary answers to several questions. (1)
      What is the role of writing in science? (2) How can rhetorical analysis
      illuminate the nature of scientific writing? (3) What is the role of models and
      metaphors in scientific thinking and writing? Since this is a preliminary
      inquiry, my remarks are brief and suggestive, but I think they point to some
      profitable directions for further study.

PMID- 12796109
TI  - Beyond the dimensionality of visualization in chemistry.
AB  - This article elaborates a key aspect of applied visualization in chemistry:
      dimensionality. On the one hand, the dimensionality of visualization is
      restricted by the medium of information transfer; on the other hand, several
      techniques make it possible to achieve visualizations of parameters of
      multidimensional objects of chemical research in ways that, in a sense, transcend
      the limits of the physical space-time continuum. Effectiveness of chemistry
      research, as well as of chemical education, requires proper perception of
      parameters of objects being investigated. The appropriate application of
      visualization techniques can be crucial.

PMID- 12796110
TI  - Justifying instrumental techniques of analytical chemistry.
AB  - In this paper, we argue that the foundations of chemistry rely as much on the
      methods of measurement as they do on categories of chemical substance. To some
      degree, chemists perform the work of knowledge engineering: designing complex
      systems for the efficient retrieval of information. Indeed, in some cases,
      methods of instrumental detection move to the forefront of attention. For
      example, researchers are expected to deploy optimization methods designed to
      maximize desired signal and minimize the damaging effects of noise. But in his
      important contributions to the development of high-resolution NMR spectrometers,
      Hans Primas used stochastic methods to reveal beneficial effects of noise for
      characterizing physical systems, demonstrating the value of noisy signals for
      nonlinear physical systems in chemistry.

PMID- 12796111
TI  - Negotiated identities of chemical instrumentation: the case of nuclear magnetic
      resonance spectroscopy, 1956-1969.
AB  - What is an NMR spectrometer? Beginning with this seemingly simple question, I
      will explore the development of nuclear magnetic resonance spectroscopy between
      the years 1956 and 1969 from two vantage points: the organic chemists who used
      the new instrument, and Varian Associates-the makers of the first NMR
      spectrometers-. Through an examination of the articles and advertisements
      published in the Journal of Organic Chemistry, I will draw two conclusions.
      First, organic chemists and Varian Associates (along with other actors) are co
      responsible for the development of nuclear magnetic resonance spectroscopy (i.e.,
      NMR spectroscopy was not created by a single actor). Second, by changing the way
      NMR spectrometers are used, organic chemists attempted to change to the identity
      of the instrument. Similarly, when Varian Associates advertised their NMR
      spectrometers in a different way, they, too, attempted to change the identity of
      the instrument.

PMID- 12796113
TI  - Richard Rufus's theory of mixture: a medieval explanation of chemical
      combination.
AB  - Richard Rufus of Cornwall offered a novel solution to the problem of mixture
      raised by Aristotle. The puzzle is that mixts or mixed bodies (blood, flesh,
      wood, etc.) seem to be unexplainable through logic, even though the world is full
      of them. Rufus's contribution to this long-standing theoretical debate is the
      development of a modal interpretation of certain Averroistic doctrines. Rufus's
      account, which posits that the elemental forms in a mixt are in accidental
      potential, avoids many of the problems that plagued non-atomistic medieval
      theories of mixture. This paper is an initial examination of Rufus' account.

PMID- 12796112
TI  - Chemical versus biological explanations: interdisciplinarity and reductionism in
      the 19th century life sciences.
AB  - This paper analyzes four controversies in the 19th century life sciences: the
      nature of fermentation, the nature of infectious diseases, the generation of life
      from inanimate matter, and vitalism. All these controversies appear to concern
      chemical versus biological explanations, suggesting that reduction of biology to
      chemistry was the common underlying issue. My analysis rejects such
      interpretations, including the labels for explanation, and instead points out
      sophisticated forms of interdisciplinarity between chemistry, medicine, and
      biology in the first three debates. I argue that the philosophically favored
      perspective on reductionism, historically induced by a few physicians in the
      fourth debate, leads us astray from understanding interdisciplinary research.

PMID- 12796114
TI  - The Lavoisier-Kirwan debate and approaches to the evaluation of theories.
AB  - This paper applies concepts proposed by Larry Laudan for evaluation of scientific
      theories to problems that arose for Antoine Lavoisier's oxygen theory during the
      period from 1780 to 1790. Lavoisier's original theory (1779) had an empirical
      problem (why does dilute sulfuric acid produce hydrogen on contact with metals,
      whereas concentrated acid, even when heated, does not?). The solution to this
      puzzle led to a more refined conceptual problem, regarding the overall
      consistency of the theory. Conceptual arguments used by the French school of
      chemists to defend Antoine Lavoisier's oxygen theory against the phlogistic
      arguments (1784) of Richard Kirwan touch on the problem of criteria for
      satisfactory explanation.

PMID- 12796115
TI  - Social background of the discovery and the reception of the periodic law of the
      elements: recognizing the contributions of Dmitri Ivanovich Mendeleev and Julius
      Lothar Meyer.
AB  - The favorable and relatively rapid reception of Mendeleev's periodic table of the
      elements can be attributed, in part at least, to his social connections. These
      connections were evident in the recently organized Russian Chemical Society. In
      addition, Mendeleev enjoyed the support of the editorial board of the journal of
      the German Chemical Society.

PMID- 12796116
TI  - How G.N. Lewis reset the terms of the dialogue between chemistry and physics.
AB  - While quantum physics provided a mathematical framework for understanding the
      valency of chemical elements, to make use of these mathematical equations
      required approximations based on chemical experience. To better understand how
      this establishes limits to the presumption that chemistry can be derived from
      physics, this paper starts with the warnings in Coulson's widely read text,
      Valence, as to why there are pitfalls in the interpretation of what "valence"
      accomplishes. He directs some of these concerns back to Pauling's earlier text,
      The Nature of the Chemical Bond. Both Coulson and Pauling are aware that quantum
      theory's ability to approximate the energetic stability of chemical systems is of
      use to chemistry only if it can be correlated with the molecular structure that
      results from chemical bonding. While this may now be routinely expected, it was a
      struggle to see that this was the challenge chemistry posed to physics-and this
      achievement they both attribute to G.N. Lewis. Until the more mature forms of
      quantum mechanics arose in the 1920s, Lewis was skeptical that the dynamic models
      of the atom posed by Bohr could meet this challenge. How Lewis formulates this
      challenge initially in 1916 and then in his longer work, Valence and the
      Structure of Atoms and Molecules, will be examined.

PMID- 12796117
TI  - The superiority of "chemical thinking" for understanding free human society
      according to Hegel.
AB  - This paper examines the claim of G.W.F. Hegel (1770-1831) that "chemical
      thinking"-the method of thinking employed in chemistry-marks a significant
      advance upon (and hence is superior to) "mechanistic thinking"-the method of
      thinking characteristic of physics. This is done in the context of Mancur Olson's
      theory of collective action and public goods. The analogy between the efficiency
      of a catalyst in bringing about chemical transformation and the function of
      leaders in free human society in developing latent groups to provide public goods
      is explored.

PMID- 12796118
TI  - An organic framework for a philosophical appreciation of chemical phenomena.
AB  - The aim of this paper is to show how chemistry gives rise to philosophical
      reflection. Initially, some general remarks on philosophy and science are offered
      in the light of recent reductive controversy surrounding them both. An appeal is
      made for a broader and deeper outlook. The philosophical outlook favored is one
      of openness towards the phenomena: rather than confine them to some "-ism" or
      other. The phenomena are seen as at least potentially "bathed" in more
      encompassing levels of being. The term "ontological suppleness" is later
      introduced in this spirit, to express how something at a given level, say
      electronegativity in chemistry, has significance at far higher levels of being-in
      this case, the emergence of life, and our planet's ecology as a whole. Similar
      consideration is given to the conversion of a carcinogen (benzene) into a
      "miracle drug" (aspirin). These illustrations are intended to highlight how
      science in general, including chemistry in particular, offers seamless
      transitions to what lies beyond the scope of science. What remains for us is to
      find a language adequate to deal with such transitions.

PMID- 12796119
TI  - Chemistry beyond positivism.
AB  - Chemistry is often thought to be quite factual, and therefore might be considered
      close to the "positivist" ideal of a value-free science. A closer look, however,
      reveals that the field is coupled to the invisible realm of values, meanings, and
      purpose in various ways, and chemists interact with that realm loosely and
      unevenly. Tacit knowledge is one important locus of such interactions. We are
      concerned in this essay with two questions. What is the nature of the knowledge
      when we are in the early stages of discovery? and In what ways does the hidden
      reality we are seeking affect our search for an understanding of it? The first
      question is partly answered by Polanyi's theory of tacit knowledge, while the
      second one leads us to realize the limitations of our language when discussing
      "reality"-or certain chemical experimental results. A strictly positivist
      approach is of little use, but so is the opposite, the complete disregard of
      facts. The contrast between positivism and non-formulable aspects of scientific
      reasoning amounts to a paradox that needs to be analyzed and can lead to a
      "connected" chemistry. This in turn resembles networks described by Schweber and
      is more concerned than the chemistry "as it is" with aspects such as the image of
      chemistry, the challenges chemists face as citizens, and chemistry in liberal
      education.

PMID- 12796121
TI  - The philosophy of Kitaro Nishida and current concepts of the origin of life.
AB  - The philosophy of Kitaro Nishida is a basic metaphysics that intends to have a
      perspective beyond both Eastern and Western traditions. Nishida holds that the
      fundamental reality of the world appears from "the place of the absolute
      nothingness." Nishida's thought can be seen to have striking relationships to
      certain aspects of contemporary science and philosophy.

PMID- 12796120
TI  - Chemical self-organization, complexification, and process metaphysics.
AB  - Recognizing the self-activity of matter through complexification can lead to
      seeing evolution as a process of union. This process approach emphasizes a
      metaphysics of becoming rather than of being. Advances in the science of
      thermodynamics lead to understanding chemical self-organization as a stage in
      this process of complexification.

PMID- 12796123
TI  - The National Science Foundation and the philosophy of chemistry.
AB  - Since its founding in 1950, the National Science Foundation has provided support
      for a variety of studies in history, philosophy, and social studies of science.
      The fact that a relatively small number of projects dealing with the philosophy
      of chemistry have received NSF support is due to the small number of such
      proposals that have been submitted. The NSF Science and Technology Studies
      Program (STS) welcomes proposals dealing with philosophy of chemistry.

PMID- 12796122
TI  - Constructivism, relativism, and chemical education.
AB  - Whereas most scientists are highly critical of constructivism and relativism in
      the context of scientific knowledge acquisition, the dominant school of chemical
      education researchers appears to support a variety of such positions. By
      reference to the views of Herron, Spencer, and Bodner, I claim that these authors
      are philosophically confused, and that they are presenting a damaging and anti
      scientific message to other unsuspecting educators. Part of the problem, as I
      argue, is a failure to distinguish between pedagogical constructivism regarding
      students' understanding of science, and constructivism about the way that
      scientific knowledge is acquired by expert scientists.

PMID- 12796124
TI  - Hearts from rodents exposed to intermittent hypoxia or erythropoietin are
      protected against ischemia-reperfusion injury.
AB  - BACKGROUND: Preconditioning phenomena provide evidence for adaptive responses to
      ischemia that have important implications for treatment/prevention of myocardial
      infarction. Hypoxia-inducible factor 1 (HIF-1) mediates adaptive transcriptional
      responses to hypoxia/ischemia. METHODS AND RESULTS: Exposure of wild-type mice to
      intermittent hypoxia resulted in protection of isolated hearts against ischemia
      reperfusion injury 24 hours later. Cardiac protection induced by intermittent
      hypoxia was lost in Hif1a+/- mice heterozygous for a knockout allele at the locus
      encoding HIF-1alpha. Erythropoietin (EPO) mRNA expression was induced in kidneys
      of wild-type mice subjected to intermittent hypoxia, resulting in increased
      plasma EPO levels. EPO mRNA expression was not induced in Hif1a+/- mice. EPO
      administration to rats increased functional recovery and decreased apoptosis in
      isolated hearts subjected to ischemia-reperfusion 24 hours later. CONCLUSIONS:
      Hearts isolated from rodents subjected to intermittent hypoxia or EPO
      administration are protected against postischemic injury. Cardiac protection
      induced by intermittent hypoxia is critically dependent on Hif1a gene dosage. Our
      data suggest that additional studies to evaluate therapeutic applications of EPO
      administration are warranted.

PMID- 12796125
TI  - Antibody response to chlamydial heat shock protein 60 is strongly associated with
      acute coronary syndromes.
AB  - BACKGROUND: Heat shock proteins (HSPs) are a family of proteins with immunogenic
      and proinflammatory properties. Human and Chlamydia pneumoniae (Cp) HSP60 were
      found in patients with stable coronary disease. METHODS AND RESULTS: We measured
      the levels of anti-Cp-HSP60 and anti-Cp immunoglobulin G (IgG) in 179 patients
      with unstable angina, 40 with acute myocardial infarction, and 40 with stable
      angina (SA), as well as 100 control subjects. Forty-one patients with acute
      coronary syndromes (ACS) were also studied at follow-up. We also measured plasma
      levels of high-sensitivity C-reactive protein (hs-CRP) and troponin T (TnT).
      Seropositivity to Cp-HSP60 was found in 99% of ACS patients but in only 20% of SA
      patients and none of the control subjects. Seropositivity to Cp was detected in
      67% of ACS patients, 60% of SA patients, and 30% of the control subjects. No
      differences in Cp-HSP60 IgG and in Cp IgG were observed between patients with
      myocardial infarction and patients with unstable angina. No correlation was found
      between Cp-HSP60 IgG, TnT, and hs-CRP or between IgG against Cp and hs-CRP. In
      ACS patients at follow-up, Cp-HSP60 IgG decreased from 0.88+/-0.25 to 0.45+/-0.14
      arbitrary units (P<0.0001), becoming negative in 12 patients. CONCLUSIONS:
      Seropositivity for Cp-HSP60 appears to be a very sensitive and specific marker of
      ACS, unrelated to Cp IgG antibody titers or hs-CRP and TnT levels. Its causal
      involvement in instability and its diagnostic role in ACS deserve further study.

PMID- 12796126
TI  - Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a
      chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with
      moderate-to-severe heart failure: results of the anti-TNF Therapy Against
      Congestive Heart Failure (ATTACH) trial.
AB  - BACKGROUND: Preclinical and preliminary clinical data have suggested that tumor
      necrosis factor-alpha (TNFalpha) may play a role in the evolution and progression
      of heart failure and that inhibition of TNFalpha may favorably modify the course
      of the disease. We evaluated the efficacy and safety of infliximab, a chimeric
      monoclonal antibody to TNFalpha, in patients with moderate-to-severe heart
      failure. METHODS AND RESULTS: One hundred fifty patients with stable New York
      Heart Association class III or IV heart failure and left ventricular ejection
      fraction <or=35% were randomly assigned to receive placebo (n=49), infliximab 5
      mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after
      randomization and were followed-up prospectively for 28 weeks. Neither dose of
      infliximab improved clinical status at 14 weeks, the primary endpoint of the
      study, despite suppression of inflammatory markers (C-reactive protein and
      interleukin-6) and a modest increase in ejection fraction in the patients
      receiving 5 mg/kg (P=0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients
      were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg
      infliximab groups, respectively. The combined risk of death from any cause or
      hospitalization for heart failure through 28 weeks was increased in the patients
      randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval
      1.01 to 7.97; nominal P=0.043). CONCLUSIONS: Short-term TNFalpha antagonism with
      infliximab did not improve and high doses (10 mg/kg) adversely affected the
      clinical condition of patients with moderate-to-severe chronic heart failure.

PMID- 12796127
TI  - Prognostic value of plasma von Willebrand factor and soluble P-selectin as
      indices of endothelial damage and platelet activation in 994 patients with
      nonvalvular atrial fibrillation.
AB  - BACKGROUND: Abnormal plasma markers of a prothrombotic state have been described
      in atrial fibrillation (AF), but no such marker has yet been shown to reliably
      predict future stroke or cardiovascular outcome in AF. We hypothesized that
      raised plasma levels of von Willebrand factor (vWf, an index of endothelial
      damage/dysfunction) and/or soluble P-selectin (sP-sel, an index of platelet
      activation) might predict vascular events in AF. METHODS AND RESULTS: We measured
      vWf and sP-sel levels by ELISA in 994 participants receiving aspirin in the
      Stroke Prevention in Atrial Fibrillation III trial, at study entry or after 3
      months, and related these indices to the subsequent incidence of stroke and
      vascular events. Plasma vWf levels were a significant predictor of both stroke
      (P=0.03) and vascular events (P<0.001), with the greatest risk for those with the
      highest levels of vWf. After adjustment for other clinical predictors, the
      relationship between vWf and stroke became nonsignificant, but vWf remained an
      independent predictor of vascular events (relative risk, 1.2 [95% CI, 1.0-1.4]
      per 20 IU/dL increase in vWf; P=0.02). No significant relationships were found
      between sP-sel levels and outcome. CONCLUSIONS: Among patients with AF who
      received aspirin, raised levels of vWf (endothelial damage/dysfunction) were
      predictive of stroke and vascular events, but raised sP-sel levels (platelet
      activation) were not associated with increased cardiovascular risk. Endothelial
      damage/dysfunction (or vWf itself) may play an important role in the mechanisms
      behind stroke and cardiovascular outcome among aspirin-treated AF patients and
      might represent a target for novel therapies or an adjunctive aid to risk
      stratification in AF.

PMID- 12796128
TI  - Relationship of activated partial thromboplastin time to coronary events and
      bleeding in patients with acute coronary syndromes who receive heparin.
AB  - BACKGROUND: Antithrombotic therapy with intravenous heparin in conjunction with
      aspirin reduces negative cardiovascular (CV) outcomes in patients with acute
      coronary syndromes. The need for a therapeutic range with the activated partial
      thromboplastin time (APTT) has not been validated in patients with arterial
      thrombosis who receive heparin. Therefore, it is unclear whether there is an
      association between recurrent CV events and low APTT values and between bleeding
      and high APTT values. METHODS AND RESULTS: We examined the relationship between
      the APTT and recurrent cardiovascular events and bleeding among 5058 patients
      with an acute coronary syndrome without ST elevation who received intravenous
      heparin in the OASIS-2 trial. The increase in relative risk of recurrent CV
      events was 1.54 (95% CI 1.10 to 2.15; P=0.01) among patients with APTT values <60
      seconds compared with patients with APTT values > or =60 seconds. When patients
      had persistently subtherapeutic APTT values for more than 48 hours, the increase
      in relative risk of a recurrent CV event was 1.84 (95% CI 1.25 to 2.70). Higher
      APTT values were associated with bleeding; for every 10-second increase in the
      APTT, the probability of major bleeding was increased by 7% (95% CI 3% to 11%;
      P=0.0004). CONCLUSIONS: In patients with acute coronary syndromes without ST
      elevation who are treated with intravenous heparin, our findings justify regular
      APTT monitoring to minimize recurrent ischemic events and bleeding.

PMID- 12796129
TI  - Combined epicardial and endocardial electroanatomic mapping in a porcine model of
      healed myocardial infarction.
AB  - BACKGROUND: Substrate mapping of post-myocardial infarction ventricular
      tachycardia involves electroanatomic delineation of scarred tissue on the basis
      of electrogram characteristics during sinus rhythm. A percutaneous transthoracic
      technique was recently described that allows catheter mapping of the epicardial
      surface of the heart. This study sought to determine whether the epicardial
      extent of a myocardial infarct could be defined during sinus rhythm. METHODS AND
      RESULTS: In a porcine model of healed anterior wall myocardial infarction (n=13
      animals), detailed in vivo left ventricular endocardial and ventricular
      epicardial electroanatomic mapping was performed. Catheter access to the
      pericardial space was achieved by subxyphoid puncture under fluoroscopic
      guidance. Bipolar electrogram amplitude and duration characteristics of normal
      tissue were established on the basis of in vivo epicardial mapping data in 8
      additional normal animals. With the use of these criteria, radiofrequency lesions
      (4 to 11 per animal) were placed along the endocardial and epicardial scar
      borders as defined by the electroanatomic map. The area of epicardial scar
      defined by abnormal bipolar voltage correlated well with the dimensions measured
      on pathological examination. The size and location also correlated well with the
      scar dimensions defined by electrogram duration criteria. Late potentials were
      noted in the border zones of both surfaces of the scar. During pathological
      examination, the radiofrequency lesions were situated at the borders of the
      epicardial scar. CONCLUSIONS: A 3-dimensional construct of the infarcted
      myocardium can be rendered by combined epicardial and endocardial electroanatomic
      mapping. This experimental protocol is propaedeutic to future clinical studies
      incorporating endocardial and epicardial substrate mapping into catheter ablation
      strategies to treat post-myocardial infarction ventricular tachycardia.

PMID- 12796130
TI  - Frame count reserve.
AB  - BACKGROUND: The Doppler wire-derived (relative) coronary flow velocity reserve
      (CVR) that is used to evaluate functional significance of a coronary stenosis is
      a method performed only by interventional cardiologists. An angiographic method
      would be useful in the diagnostic catheterization laboratory. For this purpose,
      we investigated the relation between TIMI frame count reserve (FCR) and CVR.
      METHODS AND RESULTS: In 38 patients, (relative) FCR of left anterior descending
      (LAD) and left circumflex coronary artery (LCx) was calculated by using manual,
      synchronized contrast agent injections and compared with (relative) CVR. In
      addition, vessel length was measured with an intracoronary guidewire and frame
      count flow velocity was calculated and compared with average peak velocity. There
      was a strong correlation between FCR and CVR (r=0.62, P<0.001) and between
      relative FCR and relative CVR (r=0.84, P<0.001). The LAD was significantly longer
      than the LCx (mean, 14.3+/-1.6 cm versus 11.4+/-1.8 cm, P<0.001), and, therefore,
      TIMI frame count of LAD was significantly higher than of LCx (mean basal 32.5+/
      15.1 versus 23.6+/-9.1 and hyperemic 12.1+/-6.6 versus 8.7+/-3.2, both P<0.02).
      However, all flow velocity measurements and estimations of volume flow were not
      different for LAD compared with LCx. There were also no differences between mean
      FCR and CVR of LAD or LCx, of both vessels compared with each other and between
      mean relative FCR and relative CVR. CONCLUSIONS: The (relative) frame count
      reserve can be used to estimate (relative) coronary flow velocity reserve.

PMID- 12796131
TI  - Detection of TIMI-3 flow before mechanical reperfusion with ultrasonic tissue
      characterization in patients with anterior wall acute myocardial infarction.
AB  - BACKGROUND: Spontaneous coronary reperfusion with TIMI-3 flow is associated with
      favorable clinical outcomes in patients with acute myocardial infarction (AMI).
      We investigated the ability of analyzing cardiac cycle-dependent variation of
      myocardial integrated backscatter (IBS) for predicting spontaneous reperfusion in
      anterior AMI. METHODS AND RESULTS: We recorded IBS images on admission in 104
      patients with first anterior wall AMI and subsequently performed coronary
      angiography and coronary intervention. We measured the cyclic variation of IBS
      within the infarct zone and expressed its magnitude as phase-corrected magnitude
      (PCM) by giving positive and negative values when it showed synchronous and
      asynchronous contraction, respectively. Twenty-three patients showing TIMI-3 flow
      at the initial coronary angiography had smaller peak creatine kinase value than
      57 patients with initial TIMI-0/1 flow (864+/-961 versus 2358+/-1757 IU/L;
      P=0.0002) and better percent wall thickening within risk area (36.1+/-15.1%) than
      those with TIMI-2 (16.7+/-12.8%, P<0.0001) or TIMI-0/1 (5.1+/-11.6, P<0.0001).
      The patients with initial TIMI-3 had higher PCM (2.7+/-1.3 dB) than those with
      TIMI-2 (-0.3+/-2.2 dB, P<0.0001) or those with TIMI-0/1 (-1.1+/-2.4 dB,
      P<0.0001). Using PCM=1.0 dB as the cutoff point, PCM detected TIMI-3 flow with
      95.7% sensitivity and 90.1% specificity. Multivariable logistic regression
      analysis revealed that only PCM is an independent predictor for spontaneous
      reperfusion among the hemodynamic, echocardiographic, and electrocardiographic
      variables. CONCLUSIONS: Analysis of myocardial IBS could detect spontaneous
      reperfusion noninvasively in the emergent stage of anterior AMI.

PMID- 12796132
TI  - Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced
      pulmonary hypertension.
AB  - BACKGROUND: Phosphodiesterase type 5 (PDE5) is a novel therapeutic target for the
      treatment of pulmonary hypertension. This study examined the distribution of PDE5
      in normal and hypoxic lung and the effect of chronic PDE5 inhibition with
      sildenafil, initiated before and during exposure to hypoxia, on pulmonary artery
      pressure (PAP) and structure. METHODS AND RESULTS: Sprague-Dawley rats were
      exposed to hypoxia (10% O2) for up to 42 days. PAP, measured continuously by
      telemetry, increased gradually by 20 to 40 mm Hg, reaching a plateau between 10
      and 14 days, and declined to normal levels on return to normoxia. PDE5
      immunoreactivity was localized to smooth muscle cells in the medial layer of
      pulmonary arteries and veins in the normal lung and in distal muscularized
      arteries (<25 microm diameter) after hypoxia-induced pulmonary hypertension.
      Sildenafil (25 or 75 mg x kg(-1) x d(-1)) given before hypoxia produced marked
      dose-dependent inhibition in the rise of PAP (60% to 90% reduction; P<0.0001) and
      vascular muscularization (28.4+/-5.0% reduction; P<0.001). When begun after 14
      days of hypoxia, sildenafil significantly reduced PAP (30% reduction; P<0.0001)
      and partially reversed pulmonary artery muscularization (39.9+/-4.9% reduction;
      P<0.001). CONCLUSIONS: PDE5 is found throughout the muscularized pulmonary
      vascular tree, including in newly muscularized distal pulmonary arteries exposed
      to hypoxia. PDE5 inhibition attenuates the rise in PAP and vascular remodeling
      when given before chronic exposure to hypoxia and when administered as a
      treatment during ongoing hypoxia-induced pulmonary hypertension.

PMID- 12796133
TI  - Characterization of complicated carotid plaque with magnetic resonance direct
      thrombus imaging in patients with cerebral ischemia.
AB  - BACKGROUND: Thromboembolic disease secondary to complicated carotid
      atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management
      relies on the detection of significant (>70%) carotid stenosis. A large
      proportion of patients suffer irreversible cerebral ischemia as a result of
      lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic
      high-risk plaque would therefore be beneficial. High-risk plaque is defined
      histologically if it contains hemorrhage/thrombus. Magnetic resonance direct
      thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque
      hemorrhage. We assessed this as a marker of complicated plaque and compared its
      accuracy with histological examination of surgical endarterectomy specimens.
      METHODS AND RESULTS: Sixty-three patients underwent successful MRDTI and
      endarterectomy with histological examination. Of these, 44 were histologically
      defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and
      7 false-negative results, giving a sensitivity and specificity of 84%, negative
      predictive value of 70%, and positive predictive value of 93%. The interobserver
      (kappa=0.75) and intraobserver (kappa=0.9) agreement for reading MRDTI scans was
      good. CONCLUSIONS: MRDTI of the carotid vessels in patients with cerebral
      ischemia is an accurate means of identifying histologically confirmed complicated
      plaque. The high contrast generated by short T1 species within the plaque allows
      for ease of interpretation, making this technique highly applicable in the
      research and clinical setting for the investigation of carotid atherosclerotic
      disease.

PMID- 12796134
TI  - Functional changes in coronary microcirculation after valve replacement in
      patients with aortic stenosis.
AB  - BACKGROUND: Increased extravascular compression and reduced diastolic perfusion
      time (DPT), rather than vascular remodeling, influence coronary microcirculatory
      dysfunction in aortic stenosis (AS). However, alterations after aortic valve
      replacement (AVR) remain unclear. The aim of the present study was to quantify
      changes in transmural perfusion and coronary vasodilator reserve (CVR), a measure
      of microcirculatory function, after AVR and determine the relative contribution
      of left ventricular mass (LVM) regression, change in aortic valve area (AVA), and
      DPT. METHODS AND RESULTS: Twenty-two patients with AS were studied before and 1
      year after AVR using echocardiography to measure AVA, cardiovascular magnetic
      resonance to assess LVM, and positron emission tomography to quantify resting and
      hyperemic myocardial blood flow (MBF) and CVR. Regression of LVM occurred in all
      patients (from 129+/-30 to 94+/-24 g/m2; P<0.0001), and there was a significant
      reduction in resting MBF and increase in CVR corrected for rate-pressure product
      after AVR, although these changes displayed marked heterogeneity. Regression of
      LVM was linearly related to change in resting total LV blood flow but not CVR.
      Increase in hyperemic MBF and CVR transmurally was directly related to the
      increase in AVA after AVR. A significant relationship existed between the change
      in hyperemic DPT (1.0+/-4.7 s/min [range, 6.8 to 9.6]) and change in transmural
      CVR (y=0.08x+0.18; r=0.44; P=0.04). CONCLUSIONS: Changes in coronary
      microcirculatory function in patients with AS after AVR are not directly
      dependent on regression of LVM. Reduced extravascular compression and increased
      DPT are proposed as the main mechanisms for improvement in MBF and CVR after AVR.

PMID- 12796135
TI  - Increased levels of C-reactive protein after oral hormone replacement therapy may
      not be related to an increased inflammatory response.
AB  - BACKGROUND: It has been suggested that hormone replacement therapy (HRT) in
      postmenopausal women is associated with an increased inflammatory response that
      may trigger acute cardiovascular events. This suggestion is mainly based on the
      finding of elevated C-reactive protein (CRP) levels after HRT. The aim of the
      present study was to evaluate a broad spectrum of vascular inflammation markers
      in 389 postmenopausal women with increased cardiovascular risk at baseline and
      after either 6 months of HRT (126 women) or no HRT (263 women). METHODS AND
      RESULTS: Compared with baseline, CRP levels significantly increased after HRT
      (0.9+/-0.2 versus 1.6+/-0.4 mg/L, P<0.01); on the contrary, soluble intracellular
      adhesion molecule-1 decreased from 208+/-57 to 168+/-37 ng/mL (P<0.01) after HRT.
      Similarly, vascular cell adhesion molecule-1 decreased from 298+/-73 to 258+/-47
      ng/mL (P<0.01), plasma E-selectin levels were reduced from 17.8+/-5.6 to 14.8+/
      3.9 ng/mL (P<0.01), interleukin-6 levels decreased from 1.51+/-0.22 to 1.29+/
      0.28 pg/mL, and s-thrombomodulin plasma levels decreased from 4.8+/-0.7 to 4.3+/
      0.9 ng/mL (P<0.01). No significant changes in either CRP or vascular inflammatory
      marker were detected in women not taking HRT. CONCLUSIONS: The discrepancy
      between increased plasma levels of CRP and reduced plasma levels of all other
      markers of inflammation suggests that the increased CRP levels after oral HRT may
      be related to metabolic hepatic activation and not to an acute-phase response.
      HRT seems to be associated with an overall decrease in vascular inflammation.

PMID- 12796136
TI  - Prevalence of complicated carotid atheroma as detected by magnetic resonance
      direct thrombus imaging in patients with suspected carotid artery stenosis and
      previous acute cerebral ischemia.
AB  - BACKGROUND: It is recognized that complicated plaque largely accounts for the
      morbidity and mortality from atherosclerosis. Ideally, investigation of
      symptomatic and asymptomatic patients would identify atheromatous plaques
      independently of stenosis. We have previously shown that a magnetic resonance
      direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as
      high signal within the carotid arterial wall. We used this technique to examine
      the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries
      of recently symptomatic patients with suspected carotid artery stenosis and to
      compare this with their contralateral arteries and with those of healthy age- and
      sex-matched controls. METHODS AND RESULTS: The carotid arteries of 120 patients
      with suspected severe carotid artery stenosis and previous acute cerebral
      ischemia were imaged using MRDTI, as were 28 control arteries. High signal was
      not seen in any control artery. However, there was a 60% prevalence of high
      signal, suggestive of complicated plaque in the patients' ipsilateral arteries.
      The prevalence of high signal was significantly greater in the patients'
      ipsilateral vessels compared with the contralateral, asymptomatic side (60%
      versus 36%, chi2 P<0.001), particularly for vessels of only moderate stenosis.
      CONCLUSIONS: MRDTI high signal suggestive of complicated plaque is prevalent in
      the ipsilateral carotid arteries of patients with carotid stenosis and recent
      cerebral ischemic events. MRDTI has a potential role in identifying "at risk"
      plaque, studying atherogenesis and the effects of plaque-modifying strategies.

PMID- 12796137
TI  - Intracoronary beta-irradiation with a rhenium-188-filled balloon catheter: a
      randomized trial in patients with de novo and restenotic lesions.
AB  - BACKGROUND: Restenosis requiring reintervention is the main limitation of
      coronary angioplasty. Intracoronary irradiation reduces neointimal proliferation.
      We studied the efficacy of a self-centering liquid rhenium-188-filled balloon
      catheter for coronary beta-brachytherapy. METHODS AND RESULTS: After successful
      coronary angioplasty with or without stenting, 225 patients (71% de novo lesions)
      were randomly assigned to receive 22.5 Gy intravascular beta-irradiation in 0.5
      mm tissue depth (n=113) or to receive no additional intervention (n=112).
      Clinical and procedural data did not differ between the groups except a higher
      rate of stenting in the control group (63%) compared with the rhenium-188 group
      (45%, P<0.02). After 6 months of follow-up, late loss was significantly lower in
      the irradiated group compared with the control group, both of the target lesion
      (0.11+/-0.54 versus 0.69+/-0.81 mm, P<0.0001) and of the total segment (0.22+/
      0.67 versus 0.70+/-0.82 mm, P<0.0001). This was also evident in the subgroup of
      patients with de novo lesions and independent from stenting. Binary restenosis
      rates were significantly lower at the target lesion (6.3% versus 27.5%, P<0.0001)
      and of the total segment (12.6% versus 28.6%, P<0.007) after rhenium-188
      brachytherapy compared with the control group. Target vessel revascularization
      rate was significantly lower in the rhenium-188 (6.3%) compared with the control
      group (19.8%, P=0.006). CONCLUSIONS: Intracoronary beta-brachytherapy with a
      rhenium-188 liquid-filled balloon is safe and efficiently reduces restenosis and
      revascularization rates after coronary angioplasty.

PMID- 12796138
TI  - Nitric oxide-induced decrease in calcium sensitivity of resistance arteries is
      attributable to activation of the myosin light chain phosphatase and antagonized
      by the RhoA/Rho kinase pathway.
AB  - BACKGROUND: NO-induced dilations in resistance arteries (RAs) are not associated
      with decreases in vascular smooth muscle cell Ca2+. We tested whether a cGMP
      dependent activation of the smooth muscle myosin light chain phosphatase (MLCP)
      resulting in a Ca2+ desensitization of the contractile apparatus was the
      underlying mechanism and whether it could be antagonized by the RhoA pathway.
      METHODS AND RESULTS: The Ca2+ sensitivity of RA was assessed as the relation
      between changes in diameter and [Ca2+]i in depolarized RA (120 mol/L K+) exposed
      to stepwise increases in Ca2+ex (0 to 3 mmol/L). Effects of 10 micromol/L sodium
      nitroprusside (SNP) on Ca2+ sensitivity were determined before and after
      application of the soluble guanylate cyclase inhibitor ODQ (1 micromol/L) and the
      MLCP inhibitor calyculin A (120 nmol/L) and in presence of the RhoA-activating
      phospholipid sphingosine-1-phosphate (S1P, 12 nmol/L). SNP-induced dilations were
      also studied in controls and in RAs pretreated with the Rho kinase inhibitor
      Y27632 or transfected with a dominant-negative RhoA mutant (N19RhoA).
      Constrictions elicited by increasing Ca2+ex were significantly attenuated by SNP,
      which, however, left associated increases in [Ca2+]i unaffected. This NO-induced
      attenuation was blocked by ODQ, calyculin A, and S1P. The S1P-induced
      translocation of RhoA indicating activation of the GTPase was not reversed by
      SNP. Inhibition of RhoA/Rho kinase by N19RhoA or Y27632 significantly augmented
      SNP-induced dilations. CONCLUSIONS: NO dilates RA by activating the MLCP in a
      cGMP-dependent manner, thereby reducing the apparent Ca2+ sensitivity of the
      contractile apparatus. MLCP inactivation via the RhoA/Rho kinase pathway
      antagonizes this Ca2+-desensitizing effect that, in turn, can be restored using
      RhoA/Rho kinase inhibitors.

PMID- 12796139
TI  - Selective impairment in sympathetic vasomotor control with norepinephrine
      transporter inhibition.
AB  - BACKGROUND: Norepinephrine transporter (NET) inhibition increases the
      responsiveness to vasoactive medications and attenuates the response to
      sympathetic stimuli. The phenomenon may be a result of impaired regulation of
      sympathetic vasomotor tone. METHODS AND RESULTS: We studied the effects of the
      selective NET blocker reboxetine and placebo on baroreflex control of heart rate
      (HR) and sympathetic traffic in a randomized, double-blind, crossover manner in
      healthy subjects. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1
      hour before testing. ECGs were measured for HR, brachial and finger blood
      pressure (BP), and muscle sympathetic nerve activity (MSNA). Sympathetic and
      parasympathetic baroreflex slopes were determined by use of incremental
      phenylephrine and nitroprusside infusions. The dose to reach BP changes of 12.5
      mm Hg was significantly lower during NET inhibition (0.25 versus 0.64 microg x
      kg(-1) x min(-1) phenylephrine and 0.40 versus 1.10 microg x kg(-1) x min(-1)
      nitroprusside, P<0.01). Baroreflex control of HR was similar (16 ms/mm Hg with
      placebo versus 14 ms/mm Hg with reboxetine) but reset to higher BP values. MSNA
      and sympathetically mediated low-frequency BP oscillations were profoundly
      reduced at baseline and failed to increase sufficiently during nitroprusside
      infusion. Reboxetine attenuated BP and MSNA responses to cold pressor testing.
      CONCLUSIONS: NET inhibition profoundly and selectively reduces baroreflex control
      of sympathetic vasomotor tone and attenuates the responsiveness to sympathetic
      stimuli. The reduction in baroreflex buffering increases the sensitivity to
      vasoactive medications. Therefore, our findings represent a novel mechanism for
      drug interactions.

PMID- 12796140
TI  - Clopidogrel for coronary stenting: response variability, drug resistance, and the
      effect of pretreatment platelet reactivity.
AB  - BACKGROUND: Clopidogrel is administered to prevent stent thrombosis; however, the
      uniformity of platelet inhibition after treatment and the influence of
      pretreatment reactivity on drug response have not been described. METHODS AND
      RESULTS: Platelet aggregation (5 and 20 micromol/L ADP), the activation of
      glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were
      measured in patients undergoing elective coronary stenting (n=96) at baseline and
      at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received
      aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization
      laboratory and followed by 75 mg daily. There was marked interindividual
      variability in drug response as measured by all markers that showed a normal
      distribution. Resistance, defined as baseline aggregation (%) minus posttreatment
      aggregation (%) < or =10% by 5 micromol/L ADP, was present in 31% and 15% of
      patients at 5 and 30 days, respectively. Patients with the highest pretreatment
      platelet reactivity remained the most reactive at 24 hours after treatment
      (P<0.0001). CONCLUSIONS: Interindividual variability in the platelet inhibitory
      response from clopidogrel occurs in patients undergoing elective coronary
      stenting. Patients with high pretreatment reactivity are least protected.
      Alternative pharmacological strategies and the association of adverse ischemic
      events should be investigated in these patients.

PMID- 12796141
TI  - Prognostic impact of hemodynamic response to adenosine in patients older than age
      55 years undergoing vasodilator stress myocardial perfusion study.
AB  - BACKGROUND: The prognostic importance of various hemodynamic responses to
      adenosine infusion in patients undergoing adenosine stress myocardial perfusion
      stress (MPS) has not been defined. METHODS AND RESULTS: We identified 3444 unique
      patients (53.5% women, mean age 74.0+/-8.4 years) who underwent adenosine (with
      no additional exercise) stress myocardial perfusion single photon emission
      computed tomography (MPS) and were followed up for 2.0+/-0.8 years. Multivariable
      Cox proportional hazards analysis was used to assess the prognostic value of
      hemodynamic variables in predicting cardiac death (CD). Two hundred twenty-four
      CDs (6.5%) occurred during follow-up. By multivariable analysis, higher rest
      heart rate (HR) and to a lesser extent lower peak HR were markers of CD. When
      added to the multivariable model in place of peak and rest HR, the peak/rest HR
      ratio was an independent predictor of CD. Peak/rest HR ratio additionally risk
      stratified patients within each MPS category. A significant interaction was found
      between gender and peak systolic blood pressure (SBP), in which there was an
      increased risk associated with a low peak SBP (<90 mm Hg at end of adenosine
      infusion) in men but not in women. CONCLUSIONS: Patients undergoing adenosine
      stress MPS with high rest HR and low peak/rest HR ratio have increased risk of
      CD, as do male patients with a low peak SBP. Assessment of the hemodynamic
      response to adenosine adds incremental prognostic value to MPS results and
      enhances identification of patients at risk for CD.

PMID- 12796142
TI  - Expression of human hepatic lipase in the rabbit model preferentially enhances
      the clearance of triglyceride-enriched versus native high-density lipoprotein
      apolipoprotein A-I.
AB  - BACKGROUND: We have shown previously that triglyceride (TG) enrichment of HDL, as
      occurs in hypertriglyceridemic states, contributes to HDL lowering in humans by
      enhancing the clearance of HDL apolipoprotein (apo) A-I from the circulation. In
      the New Zealand White rabbit, an animal naturally deficient in hepatic lipase
      (HL), we demonstrated that TG enrichment of HDL per se is not sufficient to
      enhance HDL clearance in the absence of ex vivo lipolysis by HL. Here, we
      examined in the rabbit the interaction between in vivo HL lipolytic action and
      HDL TG enrichment on the subsequent metabolic clearance of HDL apoA-I. METHODS
      AND RESULTS: The clearance of HDL, TG-enriched with human VLDL (12% mass TG), was
      compared with a simultaneously injected native rabbit HDL tracer (8% TG) 5 to 7
      days after injection of recombinant (r) adenovirus expressing either the human HL
      or lacZ transgene (n=6 animals each). In rHL-Adv rabbits, HL activity levels were
      2- to 7-fold higher (versus rlacZ-Adv controls; P<0.01), and there were
      significant (P<0.05) reductions in HDL TG (-18%), cholesterol (-21%), cholesteryl
      ester (-24%), and phospholipid (-14%). Moreover, the clearance of TG-enriched
      versus native HDL was significantly greater (by 50%; 0.122+/-0.022 versus 0.081+/
      0.015 pools/h; P<0.01) in rHL-Adv rabbits but not in controls. CONCLUSIONS: These
      studies have shown that TG enrichment of HDL in the presence but not in the
      absence of in vivo expression of moderate levels of lipolytically active HL
      results in enhanced HDL clearance, demonstrating the important interaction
      between TG enrichment and HL action in the pathogenesis of HDL lowering in
      hypertriglyceridemic states.

PMID- 12796143
TI  - Stimulation of protein kinase C inhibits bursting in disease-linked mutant human
      cardiac sodium channels.
AB  - BACKGROUND: Mutations in SCN5A, the gene coding for the human cardiac Na+ channel
      alpha-subunit, are associated with variant 3 of the long-QT syndrome (LQT-3).
      Several LQT-3 mutations promote a mode of Na+ channel gating in which a fraction
      of channels fail to inactivate, contributing sustained Na+ channel current
      (Isus), which can delay repolarization and prolong the QT interval. Here, we
      investigate the possibility that stimulation of protein kinase C (PKC) may
      modulate Isus, which is prominent in disease-related Na+ channel mutations.
      METHODS AND RESULTS: We measured the effects of PKC stimulation on Na+ currents
      in human embryonic kidney (HEK 293) cells expressing 3 previously reported
      disease-associated Na+ channel mutations (Y1795C, Y1795H, and DeltaKPQ). We find
      that the PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) significantly reduced
      Isus in the mutant but not wild-type channels. The effect of OAG on Isus was
      reduced by the PKC inhibitor staurosporine (2.5 micromol/L), ablated by the
      mutation S1503A, and mimicked by the mutation S1503D. Isus recorded in myocytes
      isolated from mice expressing DeltaKPQ channels was similarly inhibited by OAG
      exposure or stimulation of alpha1-adrenergic receptors by phenylephrine. The
      actions of phenylephrine on Isus were blocked by the PKC inhibitor chelerythrine.
      CONCLUSIONS: We conclude that stimulation of PKC inhibits channel bursting in
      disease-linked mutations via phosphorylation-induced alteration of the charge at
      residue 1503 of the Na+ channel alpha-subunit. Sympathetic nerve activity may
      contribute directly to suppression of mutant channel bursting via alpha
      adrenergic receptor-mediated stimulation of PKC.

PMID- 12796144
TI  - Anterior mitral leaflet mobility is limited by the basal stay chords.
AB  - BACKGROUND: We hypothesize that 2 tendon-like anterior basal stay chords, which
      remain taut during the entire cardiac cycle, limit the motion of the anterior
      mitral leaflet. METHODS AND RESULTS: Sonomicrometric crystals were implanted in 6
      sheep at the insertion of stay chords at anterior mitral leaflet (S1 and S2),
      papillary muscle tips, fibrous trigones, mitral annulus, and the tip of the
      anterior leaflet (AL). Distances between crystals were recorded before and after
      section of stay chords. During the cardiac cycle, the angle alpha between mitral
      annulus and AL changed by +54.2+/-12.4 degrees; the angles between mitral annulus
      and S1 (beta1) changed by +25.7+/-14.6 degrees, and between mitral annulus and S2
      (beta2) by +20.4+/-7.8 degrees. During diastole, AL twice crossed the virtual
      plane formed by the stay chords: during E-wave by a maximum of 6.5 mm (mean,
      2.5+/-2.2 mm) and during A-wave by a maximum of 3.2 mm (mean, 1.7+/-0.9 mm).
      After section of both stay chords, total anterior mitral leaflet motion increased
      as follows: AL, +6.9+/-3.4 degrees; S1, +13.1+/-4.4 degrees; and S2, +30.9+/-11.7
      degrees (P<0.05). CONCLUSIONS: Although the lateral movement of anterior mitral
      leaflet is limited by stay chords, the midportion moves unimpaired toward the
      septum, like a sail, between the 2 stay chords during diastole. A diastolic left
      ventricular-inflow and systolic left ventricular-outflow funnel mechanism is
      created. Stay chord section increased lateral anterior mitral leaflet movement.

PMID- 12796145
TI  - Viewpoints to liberation from mechanical ventilation.

PMID- 12796146
TI  - Lung retransplantation: all for one or one for all?

PMID- 12796147
TI  - Cardiac biomarkers in pulmonary embolism.

PMID- 12796148
TI  - Practice guidelines for noninvasive positive-pressure ventilation: help or
      hindrance?

PMID- 12796149
TI  - Induced sputum analysis for T helper type 2 cell regulation: closing the loop.

PMID- 12796150
TI  - To screen or not to screen: a volatile issue in lung cancer.

PMID- 12796151
TI  - A scientific koan: what is the cause of cystic fibrosis?

PMID- 12796152
TI  - Exercise training improves exertional dyspnea in patients with COPD: evidence of
      the role of mechanical factors.
AB  - BACKGROUND: To our knowledge, no data have been reported on the effects of
      exercise training (EXT) on central respiratory motor output or neuromuscular
      coupling (NMC) of the ventilatory pump, and their potential association with
      exertional dyspnea. Accurate assessment of these important clinical outcomes is
      integral to effective management of breathlessness of patients with COPD.
      MATERIAL AND METHODS: Twenty consecutive patients with stable moderate-to-severe
      COPD were tested at 6-week intervals at baseline, after a nonintervention control
      period (pre-EXT), and after EXT. Patients entered an outpatient pulmonary
      rehabilitation program involving regular exercise on a bicycle. Incremental
      symptom-limited exercise testing (1-min increments of 10 W) was performed on an
      electronically braked cycle ergometer. Oxygen uptake (O(2)), carbon dioxide
      output (CO(2)), minute ventilation (E), time, and volume components of the
      respiratory cycle and, in six patients, esophageal pressure swings (Pessw), both
      as actual values and as percentage of maximal (most negative in sign) esophageal
      pressure during sniff maneuver (Pessn), were measured continuously over the runs.
      Exertional dyspnea and leg effort were evaluated by administering a Borg scale.
      RESULTS: Measurements at baseline and pre-EXT were similar. Significant increase
      in exercise capacity was found in response to EXT: (1) peak work rate (WR), O(2),
      CO(2), E, tidal volume (VT), and heart rate increased, while peak exertional
      dyspnea and leg effort did not significantly change; (2) exertional dyspnea/O(2)
      and exertional dyspnea/CO(2) decreased while E/O(2) and E/CO(2) remained
      unchanged. The slope of both exertional dyspnea and leg effort relative to E fell
      significantly after EXT; (3) at standardized WR, E, and CO(2), exertional dyspnea
      and leg effort decreased while inspiratory capacity (IC) increased. Decrease in E
      was accomplished primarily by decrease in respiratory rate (RR) and increase in
      both inspiratory time (TI) and expiratory time; VT slightly increased, while
      inspiratory drive (VT/TI) and duty cycle (TI/total time of the respiratory cycle)
      remained unchanged. The decrease in Pessw and the increase in VT were associated
      with lower exertional dyspnea after EXT; (4) at standardized E, VT, RR, and IC,
      Pessw and Pessw(%Pessn)/VT remained unchanged while exertional dyspnea and leg
      effort decreased with EXT. CONCLUSION: In conclusion, increases in NMC, aerobic
      capacity, and tolerance to dyspnogenic stimuli and possibly breathing retraining
      are likely to contribute to the relief of both exertional dyspnea and leg effort
      after EXT.

PMID- 12796153
TI  - Pulmonary vascular responses to hypoxia and hyperoxia in healthy volunteers and
      COPD patients measured by electrical impedance tomography.
AB  - BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive imaging
      technique using impedance to visualize and measure blood volume changes. STUDY
      OBJECTIVE: To examine the validity of EIT in the measurement of hypoxic pulmonary
      vasoconstriction (HPV) and hyperoxic pulmonary vasodilation in healthy volunteers
      and COPD patients. PARTICIPANTS: Group 1 consisted of seven healthy volunteers
      (mean age, 46 years; age range, 36 to 53 years). Group 2 comprised six clinically
      stable COPD patients (mean age, 65 years; age range, 50 to 74 years).
      INTERVENTIONS: EIT measurements were performed in healthy subjects while they
      were breathing room air, 14% oxygen (ie, hypoxia), and 100% oxygen (ie,
      hyperoxia) through a mouthpiece. Maximal impedance change during systole
      (DeltaZsys) was used as a measure of pulmonary perfusion-related impedance
      changes. Stroke volume (SV) was measured by means of MRI. In the COPD group, EIT
      and SV also were determined, but only in room air and under hyperoxic conditions.
      RESULTS: The data were statistically compared to data for the room air baseline
      condition. In the volunteers, the mean (+/- SD) DeltaZsys for the group was 352
      +/- 53 arbitrary units (AU) while breathing room air, 309 +/- 75 AU in hypoxia (p
      < 0.05), and 341 +/- 69 AU in hyperoxia (not significant [NS]). The mean MRI
      measured SV was 83 +/- 21 mL while breathing room air, 90 +/- 29) mL in hypoxia
      (NS), and 94 +/- 19 mL in hyperoxia (p < 0.05). In the COPD patients, the mean
      DeltaZsys for this group was 222 +/- 84 AU while breathing room air and 255 +/-
      83 AU in hyperoxia (p < 0.05). In this group, the SV was 59 +/- 16 mL while
      breathing room air and 61 +/- 13 mL in hyperoxia (NS). Thus, the volunteer EIT
      response to hypoxia is not caused by decreased SV, because SV did not show a
      significant decrease. Similarly, in COPD patients the EIT response to hyperoxia
      is not caused by increased SV, because SV showed only a minor change. CONCLUSION:
      EIT can detect blood volume changes due to HPV noninvasively in healthy subjects
      and hyperoxic vasodilation in COPD patients.

PMID- 12796154
TI  - A comparison of the effects of salbutamol and ipratropium bromide on exercise
      endurance in patients with COPD.
AB  - STUDY OBJECTIVE: Inhaled bronchodilators are the first-line pharmacotherapy
      against COPD. The purpose of the present study was to investigate the effects of
      beta(2)-agonists and anticholinergic agents on the exercise capacity of patients
      with COPD. METHODS: A total of 67 stable patients with COPD were recruited at the
      Kyoto University Hospital. After inhaling 400 micro g salbutamol, 80 micro g
      ipratropium bromide, or an identical placebo in a randomized, double-blind,
      crossover fashion, the patients performed cycle endurance tests at a constant
      workload of 80% of the maximum work rate reached on progressive cycle ergometry,
      and the endurance time was recorded. RESULTS: Both salbutamol and ipratropium
      bromide significantly improved the endurance time by 29 s (15%; p < 0.001) and 27
      s (14%; p < 0.001), respectively, in comparison with the placebo. However, there
      was no statistically significant difference between them (p = 0.71). The dyspnea
      ratios were also similarly reduced by both bronchodilators. The difference in the
      endurance time between therapy with salbutamol and placebo was significantly, but
      moderately, related to the difference between therapy with ipratropium bromide
      and placebo. In addition, there were no relationships, or only weakly significant
      relationships, between the change in FEV(1) and the change in the endurance time,
      the highest oxygen uptake, and the highest minute ventilation for both salbutamol
      and ipratropium bromide. CONCLUSIONS: Therapy with both salbutamol and
      ipratropium bromide improved exercise capacity, as evaluated by the endurance
      time, and reduced dyspnea similarly in patients with COPD. In addition, the
      effects of the different bronchodilators on exercise capacity varied within
      individuals, and a complex mechanism may be responsible for the different effects
      of these two bronchodilators on exercise capacity vs airflow limitation. These
      results support the conclusion that both types of inhaled bronchodilators can be
      used as first-line drugs for the treatment of stable patients with COPD.

PMID- 12796155
TI  - Cardiovascular safety of salmeterol in COPD.
AB  - BACKGROUND: Patients with COPD have an increased risk of cardiovascular disease.
      Despite the clinical benefits of long-acting beta-agonist agents in the treatment
      of COPD, patients may be at an increased risk of cardiovascular toxicity,
      including tachyarrhythmia due to beta-adrenergic stimulation. OBJECTIVE: To
      evaluate the cardiovascular safety of salmeterol in COPD patients by conducting a
      pooled analysis of cardiovascular safety data. DESIGN: Randomized, double-blind,
      parallel group, multiple-dose studies, which included salmeterol, 50 micro g bid,
      and placebo arms. STUDY SELECTION: Seven of a total of 17 studies met the
      predefined inclusion requirements and were pooled. A total of 1,443 patients
      received placebo, while 1,410 patients received salmeterol, 50 micro g bid. The
      median duration of treatment was 24 weeks (range, 12 to 52 weeks). RESULTS:
      Treatment with salmeterol, 50 micro g bid, showed no increased risk of
      cardiovascular adverse events (AEs) compared with placebo (relative risk, 1.03;
      95% confidence interval, 0.8 to 1.3; p = 0.838). Both groups had a similar
      incidence of cardiovascular events (8%), including cardiovascular deaths. The
      incidence of cardiovascular AEs increased with age, concurrent cardiovascular
      conditions, and treatment with antiarrhythmic/bradycardic agents, although
      increases were comparable in both treatment groups. There were no episodes of
      sustained ventricular tachycardia, and no clinically significant differences were
      observed in 24-h heart rate, ventricular and supraventricular ectopic events,
      qualitative ECGs, QT intervals, or vital signs between the salmeterol, 50 micro g
      bid, group and the placebo group. Similar findings were observed when patients
      were stratified for age of > 65 years or the known presence of cardiovascular
      disease. CONCLUSIONS: Treatment with salmeterol, 50 micro g bid, does not
      increase the risk of cardiovascular AEs in this population of COPD patients
      compared with placebo.

PMID- 12796156
TI  - Human leukocyte antigen mismatches predispose to the severity of bronchiolitis
      obliterans syndrome after lung transplantation.
AB  - BACKGROUND: Obliterative bronchiolitis (OB) is the most important cause of long
      term morbidity and mortality in lung transplant recipients, and probably results
      from alloimmune airway injury. Bronchiolitis obliterans syndrome (BOS), defined
      as a staged decline in pulmonary function, is the clinical correlate of OB.
      OBJECTIVE: Evaluation of the risk and severity of BOS on the basis of the
      incompatibility of donor and recipient human leukocyte antigen (HLA) molecules.
      DESIGN: Retrospective cohort study. SETTING: Large university hospital.
      PARTICIPANTS: Lung transplant recipients between January 1990 and January 2000.
      MEASUREMENTS: We determined the BOS stage using internationally promulgated
      guidelines with a minor modification on all recipients at their 4-year transplant
      anniversary. Recipients whose graft function had deteriorated or who died due to
      causes other than BOS were excluded from the study. HLA loci mismatches and other
      covariables, including recipient age, donor age, cytomegalovirus (CMV) mismatch,
      cold ischemic time, use of cardiopulmonary bypass, ventilatory days, episodes of
      acute rejection and CMV pneumonitis, mean trough cyclosporin A (CsA) level,
      episodes of subtherapeutic CsA levels, and histopathology of OB and diffuse
      alveolar damage were entered into the analysis of BOS predictors. RESULTS: Sixty
      four patients met the inclusion and exclusion criteria of the study at the 4-year
      posttransplant time point. In univariate analyses, the number of combined HLA-A
      and HLA-B mismatches was strongly associated with the stage of BOS at 4 years (p
      = 0.002). This association remained significant after the inclusion of other
      potential risk factors for BOS in multiple linear regression models.
      Pretransplant and posttransplant proportional odds models confirmed that the
      increasing number of combined HLA-A and HLA-B mismatches increased the overall
      severity of BOS (adjusted odds ratio, 1.84 [p = 0.035] vs 1.69 [p = 0.067],
      respectively). A trend toward significance was seen with HLA-DR mismatching (p =
      0.17). CONCLUSIONS: The degree of HLA class I mismatching between donors and
      recipients predisposes lung transplant recipients to the development and severity
      of BOS.

PMID- 12796157
TI  - Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up
      in a series of 15 recipients.
AB  - BACKGROUND: Although lung retransplantation is the only definitive therapeutic
      option in lung recipients with bronchiolitis obliterans syndrome (BOS), its value
      remains a considerable source of controversy. We report our experience of
      retransplantation for BOS performed in our center since 1988. METHODS: Between
      1988 and 2002, 15 lung retransplantations for BOS were performed. Patient
      survival, causes of death, long-term functional status, and BOS recurrence rate
      were reviewed. RESULTS: The retransplantation procedure was single-lung
      transplantation (SLT) in all cases (ipsilateral SLT, n = 4; contralateral SLT, n
      = 9; SLT after previous double-lung transplantation, n = 2). The median time
      between primary lung transplantation and retransplantation was 31 months (range,
      12 to 39 months). The median follow-up duration of the 10 patients surviving
      beyond 6 months was 49.5 months (range, 16.5 to 105 months), and 5 patients were
      followed up for > 5 years. Actuarial survival rates at 1 year, 2 years, and 5
      years after retransplantation were 60%, 53%, and 45%, respectively. Ten patients
      died during long-term follow-up, 6 of them from infection (60%). The retained
      graft was the initial site of the fatal infection in four of these six patients
      (66%). Two other patients with a retained graft experienced disabling chronic
      purulent expectoration arising from the old graft. In the 10 patients surviving
      beyond 6 months, mean best FEV(1) was 58 +/- 13% of predicted (+/- SD), and
      actuarial freedom from BOS (stage 1, 2, or 3) at 1 year, 3 years, and 5 years was
      90%, 72%, and 66%, respectively. CONCLUSION: Lung retransplantation offered a
      viable therapeutic option for selected lung recipients with BOS. Given the
      morbidity and mortality related to the retained graft, we now favor replacement
      of the primary graft when retransplantation is considered.

PMID- 12796158
TI  - Sustained improvements in dyspnea and pulmonary function 3 to 5 years after lung
      volume reduction surgery.
AB  - OBJECTIVES: To determine long-term survival rates of patients who underwent lung
      volume reduction surgery (LVRS) for emphysema and the factors associated with
      longer survival, and to evaluate levels of perceived dyspnea and health-related
      quality of life (HRQL) after a follow-up period of 3 to 5.5 years. DESIGN:
      Retrospective observational study. SETTING: Academic medical center METHODS:
      Telephone and postal surveys were used to obtain patient dyspnea scores and HRQL
      scores. Hospital databases and state registries were searched to determine
      patient survival and pulmonary function. RESULTS: Of 54 patients undergoing LVRS,
      29 patients (18 men and 11 women) were available for follow-up, which ranged from
      36 to 66 months (mean +/- SE, 51 +/- 1.5 months). There was significant sustained
      improvement in modified Medical Research Council scores compared to pre-LVRS:
      2.19 +/- 0.19 vs 2.88 +/- 0.14 (p = 0.0000). Eleven of 22 patients demonstrated
      an increase in all three Mahler baseline dyspnea index grades of at least one
      level. Baseline body mass index (BMI) and post-LVRS length of stay (LOS) were
      significantly associated with survival: survivor vs deceased baseline BMI, 24.2
      +/- 0.6 vs 21.4 +/- 0.5 (p = 0.002), and post-LVRS LOS, 15.4 +/- 1.7 days vs 28.7
      +/- 5.3 days (p = 0.015). Compared to pre-LVRS, 20 patients with mean follow-up
      time of 45 months demonstrated significant sustained improvements in FEV(1)
      percentage of predicted (31.4 +/- 2.1% vs 39.8 +/- 3.5%, p = 0.038), total lung
      capacity percentage of predicted (136 +/- 4% vs 122 +/- 3%, p = 0.0004), and
      residual volume percentage of predicted (237 +/- 14% vs 172 +/- 11%, p = 0.0001).
      Patient HRQL measured using the Dartmouth Primary Care Co-operative Quality of
      Life questionnaire was more favorable than that reported in aged-care settings.
      Caregiver burden scale scores indicate caring for a recipient of LVRS carries
      similar burden to that for caring for individuals with other chronic illnesses.
      CONCLUSIONS: In this population, a majority of the LVRS patients survived for >/=
      3 years. Among survivors, dyspnea and lung function benefits were seen. Baseline
      BMI and postoperative LOS were significantly associated with survival.

PMID- 12796160
TI  - Volume expansion with albumin decreases mortality after coronary artery bypass
      graft surgery.
AB  - OBJECTIVES: Albumin and nonprotein colloids (starches, dextran, and others) are
      used frequently as blood volume expanders in coronary artery bypass graft (CABG)
      surgery. The objective of this study was to determine differences between
      colloids with regard to patient characteristics and mortality rates. DESIGN AND
      SETTING: Discharge data collected in the Solucient Clinical Pathways Database
      from 19,578 patients undergoing CABG surgery were analyzed. MEASUREMENTS:
      Patients receiving albumin and nonprotein colloids were compared with regard to
      baseline patient characteristics. A multiple regression model was developed to
      determine if albumin use was independently associated with mortality rates.
      RESULTS: Albumin was used in 8,084 cases (41.3%). The use of albumin and
      nonprotein colloids was not related to patient characteristics. Mortality was
      lower in the albumin group compared to the nonprotein colloid group (2.47% vs
      3.03%, p = 0.02). In the multivariable logistic regression analysis, albumin use
      was associated with 25% lower odds of mortality compared to nonprotein colloid
      use (odds ratio, 0.80; 95% confidence interval, 0.67 to 0.96). CONCLUSION:
      Colloid administration in CABG surgery was unrelated to patient characteristics.
      Albumin use appears to be associated with lower incidence of mortality after CABG
      surgery compared to nonprotein colloid use.

PMID- 12796159
TI  - Effects of lung volume reduction surgery for emphysema on oxygen cost of
      breathing.
AB  - BACKGROUND: Patients with severe pulmonary emphysema have a greatly increased
      oxygen cost of breathing (O(2) cost), and this is the cause of serious
      malnutrition, or respiratory cachexia, in such patients. STUDY OBJECTIVES: To
      clarify the effect of lung volume reduction surgery (LVRS) on respiratory
      function and the nutritional state of these patients through a reduction in the
      O(2) cost of the respiratory muscles. DESIGN: Prospective cohort study. Setting,
      patients, and interventions: Twenty-three patients who underwent LVRS in Tohoku
      University Hospital. MEASUREMENTS: Pulmonary function and O(2) cost were measured
      perioperatively by utilizing a method of continuous dead space. In addition, we
      calculated the proportion of oxygen consumption (O(2)) of respiratory muscles to
      total O(2) (%O(2)resp) from the measured energy expenditure and the predicted
      values. RESULTS: FEV(1) and arterial oxygen pressure increased after surgery
      while lung volume and dyspnea decreased (p < 0.01), and O(2) cost was also
      reduced from 0.044 to 0.026 log(mL/min)/(L/min) [p < 0.001]. Moreover, the change
      in O(2) cost had a strong negative correlation with that of FEV(1) (r = - 0.70, p
      < 0.001), and a moderate positive correlation with that of the ratio of residual
      volume to total lung capacity (r = 0.54, p < 0.01). %O(2)resp was 23.1% at rest
      and 55.5% at maximal ventilation. LVRS reduced %O(2)resp at maximal ventilation
      to 49.0% (p < 0.05), but %O(2)resp at rest did not decrease after surgery.
      CONCLUSIONS: LVRS reduces energy expenditure of respiratory muscles especially
      during exercise by decreasing small airway obstruction and hyperinflated lung
      volume. This may reverse the malnourished state in end-stage emphysema.

PMID- 12796161
TI  - Risk of recurrence in patients with surgically resected stage I non-small cell
      lung carcinoma: histopathologic and immunohistochemical analysis.
AB  - STUDY OBJECTIVE: To evaluate the prognostic value of histopathologic variables
      and molecular markers in a group of patients with stage I non-small cell lung
      cancer (NSCLC). SETTING: "Maria Ferrer" Hospital of Buenos Aires, Argentina.
      PATIENTS: Pathologic stage IA and IB patients who underwent radical surgery and
      nonneoadjuvant therapy for NSCLC between January 1985 and December 1999.
      MEASUREMENTS AND RESULTS: Fifty-three patients fulfilling the inclusion criteria
      were identified. The overall survival was 52.8%, and 28% of patients had
      recurrent disease. We found significant differences between squamous cell
      carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic
      permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p
      = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than
      adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1,
      and Bcl-2 were predictive factors for relapse. All of them were associated with
      increased relapse and a shorter time to recurrence. Multivariate analysis using
      the Cox proportional hazards regression model showed that mitosis count, Bcl-2
      expression, and grade 3 of MIB-1 emerged as independent prognostic factors of
      recurrence. CONCLUSIONS: We found that mitosis count and MIB-1 expression had
      significant value to predict recurrence, reflecting the aggressiveness of high
      rate proliferative tumors. We could also show that patients with positive Bcl-2
      tumors had a poor outcome, probably related to the uncontrolled cell growth that
      the expression of Bcl-2 promotes. Our observations are of potential interest for
      the development of rational postresection treatment strategies based on the
      estimated risk of recurrence of patients with NSCLC.

PMID- 12796162
TI  - Clinical characteristics of pneumonic-type adenocarcinoma of the lung.
AB  - PURPOSE: To analyze diagnostic approaches, survival predictors, and treatment
      efficacy in pneumonic-type adenocarcinoma (P-ADC). PATIENTS AND METHODS: Fifty
      two patients with P-ADC diagnosed between January 1986 and December 2000 were
      studied. P-ADC was defined as histologically or cytologically proven pulmonary
      adenocarcinoma with a pneumonia-like consolidation, in a patient with no prior
      diagnosis of thoracic or extrathoracic adenocarcinoma. RESULTS: Sixty percent of
      the patients were men (n = 31), and 65% (n = 34) were current or former smokers.
      Mean (+/- SD) age at diagnosis was 66 +/- 1.4 years. P-ADC was diagnosed by
      routine chest radiography in 17% of cases (n = 9). Bronchorrhea was present in
      31% of cases (n = 16), and crepitant rales in 58% (n = 30). The primary tumor
      appeared as consolidations, which could not be assessed and were thus classified
      Tx, in 83% of the patients (n = 43). Ten percent of the patients (n = 5) had a
      satellite tumor within the lobe containing the primary tumor (T4), and 63% (n =
      33) had a satellite tumor in another lobe (M1). Extrathoracic metastases were
      present in 5% of cases (n = 3). Bronchial biopsy, transbronchial biopsy,
      bronchial aspiration, and BAL were positive in 21%, 80%, 44%, and 66% of cases,
      respectively. The median survival time after diagnosis was 10.5 months (range, 1
      to 150 months). The outcome of patients treated by lobectomy or bilobectomy was
      significantly better than that of patients treated with pneumonectomy,
      chemotherapy, or best supportive care (p < 0.01). Bronchorrhea and crepitant
      rales were independent predictors of shorter survival when the treatment modality
      (surgery vs no surgery) was not entered as a risk factor. CONCLUSIONS: P-ADC is
      characterized by aerogenous propagation, as emphasized by the results of
      multivariate analysis showing that bronchorrhea and crepitant rales were the only
      two independent factors of shorter survival. Surgery remains the most effective
      treatment in P-ADC, especially when lobectomy is feasible. As CT is not sensitive
      enough to detect multifocal lesions, new tools are required to evaluate pulmonary
      involvement and thereby to refine the surgical strategy.

PMID- 12796163
TI  - Comparison of function of commercially available pleural drainage units and
      catheters.
AB  - PURPOSE: Flow rates and pressures generated by commercially available pleural
      drainage units (PDUs) and flow rates through available pleural drainage catheters
      (PDCs) are not known. This information may be important clinically depending on
      the volume of air leak associated with a bronchopleural fistula. DESIGN: Eight
      PDUs were assessed for flow rates at various suction levels and for the percent
      accuracy of suction pressures generated at various settings. Eleven commonly used
      PDCs were assessed for flow rates at various suction control levels. All devices
      were donated by their manufacturer. Flow rates and pressures were measured by a
      RT 200 Calibration Analyzer (Timeter Instrument Corporation; St. Louis, MO) at
      body temperature, ambient pressure, saturated with water vapor. Five devices of
      each type were tested. Analysis of variance was performed with p < 0.05 being
      significant. RESULTS: Multiple significant differences between PDUs were noted at
      a pressure of - 20 cm H(2)O. The Argyle Sentinel Seal (Sherwood Medical;
      Tillamore, Ireland) had significantly lower flow rates (mean +/- SD, 10.8 +/- 0.6
      L/min) compared with all other models. The Argyle Aqua-Seal (Sherwood Medical)
      had the highest PDU flow rate of devices tested (42.1 +/- 1.0 L/min). The
      accuracy of PDUs at manufacturer-suggested settings varied from a mean percentage
      error of 0.0 to 15.5% from expected pressures; significant differences were noted
      in accuracy among multiple interdevice pressure comparisons. Similarly, multiple
      significant flow rate differences between PDCs were noted at - 20 cm H(2)O.
      Lowest flow rates were noted with thoracentesis catheters (used as PDCs)
      containing side ports. Arrow drainage catheters (14F, pigtail and straight)
      [Arrow International; Reading, PA] both had significantly greater flow rates
      (both, 16.8 +/- 0.1 L/min), compared with the 14F (12.8 +/- 0.3) and 16F (14.8 +/
      0.6) Cook devices (Cook; Bloomington, IN). CONCLUSIONS: These differences in
      flow rates for PDUs and PDCs may be clinically important, particularly in
      patients with large pneumothorax-related air leaks. Observed differences in PDU
      generated pressures are likely not clinically important.

PMID- 12796164
TI  - Multilevel and continuous pleural fluid pH likelihood ratios for evaluating
      malignant pleural effusions.
AB  - STUDY OBJECTIVE: Expert consensus recommends testing pleural fluid for pH to
      assist the selection of patients with malignant pleural effusions for
      pleurodesis. Although published studies report an association between pleural
      fluid pH and patient outcomes after pleurodesis, clinicians have no definitive
      information on how to use pH to select patients for pleurodesis. Thus, we
      quantitatively assessed different methods for deriving likelihood ratios from
      pleural fluid pH and evaluated the potential role of pH in selecting patients for
      pleurodesis. DATA SOURCES: MEDLINE, systematic reviews, article reference lists,
      and contact with primary authors. STUDY SELECTION: Studies that assessed the
      impact of pleural fluid pH on survival and pleurodesis failure rates among
      patients with malignant pleural effusions. DATA EXTRACTION: Primary authors
      provided their data in electronic spreadsheets. DATA SYNTHESIS: Retrieved data
      sets included survival and pleurodesis failure rates for 417 patients and 433
      patients, respectively. Binary, multilevel, and continuous likelihood ratios were
      calculated to estimate the likelihood of death within 3 months of pleurodesis or
      pleurodesis failure rates. Values for the likelihood ratios were compared for
      each of the three strategies, and relative clinical and statistical significance
      were assessed. Pleural fluid pH had marginal performance for identifying patients
      with < 3-month anticipated survival; binary likelihood ratios provided as much
      information as the multilevel and continuous strategies. Likelihood ratios for
      identifying patients likely to fail pleurodesis were clinically useful.
      Continuous likelihood ratios provided statistically more information as compared
      with the multilevel and binary strategies. CONCLUSIONS: Pleural fluid pH has
      marginal value for estimating death within 3 months of pleurodesis, and binary
      likelihood ratios (cut point </= 7.20) perform as well as the other strategies
      assessed. Pleural fluid pH provides more useful information for estimating the
      likelihood of pleurodesis failure for which continuous likelihood ratios provide
      the most information as compared with binary or multilevel likelihood ratios.

PMID- 12796165
TI  - Rapid pleurodesis for malignant pleural effusions.
AB  - STUDY OBJECTIVE: To determine the feasibility of rapid pleurodesis in patients
      with malignant pleural effusions in order to reduce hospital length of stay in
      patients with a limited life expectancy. DESIGN: Prospective case series.
      SETTING: Two university hospital programs. PATIENTS: Thirty-eight patients with
      symptomatic pleural effusions associated with malignancy. INTERVENTIONS: A 14F
      catheter was inserted percutaneously into the pleural space after radiographic
      confirmation of free fluid by lateral decubitus views. Following radiographic
      confirmation of complete fluid evacuation, a sclerosing agent (ie, talc slurry or
      bleomycin) was instilled into the pleural space. This was accomplished within 2 h
      of chest tube insertion, unless the tube was inserted in the evening or if the
      lung was trapped. After clamping the tube for 90 min, the pleural space was
      drained for 2 h, after which the chest tube was removed. The intervention was
      scored as "successful" if no radiographic evidence of fluid reaccumulation was
      noted at 4 weeks. A "partial successful" score indicated reaccumulation of fluid
      that did not produce symptoms and did not require repeat pleural drainage of any
      sort. All other outcomes were scored as "unsuccessful." MEASUREMENTS AND RESULTS:
      Forty chest tubes were inserted into 38 patients. Four procedures revealed the
      presence of a trapped lung and did not result in any attempt at pleurodesis. Five
      patients who received pleurodesis died in less than 1 month and therefore were
      not evaluable. Two patients had technical problems with the chest tube and were
      not evaluable. Of the remaining 29 procedures, drainage procedures with
      pleurodesis were performed in 27 patients, a complete response was seen in 14
      patients (48%), a partial response was seen in 9 patients (31%), and 6 patients
      (21%) did not respond to pleurodesis. Chemical pleurodesis was completed as an
      outpatient procedure in only two patients. In one of these, the outcome was
      unsuccessful. In the remainder, insertion of the chest tube in the evening or
      additional medical problems necessitated hospital admission, but the entire
      procedure was completed within 24 h. CONCLUSIONS: Chemical pleurodesis can be
      accomplished with good results in < 24 h in the majority of patients with
      malignant pleural effusions.

PMID- 12796166
TI  - Evaluating the use of a portable spirometer in a study of pediatric asthma.
AB  - STUDY OBJECTIVES: Laboratory-based spirometry is the "gold standard" for the
      assessment of lung function, both in clinical and research protocols. These
      spirometers, however, are neither practical nor affordable for home-based
      monitoring or studies that collect data in multiple locations. Traditionally,
      peak flowmeters have been used, but they have important limitations. DESIGN:
      Based on data from a cohort of 92 children with asthma, we evaluated the
      agreement between a portable spirometer and a office-based spirometer, using an
      in-line technique to evaluate measures from the same effort. We compared a range
      of pulmonary function parameters collected during office-based tests, and also
      evaluated whether adequate adherence and data quality could be achieved in a home
      based study of children with asthma. RESULTS: The agreement between the devices
      for the actual values of peak expiratory flow, FEV(1), and forced expiratory flow
      at 25% of FVC was excellent. The portable device was programmed with customized
      software to grade each curve using revised American Thoracic Society
      acceptability and reproducibility criteria. For 74% of the curves, quality grade
      agreed with a grade assigned by physician review of the curve from the office
      based spirometer. During 2 weeks of twice-daily monitoring at home, children
      completed an average of 23 of 28 possible sessions (83%). Of these, 84% had at
      least two acceptable and two reproducible curves. Although children >or= 8 years
      old were not more adherent, they were significantly more likely to achieve
      acceptable and reproducible curves. CONCLUSIONS: Portable spirometers can provide
      measurements that are highly comparable to those obtained from "gold standard"
      laboratory spirometers, and high-quality tracings can be achieved both at home
      and in the office setting. Visual inspection of the curves by experienced
      reviewers identified unacceptable curves that were not rejected by the quality
      control software. Portable spirometers are an important contribution to
      epidemiologic and clinical studies that require frequent measures of a more broad
      range of pulmonary function parameters than can be provided by peak flowmeters.

PMID- 12796167
TI  - Triple inhaled drug protocol for the treatment of acute severe asthma.
AB  - STUDY OBJECTIVE: This study tests the hypothesis that the administration of
      multiple doses of inhaled albuterol (A), ipratropium bromide (IB), and
      flunisolide (F) provides an additional benefit to adults with acute severe asthma
      compared with the administration of A plus IB (A/IB) or A plus F (A/F). DESIGN:
      Randomized, double-blind, prospective trial. PATIENTS AND INTERVENTIONS: One
      hundred seventy-two patients who presented to an emergency department were
      assigned to receive A, IB, and F (ie, triple drug treatment [TDG]; 56 patients),
      A/IB (60 patients), or A/F (56 patients). All drugs were administered through a
      metered-dose inhaler and spacer at 10-min intervals for 3 h. RESULTS: Patients
      who received TDG had an overall 64% greater improvement (95% confidence interval
      [CI], 24 to 103%; p = 0.002) in FEV(1) (mean [+/- SD], 2.1 +/- 0.6 L) than those
      who received A/F (mean, 1.7 +/- 0.6 L), and a 41% greater improvement (95% CI, 1
      to 80%; p = 0.04) than those who received A/IB (mean, 1.8 +/- 0.6 L). Differences
      between groups increased with time (p = 0.001). At 3 h, there was a trend toward
      a reduction in hospital admission rates (A/IB group, 25%; A/F group, 20%; and TDG
      group, 11%). The patients who were the most likely to benefit (ie, those with a
      greater improvement in pulmonary function and a significant reduction in the
      hospitalization rate) from TDG were those with more severe obstruction (ie,
      FEV(1), < 30% of predicted). The benefit of TDG was equally evident independent
      of the patient's previous use of corticosteroids. CONCLUSIONS: The data suggest
      that there was a therapeutic benefit from the addition of IB and F to A
      administered in high doses, particularly in those patients in whom the FEV(1) was
      < 30% of the predicted value.

PMID- 12796168
TI  - Diagnosis of airflow limitation combined with smoking cessation advice increases
      stop-smoking rate.
AB  - OBJECTIVES: To assess how the diagnosis of airflow limitation (AL) combined with
      advice to stop smoking in middle-aged smokers influence the smoking cessation
      rate and to identify predictors of successful outcome. DESIGN: Prospective,
      single-center, comparative study of the effects of smoking intervention in
      smokers with diagnosed AL and in smokers with normal lung function (NLF).
      SETTING: University hospital, out-patient clinic. PARTICIPANTS: Of 659 smokers
      participating in a population spirometric screening for COPD combined with
      smoking cessation advice, 558 (AL, 297 smokers; NLF, 261 smokers) were invited
      for a follow-up after 1 year. INTERVENTION: At follow-up, spirometry was repeated
      and smoking status was assessed. Nonsmoking status was validated with carbon
      monoxide measurements in exhaled air. Patients who did not come for the follow-up
      visit were considered to be smokers. RESULTS: Of 558 smokers invited, 368 (66%)
      presented for the follow-up visit. All had tried to reduce their smoking habit.
      The number of cigarettes smoked per day (cpd) at 1 year was - 5.2 (p < 0.01) in
      patients with AL and - 2.7 (not significant [NS]) in those with NLF. The 1-year
      cessation rate in smokers with AL was 10.1% vs 8.4% in smokers with NLF (NS).
      After stratifying the patients according to AL severity, the highest cessation
      rate was observed in smokers with moderate and severe AL (16.5%) compared to
      smokers with mild AL (6.4%; p < 0.001) and smokers with NLF (8.4%; p < 0.05). In
      a univariate analysis, the cessation of smoking was correlated with older age (p
      < 0.001), later age when starting smoking (p < 0.005), lower tobacco exposure (in
      pack-years; p < 0.01), fewer cpd (p < 0.001), and lower lung function (p < 0.05).
      No interaction effect was observed for any of the studied variables using two-way
      analysis of variance. In a stepwise logistic regression analysis, age (p <
      0.001), tobacco exposure (in pack-years; p < 0.001), and FEV(1) percent predicted
      (p < 0.01) proved to be significant predictors of success in stopping smoking.
      CONCLUSION: All smokers, irrespective of their lung function, tried to modify
      their habit as the result of screening for COPD combined with smoking cessation
      advice. The diagnosis of AL motivated smokers to attempt to quit smoking. Older
      age, lower tobacco exposure, and lower lung function were the predictors of
      success in quitting smoking.

PMID- 12796169
TI  - Prevalence and correlates of airway obstruction in a community-based sample of
      adults.
AB  - BACKGROUND: Virtually all the information available on the prevalence of
      obstructive airway disease is from Western countries. There are no data from
      Korea, and reports from other regions of Asia are poorly documented. OBJECTIVES:
      To evaluate the prevalence and correlates of airway obstruction in a community
      based setting in Korea. DESIGN: A cross-sectional, population-based study.
      SETTING: Ansan City, near Seoul, South Korea. PARTICIPANTS: A sample of 1,160
      community-dwelling men and women aged >or= 18 years (73.1% of the men and 4.1% of
      the women were either current or former smokers). MEASUREMENTS: Subjects
      underwent physical examinations following a standardized protocol. Data on
      demographic and health-related factors also were collected. Pulmonary function
      testing was administered according to American Thoracic Society (ATS)
      recommendations. RESULTS: The prevalence of airway obstruction was 10.3% (men,
      17%; women, 5.6%) by ATS criteria. Ninety percent of the cases of airway
      obstruction were mild in degree. Twenty percent of male current smokers had
      airway obstruction. After adjusting for age, gender, and alcohol consumption, the
      odds of disease was 3.2 times greater in subjects who had smoked for >or= 20 pack
      years vs never smokers (95% confidence interval [CI], 1.7 to 6.2). The adjusted
      odds of disease were 4.3-fold higher in subjects >or= 45 years of age vs those
      who were younger (95% CI, 2.6 to 7.0). CONCLUSIONS: Since airway obstruction is
      strongly related to age and smoking, the prevalence of obstructive airway disease
      in countries like Korea, where the population is rapidly aging and cigarette
      smoking is on the rise among younger individuals (particularly among women), can
      be expected to increase. Further efforts to diagnose early obstructive airway
      disease and to prevent or delay its onset should be emphasized as a major public
      health concern.

PMID- 12796170
TI  - Severe gastroesophageal reflux is associated with reduced carbon monoxide
      diffusing capacity.
AB  - OBJECTIVE: To assess whether severe gastroesophageal reflux (GER) is associated
      with abnormalities in lung function including measures of lung volume and gas
      diffusion. METHODS: Data from 147 patients with obesity (body mass index [BMI]
      range, 31.7 to 70 kg/m(2)) who presented for obesity surgery was analyzed
      retrospectively. A questionnaire was completed preoperatively that included a
      history of GER, frequency and severity of symptoms, investigations, and
      medications used. A history of lung disease, sleep-disordered breathing, and
      smoking also was obtained. A physician who was blinded to lung function graded
      GER severity prospectively by the results of pH monitoring and/or gastroscopy,
      and medication use. Spirometry, lung volumes, and gas transfer were measured
      preoperatively. RESULTS: Patients with severe GER had reduced levels of the
      diffusing capacity of the lung for carbon monoxide (DLCO) [21.1 mL/min/mm Hg; 95%
      confidence interval (CI), 18.9 to 23.2], as measured by CO transfer, compared
      with those patients without GER (26.3 mL/min/mm Hg; 95% CI, 24.4 to 28.2; p =
      0.001). This remained significant after adjusting for age, gender, BMI, and
      smoking history. Gas transfer corrected for lung volume also was reduced in the
      group with severe GER (4.6 mL/min/mm Hg per L; 95% CI, 4.3 to 4.9) compared to
      the group without GER (5.3 mL/min/mm Hg per L; 95% CI, 5.1 to 5.5; p = 0.001).
      There was no significant difference in other measures of lung function.
      CONCLUSIONS: Severe GER is associated with an impairment of gas exchange. This
      may be due to microaspiration of gastric acid or fluid into the airways.

PMID- 12796171
TI  - A spirometry-based algorithm to direct lung function testing in the pulmonary
      function laboratory.
AB  - OBJECTIVE: To design a spirometry-based algorithm to predict pulmonary
      restrictive impairment and reduce the number of patients undergoing unnecessary
      lung volume testing. DESIGN: Two prospective studies of 259 consecutive patients
      and 265 consecutive patients used to derive and validate the algorithm,
      respectively. SETTING: A pulmonary function laboratory of a tertiary care
      hospital. PATIENTS: Consecutive adults referred to the laboratory for lung volume
      measurements and spirometry. MEASUREMENTS: The sensitivity of the algorithm for
      predicting pulmonary restriction and the cost savings associated with its use.
      RESULTS: Total lung capacity correlated strongly with FVC (r = 0.66) and showed
      an inverse correlation with the FEV(1)/FVC ratio (r = - 0.41). According to the
      algorithm, only patients with an FVC < 85% of predicted and an FEV(1)/FVC ratio
      >or= 55% required lung volume measurements following spirometry. The algorithm
      had a high sensitivity for predicting restriction and a high negative predictive
      value (NPV) for excluding restriction (sensitivity, 96%; NPV, 98%). The
      diagnostic properties of the algorithm were reproducible in the validation study.
      Application of the algorithm would eliminate the need for lung volume testing in
      48 to 49% of patients referred to the pulmonary function test (PFT) laboratory,
      reducing costs by 33%. CONCLUSIONS: A spirometry-based algorithm accurately
      excludes pulmonary restriction and reduces unnecessary lung volume testing in the
      PFT laboratory almost in half.

PMID- 12796172
TI  - Cardiac troponin T monitoring identifies high-risk group of normotensive patients
      with acute pulmonary embolism.
AB  - STUDY OBJECTIVES: Indications for thrombolysis in normotensive patients with
      pulmonary embolism (PE), based on the presence of right ventricular (RV) overload
      during transthoracic echocardiography (TTE), are controversial. We checked
      whether the monitoring of cardiac troponin T (cTnT) might help in risk
      stratification by detecting patients with RV myocardial injury. PATIENTS AND
      DESIGN: We studied 64 normotensive patients (30 women and 34 men) with a mean (+/
      SD) age of 61.3 +/- 17 years and PE, who had undergone TTE for the assessment of
      RV overload. Plasma cTnT levels were measured quantitatively (detection limit, >
      0.01 ng/mL) at hospital admission, and subsequently three times at 6-h intervals.
      Heparin therapy alone was used in 87.5% of patients, while 12.5% of patients
      received thrombolysis. RESULTS: cTnT was detected in 50% of patients. All eight
      in-hospital deaths occurred in the troponin-positive group, however, in one case
      the results of the first three assays had been negative. Elevated plasma cTnT
      increased the risk of PE-related death (odds ratio [OR], 21; 95% confidence
      interval [CI], 1.2 to 389). Increased age and elevated tricuspid regurgitant jet
      velocity, but not RV diameter/left ventricle diameter ratio, influenced the
      hospital mortality rate. Increased cTnT level was the only parameter predicting
      15 in-hospital clinical adverse events (ie, death, thrombolysis, cardiopulmonary
      resuscitation, and IV use of catecholamine agents) [OR, 24.1; 95% CI, 2.9 to
      200]. CONCLUSIONS: Patients with PE and elevated cTnT levels detected during
      repetitive assays are at a significant risk of a complicated clinical course and
      fatal outcome.

PMID- 12796173
TI  - Upper extremity deep venous thrombosis.
AB  - PURPOSE: To determine the prevalence of symptomatic upper extremity deep venous
      thrombosis (DVT) and its association with symptomatic acute pulmonary embolism
      (PE) in a community teaching hospital. METHODS: The prevalence of symptomatic
      upper extremity DVT was evaluated retrospectively at a community teaching
      hospital during the 2-year period between July 1, 1998, and June 30, 2000.
      Patients were identified by International Classification of Disease, ninth
      revision, clinical modification, discharge codes and a review of the records of
      all compression Doppler ultrasonograms, venograms of the upper extremities, and
      magnetic resonance angiograms of the upper extremities. RESULTS: Symptomatic
      upper extremity DVT was diagnosed in 65 of 44,136 patients of all ages (0.15%)
      [or 64 of 34,567 adult patients >or= 20 years of age; 0.19%]. In seven patients,
      the upper extremity DVT was shown by venography to extend proximally to the
      brachiocephalic vein. Among these, the DVT extended to the superior vena cava in
      two. All of the patients received anticoagulant therapy for upper extremity DVT.
      No patients developed symptomatic PE. Central lines at the site of the upper
      extremity DVT were inserted in 39 of 65 patients (60%). Cancer was diagnosed in
      30 of 65 patients (46%), 23 cancer patients also had central lines, and 19
      patients (29%) had upper extremity DVT with no apparent cause. All patients had
      swelling of the upper extremities. Erythema over the affected site was present in
      four patients (6%). Pain was present in 26 patients (40%), although some
      discomfort due to swelling was present in all patients. CONCLUSION: Symptomatic
      upper extremity DVT is not uncommon in hospitalized patients. Symptomatic PE
      resulting from upper extremity DVT was not observed in these patients, all of
      whom were treated with anticoagulants.

PMID- 12796174
TI  - Feasibility of simplifying balloon mitral valvuloplasty by obviating left-sided
      cardiac catheterization using on-line guidance with transesophageal
      echocardiography.
AB  - STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of
      simplifying balloon mitral valvuloplasty through the obviation of left-sided
      cardiac catheterization using on-line guidance with transesophageal
      echocardiography in patients with mitral stenosis. SETTING: A tertiary care
      medical center DESIGN: Patients who were eligible for balloon mitral
      valvuloplasty were enrolled into the study if they had no evidence of ischemic
      heart disease. Sixty-six patients (50 women and 16 men) met the criteria. Balloon
      mitral valvuloplasty was performed through right-sided cardiac catheterization
      using adjunctive on-line guidance with transesophageal echocardiography. Left
      sided catheterization was obviated. MEASUREMENT AND RESULTS: Balloon mitral
      valvuloplasty was smoothly performed in all patients. Successful dilatation
      (postprocedural mitral orifice area, > 1.5 cm(2); or increment in mitral orifice
      area, >or= 50%) was achieved in 50 patients (75.8%). The mean (+/- SD) mitral
      orifice area increased from 1.08 +/- 0.23 cm(2) to 1.68 +/- 0.39 cm(2) (p =
      0.0000). There were no in-hospital deaths, no patients with cardiac tamponade, or
      complications necessitating an emergency cardiac operation. The mean fluoroscopy
      time was 7.6 +/- 3.9 min, and the total procedure time was 50.2 +/- 15.0 min.
      CONCLUSION: It is feasible and safe to simplify balloon mitral valvuloplasty by
      obviating left-sided cardiac catheterization in selected patients with mitral
      stenosis using adjunctive on-line guidance with transesophageal echocardiography.

PMID- 12796175
TI  - Risk of mortality and heart failure exacerbations associated with inhaled beta
      adrenoceptor agonists among patients with known left ventricular systolic
      dysfunction.
AB  - OBJECTIVES: Recent studies suggest that myocardial beta(2)-adrenoceptors may be
      important in chronic heart failure. We sought to determine if use of selective
      beta(2)-agonists was associated with hospitalization for heart failure and all
      cause mortality. METHODS: We studied a cohort of patients with left ventricular
      systolic dysfunction (LVSD). The outcome was the first hospitalization with a
      primary diagnosis of chronic heart failure or death from any cause. The exposure
      was the average number of beta-agonist canisters filled per month in the 90 days
      prior to and 15 days after enrollment. RESULTS: Among 1,529 subjects, the
      relative risk (RR) of chronic heart failure hospital admission associated with
      inhaled beta-agonists followed a dose-response relationship: RR for one canister
      per month, 1.4 (95% confidence interval [CI], 0.9 to 2.0), RR for two canisters
      per month, 1.7 (95% CI, 1.2 to 2.5), and RR for three canisters per month, 2.1
      (95% CI, 1.4 to 3.1). The RR of death demonstrated a similar finding: RR for one
      canister per month, 0.9 (95% CI, 0.5 to 1.5), RR for two canisters per month, 1.3
      (95% CI, 0.9 to 2.1), and RR for three canisters per month, 2.0 (95% CI, 1.3 to
      3.1). Adjusting for potential confounding factors did not affect the estimates.
      CONCLUSION: Among subjects with LVSD, inhaled beta-agonists were associated with
      an increased risk of heart failure hospitalization, and all-cause mortality.
      Clinicians should carefully consider the etiology of dyspnea when prescribing
      beta-agonists to patients with LVSD.

PMID- 12796176
TI  - Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV
      infected patients: a multicenter study of 67 cases.
AB  - OBJECTIVE: To assess the clinical characteristics and the factors that influenced
      the prognosis of patients with HIV and infection caused by Rhodococcus equi.
      DESIGN: Observational, multicenter study in 29 Spanish general hospitals.
      SETTING: These hospitals comprised a total of 20,250 beds for acute patients and
      served a population of 9,716,880 inhabitants. PATIENTS: All patients with HIV and
      diagnosed R equi infection until September 1998. RESULTS: During the study
      period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included
      (55 male patients; mean +/- SD age, 31.7 +/- 5.8 years). At the time of diagnosis
      of R equi infection, the mean CD4+ lymphocyte count was 35/ micro L (range, 1 to
      183/ micro L) and the stage of HIV infection was A3 in 10.4% of patients, B3 in
      31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in
      sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%).
      Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were
      observed in all of them, with cavitations in 45 patients. The most active
      antibiotics against the strains isolated were vancomycin, amikacin, rifampicin,
      imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 +/-
      12.8 months, 23 patients (34.3%) died due to causes related to R equi infection
      and 6 other patients showed evidence of progression of the infection. The absence
      of highly active antiretroviral therapy (HAART) was independently associated with
      mortality related to R equi infection (relative risk, 53.4; 95% confidence
      interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher
      than that of patients who did not receive this therapy. CONCLUSIONS: Infection by
      R equi is an infrequent, opportunistic complication of HIV infection and occurs
      during advanced stages of immunodepression. In these patients, it leads to a
      severe illness that usually causes a bacteremic, cavitary pneumonia, although
      HAART can improve the prognosis.

PMID- 12796178
TI  - The pulmonary effects of long-term exposure to aerosol pentamidine: a 5-year
      surveillance study in HIV-infected patients.
AB  - STUDY OBJECTIVES: To assess the effects of long-term exposure to aerosolized
      pentamidine (AP) for the prophylaxis of Pneumocystis carinii pneumonia on the
      pulmonary function. DESIGN: The results of pulmonary function tests (PFTs) over a
      period of 5 years were retrospectively analyzed in a cohort of HIV-infected
      individuals. SETTING: A government-funded AP clinic in a large metropolitan
      center in Canada. PATIENTS: Among the cohort of 1,850 HIV-positive patients who
      received regular AP prophylaxis between 1989 and 2001 at the AP clinic, 83
      received AP for >or= 5 years. Of these 83 patients, baseline and long-term follow
      up PFT data were available for 79. These subjects formed the study population for
      this analysis. RESULTS: The cohort was divided according to smoking status
      (smokers, 48%). The rate of decline of FEV(1) in the smokers over the 5-year
      period was statistically significant but was comparable to that expected of
      healthy smokers. As for the nonsmokers, there was no significant reduction in
      FEV(1). Flow rates at low lung volumes (ie, forced expiratory flow at 50% and 75%
      of FEV(1)) and low FEV(1)/FVC ratios showed significant declines in both smokers
      and nonsmokers. On the other hand, no significant changes in FVC, total lung
      capacity, residual volume, or diffusing capacity of the lung for carbon monoxide
      were observed. The apparent slight reduction in flow rates seems to be at the
      level of the small airways. CONCLUSIONS: The PFT data suggest that AP can be well
      tolerated over a 5-year period in HIV-infected patients with only modest
      reduction in flow rates at the level of the small airways, especially in smokers.

PMID- 12796177
TI  - Respiratory symptoms among HIV-seropositive individuals.
AB  - STUDY OBJECTIVES: Recent evidence suggests that chronic or latent viral infection
      may be an important predisposing factor in the development of COPD among smokers.
      As such, understanding if HIV-seropositive smokers are at heightened risk for
      respiratory symptoms may have relevance with regard to COPD pathogenesis. The
      current study was done to systematically identify the prevalence of respiratory
      symptoms among an HIV-seropositive population and to identify associated clinical
      features. DESIGN AND SETTING: Cross-sectional analysis at an academic medical
      center. PARTICIPANTS: Three hundred twenty-seven HIV-seropositive individuals
      without a history of AIDS-related pulmonary complications. Fifty-two HIV-negative
      individuals with a similar age and smoking history served as a comparison group.
      MEASUREMENTS: Administration of the American Thoracic Society Division of Lung
      Diseases respiratory questionnaire, and pulmonary function studies. RESULTS:
      Respiratory symptoms including dyspnea (41.6% vs 7.7%), cough (40% vs 25%), and
      phlegm production (41.9% vs 23.1%) were extremely common in the HIV-group and
      significantly more common than in the HIV-negative group. Current or prior
      cigarette smoking was the most important predictor of respiratory symptoms among
      the HIV-seropositive group. The use of the antiretroviral agent lamivudine was
      associated with a significant reduction in dyspnea. CONCLUSION: HIV-seropositive
      individuals are at increased risk for the development of respiratory symptoms
      even prior to the onset of AIDS-related pulmonary complications. This may reflect
      a heightened susceptibility to the effects of cigarette smoking.

PMID- 12796179
TI  - The effect of pulmonary rehabilitation in patients with post-tuberculosis lung
      disorder.
AB  - STUDY OBJECTIVES: Although the benefit of pulmonary rehabilitation (PR) has been
      demonstrated for patients with COPD, the benefit for patients with non-COPD lung
      disorders is still unclear. In the present study, we compared the effect of PR on
      patients with post-tuberculosis (TBC) lung disorders and patients with COPD.
      DESIGN: We performed a prospective nonrandomized open trial over a 9-week period.
      PATIENTS AND METHODS: Thirty-two patients with post-TBC lung disorders
      (thoracoplasty, 25 patients; mean [+/- SD] age, 71 +/- 5 years; FEV(1), 0.84 +/-
      0.29 L) and 32 age-matched and FEV(1)-matched COPD patients were enrolled in the
      study. First, we compared the exercise tolerance between groups using a 6-min
      walking test. Next, we trained the patients using a 9-week outpatient PR program.
      We assessed improvement using clinical dyspnea ratings, a daily activity score,
      and the results of a 6-min walking test. RESULTS: When age and FEV(1) were
      matched, the distance covered during the 6-min walking test did not differ
      between the groups. After rehabilitation, significant improvement was observed in
      both the post-TBC group and the COPD group in terms of Medical Research Council
      dyspnea grade, transition dyspnea index, activity score, and 6-min walking
      distance (42 m [p < 0.01] vs 47 m [p < 0.01], respectively). The magnitudes of
      the improvement in these parameters were comparable between the groups.
      CONCLUSIONS: PR is as beneficial in post-TBC lung disorder patients as in COPD
      patients if the severity of the disability is similar.

PMID- 12796180
TI  - Functional sequelae of tuberculous pleurisy in patients correctly treated.
AB  - STUDY OBJECTIVES: To assess the functional sequelae (FS) of patients with
      tuberculous pleurisy (TP), to analyze the influence of different factors in the
      occurrence of these FS, and, finally, to evaluate the relationship between the FS
      and roentgenographic sequelae. DESIGN: An observational, retrospective study.
      SETTING: A community teaching hospital in Alicante, Spain. PATIENTS AND METHODS:
      From April 1986 to July 2000, all patients with a firmly established diagnosis of
      TP, who had been functionally studied at the end of follow-up, were included in
      the study. A diagnosis of TP was considered to be definitive when the presence of
      granuloma on a pleural biopsy specimen was demonstrated or when a culture was
      positive for Mycobacterium tuberculosis in pleural fluid (PF) or tissue. The
      general characteristics of the study population and PF were compared in patients
      with or without restrictive FS (ie, FVC or TLC < 80%), looking for risk factors
      for developing this complication. RESULTS: Eighty-one of 150 patients who had
      been treated for TP were eligible for the study. At the end of follow-up, eight
      patients (10%) had a restrictive FS. These patients had a lower PF lactate
      dehydrogenase concentration (p < 0.001), a higher PF concentration of cholesterol
      (p < 0.03) and triglycerides (p < 0.03), and a higher percentage of lymphocytes
      (p < 0.04). A weak correlation was found between the FVC and the intensity of
      radiographic pleural thickening (r = - 0.298; p < 0.01). CONCLUSIONS: The FS in
      patients with TP is restrictive in type, infrequent, and usually mild. A higher
      PF lipid content or a more chronic inflammatory pleural reaction at diagnosis
      appear to be risk factors for developing a FS. The correlation between FS and
      roentgenographic sequelae is poor.

PMID- 12796181
TI  - Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases.
AB  - STUDY OBJECTIVE: Cytokeratin 19 fragment (CYFRA) is a specific tumor marker in
      patients with lung cancer; however, it has been reported that serum CYFRA levels
      are elevated in some patients with nonmalignant respiratory diseases such as
      interstitial pulmonary fibrosis (IPF) and collagen disease-associated pulmonary
      fibrosis (CDPF). To investigate the serum CYFRA levels in nonmalignant
      respiratory diseases in detail, we studied 413 patients with respiratory
      diseases. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS:
      Four hundred thirteen patients with nonmalignant respiratory diseases and lung
      cancer. MEASUREMENTS AND RESULTS: Serum CYFRA levels were measured with a
      commercially available enzyme immunoassay kit. Immunohistochemical study was
      performed using monoclonal antibody Ks 19.1 (Rosch Diagnosica; Bern, Switzerland)
      on surgically resected or autopsied lung specimens. Gel electrophoresis and
      immunoblotting was performed with serum samples. In 149 patients with
      nonmalignant diseases except IPF and CDPF, the ratio of patients with > 3.5 ng/mL
      of serum CYFRA was 13.4%. In 13 of 30 patients (43.3%) with IPF and CDPF, the
      serum CYFRA levels were abnormally elevated. The 95th percentile serum CYFRA
      level of the patients with nonmalignant respiratory diseases was 6.2 ng/mL, and
      none of them had CYFRA levels > 20.3 ng/mL. Survival in patients with IPF and
      CDPF with elevated serum CYFRA levels were significantly lower than in those with
      normal range (p = 0.0335). Western blotting using serum from nonmalignant lung
      diseases and patients with lung cancer showed no apparent difference between
      them. An immunohistochemical study indicated CYFRA was selectively expressed in
      the pulmonary epithelial cells that covered the remodeling alveolar septi in
      nonmalignant respiratory disease. CONCLUSION: Serum CYFRA was elevated in some
      nonmalignant respiratory diseases, especially in IPF and CDPF. The value of serum
      CYFRA would reflect the severity of lung injury in nonmalignant respiratory
      diseases and might be related to the prognosis in patients with IPF and CDPF.

PMID- 12796182
TI  - Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis.
AB  - STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal
      lung disease of unknown etiology. The incidence of IPF increases with age. Aging
      contributes to lifestyle-related diseases, including diabetes mellitus (DM);
      therefore, it is possible that lifestyle-related diseases may affect either the
      initiation or progression of IPF. DESIGN: Case-control study. SETTING: Nippon
      Medical School and Omiya City Clinic. PATIENTS AND PARTICIPANTS: Sixty-five
      consecutive patients with IPF who were admitted to Nippon Medical School Hospital
      from 1995 to 2000, and 184 control subjects selected from 15,798 subjects who
      were admitted to Omiya City Clinic for routine medical examination between
      September 1999 and August 2000. MEASUREMENTS: Age, sex, smoking history, and
      results of physical examinations, blood examinations, and lung function testing
      were extracted from medical records and were compared with the diagnostic
      criteria for lifestyle-related diseases. RESULTS: The adjusted odds ratios for
      cigarette smoking were 5.40 (95% confidence interval [CI], 2.30 to 12.66) and
      4.06 (95% CI, 1.80 to 9.15) for diabetes. There were no differences in clinical
      characteristics of patients with IPF that could be related to the presence of DM.
      CONCLUSION: DM may be a risk factor for IPF.

PMID- 12796183
TI  - Osteoporosis in pulmonary clinic patients: does point-of-care screening predict
      central dual-energy X-ray absorptiometry?
AB  - STUDY OBJECTIVES: Patients in a pulmonary clinic have disorders that predispose
      them to osteoporosis and may use glucocorticoid therapy, which has been
      associated with low bone mineral density (BMD) and increased fracture risk.
      Ideally, all patients at risk for osteoporosis would be screened using the best
      test available, which is central BMD by dual-energy x-ray absorptiometry (DXA).
      We proposed to stratify the risk for osteoporosis by the use of a simple
      questionnaire and point-of-care heel ultrasound BMD measurements. DESIGN: Cross
      sectional screening study. SETTING: Pulmonary clinic in a single Veterans Affairs
      Medical Center. PATIENTS: Approximately 200 male and female patients who had not
      had previous BMD testing were eligible for the study, and 107 gave consent.
      INTERVENTIONS: One hundred seven men (white, 71 men; black, 35 men; and Asian, 1
      man) underwent heel BMD testing and filled out a questionnaire. Ninety-eight men
      underwent a central DXA. RESULTS: Of 98 subjects, 24.5% had a spine, total hip,
      or femoral neck (FN) T-score of <or= -2.5, which is the generally accepted
      definition of osteoporosis diagnosed using DXA, and 44.9% had a T-score of <or= 
      2.0. The best-fit models for predicting FN or total hip BMD included body weight,
      heel BMD, corticosteroid use for >or= 7 days, and race, which accounted for 52 to
      57% of the variance. When a heel ultrasound T-score of -1.0 was tested to predict
      a central DXA T-score of -2.0, the sensitivity was 61% and the specificity 64%.
      Adding the questionnaire score and body mass index (BMI) to the heel T-score
      improved sensitivity but not specificity. Moreover, BMI and age predicted central
      BMD with similar sensitivity and specificity. Importantly, of 24 patients with a
      central DXA T-score of <or= -2.5, only 14 were identified by a heel T-score of
      <or= -1.0. CONCLUSIONS: Although the findings from a heel ultrasound plus the
      answers to a questionnaire were reasonably good indicators for predicting the
      presence of low BMD, little predictability was gained over the use of BMI and
      age. In a group of pulmonary clinic patients, the prevalence of osteoporosis was
      clinically significant, and central DXA testing was the preferable technique for
      identifying patients who were at risk for fracture.

PMID- 12796184
TI  - Variation in diaphragm position and shape in adults with normal pulmonary
      function.
AB  - BACKGROUND: Diaphragm position and shape on chest radiographs are routinely used
      as indicators of normal or abnormal lung volume. However, previous population
      studies of normal diaphragm position and shape frequently lack objective
      radiographic measurements and documentation of pulmonary function, and do not
      account for the observed variability. STUDY OBJECTIVE: s: To determine the
      spectrum of diaphragm position and shape on chest radiographs using objective
      measurements, in patients with normal pulmonary function, and to identify the
      relationship of diaphragm position and shape to demographic variables and
      radiographic thoracic dimensions. DESIGN: Prospective cross-sectional
      observational study. SETTING: University hospital. PATIENTS: One hundred fifty
      three adults with normal FEV(1) (>or= 80% predicted) and normal total lung
      capacity (80 to 120% predicted). MEASUREMENTS AND RESULTS: Diaphragm position and
      shape relative to anatomic landmarks were determined from posteroanterior and
      lateral chest radiographs. We used descriptive statistics to calculate normal
      values, and linear correlation, two-tailed t tests, and multivariate analysis to
      relate findings to age, weight, gender, and thoracic dimensions. The right
      hemidiaphragm dome was positioned at 9.7 +/- 0.8 thoracic vertebral levels (body
      plus disk space) [mean +/- SD] below the top of the first thoracic vertebra
      (range, 7.4 to 11.3 vertebral levels), and the left hemidiaphragm dome was
      positioned at 10.2 +/- 0.8 vertebral levels (range, 8.1 to 11.8 vertebral
      levels). The right hemidiaphragm radius was 13.8 +/- 3.8 cm (range, 7.2 to 29.6
      cm), and the ratio between the height and the anteroposterior dimension of the
      right hemidiaphragm was 0.23 +/- 0.05 cm (range, 0.08 to 0.36 cm). The diaphragm
      tended to be lower with higher age, lower weight, and smaller transverse and
      anteroposterior thoracic dimensions (r = 0.22 - 0.47, p < 0.05), and flatter
      (larger radius) with higher age, weight, transverse thoracic dimension, pack
      years smoked (r = 0.32 - 0.42, p < 0.0001), and male gender (p < 0.0001). The
      tested variables accounted for approximately one third of the variability in
      diaphragm position and shape (multivariate R(2) = 0.31 - 0.38). CONCLUSIONS: The
      substantial variability in normal diaphragm position and shape is related to
      weight, age, and thoracic dimensions. Consideration of these factors may be
      useful when evaluating chest radiographs.

PMID- 12796185
TI  - Impedance cardiography: the next vital sign technology?
AB  - OBJECTIVE: To evaluate the following: (1) the intramethod variability of
      impedance cardiography (ICG) cardiac output (CO) measurements via the latest
      generation monitor and thermodilution CO measurements (CO-TDs); (2) the
      intermethod comparison of ICG CO and CO-TD; and (3) comparisons of the
      intergeneration ICG CO equation to CO-TD, using the latest ICG CO equation, the
      ZMARC (CO-ICG), and the predecessor equations for measuring the ICG CO of Kubicek
      (CO-K), Sramek (CO-S), and Sramek-Bernstein (CO-SB). DESIGN: Prospective study.
      SETTING: A cardiovascular-thoracic surgery ICU in a community university
      affiliated hospital. PATIENTS: Post-coronary artery bypass graft patients (n =
      53) in whom 210 pairs of CO measurements were made. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The CO-ICG was determined simultaneously while the
      nurse was performing the CO-TD. Variability within the monitoring method was
      better for CO-ICG compared to CO-TD (6.3% vs 24.7%, respectively). The
      correlation, bias, and precision of the CO-ICG was good compared to CO-TD (r(2) =
      0.658; r = 0.811; bias, -0.17 L/min; precision, 1.09 L/min; CO-ICG = 1.00 x CO-TD
      - 0.17; p < 0.001). A steady improvement in agreement of the previous ICG
      methodologies compared to CO-TD was observed as follows: (1) CO-K: r(2) = 0.309;
      r = 0.556; bias, -1.71 L/min; precision, 1.81 L/min; CO-K = 0.78 x CO-TD - 0.45;
      p < 0.001; (2) CO-S: r(2) = 0.361; r = 0.601; bias, -1.46 L/min; precision, 1.63
      L/min; CO-S = 0.80 x CO-TD - 0.36; p < 0.001; and (3) CO-SB: r(2) = 0.469; r =
      0.685; bias, -0.77 L/min; precision, 1.69 L/min; CO-SB = 1.03 x CO-TD - 0.95; p <
      0.001. The CO-ICG demonstrated the closest agreement to CO-TD. CONCLUSION: The
      latest ICG technology for determining CO (CO-ICG) is less variable and more
      reproducible in an intrapatient sense than is CO-TD, it is equivalent to the
      average accepted CO-TD in post-coronary artery bypass graft patients, and showed
      marked improvement in agreement with CO-TD compared to measurements made using
      previous generation ICG CO equations.

PMID- 12796186
TI  - Hospital-acquired pneumonia: risk factors for antimicrobial-resistant causative
      pathogens in critically ill patients.
AB  - STUDY OBJECTIVES: To determine factors associated with antimicrobial-resistant
      hospital-acquired pneumonia (AR-HAP), to build an algorithm evaluating the risk
      for such a pneumonia, and to test this algorithm. DESIGN: Combined observational
      and validation cohorts over two periods: January 1994 to December 1999, and
      January 2000 to March 2001. SETTING: One ICU from a university-affiliated urban
      teaching hospital. PATIENTS: One hundred twenty-four patients in the
      observational cohort and 26 patients in the validation cohort exhibiting
      bacteriologically documented hospital-acquired pneumonia (HAP). INTERVENTIONS:
      Prospective data collection and multivariate analysis using the chi(2) automatic
      interaction and detection technique. RESULTS: In the observational cohort, 39
      antimicrobial-resistant bacteria were incriminated in 37 patients (30%).
      Multivariate analysis identified four independent variables allowing a binary
      stratification of risk. According to the presence or absence of prior
      antimicrobial treatment, neurologic disturbances on ICU admission, aspiration on
      ICU admission, and time elapsed between ICU admission and the onset of pneumonia,
      we were able to identify and separate patients at high, low, or even no risk for
      acquiring AR-HAP. In the validation cohort, nine antimicrobial-resistant bacteria
      were incriminated in nine patients (34.6%). In this cohort, the algorithm
      performed well allowing the identification of null risk categories: the absence
      of prior antimicrobial treatment, the presence of prior antimicrobial treatment
      with neurologic disturbances on ICU admission and an early-onset pneumonia, and
      the presence of prior antimicrobial treatment without neurologic disturbances but
      with aspiration on ICU admission were always associated with antimicrobial
      susceptible HAP. CONCLUSION: We developed and tested a binary algorithm allowing
      the identification of patients at low risk for acquiring AR-HAP. An antibiotic
      strategy including an initial antimicrobial treatment guided by such an
      algorithm, followed, if possible, by a de-escalation when antimicrobial data are
      available, could increase the administration of adequate initial antimicrobial
      treatment and help prevent the emergence of antibiotic resistance in the ICU.

PMID- 12796187
TI  - C-reactive protein levels correlate with mortality and organ failure in
      critically ill patients.
AB  - STUDY OBJECTIVES: C-reactive protein (CRP) is an acute-phase protein, the blood
      levels of which increase rapidly in response to infection, trauma, ischemia,
      burns, and other inflammatory conditions. Although used frequently in the ICU as
      a sepsis marker, the relation of CRP levels to organ damage is not well known.
      This study assessed the association between early serum CRP concentrations and
      the development of organ failure and mortality in ICU patients. DESIGN: A
      prospective cohort study. SETTING: A 31-bed ICU in a university hospital.
      PATIENTS: All 313 patients admitted to the ICU during the 4-month study period.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with high CRP levels at
      ICU admission had more severe organ dysfunction (higher sequential organ failure
      assessment scores, days of renal extracorporeal support therapy), longer ICU
      stays, and higher mortality rates than patients with normal ICU admission CRP
      levels. CRP concentrations were correlated with the presence and number of organ
      failures. ICU admission serum CRP levels > 10 mg/dL were associated with a
      significantly higher incidence of respiratory (65% vs 28.8%, p < 0.05), renal
      (16.6% vs 3.6%, p < 0.05), and coagulation (6.4% vs 0.9%, p < 0.05) failures, and
      with higher mortality rates (36% vs 21%, p < 0.05) than CRP levels < 1 mg/dL. In
      patients with CRP concentrations > 10 mg/dL on ICU admission, a decrease in CRP
      level after 48 h was associated with a mortality rate of 15.4%, while an
      increased CRP level was associated with a mortality rate of 60.9% (relative risk,
      0.25; 95% confidence interval, 0.07 to 0.91; p < 0.05). CONCLUSIONS: In a
      heterogeneous ICU population, elevated concentrations of serum CRP on ICU
      admission are correlated with an increased risk of organ failure and death.
      Moreover, persistently high CRP concentrations are associated with a poor
      outcome. Serial measurements may be helpful to identify those patients who
      require more aggressive interventions to prevent complications.

PMID- 12796188
TI  - Dead space ventilation in critically ill children with lung injury.
AB  - STUDY OBJECTIVE: In children with acute lung injury, there is an increase in
      minute ventilation (E) and inefficient gas exchange due to a high level of
      physiologic dead space ventilation (VD/VT). Mechanical ventilation with positive
      end-expiratory pressure, when used in critically ill patients to correct
      hypoxemia, may contribute to increased VD/VT. The purpose of this study was to
      measure metabolic parameters and VD/VT in critically ill children. DESIGN: A
      cross-sectional study. SETTING: Pediatric ICU of a university hospital. PATIENTS:
      A total of 45 mechanically intubated children (mean age, 5.5 years).
      INTERVENTIONS: Indirect calorimetry was used to measure metabolic parameters.
      VD/VT parameters were calculated using the modified Bohr-Enghoff equation. ARDS
      was defined based on criteria by The American-European Consensus Conference.
      MEASUREMENTS AND RESULTS: The group mean (+/- SD) ventilatory equivalent for
      oxygen (VeqO(2)) and ventilatory equivalent for carbon dioxide (VeqCO(2)) were
      2.9 +/- 1 and 3.3 +/- 1 L per 100 mL, respectively. The group mean VD/VT was 0.48
      +/- 0.2. When compared to non-ARDS patients (33 patients), the patients with ARDS
      (12 patients) had a significantly higher VeqO(2) (3.3 +/- 1 vs 2.8 +/- 1 L per
      100 mL, respectively; p < 0.05), a significantly higher VeqCO(2) (3.7 +/- 1 L/100
      vs 3.1 +/- 1 L per 100 mL, respectively; p < 0.05), and a significantly higher
      VD/VT (0.62 +/- 0.14 vs 0.43 +/- 0.15, respectively; p < 0.0005). CONCLUSIONS:
      Critically ill children with ARDS have increased VD/VT. Increased VD/VT was the
      main cause of the excess of E demand in these patients. Increased metabolic
      demands, as shown by the VeqO(2), VeqCO(2), and ventilatory support, are the
      major determinants of E requirements in children with ARDS.

PMID- 12796189
TI  - Short-term noninvasive pressure support ventilation prevents ICU admittance in
      patients with acute cardiogenic pulmonary edema.
AB  - STUDY OBJECTIVES: Noninvasive ventilation, although effective as treatment for
      patients with acute cardiogenic pulmonary edema when prolonged for hours, is of
      limited use in the emergency department (ED). The aim of the study was to
      determine whether a short attempt at noninvasive pressure support ventilation
      avoids ICU admittance and to identify lack of response prediction variables.
      DESIGN: Prospective inception cohort study. SETTING: ED of a university hospital.
      PATIENTS: Fifty-eight consecutive patients with cardiogenic pulmonary edema who
      had been unresponsive to medical treatment and were admitted between January 1999
      and December 2000. INTERVENTIONS: Pressure support ventilation was instituted
      through a full-face mask until the resolution of respiratory failure. A 15-min
      "weaning test" was performed to evaluate clinical stability. Responder patients
      were transferred to a medical ward. Nonresponding patients were intubated and
      were admitted to the ICU. MAIN OUTCOME MEASURES: The included optimal length of
      intervention, the avoidance of ICU admittance, the incidence of myocardial
      infarction, and predictive lack of response criteria. RESULTS: Patients completed
      the trial (mean [+/- SD] duration, 96 +/- 40 min). None of the responders (43
      patients; 74%) was subsequently ventilated or was admitted to the ICU. Two new
      episodes of myocardial infarction were observed. Thirteen of 58 patients died. A
      mean arterial pressure of < 95 mm Hg (odds ratio [OR], 10.6; 95% confidence
      interval [CI], 1.8 to 60.8; p < 0.01) and COPD (OR, 9.4; 95% CI, 1.6 to 54.0; p <
      0.05) at baseline predicted the lack of response to noninvasive ventilation.
      CONCLUSIONS: A short attempt at noninvasive ventilation is effective in
      preventing invasive assistance. A 15-min weaning test can identify patients who
      will not need further invasive ventilatory support. COPD and hypotension at
      baseline are negative predictive criteria.

PMID- 12796190
TI  - Evaluation of a practice guideline for noninvasive positive-pressure ventilation
      for acute respiratory failure.
AB  - OBJECTIVES: Clinical practice guidelines have been devised to change practitioner
      performance and to improve the process and outcomes of care. The objective of
      this study was to determine whether adherence to a practice guideline on
      noninvasive positive-pressure ventilation (NPPV) for the treatment of patients
      with acute respiratory failure (ARF) would change clinician behavior and resource
      utilization, and improve NPPV utilization and patient outcomes. DESIGN: Using a
      multidisciplinary team, we developed, implemented, and evaluated an NPPV practice
      guideline for ARF. Before and after guideline implementation, we recorded the
      incidence of endotracheal intubation (ETI) and mortality. Secondary outcomes were
      technological settings (ie, NPPV settings and duration) and NPPV administration
      (ie, cardiopulmonary monitoring, transfer to and time spent in the ICU, and
      pulmonary consultation). PARTICIPANTS: We enrolled 189 patients, 91 in the
      preguideline phase and 98 in the postguideline phase. Patients were similar in
      the both phases with respect to diagnoses at hospital admission and severity of
      illness. RESULTS: Of patients receiving NPPV for ARF, 67.3% fulfilled the
      guideline eligibility criteria in the postguideline phase compared to 62.6% in
      the preguideline phase (p = 0.543). Compared to the preguideline phase, more
      patients in the postguideline phase were transferred to the ICU (14.7% vs 33.7%,
      respectively; p = 0.003), spent more time in the ICU (30.9% vs 62.4%,
      respectively; p < 0.0001), and had consultation by a pulmonary physician (28.4%
      vs 49.0%, respectively; p = 0.004). There were no changes in technological
      settings. Guideline implementation was associated with improved cardiopulmonary
      monitoring. Nursing and respiratory therapist flow sheets were well-utilized
      during the guideline phase. There were no differences in ETI rates and mortality
      rates before and after guideline implementation. CONCLUSION: In this before-after
      study, we found that a multidisciplinary guideline for the use of NPPV for the
      treatment of patients with ARF was associated with changes in the process of
      care, with greater NPPV utilization in the ICU, and with increased pulmonary
      consultation, without any significant changes in the outcomes of care (ie, ETI
      and mortality rates).

PMID- 12796191
TI  - T helper type 2 cytokine receptors and associated transcription factors GATA-3, c
      MAF, and signal transducer and activator of transcription factor-6 in induced
      sputum of atopic asthmatic patients.
AB  - BACKGROUND: It is well-known that the expression of T helper (Th) type 2
      cytokines such as interleukin (IL)-4 and IL-5, and their receptors, is up
      regulated within the airways of allergic asthmatic patients. Furthermore, higher
      numbers of cells producing GATA-3, c-MAF, and signal transducer and activator of
      transcription factor (STAT)-6, which are transcription factors (TFs) that are
      implicated in the regulation and signaling of the Th2 cytokines, have been
      observed in bronchial biopsy specimens from asthmatic patients but not in those
      of healthy control subjects. METHODS: We examined whether these mediators also
      can be detected in induced sputum. Immunoreactivity for IL-4Ralpha, IL-5Ralpha,
      GATA-3, c-MAF, and STAT-6 was investigated in samples of induced sputum from
      asthmatic patients (n = 8) and healthy control subjects (n = 8). RESULTS: Our
      results showed that the numbers of cells expressing IL-4 receptor alpha (Ralpha)
      and IL-5Ralpha were higher in samples from asthmatic patients compared to those
      of control subjects (p < 0.01). More cells exhibiting GATA-3, c-MAF, and STAT-6
      immunoreactivity also were found in asthmatic patients vs those in control
      subjects (p < 0.005). Furthermore, the expression of STAT-6 and IL-4Ralpha, GATA
      3 and IL-5Ralpha, and c-MAF with both IL-4Ralpha and IL-5Ralpha was correlated (p
      < 0.05). CONCLUSIONS: This study demonstrated that induced sputum provides
      sufficient sensitivity for examining the pathways of cytokine signaling, cytokine
      receptor signaling, and intracellular signaling. Furthermore, these data show
      correlations between the expression of Th2 cytokine receptors and associated TFs
      in the human lung, which has not been documented previously.

PMID- 12796192
TI  - Extra-fine particles improve lung delivery of inhaled steroids in infants: a
      study in an upper airway model.
AB  - BACKGROUND: The particles of a new hydrofluoroalkane-134a (HFA)-beclomethasone
      dipropionate (BDP) metered-dose inhaler (Qvar; 3M Pharmaceuticals; St. Paul, MN)
      are considerably smaller than those of chlorofluorocarbon (CFC)-BDP. This may
      improve lung deposition in infants who inhale nasally and have irregular
      breathing patterns and small airways. AIM: To compare the dose delivered to the
      lungs of HFA-BDP and CFC-BDP at different breathing patterns using an upper
      airway model of an infant. METHODS: An anatomically correct upper airway model of
      a 9-month-old child with an open nasal airway was connected to an impactor and
      breathing simulator. HFA-BDP, 100 microg, and CFC-BDP, 100 micro g, were
      delivered to the model through a detergent-coated, small-volume spacer. The total
      dose leaving the model (lung dose), its particle size distribution, and median
      mass aerodynamic diameter (MMAD) were assessed during simulated tidal breathing
      with tidal volumes (VTs) of 50 mL, 100 mL, and 200 mL, and 30 breaths/min. Dose
      was expressed as percentage of nominal dose. RESULTS: Lung doses for HFA-BDP were
      25.4%, 26.5%, and 30.7% compared with 6.8%, 4.8%, and 2.1% for CFC-BDP at VTs of
      50 mL, 100 mL, and 200 mL, respectively. The dose of particles < 2.1 microm to
      the lung for HFA-BDP was 23 to 28% compared with 0.6 to 0.8% for CFC-BDP. The
      lung dose of CFC-BDP mainly consisted of particles between 2.1 microm and 4.7
      microm. MMAD for HFA-BDP was 1.2 microm, and 2.6 to 3.3 microm for CFC-BDP
      depending on VT. The lung dose for CFC-BDP decreased significantly with
      increasing VT. HFA-BDP lung dose did not alter significantly with VT.
      CONCLUSIONS: In this infant model study, the use of HFA-BDP with a high dose of
      particles < 2.1 microm improves the dose delivered to the lungs substantially.
      Furthermore, the large proportion of extra-fine particles in HFA-BDP results in
      lung doses less dependent on breathing pattern compared with CFC-BDP.

PMID- 12796194
TI  - Preoperative evaluation of patients undergoing lung resection surgery.
AB  - Lung cancer continues to be the leading case of cancer deaths in the United
      States. In patients with resectable non-small cell lung cancer, surgical
      resection is the treatment of choice. An accurate preoperative general and
      pulmonary-specific evaluation is essential as postoperative complications and
      morbidity of lung resection surgery are significant. After confirming anatomic
      resectability, patients must undergo a thorough evaluation to determine their
      ability to withstand the surgery and the loss of the resected lung. The
      measurement of spirometric indexes (ie, FEV(1)) and diffusing capacity of the
      lung for carbon monoxide (DLCO) should be performed first. If FEV(1) and DLCO are
      > 60% of predicted, patients are at low risk for complications and can undergo
      pulmonary resection, including pneumonectomy, without further testing. However,
      if FEV(1) and DLCO are < 60% of predicted, further evaluation by means of a
      quantitative lung scan is required. If lung scan reveals a predicted
      postoperative (ppo) values for FEV(1) and DLCO of > 40%, the patient can undergo
      lung resection. If the ppo FEV(1) and ppo DLCO are < 40%, exercise testing is
      necessary. If this reveals a maximal oxygen uptake (O(2)max) of > 15 mL/kg,
      surgery can be undertaken. If the O(2)max is < 15 mL/kg, surgery is not an
      option. This review discusses the existing modalities for preoperative evaluation
      prior to lung resection surgery.

PMID- 12796193
TI  - Efficacy of a new intraaortic propeller pump vs the intraaortic balloon pump: an
      animal study.
AB  - OBJECTIVE: To compare the efficacy of a new intraaortic propeller pump (PP) to
      provide hemodynamic support to the intraaortic balloon pump (IABP) in an acute
      mitral regurgitation (MR) animal model. BACKGROUND: A new intraaortic PP (Reitan
      catheter pump; Jomed; Helsingborg, Sweden) recently has been introduced. The
      pump's aim is a reduction in afterload via a deployable propeller that is placed
      in the high descending aorta and can be set at rotational speeds of <or= 14,000
      revolutions per minute (rpm). METHODS: In nine calves, acute MR was created by
      placing a vena cava filter in the mitral valve. The PP was tested at 6,000,
      10,000, and 14,000 rpm and was compared to 1:1 IABP support. Cardiac output,
      coronary blood flow, carotid artery flow, ascending and abdominal aortic
      pressure, left atrial pressure, and LV pressure-volume loops were recorded.
      RESULTS: The PP caused an rpm-dependent reduction in the mean ascending aortic
      pressure reaching -10 mm Hg (p < 0.05) at 14,000 rpm. However, mean (+/- SD)
      cardiac output did not improve (2.6 +/- 0.7 to 2.5 +/- 1.1 L/min; p = not
      significant), and mean diastolic coronary flow and carotid flow (47 +/- 16 to 35
      +/- 15 centiliters/min, p < 0.05) were reduced. The IABP improved cardiac output,
      and carotid and diastolic coronary flow. CONCLUSIONS: In this acute MR animal
      model, the PP reduced afterload but left out positive effects on cardiac output,
      which resulted in reduced perfusion of the upper body and the coronary
      circulation. Therefore, the IABP gives better hemodynamic support than the new PP
      in calves with acute MR.

PMID- 12796195
TI  - Cardiac rehabilitation following percutaneous revascularization, heart
      transplant, heart valve surgery, and for chronic heart failure.
AB  - This review discusses the scientific and clinical evidence for cardiac
      rehabilitation in patients who have undergone percutaneous revascularization,
      heart transplant, and heart valve surgery, and in patients with chronic heart
      failure. Across these diagnoses, regardless of age, there is considerable benefit
      of cardiac rehabilitation and supervised exercise training for increasing
      functional capacity, favorably modifying disease-related risk factors, decreasing
      symptoms, detecting signs and symptoms of disease before they become serious
      complications, and improving quality of life. The available evidence for this
      component of cardiovascular disease management, albeit not perfect, still
      warrants its more widespread application.

PMID- 12796196
TI  - Telephone diagnosis of a strange voice.

PMID- 12796197
TI  - Detection of lung cancer with volatile markers in the breath.
AB  - STUDY OBJECTIVES: To evaluate volatile organic compounds (VOCs) in the breath as
      tumor markers in lung cancer. Alkanes and monomethylated alkanes are oxidative
      stress products that are excreted in the breath, the catabolism of which may be
      accelerated by polymorphic cytochrome p450-mixed oxidase enzymes that are induced
      in patients with lung cancer. DESIGN: Combined case-control and cross-sectional
      study. SETTING: Five academic pulmonary medicine services in the United States
      and the United Kingdom. PATIENTS AND PARTICIPANTS: One hundred seventy-eight
      bronchoscopy patients and 41 healthy volunteers. INTERVENTION: Breath samples
      were analyzed by gas chromatography and mass spectroscopy to determine alveolar
      gradients (ie, the abundance in breath minus the abundance in room air) of C4-C20
      alkanes and monomethylated alkanes. MEASUREMENTS: Patients with primary lung
      cancer (PLC) were compared to healthy volunteers, and a predictive model was
      constructed using forward stepwise discriminant analysis of the alveolar
      gradients. This model was cross-validated with a leave-one-out jackknife
      technique and was tested in two additional groups of patients who had not been
      used to develop the model (ie, bronchoscopy patients in whom cancer was not
      detected, and patients with metastatic lung cancer [MLC]). RESULTS: Eighty-seven
      of 178 patients had lung cancer (PLC, 67 patients; MLC, 15 patients;
      undetermined, 5 patients). A predictive model employing nine VOCs identified PLC
      with a sensitivity of 89.6% (60 of 67 patients) and a specificity of 82.9% (34 of
      41 patients). On cross-validation, the sensitivity was 85.1% (57 of 67 patients)
      and the specificity was 80.5% (33 of 41 patients). The stratification of patients
      by tobacco smoking status, histologic type of cancer, and TNM stage of cancer
      revealed no marked effects. In the two additional tests, the model predicted MLC
      with a sensitivity of 66.7% (10 of 15 patients), and it classified the cancer
      negative bronchoscopy patients with a specificity of 37.4% (34 of 91 patients).
      CONCLUSIONS: Compared to healthy volunteers, patients with PLC had abnormal
      breath test findings that were consistent with the accelerated catabolism of
      alkanes and monomethylated alkanes. A predictive model employing nine of these
      VOCs exhibited sufficient sensitivity and specificity to be considered as a
      screen for lung cancer in a high-risk population such as adult smokers.

PMID- 12796198
TI  - Occupational asthma due to persulfate salts: diagnosis and follow-up.
AB  - BACKGROUND: Persulfate salts have been identified as a cause of occupational
      asthma (OA). The aim of the present study was to describe the clinical
      characteristics, diagnostic testing results, and follow-up of eight patients with
      OA that was triggered by these chemical compounds. METHODS: Eight patients with
      OA due to exposure to persulfate salts were studied. Immunologic, lung function,
      and specific bronchial challenge tests (SBCTs) were performed in all patients.
      Once their condition had been diagnosed, the patients were seen every 1, 3, and 6
      months for a mean duration of 18 months. RESULTS: The mean time of exposure to
      persulfate salts up to diagnosis was 15 years (range, 3 to 27 years), and mean
      time that had elapsed between symptom onset and diagnosis was 38 months (range, 3
      to 120 months). Three patients were smokers, six patients presented with rhinitis
      prior to asthma in relation to persulfate exposure, and three presented with
      dermatitis. The results of total IgE tests were positive in six patients, and the
      results of skin-prick tests for detection of persulfate salts were positive in
      five of these patients. The results of a SBCT was positive in the seven patients
      in whom it was performed. Symptoms persisted in all but one patient and required
      medical treatment. CONCLUSIONS: The results suggest that the reliable diagnosis
      of OA due to persulfate salts must be based on the specific challenge test until
      further experience has been acquired. Despite avoiding exposure, patients
      continued with symptoms and required treatment for the control of symptoms.
      Finally, a dependent IgE mechanism appears to be implicated in the pathogenesis
      of OA due to exposure to persulfate salts.

PMID- 12796199
TI  - Does deficiency of arylsulfatase B have a role in cystic fibrosis?
AB  - Cystic fibrosis (CF) is associated with mutation and abnormal function of the
      cystic fibrosis transmembrane conductance regulator (CFTR) that affects cellular
      chloride transport. Clinically, CF of the lung is associated with excessive
      accumulation of secretions, including the sulfated glycosaminoglycans,
      chondroitin sulfate and dermatan sulfate (DS), both of which contain sulfated N
      acetylgalactosamine residues. The sulfatase enzymes, which are a highly conserved
      group of enzymes with high specificity for designated sulfate groups, include
      arylsulfatase B, a lysosomal enzyme. Arylsulfatase B, also known as N-acetyl
      galactosamine 4-sulfatase, can degrade DS and chondroitin-4 sulfate. Previously
      reported data demonstrated diminished activity of arylsulfatase B in lymphoid
      cell lines of patients with CF compared to normal control subjects. Frequent
      infections with Pseudomonas, a sulfatase-producing organism, occur in patients
      with CF, whereas infections with Mycobacterium tuberculosis, which lacks
      sulfatase activity, are infrequent. Additional investigation to determine if
      diminished function of arylsulfatase B is a consistent finding in cells of
      patients with CF may be informative, and may help to correlate the molecular,
      biochemical, and clinical characteristics of CF.

PMID- 12796200
TI  - A 63-year-old man with suspected lung cancer and acute renal failure.

PMID- 12796201
TI  - Transcatheter closure of traumatic ventricular septal defect: an alternative to
      surgery.
AB  - The incidence of ventricular septal defect (VSD) occurs in up to 4.5% of
      penetrating cardiac trauma. We report a patient with persistent VSD who underwent
      surgical repair with significant left-to-right shunt and signs of heart failure.
      We performed a successful transcatheter closure of the VSD with an Amplatzer
      septal occluder (AGA Medical Corporation; Golden Valley, MN).

PMID- 12796202
TI  - Relapsing acute respiratory failure induced by minocycline.
AB  - The antibiotic minocycline, which is used in the treatment of acne, has been
      associated with various pulmonary complications such as pulmonary lupus and
      hypersensitivity pneumonitis. We now report a particularly severe case of
      minocycline-related pulmonary toxicity that was characterized by a relapsing form
      of hypersensitivity eosinophilic pneumonia complicated by acute respiratory
      failure.

PMID- 12796203
TI  - Tracheal lobular capillary hemangioma: a rare cause of recurrent hemoptysis.
AB  - Lobular capillary hemangioma (LCH) is a polypoid form of capillary hemangioma
      occurring on the skin and mucosal surfaces. While LCH of the oral and nasal
      cavity is a well-known entity, tracheal localization is extremely rare. We
      present the case of a 72-year-old woman with recurrent hemoptysis due to a small
      tumor of the proximal trachea. By endoscopic removal of the tumor by flexible
      bronchoscopy, the diagnosis of LCH was made, and during the following year there
      was no recurrent hemoptysis. To our knowledge, this is the first case of
      histologically proven LCH of the trachea.

PMID- 12796204
TI  - Methotrexate-induced pulmonary lymphoma.
AB  - Methotrexate has proven to be effective in treating rheumatoid arthritis (RA),
      and is believed to be nononcogenic in the low weekly dose typically employed in
      the patients with RA. We report, however, a patient with RA in whom a rapidly
      enlarging diffuse large B-cell lymphoma developed in the left upper lung after
      weekly treatment with methotrexate for 5 years. The patient had a positive serum
      IgG for Epstein-Barr virus but a negative in situ hybridization of the resected
      specimen. Methotrexate therapy was discontinued, and the patient elected for
      clinical observation instead of chemotherapy or radiation therapy. There has been
      no clinically detectable recurrence of the lymphoproliferative disorder for 2
      years. We believe that methotrexate has an oncogenic potential even in low weekly
      dosing in a subset of patients with RA and latent Epstein-Barr virus infection.
      The strongest causal link is demonstrated by the persistent tumor remission after
      stopping treatment with methotrexate.

PMID- 12796205
TI  - Lung sonography in pulmonary embolism.

PMID- 12796207
TI  - Noninvasive ventilation is more than mask ventilation.

PMID- 12796206
TI  - Cyclooxygenase-2 inhibitors in aspirin-sensitive asthma.

PMID- 12796208
TI  - Modification of blood culture recommendations?

PMID- 12796209
TI  - Anaerobic blood cultures: useful in the ICU?

PMID- 12796210
TI  - Is mushroom workers' chronic cough the same as byssinosis and what should the
      occupational exposure limit be for endotoxin?

PMID- 12796211
TI  - Oximeter performance and diagnostic accuracy of sleep studies.

PMID- 12796212
TI  - Microdrainage via open technique in severe subcutaneous emphysema.

PMID- 12796213
TI  - Risk of bleeding associated with transbronchial lung biopsy.

PMID- 12796214
TI  - What is the effect of fingernail polish on pulse oximetry?

PMID- 12796217
TI  - Pinel delivering the insane.

PMID- 12796218
TI  - A meta-analysis of the efficacy of second-generation antipsychotics.
AB  - BACKGROUND: Consensus panel recommendations regarding choice of an antipsychotic
      agent for schizophrenia differ markedly, but most consider second-generation
      antipsychotics (SGAs) as a homogeneous group. It has been suggested that SGAs
      seem falsely more efficacious than first-generation antipsychotics (FGAs) as a
      result of reduced efficacy due to use of a high-dose comparator, haloperidol. We
      performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and
      FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and
      SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an
      FGA comparator. METHODS: Literature search of clinical trials between January
      1953 and May 2002 of patients with schizophrenia from electronic databases,
      reference lists, posters, the Food and Drug Administration, and other unpublished
      data. We included 124 randomized controlled trials with efficacy data on 10 SGAs
      vs FGAs and 18 studies of comparisons between SGAs. Two of us independently
      extracted the sample sizes, means, and standard deviation of the efficacy data.
      RESULTS: Using the Hedges-Olkin algorithm, the effect sizes of clozapine,
      amisulpride, risperidone, and olanzapine were 0.49, 0.29, 0.25, and 0.21 greater
      than those of FGAs, with P values of 2 x 10-8, 3 x 10-7, 2 x 10-12, and 3 x 10-9,
      respectively. The remaining 6 SGAs were not significantly different from FGAs,
      although zotepine was marginally different. No efficacy difference was detected
      among amisulpride, risperidone, and olanzapine. We found no evidence that the
      haloperidol dose (or all FGA comparators converted to haloperidol-equivalent
      doses) affected these results when we examined its effect by drug or in a 2-way
      analysis of variance model in which SGA effectiveness is entered as a second
      factor. CONCLUSION: Some SGAs are more efficacious than FGAs, and, therefore,
      SGAs are not a homogeneous group.

PMID- 12796219
TI  - Sex differences in the risk of schizophrenia: evidence from meta-analysis.
AB  - BACKGROUND: Sex differences in the risk of a particular disorder can yield
      important clues regarding its pathogenesis. The evidence for a sex difference in
      the risk of schizophrenia is inconclusive. The purpose of this study was to
      integrate results from the published literature and to provide a quantitative
      index of the male-female ratio for the incidence of schizophrenia. METHODS: The
      MEDLINE and PsychLIT databases were searched for English-language publications on
      "incidence and schizophrenia" that appeared during the period between January
      1980 and September 2001. Population-based incidence studies using standard
      clinical diagnostic criteria were included if they reported sex-specific
      incidence rates. Sex-specific incidence figures were extracted directly from each
      study. Categorical analyses were conducted on a subset of studies that met
      specific methodological criteria (to minimize criterion bias, hospital bias, and
      age bias). Study categorization and data extraction were performed independently
      by 2 of us (A. A. and J.-P.S.). RESULTS: Log risk ratio meta-analysis was
      conducted using a random-effects model. The incidence risk ratios for men to
      develop schizophrenia relative to women were 1.42 (95% confidence interval [CI],
      1.30-1.56) when all studies were included in the analysis (49 effect sizes), 1.31
      (95% CI, 1.13-1.51) when studies that minimized selection biases were analyzed
      separately (23 effect sizes), and 1.39 (95% CI, 1.15-1.68) when only high-quality
      studies were included (11 effect sizes). The sex difference was significantly
      smaller in studies with sample years before 1980 than those with sample years
      after 1980. No significant sex differences were reported in studies from
      developing countries. A final analysis, limited to studies with an age cutoff of
      64 years or older (16 effect sizes), yielded a mean risk ratio of 1.32 (95% CI,
      1.13-1.55). CONCLUSION: This meta-analysis provides evidence for a sex difference
      in the risk of developing schizophrenia, as reported in the published literature
      from the last 2 decades.

PMID- 12796220
TI  - Decreased serum levels of D-serine in patients with schizophrenia: evidence in
      support of the N-methyl-D-aspartate receptor hypofunction hypothesis of
      schizophrenia.
AB  - BACKGROUND: The hypofunction of the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptors has been implicated in the pathophysiology of schizophrenia.
      Several lines of evidence suggest that D-serine may function as an endogenous
      agonist of the glycine site of the NMDA receptor. The aim of this study was to
      examine whether serum levels of D- and L-serine in patients with schizophrenia
      are different from those of healthy controls. METHODS: Forty-two patients with
      schizophrenia and 42 age- and sex-matched healthy controls were enrolled in this
      study. Symptoms were assessed using the Brief Psychiatric Rating Scale. Serum
      levels of total serine and D- and L-serine were measured by high-performance
      liquid chromatography. RESULTS: Serum levels of D-serine in the patients with
      schizophrenia were significantly (z = -3.30, P =.001) lower than those of healthy
      controls. In contrast, serum levels of total (D and L) serine (z = -2.40, P =.02)
      and L-serine (z = -2.49, P =.01) in the schizophrenic patients were significantly
      higher than those of controls. In addition, the percentage of D-serine in the
      total serine in the schizophrenic patients was significantly (z = -4.78, P<.001)
      lower than that of controls, suggesting that the activity of serine racemase, an
      enzyme catalyzing the formation of D-serine from L-serine, may have been reduced
      in the schizophrenic patients. CONCLUSIONS: Reduced levels of D-serine may play a
      role in the pathophysiology of schizophrenia, and serum D- and L-serine levels
      might provide a measurable biological marker for schizophrenia.

PMID- 12796221
TI  - Olfaction and social drive in schizophrenia.
AB  - BACKGROUND: The neurobiology of social dysfunction in schizophrenia is unknown,
      but smell identification deficits (SIDs) exist in schizophrenia, and olfaction is
      related to social affiliation in other mammals. The SIDs have been linked with
      negative symptoms and the deficit syndrome, but any specificity of SIDs for
      social dysfunction is unstudied. Low intelligence might explain this
      relationship, if it is associated with both negative symptoms and SIDs. We
      examined whether SIDs in schizophrenia were related broadly to negative symptoms,
      as are a number of other neuropsychological measures, or whether they might show
      a more specific relationship with social drive. METHODS: Smell Identification
      Test scores, Wechsler Adult Intelligence Scale-Revised IQ, symptomatology
      assessed with the Positive and Negative Syndrome Scale, and the deficit syndrome
      were determined in 70 patients with DSM-IV schizophrenia. RESULTS: The SIDs were
      related to negative symptoms and the deficit syndrome, but the association of
      SIDs with diminished social drive explained both relationships. Smell
      identification was also related to Wechsler Adult Intelligence Scale-Revised IQ,
      but intelligence was independent of the relationship of SID and social drive. The
      worse Smell Identification Test scores in male patients were attributable to a
      greater preponderance of men with the deficit syndrome. CONCLUSIONS: These
      analyses demonstrated independent relationships of Smell Identification Test
      scores to social drive and intelligence that together accounted for almost 50% of
      the variance in Smell Identification Test scores. There may be common neural
      substrates for the low social drive and SIDs in schizophrenia.

PMID- 12796222
TI  - Progressive structural brain abnormalities and their relationship to clinical
      outcome: a longitudinal magnetic resonance imaging study early in schizophrenia.
AB  - BACKGROUND: Many studies have shown that structural brain abnormalities in
      schizophrenia are already present by the time of index evaluation of first
      episode patients. However, whether these abnormalities progressively worsen
      during the subsequent course of the disorder remains unresolved. METHODS: To
      study the longitudinal progression of structural brain abnormalities, high
      resolution multispectral magnetic resonance images obtained on 73 recent-onset
      schizophrenic patients and 23 controls were analyzed using state-of-the-art, well
      validated, and highly reliable neuroimaging tools. The mean duration between
      initial and follow-up MRIs was 3 years. Repeated-measures analysis of covariance
      was carried out to determine (1) whether brain volume changes differed between
      patients and controls and (2) the significance of regional brain changes on
      functional outcome in schizophrenia. RESULTS: We found accelerated enlargement in
      cortical sulcal cerebrospinal fluid spaces early in the course of schizophrenia.
      Instead of the usual trajectory of volume enlargement, patients showed
      progressive reduction in frontal lobe white matter volume. A reciprocal increase
      in frontal lobe cerebrospinal fluid volume also occurred at a more rapid rate in
      patients than in controls. In keeping with most of our a priori hypotheses,
      patients with poor outcome had greater lateral ventricular enlargement over time
      than patients with good outcome. Progressive decrement in frontal lobe white
      matter volume and enlargement in frontal lobe cerebrospinal fluid volume were
      associated with greater negative symptom severity. Reductions in frontal lobe
      gray and white matter volumes correlated with poorer executive functioning.
      CONCLUSIONS: There are ongoing changes in the brains of schizophrenic patients
      during the initial years after diagnosis despite ongoing antipsychotic drug
      treatment. These progressive changes seem to be most evident in the frontal lobes
      and to correlate with functional impairment. Disruptions in neurodevelopment or
      neural plasticity may act alone or in combination to bring about these
      progressive brain deficits in schizophrenia.

PMID- 12796223
TI  - A functional magnetic resonance imaging study of bipolar disorder: state- and
      trait-related dysfunction in ventral prefrontal cortices.
AB  - BACKGROUND: Abnormalities in prefrontal and anterior cingulate cortices are
      implicated in disturbances of attention, cognition, and impulse regulation in
      bipolar disorder. Acute episodes have been associated with dysfunction in these
      brain regions, and more enduring trait-related dysfunction has been implicated by
      volumetric and cellular abnormalities in these regions. The relative
      contributions of prefrontal regions to state and trait disturbances in bipolar
      disorder, however, have not been defined. We sought to characterize state- and
      trait-related functional impairment in frontal systems in bipolar disorder.
      METHODS: Thirty-six individuals with bipolar disorder I (11 with elevated, 10
      with depressed, and 15 with euthymic mood states) and 20 healthy control subjects
      matched for handedness and sex participated in an event-related functional
      magnetic resonance imaging study of the color-word Stroop to determine mean
      percentage of regional task-related signal change. RESULTS: Signal increased
      during the Stroop task similarly across diagnostic groups in a distribution that
      included dorsal anterior cingulate and prefrontal cortices, consistent with
      previously reported activations in this task. Signal changes associated with
      specific mood states in bipolar disorder were detected in ventral prefrontal
      cortex, with a blunted increase in signal on the right side in the elevated mood
      group (P =.005) and an exaggerated increase in signal on the left side in the
      depressed group (P =.02) compared with the euthymic group. Patients (vs healthy
      controls) demonstrated blunted activation in a spatially distinct, rostral region
      of left ventral prefrontal cortex that was independent of mood state (P<.005).
      CONCLUSIONS: Bipolar disorder is associated with a trait abnormality in left
      ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be
      associated with specific acute mood states. The hemispheric laterality of the
      abnormality and the directions of signal change may relate to the valence of the
      mood episode.

PMID- 12796224
TI  - Occurrence and course of suicidality during short-term treatment of late-life
      depression.
AB  - BACKGROUND: Elderly persons (> or =65 years) have the highest rate of suicide;
      still, little is known about the occurrence, course, and responsivity of suicidal
      ideation during treatment of depression in late life and how suicidality affects
      treatment response. METHODS: This study was undertaken to determine (1) how
      suicidal ideation changes during short-term depression treatment and (2) whether
      treatment response differs among 3 groups of patients based on their levels of
      suicidality at baseline and during treatment (those with a recent suicide attempt
      or current suicidal ideation [high-risk group; n = 46], those with recurrent
      thoughts of death [moderate-risk group; n = 143], or those with no suicide
      attempt, suicidal ideation, or thoughts of death [low-risk group; n = 206]). This
      is a secondary analysis of pooled data from 3 treatment studies of late-life
      major depression. Participants were 395 elderly persons with a current major
      depressive episode, treated as inpatients or outpatients under protocolized
      conditions with paroxetine hydrochloride or nortriptyline hydrochloride, with or
      without interpersonal psychotherapy. Changes in suicidal ideation over time, rate
      of responses, and time to response in each group were compared. RESULTS: Suicidal
      ideation decreased rapidly early in the course of treatment, with more gradual
      change thereafter. At the beginning of treatment, 77.5% of the patients reported
      suicidal ideation, thoughts of death, or feelings that life is empty. After 12
      weeks of treatment, suicidal ideation had resolved in all treated patients; 4.6%
      still reported thoughts of death. However, 6-week (P =.001) and 12-week (P =.02)
      rates of response were significantly lower in high-risk patients than in low- and
      moderate-risk patients. High- and moderate-risk patients needed a significantly
      (P<.001) longer time to respond than low-risk patients (median time to response,
      6 and 5 vs 3 weeks). CONCLUSIONS: While suicidal ideation resolves rapidly, the
      resolution of thoughts about death is more gradual. Suicidal elderly persons with
      depression require special attention during depression treatment because they
      have a lower response rate and need a longer time to respond.

PMID- 12796225
TI  - Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety
      and depression: the Hordaland Homocysteine Study.
AB  - BACKGROUND: An association between depression and folate status has been
      demonstrated in clinical studies, whereas data are sparse on the relationship
      between depression and other components of 1-carbon metabolism such as vitamin
      B12, homocysteine, and the methylenetetrahydrofolate reductase 677C-->T
      polymorphism. The relationship between anxiety and these components is less well
      known. This study examined the associations between folate, total homocysteine,
      vitamin B12, and the methylenetetrahydrofolate reductase 677C-->T polymorphism,
      and anxiety and depression in a large population-based study. METHODS: Anxiety
      and depression, measured by the Hospital Anxiety and Depression Scale, were
      assessed in 5948 subjects aged 46 to 49 years (mean, 47.4 years) and 70 to 74
      years (mean, 71.9 years) from the Hordaland Homocysteine Study cohort. By means
      of logistic regression models, anxiety and depression scores were examined in
      relation to the factors listed above. RESULTS: Overall, hyperhomocysteinemia
      (plasma total homocysteine level > or =15.0 micro mol/L [> or =2.02 mg/dL]) (odds
      ratio, 1.90; 95% confidence interval, 1.11-3.25) and T/T
      methylenetetrahydrofolate reductase genotype (odds ratio, 1.69; 95% confidence
      interval, 1.09-2.62), but not low plasma folate or vitamin B12 levels, were
      significantly related to depression without comorbid anxiety disorder. Plasma
      folate level was inversely associated with depression only in the subgroup of
      middle-aged women. None of the investigated parameters showed a significant
      relationship to anxiety. CONCLUSION: Our results provide further evidence of a
      role of impaired 1-carbon metabolism in depression.

PMID- 12796226
TI  - Depression and other psychological risks following myocardial infarction.
AB  - BACKGROUND: There is consistent evidence that depression symptoms predict long
      term mortality following a myocardial infarction, and recent results show a dose
      related gradient. The importance of other psychological variables remains
      unclear. METHODS: This study examines the relative importance of depression,
      anxiety, anger, and social support in predicting 5-year cardiac-related mortality
      following a myocardial infarction and assesses the role of any common underlying
      dimensions. The design of this cohort analytic study involves self-reports (Beck
      Depression Inventory, state scale of the State-Trait Anxiety Inventory, 20-item
      version of the General Health Questionnaire, Modified Somatic Perception
      Questionnaire, Anger Expression Scale, Perceived Social Support Scale, number of
      close friends and relatives, and visual analog scales of anger and stress). The
      study was conducted in 10 Montreal-area hospitals. The patients included 896
      persons who experienced a myocardial infarction, aged 24 to 88 years (232 were
      women), followed up for 5 years using Medicare records; baseline data were
      complete for 95.0% of the patients. The intervention was usual care, and the main
      outcome measure was 5-year cardiac-related mortality. RESULTS: The Beck
      Depression Inventory (P<.001), the State-Trait Anxiety Inventory (P =.04), and
      the 20-item version of the General Health Questionnaire (P =.048) were related to
      outcome), but only depression remained significant after adjustment for cardiac
      disease severity (hazards ratio per SD, 1.46; 95% confidence interval, 1.18-1.79)
      (P<.001). Exploratory factor analysis revealed 3 underlying factors: negative
      affectivity, overt anger, and social support. There was also a covariate-adjusted
      trend between negative affectivity scores and outcome (P =.08). Furthermore,
      residual depression scores (P =.001) and negative affectivity scores (P =.05)
      were linked to cardiac-related mortality after adjustment for each other and
      cardiac covariates. CONCLUSIONS: Negative affectivity and some unique aspect of
      depression predict long-term cardiac-related mortality following a myocardial
      infarction independently of each other and cardiac disease severity. Additional
      research is needed to characterize the mechanisms involved.

PMID- 12796227
TI  - Diagnostic patterns in Latino, African American, and European American
      psychiatric patients.
AB  - BACKGROUND: The purpose of this study was to examine whether Latino patients
      presenting for behavioral health treatment showed major systematic differences in
      presenting symptoms, clinical severity, and psychiatric diagnosis compared with
      European American and African American patients. Documenting such differences
      should have important implications for evidence-based clinical practice. METHODS:
      Data were drawn from a large behavioral health service delivery system in New
      Jersey, and included administrative data, clinical diagnosis, a clinician-rated
      global level of functioning, and a self-reported symptoms and functioning scale.
      The study involved a clinical sample of all new admissions into the system
      between January 1, 2000, and August 31, 2001. To examine the main effects of
      ethnicity, in the context of other independent variables, logistic regression was
      performed for each of 3 dependent binary variables: presence or absence of major
      depression, a schizophrenia spectrum disorder, and bipolar disorder. RESULTS:
      Consistent with previous studies, we found that African Americans were diagnosed
      as having a disorder in the schizophrenic disorders spectrum more frequently than
      did Latinos and European Americans (odds ratio, 1.80; 95% confidence interval,
      1.62-2.00). Latinos were disproportionately diagnosed as having major depression,
      despite the fact that significantly higher levels of psychotic symptoms were self
      reported by Latinos (odds ratio, 1.74; 95% confidence interval, 1.56-1.93).
      CONCLUSIONS: Latinos in this study were more likely to be clinically diagnosed as
      having major depression than were other ethnic groups. Further research is needed
      to determine the reasons for these systematic differences. Possible explanations
      include (1) self-selection, (2) culturally determined expression of symptoms, (3)
      difficulties in the accurate application of DSM-IV diagnostic criteria to
      Latinos, (4) bias related to lack of clinicians' cultural competence, and (5)
      imprecision inherent in the use of unstructured interviews, possibly combined
      with clinician bias. Additional research is required to determine the
      generalizability, accuracy, and applicability of these findings and their
      possible mechanisms.

PMID- 12796228
TI  - Diagnostic testing of the febrile neonate: it is time to collaborate.

PMID- 12796229
TI  - Beyond the complete blood cell count and C-reactive protein: a systematic review
      of modern diagnostic tests for neonatal sepsis.
AB  - OBJECTIVE: To systematically review the accuracy of modern laboratory tests for
      the diagnosis of serious bacterial infection in newborns. METHODS: The MEDLINE,
      EMBASE, and Cochrane Library databases were searched using the keywords newborn,
      infection, sepsis, and diagnosis. We included studies published from 1995 through
      2001 that included infants younger than 90 days with proven bacterial growth in a
      sample from a sterile site. Whenever possible, relevant data were extracted to
      calculate likelihood ratios (LRs) for whether each test can diagnose a serious
      bacterial infection. Two independent reviewers selected and reviewed the articles
      (interobserver agreement, kappa = 0.80). All disagreements were resolved by
      consensus. RESULTS: Of the 137 citations we retrieved, 37 articles met the
      inclusion criteria; 17 studies, evaluating 11 different tests, met the highest
      methodological criteria. The most commonly evaluated test was interleukin 6 (IL
      6) level (n = 7 studies). The remaining tests were each evaluated in no more than
      3 studies. Positive LRs ranged from 1.5 to infinity. Six individual tests
      examined in 8 studies had LRs of more than 10 (range, 12.5- infinity ). Combined
      tests also had a wide range of LRs (3.4-9.9). All studies were performed in
      single medical centers and had small sample sizes, making recommendations
      according to gestational age criteria difficult. CONCLUSIONS: We found few
      methodologically rigorous studies of the accuracy of laboratory tests for the
      diagnosis of bacterial infection in newborns; in a significant proportion of
      studies, the accuracy of the tests could not be independently determined because
      of a lack of adequate data. There was marked heterogeneity in sample selection
      and cutoff levels for diagnosis of neonatal sepsis. A few tests showed promising
      accuracy, but there are insufficient data to support their confident use as
      clinical tools.

PMID- 12796230
TI  - Use of nicotine replacement therapy in adolescent smokers and nonsmokers.
AB  - BACKGROUND: Assessing whether and how adolescents use nicotine replacement
      therapy (NRT) will be important given recent recommendations to make NRT more
      accessible by lowering its price, increasing its distribution, and advising
      health care professionals to suggest its use for smoking cessation. OBJECTIVES:
      To report the prevalence, ease of access, and reasons for NRT use and describe
      inappropriate use in adolescent smokers and nonsmokers. DESIGN: Cross-sectional
      survey of 4078 high school students during the school term of 1998. SETTING: City
      schools in Memphis, Tenn. MAIN OUTCOME MEASURES: Community-based self-reported
      prevalence of NRT use and characteristics of those using NRT. RESULTS:
      Approximately 5% of adolescents reported trying or using nicotine gum or patches.
      Females were less likely than males and African Americans were less likely than
      others to use NRT. For African American smokers, NRT use was highest at lower
      smoking levels, while other smokers showed the opposite pattern. Almost 40% of
      former smokers reported using NRT to try to quit smoking; however, 75% of current
      smokers endorsed using NRT for reasons other than trying to quit smoking. Other
      inappropriate use of NRT was reported; 18% of NRT users reported themselves as
      never smokers. More than 50% of students reported that it would be easy for them
      to get NRT. CONCLUSIONS: Nicotine replacement therapy is used by adolescent
      smokers and nonsmokers, is easily accessible, and is used for reasons other than
      trying to quit smoking. Efforts are needed to discourage NRT use in nonsmoking
      youth and to encourage appropriate use of NRT in young smokers to maximize its
      potential for successful cessation.

PMID- 12796232
TI  - Characteristics of African American teenage smokers who request cessation
      treatment: implications for addressing health disparities.
AB  - BACKGROUND: Ethnoracial disparities in both tobacco-related mortality and
      treatment outcome for smoking cessation have been reported among adults, but
      there is a dearth of information on ethnoracial differences among adolescent
      smokers. OBJECTIVE: To compare smoking-related characteristics in African
      American and non-African American teenaged applicants for a smoking cessation
      trial. PARTICIPANTS, DESIGN, AND SETTING: Four hundred thirty-two teenaged
      smokers (mean [SD] age, 15.6 [1.5] years; 61.8%, female; 31.9%, African American)
      responded via telephone to various media advertisements. Self-reported
      sociodemographic, smoking-related, and clinical data were obtained to determine
      preeligibility for trial participation. MAIN OUTCOME MEASURES: The number of
      cigarettes smoked per day, Fagerstrom Test for Nicotine Dependence (FTND) score,
      motivation to quit, self-reported health problems, and medication use. RESULTS:
      Compared with non-African Americans, African Americans had lower FTND scores
      (mean [SD] score, 5.31 [2.24] vs 6.18 [2.18]; P<.01), and smoked fewer cigarettes
      per day (mean [SD] number of cigarettes, 12.6 [8.3] vs 15.4 [7.5] cigarettes/d;
      P<.04). The FTND scores were similar in both groups when adjusted for the number
      of cigarettes smoked per day. African American and non-African American teenagers
      reported similar motivation to quit (mean [SD] score, 8.64 [1.68] vs 8.53 [1.59],
      respectively). No difference was found in frequency of physical health problems
      (eg, asthma), diagnosed psychiatric conditions, or prescribed psychiatric
      medication although fewer African American teenaged smokers took medication for
      physical problems (21.2% vs 36.7%). CONCLUSIONS: Cessation treatment
      interventions designed for African American youths should include lower FTND
      defined levels, or the use of other instruments that do not focus on the number
      of cigarettes smoked per day. Our findings also highlight the importance of
      ethnocultural issues in treatment research that aims to address health
      disparities.

PMID- 12796231
TI  - Improving participation in Chlamydia screening programs: perspectives of high
      risk youth.
AB  - BACKGROUND: Many young people at highest risk for chlamydial infection do not use
      chlamydia screening services. OBJECTIVES: To describe young people's beliefs and
      opinions about obstacles to and motivators for obtaining testing and to provide
      recommendations for how to improve youth participation in chlamydia screening
      programs. METHODS: Eight focus group interviews (4 male and 4 female groups) were
      conducted with young people using a semistructured interview guide. Thirty-two
      male and 23 female volunteers (mean age, 18.2 years; age range, 15-24 years) were
      recruited from Job Corps and Department of Youth Services sites. The main outcome
      measure was categorization of textual data using content analysis techniques.
      Data were coded by 2 investigators into categories of responses based on research
      questions and spontaneously offered comments. Satisfactory intercoder agreement
      was achieved. RESULTS: Participants described many obstacles to testing,
      including concern that someone will know they were tested or tested positive,
      fear about discovering they have a sexually transmitted disease, and fear of
      acquired immunodeficiency syndrome. Many participants were unsure what physical
      effects chlamydia produced or thought it was possible to die of a chlamydial
      infection. Participants recommended providing more information about the effects
      of chlamydia, availability of urine testing, and ease of treatment to motivate
      more young people to seek testing. They also emphasized the need to make sexually
      transmitted disease screening services more private and confidential. There was
      an overwhelming interest in using a home Chlamydia test (much like a home
      pregnancy test) if one were available. CONCLUSIONS: To increase youth
      participation in screening programs, it will be necessary to address their
      concerns, dispel misconceptions, and provide more information about chlamydia. A
      home Chlamydia test might be one way to increase screening.

PMID- 12796233
TI  - Health consequences for children with undiagnosed asthma-like symptoms.
AB  - BACKGROUND: A growing body of evidence indicates that there are a substantial
      number of children who report asthma-like symptoms and are not diagnosed with
      asthma. However, there is little information on the health consequences of asthma
      like symptoms for children with these symptoms and no asthma diagnosis.
      OBJECTIVE: To assess the prevalence and health consequences (school absences,
      sleep disturbances, activity limitations, physician visits, emergency department
      visits, and hospitalizations) of asthma-like symptoms among children with and
      without physician diagnosis. STUDY DESIGN: We surveyed 122 829 children aged 12
      to 14 years in 499 North Carolina public middle schools. A standardized
      questionnaire (International Study of Asthma and Allergies in Childhood [ISAAC])
      containing video scenes of adolescents experiencing asthma-like symptoms was
      adapted to include questions on health consequences. RESULTS: Seventeen percent
      (n = 21 184) reported current asthma-like symptoms with no diagnosis of asthma
      (during the last 12 months.) Eleven percent (n = 13 619) of the children reported
      physician-diagnosed asthma with current asthma-like symptoms. Of the children
      with asthma-like symptoms and no diagnosis of asthma, 20% missed a half day or
      more of school per month because of wheeze, 25% had limited activities because of
      wheeze once or more per month, and 32% had sleep disturbances because of wheeze
      in the last 4 weeks. Seven percent of children with current asthma-like symptoms
      but no diagnosis reported 1 or more emergency department visits for asthma-like
      symptoms, and 5% reported wheeze-related hospitalizations in the last year. Of
      children with physician-diagnosed asthma, almost half (47%) reported missing a
      half day or more of school in the last month. Thirty percent of physician
      diagnosed children reported 1 or more emergency department visits in the last
      year for asthma-like symptoms. CONCLUSIONS: The health consequences of asthma
      like symptoms in children with no diagnosis are substantial; these children are
      essentially untreated. Better detection of this disease group by the medical
      community has the potential to improve health consequences for these children.

PMID- 12796234
TI  - Risk of mental retardation among children born with birth defects.
AB  - BACKGROUND: A paucity of epidemiologic research exists concerning the co
      occurrence of birth defects and mental retardation (MR). Study of this co
      occurrence may yield important clues about the causes of both. OBJECTIVE: To
      examine the co-occurrence of birth defects and MR, taking into consideration the
      type of birth defect, level of MR, co-occurrence of MR with other developmental
      disabilities, and individual and maternal factors. DESIGN: A retrospective cohort
      study of infants born in the California Central Valley with and without a
      structural birth defect by 1 year of age, and with or without MR by 7 to 9 years
      of age. SETTING AND PARTICIPANTS: One-year survivors (N = 119 556) born in
      nonmilitary hospitals in 8 California counties between January 1, 1992, and
      December 31, 1993, for whom information about birth defects was recorded within
      the first year of life. MAIN OUTCOME MEASURE: Diagnosis of MR by age 7 years
      considered as being mild or severe and as occurring without other developmental
      disabilities (isolated MR) or as occurring with other developmental disabilities,
      including cerebral palsy, epilepsy, or a pervasive developmental disorder.
      RESULTS: Children with birth defects were nearly 27 times more likely to have MR
      by 7 years of age compared with children without a diagnosed birth defect
      regardless of type of defect (prevalence ratio, 26.8; 95% confidence interval,
      22.7-31.7). Among those with birth defects, children with Down syndrome
      (prevalence ratio, 211.7; 95% confidence interval, 171.3-261.5) and children with
      sex chromosomal defects (prevalence ratio, 57.4; 95% confidence interval, 23.7
      138.6) were at the highest risk for MR. Children with nonchromosomal defects,
      including central nervous system defects and all types of organ and system
      defects, were at substantially increased risk for all levels of MR. Risks of MR
      among children with Down syndrome and nonchromosomal defects were not
      substantially altered when adjusted for individual and maternal factors.
      CONCLUSIONS: Children with chromosomal and other structural birth defects are at
      a substantially increased risk for having MR by 7 years of age compared with
      children born without a birth defect. Children with birth defects are at an
      especially increased risk for having severe MR and MR occurring independently of
      other developmental disabilities.

PMID- 12796235
TI  - Developmental, audiological, and speech perception functioning in children after
      cochlear implant surgery.
AB  - OBJECTIVES: To examine changes in audiological, speech perception, and
      developmental functioning subsequent to cochlear implantation in children with
      severe to profound hearing impairment, and to identify factors related to those
      changes. DESIGN: Prospective, longitudinal analysis to compare functioning of
      pediatric patients who underwent cochlear implantation before and 1 year after
      surgery. SETTING: Outpatient pediatric cochlear implantation program in an
      academic institution (The Listening Center, The Johns Hopkins University School
      of Medicine, Baltimore, Md). Patients Forty consecutive pediatric patients
      between 1(1/2) and 9 years of age who received a cochlear implant between April
      1, 1996, and August 31, 1998, and who also underwent psychological, audiological,
      and speech perception evaluations immediately before and 1 year after
      implantation. MAIN OUTCOME MEASURE: Scores on the Bayley Scales of Infant
      Development-Second Edition, Stanford-Binet Intelligence Scale-Fourth Edition,
      Developmental Profile II, Child Behavior Checklist, speech perception categories,
      and audiological pure-tone thresholds. RESULTS: Mean (SD) duration of hearing
      impairment was 37.78 (27.94) months, mean (SD) age at surgery was 50.72 (27.66)
      months. Significant improvements were found 1 year after surgery in audiological,
      speech perception, and developmental functioning, but not in nonverbal
      intelligence or behavior. Greater benefits in audiological and developmental
      functioning were associated with younger age (<48 months) at implantation.
      CONCLUSIONS: Patients showed significant improvement in audiological status,
      overall developmental functioning, and speech perception skills in a short time
      after surgery. Greatest improvement in speech perception was for children with
      the least initial impairment, and greatest developmental gains were associated
      with young age at implantation.

PMID- 12796236
TI  - Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving
      vagal nerve stimulation at a pediatric epilepsy center.
AB  - OBJECTIVE: To determine the outcome of intermittent left vagal nerve stimulation
      on the first 100 consecutive patients treated at our pediatric epilepsy center.
      METHODS: Patients were identified by means of operating room records. Data
      collected described the patient's epilepsy, previous and subsequent therapies,
      adverse events, nonepileptic changes, and outcomes. RESULTS: Average age was 10.4
      years; years of epilepsy, 8.5; total number of antiepileptic therapies, 8.4; and
      median monthly seizure frequency, 120. Data on seizure frequency at follow-up
      were available for 96 of the 100 patients. Forty-five percent of patients
      achieved greater than 50% reduction; and 18% had had no seizures for the last 6
      months. Response was similar in patients with more than 7 years of refractory
      epilepsy as compared with patients with a shorter history. Magnet-generated, on
      demand current reduced seizure intensity in almost half of the patients with
      available data. Generator infections occurred in 3 patients. Twenty-four patients
      had their generators removed. Subsequently, 2 of these patients died.
      CONCLUSIONS: Seizure reduction was the same in patients younger than 12 years and
      12 years or older and in patients with shorter and longer histories of refractory
      epilepsy. Adverse effects were few in this population, particularly in those
      younger than 12 years. Vagal nerve stimulation appears to be a relatively safe
      and potentially effective treatment for children with severely intractable
      epilepsy.

PMID- 12796237
TI  - Oral erythromycin prophylaxis vs watchful waiting in caring for newborns exposed
      to Chlamydia trachomatis.
AB  - BACKGROUND: Chlamydia trachomatis exposure at birth may cause conjunctivitis or
      pneumonia. Until recently, a course of oral erythromycin prophylaxis was
      recommended for C trachomatis-exposed neonates. However, recognition of an
      association between erythromycin and pyloric stenosis prompted a change to a
      watchful waiting recommendation under which only infants who develop symptomatic
      C trachomatis infection are treated with oral erythromycin. OBJECTIVE: To compare
      erythromycin prophylaxis with watchful waiting for a hypothetical cohort of 100
      000 neonates exposed to C trachomatis. METHODS: In a decision tree, potential
      outcomes were C trachomatis conjunctivitis, C trachomatis pneumonia (which could
      require inpatient or outpatient therapy), no clinical disease, and pyloric
      stenosis. Published data were reviewed to derive probability point estimates and
      ranges. Estimated charges served as outcome measures. RESULTS: Watchful waiting
      is less expensive than erythromycin prophylaxis ($15.1 million vs $28.3 million);
      prophylaxis prevents 5986 cases of C trachomatis pneumonia, including 1197
      hospital admissions, but causes 3284 pyloric stenosis cases. (For every 30
      infants given oral erythromycin prophylaxis, one additional case of pyloric
      stenosis would be expected to occur, and approximately 1.8 cases of C trachomatis
      pneumonia would be prevented.) In sensitivity analyses, if more than 3.4% of
      exposed neonates are hospitalized for C trachomatis pneumonia, prophylaxis
      becomes favored. CONCLUSIONS: This study supports the watchful waiting
      recommendation for asymptomatic C trachomatis-exposed neonates. However, there
      are wide plausible ranges for pyloric stenosis risk after erythromycin
      administration and for the incidence of C trachomatis pneumonia severe enough to
      require hospitalization; under some combinations of these rates, prophylaxis
      could be favored.

PMID- 12796238
TI  - Reactions of young adults to September 11, 2001.
AB  - BACKGROUND: Wave III of the National Longitudinal Study of Adolescent Health
      provides opportunities to describe the reactions of young adults to September 11,
      2001, and to increase understanding of the reactions among those who do not
      directly witness disasters. OBJECTIVES: To compare the feelings, perceptions, and
      behaviors of respondents interviewed before with those of respondents interviewed
      within 9 weeks after September 11; and to test the influence of time and distance
      from terrorist sites on pre-post comparisons. DESIGN: Cross-sectional study, with
      comparison groups before and after September 11. SETTING: In-home interviews.
      PARTICIPANTS: Seven thousand ninety-five respondents aged 18 to 26 years. MAIN
      OUTCOME MEASURES: Sadness, psychological distress, closeness to parents,
      importance of religion and spirituality, trust in government, and substance use.
      RESULTS: Male (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI],
      1.08-1.65) and female (aOR, 1.44; 95% CI, 1.22-1.71) respondents interviewed
      after September 11 were more likely to report sadness and increased trust in
      government (aOR range, 2.11-3.30) than those interviewed before September 11.
      Proportions reporting sadness returned to baseline in 4 to 6 weeks; increased
      political trust persisted for the 9-week study period. Male respondents
      interviewed the second week afterwards were more likely to report religious faith
      (aOR, 2.06; 95% CI, 1.40-3.00) and spiritual life (aOR, 1.75; 95% CI, 1.18-2.60)
      as important than were those interviewed before the event. Female respondents
      interviewed afterwards were more likely to report higher levels of psychological
      distress (aOR, 1.40; 95% CI, 1.08-1.83) and closeness to fathers (aOR, 1.36; 95%
      CI, 1.08-1.72). There were no pre-post differences in substance use. Respondents
      closest to terrorist sites were most affected. CONCLUSION: Young adults who did
      not directly witness the events of September 11 experienced reactions that were
      multifaceted and transient--except for persisting trust in government.

PMID- 12796240
TI  - Inaccuracy in parental reporting of the age of their home for lead-screening
      purposes.
AB  - OBJECTIVE: To determine the proportion of children living in pre-1950 housing who
      are correctly identified by parental report as being at risk for lead poisoning.
      DESIGN: Cross-sectional survey of parents. Parents' answers about the age of
      their home were compared with the age of the home found in tax assessor records.
      SETTING: The resident continuity clinic at an urban medical center and 4 private
      pediatric practices. PARTICIPANTS: A convenience sample of 199 parents
      accompanying children to their 9-month to 2-year well-child care visits. All
      parents agreed to participate. Twenty-six were excluded because they lived
      outside the predetermined geographic area or because the age of their home could
      not be confirmed, leaving 173 in the sample. MAIN OUTCOME MEASURE: We calculated
      the sensitivity of asking parents the age of their home in determining which
      children were at risk for lead poisoning because of residence in pre-1950
      housing. RESULTS: According to tax assessor records, 42 children lived in or
      spent time in homes built before 1950. Of these 42 children, 22 of their parents
      reported this exposure when asked, for a sensitivity of 52% (95% confidence
      interval, 37%-67%). If a questionnaire was used to determine whether the child
      should be tested for lead poisoning, 20 of the 42 children who lived in older
      homes would not have been tested. CONCLUSION: Asking parents about the age of
      their home is no better than chance at determining which children are at risk for
      lead poisoning because of residence in older housing.

PMID- 12796239
TI  - Newborn length of stay, health care utilization, and the effect of Minnesota
      legislation.
AB  - OBJECTIVE: To describe newborn length of stay, postdischarge follow-up, and
      health care utilization in the context of Minnesota's early discharge
      legislation. DESIGN AND SETTING: Retrospective study using claims data from a
      large managed care organization. PARTICIPANTS: Term newborns born from January
      1995 through February 1999 (N = 22 944). OUTCOME MEASURES: Newborn length of
      stay, home or clinic visits within 1 week of discharge (early follow-up),
      immunizations completed by age 3 months, readmissions within 1 month of
      discharge, and urgent care or emergency department visits within 2 months of
      discharge. RESULTS: After enactment of Minnesota's early discharge legislation in
      1996, the percentage of newborns with short stays (0-1 days after vaginal birth
      or 2-3 days after cesarean birth) decreased from 52% to 16% for vaginally born
      infants and from 87% to 63% for cesarean-born infants (P =.001). Although the
      legislation mandated coverage for home visits after short stays, only 12.4% of
      short-stay newborns had early home visits. Overall, 50% of infants had early home
      or clinic follow-up; compared with those who did not receive early follow-up,
      these infants were more likely to have complete immunizations (adjusted odds
      ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.14), urgent care or
      emergency department visits (adjusted OR, 1.22; 95% CI, 1.07-1.39), and
      readmissions (adjusted OR, 2.49; 95% CI, 2.02-3.08). CONCLUSIONS: Although
      implementation of Minnesota's early discharge legislation corresponded with
      significantly increased lengths of stay, very few short-stay infants received the
      postdischarge care for which coverage was mandated. Our findings indicate,
      however, that infants at higher risk for adverse outcomes were appropriately
      identified to receive early follow-up.

PMID- 12796241
TI  - How children affect the mother/victim's process in intimate partner violence.
AB  - BACKGROUND: Witnessing intimate partner violence (IPV) causes physical and mental
      health problems for children. Children are one of multiple factors that a victim
      weighs as she manages the abusive relationship. Little has been written about how
      children affect the mother's decisions about the abuse or what assistance a
      mother wants from the children's physician in creating a nonabusive home.
      OBJECTIVE: To consider the role children play in their mothers' management of
      abusive partners. METHODS: Thirty-two mothers living in midwestern IPV shelters
      or participating in support groups were interviewed about their abuse stories,
      perceptions about the effects of the abuse on their children, and desires about
      IPV management in the health care setting. The interviews were audiotaped,
      transcribed, and analyzed by a team of researchers using thematic analysis.
      RESULTS: Children were an integral factor in the mothers' management of their
      abusive relationships. For more than half of the participants, something the
      children did or said catalyzed their seeking help. For some, the children's
      attachment to the abuser was a reason to delay seeking assistance. Based on these
      findings, we explored what mothers wanted from their children's physicians
      regarding their abusive relationships. Mothers talked about the delicate balance
      between education and blame, between offering help and becoming too intrusive,
      and between wanting the best for their children and fearing the involvement of
      child protective services. CONCLUSIONS: Children play an important role in
      mothers' management of their abusive relationships. From their children's
      physicians, participants wanted IPV screening and IPV resources. Some wanted the
      physician to educate them about how the IPV affected the children in a nonblaming
      manner.

PMID- 12796242
TI  - Malnutrition at age 3 years and lower cognitive ability at age 11 years:
      independence from psychosocial adversity.
AB  - BACKGROUND: Early malnutrition is linked to poor cognition, but long-term effects
      have not been extensively examined and psychosocial confounds have not always
      been controlled. OBJECTIVE: To test the hypothesis that malnutrition at age 3
      years will be associated with poorer cognitive ability at age 11 years
      independent of psychosocial confounds. DESIGN: A prospective, longitudinal study
      of a birth cohort of 1559 children originally assessed at age 3 years for
      malnutrition (low hemoglobin level, angular stomatitis, kwashiorkor, and sparse,
      thin hair) and followed up to age 11 years. SETTING AND PARTICIPANTS: A community
      sample of 1559 children (51.4% boys and 48.6% girls) born between September 1,
      1969, and August 31, 1970, in 2 towns in the island of Mauritius, with 68.7%
      Indians and 25.7% Creoles (African origin). MAIN OUTCOME MEASURES: Verbal and
      spatial ability measured at ages 3 and 11 years and reading, scholastic ability,
      and neuropsychologic performance measured at age 11 years. RESULTS: Malnourished
      children had poorer cognition at both ages. Deficits were stable across time,
      applied to all sex and ethnic groups, and remained after controlling for multiple
      measures of psychosocial adversity. Children with 3 indicators of malnutrition
      had a 15.3-point deficit in IQ at age 11 years. CONCLUSIONS: Malnutrition at age
      3 years is associated with poor cognition at age 11 years independent of
      psychosocial adversity. Promoting early childhood nutrition could enhance long
      term cognitive development and school performance, especially in children with
      multiple nutritional deficits.

PMID- 12796243
TI  - Sharing Shigella: risk factors for a multicommunity outbreak of shigellosis.

PMID- 12796244
TI  - Perinatal outcome following third-trimester exposure to paroxetine: an
      alternative interpretation.

PMID- 12796245
TI  - Patient expectations regarding eye care: focus group results.
AB  - BACKGROUND: Increasing emphasis on patient-centered care and other recent
      developments should make patient expectations increasingly important in
      ophthalmology. Motivated by the pivotal role of patient expectations in quality
      of-care assessments and by the limited knowledge about patients' expectations
      regarding eye care, we initiated a pilot study using focus groups to determine a
      relevant set of concerns that patients express as expectations. METHODS: A total
      of 6 focus groups were conducted with patients at Duke University Eye Center
      (Durham, NC). Focus groups ranged in size from 4 to 10 people. The average group
      size was 6. RESULTS: Content analysis of transcripts from the 6 focus groups
      yielded 22 areas of expectations for eye care, which were classified into 5
      categories: communication, interpersonal manner, physician's skill, logistics,
      and other. The 6 areas that appeared to be of greatest importance to focus group
      participants were the following: (1) honesty, (2) information about diagnosis and
      prognosis, (3) explanation in clear language, (4) ophthalmologist's experience
      and reputation, (5) empathy, and (6) listening and addressing concerns.
      CONCLUSIONS: In general, ophthalmology patients in the focus groups emphasized
      expectations related to communication and interpersonal manner. In contrast to
      previous studies with primary care patients, however, ophthalmology patients
      expressed few expectations for technical interventions, such as medication
      prescriptions, physical examination, or diagnostic testing.

PMID- 12796246
TI  - Keratocyte density in the human cornea after photorefractive keratectomy.
AB  - OBJECTIVE: To perform a quantitative analysis of keratocyte density in human
      corneas after photorefractive keratectomy (PRK). METHODS: In a prospective
      comparative trial, 24 eyes of 14 patients received PRK to correct refractive
      errors of between -1.25 diopters (D) and -5.75 D. Corneas were examined by using
      confocal microscopy before and 1 day, 5 days, and 1, 3, 6, 12, 24, and 36 months
      after PRK. Keratocyte nuclei were counted in 5 stromal layers in 3 to 6 scans per
      eye per visit. Keratocyte density in each layer post-PRK was compared with the
      density in the corresponding layer of the pre-PRK full stroma (included stroma
      that would later be photoablated) and the pre-PRK future unablated stroma
      (thickness adjusted by omitting the future ablation depth) (Bonferroni-adjusted
      paired t test). RESULTS: Keratocyte density in the anterior 10% of the post-PRK
      stroma decreased by 25% (P =.002), 41% (P<.001), 40% (P<.001), 43% (P<.001), and
      45% (P<.001) at 3, 6, 12, 24, and 36 months compared with the anterior 10% of the
      pre-PRK full stroma and was reduced by 15% at 36 months (P =.02) compared with
      the anterior 10% of the pre-PRK future unablated stroma. CONCLUSION: After PRK,
      keratocyte density in the anterior stroma is not restored to the high-density
      levels found in the preoperative stroma.

PMID- 12796247
TI  - Patterns of care for open-angle glaucoma in managed care.
AB  - OBJECTIVES: To describe patterns of care for primary open-angle glaucoma (POAG)
      and assess conformance with the American Academy of Ophthalmology's Preferred
      Practice Pattern (PPP). METHODS: We obtained administrative, survey, and eye care
      records data on 395 working-age patients with POAG enrolled in 6 managed care
      plans between 1997 and 1999. We assessed processes of care at the initial and
      follow-up visits, control of intraocular pressure (IOP), intervals between visits
      and visual field tests, and adjustments in therapy. RESULTS: We found high rates
      of performance on most recommended processes during initial evaluations, although
      only 53% of patients received an optic nerve head photograph or drawing and only
      1% had a target IOP level documented. Recommended processes were performed at 80%
      to 97% of follow-up visits. Using loose criteria for control, IOP was controlled
      in 66% of follow-up visits for patients with mild glaucoma and 52% of visits for
      patients with moderate to severe glaucoma. Intervals between visits and visual
      field tests were generally consistent with PPP recommendations. Adjustments in
      therapy were more likely with worse control of IOP, although adjustments occurred
      in only half of visits where the IOP was 30 mm Hg or higher. CONCLUSIONS: Our
      study suggests that, in many respects, patients with POAG are receiving care that
      is consistent with the PPP. However, care is falling short on several key
      aspects, and POAG may be undertreated relative to standards for IOP control
      established in recent clinical trials.

PMID- 12796248
TI  - Progression of age-related macular degeneration: association with body mass
      index, waist circumference, and waist-hip ratio.
AB  - BACKGROUND: Individuals with early or intermediate stages of age-related macular
      degeneration (AMD) make up a large and growing segment of our elderly population.
      To advise these high-risk patients regarding preventive measures, we evaluated
      anthropomorphic, behavioral, and medical factors associated with progression to
      the advanced stages of AMD associated with visual loss. METHODS: The design was a
      prospective cohort study in a hospital-based retinal practice. The 261
      participants were 60 years or older, with some sign of nonadvanced AMD and visual
      acuity of 20/200 or better in at least 1 eye. The average follow-up time was 4.6
      years, and the total person-years of follow-up was 1198. Factors associated with
      rates of progression to advanced AMD were assessed by the Cox proportional
      hazards model. OUTCOME MEASURES: Progression to geographic atrophy and
      neovascular disease. RESULTS: Higher body mass index (calculated as weight in
      kilograms divided by the square of height in meters) increased the risk for
      progression to the advanced forms of AMD. Relative risk (RR) was 2.35 (95%
      confidence interval [CI], 1.27-4.34) for a body mass index of at least 30, and
      2.32 (95% CI, 1.32-4.07) for a body mass index of 25 to 29, relative to the
      lowest category (<25) after controlling for other factors (P =.007 for trend).
      Higher waist circumference was associated with a 2-fold increased risk for
      progression (RR for the highest tertile compared with the lowest, 2.04; 95% CI,
      1.12-3.72), with a significant trend for increasing risk with a greater waist
      circumference (P =.02). Higher waist-hip ratio also increased the risk for
      progression (RR, 1.84; 95% CI, 1.07-3.15) for the highest tertile compared with
      lowest (P =.02 for trend). More physical activity tended to be associated with a
      reduced rate of progression (25% reduction for 3 times per week vigorous activity
      vs none, P =.05 to P =.07). Relative risks for smoking ranged from 1.48 to 1.99,
      but were not statistically significant. CONCLUSIONS: Results provide new
      information regarding modifiable factors for individuals with the early or
      intermediate stages of this disease. Overall and abdominal obesity increased the
      risk for progression to advanced AMD, and more physical activity tended to
      decrease risk. These preventive measures deserve additional research and greater
      emphasis.

PMID- 12796249
TI  - Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the
      NRL gene.
AB  - BACKGROUND: We previously reported an Ser50Thr mutation in the NRL gene as a
      cause of autosomal dominant retinitis pigmentosa. OBJECTIVE: To determine the
      characteristic features of the autosomal dominant retinitis pigmentosa phenotype
      associated with the NRL Ser50Thr mutation in affected individuals from 4 related
      families. METHODS: Clinical records were available for 21 affected individuals; 7
      underwent more extensive electrophysiologic and psychophysical testing. RESULTS:
      Night blindness was the first symptom to manifest, with onset between birth and
      age 16 years. Difficulty with peripheral vision was experienced between 20 and 37
      years of age. Visual acuity was well preserved in younger individuals, but those
      older than 30 years frequently had substantial visual loss (6/36 or worse)
      associated with macular atrophy. Electrophysiologic testing revealed a
      nondetectable scotopic electroretinogram with relative preservation of the
      photopic electroretinogram and pattern electroretinography in the 3 youngest
      patients tested (aged 15-18 years). In older individuals, all components of the
      electroretinogram were nondetectable. Dark-adapted visual fields in younger
      individuals were greatly impaired, but their photopic fields remained relatively
      well preserved. Older patients had photopic fields limited to just a few degrees.
      Distinctive peripapillary chorioretinal atrophy seems to develop as the disorder
      progresses. CONCLUSIONS: The NRL Ser50Thr mutation is associated with selective
      loss of scotopic function before age 20 years. With time, however, the photopic
      system becomes affected, leading to loss of the photopic visual field and of
      visual acuity.

PMID- 12796250
TI  - Retinal function in carriers of Bardet-Biedl syndrome.
AB  - OBJECTIVE: To test the hypothesis that carriers of Bardet-Biedl syndrome have
      abnormal rod-mediated responses. METHODS: Parents (n = 26) of children with
      Bardet-Biedl syndrome (BBS), who are obligate carriers of BBS, consented to
      scotopic, full-field electroretinography (ERG). Responses were recorded over a 4
      to 5 log unit range, up to a maximum stimulus of approximately +3.6 log scotopic
      troland seconds. The parameters of activation of the rod photoresponse, S
      (sensitivity parameter) and Rmp3(amplitude of the saturated rod response), were
      derived by fitting a transduction model to the ERG a-waves. For the b-wave, the
      stimulus producing a half maximum response (log sigma) and the saturated
      amplitude (Vmax) were determined. The model of the rod photoresponse was
      subtracted from the intact ERG to demonstrate a corneal positive potential (P2),
      and log kP2 and P2max were determined. The carriers' ERG responses were compared
      with those of healthy control subjects (n = 26). MAIN OUTCOME MEASURES:
      Sensitivity (S, log sigma, and log kP2) and saturated amplitude (Rmp3, Vmax, and
      P2max) of receptoral and postreceptoral response components. RESULTS: All parents
      had decreased P2 sensitivity, and most (15 [60%] of 26) had decreased b-wave
      sensitivity. The rod photoresponse sensitivity and the saturated amplitudes of
      the rod cell response, b-wave and P2, did not differ significantly between
      carriers and controls. CONCLUSIONS: Diminished P2 sensitivity is characteristic
      of the carriers of BBS. The site of the primary defect in the BBS rod pathway
      appears to be proximal to the outer segments, most likely before the rod-bipolar
      cell synapse.

PMID- 12796251
TI  - Retinal function abnormalities in patients treated with vigabatrin.
AB  - OBJECTIVE: To evaluate central and peripheral retinal function in patients
      treated with vigabatrin, an antiepileptic drug associated with peripheral visual
      field constriction (VFC). METHODS: Six patients with epilepsy treated with
      vigabatrin as add-on therapy for at least 3 years were included in this
      observational case series. All patients underwent a clinical ophthalmologic
      examination, color vision testing, standard perimetry, and full-field and focal
      foveal cone electroretinography. Four patients, 3 of whom had VFC, completed
      specialized computerized static light- and dark-adapted perimetry. RESULTS: In 9
      of 11 eyes tested, foveal cone electroretinographic amplitudes were at or below
      the lower limit of normal. Dark-adapted perimetry demonstrated abnormal rod
      derived visual fields in the 3 patients with vigabatrin-attributed VFC, whereas
      rod-derived thresholds were within normal limits throughout the visual field in
      the patient who did not have VFC. CONCLUSIONS: Our results suggest that
      vigabatrin not only impairs peripheral cone-derived function as manifested by VFC
      but also affects foveal cone electroretinographic amplitudes and rod-derived
      visual fields. The clinical dilemma regarding the use of vigabatrin therapy is
      further complicated since central as well as peripheral visual function seems to
      be adversely affected.

PMID- 12796252
TI  - Large-spot size transpupillary thermotherapy for the treatment of occult
      choroidal neovascularization associated with age-related macular degeneration.
AB  - OBJECTIVE: To describe the outcome of patients with occult choroidal
      neovascularization in age-related macular degeneration treated with
      transpupillary thermotherapy. DESIGN: Prospective, nonrandomized, nonmasked case
      series. METHODS: All patients with age-related macular degeneration with a
      predominantly occult choroidal neovascular membrane and an initial visual acuity
      of 20/400 or better were offered treatment using transpupillary thermotherapy.
      The treatment consisted of using a diode laser, a spot size of about 3000 to 6000
      micro m delivered over 60 seconds, and a power of 600 to 1000 mW. MAIN OUTCOME
      MEASURES: A stable, improved, or worsened visual acuity and the need for
      additional treatment. RESULTS: Sixty-nine patients were treated. All patients
      have been followed up for at least 6 months. At the 6-, 9-, and 12-month follow
      up visits, 71% of patients have stable or improved visual acuity and 29% have
      lost 2 or more lines of visual acuity on the Snellen letter chart. CONCLUSION:
      Large-spot size transpupillary thermotherapy is effective in stabilizing the
      visual acuity in those patients who have occult choroidal neovascularization due
      to age-related macular degeneration.

PMID- 12796253
TI  - Axial length-disc area ratio in esotropic amblyopia.
AB  - BACKGROUND: Hyperopia is a risk factor for esotropia and amblyopia. A previous
      study indicated that disc areas (DAs) are reduced in patients with amblyopia.
      OBJECTIVE: To determine if there is a difference in the relative size of the
      optic disc in hyperopic eyes without strabismus or amblyopia compared with
      esotropic and amblyopic eyes, the relationship of axial length (AXL) to DA in
      subjects with hyperopia was evaluated. METHODS: Eight hundred fifty records from
      my private practice, which included AXL measurements and optic disc photographs
      or digital images, were analyzed to locate 122 subjects with bilateral refractive
      errors greater than +2.00 diopters. Disc areas were measured using objective
      techniques. Axial lengths were determined by ultrasonographic biometry. A ratio,
      AXL/DA, was derived by dividing the AXL in millimeters by the DA in square
      millimeters. RESULTS: The mean (SD) AXL/DA for the group with hyperopia was 9.48
      (2.70) mm and 12.30 (3.45) mm for the group with hyperopic strabismus (P =.01).
      The mean (SD) AXL/DA was 15.24 (4.61) mm in the amblyopic eyes and 13.61 (3.67)
      mm for the nonamblyopic fellow eye (P =.02). CONCLUSION: The optic discs of eyes
      with hyperopic strabismus with and without amblyopia were disproportionately and
      markedly reduced when compared with hyperopic eyes without amblyopia or
      esotropia.

PMID- 12796254
TI  - High expression of chemokines Gro-alpha (CXCL-1), IL-8 (CXCL-8), and MCP-1 (CCL
      2) in inflamed human corneas in vivo.
AB  - OBJECTIVE: To investigate in vivo expression of chemokines in normal and inflamed
      human corneas, to determine whether chemokines are responsible for the
      recruitment of inflammatory cells. METHODS: In situ hybridization of the CXC
      chemokines growth-related oncogene-alpha (Gro-alpha) (CXCL-1), interleukin 8
      (CXCL-8), macrophage interferon-gamma inducible gene (CXCL-9), and interferon
      gamma inducible protein 10 (CXCL-10) and of the CC chemokines macrophage
      chemoattractant protein 1 (MCP-1) (CCL-2), macrophage inflammatory protein 1alpha
      (CCL-3), and regulated on activation, normal T-cell expressed and secreted (CCL
      5) was performed to localize chemokine messenger RNA. Immunohistochemistry was
      used to identify the cellular infiltrate within the cornea. Three normal human
      eyes were compared with eyes enucleated because of chronic inflammation (n = 10),
      secondary to perforating injuries. RESULTS: In normal corneas, no chemokine
      expression was detected. In inflamed lesions, a high intensity of signals from
      Gro-alpha (CXCL-1) and MCP-1 (CCL-2) messenger RNA was observed in limbal
      epithelium and from Gro-alpha (CXCL-1), interleukin 8 (CXCL-8), and MCP-1 (CCL-2)
      in corneal stroma. The Gro-alpha (CXCL-1) was the only chemokine expressed by
      central corneal epithelium. All other examined chemokines were only moderately
      expressed in limbus and corneal stroma, or barely detectable. CONCLUSIONS: These
      cytokines are important agents in the cytokine network and contribute to the cell
      specific and spatially restricted recruitment of neutrophils and mononuclear
      cells in acute inflammatory lesions of the human cornea. Clinical Relevance
      Understanding the role of chemokines in corneal inflammation may lead to the
      development of a selective receptor blockage of highly expressed chemokines to
      inhibit the recruitment of leukocyte subsets.

PMID- 12796255
TI  - Human lens epithelial cell damage and stimulation of their secretion of chemical
      mediators by benzalkonium chloride rather than latanoprost and timolol.
AB  - OBJECTIVE: To investigate the effects of latanoprost, timolol maleate, and
      benzalkonium chloride on cell damage and induction of the secretion of chemical
      mediators of stress and wound healing by human lens epithelial cells in culture.
      METHODS: Cells from a human lens epithelial cell line (SRA01/04) were cultured in
      Dulbecco minimum essential medium supplemented with 5% fetal bovine serum. The
      amounts of latanoprost (50 micro g/mL), timolol maleate (5 mg/mL), or
      benzalkonium chloride (200 micro g/mL) used in eyedrops, and x10 to x1000
      dilutions thereof, were added to the medium. After 7 days' culture, cell
      morphological changes were assessed using phase-contrast microscopy, and cell
      free culture supernatants were collected for prostaglandin E2 (PGE2), interleukin
      1alpha (IL-1alpha), and interleukin 6 (IL-6) iodine I 125 radioimmunoassay,
      enzyme-linked immunosorbent assay, and chemiluminescent enzyme immunoassay,
      respectively. RESULTS: All cells that were cultured with the concentrations of
      latanoprost, timolol, or benzalkonium chloride used in eyedrops detached from the
      culture dish and died within 3 days. At a x10 dilution of latanoprost or timolol
      or a x100 dilution of benzalkonium chloride, no proliferation or elongation of
      the cells was observed. Secretions of PGE2, IL-1alpha, and IL-6 at x10 dilutions
      of latanoprost or timolol were 3 to 77 times higher than in controls, whereas
      they were 190 to 305 times higher at a x180 dilution of benzalkonium chloride.
      The amounts of these soluble mediators in culture supernatants depended on the
      dose of latanoprost, timolol, or benzalkonium chloride added. CONCLUSION: Our
      results indicate that benzalkonium chloride, used as the preservative in eyedrops
      containing latanoprost or timolol, is the agent most damaging to lens epithelial
      cells and most strongly stimulates the expression of soluble chemical mediators
      in these cells.

PMID- 12796256
TI  - Human corneal endothelial cell expression of Na+,K+-adenosine triphosphatase
      isoforms.
AB  - OBJECTIVE: To determine the expression of alpha subunits and different isozymes
      of Na+,K+-adenosine triphosphatase (ATPase) in human corneal endothelial cells
      (HCECs). METHODS: Immunoblot and RNA analysis of Na+,K+-ATPase alpha subunit
      expression were performed in preparations from HCECs that had been immortalized
      by transformation with simian virus 40. Na+,K+-ATPase activity was determined by
      constructing dose-response curves for the ouabain inhibition of Na+,K+-ATPase
      activity in human corneal endothelial cells. RESULTS: Both messenger RNA analysis
      and immunoblot studies indicated that HCECs express ATPase catalytic alpha1 and
      alpha3, but not alpha2 and alpha4, subunits. A limited amount of alpha3 subunit
      was expressed in HCECs compared with the alpha1 subunit. Biochemical analyses of
      Na+,K+-ATPase activity revealed 2 independently active Na+,K+-ATPase isoenzymes,
      a low-affinity site with a kinetic parameter for ouabain inhibition constant (Ki)
      in the micromolar range and a high-affinity site with a constant Ki in the
      nanomolar range. These 2 sites may be associated with alpha1 and alpha3 isoforms,
      respectively, expressed in HCECs. CONCLUSIONS: Human corneal endothelial cells
      express alpha1 and alpha3 isoforms of Na+,K+-ATPase, and both polypeptides are
      catalytically competent in these cells. Defining the components of Na+,K+-ATPase
      in HCECs is an important step toward elucidating the mechanisms that regulate
      corneal endothelial ionic pump function as well as the pathogenesis of corneal
      diseases associated with corneal edema.

PMID- 12796257
TI  - Immunohistochemical and molecular genetic evidence for type IV collagen alpha5
      chain abnormality in the anterior lenticonus associated with Alport syndrome.
AB  - OBJECTIVE: To present evidence for a type IV collagen alpha5 chain (alpha5[IV])
      abnormality in the anterior lens capsule of a patient with anterior lenticonus
      associated with Alport syndrome. METHODS: The anterior lens capsule obtained from
      a 54-year-old man with anterior lenticonus associated with Alport syndrome was
      examined ultrastructurally and stained immunohistochemically for the alpha chains
      of type IV collagen, alpha1(IV) to alpha6(IV). A search was also made for a
      mutation in the COL4A5 complementary DNA encoding the alpha5(IV) chain by reverse
      transcription-polymerase chain reaction of illegitimate transcripts. RESULTS: The
      anterior lens capsule of the patient was much thinner than that of normal
      subjects and lacked the alpha3(IV) to alpha6(IV) chains immunohistochemically,
      while control specimens stained positively for all of the alpha(IV) chains. The
      patient had a C-to-T transition at nucleotide 5231 causing a nonsense mutation,
      R1677X, in the COL4A5 complementary DNA. CONCLUSION: Our findings demonstrated
      that normal anterior lens capsules express all of the alpha(IV) chains and that a
      patient with anterior lenticonus associated with Alport syndrome had a mutation
      in the COL4A5 gene resulting in the lack of immunoreactivity to alpha3(IV) to
      alpha6(IV) chains in the anterior lens capsule. Clinical Relevance This study
      showed abnormal composition of alpha(IV) chains in the anterior lens capsule of a
      patient with anterior lenticonus caused by a nonsense mutation in the COL4A5
      gene. Further investigation of the phenotype-genotype relationship will provide a
      better understanding of the molecular pathogenesis of anterior lenticonus.

PMID- 12796258
TI  - ABCA4 gene sequence variations in patients with autosomal recessive cone-rod
      dystrophy.
AB  - OBJECTIVE: To identify sequence variations in the ABCA4 gene in a cohort of
      patients with autosomal recessive cone-rod dystrophy. METHODS: The coding
      sequences of the ABCA4 gene were analyzed in 30 unrelated probands. In those
      patients with plausible disease-causing variations, correlations were made
      between genotype and fundus phenotype as well as with electrophysiological and
      visual field findings. RESULTS: Sixteen (53%) of 30 probands were found to harbor
      plausible disease-causing variations in the ABCA4 gene. Two distinctly different
      fundus phenotypes were observed in our cohort of patients. Twelve patients showed
      diffuse pigmentary degenerative changes, whereas 4 showed either no pigmentary
      changes or only a mild degree of peripheral pigment degeneration. An associa-tion
      between certain sequence variations and each of these 2 different phenotypes was
      observed. CONCLUSIONS: Our findings confirm that a substantial percentage of
      patients with autosomal recessive cone-rod dystrophy are likely to harbor a
      mutation in the ABCA4 gene as the cause of their disease. The fundus phenotype
      observed in such patients is quite variable, and certain fundus phenotypes may be
      more associated with certain genotypes. Clinical Relevance Identification of the
      molecular genetic basis for various inherited human retinal dystrophies, such as
      cone-rod dystrophy, facilitates a potentially better understanding of the
      mechanisms by which photoreceptor cells degenerate. This in turn provides
      guidance as to how to better proceed in identifying the most optimal future
      therapeutic strategies.

PMID- 12796259
TI  - Factors related to the 4-year risk of high intraocular pressure: the Barbados Eye
      Studies.
AB  - OBJECTIVE: To evaluate the 4-year risk of high intraocular pressure (IOP) and
      associated factors in a black population without glaucoma at baseline. DESIGN:
      Population-based incidence study. PARTICIPANTS: Random sample of Barbados
      residents aged 40 to 84 years. After 4 years, 3427 (85%) were reexamined. MAIN
      OUTCOME MEASURES: Development of elevated IOP (using percentile-based
      definitions) among individuals with an IOP of 21 mm Hg or lower and no glaucoma
      at baseline. Associations were evaluated using polychotomous logistic regression.
      RESULTS: At baseline, 2856 participants did not have glaucoma or suspected
      glaucoma: 361 had an IOP higher than 21 mm Hg or received treatment, and 2495 had
      an IOP of 21 mm Hg or lower and no treatment. At follow-up, only 58% of the 361
      participants remained free of glaucoma and had an IOP higher than 21 mm Hg,
      whereas 30% had an IOP of 21 mm Hg or lower. Among the remaining 2495
      participants, the incidence of IOP higher than 21 mm Hg or treatment (80th
      percentile) was 12.9% (95% confidence interval, 11.7%-14.3%). Using other
      definitions of elevated IOP, estimates ranged from 1.5% to 11%. Incidence
      increased with age, with rates 2.5 times higher at 70 years or older than at ages
      40 to 49 years. Factors associated with high IOP included age, baseline IOP,
      hypertension, and blood pressure. Whereas participants with an IOP between 21 mm
      Hg and 28 mm Hg had higher blood pressure readings, those with an IOP of 21 mm Hg
      or lower or an IOP higher than 28 mm Hg had similar values. CONCLUSIONS:
      Definitions of high IOP based on percentiles may be more applicable than those
      based on arbitrary values. Older individuals with a higher baseline IOP were more
      likely to develop elevated IOP after 4 years. Although blood pressure was also
      associated with high IOP, the relationship may be nonlinear.

PMID- 12796260
TI  - Exfoliation syndrome in black South Africans.
AB  - BACKGROUND: Data on exfoliation syndrome (XFS) in Africans are scarce. OBJECTIVE:
      To determine the prevalence and clinical features of XFS among black South
      Africans. DESIGN: Random cross-sectional samples of the black population aged 40
      years or older from 2 districts in South Africa: Hlabisa, in northern KwaZulu
      Natal Province, and Temba, North West Province. METHODS: Standardized
      examination, including slitlamp biomicroscopy with pupil dilatation, gonioscopy,
      pachymetry, tonometry, binocular indirect ophthalmoscopy, and visual field
      testing. RESULTS: Among 1840 participants, the prevalence of XFS was 7.7% (95%
      confidence interval, 5.4%-10.5%) in Hlabisa and 6.0% (95% confidence interval,
      4.1%-8.4%) in Temba. The prevalence increased with age, with 18.9% (Hlabisa) and
      16.5% (Temba) of those 70 or older affected. The clinical appearance was similar
      to that reported in other ethnic groups. Exfoliative glaucoma accounted for
      approximately one fourth of open-angle glaucoma cases (OAG). Open-angle glaucoma
      was associated with XFS; the age-adjusted and sex-adjusted odds ratios were 2.3
      (95% confidence interval, 1.0-5.2) and 2.8 (95% confidence interval, 1.2-6.3) for
      Hlabisa and Temba, respectively. The relationship with OAG was absent when
      adjusting for intraocular pressure. Exfoliative glaucoma was characterized in
      this predominantly untreated population by high intraocular pressure and severe
      visual loss. Among subjects with XFS and OAG, 16 of 18 were blind in 1 or both
      eyes. CONCLUSIONS: Exfoliation syndrome occurs at a high prevalence among black
      South Africans and incurs a moderate increase in risk of glaucoma. In this
      untreated population, this increased risk was dependent on raised intraocular
      pressure. Open-angle glaucoma in association with XFS appears to be associated
      with a poor prognosis.

PMID- 12796261
TI  - Precision and safety of the pulsed electron avalanche knife in vitreoretinal
      surgery.
AB  - BACKGROUND: We have developed a new surgical instrument, called the pulsed
      electron avalanche knife (PEAK; Carl Zeiss Meditec, Jena, Germany), for precise,
      "cold," and tractionless dissection of tissue in liquid media. OBJECTIVE: To
      evaluate the 3-dimensional damage zone induced by the PEAK compared with 2 other
      standard intraocular surgical instruments, diathermy and retinal scissors.
      METHODS: Damage zone and minimum safe distance were measured in vitro on chick
      chorioallantoic membrane and in vivo on rabbit retina with the use of propidium
      iodide staining. RESULTS: The PEAK produced a paracentral zone of cellular
      structure disruption surrounding a crater and a peripheral zone of structurally
      intact but abnormally permeable cells. The instrument induced a damage radius
      that varied from 55 to 300 micro m for the range of voltages and pulses typically
      used during surgery. For comparison, damage radius for microsurgical scissors was
      50 micro m, and for diathermy, 400 to 850 micro m. The PEAK also damaged tissue
      up to 1.4 mm away by the creation of water flow that formed at the tip of convex
      probes during collapse of a cavitation bubble. Concave probes, which prevent
      formation of the water jet, eliminated this effect. CONCLUSIONS: The PEAK
      operated well within accept-able safety limits and may greatly facilitate both
      posterior segment surgeries (eg, membrane dissection and sheathotomy) and
      anterior segment procedures (eg, capsulotomy, nonpenetrating trabeculectomy, and
      iridectomy).

PMID- 12796262
TI  - Pieter Pauw's tumor oculorum: reappraisal of the presumed first description of
      retinoblastoma in 1597.
AB  - Cancer in a young child is unusual and has always aroused curiosity. Proptosis
      and an enormous, rapidly growing unilateral tumor in a 3-year-old boy prompted
      Pieter Pauw (1564-1617), a 16th-century anatomist, to perform an autopsy. His
      published notes from the autopsy were rediscovered in the 19th century, first by
      the German ophthalmologist and historian Julius Hirschberg and then by Edwin B.
      Dunphy, from Boston, Mass, who suggested that the child suffered from
      retinoblastoma, an interpretation that has held sway. Critical translation of the
      original Latin text suggests that an orbital tumor, such as embryonal
      rhabdomyosarcoma, would equally well explain Pauw's observations. His description
      also gives insight into the concept of a mole as a congenital as well as an
      intrauterine tumor in Renaissance medicine.

PMID- 12796263
TI  - Professor Ernst Fuchs (1851-1930): a defining career in ophthalmology.
AB  - Although his name is commonly recognized in conjunction with various corneal and
      anterior segment disorders, Ernst Fuchs' contribution to ophthalmology exceeds
      purely the delineation of ocular diseases and the detailed description of signs.
      Fuchs' collection of microscopic samples laid the foundation for anatomical and
      pathological understanding of blood vessels, muscles, and most other tissues of
      the eye. Additionally, Fuchs was able to pass on his unique knowledge, educating
      ophthalmologists at an international level. His textbook was, for many decades,
      the most extensively used reference book in the field of ophthalmology worldwide.

PMID- 12796264
TI  - Does benzalkonium chloride cause cataract?

PMID- 12796265
TI  - Pocket of fluid in the lamellar interface after penetrating keratoplasty and
      laser in situ keratomileusis.

PMID- 12796266
TI  - Histopathological analysis of the cornea after laser in situ keratomileusis.

PMID- 12796267
TI  - Choroidal neovascular membranes treated with photodynamic therapy.

PMID- 12796268
TI  - Preexisting endothelial abnormalities in bilateral postoperative descemet
      membrane detachment.

PMID- 12796269
TI  - Iatrogenic corneal and conjunctival toxic reaction from hydrogen peroxide
      disinfection.

PMID- 12796270
TI  - Congenital iris bombe induced by large iris cysts.

PMID- 12796271
TI  - Optic neuropathy secondary to sub-tenon anesthetic injection in cataract surgery.

PMID- 12796272
TI  - Detection of lactate in the human vitreous body using proton magnetic resonance
      spectroscopy.

PMID- 12796273
TI  - Herpes simplex virus dacryoadenitis in an immunocompromised patient.

PMID- 12796274
TI  - The retinal features of acute zonal occult outer retinopathy (AZOOR).

PMID- 12796275
TI  - Bilateral retinoblastoma, microphthalmia, and colobomas in the 13q deletion
      syndrome.

PMID- 12796277
TI  - Iatrogenic projectile injuries during eye surgery.

PMID- 12796276
TI  - Bobcat bite injury of the eye and ocular adnexa.

PMID- 12796278
TI  - Exfoliation syndrome among Azerbaijani.

PMID- 12796279
TI  - Foveal hypoplasia and other ocular signs: a possible case of incontinentia
      pigmenti?

PMID- 12796280
TI  - Blockade of the renin-angiotensin system increases adiponectin concentrations in
      patients with essential hypertension.
AB  - Adiponectin, an adipocyte-derived protein, has been suggested to play an
      important role in insulin sensitivity. We examined the association between
      insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic
      glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT)
      and 20 normotensives (NT) and investigated the effect of blockade of the renin
      angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12
      insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean
      1 SD of the M value in NT. There were no intergroup differences in age, gender,
      and body mass index (BMI). EHT-R had significantly higher levels of insulin and
      triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had
      higher levels of free fatty acid and lower levels of high-density lipoprotein
      (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively
      correlated with M value and HDL cholesterol and negatively correlated with BMI,
      insulin, free fatty acid, and triglyceride but not with blood pressure. M value,
      BMI, and HDL cholesterol were independent determinants of adiponectin
      concentrations in multiple and stepwise regression analyses. Sixteen EHT were
      treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9)
      or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks.
      Treatment with temocapril or candesartan significantly decreased blood pressure
      and increased M value and adiponectin concentrations but did not affect BMI and
      HDL cholesterol. These results suggest that hypoadiponectinemia is related to
      insulin resistance in essential hypertension and that RAS blockade increases
      adiponectin concentrations with improvement in insulin sensitivity.

PMID- 12796281
TI  - Middle age cardiovascular risk factors and abdominal aortic aneurysm in older
      age.
AB  - Few prospective studies have examined associations between major cardiovascular
      risk factors and occurrence of abdominal aortic aneurysm; findings from cross
      sectional studies are inconsistent. This long-term population-based study
      assessed relationships of major risk factors in middle-age to clinical nonfatal
      plus fatal abdominal aortic aneurysm in older-age in the Chicago Heart
      Association Detection Project in Industry cohort--10 574 men and 8700 women
      baseline ages 40 to 64 years screened for risk factors in 1967-1973 at
      workplaces. With average follow-up of 30 years and clinical cases identified from
      Medicare records and death certificates, risk factor relationships to abdominal
      aortic aneurysm occurrence were assessed by Cox regression. There were among men
      309 cases and among women, 109--most from Medicare records. Most findings were
      qualitatively similar for men and women. In multivariate analyses (5 models),
      hazard ratios for abdominal aortic aneurysm were significantly greater for men
      than women (> or =1.97), with older age (> or =1.63/5 years), higher serum
      cholesterol (> or =1.30/40.0 mg/dL), cigarettes/d (> or =2.43/20 cigarettes),
      past smoking (> or =1.41), height (> or =1.17/7 cm), evidence of adverse blood
      pressure (hazard ratio 1.10/20 mm Hg higher systolic pressure, 1.12 to 1.14/12 mm
      Hg higher diastolic pressure, 1.87 with history of treated hypertension). It is
      concluded that major cardiovascular risk factors--serum cholesterol, smoking, and
      blood pressure--in middle age relate significantly to risk of abdominal aortic
      aneurysm in persons surviving into older age.

PMID- 12796282
TI  - Primary aldosteronism and hypertensive disease.
AB  - Recent studies in hypertensive populations that have used the serum aldosterone
      (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a
      high prevalence of primary aldosteronism (PA). This frequency is higher than that
      previously described when hypokalemia was used as a screening tool. However,
      other factors, such as the characteristics of hypertensive disease, could also
      influence the prevalence of PA. We studied 609 essential hypertensive patients,
      classified according to the Joint National Committee VI (JNC VI), in 3 different
      stages depending on the severity of their hypertensive disease. We measured SA
      and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio >25 was
      detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA
      diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension
      stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases
      (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger
      than the other hypertensive patients (48.4+/-10.5 vs 53.6+/-10.2 years; P<0.05).
      Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had
      minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement
      in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of
      PA in essential hypertensives classified in stages 2 and 3 according to the JNC
      VI. The low frequency of computed tomography scan abnormalities and hypokalemia
      suggests that the diagnosis for most PA patients corresponds to attenuated forms
      of the disease.

PMID- 12796283
TI  - Regulation of the transcriptional response to oxidative stress in fungi:
      similarities and differences.

PMID- 12796284
TI  - Relationship between switching and mating in Candida albicans.

PMID- 12796285
TI  - Asynchronous cell cycle and asymmetric vacuolar inheritance in true hyphae of
      Candida albicans.
AB  - Candida albicans forms unconstricted hyphae in serum-containing medium that are
      divided into discrete compartments. Time-lapse photomicroscopy, flow cytometry,
      and a novel three-dimensional imaging system were used to demonstrate that the
      kinetics and cell cycle events accompanying hyphal development were correlated
      with dynamic changes in vacuole morphology and the pattern of vacuole
      inheritance. Apical cells of hyphae underwent continuous extension before and
      after the first cytokinesis event. However, the resulting mother cell and sub
      apical compartments did not immediately reenter the cell cycle and instead
      underwent cell cycle arrest before reentering the cycle. Vacuole was inherited
      asymmetrically at cytokinesis so that the distal, arrested compartments inherited
      most vacuole and the growing apical cell inherited most cytoplasm. Hydroxyurea
      release experiments demonstrated that the arrested, vacuolated hyphal
      compartments were in the G(1) phase of the cycle. The period of cell cycle arrest
      was decreased by the provision of assimilatable forms of nitrogen, suggesting
      that the hyphal cell cycle is regulated by nitrogen limitation that results in
      sup-apical cell cycle arrest. This pattern of growth is distinct from that of the
      synchronous, symmetrical development of pseudohyphae of C. albicans and other
      yeast species. These observations suggest that the cellular vacuole space
      correlates with alterations in the cell cycles of different cell types and that
      the total organelle space may influence size-regulated functions and hence the
      timing of the eukaryotic cell cycle.

PMID- 12796286
TI  - Candida albicans VPS11 is required for vacuole biogenesis and germ tube
      formation.
AB  - The Candida albicans vacuole has previously been observed to undergo rapid
      expansion during the emergence of a germ tube from a yeast cell, to occupy the
      majority of the parent yeast cell. Furthermore, the yeast-to-hypha switch has
      been implicated in the virulence of this organism. The class C vps (vacuolar
      protein sorting) mutants of Saccharomyces cerevisiae are defective in multiple
      protein delivery pathways to the vacuole and prevacuole compartment. In this
      study C. albicans homologues of the S. cerevisiae class C VPS genes have been
      identified. Deletion of a C. albicans VPS11 homologue resulted in a number of
      phenotypes that closely resemble those of the class C vps mutants of S.
      cerevisiae, including the absence of a vacuolar compartment. The C. albicans
      vps11Delta mutant also had much-reduced secreted lipase and aspartyl protease
      activities. Furthermore, vps11Delta strains were defective in yeast-hypha
      morphogenesis. Upon serum induction of filamentous growth, mutants showed delayed
      emergence of germ tubes, had a reduced apical extension rate compared to those of
      control strains, and were unable to form mature hyphae. These results suggest
      that Vps11p-mediated trafficking steps are necessary to support the rapid
      emergence and extension of the germ tube from the parent yeast cell.

PMID- 12796288
TI  - Ady4p and Spo74p are components of the meiotic spindle pole body that promote
      growth of the prospore membrane in Saccharomyces cerevisiae.
AB  - Spore formation in Saccharomyces cerevisiae occurs via the de novo synthesis of
      the prospore membrane during the second meiotic division. Prospore membrane
      formation is triggered by assembly of a membrane-organizing center, the meiotic
      outer plaque (MOP), on the cytoplasmic face of the spindle pole body (SPB) during
      meiosis. We report here the identification of two new components of the MOP,
      Ady4p and Spo74p. Ady4p and Spo74p interact with known proteins of the MOP and
      are localized to the outer plaque of the SPB during meiosis II. MOP assembly and
      prospore membrane formation are abolished in spo74Delta/spo74Delta cells and
      occur aberrantly in ady4Delta/ady4Delta cells. Spo74p and the MOP component
      Mpc70p are mutually dependent for recruitment to SPBs during meiosis. In
      contrast, both Ady4p and Spo74p are present at SPBs, albeit at reduced levels, in
      cells that lack the MOP component Mpc54p. Our findings suggest a model for the
      assembled MOP in which Mpc54p, Mpc70p, and Spo74p make up a core structural unit
      of the scaffold that initiates synthesis of the prospore membrane, and Ady4p is
      an auxiliary component that stabilizes the plaque.

PMID- 12796287
TI  - Calcineurin is essential for Candida albicans survival in serum and virulence.
AB  - Calcineurin is a calcium-activated protein phosphatase that is the target of the
      immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls
      nuclear import of the NF-AT transcription factor and gene activation. In plants
      and fungi, calcineurin functions in stress responses (e.g., temperature, cations,
      and pH) and is necessary for the virulence of the fungal pathogen Cryptococcus
      neoformans. Here we show that calcineurin is also required for the virulence of
      another major fungus that is pathogenic to humans, Candida albicans. C. albicans
      calcineurin mutants had significantly reduced virulence in a murine model of
      systemic infection. In contrast to its role in C. neoformans, calcineurin was not
      required for C. albicans survival at 37 degrees C. Moreover, C. albicans
      calcineurin mutant strains exhibited no defects in known Candida virulence traits
      associated with host invasion, including filamentous growth, germ tube formation,
      and adherence to and injury of mammalian cells. C. albicans calcineurin mutant
      strains failed to colonize and grow in the kidneys of infected animals and were
      unable to survive when exposed to serum in vitro. Our studies illustrate that
      calcineurin has evolved to control aspects of the virulence of two divergent
      fungal pathogens via distinct mechanisms that can be targeted to achieve broad
      spectrum antifungal action.

PMID- 12796289
TI  - TmkA, a mitogen-activated protein kinase of Trichoderma virens, is involved in
      biocontrol properties and repression of conidiation in the dark.
AB  - Trichoderma virens is a mycoparasitic fungus used in biocontrol of soilborne
      plant pathogens. It inhibits or kills plant-pathogenic fungi through production
      of antifungal antibiotics and parasitism of hyphae and sclerotia. Conidiation, or
      the production of asexual spores, an inducible process triggered by light or
      nutrient stress, is an important trait in survival and also development of
      formulation products. In many fungi, signaling pathways, including mitogen
      activated protein kinase (MAPK) cascades, have been implicated in parasitism of
      host plants as well as in the production of asexual spores. Here, we have studied
      the role of a MAPK gene, that for TmkA, in conidiation and antagonistic
      properties of a biocontrol strain of T. virens. Through single- and double
      crossover recombination, we obtained three tmkA loss-of-function mutants. The
      TmkA transcript was not detectable in these mutants. The mutants conidiated in
      the dark, although photoinduction was normal and the light sensitivities of the
      wild type and the mutant were the same. The mutants had, overall, normal colony
      morphology, but their radial growth rate was reduced by about 16%, with no
      decrease in biomass production. Against Rhizoctonia solani hyphae, the knockout
      mutants exhibited mycoparasitic coiling and lysis of host hyphae similar to that
      of the wild type. The mutants, however, were less effective in colonizing the
      sclerotia of R. solani. On Sclerotium rolfsii, the MAPK loss-of-function mutants
      had reduced antagonistic properties in confrontation assays and failed to
      parasitize the sclerotia. TmkA-dependent and -independent pathways are thus
      involved in antagonism against different hosts. Finally, in contrast to the case
      for other filamentous fungi studied so far, signaling through a MAPK represses,
      rather than induces, asexual sporulation.

PMID- 12796290
TI  - Roles of tyrosine-rich precursor glycoproteins and dityrosine- and 3,4
      dihydroxyphenylalanine-mediated protein cross-linking in development of the
      oocyst wall in the coccidian parasite Eimeria maxima.
AB  - The oocyst wall of apicomplexan parasites protects them from the harsh external
      environment, preserving their survival prior to transmission to the next host. If
      oocyst wall formation could be disrupted, then logically, the cycle of disease
      transmission could be stopped, and strategies to control infection by several
      organisms of medical and veterinary importance such as Eimeria, Plasmodium,
      Toxoplasma, Cyclospora, and Neospora could be developed. Here, we show that two
      tyrosine-rich precursor glycoproteins, gam56 and gam82, found in specialized
      organelles (wall-forming bodies) in the sexual stage (macrogamete) of Eimeria
      maxima are proteolytically processed into smaller glycoproteins, which are then
      incorporated into the developing oocyst wall. The identification of high
      concentrations of dityrosine and 3,4-dihydroxyphenylalanine (DOPA) in oocyst
      extracts by high-pressure liquid chromatography, together with the detection of a
      UV autofluorescence in intact oocysts, implicates dityrosine- and possibly DOPA
      protein cross-links in oocyst wall hardening. In addition, the identification of
      peroxidase activity in the wall-forming bodies of macrogametes supports the
      hypothesis that dityrosine- and DOPA-mediated cross-linking might be an enzyme
      catalyzed event. As such, the mechanism of oocyst wall formation in Eimeria, is
      analogous to the underlying mechanisms involved in the stabilization of
      extracellular matrices in a number of organisms, widely distributed in nature,
      including insect resilin, nematode cuticles, yeast cell walls, mussel byssal
      threads, and sea urchin fertilization membranes.

PMID- 12796291
TI  - A gene expressed during sexual and asexual sporulation in Phytophthora infestans
      is a member of the Puf family of translational regulators.
AB  - A gene from Phytophthora infestans that was previously identified as being
      induced during the development of sexual spores was also found to be active
      during asexual sporulation. The gene, M90, was expressed as a 3.1-kb primary
      transcript containing two introns and was predicted to encode a member of the Puf
      family of translational regulators. The protein showed up to 51% amino acid
      identity to other Puf proteins within its 353-amino-acid RNA-binding domain.
      Little similarity extended beyond this region, as noted for other members of the
      family. Expression of M90 was measured by using RNA blots and transformants of P.
      infestans expressing a fusion between the M90 promoter and the beta-glucuronidase
      (GUS) gene. A 1.3-kb promoter fragment conferred the normal M90 pattern of
      expression to the GUS reporter in transformants. In matings, expression was first
      detected in male and female gametangial initials and persisted in mature
      oospores. Expression was also observed in hyphal tips just prior to asexual
      sporulation, in sporangiophores, in mature sporangia, and in zoospores. The
      signal quickly disappeared once spores made the transition to hyphae after
      germination. Nutrient limitation did not induce the gene. Potential roles for a
      translational regulator during both sexual development and asexual sporulation
      are discussed.

PMID- 12796292
TI  - RacB regulates cytoskeletal function in Dictyostelium spp.
AB  - Thus far, 14 homologues of mammalian Rac proteins have been identified in
      Dictyostelium. It is unclear whether each of these genes has a unique function or
      to what extent they play redundant roles in actin cytoskeletal organization. To
      investigate the specific function of RacB, we have conditionally expressed wild
      type (WT-RacB), dominant negative (N17-RacB), and constitutively activated (V12
      RacB) versions of the protein. On induction, cells expressing V12-RacB stopped
      growing, detached from the surface, and formed numerous spherical surface
      protrusions while cells overexpressing WT-RacB became flattened on the surface.
      In contrast, cells overexpressing N17-RacB did not show any significant
      morphological abnormalities. The surface protrusions seen in V12-RacB cells
      appear to be actin-driven protrusions because they were enriched in F-actin and
      were inhibitable by cytochalasin A treatment. The protrusions in V12-RacB cells
      did not require myosin II activity, which distinguishes them from blebs formed by
      wild-type cells under stress. Finally, we examined the functional consequences of
      expression of wild-type and mutant RacB. Phagocytosis, endocytosis, and fluid
      phase efflux rates were reduced in all cell lines expressing RacB proteins but
      the greatest decrease was observed for cells expressing V12-RacB. From these
      results, we conclude that like other members of the Rho family, RacB induces
      polymerization of actin but the consequences of activation appear to be different
      from other Dictyostelium Rac proteins so far investigated, resulting in different
      morphological and functional changes in cells.

PMID- 12796293
TI  - Expression of conventional and unconventional actins in Chlamydomonas reinhardtii
      upon deflagellation and sexual adhesion.
AB  - Chlamydomonas has two actin genes, one coding for a conventional actin and the
      other coding for a highly divergent actin. The divergent actin NAP (for "novel
      actin-like protein") is expressed only negligibly in wild-type cells but
      abundantly in a null mutant of conventional actin, the ida5 mutant. The presence
      of the dormant NAP gene suggests that NAP may also have its own function in wild
      type cells under some conditions. However, no specific functions have been
      suggested. In this study, we examined the expression of actin and NAP in wild
      type and ida5 cells under conditions where actin function has been shown to be
      important. We found that deflagellation induces the expression of NAP as well as
      that of actin in wild-type cells. The expressed NAP becomes localized to the
      regrown flagella, apparently without being associated with dynein. Mating of
      gametes also increased the expression of actin in wild-type cells and that of NAP
      in ida5 cells, resulting in accumulation of these proteins in flagella (in both
      wild-type and ida5 cells) and the fertilization tubule (only in wild-type cells).
      However, it did not induce significant NAP expression in wild-type cells. These
      and other observations suggest that the expression of actin and NAP mRNAs is
      controlled by two discrete mechanisms and that NAP plays a role in flagellar
      formation in wild-type cells.

PMID- 12796294
TI  - Pheromone-induced G2 arrest in the phytopathogenic fungus Ustilago maydis.
AB  - In the corn smut fungus Ustilago maydis, pathogenic development is initiated when
      two compatible haploid cells fuse and form the infectious dikaryon. Mating is
      dependent on pheromone recognition by compatible cells. In this report, we set
      out to evaluate the relationship between the cell cycle and the pheromone
      response in U. maydis. To achieve this, we designed a haploid pheromone
      responsive strain that is able to faithfully reproduce the native mating response
      in nutrient-rich medium. Addition of synthetic pheromone to the responsive strain
      induces the formation of mating structures, and this response is abolished by
      mutations in genes encoding components of the pheromone signal transduction
      cascade. After recognition of pheromone, U. maydis cells arrest the cell cycle in
      a postreplicative stage. Visualization of the nucleus and microtubule
      organization indicates that the arrest takes place at the G(2) phase. Chemical
      induced cell cycle arrest and release in the presence of pheromone further
      support this conclusion.

PMID- 12796295
TI  - The intestinal protozoan parasite Entamoeba histolytica contains 20 cysteine
      protease genes, of which only a small subset is expressed during in vitro
      cultivation.
AB  - Cysteine proteases are known to be important pathogenicity factors of the
      protozoan parasite Entamoeba histolytica. So far, a total of eight genes coding
      for cysteine proteases have been identified in E. histolytica, two of which are
      absent in the closely related nonpathogenic species E. dispar. However, present
      knowledge is restricted to enzymes expressed during in vitro cultivation of the
      parasite, which might represent only a subset of the entire repertoire. Taking
      advantage of the current E. histolytica genome-sequencing efforts, we analyzed
      databases containing more than 99% of all ameba gene sequences for the presence
      of cysteine protease genes. A total of 20 full-length genes was identified
      (including all eight genes previously reported), which show 10 to 86% sequence
      identity. The various genes obviously originated from two separate ancestors
      since they form two distinct clades. Despite cathepsin B-like substrate
      specificities, all of the ameba polypeptides are structurally related to
      cathepsin L-like enzymes. None of the previously described enzymes but 7 of the
      12 newly identified proteins are unique compared to cathepsins of higher
      eukaryotes in that they are predicted to have transmembrane or
      glycosylphosphatidylinositol anchor attachment domains. Southern blot analysis
      revealed that orthologous sequences for all of the newly identified proteases are
      present in E. dispar. Interestingly, the majority of the various cysteine
      protease genes are not expressed in E. histolytica or E. dispar trophozoites
      during in vitro cultivation. Therefore, it is likely that at least some of these
      enzymes are required for infection of the human host and/or for completion of the
      parasite life cycle.

PMID- 12796296
TI  - Scw1p antagonizes the septation initiation network to regulate septum formation
      and cell separation in the fission yeast Schizosaccharomyces pombe.
AB  - Cytokinesis in the fission yeast Schizosaccharomyces pombe is regulated by a
      signaling pathway termed the septation initiation network (SIN). The SIN is
      essential for initiation of actomyosin ring constriction and septum formation. In
      a screen to search for mutations that can rescue the sid2-250 SIN mutant, we
      obtained scw1-18. Both the scw1-18 mutant and the scw1 deletion mutant (scw1Delta
      mutant), have defects in cell separation. Both the scw1-18 and scw1Delta
      mutations rescue the growth defects of not just the sid2-250 mutant but also the
      other temperature-sensitive SIN mutants. Other cytokinesis mutants, such as those
      defective for actomyosin ring formation, are not rescued by scw1Delta. scw1Delta
      does not seem to rescue the SIN by restoring SIN signaling defects. However,
      scw1Delta may function downstream of the SIN to promote septum formation, since
      scw1Delta can rescue the septum formation defects of the cps1-191beta-1,3-glucan
      synthase mutant, which is required for synthesis of the primary septum.

PMID- 12796297
TI  - Novel Rho GTPase involved in cytokinesis and cell wall integrity in the fission
      yeast Schizosaccharomyces pombe.
AB  - The Rho family of GTPases is present in all eukaryotic cells from yeast to
      mammals; they are regulators in signaling pathways that control actin
      organization and morphogenetic processes. In yeast, Rho GTPases are implicated in
      cell polarity processes and cell wall biosynthesis. It is known that Rho1 and
      Rho2 are key proteins in the construction of the cell wall, an essential
      structure that in Schizosaccharomyces pombe is composed of beta-glucan, alpha
      glucan, and mannoproteins. Rho1 regulates the synthesis of 1,3-beta-D-glucan by
      activation of the 1,3-beta-D-glucan synthase, and Rho2 regulates the synthesis of
      alpha-glucan by the 1,3-alpha-D-glucan synthase Mok1. Here we describe the
      characterization of another Rho GTPase in fission yeast, Rho4. rho4Delta cells
      are viable but display cell separation defects at high temperature. In agreement
      with this observation, Rho4 localizes to the septum. Overexpression of rho4(+)
      causes lysis and morphological defects. Several lines of evidence indicate that
      both rho4(+) deletion or rho4(+) overexpression result in a defective cell wall,
      suggesting an additional role for Rho4 in cell wall integrity. Rho4Delta cells
      also accumulate secretory vesicles around the septum and are defective in actin
      polarization. We propose that Rho4 could be involved in the regulation of the
      septum degradation during cytokinesis.

PMID- 12796298
TI  - A Saccharomyces cerevisiae mutant unable to convert glucose to glucose-6
      phosphate accumulates excessive glucose in the endoplasmic reticulum due to core
      oligosaccharide trimming.
AB  - D-Glucose is the preferred carbon and energy source for most eukaryotic cells.
      Immediately following its uptake, glucose is rapidly phosphorylated to glucose-6
      phosphate (Glc-6-P). The yeast Saccharomyces cerevisiae has three enzymes (Hxk1p,
      Hxk2p, and Glk1p) that convert glucose to Glc-6-P. In the present study, we found
      that yeast mutants lacking any two of these enzymes retain the ability to
      efficiently convert glucose to Glc-6-P and thus maintain a low level of cellular
      glucose. However, a mutant strain lacking all three glucose-phosphorylating
      enzymes contained up to 225-fold more intracellular glucose than normal. Drugs
      that inhibit the synthesis or the trimming of the lipid-linked core
      oligosaccharide Glu(3)Man(9)GlcNac(2) effectively reduced the accumulation of
      glucose. Similarly, mutations that block the addition of glucose residues to the
      core oligosaccharide moiety, such as alg5Delta or alg6Delta, also diminished
      glucose accumulation. These results indicate that the intracellular glucose
      accumulation observed in the glucose phosphorylation mutant results primarily
      from the trimming of glucose residues from core oligosaccharide chains within the
      endoplasmic reticulum (ER). Consistent with this conclusion, both [(14)C]glucose
      exchange and subcellular fractionation experiments indicate that much of the
      accumulated glucose is retained within an intracellular compartment, suggesting
      that the efficient transport of glucose from the ER to the cytosol in yeast may
      be coupled to its rephosphorylation to Glc-6-P. The high level of cellular
      glucose was associated with an increased level of protein glycation and the
      release of glucose into the culture medium via its transit through the secretory
      pathway. Finally, we also found that the accumulation of glucose may lead to a
      subtle alteration in ion homeostasis, particularly Ca(2+) uptake. This suggests
      that this mutant strain may serve as a useful model to study the consequences of
      excessive glucose accumulation and protein glycation.

PMID- 12796299
TI  - RNA polymerase I transcribes procyclin genes and variant surface glycoprotein
      gene expression sites in Trypanosoma brucei.
AB  - In eukaryotes, RNA polymerase (pol) I exclusively transcribes the large rRNA gene
      unit (rDNA) and mRNA is synthesized by RNA pol II. The African trypanosome,
      Trypanosoma brucei, represents an exception to this rule. In this organism,
      transcription of genes encoding the variant surface glycoprotein (VSG) and the
      procyclins is resistant to alpha-amanitin, indicating that it is mediated by RNA
      pol I, while other protein-coding genes are transcribed by RNA pol II. To obtain
      firm proof for this concept, we generated a T. brucei cell line which exclusively
      expresses protein C epitope-tagged RNA pol I. Using an anti-protein C
      immunoaffinity matrix, we specifically depleted RNA pol I from transcriptionally
      active cell extracts. The depletion of RNA pol I impaired in vitro transcription
      initiated at the rDNA promoter, the GPEET procyclin gene promoter, and a VSG gene
      expression site promoter but did not affect transcription from the spliced leader
      (SL) RNA gene promoter. Fittingly, induction of RNA interference against the RNA
      pol I largest subunit in insect-form trypanosomes significantly reduced the
      relative transcriptional efficiency of rDNA, procyclin genes, and VSG expression
      sites in vivo whereas that of SL RNA, alphabeta-tubulin, and heat shock protein
      70 genes was not affected. Our studies unequivocally show that T. brucei harbors
      a multifunctional RNA pol I which, in addition to transcribing rDNA, transcribes
      procyclin genes and VSG gene expression sites.

PMID- 12796300
TI  - Rapamycin treatment results in GATA factor-independent hyperphosphorylation of
      the proline utilization pathway activator in Saccharomyces cerevisiae.
AB  - Treatment of Saccharomyces cerevisiae cells with the immunosuppressive drug
      rapamycin results in a variety of cellular changes in response to perceived
      nutrient deprivation. Among other effects, rapamycin treatment results in the
      nuclear localization of the global nitrogen activators Gln3p and Nil1p/Gat1p,
      which leads to expression of nitrogen assimilation genes. The proline utilization
      (Put) pathway genes were shown to be among the genes induced by rapamycin. Having
      previously shown that the Put pathway activator Put3p is differentially
      phosphorylated in response to the quality of the nitrogen source, we examined the
      phosphorylation status of Put3p after rapamycin treatment. Treatment with
      rapamycin resulted in the hyperphosphorylation of Put3p, which was independent of
      Gln3p, Nil1p, and Ure2p. The relative contributions of global nitrogen (Gln3p and
      Nil1p) and pathway-specific (Put3p) activators to rapamycin-induced expression of
      the target gene PUT1 were also examined. We found that Nil1p and Put3p, but not
      Gln3p, play major roles in rapamycin-induced PUT1 expression. Our findings show
      that perceived nitrogen deprivation triggered by rapamycin treatment and steady
      state growth in nitrogen-derepressing conditions are associated with
      hyperphosphorylation of Put3p and increased PUT1 expression. Rapamycin treatment
      and nitrogen derepression may share some, but not all, regulatory elements, since
      Gln3p and Nil1p do not participate identically in both processes and are not
      required for hyperphosphorylation. A complex relationship exists among the global
      and pathway-specific regulators, depending on the nature and quality of the
      nitrogen source.

PMID- 12796301
TI  - RBP38, a novel RNA-binding protein from trypanosomatid mitochondria, modulates
      RNA stability.
AB  - We describe here the isolation and characterization of a novel RNA-binding
      protein, RBP38, from Leishmania tarentolae mitochondria. This protein does not
      contain any known RNA-binding motifs and is highly conserved among the
      trypanosomatids, but no homologues were found in other organisms. Recombinant
      LtRBP38 binds single and double-stranded (ds) RNA substrates with dissociation
      constants in the 100 nM range, as determined by fluorescence polarization
      analysis. Downregulation of expression of the homologous gene, TbRBP38, in
      procyclic Trypanosoma brucei by using conditional dsRNA interference resulted in
      80% reduction of steady-state levels of RNAs transcribed from both maxicircle and
      minicircle DNA. In organello pulse-chase labeling experiments were used to
      determine the stability of RNAs in mitochondria that were depleted of TbRBP38.
      The half-life of metabolically labeled RNA decreased from approximately 160 to
      approximately 60 min after depletion. In contrast, there was no change in
      transcriptional activity. These observations suggest a role of RBP38 in
      stabilizing mitochondrial RNA.

PMID- 12796302
TI  - Dyskinetoplastic Trypanosoma brucei contains functional editing complexes.
AB  - Mitochondrial pre-mRNAs undergo posttranscriptional RNA editing as directed by
      small guide RNAs (gRNAs) to produce functional mRNAs in kinetoplastid protozoa.
      The pre-mRNAs and gRNAs are encoded in the maxicircle and minicircle components,
      respectively, of the kinetoplastid mitochondrial DNA (kDNA), and editing is
      catalyzed by a multienzyme protein complex. Trypanosoma evansi AnTat3/3, which
      lacks maxicircles but retains a single class of minicircles, and a
      dyskinetoplastic mutant of Trypanosoma brucei EATRO164, which is devoid of kDNA,
      were both shown to retain genes and proteins for the editing complex. The
      proteins are present in complexes that immunoprecipitate and sediment
      indistinguishably from wild-type complexes. The complexes catalyze precleaved
      insertion and deletion editing as well as full-round deletion editing in vitro.
      Thus, mutants which lack the natural substrates for RNA editing and all or most
      gRNAs retain editing complexes that contain the four primary catalytic activities
      of editing and function in editing, at least in vitro. Therefore neither pre-mRNA
      nor gRNA is required to form functional RNA-editing complexes.

PMID- 12796303
TI  - TbMP44 is essential for RNA editing and structural integrity of the editosome in
      Trypanosoma brucei.
AB  - RNA editing produces mature mitochondrial mRNAs in trypanosomatids by the
      insertion and deletion of uridylates. It is catalyzed by a multiprotein complex,
      the editosome. We identified TbMP44 among the components of enriched editosomes
      by a combination of mass spectrometry and DNA sequence database analysis.
      Inactivation of an ectopic TbMP44 allele in cells in which the endogenous alleles
      were disrupted abolished RNA editing, inhibited cell growth, and was eventually
      lethal to bloodstream form trypanosomes. Loss of TbMP44 mRNA was followed
      initially by a reduction in the editosome sedimentation coefficient and then by
      the absence of other editosome proteins despite the presence of the mRNA.
      Reactivation of TbMP44 gene expression resulted in the resumption of cell growth
      and the reappearance of editosomes. These data indicate that TbMP44 is a
      component of the editosome that is essential for editing and critical for the
      structural integrity of the editosome.

PMID- 12796304
TI  - A region within a lumenal loop of Saccharomyces cerevisiae Ycf1p directs
      proteolytic processing and substrate specificity.
AB  - Ycf1p, a member of the yeast multidrug resistance-associated protein (MRP)
      subfamily of ATP-binding cassette proteins, is a vacuolar membrane transporter
      that confers resistance to a variety of toxic substances such as cadmium and
      arsenite. Ycf1p undergoes a PEP4-dependent processing event to yield N- and C
      terminal cleavage products that remain associated with one another. In the
      present study, we sought to determine whether proteolytic cleavage is required
      for Ycf1p activity. We have identified a unique region within lumenal loop 6 of
      Ycf1p, designated the loop 6 insertion (L6(ins)), which appears to be necessary
      and sufficient for proteolytic cleavage, since L6(ins) can promote processing
      when moved to new locations in Ycf1p or into a related transporter, Bpt1p.
      Surprisingly, mutational results indicate that proteolytic processing is not
      essential for Ycf1p transport activity. Instead, the L6(ins) appears to regulate
      substrate specificity of Ycf1p, since certain mutations in this region lower
      cellular cadmium resistance with a concomitant gain in arsenite resistance.
      Although some of these L6(ins) mutations block processing, there is no
      correlation between processing and substrate specificity. The activity profiles
      of the Ycf1p L6(ins) mutants are dramatically affected by the strain background
      in which they are expressed, raising the possibility that another cellular
      component may functionally impact Ycf1p activity. A candidate component may be a
      new full-length MRP-type transporter (NFT1), reported in the Saccharomyces Genome
      Database as two adjacent open reading frames, YKR103w and YKR104w, but which we
      show here is present in most Saccharomyces strains as a single open reading
      frame.

PMID- 12796305
TI  - Identification of in vivo enzyme activities in the cometabolism of glucose and
      acetate by Saccharomyces cerevisiae by using 13C-labeled substrates.
AB  - A detailed characterization of the central metabolic network of Saccharomyces
      cerevisiae CEN.PK 113-7D was carried out during cometabolism of different
      mixtures of glucose and acetate, using aerobic C-limited chemostats in which one
      of these two substrates was labeled with (13)C. To confirm the role of malic
      enzyme, an isogenic strain with the corresponding gene deleted was grown under
      the same conditions. The labeling patterns of proteinogenic amino acids were
      analyzed and used to estimate metabolic fluxes and/or make inferences about the
      in vivo activities of enzymes of the central carbon metabolism and amino acid
      biosynthesis. Malic enzyme flux increased linearly with increasing acetate
      fraction. During growth on a very-high-acetate fraction, the activity of malic
      enzyme satisfied the biosynthetic needs of pyruvate in the mitochondria, while in
      the cytosol pyruvate was supplied via pyruvate kinase. In several cases enzyme
      activities were unexpectedly detected, e.g., the glyoxylate shunt for a very-low
      acetate fraction, phosphoenolpyruvate carboxykinase for an acetate fraction of
      0.46 C-mol of acetate/C-mol of substrate, and glucose catabolism to CO(2) via the
      tricarboxylic acid cycle for a very-high-acetate fraction. Cytoplasmic alanine
      aminotransferase activity was detected, and evidence was found that alpha
      isopropylmalate synthase has two active forms in vivo, one mitochondrial and the
      other a short cytoplasmic form.

PMID- 12796306
TI  - Guanyl nucleotide exchange factor Sql2 and Ras2 regulate filamentous growth in
      Ustilago maydis.
AB  - The cyclic AMP (cAMP)-signaling pathway regulates cell morphology and plays a
      crucial role during pathogenic development of the plant-pathogenic fungus
      Ustilago maydis. Strains lacking components of this signaling pathway, such as
      the Galpha-subunit Gpa3 or the adenylyl cyclase Uac1, are nonpathogenic and grow
      filamentously. On the other hand, strains exhibiting an activated cAMP pathway
      due to a dominant-active allele of gpa3 display a glossy colony phenotype and are
      unable to proliferate in plant tumors. Here we present the identification of sql2
      as a suppressor of the glossy colony phenotype of a gpa3(Q206L) strain. sql2
      encodes a protein with similarity to CDC25-like guanine nucleotide exchange
      factors, which are known to act on Ras proteins. Overexpression of sql2 leads to
      filamentous growth that cannot be suppressed by exogenous cAMP, suggesting that
      Sql2 does not act upstream of Uac1. To gain more insight in signaling processes
      regulated by Sql2, we isolated two genes encoding Ras proteins. Expression of
      dominant active alleles of ras1 and ras2 showed that Ras2 induces filamentous
      growth while Ras1 does not affect cell morphology but elevates pheromone gene
      expression. These results indicate that Ras1 and Ras2 fulfill different functions
      in U. maydis. Moreover, observed similarities between the filaments induced by
      sql2 and ras2 suggest that Sql2 is an activator of Ras2. Interestingly, sql2
      deletion mutants are affected in pathogenic development but not in mating,
      indicating a specific function of sql2 during pathogenesis.

PMID- 12796307
TI  - Genetic interactions of the E3 ubiquitin ligase component FbxA with cyclic AMP
      metabolism and a histidine kinase signaling pathway during Dictyostelium
      discoideum development.
AB  - Dictyostelium discoideum amoebae with an altered fbxA gene, which is thought to
      encode a component of an SCF E3 ubiquitin ligase, have defective regulation of
      cell type proportionality. In chimeras with wild-type cells, the mutant amoebae
      form mainly spores, leaving the construction of stalks to wild-type cells. To
      examine the role of fbxA and regulated proteolysis, we have recovered the
      promoter of fbxA and shown that it is expressed in a pattern resembling that of a
      prestalk-specific gene until late in development, when it is also expressed in
      developing spore cells. Because fbxA cells are developmentally deficient in pure
      culture, we were able to select suppressor mutations that promote sporulation of
      the original mutant. One suppressor mutation resides within the gene regA, which
      encodes a cyclic AMP (cAMP) phosphodiesterase linked to an activating response
      regulator domain. In another suppressor, there has been a disruption of dhkA, a
      gene encoding a two-component histidine kinase known to influence Dictyostelium
      development. RegA appears precociously and in greater amounts in the fbxA mutant
      than in the wild type, but in an fbxA/dhkA double mutant, RegA is restored to
      wild-type levels. Because the basis of regA suppression might involve alterations
      in cAMP levels during development, the concentrations of cAMP in all strains were
      determined. The levels of cAMP are relatively constant during multicellular
      development in all strains except the dhkA mutant, in which it is reduced at
      least sixfold. The level of cAMP in the double mutant dhkA/fbxA is relatively
      normal. The levels of cAMP in the various mutants do not correlate with spore
      formation, as would be expected on the basis of our present understanding of the
      signaling pathway leading to the induction of spores. Altered amounts of RegA and
      cAMP early in the development of the mutants suggest that both fbxA and dhkA
      genes act earlier than previously thought.

PMID- 12796308
TI  - Changing patterns of gene expression in dictyostelium prestalk cell subtypes
      recognized by in situ hybridization with genes from microarray analyses.
AB  - We used microarrays carrying most of the genes that are developmentally regulated
      in Dictyostelium to discover those that are preferentially expressed in prestalk
      cells. Prestalk cells are localized at the front of slugs and play crucial roles
      in morphogenesis and slug migration. Using whole-mount in situ hybridization, we
      were able to verify 104 prestalk genes. Three of these were found to be expressed
      only in cells at the very front of slugs, the PstA cell type. Another 10 genes
      were found to be expressed in the small number of cells that form a central core
      at the anterior, the PstAB cell type. The rest of the prestalk-specific genes are
      expressed in PstO cells, which are found immediately posterior to PstA cells but
      anterior to 80% of the slug that consists of prespore cells. Half of these are
      also expressed in PstA cells. At later stages of development, the patterns of
      expression of a considerable number of these prestalk genes changes
      significantly, allowing us to further subdivide them. Some are expressed at much
      higher levels during culmination, while others are repressed. These results
      demonstrate the extremely dynamic nature of cell-type-specific expression in
      Dictyostelium and further define the changing physiology of the cell types. One
      of the signals that affect gene expression in PstO cells is the hexaphenone DIF
      1. We found that expression of about half of the PstO-specific genes were
      affected in a mutant that is unable to synthesize DIF-1, while the rest appeared
      to be DIF independent. These results indicate that differentiation of some
      aspects of PstO cells can occur in the absence of DIF-1.

PMID- 12796309
TI  - MFE1, a member of the peroxisomal hydroxyacyl coenzyme A dehydrogenase family,
      affects fatty acid metabolism necessary for morphogenesis in Dictyostelium spp.
AB  - Beta-oxidation of long-chain fatty acids and branched-chain fatty acids is
      carried out in mammalian peroxisomes by a multifunctional enzyme (MFE) or D
      bifunctional protein, with separate domains for hydroxyacyl coenzyme A (CoA)
      dehydrogenase, enoyl-CoA hydratase, and steroid carrier protein SCP2. We have
      found that Dictyostelium has a gene, mfeA, encoding MFE1 with homology to the
      hydroxyacyl-CoA dehydrogenase and SCP2 domains. A separate gene, mfeB, encodes
      MFE2 with homology to the enoyl-CoA hydratase domain. When grown on a diet of
      bacteria, Dictyostelium cells in which mfeA is disrupted accumulate excess
      cyclopropane fatty acids and are unable to develop beyond early aggregation.
      Axenically grown mutant cells, however, developed into normal fruiting bodies
      composed of spores and stalk cells. Comparative analysis of whole-cell lipid
      compositions revealed that bacterially grown mutant cells accumulated
      cyclopropane fatty acids that remained throughout the developmental stages. Such
      a persistent accumulation was not detected in wild-type cells or axenically grown
      mutant cells. Bacterial phosphatidylethanolamine that contains abundant
      cyclopropane fatty acids inhibited the development of even axenically grown
      mutant cells, while dipalmitoyl phosphatidylethanolamine did not. These results
      suggest that MFE1 protects the cells from the increase of the harmful xenobiotic
      fatty acids incorporated from their diets and optimizes cellular lipid
      composition for proper development. Hence, we propose that this enzyme plays an
      irreplaceable role in the survival strategy of Dictyostelium cells to form spores
      for their efficient dispersal in nature.

PMID- 12796312
TI  - Censoring science.

PMID- 12796310
TI  - Histone-like proteins of the dinoflagellate Crypthecodinium cohnii have
      homologies to bacterial DNA-binding proteins.
AB  - The dinoflagellates have very large genomes encoded in permanently condensed and
      histoneless chromosomes. Sequence alignment identified significant similarity
      between the dinoflagellate chromosomal histone-like proteins of Crypthecodinium
      cohnii (HCCs) and the bacterial DNA-binding and the eukaryotic histone H1
      proteins. Phylogenetic analysis also supports the origin of the HCCs from histone
      like proteins of bacteria.

PMID- 12796311
TI  - Evidence that synthesis of the Saccharomyces cerevisiae mitochondrially encoded
      ribosomal protein Var1p may be membrane localized.
AB  - The 5'-untranslated leaders of mitochondrial mRNAs appear to localize translation
      within the organelle. VAR1 is the only yeast mitochondrial gene encoding a major
      soluble protein. A chimeric mRNA bearing the VAR1 untranslated regions and the
      coding sequence for pre-Cox2p appears to be translated at the inner membrane
      surface. We propose that translation of the ribosomal protein Var1p is also
      likely to occur in close proximity to the inner membrane.

PMID- 12796315
TI  - Reporting HIV infection.

PMID- 12796316
TI  - Antiepileptic drugs in pregnancy.

PMID- 12796318
TI  - A tip for surgeons.

PMID- 12796319
TI  - Compassionate care.

PMID- 12796320
TI  - The perils of PDAs.

PMID- 12796321
TI  - The best protection.

PMID- 12796325
TI  - Investigating CAM.

PMID- 12796322
TI  - The perils of PDAs.

PMID- 12796326
TI  - Should cost-effectiveness take the blame?

PMID- 12796328
TI  - CMAJ on the Web.

PMID- 12796330
TI  - Relative risks or odds ratios?

PMID- 12796331
TI  - Effects of low income on infant health.
AB  - BACKGROUND: Few population-based studies have analyzed the link between poverty
      and infant morbidity. In this study, we wanted to determine whether inadequate
      income itself has an impact on infant health. METHODS: We interviewed 2223
      mothers of 5-month-old children participating in the 1998 phase of the Quebec
      Longitudinal Study of Child Development to determine their infant's health and
      the sociodemographic characteristics of the household (including household
      income, breast-feeding and the smoking habits of the mother). Data on the health
      of the infants at birth were taken from medical records. We examined the effects
      of household income using Statistics Canada definitions of sufficient (above the
      low-income threshold), moderately inadequate (between 60% and 99% of the low
      income threshold) and inadequate (below 60% of the low-income threshold) income
      on the mother's assessment of her child's overall health, her report of her
      infant's chronic health problems and her report of the number of times, if any,
      her child had been admitted to hospital since birth. In the analysis, we
      controlled for factors known to affect infant health: infant characteristics and
      neonatal health problems, the mother's level of education, the presence or
      absence of a partner, the duration of breast-feeding and the mother's smoking
      status. RESULTS: Compared with infants in households with sufficient incomes,
      those in households with lower incomes were more likely to be judged by their
      mothers to be in less than excellent health (moderately inadequate incomes:
      adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.1; very
      inadequate incomes: adjusted OR 1.8, 95% CI 1.3-2.6). Infants in households with
      moderately inadequate incomes were more likely to have been admitted to hospital
      (adjusted OR 1.8, 95% CI 1.2-2.6) than those in households with sufficient
      incomes, but the same was not true of infants in households with very inadequate
      incomes (adjusted OR 0.7, 95% CI 0.4-1.2). Household income did not significantly
      affect the likelihood of an infant having chronic health problems.
      INTERPRETATION: Less than sufficient household incomes are associated with poorer
      overall health and higher hospital admission rates among infants in the first 5
      months of life, even after adjustment for factors known to affect infant health,
      including the mother's level of education.

PMID- 12796332
TI  - Iron poisoning in young children: association with the birth of a sibling.
AB  - BACKGROUND: Iron is a leading cause of death due to poisoning in young children.
      Because perinatal iron therapy is common, the presence of these tablets, which
      have a candylike appearence, in the home may pose a hazard to a mother's other
      young children. We explored the association between iron poisoning in young
      children and the birth of a sibling. METHODS: We conducted a population-based
      case-control study linking health care databases in Ontario. Health care records
      for the mothers of children less than 3 years of age admitted to hospital with
      iron poisoning between Apr. 1, 1991, and Mar. 31, 2000, were compared with those
      for the mothers of age- and sex-matched control children without iron poisoning.
      RESULTS: We studied records for 40 children admitted to hospital for iron
      poisoning. Seventeen cases (42%) occurred within a year (before or after) a
      sibling's birth. Children whose mothers had given birth to a sibling were almost
      twice as likely as children whose mothers had not given birth to a sibling to be
      admitted for iron poisoning within 6 months of birth (adjusted odds ratio [OR]
      1.9, 95% confidence interval [CI] 0.9 to 3.9). The postpartum year was associated
      with a consistently elevated risk, including an almost 4-fold increase in the
      risk of iron poisoning during the first postpartum month (adjusted OR 3.6, 95% CI
      0.8 to 16.5). INTERPRETATION: Pregnancy is a major risk factor for iron poisoning
      in young children, and the period immediately after delivery is associated with
      the greatest risk. Almost half of all hospital admissions for iron poisoning in
      young children could be prevented by keeping iron supplements safely out of reach
      in the year before and after the birth of a sibling.

PMID- 12796333
TI  - Requirements for physicians in 2030: why population aging matters less than you
      may think.

PMID- 12796334
TI  - Preparing emergency physicians for the future.

PMID- 12796335
TI  - Emergency medicine practice and training in Canada.

PMID- 12796336
TI  - Nephrology: 4. Strategies for the care of adults with chronic kidney disease.

PMID- 12796337
TI  - Guidelines for the investigation and follow-up of individuals under medical
      surveillance for tuberculosis after arriving in Canada: a summary.

PMID- 12796338
TI  - Updated SARS case definition using laboratory criteria.

PMID- 12796339
TI  - Incidental, delayed diagnosis of gastric foreign body in a 15-year-old boy.

PMID- 12796341
TI  - Should severely injured legs be saved or amputated?

PMID- 12796348
TI  - Taking a stand in Timmins: quit smoking, or forgo surgery.

PMID- 12796349
TI  - Quebec tackles electroconvulsive therapy issue.

PMID- 12796350
TI  - Australia's MDs decry poor state of Aboriginal health.

PMID- 12796351
TI  - What's keeping our FPs busy?

PMID- 12796352
TI  - Will arbitration settlement aid MD retention in Newfoundland?

PMID- 12796354
TI  - Sugar industry sour on WHO report.

PMID- 12796356
TI  - Soft tissue sarcomas of adults: state of the translational science.
AB  - Sarcomas--like leukemias, which are also mesodermal malignancies--carry
      biological significance disproportionate to their clinical frequency.
      Identification of mutations and translocations associated with these tumors has
      illuminated aberrant signaling pathways that cause these diseases, determine
      their behavior, and are therapeutic targets. Activated receptor-associated
      tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has
      proven a clinically effective target for enzyme inhibition. A translocation
      involving a single gene family, consisting of EWS and related genes, has been
      identified in five different sarcomas, and its chimeric protein products could
      prove similarly amenable to inhibitors. Resolution of the histopathological
      complexity is being aided by data from molecular and chromosomal
      characterization. Improvements in imaging, definition of prognostic factors, and
      surgical and radiotherapeutic treatment have resulted in improved local control.
      Continued progress will depend on further adapting the rapidly evolving
      technologies of genomics and proteomics. It will also depend upon accurate
      histopathological diagnosis based on validated reagents and consistent
      methodologies applied to adequate tissue samples derived from patients with
      complete clinical data. Finally, multicenter, coordinated trials, such as those
      that occurred with assessment of imatinib mesylate in metastatic gastrointestinal
      stromal tumors, will assure the most rapid reductions in morbidity and mortality.

PMID- 12796357
TI  - Tumor response to ionizing radiation combined with antiangiogenesis or vascular
      targeting agents: exploring mechanisms of interaction.
AB  - Recent preclinical studies have suggested that radiotherapy in combination with
      antiangiogenic/vasculature targeting agents enhances the therapeutic ratio of
      ionizing radiation alone. Because radiotherapy is one of the most widely used
      treatments for cancer, it is important to understand how best to use these two
      modalities to aid in the design of rational patient protocols. The mechanisms of
      interaction between antiangiogenic/vasculature targeting agents and ionizing
      radiation are complex and involve interactions between the tumor stroma and
      vasculature and the tumor cells themselves. Vascular targeting agents are aimed
      specifically at the existing tumor vasculature. Antiangiogenic agents target
      angiogenesis or the new growth of tumor vessels. These agents can decrease
      overall tumor resistance to radiation by affecting both tumor cells and tumor
      vasculature, thereby breaking the codependent cycle of tumor growth and
      angiogenesis. The hypoxic microenvironment of the tumor also contributes to the
      mechanisms of interactions between antiangiogenic/vasculature targeting agents
      and ionizing radiation. Hypoxia stimulates up-regulation of angiogenic and tumor
      cell survival factors, giving rise to tumor proliferation, radioresistance, and
      angiogenesis. Preclinical evidence suggests that antiangiogenic agents reduce
      tumor hypoxia and provides a rationale for combining these agents with ionizing
      radiation. Optimal scheduling of combined treatment with these agents and
      ionizing radiation will ultimately depend on understanding how tumor oxygenation
      changes as tumors regress and regrow during exposure to these agents. This review
      article explores the complex interactions between antiangiogenic/vasculature
      targeting agents and radiation and offers insight into the mechanisms of
      interaction that may be responsible for improved tumor response to radiation.

PMID- 12796358
TI  - Approval summary: imatinib mesylate capsules for treatment of adult patients with
      newly diagnosed philadelphia chromosome-positive chronic myelogenous leukemia in
      chronic phase.
AB  - PURPOSE: The purpose is to describe the Food and Drug Administration (FDA) review
      and approval of imatinib (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ)
      for treatment of adult patients with newly diagnosed Philadelphia chromosome
      positive chronic myelogenous leukemia (CML) in chronic phase. EXPERIMENTAL
      DESIGN: The FDA reviewed data in electronic format from a randomized controlled
      clinical trial of 1106 adult patients with newly diagnosed Philadelphia
      chromosome-positive CML in chronic phase, comparing imatinib with the combination
      of IFN-alpha and cytarabine. RESULTS: Imatinib showed clinically and
      statistically significantly better results for time-to-progression to accelerated
      phase or blast crisis, progression-free survival, complete hematological response
      rate, and cytogenetic response rate. With a median follow-up of 14 months, a
      maximum follow-up of 19.5 months, and an expected median survival of 5-6 years on
      the IFN-alpha/cytarabine control arm, few of the expected progressions to
      accelerated or blast phase or deaths have occurred. Imatinib was also better
      tolerated. Edema, nausea, rigors, neutropenia, and headache were more frequent in
      women. Only 57% of the IFN-alpha target dose was administered, and only 68% of
      patients received any cytarabine. However, this does not appear to adequately
      explain the superiority of imatinib observed in this trial. Results of a
      population pharmacokinetic study in a subgroup of 371 patients and a separate
      rifampin-imatinib drug-drug interaction study in healthy volunteers are
      presented. CONCLUSIONS: On December 20, 2002, imatinib was granted accelerated
      approval under subpart H, rather than regular approval. Follow-up is short
      compared with the natural history of chronic phase CML or more mature results
      with established therapies such as IFN-alpha or transplantation. If imatinib
      should stop working after 1.5-2 years, the results could be importantly different
      from the present analysis. As a Phase IV postmarketing commitment, the applicant
      has agreed to provide follow-up reports on this imatinib study annually for the
      next 6 years.

PMID- 12796359
TI  - The estrogen receptor: a model for molecular medicine.
AB  - The identification of the estrogen receptor (ER) in the laboratory provided a
      mechanism to describe the target site specificity of estrogen action in uterus,
      vagina, pituitary gland, and breast cancer. Most importantly, a test was
      established to predict the outcome of antihormonal therapy in breast cancer, and
      a target was identified to develop new drugs for the treatment and prevention of
      breast cancer. The development of tamoxifen for the treatment of all stages of ER
      positive breast cancers has resulted in the improved survival of breast cancer
      patients. However, the recognition of selective ER modulation, i.e., estrogen
      like action in bones and lowering circulating cholesterol but antiestrogenic
      actions in breast and uterus, has resulted in the development of multifunctional
      medicines with the goal of preventing not only breast and uterine cancer but also
      osteoporosis and coronary heart disease.

PMID- 12796360
TI  - Is there a role for the assessment of health-related quality of life in the
      clinical evaluation of novel cytostatic agents?: Commentary re: P. M. LoRusso,
      Improvements in quality of life and disease-related symptoms in phase I trials of
      the selective oral epidermal growth factor receptor tyrosine kinase inhibitor
      ZD1839 in non-small cell lung cancer and other solid tumors. Clin. Cancer Res.,
      9: 2040-2048, 2003.

PMID- 12796361
TI  - Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor
      prognosis and identification of PPM1D and APPBP2 as likely amplification targets.
AB  - PURPOSE: Although tumor stage is considered a prognosticfeature for ovarian clear
      cell adenocarcinomas (OCCAs), it is not likely to fully account for the clinical
      and biological variability characteristic of the disease. The aim of this study
      was to investigate aberrations of DNA copy number in OCCA tumors and identify
      genetic markers that would increase our understanding of the pathogenesis of OCCA
      and assist in more accurately predicting the outcome for an individual patient
      with this disease. EXPERIMENTAL DESIGN: We determined copy number aberrations
      among 20 primary OCCA tumors by means of comparative genomic hybridization and
      investigated their relationship to clinicopathological data. We also measured
      expression levels of candidate target genes within critical regions by
      quantitative real-time reverse transcription-PCRs and compared those data with
      copy number status and patient outcomes. RESULTS: We identified several nonrandom
      chromosomal aberrations among the 20 primary OCCA tumors examined. Among them,
      gain of DNA at 17q21-q24 showed significantly negative correlation with disease
      free and overall survival (P = 0.0012 and 0.0039, respectively, log-rank test).
      This correlation held even for patients with stage I tumors. Among 15 candidate
      genes within the 17q21-q24 region, we found significantly elevated expression of
      PPM1D and APPBP2, and their heightened expression correlated negatively with
      disease-free survival (P = 0.0090, log-rank test adjusted for multiple
      comparisons). CONCLUSIONS: Information gained from our relatively large panel of
      OCCA tumors suggested that 17q21-q24 gain and consequent overexpression of two
      potential targets, PPM1D and APPBP2, are associated with malignant phenotypes of
      this tumor and may be useful predictors for prognosis.

PMID- 12796362
TI  - Two molecular subgroups of Wilms' tumors with or without WT1 mutations.
AB  - PURPOSE: Wilms' tumors (WTs) exhibit more than one pattern of differentiation,
      each of which is associated with distinctive clinical features and treatment
      responses. Mutations in the WT1 gene are found predominantly in WTs with stromal
      histology. To better understand the biological and clinical features in different
      WTs, we have analyzed WTs with and without WT1 mutations for a set of parameters.
      EXPERIMENTAL DESIGN: Twenty-two new WTs were analyzed for WT1 mutations by PCR
      single-strand conformational polymorphism. Five tumors with WT1 mutations and six
      tumors without WT1 mutations were studied for the presence of WT1 transcripts and
      protein as well as for the expression of differentiation markers. RESULTS: Two
      new WT1 mutations were identified in stromal-predominant tumors, and none were
      identified in the other histological subtypes. Tumors with WT1 mutations
      expressed mutant messages, cytoplasmic truncated WT1 proteins, and muscle
      markers. In contrast, blastemal-predominant tumors without mutations showed
      nuclear WT1 protein staining. Both tumor types were positive for markers of early
      induced mesenchyme and one marker of uninduced mesenchyme, but blastemal
      predominant tumors also expressed cytokeratin, suggesting that these are further
      along the epithelial differentiation pathway. CONCLUSIONS: Our data show that the
      two-hit inactivation of WT1 is operative in stromal-predominant WTs. Cells
      without functional nuclear WT1 protein start a faulty differentiation program. In
      contrast, blastemal-predominant tumors express wild-type WT1 and show early signs
      of epithelialization. The extensive rhabdomyomatous differentiation and the
      presence of WT1 mutations may be used as a diagnostic tool to identify a tumor
      subtype that seems to respond poorly to chemotherapy. These studies provide a
      foundation for improvement in tumor classification and ultimately for the
      development of more individualized tumor treatments.

PMID- 12796363
TI  - Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor
      expression in MKN 28 gastric cells through an epidermal growth factor receptor-,
      cyclooxygenase-2-dependent mechanism.
AB  - PURPOSE: Helicobacter pylori causes gastric damage and is involved in gastric
      carcinogenesis. Vascular endothelial growth factor (VEGF) plays a major role in
      gastric mucosa repair and is overexpressed in gastric cancer. We investigated:
      (a) whether H. pylori, and in particular H. pylori VacA toxin, affected VEGF
      expression in gastric epithelial cells in culture; and (b) the signal
      transduction pathway involved in any effect exerted by H. pylori. EXPERIMENTAL
      DESIGN: MKN-28 cells were incubated with uninoculated BCF (control) or with BCF
      obtained from VacA-producing wild-type H. pylori 60190 strain or from its
      isogenic mutant 60190:v1, specifically lacking vacA gene in the presence or
      absence of ZD 1839, a selective inhibitor of the epidermal growth factor receptor
      (EGFR) tyrosine kinase, PD098059, a selective inhibitor of mitogen-activated
      protein (MAP)/extracellular signal-regulated kinase (ERK) kinase, the kinase
      responsible for ERK phosphorylation, or SC-236, a selective inhibitor of
      cyclooxygenase (COX)-2 for 24-48 h. RESULTS: (a) Toxigenic H. pylori up-regulated
      VEGF mRNA and protein expression and caused a 2.5-fold increase in VEGF release
      compared with control, whereas nontoxigenic H. pylori did not; (b) H. pylori VacA
      toxin-induced up-regulation of VEGF was counteracted by selective inhibition of
      EGFR tyrosine kinase; (c) toxigenic H. pylori activated the ERK/MAP kinase
      cascade, and inhibition of MAP kinase activation counteracted H. pylori-induced
      VEGF up-regulation; (d) toxigenic H. pylori up-regulated COX-2 expression, and
      this effect was counteracted by blockade of EGFR tyrosine kinase; and (e) COX-2
      selective inhibition counteracted H. pylori-induced up-regulation of VEGF.
      CONCLUSION: (a) H. pylori up-regulates VEGF expression in gastric epithelial
      cells; and (b) this effect is specifically related to VacA toxin and seems to
      depend on the activation of an EGFR-, MAP kinase-, and COX-2-mediated pathway.

PMID- 12796364
TI  - Gene expression profiling and functional activity of human dendritic cells
      induced with IFN-alpha-2b: implications for cancer immunotherapy.
AB  - PURPOSE: In this study, we have compared patterns of gene expression and
      functional activity of human dendritic cells (DCs) cultured under defined
      conditions in IFN-alpha-2b and recombinant human granulocyte macrophage colony
      stimulating factor (DCA) with cells grown in granulocyte macrophage colony
      stimulating factor and IL-4 (DC4) as an initial step in evaluating the clinical
      utility of DCA in cancer immunotherapy. EXPERIMENTAL DESIGN AND RESULTS:
      Comparison of mRNA transcript profiles between DCA and DC4 revealed different
      expression patterns for cytokines, chemokines, chemokine receptors, costimulatory
      molecules, and adhesion proteins. Many genes involved in antigen (Ag) processing
      were equally expressed in both populations; however, expression of transcripts
      involved in Ag presentation was increased in DCA. DCA also showed up-regulation
      of Toll-like receptor 2 and 3, as well as several tumor necrosis factor family
      ligands. Consistent with expression profiling, functional assays demonstrated
      that DCAs were more potent stimulators of naive T-cell responses than DC4 in an
      interleukin 15 and interleukin 1beta-dependent manner. DCA-mediated tumor cell
      directed cytotoxicity induced apoptosis in different human tumor cell lines and
      internalized apoptotic bodies to a greater extent than DC4. Lastly, in vitro
      priming experiments, using apoptotic cells or peptide as sources of Ag, showed
      that DCA drove the expansion of tumor peptide Ag-specific autologous CD8+ T cells
      to a greater extent than DC4. CONCLUSIONS: The unique phenotype conferred by
      culturing DCs in IFN-alpha-2b may be useful in adoptive transfer regimens where
      the destruction of tumor cells in situ, initiation of T-cell responses toward
      tumor tissue with unknown Ags, and/or enhancement of pre-existing Ag-specific
      memory responses are desired outcomes.

PMID- 12796365
TI  - Phase I trial and pharmacokinetics of fenretinide in children with neuroblastoma.
AB  - PURPOSE: Fenretinide (4HPR), a synthetic retinoid, induces apoptosis in
      neuroblastoma cells. A Phase I study in children with neuroblastoma was designed
      to determine maximum tolerated dose, toxicity, and pharmacokinetics. EXPERIMENTAL
      DESIGN: Fifty-four patients received oral 4HPR, once daily, for 28 days, followed
      by a 7-day interruption, for up to 6 courses. The starting dose was 100
      mg/m(2)/day. At least 3 patients were entered at each escalating 4HPR dose level.
      Pharmacokinetic sampling was performed on days 1 and 28 of the first course.
      RESULTS: Fifty-four patients, of whom 53 were evaluable, received doses between
      100 and 4000 mg/m(2)/day for a total of 168 courses. Additional dose escalation
      was precluded by capsule number intake. A total of 34 of 53 evaluable patients
      showed manageable, reversible toxicities, which were not dose related. One dose
      limiting toxicity (nyctalopia grade 3) occurred after the 1000 mg/m(2)/day dose.
      Twelve patients showed grade 2 toxicity: skin xerosis (6 cases); nyctalopia (3
      cases); hepatic toxicity (1 case); diarrhea (1 case); and headache (1 case).
      Stable disease was observed in 41 patients for a median period of 23 months
      (range 2-35+). After first administration, average 4HPR peak plasma levels ranged
      from 0.6 to 6 micro M (after 100 and 4000 mg/m(2)/day, respectively) and
      increased 2-fold (to 1.3 and 12.9 micro M, respectively) after the 28-day
      treatment. 4HPR half-life increased from 17 h after the first administration to
      25 h after the 28(th) administration. Incidence of grade 2-3 toxicity was 0 of 12
      (0%), 7 of 22 (31%), and 4 of 8 (50%) with peak 4HPR concentrations <3 micro M, 3
      10 micro M, and >10 micro M, respectively. After repeated treatment, retinol
      levels decreased from 20 to 10% of pretreatment levels after all of the doses.
      CONCLUSIONS: In children, 4HPR administration up to 4000 mg/m(2)/day over 28
      days, followed by a 7-day interruption, results in manageable toxicity and in
      drug plasma concentrations comparable with those that induce apoptosis in
      neuroblastoma cell lines.

PMID- 12796366
TI  - Improvements in quality of life and disease-related symptoms in phase I trials of
      the selective oral epidermal growth factor receptor tyrosine kinase inhibitor
      ZD1839 in non-small cell lung cancer and other solid tumors.
AB  - PURPOSE: The feasibility and utility of assessing quality of life (QoL) and
      disease-related symptoms in patients with advanced cancer have been evaluated in
      two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal
      growth factor receptor tyrosine kinase inhibitor, in patients with advanced
      cancer. EXPERIMENTAL DESIGN: Functional Assessment of Cancer Therapy (FACT)
      questionnaires, including disease-specific subscales for lung, head and neck,
      colorectal, prostate, and ovarian cancer, were completed by patients in two open
      label, Phase I, escalating multiple-dose safety and tolerability trials. RESULTS:
      In 157 patients, 92% of whom had received prior therapy, compliance in returning
      FACT questionnaires was 87% (European/Australian trial) and 57% (United States
      trial). This did not appear to be influenced by dose level or tumor type. For
      patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial
      Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients
      with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and
      TOI scores did not deteriorate significantly, and in the United States trial,
      head and neck cancer scores improved significantly over time. In patients with
      NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L
      appeared sensitive to clinical change. CONCLUSIONS: QoL (FACT-L) questionnaires
      were used successfully in the Phase I clinical trials of ZD1839. They appeared to
      be a sensitive tool to monitor clinical changes for the five tumor types in these
      trials and showed that ZD1839 has the potential to improve patients' QoL.

PMID- 12796367
TI  - Phase I trial of ZD9331, a nonpolyglutamatable thymidylate synthase inhibitor,
      given as a 5-day continuous infusion to patients with refractory solid
      malignancies.
AB  - PURPOSE: This dose-escalating study investigated the toxicity, pharmacokinetics,
      and efficacy of the novel direct-acting antifolate ZD9331, given as a 5-day i.v.
      infusion every 3 weeks. EXPERIMENTAL DESIGN: Forty-five patients with refractory
      solid malignancies received ZD9331, which was escalated from 0.125 mg/m(2)/day.
      RESULTS: Dose-limiting grade 4 thrombocytopenia occurred in 3 of 6 patients
      treated at 8 mg/m(2)/day; other drug-related toxicities, across dose levels,
      included skin and gastrointestinal toxicity, lethargy, and asymptomatic,
      reversible, elevated transaminases. The maximum plasma concentration and area
      under the curve increased with dose. Clearance was dose-dependent and
      predominantly renal. At doses >/=2.4 mg/m(2)/day, plasma 2'-deoxyuridine levels
      were elevated consistently indicating inhibition of thymidylate synthase. Two
      patients had a partial response (breast, 1 patient; ovarian, 1 patient), and 10
      patients had stable disease. CONCLUSION: The maximum tolerated dose was defined
      as 6 mg/m(2)/day, and the toxicity profile for this regimen was considered
      acceptable and manageable. Administration of ZD9331 lead to elevation of 2'
      deoxyuridine levels, signifying thymidylate synthase inhibition, and evidence of
      antitumor activity was observed.

PMID- 12796368
TI  - A phase I study of recombinant human leukemia inhibitory factor in patients with
      advanced cancer.
AB  - PURPOSE: Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the
      interleukin 6 family of cytokines. We aimed to examine the safety,
      pharmacokinetics, and biological effects of recombinant human LIF (rhLIF,
      emfilermin) in patients with advanced cancer. EXPERIMENTAL DESIGN: In stage 1 of
      the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25
      16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2,
      40 patients received rhLIF or placebo, either once daily for 14 days commencing
      the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the
      day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was
      cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). RESULTS: In stage 1, platelet
      counts increased in most patients, including those who received placebo. Blood
      progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to
      baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0
      micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less
      severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2,
      increases in C reactive protein were seen at higher doses. Several patients
      developed evidence of autonomic dysfunction, in particular impotence and episodic
      hypotension. The dose-limiting toxicities were hypotension and rigors.
      Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of
      dose. CONCLUSIONS: We demonstrated a biological effect of rhLIF on blood
      progenitor cells, C reactive protein levels, and hemopoietic recovery after
      chemotherapy.

PMID- 12796369
TI  - Phase I and pharmacological study of oral 9-aminocamptothecin colloidal
      dispersion (NSC 603071) in patients with advanced solid tumors.
AB  - PURPOSE: 9-Aminocamptothecin colloidal dispersion (9-ACCD; NSC 603071) is a
      specific inhibitor of topoisomerase I that can be given p.o. This Phase I trial
      was conducted to determine the toxicity profile, maximal tolerated dose, and
      pharmacokinetics profile, including bioavailability, of p.o. 9-ACCD in patients
      with advanced solid tumors. EXPERIMENTAL DESIGN: After receiving one i.v. dose of
      9-ACCD, patients were treated with 9-ACCD p.o., starting with a 2-week schedule,
      to establish the safety. Once safety was established, patients were treated
      continuously for 4 weeks followed by a rest period of 2 weeks at dosages of 0.2,
      0.3, 0.45, 0.56, 0.7, and 0.63 mg/m(2)/day. Serial blood samples were collected
      for the pharmacokinetics study on day 1 after the i.v. dose and day 2 after p.o.
      administration. Lactone and total 9-aminocamptothecin were analyzed by high
      pressure liquid chromatographic assay. RESULTS: Thirty-two patients were treated
      on the study. The dose-limiting toxicity was myelosuppression at the dosage of
      0.7 mg/m(2)/day. Other toxic effects included nausea, vomiting, fatigue, and
      transient elevation of the total bilirubin level. The maximal tolerated dose was
      0.63 mg/m(2)/day. There was no objective response. The mean terminal half-life of
      p.o. total 9-ACCD was 1.2 +/- 1.2 h, and the volume of distribution was 17.7 +/-
      20.6 l/m(2). The mean bioavailability of total 9-ACCD was 68.1 +/- 36.4%.
      CONCLUSIONS: Despite good tolerance of p.o. administration, the lack of clinical
      activity and variable absorption of 9-ACCD suggested that further development
      might not be warranted.

PMID- 12796371
TI  - Effects of whole body hyperthermia (41.8 degrees C) on the frequency of tumor
      cells in the peripheral blood of patients with advanced malignancies.
AB  - PURPOSE: Combining heat with antineoplastic drugs has produced evidence of
      antitumor synergism. An increasing number of trials are investigating whole body
      hyperthermia (WBH) in combination with chemotherapy in patients with advanced
      malignancies. Here we investigated whether the hyperdynamic state of the
      circulation as a consequence of WBH may stimulate dissemination of malignant
      cells. EXPERIMENTAL DESIGN: WBH in combination with chemotherapy was administered
      by a radiant heat device to 20 consecutive patients with advanced epithelial
      malignancies. One WBH session lasted for approximately 4 h (90 min heating time,
      60 min plateau at 41.8 degrees C, and 60-80 min cooling). Peripheral blood was
      drawn before WBH treatment (baseline), at the end of the plateau (1 h), and 24 h
      and 48 h thereafter. After removal of leukocytes using anti-CD45 magnetic beads,
      circulating tumor cells were detected immunocytochemically using the monoclonal
      antibody A45-B/B3, which binds to a common epitope present on various
      cytokeratins. RESULTS: The method used to detect tumor cells in the peripheral
      blood proved to be specific and very sensitive (detection limit 1 tumor cell per
      1.7 x 10(5) peripheral blood mononuclear cell). Before WBH, 6 of 20 patients had
      cyto-keratin-positive cells in their blood. A treatment-induced increase in the
      number of circulating tumor cells became statistically significant at 24 h after
      WBH (P = 0.043) and was detected in a total of 9 patients, 5 of whom had no
      detectable malignant cells at baseline. There was no evidence of a correlation
      between an increase in the number of circulating tumor cells and increased
      metastasis frequency. CONCLUSIONS: Our findings suggest that WBH might induce a
      temporary release of tumor cells into the circulation, but this spread appears to
      be clinically not significant in patients with advanced malignancies.

PMID- 12796370
TI  - 10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with
      previously treated non-small cell lung cancer.
AB  - PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy
      in mouse xenograft models, likely attributable to increased uptake by the RFC-1
      folate transporter and greater intracellular polyglutamylation. In a previous
      Phase I trial, stomatitis was the dose-limiting (and only clinically significant)
      toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2
      weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in
      the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had
      stage IIIB or IV NSCLC and either no previous chemotherapy or progression after
      initial response or stable disease to one previous chemotherapy regimen.
      Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However,
      to decrease the frequency of stomatitis, the last 10 patients were treated at a
      dose of 135 mg/m(2). We planned to correlate PDX effects with folate and
      homocysteine levels and the expression of genes associated with folate transport
      and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom
      were evaluable for response. Four patients had confirmed, major objective
      responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4,
      9, 12, and 15 months. Twelve patients (31%) had stable disease. The median
      survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and
      36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had
      grade 3. No clinically significant myelosuppression occurred. No correlation
      between homocysteine or serum folate levels and severity of stomatitis was
      observed. Area under the curve (calculated using a limited sampling model)
      correlated with mucositis grade. A trend was noted between folate transporter
      expression and treatment effect. CONCLUSIONS: The broad applicability of this new
      antifolate with limited toxicity and proven efficacy in NSCLC encourage further
      development of this compound. Several trials are now underway combining PDX with
      other chemotherapeutic agents and testing its efficacy in other cancers.

PMID- 12796372
TI  - A phase I study of topotecan/paclitaxel alternating with etoposide/cisplatin and
      thoracic irradiation in patients with limited small cell lung cancer.
AB  - PURPOSE: Topotecan and paclitaxel are promising cytotoxic drugs with novel
      mechanisms of action relative to other chemotherapies used in the treatment of
      small cell lung cancer (SCLC). In an effort to integrate paclitaxel and topotecan
      into the treatment of limited disease (LD) SCLC, we conducted a Phase I study of
      these agents administered as initial induction therapy. EXPERIMENTAL DESIGN:
      Escalating doses of topotecan (0.8-1.4 mg/m(2) d1-5) and paclitaxel (110-175
      mg/m(2) d1) were administered i.v. every 21 days for two cycles to determine the
      maximum tolerated dose (MTD) in patients with LD SCLC. This was followed by two
      cycles of etoposide (120 mg/m(2) d1-3) and cisplatin (60 mg/m(2) d1) with
      thoracic radiotherapy. The first 5 subjects received 1.8 Gy once daily x 25
      fractions, while subsequent subjects received 1.5 Gy twice daily x 30 fractions.
      Two additional cycles of chemotherapy (topotecan and paclitaxel, followed by
      etoposide and cisplatin) were given. RESULTS: Common toxicities included grade
      >/=3 neutropenia in 67% of courses of topotecan and paclitaxel and grade >/=2
      esophagitis in 71% of patients. The MTD was based on toxicity during the first
      two cycles of chemotherapy and defined after accrual of 18 patients to four dose
      levels. Two of three patients developed grade 3 nonhematological toxicity
      (pneumonia) at the fourth dose level. Thus, the third dose level (topotecan 1.2
      mg/m(2), paclitaxel 160 mg/m(2)) was defined as the MTD recommended for Phase II
      studies. One subject died suddenly on day 2 of cycle 1 without autopsy
      confirmation of the etiology. A second subject died during cycle 3 due to
      thrombocytopenia, gastrointestinal bleeding, and respiratory failure. Response
      rates after induction of topotecan and paclitaxel: 16 of 18 (88.8%) partial
      response, 1 of 18 (5.5%) complete response. Response rates after completion of
      therapy: 10 of 18 (55.5%) partial response, 7 of 18 (38.8%) complete response.
      CONCLUSIONS: Induction topotecan and paclitaxel before chemoradiotherapy in
      patients with LD SCLC is feasible and results in expected toxicities. The outcome
      of a recently closed Cancer and Leukemia Group B Phase II study of similar design
      (CLB-39808) should help determine whether or not this approach warrants testing
      in a randomized setting.

PMID- 12796373
TI  - The effect of dose increase of imatinib mesylate in patients with chronic or
      accelerated phase chronic myelogenous leukemia with inadequate hematologic or
      cytogenetic response to initial treatment.
AB  - PURPOSE: Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for
      the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic
      myelogenous leukemia (CML). Some patients with chronic-phase or accelerated-phase
      CML either relapse after an initial response or are refractory to imatinib,
      prompting us to evaluate the efficacy of dose increase in such patients.
      EXPERIMENTAL DESIGN: Twelve chronic-phase patients initially receiving 400 mg/day
      and 4 patients with accelerated phase initially receiving either 400 mg/day (two
      patients) or 600 mg/day (two patients) had their dose increased (14 to 800 mg/day
      and 2 to 600 mg/day) because of progressive disease (usually clonal evolution) or
      inadequate cytogenetic response after at least 1 year of therapy. RESULTS: Six
      patients had major cytogenetic responses after dose increase (3 complete and 3
      partial). Two others had minor cytogenetic responses. Two patients with clonal
      evolution transiently lost the additional clonal aberrations. Almost all of the
      responses occurred within 6 months, and were typically 3-6 months in duration.
      However, 3 patients have continuing major cytogenetic responses of >18 months
      duration. Dose increase was well tolerated, with thrombocytopenia, mild
      leukopenia, and exacerbation of prior edema being the most common adverse events.
      CONCLUSIONS: Although increasing the dose of imatinib can benefit a subgroup of
      patients with CML with either an inadequate cytogenetic response or disease
      progression, our results suggest the majority will not have a sustained
      meaningful response, and that other options, such as allogeneic stem cell
      transplant or investigational therapies, also need to be considered at the time
      of dose increase.

PMID- 12796374
TI  - Dose escalation study of intravenous estramustine phosphate in combination with
      Paclitaxel and Carboplatin in patients with advanced prostate cancer.
AB  - PURPOSE: The purpose is to determine a safe weekly dose of i.v. estramustine
      phosphate (EMP) to combine with weekly paclitaxel and monthly carboplatin in
      patients with advanced prostate cancer. EXPERIMENTAL DESIGN: Patients with
      advanced prostate cancer (castrate and noncastrate) were administered escalating
      doses of weekly 1-h infusion of i.v. EMP (500-1000-1500 mg/m(2)) in combination
      with weekly paclitaxel (100 mg/m(2) over 1 h) and i.v. carboplatin (area under
      the curve 6 mg/ml-min every 4 weeks). Four weeks of therapy were considered one
      cycle. In the first three cohorts, EMP was given i.v. 3 h before paclitaxel.
      Cohorts 4 and 5 reversed the administration order: EMP (doses 1000-1500 mg/m(2))
      was given immediately after the end of paclitaxel infusion. Plasma levels of EMP
      and its metabolites, estramustine and estromustine, were monitored at time 0, at
      120 min, and approximately at 20, 21, and 168 h from the start of EMP infusion.
      Paclitaxel concentrations were determined at basal (0), 30, 60, 90, and 120 min
      and 18 h after the start of paclitaxel infusion, and a concentration-time curve
      was estimated. Pharmacokinetic evaluation was performed in cycles 1 and 2 during
      the first week of therapy. RESULTS: Nineteen patients were entered on the initial
      three dose levels (cohorts 1-3). Dose-limiting transient hepatic toxicity was
      encountered in cohort 3 (EMP = 1500 mg/m(2)). An additional 13 patients were
      treated with paclitaxel (100 mg/m(2)) first, followed by i.v. EMP at 1000 mg/m(2)
      (cohort 4), and 1500 mg/m(2) (cohort 5). No dose-limiting toxicities were seen,
      and cohort 5 was determined safe for Phase II studies. Thromboembolic events were
      observed in 9% of patients (no prophylactic coumadin was used). Plasma
      concentrations of EMP and metabolites increased proportionally with dose. In all
      cohorts, there was a slight decrease in EMP and estramustine plasma
      concentrations between cycles 1 and 2. Although not significant, higher levels of
      estromustine at cycle 2 were observed in comparison to cycle 1. Decreased
      clearance of paclitaxel leading to higher than expected paclitaxel plasma
      concentrations was observed during the first cycle of therapy. Paclitaxel plasma
      concentrations were lower during cycle 2. In 17 patients with androgen
      independent disease, 59% had >/=50% posttherapy decline in PSA and 22% showed
      measurable disease regression. CONCLUSIONS: The regimen of weekly i.v. EMP in
      combination with paclitaxel and carboplatin can be safely administered with
      hepatic toxicity being transient and reversible. Pharmacokinetic results suggest
      that EMP competitively inhibits the biotransformation of paclitaxel after the
      first administration. This effect is counterbalanced, after repeated
      administrations, by a possible induction of the metabolic system caused by EMP.
      Phase II testing is ongoing to evaluate the efficacy of this combination.

PMID- 12796375
TI  - Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine
      phosphorylase gene in the majority of pleural mesotheliomas.
AB  - PURPOSE: Homozygous deletions at chromosome region 9p21 targeting the CDKN2A gene
      have been reported as a common cytogenetic abnormality in mesothelioma. MTAP, a
      gene approximately 100-kb telomeric to CDKN2A, encodes methylthioadenosine
      phosphorylase, an enzyme essential in the salvage of cellular adenine and
      methionine, and its codeletion with CDKN2A has been reported in other tumors. The
      aim of this study was to define the prevalence of homozygous deletion of CDKN2A
      alone or in combination with MTAP in a large series of pleural mesothelioma.
      EXPERIMENTAL DESIGN: We used a fluorescent in situ hybridization assay for CDKN2A
      and MTAP on interphase nuclei in imprints of frozen tissue from 95 cases of
      pleural mesothelioma. Histologically, the cases were classified as epithelial
      (71), biphasic (19) and sarcomatous (5). In each experiment, a 9p21 locus
      specific probe and a chromosome 9 centromeric probe were used and fluorescent in
      situ hybridization signals for both probes were simultaneously recorded in at
      least 100 nuclei. Cases were considered homozygously deleted if both 9p21 signals
      were lost in at least 20% of nuclei. RESULTS: Overall, 70 cases (74%) had
      homozygous deletion of CDKN2A. MTAP was codeleted in 64 of these cases (91%). No
      case with MTAP deletion without CDKN2A deletion was identified. Homozygous loss
      of CDKN2A was seen in 49 of 71 epithelial (70%), 16 of 19 biphasic (89%), and 5
      of 5 sarcomatous (100%) mesotheliomas. CONCLUSIONS: Homozygous deletion of CDKN2A
      is seen in the majority of pleural mesotheliomas, and MTAP is codeleted in most
      of these cases. Previous cell line studies have shown that loss of MTAP renders
      cells dependent on de novo synthesis of purine derivatives. Thus, the
      particularly high prevalence of MTAP codeletion in mesothelioma makes it an ideal
      candidate for trials of targeted therapy using inhibitors of de novo AMP
      synthesis (e.g., L-alanosine).

PMID- 12796376
TI  - Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed
      Sternberg cells of classical Hodgkin's lymphoma: associations with presenting
      features, serum interleukin 10 levels, and clinical outcome.
AB  - PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and
      Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its
      clinical significance is controversial. We correlated LMP-1 with presenting
      features, including serum interleukin 10 levels and clinical outcome.
      EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were
      untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression
      was determined by immunohistochemistry. RESULTS: We identified 577 patients with
      cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in
      HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with
      nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001
      by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had
      higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303
      patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or
      equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1
      positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P
      = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP
      1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P =
      0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS
      and OS in patients treated with other regimens or with radiotherapy alone.
      CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with
      mixed cellularity type and higher serum interleukin 10 levels. The presence of
      LMP-1 was not associated with FFS or OS in uniformly treated patients.

PMID- 12796377
TI  - The human T-cell factor-4 gene splicing isoforms, Wnt signal pathway, and
      apoptosis in renal cell carcinoma.
AB  - beta-Catenin and transcriptional factor TCF-4 (human T-cell factor-4) genes
      comprise the Wnt signal. The Wnt signal pathway plays an important role in
      malignant transformation. We hypothesize that the beta-catenin and TCF-4 gene and
      Wnt signal are important in the progression of renal cell carcinoma (RCC). To
      test this hypothesis, we investigated TCF-4 splicing isoforms, beta-catenin, and
      Wnt signal pathway (cyclin D1, c-myc, c-jun, and MMP7) in three RCC cell lines
      (A498, Caki-1, and Caki-2), 38 primary RCCs, and 29 normal kidney samples. We
      also analyzed the relationship between TCF-4 gene splicing isoforms,
      proliferation (proliferating cell nuclear antigen labeling index), and apoptosis
      [antiapoptotic factors (Bcl-2 and Bcl-x(L)), proapoptotic factors (Bak and Bax),
      and caspase-3] in RCC samples. In 38 RCC samples, four splicing isoforms of the
      TCF-4 gene were present in the region between exon 12 and exon 17. Thirty (79%)
      of 38 RCCs and all (100%) of the normal kidney samples showed mixed isoforms with
      both long and short reading frames in the COOH-terminal region, whereas the
      remaining 8 RCC samples showed only the long-form reading frame. Two COOH
      terminal-binding protein sites were present only in the long-form reading frame.
      The eight RCCs that demonstrated only the long reading frame isoform showed early
      disease progression and poor prognosis. In these 8 RCC samples, down-regulation
      of cyclin D1, c-myc, c-jun, and MMP7 expression was observed at the mRNA level.
      In addition, a marked reduction of caspase-3 expression was also found at both
      the mRNA and the protein level. However, the beta-catenin gene was not
      overexpressed at the mRNA level and protein level, and mutation and deletion were
      not observed in exon 3. In these three renal cell lines, there was no significant
      difference in TCF-4 mRNA expression before and after 5-Aza-2'-deoxycytidine
      treatment, and there appeared to be no splicing isoforms in the region between
      exon 1 and exon 11. These findings suggest that alteration in beta-catenin is an
      infrequent event in RCC. In samples in which beta-catenin was not overexpressed,
      the target genes of Wnt signal were regulated through TCF-4 splicing isoforms.
      The imbalance between TCF-4 gene splicing isoforms with long and short reading
      frames is associated with RCC progression through the inhibition of the apoptotic
      pathway. We demonstrate for the first time that TCF-4 gene splicing isoforms and
      the Wnt signal pathway can induce progression of RCC by the inhibition of
      apoptosis and not by the induction of cell proliferation.

PMID- 12796378
TI  - The t(14;18) is associated with germinal center-derived diffuse large B-cell
      lymphoma and is a strong predictor of outcome.
AB  - The t(14;18) is present in a significant proportion of diffuse large B-cell
      lymphomas (DLBCLs), however, the prognostic effect of the translocation and the
      relationship with transformed follicular lymphoma remains controversial. To
      clarify these uncertainties, interphase fluorescence in situ hybridization (FISH)
      was used to determine the incidence of the t(14;18) in nodal DLBCL, and this was
      correlated with BCL2 expression, germinal center (GC) immunophenotype, and
      patient outcome. FISH was performed on paraffin-extracted nuclei from 137 de novo
      nodal DLBCLs. Eighteen of 137 de novo DLBCLs were t(14;18) positive. The t(14;18)
      was most commonly associated with the subset of DLBCLs that expressed a GC
      phenotype, defined as CD10+, BCL6+ (GC-type DLBCL): positive in 14 of 47 (30%)
      cases, compared with 4 of 89 (5%) in the non-GC group (Pearson's chi(2) = 28.4; P
      < 0.0001). All cases with a translocation expressed BCL2 protein, however, 40
      expressed BCL2 protein without a t(14;18). GC-type DLBCL patients with a t(14;18)
      had a significantly worse survival compared with GC-type DLBCL patients without
      the translocation (2-year survivals were 29 and 63%, respectively; P = 0.006). Of
      the cases without the translocation, BCL2 protein expression did not affect
      survival. In contrast, in the non-GC group of DLBCLs, BCL2 protein expression
      reduced the 2-year overall survival from 64% in the BCL2-negative group to 38%,
      with a median survival of 15.0 months (P = 0.02). In conclusion, the t(14;18) is
      common in DLBCLs, particularly in GC-type DLBCLs, where the presence of the
      translocation has a poor prognostic effect. BCL2 protein expression defines a
      group of non-GC DLBCL patients with a poor prognosis.

PMID- 12796379
TI  - Overexpression and constitutive activation of FLT3 induces STAT5 activation in
      primary acute myeloid leukemia blast cells.
AB  - PURPOSE: Activating length mutations in the juxtamembrane domain (FLT3-LM) and
      mutations in the tyrosine kinase domain (FLT3-TKD) of FLT3 represent the most
      frequent genetic alterations in acute myeloid leukemia (AML). However, the
      functional role of active FLT3 mutants in primary AML blast cells is not well
      characterized. EXPERIMENTAL DESIGN: We analyzed the transforming potential and
      the signaling of FLT3-ITD mutants in Ba/F3 cells and in primary AML blasts.
      RESULTS: FLT3-ITD mutants induce an autophosphorylation of the receptor,
      interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen
      activated protein kinase (MAPK) activation. In contrast to the FLT3-ITD mutants,
      the ligand-stimulated FLT3-WT receptor was unable to transduce a fully
      proliferative response in Ba/F3 and monocytic OCI-AML5 cells. The ligand
      stimulated FLT3-WT receptor activated AKT and MAPK, but not STAT5. In primary
      blast cells from 60 patients with AML, FLT3 was expressed in 91.9% of patients
      carrying a FLT3-LM/TKD mutation compared with 77.8% in FLT3-LM/TKD-negative
      patients. STAT3 and STAT5 were constitutively activated in 76 and 63% of
      patients, respectively. In accordance with the results in Ba/F3 cells, a high
      FLT3 expression and the presence of a FLT3-LM was strongly associated with the
      STAT5 but not with the STAT3 activation in primary AML blast cells. Moreover, the
      constitutive tyrosine phosphorylation of STAT5 was efficiently down-regulated by
      a FLT3 protein tyrosine kinase inhibitor in AML cells expressing an active FLT3
      mutant. CONCLUSIONS: Active FLT3 receptor mutants have transforming potential in
      hematopoietic cells and induce a strong activation of STAT5 in primary AML cells.
      The FLT3-STAT5 pathway contributes to the malignant phenotype and represents a
      promising molecular therapeutic target structure in AML.

PMID- 12796380
TI  - Age-associated increase of codon 72 Arginine p53 frequency in gastric cardia and
      non-cardia adenocarcinoma.
AB  - PURPOSE: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has
      been associated with human cancer susceptibility and prognosis. To examine the
      role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients
      with or without the cancer. EXPERIMENTAL DESIGN: DNA samples were extracted from
      archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma
      and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP.
      RESULTS: The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were
      7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of
      codon 72 Arg p53 with age was observed in patients with gastric cancer, but not
      in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a
      significantly higher frequency of homozygous Arg allele than those with non
      cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and
      gender, a logistic regression analysis suggested that the risk for a p53 Arg
      homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4
      7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous
      patients. No close relationship was observed among patient gender, tumor
      histological type, p53 protein expression, and codon 72 genotype distribution.
      CONCLUSIONS: These findings indicate that codon 72 Arg p53 may be associated with
      a prolonged survival for patients who have had gastric adenocarcinoma, especially
      non-cardia adenocarcinoma. It may confer, however, a different role on patients
      who suffer cardia gastric adenocarcinoma.

PMID- 12796381
TI  - Focal adhesion kinase is expressed in the angiogenic blood vessels of malignant
      astrocytic tumors in vivo and promotes capillary tube formation of brain
      microvascular endothelial cells.
AB  - PURPOSE: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that has
      been shown to promote proliferation, migration, and invasion of several cell
      types in vitro, and we have shown recently that FAK promotes proliferation of
      malignant astrocytoma cells in vivo. To determine the role of FAK in angiogenesis
      in malignant astrocytic tumors, we investigated the expression and function of
      FAK in brain endothelial cells. EXPERIMENTAL DESIGN: We characterized the
      expression of FAK and activated FAK in endothelial cells by immunohistochemistry.
      We also determined the function of FAK in brain microvascular endothelial cells
      by transfecting these cells with a dominant interfering form of FAK [FAK-related
      nonkinase (FRNK)] or a mutant FRNK (Leu-1034 to Ser) and assessed the effect on
      capillary tube formation and cell migration. RESULTS: We found that FAK was
      expressed in the endothelial cells of grade III (4 of 9 samples) and IV (9 of 10
      samples) astrocytoma biopsies but not in the endothelial cells of normal brain (0
      of 9 samples) and not in grade I (0 of 5 samples) or II (0 of 4 samples)
      astrocytoma biopsies. Furthermore, we found that both FAK and activated FAK were
      expressed in the endothelial cells in malignant astrocytoma tumors propagated
      intracerebrally in the severe combined immunodeficient mouse brain. As expected,
      immunofluorescence analysis showed FRNK protein to localize to focal adhesions,
      whereas mutant FRNK protein did not. FRNK-transfected endothelial cells showed a
      55% reduction in branched tube formation and a 40% reduction in tube length when
      propagated in three-dimensional collagen gels, compared with cells transfected
      with the mutant FRNK construct. Furthermore, FRNK-transfected cells showed a 35
      50% reduction in haptotactic migration toward fibronectin and collagen, compared
      with mutant FRNK-transfected cells. CONCLUSIONS: These data suggest that FAK
      promotes angiogenesis and that this occurs, at least in part, through the
      promotion of endothelial cell migration.

PMID- 12796382
TI  - In vivo activation of signal transducer and activator of transcription 1 after
      CD154 gene therapy for chronic lymphocytic leukemia is associated with clinical
      and immunologic response.
AB  - PURPOSE: Signal transducer and activator of transcription (STAT) proteins are
      important regulators of physiological stimuli in lymphocytes. Biological
      therapies directed at lymphocytic malignancies such as chronic lymphocytic
      leukemia (CLL) may be mediated by these transcription factors. One such approach,
      CD154 (CD40-ligand) gene therapy, involves expressing CD154 on malignant B cells
      from CLL patients by transduction with an adenovirus vector after which the cells
      are reinfused into the patients. To determine the intracellular signaling
      pathways that underlie the clinical and immunological responses observed in
      patients from a Phase I study of CD154 gene therapy, CLL cells from these
      patients were examined for changes in STAT signaling events. EXPERIMENTAL DESIGN:
      CLL cells from patients who underwent CD154 gene therapy were analyzed for
      changes in STAT signaling by Western blot analysis and electrophoretic mobility
      shift assay. Activation of STAT1 was correlated with patient response to therapy.
      RESULTS: Tyrosine phosphorylation of STAT1 was detected in the nontransduced CLL
      cells in 9 of 11 patients 24 h after infusion, but not before. Activation of
      STAT1 was associated with clinical response, as measured by decreased absolute
      lymphocyte count, and immunological response, as measured by elevated plasma
      levels of IFN-gamma. CONCLUSION: This study indicates that STAT signaling may be
      an important mediator of biological treatments, such as CD154 gene therapy, and
      that early STAT1 activation may predict response to this novel treatment.

PMID- 12796383
TI  - -174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum
      level in patients with colorectal cancer.
AB  - PURPOSE: Experimental data suggest that interleukin 6 (IL-6) plays an important
      role in the development and progression of metastasis from colorectal cancer
      (CRC), and -174 G>C polymorphism has been identified recently in the IL-6 gene
      promoter. Therefore, the aim of the present study was to investigate the
      significance of this type of polymorphism in patients with CRC. EXPERIMENTAL
      DESIGN: Using enzyme immunoassay, IL-6 concentrations were measured in
      preoperative serum samples from 65 stage I-IV CRC patients. DNA was extracted
      from peripheral blood mononuclear cells, and -174 G>C polymorphism detected using
      PCR, followed by NlaIII restriction enzyme digestion and electrophoresis.
      RESULTS: The median IL-6 serum level was 0.14 pg/ml in patients with stage I-III
      disease versus 0.41 pg/ml in patients with stage IV disease (P < 0.001). DNA
      amplification was possible in 62 cases. On grouping genotypes at the -174 G>C
      locus as C+ (CC and CG) and C- (GG), a significant association was observed
      between the type of polymorphism and IL-6 serum level: the median value for IL-6
      was 0.14 pg/ml in C+ patients (n = 32) and 0.32 pg/ml in C- patients (n = 30; P =
      0.034). Moreover, in patients with hepatic metastasis the median level of IL-6
      was 0.23 pg/ml in C+ patients (n = 9) and 0.96 pg/ml in C- patients (n = 9; P =
      0.004). CONCLUSIONS: In patients with CRC, the -174 G>C polymorphism status of
      the IL-6 gene promoter affects the IL-6 serum level, particularly in the presence
      of hepatic metastasis.

PMID- 12796384
TI  - Loss of p16 expression has prognostic significance in human nasopharyngeal
      carcinoma.
AB  - PURPOSE: p16 is an important inhibitor of cell cycle progression; absence of p16
      can thus result in increased cellular proliferation. In nasopharyngeal carcinoma
      (NPC), absence of p16 has been reported in association with presence of the EBV
      and pRb. We therefore examined p16, pRb, and EBV-encoded RNA (EBER) expression in
      biopsy specimens from 84 patients with newly diagnosed NPC, who were treated
      primarily with curative radiation therapy. Our objective was to determine whether
      there was a correlation between these parameters and clinical outcome in NPC.
      EXPERIMENTAL DESIGN: Sections were cut from archival formalin-fixed, paraffin
      embedded tumor blocks from NPC patients. p16 and pRb expression were determined
      using polyclonal and monoclonal antibodies, respectively. The presence of EBV was
      determined by in situ hybridization for EBER. The percentage of positively
      staining tumor nuclei was scored for p16 or pRb immunoreactivity. Relative
      intensity and proportion of cells with EBER signals were also documented.
      RESULTS: p16 expression was reduced (</=5% positive immunoexpression) in 59 of 84
      (70%) NPC samples; in contrast, pRb was observed in all (100%) tumors. EBER
      signals were detected in 67 of 83 (81%) NPC specimens. There was a weak
      correlation between EBER presence and loss of p16 (P = 0.1). Using a Cox
      regression model controlling for known prognostic parameters, such as age, weight
      loss, and tumor stage, complete absence of p16 expression (0%, i.e., no
      immunostaining identified throughout the specimen) was associated with an
      inferior overall survival rate (P = 0.022). In addition, EBER-positive NPC was
      strongly associated with improved overall survival (P = 0.005) as reported
      previously (Shi et al., Cancer, 94: 1997, 2002). CONCLUSION: These results
      provide the first evidence suggesting that inactivation of p16 appears to be a
      significant predictor for poor overall survival in NPC. Given that reduced p16
      expression is observed in the majority of patients with NPC, this indicates that
      therapeutic strategies targeting the p16 pathway may be a biologically rational
      approach for NPC. The favorable prognostic value of EBER suggests that future
      clinical trials with NPC should consider stratifying for EBER status.

PMID- 12796385
TI  - The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in
      prostate biopsy specimens distinguishes organ-confined from advanced prostate
      cancer at radical prostatectomy.
AB  - PURPOSE: To determine whether the expression ratio of matrix metalloproteinase
      (MMP) to E-cadherin mRNA (MMP:E-cadherin) in biopsy (BX) samples of prostate
      cancer correlate with that of radical prostatectomy (RP) specimens and assists in
      predicting pathologic stage. EXPERIMENTAL DESIGN: The mRNA expression levels for
      MMP-2 and -9 and of E-cadherin were determined by a colorimetric in situ
      hybridization assay in 44 paired BX and RP specimens. Clinical stage, BX Gleason
      score (GS), total length of cancer in BX cores, and serum prostate-specific
      antigen levels were also assessed. RESULTS: Clinical stage was confined in 39 of
      44 (89%) patients. Subsequent to RP, however, only 17 of 44 (39%) patients had
      proven organ-confined disease (pT2). BX GSs agreed with the RP GS in 77% of RP
      specimens. We found a strong correlation between BX and RP MMP:E-cadherin ratios
      (correlation coefficient = 0.755). The ratio increased as the GS increased and
      pathologic stage advanced (pT2 versus >/= pT3). Increasing clinical stage, GS,
      and serum prostate-specific antigen were significantly associated with advanced
      cancer at RP (P = 0.004-0.0001). The BX MMP:E-cadherin ratio, however, exhibited
      the strongest association with pathologic stage and independently predicted the
      status of 89% of the RP cases based on a BX ratio of <6 (predicted stage pT2
      cancer at RP) versus >/=6 (predicted stage >/= pT3 at RP). CONCLUSION: The BX
      MMP:E-cadherin ratio represents a novel prognostic assay for predicting stage of
      cancer at RP. These data provide proof of principle for directly assessing the
      biological potential of prostate cancer using molecular strategies in patient's
      specimens.

PMID- 12796386
TI  - Value of immunohistochemical markers in preinvasive bronchial lesions in risk
      assessment of lung cancer.
AB  - PURPOSE: Bronchial carcinogenesis is a multistep process characterized by
      accumulation of genetic and molecular abnormalities, which precedes and
      accompanies the preinvasive lesions known as dysplasia and carcinoma in situ
      (CIS). We hypothesized that the level of accumulated molecular abnormalities in
      dysplasia assessed by immunohistochemical markers might reflect the severity of
      the carcinogenic process, thus allowing for risk assessment in smokers.
      EXPERIMENTAL DESIGN: We performed a prospective analysis of bronchial biopsies in
      48 former smokers who had at least one area of metaplasia. Twenty-two of the
      patients had a previous history of lung cancer. Eighty bronchial lesions were
      recorded at baseline, including 31 metaplasia, 12 mild dysplasia, 9 moderate
      dysplasia, 9 severe dysplasia, and 19 CISs. Forty-one percent of the patients had
      multiple preinvasive lesions. Immunohistochemical analysis of P53, cyclin D1,
      cyclin E, Bax, and Bcl2 was performed. Aberrant expression of one of these
      proteins as compared with normal bronchi was recorded as one molecular
      alteration. RESULTS: After 18 months, 17 patients were diagnosed with lung
      cancer. No isolated parameter, including dysplastic grade or any isolated
      molecular alteration, was significantly associated with cancer occurrence at 18
      months follow-up, using a logistic regression statistical analysis. In contrast,
      considering CIS and cancer as end point, more than two immunohistochemical
      abnormalities were associated with cancer or CIS occurrence (P = 0.02).
      CONCLUSIONS: We concluded that the cumulative index of immunohistochemical
      abnormalities in a random dysplasia is associated with CIS or lung cancer in the
      cancerization field of symptomatic smokers, independently of the
      histopathological grade of dysplasia. This set of histopathological biomarkers
      might be useful in risk assessment and provide intermediate end points for
      chemopreventive trials.

PMID- 12796387
TI  - Expression of fatty acid synthase as a prognostic indicator in soft tissue
      sarcomas.
AB  - PURPOSE: Fatty acid synthase (FAS) is a key enzyme in the de novo biosynthesis of
      fatty acids. Carcinoma cells are dependent on endogenous fatty acid synthesis for
      growth in vitro. In a subset of human cancers, elevated FAS is associated with
      poor prognosis; however, the expression of FAS and the relationship between FAS
      and prognosis in soft tissue sarcomas (STSs) have not been studied. The objective
      of this study is to examine the expression of FAS in STSs and determine its
      relationship to clinicopathological features and prognosis. EXPERIMENTAL DESIGN:
      Sixty-four cases of STS were examined. The clinicopathological features and
      immunohistochemical expression of FAS and Ki-67 antigen were studied. Survival
      analysis was performed using the log-rank test and the Cox multivariate
      regression model. RESULTS: FAS expression was observed in 20 of 64 cases (31.3%)
      of STS. FAS-positive sarcomas were found in 13 of 23 malignant fibrous
      histiocytomas, 3 of 17 liposarcomas, 3 of 7 malignant peripheral nerve sheath
      tumors, and 1 extraskeletal mesenchymal chondrosarcoma. No expression of FAS was
      seen in the synovial sarcomas, leiomyosarcomas, or rhabdomyosarcomas that were
      examined. Clinicopathologically, FAS-positive tumors were significantly deep
      seated (P = 0.02) and large in size (P = 0.03). FAS expression correlated with
      decreased disease-free survival (P = 0.006) and decreased overall survival (P =
      0.003). In a multivariate analysis, expression of FAS was able to predict
      decreased disease-free survival but did not reach the level of significance for
      overall survival. CONCLUSIONS: FAS expression is one of the predictive indicators
      for disease prognosis in STS.

PMID- 12796388
TI  - Prognostic significance of MUC-1 expression in systemic anaplastic large cell
      lymphoma.
AB  - Systemic anaplastic large cell lymphoma (ALCL) frequently carries the
      t(2;5)(p23;q35) and overexpresses anaplastic lymphoma kinase (ALK). MUC-1, a
      highly glycosylated transmembrane protein, is detected in normal and malignant
      epithelial cells and has been associated with a poorer patient survival in
      various human malignancies. We have shown previously that MUC-1 is expressed as a
      consequence of t(1;14)(q21;32) in a subset of diffuse large B-cell lymphomas.
      ALCLs are known to express MUC-1, but its clinical significance is undefined. For
      this study, eligible patients with ALCL were HIV negative, received anthracycline
      containing regimens, and had pretreatment archival tissue. Expression of MUC-1
      and ALK was determined immunohistochemically after heat-induced antigen
      retrieval. A 10% cutoff for MUC-1 positivity was used. We identified 63 patients
      with systemic ALCL (22 ALK+, 41 ALK-) with a median age of 47 years, and 41 were
      male. MUC-1 was detected in 16 of 22 (73%) ALK-positive and 20 of 41 (49%) ALK
      negative ALCL (P = 0.06, chi(2) test). MUC-1 expression was not associated with
      apoptotic rate as detected by terminal deoxynucleotidyl transferase-mediated nick
      end labeling assay or proliferation index as evaluated by MIB-1 antibody. For 48
      patients with ALCL (16 ALK+, 32 ALK-) and complete clinical follow-up, 5-year
      progression-free survival (PFS) was 39.7% for patients with MUC-1-positive tumors
      versus 75.2% (P = 0.027 by Log-rank) for patients with MUC-1-negative tumors. For
      the ALK-negative ALCL group of 32 patients, the 5-year PFS was 26 versus 70.8%
      for patients with MUC-1-positive versus MUC-1-negative tumors (P = 0.0096 by Log
      rank). For the ALK-positive ALCL group of 16 patients, the 5-year PFS was 52
      versus 100% for patients with MUC-1-positive versus MUC-1-negative tumors (P, not
      significant). In summary, MUC-1 is frequently expressed in systemic ALCL, and its
      expression is associated with significantly inferior outcome in patients
      untreated previously with ALK-negative tumors. Future studies should explore the
      underlying molecular mechanisms of MUC-1 expression in these tumors and its role
      as a target for novel therapeutic strategies.

PMID- 12796389
TI  - PC cell-derived growth factor (granulin precursor) expression and action in human
      multiple myeloma.
AB  - PURPOSE: Multiple myeloma (MM) is a clonal B-cell neoplasm. PC cell-derived
      growth factor (PCDGF) is a M(r) 88,000 glycoprotein growth factor. Our objective
      was to investigate the expression, function, and signaling pathways of PCDGF in
      human MM. EXPERIMENTAL DESIGN: PCDGF expression, function, and signaling pathways
      in human MM were studies using two human MM cell lines: ARP-1 and RPMI 8226. In
      addition, PCDGF expression in MM patients was examined using 13 human bone marrow
      biopsy samples. RESULTS: PCDGF mRNA and protein expression was detected in human
      MM cell lines such as ARP-1 and RPMI 8226. PCDGF added exogenously stimulated
      cell growth and sustained cell survival of both ARP-1 and RPMI 8226 cells in a
      dose- and time-dependent fashion. Conversely, treatment with neutralizing anti
      PCDGF antibody inhibited the growth of RPMI 8226 cells suggesting that PCDGF acts
      as an autocrine growth factor for MM cells. Studies of signal transduction
      pathways showed PCDGF stimulated mitogen-activated protein kinase and
      phosphatidylinositol 3'-kinase pathways but not the Janus-activated kinase-signal
      transducer and activator of transcription pathway. Immunohistochemical analysis
      of bone marrow smears obtained from MM patients indicated that PCDGF expression
      was associated with myeloma cells from MM patients and correlated with the
      presence of MM disease. CONCLUSION: These data suggest that PCDGF is an autocrine
      growth factor in the cell growth and survival of human MM cells, and may be a
      potential candidate as a biomarker of MM cells.

PMID- 12796390
TI  - Association of serum estrone levels with estrogen receptor-positive breast cancer
      risk in postmenopausal Japanese women.
AB  - PURPOSE: Several reports have demonstrated the association between high serum
      estrogens levels and breast cancer risk in postmenopausal women. It is
      hypothesized that breast cancers arising in postmenopausal women with high serum
      estrogens levels are more likely to be estrogen receptor (ER)-positive. Thus, we
      have investigated whether or not high serum estrone (E(1)) levels are associated
      with ER-positive breast cancer risk in postmenopausal women. EXPERIMENTAL DESIGN:
      A case-control study was conducted on 71 cases (postmenopausal breast cancer
      patients) and 73 controls (postmenopausal healthy women). Serum E(1) levels were
      examined in their association with breast cancer risk after adjustment for the
      various epidemiological risk factors. In addition, clinicopathological
      characteristics of breast cancers arising in the women with high E(1) levels were
      investigated. RESULTS: Women in the high tertile of E(1) levels had a
      significantly (P < 0.01) increased risk of breast cancer as compared with women
      in the low tertile [odds ratio (OR), 4.14; 95% confidence interval (CI), 1.44
      11.87]. Subset analysis according to the ER status showed that women in the high
      tertile of E(1) levels had a significantly increased risk for ER-positive breast
      cancer (OR, 23.79; 95% CI, 3.50-161.59) but not for ER-negative breast cancer
      (OR, 1.45; 95% CI, 0.41-5.15) as compared with women in the low tertile. Tumor
      size and lymph node status were not significantly different between women in the
      high tertile and those in the intermediate and low tertiles. But the frequency of
      low-histological-grade tumors and ER-positive tumors (88 and 67%, respectively)
      showed a greater trend toward an increase (P = 0.06 and P = 0.07, respectively)
      in women in the high tertile than those (69 and 46%, respectively) in the
      intermediate and low tertiles. In addition, ER levels in ER-positive tumors were
      significantly (P < 0.05) higher in women in the high tertile (245.3 +/- 37.1
      fmol/mg protein) than those in the intermediate and low tertiles (134.0 +/- 31.3
      fmol/mg protein). CONCLUSIONS: Postmenopausal women with high serum E(1) levels
      have a significantly increased risk for ER-positive, but not ER-negative, breast
      cancer. Breast cancers arising in women with high E(1) levels show a high ER
      positivity as well as high ER content. Measurement of serum E(1) levels would be
      clinically useful in the selection of postmenopausal women who can benefit from
      prophylactic use of tamoxifen because tamoxifen can prevent ER-positive, but not
      ER-negative, breast cancer.

PMID- 12796391
TI  - Overexpression of hypoxia-inducible factor 1alpha indicates diminished response
      to radiotherapy and unfavorable prognosis in patients receiving radical
      radiotherapy for cervical cancer.
AB  - PURPOSE: The purpose is to investigate the impact of hypoxia-inducible factor
      (HIF)-1alpha expression on response to radiotherapy and prognosis of patients
      with primary irradiated cervical cancer. Because human papillomavirus (HPV)
      oncoprotein E6 might interact with HIF-1alpha in various pathways, we also
      investigated the relation of HIF-1alpha and HPV status. EXPERIMENTAL DESIGN:
      Expression of HIF-1alpha was investigated by immunohistochemistry in 67 specimens
      of patients who had received radical radiotherapy for cervical cancer stages IB
      IIIB. HPV analysis was performed using type-specific PCR, cloning, and
      sequencing. Survival analysis was performed using univariate and multivariate
      analysis. RESULTS: Immunohistochemistry revealed expression of HIF-1alpha in
      72.1% of the tumor samples. In 16 (23.9%) cases, there was a weak expression, in
      25 (37.3%) a moderate expression, and in 7 cases (10.4%) a strong expression of
      HIF-1alpha. Nineteen samples (28.4%) were considered negative for HIF-1alpha
      expression. Strong/moderate expression of HIF-1alpha was associated with only
      partial response to radiotherapy (P = 0.037, chi(2) test). Strong/moderate
      expression of HIF-1alpha was also an independent prognostic factor for shorter
      progression-free survival (P = 0.036, Cox regression) and cervical cancer
      specific survival (P = 0.04, Cox regression). No association between HIF-1alpha
      expression and infection with different HPV types could be found. CONCLUSIONS:
      Overexpression of HIF-1alpha has predictive and prognostic significance in
      cervical cancer patients receiving curative radiation therapy. Possibly,
      expression of HIF-1alpha could serve as intrinsic marker of hypoxia in cervical
      cancer.

PMID- 12796392
TI  - Expression and prognostic significance of kit, protein kinase B, and mitogen
      activated protein kinase in patients with small cell lung cancer.
AB  - PURPOSE: The Kit receptor has been proposed as a key molecular target for the
      treatment of small cell lung cancer (SCLC). Protein kinase B (PKB/Akt) and
      mitogen-activated protein kinase (MAPK) are intracellular kinases that regulate
      cell survival and proliferation and may play a role in Kit signal transduction.
      This study was designed to examine the expression and importance of Kit, PKB/Akt,
      and MAPK relative to standard clinical prognostic factors in SCLC. EXPERIMENTAL
      DESIGN: Kit, PKB/Akt, and MAPK expression was assessed by immunohistochemistry in
      SCLC biopsies. Clinical data were collected on tumor stage, weight loss,
      hematology, biochemistry, response to treatment, and survival. Univariate and
      multivariate analyses were performed to evaluate prognostic significance.
      RESULTS: Biopsies from 42 patients were evaluable, and significant Kit expression
      (>/=35% cells) was detected in 51% of the tumors, phosphorylated PKB/Akt was
      detected in 62% of the tumors, and phosphorylated MAPK was detected in 48% of the
      tumors. Neither Kit nor PKB/Akt expression predicted for survival. Only increased
      expression of cytoplasmic MAPK was prognostic for survival (median, 1 year for
      negative staining versus 1.8 years for positive staining; P = 0.0054).
      CONCLUSIONS: Kit, PKB/Akt, and MAPK are expressed in a high percentage of SCLCs,
      and our data suggest that MAPK is an independent positive predictive factor in
      this malignancy.

PMID- 12796393
TI  - Expression and activation of the nerve growth factor receptor TrkA in serous
      ovarian carcinoma.
AB  - PURPOSE: The purpose is to analyze the possible correlation between expression
      and activation of the high-affinity nerve growth factor (NGF) receptor TrkA, cell
      cycle protein expression, and disease outcome in serous ovarian carcinoma. In
      addition, we wished to study the possible link between expression of NGF, a novel
      angiogenic factor and its receptor TrkA, and the expression of factors involved
      in angiogenesis in effusions and solid tumors. EXPERIMENTAL DESIGN: Sections from
      80 malignant effusions and 65 corresponding solid tumors were evaluated for
      protein expression of NGF, TrkA, and phospho-TrkA (p-TrkA). Effusions were
      additionally studied for expression of p53, p21(WAF1/CIP1), Ki-67, and the M(r)
      85,000-cleaved fragment of poly(ADP-ribose) polymerase (p85-PARP) using
      immunohistochemistry (IHC). Thirty-two effusions were studied for TrkA, p-TrkA,
      p53, and p21(WAF1/CIP1) expression using immunoblotting. mRNA expression of basic
      fibroblast growth factor (bFGF), interleukin 8, and vascular endothelial growth
      factor (VEGF) was studied in 63 effusions and all solid tumors using in situ
      hybridization. Protein expression of bFGF, interleukin 8, and VEGF was
      additionally studied in 30 effusions using IHC. RESULTS: NGF, TrkA, and p-TrkA
      were expressed in carcinoma cells in effusions in 60 of 80 (75%), 64 of 80 (80%),
      and 15 of 80 (19%) specimens, respectively. In solid tumors, p-TrkA expression
      was more frequent (52 of 65 tumors; 80%) and was accompanied by p-TrkA expression
      in endothelial cells. NGF colocalized with bFGF protein (P = 0.016) and mRNA (P =
      0.032) in effusions, and with VEGF (P < 0.001) and bFGF (P = 0.008) in solid
      tumors. In survival analysis, expression of p85-PARP (P = 0.017) and cytoplasmic
      TrkA (P < 0.001) in effusions predicted better outcome, whereas membrane
      expression of p-TrkA in solid tumors correlated with poor survival (P = 0.004).
      Diffuse expression of p53 and Ki-67 was often seen using IHC, whereas
      p21(WAF1/CIP1) and p85-PARP expression was infrequent and focal. None of these
      correlated with NGF or TrkA expression or activity. CONCLUSIONS: Coexpression of
      NGF with molecules involved in angiogenesis and p-TrkA expression in endothelial
      cells suggest that the proangiogenic role attributed to NGF in vitro and in vivo
      may be relevant in clinical cancer. Expression of p85-PARP as a marker of
      apoptosis and cytoplasmic expression of TrkA (probably representing
      nonglycosylated receptor) predict better outcome, whereas p-TrkA activation
      correlates with poor outcome in advanced stage serous ovarian carcinoma.

PMID- 12796394
TI  - Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1
      promotes progression of non-small cell lung cancer.
AB  - PURPOSE: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) has
      recently been implicated in cancer development and progression. This study was
      performed to assess whether CEACAM-1 expression in primary tumors is correlated
      to long-term survival in patients with operable non-small cell lung cancer
      (NSCLC). EXPERIMENTAL DESIGN: Primary tumors of 145 consecutive patients with
      completely resected NSCLC (pT(1-4) pN(0-2) M(0) R(0)) were stained
      immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2. The
      prognostic relevance of CEACAM-1 expression was evaluated by univariate Kaplan
      Meier and multivariate Cox regression analysis. The median follow-up period was
      72 months (range, 10-130 months). RESULTS: Normal bronchiolar epithelium present
      in all sections exhibited no immunostaining. In contrast, 73 tumors (50.4%)
      showed between 1 and 66% CEACAM-1 positive tumor cells, and 72 tumors (49.6%)
      exhibited even a higher percentage of positive tumor cells. A high CEACAM-1
      expression rate (i.e., >/=66% positive tumor cells) was more frequent in
      adenocarcinomas than in squamous cell carcinomas (61.9 versus 35.7%,
      respectively). Multivariate Cox regression analysis demonstrated that CEACAM-1
      represents an independent prognosticator for cancer-related survival (P = 0.018;
      relative risk, 1.8; 95% confidence interval, 1.1-2.8). Subgroup analysis revealed
      that a high CEACAM-1 expression rate was of significant prognostic impact in
      pN(1)-pN(2) patients (n = 60; P = 0.024), pT(3)-pT(4) patients (n = 22; P =
      0.009), and stage IIa-IIIa patients (n = 69; P = 0.012). CONCLUSIONS: The absence
      of CEACAM-1 in normal lung tissue and its expression in tumor cells argues
      against a tumor-suppressive role of CEACAM-1 in NSCLC. The correlation between
      elevated CEACAM-1 expression and an unfavorable prognosis indicates rather that
      CEACAM-1 might promote lung cancer progression.

PMID- 12796395
TI  - Tumor-specific transcription factor binding to an activator protein-2/Sp1 element
      of the urokinase-type plasminogen activator receptor promoter in a first large
      series of resected gastrointestinal cancers.
AB  - PURPOSE: Evidence for transactivation of genes via specific promoter elements has
      been derived from studies on tumor cell lines but rarely on resected tumors.
      However, the proof of an in vivo relevance and the identification of patients
      with a potential tumor-specific gene expression is essential to transfer
      molecular-targeting strategies into clinical applications. This study gives the
      first clinical evidence that urokinase-type plasminogen activator receptor (u
      PAR) gene expression is tumor-specifically regulated via an activator protein
      (AP)-2/Sp1 promoter element in a large patient subpopulation. EXPERIMENTAL
      DESIGN: In 145 gastrointestinal cancer patients, electrophoretic mobility shift
      analysis and supershift assays for u-PAR-promoter region -152/-135 were performed
      in tumors and corresponding normal tissues. u-PAR protein levels were measured by
      ELISA. RESULTS: Binding of Sp1 to region -152/-135 in tumors in contrast to
      corresponding normal mucosae was observed in 55% of colorectal and in 52% of
      gastric cancer patients. Tumor-specific binding of an AP-2-related factor was
      seen in 59% of colorectal and in 63% of gastric cancer patients. A significant
      correlation between AP-2 (P < 0.0001) and Sp1 (P = 0.0003) binding with a high u
      PAR expression was observed in tumors but not in normal mucosae. Tissues of five
      nontumor patients did not show transcription factor binding to this region.
      CONCLUSIONS: This is the first study to show the tumor-specific binding of trans
      activators to the u-PAR promoter region (-152/-135) biochemically in a large
      series of resected tumors. For the subpopulation of approximately 60% of patients
      with tumor-restricted u-PAR-transactivation, a molecular targeting of this region
      or its activating pathways should be pursued as a new antimetastasis therapy
      approach.

PMID- 12796396
TI  - Frequent HOXA11 and THBS2 promoter methylation, and a methylator phenotype in
      endometrial adenocarcinoma.
AB  - PURPOSE: This study was designed to determine whether there is a methylator
      phenotype in stage I and II endometrioid endometrial adenocarcinoma, and if so,
      whether methylation correlates with recurrence. EXPERIMENTAL DESIGN: Bisulfite
      converted DNAs from 24 stage I and II primary cancers (12 recurrent and 12
      nonrecurrent), and 5 endometrial cancer cell lines were analyzed for methylation
      in the promoter regions of seven genes. A methylation index (MeI) was calculated
      for each tumor. Frequent HOXA11 and THBS2 methylation prompted analysis of case
      matched bloods and 25 additional nonrecurrent primary cancers. Statistical
      analysis included Fisher's exact and Student t tests. RESULTS: Rates of
      methylation in the initial tumor series were as follows: HOXA11, 70.8%; THBS2,
      62.5%; MLH1, 33.3%; CTNNB1, 16.7%; VDR, 4.2%; CDKN2A, 4.2%; and THBS1, 0%. There
      was no difference in the MeI of recurrent and nonrecurrent cases. However, cell
      lines had higher mean MeI. High rates of HOXA11 and THBS2 methylation were
      confirmed in the additional nonrecurrent tumors. None of the 24 case-matched
      bloods had HOXA11 methylation, whereas three blood DNAs showed THBS2 methylation.
      There was a statistically significant difference in the rate of HOXA11
      methylation in recurrent and nonrecurrent tumors (P = 0.0167). CONCLUSIONS:
      Endometrial adenocarcinomas have a methylator phenotype. No correlation between
      MeI and clinicopathologic variables in early stage tumors was observed. High
      rates of methylation were found in the HOXA11 and THBS2 promoter regions. HOXA11
      promoter methylation was significantly more frequent in recurrent than
      nonrecurrent cases. HOXA11 methylation in early stage endometrial cancer is
      associated with poor outcome.

PMID- 12796397
TI  - High expression of steroid sulfatase mRNA predicts poor prognosis in patients
      with estrogen receptor-positive breast cancer.
AB  - PURPOSE: Prognostic significance of the intratumoral mRNA expression of three
      enzymes related to in situ estrogen biosynthesis, i.e., aromatase, sulfatase, and
      17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), was evaluated in
      patients with invasive breast cancer. EXPERIMENTAL DESIGN: Aromatase, sulfatase,
      and 17beta-HSD1 mRNA levels in tumor tissues (n = 181) and normal breast tissues
      (n = 34) were examined by a quantitative, real-time PCR assay and compared with
      various clinicopathological factors as well as prognosis. RESULTS: The sulfatase
      mRNA levels, but not the aromataseor 17beta-HSD1 mRNA levels, were significantly
      associated with lymph node metastases (P < 0.005), histological grade III (P <
      0.001), and poor prognosis (P < 0.005). The association between the sulfatase
      mRNA and poor prognosis was found to be significant (P < 0.001) only in patients
      with estrogen receptor (ER)-positive tumors but not in ER negative tumors. In ER
      positive tumors, the sulfatase mRNA levels was a significant prognostic factor
      independent of the lymph node status and histological grade by multivariate
      analysis. CONCLUSIONS: The sulfatase mRNA levels can serve as a significant,
      independent prognostic factor only in ER-positive tumors. It is speculated that
      the up-regulation of sulfatase mRNA levels leads to a high intratumoral estrogen
      concentration and, thus, an enhanced stimulation of tumor growth through ERs.

PMID- 12796398
TI  - Chromosomal instability detected by fluorescence in situ hybridization in
      surgical specimens of non-small cell lung cancer is associated with poor
      survival.
AB  - PURPOSE: Chromosomal instability (CIN) in non-small cell lung cancer (NSCLC) has
      yet to be well studied. We examined the relationship between CIN detected by
      fluorescence in situ hybridization and survival in patients with NSCLC.
      EXPERIMENTAL DESIGN: Touch preparations from 50 surgical specimens of NSCLC were
      studied. Tumors included 34 adenocarcinomas, 15 squamous cell carcinomas, and 1
      large cell carcinoma. The pathologic stage was IA in 14, IB in 17, IIB in 8, IIIA
      in 9, and IIIB in 2 cases. Enumeration of chromosomes 3, 10, 11, and 17 was used
      to determine which tumors carried CIN. The association between CIN and survival
      was also analyzed. RESULTS: Disomy was most common, but tetrasomy and trisomy of
      the examined chromosomes were seen frequently. Fourteen tumors (28%) showed
      heterogeneity of all four chromosomes examined and were judged to be carrying
      CIN. Both univariate and multivariate analyses revealed that two factors, lymph
      node metastasis and CIN, were significant poor prognostic factors. CONCLUSIONS:
      CIN in NSCLC detected by fluorescence in situ hybridization is an independent
      factor predicting a poor prognosis.

PMID- 12796399
TI  - The role of novel oncogenes squamous cell carcinoma-related oncogene and
      phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral
      tongue.
AB  - PURPOSE: Amplification at chromosome 3q26.3 is a common and crucial event in head
      and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor
      progression and clinical outcome. Two novel oncogenes, namely squamous cell
      carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding
      phosphatidylinositol-3 kinase catalytic alpha-polypeptide), have been identified
      as targets of 3q26.3 amplification. This study aimed to delineate the role of
      SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. EXPERIMENTAL DESIGN: The
      association between gene copy number for SCCRO and PIK3CA measured by
      fluorescence in situ hybridization and level of mRNA expression quantitated by
      real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell
      lines. In addition, gene expression in 49 consecutive primary SCCs of the oral
      tongue was determined and correlated with clinicopathological characteristics and
      outcome. RESULTS: The mRNA level of SCCRO and PIK3CA was significantly correlated
      to the gene copy number in nine HNSCC cell lines. In addition, the expression
      level of SCCRO and PIK3CA was significantly greater in malignant tissues compared
      with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P
      < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of
      patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate
      analyses demonstrated that SCCRO overexpression correlated with nodal metastases
      (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was
      associated with vascular invasion (P = 0.04). Only SCCRO overexpression was
      associated with disease-specific (P = 0.04) and overall survival (P = 0.02).
      Furthermore, SCCRO overexpression remained an independent predictor for cervical
      nodal metastasis on multivariate regression analysis (chi(2) likelihood ratio =
      4.38; P = 0.04). CONCLUSIONS: Although both SCCRO and PIK3CA may play a role in
      the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears
      to be a significant predictor of regional metastasis and may be a marker for
      tumor aggressiveness and clinical outcome.

PMID- 12796400
TI  - Chromosomal instability rather than p53 mutation is associated with response to
      neoadjuvant cisplatin-based chemotherapy in gastric carcinoma.
AB  - PURPOSE: The objective of the study was to evaluate microsatellite alterations
      [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation
      in the p53 gene in relation to response and patient survival to a cisplatin-based
      neoadjuvant chemotherapy in gastric cancer. EXPERIMENTAL DESIGN: Fifty-three
      pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite
      markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for
      mutations by denaturing high-pressure liquid chromatography and sequencing. p53
      protein expression was evaluated by immunohistochemistry. Patients were treated
      with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was
      evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The
      median follow-up of the patients was 45.6 months. RESULTS: p53 mutations were
      identified in 19 of the 53 (36%) analyzed tumors. No significant association with
      response or survival was found for p53 mutation or for p53 protein expression.
      MSI (either high-grade MSI or low-grade MSI) did not show a correlation with
      response. With respect to LOH, LOH at chromosome 17p13 showed a significant
      association with therapy response (P = 0.022) but did not reach statistical
      significance in terms of patient survival. The global LOH rate, expressed as
      fractional allelic loss (FAL), was assessed, and tumors were classified into
      tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A
      statistically significant association of FAL with therapy response was found (P =
      0.003), with a high FAL being related to therapy response. The sensitivity,
      specificity, positive predictive value, and negative predictive value for FAL >
      0.5 were 45%, 93%, 82%, and 72%, respectively. CONCLUSIONS: A high level of
      chromosomal instability (high FAL value) defines a subset of patients who are
      more likely to benefit from cisplatin-based neoadjuvant chemotherapy. p53
      mutation status is not significantly associated with therapy response and is not
      a useful marker for response prediction.

PMID- 12796401
TI  - Response to epidermal growth factor receptor inhibitors in non-small cell lung
      cancer cells: limited antiproliferative effects and absence of apoptosis
      associated with persistent activity of extracellular signal-regulated kinase or
      Akt kinase pathways.
AB  - The epidermal growth factor receptor (EGFR) is an important novel target for
      anticancer therapy. In this study, we examined the molecular mechanisms that
      underlie the antitumor effects of the anti-EGFR monoclonal antibody C225
      (Cetuximab) and the selective EGFR tyrosine kinase inhibitor ZD1839 (Iressa;
      AstraZeneca) in non-small cell lung cancer (NSCLC) cell lines. Cell growth,
      assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay, was inhibited at low concentrations of ZD1839 and C225 in control A431
      cells, whereas the NSCLC cell lines were comparatively more resistant. In A431
      cells, but not in the NSCLC cells, ZD1839 treatment resulted in a modest increase
      in DNA fragmentation, the externalization of phosphatidyl serine, and the
      activation of caspase-3, known markers of apoptotic cell death. However, poly(ADP
      ribose) polymerase cleavage was not detected, and caspase inhibition by
      carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone partially reduced ZD1839-generated
      DNA fragmentation. Overexpression of the antiapoptotic protein Bcl-2 in A431
      cells suppressed the cytotoxicity upon anti-EGFR treatment. These results thus
      demonstrate that the toxic effect of ZD1839 in A431 cells is caused by a form of
      cell death that involves a mitochondrial step and is, at least in part, dependent
      on caspase activation. EGFR expression levels showed no significant correlation
      with sensitivity to ZD1839 and C225. Evaluation of the mitogen-activated protein
      kinase kinase/extracellular signal-regulated kinase and phosphatidylinositol 3'
      kinase/Akt pathways showed considerable inhibition of these pathways by ZD1839
      and C225 in A431 cells, whereas one or both of these pathways remained active
      upon anti-EGFR treatment in NSCLC cells. In addition, treatment with specific
      inhibitors of mitogen-activated protein kinase kinase or phosphatidylinositol 3'
      kinase resulted in a smaller effect on proliferation than simultaneous treatment
      with both inhibitors, whereas induction of apoptosis was observed only when both
      pathways were blocked. Together, these data suggest that persistent activity of
      either of these signaling pathways is involved in the lack of sensitivity of
      NSCLC cell lines to EGFR inhibitors.

PMID- 12796402
TI  - DNA mismatch repair (MMR) mediates 6-thioguanine genotoxicity by introducing
      single-strand breaks to signal a G2-M arrest in MMR-proficient RKO cells.
AB  - PURPOSE: The DNA mismatch repair (MMR) system plays an important role in
      mediating cell death after treatment with various types of chemotherapeutic
      agents, although the molecular mechanisms are not well understood. In this study,
      we sought to determine what signal is introduced by MMR after 6-thioguanine (6
      TG) treatment to signal a G(2)-M arrest leading to cell death. EXPERIMENTAL
      DESIGN: A comparison study was carried out using an isogenic MMR(+) and MMR(-)
      human colorectal cancer RKO cell system, which we established for this study.
      Cells were exposed to 6-TG (3 micro M x 24 h) and then harvested daily for the
      next 3-6 days for growth inhibition assays. Cell cycle effects were determined by
      flow cytometry, and DNA strand breaks were measured using pulsed-field gel
      electrophoresis and alkaline Comet assays. RESULTS: We first established MMR(+)
      RKO cell lines by transfection of human MutL homologue 1 (hMLH1) cDNA into the
      hMLH1-deficient (MMR(-)) RKO cell line. The ectopically expressed hMLH1 protein
      restored a MMR-proficient phenotype in the hMLH1(+) transfectants, showing a
      significantly increased and prolonged G(2)-M arrest followed by cell death after
      6-TG exposure, compared with the vector controls. The MMR-mediated, 6-TG-induced
      G(2)-M arrest started on day 1, peaked on day 3, and persisted to day 6 after 6
      TG removal. We found that DNA double-strand breaks were comparably produced in
      both our MMR(+) and MMR(-) cells, peaking within 1 day of 6-TG treatment. In
      contrast, single-strand breaks (SSBs) were more frequent and longer lived in
      MMR(+) cells, and the duration of SSB formation was temporally correlated with
      the time course of 6-TG-induced G(2)-M arrest. CONCLUSIONS: Our data suggest that
      MMR mediates 6-TG-induced G(2)-M arrest by introducing SSBs to signal a
      persistent G(2)-M arrest leading to enhanced cell death.

PMID- 12796403
TI  - Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes
      improves antitumoral efficacy.
AB  - PURPOSE: Cationic liposomes have been shown to selectively target tumor
      endothelial cells. Therefore, the encapsulation of antineoplastic drugs into
      cationic liposomes is a promising tool to improve selective drug delivery by
      targeting tumor vasculature. It was the aim of our study to evaluate tumor
      selectivity and antitumoral efficacy of paclitaxel encapsulated in cationic
      liposomes in comparison with the free drug paclitaxel (Taxol(R)) in vivo.
      EXPERIMENTAL DESIGN: Experiments evaluating tumor selectivity were carried out in
      male Syrian golden hamsters bearing the amelanotic hamster melanoma A-Mel-3 in
      dorsal skinfold preparations. Growth of tumor cells was observed after s.c.
      inoculation (day 0). On days 5, 7, 9, 12, 14, and 16, animals were treated by
      continuous i.v. infusion over 90 min with 5% glucose, Taxol(R), unloaded cationic
      liposomes, or paclitaxel encapsulated into cationic liposomes (LipoPac),
      respectively (lipid dose, 150 mg/kg body weight; paclitaxel dose, 5 mg/kg body
      weight). Tumor volumes and presence of regional lymph node metastases were
      quantified. RESULTS: Vascular targeting of rhodamine-labeled cationic liposomes
      was maintained after encapsulation of paclitaxel as revealed by in vivo
      fluorescence microscopy (ratio of dye concentration, tumor:normal tissue = 3:1).
      The s.c. tumor growth revealed a remarkable retardation of tumor growth after
      treatment with LipoPac (1.7 +/- 0.3 cm(3)). In contrast, control tumors showed
      exponential tumor growth [tumor volume at the end of the observation period (mean
      +/- SE): 5% glucose, 17.7 +/- 1.9 cm(3); unloaded cationic liposomes, 10.0 +/-
      1.6 cm(3); Taxol(R), 10.7 +/- 1.7 cm(3)]. In addition, the appearance of regional
      lymph node metastases was significantly delayed by treatment with paclitaxel
      encapsulated into cationic liposomes in comparison with all other groups.
      CONCLUSIONS: The data suggest that cationic liposomes are a powerful tool for
      selective and efficient drug delivery to tumor microvessels. This may serve as
      proof of the concept of neovascular tumor targeting therapy by cationic
      liposomes.

PMID- 12796404
TI  - Glial cell-induced endothelial morphogenesis is inhibited by interfering with
      extracellular signal-regulated kinase signaling.
AB  - PURPOSE: Tumor vasculature provides the infrastructure by which malignant tissue
      can be nourished; therefore, targeting angiogenesis may be an effective means of
      treating cancer. We showed previously that SNB19 glioblastoma cells modulate
      bovine retinal endothelial cells in cocultures to form capillary-like network
      structures, that matrix metalloproteinase-9 (MMP-9) expression is critical for
      endothelial morphogenesis, and that MMP-9 expression in glioblastoma cells is
      regulated by extracellular signal-regulated kinase-1 (ERK-1). In the present
      study, we investigated whether interfering with the activation of this mitogen
      activated protein (MAP) kinase would repress MMP-9 synthesis and inhibit
      capillary formation. EXPERIMENTAL DESIGN: Cocultures of bovine retinal
      endothelial and SNB19 cells were analyzed for MMP-9 secretion, and phospho- and
      total ERK levels. These cocultures were treated with PD98059, a specific
      inhibitor of MAP/ERK kinase 1, or transfected with dominant-negative ERK-1 mutant
      containing expression vector. Alterations in capillary-like structure formation,
      and actin cytoskeleton and secretion of vascular endothelial growth factor
      (VEGF), MMP-9, and tissue inhibitor of metalloproteinase-1 were determined by
      immunofluorescence, gelatin zymography, and Western blotting. RESULTS: We found
      that inhibition of the ERK-1/2 pathway with PD98059 abrogated glial cell-mediated
      capillary formation by the endothelial cells and reduced the levels of MMP-9 in
      the coculture. Strikingly, the abrogation of MAP kinase signaling by a dominant
      negative ERK-1 mutant inhibited glial-induced capillary network formation by
      reducing VEGF levels and MMP-9 activity and increasing the levels of tissue
      inhibitor of metalloproteinase-1. Inhibition of ERK activity also disrupted the
      formation of the actin cytoskeleton, a prerequisite for endothelial cell
      migration. CONCLUSION: The mechanism underlying activation of ERK is involved in
      reorganization of the actin cytoskeleton, and induction of VEGF and MMP-9,
      thereby stimulating endothelial cell morphogenesis. These studies clearly provide
      experimental evidence that ERK inhibition diminishes glial-induced endothelial
      cell morphogenesis; therefore, interfering with ERK signaling may be a viable
      approach to target angiogenesis.

PMID- 12796405
TI  - The combination of a potent vitamin D3 analog, EB 1089, with ionizing radiation
      reduces tumor growth and induces apoptosis of MCF-7 breast tumor xenografts in
      nude mice.
AB  - PURPOSE: The purpose of this research was to evaluate theinfluence of the
      combination of the vitamin D(3) analogue EB 1089 with fractionated radiation on
      growth and apoptosis of MCF-7 tumor xenografts in athymic mice. EXPERIMENTAL
      DESIGN: Four to six-week-old ovariectomized mice were injected s.c. with MCF-7
      tumor cells suspended in Matrigel. When tumors reached a size of approximately
      150-200 mm(3), animals were exposed to EB 1089 (45 pmols/day) for 8 days, whereas
      mice that were to be irradiated in the absence of EB 1089 received solvent
      (Solutol HS15). After the termination of EB 1089 and solvent administration,
      tumors were irradiated (3 x 5 Gy) over a period of 3 days using a 300 KV Pantax
      Therapax irradiator. Tumor growth was monitored for 25-30 days after the last
      dose of irradiation in a double-blind manner; tumor cellularity was assessed by
      H&E and trichrome staining, cell proliferation by Ki-67 staining, and apoptosis
      by terminal deoxynucleotidyltransferase-mediated nick end labeling assay. Rates
      of tumor regression were assessed using a mixed effects statistical model.
      RESULTS: A significantly higher rate of decline in tumor volume (7.5% per day)
      was observed in mice exposed to radiation subsequent to EB 1089 compared with
      animals treated with radiation alone (5.6% per day). Final tumor volumes in
      animals irradiated after EB 1089 were approximately 50% lower than in the group
      that received radiation alone. Loss of cellularity, a marked reduction in the
      fraction of proliferating cells, and the promotion of apoptosis confirmed that
      the combination of EB 1089 with radiation was significantly more effective than
      radiation alone in blocking tumor cell growth and promoting tumor cell death.
      CONCLUSIONS: This work demonstrates that EB 1089 can improve local tumor control
      by fractionated radiation, in part through the promotion of apoptotic cell death.

PMID- 12796406
TI  - Intensification of antitumor effect by T helper 1-dominant adoptive immunogene
      therapy for advanced orthotopic colon cancer.
AB  - PURPOSE: T helper (Th) 1/Th2 balance, controlled by Th1 or Th2 cells producing
      cytokines, plays important roles in antitumor immunity. Interleukin-18 (IL-18)
      can act together with IL-12 in promoting the generation of IFN-gamma producing
      Th1 cells. The goal of this study was to determine whether cytotoxic T lymphocyte
      (CTL) secreted in a murine IL-18-induced Th1-dominant state inhibited the
      development of primary tumors and synchronous liver metastases in orthotopic
      colon cancer model. EXPERIMENTAL DESIGN: Murine IL-18 gene was transduced into
      activated T lymphocytes by an adenovirus vector encoding IL-18 (AdIL-18) liposome
      complex method. Efficacy of adoptive immunogene therapy using AdIL-18 with or
      without IL-12 was tested in advanced orthotopic xenograft of murine colon cancer.
      To elucidate the mechanism responsible for the adoptive immunogene therapy, serum
      IL-4, IL-6, IFN-gamma, and tumor necrosis factor alpha production in Th1/Th2
      cytokine balance and quantification of tumor vascularity were investigated.
      RESULTS: By a modified method of adenoviral gene transduction, T lymphocytes
      achieved efficient IL-18 production without cell toxicity. Against orthotopic
      colon cancer, when combined with low dose of recombinant (r) IL-12 (AdIL-18
      CTL/rIL-12), the therapeutic efficacy showed much smaller tumors with no liver
      metastases and no disseminated tumors. There was a significant difference in the
      volume of primary tumors and the number of liver metastases compared with the
      group treated with AdIL-18-CTL alone or other group (P < 0.01). In addition, the
      median survival time of the group treated with AdIL-18-CTL was 53.7 +/- 5.8 days
      and that of AdIL-18-CTL/rIL-12 was 78.4 +/- 6.1 days, which was also a
      significant difference (P < 0.01). These antitumor mechanisms were involved with
      Th1-dominant response in serum Th1/Th2 cytokine balance and suppression of
      neovascularization at primary tumor site. CONCLUSION: These data suggest that a
      strategy of Th1/Th2 balance-based adoptive immunogene therapy might be useful for
      advanced cancer patients.

PMID- 12796407
TI  - Paclitaxel induces apoptosis via protein kinase A- and p38 mitogen-activated
      protein-dependent inhibition of the Na+/H+ exchanger (NHE) NHE isoform 1 in human
      breast cancer cells.
AB  - PURPOSE: The molecular signal components essential to paclitaxel-dependent
      apoptosis in breast cancers are potential targets for combined therapy. However,
      the signal mechanisms underlying paclitaxel action still need to be better
      defined. EXPERIMENTAL DESIGN: In a breast cancer cell line, pharmacological
      agents and transient transfection with dominant interfering and constitutive
      active mutants were used to identify the signal transduction module involved in
      the regulation of paclitaxel-induced apoptosis and to evaluate its potential as a
      therapeutic target. RESULTS: In MDA-MB-435 cells, paclitaxel treatment stimulated
      the activity of both protein kinase A and p38, and inhibited the activity of the
      Na(+)/H(+) exchanger isoform 1 (NHE1) with similar IC(50) concentrations as for
      its activation of apoptosis. Activation and inhibition experiments demonstrated
      that protein kinase A and p38 participate sequentially upstream of the NHE1 in
      regulating the paclitaxel-induced apoptotic pathway. Importantly, concurrent
      specific inhibition of the NHE1 with paclitaxel treatment resulted in a
      synergistic induction of apoptosis and a reduction in the paclitaxel IC(50) for
      apoptosis. This sensitization of paclitaxel apoptotic action by specific
      inhibition of NHE1 was verified in breast cancer cell lines with different
      paclitaxel sensitivity. CONCLUSIONS: We have, for the first time, identified NHE1
      as an essential component of paclitaxel-induced apoptosis in breast cancer cells
      and, importantly, identified that simultaneous inhibition of the NHE1 results in
      a synergistic potentiation of low-dose paclitaxel apoptotic action. As specific
      NHE1 inhibitors have finished Phase II/Phase III clinical trials for myocardial
      protection, there is the possibility for a rapid biological translation of this
      novel therapeutic strategy to a clinical setting.

PMID- 12796408
TI  - Truncated galectin-3 inhibits tumor growth and metastasis in orthotopic nude
      mouse model of human breast cancer.
AB  - PURPOSE: The goal of this research was to evaluate a potential therapeutic agent
      for breast cancer based on galectin-3 that has been implicated in tumorigenicity
      and metastasis of breast cancer. The hypothesis was that therapy with NH(2)
      terminally truncated form of galectin-3 (galectin-3C) will be efficacious for
      reduction in tumor growth and for inhibition of metastases. EXPERIMENTAL DESIGN:
      Recombinant human galectin-3 was produced in Escherichia coli from which galectin
      3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and
      organ biodistribution studies were performed in nude mice. For efficacy studies,
      nude mice bearing orthotopically implanted tumors derived from breast cancer cell
      line MDA-MB-435 were treated with galectin-3C or a vehicle control i.m. twice
      daily for 90 days. RESULTS: The maximum tolerated dose of galectin-3C in nude
      mice was determined to be >125 mg/kg without overt adverse effects. The
      elimination half-life when administered i.m. was found to be 3.0 h in the serum
      and 4.3 h in the cellular fraction of the blood. Organ biodistribution studies
      revealed that galectin-3C localized in the liver, kidneys, and spleen but not in
      the heart or lungs. We found that the mean tumor volumes and weights were
      statistically significantly less in mice treated with galectin-3C compared with
      control mice, and that fewer numbers of mice exhibited lymph node metastases in
      the treated group compared with the control group. CONCLUSIONS: Galectin-3C is
      not overtly toxic, and is efficacious in reducing metastases and tumor volumes
      and weights in primary tumors in an orthotopic nude mouse model of human breast
      cancer.

PMID- 12796409
TI  - Correspondence re: A. Lipton et al., Serum osteoprotegerin levels in healthy
      controls and cancer patients. Clin. Cancer Res., 8: 2306-2310, 2002.

PMID- 12796411
TI  - Heads and hearts: the endothelial connection.

PMID- 12796412
TI  - Adding to the effectiveness of intravenous tissue plasminogen activator for
      treating acute stroke.

PMID- 12796413
TI  - Perioperative cardiac assessment for noncardiac surgery: eight steps to the best
      possible outcome.

PMID- 12796414
TI  - Current perspectives on arterial stiffness and pulse pressure in hypertension and
      cardiovascular diseases.

PMID- 12796415
TI  - Images in cardiovascular medicine. Polyarteritis nodosa inducing symmetric
      peripheral gangrene.

PMID- 12796416
TI  - Images in cardiovascular medicine. Unusual manifestation of Libman-Sacks
      endocarditis in systemic lupus erythematosus.

PMID- 12796417
TI  - Chlamydia pneumoniae, antibiotic treatment, and early atherosclerosis.

PMID- 12796418
TI  - Serum levels of interleukin-18--a potential marker of cardiovascular death--could
      be determined by genetic predisposition.

PMID- 12796419
TI  - Left ventricular remodeling after valve replacement in patients with isolated
      aortic regurgitation.

PMID- 12796420
TI  - Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation.

PMID- 12796421
TI  - Endothelin receptor blockade and exacerbation of heart failure.

PMID- 12796422
TI  - Thermography to detect inflamed macrophage-rich plaques.

PMID- 12796423
TI  - B-natriuretic peptide and left ventricular ejection fraction are complementary
      predictors.

PMID- 12796424
TI  - It is immoral to require consent for cadaver organ donation.

PMID- 12796425
TI  - Death, us and our bodies: personal reflections.

PMID- 12796426
TI  - Organ procurement: dead interests, living needs.

PMID- 12796427
TI  - Cadaveric tissue donation: a pathologist's perspective.

PMID- 12796428
TI  - An ethical market in human organs.

PMID- 12796429
TI  - Is the sale of body parts wrong?

PMID- 12796430
TI  - Commentary. An ethical market in human organs.

PMID- 12796432
TI  - Commodification and exploitation: arguments in favour of compensated organ
      donation.
AB  - This paper takes the view that compensated donation and altruism are not
      incompatible. In particular, it holds that the arguments against giving
      compensation stand on weak rational grounds: (1) the charge that compensation
      fosters "commodification" has neither been specific enough to account for
      different types of monetary transactions nor sufficiently grounded in reality to
      be rationally convincing; (2) although altruism is commendable, organ donors
      should not be compelled to act purely on the basis of altruistic motivations,
      especially if there are good reasons to believe that significantly more lives can
      be saved and enhanced if incentives are put in place, and (3) offering
      compensation for organs does not necessarily lead to exploitation-on the
      contrary, it may be regarded as a necessity in efforts to minimise the level of
      exploitation that already exists in current organ procurement systems.

PMID- 12796433
TI  - Presumed consent for transplantation: a dead issue after Alder Hey?
AB  - In the wake of scandals about the unauthorised retention of organs following
      postmortem examination, the issue of valid consent (or the lack of it) has
      returned to the forefront. Emphasis is put on obtaining explicit authorisation
      from the patient or family prior to any medical intervention, including those
      involving the dead. Although the controversies in the UK arose from the retention
      of human material for education or research rather than therapy, concern has been
      expressed that public mistrust could also adversely affect organ donation for
      transplantation. At the same time, however, the British Medical Association (BMA)
      continues to call for a shift to a system of presumed consent for organ
      transplantation. This apparent inconsistency can be justified because valid
      distinctions exist between the reasons requiring explicit consent for retention
      and the acceptability of presumed consent for transplantation. This paper argues
      for introducing a system of presumed consent for organ donation, given the
      overwhelming expressions of public support for transplantation. Ongoing
      legislative review in the UK provides an ideal chance to alter the default
      position to one where potential donors can simply acquiesce or opt out of
      donation. Combined with consultation with their relatives, this could be a much
      better method of realising individuals' wishes. It would also achieve a better
      balance between the duties owed to the deceased and those owed to people awaiting
      a transplant.

PMID- 12796434
TI  - Do the sick have a right to cadaveric organs?
AB  - One way of increasing the supply of organs for transplantation is to adopt a
      policy giving the sick a right to cadaveric organs. Such a right would entail the
      coercive transfer of organs from the dead without their previous consent. Because
      this policy would violate individual autonomy and the special relation between
      humans and their bodies, it would be morally unjustifiable. Although a rights
      based non-consensual model of salvaging cadaveric organs would be medically
      desirable, a communitarian-based consensual model would be a morally justifiable
      alternative way of addressing the problem of organ scarcity.

PMID- 12796435
TI  - Modified mandated choice for organ procurement.
AB  - Presumed consent to organ donation looks increasingly unlikely to be a palatable
      option for increasing organ procurement in the UK following the publication of
      the report into events at Alder Hey and elsewhere. Yet, given that the
      alternative to increasing the number of cadaveric organs available is either to
      accept a greater number of live donations, or accept that people will continue to
      die for the want of an organ, public policy makers remain obliged to consider
      other means of increasing the procurement rate. In this paper, we meet the main
      objections to mandated choice (namely that it undermines autonomy and that
      mandated donation is preferable). We have modified the traditional approach to
      mandated choice to take into account the force of the objection that mandated
      donation is preferable, by accepting that people can and do make bad decisions
      about organ donation and proposing that all accompanying public education and
      information about cadaveric donation should be directed in favour of donation.

PMID- 12796436
TI  - What's not wrong with conditional organ donation?
AB  - In a well known British case, the relatives of a dead man consented to the use of
      his organs for transplant on the condition that they were transplanted only into
      white people. The British government condemned the acceptance of racist offers
      and the panel they set up to report on the case condemned all conditional offers
      of donation. The panel appealed to a principle of altruism and meeting the
      greatest need. This paper criticises their reasoning. The panel's argument does
      not show that conditional donation is always wrong and anyway overlooks a crucial
      distinction between making an offer and accepting it. But even the most
      charitable reinterpretation of the panel's argument does not reject selective
      acceptance of conditional offers. The panel's reasoning has no merit.

PMID- 12796437
TI  - Brain donation for schizophrenia research: gift, consent, and meaning.
AB  - The Neuroscience Institute of Schizophrenia and Allied Disorders's (NISAD) "Gift
      of Hope" Tissue Donor Program is a volunteer programme for people who wish to
      donate their brain when they die for neuroscience research into schizophrenia.
      Organ donation for purposes of research differs from transplant donation in a
      number of ways, most notably the absence of a single recipient. Within a
      particular community, however, (people with schizophrenia and their carers) the
      single recipient is replaced by a sense of shared experience and preventing
      suffering in others. Donors have an investment in the research.

PMID- 12796438
TI  - Unrelated living organ donation: ULTRA needs to go.

PMID- 12796439
TI  - Human organs from prisoners: kidneys for life.
AB  - A proposal to allow prisoners to save their lives or to be eligible for
      commutation of sentence by donating kidneys for transplantation has been a
      subject of controversy in the Philippines. Notwithstanding the vulnerabilities
      associated with imprisonment, there are good reasons for allowing organ donations
      by prisoners. Under certain conditions, such donations can be very beneficial not
      only to the recipients but to the prisoners themselves. While protection needs to
      be given to avoid coercion and exploitation, overprotection has to be avoided.
      The prohibition on the involvement of prisoners in organ transplantation
      constitutes unjustified overprotection. Under certain conditions, prisoners can
      make genuinely independent decisions. When it can be reasonably ascertained that
      they are able to decide freely, society should recognise an obligation to help
      them implement their decisions, such as when they intend to donate an organ as a
      way of asserting their religious faith and performing a sacrifice in atonement
      for their sins.

PMID- 12796440
TI  - A volunteer to be killed for his organs.

PMID- 12796441
TI  - Non-heart beating organ donation: old procurement strategy--new ethical problems.
AB  - The imbalance between supply of organs for transplantation and demand for them is
      widening. Although the current international drive to re-establish procurement
      via non-heart beating organ donation/donor (NHBOD) is founded therefore on
      necessity, the process may constitute a desirable outcome for patient and family
      when progression to brain stem death (BSD) does not occur and conventional organ
      retrieval from the beating heart donor is thereby prevented. The literature
      accounts of this practice, however, raise concerns that risk jeopardising
      professional and public confidence in the broader transplant programme. This
      article focuses on these clinical, ethical, and legal issues in the context of
      other approaches aimed at increasing donor numbers. The feasibility of
      introducing such an initiative will hinge on the ability to reassure patients,
      families, attendant staff, professional bodies, the wider public, law enforcement
      agencies, and the media that practitioners are working within explicit guidelines
      which are both ethically and legally defensible.

PMID- 12796442
TI  - Defining death in non-heart beating organ donors.
AB  - Protocols for retrieving vital organs in consenting patients in cardiovascular
      arrest (non-heart beating donors, NHBD) rest on the assumptions that irreversible
      asystole a) identifies the instant of biological death, and b) is clinically
      assessable at the time when retrieval of vital organs is possible. Unfortunately
      both assumptions are flawed. We argue that traditional life/death definitions
      could be actually inadequate to represent the reality of dying under intensive
      support, and we suggest redefining NHBD protocols on moral, social, and
      anthropological criteria, admitting that irreversible (however defined) asystole
      can only equate a clinically determinable point of no return in the process of
      dying, where organ retrieval can be morally and socially accepted in previously
      consenting patients.

PMID- 12796443
TI  - Attitudes of Swedes to marginal donors and xenotransplantation.
AB  - The aim of our survey was to capture the attitudes of Swedes to marginal donors
      and xenotransplantation. Modern biotechnology makes it possible to replace non
      functioning organs, cells, and genes. Nonetheless, people may have reservations
      and fears about such treatments. With the survey, Attitudes of the General Public
      to Transplants, we have sought to expose the ambivalence that arises when medical
      possibilities are juxtaposed with ideas of risk. The design of the questionnaire
      originates from the interdisciplinary cooperation between ethnologists, medical
      scientists, and geneticists. By combining qualitative and quantitative methods,
      it is possible to illustrate the complexity that characterises people's view of
      modern biomedicine. People's reflections are based on a personal and situation
      bound morality, which does not necessarily coincide with what they generally
      consider as ethically justifiable.

PMID- 12796444
TI  - The altruistic act of asking.
AB  - There are a number of obstacles to increasing the supply of cadaveric organs for
      transplantation. These include reluctance on the part of relatives to agree to
      the so called harvesting of organs from their deceased relative, and the
      unwillingness of some doctors to approach grieving families and ask consent for
      this harvesting to take place. In this paper I will focus on the altruistic act
      of asking that the latter entails, and will argue that failure to acknowledge the
      personal cost of this act to physicians is having an adverse impact on the supply
      of organs. I will draw analogies with the almost equally neglected altruistic act
      of undertaking anatomy dissection and all of the related breaking of societal
      taboos. I will examine the language used in discussions about increasing organ
      supply and conclude that the terms cadaveric and harvest are unhelpful in gaining
      public confidence. A process and vocabulary that openly acknowledges and
      validates the altruistic acts demanded of all the human beings involved--donors,
      recipients, their respective relatives, and the health professionals who mediate
      between them--is needed if the supply of organs is to be increased.

PMID- 12796445
TI  - A stronger policy of organ retrieval from cadaveric donors: some ethical
      considerations.
AB  - Taking organs from dead people seems, prima facie, to raise fewer ethical
      complications than taking organs from other sources. There are, however, serious
      ethical problems in taking organs from the dead unless there is premortem
      evidence that this is what the deceased would have wanted, or at least, not have
      objected to. In this paper we will look at a "strong" opting out policy as
      proposed by John Harris. We will argue that people can be harmed after their
      death and that the posthumous removal of organs against their expressed wishes is
      one form that such harm might take. We also argue that Harris's claim that we
      show "equality of concern" between the donor and recipient requires too much.

PMID- 12796446
TI  - A definition of human death should not be related to organ transplants.

PMID- 12796447
TI  - Affinity proteomics for systematic protein profiling of chromosome 21 gene
      products in human tissues.
AB  - Here we show that an affinity proteomics strategy using affinity-purified
      antibodies raised against recombinant human protein fragments can be used for
      chromosome-wide protein profiling. The approach is based on affinity reagents
      raised toward bioinformatics-designed protein epitope signature tags
      corresponding to unique regions of individual gene loci. The genes of human
      chromosome 21 identified by the genome efforts were investigated, and the success
      rates for de novo cloning, protein production, and antibody generation were 85,
      76, and 56%, respectively. Using human tissue arrays, a systematic profiling of
      protein expression and subcellular localization was undertaken for the putative
      gene products. The results suggest that this affinity proteomics strategy can be
      used to produce a proteome atlas, describing distribution and expression of
      proteins in normal tissues as well as in common cancers and other forms of
      diseased tissues.

PMID- 12796449
TI  - Life, death and membrane bilayers.
AB  - Membrane bilayers are essential elements of life, and the synthesis of the
      hydrocarbons that make up membrane bilayers may have preceded the appearance of
      life on Earth. Membrane-associated processes are significant components of
      metabolism, and the acyl composition of membrane bilayers is associated with
      metabolic activity in a predictable manner. This has resulted in the "membrane
      pacemaker" theory of metabolism, which proposes that the relative balance between
      monounsaturated and long-chain polyunsaturated acyl chains in membrane bilayers
      is a fundamental determinant of metabolic rate of a species. The omega-3
      polyunsaturated docosahexaenoate is an especially important component of
      membranes in this regard. Whilst it is suggested that the physical properties of
      membrane polyunsaturates are important with respect to their influence on
      metabolic rate, it is their chemistry that is important in aging. Membrane acyl
      composition is related to maximum lifespan in mammals and birds, probably via
      their role in lipid peroxidation. Calorie restriction modifies acyl composition
      of membrane bilayers and is associated with decreased membrane lipid peroxidation
      and lifespan extension. The membrane pacemaker theory of metabolism has given
      birth to the membrane pacemaker hypothesis of aging, which will require further
      investigation.

PMID- 12796450
TI  - A family of vortex wakes generated by a thrush nightingale in free flight in a
      wind tunnel over its entire natural range of flight speeds.
AB  - In view of the complexity of the wing-beat kinematics and geometry, an important
      class of theoretical models for analysis and prediction of bird flight
      performance entirely, or almost entirely, ignores the action of the wing itself
      and considers only the resulting motions in the air behind the bird. These
      motions can also be complicated, but some success has previously been recorded in
      detecting and measuring relatively simple wake structures that can sometimes
      account for required quantities used to estimate aerodynamic power consumption.
      To date, all bird wakes, measured or presumed, seem to fall into one of two
      classes: the closed-loop, discrete vortex model at low flight speeds, and the
      constant-circulation, continuous vortex model at moderate to high speeds. Here,
      novel and accurate quantitative measurements of velocity fields in vertical
      planes aligned with the freestream are used to investigate the wake structure of
      a thrush nightingale over its entire range of natural flight speeds. At most
      flight speeds, the wake cannot be categorised as one of the two standard types,
      but has an intermediate structure, with approximations to the closed-loop and
      constant-circulation models at the extremes. A careful accounting for all
      vortical structures revealed with the high-resolution technique permits
      resolution of the previously unexplained wake momentum paradox. All the measured
      wake structures have sufficient momentum to provide weight support over the
      wingbeat. A simple model is formulated and explained that mimics the correct,
      measured balance of forces in the downstroke- and upstroke-generated wake over
      the entire range of flight speeds. Pending further work on different bird
      species, this might form the basis for a generalisable flight model.

PMID- 12796451
TI  - Heat-shock response and temperature resistance in the deep-sea vent shrimp
      Rimicaris exoculata.
AB  - The shrimp Rimicaris exoculata swarms around hydrothermal black smoker chimneys
      at most vent sites along the Mid-Atlantic Ridge. This species maintains close
      proximity to the hydrothermal fluid, where temperatures can reach 350 degrees C
      and steep thermal and chemical gradients are expected. We performed in vivo
      experiments in pressurized aquaria to determine the upper thermal limit [critical
      thermal maximum (CT(max))] of R. exoculata and to investigate some
      characteristics of the shrimp stress response to heat exposure. These experiments
      showed that the shrimp does not tolerate sustained exposure to temperatures in
      the 33-37 degrees C range (CT(max)). A heat-inducible stress protein belonging to
      the hsp70 family was identified in R. exoculata, and its synthesis threshold
      induction temperature is below 25 degrees C. The R. exoculata optimal thermal
      habitat may thus be restricted to values lower than previously expected (<25
      degrees C).

PMID- 12796452
TI  - Effects of social interaction on the electric organ discharge in a mormyrid fish,
      Gnathonemus petersii (Mormyridae, Teleostei).
AB  - African weakly discharging electric fish (Mormyridae) use their self-generated
      electric signals and electroreceptive abilities for orientation and communication
      in the context of courtship and territorial interactions. This paper documents
      socially mediated changes in the electric organ discharge (EOD) of subadult
      Gnathonemus petersii under non-breeding environmental conditions. Increases in
      EOD duration and changes in the relative phase amplitudes occurred in dominant
      fish during same-sex (male-male, female-female) and opposite-sex interactions.
      Similar changes were also observed in fish that were restricted in their physical
      interactions, suggesting that direct contact is not necessary to induce dominance
      typical EOD waveforms. The possible communicative functions of these changes are
      discussed.

PMID- 12796453
TI  - The role of eukaryotic initiation factor 2alpha during the metabolic depression
      associated with estivation.
AB  - We have investigated the role of eukaryotic initiation factor 2alpha (eIF2alpha)
      in two estivating organisms previously shown to downregulate protein synthesis
      during metabolic depression, the land snail Helix aspersa Muller and the desert
      frog Neobatrachus sutor Main 1957. We have developed a method using a single
      antibody (which binds specifically to the phosphorylated, conserved
      phosphorylation region) by which the total levels of eIF2alpha and the ratio of
      phosphorylated eIF2alpha [eIF2alpha(P)] to total (phosphorylated and
      unphosphorylated) eIF2alpha can be determined. In H. aspersa, we have shown that
      the level of eIF2alpha mRNA expression is unchanged between the awake and
      estivating states. The amount of total eIF2alpha is the same in the estivating
      and awake states, and eIF2alpha(P) is undetectable and must represent < or =10%
      of total eIF2alpha in both states. Conversely, in N. sutor during estivation, the
      level of total eIF2alpha increases approximately 1.6-fold and the ratio of
      eIF2alpha(P)/eIF2alpha increases from 0.22+/-0.11 to 0.52+/-0.08, implicating
      eIF2alpha phosphorylation in the downregulation of protein synthesis during
      estivation in this animal. The differences in the amounts of eIF2alpha and the
      level of its phosphorylation between these two species also suggest possible
      differences either in the mechanism by which protein synthesis is downregulated
      during estivation or in the sensitivity of the initiation of translation to
      eIF2alpha(P) levels.

PMID- 12796454
TI  - Food supplements modulate changes in leucocyte numbers in breeding male ground
      squirrels.
AB  - Immunosuppression may be an important cost of reproduction in breeding males. It
      can result from elevated levels of testosterone or stress hormones and may serve
      to lower the energetic cost of maintaining immune function at a time of high
      demand. This suggests that greater access to energy resources could reduce
      immunosuppression as a cost of reproduction, minimizing the trade-off between
      energetic investment in current reproductive effort and survival. I examined the
      impact of food availability on immune function by provisioning male Belding's
      ground squirrels in the field from the time they emerged from hibernation to the
      start of breeding. Temporal changes in immune status, measured by leucocyte
      counts, differed between provisioned males and un-provisioned controls.
      Provisioning advanced the increase in lymphocytes and neutrophils from after
      breeding to before. At the start of breeding, the leucocyte count was three times
      greater in provisioned males than in controls and was still nearly twice as great
      at the end of breeding. Control males increased all leucocyte numbers after
      breeding. This experiment demonstrates that variation in food intake can lead to
      individual variation in the extent of immunosuppression during breeding and
      therefore that reduced immune function may not be an obligatory cost of
      reproduction.

PMID- 12796455
TI  - Sweeping and striking: a kinematic study of the trunk during prey capture in
      three thamnophiine snakes.
AB  - The trunk plays an obvious and important role in the prey capture behavior of
      many species of snake, yet trunk function during predatory strikes is poorly
      understood. Axial kinematics of three thamnophiine snakes (Thamnophis couchii,
      Thamnophis elegans and Nerodia rhombifer) were studied to quantify differences
      between sideways-directed and forward-directed attacks and to investigate strike
      diversity at relatively low phylogenetic levels. Feeding strikes were filmed at
      60 Hz, and 13 points along the head and body were digitized. These points were
      used to calculate body segment displacement, rotation and velocity during
      predatory strikes. Kinematic analysis revealed significant differences in the
      foraging modes of these aquatic-feeding species. T. couchii displayed a
      stereotypical pre-strike posture in which the entire body was arranged in a
      series of loops directed towards the prey. Forward displacement of body segments
      sometimes occurred over the entire body in T. couchii but was restricted to the
      anterior one-third of the trunk in T. elegans and N. rhombifer. T. couchii and N.
      rhombifer both struck rapidly compared with T. elegans, although N. rhombifer
      typically had a short strike distance. N. rhombifer struck significantly faster
      than T. elegans. Aquatic prey capture diversity appears to reflect ecological
      diversity in thamnophiine snakes.

PMID- 12796456
TI  - The spectral input to honeybee visual odometry.
AB  - Bees returning from a feeder placed in a narrow tunnel that is lined with a
      chequered pattern will strongly overestimate travel distance. This finding
      supports the view that their distance estimation is based on integrating optic
      flow experienced during flight. Here, we use chequered tunnels with various
      colour combinations as a tool to identify the spectral channel used by bees to
      gauge travel distance. The probability of bees performing waggle dances after a
      short travel distance correlates only with the low range of the green contrast of
      the pattern in the tunnel. But it does not correlate with the pattern's chromatic
      contrast or brightness contrast. Distance estimation is therefore colour blind.
      We also evaluated the waggle runs as a function of colour pattern. Their duration
      is the code for the food source distance. Waggle run duration is entirely
      independent of the colour pattern used, implying that once green contrast is
      above detection threshold, distance estimation depends solely on the angular
      motion of the landscape passed in flight.

PMID- 12796457
TI  - Evolution of thermotolerance and the heat-shock response: evidence from
      inter/intraspecific comparison and interspecific hybridization in the virilis
      species group of Drosophila. I. Thermal phenotype.
AB  - Species in the virilis group of Drosophila (fruit flies), which overlap or
      replace one another along climatic gradients, exhibit corresponding differences
      in basal thermotolerance, inducible thermotolerance and the heat-shock response.
      The low-latitude species D. virilis exceeds the high-latitude species D. lummei
      in these measures of thermotolerance, the temperature threshold for heat-shock
      factor (HSF) activation and the ability to express hsp70 mRNA and diverse heat
      shock proteins (e.g. Hsp70, Hsp83 and small Hsps) after intense heat shock (e.g.
      40-41 degrees C). The xeric species D. novamexicana differs from the mesic
      species D. texana in much the same way for many of these traits. By contrast,
      intraspecific variation in these traits is small. Because D. virilis and D.
      lummei can readily be crossed to yield partially fertile progeny, genetic
      analysis of interspecific differences is possible. Interspecific hybrids are
      intermediate to the parental species in basal thermotolerance and inducible
      thermotolerance and resemble D. virilis in Hsp concentrations after intense heat
      shock and Hsp70 protein electromorphs.

PMID- 12796458
TI  - Structural colouration of avian skin: convergent evolution of coherently
      scattering dermal collagen arrays.
AB  - Structural colours of avian skin have long been hypothesized to be produced by
      incoherent (Rayleigh/Tyndall) scattering. We investigated the colour, anatomy,
      nanostructure and biophysics of structurally coloured skin, ramphotheca and
      podotheca from 31 species of birds from 17 families in 10 orders from across
      Aves. Integumentary structural colours of birds include ultraviolet, dark blue,
      light blue, green and yellow hues. The discrete peaks in reflectance spectra do
      not conform to the inverse fourth power relationship predicted by Rayleigh
      scattering. The dermis of structurally coloured skin consists of a thick (100-500
      micro m) layer of collagen that is usually underlain by a layer of melanin
      granules. Transmission electron micrographs (TEMs) of this colour-producing
      dermal collagen layer revealed quasi-ordered arrays of parallel collagen fibres.
      Two-dimensional (2-D) Fourier analysis of TEMs of the collagen arrays revealed a
      ring of peak spatial frequencies in the spatial variation in refractive index
      that are the appropriate size to make the observed ultraviolet-yellow colours by
      coherent scattering alone. One species, Philepitta castanea (Eurylaimidae), has
      exceptionally ordered, hexagonal arrays of collagen fibres that produce a
      hexagonal pattern of spatial frequency peaks in the power spectra. Ultraviolet,
      blue, green and yellow structural colours of avian skin are produced by coherent
      scattering (i.e. constructive interference) by arrays of collagen fibres in the
      dermis. Some yellow and orange skin colours are produced with a combination of
      structural and pigmentary mechanisms. These combined colours can have reflectance
      spectra with discrete peaks that are more saturated than hues produced by
      carotenoid pigments alone. Bluish facial skin from two species of Neotropical
      antbirds (Thamnophilidae) are nanostructurally too small to produce visible light
      by coherent scattering, and the colour production mechanism in these species
      remains unknown. Based on the phylogenetic distribution of structurally coloured
      skin in Aves, this mechanism of colour production has evolved convergently more
      than 50 independent times within extant birds.

PMID- 12796459
TI  - Are uniform regional safety factors an objective of adaptive modeling/remodeling
      in cortical bone?
AB  - It has been hypothesized that a major objective of morphological adaptation in
      limb-bone diaphyses is the achievement of uniform regional safety factors between
      discrete cortical locations (e.g. between cranial and caudal cortices at mid
      diaphysis). This hypothesis has been tested, and appears to be supported in the
      diaphyses of ovine and equine radii. The present study more rigorously examined
      this question using the equine third metacarpal (MC3), which has had functionally
      generated intracortical strains estimated by a sophisticated finite element
      model. Mechanical properties of multiple mid-diaphyseal specimens were evaluated
      in both tension and compression, allowing for testing of habitually tensed or
      compressed regions in their respective habitual loading mode ("strain-mode
      specific" loading). Elastic modulus, and yield and ultimate strength and strain,
      were correlated with in vivo strain data from a previously published finite
      element model. Mechanical tests revealed minor variations in elastic modulus, and
      yield and ultimate strength in both tension and compression loading, while
      physiological strains varied significantly between the cortices. Contrary to the
      hypothesis of uniform safety factors, the MC3 has a broad range of tension (caudo
      medial, 4.0; cranio-lateral, 37.7) and compression (caudo-medial, 5.7; cranio
      lateral, 68.9) safety factors.

PMID- 12796460
TI  - Food transport in the C. elegans pharynx.
AB  - Pumping of the C. elegans pharynx transports food particles (bacteria)
      posteriorly. We examined muscle motions to determine how this posterior transport
      is effected. We find that the motions of the middle section of the pharynx, the
      anterior isthmus, are delayed relative to the anterior section, the corpus.
      Simulations in which particles are assumed to move at mean fluid velocity when
      not captured by the walls of the pharyngeal lumen show that delayed isthmus
      motions do indeed cause net particle transport; however, the amount is much less
      than in the real pharynx. We propose that the geometry of the pharyngeal lumen
      forces particles to the center, where they move faster than mean fluid velocity.
      When this acceleration is incorporated into the simulation, particles are
      transported efficiently. The transport mechanism we propose explains past
      observations that the timing of muscle relaxation is important for effective
      transport. Our model also makes a prediction, which we confirm, that smaller
      bacteria are better food sources for C. elegans than large ones.

PMID- 12796461
TI  - Effects of the local mechanical environment on vertebrate tissue differentiation
      during repair: does repair recapitulate development?
AB  - The local mechanical environment is a crucial factor in determining cell and
      tissue differentiation during vertebrate skeletal development and repair. Unlike
      the basic response of bone to mechanical load, as described in Wolff's law, the
      mechanobiological relationship between the local mechanical environment and
      tissue differentiation influences everything from tissue type and molecular
      architecture to the formation of complex joints. This study tests the hypothesis
      that precisely controlled mechanical loading can regulate gene expression, tissue
      differentiation and tissue architecture in the adult skeleton and that precise
      manipulation of the defect's local mechanical environment can initiate a limited
      recapitulation of joint tissue development. We generated tissue type predictions
      using finite element models (FEMs) interpreted by published mechanobiological
      fate maps of tissue differentiation. The experiment included a custom-designed
      external fixator capable of introducing daily bending, shear or a combination of
      bending and shear load regimens to induce precisely controlled mechanical
      conditions within healing femoral defects. Tissue types and ratios were
      characterized using histomorphometrics and molecular markers. Tissue molecular
      architecture was quantified using polarized light and Fourier transforms, while
      immunological staining and in situ hybridization were used to characterize gene
      expression. The finite element models predicted the differentiation of cartilage
      within the defects and that substantial fibrous tissues would develop along the
      extreme excursion peripheries in the bending group. The three experimentally
      induced loading regimens produced contiguous cartilage bands across all
      experimental defects, inhibiting bony healing. Histomorphometric analysis of the
      ratios of cartilage to bone in the experimental groups were not significantly
      different from those for the knee joint, and Fourier transform analysis
      determined significantly different collagen fibril angle specializations within
      superficial, intermediate and deep layers of all experimental cartilages
      (P<0.0001), approximating those for articular cartilage. All stimulations
      resulted in the expression of collagen type II, while the bending stimulation
      also resulted in the expression of the joint-determining gene GDF-5. These
      findings indicate that the local mechanical environment is an important regulator
      of gene expression, tissue differentiation and tissue architecture.

PMID- 12796462
TI  - The swamp eel Monopterus albus reduces endogenous ammonia production and
      detoxifies ammonia to glutamine during 144 h of aerial exposure.
AB  - The swamp eel Monopterus albus inhabits muddy ponds, swamps, canals and rice
      fields, where it can burrow within the moist earth during the dry summer season,
      thus surviving for long periods without water. This study aimed to elucidate the
      strategies adopted by M. albus to defend against endogenous ammonia toxicity when
      kept out of water for 144 h (6 days). Like any other fish, M. albus has
      difficulties in excreting ammonia during aerial exposure. In fact, the rates of
      ammonia and urea excretions decreased significantly in specimens throughout the
      144 h of aerial exposure. At 144 h, the ammonia and urea excretion rates
      decreased to 20% and 25%, respectively, of the corresponding control values.
      Consequently, ammonia accumulated to high levels in the tissues and plasma of the
      experimental specimens. Apparently, M. albus has developed relatively higher
      ammonia tolerance at the cellular and subcellular levels compared with many other
      teleost fish. Since the urea concentration in the tissues of specimens exposed to
      air remained low, urea synthesis was apparently not adopted as a strategy to
      detoxify endogenous ammonia during 144 h of aerial exposure. Instead, ammonia
      produced through amino acid catabolism was detoxified to glutamine, leading to
      the accumulation of glutamine in the body during the first 72 h of aerial
      exposure. Complementing the increased glutamine formation was a significant
      increase in glutamine synthetase activity in the liver of specimens exposed to
      air for 144 h. Formation of glutamine is energetically expensive. It is probably
      because M. albus remained relatively inactive on land that the reduction in
      energy demand for locomotory activity facilitated its exploitation of glutamine
      formation to detoxify endogenous ammonia. There was a slight decrease in the
      glutamine level in the body of the experimental animals between 72 h and 144 h of
      aerial exposure, which indicates that glutamine might not be the end product of
      nitrogen metabolism. In addition, these results suggest that suppression of
      endogenous ammonia production, possibly through reductions in proteolysis and
      amino acid catabolism, acts as the major strategy to avoid ammonia intoxication
      in specimens exposed to air for >/=72 h. It is concluded that glutamine formation
      and reduction in ammonia production together served as effective strategies to
      avoid the excessive accumulation of ammonia in the body of M. albus during 144 h
      of aerial exposure. However, these strategies might not be adequate to sustain
      the survival of M. albus in the mud for longer periods during drought because
      ammonia and glutamine concentrations had already built up to high levels in the
      body of specimens exposed to air for 144 h.

PMID- 12796463
TI  - Central circuitry in the jellyfish Aglantha digitale IV. Pathways coordinating
      feeding behaviour.
AB  - The hydromedusan jellyfish Aglantha digitale feeds on small planktonic organisms
      carried to the margin by tentacle flexions. During feeding, the manubrium bends
      across ("points") and seizes the prey with flared lips. In immobilized
      preparations, pointing to a source of electrical stimulation was accurate, 70% of
      the time, to within 15 degrees. Cutting experiments showed that the conduction
      pathways concerned with pointing and lip flaring are located in eight radial
      strands consisting of a radial canal, a giant nerve axon and a bundle of small
      axons with FMRFamide-like immunoreactivity. Application of food juices to sites
      on the margin and tentacles evoked trains of impulses in the axon bundles (F
      events; conduction velocity 15.5+/-3.7 cm s(-1)) and in the epithelium lining the
      radial canals (E events; conduction velocity 28.5+/-3.5 cm s(-1)). Impulses were
      conducted circularly in the outer nerve ring (F events) or in the ring canal (E
      events). Unilateral flexions of the manubrium during pointing arise from
      preferential excitation of one or more of eight longitudinal "muscle bands" in
      the wall of the manubrium and peduncle. Lip flaring represents symmetrical
      contraction of all eight bands. Cutting experiments revealed that F events
      mediate pointing; E events mediate lip flaring. Thus the endodermal radial
      canals, which in other hydromedusae mediate protective 'crumpling', provide the
      conduction pathway for manubrial lip flaring. Aglantha's alternative protective
      response--escape swimming--makes crumpling unnecessary, releasing the pathway for
      use in feeding. Trains of E events, generated in the manubrium during ingestion,
      propagate to the margin and inhibit rhythmic (slow) swimming with a duration that
      depended on their number and frequency. Inhibition of swimming appeared to
      facilitate transfer of food from the margin to the mouth, but how it comes about
      is unclear.

PMID- 12796464
TI  - cGMP-dependent changes in phototaxis: a possible role for the foraging gene in
      honey bee division of labor.
AB  - Division of labor in honey bee colonies is influenced by the foraging gene
      (Amfor), which encodes a cGMP-dependent protein kinase (PKG). Amfor upregulation
      in the bee brain is associated with the age-related transition from working in
      the hive to foraging for food outside, and cGMP treatment (which increases PKG
      activity) causes precocious foraging. We present two lines of evidence in support
      of the hypothesis that Amfor affects division of labor by modulating phototaxis.
      We first show that a subset of worker bees involved in the removal of corpses
      from the hive had forager-like brain levels of Amfor brain expression despite
      being middle aged; age-matched food-handlers, who do not leave the hive to
      perform their job, had low levels of Amfor expression. This finding suggests that
      occupations that involve working outside the hive are associated with high levels
      of Amfor in brain. Secondly, foragers were much more positively phototactic than
      hive bees in a laboratory assay, and cGMP treatment caused a precocious onset of
      positive phototaxis. The cGMP effect was not due to a general increase in
      behavioral activity; cGMP treatment had no effect on locomotor activity under
      either constant darkness or a light:dark regime. The cGMP effect also was not due
      to changes in circadian rhythmicity; cGMP treatment had no effect on age at onset
      of locomotor circadian rhythmicity or the period of rhythmicity. The effects of
      Amfor on phototaxis are not related to peripheral processing; electroretinogram
      analysis revealed no effect of cGMP treatment on photoreceptor activity and no
      differences between untreated hive bees and foragers. The cAMP/PKA pathway does
      not appear to be playing a similar role to cGMP/PKG in the honey bee; cAMP
      treatment did not affect phototaxis and gene expression analysis revealed task
      related differences only for the gene encoding the regulatory subunit, but not
      the catalytic subunit, of PKA. Our findings implicate one neural process
      associated with honey bee division of labor that can be affected by naturally
      occurring changes in the expression of AMFOR:

PMID- 12796465
TI  - Freezing and anoxia stresses induce expression of metallothionein in the foot
      muscle and hepatopancreas of the marine gastropod Littorina littorea.
AB  - Differential screening of cDNA libraries constructed from the foot muscle of
      marine snails Littorina littorea revealed several cDNAs that are upregulated
      during anoxia or freezing exposures, environmental stresses that are naturally
      endured by this species. One full-length clone of 1196 nucleotides (GenBank
      accession number AY034179) hybridized with a 1200-nucleotide band on northern
      blots and encoded a 100-amino-acid protein that was identified as belonging to
      the metallothionein (MT) family. L. littorea MT shared 45% and 56% identity with
      the copper- and cadmium-binding MT isoforms, respectively, from another
      gastropod, Helix pomatia and 43-47% identity with marine bivalve MTs. The L.
      littorea sequence included the mollusc-specific C-terminal motif Cys-X-Cys-X(3)
      Cys-Thr-Gly-X(3)-Cys-X-Cys-X(3)-Cys-X-Cys-Lys that identifies it as a family 2
      (mollusc) MT. Northern blot analysis showed that L. littorea MT was upregulated
      in both foot muscle and hepatopancreas in response to both freezing and anoxia
      stresses; within 1 h of the beginning of the stress transcript levels rose 2.5-
      to sixfold of control levels, reaching maximal levels at 12 or 24 h. After 24 h
      recovery from either stress, transcript levels were reduced again in three cases
      but remained elevated in hepatopancreas from anoxia-treated snails. Upregulation
      of MT during environmental stress could serve one or more possible roles,
      including a function in antioxidant defense.

PMID- 12796466
TI  - Visualization of the genesis and fate of isotype-switched B cells during a
      primary immune response.
AB  - The life history of isotype-switched B cells is unclear, in part, because of an
      inability to detect rare antigen-specific B cells at early times during the
      immune response. To address this issue, a small population of B cells carrying
      targeted antibody transgenes capable of class switching was monitored in
      immunized mice. After contacting helper T cells, the first switched B cells
      appeared in follicles rather than in the red pulp, as was expected. Later, some
      of the switched B cells transiently occupied the red pulp and marginal zone,
      whereas others persisted in germinal centers (GCs). Antigen-experienced IgM B
      cells were rarely found in GCs, indicating that these cells switched rapidly
      after entering GCs or did not persist in this environment.

PMID- 12796467
TI  - Unmutated immunoglobulin M can protect mice from death by influenza virus
      infection.
AB  - To elucidate the role of class switch recombination (CSR) and somatic
      hypermutation (SHM) in virus infection, we have investigated the influence of the
      primary and secondary infections of influenza virus on mice deficient of
      activation-induced cytidine deaminase (AID), which is absolutely required for CSR
      and SHM. In the primary infection, AID deficiency caused no significant
      difference in mortality but did cause difference in morbidity. In the secondary
      infection with a lethal dose of influenza virus, both AID-/- and AID+/- mice
      survived completely. However, AID-/- mice could not completely block replication
      of the virus and their body weights decreased severely whereas AID+/- mice showed
      almost complete prevention from the reinfection. Depletion of CD8+ T cells by
      administration of an anti-CD8 monoclonal antibody caused slightly severer body
      weight loss but did not alter the survival rate of AID-/- mice in secondary
      infection. These results indicate that unmutated immunoglobulin (Ig)M alone is
      capable of protecting mice from death upon primary and secondary infections.
      Because the titers of virus-neutralizing antibodies were comparable between AID-/
      and AID+/- mice at the time of the secondary infection, a defect of AID-/- mice
      in protection of morbidity might be due to the absence of either other Ig classes
      such as IgG, high affinity antibodies with SHM, or both.

PMID- 12796468
TI  - CD36 mediates the innate host response to beta-amyloid.
AB  - Accumulation of inflammatory microglia in Alzheimer's senile plaques is a
      hallmark of the innate response to beta-amyloid fibrils and can initiate and
      propagate neurodegeneration characteristic of Alzheimer's disease (AD). The
      molecular mechanism whereby fibrillar beta-amyloid activates the inflammatory
      response has not been elucidated. CD36, a class B scavenger receptor, is
      expressed on microglia in normal and AD brains and binds to beta-amyloid fibrils
      in vitro. We report here that microglia and macrophages, isolated from CD36 null
      mice, had marked reductions in fibrillar beta-amyloid-induced secretion of
      cytokines, chemokines, and reactive oxygen species. Intraperitoneal and
      stereotaxic intracerebral injection of fibrillar beta-amyloid in CD36 null mice
      induced significantly less macrophage and microglial recruitment into the
      peritoneum and brain, respectively, than in wild-type mice. Our data reveal that
      CD36, a major pattern recognition receptor, mediates microglial and macrophage
      response to beta-amyloid, and imply that CD36 plays a key role in the
      proinflammatory events associated with AD.

PMID- 12796469
TI  - A reversible defect in natural killer T cell function characterizes the
      progression of premalignant to malignant multiple myeloma.
AB  - We studied the function of antitumor T and natural killer T (NKT) cells from the
      blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive
      myeloma, or progressive multiple myeloma. We show that antitumor killer T cells
      can be detected in patients with both progressive or nonprogressive myeloma. V
      alpha 24+V beta 11+ invariant NKT cells are detectable in the blood and tumor bed
      of all cohorts. However, freshly isolated NKT cells from both the blood and tumor
      bed of patients with progressive disease, but not nonprogressive myeloma or
      premalignant gammopathy, have a marked deficiency of ligand-dependent interferon
      gamma production. This functional defect can be overcome in vitro using dendritic
      cells pulsed with the NKT ligand, alpha-galactosylceramide (alpha-GalCer). Fresh
      myeloma cells express CD1d, and can be efficiently killed by autologous NKT
      cells. We hypothesize that presentation of tumor derived glycolipids by myeloma
      cells leads to NKT dysfunction in vivo. These data demonstrate that clinical
      progression in patients with monoclonal gammopathies is associated with an
      acquired but potentially reversible defect in NKT cell function and support the
      possibility that these innate lymphocytes play a role in controlling the
      malignant growth of this incurable B cell tumor in patients.

PMID- 12796470
TI  - Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like
      receptor 4 gene show no deficit in lipopolysaccharide signalling.
AB  - Toll-like receptor 4 (TLR4)-mediated recognition of lipopolysaccharide (LPS) is
      required for efficient recognition of Gram-negative bacterial infections. Two
      commonly occurring mutations in the human TLR4 gene (Asp299Gly and Thr399Ile)
      have recently been shown to be associated with blunted physiological responses to
      inhaled LPS, and with increased risk of Gram-negative bacteraemia in sepsis
      patients and reduced risk of atherosclerosis in an Italian population. Here we
      show that monocytes from individuals heterozygous for both mutations in the TLR4
      gene exhibit no deficit in recognition of LPS of Escherichia coli, Neisseria
      meningitidis, Bacteroides fragilis, Yersinia pestis, Chlamydia trachomatis,
      Porphyromonas gingivalis, or Pseudomonas aeruginosa. We propose that the
      relatively high frequency of these mutations in the Caucasian population may
      reflect modified responses of carriers to alternative TLR4 agonists.

PMID- 12796471
TI  - Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.
AB  - Experiments in nonobese diabetic (NOD) mice that lacked expression of glutamic
      acid decarboxylase (GAD) in beta cells have suggested that GAD represents an
      autoantigen essential for initiating and maintaining the diabetogenic immune
      response. Several attempts of inducing GAD-specific recessive tolerance to
      support this hypothesis have failed. Here we report on successful tolerance
      induction by expressing a modified form of GAD under control of the invariant
      chain promoter resulting in efficient epitope display. In spite of specific
      tolerance insulitis and diabetes occurred with normal kinetics indicating that
      GAD is not an essential autoantigen in the pathogenesis of diabetes.

PMID- 12796473
TI  - The liberation of CD44.
AB  - CD44 was once thought to simply be a transmembrane adhesion molecule that also
      played a role in the metabolism of its principal ligand hyaluronan.
      Investigations of CD44 over the past approximately 20 yr have established
      additional functions for CD44, including its capacity to mediate inflammatory
      cell function and tumor growth and metastasis. It has also become evident that
      intricate posttranslational modifications of CD44 regulate the affinity of the
      receptor for its ligands. In this review, we focus on emerging evidence that
      functional fragments of the cytoplasmic and ectodomain of CD44 can be liberated
      by enzymatic modification of cell surfaces as well as of cell-associated matrix.
      Based on the evidence discussed, we propose that CD44 exists in three phases, as
      a transmembrane receptor, as an integral component of the matrix, and as a
      soluble protein found in body fluids, each with biologically significant
      functions of which some are shared and some distinct. Thus, CD44 represents a
      model for understanding posttranslational processing and its emerging role as a
      general mechanism for regulating cell behavior.

PMID- 12796474
TI  - Regulation of leading edge microtubule and actin dynamics downstream of Rac1.
AB  - Actin in migrating cells is regulated by Rho GTPases. However, Rho proteins might
      also affect microtubules (MTs). Here, we used time-lapse microscopy of PtK1 cells
      to examine MT regulation downstream of Rac1. In these cells, "pioneer" MTs
      growing into leading-edge protrusions exhibited a decreased catastrophe frequency
      and an increased time in growth as compared with MTs further from the leading
      edge. Constitutively active Rac1(Q61L) promoted pioneer behavior in most MTs,
      whereas dominant-negative Rac1(T17N) eliminated pioneer MTs, indicating that Rac1
      is a regulator of MT dynamics in vivo. Rac1(Q61L) also enhanced MT turnover
      through stimulation of MT retrograde flow and breakage. Inhibition of p21
      activated kinases (Paks), downstream effectors of Rac1, inhibited Rac1(Q61L)
      induced MT growth and retrograde flow. In addition, Rac1(Q61L) promoted
      lamellipodial actin polymerization and Pak-dependent retrograde flow. Together,
      these results indicate coordinated regulation of the two cytoskeletal systems in
      the leading edge of migrating cells.

PMID- 12796475
TI  - Requirement of transcription factor NFAT in developing atrial myocardium.
AB  - Nuclear factor of activated T cell (NFAT) is a ubiquitous regulator involved in
      multiple biological processes. Here, we demonstrate that NFAT is temporally
      required in the developing atrial myocardium between embryonic day 14 and P0
      (birth). Inhibition of NFAT activity by conditional expression of dominant
      negative NFAT causes thinning of the atrial myocardium. The thin myocardium
      exhibits severe sarcomere disorganization and reduced expression of cardiac
      troponin-I (cTnI) and cardiac troponin-T (cTnT). Promoter analysis indicates that
      NFAT binds to and regulates transcription of the cTnI and the cTnT genes. Thus,
      regulation of cytoskeletal protein gene expression by NFAT may be important for
      the structural architecture of the developing atrial myocardium.

PMID- 12796476
TI  - The fission yeast cytokinesis formin Cdc12p is a barbed end actin filament
      capping protein gated by profilin.
AB  - Cytokinesis in most eukaryotes requires the assembly and contraction of a ring of
      actin filaments and myosin II. The fission yeast Schizosaccharomyces pombe
      requires the formin Cdc12p and profilin (Cdc3p) early in the assembly of the
      contractile ring. The proline-rich formin homology (FH) 1 domain binds profilin,
      and the FH2 domain binds actin. Expression of a construct consisting of the Cdc12
      FH1 and FH2 domains complements a conditional mutant of Cdc12 at the restrictive
      temperature, but arrests cells at the permissive temperature. Cells
      overexpressing Cdc12(FH1FH2)p stop growing with excessive actin cables but no
      contractile rings. Like capping protein, purified Cdc12(FH1FH2)p caps the barbed
      end of actin filaments, preventing subunit addition and dissociation, inhibits
      end to end annealing of filaments, and nucleates filaments that grow exclusively
      from their pointed ends. The maximum yield is one filament pointed end per six
      formin polypeptides. Profilins that bind both actin and poly-l-proline inhibit
      nucleation by Cdc12(FH1FH2)p, but polymerization of monomeric actin is faster,
      because the filaments grow from their barbed ends at the same rate as uncapped
      filaments. On the other hand, Cdc12(FH1FH2)p blocks annealing even in the
      presence of profilin. Thus, formins are profilin-gated barbed end capping
      proteins with the ability to initiate actin filaments from actin monomers bound
      to profilin. These properties explain why contractile ring assembly requires both
      formin and profilin and why viability depends on the ability of profilin to bind
      both actin and poly-l-proline.

PMID- 12796477
TI  - BMPs signal alternately through a SMAD or FRAP-STAT pathway to regulate fate
      choice in CNS stem cells.
AB  - The ability of stem cells to generate distinct fates is critical for the
      generation of cellular diversity during development. Central nervous system (CNS)
      stem cells respond to bone morphogenetic protein (BMP) 4 by differentiating into
      a wide variety of dorsal CNS and neural crest cell types. We show that distinct
      mechanisms are responsible for the generation of two of these cell types, smooth
      muscle and glia. Smooth muscle differentiation requires BMP-mediated Smad1/5/8
      activation and predominates where local cell density is low. In contrast, glial
      differentiation predominates at high local densities in response to BMP4 and is
      specifically blocked by a dominant-negative mutant Stat3. Upon BMP4 treatment,
      the serine-threonine kinase FKBP12/rapamycin-associated protein (FRAP), mammalian
      target of rapamycin (mTOR), associates with Stat3 and facilitates STAT
      activation. Inhibition of FRAP prevents STAT activation and glial
      differentiation. Thus, glial differentiation by BMP4 occurs by a novel pathway
      mediated by FRAP and STAT proteins. These results suggest that a single ligand
      can regulate cell fate by activating distinct cytoplasmic signals.

PMID- 12796478
TI  - The COOH-terminal domain of agrin signals via a synaptic receptor in central
      nervous system neurons.
AB  - Agrin is a motor neuron-derived factor that directs formation of the postsynaptic
      apparatus of the neuromuscular junction. Agrin is also expressed in the brain,
      raising the possibility that it might serve a related function at neuron-neuron
      synapses. Previously, we identified an agrin signaling pathway in central nervous
      system (CNS) neurons, establishing the existence of a neural receptor that
      mediates responses to agrin. As a step toward identifying this agrin receptor, we
      have characterized the minimal domains in agrin that bind and activate it.
      Structures required for agrin signaling in CNS neurons are contained within a 20
      kD COOH-terminal fragment of the protein. Agrin signaling is independent of
      alternative splicing at the z site, but requires sequences that flank it because
      their deletion results in a 15-kD fragment that acts as an agrin antagonist.
      Thus, distinct regions within agrin are responsible for receptor binding and
      activation. Using the minimal agrin fragments as affinity probes, we also studied
      the expression of the agrin receptor on CNS neurons. Our results show that both
      agrin and its receptor are concentrated at neuron-neuron synapses. These data
      support the hypothesis that agrin plays a role in formation and/or function of
      CNS synapses.

PMID- 12796479
TI  - Reactive oxygen species as essential mediators of cell adhesion: the oxidative
      inhibition of a FAK tyrosine phosphatase is required for cell adhesion.
AB  - Signal transduction by reactive oxygen species (ROS; "redox signaling") has
      recently come into focus in cellular biology studies. The signaling properties of
      ROS are largely due to the reversible oxidation of redox-sensitive target
      proteins, and especially of protein tyrosine phosphatases, whose activity is
      dependent on the redox state of a low pKa active site cysteine. A variety of
      mitogenic signals, including those released by receptor tyrosine kinase (RTKs)
      ligands and oncogenic H-Ras, involve as a critical downstream event the
      intracellular generation of ROS. Signaling by integrins is also essential for the
      growth of most cell types and is constantly integrated with growth factor
      signaling. We provide here evidence that intracellular ROS are generated after
      integrin engagement and that these oxidant intermediates are necessary for
      integrin signaling during fibroblast adhesion and spreading. Moreover, we propose
      a synergistic action of integrins and RTKs for redox signaling. Integrin-induced
      ROS are required to oxidize/inhibit the low molecular weight phosphotyrosine
      phosphatase, thereby preventing the enzyme from dephosphorylating and
      inactivating FAK. Accordingly, FAK phosphorylation and other downstream events,
      including MAPK phosphorylation, Src phosphorylation, focal adhesion formation,
      and cell spreading, are all significantly attenuated by inhibition of redox
      signaling. Hence, we have outlined a redox circuitry whereby, upon cell adhesion,
      oxidative inhibition of a protein tyrosine phosphatase promotes the
      phosphorylation/activation and the downstream signaling of FAK and, as a final
      event, cell adhesion and spreading onto fibronectin.

PMID- 12796480
TI  - Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear
      phagocytes.
AB  - Tetraspanins CD9 and CD81 facilitate the fusion between gametes, myoblasts, or
      virus-infected cells. Here, we investigated the role of these tetraspanins in the
      fusion of mononuclear phagocytes. Expression of CD9 and CD81 and their complex
      formation with integrins were up-regulated when blood monocytes were cultured
      under normal conditions. Under fusogenic conditions in the presence of Con A, CD9
      and CD81 up-regulation was inhibited, and their complex formation with integrins
      was down-regulated. Anti-CD9 and -CD81 antibodies, which were previously shown to
      inhibit the fusion of gametes, myoblasts, and virus-infected cells, unexpectedly
      promoted the fusion of monocytes and alveolar macrophages. However, these effects
      were not due to altered cell adhesion, aggregation, or cytokine production. When
      stimulated in vitro or in vivo, alveolar macrophages and bone marrow cells of CD9
      and CD81-null mice formed larger numbers of multinucleated cells than those of
      wild-type mice. Finally, CD9/CD81 double-null mice spontaneously developed
      multinucleated giant cells in the lung and showed enhanced osteoclastogenesis in
      the bone. These results suggest that CD9 and CD81 coordinately prevent the fusion
      of mononuclear phagocytes.

PMID- 12796482
TI  - The crystal structure of DJ-1, a protein related to male fertility and
      Parkinson's disease.
AB  - DJ-1 is a multifunctional protein that plays essential roles in tissues with
      higher order biological functions such as the testis and brain. DJ-1 is related
      to male fertility, and its level in sperm decreases in response to exposure to
      sperm toxicants. DJ-1 has also been identified as a hydroperoxide-responsive
      protein. Recently, a mutation of DJ-1 was found to be responsible for familial
      Parkinson's disease. Here, we present the crystal structure of DJ-1 refined to
      1.95-A resolution. DJ-1 forms a dimer in the crystal, and the monomer takes a
      flavodoxin-like Rossmann-fold. DJ-1 is structurally most similar to the monomer
      subunit of protease I, the intracellular cysteine protease from Pyrococcus
      horikoshii, and belongs to the Class I glutamine amidotransferase-like
      superfamily. However, DJ-1 contains an additional alpha-helix at the C-terminal
      region, which blocks the putative catalytic site of DJ-1 and appears to regulate
      the enzymatic activity. DJ-1 may induce conformational changes to acquire
      catalytic activity in response to oxidative stress.

PMID- 12796481
TI  - A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth
      factor-regulated channel.
AB  - Disruption of the dystrophin-glycoprotein complex caused by genetic defects of
      dystrophin or sarcoglycans results in muscular dystrophy and/or cardiomyopathy in
      humans and animal models. However, the key early molecular events leading to
      myocyte degeneration remain elusive. Here, we observed that the growth factor
      regulated channel (GRC), which belongs to the transient receptor potential
      channel family, is elevated in the sarcolemma of skeletal and/or cardiac muscle
      in dystrophic human patients and animal models deficient in dystrophin or delta
      sarcoglycan. However, total cell GRC does not differ markedly between normal and
      dystrophic muscles. Analysis of the properties of myotubes prepared from delta
      sarcoglycan-deficient BIO14.6 hamsters revealed that GRC is activated in response
      to myocyte stretch and is responsible for enhanced Ca2+ influx and resultant cell
      damage as measured by creatine phosphokinase efflux. We found that cell stretch
      increases GRC translocation to the sarcolemma, which requires entry of external
      Ca2+. Consistent with these findings, cardiac-specific expression of GRC in a
      transgenic mouse model produced cardiomyopathy due to Ca2+ overloading, with
      disease expression roughly parallel to sarcolemmal GRC levels. The results
      suggest that GRC is a key player in the pathogenesis of myocyte degeneration
      caused by dystrophin-glycoprotein complex disruption.

PMID- 12796483
TI  - Comparison of soluble decoy IgG fusion proteins of BAFF-R and BCMA as antagonists
      for BAFF.
AB  - BAFF is considered a therapeutic target because dysregulated production of BAFF
      can induce systemic lupus erythematosus-like phenotype in mice, and elevated
      levels of BAFF are associated with disease severity in systemic lupus
      erythematosus and rheumatoid arthritis patients. Fc fusion decoy receptors, BCMA
      Fc and BAFF-R-Fc, are therapeutic candidates for blocking BAFF. While studying
      their interactions with BAFF, we found that BAFF-R-Fc is more effective than BCMA
      Fc for blocking BAFF binding to its receptors. We also found that a trimeric BAFF
      can bind more than one BAFF-R-Fc but only one BCMA-Fc. Moreover, we show that, in
      contrast to monovalent BAFF-R-Fc, monovalent BCMA does not form stable complexes
      with BAFF. Differences in their interaction with BAFF predict BAFF-R-Fc would be
      a better inhibitor. Indeed, we show BAFF-R-Fc is 10-fold more efficacious than
      BCMA-Fc for blocking BAFF-induced B cell proliferation in vitro and for blocking
      BAFF-mediated survival of mouse splenic B lymphocytes in vivo.

PMID- 12796484
TI  - The trafficking of alpha 1-antitrypsin, a post-Golgi secretory pathway marker, in
      INS-1 pancreatic beta cells.
AB  - A sulfated alpha1-antitrypsin (AAT), thought to be a default secretory pathway
      marker, is not stored in secretory granules when expressed in neuroendocrine PC12
      cells. In search of a constitutive secretory pathway marker for pancreatic beta
      cells, we produced INS-1 cells stably expressing wild-type AAT. Because newly
      synthesized AAT arrives very rapidly in the Golgi complex, kinetics alone cannot
      resolve AAT release via distinct secretory pathways, although most AAT is
      secreted within a few hours and virtually none is stored in mature granules.
      Nevertheless, from pulse-chase analyses, a major fraction of newly synthesized
      AAT transiently exhibits secretogogue-stimulated exocytosis and localizes within
      immature secretory granules (ISGs). This trafficking occurs without detectable
      AAT polymerization or binding to lipid rafts. Remarkably, in a manner not
      requiring its glycans, all of the newly synthesized AAT is then removed from
      granules during their maturation, leading mostly to constitutive-like AAT
      secretion, whereas a smaller fraction (approximately 10%) goes on to lysosomes.
      Secretogogue-stimulated ISG exocytosis reroutes newly synthesized AAT directly
      into the medium and prevents its arrival in lysosomes. These data are most
      consistent with the idea that soluble AAT abundantly enters ISGs and then is
      efficiently relocated to the endosomal system, from which many molecules undergo
      constitutive-like secretion while a smaller fraction advances to lysosomes.

PMID- 12796485
TI  - Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells
      by repressing p21WAF1/Cip1 transcription and cyclin D1-Cdk4-p21WAF1/Cip1 complex
      formation.
AB  - Atherosclerosis and restenosis are common vascular disorders that involve excess
      proliferation of smooth muscle cells (SMCs) in the artery wall. In this study we
      demonstrate the anti-mitogenic, pro-apoptotic role of the zinc finger
      transcription factor Sp1 in vascular SMCs and define the underlying molecular
      mechanism via its capacity to repress the expression of the cyclin-dependent
      kinase inhibitor p21WAF1/Cip1 at the level of transcription, mRNA, and protein.
      SMC proliferation inducible by a dominant-negative mutant form of Sp1 was
      abrogated by antisense strategies targeting p21WAF1/Cip1. Conversely, antisense
      p21WAF1/Cip1 induced apoptosis in SMCs overexpressing dominant-negative-Sp1.
      p21WAF1/Cip1 overexpression alone stimulated proliferation and inhibited
      apoptosis. Sp1 down-regulated p21WAF1/Cip1 expression in SMCs. Sp1 blocked
      assembly of cyclin D1-Cdk4-p21WAF1/Cip1 complex formation whose integrity is
      critical for G1->S transition. Moreover, Rb phosphorylation, which lies
      immediately downstream of the cyclin D1-Cdk4-p21WAF1/Cip1 complex, was blocked
      either by Sp1 overexpression or antisense p21WAF1/Cip1. These findings, using
      complementary approaches, demonstrate the inverse relationship between Sp1 and
      p21WAF1/Cip1 in SMCs and the capacity of Sp1 to regulate SMC proliferation and
      apoptosis via its repression of p21WAF1/Cip1.

PMID- 12796486
TI  - Crystal structure of Pyrococcus furiosus phosphoglucose isomerase. Implications
      for substrate binding and catalysis.
AB  - Phosphoglucose isomerase (PGI) catalyzes the reversible isomerization between d
      fructose 6-phosphate and d-glucose 6-phosphate as part of the glycolytic pathway.
      PGI from the Archaea Pyrococcus furiosus (Pfu) was crystallized, and its
      structure was determined by x-ray diffraction to a 2-A resolution. Structural
      comparison of this archaeal PGI with the previously solved structures of
      bacterial and eukaryotic PGIs reveals a completely different structure. Each
      subunit of the homodimeric Pfu PGI consists of a cupin domain, for which the
      overall structure is similar to other cupin domain-containing proteins, and
      includes a conserved transition metal-binding site. Biochemical data on the
      recombinant enzyme suggests that Fe2+ is bound to Pfu PGI. However, as catalytic
      activity is not strongly influenced either by the replacement of Fe2+ by a range
      of transition metals or by the presence or absence of the bound metal ion, we
      suggest that the metal may not be directly involved in catalysis but rather may
      be implicated in substrate recognition.

PMID- 12796487
TI  - Molecular structure of galactokinase.
AB  - Galactokinase plays a key role in normal galactose metabolism by catalyzing the
      ATP-dependent phosphorylation of alpha-D-galactose to galactose 1-phosphate. In
      humans, mutations in the galactokinase gene can lead to the diseased state
      referred to as Type II galactosemia. Here we describe the three-dimensional
      structure of galactokinase from Lactococcus lactis determined to 2.1-A
      resolution. As expected from amino acid sequence alignments, galactokinase adopts
      a similar topology to that observed for members of the GHMP superfamily. The N
      terminal domain is characterized by a five-stranded mixed beta-sheet while the C
      terminal motif is dominated by two distinct four-stranded anti-parallel beta
      sheets. The structure was solved in the presence of alpha-D-galactose and
      inorganic phosphate. These ligands are wedged between the N- and C-terminal
      domains. Amino acid side chains responsible for anchoring the sugar ligand to the
      protein include Arg36, Glu42, Asp45, Asp183, and Tyr233. Both Arg36 and Asp183
      are strictly conserved in the amino acid sequences available in the literature
      thus far for galactokinases. Interestingly, the carboxylate side chain of Asp183
      is positioned within 3.5 A of the C-1 hydroxyl group of galactose, whereas the
      guanidinium group of Arg36 is situated between both the C-1 hydroxyl group and
      the inorganic phosphate. Most likely these residues play key roles in catalysis.
      The structure of galactokinase described here serves as a model for understanding
      the functional consequences of point mutations known to result in Type II
      galactosemia in humans.

PMID- 12796488
TI  - 2-Methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 potently stimulates gene
      specific DNA binding of the vitamin D receptor in osteoblasts.
AB  - 2-Methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 (2MD) is a highly potent analog
      of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) whose actions are mediated through the
      vitamin D receptor (VDR). In this report, we have replicated this increased
      potency of 2MD in vitro using osteoblastic cells and explored its underlying
      molecular mechanism. 2MD stimulates the expression of several vitamin D-sensitive
      genes including 25-hydroxyvitamin D3-24 hydroxylase (Cyp24), osteopontin and
      receptor activator of NF kappa B ligand and suppresses osteoprotegerin at
      concentrations two logs lower than that for 1,25(OH)2D3. 2MD is also more potent
      in stimulating transfected chimeric reporter genes under either Cyp24 or the
      osteocalcin promoter control. Enhanced potency is retained regardless of medium
      serum content. Interestingly, the uptake of both 1,25(OH)2D3 and 2MD into cells
      is similar, as is their rapid association with the VDR. This indicates that
      comparable levels of occupied VDR do not elicit equivalent levels of
      transactivation. Using chromatin immunoprecipitation (ChIP), however, we observed
      a strong correlation between DNA-bound receptor and the level of induced
      transcription suggesting a 2MD-induced increase in affinity of the VDR for DNA.
      Additional studies using a mammalian two-hybrid system and ChIP indicate that 2MD
      is also more potent in promoting interaction with RXR and the coactivators SRC-1
      and DRIP205. Finally, protease digestion studies revealed a unique VDR
      conformation in the presence of 2MD. These studies suggest that the molecular
      mechanism of 2MD potency is due to its ability to promote enhanced levels of
      specific DNA binding by the VDR and could suggest possible explanations for the
      tissue- and gene-selective actions of 2MD.

PMID- 12796489
TI  - Cloning and characterization of N4WBP5A, an inducible, cyclosporine-sensitive,
      Nedd4-binding protein in human T lymphocytes.
AB  - We have cloned and characterized a human cDNA, designated N4WBP5A, that belongs
      to the family of Nedd4-binding proteins. We originally identified N4WBP5A as an
      unknown expressed sequence tag (AA770150) represented in a cDNA microarray
      analysis that was up-regulated upon activation of T cells and inhibited by cell
      treatment with the calcineurin phosphatase inhibitors, cyclosporine (CsA) and
      tacrolimus (FK506). The predicted N4WBP5A amino acid sequence of 242 amino acid
      residues reveals an open reading frame of 729 nucleotides with a corresponding
      molecular mass of 27.1 kDa. Detection of N4WBP5A mRNA by reverse transcription
      PCR was consistent with the induction of N4WBP5A following mitogenic stimulation
      of T lymphocytes and inhibition by CsA. Immunoblot analysis revealed endogenous
      N4WBP5A protein to be up-regulated following T cell activation and inhibited by
      CsA. This regulation of N4WBP5A mRNA expression differed from that of its
      homologue (51% identical; 65% similar) N4WBP5. Like N4WBP5, however, expression
      of epitope-tagged N4WBP5A indicated that the protein is localized predominantly
      to the Golgi network. Here we show by co-precipitation experiments that N4WBP5A
      interacts with the WW domains of Nedd4, an E3 ubiquitin ligase. Taken together,
      our data suggest that N4WBP5A may play a regulatory role in modulating Nedd4
      activity at the level of the Golgi apparatus in T lymphocytes.

PMID- 12796490
TI  - Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse
      Schwann cells require the stimulation of P2X7 receptors.
AB  - The P2X7 receptor, mainly expressed by immune cells, is a ionotropic receptor
      activated by high concentration of extracellular ATP. It is involved in several
      processes relevant to immunomodulation and inflammation. Among these processes,
      the production of extracellular interleukin-1beta (IL-1beta), a pro-inflammatory
      cytokine, plays a major role in the activation of the cytokine network. We have
      investigated the role of P2X7 receptor and of an associated calcium-activated
      potassium conductance (BK channels) in IL-1beta maturation and releasing
      processes by Schwann cells. Lipopolysaccharide-primed Schwann cells synthesized
      large amounts of pro-IL-1beta but did not release detectable amounts of pro or
      mature IL-1beta. ATP on its own had no effect on the synthesis of pro-IL-1beta,
      but a co-treatment with lipopolysaccharide and ATP led to the maturation and the
      release of IL-1beta by Schwann cells. Both mechanisms were blocked by oxidized
      ATP. IL-1beta-converting enzyme (ICE), the caspase responsible for the maturation
      of pro-IL-1beta in IL-1beta, was activated by P2X7 receptor stimulation. The
      specific inhibition of ICE by the caspase inhibitor Ac-Tyr-Val-Ala-Asp-aldehyde
      blocked the maturation of IL-1beta. In searching for a link between the P2X7
      receptor and the activation of ICE, we found that enhancing potassium efflux from
      Schwann cells upregulated the production of IL-1beta, while strongly reducing
      potassium efflux led to opposite effects. Blocking BK channels actually modulated
      IL-1beta release. Taken together, these results show that P2X7 receptor
      stimulation and associated BK channels, through the activation of ICE, leads to
      the maturation and the release of IL-1beta by immune-challenged Schwann cells.

PMID- 12796491
TI  - Transgenic mice expressing lipoprotein lipase in adipose tissue. Absence of the
      proximal 3'-untranslated region causes translational upregulation.
AB  - Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism.
      Defects in LPL can lead to hypertriglyceridemia and the subsequent development of
      atherosclerosis. The mechanisms of regulation of this enzyme are complex and may
      occur at multiple levels of gene expression. Because the 3'-untranslated region
      (UTR) is involved in LPL translational regulation, transgenic mice were generated
      with adipose tissue expression of an LPL construct either with or without the
      proximal 3'-UTR and driven by the aP2 promoter. Both transgenic mouse colonies
      were viable and expressed the transgene, resulting in a 2-fold increase in LPL
      activity in white adipose tissue. Neither mouse colony exhibited any obvious
      phenotype in terms of body weight, plasma lipids, glucose, and non-esterified
      fatty acid levels. In the mice expressing hLPL with an intact 3'-UTR, hLPL mRNA
      expression approximately paralleled hLPL activity. However in the mice without
      the proximal 3'-UTR, hLPL mRNA was low in the setting of large amounts of hLPL
      protein and LPL activity. In previous studies, the 3'-UTR of LPL was critical for
      the inhibitory effects of constitutively expressed hormones, such as thyroid
      hormone and catecholamines. Therefore, these data suggest that the absence of the
      3'-UTR results in a translationally unrepressed LPL, resulting in a moderate
      overexpression of adipose LPL activity.

PMID- 12796492
TI  - RSK2 activity is regulated by its interaction with PEA-15.
AB  - The ERK MAP (mitogen-activated protein) kinase cascade modulates many cellular
      processes including transcription, adhesion, growth, survival, and proliferation.
      One target substrate of ERK involved in regulating transcription is the p90
      ribosomal S6 kinase (RSK) isozyme, RSK2. Here we demonstrate that a small death
      effector domain-containing protein called PEA-15 binds RSK2. RSK2 and PEA-15
      (phosphoprotein enriched in astrocytes, 15 kDa) co-precipitated from cells and
      were colocalized in the cytoplasm. Furthermore, purified PEA-15 bound in vitro
      translated RSK2, suggesting that these proteins interact directly. PEA-15 does
      not bind to RSK1 and therefore exhibits some binding specificity. RSK2 binds the
      COOH terminus of PEA-15 and does not interact with its NH2-terminal death
      effector domain. We show that this interaction has functional consequences
      including the inhibition of RSK2-dependent CREB transcription. PEA-15 expression
      also blocks histone H3 phosphorylation, an RSK2-dependent event that may
      contribute to effects on gene expression. These results can be attributed to two
      effects of PEA-15 on RSK2. First, PEA-15 blocks nuclear accumulation of RSK2
      after epidermal growth factor stimulation. Second, PEA-15 inhibits RSK2 kinase
      activity by 50%. A mutant of PEA-15 that binds RSK2 but is localized to the
      nucleus had no effect on RSK2-dependent transcription. Interestingly, this mutant
      also did not affect RSK2 kinase activity. This may indicate that cytoplasmic
      retention of RSK2 is also required for PEA-15 to impair kinase activity. PEA-15
      does not alter ERK phosphorylation of RSK2 and is not itself a substrate of RSK2.
      Hence the effects of PEA-15 on RSK2 represent a novel mechanism for the
      regulation of RSK2-mediated signaling.

PMID- 12796493
TI  - GroEL stability and function. Contribution of the ionic interactions at the inter
      ring contact sites.
AB  - The chaperonin GroEL consists of a double ring structure made of identical
      subunits that display different modes of allosteric communication. The protein
      folding cycle requires the simultaneous positive intra-ring and negative inter
      ring cooperativities of ATP binding. This ensures GroES binding to one ring and
      release of the ligands from the opposite one. To better characterize inter-ring
      allosterism, the thermal stability as well as the temperature dependence of the
      functional and conformational properties of wild type GroEL, a single ring mutant
      (SR1) and two single point mutants suppressing one interring salt bridge (E434K
      and E461K) were studied. The results indicate that ionic interactions at the two
      interring contact sites are essential to maintain the negative cooperativity for
      protein substrate binding and to set the protein thermostat at 39 degrees C.
      These electrostatic interactions contribute distinctly to the stability of the
      inter-ring interface and the overall protein stability, e.g. the E434K thermal
      inactivation curve is shifted to lower temperatures, and its unfolding
      temperature and activation energy are also lowered. An analysis of the ionic
      interactions at the inter-ring contact sites reveals that at the so called "left
      site" a network of electrostatic interactions involving three charged residues
      might be established, in contrast to what is found at the "right site" where only
      two oppositely charged residues interact. Our data suggest that electrostatic
      interactions stabilize protein-protein interfaces depending on both the number of
      ionic interactions and the number of residues engaged in each of these
      interactions. In the case of GroEL, this combination sets the thermostat of the
      protein so that the chaperonin distinguishes physiological from stress
      temperatures.

PMID- 12796494
TI  - LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase
      in human cells.
AB  - We have reported that human immunodeficiency virus type 1 (HIV-1) integrase (IN)
      forms a specific nuclear complex with human lens epithelium-derived growth
      factor/transcription co-activator p75 (LEDGF/p75) protein. We now studied the IN
      LEDGF/p75 interaction and nuclear import of IN in living cells using fusions of
      IN and LEDGF/p75 with enhanced green fluorescent protein and far-red fluorescent
      protein HcRed1. We show that both the N-terminal zinc binding domain and the
      central core domains of IN are involved in the interaction with LEDGF/p75. Both
      domains are essential for nuclear localization of IN as well as for the
      association of IN with condensed chromosomes during mitosis. However, upon
      overexpression of LEDGF/p75, the core domain fragment of IN was recruited to the
      nuclei and mitotic chromosomes with a distribution pattern characteristic of the
      full-length protein, indicating that it harbors the main determinant for
      interaction with LEDGF/p75. Although the C-terminal domain of IN was dispensable
      for nuclear/chromosomal localization, a fusion of the C-terminal IN fragment with
      enhanced green fluorescent protein was found exclusively in the nucleus, with a
      diffuse nuclear/nucleolar distribution, suggesting that the C-terminal domain may
      also play a role in the nuclear import of IN. In contrast to LEDGF/p75, its
      alternative splice variant, p52, did not interact with HIV-1 IN in vitro and in
      living cells. Finally, RNA interference-mediated knock-down of endogenous
      LEDGF/p75 expression abolished nuclear/chromosomal localization of IN. We
      conclude, therefore, that the interaction with LEDGF/p75 accounts for the
      karyophilic properties and chromosomal targeting of HIV-1 IN.

PMID- 12796495
TI  - Folding and stability of the extracellular domain of the human amyloid precursor
      protein.
AB  - The beta-amyloid peptide (A beta), the major component of the senile plaques
      found in the brains of Alzheimer's disease patients, is derived from proteolytic
      processing of a transmembrane glycoprotein known as the amyloid precursor protein
      (APP). Human APP exists in various isoforms, of which the major ones contain 695,
      751, and 770 amino acids. Proteolytic cleavage of APP by alpha- or beta
      secretases releases the extracellular soluble fragments sAPP alpha or sAPP beta,
      respectively. Despite the fact that sAPP alpha plays important roles in both
      physiological and pathological processes in the brain, very little is known about
      its structure and stability. We have recently presented a structural model of
      sAPP alpha 695 obtained from small-angle x-ray scattering measurements (Gralle,
      M., Botelho, M. M., Oliveira, C. L. P., Torriani, I., and Ferreira, S. T. (2002)
      Biophys. J. 83, 3513-3524). We now report studies on the folding and stabilities
      of sAPP alpha 695 and sAPP alpha 770. The combined use of intrinsic fluorescence,
      4-4'-Dianilino-1,1'binaphthyl-5,5'-disulfonic acid (bis-ANS) fluorescence,
      circular dichroism, differential ultraviolet absorption, and small-angle x-ray
      scattering measurements of the equilibrium unfolding of sAPP alpha 695 and sAPP
      alpha 770 by GdnHCl and urea revealed multistep folding pathways for both sAPP
      alpha isoforms. Such stepwise folding processes may be related to the
      identification of distinct structural domains in the three-dimensional model of
      sAPP alpha. Furthermore, the relatively low stability of the native state of sAPP
      alpha suggests that conformational plasticity may play a role in allowing APP to
      interact with a number of distinct physiological ligands.

PMID- 12796496
TI  - Biophysical and structural analysis of a novel heme B iron ligation in the
      flavocytochrome cellobiose dehydrogenase.
AB  - The fungal extracellular flavocytochrome cellobiose dehydrogenase (CDH)
      participates in lignocellulose degradation. The enzyme has a cytochrome domain
      connected to a flavin-binding domain by a peptide linker. The cytochrome domain
      contains a 6-coordinate low spin b-type heme with unusual iron ligands and
      coordination geometry. Wild type CDH is only the second example of a b-type heme
      with Met-His ligation, and it is the first example of a Met-His ligation of heme
      b where the ligands are arranged in a nearly perpendicular orientation. To
      investigate the ligation further, Met65 was replaced with a histidine to create a
      bis-histidyl ligated iron typical of b-type cytochromes. The variant is expressed
      as a stable 90-kDa protein that retains the flavin domain catalytic reactivity.
      However, the ability of the mutant to reduce external one-electron acceptors such
      as cytochrome c is impaired. Electrochemical measurements demonstrate a decrease
      in the redox midpoint potential of the heme by 210 mV. In contrast to the wild
      type enzyme, the ferric state of the protoheme displays a mixed low spin/high
      spin state at room temperature and low spin character at 90 K, as determined by
      resonance Raman spectroscopy. The wild type cytochrome does not bind CO, but the
      ferrous state of the variant forms a CO complex, although the association rate is
      very low. The crystal structure of the M65H cytochrome domain has been determined
      at 1.9 A resolution. The variant structure confirms a bis-histidyl ligation but
      reveals unusual features. As for the wild type enzyme, the ligands have a nearly
      perpendicular arrangement. Furthermore, the iron is bound by imidazole N delta 1
      and N epsilon 2 nitrogen atoms, rather than the typical N epsilon 2/N epsilon 2
      coordination encountered in bis-histidyl ligated heme proteins. To our knowledge,
      this is the first example of a bis-histidyl N delta 1/N epsilon 2-coordinated
      protoporphyrin IX iron.

PMID- 12796497
TI  - Human group V phospholipase A2 induces group IVA phospholipase A2-independent
      cysteinyl leukotriene synthesis in human eosinophils.
AB  - We previously reported that exogenously added human group V phospholipase A2
      (hVPLA2) could elicit leukotriene B4 biosynthesis in human neutrophils through
      the activation of group IVA phospholipase A2 (cPLA2) (Kim, Y. J., Kim, K. P.,
      Han, S. K., Munoz, N. M., Zhu, X., Sano, H., Leff, A. R., and Cho, W. (2002) J.
      Biol. Chem. 277, 36479-36488). In this study, we determined the functional
      significance and mechanism of the exogenous hVPLA2-induced arachidonic acid (AA)
      release and leukotriene C4 (LTC4) synthesis in isolated human peripheral blood
      eosinophils. As low a concentration as 10 nm exogenous hVPLA2 was able to elicit
      the significant release of AA and LTC4 from unstimulated eosinophils, which
      depended on its ability to act on phosphatidylcholine membranes. hVPLA2 also
      augmented the release of AA and LTC4 from eosinophils activated with formyl-Met
      Leu-Phe + cytochalasin B. A cellular fluorescent PLA2 assay showed that hVPLA2
      had a lipolytic action first on the outer plasma membrane and then on the
      perinuclear region. hVPLA2 also caused the translocation of 5-lipoxygenase from
      the cytosol to the nuclear membrane and a 2-fold increase in 5-lipoxygenase
      activity. However, hVPLA2 induced neither the increase in intracellular calcium
      concentration nor cPLA2 phosphorylation; consequently, cPLA2 activity was not
      affected by hVPLA2. Pharmacological inhibition of cPLA2 and the hVPLA2-induced
      activation of eosinophils derived from the cPLA2-deficient mouse corroborated
      that hVPLA2 mediates the release of AA and leukotriene in a cPLA2-independent
      manner. As such, this study represents a unique example in which a secretory
      phospholipase induces the eicosanoid formation in inflammatory cells, completely
      independent of cPLA2 activation.

PMID- 12796498
TI  - Coexistence of group I and group II chaperonins in the archaeon Methanosarcina
      mazei.
AB  - Two distantly related classes of cylindrical chaperonin complexes assist in the
      folding of newly synthesized and stress-denatured proteins in an ATP-dependent
      manner. Group I chaperonins are thought to be restricted to the cytosol of
      bacteria and to mitochondria and chloroplasts, whereas the group II chaperonins
      are found in the archaeal and eukaryotic cytosol. Here we show that members of
      the archaeal genus Methanosarcina co-express both the complete group I
      (GroEL/GroES) and group II (thermosome/prefoldin) chaperonin systems in their
      cytosol. These mesophilic archaea have acquired between 20 and 35% of their genes
      by lateral gene transfer from bacteria. In Methanosarcina mazei Go1, both
      chaperonins are similarly abundant and are moderately induced under heat stress.
      The M. mazei GroEL/GroES proteins have the structural features of their bacterial
      counterparts. The thermosome contains three paralogous subunits, alpha, beta, and
      gamma, which assemble preferentially at a molar ratio of 2:1:1. As shown in
      vitro, the assembly reaction is dependent on ATP/Mg2+ or ADP/Mg2+ and the
      regulatory role of the beta subunit. The co-existence of both chaperonin systems
      in the same cellular compartment suggests the Methanosarcina species as useful
      model systems in studying the differential substrate specificity of the group I
      and II chaperonins and in elucidating how newly synthesized proteins are sorted
      from the ribosome to the proper chaperonin for folding.

PMID- 12796499
TI  - Two waves of platelet secretion induced by thromboxane A2 receptor and a critical
      role for phosphoinositide 3-kinases.
AB  - Thromboxane A2 (TXA2)-mediated platelet secretion and aggregation are important
      in thrombosis. Here, we present a novel finding that the stable TXA2 analogue,
      U46619, induces two waves of platelet secretion, each of which precedes a
      distinct wave of platelet aggregation. ADP released from platelets during the
      first wave of secretion played a major role in augmenting the first wave of
      platelet aggregation. The second wave of platelet secretion and aggregation
      required the first wave of both ADP secretion and aggregation and were blocked by
      either the integrin inhibitor RGDS or a P2Y12 receptor antagonist, indicating a
      requirement for both the integrin outside-in signal and ADP-activated Gi pathway.
      U46619 stimulated phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of
      Akt, which was augmented by ADP but did not require integrin outside-in
      signaling. Platelets from PI3Kgamma knock-out mice or PI3K inhibitor-treated
      platelets showed an impaired second wave of platelet secretion and aggregation.
      However, the second wave of platelet aggregation was restored by addition of
      exogenous ADP to PI3Kgamma deficient or PI3K inhibitor-treated platelets. Thus,
      our data indicate that PI3K, together with the integrin outside-in signaling,
      play a central role in inducing the second wave of platelet secretion, which
      leads to the second wave of irreversible platelet aggregation.

PMID- 12796500
TI  - A 16-residue peptide fragment of macrophage migration inhibitory factor, MIF-(50
      65), exhibits redox activity and has MIF-like biological functions.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine that participates in
      the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein
      oxidoreductase activity of MIF is associated with certain biological functions.
      Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some
      biochemical properties of the full-length protein. We report on the
      characterization of CXXC-spanning MIF-(50-65) and its serine variant, C57S/C60S
      MIF-(50-65). Following disulfide-mediated cyclization, MIF-(50-65) adapted a beta
      turn conformation comparable with that of beta-turn-containing cyclo-57,60
      [Asp57,Dap60]MIF-(50-65). MIF-(50-65) had a redox potential E'0 of -0.258 V and
      formed mixed disulfides with glutathione and cysteine. MIF-(50-65) but not
      C57S/C60S-MIF-(50-65) had oxidoreductase activity in vitro. Intriguingly, MIF-(50
      65) exhibited MIF-like cellular activities. The peptide but not its variant had
      glucocorticoid overriding and proliferation-enhancing activity and stimulated
      ERK1/2 phosphorylation. MIF-(50-65) and its variant bound to the MIF-binding
      protein JAB1 and enhanced cellular levels of p27Kip1. As the peptide and its
      variant were endocytosed at similar efficiency, sequence 50-65 appears sufficient
      for the JAB1-related effects of MIF, whereas other activities require CXXC. Cyclo
      57,60-[Asp57,Dap60]MIF-(50-65) activated ERK1/2, indicating that CXXC-dependent
      disulfide and beta-turn formation is associated with an activity-inducing
      conformation. We conclude that CXXC and sequence 50-65 are critical for the
      activities of MIF. MIF-(50-65) is a surprisingly short sequence with MIF-like
      functions that could be an excellent molecular template for MIF therapeutics.

PMID- 12796501
TI  - Insulin induces the expression of the SHARP-2/Stra13/DEC1 gene via a
      phosphoinositide 3-kinase pathway.
AB  - Transcription of the rat fatty acid synthase (FAS) gene in the rat liver can be
      regulated by feeding a high carbohydrate diet. A carbohydrate response element
      (ChoRE) located on the rat FAS gene promoter has been identified. Using multiple
      copies of the ChoRE as the bait in a yeast one-hybrid system, a rat liver cDNA
      library was screened, and the cDNA of ChoRE-binding proteins was cloned. A
      positive clone that encodes a basic helix-loop-helix protein, enhancer of split-
      and hairy-related protein-2 (SHARP-2), was obtained. Northern blot analysis
      revealed that the levels of SHARP-2 mRNA increase when a high carbohydrate diet
      is fed to normal rats or when insulin is administered to diabetic rats. In
      primary cultured rat hepatocytes, insulin rapidly induced an accumulation of
      SHARP-2 mRNA even in the absence of glucose. A time course for the increase in
      SHARP-2 mRNA levels indicated that it followed by those of FAS and L-type
      pyruvate kinase mRNAs and that the initial time course of SHARP-2 mRNA was
      similar to changes in the levels of glucokinase mRNA and phosphoenolpyruvate
      carboxykinase mRNA. Although wortmannin, LY294002, and actinomycin D blocked the
      increase in SHARP-2 mRNA levels by insulin, rapamycin, staurosporine, PD98059,
      okadaic acid, and 8-bromocyclic AMP had no effect. In addition, nuclear run-on
      assay revealed that transcription of the rat SHARP-2 gene was induced by insulin.
      Thus, we conclude that insulin induces the transcription of the rat SHARP-2 gene
      via a phosphoinositide 3-kinase pathway.

PMID- 12796502
TI  - Podocan, a novel small leucine-rich repeat protein expressed in the sclerotic
      glomerular lesion of experimental HIV-associated nephropathy.
AB  - Growing evidence suggests that human immunodeficiency virus (HIV)-1 infection of
      podocytes plays a central role in the glomerular disease of HIV-associated
      nephropathy (HIVAN). As an approach to identify host genes involved in the
      pathogenesis of the sclerotic glomerular lesion in HIVAN, representational
      difference analysis of cDNA was used to identify differentially expressed genes
      in HIV-1 transgenic and nontransgenic podocytes. We isolated a novel member of
      the small leucine-rich repeat (SLR) protein family, podocan, that is expressed at
      high levels in the HIV-1 transgenic podocytes. In normal embryonic kidney, a 3.2
      kb podocan transcript was detected at low levels, and expression increased
      dramatically within 24 h following birth. Expression of a 2.3-kb transcript
      became evident after birth and gradually increased to 50% of the total podocan
      RNA in the mature kidney. Phylogenetically, podocan represents a new class in the
      SLR protein gene family, an expanding protein family sharing homology with the
      small leucine-rich repeat proteoglycans. The 3.2-kb transcript encodes a
      predicted 611-amino acid secretory protein with 20 leucine-rich repeats, a unique
      N-terminal cysteine-rich cluster pattern and a highly acidic C-terminal domain.
      In situ hybridization of normal kidney revealed podocan mRNA expression in
      podocytes and likely vascular endothelial cells within the glomerulus. The
      immunohistochemical staining pattern of podocan protein in normal kidney
      glomeruli was consistent with that of the glomerular basement membrane, and
      staining was markedly increased in sclerotic glomerular lesions in the transgenic
      HIVAN model. Thus, podocan defines a new class within the SLR protein family and
      is a previously unrecognized component of the sclerotic glomerular lesion that
      develops in the course of experimental HIVAN.

PMID- 12796503
TI  - Activation mechanism of the CO sensor CooA. Mutational and resonance Raman
      spectroscopic studies.
AB  - CooA is a CO-dependent heme protein transcription factor of the bacterium
      Rhodospirillum rubrum. CO binding to its heme causes CooA to bind DNA and
      activate expression of genes for CO metabolism. To understand the nature of CO
      activation, several CooA mutational variants have been studied by resonance Raman
      spectroscopy, in vivo activity measurements, and DNA binding assays. Analysis of
      the Fe-C and C-O stretching Raman spectroscopy bands permits the conclusion that
      when CO displaces the Pro2 heme ligand, the protein forms a hydrophobic pocket in
      which the C-helix residues Gly117, Leu116, and Ile113 are close to the bound CO.
      The displaced Pro2 terminus is expelled from this pocket, unless the pH is raised
      above the pKa, in which case the terminus remains in H-bond contact. The pKa for
      this transition is 8.6, two units below that of aqueous proline, reflecting the
      hydrophobic nature of the pocket. The proximal Fe-His bond in Fe[II]CooA is as
      strong as it is in myoglobin but is weakened by CO binding, an effect
      attributable to loss of an H-bond from the proximal His77 ligand to the adjacent
      Asn42 side chain. A structural model is proposed for the position of the CO-bound
      heme in the active form of CooA, which has implications for the mechanism of CO
      activation.

PMID- 12796504
TI  - Sphingosine 1-phosphate in amniotic fluid modulates cyclooxygenase-2 expression
      in human amnion-derived WISH cells.
AB  - The metabolism of arachidonic acid, in particular the generation of
      prostaglandins (PGs), has been proposed to play a key role in the regulation of
      labor. Moreover, several extracellular proteins have been reported to modulate PG
      synthesis in amnion cells. In this study, we found that lipid components
      dissolved in the amniotic fluid modulate PG synthesis in WISH human amnion cells
      and identified one of these components as a sphingosine 1-phosphate (S1P). WISH
      cells express several S1P receptors including S1P1, S1P2, and S1P3. When WISH
      cells were stimulated with S1P, PGE2 synthesis increased in a concentration
      dependent manner, showing maximal activity at around 100 nM. S1P treatment also
      caused the up-regulation of cyclooxygenase-2 (COX-2) mRNA and protein, which was
      apparent within 3-12 h of stimulation. In terms of the intracellular signaling
      pathway of S1P-induced WISH cell activation, we found that S1P stimulated two
      kinds of MAPK, ERK, and p38 kinase. We examined the roles of these two MAPKs in
      S1P-induced COX-2 expression. S1P-induced COX-2 expression was blocked completely
      by PD-98059 but not by SB-203580, suggesting that ERK has a critical role in the
      process. Transfection of S1P1 or S1P3 but not of S1P2 antisense oligonucleotide
      inhibited S1P-induced COX-2 expression and PGE2 production in WISH cells,
      indicating the involvements of S1P1 and S1P3 in the processes. This study
      demonstrates the physiological role of S1P in amniotic fluid and its effect on
      the modulation of COX-2 expression and PGs synthesis in WISH cells.

PMID- 12796505
TI  - Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to
      lithium. Evidence for autoregulation of GSK-3.
AB  - Glycogen synthase kinase-3 (GSK-3) is a critical, negative regulator of diverse
      signaling pathways. Lithium is a direct inhibitor of GSK-3 and has been widely
      used to test the putative role of GSK-3 in multiple settings. However, lithium
      also inhibits other targets, including inositol monophosphatase and structurally
      related phosphomonoesterases, and thus additional approaches are needed to
      attribute a given biological effect of lithium to a specific target. For example,
      lithium is known to increase the inhibitory N-terminal phosphorylation of GSK-3,
      but the target of lithium responsible for this indirect regulation has not been
      identified. We have characterized a short peptide derived from the GSK-3
      interaction domain of Axin that potently inhibits GSK-3 activity in vitro and in
      mammalian cells and robustly activates Wnt-dependent transcription, mimicking
      lithium action. We show here, using the GSK-3 interaction domain peptide, as well
      as small molecule inhibitors of GSK-3, that lithium induces GSK-3 N-terminal
      phosphorylation through direct inhibition of GSK-3 itself. Reduction of GSK-3
      protein levels, either by RNA interference or by disruption of the mouse GSK
      3beta gene, causes increased N-terminal phosphorylation of GSK-3, confirming that
      GSK-3 regulates its own phosphorylation status. Finally, evidence is presented
      that N-terminal phosphorylation of GSK-3 can be regulated by the GSK-3-dependent
      protein phosphatase-1.inhibitor-2 complex.

PMID- 12796506
TI  - 1Hepatitis C virus NS5A protein modulates c-Jun N-terminal kinase through
      interaction with tumor necrosis factor receptor-associated factor 2.
AB  - The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a
      phosphoprotein possessing various functions. We have previously reported that the
      HCV NS5A protein interacts with tumor necrosis factor (TNF) receptor-associated
      factor (TRAF) domain of TRAF2 (Park, K.-J., Choi, S.-H., Lee, S. Y., Hwang, S.
      B., and Lai, M. M. C. (2002) J. Biol. Chem. 277, 13122-13128). Both TNF-alpha-
      and TRAF2-mediated nuclear factor-kappaB (NF-kappaB) activations were inhibited
      by NS5A-TRAF2 interaction. Because TRAF2 is required for the activation of both
      NF-kappaB and c-Jun N-terminal kinase (JNK), we investigated HCV NS5A protein for
      its potential capacity to modulate TRAF2-mediated JNK activity. Using in vitro
      kinase assay, we have found that NS5A protein synergistically activated both TNF
      alpha- and TRAF2-mediated JNK in human embryonic kidney 293T cells. Furthermore,
      synergism of NS5A-mediated JNK activation was inhibited by dominant-negative form
      of MEK kinase 1. Our in vivo binding data show that NS5A does not inhibit
      interaction between TNF receptor-associated death domain and TRAF2 protein,
      indicating that NS5A and TRAF2 may form a ternary complex with TNF receptor
      associated death domain. These results indicate that HCV NS5A protein modulates
      TNF signaling of the host cells and may play a role in HCV pathogenesis.

PMID- 12796507
TI  - A globin in the nucleus!
AB  - Cytoglobin and neuroglobin are recently discovered members of the globin family.
      In situ hybridization localized neuroglobin mainly in brain and retina, while
      cytoglobin was expressed ubiquitously in all analyzed tissues. In the present
      study, polyclonal antibodies were raised against both proteins and the
      distribution of them was studied by immunocytochemistry at tissue and subcellular
      level. Cytoglobin immunoreactivity was uniformly distributed and found in all
      tissues studied. At the subcellular level, cytoglobin immunoreactivity was
      exclusively detected in the cell nucleus. In contrast, neuroglobin
      immunoreactivity was detected in specific brain regions with varying intensities
      and in the islet of Langerhans in the pancreas. The immunoreactivity was
      restricted to the cytoplasm of neurons and endocrine beta cells. The nuclear
      localization of cytoglobin opens new perspectives for possible function(s) of
      globin-folded proteins as transcriptional regulators.

PMID- 12796508
TI  - The terminal nucleotide of the Mu genome controls catalysis of DNA strand
      transfer.
AB  - Members of the transposase/retroviral-integrase superfamily use a single active
      site to perform at least two reactions during transposition of a DNA transposon
      or a retroviral cDNA. They hydrolyze a DNA sequence at the end of the mobile DNA
      and then join this DNA end to a target DNA (a reaction called DNA strand
      transfer). Critical to understanding the mechanism of recombination is
      elucidating how these distinct reactions are orchestrated by the same active
      site. Here we find that DNA substrates terminating in a dideoxynucleotide allow
      Mu transposase to hydrolyze a target DNA, combining aspects of both natural
      reactions. Analyses of the sequence preferences for target hydrolysis and of the
      structure of the cleaved product indicate that this reaction is promoted by the
      active site in the conformation that normally promotes DNA strand transfer.
      Dissecting the DNA requirements for target hydrolysis reveals that the ribose of
      the last nucleotide of the Mu DNA activates transposase's catalytic potential,
      even when this residue is not a direct chemical participant. These findings
      provide insight into the molecular mechanism insuring that DNA strand transfer
      ordinarily occurs rather than inappropriate DNA cleavage. The required presence
      of the terminal nucleotide in the transposase active site creates a great
      advantage for the attached 3'OH to serve as nucleophile.

PMID- 12796509
TI  - Nutrient loading and consumers: agents of change in open-coast macrophyte
      assemblages.
AB  - Human activities are significantly altering nutrient regimes and the abundance of
      consumers in coastal ecosystems. A field experiment in an open-coast, upwelling
      ecosystem showed that small increases in nutrients increased the biomass and
      evenness of tide pool macrophytes where consumer abundance and nutrient loading
      rates were low. Consumers, when abundant, had negative effects on the diversity
      and biomass of macrophytes. Nutrient loading increases and consumers are less
      abundant and efficient as wave exposure increases along open coastlines.
      Experimentally reversing the natural state of nutrient supply and consumer
      pressure at a wave-protected site to match wave-exposed sites caused the
      structure of the macrophyte assemblage to converge on that found naturally in
      wave-exposed pools. The increases in evenness and abundance were driven by
      increases in structurally complex functional groups. In contrast, increased
      nutrient loading in semienclosed marine or estuarine ecosystems is typically
      associated with declines in macrophyte diversity because of increases in
      structurally simple and opportunistic functional groups. If nutrient
      concentration of upwelled waters changes with climatic warming or increasing
      frequency of El Ninos, as predicted by some climate models, these results suggest
      that macrophyte abundance and evenness along wave-swept open-coasts will also
      change. Macrophytes represent a significant fraction of continental shelf
      production and provide important habitat for many marine species. The combined
      effects of shifting nutrient regimes and overexploitation of consumers may have
      unexpected consequences for the structure and functioning of open-coast
      communities.

PMID- 12796510
TI  - Connectivity optimization and the positioning of cortical areas.
AB  - By examining many alternative arrangements of cortical areas, we have found that
      the arrangement actually present in the brain minimizes the volume of the axons
      required for interconnecting the areas. Our observations support the notion that
      the organization of cortical areas has evolved to optimize interareal
      connections.

PMID- 12796511
TI  - Relationship of herpes simplex virus genome configuration to productive and
      persistent infections.
AB  - Infection of susceptible cells by herpes simplex virus (HSV) can lead to
      productive infection or to latency, where the genomes persist in the nuclei of
      peripheral neurons in a quiescent state. Using the HSV strain d109, which does
      not express any viral genes and thus establishes a quiescent state in most cells,
      we observed that a fraction of genomes circularized upon infection. The
      expression of infected cell protein (ICP) 0, which is known to be involved in
      reactivation from latency and the promotion of productive infection, inhibited
      the formation of circular genomes. Circular genomes were not observed upon
      infection of fully permissive cells by wild-type virus, in either the presence or
      absence of viral DNA replication. However, productive infection in the absence of
      ICP0 resulted in the accumulation of a subpopulation of circular genomes. The
      proportion of circular genomes formed during infection with an ICP0 mutant was
      greater at low multiplicity of infection, a condition in which ICP0 mutants
      replicate poorly. In the complete absence of viral gene expression, it was found
      that only circular genomes persisted in cells. These results suggest that
      circularization of the HSV genome may not occur early in the productive phase of
      wild-type HSV infection, but rather during establishment of a quiescent state or
      latency, providing a possible strategy for long-term persistence. Additionally,
      the circularization and possible fate of HSV genomes are regulated by an activity
      of ICP0.

PMID- 12796512
TI  - Mast cells disrupt epithelial barrier function during enteric nematode infection.
AB  - We have investigated the influence of mast cells on the barrier function of
      intestinal epithelium during nematode infection. Trichinella spiralis infection
      induces a strong type 2 cytokine-mediated inflammation, resulting in a critical
      mucosal mastocytosis that is known to mediate expulsion of the parasites from the
      intestine. The host response to infection is also characterized by an increase in
      mucosal leakiness. We show here that intestinal epithelial permeability is
      markedly elevated during infection, with kinetics that mirror the adaptive immune
      response to primary and secondary infection. Furthermore, we have identified
      degradation of the tight junction protein, occludin, thereby providing a
      mechanism for increased paracellular permeability during helminth infection. We
      further demonstrate by using anti-c-kit antibody and IL-9 transgenic mice that
      mast cells are directly responsible for increasing epithelial paracellular
      permeability and that mice deficient in a mast cell-specific protease fail to
      increase intestinal permeability and fail to expel their parasite burden. These
      results provide the mechanism whereby mucosal mast cells mediate parasite
      expulsion from the intestine.

PMID- 12796513
TI  - Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis.
AB  - The RUNX transcription factors are important regulators of lineage-specific gene
      expression. RUNX are bifunctional, acting both as activators and repressors of
      tissue-specific target genes. Recently, we have demonstrated that Runx3 is a
      neurogenic transcription factor, which regulates development and survival of
      proprioceptive neurons in dorsal root ganglia. Here we report that Runx3 and
      Runx1 are highly expressed in thymic medulla and cortex, respectively, and
      function in development of CD8 T cells during thymopoiesis. Runx3-deficient
      (Runx3 KO) mice display abnormalities in CD4 expression during lineage decisions
      and impairment of CD8 T cell maturation in the thymus. A large proportion of
      Runx3 KO peripheral CD8 T cells also expressed CD4, and in contrast to wild-type,
      their proliferation ability was largely reduced. In addition, the in vitro
      cytotoxic activity of alloimmunized peritoneal exudate lymphocytes was
      significantly lower in Runx3 KO compared with WT mice. In a compound mutant
      mouse, null for Runx3 and heterozygous for Runx1 (Runx3-/-;Runx1+/-), all
      peripheral CD8 T cells also expressed CD4, resulting in a complete lack of single
      positive CD8+ T cells in the spleen. The results provide information on the role
      of Runx3 and Runx1 in thymopoiesis and suggest that both act as transcriptional
      repressors of CD4 expression during T cell lineage decisions.

PMID- 12796514
TI  - Spreading of Sir3 protein in cells with severe histone H3 hypoacetylation.
AB  - Heterochromatin formation in yeast involves deacetylation of histones, but the
      precise relationship between acetylation and the association of proteins such as
      Sir3, Sir4, and the histone deacetylase Sir2 with chromatin is still unclear.
      Here we show that Sir3 protein spreads to subtelomeric DNA in cells lacking the
      transcription-related histone acetyltransferases GCN5 and ELP3. Spreading
      correlates with hypoacetylation of lysines in the histone H3 tail and results in
      deacetylation of lysine 16 in histone H4. De-repression of genes situated very
      close to the ends of the chromosomes in gcn5 elp3 suggests that Sir3 spreads into
      subtelomeric DNA from the tip of the telomere. Interestingly, growth defects
      caused by gcn5 elp3 mutation can be suppressed by SIR deletion, suggesting that
      Sir proteins become detrimental for growth when chromatin is severely
      hypoacetylated.

PMID- 12796516
TI  - Clinical trials of antiepileptic medications in newly diagnosed patients with
      epilepsy.
AB  - Results from add-on antiepileptic drug (AED) trials performed in patients with
      chronic refractory epilepsy cannot be directly extrapolated to newly diagnosed
      patients because of fundamental differences in disease characteristics between
      the two patient populations. This article reviews the results of randomized,
      controlled trials of AEDs as monotherapy in newly diagnosed patients, focusing on
      the newer drugs. None of the newer AEDs has shown superior efficacy when tested
      against established agents for the treatment of partial seizures and generalized
      tonic-clonic seizures, the most common seizure types. Some of the newer drugs
      have shown good tolerability, resulting in better overall effectiveness in the
      case of lamotrigine over carbamazepine and oxcarbazepine over phenytoin, whereas
      vigabatrin and remacemide were demonstrated to have inferior efficacy compared
      with carbamazepine. The difficulty in detecting differences in efficacy among the
      AEDs might be attributed to the strategies underlying their development and the
      characteristics of the patient population under investigation. A better
      understanding of the pathophysiology of seizures and its relationship to
      epileptogenesis, and the use of more innovative strategies to identify new
      molecular targets, are needed for the development of a new generation of more
      effective AEDs that are not merely antiseizure but will hinder or reverse the
      deleterious processes that underlie the genesis of refractory epilepsy.

PMID- 12796515
TI  - RNA recognition by designed peptide fusion creates "artificial" tRNA synthetase.
AB  - The genetic code was established through aminoacylations of RNA substrates that
      emerged as tRNAs. The 20 aminoacyl-tRNA synthetases (one for each amino acid) are
      ancient proteins, the active-site domain of which catalyzes formation of an
      aminoacyl adenylate that subsequently reacts with the 3' end of bound tRNA.
      Binding of tRNA depends on idiosyncratic (to the particular synthetase) domains
      and motifs that are fused to or inserted into the conserved active-site domain.
      Here we take the domain for synthesis of alanyl adenylate and fuse it to
      "artificial" peptide sequences (28 aa) that were shown previously to bind to the
      acceptor arm of tRNAAla. Certain fusions confer aminoacylation activity on
      tRNAAla and on hairpin microhelices modeled after its acceptor stem.
      Aminoacylation was sensitive to the presence of a specific G:U base pair known to
      be a major determinant of tRNAAla identity. Aminoacylation efficiency and
      specificity also depended on the specific peptide sequence. The results
      demonstrate that barriers to RNA-specific aminoacylations are low and can be
      achieved by relatively simple peptide fusions. They also suggest a paradigm for
      rationally designed specific aminoacylations based on peptide fusions.

PMID- 12796517
TI  - Conversion to monotherapy: clinical trials in patients with refractory partial
      seizures.
AB  - The efficacy, tolerability, and safety of a potential antiepileptic drug (AED)
      are initially evaluated in clinical trials employing add-on designs. When
      positive, those trials allow us only to conclude that the study drug is
      efficacious when administered as adjunctive therapy. However, to demonstrate
      efficacy and safety as monotherapy, the drug must be evaluated using a
      monotherapy trial design. Such a design needs to take into account important
      methodologic issues that can affect clinical relevance and/or raise ethical
      concerns. This review critically assesses two monotherapy trial designs:
      outpatient conversion to monotherapy and presurgical conversion to monotherapy in
      patients with medically refractory seizures of partial onset. The efficacy and
      safety data derived from published studies of AED monotherapy in patients with
      partial-onset seizures that utilize these trial designs are evaluated and the
      advantages and disadvantages of each trial design are discussed.

PMID- 12796518
TI  - Limitations of monotherapy trials in epilepsy.
AB  - Monotherapy is considered optimal management for most patients with epilepsy, but
      designing monotherapy trials in epilepsy has proved to be a complex endeavor.
      Consideration of the validity of evidence for efficacy, potential risks to
      patients, clinical applicability of results, and effects of dosing and titration
      rates on efficacy and tolerability creates unique challenges. This article
      reviews pertinent aspects of trials of conversion to monotherapy in refractory
      patients and equivalence trials in newly diagnosed patients to better understand
      their limitations. Despite the inherent difficulties in designing monotherapy
      trials in epilepsy, previous monotherapy studies have provided important
      information for clinical management with new treatments.

PMID- 12796519
TI  - The importance of monotherapy in pregnancy.
AB  - The great majority of women with epilepsy who become pregnant have normal
      pregnancies and healthy infants. However, in utero exposure to antiepileptic
      drugs (AEDs) can put infants of women with epilepsy at increased risk for a
      variety of abnormalities, including intrauterine growth retardation, minor
      anomalies, major congenital malformations, microcephaly, and cognitive
      dysfunction. Various combinations of these findings can occur in an individual
      infant and are referred to as the fetal anticonvulsant syndrome (FAS). The most
      common major malformations are cleft lip/palate, heart defects, neural tube
      defects, and urogenital defects. Although AEDs have teratogenic risks, withdrawal
      of all AEDs before pregnancy is not a realistic option for many women with
      epilepsy. The results of several studies indicate that AED monotherapy reduces
      the risk for development of FAS compared with polytherapy exposure in utero.
      Current treatment guidelines advise use of AED monotherapy when possible and
      folate supplementation beginning before and continuing throughout pregnancy.
      Prenatal screening for major malformations should be offered. Careful planning
      and management of any pregnancy in women with epilepsy is essential to increase
      the likelihood of a healthy outcome for mother and infant.

PMID- 12796520
TI  - Blind men and blinking elephants.

PMID- 12796521
TI  - Prism adaptation treatment of neglect: conflicting results?

PMID- 12796522
TI  - Strokes, thromboembolic events, and IVIg: rare incidents blemish an excellent
      safety record.

PMID- 12796523
TI  - Striatal activation during blepharospasm revealed by fMRI.
AB  - OBJECTIVE: To investigate brain areas involved in the initiation and execution of
      eyelid spasm in patients with benign essential blepharospasm. METHODS: The
      authors used fMRI and correlated the blood oxygenation level-dependent (BOLD)
      signal with epochs of frequent eyelid spasm in six patients and with epochs of
      voluntary eye blinks in four healthy subjects. RESULTS: Spasm epochs were
      accompanied by activation in a subregion of the putamen in all patients, whereas
      voluntary blinking in healthy subjects was not. Other areas of activation common
      to patients and healthy subjects included frontal and parietal operculum,
      supplementary motor area, primary sensorimotor cortex, various visual areas, and
      the cerebellum. CONCLUSIONS: The striatum may be involved in the initiation or
      execution of eyelid spasm. Future studies, possibly including electromyography
      (EMG) during fMRI, are needed to detect the sequence and role of other
      concomitantly activated areas.

PMID- 12796524
TI  - Effects of levodopa on motor sequence learning in Parkinson's disease.
AB  - BACKGROUND: Dopaminergic therapy with levodopa improves motor function in PD
      patients, but the effects of levodopa on cognition in PD remain uncertain.
      OBJECTIVE: To use H(2)(15)O and PET to assess the effect of levodopa infusion on
      motor sequence learning in PD. METHODS: Seven right-handed PD patients were
      scanned "on" and "off" levodopa while performing a sequence learning task. The
      changes in learning performance and regional brain activation that occurred
      during this intervention were assessed. RESULTS: During PET imaging, levodopa
      infusion reduced learning performance as measured by subject report (p < 0.05).
      This behavioral change was accompanied by enhanced activation during treatment in
      the right premotor cortex and a decline in the ipsilateral occipital association
      area (p < 0.01). Levodopa-induced changes in learning-related activation
      responses in the occipital association cortex correlated with changes in learning
      indexes (p < 0.01). CONCLUSIONS: Levodopa treatment appears to have subtle
      detrimental effects on cognitive function in nondemented PD patients. These
      effects may be mediated through an impairment in brain activation in occipital
      association cortex.

PMID- 12796525
TI  - L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism.
AB  - OBJECTIVE: To assess whether polymorphisms in the dopamine receptor genes and in
      the dopamine transporter gene (DAT ) are predictors of adverse effects of L 
      dopa. METHODS: A retrospective noninterventional study with 183 patients with PD
      was conducted. Nine polymorphisms of the dopamine D2 receptor (DRD2 ), two of the
      dopamine D3 receptor (DRD3 ), three of the dopamine D4 receptor (DRD4 ), and one
      variable number of tandem repeats (VNTR) of the DAT were studied. The entire
      coding and promoter regions of the DRD2 gene of 48 patients with early and severe
      appearance of adverse effects from L -dopa treatment and of eight never-afflicted
      patients were sequenced. RESULTS: The polymorphisms of DRD2, DRD3, and DRD4 were
      not associated with the risk to develop adverse effects of L -dopa. However,
      patients with psychosis or dyskinesia carried the nine copy allele 40-bp VNTR of
      the DAT more frequently than nonafflicted patients (60.0 vs 36.8%, p = 0.008; and
      54.7 vs 32.9%, p = 0.006). Sequencing of the DRD2 gene revealed no new mutation,
      with the exception of one silent mutation in exon 6. CONCLUSIONS: Genetic
      variations of the DRD2, DRD3, and DRD4 do not influence the occurrence of L -dopa
      induced adverse effects. However, the nine copy allele 40-bp VNTR of the DAT is a
      predictor for the occurrence of psychosis or dyskinesia in L -dopa-treated
      patients.

PMID- 12796526
TI  - Longitudinal outcome of Parkinson's disease patients with psychosis.
AB  - OBJECTIVES: To examine the long-term outcome of PD patients with psychosis
      requiring antipsychotic therapy; to explore predictors of mortality, nursing home
      placement, dementia, and persistent psychosis; and to compare outcomes of those
      with persistent psychosis vs those whose psychosis resolved. METHODS: Baseline
      data available from 59 patients enrolled in the PSYCLOPS (PSychosis and CLOzapine
      in PD Study) trial included age, age at onset of PD, duration of PD and
      psychosis, character of psychosis, medications, living setting, and scores for
      Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale,
      Hoehn and Yahr Scale, and Clinical Global Impression Scale. Longitudinal data
      were collected 26 months later regarding four outcomes: death, nursing home
      placement, diagnosis of dementia, and persistence of psychosis. Logistic
      regression was used to explore whether any baseline characteristics were
      associated with an increased likelihood of one of these outcomes. RESULTS: At
      baseline, 56% of patients had an MMSE score of <25, 12% were in a nursing home,
      95% had hallucinations, and 60% had paranoia. On follow-up, 25% were dead,
      nursing home placement occurred in 42%, psychosis was persistent in 69%, and
      dementia was diagnosed in 68%. Select baseline characteristics predicted
      individual outcomes: Nursing home placement was associated with the presence of
      paranoia and older age; persistent psychosis was associated with younger age at
      onset of PD and longer disease duration; dementia was associated with older age
      at PD onset and lower initial MMSE score; no characteristics predicted death.
      Whether psychosis persisted or not had no significant effect on the development
      of the other three outcomes. The prevalence of hallucinations at follow-up was
      not different between groups currently receiving antipsychotics vs those on no
      treatment. CONCLUSIONS: Psychosis in PD requiring antipsychotic therapy is
      frequently associated with death, nursing home placement, development and
      progression of dementia, and persistence of psychosis. Still, it appears the
      prognosis has improved with atypical antipsychotic therapy based on the finding
      that 28% of NH patients died within 2 years compared with 100% in a previous
      study done prior to availability of this treatment.

PMID- 12796527
TI  - Parkinson's disease risks associated with dietary iron, manganese, and other
      nutrient intakes.
AB  - BACKGROUND: Dietary influences on oxidative stress have been thought to play
      important role in the etiology of PD. OBJECTIVE: To examine associations of PD
      with dietary nutrients, including minerals, vitamins, and fats. METHODS: A
      population-based case-control study was conducted among newly diagnosed case (n =
      250) and control subjects (n = 388) identified between 1992 and 2002 from
      enrollees of the Group Health Cooperative health maintenance organization in
      western Washington state. Controls were frequency matched to cases on sex and
      age. In-person interviews elicited data on food frequency habits during most of
      adult life. Nutrient intakes were calculated and analyzed by adjusting each
      person's nutrient intake by their total energy intake (the nutrient density
      technique). RESULTS: Subjects with an iron intake in the highest quartile
      compared with those in the lowest quartile had an increased risk of PD (odds
      ratio = 1.7, 95% CI: 1.0, 2.7, trend p = 0.016). There was an apparent joint
      effect of iron and manganese; dietary intake above median levels of both together
      conferred a nearly doubled risk compared with lower intakes of each nutrient
      (odds ratio = 1.9, 95% CI: 1.2, 2.9). No strong associations were found for
      either antioxidants or fats. CONCLUSION: A high intake of iron, especially in
      combination with high manganese intake, may be related to risk for PD.

PMID- 12796528
TI  - Atrophy of superior cerebellar peduncle in progressive supranuclear palsy.
AB  - BACKGROUND: Pathologic changes in the superior cerebellar peduncles (SCP) are
      common in progressive supranuclear palsy (PSP), but atrophy of the SCP has never
      been systematically studied. OBJECTIVE: To investigate the SCP width in PSP cases
      and controls with morphometric methods. METHODS: The mean width of the SCP in
      transverse sections of the pons at the level of trigeminal nerve was determined
      in 48 PSP cases (29 men, 19 women; mean age 72.5 +/- 8.2 years) and 29 age
      matched control subjects, many with neurodegenerative disorders that can be
      clinically mistaken for PSP. As the origin of the SCP is the cerebellar dentate
      nucleus, correlations were sought between SCP atrophy and severity of grumose
      degeneration in the dentate nucleus. RESULTS: The average width of the SCP was
      less in PSP (range 0.09 to 0.24 cm) than in controls (range 0.21 to 0.43 cm; Mann
      Whitney U test, p < 0.001), including control cases that had been clinically
      misdiagnosed as PSP (range 0.26 to 0.41 cm). Severity of SCP atrophy normalized
      by brain weight correlated with disease duration (Spearman rank order
      correlation, r = 0.367, p = 0.028), suggesting that SCP atrophy is a relatively
      early feature of PSP. No correlation was found between grumose degeneration and
      SCP width. CONCLUSIONS: SCP atrophy is common in PSP and correlates with disease
      duration. Given that measurements of the SCP are within the resolution of MRI, it
      remains to be determined if SCP atrophy can be used as a diagnostic marker of
      PSP.

PMID- 12796529
TI  - Differential effects of surgical sympathetic block on sudomotor and
      vasoconstrictor function.
AB  - OBJECTIVE: To assess the effects of a surgical block of the sympathetic chain at
      the T2 level on vasoconstriction and palmar sweating in patients with palmar
      hyperhidrosis. METHODS: In a prospective study, sympathetic vasoconstriction was
      measured by laser-Doppler imaging and by computer-assisted infrared thermography
      (rewarming kinetics following immersion of both hands in ice water [4 degrees C,
      30 seconds]) in 61 patients with hyperhidrosis preoperatively and 2 days and 3
      months postoperatively. In addition, palmar sweating preoperatively and 3 months
      postoperatively was assessed by quantitative sudometry. RESULTS: Before surgery,
      rewarming kinetics was significantly slower in the patients (n = 61) than in the
      healthy control subjects (n = 28). Two days after the block, baseline skin
      temperature increased by about 5 degrees C, and rewarming was massively
      accelerated in each of the patients. Three months postoperatively, rewarming
      kinetics was still accelerated in 36 hands, was unchanged from the preoperative
      condition in 42, and had worsened in 12. These changes were accompanied by
      parallel alterations of laser-Doppler flux. However, palmar sweating was
      massively reduced in all but one patient, irrespective of the different rewarming
      kinetics. CONCLUSIONS: T2 sympathectomy leads to long-lasting inhibition of
      palmar sweating, which does not correlate to loss of vasoconstriction. Recurrent
      and enhanced vasoconstrictor function 3 months following endoscopic sympathetic
      block has major implications for its use to treat enhanced vasoconstriction.

PMID- 12796530
TI  - Gender, cognitive decline, and risk of AD in older persons.
AB  - BACKGROUND: Cross-sectional studies suggest gender differences in cognitive
      function and risk of AD in older persons. However, longitudinal studies comparing
      change in cognitive function and risk of AD in men and women have had mixed
      results. The authors investigated gender differences in rate of decline for
      different cognitive systems and for risk of developing AD. METHODS: Participants
      were from the Religious Orders Study, a longitudinal, clinical-pathologic study
      of aging and AD in older Catholic nuns, priests, and brothers. Longitudinal data
      were available from 577 older women and 271 older men, who completed an average
      of 5.8 annual evaluations with more than 95% follow-up participation in
      survivors. The evaluations included 21 neuropsychological tests, from which
      summary measures of global cognitive function and 5 functional domains were
      formed, and clinical classification of AD. RESULTS: Random effects models were
      used to analyze change in cognitive function, and proportional hazards models
      were used to assess risk of incident AD. On average, men and women declined in
      all abilities during the 8-year period but did not differ in annual rates of
      change in analyses that controlled for age, education, and initial level of
      cognitive function. Risk of incident AD did not differ between men and women.
      Furthermore, results were unchanged after controlling for possession of the
      apolipoprotein-epsilon4 allele. Duration of estrogen use was related to rate of
      global cognitive decline and visuospatial abilities in women but did not
      influence comparisons between men and women in cognitive decline. CONCLUSIONS:
      The results suggest that patterns of cognitive decline and incidence of AD are
      similar in older men and women.

PMID- 12796531
TI  - Terminal decline in cognitive function.
AB  - BACKGROUND: Impending death is thought to be associated with age-related
      cognitive decline, but this association has not been well studied. METHODS:
      Participants were 763 older Roman Catholic nuns, priests, and brothers without
      dementia at baseline. They completed an average of 5.6 annual evaluations (range
      2 to 9), with >95% follow-up participation in survivors. Each evaluation included
      administration of 19 cognitive function tests from which previously established
      measures of global cognition (mean = 0.108, SD = 0.502) and specific cognitive
      functions were derived. In a series of change point random effects models, the
      average point before death when rate of cognitive decline changed was identified,
      and rates of cognitive decline before and after the optimal change point were
      estimated, controlling for the effects of age, sex, and education. RESULTS: There
      were 122 deaths during the observation period. Those who died had lower global
      cognitive function at baseline than survivors (by 0.103 unit; p = 0.03), and
      beginning about 43 months before death, their annual rate of global cognitive
      decline sharply accelerated from an annual loss of 0.026 to 0.173 unit, a more
      than sixfold increase. Results were comparable in analyses that controlled for
      baseline health and disability. Terminal cognitive decline was evident in nearly
      all of those who died, but at highly variable rates. Remarkably little cognitive
      decline was evident in survivors. Decline in episodic memory, semantic memory,
      working memory, perceptual speed, and visuospatial ability also greatly increased
      about 3 to 6 years prior to death. CONCLUSION: On average, cognitive decline
      sharply accelerates in the last years of life.

PMID- 12796532
TI  - Use of preoperative functional neuroimaging to predict language deficits from
      epilepsy surgery.
AB  - BACKGROUND: Left anterior temporal lobectomy (L-ATL) may be complicated by
      confrontation naming deficits. OBJECTIVE: To determine whether preoperative fMRI
      predicts such deficits in patients with epilepsy undergoing L-ATL. METHODS:
      Twenty-four patients with L-ATL underwent preoperative language mapping with
      fMRI, preoperative intracarotid amobarbital (Wada) testing for language
      dominance, and pre- and postoperative neuropsychological testing. fMRI laterality
      indexes (LIs), reflecting the interhemispheric difference between activated
      volumes in left and right homologous regions of interest, were calculated for
      each patient. Relationships between the fMRI LI, Wada language dominance, and
      naming outcome were examined. RESULTS: Both the fMRI LI (p < 0.001) and the Wada
      test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity
      and 73% specificity in predicting significant naming decline. Both fMRI and the
      Wada test were more predictive than age at seizure onset or preoperative naming
      performance. CONCLUSIONS: Preoperative fMRI predicted naming decline in patients
      undergoing left anterior temporal lobectomy surgery.

PMID- 12796533
TI  - Cognitive performance and MR markers of cerebral injury in cognitively impaired
      MS patients.
AB  - OBJECTIVE: To relate neuropsychological performance to measures of cerebral
      injury in persons with MS selected for cognitive impairment. METHODS:
      Participants were 37 individuals with relapsing-remitting (59.5%) and secondary
      progressive (40.5%) MS. They were tested at baseline as part of a clinical trial
      to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria
      included at least mild cognitive impairment on a verbal learning and memory task.
      A modified Brief Repeatable Battery of Neuropsychological Tests formed the core
      of the behavioral protocol. Neuroimaging measures were central (ventricular)
      cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both
      creatine and choline. RESULTS: A clear, consistent relation was found between
      cognitive and MR measures. Among neuroimaging measures, central atrophy displayed
      the highest correlations with cognition, accounting for approximately half the
      variance in overall cognitive performance. NAA ratios in right hemisphere sites
      displayed larger correlations than those on the left. Multiple regression models
      combining the MR measures accounted for well over half the variance in overall
      cognitive performance. The Symbol Digit Modalities Test was the
      neuropsychological task most strongly associated with the neuroimaging variables.
      CONCLUSIONS: If a strong and stable association can be firmly established between
      cognitive and MR variables in appropriate subsets of MS patients, it might aid in
      the investigation of interventions to enhance cognition and modify the course of
      the disease.

PMID- 12796535
TI  - Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European
      patients.
AB  - BACKGROUND: Mutations in various genes of the neuromuscular junction may cause
      congenital myasthenic syndromes (CMS). Most mutations identified to date affect
      the epsilon-subunit gene of the acetylcholine receptor (AChR), leading to end
      plate AChR deficiency. Recently, three different mutations in the RAPSN gene have
      been identified in four CMS patients with AChR deficiency. OBJECTIVE: To perform
      mutation analysis of the RAPSN gene in patients with sporadic or autosomal
      recessive CMS. METHODS: One hundred twenty CMS patients from 110 unrelated
      families were analyzed for the RAPSN mutation N88K by restriction fragment length
      polymorphism and sequence analysis. RESULTS: In 12 CMS patients from 10
      independent families, RAPSN N88K was identified either homozygous or
      heteroallelic to another missense mutation. Symptoms usually started perinatally
      or in the first years of life. However, one patient did not show any myasthenic
      symptoms before the third decade. Clinical symptoms typically included bilateral
      ptosis, weakness of facial, bulbar, and limb muscles, and a favorable response to
      anticholinesterase treatment. Crisis-like exacerbations with respiratory
      insufficiency provoked by stress, fever, or infections in early childhood were
      frequent. All RAPSN N88K families originate from Central or Western European
      countries. Genotype analysis indicated that they derive from a common ancestor
      (founder). CONCLUSIONS: The RAPSN mutation N88K is a frequent cause of rapsyn
      related CMS in European patients. In general, patients (RAPSN N88K) were
      characterized by mild to moderate myasthenic symptoms with favorable response to
      anticholinesterase treatment. However, severity and onset of symptoms may vary to
      a great extent.

PMID- 12796534
TI  - Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.
AB  - OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations
      in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal
      recessive distal muscular dystrophy that arises from mutations in the dysferlin
      gene. This gene is also mutated in families with limb girdle muscular dystrophy
      2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was
      extracted from the peripheral lymphocytes of the patients. The PCR products of
      each of 55 exons were screened by single strand conformation polymorphism or
      direct sequencing from the PCR fragments. RESULTS: The authors identified 16
      different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese
      patients are distributed along the entire length of the gene. CONCLUSIONS: Four
      mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent
      in this population, accounting for 60% of the mutations in this study. This study
      revealed that the G3370T mutation was associated with milder forms of MM and the
      G3510A mutation was associated with a more severe form.

PMID- 12796537
TI  - Alteration of the striatal dopaminergic system in human narcolepsy.
AB  - Striatal D2/D3 dopaminergic receptors have been proposed to play a role in
      cataplexy. The authors studied the striatal presynaptic dopamine transporter and
      postsynaptic D2-receptors in seven patients with narcolepsy and seven control
      subjects using [123I](N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4
      chlorophenyl)tropane and [123I](S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2
      pyrrolidinyl]methyl)benzamide SPECT. D2-receptor binding was elevated in
      narcolepsy (p = 0.017) and correlated with the frequency of cataplectic and sleep
      attacks (R > or = 0.844, p < or = 0.017). The human striatal dopaminergic system
      is altered in vivo in narcolepsy/cataplexy.

PMID- 12796536
TI  - PIP2 binding residues of Kir2.1 are common targets of mutations causing Andersen
      syndrome.
AB  - BACKGROUND: Mutations in KCNJ2, the gene encoding the inward-rectifying K+
      channel Kir2.1, cause the cardiac, skeletal muscle, and developmental phenotypes
      of Andersen-Tawil syndrome (ATS; also known as Andersen syndrome). Although
      pathogenic mechanisms have been proposed for select mutations, a common mechanism
      has not been identified. METHODS: Seventeen probands presenting with symptoms
      characteristic of ATS were evaluated clinically and screened for mutations in
      KCNJ2. The results of mutation analysis were combined with those from previously
      studied subjects to assess the frequency with which KCNJ2 mutations cause ATS.
      RESULTS: Mutations in KCNJ2 were discovered in nine probands. These included six
      novel mutations (D71N, T75R, G146D, R189I, G300D, and R312C) as well as
      previously reported mutations R67W and R218W. Six probands possessed mutations of
      residues implicated in binding membrane-associated phosphatidylinositol 4,5
      bisphosphate (PIP2). In total, mutations in PIP(2)-related residues accounted for
      disease in 18 of 29 (62%) reported KCNJ2 -based probands with ATS. Also reported
      is that mutation R67W causes the full clinical triad in two unrelated males.
      CONCLUSIONS: The novel mutations corresponding to residues involved in Kir2.1
      channel-PIP2 interactions presented here as well as the overall frequency of
      mutations occurring in these residues indicate that defects in PIP2 binding
      constitute a major pathogenic mechanism of ATS. Furthermore, screening KCNJ2 in
      patients with the complex phenotypes of ATS was found to be invaluable in
      establishing or confirming a disease diagnosis as mutations in this gene can be
      identified in the majority of patients.

PMID- 12796538
TI  - Telomerase reactivation in malignant gliomas and loss of heterozygosity on
      10p15.1.
AB  - An inhibitor of telomerase activity maps to chromosome 10p15.1. A series of 51
      high-grade gliomas was analyzed for loss of heterozygosity (LOH) on chromosome 10
      and for telomerase activity. In univariate analysis, LOH10p (59%) and LOH10q
      (61%) were associated with telomerase activity (55%; p < 0.0001 and p = 0.0006).
      In multivariate analysis, only LOH10p remained statistically related to
      telomerase activity, suggesting that the telomerase repressor gene located on
      10p15.1 is inactivated in high-grade gliomas.

PMID- 12796539
TI  - The clinical features of 16 cases of stroke associated with administration of
      IVIg.
AB  - This report characterizes the clinical features of 16 cases of stroke associated
      with IV immunoglobulin infusions. Fourteen of the strokes occurred within 24
      hours of an infusion and 50% of the patients were receiving IV immunoglobulin for
      the first time. Nine patients had multifocal infarctions. All but one of the
      patients had stroke risk factors.

PMID- 12796540
TI  - Arterial thrombosis induced by IVIg and its treatment with tPA.
AB  - IV immunoglobulin therapy can lead to vascular events through increased serum
      viscosity and possibly other mechanisms. The authors describe the successful use
      of tissue plasminogen activator in three of four patients who developed cerebral
      and peripheral arterial thrombosis after treatment with IV immunoglobulin.

PMID- 12796541
TI  - Eye movements tell only half the story.
AB  - The dramatic improvements of neglect symptoms after prism adaptation (PA) have
      been interpreted as evidence that PA reorganizes higher levels of spatial
      representation. Here the authors demonstrate that while the exploratory eye
      movements of a patient with neglect were clearly shifted toward the left after
      PA, he still showed no awareness for the left side of the stimuli he was now
      actively exploring. PA modulates functions of the parietal lobe, such as eye
      movement control, but fails to influence the underlying mechanisms of neglect.

PMID- 12796542
TI  - Prism adaptation can improve contralesional tactile perception in neglect.
AB  - The authors show that prismatic adaptation can reduce tactile inattention in
      stroke patients with unilateral neglect. Four patients with visuospatial neglect
      and tactile extinction underwent 10-minute application of 20 degrees right
      shifting prismatic lenses during pointing. This improved contralesional tactile
      perception in all patients, even for a task requiring no exploration or spatial
      motor responses. This finding suggests a potential role for prismatic adaptation
      in the rehabilitation of multiple sensory modalities in patients with neglect.

PMID- 12796543
TI  - Simultanagnosia through the eyes of an artist.
AB  - An 87-year-old artist experienced a top-of-the-basilar-artery embolic stroke
      secondary to atrial fibrillation and manifested a visual agnosia. Prior to her
      stroke, she painted scenes solely from memory. During her stroke recovery, her
      serial drawings and paintings revealed selective attention to the left lower
      quadrant, with important aspects of the whole image "clipped," as if missing from
      her internal representation of the whole object. Years later, her artistic
      abilities returned with only minor differences from those prior to her stroke.

PMID- 12796544
TI  - A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia.
AB  - The authors performed an MRI, stereo-EEG, and pathology study on a woman with
      subcortical band heterotopia and partial epilepsy. Clinical manifestations of
      seizures always started when ictal discharges were present in outer and
      heterotopic cortices. Simultaneous activation of both cortices and presence of
      differentiated neurons in the white matter and the heterotopia strongly suggest
      that the cortices were anatomically and functionally interconnected.

PMID- 12796545
TI  - Transient lesion in the splenium of the corpus callosum in an epileptic patient.
AB  - Pathogenesis of a rarely occurring transient, isolated focal lesion of the
      splenium of the corpus callosum in epilepsy patients is uncertain: frequent
      seizures or antiepileptic drug reduction causing ischemia or demyelination is
      possible. The several MRI sequences, including diffusion-weighted imaging, in
      this first case of occipital epilepsy suggest ischemia from rapid carbamazepine
      reduction, frequent seizures, or a combination of both.

PMID- 12796546
TI  - Non-24-hour sleep-wake syndrome following a car accident.
AB  - The authors report the case of a 39-year-old sighted woman who displayed non-24
      hour sleep-wake cycles following a car accident. The phase relationship between
      endogenous circadian markers such as plasma melatonin and 6-sulfatoxymelatonin
      rhythms and self-selected sleep times was abnormal. A laboratory investigation
      indicated that she was sensitive to bright light as a circadian synchronizer. MRI
      and brain CT scans were normal, but microscopic brain damage in the vicinity of
      the suprachiasmatic nucleus or its output pathways is plausible.

PMID- 12796547
TI  - Underestimation of time perception after repetitive transcranial magnetic
      stimulation.
AB  - The right dorsolateral prefrontal cortex (rDLPFC) may be important in time
      perception in humans. In the present study, the authors demonstrate that a
      virtual lesion of the rDLPFC by repetitive transcranial magnetic stimulation
      (rTMS) leads to underestimation of time perception for brief intervals (lasting a
      few seconds) in working memory.

PMID- 12796548
TI  - Different spatial processing for stimulus-centered and body-centered
      representations.
AB  - The authors describe a patient who experienced two successive strokes in the
      right hemisphere. After the first stroke, she showed stimulus-centered left
      neglect confined to right space on a circle discrimination task, which resolved.
      After the second stroke, she showed body-centered left neglect on the same task.
      These observations of two types of left neglect in the same patient suggest there
      are at least two distinct spatial attentional systems in the brain: global and
      focal attentional systems.

PMID- 12796549
TI  - Longitudinal MRI study: the effects of azathioprine in MS patients refractory to
      interferon beta-1b.
AB  - An open-label study was performed to assess the effectiveness of oral
      azathioprine (AZA) on augmenting the response to interferon beta-1b (IFNbeta-1b)
      in patients with treatment-refractory relapsing-remitting MS. Six IFNbeta-1b
      treated MS patients with continued disease activity were studied on IFNbeta-1b
      and AZA therapy for a median period of 15 months. A 69% reduction in the number
      of contrast-enhancing lesions was observed during the combination therapy (p =
      0.002).

PMID- 12796550
TI  - Butyrylcholinesterase and progression of cognitive deficits in dementia with Lewy
      bodies.
AB  - Butyrylcholinesterase is implicated in the pathology of AD. Selective inhibitors
      increase acetylcholine and improve cognitive function in animal models. In
      dementia with Lewy bodies, cholinergic activities are more affected than in AD.
      The authors report a highly significant association between temporal cortex
      butyrylcholinesterase activity and the rate of cognitive decline in a
      prospectively studied, autopsy-confirmed dementia with Lewy bodies series.

PMID- 12796551
TI  - Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.
AB  - Muscle biopsy findings in DM2 have been reported to be similar to those in DM1.
      The authors used myosin heavy chain immunohistochemistry and enzyme
      histochemistry for fiber type differentiation on muscle biopsies. Their results
      show that DM2 patients display a subpopulation of type 2 nuclear clump and other
      very small fibers and, hence, preferential type 2 fiber atrophy in contrast to
      type 1 fiber atrophy in DM1 patients.

PMID- 12796552
TI  - A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS
      overlap syndrome.
AB  - A 13084 A->T missense mutation in the mitochondrial ND5 gene was identified in a
      16-year-old boy affected with a progressive neurodegenerative disorder combining
      features of Leigh and MELAS (mitochondrial encephalomyopathy, lactic acidosis,
      and strokelike episodes) syndromes. Muscle biopsy analysis revealed partial
      complex I deficiency. The mutation presented a variable degree of heteroplasmy in
      the patient's tissues. This finding underlines the contribution of mtDNA-encoded
      complex I subunits in the etiology of complex I deficiency associated with
      encephalopathy.

PMID- 12796553
TI  - Meningioma with pneumosinus dilatans.

PMID- 12796554
TI  - Cervical myelopathy secondary to violent tics of Tourette's syndrome.

PMID- 12796555
TI  - HNPP due to a novel missense mutation of the PMP22 gene.

PMID- 12796556
TI  - Monozygotic twin sisters suffering from cluster headache and migraine without
      aura.

PMID- 12796557
TI  - Going deep to cut the link: cortical disconnection syndrome caused by a thalamic
      lesion.

PMID- 12796558
TI  - MRI changes in status epilepticus.

PMID- 12796560
TI  - Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital
      cardiac arrest.

PMID- 12796561
TI  - Serum potassium level and dietary potassium intake as risk factors for stroke.

PMID- 12796562
TI  - The pentapeptide QYNAD does not block voltage-gated sodium channels.

PMID- 12796563
TI  - A comparison of risk factors for recurrent TIA and stroke in patients diagnosed
      with TIA.

PMID- 12796564
TI  - Randomized, comparative study of interferon beta-1a treatment regimens in MS: the
      EVIDENCE trial.

PMID- 12796565
TI  - Prognosis for seizure recurrence in patients with newly diagnosed
      neurocysticercosis.

PMID- 12796566
TI  - PI 3-kinase-Akt-p70 S6 kinase in hypertrophic responses to leukemia inhibitory
      factor in cardiac myocytes.
AB  - Leukemia inhibitory factor (LIF) is a member of interleukin-6 related cytokines,
      which induces cardiac hypertrophy through glycoprotein (gp) 130. In this study,
      the role of phosphatidylinositol (PI) 3-kinase, Akt/protein kinase B (Akt/PKB),
      and p70 S6 kinase activation in LIF-induced hypertrophic responses such as
      stimulation of protein synthesis, atrial natriuretic peptide (ANP) gene
      expression, and reorganization of actin filaments into sarcomeric units was
      investigated in cultured cardiac myocytes. Treatment of cells with LIF resulted
      in sequential activation of PI 3-kinase, Akt/PKB, and p70 S6 kinase. Using
      inhibitors for PI 3-kinase and p70 S6 kinase activation, and adenovirus-mediated
      expression of dominant negative mutants of PI 3-kinase and Akt/PKB, we showed
      that PI 3-kinase activation was essential for stimulation of protein synthesis,
      ANP gene expression, and sarcomeric reorganization induced by LIF, while Akt/PKB
      activation was indispensable for ANP expression and stimulation of protein
      synthesis, but not for sarcomeric reorganization. Activation of p70 S6 kinase was
      necessary for stimulation of protein synthesis, but not for ANP gene expression
      or sarcomeric reorganization. These results indicated the essential role of PI 3
      kinase-Akt/PKB-p70 S6 kinase pathway in the LIF-induced hypertrophic responses in
      cardiac myocytes.

PMID- 12796567
TI  - A case of well-differentiated hepatocellular carcinoma arising in primary biliary
      cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic progressive, autoimmune liver
      disease that increases the risk of hepatobiliary malignancies at a late stage. We
      report a 66-year-old woman with PBC combined with hepatocellular carcinoma (HCC)
      accompanied by hypoglycemia. Two large tumors were detected on admission and the
      patient died because of tumor rupture and subsequent liver failure. Histological
      analysis revealed well-differentiated HCC in both of the tumors. Sometimes the
      patient had suffered from hypoglycemic attacks of unknown origin, but serum
      immunoreactive insulin (IRI) was within the normal range. It was interesting that
      such large well-differentiated hepatocellular carcinomas were generated in PBC.

PMID- 12796568
TI  - Central poorly differentiated adenocarcinoma of the maxilla: report of a case.
AB  - Central adenocarcinoma of the jaws is an extremely rare malignant tumor. We
      reported a case of poorly differentiated adenocarcinoma occurring intraosseously
      in the maxilla. A 62-year-old male was referred to our hospital because of
      swelling of the palate. MRI showed a central tumorous lesion in the maxilla. He
      underwent maxillectomy combined with neck and parapharyngeal dissection.
      Histologic examinations of the surgical specimen revealed poorly differentiated
      adenocaricinoma showing a positive reaction for PAS, CEA and cytokeratin. He
      underwent adjuvant chemotherapy with cis-platinum diamminodichloride, 5
      fluorouracil, and pirarubicin, but he died of multiple distant metastases 7
      months after the surgery.

PMID- 12796569
TI  - Insulin independence following isolated islet transplantation and single islet
      infusions.
AB  - OBJECTIVE: To restore islet function in patients whose labile diabetes subjected
      them to frequent dangerous episodes of hypoglycemic unawareness, and to determine
      whether multiple transplants are always required to achieve insulin independence.
      SUMMARY BACKGROUND DATA: The recent report by the Edmonton group documenting
      restoration of insulin independence by islet transplantation in seven consecutive
      patients with type 1 diabetes differed from previous worldwide experience of only
      sporadic success. In the Edmonton patients, the transplanted islet mass critical
      for success was approximately more than 9,000 IEq/kg of recipient body weight and
      required two or three separate transplants of islets isolated from two to four
      cadaveric donors. Whether the success of the Edmonton group can be recapitulated
      by others, and whether repeated transplants using multiple donors will be a
      universal requirement for success have not been reported. METHODS: The authors
      report their treatment with islet transplantation of nine patients whose labile
      type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia.
      RESULTS: In each of the seven patients who have completed the treatment protocol
      (i.e., one or if necessary a second islet transplant), insulin independence has
      been achieved. In five of the seven patients only a single infusion of islets was
      required. To date, only one recipient has subsequently lost graft function, after
      an initially successful transplant. This patient suffered recurrent hyperglycemia
      9 months after the transplant. CONCLUSIONS: This report confirms the efficacy of
      the Edmonton immunosuppressive regimen and indicates that insulin independence
      can often be achieved by a single transplant of sufficient islet mass.

PMID- 12796570
TI  - Diabetes and hypertension in severe obesity and effects of gastric bypass-induced
      weight loss.
AB  - OBJECTIVE: To evaluate the preoperative relationships of hypertension and
      diabetes mellitus in severe obesity and the effects of gastric bypass (GBP)
      induced weight loss. SUMMARY BACKGROUND DATA: Severe obesity is associated with
      multiple comorbidities, particularly hypertension and type 2 diabetes mellitus,
      that may affect life expectancy. METHODS: The database of patients who had
      undergone GBP by one general surgeon at a university hospital between September
      1981 and January 2000 was queried as to weight, body mass index (BMI), pre- and
      postoperative diabetes, hypertension, and other comorbidities, including sleep
      apnea, hypoventilation, gastroesophageal reflux, degenerative joint disease,
      urinary incontinence, venous stasis, and pseudotumor cerebri. RESULTS: Of 1,025
      patients treated, 15% had type 2 diabetes mellitus and 51% had hypertension. Of
      those with diabetes, 75% also had hypertension. There was a progressive increase
      in age between patients who had neither diabetes nor hypertension, either
      diabetes or hypertension, or both diabetes and hypertension. At 1 year after GBP
      (91% follow-up), patients lost 66 +/- 18% excess weight (%EWL) or 35 +/- 9% of
      their initial weight (%WL). Hypertension resolved in 69% and diabetes in 83%.
      Patients who resolved their hypertension or diabetes had greater %EWL and %WL
      than those who did not. African-American patients had a higher risk of
      hypertension than whites before GBP and were less likely to correct their
      hypertension after GBP. There was significant resolution of other obesity
      comorbidity problems. At 5 to 7 years after GBP (50% follow-up), %EWL was 59 +/-
      24 and %WL was 31 +/- 13; resolution of hypertension was 66% and diabetes 86%.
      CONCLUSIONS: These data suggest that type 2 diabetes mellitus and hypertension
      may be indirectly related to each other through the effects of obesity, but not
      directly as to cause and effect. The longer a person remains severely obese, the
      more likely he or she is to develop diabetes, hypertension, or both. GBP-induced
      weight loss is effective in correcting diabetes, hypertension, and other
      comorbidities but is related to the %EWL achieved. Severely obese African
      Americans were more likely to have hypertension and respond less well to GBP
      surgery than whites. These data suggest that GBP surgery for severe obesity
      should be provided earlier to patients to prevent the development of diabetes and
      hypertension and their complications.

PMID- 12796571
TI  - Evolution of staged versus primary closure of gastroschisis.
AB  - OBJECTIVE: Since the introduction of a preformed silo to the authors' practice in
      1997, there has been a decrease in primary closure of gastroschisis. To clarify
      the impact of this change, the authors reviewed their results over the past 10
      years. METHODS: From patient records, the authors abstracted the closure method,
      mechanical ventilation days, time to full feeds, mechanical and infectious
      complications, and length of stay. The authors compared groups using the Student
      t test and the Mann-Whitney test, as appropriate. RESULTS: Between 1993 and the
      present, 124 patients were identified. Between 1993 and 1997, 38 children
      presented with gastroschisis. Thirty-two (84.2%) closures were primary and six
      (18.8%) were staged. After 1997, the authors treated 80 children with
      gastroschisis. There were 27 (33.8%) primary and 53 (66.2%) staged closures. Six
      patients with other lethal anomalies were excluded. Length of stay and ventilator
      days were higher for the staged closure group, but infection and mechanical
      complications were less common in the staged closure group. The time to full
      feeds did not differ. CONCLUSIONS: A lower incidence of infection and
      complications related to abdominal compartment syndrome has made staged closure
      of gastroschisis more common in the authors' practice. While it has resulted in a
      longer hospital stay, staged closure decreases the risk of long-term bowel
      dysfunction and need for reoperation.

PMID- 12796572
TI  - Expanded application of extracorporeal membrane oxygenation in a pediatric
      surgery practice.
AB  - OBJECTIVE: To examine the breadth of application and resulting outcomes in a
      university-based extracorporeal membrane oxygenation (ECMO) program directed by
      pediatric surgeons. SUMMARY BACKGROUND DATA: Several randomized control trials
      have supported the use of ECMO in neonates with respiratory failure. No
      comparable data exist for older children and young adults who may be afflicted
      with a variety of uncommon conditions. The indications for ECMO in these patients
      remain controversial. METHODS: Patient data were recorded prospectively and
      reported to the Extracorporeal Life Support Organization. These data were
      analyzed by indications and outcomes on all patients treated since the inception
      of the program. RESULTS: Two hundred sixteen patients were treated with 225
      courses of ECMO. Neonates (188 [87%]) outnumbered 28 older patients (aged 6 weeks
      to 22 years). Overall, 174 patients survived (81%). Sixty-four of 65 (98.5%)
      neonates with meconium aspiration syndrome survived. ECMO support after heart
      (3), lung (2), heart-lung (1), and liver (1) transplant yielded a 57% survival to
      discharge. ECMO also resulted in survival of patients with uncommon conditions,
      including severe asthma (1), hydrocarbon aspiration (1/2), congestive heart
      failure due to a cerebral arteriovenous malformation (1), tracheal occlusion
      incurred during endoscopic stent manipulation (2), meningitis (1), and viral
      pneumonia (3/5). CONCLUSIONS: ECMO can potentially eliminate mortality for
      meconium aspiration syndrome. Survival for other causes of respiratory failure in
      neonates and older children, while not as dramatic, still surpasses that
      anticipated with conventional therapy. Moreover, survival of transplant patients
      has been comparable to that achieved in other children.

PMID- 12796573
TI  - Pediatric trauma is very much a surgical disease.
AB  - OBJECTIVE: The evolution of nonoperative management of certain solid visceral
      injuries has stimulated speculation that management of the severely injured child
      is no longer a surgical exercise. The authors hypothesized that the incidence of
      injuries that require surgical evaluation is disproportionately high in children
      at risk of death or disability from significant injury. METHODS: National
      Pediatric Trauma Registry data were queried for all patients with ICDA-9-CM
      diagnoses requiring at least surgical evaluation. Selected diagnoses included
      CNS: 800 to 804, 850 to 854; thoracoabdominal: 860 to 870; pelvic fracture: 808;
      and acute vascular disruption: 900 to 904. Operative intervention was identified
      by ICDA-9-CM operative codes less than 60 and selected operative orthopedic codes
      between 79.8 and 84.4. At-risk patients were identified as those with at least
      one of the following: Glasgow Coma Scale score less than 15, Glasgow Coma Scale
      motor score less than 6, initial systolic blood pressure less than 90, or Injury
      Severity Scale score more than 10. The incidence of a surgical diagnosis in at
      risk children was compared to the incidence in the population with no
      identifiable risk. Within the population undergoing surgical evaluation, resource
      utilization, as reflected by operative intervention and ICU days, and outcome, as
      reflected by mortality, were compared between the at-risk group and the group
      with no identifiable risk. RESULTS: From 1987 to 2000, 87,424 records were
      complete enough for analysis. Of those, 48,687 (55.6%) patients sustained at
      least one injury requiring a surgical evaluation and 28,645 (32.7%) children were
      determined to be at risk. Mortality for at-risk children was 5.8% versus 0.02%
      for those with no identifiable risk. Of the children at risk, 24,706 (86.2%) had
      at least one injury requiring a surgical evaluation. Of the 58,779 children with
      no risk, 23,981 (40.8%) also had at least one injury requiring a surgical
      evaluation. Operative intervention for surgical injuries was required in 20.5% of
      cases (n = 10,015). Of these, 5,562 (56%) were at-risk children, and they had a
      mortality rate of 11.5%. Of the children not at risk, 4,453 required operative
      care, and they had a mortality of 0.1%. At-risk children undergoing surgery
      required an average of 5.02 days of ICU care compared to 1.2 for cases performed
      on children without risk. CONCLUSIONS: These data clearly demonstrate the primacy
      of surgical pathology as the major determinant of outcome in pediatric injury.
      Operative intervention and the option of timely operative care remain major
      components of clinical management of children with injuries that pose a
      significant risk of morbidity or mortality.

PMID- 12796574
TI  - Adjuvant hepatic arterial chemotherapy following metastasectomy in patients with
      isolated liver metastases.
AB  - OBJECTIVE: To examine survival and toxicity by querying a single-institutional
      experience with adjuvant hepatic arterial infusional (HAI) chemotherapy. SUMMARY
      BACKGROUND DATA: Three randomized series in the literature have examined adjuvant
      HAI after complete resection of liver metastases. Only one of these trials showed
      an overall survival benefit at 2 years but not over the entire time period of the
      study. Previous studies in patients with unresectable disease were plagued by
      high rates of biliary toxicity. METHODS: A retrospective review of a
      prospectively maintained database was performed. Hepatic arterial pumps were
      placed in the standard fashion. Patients received floxuridine at doses previously
      demonstrated as safe in the literature. Standard statistical methods were used.
      RESULTS: Twenty-one of 92 patients underwent placement of hepatic arterial pumps
      at the time of liver resection. The HAI group was similar in all demographic
      measures to the non-HAI group, with the exception that the HAI patients were
      significantly younger. No differences were seen between the groups in either
      disease-free or overall survival, although a trend toward improved hepatic
      progression-free survival was noted. Significant biliary sclerosis developed in
      six patients in the HAI group, requiring chronic indwelling stents in four
      patients. One patient died of progressive liver failure associated with this
      toxicity. CONCLUSIONS: Biliary toxicity is an important potential side effect of
      hepatic arterial chemotherapy. Although larger randomized studies and this one
      suggest significant improvements in hepatic recurrences, these have not reliably
      translated into overall survival benefit. This fact, in light of the potential
      toxicity, would argue for a larger confirmatory trial of HAI in the adjuvant
      setting, incorporating recent advances in systemic therapy and careful attention
      to hepatotoxicity.

PMID- 12796575
TI  - Development of a novel in vitro human tissue-based angiogenesis assay to evaluate
      the effect of antiangiogenic drugs.
AB  - OBJECTIVE: To describe a novel in vitro human tissue-based angiogenic model that
      can predict an individual tumor's response to antiangiogenic drugs. SUMMARY
      BACKGROUND DATA: A number of in vitro and in vivo angiogenesis assays exist, but
      they do not provide potentially useful information for the treatment of an
      individual patient. Clonogenic assays have been used to evaluate the response of
      an individual's tumor to antineoplastic agents, but these tumor fragments are
      cultured in an environment that does not lead to neovessel growth. The authors
      have previously demonstrated that human vein disks or human tumor xenograft
      fragments incorporated into a 0.3% fibrin-thrombin clot will develop angiogenic
      vessel growth from the cut edge of the vessel disk or xenograft fragment.
      METHODS: Fresh human tumor or normal tissue disks (2 x 1 mm) from fresh surgical
      specimens were incorporated into fibrin-thrombin clots overlain with nutrient
      medium containing either 20% fetal bovine serum alone or in combination with
      Epothilone B, a tubulin inhibitor with antiangiogenic properties. Tissue disks
      were visually assessed over time to determine the percentage of wells that
      developed an angiogenic response. Neovessel growth, density, and length were
      graded at intervals using a semiquantitative visual neovessel growth-rating
      scheme (angiogenic index, 0-16 scale) devised in the authors' laboratory.
      RESULTS: Epothilone B treatment at doses of 10-6 mol/L and 10-8 mol/L decreased
      the number of wells that developed an invasive angiogenic response and limited
      the development of vessels that invaded the matrix. At these doses, Epothilone B
      also caused regression of vessels in wells that had been allowed to develop an
      angiogenic response. Treatment of tumors or normal tissues with Epothilone B at
      doses less than 10-8 mol/L was ineffective. CONCLUSIONS: Epothilone B may be an
      effective antiangiogenic agent in a variety of tumor types. The authors speculate
      that this in vitro model might provide useful information to the clinician on the
      effect of specific antiangiogenic agents on individual tumors. This may be
      particularly useful in patients with tumors that, as a group, are unresponsive to
      treatment with antineoplastic agents.

PMID- 12796576
TI  - Improved net protein balance, lean mass, and gene expression changes with
      oxandrolone treatment in the severely burned.
AB  - OBJECTIVE: To determine the effects of the anabolic agent oxandrolone on muscle
      protein and gene expression in severely burned children. SUMMARY BACKGROUND DATA:
      The authors previously showed that oxandrolone increased net muscle protein
      synthesis in emaciated burned patients receiving delayed treatment for severe
      burns. They hypothesized that similar effects would be seen in those treated
      early after burn. METHODS: Thirty-two severely burned children were enrolled in a
      prospective randomized trial. Subjects underwent studies to assess leg protein
      net balance 5 days after the first excision and grafting procedure. Immediately
      after these studies, treatment with placebo (n = 18) or 0.1 mg/kg oxandrolone (n
      = 14) twice a day was started. One week after this, another net balance study was
      performed in each subject. Body weights and total body potassium counting were
      used to determine body compositional changes. Muscle biopsies were taken 1 week
      after treatment in oxandrolone subjects to examine gene expression changes with
      gene array (12,600 genes). RESULTS: Protein net balance did not change in the
      placebo group, while oxandrolone-treated subjects had a significant improvement.
      Body weights and fat free mass significantly decreased in the placebo group,
      while no changes were found in the oxandrolone-treated subjects. Expression
      changes were seen in 14 genes in the oxandrolone group compared to placebo. Some
      of these included myosin light chain (+2.7-fold change), tubulin (+2.3),
      calmodulin (-2.3), and protein phosphatase I inhibitor (-2.8). CONCLUSIONS:
      Oxandrolone improves protein net balance and lean mass in the severely burned.
      These changes are associated with increased gene expression for functional muscle
      proteins.

PMID- 12796577
TI  - The LEGS score: a proposed grading system to direct treatment of chronic lower
      extremity ischemia.
AB  - OBJECTIVE: To prospectively compare the Lower Extremity Grading System (LEGS)
      derived "recommended treatment" to the actual treatment performed and to analyze
      LEGS intergrader scoring consistency by comparing blinded scoring results between
      physician graders. SUMMARY BACKGROUND DATA: Due to technical advances and the
      increased medical complexity of the aging population, the most appropriate
      treatment for chronic lower extremity ischemia-open surgery versus endovascular
      is again in flux. In an attempt to standardize management, the LEGS score, based
      on the best available outcomes data, was devised by the physicians of an
      established vascular service. METHODS: From March to June 2002, all chronically
      ischemic lower extremities that met standard indications for revascularization
      were prospectively enrolled and independently graded with the LEGS score by an
      "endovascular surgeon" and an "open surgeon" for comparative analysis. The
      results were then blindly evaluated to determine whether the LEGS-derived
      "recommended treatment" agreed with the actual treatment rendered and to assess
      for intergrader consistency. Agreement was assessed using kappa statistical
      analysis. RESULTS: Of the 137 presenting limbs (mean patient age 66.4 yo; 43%
      claudication, 57% limb-threatening ischemia), 107 were treated (65% endovascular,
      30% open surgery, 5% amputation), 16 were pending treatment, and 14 were not
      treated because of patient refusal (n = 13) or death (n = 1). The LEGS score
      predicted the actual or offered clinical treatment in 90% of cases. The LEGS
      score comparison between physician graders resulted in identical "recommended
      treatment" in 116 of 128 cases for a 90.6% agreement. CONCLUSIONS: A reproducible
      scoring system to guide the treatment of patients with chronic lower extremity
      ischemia is possible. While systems like the LEGS score may have potential
      clinical application, their use as a treatment standardization tool for future
      prospective outcomes comparisons between open and endovascular surgery will be
      essential.

PMID- 12796578
TI  - Post-shunt resource consumption favors small-diameter prosthetic H-graft
      portacaval shunt over TIPS for patients with poor hepatic reserve.
AB  - OBJECTIVE: To define the role of surgical shunting for patients with poor hepatic
      reserve (Child's class C) in the era of TIPS. SUMMARY BACKGROUND DATA: Most
      physicians prefer TIPS to surgical shunting for patients with poor hepatic
      reserve because of anticipated poor long-term survival. METHODS: Sixty-two
      patients of Child's class C with bleeding varices not amenable to endoscopic
      sclerotherapy or banding were prospectively randomized to undergo TIPS or 8-mm
      prosthetic H-graft portacaval shunt (HGPCS) from 1993 to 1999. Resource
      consumption and survival after shunting were determined. RESULTS: Twenty-nine
      patients underwent TIPS and 33 underwent HGPCS. After HGPCS, survival at 3 years
      was favorable but not statistically superior. TIPS was more often associated with
      shunt stenoses/occlusions, recurrent hemorrhage, shunt revisions, and shunt
      failure. Long-term follow-up documented that after HGPCS, patients required fewer
      hospital and ICU days and fewer units of RBCs transfused. After HGPCS, cost of
      care was less, as was the median cost of care per day of survival. CONCLUSIONS:
      For Child's class C patients undergoing HGPCS or TIPS, long-term survival is
      similar, though favoring HGPCS. Similarly, measures of resource consumption and
      cost of care following hospital discharge favor HGPCS. HGPCS should be
      preferentially applied for acceptable patients without access to convenient
      capable post-shunt care or without definitive plans for imminent transplantation.

PMID- 12796579
TI  - Biologic predictors of survival in node-negative gastric cancer.
AB  - OBJECTIVE: To evaluate factors predictive of survival following curative
      resection for node-negative gastric adenocarcinoma. SUMMARY BACKGROUND DATA:
      Presence or absence of lymph node metastases is the most powerful predictor of
      survival following curative resection for gastric adenocarcinoma. Factors
      predictive of survival in node-negative gastric cancer have not been clarified.
      METHODS: Histopathology and clinical outcome for all patients undergoing R0
      resections for gastric adenocarcinoma at a tertiary center between 1985 and 2001
      were reviewed. RESULTS: Of 1,256 R0 resections performed, 507 (40%) were node
      negative, 465 were T1-T3, and 317 of these were adequately staged, as defined by
      histologic evaluation of at least 15 lymph nodes. Median age was 67 years, and
      62% were male. Forty percent had T1 tumors, 34% were T2, and 26% were T3. Median
      tumor size was 3 cm. Vascular invasion (VI) was present in 17% of tumors and
      neural invasion (NI) in 31%. Extended (D2) lymphadenectomy was performed in 75%
      of cases. Five- and 10-year disease-specific survival rates were 79% and 67%
      respectively. Factors associated with poorer disease-specific survival on
      univariate analysis were male gender, serosal invasion, presence of VI, presence
      of NI, and resection other than distal subtotal gastrectomy. On multivariate
      analysis, NI was not an independent predictor of survival, but correlated
      directly with advancing T stage and tumor size. CONCLUSIONS: Serosal invasion and
      presence of VI are strong predictors of poor survival in this disease. NI
      correlates with T stage and tumor size and may serve as a marker of advanced
      disease.

PMID- 12796580
TI  - Effect of lymphatic mapping on diagnosis and treatment of patients with T1a, T1b
      favorable breast cancer.
AB  - OBJECTIVE: To investigate the incidence of nodal metastasis in a consecutive
      series of patients treated at the authors' institution with highly selective
      criteria, and to determine the impact that lymphatic mapping and sentinel node
      biopsy have on the detection of nodal metastases in this carefully selected
      patient population. METHODS: Study patients were selected from the 7,750 breast
      cancer patients entered into the authors' database from April 1989 to August
      2001, based on the following criteria: nonpalpable, T1a and T1b, non-high nuclear
      grade tumors, without lymphovascular invasion. RESULTS: Of the 7,750 patients in
      the database 1,327 (17%) were found to have T1a and T1b lesions. Three hundred
      eighty-nine patients were confirmed to meet all four selection criteria. This
      represents 5% (389/7,750) of the authors' breast cancer patients and 29.3%
      (389/1,327) of the authors' T1a/T1b tumors. One hundred sixty patients were
      diagnosed before routine use of lymphatic mapping, and only one patient had a
      positive axillary lymph node. Two hundred twenty-nine patients underwent
      lymphatic mapping and sentinel lymph node biopsy, and 10 had a positive axillary
      lymph node. The difference in proportions of nodal positivity between the mapped
      and unmapped patients was significant. CONCLUSIONS: This study clearly
      demonstrates the ability of lymphatic mapping and a more detailed examination of
      the sentinel node to increase the accuracy of axillary staging. It has been
      argued that this highly selected group of breast cancer patients possessing
      retrospectively identified "favorable" characteristics does not require axillary
      staging. This select population represents only 5% of breast cancer patients in
      this series, and the authors do not believe they can be accurately identified
      preoperatively. Therefore, the authors strongly argue for evaluation of the
      axillary nodal status by lymphatic mapping.

PMID- 12796581
TI  - Surgical adverse events, risk management, and malpractice outcome: morbidity and
      mortality review is not enough.
AB  - OBJECTIVE: To review all admissions (age > 13) to three surgical patient care
      centers at a single academic medical center between January 1, 1995, and December
      6, 1999, for significant surgical adverse events. SUMMARY BACKGROUND DATA: Little
      data exist on the interrelationships between surgical adverse events, risk
      management, malpractice claims, and resulting indemnity payments to plaintiffs.
      The authors hypothesized that examination of this process would identify
      performance improvement opportunities overlooked by standard medical peer review;
      the risk of litigation would be constant across the three homogeneous patient
      care centers; and the risk management process would exceed the performance
      improvement process. METHODS: Data collected included patient demographics (age,
      gender, and employment status), hospital financials (hospital charges, costs, and
      financial class), and outcome. Outcome categories were medical (disability: <1
      month, 1-6 months, permanent/death), legal (no legal action, settlement, summary
      judgment), financial (indemnity payments, legal fees, write-offs), and cause and
      effect analysis. Cause and effect analysis attempts to identify system failures
      contributing to adverse outcomes. This was determined by two independent analysts
      using the 17 Harvard criteria and subdividing these into subsystem causative
      factors. RESULTS: The study group consisted of 130 patients with surgical adverse
      events resulting in total liabilities of $8.2 million US dollars. The incidence
      of adverse events per 1,000 admissions across the three patient care centers was
      similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30
      US dollars, women's health = $90 US dollars, trauma = $520 US dollars). Patient
      demographics were not predictive of high-risk subgroups for adverse events or
      litigation. In terms of medical outcome, 51 patients had permanent disability or
      death, accounting for 98% of the indemnity payments. In terms of legal outcome,
      103 patients received no indemnity payments, 15 patients received indemnity
      payments, four suits remain open, and in eight cases charges were written off
      ($0.121 million US dollars). To date, no cases have been adjudicated in court.
      Cause and effect analysis identified 390 system failures contributing to the
      adverse events (mean 3.0 failures per adverse event); there were 4.7 failures per
      adverse event in the 15 indemnity cases. Five categories of causes accounted for
      75% of the failures (patient management, n = 104; communication, n = 89;
      administration, n = 33; documentation, n = 32; behavior, n = 23). The current
      medical review process would have identified 104 of 390 systems failures (37%).
      CONCLUSIONS: This study demonstrates no rational link between the tort system and
      the reduction of adverse events. Sixty-three percent of contributing causes to
      adverse events were undetected by current medical review processes. Adverse
      events occur at the interface between different systems or disciplines and result
      from multiple failures. Indemnity costs per hospital day vary dramatically by
      patient care center (range $3.60-97.60 US dollars a day). The regionalization of
      healthcare is in jeopardy from the burden of high indemnity payments.

PMID- 12796582
TI  - Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis.
AB  - OBJECTIVE: To compare the presentation and short-term results of
      pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis (LPSP) and
      pancreatic adenocarcinoma (PA) and to provide long-term follow-up on patients
      undergoing resection for LPSP. SUMMARY BACKGROUND DATA: LPSP is a rare form of
      chronic pancreatitis characterized by a mixed inflammatory infiltrate centered
      around pancreatic ducts and ductules, combined with obliterative phlebitis. Its
      presentation may mimic that of PA. METHODS: Among 1,648 patients undergoing
      pancreaticoduodenectomy at the authors' institution from January 1992 to May
      2002, 37 with LPSP were identified. The demographics, clinical features, and
      short- and long-term outcomes of these patients were analyzed. Where applicable,
      comparisons were made to a consecutive group of 45 patients who underwent
      pancreaticoduodenectomy for PA from July 2001 to December 2001. RESULTS: Twenty
      four percent (9/37) of the LPSP patients and none of the PA patients had a
      history of either atopic or autoimmune disease. The LPSP patients had a similar
      clinical presentation to the PA patients, but the LPSP patients were less likely
      to have a discrete pancreatic mass on CT and more likely to have CT findings
      suggesting a diffusely enlarged pancreas. The LPSP patients were also less likely
      to have a discrete pancreatic mass at operation, more likely to have a diffusely
      firm or hard gland, and more likely to have a difficult portal vein/superior
      mesenteric vein dissection when compared to the PA patients. Transfusion
      requirement, operative time, postoperative length of stay, and overall
      complication rate were similar between groups; however, the LPSP patients had a
      greater operative blood loss. The median length of follow-up for LPSP patients
      was 33 months. No patients had recurrent jaundice. One patient with LPSP had
      clinically evident recurrent pancreatitis. Among LPSP patients available for
      current telephone interview, 68% subjectively rated their quality of life as
      better, 18% reported no change, and 14% reported diminished quality of life
      compared to before surgery. CONCLUSION: LPSP mimics PA in clinical presentation,
      though CT findings of a diffusely enlarged pancreas without a discrete mass may
      suggest a diagnosis of LPSP. Nevertheless, differentiation from pancreatic
      neoplasia remains difficult. Patients undergoing pancreaticoduodenectomy for LPSP
      have durable relief of symptoms and a subjectively improved quality of life.

PMID- 12796584
TI  - Fibrin sealant improves hemostasis in peripheral vascular surgery: a randomized
      prospective trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of an investigational fibrin
      sealant (FS) in a randomized prospective, partially blinded, controlled,
      multicenter trial. SUMMARY BACKGROUND DATA: Upper extremity vascular access
      surgery using polytetrafluorethylene (PTFE) graft placement for dialysis was
      chosen as a reproducible, clinically relevant model for evaluating the usefulness
      of FS. The FS consisted of pooled human fibrinogen (60 mg/mL) and thrombin (500
      NIH U/mL). Time to hemostasis was measured, and adverse events were monitored.
      METHODS: Consenting adult patients (n = 48) undergoing placement of a standard
      PTFE graft were randomized in a 2:1:1 ratio to the treatment group using FS (ZLB
      Bioplasma AG, Bern, Switzerland), oxidized regenerated cellulose (Surgicel,
      Johnson & Johnson, New Brunswick, NJ), or pressure. Patients received heparin
      (3,000 IU IVP) before placement of vascular clamps. If the treatment was FS,
      clamps were left in place for 120 seconds after the application of study material
      to permit polymerization. If treatment was Surgicel, clamps were left in place
      until the agent had been applied according to manufacturer's instructions. If the
      treatment was pressure, clamps were released as soon as the investigator was
      ready to apply compression. Immediately after release of the last clamp, the
      arterial and venous suture lines were evaluated for bleeding. The time to
      hemostasis at both the venous and arterial sites was recorded. RESULTS:
      Significant (P < or =.005) reduction in time to hemostasis was achieved in the FS
      group. Thirteen (54.2%) patients randomized to FS experienced immediate
      hemostasis at both suture lines following clamp removal compared to no patients
      using Surgicel or pressure. Only one patient (7.1%) in the Surgicel group and no
      patients in the pressure group experienced hemostasis at 120 seconds from clamp
      removal, compared to 13 (54.2%) patients for FS. Adverse events were comparable
      in all groups. There were no seroconversions. CONCLUSIONS: FS achieved more rapid
      hemostasis than traditional techniques in this peripheral vascular procedure. FS
      use appeared to be safe for this procedure.

PMID- 12796585
TI  - Complex blunt aortic injury or repair: beneficial effects of cardiopulmonary
      bypass use.
AB  - OBJECTIVE: To compare the outcomes and associated morbidity in patients with
      blunt aortic injury (BAI) repaired using cardiopulmonary bypass versus no bypass.
      Special consideration is given to the influence of bypass in the outcome of
      complex injuries or repair circumstances. SUMMARY BACKGROUND DATA: There are
      conflicting data concerning the utility of bypass techniques in the operative
      management of BAI, and controversy over the subject persists. During the last
      decade, surgeons at the authors' institution have undergone a change in
      philosophy concerning management of these injuries and began almost exclusively
      using cardiopulmonary bypass for the repair in 1996. This project explores the
      effects of this change in the management of BAI. METHODS: The records of all
      patients with BAI admitted to a level 1 trauma center over a period of 12 years
      were reviewed for demographics, injury characteristics, operative technique, and
      outcome. The bypass group was compared to the no bypass group with respect to
      morbidity and mortality. Those with a complex injury or repair (CI/R) were
      examined as a subgroup. CI/R was defined as the presence of an injury with
      extension proximal to the subclavian artery, involvement of branch vessels, or
      requirement of maneuvers interfering with anastomosis construction, such as
      cardiac massage. RESULTS: From January 1, 1990, to December 31, 2001, 91 patients
      were admitted to Wake Forest University Baptist Medical Center with BAI. Sixty
      five of these underwent operative repair. Sixty (32 no bypass, 28 bypass)
      survived to the immediate postoperative period. Injury Severity Score was similar
      (33 no bypass, 31 bypass, P =.48), as was admission base deficit (-9.2 m Eq/L no
      bypass vs. -7.0 mEq/L B, P =.13). Paraplegia occurred in four (12%) of the no
      bypass group as opposed to 0 of the bypass group (P =.05). No patient in the
      bypass group experienced complications related to heparinization, and two (7%)
      experienced bypass-related complications (cerebral edema, femoral vein
      laceration). Mean clamp time for the entire group was 27 minutes. Examination of
      the 10 patients with CI/R who survived the operating room showed markedly longer
      clamp times (59 minutes vs. 22 minutes, P <.0001) and a higher rate of
      paraplegia/paresis (30% vs. 2%, P =.01) as compared to those without CI/R.
      Logistic regression demonstrated a significant relationship between increasing
      clamp time and the CI/R classification (P =.007). All three (100%) of the CI/R
      patients repaired via clamp-and-sew technique developed paraplegia, while none of
      the seven CI/R patients repaired on bypass developed neurologic changes (P
      =.008). CONCLUSIONS: With the use of cardiopulmonary bypass in the repair of BAI,
      the incidence of paraplegia/paresis has fallen. While patients with typical
      injuries and uncomplicated repair can expect good results with either technique,
      cardiopulmonary bypass provides significant advantages in the repair of those
      with CI/R. With the use of bypass, no CI/R patient developed paraplegia, while
      all CI/R patients experienced paraplegia before bypass use. Although others have
      reported the importance of clamp time, in this series clamp time appeared largely
      to be a surrogate variable for complexity of injury.

PMID- 12796583
TI  - Influence of transfusions on perioperative and long-term outcome in patients
      following hepatic resection for colorectal metastases.
AB  - OBJECTIVE: To determine if transfusion affected perioperative and long-term
      outcome in patients undergoing liver resection for metastatic colorectal cancer.
      SUMMARY BACKGROUND DATA: Blood transfusion produces host immunosuppression and
      has been postulated to result in adverse outcome for patients undergoing surgical
      resection of malignancies. METHODS: Blood transfusion records and clinical
      outcomes for 1,351 patients undergoing liver resection at a tertiary cancer
      referral center were analyzed. RESULTS: Blood transfusion was associated with
      adverse outcome after liver resection. The greatest effect was in the
      perioperative course, where transfusion was an independent predictor of operative
      mortality, complications, major complications, and length of hospital stay. This
      effect was dose-related. Patients receiving one or two units or more than two
      units had an operative mortality of 2.5% and 11.1%, respectively, compared to
      1.2% for patients not requiring transfusions. Transfusion was also associated
      with adverse long-term survival by univariate analysis, but this factor was not
      significant on multivariate analysis. Even patients receiving only one or two
      units had a more adverse outcome. CONCLUSIONS: Perioperative blood transfusion is
      a risk factor for poor outcome after liver resection. Blood conservation methods
      should be used to avoid transfusion, especially in patents currently requiring
      limited amounts of transfused blood products.

PMID- 12796586
TI  - Prospective randomized trial of carotid endarterectomy with
      polytetrafluoroethylene versus collagen-impregnated dacron (Hemashield) patching:
      late follow-up.
AB  - OBJECTIVE: To compare the late clinical outcome and incidence of recurrent
      stenosis after carotid endarterectomy (CEA) with polytetrafluoroethylene (PTFE)
      versus Hemashield patching. SUMMARY BACKGROUND DATA: Several randomized trials
      have confirmed the advantages of patching over primary closure when performing
      CEA. METHODS: Two hundred CEAs (180 patients) were randomized into 100 with PTFE
      patching and 100 with Hemashield. All patients underwent postoperative color
      duplex ultrasounds at 1, 6, and 12 months, and every year thereafter. The mean
      follow-up was 26 months. Kaplan-Meier analysis was used to estimate the risk of
      re-stenosis, stroke, and stroke-free survival. A multivariate analysis of various
      risk factors was also done. RESULTS: Demographic and clinical characteristics
      were similar in both groups. The incidence of all ipsilateral strokes (early and
      late) was 8% (7% perioperative) for Hemashield versus 0% for PTFE patching. Both
      groups had similar mortality rates. The cumulative stroke-free rates at 6, 12,
      24, and 36 months were 93%, 93%, 93%, and 89% for Hemashield versus 100%, 100%,
      100%, and 100% for PTFE patching. The cumulative stroke-free survival rates at 6,
      12, 24, and 36 months were 90%, 89%, 87%, and 79% for Hemashield versus 98%, 98%,
      92%, and 92% for PTFE patching. Kaplan-Meier analysis also showed that freedom
      from 50% or greater re-stenosis at 6, 12, 24, and 36 months was 89%, 81%, 73%,
      and 66% for Hemashield versus 100%, 100%, 100%, and 92% for PTFE. Similarly, the
      freedom from 70% or greater re-stenosis at 6, 12, 24, and 36 months was 93%, 91%,
      86%, and 78% for Hemashield versus 100%, 100%, 100%, and 100% for PTFE.
      Univariate and multivariate analyses of demographic and preoperative risk factors
      showed that only Hemashield was significantly associated with a higher incidence
      of 70% or greater recurrent stenosis. CONCLUSIONS: PTFE patching was superior to
      Hemashield in lowering the incidence of postoperative ipsilateral strokes and
      late recurrent stenosis.

PMID- 12796587
TI  - Influence of celiac axis lymph nodes in the definitive treatment of esophageal
      cancer.
AB  - The management of patients with cancer of the distal thoracic esophagus is often
      made difficult by the presence of disease in the celiac axis lymph nodes. We
      investigated the outcome of such patients treated for cure in an attempt to
      better define the best treatment. The charts of all patients with esophageal
      cancer treated at the Department of Radiation Oncology at the Medical University
      of South Carolina between 1990 and 1998 were reviewed. Three groups of patients
      were analyzed: NoMo, N1Mo, and patients with positive celiac axis lymph nodes
      (M1a). Among 217 patients, 56 patients received radiotherapy with intent to cure,
      along with surgery, chemotherapy, or some combination of these modalities. Of
      these, 14 had disease of the distal esophagus with the celiac axis as their only
      site of distant disease. Comparison of survival curves in the three analyzed
      groups revealed no statistically significant differences in terms of overall
      survival (p = 0.3458 by the log-rank test) or disease-free survival (p = 0.5509
      by the log-rank test). Patients with positive celiac axis lymph nodes as their
      only site of "M1" disease experienced a 2-year survival rate similar to "Mo"
      patients when treated with curative intent.

PMID- 12796588
TI  - Prognostic assessment of gastrointestinal stromal tumor.
AB  - The term "gastrointestinal stromal tumor" (GIST) has been applied to a collection
      of distinctive mesenchymal tumors occurring within the human gastrointestinal
      tract. As new drug therapy becomes available, data regarding the natural history
      of these unusual tumors are necessary to provide selection factors for treatment.
      Ninety-eight patients had light microscopy compatible with GIST at a single
      institution from 1989 to 2000. After immunostaining with c-kit and
      histopathologic review, 69 were judged to be GIST. All prognostic indicators were
      determined for gastric GIST, intestinal GIST, and all locations combined. The
      location of the GIST did not have a significant impact on survival. Clinically,
      tumor size, peritoneal cancer index, and completeness of cytoreduction had a
      significant impact on prognosis for GIST at all locations. Pathologically,
      cytologic atypia, necrosis, invasion and number of mitoses were significant
      prognostic indicators for GIST. Criteria to separate three pathologic groups of
      GIST according to the tumor size and the mitotic count were useful to evaluate
      the tumor behavior; in the borderline pathologic group invasion and cytologic
      atypia were statistically significant prognostic criteria. The cell phenotypes,
      as determined by immunostains, correlated with the prognosis of gastric GIST but
      not intestinal GIST. A correlation between the immunostain Ki-67 but not CD-34 or
      desmin and the prognosis was observed. It is possible to select clinical and
      pathologic parameters of GIST that impact on prognosis. Invasion and necrosis
      help to determine the prognosis with borderline tumors. The immunostain Ki-67
      correlated with the prognosis and may be helpful to assess prognosis when dealing
      with small biopsy specimens.

PMID- 12796589
TI  - Arm edema after lumpectomy and breast irradiation.
AB  - Ipsilateral arm edema can be a troublesome adverse sequel of breast conservation
      therapy. We carried out a prospective study of arm edema in every patient (265)
      seen during a 6-month period for follow-up after radiotherapy postlumpectomy for
      unilateral primary breast cancer. One hundred eighty-one (181) women (68.3%) had
      an axillary dissection. All had radiotherapy to the breast via parallel opposed
      tangential beams. Only eight (3%) had additional separate portals for irradiation
      of nodal areas. Adjuvant systemic therapy consisted of tamoxifen alone in 127
      patients (47.9%) and chemotherapy with or without tamoxifen in 60 (22.6%).
      Ipsilateral arm edema developed in 19 patients (7.2%). Edema was mild (1+) in 16
      patients, and moderate in 3 (2+). Multivariate analysis revealed that the risk of
      arm edema was significantly increased in heavier women (p = 0.0016), women who
      had an axillary dissection (p = 0.0446), and women who received tamoxifen (p =
      0.0385).

PMID- 12796590
TI  - Nonpalpable thyroid carcinoma: clinical controversies on preoperative selection.
AB  - This article emphasizes some controversies concerning the preoperative selection
      of nonpalpable thyroid tumors. The prevalence of occult thyroid carcinoma in
      surgical series (1.8-10%) is not higher than in autopsy thyroid series (2.7-24%).
      The prevalence of occult thyroid carcinoma in thyroid glands examined in the same
      institution by ultrasound, for a clinical thyroid abnormality or for
      investigation of other neck structures without clinically evident or suspected
      thyroid disease, varies from 3% to 8% and is very similar independent of the fact
      that a thyroid abnormality is or is not the indication for ultrasonography. These
      data suggest that the presence of a thyroid disease is not a risk factor for
      harboring an occult thyroid carcinoma (except for C-cell hyperplasia in the rare
      case of MEN 2 syndromes). As it is not cost effective to examine all the
      nonpalpable lesions with fine-needle aspiration (FNA) guided by ultrasounds, it
      is necessary to define to which extent ultrasound is useful in selecting those
      lesions to be examined cytologically by FNA. The use of ultrasound to select
      these lesions is very controversial. Ultrasound-guided cytologic diagnosis of
      nonpalpable nodules is not as accurate as in the case of palpable nodules.
      Sampling of material adequate for cytologic analysis depends on the lesion size;
      it is 64% for a 0.7-cm lesion and it increases to 86.7% for a mean size of 1.1
      cm. For the diagnosis of occult thyroid carcinomas (< or =1 cm), sensitivity is
      35.8% and false-negative results are 49.3%. Nonpalpable nodules with a size of
      1.5 cm represent an absolute indication to perform an ultrasound-guided FNA
      because this is the size limit for dividing thyroid nodules in probably innocuous
      or potentially dangerous categories and because the cytologic diagnosis of
      nodules of this size is sufficiently reliable. For the smaller incidentally
      discovered thyroid nodules following ultrasound, physicians should discuss with
      the patient whether and when to perform an ultrasound-guided FNA considering the
      patient's data (risk factors, age, health state, etc.), the natural history of a
      small thyroid carcinoma, as well as the accuracy of ultrasound and ultrasound
      guided FNA in the specific institution.

PMID- 12796591
TI  - Randomized phase II study of daily versus continuous-infusion schedules of
      topotecan in the treatment of extensive-stage small cell lung cancers.
AB  - A randomized two-stage, phase II study was conducted to assess the antitumor
      activity of two different schedules of topotecan in the treatment of extensive
      stage small-cell lung cancer (SCLC) in chemotherapy-naive patients. A total of 40
      eligible patients were randomized to receive either the daily schedule, with
      topotecan being administered intravenously at 1.5 mg/m2 daily for 5 days every 3
      weeks, or the continuous-infusion schedule, with topotecan administered
      intravenously at a dosage of 1.3 mg/m2 per day over 72 hours every 4 weeks.
      Randomization to the continuous-infusion schedule was discontinued due to
      inactivity, and an additional 20 patients were treated on the daily schedule.
      Patients received an average of 5 courses (range: 1-13) of the daily schedule
      compared to an average of 2 courses (range: 1-7) of the continuous-infusion
      schedule (p < 0.01). Confirmed response rates for the daily and continuous
      infusion schedules are 62.5% (90% CI: 49-75%) and 15% (90% CI: 1-29%),
      respectively. Toxicity was predominantly hematologic with 92% (55/60) having
      greater than or equal to grade III neutropenia and 58% (35/60) reporting greater
      than or equal to grade III leukopenia for both IV schedules. Nonhematologic
      toxicity was very mild, with only 10% (6/60) patients experiencing grade IV
      toxicities. One patient died of infection on the continuous-infusion arm. Median
      times to progression for the daily and continuous-infusion schedules are 5 months
      (90% CI: 4.4-7.2) and 2 months (90% CI: 1.1-2.1), respectively. Estimated 1-year
      survival rates for patients receiving daily and continuous-infusion schedules are
      63% (90% CI: 51-76%) and 55% (90% CI: 39-77%), respectively. Fifty percent
      (30/60) of patients received second-line therapy with etoposide and cisplatin.
      Forty-three percent (13/30) of patients who received second-line therapy achieved
      a confirmed response. Topotecan showed significant activity in the treatment of
      extensive stage SCLC when administered as a brief daily IV repeated every 3
      weeks.

PMID- 12796592
TI  - Electron arc irradiation of the postmastectomy chest wall in locally recurrent
      and metastatic breast cancer.
AB  - The purpose of this study was to evaluate local-regional control and overall
      survival in women with locally recurrent and metastatic breast cancer (MBC)
      treated with postmastectomy electron arc therapy. Postmastectomy electron arc
      irradiation was used to treat 39 women with isolated local-regional recurrence of
      breast cancer following mastectomy, and 14 patients with MBC who had, or who were
      at high risk of, local-regional recurrence. After computed tomography treatment
      planning, patients were treated with electron arc radiotherapy to a median dose
      of 59.3 Gy. The median follow-up for alive patients was 45.4 months. For patients
      with local-regional recurrence, the 5-year local-regional control and overall
      survival rates were 74% and 43%, respectively. The 2-year overall survival was
      greater for those patients with a disease-free interval greater than 24 months
      when compared to patients with a disease-free interval less than 24 months (83%
      vs. 60%, respectively); however, the median survival was not significantly
      different (57.6 and 58.6 months, respectively). Patients with a solitary nodule
      at recurrence had an improved 5-year overall survival of 58% compared with 40%
      for patients with multiple lesions. For patients with metastatic disease, the 5
      year local-regional control and overall survival rates were 76% and 31%,
      respectively. Local-regional control can be achieved in the majority of patients
      with local-regionally recurrent breast cancer (74%) or MBC (76%) who had, or who
      were, at high risk of local-regional recurrence treated with postmastectomy
      electron arc irradiation.

PMID- 12796593
TI  - Gemcitabine-induced peripheral edema: report on 15 cases and review of the
      literature.
AB  - Some degree of peripheral edema occurs in up to 20% of patients treated with
      gemcitabine (Gemzar). The edema is typically mild, requiring discontinuation of
      the drug in less than 1% of patients. Most patients require no therapy. However,
      in cases of peripheral edema, grade II or higher, suspension of gemcitabine and
      treatment with corticosteroids are often necessary, and permanent discontinuation
      of gemcitabine may be required on occasion. We have identified 15 cases of
      peripheral edema, grade II or greater, developing in patients receiving
      gemcitabine chemotherapy at Memorial Sloan-Kettering Cancer Center. The diagnosis
      was made based on temporal association with drug administration, and exclusion of
      other potential acute causes of edema including progression of disease and deep
      vein thrombosis. The 15 patients in this series represent less than 1% of all
      patients treated with gemcitabine at this institution over the same time period.
      Gemcitabine was immediately discontinued at the time of the onset of edema in 7
      of the 15 patients due to severity of the symptoms. Thirteen of the 15 patients
      in this case series had experienced peripheral edema previously, and 6 had active
      low-grade edema at the time the gemcitabine was first administered. Patients
      receiving gemcitabine should be advised of this potential complication and urged
      to promptly report its development so that comorbid conditions can be excluded
      and proper supportive measures initiated. Patients predisposed to peripheral
      edema from some other cause may be at increased risk for developing severe
      peripheral edema with gemcitabine.

PMID- 12796594
TI  - Radiotherapy for symptomatic metastases to the mandible in adults.
AB  - Since 1996, seven patients from six radiotherapy facilities that treat more than
      2,000 patients per year were treated with radiotherapy for symptomatic metastases
      to the mandible from primary carcinoma of the prostate (3 patients), carcinoma of
      the breast (2 patients), adenocarcinoma of the ethmoid sinuses (1 patient), and
      multiple myeloma (1 patient). All patients presented with pain of several weeks'
      duration and had radiographic confirmation of a destructive lesion in the
      mandible. Administered radiotherapy doses ranged from 400 cGy/1 fraction to 4,000
      cGy/20 fractions. All patients experienced excellent palliation with complete or
      almost complete resolution of all symptoms within 1 month. The authors suggest
      short courses of radiotherapy for symptomatic metastases to the mandible.

PMID- 12796595
TI  - Bimonthly leucovorin, infusion 5-fluorouracil, hydroxyurea, and irinotecan
      (FOLFIRI-2) for pretreated metastatic colorectal cancer.
AB  - Irinotecan has shown activity in advanced colorectal cancer resistant to
      leucovorin and fluorouracil. Preclinical experiments on cell cultures and human
      tumor xenografts indicated potential synergy when combining irinotecan and
      fluorouracil. We designed a new regimen combining leucovorin, fluorouracil,
      irinotecan, and hydroxyurea (FOLFIRI-2) and conducted a phase II study to
      establish its efficacy and tolerance in advanced colorectal cancer refractory to
      fluorouracil and oxaliplatin. Treatment was repeated every 2 weeks and consisted
      of leucovorin 400 mg/m2 on day 1, immediately followed by 46 hours of continuous
      infusion of fluorouracil 2,000 mg/m2, irinotecan 180 mg/m2 on day 3, and
      hydroxyurea 1,500 mg the day before leucovorin, and on days 1 and 2. Treatment
      was continued until progression or limiting toxicity. Twenty-nine heavily
      pretreated patients entered the study. Five patients achieved an objective
      response (17%), and 12 obtained stabilization of disease or minor response (52%).
      Five patients failed to continue treatment (17%) because of toxicity or worsening
      condition. From the start of FOLFIRI-2 treatment, median progression-free
      survival was 4.1 months and median survival was 9.7 months. Grade III/IV National
      Cancer Institute-Common Toxicity Criteria toxicities were nausea 17%, diarrhea
      31%, mucositis 14%, neutropenia 52%, and febrile neutropenia 14%. FOLFIRI-2
      achieved a good rate of response and stabilization in heavily pretreated patients
      despite significant toxicity.

PMID- 12796596
TI  - Oncogenes in male breast cancer.
AB  - The objective of this study was to assess the degree of expression and prognostic
      significance of c-erbB-2, p53, and bcl-2 in male breast cancer (MBC). Thirty male
      patients with the diagnosis of adenocarcinoma of the breast were studied
      retrospectively. All patients underwent surgery; c-erbB-2, p53, and bcl-2 were
      immunohistochemically stained on sections from formalin-fixed, paraffin-embedded
      tissues. Seventeen (56.7%) of the 30 cases of MBC were bcl-2 positive. Few
      specimens were found positive for c-erbB-2 (6.7%) and p53 (6.7%). The 5-year
      survival rate was marginally better for those patients with tumors staining
      positively for bcl-2 (p = 0.05). It was impossible to estimate the association
      between survival rate and p53 and c-erbB-2 expression because of the small number
      of positively stained specimens. In this study, only bcl-2 showed marginal
      association to other tumor parameters and a trend toward a better 5-year survival
      rate. At present there is inadequate evidence to support the use of molecular
      markers as independent prognostic markers in MBC.

PMID- 12796597
TI  - Interferon-alpha-induced focal segmental glomerulosclerosis in chronic
      myelogenous leukemia: a case report and review of the literature.
AB  - Chronic myelogenous leukemia (CML), hepatitis C, and interferon alpha (IFNalpha)
      have all been associated with renal dysfunction. In this paper we present a
      patient with the diagnosis of nephrotic syndrome and a known history of hepatitis
      C who received IFNalpha therapy for newly diagnosed CML. The renal biopsy showed
      focal segmental glomerulosclerosis, which has only been previously reported in
      two cases of CML treated with IFNalpha. There have also been two cases of
      patients with hepatitis C associated with focal segmental glomerulosclerosis.
      Despite the underlying hepatitis C, this case represents renal abnormalities
      consistent with IFNalpha therapy for CML.

PMID- 12796598
TI  - Induction chemotherapy with carboplatin/paclitaxel followed by surgery or
      standard radiotherapy and concurrent daily low-dose cisplatin for locally
      advanced non-small cell lung cancer (NSCLC).
AB  - Five-year survival in patients with unresectable non-small-cell lung cancer
      (NSCLC) is less than 10%. In the present phase II study, 43 patients with locally
      advanced stage IIIA or selected IIIB NSCLC were given four courses of carboplatin
      AUC = 6 and paclitaxel 200 mg/m2 (3-hour infusion), every 3 weeks. Responsive
      patients, when possible, underwent surgery followed by standard radiotherapy (50
      Gy) or radiotherapy (60 Gy), with concurrent cisplatin as intravenous continuous
      infusion of 4 mg/m2/d. Sixteen of the 42 evaluable patients achieved partial
      response (38%) and 3 complete response (CR) (7%) for an overall response rate of
      45% (95% CI 30.1-60.2). R0 resectability rate was 29%, with 21% of pathologic
      CRs. Three more CRs were achieved with concurrent chemoradiotherapy in responsive
      but unresected patients. Grade III/IV hematologic toxicity was 9%, while one
      perioperative death occurred. The median duration of response was 14 months
      (range: 3-44+); median survival was 15 months (range: 9-47+). One-year and 2-year
      survival rates were 51% and 22%, respectively. The median survival in the
      responsive resected patients was 26 months, with 2-year survival of 57%.
      Carboplatin/paclitaxel represents an effective and well-tolerated induction
      therapy, suggesting its possible role in combination with radiotherapy as
      neoadjuvant treatment in locally advanced NSCLC in alternative to cisplatin-based
      regimens.

PMID- 12796599
TI  - Atypical thymic carcinoid and malignant somatostatinoma in type I multiple
      endocrine neoplasia syndrome: case report.
AB  - Thymic carcinoid and malignant somatostatinoma are both rare, and their
      concurrent presence in multiple endocrine neoplasia type 1 (MEN-1) has never been
      reported in the English literature to date. We present a patient with thymic
      carcinoid and malignant somatostatinoma in association with MEN-1. The patient
      eventually died of pulmonary aspergillosis and respiratory failure. Autopsy
      showed a 16 x 10 x 8-cm thymic carcinoid tumor, parathyroid and adrenal gland
      hyperplasia, and malignant somatostatinoma of the pancreas with a metastatic
      tumor over the splenic hilum.

PMID- 12796600
TI  - Neurocognitive and functional assessment of patients with brain metastases: a
      pilot study.
AB  - The outcome of patients with brain metastases is generally poor. Survival alone
      is not necessarily a good measure of clinical outcome. Measures of neurocognitive
      function and the impact of the disease and treatments on functional status also
      need to be considered. Although these parameters have been measured in patients
      with primary brain tumors, they have not been as thoroughly evaluated in patients
      with brain metastases. The Mini-Mental State Examination provides limited
      assessment of neurocognitive domains impaired in brain tumor patients. It is less
      sensitive to mild impairment, does not avoid memorized learning from repeat
      administration, and does not have validated alternative forms necessary for non
      English speaking patients. To determine the feasibility of using a more
      comprehensive neurocognitive test battery, motor, verbal, executive, and daily
      functions were assessed in 30 patients with brain metastases. The test battery
      included the Hopkins Verbal Learning Tests, Controlled Oral Word Association
      Test, Grooved Pegboard Test, Trailmaking Tests A and B, and the Barthel Index. In
      this study, there was complete patient compliance, with average test completion
      time of 23 +/- 6 minutes. Despite high functional status, most patients
      demonstrated impairment in memory and fine motor domains. Neurocognitive test
      batteries can and should be used in patients with brain metastases enrolled in
      clinical trials.

PMID- 12796601
TI  - Gemcitabine, Paclitaxel, and piritrexim: a phase I study.
AB  - Piritrexim is a new antifolate that has shown activity in methotrexate-resistant
      tumors. Gemcitabine is an antimetabolite similar in structure to cytosine
      arabinoside with early studies demonstrating activity in a variety of cancers. It
      also has apparent synergistic activity with antifolates from initial work in
      tumor models. Paclitaxel is an antimicrotubule agent that has a wide spectrum of
      activity against a variety of solid tumors. The combination of gemcitabine,
      paclitaxel, and piritrexim was assessed in this phase I trial. Thirty patients
      were enrolled. The starting doses were piritrexim 25 mg orally twice daily (days
      1-4, 15-18), paclitaxel 75 mg/m2 (days 1, 15), and gemcitabine 750 mg/m2 (days 1,
      15), which then was escalated in a stepwise fashion. Four patients achieved
      stable disease while on study, whereas one patient with a poorly differentiated
      neuroendocrine tumor achieved a partial response. The main toxicity was
      myelosuppression. The maximum tolerated dose was thought to be piritrexim 25 mg
      orally three times daily (days 1-4), paclitaxel 150 to 175 mg/m2 (days 1, 15),
      and gemcitabine 1,000 mg/m2 (days 1, 15). The combination of these new
      antifolates with paclitaxel and gemcitabine appears safe and should be considered
      for phase II trials in known responsive tumors such as transitional cell
      carcinomas.

PMID- 12796602
TI  - Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile
      neutropenia therapy in high-dose chemotherapy patients.
AB  - An open labeled randomized trial comparing the efficacy and cost of empirically
      applied cefepime (C) as monotherapy versus combination therapy consisting of
      ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in
      febrile neutropenic patients following high-dose chemotherapy (HDC) +/-
      radiation, with or without peripheral blood stem cell support. Over a 28-month
      period, 126 patients were screened and included in the study. Using afebrile
      status following 3 days of therapy as a primary endpoint, both regimens produced
      comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of
      vancomycin for resistant gram-positive infections and alteration of gram-negative
      infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29%
      vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal
      therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between
      the two groups in that the "C" group had a significantly higher number of
      allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A"
      group had a significantly greater number of autologous peripheral blood stem cell
      patients (p < 0.0001). Despite this difference, the C group had a significantly
      lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown
      that C treatment of febrile neutropenic patients following HDC results in similar
      efficacy and lower cost when compared to T/A, despite the inclusion of higher
      risk patients in the C group.

PMID- 12796604
TI  - Squamous cell carcinoma at herniorrhaphy and unilateral renal agenesis.
AB  - Unilateral renal agenesis occurs infrequently. However, it has been associated
      with malignancies at multiple primary sites, anomalies of the genitourinary
      system, and supernumerary limbs. We present the case of a 60-year-old man with an
      incarcerated left inguinal hernia and renal insufficiency. At herniorrhaphy, he
      had squamous cell carcinoma in the hernia sac. A postoperative evaluation
      revealed unilateral renal agenesis, stage IV squamous cell carcinoma of the
      urinary bladder, and urolithiasis. The clinician should consider the
      genitourinary system as a primary site when patients present with the unusual
      finding of squamous cell carcinoma in the abdominal cavity and unilateral renal
      agenesis.

PMID- 12796603
TI  - Cost utility analysis of first-line hormonal therapy in advanced breast cancer:
      comparison of two aromatase inhibitors to tamoxifen.
AB  - Recent randomized clinical trials (RCT) comparing anastrozole (Arimidex) and
      letrozole (Femara) to tamoxifen in the first-line treatment of postmenopausal
      women with advanced hormone-sensitive breast cancer have demonstrated that both
      agents were at least as effective as tamoxifen. In addition, one RCT has revealed
      significant superiority of letrozole to tamoxifen with regard to tumor response
      rate and time to progression. Based on the efficacy and toxicity data,
      anastrozole or letrozole may replace tamoxifen. A cost effectiveness analysis was
      undertaken to determine whether the new agents are economically acceptable
      alternatives to tamoxifen. In the absence of a randomized three-arm trial, a
      decision model was developed to simulate and compare the most common therapeutic
      outcomes. The clinical data were obtained from a meta analysis of modern (i.e.,
      post-1990) randomized trials. Clinical outcomes data from the various trials were
      statistically pooled using a random effects model to provide point estimates and
      95% confidence intervals. Total hospital resource consumption was collected from
      the charts of 87 patients with advanced disease who had failed tamoxifen therapy.
      The model suggested a comparable duration of quality-adjusted progression-free
      survival between letrozole and anastrozole, both being superior to tamoxifen (179
      days vs. 172 days vs. 161 days). Letrozole and anastrozole had overall costs of
      Can2,883 dollars and 2,847 dollars per patient, respectively, which were
      marginally higher than tamoxifen at Can2,258 dollars per patient. When the costs
      and benefits were combined, the data generated an incremental cost per quality
      adjusted progression-free year of 12,500 dollars and 19,600 dollars for letrozole
      and anastrozole, respectively, relative to tamoxifen. Letrozole and anastrozole
      are both economically acceptable alternatives to tamoxifen in the first-line
      treatment setting. However, when efficacy and cost effectiveness are considered
      together, letrozole could be preferentially considered.

PMID- 12796605
TI  - Translocation (11;15;19): a highly specific chromosome rearrangement associated
      with poorly differentiated thymic carcinoma in young patients.
AB  - Thymic carcinoma is a rare epithelial neoplasm of the thymus. The presence of a
      specific chromosomal abnormality may augment diagnosis and therapeutic
      stratification. We report a 15-year-old boy diagnosed with thymic carcinoma who
      presented with a large anterior mediastinal mass, pleural effusion, and bone
      metastasis. The pleural fluid, cytology, bony lesions, and bone marrow were
      examined and chromosomal studies were performed. Histologic and
      immunohistochemical studies confirmed a poorly differentiated squamous cell type
      of thymic carcinoma. The karyotype of the pleural fluid at the time of diagnosis
      revealed a complex three-way translocation t(11;15;19)(p15;q12;p13.3). The
      constitutional karyotype was 46,XY. Five months after diagnosis, a bone marrow
      aspirate demonstrated tetraploidy with all translocation chromosomes in
      duplicate, as well as an unbalanced rearrangement involving chromosome 1:
      92,XXYY,t(11;15;19)(p15;q12;p13.3)x2[15]/92,XXYY,idem,add(1)(qter)[5]. Despite
      aggressive multiagent chemotherapy, the patient's condition progressed with bone
      marrow disease and he died 6 months after diagnosis. Several case reports of a
      similar chromosomal abnormality have been reported for thymic carcinoma in young
      patients with poor outcome. This karyotypic abnormality appears to mark a cohort
      of patients with thymic carcinoma who have a poor prognosis despite aggressive
      chemotherapy.

PMID- 12796606
TI  - Simple staging criteria for esophageal carcinoma: classification with a strict
      prognostic stratification.
AB  - Some staging criteria for carcinoma of the esophagus have been proposed. However,
      none of them satisfied all the appropriateness providing an excellent prognostic
      stratification and simplicity to use. The aim of the current study was to
      establish simple and appropriate criteria to determine the clinical stage with a
      strict prognostic stratification for carcinoma of the esophagus. Two hundred
      sixty patients with esophageal carcinoma, who had undergone esophagectomy and
      reconstruction, were included. These patients were classified according to our
      newly established staging criteria (SN classification), and the clinicopathologic
      features and survival rates were investigated. The 1-, 3, and 5-year survival
      rates in patients classified as SN stage A were 100%, 94.7%, and 88.8%,
      respectively. In patients with stage B, the survival rates were 94.4%, 71.7%, and
      62.2%. In patients in stage C were 72.3%, 33.5%, and 31.3%. In patients with
      stage D, survival rates were 32.4%, 8.9%, and 8.9%. All the comparative analyses
      between stages were significantly different (p = 0.002 for stage A vs. stage B, p
      < 0.0001 for stage B vs. stage C, and p < 0.0001 for stage C vs. stage D).
      Devised staging criteria for esophageal carcinoma providing an excellent
      stratification of disease has been established. The criteria are quite simple and
      convenient for physicians to apply clinically in determining the stage of
      esophageal carcinoma.

PMID- 12796607
TI  - Neoadjuvant doxil chemotherapy prior to androgen ablation plus radiotherapy for
      high-risk localized prostate cancer: feasibility and toxicity.
AB  - Patients with clinical T3 or T4 prostate cancer or with elevated serum prostate
      specific antigen (PSA) levels greater than 40 ng/ml are at high risk of failure
      with primary treatment. Chemotherapy administered at the time of diagnosis may
      decrease the risk of recurrence. Patients with high risk localized prostate
      cancer were treated with two cycles of liposomal doxorubicin (Doxil) at 50 mg/m2
      every 28 days. Patients were assessed for response by digital rectal examination
      (DRE), PSA, and endorectal magnetic resonance imaging (MRI) (erMRI). Patients
      were then treated with androgen ablative therapy and prostate radiotherapy. Seven
      patients were treated. Three patients had T3 disease, and 4 patients had T2b
      disease with either PSA greater than 40 ng/ml or erMRI evidence of seminal
      vesicle involvement or extracapsular disease. Median PSA was 29.4 ng/ml. None of
      the seven patients experienced a significant response, as measured by changes in
      DRE, PSA, or erMRI. Toxicity was significant, with 4 of 7 patients developing
      skin toxicity. All seven patients responded to androgen ablative therapy and
      prostate irradiation. Neoadjuvant liposomal doxorubicin demonstrates no apparent
      activity and significant toxicity. New strategies are needed to improve outcomes
      in high-risk prostate cancer.

PMID- 12796608
TI  - Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients
      with hormone-dependent advanced breast cancer: a prospective, randomized, phase
      III study.
AB  - A prospective phase III trial comparing anastrozole with tamoxifen as first-line
      therapy in postmenopausal, hormone-dependent, advanced breast cancer (ABC).
      Patients were randomized to anastrozole 1 mg daily (n = 121) or tamoxifen 40 mg
      daily (n = 117). Efficacy and tolerability were evaluated after 3 months'
      therapy, and survival was evaluated at median time of follow-up. At a median
      follow-up of 13.3 months, clinical benefit (CB) was achieved in 83% and 56% of
      anastrozole and tamoxifen patients, respectively (p < 0.001); median time to
      disease progression (TTP) in patients achieving CB was 18.0 months and 7.0
      months, respectively, (hazard ratio [HR] = 0.13, 95% CI = 0.08-0.20, p < 0.01).
      At data cutoff, 89% of tamoxifen patients had died, compared with 60% of
      anastrozole patients; median time to death was 17.4 months and 16.0 months,
      respectively (HR = 0.64, 95% CI = 0.47-0.86, p = 0.003). Therapy was well
      tolerated in both groups. Anastrozole showed significant advantages over
      tamoxifen for CB, median TTP in patients gaining CB, and survival. These data
      further support routine use of anastrozole as first-line treatment for
      postmenopausal hormone-dependent ABC.

PMID- 12796609
TI  - Micronucleus response of human glioblastoma and neuroblastoma cells toward low
      LET photon and high-LET p(66)/Be neutron irradiation.
AB  - The identification of photon resistant tumors that are sensitive to neutrons is
      still an unresolved problem, and no radiobiological criteria have been developed
      that could help the selection of patients for neutron therapy. The micronucleus
      (MN) assay has been evaluated for this purpose in a panel of human glioblastoma
      and neuroblastoma cell lines spanning a wide range of photon sensitivities
      defined by mean inactivation doses ([Latin capital letter D with macron
      above][gamma]) of 1.25-3.21 Gy. We show that the relative biologic effectiveness
      (RBE) of the p(66)/Be neutrons is significantly correlated with inherent photon
      sensitivity (r = 0.89, p < 0.01), indicating that the panel of cell lines used is
      suitable to study the differential biologic response to neutrons and photons. We
      find that p(66)/Be neutrons are 1.43 to 5.29 times more effective per unit dose
      in inducing micronuclei than 60Co [gamma]-rays. Surprisingly, cells that are
      inherently photon resistant tend to show a higher yield of micronuclei following
      exposure to either photons or neutrons, but no significant correlation could be
      demonstrated. However, RBE values based on micronucleus yield were found to
      strongly correlate with RBE values derived from cell survival data (r = 0.91, p <
      0.01). It is concluded that although micronucleus yield does not reflect
      intrinsic sensitivity to either photons or neutrons, the strong correlation
      between RBE calculated from micronucleus formation and RBE derived from cell
      survival demonstrates that the micronucleus endpoint has a potential for
      detecting photon resistant cells that show increased sensitivity to neutrons.

PMID- 12796610
TI  - A practical guideline for identifying research intent with projects that collect
      private, identifiable health information.
AB  - Radiation oncologists frequently engage in activities that involve the collection
      and analysis of data from medical records. Access to health information is an
      ethical issue because, if not done according to appropriate guidelines, it
      constitutes an invasion of privacy or breach in confidentiality. To protect
      patients for the social harm that may result from medical record review, our
      society has established laws and regulations that apply to projects that require
      medical record review. A major branch point in the guidelines for such projects
      is whether private information will be collected for research or nonresearch
      purposes. However, a problem with discussing privacy protection in terms of a
      research versus nonresearch model is that it is difficult to make this
      distinction for many kinds of projects. The purpose of this paper is to establish
      a practical guideline that can be used to decide if a project that involves
      analysis of private, identifiable medical information should be considered
      research from the regulatory standpoint.

PMID- 12796611
TI  - Intravascular brachytherapy: a review of the current vascular biology.
AB  - Restenosis is a major limitation of coronary angioplasty, requiring further
      intervention in the majority of cases. Intracoronary radiation has been employed
      in recent years to prevent restenosis lesions with effective results, principally
      in in-stent restenosis. Restenosis is generally considered as an excessive form
      of normal wound healing divided up in processes: elastic recoil, neointimal
      hyperplasia, and negative vascular remodeling. Restenosis has previously been
      regarded as a proliferative process in which neointimal thickening, mediated by a
      cascade of inflammatory mediators and other factors, is the key factor. Data from
      recent studies have pointed to negative vascular remodeling as a major
      contributing factor. Recent studies have also identified particular cell lines
      that might be critical regulators of restenosis, particularly monocyte-derived
      macrophages and myofibroblasts. This review summarizes the current theories of
      vascular biology pertaining to restenosis in coronary arteries and the potential
      mechanisms of why radiation may effectively inhibit restenosis.

PMID- 12796612
TI  - Response to a phase II study of concomitant-to-sequential use of etoposide and
      radiation therapy in newly diagnosed malignant gliomas.
AB  - We evaluated the antitumor efficacy of and patient tolerance to a phase II study
      of concomitant-to-sequential use of etoposide and radiotherapy for newly
      diagnosed malignant gliomas. Fifty-two supratentorial malignant glioma patients
      were enrolled in this phase II study between May 1995 and May 1998. Standard
      cranial irradiation and six courses of etoposide (100 mg/m2 - xdays 1-3) were
      administered. The first course of etoposide was given on days 1 to 3 of
      radiotherapy and was resumed in the week following the end of radiotherapy.
      Treatment was consolidated by further courses of etoposide every 4 weeks. Fifty
      one patients were assessable for toxicity, response, and survival. A complete
      surgical resection was only noted for 17 patients. Six patients had a confirmed
      complete response, and eight patients displayed a partial response. Six patients
      progressed within the first 3 months of starting treatment. The rate of objective
      response for assessable patients with residual tumor was 41.1%. Hematologic
      toxicity was mild; grade 3 or 4 neutropenia was noted in five patients, without
      sepsis. The overall median survival time (MST) was 12.5 months, and the mean
      survival of this population was 14.9 months. These results suggest a certain
      efficacy of this regimen testing a concomitant-to-sequential use of etoposide and
      radiotherapy for newly diagnosed malignant gliomas, and that continued evaluation
      of this combination is warranted, especially because this treatment is also well
      tolerated.

PMID- 12796613
TI  - Commissioning and clinical implementation of a sliding gantry CT scanner
      installed in an existing treatment room and early clinical experience for precise
      tumor localization.
AB  - The primary objective of the present study is to demonstrate that a unique
      computed tomography (CT)-linear accelerator combination can be used to reduce
      uncertainties caused by organ motion and setup inaccuracy. The acceptance,
      commissioning, and clinical implementation of a sliding gantry CT scanner
      installed in an existing linear accelerator room are reported in this paper. A
      Siemens CT scanner was installed directly opposite to an existing accelerator.
      The scanner is movable on a pair of horizontal rails mounted parallel to the
      longitudinal axis of the treatment couch replaced with a carbon fiber tabletop.
      Acceptance and commissioning of the CT scanner were verified with phantom
      studies. For clinical implementation, quality assurance (QA) procedures have been
      instituted to ensure the integrity of the CT gantry axis alignment and the
      accuracy of its movement using a phantom designed in house. A clinical example
      employing the CT-Linac combination to correct the isocenter positioning caused by
      organ motion and setup inaccuracy was presented for a prostate irradiation. Dose
      calculations were performed to study the effects on tumor coverage without the
      adjustments of the isocenter. A summary of the isocenter adjustments for the
      first 30 patients is also presented. The geometric accuracy of the CT scanner is
      < or =1 mm. An isocenter deviation of > or =2 mm from the original plan can be
      detected. For the clinical example of a prostate patient, the average movement of
      the prostate gland was found to be approximately 3mm in the anterior-posterior
      (AP/PA) direction and 5 mm in the cephalic-caudal direction. Variations in the
      isocenter position may result in underdosage of the PTV if correction is not made
      for the change in the isocenter position. Our experience with the first 30
      patients indicates that while the left-right adjustment of the isocenter is
      minimal, in the AP/PA direction, about 33% of treatments required an adjustment
      of 3-5 mm, and about 18% required a 5.1-mm to 10-mm adjustment. In the caudal
      cephalic direction, about 26% required an adjustment of 3-5 mm, and 8% required a
      5.1-mm to 10-mm adjustment. Retrofitting a CT scanner in an existing linear
      accelerator room requires careful planning and well-coordinated efforts from all
      personnel involved. Special QA procedures are needed to ensure the mechanical
      integrity and imaging accuracy of the CT scanner. A CT scan of the patient prior
      to irradiation provides valuable information on organ motion. Any deviations from
      treatment plan can be corrected before dose delivery. Significant deviation from
      the planning isocenter may occur due to daily variations in the rectal filling.
      The CT-Linac combination has significant implications for the treatment of
      prostate cancer.

PMID- 12796614
TI  - Dosimetric evaluation and clinical application of virtual mini-multileaf
      collimator.
AB  - One of the major concerns with multileaf collimators (MLC) is the jagged field
      edge that produces a larger penumbra compared with that produced by a Cerrobend
      block. The dosimetric undulation of the MLC can be minimized by replacing an
      existing MLC with a mini-MLC, an expensive replacement, or by software
      implementation, which essentially converts a regular MLC into a virtual mini-MLC.
      In this study, the dosimetry in the penumbra region of a virtual mini-MLC
      replacing the Cerrobend block is investigated for clinical applications. HD270, a
      software program implemented by Siemens (Concord, CA), combines the use of an MLC
      and a table translation perpendicular to the leaf plane to produce a smooth field
      edge, thus reducing isodose undulation. Three different step resolutions are
      available: 5 mm, 3 mm, and 2 mm. Using film dosimetry, the penumbra regions are
      studied at two different depths for clinical blocks and corresponding MLC setup,
      as well as HD270 with different resolutions for both 6-MV and 15-MV x-ray beams.
      The dose delivery time for HD270 on auto-sequencing mode is compared with the use
      of Cerrobend blocks. The clinical applications of HD270 in head-and-neck (head
      and neck) and prostate treatments are investigated. For single-field irradiation,
      the 80-20% penumbra widths for both the 45 degrees block and the circular block
      are reduced with HD270 compared with MLC for both 6 and 15 MV at different
      depths. At 2-mm resolution, the scalloping isodose lines (IDLs) with MLC
      completely disappear, although the penumbra is still larger than the Cerrobend
      block. On the other hand, the difference in dose undulations between 2-mm and 3
      mm resolution is small. In the head and neck irradiation, the 80-20% widths with
      HD270 are 1 to 2 mm less than MLC, but they are still 2 mm wider than with a
      Cerrobend block. The 50% IDL is reduced by 2 mm with HD270 compared with MLC,
      which provides safety near spinal cord. Dose-volume histogram (DVH) calculations
      for the different shielding techniques indicate that the HD270 improves the
      spinal cord dose distribution significantly compared with MLC. A similar
      improvement in dose undulation is observed for the prostate case. In the dose
      region, >60% of the prescribed dose, there is approximately 10% less irradiated
      volume for the rectum when HD270 (3 mm resolution) is employed compared with MLC.
      The treatment time was compared with that from the Cerrobend block, and it was
      found that even at 3-mm resolution, there is a 20% reduction in treatment time in
      a head and neck treatment; with a 2-mm resolution, there is a 15% increase in
      time. The isodose undulation due to MLC can be significantly reduced with the
      HD270. Clinical application with HD270 for head and neck and prostate irradiation
      provides a smaller penumbra region compared with MLC, although it still gives a
      larger one compared with the Cerrobend block. In the clinical cases presented in
      this study, the 3-mm resolution is the most effective in improving the penumbra
      and delivery time. The HD270 implementation is a versatile and cost-effective
      solution for reducing MLC undulation.

PMID- 12796615
TI  - Targeting angiogenic processes by combination low-dose paclitaxel and radiation
      therapy.
AB  - Tumor growth and angiogenesis are interdependent. Paclitaxel and radiation
      therapy are commonly used in the clinic, in a number of disease sites, requiring
      high dosages of both drug and radiation for cure. Paclitaxel (Taxol) is a
      diterpenoid with antitumor activity against a variety of human neoplasms and can
      amplify the cytotoxic effect of ionizing radiation in vitro, presumably by
      inducing arrest at metaphase, known to be a very radiosensitive phase of the cell
      cycle. Little is known about how angiogenesis is affected by paclitaxel when the
      combination of paclitaxel and radiation are used. We have evaluated the
      combination of paclitaxel and radiation at various concentrations, on cytokine
      induced angiogenesis in vitro with the goal of determining whether reduction of
      radiation and paclitaxel doses is possible without sacrificing efficacy. We have
      found that paclitaxel inhibited endothelial cell proliferation, migration, and
      tube formation (differentiation) at one-tenth the concentration needed to achieve
      a similar effect on tumor cell lines. In combination with radiation, inhibition
      of endothelial cell function was additive and increased twofold. The combination
      of low-dose paclitaxel and radiation suggests a complementary strategy with
      potential clinical ramifications to target angiogenesis-dependent malignancies.

PMID- 12796616
TI  - Does the addition of glutamine to total parenteral nutrition have beneficial
      effect on the healing of colon anastomosis and bacterial translocation after
      preoperative radiotherapy?
AB  - Glutamine administration stimulates mucosal growth and preserves the morphology
      of the intestine. Theoretically, it could improve colonic anastomotic healing
      after radiotherapy (RT)-induced epithelial damage and mucosal atrophy induced by
      total parenteral nutrition (TPN). To investigate this issue, the rectosigmoid
      colon in male Wistar rats was irradiated to a total dose of 25 Gy. Five days
      after the end of RT, side-to-side anastomosis was constructed between the
      irradiated rectosigmoid and the nonirradiated caecum. Postoperatively, animals
      were divided in three groups: group I, normal diet orally; group II, TPN; group
      III, TPN enriched with 2% glutamine (Gln-TPN). All animals decreased in weight
      during RT and after surgery. Weight regain postoperatively was better in the
      orally fed animals in comparison with the parenterally fed animals (I vs. II and
      III; p < 0.01). Colonic anastomotic bursting pressure (BP) and bursting wall
      tension (BWT) were significantly less in group II in comparison with groups I and
      III (II vs. I and III; p < 0.01). BP and BWT were comparable in groups I and III.
      No significant differences were found between all the groups in gut bacterial
      translocation to the blood or to the mesenterical lymph nodes. Conclusively, Gln
      TPN can play a role in counteracting the negative effect of food deprivation on
      the healing of irradiated colonic anastomoses. Postoperative Gln-TPN does not
      influence gut bacterial translocation in this rat model.

PMID- 12796617
TI  - Oligodendroglioma: does deferring treatment compromise outcome?
AB  - This study reports the University of Florida experience treating
      oligodendrogliomas with the goal of identifying the factors that predict
      favorable outcome. Between 1958 and June 1998, 51 patients (aged 5-75 years) were
      diagnosed with pure oligodendroglioma at the University of Florida. Histologic
      grade was anaplastic in 19 patients, low-grade in 30 patients, and unknown in one
      patient. Twelve patients were treated with surgery alone (10 with low-grade
      tumors). Thirty-nine patients underwent postoperative radiotherapy after surgery
      (plus chemotherapy in four patients). A biopsy was performed in 10 patients, 40
      underwent subtotal or gross total resection, and one had surgery of unknown
      extent. Thirteen patients with a radiographic abnormality consistent with a low
      grade glioma had the initiation of definitive treatment (i.e., surgery with or
      without radiotherapy) deferred for a median of 4.5 years before undergoing
      treatment for worsening symptoms or radiographic progression. Absolute survival
      for the entire group (51 patients) at 5, 10, and 20 years from the date of
      initial treatment was 61%, 37%, and 31%, respectively, and at 5, 10, and 20 years
      from the date of initial diagnosis was 65%, 43%, and 34%, respectively. No
      patient died of intercurrent disease. Multivariate analysis for absolute survival
      from the time of initial treatment demonstrated young age (young patients fared
      better than older patients) and size (<5 cm better than > or =5 cm) to be
      significant variables. No patient under the age of 21 years (n = 8) at the time
      of diagnosis has died in this series. Deferring aggressive treatment did not
      alter survival. Multivariate analysis for favorable absolute survival based on
      the time from initial diagnosis demonstrated young age and presentation with
      seizures alone to be statistically significant for favorable outcomes.
      Approximately one third of patients with oligodendroglioma appear to be cured
      with aggressive treatment. Age is the most important predictor of long-term
      progression-free and absolute survival with young patients (especially aged <21
      years) doing much better than older patients. Deferring aggressive treatment
      (surgery and/or radiation) until symptoms clearly indicate tumor progression does
      not compromise outcome for a select group of patients who are diagnosed at a
      young age with a nonenhancing mass on MR and seizures as the lone presenting
      symptom.

PMID- 12796618
TI  - Where is the wisdom?

PMID- 12796619
TI  - Chicken soup cure may not be a myth.

PMID- 12796620
TI  - Older HIV patients face metabolic complications.

PMID- 12796621
TI  - Summer is prime time for diving injuries.

PMID- 12796622
TI  - Diagnose and manage autistic children.

PMID- 12796623
TI  - PTH revisited for osteoporosis treatment.

PMID- 12796624
TI  - Take action against refused prescriptions.

PMID- 12796625
TI  - Is it scabies? How to tell.

PMID- 12796626
TI  - Decertification: management's role when employees rethink unionization.

PMID- 12796627
TI  - Work-related attributes of RN job satisfaction in acute care hospitals.

PMID- 12796628
TI  - Salary compression: its effect on nurse recruitment and retention.

PMID- 12796629
TI  - Vision 2020, part I: profile of the future nurse leader.
AB  - The demand for knowledgeable and skilled nursing leaders at the first, middle,
      and executive levels of management in healthcare organizations drove a multi
      phased project about the kinds of nurse managers who will be needed in the future
      and their educational needs. This first article in a two-part series describes
      seasoned nurse leaders' opinions about the educational preparation, experiences,
      and competencies desired in nurse managers for the year 2020.

PMID- 12796630
TI  - Measuring staff nurse decisional involvement: the Decisional Involvement Scale.
AB  - Key organizations and new legislation are promoting staff nurse involvement in
      decisions about nursing practice and patient care as a long-term strategy to
      improve the culture of the work environment. The authors discuss the Decisional
      Involvement Scale (DIS), a multipurpose measure that can be used as a diagnostic
      tool, an organizational development strategy, and an evaluative instrument. In
      addition, support to substantiate the DIS as a valid and reliable measure is
      summarized.

PMID- 12796631
TI  - Role stress and career satisfaction among registered nurses by work shift
      patterns.
AB  - OBJECTIVE: This study examined the variation in role stress and career
      satisfaction among hospital-based registered nurses (RNs) by shift length.
      SUMMARY BACKGROUND DATA: Many hospitals have reorganized care delivery into 12
      hour work shifts to improve RN recruitment, retention, and cost effectiveness.
      Yet little is known about the effects of 12-hour shifts on RN role stress and
      career satisfaction. As an unprecedented RN shortage approaches, factors that
      contribute to satisfying and healthy practice environments must be identified.
      METHODS: This study used a descriptive cross-sectional research design. Five
      hundred RNs were randomly selected to receive a mailed questionnaire packet.
      RESULTS: Initial findings indicate RNs working 12-hour shifts were younger, less
      experienced, and more stressed than colleagues working 8-hour shifts. When
      differences in nursing experience were controlled, similar RN stress levels were
      found. Although overall career satisfaction was comparable between groups,
      significant differences were found in the areas of salary and professional
      status. Pay, autonomy, and professional status were the most important
      determinants of career satisfaction for all RN participants. CONCLUSIONS: These
      findings suggest that RNs may experience greater professional fulfillment when
      strategies are implemented that promote autonomous practice environments, provide
      financial incentives, and recognize professional status. Proactive decision
      making may avert RN disillusionment and avoid other negative consequences that
      impact quality of care.

PMID- 12796632
TI  - The art of decision-making.
AB  - As important as sound decision-making is, many executives neglect to utilize any
      formal decisionmaking process. As many executives know, making the wrong decision
      can be disastrous, if not career ending. In today's high-pressure, complex, and
      challenging healthcare environment, it makes sense to follow a tried and true
      process for making decisions. The author examines the traditional method of
      problem identification, setting objectives, listing alternatives and
      consequences, and selecting the best solution in the decision-making process as
      well as new research in this field.

PMID- 12796633
TI  - A buddy program for international nurses.
AB  - To help alleviate the nursing shortage, nurses from overseas are being recruited.
      These nurses must adjust to numerous cultural, social, and organizational
      experiences. Using Pilette's phases of adjustment and a theoretical framework,
      the author discusses a Buddy Program that has been instituted in a community
      hospital to provide support and resources to help international nurses with their
      earliest phase of acculturation.

PMID- 12796634
TI  - Advice nursing practice: on the quality of the evidence.
AB  - OBJECTIVE: The primary objective was to review the research regarding advice
      nursing practice to determine the content areas investigated and the quality of
      the evidence. METHODS: A systematic review of advice nursing research was done in
      electronic databases, reference lists, and the literature identified by experts
      (N = 527). After deletion of duplicates and clinical and theoretical articles,
      full text reviews were done on 62 studies. RESULTS: Eight thematic content areas
      were identified: delivery and continuity of care to populations, appropriateness
      of advice given, patient/provider satisfaction, disposition/utilization after
      calls, reason for calling, cost analysis, process of decision-making, and
      documentation. The most frequently investigated subject was delivery/continuity
      of care (n = 16). IMPLICATIONS: For certain chronic disease populations,
      interventions using telephone advice for social support, education, and symptom
      management improve clinical outcomes. Availability and use of protocols and
      guidelines do not guarantee standardized care or ensure that appropriate advice
      will be given. Consumer satisfaction with advice nursing is high, and appears to
      be related to the intervention component of the nursing process. The priority for
      future research should be given to those studies that describe the character and
      suitable dose of the nursing intervention that is advice nursing.

PMID- 12796635
TI  - Increasing incidence of testicular cancer worldwide: a review.
AB  - PURPOSE: Testicular cancer (TC) is the most common malignancy in 20 to 34-year
      old men. Numerous publications have shown an increase in the incidence of testis
      cancer in the last 40 years with substantial differences among countries. We
      evaluated worldwide variations in testicular cancer incidence and compared trends
      in different regions in the world. MATERIALS AND METHODS: We reviewed 441 studies
      provided by a MEDLINE search using the key words testis/testicular, cancer/tumor
      and incidence that were published between 1980 and 2002. From these articles we
      selected only those devoted to testis cancer incidence and of them only the most
      recent studies from each country or region. Nevertheless, articles using the same
      data base but providing new and additional information, for example differences
      among ethnic groups or controversial explanations for trends, were also retained.
      We selected 30 articles and analyzed their methodological approach and main
      results. RESULTS: Worldwide we observed a clear trend toward an increased TC
      incidence in the last 30 years in the majority of industrialized countries in
      North America, Europe and Oceania. Nevertheless, surprising differences in
      incidence rates were seen between neighboring countries (Finland 2.5/100,000
      cases versus Denmark 9.2/100,000) as well as among regions of the same country
      (2.8 to 7.9/100,000 according to various regional French registers). In addition,
      substantial differences in the TC incidence and trends were observed among ethnic
      groups. The increase in the TC incidence was significantly associated with a
      birth cohort effect in the United States and in European countries. To date
      except for cryptorchidism no evident TC risk factor has been clearly
      demonstrated, although the environmental hypothesis with a key role of endocrine
      disrupters has been put forward by several groups. CONCLUSIONS: Such a recent
      increase in the TC rate in most industrialized countries should lead urologists
      and andrologists to give more attention to testicular cancer symptoms in
      adolescents and young adults. In a public health perspective further research
      using cases collected through national and regional population based registers
      and case-control studies must be strongly encouraged if we wish to be able to
      assess future trends in TC incidence rates and also identify risk factors.

PMID- 12796636
TI  - Histological changes of minimally invasive procedures for the treatment of benign
      prostatic hyperplasia and prostate cancer: clinical implications.
AB  - PURPOSE: Benign prostatic hyperplasia (BPH) is near universal in aging men,
      creating tremendous costs in morbidity and surgical treatment. In the last decade
      numerous nonsurgical minimally invasive methods have emerged for ablation of
      prostatic tissue. MATERIALS AND METHODS: We reviewed the recently published
      English language literature on minimally invasive techniques for treating BPH and
      cancer with an emphasis on histopathological findings. RESULTS: We compared the
      spectrum of contemporary minimally invasive treatments for BPH and cancer, with
      an emphasis on histopathological results. Clinical results were summarized
      briefly for each treatment method. These procedures ablate tissue by thermal,
      cryogenic, chemical or enzymatic injury. The 5-year results for some techniques
      were promising, although long-term durability is still uncertain, and other
      methods were in preclinical or early clinical stages. Invariably the treated
      tissue was devitalized with a thin border of granulation tissue and fibrosis.
      These procedures have applications for BPH and prostate cancer, although some
      studies are limited to only 1 disease. CONCLUSIONS: Minimally invasive procedures
      show promise of a durable replacement for surgical resection.

PMID- 12796637
TI  - Ureteral endometriosis.
AB  - PURPOSE: This review discusses the pathophysiology, presentation, and different
      minimally invasive medical and surgical treatment options for ureteral
      endometriosis. MATERIALS AND METHODS: A comprehensive literature review of
      reports on the diagnosis and management of ureteral endometriosis was performed
      using MEDLINE. RESULTS: Ureteral endometriosis is a rare disease. Most cases
      present with silent obstruction, as opposed to cyclical hematuria. The diagnosis
      of ureteral endometriosis requires a high index of suspicion. A variety of
      diagnostic tests can help identify the extent of disease and the degree of renal
      function on the side of ureteral involvement. CONCLUSIONS: Ureteral endometriosis
      can be treated with hormones or surgical intervention. While surgery is reserved
      for hormone refractory cases and obstruction associated with extensive scarring,
      the majority of cases can be managed with hormones only. A combination of
      hormones and surgery is also effective. Surveillance for obstructive uropathy
      with periodic noninvasive monitoring of kidney function is currently recommended
      for all patients with endometriosis.

PMID- 12796638
TI  - Pathophysiology of priapism: dysregulatory erection physiology thesis.
AB  - PURPOSE: While a modest amount of medical literature has been written on the
      topic of priapism, reports heretofore have focused predominantly on diagnostic
      and management related aspects of the disorder, providing meager information in
      regard to its pathophysiology. Accordingly the intent of this review was to
      explore the etiological and pathogenic factors involved in priapism. MATERIALS
      AND METHODS: The review entailed an overview of traditional and modern concepts
      that have been applied to the pathophysiology of priapism and an evaluation of
      assorted observational and experimental data relating to this field of study. The
      basic exercise consisted of a literature search using the National Library of
      Medicine PubMed Services, index referencing provided through the Historical
      Collection of the Institute of Medicine of The Johns Hopkins University and a
      survey of abstract proceedings from national meetings relevant to priapism.
      RESULTS: Insight into the pathophysiology of priapism was derived from a
      synthesis of evolutionary clinical experiences, mythical beliefs, clinical
      variants and scientific advances associated with the field of priapism. The
      results can be summarized. 1) Clinicopathological manifestations of priapism
      support its basic classification into low flow (ischemic) and high flow
      (nonischemic) hemodynamic categories, commonly attributed to venous outflow
      occlusion and unregulated arterial overflow of the penis, respectively. 2)
      Factual information is insufficient to substantiate etiological roles for
      urethral infection, bladder distention, failed ejaculation, satyriasis and sleep
      apnea in priapism. 3) Features of the variant forms of priapism invoke changes in
      nervous system control of erection and penile vascular homeostasis as having
      pathogenic roles in the disorder. 4) Clinical therapeutic and basic science
      investigative studies have revealed various effector mechanisms of the erectile
      tissue response that may act in dysregulated fashion to subserve priapism.
      CONCLUSIONS: This exercise suggested that, while priapism is commonly defined in
      terms of adverse mechanical contexts affecting penile circulation, it may also be
      viewed at least in some situations as an unbalanced erectile response involving
      derangements in possibly diverse systems of regulatory control. An integrative
      scientific approach that encompasses tissular, cellular and molecular levels of
      investigation may allow further understanding of the pathophysiology of the
      disorder. Ongoing elucidation of this pathophysiology can be expected to promote
      the development of new priapism therapies.

PMID- 12796639
TI  - Risk factors for patients with pelvic lymph node metastases following radical
      cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density.
AB  - PURPOSE: We evaluated the clinical outcomes and risk factors for progression in a
      large cohort of patients with lymph node metastases following en bloc radical
      cystectomy and bilateral pelvic lymphadenectomy. MATERIALS AND METHODS: From July
      1971 through December 1997, 1,054 patients underwent radical cystectomy and
      bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell
      carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66
      years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the
      244 patients (57%) received some form of chemotherapy. At a median followup of
      greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate
      analysis according to tumor grade, carcinoma in situ, primary bladder tumor
      stage, pathological subgroups, total number of lymph nodes removed and involved
      with tumor, and lymph node density (total number of positive lymph nodes/total
      number removed). In addition, the form of urinary diversion and the
      administration of chemotherapy were also evaluated. Multivariate analysis was
      then performed to analyze these variables independently. RESULTS: The incidence
      of positive lymph nodes increased with higher p stage and pathological subgroups.
      Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%)
      with extravesical tumor extension had involved lymph nodes. The median number of
      lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96),
      while the median number of positive lymph nodes was 2 (range 1 to 63). Overall
      recurrence-free survival at 5 and 10 years for the 244 patients with lymph node
      positive disease was 35% and 34%, respectively. Patients with lymph node positive
      disease and an organ confined primary bladder tumor had significantly improved 10
      year recurrence-free survival compared with those with extravesical tumor
      extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at
      surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25%
      10-year recurrence-free survival compared with 36% when greater than 15 lymph
      nodes were removed. Recurrence-free survival at 10 years for patients with 8 or
      less positive lymph nodes was significantly higher than in those with greater
      than 8 positive lymph nodes (40% vs 10%, p <0.001). The novel concept of lymph
      node density was also a significant prognostic factor. Patients with a lymph node
      density of 20% or less had 43% 10-year recurrence-free survival compared with
      only 17% survival at 10 years when lymph node density was greater than 20% (p
      <0.001). On multivariate analysis the total number of lymph nodes involved,
      pathological subgroups of the primary bladder tumor, lymph node density and
      adjuvant chemotherapy remained significant and independent risk factors for
      recurrence-free and overall survival. CONCLUSIONS: Patients with lymph node tumor
      involvement following radical cystectomy may be stratified into high risk groups
      based on the primary bladder tumor, pathological subgroup, number of lymph nodes
      removed and total number of lymph nodes involved. Lymph node density, which is a
      novel prognostic indicator, may better stratify lymph node positive cases because
      this concept collectively accounts for the total number of positive lymph nodes
      (tumor burden) and the total number of lymph nodes removed (extent of
      lymphadenectomy). Future staging systems and the application of adjuvant
      therapies in clinical trials should consider applying lymph node density to help
      standardize this high risk group of patients following radical cystectomy.

PMID- 12796640
TI  - Correlation between glomerular size and long-term renal function in patients with
      substantial loss of renal mass.
AB  - PURPOSE: Focal segmental glomerulosclerosis and progressive renal failure have
      been reported in reduced renal mass models. However, these findings are not
      consistent across all species. Increased intracapillary pressure and chronic
      glomerular hyperfiltration have been shown to contribute to this progression.
      Studies also have shown that a strong correlation exists between higher
      glomerular size and the degree of glomerular sclerosis that develops following
      loss of functioning nephrons. MATERIALS AND METHODS: To evaluate the relationship
      between glomerular size and long-term renal function following massive renal mass
      removal we describe 9 patients with less than 50% renal mass. All patients had
      undergone initial nephrectomy followed by partial second nephrectomy, with 30% to
      50% of the second kidney excised for localized tumor. RESULTS: In 3 patients
      moderate to severe renal failure developed. Mean planar glomerular area (MPA) was
      29.45 +/- 2.2 mm3 for all patients. Multivariate linear regression analysis
      demonstrated a significant association between MPA 30 mm3 or greater and
      increased serum creatinine. For patients with MPA 30 mm3 or greater the predicted
      delta creatinine was 2.43 mg/dl higher than that in patients with MPA less than
      30 mm3 (p = 0.0028). Age was the only other covariate significantly associated
      with outcome in multivariate analysis. CONCLUSIONS: Our data indicate an
      individual susceptibility toward developing renal failure after significant renal
      mass reduction. We suggest that patients with less than 50% renal mass and higher
      MPA are at greater risk for progressive renal failure. MPA may be used as a
      marker in high risk patients with substantial loss of renal mass to predict long
      term renal function.

PMID- 12796641
TI  - Computerized tomography guided access for percutaneous nephrostolithotomy.
AB  - PURPOSE: Access for percutaneous nephrostolithotomy (PNL) using conventional
      fluoroscopic guidance may carry an increased risk of damage to surrounding organs
      in patients with renal calculi and aberrant anatomy. In these situations cross
      sectional anatomical imaging may facilitate safe percutaneous access. We describe
      our experience with computerized tomography (CT) guided percutaneous access for
      such patients undergoing PNL. MATERIALS AND METHODS: Between June 2000 and
      December 2001, 154 patients underwent PNL at our institution. Five of these
      patients (3%) required a total of 6 percutaneous access tracks under CT guidance.
      All patients in this group had anatomical abnormalities precluding standard
      access to the collecting system without risk to adjacent organs. These
      abnormalities included a retrorenal colon in 2 and a severely distorted body
      habitus due to spinal dysraphism in 3. RESULTS: Percutaneous access was achieved
      without complication in all cases. At subsequent PNL 5 of the 6 renal units (83%)
      were rendered completely stone-free. CONCLUSION: CT guided percutaneous access is
      infrequently required for PNL. However, there is a select group of patients with
      anatomical anomalies that may predictably require this procedure to facilitate
      safe and efficacious PNL.

PMID- 12796642
TI  - Percutaneous management of calculi within horseshoe kidneys.
AB  - PURPOSE: Percutaneous treatment of patients with calculi in a horseshoe kidney
      can be challenging due to the altered anatomical relationship in the
      retroperitoneum. Therefore, we performed a multi-institutional review to assess
      the safety and efficacy of this minimally invasive technique. MATERIALS AND
      METHODS: Of 37 patients identified with calculi in a horseshoe kidney at 3
      institutions 24 (65%) underwent percutaneous nephrolithotripsy as primary
      treatment. Average patient age was 48.4 years and 75% of the patients were male.
      In 3 patients with staghorn calculi mean stone size as measured by computed
      digitized stone surface area was 448 mm2. Mean followup was 5.8 months. The stone
      free rate, complication rate, need for secondary intervention and stone
      composition were evaluated. RESULTS: Renal access was obtained through an upper
      pole calix in 63% of the cases, a lower calix in 25% and a middle calix in 4%.
      Access location was not documented in 1 patient (4%). Of the 24 patients 21
      (87.5%) were rendered stone-free after primary or second look procedures.
      Flexible nephroscopy was used in 84% of cases. Minor complications occurred in 4
      patients (16.7%), whereas 3 (12.5%) experienced major complications, including
      significant bleeding necessitating early cessation, nephropleural fistula and
      pneumothorax. No deaths occurred as a result of this treatment choice. Stone
      analysis was available for 21 cases (87.5%). Calcium stones predominated (87.5%),
      followed by uric acid (9.5%) and struvite (4.8%). CONCLUSIONS: Percutaneous
      treatment of patients with renal calculi in a horseshoe kidney is technically
      challenging, usually requiring upper pole access and flexible nephroscopy due to
      the altered anatomical relationships of the fused renal units. The success rate
      based on stone-free results and a relatively low incidence of major complications
      suggest that this minimally invasive management option is an effective means of
      stone management in this complex patient population.

PMID- 12796643
TI  - Laparoscopic ice slush renal hypothermia for partial nephrectomy: the initial
      experience.
AB  - PURPOSE: We describe a novel technique of laparoscopic renal hypothermia with
      intracorporeal ice slush during partial nephrectomy as well as clinical
      experience with the initial 12 patients. MATERIALS AND METHODS: A total of 12
      select patients with an infiltrating renal tumor who were candidates for nephron
      sparing surgery underwent transperitoneal laparoscopic partial nephrectomy with
      renal hypothermia. An Endocatch II (United States Surgical Corp., Norwalk,
      Connecticut) bag was placed around the mobilized kidney and its drawstring was
      cinched around the intact renal hilum. The renal artery and vein were occluded en
      bloc with a Satinsky clamp. The bottom of the engaged bag was retrieved through a
      12 mm port site and opened, and ice slush was introduced within the bag to
      completely surround the kidney. After renal hypothermia was achieved laparoscopic
      partial nephrectomy was performed by duplicating open surgical techniques. Renal
      parenchymal temperature was measured using a thermocouple needle in 5 patients.
      Median tumor size was 3.2 cm (range 1.5 to 5.5), 6 tumors (50%) were central in
      location and an imperative indication for partial nephrectomy was present in 7
      patients (58%). RESULTS: All procedures were successfully completed
      laparoscopically without open conversion. Median time to deploy the bag around
      the kidney was 7 minutes (range 5 to 20), the median volume of ice slush
      introduced was 600 cc (range 300 to 750) and the time needed to insert the ice
      slush was 4 minutes (range 3 to 10). Median blood loss was 200 cc, total ischemia
      time was 43.5 minutes (range 25 to 55) and total operative time was 4.3 hours
      (range 3 to 5.5). Nadir renal parenchymal temperature was 5C to 19C and the mean
      decrease in systemic temperature was 0.6C. Histopathology confirmed renal cell
      carcinoma in 11 patients (92%), of whom all had negative surgical margins.
      Intraoperative complications occurred in 2 initial patients, including partial
      bag slippage in 1 and Satinsky clamp malfunction in 1. Postoperatively renal scan
      confirmed a functioning ipsilateral kidney in all cases. CONCLUSIONS: To our
      knowledge we present the initial clinical report of laparoscopic renal
      hypothermia for partial nephrectomy. By replicating standard open surgical
      practice our intracorporeal ice slush technique has the potential to extend the
      scope of laparoscopic partial nephrectomy to more complicated renal tumors.

PMID- 12796644
TI  - Prospective comparison of 3-dimensional volume rendered computerized tomography
      and conventional renal arteriography for surgical planning in patients undergoing
      laparoscopic donor nephrectomy.
AB  - PURPOSE: We prospectively assessed the accuracy of 3-dimensional (3-D) volume
      rendered computerized tomography (CT) and conventional renal arteriography to
      visualize renovascular anatomy in patients undergoing laparoscopic donor
      nephrectomy. MATERIALS AND METHODS: A total of 60 consecutive patients undergoing
      laparoscopic donor nephrectomy (left side in 46 and right side in 14)
      prospectively underwent 3-D CT and renal angiography. A short videotape of 3-D CT
      was prepared using volume rendering software that demonstrated the anatomical
      location, number, anomalies and spatial interrelationships of the renal arteries
      and veins. These 3-D videotapes and arteriogram findings were directly correlated
      with intraoperative surgical findings at laparoscopy and during ex vivo bench
      preparation of the harvested kidney. The perceived intraoperative value of 3D-CT
      to delineate renovascular anatomical detail was scored subjectively by the
      laparoscopic surgeon for each case on a 10-point scale of 0--completely
      inaccurate to 10--completely accurate. RESULTS: There were no complications
      related to the 3-D CT protocol and volume rendering was successful in all
      patients. Three-D CT accurately identified the number of renal arteries in 59
      patients (98%). In 1 patient with 3 renal arteries 3-D CT and arteriogram each
      identified only 2. In the 46 patients undergoing left donor nephrectomy 3-D CT
      accurately identified the number of veins and venous anomalies in 45 (98%),
      including 2 with a circumaortic left renal vein. Another case of circumaortic
      vein was misdiagnosed as 2 renal veins. On the right side in 14 patients 3-D CT
      accurately identified the renal veins in 13 (94%) and missed 1 vein in a patient
      with 2 renal veins. Angiography correctly identified the number of renal veins in
      only 52 cases (87%). Furthermore, it misdiagnosed all 3 cases of circumaortic
      left renal vein. The laparoscopic surgeon believed that 3-D CT accurately
      identified the location and anatomical interrelationship of the renal vessels
      with precision. Mean subjective score +/- SEM was 8.5 +/- 1 for the arterial
      system, 8.6 +/- 1.1 for the venous system and 9.2 +/- 0.5 for any vascular
      anomalies. CONCLUSIONS: Three-D CT accurately identifies renal vascular anatomy
      in a manner that may facilitate renal hilar dissection during laparoscopic donor
      nephrectomy, especially during the initial surgeon experience. This imaging
      modality integrates essential information from angiography, venography and
      excretory urography into a single study, and it can obviate the need for more
      invasive vascular imaging in most cases.

PMID- 12796645
TI  - Optical access trocar injuries in urological laparoscopic surgery.
AB  - PURPOSE: Inadvertent injuries during trocar and Veress needle placement are a
      rare but potentially serious complication of laparoscopic surgery. An access
      alternative is an optical trocar under direct vision. Limited data are available
      regarding the safety of this technique. We reviewed complications related to
      optical access trocars during standard transperitoneal urological laparoscopic
      procedures performed at a single institution. MATERIALS AND METHODS: From 1995 to
      2001 the optical access trocar was used as the initial trocar in 1,283 urological
      laparoscopic procedures. The procedures included simple and radical nephrectomy
      in 309 cases, donor nephrectomy in 386, partial nephrectomy in 79, pyeloplasty in
      173 and various other procedures in 336. Intra-abdominal complications caused by
      optical access trocar were assessed. RESULTS: The optical trocar was inserted at
      the umbilicus in 88 patients (7.4%), in the right upper quadrant in 445 (34.7%)
      and in the left upper quadrant in 750 (58.5%). There were 4 injuries (0.31%)
      associated with the optical access trocar. Complications occurred on the left
      side in 3 cases and on the right side in 1, including 1 injury to bowel, 1
      mesenteric injury resulting in a retroperitoneal hematoma and 2 injuries to
      epigastric vessels. Three cases were recognized and repaired immediately but in a
      case of epigastric vessel injury the expanding abdominal wall hematoma required
      postoperative repair. CONCLUSIONS: Optical access trocars provide a safe and
      rapid technique for initial trocar placement. Results of this large series
      support the finding that few trocar related complications are associated with the
      optical access trocar.

PMID- 12796646
TI  - Comparative analysis of laparoscopic versus open partial nephrectomy for renal
      tumors in 200 patients.
AB  - PURPOSE: Laparoscopic partial nephrectomy is an emerging minimally invasive,
      nephron sparing approach for renal cell carcinoma. We compared perioperative
      outcomes after laparoscopic and open nephron sparing surgery (NSS) for patients
      with a solitary renal tumor of 7 cm or less at a single institution. MATERIALS
      AND METHODS: Since September 1999, 100 consecutive patients have undergone
      laparoscopic partial nephrectomy for a sporadic single renal tumor of 7 cm or
      less at our institution. A contemporary cohort of 100 consecutive patients with
      similar inclusion criteria have undergone open NSS since April 1998. Since our
      laparoscopic technique was based on our established open surgical principles, the
      2 approaches were similar, including transient renal vascular control, sharp
      tumor excision in a bloodless field, pelvicaliceal repair when necessary, suture
      ligation of transected intrarenal blood vessels and suture repair of the renal
      parenchymal defect over a bolster. Demographic, intraoperative, postoperative and
      short-term followup data were retrospectively compared between the 2 groups.
      RESULTS: Median tumor size was 2.8 cm in the laparoscopic group and 3.3 cm in the
      open group (p = 0.005). There were significantly more tumors greater than 4 cm in
      the open group (p <0.001). There were more patients with a solitary kidney in the
      open surgical group (p = 0.002). More patients in the open group underwent NSS
      for a malignant tumor (p = 002). Comparing the laparoscopic versus open groups,
      median surgical time was 3 vs 3.9 hours (p <0.001), blood loss was 125 vs 250 ml
      (p <0.001) and mean warm ischemia time was 27.8 vs 17.5 minutes (p <0.001),
      respectively. In the laparoscopic and open groups median analgesic requirement
      was 20.2 vs 252.5 mg morphine sulfate equivalents (p <0.001), hospital stay was 2
      vs 5 days (p <0.001) and average convalescence was 4 vs 6 weeks (p <0.001).
      Median preoperative serum creatinine (1.0 vs 1.0 mg/dl, p = 0.52) and
      postoperative serum creatinine (1.1 vs 1.2 mg/dl, p = 0.65) were similar in the 2
      groups. No kidney was lost due to warm ischemic injury. Three patients in the
      laparoscopic group had a positive surgical margin compared to none in the open
      groups (3% vs 0%, p = 0.1). Laparoscopic NSS was associated with a higher rate of
      major intraoperative complications (5% vs 0%, p = 0.02). There were no
      significant differences in overall postoperative complications, although
      renal/urological complications were more common in the laparoscopic group (11% vs
      2%, p = 0.01). CONCLUSIONS: Open surgical partial nephrectomy remains the
      established standard for nephron sparing treatment of renal tumors. When applied
      to small renal tumors, the laparoscopic approach is associated with longer warm
      renal ischemia time, more major intraoperative complications and more
      postoperative urological complications. Our data also suggest that more
      deliberate efforts to achieve a wider surgical margin are necessary with the
      laparoscopic approach. Nevertheless, our data suggest that laparoscopic NSS is
      emerging as an effective, minimally invasive therapeutic approach with respect to
      renal functional outcome with the additional advantages of decreased
      postoperative narcotic use, earlier hospital discharge and a more rapid
      convalescence. Continued efforts are required to develop laparoscopic renal
      hypothermia techniques and facilitate intrarenal suturing, while minimizing warm
      ischemia time.

PMID- 12796647
TI  - Contrast enhanced color Doppler endorectal sonography of prostate: efficiency for
      detecting peripheral zone tumors and role for biopsy procedure.
AB  - PURPOSE: We evaluated the accuracy of contrast enhanced color Doppler endorectal
      ultrasound to guide biopsy for the detection of prostate cancer. MATERIALS AND
      METHODS: A total of 85 patients were evaluated with gray scale and color Doppler
      before and during intravenous injection of ultrasound contrast agent made of
      galactose based air microbubbles. Our biopsy protocol was performed during
      contrast injection. An additional 18 directed cores were obtained based on
      contrast enhanced imaging. Diagnostic efficiency with and without contrast medium
      injection for detecting prostate cancer were compared based on biopsy results.
      RESULTS: Cancer was identified in a total of 58 biopsy sites in 54 patients. Gray
      scale imaging revealed 96 abnormal hypoechoic nodules or irregular zones inside
      the outer gland, of which 48 were malignant on pathological evaluation. Contrast
      enhanced color Doppler had higher sensitivity (93%) than unenhanced color Doppler
      (54%), while specificity increased only 79% to 87% for enhanced imaging. Nine of
      10 isoechoic suspicious zones were depicted with enhancement, while unenhanced
      Doppler detected 7 of them. There was no significant difference between the
      intensity of enhancement and tumor Gleason scores. CONCLUSIONS: Contrast enhanced
      color Doppler endorectal sonography increases the detection of prostate cancer.
      Improvement in sensitivity was high, while the difference in specificity was not
      as pertinent. It is accurate when using a common and routine application
      ultrasound unit. This technique is easy to perform and not time-consuming.
      Obtaining additional biopsy cores of suspicious enhancing foci significantly
      improves the detection rate of cancer.

PMID- 12796648
TI  - Radical prostatectomy nomograms in black American men: accuracy and
      applicability.
AB  - PURPOSE: Nomograms have been developed to allow the prediction of disease
      recurrence based on clinical and pathological parameters in patients with
      clinically localized prostate cancer. However, they have been constructed using
      predominantly white American male (CAM) cohorts. We have previously shown that
      black American males (AAMs) have worse disease-free survival after radical
      prostatectomy after controlling for known prognostic factors. We tested the
      accuracy of prognostic nomograms in a population of AAMs with prostate cancer
      treated with radical prostatectomy. MATERIALS AND METHODS: We tested the
      performance of published preoperative and postoperative prognostic nomograms in a
      cohort of patients treated with radical prostatectomy as monotherapy for
      localized prostate cancer at Wayne State University in the prostate specific
      antigen era. Predictions made with the nomogram were stratified by race and
      compared with actual outcomes. The summary statistic used to evaluate the
      nomogram was the concordance index. A value of 0.5 indicates no predictive
      discrimination, whereas a value of 1.0 indicates perfect discrimination. RESULTS:
      A total of 1,043 patients, including 331 AAMs (32%) and 712 CAMs (68%), comprised
      the study cohort. Treatment failure was defined as increasing prostate specific
      antigen, which occurred in 193 patients (18.5%). The preoperative concordance
      index for CAMs and AAMs was 0.78 and 0.74, respectively (p = 0.8). The
      postoperative index was 0.85 and 0.83, respectively (p = 0.9). CONCLUSIONS:
      Preoperative and postoperative nomograms can be applied accurately to an
      individual regardless of race.

PMID- 12796649
TI  - The role of p53, bcl-2 and E-cadherin expression in predicting biochemical
      relapse for organ confined prostate cancer in Taiwan.
AB  - PURPOSE: We evaluated the prognostic significance of p53, bcl-2 and E-cadherin
      immunoreactivity for organ confined prostate cancer after radical prostatectomy.
      MATERIALS AND METHODS: The medical records on 70 pT2 prostatic adenocarcinomas
      were analyzed retrospectively. Radical prostatectomy specimens were stained using
      antip53 (DO7), antibcl-2 (124) (Dako, Glostrup, Denmark) and antiE-cadherin (HECD
      1) (R & D Systems, Abingdon, United Kingdom) antibodies. Biochemical relapse was
      defined as 2 consecutive elevations in serum prostatic specific antigen (PSA)
      higher than 0.2 ng/ml. The prognostic significance of Gleason grade, PSA, and
      p53, bcl-2 and E-cadherin expression was assessed. RESULTS: While p53
      immunoreactivity was identified in 16 patients (22.9%), only 3 tumors (4.3%)
      expressed bcl-2. Aberrant E-cadherin expression was noted in 39 tumors (55.7%).
      At a median followup of 36.5 months 21 patients (30%) experienced biochemical
      relapse. There was a significantly higher biochemical failure rate in patients
      with abnormal bcl-2 and E-cadherin expression (log rank test p = 0.024 and 0.003,
      respectively). On multivariate analysis bcl-2 and E-cadherin contributed
      independently to the prediction of PSA relapse (p = 0.017 and 0.005,
      respectively). CONCLUSIONS: We noted that bcl-2 and aberrant E-cadherin
      expression are independent factors predicting biochemical relapse in stage pT2
      prostatic cancers.

PMID- 12796650
TI  - Diagnosis and reconstruction of the dorsal or circumferential urethral
      diverticulum.
AB  - PURPOSE: Uncommonly a saddlebag urethral diverticulum (UD) may extend
      circumferentially around the urethra dorsally or anteriorly with compromise of
      the adjacent tissues. Excision of the entire mucosalized surface of this type of
      UD may leave an extensive gap in the urethra. Unfortunately the full extent of a
      saddlebag UD is often not appreciated on preoperative imaging and it is only
      discovered intraoperatively when potential reconstructive flaps have already been
      compromised. The advent of endoluminal magnetic resonance imaging (eMRI) has
      provided outstanding preoperative staging that has greatly aided in the
      successful reconstruction of the cases. We present our experience with the
      diagnosis and reconstruction of these complex UDs. MATERIALS AND METHODS: A
      review of 41 patients with UD at a single institution revealed 9 with
      circumferential involvement of the urethra confirmed on eMRI. All patients had
      voiding cystourethrography as the initial diagnostic modality. Four of the 9
      patients had had at least 1 prior attempt at surgical repair elsewhere.
      Presenting symptoms included severe pain in 7 of the 9 patients, recurrent
      cystitis in 7, a vaginal mass in 2 and mixed urinary incontinence in 6. Eight of
      the 9 patients had undergone attempted surgical repair. Surgical reconstruction
      consisted of complete division of the urethra to access the dorsal wall of the UD
      with partial urethrectomy. Urethral continuity was restored by end-to-end
      urethroplasty in 5 patients and by tubularizing the dorsal (anterior) wall of the
      UD to construct a neourethral segment in 3. A Martius flap and pubovaginal sling
      were used selectively. Postoperatively voiding cystourethrography was performed
      in all patients to document absence of the UD. Self-administered patient
      questionnaires were completed preoperatively and postoperatively. RESULTS: All
      patients report subjective relief of pain. Six of 8 patients did not use pads for
      incontinence. One patient used 2 to 3 pads daily for stress urinary incontinence
      symptoms and 1 had persistent urgency with rare incontinence, for which she used
      1 pad daily. Complications included a distal urethrovaginal fistula in 1 patient
      and urethral stricture in 1. CONCLUSIONS: Circumferential UD is an unusual
      problem. However, with the use of eMRI as a diagnostic and staging modality the
      incidence may be higher than previously realized. Preoperative knowledge of the
      extent of the UD is helpful in ensuring complete excision of the UD and
      optimizing urethral reconstruction. We conclude that excision and reconstruction
      of the circumferential UD is possible with excellent symptomatic and anatomical
      results.

PMID- 12796651
TI  - The problems of penile urethroplasty with particular reference to 2-stage
      reconstructions.
AB  - PURPOSE: We evaluate the anecdotal high revision rate of 2-stage urethroplasty.
      MATERIALS AND METHODS: The short-term revision rates after 1-stage (139 cases)
      and 2-stage (103) urethroplasties were compared. RESULTS: There were 4 revisions
      after 1-stage urethroplasty (4 of 139, 3%) and all involved the penile urethra
      (20%). The revision rate was 37.8% after stage 1 and 25.3% after stage 2 and of 2
      stage urethroplasty 85%, involved the penile urethra. CONCLUSIONS: Although 2
      stage has a significantly lower re-stricture rate than 1-stage urethroplasty for
      complex strictures in the penile urethra, it does so at the expense of a
      significantly higher revision rate particularly of the penile urethra.

PMID- 12796652
TI  - The long-term results of urethroplasty.
AB  - PURPOSE: We update our long-term data on the effectiveness of urethroplasty.
      MATERIALS AND METHODS: A total of 166 patients operated on before 1990 are
      currently under followup or lived at least 10 years after surgery. Anastomotic
      urethroplasty was performed in 82 patients and substitution urethroplasty in 84.
      RESULTS: The 5, 10 and 15-year re-stricture rates after anastomotic urethroplasty
      were 12%, 13% and 14%, respectively, and the complication rate was 7%. The 5, 10
      and 15-year re-stricture rates after substitution urethroplasty were 21%, 31% and
      58%, respectively, and the complication rate was 33%. CONCLUSIONS: The results of
      anastomotic urethroplasty are good and sustained in the long term, while the
      results of substitution urethroplasty deteriorate steadily with time and there is
      definite room for improvement. An anastomotic repair should be performed in
      preference to a substitution repair when possible.

PMID- 12796653
TI  - Editorial: The art of urethral reconstruction.

PMID- 12796654
TI  - Detection of medullary and papillary necrosis at an early stage by multiphasic
      helical computerized tomography.
AB  - PURPOSE: Multiphasic helical computerized tomography (CT) is advocated to
      identify early manifestations of papillary and medullary necrosis based on
      decreased enhancement of circumscribed areas in the medullary pyramid. At this
      stage the devascularizing process can be reversed if causative conditions such as
      infections or diabetes mellitus are effectively treated. MATERIALS AND METHODS:
      Multiphasic helical CTs were performed in 31 male and 26 female patients with
      complaints of microscopic hematuria (41), macroscopic hematuria (2), bacteriuria
      (39) and pyuria (9). Pre-enhancement, arterial, early corticomedullary,
      parenchymal and excretory phase helical CTs generated 1.25 to 5 mm. thick slices.
      Followup examination included multiphasic helical CT at 1 and 3 months, and
      excretory urography for some patients at 3 months. RESULTS: Bacteriuria was
      identified as the probable cause of medullary and papillary necrosis in 39
      patients, of whom 28 were treated with effective antibiotic therapy, resulting in
      normalization and re-perfusion of the initial lesion in 16, no change in 5 and
      progressive disease in 7 at 3-month followup. Of 8 lesions not treated with
      specific antibiotic therapy 4 progressed and 4 remained unchanged. CONCLUSIONS:
      Multiphasic helical CT unlike the excretory urogram can identify medullary and
      papillary necrosis at an early stage when effective treatment of the underlying
      cause can reverse the process of devascularization and prevent sloughing of
      medullary tissues.

PMID- 12796655
TI  - Ureteroscopy: effect of technology and technique on clinical practice.
AB  - PURPOSE: Technical advances in ureteroscopy allow for more aggressive management
      of upper tract pathology. We evaluate to what extent clinical practice and
      treatment efficacy have been impacted by improvements in technology and
      technique. MATERIALS AND METHODS: In 1998, 176 consecutive patients underwent 182
      ureteroscopic procedures at our institution. Retrospective chart review was
      performed. Factors such as clinical indication, pathology location, type of
      ureteroscope, procedure duration, procedure success, complication rate and length
      of stay were evaluated. Data from the 1998 cohort were compared to those obtained
      from a cohort of patients from 1992. Statistical analysis was performed using chi
      square test. RESULTS: Overall stone extraction rate was 94.4% (1992) vs 88.5%
      (1998) (p = 0.05). Proximal stones were treated in 13.5% (1998) vs 28.3% (1998)
      of cases. Distal stone extraction rate was 97.2% (1992) vs 95.1% (1998) (p =
      0.43) and proximal stone extraction rate was 76.5% (1992) vs 71.9% (1998) (p =
      0.73). Diagnostic inspection success rate was 98.3% (1992) vs 98.3% (1998). Use
      of flexible ureteroscopy was 11.5% (1992) vs 29.4% (1998). Complication rate was
      12% (1992) vs 10.2% (1998) (p = 0.76). Of the cases 76.1% were outpatient in 1998
      vs only 50% in 1992. CONCLUSIONS: Recent advances in ureteroscopic technology
      permit more aggressive instrumentation of the upper tract as reflected in higher
      use of flexible ureteroscopy and more frequent attempts to manage proximal
      ureteral calculi. These advances have not translated into better efficacy of
      calculus treatment. Furthermore, our data reflect a nationwide trend toward
      outpatient treatment.

PMID- 12796656
TI  - Identifying patients who are suitable for stentless ureteroscopy following
      treatment of urolithiasis.
AB  - PURPOSE: Foregoing ureteral stents following ureteroscopy for urinary calculi is
      an evolving practice. Randomized trials support stent omission in select cases
      though generalizability is unclear and criteria for stentless ureteroscopy are
      unknown. Therefore, we sought to identify significant clinical characteristics
      affecting postoperative morbidity in unstented patients to provide a context for
      future randomized trials. MATERIALS AND METHODS: Of 837 ureteroscopic procedures
      for urolithiasis performed at our institution from January 1997 through January
      2002 a ureteral stent was not placed in 226 (32%). Among these patients 47 had no
      stone at the time of the procedure leaving 219 (26%) who were treated for urinary
      calculus disease. Multivariate logistic regression was used to determine the
      association of 24 variables with postoperative morbidity. RESULTS: Of the 219
      patients treated with ureteroscopy 39 (18%) had a postoperative complication,
      which was obstructive in 26 (12%), infectious in 10 (5%), and related to patient
      co-morbidity in 3 (1%). Factors associated with postoperative morbidity included
      renal pelvic location (p = 0.02), lithotripsy (p = 0.03), bilateral procedure (p
      = 0.07), history of urolithiasis (p <0.0001), diabetes mellitus (p = 0.06),
      recent/recurrent infection (p <0.0001), operative time 45 minutes or greater (p =
      0.07), operative time 45 minutes or greater plus lithotripsy (p = 0.0004),
      operative time 45 minutes or greater plus ureteral dilation (p = 0.07) and
      bilateral stentless procedure (p = 0.005). CONCLUSIONS: Multiple patient and
      operative factors may predispose a patient to postoperative morbidity after a
      stentless procedure. Future trials should prospectively validate the role of
      these factors in either promoting (e.g., history of urolithiasis) or preventing
      (e.g., preoperative stent) a postoperative complication in the setting of
      stentless ureteroscopy.

PMID- 12796657
TI  - Retrograde ureteroscopy in patients with orthotopic ileal neobladder urinary
      diversion.
AB  - PURPOSE: We assess the feasibility, technique, complications and clinical
      outcomes of retrograde ureteroscopy in patients with orthotopic ileal neobladder.
      MATERIALS AND METHODS: We retrospectively reviewed our ureteroscopy experience to
      identify procedures performed in patients who had previously undergone cystectomy
      with orthotopic ileal neobladder urinary diversion. These procedures were
      reviewed and data collected regarding patient characteristics, indication for
      endoscopic evaluation, surgical technique, findings, complications and followup.
      RESULTS: Eight patients with neobladder diversion were taken for 9 sessions in
      the cystoscopy suite for attempted retrograde ureteroscopy on 13 renal units. The
      indication for ureteroscopy was an upper tract filling defect, positive cytology
      or calculi. The ureter and renal pelvis were successfully accessed and visualized
      in 10 of 13 renal units. The cause of failure in the 3 unsuccessful procedures
      was inability to access the ureteral orifice. Mean operative time +/- SD was 78
      +/- 34 minutes. Urothelial abnormalities were identified in 4 patients, extrinsic
      compression in 2 and stones in 3. In 1 patient postoperative hematuria developed,
      which spontaneously resolved. Fluoroscopy was essential to identify the afferent
      limb of the reservoir, and a directional guide wire was helpful in engaging the
      ureteral orifice. CONCLUSIONS: Ureteroscopic evaluation and treatment of upper
      tract abnormalities are feasible and practical in most patients with orthotopic
      neobladder urinary diversion. Identification of the ureteral orifice is
      challenging but can be accomplished with a combination of endoscopic and
      fluoroscopic techniques. This procedure avoids the morbidity of percutaneous
      access, and complications are minimal.

PMID- 12796658
TI  - Editorial: Ureteroscopy continues to evolve.

PMID- 12796659
TI  - A pelvic drain may be avoided after radical retropubic prostatectomy.
AB  - PURPOSE: We reassessed the role of routine pelvic cavity drainage to prevent
      complications after radical retropubic prostatectomy (RRP). MATERIALS AND
      METHODS: RRP was performed in 116 consecutive patients with clinically localized
      adenocarcinoma of the prostate. Clinical and pathological information was
      recorded for each patient. After the prostate was removed and the anastomotic
      sutures were tied the bladder was filled with saline through the urethral
      catheter. If there was no significant leakage, a drain was not placed. RESULTS:
      We did not place a drain in 85 of the 116 patients (73%). There were 3 immediate
      postoperative complications. In a patient without a drain, a urinoma developed
      that required percutaneous placement of a drain on postoperative day 2. None of
      the 116 patients had clinical evidence of infection, lymphocele or hematoma. Two
      patients had hematuria 2 weeks after catheter removal and needed bladder
      irrigation. Neither patient had a drain. Three patients (drain and no drain in 1
      each) were in urinary retention after catheter removal, which required catheter
      reinsertion for an additional week. None had an anastomotic stricture.
      CONCLUSIONS: The morbidity of RRP is low when performed by those who regularly
      perform this procedure. If the bladder neck is preserved or meticulously
      reconstructed, there may be little or no extravasation and, thus, routine
      drainage may be unnecessary. In properly selected cases morbidity is not
      increased by omitting a drain from the pelvic cavity after RRP.

PMID- 12796660
TI  - Simple perineal prostatectomy: lessons learned from a modern series.
AB  - PURPOSE: Experience with simple perineal prostatectomy has not been well
      described in the recent literature. We describe our operative technique and
      compare objective demographic, preoperative, intraoperative and postoperative
      parameters in patients undergoing open prostatectomy for benign prostatic
      hyperplasia via 3 routes, namely perineal, retropubic, and suprapubic. MATERIALS
      AND METHODS: We retrospectively reviewed all cases of open prostatectomy at
      Veterans Affairs Medical Center, San Diego between August 2001 and September
      2002. A total of 22 patients were identified. Objective parameters were recorded
      and compared, including patient age, history of urinary retention, ultrasound
      volume, prostate specific antigen, patient and specimen weight, operative time,
      estimated blood loss, transfusion requirement, days of hospitalization and
      postoperative analgesic requirement. RESULTS: In the 22 patients who underwent
      open prostatectomy the operative approach was perineal in 6, retropubic in 8 and
      suprapubic in 8. Operative time and hospital stay were significantly less in the
      perineal prostatectomy group. CONCLUSIONS: Simple perineal prostatectomy is a
      viable alternative for most patients considered candidates for open prostatectomy
      and it is our preferred approach for obese patients. With perineal prostatectomy
      patients may expect shorter hospitalization and less analgesic requirement but
      likely require a longer period of catheter drainage.

PMID- 12796661
TI  - Risk of elevated creatine kinase and myoglobulinemia due to incised muscles in
      patients who underwent urological surgery.
AB  - PURPOSE: We clarified the risk of elevated creatine kinase (CK) and
      myoglobulinemia during incised muscle urological operations. MATERIALS AND
      METHODS: We retrospectively reviewed 58 consecutive cases of radical nephrectomy
      with muscle incision and 89 consecutive radical prostatectomies or radical
      cystectomies without muscle incision. Operations with or without muscle incision
      were divided into 2 groups depending on operative time (200 minutes or less and
      201 to 400). Increases in CK and myoglobin were compared between the 2 groups,
      and between muscle incision and no muscle incision at each operative time.
      RESULTS: CK and myoglobin were proportionally increased according to operative
      time in operations without muscle incision but not in muscle incision operations,
      in which high CK and myoglobin were seen even with short operative times. CK and
      myoglobin were more increased in muscle incision operations than in those without
      incision with significance at each operative time. However, maximum CK and
      myoglobin were 2,220 IU/L and 3,600 ng/ml, respectively, in muscle incision
      operations. CONCLUSIONS: Even with short operative times surgeries with muscle
      incision are associated with a marked increase in CK and myoglobulinemia.
      However, CK and myoglobin are not sufficiently high for rhabdomyolysis with acute
      renal failure to develop.

PMID- 12796662
TI  - Urodynamic patterns following ischemic spinal cord events.
AB  - PURPOSE: The nature of bladder function following ischemic injuries to the spinal
      cord (vSCI) is poorly understood. We describe urodynamic (UD) findings in
      patients with vSCI and determined the optimal management of voiding dysfunction.
      MATERIALS AND METHODS: From January 1997 through September 2001, 18 patients were
      diagnosed with vSCI. All underwent neurological and urodynamic evaluation. The
      etiology of vSCI was abdominal aortic aneurysm repair in 10 patients, another
      surgical procedure in 4 and a spontaneous spinal cord infarct in 2. RESULTS: Two
      patients (American Spinal Injury Association [ASIA] class A) had detrusor
      areflexia or hyporeflexia and performed clean intermittent catheterization. Of
      the 10 patients assigned to ASIA class C 50% had UD evidence of abnormal
      compliance, unstable detrusor contractions and detrusor-external sphincter
      dyssynergia (DESD). All 10 patients had thoracic or cervical sensory levels and
      60% had detrusor hyporeflexia or areflexia. A single patient voided
      spontaneously, while the remainder performed continuous or intermittent
      catheterization. Five patients assigned to ASIA class D had no abnormal
      compliance, unstable detrusor contractions or DESD. Four patients voided
      spontaneously or by abdominal straining. The patients with a history of abdominal
      aortic aneurysm repair were a heterogeneous population. CONCLUSIONS: While the
      etiology or sensory level of vSCI does not appear to predict UD patterns with
      consistency, greater preservation of motor function may be associated with
      improved parameters. All patients with vSCI and lower urinary tract symptoms
      require thorough UD evaluation and ongoing surveillance is mandated because
      deterioration may develop with time. Clean intermittent catheterization may
      represent the most effective method of bladder emptying for patients unable to
      void voluntarily. However, early evidence of abnormal compliance and DESD has
      also been seen in these patients, underscoring the need for close UD
      surveillance.

PMID- 12796663
TI  - A catheter based method to activate urethral sensory nerve fibers.
AB  - PURPOSE: The ability to control bladder activity would provide a valuable tool to
      assist individuals with neurological disorders or spinal cord injury (SCI).
      Recent studies in animal models have shown that bladder contractions can be
      evoked by electrical stimulation of urethral afferent nerves. We developed and
      validated in cats a minimally invasive method to stimulate electrically the
      sensory nerve fibers that innervate the urethra. MATERIALS AND METHODS: The
      urethra was stimulated electrically along its length via a catheter mounted
      circumferential electrode in 6 cats. The urethra was similarly stimulated in a
      male individual with complete SCI. RESULTS: Robust bladder contractions were
      generated via intraurethral electrical stimulation in all cat experiments. Peak
      responses were obtained in the proximal and prostatic urethra. In the individual
      with SCI bladder contractions were generated via intraurethral stimulation at a
      position 4 cm distal to the bladder. Responses in cats and the human depended on
      bladder volume. CONCLUSIONS: To our knowledge this study provides the first
      documentation of generating bladder contractions via intraurethral electrical
      stimulation in cats and humans. This method provides a research tool for future
      studies to investigate these pathways in humans. Preliminary human results
      suggest that urethral afferent mediated neural pathways demonstrated in animal
      models exist in humans and support the development of neural prostheses using
      electrical stimulation of these nerves to restore control of bladder function in
      individuals with neurological disorders or SCI.

PMID- 12796664
TI  - The role of pelvic floor exercises on post-prostatectomy incontinence.
AB  - PURPOSE: Post-radical prostatectomy incontinence occurs in 0.5% to 87% of
      patients. This condition may be attributable to intrinsic sphincteric deficiency,
      and/or detrusor abnormalities. Previous studies of pelvic floor exercise (PFE)
      for improving post-prostatectomy incontinence have shown mixed results. We
      determined whether preoperative and early postoperative biofeedback enhanced PFE
      with a dedicated physical therapist would improve the early return of urinary
      incontinence. MATERIALS AND METHODS: A total of 38 consecutive patients
      undergoing radical prostatectomy from November 1998 to June 1999 were randomly
      assigned to a control or a treatment group. The treatment group of 19 patients
      was referred to physical therapy and underwent PFE sessions before and after
      surgery. Patients were also given instructions to continue PFE at home twice
      daily after surgery. The control group of 19 men underwent surgery without formal
      PFE instructions. All patients completed postoperative urinary incontinence
      questionnaires at 6, 12, 16, 20, 28 and 52 weeks. Incontinence was measured by
      the number of pads used with 0 or 1 daily defined as continence. RESULTS: Overall
      66% of the patients were continent at 16 weeks. A greater fraction of the
      treatment group regained urinary continence earlier compared with the control
      group at 12 weeks (p <0.05). Three control and 2 treatment group patients had
      severe incontinence (greater than 3 pads daily) at 16 and 52 weeks. Of all
      patients 82% regained continence by 52 weeks. CONCLUSIONS: PFE therapy instituted
      prior to radical prostatectomy aids in the earlier achievement of urinary
      incontinence. However, PFE has limited benefit in patients with severe urinary
      incontinence 16 weeks after surgery. There is a minimal long-term benefit of PFE
      training since continence rates at 1 year were similar in the 2 groups.

PMID- 12796665
TI  - Urethral erosion after synthetic and nonsynthetic pubovaginal slings: differences
      in management and continence outcome.
AB  - PURPOSE: We present a series of urethral erosion following a pubovaginal sling
      procedure due to synthetic and nonsynthetic materials and discuss their
      management and continence outcome. MATERIALS AND METHODS: During a 3-year period
      57 patients underwent urethrolysis for urethral obstruction after receiving a
      pubovaginal sling. Urethral erosion, defined as sling material entering the
      urethral lumen, was present in 9 patients and this cohort comprises the focus of
      our review. In 3 patients the eroded material was synthetic, that is ProteGen
      (Boston Scientific, Natick, Massachusetts) in 2 and polypropylene in 1. This
      condition was treated with removal of the whole sling, multilayer closure of the
      erosion and selective use of a Martius flap. In 6 patients the eroded material
      was nonsynthetic, that is allograft fascia in 5 and autograft fascia in 1. This
      condition was treated with sling incision and multilayer closure of the urethra.
      Preoperative assessment included a urogynecologic questionnaire, measurement of
      pad use, a voiding diary, cystourethroscopy and videourodynamics. Postoperatively
      similar parameters were used to assess continence outcomes and the need for
      subsequent procedures. RESULTS: Nine patients were followed 30 months after
      urethrolysis. All 9 women had some manifestation of voiding dysfunction following
      the pubovaginal sling procedure, including urinary retention in 4, urge
      incontinence in 3 and mixed incontinence in 2. Urinary retention resolved in 3
      patients and urge incontinence resolved in 4. Stress urinary incontinence (SUI)
      persisted in 2 of the 3 patients in the synthetic group, while no patient in the
      nonsynthetic group had recurrent SUI. There were no recurrent urethral erosions
      or fistulas in either group. CONCLUSIONS: Urethral erosion after a pubovaginal
      sling procedure can occur irrespective of the sling material. However, recurrent
      SUI is not an invariable outcome of the management of urethral erosion following
      the pubovaginal sling procedure.

PMID- 12796666
TI  - Magnetic resonance imaging anatomy of the female genitalia in premenopausal and
      postmenopausal women.
AB  - PURPOSE: We used contrast enhanced magnetic resonance imaging (MRI) of the female
      genital organs to describe normal anatomy and differences between premenopausal
      and postmenopausal women. MATERIALS AND METHODS: A total of 12 healthy
      premenopausal and 9 healthy postmenopausal women underwent MRI. A 1.5 Tesla
      system with phased array coils anterior and posterior to the pelvis was used to
      produce T1-weighted images before and after intravenous administration of MS-325
      (Epix Medical, Cambridge, Massachusetts), a new gadolinium based blood pool
      contrast agent. Select structural dimensions were measured for reference.
      RESULTS: The clitoris and vestibular bulbs were well delineated on T1-weighted
      post-contrast images. The clitoral unit formed a brightly enhancing, wishbone
      shaped structure lying just anterior to the inverted V of the bulbs, which
      surrounded the urethra and vagina. The urethral complex had a target-like
      appearance with layers that were discernible on T1 post-contrast images. The
      urethra, vagina and rectum formed a distinct complex within uniformly enhancing
      soft tissue. The vagina was well visualized in premenopausal subjects but without
      distinguishable mucosal rugae or clearly separate layers in postmenopausal
      subjects. Postmenopausal subjects were also observed to have smaller labia minora
      width, vestibular bulb width, vaginal width and wall thickness, and cervical
      diameter. Pelvic and genital structures were not well visualized on T1
      noncontrast images. CONCLUSIONS: To our knowledge we describe detailed female
      genital anatomy for the first time using MRI with MS-325 contrast medium. The
      clitoris, vestibular bulbs, labia majora and minora, urethra, vagina, cervix and
      rectum are well visualized on T1 post-contrast images. The observed genital
      anatomy on MRI was consistent with descriptions in current anatomical texts.
      Differences in the female genitalia between premenopausal and postmenopausal
      women were discernible on MRI. These data are important for future studies using
      MRI for evaluating anatomical anomalies, postoperative changes and female sexual
      function.

PMID- 12796667
TI  - Changes in nocturia from medical treatment of benign prostatic hyperplasia:
      secondary analysis of the Department of Veterans Affairs Cooperative Study Trial.
AB  - PURPOSE: We evaluate the efficacy of medical therapy on nocturia in men with
      benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a
      secondary analysis of data from the VA Cooperative Study Program Trial in which
      1,229 men with BPH 45 to 80 years old were randomly assigned to receive
      terazosin, finasteride, combination or placebo. RESULTS: The 1,078 men who
      completed 12 months of the trial are included in this study. Of those men 1,040
      (96.5%) had at least 1 episode of nocturia at baseline and 38 (3.5%) had less
      than 1 episode (baseline nocturia is an average of 2 measures). Of those 1,040
      men 788 (75.8%) had 2 or more nocturia episodes. Overall, nocturia decreased from
      a baseline mean of 2.5 to 1.8, 2.1, 2.0 and 2.1 episodes in the terazosin,
      finasteride, combination and placebo groups, respectively. Of men with 2 or more
      episodes of nocturia 50% reduction in nocturia was seen in 39%, 25%, 32% and 22%
      in the terazosin, finasteride, combination and placebo groups, respectively.
      Changes in nocturia were correlated with changes in reported bother from nocturia
      (Pearson correlation 0.48), BPH impact index (0.32) and overall satisfaction with
      urinary symptoms (0.33). CONCLUSIONS: Terazosin and combination therapy reduced
      nocturia in men with BPH, yet the net advantage of terazosin over placebo was a
      net reduction of 0.3 nocturia episode. For a person to reach a 50% or greater
      reduction in nocturia, the advantage of terazosin over placebo was 17 percentage
      points. Changes in nocturia had a moderate impact on symptom specific quality of
      life measures.

PMID- 12796668
TI  - Holmium laser enucleation of prostate (HoLEP): the Methodist Hospital experience
      with greater than 75 gram enucleations.
AB  - PURPOSE: Holmium laser enucleation of the prostate (HoLEP) effectively removes
      obstructive prostate tissue in minimally invasive fashion. We present our large
      enucleation outcomes (greater than 75 gm retrieved). We examined post-procedural
      prostate specific antigen (PSA) and transrectal ultrasound (TRUS) volume changes
      to assess tissue removal completeness. MATERIALS AND METHODS: We retrospectively
      reviewed HoLEPs performed from April 1, 1999 through September 30, 2002 to
      identify all enucleations greater than 75 gm. Demographic, laboratory, operative
      and pathological data were obtained. Patients were surveyed to document longer
      term complications. RESULTS: The cohort of 108 patients had a mean age and
      specimen weight of 71.5 years (range 53 to 90) and 120.6 gm (range 75.3 to 376),
      respectively. Average procedural time and hospital stay were 166.8 minutes (range
      75 to 473) and 1.2 days (range 0 to 4), respectively. No deaths or episodes of
      transurethral resection syndrome occurred. Postoperative complications included
      transfusion in 2 cases, a clot retention episode in 3, capsular perforation in 2,
      morcellator blade malfunction in 4, minor bladder mucosal injury in 1 and bladder
      neck contracture in 1. American Urological Association symptom scores reassessed
      in 53 patients without chronic retention an average +/- SD of 10.6 +/- 7.1 months
      postoperatively showed a mean decrease from 20.3 +/- 6.4 to 4.7 +/- 3.8. PSA in
      48 patients a mean of 5.0 +/- 4.1 months postoperatively had decreased an average
      of 91.7%. In 10 patients TRUS data revealed a mean post-procedural volume
      decrease of 85.9%. CONCLUSIONS: HoLEP can be performed on extremely large
      prostates with minimal risk or need for secondary interventions. Most patients
      are discharged home after an overnight stay. Postoperative decreases in PSA and
      TRUS volumes support the completeness of enucleation that can be achieved.

PMID- 12796669
TI  - Identification of communicating branches among the dorsal, perineal and cavernous
      nerves of the penis.
AB  - PURPOSE: The mechanism of human erection requires the coordination of an intact
      neuronal system that includes the cavernous, perineal, and dorsal nerves of the
      penis. We defined the communication of these 3 nerves that travel under the pubic
      arch using specific neuronal immunohistochemical staining and 3-dimensional
      reconstruction imaging technique. MATERIALS AND METHODS: A total of 18 normal
      human fetal penile specimens at 17.5 to 32 weeks of gestation were studied by
      immunohistochemical techniques. Serial sections were stained with antibodies
      raised against the neuronal markers S-100, and neuronal nitric oxide synthase
      (nNOS), vesicular acetylcholine transporter (VAChT), calcitonin gene-related
      peptide and substance P. RESULTS: The continuation of the dorsal neurovascular
      bundle of the prostate was documented under the pubic arch. Two distinct nerve
      bundles were identified superior to the urethra and medial to the origin of the
      crural bodies. Nerve bundles were observed to join the corporeal bodies at the
      penile hilum. Proximal to the penile hilum the dorsal nerves stained only for S
      100 and VAChT. From the junction of the crural bodies at the hilum to the glans
      penis dorsal nerve fibers stained positive for S-100, VAChT and nNOS. Calcitonin
      gene-related peptide and substance P demonstrated positive staining at the distal
      nerves, particularly at the glans. In contrast, the whole course of the cavernous
      nerve stained for S-100 and nNOS. Under the pubic arch at the penile hilum the
      cavernous nerves were found to convey nNOS positive branches to the dorsal nerve
      to transform its immunoreactivity to nNOS positive. Proximal nNOS negative
      perineal nerves were shown to stain positive for nNOS distal on the penis.
      Interaction between nNOS positive dorsal nerve branches and perineal nerves was
      at the cavernous-spongiosal junction, where the bulbospongiosus muscle
      terminates. CONCLUSIONS: At penile hilum, where the corporeal bodies start to
      separate, the cavernous nerve sends nNOS positive fibers to join the dorsal nerve
      of the penis, thereby, changing the functional characteristics of the distal
      penile dorsal nerve. Similarly the nNOS negative, ventrally located perineal
      nerve originating from the pudendal nerve becomes nNOS reactive at the cavernous
      spongiosal junction. These 2 examples of redundant neuronal wiring in the penis
      may impact erectile function, especially during reconstructive surgery.

PMID- 12796670
TI  - Comparison of satisfaction rates and erectile function in patients treated with
      sildenafil, intracavernous prostaglandin E1 and penile implant surgery for
      erectile dysfunction in urology practice.
AB  - PURPOSE: We compared erectile function status and satisfaction rates in patients
      who received treatment for erectile dysfunction (ED) with sildenafil,
      intracavernous prostaglandin E1 (ICI) and penile implant surgery (IPP). MATERIALS
      AND METHODS: A total of 138 consecutive patients who received treatment for ED
      between April 2000 and April 2001 were considered candidates for study. Mean
      followup was 19.54 months. Of the patients 27 were not available for followup and
      26 were not on any form of treatment. Of the patients receiving treatment for ED
      85 were administered the Erectile Dysfunction Inventory for Treatment
      Satisfaction (EDITS) questionnaire and the Erectile Function Domain (EFD) of the
      International Index of Erectile Function questionnaire. Three treatment groups
      were identified, including 31 patients on sildenafil citrate, 22 on ICI and 32
      who underwent IPP. Mean total EDITS, EDITS Index and EFD scores in the 3 groups
      were considered for statistical evaluation. RESULTS: There was no statistical
      difference in the total EDITS (25.59 versus 27.06, p = 0.48), EDITS Index (58.16
      versus 61.15, p = 0.49) or EFD (22.91 versus 20.26, p = 0.12) score between the
      groups on ICI and sildenafil citrate, respectively. Total EDITS, EDITS Index and
      EFD scores were significantly higher in patients who underwent IPP than those on
      sildenafil citrate (36.09 versus 27.06, p <0.001, 82.03 versus 61.51, p <0.001
      and 27.88 versus 20.26, p <0.001, respectively). Total EDITS, EDITS Index and EFD
      scores were significantly higher in patients who underwent IPP than those on ICI
      (36.09 versus 25.59, 82.03 versus 58.16 and 27.88 versus 22.91, respectively, all
      p <0.001). CONCLUSIONS: At a mean followup of 19.54 months patients who underwent
      penile implant surgery had significantly better erectile function and treatment
      satisfaction than those receiving sildenafil citrate and intracavernous
      prostaglandin E1.

PMID- 12796671
TI  - Comparison of the efficacy and safety of 90 mg versus 20 mg fluoxetine in the
      treatment of premature ejaculation.
AB  - PURPOSE: We compare the efficacy and side effects of 90 mg fluoxetine once weekly
      versus 20 mg fluoxetine as single oral therapy for patients complaining of
      premature ejaculation without evident organic causes. MATERIALS AND METHODS: The
      study comprised 80 patients with a mean age of 36 years with premature
      ejaculation who presented to the urology clinic of 3 hospitals in Barcelona.
      Pretreatment evaluation included history and physical examination, International
      Index of Erectile Function (IIEF), Meares-Stamey test and ejaculatory latency
      time evaluation. The patients were randomized into treatment groups receiving 1
      capsule of 90 mg fluoxetine a week (group 1) and 1 capsule of 20 mg fluoxetine a
      day (group 2) for 3 months. The 4-month followup included: ejaculatory latency
      time measurement, IIEF and partner sexual satisfaction. RESULTS: Mean
      pretreatment ejaculatory latency times for groups 1 and 2 were 0.48 minute (range
      0 to 2.10) and 0.50 minute (0 to 2.04), respectively. After 3 months of treatment
      of weekly and daily administration of fluoxetine mean ejaculatory latency time
      was 3.57 and 3.37 minutes, respectively (p >0.01). Partner sexual satisfaction
      and IIEF rate were greater with 90 mg fluoxetine but no statistical difference
      was found. Nausea, insomnia and headache were reported side effects but no
      significant difference was noted between 90 and 20 mg fluoxetine. CONCLUSIONS: In
      men with premature ejaculation 90 mg fluoxetine weekly may be regarded as an
      effective and safe treatment.

PMID- 12796672
TI  - Clinical, demographic and psychosocial correlates of complementary and
      alternative medicine use by men diagnosed with localized prostate cancer.
AB  - PURPOSE: We examined complementary and alternative medicine (CAM) use among men
      who received standard therapy for localized prostate cancer. MATERIALS AND
      METHODS: A total of 417 men completed a questionnaire 6 months after their
      treatment decision assessing clinical and psychosocial variables and use of 41
      available CAM therapies grouped into the 2 general categories of herbal/dietary
      and nonherbal (i.e. mind-body, bioelectromagnetic, traditional/folk medicine,
      pharmacological/biological). RESULTS: The prostate cancer diagnosis prompted 19%
      of our sample to start using some form of CAM for prostate health, and 67% of men
      reported having used some form of CAM for prostate health before being diagnosed.
      Initiation of CAM was associated with being a member of an ethnic minority group
      and a higher level of education. Initiation of nonherbal CAM was associated with
      being married, while use of herbal CAM therapies was significantly associated
      with choosing observation. Herbal use before diagnosis was associated with being
      white, higher level of education and being single. Prostate specific antigen at
      diagnosis, Gleason score, quality of life, participant perceptions of seriousness
      of prostate cancer or self-reported worry about prostate cancer were not related
      to initiation or prior use. Of those men reporting current use almost 50% did not
      inform their treating physician of using CAM therapies. CONCLUSIONS: Initiation
      of CAM therapies as a result of a prostate cancer diagnosis was fairly low,
      although two-thirds of men had used it before diagnosis. Half of the patients did
      not inform their physicians about such use and physicians should continue to
      probe patients about CAM use.

PMID- 12796673
TI  - Radical endoscopic assisted perineal prostatectomy.
AB  - PURPOSE: During radical perineal prostatectomy transection of the bladder neck
      and dissection of the seminal vesicles under direct vision can be difficult. We
      describe a technique of radical endoscopic assisted perineal prostatectomy that
      facilitates dissection of these structures. MATERIALS AND METHODS: Cadaveric
      dissections were performed in 4 individuals to develop and assess the technique.
      It was subsequently applied to a 64-year-old male with clinically localized
      prostate cancer (Gleason grade 3+3). Management of the bladder neck and seminal
      vesicles was performed with a bipolar transurethral resectoscope. The remainder
      of the procedure was performed via a traditional subsphincteric perineal approach
      with the patient in the standard dorsal lithotomy position. RESULTS: The bladder
      neck and seminal vesicles were successfully dissected in 55 minutes. Total
      operative time was 3 hours. Estimated blood loss was 500 cc. The patient was
      discharged home the morning of postoperative day 1 and the catheter was removed
      in the clinic on postoperative day 7. The final pathology report showed organ
      confined prostate cancer (Gleason 3+3). CONCLUSIONS: Radical endoscopic assisted
      perineal prostatectomy allows precise dissection of the bladder neck and seminal
      vesicles under direct vision. Accomplishing this dissection as the initial step
      of the procedure mobilizes the prostate, facilitating excision, and obviates the
      need for the extreme lithotomy position.

PMID- 12796674
TI  - Novel technique of Vest suture vesicourethral anastomosis in morbidly obese
      patient undergoing radical retropubic prostatectomy.
AB  - PURPOSE: The urethrovesical anastomosis can be a technically challenging
      procedure in the morbidly obese patient. We successfully overcame this challenge
      using a Vest suture technique. MATERIALS AND METHODS: After the completion of
      radical prostatectomy a Stamey needle is passed through the perineum under
      bimanual control. Vest sutures are placed and tied with a Foley catheter in
      place. RESULTS: This technique was used in a morbidly obese patient.
      Postoperatively continence was excellent. CONCLUSIONS: In the morbidly obese
      patient this novel technique of Vest suture placement should be considered to
      facilitate urethrovesical anastomosis after the completion of radical
      prostatectomy.

PMID- 12796675
TI  - Horseshoe kidney with pyelic fusion and crossed single ureter.

PMID- 12796676
TI  - Xanthogranulomatous adrenalitis.

PMID- 12796678
TI  - Sweet's syndrome associated with squamous cell carcinoma of the bladder.

PMID- 12796677
TI  - Spontaneous regression of pulmonary metastases from renal cell carcinoma after
      radio frequency ablation of primary tumor: an in situ tumor vaccine?

PMID- 12796679
TI  - Primitive neuroectodermal tumor of the prostate.

PMID- 12796680
TI  - Colourachal fistula in an adult presenting with feculent umbilical drainage.

PMID- 12796681
TI  - Pyoderma gangrenosum of penis.

PMID- 12796682
TI  - Segmental testicular infarction.

PMID- 12796683
TI  - Research enterprise in urology: a message to the urology leadership.

PMID- 12796684
TI  - Re: Risk factors for the formation of a steinstrasse after extracorporeal shock
      wave lithotripsy: a statistical model.

PMID- 12796685
TI  - Re: Comparison of contrast enhanced color Doppler targeted biopsy with
      conventional systematic biopsy: impact on prostate cancer detection.

PMID- 12796686
TI  - Re: Use of a colon based tubularized flap for an antegrade continence enema.

PMID- 12796687
TI  - Re: Skin graft for 2-stage treatment of severe hypospadias: back to the future?

PMID- 12796688
TI  - Treatment of daytime urinary incontinence in children: a systematic review of
      randomized controlled trials.
AB  - PURPOSE: We sought to determine the benefits and harms of interventions for
      children with daytime urinary incontinence. MATERIALS AND METHODS: Trials of any
      interventions for children with primary daytime incontinence (the urge syndrome
      and/or dysfunctional voiding) were identified from the Cochrane Controlled Trials
      Register, MEDLINE, EMBASE, reference lists of articles, abstracts from conference
      proceedings and contact with known experts in the field. Once identified, trial
      quality was assessed, data were extracted and results were expressed in terms of
      relative risks (RR) with 95% confidence intervals (CI) for individual trials, and
      summary estimates were obtained using a random effects model. All steps were done
      by 2 independent reviewers. RESULTS: Randomized trials of terodiline (2 studies),
      daytime alarms (1), imipramine (1) and biofeedback/oxybutynin (1) involving 383
      children were reviewed. No intervention was demonstrated to be effective. In the
      latter trial, which was the only one to evaluate a currently used intervention,
      after 9 months of treatment there was no difference in the proportions of
      children with unimproved daytime wetting with oxybutynin (RR 0.74, CI 0.26 to
      2.13) and biofeedback (0.92, 0.59 to 1.43) compared with placebo. CONCLUSIONS: No
      intervention tested in a trial to date has been proved to be of benefit to
      children with daytime urinary incontinence.

PMID- 12796689
TI  - Pediatric renal pelvic fullness: an ultrasonographic dilemma.
AB  - PURPOSE: We conducted a prospective study to define normal renal pelvic size in
      children. MATERIALS AND METHODS: Institutional Review Board approved consent was
      obtained to perform renal ultrasound during excretory urography (IVP) scheduled
      for medical management. Mean patient age (17 females, 11 males) was 5.2 years.
      Renal ultrasound was conducted concurrent with 10-minute IVP. RESULTS: Fifty
      kidneys were imaged with 51 collecting systems. IVP defined 44 collecting systems
      as normal. Mean anteroposterior pelvic diameter on sonography for these 44
      systems was 3.3 mm. One normal collecting system on IVP had a diameter greater
      than 10 mm on ultrasound (14 mm). No sonographic caliceal dilatation was seen in
      any kidney appearing normal on IVP. The 7 dilated systems on IVP had a mean
      ultrasound diameter of 17.1 mm. Two dilated collecting systems smaller than 10 mm
      in diameter on sonography had caliceal distention on ultrasound. CONCLUSIONS:
      Normal renal pelvis threshold diameter was 10 mm in asymptomatic children. We
      recommend further evaluation in children with caliceal dilatation and/or
      dilatation of the anteroposterior renal pelvis greater than 10 mm. Using these
      criteria, no system appearing abnormal on IVP would have been missed.

PMID- 12796690
TI  - A modified access technique for retroperitoneoscopic renal surgery in children.
AB  - PURPOSE: Present techniques for retroperitoneal endoscopic (RPE) access in
      children mimic those in adults but often result in peritoneal entry or gas leaks,
      both of which lead to a decrease in the retroperitoneal space. We describe a
      modification to the access technique that obviates these problems, thus,
      facilitating RPE in children. MATERIALS AND METHODS: In the lateral decubitus
      position the initial port is placed immediately lateral to the paraspinal
      muscles, similar to open dorsal lumbotomy fascial incision. A 5 mm skin incision
      is made at the level of the costovertebral angle and an artery forceps used to
      tunnel bluntly past the lumbodorsal fascia. A 5 mm port is placed with a blunt
      trocar, and expansion of the retroperitoneal space performed with the telescope
      and gas insufflation. Ancillary ports are placed and the telescope then moved to
      an anterior subcostal port where popular RPE approaches place the initial port.
      RESULTS: Eighteen procedures were performed in children with a mean age of 10.8
      years, including 12 nephrectomies, 3 dismembered pyeloplasties, 1 partial
      nephrectomy, 1 nephroureterectomy and 1 parapelvic cyst decortication. No gas
      leaks occurred, with 1 minor peritoneal entry early in the series not related to
      the access. Average surgical time for nephrectomy was 178 minutes (range 120 to
      240). No intraoperative complications occurred. CONCLUSIONS: We present a safe
      and effective technique of initial port placement that follows the principles of
      open lumbotomy exposure. This approach to RPE minimizes peritoneal entry and gas
      leaks, thus, maximizing surgical exposure.

PMID- 12796691
TI  - Bimanual digital rectal examination for the evaluation of the nonpalpable testis.
AB  - PURPOSE: In the evaluation and treatment of the nonpalpable testis open surgical
      exploration and laparoscopy are methods used to differentiate abdominal,
      infrainguinal (below the internal ring) and atrophic or absent testes. We sought
      to evaluate the use of bimanual digital rectal examination as an additional tool
      to localize the nonpalpable testis. MATERIALS AND METHODS: Forty-one consecutive
      patients with 45 nonpalpable testes were evaluated in a prospective fashion.
      Bimanual digital rectal examination was performed with the patients under general
      anesthesia just before diagnostic laparoscopy or open inguinal exploration.
      Palpability, location, length and contralateral testicular length were recorded.
      RESULTS: Twenty-five gonads or spermatic cords (56%) were palpable using the
      bimanual technique. All positive examinations were confirmed laparoscopically or
      by open exploration, and the majority of gonads were intra-abdominal (17 of 25,
      68%). Seventeen normal appearing gonads underwent orchiopexy and 8 were removed
      secondary to atrophy, dysgenesis or poor position. Twenty testes (44%) were not
      palpated using this method. Of these gonads 10 normal appearing testes were found
      at exploration and underwent orchiopexy. Of the 10 remaining gonads 6 atrophic
      testes were removed, and 4 hemosiderin laden remnants were thought to represent
      "vanished testes." Overall, 26 gonads or remnants were intra-abdominal, 10 were
      "peeping" or canalicular and 9 were infrainguinal. The overall specificity was
      100%, with a sensitivity of 60%. The positive predictive value was 100%.
      CONCLUSIONS: Bimanual digital rectal examination is a valuable tool in the
      evaluation of the nonpalpable testis, and identified the presence and position of
      the testis in the majority of our cases. Although sensitivity is low, when the
      testis is palpated by this method, diagnostic laparoscopy to localize the testis
      may be avoided.

PMID- 12796692
TI  - Minimally invasive treatment of vesicoureteral reflux with endoscopic injection
      of dextranomer/hyaluronic acid copolymer: the Children's Hospitals of Atlanta
      experience.
AB  - PURPOSE: Emerging data demonstrate that injection of dextranomer/hyaluronic acid
      (Dx/HA) copolymer (Deflux, Q-Med Scandinavia, Uppsala, Sweden) is a safe and
      effective treatment for most patients with vesicoureteral reflux (VUR). We sought
      to determine the efficacy and factors predictive of outcome in patients treated
      with Dx/HA. MATERIALS AND METHODS: A total of 180 children 7 months to 15 years
      old (mean age 4.6 years) underwent subureteral injection of Dx/HA for VUR between
      October 2001 and February 2003. Dx/HA was injected submucosally within or beneath
      the intramural ureter. The average volume of injected material was measured for
      each ureter. At 2 weeks and 3 months postoperatively bladder ultrasounds were
      performed to measure the volume of Dx/HA (mm3) in the trigone using the volume of
      an ellipsoid (V = 4/3pir(1)r(2)r(3)). Renal sonography was performed to determine
      whether hydronephrosis was present. At 3 months fluoroscopic voiding
      cystourethrograms were used to evaluate for the presence of VUR. RESULTS: A total
      of 292 ureters in 180 children were treated (112 bilateral cases). There were 141
      girls and 39 boys. Mean maximum grade per patient was 2.6 (out of 5). Average
      injected volume per ureter was 0.83 +/- 0.03 ml (830 +/- 30 mm3). At 2 weeks the
      average measured volume was 663 +/- 70 mm3 (18% decrease from original volume),
      which decreased an additional 1% by 3 months to 656 +/- 103 mm3. There were no
      cases of hydronephrosis at up to 12 months postoperatively.There were 134
      patients with at least 3 months of followup. After 1 treatment 72% (96) were
      cured (grade 0), while 55% of the failures (21 of 38) were improved. New
      contralateral VUR was seen in 6 patients (4.5%) who had neither a history of VUR
      nor an abnormal appearing ureteral orifice at cystoscopy. A lower success rate
      (60%) was seen in the first 20 patients compared with the last 20 patients (80%).
      The cure rate per grade was 90% for grade I, 82% for grade II, 73% for grade III
      and 65% for grade IV reflux. Local migration of material caudal to the ureteral
      orifice was seen in 61% of patients (11 of 18) at the time of reinjection of
      Dx/HA after initial treatment failure. There was no statistically significant
      difference in age, grade, volume injected, bilaterality or gender when successes
      were compared with failures. CONCLUSIONS: The majority of patients (72%)
      undergoing minimally invasive treatment of VUR with Dx/HA are cured after 1
      treatment. Contralateral treatment of nonrefluxing ureters should be considered
      in view of the increased incidence of new reflux (4.5%) and absence of morbidity
      with Dx/HA injection. There is a definite learning curve with injection therapy.
      The location of injected material and experience with the technique appear to
      correlate with the outcome of the procedure.

PMID- 12796693
TI  - Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly
      decrease their adhesion to renal cells.
AB  - PURPOSE: Adhesion of urinary crystals to renal tubular cells could be a critical
      event that triggers a cascade of responses ending in kidney stone formation. We
      clarified the role of urinary macromolecules during calcium oxalate monohydrate
      (COM) crystal adhesion to cells. MATERIALS AND METHODS: To assess COM crystal
      binding to cells in the presence of whole urine and fractions thereof we used
      monolayer cultures of distal nephron derived Madin-Darby canine kidney, type I
      cells as a model system. RESULTS: COM crystal adhesion to cells was decreased in
      the presence of whole urine compared with an ultrafiltrate prepared by passing
      urine through a 10 kDa cutoff membrane. Supplementing the ultrafiltrate with
      urinary concentrate containing proteins greater than 10 kDa returned crystal
      adhesion to low levels, similar to whole urine. Macromolecules in whole urine
      acted to decrease binding to cells by coating crystals and 4 proteins previously
      implicated in the pathogenesis of nephrolithiasis were detected on coated
      crystals (bikunin, osteopontin, prothrombin fragment 1 + 2 and Tamm-Horsfall
      glycoprotein). Crystals precipitated and grown in whole urine also bound less
      avidly to cells than crystals precipitated in artificial urine. CONCLUSIONS: This
      study confirms that macromolecules present in whole urine can coat crystals and,
      thereby, block their adhesion to renal tubular cells. Preventing crystal
      retention in the kidney could be an important mechanism whereby these
      macromolecules protect against kidney stones.

PMID- 12796694
TI  - Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for
      photodiagnosis of superficial bladder cancer--a multicenter study.
AB  - PURPOSE: We examined the sensitivity and specificity of Hexvix (PhotoCure ASA,
      Oslo, Norway) hexyl aminolevulinate (HAL) fluorescence cystoscopy in patients
      with superficial bladder cancer. MATERIALS AND METHODS: A total of 52 patients
      (38 men and 14 women) with a mean age of 72 years were investigated. HAL
      hydrochloride (100 mg dissolved in 50 ml phosphate buffer solution) (8 mM) was
      instilled into the bladder 1 hour prior to the endoscopic procedure. Cystoscopy
      was performed with the Storz D-light (Karl Storz, Tuttlingen, Germany) system,
      allowing inspection of the bladder wall under white and blue light (380 to 450
      nm). RESULTS: A total of 422 biopsies obtained in fluorescing (165) and
      nonfluorescing (257) areas, including 5 random biopsies per patient, were
      analyzed to provide the best reference for the calculation of sensitivity and
      specificity. There were a total of 143 histologically verified tumors in 45
      patients, including carcinoma in situ (CIS), Ta or T1 lesions. A total of 43
      patients were diagnosed by fluorescence cystoscopy compared with 33 diagnosed by
      white light for 96% and 73% per-patient sensitivity, respectively. HAL cystoscopy
      was found particularly useful for finding CIS tumors. Of 13 patients with CIS
      tumors all except 1 were diagnosed or confirmed by HAL cystoscopy. HAL cystoscopy
      was well tolerated with no definite drug related adverse events reported,
      including effects on standard blood parameters. CONCLUSIONS: HAL fluorescence
      cystoscopy is a new, sensitive, promising diagnostic procedure that showed
      improved detection of bladder tumors, in particular CIS. The procedure is well
      tolerated and can easily be implemented in current clinical practice.

PMID- 12796696
TI  - Regulation of androgen and vitamin d receptors by 1,25-dihydroxyvitamin D3 in
      human prostate epithelial and stromal cells.
AB  - PURPOSE: The mechanisms of the interaction between 1,25-dihydroxyvitamin D(3)
      (1,25 D) and androgens, and their respective receptors in their action on the
      prostate are not completely understood. We examined the interplay of 1,25 D and
      androgens on the epithelial and stromal cells of the prostate. MATERIALS AND
      METHODS: The human neonatal prostatic epithelial cell line 267B-1 (BRFF, Inc.,
      Ijamsville, Maryland) and primary cultures of human prostate stromal cells were
      treated with medium containing 5 or 10 microM 1,25 D or ethanol (control) in the
      presence or absence of 10 nM dihydrotestosterone (DHT) (Sigma Chemical Co., St.
      Louis, Missouri). Protein levels of androgen receptor (AR) and vitamin D receptor
      (VDR) were determined by immunoblot analysis of whole cell extracts.
      Electrophoresis mobility shift assays were used to determine AR and VDR DNA
      binding activities. RESULTS: The VDR protein level of 267B-1 cells was increased
      in the presence of 1,25 D (with the maximum effects seen at 24 hours) regardless
      of the presence or absence of DHT. In addition, exogenous DHT increased the AR
      and VDR DNA binding activities of 267B-1 and stromal cells in the presence of
      1,25 D. CONCLUSIONS: ARs in the normal prostate are regulated by androgens,
      whereas VDRs in the normal prostate can be regulated by 1,25 D as well as by
      other androgens such as testosterone. This finding further supports the concept
      that 1,25 D as a steroid hormone, in addition to other androgens such as DHT, may
      have a role in the growth and differentiation of normal prostate.

PMID- 12796695
TI  - Effect of intravesical treatment of transitional cell carcinoma with bacillus
      Calmette-Guerin and mitomycin C on urinary survivin levels and outcome.
AB  - PURPOSE: Urine survivin is a predictive/prognostic molecular marker that detects
      transitional cell carcinoma (TCC) with high specificity and sensitivity. The
      presence of urine survivin in patients with TCC who receive intravesical
      instillation of bacillus Calmette-Guerin or mitomycin C may predict recurrence.
      MATERIALS AND METHODS: Urine from 25 subjects receiving 27 intravesical
      treatments of bacillus Calmette-Guerin or mitomycin C for TCC were collected
      prior to, during and after treatment. Urinary survivin levels were compared with
      outcome, as assessed by cytology and cystoscopy with or without biopsy 1 month
      and up to 12 months after the completion of treatment. RESULTS: Pretreatment
      survivin levels were higher in subjects in whom TCC recurred following treatment
      compared with those who achieved remission. Survivin levels increased several
      fold during treatment with the highest survivin levels measured in subjects with
      recurrence. Median posttreatment values of survivin were zero in those who
      achieved remission and 1.0 ng/ml urine in subjects in whom TCC recurred.
      CONCLUSIONS: The presence of urinary survivin 1 month after the completion of
      treatment predicts TCC recurrence with 100% sensitivity and 78% specificity.
      Specificity to predict TCC recurrence increases to 92% after 1 year. No TCC
      recurred for 1 year in 12 of the 14 subjects with a posttreatment survivin level
      of 0.1 ng or less per ml urine. Three of the 4 subjects who were survivin
      positive but in remission 1 month after the completion of treatment had recurrent
      TCC within 1 year. Subjects who have urinary survivin after the completion of
      intravesical instillation have a high likelihood of TCC recurrence.

PMID- 12796697
TI  - Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent
      kinase inhibitor p27Kip1 in prostate cancer.
AB  - PURPOSE: Prostate carcinomas show a low level of the cell cycle inhibitor p27,
      which correlates with tumor aggressiveness. In tumors p27 is of the WT species
      and its deregulation is due to aberrant ubiquitin mediated degradation. The p27
      is degraded following phosphorylation and subsequent recognition by SCFSkp2
      ubiquitin ligase. We examined the relationship between p27 and its specific
      ligase Skp2 in normal and malignant prostate tissues. A possible correlation
      among the levels of these proteins, tumor grading and clinical state was also
      investigated. MATERIALS AND METHODS: Using immunohistochemistry
      immunofluorescence microscopy and Western blot analysis 51 samples from needle
      biopsies, transurethral resection and radical prostatectomy were analyzed for p27
      and Skp2 expression. Correlation with tumor grading (Gleason) was performed. In
      22 proven metastatic or organ confined cases correlation was also done with the
      Ki67 proliferative marker. RESULTS: Skp2 expression demonstrated a significant
      and direct correlation with malignancy (p <0.0001). Furthermore, a significant
      correlation was found between Skp2 level and tumor aggressiveness graded by
      Gleason score (p <0.0002) and prostate specific antigen. Patients with metastases
      had significantly higher Skp2 and Ki67 expression than those with organ confined
      disease (p <0.0001). In addition, Skp2 levels significantly correlated with Ki67
      (r = 0.73, p <0.0001). An inverse correlation was found between p27 and Skp2
      ligase. CONCLUSIONS: Skp2 expression in prostate biopsies may be used as an
      additional marker for tumor aggressiveness. The results also suggest a role for
      Skp2 in the pathogenesis of prostate malignancy.

PMID- 12796698
TI  - Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate
      pathway, impairing Ras membrane localization in prostate cancer cells.
AB  - PURPOSE: Metastasis to bone is an important cause of morbidity in advanced
      prostate cancer. Despite the typically sclerotic nature of prostatic bone
      metastases osteolysis has a significant role in the pathogenesis of this disease.
      The nitrogen containing bisphosphonates (N-BPs), such as pamidronate and
      zoledronic acid, have greatly enhanced potency for inhibiting bone resorption and
      inducing apoptosis in osteoclasts. We investigated the effects of N-BPs on
      prostate cancer cells. MATERIALS AND METHODS: Cell viability was determined with
      an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymeyhoxyphenyl)-2-(4-sulfophenyl)
      2H-tetrazolium) dye reduction assay. Cell cycle analysis, DNA fragmentation and
      caspase 3 activity were assessed using flow cytometry. Ras, Bcl-2 and Bax were
      quantified by Western blotting. RESULTS: Pamidronate and zoledronic acid
      decreased cell viability in the 3 human cell lines DU145, PC3 and LNCaP. These
      effects were associated with changes in cell cycle distribution, induction of DNA
      fragmentation and a decrease in the Bcl-2-to-Bax ratio, which are features of
      apoptotic cell death. Pre-incubation with caspase inhibitors attenuated the
      effects of zoledronic acid and caspase 3 activity was demonstrated in treated
      DU145 cells. Zoledronic acid induced loss of cell viability in DU145 cells was
      prevented by co-treatment with farnesol, suggesting that N-BPs cause inhibition
      of the mevalonate pathway and Ras prenylation. A decrease in active, membrane
      bound Ras in zoledronic acid treated DU145 cells was shown by Western blot
      analysis. CONCLUSIONS: N-BPs induce apoptosis in prostate cancer via a caspase
      dependent mechanism. They have effects on protein prenylation via inhibition of
      the mevalonate pathway and impair membrane localization of Ras in prostate cancer
      cells.

PMID- 12796699
TI  - Dimethyl sulfoxide: does it change the functional properties of the bladder wall?
AB  - PURPOSE: Dimethyl sulfoxide (DMSO) is used in a 50% solution to treat
      interstitial cystitis. Symptomatic relief occurs in about two-thirds of cases.
      The mechanism of action and effects of DMSO on bladder tissue function are poorly
      understood. Therefore, the effect of DMSO on bladder muscle compliance and
      contractility was evaluated. MATERIALS AND METHODS: Contractility and compliance
      were evaluated in rat bladder strips exposed to various concentrations of DMSO
      for 7 minutes, followed by 7 to 60-minute washout periods. The effect of DMSO at
      concentrations of 25%, 30%, 35%, 40% and 50% on electrical field stimulation
      induced contractions was assessed. Acetylcholine and high KCl (Sigma Chemical
      Co.) induced contractions were measured after exposure to 30% DMSO. Compliance
      was evaluated after exposure to 30% and 50% DMSO. RESULTS: Exposure to 40% DMSO
      completely abolished electrical field stimulation contractions, while 30% DMSO
      decreased the electrical field stimulation contraction to 40% +/- 6% of the
      initial force but there was almost complete recovery within 30 minutes.
      Contractile force was unaltered by 25% DMSO. Acetylcholine and KCl stimulation
      after exposure to 30% DMSO produced contractile forces of 78% +/- 6% and 39% +/-
      6% of pre-DMSO control contractions, respectively. Compliance decreased by 2.4
      and 4.6-fold following 30% and 50% DMSO exposure, respectively. CONCLUSIONS: DMSO
      completely and irreversibly abolishes contractions at a 40% concentration.
      Compliance is altered at even lower concentrations (30%). These findings bring
      into question the current practice of treating patients who have IC with 50%
      DMSO. Lower concentrations (25%) of DMSO may serve as a safe, effective analgesic
      and anti-inflammatory treatment for IC and other bladder pathologies.

PMID- 12796700
TI  - Ureteral function is modulated by a local renin-angiotensin system.
AB  - PURPOSE: Although many aspects of ureteral physiology are well characterized, the
      exact mechanism of ureteral smooth muscle modulation has not been fully
      established. In other smooth muscle contractility is modulated by angiotensin II
      (AngII). We determined the presence of a local ureteral renin-angiotensin system
      and characterized the functional role of AngII in ureteral smooth muscle.
      MATERIALS AND METHODS: Reverse transcriptase-polymerase chain reaction was
      performed to determine the expression of angiotensinogen, renin, angiotensin
      converting enzyme and angiotensin receptor subtype 1 mRNA. The presence of AngII
      in ureteral tissue was determined by immunohistochemistry. Human and pig ureteral
      smooth muscle strips were suspended in tissue baths to determine the effect of
      the AngII receptor antagonist losartan on the frequency and amplitude of
      spontaneous ureteral contractions. Electrical field stimulation was performed
      before and after exposure to losartan. RESULTS: Angiotensinogen, renin,
      angiotensin-converting enzyme and angiotensin receptor subtype 1 mRNA expression
      was detected in human ureter. Immunoreactivity for AngII was demonstrated in
      smooth muscle bundles and blood vessels of the ureter. Losartan decreased the
      amplitude and frequency of spontaneous ureteral contractions as well as the
      contractile response to electrical field stimulation in a dose dependent manner.
      CONCLUSIONS: Gene expression of AngII precursors and receptor, and localization
      of AngII in the ureter suggest the presence of a local renin-angiotensin system
      in the ureter. The effect of AngII receptor antagonist on contractile responses
      suggests that AngII modulates ureteral smooth muscle contractile function.
      Therefore, a local renin-angiotensin system may have an important role in
      ureteral function under physiological and pathological conditions.

PMID- 12796701
TI  - Pharmacological modulation of ureteral peristalsis in a chronically instrumented
      conscious pig model. I: Effect of cholinergic stimulation and inhibition.
AB  - PURPOSE: We evaluated in vivo the role of muscarinic receptors on ureteral
      peristaltic frequency and contraction force in a large animal model using
      pharmacological manipulation. MATERIALS AND METHODS: A total of 12 female pigs
      weighing a mean +/- SEM of 72 +/- 4 kg were chronically instrumented using an
      electronic pressure monitoring catheter in the right ureter. Furthermore,
      nephrostomy, arterial, venous and cystostomy catheters were placed. Ureteral
      peristalsis was repeatedly recorded before and after the administration of
      atropine and carbachol. RESULTS: Systemic and local effects of the 2 agents were
      observed. Compared with controls we recorded an increase in mean ureteral
      peristaltic frequency (2.0 +/- 0.3 versus 1.6 +/- 0.6 minutes-1, p <0.05) and
      mean contraction force (50.1 +/- 1.4 versus 45.3 +/- 1.7 cm H(2)O, p <0.05)
      during renal pelvis perfusion with 0.25 ml per minute saline. Administration of
      atropine or carbachol modulated neither the force of contraction nor the
      frequency of ureteral peristalsis in vivo (p >0.05). CONCLUSIONS: Smooth muscle
      motor activity at the mid and distal ureter is not modulated by muscarinic
      receptors. Peristaltic frequency is directly related to the pyelocaliceal load
      during a rate of diuresis not exceeding animal normal diuresis plus 0.25 ml per
      minute. Ureteral contraction force increases only in the mid ureter with
      increased diuresis.

PMID- 12796702
TI  - Norepinephrine inhibits the pelvic pressure increase in response to flow
      perfusion.
AB  - PURPOSE: We evaluated the effects of norepinephrine on transport pressures in the
      normal upper urinary tract of the pig during increasing perfusion rates.
      MATERIALS AND METHODS: Anesthetized Danish landrace Yorkshire pigs weighing 38 to
      40 kg were studied. Transparenchymally 2, 6Fr catheters were introduced into the
      left renal pelvis for pressure measurements and perfusion, respectively. An
      ultrasonic flow probe was inserted around the left renal artery to record blood
      flow. A 10Fr catheter was placed transurethrally for bladder drainage and the
      bladder was maintained empty during the entire study. In the 5 group 1 pigs the
      pelvic pressure increase was examined at increasing perfusion rates of the renal
      pelvis (2, 4, 6, 8, 10 and 15 ml per minute) in response to endoluminal
      administration of increasing concentrations of norepinephrine (0, 5, 50 and 100
      microg/ml) in saline. In the 5 group 2 pigs the pressure flow study was also done
      4 times per animal using isotonic saline. RESULTS: Endoluminal norepinephrine had
      a dose dependent effect on the pressure flow relationship. Perfusion with 5 and
      50 microg/ml norepinephrine caused a delayed increase and a decrease in pelvic
      pressure in response to increasing flow rates, whereas perfusion with 100
      microg/ml norepinephrine significantly inhibited and almost eliminated the
      pressure increase at all perfusion rates compared with saline perfusion.
      Importantly there were no changes in blood pressure, the heart rate or renal
      arterial blood flow. In group 2 perfusion with isotonic saline resulted in the
      same pressure response to increasing flow rates each time. CONCLUSIONS:
      Endoluminal administration of norepinephrine caused a dose dependent inhibition
      on the pressure phases of the pressure flow relationship of the upper urinary
      tract in pigs. No systemic changes were observed. These observations may provide
      a useful adjuvant treatment strategy for upper urinary tract stone treatment and
      endoscopy.

PMID- 12796703
TI  - Tramadol inhibits rat detrusor overactivity caused by dopamine receptor
      stimulation.
AB  - PURPOSE: In patients with Parkinson's disease an imbalance between stimulatory D2
      like receptors and inhibitory D1-like receptors may contribute to detrusor
      overactivity. Apomorphine, which stimulates D1-like and D2-like dopamine
      receptors, induces detrusor overactivity in rats. Tramadol is an analgesic drug
      that stimulates opioid receptors and inhibits reuptake of serotonin and
      noradrenaline. To evaluate a potentially inhibitory effect of tramadol the drug
      was given to rats with apomorphine induced detrusor overactivity. MATERIAL AND
      METHODS: Female Sprague-Dawley rats were used. During anesthesia catheters were
      introduced into the bladder dome, femoral vein and subcutaneously (SC). Three
      days later the rats were placed in a metabolism cage and voiding was stimulated
      by infusing saline into the bladder. Micturition parameters were recorded and
      compared after the administration of apomorphine and tramadol or vehicle.
      Desmopressin was given as pretreatment to suppress the diuresis produced by
      tramadol. RESULTS: While 30 microg kg-1 apomorphine SC was devoid of effect, 60
      and 100 microg kg-1 apomorphine SC induced a transient detrusor overactivity.
      Tramadol (1 mg kg-1) was without effect but 5 and 10 mg kg-1 tramadol
      intravenously attenuated the effects of apomorphine, while inducing prominent
      diuresis. Pretreatment with desmopressin, which did not alter cystometry or the
      effects of apomorphine, abolished diuresis. In these rats 5 and 10 mg kg-1
      tramadol intravenously abolished the overactivity caused by apomorphine SC.
      CONCLUSIONS: Tramadol effectively suppresses apomorphine induced detrusor
      overactivity in doses shown to have analgesic activity. Hence, tramadol may
      provide an approach to treat lower urinary tract disorders in which dopamine
      receptor activation is involved.

PMID- 12796705
TI  - Editorial: Spontaneous contractile activity in rat bladder.

PMID- 12796704
TI  - Partial outlet obstruction enhances modular autonomous activity in the isolated
      rat bladder.
AB  - PURPOSE: Autonomous bladder activity can take the form of localized micromotions
      (MMs), suggesting that the detrusor may be arranged into component modules, of
      which each is capable of contracting autonomously. We examined MMs in isolated
      whole rat bladder and the effects of partial bladder outlet obstruction as a
      model of detrusor overactivity (DO) to ascertain whether altered modular activity
      could be an etiological factor in DO. MATERIALS AND METHODS: A total of 12 adult
      female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4
      weeks. Bladders were microsurgically removed and mounted in whole organ tissue
      baths. Recordings of intravesical pressure and simultaneous registration of
      intramural contractions were performed under standardized conditions. RESULTS:
      Prior to filling MMs took the form of localized contractions near the
      vesicoureteral junction in sham operated animals and multifocal microcontractions
      in obstructed animals. Intravesical volume increases were associated with a
      change in localized MMs to propagated contraction waves. In sham operated animals
      stretch resulted in increased MM frequency but decreased amplitude. After
      obstruction stretch elicited highly coordinated MMs and enhanced intravesical
      pressure transmission. The time since surgery did not alter observations in the
      sham or obstructed group. CONCLUSIONS: Detrusor muscle in isolated bladders under
      conditions modeling urine storage may have a functional modular arrangement with
      the basolateral region most active prior to filling. Peripheral factors
      determining intravesical pressure include the number of modules active,
      coordination and intramural tension at other sites. After bladder outlet
      obstruction more modules are active at baseline and their coordination is
      enhanced by stretch, leading to increased pressure fluctuations. Such changes may
      contribute to the development of DO.

PMID- 12796706
TI  - Radiation increases fibrogenic cytokine expression by Peyronie's disease
      fibroblasts.
AB  - PURPOSE: Peyronie's disease is a crippling penile deformity that results from
      fibrosis in the tunica albuginea. To our knowledge its cause is unknown and
      empirical therapies are used extensively. A factor involved in the development of
      Peyronie's disease is fibrogenic cytokine over expression. Radiation therapy is
      an empirical therapy for this condition and, while some data suggest a role for
      it, no literature exists on the effects of radiation on tunical tissue or cells
      derived from this tissue. We evaluated the effect of radiation on fibrogenic
      cytokine production in cells cultured from Peyronie's disease plaque tissue.
      METHODS AND MATERIALS: Using a well established cell culture model cells derived
      from Peyronie's disease plaque tissue and neonatal foreskins were irradiated with
      5 Gy (treatment group) or left nonirradiated (control group). At 24 hours cells
      were harvested and the supernatant was analyzed using enzyme-linked immunosorbent
      assay to determine the levels of the 2 fibrogenic cytokines basic fibroblast
      growth factor and platelet-derived growth factor-AB. RESULTS: Four Peyronie's
      disease plaque derived cultures and 2 neonatal foreskin derived cultures were
      analyzed. All plaque derived fibroblasts demonstrated significant elevations in
      basic fibroblast growth factor and platelet-derived growth factor-AB compared
      with foreskin derived fibroblasts. CONCLUSIONS: These data suggest that radiation
      may in fact increase the production of fibrogenic cytokines, which may promote
      the fibrotic process involved in Peyronie's disease. Further study is aimed at
      defining the effect of irradiation on plaque tissue.

PMID- 12796707
TI  - The successful long-term treatment of age related erectile dysfunction with hSlo
      cDNA in rats in vivo.
AB  - PURPOSE: We have previously reported that 1 intracorporeal injection of 100
      microg hSlo/pcDNA reversed the effect of aging on erectile function in a rat
      model in vivo for at least 2 months. We report our further investigations of the
      amplitude, duration and physiological relevance of this novel gene transfer
      approach. MATERIALS AND METHODS: A total of 191 retired breeder Sprague-Dawley
      rats were given a single intracavernous injection of phosphate buffered saline,
      1,000 microg pcDNA, or 10, 100 or 1,000 microg pcDNA/hSlo. The animals were
      studied 1 to 6 months after injection. The intracorporeal pressure (ICP) response
      to cavernous nerve stimulation and immunostaining as well as hematoxylin and
      eosin staining were done to evaluate effector nerve integrity and tissue
      histology, respectively. RESULTS: Gene transfer prevented an age related decrease
      in resting ICP and a physiologically relevant, significant effect on normalizing
      erection in vivo, as determined by submaximal (0.5 mA) and maximal (4.0 mA)
      cavernous nerve stimulation. The effects were observed 1 month after transfection
      and sustained for 6 months at the 100 and 1,000 microg doses of pcDNA/hSlo (p
      <0.026). CONCLUSIONS: The physiological manifestations of gene transfer were
      detected as an amelioration of the age related decrease in resting ICP, and
      parallel increase in the magnitude of the cavernous nerve stimulated an ICP
      response to a level at which visible erections were again observed in this rat
      model of aging in vivo.

PMID- 12796708
TI  - Diabetes induced erectile dysfunction and apoptosis in penile crura are recovered
      by insulin treatment in rats.
AB  - PURPOSE: We hypothesized that apoptosis is a downstream event in erectile
      dysfunction, and pro-apoptotic (Bak and Bax) and anti-apoptotic (Bcl-2 and Bcl-x)
      factors are involved in the etiology of diabetes induced erectile dysfunction. To
      test this hypothesis the intracavernous pressure of diabetic and insulin treated
      rats was measured to assess erectile function. Molecular and immunohistochemical
      analyses for apoptosis were then performed in rat crura to assess their role in
      diabetes induced erectile dysfunction and insulin treatment. MATERIALS AND
      METHODS: A total of 70, 6-month-old male Sprague-Dawley rats were divided into 2
      groups, including a diabetic (50) and a healthy control (20) group. The diabetic
      group received intraperitoneal injection of streptozotocin (STZ) (Sigma-Aldrich
      Co., St. Louis, Missouri) to induce diabetes. Subcutaneous injection of insulin
      was administered daily to 9 diabetic rats 4 and 8 weeks after STZ injections for
      4 and 8 weeks, respectively. Functional studies were performed in 9 diabetic rats
      each 4, 8 and 12 weeks after STZ injections, in 6 age matched control rats and in
      insulin treated rats at the termination of therapy. After the completion of
      functional study the penile crura were collected from rats for molecular and
      immunohistochemical studies. RESULTS: Mean intracavernous pressure of diabetic
      rats was significantly lower than in control rats and the decrease in
      intracavernous pressure was significantly recovered by insulin treatment. Gene
      expressions of pro-apoptotic and anti-apoptotic factors were present in control,
      diabetic and insulin treated rat crura. However, anti-apoptotic protein
      expression was lacking in diabetic rat crura and pro-apoptotic protein expression
      was lost in insulin treated rat crura. The apoptotic index of diabetic rat crura
      was significantly higher than that of control rat crura and this index was
      significantly decreased in insulin treated rat crura. CONCLUSIONS: There was a
      significant correlation between the decrease and recovery in intracavernous
      pressure, and protein expression of apoptotic factors in diabetic and insulin
      treated rat crura. To our knowledge this is the first report demonstrating that
      the relief of diabetes associated erectile dysfunction by insulin treatment is
      due to alterations in the protein expression of apoptotic factors in rat crura.

PMID- 12796709
TI  - Microarray analysis and description of SMR1 gene in rat penis in a post-radical
      prostatectomy model of erectile dysfunction.
AB  - PURPOSE: We focused on the post-radical prostatectomy model to advance the
      understanding of neurogenic erectile dysfunction. We attempted to identify
      previously undescribed molecular changes via gene discovery methods using
      GeneChip (Affymetrix, Santa Clara, California) microarray technology. MATERIALS
      AND METHODS: Five male adult 120-day-old Sprague-Dawley rats underwent bilateral
      cavernous nerve neurectomy. Five age matched controls were prepared
      simultaneously. The penises were harvested on postoperative day 2 and snap frozen
      in liquid nitrogen. RNA was prepared and pooled into cut and uncut groups.
      Synthesis of cRNA was performed according to the GeneChip technical manual.
      Microarray analysis was performed on a U34A Rat Array (Affymetrix). This array
      has approximately 8,800 gene probe sets, approximately 6,600 known genes and
      approximately 2,200 estimated sequence transcripts. RESULTS: Dramatic results
      were found during GeneChip microarray expression analysis. A total of 126
      candidate genes were noted to be altered based on the magnitude of expression
      change using rigorous statistical criteria, including 47 that were down-regulated
      and 79 that were up-regulated. Among the many significant changes seen 1 dominant
      class of genes was the submandibular rat genes. Submandibular rat 1 (SMR1) was
      down-regulated 82.5 fold. Other genes in this family were down-regulated 226 and
      90 times. This result was confirmed by reverse transcriptase-polymerase chain
      reaction and Western blot analyses. These assays verified decreases in SMR1 at
      multiple time points after surgery. CONCLUSIONS: Impressive and previously
      unrecognized genetic changes are being intensely investigated as they are being
      unmasked by GeneChip technology. We have identified and begun the investigation
      of 1 interesting family of genes, namely submandibular gland proteins. The role
      of SMR as a clinically relevant change in penile and/or urethral function
      following cavernous nerve injury is speculative.

PMID- 12796710
TI  - Early orchiopexy restores fertility in the Hoxa 11 gene knockout mouse.
AB  - PURPOSE: We investigated whether infertility could be reversed in cryptorchid
      mice (with disrupted expression of the homeobox gene Hoxa 11) by orchiopexy and
      mating such animals with females of proven fertility. MATERIALS AND METHODS: Hoxa
      11 mutant and WT male mice were genotyped by polymerase chain reaction. Surgery
      (orchiopexy or sham operation) was performed at age 18 days and fertility was
      assessed at ages 6 to 8 weeks. Animals were sacrificed at ages 6 to 9 months and
      computer assisted semen analysis was performed on fluid obtained by epididymal
      puncture. RESULTS: Five of 28 mutant mice proved fertile following orchiopexy
      versus 0 of 22 after sham operation (p <0.05). Values in WT mice were 18 of 35
      and 25 of 33, respectively (p <0.01). Mean spermatozoa counts +/- SEM were 21.7
      +/- 5.9 x 106/ml in 8 mutant mice with orchiopexy, 2.78 +/- 1.59 x 106/ml in 8
      sham operated mutant mice (p <0.002), 15.6 +/- 4.9 x 106/ml in 7 WT mice with
      orchiopexy and 36.3 +/- 10.5 x 106/ml in 9 sham operated WT mice (p <0.02).
      CONCLUSIONS: Testicular position following orchiopexy is important to achieve
      fertility but the surgical procedure was associated with a degree of damage.
      Since mutant animals did not attain the fertility rates observed in WT animals
      following orchiopexy, other factors (possibly vaso-epididymal) may be necessary
      for normal spermatogenesis. Further studies of this model may allow the
      identification of such factors.

PMID- 12796711
TI  - Heme and iron metabolism: role in cerebral hemorrhage.
AB  - Heme and iron metabolism are of considerable interest and importance in normal
      brain function as well as in neurodegeneration and neuropathologically following
      traumatic injury and hemorrhagic stroke. After a cerebral hemorrhage, large
      numbers of hemoglobin-containing red blood cells are released into the brain's
      parenchyma and/or subarachnoid space. After hemolysis and the subsequent release
      of heme from hemoglobin, several pathways are employed to transport and
      metabolize this heme and its iron moiety to protect the brain from potential
      oxidative stress. Required for these processes are various extracellular and
      intracellular transporters and storage proteins, the heme oxygenase isozymes and
      metabolic proteins with differing localizations in the various brain-cell types.
      In the past several years, additional new genes and proteins have been discovered
      that are involved in the transport and metabolism of heme and iron in brain and
      other tissues. These discoveries may provide new insights into neurodegenerative
      diseases like Alzheimer's, Parkinson's, and Friedrich's ataxia that are
      associated with accumulation of iron in specific brain regions or in specific
      organelles. The present review will examine the uptake and metabolism of heme and
      iron in the brain and will relate these processes to blood removal and to the
      potential mechanisms underlying brain injury following cerebral hemorrhage.

PMID- 12796712
TI  - Contribution of the heme oxygenase pathway to the maintenance of the hypothalamic
      blood flow during diminished nitric oxide synthesis.
AB  - The cerebrovascular effects of the heme oxygenase-carbon monoxide pathway were
      studied in the rat hypothalamus. Intraperitoneal administration of the heme
      oxygenase inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, 45 micro
      mol/kg) had no significant effect on the resting cerebral blood flow, but
      increased hypothalamic nitric oxide synthase activity by 67% without changing the
      CSF cyclic GMP concentration. After pharmacologic inhibition of nitric oxide
      synthase, the diminished cerebral blood flow was further reduced by 22% after
      administration of ZnDPBG, and the effect showed direct correlation with the
      baseline perfusion level. Therefore, endogenous carbon monoxide may significantly
      contribute to the cerebral vasoregulation under resting conditions and in
      pathophysiologic states associated with diminished nitric oxide synthesis.

PMID- 12796713
TI  - Lactate: a preferred fuel for human brain metabolism in vivo.
AB  - Recent in vitro studies suggest that lactate, rather than glucose, may be the
      preferred fuel for neuronal metabolism. The authors examined the effect of
      lactate on global brain glucose uptake in euglycemic human subjects using 18
      fluoro-deoxyglucose (FDG) positron emission tomography (PET). Eight healthy men,
      aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in
      random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50
      micro mol. kg-1. min-1 for 20 minutes and then reduced to 30 micro mol. kg-1. min
      1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma
      glucose levels were not different between the two groups (5.3 +/- 0.23 and 5.3 +/
      0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate
      infusion (4.08 +/- 0.35 vs. 0.63 +/- 0.22 mmol/L, P < 0.0005. The whole-brain
      rate of glucose uptake was significantly reduced by approximately 17% during
      lactate infusion (0.195 +/- 0.022 vs. 0.234 +/- 0.020 micro mol. g-1. min-1, P =
      0.001). The authors conclude that, in vivo in humans, circulating lactate is used
      by the brain at euglycemia, with sparing of glucose.

PMID- 12796714
TI  - Changes in human cerebral blood flow and cerebral blood volume during hypercapnia
      and hypocapnia measured by positron emission tomography.
AB  - Hypercapnia induces cerebral vasodilation and increases cerebral blood flow
      (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The
      relation between changes in CBF and cerebral blood volume (CBV) during
      hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV
      were measured at rest and during hypercapnia and hypocapnia in nine healthy
      subjects by positron emission tomography. The vascular responses to hypercapnia
      in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg,
      respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/-
      1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09
      CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia,
      indicating an increase in vascular blood velocity. The degree of decrease in CBF
      during hypocapnia was greater than that in CBV, indicating a decrease in vascular
      blood velocity. The relation between changes in CBF and CBV during hypercapnia
      was similar to that during neural activation; however, the relation during
      hypocapnia was different from that during neural deactivation observed in crossed
      cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be
      governed by a similar microcirculatory mechanism between neural activation and
      hypercapnia, but diminution of CBF and CBV might be governed by a different
      mechanism between neural deactivation and hypocapnia.

PMID- 12796715
TI  - Development of injectable O-15 oxygen and estimation of rat OEF.
AB  - Cerebral metabolic rate for oxygen (CMRO(2)) and cerebral oxygen extraction
      fraction (OEF) are some of the most fundamental parameters to characterize the
      pathophysiologic status of cerebral tissue. Although O-15-labeled gases
      inhalation method is performed in clinical studies, application of the inhalation
      method on small animals requires too many intensive procedures. On this basis,
      the development of a new method to measure CMRO(2) and OEF in small animals is of
      interest. This study was aimed at developing a method to assess CMRO(2) and OEF
      using intravenously injectable oxygen (injectable 15O-O(2)) for small animals
      such as rats. Injectable 15O-O(2), 72 MBq/mL of radioactivity, was obtained after
      15O-O(2) gas circulation into the artificial lung. OEF after injection of
      injectable 15O-O(2) was calculated using the same equation as that applied to the
      bolus inhalation of 15O-O(2) gas method. Values of 44 +/- 4.5 mL. min-1. 100 g-1
      of CBF and 0.54 +/- 0.11 of OEF were obtained (n = 13). This OEF value was well
      accordance with OEF evaluated by arterial-venous difference of oxygen
      concentration (0.57 +/- 0.13). This method is useful to study the CMRO(2) and OEF
      in small animals using an animal positron emission tomography system. It may
      accelerate the basic research of several cerebral perfusion diseases.

PMID- 12796716
TI  - Temporal relation between the ADC and DC potential responses to transient focal
      ischemia in the rat: a Markov chain Monte Carlo simulation analysis.
AB  - Markov chain Monte Carlo simulation was used in a reanalysis of the longitudinal
      data obtained by Harris et al. (J Cereb Blood Flow Metab 20:28-36) in a study of
      the direct current (DC) potential and apparent diffusion coefficient (ADC)
      responses to focal ischemia. The main purpose was to provide a formal analysis of
      the temporal relationship between the ADC and DC responses, to explore the
      possible involvement of a common latent (driving) process. A Bayesian nonlinear
      hierarchical random coefficients model was adopted. DC and ADC transition
      parameter posterior probability distributions were generated using three parallel
      Markov chains created using the Metropolis algorithm. Particular attention was
      paid to the within-subject differences between the DC and ADC time course
      characteristics. The results show that the DC response is biphasic, whereas the
      ADC exhibits monophasic behavior, and that the two DC components are each
      distinguishable from the ADC response in their time dependencies. The DC and ADC
      changes are not, therefore, driven by a common latent process. This work
      demonstrates a general analytical approach to the multivariate, longitudinal data
      processing problem that commonly arises in stroke and other biomedical research.

PMID- 12796717
TI  - Comparative study of the FAIR technique of perfusion quantification with the
      hydrogen clearance method.
AB  - Arterial spin labeling magnetic resonance methods, including flow-sensitive
      alternating inversion recovery (FAIR), are becoming increasingly common for the
      noninvasive quantification of cerebral blood flow (CBF). This report compares the
      FAIR method with hydrogen clearance. The latter is an established, invasive
      technique for CBF measurement in animals. Paired readings of CBF were obtained in
      gerbils to maximize the degree of spatial and temporal correspondence between
      methods. Flow-sensitive alternating inversion recovery (50 averages, 6.7-minute
      measurement time) and hydrogen clearance measurements were made concurrently.
      Cerebral blood flow values measured by both techniques displayed an initial
      decrease because of the injurious effects of electrode insertion and subsequent
      recovery. Mixed model regression analysis, structural equations modeling, and a
      simple concordance correlation coefficient analysis were performed. No evidence
      of a marked systematic bias in the FAIR measurements was found; mixed model
      regression analysis yielded relative bias estimates of 0.4 (confidence interval:
      3.0, 3.9) mL. 100 g-1. min-1 and -3.7 (-12.1, 4.7) mL. 100 g-1. min-1 at 20 and
      100 mL. 100 g-1. min-1, respectively. The principal limitation of the FAIR
      technique was the magnitude of the random measurement error (imprecision), which
      had a standard deviation on the order of 10 mL. 100 g-1. min-1.

PMID- 12796718
TI  - N-acetylaspartate to total creatine ratio in the hippocampal CA1 sector after
      transient cerebral ischemia in gerbils: influence of neuronal elements, reactive
      gliosis, and tissue atrophy.
AB  - The authors compared temporal profiles of N-acetylaspartate (NAA) and the
      NAA/total creatine ratio with neuronal and astrocytic densities and with tissue
      atrophy in the hippocampal CA1 sector of gerbils after 5-minute bilateral
      forebrain ischemia and subsequent reperfusion for up to 6 months. The CA1 sector
      was dissected from 20- micro m lyophilized sections (n = 5) for NAA,
      phosphocreatine, and creatine assays using high-performance liquid
      chromatography. Adjacent 10- micro m sections were used for immunohistochemical
      analysis to follow neuronal and astrocytic responses. The NAA concentration was
      significantly (P<0.01) decreased after 7 days but leveled off thereafter. The
      NAA/total creatine (phosphocreatine + creatine) ratio was significantly decreased
      after 7 days and further decreased (P<0.05) after 6 months. Extensive neuronal
      damage developed beyond 7 days, while reactive astrogliosis progressed throughout
      the observation period. There was a good linear correlation (P<0.01) between
      astroglial density and the NAA/total creatine ratio beyond 7 days. The thickness
      of the CA1 sector was significantly reduced after 1 month and further reduced
      after 6 months. Although both NAA level and the NAA/total creatine ratio seemed
      to be indicators of neuronal damage, the latter could be influenced by reactive
      astrogliosis with progression of tissue atrophy.

PMID- 12796720
TI  - Overexpression of rat heat shock protein 70 is associated with reduction of early
      mitochondrial cytochrome C release and subsequent DNA fragmentation after
      permanent focal ischemia.
AB  - Although protective effects of heat shock protein 70 (HSP70) overproduction after
      ischemic injury have been shown both in vitro and in vivo in neurons, the
      mechanisms are not fully understood. The hypothesis of this study is that
      transgenic mice overexpressing HSP70 (HSP70 Tg) show reduced mitochondrial
      cytochrome c release into cytosol and diminished apoptotic cell death after
      permanent focal ischemia in comparison to wild-type (Wt) mice. Permanent middle
      cerebral artery occlusion (pMCAO) was produced by intraluminal suture cannulation
      in HSP70 Tg and Wt mice. DNA fragmentation was evaluated with DNA gel
      electrophoresis and terminal deoxynucleotidyl transferase-mediated biotinylated
      UTP nick end labeling (TUNEL) 24 h after pMCAO. Mitochondrial cytochrome c
      release into cytosol was assessed with Western blotting and immunohistochemistry
      4 h after pMCAO. Cytochrome c levels in the cytosolic fraction were significantly
      reduced and immunoreactivity of cytochrome c in both cortex and striatum was
      significantly less in HSP70 Tg mice compared with Wt mice after 4-h pMCAO. DNA
      laddering, which was clearly observed in Wt mice, was markedly attenuated in
      HSP70 Tg mice 24 h after pMCAO. The number of TUNEL-positive cells was
      significantly reduced in HSP70 Tg mice compared with Wt mice. Results are
      consistent with an association between overexpression of HSP70 and reduction of
      cytochrome c release with subsequent DNA fragmentation. This may contribute to
      the HSP70-mediated neuroprotective effect observed after cerebral ischemia.

PMID- 12796719
TI  - Participation of bone marrow-derived cells in long-term repair processes after
      experimental stroke.
AB  - Bone marrow-derived cells participate in remodeling processes of many ischemia
      associated diseases, which has raised hopes for the use of bone marrow as a
      source for cell-based therapeutic approaches. To study the participation of bone
      marrow-derived cells in a stroke model, bone marrow from C57BL/6
      TgN(ACTbEGFP)1Osb mice that express green fluorescent protein (GFP) in all cells
      was transplanted into C57BL/6J mice. The recipient mice underwent permanent
      occlusion of the middle cerebral artery, and bone marrow-derived cells were
      tracked by fluorescence. The authors investigated the involvement of bone marrow
      derived cells in repair processes 6 weeks and 6 months after infarction. Six
      weeks after occlusion of the artery, more than 90% of the GFP-positive cells in
      the infarct border zone were microglial cells. Very few GFP-positive cells
      expressed endothelial markers in the infarct/infarct border zone, and no bone
      marrow-derived cells transdifferentiated into astrocytes, neurons, or
      oligodendroglial cells at all time points investigated. The results indicate the
      need for additional experimental studies to determine whether therapeutic
      application of nonselected bone marrow will replenish brain cells beyond an
      increase in microglial engraftment.

PMID- 12796721
TI  - The Ras inhibitor S-trans, trans-farnesylthiosalicylic acid exerts long-lasting
      neuroprotection in a mouse closed head injury model.
AB  - Traumatic brain injury activates N-methyl-d-aspartate receptors (NMDAR) inducing
      activation of the Ras protein (a key regulator of cell growth, survival, and
      death) and its effectors. Thus, trauma-induced increase in active Ras-GTP might
      contribute to traumatic brain injury pathology. Based on this hypothesis, a new
      concept of neuroprotection is proposed, examined here by investigating the effect
      of the Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) in a mouse
      model of closed head injury (CHI). Mice subjected to CHI were treated
      systemically 1 h later with FTS (5 mg/kg) or vehicle. After 1 h, Ras-GTP in the
      contused hemisphere showed a significant (3.8-fold) increase, which was strongly
      inhibited by FTS (82% inhibition) or by the NMDA-receptor antagonist MK-801
      (53%). Both drugs also decreased active (phosphorylated) extracellular signal
      regulated kinase. FTS prevented the CHI-induced reduction in NMDAR binding in
      cortical, striatal, and hippocampal regions, measured by [3H]-MK-801
      autoradiography, and decreased lesion size by 50%. It also reduced CHI-induced
      neurologic deficits, indicated by the highly significant (P < 0.0001) 60%
      increase in extent of recovery. Thus, FTS provided long-term neuroprotection
      after CHI, rescuing NMDAR binding in the contused hemisphere and profoundly
      reducing neurologic deficits. These findings suggest that nontoxic Ras inhibitors
      such as FTS may qualify as neuroprotective drugs.

PMID- 12796722
TI  - Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3
      activation and increases glial proliferation after ischemia in near-term fetal
      sheep.
AB  - Insulin-like growth factor (IGF-1) markedly increases myelination and glial
      numbers in white matter after ischemia in near-term fetal sheep; however, it is
      unclear whether this is due to reduced cell loss or increased secondary
      proliferation. Brain injury was induced in near-term fetal sheep by 30 minutes of
      bilateral carotid artery occlusion. Ninety minutes after the occlusion, fetuses
      were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or
      30 micro g), or 3 micro g followed by 3 micro g over 24 hours (3 + 3 micro g).
      White matter was assessed 4 days after reperfusion. Three micrograms, but not 30
      micro g of IGF-1 prevented loss of oligodendrocytes and myelin basic protein
      density (P < 0.001) compared to the vehicle-treated ischemia controls. No
      additional effect was observed in the 3 + 3 micro g group. IGF-1 treatment was
      associated with reduced caspase-3 activation and increased glial proliferation in
      a similar dose-dependent manner. Caspase-3 was only expressed in oligodendrocytes
      that showed apoptotic morphology. Proliferating cell nuclear antigen co-localized
      with both oligodendrocytes and astrocytes and microglia. Thus, increased
      oligodendrocyte numbers after IGF-1 treatment is partly due to suppression of
      apoptosis, and partly to increased proliferation. In contrast, the increase in
      reactive glia was related only to proliferation. Speculatively, reactive glia may
      partly mediate IGF-1 white matter protection.

PMID- 12796724
TI  - Energy metabolism in astrocytes and neurons treated with manganese: relation
      among cell-specific energy failure, glucose metabolism, and intercellular
      trafficking using multinuclear NMR-spectroscopic analysis.
AB  - A central question in manganese neurotoxicity concerns mitochondrial dysfunction
      leading to cerebral energy failure. To obtain insight into the underlying
      mechanism(s), the authors investigated cell-specific pathways of [1-13C]glucose
      metabolism by high-resolution multinuclear NMR-spectroscopy. Five-day treatment
      of neurons with 100-micro mol/L MnCl(2) led to 50% and 70% decreases of ATP/ADP
      and phosphocreatine-creatine ratios, respectively. An impaired flux of [1
      13C]glucose through pyruvate dehydrogenase, which was associated with Krebs cycle
      inhibition and hence depletion of [4-13C]glutamate, [2-13C]GABA, and
      [13C]glutathione, hindered the ability of neurons to compensate for mitochondrial
      dysfunction by oxidative glucose metabolism and further aggravated neuronal
      energy failure. Stimulated glycolysis and oxidative glucose metabolism protected
      astrocytes against energy failure and oxidative stress, leading to twofold
      increased de novo synthesis of [3-13C]lactate and fourfold elevated [4
      13C]glutamate and [13C]glutathione levels. Manganese, however, inhibited the
      synthesis and release of glutamine. Comparative NMR data obtained from cocultures
      showed disturbed astrocytic function and a failure of astrocytes to provide
      neurons with substrates for energy and neurotransmitter metabolism, leading to
      deterioration of neuronal antioxidant capacity (decreased glutathione levels) and
      energy metabolism. The results suggest that, concomitant to impaired neuronal
      glucose oxidation, changes in astrocytic metabolism may cause a loss of
      intercellular homeostatic equilibrium, contributing to neuronal dysfunction in
      manganese neurotoxicity.

PMID- 12796723
TI  - Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates
      ischemic brain injury and is associated with recruitment of inflammatory cells.
AB  - Brain cells produce cytokines and chemokines during the inflammatory process
      after stroke both in animal models and in patients. Monocyte chemoattractant
      protein 1 (MCP-1), one of the proinflammatory chemokines, can attract monocytes
      to the tissue where MCP-1 is overexpressed. However, the role of MCP-1 elevation
      in stroke has not been explored in detail. The authors hypothesized that elevated
      MCP-1 levels would lead to increased influx of monocytes and increased brain
      infarction size in stroke induced by middle cerebral artery occlusion with
      partial reperfusion. There were no differences in blood pressure, blood flow, or
      vascular architecture between wild-type mice and transgenic MBP-JE mice. Twenty
      four to 48 hours after middle cerebral artery occlusion, brain infarction volumes
      after ischemia were significantly larger in MBP-JE mice than in wild-type
      controls and were accompanied by increased local transmigration and perivascular
      accumulation of macrophages and neutrophils. These results indicate that MCP-1
      can contribute to inflammatory injury in stroke.

PMID- 12796725
TI  - Immunobiology of epithelial chemokines in the intestinal mucosa.

PMID- 12796726
TI  - Patient entry into randomized controlled trials of colorectal cancer treatment:
      factors influencing participation.
AB  - BACKGROUND: The objective of this study was to investigate willingness to
      participate in hypothetical surgical randomized controlled trials (RCTs) among
      patients and clinicians, who answered as if they themselves were patients.
      METHODS: We interviewed consecutive patients with colorectal cancer admitted for
      surgery at a tertiary center in Sydney, Australia. We mailed a questionnaire to
      all colorectal surgeons and medical oncologists in Australia. RESULTS: Overall,
      42% (95% CI, 32% to 52%) of patients, 44% (95% CI, 29% to 60%) of surgeons, and
      63% (95% CI, 53% to 72%) of oncologists were willing to enter a randomized
      clinical trial. Oncologists were significantly more likely to participate than
      either surgeons (P <.001) or patients (P =.001). No significant associations were
      seen between willingness to participate and patient characteristics. "Risk of
      cancer recurrence" was rated by the most patients and doctors as an important
      reason for refusal of trial entry, although patients additionally identified
      dislike of randomization and quality of life concerns as important barriers.
      CONCLUSION: More than 40% of patients were willing to enter into a hypothetical
      RCT involving surgery. Aversion to randomization and perceptions of differential
      impact of treatment on cancer recurrence and quality of life are likely to be
      major barriers to patient accrual in trials of colorectal cancer treatment.

PMID- 12796727
TI  - Analysis of errors reported by surgeons at three teaching hospitals.
AB  - BACKGROUND: Little is known of the factors that underlie surgical errors.
      Incident reporting has been proposed as a method of obtaining information about
      medical errors to help identify such factors. METHODS: Between November 1, 2000,
      and March 15, 2001, we conducted confidential interviews with randomly selected
      surgeons from three Massachusetts teaching hospitals to elicit detailed reports
      on surgical adverse events resulting from errors in management ("incidents").
      Data on the characteristics of the incidents and the factors that surgeons
      reported to have contributed to the errors were recorded and analyzed. RESULTS:
      Among 45 surgeons approached for interviews, 38 (84%) agreed to participate and
      provided reports on 146 incidents. Thirty-three percent of incidents resulted in
      permanent disability and 13% in patient death. Seventy-seven percent involved
      injuries related to an operation or other invasive intervention (visceral
      injuries, bleeding, and wound infection/dehiscence were the most common
      subtypes), 13% involved unnecessary or inappropriate procedures, and 10% involved
      unnecessary advancement of disease. Two thirds of the incidents involved errors
      during the intraoperative phase of surgical care, 27% during preoperative
      management, and 22% during postoperative management. Two or more clinicians were
      cited as substantially contributing to errors in 70% of the incidents. The most
      commonly cited systems factors contributing to errors were inexperience/lack of
      competence in a surgical task (53% of incidents), communication breakdowns among
      personnel (43%), and fatigue or excessive workload (33%). Surgeons reported
      significantly more systems failures in incidents involving emergency surgical
      care than those involving nonemergency care (P <.001). CONCLUSIONS: Subjective
      incident reports gathered through interviews allow identification of
      characteristics of surgical errors and their leading contributing factors, which
      may help target research and interventions to reduce such errors.

PMID- 12796728
TI  - Invited commentary: is it a mistake to focus on errors?

PMID- 12796729
TI  - Invited commentary: analyzing adverse medical events--it's the system!

PMID- 12796730
TI  - Prognostic factors for poor survival after repeat hepatectomy in patients with
      colorectal liver metastases.
AB  - BACKGROUND: The recurrence rate for colorectal liver metastases after repeat
      hepatic resection is high, and selection criteria for repeat hepatectomy are
      still controversial. METHODS: Clinical data of patients undergoing repeat
      hepatectomy for metastatic colon cancer were reviewed retrospectively and
      compared with those of initial hepatectomy and other treatments to determine
      criteria for repeat hepatectomy and to confirm its efficacy. RESULTS: For 22
      patients who underwent repeat hepatectomy, no mortality and an 18% morbidity rate
      were observed. The 3-year survival rate after repeat hepatectomy was 49%. The
      only poor prognostic factor after repeat hepatectomy was a serum carcinoembryonic
      antigen level greater than 50 ng/mL before initial hepatectomy. The prognosis for
      patients who underwent repeat hepatectomy and had shown high carcinoembryonic
      antigen levels before initial hepatectomy was approximately equal to that for the
      patients who received systemic chemotherapy or hepatic arterial infusion for
      unresectable tumors in the remnant liver. CONCLUSION: Repeat hepatectomy for
      colorectal liver metastases can be performed safely and appears to be as
      effective as initial hepatectomy. However, for patients with a carcinoembryonic
      antigen level greater than 50 ng/mL before the initial hepatectomy, repeat
      hepatic resection alone may not be as effective, and a new strategy is needed.

PMID- 12796731
TI  - Hydro-Jet-assisted laparoscopic cholecystectomy: a prospective randomized
      clinical study.
AB  - BACKGROUND: A new dissection technique with high-pressure water stream (Hydro
      Jet) has recently been applied for selective dissection during various surgical
      procedures. The aim of this study was to compare Hydro-Jet with the conventional
      technique for laparoscopic cholecystectomy. METHODS: Eighty patients were
      randomized to undergo laparoscopic cholecystectomy with standard (n = 40) or
      Hydro-Jet-assisted (n = 40) dissection techniques. The rates of intraoperative
      complications, including blood loss and injury to the adjacent organs, were
      compared between the groups. The versatility of this technique and the features
      of surgical dissection were also evaluated and compared. RESULTS: Laparoscopic
      cholecystectomy was successfully completed in all subjects. The mean operative
      times were 78 minutes (range, 52-120 minutes) and 81 minutes (range, 45-135
      minutes) for Hydro-Jet versus conventional dissection, respectively (P = not
      significant). Complications included gallbladder perforation in 15% and 30% (P
      <.1) and liver laceration in 0% and 10% (P <.04) with Hydro-Jet and conventional
      techniques, respectively. Increased hemorrhage from the gallbladder bed that
      necessitated fulguration occurred in 12 patients with the conventional technique
      as compared with none in the Hydro-Jet group (P <.001). Hydro-Jet resulted in a
      selective dissection of connective tissue preserving blood vessels and the cystic
      duct. The continuous water flow allowed a clear view for the operator, and the
      dissection was performed in a relatively bloodless field. The ease of blunt
      dissection with the bent-tip dissector represents another advantage. CONCLUSION:
      This study shows that Hydro-Jet dissection represents an excellent alternative to
      the conventional technique for laparoscopic cholecystectomy. The improved
      anatomic dissection combined with an almost bloodless operating field as the
      result of continuous water flow decreased the rate of dissection-related
      complications.

PMID- 12796732
TI  - Renal anomalies in aortic surgery: contemporary results.
AB  - OBJECTIVE: The purpose of this study was to evaluate technical problems and
      results of surgical treatment of aortic disease associated with major renal
      anomalies. STUDY DESIGN: Renal anomalies observed during aortic procedures
      performed over a 19-year period were reviewed. Type of renal anomaly, diagnostic
      procedures, preoperative renal function, technique of vascular reconstruction,
      and management of the anomalous kidney were considered and correlated with peri
      operative and long-term results. RESULTS: Eighteen patients (1.1%) with major
      renal abnormalities were found in our experience with more than 1650 aortic
      procedures. Of these, 10 involved horseshoe kidneys and 8 ectopic kidneys (3
      pelvic, 3 lumbar, and 2 crossed ectopias). All elective cases were evaluated with
      computed tomography, urography, and angiography. Aortic reconstruction was
      performed in 17 patients for aortic aneurysm (1 urgent repair for rupture) and in
      1 patient for obstructive disease. Surgical access was anterior transperitoneal
      in 16 patients and retroperitoneal/thoracoabdominal in 2. In 8 patients,
      reimplantation of 1 or both renal arteries was necessary. Division of the renal
      isthmus was necessary in 3 patients with horseshoe kidney. The perioperative
      mortality rate was 0%. Renal function was normal at discharge in all patients. At
      long-term follow-up (median, 5 years; range, 1 to 19 years) neither renal nor
      aortic complications were detected. In 15 of 17 patients, the aneurysm was
      confined to the abdominal aorta. CONCLUSION: Although infrequent, renal anomalies
      encountered during aortic surgery can be effectively treated with accurate
      diagnosis and preoperative planning.

PMID- 12796733
TI  - Erythromycin induces pyloric relaxation accompanied by a contraction of the
      gastric body after pylorus-preserving gastrectomy.
AB  - BACKGROUND: Pylorus-preserving gastrectomy (PPG) is a function-preserving
      surgery; however, long-term retention of food in the residual stomach is a
      frequent complication during the early postoperative period. We reported that
      gastric stasis after PPG was attributable to the delayed recovery of gastric
      phase III, in which pyloric relaxation accompanied a contraction of the gastric
      body. The objective of the present study is to determine whether erythromycin can
      induce phase III with pyloric relaxation after PPG. METHODS: We studied
      gastrointestinal motility in dogs after PPG by using strain gauge force
      transducer. After randomized administration of either erythromycin or saline,
      interdigestive gastropyloroduodenal motility was recorded. RESULTS: Erythromycin
      induced phase III with pyloric relaxation in the early postoperative period.
      Pyloric relaxation accompanied a contraction of the gastric body. Compared with
      the saline group (body: 87.2 +/- 16.7 mmHg x min, antrum: 69.7 +/- 13.7 mmHg x
      min, pylorus: 91.7 +/- 22.1 mmHg x min), the erythromycin group showed
      significantly increased gastropyloric motility indexes (body: 506.2 +/- 33.5 mmHg
      x min, antrum: 430.9 +/- 53.7 mmHg x min, pylorus: 589.5 +/- 59.5 mmHg x min).
      CONCLUSIONS: Erythromycin can induce phase III, in which pyloric relaxation
      accompanied a contraction of the gastric body in the early postoperative period
      after PPG. Erythromycin might be used as a prokinetic agent for the treatment of
      early gastric stasis after PPG.

PMID- 12796734
TI  - Magnetic resonance imaging predicts sphincter invasion of low rectal cancer and
      influences selection of operation.
AB  - BACKGROUND: With the development of numerous sphincter-saving surgical techniques
      in the last 2 decades, the indication for abdominoperineal resection in radical
      elective operations has been markedly reduced. The preoperative assessment of the
      extent of local tumor growth is essential for the planning of the optimal
      surgical procedure. Magnetic resonance imaging (MRI) proved to be a reliable
      method for local staging of low rectal carcinoma. The objective of this study was
      to determine the frequency of sphincter invasion in an unselected population with
      low rectal cancer. METHODS: From 1997 to 1999, 40 patients with histologically
      verified adenocarcinoma of the lower rectum (+/-5 cm above the linea dentata)
      without evidence of metastases underwent a MRI with a body coil (no anal
      endocoil). The MRI results were compared with the operative situs and with
      pathohistologic findings. RESULTS: An infiltration of the sphincter ani internus
      was observed in 11 cases (28%), and a combined infiltration of the sphincter ani
      internus and externus was found in 2 patients (5%). The median distance of the
      lower tumor edge to the upper border of the anal canal was 2.0 cm (range, 0-4.5
      cm). No infiltration of the external sphincter was observed in patients with
      cancers above the anal canal. Nine patients (22%) were treated with
      intersphincteric resection and coloanal anastomosis, 12 (30%) with ultralow
      resection, and 11 (28%) with low anterior resection of the rectum in conjunction
      with coloanal anastomosis or a stapled anastomosis. Eight (17%) of the patients
      were treated with abdominoperineal resection. CONCLUSION: An infiltration of the
      internal sphincter occurs only in 28% of low rectal cancers; an infiltration of
      the external anal sphincter is extremely rare and occurred only in patients with
      cancers located in the anal canal. Pelvic MRI offers a precise preoperative
      visualization of sphincter infiltration in patients with low rectal cancers and
      is therefore a valuable tool for planning of rectal surgery.

PMID- 12796735
TI  - Correlation between serum melatonin circadian rhythm and intensive care unit
      psychosis after thoracic esophagectomy.
AB  - BACKGROUND: Intensive care unit (ICU) psychosis is still a relatively frequent
      complication after esophageal surgery. We investigated the correlation between
      ICU psychosis and serum melatonin concentration during the period after
      esophagectomy. METHODS: The study group comprised 41 patients who underwent
      esophagectomy for treatment of esophageal cancer between 1999 and 2001. The
      cohort included 36 men and 5 women, aged 36 to 78 years. After surgery, blood
      samples were collected 4 times a day for 4 days. Serum levels of melatonin were
      determined with a melatonin radioimmunoassay kit. The regularity of the melatonin
      circadian rhythm pattern, as defined by the frequency of occurrence of the peak
      level of melatonin secretion, was determined (the pattern was described as
      irregular at less than 3 times in the measurement period). RESULTS: Of the 41
      patients who met the inclusion criteria, 11 (26.8%) had ICU psychosis develop.
      These patients were older than those patients in whom ICU psychosis did not
      develop (P =.01). No significant differences were seen in the duration of
      surgery, volume of blood loss, term in the ICU, term of intubation, tumor
      location, disturbances of organ function, and postoperative complications between
      patients in whom ICU psychosis developed, and those patients in whom it did not.
      Patients with ICU psychosis tended to have abnormally low serum levels of
      melatonin. Of the 41 patients studied, 9 (22%) had an irregular pattern of
      melatonin circadian rhythm. A significant correlation was seen between ICU
      psychosis and an irregular melatonin circadian rhythm (P =.0001). CONCLUSION:
      Irregular patterns of melatonin circadian rhythm may be associated with ICU
      psychosis. Supplementation with melatonin, or acceleration of melatonin
      secretion, may protect patients from development of ICU psychosis and may promote
      recovery to a normal mental state.

PMID- 12796736
TI  - Total vascular exclusion of the liver enhances the efficacy of retroviral
      mediated associated thymidine kinase and interleukin-2 genes transfer against
      multiple hepatic tumors in rats.
AB  - BACKGROUND: Recent advances in gene transfer technology render gene therapy an
      attractive treatment of disseminated liver metastases for which other treatments
      remain disappointing. In this setting, total vascular exclusion of the liver
      could improve gene transfer to cancer cells and prevent extrahepatic vector
      spreading during portal infusion of therapeutic genes. We evaluate the efficiency
      of combined herpes simplex virus type-1 thymidine kinase (HSV1-TK) and
      interleukin-2 retrovirus-mediated gene transfer through the portal vein, under
      total vascular exclusion of the liver, in a model of macroscopic multiple liver
      metastases in rats. METHODS: Multifocal liver metastases were established in BDIX
      rats with intraportal injection of DHDK12 colon cancer cells. On randomization,
      rats received either vector-producing cells or saline solution under total
      vascular exclusion of the liver. Vector-producing cells released retroviral
      vectors encoding Lac-Z in marking studies or HSV1-TK or interleukin-2 in
      therapeutic studies. Rats were either killed for pathologic studies, or followed
      for survival. RESULTS: Total vascular exclusion of the liver markedly improved
      gene transfer efficacy in marking studies. In therapeutic studies we observed a
      significant reduction in tumor volume of treated rats compared with untreated
      controls (2170 +/- 310 mm(3)). Although singular HSV1-TK or interleukin-2 gene
      transfer showed significant efficacy, the greatest tumor volume regression was
      observed in rats treated with combined HSV1-TK + interleukin-2 gene therapy (145
      +/- 60 mm(3); P =.0001 vs control). This translated into an increased median
      survival rate compared with either control rats (P =.006) or rats treated with
      single gene therapy. CONCLUSION: In a rat model, a significant antitumoral effect
      against macroscopic multifocal liver metastases can be observed after retrovirus
      mediated HSV1-TK and interleukin-2 gene transfer through the portal vein under
      total vascular exclusion of the liver, followed by ganciclovir administration. We
      believe that this well-tolerated and efficient therapeutic approach deserves
      clinical evaluation in patients with disseminated colorectal liver metastases.

PMID- 12796738
TI  - Cystosarcoma phyllodes (phyllodes tumor) of the male breast.

PMID- 12796737
TI  - Pancreatic elastase is proven to be a mannose-binding protein--implications for
      the systemic response to pancreatitis.
AB  - BACKGROUND: Mannose-binding proteins (MBPs) have been isolated from serum, liver,
      lung, and kidney and are believed to play an important role in first-line host
      defense during acute phase inflammatory response. Because of the inflammatory
      nature of pancreatitis, we postulate that the pancreas produces endogenous MBP.
      METHODS: Pancreatic juice, from both human and rat, was collected by pancreatic
      duct cannulation and subjected to mannose-Sepharose affinity chromatography to
      isolate pancreatic MBP (pMBP). Protein eluates from the mannose-Sepharose column
      were analyzed using reverse-phase high-performance liquid chromatography, sodium
      dodeclysulfate-polyacrylamide gel electrophoresis, and, subsequently, by N
      terminal protein sequencing. Western blot analysis was used to identify the pMBP,
      and reverse transcriptionase-polymerase chain reaction was used to examine its
      mRNA expression. Complement lysis was measured using red blood cells coated with
      yeast mannan. Tumor necrosis factor (TNF)-alpha mRNA expression in macrophages
      was measured using RNase protection assay. RESULTS: A 30-kd MBP was isolated from
      both human and rat pancreatic juice and a rat acinar cell line. Genetic analysis
      (using RT-PCR with known MBP primers) and protein analysis (using Western blot
      with a known anti-MBP antibody) suggest that the pMBP is different from any
      previously described MBP. Protein sequencing analysis of pMBP generated an N
      terminus sequence of 12 residues, indicating that pMBP is human pancreatic
      elastase III. Western blot analysis using an anti-elastase antibody confirms that
      the pMBP is a pancreatic elastase. Exposure of macrophages to pancreatic elastase
      resulted in an increased mRNA level of TNF-alpha, a potent proinflammatory
      cytokine in acute-phase response. Addition of mannan to pancreatic elastase
      further upregulated the TNF-alpha response. CONCLUSION: We isolated an MBP from
      the pancreas and identified it as pancreatic elastase. We characterized it as
      having properties different from that of any previously known MBP. We showed that
      pMBP or pancreatic elastase is involved in the activation of macrophages, and
      that this activation is potentiated by mannan. We postulate that the mannose
      binding properties of pancreatic elastase identify this enzyme as a candidate
      catalyst for both pancreatic and systemic inflammation.

PMID- 12796739
TI  - Withdrawal of operative consent.

PMID- 12796740
TI  - Those were the days.

PMID- 12796741
TI  - Rethinking the watchful waiting approach to the swallowed coin problem.

PMID- 12796742
TI  - Osteoclast-like giant cell tumor of the pancreas associated with a mucinous
      cystadenocarcinoma.

PMID- 12796743
TI  - Supplemental perioperative fluid administration increases tissue oxygen pressure.

PMID- 12796744
TI  - Atheromatous showers, periprocedural myocardial infarction, and fatality.

PMID- 12796745
TI  - Impacting the use of the screening electrocardiogram.

PMID- 12796746
TI  - Atropine for inconclusive exercise tests: a beautiful solution or just cosmetics?

PMID- 12796747
TI  - Markers of inflammation and thrombosis: clues to plaque instability?

PMID- 12796748
TI  - Detection of endothelial dysfunction with brachial artery ultrasound scanning.
AB  - The role of the endothelium in human disease recently has become the focus of
      intense scientific investigation. Impaired endothelial function is associated
      with a number of disease states, including cardiovascular disease (CVD) and its
      major risk factors. Endothelial dysfunction precedes overt vascular disease by
      years and may itself be a potentially modifiable CVD risk factor. Although no
      gold standard for the measurement of endothelial function exists, the measurement
      of flow-mediated dilation (FMD) in the brachial artery, assessed with Doppler
      ultrasonography, is the most studied method and shows the most promise for
      clinical application. It is a well-tolerated, noninvasive, and low-risk
      procedure. Brachial artery FMD after transient vascular occlusion may serve as an
      index of nitric oxide bioavailability, and its impairment correlates with
      coronary arterial abnormalities. These factors, with the wide availability of
      vascular ultrasound scanning in clinical practice, make brachial artery FMD an
      attractive screening tool for endothelial dysfunction. Present limitations of
      this procedure include the lack of a consensus definition of normal FMD and the
      variability among centers in both procedural technique and image analysis.
      However, these limitations are likely to be overcome with increasing experience
      and advances in technology, and with further refinements, the measurement of
      brachial artery FMD will likely become the clinical technique of choice for the
      evaluation of endothelial disease.

PMID- 12796749
TI  - Role of single photon emission computed tomography imaging in the evaluation of
      therapy for angina pectoris.

PMID- 12796750
TI  - High levels of circulating endothelial microparticles in patients with acute
      coronary syndromes.
AB  - BACKGROUND: Endothelial injury plays a critical role in coronary artery disease
      (CAD), but the assessment of this injury has been problematical. Recently, it has
      been shown in vitro that endothelial cells (ECs) release endothelial
      microparticles (EMPs) on activation or apoptosis and that an assay of EMPs can
      provide useful information on EC status in patients with thrombotic disorders.
      This study is aimed at assessing possible correlations between EMPs, which are
      markers of endothelial injury, and clinical subgroups of patients with CAD.
      METHODS: A prospective, case-controlled study was conducted on 84 patients with
      CAD and 42 control subjects to investigate EMP profiles. Included were 64
      patients with acute coronary syndromes ([ACS], 38 with myocardial infarction [MI]
      and 26 with unstable angina [UA]) and 20 patients with stable angina (SA). EMPs
      in platelet-poor plasma were measured flow cytometrically with combinations of
      fluorescent antibodies (anti-CD31, -51, -42), allowing distinction of EMPs from
      platelet microparticles (PMPs). Clinical subgroups of patients were correlated
      with EMP and PMP levels in blood. RESULTS: Two species of EMPs (CD31+ and CD51+)
      were evaluated. Both were significantly higher in patients with CAD than in
      control subjects. CD31+ EMP was higher in ACS than SA. Among patients with first
      MI, CD31+ EMP was higher in patients with MI than in patients with UA and was
      significantly higher than in patients with recurring MI. CD51+ EMP did not
      discriminate ACS from SA. A simultaneous assay of PMP showed correlation between
      EMPs and PMPs. However, PMPs did not discriminate patients with SA from control
      subjects. CONCLUSIONS: EMP assay appears promising for assessing EC injury in
      CAD.

PMID- 12796751
TI  - What is the role for improved long-term antiplatelet therapy after percutaneous
      coronary intervention?
AB  - BACKGROUND: Coronary stent placement has replaced balloon angioplasty as the
      percutaneous coronary intervention (PCI) method of choice, primarily because of
      its lower restenosis rate. Compared with aspirin (ASA) monotherapy or ASA plus
      warfarin, the ticlopidine and ASA combination is superior in reducing thrombotic
      events after stenting. Clopidogrel plus ASA appears to be at least as effective
      as ticlopidine and ASA. Intravenous glycoprotein IIb/IIIa inhibitors effectively
      prevent periprocedural thrombotic complications, but their short duration of
      action and parenteral dosing don't allow for long-term protection. This review
      aimed to answer how long after PCI with a stent patients are at risk for
      recurrent thrombotic events and what the optimal way to prevent them is. RESULTS:
      Classically, ASA has been prescribed indefinitely, whereas adenosine diphosphate
      receptor antagonists have been discontinued after 2 to 4 weeks. However, the
      Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found
      that long-term dual antiplatelet therapy with clopidogrel and ASA was more
      effective than ASA alone in preventing major cardiovascular events in patients
      with acute coronary syndrome, including those treated with PCI. CONCLUSION:
      Results from additional ongoing studies are needed to clarify the role of long
      term dual oral antiplatelet therapy in preventing ischemic events in patients who
      have undergone PCI.

PMID- 12796752
TI  - Feedback intervention to reduce routine electrocardiogram use in primary care.
AB  - BACKGROUND: Although physicians frequently order non-essential diagnostic tests,
      including screening tests such as electrocardiograms (ECGs), effective strategies
      for achieving evidence-based test-ordering are not proven. Our objective was to
      evaluate the impact of a feedback intervention designed to reduce the rate of
      screening ECG use and its variation. METHODS: A non-randomized pre-post
      intervention trial assessed the ordering of ECGs among primary care providers
      affiliated with Massachusetts General Hospital. Among outpatients visiting
      providers, those with cardiac diagnoses or symptoms were excluded, as were
      providers with <120 annual visits. Data were available on 117 providers, 105,682
      patients, and 511,328 patient visits. During a 9-month intervention, providers
      received periodic case-mix-adjusted peer-comparisons of their screening ECG use.
      Two computerized billing systems tracked baseline (December 1996 to March 1998),
      intervention (April 1998 to December 1998), and post-intervention (January 1999
      to September 1999) ECG use. Our outcome measures were: 1) the likelihood of ECG
      ordering at office visits and 2) provider practice variation, indicated by
      coefficient of variation and interquartile range. RESULTS: ECGs were ordered in
      4.6% of visits before the intervention. Provider variation in case-mix adjusted
      ECG ordering was substantial (coefficient of variation, 101.6%; interquartile
      range, 3.2% [1.5%-4.7%]). ECG ordering averaged 3.5% during the intervention and
      2.8% post-intervention (P <.001). Variation in ECG ordering narrowed considerably
      (coefficient of variation, 92.5%; interquartile range, 2.0% [1.0%-3.0%]) after
      the intervention. Multivariate analysis confirmed a persistent impact of the
      intervention. CONCLUSIONS: Feedback to primary care providers successfully
      reduced ECG use and its variation. This approach may be applicable to other
      physician behaviors that remain contrary to evidence, but are not questioned
      because peer comparisons are unavailable.

PMID- 12796753
TI  - Prediction of Recurrent Events by D-Dimer and Inflammatory Markers in Patients
      with Normal Cardiac Troponin I (PREDICT) Study.
AB  - BACKGROUND: The independent predictive value of d-dimer and inflammatory markers
      for the risk of recurrent adverse events in patients with acute chest pain but
      normal levels of cardiac troponin I (cTnI) remains unclear. METHODS: We studied
      391 patients admitted to the hospital in 1 year with acute ischemic-type chest
      pain. Creatine kinase-myocardial band isoenzyme (CK-MB) mass and cTnI levels were
      measured in initial and 12-hour samples. Soluble intercellular adhesion molecule
      (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, sP-selectin, sE-selectin,
      high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), fibrinogen, and
      d-dimer levels were measured in initial samples. A 1-year incidence of death,
      myocardial infarction (MI), revascularization, or readmission with chest pain was
      determined (with death/MI as the primary end point). RESULTS: Patients with
      normal levels of CK-MB(mass) and cTnI (195/391[50%]) were at a lower risk than
      patients with elevated levels of CK-MB(mass) or cTnI, but still had an important
      incidence of events (77/195[39%]). Marker elevation was defined as >75th
      percentile (upper quartile). Elevated d-dimer levels (>580 ng/mL) was predictive
      of death/MI (odds ratio, 5.4; 95% CI, 1.5-20.2; P =.005). Elevated sP-selectin
      levels (>152 ng/mL; odds ratio, 3.2; 95% CI, 0.9-11.6; P =.06) trended to
      increased death/MI rates, with weaker trends for elevated levels of hsCRP (>7.1
      mg/L), IL6 (>10.7 pg/mL), and ST depression. Other markers, other
      electrocardiogram changes, or classic risk factors were not predictive of
      death/MI. With a multivariate analysis, d-dimer and sP-selectin were found to be
      of independent significance for death/MI after adjustment for inflammatory,
      hemostatic, and electrocardiogram markers and d-dimer after adjustment for
      classic risk factors. CONCLUSION: Normal cTnI levels after acute chest pain does
      not confer absence of future risk. Concurrent assessment of d-dimer and
      inflammatory markers may improve risk stratification.

PMID- 12796754
TI  - Differential effects of antihypertensive agents on electrocardiographic voltage:
      results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial.
AB  - BACKGROUND: Serial decline in electrocardiographic voltage in patients with
      increased left ventricular mass has been associated with a lower risk of
      cardiovascular events. METHODS: We studied 468 patients with diabetes mellitus
      and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD)
      trial. Patients were randomized in a stratified design to receive initial
      treatment with either enalapril or nisoldipine and to either intensive or
      moderate treatment goals. We measured an electrocardiographic index for increased
      left ventricular mass, the adjusted Cornell voltage, serially by treatment group.
      The association between changes in electrocardiographic voltage and
      cardiovascular events was defined with Cox proportional hazards analysis.
      RESULTS: In 5 years of follow-up, the decline in adjusted Cornell voltage was
      significantly greater for patients treated with enalapril than for patients
      treated with nisoldipine (repeated measures analysis of variance P =.002). In the
      Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine)
      was the strongest predictor of cardiovascular events, but the presence of
      coronary disease at baseline, the duration of diabetes mellitus, and change in
      voltage were also independent predictors of cardiovascular events. CONCLUSIONS:
      In the ABCD study, enalapril treatment was associated with a lower risk of
      myocardial infarction. The reduction in left ventricular mass as reflected by
      diminished electrocardiographic voltage may explain some, but not all, of the
      effect of enalapril in this study.

PMID- 12796755
TI  - Apolipoprotein E genotype is not associated with cardiovascular disease in
      heterozygous subjects with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder
      characterized by high low-density lipoprotein cholesterol levels and premature
      cardiovascular disease (CVD). There are important differences in the presence of
      CVD among heterozygous subjects with FH. Some of this variability can be
      explained by genetic factors, and the apolipoprotein (apo) E genotype has been
      proposed as a useful marker. METHODS: We analyzed the apo E genotype in 706 non
      related subjects who were heterozygous for FH from Spain. CVD was present in 198
      subjects (28%), 132 men (41%) and 66 women (17%). RESULTS: Apo E allele
      frequencies for the epsilon 3, epsilon 4, and epsilon 2 alleles were 0.89, 0.09,
      and 0.02 respectively. Age, body mass index, smoking status, high blood pressure,
      diabetes mellitus, presence of tendon xanthomas, total cholesterol level,
      triglyceride levels, high-density lipoprotein cholesterol level, low-density
      lipoprotein cholesterol level, and Lp(a) did not differ among genotypes. The
      incidence of CVD and the age of onset of CVD did not differ among genotypes
      either. In the multivariant analysis, apo E genotype did not contribute
      significantly to CVD. CONCLUSIONS: Heterozygous men with FH have a very high risk
      of coronary disease in a Mediterranean country, and the apo E genotype in this
      large group of adults with FH is not associated either with CVD or lipid values,
      in contrast with the established effect in the general population.

PMID- 12796756
TI  - Prognostic implication of creatine kinase release after elective percutaneous
      coronary intervention in the pre-IIb/IIIa antagonist era.
AB  - BACKGROUND: The significance of mild elevations in cardiac enzymes after an
      elective percutaneous coronary intervention (PCI) still remains controversial. We
      evaluated the significance of creatine phosphokinase level (CPK) elevations in a
      large cohort of patients who had undergone an elective PCI before the IIb/IIIa
      receptor antagonist era. METHODS: All patients enrolled in the Emory databank
      from 1981 to 1996 who had an elective PCI were evaluated. We identified 15,637
      patients who met our inclusion and exclusion criteria. Patients were divided into
      4 groups on the basis of the magnitude of the CPK elevation noted in the post-PCI
      period: group I (CPK <250 mg/dL, n = 14,512); group II (CPK 250-500 mg/dL, n =
      715); group III (CPK 500-750 mg/dL, n = 164); and group IV (CPK >750 mg/dL, n =
      246). RESULTS: CPK elevations were associated with a significant increase in the
      periprocedure angiographic complications. Angiographic complication rates were
      14.6%, 30.5%, 40.2%, and 43.5% in groups I, II, III, and IV, respectively (P
      <.001). Long-term survival also correlated inversely with the magnitude of CPK
      elevations. The 10-year survival rates were 73%, 71%, 69%, and 55% in groups I,
      II, III, and IV, respectively (P <.0001). After multivariate analysis to correct
      for clinical factors, a CPK elevation of at least 3-times normal (group IV) was
      found to be an independent predictor of diminished 30-day and long-term survival
      (hazard ratio 1.84, 95% CI 1.41-2.41, P <.0001). Elevations in CPK <3-times
      normal (groups II and III) were not independently predictive of poor long-term
      survival. CONCLUSION: A CPK level >3-times normal after an elective PCI is a
      strong independent predictor of poor long-term prognosis.

PMID- 12796757
TI  - Predictors of angiographic restenosis after coronary intervention in patients
      with diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus are particularly prone to restenosis
      after percutaneous coronary intervention. An exploratory, nested, case-control
      study was undertaken to identify clinical, lesional, and procedural predictors of
      angiographic restenosis in these patients. METHODS: Seventy-five patients with
      diabetes mellitus with 86 coronary lesions were selected from a larger population
      of 217 patients who had undergone 6-month angiographic follow-up after a first,
      successful balloon angioplasty (PTCA) or stent implantation procedure. Data
      collection was by patient interview and review of hospital database and other
      medical records. All angiograms were analyzed with quantitative coronary
      angiography, and restenosis was defined as a >or=50% diameter reduction at the
      treated site. A multivariate analysis of 10 prespecified explanatory variables,
      derived from a literature review, was performed on a per-lesion basis. RESULTS:
      There were 45 patients (53 lesions) with restenosis and 30 patients (33 lesions)
      without restenosis. Univariate predictors of binary restenosis were
      periprocedural glycosylated hemoglobin level, vessel reference diameter, PTCA,
      and larger final balloon size to reference artery diameter ratio. Multiple
      logistic regression identified poor glycemic control (odds ratio [OR] 3.03, 95%
      CI 1.06-8.65, P =.038), small vessel reference diameter (OR 3.41, 95% CI 1.17
      9.95, P =.025), and mode of intervention (OR 3.12, 95% CI 1.08-9.00, P =.036) as
      independent risk factors. Vessel reference diameter appeared to be an important
      effect modifier of the association between type of intervention and angiographic
      outcome, with stenting no longer superior to PTCA in patients with diabetes
      mellitus who had vessels <2.87 mm in diameter (P =.054). CONCLUSION: Poor
      glycemic control, vessel size, and PTCA were independent predictors of restenosis
      in patients with diabetes mellitus. It is possible that improved periprocedural
      glycemic control, in addition to stenting, may reduce the restenosis rate in
      these patients.

PMID- 12796758
TI  - Predicting vascular complications in percutaneous coronary interventions.
AB  - OBJECTIVES: Using a large, current, regional registry of percutaneous coronary
      interventions (PCI), we identified risk factors for postprocedure vascular
      complications and developed a scoring system to estimate individual patient risk.
      BACKGROUND: A vascular complication (access-site injury requiring treatment or
      bleeding requiring transfusion) is a potentially avoidable outcome of PCI.
      METHODS: Data were collected on 18,137 consecutive patients undergoing PCI in
      northern New England from January 1997 to December 1999. Multivariate regression
      was used to identify characteristics associated with vascular complications and
      to develop a scoring system to predict risk. RESULTS: The rate of vascular
      complication was 2.98% (541 cases). Variables associated with increased risk in
      the multivariate analysis included age >or=70, odds ratio (OR) 2.7, female sex
      (OR 2.4), body surface area <1.6 m(2) (OR 1.9), history of congestive heart
      failure (OR 1.4), chronic obstructive pulmonary disease (OR 1.5), renal failure
      (OR 1.9), lower extremity vascular disease (OR 1.4), bleeding disorder (OR 1.68),
      emergent priority (OR 2.3), myocardial infarction (OR 1.7), shock (1.86), >or=1
      type B2 (OR 1.32) or type C (OR 1.7) lesions, 3-vessel PCI (OR 1.5), use of
      thienopyridines (OR 1.4) or use of glycoprotein IIb/IIIa receptor inhibitors (OR
      1.9). The model performed well in tests for significance, discrimination, and
      calibration. The scoring system captured 75% of actual vascular complications in
      its highest quintiles of predicted risk. CONCLUSION: Predicting the risk of post
      PCI vascular complications is feasible. This information may be useful for
      clinical decision-making and institutional efforts at quality improvement.

PMID- 12796759
TI  - Effects of amlodipine on ischemia after percutaneous transluminal coronary
      angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis
      (CAPARES) Study.
AB  - BACKGROUND: Despite successful coronary angioplasty (PTCA), patients may have
      ischemia after the procedure because of the overall coronary disease and luminal
      renarrowing at the lesion sites. The aim of this study was to examine the effects
      of the calcium-channel blocker amlodipine on post-PTCA ischemia. METHODS: In a
      prospective, double-blind design, patients were randomized to receive 10 mg of
      amlodipine or placebo 2 weeks before angioplasty. Exercise tests and 48-hour
      ambulatory electrocardiography recordings were performed in 405 patients, 2 weeks
      before and 2 and 20 weeks (early and late) after PTCA. RESULTS: There were no
      differences in clinical and angiographic baseline characteristics between the
      treatment groups. Ischemia and angina were equally distributed before PTCA, and
      no difference in restenosis was found between the groups at follow-up. The
      incidence of angina was significantly lower in the amlodipine group compared with
      the placebo group both early and late after PTCA (P =.04 and.03). Exercise
      induced ischemia was reduced by 40% (P =.009) early and 34% (P =.02) late after
      PTCA in the amlodipine group, and ischemia on ambulatory electrocardiography was
      reduced by 18% early and 28% late after PTCA compared with placebo (P =.06 and P
      =.009). CONCLUSION: Ischemia and angina occurred after successful PTCA and were
      significantly reduced by amlodipine.

PMID- 12796760
TI  - Comparison of the dose-response relationships of 2 lipid-lowering agents: a
      Bayesian meta-analysis.
AB  - BACKGROUND: Comparing the dose-response of a new drug to that of a previously
      studied drug can aid in understanding their relative potencies. Two dose-finding
      studies addressed the effect of a new drug, rosuvastatin, on its ability to
      decrease low-density lipoprotein cholesterol (LDL-C) levels. One of these studies
      included 2 doses of atorvastatin, and substantial additional information is
      available in the literature about the effect of atorvastatin on LDL-C level
      lowering. METHODS: The 2 dose-finding studies of rosuvastatin considered
      otherwise healthy patients who had hypercholesterolemia. Comparable studies of
      atorvastatin were identified via a MEDLINE search in December 1999. Multiple
      reviewer consensus identified 15 of 41 studies on atorvastatin published since
      1996 that met these selection criteria: reporting of LDL-C level change from
      baseline at least 6 weeks after treatment initiation, doses administered, and
      treatment group sizes. Eligible populations had clinical evidence of
      hypercholesterolemia. We excluded studies with patients who had severe illness or
      a previous history of transplantation. Data extraction of the mean, sample sizes,
      and SDs (or CIs) by dose was carried out independently by multiple reviewers. We
      combined the results from the various studies with Bayesian hierarchical modeling
      and analyzed them with Markov chain Monte Carlo techniques. RESULTS: Combining
      this study and literature results substantially increased the power to compare
      the dose-response relationships of rosuvastatin and atorvastatin. Rosuvastatin
      reduced LDL-C level by an estimated 10 to 17 percentage points more than
      atorvastatin when both were given at the same dose. Approximately one quarter of
      the dose of rosuvastatin achieved about the same magnitude of LDL-C level
      reduction as atorvastatin at dosages as high as 80 mg. This finding does not
      imply a 4-fold difference in efficacy overall and specifically does not describe
      the results at higher dosage levels. CONCLUSIONS: Bayesian meta-analysis of
      results from related studies allows the comparison of the dose-response
      relationships of 2 drugs, better estimates of a particular dose-response
      relationship within an individual study, and the expression of relative benefits
      (of dose and drug) in terms of probabilities. Explicitly comparing a study's
      results with historical data using Bayesian meta-analysis allows clinicians to
      view the study in the larger context of medical research.

PMID- 12796761
TI  - Use of atropine in patients with chronotropic incompetence and poor exercise
      capacity during treadmill stress testing.
AB  - BACKGROUND: Treadmill stress testing (TMST) is a valuable diagnostic test for
      ischemic heart disease. However, the inability to achieve the target heart rate
      because of either chronotropic incompetence or poor exercise capacity is a major
      limitation to its utility. We evaluated the usefulness of atropine in decreasing
      the number of tests with inconclusive results in patients with a poor
      chronotropic response or exercise capacity during TMST. METHODS: The study
      comprised 126 patients undergoing TMST. In subjects experiencing fatigue at
      submaximal exercise, atropine was administered in doses of 0.5 mg per minute
      until the test conclusion (positive test results or target heart rate achieved)
      or until a maximum dose of 2 mg was administered. RESULTS: Thirty-three of the
      126 patients (26%) required atropine (mean dose, 1 mg) during the study; 23 of
      the 33 patients (70%) proceeded to achieve their target heart rate (n = 17) or
      positive test results (n = 6). The mean increase in heart rate after atropine
      administration was 25 beats/min (range 3-53 beats/min). Atropine was required in
      39% of patients receiving beta-blockers, versus 21% of patients not receiving
      beta-blockers (P =.02). Among patients receiving atropine, a conclusive test was
      achieved significantly more often in patients not receiving beta-blockers (94% vs
      46%, P =.01). No adverse events were associated with the use of atropine.
      Atropine administration resulted in conclusive tests more often in subjects with
      poor chronotropic response than in subjects with poor exercise capacity (78%
      vs33%, P = <.001). CONCLUSION: The use of atropine as an adjunct to standard TMST
      can help decrease the number of inconclusive tests, even in patients taking beta
      blockers. Larger studies are warranted to further define the role of atropine in
      diagnostic TMST.

PMID- 12796762
TI  - Quantitative regional wall motion analysis with early contrast ventriculography
      for the assessment of myocardium at risk in acute myocardial infarction.
AB  - BACKGROUND: Several techniques have been used to quantify the myocardium at risk,
      including measurement of regional ventricular function with contrast
      ventriculography and measurement of perfusion defect size with tomographic
      technetium-99m-sestamibi imaging. This study evaluates the correlation between
      these 2 techniques. METHODS: Twenty-three patients with angiographically
      documented coronary occlusion and acute myocardial infarctions (10 anterior, 13
      inferior) were studied. All patients had contrast left ventriculography at the
      time of their acute angiogram before any revascularization therapy. Regional wall
      motion parameters measured with the centerline method were the severity,
      circumferential extent, and global circumferential extent of hypokinesis and the
      mean standardized motion in predefined areas. Technetium-99m-sestamibi was
      injected before reperfusion therapy with measurement of the myocardium at risk
      using single photon emission computed tomography imaging. RESULTS: The
      tomographic sestamibi-measured myocardium at risk was significantly greater for
      anterior infarctions compared with inferior infarctions (40% +/- 18% vs 14.0 +/-
      8.5%, P =.0001). The only parameter of regional wall motion to show a significant
      difference by infarct location was global circumferential extent of hypokinesis
      (43% +/- 25% vs 22% +/- 15%, P =.02). The other parameters were not significantly
      different between anterior and inferior myocardial infarctions. For anterior
      infarctions, these parameters of regional wall motion correlated with myocardium
      at risk assessed with sestamibi: global circumferential extent of hypokinesis (r
      =.88, P <.01), circumferential extent of hypokinesis (r =.78, P <.01), mean
      standardized motion in predefined areas (r = -.74, P <.05), and severity of
      hypokinesis (r = -.70, P <.05). For inferior infarctions, there was no
      significant correlation between any of these parameters of regional wall motion
      and myocardium at risk assessed with sestamibi imaging. CONCLUSION: The
      assessment of regional ventricular function with contrast ventriculography
      correlates with the area of myocardium at risk measured with tomographic
      technetium-99m-sestamibi for anterior, but not for inferior, myocardial
      infarctions. Therefore, these parameters of regional wall motion are a poor
      measure of the efficacy of reperfusion therapies.

PMID- 12796763
TI  - Mitral valve repair and replacement in northern New England.
AB  - BACKGROUND: The etiology of mitral valvular disease has changed in the last 20
      years, and new techniques for the diagnosis and repair of mitral valves have been
      advanced. A retrospective regional study was conducted to identify changes in
      patient and disease characteristics and in population-based rates for mitral
      valve repair and replacement in northern New England. METHODS: Data from 1648
      patients were collected from 5 clinical centers in Maine, New Hampshire, and
      Vermont between January 1, 1990, and December 31, 1999. U.S. Census data were
      used to calculate population-based rates. RESULTS: Total mitral valve procedures
      increased 2.4 times, from 8.7 to 20.6 cases/100,000/year (p(trend) = 0.004).
      Primary procedures increased from 6.7 to 16.9 cases/100,000/year (p(trend) =
      0.014). Primary mitral valve repair procedures increased 3.7 times, from 2.4 to
      8.9 cases/100,000/year (p(trend) = 0.012), whereas mitral valve replacement
      increased only 1.9 times, from 4.3 to 8.0 cases/100,000/year (p(trend) = 0.016).
      Repeat mitral valve operations did not change significantly (p(trend) = 0.810).
      During this period, there was a significant increase of the percentage of
      octogenarians (p(trend) = 0.016) and of patients with ejection fractions <40%
      (p(trend) = 0.012). There was a decrease in the percentage of patients with
      mitral stenosis (p(trend) = 0.024). CONCLUSION: In an era of a change in the
      etiology of mitral valvular disease and new techniques for diagnosis and repair
      of mitral valvular disease, regional data demonstrate substantial increased rates
      of mitral repair and replacement and expanded indications of older age and poorer
      left ventricular function.

PMID- 12796764
TI  - Outcomes of uncomplicated aortic valve stenosis presenting in infants.
AB  - BACKGROUND: The management of uncomplicated aortic valve stenosis presenting with
      critical obstruction in infants continues to be associated with significant
      morbidity and mortality. However, not all infants have critical obstruction, and
      outcomes spanning the broader spectrum of disease severity are less well defined.
      METHODS: In a 12-year period, 55 infants (<3 months of age) were seen with aortic
      valve stenosis and with anatomy suitable for biventricular repair. Clinical,
      echocardiographic, angiographic, management, and outcome data were reviewed.
      RESULTS: Status at presentation (median age 6 days) included signs of congestive
      heart failure in 20 patients, cardiovascular collapse in 5 patients, and an
      asymptomatic heart murmur in 30 patients. The initial echocardiogram showed
      reduced left ventricular function in 26% of patients, with a mean peak
      instantaneous gradient of 69 +/- 30 mm Hg in patients with normal function. There
      were 5 deaths (9%), all in patients with poor ventricular function. The initial
      intervention was balloon valvotomy in 24 patients and surgical valvotomy in 20
      patients, with 11 patients having no intervention to date. The freedom-from
      intervention rate was 69% at age 1 week, 58% at 1 month, 36% at 3 months, and 28%
      at 1 year. Patients without cardiovascular collapse, normal left ventricular
      function, and gradients <60 mm Hg at presentation (n =1 9) had better survival
      and longer freedom from intervention than patients with poor ventricular function
      or gradients >or=60 mm Hg (n = 36, P =.0001). CONCLUSION: Most infants with
      aortic valve stenosis receive intervention, although this may be safely delayed
      in selected patients with lower initial gradients and good left ventricular
      function.

PMID- 12796765
TI  - Associations of aortic and mitral regurgitation with body composition and
      myocardial energy expenditure in adults with hypertension: the Hypertension
      Genetic Epidemiology Network study.
AB  - BACKGROUND: It has been reported that aortic regurgitation, mitral valve
      regurgitation, or both are associated with lower body mass index, an index of
      body adiposity. However, the relations of valvular regurgitation to body
      composition and myocardial bioenergetic expenditure have not been previously
      investigated in a population-based sample. METHODS: We selected 1496 patients
      with hypertension who did not have diabetes mellitus to participate in the
      Hypertension Genetic Epidemiology Network (HyperGEN) study. We excluded
      participants with severe aortic or mitral stenosis or with known coronary heart
      disease. Bioimpedance was used to assess body composition. Echocardiography was
      used to assess left ventricular (LV) structure and function and to calculate
      myocardial workload (expressed as energy expenditure) from end-systolic stress,
      ejection time, and stroke volume. The study sample was divided into groups
      without mitral or aortic regurgitation (control subjects, n = 1175), with mild
      valvular regurgitation (1+, n = 246), and with at least moderate (>or=2+) mitral
      or aortic regurgitation (n = 75). RESULTS: The mean patient age was higher with
      more severe valvular insufficiency. Sex distribution and blood pressure were
      similar among the 3 groups. Body mass index and fat mass were significantly lower
      with more severe valvular regurgitation, whereas fat-free mass was only slightly
      lower in the group with >or=2+ regurgitation compared with control subjects.
      Skinfold thicknesses (brachial and subscapular) were lower with more severe
      valvular regurgitation, whereas self-reported physical activity per week was
      similar among the 3 groups. LV mass and circumferential end-systolic stress were
      higher with more severe valvular regurgitation. Noninvasively estimated
      myocardial energy expenditure was slightly higher in participants with 1+
      valvular regurgitation and was significantly higher with >or=2+ regurgitation.
      Ejection fraction was mildly lower with >or=2+ aortic insufficiency, mitral
      insufficiency, or both. Midwall shortening and stress-corrected midwall
      shortening did not differ among groups. CONCLUSIONS: In a population-based sample
      of adults with hypertension and without diabetes mellitus, known coronary heart
      disease, or significant valvular stenosis, mitral and aortic regurgitation were
      associated with higher LV mass and total myocardial biomechanical workload but
      with lower body fat mass and slightly lower body fat-free mass, which suggests
      that global myocardial bioenergetic expenditure is elevated by concomitant
      valvular regurgitation beyond the effect of pressure overload caused by
      hypertension.

PMID- 12796766
TI  - Compared with control subjects, the systemic sympathetic nervous system is
      activated in patients with mitral regurgitation.
AB  - BACKGROUND: Whether the systemic sympathetic nervous system is activated as a
      compensatory mechanism in response to mitral regurgitation (MR) in humans is
      unknown. We tested the hypotheses that the systemic sympathetic nervous system
      would be activated in patients with MR in comparison with control subjects and
      that this activation would occur early in the disease process as a compensatory
      mechanism for chronic left ventricular (LV) volume overload. METHODS: We studied
      37 patients with MR who underwent right heart catheterization and biplane
      cineventriculography to obtain LV end-diastolic and end-systolic volumes,
      ejection fractions, and regurgitant volumes. In these 37 patients with MR and in
      23 control subjects, an [(3)H]-norepinephrine ([(3)H]-NE) infusion and multiple
      arterial blood samples provided data for a 2-compartment modeling analysis to
      calculate extravascular NE release rates (NE(2)). RESULTS: The mean NE(2) (2.05
      +/- 0.76 microg/min/m(2)) in the patients with MR was greater than that in the
      control subjects (1.48 +/- 0.75 microg/min/m(2), P =.007). Furthermore, the mean
      NE(2) values were also greater in the patients with MR who were in clinical class
      I (P =.05), with a pulmonary capillary wedge pressure <12 mm Hg (P =.05) or a LV
      ejection fraction >or=0.60 (P =.06) compared with the control subjects. The mean
      NE(2) values were increased further in patients with MR who had a LV ejection
      fraction <0.60 (P =.02). CONCLUSIONS: The systemic sympathetic nervous system is
      activated in patients with MR in comparison with control subjects, and this
      activation appears to occur early in the disease process as a compensatory
      mechanism for LV volume overload.

PMID- 12796767
TI  - Association of consultation between generalists and cardiologists with quality
      and outcomes of heart failure care.
AB  - BACKGROUND: The appropriate roles for generalists and cardiologists in the care
      of patients with heart failure (HF) are unknown. The objective of this
      retrospective cohort study was to determine whether consultation between
      generalists and cardiologists was associated with better quality and outcomes of
      HF care. METHODS: We studied left ventricular function evaluation (LVFE) and
      angiotensin-converting enzyme inhibitor (ACEI) use and 90-day readmission and 90
      day mortality rates in patients with HF who were hospitalized. Patient care was
      categorized into cardiologist (solo), generalist (solo), or consultative cares.
      The processes and outcomes of care were compared by care category using logistic
      regression analyses fit with generalized linear mixed models to adjust for
      hospital-related clustering. RESULTS: Of the 1075 patients studied, 13% received
      cardiologist care, 55% received generalist care, and 32% received consultative
      care. More patients who received consultative care (75%) received LVFE than
      patients who received generalist care (36%) and cardiologist care (53%; P <.001).
      Fewer patients who received solo care (54% each) received ACEI compared with 71%
      of patients who received consultative care (P <.001). After multivariable
      adjustment, consultative care was associated with higher odds of LVFE than
      generalist care (adjusted odds ratio [OR], 6.06; 95% CI, 3.97-9.26) or
      cardiologist care (adjusted OR, 2.96; 95% CI, 1.70-5.13) care. Consultation was
      also associated with higher odds of ACEI use compared with generalist (adjusted
      OR, 2.42; 95% CI, 1.42-4.12) or cardiologist (adjusted OR, 2.32; 95% CI, 1.14
      4.72) care. Compared with patients who received generalist care, patients who
      received consultative care had lower odds of 90-day readmission (adjusted OR,
      0.54; 95% CI, 0.34-0.86). CONCLUSION: Collaboration between generalists and
      cardiologists, rather than solo care by either, was associated with better HF
      processes and outcomes of care.

PMID- 12796768
TI  - C-reactive protein in acute myocardial infarction: association with heart
      failure.
AB  - BACKGROUND: High C-reactive protein (CRP) levels have been associated with higher
      mortality rate in patients with acute myocardial infarction (AMI). However, it is
      not known whether inflammation plays a role in the time-course of heart failure
      (HF) in this clinical setting. Our aim was to study the nature of the
      relationship between CRP and HF during AMI. METHODS: This prospective study was
      carried out in 269 subjects admitted to the hospital for suspected AMI. Of these,
      220 had evidence of AMI. The other 49 subjects were studied as controls. CRP was
      assessed on the first, third, and seventh day after admission. RESULTS: CRP was
      significantly higher in the patients with AMI than in the control patients (P
      =.001) and peaked on the third day. Among the patients with AMI, CRP was higher
      in patients with HF than in patients without HF (adjusted P =.008, P =.02 and P
      =.03 on 1st, 3rd, and 7th day, respectively). Prevalence of HF on admission was
      slightly higher in the subjects with first-day CRP >or=15 mg/L than in those with
      CRP <15 mg/L, and the between-group difference progressively increased from the
      first to the seventh day (P <.0001). At multivariable regression analysis, first
      day log-CRP was shown to be a strong independent predictor of both HF progression
      (P <.0001) and left ventricular ejection fraction (P <.0001). One-year total
      mortality and HF-mortality rates turned out to be higher in the patients with CRP
      >or=85 mg/L than in those with CRP below that level (P <.0001), and log-third-day
      CRP was independently associated with 1-year mortality at multivariable analysis
      (P =.0001). CONCLUSIONS: CRP on admission to hospital is suitable for predicting
      the time-course of HF in patients with AMI. Peak CRP value is a strong
      independent predictor of global and HF-mortality during the following year.

PMID- 12796769
TI  - Prospective evaluation comparing the effects of enalapril and losartan in left
      ventricular remodeling after acute myocardial infarction.
AB  - BACKGROUND: Previous studies have compared angiotensin receptor blockers and
      angiotensin-converting enzyme inhibitors in patients with heart failure, but
      there are few data about the effect of these drugs regarding left ventricular
      remodeling after myocardial infarction. METHODS: Fifty-two consecutive patients
      with first anterior wall myocardial infarction within 24 hours of evolution were
      randomized to receive enalapril (as much as 20 mg; mean, 14.6 mg), or losartan
      (as much as 50 mg; mean, 48 mg). Left ventricular ejection fraction and
      ventricular volumes were analyzed in 2 serial radionuclide ventriculograpies,
      carried out within 4 days after the infarction (mean, 97.4 +/- 114.2 hours) and
      after 6 months (mean, 177.7 +/- 16.7 days). Ventriculographies were analyzed by a
      single blinded observer. Mainly because of the unexpected large SD values
      obtained, the power of the study to demonstrate equivalence between the groups
      was only 15.7%. RESULTS: The differences obtained between the first and the
      second ventriculographies, for the enalapril and losartan groups, were: for left
      ventricular ejection fraction, -0.4% +/- 6.6% versus -1.1% +/- 5.9% (P =. 67; 95%
      CI, 2.77-4.23); for final systolic volume, 0.07 +/- 7.7 mL/m(2) versus -0.2 +/-
      6.1mL/m(2) (P =. 85; 95% CI, -3.57-4.26); for final diastolic volume -0.7 +/-
      12.1 mL/m(2) versus -3.6 - 9.9 mL/m(2) (P =. 34; 95% CI, -3.22-9.17). CONCLUSION:
      This study, although underpowered, suggests that neither enalapril nor losartan
      was superior as compared with each other for left ventricular remodeling after
      myocardial infarction; however, powerful evidence of equivalence was not
      provided.

PMID- 12796770
TI  - Contribution of peak respiratory exchange ratio to peak VO2 prognostic
      reliability in patients with chronic heart failure and severely reduced exercise
      capacity.
AB  - BACKGROUND: We evaluated the influence of peak respiratory exchange ratio (pRER),
      as an index of effort adequacy, on peak VO2 prognostic reliability in patients
      with chronic heart failure (CHF) and reduced exercise capacity, whose peak VO2
      may be underestimated because of poor patient motivation. METHODS: A
      cardiopulmonary exercise test was performed in 570 patients with CHF (age 60 +/-
      10 years, ejection fraction 26% +/- 7%, New York Heart Association class 2.2 +/-
      0.6), 193 of whom had a peak VO2 that was >10 but <or=14 mL/kg/min (reduced
      exercise capacity) and 80 of whom had a peak VO2 <or=10 mL/kg/min (severely
      reduced exercise capacity). RESULTS: Seventy-eight events (72 cardiovascular
      deaths and 6 status I heart transplantations) occurred during follow-up (19.6 +/-
      14 months). The 2-year survival rate was 69% in patients with a peak VO2 <or=10
      and 83% in patients with a peak VO2 >10 but <or=14 (P <.0001). However, in the
      group of patients with a peak VO2 <or=10, patients who had a pRER >or=1.15 had a
      2-year survival rate of 52%, and this pRER value (but not >or=1, >or=1.05, or
      >or=1.10) was the only independent predictor of the composite end point (chi(2) =
      4.73, P =.03). Conversely, in the group of patients with a peak VO2 <or=10,
      patients who had a pRER value <1.15 had a survival rate of 83%, which was
      comparable with that of the group of patients with a peak VO2 >10 but <or=14.
      CONCLUSION: Patients with CHF and severely reduced exercise capacity should be
      encouraged to exercise to an RER as close as possible to 1.15, to ascertain their
      motivation and ensure their peak VO2 prognostic reliability.

PMID- 12796771
TI  - Low serum magnesium level predicts major adverse cardiac events after coronary
      artery bypass graft surgery.
AB  - BACKGROUND: Despite improved myocardial protection strategies and enhanced
      surgical techniques, mortality after coronary artery bypass graft surgery (CABG)
      remains essentially unchanged. This may be because of the increasing age of
      patients who undergo primary CABG. Magnesium is an important regulator of
      vascular tone, reperfusion injury, and thrombosis. Therefore, we decided to
      investigate the relationship between serum magnesium levels and major adverse
      cardiac events (MACE) after CABG. METHODS: A total of 957 patients undergoing
      primary CABG were prospectively recruited into the Duke Cardiovascular database
      and had daily serum magnesium levels measured. Low magnesium was defined as <1.8
      mmol/L(-1) at any point during the first 8 days after surgery. Adverse events
      were defined as Q-wave infarction or death measured 1 year after surgery. A
      Kaplan-Meier survival analysis was performed, followed by a Cox proportional
      hazards model, to account for other known predictors of adverse events. RESULTS:
      In the low magnesium group, 12.3% of patients had adverse events, compared with
      9.2% of patients in the normal magnesium group. A serum magnesium level <1.8
      mmol/L(-1) decreased the event-free survival rate (2-fold increased risk of death
      or myocardial infarction at 1 year; hazard ratio 2.0, 95% CI 1.19-3.37).
      CONCLUSIONS: We demonstrated a robust relationship between low serum magnesium
      levels after CABG and a 2-fold increased incidence of Q-wave infarction and all
      cause mortality rate as long as 1 year after surgery. This relationship is
      independent of known preoperative and intraoperative predictors of adverse
      outcomes. This study provides a rationale for a randomized controlled trial of
      magnesium therapy during CABG.

PMID- 12796772
TI  - Regional Angiogenesis with Vascular Endothelial Growth Factor (VEGF) in
      peripheral arterial disease: Design of the RAVE trial.
AB  - BACKGROUND: Patients with intermittent claudication caused by infrainguinal
      atherosclerosis have limited pharmacologic options "Therapeutic angiogenesis" is
      a novel treatment approach that seeks to improve perfusion of ischemic limbs by
      the induction of collateral vessel formation. This trial is a phase 2 randomized
      double-blind placebo-controlled proof of concept trial that will use an
      intramuscular adenoviral gene transfer approach of vascular endothelial growth
      factor, 121 isoform (Ad(GV)VEGF(121.10)) to patients with severe IC caused by
      infrainguinal disease. METHODS: This is a phase 2, double-blind, randomized,
      placebo-controlled, dose-finding, multicenter study. Patients with severe
      intermittent claudication caused by infrainguinal atherosclerosis predominantly
      involving the superficial femoral artery confirmed with imaging studies that meet
      inclusion criteria will be stratified on the basis of the presence or absence of
      diabetes mellitus and randomized in a 1:1:1 fashion to low dose (4 x 10(9)
      particle units), high dose (4 x 10(10) particle units), or placebo arms (35-36
      patients per group). Subjects are required to have exercise-limiting IC in the
      index extremity during 2 qualifying exercise treadmill tests, with peak walking
      times between 1 and 10 minutes. A single dose of Ad(GV)VEGF(121.10) will be
      administered as 20 intramuscular injections throughout the area of the lower limb
      requiring collateralization. RESULTS: The primary efficacy parameter for the
      Regional Angiogenesis With Vascular Endothelial Growth Factor (RAVE) trial is the
      change in peak walking time at 12 weeks compared with baseline. The sample size
      is expected to provide an 80% power to detect a difference of 1.5 minutes between
      any of the 2 treatment groups and the placebo group. Secondary efficacy
      parameters include claudication onset time, hemodynamic effects of therapy
      assessed with ankle-brachial index, assessment of physical impairment, and health
      related quality of life as measured with the Walking Impairment Questionnaire and
      SF-36 Health Survey. All randomized patients will also be evaluated for safety.

PMID- 12796773
TI  - Role of PlGF in the intra- and intermolecular cross talk between the VEGF
      receptors Flt1 and Flk1.
AB  - Therapeutic angiogenesis is likely to require the administration of factors that
      complement each other. Activation of the receptor tyrosine kinase (RTK) Flk1 by
      vascular endothelial growth factor (VEGF) is crucial, but molecular interactions
      of other factors with VEGF and Flk1 have been studied to a limited extent. Here
      we report that placental growth factor (PGF, also known as PlGF) regulates inter-
      and intramolecular cross talk between the VEGF RTKs Flt1 and Flk1. Activation of
      Flt1 by PGF resulted in intermolecular transphosphorylation of Flk1, thereby
      amplifying VEGF-driven angiogenesis through Flk1. Even though VEGF and PGF both
      bind Flt1, PGF uniquely stimulated the phosphorylation of specific Flt1 tyrosine
      residues and the expression of distinct downstream target genes. Furthermore, the
      VEGF/PGF heterodimer activated intramolecular VEGF receptor cross talk through
      formation of Flk1/Flt1 heterodimers. The inter- and intramolecular VEGF receptor
      cross talk is likely to have therapeutic implications, as treatment with VEGF/PGF
      heterodimer or a combination of VEGF plus PGF increased ischemic myocardial
      angiogenesis in a mouse model that was refractory to VEGF alone.

PMID- 12796774
TI  - Rapid myeloerythroid repopulation after intrafemoral transplantation of NOD-SCID
      mice reveals a new class of human stem cells.
AB  - A major problem hampering effective stem cell-based therapies is the absence of a
      clear understanding of the human hematopoietic stem cell (HSC) pool composition.
      The severe combined immunodeficiency (SCID) repopulating cell (SRC)
      xenotransplant assay system provides a powerful tool for characterizing the
      frequency, cell surface markers, cell cycle status, homing and response to
      cytokine stimulation of human HSCs. Clonal tracking of retrovirally transduced
      SRCs and transplantation of specific subpopulations revealed SRC classes with
      distinct repopulation potentials. However, all HSC repopulation assays are based
      on intravenous injection, a complex process that requires circulation through
      blood, recognition and extravasation through bone marrow vasculature, and
      migration to a supportive microenvironment. Thus, some classes of HSCs may remain
      undetected. By direct intrafemoral injection, we identified rapid SRCs (R-SRCs)
      within the Lin-CD34+CD38loCD36- subpopulation. R-SRCs rapidly generate high
      levels of human myeloid and erythroid cells within the injected femur, migrate to
      the blood and colonize individual bones of non-obese diabetic (NOD)-SCID mice
      within 2 weeks after transplantation. Lentivector-mediated clonal analysis of
      individual R-SRCs revealed heterogeneity in their proliferative and migratory
      properties. The identification of a new HSC class and an effective intrafemoral
      assay provide the tools required to develop more effective stem cell-based
      therapies that rely on rapid reconstitution.

PMID- 12796775
TI  - A structural basis for immunodominant human T cell receptor recognition.
AB  - The anti-influenza CD8+ T cell response in HLA-A2-positive adults is almost
      exclusively directed at residues 58-66 of the virus matrix protein (MP(58-66)).
      V(beta)17V(alpha)10.2 T cell receptors (TCRs) containing a conserved arginine
      serine-serine sequence in complementarity determining region 3 (CDR3) of the
      V(beta) segment dominate this response. To investigate the molecular basis of
      immunodominant selection in an outbred population, we have determined the crystal
      structure of V(beta)17V(alpha)10.2 in complex with MP(58-66)-HLA-A2 at a
      resolution of 1.4 A. We show that, whereas the TCR typically fits over an exposed
      side chain of the peptide, in this structure MP(58-66) exposes only main chain
      atoms. This distinctive orientation of V(beta)17V(alpha)10.2, which is almost
      orthogonal to the peptide-binding groove of HLA-A2, facilitates insertion of the
      conserved arginine in V(beta) CDR3 into a notch in the surface of MP(58-66)-HLA
      A2. This previously unknown binding mode underlies the immunodominant T cell
      response.

PMID- 12796776
TI  - BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.
AB  - During activation, T cells express receptors for receiving positive and negative
      costimulatory signals. Here we identify the B and T lymphocyte attenuator (BTLA),
      an immunoglobulin domain-containing glycoprotein with two immunoreceptor tyrosine
      based inhibitory motifs. BTLA is not expressed by naive T cells, but it is
      induced during activation and remains expressed on T helper type 1 (T(H)1) but
      not T(H)2 cells. Crosslinking BTLA with antigen receptors induces its tyrosine
      phosphorylation and association with the Src homology domain 2 (SH2)-containing
      protein tyrosine phosphatases SHP-1 and SHP-2, and attenuates production of
      interleukin 2 (IL-2). BTLA-deficient T cells show increased proliferation, and
      BTLA-deficient mice have increased specific antibody responses and enhanced
      sensitivity to experimental autoimmune encephalomyelitis. B7x, a peripheral
      homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on
      T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4
      (CTLA-4) and programmed death 1 (PD-1).

PMID- 12796777
TI  - An essential role for NOD1 in host recognition of bacterial peptidoglycan
      containing diaminopimelic acid.
AB  - Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family
      that includes multiple members with NOD and leucine-rich repeats in vertebrates
      and plants. NOD1 has been suggested to have a role in innate immune responses,
      but the mechanism involved remains unknown. Here we report that NOD1 mediates the
      recognition of peptidoglycan derived primarily from Gram-negative bacteria.
      Biochemical and functional analyses using highly purified and synthetic compounds
      indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D
      glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1
      did not secrete cytokines in response to synthetic iE-DAP and did not prime the
      lipopolysaccharide response. Thus, NOD1 mediates selective recognition of
      bacteria through detection of iE-DAP-containing peptidoglycan.

PMID- 12796779
TI  - Imprinted microRNA genes transcribed antisense to a reciprocally imprinted
      retrotransposon-like gene.
AB  - MicroRNAs (miRNAs) are an abundant class of RNAs that are approximately 21-25
      nucleotides (nt) long, interact with mRNAs and trigger either translation
      repression or RNA cleavage (RNA interference, RNAi) depending on the degree of
      complementarity with their targets. Here we show that the imprinted mouse distal
      chromosome 12 locus encodes two miRNA genes expressed from the maternally
      inherited chromosome and antisense to a retrotransposon-like gene (Rtl1)
      expressed only from the paternal allele.

PMID- 12796778
TI  - 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a
      molecular explanation for Miller-Dieker syndrome.
AB  - Heterozygous deletions of 17p13.3 result in the human neuronal migration
      disorders isolated lissencephaly sequence (ILS) and the more severe Miller-Dieker
      syndrome (MDS). Mutations in PAFAH1B1 (the gene encoding LIS1) are responsible
      for ILS and contribute to MDS, but the genetic causes of the greater severity of
      MDS are unknown. Here, we show that the gene encoding 14-3-3epsilon (YWHAE), one
      of a family of ubiquitous phosphoserine/threonine-binding proteins, is always
      deleted in individuals with MDS. Mice deficient in Ywhae have defects in brain
      development and neuronal migration, similar to defects observed in mice
      heterozygous with respect to Pafah1b1. Mice heterozygous with respect to both
      genes have more severe migration defects than single heterozygotes. 14-3-3epsilon
      binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL
      phosphorylation. Similar to LIS1, deficiency of 14-3-3epsilon results in
      mislocalization of NUDEL and LIS1, consistent with reduction of cytoplasmic
      dynein function. These results establish a crucial role for 14-3-3epsilon in
      neuronal development by sustaining the effects of CDK5 phosphorylation and
      provide a molecular explanation for the differences in severity of human neuronal
      migration defects with 17p13.3 deletions.

PMID- 12796781
TI  - Induction of an interferon response by RNAi vectors in mammalian cells.
AB  - DNA vectors that express short hairpin RNAs (shRNAs) from RNA polymerase III (Pol
      III) promoters are a promising new tool to reduce gene expression in mammalian
      cells. shRNAs are processed to small interfering RNAs (siRNAs) of 21 nucleotides
      (nt) that guide the cleavage of the cognate mRNA by the RNA-induced silencing
      complex. Although siRNAs are thought to be too short to induce interferon
      expression, we report here that a substantial number of shRNA vectors can trigger
      an interferon response.

PMID- 12796780
TI  - Cadmium is a mutagen that acts by inhibiting mismatch repair.
AB  - Most errors that arise during DNA replication can be corrected by DNA polymerase
      proofreading or by post-replication mismatch repair (MMR). Inactivation of both
      mutation-avoidance systems results in extremely high mutability that can lead to
      error catastrophe. High mutability and the likelihood of cancer can be caused by
      mutations and epigenetic changes that reduce MMR. Hypermutability can also be
      caused by external factors that directly inhibit MMR. Identifying such factors
      has important implications for understanding the role of the environment in
      genome stability. We found that chronic exposure of yeast to environmentally
      relevant concentrations of cadmium, a known human carcinogen, can result in
      extreme hypermutability. The mutation specificity along with responses in
      proofreading-deficient and MMR-deficient mutants indicate that cadmium reduces
      the capacity for MMR of small misalignments and base-base mismatches. In extracts
      of human cells, cadmium inhibited at least one step leading to mismatch removal.
      Together, our data show that a high level of genetic instability can result from
      environmental impediment of a mutation-avoidance system.

PMID- 12796782
TI  - Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations
      during sleep.
AB  - In rodents, the electroencephalogram (EEG) during paradoxical sleep and
      exploratory behavior is characterized by theta oscillations. Here we show that a
      deficiency in short-chain acyl-coenzyme A dehydrogenase (encoded by Acads) in
      mice causes a marked slowing in theta frequency during paradoxical sleep only. We
      found Acads expression in brain regions involved in theta generation, notably the
      hippocampus. Microarray analysis of gene expression in mice with mutations in
      Acads indicates overexpression of Glo1 (encoding glyoxylase 1), a gene involved
      in the detoxification of metabolic by-products. Administration of acetyl-L
      carnitine (ALCAR) to mutant mice significantly recovers slow theta and Glo1
      overexpression. Thus, an underappreciated metabolic pathway involving fatty acid
      beta-oxidation also regulates theta oscillations during sleep.

PMID- 12796783
TI  - Postsynaptic requirement for Abl kinases in assembly of the neuromuscular
      junction.
AB  - Agrin signals through the muscle-specific receptor tyrosine kinase (MuSK) to
      cluster acetylcholine receptors (AChRs) on the postsynaptic membrane of the
      neuromuscular junction (NMJ). This stands as the prevailing model of synapse
      induction by a presynaptic factor, yet the agrin-dependent MuSK signaling cascade
      is largely undefined. Abl1 (previously known as Abl) and the Abl1-related gene
      product Abl2 (previously known as Arg) define a family of tyrosine kinases that
      regulate actin structure and presynaptic axon guidance. Here we show that the Abl
      kinases are critical mediators of postsynaptic assembly downstream of agrin and
      MuSK. In mouse muscle, Abl kinases were localized to the postsynaptic membrane of
      the developing NMJ. In cultured myotubes, Abl kinase activity was required for
      agrin-induced AChR clustering and enhancement of MuSK tyrosine phosphorylation.
      Moreover, MuSK and Abl kinases effected reciprocal tyrosine phosphorylation and
      formed a complex after agrin engagement. Our findings suggest that Abl kinases
      provide the developing synapse with the kinase activity required for signal
      amplification and the intrinsic cytoskeletal regulatory capacity required for
      assembly and remodeling.

PMID- 12796786
TI  - High incidence of graft failure in children receiving CD34+ augmented elutriated
      allografts for nonmalignant diseases.
AB  - T-cell depletion of the marrow graft using counterflow centrifugal elutriation
      reduces the risk of graft-versus-host disease (GVHD). However, because of high
      rates of graft failure and relapse, elutriation alone has not improved survival.
      We have carried out a phase II clinical trial in 54 pediatric patients to
      determine if CD34+ selection to rescue pluripotent stem cells from the small
      lymphocyte fraction improves engraftment. The processed grafts contained a mean
      of 5.5 x 10(7) cells/kg IBW, 4.7 x 10(6) CD34+ cells/kg IBW, and 6.3 x 10(5)
      CD3+cells/kg IBW. Patients achieved an ANC >500 at a median of 16 days and
      platelet count >20 000 at a median of 28 days. The incidence of clinically
      significant GVHD was 19%. In total, 10 patients enrolled in this study
      experienced graft failure, with eight of the 14 patients transplanted for
      nonmalignant indications failing to engraft stably. Graft failure was
      statistically significantly associated with nonmalignant diagnosis (P<0.001), but
      was not associated with CMV seropositivity, donor gender, or cell counts of the
      allograft. We conclude that although time to engraftment is similar to that seen
      with unmanipulated grafts, graft failure remains a significant problem in
      patients with hereditary, nonmalignant diseases. Future efforts will seek to
      preserve the benefits of elutriation with CD34+ selection by increasing immune
      ablation of the preparative regimen and/or increasing posttransplant immune
      suppression.

PMID- 12796784
TI  - Brain-derived neurotrophic factor regulates energy balance downstream of
      melanocortin-4 receptor.
AB  - The melanocortin-4 receptor (MC4R) is critically involved in regulating energy
      balance, and obesity has been observed in mice with mutations in the gene for
      brain-derived neurotrophic factor (BDNF). Here we report that BDNF is expressed
      at high levels in the ventromedial hypothalamus (VMH) where its expression is
      regulated by nutritional state and by MC4R signaling. In addition, similar to
      MC4R mutants, mouse mutants that expresses the BDNF receptor TrkB at a quarter of
      the normal amount showed hyperphagia and excessive weight gain on higher-fat
      diets. Furthermore, BDNF infusion into the brain suppressed the hyperphagia and
      excessive weight gain observed on higher-fat diets in mice with deficient MC4R
      signaling. These results show that MC4R signaling controls BDNF expression in the
      VMH and support the hypothesis that BDNF is an important effector through which
      MC4R signaling controls energy balance.

PMID- 12796785
TI  - Neurexin mediates the assembly of presynaptic terminals.
AB  - Neurexins are a large family of proteins that act as neuronal cell-surface
      receptors. The function and localization of the various neurexins, however, have
      not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1,
      a postsynaptic membrane protein that can trigger synapse formation at axon
      contacts. Here we report that neurexins are concentrated at synapses and that
      purified neuroligin is sufficient to cluster neurexin and to induce presynaptic
      differentiation. Oligomerization of neuroligin is required for its function, and
      we find that beta-neurexin clustering is sufficient to trigger the recruitment of
      synaptic vesicles through interactions that require the cytoplasmic domain of
      neurexin. We propose a two-step model in which postsynaptic neuroligin multimers
      initially cluster axonal neurexins. In response to this clustering, neurexins
      nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus
      is recruited.

PMID- 12796787
TI  - Paediatric allogeneic bone marrow transplantation for homozygous beta
      thalassaemia, the Dutch experience.
AB  - We reviewed the results of the Dutch paediatric bone marrow transplant (BMT)
      program for children receiving HLA-identical BMT for beta-thalassaemia major over
      an 18-year period. In all, 19 patients underwent a total of 21 transplants in our
      treatment centre between July 1984 and February 2002. Eight females (age 0.3-12
      years; median 5 years) and 11 males (age 0.8-18 years; median 6 years) were
      included. Information, prospectively collected, included molecular defects, donor
      genotype, beta/alpha-globin expression rates, serum ferritin levels, hepato
      splenomegaly, chelation history, virology screening, liver pathology together
      with post-transplant outcome inclusive of leucocyte chimerism. In total, 11
      patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with
      or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring
      in six patients. Of these, two children underwent a second successful SCT. For
      this group, overall event-free survival (EFS) and disease-free survival (DFS)
      were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was
      55%. Subsequent addition of melphalan to the conditioning regimen resulted in
      long-term stable engraftment in all patients with an EFS/DFS for this group of
      90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at
      5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21
      transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT beta/alpha
      synthetic ratio measurement monitored donor erythroid engraftment and predicted
      rejection with a return to transfusion dependency. Maintained full donor
      chimerism is indicative of stable engraftment both for leucocyte and erythroid
      lineages, whereas mixed donor chimerism is not. Our results emphasise the
      importance of the conditioning regimen and post-transplant chimerism surveillance
      predictive of rejection or long-term stable engraftment.

PMID- 12796788
TI  - Reduced intensity conditioning for allogeneic hematopoietic stem cell
      transplantation in patients with acute myeloid leukemia: disease status by marrow
      blasts is the strongest prognostic factor.
AB  - We analyzed predictive factors for the outcome of 113 acute myeloid leukemia
      patients receiving reduced-intensity conditioning prior to allogeneic
      hematopoietic stem cell transplantation (HSCT). Patients were ineligible for
      conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the
      conventional dose of busulfan (n=93) or total body irradiation (n=20). The source
      of stem cells was blood in 102 patients, marrow in 10, and both in one. In total,
      50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched
      and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In
      all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a
      median time of 13.5 and 13 days. The probabilities of event-free survival (EFS)
      (median follow-up: 12 months) were 49% for patients with less than 5% blasts in
      the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts
      (P<or=0.001). Death occurred because of relapse in 29 patients (25.6%), infection
      in 12 patients (10.6%), acute graft-versus-host disease in eight patients (7.0%)
      and organ toxicity in nine patients (7.9%). In multivariate analysis, higher
      number of blasts in the marrow, alternative donors and low Karnofsky performance
      score were independent adverse prognostic factors for EFS.

PMID- 12796789
TI  - Hematopoietic stem cell transplantation in patients with severe Langerhans cell
      histiocytosis and hematological dysfunction: experience of the French Langerhans
      Cell Study Group.
AB  - The aim of this study was to assess the results of hematopoietic stem cell
      transplantation (HSCT) in refractory Langerhans cell histiocytosis (LCH). Among
      85 patients with LCH and hematological dysfunction diagnosed in France between
      1987 and 2000, eight received HSCT in six institutions. Median age at diagnosis
      was 0.54 years. The median LCH activity score at diagnosis was 10 (range 3-20).
      All patients responded poorly to initial chemotherapy. At the time of HSCT, the
      median activity score was 16.5 (range 7-18). HSCT was autologous in three cases
      and allogeneic in five cases. The conditioning regimen consisted of TBI in two
      cases and chemotherapy alone in six cases. Conditioning had to be attenuated in
      two patients. All patients had persistent active disease after autologous HSCT,
      which was fatal in two cases and controlled by chemotherapy in one case. After
      allogeneic HSCT, two patients died from toxicity and three had complete
      responses; two patients had had no recurrences after 21 months and 7 years of
      follow-up, while the other patient relapsed and died from sepsis related to
      splenectomy. HSCT for refractory LCH can thus be highly toxic but can also
      achieve sustained disease control.

PMID- 12796790
TI  - Outcome of 27 patients with Hurler's syndrome transplanted from either related or
      unrelated haematopoietic stem cell sources.
AB  - Over the last 15 years, we have performed a total of 30 haematopoietic stem cell
      transplants on 27 children suffering from Hurler's syndrome. These children were
      of median age 11 months at the time of diagnosis and 25 months at the time of
      transplantation. The phenotype was severe in 21 cases (78%). The donor was
      familial in 13 cases: nine genotypically identical, one phenotypically identical
      father and three HLA-mismatched donors. Unrelated donors were selected in 17
      cases: four phenotypically identical and 13 with 1-4 HLA mismatches. The
      conditioning regimen generally consisted of busulphan 600 mg/m(2) plus
      cyclophosphamide (Endoxan) 260 mg/kg and cyclosporin with methotrexate for GvHD
      prophylaxis. Rabbit anti-thymocyte globulin (Thymoglobuline) was given for all
      unrelated or familial mismatched transplantations. The median nucleated cell dose
      infused was 6.00 x 10(8) TNC/kg. No bone marrow (apart from one) was T cell
      depleted. For first transplants, engraftment was observed in 23/27 patients (pts)
      (85%). Primary graft failure was observed in 4/27 patients (16%), two were
      retransplanted from an unrelated donor, one with success. Four patients have
      died. The primary cause of death was infection in three cases (TRM : 11%) and
      disease progression in one case, after primary graft failure. Of the 23 living
      patients, two have disease progression after graft failure and 21 (78%) have
      functional grafts with a favourable long-term outcome after a median follow-up of
      4.7 years, having either full or mixed chimaerism. Among surviving patients with
      functional grafts, 13 (62%) were transplanted from unrelated donors of whom 10
      (77 %) had HLA disparities. There was a remarkably low incidence of GvHD. In our
      experience, haematopoietic stem cell transplantation using an HLA-matched
      familial donor or an HLA-matched or -mismatched unrelated donor without T cell
      depletion or irradiation can achieve a favourable outcome in Hurler's syndrome,
      with improved cognitive function, but with a limited effect on the corneas and
      skeleton.

PMID- 12796791
TI  - Ex vivo purging with NK-92 prior to autografting for chronic myelogenous
      leukemia.
AB  - Although controversial, purging of the autograft may be necessary to optimize
      transplant outcome, especially if better treatments become available to eliminate
      or control residual disease that may be left after the conditioning regimen. The
      intent of this study was to show that immunological purging with the cytotoxic
      cell line NK-92 effectively reduces the number of clonogenic cells and that the
      method can be performed in compliance with GMP. Owing to the easy quantification
      of bcr-abl transcripts, chronic myelogenous leukemia (CML) was used as a model
      disease for proof of principle. A detection level of 10(-7) bcr-abl+ cells and
      purging efficiency of four logs were achievable for the bcr-abl+ cell line, K562.
      Leukapheresis products collected from CML patients after stem cell mobilization
      were then tested. For all patients tested, residual CML cells were highly
      sensitive to purging by NK-92 with a purging efficacy of several logs. No adverse
      effect on hematopoietic progenitor cell function was noted. These results
      demonstrate the efficacy of NK-92 as a purging agent to decrease or eliminate
      malignant contamination of autologous stem cell grafts and establish proof of
      principle for ex vivo purging of CML autografts using cytotoxic effector cells.

PMID- 12796792
TI  - Lack of clinical utility of minimal residual disease detection in allogeneic stem
      cell recipients with childhood acute lymphoblastic leukemia: multi-institutional
      collaborative study in Japan.
AB  - The clinical utility of minimal residual disease (MRD) measurements following
      allogeneic stem cell transplantation (SCT) in childhood ALL is controversial. We
      therefore performed a multi-institutional study of MRD in bone marrow samples
      taken before SCT and at 1, 3, 6 and 12 months after SCT. Case-specific clonal
      rearrangements of IgH and TCR genes and expression levels of Wilms' tumor 1 (WT1)
      mRNA were determined by PCR or RT-PCR methods. In total, 95 cases met all
      criteria for analysis of informative IgH/TCR markers and quantitative WT1 mRNA
      expression levels. During the 2-year (median 414 days) study period, 20 patients
      relapsed. Although the proportion of patients with a positive IgH/TCR result
      before SCT was significantly reduced at 1 month after treatment (P<0.001),
      attesting the efficacy of SCT, serial measurements of IgH/TCR rearrangements did
      not correlate with leukemic relapse. Clonal switch was demonstrated in 11 of the
      14 patients with bone marrow relapse, indicating that the poor predictive power
      of the MRD assay most likely reflected the loss of PCR targets. WT1 expression
      was not related to either MRD detection by IgH/TCR assays or to clinical leukemic
      relapse. The clinical value of serial MRD monitoring would be limited in ALL
      patients undergoing SCT.

PMID- 12796793
TI  - Procalcitonin, C-reactive protein, and endotoxin after bone marrow
      transplantation: identification of children at high risk of morbidity and
      mortality from sepsis.
AB  - We prospectively evaluated the capacity of serum procalcitonin (PCT), compared
      with serum levels of C-reactive protein (CRP) and endotoxin, to identify children
      at high risk for mortality from sepsis after BMT. Of 47 pediatric bone marrow
      transplantation patients studied, 22 had an uneventful course post-transplant
      (Group 1), 17 survived at least one septic event (Group 2), and eight died from
      multiorgan failure (MOF) following septic shock (Group 3). Median concentrations
      of PCT over the course of the study were 1.3, 15.2, and 102.8 ng/ml,
      respectively, in each of the three groups (P<0.002 for each comparison). Median
      concentrations of CRP were 91, 213, and 260 mg/l, respectively (P<0.001 for Group
      1 vs Group 2 and Group 3; P=NS for Group 2 vs Group 3). Median concentrations of
      endotoxin were 0.21, 0.30, and 0.93 U/l, respectively (P=NS for each comparison).
      Median concentrations of PCT, in contrast to serum CRP and endotoxin, correlated
      with the severity of sepsis (8.2 ng/ml in 'sepsis' and 22.3 ng/ml in 'severe
      sepsis', P=0.028) and provided useful prognostic information during septic
      episodes.

PMID- 12796794
TI  - Low molecular weight heparin for the prevention of hepatic veno-occlusive disease
      (VOD) after hematopoietic stem cell transplantation: a prospective phase II
      study.
AB  - We evaluated 40 patients undergoing high-dose chemo/radiotherapy (HDCT) and
      hematopoietic stem cell transplantation (HSCT) (allogeneic (22), autologous (18))
      to determine the safety and feasibility of administering low molecular weight
      heparin (LMWH) as hepatic veno-occlusive disease (VOD) prophylaxis. Patients
      received a once daily subcutaneous injection of dalteparin 2500 anti-Xa i.u.
      commencing the day prior to starting HDCT, and continuing until day +30 post HSCT
      or hospital discharge, whichever came first. Dosage adjustments were made for
      patients developing renal failure. All bleeding episodes were recorded and graded
      and VOD was diagnosed and graded according to Seattle criteria. At 100 days of
      follow-up, the overall survival and probability of regimen-related mortality were
      85 and 15%, respectively. Nine patients developed VOD. The probability of
      developing VOD post allogeneic and autologous HSCT was 28% (95% CI, 6-45) and 17%
      (95% CI, 0-32), respectively. VOD was graded as moderate (n=8) and severe (n=1).
      VOD resolved in all cases except for one patient who died secondary to severe VOD
      and multiorgan failure. Clinically significant bleeding episodes occurred in
      three patients; 24 patients developed minor bleeding not requiring specific
      therapy. All bleeding episodes resolved. These results suggest that LMWH for VOD
      prophylaxis is safe with a low incidence of serious bleeding events. Whether it
      is superior to unfractionated heparin, however, is unknown and should be
      addressed within the context of a randomized controlled trial.

PMID- 12796795
TI  - Eye shielding during total body irradiation for bone marrow transplantation in
      children transplanted for a hematological disorder: risks and benefits.
AB  - This is a retrospective analysis of 188 children who underwent total body
      irradiation (TBI) in one or two fractions before bone marrow transplantation
      (BMT) for a hematological disorder. While 139 children had eye shielding during
      TBI to decrease cataract formation, 49 did not. The blocks used for shielding
      caused cylindrical areas of decreased dose intensity in the brain. The aim of the
      study was to determine if there was an increased risk of relapse in the eyes or
      in the CNS after shielding of the eyes. The probability and severity of cataract
      formation with and without shielding were also evaluated. None of the 49 children
      without shielding had a relapse in their eyes or in the CNS after BMT. Of the
      children with shielding, none had a relapse in the eyes but two of the 139 (1.4%)
      had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21
      evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts
      were present in eight of 21 (38%) patients without and two of 64 (3%) patients
      with shielding. The probability of staying cataract free for at least five years
      was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24
      respectively. The relative risk of developing a cataract without shielding vs
      shielding was three (95% CI=1.5; 5.9). It appears that the incidence of relapse
      in the eyes and CNS is not increased when the eyes are shielded during TBI.
      Shielding increased the latency time of cataract formation and decreased the
      severity of cataracts.

PMID- 12796796
TI  - Idiopathic pneumonia syndrome after high-dose chemotherapy and autologous
      hematopoietic stem cell transplantation for high-risk breast cancer.
AB  - Our aim was to describe the incidence, clinical course, and risk factors for
      idiopathic pneumonia syndrome (IPS) after high-dose chemotherapy with
      cyclophosphamide, carmustine, and thiotepa followed by autologous stem cell
      transplantation for high-risk breast cancer. Charts for patients who underwent
      high-dose chemotherapy for high-risk breast cancer at a single center from 1992
      to 2000 were retrospectively reviewed, and potential risk factors for development
      of IPS were sought with the log-rank test. Of 164 patients reviewed, 20 developed
      IPS at a median onset of 87 days after the transplant (range, 2-257 days). The
      actuarial incidence of IPS in the first 100 days after the transplant was 8%, and
      95% of patients developed symptoms within the first 6 months after transplant.
      Patient age, smoking status, breast cancer stage at diagnosis, and pretransplant
      lung function did not predict development of IPS. Three patients died of
      progressive pulmonary failure and the IPS resolved in the other 17. We concluded
      that IPS is an important cause of morbidity and mortality in patients with high
      risk breast cancer undergoing high-dose chemotherapy. Given the absence of
      predictive factors, any pulmonary symptoms appearing in the first year after the
      transplant should be evaluated carefully.

PMID- 12796797
TI  - Successful treatment of bcr/abl-positive acute mixed lineage leukemia by
      unmanipulated bone marrow transplantation from an HLA-haploidentical (3-antigen
      mismatched) cousin.
AB  - We describe a patient with bcr/abl-positive acute mixed lineage leukemia who
      successfully underwent transplantation in primary induction failure, using
      unmanipulated bone marrow from a human leukocyte antigen (HLA)-haploidentical
      cousin. The tumor burden was successfully reduced by the administration of
      imatinib mesylate (STI571) before transplantation. As graft-versus-host disease
      (GVHD) prophylaxis, a combination of tacrolimus and a short course of
      methotrexate, methylprednisolone, and mycophenolate mofetil was used.
      Hematopoietic reconstitution was rapid, and acute GVHD was limited to the skin
      (grade I). The patient is still in complete remission past day +400. This
      successful case suggests that HLA-haploidentical transplantation using
      unmanipulated marrow from a distantly related relative can be considered for
      patients in urgent situations who do not have HLA-identical donors.

PMID- 12796798
TI  - Successful treatment of natural killer (NK) cell leukemia following a long
      standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone
      marrow transplantation.
AB  - The optimal treatment for natural killer (NK) cell leukemia after chronic active
      Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy
      presented with NK cell leukemia following CAEBV infection for 5 years. The
      peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular
      lymphocytes and a monoclonal integration of the EBV genome was detected.
      Chemotherapy was not sufficiently effective to control the disease. Allogeneic
      BMT from an HLA-identical sister was performed using a conditioning regimen
      consisting of total body irradiation, cyclophosphamide and thiotepa. The patient
      is disease-free with a perfect performance status 24 months after BMT. This is
      the first report to show that allogeneic BMT is potentially able to cure NK cell
      leukemia after CAEBV infection.

PMID- 12796800
TI  - T-cell depletion does not necessarily compromise donor stem cell engraftment in
      patients receiving reduced-intensity conditioning regimens.

PMID- 12796799
TI  - Acute renal failure due to adenovirus-associated obstructive uropathy and
      necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient.
AB  - Management of post-transplant complications caused by severe adenoviral infection
      remains a major therapeutic challenge. A 17-year-old male who had undergone bone
      marrow transplantation for the treatment of acute lymphoblastic leukemia
      developed complete anuria following hemorrhagic cystitis 34 days after the
      transplant procedure. The computed tomogram scan revealed bilateral
      hydronephrosis, indicating acute renal failure because of obstructive uropathy.
      The emergency procedure of percutaneous nephrostomy caused massive bleeding in
      the left kidney, which eventually required a nephrectomy. Adenovirus-positive
      severe necrotizing tubulointerstitial nephritis was the histopathological
      diagnosis. Post-transplant acute renal failure because of hydronephrosis, which
      could be complicated by adenovirus-induced renal parenchymal disease, is of great
      concern and may cause significant problems with interventional treatment.

PMID- 12796802
TI  - Bacteremic cellulitis caused by non-O1, non-O139 Vibrio cholerae in a patient
      following hematopoietic stem cell transplantation.

PMID- 12796803
TI  - Use of recombinant factor VIIa in life-threatening bleeding following autologous
      peripheral blood stem cell transplantation complicated by platelet
      refractoriness.

PMID- 12796807
TI  - Atomic force microscopy of actin.
AB  - Atomic force microscope (AFM) is a powerful and novel tool to investigate the
      surface and submembranous structures of living cells under physiological
      conditions at high resolution, and has force measure at nano-Newton level. AFM
      can image and manipulate samples (single macromolecule, cells, and so on) at very
      high, sometimes atomic resolution by scanning a fine tip over the surface of
      interest and detecting physical interactions between the tip and sample. Actin is
      one of the most important proteins, involved extensively in various cell
      physiological activities and functions in eukaryotes. The present paper clarified
      the crucial significance and the enormous applicable prospects of AFM in modern
      biological sciences by reviewing the usage of AFM in actin study, which can be
      taken as a good example for expounding almost all functions that AFM owns, and
      can be utilized in life sciences exploration.

PMID- 12796808
TI  - [The biological characteristics of SARS virus and its related coronaviruses].
AB  - Cases of the life-threatening respiratory disease with no identified cause
      (designated as "severe acute respiratory syndrome", SARS, in March 2003) were
      first reported in late 2002 from Guangdong Province, China; they were followed by
      reports from about other 30 countries (or regions) such as Vietnam, Singapore,
      Thailand, Hong Kong (China), Canada, and USA etc. Because of its ongoing epidemic
      and high death rate, SARS has shined an intense spotlight all over the world. The
      World Health Organization (WHO) has promptly established a network of
      international laboratories consisting of 13 members around the 10 countries to
      facilitate the identification of the causative agent of SARS. A novel
      coronavirus, SARS virus, fulfilling all of Koch's postulates was announced to be
      the primary aetiological agent of SARS on April 16 by WHO shortly after the
      Canadian scientists released the full-length genome sequence of SARS virus (Tor2)
      on April 12. China is now facing a formidable task to fight SARS. In this
      article, we present a brief summary on the biological characteristics of
      coronavirus with its associated diseases, and make some suggestions on how to
      curb this outbreak and how to cure SARS disease based on the potential targets of
      this novel virus.

PMID- 12796810
TI  - The effects of inhibiting P18(INK4C) expression on the invasion of gastric
      adenocarcinoma cell line.
AB  - Using cDNA microarray with double dots of 4096 human genes, P18(INK4C), a member
      of CKI, was found down-regulated in a gastric adenocarcinoma metastatic cell line
      (RF-48), compared with the corresponding primary cancer cell line (RF-1), which
      implied that P18(INK4C) might be involved in cell invasion and metastatic
      progression of human gastric adenocarcinoma. Antisense RNA expression plasmid was
      applied to inhibit P18(INK4C) expression to study the effect of decreased
      P18(INK4C) expression on cell migration, invasion and proliferation ability and
      cell cycle of RF-1. Results showed that inhibition of P18(INK4C) expression could
      obviously enhance cell invasion ability of RF-1, but had little effect on its
      cell cycle and cell migration and proliferation ability. These results implied
      that P18(INK4C) might play a pivotal role in regulating cell invasion, rather
      than regulating cell cycle and proliferation in the progression of human gastric
      adenocarcinoma as expected before.

PMID- 12796809
TI  - A new model of trispecific antibody resulting the cytotoxicity directed against
      tumor cells.
AB  - Bispecific antibodies (BsAb) with specificity to both tumor cells and CD3
      molecule were believed to be promising immunological tools for the therapy with
      minimal residual diseases by activating cytotoxic T cells. However, without
      costimulatory molecule CD28, the activated T cells tended to apoptosis. In order
      to kill tumor cells more efficiently, a recombinant multifunctional single-chain
      trispecific antibody (scTsAb), which contains anti-ovarian carcinoma (OC) scFv,
      anti-CD3 scFv and VH domain of anti-CD28 antibody, was constructed and expressed
      in E. coli BL21 Star strain. The scTsAb showed strong binding avidities to
      membrane antigen of SK-OV-3 cell, CD3 molecule on Jurkat cell, and recombinant
      CD28 antigen. It was further demonstrated that this scTsAb could activate
      peripheral blood T cells to elicit strong cytotoxicity against SK-OV-3 cells.
      This new type of recombinant scFv antibody set up a new technological platform
      for T cells based immunotherapy against cancer, especially with the failure on
      MHC antigen presentation or absence of costimulating signal.

PMID- 12796811
TI  - The phosphorylation of NS protein of wheat rosette stunt virus.
AB  - The genome of wheat rosette stunt virus (WRSV), a plant rhabdovirus, is a single
      negative strand RNA. It encodes five viral structural proteins: the glycoprotein
      (G), the matrix protein (M), the nucleocapsid protein (N), the large protein (L)
      and the non?structural protein (NS), which was later proved to be a viral
      structural protein too and existed in a variety of phosphorylation forms in case
      of vascular stomatitis virus (VSV). In this paper we demonstrated that NS protein
      of WRSV, either bound with the viral nucleocapsid or expressed in bacteria could
      be in vitro phosphorylated in presence of viral nucleocapsid. We concluded that
      the NS protein of WRSV was a phosphorylated protein and it might exist in both
      phosphorylated and dephosphorylated forms in virions. Our results excluded the
      possibility that the NS protein could be autophosphorylated. The L protein, the
      major component of viral RNA dependent RNA polymerase is associated with the
      protein kinase for phosphorylation of NS protein.

PMID- 12796812
TI  - Differential protein expression induced by transient transfection of
      metallothionein-3 gene in SH-SY5Y neuroblastoma cell line.
AB  - Metallothionein-3(MT-3), also known as growth inhibitory factor (GIF), is
      predominantly expressed in central nervous system (CNS). It belongs to the family
      of metallothionein(MT) but has several unique properties that are not shared by
      other family members such as MT-1/MT-2. In the past few years, MT-3 had been
      postulated to be a multipurpose protein which could play important
      neuromodulatory and neuroprotective roles in CNS besides the common roles of MTs.
      However, the primary function of MT-3 and the mechanism underlying its multiple
      functions were not elucidated so far. In present study, human neuroblastoma cell
      line SH-SY5Y was employed to study the overall cellular protein changes induced
      by transient transfection of MT-3 gene, based on comparative proteome analysis.
      Averagely about 750 spots were visualized by Coomassie staining in one 2D gel, in
      which 17 proteins were shown to display significant and reproducible changes by
      semiquantitative analysis with ImageMaster 2D Elite software. Among them, 12
      proteins were up-regulated while other 5 proteins were down-regulated. Using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 10
      proteins were further identified to be zinc finger protein, glutamate
      transporter, and enhancer protein, etc., which were involved in several important
      pathways regulating the functions of central nervous system. The results showed
      that MT-3 might exert its unique functions by regulating the expression of these
      proteins.

PMID- 12796813
TI  - [Establishment of a SCID mouse model for synergistic anti-tumor effect of human
      IL-12 and B7-1].
AB  - Human IL-12(hIL-12) has weak effect on mouse immunity cells, so the practical
      animal model is not available for the study of hIL-12 anti-tumor activity. In
      this work, the improved Winn assay was applied to evaluate the synergistic anti
      tumor effects of hIL-12 and human costimulatory molecule B7-1(hB7-1) on human
      tumor in HuPBL-SCID mouse model. Three gene transferring solutions hIL-12, hB7-1
      and their mixture(1:1) were prepared using the nonliposome transgene reagent and
      the expressing vectors, and hIL-12, hB7-1 or their mixture were transferred into
      tumor cell A375 respectively. Then A375 were co-injected into SCID mice with
      HuPBL, and rhIL-2 were injected i.p. as an anti-tumor agitator. On the other
      hand, LoVo and SPC tumor cells were also used to test the inhibitory effect of
      the mixture of hIL-12 and hB7-1. The anti-tumor effect of transferred genes was
      estimated by detecting tumor inhibition rate. Furthermore, the histochemical
      change of A375 implanting tumor tissue was also observed. Results showed that, to
      A375, the tumor inhibition rate of hIL-12, hB7-1, or their mixture were 74.06%,
      66.98%, and 93.40%, respectively (P<0.01); and the mixture showed a good
      synergistic effect according to the Webb s fraction multiplication law. The tumor
      inhibition rate of the mixture in LoVo and SPC implanted mice were 98.37% and
      97.39% respectively, also showing a good synergistic effect. Histochemical study
      in A375 implanted mice showed that in gene transfected mice, tumor cells were
      greatly inhibited and fully intruded by HuPBL cells; while in control group,
      tumor cells grew very well and HuPBL showed a conglomeration. At last, the human
      IgG and T cells in PBL of HuPBL-SCID mice were higher than non-HuPBL-SCID mice
      implanted A375; which showed that HuPBL-SCID mice could be applied for the
      evaluation of the anti-tumor effect of human IL-12 and B7-1. All data indicated
      that the combination of hIL-12 and hB7-1 gene might be a promising approach for
      in vivo cancer therapy.

PMID- 12796814
TI  - [Identification of bone marrow stromal cells and expression of tyrosine
      hydroxylase gene in them].
AB  - The study is to establish the method of isolation and identification of bone
      marrow stromal cells and to investigate the ability of bone marrow stromal cells
      to accept and express TH gene. Cells were isolated by a density gradient
      (lymphocytes separation) and identified by BrdU labeling and fluorescence
      activated cell sorting (FACS) technology using CD11b, CD45 and CD90 antibodies.
      TH and lacZ gene were transfected to rBMSCs with an adeno-associated virus
      vector. The results showed that most tightly adherent cells in the primary
      culture were fibroblast-like and formed foci of two to four cells. The cells in
      the foci remained dormant for 2 to 4 days and then began to multiply rapidly.
      After several passages, the adherent cells became more uniformly spindle-shaped
      in appearance. BrdU, indicating that BMSCs replicate actively, labeled about
      74.9% of cultured cells. Data from FACS showed that about 75% of isolated cells
      were CD90(+)/CD45(-)/CD11b(-), which is the marker of bone marrow stromal cells.
      The efficiency of TH gene transfection was about 75%. BMSCs could readily be
      genetically engineered and could be useful delivery targets of gene therapy for
      Parkinson's disease.

PMID- 12796815
TI  - [Redox-dependent changes in structure and function of hHSF1].
AB  - To evaluate the effects of cysteine-SH-directed regents on the redox status,
      structure and function of human heat shock transcription factor 1 (hHSF1),
      treatment in vitro of hHSF1 with 0.3 0.5 mmol/L oxidizing reagent diamide (DM)
      and treatment in vivo of HeLa cells with 1 mmol/L buthionine sulfoximine (BSO),
      an inhibitor of gamma-glutamylcysteine synthetase, promoted the formation of a
      compact, intramolecularly disulfide-crosslinked, stable monomeric form of ox
      hHSF1, and blocked the trimerization and activation of HSF1. The effects of
      diamine were dose-dependent and readily could be completely reversed by adding
      0.4 0.5 mmol/L reducing reagent dithiothreitol (DTT) to the samples prior to gel
      electrophoresis. Computer modeling of the alpha-helical coiled-coil domains of
      the HSF1 monomer and trimer showed that the alignment of the N- and C-terminal
      hydrophobic repeats of HSF1 monomer could bring C(3)(Cys(153))close to C(4) and
      C(5)(Cys(373) and Cys(378), respectively), in positions permissible for disulfide
      bond formation under appropriate experimental conditions. The results suggest
      that redox-dependent thiol-disulfide exchange can provide a mechanism for
      regulation the conformation and activity of hHSF1.

PMID- 12796816
TI  - [Exogenous expression of SOCS box-deficient mutant ASB-8 suppresses the growth of
      lung adenocarcinoma SPC-A1 cells].
AB  - ASB-8 is a new member of the human ankyrin repeat and SOCS box containing protein
      family (ASB). This report deals with the expression of ASB-8 protein in lung
      carcinoma tissue, as well as its biological effect on the proliferation and
      growth of lung cancer cell line SPC-A1. ASB-8 was expressed in pT7-450 expression
      vector, and an anti-ASB-8 rabbit polyclonal antibody was prepared. The expression
      of ASB-8 protein in lung carcinoma tissue was detected using
      immunohistochemistry. The growth characteristics of the lung adenocarcinoma SPC
      A1 cells expressing either exogenous ASB-8 or ASB-8  SB (SOCS box-deficient) was
      studied by both in vitro cell growth curve and in vivo nude mouse tumor formation
      assay. Immunohistochemical staining detected positive reaction of 96.8% (30/31)
      showing that ASB-8 was highly expressed in lung cancer tissues; however, the
      expression of ASB-8 was lower, or even no expression in noncancerous lung
      tissues. Significant growth inhibition was observed in SPC-A1 cell line
      expressing ASB-8  SB on day 4 and persisted to day 6, compared with mock
      transfected cells (P<0.01). No difference in the growth properties was observed
      between ASB-8 and mock transfected cells. In vivo study also showed that tumor
      formation of ASB-8  SB expressing cells was significantly inhibited as compared
      with that of the control group (P<0.01). Therefore, ASB-8 may play an important
      role in growth and proliferation of lung cancer, possibly as positive regulator.

PMID- 12796818
TI  - The influence of oxygen-glucose deprivation on nitric oxide and intracellular
      Ca(2+) in cultured hippocampal neurons.
AB  - Nitric oxide (NO) was speculated to play an important role in the pathophysiology
      of cerebral ischemia. In this study, the effect of oxygen-glucose deprivation
      (OGD) on the cellular production of NO was investigated in cultured hippocampal
      neurons. Intracellular Ca(2+) was also detected as its closely relationship with
      NO. The generation of NO and changes in intracellular Ca(2+) were evaluated using
      confocal laser scanning microscopy with diaminofluorescein diacetate (DAF-2 DA),
      an NO probe, and Fluo-3, a Ca(2+) probe respectively. Extracellular glutamate
      level was also measured by HPLC with fluorescence detection. Results showed that
      OGD induced an increase in NO production and intracellular Ca(2+) concentration
      ([Ca(2+)](i)), the rise of DAF-2 and Fluo-3 fluorescence intensity was about 160%
      and 270% respectively; an increase of about 100% in glutamate level was observed
      after 20 min of OGD. NMDA inhibitor MK-801 significantly reduced the OGD-induced
      elevation of [Ca(2+)](i) and NO, DAF-2 and Fluo-3 fluorescence intensity uptake
      was inhibited by 69% and 74% respectively. The increase in NO production was also
      attenuated by extracellular Ca(2+) elimination and calmodulin (CaM) antagonist
      trifluoperazine dose-dependently. These results indicated that NO production
      increased during oxygen-glucose deprivation, and was greatly modulated by
      glutamate release, intracellular Ca(2+) change and Ca(2+)-CaM pathway.

PMID- 12796817
TI  - [Screening and identification of novel genes involved in biosynthesis of
      ginsenoside in Panax ginseng plant].
AB  - The root of Panax ginseng plant undergoes a specific developmental process to
      become a biosynthesis and accumulation organ for ginsenosides. To identify and
      analyze genes involved in the biosynthesis of ginsenoside, suppression
      subtractive hybridization (SSH) between mRNAs of 4- and 1-year-old root tissues
      was performed, and a subtracted cDNA library specific to 4-year-old roots was
      constructed. Forty cDNA clones selected randomly from the subtracted cDNA library
      were sequenced. Sequence information of all clones was evaluated by Nucleotide
      Blast analysis in GenBank/DDBJ/EMBL. The results showed that six subtracted cDNA
      clones represented the novel genes (ESTs), because no sequence homology with any
      known sequences was found in the database. Expression in 4-year-old P. ginseng
      root tissues was verified by reverse Northern dot hybridization for the six
      clones. These six novel genes were named GBR1, GBR2, GBR3, GBR4, GBR5, and GBR6,
      and their Accession numbers of GenBank are AF485334, AF485335, AF485336,
      AF485337, AF485332, and AF485333, respectively. Finally, Northern blot analysis
      and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR)
      confirmed that these six novel genes were differentially expressed in the defined
      development stage of P. ginseng plant roots. It is possible that their
      overexpression may play an important role in the ginsenoside biosynthesis. In
      addition, most of transcripts of all genes could also be detected in other P.
      ginseng plant tissues such as stem, leaf and seed. Our results provided a basis
      for obtaining the full-length cDNA sequences of such six novel genes, and for
      identifying their function involved in the biosynthesis of ginsenoside.

PMID- 12796819
TI  - Dynamic investigation of leukocyte-endothelial cell adhesion interaction under
      fluid shear stress in vitro.
AB  - To establish a method to investigate the dynamic adhesion between leukocytes and
      human umbilical vein endothelial cells (HUVECs) under definite shear stress. A
      parallel plate flow chamber system was developed to produce the definite shear
      stress in vitro. After the cultured HUVECs were loaded in the flow chamber, the
      circulation solution containing acridine orange (AO)-labeled leukocytes was
      perfused to flow through chamber at 0.71 dynes/cm(2). In this case, leukocyte
      endothelial cell adhesion process was induced. Lipopolysaccharide(LPS) was used
      as the chemical stimulus and dexamethasone(DXM) was used as the anti-inflammatory
      reagent. The adhesion process was recorded in videotape by Olympus IX70
      fluorescence microscope and CCD-camera. Then the number of adhesion leukocyte,
      slow and fast rolling velocities of leukocytes on the surface of HUVECs were
      measured based on the captured images. The number of static adhering and slow
      rolling leukocytes on the HUVECs treated with LPS was significantly increased by
      23.7-fold and 4.1-fold compared with that of the control group. Meanwhile, both
      the slow and fast rolling velocities of the leukocytes on HUVECs treated with LPS
      were significantly decreased by 25.6% and 26.1%. When HUVECs were treated with
      both LPS and DXM, the effect of LPS was inhibited obviously. This developed
      method can be used in studying ECs adhesion function affected by different
      chemical and physical stimulus and evaluating the various compounds interfering
      with cell adhesion.

PMID- 12796820
TI  - Improving the specific synthetic activity of a penicillin g acylase using DNA
      family shuffling.
AB  - Penicillin G Acylas (PGA) of Providencia rettgeri (ATCC 25599) was evolved using
      a modified DNA family shuffling method. The identity of pga genes from
      Escherichia coli, Kluyvera citrophila and Providencia rettgeri ranges from 62.5%
      to 96.9%. The pga genes from above three species were recombined and shuffled to
      create interspecies pga gene fusion libraries. By substituting assembled
      chimaeras for corresponding region of pETPPGA, different recombinants were
      constructed and expressed in E. coli JM109(DE3). Mutants with obvious beta-lactam
      synthetic activity were selected from the plates and the ratios of synthesis to
      hydrolysis (S/H) were determined subsequently. It was shown that the primary
      structures of selected positives exhibited significant diversity among each
      library. The best mutant possessed 40% higher synthetic activity than the wild
      type enzyme of PrPGA. It was further proved in this study that the domain of
      alpha subunit contributed much more to improve the specific activity of
      synthesis. Results showed a recombinant PGA with higher synthetic activity was
      acquired by the method of DNA shuffling.

PMID- 12796821
TI  - Factors affecting codon usage in Yersinia pestis.
AB  - The complete genome of Yersinia pestis which was the causative agent of the
      systemic invasive infectious disease classically referred as plague, had been
      recently sequenced. In order to have a further insight into the synonymous codon
      usage evolution, factors shaping synonymous codon usage pattern of Yersinia
      pestis were analyzed in this paper. The coding sequences larger than or equal to
      300 bp were used in codon usage analysis. Though "G"+"C" content in Y. pestis
      genome was slightly lower (47.64%), the highly expressed genes tended to use "C"
      or "G" at synonymous sites compared with lowly expressed genes. Conversely, lowly
      expressed genes tended to prefer "A" or "T" at synonymous positions. Gene
      expression level was strongly correlated with the first axis of the
      correspondence analysis (COA) (R=0.63, P<0.0001). By the analyses of the codon
      usage pattern of highly and lowly expressed genes, it was confirmed that gene
      expression level was partially responsible for the codon usage bias. GC-skew
      analysis showed that codon usage suffered replication-transcriptional selection.
      Codon adaptation index (CAI), frequency of "C"+"G" at the synonymous third
      position of codon (GC3s) and the effective number of codons (Nc) values showed
      some differences among different gene length groups. "G"+"C" content of genes was
      strongly correlated with the first axis of the COA (R=0.72, P<0.0001). It could
      be concluded that gene expressivity, replication-transcriptional selection, gene
      length and gene composition constraints were the main affecting factors of codon
      usage variation in Y. pestis.

PMID- 12796822
TI  - Morphology and morphogenesis of severe acute respiratory syndrome (SARS)
      associated virus.
AB  - After infecting the Vero E6 cells by nasal/throat swabs collected from SARS
      patients, we studied the SARS-associated virus by electron microscopy and
      molecular biological technique. The results show that the diameter of newly
      isolated virus is about 50 nm without envelope or 100 nm with envelope. The virus
      was proved to be a new coronavirus by RT-PCR and it responded positively to
      convalescent-phase serum specimen from SARS patients, which is the evidence that
      this new virus is etiologically linked to the outbreak of SARS. The morphogenesis
      and distribution of the virus are also discussed in this article.

PMID- 12796823
TI  - [Holographic recording properties of BR-D96N film].
AB  - BR-D96N was a genetically mutated product of bacteriorhodopsin (BR) with obvious
      improved photochromic effect. Compared with the wild type BR, BR-D96N had a
      lifetime of M state prolonged to 5 min, showing obvious saturation absorption and
      lower light intensity in saturation absorption (0.4 mW/cm(2)). In case of
      holographic recording, dynamic grating was recorded in the BR-D96N film, its
      characteristic parameter was not light exposure energy but light intensity. The
      writing time of the holographic grating depended on the recording light
      intensity. The higher the recording light intensity, the faster the grating
      builds up. Under a weak reconstruction light, the recording light intensity
      resulting in maximal diffraction efficiency was consistent with the saturation
      absorption intensity. The reconstruction light could partly erase the grating.
      With lower intensity of reconstruction light, higher diffraction efficiency
      (1.8%) could be reached, but the diffraction intensity was not high. To get
      highest diffraction intensity, a properly high intensity of reconstruction light
      was needed (80 microW/cm(2)). The result of these experiments showed that
      holographic images could be recorded on the BR-D96N film.

PMID- 12796824
TI  - Chronic meningitis: still a diagnostic challenge.
AB  - Chronic meningitis is characterized by a progressive, subacute onset of
      lepomeningeal disease and persisting cerebrospinal fluid (CSF) abnormalities such
      as elevated protein level and pleocytosis for at least one month. The array of
      aetiologies is very wide comprising non-infectious (carcinomatous, systemic
      disease, toxic) and infectious (classic and opportunistic pathogens). The
      evaluation encompasses a careful history, complete physical examination and
      laboratory tests. The specific diagnosis may remain a challenge in some cases.
      Algorithms for the differential diagnosis are provided for both immunocompetent
      and immunocompromised patients.

PMID- 12796825
TI  - Clinicopathological and molecular characterization of neuronal ceroid
      lipofuscinosis in the Portuguese population.
AB  - A series of 53 Portuguese patients (derived from 43 families) born in the period
      1963-1999 have been diagnosed with neuronal ceroid lipofuscinosis (NCL) based on
      clinicopathological findings. Plotting the cumulative number of new cases per
      year against the year of birth resulted in a slightly S-shaped curve, with a
      nearly straight central segment over a period of 14 years (1977-1990) indicating
      a continuous registration of new cases born during the corresponding time period.
      In this period the prevalence of overall NCL in the Portuguese population was
      calculated to be 1.55 per 100.000 live births.Twenty-six patients from 20
      unrelated families were further evaluated by combining clinicopathological with
      biochemical and genetic data. No intra-familial heterogeneity was observed. Four
      sub-types of childhood NCL were identified: infantile NCL (INCL) with granular
      osmiophilic inclusions (GROD) and PPT1 deficiency (1/26), classical LINCL with
      curvilinear (CV) inclusions and tripeptidyl peptidase (TPP1) deficiency (3/26),
      variant late infantile NCL (LINCL) with fingerprint/curvilinear (FP/CV)
      inclusions and normal TPP1 enzyme activity (11/26) and juvenile NCL (JNCL) with a
      mix of FP/CV (11/26). Eight of 11 JNCL patients were homozygous for the 1.02-kb
      deletion in the CLN3 gene, and 3 were heterozygous with an unidentified mutation
      in the second allele. The 1.02-kb deletion in the CLN3 gene accounted for 86.3 %
      (19/22) of CLN3-causing alleles and 36.5 % (19/52) of childhood NCL defects. The
      causal mutations for CLN1 and CLN2 were V181M (2/2) and R208X (4/6),
      respectively. CLN1, CLN2 and CLN3 affected 3.8 %, 11.5 % and 42.3 % of NCL
      Portuguese patients, respectively. In 42.3 % of patients affected by the vLINCL
      form, CLN3, CLN5 and CLN8 gene defects were excluded by direct sequencing of
      cDNA. Genetic variants such as CLN6 might therefore cause a significant portion
      of childhood NCL in the Portuguese population. The relative frequency of
      classical childhood forms of NCL in the Portuguese population is reported and
      contributes to the knowledge of genetic epidemiology of these world-widely
      distributed disorders.

PMID- 12796826
TI  - Refinement of the spinocerebellar ataxia type 4 locus in a large German family
      and exclusion of CAG repeat expansions in this region.
AB  - Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant disorder mapped to
      chromosome 16q22.1 in a large Utah kindred. The clinical phenotype is
      characterized by cerebellar ataxia with sensory neuropathy. We describe a five
      generation family from northern Germany with similar clinical findings linked to
      the same locus. Haplotype analyses refined the gene locus to a 3.69 cM interval
      between D16S3019 and D16S512. Analysis of nine CAG/CTG tracts in this region
      revealed no evidence for a repeat expansion.

PMID- 12796827
TI  - Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple
      sclerosis.
AB  - Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be
      of autoimmune origin the correlation of these two diseases is of special
      interest. The aim of this study was to determine whether there are differences in
      the prevalence of thyroid disease with special emphasis on AIT compared with MS
      and normal subjects and whether the presence of thyroid disease correlates with
      disability, disease course, age, and disease duration. 353 consecutive patients
      with clinically definite MS, without interferon-beta treatment and 308 patients
      with low back pain or headache were extensively examined for the presence of non
      immune or autoimmune thyroid disease. We found a significantly higher prevalence
      of AIT in male MS patients (9.4 %) than in male controls (1.9 %; p = 0.03). The
      prevalence of AIT in female MS patients (8.7 %) did not differ from female
      controls (9.2 %). Hypothyroidism, caused by AIT in almost all cases, showed a
      tendency to be more severe and more often present in patients with MS. There was
      no association between relapsing-remitting and secondary progressive disease
      course of MS and the prevalence of AIT. MS patients with AIT were significantly
      older but did not differ in disease duration and expanded disability status scale
      (EDSS). Further studies are warranted, to see if there is a difference in sex
      hormone levels between MS patients with and without AIT and healthy controls.
      Longitudinal studies comparing MS patients with or without AIT could show whether
      there is an influence of AIT on the disease course or progression.

PMID- 12796828
TI  - Does age influence early recovery from ischemic stroke? A study from the Hessian
      Stroke Data Bank.
AB  - Age is the most important risk factor for developing a stroke. In addition, age
      may also influence stroke recovery. To allow structured discharge planning, it
      may be important to consider the influence of age on stroke recovery during the
      early phase. We studied the effect of patient age on early stroke recovery in a
      cohort of 2219 unselected stroke patients. Data on functional status (Barthel
      Index Score) were collected prospectively within 24h after admission, after one
      week and at discharge for 2219 acute stroke patients treated in 1999 and 2000 at
      7 neurological departments in the county of Hesse, Germany. Multiple regression
      analyses were used to test for an association between age, relative recovery and
      speed of recovery of ADL after stroke. More than half of the patients (58 %)
      improved in functional status during hospitalization. 37 % had no change in
      Barthel Index score and only a small number of patients (5 %) deteriorated during
      this period. Relative improvement decreased with increasing age: patients younger
      than 55 years showed an improvement of 67 % of the maximum possible improvement
      compared whith only 50 % for patients above 55 years (adjusted R(2) = 0.120,
      beta(age) = -0.130, p < 0.001). Age only had a small effect on the speed of
      recovery. For younger patients functional recovery was slightly faster (adjusted
      R(2) = 0.256, beta(age) = -0.080, p < 0.001). Despite its strong influence on
      case fatality, age is a poor predictor of functional recovery during the very
      early phase after stroke. Resulting functional recovery depends much more on the
      extent of the initial disability. Advanced age should not be regarded as a
      limiting factor in the early rehabilitation of stroke patients.

PMID- 12796829
TI  - Diabetic neuropathy in patients with "latent autoimmune diabetes of the adults"
      (LADA) compared with patients with type 1 and type 2 diabetes.
AB  - OBJECTIVE: In previous studies, a lower incidence of diabetes-related
      complications such as diabetic neuropathy has been reported in patients with
      early stages of type 1 diabetes compared with type 2 diabetes. The aim of this
      study was to compare the prevalence of diabetic neuropathy in patients with
      manifestation of a slow onset type 1 diabetes in adulthood - latent autoimmune
      diabetes in adults (LADA) - with classical type 1 and type 2 diabetes patients.
      RESEARCH DESIGN AND METHODS: Altogether, 37 patients (14 LADA, 9 type 1 and 14
      type 2 diabetes) with short term diabetes (duration < 5 years) were investigated
      for diabetic neuropathy on the basis of clinical and neuroelectrophysiological
      evaluations. The neurological functions were evaluated by a standardized
      questionnaire and clinical examination. In electrophysiological evaluations the
      different nerve fibres were investigated using motor and sensory nerve conduction
      studies, quantitative thermotesting, vibratometry and autonomic function tests
      (heart rate variability). RESULTS: LADA patients had a significantly lower
      clinical examination score (p = 0.008), cardiorespiratory reflex index (p =
      0.009) and cold perception threshold index (p = 0.004). The neurological symptom
      score, the indices of motor and sensory nerve conduction, the index of
      thermotesting (warm perception threshold) and the vibratometry showed a trend to
      higher values in LADA patients than in type 2 diabetes patients. There were no
      significant differences between LADA and type 1 diabetes patients. CONCLUSIONS:
      LADA patients had fewer features of diabetic neuropathy than type 2 diabetes
      patients in the early stages of disease, thus being more similar to classical
      type 1 diabetes patients who normally develop diabetic neuropathy rather late.

PMID- 12796830
TI  - The 129 codon polymorphism of the prion protein gene influences earlier cognitive
      performance in Down syndrome subjects.
AB  - Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a
      methionine (M) for valine (V) substitution at codon 129 has been associated with
      cognitive impairment in elderly individuals. Down syndrome (DS) is associated
      with mental retardation and development of Alzheimer-like brain abnormalities. In
      the present study, we investigated the role of the PRNP polymorphism in 122
      relatively young Italian DS patients. Allele frequencies of DS subjects did not
      differ from those in the general population. However, we found a significantly
      faster rate of decline in intellectual ability in the subgroup of DS patients
      carrying at least one V allele compared with the M/M DS subjects. An additive
      deleterious effect of apolipoprotein E epsilon 4 allele was detected after
      stratifying by APOE gene status. Our findings provide evidence that variability
      of the PRNP gene at codon 129 might contribute to accelerating the rate of
      earlier cognitive decline in DS subjects.

PMID- 12796831
TI  - Effects of the oral form of ondansetron on cerebellar dysfunction. A multi-center
      double-blind study.
AB  - The aim of this study was to assess the efficacy and the safety of ondansetron
      administered orally in patients with a cerebellar disorder. The study was a
      randomised, multi-center, double-blind trial. The patients were randomised either
      to oral ondansetron 8 mg or to placebo twice daily for seven days. Cerebellar
      dysfunction was quantified before and after treatment using the International
      Cooperative Ataxia Rating Scale (ICARS). We performed a global analysis (total
      scores), we analysed by subscores (4 subscores: oculomotor, speech, kinetic,
      postural) and subgroups (4 subgroups: Cerebellar Cortical Atrophy (CCA), Multiple
      Systemic Atrophy (MSA), Familial Cerebellar Degeneration (FCD) and miscellaneous
      cerebellar disorders), and we also performed an analysis by individual test
      items. We investigated whether ondansetron and placebo had different effects upon
      ICARS total scores and subscores in the 4 subgroups considered together or
      separately. For p values < 0.05, we subsequently applied the Mann-Whitney test to
      compare ondansetron and placebo effect for each individual item. We evaluated 45
      of the 46 patients included. No effect was found in global analysis. We found no
      difference in the analysis of the ICARS subscores. Concerning the individual test
      items, there was a significant difference between the placebo and ondansetron for
      the finger-to-nose test (p = 0.049), the Heel-to-Knee test (HK); (p = 0.03), the
      Body Sway Eyes Closed (p = 0.017) and the Body Sway Eyes Open (BSEO); (p =
      0.014). There was no significant difference for tremor in upper limbs (p = 0.32)
      or for gait (p = 0.49). The Mann-Whitney test showed a greater effect of
      ondansetron than placebo for BSEO in miscellaneous disorders (p = 0.013) and for
      HK in FCD (p = 0.036), but ondansetron was deleterious for HK in CCA (p = 0.019).
      Our study showed no effect of oral ondansetron on global cerebellar dysfunction.
      The analysis by subgroups showed that the oral form of ondansetron (a) is
      deleterious for coordination in patients with CCA, (b) has no effect upon tremor
      in upper limbs, and (c) has a mild effect upon posture and coordination in lower
      limbs in some subgroups of ataxic diseases.

PMID- 12796832
TI  - The epidemiology of myasthenia gravis, Lambert-Eaton myasthenic syndrome and
      their associated tumours in the northern part of the province of South Holland.
AB  - We studied the epidemiology of myasthenia gravis (MG) and the Lambert-Eaton
      myasthenic syndrome (LEMS), and their association with small cell lung carcinoma
      (SCLC) and thymoma, in a well defined region of the Netherlands. Available data
      on all the patients with MG, LEMS, thymoma or SCLC living between 1 January 1990
      and 31 December 1999 in the northern region of South Holland, with a population
      of 1.7 million inhabitants, were evaluated. A total of 202 patients with MG (20
      with thymoma) and ten patients with LEMS (seven with SCLC) were identified. LEMS
      was 46 times less prevalent (2.32 x 10(-6)) than MG (106.1 x 10(-6)), whereas the
      annual incidence rate of LEMS was 14 times lower (0.48 x 10(-6)) than of MG (6.48
      x 10(-6)), reflecting the poor survival of LEMS patients with SCLC. SCLC was
      diagnosed in 1593 patients, seven (0.44 %) of whom developed LEMS. Mean age at
      diagnosis of SCLC was significantly lower in SCLC patients with LEMS (p = 0.006).
      A thymoma was diagnosed in 32 patients, of whom the ten patients with MG (31 %)
      had a younger age at diagnosis of thymoma than the patients without MG (p =
      0.27). This study confirms the increasing prevalence of MG over the last few
      decades as reported by others, and underscores the relative rarity of LEMS. The
      frequency of LEMS in our patients with SCLC was lower than reported in previous
      studies. In patients with a SCLC or thymoma, the tumour was diagnosed at younger
      age in those who had the associated myasthenic syndrome.

PMID- 12796833
TI  - Central-peripheral sensory axonopathy in a juvenile case of Alpers-Huttenlocher
      disease.
AB  - Peripheral ataxia is reported in a juvenile case of Alpers-Huttenlocher disease
      (AHD). Neurophysiological and neuropathological investigations revealed a central
      peripheral axonopathy, affecting the deep sensation carried by the peripheral
      nerve fibres and the posterior tracts of the cord, due to neuronal loss of the
      sensory ganglia. Involvement of the sensory pathways is regarded as a major
      feature of juvenile AHD.

PMID- 12796834
TI  - Thalamic stimulation for tremor. Subtle changes in episodic memory are related to
      stimulation per se and not to a microthalamotomy effect.
AB  - The aim of this study was to investigate the impact of unilateral deep brain
      stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on
      neuropsychological functioning comparing stimulation-on with stimulation-off
      conditions. Nine patients [five patients with Parkinson's Disease (PD), two
      patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)]
      underwent comprehensive neuropsychological testing for cognitive functions,
      including general mental impairment, aphasia, agnosia, executive and
      constructional abilities, learning, memory, cognitive processing speed and
      attention as well as depression. The neuropsychological assessments were
      performed at least 6 months postoperatively (mean 9 months). Testing in the
      stimulation-on and stimulation-off condition was obtained within a period of 3 to
      4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There
      were no significant differences between the stimulation-on and the stimulation
      off condition with the exception of a decrement of word-recall in the short delay
      free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup
      analysis indicated that the impairment in word-recall was related to left-sided
      thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe
      method with regard to cognitive function. The subtle changes in episodic memory
      are related to stimulation per se and not to a microthalamotomy effect.

PMID- 12796836
TI  - Short latency trigemino-sternocleidomastoid response in patients with migraine.
AB  - OBJECTIVE: To investigate the central trigeminal circuits in migraine patients.
      MATERIALS AND METHODS: Short latency responses can be recorded in
      sternocleidomastoid (SCM) muscles after stimulation of the trigeminal nerve
      (trigemino-cervical reflex). This brainstem reflex was investigated in 20 healthy
      subjects, in 20 patients suffering from migraine with aura (MWA) and in 20
      patients suffering from migraine without aura (MWOA) during and between the
      attacks. RESULTS: The trigemino-cervical responses were bilaterally abnormal in
      17 patients with MWA and 15 patients with MWOA during the headache attacks, in 11
      patients with MWA and in 10 patients with MWOA during the interictal period. In
      the patients with normal trigemino-cervical responses during the pain-free phase
      the triptan was significantly more effective at relieving headache. CONCLUSIONS:
      Our findings further support and emphasise the role of the trigeminal system in
      the pathogenesis of migraine. The bilateral location of the abnormalities
      suggests a centrally located dysfunction. Therefore, the trigemino-cervical
      reflex is sensitive in disclosing a disturbed brainstem activity and may be an
      index of neuronal activity in the human brainstem; moreover their assessment may
      help as valuable prognostic tool for predicting the efficacy of triptans therapy.

PMID- 12796835
TI  - Chronic dysimmune neuropathy. A subclassification based upon the clinical
      features of 102 patients.
AB  - The Chronic Dysimmune neuropathies (CDN) are a clinically heterogeneous group of
      polyneuropathies united by their presumed immune mediated aetiology. At present
      such neuropathies are classified as Chronic Inflammatory Demyelinating
      Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN) and the Neuropathies in
      association with serum Paraproteins (Paraproteinaemic Neuropathies). This
      classification fails to recognise other distinctive syndromes and is limited by
      heterogeneity within, and overlap between, subgroups. We have refined this
      clinical subclassification by a review of a consecutive series of 102 unselected
      patients with CDN referred to a single neurologist. We recognise 6 clinical
      subtypes of CDN: one sensory ataxic group; three motor-sensory subgroups (chronic
      motor sensory demyelinating neuropathy, subacute motor sensory demyelinating
      neuropathy and a multifocal motor sensory neuropathy); and two pure motor
      subgroups (symmetric pure motor demyelinating neuropathy and multifocal motor
      neuropathy). This subclassification allows distinct syndromes to be recognised
      and helps resolve problems of heterogeneity and overlap. Distinction between
      these subgroups is of immediate practical relevance to patient management.
      Although steroids are beneficial for most of the subgroups, this is not so for
      both of the pure motor syndromes which should be treated with intravenous
      immunoglobulin. Patients with chronic development of Motor Sensory Demyelinating
      Neuropathy respond less well to steroids than those with a subacute onset. An
      association was found between elderly patients with Subacute Motor Sensory
      Demyelinating Neuropathy and carcinomas. Within any clinical subgroup patients
      behave similarly regardless of the presence of associated paraproteins or nerve
      specific antibodies.

PMID- 12796838
TI  - Subjective visual vertical and Romberg's test correlations in hydrocephalus.
AB  - OBJECTIVE: Exploration of the subjective visual vertical in pitch and Romberg's
      test in patients with hydrocephalus. Patients Eleven patients with communicating
      normal pressure hydrocephalus and six with non-communicating hydrocephalus due to
      aqueductal stenosis were examined before and after surgical treatment. METHODS:
      The subjective visual vertical was examined with a simple, custom-made
      articulated rod. The rod was faintly illuminated from within so as to appear
      floating in space when presented in darkness. The test task was to manually
      adjust the rod's position in pitch so that it appeared perfectly vertical.
      Romberg's test was performed under standardized conditions. RESULTS: Patients
      with a backward movement on Romberg's test showed a deviation of the subjective
      visual vertical, tilting the upper end of the rod closer to their eyes. Patients
      moving in other directions tilted the rod in the opposite direction (p < 0.01).
      The time in which the patients managed Romberg's test with open eyes correlated
      with the intratest variability of rod placement (r = 0.86, p < 0.001). After
      surgery, improvements on Romberg's test correlated with a decreased intratest
      variability of the subjective visual vertical. There were no differences between
      the two patient groups. CONCLUSIONS: Quantitative measurements of the subjective
      visual vertical in pitch correlate strongly with results of Romberg's test in
      patients with hydrocephalus.

PMID- 12796837
TI  - Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a
      Jewish family.
AB  - BACKGROUND: Frontotemporal dementia with parkinsonism linked to chromosome 17q21
      22 (FTDP-17) is an autosomal dominant tauopathy manifested by a variable
      combination of personality changes, cognitive decline and hypokinetic-rigid
      movement disorder. Significant clinical and pathological heterogeneity of FTDP-17
      is related in part to more than 20 different pathogenic mutations identified in
      the tau gene. Among others, the P301S mutation has been previously reported in
      three families of European and one of Japanese origin presenting with different
      clinical phenotypes. OBJECTIVES: To report a three-generation family of Jewish
      Algerian origin with FTDP-17 due to the P301S tau mutation. METHODS: Clinical,
      neuropsychological and neuroimaging evaluation of 3 patients, tau genotyping, and
      pathological study of the proband. RESULTS: The 3 affected family members had a
      fairly stereotyped clinical course with early personality changes from their late
      30s followed within a period of 1-2 years by a progressive cognitive and motor
      deterioration eventually leading to a state of akinetic mutism or death 3-5 years
      after the initial symptoms. The main clinical manifestations included severe
      dementia and hypokinetic-rigid movement disorder associated with supranuclear
      gaze impairment, pyramidal signs and frontal release signs. Brain imaging
      disclosed a variable degree of frontotemporal atrophy, ventriculomegaly and
      regional cerebral hypoperfusion or glucose hypometabolism. Frontal lobe biopsy in
      the proband revealed weak tau immunoreactivity in a few cortical neurons, in rare
      neurites and in some glial cells with no neurofibrillary tangles. Molecular DNA
      analysis identified a P301S mutation in exon 10 of the tau gene. CONCLUSIONS: The
      observed clinical features further expand the reported P301S phenotype and
      confirm a more aggressive course of the disease than in the other known tau
      mutations.

PMID- 12796840
TI  - [Coping of diseases in old age--partnership as a resource].
AB  - Somatic as well as mental health of the elderly are to a high extent determined
      by the quality of their marriage, the reciprocity of social support, and the
      available socio-economic resources. The coping behavior does not change very much
      in the course ofa person's life. If he or she has sufficient skills and
      resources, the elderly person will engage in problem-focused coping. If demands
      are appraised as outside of the person's control, secondary control strategies
      aiming at a reappraisal are more frequently applied. A crucial coping resource in
      old age is the availability of social support that is experienced as adequate and
      useful by the recipient. The spouse and members and close family members are the
      most important sources of social support for the elderly.

PMID- 12796839
TI  - A prospective trial of mechanical physiotherapy for lumbar disk prolapse.
AB  - Fifty consecutive patients with neuroradiologically confirmed lumbar disk
      prolapse, who responded to the first five daily physiotherapy sessions with pain
      centralization, were prospectively treated with mechanical physiotherapy
      (McKenzie). At a median follow-up of 55 weeks, there were high rates of patient
      satisfaction, recovery from neurological deficits, and employment, and a low rate
      of surgical interventions. Mechanical physiotherapy is thus a useful diagnostic
      tool and an effective treatment strategy for many patients with lumbar disk
      disease.

PMID- 12796841
TI  - [Wishes and possibilities in the face of limited resources].
AB  - The main intention of health economic studies is to find out how to cope with the
      prevailing scarcity of resources. But scarcity is comparable to morbidity. As
      morbidity can not be finally cured by medical intervention, the problem of
      scarcity can only be solved relatively by economic research. It is evident, that
      the sensation of scarcity even aggravates with increasing prosperity. That is
      because human demands do in fact outrun economic potentials. The scarcity of
      resources therefore demands for setting of priorities. That is what economics in
      general and health economics in particular has set rules for. Priorities can be
      set by the state, the market or joint associations. The prevailing system in
      Germany is based on associations, the so called self-governing body. The scare
      financial resources are divided into budgets and allocated to service suppliers
      following predefined negotiation mechanisms within the joint self-administration.
      In recent years an increasing paternalism of the German government on the joint
      self-administration can be observed. Although Germany spends more on healthcare
      than ever before, the scarcity is noticed as threatening. The government
      currently interferes to cope with this problem. In opposition to that approach
      critics postulate more individual freedom in decisions for insurance holders,
      patients, health insurances and suppliers. The principal of subsidiarity intends
      to strengthen self-responsibility in the health care sector while in return the
      principle of solidarity within the legal health insurance is reduced.

PMID- 12796842
TI  - [Angiogenesis, lymphangiogenesis, and tumor progression].
AB  - Angiogenesis plays an important role for the growth and metastasis of malignant
      tumors. The "angiogenic switch" may even precede the development of other traits
      that contribute to the malignant phenotype. The switch to the angiogenic
      phenotype is thought to be induced by a change in the balance of positive and
      negative regulators of angiogenesis. The main emphasis of this review is to
      discuss the role of two potent endogenous inhibitors, thrombospondin-(TSP-)1 and
      TSP-2, for the development and progression of tumors. The recent identification
      of specific growth factors for lymphatic vessels and of new lymphatic-specific
      markers provided evidence for an active role of the lymphatic system during the
      metastasis process. Endogenous inhibitors of lymphangiogenesis have not yet been
      detected and until recently it was unclear whether or not the known endogenous
      angiogenesis inhibitors may also have some additional effects on
      lymphangiogenesis. The data provided indicate that angiogenesis inhibitors
      specifically inhibit tumor progression but fail to block the conversion of
      premalignant to malignant tumors. Moreover, angiogenesis inhibitors may have some
      elective effects on the formation of blood vessels but not on lymphatic vessels.
      These results will have implications for the further development and clinical use
      of angiogenesis inhibitors since they indicate that inhibitors might most
      efficiently be used to target early stages of tumor progression and in
      combination with specific inhibitors of lymphangiogenesis.

PMID- 12796843
TI  - [Diagnosis and therapy of uterine sarcoma].
AB  - Radical surgery in stage I and II uterine sarcoma removing all tumor
      manifestations is the only curative therapy option for early stage disease.
      Larger tumors (> 4 cm) and the presence of lymph node metastasis correlate with a
      high local recurrence rate. For these tumors adjuvant radiation and/or adjuvant
      chemotherapy may be recommended after surgical therapy. Adjuvant therapy however,
      should preferably be considered for uterine stromal sarcomas and mixed mesodermal
      tumors. The toxicity of radiation and/or chemotherapy is greater than any
      possible benefit for patients with leiomysarcomas as these tumors rarely respond
      to radiation or chemotherapy. For advanced (> stage I and II) and recurrent
      disease, curative therapy options are not available and palliative therapy for
      these patients has to take into consideration the negative side effects and weigh
      up quality of life against an often very limited possible benefit of such
      therapy.

PMID- 12796844
TI  - HPV induced cervical carcinogenesis: molecular basis and vaccine development.
AB  - Association of infection with papillomavirus and dysplasia of the cervix uteri
      has been firmly established. There are only few cervical cancers where no HPV DNA
      is detectable. The mechanism of epithelial cell immortalization by interaction
      with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is
      elucidated. Progression of the HPV infected cell to a malignant phenotype
      involves further modification of host gene expression and/or mutations. The
      appearance of chromosomal aberrations can lead to mutational inactivation or loss
      of tumour suppressor genes (TSG), activation and amplification of oncogenes, with
      importance for the process of carcinogenesis. Oncogene amplification, with
      exception of few reports, seems not to be a major mechanism in cervical
      carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results
      from CIN and invasive cancer demonstrate alterations at specific chromosomal
      regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p,
      6p, 1lq were frequently found early in tumour development Primary invasive
      carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q.
      Useful biological diagnostic and prognostic markers for high-risk HPV infection
      and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative
      senescence genes relevant for HPV-induced carcinogenesis are localized on
      chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located
      on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist
      Therefore, immune therapy is an attractive possibility for prevention and therapy
      of HPV infection. To date, vaccine development has reached clinical evaluation.
      Prophylaxis aims at the induction of virus neutralizing antibodies to capsid
      proteins. Virus-like particle vaccines are currently tested in clinical trials.
      Due to the long lag period between infection and clinical manifestation trials
      will take a long time until conclusive results are obtained. Mandatory expression
      of viral and perhaps certain cellular genes in infected epithelial and tumour
      cells offers targets for therapeutic approaches. Since most dysplasia clears
      spontaneously the viral infection is immunogenic to some extent. However, in some
      individuals the immune response has to be stimulated by vaccination in order to
      be effective. Several strategies are being tested in clinical trials and others
      are in preclinical development The task will be to circumvent immunosuppressive
      features of the HPV infected cells.

PMID- 12796845
TI  - [Breastfeeding nursing after breast surgery].
AB  - Beside breast cancer and benign tumors the majority of breast surgery is
      performed in a fertile age. This leads to the question about breastfeeding after
      breast surgery. Theoretically reduction mammaplasty and augmentation shouldn't
      impair the ability to nurse, as long as there is no free transplantation of the
      mamilla-areola-complex or an ablation of the breast. The average frequency of
      nursing after reduction mammaplasty among five studies is about 31 %. A
      frequently named reason not to nurse is the discouragement by the health care
      provider. Women treated with breast cancer should be encouraged to breastfeed
      their children. The goal of this publication is to give a review on the
      contemporary literature to this rarely discussed and examined topic.

PMID- 12796846
TI  - [Stem cell procedures on a legal point of view].
AB  - Stem cell procedures could be the starting point for major advances in
      healthcare. However, it is a very difficult task to define the legal status of
      human stem cells. The resolution of the legal issues has been hindered by the
      still early stage of research and development and by scientists' varying
      assessment of the fundamental differences between several types of stem cells and
      of the potential of these types. Nevertheless, on 30 January 2002 the German
      Parliament (Bundestag) paved the way for the import of pluripotent embryonic
      cells under the following basic conditions: The import is restricted to stem cell
      lines which already exist; the embryo's parents' informed consent has to be
      obtained; the research purposes must be high-ranking; the ethical acceptance has
      to be examined by a high-level ethical committee; and an authorizing authority
      must license the import. The questions is, whether these requirements meet the
      practical needs of scientists. However, the European Biotechnology Directive
      calls for the patentability of stem cell procedures and therefore presents a
      major incentive for researchers in the field of stem cell technologies.

PMID- 12796848
TI  - [A systematic comparison of national and international dementia guidelines].
AB  - Several guidelines for the evidence-based diagnosis and treatment of dementing
      disorders have been published in Germany and worldwide during the last years.
      This review analyses the content and methodological quality of 13 recently
      published dementia guidelines. There are some unequivocal recommendations for
      diagnostic procedures (e. g. clinical evaluation, neuropsychological screening,
      structural brain imaging) and treatment (e. g. cholinesterase inhibitors). There
      is a broad range of opinions on other procedures (e. g. routine EEG, FDG PET,
      cognitive training). A discussion of the prevalent guideline pluralism and a
      pleading for regionally adapted international guidelines conclude this article.

PMID- 12796847
TI  - [The concentration of carnitine in the last trimester of pregnancy subject to
      glucose tolerance].
AB  - OBJECTIVE: In this study the correlations between the concentration of carnitine
      and an increasing glucose intolerance in women with untreated, non insulin
      dependent gestational diabetes (GDM) were examined. METHODS: 129 pregnant women
      were challenged with an oral 75 gm glucose load in the last trimester. Patients
      were assigned to five different groups with increasing glucose intolerance
      depending on the maximal glucose level after glucose challenge. Blood samples for
      measurement of free and acyl carnitine (spectrophotometric method) were taken
      prior to glucose evaluation. RESULTS: In correlation with increasing glucose
      intolerance concentration of acyl carnitine rose from 3.43 +/- 1.62 micromol/l
      (normal glucose tolerance) to 4.62 +/- 1.93 micromol/l (gestational diabetes)
      while free carnitine decreased from 12.17 +/- 2.71 micromol/l to 11.52 +/- 2.90
      micromol/l (p > 0.05). The quotient of acyl carnitine/free carnitine was
      significantly higher in women with GDM than in women with normal glucose
      tolerance. CONCLUSION: Due to the high overlap of results, carnitine isn 't
      suitable for further differentiation of glucose metabolism or to evaluate the
      efficacy of therapy in non insulin dependent GDM.

PMID- 12796849
TI  - [Botulinum toxin in tension-type headache].
AB  - Botulinum toxin has meanwhile been approved for a number of indications. It is
      also gaining acceptance in other indications with a major focus on pain. The most
      common type of headache is tension-type headache (TTH) the pathogenesis of which
      has not yet been unfolded. As it looks there are vascular, myofascial and
      supraspinal factors intertwined. It is felt that headache is triggered by
      myofascial stimuli. The application of botulinum toxin is an intelligent
      alternative since the favorable effect of pharmacologic and other therapies is
      limited. Application of BTX should be considered when the pericranial muscles are
      involved. One of the effects produced lies in the reduction of muscular stress,
      muscular ischemia and muscle tone. We still don't know whether additional
      mechanisms such as retrograde uptake and direct antiinflammatory potential are
      involved. Current data permit the conclusion that headaches are decreased in
      their frequency and distinctiveness. Significant untoward effects are not to be
      expected. Neither the ideal dose nor the optimum selection of injection sites
      have been established as yet, an individual injection scheme is apparently most
      promising. Injection of the trigger points seems to make sense.

PMID- 12796850
TI  - [Diagnosis, treatment and progress after frontal lobe injury].
AB  - The comprehensive assessment of a frontal lobe injury is one of the most complex
      problems in diagnosis and treatment due to the variability of nature, extent and
      effect of various disorders of higher cerebral functions, i. e. impairment of the
      ability to act systematically, attention, motivation and emotionality. This
      brings about considerable differences in assessing and judging the effects of
      frontal lobe syndromes. Impairments of initiation, planning and carrying out of
      actions, of impulse control, attention, memory and self-perception often manifest
      in disorganised and dissocial behaviour which brings about serious effects in
      many fields of social adaptability. Deeper neurological insights in nature and
      effects of these deficiencies and improved diagnostical methods and concepts of
      intensive-care treatment as well as the improved understanding in the necessity
      of a longterm rehabilitation program have led to the development of specific
      strategies concerning the dealing with the patient, the counseling of the social
      environment, especially of the relatives, and the treatment of the patient's
      symptoms. In the course of acute and rehabilitative treatment the patient
      normally has to develop strategies of habituation and adaptation to his social
      environment, furthermore techniques of compensation as well as an improvement of
      personal resources including attention, memory and planning of actions. The
      ability of self-control ought to be improved by training of behavioural
      strategies leading to an increased independence. The success of treatment varies
      distinctly from individual to individual. As a rule, basic capabilities in the
      scope of higher brain functions as well as executive and behavioural abilities
      can be improved. However, a restitutio ad integrum of all dysfunctions is very
      rare.

PMID- 12796851
TI  - [Diabetes mellitus type II--induced by "atypical" neuroleptics?].
AB  - After the introduction of the so-called "atypical antipsychotics" in the clinical
      practice hyperglycemia as well as increased triglyceride and cholesterol serum
      levels were reported in patients treated with some of these agents. The studies
      and case reports available up to now were reviewed. Some epidemiologic studies
      show that diabetes mellitus occurs more often in patients treated with atypical
      antipsychotics if compared to conventional antipsychotics. The available data
      show that hyperglycemia and diabetes mellitus type II were particularly observed
      in patients receiving clozapine and olanzapine. Also diabetic ketoacidosis was
      most frequently reported in patients treated with these drugs. The underlying
      pathomechanism still remains widely unclear. There is some evidence for an
      important role of insulin and also leptin. Their secretion seems to be influenced
      by some atypical antipsychotics. Since overweight is a known risk-factor for
      diabetes mellitus type II, the weight inducing effect of atypical antipsychotics
      may also play an important role. Since diabetes mellitus type II often lead to
      severe diseases, the serum glucose levels should be paid more attention in the
      treatment with atypical neuroleptics.

PMID- 12796852
TI  - [Temperament and affective disorders--historical basis of current discussion].
AB  - The history of the temperament concept begins in ancient Greece. The humoral
      theory remained influential over the centuries. At the beginning of the 20 th
      century, both Wilhelm Wundt and his pupil Emil Kraepelin formulated new aspects.
      Wundt described two dimensions: "speed of variability of emotions" and "intensity
      of emotions". Kraepelin observed four fundamental states (depressive, manic,
      irritable and cyclothymic), which he linked to manic-depressive illness. Since
      then different lines of temperament research have evolved: (1) psychiatric
      psychopathological theories (e. g. Ewald, Kretschmer and Sheldon), which tend to
      see temperament as a dilution of full-blown affective disorders; (2)
      neurobiological theories (e. g. Pavlov, Eysenck and Gray), which understand
      temperament as determined by underlying neurobiological processes - especially
      levels of arousal; and (3) developmental theories (e. g. Chess & Thomas, Rothbart
      and Kagan), which derived their temperament concept from early childhood
      observations. Recent theories (e. g. those of Cloninger or Akiskal) combine
      different aspects. After reviewing the historical temperament concepts we present
      underlying factors which are linked to affective disorders (such as emotional
      reactivity, cyclicity or trait affectivity). Finally, we illustrate the
      importance of temperament concepts for research in affective disorders.

PMID- 12796853
TI  - Fabry disease: novel alpha-galactosidase A 3'-terminal mutations result in
      multiple transcripts due to aberrant 3'-end formation.
AB  - Mutations in the gene that encodes the lysosomal exoglycohydrolase, alpha
      galactosidase A (alpha-GalA), cause Fabry disease, an X-linked recessive inborn
      error of glycosphingolipid catabolism. Human alpha-GalA is one of the rare
      mammalian genes that has its polyadenylation signal in the coding sequence and
      lacks a 3' untranslated region (UTR). We identified two novel frameshift
      mutations, 1277delAA (del2) and 1284delACTT (del4), in unrelated men with
      classical Fabry disease. Both mutations occurred in the 3' terminus of the coding
      region and obliterated the termination codon, and del2 also altered the
      polyadenylation signal. To characterize these mutations, 3' rapid amplification
      of cDNA ends (RACE) and polymerase chain reactions (PCR) were performed, and the
      amplicons were subcloned and sequenced. Both mutations generated multiple
      transcripts with various lengths of 3' terminal sequences, some elongating
      approximately 1 kb. Mutant transcripts were classified as follows: type I
      transcripts had terminal in-frame thymidines that created termination codons when
      polyadenylated, type II had downstream termination codons within the elongated
      alpha-GalA sequence, and type III, the most abundant, lacked termination codons
      at their 3' ends. To determine if the type III transcripts were degraded by the
      recently described cytosolic messenger RNA degradation pathway for messages
      lacking termination codons, northern blot analysis was performed. However, the
      finding of similar levels of nuclear and cytoplasmic alpha-GalA mRNA in normal
      and patient lymphoblasts suggested that mRNA degradation did not result from
      either mutation. Expression of representative transcript types revealed
      differences in intracellular localization and/or protein stability and catalytic
      activity, with most mutant proteins being nonfunctional. Characterization of
      these 3' mutations identified a novel molecular mechanism causing classical Fabry
      disease.

PMID- 12796854
TI  - Mutational mechanisms of Williams-Beuren syndrome deletions.
AB  - Williams-Beuren syndrome (WBS) is a segmental aneusomy syndrome that results from
      a heterozygous deletion of contiguous genes at 7q11.23. Three large region
      specific low-copy repeat elements (LCRs), composed of different blocks (A, B, and
      C), flank the WBS deletion interval and are thought to predispose to misalignment
      and unequal crossing-over, causing the deletions. In this study, we have
      determined the exact deletion size and LCR copy number in 74 patients with WBS,
      as well as precisely defined deletion breakpoints in 30 of them, using LCR
      specific nucleotide differences. Most patients (95%) exhibit a 1.55-Mb deletion
      caused by recombination between centromeric and medial block B copies, which
      share approximately 99.6% sequence identity along 105-143 kb. In these cases,
      deletion breakpoints were mapped at several sites within the recombinant block B,
      with a cluster (>27%) occurring at a 12 kb region within the GTF2I/GTF2IP1 gene.
      Almost one-third (28%) of the transmitting progenitors were found to be
      heterozygous for an inversion between centromeric and telomeric LCRs. All
      deletion breakpoints in the patients with the inversion occurred in the distal 38
      kb block B region only present in the telomeric and medial copies. Finally, only
      four patients (5%) displayed a larger deletion ( approximately 1.84 Mb) caused by
      recombination between centromeric and medial block A copies. We propose models
      for the specific pairing and precise aberrant recombination leading to each of
      the different germline rearrangements that occur in this region, including
      inversions and deletions associated with WBS. Chromosomal instability at 7q11.23
      is directly related to the genomic structure of the region.

PMID- 12796857
TI  - Youth characteristics and contextual variables influencing physical activity in
      young adolescents of parents with premature coronary heart disease.
AB  - This study examined influences on physical activity of young adolescents whose
      parents have premature coronary heart disease (CHD). Consistent with
      Bronfenbrenner's theory, the influences examined were personal characteristics of
      the subjects and selected contextual variables (peers, family, and community).
      Subjects were 113 youths, aged 11 to 14, 53% boys, 73% Caucasian, all with
      parents with premature CHD. Children were most likely to be active if their
      fathers were active, and those living in the coastal region were less likely to
      be active than other children. Peer influence interacted with both pubertal
      status and geographic region in its effect on children's activity. Children were
      more active when they had active peers only when the youth were midpubertal or
      when they were in the coastal region. Results emphasize the importance of nursing
      interventions to influence behaviors of these vulnerable children.

PMID- 12796855
TI  - Selection of genetic markers for association analyses, using linkage
      disequilibrium and haplotypes.
AB  - The genotyping of closely spaced single-nucleotide polymorphism (SNP) markers
      frequently yields highly correlated data, owing to extensive linkage
      disequilibrium (LD) between markers. The extent of LD varies widely across the
      genome and drives the number of frequent haplotypes observed in small regions.
      Several studies have illustrated the possibility that LD or haplotype data could
      be used to select a subset of SNPs that optimize the information retained in a
      genomic region while reducing the genotyping effort and simplifying the analysis.
      We propose a method based on the spectral decomposition of the matrices of
      pairwise LD between markers, and we select markers on the basis of their
      contributions to the total genetic variation. We also modify Clayton's "haplotype
      tagging SNP" selection method, which utilizes haplotype information. For both
      methods, we propose sliding window-based algorithms that allow the methods to be
      applied to large chromosomal regions. Our procedures require genotype information
      about a small number of individuals for an initial set of SNPs and selection of
      an optimum subset of SNPs that could be efficiently genotyped on larger numbers
      of samples while retaining most of the genetic variation in samples. We identify
      suitable parameter combinations for the procedures, and we show that a sample
      size of 50-100 individuals achieves consistent results in studies of simulated
      data sets in linkage equilibrium and LD. When applied to experimental data sets,
      both procedures were similarly effective at reducing the genotyping requirement
      while maintaining the genetic information content throughout the regions. We also
      show that haplotype-association results that Hosking et al. obtained near CYP2D6
      were almost identical before and after marker selection.

PMID- 12796858
TI  - The effect of music-reinforced nonnutritive sucking on feeding rate of premature
      infants.
AB  - Premature infants are fed by gavage tube before 34 weeks adjusted gestational age
      and when nipple feeding results in detrimental changes in respiration and heart
      rate. Nipple feeding skill must be developed and correlates with length of
      hospitalization and neurobehavioral development. This study provided music
      reinforcement for nonnutritive sucking and assessed nipple feeding rates pre- and
      posttreatment for 32 infants referred as poor feeders. A pacifier fitted with a
      pressure transducer activated 10 seconds of recorded music in a one-trial, 15
      minute intervention given to experimental infants (n = 16) 30 to 60 minutes
      before the late afternoon bottle feeding. Feeding rates were collected for bottle
      feedings pre- and postintervention and for a similar interval for a no-contact
      control group (n = 16). Results showed that the intervention significantly
      increased feeding rates. Music functioned as reinforcement and the sucking
      behavior transferred from a nonnutritive to a nutritive event.

PMID- 12796859
TI  - Munchausen syndrome by proxy: identification and diagnosis.
AB  - Child abuse claims the lives of three children daily in the United States;
      however, one form of child abuse frequently goes undiagnosed-the true incidence
      is not known. Munchausen Syndrome by Proxy (MSBP) is a hidden and deceitful abuse
      whereby a caretaker of a child, usually the mother, fabricates information
      concerning the child's health or intentionally makes the child ill for personal
      attention and psychologic gain. Because health care professionals are the child's
      first line of defense against MSBP, they must know all about the disorder to be
      able to identify MSBP and protect children from disability or death.

PMID- 12796860
TI  - The demands of biochemical genetic disorders: a survey of mothers of children
      with mitochondrial disease or phenylketonuria.
AB  - A telephone survey of mothers of children with mitochondrial disease (n = 29) or
      phenylketonuria (PKU) (n = 29) revealed that mothers of children with
      mitochondrial disease report greater stress and worry, less satisfaction with
      social supports, greater difficulty meeting their child's extra care needs, and
      more impact on multiple aspects of their personal lives. They also reported more
      missed days of work and used a greater number of health care services and
      personal resources. Interventions must be developed that address the demands of
      biochemical genetic disorders, particularly those with the uncertain trajectory
      of mitochondrial disease.

PMID- 12796861
TI  - The relationship between health risk behaviors and fear in one urban seventh
      grade class.
AB  - A descriptive, correlational study was undertaken with 54 urban, 7th graders
      (age, 11-13 y) from one class. By using the Youth Risk Behaviors Surveillance
      System Questionnaire (YRBSS), information was collected about health risk
      behaviors as well as unintentional and intentional injury. Findings indicate that
      these adolescent students have significant fears related to their environment;
      they are fearful of being hurt. These students also reported increased incidence
      of health risk behaviors including alcohol use, carrying weapons, and staying up
      late at night. The findings suggest a need to understand how adolescents channel
      fear of harm to self into other unhealthy behaviors. Nurses are often in an ideal
      position to assess the health and behaviors of adolescents and to offer
      education, health promotion, and support to this at-risk population.

PMID- 12796862
TI  - Stressors and stress symptoms of mothers with children in the PICU.
AB  - The purpose of this study was a description of sources of stress and stress
      symptoms over time for mothers with a child in the pediatric intensive care unit
      (PICU) and a comparison with mothers with a child in a general care unit (GCU).
      The sample contained 31 PICU mothers and 32 GCU mothers who were studied during
      four time periods over 6 months using the Parental Stressor Scale: PICU and the
      Symptom Checklist-90-Revised. Findings showed all the PICU mothers were stressed
      from the total intensive care experience and the use of monitors. PICU mothers
      experienced more stress symptoms than the GCU mothers did during all four time
      periods. This is valuable information because nurses should know how mothers of
      critically ill children feel and what stresses them in order to help the mothers
      and teach them about what changes to expect in themselves. Nursing practice must
      enable parents to continue in their family roles to be effective and therapeutic
      to their children.

PMID- 12796863
TI  - The President's New Freedom Commission on Mental Health: significance for
      children.

PMID- 12796864
TI  - Children and video games.

PMID- 12796865
TI  - The world of the child: a world of play even in the hospital.
AB  - Play is an integral part of a child's life. Working with children in the hospital
      is based on the worldly view that claims that the patient is first and foremost a
      child. Investing in his mental well-being will assist him and his parents to
      better cope with his illness and hospitalization. From this point of view, many
      activities have been developed at Schneider Children's Medical Center of Israel
      (SCMCI), where the focus is on play. It is vital that the nurses work in
      cooperation with the educational staff and also integrate components of play
      during routine activity, in preparing children for surgeries and invasive
      procedures, and during painful or uncomfortable interventions.

PMID- 12796866
TI  - An evidence-based pilot study exploring relationships between psychologic and
      physiologic factors in post-lung-transplant adolescents with cystic fibrosis.
AB  - After using an evidence-based approach to address clinical practice questions, a
      pilot study was designed to explore the relationships among anxiety and
      depression self-report data, cyclosporine (CSA) trough values, and biopsy
      rejection grades within a posttransplant sample of adolescents with cystic
      fibrosis. Thirteen study participants completed the Revised Children's Manifest
      Anxiety Scale (RCMAS) and the Children's Depression Inventory (CDI), and had CSA
      trough levels and biopsy data collected. There was a statistically significant
      correlation between depression and inflammatory rejection levels. Adolescents
      with benign rejection scores had lower depression scores than adolescents with
      higher levels of rejection scores. The data also showed a statistically
      significant inverse correlation between CSA trough levels and inflammatory
      rejection levels. Posttransplant success depends on compliance with a strict,
      antirejection regimen. Adolescence is a turbulent time when many stressors can
      result in risk-taking behavior such as medication noncompliance and anxiety and
      depression. Regular psychologic monitoring of posttransplant adolescent patients
      may be warranted to identify increasing psychologic distress and proactive
      opportunities for health care intervention. This pilot study is an example of a
      clinical research question that evolved from a practice situation in which nurses
      caring for posttransplant adolescents with cystic fibrosis surmised that there
      were many psychologic issues influencing successful transplant outcomes. Nursing
      observations suggested a strong connection between poorer medication control,
      greater risk for rejection, and signs of depression and/or anxiety. The nurse
      researchers were interested in identifying significant relationships between
      psychologic factors and physiologic factors, and in discovering objective ways to
      better assess the psychologic needs of this patient population. A thorough search
      was conducted of the research literature, and the best clinical practices of
      other institutions were investigated. There was a lack of transplant research
      literature on adolescents, and although excellent ideas were generated from
      inquiries to other institutions, there was a lack of best evidence to answer the
      clinical questions about this group of patients. The initial clinical question
      became a research question to determine more about this specific patient
      population. This article is an example of a clinical research pilot study that
      resulted from an evidence-based practice process. Pilot studies are springboards
      for other, more refined research: They help to point the way, or to clarify what
      the real issues may be. For nurses, they serve as an opportunity to hone critical
      thinking skills and to contribute to the scientific foundation of our profession.

PMID- 12796867
TI  - Those who keep us free.

PMID- 12796868
TI  - Calcitonin therapy for central giant cell granuloma.
AB  - PURPOSE: A number of alternative nonsurgical therapies have been advocated in
      recent years for the management of the central giant cell granuloma (CGCG). These
      include calcitonin injections, intralesional steroid injections and subcutaneous
      alpha-interferon injections. This report provides the results of calcitonin
      therapy. MATERIALS AND METHODS: Ten patients received calcitonin therapy, 9 via
      subcutaneous injection and 1 via nasal spray, for the management of a CGCG.
      Patients were reviewed retrospectively RESULTS: In 8 cases, the lesions resolved
      completely after 19 to 21 months of subcutaneous calcitonin treatment. In the
      ninth case, the lesion resolved on calcitonin treatment only to reappear 26
      months later. The recurrence was treated with both repeated calcitonin and local
      enucleation. The tenth case with calcitonin (intranasal) treatment was abandoned
      due to poor patient compliance, and the patient ultimately underwent surgical
      treatment. CONCLUSION: Calcitonin treatment appears to be a viable option for the
      treatment of CGCGs but, because of the length of treatment time, should probably
      be reserved for multiple lesions, recurrent lesions, or particularly aggressive
      lesions. The exact mechanism of action of both calcitonin and other treatment
      modalities remains to be fully elucidated. The reported success of all such
      treatments raises questions about the natural history of this lesion.

PMID- 12796870
TI  - Changes in temporomandibular joint dysfunction after orthognathic surgery.
AB  - PURPOSE: We sought to evaluate the effects of orthognathic surgery on
      temporomandibular joint (TMJ) dysfunction in patients with known presurgical TMJ
      internal derangement who underwent double-jaw surgery for the treatment of
      dentofacial deformities. PATIENTS AND METHODS: Treatment records of 25 patients
      with magnetic resonance imaging and clinical verification of preoperative TMJ
      articular disc displacement who underwent double-jaw surgery only were
      retrospectively evaluated, with an average follow-up of 2.2 years. Signs and
      symptoms of TMJ dysfunction, including pain, range of mandibular motion, and
      presence/absence of TMJ sounds, were subjectively (visual analog scales) and
      objectively evaluated at presurgery (T1), immediately postsurgery (T2), and at
      longest follow-up (T3). Surgical change (T2-T1) and long-term stability of
      results (T3-T2) were calculated using the superimposition of lateral
      cephalometric and tomographic tracings. RESULTS: Presurgery, 16% of the patients
      had only TMJ pain, 64% had only TMJ sounds, and 20% had both TMJ pain and sounds.
      Postsurgery, 24% of the patients had only TMJ pain, 16% had only TMJ sounds, and
      60% has both TMJ pain and sounds. Thus, presurgery 36% of the patients had TMJ
      pain, and postsurgery, 84% had pain. Average visual analog scale pain scores were
      significantly higher postsurgery and none of the patients with presurgery TMJ
      pain had relief of pain postsurgery. In addition, 6 patients (24%) developed
      condylar resorption postsurgically, resulting in the development of Class II open
      bite malocclusion. CONCLUSIONS: Patients with preexisting TMJ dysfunction
      undergoing orthognathic surgery, particularly mandibular advancement, are likely
      to have significant worsening of the TMJ dysfunction postsurgery. TMJ dysfunction
      must be closely evaluated, treated if necessary, and monitored in the
      orthognathic surgery patient.

PMID- 12796872
TI  - Oral and maxillofacial surgery in patients with chronic orofacial pain.
AB  - PURPOSE: In this investigation, we evaluated a population of patients with
      chronic orofacial pain who sought treatment at a pain center in an academic
      institution. These patients were evaluated with respect to 1) the frequency and
      types of previous oral and maxillofacial surgery procedures, 2) the frequency of
      previous significant misdiagnoses, and 3) the number of patients who subsequently
      required surgical treatment as recommended by an interdisciplinary orofacial pain
      team. The major goal of this investigation was to determine the role of oral and
      maxillofacial surgery in patients with chronic orofacial pain. PATIENTS AND
      METHODS: The study population included patients seen at the Center for Oral,
      Facial and Head Pain at New York Presbyterian Hospital from January 1999 through
      April 2001. (120 patients; female-to-male ratio, 3:1; mean age, 49 years; average
      pain duration, 81 months; average number of previous specialists, 6). The patient
      population was evaluated by an interdisciplinary orofacial pain team and the
      following characteristics of this population were profiled: 1) the frequency and
      types of previous surgical procedures, 2) diagnoses, 3) the frequency of previous
      misdiagnoses, and 4) treatment recommendations made by the center team. RESULTS:
      There was a history of previous oral and maxillofacial surgical procedures in 38
      of 120 patients (32%). Procedures performed before our evaluation included
      endodontics (30%), extractions (27%), apicoectomies (12%), temporomandibular
      joint (TMJ) surgery (6%), neurolysis (5%), orthognathic surgery (3%), and
      debridement of bone cavities (2%). Surgical intervention clearly exacerbated pain
      in 21 of 38 patients (55%) who had undergone surgery. Diagnoses included
      myofascial pain (50%), atypical facial neuralgia (40%), depression (30%), TMJ
      synovitis (14%), TMJ osteoarthritis (12%), trigeminal neuralgia (10%), and TMJ
      fibrosis (2%). Treatment recommendations included medications (91%), physical
      therapy (36%), psychiatric management (30%), trigger injections (15%), oral
      appliances (13%), biofeedback (13%), acupuncture (8%), surgery (4%), and Botox
      injections (1%) (Allergan Inc, Irvine, CA). Gross misdiagnosis leading to serious
      sequelae, with delay of necessary treatment, occurred in 6 of 120 patients (5%).
      CONCLUSIONS: Misdiagnosis and multiple failed treatments were common in these
      patients with chronic orofacial pain. These patients often have multiple
      diagnoses, requiring management by multiple disciplines. Surgery, when indicated,
      must be based on a specific diagnosis that is amenable to surgical therapy.
      However, surgical treatment was rarely indicated as a treatment for pain relief
      in these patients with chronic orofacial pain, and it exacerbated and perpetuated
      pain symptoms in some of them.

PMID- 12796873
TI  - A comparative study of 2 imaging techniques for the diagnosis of condylar
      fractures in children.
AB  - PURPOSE: We sought to compare the sensitivity and specificity of panoramic
      radiographs with those of coronal computed tomography (CT) scans in the diagnosis
      of mandibular condylar fractures in the pediatric population. METHODS: Medical,
      dental, and radiographic records of patients who presented between 1995 and 2000
      were evaluated for injuries involving the mandibular condyle. The sample included
      22 males and 15 females with ages ranging from 2 to 15 years (mean, 8 years).
      Control subjects were added and matched by age and gender. The panoramic
      radiographs were blocked to allow separate evaluation of each condyle.
      Representative images from the CT scans were selected and individually
      photographed for projection. Both sets of images were evaluated by 4 groups of
      examiners: oral and maxillofacial (OMF) surgeons who regularly deal with
      pediatric trauma (n = 2), community OMF surgeons who had been out of training for
      at least 5 years (n = 6), OMF radiologists (n = 3), and OMF surgery residents (n
      = 6). Each image was shown for 20 seconds and the examiners were given 3 options
      to choose: 1) fracture, 2) no fracture, and 3) uncertain. RESULTS: The overall
      diagnostic accuracy of CT scanning was 90% (sensitivity, 92%; specificity, 87%),
      and that of panoramic radiographs was 73% (sensitivity, 70%; specificity, 77%).
      Of interest, the most experienced clinicians were also those most likely to
      respond that panoramic films were not diagnostic. Statistical analysis of the
      results was performed using chi(2) analysis. The differences for sensitivity
      measurements using the CT scan were not statistically significant (P >.1).
      However, the differences in sensitivity measurements using the panoramic
      radiographs and the specificity measurements using both the CT and panoramic
      radiographs were statistically significant (P <.05). CONCLUSIONS: CT scans
      provide consistently greater accuracy of diagnosis, sensitivity, and specificity
      than panoramic radiographs in the assessment of children suspected of having
      condylar fractures. In view of the high rate of false-negative and false-positive
      results associated with panoramic radiographs, coronal CT scans should be
      considered routine investigation in these patients.

PMID- 12796875
TI  - Oral malignancies associated with negative transepithelial brush biopsy.
AB  - PURPOSE: This study was performed to assess the incidence of negative brush
      biopsy for oral lesions later demonstrated histologically to be squamous cell
      carcinoma. METHODS: All diagnoses of oral squamous cell carcinoma from a
      university oral pathology service for the period June 2000 through March 2002
      were reviewed to determine if any had previously undergone brush biopsy reported
      to be "negative for epithelial abnormality." Those cases identified were further
      investigated to determine the time lapse between brush biopsy and definitive
      tissue diagnosis. RESULTS: Four cases of brush biopsy negative squamous cell
      carcinoma were identified from 115 total cases of malignancy (3.5%). The average
      time from brush biopsy to tissue diagnosis was 117.25 days (range, 5 to 292
      days). CONCLUSION: False negative reports are possible with the oral brush biopsy
      technique. Persistent lesions should undergo tissue biopsy for definitive
      diagnosis.

PMID- 12796876
TI  - Dedifferentiation of odontogenic keratocyst epithelium after cyst decompression.
AB  - PURPOSE: Cytokeratin-10 expression by cystic epithelium has been shown in the
      suprabasilar layers of odontogenic keratocyts (OKCs) but not in dentigerous
      cysts. Cyst decompression and irrigation result in the loss of keratinization. In
      this study, we used cytokeratin-10 antibody staining to evaluate changes in OKC
      epithelium to determine if decompression/irrigation treatment results in an
      epithelial modulation that may be associated with lower long-term recurrence.
      METHODS: Fourteen OKCs were exteriorized by removal of mucosa and bone. An
      irrigation port was placed into the cyst for twice-daily irrigations. At 3-month
      intervals, panoramic radiographs were obtained and cyst-lining cells were sampled
      and stained for cytokeratin-10. Residual cystectomy was performed when necessary
      based on clinical and radiographic criteria, and the lining was evaluated by
      histologic and immunohistochemical examination. RESULTS: There were 6 males and 8
      females with a mean age of 32 years. Ten cysts were mandibular, and 4 were
      maxillary. Average duration of irrigation was 8.4 months (range, 6 to 12 months),
      and the mean shrinkage of the radiolucency was 65% (range, 5% to 91%). All
      cytologic samples obtained at 3 and 6 months contained cytokeratin-10-positive
      epithelial cells. At the time of cystectomy, 9 of 14 cases were cytokeratin-10
      negative and no longer showed histologic features of OKCs. Specimens from the
      remaining 5 patients were histologically consistent with OKC and were cytokeratin
      10 positive. Mean treatment time of the cytokeratin-10-positive group was 7
      months, and that of the cytokeratin-10-negative group was 9 months. CONCLUSION:
      Epithelial dedifferentiation and loss of cytokeratin-10 production were observed
      in 64% of patients treated by cyst decompression/irrigation after a 9-month
      average treatment time. Longitudinal follow-up of these patients will determine
      whether this change is associated with lower rates of recurrence than alternative
      OKC therapy.

PMID- 12796878
TI  - Comparison of 2 temporomandibular joint total joint prosthesis systems.
AB  - PURPOSE: The study goal was to evaluate the comparative outcomes of patients
      treated with temporomandibular joint (TMJ) total joint prostheses, using either
      the Christensen prosthesis (TMJ Inc, Golden, CO) (CP) or the TMJ Concepts
      prosthesis (TMJ Concepts Inc, Camarillo, CA; formerly Techmedica Inc) (TP).
      PATIENTS AND METHODS: Forty-five consecutive patients treated with either CP or
      TP total joint prostheses were evaluated. The CP group consisted of 23 patients
      (40 prostheses; average patient age, 38.8 years). The TP group consisted of 22
      patients (38 prostheses; average patient age, 38.5 years). The average number of
      previous operations for the CP group was 3.9, whereas it was 2.6 for the TP
      group. The CP and TP groups had an average follow-up of 20.8 and 33.0 months,
      respectively. Patients were evaluated for incisal opening and occlusal and
      skeletal stability. A visual analog scale was used for subjective assessment of
      TMJ pain (0 = no pain, 10 = worst pain), jaw function (0 = normal function, 10 =
      no function), and diet (0 = no limitations, 10 = liquids only). Statistical
      analysis was performed using an independent t test, and a value of P <.05 was
      considered significant. RESULTS: The average postsurgical incisal opening for the
      CP group was 30.1 mm (increase of 6.7 mm), and that for the TP group was 37.3 mm
      (increase of 9.9 mm), indicating significant increase of the TP group (P =.008).
      The average postsurgical pain level for the CP group was 6.0, a decrease of 1.8,
      and that for the TP group was 4.1, a decrease of 3.1, indicating significant
      improvement for the TP group (P =.042). Postsurgical average jaw function for CP
      was 5.5, an improvement of 1.2. The postsurgical TP average was 3.9, an
      improvement of 3.0, showing significant improvement for the TP group (P =.008).
      Average postsurgical diet rating for the CP group was 5.4, an improvement of 1.8.
      The TP group average was 3.9, an improvement of 2.0, indicating significant
      improved eating ability for the TP group (P =.021). Skeletal and occlusal
      stability were good in both groups. CONCLUSION: The TP group had statistically
      significant improved outcomes compared with the CP group relative to postsurgical
      incisal opening, pain, jaw function, and diet. Both groups showed good skeletal
      and occlusal stability.

PMID- 12796880
TI  - Survival rate of IMZ implants: a prospective 10-year analysis.
AB  - PURPOSE: The purpose of this study was to determine the success of IMZ implants
      after prosthodontic rehabilitation. PATIENTS AND METHODS: A prospective study
      analysis was made of the treatment results for 541 patients after the insertion
      of a total of 1,250 IMZ implants at 2 practicing dentists' offices over a period
      of 13 years. The most frequent treatment situations were insertion in the totally
      edentulous lower jaw (44.1%) and in a distal edentulous region (37.6%). The
      statistical survival rate assessment was made using Kaplan-Meier survival
      analysis. The results were compared with the cumulative survival rates for all
      implants during a period of 10 years. RESULTS: At 5 years after insertion, 96.0%
      of all implants were in situ and noninflamed; after 10 years, the survival rate
      was 82.4%. For both the upper and the lower jaw, better results were recorded in
      the posterior part of the jaw than in the anterior part. CONCLUSIONS: The IMZ
      implant system showed a good 10-year-survival rate.

PMID- 12796881
TI  - A cervical lymph node metastatic model of human tongue carcinoma: Serial and
      orthotopic transplantation of histologically intact patient specimens in nude
      mice.
AB  - PURPOSE: A lymph node metastatic model of human tongue carcinoma using orthotopic
      and serial transplantation was established in nude mice to study the invasive and
      metastatic properties of human tongue cancer. MATERIALS AND METHODS: Lymph node
      metastatic specimens of human tongue carcinoma were transplanted into nude mice
      orthotopically. Tumors dissected from the metastatic lymph nodes of the nude mice
      were serially transplanted into tongues of disease-free nude mice at 4-week
      intervals. RESULTS: All mice developed aggressive and diffuse well-differentiated
      squamous cell carcinoma at tongue recipient sites. Tumor cells invaded to
      lymphatic vessels. In addition, increased cervical lymph node metastasis was
      noted in the first (3 of 14, or 21%), second (4 of 11, or 36%), third (6 of 10,
      or 60%), or fourth (11 of 14, or 79%) transplantation. In mice, 2 of 14 lung
      metastases were found in the fourth round of transplantation. CONCLUSION: After
      surgical specimens of the lymph node metastasis for human tongue cancer were
      transplanted into the tongue of nude mice, the clinical characteristics of human
      tongue carcinoma, especially invasion and metastasis, were observed. This
      metastatic model involving orthotopic and serial transplantation should be useful
      for studies on the mechanisms, treatment, and prevention of human carcinoma of
      tongue.

PMID- 12796882
TI  - Is there a correlation between performance on dental and medical board
      examinations?
AB  - PURPOSE: The purpose of this study was to determine whether a correlation exists
      between passing the United States Medical Licensing Examination (USMLE) Step 1
      (USMLE) on the first attempt and performance on National Board Dental Examination
      Part I (NBDE). MATERIALS AND METHODS: Questionnaires were sent to program
      directors of 52 dual-degree oral and maxillofacial surgery programs. The
      information requested concerned residents of each program from 1990 to 2000 and
      included NBDE scores and number of attempts each resident took to pass the USMLE
      Step 1. Also included was the number of years of medical school each program
      required, as well as time given to USMLE Step 1 study preparation. The data were
      analyzed to determine if a relationship exists between NBDE Part I score and pass
      rate on the USMLE Step 1 on the first attempt. Data presented are the mean +/-
      SD. RESULTS: Questionnaires were received from 26 of 52 (50%) dual-degree oral
      and maxillofacial surgery programs regarding 426 residents. The overall average
      of NBDE Part 1 was 92.55 +/- 3.62 (range, 83 to 99). The average NBDE Part I
      score for those candidates who passed the USMLE Step 1 on the first attempt was
      93.75 +/- 3.02, and for those who did not pass the USMLE Step 1 on the first
      attempt, it was 89.12 +/- 2.93. The average NBDE Part I score is significantly
      higher for those subjects who passed the USMLE Step 1 on the first attempt (P
      <.001). A candidate with an NBDE Part I score of 95 to 99 is 75 times more likely
      to pass the USMLE Step 1 on the first attempt than is a candidate with a score of
      less than 90. A marginal association was found with study preparation time and
      amount of medical school completed during residency. CONCLUSIONS: A significant
      correlation exists between NBDE Part I score and pass rate on the USMLE Step 1
      examination.

PMID- 12796883
TI  - The effects of mechanical strain on synovial fibroblasts.
AB  - PURPOSE: Arthritic diseases of the temporomandibular joint, such as rheumatoid
      arthritis and osteoarthritis, suggest that inflammatory mediators and
      metalloproteinases may play a role in their pathogenesis. Recent clinical
      evidence from physical therapy and other modalities has shown a significant
      decrease in temporomandibular joint symptoms in patients with early disease. This
      project examines the effect of mechanical strain on synovial fibroblasts'
      production of inflammatory mediators including prostaglandin E(2) (PGE(2)) and
      proteinases. MATERIALS AND METHODS: An established synovial fibroblast cell line
      (HIG-82) was grown to confluency in modified Eagle's medium supplemented with 10%
      fetal calf serum. The monolayer of fibroblasts was then subjected to mechanical
      strain using the Flexercell Strain Unit (Flexcell International Corporation,
      McKeesport, PA) at 3 cycles per minute, with 10 seconds' elongation of up to 24%
      and 10 seconds of relaxation. Levels of PGE(2) were determined by
      radioimmunoassay using commercially available product and measured in nanograms
      per milliliter of supernatant. Proteinases collagenase, gelatinase, and
      stromelysin were measured by H(3) radioactive labeling of acidic anhydride to the
      specific substrate. Enzymatic proteolysis of the radiolabeled substrate was then
      measured in supernate as units per milliliter. Statistical analysis of all
      results was performed using Student's t test in triplicate. RESULTS: PGE(2)
      levels of mechanically activated cells was 18.1 +/- 13.4 ng/mL, with control
      levels being 58.0 +/- 9.2 ng/mL. This is a statistically significant decrease,
      between strained and unstrained cells with P <.05. In control cells, proteinase
      activity that degrades collagen, gelatin, or casein was 4.27 +/- 1.5, 4.62 +/-
      0.11, or 0.11 +/- 0.01 U/mL, respectively. Levels for mechanically strained cells
      were 3.99 +/- 1.90, 4.02 +/- 0.90, and 0.12 +/- 0.01 U/mL, respectively. These
      results show that there is a significant decrease in PGE(2) levels of synovial
      fibroblasts undergoing mechanical strain. Proteinases examined show no difference
      in levels between mechanically activated fibroblasts and their controls.
      CONCLUSION: This decrease in PGE(2) production in synovial fibroblasts could help
      elucidate the mechanism by which physical therapy, and in particular continuous
      passive motion, may decrease inflammatory mediators of the temporomandibular
      joint.

PMID- 12796884
TI  - Pattern of mandibular fractures in an urban major trauma center.
AB  - PURPOSE: Many studies focusing on the pattern of presentation of mandibular
      fractures are inconclusive. This is largely due to a multifactorial involvement
      of associated factors and the role of anatomic factors. PATIENTS AND METHODS: We
      reviewed a 10-year retrospective analysis of the pattern of presentation of
      mandibular fractures at an urban level I trauma center in Washington, DC, and the
      significance of the variables in association with the fractures. These include
      mechanism of action, age group, illicit drug use, seasonal variation, and the
      incidence of multiple fracture sites. We also looked at the evolving pattern of
      mandibular fractures in comparison to an earlier study conducted in the 1960s at
      the same hospital. Data collection was done through the use of medical records
      and all documented radiographs. Variables that were analyzed in association with
      the fractures include age, gender, mechanism of action, seasonal variation, and
      anatomic location. Data analysis was done using subjective analysis, frequency
      distribution, and multiple regression tests, where appropriate. RESULTS: Data
      analysis shows that 86% of all fracture patients are male, and 37% of all
      patients were in the 25- to 34-year-old age group. Use of an illicit substance at
      the time of trauma was seen in 55% of all cases. Interpersonal violence accounted
      for 79% of all patients, with prevalence in the summer (31%) and winter (28%)
      months. The most common location of fracture is in the angle region (36%),
      followed by the body (21%) and parasympyhseal region (17%), with 52% presenting
      with more than one fracture site. CONCLUSION: The evolving pattern of fractures
      in urban trauma centers is showing an increasing trend of association with
      illicit substances and interpersonal violence as a major causative factor.

PMID- 12796885
TI  - Brown tumor of the maxilla and mandible: progressive mandibular brown tumor after
      removal of parathyroid adenoma.

PMID- 12796886
TI  - Microcystic adnexal carcinoma: report of a case.

PMID- 12796887
TI  - Intraneural epithelial islands associated with a periapical granuloma: a cause
      for concern?

PMID- 12796888
TI  - Interesting eruption of 4 teeth associated with a large dentigerous cyst in
      mandible by only marsupialization.

PMID- 12796889
TI  - Case report: myocardial metastasis of a maxillary malignant ameloblastoma.

PMID- 12796890
TI  - Odontogenic myxoma in a 17-month-old child: a case report.

PMID- 12796892
TI  - Who should be performing fetal ultrasound?

PMID- 12796891
TI  - Meta-analysis of surgical treatments for temporomandibular articular disorders: a
      reply to the discussants.

PMID- 12796893
TI  - The value of performing a dating scan on all women in antenatal screening for
      Down's syndrome and neural tube defects.

PMID- 12796894
TI  - Routine ultrasonography in utero and subsequent growth during childhood.
AB  - The study was performed to investigate any associations between routine
      ultrasonography during pregnancy and subsequent growth during childhood. A follow
      up was carried out of children born to women who took part in two randomized,
      controlled trials of ultrasonic screening during pregnancy. From a total of 2428
      eligible children, 2140 (88%) were followed up with measurements of growth at
      Norwegian maternal and child health centers. The body weight and height were
      recorded at birth and at 3, 6 and 12 months of age; and subsequently at 2, 4 and
      7 years of age. A repeated-measures analysis of growth was carried out,
      stratified by maternal smoking in a subsample of 1201 children. No significant
      differences between ultrasound-screened children, and their controls, were found
      in mean body weight, or height, at birth and at all the subsequent visits to the
      health centers. However, the repeated-measures analysis of variance in the
      subsample indicated that growth from birth to 7 years of age differed
      significantly (p = 0.02) between screened and control children of mothers who
      reported smoking at the first antenatal visit. We conclude that children who were
      routinely exposed to ultrasonography in utero showed no statistically significant
      differences in growth during childhood compared to control children.

PMID- 12796895
TI  - Evaluation of biophysical fetal assessment in high-risk pregnancy to assess
      ultrasound parameters suitable for screening in the low-risk population.
AB  - During a 1-year period, 662 pregnant women at 24-43 weeks' gestation were
      referred to the Department of Obstetrics and Gynaecology, at the Queens
      University Belfast, for fetal assessment because they were clinically suspected
      to be at high risk of perinatal complications. The results of our investigations
      were made available to the referring obstetricians who undertook the further
      management of the pregnancies. Subsequently six pregnancies resulted in perinatal
      deaths and 97 (14.7%) in the delivery of small-for-gestational-age infants. We
      restrospectively analyzed the data from ultrasonographic evaluation of the fetus
      and subjective and objective assessments of the amniotic fluid volume to
      determine their value in the prediction of adverse perinatal outcome. A fetal
      abdominal circumference < 10th centile for gestation or a subjectively reduced
      amniotic fluid volume identified 87 (90%) of small-for-gestational-age infants
      and five of the six perinatal deaths. When comparing the abdominal circumference
      and subjective liquor volume, both were sensitive in predicting delivery of a
      small-for-gestational-age fetus (sensitivity 86% vs. 53%, respectively) and
      perinatal death (sensitivity 50% vs. 83%, respectively). We suggest that, since
      assessments of these two factors are complementary in evaluating a high-risk
      pregnancy and can be measured in under 5 min, they now warrant consideration for
      screening in a prospective randomized trial in an unselected low-risk population.

PMID- 12796896
TI  - Doppler velocimetry of the uterine artery as a screening test for gestational
      hypertension.
AB  - Doppler ultrasound was used to study the main uterine artery flow velocity
      waveforms in an unselected population of 272 primiparous women at 22 weeks'
      gestation. The incidences of subsequent complications were as follows:
      gestational hypertension alone, 4.4%; intrauterine fetal growth retardation
      alone, 4%; and gestational hypertension with intrauterine growth retardation,
      3.6%. The flow velocity waveform was considered abnormal when the resistance
      index in the uterine artery was greater than 0.58. This identified 9.5% of the
      population as 'at risk' and predicted either of the above outcomes with an
      overall sensitivity of 74% (kappa index, 0.72). The sensitivity of prediction for
      gestational hypertension alone was 50% while for proteinuric gestational
      hypertension it was 88%. The best result was obtained for the prediction of
      pregnancies affected by both gestational hypertension and intrauterine growth
      retardation, where the sensitivity was 100%.

PMID- 12796897
TI  - Sonographic dating of pregnancies conceived after contraceptive pill therapy.
AB  - A total of 358 women succeeded in conceiving in the first cycle after stopping
      oral contraception. The estimated day of delivery was calculated from both an
      ultrasonographically measured fetal biparietal diameter, in the second trimester,
      and from the date of the withdrawal bleed. According to the biparietal diameter
      measurement, the estimated day of delivery was postponed more than 1 week in 138
      cases (38.5%). For 304 women who delivered after the spontaneous onset of labor,
      the biparietal diameter estimate gave the best prediction of the day of delivery
      in 175 cases (57.6%), the date of the withdrawal bleed gave the best estimate in
      91 (29.9%) (p < 0.001) and they were equally good in 38 (12.5%). The estimated
      day of delivery using a biparietal diameter measurement was within +/- 14 days of
      the day of delivery for 267 of these 304 women (87.8%). The corresponding figure
      for the withdrawal bleed date was 218 (71.7%) (p </= 0.001). According to the
      withdrawal bleed date estimate, 68 women (22.4%) delivered beyond the estimated
      42 weeks, compared to only 2.6% according to the biparietal diameter estimate.
      The median length of a pregnancy from the first day of the withdrawal bleed was
      286 days and from the biparietal diameter was 281 days.

PMID- 12796898
TI  - Changes in inferior vena cava blood flow velocity and diameter during breathing
      movements in the human fetus.
AB  - Breathing movements in the human fetus cause distinct changes in Doppler flow
      velocity measurements at arterial, venous and cardiac levels. In adults,
      breathing movements result in a momentary inspiratory collapse of the inferior
      vena cava vessel wall. The study objective was to quantify the inferior vena cava
      flow velocity modulation during fetal breathing movements and to evaluate
      possible inferior vena cava vessel diameter changes in normal third-trimester
      pregnancies. We studied 57 women after oral administration of dextrose (50 g). In
      40 fetuses (n = 19, 27-32 weeks and n = 21, 36-39 weeks), fetal inferior vena
      cava waveforms were obtained during apnea and fetal breathing activity. In 30
      fetuses (27-39 weeks) inferior vena cava vessel diameter changes were studied
      using the M-mode during apnea and breathing movements. Peak and time-averaged
      velocities of inferior vena cava flow velocity waveforms showed a gestational age
      independent increase of 60-160% during breathing activity. A temporary inferior
      vena cava vessel wall collapse (range, 50-83%) was recorded, which was
      significantly different from vessel diameter changes during apnea (range, 11
      19%). The marked increase of inferior vena cava flow velocities is due to a
      raised thoraco-abdominal pressure gradient, which may cause a reduction in vessel
      size and additional volume flow into the right atrium. The significance of the
      caval index for recognition of elevated right atrial pressure in abnormal human
      fetal development needs further investigation.

PMID- 12796899
TI  - The minimum number of cardiac cycles necessary for calculation of renal blood
      flow velocity indices in pregnant and non-pregnant women.
AB  - In this study Doppler ultrasound was used to measure the blood flow velocity in
      the main and segmental renal arteries in 16 healthy non-pregnant women. There
      were no differences in blood flow indices between the right and left kidneys as
      well as between the main and segmental arteries. The variability of the indices
      in the main and segmental renal arteries in healthy non-pregnant and in the
      segmental renal artery in normal pregnant women (32-37 weeks of gestation) was
      investigated. The within-patient error standard deviations of ten cycles and two,
      and three to nine averaged cycles were compared. In non-pregnant women, values
      for the error standard deviation comparable with those obtained from ten cycles
      for the systolic/diastolic ratio and pulsatility index from both main and
      segmental arteries were obtained by averaging from five to six consecutive
      cycles, while the error standard deviation for the resistance index stabilized
      when averaging only two to four cycles. In pregnant women, the error standard
      deviations for both the systolic/diastolic ratio and pulsatility index reached
      quite stable values after three cycle had been averaged as did the error standard
      deviation for the resistance index. We speculate that this difference between non
      pregnant and pregnant women is due to more favorable conditions for renal
      visualization and consequently higher quality Doppler signals during pregnancy. A
      knowledge about the number of cardiac cycles required for an accurate calculation
      of renal blood flow velocity indices may prevent time-consuming calculations and
      inaccurate conclusions.

PMID- 12796900
TI  - Miscarriage diagnosis and gestational age estimation in the early first trimester
      of pregnancy: transabdominal versus transvaginal sonography.
AB  - A comparison is made between 290 patients examined using transabdominal
      sonography and 308 patients examined using transvaginal sonography. Patients with
      suboptimal menstrual histories and threatened miscarriages were excluded from
      these two groups of patients. The transabdominal and transvaginal sonography
      examinations were carried out while the patient's bladder was empty, so that
      there was no delay between the clinical and sonographic examinations. In this way
      there was no patient discomfort from a full bladder. In normal pregnancies after
      42 days of amenorrhea, the percentage visualization rates of the chorionic sac,
      of the embryo with heart activity and of the yolk sac were measured. There were
      no significant differences between the two groups. The two techniques were able
      to provide a reliable diagnosis of miscarriage on embryos >or= 4 mm or with
      chorionic sacs >or= 10 mm mean diameter. However, before 42 days of gestation,
      transvaginal sonography was better than transabdominal sonography at diagnosing
      miscarriage. The percentage of anembryonic pregnancies was higher in the
      transabdominal sonography group (21%) than in the transvaginal sonography group
      (7%), despite similar gestational ages at the time of a positive diagnosis. Thus,
      a transabdominal scan can be used after 42 days and borderline cases can be
      referred for transvaginal sonography for confirmation.

PMID- 12796901
TI  - The use of the transvaginal automated spring-loaded puncture device
      transabdominally.
AB  - Transabdominal use of a software integrated, automated, spring-loaded
      transvaginal puncture device is described. This device allows accurate, high
      velocity needle placement into sonographically targeted areas under continuous
      direct vision without the use of local anesthesia. Successful use of the device
      in seven cases is described.

PMID- 12796902
TI  - Fetal endocarditis in left atrial isomerism - a case report.
AB  - We report a case of fetal endocarditis coexisting with a congenital heart defect:
      a common atrium (left atrial isomerism) with complete congenital heart block. The
      case was studied by echocardiography from 32 to 39 weeks of gestation. A
      postmortem examination was carried out a few hours after Cesarean section. The
      autopsy, histopathological and immunohistochemical findings revealed
      endocarditis. We think that abnormal turbulent systolic and diastolic flow of the
      semilunar valve, seen in fetal Doppler echocardiography, may be a sign of fetal
      endocarditis even though clear evidence of vegetations were not seen.

PMID- 12796903
TI  - Prenatal diagnosis of cavernous lymphangioma of the arm.
AB  - We present a case of prenatal diagnosis of a fetal cystic hygroma of the arm
      diagnosed using ultrasound scanning in the 32nd week of gestation. This
      represents the first reported case of cystic hygroma in this location.
      Ultrasonography was useful for the assessment of fetal arm mobility and for
      monitoring the volume of the mass during the pregnancy.

PMID- 12796904
TI  - Perforation of the uterus by an invasive mole using color Doppler ultrasound:
      case report.
AB  - A case of invasive mole is presented. The diagnosis made using transabdominal
      color Doppler ultrasound was confirmed by the subsequent surgical removal of a
      large tumor. The authors suggest that the use of transabdominal color Doppler
      ultrasound shows encouraging promise in such cases and should be considered in
      addition to pelvic arteriograms.

PMID- 12796905
TI  - Prenatally diagnosed testicular torsion.
AB  - A case is reported of absent testis in a boy of 7 months who was noted to have a
      cystic intra-abdominal mass at 18-19-week prenatal ultrasound scan. This is the
      second report of prenatally detected testicular torsion, the previous case being
      noted much later in pregnancy. On both occasions, the diagnosis was only
      established after birth.

PMID- 12796906
TI  - Ultrasonographically detectable markers of fetal chromosomal defects.

PMID- 12796909
TI  - ISUOG in a united Europe and beyond.

PMID- 12796907
TI  - Mean values or lowest values of pulsatility and resistance indices?

PMID- 12796910
TI  - A new look at the foramen ovale.

PMID- 12796911
TI  - The uterine cervix, ultrasound and prematurity.

PMID- 12796912
TI  - Foramen ovale: an ultrasonographic study of its relation to the inferior vena
      cava, ductus venosus and hepatic veins.
AB  - According to the literature, oxygenated blood from the ductus venosus and hepatic
      veins may either enter the right atrium before flowing through the foramen ovale
      to the left atrium, or flow directly from the ductus venosus and the hepatic
      veins to the foramen ovale, bypassing the right atrium. To address this problem,
      103 normal fetuses were examined by two-dimensional imaging, M-mode and color
      Doppler at an average gestational age of 27 weeks (range, 15-40 weeks). The
      position of the ventricular septum and foramen ovale, and the angle and flow
      direction of the inferior vena cava, ductus venosus and hepatic veins were
      recorded. Two pathways for blood were described: a left ductus venosus-foramen
      ovale pathway that delivers blood directly to the foramen ovale circumventing the
      right atrium, and a right inferior vena cava-right atrium pathway that delivers
      blood into the right atrium through the right portion of the proximal inferior
      vena cava at an angle of 13 degrees to the long axis of the spine. The left and
      medial hepatic veins enter the left ductus venosus-foramen ovale pathway, and the
      right hepatic vein enters the right inferior vena cava-right atrium pathway. This
      supports the hypothesis that oxygenated blood from the ductus venosus and left
      hepatic veins flows directly through the foramen ovale to the left atrium
      avoiding extensive mixture in the inferior vena cava and an intermediate entrance
      to the right atrium.

PMID- 12796913
TI  - Normal Doppler flow velocity waveforms in the fetal ductus arteriosus in the
      first half of pregnancy.
AB  - Ductus arteriosus flow velocity patterns were studied in 298 women between 9 and
      25 weeks of gestation using transvaginal or transabdominal Doppler ultrasound.
      Technically acceptable recordings were first obtained at 11 weeks resulting in
      231 women for further analysis. Ductal waveforms show a significant change in
      shape from early pregnancy to mid-pregnancy, in that end-diastolic velocities are
      absent until 13 weeks, are present in 50% at 15 weeks and are present in all
      cases from 17 weeks. Regression analysis demonstrated a statistically significant
      linear increase with advancing gestational age for all flow velocity parameters
      except for the pulsatility index which remained stable during the entire study
      period.

PMID- 12796914
TI  - Early prediction of preterm delivery by transvaginal ultrasonography.
AB  - The clinical value of transvaginal ultrasonography in the evaluation of the
      uterine cervix of pregnant women was studied. Comparison with conventional
      transabdominal ultrasound in 24 pregnant subjects revealed that transvaginal
      ultrasound was superior, because the transabdominal technique usually requires a
      full bladder, which causes deformation and elongation of the cervix. Digital
      examination showed dilatation of the internal os in only ten (38.5%) of 26
      patients in whom it had previously been shown by transvaginal sonography.
      Transvaginal ultrasonography has the advantage of providing natural and objective
      information on the cervix. The values of three sonographic signs found
      transvaginally for predicting preterm delivery were evaluated in a total of 130
      at-risk patients and 129 control subjects. Shortening of the cervical length by 
      1.5 SD or more was associated with an increased risk of preterm delivery (11.3%
      vs. 2.8%, p < 0.01). A dilated internal os of more than 5 mm before 30 weeks of
      gestation was associated with preterm delivery more often than an undilated
      internal os (33.3% vs. 3.5%, p < 0.01). Dynamic changes in the degree of
      dilatation of the cervical canal which were found in nine women were
      significantly related with preterm delivery (p < 0.05). But, in the at-risk
      group, only dilatation of the internal os had a predictive value for preterm
      birth. From these data, dilatation of the internal os on transvaginal
      ultrasonography was proved to be an early and important predictor of preterm
      delivery.

PMID- 12796915
TI  - Vaginal ultrasound and cervical cerclage: a prospective study.
AB  - Vaginal ultrasound is a new technique for the objective assessment of the
      pregnant cervix. Twenty patients (21 pregnancies) were scanned at regular
      intervals throughout pregnancy after cervical cerclage by the vaginal route.
      Patients were recruited in 2 consecutive years in each of two centers with a low
      incidence of cervical cerclage (less than 0.5% of all pregnancies). Cervical
      cerclage, using Mersilene tape inserted by anterior and posterior incisions,
      positioned the cervical suture in the middle third of the cervical canal in all
      procedures (21/21). Ultrasound features including dilatation of the internal
      cervical os and herniation of the gestational sac to the level of the cervical
      suture were detected in 4/21 pregnancies at 5-7 weeks prior to delivery (21-33
      weeks). Six patients (6/21) delivered preterm (< 37 weeks) without ultrasound
      features associated with cervical incompetence. Eleven patients (11/21) had a
      closed internal cervical os throughout pregnancy that remained closed after
      removal of the cervical suture at 38 weeks. In this study ultrasound features
      associated with cervical incompetence had a sensitivity of 40% and a specificity
      of 100% in the prediction of preterm pregnancy loss in this group of patients
      undergoing cerclage. Vaginal ultrasound is a simple, non-invasive technique that
      permits the detection of ultrasound features associated with cervical
      incompetence during pregnancy in patients who have had prophylactic cervical
      cerclage at 14-16 weeks' gestation. Ultrasound features associated with cervical
      incompetence were rare in this group of patients (4/21 from an overall obstetric
      population of 8000 deliveries) indicating a prevalence of cervical incompetence
      in the range of 1 : 1000-1 : 2000 deliveries. In the majority of patients
      undergoing cerclage (11/21) the clinical diagnosis of 'cervical incompetence' was
      incorrect as shown by the detection of a normal cervical canal following removal
      of the suture at 38 weeks.

PMID- 12796916
TI  - Nuchal cord in normal third-trimester pregnancy: a color Doppler imaging study.
AB  - A prospective study was performed in a normal, unselected, population of 180
      pregnant women to assess the screening properties of color Doppler imaging in the
      detection of nuchal cord during the third trimester of pregnancy. A search was
      made for the umbilical cord position initially using conventional real-time gray
      scale imaging and subsequently using color imaging. Umbilical artery resistance
      and pulsatility indices and maximum peak systolic velocity were measured in each
      case at the level of the placental cord insertion. Forty-five (25%) cases
      examined using color imaging presented with a nuchal cord at both ultrasound
      examination and delivery. Color imaging correctly identified in utero 28 (72%)
      single and 17 (94%) multiple nuchal cords found at birth. The overall sensitivity
      of color imaging in detecting nuchal cord prenatally was greater than for gray
      scale imaging (79% compared with 33%). The sensitivity of color imaging was also
      higher after 36 weeks than before (93% compared with 67%). No difference was
      observed between the umbilical artery resistance and pulsatility indices. There
      was also no difference observed for the maximum peak systolic velocity between
      cases presenting with a nuchal cord (at both ultrasound examination and delivery)
      and controls matched for gestational age. We suggest that the clinical usefulness
      of systematic identification in utero of nuchal cord in pregnancies presenting
      with a normal fetus in the vertex position is limited, but might be of value in
      the management of breech and twin gestations, and also in the management of
      chronically growth-retarded fetuses.

PMID- 12796917
TI  - Doppler ultrasound examination of fetal renal arteries.
AB  - This study used color Doppler imaging to establish the normal values of the
      pulsatility index in the fetal renal arteries in a group of 304 uncomplicated
      singleton pregnancies. The measurements were taken between 26 and 42 weeks of
      gestation. The median was 2.79 (95% confidence interval: 2.72-2.86) for 26 weeks'
      gestation, and it then fell linearly to 1.96 (95% confidence interval: 1.92-2.00)
      at 40 weeks. Compared with values published so far in the literature, the range
      was clearly smaller. These normal values could be used as a basis for further
      investigations on these vessels.

PMID- 12796918
TI  - Transvaginal color Doppler study of middle cerebral artery blood flow in early
      normal and abnormal pregnancy.
AB  - Transvaginal color and pulsed Doppler sonography was performed on 106 singleton
      pregnant women; 75 had clinically normal pregnancies, and the remaining 31
      patients had complicated pregnancies with vaginal bleeding. The gestational ages
      ranged from the 7th to 18th menstrual weeks. The aim of the study was to
      establish the earliest gestational age at which intracranial blood flow could be
      detected, in particular in the middle cerebral artery. The intracranial
      circulation becomes visible at the 8th week of gestation (7 weeks and 3 days).
      The end-diastolic component of blood flow is inconstantly present from the 11th
      to the 13th gestational week, and is always detected thereafter. A significant
      decrease in the pulsatility index (p < 0.05) and peripheral flow impedance index
      (p < 0.001) was observed during the early weeks of pregnancy in both the normal
      and complicated pregnancies. There was no significant difference between the
      groups (p > 0.05). Results suggest that Doppler studies of middle cerebral
      arteries in early pregnancy are unlikely to be of value in identifying fetal
      hemodynamic disorders in the early stages of spontaneous abortion.

PMID- 12796919
TI  - Successful outcome after Nd : YAG laser separation of chorioangiopagus-twins
      under sonoendoscopic control.
AB  - Endoscopic laser coagulation of the chorioangiopagus was successfully performed
      at 25 weeks' gestation in a pregnancy presenting with acute polyhydramnios due to
      twin transfusion syndrome. Under local anesthesia, a rigid fetoscope housed in a
      2.7 mm diameter cannula was introduced transabdominally into the amniotic cavity
      and the communicating vessels were coagulated by Nd : YAG laser through a fiber
      that was passed down the side-arm of the cannula. There was rapid normalization
      of urine output in both fetuses and resolution of the oligo- and polyhydramnios
      in the donor and recipient twins, respectively. Furthermore, there was
      normalization in both fetal circulations, as assessed by Doppler velocimetry, and
      there was gradual resolution of the hydrops in the recipient. Two healthy babies
      were born 9 weeks after the procedure.

PMID- 12796920
TI  - Leiomyosarcoma of the bladder - ultrasonographic features.
AB  - We present a case in which the evaluation of a bladder mass revealed a
      leiomyosarcoma of the bladder. The ultrasonographic appearance of this tumor is
      described for the first time. Leiomyosarcoma of the bladder, although rare,
      should be considered in the differential diagnosis of pelvic masses.

PMID- 12796921
TI  - Doppler echocardiographic assessment of fetal cardiac function.

PMID- 12796922
TI  - Prenatal diagnosis of pectus excavatum and its relation to Down's syndrome.

PMID- 12796923
TI  - Discrimination between benign and malignant adnexal tumors.

PMID- 12796924
TI  - Computers in obstetrical and gynecological imaging.

PMID- 12796925
TI  - Standardization of ultrasonographic images: let's all talk the same language!

PMID- 12796926
TI  - Fetal laryngeal obstruction.

PMID- 12796927
TI  - First-trimester diagnosis of nuchal anomalies: significance and fetal outcome.
AB  - High-resolution real-time ultrasonography now permits the differentiation between
      nuchal translucencies and cystic hygromata of the neck in the first trimester. A
      series of 85 nuchal anomalies are presented that were diagnosed by
      ultrasonography at 9-14 weeks' gestation; their association with chromosomal
      defects and fetal outcome are also presented. Chromosomal anomalies were found in
      8/29 nuchal translucencies and in 16/56 cystic hygromata of the neck. However, in
      fetuses with normal karyotype, additional defects were diagnosed in l0/40 fetuses
      with cystic hygromata and in none with nuchal translucency. These data may be
      important for the management of these conditions and for counselling the patients
      toward further pregnancy.

PMID- 12796928
TI  - The natural history of oligohydramnios/polyhydramnios sequence in monochorionic
      diamniotic twins.
AB  - Twelve patients with monochorionic diamniotic twin pregnancies complicated by
      oligohydramnios/polyhydramnios sequence were evaluated to determine the natural
      history of this syndrome. Nine patients elected to continue their pregnancies and
      three underwent elective termination. Six of the nine continuing pregnancies
      delivered viable fetuses. Four of the nine continuing pregnancies had evidence of
      a 'stuck' twin at less than 20 weeks' gestation, and only one yielded live
      newborns (25%). Three patients diagnosed with a mild case of
      oligohydramnios/polyhydramnios sequence underwent worsening of the syndrome with
      a 'stuck' twin seen only after 26 weeks: all neonates survived. Five pregnancies
      initially diagnosed as having a 'stuck' twin showed improvement in amniotic fluid
      volume, with one actually reversing, so that the previously 'stuck' twin
      developed polyhydramnios and the co-twin became 'stuck'. In summary, among the
      nine non-aborted pregnancies managed conservatively, 12 of 18 fetuses (67%)
      survived. When the diagnosis of 'stuck' twin was made at <or= 20 weeks, only two
      of eight (25%) lived. These observations suggest that the
      oligohydramnios/polyhydramnios sequence is a dynamic process with wide and often
      unpredictable fluctuations in amniotic fluid volume.

PMID- 12796929
TI  - The clinical significance of resolving polyhydramnios.
AB  - Polyhydramnios is associated with multiple maternal and fetal abnormalities.
      Although the risks of persistent polyhydramnios are well described, the clinical
      implications of polyhydramnios that resolves prior to delivery are not. Thirty
      four non-diabetic patients with resolving polyhydramnios were studied. An
      amniotic acid index of >or= 20 was used to define polyhydramnios. Antepartum and
      postpartum outcomes were compared with those patients with persistent
      polyhydramnios, and a control group of 102 singleton term deliveries. Patients
      with resolving polyhydramnios did not have a significant increase in congenital
      anomalies. An 8% incidence of congenital anomalies was noted in patients with
      persistent polyhydramnios; this was significant compared with controls (p <
      0.05). Idiopathic resolving polyhydramnios was associated with a higher mean
      birth weight (p < 0.05) than controls, with significantly more babies weighing
      more than 4200 g. An increase in placental thrombus formation was noted in
      patients with idiopathic resolving and persistent polyhydramnios compared to the
      control group (p < 0.01). The etiology of this is unclear. Obstetricians should
      be aware of the risk of macrosomia and the possibility of placental disease in
      these fetuses.

PMID- 12796930
TI  - Does the amniotic fluid index change over a short-term time interval?
AB  - The amniotic fluid index (AFI) is a rapid and simple technique that is commonly
      used to assess amniotic fluid volume. It is commonly used in conjunction with
      other tests of fetal well-being that extend over a variable time interval. The
      data on interobserver and intraobserver variability have not stated the interval
      between measurements, although it is likely that they have been repeated
      immediately. In this study an AFI was repeated after a short time interval to
      assess whether a significant difference exists, as this may be clinically
      relevant. In 91 patients, the AFI was performed at the beginning and end of an
      ultrasound scan for either growth and development, or for Doppler velocimetry.
      The interval between the two measurements was 30-45 min, and the respective
      results were as follows: mean 18.4 vs. 18.7; standard deviation 4.2 vs. 3.9;
      minimum value 10.1 vs. 11.0 and maximum value 35.0 vs. 30.0. There were no
      significant differences between the two measurements (p > 0.133; d.f. = 90) and
      the correlation coefficient was 0.874 (p < 0.0001). These results validate the
      reproducibility of the AFI over a 30-45 min interval, during which time most
      adjunctive tests are usually completed. Therefore, the timing of the AFI in
      relation to the other tests is not critical.

PMID- 12796931
TI  - Intrauterine fetal transfusion, 1963-90.
AB  - The first fetal transfusion was performed at the National Women's Hospital in
      Auckland in 1963. From that time until the end of 1990, a total of 1041
      transfusions have been completed on 459 fetuses. The survival rate for affected
      pregnancies rose significantly from 39% in 1963-65 to 90% in 1986-90. The initial
      409 patients had fetal transfusions performed via the intraperitoneal cavity with
      X-ray guidance. Since 1986, 50 pregnancies have been treated with intravascular
      transfusions under ultrasound guidance and 45 fetuses survived.

PMID- 12796932
TI  - Early prediction of uteroplacental complications of pregnancy using Doppler
      ultrasound, placental function tests and combination testing.
AB  - In a prospective, blind study of 183 unselected women attending for routine
      booking scan with a singleton pregnancy at 16-24 weeks' gestation, uteroplacental
      resistance index, and peripheral levels of alpha-fetoprotein, human chorionic
      gonadotropin, human placental lactogen, Schwangerswaft protein, pregnancy
      associated placental protein A and insulin-like growth factor (IGF) binding
      protein 1 were measured. High levels of alpha-fetoprotein and IGF 1 binding
      protein 1 (> 90th centile) were associated with small-for-gestational age babies
      (< 10th centile) (sensitivity 24% and 22%; specificity 90% and 91%). High levels
      of alpha-fetoprotein, human chorionic gonadotropin and pregnancy-associated
      placental protein A (> 90th centile) were associated with one or more of three
      severe complications of pregnancy: very small-for-gestational age (< 3rd
      centile), severe proteinuric hypertension or intrauterine death (sensitivity 20%,
      20% and 57%; specificity 90%, 95% and 91%, respectively). A uteroplacental
      resistance index > 90th centile was also associated with small-for-gestational
      age and severe complications (sensitivity 24% and 50%, specificity 90% and 90%).
      A combination of resistance index and a placental function test improved the
      prediction for a group of patients that included any complications (sensitivity
      31% and specificity 89%). Doppler ultrasound was a more efficient predictor than
      individual placental function tests but screening predictions can be improved by
      combining Doppler parameters and placental protein estimations. Combinations of
      placental function tests might provide equivalent, or complementary, information.
      This preliminary work demonstrates the potential value of combining biophysical
      and biochemical tests to predict complications of pregnancy.

PMID- 12796933
TI  - Validity of pulsatility and resistance indices in classification of adnexal
      tumors with transvaginal color Doppler ultrasound.
AB  - Transvaginal pulsed color Doppler ultrasound was used to examine 72 patients with
      a pelvic mass preoperatively. Tumor morphology was assessed, prominent areas of
      vascularization within the tumor were observed and the pulsatility index and the
      resistance index of tumor and uterine arteries were measured. Flow velocity
      waveforms with low pulsatility are considered to reflect neovascularization. The
      ultrasound diagnoses were compared with histopathological or cytological
      diagnoses. There were 61 benign, eight malignant and three borderline cases. In
      75% of the malignant and 23% of the benign tumors, an intratumoral flow with a
      low pulsatility was detectable. The mean pulsatility index of tumor blood vessels
      was 1.2 in benign, 0.7 in malignant and 0.6 in borderline neoplasms. The
      corresponding mean resistance index values were 0.6, 0.5 and 0.5. The differences
      were not significant and the overlap between the malignant and benign lesions was
      large. The pulsatility index and resistance index of uterine arteries were
      significantly decreased in malignant tumors. The results show that, using a cut
      off resistance index value of 0.6, the sensitivity and specificity of color
      Doppler in the detection of malignant and potentially malignant tumors were 82%
      and 72%, respectively. However, a practical cut-off level for either pulsatility
      or resistance indices, that could assist in differentiating between malignant or
      benign lesions, does not seem to exist.

PMID- 12796934
TI  - Ultrasound-controlled removal of a dislocated intrauterine device in the first
      trimester of pregnancy: a report of 26 cases.
AB  - Intrauterine, ultrasound-guided removal of a copper-releasing intrauterine
      contraceptive device (IUCD) was carried out in 26 first-trimester pregnancies. In
      all the pregnancies, the string of the device had retracted into the uterine
      cavity. The total loss of pregnancies was 46%, while 36% of the initially
      uncomplicated single pregnancies ended in a spontaneous abortion. The time lag
      between the removal of the IUCD and clinical abortion was 21.5 days (range 3-48
      days). A fundal location of the IUCD and failure to remove the IUCD by the first
      traction were common features in the abortion group. A total of 14 of the
      pregnancies resulted in a liveborn baby, and the incidence of complications after
      the 20th gestational week was not increased compared with the normal population.

PMID- 12796935
TI  - Ovarian cysts during pregnancy: the role of ultrasonically guided transvaginal
      aspiration.
AB  - Three cases of ovarian cysts, with a mean diameter measuring more than 6 cm
      during the second trimester of pregnancy, were aspirated transvaginally, guided
      by ultrasound. All cysts were unilocular, thin-walled with no internal echoes.
      Cytological examination of the aspirated fluid revealed benign luteinized
      granulosa cells. No complications occurred and the pregnancies continued to full
      term. It is believed that needle aspiration of simple ovarian cysts of 6 cm
      diameter or more during pregnancy is a safe and effective treatment that is
      capable of reducing the risk of torsion, hemorrhage or rupture and avoiding
      unnecessary laparotomy.

PMID- 12796936
TI  - Current status of vaginosonography: a world-wide inquiry.
AB  - In the last 5 years, vaginosonography has become a routine procedure in
      obstetrics and gynecology. Many obstetricians, gynecologists, radiologists and
      ultrasonographers have recognized the advantages of this method. Nearly all
      manufacturers of ultrasound equipment offer several types of vaginal probes. The
      rapid spread of vaginosonography has also led to some disadvantages concerning
      the lack of standardized terminology and image display. In this study, we
      collected data about the current standards of vaginosonography. To obtain data,
      questionnaires were sent out to the 1107 Departments of Obstetrics and Gynecology
      in the FIG0 Registry 1985. In the accompanying letter, the chairman was asked to
      hand over the questionnaire to the appropriate specialist. The questionnaire was
      designed to gather information about the personnel performing vaginosonography
      and the techniques, transducer frequency, position of the patient and image
      display used. A total of 369 responses were received. Vaginosonographic
      investigations were performed in 84% of the University Departments of Obstetrics
      and Gynecology. In 90% of these, vaginosonography was performed by the
      obstetrician or gynecologist, in 4% by the radiologist and in 6% by the
      technician. Most departments preferred end-firing transducers. The numbers of
      electronic and mechanical probes were nearly identical (56% vs. 44%). The
      preferences for a scanner with a narrow (less than 120 degrees ) or wide angle
      (more than 120 degrees ) were very similar (53% vs. 47%). More than half of the
      responders (54%) used a transducer frequency of 5 MHz, while 46% preferred
      scanners with a frequency between 5.5 and 7.5 MHz. In 55%, the gynecological
      examination table was considered to be superior to a flat table. Of the
      responders, 52% projected the apex of the vaginal probe to the bottom of the
      ultrasound monitor. This was particularly the case in Europe (63%). Questioned
      about a preference for a particular orientation in the future, an additional 7%
      voted to change to this mode of image display world-wide. When performing a
      sagittal section, if the probe was projected to the bottom of the screen,
      dorsally located to the structures were projected twice as often to the left of
      the screen as to the right.

PMID- 12796937
TI  - Fetal laryngeal obstruction: sonographic detection.
AB  - A patient was referred at 21 weeks' gestation for unexplained fetal lung
      hyperechogenicity and ascites. Amniocentesis was normal. Fetal lung biopsy was
      consistent with the clinical diagnosis of cystic adenomatoid malformation of the
      lungs. However, autopsy of the stillborn infant demonstrated a cartilaginous bar,
      causing total laryngeal obstruction. The distinctive ultrasonographic appearance
      is presented.

PMID- 12796938
TI  - Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome: a case report.
AB  - At 20 weeks of gestation, a typical combination of a massive enlargement of the
      right fetal leg and multiple cystic lesions was detected at ultrasound
      examination. Color-coded Doppler examination revealed no arteriovenous fistulae.
      These findings allowed an in utero diagnosis of the Klippel-Trenaunay-Weber
      syndrome, which was confirmed after subsequent termination of the pregnancy. The
      severe malformation involved the upper and lower right leg. No arteriovenous
      fistulae were found.

PMID- 12796941
TI  - Color Doppler imaging of the uterine artery in pregnancy.

PMID- 12796940
TI  - Diagnostic ultrasound: bioeffects and safety.

PMID- 12796939
TI  - The acardiac twin: a case report using color Doppler ultrasonography.
AB  - The use of color Doppler sonography has expanded our understanding of the normal
      and abnormal pregnancy. A case is presented here in which color Doppler imaging
      was utilized to confirm a long-held theory concerning the strikingly abnormal
      dynamics of arterial flow to an acardiac twin and observations are also presented
      concerning the possible route of venous return contrary to presumed theories
      established within the literature.

PMID- 12796942
TI  - Second World Congress of ISUOG: meeting report.

PMID- 12796943
TI  - Presentation of the 1992 Ian Donald Gold Medal to Stuart Campbell.

PMID- 12796944
TI  - Ultrasound - an indispensable diagnostic tool for the obstetrician.

PMID- 12796945
TI  - Safety of routine ultrasound.

PMID- 12796946
TI  - Measuring volume flow with Doppler ultrasound-an old nut.

PMID- 12796947
TI  - Placental ultrasonographic measurement: what can we learn and is it worth doing
      routinely?

PMID- 12796948
TI  - Routine ultrasonography in utero and subsequent vision and hearing at primary
      school age.
AB  - The study was performed to investigate any associations between routine
      ultrasonography during pregnancy and subsequent reduced vision and/or hearing
      among children. A follow-up was carried out of primary school children born to
      women who took part in two randomized, controlled trials of routine
      ultrasonography during pregnancy. Of 2428 eligible singletons, 2161 (89%) were
      followed up with a parental questionnaire and with information from maternal and
      child health centers. Parents assessed vision and hearing in their children and
      reported their observations in questionnaires. At the age of 7 years, the
      children were also screened with bilateral visual acuity tests and pure tone
      audiometry at public maternal and child health centers. No significant
      differences between ultrasound-screened children and their controls were found in
      the parental assessment of vision or hearing. The objective tests did not show
      any significant differences between children in the two groups with regard to
      visual acuity or hearing. The risk of reduced vision or hearing was no greater
      for children of mothers who had been offered routine ultrasonography during
      pregnancy than for those whose mothers had not received that offer.

PMID- 12796949
TI  - The role of transvaginal sonography in the early detection of congenital heart
      disease.
AB  - The antenatal diagnosis of congenital heart disease by fetal echocardiography is
      rarely achieved before 18-20 weeks' gestation. Transvaginal sonography allows
      examination of fetal anatomy at earlier gestations than the transabdominal
      approach. In a screening study of 270 low-risk women between 8 and 14 weeks'
      gestation using a 5 MHz vaginal transducer, it was possible to obtain adequate
      four-chamber views in over 70% from 12 weeks. In a second study of 32 women at
      high risk of congenital heart disease scanned between 14 and 15 weeks' gestation,
      satisfactory views were obtained transvaginally in 21 women. Seven of the
      remainder had normal cardiac anatomy confirmed by transabdominal scanning. In
      three of the four where normal cardiac anatomy could not be demonstrated by
      either transvaginal or transabdominal scanning, severe congenital heart disease
      was diagnosed and later confirmed. It is unlikely that transvaginal sonography
      will replace abdominal scanning for the screening of low-risk pregnancies, but it
      is a valuable addition to the early examination of those women identified as
      being at high risk of congenital heart disease.

PMID- 12796950
TI  - The sonographically thick placenta: a predictor of increased perinatal morbidity
      and mortality.
AB  - In order to determine the prevalence and significance of sonographically thick
      placentas, we reviewed the computerized records of 18 827 viable, singleton
      pregnancies. Of these, 116 (0.6%) had thick placentas diagnosed by ultrasound
      examination. Perinatal mortality was markedly increased among pregnancies with
      thick placentas (odds ratio = 13.1, 95% confidence limits (CL) = 8.3-20.8),
      accounting for 6.2%; of the total. The rates of abruptio placentae (odds ratio =
      2.9, CL = 1.1-8.1), neonatal intensive care unit admissions (odds ratio = 4.6, CL
      = 3.1-6.9) and anomalies (odds ratio = 8.4, CL = 4.9-14.4) were also
      significantly increased among the thick placenta cohort compared to controls. The
      106 liveborn neonates with thick placentas had lower Apgar scores, were delivered
      at an earlier gestational age, and weighed less than controls. Anomalies, hydrops
      fetalis and abruptio placentae complicated 16 of the 24 cases of perinatal
      mortalities. Sonographically thick placentas should alert the clinician to the
      possibility of compromised perinatal outcome.

PMID- 12796951
TI  - Transvaginal ultrasound: does it help in the diagnosis of placenta previa?
AB  - The purpose of this study is to evaluate the use of transvaginal ultrasound in
      the diagnosis of placenta previa and to assess the risk of bleeding secondary to
      the placement of the vaginal transducer. Thirty-eight patients with an estimated
      gestational age equal to or greater than 26 weeks and the diagnosis of suspected
      placenta previa gave their consent and were randomized to two groups.
      Randomization was stratified by patient weight and anterior or posterior
      placental location. Group 1 (n = 20) had complete obstetric ultrasounds using
      linear and sector transducers. Group 2 (n = 18) had similar examinations followed
      by transvaginal ultrasound scans. Patients were rescanned to follow placental
      location and fetal growth parameters. On abdominal ultrasound, the posterior
      placenta (n = 17) was often shadowed by fetal parts. The ease of placental
      visualization was rated on a four-point scale with 1 being the clearest. The mean
      clarity score for posterior placentas on abdominal ultrasound in Group 2 was 1.6
      and on transvaginal ultrasound was 1.0, p < 0.04. The use of transvaginal
      ultrasound consistently revealed greater clarity of diagnosis in these patients.
      No patient in either group experienced increased vaginal bleeding following the
      scanning sessions. Transvaginal ultrasound was most beneficial for those patients
      with posterior placenta previas because of increased clarity of diagnosis,
      decreased time of scanning, and no increased incidence of hemorrhage.

PMID- 12796952
TI  - Color Doppler imaging of the uterine artery in pregnancy: normal ranges of
      impedance to blood flow, mean velocity and volume of flow.
AB  - In a cross-sectional study of 215 healthy women with singleton pregnancies at 18
      42 weeks' gestation, color Doppler imaging was used to identify the main uterine
      arteries for subsequent pulsed Doppler studies. Flow velocity waveforms were
      obtained and indices of impedance, mean blood velocity and vessel diameter were
      measured, and the total volume of blood flow to the uterus was calculated.
      Impedance to flow decreased, I whereas blood velocity and volume flow increased
      significantly with gestation. Furthermore, impedance to flow was lower and
      velocity higher in the placental uterine artery, i.e. closest to the main bulk of
      the placenta, than in the non-placental artery.

PMID- 12796953
TI  - Potential for diagnosing imminent risk to appropriate- and small-for-gestational
      age fetuses by Doppler sonographic examination of umbilical and cerebral arterial
      blood flow.
AB  - In a prospective study, 215 pregnancies of known gestational age were
      investigated using Doppler sonography. Multiple pregnancies and pregnancies
      complicated by fetal malformations were excluded. A pulsed Doppler machine was
      used to record the flow velocity waveforms in the umbilical artery (UA) and
      middle cerebral artery (MCA). The pulsatility index (PI) of both vessels and the
      ratio of PI UA to PI MCA were calculated. A total of 127 pregnancies ended in the
      birth of appropriate-for-gestational age babies with no perinatal problems; these
      formed the normal group (Group A). Of the 88 pregnancies which made up the risk
      group, 17 were appropriate-for-gestational age babies with perinatal problems
      (Group B), 55 were small-for-gestational-age babies with no perinatal problems
      (Group C), and 16 were small-for-gestational age babies with perinatal problems
      (Group D). Normal ranges were calculated based on the results for Group A; the
      measured values for the risk groups were then compared to these. There were
      highly significant differences between values obtained from the risk groups and
      those of Group A with the exception of the umbilical artery in Group B and the
      middle cerebral artery in Group C. The best results came from the values for MCA
      in Group B (sensitivity = 71%), UA in Group D (sensitivity = 75%), and the PI
      ratio UA : MCA in Group D (sensitivity = 81%). The sensitivity for the ratio in
      Group D increased to 93% if only the last measurement for each patient taken
      within 14 days of delivery was analyzed. A drop in the MCA PI in appropriate-for
      gestational-age fetuses was the best indicator of imminent risk of hypoxemia. The
      PI ratio of UA : MCA is valuable in monitoring small-for-gestational-age fetuses,
      particularly those with high UA PI levels, as a rise in the ratio provides an
      early indication of fetal risk.

PMID- 12796954
TI  - Comparison of the prognostic value of pulsed Doppler blood flow parameters to
      predict SGA and fetal distress.
AB  - A total of 219 women with complicated pregnancies had Doppler assessment of
      uteroplacental arteries, the umbilical artery, the fetal common carotid artery
      and the descending thoracic aorta to determine the prognostic value of Doppler
      examinations to predict the birth of a small-for-gestational-age (SGA) infant
      with or without fetal distress. Preliminary reproducibility studies showed that
      the resistance index, pulsatility index and intensity weighted flow velocity had
      the lowest coefficients of variation. Data on the systolic/diastolic ratio and
      mean blood flow volume were, therefore, not considered for further evaluation.
      Measurements were classified according to the time interval of the examination to
      the delivery of the baby according to the following groupings: 0-14 days, 15-28
      days and 29-42 days. For evaluation of the SGA fetus complicated by fetal
      distress, only measurements within 2 weeks of delivery were analyzed. Significant
      differences were calculated by considering the area below the receiver operator
      characteristic (ROC) curves. Only Doppler studies of the uteroplacental arteries
      (mainly resistance index) were predictive of the later development of the SGA
      fetus. All fetal parameters showed an increasing improvement in the predictive
      capacity for an SGA infant, the closer the measurements were made to the time of
      delivery. This improvement was not observed for uteroplacental vessels. The
      resistance index of the uteroplacental vessels was significantly higher in SGA
      pregnancies complicated by fetal distress compared to SGA pregnancies alone.
      However, ROC analysis revealed that fetal Doppler velocimetry was more strongly
      related to fetal distress than SGA only. The single best fetal parameter was the
      mean velocity in the fetal descending thoracic aorta but the velocity ratio of
      the fetal common carotid artery over the fetal descending thoracic aorta had the
      highest predictive capacity for the SGA pregnancy complicated by fetal distress.

PMID- 12796956
TI  - Changes in tubal blood flow in evaluating ectopic pregnancy.
AB  - Ectopic pregnancy is not recognized in 5523% of all cases using state-of-the-art
      diagnostic procedures. In this study, blood flow in tubal arteries was measured
      using a transvaginal duplex Doppler ultrasonography system. A 3.5 MHz Doppler
      transducer coupled to a 5 MHz imaging transvaginal sector probe was used to
      depict flow characteristics in the tubal branch of the uterine artery. This was
      performed in 102 patients. There was a significant increase in the blood flow on
      the tubal gestation side (p < 0.0001; z = -4.08). This between-side difference
      was determined using qualitative frequency shift analysis. The mean reduction in
      the resistance index on the side with the ectopic pregnancy as compared to the
      contralateral side was 15.6%. These changes appear to be due to trophoblast
      invasion. Between-side differences showed no dependence on gestational age
      (between gestational weeks 4 and 12 postmenstruation). We compared these data
      with those from three control groups ('early viable intrauterine pregnancy',
      'early intrauterine pregnancy failure', 'non-gravid state'). In all these control
      groups, the impedance to flow, expressed as 'resistance index', showed no
      significant between-side difference. All control groups had significantly higher
      mean resistance index values than the ectopic pregnancy side, but did not differ
      from the contralateral side of the ectopic pregnancy group. The advantages of
      this new method in diagnosing ectopic pregnancy are early detection, non
      invasivity, and immediate results.

PMID- 12796955
TI  - Maternal hyperoxygenation: a fetal blood flow velocity prognosis test in small
      for-gestational-age fetuses?
AB  - Maternal hyperoxygenation tests were performed in 20 small-for-gestational age
      fetuses using 8 l/min of 70% humidified oxygen given for 20 min through a face
      mask. Assessments were made of the fetal blood flow velocity, and the placental
      resistance index, cerebral resistance index and cerebroplacental ratio were
      calculated in 78 normal pregnancies and in the 20 small-for-gestational-age
      fetuses during the hyperoxygenation test. The test was positive when the velocity
      indices increased by more than 10%. The reference ranges for placental and
      cerebral resistance indices were derived from the data measured in the 78 normal
      pregnancies. Of the 20 small-for-gestational-age fetuses, three had a normal
      placental resistance index with a negative oxygen test response and a good fetal
      outcome. Seven had a mild increase in placental resistance index (> +2SD) and a
      brain-sparing effect was observed (cerebral resistance index < -2SD or
      cerebroplacental ratio < l). In these seven fetuses, the fetal outcome was not
      poor, whether the oxygen test response was negative or positive. Ten of the 20
      small-for-gestational-age fetuses had no umbilical diastolic flow (placental
      resistance index = 1) and a brain-sparing effect. Their outcome was strongly
      dependent on the oxygen test response: a positive response indicated a good
      prognosis, a negative one a poor fetal outcome.

PMID- 12796957
TI  - Cephalocele and cystic hygroma: diagnosis and differentiation in the first
      trimester of pregnancy with transvaginal sonography. Report of two cases.
AB  - Two case reports are presented of fetuses with malformations in the neck region,
      detected in the first trimester of pregnancy by transvaginal ultrasonography. In
      one fetus a septated cystic hygroma was visualized. Trisomy 18 was found. The
      other fetus presented with a cephalocele. The ultrasound diagnosis was confirmed
      at autopsy in both cases. Sonographic criteria to distinguish between cystic
      hygroma and occipital cephalocele in the first trimester of pregnancy are
      discussed.

PMID- 12796958
TI  - Prenatal diagnosis of placenta previa/accreta with color Doppler ultrasound.
AB  - A case of placenta previa/accreta was diagnosed at 23 weeks' gestation using
      color Doppler ultrasound. Imaging showed an unusually intense blood flow within
      the placental sonolucent spaces and the hypervascularization patterns within the
      placental and the non-placental tissues. Highly pulsatile venous flow patterns
      were detected within the placental blood lakes and the subplacental venous
      complex. A strong association between the lacunar flow pattern and the abnormally
      adherent placentation was confirmed by the color Doppler sonographic findings.

PMID- 12796959
TI  - Fallopian tube carcinoma: recent diagnostic approach by color Doppler imaging.
AB  - A case of primary adenocarcinoma of the Fallopian tube is presented. The
      diagnosis was made preoperatively by transvaginal color Doppler imaging. The
      tumor revealed areas of neovascularization with characteristic low impedance
      (resistance index, 0.35) and high blood flow velocity (peak systolic velocity,
      16.7 cm/s).

PMID- 12796960
TI  - Doppler assessment of the normal early fetal circulation.
AB  - Combined transvaginal and transabdominal Doppler ultrasound allows recording of
      fetal intra- and extracardiac flow velocity waveforms in late first- and early
      second- trimester pregnancies. At 10-12 weeks, end-diastolic flow velocities were
      always absent in the fetal descending aorta and umbilical artery, but were
      present in over half of the intracerebral artery waveforms. The pulsatility index
      in the three vessels decreased significantly with advancing gestational age,
      suggesting a reduction in fetal and umbilical placental vascular resistance. Peak
      velocities during atrial contraction (A-wave) were nearly twice as high as those
      during early diastolic filling (E-wave), reflecting low ventricular compliance.
      Continuous forward flow in the umbilical vein was associated with a pulsatile
      systolic and diastolic forward flow in the ductus venosus. Retrograde flow was
      only present in the inferior vena cava.

PMID- 12796962
TI  - Get to know your machine.

PMID- 12796961
TI  - Tamoxifen: vaginosonography and color Doppler assessment of the uterus.

PMID- 12796963
TI  - Ultrasound indices of ovarian function.

PMID- 12796964
TI  - The role of ultrasound in the diagnosis of breast abnormalities.

PMID- 12796965
TI  - Sonography of fetal Dandy-Walker malformation: a reappraisal.
AB  - Thirty-four cases of fetal Dandy-Walker malformation recognized in utero with
      ultrasound between 16 and 37 weeks' gestation are reported. In each case a
      qualitative examination of the posterior fossa structures was performed,
      including the cerebellar hemispheres, cerebellar vermis, fourth ventricle and
      cisterna magna. In each case, the transverse cerebellar diameter and the depth of
      the cisterna magna were measured in a standard transcerebellar view of the fetal
      brain. The atrial width of the lateral ventricles was also assessed. The
      transverse cerebellar diameter was abnormal in 15 cases, the cisterna magna depth
      was abnormal in 33, and the atrial width was abnormal in 30. It is concluded that
      measurement of the transverse cerebellar diameter is unreliable in predicting
      fetal Dandy-Walker malformation. Measurements of the cisterna magna and atrium
      seem to be more valuable, although the real sensitivity remains unclear. In
      pregnancies at risk for fetal Dandy-Walker malformation, the sonographic
      examination should not be limited to the cerebral ventricles and transcerebellar
      view but should include a detailed evaluation of all the different anatomical
      components of the posterior fossa, especially the fourth ventricle and inferior
      cerebellar vermis.

PMID- 12796966
TI  - Coronal transcerebellar diameter: an alternate view.
AB  - Evaluation of the fetal cerebellum in the axial plane has become an important
      part of obstetric sonography. We report our experience with an alternate view,
      the coronal transcerebellar view, in 134 fetuses at gestational ages of 13-30
      weeks. There is a linear first-order correlation between axial and coronal
      transcerebellar diameters. Additionally, the coronal view was more reliably
      obtained, especially at gestational ages between 24 and 30 weeks. We believe that
      this view warrants further study, particularly in pathological states.

PMID- 12796967
TI  - The natural history of isolated fetal hydrothorax.
AB  - We reviewed the prenatal course and outcome of 11 fetuses with isolated
      unilateral or bilateral hydro thoraces identified between 14 and 34 weeks'
      gestation, in the absence of invasive fetal intervention. Four of these fetuses
      died, three in utero and one in the newborn period. Six of seven survivors had
      resolution of hydrothorax before birth. Eight of the 11 fetuses had unilateral
      and three bilateral hydrothoraces. Six of the eight fetuses with unilateral
      hydrothorax survived, whereas one of the three with bilateral hydrothoraces
      lived. Six of the 11 pregnancies were complicated by polyhydramnios; four of
      these six fetuses died. One fetus was found to have trisomy 21. It is difficult
      to draw firm conclusions from the small number of patients in this report because
      of the wide range of outcomes found for the sonographic variables described. This
      series shows, however, a tendency to complete resolution of primary unilateral
      fetal hydrothorax, with good outcome, particularly in second-trimester fetuses
      without polyhydramnios.

PMID- 12796968
TI  - Three-dimensional ultrasound of fetal surface features.
AB  - This paper presents preliminary results of techniques which permit acquisition
      and display of three-dimensional fetal anatomy using ultrasound image data
      collected as two-dimensional planar images with commercially available equipment.
      A precision translational stage was used which permitted the transducer position
      and orientation in the volume to be accurately determined. Ultrasound video image
      data were digitized into a personal computer together with transducer position
      and orientation information. All image and position data were subsequently
      transferred to a graphics workstation. Gray-scale ultrasound data were three
      dimensionally filtered, thresholded and analyzed using maximum intensity,
      variable transparency and surface rendering techniques to evaluate the fetal
      surface. Images of arbitrary orientation were displayed interactively on a
      graphics workstation. Our results demonstrate the potential of three-dimensional
      ultrasound as a technique for visualization of fetal surfaces, extremities and
      internal anatomy. Three-dimensional ultrasound offers potential advantages over
      existing diagnostic methods since it is non-invasive and offers interactive
      review and viewing optimization after fetal scanning.

PMID- 12796969
TI  - Normal fetal cardiac measurements derived by cross-sectional echocardiography.
AB  - Cardiac structures have been measured in normal fetuses by cross-sectional
      echocardiography to establish a range of normal values. Gestational ages varied
      from 16 weeks to term. The cardiac structures measured were left and right
      ventricular width (n = 337), aortic root diameter (n = 296), pulmonary artery
      diameter (n = 312), mitral valve orifice (n = 159), and tricuspid valve orifice
      (n = 161). The lengths of the left and right ventricles were measured in 100
      fetuses. Normal ranges were constructed using real-time ultrasound images which
      can be readily used in routine practice. Measurement of cardiac structures is an
      aid to the study of cardiac abnormalities and the availability of normal ranges
      of measurements of fetal cardiac structures may help to confirm and define
      suspected cardiac malformation during routine screening.

PMID- 12796970
TI  - Fetal atrioventricular and outflow tract flow velocity waveforms during conducted
      and blocked supraventricular extrasystoles.
AB  - Maximum flow velocity waveforms at atrioventricular and outflow tract level were
      studied cross-sectionally in 19 human fetuses with conducted and/or blocked
      supraventricular extrasystoles ranging from 25 to 38 weeks of gestation. At
      outflow tract level, peak systolic velocity and acceleration time for
      extrasystolic and post-extrasystolic beats were compared with those for the
      immediately preceding normal beat. Regression lines were calculated for peak
      systolic velocities with filling time. At atrioventricular level, peak-E wave and
      peak-A wave velocities and E/A ratio for the extrasystolic and post-extrasystolic
      beats were compared with those for the normal beat. At all levels, time-averaged
      velocities were compared with reference charts standardized for gestational
      age.Peak systolic velocity and acceleration time during the post-extrasystolic
      beat were higher than during the normal beat; the Frank-Starling mechanism, post
      extrasystolic potentiation as well as reduced ventricular afterload may all play
      a role in this. At all measuring levels, time-averaged velocity during the
      extrasystolic beat was strikingly lower than the reference velocities. It is
      postulated that the increased blood volume and contraction force during the post
      extrasystolic beat cause the valve area to become larger, resulting in a relative
      decrease in velocities measured by Doppler ultrasound.

PMID- 12796971
TI  - Investigation of the human corpus luteum by ultrasonography: a proposed scheme
      for clinical investigation.
AB  - The corpus luteum was investigated in 18 women undergoing hysterectomy.
      Preoperative ultrasonography with measurements was performed before the corpus
      luteum was extirpated, weighed, inspected and the diameters were measured. The
      concentrations of progesterone and estradiol were also determined in peripheral
      serum. The ultrasound pictures show that the corpus luteum has a slightly cloudy
      central part, which can vary from hypoechoic to hyperechoic. The peripheral part
      (corpus luteum 'wall') has a stronger echo and the maximal and minimal
      thicknesses can be measured. The results showed correlations between ultrasound
      measurements and anatomical measurements for wall thickness, outer diameter,
      inner diameter and wall area of the corpus luteum (n = 12, p < 0.02-0.0001).
      Moreover, all mid-luteal corpora lutea with a hypoechoic central part (five of 13
      women) on ultrasound scan had a cystic central structure. Based on these
      findings, we suggest that an ultrasound investigation of the corpus luteum in the
      mid-luteal phase should use the following criteria to classify it into four
      types. Type a: hypoechoic central part with wall of < 3 mm; type b: hyperechoic
      central part with wall of < 3 mm; type c: hypoechoic central part with wall of
      >or= 3 mm; and type d: hyperechoic central part with wall of >or= 3 mm. The
      finding of a hypoechoic central region with a thin wall (< 3 mm) may indicate
      corpus luteal insufficiency, since significantly lower serum progesterone levels
      were found in women with this type of corpus luteum.

PMID- 12796972
TI  - Intraovarian Doppler velocimetry in ovulatory, dysovulatory and anovulatory
      cycles.
AB  - We have evaluated 48 spontaneous ovarian cycles in 23 women by transabdominal
      Doppler ultrasound. A total of 1064 intraovarian flow velocity waveform
      recordings were obtained. The ultrasound assessment of follicular growth, and
      changes in the concentrations of urinary luteinizing hormone and serum
      progesterone were used to classify the cycles. After follicular rupture (and
      presumed ovulation) in 30 cycles, the intraovarian flow velocity waveform
      (dominant ovary) showed a turbulent flow during the luteal phase ('luteal
      conversion'). The maximal resistance index was lower compared to values obtained
      during the follicular phase, and from the contralateral ovary. The intraovarian
      flow velocity waveform from 12 abnormal cycles showed similar quantitative and
      qualitative changes. When ovulation did not occur (three cases of the luteinized
      unruptured follicle syndrome, three anovulatory cycles), there was no evidence of
      'luteal conversion' and the velocimetry values were similar throughout the study.
      Intraovarian Doppler velocimetry makes it possible to distinguish between
      ovulatory and anovulatory cycles, and provides a non-invasive diagnosis of the
      luteinized unruptured follicle syndrome.

PMID- 12796973
TI  - The value of ultrasonic examination to detect and diagnose breast carcinomas.
      Analysis of the results obtained in 125 tumors using radiographic and ultrasound
      mammography.
AB  - A series of 125 breast carcinomas studied by both radiological and ultrasound
      mammography, and which were observed in 102 patients, is presented. Of the
      lesions, 76.5% were less than 20 mm in diameter, and 16.8% had a diameter 10 mm
      or less. Sixteen lesions were in situ or microinvasive. Analysis of the results
      shows a 40.8% rate of false-negative results with radiological mammography, when
      only 'highly suspicious' and 'suspicious' images are considered. This figure is
      reduced to 28% when 'benign-appearing' masses are included in the computation.
      Using similar diagnostic categories, the false-negative rates obtained with
      ultrasound mammography were 14.4% and 12.8%, respectively. Combining radiological
      and ultrasound mammography resulted in a dramatic decrease in the false-negative
      rate to 4% The number of false-negative results observed with either radiological
      or ultrasound mammography was in the higher range of reported values when
      compared to selected studies. However, they may, in fact, closely reflect the
      real performance of these investigations, as they are available to patients in
      everyday clinical practice. Analysis of the data shows that radiological
      mammography is less efficient in younger patients. The mean age of the patients
      in the radiological mammography positive group was 54.3 +/- 1.2 years, as opposed
      to 47.5 +/- 2.1 (p = 0.004) in the radiological mammography negative group. In
      contrast, the efficiency of ultrasound mammography is independent of the
      patient's age, and consequently of breast density. In this series, no obvious
      size effect was apparent on tumor visibility using either imaging modality. The
      present study shows that the false-negative rate of radiological as well as
      ultrasound mammography is higher than usually perceived. Given the
      complementarity of radiological and ultrasound mammography, their combination
      proves highly sensitive and highly specific. However, this conclusion will only
      apply when both breasts are examined completely, but not when ultrasound
      examination of the breasts is restricted to the imaging of an anomaly detected
      with radiological mammography. The time needed to perform a complete breast
      examination reduces its potential use in a screening program. On the other hand,
      its use appears of major relevance in patients with breasts where the performance
      of radiological mammography is questionable, such as younger women, or women with
      dense breasts.

PMID- 12796974
TI  - Breast examinations with continuous wave and color Doppler.
AB  - Continuous wave Doppler has been used for many years to characterize malignant
      breast lesions. With continuous wave Doppler pencil probes, operating at
      frequencies between 8 and 10 MHz, 94% of the carcinomas have shown abnormal
      vascularity. Flow assessment with continuous wave Doppler alone is only possible
      in palpable lesions. We have improved the diagnostic accuracy by combining
      continuous wave Doppler and B-mode ultrasound which allows for flow detection in
      non-palpable lesions. This procedure is rather complicated, because of sound
      interference, and requires a good deal of experience. Ultrasound equipment with
      color flow mapping has been available for several years. However, during the last
      3 years, the sensitivity of the instruments has been improved, allowing the
      detection of flow in microscopic vessels which are not visible in B-mode
      scanning. Evaluation of this method is difficult, as the sensitivity of color
      Doppler equipment shows remarkable variations. In order to evaluate the
      capability of color Doppler for investigation of abnormal blood flow in breast
      malignancies, we examined 120 symptomatic women using different types of
      equipment and compared the findings to those of continuous wave Doppler. In ten
      of 44 carcinomas, no color flow signals were found. However, continuous wave
      Doppler showed low vascularity in all of these ten false-negative cases. Among
      the remaining patients with benign disease, no false-positive reports were made.
      The major difficulty in flow assessment with color Doppler was the heterogeneous
      vascularity of breast malignancies. When a low Doppler frequency (<or= 5 MHz) is
      used, signals may not be detected from poorly vascularized cancers.

PMID- 12796976
TI  - Magnetic resonance imaging in obstetrics and gynecology - essential tool or
      expensive toy?

PMID- 12796975
TI  - Prenatal diagnosis of cleft palate: contribution of color Doppler ultrasound.
AB  - The antenatal diagnosis of cleft palate by ultrasound can sometimes be difficult
      by conventional B-mode imaging, especially when the tongue is in its normal
      position. We describe two cases which illustrate the value of color Doppler in
      the antenatal diagnosis of cleft palate. In the first case, at 32 weeks'
      gestation, there was a large defect with a massive passage of flow extending from
      the buccal cavity into one of the nasal fossae. In the second case, at 22 weeks'
      gestation, a parasagittal view demonstrated the fetal tongue to be in the normal
      position, but there was an abnormal trajectory off low from the buccal cavity
      into one of the nasal fossae followed by an exit at the level of the cleft.
      Although a cleft lip was demonstrated on B-mode imaging, we would not have been
      able to make the diagnosis of cleft palate without color Doppler. This is the
      first report describing the contribution of color Doppler to the antenatal
      diagnosis of cleft palate.

PMID- 12796977
TI  - Selective termination down to a singleton pregnancy.

PMID- 12796978
TI  - Tissue characterization in obstetrics and gynecology: the present state and
      future possibilities.

PMID- 12796979
TI  - Antenatal genesis of developmental disabilities.

PMID- 12796980
TI  - Selective termination down to a singleton pregnancy.

PMID- 12796981
TI  - Relationship between fetal acidemia at cordocentesis and subsequent
      neurodevelopment.
AB  - To determine whether there is a relationship between chronic fetal acidemia and
      subsequent neurodevelopment, a follow-up study was undertaken of 36 children with
      normal karyotype and morphology, who had prenatal cordocentesis for severe growth
      retardation. The main outcome measure was the Griffiths neurodevelopmental
      quotient. The children who had acidemia as fetuses (n = 13) had a significantly
      lower developmental quotient (mean = 91.8, SD = 6.3) than those with normal (n =
      23) fetal blood pH (mean = 100.3, SD = 10.3; t = -2.68, p = 0.011). There was
      also a significant correlation between developmental quotient and the degree of
      fetal acidemia (r = 0.41, n = 36, p = 0.012). The pregnancies with acidemic
      fetuses had similar epidemiological characteristics to those with fetuses with a
      normal pH, except for a higher incidence of smoking. There was no significant
      correlation between the degree of growth retardation (birth weight expressed as
      multiples of SD from the mean for gestational age and sex) and fetal acidemia (r
      = -0.23, n = 36, NS) or subsequent Griffiths developmental quotient (r = -0.005,
      n = 36, NS). The results show an association between chronic fetal acidemia and
      subsequent impaired neurodevelopment. This observation suggests that future
      preventative interventions may be possible.

PMID- 12796982
TI  - Selective termination to a singleton pregnancy is ethically justified.
AB  - Consensus presently opposes selective termination of a multifetal pregnancy to a
      singleton. We reject this consensus because the arguments made in defense of it
      are deficient. We show that these arguments rely on the indefensible assumption
      that the previable fetus possesses independent moral status. We conclude that,
      since selective termination of a multifetal pregnancy of any order to a singleton
      is ethically justifiable, a pregnant woman's request for selective termination to
      a singleton from twins or a higher-order multiple gestation should be respected
      and implemented. Physicians who object to selective termination to a singleton in
      private conscience should not feel compelled to perform the procedure but are
      obligated to make an appropriate referral.

PMID- 12796983
TI  - Prenatal diagnosis of lobar holoprosencephaly.
AB  - Lobar holoprosencephaly was identified with sonography in 12 fetuses between 21
      and 35 weeks' gestation. A confident diagnosis was made in each case by a mid
      coronal view of the brain demonstrating absence of the cavum septum pellucidum
      with fusion and squaring of the frontal horns. The only associated anomaly was
      Dandy-Walker malformation that occurred in three cases. All fetuses had mild to
      severe ventriculomegaly. Five pregnancies were terminated; there was one
      spontaneous abortion and six fetuses were delivered at term. A ventriculo
      peritoneal shunt was implanted in four. Follow-up was available for five and
      revealed severe mental retardation in each case. Lobar holoprosencephaly is
      amenable to prenatal ultrasound diagnosis, although a differentiation with other
      cerebral malformations may be difficult at times. The outcome of affected infants
      remains uncertain, but neurological impairment occurs frequently.

PMID- 12796984
TI  - Prenatal ultrasound semiography of anencephaly: sonographic-pathological
      correlations.
AB  - A better understanding of the ultrasound findings in each of the different types
      of fetal anencephaly can help to reduce the number of false-negative diagnoses of
      this condition during the prenatal period. Errors in the estimation of the
      remaining cerebral tissue (angiomatous stroma, area cerebrovasculosa) can cause
      false-negative diagnoses or diagnostic confusion with cases of microcephaly or
      incomplete ossification of the cranial vault. In a retrospective study, 30
      fetuses with anencephaly (diagnosed at 13-38 weeks of gestation) were grouped, in
      terms of their ultrasound results, according to the Nanagas classification. The
      ultrasound diagnoses were then correlated with those found through autopsy, to
      identify any errors in the ultrasound classification.

PMID- 12796985
TI  - The impact of alpha-adrenergic stimulation on umbilical blood flow.
AB  - This study evaluated the effects of intranasal phenylephrine, an alpha-adrenergic
      agonist used for respiratory congestion, on uteroplacental blood flow. Twelve
      subjects were recruited from the Women's Clinic. Inclusion criteria were age
      greater than 18 years, singleton gestation, absence of medical illness and
      gestational age of 22-38 weeks. Phenylephrine (0.2 ml of 1% aq. solution) was
      applied to each nostril. Maternal blood pressure and pulse, umbilical artery
      velocimetry, and fetal heart rate were recorded prior to drug administration and
      at 5, 15, 30, 45 and 60 min after administration. There were no significant
      changes in maternal pulse, blood pressure or fetal heart rate. All subjects had
      normal baseline umbilical artery Doppler systolic/diastolic ratios. Eleven of 12
      subjects demonstrated an elevation of the systolic/diastolic ratio consistent
      with vasoconstriction following administration. This elevation reached
      statistical significance at 30 min. Significant individual variation existed with
      regards to timing of maximal excursion of the systolic/diastolic ratio. The mean
      maximal change of the systolic/diastolic ratio was 1.57 +/- 1.25 (p < 0.001)
      ranging from -0.53 to 4.11. The use of over-the-counter alpha-adrenergic agents
      may result in decreased umbilical artery flow velocities. In high-risk
      pregnancies these medications may be contraindicated.

PMID- 12796986
TI  - Indomethacin and amniocentesis-induced changes in fetal flow velocity waveforms.
AB  - The effect of genetic amniocentesis on flow velocity waveforms in the fetal aorta
      and the umbilical artery, and fetal heart rate and their correlation with uterine
      contractions was examined in 75 pregnant women who underwent this procedure.
      Forty-three were untreated and 32 were pretreated with indomethacin. Median
      maternal age was 36 years and median gestational age was 18 weeks. The resistance
      index of waveforms from the fetal aorta was stable at 0.8 throughout the
      approximately 20-h study period in both groups, but the systolic/diastolic ratio
      in the umbilical artery increased significantly after amniocentesis in the
      untreated group, and remained stable in the treated group. Fetal heart rate
      remained at about 150 beats/min throughout all measurements in both groups. These
      findings indicate that genetic amniocentesis causes an increase in downstream
      resistance in the umbilical artery which, however, remains within normal limits.
      This mild fetoplacental response to amniocentesis can be suppressed by the
      administration of a potent prostaglandin inhibitor like indomethacin.

PMID- 12796987
TI  - Vanishing twins: the frequency of spontaneous fetal reduction of a twin
      pregnancy.
AB  - This study examines the outcome of 126 twin pregnancies diagnosed by ultrasound
      examination at 6-16 weeks' gestation. Fifty-nine patients conceived by in vitro
      fertilization (IVF) and embryo transfer and had a routine scan. The 67 non-IVF
      pregnancies had a scan for other clinical indications including threatened
      abortion. When live twins were detected prior to 7 weeks'gestation, only 71% of
      pregnancies resulted in live twin neonates. Each fetus of a multiple pregnancy
      had a 19% chance of dying in utero or in the neonatal period of diagnosed prior
      to 7 weeks, and 11% if both were found to be alive between 7 and 10 weeks. The
      fetal loss rate was similar for IVF and non-IVF pregnancies.

PMID- 12796988
TI  - Accuracy of transvaginal ultrasound and serum hCG in the diagnosis of ectopic
      pregnancy.
AB  - Transvaginal ultrasound was performed upon admission of 127 patients with a
      clinical suspicion of ectopic pregnancy in association with human chorionic
      gonadotropin (hCG) determination. Failure to visualize with sonography an
      intrauterine gestational sac with an hCG level superior to 1000 mIU/ml identified
      25/42 tubal pregnancies with a positive predictive value of 86% and a specificity
      of 93%. Abnormal adnexal findings occurred in 95% of the ectopic pregnancies.
      Extrauterine gestational sacs with or without embryos could be confidently
      detected in 19 ectopic pregnancies (45%). A complex adnexal mass was seen in 19
      cases and yielded a positive predictive value of 90% (19/21). Adnexal gestational
      sacs and complex masses were seen more frequently in those ectopic pregnancies
      with an hCG level above 1000 mIU/ml but the difference was not significant (100%
      versus 78%). Simple adnexal cysts were found more frequently in intrauterine
      pregnancies, and fluid in the cul-de-sac was also not indicative of ectopic
      pregnancy (positive predictive value, 29%). Transvaginal ultrasound has a primary
      role in the diagnosis of ectopic pregnancy. The combined use of uterine and
      adnexal sonography associated with elevated hCG levels allows a definitive
      diagnosis in the vast majority of cases at a very early stage, when the chances
      for a successful conservative treatment are greater.

PMID- 12796989
TI  - The assessment of bladder neck movement in postpartum women using perineal
      ultrasonography.
AB  - Twenty-three postpartum women underwent perineal ultrasonography to determine
      bladder neck position at rest, on Valsalva and during pelvic floor contraction.
      On Valsalva, significant descent of the bladder neck and apposition to the
      symphysis pubis occurred. During pelvic floor contraction, there was significant
      elevation of the bladder neck; however, in approximately one-third of cases no
      movement was demonstrated. The bladder neck was shown to move through the arc of
      a circle whose center is the inferior border of the symphysis pubis. Perineal
      ultrasound provides a simple, objective way of measuring bladder neck elevation
      during pelvic floor contraction. This may be a more appropriate means of
      determining treatment outcome, in women undergoing conservative treatment for
      genuine stress incontinence, than measures of vaginal squeeze pressure.

PMID- 12796990
TI  - The role of ultrasound in gynecological emergencies.
AB  - The expanding use of ultrasonography in gynecology puts increasing strain on the
      resources of ultrasound departments; any mechanism to increase the diagnostic
      efficiency of the scan and reduce unwarranted investigation would, therefore, be
      welcome. This prospective study examines the use of abdominal ultrasound
      examination in gynecological emergencies over a 6-month period in a London
      teaching hospital. The examination changed the clinical management in 33% of
      cases where the pregnancy test was positive, but in only 14% where it was
      negative. In the former group, the confirmation of viable intrauterine pregnancy
      reassured both patient and clinician in 84% of the cases, making the test a
      useful investigation in 89% of the total cases where the pregnancy test was
      positive. When the pregnancy test was negative, the ultrasound scan was more
      likely to be useful if requested by doctors with gynecological experience. In
      cases of incomplete spontaneous abortion, ultrasound was not found to be a useful
      investigation. Access to ultrasound equipment by, and basic ultrasound training
      of admitting junior doctors with gynecological experience would reduce referrals
      to the ultrasound department and reduce admissions to hospital, whilst improving
      appreciation of the role of ultrasound in gynecological emergencies.

PMID- 12796991
TI  - First-trimester diagnosis of cystic hygromata by transvaginal sonography.
AB  - This paper reports two cases of fetal nuchal cystic hygromata diagnosed in the
      first trimester of pregnancy by transvaginal sonography. In the first case, at 10
      weeks' gestation, in addition to the hygromata, the fetus had an exomphalos. In
      the second case, at 13 weeks' gestation, the fetus had hydrocephalus and pleural
      effusion. Transabdominal chorion villus sampling was carried out and the fetal
      karyotypes were trisomy 18 and trisomy 21, respectively.

PMID- 12796992
TI  - Early prenatal diagnosis of type III bilateral congenital cystic adenomatoid
      malformation of the lung.
AB  - We present a case of type III fetal cystic adenomatoid malformation with
      bilateral total involvement of the lungs. The characteristic sonographic findings
      are echogenic homogeneous lung mass, fetal ascites and placentomegaly. The early
      diagnosis at 16 weeks' gestation allows the elective termination of pregnancy
      because of the likely fatal prognosis. To our knowledge, this is the earliest
      reported case of congenital cystic adenomatoid malformation of the lung that has
      been detected prenatally.

PMID- 12796993
TI  - Early prenatal diagnosis of type II cystic adenomatoid malformation of the lung:
      sonographic and histological findings.
AB  - Cystic adenomatoid malformation is a rare abnormality of the fetal lung.
      Depending on the size and histology of the cyst, it is classified as type I, II
      or III. With improving ultrasound technology, prenatal diagnosis during the mid
      trimester is now possible; however, the earliest previous reports of type II
      cases have been at 23-24 weeks' gestation. We here report cases diagnosed at 19.5
      and 20.5 weeks. In contrast to the appearance of multiple small cysts seen later
      in pregnancy, these cases showed a predominance of marked hyperechogenicity,
      usually associated with type III malformations, with small areas of lung involved
      by sonographically detectable cysts. Both families chose pregnancy termination.
      Sonographic findings, counselling, and histology are presented and discussed.

PMID- 12796995
TI  - A good start.

PMID- 12796994
TI  - Biophysical assessment of the fetus.

PMID- 12796996
TI  - Transvaginal sonography in endometrial cancer.

PMID- 12796997
TI  - Abnormal fetal movements.

PMID- 12796998
TI  - Genetic amniocentesis in twin pregnancies: results of a multicenter study of 529
      cases.
AB  - To evaluate the risk of abortion after genetic amniocentesis in twin pregnancies,
      a retrospective study of 15 centers was performed. The spontaneous abortion rate
      up to 20 completed weeks of gestation was 2.3%; the abortion rate up to 28
      completed weeks, as defined by WHO, was 3.7%. The abortion rate could not be
      correlated either with the number of needle insertions or with the type of marker
      dye used. There was also no correlation between the abortion rate and the
      gestational age at which amniocentesis was performed. A significant association
      was shown between congenital intestinal obstructions and the application of
      methylene blue intra-amniotically as a marker dye. Considering the increased
      natural loss rate in multiple gestations, amniocentesis in twin pregnancies seems
      to be a safe and reliable technique.

PMID- 12796999
TI  - Sonographic indications for karyotyping procedures. An international
      questionnaire.
AB  - An international survey was conducted to investigate attitudes to karyotyping
      procedures in cases of fetal anomalies detected by ultrasound. A questionnaire
      was sent to 111 current members of the International Society of Ultrasound in
      Obstetrics and Gynecology. The overall response rate was 48%. Analysis of the
      replies reflects a wide variation in the criteria for the definition of a
      sonographic abnormality, the indication for a diagnostic procedure, and the
      timing for intervention. The results emphasize the need for additional data on
      several sonographic findings (e.g. choroid plexus cysts, renal pyelectasis, short
      limbs) and for improved selection of patients for chromosomal investigation.

PMID- 12797000
TI  - Erythroblastosis in birth asphyxia.
AB  - The pH and erythroblast count in umbilical venous blood were measured in 27 term
      neonates with normal birth weights. In seven cases, infants were admitted to the
      neonatal intensive care unit because of birth asphyxia, and the findings in these
      cases were compared to the values of the 20 non-asphyxiated neonates that were
      delivered either vaginally (n = 10) or by elective Cesarean section (n = 10). The
      umbilical venous blood pH in the asphyxiated group was significantly lower than
      that in the control group of infants that were delivered by Cesarean section, but
      not significantly different from the controls that were delivered vaginally. In
      contrast, the erythroblast count in the asphyxiated group was significantly
      higher than that in the controls, irrespective of the mode of delivery. These
      findings suggest that cord blood erythroblast count at delivery may provide a
      better measure of fetal tissue hypoxia than umbilical venous pH.

PMID- 12797001
TI  - Relationship between umbilical and fetal cerebral blood flow velocity waveforms
      and umbilical venous blood gases.
AB  - Nineteen women (mean +/- SD: 28 +/- 5 years) with small fetuses relative to
      gestational age (mean +/- SD: 32 +/- 2.2 weeks of gestation) were referred to our
      unit for cordocentesis for the determination of fetal karyotyping. Four of these
      19 patients had small-for-gestational-age ultrasound-derived measurements under
      the third centile for gestational age. Fetal blood gases were measured in the
      umbilical vein. Umbilical artery and fetal internal carotid artery Doppler
      examinations were performed 15 min before cordocentesis. The results showed a
      progressive and proportional increase in umbilical artery resistance index with
      hypoxia (p < 0.001), hypercapnia (p < 0.025) and acidosis (p < 0.005). Moreover,
      the results showed a progressive and proportional decrease in fetal internal
      carotid artery resistance index with hypoxia (p < 0.01), hypercapnia (p < 0.01)
      and acidosis (p < 0.025). Fetal blood gases are therefore related to umbilical
      circulatory function and cerebral vasodilatation, suggesting fetal vascular
      redistribution.

PMID- 12797002
TI  - Ultrasound diagnosis of fetal macrosomia.
AB  - Macrosomic infants and their mothers are at increased risk for intrapartum injury
      and perinatal morbidity and mortality. This study investigates the effectiveness
      of individual ultrasound fetal measurements, ponderal indices and estimated fetal
      weight in the identification of macrosomia in 732 pregnant patients who underwent
      ultrasound examination within 7 days of delivery. All the indices evaluated were
      compared for accuracy in predicting birth weight. Statistical comparison revealed
      that estimated fetal weight predicted macrosomia better than single ultrasound
      parameters and ponderal indices. The formulae tested yielded an accuracy of 94%
      and a positive predictive value of 90%. Abdominal diameter and abdominal
      circumference values above the 90th centile correctly predicted macrosomia in 82%
      and 72% of cases, respectively. Fetal length showed a sensitivity of 61% with a
      predictive positive test of 41%. Femur length-to-abdominal circumference ratio
      detected macrosomia with a sensitivity of 80% and an accuracy of 82%. The other
      single ultrasound parameters and ponderal indices were significantly less
      indicative of macrosomia. The combined use of four indices (growth profile) did
      not improve the effectiveness of ultrasound in detecting fetal macrosomia. We
      conclude that the optimal prediction of fetal macrosomia is obtained from
      mathematical formulae for fetal weight estimation, based on several fetal
      measurement parameters and adjusted for different gestational periods.

PMID- 12797003
TI  - The ultrasonic assessment of discordant growth in twin pregnancies.
AB  - Discordant fetal growth, as defined by an intertwin weight difference (calculated
      as a percentage of the weight of the larger twin) of 20% or more, is associated
      with an increased perinatal mortality and morbidity. In this study, the accuracy
      of ultrasound estimation of fetal weight by abdominal circumference and
      biparietal diameter measurements in 107 twin pregnancies was assessed. Discordant
      growth greater than 20% as measured by ultrasound was found to have a sensitivity
      of 5-25%, a specificity of 87-95%, a positive predictive value of 12-43% and a
      negative predictive value of 80-85% at gestations ranging from 28 weeks to term.
      ROC calculations showed that changes in the discordance level used did not
      improve the value of the test. These results indicate that ultrasound measurement
      of fetal weight alone cannot be used accurately to assess discordant growth in
      twin pregnancies.

PMID- 12797004
TI  - The use of endovaginal ultrasound to diagnose invasion of endometrial carcinoma.
AB  - Endovaginal ultrasound was used in 30 women to characterize endometrial carcinoma
      with respect to myometrial invasion according to FIGO recommendations for
      surgical staging of endometrial cancer. The ultrasound data were correlated to
      macroscopic findings of the uterine specimen and to histopathology. Using
      endovaginal ultrasound, the sensitivity of detecting myometrial invasion of > 50%
      was 15/19 or 79%. However, the positive predictive value was 100%, in all cases
      when ultrasound suggested myometrial invasion of > 50%. This was confirmed on
      histopathological examination of the tumor specimen. Cervical tumor extension was
      correctly diagnosed in all six women in which it was present. Endovaginal
      ultrasound seems to be a reliable method of assessing tumor invasion and
      engagement of the cervix. This non-invasive method could be included as an
      important tool in the establishment of individualized treatment programs in women
      with endometrial carcinoma.

PMID- 12797005
TI  - Depth of myometrial invasion in endometrial cancer: preoperative assessment by
      transvaginal ultrasonography and magnetic resonance imaging.
AB  - Depth of myometrial invasion in endometrial cancer correlates with pelvic lymph
      node metastases and tumor recurrence. Thirty patients diagnosed as having FIGO
      stage I endometrial carcinoma on the basis of D&C were evaluated preoperatively
      by magnetic resonance imaging (MRI); 14 cases of the same group were also
      evaluated by transvaginal ultrasound. The degree of invasion evaluated by MRI and
      transvaginal sonography was compared to the pathological specimens. MRI was
      successful in evaluating myometrial invasion in 2.5 of 30 cases (accuracy 83%,
      sensitivity 87%, specificity 78%, positive predictive value 82%, negative
      predictive value 84%). Evaluation with transvaginal sonography was accurate in 11
      of 14 cases (accuracy 78%, sensitivity 80% specificity 77%, positive predictive
      value 87%, negative predictive value 66%).

PMID- 12797006
TI  - Absence of fetal breathing and abnormal fetal behavior in prolonged preterm
      ruptured membranes: case report.
AB  - A case is described where prolonged serial observations were carried out on a
      fetus, between 26 and 3.5 weeks' gestation, the membranes having been ruptured
      from 23 weeks. No fetal breathing or cyclical activity was observed, and there
      was no evidence of development of linkage between the fetal behavioral state
      variables. This was not associated with respiratory morbidity in the neonatal
      period, but subsequently with severe developmental delay, microcephaly, myoclonic
      epilepsy and hearing impairment. Absence of fetal breathing may be a more
      important predictor of prenatal neurological abnormality than of respiratory
      morbidity following birth.

PMID- 12797007
TI  - Trisomy 18: behavioral and structural abnormalities. An ultrasonographic case
      study.
AB  - A behavioral and structural analysis using ultrasound of a fetus suffering from
      Edwards syndrome is described. A number of structural anomalies were observed:
      the classic hand deformity, extended legs, diamond-shaped head, open mouth and a
      severe cardiac abnormality. A number of distinctive behavior patterns were
      observed: vertical eye movements, longitudinal rotation of the trunk, rotation of
      hands, tremor of extremities and pulsatile body movements, which are not usually
      seen in the normal fetus. The use of behavioral indicators in the diagnosis of
      abnormalities is discussed. We conclude that the analysis of behavior may make a
      significant contribution to the ultrasonographic diagnosis of handicap.

PMID- 12797008
TI  - In utero early suspicion of superfetation by ultrasound examination: a case
      report.
AB  - We report the case of a dichorionic and diamniotic pregnancy with the unique
      feature of an early ultrasound diagnosis of a 4-week size difference, which
      persisted throughout pregnancy. At birth, the twins had a 1-month difference in
      physical and neurological maturity. We believe that only the phenomenon of a
      superfetation can explain this difference. We report the cases found in the
      literature.

PMID- 12797009
TI  - Prenatal diagnosis of an intra-abdominal ectasia of the umbilical vein with color
      Doppler ultrasonography.
AB  - A cystic lesion in the anterior upper part of the abdomen was detected in utero
      by ultrasonography. Color and pulsed Doppler studies performed over the mass
      revealed a marked turbulent flow through the cystic lesion in connection with the
      umbilical vein, suggesting the existence of an intra-abdominal ectasia of the
      umbilical vein.

PMID- 12797010
TI  - Cord vessel compression by an expanding allantoic cyst: case report.
AB  - The umbilical cord has been inadequately studied by ultrasound. Umbilical cord
      masses are rare and often misdiagnosed.A case of a 4.3 x 3.2 cm anechoic floating
      cystic umbilical mass is reported. Doppler examination of the cord proximal to
      the cyst revealed a high resistance index of 0.84. Twelve hours later the cyst
      was larger (5.0 x 4.5 cm) and appeared tense; Doppler velocimetry worsened and
      absence of end-diastolic flow in the umbilical artery was found. Cardiotocography
      a few hours later showed a bradycardiac non-reactive trace with late
      decelerations. A live male weighing 1980 g was delivered by Cesarean section. At
      birth the cord position was normal. Pathological examination showed the lesion to
      be consistent with an allantoic cyst. This is the first case in which antenatal
      evidence of cord compression by an expanding allantoic cyst has been
      demonstrated.

PMID- 12797011
TI  - Retention of fetal bones 8 years following termination of pregnancy.
AB  - We report on an unusual case where bone had been retained in the endometrium for
      a period of 8 years following termination, causing no symptoms except
      subfertility. Routine ultrasonography diagnosed the foreign body and this was
      removed by hysteroscopy assisted by ultrasound scanning. Pregnancy resulted after
      6 months. A review of the literature is presented.

PMID- 12797012
TI  - Prenatal karyotyping: when, how and whom?

PMID- 12797013
TI  - Transvaginal color Doppler in gynecology.

PMID- 12797014
TI  - Transvaginal color Doppler and ovarian tumors.

PMID- 12797017
TI  - Three-dimensional ultrasound imaging in patient diagnosis and management: the
      future.

PMID- 12797016
TI  - Training in obstetrical and gynecological ultrasound: an Australian viewpoint.

PMID- 12797018
TI  - Amniotic fluid volume - does it really help us?

PMID- 12797019
TI  - Three-dimensional imaging of solid breast tumors with ultrasound: preliminary
      data and analysis of its possible contribution to the understanding of the
      standard two-dimensional sonographic images.
AB  - Reconstructed three-dimensional sonographic images are presented from patients
      having different histological types of breast tumors. Scanning is manual and
      performed using two-dimensional annular array, sector transducers fitted on a
      mechanical arm, to provide spatial location. The three-dimensional data are
      displayed using two different modalities. Planar reformatted sections allow the
      visualization of planes reconstructed along any direction chosen by the operator.
      Of particular interest are the reconstructions obtained along equatorial planes
      of the tumors, i.e. planes parallel to the chest wall and, consequently, to the
      fibroglandular layer of the breast. Volume rendering is obtained using the shaded
      surface visualization technique.Three-dimensional imaging provides new
      information and allows a better interpretation of the standard two-dimensional
      images. Planar reformatted sections confirm that ductal carcinomas present margin
      jagging on all views, including the equatorial section planes. Using the shaded
      surface visualization technique, these tumors appear with a spiked outer surface.
      Thus, the most specific sonographic finding associated with ductal carcinomas may
      be that margin jagging extends over the entire periphery of the mass. On planar
      reformatted sections, benign tumors are surrounded by a continuous hyperechogenic
      rim, i.e. the rim is present irrespective of the section plane orientation.
      Medullary carcinomas are also surrounded by a hyperechogenic rim. However, a
      clearly distinctive feature of these lesions is found on planar reformatted
      sections: the rim is discontinuous on certain section planes. A mass can be
      considered benign only if its rim is continuous, i.e. if it is present all around
      the tumor.

PMID- 12797020
TI  - Doppler studies of the uteroplacental circulation in pregnancies complicated by
      diabetes.
AB  - The aim of this study was to evaluate the uteroplacental side of the circulation
      in pregnancies complicated by diabetes. A total of 54 women with pregnancies
      complicated by diabetes underwent uterine and umbilical artery Doppler studies.
      Uterine Doppler velocity waveforms were not obtained in two women. The prevalence
      of abnormal uterine artery velocity waveforms was much higher than in a non
      diabetic population (15.4% vs. 2%, p < 0.001). Those eight women with abnormal
      uterine Doppler studies had a statistically higher incidence of poor glycemic
      control, chronic hypertension, polyhydramnios, vasculopathy, pre-eclampsia,
      Cesarean births for fetal distress and newborns with respiratory distress
      syndrome. In this group of patients, the umbilical circulation was not considered
      to be a contributing factor in the development of problems.

PMID- 12797021
TI  - The use of fetal echocardiography for predicting intrapartum fetal heart rate
      patterns in the post-term pregnancy.
AB  - One of the shortcomings of antepartum testing in the post-term pregnancy is that
      it does not identify the majority of fetuses who develop abnormal intrapartum
      fetal heart rate changes. The purpose of this study was to determine whether
      antenatal cardiovascular evaluation could aid in the identification of post-term
      fetuses at risk for intrapartum heart rate abnormalities. Seventy-five patients
      with a gestational age greater than 41 weeks underwent a non-stress test,
      amniotic fluid index and real-time assessment of the heart for the presence or
      absence of a pericardial effusion. M-mode measurements of the right ventricular
      inner dimension (RVID), left ventricular inner dimension (LVID), biventricular
      outer dimension (BVOD) and Doppler velocimetry of the umbilical artery (S/D) were
      performed. Group I (n = 32) had normal intrapartum heart rate tracings. Group II
      (n = 20) had abnormal intrapartum fetal heart rate tracings but did not undergo
      emergency delivery. Group III (n = 23) had abnormal intrapartum fetal heart rate
      tracings but underwent emergency delivery. When comparing Group I with Group II,
      the latter had significant differences for abnormal RVID, RVID/LVID ratio, and
      pericardial effusion. When comparing Groups I and III, there were significant
      differences for RVID, RVID/LVID ratio, pericardial effusion, BVOD, LVID and
      amniotic fluid index. Neither the non-stress test nor S/D predicted abnormal
      intrapartum fetal heart rate patterns. For prediction of abnormal intrapartum
      heart rate patterns, the sensitivities of the RVID (0.79), LVID (0.33), RVID/LVID
      ratio (0.72) and BVOD (0.63) were 1.7-4 times greater than the non-stress test
      (0.19) and the sensitivities of the RVID, RVID/LVID ratio and BVOD were 2 times
      greater than the amniotic fluid index (0.28). The positive (0.50-0.86) and
      negative (0.42-0.68) predictive values were similar for all groups. To predict
      emergency delivery associated with abnormal heart rate tracings, the
      sensitivities of the RVID (0.83), RVID/LVID ratio (0.70) and BVOD (0.65) were 2.5
      3 times greater than the non-stress test (0.26) and 1.5 times greater than the
      amniotic fluid index (0.39). The positive (0.36-0.56) and negative (0.70-0.86)
      predictive values were similar. The presence of pericardial effusion had a higher
      sensitivity than the non-stress test and amniotic fluid index for predicting
      abnormal intrapartum heart rate patterns but not emergency delivery. Doppler
      velocimetry of the umbilical artery had a lower sensitivity than the non-stress
      test and amniotic fluid index for predicting intrapartum heart rate patterns as
      well as identifying the fetus needing emergency delivery. The results of this
      study would suggest that there is initially dilatation of the right ventricle
      which may be associated with abnormal intrapartum fetal heart rate patterns.
      However, when the left ventricle dilates, leading to cardiomegaly, there is a
      greater incidence of abnormal intrapartum fetal heart rate changes and associated
      emergency delivery. The amniotic fluid index appears to be a later finding for
      predicting abnormal intrapartum fetal heart rate changes.

PMID- 12797022
TI  - Ultrasound assessment of amniotic fluid volume: a comparison of the single
      deepest pool and amniotic fluid index to predict perinatal morbidity.
AB  - The ability of the amniotic fluid index and the single deepest pool to predict
      perinatal morbidity was compared in 291 high-risk singleton pregnancies without
      ruptured membranes or fetal renal abnormalities. A poor outcome was defined as a
      birth weight < -2 standard deviations, emergency Cesarean section for fetal heart
      rate abnormalities in labor, 5-minute Apgar score < 7, umbilical venous pH at
      delivery < 7.15 and admission to the special care baby unit. At least one of
      these parameters occurred in 71 (24%) of the 291 pregnancies. Oligohydramnios (an
      amniotic fluid index <or= 5 cm) occurred in 19 (6.5%) of the 291 pregnancies;
      this group was more likely to have a poor outcome than those with an amniotic
      fluid index > 5 cm (chi(2) = 2.41, p = 0.02). There was a significant correlation
      between amniotic fluid index and single deepest pool measurements (r = 0.83, n =
      291, p < 0.0001). At the recommended cut-off values, the single deepest pool and
      the amniotic fluid index had sensitivities of 7% and 13%, respectively and
      specificities of 96% and 95% for predicting perinatal morbidity. Receiver
      operating characteristic curve analysis showed that these poor results were not
      the result of the cut-off values chosen and that the performances of the amniotic
      fluid index and single deepest pool were similar.

PMID- 12797023
TI  - Biparietal diameter and femur length discrepancies: are maternal characteristics
      important?
AB  - We examined whether gestational age, maternal race or height can be used to
      explain discrepancies between biparietal diameter- and femur length-derived
      gestational ages by analyzing ultrasound scans from 8041 consecutively scanned,
      singleton pregnancies, using multiple regression analysis. While a consistent
      association was noted between differences of more than 3 weeks and less than 3
      weeks and advancing gestational age, neither maternal height nor race were
      significantly related. We conclude that, first, discrepancies between gestational
      age by biparietal diameter and femur length are rare (5%) and, second, the
      presence of discrepancies should not be dismissed on the basis of maternal
      stature or race and should alert the clinician to possible abnormal fetal growth
      or development.

PMID- 12797024
TI  - Fetal renal artery blood velocimetry in multicystic kidney disease.
AB  - Color flow mapping and Doppler velocimetry were used to measure impedance to flow
      in both renal arteries of 11 fetuses with unilateral multicystic kidney disease
      at 19-34 (mean = 26) weeks' gestation. In all cases, the pulsatility index in the
      renal artery of the multicystic kidney was higher than that of the contralateral
      normal kidney; the mean pulsatility index in the arteries of the affected kidneys
      was significantly higher than the normal mean for gestation.

PMID- 12797025
TI  - Fetal hydronephrosis and renal artery blood velocity.
AB  - The renal artery blood velocity waveform was recorded by Doppler ultrasound in 17
      fetuses with hydronephrosis in the third trimester of pregnancy. The waveform was
      analyzed for pulsatility index and related to the degree of dilatation of the
      renal pelvis. The pulsatility index was found to be above the renal reference
      range in only five out of the total of 31 kidneys examined. No relationship was
      found between the degree of dilatation and pulsatility index. A slight
      relationship was, however, found between abnormal pulsatility index and the need
      for operative intervention in the neonatal period. Doppler ultrasound is a
      valuable tool for evaluating renal circulation, but the results suggest limited
      clinical value in fetuses with hydronephrosis.

PMID- 12797026
TI  - Transvaginal sonography of the uterine cavity following curettage for early
      pregnancy failure.
AB  - In a study of 50 women presenting with sonographically confirmed early pregnancy
      failure, the uterine contents were measured in both sagittal and transverse
      planes before proceeding with evacuation of the retained products of conception.
      A repeat sonographic study of the empty uterine cavity was performed on the day
      after curettage and similar measurements were made, the subjects having been
      divided into four groups according to gestational age. There was no significant
      difference between the groups in the postoperative measurements of either uterine
      cavity width or area, nor was the size of the empty uterine cavity influenced by
      the volume of tissue within the uterus before evacuation. Whilst the measurement
      of width was similar both before and after evacuation of the uterus in all
      groups, the sagittal area was significantly smaller postoperatively. There was no
      evidence of retained tissue at any of the postoperative sonographic examinations,
      nor did any of the subjects in the study develop subsequent complications.
      Assuming the dimensions of the uterine cavity following curettage are
      representative of an empty uterus, this will form the basis of a prospective
      study to determine whether spontaneous abortion can be safely managed without
      curettage in selected cases, if the preoperative sonographic measurements fall
      within a specified range.

PMID- 12797027
TI  - Paracetamol-associated luteinized unruptured follicle syndrome: effect on
      intrafollicular blood flow.
AB  - We are using transvaginal ultrasonography with color Doppler imaging to study
      changes in intrafollicular blood flow over the periovulatory period. We report
      here the findings from one volunteer (subject 9), who took two tablets of
      paracetamol (1000 mg) twice daily (between 07.00 and 08.00, and 18.00 and 19.00)
      for 2 consecutive menstrual cycle days (12 and 13) to alleviate a headache, which
      was shown retrospectively to have occurred within the duration of the luteinizing
      hormone (LH) surge in peripheral plasma. The drug appeared to have a profound
      effect on peak systolic blood velocity within the preovulatory follicle. Color
      (an index of blood velocity) disappeared and flow velocity waveforms were not
      detectable for at least 4 h. Color then re-appeared, but the peak systolic blood
      velocity had reduced by 69.8% (from 18.2 to 5.5 cm/s). The peak systolic blood
      velocity recovered subsequently to 16.3 cm/s, but the follicle did not rupture
      and continued to grow to a maximum diameter > 59 mm. There was no apparent effect
      of the drug on expected changes in the circulating levels of estradiol, LH,
      follicle stimulating hormone or progesterone. The secretory phase of the
      menstrual cycle lasted 13 days (i. e. day of LH peak to day of next menses minus
      one). We suggest that paracetamol taken at the time of the LH surge may affect
      intrafollicular peak systolic blood velocity and might inhibit ovulation.
      Possible molecular mechanisms are discussed.

PMID- 12797028
TI  - Spontaneous remission of urinary tract obstruction and ascites in a fetus with
      posterior urethral valves.
AB  - We report a case of posterior urethral valves with its typical sonographic
      findings. The initial diagnosis of an infravesical obstruction was made at 18
      weeks gestation based on the finding of an enlarged fetal bladder and bilateral
      dilated renal pelves. Weekly observations showed no change in bladder size until
      27 weeks gestation. At this time there was a significant increase in dilatation,
      the bladder wall was thickened and at 28 weeks a large amount of fetal ascites
      was diagnosed, but there was no oligohydramnios. Fetal urine investigations
      following ultrasound-guided puncture of the fetal bladder revealed hypotonic
      urine and adequate renal function. Hence no vesicoamniotic drainage was
      performed. At 32 weeks, spontaneous remission of ascites and reduction of the
      bladder dilatation were noted. The fetus was delivered vaginally at term. Follow
      up of the newborn during the 1st year of life is reported. At the age of 1 year
      the infant shows good renal function with a serum creatinine of 0.33 mg/dl. This
      case shows that spontaneous remission of fetal urinary tract obstruction as a
      consequence of posterior urethral valves is possible. The sequence of events
      leading to spontaneous remission and the favorable outcome is discussed.

PMID- 12797029
TI  - Prenatal sonographic diagnosis and perinatal management of ectopia cordis.
AB  - Ectopia cordis is a rare malformation presenting as an isolated lesion or as part
      of the Cantrell's pentology syndrome. Prenatal ultrasonographic diagnosis of
      ectopia cordis must be followed by a careful search for associated anomalies,
      since the prognosis may vary accordingly. A case of prenatal diagnosis of ectopia
      cordis in the early second trimester is presented. Routine sonographic
      examination at 18 weeks of gestation revealed protrusion of the heart into the
      amniotic fluid, ventricular septal defect and omphalocele. The perinatal
      evaluation and management are discussed.

PMID- 12797030
TI  - In vivo investigations of the anatomy and the physiology of early human placental
      circulations.

PMID- 12797031
TI  - The fetus as a patient: the fetus as a person?

PMID- 12797032
TI  - Non-immune hydrops fetalis.

PMID- 12797033
TI  - Maternal hyperoxygenation: therapy or test in growth-retarded fetuses?

PMID- 12797036
TI  - Amnifiltration in the first trimester: feasibility, technical aspects and
      cytological outcome.
AB  - An amnifiltration system has been developed which allows collection of cells from
      the amniotic sac in the first trimester of pregnancy whilst only removing 1 ml of
      amniotic fluid in total. The cells can be cultured and harvested, using the same
      methods as early amniocentesis, to enable prenatal diagnosis of fetal karyotype.
      A range of filters constructed from different materials and of differing pore
      sizes were examined for their ability to trap and subsequently release a maximum
      number of amniotic fluid cells. The best filter membrane was found to be a
      cellulose acetate filter of 0.8 micro m pore size. To achieve the same
      cytogenetic outcome as a 10 ml amniocentesis, a minimum of 20 ml amniotic fluid
      must be filtered and recirculated through the system.

PMID- 12797035
TI  - Foramen ovale size in the normal and abnormal human fetal heart: an indicator of
      transatrial flow physiology.
AB  - We used fetal echocardiography to measure the sizes of the foramen ovale and
      atrial septum in 80 human fetuses from 17.5 to 38 weeks gestation. Forty-six
      fetuses had normal cardiac anatomy, 19 had left heart obstructive lesions, and 15
      had right heart obstructive lesions. Pulsed and color flow Doppler studies were
      incorporated when available. We found that normal fetuses had a foramen
      ovale/atrial septum size ratio of 0.33 +/- 0.04 (mean +/- SD). In all (52%)
      fetuses in which it was available, pulsed Doppler study revealed bidirectional,
      but predominantly right-to-left, flow through the foramen ovale. Fetuses with
      left heart obstructive lesions had a foramen ovale/atrial septum size ratio
      smaller than normal (0.28 +/- 0.05; p < 0.001). Seven of nine fetuses with left
      heart obstructive lesions who had color Doppler studies demonstrated reversal of
      the normal flow pattern, exhibiting unidirectional left-to-right transforamenal
      flow. Those with right heart obstructive lesions had a larger than normal foramen
      ovale/atrial septum size ratio (0.47 +/- 0.04; p < 0.001). Nine fetuses with
      right heart obstructive lesions had color Doppler studies which demonstrated
      almost exclusive right-to-left transforamenal flow. We conclude that foramen
      ovale/atrial septum size ratio and Doppler interrogation of transatrial flow are
      helpful adjuncts in determining the presence of congenital heart disease in
      utero. In addition, early detection of abnormal foramen ovale/atrial septum size
      ratio may predict whether left or right ventricular development will be impaired
      throughout gestation, even before gross disparity of ventricular size is
      apparent.

PMID- 12797034
TI  - Is the ultrasound definition of fluid collections in non-immune hydrops fetalis
      helpful in defining the underlying cause or predicting outcome?
AB  - The ultrasound findings in 132 patients with non-immune hydrops referred for
      echocardiographic assessment were retrospectively reviewed. Structural assessment
      was combined with evaluation of pleural and pericardial effusions, ascites and
      skin edema. Patients were divided into groups based on the underlying etiology of
      hydrops. Seventy patients were found to have cardiac abnormalities, including 45
      with structural heart disease. Other causes included. chromosomal anomalies,
      infection, extra-cardiac anomalies, genetic syndromes and, in 40 patients,
      unknown cause. Analysis of patterns of fluid accumulation revealed a
      significantly decreased incidence of pleural effusions and ascites in fetuses
      with an underlying cardiac abnormality. Cardiomegaly based on the cardio-thoracic
      ratio was significantly more frequent in the cardiac group. When patients were
      grouped by outcome, no pattern of fluid distribution was found to be
      characteristic for survival or death. We conclude that ultrasound definition of
      fluid collections in non-immune hydrops may be helpful in predicting the
      underlying cause of the hydrops, although there are no specific patterns
      predictive of outcome.

PMID- 12797037
TI  - Ultrasound measurements of fetal limb bones.
AB  - In order to establish the growth patterns of fetal limbs, measurements of femur,
      humerus, tibia, fibula, radius and ulna were made by ultrasound and related to
      gestational age. To this end, 2317 normal singleton pregnant women were studied
      cross-sectionally at 13-40 weeks of gestation. Patients were selected on the
      basis of a certain last menstrual period, history of regular cycles and at least
      one ultrasound scan before 16 weeks confirming gestational age. Linear growth of
      all limb measurements was observed between 13 and 28 weeks of gestation. From
      this gestational age onwards, a flattening of the growth curve was seen. A second
      degree polynomial equation turned out to be the best model to describe this
      phenomenon. The measurements of all six fetal long bones showed a high
      correlation with menstrual age (r >or= 0.99). The femur displayed the largest
      mean weekly increments (2.8 mm per week from 13 to 28 weeks and 1.7 mm per week
      from 29 to 40 weeks of gestation) and the radius had the smallest (2.08 mm per
      week from 13 to 28 weeks and 1.25 mm per week from 29 to 40 weeks' gestation).
      Considering inter and intraoperator variations and the weekly increment of fetal
      long bone length, a correct evaluation of limb growth is possible for the femur
      every week before 28 weeks and every 2 weeks after 28 weeks. For the remaining
      limb bones, a correct evaluation is possible every 2 weeks at all gestational
      ages.

PMID- 12797038
TI  - Continuous maternal hyperoxygenation in the treatment of early fetal growth
      retardation.
AB  - Continuous maternal hyperoxygenation treatment (2.5 l/min by means of a
      nasopharyngeal cannula) was given in four patients presenting with intrauterine
      growth-retarded (IUGR) fetuses and decelerative fetal heart rate (FHR) patterns
      at 27-28 weeks of gestation. The effect of maternal hyperoxia was studied
      longitudinally. Neither the incidence of generalized fetal movements (FGM%) nor
      the pulsatility index of the internal carotid artery increased under hyperoxia.
      In fact, both variables decreased progressively. FHR variation was abnormal prior
      to the start of hyperoxygenation and showed a slight but transient increase. On
      average, maternal hyperoxygenation 'resulted' in a prolongation of the duration
      of pregnancy of 9 days. The neonatal mortality was similar in the study group as
      compared to a control group of IUGR infants. However, hypoglycemia,
      thrombocytopenia and disseminated intravascular coagulation at birth were found
      more frequently in the study group. Conversely, blood gas abnormalities were less
      frequent in the fetuses of mothers that were treated with oxygen. We conclude
      that positive effects of oxygen therapy in IUGR fetuses remain uncertain and that
      detrimental effects due to prolongation of intrauterine malnutrition have not as
      yet been sufficiently excluded.

PMID- 12797039
TI  - Transvaginal ultrasonic assessment of the early fetal brain.
AB  - The introduction of high resolution transvaginal transducers has expanded our
      knowledge of the first and early second-trimester fetus. This article describes
      transvaginal assessment of normal brain development. The feasibility of early
      detection of various fetal central nervous anomalies, such as anencephalus,
      exencephalus, hydrocephalus, Dandy Walker syndrome and myelomeningocele is
      described.

PMID- 12797040
TI  - Diagnosis of fetal lung maturity by ultrasound: a new method and first results.
AB  - The first results are presented of a method to determine the maturity of fetal
      lung by sonography. By comparing the frequency characteristics of lung echoes to
      those from the fetal liver as a reference organ, we avoid the known pitfalls
      which previously made it impossible to standardize fetal lung changes with
      gestation. We examined 222 patients between 27 and 39 completed weeks of
      gestation. In one ultrasound section we depicted fetal lung and liver
      simultaneously. Switching to A-mode we registered the frequencies contained in
      the video envelope in both organs. The registered frequencies were entered
      digitally in to a computer and checked for mean frequency, maximum frequency and
      minimum frequency. Afterwards, the ratio of the frequencies of the lung and liver
      were obtained. For all weeks of gestation, the mean value and standard deviation
      were calculated. We found the liver to be an adequate reference organ, since
      there is no change of the reflection pattern between the different weeks of
      gestation, while significant changes were registered in the fetal lungs. A
      quotient of Q(mean) lower than 1.1 suggests lung maturity, while values over 1.1
      point to immaturity. This appeared to be confirmed in 13 patients who had
      agreement between amniotic fluid lecithin values and Q(mean). Further comparisons
      with amniotic fluid results will have to validate these findings.

PMID- 12797041
TI  - Color Doppler studies in trophoblastic tumors: a preliminary report.
AB  - Ten women, referred because of a strong suspicion of gestational trophoblastic
      neoplasia, were examined by abdominal real-time ultrasound and color Doppler. The
      results were compared to those of pelvic angiography. In all but one case color
      Doppler examination revealed areas of increased vascularity. In all cases the
      findings of color Doppler and pelvic angiography agreed. Real-time ultrasound
      failed to detect abnormal uterine echoes in three of the patients where the other
      methods indicated tumor. The present study indicates that color Doppler could be
      of great value in a non-invasive assessment of trophoblastic tumors.

PMID- 12797042
TI  - The pathophysiology of acute syphilitic funisitis.
AB  - There is an increase in the number of cases of syphilis in pregnancy in the
      United States. Fetal death may occur in syphilis from acute or chronic
      infections. A case is presented in which an acute fetal infection occurred. The
      patient presented at 31 weeks' gestation, with a decrease in fetal movements and
      non-reactive cardiotocography. Ultrasound and Doppler analysis of the fetal
      heart, cerebral and umbilical arteries, aorta and umbilical vein led to the
      suspicion of acute cardiac failure. An amniocentesis yielded a white cell count
      of 1122 white blood cells, with 91% polymorphs, but the Gram stain was negative.
      The fetus developed a persistent bradycardia and was delivered. The diagnosis of
      acute severe syphilitic funisitis was suspected from histological sections of the
      cord. Diagnosis was established from maternal and fetal blood. Modern ultrasound
      techniques, including imaging, Doppler and cardiotocography, can lead to the
      analysis of the pathophysiology of disease states. An acute syphilitic infection
      should be suspected when this constellation of findings is found.

PMID- 12797043
TI  - Increased middle cerebral artery blood flow impedance in fetal subdural hematoma.
AB  - This case describes the prenatal diagnosis at 30 weeks' gestation of a posterior
      fossa subdural hematoma. Doppler velocimetry studies of the middle cerebral
      artery at that time showed an abnormally high resistance pattern with reverse end
      diastolic flow. Ultrasonic assessment of the fetus indicated that there was
      associated quadriplegia. No cause for the lesion was demonstrated. A fetal blood
      sample, obtained by cordocentesis, revealed a normal karyotype. Fetal blood gas
      analysis was also normal. The pregnancy was terminated at the parents' request.

PMID- 12797044
TI  - Transvaginal color Doppler in gynecology.

PMID- 12797045
TI  - Highest or lowest values of impedance flow in malignancy?

PMID- 12797047
TI  - Ultrasound and ovarian cancer.

PMID- 12797048
TI  - First-trimester fetal karyotyping: CVS or early amniocentesis?

PMID- 12797049
TI  - Toxoplasmosis and pregnancy.

PMID- 12797050
TI  - Randomized study of early amniocentesis versus chorionic villus sampling: a
      technical and cytogenetic comparison of 650 patients.
AB  - In a prospective randomized trial of 650 patients at 10-13 weeks' gestation,
      early amniocentesis was compared to chorionic villus sampling (CVS) for
      successful sampling and cytogenetic results and the speed with which results can
      he obtained. The indications for fetal karyotyping were advanced maternal age,
      parental anxiety or a family history of chromosomal abnormality in the absence of
      a balanced parental translocation. At early amniocentesis, 10 ml of amniotic
      fluid were successfully obtained in all 324 cases, in 320 (98.8%) at the first
      attempt and in four cases (1.2%) after two needle insertions. CVS provided
      sufficient material for cytogenetic analysis in 314 of 326 (96.3%) cases at the
      first attempt and in nine (2.8%) after two needle insertions; in three cases only
      maternal tissue was obtained and subsequently early amniocentesis was performed.
      Cell culture and chromosomal analysis were successful in 318 of 324 (98.1%) cases
      of early amniocentesis and in 321 of the 323 (99.4%) cases of CVS where villi
      were obtained. The median interval between sampling and successful result from
      cell culture was 12 days for early amniocentesis and 11 days for CVS. Mosaicism
      was detected in five cases of CVS but in none of the early amniocenteses; three
      of these cases were confirmed as true fetal mosaics. This study illustrates that
      early amniocentesis is a viable alternative to CVS for first-trimester fetal
      karyotyping. The results of the continuing prospective 1 trial will establish the
      safety and cytogenetic accuracy of the two techniques.

PMID- 12797051
TI  - Fetal toxoplasmosis: ultrasonographic signs.
AB  - Eighty-nine cases of proven Toxoplasma gondii fetal infection were studied in
      order to describe the morphological lesions which could be demonstrated on
      ultrasound examination; these were present in 32 of the infected cases. Cerebral
      ventricular dilatation was the most common sign and was generally bilateral and
      symmetrical. Its evolution was always very rapid over a period of a few days.
      Other signs observed included intracranial and intrahepatic densities, increased
      thickness and hyperdensity of the placenta, ascites and rarely pericardial and
      pleural effusions. Thirteen fetuses demonstrated two or more ultrasound features.
      Intrauterine growth retardation and microcephaly were not observed.
      Ultrasonographic assessment of the fetus injected with Toxoplasma gondii is
      important. It improves the reliability of prenatal diagnosis and is of important
      prognostic value in cases with severe brain lesions, but is of little value in
      detecting brain necrosis without ventricular dilatation.

PMID- 12797052
TI  - First- and early second-trimester oligohydramnios-a predictor of poor fetal
      outcome except in iatrogenic oligohydramnios post chorionic villus biopsy.
AB  - Whereas a well-known association exists between oligohydramnios and renal
      agenesis, renal dysplasia, urinary tract obstruction and intrauterine growth
      retardation in the second half of pregnancy, the causes and prognosis of early
      oligohydramnios are less known. Twelve cases of first- and early second-trimester
      oligohydramnios were detected out of 5000 fetal screenings for malformation
      detection. Two out of these 12 cases occurred in patients who had undergone
      chorionic villus sampling, two were associated with premature rupture of
      membranes, six were associated with fetal cardiac malformations and two cases
      were idiopathic. Whereas ten out of 12 cases ended in intrauterine fetal death,
      spontaneous or therapeutic abortions, in the two cases which developed after
      chorionic villus sampling the oligohydramnios was self-limiting and these two
      pregnancies ended in term deliveries of normal, healthy neonates. It may be
      concluded that oligohydramnios in the first half of gestation bears a poor fetal
      prognosis except in cases where it follows chorionic villus sampling.

PMID- 12797053
TI  - Doppler study of the fetal circulation during long-term maternal hyperoxygenation
      for severe early onset intrauterine growth retardation.
AB  - In 21 severely growth-retarded, hypoxemic fetuses at 22-30 weeks' gestation, the
      effect of long-term maternal hyperoxygenation on serial Doppler measurements of
      the fetal descending thoracic aorta mean velocity (Vm), common carotid artery
      pulsatility index (PI) and umbilical artery PI was investigated. The treatment
      was continued on average for 4 weeks and delivery, at 26-34 weeks, was decided
      for fetal or maternal indications. In the subgroup of 12 fetuses that survived,
      the mean aortic V(m) increased within 72 h of maternal hyperoxygenation. This
      increase continued for 1-8 weeks, after which there was a decrease to
      pretreatment values. In the subgroup of neonatal deaths (n = 5)) there was a non
      significant increase in mean aortic V(m). In the subgroup of intrauterine deaths
      (n = 4), there was a non-significant trend for continuing deterioration in mean
      aortic V(m) throughout the period of maternal hyperoxygenation. The mean carotid
      PI did not change significantly in any of the subgroups during maternal
      hyperoxygenation. However, in the subgroup that survived there was a tendency for
      improvement and in the subgroup of intrauterine deaths a tendency for
      deterioration. The mean umbilical artery PI did not change significantly in any
      of the groups or subgroups during maternal hyperoxygenation. Therefore,
      measurement of aortic V(m) is a useful indicator of fetal response to maternal
      hyperoxygenation and its increase constitutes a favorable prognostic factor.

PMID- 12797054
TI  - Doppler ultrasound examination of the renal artery in healthy women, normotensive
      pregnant women and in pre-eclampsia.
AB  - A combination of real-time linear array ultrasound scanning and pulsed Doppler
      ultrasonography was used to record blood flow signals from the right renal artery
      in 17 healthy women, in 15 normotensive pregnant women and in I7 women with pre
      eclampsia. The maximum blood velocity waveforms were analyzed for pulsatility
      index and systolic/diastolic ratio (S/D ratio). As compared with the two healthy
      groups, in pre-eclamptic women the pulsatility index was slightly lower (p <
      0.05), and the systolic/diastolic ratio non-significantly different. These
      variables were unrelated to mean arterial pressure or the degree of proteinuria.
      A theory of renal arteriovenous shunts in pre-eclampsia is proposed. Doppler
      ultrasound examination of the renal artery would seem to be of limited value-for
      the purpose of monitoring renal vascular pathology in pre-eclampsia.

PMID- 12797055
TI  - Fetal aortic diameter pulse wave response to changes in maternal position after
      membrane rupture.
AB  - An ultrasonic phase-locked echo-tracking system was used in order to study human
      fetal hemodynamics in relation to maternal postural changes after membrane
      rupture. Diameter pulse waves were recorded in the descending aorta of 17 fetuses
      presenting by the vertex in normal singleton pregnancies, with the mother in
      three different positions. The first measurements were made with the mother in
      the slightly left lateral recumbent (horizontal), then upon transition to the
      upright (70 degrees), and finally upon return to the horizontal. Change from the
      horizontal to the upright position produced a moderate but significant increase
      (p < 0.05) in maternal heart rate, while the systolic and diastolic blood
      pressures remained unchanged. No significant changes were seen in the fetal pulse
      wave variables (i.e. end-diastolic diameter, relative pulse amplitude, maximum
      incremental velocity, late decremental velocity, pulse duration, relative crest
      time and pulse wave velocity). The absence of fetal hemodynamic changes possibly
      reflects the presence of a protective effect against I gravitational stress to
      the fetal cardiovascular system provided by the remaining volume of amniotic
      fluid and the abundant fetal extracellular water.

PMID- 12797056
TI  - Myocardial contractility in the anemic human fetus.
AB  - Severely anemic fetuses in Rh-isoimmunized pregnancies are often found to have
      hydrops and the etiology is debated. Fifteen fetal blood samplings were performed
      in nine fetuses for determination of the degree of anemia and of the acid-base
      balance. Waveform analysis was performed on the maximum blood velocity curve in
      the umbilical arteries and the ascending fetal aorta, obtained by means of a
      pulsed Doppler technique. The blood acceleration in the ascending aorta increased
      down to a hematocrit of 0.18 and a hemoglobin concentration of 65 g/l, which
      might constitute a cardiac response to the anemia aimed at maintaining the
      peripheral blood circulation. Below these levels there was a decrease in blood
      acceleration, which could be caused by impaired cardiac oxygenation. This
      relationship could be described as a six-power function (r = 0.87; p = 0.032). A
      second-power relationship was found between the umbilical artery pulsatility
      index and the blood acceleration in the fetal ascending aorta (r = 0.64; p =
      0.0418), which suggests that the cardiac pump function can alter the blood
      velocity waveform in the umbilical arteries.

PMID- 12797057
TI  - Ultrasound findings in gestations destined for unanticipated fetal demise.
AB  - There are few reports of ultrasound findings in the second and third trimesters
      preceding intrauterine fetal demise. To describe these findings, the ultrasound
      assessments of 36 structurally normal singleton fetuses with subsequent
      intrauterine fetal demise were compared to gestational age-matched controls.
      Compared to controls, it was found that biparietal diameter, head circumference,
      femur length and estimated fetal weight were all decreased, abnormalities of
      amniotic fluid volume were more frequent, but the cephalic index was not
      different. Upon delivery, the group with subsequent intrauterine fetal demise was
      not found to have any major anomalies, but had a high incidence of abnormal
      umbilical cord position, abruptio placentae, chorioamnionitis and meconium
      aspiration.

PMID- 12797058
TI  - Prognostic appraisal of success and failure in an in vitro fertilization program
      by transvaginal Doppler ultrasound at the time of ovulation induction.
AB  - In 323 stimulated cycles of women participating in in vitro fertilization
      treatment, a transvaginal Doppler examination was performed on the day of
      ovulation induction to investigate the value of blood flow velocimetry of the
      uterine artery. The results showed a significantly lower pulsatility index in
      patients who conceived (n = 42) compared with those who did not become pregnant
      (n = 272). The differences were especially marked during the first cycles. These
      results suggest that studies of the uterine hemodynamic response are useful in
      appraising the likelihood of success of implantation after embryo transfer.

PMID- 12797059
TI  - Transvaginal color Doppler sonography of ovarian masses with pathological
      correlation.
AB  - This report describes the correlation of pathological findings with transvaginal
      color Doppler sonography performed preoperatively on 26 ovarian masses. The
      pulsatility indices of benign lesions (1.9 +/- 0.7) were higher than those of
      malignant ones (0.7 +/- 0.2) (p = 0.03). Low pulsatility indices (< 1.0) were
      found in three relatively vascular benign lesions (one immature teratoma, one
      cystadenoma containing a dermoid cyst, one endometrioma), causing an overlap
      between the pulsatility indices of some benign and malignant masses. There
      appears to be significant potential for discrimination between benign and
      malignant ovarian masses with transvaginal color Doppler sonography.

PMID- 12797060
TI  - Sonographic depiction of postmenopausal endometrium with transabdominal and
      transvaginal scanning.
AB  - The thickness of the endometrium was measured in postmenopausal women by both the
      transvaginal and transabdominal ultrasound approaches in two separate groups of
      patients. The first group consisted of 90 women who received a transabdominal
      scan of the endometrium before dilatation and curettage or hysterectomy for
      either postmenopausal bleeding or uterine prolapse. The second group consisted of
      111 women who underwent a transvaginal scan of the endometrium for similar
      postmenopausal conditions. Both methods suggested that an endometrial thickness
      of 5 mm may be used as a cut-off level in the conservative management of patients
      with postmenopausal bleeding or in a screening program for endometrial carcinoma.
      Patient acceptance and image quality were better in the group examined
      transvaginally. The proximity of the transvaginal probe to the endometrium, in
      the absence of a full bladder compressing the endometrium, revealed a unique
      group of patients with atrophic endometrium but thick endometrial cavity caused
      by intracavity fluid. In the presence of uterine fibroids distorting the uterine
      cavity, transvaginal scanning was better than transabdominal scanning for
      visualizing the endometrium. The transabdominal full-bladder technique can be of
      value in detecting asymptomatic bladder pathology.

PMID- 12797061
TI  - In utero appearance of idiopathic infantile arterial calcification: ultrasound
      study of a 28-week fetus.
AB  - An ultrasound study of a 28-week gestation demonstrated changes of poor cardiac
      function associated with calcifications of the wall of major arteries. Sudden in
      utero deterioration into hydrops prompted the delivery of a female infant who was
      diagnosed at autopsy of having a rare disease entity, idiopathic infantile
      arterial calcification. When a hydropic fetus is defined by ultrasound, this rare
      diagnosis should be included in the diagnostic considerations. Recent reports
      suggest successful therapy regimens for an otherwise fatal disease, making
      accurate diagnosis especially important.

PMID- 12797062
TI  - Electrophysiological principles and fetal antiarrhythmic therapy.

PMID- 12797063
TI  - ISUOG: a melting pot of practitioners.

PMID- 12797064
TI  - Direct fetal therapy for cardiac arrhythmias: who, what, when, where, why and
      how?

PMID- 12797065
TI  - Do velocity indices measure resistance?

PMID- 12797066
TI  - Fetal tachyarrhythmias: transplacental and direct treatment of the fetus-a report
      of 60 cases.
AB  - From 1981 to 1990, 60 fetuses with tachyarrhythmia (21-39 weeks of gestation)
      were treated in utero. Of these, 54 were cases of supraventricular tachycardia,
      and six of atrial flutter. Non-immune fetal hydrops was present in 21 cases with
      supraventricular tachycardia and in five cases with atrial flutter, a total of 26
      cases.Transplacental treatment by maternally administered antiarrhythmic drugs
      (digoxin only or in combination with verapamil) produced good results in non
      hydropic fetuses. In this group, all 34 fetuses survived. In fetuses with
      hydrops, 20 out of 26 survived. In 13 fetuses of the 26 with hydrops, direct
      fetal therapy was performed in addition to the transplacental therapy when the
      tachyarrhythmia was refractory to transplacental treatment. During the 9 years of
      this study, a variety of direct treatment regimes have been used consisting of
      intraperitoneal and/or umbilical intravenous administrations of different drugs.
      Since 1988, umbilical vein punctures have shown that the transplacental passage
      of digoxin (and amiodarone) is hampered in the presence of hydrops, and direct
      treatment may he necessary in these cases. Amiodarone seems to he the drug of
      choice for direct therapy. It is highly effective in supraventricular tachycardia
      and atrial flutter. The long elimination half-time of amiodarone reduces the
      number of umbilical cord punctures needed to maintain the therapeutic drug level
      in the fetus.

PMID- 12797067
TI  - The influence of angiotensin II-induced vasoconstriction on common carotid artery
      blood flow and velocity-time profiles in normal women.
AB  - Non-invasive methods of measuring blood velocity, especially Doppler velocimetry,
      are being increasingly used in obstetrics to provide observational information.
      We report a preliminary study of their usefulness in experimental studies.
      Doppler velocimetry was used to assess blood flow and velocity-time profiles in
      the common carotid artery of seven women of reproductive age before and during
      the incremental administration of angiotensin II. Angiotensin II infusion evoked
      the expected increments in systolic and diastolic arterial pressure and fall in
      heart rate. Angiotensin II was associated with a dose-dependent fall in maximum
      blood velocity, which, at an average rise in systolic blood pressure of 23 mmHg,
      had fallen from 91 +/- 16 to 52 +/- 4 (mean +/- SD, p < 0.01). Absolute maximum
      blood velocity was strongly correlated with systolic and diastolic blood
      pressures (p < 0.001 for both). The minimum velocity was unaltered throughout,
      and the calculated flow did not change significantly (490 +/- 100 cf. 380 +/- 50
      ml/min). Overall, these findings are in agreement with those previously reported
      using invasive methods of monitoring flow during angiotensin II infusion, and
      further support the usefulness of Doppler velocimetry as an investigative tool in
      human physiology and pharmacology.However, the pulsatility index, resistance
      index and systolic/diastolic velocity ratio all fell significantly during
      angiotensin II infusion (p < 0.01 for all). The conventional interpretation of a
      fall in these indices, i.e. reduced downstream resistance, is clearly erroneous
      under these circumstances, since angiotensin II induces arteriolar
      vasoconstriction. This illustrates the importance of interpretation of Doppler
      velocity envelopes in the light of pharmacological mechanisms likely to be evoked
      by the experimental procedure.

PMID- 12797068
TI  - Interpretation of pulsatility index in feeder arteries to low-impedance vascular
      beds.
AB  - A simple electrical circuit is proposed as a model for peripheral vascular beds
      of low impedance. The model consists of a flow and pressure source, i.e. the
      'feeder' artery, with the vascular bed represented by a Zener diode Z giving rise
      to a 'back pressure' P(z) and a pure resistance R. By applying Ohm's law to the
      definition of pulsatility index PI(flow) of flow in the feeder artery, it is
      shown that PI(flow) is dependent only on the mean blood pressure (input), the
      pulse pressure and P(z), and is independent of R. For those vascular beds where
      the impedance is largely resistive, e.g. the brain, the kidney and the uterine
      placental complex, it is suggested that P(z) may be a more useful characterizing
      parameter than the value of PI(flow) as at present used by some workers.

PMID- 12797069
TI  - Doppler ultrasonography in early pregnancy does not predict adverse pregnancy
      outcome.
AB  - A transvaginal color and pulsed Doppler study was performed on 330 pregnancies at
      7-16 weeks of gestation. Blood flow velocity waveforms were recorded from the
      main uterine arteries and their branches (arcuate and trophoblastic vessels) and
      from the umbilical arteries. The systolic/diastolic velocity ratio and the
      pulsatility index were calculated as indices of vascular resistance,
      respectively, at uterine and umbilical levels. A total of 282 patients had an
      uneventful pregnancy outcome, 19 developed an early pregnancy failure (missed
      abortion, n = 8; anembryonic pregnancy, n = 11) and 29 developed later
      complications such us hypertension (n = 10), fetal growth retardation (n = 13) or
      both n = 6). In normal pregnancies, Doppler-measured vascular resistances
      significantly decreased with advancing gestation at the level of both uterine and
      umbilical circulations. When the Doppler indices of the patients with early
      pregnancy failure or with later complications were compared to those of normal
      pregnancies, no evident differences were found in either of the vascular
      districts considered. However, in the patients who developed hypertension and/or
      fetal growth retardation, abnormal velocity waveforms were frequently present in
      uterine and umbilical arteries during second- or third-trimester examinations.
      Our results suggest a limited clinical value of Doppler velocimetry in early
      pregnancy.

PMID- 12797070
TI  - Screening for fetal anomalies during the first trimester of pregnancy:
      transvaginal versus transabdominal sonography.
AB  - Ultrasound is a sensitive tool for the diagnosis of fetal anomalies during the
      prenatal period. Most knowledge about the ultrasound images of such anomalies is
      based on abdominal scanning during the second trimester of pregnancy. The value
      of transvaginal sonography for evaluating fetal anomalies and a comparison with
      transabdominal sonography in the first trimester has, to our knowledge, so far
      not been studied. During a 12-month period, 800 pregnant women between 9 and 13
      weeks of gestation, underwent first a transabdominal scan followed by a
      transvaginal examination, in order to compare the value of the two techniques.
      Eight cases of fetal abnormality, including anencephaly, exencephaly, cervical
      myelomeningocele, cystic hygroma, omphalocele, posterior fossa cyst and
      syndactyly, were diagnosed by using the transvaginal sonographic approach. The
      standard abdominal technique failed to detect four of these anomalies, while in
      the other four only vague and non-specific fetal abnormalities could be
      demonstrated. All women with normal abdominal and vaginal sonograms in the first
      trimester were rescreened transabdominally at mid-gestation. Five patients with a
      variety of fetal anomalies, including hydrocephalus, agenesis of corpus callosum,
      bilateral ureteropelvic junction obstruction, right heart hypoplasia and
      tetralogy of Fallot, were identified in the rescreening procedure. One case of
      ventricular septal defect and coarctation of the aorta was not detected at either
      of the first or second screening procedures. Our findings show that transvaginal
      sonography is more sensitive than transabdominal sonography in the detection of
      first-trimester anomalies. However, since not all fetal anomalies are manifest so
      early in pregnancy, standard abdominal sonography in the second trimester is
      still recommended.

PMID- 12797071
TI  - The clinical significance of absent or reverse end-diastolic flow in the fetal
      aorta and umbilical artery.
AB  - The clinical utility of Doppler blood flow investigations of the fetal and
      fetoplacental vessels is still under debate as far as timing of the delivery is
      concerned. However, in cases of absent or reverse end-diastolic flow, fetal
      compromise is usually very severe. As a consequence, we have investigated the
      possibility of using this information as a guide to obstetrical management.
      Altogether, 32 fetuses with absent or reverse end-diastolic flow in the fetal
      descending aorta and/or umbilical artery were studied. Reverse flow was observed
      in 11 cases and absence of end-diastolic flow in 21 cases. The two groups are
      considered separately. No significant difference was found in the mean
      gestational age at delivery. However, a highly significant difference was found
      in the mean birth weight and perinatal mortality rate. All the cases of perinatal
      mortality were encountered in the group presenting with reverse flow (mortality
      rate, 63.6%). All the live fetuses were delivered by Cesarean section and no
      neonatal mortality was observed in this group. Two cases of handicap were
      observed, one in each group. In our experience, reverse flow indicates the
      necessity for immediate delivery if no other clinical contraindications are
      present. Absence of end-diastolic flow can be observed for longer periods without
      adverse outcome. Absence of end-diastolic flow always precedes the appearance of
      fetal distress. Therefore, we believe that, after exclusion of conditions such as
      fetal abnormalities or extreme prematurity, a planned delivery should be
      considered.

PMID- 12797072
TI  - Classification of tubal gestations by transvaginal sonography.
AB  - Transvaginal sonographic images of tubal pregnancies were correlated with the
      surgical findings in 191 patients having this condition. The sonographic
      appearance of the ectopic gestations was classified by the absence or presence of
      structures such as a 'tubal ring' containing the yolk sac, embryonic structures,
      heart activity, a sonolucent or irregularly echogenic gestational sac, dilated
      Fallopian tube with amorphous content, fluid in the pelvis and an empty uterus.
      The following classifications were made: Type Ia (n = 43) A well-defined 'tubal
      ring' and a beating heart with or without discrete embryonic or extra-embryonic
      structures. Type Ib (n = 48) A 'tubal ring' containing embryonic and/or extra
      embryonic structures without heart beats. Type II (n = 64) An ill-defined or thin
      tubal wall containing sonolucent or an irregularly echogenic core but not
      embryonic or extra-embryonic structures. Type III (n = 28) Free pelvic fluid and
      an empty uterus in patients with positive serum beta-hCG levels. The outline of
      the tube cannot be visualized. Surgery revealed unruptured tubal pregnancies in
      90 patients of the combined groups of Types Ia and Ib. In one additional patient,
      a tubal rupture was found. In the Type II patients, 26 tubal pregnancies with
      blood clots in the tube but no evidence of bleeding into the pelvis, and 38 tubal
      ruptures or abortions were diagnosed. All Type III patients had ruptured tubal
      pregnancies or bleeding tubal abortions. In eight patients (4.2%), the only
      sonographic finding was an empty uterus, and these cases were erroneously
      diagnosed as not having an ectopic pregnancy (false negatives). There were two
      false-positive cases in which a tubal ring was detected, and this was related to
      an hemorrhagic corpus luteum. When used for diagnosing tubal pregnancy, the
      transvaginal scanning technique (together with beta-hCG in Type III cases)
      carries a sensitivity of 95.8% and specificity of 99.9%. It is an invaluable tool
      in the diagnostic work-up and management of patients with suspected ectopic
      gestation.

PMID- 12797073
TI  - Tracking of fetal breathing movements by pulsed Doppler ultrasound.
AB  - Fetal breathing movements form a useful means of monitoring fetal conditions and
      functional development. Precise quantitative evaluation of fetal breathing
      movements requires the development of a continuous automated technique. A
      preliminary study of Doppler signals due to fetal breathing movements was carried
      out using a cardiotocograph in which the normal high-pass 'thump' filter had been
      removed. A pulsed Doppler system was then modified to produce five simultaneous
      outputs representing movement at depths separated by 1.5-cm intervals. These
      outputs represent the displacement inside tissue at the various depths. Signal
      processing was executed on a 32-bit computer with an analog-to-digital converter.
      On-line processing using a zero-crossing method and an off-line high-accuracy
      displacement estimation technique using an arc-tangent method were applied. Using
      computerized signal processing, it was possible to detect movements of a few
      hundred microns representing fetal breathing movements while rejecting gross
      movements due to maternal breathing, etc. Although further studies are required
      before clinical application, it appears that quantitative assessments of fetal
      breathing movements should be possible with this technique.

PMID- 12797074
TI  - Ultrasound measurement of the fetal head: computer versus operator.
AB  - In obstetrical ultrasound practice, biparietal diameter, occipito-frontal
      diameter and head circumference are among the most commonly used fetal
      measurements. To minimize the limitations associated with manual measurement, we
      have undertaken an investigation with a focus on (1) the design of a personal
      computer-based system for automated measurements of biparietal diameter, occipito
      frontal diameter and head circumference, and (2) integration of such a system
      (including measurements of abdomen and femur) into the routine obstetrical
      ultrasound examination. This report presents preliminary results of a comparison
      of computer-determined fetal head measurements with those obtained by an
      operator. Data were obtained from 75 consecutive singleton fetal ultrasound
      examinations free of any obvious structural anomalies. The computer obtained
      acceptable measurements of biparietal diameter, occipito-frontal diameter and
      head circumference from 74 images and failed on one image. There was a highly
      significant correlation between computer-determined measurements of biparietal
      diameter (r = 0.986), occipito-frontal diameter (r = 0.958) and head
      circumference (r = 0.972) and those obtained by the operators. The mean
      measurement difference (computer minus operator) was 1.87 +/- 1.94 mm for
      biparietal diameter, 2.82 +/- 4.13 mm for occipito-frontal diameter and -0.36 +/-
      9.87 mm for head circumference. These differences were independent of the
      operator's identity, the instrument used and gestational age. The key finding of
      this study is that, with the use of inexpensive personal computer technology, it
      is possible to design and implement a system that can give fetal head
      measurements which correlate highly with manual determination by a skilled
      operator and which take a fraction of the time.

PMID- 12797075
TI  - Ultrasound instead of last menstrual period as the basis of gestational age
      assignment.

PMID- 12797076
TI  - Intrafollicular blood flow during human ovulation.

PMID- 12797077
TI  - Leveling out.

PMID- 12797079
TI  - Fetal karyotyping: which technique at what gestation?

PMID- 12797078
TI  - Ectopic pregnancy: the role of ultrasound-directed injection.

PMID- 12797080
TI  - Sampling success and risk by transabdominal chorionic villus sampling,
      transcervical chorionic villus sampling and amniocentesis: a randomized study.
AB  - A total of 3347 women were randomized to either transabdominal chorionic villus
      sampling, transcervical chorionic villus sampling or amniocentesis. Unless
      induced or spontaneous abortion had occurred, they had all completed up to 28
      weeks of pregnancy at the time of analysis. No significant difference was seen
      between total fetal loss in the transabdominal chorionic villus sampling group
      and the amniocentesis group (6.2% and 6.6%, respectively, SE difference 0.92%, p
      = 0.01). The total fetal loss in the transcervical group was 10.1%. When the
      number of failed procedures and those cases which were evaluated as infeasible
      for the assigned method, are compared, the overall sampling efficacy is less good
      transcervically than transabdominally. After pooling our data with data from the
      Canadian randomized study and the American non-randomized study, the difference
      in risk between transcervical chorionic villus sampling and amniocentesis was
      2.1%, SE difference = 0.64%, p = 0.8.

PMID- 12797081
TI  - Amniocentesis with increased cell yield, obtained by filtration and reinjection
      of the amniotic fluid.
AB  - In order to increase the cell numbers obtained by amniocentesis, a new
      amniocentesis technique has been developed and we report preliminary results. The
      amniotic fluid is aspirated in the usual manner and reinjected immediately into
      the amniotic cavity after passage through a filter which retains the cells from
      the fluid. By this procedure, the cells from a relatively large volume of
      amniotic fluid are concentrated on the filter while only a small volume of
      amniotic fluid is finally removed. The method has been tested on 30 pregnant
      women referred for prenatal diagnosis. The mean culture time was 8.3 days and no
      immediate side-effects were observed.

PMID- 12797082
TI  - Umbilical artery velocimetry and non-stress test in monitoring high-risk
      pregnancies. A comparative longitudinal study.
AB  - In a longitudinal comparative study, umbilical artery velocimetry and the non
      stress test were used in parallel for surveillance of 153 hospitalized high-risk
      pregnancies. The occurrence of abnormal flow velocity waveforms of the umbilical
      artery, with increased pulsatility index but maintained diastolic flow velocity,
      was an inconsistent finding and often related to pregnancy complications other
      than intrauterine growth retardation. Among patients with small-for-gestational
      age fetuses or pre-eclampsia with a small-for-gestational age fetus, there was a
      significantly higher frequency of abnormal umbilical flow velocity waveforms.
      This was a consistent finding and was often associated with an absence of
      diastolic flow velocity and operative delivery for fetal distress. An abnormal
      non-stress test had a significant relationship with intrauterine growth
      retardation, but a lower predictive capacity for this condition than the abnormal
      umbilical artery flow velocity waveform. In patients with small-for-gestational
      age fetuses and no other complication of pregnancy, umbilical artery velocimetry
      can be used as a reliable tool for identifying those fetuses that need
      intensified surveillance. In cases with additional complications, a combined use
      of blood velocimetry and the non-stress test is advocated.

PMID- 12797083
TI  - Sensitivity and specificity of routine antenatal screening for congenital
      anomalies by ultrasound: the Belgian Multicentric Study.
AB  - United States and European consensus views differ on the place of routine
      ultrasound scans during pregnancy and the validity of such scans as screening
      tests for fetal malformations in the general population is still under debate.
      Four ultrasound laboratories from Obstetric and Gynecology departments of Belgian
      University hospitals and affiliated hospitals have conducted a prospective study
      from 1984 to 1989 to compare the anomalies discovered in ultrasonic screening of
      the fetus with the anomalies of the neonates. Of 16,370 pregnant women at normal
      risk for congenital anomalies attending the antenatal clinics of these hospitals,
      16,072 have had at least one ultrasound screening for congenital anomalies
      (98.5%). Congenital anomalies, single or multiple and 'minor' or 'major', were
      clearly defined in order to allow comparisons. The excluded congenital anomalies
      were listed as defined in the Eurocat Register. A total of 381 fetuses (2.3%)
      were structurally abnormal. Of the 381, 154 were correctly detected by ultrasound
      (sensitivity 40.4%). Altogether 15,972 fetuses were true negatives (specificity
      99.9%). Eight (0.05%) were false positive for congenital anomalies. The positive
      predictive value was 95.1% and the negative predictive value was 98.6%.
      Ultrasound diagnoses were correctly achieved before 23 weeks of gestation for 21%
      of the anomalies. The gestational age, operator and technical dependence of
      ultrasound screening for congenital anomalies is discussed.

PMID- 12797084
TI  - Fetal echocardiography in multiple gestations.
AB  - We reviewed fetal echocardiograms from 36 multiple gestations from 20 weeks
      gestation to term. Seven sets of twins plus one set of triplets were referred
      because of a suspect cardiac anomaly in one fetus; heart disease was confirmed in
      one fetus of six sets of twins and in one triplet. Six sets were referred because
      of extracardiac malformations and heart disease was confirmed in two sets
      (including both twins in one set). The remaining case was detected in a patient
      sent for evaluation of karyotypic abnormality. Thus 11 fetal cardiac defects were
      detected in ten pregnancies. Chromosomes were abnormal in three of the anomalous
      fetuses. Two sets discordant for heart disease were monochorionic. Intervention,
      including a change in the planned location of delivery, or maternal
      digitalization for fetal congestive failure, occurred in six. We conclude that
      fetal echocardiography is feasible and useful in appropriate multiple gestations.
      Although often ethically complex, the information gained can be applied to
      patient management.

PMID- 12797085
TI  - The differential diagnosis of enlarged hyperechogenic kidneys with normal or
      increased liquor volume: report of five cases and review of the literature.
AB  - We report five cases of enlarged, hyperechogenic kidneys detected prenatally
      where the liquor volume was normal or increased. The etiology was different in
      all cases and included infantile and adult polycystic kidney disease, Perlman
      syndrome, trisomy 13 and cystic dysplasia. The differential diagnosis of such
      findings is discussed and other cases reported in the literature are reviewed.

PMID- 12797086
TI  - The impact of sonographic assessment of the endometrium and meticulous hormonal
      monitoring during natural cycles in patients with failed donor artificial
      insemination.
AB  - The present study was undertaken to determine whether the sonographic
      characteristics of the endometrium in the proliferative phase of the natural
      cycle combined with meticulous hormonal monitoring would have an impact on the
      prediction of conception. Fourteen women with regular ovulatory cycles were
      examined daily, from day 8 of the cycle, by transvaginal ultrasound through 16
      unstimulated cycles. All patients had had at least four previous unsuccessful
      donor artificial insemination cycles scheduled by basal body temperature records.
      During the study, donor artificial insemination was meticulously timed by
      hormonal and sonographic monitoring. Four clinical pregnancies occurred with a
      success rate of 29% per patient, or 25% per cycle. The endometrial thickness at
      the mid-proliferative phase (day 8) was significantly smaller in patients who
      conceived in comparison with patients who failed to conceive (0.33 +/- 0.07 cm
      vs. 0.59 +/- 0.03 cm; p < 0.01). The endometrial thickness on the day of the
      luteinizing hormone (LH) peak was not significantly different between the two
      groups. However, the amount of endometrial growth between day 8 of the cycle and
      the day of the LH peak was significantly greater in conception than non
      conception cycles (0.55 +/- 0.05 cm and 0.24 +/- 0.06 cm; p < 0.01). No
      difference in hormonal parameters was observed either on day 8 of the cycle or on
      the day of the LH peak between conception and non-conception cycles. On the day
      of the LH peak, an endometrium with typical triple line appearance and thickness
      of 0.6 cm or more was seen significantly more often in conception than non
      conception cycles (p < 0.05). No pregnancy occurred with an endometrium < 0.6 cm
      at the time of ovulation. The presence of the favorable endometrial pattern in
      the periovulatory phase was associated with a positive predictive value for
      pregnancy of 50% (sensitivity of 100% and specificity of 67%), whereas the
      negative predictive value of the hyperechoic pattern at the time of ovulation was
      100%. Our data show negative correlation between early growth of the endometrium
      and pregnancy in unstimulated cycles, suggesting that the amount of endometrial
      growth during the cycle up to ovulation may have an important role in
      implantation. The sonographic image of the endometrium in natural cycles provides
      useful information about the possible outcome of the treated cycle.

PMID- 12797087
TI  - Ectopic pregnancy: sonographically-guided transvaginal reduction.
AB  - The advanced modalities of vaginal ultrasonography and sensitive human chorionic
      gonadotropin assays have greatly facilitated the diagnosis of early ectopic
      pregnancy. The treatment spectrum for ectopic pregnancy ranges from a variety of
      conservative operative measures, including salpingectomy and operative
      laparoscopy, to various medical regimens or simply watchful observation alone. We
      report 12 cases in which the ectopic gestation was treated by transvaginal
      instillation of potassium chloride or methotrexate under sonographic guidance.
      Three of these, one of two patients receiving potassium chloride and two of six
      patients receiving methotrexate, later required a laparotomy. The level of beta
      subunit of human chorionic gonadotropin was found to be unreliable in predicting
      the outcome in these patients. Ultrasound follow-up is mandatory. A protocol for
      treatment is presented.

PMID- 12797088
TI  - Conservative treatment of ectopic pregnancies using a single echo-guided
      injection of methotrexate into the gestational sac.
AB  - The authors describe the possibility of the conservative treatment of five early
      ectopic pregnancies. A single injection of methotrexate into the tubal
      gestational sac was performed under vaginal ultrasound guidance. In all five
      cases, a clear ectopic gestational sac could be visualized. The pregnancies dated
      from the 5th to the 7th week of amenorrhea. Strict ultrasound follow-up following
      injection showed a gradual reduction in the size of the tubal gestational sac. At
      the same time, plasma beta-hCG gradually decreased to zero after a maximum time
      period of 25 days. Subsequent hysterosalpingography performed on all of the women
      demonstrated bilateral normal patent tubes. It is concluded that, in selected
      patients, transvaginal injection provides an alternative relatively non-invasive
      approach to the management of ectopic pregnancy. It is proposed that the adoption
      of a policy of earlier diagnosis and treatment may lead to a reduction in the
      incidence of some tubal causes of infertility.

PMID- 12797089
TI  - Ectopic pregnancy treatment using pelviscopic or vaginosonographically-guided
      intrachorionic injection of methotrexate and POR 8.
AB  - It is believed by some that the basis of modern first-trimester pregnancy care
      should involve screening for ectopic pregnancy using vaginal ultrasonography.
      This has led to this condition being diagnosed in most cases at an earlier stage
      than has previously been possible. This advance in diagnostic ability has
      introduced the concept of conservative management for this condition. The authors
      describe the conservative management of nine cases of ectopic pregnancy using
      intrachorionic injection of either methotrexate alone or in combination with POR
      8. In all cases less than 9 weeks had passed since the last menstrual period, and
      the ectopic pregnancies treated under ultrasound control were all thought to be
      viable. Five cases were treated using pelviscopy, whilst in another four the
      needle was guided using vaginal ultrasonography. There were no procedure-related
      complications. Following therapy, the women were followed up using serial levels
      of serum beta-hCG. In seven cases there was a gradual reduction to normal levels.
      There were two treatment 'failures'. In both these cases methotrexate alone,
      rather than in combination with POR 8, was used for injection. Although formal
      tests of tubal patency have not been performed in all cases, one woman in the
      series has since conceived and has a normal intrauterine pregnancy. It is
      concluded that vaginal instillation of methotrexate is an alternative treatment
      for early ectopic pregnancy. It should be limited to viable ectopic pregnancies
      whose chorionic cavities are less than 2.0 cm in diameter. A plan for the
      management of ectopic pregnancy is presented, involving selection for both
      ultrasound-guided injection and pelviscopic surgery. Laparotomy is not considered
      to be a treatment option in the majority of cases.

PMID- 12797091
TI  - First World Congress of ISUOG: a personal view.

PMID- 12797090
TI  - Puncture procedures utilizing transvaginal ultrasonic guidance.
AB  - The introduction of transvaginal sonography has enabled the use of this scanning
      method for guided puncture procedures. A total of 102 puncture procedures are
      described: 63 fetal reductions, eight punctures of ectopic pregnancies, 19
      drainages of pelvic contents, seven punctures of ovarian cysts, four diagnostic
      culdocenteses and one injection of a cervical pregnancy. Every procedure is
      discussed in detail. There was only one procedure-related complication. The
      advantages of the ultrasound-guided vaginal puncture procedure are its
      performance under real-time imaging, a low complication rate, a better pregnancy
      outcome when considering the reduction of multifetal gestations, and, most
      importantly, the fact that abdominal surgery can be avoided in several cases.

PMID- 12797092
TI  - Presentation of the 1991 Ian Donald Gold Medal to Alfred Kratochwil.

PMID- 12797093
TI  - Ian Donald's child comes of age.

PMID- 12797094
TI  - Human fetal foramen ovale flow velocity waveforms relative to fetal breathing
      movements in normal term pregnancies.
AB  - The relationship between foramen ovale flow velocity waveforms and high-amplitude
      fetal breathing movements was studied in ten normal term pregnancies using
      Doppler ultrasonography. Peak systolic and averaged flow velocities demonstrated
      a statistically significant increase during fetal breathing activity, suggesting
      a raised pressure gradient between the right and left atria. This could be
      explained by a temporal reduction in pulmonary venous return to the left atrium
      during the inspiratory phase of the fetal breathing cycle. The breathing-related
      increase in foramen ovale flow velocity suggests that fetal breathing activity
      facilitates the distribution of well-oxygenated blood to the aorta and cerebral
      circulation.

PMID- 12797095
TI  - Chromosomal anomalies in fetal congenital heart disease.
AB  - A series of 467 cases of congenital heart disease detected in prenatal life were
      analyzed to identify the forms of cardiac malformation associated with karyotypic
      defects and to calculate the incidence of chromosomal abnormalities associated
      with such malformations. Of these, 77 were proved to have chromosomal anomalies
      although not all were karyotyped. The results were analyzed in two ways. First,
      the whole series of 77 cases was examined in order to describe the form of
      congenital heart disease found in association as, although many cases were forms
      of heart disease known to be associated with chromosomal defects, several were
      unexpected. In many cases which proved positive, there were other abnormal
      findings on ultrasound, further suggesting a high likelihood of a chromosomal
      defect. Some cardiac defects, however, such as atrial isomerism or transposition
      of the great arteries, were not associated with trisomies. The second part of the
      study examined in detail the records of 124 cases of congenital heart disease
      seen in 1989, as these were more completely documented than the previous cases.
      No chromosomal anomaly was therefore thought to be missed. Of this group, 20
      (16%) proved positive. This is a higher rate than would be expected in an
      unselected population of live births. The difference between prenatal and
      postnatal life can be accounted for by the increased rate of spontaneous fetal
      loss in those with chromosomal defects. We conclude that, because of the high
      rate of chromosomal anomaly, all continuing pregnancies where congenital heart
      disease has been found in the fetus should be karyotyped unless specific types of
      heart defect which are rarely associated are confidently defined.

PMID- 12797096
TI  - The fetal mandible measurement: an objective determination of fetal jaw size.
AB  - The sonographic diagnosis of micrognathia has been limited by the lack of an
      objective measurement of the fetal mandible. A cross-sectional study of 134
      normal patients of known gestational age between 14 and 39 weeks' gestation was
      performed. Models to predict mandible length based on gestational age, biparietal
      diameter, head circumference or femur length were derived by least squares
      regression analysis. The 95% prediction limits were also derived. Utilization of
      these curves generated from a normal population should allow for a more sensitive
      and reproducible method to diagnose micrognathia in the fetus.

PMID- 12797097
TI  - Ethics, an emerging subdiscipline of obstetric ultrasound, and its relevance to
      the routine obstetric scan.
AB  - Ethics is an emerging subdiscipline of obstetric ultrasound because there are
      clinical dimensions of obstetric ultrasound that only ethics can identify and
      address. These dimensions concern the ethical obligations of physicians to their
      patients. Ethics is defined as the disciplined study of morality. Two fundamental
      principles of ethics are described, beneficence and respect for autonomy. How
      ethics can bring to light clinical dimensions of obstetric ultrasound that are
      insufficiently appreciated is illustrated with the example of the routine use of
      obstetric ultrasound in the second trimester. The authors conclude that prenatal
      informed consent for sonogram should be an integral part of obstetric care in
      countries, such as the United States, in which routine ultrasound is not
      endorsed.

PMID- 12797098
TI  - The physical and psychomotor development of children conceived by IVF and exposed
      to high-frequency vaginal ultrasonography (6.5 MHz) in the first trimester of
      pregnancy.
AB  - We examined the physical and psychomotor development of 33 infants conceived by
      in vitro fertilization (IVF) who were exposed to high-frequency transvaginal
      ultrasonography (HFTVS) (6.5 MHz) in the first trimester of pregnancy. The study
      group was composed of 21 singletons and six sets of twins. Thirty-three non-IVF
      controls were matched for birth weight, gestational age, sex, birth order, order
      in multiple delivery, mode of delivery, age at examination and parental age and
      education. Forty-five IVF infants who were not exposed to HFTVS and their matched
      controls also served as comparison groups. The Bayley scales were used to assess
      the psychosocial development of the infants studied. Increases in preterm
      delivery, low birth weight and Cesarean section rates were within the acceptable
      range for IVF babies. Mean birth weight, gestational age and birth weight
      percentiles of exposed IVF infants were lower than the expected mean for a normal
      population, but did not differ from that of non-exposed IVF infants. Mean
      percentiles of weight and length at examination were also low but not different
      from those of non-exposed IVF and matched control groups. However, percentiles of
      head circumference were normal at birth and at examination both in study and
      control groups. Overall, Bayley scores of exposed IVF infants were within the
      normal range and did not differ significantly from those of their matched
      controls and non-exposed peers. These scores were significantly correlated to
      birth weight, percentiles of birth weight and head circumference at birth and at
      examination, and to the mother's education. Twins had lower physical and mental
      indices than singletons, but did not differ from their controls.

PMID- 12797099
TI  - Is the quality of transvaginal images superior to transabdominal ones under
      matched conditions?
AB  - Transvaginal images, under matched conditions, are in general superior in quality
      to transabdominal sonograms. The difference is, however, not dramatic and
      instances frequently occur when the same quality and even inferior images are
      obtained on transvaginal examinations. The dominant factor is the amount of
      overlying tissues. For the same thickness, subcutaneous tissues have greater
      degrading characteristics. Subcutaneous tissues also mar the quality of images by
      giving rise to strong multiple reflection artifacts. The major factors for image
      degradation are associated with a moderate increase in the width of the
      ultrasonic beam and a large increase in the side lobes. The dramatic superiority
      of transvaginal imaging described in previous comparison studies is due
      principally to the use of higher frequencies, more strongly focused beams and
      closer positioning of tissues to the transducer.

PMID- 12797100
TI  - Comparison of total fetal activity measurement with the biophysical profile in
      predicting intra-amniotic infection in preterm premature rupture of membranes.
AB  - A comparison was made between measurement of total fetal activity and biophysical
      profile as predictors of infection in preterm premature rupture of membranes.
      Sixty-four patients with premature rupture of membranes, not in labor, between 24
      and 34 weeks' gestation were studied. All patients had an amniocentesis and 25
      patients were diagnosed as having intra-amniotic infection. The sensitivities of
      the tests were 96% and 92%, respectively, with specificities of 82% and 59%.
      Measurement of the total fetal activity had significantly better specificity.

PMID- 12797101
TI  - Fetal and uteroplacental blood flow in prolonged pregnancies. A clinical study.
AB  - In a prospective study during 1 year, 102 women with prolonged pregnancies (more
      than 294 completed gestational days) were followed with serial pulsed Doppler
      blood flow examinations every 2nd day, either to spontaneous onset of labor (n =
      82) or to induction of labor due to subsequently occurring complications (n =
      20). Mean aortic blood velocity did not change significantly with gestational age
      beyond 294 days either in fetuses with normal outcome or in fetuses that
      developed asphyxia at birth. The flow velocity waveforms in the descending aorta,
      the umbilical artery, the common carotid artery and the uterine artery did not
      change significantly compared to the values at term. Abnormal flow velocity
      waveforms in the fetal descending aorta, umbilical artery or uterine artery had
      no significant relationship to fetal asphyxia. Absence of diastolic flow
      velocities was not found in any of the vessels examined, indicating that the
      fetuses did not suffer from chronic hypoxia in utero and that aging of the
      placenta did not alter fetal and uteroplacental blood flow. Notching of the
      aortic flow velocity waveform was a common finding among prolonged pregnancies.
      The hemodynamic implications and consequences of this phenomenon are discussed.

PMID- 12797102
TI  - Braxton-Hicks contractions can alter uteroplacental perfusion.
AB  - Color flow imaging was used to study the effect of spontaneous low-amplitude
      uterine contractions (Braxton-Hicks) on flow velocity waveforms obtained from the
      main uterine artery in 13 women between 26 and 34 weeks' gestation. Eight women
      had abnormal waveforms, as defined by the presence of an early diastolic notch,
      and five women had normal waveforms. In the former group, three women with
      chronic hypertension were started on the calcium antagonist nifedipine during
      this study. Contractions, which were monitored by external tocography, occurred
      more frequently in the group with abnormal waveforms and were temporally
      associated with an increase in impedance to blood flow. This effect occurred to
      the same degree in both normal and abnormal groups, but in the abnormal group the
      already impaired blood flow to the intervillous space was further diminished,
      resulting in absence of forward flow in diastole. Such acute reductions of flow
      in response to frequent, impalpable uterine contractions may cause a prolonged
      and silent insult to uteroplacental perfusion, which could hasten fetal
      compromise. This effect appeared to be abolished in patients on nifedipine,
      suggesting a possible therapeutic role for this drug in uteroplacental
      insufficiency.

PMID- 12797103
TI  - The characterization of uterine tumors by transvaginal color Doppler.
AB  - The present study aimed to evaluate the possibility of using transvaginal color
      Doppler and spectral analysis to differentiate between malignant and benign
      uterine tumors. This method was performed on 308 patients with uterine tumors
      before gynecological surgery. The final diagnosis was made following pathological
      examination of the uterus. There were 291 benign and 17 malignant uterine tumors.
      Tumor arterial blood flow was detected in 134 (58%) patients with myoma (RI =
      0.58 +/- 0.12 SD), 23 (42.6%) patients with adenomyosis (RI = 0.67 +/- 0.14), 12
      (92.3%) patients with endometrial carcinoma (RI = 0.34 +/- 0.05)) three (100%)
      patients with uterine sarcoma (RI = 0.31 +/- 0.03) and in one case (100%) of
      sarcoma botryoides (RI = 0.33). Blood flow was not detected in patients with
      endometriotic cysts (n = 6). The comparison of RI between patients with uterine
      myoma and endometrial cancer showed a significantly lower RI in the cases of
      endometrial carcinoma (t = 13.5; p < 0.01). Our results showed that transvaginal
      color Doppler has potential in the non-invasive differentiation of benign and
      malignant uterine tumors.

PMID- 12797104
TI  - Intrafollicular blood flow during human ovulation.
AB  - Transvaginal ultrasonography with color flow mapping has been used to study
      changes in intrafollicular blood flow and morphology during follicular rupture
      and presumed ovulation in one human volunteer. Detailed monitoring started on day
      11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13.
      This event was preceded by a defined rise and peak in the level of immunoreactive
      serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood
      vessels were clearly visible in the inner ring of the follicle (the granulosa
      layer) at the time of the LH peak and part of the granulosa (probably containing
      the oocyte) started to detach before the follicle ruptured. The maximum value for
      the peak blood velocity in the inner vessels was observed 10 s after the start of
      follicular rupture and there was a concurrent increase in the impedance to blood
      flow, as reflected by the resistance index and the pulsatility index. The
      follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form
      about 1 min later. These preliminary data suggest that intrafollicular
      angiogenesis and changes in blood flow can be monitored by a relatively non
      invasive technique. Changes in vascularity might be used to predict imminent
      ovulation and could possibly be identified or modified biochemically to help
      achieve or avoid a pregnancy.

PMID- 12797105
TI  - Conservative management of pelvic abscess in recurrent pelvic inflammatory
      disease.
AB  - The recent incidence of acute-on-chronic pelvic inflammatory disease, with
      associated abscess formation, has dramatically increased. Recurrent abscess
      formation in chronic pelvic inflammatory disease that fails to respond to maximal
      antibiotic treatment has been traditionally treated by open surgical drainage,
      frequently accompanied by pelvic clearance.With the development of techniques
      associated with in vitro fertilization, treatment can now be effected allowing
      conservation of fertility. This paper describes 12 cases of ultrasound-directed
      transvaginal fine-needle aspiration of pelvic abscess. A positive outcome
      occurred in all patients, thus avoiding major surgery.

PMID- 12797106
TI  - Endovaginal ultrasound scanning to identify bladder tumors as the source of
      vaginal bleeding in postmenopausal women.
AB  - The increasing frequency of bladder tumors with increasing age is well
      documented, but the incidence of bladder tumors in a subgroup at potential risk,
      i.e. women with postmenopausal bleeding, is, however, not known. In a prospective
      study of 400 women with postmenopausal bleeding, endovaginal scanning (EVS) was
      performed the day before planned dilatation and curettage (D & C). Five bladder
      tumors were identified. For comparison, the medical records of 4500 women
      admitted for D & C due to postmenopausal bleeding, during a 15-year period, were
      reviewed. These women were not examined by ultrasound preoperatively. Eight
      bladder tumors were found in these women. The number of bladder tumors found in
      women with postmenopausal bleeding was high, especially in the group of women
      that underwent endovaginal ultrasound, compared to the known incidence
      (25/100,000 women) in this age group. On the basis of the present data, it
      appears evident that EVS contributes to an early detection of bladder tumors. We
      emphasize the importance of scanning all women with postmenopausal bleeding with
      endovaginal ultrasound.

PMID- 12797107
TI  - Prenatal sonography of autosomal trisomies.

PMID- 12797110
TI  - Adenovirus endocytosis.
AB  - Pathogen entry into cells occurs by direct penetration of the plasma membrane,
      clathrin-mediated endocytosis, caveolar endocytosis, pinocytosis or
      macropinocytosis. For a particular agent, the infectious pathways are typically
      restricted, reflecting a tight relationship with the host. Here, we survey the
      uptake process of human adenovirus (Ad) type 2 and 5 and integrate it into the
      cell biology of endocytosis. Ad2 and Ad5 naturally infect respiratory epithelial
      cells. They bind to a primary receptor, the coxsackie virus B Ad receptor (CAR).
      The CAR-docked particles activate integrin coreceptors and this triggers a
      variety of cell responses, including endocytosis. Ad2/Ad5 endocytosis is clathrin
      mediated and involves the large GTPase dynamin and the adaptor protein 2. A
      second endocytic process is induced simultaneously with viral uptake,
      macropinocytosis. Together, these pathways are associated with viral infection.
      Macropinocytosis requires integrins, F-actin, protein kinase C and small G
      proteins of the Rho family, but not dynamin. Macropinocytosis per se is not
      required for viral uptake into epithelial cells, but it appears to be a
      productive entry pathway of Ad artificially targeted to the high-affinity Fcgamma
      receptor CD64 of hematopoietic cells lacking CAR. In epithelial and hematopoietic
      cells, the macropinosomal contents are released to the cytosol. This requires
      viral signalling from the surface and coincides with particle escape from
      endosomes and infection. It emerges that incoming Ad2 and Ad5 distinctly modulate
      the endocytic trafficking and disrupt selective cellular compartments. These
      features can be exploited for effective artificial targeting of Ad vectors to
      cell types of interest.

PMID- 12797111
TI  - Augmented antitumor activity of a secondary lymphoid-tissue chemokine (SLC)
      interleukin (IL) 2 fusion protein in mouse.
AB  - BACKGROUND: To enhance the antitumor efficacy of IL2 gene therapy, combinations
      of several other genes, such as p53, a tumor suppressor gene, or lymphotactin, a
      C-chemokine, and the IL2 gene are attempted, and synergistic effects are
      observed. We report here on the enhanced antitumor activity of a fusion protein
      (mSLC-IL2) comprised of a newly identified member of the CC-chemokine family,
      mouse SLC (mSLC), and mouse IL2 (mIL2). METHODS: We constructed mSLC-IL2 by
      connecting the N-terminus of mIL-2 to the C-terminus of mSLC using a two-amino
      acid linker. The resultant fusion protein retained both mIL2 activity, as
      measured in a standard proliferation assay using a mouse IL-2 dependent cell
      line, and chemokine activity, as measured in a chemotaxis assay using a preB cell
      line expressing mSLC-specific receptor, CCR7. The gene encoding mSLC-IL2 was
      retrovirally transduced into fibroblast CL.7 cells, derived from Balb/c mice.
      RESULTS: Intradermal transplantation of fibroblasts expressing mSLC-IL2 into
      syngenic mice induced a dense accumulation of CD4(+) and CD8(+) cells at the
      sites of transplantation. Moreover, when CT-26 cells, derived from colon
      adenocarcinoma cells, were co-transplanted with mSLC-IL2-transduced fibroblasts,
      the CT-26 cell exhibited significantly lower tumorigenicity than CT-26 cells co
      transplanted with mIL2-transduced fibroblasts. CONCLUSIONS: These findings,
      obtained from both in vitro and in vivo data, suggest that the gene encoding mSLC
      IL2 may be a good candidate for inclusion as part of an anticancer gene therapy
      protocol.

PMID- 12797112
TI  - Aspartylglucosaminidase (AGA) is efficiently produced and endocytosed by glial
      cells: implication for the therapy of a lysosomal storage disorder.
AB  - BACKGROUND: Aspartylglucosaminuria (AGU) represents diseases affecting the
      central nervous system and is caused by a deficiency of a lysosomal enzyme,
      aspartylglucosaminidase (AGA). AGA, like lysosomal enzymes in general, are good
      targets for gene therapy since they move from cell to cell using the mannose-6
      phosphate receptor. Consequently, only a minority of target cells need to be
      corrected. Here, we wanted to determine which cell type, neurons or glia would
      better produce AGA to be transported to adjacent cells for use in possible
      treatment strategies. METHODS: Adenoviruses containing tissue-specific glial
      fibrillary acidic protein (GFAP) promoter and neuron-specific enolase (NSE)
      promoter were generated to target expression of AGA in Aga-deficient mouse
      primary glial and neuronal cell cultures. In addition an endogenous AGA promoter
      was used. The experimental design was planned to measure the enzymatic activities
      in the cells and media of neurons and glia infected with each specific virus. The
      endocytosis of AGA was analyzed by incubating neuronal and glial cells with media
      produced by each virus-cell combination. RESULTS: AGA promoter was shown to be a
      very powerful glia promoter producing 32 times higher specific AGA activity in
      glia than in neurons. GFAP and NSE promoters also produced a clear overexpression
      of AGA in glia and neurons, respectively. Interestingly, both the NSE and GFAP
      promoters were not cell-specific in our system. The amount of exocytosed AGA was
      significantly higher in glial cells than neurons and glial cells were also found
      to have a greater capacity to endocytose AGA. CONCLUSIONS: These data indicate
      the importance of glial cells in the expression and transport of AGA.
      Subsequently, new approaches can be developed for therapeutic intervention.

PMID- 12797113
TI  - Effects of adenovirus-mediated SV5 fusogenic glycoprotein expression on tumor
      cells.
AB  - BACKGROUND: The fusogenic (F) membrane glycoprotein of the paramyxovirus SV5
      allows virus to enter host cells and mediates fusion between neighboring cells,
      which leads to cell death. F glycoprotein is synthesized as an inactive precursor
      (F(0)) that is cleaved by cellular protease furine to form the active heterodimer
      F(1) + F(2). The active protein can induce syncytium formation in the absence of
      another integral glycoprotein (HN), a property that appears to be unique among
      paramyxoviruses. METHODOLOGY: We constructed a non-replicative adenovirus to
      express SV5 F protein in tumor cells, and its fusion capacity was analyzed by
      fluorescent and confocal microscopy. Cell viability and bystander effect were
      compared with the thymidine kinase/ganciclovir suicide gene therapy. The
      structure of F-expressing cells was studied using electron microscopy. RESULTS: F
      glycoprotein expression induced syncytium formation to a maximum at 72 h, after
      which syncytia progressively lost viability and detached. The cell membrane was
      disrupted while nuclear structure was preserved. Over-expression of SV5 F protein
      in tumor cells led to high cytotoxicity comparable with that associated with the
      thymidine kinase/ganciclovir. A potent bystander killing effect was detected
      until the ratio of F-transduced to non-transduced cells was 1 : 100. CONCLUSIONS:
      These results indicate that the fusogenic glycoprotein of the paramyxovirus SV5
      could be used to eliminate tumor cells and may encourage studies aimed at
      modifying its selectivity and combining its expression with other cytotoxic
      strategies to improve their efficacy.

PMID- 12797114
TI  - Sustained tetracycline-regulated transgene expression in vivo in rat retinal
      ganglion cells using a single type 2 adeno-associated viral vector.
AB  - BACKGROUND: Viral vector delivery of neurotrophic-expressing transgenes in the
      retina may retard or prevent the onset of blindness associated with photoreceptor
      degeneration. A key safety issue is to achieve regulated expression of these
      genes in the retina. The purpose of our study was to evaluate whether a single
      recombinant AAV-2 (rAAV) encoding for a tetracycline (Tet)-regulated destabilized
      reporter gene could provide quantitative profiles of gene regulation targeted to
      the rat neuroretina. METHODS: A rAAV vector carrying a destabilized green
      fluorescent protein (dgfp) under a tet-regulatable promoter and the tetracycline
      repressed transactivator (tTA) was generated (rAAVtetoff.dgfp) and administered
      intravitreally in nine Wistar rats. Retinas were monitored for 6 months using
      noninvasive fluorescence imaging and the animals were subjected to two cycles of
      doxycycline (Dox), a tetracycline analog. Eyes were ultimately examined by
      histology. RESULTS: Intravitreal injection of rAAVtetoff.dgfp resulted in
      effective transduction of ganglion cells. Following full expression of the
      transgene in the absence of Dox, 95% of the GFP signal was shut down 48 h post
      Dox administration and the signal was undetectable 7 days later. Initial levels
      of GFP expression were restored 21 days after Dox administration ceased. This
      pattern of expression was repeated twice over a period of 6 months. CONCLUSIONS:
      This report demonstrates that rAAVtetoff.dgfp intravitreally injected rats
      displayed tight and sustained long-term regulation of the reporter gene in
      ganglion cells. These findings may have important implications regarding rAAV
      mediated gene therapy using neuroprotective approaches for retinitis pigmentosa
      and glaucoma.

PMID- 12797115
TI  - Sustained transgene expression in cartilage defects in vivo after transplantation
      of articular chondrocytes modified by lipid-mediated gene transfer in a gel
      suspension delivery system.
AB  - BACKGROUND: Genetically modified chondrocytes may be able to modulate articular
      cartilage repair. To date, transplantation of modified chondrocytes into
      cartilage defects has been restricted to viral vectors. We tested the hypothesis
      that a recombinant gene can be delivered to sites of cartilage damage in vivo
      using chondrocytes transfected by a lipid-mediated gene transfer method. METHODS:
      Isolated lapine articular chondrocytes were transfected with an expression
      plasmid vector carrying the P. pyralis luciferase gene using the reagent FuGENE
      6. Transfected chondrocytes were encapsulated in alginate spheres and implanted
      into osteochondral defects in the knee joints of rabbits. RESULTS: In vitro,
      luciferase activity in pCMVLuc-transfected spheres showed an early peak at day 2
      post-transfection and remained elevated at day 32, the longest time point
      evaluated. The number of viable chondrocytes in non-transfected and transfected
      spheres increased over the period of cultivation. In vivo, luciferase activity
      was maximal at day 5 post-transfection, declined by day 16, but was still present
      at day 32. On histological analysis, the alginate-chondrocyte spheres filled the
      cartilage defects and were surrounded by a fibrous repair tissue composed of
      spindle-shaped cells. CONCLUSIONS: These data demonstrate the successful
      introduction of articular chondrocytes modified by lipid-mediated gene transfer
      in a gel suspension delivery system into osteochondral defects and the sustained
      expression of the transgene in vivo. This method may be used to define the
      effects of genes involved in cartilage repair and may provide alternative
      treatments for articular cartilage defects.

PMID- 12797116
TI  - Electroporation-mediated ex vivo gene transfer into graft not requiring injection
      pressure in orthotopic liver transplantation.
AB  - BACKGROUND: We investigated optimum conditions for ex vivo gene transfer into
      liver grafts by plasmid injection via the portal vein combined with
      electroporation in rat liver transplantation. METHODS: Anesthetized 9-week-old
      male Shionogi-Wistar rats were used as donors and recipients. After harvest of
      the liver graft from the donor rat, a tapered 3Fr. catheter was inserted into the
      portal vein of the liver graft ex vivo. After clamping the afferent vessels
      around the right and caudal liver lobes, pCAGGS-luciferase, which was diluted
      with one of several osmotic pressure solutions, or pCAGGS-green fluorescence
      protein (GFP) plasmid was injected into these lobes to keep the efferent vessels
      patent. Electrical pulses were applied to the liver graft during cold
      preservation in lactated Ringer's solution, University of Wisconsin solution, and
      histidine-tryptophan-ketoglutarate solution. RESULTS: Transfection efficacy was
      estimated by measurement of luciferase activity. Luciferase activity in the liver
      was dependent on both the voltage and electric current of the electrical pulse,
      and also on the type of preservation solution and plasmid osmotic pressure.
      Luciferase activity was noted only in plasmid-injected lobes of the liver graft.
      GFP-transfected cells were identified by GFP fluorescence. GFP was observed
      predominantly in perivascular cells, including hepatocytes. CONCLUSIONS: We have
      demonstrated successful ex vivo gene transfection into liver grafts without
      injection pressure by using a non-viral method.

PMID- 12797117
TI  - Target selection for antisense oligonucleotide induced exon skipping in the
      dystrophin gene.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle
      wasting disorder characterised by the absence of the protein dystrophin.
      Antisense oligonucleotides have been used to re-direct dystrophin pre-mRNA
      processing by blocking sequences crucial to pre-mRNA splicing, thereby inducing
      skipping of specific exons. We wished to determine which splicing motifs are most
      amenable as targets for antisense oligonucleotide induction of efficient and
      specific skipping of selected exons. METHODS: Antisense oligonucleotides were
      directed at regions of dystrophin exon 19 involved in pre-mRNA splicing,
      including the donor and acceptor splice sites and the exon splicing enhancer
      (ESE). Cultured myotubes were transfected with antisense oligonucleotides at
      various concentrations and studies undertaken to determine both specificity and
      efficiency of induced exon 19 skipping. RESULTS: Antisense oligonucleotides as
      small as 12 nucleotides targeting the ESE induced consistent and specific
      skipping of only exon 19 in both human and normal and mdx mouse myotubes.
      Antisense oligonucleotides directed at the donor and acceptor splice sites also
      induced specific exon 19 skipping while mismatched antisense oligonucleotides
      could only induce skipping when delivered at higher concentrations. No other
      dystrophin exons were removed from the mature mRNA as a consequence of these
      antisense oligonucleotides treatments. CONCLUSIONS: Antisense oligonucleotides
      directed at the ESE tended to be marginally more efficient than those which
      targeted the donor or acceptor splice sites, based on their ability to induce
      specific skipping at lower concentrations. The specificity of exon removal does
      not appear to be a function of target selection, but may reflect the combination
      of the splicing motifs and position of that exon in the pre-mRNA.

PMID- 12797120
TI  - Fetal cardiology.

PMID- 12797118
TI  - Antisense downregulation of mutant huntingtin in a cell model.
AB  - BACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder
      which is caused by an expansion of a CAG repeat sequence in the HD gene. The
      repeat encodes an expanded polyglutamine tract in the protein huntingtin. The
      still unknown pathological mechanisms leading to death of specific neurons in the
      brains of HD patients correlate with the expression of mutant huntingtin.
      Therefore, we have studied whether mutant huntingtin expression can be
      downregulated by antisense technique. METHODS: NT2 precursor cells and
      differentiated postmitotic NT2-N neurons, respectively, were transfected with
      plasmid constructs containing exon 1 of the HD gene with expanded CAG repeats in
      frame with the reporter protein EGFP. The transfected cell cultures were treated
      with a phosphorothioated antisense oligonucleotide (PS-ASHD/20+) or a control
      oligonucleotide either by cotransfection or by addition to the culture medium.
      RESULTS: Expression of the fusion protein containing the mutant huntingtin
      fragment resulted in diffuse green fluorescence in the cytoplasm and formation of
      aggregates in some of the NT2 cells and NT2-N neurons. We obtained antisense
      sequence-specific inhibition of expression of the fusion protein and/or
      suppression of the aggregate formation in both cell types. In the NT2 cells the
      antisense effect was dependent on the way of administration of the oligo.
      CONCLUSIONS: The PS-antisense oligo is effective in downregulation of mutant
      huntingtin, and the reduction of aggregate formation is a sensitive biological
      marker. The findings suggest that antisense knockdown of huntingtin could be a
      useful strategy for treatment of HD, and could also be suitable for studies of
      the normal and pathological function of huntingtin in different cellular model
      systems.

PMID- 12797121
TI  - Choroid plexus cysts: the need for further study.

PMID- 12797122
TI  - Teratogen exposure.

PMID- 12797123
TI  - Significance of sonographically detected second-trimester choroid plexus cysts: a
      series of 211 cases and a review of the literature.
AB  - A retrospective analysis of all fetuses with prenatally detected choroid plexus
      cysts, identified at our institution between 1988 and 1993, was performed.
      Cytogenetic data, associated sonographic findings, obstetric outcome and
      pediatric follow-up was obtained to determine the incidence of aneuploidy and the
      rate of associated congenital anomalies in second-trimester fetuses with this
      finding. There were 211 second-trimester fetuses identified with a choroid plexus
      cyst. Amniocentesis was performed in 175 (83%) and postnatal chromosome analysis
      was performed in one newborn. Follow-up data are available on 203 (96%). Of the
      176 cytogenetically studied fetuses, eight (4.5%) were aneuploid (including four
      cases of trisomy 18). In four of the aneuploid fetuses, the choroid plexus cyst
      was the only abnormal sonographic finding identified (including one case of
      trisomy 18). From this study and a review of the literature, we confirm that
      choroid plexus cysts are a sonographic marker for trisomy 18, even when
      identified as an isolated finding in an otherwise normal-appearing fetus. We
      conclude that the detection of a choroid plexus cyst merits further careful
      evaluation of fetal anatomy and consideration of cytogenetic evaluation.

PMID- 12797124
TI  - Teratogen exposure: lack of morphological abnormalities by detailed fetal
      sonography.
AB  - Teratogen exposures cause 1-2% of congenital abnormalities. Our anecdotal
      experience was that detailed fetal sonograms conducted for the indication of
      teratogen exposure failed to demonstrate significant morphological abnormalities.
      We reviewed our experience to see how often such examinations yielded positive
      results. Records from 11 September 1989 to 13 September 1993 were reviewed. All
      women referred for detailed fetal sonography for the sole indication of exposure
      to drugs, toxins, or infectious agents and with a sonographic age of 16-24
      menstrual weeks were included. All exposures were included in the study, even
      those without known teratogenic potential. Patients previously diagnosed with a
      morphological abnormality or with an abnormal level of maternal serum alpha
      fetoprotein were excluded.A total of 125 women with 126 singleton pregnancies
      comprised the study population. Ten women had multiple exposures. Including the
      multiple exposures, there was a total of 138 exposures, 104 to drugs and other
      toxins (45 of which were not known human teratogens), and 34 to infections. The
      only significant morphological abnormality found was a duplicated kidney in a
      woman with parvovirus exposure. While parvovirus is a cause of anemia and
      hydrops, it is not a known human teratogen. We therefore assume that this was a
      coincidental association. We conclude that teratogen exposure is a low-yield
      indication for detailed fetal sonography.

PMID- 12797125
TI  - Estimation of gestational age by transvaginal sonographic measurement of greatest
      embryonic length in dated human embryos.
AB  - A prospective descriptive study was carried out to establish reference values for
      gestational age assessment in the first trimester by measuring embryonic length
      in dated human embryos, by using transvaginal ultrasound. In 160 pregnant women
      who had undergone assisted reproductive procedures, 139 singleton embryos and 46
      embryos from 21 multiple pregnancies were studied between the 35th and 98th day
      after the last menstrual period. Transvaginal ultrasound examination, including
      inspection of embryonic structures and measurement of greatest embryonic length
      (L), was performed in these women. Estimation of gestational age (t) by
      measurement of L in singletons is best described by the equation t = 35.72 +
      1.082L(1)/(2) + 1.472L - 0.09749L(3)/(2). Mean 95% confidence interval and 95%
      prediction interval were 4.3 and 9.3 days, respectively. There was no significant
      change in the estimation curve when multiple measurements in singletons were
      taken nor when embryos from multiple pregnancies were measured. Accuracy of
      embryonic age estimation from a single measurement of greatest embryonic length
      was evaluated.

PMID- 12797126
TI  - Color Doppler examination of the outflow tracts of the fetal heart: a technique
      for identification of cardiovascular malformations.
AB  - The objective was to describe a technique using color Doppler to identify the
      outflow tracts of the fetal heart by directing the ultrasound transversely
      through the fetal chest. One hundred second- and third-trimester control fetuses
      were examined with real-time and color Doppler ultrasound. The ultrasound beam
      was directed cephalad, in the same transverse plane used to image the four
      chamber view, and the outflow tracts were examined. Four fetuses with abnormal
      cardiovascular anatomy were examined using the above approach, to study the
      anatomical relationships of the outflow tracts identified with color Doppler
      ultrasound in normal fetuses. When the ultrasound beam was directed immediately
      cephalad to the four-chamber view, the aorta was identified as it exited the left
      ventricle. Further movement of the ultrasound beam cephalad identified the
      following vessels in a single plane: the main pulmonary artery perpendicular to
      the ascending aorta; the left pulmonary artery branching from the main pulmonary
      artery; the full length of the ductus arteriosus; and the transverse arch of the
      aorta. The ascending aorta, main pulmonary artery, ductus arteriosus and
      transverse aortic arch were identified in 100% of fetuses. Four fetuses with
      abnormalities of the outflow tracts (aortic stenosis, aortic regurgitation,
      pulmonary stenosis and premature constriction of the ductus arteriosus) were
      imaged using this approach in which pathology was readily identified. This
      technique enables rapid identification of the outflow tracts in second- and third
      trimester fetuses using color Doppler and accurately identifies abnormalities of
      these vessels.

PMID- 12797127
TI  - Maternal hyperoxygenation in the treatment of mild intrauterine growth
      retardation: a pilot study.
AB  - The aim of this study was to determine the efficacy of long-term maternal
      hyperoxygenation in comparison with bed rest in the management of mildly growth
      retarded fetuses (5-10th centile).Thirty-eight patients with intrauterine growth
      retardation were studied. The patients were divided into oxygen-treated (n = 18)
      and untreated (n = 20) groups. Ultrasound assessment of amniotic fluid volume was
      performed on alternate days, and the fetal abdominal circumference was evaluated
      weekly. Doppler analysis of fetal/maternal circulation was performed upon the
      patient's arrival at hospital, after 12 h, and thereafter on alternate days until
      parturition. Fetal blood was sampled by cordocentesis for immediate blood gas
      analysis at the start of the study and on the day of delivery. Although in the
      treated patients there was significant improvement in Doppler flow pat tern and
      blood gas indices, no significant differences in type of delivery and perinatal
      outcome were noted between the groups. Maternal hyperoxygenation in mild
      intrauterine growth retardation did not improve perinatal outcome.

PMID- 12797128
TI  - The interpretation of uterine artery pulsatility index in normal and hypertensive
      pregnancy.
AB  - The Doppler flow velocity pulsatility index (PI) of the uteroplacental vascular
      bed is of debatable value for the interpretation of hemodynamic changes, when
      these are due both to pathological alterations in the vasculature, as in mild pre
      eclampsia, and to physiological adjustments to vasoactive substances. The aim of
      this study was to apply a mathematical model, which includes maternal pulse
      pressure and mean arterial pressure, to the PI and to investigate whether this
      formula would add information with respect to discrimination between normal women
      and those with mild or severe pre-eclampsia. The subjects were patients with mild
      (n = 41) and severe (n = 34) pre-eclampsia and, as a control group, healthy
      pregnant women (n = 46). The uterine artery PI was studied by spectral Doppler
      analyses and compared to a P(z) value, theoretically representing a 'back
      pressure' in the uteroplacental circulation. Additionally, P(z) values were
      computed from earlier data concerning the dynamic circulatory effects of
      dihydralazine and acute volume expansion. The basal PI was significantly higher
      in the severely pre-eclamptic patients but not in the mildly pre-eclamptic
      patients compared to the controls. However, the P(z) was significantly higher in
      patients with both mild (p < 0.001) and severe pre-eclampsia (p < 0.0001)
      compared to the normal group. In the severely pre-eclamptic patients receiving
      dihydralazine, the P(z) tended to decrease (p = 0.07), in contrast to the volume
      expansion group where P(z) was unaffected by the procedure. In conclusion, it
      seems that including measurement of the mean arterial pressure and pulse pressure
      with the PI adds valuable information about the circulatory status in this
      particular vasculature, regarding both 'basal' values and hemodynamic changes.

PMID- 12797129
TI  - Effect of standing on non-pregnant uterine blood flow.
AB  - Uterine artery blood flow measurements made solely in the recumbent position may
      miss physiological changes that occur while patients are upright. We evaluated
      the effect of standing on the minute blood flow volume of the ascending uterine
      artery, the pulsatility index (PI), resistance index (RI) and waveforms and on
      the PI and RI of the myometrial spiral arteries and waveforms at 3-8 and at 9-14
      min standing in 74 non-pregnant women. At 9-14 min, the uterine artery blood flow
      volume had decreased by an average of 34% and the RI had significantly increased
      in 70% of subjects. Decreased uterine artery blood flow volume was associated
      with increased distal resistance and with decreased vessel diameter, possibly due
      to stretching or kinking of the uterine arteries. Changes in the spiral artery PI
      paralleled changes in the uterine artery PI at 9-14 min, but were less
      pronounced. Spiral artery PI and RI were not related to the uterine artery blood
      flow volume while women were recumbent, although they were significantly related
      while women were standing. The effects of age, uterine mobility and uterine
      position on uterine artery or spiral artery blood flow were apparent only while
      women were standing. We conclude that standing as well as recumbent studies are
      necessary when uterine and myometrial blood flow are evaluated, and that uterine
      flow volume per minute should be measured whenever possible.

PMID- 12797130
TI  - Characteristics of follicular evacuation during human ovulation.
AB  - Our objectives were to determine the rate and extent of follicular evacuation
      during human ovulation. Female volunteers were given 5000 or 10,000 IU human
      chorionic gonadotropin to induce ovulation when a follicle reached 18-20 mm.
      Ovulations were observed via transvaginal ultrasonography and recorded. Images
      were digitized for computer-assisted analysis. Areas of the follicles, taken to
      reflect follicular volume, were measured at specific time intervals from the
      moment of the first leakage of fluid until complete follicular evacuation. Twenty
      five ovulations were visualized. In 23 cases (92%) all of the follicular fluid
      was expelled, but in two cases the follicle failed to empty completely. In all
      complete ovulations the initial fluid loss was rapid. The time to reach 70%
      evacuation was 0.9 +/- 0.3 min (+/- SEM). The remaining fluid leaked out more
      slowly; the mean time to complete follicular evacuation was 6.1 +/- 1.1 min.
      There was considerable variability in the rates of ovulation (range 6 s to 18.5
      min). An association was observed between the type of stigma formed prior to
      ovulation and the initial rate of fluid loss. The data provide evidence of
      variability during follicular evacuation, which may in turn influence the
      successful expulsion of the oocyte from the follicle.

PMID- 12797131
TI  - Use of transvaginal ultrasonography with color Doppler imaging to determine an
      appropriate treatment regimen for uterine fibroids with a GnRH agonist before
      surgery: a preliminary study.
AB  - The aim was to obtain data that could be used to determine the most appropriate
      treatment regimen for uterine fibroids with a gonadotropin releasing hormone
      analog (goserelin) before surgery. Fifteen premenopausal women (aged 27-53 years;
      mean 40 years) were referred from a gynecological outpatients' clinic. They all
      had uterine fibroids and were awaiting hysterectomy or myomectomy. All women were
      scheduled to receive an implant of goserelin (3.6 mg), undergo transvaginal
      ultrasonography and have a sample of peripheral blood taken at monthly intervals
      for 6 months. The main outcome measures were fibroid size and indices of blood
      flow (the pulsatility index and peak systolic velocity) in both uterine arteries
      and the principal artery supplying the largest fibroid. The concentrations of
      follicle stimulating hormone, estradiol, luteinizing hormone and progesterone
      were measured in peripheral plasma. Twelve women (80%) completed 2 months of
      treatment, but only three (20%) completed the study (due to side-effects of the
      drug). After 2 months of treatment, the plasma hormone levels were all in the low
      normal range; the mean fibroid volume had decreased by 53% and the mean peak
      systolic blood velocity in the fibroid artery had decreased by 45%. Mean changes
      in all indices were < 10% over the next 4 months of treatment. Six women (40%)
      had fibroids with an initial volume of > 100 ml; these tumors showed the largest
      reduction in size. We conclude that women with a uterine fibroid of > 100 ml are
      the best candidates for treatment with goserelin (3.6 mg/month) before surgery.
      Two months' treatment effects a marked reduction in fibroid volume and blood flow
      and is associated with good compliance.

PMID- 12797132
TI  - Subendometrial-myometrial contractility in conception and non-conception embryo
      transfer cycles.
AB  - This study describes the characteristics of subendometrial-myometrial
      contractions seen on transvaginal sonography on the day of embryo transfer in
      assisted conception cycles and their significance for pregnancy outcome.A total
      of 112 cycles were studied where three embryos with minimal or no fragmentation
      were transferred. Transvaginal sonography was performed just prior to embryo
      transfer. A sagittal view of the uterine cavity was obtained and the ultrasound
      probe was held steady for 2 min. The video recorded image was analyzed at normal,
      three and five times normal speed. The frequency (contractions/min), direction
      (fundally or cervically directed) and length (entire cavity or localized) of
      contractions were noted. Conception and non-conception cycles were compared by
      determining the standard error of difference between means and proportions and
      the confidence intervals. The mean frequencies of contractions in the conception
      and non-conception cycles were 2.09 (SD = 0.8) and 1.92 (SD = 0.85),
      respectively. A total of 57.6% of cycles in the conception group and 46% in the
      non-conception group had contractions directed towards the cervix. There was no
      statistically significant difference between the two groups in any of the
      parameters studied. However, when frozen embryo replacement cycles (n = 40) were
      studied separately, the incidences of fundally directed contractions were 28.6%
      and 66.7% in conception and non-conception cycles, respectively. This was
      statistically significant. Comparison of cycles resulting in miscarriage with
      those leading to pregnancies beyond 16 weeks revealed no statistical difference
      in the characteristics of the contractions. We concluded that subendometrial
      myometrial contractions studied on the day of embryo transfer (luteal day 2) do
      not predict the outcome in in vitro fertilization cycles.

PMID- 12797133
TI  - Early sonographic diagnosis of intrapericardial teratoma.
AB  - An intrapericardial teratoma associated with a large pleural effusion and
      elevated aortic outflow velocity was diagnosed at 23.6 weeks' gestation. Less
      than 4 weeks earlier, an obstetric scan, including a four-chamber heart view, had
      been normal. In less than a week following diagnosis, fetal hydrops and
      bradycardia developed. 'Heroic' pericardiocentesis was declined by the patient,
      and the fetus died. This case demonstrates the potential for rapid growth in
      pericardial teratomas, and illustrates the possibility of anticipating fetal
      compromise from tumor mass effect, when intracardiac Doppler studies are
      abnormal. Implications for management of these rare tumors, and specifically for
      the hypothetical role of fetal surgery, are discussed.

PMID- 12797134
TI  - Doppler velocimetry and the assessment of fetal well-being in normal and diabetic
      pregnancies.
AB  - Doppler ultrasound has been proposed as a useful addition to antepartum testing
      in high-risk pregnancies. Increased placental resistance has been associated with
      underlying placental vascular disease, as well as abnormal fetoplacental blood
      flow. Since pregnancies complicated by diabetes are at risk for these
      complications, the application of Doppler ultrasonography for such pregnancies
      has been evaluated by several investigators.Multiple investigations have examined
      the relationship between maternal blood glucose levels and abnormal Doppler
      waveforms in women with diabetes. Of the nine published studies, four found a
      correlation between Doppler indices and glucose control, as measured by mean
      blood glucose levels and glycosylated hemoglobin levels, while five did not.
      However, this apparent discrepancy may be explained by the fact that the majority
      of women studied were in good or excellent control, as this is currently the
      accepted standard of care. In fact, the one study performed in primarily non
      diabetic women demonstrated that increases in maternal plasma glucose
      concentrations of 30 mg/dl were followed by significant rises in the mean
      pulsatility index in both the umbilical and carotid arteries. More dramatic was
      the finding by most investigators that systolic/diastolic (S/D) ratios in third
      trimester umbilical arteries were elevated in women with evidence of diabetic
      microvascular disease. Elevated third-trimester S/D ratios were associated with
      adverse maternal and perinatal outcomes in these women, specifically pre
      eclampsia and intrauterine growth retardation. In conclusion, although elevated
      Doppler indices correlated with adverse outcomes in diabetic pregnancies, Doppler
      indices may be elevated in the otherwise uncomplicated diabetic patient with
      associated microvascular disease and with a normal outcome. Therefore, the
      Doppler ultrasound assessment of fetal well-being in diabetic pregnancies must be
      interpreted with caution.

PMID- 12797135
TI  - Congenital vascular anomalies of the umbilical cord: the value of color Doppler
      ultrasound in prenatal diagnosis.

PMID- 12797136
TI  - Assessment of tumor-induced angiogenesis by three-dimensional display: confusing
      Doppler signals in ovarian cancer screening?

PMID- 12797137
TI  - Obstetric and gynecological scanning in Israel.

PMID- 12797139
TI  - Screening for fetal chromosomal abnormalities: need to change the rules.

PMID- 12797140
TI  - New technologies in obstetrics and gynecology: the test of time.

PMID- 12797141
TI  - Should clinical decisions be made about ovarian masses using transvaginal color
      Doppler?

PMID- 12797142
TI  - Correlations in umbilical blood flow Doppler velocities in the human fetus during
      breathing.
AB  - We hypothesized that changes in intrathoracic pressure during fetal breathing
      episodes result in quantifiable variations in umbilical arterial and venous blood
      flow velocities, and that these variations are related to compliance properties
      of each system. We further hypothesized that these variations in velocities are
      different in fetuses with normal and abnormal umbilical arterial Doppler
      velocities. Umbilical arterial and venous Doppler velocities were measured
      simultaneously during breathing episodes in 15 normal fetuses and 14 fetuses with
      elevated systolic-to-diastolic (S/D) umbilical arterial Doppler velocity ratios.
      Umbilical arterial end-diastolic velocity changes were less than umbilical venous
      velocity changes in normal fetuses, but were significantly greater in four
      fetuses with elevated S/D ratios (p < 0.004). Furthermore, umbilical arterial
      diastolic velocity minima preceded umbilical venous velocity minima by a time lag
      that was greater in fetuses with elevated S/D ratios (p < 0.002). These results
      suggest that differences in umbilical arterial and venous velocity variation
      during fetal breathing episodes may be related in part to vascular compliance,
      which may be altered in fetuses with abnormal umbilical arterial Doppler
      velocity.

PMID- 12797143
TI  - The biophysical profile as a tool for prediction of preterm delivery.
AB  - Our objective was to determine if any of the following parameters is a predictor
      of preterm delivery: gestational age, cervical dilatation, or biophysical profile
      score.Sixty-two women with certain dates, intact membranes, and preterm
      contractions more frequent than 300 min underwent a 30-min ultrasonographic
      assessment of fetal breathing movements, fetal tone, fetal movement and amniotic
      fluid volume, each of which was scored as 0, 1, or 2 before any tocolytics were
      given. The total score (0-8) was calculated and cervical dilatation was recorded.
      All women were subsequently placed on tocolytics. Data were analyzed using
      survival analysis with stepwise regression of the covariates to determine the
      predictive values of the total score, its individual parameters, gestational age,
      and cervical dilatation to the outcome variable of hours to delivery. Gestational
      age, cervical dilatation and time interval to delivery were categorized and
      entered into a logistic regression model with the total score and its components
      to determine predictive odds.Total score (p < 0.0001) and cervical dilatation (p
      < 0.0001) were the most significant variables associated with time interval to
      delivery, followed by gestational age (p = 0.035). When the individual
      biophysical parameters were entered into the model, fetal tone (p < 0.0001),
      cervical dilatation (p < 0.0001) and gestational age (p < 0.014) were the only
      variables related to time interval to delivery. Predictive odds of delivery in
      less than 48 h in relation to fetal tone and cervical dilatation were calculated.
      Total score, fetal tone, and cervical dilatation were strongly associated with
      time interval to delivery. Our study did not support fetal breathing movements as
      a predictor of preterm delivery.

PMID- 12797144
TI  - Fetal cerebral blood flow velocity during labor and the early neonatal period.
AB  - This study was performed to elucidate circulatory changes in the fetal cerebral
      circulation during uncomplicated labor and in early neonatal life. Eighteen
      healthy term singleton fetuses were followed longitudinally during labor. Using
      the transabdominal approach, and the color Doppler technique, the middle cerebral
      artery was identified and Doppler flow velocity waveforms recorded between and
      during uterine contractions. Neonatal recordings were made by insonating the
      middle cerebral artery from the temporal region before and immediately after the
      cutting of the umbilical cord, and at 1 hour and 1 day after birth. The recorded
      Doppler signals were evaluated for pulsatility index, heart rate, peak systolic
      flow velocity, end-diastolic flow velocity and time-averaged maximum velocity.
      There was no change in the pulsatility index between and during contractions
      (1.39 +/- 0.36 and 1.40 +/- 0.39, respectively, mean +/- SD). A significant
      decrease in the pulsatility index compared to fetal values was seen 4 min after
      birth (1.06 +/- 0.30, p < 0.01). One hour after birth, the pulsatility index
      values increased significantly (1.52 +/- 0.25, p < 0.001), to fall again between
      I hour and 1 day after birth (0.95 +/- 0.26, p < 0.001). Mechanical compression
      of the skull, blood gas changes and a decrease in ductal shunting may all have
      contributed to these changes. The present study has shown physiological neonatal
      circulatory adaptation and onset of breathing to cause manifest changes in
      cerebral blood flow velocity.

PMID- 12797145
TI  - The role of Doppler velocimetry in the structurally normal second-trimester fetus
      with elevated levels of maternal serum alpha-fetoprotein.
AB  - Umbilical and uterine artery velocimetry was performed in 199 second-trimester
      pregnancies undergoing sonographic examination for unexplained elevated levels of
      maternal serum alpha-fetoprotein in order to evaluate the efficacy of Doppler
      waveforms for the prediction of adverse perinatal outcome. A total of 169
      pregnancies resulted in term deliveries of infants with appropriate growth for
      age, and 30 pregnancies (15%) had adverse outcomes, including preterm delivery,
      growth retardation and death. The umbilical artery systolic/diastolic ratio was
      not statistically different in the two groups (3.9 vs. 4.2, p = 0.16). The
      uterine artery systolic/diastolic ratio was slightly greater in the group with
      abnormal outcome (5.7) than in the group with normal outcome (3.3), but the
      difference was not significant (p = 0.11). Forty-six patients had uterine artery
      waveforms that exhibited an early diastolic notch. Of these, 31 had a grade 1
      notch in which the lowest part of the notch was not greater than one half of the
      diastolic frequency shift. Fifteen patients had a severe or grade II notch in
      which the deepest part of the diastolic notch was less than half of the diastolic
      flow. In patients with either no diastolic or grade I uterine artery notch, the
      incidence of adverse outcomes was 23/184 (12.5%). In patients with a grade II
      notch, 7/15 (47%) had a poor outcome. The rate of adverse outcome in patients
      with a grade II notch was more than three times that observed in women without
      severe uterine notch, yielding a relative risk of 3.4 (95% CI 1.9-6.0). Thus, the
      presence of a grade II uterine artery notch on second-trimester sonographic
      evaluation is associated with an increased risk for adverse perinatal outcome
      over unexplained elevated levels of maternal serum alpha-fetoprotein.

PMID- 12797146
TI  - Reference ranges for fetal venous and atrioventricular blood flow parameters.
AB  - This cross-sectional study establishes reference ranges with gestation for
      Doppler parameters of fetal venous and atrioventricular blood flow. Color flow
      Doppler was used to examine 143 normal singleton pregnancies at 20-40 weeks'
      gestation. Flow velocity waveforms were recorded from the ductus venosus, right
      hepatic vein and inferior vena cava. The waveforms are triphasic, reflecting
      ventricular systole, early diastole and atrial contraction. Peak velocities for
      these parameters were measured with pulsed Doppler and a new index, the peak
      velocity index for veins (PVIV), was calculated. Similarly, time-averaged maximum
      velocities for the whole cardiac cycle were measured and the pulsatility index
      for veins (PIV) was calculated. Flow velocity waveforms were also recorded at the
      level of the atrioventricular valves and the ratios of peak velocities at early
      diastolic filling (E) and atrial contraction (A) were calculated. Regression
      analysis was used to define the association of each measured and calculated
      Doppler parameter with gestational age. Blood flow velocities in the fetal veins
      and velocities and E/A ratios across the atrioventricular valves increased
      significantly with gestation, whereas PVIV and PIV decreased. Blood flow
      velocities were highest in the ductus venosus and lowest in the right hepatic
      vein, and PVIV and PIV were highest in the hepatic vein and lowest in the ductus
      venosus. In the ductus venosus, there was always forward flow throughout the
      heart cycle, whereas in the inferior vena cava and hepatic vein during atrial
      contraction, flow was away from or towards the heart or there was no flow.
      Pulsatility of flow velocity waveforms in the venous system is the consequence of
      changes in pressure difference between the venous system and the heart during the
      heart cycle. The finding that PVIV and PIV decrease with gestation is consistent
      with decreasing cardiac afterload and maturation of diastolic ventricular
      function.

PMID- 12797147
TI  - Color Doppler imaging of the uteroplacental circulation in the middle trimester:
      observations on the development of a low-resistance circulation.
AB  - We aimed to study the changes in the flow dynamics of the uteroplacental and
      umbilical circulations in the middle trimester of normal pregnancy, and establish
      normal ranges for indices of the Doppler flow velocity waveforms (FVWs) from both
      circulations at 14, 18 and 24 weeks. A longitudinal study was conducted with the
      use of color Doppler imaging to localize both uterine arteries and umbilical
      arteries and obtain FVWs from 106 healthy nulliparous women with a singleton
      pregnancy. Of these, 70 did not have a complicated pregnancy outcome, defined as
      hypertension, growth retardation, preterm delivery or perinatal death. We
      measured the resistance index (RI), pulsatility index (PI), systolic/diastolic
      (S/D) ratio and presence of early diastolic notching in both uterine arteries,
      and RI, PI and S/D in one umbilical artery. The results showed a fall in all
      measured indices of blood flow impedance in the uteroplacental and umbilical
      circulations and a marked reduction in the incidence of the early diastolic notch
      in the uterine artery FVWs during the mid-trimester. Our conclusion was that
      color Doppler imaging allows for the accurate localization of both uterine and
      umbilical arteries. Doppler FVWs then obtained confirm the development of the low
      resistance uteroplacental and umbilical circulations in the mid-trimester.
      Diastolic notching is common at 14 weeks in normal pregnancy but uncommon at 24
      weeks.

PMID- 12797148
TI  - Endoscopic laser coagulation of umbilical cord vessels in twin reversed arterial
      perfusion sequence.
AB  - In monozygotic twin pregnancies with reversed arterial perfusion (TRAP) sequence,
      the donor twin is ut high risk of perinatal death. This paper describes the use
      of endoscopic surgery in the management of this condition. In four cases of TRAP
      sequence presenting at 17, 20, 26 and 28 weeks' gestation, respectively, an
      endoscope was introduced into the uterus under local anesthesia and a Nd-YAG
      laser was used to coagulate the umbilical cord vessels of the acardiac twin.
      Laser coagulation was successful in arresting blood flow to the acardiac fetus in
      the cases treated at 17 and 20 weeks, and healthy infants were delivered at term.
      In the pregnancies treated at 26 and 28 weeks, the umbilical cords were very
      edematous and laser coagulation failed to arrest blood flow; healthy infants were
      delivered after spontaneous labor at 29 weeks. These findings suggest that,
      during mid-gestation, endoscopic laser coagulation of the umbilical cord vessels
      of the acardiac twin is an effective method of treating TRAP sequence. In later
      pregnancy, alternative methods of treatment are needed.

PMID- 12797149
TI  - Fetal umbilical cord ligation under ultrasound guidance.
AB  - In a patient with severe twin-to-twin transfusion syndrome, ultrasound-guided
      umbilical cord ligation of the hydropic recipient twin was performed at 27 weeks'
      gestation. The procedure was successful in arresting the blood flow and was
      associated with improvement in the condition of the severely compromised donor
      fetus. At 29 weeks' gestation, premature onset of labor occurred and a healthy
      baby was delivered by emergency Cesarean section. This report demonstrates the
      feasibility of ultrasound-guided cord ligation for selective feticide in a case
      of severe twin-to-twin transfusion syndrome.

PMID- 12797150
TI  - Use of an endolaparoscopic probe in conservative management of Fallopian
      pregnancy.
AB  - The incidence of extrauterine pregnancy has shown an increasing trend, exceeding
      one out of every 100 term pregnancies. This has resulted in the development of
      more and more conservative surgical treatments in order to retain the fertility
      of women. The use of operative laparoscopy has led to progress being made in this
      direction, due to reduced tissue trauma and a reduction in the number of
      peritoneal adhesions. Tubal isthmic pregnancies tend to cause an irregular
      increase in the size of the whole tube, which causes problems for pinpointing the
      exact site of the ectopic implantation. It is often necessary to make a
      longitudinal incision in the tubal wall to identify the chorionic tissue and
      remove it completely. In an attempt to avoid this unnecessarily extensive
      surgery, we used an echographic sector probe under laparoscopic control to locate
      the exact area of the ectopic implantation. We found it was possible to remove
      the villous tissue through a very short and precise cut in the tubal wall which
      facilitated the drainage of the lumen and reduced the bleeding normally
      associated with more extensive tubal surgery. Hysterosalpingographic follow-up
      studies after 2 months showed good tubal recanalization.

PMID- 12797151
TI  - Quantitative flow measurements for classification of ovarian tumors by
      transvaginal color Doppler sonography in postmenopausal patients.
AB  - Color Doppler and Duplex measurements were obtained in 83 (42 benign, 41
      malignant) ovarian tumors in postmenopausal patients. An ATL UM9/HDI was used.
      The following flow criteria were analyzed: lowest resistance index (RI) and
      pulsatility index (PI), total number of arteries and number of central arteries
      and the maximum, mean and sum of systolic, end-diastolic and time-averaged
      maximum velocities of all intratumoral vessels. In 98% of malignant and in 85% of
      benign lesions, vessels were detected. All flow criteria showed highly
      significant differences between benign and malignant tumors (p < 0.0001).
      However, there was a considerable overlap between benign and malignant tumors
      (e.g. the median of the lowest RI was 0.62 (range 0.26-1.0) for benign and 0.40
      (0.22-0.66) for malignant tumors; the median of the maximum systolic velocity was
      17.5 cm/s (range 5.2-61.5 cm/s) for benign and 47.05 cm/s (14.6-105.0 cm/s) for
      malignant tumors). Differentiation of malignant tumors by the lowest RI and PI,
      number of arteries and maximum of systolic flow velocities gave a sensitivity of
      77-85%, specificity of 77-83% and accuracy of 80-84%. Differentiation was
      superior by calculation of the maximum end-diastolic velocities and by the
      summation of the systolic, end-diastolic and time-averaged maximum flow
      velocities: sensitivity 90-9.5% specificity 83-86% and accuracy 87-91%. This
      study confirms that a single measurement is not sufficient for an accurate
      differentiation of ovarian lesions and, besides the measurement of minimum RI and
      PI, the measurements of flow velocities as Doppler criteria play an important
      role.

PMID- 12797152
TI  - Prevalence in a volunteer population of pelvic cancer detected with transvaginal
      ultrasound and color flow Doppler.
AB  - Our objective was to find the prevalence of non-symptomatic endometrial and
      ovarian neoplasms in a volunteer population of women, aged 40 and over. We
      offered a free volunteer screening program to asymptomatic women for a study
      using transvaginal ultrasound and color flow Doppler for the detection of pelvic
      cancer. In the first 2 years, 2117 women were examined, 51.3% post-menopausal. An
      ovarian cyst was defined as having a maximum diameter of more than 2.4 cm. Color
      flow was used to identify blood vessels feeding pelvic organs and adnexal
      enlargements. An abnormal Doppler flow velocity for the ovary was defined as a
      resistance index of less than 0.41. Ovarian cysts of less than 5 cm with normal
      Doppler indices were followed up in 6 months to 1 year. An adnexal morphology
      score was created to quantify the usefulness of this parameter, particularly in
      postmenopausal women. Indications for surgery were pre-defined as a persistent
      ovarian cyst of more than 5 cm, a persistent suspicious Doppler and a total
      endometrial thickness of greater than 0.59 cm in postmenopausal women not taking
      hormones.A total of 202 women (9.5%) had ovarian cysts. Fourteen women were
      operated upon because of size criteria, one because of family history and three
      for persistent abnormal flow. By Doppler study, 15 cysts were predicted to be
      benign and histology was confirmatory. There were two false positives and one
      true positive, a stage Ib ovarian cancer. There were no false negatives, although
      a stage I endometrioid cancer of the ovary was detected 8 months after a negative
      scan. In those cases in which follow-up data were available, 56% of the cysts
      regressed in premenopausal women. In postmenopausal women, 28% regressed. Twenty
      of 1086 postmenopausal women had endometrial biopsies. Three had endometrial
      cancer, two stage I and one stage IIA. Five had atypical or adenomatous
      hyperplasia, and seven had benign polyps. So many women have small asymptomatic
      cysts of the ovary that a major reorientation of physicians' attitudes towards
      the ovary will have to be introduced to adapt to this new information. In this
      population, the prevalence of benign epithelial ovarian neoplasms was 7/1000, and
      of malignancy was 05/1000. In postmenopausal women, the prevalence rate for
      endometrial cancer was 5/1000, with 5/1000 hyperplasias and 7/1000 benign polyps.
      When endometrial and ovarian cancer screening are combined, the yield is
      comparable to that seen in breast and cervical cancer screening.

PMID- 12797153
TI  - Blood flow velocity in the uterine and ovarian arteries during menstruation.
AB  - Eleven healthy women with regular menstrual cycles were examined with a
      combination of two-dimensional real-time ultrasound and color and spectral
      Doppler techniques on the 7th day after follicular rupture, and on the 1st, 2nd,
      3rd and 4th days of menstrual bleeding. Both uterine arteries, arteries in the
      stroma and hila of both ovaries, in the wall of the largest follicle of the non
      dominant ovary and in the wall of the corpus luteum were examined with the
      Doppler technique. The pulsatility index (PI) and the time-averaged maximum
      velocity were calculated. In the uterine arteries, the PI was highest on the
      first day of menstrual bleeding (median PI 3.2 for the dominant and 3.0 for the
      non-dominant uterine artery), after which it decreased to its lowest values on
      the second day (median PI 2.1 and 1.8, respectively) and third day (median PI 2.2
      and 2.1, respectively). The time-averaged maximum velocity reached its highest
      value on the second and third days of menstruation. The corpus luteum was still
      visible on the first day of menstrual bleeding in all women, and on the second
      day in five. It was indistinguishable on the third and fourth days of
      menstruation in all women. In the dominant ovary, the time-averaged maximum
      velocity of flow in the arteries in the ovarian hilum decreased during menstrual
      bleeding and was lower during menstruation than in the preceding luteal phase. In
      the non-dominant ovary, neither the PI nor the time-averaged maximum velocity
      manifested any consistent changes during the period studied. We conclude that
      substantial changes in PI and time-averaged maximum velocity occur in the uterine
      arteries and in the arteries of the dominant ovary during menstruation.

PMID- 12797154
TI  - Perineal bladder neck ultrasound: appearances before and after continence
      surgery.
AB  - An objective method of quantifying suture tension during bladder neck elevation
      for genuine stress incontinence has long been sought. Perineal ultrasonography
      has been used to measure bladder neck position and excursion in continent and
      incontinent women. This study used perineal ultrasound findings to determine
      surgical positioning of the bladder neck and predict outcome. Eighteen
      asymptomatic controls and 72 women with genuine stress incontinence were studied
      before and after continence surgery. Perineal ultrasonography was used to plot
      bladder neck position at rest and on maximum Valsalva maneuver on an x, y co
      ordinate system to allow comparison between groups. Logistic regression analysis
      was then performed to derive an equation for the likelihood of continence. In
      both pre-and postoperative analysis, the best correlation with continence was
      achieved with the use of the patient's age and the distance of the bladder neck
      resting position measured along the x-axis. An equation was derived to give the
      probability of continence. The equation is easily calculated using a pocket
      calculator. The distance of the bladder neck along the x-axis is under the direct
      control of the surgeon, so the patient's age can be put into the equation and the
      distance along the x-axis most likely to make the patient continent can be
      calculated. This can be done during surgery to provide an objective method for
      evaluating suture tension.

PMID- 12797156
TI  - Prenatal color Doppler diagnosis of placenta previa accreta.

PMID- 12797155
TI  - Strawberry-shaped skull in fetal thanatophoric dysplasia.
AB  - The sonographic finding of a strawberry-shaped skull is a marker of serious fetal
      malformation, most commonly associated with trisomy 18. We report a novel
      association of this sign with thanatophoric dysplasia.

PMID- 12797157
TI  - Umbilical cord pseudocyst in trisomy 13.

PMID- 12797158
TI  - Ultrasound as a screening test for neural tube defects (and other important
      anomalies).

PMID- 12797159
TI  - The role of venous Doppler in fetuses with non-immune hydrops.

PMID- 12797160
TI  - Extracardiac anomalies, aneuploidy and growth retardation in 100 consecutive
      fetal congenital heart defects.
AB  - The importance of extracardiac anomalies in 100 consecutive fetuses with
      congenital heart disease was evaluated. The most common cardiac diagnoses were
      hypoplastic left heart syndrome in 35% and atrioventricular canal defect in 15%.
      Extracardiac anomalies were present in 42%, abnormal karyotype in 19% and
      intrauterine growth retardation in 20%. There were 45 survivors (35 required
      neonatal surgery, ten did not require early surgery) and 80% (36/45) of the
      survivors had isolated congenital heart disease. Extracardiac anomalies and
      abnormal karyotype were more frequently present in non-survivors (p < 0.001).
      Also, intrauterine growth retardation was more frequent in non-survivors (p <
      0.05).

PMID- 12797161
TI  - Doppler in non-immune hydrops fetalis.
AB  - Fetal ultrasound studies were performed on 24 fetuses with non-immune hydrops to
      evaluate echocardiographic and cardiovascular Doppler parameters that may be
      useful in assessing hemodynamics and in predicting outcome. Of all cardiovascular
      parameters analyzed, only the presence of abnormal pulsations in the umbilical
      vein (p < 0.001) was found to be significantly different between the 11 survivors
      and 13 non-survivors. In a smaller subset of 12 fetuses, in whom inferior vena
      caval waveforms were recorded, survivors (n = 6) had a significantly lower
      percentage of retrograde flow in the inferior vena cava (p < 0.001) and higher
      inferior vena caval E/V velocity ratio (p < 0.001) than non-survivors (n = 6).
      Sixteen of the 24 cases examined had abnormal umbilical venous pulsations; 12 of
      the 16 (75%) died including all fetuses with hydrops due to twin-to-twin
      transfusion or congenital heart disease. When fetuses with pulsatile flow in the
      umbilical vein were compared with fetuses with normal umbilical venous flow, the
      following significant differences were found: lower right and left ventricular
      output velocities, larger inferior vena caval diameter, decreased shortening
      fractions of the right and left ventricles, and lower peak velocities at the
      aortic and pulmonary valves and in the ductus arteriosus.

PMID- 12797162
TI  - First-trimester uteroplacental and fetal blood flow velocity waveforms in
      normally developing fetuses: a longitudinal study.
AB  - Our objectives were to obtain a complete overview of uteroplacental and fetal
      hemodynamics early in pregnancy and to record flow velocity waveforms in the
      vitelline artery using color Doppler equipment. Flow velocity waveforms were
      recorded in 18 uneventful pregnancies between 6 and 16 weeks of gestation.
      Doppler recordings were made of the left and right uterine and spiral arteries
      from 6 weeks of gestation onwards. Recordings of c the umbilical artery, fetal
      aorta and fetal cerebral arteries started in weeks 7, 8 and 9, respectively.
      Where possible, the vitelline arteries were also recorded. The resistance and
      pulsatility indices and 95% confidence intervals for predictions were
      calculated.For the uterine and spiral arteries, characteristics of the waveforms
      were assessed. The resistance index of both uterine and spiral arteries gradually
      decreased with advancing pregnancy. For the umbilical artery, aorta and cerebral
      artery, the earliest possible Doppler recordings and characteristics of the
      waveforms were established. The pulsatility index of the umbilical arteries and
      fetal aorta showed a sharp decrease towards the 16th week. The pulsatility index
      of the fetal cerebral artery showed only a mild decrease towards week 16. In a
      longitudinal analysis, there were significant changes of the resistance and
      pulsatility indices for each patient. In the vitelline artery, recordings were
      possible in eight out of 18 fetuses, and only in weeks 7 and 8 of gestation. The
      pulsatility index showed a wide range and was not dependent on menstrual
      age.Knowledge of the normal flow velocity waveforms in the maternal
      uteroplacental and fetal circulations early in pregnancy may lead to a better
      understanding of physiological mechanisms.

PMID- 12797163
TI  - Growth of the fetal gall bladder in normal pregnancies.
AB  - Our objective was to obtain dimensions of the fetal gall bladder as a basis, for
      further studies and to establish normative data to assess deviations in growth.
      The study group included 183 normal pregnant women from 13 to 40 weeks'
      gestation. Routine biometric measurements were obtained on all fetuses, including
      biparietal diameter, head and abdominal circumferences and measurements of the
      long bones and the two diameters of the fetal gull bladder. The gall bladder area
      and circumference were calculated for each gestational age.A linear growth
      function was observed across the gestational age and a first-degree correlation
      was found to exist between gestational age and both the longitudinal (r =
      0.77067; p < 0.00001; y = -0.41060 + 0.0907 x gestational age) and transverse (r
      = 0.602; p < 0.00001; y = 0.58567 + 0.01925 x gestational age) diameters of the
      fetal gall bladder. A significant correlation was also found between gull bladder
      area and gestational age (r = 0.6878; p < 0.00001), biparietal diameter (r =
      0.72768; p < 0.00001), abdominal circumference (r = 0.71363; p < 0.00001) and
      femoral length (r = 0.72190; p < 0.00001). In addition, a significant correlation
      was found between gall bladder circumference and gestational age (r = 0.76181; p
      < 0.00001), biparietal diameter (r = 0.80039; p < 0.00001), abdominal
      circumference (r = 0.78030; p < 0.00001) and femoral length (r = 0.79694; p <
      0.00001). These results provide normative data of the fetal gall bladder in
      various dimensions and across gestational age. In addition, the data offer the
      potential for prenatal diagnosis of additional lesions in the extrahepatic
      biliary duct system.

PMID- 12797164
TI  - The effect of an abnormal umbilical artery Doppler on the management of fetal
      growth restriction: a survey of maternal-fetal medicine specialists who perform
      fetal ultrasound.
AB  - The purpose of this survey was to determine if an abnormal Doppler ultrasound
      scan of the umbilical artery alters the management of patients with fetuses with
      varying degrees of asymmetrical growth restriction remote from term. A survey was
      conducted of Maternal-Fetal Medicine specialists who practiced in the United
      States. Three cases of increasing severity of asymmetrical growth restriction
      (abdominal circumference > 2 standard deviations below the mean) were presented,
      each with a normal or abnormal Doppler of the umbilical artery. The estimated
      fetal weights were between the 15th and 25th centiles (Case 1), 10th and 15th
      centiles (Case 2), and less than the 10th centile (Case 3). Each physician was
      asked to respond to questions regarding the frequency (none, 2 weeks, 3 weeks, 4
      weeks) of repeat ultrasound scans, the recommendation for maternal bed rest and
      its duration (none, 5 hours, 12 hours), and the choice of antepartum testing
      (none, nonstress test, non-stress test plus amniotic fluid index, contraction
      stress test, biophysical profile).A completed survey was returned by 199 of 900
      (22%) Maternal-Fetal Medicine specialists who practiced in 33 of 50 states. Of
      respondents, 95% performed fetal ultrasound. Over 98% of respondents repeated the
      ultrasound examination irrespective of the degree of growth restriction.
      Comparing the affect of a normal versus an abnormal Doppler for Case 1, there was
      a significant increase in the following: repeat ultrasound at the 2-week interval
      (46 vs. 68%, p < 0.00002); recommendation for maternal bed rest (55 vs. 80%, p <
      0.00002); the duration of bed rest for 12 h (17 vs. 46%, p < 0.000001);
      recommendation for antepartum testing (82 vs. 96%, p < 0.00002); utilization of
      the contraction stress test (1 vs. 7%, p < 0.004); and the biophysical profile
      (17 vs. 27%, p < 0.02). Comparing the effect of a normal versus an abnormal
      Doppler on management for Case 2, there was a significant increase in the
      following: recommendation for maternal bed rest (80 vs. 89%, p < 0.02); duration
      of bed rest for 12 h (34 vs. 63%, p < 0.000001); and the recommendation for
      antepartum testing (95 vs. 99%, p < 0.04). Comparing the effect of a normal
      versus an abnormal Doppler on management for Case 3, the only significant
      increase was the recommendation for 12 h of bed rest (72 vs. 84%, p < 0.006).
      Comparison of the trends in management as the cases became more severe (Case 1
      through Case 3) in the normal Doppler group demonstrated a significant increase
      in recommendation for repeat ultrasound at the 2-week interval (46 to 76%, p <
      0.000001); recommendation for bed rest (55 to 92%, p < 0.000001); the duration of
      bed rest for 12 h (17 to 72%, p < 0.00001); recommendation for antepartum testing
      (82 to 100%, p < 0.000001); use of the contraction stress test (1 to 10%, p <
      0.0004); and the biophysical profile (17 to 46%, p < 0.00009). Comparison of the
      trends in management as the cases became more severe (Case 1 through Case 3) in
      the abnormal Doppler group demonstrated a significant increase in recommendations
      for bed rest (80 to 96%, p < 0.000007); the duration of bed rest for 12 h (46 to
      84%, p < 0.000002); and use of the biophysical profile (27 to 55%, p < 0.000001).
      An abnormal Doppler ultrasound scan of the umbilical artery appears to alter the
      recommendations for management of fetuses with varying degrees of growth
      restriction.

PMID- 12797165
TI  - The characterization of flow signals from tubal and ovarian arteries using
      intraoperative continuous wave Doppler.
AB  - Ovarian vascular Doppler is a promising screening test for early ovarian cancer
      detection. However, disagreements on flow indices used, flow signal shapes and
      ovarian vessel localization cause continuing controversy. We aimed at clarifying
      some of this confusion by directly measuring the adnexal arterial blood flow
      during laparotomy. A 10-MHz continuous Doppler probe was used to examine adnexal
      vessels in 24 patients undergoing laparotomy for benign gynecological pathology.
      Resistance (RI) and pulsatility (PI) indices were calculated for each vessel and
      the shape of the flow signals was noted. The tubal arteries showed a low-velocity
      flow pattern with relatively high end-diastolic flow when compared to the ovarian
      artery signals obtained from the infundibulopelvic ligament.The mean RIs for the
      tubal artery and ovarian artery in the infundibulopelvic ligament were 0.59 +/-
      0.02 and 0.73 +/- 0.02, respectively. The mean PIs for the tubal and ovarian
      artery in the infundibulopelvic ligament were 1.11 +/- 0.09 and 1.53 +/- 0.1,
      respectively. The tubal artery showed a significantly lower RI and PI when
      compared to the ipsilateral ovarian artery at the infundibulopelvic ligament (p <
      0.001 and p = 0.002, respectively) and its hilar branches (p = 0.03 for RI and p
      = 0.03 for PI). We conclude that tubal artery flow signals, which are measured
      directly for the first time in this study, are characteristic and are distinct
      from the ovarian artery signals. Tubal artery signals might be erroneously picked
      up during transvaginal color Doppler sonography of the ovaries, especially in the
      presence of conditions causing a decreased impedance to blood flow in the pelvis,
      such as ovarian tumors. Recognizing the flow signal from the tubal artery may
      help in differentiating ovarian and tubal vessels detected during color Doppler
      sonography.

PMID- 12797166
TI  - Precocious signs of polycystic ovaries in obese girls.
AB  - As several studies have reported that 35% of patients with polycystic ovary
      syndrome are obese and that this syndrome seems to originate during the early
      phase of sexual maturation, we undertook a study of such subjects. We studied
      ultrasound and hormonal findings in 49 obese girls aged from 7.9 to 19.10 years,
      with a mean excess weight of 44%; 23 premenarcheal girls and 26 postmenarcheal
      girls with mean gynecological age of 2.5 years. As controls, we studied 18 girls
      in the pubertal phase and 17 healthy girls with regular menses, matched for age
      and gynecological age. Pelvic ultrasonography was carried out in all girls and
      estrone, estradiol, progesterone, prolactin, follicle stimulating hormone,
      luteinizing hormone, sex hormone binding globulin (SHBG), testosterone, free
      testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA
      S), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured by
      radioimmunoassay in 11 of the 18 postmenarcheal girls. Five girls (10.2%) with
      excess weight of > 40% presented with mild or severe hirsutism based on Ferriman
      and Gallway scores; six (12.2%) presented with acne and 14 (28.5%) presented with
      acanthosis nigricans.Hormonal evaluation showed elevated levels of estrone (p <
      0.005) and testosterone (p < 0.01) but lower than normal levels of SHBG (p <
      0.05) and estradiol (p <0.05). On the basis of our results, 23%) of the
      postmenarcheal obese subjects showed clinical, hormonal and ultrasonographic
      signs of polycystic ovaries, and 23% of postmenarcheal obese girls showed
      multifollicular ovaries. Six of these, at 1 year after menarche, showed a uterine
      cross-sectional area larger than normal for gynecological age (21.92 +/- 5.64
      cm(2) vs. 16.36 +/- 2.34 cm(2)). Further serial echographic studies and a careful
      follow-up will demonstrate if both multifollicular ovaries and increased uterine
      cross-sectional area in obese girls are precocious signs of polycystic ovaries.

PMID- 12797167
TI  - The use of transvaginal ultrasonography compared to routine gynecological
      examination to check the location of an intrauterine contraceptive device.
AB  - The objective of this study was to evaluate the use of transvaginal
      ultrasonography compared with a routine gynecological examination to check the
      location of an intrauterine contraceptive device (IUCD). Fifty-two women
      attending the antenatal cure unit at Lundby hospital for contraceptive guidance
      were included in the study. All women had an IUCD inserted at this visit and were
      examined bimanually and by speculum. The same examination was repeated and a
      transvaginal ultrasound scan was carried out at 1 week and then 3 months later.
      In 51 women, the threads of the device could be identified at the time of the
      gynecological examination and the IUCD was considered to be correctly positioned.
      In one woman, the threads could not be seen, but transvaginal ultrasonography
      confirmed that the position of the device was at the fundus of the uterus. Forty
      eight women were judged by ultrasound examination to have the device optimally
      placed in the uterine cavity. In four women, although the IUCD was apparently
      correctly located according to the gynecological examination, the device was
      shown by ultrasonography to be misplaced.We suggest that transvaginal
      ultrasonography should replace the conventional gynecological examination as the
      best method of checking the location of an IUCD.

PMID- 12797168
TI  - Endometrial thickness as measured by transvaginal sonography: interobserver
      variation.
AB  - Transvaginal sonography of the uterus has become an important tool for diagnosing
      endometrial pathology in women with postmenopausal bleeding. One parameter that
      has been claimed to be important for curly detection of endometrial pathology in
      this group of women is the endometrial thickness. The purpose of this study was
      to evaluate the reproducibility of measurements of endometrial thickness as
      performed by five inexperienced doctors and one doctor experienced in the
      transvaginal sonography technique. The endometrial thickness as measured by the
      experienced doctor was regarded as the 'true measurement', and the mean
      discrepancy from this true measurement was 1.5 mm for the inexperienced doctors.
      No endometrial pathology was found at the histopathological examination after
      dilatation and curettage (D & C) when the endometrial thickness was measured as
      <or= 4 mm by both the inexperienced and the experienced doctors. However, there
      were considerable differences between the results obtained by the five
      inexperienced doctors. If this method is to be used for identifying those women
      who will not have a D & C performed, based on the findings of a thin endometrium
      (<or= 4 mm), training is needed in order to minimize the error. We believe that
      this will make measurement more accurate and it may then be used to exclude
      endometrial abnormality in women with postmenopausal bleeding.

PMID- 12797169
TI  - Transvaginal sonography of the internal genital organs in postmenopausal women on
      low-dose estrogen treatment.
AB  - Thirty healthy postmenopausal women with symptoms and signs of atrophic vaginitis
      due to estrogen deficiency were examined with transvaginal ultrasound. The
      endometrial thickness, the uterus and the ovaries were measured before and after
      6 months of treatment with a low dose of estradiol released from a vaginal ring.
      The mean endometrial thickness, before and after the treatment, was 2.9 mm and
      2.5 mm, respectively. There were no changes in endometrial volume or uterine
      thickness and volume during the treatment period. The mean volume of the
      postmenopausal ovary before treatment was 4.2 ml, and there was no difference
      after treatment or between the right and the left side. With a low dose of
      estradiol, administered locally, all the women were relieved from their
      deficiency symptoms, without any effect on the endometrium, the uterus or the
      ovaries when measured by transvaginal ultrasound.

PMID- 12797170
TI  - Fetal liver hemangioma and chorioangioma: two unusual cases of severe fetal
      anemia detected by ultrasonography and its perinatal management.
AB  - Severe anemia was diagnosed by cordocentesis in two fetuses, one with a large
      chorioangioma, the other with a liver hemangioma. Despite the presence of a
      chronic fetotumoral shunt, both cases were partly treated by a fetal
      intravascular transfusion, followed by an elective Cesarean section. This
      'predelivery' management of anemia should improve neonatal morbidity associated
      with severe hematological and acid-base balance disorders.

PMID- 12797171
TI  - Prenatal diagnosis of placental chorioangioma: contribution of color Doppler
      ultrasound.
AB  - A case of placental chorioangioma was diagnosed at 35 weeks' gestation using
      color Doppler ultrasound. Color flow imaging showed an intraplacental hypoechoic
      mass fed directly by the anomalous chorionic tumor vessels arising from the
      insertion of the umbilical cord. Hypervascularization was present in some areas
      of the tumor. The diagnosis of typical 'angiomatous' type was confirmed by
      histopathological examination following delivery.

PMID- 12797172
TI  - Antenatal diagnosis and treatment of fetal hydrops secondary to pulmonary
      extralobar sequestration.
AB  - Bronchopulmonary sequestration with associated non-immune hydrops has been
      previously reported with generally poor prognosis for the neonate. The vast
      majority of sequestrations are discovered postnatally, and less than half are
      correctly identified as sequestration before birth.Until recently, treatment for
      pulmonary sequestration was limited to postnatal respiratory support and
      resection of the sequestered lung. But aggressive respiratory support does not
      succeed in salvaging infants with underlying pulmonary hypoplasia. In our report,
      we describe the antenatal treatment of pleural effusions complicated by hydrops
      fetalis secondary to a bronchopulmonary sequestration, successfully managed with
      a transthoracic catheter placement. This therapy resulted in the resolution of
      pleural effusion, polyhydramnios and hydrops, with a good fetal outcome.

PMID- 12797173
TI  - An approach to multifetal pregnancy reduction in a pregnancy of grand order (12
      fetuses).
AB  - Our objective was to determine the best method to approach a multifetal pregnancy
      reduction of a patient with a multiple pregnancy of grand order (12 fetuses).
      Transvaginal ultrasound-guided reduction was performed in three stages.
      Successful outcome was achieved. The patient delivered twins at 37 weeks'
      gestation. The published and unpublished literature is reviewed and discussed in
      the light of this case. Our conclusion is that a multifetal pregnancy reduction
      of grand order can be performed in stages to achieve the desired number of
      fetuses.

PMID- 12797174
TI  - Uteroplacental Doppler and aspirin therapy in the prediction and prevention of
      pregnancy complications.

PMID- 12797175
TI  - Should all pregnant women have an ultrasound examination?

PMID- 12797176
TI  - Sonography of fetal ventriculomegaly: the never-ending story.

PMID- 12797177
TI  - Ultrasound in urogynecology.

PMID- 12797178
TI  - Early development of the forebrain and midbrain: a longitudinal ultrasound study
      from 7 to 12 weeks of gestation.
AB  - The purpose of this longitudinal study was to describe embryonic development in
      vivo. Twenty-nine healthy pregnant women were examined five times with
      transvaginal ultrasound between 7 and 12 weeks of gestation. Brain structures
      such as the hemispheres, the choroid plexus of the lateral ventricles, the
      diencephalon, and the mesencephalon were identified and, if possible, measured.
      It was possible to identify the cavities of the hemispheres, the diencephalon and
      the mesencephalon during week 7. The choroid plexus of the lateral ventricles
      became visible during week 8. The growth of the length, width and height of the
      hemispheres and the choroid plexus of the lateral ventricles was curvilinear,
      that of the mesencephalon and diencephalon was linear except for the width of the
      diencephalon. The width of the diencephalon, the future third ventricle, was 1.1
      mm during week 7. It decreased to 0.8 mm at 12 weeks. Apart from the
      rhombencephalon, the cavity of the diencephalon was the large dominating brain
      structure during embryonic development. In early fetal life the cerebral
      hemispheres took over this dominance. The study was in full agreement with
      descriptions in the embryological literature, both concerning the anatomical
      features and their chronological formation.

PMID- 12797179
TI  - In utero detection of ventriculomegaly during the second and third trimesters by
      transvaginal sonography.
AB  - The purpose of this study was two-fold. The first was to extend the previously
      developed and published nomograms of the fetal lateral ventricles from 18 weeks
      back to 14 weeks of gestation using transvaginal sonography, and, second, to test
      the performance of the nomograms by plotting the measurements of 36 fetuses whose
      transabdominal and/or qualitative transvaginal scans were suspicious for
      ventriculomegaly. In all the cases in which postnatal confirmation of the
      diagnosis was possible, prenatal ultrasound correctly identified the lesion.
      Although a total of nine nomograms was created, the clinically meaningful
      measurements were: the height of the occipital horn on the parasagittal plane,
      and the two ratios derived from the measurements performed on the parasagittal
      plane. In conclusion, the transvaginally generated nomograms were useful for the
      correct identification of fetuses with ventriculomegaly.

PMID- 12797180
TI  - Life without amniocentesis: elevated maternal serum alpha-fetoprotein in the
      Manitoba program 1986-91.
AB  - Pregnant women demonstrating an elevated maternal serum alpha-fetoprotein level
      are at increased risk for fetal neural tube defect or other anomaly. Diagnostic
      procedures to evaluate these pregnancies include high-resolution ultrasound and
      amniocentesis to measure amniotic fluid levels of alpha-fetoprotein and N
      acetylcholinesterase. We wished to examine the efficacy of detailed ultrasound
      examination alone, in evaluation of women with 'unexplained' elevation of
      maternal serum alpha-fetoprotein. The results showed that no neural tube defects
      were missed in the assessment of 1325 pregnancies with a raised level of maternal
      serum alpha-fetoprotein over 6 years, despite complete reliance on ultrasound in
      98%. Detailed fetal ultrasound evaluation by experienced personnel is adequate to
      identify all cases of neural tube defects in a selected high-risk population.

PMID- 12797182
TI  - Fetal echocardiography: the identification of two of the pulmonary veins from the
      four-chamber view during the second trimester of pregnancy.
AB  - Identification of two of the pulmonary veins as they enter the left atrium is
      important to the diagnosis of the visceroatrial situs for fetuses with normal and
      abnormal echocardiographic findings. In this study, we investigated the ability
      to demonstrate these veins in 734 fetuses varying in gestational age from 13 to
      21 weeks. Transvaginal and transabdominal B-mode ultrasound and color flow
      Doppler were used for the examination. With the use of the transvaginal route,
      the highest visualization rate, 85-95%, was achieved in fetuses of 14-15 weeks of
      gestation. With the use of the transabdominal route, the highest visualization
      rate, 95-97%, was achieved in fetuses of 20-21 weeks of gestation. This
      examination enabled the correct diagnosis to be made of complex cardiac
      anomaly.Visualization of the pulmonary veins with B-mode ultrasound aided by
      color flow Doppler can be accomplished in the majority of fetuses, while the four
      chamber view is studied.

PMID- 12797181
TI  - Small hyperechoic ventricle: a benign foci of the fetal cardiac sonographic
      finding?
AB  - The objective of our study was to determine the significance of antenatally
      detected, small hyperechoic foci in the fetal cardiac ventricle. In a 13-month
      period, we identified 25 fetuses with such a finding, an incidence rate of 0.46%.
      The hyperechoic foci in 24/25 fetuses were seen during follow-up serial scans.
      The size ranged from 1 to 6 mm. All had a normal fetal echocardiogram at 20-22
      weeks' gestation. Eleven of the 24 neonates had a normal postnatal echocardiogram
      in the first 4 weeks of birth. One neonate had a previously undiagnosed
      transposition of the great vessels and no residual hyperechoic focus. Twelve had
      an echogenic focus located at the level of the chordae tendineae and papillary
      muscles in the left ventricle. In each of these 12 neonates, there was normal
      ventricular function determined by measuring the shortening fraction, and a
      competent atrioventricular valve. When hyperechoic foci are identified, baseline
      antenatal echocardiography should be performed to confirm their benignity. With
      an otherwise normal fetal and clinical neonatal evaluation, serial antenatal and
      confirmatory postnatal echocardiography are unnecessary. A possible relationship
      to other cardiac anomalies or aneuploidies requires further study.

PMID- 12797183
TI  - Real-time quasi-three-dimensional viewing in sonography, with conventional, gray
      scale volume imaging.
AB  - Real-time three-dimensional views of the fetus can be obtained with minor
      modification to conventional scanners. The modification consists of placing a
      divergent lens in the out-of-scan plane of the transducer to generate a beam fan
      beam in the insonated volume. All of the echoes from which insonates a volume
      rather than a slice of tissue. Scanning is performed using oblique angles of
      incidence to provide total reflection conditions. Echoes are then received only
      from anterior surfaces, automatically generating the three-dimensional views.
      Intriguing portrayal of fetal detail can be obtained with this form of imaging
      which is likely to expand the clinical utility of sonographic examinations.

PMID- 12797184
TI  - Does measurement of amniotic fluid index detect changes in amniotic fluid volume
      after second-trimester amniocentesis?
AB  - The objective of this study was to establish whether variations of amniotic fluid
      volume induced by second-trimester amniocentesis could be detected by serial
      measurements of amniotic fluid index. A total of 130 singleton pregnancies
      undergoing second-trimester amniocentesis for genetic indications were
      considered. Amniotic fluid index was measured at three different time intervals:
      30-60 min before amniocentesis, immediately after the procedure, and 60 min after
      the procedure. Serial measurements were obtained either by a single operator (n =
      55) or by the three independent operators (n = 75). Significantly lower amniotic
      fluid index values were demonstrated immediately after amniocentesis when
      compared with the pre-amniocentesis and subsequent measurements in the study
      design with both the single and multiple operators. No statistically significant
      changes were found between the first amniotic fluid index measurements and those
      obtained 1 h after amniocentesis. These results suggest that second-trimester
      amniocentesis induces a temporary decrease of amniotic fluid volume detectable by
      serial amniotic fluid index measurements, no longer evident 1 h after the
      procedure.

PMID- 12797185
TI  - A novel technique for measuring bladder wall thickness in women using
      transvaginal ultrasound.
AB  - A new technique of measuring bladder wall thickness using transvaginal ultrasound
      is described. Measurement of the bladder wall using ultrasound was found to have
      a good intra- and interobserver reproducibility. Measurements of the bladder wall
      thickness were altered if more than 50 ml of fluid was within the bladder. Forty
      five women with urinary symptoms were recruited from the urodynamic clinic; those
      with urodynamically diagnosed detrusor instability were found to have
      significantly thicker bladder walls than women with urodynamically diagnosed
      genuine stress incontinence. Application of this technique may be useful in the
      diagnosis of detrusor instability.

PMID- 12797186
TI  - Postmenopausal intrauterine fluid collection: correlation between ultrasound and
      hysteroscopy.
AB  - Postmenopausal intrauterine fluid is an alarming sign related to malignancy.
      Twenty postmenopausal women with intrauterine fluid were prospectively studied by
      means of sonographic evaluation, and hysteroscopic and histological examinations,
      to determine the correlation between ultrasound and hysteroscopy. All patients
      underwent endovaginal sonography, followed by hysteroscopy. Biopsies were
      performed on all patients with abnormal endometrium, and randomly on selected
      patients with normal or atrophic endometrium. In patients with abnormal
      endometrial structure and thickness (< 4 mm), two cases of endometrial cancer
      were histologically detected and one was revealed by cytology (Pup smear).
      Seventeen patients with thin endometrium (<or= 4 mm) had no pathology.
      Sonographic, hysteroscopic and histological findings correlated well in all
      cases.

PMID- 12797187
TI  - Sonohysterography for distinguishing endometrial thickening from endometrial
      polyps in postmenopausal bleeding.
AB  - Sonohysterography, or sonographic uterine cavity visualization by uterine cavity
      distension, may help to distinguish true endometrial thickening from other
      intracavitary pathological conditions, assuming the same sonographic appearance.
      We examined 1.5 women with a thickened endometrium (range 10-25 mm) in sonography
      performed for postmenopausal bleeding. Sonohysterography revealed a polypoid
      structure in seven women, a normal uterine cavity in four women, and a thickened
      endometrium in four women. All the women underwent hysteroscopic evaluation of
      the uterine cavity. Hysteroscopy confirmed the sonohysterographic findings in 14
      women (93.3%). Hysteroscopic resection of the polypoid structure was performed
      while the other patients underwent diagnostic curettage. Histological examination
      of the seven polypoid structures revealed benign endometrial polyps in six
      patients, and one pedunculated submucous fibroid. In the patients undergoing
      diagnostic curettage, histological examination revealed three cases of glandular
      hyperplasia, one of cystic (atrophic) hyperplasia, and one of papillary
      endometrial adenocarcinoma. Two cases were inadequate for diagnosis. The
      advantage of sonohysterography in distinguishing endometrial thickening from
      intracavitary polyps or fibroids was clearly demonstrated. This technique can
      help in tailoring the correct treatment in various conditions presenting as
      postmenopausal bleeding.

PMID- 12797188
TI  - Doppler study of the uterine artery in patients using an intrauterine
      contraceptive device.
AB  - A Doppler flow study of the uterine artery was performed using transvaginal
      sonography in 68 women, including 44 using an intrauterine contraceptive device
      (IUCD) and 24 control women who were not using any method of contraception. Both
      the pulsatility index (PI) and resistance index (RI) were significantly lower in
      women with IUCD-induced bleeding than in those without abnormal vaginal bleeding
      (p < 0.001) or in women not using any method of contraception (p < 0.001). No
      significant variations in PI and RI levels (p > 0.05) were found with the
      duration of IUCD application or the duration of IUCD-induced bleeding in patients
      using the device. Also, no significant changes in blood flow indices were
      demonstrated between women using the device without abnormal vaginal bleeding and
      the control group. These preliminary results suggest that some women are more
      prone to develop IUCD-induced bleeding than others, and this bleeding may be due
      to decreased vascular resistance in the uterine artery. Transvaginal Doppler
      study of the uterine artery may be a helpful technique to identify such women.

PMID- 12797189
TI  - Arteriovenous malformation of the uterus associated with a missed abortion.
AB  - Arteriovenous malformation of the uterus is a rare uterine abnormality. This
      entity is generally associated with the presence of molar disease,
      choriocarcinoma and uterine surgery, but may be congenitally acquired. The
      presence of an arteriovenous malformation generally leads to unexplained profuse
      uterine bleeding. The diagnosis of this entity has traditionally been made by
      arteriography, and the treatment is usually hysterectomy. We present a patient
      with an arteriovenous malformation of the uterus whose prior delivery was by
      Cesarean section. The patient experienced episodes of heavy vaginal bleeding in
      the first month following the procedure of suction curettage for a first
      trimester pregnancy loss. Chorionic villus sampling performed prior to the
      procedure showed a chromosomally normal fetus. The diagnosis of an arteriovenous
      malformation was made by color Doppler velocimetry and confirmed with
      arteriography. The patient desired to maintain her fertility. Interventional
      radiological techniques were successfully utilized to obliterate the
      arteriovenous malformation with the use of polyvinyl alcohol particles (250 micro
      m) and gelfoam. Discussion includes the presenting signs and symptoms along with
      the method of both diagnosis and conservative management.

PMID- 12797190
TI  - Expectant management of interstitial pregnancy.
AB  - A case of interstitial pregnancy is described. Transvaginal ultrasound
      examination, performed at 8 weeks' gestation, revealed an empty endometrial
      cavity with an eccentric gestational sac in the left uterine corner, with a clear
      separation between the uterine cavity (endometrium) and the gestational sac.
      Expectant management, consisting of repeated sonographic examinations and
      assessment of serum beta-human chorionic gonadotropin, resulted in a favorable
      outcome.

PMID- 12797191
TI  - Epignathus: clinical and sonographic observations of two cases.
AB  - The epignathus or mature pluritissued teratoma of the mid-line of the palate is a
      benign tumor for which the neonatal prognosis is related to the obstruction of
      the superior airway. This paper concerns observations of two cases, which
      developed in different ways. Echography enables diagnosis of this type of
      malformation which classically combines a heterogeneous polylobed mass,
      polyhydramnios and the absence of other morphological anomalies. It enables an
      accurate differential diagnosis to be made by eliminating the other masses of the
      cephalic region. Echographic diagnosis also allows a rational management decision
      to be made, i. e. termination of pregnancy if prognosis is poor, or continuation
      with multidisciplinary (neonatologist, obstetrician, surgeon) intervention at
      birth.

PMID- 12797192
TI  - Hysterosalpingo contrast sonography (HyCoSy) and its future role within the
      investigation of infertility in Europe.
AB  - An important part of any protocol for investigation of the infertile couple is
      the assessment of Fallopian tube patency in the woman, as this can influence the
      future course of treatment. X-ray hysterosalpingography and laparoscopy and dye
      tubation are currently the main procedures for investigating tubal patency, but
      the recent development of hysterosalpingo contrast sonography (HyCoSy) may offer
      some benefits over these two methods. HyCoSy involves a transvaginal ultrasound
      investigation of the Fallopian tubes both before and after the injection of an
      echo-enhancing agent into the tubes via the uterine cavity. Evidence of tubal
      flow with B-mode scanning is indicative of tubal patency. Clinical data using the
      echo-enhancing agent, Echovist, in over 600 patients, in addition to technical
      aspects of the HyCoSy procedures are reviewed. The data presented indicate that
      the sensitivity and specificity of HyCoSy compare favorably with the current
      'gold standard' techniques. HyCoSy is a safe, well-tolerated and relatively
      inexpensive procedure, which can be carried out in a short time during an
      outpatient consultation. Combining these undoubted benefits with the clinical
      results obtained to date would indicate that HyCoSy has the potential to be
      employed as a reliable and well-accepted procedure for assessing tubal patency as
      part of the investigation of infertility.

PMID- 12797195
TI  - Presentation of the Ian Donald Gold Medal to Manfred Hansmann.

PMID- 12797193
TI  - Fetal upper respiratory tract function in antenatally diagnosed congenital
      diaphragmatic hernia.

PMID- 12797196
TI  - Presentation of the Ian Donald Medal for technical development to Martin H.
      Wilcox.

PMID- 12797197
TI  - The ultrasound examination: content and cost containment.

PMID- 12797198
TI  - Is oligohydramnios a risk factor for infection in term premature rupture of
      membranes?

PMID- 12797199
TI  - Ovarian endoscopy: a new area for research.

PMID- 12797200
TI  - Is oligohydramnios a risk factor for infection in term premature rupture of
      membranes?
AB  - Our objective was to determine if a reduced volume of amniotic fluid is a risk
      factor for microbial invasion of the amniotic cavity in women with rupture of
      membranes at term. Transabdominal amniocentesis under ultrasound guidance was
      used to evaluate the microbiological state of the amniotic cavity in 53 patients
      with term premature rupture of membranes before vaginal examination. Amniotic
      fluid index was measured prior to the procedure in all cases. The prevalence of
      microbial invasion of the amniotic cavity was 32.1% (17/53). Women with microbial
      invasion of the amniotic cavity had a significantly lower median amniotic fluid
      index than did women without evidence of infection (median 4.4 cm, range 1.0-8.1
      vs. median 7.8 cm, range 1.3-14.4, respectively; p < 0.001). An amniotic fluid
      index of < 5 cm had a sensitivity of 71% (12/17) a specificity of 89% (32/36), a
      positive predictive value of 75% (12/16) and a negative predictive value of 87%
      (32/37) in the prediction of microbial invasion of the amniotic cavity. Among
      women who delivered vaginally, those with an amniotic fluid index of < 5 cm had a
      higher rate of endometritis than those with an amniotic fluid index of >or= 5 cm
      (19% (3/16) vs. 0% (0/26), respectively; p < 0.05). We conclude that women with
      term premature rupture of membranes and an amniotic fluid index of < 5 cm are at
      an increased risk for microbial invasion of the amniotic cavity and puerperal
      infection after a vaginal delivery.

PMID- 12797201
TI  - Routine ultrasonography in utero and speech development.
AB  - The purpose of this paper is to examine a possible association between prenatal
      ultrasonography and delayed speech among children. A follow-up study was carried
      out on primary school children born to women who took part in two randomized
      controlled trials of routine ultrasonography during pregnancy. Of 2428 eligible
      singletons, 2161 (89%) were followed up with a parental questionnaire and with
      information from maternal and child health centers. Parents assessed the
      development of speech during the childhood years and reported their observations
      in a questionnaire. Maternal and child health center records provided data on the
      children's development of speech and any referrals of children to a speech
      therapist. No significant differences between ultrasound-screened children and
      their controls were found in the parental assessment of speech development.
      According to health center records, screened children were less likely to be
      referred to a speech therapist (odds ratio, 0.51; 95% confidence interval 0.31,
      0.85), but there were no other significant differences in speech development as
      reported in the health center records. We conclude that routine ultrasonography
      in utero is not associated with delayed speech in children.

PMID- 12797202
TI  - Transverse cerebellar diameter in small-for-gestational-age fetuses: pregnancy
      dating is possible only when growth retardation is secondary to uteroplacental
      insufficiency.
AB  - The objective of this study was to establish whether measurement of the
      transverse cerebellar diameter to determine gestational age differs in small-for
      gestational-age fetuses with normal or abnormal Doppler velocity waveforms. Our
      secondary objective was to compare the efficacy of measurement of transverse
      cerebellar diameter with that of femur length in pregnancy dating among small-for
      gestational-age fetuses. A total of 107 small-for-gestational-age fetuses with
      established dates and free from structural and chromosomal abnormalities were
      considered for this study. According to the Doppler results, fetuses were divided
      into two groups: group A (n = 64), with normal Doppler values as expressed by a
      ratio of pulsatility indices between the umbilical artery and middle cerebral
      artery of <or= 95th centile of our reference limits for gestation; and group B (n
      = 43), with ratio of > 95th centile. Measurements of transverse cerebellar
      diameter and femur length were compared to previously established 95th centile
      prediction intervals. In both groups of small-for-gestational-age fetuses, the
      values for transverse cerebellar diameter were lower than in normally grown
      fetuses after normalization for gestational age. The difference was more evident
      in group A (p <or= 0.001) than in group B (p <or= 0.05). Only 68.7% of transverse
      cerebellar diameter values of group A fetuses fell within the normal limits for
      gestation, while this occurred in 90.6% of group B fetuses. When compared to the
      femur length, the transverse cerebellar diameter measurement appeared to be
      better for predicting gestational age in both groups of small-for-gestational-age
      fetuses (p <or= 0.001). However, this measurement may be used to estimate
      gestational age only in small-for-gestational-age fetuses with abnormal Doppler
      findings.

PMID- 12797203
TI  - Ductus venosus blood velocity and the umbilical circulation in the seriously
      growth-retarded fetus.
AB  - Based on the assumption that the ductus venosus is regulator of oxygenated blood
      in the fetus, the present study investigated the blood flow velocity of the
      ductus venosus in relation to the umbilical circulation in the that seriously
      growth-retarded fetus. The study group of 38 fetuses (gestational week 17-39) had
      no chromosomal aberrations or structural malformations and had an
      ultrasonographic biometry of < 2.5th centile and birth weight of <or= 2.5th
      centile. Of the 38 fetuses seven died in utero and four died postnatally. The
      ultrasonographic examination included pulsed Doppler measurement of the umbilical
      artery pulsatility index (PI), the umbilical vein dimension and blood flow
      velocity, and the peak and maximum blood flow velocities of the ductus venosus.
      The majority of fetuses had a raised PI in the umbilical artery (26/38) and
      reduced blood flow in the umbilical vein (25/33). Despite such changes in the
      umbilical circulation, a normal peak velocity in the ductus venosus was
      maintained in all fetuses. During the atrial contraction, however, 13 fetuses had
      reduced or reversed blood velocity in the ductus venosus. Reduced ductus venosus
      velocity during atrial contraction seemed to be a serious finding linked to
      raised PI and absent or reversed end-diastolic flow in the umbilical artery, and
      umbilical vein pulsation. The results support the assumption that the blood flow
      of the ductus venosus is a preferential bloodstream in the human fetus that is
      maintained within normal ranges as long as possible during placental hemodynamic
      compromise.

PMID- 12797204
TI  - Color Doppler identification of a pericardial effusion in the fetus.
AB  - The aim of the study was to determine whether color Doppler identifies abnormal
      fluid within the pericardial space of the fetal were referred for heart. Second-
      and third-trimester fetuses diagnostic ultrasound. The four-chamber view of the
      fetal heart was imaged with real-time ultrasonography and examined for the
      presence or absence of separation of the pericardium from the epicardium, which
      extended from the atrioventricular junction toward the apex of the ventricle. To
      examine the pericardial space, the color Doppler maximal velocity was set at low
      Nyquist limits (0.08-0.24 m/s). In each fetus the transducer was angled so that
      the axis of the interventricular septum was parallel or tangential to the
      ultrasound beam to optimize the color Doppler recording. The control group
      consisted of 50 fetuses (16-38 weeks of gestation) who did not demonstrate
      evidence of pericardial effusion when examined with real-time ultrasound. Second-
      and third-trimester fetuses were selected from our database who demonstrated a
      pericardial effusion identified with real-time ultrasound. Color Doppler signals
      were not identified within the pericardial space in the 50 control fetuses.
      Fetuses with a pericardial effusion identified with real-time ultrasound
      demonstrated color Doppler within the pericardial space which was opposite to the
      direction of blood entering and exiting the ventricles. Color Doppler enhanced
      the detection of a pericardial effusion in the second-trimester fetus when the
      axis of the heart was and third-parallel or tangential to the ultrasound beam,
      which is suboptimal for real-time imaging. Color Doppler provides a new method to
      identify a pericardial effusion in the fetus during the second and third
      trimesters of pregnancy and complements the real-time examination.

PMID- 12797205
TI  - Doppler flow velocity waveforms in the fetal ductus arteriosus during the first
      half of pregnancy: a reproducibility study.
AB  - Reproducibility of flow velocity waveform measurement in the fetal ductus
      arteriosus was studied in 52 normal pregnancies between 11 and 25 weeks of
      gestation. The flow velocity parameters studied were the peak systolic velocity,
      mean velocity, end-diastolic velocity, flow velocity integral and acceleration
      time. In each woman two consecutive measurements were performed with a time delay
      of 15 min. An acceptable reproducibility was achieved for all flow velocity
      parameters, except for the acceleration time and end-diastolic velocity.

PMID- 12797206
TI  - Transvaginal ultrasound-guided ovarian endoscopy: a novel approach to the
      assessment of ovarian tumors.
AB  - The investigation of ovulatory dysfunction and the characterization of ovarian
      cystic tumors remain two major problems in gynecology. One of our limitations is
      the resolution of imaging techniques currently available. We describe the use of
      a fiberoptic endoscope to inspect the internal appearance of five different
      ovarian cystic lesions under the guidance of transvaginal ultrasound. The images
      obtained allow the operator to visualize structures of less than 1.0 mm in
      diameter, and so introduce the possibility of identifying both the cumulus
      oophorus in younger women, and very small papillary projections within
      potentially malignant ovarian cysts.

PMID- 12797207
TI  - Transvaginal sonography in the diagnosis of pelvic malignant recurrence:
      integration of sonography and needle-guided biopsy.
AB  - The aim of this study was to evaluate the efficiency of transvaginal sonography
      and sonography plus needle biopsy in detecting pelvic malignant recurrence. We
      scanned 24 patients already treated for gynecological malignancy, 21 of whom
      underwent needle biopsy under sonographic guidance. Thirteen patients were
      affected by cervical cancer, ten by ovarian cancer, and one by endometrial
      ovarian carcinoma. Sonography detected 16 solid or cystic-solid masses (median
      size 52 mm, range 15-85 mm), one case of ascites, and one liquid mass (hematoma).
      All the patients in whom a suspicious mass was detected had recurrence. In the
      six patients in whom no mass was visible, two had recurrence. Needle biopsy was
      able to demonstrate recurrence in 17 patients (also in two false-negative scans).
      In one, even though sonography detected a mass, the histological sample was
      negative, but recurrence was later diagnosed by laparotomy.Accuracy, sensitivity
      and specificity of transvaginal sonography were respectively 91.6%, 89.4% and
      100%. The positive predictive value was 100% and the negative predictive value
      was 71.4%. Transvaginal sonography was shown to be a useful means of detecting
      pelvic recurrence.

PMID- 12797208
TI  - Fetal cardiac and extracardiac flows preceding intrauterine death.
AB  - Extracardiac and cardiac flow velocity waveforms were recorded in a severely
      growth-retarded fetus 1 day and a few hours before fetal death. At the first
      scan, the typical Doppler patterns of a growth-retarded fetus were found, but the
      brain-sparing effect was lost at the last examination and a huge tricuspid
      insufficiency was demonstrated.

PMID- 12797209
TI  - The value of color Doppler ultrasound in the prenatal diagnosis of hypoplastic
      umbilical artery.
AB  - The prenatal diagnosis of hypoplastic umbilical artery has recently been
      reported, based on the visualization of discordant size between both umbilical
      arteries in association with discordant umbilical artery flow velocity waveforms.
      In this report we present two cases of hypoplastic umbilical artery and describe
      the use of color flow imaging and Doppler ultrasound in the prenatal evaluation
      of this condition. The principal advantages of these techniques include the
      confirmation of blood flow within the hypoplastic artery, thus ruling out the
      possibility of an atrophic non-functional artery, and the demonstration of size
      discrepancy at the level of the intra-abdominal portion of the umbilical
      arteries, validating the intra-amniotic cord findings. Color Doppler ultrasound
      is an important tool for diagnosing and evaluating vascular anomalies affecting
      the umbilical cord.

PMID- 12797210
TI  - Prenatal diagnosis of umbilical cord pseudocyst.
AB  - The association between umbilical cord anomalies and chromosomal abnormalities
      has received little attention in the literature. In this report, we present two
      cases of umbilical cord pseudocyst incidentally detected by ultrasound prior to
      genetic amniocentesis performed for the indication of advanced maternal age. In
      the first case it was only the initial abnormal finding in a 21-week fetus
      ultimately found to have a trisomy 18. In the second case, detected at 26 weeks,
      the karyotype was normal and a healthy normal neonate was delivered at term. The
      finding of a umbilical cord cystic mass during prenatal sonographic examination
      should alert the clinician to the increased risk of aneuploidy.

PMID- 12797211
TI  - Ultrasonic antepartum assessment of a classical Cesarean uterine scar and
      diagnosis of dehiscence.
AB  - Prior classic incision through the uterine corpus carries the most significant
      risk of catastrophic uterine rupture and subsequent maternal and fetal morbidity
      or mortality. A trial of labor is not carried out in this group of patients, but
      the risk of uterine rupture exists during the antepartum period. An accurate and
      prospective method for diagnosing the presence of uterine defects or documenting
      their absence would be clinically useful. Our unusual case emphasizes the obvious
      need for antepartum sonographic scans of the classic uterine scar, starting from
      the third trimester to term, using the high-frequency (> 5 MHz) transducer.

PMID- 12797212
TI  - Prenatal ultrasound diagnosis of fetal candida infection: a complication of a
      retained intrauterine contraceptive device.
AB  - A 32-year-old woman was referred complaining of abdominal pain and bleeding at 18
      weeks' gestation. The striking finding on ultrasound examination was of
      symmetrically enlarged echogenic fetal lungs. In addition, mediastinal
      compression, increased echogenicity of the kidneys and bowel, an enlarged liver
      of decreased echogenicity, and hydrops fetalis, as evidenced by ascites and skin
      edema, were all present. The differential diagnosis included upper respiratory
      tract obstruction and cystic kidney disease. The presence of fetal hydrops
      together with the other findings suggested a poor outcome, and on these grounds
      therapeutic abortion was recommended and performed. Subsequent postmortem
      findings explained all the ultrasound abnormalities on the basis of extensive
      fetal candida infection. The presence of a retained intrauterine contraceptive
      device was considered to be the likely cause and the implications of this,
      together with the ultrasound abnormalities and differential diagnoses, are
      discussed.

PMID- 12797213
TI  - Doppler studies of fetal cerebral blood flow.
AB  - Doppler flow velocity waveforms from fetal cerebral vessels can be reliably
      obtained by a transabdominal or transvaginal scanning route. Changes in
      pulsatility imply alterations in cerebral impedance and reflect the physiological
      regulatory mechanisms underlying pathological processes during pregnancy. In
      fetuses severely distressed due to failure of placental function, the ratios
      reflecting the redistribution of fetal circulation (e.g. the 'brain-sparing
      effect') help to identify fetuses at risk for fetal hypoxia. Apart from providing
      an increase in medical knowledge, this non-invasive technique is proving to be
      clinically useful.

PMID- 12797214
TI  - Transcervical chorionic villus sampling in a bicornuate uterus.

PMID- 12797215
TI  - Third world congress of ISUOG: meeting report.

PMID- 12797217
TI  - Teaching ultrasonography in the field of obstetrics and gynecology.

PMID- 12797218
TI  - Prevalence and significance of polycystic ovaries.

PMID- 12797219
TI  - Tamoxifen and the uterus.

PMID- 12797220
TI  - Magnetic resonance imaging in pregnancy: study of fetal cerebral malformations.
AB  - This paper reports 15 examinations by magnetic resonance imaging (MRI) performed
      in pregnant women whose fetuses had cerebral malformations identified by
      sonography. In all the cases the fetuses were immobilized by ultrasound-guided
      intravenous or intramuscular curarization. The diagnoses by MRI and ultrasound
      differed only in one case where an occipital meningocele had first been
      suggested. No cerebral abnormalities were demonstrated in this case by the MRI
      study, and this was confirmed at birth. In the remaining 14 cases, MRI confirmed
      the ultrasound diagnosis of cerebral malformation. In four of these cases, MRI
      added some additional information to the ultrasound diagnosis of ventriculomegaly
      by detecting agenesis of the corpus callosum in two fetuses, one Chiari
      malformation and one triventricular hydrocephalus. Another two ultrasound
      diagnoses of microcephaly actually proved to be semilobar holoprosencephaly with
      MRI. In the following cases, the MRI diagnoses concurred with those of
      ultrasound, and was therefore used unnecessarily despite providing further
      anatomical details of the lesions: two cases of agenesis of the corpus callosum,
      one case of anencephaly, a cystic hygroma of the neck, an alobar
      holoprosencephaly, a Dandy-Walker malformation and a mild isolated hydrocephalus
      associated with diaphragmatic hernia. In one case of iniencephaly, sonography
      offered closer approximation to the correct diagnosis. The results obtained
      unequivocally confirm the high sensitivity of ultrasound examinations in the
      prenatal screening of cerebral malformations and show that MRI proves to be
      complementary in uncertain cases or when more accurate anatomical detail is
      required.

PMID- 12797221
TI  - Sonographic visualization of the fetal upper airway.
AB  - Laryngeal obstruction is a life-threatening condition which can sometimes be
      diagnosed by prenatal ultrasound examination. Dilatation of the fetal trachea is
      an important finding in these cases. Sonographic studies to evaluate the fetal
      upper airway were performed in 120 consecutive patients. The diameters of the
      trachea and pharynx were measured and our ability to visualize the trachea and
      the larynx was evaluated. The diameter of the trachea increased from a mean of
      2.4 mm at 18 weeks to 4.6 mm at 38 weeks. The mean diameter of the pharynx
      increased from 4.4 mm at 18 weeks to 8.8 mm at 38 weeks. The fetal larynx was
      adequately visualized in 67%) of the cases, while the entire trachea was seen in
      47% of the cases. Our success in visualizing the larynx and trachea was best
      between 20 and 30 weeks' gestation. This study shows that it is possible to
      obtain excellent views of the fetal airway in a high percentage of cases and
      reports the range of normal values for tracheal diameter. Early visualization of
      a diluted trachea may allow better management of a fetus with laryngeal
      obstruction.

PMID- 12797222
TI  - Incorporating the four-chamber view of the fetal heart into the second-trimester
      routine fetal examination.
AB  - The four-chamber view of the fetal heart is reported to he the most useful view
      for detecting congenital heart defects. In 7322 non-selected, consecutive
      pregnancies of women attending a second-trimester (18 weeks) routine ultrasound
      scanning program, we examined our ability to obtain a four-chamber view in the
      fetus within the 30 min generally allocated to do the scan and record data. Five
      trained nurse-midwives performed the examinations between June 1988 and September
      1990. In the first part of the study, a four-chamber view could not be obtained
      in 7%, while in the second part, the failure rate was 4%, which showed a learning
      effect over time. The demonstration of a four-chamber view was significantly
      better with a 5 MHz than with a 3.5 MHz transducer. The ability to obtain the
      four-chamber view improved as the gestational age increased. The main reason for
      not being able to obtain the four-chamber view with the 3.5 MHz transducer was
      poor imaging; for the 5 MHz transducer, it was an unfavorable position of the
      fetus. Education and experience, as well as good equipment, are important factors
      in obtaining good results. The time spent learning to obtain a four-chamber view
      reliably was relatively long.

PMID- 12797223
TI  - Measurements of fetal limb bones in early pregnancy.
AB  - The fetal humerus, radius/ulna, femur, tibia/fibula and foot were measured in 296
      pregnant women at 64-108 days' menstrual age, using vaginal sonography. All limb
      measurements correlated significantly with gestational age and biparietal
      diameter independently. Ratios of limb segment lengths did not change with
      gestation. Reference ranges (mean and 95% data intervals) were constructed for
      each limb segment. These data may prove useful in prenatal diagnosis of skeletal
      dysplasias and in the antenatal assessment of patients at risk of chromosomal
      abnormalities.

PMID- 12797224
TI  - Fetal biometry at 14-40 weeks' gestation.
AB  - Normal ranges for a wide variety of biometrical parameters were established from
      cross-sectional data on 1040 normal singleton pregnancies resulting in livebirth
      at term of normal, and appropriately grown infants. Patients were selected so
      that the birth weight distribution was similar to that reported by Yudkin and
      colleagues' and the ranges can, therefore, be used for any population that has a
      similar birth weight distribution.

PMID- 12797225
TI  - Presence of pulsations and reproducibility of waveform recording in the umbilical
      and left portal vein in normal pregnancies.
AB  - Reproducibility and inter-observer variability of intra- and extra-abdominal
      umbilical venous flow velocity and left portal venous flow velocity as well as
      heart-synchronous waveform pulsations in these vessels were studied in 23 women
      at 34-38 weeks of normal pregnancy.Limited reproducibility, expressed by large
      intra-patient coefficients and limits of agreement between two observers, was
      established for all standardized recording sites. Pulsations, defined as negative
      venous deflections of at least 10% of the mean velocity, were demonstrated at all
      locations ranging from 19.6% of the measurements at the free-floating loop of the
      umbilical vein to 78.4% of the measurements at the left portal vein. The present
      study shows that the limited reproducibility of venous flow velocity waveforms
      should be taken into consideration, and that the presence of pulsations can be
      demonstrated in normal late pregnancy.

PMID- 12797226
TI  - Transabdominal versus transvaginal ultrasound in the diagnosis of polycystic
      ovaries in a population of randomly selected women.
AB  - A study was conducted which compared transvaginal and transabdominal ultrasound
      in determining the prevalence of polycystic ovaries in a population of women.
      Women, chosen randomly from electoral rolls, were sent a letter inviting them to
      take part in a study determining the presence of polycystic ovaries. A
      transvaginal and transabdominal ultrasound scan was performed on day 5-9 of their
      menstrual cycles. A total of 187 women (mean age 33 years) took part in the
      study. The prevalence of polycystic ovaries was 21% (40/187) by transabdominal
      ultrasound and 27% (36/134) by transvaginal ultrasound. No differences existed
      between women with polycystic and normal ovaries with respect to uterine size and
      endometrial thickness. Mean ovarian volume was larger in women with polycystic
      ovaries irrespective of the use of hormonal contraception or breast feeding.
      There was no difference in the prevalence of polycystic ovaries diagnosed by
      transabdominal or transvaginal ultrasound in the group of randomly selected
      women. However, almost 20% of the women declined a transvaginal ultrasound
      examination.

PMID- 12797227
TI  - Ultrasound in the follow-up of young patients with malignant ovarian tumors after
      conservative surgery.
AB  - Ultrasound examinations were performed us a step in the follow-up of 62 patients
      previously treated with conservative surgery for malignant ovarian tumors. With a
      minimal follow-up period of 36 months (range 36-129) 12 recurrences of disease
      were observed in nine patients. When compared to other routine follow-up
      procedures, ultrasound examination proved to be the most effective procedure in
      the monitoring of these patients, correctly detecting ten recurrences. Physical
      and gynecological examinations detected seven, tumor marker measurements detected
      six and chest X-rays detected one. Ultrasound examination was 83% sensitive, 99%
      specific and 99% accurate in the detection of recurrent disease. In four
      recurrences leading to death, the diameters of the tumors at first detection were
      25, 50, 50 and 100 mm, significantly higher (p = 0.03) than in seven recurrences
      followed by complete response of the tumor (range 15-35 mm, median 30 mm).
      Ultrasound appears to be superior to physical and gynecological examination in
      early detection of recurrence; considering that smaller burdens of tumor at the
      time of recurrence seem to imply a better prognosis, ultrasound should be
      considered us a useful additional procedure in the follow-up of these patients.

PMID- 12797228
TI  - Intraventricular fused fornices: a specific sign of fetal lobar
      holoprosencephaly.
AB  - Lobar holoprosencephaly can be recognized in utero with sonography. However, a
      specific diagnosis is difficult and thus far has relied upon a qualitative
      evaluation of the morphology of the cerebral ventricles. In infants with this
      condition, magnetic resonance imaging demonstrates at times an abnormal
      appearance of the fornices, which are rudimentary and fused in to a single
      fascicle running within the third ventricle. In a 30-weeks' fetus affected by
      lobar holoprosencephaly, this finding could be well demonstrated by sonography
      and was confirmed after birth by both transfontanellar ultrasound and magnetic
      resonance imaging. It is proposed that the antenatal demonstration of an
      echogenic linear structure running within the third ventricle is a specific sign
      of lobar holoprosencephaly, and can assist this difficult diagnosis.

PMID- 12797229
TI  - Fetal arachnoid cyst: report of two cases.
AB  - Two new cases of antenatal diagnosis of arachnoid cyst are described. Diagnosis
      was made at 2.5 and 32 weeks' gestational age. In the first case, a slight
      increase in the diameter of the anechoic mass was observed in the second
      trimester. In the second case, ventricular dilatation was present prenatally.
      Appropriate surgical therapy was initiated at 2 months in the first case and at 8
      days in the second and the neurological development of the two children is
      considered as normal at 18 months of age. Major features of in utero diagnosis,
      treatment and follow-up are discussed.

PMID- 12797230
TI  - Use of intracavity saline instillation and transvaginal ultrasonography to detect
      tamoxifen-associated endometrial polyps.
AB  - There is sometimes a discrepancy between the apparent thickness of postmenopausal
      endometria, as determined by transvaginal ultrasonography, and the examination of
      endometrial biopsies. We describe a case which showed that tamoxifen (20 mg/day
      over 12 months) decreased impedance to blood flow in the uterine arteries and
      increased the apparent thickness of the endometrium. Conversely, the analysis of
      biopsies suggested the presence of an atrophic endometrium. The introduction of
      sterile saline into the uterine cavity during a repeat ultrasound scan revealed
      the presence of a large, free-floating endometrial polyp, which was subsequently
      difficult to see by hysteroscopy.

PMID- 12797231
TI  - Transvaginal color Doppler in the detection of external iliac vein thrombosis in
      pregnancy.
AB  - A case is described where transvaginal color Doppler was used to demonstrate
      upward external iliac vein extension of thrombus at 26 weeks' gestation.
      Normally, transabdominal color Doppler can visualize the iliac vessels, but in
      advanced pregnancy the uterus obstructs the view. This technique is useful in
      determining of there is a 'high' deep vein thrombosis in pregnancy, and may also
      prove useful in the obese patient.

PMID- 12797232
TI  - Prenatal diagnosis and fetal outcome of cystic adenomatoid malformation of the
      lung: case report and historical survey.
AB  - Diagnostic ultrasound allows prenatal diagnosis of cystic adenomatoid
      malformation of the lung from the second trimester onwards throughout pregnancy.
      If the diagnosis is made before the 24th week of pregnancy, counselling often
      results in termination of pregnancy. Whether or not this attitude is in agreement
      with good medical practice is discussed on the basis of our own experience and a
      review of the literature.

PMID- 12797233
TI  - The effects of tamoxifen on the endometrium.

PMID- 12797234
TI  - Estimated linear relationship between ductus venosus index and gestational age.

PMID- 12797236
TI  - Transvaginal three-dimensional imaging.

PMID- 12797237
TI  - Design and analysis of studies to derive charts of fetal size.

PMID- 12797238
TI  - Investigation and treatment of fetal thyroid diseases.

PMID- 12797239
TI  - The association between an abnormal nuchal skin fold, trisomy 21, and ultrasound
      abnormalities identified during the second trimester of pregnancy.
AB  - Fetal echocardiography and a detailed non-cardiovascular ultrasound examination
      were performed prospectively between 14 and 23 weeks of gestation prior to
      genetic amniocentesis in 2800 consecutive fetuses at increased risk for trisomy
      21 due to advanced maternal age or a low maternal serum alpha-fetoprotein. An
      abnormal nuchal skin fold was defined as >or=6 mm. Of 2800 fetuses, 23 (0.82%)
      had an abnormal nuchal skin fold. Seven of 35 fetuses (20%) with trisomy 21 and
      one of 12 fetuses (8.3%) with trisomy 18 had an abnormal nuchal skin fold. Of the
      23 fetuses with an abnormal nuchal skin fold, seven (30.4%) had trisomy 21, one
      (4.4%) trisomy 18, one (4.4%), 46,XY,11p+ and 14 (60.8%) had normal karyotypes.
      The fetuses with trisomy 18 and 46,XY,11p+ had malformations of the
      cardiovascular and non-cardiovascular organ systems. Five of seven (71%) fetuses
      with trisomy 21 and an abnormal nuchal skin fold had abnormalities of both the
      cardiovascular and non-cardiovascular organ systems; one of seven (14.5%) had a
      heart defect only; and one of seven (14.5%) an abnormality of a non
      cardiovascular organ system. Of the 14 fetuses with an abnormal nuchal skin fold
      and normal karyotype, seven had no additional abnormalities, six an abnormality
      of the heart, and one a non-cardiovascular defect. Fetuses with an abnormal
      nuchal skin fold had a significant increased incidence of trisomy 21 when a
      combination of cardiovascular and non-cardiovascular abnormalities were present
      compared to fetuses with no additional defects or a single defect of the heart or
      non-cardiovascular organ system (p = 0.001). In fetuses with an abnormal nuchal
      skin fold, the incidence of congenital heart disease was 6155, central nervous
      system defects 17%, hyperechoic bowel 8.7%, and renal abnormalities 17.4%. These
      findings would suggest that the fetus identified with an abnormal nuchal skin
      fold with additional cardiovascular and non-cardiovascular abnormalities has a
      greater risk for chromosomal aneuploidy compared to the fetus with an isolated
      abnormal nuchal skin fold or with one additional abnormality of the heart or a
      non-cardiovascular organ system. When an abnormal nuchal skin fold is identified,
      careful evaluation of the fetal cardiovascular system should be made.

PMID- 12797240
TI  - Biometric measurements in fetuses of different race and gender.
AB  - Sonographic fetal biometric measurements on 6082 low-risk patients were compared
      in the second and third trimesters of pregnancy with respect to fetal race and
      gender. Ultrasonic measurements were obtained from fetuses of women participating
      in the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS), who
      underwent both an early sonographic evaluation between 15 and 22 weeks' gestation
      and a later scan between 31 and 35 weeks' gestation. In the 16-21-week scans,
      male fetuses had significantly larger biparietal diameter measurements compared
      to female fetuses (estimated difference 0.852 mm, 95% CI 0.737-0.967). There was
      only minimal difference in biparietal diameter between Black and White fetuses.
      Femur length was similar in both female and male fetuses, but longer in Black
      compared to White fetuses (estimated difference 0.808 mm, 95% CI 0.539-1.078).
      During the 31-35-week scans, male fetuses continued to have larger biparietal
      diameter measurements compared to female fetuses (estimated difference 1.22 mm,
      95% CI 1.04-1.40), and femur lengths were persistently longer in Black compared
      to White fetuses (estimated difference 0.563 mm, 95% CI 0.234-0.893). Further
      investigation is necessary to evaluate the effect of these slight differences in
      morphometric fetal measurements between races and genders, so that we can
      determine how best to use them for optimizing prenatal care.

PMID- 12797241
TI  - Biometry of early pregnancy with transvaginal sonography.
AB  - A prospective cross-sectional study was performed in 248 pregnant women between 5
      and 12 weeks' menstrual age with transvaginal sonography to establish biometric
      charts of the gestational sac, embryonic crown-rump length and biparietal
      diameter, amniotic sac and yolk sac to be used for assessment of gestational age
      and prediction of pregnancy failure. Polynomial regression analysis was applied
      and demonstrated a statistically significant positive correlation that could be
      described in all cases as a quadratic function, between gestational age and all
      the measurements with the exclusion of the yolk sac. Centile charts of both
      growth models and dating models were tabulated. The interrelationship between
      different measurements, including the gestational sac, crown-rump length,
      biparietal diameter and amniotic sac was also evaluated to produce age
      independent charts. The dating model of the crown-rump length was found to have
      mean values similar to those described in transabdominal studies. The 95%
      reference interval was, however, 8.4 days, which was not lower than those
      reported in most transabdominal studies. It was concluded that transvaginal
      sonography was more able than the abdominal route to allow measurement of the
      crown-rump length in very early gestation, but did not yield a greater accuracy
      in predicting gestational age.

PMID- 12797242
TI  - Second-trimester uterine artery flow velocity waveform and oral glucose tolerance
      test as a means of predicting intrauterine growth retardation.
AB  - The absence of a rise in maternal serum glucose level during the course of a 3-h
      glucose tolerance test was noted in pregnancies that resulted in growth-retarded
      infants. It was postulated that this response to an oral glucose load, in
      association with increased impedence to uterine artery blood flow, as
      demonstrated by color flow Doppler waveforms, could select the pregnancies at
      greater risk of developing intrauterine growth retardation. One hundred and four
      uncomplicated primigravidae and 88 multigravid women considered to be at high
      risk of developing intrauterine growth retardation were monitored longitudinally
      from the 24th week of gestation. The right and left uterine artery resistance
      indices (RI) were measured at 24 weeks by means of pulsed Doppler with color flow
      imaging, and the results were averaged. The following week, an oral glucose
      tolerance test (OGTT) was performed. Serum glucose was measured immediately prior
      to the ingestion of 100 g glucose, and again after 60, 120 and 180 min. The OGTT
      results were classified as normal, impaired glucose tolerance, gestational
      diabetes mellitus, and flat. This last result was indicated by a less than 20%
      rise in serum glucose compared to the fasting value.A notch in the uterine artery
      waveform and/or an RI greater than 0.58 (> 2 SD above the mean) was found in 39
      (20.3%) women. A flat response to the OGTT was seen in 31 (16.1%) cases. Of the
      16 women in whom both a high RI and a flat OGTT response curve were demonstrated,
      15 (93.7%) delivered low-birth-weight babies due to intrauterine growth
      retardation. Eight of these 16 women developed hypertension. In the group with a
      flat OGTT response curve but normal uterine artery RI, two of the 15 women
      (13.3%) had growth-retarded babies. The positive predictive value of an increased
      RI with a flat OGTT response curve was 94%, while the predictive values of each
      individual method were 62% and 55%, respectively, for development of intrauterine
      growth retardation.Increased resistance to blood flow in the uteroplacental
      circulation in conjunction with a flat response curve to an oral glucose load
      might identify a group of pregnant women at risk of having a growth-retarded
      infant with or without the development of hypertension.

PMID- 12797243
TI  - Uteroplacental resistance index: analysis of intra- and interobserver
      variability.
AB  - The aim of this study was to assess the intra- and interobserver variability of
      second-trimester uteroplacental continuous-wave flow velocity waveforms. The left
      and right uterine and arcuate resistance indices were measured in women having
      their routine booking scan at 16-24 weeks' gestation. Four experiments assessed
      the intra-observer between-frame variability, the intraobserver beat-to-beat
      variability, the intraobserver temporal variability, and the interobserver
      variability, using the limits-of-agreement method. The intraobserver between
      frame variability was greater than the beat-to-beat variability at three of the
      four sites. The temporal variability was not significantly different between
      sites. There were wide interobserver limits of agreement with respect to the
      reference ranges, although they were greater at arcuate sites than uterine sites.
      These observations suggest that the reproducibility of the resistance index in
      continuous wave Doppler uteroplacental flow velocity waveforms is poor,
      particularly from arcuate sites. The uterine site is preferable and descriptive
      analysis may be better.

PMID- 12797244
TI  - Detection of ovaries by transvaginal sonography in postmenopausal women.
AB  - A total of 230 apparently healthy postmenopausal women underwent transvaginal
      sonography and pelvic examination. The mean ovarian volume was 3.1 cm(3) with a
      range of 0.4-57.4 cm(3) and fewer than 5% (4.8%) of the subjects had a mean
      volume exceeding two standard deviations of the sample mean. Transvaginal
      sonography successfully imaged 64% of reported ovaries overall, although the
      proportion of ovaries imaged varied by sonographer. The poorer imaging rates
      found in this study, as compared with some previous investigations using
      transabdominal sonography, could be due to several factors including the type of
      sonography, the type of sample, the scanning time, and/or the criteria used to
      identify an ovary. Transvaginal sonography offers practical advantages over
      transabdominal sonography, but the potential loss in sensitivity, due to non
      visualization of a substantial proportion of ovaries, must be formally assessed
      before adopting transvaginal sonography more widely as the primary screening
      modality.

PMID- 12797245
TI  - Vaginal ultrasonography in patients with postmenopausal bleeding.
AB  - Our objective was to define a subset of women with postmenopausal bleeding in
      whom the accepted practice of endometrial sampling could be safely omitted.
      Vaginal endosonographic measurements were compared to the histological findings
      of curettings following diagnostic dilatation and curettage in 129 women with
      post-menopausal bleeding who were not receiving hormonal therapy. Atrophy was
      diagnosed in 49%, slight proliferation in 10%, endometrial polyps in 11%,
      hypoplasia in 12%, and adenocarcinoma in 12%. Endometrial atrophy was associated
      with a mean sonographic thickness of 2.6 mm of the double layer (range 0-6.5 mm).
      Of the women with a final histological diagnosis of atrophy, 92% had an
      endometrial thickness of 3 mm or less. Furthermore, all women with a sonographic
      endometrial thickness of 3 mm or less had atrophic endometrium (p < 0.0001). An
      endometrial thickness of 3 mm or less would have reduced the number of dilation
      and curettage procedures by 45% and no cases of endometrial pathologies would
      have been missed. In women presenting with postmenstrual bleeding, meticulous
      scanning of the endometrium can select a group where endometrial sampling can be
      omitted from the protocol.

PMID- 12797246
TI  - Relapse of maternal thyrotoxicosis presenting as a second-trimester fetal goiter.
AB  - A large fetal goiter was detected at 22 weeks of gestation during an antenatal
      ultrasound scan of a woman with a previous history of Graves' disease treated by
      partial thyroidectomy. This unsuspected finding initiated maternal investigations
      and treatment. In untreated cases poor fetal outcome is common and unfortunately
      fetal thyrotoxicosis/thyroid enlargement frequently remains unrecognized in the
      first pregnancy. We report the case and its management and discuss the literature
      emphasizing the importance of screening for antibodies in the 'at-risk' women and
      the increasing importance of ultrasound in the evaluation and follow-up of these
      patients. Reports of thyrotoxic fetal goiters are extremely rare and, to our
      knowledge, there have been no previous reports of this in the second trimester.

PMID- 12797248
TI  - Detection of ovarian cancer.

PMID- 12797247
TI  - Prenatal ultrasound diagnosis of a rare occurrence of lethal multiple pterygium
      syndrome in two siblings.
AB  - We report two cases of prenatal ultrasound diagnosis of the lethal form of
      multiple pterygium syndrome in successive pregnancies in the same woman. This
      extremely rare entity is characterized by multiple pterygia, flexion
      contractures, facial anomalies and hypoplasia of heart and lungs. The appearance
      of the congenital cataract is unique and this finding was present in both
      abortuses. Prenatal detection of this syndrome is feasible, and an ultrasound
      survey should be offered during genetic counselling to previously affected
      couples.

PMID- 12797250
TI  - The Second International Meeting of the European Society of Endosonography in
      Gynaecology and Obstetrics (ESEGO).

PMID- 12797251
TI  - Routine obstetric ultrasound.

PMID- 12797252
TI  - Early screening for fetal cardiac anomalies.

PMID- 12797253
TI  - Early diagnosis of fetal congenital heart disease by transvaginal
      echocardiography.
AB  - Fetal echocardiography was performed using a high-frequency vaginal ultrasound
      probe in 114 singleton pregnancies between 11 and 16 weeks of gestation. The four
      chamber view with both atria, atrioventricular valves and ventricles as well as
      the origin and double-crossing of aorta and pulmonary trunk could always be
      demonstrated from the 13th week onwards. In 12 of 13 cases, cardiac malformations
      were diagnosed in the first trimester. Only in one case was transabdominal
      echocardiography necessary at 20 weeks to make the diagnosis. In several cases,
      however, additional malformations were overlooked, in particular anomalies of the
      great arteries, such as coarctation of the aorta. Therefore, the accuracy of
      second-trimester transabdominal echocardiography is markedly higher. Because of
      the lower diagnostic accuracy, the high costs of equipment and the high training
      demanded of the examiner, first-trimester transvaginal echocardiography should be
      restricted to the high-risk fetus, i.e.: (1) Cases with other fetal anomalies
      very often associated with cardiac defects, such as nuchal edema and hygroma, non
      immune hydrops, omphalocele, situs, inversus, or persisting arrythmia; (2) High
      risk families with one or more first-degree relatives with cardiac defects are
      either inherited by Mendelian rules alone, or as part of a rare syndrome; and (3)
      In pregestational diabetes of the mother.Thus, many severe cardiac defects can be
      detected or excluded in the first trimester, reducing maternal anxiety. In these
      high-risk cases, second-trimester echocardiography using the transabdominal route
      should always be performed because of its distinctly higher diagnostic accuracy.

PMID- 12797254
TI  - Sonography of fetal agenesis of the corpus callosum: a survey of 35 cases.
AB  - Agenesis of the corpus callosum was identified by ultrasound examination in 35
      fetuses between 19 and 37 weeks' gestation. The ultrasound findings included
      absence of the corpus callosum and cavum septum pellucidum (hypoplasia in one
      case of partial agenesis of the corpus callosum), a typical 'teardrop'
      configuration of the lateral ventricles, distension of the interhemispheric
      fissure, upward displacement of the third ventricle, radiate arrangement of the
      medial cerebral gyri, and abnormal branching of the anterior cerebral artery.
      Associated anomalies were identified in 20 fetuses, including heterogeneous
      malformations and chromosomal aberrations (mosaic-trisomy 8 in three, trisomy 18
      in two and partial duplication 8p in one). Five cases of agenesis of the corpus
      callosum were identified in a population of pregnant patients prospectively
      investigated because of genetic risk for agenesis of the corpus callosum or
      related syndromes. In this group, no diagnostic errors were made. Long-term
      neurological follow-up (6 months to 11 years) was available in 11 infants with
      antenatal diagnosis of isolated agenesis of the corpus callosum. Normal
      intellectual development was present in nine, and a low intellect (developmental
      quotient between 70 and 85) was found in two. It is concluded that fetal agencies
      of the corpus callosum is associated with elusive sonographic findings that can,
      however, be accurately identified by targeted examinations. In routine sonograms,
      an increased atrial width and/or failure to visualize the cavum septum pellucidum
      should arise the suspicion of fetal agencies of the corpus callosum. Given the
      high frequency of associated anomalies, prenatal diagnosis of agencies of the
      corpus callosum dictates the need for a careful survey of fetal anatomy and
      karyotyping. The prognosis is isolated agencies of the corpus callosum remains
      uncertain, although it is expected that a normal or boarderline intellectual
      development will occur in many cases.

PMID- 12797255
TI  - Fetal hyperechogenic bowel and Down's syndrome.
AB  - Hyperechogenic bowel was identified among 55 of 6781 (0.81%) fetuses prior to
      second-trimester genetic amniocentesis. Trisomy 21 was found in eight of the 55
      (14.5%) fetuses identified with hyperechogenic bowel compared to 60 of 6726
      (0.89%) fetuses with normal bowel echogenicity (p < 0.001). Hyperechogenic bowel
      carried a 16-fold greater risk for Down's syndrome than normal bowel echogenicity
      (relative risk 16.8, 95% confidence intervals 8.2-32.5). Chromosome abnormalities
      other than trisomy 21 were found in four additional fetuses with hyperechogenic
      bowel (two triploid and one each with 47,XXX; 45,X/47,XXX mosaicisim). Combining
      these four cases with the eight fetuses having trisomy 21, 21.8% (12 of 55) of
      fetuses with hyperechogenic bowel proved to have a chromosome abnormality. We
      conclude that hyperechogenic bowel is associated with chromosome abnormalities,
      particularly Down's syndrome, when detected during the second trimester.

PMID- 12797256
TI  - Sonographic findings and fetal chromosomal studies undertaken prenatally by fetal
      blood sampling using cordocentesis.
AB  - Prenatal karyotyping was carried out on 206 pregnancies with sonographic
      abnormalities, including fetal malformations, growth retardation and disorders of
      the amniotic fluid volume. Overall, chromosomal aberrations were detected in 37
      cases (18.0%), but the frequency of chromosomal aberrations was 8.2% in fetuses
      with a single anomaly and 52.7% in fetuses with multiple anomalies. The
      chromosomal risk was very high in malformations associated with growth
      retardation (81.8%) or with both growth retardation and disorders of the amniotic
      fluid volume (82.4%). High rates of chromosomal aberrations were observed in
      cases of heart anomalies, diaphragmatic hernia, urinary tract obstruction,
      hydrocephalus, intestinal atresia, abdominal wall defect and fetal
      effusion/hydrops. In fetuses at high risk of chromosomal aberrations,
      cordocentesis for rapid karyotyping is justified in the second or third
      trimester.

PMID- 12797257
TI  - Ductus venosus index: a method for evaluating right ventricular preload in the
      second-trimester fetus.
AB  - This study was designed to examine ventricular preload by measuring the ductus
      venosus index during the second trimester of pregnancy. A total of 137 women were
      entered into the study. Each fetus was examined with real-time, color and pulsed
      Doppler ultrasound. The color Doppler maximal velocity setting was adjusted so
      that the umbilical vein was homogeneous in color, did not demonstrate aliasing,
      and filled the venous lumen. The pulsed Doppler gate was placed within the ductus
      venosus in all subjects. Color Doppler identified a turbulent flow velocity
      within the ductus venosus which was not present in the umbilical vein, hepatic
      vein or inferior vena cava. The ductus venosus pulsed Doppler waveform
      demonstrated flow velocity from the umbilical vein to the heart during
      ventricular systole, the rapid filling phase of ventricular diastole, and atrial
      systole. However, flow velocity was decreased during atrial systole compared to
      ventricular systole and the rapid filling phase of diastole. The ductus venosus
      index was computed from the Doppler waveform of the ductus venosus at points
      consistent with ventricular and atrial systole ((ventricular systole - atrial
      systole)/ventricular systole). Regression analysis demonstrated a significant (p
      = 0.001) relationship between the ductus venosus index and gestational age
      (ductus venosus index = 75.5757 - 7.25484 x weeks gestation), standard error of
      the estimate = 7.21959; R = -0.451. One fetus with a hypoplastic left atrium and
      ventricle demonstrated a normal ductus venosus index. Two fetuses, one with
      pulmonary atresia and the second with severe cardiovascular dysfunction,
      demonstrated an abnormal ductus venosus index associated with absent flow
      velocity during atrial systole. This was associated with notching in the
      umbilical vein. The ductus venosus index is an angle-independent measurement from
      which right ventricular preload may be evaluated.

PMID- 12797258
TI  - Outcome of twin gestations following sonographic demonstration of two heart beats
      in the first trimester.
AB  - We conducted a prospective study to assess pregnancy outcome following a first
      trimester ultrasound examination demonstrating intrauterine twins with heart
      beats. Our study population included 68 cases of twin gestations in which a first
      trimester scan demonstrated two heart beats. We correlated pregnancy outcome with
      placentation type, gestational age, maternal age, and method of conception. There
      were 59 dichorionic and nine monochorionic gestations. Twenty-six of the
      dichorionic pregnancies resulted from treatment for infertility. Among all 68
      cases, 54 (79%) delivered viable twins, eight (12%) delivered one infant, and six
      (9%) delivered none. The outcome in dichorionic gestations (83% delivered twins,
      12% singletons, 5% none) was significantly better than in monochorionic
      gestations (56%, 11%, 33%, respectively) (p < 0.05). Among dichorionic twins,
      pregnancy outcome was worse in twins initially identified on a 6-7.9 week
      ultrasound examination (74% delivered twins, 21% singletons, 6% none) as compared
      to those identified at 8-13 weeks (96%, 0%, 4%, respectively) (p < 0.05). The
      outcome in dichorionic gestations was worse in women over 35 compared to those
      under 35 (p < 0.05), and those with treatment for infertility compared to those
      who conceived naturally (p = 0.05). These results provide prognostic information
      about outcome of twin pregnancies scanned in the first trimester as a function of
      chorionicity, gestational age, maternal age, and method of conception.

PMID- 12797259
TI  - Intraobserver reliability of amniotic fluid volume estimation by two techniques:
      amniotic fluid index vs. maximum vertical pocket.
AB  - We evaluated the intraobserver agreement of two techniques of amniotic fluid
      assessment: amniotic fluid index and maximum vertical pocket. The intraobserver
      variation of the two forms of amniotic fluid assessment was obtained by
      evaluating amniotic fluid prior to fetal biometry (post-biometry value) and after
      fetal biometry (pre-biometry value). Between January and June 1990, this amniotic
      fluid assessment was by the maximum vertical pocket technique, and between July
      and December 1990, by the amniotic fluid index technique. In the Grace Maternity
      Hospital, Vancouver, 352 subjects were evaluated by the maximum vertical pocket
      technique, and 184 subjects by the amniotic fluid index technique.Amniotic fluid
      volumes were categorized into normal, oligohydramnios, and polyhydramnios, and
      the pre-biometry and post-biometry categories of amniotic fluid index and maximum
      vertical pocket techniques were compared by kappa statistics. The maximum
      vertical pocket technique showed poor intraobserver agreement (kappa = 0.33), but
      the amniotic fluid index technique showed good agreement (kappa = 0.72). With the
      poor reproducibility of the maximum vertical pocket technique in assessing
      extremes of amniotic fluid volume, it is difficult to support its use as a
      component of fetal assessment.

PMID- 12797260
TI  - Predictive value of transvaginal uterine Doppler assessment in an in vitro
      fertilization program.
AB  - This study evaluates the prognostic value of uterine Doppler performed on the day
      of embryo transfer in an in vitro fertilization program. Patients were divided
      into two groups according to the type of ovarian stimulation. The Doppler
      investigation was carried out using vaginal sonography. The pulsatility index was
      used to evaluate the uterine blood flow pattern. The hormonal profile (estradiol,
      luteinizing hormone (LH) and progesterone) was correlated to Doppler results and
      to the pregnancy rate. The comparison between patients treated with analogs and
      those who were not shows a significant difference in their hormonal profile. In
      the first group, we found a higher estradiol and progesterone serum
      concentration. The LH level and the pulsatility index were statistically lower.
      The endometrium was thicker in patients treated with gonadotropin releasing
      hormone agonists. In the group of patients treated with analogs, the statistical
      analysis showed no significant difference in the mean pulsatility index value in
      women who achieved a pregnancy and in those who failed. In the group of patients
      who received no agonists, only one variable was significantly different: the mean
      age was lower in women who became pregnant. We observed no ongoing pregnancy in
      women who had a pulsatility index value higher than two standard deviations
      (pulsatility index = 3.55). We therefore suggest the use of this value as a
      threshold. Thus, if a patient has a high uterine artery impedance,
      cryopreservation should be used and embryo transfer should be postponed to a
      subsequent cycle, or embryo transfer delayed for a few days using co-culture.
      This study clearly shows the impact of hormonal response on the Doppler value and
      on the pregnancy rate. However, the use of a threshold value for uterine artery
      pulsatility index might have a clinical impact in the future management of
      patients attending an in vitro fertilization program.

PMID- 12797261
TI  - Doppler studies of uterine arteries in spontaneous and artificially induced
      menopausal women.
AB  - In the postmenopausal period, women's genital organs undergo several changes and
      female hormones, as well as modification of vascular reactivity to various
      stimuli, play a major role in this process. We studied the modification of
      uterine vascularity consequent to spontaneous or artificially induced menopause,
      with gonadotropin releasing hormone (GnRH) analogs. Flow velocity waveforms of
      the uterine arteries were detected using a color Doppler imaging system with a
      transvaginal probe; the pulsatility index was calculated. The study group
      consisted of 15 women observed before and after 6 months of treatment with GnRH
      analogs (triptorelin 3.75 mg depot every 4 weeks intramuscularly) for uterine
      fibromyomata; 20 women after 5 years of spontaneous menopause; and 20 healthy and
      normally menstruating women in the late luteal phase. We found a significant
      difference among the three groups with a progressive increase of the pulsatility
      index in spontaneous menopausal women. This phenomenon may be due to a different
      hormonal pattern which exists in spontaneous and artificially induced menopause
      (increase of gonadotropin level in the former and decrease in the latter), and to
      a decrease of vascular compliance caused by progressive sclerosis of the vasal
      walls.

PMID- 12797262
TI  - Methotrexate treatment of unilateral twin ectopic pregnancy: case report and
      pharmacokinetic considerations.
AB  - We describe a case of spontaneous twin ectopic pregnancy, managed with the
      combination of local injection under ultrasound control and intramuscular
      administration of methotrexate. We describe a difference between the area under
      the curve of declining plasma concentration of methotrexate after intramuscular
      and local injection.

PMID- 12797263
TI  - Fetal hydrometrocolpos.
AB  - This report describes a case of hydrometrocolpos presenting antenatally as a
      cystic mass arising from the pelvis of a female fetus. The baby was born at 33
      weeks and died within an hour due to pulmonary hypoplasia. Postmortem examination
      demonstrated hydrometrocolpos, dense adhesions in the abdomen and pulmonary
      hypoplasia.

PMID- 12797265
TI  - Prenatal diagnosis of central nervous system anomalies - 20 years after.

PMID- 12797264
TI  - Fetal eye movements.
AB  - Since 1981, when eye movements of the human fetus were first reported, the study
      of fetal eye movements has increased, mainly focusing on the ontogenesis of eye
      movements and as one parameter of behavioral states. Using real-time ultrasound,
      fetal eye movements can be clearly observed from 14 weeks of gestational age.
      Fetal eye movements may be described in terms of their pattern, frequency and
      incidence of periods containing eye movements and no eye movements. Furthermore,
      the relationship of eye movements to other behaviors may be used to give
      information on the integration of central nervous system function. A picture of
      normal fetal eye movements can be constructed and used to detect abnormalities in
      eye movements which can indicate underlying abnormalities of the central nervous
      system. This paper concludes that, although in its early stages, the study of
      fetal eye movements holds promise for a greater understanding of brain
      development and the assessment of the condition of the fetus.

PMID- 12797266
TI  - Correlation of umbilical Doppler features and placental morphometry: the need for
      uniform methodology.

PMID- 12797267
TI  - Doppler velocimetry, placental morphology and outcome in insulin-dependent
      diabetes.
AB  - The purpose of this study was to determine the underlying cause of abnormal
      umbilical artery Doppler velocimetry in pregnancies complicated by insulin
      dependent diabetes, by evaluating placental morphology and correlating Doppler
      results with pregnancy outcome. Our study population consisted of 14 pregnancies
      with normal Doppler results and 11 pregnancies with abnormal Doppler results.
      Quantitative placental examinations were performed. Maternal and perinatal
      characteristics were analyzed. Infants from the abnormal Doppler group had a
      statistically significantly higher incidence than those from the normal Doppler
      group of hyperbilirubinemia, Cesarean delivery for fetal distress, and neonatal
      intensive care stay of 2 or more days. Women with abnormal Doppler results
      delivered earlier (36 vs. 38 weeks) and had infants of lower birth weight (3079
      vs. 3629 g). They were also three times more likely to have poor glycemic control
      (relative risk = 3.2; p = 0.0067). The placentae of both groups showed no
      statistically significant differences in placental weight, number of tertiary
      stem villi, number of small muscular arteries, or mean arterial width. Our
      findings suggest a functional rather than structural placental process as the
      cause of the abnormal Doppler results in pregnancies complicated by diabetes. An
      association between glycemic control and Doppler velocimetry is suggested.

PMID- 12797268
TI  - Correlation of Doppler and placental immunohistochemical features in normal and
      intrauterine growth-retarded fetuses.
AB  - The aim of this study was to correlate and compare Doppler and anatomical
      placental findings obtained from 48 normal and 35 intrauterine growth-retarded
      (IUGR) fetuses. The IUGR group consisted of 19 fetuses from pregnancies
      complicated by pre-eclampsia and 16 from healthy mothers. Color Doppler
      evaluation of umbilical, spiral and uterine arteries was performed. Placental
      specimens from both normal and growth-retarded fetuses were obtained at the time
      of delivery. Placental specimens were evaluated using histochemical and
      immunohistochemical techniques. A progressive decrease in the pulsatility index
      was observed in umbilical, spiral and uterine arteries throughout pregnancy in
      the normal-growth fetuses. High umbilical artery pulsatility index values were
      obtained in 29 out of the 35 growth-retarded fetuses, six of them showing absent
      or reversed end-diastolic umbilical artery flow pattern. A total of 13 IUGR
      fetuses showed high resistance uterine artery flow velocity waveforms. Increased
      pulsatility index values were obtained from the spiral arteries of 16 growth
      retarded fetuses. Abnormal histological and histochemical placental patterns were
      observed in all the growth-retarded fetuses with umbilical artery Doppler
      abnormalities. The presence of a peculiar dendritic cell subpopulation, strongly
      resembling the Langerhans cells, expressing the HLA-DR+/CD1+ phenotype, was
      detected in all growth-retarded fetuses, whether there was maternal pathology or
      not. Our data show uterine and spiral artery data as being ineffective in the
      monitoring of IUGR fetuses. The placental extracellular matrix seems to play an
      important role in the regulation of the umbilical circulation. The presence of
      CD1+ cells as a sign of a possible immunological mechanism in the pathogenesis of
      the intrauterine growth retardation is discussed.

PMID- 12797269
TI  - Single umbilical artery: a Doppler flow velocity study of four cases.
AB  - We measured the pulsatility index of the umbilical artery in four fetuses
      identified as having a single umbilical artery. A pulsed color Doppler ultrasound
      machine was used and measurements were performed at 4-week intervals following
      the first diagnosis of single umbilical artery (week 22-34). The pulsatility
      index was derived from the mean of five consecutive measurements at the umbilical
      insertion of the cord, taking care to obtain the Doppler signal with an incidence
      angle between +45 degrees and -15 degrees. All measurements were taken during
      periods of fetal inactivity. The pulsatility index at 22, 26, 30, 34 and 38 weeks
      in these pregnancies did not differ significantly from the mean values registered
      in normal pregnancies. The four women gave birth to babies of normal weight: two
      were healthy, one suffered from bladder extrophy and hemispondyly, the other had
      bilateral dilatation of the renal pelves, megalocystis, megalourethra and an
      imperforate anus.

PMID- 12797270
TI  - Abnormal membranes in obstetrical ultrasound: incidence and significance of
      amniotic sheets and circumvallate placenta.
AB  - Amniotic sheets were identified in ten of 1784 patients having routine obstetric
      ultrasound scans, giving an incidence of 0.6%. In the same population, findings
      suggesting circumvallate placenta were seen in three patients, giving an
      incidence of 0.2%. The overall frequency of finding abnormal membranes projecting
      into the gestational sac was 0.8% which is an order of magnitude greater than the
      incidence of amniotic bands, which are only present in up to 0.08% of
      pregnancies. It is important to distinguish amniotic sheets and circumvallate
      placenta from amniotic bands, since they are much more likely to be found during
      the ultrasound examination and need to be properly identified so as to avoid
      needlessly alarming pregnant patients or inappropriately considering termination
      of pregnancy for relatively benign entities.

PMID- 12797271
TI  - Fetal acidosis and Doppler velocimetry of the umbilical arteries in labor.
AB  - The objective of the study was to determine whether Doppler velocimetry indices
      of the fetal umbilical arteries change with the development of acidosis during
      labor. Repeated Doppler velocimetry was performed in selected patients with high
      risk labors for the purpose of evaluating whether this might be a useful test of
      fetal well-being in labor. The study sample comprised 36 women with singleton
      pregnancies, complicated either by gestational proteinuric hypertension or by
      intrauterine growth retardation (or both) with a normal cardiotocographic tracing
      at the onset of labor. The acid-base status of the fetus was assessed after
      delivery by analyzing the umbilical artery blood. A total of 27 fetuses were
      followed through labor. Six were born with an umbilical artery base deficit of
      more than 10 mmol/l. No change in mean Pourcelot ratio (resistance index) was
      noted in both normal and acidotic fetuses. None of the acidotic fetuses showed a
      change in Pourcelot ratio of more than 0.03. We conclude that Doppler velocimetry
      of the umbilical arteries, as measured by the Pourcelot ratio, does not
      contribute to the diagnosis of fetal acidosis in labor.

PMID- 12797272
TI  - Doppler flow velocity waveforms in late first- and early second-trimester
      fetuses: reproducibility of waveform recordings.
AB  - The objective of the study was to assess the reproducibility of Doppler flow
      measurements of the fetal umbilical vein and artery, descending and ascending
      aorta, mitral and tricuspid valve, pulmonary artery, inferior vena cava and
      ductus venosus in early pregnancy. In a cross-sectional study, Doppler
      measurements were obtained in a total of 54 women at 11-16 weeks of gestation, at
      2-5 different vascular sites, on 3-5 different occasions, at 5-min time
      intervals. The total variance in the various flow velocity parameters was
      partitioned in a between-subject and within-subject component by analysis of
      variance, and, from these calculations, coefficients of variation in waveform
      recording were calculated. Flow velocity waveform recording was characterized by
      coefficients of variation in the range 2.2-5.7% except for the acceleration time
      (18.6-24.5%) and percentage reverse flow (8.8%). In conclusion, our data suggest
      that fetal flow velocity waveforms in early pregnancy demonstrate good
      reproducibility in the individual subject, while all parameters depict larger
      variabilities for between-subject values. Acceleration time turned out to be
      poorly reproducible. If a single flow velocity waveform measurement is used for
      the future evaluation of clinical conditions in early pregnancy, one has to
      consider that normal values will display a rather wide range.

PMID- 12797273
TI  - Laser surgery under sonographic control: preliminary experimental investigations.
AB  - The laser has gained increasing importance during recent years as a useful
      addition to the physician's therapeutic armoury. Reports on successful
      prostatectomy by ultrasound-guided laser coagulation in an animal model
      encouraged us to evaluate the possibility of using this technique for
      gynecological indications (for example, ectopic pregnancy, endometriosis, ovarian
      cysts, and other areas of medicine). We used two different laser systems. The
      devices consisted of a real-time abdominal scanner (4-5 MHz) or a transvaginal
      sector scanner (5-7.5 MHz) coupled to a neodymium : YAG laser with a 1064 nm
      wavelength or a holmium : YAG laser with 2120 nm wavelength. An experimental set
      up using a water bath revealed clear visibility of the fiber tip and the laser
      irradiation in real-time ultrasound at 7.5 MHz. Subsequently, a needle (routinely
      used in transvaginal puncture of ectopic pregnancy) was placed in animal and
      human tissue specimens and the laser fiber was inserted. The tissue was exposed
      to both laser systems at different energy densities, pulse rates and pulse
      widths. The sonographic appearance was recorded and correlated with the
      macroscopic findings. Results indicate that the holmium : YAG laser at a pulse
      rate of 5 Hz and a power of 2 watts is effective in removing substantial amounts
      of tissue. Moreover, it offers immediate visualization and control of the damaged
      area by producing a strongly echogenic focus. The neodymium : YAG laser showed
      comparatively poorer sonographic visibility and a precarious thermal mode of
      action, which are important considerations influencing its applicability. The
      holmium : YAG laser system with its non-thermal mode of action seems promising
      for the further clinical application of ultrasound-guided laser surgery.

PMID- 12797274
TI  - Characteristics of blood flow in cancer of the uterine cervix.
AB  - Blood flow characteristics were measured in patients with histologically proved
      cervical cancer and compared to normal values. Flow parameters were derived by
      color and pulsed Doppler ultrasound. The results showed a significant difference
      in the mean values of resistance index and pulsatility index among the diseased
      patients and healthy controls. However, the method does not have the required
      sensitivity for screening purposes, so that its value may mainly be in the follow
      up of patients treated conservatively with radiation and chemotherapy.

PMID- 12797275
TI  - Ectopic pregnancy: transvaginal sonographic findings of 152 cases.
AB  - In a retrospective study performed on 152 cases of verified ectopic pregnancy,
      the features at transvaginal sonography were evaluated. A total of 146 (96%) of
      the patients had at least one abnormal sonographic feature and pelvic/cul-de-sac
      fluid was the most common finding, detected in all of the 146 patients.
      Pelvic/cul-de-sac fluid was particulate in 103 patients and simple in 43.
      Pelvic/cul-de-sac fluid together with extrauterine findings were found to be
      present in 93.8% (137/146) of the patients, suggesting the fact that if
      pelvic/cul-de-sac fluid was detected, every effort should be made to image the
      tube. The extrauterine transvaginal sonographic features included 102 (63.0%)
      patients with a mass, 60 (41.1%) with a gestational sac (with or without yolk sac
      or embryo), and eight (5.3%) with a living embryo. Comparison of the sonographic
      findings according to the status of the ectopic pregnancy revealed that
      particulate fluid (98.9%), and an extra-uterine mass (88.2%) were the features
      that aided in the diagnosis of ruptured and aborted ectopic pregnancies, whereas
      an extrauterine gestational sac (72.9%), and a living embryo (11.9%) were
      associated with intact ectopic pregnancies. Our findings support the practice of
      using transvaginal sonography, and ss-human chorionic gonadotropin measurements
      in the diagnosis and prediction of the status of ectopic pregnancy.

PMID- 12797276
TI  - Antenatal diagnosis of vasa previa by transvaginal color Doppler sonography.
AB  - Vasa previa is a rare complication of pregnancy with a high perinatal mortality,
      which has virtually not changed over the last 200 years. In this case report we
      describe the use of color Doppler ultrasonography to make a correct antepartum
      diagnosis of vasa previa. The baby was delivered by Cesarean section. A strategy
      is presented which may reduce the high mortality rate from this condition.

PMID- 12797277
TI  - Aggressive direct treatment of a fetus with supraventricular tachycardia and
      hydrops fetalis.
AB  - We report a case, in which direct fetal therapy by amiodarone injected into the
      umbilical vein during the last trimester of pregnancy was used for the treatment
      of fetal supraventricular tachyarrhythmia in the presence of severe hydrops
      fetalis. Eight injections were needed due to the recurrence of supraventricular
      tachycardia 1-9 days after the initial normalization of fetal tachycardia after
      each puncture. A severe fetal hydrops was maintained despite the achievement of
      sinus rhythm, and thus two ascites draining procedures were performed during the
      last 3 days before delivery to expand the fetal lungs. A normorhythmic hydropic
      baby was born by Cesarean section at 34 weeks + 6 days. Only mild respiratory
      difficulties occurred after birth. Her electrocardiogram suggests a Wolff
      Parkinson-White syndrome but the overall recovery has been uneventful.

PMID- 12797278
TI  - Development of the Eagle-Barrett (prune belly) syndrome and a thickened, poorly
      functional bladder wall after early second-trimester decompression of fetal
      megacystis.
AB  - The management of bladder outlet obstruction in the fetus remains a debated
      issue. Recent data suggest the use of cystocentesis for the possible relief of
      the bladder neck obstruction or for the opening of posterior urethral valves.
      This case report adds further support for the use of cystocentesis and
      observation prior to the placement of an indwelling bladder shunt. The case
      further demonstrates that relief of the megacystis may not prevent prune belly
      syndrome, bladder dysfunction or renal damage. Finally, the case demonstrates
      that severe oligohydramnios in the second trimester need not invariably result in
      pulmonary hypoplasia.

PMID- 12797279
TI  - International perspectives on safety and standardization of diagnostic pulsed
      ultrasound in medicine.

PMID- 12797290
TI  - Blood flow velocity in the uterine and ovarian arteries during the normal
      menstrual cycle.
AB  - Twelve healthy women with regular menstrual cycles were examined with a
      combination of two-dimensional real-time ultrasound and color and spectral
      Doppler techniques on cycle days 4 and 8 and daily from cycle day 12 until
      follicular rupture, then days + 1, +2, +5, +7 and +12 after follicular rupture.
      The uterine and subendometrial arteries, arteries in the ovarian stroma and
      hilum, in the wall of the largest follicle of each ovary, and in the wall of the
      corpus luteum were examined. The pulsatility index and the time-averaged maximum
      velocity were calculated. In the uterine arteries the pulsatility index was
      highest on day + 2, after which it decreased successively to its lowest value,
      whereas the time-averaged maximum velocity reached its highest value on day + 12.
      Similar changes were observed in the subendometrial arteries. In the non-dominant
      ovary, neither the pulsatility index nor the time-averaged maximum velocity
      manifested any consistent changes during the cycle. In the dominant ovary, the
      time-averaged maximum velocity increased and the pulsatility index decreased
      after follicular rupture, being significantly higher and lower, respectively, in
      the luteal than in the follicular phase. These changes were seen in the ovarian
      hilum, stroma and follicular wall, but were most obvious in the wall of the
      dominant follicle and of the corpus luteum. We conclude that the blood
      circulation in the uterus and in the dominant ovary changes considerably during
      the menstrual cycle, whereas that in the non-dominant ovary shows no unequivocal
      changes.

PMID- 12797291
TI  - Transvaginal ultrasound diagnosis of twin reversed arterial perfusion syndrome at
      9 weeks' gestation.
AB  - Diagnosis of twin reversed arterial perfusion syndrome was made using
      transvaginal sonography at 9 weeks' gestation. The morphological evaluation of
      the abnormal twin revealed a dysmorphic cephalic pole and absence of the upper
      extremities. There was diffuse subcutaneous edema and no detectable cardiac
      activity. The other twin had a normal appearance and a size compatible with the
      gestational age. The fetuses were divided by a thin amniotic membrane with normal
      amniotic fluid in both sacs. Diagnosis was confirmed by demonstrating fetal
      growth and lower limb activity in the abnormal twin 10 days later.

PMID- 12797292
TI  - Lethal multiple pterygium syndrome. The importance of fetal posture in mid
      trimester diagnosis by ultrasound: discussion and case report.
AB  - Lethal multiple pterygium syndrome and its variants provide an opportunity for
      prenatal diagnosis using mid-trimester ultrasound examination. The case presented
      here highlights the importance of postural deformity in reaching a diagnosis and
      illustrates the importance of full ultrasound examination of the fetus even when
      the well-documented common features of a condition are absent.

PMID- 12797293
TI  - Transvaginal ultrasonography in the diagnosis of primary ovarian pregnancy: case
      report.
AB  - This case report describes the sonographic appearance of an ovarian pregnancy; at
      7 weeks of gestation, transvaginal ultrasonography revealed an enlarged left
      ovary containing the gestational sac, yolk sac, and embryonic structures without
      heart activity. High-frequency transvaginal ultra-sound examination proved a
      useful diagnostic tool in this case of ovarian pregnancy.

PMID- 12797294
TI  - Hemodynamic interpretation of the arterial Doppler waveform.

PMID- 12797295
TI  - The fetal examination.

PMID- 12797296
TI  - Borderline fetal cerebral ventriculomegaly - the Twilight Zone.

PMID- 12797297
TI  - Psychological strain experienced by ultrasound staff.

PMID- 12797298
TI  - Fetal mild idiopathic lateral ventriculomegaly: is there a correlation with fetal
      trisomy?
AB  - Mild idiopathic lateral ventriculomegaly in the mid-trimester fetus can be
      accurately detected using modern prenatal ultrasonography. Since an abnormal
      karyotype has been reported in some of these cases, the present prospective study
      was designed to evaluate, first, the prevalence of mild idiopathic lateral
      ventriculomegaly in the general obstetric population and, second, to determine
      the incidence of abnormal fetal karyotype associated with mild idiopathic lateral
      ventriculomegaly. Eight cases of mild idiopathic lateral ventriculomegaly (0.15%)
      were detected among 5400 routine prenatal sonographic examinations, between 16
      and 22 weeks' gestation. Three newborn infants were found to be normal; in one
      baby, spontaneous resolution of the lesion occurred in utero, and, among the
      other five cases, two had an abnormal karyotype: one had Down's syndrome, and one
      trisomy 18. A review of the English literature revealed that 12% of fetuses with
      mild idiopathic lateral ventriculomegaly have an abnormal karyotype. Since 3% of
      the fetuses with Down's syndrome can be visualized in utero with mild idiopathic
      lateral ventriculomegaly, the calculated risk for Down's syndrome when such
      lesions appear is about 3%. We, therefore, conclude that karyotypic study is
      warranted in the mid-trimester fetus with incidental findings of mild idiopathic
      lateral ventriculomegaly.

PMID- 12797299
TI  - Intrathoracic cardiac position in the fetus.
AB  - In a 4-year period, 83 fetuses have been noted to have an abnormal fetal heart
      position within the thorax on fetal echocardiography. In 55 cases where the heart
      lay in the right chest, this was due to the presence of a left-sided
      diaphragmatic hernia; in one case, the heart was abnormally far into the left
      chest because of a left-sided diaphragmatic hernia. Of the remaining 27 cases,
      the heart lay in the right chest in 16 cases. In seven of those 16, there was a
      congenital heart malformation; in six, there were lung anomalies; a hiatus hernia
      was present in one; both congenital heart disease and lung abnormality were
      present in one and one fetus had isolated dextrocardia. In nine cases, the heart
      lay in the center of the chest and in three, the heart lay further to the left
      than normal. Congenital heart disease was found in nine of these 12. Chromosomal
      anomalies were found in four of the 27 cases with an abnormal heart position but
      an intact diaphragm. In summary, it is important to be familiar with the normal
      cardiac orientation within the thorax and to investigate abnormalities of
      position. A diaphragmatic hernia will be the most common underlying cause but,
      where the diaphragm is intact, other explanations must be sought in order to
      counsel correctly or plan appropriate perinatal management. Lung disorders,
      congenital heart disease and chromosomal anomalies will be the principal
      differential diagnoses.

PMID- 12797300
TI  - Trends in sonographic fetal organ visualization.
AB  - In order to assess changes in sonographic visualization over the last 6 years,
      7092 second- and third-trimester ultrasound examinations from separate
      pregnancies in three individual years (1451 in 1985, 3016 in 1988, and 2625 in
      1991) were compared. Overall, visualization across all gestational ages improved
      from 63.9% (1985) to 85.8% (1988) to 87.3% (1991), with the year in which the
      scan was performed explaining 19.6% of the variance in visualization. Maternal
      size (as determined by body mass index) remained the major determinant of
      ultrasound visualization in 1991 (r(2) = 11.2%), with gestational age explaining
      only 5.2% additional variance. Overall organ visualization was maximal at 21-23
      weeks' gestation, with the decline in later gestation primarily accounted for by
      worsened visualization of fetal extremities and spine. Improved fetal
      visualization earlier in the second trimester and the advent of embryonic
      visualization in the first trimester may allow a continuum of prenatal
      sonographic diagnosis.

PMID- 12797301
TI  - Ultrasound screening during pregnancy: psychological strain experienced by the
      investigating staff.
AB  - Ultrasound screening during pregnancy in Sweden is mostly performed by midwives.
      Detection of abnormalities may lead to psychological stress in the pregnant woman
      as well as the sonographer. In order to evaluate the emotional reactions of the
      staff, 95 midwives participated in an inquiry. From the results, it is obvious
      that the midwives experienced strong and overwhelming emotions. There was no
      organization for feedback for 50% of the midwives and 33% did not feel that they
      had enough support.

PMID- 12797302
TI  - First-trimester fetal biometry using transvaginal sonography.
AB  - First-trimester fetal biometry using transvaginal sonography is now feasible and
      desirable due to improved imaging and probe maneuverability. A study of 144 early
      normal pregnancies with precise dates is presented. Regression models were
      constructed for the crown-rump length, biparietal diameter, head circumference
      and abdominal circumference. Error analysis of the technique and calculations was
      performed. First-trimester fetal biometry may be used for obtaining precise
      estimates of gestational age and may help to detect early fetal maldevelopment
      resulting in abnormal growth.

PMID- 12797303
TI  - An investigation of fetal growth using serial ultrasound data.
AB  - Serial ultrasonic measurements were performed in 67 Caucasian fetuses from 20
      weeks' gestation until term to derive reference standards for abdominal
      circumference (AC) and estimated fetal weight (EFW). The variances of both AC and
      EFW increased with gestational age. Four mathematical models (linear, quadratic,
      Gompertz and Rossavik) were fitted to the log(10)(AC) and log(10)(EFW) data from
      each fetus using least squares regression analysis. The standard deviations of
      the residual error were greatest for the linear model. The linear model also
      overestimated the final log(10)(AC) while the linear, Gompertz and Rossavik
      models all overestimated the final log(10)(EFW) when these data were omitted from
      the fitting process. The individual quadratic constants were, therefore, used to
      produce 67 individual growth curves. Values of log(10)(AC) and log(10)(EFW) for
      each fetus at exact gestational ages between 20 and 40 weeks were derived by
      interpolation; the mean and standard deviation values were then used to derive
      centile ranges for abdominal circumference and estimated fetal weight. These
      standards should prove useful in the assessment of fetal growth.

PMID- 12797304
TI  - Effects of maternal hyperoxygenation on ductus venosus flow velocity waveforms in
      normal third-trimester fetuses.
AB  - On the basis of the data obtained in sheep fetuses showing a high interdependence
      between umbilical vein oxygenation and ductus venosus flow, we investigated the
      effect of maternal hyperoxygenation on ductus venosus velocity waveforms in
      normal third-trimester human fetuses. Ductus venosus velocity waveforms were
      recorded by using color and pulsed Doppler ultrasonography before and after 15
      min of maternal administration of humidified 60% oxygen. During maternal
      hyperoxygenation, there was a significant increase of both estimated peak
      velocities during systole, diastole and atrial contraction and the mean temporal
      velocity during the total cardiac cycle and systolic and diastolic portions. On
      the other hand, during maternal hyperoxygenation, no significant changes were
      found in fetal heart rate or in the ratios between peak velocities and mean
      temporal velocities during systole and diastole. These findings suggest a close
      relationship between fetal oxygenation and ductus venosus velocity waveforms that
      may be useful in monitoring fetal hypoxemia.

PMID- 12797305
TI  - Echo patterns of benign cystic teratomas by transvaginal ultrasound.
AB  - The transvaginal ultrasound echo patterns of 39 surgically proven cystic
      teratomas were retrospectively reviewed. Six different ultrasound echo patterns
      could be differentiated, ranging from purely cystic to densely echogenic.
      Importantly, in 82% of the tumors, areas of dense echogenicity were noted.
      Although the transvaginal appearance of cystic teratomas may allow correct
      preoperative prediction, the variable nature of the echo patterns makes
      differentiation from malignant tumors difficult.

PMID- 12797306
TI  - Preoperative ultrasonic assessment of women undergoing gamete intrafallopian
      transfer: a prospective study of 350 cases.
AB  - A total of 350 women due to undergo gamete intrafallopian transfer were scanned
      vaginally on the operation day and the findings were compared with those recorded
      2 days previously when human chorionic gonadotropin was administered. The aim was
      to assess the clinical value of ultrasound assessment on the operation day,
      especially from a prognostic point of view. Seven women (2%) were found to have
      already ovulated and evidence of imminent ovulation was detected in another 27
      cases (7.7%). There were more frequent and more marked increases in the number of
      follicles with a diameter of > 14 mm, in the diameter of the leading follicle and
      in the endometrial thickness in the women who subsequently conceived. The
      endometrial reflectivity was brighter than the myometrium (grade A) in 77.3% of
      the women who conceived, compared with only 37.5% of those who did not conceive.
      These differences were statistically significant. It was concluded that
      follicular and endometrial changes recorded on the day of gamete intrafallopian
      transfer may have a prognostic value, as the pregnancy rate was higher in women
      who had the favorable ultrasonographic features outlined in the study.

PMID- 12797307
TI  - Transvaginal sonography of the uterine cavity with hysteroscopic correlation in
      the investigation of infertility.
AB  - This report describes the correlation of hysteroscopic findings with preoperative
      transvaginal sonography in 200 patients being investigated for infertility. Real
      time ultrasound examination was performed on days 7, 14 and 21 in spontaneous
      ovulatory cycles. Diagnostic hysteroscopy was performed in the subsequent cycle.
      The abnormalities detected using transvaginal sonography were intrauterine
      adhesions, submucous fibroids, endometrial polyps, endometritis and a non
      specific irregular endometrium. A total of 182 patients were diagnosed correctly
      to have an abnormality by transvaginal sonography giving a false-positive rate of
      5.5%. The sensitivity of transvaginal sonography in detecting endometrial
      pathology was 98.9% with a positive predictive value of 94.3%. The positive
      predictive values for specific abnormalities were 98.5% for intrauterine
      adhesions, 91.7% for submucous fibroids, 91.4% for endometrial polyps, 85.7% for
      endometritis and 85.7% for irregular endometrium. These data show a strong
      correlation between findings from transvaginal sonography and hysteroscopy.
      Transvaginal sonography may be used to detect intrauterine pathology and identify
      patients in whom hysteroscopy and hysteroscopic surgery are indicated.

PMID- 12797308
TI  - Excess concepti compared with number of embryos transferred in in vitro
      fertilization.
AB  - To reduce the risk of multiple pregnancy, most in vitro fertilization programs
      limit the number of embryos transferred; because monozygotic twinning may occur,
      it is possible that more concepti are produced than the number of embryos
      transferred. To quantify the prevalence of this phenomenon, 1820 clinical
      pregnancies generated from 11,601 in vitro fertilization treatment cycles were
      reviewed. Two patients conceived four fetuses each after having had three embryos
      transferred, while one conceived three fetuses after having had two embryos
      transferred. The overall prevalence rate was, therefore, one in 607 cases. The
      obstetric details of these three pregnancies are reported.

PMID- 12797309
TI  - Transvaginal color Doppler sonography in the assessment of pelvic tumor
      vascularity.

PMID- 12797310
TI  - Current readings in nuclear medicine.

PMID- 12797312
TI  - Glycoprotein B genotyping of  cytomegalovirus strains isolated in a pediatric
      population.
AB  - To better characterize cytomegalovirus (CMV) isolates in a pediatric population,
      we performed glycoprotein B genotyping of isolates from CMV culture-positive
      patients during a 3-year period at Children's Hospital Medical Center,
      Cincinnati, Ohio. The most common sources for CMV isolation were respiratory and
      urine cultures. Among 61 isolates glycoprotein B genotype distribution was
      genotype 1, 32%; genotype 2, 24%; genotype 3, 32%; and genotype 4, 10%. Among
      viremic isolates there was a trend favoring type 1 genotype (P = 0.057).

PMID- 12797311
TI  - [Problems of schizophrenia discussed at the 11th International Congress on
      Psychophysiology.  July 29-August 3 2002, Montreal, Canada)].

PMID- 12797313
TI  - Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in
      children treated with protease inhibitors.
AB  - We conducted a prospective evaluation for evidence of the HIV-associated
      lipodystrophy syndrome of 26 children infected with HIV-1. Six children had
      evidence of body fat redistribution. Nine children showed laboratory evidence of
      insulin resistance. All children with body fat distribution or insulin resistance
      had been treated with protease inhibitors. Children treated with protease
      inhibitors had higher total cholesterol, higher low density lipoprotein
      cholesterol and higher triglycerides than untreated children.

PMID- 12797314
TI  - Arcanobacterium haemolyticum sinusitis and orbital cellulitis.
AB  - We present a case of sinusitis and orbital cellulitis in a 9-year-old girl caused
      by the Gram-positive bacillus Arcanobacterium haemolyticum. In addition to
      antimicrobial chemotherapy, two surgical procedures were required to drain the
      ethmoid and maxillary sinus cavities and a subperiosteal abscess.

PMID- 12797315
TI  - Cat-scratch disease occurring in three siblings simultaneously.
AB  - We report for the first time three siblings with cat-scratch disease occurring
      simultaneously. Case 1 was an 8-year-old boy with enlarged supraclavicular lymph
      nodes and fever. Case 2 was the 11-year-old sister whose presentation was a
      prolonged febrile illness. Case 3 was a 13-year-old male adolescent with adenitis
      of the neck and thigh. All three patients were treated with rifampin with
      improvement of their symptoms.

PMID- 12797316
TI  - First case of confirmed rotavirus meningoencephalitis in Germany.
AB  - We report the case of a 9-year-old girl in Germany with acute meningoencephalitis
      associated with rotavirus gastrointestinal infection. Sequence analysis revealed
      a genetic relationship of the strain to rotaviruses with subgroup II specificity.
      Reverse transcription-PCR was positive for rotavirus.

PMID- 12797317
TI  - Concurrent infectious mononucleosis and measles: a potentially life-threatening
      association sharing underlying immunodeficiency.
AB  - We report lethal interstitial pneumonia in an 18-year-old young man with measles
      infection following recent infectious mononucleosis. We speculate that the
      documented T cell immune impairment caused by the concurrent Epstein-Barr and
      measles viral infections (as expressed by a proportionately low CD4+ lymphocyte
      count) was responsible for the complicated clinical course and unfavorable
      outcome.

PMID- 12797318
TI  - Combined systemic and intrapleural treatment of Aspergillus pulmonary empyema
      after invasive aspergillosis.
AB  - A 12-year-old immunocompromised boy was hospitalized because of invasive
      aspergillosis with lung and central nervous system involvement. He was treated
      with surgery and liposomal amphotericin B, but he developed a pulmonary empyema
      and a bronchopleural-cutaneous fistula. A catheter was placed through the
      fistula, and amphotericin B (up to 50 mg in 10 ml of 5% dextrose) was instilled
      daily into the pleural cavity for 45 days. Treatment was well-tolerated, and the
      empyema resolved completely, with no evidence of recurrence after 2 years of
      follow-up.

PMID- 12797320
TI  - [Prevent and treatment of the field of internal medicine].

PMID- 12797319
TI  - Recurrent fevers in a five-year-old boy with cystic fibrosis.

PMID- 12797321
TI  - [Major advances in infectious diseases and parasitology in the recent decade in
      China. Writing Group on Infectious Diseases and Parasitology, Editorial Board,
      Chinese Journal of Internal Medicine].

PMID- 12797322
TI  - [Mythology and the medicinal plants of antiquity].
AB  - In any civilization, nature is closely bound to the world of divinities. This is
      clearly seen in the Mediterranean world of Antiquity in every reference to the
      medicinal plants. Our aim, in this study, was to demonstrate the link between
      mythology and medicine. Through several centuries of medicinal practice, appears
      a therapeutic knowledge close to become a science. In spite of many gaps, errors
      and illusions thus emerges a first attempt to master the art of healing. Is it
      possible to speculate on a new type of drug research guided from ancient texts?
      Ethnopharmacology investigating medicinal traditions of the world has already
      obtained in this field some spectacular findings. At the moment, it would be
      difficult to predict the future of archeopharmacology but as Paul Valery said:
      "Present is nothing else than a future nutriment for the past".

PMID- 12797323
TI  - [Advances in endocrinology in the recent decade in China. Writing Group on
      Endocrinology, Editorial Board, Chinese Journal of Internal Medicine].

PMID- 12797325
TI  - [Advances in the prevention and treatment of respiratory diseases in the recent
      years in China].

PMID- 12797324
TI  - [Development of rheumatology in the recent decade in China].

PMID- 12797326
TI  - [A review of cardiovascular studies in the recent decade in China. Writing Group
      on Cardiovascular Diseases, Editorial Board, Chinese Journal of Internal
      Medicine].

PMID- 12797327
TI  - [Major advances in diseases of the digestive system in recent years in China].

PMID- 12797328
TI  - [Recent advances in nephrology in China].

PMID- 12797329
TI  - Medication administration: who's doing what?

PMID- 12797330
TI  - Listen up.

PMID- 12797332
TI  - [Advances in neurology in the recent years in China].

PMID- 12797331
TI  - [Advances in hematology in the recent decade in China].

PMID- 12797333
TI  - Aging skin addendum.

PMID- 12797334
TI  - Can I stop a drug infusion to draw blood?

PMID- 12797335
TI  - Managing your patient's arterial ulcer.

PMID- 12797336
TI  - Introduction: treatment of Gram-positive infections.

PMID- 12797337
TI  - Using an ear thermometer.

PMID- 12797338
TI  - Clarifying a medication order.

PMID- 12797339
TI  - The 50th annual meeting of the Japanese Association for Laboratory Animal
      Science. Saitama, Japan. May 29-31, 2003. Abstracts.

PMID- 12797340
TI  - Efficacy of the topical nasal steroid budesonide on improving sleep and daytime
      somnolence in patients with perennial allergic rhinitis.
AB  - BACKGROUND: Improving quality of life is considered to be a major endpoint and
      motivation for clinical intervention in patients with perennial allergic rhinitis
      (PAR). In addition to classical symptoms of congestion, pruritus, and rhinorrhea,
      patients will often complain of not being able to sleep well at night and of
      feeling fatigued during the day. Like sleep apnea, PAR has also been shown to
      cause sleep disturbance and consequently worsen daytime fatigue and somnolence.
      HYPOTHESIS: It is proposed that by decreasing nasal obstruction due to allergic
      rhinitis by treating with the topical steroid budesonide, symptoms of daytime
      fatigue and somnolence can be improved. METHODS: Twenty-two subjects were
      enrolled in a double-blind, placebo-controlled, crossover study using Baalam's
      design. Patients were treated with either budesonide 128 g/day or placebo.
      Subjective data include the Epworth Sleepiness Scale, Functional Outcomes of
      Sleep Questionnaire, Rhino-conjunctivitis Quality of Life Questionnaire, and a
      daily diary recording nasal symptoms, sleep problems, and daytime fatigue.
      RESULTS: The results illustrated that the topical nasal corticosteroid
      significantly improved daytime fatigue (P = 0.03), somnolence (P = 0.02), and
      quality of sleep (P = 0.05) compared to placebo in patients suffering from PAR.
      SUMMARY: Budesonide is able to improve congestion, sleep, and daytime somnolence.

PMID- 12797341
TI  - Helping patients with dysphagia eat.

PMID- 12797342
TI  - Myths & facts...about nosocomial pneumonia.

PMID- 12797343
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan.  2002.
      Abstracts].

PMID- 12797344
TI  - Predicting heart disease with C-reactive protein.

PMID- 12797345
TI  - Bacillus anthracis.

PMID- 12797346
TI  - Conversations with Frederic d'Allest. Interview by Theo Pirard.

PMID- 12797347
TI  - [Brachial flow-mediated dilation: measurement and clinical implications].

PMID- 12797348
TI  - [Meeting the challenge of beta-lactamases].

PMID- 12797349
TI  - Crohn's disease and IL-10 therapy: promise regained.

PMID- 12797350
TI  - O brother, where art thou? The case for siblings, environment, and inflammatory
      bowel disease.

PMID- 12797351
TI  - Dexamethasone pulse steroids in ulcerative colitis--is it time for a change?

PMID- 12797352
TI  - A Crohn's repertoire: T cell receptor gammadelta.

PMID- 12797354
TI  - Bibliography. Current world literature. Urolithiasis.

PMID- 12797353
TI  - Bibliography. Current world literature. Endoscopic and laparoscopic surgery.

PMID- 12797355
TI  - [Smoking and chronic obstructive pulmonary disease].

PMID- 12797356
TI  - [Discussing the choice of controls prevention and treatment].

PMID- 12797357
TI  - The ALLHAT and the cardioprotection conferred by diuretics in hypertensive
      patients: a connection with uric acid?

PMID- 12797358
TI  - [The arterial system of the Japanese anatomist Buntaro Adachi].
AB  - The Japanese anatomist Buntaro Adachi (1865-1945) has to be regarded as the
      pivotal figure of vascular anatomy of all times. His masterpiece, "Das
      Arteriensystem der Japaner" was published in 1928 as a result of over thirty
      years of research on hundreds of bodies, and it remains today a bibliographical
      reference that can't be ignored. However, Buntaro Adachi intended writing much
      more than an encyclopedia of vascular anatomy : he wanted to introduce a concept
      of racial anatomy, pointing out the anatomical specificities in Japanese people,
      probably in reaction against the Chinese and then Occidental influence on
      anatomical knowledge in Japan.

PMID- 12797359
TI  - Pretreatments with a novel pure potassium channel blocker, Nifekalant, were
      effective in the electrical atrial defibrillation: a report of two cases.

PMID- 12797361
TI  - [Pay more attention to the study of the treatment of hepatitis B].

PMID- 12797362
TI  - [Heterogenity and immunoassay of specificity insulin in blood].

PMID- 12797360
TI  - [The new terms of "infectious diseases": the birth of the clinical bacteriology
      and infectious pathology in France].
AB  - The terms of "infectious diseases" appeared for the first time in Charles
      Bouchard's classification at the beginning of the twentieth century. Louis
      Pasteur's role was significant in the birth of a new pathology but the common
      physicians had to assume the conception of a new branch of medicine. Alain
      Contrepois describes the moving of French medicine from 1870 to 1914, outside the
      German bacteriology whose knowledge remained misunderstood owing to the political
      circumstances.

PMID- 12797364
TI  - Bibliography: current world literature.

PMID- 12797363
TI  - [Sarcopenia--is infirmity in old age avoidable?].

PMID- 12797365
TI  - Antihypertensive treatment and the kidney.

PMID- 12797366
TI  - A locum adventure.

PMID- 12797367
TI  - An overview of health care spending patterns in the United States: using national
      data sources to explore trends in nursing services.

PMID- 12797368
TI  - "The nursing shortage".

PMID- 12797369
TI  - The nursing shortage.

PMID- 12797370
TI  - The 1965 entry into practice proposal--is it relevant today?

PMID- 12797371
TI  - Efficacy of a larger version of the hybrid artificial liver support system using
      a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure
      pig model for preclinical experiments.
AB  - We have reported the usefulness of a polyurethane foam packed-bed culture system
      of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS).
      The aim of this study was to evaluate in detail the efficacy in serum parameters
      regarding the liver function of a larger version of the PUF-HALSS containing 2 x
      10(10) porcine hepatocytes for clinical use in warm ischemic liver failure pigs.
      Warm ischemic liver failure pigs weighing 25 kg were divided into two groups: (1)
      a control group (n = 3), in which each pig was attached to a PUF-HALSS without
      hepatocytes, and (2) a HALSS group (n = 3), in which each pig was attached to a
      PUF-HALSS. In the HALSS group, the increase of blood ammonia was completely
      suppressed and blood lactate levels were significantly suppressed. The Fisher's
      ratio was better maintained, and the increase of total bile acid,
      glycochenodeoxycholic acid, and taurochenodeoxycholic acid was significantly
      suppressed in the HALSS group. Serum creatinine levels were significantly lower,
      and blood glucose levels were significantly higher in the HALSS group. Serum
      levels of tumor necrosis factor- a were not elevated in either group. In
      conclusion, the larger version of the PUF-HALSS demonstrated many advantages as a
      liver support system in warm ischemic liver failure pigs.

PMID- 12797372
TI  - Apoptotic cell death and function of cryopreserved porcine hepatocytes in a
      bioartificial liver.
AB  - We have previously shown that cryopreservation leads to increased apoptotic death
      of porcine hepatocytes intended for use in a bioartificial liver (BAL). This
      study was designed to determine if a broad-spectrum caspase inhibitor, IDN-1965,
      reduced apoptosis and increased function of cryopreserved porcine hepatocytes in
      static culture or in a BAL. Porcine hepatocytes were studied immediately after
      isolation and after 2 weeks of cryopreservation in liquid nitrogen using medium
      supplemented with 25 micromol/L IDN-1965 or vehicle. Both apoptotic and necrotic
      cells were observed in cultures of fresh and cryopreserved hepatocytes, but the
      percentage of apoptotic cells increased after cryopreservation. Cryopreservation
      in IDN-1965 improved hepatocyte viability and reduced apoptotic cell death
      determined by TUNEL assay. Cryopreservation of hepatocytes in IDN-1965 was also
      associated with reduced caspase 3-like activity, decreased release of cytochrome
      c from mitochondria, and a slower decline in mitochondrial membrane potential
      after thawing. These markers of apoptosis were lowest after cryopreservation when
      IDN-1965 was added to both the culture and cryopreservation medium. Functional
      markers of hepatocyte activity (albumin production, diazepam metabolism, urea
      production) were also increased after cryopreservation and culture of hepatocytes
      in medium supplemented with 25 micromol/L IDN-1965. Cryopreservation of porcine
      hepatocytes in the presence of caspase inhibitor IDN-1965 was associated with
      reduced apoptosis and improved function of porcine hepatocytes in both static
      culture and a perfused BAL. These data demonstrate that inhibition of apoptosis
      also preserves cell function.

PMID- 12797373
TI  - Dynamics of cryoprotectant permeation in porcine heart valve leaflets.
AB  - Valve replacement is a common cardiovascular procedure for the treatment of a
      variety of congenital and acquired defects. Many surgical programs rely on
      cryopreserved heart valves from regional tissue bank programs to meet clinical
      demands. Current cryopreservation strategies for heart valves are empirically
      derived. The aim of this study was to use proton nuclear magnetic resonance
      spectroscopy (NMR) to monitor changes in cryoprotectant concentration in isolated
      heart valve leaflets. Porcine aortic valves were locally obtained, freshly
      isolated, and allowed to equilibrate at various experimental temperatures (22
      degrees C, 10 degrees C, 4 degrees C) for 1 h prior to immersion in 1 M Me2SO
      solution. At defined intervals (0, 0.25, 0.5, 1, 2, 6, and 24 h) the valves were
      removed from the Me2SO and the leaflets were rapidly dissected and equilibrated
      in deuterium oxide (D2O). Using previously described techniques the Me2SO
      concentration in the heart valve leaflets was determined by NMR and the diffusion
      coefficient was calculated as a function of time and temperature. Heart valve
      leaflets were fully equilibrated with Me2SO after approximately 2 h of exposure
      at 22 degrees C while equilibrium was not reached >6 h or more at 10 degrees C
      and 4 degrees C. These results indicate that that permeation of Me2SO in heart
      valves is strongly temperature dependent Furthermore, this study provides a
      quantitative measure of Me2SO permeation and cryoprotectant at equilibration in
      heart valve leaflets. The clinical applications of these findings may help to
      optimize the balance between the protective and toxic effects of cryoprotectants
      and lead to improved methods of preservation of heart valves.

PMID- 12797374
TI  - Digital imaging as a possible approach in evaluation of islet yield.
AB  - Digital image analysis (DIA) is a new method in assessment of islet amount, which
      is expected to provide reliable and consistent results. We compared this method
      with conventional counting of small numbers of rat islets. Islets were isolated
      from 8 pancreases and counted in 24 samples in duplicate, first routinely by
      sizing according to estimated diameters under a calibrated reticule and then by
      processing of islets pictures taken by camera. As presumed, no significant
      difference was found in absolute numbers of islets per sample between DIA and
      conventional assessment. Volumes of islets per sample measured by DIA were on
      average more than 10% higher than amounts evaluated conventionally, which was
      statistically significant. DIA has been shown to be an important method to remove
      operator bias and provide consistent results. Evaluation of only two dimensions
      of three-dimensional objects still represents a certain limitation of this
      technique. With lowering of computer prices the system could become easily
      available for islet laboratories.

PMID- 12797375
TI  - Neural differentiation and incorporation of bone marrow-derived multipotent adult
      progenitor cells after single cell transplantation into blastocyst stage mouse
      embryos.
AB  - Previously we reported the characterization of multipotent adult progenitor cells
      (MAPCs) isolated from the bone marrow of rodents. In that study, single murine
      MAPCs derived from ROSA-26, beta-galactosidase (beta-Gal)-positive transgenic
      mice were injected into E3.5 C57/B16 mouse blastocysts. The resultant chimeric
      blastocysts were then implanted into pseudopregnant females and were allowed to
      develop naturally through birth and into adulthood. Chimeric mice were sacrificed
      6 to 20 weeks after birth, and were processed for histological analysis. Beta
      galactosidase activity was identified in all organs and tissues examined, and
      tissue-specific differentiation and engraftment was confirmed by colabeling with
      antibodies that recognize beta-Gal and tissue-specific markers. In the present
      study we have examined neural engraftment derived from the clonal expansion of a
      single MAPC during rodent development, and characterized the neural phenotype of
      MAPCs in the resultant chimeric animals. Donor cell-derived beta-Gal activity was
      evident throughout the brain. Double and triple immunofluorescent labeling
      studies revealed MAPC-derived neurons (NeuN/beta-Gal) and astrocytes (GFAP/beta
      Gal) in the cortex, striatum, medial septal nucleus, hippocampus, cerebellum,
      substantia nigra, and thalamus. More specifically, donor-derived neurons
      contributed to each of the cellular layers of the cortex; the pyramidal and
      granule cell layers, as well as the hilus, of the hippocampus; Purkinje and
      granule cell layers in the cerebellum; and GABAergic cells in the caudate and
      putamen. This study characterizes the potential for MAPCs to differentiate into
      specific neuronal and glial phenotypes, and to integrate normally during
      development, after implantation into blastocysts, and provides additional
      evidence that MAPCs exhibit properties similar to embryonic stem cells.

PMID- 12797376
TI  - The effects of various concentrations of FGF-2 on the proliferation and neuronal
      yield of murine embryonic neural precursor cells in vitro.
AB  - Embryonic neural precursors (ENPs), also termed neural stem cells or
      "neurospheres," are an attractive potential source of tissue for neural
      transplantation, because of their capacity to expand in number in vitro while
      retaining the ability to develop into the major phenotypes of the CNS. ENPs are
      isolated from the developing brain and proliferate in the presence of mitogens
      such as FGF-2 and EGF. Subsequent withdrawal of these mitogens and exposure to a
      suitable substrate results in differentiation into the major cell types of the
      CNS. As well as its role in precursor cell expansion, FGF-2 also plays a key role
      in the division of astrocytes, and in neuronal differentiation. Thus, it is
      important to establish the optimal concentrations of this factor for expansion
      and differentiation of neuronal phenotypes. Here we explore the effect of FGF-2
      concentrations ranging from 1 to 20 ng/ml on the expansion and differentiation
      capacity of ENPs isolated from the cortex and striatum of E14 mice. ENP expansion
      was seen under all conditions, but was greatest at 10 and 20 ng/ml and least at 1
      ng/ml. The numbers of neurons (as a proportion of total cell number)
      differentiating from these ENP populations appeared to be greatest at 1 ng/ml.
      However, once adjustments were made for the amount of expansion at each dose,
      final neuronal yield was maximum at the highest concentration of FGF-2 used (20
      ng/ml).

PMID- 12797377
TI  - Melatonin-secreting pineal gland: a novel tissue source for neural
      transplantation therapy in stroke.
AB  - Chronic systemic melatonin treatment attenuates abnormalities produced by
      occlusion of middle cerebral artery (MCA) in adult rats. Because the pineal gland
      secretes high levels of melatonin, we examined in the present study whether
      transplantation of pineal gland exerted similar protective effects in MCA
      occluded adult rats. Animals underwent same-day MCA occlusion and either
      intrastriatal transplantation of pineal gland (harvested from 2-month-old rats)
      or vehicle infusion. Behavioral tests (from day of surgery to 3 days
      posttransplantation) revealed that transplanted stroke rats displayed
      significantly less motor asymmetrical behaviors than vehicle-infused stroke rats.
      Histological analysis at 3 days posttransplantation revealed that transplanted
      stroke rats had significantly smaller cerebral infarction than vehicle-infused
      rats. Additional experiments showed that pinealectomy affected transplantation
      outcome, in that transplantation of pineal gland only protected against stroke
      induced deficits in stroke animals with intact pineal gland, but not in
      pinealectomized stroke rats. Interestingly, nonpinealectomized vehicle-infused
      stroke rats, as well as pinealectomized transplanted stroke rats, had
      significantly lower melatonin levels in the cerebrospinal fluid than
      nonpinealectomized transplanted stroke rats. We conclude that intracerebral
      transplantation of pineal gland, in the presence of host intact pineal gland,
      protected against stroke, possibly through secretion of melatonin.

PMID- 12797378
TI  - Ultrastructural characterization of dissociated embryonic ventral mesencephalic
      tissue treated with neuroprotectants.
AB  - Poor survival and differentiation of grafted dopamine neurons limits the
      application of clinical transplantation in Parkinson's disease. The survival of
      grafted dopamine neurons is only improved by a factor of 2-3 by adding
      neuroprotectants during tissue preparation. We used dye exclusion cell viability
      and electron microscopy to investigate the effects of the caspase inhibitor ac
      YVAD-cmk and the lazaroid tirilazad mesylate on ultrastructural changes in
      dissociated embryonic mesencephalic cells. In addition, we examined whether the
      neuroprotectants selectively counteracted specific signs of neurodegeneration.
      Cell viability decreased significantly over time in both control and treated cell
      suspensions, but the number of viable cells remaining was significantly higher in
      tirilazad mesylate-treated cell suspensions. In control samples, the proportion
      of cells with an ultrastructure consistent with healthy cells decreased from 70%,
      immediately after dissociation, to 30% after 8 h of incubation. Similar changes
      were also observed in cell suspensions treated with neuroprotectants. Thus, the
      neuroprotectants examined did not block the development of specific morphological
      signs of neurodegeneration. However, when also taking into account that dead
      cells lysed and disappeared from each cell suspension with time, we found that
      the total number of remaining viable cells with healthy nuclear chromatin or
      intact membrane integrity was significantly higher in the tirilazad mesylate
      treated group. The results indicate that tirilazad mesylate protects only a small
      subpopulation of embryonic mesencephalic cells from degeneration induced by
      mechanical trauma during tissue dissection and dissociation.

PMID- 12797379
TI  - Fetal lateral ganglionic eminence attracts one of two morphologically different
      types of tyrosine hydroxylase-positive nerve fibers formed by cultured ventral
      mesencephalon.
AB  - The purpose of this study was to investigate the influence of fetal lateral
      ganglionic eminence (LGE) on nerve fiber outgrowth formed by fetal ventral
      mesencephalon (VM). Organotypic tissue cultures of fetal VM and LGE plated as
      single or cocultures were employed. Survival time was 3-21 days in vitro. Nerve
      fiber outgrowth and migration of astrocytes were analyzed using
      immunohistochemistry for tyrosine hydroxylase (TH) and S100. In addition,
      cultures were labeled with the TUNEL technique and with antibodies directed
      against neurofilament (NF) in order to study apoptosis and retraction of nerve
      fibers, respectively. The results revealed two morphologically different types of
      TH-positive outgrowth growing into the substrate. The initially formed TH
      positive outgrowth radiated continuously without changing direction, while a
      second wave of TH-positive outgrowth became obvious when the initial growth
      already had reached a distance of approximately 1000 microm. The second wave of
      TH-positive outgrowth radiated from the tissue, but at a certain distance changed
      direction and formed a network surrounding the culture. The initially formed TH
      positive growth was not associated with the presence of S100-positive astrocytes
      and avoided to grow into the LGE. At longer time points the first wave of TH
      positive nerve fibers appeared dotted, with disrupted NF-immunoreactive fibers
      and in most cultures these long distance growing fibers had disappeared at 21
      days in vitro. The second wave of TH-positive nerve fibers was growing onto a
      layer of glia and never reached the distance of the first wave. LGE became
      innervated by TH-positive fibers at the time point for when the second wave of TH
      positive growth had been initiated, and the innervation appeared in TH-dense
      patches that also showed a high density of S100-positive astrocytes.
      Significantly increased TUNEL activity within LGE portion of cocultures was
      observed when TH-positive fibers entered the LGE and formed patches. In
      conclusion, two morphologically different types of TH-positive outgrowth were
      found and the initially formed fibers neither targeted the LGE nor were they
      guided by glial cells, but their potential to grow for long distances was high.

PMID- 12797380
TI  - The role of pretraining on skilled forelimb use in an animal model of
      Huntington's disease.
AB  - After a unilateral striatal lesion, animals have generally been seen to have a
      bilateral impairment in paw reaching, with the contralateral paw being more
      affected. However, most studies to date have not used a pretraining paradigm to
      assess maximal capacity for paw reaching, to compare with any lesion-induced
      loss. This study compared animals that were pretrained with naive animals in
      their ability to paw reach after a striatal lesion, to address the role of the
      striatum in either acquisition or execution of this motor task. All lesioned
      animals showed a significant decrease in reaching ability with their
      contralateral paw compared with the ipsilateral paw. Pretrained lesioned animals
      showed a clear lesion deficit with the contralateral paw immediately after
      lesion, and no impairment whatsoever with the ipsilateral paw. Naive lesioned
      animals showed delayed acquisition of the task with both paws, possibly due to
      postural deficits, and a lasting deficit on the contralateral side. The
      variability of performance between animals was higher in the naive lesioned
      group. These results suggest that animals should be pretrained on the staircase
      task prior to lesion to enable maximum sensitivity in detecting both loss and
      recovery of function of skilled forelimb use.

PMID- 12797381
TI  - Axonal regeneration across long gaps in silicone chambers filled with Schwann
      cells overexpressing high molecular weight FGF-2.
AB  - Basic fibroblast growth factor (FGF-2) has been shown to enhance the survival and
      neurite extension of various types of neurons including spinal ganglion neurons.
      In addition, endogenous FGF-2 and FGF receptors are upregulated following
      peripheral nerve lesion in ganglia and at the lesion site. FGF-2 protein is
      expressed in different isoforms (18 kDa, 21 kDa, 23 kDa) and differentially
      regulated after nerve injury. In the rat we analyzed the regenerative capacity of
      the high molecular weight (HMW) FGF-2 isoforms (21/23 kDa) to support the
      regeneration of the axotomized adult sciatic nerve across long gaps. The nerve
      stumps were inserted into the opposite ends of a silicone chamber resulting in an
      interstump gap of 15 mm. Silicone tubes were filled with Matrigel or a mixture of
      Schwann cells (SC) and Matrigel. SC were prepared from newborn rats and
      transfected to overexpress HMW FGF-2. Four weeks after the operation procedure,
      channels were analyzed with regard to tissue cables bridging both nerve stumps
      and myelinated axons distal to the original proximal nerve stump. Peripheral
      nerves interposed with HMW Schwann cells displayed significantly enhanced nerve
      regeneration, with the greatest number of tissue cables containing myelinated
      axons and the highest number of myelinated axons. These results suggest that a
      cellular substrate together with a source of a trophic factor could be a
      promising tool to promote nerve regeneration and, therefore, become useful also
      for a clinical approach to repair long gaps.

PMID- 12797382
TI  - Transection of the adult rat spinal cord upregulates EphB3 receptor and ligand
      expression.
AB  - Eph receptors and ligands represent two families of proteins that control axonal
      guidance during development. Recent work has shown that several Eph receptors are
      expressed postnatally. Because the Eph molecules represent a class of axon
      guidance molecules that are mainly inhibitory to axonal growth, we investigated
      whether EphB3 expression was upregulated in both spinal cord and four supraspinal
      nuclei (locus coeruleus, vestibular, raphe pallidus, and red) 1 week after a
      complete spinal cord thoracic transection. Injured rats had a significant
      increase in EphB3 mRNA and protein expression in the spinal cord. The increased
      EphB3 expression was colocalized with GFAP staining and indicated that astrocytes
      play a role in EphB3 expression after spinal cord injury. No change in EphB3
      expression was seen in supraspinal brain nuclei, which further demonstrated that
      changes in expression were due to changes in the local microenvironment at the
      injury site. The expression of EphB3 was colocalized to regions of the CNS that
      had a high level of EphB3 binding ligands. These data indicate upregulation of
      EphB3 expression after injury may also contribute to an environment in the spinal
      cord that is inhibitory to axonal regeneration.

PMID- 12797384
TI  - Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae
      isolated in four southern European countries (ARISE project) from adult patients:
      results from the cefditoren surveillance program.
AB  - From four southern European countries (Spain, Italy, Portugal, and Greece) 877
      Streptococcus pneumoniae isolates were recovered from adult patients with
      respiratory tract infections between September 2000 and March 2001. The
      antimicrobial susceptibility to 11 antibiotics was determined in a central
      laboratory. Penicillin resistance was high in Greece (47.1%) and Spain (25.1%)
      but much lower in Portugal (7.9%) and Italy (4.8%). On the other hand,
      erythromycin resistance was high in Italy (38.5%) and Spain (36.2%) with no
      statistical difference with Greece (29.4%) but reaching significance (p <0.01)
      with Portugal (15.7%). Resistance to levofloxacin was low (1.5%) but present in
      Spanish and Italian isolates. Cefditoren, a new cephem antibiotic tested, was the
      most potent compound (MIC90 = 0.5 microg/ml) followed by levofloxacin and
      cefotaxime (MIC90 = 1 microg/ml). Given the high rates of penicillin and
      macrolide resistance reported, there is an evident need for new drugs and
      continued antimicrobial surveillance of S. pneumoniae.

PMID- 12797385
TI  - Comparative in vitro activity of PH-027 versus linezolid and other anti-anaerobic
      antimicrobials against clinical isolates of Clostridium difficile and other
      anaerobic bacteria.
AB  - PH-027 is a new 5-triazole oxazolidinone synthesized in our laboratories, which
      shows strong activity against gram-positive aerobic bacteria including clinical
      isolates. The objective of this study was to investigate the in vitro activity of
      this compound in comparison with linezolid and other antibiotics against gram
      positive and gram-negative anaerobes. The in vitro activity of PH-027 in
      comparison with those of linezolid and other antimicrobial agents was evaluated
      against 201 clinical isolates of gram-positive and gram-negative anaerobic
      bacteria by agar dilution and Etest methods. PH-027 showed excellent activity,
      with minimum inhibitory concentrations (MIC) in the range of 0.12-4.0 microg/ml
      against all isolates; MIC90s being 4.0, 1.0, 2.0, 2.0 and 2.0 microg/ml against
      Clostridium difficile, Peptostreptococcus spp., Bacteroides fragilis, Prevotella
      bivia and Fusobacterium spp. respectively. In comparison, linezolid had MIC in
      the range of 0.5-4.0 microg/ml against all isolates, with MIC90s of 2.0, 4.0,
      4.0, 4.0 and 2.0 microg/ml against the same set of bacteria respectively. PH-027
      demonstrated excellent in vitro activity that is superior to linezolid against
      Peptostreptococcus spp., B. fragilis and P. bivia. However, against C. difficile
      and Fusobacterium spp, PH-027 and linezolid showed comparable in vitro activity.
      Against all anaerobes, metronidazole, PH-027 and, to a lesser extent, linezolid
      had the most potent activity. From the results of in vitro susceptibility
      testing, both linezolid and PH-027 show promise in the treatment of anaerobic
      infections.

PMID- 12797383
TI  - The noradrenergic system of aged GDNF heterozygous mice.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for
      noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased
      function of the LC-NE neurons has been found during normal aging and in
      neurodegenerative disorders. We have previously shown that GDNF participates in
      the differentiation of LC-NE neurons during development. However, the continued
      role of GDNF for LC-NE neurons during maturation and aging has not been
      addressed. We examined alterations in aged mice that were heterozygous for the
      GDNF gene (Gdnf+/-). Wild-type (Gdnf+/+) and Gdnf+/- mice (18 months old) were
      tested for locomotor activity and brain tissues were collected for measuring
      norepinephrine levels and uptake, as well as for morphological analysis.
      Spontaneous locomotion was reduced in Gdnf+/- mice in comparison with Gdnf+/+
      mice. The reduced locomotor activity of Gdnf+/- mice was accompanied by
      reductions in NE transporter activity in the cerebellum and brain stem as well as
      decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH)
      immunostaining demonstrated morphological alterations of LC-NE cell bodies and
      abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of
      Gdnf+/- mice. These findings suggest that the LC-NE system of Gdnf+/- mice is
      impaired and suggest that GDNF plays an important role in continued maintenance
      of this neuronal system throughout life.

PMID- 12797386
TI  - Comparative bactericidal activity of fluoroquinolones against clinical isolates
      resistant to fluoroquinolones.
AB  - The bactericidal activity of levofloxacin, ciprofloxacin, moxifloxacin and
      norfloxacin against clinical isolates conventionally classified as resistant to
      fluoroquinolones were compared at their maximum concentrations in serum, urine
      (except moxifloxacin) and bronchial mucosa (except norfloxacin). Time killing
      curves against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis,
      Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus pneumoniae
      were performed. Serum concentrations of the tested drugs were not able to produce
      a bactericidal effect on fluoroquinolone-resistant strains. In the urine series,
      levofloxacin was always bactericidal (decrease > or = 3 logs CFU/ml), while
      norfloxacin and ciprofloxacin were bactericidal on E. coli (both), P. mirabilis
      (norfloxacin) and P. aeruginosa (ciprofloxacin). In the bronchial mucosa series,
      S. pneumoniae was rapidly killed by levofloxacin and moxifloxacin, and K.
      pneumoniae by levofloxacin after 12 hours. In conclusion, the maximum
      levofloxacin concentrations achievable at certain body sites allowed killing even
      of strains defined as resistant by conventional breakpoints.

PMID- 12797387
TI  - Flucytosine and cryptococcosis: which in vitro test is the best predictor of
      outcome?
AB  - The combination of flucytosine and amphotericin B is first choice treatment for
      active cryptococcosis. Because of innate or acquired resistance of Cryptococcus
      neoformans to flucytosine, in vitro testing is mandatory. Yeast nitrogen base
      (YNB) at pH 7.0 is the recommended medium for the broth microdilution test (NCCLS
      M27-A) and for the E-test. In order to verify if minimum inhibitory
      concentrations (MICs) were able to predict treatment outcome, the susceptibility
      of 24 isolates from 21 patients treated with flucytosine alone or in combination
      was tested by the broth microdilution, agar dilution and E-test using YNB either
      at pH 7.0 or at pH 5.4. Only those MICs obtained on YNB pH 5.4 proved to
      correlate with treatment outcome. The present study suggests that in vitro
      susceptibility to flucytosine of C. neoformans isolates should be evaluated on
      YNB pH 5.4 and the test should be standardized accordingly.

PMID- 12797389
TI  - Diffusion of cefepime into cancellous and cortical bone tissue.
AB  - The degree of penetration of an antibiotic into the infection site is an
      important factor in its therapeutic efficacy, particularly in bone and joint
      infections. In the present study, we examined the bone tissue penetration of
      cefepime at a dose of 2 g, and the results were correlated to microbiological
      data to estimate the clinical efficacy of cefepime in bone infections. In this
      open-label, single-arm, noncomparative study, subjects of similar age, body
      weight, height and creatinine clearance who were undergoing elective total hip
      replacement received a single, parenteral 2 g dose of cefepime. Plasma samples
      were collected simultaneously with bone tissue samples 1.5 hours later, on
      average, and analyzed by a validated high performance liquid chromatography
      assay. Ten patients (7 women and 3 men; mean age, 78 years; mean body weight, 57
      Kg; mean creatinine clearance, 56 mL/min) were enrolled. The mean +/- SD plasma
      concentration of cefepime at the time of bone removal was 72.9 +/- 24.4
      microg/mL. The mean +/- SD cefepime concentrations were 73.5 +/- 16.2 microg/mL
      in cancellous bone tissue and 67.7 +/- 17.0 microg/mL in cortical bone tissue.
      The mean +/- SD ratios of cefepime concentration in bone and plasma (bone/plasma)
      were 1.06 +/- 0.23 for cancellous bone tissue and 0.87 +/- 0.37 for cortical bone
      tissue. Cefepime exhibits an excellent diffusion into bone tissue, with
      concentrations achieved in both cancellous and cortical bone tissue greater than
      the minimum concentrations required to inhibit the growth of 90% of strains
      (MIC90) of most of the susceptible pathogens commonly involved in bone
      infections.

PMID- 12797388
TI  - Antiendotoxin activity of antimicrobial peptides and glycopeptides.
AB  - An animal study was performed to investigate the efficacy of two glycopeptides
      and two cationic peptides in the prevention of lethality in a septic shock rat
      model. Adult Wistar rats were given an intraperitoneal injection of 2x10(10) CFU
      of Escherichia coli ATCC 25922, with the exception of an uninfected control group
      (C0). Animals were randomized to receive, immediately after bacterial challenge,
      intraperitoneally isotonic sodium chloride solution (control group C1), 3 mg/Kg
      teicoplanin (group 1), 7 mg/Kg vancomycin (group 2), 1 mg/Kg colistin (group 3),
      1 mg/Kg buforin II (group 4), or 60 mg/Kg piperacillin (group C(PIP)). In
      addition, four groups (1a, 2a, 3a, and 4a) received the above mentioned drugs in
      combination with piperacillin. All compounds and combinations significantly
      reduced the lethality and the number of E. coli in abdominal fluid compared with
      C1 group, with the exception of the glycopeptides. Colistin and buforin II
      combined with piperacillin significantly decreased the lethality compared with
      piperacillin alone. Finally, colistin, buforin II, and teicoplanin significantly
      reduced plasma endotoxin concentration in comparison with piperacillin and saline
      treatment. Antimicrobial peptides and teicoplanin act as antiendotoxin agents and
      enhance the efficacy of piperacillin.

PMID- 12797390
TI  - Ceftriaxone (1 g intravenously) penetration into abdominal tissues when
      administered as antibiotic prophylaxis during nephrectomy.
AB  - A pharmacokinetics study was conducted to determine the effects of ceftriaxone
      administered before nephrectomy on the occurrence of postoperative wound
      infection. Ceftriaxone was administered as antibiotic prophylaxis in 11
      consecutive patients undergoing nephrectomy who received 1,000 mg intravenously
      30 min before surgery. Simultaneous blood and tissue samples were collected at
      three stages of the surgical procedure: opening of the abdominal cavity,
      nephrectomy, and closure of the abdominal cavity. Samples of following tissues
      were assayed: abdominal-wall fat, perirenal fat, kidney cortex and medulla, and
      urine. During the different stages of surgical procedures, ceftriaxone
      concentrations remained higher than the MIC90 of the potential pathogens
      (Staphylococcus aureus, Escherichia coli, and Enterobacteriaceae). In selected
      patients undergoing nephrectomy and requiring antimicrobial prophylaxis such as
      malnourished, debilitated, diabetic or immunosuppressed patients, the use of a
      single dose of ceftriaxone (1,000 mg) makes it possible to offer an optimal
      bacterial coverage for the prevention of postoperative infection. According to
      our kinetic evaluation, ceftriaxone is potentially a good antibiotic for
      prophylaxis in urological surgery.

PMID- 12797391
TI  - Acid tolerance and fecal recovery following oral administration of Saccharomyces
      cerevisiae.
AB  - Probiotic microorganisms to be used as biotherapeutic agents have to resist the
      rigors of the upper human gastrointestinal tract. In this study we evaluated the
      acid tolerance in vitro and the fecal recovery in vivo after oral administration
      of a Saccharomyces cerevisiae strain to healthy volunteers. At the lowest pH
      value (pH 1.0) the yeast load in tablets decreased slightly. From pH 1.0 to pH
      7.0 the release of S. cerevisiae in buffer solutions increased. The selected
      yeast strain showed good tolerance to low pH which mimic the gastric environment.
      After one month of treatment at a dose of 100 million cells per day, S.
      cerevisiae grew from the feces of 6 (37.5%) of the 16 healthy, treated
      volunteers. Based on the results of the present experiments the yeast studied can
      be considered a strain that tolerates adverse conditions comparable to those of
      the human gastrointestinal tract, and when administered orally may colonize the
      bowel of healthy volunteers and even replace resident Candida species.

PMID- 12797392
TI  - Prevalence of Brucella antibodies after acute brucellosis.
AB  - Diagnosis of brucellosis is made by a demonstration of high brucella
      agglutination titer using the Standard Tube Agglutination Test (SAT) in the
      presence of compatible clinical symptoms. In an endemic area like Saudi Arabia,
      persistence of brucella antibodies after recovery from acute brucellosis is not
      uncommon. The aim of this study was to monitor brucella antibody titers after
      successful treatment and clinical cure, and identify factors influencing their
      persistence. Patients clinically cured of acute brucellosis, who have at least
      three serological follow-ups, were reviewed retrospectively. A titer of less than
      1:320 was considered a "serological cure". One hundred sixteen (116) patients
      clinically cured of acute brucellosis were followed up for different lengths of
      time. All patients had no re-infection or relapse at the end of follow-up. The
      actuarial life-table analysis showed an increase in proportion of serologically
      cured from 8.3% in the first three months to 71.4% after two years or more, and
      the median time for serological cure was 18.5 months (SD = 3 months). In
      univariate analysis, older age, male gender, and patients treated with less than
      three antibiotics are more likely to have persistent brucella antibodies of > or
      = 1:320 (P>0.2). The use of doxycycline in the treatment was associated with
      serological cure (51.1% vs. 27.5%) (P<0.05). However, with the Cox regression
      model none of the variables were statistically significant as a prognostic factor
      for serological cure (P>.05). In conclusion, brucella antibodies of 1:320 or
      higher can persist for more than 2 years after successful treatment and clinical
      cure. Re-evaluation of diagnostic titer of brucellosis is required in brucella
      endemic countries.

PMID- 12797393
TI  - Antibiotic lock-technique for the treatment of catheter-related bloodstream
      infections.
AB  - The management of central venous catheter-related bloodstream infections (CRBSI),
      though still debated, requires the removal of the line in most cases: we
      investigated the efficacy of an alternative approach, based on higher
      concentrations of antibiotics locked within the catheter lumen, in an open, pilot
      study aimed at preserving the line in place and at eradicating the infection.
      Thirty consecutive patients carrying a central line over 10 days and who
      fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter
      "locked" with antimicrobials therein; all patients also received systemic
      antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent
      locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%)
      patients retained the catheter in place, appearing to be cleared of infection and
      no treatment-related untoward events were observed. Locks should be considered as
      effective as line removal in the management of bacterial CRBSI in unselected
      patients, and could thus provide advantages in terms of resource sparing and
      lowered antibiotic pressure in the hospital setting.

PMID- 12797394
TI  - Oral antibiotic prophylaxis can influence the inflammatory response in aortic
      aneurysm repair: results of a randomized clinical study.
AB  - The purpose of this prospective, randomized study was to evaluate the effect of
      oral ofloxacin prophylaxis on endotoxin/cytokine release in aortic aneurysm
      repair, in 25 patients with infrarenal aortic aneurysm at a University hospital.
      Outcome parameters included complications after operation; endotoxin and
      endotoxin neutralizing capacity, IL-6, procalciton and neopterin. All patients
      had the standard perioperative antibiotic prophylaxis (2 g cefotiam). 12 patients
      randomly received oral ofloxacin prophylaxis (group 1) the day before the
      operation (200 mg/2x12h); 13 patients were controls (group 2). Data were analyzed
      by chi-square analysis, Mann-Whitney and Wilcoxon analysis. Ofloxacin had no
      effect on the occurrence of complications or on the peripheral endotoxin levels.
      Ofloxacin-treated patients showed increased endotoxin neutralizing capacity (ENC)
      30 min after clamping compared to controls (15.8+/-15 vs 262.8+/-709 p=0.005) and
      increased IL-6 levels preoperatively and 30 min after clamping. Patients with
      complications had significantly higher IL-6 levels early during the operation and
      postoperatively (30 min after clamping: 36.4+/-15.1 vs 18.8+/-11.9 pg/ml p=0.01;
      2nd postoperative day: 768+/-688 vs 225+/-322 pg/ml p=0.005). Ofloxacin
      prophylaxis had no effect on procalcitonin, or neopterin plasma levels. Neither
      procalcitonin nor neopterin could detect patients with complications IL-6 plasma
      levels predicted the occurrence of complications in aortic aneurysm repair. Oral
      ofloxacin prophylaxis may influence the ENC and IL-6 plasma levels but had no
      effect on complications, endotoxin and other inflammatory mediators.

PMID- 12797395
TI  - Prevalence and virologic consequences of HIV-1 genotype mutations detected in a
      cohort of 161 Italian patients receiving a nelfinavir-based highly active
      antiretroviral therapy.
AB  - A cross-sectional study was carried out in our tertiary care hospital between
      January 1998 and December 2001. All 161 consecutive patients naive to nelfinavir
      and who had received a nelfinavir-based highly active antiretroviral therapy
      (HAART) of at least 24-week duration were extrapolated from the 802 adult HIV
      infected subjects treated with antiretroviral therapy. All cases of virologic
      failure were considered and viral genotyped. Virologic failure occurred in 80 out
      of 161 nelfinavir-treated patients, all belonging to the experienced group. On
      the whole, only 11 patients (7%) developed the D30N substitution, whose 6 was in
      association with the N88D mutation. Among the 80 failed patients, the M184V
      mutation was detected in 52 (65%), while only 7 patients showed simultaneously
      the M184V, T215Y and K103N substitutions. In our HIV-infected population
      receiving a nelfinavir-based HAART, the D30N mutation has shown a low absolute
      frequency, while the detection of M184V substitution and the simultaneous
      occurrence of M184V, T215Y and K103N mutations were related to a more favorable
      virological response.

PMID- 12797396
TI  - DNA repair enzymes and cytotoxic effects of temozolomide: comparative studies
      between tumor cells and normal cells of the immune system.
AB  - O6-alkylguanine-DNA alkyltransferase (OGAT) and the mismatch repair system (MRS)
      play a crucial role in the susceptibility of tumor cells to the cytotoxic effects
      of agents that generate O6-methylguanine in DNA, including the triazene compound
      temozolomide (TMZ). Studies performed with peripheral blood mononuclear cells
      (MNC) showed that TMZ was scarcely active on lymphocyte functions not dependent
      on cell proliferation (e.g. NK activity and cytokine-mediated induction of CD1b
      molecule in adherent MNC). In contrast, TMZ depressed proliferation and
      lymphokine activated killer (LAK) cell generation in response to IL-2. In this
      case, a reasonably good inverse relationship was found between OGAT levels of MNC
      and their susceptibility to TMZ. This study also analyzed the ratio of the toxic
      effect of TMZ on MNC and on tumor cells (i.e. "Tumor-Immune Function Toxicity
      Index", TIFTI). A particularly favorable TIFTI can be obtained when OGAT levels
      are extremely high in MNC and markedly low in tumor cells. This holds true for
      MRS-proficient neoplastic cells, but not for MRS-deficient tumors. In conclusion,
      strategies aimed at modulating OGAT and MRS may improve the clinical response to
      TMZ. However, the use of OGAT inhibitors to potentiate the antitumor activity of
      TMZ might result in a concomitant increase of the immunosuppressive effects of
      the drug, thus reducing the relative TIFTI.

PMID- 12797398
TI  - Weekly docetaxel as second-line therapy for patients with advanced breast cancer
      resistant to previous anthracycline treatment.
AB  - This phase II trial evaluated the efficacy and toxicity of weekly docetaxel as
      treatment of advanced metastatic breast cancer patients resistant to prior
      anthracycline chemotherapy. After the first 18 patients, the initial dose (40
      mg/m2, 30-min i.v. infusion for 6 consecutive weeks, followed by 2-week rest) was
      reduced to 36 mg/m2 in the remaining 17 patients due to the incidence of toxicity
      (28% grade 3-4 asthenia). Overall response rate was 34% (95% CI, 19-50): two
      complete (6%) and ten partial responses (28%) were found. The median duration of
      response was 6.8 months, the median time to disease progression was 8.4 months,
      and the median overall survival was 13.6 months (median follow-up of 11.4
      months). Neutropenia was the only severe hematologic toxicity (17% of patients),
      whereas asthenia, nail, ocular and skin disorders were the most common
      nonhematologic toxicities. Only one death during further follow-up was related to
      toxicity (caused by pulmonary fibrosis). In conclusion, we found weekly docetaxel
      to be an active and safe chemotherapy regimen for patients with metastatic breast
      resistant to previous anthracyclines. This weekly regimen caused minimal
      myelosupression, while retaining significant activity against advanced breast
      cancer. Both factors provide attractive possibilities for the development of
      combination therapies incorporating weekly docetaxel. Nevertheless, the number of
      patients receiving either dose (40 and 36 mg/m2) which we studied is low and our
      results require confirmation on larger groups of patients.

PMID- 12797397
TI  - Randomized, controlled, multicenter phase III trial of standard-dose fluorouracil
      epirubicin-cyclophosphamide (FEC), compared with time-intensive FEC (FEC-G) and
      mitoxantrone-methotrexate-mitomycin C (MMM-G) in metastatic breast carcinoma.
AB  - The purpose of this multicenter phase III trial was to assess the impact of a
      time-intensification of FEC (fluorouracil, epirubicin, cyclophosphamide) and MMM
      (mitoxantrone, methotrexate, mitomycin C) regimens, supported by lenograstim (G
      CSF) on the objective response rate, time to progression and survival of patients
      with chemotherapy-naive metastatic breast cancer (mbc). Women with mbc were
      randomized to receive as first-line chemotherapy either standard-dose FEC (all
      doses in mg/m2): arm A (500, 75, 500 every 21 days), or time-intensified FEC-G:
      arm B (500, 75, 500 every 14 days), or time-intensified MMM-G: arm C
      (mitoxantrone 10, methotrexate 35 every 14 days and mitomycin C 10 every 28
      days), both with support of lenograstim (G-CSF 150 microg/m2/day s.c. for 10
      days). All study treatments were administered for six cycles. Eligible female
      patients were in the 31-70 year range with histologically proven mbc, and
      measurable or evaluable disease. An intent-to-treat analysis was performed. The
      overall response rate (CR + PR, intent-to-treat analysis) was significantly
      improved in the time-intensified FEC-G regimen (69%) in comparison with standard
      dose FEC (41%), p=0.002. Time-intensified MMM-G (51%) did not lead to a
      significant improvement in the response rate. The percentage of complete
      responses was significantly higher in the FEC-G arm as compared to standard-dose
      FEC (17% vs. 4.7%; p=0.002). The median duration was longer in the intensified
      dose arms without, however, achieving a statistically significant improvement.
      The median time to progression (TTP), and the median survival time did not differ
      between the three treatment arms. Grade 3-4 leukopenia was significantly higher
      (p<0.001) in the standard FEC regimen-treated patients. Thrombocytopenia was
      significantly higher (p<0.001) in both intensified regimens. Alopecia and
      mucositis were significantly more frequent in both anthracycline-containing
      regimens (p=0.003). Other hematological and non hematological toxicities were
      similar in the 3 treatment arms. The increase of dose-intensity of both FEC and
      MMM regimens improved activity, but not efficacy as compared to standard FEC
      regimen in our group of chemotherapy-naive, metastatic breast cancer patients.

PMID- 12797399
TI  - Chemotherapy and bio-chemotherapy in patients with advanced melanoma: combination
      therapy with a nitrosourea.
AB  - The treatment of advanced melanoma is still disappointing. In a multicenter
      randomized clinical trial to compare a chemotherapy (CT) with or without low
      doses of IL-2 and IFN (Bio-CT), the participating centers chose whether or not to
      add a nitrosourea, carmustine (BCNU) to the therapy. The aim of the present paper
      is to report the clinical results of the patients (pts) treated in both arms with
      BCNU. One hundred and seventy-six pts with advanced melanoma were enrolled in the
      study from 27 centers and a total of 18 pts also received BCNU in 3 centers. No
      further changes to the protocol criteria were allowed. One patient refused the
      treatment. No complete responses were observed. Irrespectively of the treatment
      arm, 9/17 pts showed a partial response to therapy (53%) (5/9 in the CT and 4/8
      in the BioCT arm). The most important adverse events observed were hematological:
      12 pts presented grade 3 (6 pts) or grade 4 (6 pts) leukocytopenia and 9 pts had
      grade 4 thrombocytopenia, all of which resolved spontaneously. The addition of a
      nitrosourea to CT or Bio-CT appears to improve response rates compared to the
      same regimens without nitrosourea. Patient tolerability is acceptable. Further
      studies using this combination are warranted.

PMID- 12797400
TI  - Experimental evidence for a female sex pheromone in Arrenurus manubriator (Acari:
      Hydrachnida; Arrenuridae).
AB  - We present experimental evidence for a water-borne female-produced sex pheromone
      in aquatic parasitengonine mites. Water that has contained adult female Arrenurus
      manubriator Marshall will elicit arrestant behaviour in conspecific adult males,
      and if the cue is sufficiently strong, the males will assume a readiness posture
      (with 4th pair of legs held over the back, bent anteromedially at the genuotibial
      joint) that is typically a precursor to coupling. Water that has not been exposed
      to female mites does not induce any behavioural response from male mites. Female
      conditioned water that has been passed through a C-18 column does not elicit any
      response from male A. manubriator, while the rehydrated residue from the column
      does induce arrestant behaviour and may result in the readiness posture. The
      results from the C-18 extraction indicate that the pheromone is nonpolar in
      nature.

PMID- 12797401
TI  - Mite growth on fungus under various environmental conditions and its potential
      application to biofilters.
AB  - The effects of relative humidity, temperature, pH and vapor-phase toluene
      concentration on Tyrophagus putrescentiae growth on Cladophialophora sp. were
      tested in controlled environmental chambers. It was observed that the mites were
      able to reproduce readily at relative humidities between 90% and 97% as well as
      on porous perlite support material pre-soaked in nutrient media of pH 2.5, 4 and
      7. Also, the presence of toluene at gas-phase concentrations of 500 to 2000 mg m(
      3) was found to be non-toxic to the mites. The mites, however, were unable to
      maintain a large population when the temperature was maintained at 14 degrees C,
      and overpopulation of the living space led to declines in mite population over
      time. Overall, it was found to be relatively simple to cultivate mites that may
      be used for fungal biomass control measures in biofilter applications.

PMID- 12797402
TI  - The growth of sheep scab lesions in relation to sheep breed and time of the year.
AB  - Numerically equal groups of between five and ten young Merino and Dorper sheep
      were artificially infested with sheep scab mites, Psoroptes ovis. Separate groups
      of sheep were infested during the early winter of two successive years as well as
      during the early summer of the second year. Lesion growth was measured at two
      weekly intervals for a period of six weeks during the first winter and for eight
      weeks during the second winter and in the summer. The rate of lesion growth and
      mean lesion size on Merino sheep was significantly greater than that on Dorper
      sheep at each two-weekly recording during the winter of both years. The rate of
      growth of the lesions did not differ significantly between the two sheep breeds
      during summer, although, with the exception of eight weeks post-infestation, the
      mean lesion size on Merino sheep was significantly larger than that on Dorper
      sheep at each assessment.

PMID- 12797403
TI  - Soil oribatid mite communities under three species of legumes in an ultisol in
      Brazil.
AB  - Oribatid mite densities in the topsoil and their activity at the soil surface
      were monitored under three species of perennial legume cover crops namely,
      Arachis pintoi, Macroptilium atropupureum and Pueraria phaseoloides, grass
      (Panicum maximum) and bare plots on three occasions in 1998 and 1999 in a derived
      savanna zone in Brazil. Both densities and activity at the soil surface were
      higher in the early but cool dry season in April 1998 than in the early wet but
      warm season in November 1998 and 1999. Three taxonomic groups of macropyline
      oribatid mites, namely Nothrus, Archegozetes and Masthermannia as well as a
      brachypyline taxon, Scheloribates were suggested as possible indicators of effect
      of legumes on soil biota because their populations increased under the legumes
      and/or the irresidues. Nothrus in particular increased in abundance more than any
      other taxon in the presence of residues of A. pintoi. Each legume supported a
      unique oribatid mite community in terms of species composition and relative
      abundance. The large numbers of Archegozeres trapped from all the legume and
      grass plots in April and November 1998 were also attributed to highly conducive
      conditions provided by the vegetation cover and their residues. The results
      suggest that the oribatid mite community of the study area was numerically stable
      as the peak populations of different species were not synchronized. Many
      taxonomic groups of pycnonotic brachypyline mites were absent. Legume cover
      crops, especially A. pintoi, and their residues have potential in restoring
      oribatid mite populations to precultivation levels.

PMID- 12797404
TI  - Host preference by Allothrombium pulvinum (Acari: Trombidiidae) larvae on aphids:
      Macrosiphum rosae, Aphis gossypii and Hyalopterus amygdali (Homoptera:
      Aphididae).
AB  - In this study aphid-plant association and its effect on host preference of
      parasitic Allothrombium pulvinum larvae was examined with multiple-choice tests.
      Host species selection, host size selection and superparasitism with mite larvae
      were studied with two-choice tests. Three aphid species were used: Macrosiphum
      rosae, Aphis gossypii and Hyalopterus amygdali. In multiple-choice tests, larvae
      of A. pulvinum showed no significant preference for any aphid-plant association
      when given M. rosae on rose, A. gossypii on cucumber and H. amygdali on apricot
      simultaneously. Two-choice tests showed that larval mites preferred H. amygdali
      to A. gossypii, but had no preference when offered a choice between A. gossypii
      and M. rosae or between H. amygdali and M. rosae. In host size selection and
      superparasitism tests, significantly more mites selected the larger host (M.
      rosae). Furthermore, parasitised H. amygdali were preferred to unparasitised
      ones.

PMID- 12797405
TI  - Susceptibility of populations of Banks grass mites (Acari: Tetranychidae)
      suspected of developing bifenthrin resistance from three maize fields.
AB  - Banks grass mite, Oligonychus pratensis (Banks), from three Texas maize fields
      were assayed for bifenthrin resistance following poor field control in 1995.
      Laboratory bioassays showed the field mites to be 3- to 23-fold more tolerant to
      bifenthrin than the susceptible laboratory culture. Comparison of LC50 values to
      assays with bifenthrin from 1985 to 1993 indicated no statistically significant
      changes in mite resistance. However, high LC90 values in 1995 suggest possible
      resistance development. The percentages of resistant mites from the three fields
      in 1995 were calculated to be 4.7%, 17.9%, and 30.9%. The Banks grass mite
      population exhibiting the highest level of tolerance to bifenthrin was further
      assayed to evaluate tolerance levels to other insecticides alone and in
      combination with synergists and insecticides. A high level of tolerance existed
      in the 1995 'bifenthrin-selected' Banks grass mite strain to bifenthrin,
      dimeothate, and amitraz. The combination of bifenthrin or dimethoate with a
      synergist indicated changes in the ability of the more resistant 1995 mites to
      detoxify insecticides. The activity of a dimethoate + bifenthrin mixture and a
      three way mixture of dimethoate, bifenthrin, and piperonyl butoxide caused 5- and
      38-fold increase in toxicity against the more resistant Banks grass mite.

PMID- 12797406
TI  - The possible role of Varroa destructor in the spreading of American foulbrood
      among apiaries.
AB  - The aim of this investigation was to establish whether Varroa destructor can play
      a role in the transmission of Paenibacillus larvae larvae spores from infected to
      healthy bee colonies. Mites, collected from an Apis mellifera carnica colony
      heavily infected with American foulbrood and treated with Apistan, were suspended
      in distilled water and treated in three different ways:homogenizing, shaking and
      stirring, or sonication. The resulting fluid samples were transferred onto
      selective agar medium. All culture plates showed colonies that could be
      identified as P.l. larvae. In view of the numbers of spores they can carry, it is
      concluded that mites may transmit American foulbrood from infected to healthy bee
      colonies.

PMID- 12797407
TI  - Laboratory evaluation of some plant essences to control Varroa destructor (Acari:
      Varroidae).
AB  - This research was conducted to evaluate acaricidal effects of some plant essences
      on Varroa mites and the possibility of their usage for Varroa control. First,
      live Varroa mites were obtained from adult honeybees with CO2 in a newly designed
      apparatus. Thyme, savory, rosemary, marjoram, dillsun and lavender essences at
      concentrations of 2 and 1 g/100 g (w/w), caused a mite mortality rate of more
      than 97% and 95%, respectively. Also spearmint at 2 g/100 g was able to kill more
      than 97% of Varroa mites. When sprayed on worker honeybees infected with mites,
      thyme, savory, spearmint and dillsun essences at 2 g/100 g (w/w) caused 43-58%
      Varroa mortality. Toxicity of thyme, savory and spearmint essences for worker
      honeybees was not significantly different from that of controls (acetone and
      water), but dillsun essence caused 12% honeybee mortality. These results showed
      that essences of thyme, savory and spearmint have acaricidal properties that
      could be used for controlling Varroa in honeybee colonies.

PMID- 12797408
TI  - Kinetics of ingested host immunoglobulin G in hemolymph and whole body
      homogenates during nymphal development of Dermacentor variabilis and Ixodes
      scapularis ticks (Acari: Ixodidae).
AB  - Patterns in the utilization of host immunoglobulin G (IgG) during nymphal
      development differed between Dermacentor varibilis (Say) and Ixodes scapularis
      Say ticks. In unfed nymphs of D. variabilis, host IgG was readily detectable in
      both hemolymph and whole body homogenates. In unfed nymphs of I. scapularis, host
      IgG was absent in hemolymph and at very low concentrations in whole body
      homogenates. Host IgG in unfed nymphs was undoubtedly the remnants of IgG
      acquired during the larval bloodmeal that persisted through metamorphosis to the
      nymphal stage. In both tick species, host IgG crossed the midgut into the
      hemocoel during the latter phases of engorgement. Concentrations of host IgG in
      I. scapularis declined considerably after replete nymphs molted to the adult
      stage. In contrast, concentrations of host IgG in D. variabilis remained elevated
      throughout metamorphosis to the adult stage. When larval D. variabilis were fed
      on a rat, then 2 months later as nymphs on a rabbit, the rat IgG ("old IgG")
      present in unfed nymphs was totally replaced by rabbit IgG ("new IgG") within 2 d
      of nymphs attaching to the rabbit. Presumably, the old IgG acquired from a
      previous bloodmeal was secreted via saliva into the new host.

PMID- 12797409
TI  - Bovine mastitis in selected areas of southern Ethiopia.
AB  - A study on bovine mastitis, designed to determine the causal agents, prevalence
      of infection and impact of risk factors in three cattle breeds, was conducted in
      selected areas of southern Ethiopia. A total of 307 lactating and non-lactating
      cows, of which 162 were indigenous Zebu, 85 Jersey and 60 Holstein-Friesian. were
      examined by clinical examination and the California mastitis (CMT) test. Of
      these, 40.4% were positive by CMT and bacteriology for clinical or subclinical
      mastitis, with prevalence rates of 37.1% and 62.9%, respectively. Out of 1133
      quarters examined, 212 (18.7%) were found to be infected, 83 (39.21%) clinically
      and 129 (60.8%) subclinically. The prevalence of mastitis was significantly
      higher in Holstein-Friesian than in indigenous Zebu, in non-lactating cows than
      in lactating cows, in the early lactation stage than in the mid-lactation stage,
      in cows with lesions and/or tick infestation on skin of udder and/or teats than
      in cows without this factor, and in the wet season than in the dry season.
      Mastitis increased with parity number (R = 0.9). Of 248 CMT and clinically
      positive udder quarter samples analysed microbiologically, 212 were culturally
      positive for known mastitis pathogens and 36 were negative. Of the 199 positive
      samples. Staphylococcus accounted for 39.2%. Streptococcus for 23.6%, coliforms
      for 14.1%, Micrococcus and Bacillus species for 8.0% each and Actinomyces or
      Arcanobacterium (Corynebacterium) for 7.0%. It was concluded that there was a
      high prevalence of clinical and subclinical mastitis, mainly caused by
      Staphylococcus aureus, Streptococcus agalactiae and Escherichia coli, in this
      study area.

PMID- 12797410
TI  - Epidemiological studies on gastrointestinal parasitic infections of lambs in the
      Coastal Savanna regions of Ghana.
AB  - The types of gastrointestinal parasites (Eimeria and helminths) encountered by 70
      lambs and the seasonal pattern of both Eimeria and strongylate infections in
      these lambs in the derived Coastal Savanna were followed for three years. Eimeria
      oocysts and helminth eggs were detected in the faeces of lambs at the same time,
      indicating the concurrence of both Eimeria and helminth infections. Eimeria
      oocysts were first seen in the lambs 20 days after birth (DAB) and the level of
      oocyst output increased by the fourth week. Eimeria species identified in the
      lambs were E. parva, E. pallida, E. faurei, E. ahsata, E. bakuensis, E.
      intricata, E. granulosa, E. ovinoidalis and, occasionally, E. marsica, E.
      ovinoidalis, the most pathogenic species, dominated the oocyst output during the
      early part of the life of the lambs. Strongyloides papillosus eggs appeared at 46
      DAB, preceding strongylate nematode eggs, which were seen at 57 DAB and those of
      Moniezia at 69 DAB. The pattern of Eimeria oocyst output paralleled that of the
      worm egg output, and high oocyst and strongylate worm egg counts corresponded
      with the period of high rainfall during the study period. Although oocyst and
      worm egg output fluctuated, high Eimeria oocyst counts were seen again in the
      lambs when they were 1 and 2 years old. Haemonchus species formed 71% of the
      infective larvae revealed by larval culture.

PMID- 12797411
TI  - Albendazole resistance in gastrointestinal nematode parasites of cattle in
      Bangladesh.

PMID- 12797412
TI  - Privatization of veterinary services in developing countries: a review.
AB  - Increasing fiscal constraints on the government, a lackadaisical performance by
      public sector animal health and breeding services and pressure from donor
      partners have prompted the governments of various developing countries to rethink
      the role of the public sector in the provision of veterinary services. Various
      countries have started to implement, or have already implemented, privatization
      of some veterinary services. The results are mixed. It is established that
      private provision alone is not optimal, and a blend of private and public sector
      veterinary services is required to utilize the virtues of both. The privatization
      process has also begun in India. Certain state governments in India are pursuing
      a cost recovery approach and are encouraging private practitioners to cope with
      the financial constraints and to deliver broad and effective animal health and
      breeding services. This paper considers the global aspects of the privatization
      of veterinary services as well as the scenario in India, so as to gain an insight
      into the very complex and debatable issue of privatization of veterinary
      services.

PMID- 12797413
TI  - The impact of tick control on the productivity of indigenous cattle under ranch
      conditions in Uganda.
AB  - The impact of tick control on the productivity of indigenous cattle was
      investigated in three herds of East African shorthorn Zebu and Zebu x Ankole
      (Nganda) breeds, maintained under three tick management systems practised under
      ranch conditions: twice-a-week dipping, once-a-month dipping, and no tick
      control. The milk production and the growth rates of pre-weaned and post-weaned
      calves were monitored once a month over a period of 34 months. Milk offtake was
      23% higher during the heavy rainy seasons than in the long dry seasons. Twice-a
      week dipping increased the milk offtake by 21% in the second year of study and
      prolonged the duration of lactation in cows. Similarly, twice-a-week dipping
      increased the pre-weaning growth rate by 39% in the second year of study, but had
      no significant effect on the post-weaning growth rate. Generally, the growth rate
      of calves were greatest during the heavy rainy seasons and least during the long
      dry seasons. These results provide a basis for assessing the losses under
      different tick management systems in the various production systems.

PMID- 12797414
TI  - Sperm motion characteristics of Garole rams raised for a prolonged period in a
      semi-arid tropical environment.
AB  - The Garole is a prolific but less well known and rare breed of small sheep found
      in the hot and humid Sunderban region of West Bengal. An ability to breed
      throughout the year and to graze in knee-deep water, resistance to foot rot and a
      strong mothering instinct are some of the special features of this breed. Garole
      rams could provide germplasm to incorporate prolificacy traits by artificial
      insemination of the nonprolific sheep breeds found in abundance in the semi-arid
      and arid tropical climates of India. The aim of the present study was to evaluate
      the semen production by Garole rams maintained in a semi-arid climate for three
      years and to objectively assess their semen quality by a computer-assisted sperm
      analysis technique. The donor rams were randomly selected each year from the
      original flock procured from their natural habitat or from the offspring born at
      the Institute farm. Semen was collected weekly for three weeks each autumn for
      three consecutive years from 8 rams each year. The overall means (SD) of the
      traits that did not differ significantly with age or year were volume,
      concentration, curvilinear velocity, average path velocity, amplitude of lateral
      head displacement, beat frequency, motility and the percentages of rapid motile
      sperms and of slow motile sperms. The age of the rams had a significant effect
      (p<0.05) on the straight-line velocity but this was not significantly affected by
      the length of exposure to the semi-arid climate. However, the age and year had
      significant effects (p<0.05) on linearity, straightness and the percentage of
      medium motile sperms. It was concluded that Garole rams are capable of producing
      good-quality semen even after a prolonged period of exposure to a semi-arid
      tropical climate.

PMID- 12797415
TI  - Feeding strategies for rearing replacement heifers in small-scale dairy
      production systems in the highlands of Central Mexico.
AB  - The growth of Holstein heifers in the campesino dairy systems in the highlands of
      Mexico was evaluated in three feeding strategies. Thirty-three heifers from 11
      farmers, grouped according to strategy, were weighed every 14 days for 28 weeks.
      The live weight change over each 14-day period was estimated by individually
      regressing live weight over period, taking the regression coefficient as an
      unbiased estimate of live weight change. Regression coefficients were analysed as
      a randomized design with feeding strategies as treatments. Strategies were as
      follows: S1: grazed or cut pasture all year, maize silage and maize straw in the
      dry season, and 1.0-1.5 kg concentrate/heifer per day. S2: maize straw in the dry
      season, cut pasture forage, grazing of native grass, weeds from maize fields, and
      1.0-1.5 kg concentrate/heifer per day. S3: maize straw in the dry season, grazed
      native grasses and weeds in the rainy season. Live weight gains were: S1, 0.511
      kg/heifer per day; S2, 0.271 kg/heifer per day; and S3, 0.252 kg/heifer per day.
      Despite the better gains in S1, they are 24% below recommendations, arriving to
      service at 20 months of age. Not rearing their replacements may be a better
      alternative for campesino farmers under current economic conditions.

PMID- 12797416
TI  - Genetic analysis of growth traits in Muzaffarnagari sheep.
AB  - Data on 4112 Muzaffarnagari sheep, maintained at the Central Institute for
      Research on Goats, Makhdoom, Mathura, India, and recorded between 1976 and 1999,
      were analysed to study the growth-related traits and their genetic control. The
      average weights at birth, and at 12 months of age were 3.1 +/- 0.2 and 28.0 +/-
      0.6 kg, respectively. The pre- and post-weaning average daily weight gains were
      127.8 +/- 3.3 g and 49.4 +/- 1.6 g. and the associated growth efficiencies were
      3.59 +/- 0.08 and 0.95 +/- 0.03. Significant differences associated with the year
      of lambing were observed in body weight, weight gain and efficiency in weight
      gain at different stages of growth. The lambs born in the dam's second parity
      were generally of heavier weight and higher daily weight gain than those born in
      other parities. Males were heavier and had a higher weight gain than females at
      almost all stages of growth and the differences tended to increase with age.
      Single-born lambs had a distinct advantage over those born in multiple births at
      all stages of growth. The heritabilities of all body weights, weight gains and
      efficiency in weight gains at different stages of growth were moderate (0.18
      0.26), except for birth weight, which was of low heritability (0.068 +/- 0.01).
      The phenotypic and genetic correlations among the different body weights were
      positive and high, except for birth weight. The genetic correlation of the pre-
      and post-weaning average daily weight gains with body weights were high and
      positive.

PMID- 12797417
TI  - Effects of high-tannin sorghum and bentonite on the performance of laying hens.
AB  - The effects of feeding high-tannin sorghum (HTS) (5% catechin equivalents (CE))
      on the performance of laying hens were examined in two experiments. In experiment
      1, the effects of including varying levels of HTS in layer diets were
      investigated. Sixty-three Isabrown hens were randomly assigned to each of the
      seven diets over a period of 56 days. In experiment 2, the effects of bentonite
      on the utilization of HTS (3.74% CE) by laying hens were investigated. Forty-five
      Isabrown hens were randomly assigned to each of five diets over a period of 42
      days. In both experiments, weekly measurements were made for feed intake (FI),
      percent hen-house production (% HHP), egg weight and egg specific gravity (ESG).
      The results of experiment 1 showed that the different sorghum inclusion levels
      had no effect (p > 0.05) on HHP, egg weight and ESG, while those of experiment 2
      showed that maize and LTS diets gave similar weight gain. FI and FE (p > 0.05).
      However, HHP was higher (p < 0.05) for the LTS diet than for the other diets. The
      addition of bentonite of 0.25% or 0.5% to the HTS diet did not improve (p > 0.05)
      layer performance. When all the results were considered together, it was
      concluded that HTS can be used in layer diets without adverse effects on
      performance. The use of bentonite to deactivate sorghum tannins is not considered
      necessary.

PMID- 12797418
TI  - Ceramic drug delivery: a perspective.
AB  - Different ceramic substances are offered in the market as bone substitute
      materials. These include monophasic calcium phosphate ceramics of
      tricalciumphosphate (TCP) or hydroxyapatite (HA), biphasic calcium phosphate
      ceramics and multiphasic bio-glasses synthetic calcium phosphate cements.
      Ceramics with appropriate three-dimensional geometry are able to bind and
      concentrate bone morphogenetic proteins in circulation and may become
      osteoinductive (capable of osteogenesis) and can be effective carriers of
      bioactive peptide or bone cell seeds and are therefore potentially useful in
      tissue engineering and drug delivery. An attempt has been made to review various
      drug delivery applications of ceramics.

PMID- 12797419
TI  - Biological reactions to a poly(L-lactide)-hydroxyapatite composite: a study in
      canine mandible.
AB  - In this study, bone response, possible use and ultimate fate of a chemically
      synthesized poly(L-lactide)-hydroxyapatite (PLLA-HA) composite was experimented
      in canine mandible. Bilateral mandibular second premolars were extracted in four
      dogs. The PLLA-HA composite was placed into left surgical sites, and right
      extraction sites were used as controls. After three months of healing, bone
      specimens were harvested from each animal and processed for histological
      evaluation. Bone uptake of methylene diphosphonate (99mTc-MDP) was calculated as
      indicators of osteoblastic activity in the surgical sites. Histological
      evaluation and the amount of 99mTc-MDP uptake showed that all surgical sites had
      similar levels of cellular activity and the material was biocompatible. The
      experimental PLLA-HA composite studied is safe to be used as a small-defect
      filler in applications such as repair of alveolar defects, ridge augmentations,
      and sinus lift procedures.

PMID- 12797420
TI  - The effect of fiber reinforcement type and water storage on strength properties
      of a provisional fixed partial denture resin.
AB  - Fracture resistance of provisional restorations is an important clinical concern.
      This property is directly related to transverse strength. Strengthening of
      provisional fixed partial dentures may result from reinforcement with various
      fiber types. This study evaluated the effect of fiber type and water storage on
      the transverse strength of a commercially available provisional resin under two
      different conditions. The denture resin was reinforced with either glass or
      aramid fiber or no reinforcement was used. Uniform samples were made from a
      commercially available autopolymerizing provisional fixed partial denture resin.
      Sixteen bar-shaped specimens (60 x 10 x 4 mm) were reinforced with pre-treated
      epoxy resin-coated glass fibers, with aramid fibers, or with no fibers. Eight
      specimens of each group, with and without fibers, were tested after 24 h of
      fabrication (immediate group), and after 30-day water storage. A three-point
      loading test was used to measure the transverse strength, the maximal deflection,
      and the modulus of elasticity. The Kruskal-Wallis Analysis of Variance was used
      to examine differences among the three groups, and then the Mann-Whitney U Test
      and Wilcoxon Signed Ranks Test were applied to determine pair-wise differences.
      The transverse strength and the maximal deflection values in the immediate group
      and in the 30-day water storage group were not statistically significant. In the
      group tested immediately, the elasticity modulus was found to be significant (P =
      0.042). In the 30-day water storage group, all the values were statistically
      insignificant. The highest transverse strength was displayed by the glass
      reinforced resin (66.25MPa) in the immediate group. The transverse strength value
      was 62.04MPa for the unreinforced samples in the immediate group. All the
      specimens exhibited lower transverse strength with an increase in water immersion
      time. The transverse strength value was 61.13 MPa for the glass-reinforced resin
      and was 61.24 MPa for the unreinforced resin. The aramid-reinforced resin
      decreased from 62.29 to 58.77 MPa. The addition of fiber reinforcement enhanced
      the physical properties (the transverse strength, the maximal deflection, the
      modulus of elasticity) of the processed material over that seen with no addition
      of fiber. Water storage did not statistically affect the transverse strength of
      the provisional denture resin compared to that of the unreinforced resin. The
      transverse strength was lowered at water storage but it was not statistically
      significant. The transverse strength was enhanced by fiber addition compared to
      the unreinforced resin. The glass fiber was superior to the other fiber. Also the
      modulus of elasticity was enhanced by fiber addition compared to the unreinforced
      resin.

PMID- 12797421
TI  - The development of porous alginate/elastin/PEG composite matrix for
      cardiovascular engineering.
AB  - The development of suitable three-dimensional matrices for the maintenance of
      cellular viability and differentiation is critical for applications in tissue
      engineering and cell biology. To this end, gel matrices of different proportions
      of alginate/elastin/polyethylene glycol (Alg/Ela/PEG) were prepared and examined.
      The composite matrix membranes were evaluated for their porous scaffold using
      SEM, enzymatic degradation and water content. An equal blend of Alg/Ela with a
      ratio of Alg/Ela: PEG (7:3) was selected for fabricating Alg/Ela/PEG scaffolds
      for this study. The Alg/Ela/PEG membranes fabricated at 20 degrees C and - 20
      degrees C had a mean surface pore size of 35-45 microm. However, their
      ultrastructures had shown bigger pore structures (60-75 microm) compared to their
      surface. It is interesting to note that the membranes of Alg/Ela/PEG prepared at
      20 degrees C had larger ultrastructural pores than that of membranes prepared at 
      20 degrees C. Further, the SEM studies revealed that in the absence of PEG the
      composite membranes of Alg/Ela formed with less porous structures. The water
      content of membranes prepared at 20 degrees C was higher with Alg/Ela/PEG (61.6
      +/- 4.8%), compared to Alg/Ela (49.9 +/- 0.3%). The enzymatic degradation and
      water content studies also revealed that the membranes fabricated at - 20 degrees
      C had high water uptake and low enzymatic degradation, as that of the membranes
      prepared at 20 degreees C. In other words the larger pore structured membranes
      had less water content and high degradation profile. This study proposes that
      this novel composite matrix produces a hierarchical structure that is useful for
      generating tissue scaffolds for repairing the failing cardiac muscles. However,
      more detailed investigations with cytocompatibility studies are needed to find
      applications.

PMID- 12797422
TI  - Blood compatibility of titanium oxides with various crystal structure and element
      doping.
AB  - BACKGROUND: Titanium oxides are known to be good hemocompatible, therefore they
      are suggested as coatings for blood contacting implants. But little is known
      about the influence of physical characteristics like crystal structure, roughness
      and electronic state on the activation of blood platelets and the blood clotting
      cascade. METHODS: Titanium oxide films were produced by metal plasma deposition
      and implantation in the form of rutile, crystalline and nanocrystalline anatase +
      brookite and amorphous TiO2. The redox potential was reduced by implantation of
      chromium ions, the Fermi level of the semiconductive oxide was shifted by ion
      implantation of the electron donor phosphorous. Hemocompatibility was determined
      by measuring the adhesion of blood platelets, their P-selectine expression, and
      of the blood clotting time on these samples. RESULTS: The crystalline titanium
      oxides had a slightly higher activation of the clotting cascade but lower
      platelet adhesion than nanocrystalline and amorphous titanium oxides. The surface
      roughness below 50 nm had no obvious effect. Both, implantation of phosphorous or
      chromium ions, strongly reduced the activation of the clotting cascade, but only
      the phosphorous implanted surface also showed a reduced platelet activation,
      whereas platelet adhesion and activation was strongly increased on the chromium
      implanted surfaces. CONCLUSION: Phosphorous doping of rutile TiO2 can increase
      its hemocompatibility, both concerning blood platelets and blood clotting
      cascade, but the biochemical mechanism has to be worked out.

PMID- 12797423
TI  - Water sorption, solubility and dimensional changes of denture base polymers
      reinforced with short glass fibers.
AB  - The aim of this study was to determine water sorption, solubility and dimensional
      stability of injection and compression-molded polymethyl methacrylate based
      denture base polymer that was reinforced with various concentrations and lengths
      of E-glass fibers. For water sorption and solubility, 20 test groups with
      different fiber contents and lengths of fibers were prepared. Test specimens
      without fibers were used as a control. The water sorption and solubility was
      measured after 90 days water storage. For dimensional stability, rhombic test
      specimens were prepared and the dimensional changes were measured after
      processing, drying and storing in water for 4 days and 30 days and were compared
      with those on the brass model. The water sorption and solubility of injection
      molded denture base polymer was lower compared to compression-molded specimens (p
      < 0.05). The dimensional accuracy of denture base polymer was not affected with
      fiber reinforcement (p > 0.05).

PMID- 12797424
TI  - The target of therapies: pathophysiology of gastroesophageal reflux disease.
AB  - Recognition of the importance of anatomical and mechanical factors in the
      pathogenesis of GERD has led to attempts that modify these mechanisms by
      endoluminal therapies. Although these alterations of EGJ anatomy and function
      appear minor at first glance, one must be cautious not to upset the delicate
      balance maintained by this complex anatomic zone. Performing a procedure that
      effects retrograde flow will inevitably also affect antegrade flow to some
      degree. The challenge will be to find a middle ground whereby GERD symptoms are
      not exchanged for symptoms such as dysphagia and gas bloat. With respect to
      endoluminal therapies, the authors are at an early stage of development and much
      more work is needed to define the relevant mechanical variables that need to be
      modified and to define the patient populations most appropriate for these
      interventions.

PMID- 12797425
TI  - Historical perspectives on the treatment of gastroesophageal reflux disease.
AB  - The current vogue in the historical evolution of the management of the problem of
      reflux is represented by augmentation procedures for the lower esophageal
      sphincter. Rather than employ a transperitoneal approach, these are directed at
      the sphincter by the transesophageal route and include stitching, collagen
      injection and radio-frequency-induced fibrosis. It is however probable that these
      techniques will suffer all the drawbacks of any mechanical intervention but
      somewhat decrease the morbidity of open, albeit minimally invasive surgery.
      Similarly, a specific pharmacotherapeutic probe targeting the lower esophageal
      sphincter, while long fantasized, remains to be identified.

PMID- 12797427
TI  - An overview of the success and failure of surgical therapy: standards against
      which the outcome of endoscopic therapy is measured.
AB  - Medical therapy for reflux disease has evolved from frequent antacid use to once
      daily proton pump inhibitor therapy. Despite the efficacy of these agents in
      healing erosive esophagitis, there are several short-comings with medical therapy
      including incomplete symptom relief, the need for continuous maintenance therapy,
      and cost. Endoscopic and laparoscopic treatments for reflux disease are appealing
      because they could reduce or eliminate the need for chronic maintenance therapy
      with medications. While there is evidence of high quality on the efficacy of
      medical therapy from randomized controlled trials, data on endoscopic procedures
      and surgery is more limited. This article summarizes the needed studies and the
      standards against which these procedures should be measured.

PMID- 12797426
TI  - Overview of medical therapy for gastroesophageal disease.
AB  - The last twenty years have seen an evolution of much improved strategies in the
      medical treatment of GERD. Current therapy is targeted at acid suppression, to
      deal with consequences of mucosal injury and afford resolution of symptoms. Given
      their modest efficacy, there is no longer much support for initial treatment with
      H2RAs. PPIs have been shown to provide the highest levels of symptom relief and
      esophageal healing, in addition to preventing relapse and complications. With
      this class of agents, the clinician is able to prescribe a drug that is as highly
      effective as surgery for the purpose intended, without worrying about long term
      sequelae of acid suppression. It appears that patients with extraesophageal GERD
      must be treated with higher doses of pharmacologic therapy, principally with the
      PPIs, for longer periods of time to achieve complete relief of symptoms when
      compared to patients with heartburn and erosive esophagitis. There is still no
      clear consensus as to whether aggressive acid suppression alters the natural
      history of Barrett's esophagus. Based on their initial success, it appears that
      the next generation of evolving medical therapies will continue to play an
      important role in the management of GERD. The outcome from medical therapy is the
      standard against which the results of the novel endoscopy anti-reflux treatments
      will be measured.

PMID- 12797428
TI  - Bard EndoCinch: the device, the technique, and pre-clinical studies.
AB  - There is, of course, room for improvement. More work is needed to make endoscopic
      suturing easier, quicker and more reliable. The single most important next goal
      is to construct a device, which can place multiple stitches without the need to
      remove the endoscope between each stitch. Devices, which can place two stitches
      in one go, would be a start. The development of double stitch and multiple stitch
      devices has been described earlier. The authors are pleased to see two
      alternative commercial endoscopic sewing devices appear at the last DDW which
      place two stitches without needing to withdraw the endoscopes--they use a double
      needle method.

PMID- 12797429
TI  - Endoscopic suturing for gastroesophageal reflux disease: clinical outcome with
      the Bard EndoCinch.
AB  - From a review of the single peer reviewed published report and the brief
      preliminary studies presented in abstract form, the BARD EndoCinch procedure
      seems safe and demonstrates an acceptable efficacy for symptom control during
      short-term follow-up. Most patients (about 2 out of 3) do well with improvement
      of GERD symptoms during the first post-procedural year. This benefit may wane
      over time. Objective benefit is lacking with the minority of treated individuals
      achieving normalization of 24-hour total acid exposure, and no significant effect
      has been seen in healing of esophagitis. This may focus the treatment towards
      that group of GERD patients with mild or non-erosive disease. The authors have no
      information that the endoscopic therapy could prevent reflux-related
      complications, and long-term data is awaited from accumulated clinical experience
      to establish the maintenance profile of this novel treatment. The outcomes from
      the sham trial, and long-term follow-up data will help to define the role of this
      anti-reflux therapy. The authors need additional studies to define the effect of
      endoluminal plication on the function of the lower esophageal sphincter to
      optimize its benefit for patients.

PMID- 12797430
TI  - Wilson-Cook sewing device: the device, technique, and preclinical studies.
AB  - Endoscopic treatment of GERD is still in its infancy, however the potential
      benefits of an endoscopic treatment for GERD are great. These procedures can be
      performed on an outpatient basis, without the risks of general anesthesia. The
      absence of abdominal incisions eliminates the morbidity of wound infections and
      hernia formation. The procedures are certainly less painful than laparoscopic or
      open surgery for reflux disease. These procedures might even be more cost
      effective than long-term acid suppression. These benefits make endoscopic
      treatment for reflux disease an appealing alternative. While the ideal endoscopic
      therapy has not been developed, all of these approaches have promise for the
      future and with further study the role of endoscopic therapy for GERD will
      continue to be defined.

PMID- 12797431
TI  - Endoscopic full-thickness plication: the device, technique, pre-clinical and
      early clinical experience.
AB  - The endoscopic full-thickness plication device is designed to inhibit reflux with
      a single plication near the gastroesophageal junction. Full-thickness plication
      of the proximal stomach may improve the competency of the gastroesophageal
      barrier by restoring the valvular mechanism of the gastroesophageal junction.
      Other potential mechanisms include alteration of the angle of His, and reduction
      of the compliance of the gastric cardia and fundus. The procedure is easily and
      safely performed and, in the human pilot study, has been shown to reduce symptoms
      and medication use associated with gastroesophageal reflux disease.

PMID- 12797432
TI  - Microvasive gastric stapler: the device, technique, and preclinical results.
AB  - Antireflux surgery was initiated in 1950 with the Allison repair, improved in the
      1970s with the introduction of the partial and complete fundoplication, and
      performed laparoscopically in the 1990s. Today the challenge is to perform the
      procedure endoscopically. The physiology of the gastroesophageal barrier and the
      causes and consequences of its failure are discussed. The experimental
      development of an intraluminal transgastric valvuloplasty is discussed, and
      comments are made about the future role of endoscopic repairs.

PMID- 12797433
TI  - The Stretta procedure: device, technique, and pre-clinical study data.
AB  - The initial concept of delivering RF energy to the gastroesophageal junction for
      the treatment of GERD was based on the well-established safety profile and
      scientific clinical evidence supporting the effectiveness of this technology in
      other disease states. As described in this article, the Stretta procedure is an
      endoluminal procedure inducing collagen tissue contraction, remodeling, and
      modulation of the triggering threshold for transient LES relaxations. The
      preclinical experience with this device included feasibility studies to determine
      optimal treatment parameters and device design. This was followed by longitudinal
      animal studies to elucidate the mechanism of safety and effect of this
      intervention as it relates to LES physiology and histopathology. In these
      studies, RF elevated the LES pressure and gastric yield pressure in a porcine
      model of botulinum toxin induced LES hypotension. The elevation in GYP more than
      6 months was confirmed in a subsequent evaluation. Thickening of the LES after RF
      delivery has been demonstrated using histopathological evaluation and EUS.
      Additionally, using a canine model of triggered transient LES relaxations
      (tLESR), RF significantly reduced the frequency of tLESRs and reflux events.
      Additional evaluation was performed in human subjects undergoing esophagectomy,
      confirming feasibility and Histopathologic results of the treatment. Subsequent
      clinical trials confirm the safety and mechanism of action data of these pre
      clinical studies and are presented in this publication.

PMID- 12797434
TI  - Clinical experience with the Stretta procedure.
AB  - The benchmarks in GERD therapy comprise the commonly prescribed anti-secretory
      drugs (H2RAs and PPIs) and anti-reflux surgery. Although drugs are typically
      safe, cost and patient compliance are challenges to long-term management.
      Furthermore, while heartburn may be controlled with aggressive medical therapy,
      other symptoms such as regurgitation may persist, reducing patient satisfaction
      and adversely affecting quality of life. Surgical anti-reflux procedures, most
      commonly laparoscopic Nissen fundoplication, improve GERD symptoms and normalize
      esophageal acid exposure in most patients. Patient perception of the potential
      risk of abdominal surgery and general anesthesia may limit willingness to undergo
      surgery resulting in only a small portion of GERD sufferers that actually undergo
      anti-reflux surgery each year. Overall, the Stretta procedure is well tolerated,
      with an acceptably low incidence of complications and obviates the need for anti
      secretory drug therapy for most patients at the 6- and 12-month follow-up. GERD
      symptom scores, heartburn, satisfaction, and SF-36 scores significantly improve
      over the baseline and this effect lasts at least 12 months. The symptomatic
      improvement after Stretta at 12 months in one trial (GERD score, 27 to 9) is
      similar to that reported by Velanovich after fundoplication (GERD score, 27 to
      3). Furthermore, the significant reduction in median esophageal acid exposure
      time (distal 10.6% to 6.2%, proximal 1.9% to 0.9%), provides objective evidence
      of an anti-reflux effect. Although the reported studies have been non-randomized,
      the objective improvement observed in esophageal acid exposure and the
      persistence of GERD symptom score improvement with repeated measure analysis over
      a course of 12 months make a significant placebo effect unlikely. Stretta is a
      promising new technology for the treatment of GERD that should be considered for
      patients who wish to discontinue a lifelong anti-secretory medication regimen or
      who have incomplete GERD symptom control on drugs, but are not yet accepting anti
      reflux surgery.

PMID- 12797435
TI  - The history and future of implantation therapy for gastroesophageal reflux
      disease.
AB  - The initial development of endoscopic implantation techniques for the treatment
      of gastroesophageal reflux disease in the 1980s helped set the stage for current
      implantation techniques and studies, which now include more than 500 patients.
      The relative simplicity of these techniques adds to their attraction. Ultimately,
      multiple factors, including therapeutic efficacy durability, safety, simplicity,
      and cost-effectiveness, will determine clinical application of these techniques.
      This article focuses on transoral endoscopic implantation, although surgical,
      transcutaneous, and other endoscopic routes have been used as well.

PMID- 12797436
TI  - Plexiglas (polymethylmethacrylate) implantation: technique, pre-clinical and
      clinical experience.
AB  - Over the past few decades, a great scientific effort has been made to treat
      gastroesophageal reflux disease (GERD). This reflects a trend in modem medicine
      toward optimizing quality of life, reducing health-related lost working hours,
      and minimizing costs of chronic treatments. It also reflects a revived interest
      in diseases that can be studied using novel equipment and that can be cured using
      minimally invasive techniques. In an effort to further minimize surgical trauma,
      novel endoscopic techniques are beginning to challenge the standard therapeutic
      approach to GERD.

PMID- 12797437
TI  - Gatekeeper Reflux Repair System: technique, pre-clinical, and clinical
      experience.
AB  - The Gatekeeper Reflux Repair System is a new, promising endoscopic anti-reflux
      therapy. It has now been shown that it is possible to implant hydrogel prosthesis
      in the submucosa of the esophagus of humans. The pilot study in humans showed
      that it is a safe technique and no prostheses migrated into the mediastinum. With
      the help of endoscopic ultrasonography, each prosthesis was followed during the 6
      month pilot study. After finishing this pilot study, new multi-center studies
      have been initiated with implantation of more prostheses to increase efficacy.
      One of the definite advantages over the other endoscopic treatments currently
      being developed is its reversibility. Regarding endoscopic anti-reflux therapy in
      general, it is important to stress that at this time no data are available in the
      literature about the comparison to medical therapy. At the same time long-term
      results are also unknown. For these reasons these endoscopic procedures must be
      considered experimental and they should be performed in a clinical research
      setting. Within a few years the role of the Gatekeeper Reflux Repair System will
      be better understood for those PPI-dependent GERD-patients who wish to stop their
      medication.

PMID- 12797438
TI  - Endoscopic implantation of enteryx for the treatment of gastroesophageal reflux
      disease: technique, pre-clinical and clinical experience.
AB  - The implantation of Enteryx polymer in the LES is a fast, minimally invasive
      procedure with anticipated low procedural risks and limited costs. Preliminary
      clinical data after 6 months of follow-up show good results in more than 80% of
      the patients, with objective improvement of acid reflux time. Enteryx is
      effective in the management of GERD, as evidenced by the ability of GERD patients
      with a history of use of PPIs and other GERD medications to eliminate or
      significantly reduce use of these medications. Mechanisms of action of Enteryx
      implantation suggest a change in distensibility of the LES, allowing a greater
      competency of the cardia. LES pressure and length might be increased after
      polymer implantation, and further studies are needed to study the effect of
      Enteryx on transient relaxations of the LES, which is the prevalent mechanism of
      reflux in patients with mild GERD. Challenges with this procedure include
      refining technique to deliver adequate volume in each patient and determining if
      the ring-shaped implant is needed. In addition to acid reflux, another indication
      for use of this treatment might be biliary reflux in gastrectomized patients;
      preliminary data suggest that Enteryx may reduce symptoms and improve bile reflux
      (J. Deviere, unpublished observations, 2002). Further studies are needed to
      definitively establish the safety of the procedure. This is a major point because
      gastroenterologists are not dealing with ill patients but primarily with
      individuals who have a good quality of life while taking PPIs. The other area to
      investigate is the efficacy of the treatment through a sham-controlled study.
      Finally, this endoscopic technique will have to be evaluated in terms of cost
      effectiveness against medical and surgical therapies.

PMID- 12797439
TI  - Endoscopic therapy for gastroesophageal reflux disease: what have we learned and
      what needs to be done?
AB  - GERD is a common, morbid, and expensive-to-treat disease. Clinicians have a
      clearly defined "therapeutic bar" for the efficacy of GERD therapy established
      from extensive study of current pharmacologic and surgical therapies. Endoscopic
      therapies for GERD are promising technologies that probably will find clinical
      application in subsets of patients with GERD. Integration of these new endoscopic
      GERD therapies into routine clinical practice requires more information from
      carefully performed and analyzed trials. Issues that still need to be addressed
      include the efficacy of these devices compared with placebo, efficacy compared
      with other endoscopic techniques, and efficacy versus current therapies.
      Addressing these issues requires the performance of well-designed, blinded
      studies using sham techniques and measuring clinically relevant outcomes using
      validated instruments. Once efficacy has been established, durability of response
      needs to be clearly determined. Intensive postmarketing surveillance, device
      registries, and long-term clinical follow-up studies will be able to document
      durability. The effect of retreatment for relapses or suboptimal initial
      treatment response should also be determined. Safety can best be established with
      extensive postmarketing surveillance and device registries. The impact of formal
      training programs on decreasing the learning curve and improving outcomes,
      including safety, should also be studied. Finally, the cost-effectiveness of
      these devices has to be determined either by economic models or clinical trials
      measuring actual costs. Despite these seemingly large hurdles, one, if not more,
      of these technologies should meet these criteria and soon be used as an
      effective, durable, safe, and cost-effective treatment option for patients with
      GERD.

PMID- 12797440
TI  - Future opportunities and developments for endoscopic gastroesophageal reflux
      disease therapy.
AB  - Endoscopic treatments for gastroesophageal reflux disease are directed at
      specific targets at the gastroesophageal junction. We explore the limitations and
      challenges of the anatomy, how current methods alter the anatomy and then
      speculate on the direction of future therapies.

PMID- 12797441
TI  - The interaction of immunodeficiency viruses with dendritic cells.
AB  - Dendritic cells (DCs) can influence HIV-1 and SIV pathogenesis and protective
      mechanisms at several levels. First, HIV-1 productively infects select
      populations of DCs in culture, particularly immature DCs derived from blood
      monocytes and skin (Langerhans cells). However, there exist only a few instances
      in which HIV-1- or SIV-infected DCs have been identified in vivo in tissue
      sections. Second, different types of DCs reliably sequester and transmit
      infectious HIV-1 and SIV in culture, setting up a productive infection in T cells
      interacting with the DCs. This stimulation of infection in T cells may explain
      the observation that CD4+ T lymphocytes are the principal cell type observed to
      be infected with HIV-1 in lymphoid tissues in vivo. DCs express a C-type lectin,
      DC-SIGN/CD209, that functions to bind HIV-1 (and other infectious agents) and
      transmit virus to T cells. When transfected into the THP-1 cell line, the
      cytosolic domain of DC-SIGN is needed for HIV-1 sequestration and transmission.
      However, DCs lacking DC-SIGN (Langerhans cells) or expressing very low levels of
      DC-SIGN (rhesus macaque monocyte-derived DCs) may use additional molecules to
      bind and transmit immunodeficiency viruses to T cells. Third, DCs are efficient
      antigen-presenting cells for HIV-1 and SIV antigens. Infection with several
      recombinant viral vectors as well as attenuated virus is followed by antigen
      presentation to CD4+ and CD8+ T cells. An intriguing pathway that is well
      developed in DCs is the exogenous pathway for nonreplicating viral antigens to be
      presented on class I MHC products. This should allow DCs to stimulate CD8+ T
      cells after uptake of antibody-coated HIV-1 and dying infected T cells. It has
      been proposed that DCs, in addition to expanding effector helper and killer T
      cells, induce tolerance through T cell deletion and suppressor T cell formation,
      but this must be evaluated directly. Fourth, DCs are likely to be valuable in
      improving vaccine design. Increasing DC uptake of a vaccine, as well as
      increasing their numbers and maturation, should enhance efficacy. However, DCs
      can also capture antigens from other cells that are initially transduced with a
      DNA vaccine or a recombinant viral vector. The interaction of HIV-1 and SIV with
      DCs is therefore intricate but pertinent to understanding how these viruses
      disrupt immune function and elicit immune responses.

PMID- 12797443
TI  - Contrasting roles of dendritic cells and B cells in the immune control of Epstein
      Barr virus.
AB  - The human gamma-herpesvirus, Epstein-Barr virus (EBV), has growth-transforming
      potential in vivo and in vitro. Despite this, most healthy carriers remain free
      of EBV-associated malignancies because of effective T cell-mediated immune
      control of the virus. A better understanding of these highly efficient control
      mechanisms is important in the development of new treatment strategies for EBV
      associated malignancies. A rational approach to EBV immunotherapy requires
      answering two questions about the initiation of the protective EBV-specific
      immune response. The first question is, what is the antigen-presenting cell
      responsible for priming EBV specific immunity? Second, which viral antigen is
      central to protective EBV adaptive immunity seen in healthy carriers of the
      virus? We provide evidence in this review that dendritic cells rather than EBV
      transformed B cells are responsible for orchestrating protective EBV immunity and
      that the EBV nuclear antigen 1 (EBNA1)-specific CD4+ T cell response probably
      plays a role in resistance against all types of EBV-associated malignancies in
      healthy carriers. This implies that EBNA1 targeting to dendritic cells should be
      a component of vaccine and immunotherapy development against EBV-associated
      malignancies.

PMID- 12797442
TI  - DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission.
AB  - The dendritic cell (DC)-specific HIV-1 receptor DC-SIGN plays a key-role in the
      dissemination of HIV-1 by DCs. DC-SIGN captures HIV-1 at sites of entry, enabling
      its transport to lymphoid tissues, where DC-SIGN efficiently transmits low
      amounts of HIV-1 to T cells. The expression pattern of DC-SIGN in mucosal tissue,
      lymph nodes, placenta and blood suggests a function for DC-SIGN in both
      horizontal and vertical transmission of HIV-1. Moreover, the efficiency of DC
      SIGN+ blood DC to transmit HIV-1 to T cells supports a role in HIV-1 transmission
      via blood. To date, DC-SIGN represents a novel class of HIV-1 receptor, because
      it does not allow viral infection but binds HIV-1 and enhances its infection of T
      cells in trans. Its unique function is further underscored by its restricted
      expression on DCs. Although DC-SIGN is a C-type lectin with an affinity for
      carbohydrates exemplified by its interaction with its immunological ligand ICAM
      3, recent evidence demonstrates that glycosylation of gp120 is not necessary for
      its interaction with DC-SIGN. Moreover, mutational analysis demonstrates that the
      HIV-1 gp120 binding site in DC-SIGN is different from that of ICAM-3. Besides its
      role in DC-mediated adhesion processes, DC-SIGN also functions as an antigen
      receptor that captures and internalises antigens for presentation by DC.
      Strikingly, HIV-1 circumvents processing after binding DC-SIGN and remains
      infectious for several days after capture. A better understanding of the action
      of this novel HIV receptor in initial viral infection and subsequent transmission
      will provide a basis for the design of drugs that inhibit or alter interactions
      of DC-SIGN with gp120, interfering with HIV-1 dissemination and that may have a
      therapeutic value in both immunological diseases and/or HIV-1 infections.

PMID- 12797444
TI  - Dendritic cells and measles virus infection.
AB  - Measles is a major cause of childhood mortality in developing countries which is
      mainly attributed to the ability of measles virus (MV) to suppress general immune
      responses. Paradoxically, virus-specific immunity is efficiently induced, which
      leads to viral clearance from the host and confers long-lasting protection
      against reinfection. As sensitisers of pathogen encounter and instructors of the
      adaptive immune response, dendritic cells (DCs) may play a decisive role in the
      induction and quality of the MV-specific immune activation. The ability of MV
      wild-type strains in particular to infect DCs in vitro is dearly established, and
      the receptor binding haemagglutinin protein of these viruses essentially
      determines this particular tropism. DC maturation as induced early after MV
      infection is likely to be of crucial importance for the induction of MV-specific
      immunity. DCs may, however, be instrumental in MV-induced immunosuppression. (1)
      T cell depletion could be brought about by DC-T cell fusion or TRAIL-mediated
      induction of apoptosis. (2) Inhibition of stimulated IL-12 production from MV
      infected DCs might affect T cell responses in qualitative terms in favouring Th2
      and suppressing Th1 responses. (3) The viral glycoprotein complex expressed at
      high levels on infected DCs late in infection is able to directly inhibit T cell
      proliferation by surface contact-dependent negative signalling. This most likely
      accounts for the failure of infected DC cultures to stimulate allogeneic and
      inhibit mitogen-stimulated T cell proliferation in vitro and the pronounced
      proliferative unresponsiveness of T cell ex vivo to polyclonal and antigen
      specific stimulation which is a central finding of MV-induced immunosuppression.

PMID- 12797445
TI  - Measles virus and dendritic cell functions: how specific response cohabits with
      immunosuppression.
AB  - Measles virus (MV) infection induces both an efficient MV-specific immune
      response and a transient but profound immunosuppression characterised by a
      panlymphopenia that occasionally results in opportunistic infections responsible
      for a high rate of mortality in children. On the basis of in vitro studies, the
      putative roles of dendritic cells (DCs) in MV infection are discussed. (1) DCs
      could participate in anti-MV innate immunity because MV turns on TNF-related
      apoptosis-inducing ligand (TRAIL)-mediated DC cytotoxicity. (2) Cross-priming by
      non-infected DCs might be the route of MV adaptive immune response. (3) After
      CD40-ligand activation in secondary lymphoid organs, MV-infected DCs could
      initiate the formation of Warthin-Finkeldey multinucleated giant cells,
      replicating MV and responsible for in vivo spreading of MV. (4) We review how
      integrated viral attack of the host immune system also targets DCs: Progress in
      understanding the immunobiology of MV-infected DCs that could account for MV
      induced immunosuppression observed in vivo is presented and their potential role
      in lymphopenia is underlined. In conclusion, future research directions are
      proposed.

PMID- 12797447
TI  - The interaction between dendritic cells and herpes simplex virus-1.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells, because they
      are also able to induce native T cells. Thus they are crucial in the induction of
      antiviral immune responses. Several viral immune escape mechanisms have been
      described; here we concentrate on the interaction between DCs and herpes simplex
      virus type 1 (HSV-1). DCs can be infected by HSV-1; however, only immature DCs
      generate infectious viral particles, whereas mature DCs do not support virus
      production and only immediate-early and early viral transcripts are generated. To
      induce potent immune responses DCs must mature. Interestingly, HSV-1 interferes
      with this maturation process, thus inhibiting antiviral T cell stimulation.
      Furthermore, HSV-1 strongly interferes with DC-mediated T cell proliferation. A
      striking finding was the complete degradation of CD83, the best-known marker for
      mature DC, after HSV-1 infection in lysosomal compartments. This CD83 degradation
      coincided with a clearly reduced T cell stimulation representing an additional
      new escape strategy. The functional role and the importance of CD83 are discussed
      in detail.

PMID- 12797446
TI  - Infection of dendritic cells by lymphocytic choriomeningitis virus.
AB  - Dendritic cells (DCs) comprise the major antigen-presenting cells (APCs) of the
      host, uniquely programmed to stimulate immunologically naive T lymphocytes.
      Viruses that can target and disorder the function of these cells enjoy a
      selective advantage. The cellular receptor for lymphocytic choriomeningitis virus
      (LCMV), Lassa fever virus (LFV), and several other arenaviruses is alpha
      dystroglycan (alpha-DG). Among cells of the immune system, CD11c+ and DEC-205+
      DCs primarily and preferentially express alpha-DG. By selection, strains and
      variants of LCMV generated as quasi-species that bind alpha-DG with high affinity
      replicate in the majority of CD11c+ and DEC-205+ (>75%) DCs, causing a
      generalized immunosuppression, and establish a persistent infection. In contrast,
      viral strains and variants that bind with low affinity to alpha-DG display
      minimal replication in CD11c+ and DEC-205+ DCs (<10%), rarely replicate in the
      white pulp, and generate a robust anti-LCMV CTL response that clears the virus
      infection. Hence, receptor-virus interaction on DCs in vivo is an essential step
      in the initiation of virus-induced immunosuppression and viral persistence.
      Investigation into the mechanism of how virus-infected DCs cause
      immunosuppression reveals loss of MHC class II surface expression and
      costimulatory molecules on surface of such DCs. As a consequence DCs are unable
      to act as APCs, initiate immune responses, and have a defect in migration into
      the T cell area. These data indicate that LCMV infection influences DC maturation
      and migration, leading to decreased T cell stimulatory capacity of DCs, events
      essential for the initiation of immune responses. Because several other viruses
      known to cause immunosuppression (HIV, measles) interact with DCs, the
      observations noted here are likely a common selective mechanism by which viruses
      also are able to evade the host's immune system.

PMID- 12797448
TI  - Dendritic cell-based immunotherapy.
AB  - Dendritic cell (DC)-based vaccinations represent a promising approach for the
      immunotherapy of cancer and infectious diseases as DCs play an essential role in
      initiating cellular immune responses. A number of clinical trials using ex vivo
      generated DCs have been performed so far and only minor toxicity has been
      reported. Both the induction of antigen-specific T cells and clinical responses
      have been observed in vaccinated cancer patients. Nevertheless, DC-based
      immunotherapy is still in its infancy and there are many issues to be addressed
      such as antigen loading procedures, DC source and maturational state, migration
      properties, route, frequency, and dosage of DC vaccination. The increasing
      knowledge of DC biology should be used to improve the efficacy of this new
      therapy.

PMID- 12797449
TI  - Dendritic cell vaccination and viral infection--animal models.
AB  - Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of
      immune responses against viruses and other microbial pathogens. Adoptively
      transferred, in vitro manipulated DCs presenting antigen derived from different
      viruses have been shown to elicit cytotoxic T cell (CTL) and T helper (Th) cell
      responses and to induce protective antiviral immunity. Furthermore, DC-based
      adoptive immunotherapies have the potential to specifically (re)activate
      antiviral immunity in chronic viral diseases such as HIV or hepatitis virus
      infections. Cellular dendritic cell vaccines, however, are not suitable for large
      scale prophylactic immunization. Strategies for vaccine development should
      therefore aim at the specific delivery of microbial antigens to DCs in situ.
      Furthermore, appropriate mobilization and activation of DCs by the vaccine is
      important for the generation of optimal antimicrobial immune responses. Here, we
      discuss recent data on induction of antiviral immunity with various DC
      vaccination approaches and outline future directions for the development of
      specific antigen targeting to DCs.

PMID- 12797450
TI  - Interplay between human papillomaviruses and dendritic cells.
AB  - The design of the human papillomavirus (HPV) infection cycle is tightly fitted to
      the differentiation program of its natural host, the keratinocyte. This has
      important consequences for the role of antigen-presenting cells in the priming of
      antiviral immunity. The confinement of HPV infection to epithelia puts the
      epithelial dendritic cell, the Langerhans cell (LC), in charge of the induction
      of T cell-dependent immunity. Because HPV-infected keratinocytes cannot reach the
      regional lymphoid organs, and HPV-infection of LCs does not result in viral gene
      expression, priming of antiviral T cells exclusively depends on cross
      presentation of viral antigens by the LC. Sensitization of the immune system in
      the regional lymphoid organs elicits systemic anti-HPV immunity as well as
      intraepithelial immune surveillance by memory-type intraepithelial T cells and
      locally produced antibodies. The high rate of spontaneous rejections of high-risk
      HPV-infections and HPV-positive premalignant lesions indicates that in general
      the LC-driven antigen presentation machinery is capable of raising an effective
      immune defense against HPV. Epidemiological studies also reveal that a decrease
      in the vigilance of the immune system is readily exploited by HPV to escape
      immune destruction, resulting in persistent infections and development of HPV
      positive cancers. In view of the inherent antigenicity of HPV, immune
      intervention strategies constitute a promising approach for both the prevention
      and the therapeutic treatment of HPV-induced diseases. Importantly, the
      mechanisms that govern the induction and effector phases of the intraepithelial
      immune surveillance against HPV must be taken into account when designing such
      strategies.

PMID- 12797451
TI  - Viral vectors for dendritic cell-based immunotherapy.
AB  - Dendritic cells (DCs) constitute a specialised system of antigen-presenting cells
      with a high capacity to induce and to modulate the immune response against
      microbial, tumour and self-antigens. New techniques to generate large amounts of
      DCs together with the molecular identification of human tumour-associated
      antigens (TAA) have opened new ways for antigen-specific cancer immunotherapies.
      DCs loaded either with TAA-derived MHC class I-specific synthetic peptides or
      with whole tumour cell preparations have been used in numerous clinical trials
      evaluating the efficacy of DCs in patients with cancer. However, the
      disadvantages of DCs pulsed with synthetic peptides from TAA include the
      uncertainty regarding the longevity of antigen presentation, the restriction by
      the patient's haplotype and the relatively low number of known MHC class I and in
      particular of MHC class II helper cell-related epitopes. Whole tumour cell
      preparations are difficult to standardise, and they depend on the availability of
      tumour cells. Thus the utilisation of viral vectors genetically modified to
      express TAA for the ex vivo transduction of DCs is an attractive alternative to
      achieve a MHC I- and MHC II-restricted presentation of tumoural antigens. To
      induce protective anti-tumoural immune response an increasing number of modified
      viral vectors have been used to transduce DCs. Although high transduction
      efficacies were reported for several viruses, analysis of the interaction of
      viral vectors with DCs has revealed several viral mechanisms that interfere with
      main functions of DCs, dampening somewhat the initial optimism in the field of DC
      transduction. However, promising results with different vectors have been
      achieved. In this review we summarise available data and discuss advantages and
      drawbacks of currently available vectors.

PMID- 12797452
TI  - Cross-presentation of cell-associated antigens by dendritic cells.
AB  - There is a strict requirement for professional antigen-presenting cells (APCs) in
      the generation of immunity toward most viruses. Exogenous pathways of MHC class I
      restricted antigen presentation play an important role in the generation of
      antiviral immunity, particularly in the immune surveillance of virus-infected
      tissues of nonhematopoietic origin, and to bypass the detrimental effects of
      direct virus infection on professional APCs. The mechanisms underlying generation
      of antiviral immunity under these circumstances are discussed.

PMID- 12797453
TI  - Dendritic cells and HCMV cross-presentation.
AB  - The outcome of a viral infection is the result of an endless fight between the
      organism whose task is to mount an antiviral response and the virus that adapts
      strategies to circumvent the host response. Human cytomegalovirus (HCMV), a
      latent herpesvirus, can be considered as a spearhead in exploiting co-existence
      with the host to develop numerous immuno-evasion mechanisms. The ability of the
      organism to initiate a primary immune response against viruses such as HCMV is
      highly dependent on the capacity of professional antigen-presenting cells (APCs),
      namely dendritic cells (DCs), to prime and activate specific effector T cells.
      Recent findings emerging from the murine cytomegalovirus (MCMV) animal model
      demonstrated that infection of murine DCs with MCMV impaired their capacity to
      prime an effective T cell response. Even though data on interference of HCMV with
      DC functions are still limited, immunosuppressive effects identical to those
      reported for MCMV can be suspected and we may then ask how a cytotoxic T
      lymphocyte (CTL) response is generated in these unfavourable conditions. In
      response to this question, cross-presentation of HCMV antigens by uninfected DCs
      to CD8+ T cells could be considered a key process in initiating an immune
      response. In this chapter we discuss the mechanisms through which DCs could
      acquire HCMV antigens and how cross-presentation could be modulated throughout
      infection. Moreover, further knowledge of DC functions is key for the development
      of DC-based immunotherapy against HCMV.

PMID- 12797454
TI  - Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome: postulated
      involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly
      or heterotaxia.
AB  - BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due
      to an inborn error of cholesterol metabolism and is characterized by
      developmental delay, facial anomalies, hypospadias, congenital heart defect
      (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the
      propositi, and a specific association with atrioventricular canal defect (AVCD)
      and anomalous pulmonary venous return has been demonstrated. METHODS: We report
      on an additional patient with RSH/SLOS presenting with complete AVCD and
      anomalous pulmonary venous return, and discuss the possible relationship of the
      Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in
      heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic
      similarities between heterotaxia and CHDs of several syndromes with postaxial
      polydactyly have been noted previously, considering the frequent association of
      AVCD with common atrium in these conditions. It is known that both CHDs of
      heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH
      pathway. Cholesterol has a critical role in the formation of normally active
      hedgehog proteins. It could be hypothesized that specific types of CHDs in
      RSH/SLOS can be caused by modifications of the SHH protein related to the defect
      of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and
      anomalous pulmonary venous return in patients with RSH/SLOS and the finding of
      AVCD +/- common atrium in several syndromes with polydactyly leads to the
      hypothesis that heterotaxia due to SHH anomalies could be involved in a large
      spectrum of conditions. Perturbations in different components of the SHH pathway
      could lead to several developmental errors presenting with partially overlapping
      clinical manifestations.

PMID- 12797455
TI  - Evaluation of infant methylenetetrahydrofolate reductase genotype, maternal
      vitamin use, and risk of high versus low level spina bifida defects.
AB  - BACKGROUND: Several studies have suggested that homozygosity for the C677T 5,10
      methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor
      for neural tube defects (NTDs), as individuals homozygous for the C677T allele
      have slightly elevated homocysteine concentrations under conditions of low folic
      acid intake. It has been hypothesized that maternal folic acid supplementation
      prevents NTDs by partially correcting reduced MTHFR activity associated with the
      variant form of the enzyme. METHODS: Genomic DNA was extracted from newborn
      screening blood spots obtained from 145 infants with spina bifida (SB) and 260
      nonmalformed control infants. The MTHFR C677T genotype was determined by
      restriction enzyme digestion of PCR amplification products with Hinf1. We
      investigated whether infant MTHFR genotype influenced the risk for the anatomic
      level of the SB lesion (high vs. low); we also explored whether maternal vitamin
      use influenced this risk. RESULTS: Compared to controls, the frequency of SB
      infants with the homozygous 677 TT genotype was greatest in those infants with
      high level SB defects (26%; odds ratio [OR] = 2.9; 95% confidence interval [CI] =
      0.9-10.1) than for those with low level SB defects (22%; OR = 1.8; 95% CI = 0.9
      3.2). Furthermore, homozygous 677TT infants whose mothers did not use vitamins
      containing folic acid had a modestly increased risk of SB (OR = 1.8; 95% CI = 0.8
      3.9), with this risk increasing more than three-fold (OR = 5.5; 95% CI = 0.8
      28.1) for those infants with high level SB defects whose mothers did not use
      vitamins. CONCLUSIONS: Based upon our observations, it is suggested that the
      association between the infant MTHFR homozygous variant genotype and spina bifida
      risk may be conditional upon both lesion level and maternal vitamin use.

PMID- 12797456
TI  - Risk factors for neural tube defects: associations between uncoupling protein 2
      polymorphisms and spina bifida.
AB  - BACKGROUND: Polymorphisms in the mitochondrial membrane transporter gene UCP2 are
      capable of affecting energy metabolism, body weight regulation, and possibly
      preventing the buildup of reactive oxygen species, all factors that could
      contribute to neural tube defect risk through maternal obesity and diabetes.
      METHODS: Genomic DNA was extracted from newborn screening blood spots obtained
      from infants with spina bifida and nonmalformed control infants. Genotype
      frequencies of two genetic variants in the UCP2 gene, an amino acid substitution
      of valine for alanine at codon 55 in exon 4, and a 45-base pair
      insertion/deletion in the 3' untranslated region of exon 8,were determined by
      restriction enzyme digestion of PCR amplification products. RESULTS: We found the
      frequency of the 3' untranslated region deletion homozygous genotype (256/256) as
      well as the A55V homozygous (Val/Val) genotype to be higher in SB infants than in
      controls (odds ratio [OR], 3.1; 95% confidence interval [CI], 0.9-10.4 and OR =
      2.0; 95% CI = 0.3-11.1, respectively). Additionally, the frequency of the
      combined homozygous 256/256,+ / + genotype was higher in cases and resulted in
      more than a threefold higher spina bifida risk (OR = 3.6; 95% CI = 1.0-13.1).
      CONCLUSIONS: These data are the first to suggest that polymorphisms in the UCP2
      gene may be genetic risk factors of spina bifida.

PMID- 12797457
TI  - Population-based study of l-transposition of the great arteries: possible
      associations with environmental factors.
AB  - BACKGROUND: L-transposition of the great arteries (l-tga) is an uncommon
      congenital cardiovascular malformation that occurs from abnormal looping of the
      primitive cardiac tube. Little is known about risk factors for the development of
      l-tga. METHODS: This study is a case-control study of 36 cases of l-tga compared
      to 3,495 population-based live born infant controls in the Baltimore Washington
      Infant Study (1981-1989 births). Extensive personal and occupational exposure
      data from parental interviews were available for all subjects. A geographic
      information system was used to identify potential environmental exposures, for
      example, hazardous waste sites prioritized for cleanup (National Priority List
      sites). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were
      calculated using exact parameter estimates from logistic regression. RESULTS:
      Most infants with l-tga had multiple cardiovascular anomalies, with single
      ventricle in 47%. Over 75% of all cases of l-tga occur in two regions of
      contiguous cases. Within these regions, the case control OR of l-tga are 13.4
      (95% CI, 4.7-37.8) Both areas are characterized by release of toxic chemicals
      into air and by hazardous waste sites. Parental exposures to hair dye, smoking
      and laboratory chemicals are also associated with case status. CONCLUSIONS: L
      tga, a congenital cardiovascular malformation due to very early abnormalities in
      embryogenesis, is associated strongly with residency in two small regions of
      Maryland and District of Columbia (DC), and with other parental personal or
      occupational exposures. Additional research is needed to identify the components
      of spatial and other associations that constitute etiologic risk factors.

PMID- 12797458
TI  - Combination therapy with folic acid and methionine in the prevention of retinoic
      acid-induced cleft palate in mice.
AB  - BACKGROUND: During formation of the secondary palate, clefting may result when
      critical developmental events are altered. The purpose of this study was to
      reduce the incidence of retinoic acid (RA)-induced cleft palate (CP) in mice by
      the co-administration of folic acid (FA), methionine (ME) or a combination of
      both. METHODS: Four groups of time-pregnant Swiss Webster mice were injected
      intraperitoneally with 50 mg/kg RA on gestational day (GD) 10. Likewise, 4.0
      mg/kg FA and 187 mg/kg ME were administered on GD 8-11. The experiment included a
      control group (RA plus H2O) and three experimental groups, (RA plus therapeutic
      doses of FA, ME, or FA + ME). Necropsies were carried out on GD 18 and pups were
      analyzed for teratogenic effects. RESULTS: Litters that received no therapy
      exhibited 100% CP with individual pups showing 76% susceptibility. Each therapy
      administered separately reduced the frequency of CP to approximately 6%, and the
      combination of FA and ME completely prevented the occurrence of RA-induced cleft
      palate (0%). A second experiment was conducted in which therapy levels were
      decreased by 25%. Litters that did not receive therapy experienced 100% clefting
      and individual pups exhibited CP at 86%. These therapies administered separately
      did not alter significantly the frequency of cleft palate. The combined doses of
      FA and ME, however, lowered significantly the frequency of cleft palate to 46%.
      Decreases in limb and tail defects with FA + ME therapy were also observed in
      both experiments. CONCLUSIONS: Although FA and ME, at appropriate levels, can
      reduce individually the frequency of RA-induced cleft palate and other defects in
      mice, the results from the present study suggest that there is an additive
      interaction between the two therapeutic agents that can reduce further the
      teratogenic impact of RA. Further studies are needed to assess the mechanism of
      action of concomitant doses of FA and ME in the reduction of drug-induced birth
      defects.

PMID- 12797459
TI  - Anticonvulsant valproic acid inhibits cardiomyocyte differentiation of embryonic
      stem cells by increasing intracellular levels of reactive oxygen species.
AB  - BACKGROUND: The anticonvulsant valproic acid (VPA) exerts teratogenic properties
      and has been demonstrated to cause neural tube defects and malformations of the
      heart. The effect of VPA on the differentiation of cardiomyocytes from
      pluripotent murine embryonic stem cells (ES cells) was investigated. METHODS:
      Embryoid bodies derived from ES cells were treated with different concentrations
      of VPA and the differentiation of cardiomyocytes was monitored by
      immunohistochemical staining for sarcomeric alpha-actinin. Cytotoxicity was
      evaluated by the use of the dead cell stain SYTOX green. Intracellular levels of
      reactive oxygen species (ROS) within the tissue were evaluated by the use of the
      redox-sensitive dye dichlorodihydrofluorescein diacetate (H2DCFDA). RESULTS: VPA
      retarded the growth of ES cell-derived embryoid bodies but did not exert
      cytotoxic effects. The compound dose-dependently inhibited the development of
      spontaneously beating clusters of cardiomyocytes within embryoid bodies grown
      from ES cells and reduced the extension of beating areas of cardiac cells.
      Furthermore, VPA significantly increased ROS levels, indicating that VPA altered
      the intracellular redox balance. To investigate whether the inhibition of
      cardiomyocyte differentiation by VPA was owing to increased ROS overwhelming the
      intracellular antioxidative defense, the compound was coadministered with the
      free radical scavenger vitamin E. CONCLUSIONS: This treatment significantly
      restored cardiomyogenic differentiation, indicating that VPA inhibits
      cardiomyogenesis of ES cells by increasing intracellular ROS levels.

PMID- 12797460
TI  - Atenolol developmental toxicity: animal-to-human comparisons.
AB  - BACKGROUND: Atenolol, 4-2'-hydroxy-3'-isopropyl-aminopropoxy) phenylacetamide, is
      a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy.
      Beta-blockers are reported to cause fetal harm (such as decreased birth weight)
      when administered to a pregnant woman. We evaluate published human and animal
      evidence of atenolol developmental toxicity and compare the manifestations in
      humans and in routinely-used animal models. METHODS: The comparison is based on
      the following criteria: comparability of pharmacokinetic/pharmacodynamic
      characteristics, type of adverse outcome, lowest adverse effect levels, and
      specificity and selectivity of effect. RESULTS: Manifestations of atenolol
      prenatal toxicity (placental changes, intrauterine growth retardation and changes
      in fetal weight in the absence of structural malformations) are similar in the
      tested animal species (rats and rabbits) and humans. The human seems to be more
      sensitive, however, because adverse embryo-fetal effects are reported at doses
      much lower than those in the tested species. In humans and rats, adverse embryo
      fetal effects are induced by doses that are not maternally toxic. In the rabbit,
      however, such effects are seen only at maternally toxic doses, suggesting that in
      this species, developmental toxicity may be maternally mediated. CONCLUSIONS: The
      available data suggest animal-human concordance with regard to the nature and
      manifestations of atenolol prenatal toxicity. The animal models "predicted"
      developmental toxicity manifests as placental changes, intrauterine growth
      retardation and fetal weight decrease in the absence of structural malformations.
      Thus far, this is concordant with the data from humans, in whom intrauterine
      growth retardation has been observed but not structural abnormalities.

PMID- 12797461
TI  - Guidelines for case classification for the National Birth Defects Prevention
      Study.
AB  - BACKGROUND: Previous studies have suggested that etiologic heterogeneity may
      complicate epidemiologic analyses designed to identify risk factors for birth
      defects. Case classification uses knowledge of embryologic and pathogenetic
      mechanisms to make case groups more homogeneous and is important to the success
      of birth defects studies. METHODS: The goal of the National Birth Defects
      Prevention Study (NBDPS), an ongoing multi-site case-control study, is to
      identify environmental and genetic risk factors for birth defects. Information on
      environmental risk factors is collected through an hour-long maternal interview,
      and DNA is collected from the infant and both parents for evaluation of genetic
      risk factors. Clinical data on infants are reviewed by clinical geneticists to
      ensure they meet the detailed case definitions developed specifically for the
      study. To standardize the methods of case classification for the study, an
      algorithm has been developed to guide NBDPS clinical geneticists in this process.
      RESULTS: Methods for case classification into isolated, multiple, and syndrome
      categories are described. Defects considered minor for the purposes of case
      classification are defined. Differences in the approach to case classification
      for studies of specific defects and of specific exposures are noted. CONCLUSIONS:
      The case classification schema developed for the NBDPS may be of value to other
      clinicians working on epidemiologic studies of birth defects etiology.
      Consideration of these guidelines will lead to more comparable case groups, an
      important element of careful studies aimed at identifying risk factors for birth
      defects.

PMID- 12797462
TI  - Association of congenital malalignment of the nail and a constricting band of a
      digit.

PMID- 12797463
TI  - No effects of bisphosphonates on the human fetus.

PMID- 12797464
TI  - Rare neurologic injury from amniocentesis.

PMID- 12797465
TI  - Classification of drugs for teratogenic risk: an anachronistic way of counseling:
      a reply to Merlob And Stahl.

PMID- 12797466
TI  - The role of oxidative stress in diabetic vascular and neural disease.
AB  - This review will focus on the impact of hyperglycemia-induced oxidative stress in
      the development of diabetes-induced vascular and neural dysfunction. Oxidative
      stress occurs when the balance between the production of oxidation products and
      the ability of antioxidant mechanisms to neutralize these products is tilted in
      the favor of the former. The production of reactive oxygen species has been shown
      to be increased in patients with diabetes. The possible sources for the
      overproduction of reactive oxygen species is widespread and include enzymatic
      pathways, autoxidation of glucose and the mitochondria. Increase in oxidative
      stress has clearly been shown to contribute to the pathology of vascular disease
      not only in diabetes but also in hypertension, stroke and ischemia. Since the
      etiology of diabetic neuropathy is considered to have a large vascular component,
      prevention of oxidative stress in diabetes is considered by many investigators to
      be a primary defense against the development of diabetic vascular disease.
      Potential therapies for preventing increased oxidative stress in diabetes and the
      neural vasculature will be discussed.

PMID- 12797467
TI  - Myeloperoxidase has directly-opposed effects on nitration reaction--study on
      myeloperoxidase-deficient patient and myeloperoxidase-knockout mice.
AB  - Myeloperoxidase (MPO) catalyzes a nitration reaction to form nitrotyrosine in the
      presence of high nitrite, the metabolite of NO. Human leukocyte was shown to
      cause phenolic nitration using released MPO as a catalyst in the presence of
      nitrite. It opposes our previous finding that inhibition of MPO was essential for
      phenol nitration in human leukocyte study. To clarify the role of MPO, we
      utilized MPO-deficient human leukocytes and MPO-knockout mice. Even in the
      absence of exogenously added nitrite, high nitration product was observed in MPO
      deficient leukocytes. In liver subjected to ischemia/reperfusion injury, a
      significantly higher amount of nitrotyrosine was produced in MPO-knockout mice
      than in normal mice. These results clearly demonstrate that MPO inhibits the
      accumulation of nitration products in vivo. Further experiments showed that MPO
      could degrade nitrotyrosine in the presence of glutathione. Thus, MPO-induced
      degradation of nitration products may cause the underestimation of the nitration
      product generated in vivo. We conclude that MPO may act predominantly to scavenge
      nitrotyrosine under physiological nitrite condition, and protect against
      injurious effect of nitrotyrosine.

PMID- 12797468
TI  - 3,4-Methylenedioxymethamphetamine (MDMA) abuse may cause oxidative stress and
      potential free radical damage.
AB  - OBJECTIVE: To investigate whether 3,4-methylenedioxymethamphetamine abuse (MDMA
      abuse) may cause oxidative stress and potential free radical damage in the bodies
      of MDMA abusers (MA), and to explore the mechanisms by which MDMA abuse may be
      causing oxidative stress. METHODS: One hundred and twenty MA and 120 healthy
      volunteers (HV) were enrolled in a random control study design, in which the
      level of lipoperoxide (LPO) in erythrocytes, and the levels of Vitamin C (VC),
      Vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as the activities
      of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes were determined
      by spectrophotometric methods. RESULTS: Compared with the average values of the
      above biochemical parameters in the HV group, the average value of LPO in
      erythrocytes in the MA group was significantly increased (P < 0.0001), while the
      average values of VC, VE and beta-CAR in plasma as well as those of SOD and CAT
      in erythrocytes in the MA group were significantly decreased (P < 0.0001). The
      analysis of bivariate correlations suggested that with the increase of the MDMA
      abuse dose and the MDMA abuse duration, the level of LPO in erythrocytes in the
      MA was increased (P < 0.0001), while the levels of VC, VE and beta-CAR in plasma
      as well as the activities of SOD and CAT in erythrocytes in the MA were decreased
      (P < 0.0001). CONCLUSION: The findings in this study suggest that MDMA abuse may
      cause oxidative stress and potential free radical damage to MA.

PMID- 12797469
TI  - Urinary 8-hydroxy-2'-deoxyguanosine, a metabolite of oxidized DNA, is not
      elevated in HIV patients on combination antiretroviral therapy.
AB  - Mitochondrial toxicity of nucleoside analogues has been proposed to be the
      etiology of a range of side-effects from antiretroviral therapy of HIV infection.
      In this study, urinary 8-hydroxy-2'-deoxyguanosine (8OH2'dG), a metabolite of
      oxidized DNA, was measured to determine if antiretroviral therapy leads to
      oxidative damage to DNA. A cross-sectional study was carried out measuring
      urinary 8OH2'dG in three groups of HIV-infected patients: (1) antiretroviral
      medication naive, (2) patients on antiretroviral medications without
      lipodystrophy and (3) patients on antiretroviral medications with lipodystrophy.
      Twenty-five patients were enrolled in each group. The mean spot urinary 8OH2'dG
      measurements per mg creatinine for the three groups were: antiretroviral naive
      4.27 +/- 0.61 (ng 8OH2'dG/mg creatinine +/- SEM), on antiretroviral medications
      without lipodystrophy 2.88 +/- 0.26, and on antiretroviral medications with
      lipodystrophy 3.27 +/- 0.30. The differences between the means of the three
      groups is not statistically significant (p = 0.055), and these results are not
      significantly different from reported values for healthy controls [A carbon
      column-based liquid chromatography electrochemical approach to routine 8-hydroxy
      2-deoxyguanosine measurements in urine and other biologic matrices: a one-year
      evaluation of methods. Free Radical Biology and Medicine 27 (1999) 647-666].

PMID- 12797470
TI  - Taking EPR "snapshots" of the oxidative stress status in human blood.
AB  - Assessment of oxidative stress status (OSS) in human tissues is still
      troublesome. Using an innovative EPR-radical-probe we successfully measured the
      instantaneous concentration of ROS directly in peripheral blood of athletes and
      normally active workers during 60 min controlled exercise. The probe employed was
      bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate, which quantitatively
      and instantaneously reacts with oxygen-centered radicals (including superoxide)
      to yield the parent nitroxide, which is sufficiently persistent to be measured by
      EPR. Our measurements suggest that while at rest normally active individuals may
      benefit more from antioxidant supplementation than athletes; conversely, during
      exercise athletes may benefit more from supplementation. Our method allows
      reliable, quick, and non-invasive quantitative determination of OSS in human
      peripheral blood.

PMID- 12797472
TI  - Effect of aluminium on lipid peroxidation of human high density lipoproteins.
AB  - We investigated the effect of aluminium (Al3+) on lipid peroxidation and physico
      chemical properties of high density lipoproteins (HDL) isolated from human
      plasma. Our results demonstrated that Al3+ enhances lipid peroxidation of human
      HDL as shown by the significant increase in lipid hydroperoxides in Al-treated
      HDL with respect to control HDL. The oxidative effect was higher at acid pH (pH
      5.5) with respect to pH 7.4. Moreover, a stimulating effect of Al3+ on iron
      induced lipid peroxidation of HDL was demonstrated. The study of the effect of
      Al3+ on the physico-chemical properties of HDL, using the fluorescence
      polarization (Pf) of the probes TMA-DPH (1-(4-trimethylammoniumphenyl)-6-phenyl
      1,3,5-hexatriene iodide) and DPH (1,6-diphenyl-1,3,5-hexatriene), showed a
      significant decrease of Pf in Al-treated HDL with respect to control. These
      results suggest that Al3+ induces a decrease of molecular order at the
      lipoprotein surface. Moreover, the study of tryptophan (Trp) fluorescence
      demonstrated that aluminium induces structural modifications of HDL apoproteins
      and on HDL physico-chemical properties. The effect of Al3+ on lipid peroxidation
      of HDL was observed at aluminium concentrations similar to those observed in the
      brain of patients affected by neurological diseases. Aluminium-induced oxidative
      damage of HDL could be involved in the development of neurological diseases.

PMID- 12797471
TI  - Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced
      oxidative DNA damage in human lymphocytes.
AB  - The protective effects of resveratrol and 4-hexylresorcinol against oxidative DNA
      damage in human lymphocytes induced by hydrogen peroxide were investigated.
      Resveratrol and 4-hexylresorcinol showed no cytotoxicity to human lymphocytes at
      the tested concentration (10-100 microM). In addition, DNA damage in human
      lymphocytes induced by H2O2 was inhibited by resveratrol and 4-hexylresorcinol.
      Resveratrol and 4-hexylresorcinol at concentrations of 10-100 microM induced an
      increase in glutathione (GSH) levels in a concentration-dependent manner.
      Moreover, these two compounds also induced activity of glutathione peroxidase
      (GPX) and glutathione reductase (GR). The activity of glutathione-S-transferase
      (GST) in human lymphocytes was induced by resveratrol. Resveratrol and 4
      hexylresorcinol inhibited the activity of catalase (CAT). These data indicate
      that the inhibition of resveratrol and 4-hexylresorcinol on oxidative DNA damage
      in human lymphocytes induced by H2O2 might be attributed to increase levels of
      GSH and modulation of antioxidant enzymes (GPX, GR and GST).

PMID- 12797473
TI  - Free radicals in wheat flour change during storage in air and are influenced by
      the presence of ozone during the growing season.
AB  - Electron paramagnetic resonance (EPR) spectra of wheat flour show components from
      Fe(III), Mn(II) and free radicals (FR). The metal signals were higher in the
      samples from the stressed plants, and reflected the higher total levels of these
      elements determined analytically. They remained essentially constant throughout
      the experiment, but the FR signal increased progressively with time over a period
      of 4-6 months after milling, after which it reached a maximum. The rate of
      increase in the FR signal during this period was considerably higher in the flour
      from plants that had been exposed to elevated ozone levels.

PMID- 12797474
TI  - Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites
      and endogenous NOS inhibitors in hypercholesterolemic subjects.
AB  - Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the
      endogenous inhibitor of NO synthase. The statins have lipid-lowering and
      pleiotropic properties, which could exert protective effects on the endothelium
      in hypercholesterolemia. The association of L-arginine with simvastatin could
      promote a further improvement on endothelial function in this condition. Thus, we
      investigated whether simvastatin, with or without supplementation with L
      arginine, could improve endothelium-dependent vasodilation. In this study, 25
      hypercholesterolemic subjects were treated according to the following protocol:
      washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20
      mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen
      at random for evaluation of vascular function by high resolution ultrasonography
      of the brachial artery. In subjects treated with simvastatin plus L-arginine, an
      increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine
      (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations
      of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%),
      total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the
      LDL-cholesterol/high density lipoprotein (HDL-cholesterol ratio (34%).
      Simvastatin, associated or not to L-arginine, did not affect ADMA levels and
      endothelium-dependent vasodilation. Our data showed that simvastatin reduced the
      plasma concentrations of NOx and RSNO without affecting either the levels of ADMA
      or endothelium-dependent vasodilation in hypercholesterolemia.

PMID- 12797476
TI  - Oxidative damage to catalase induced by peroxyl radicals: functional protection
      by melatonin and other antioxidants.
AB  - Thermal decomposition by the azo initiator 2,2' azobis(2-amidinopropane)
      dihydrochloride (AAPH) has been widely used as a water-soluble source of free
      radical initiators capable of inducing lipid peroxidation and protein damage.
      Here, in a lipid-free system, AAPH alone (40 mM) rapidly induced protein
      modification and inactivation of the enzyme catalase (EC 1.11.1.6). Using SDS
      PAGE, it was shown that protein band intensity is dramatically reduced after 4 h
      of incubation with AAPH, leading to protein aggregation. Several antioxidants
      including melatonin, glutathione (GSH) and trolox prevented catalase modification
      when used at a 250 microM concentration whereas ascorbate was only effective at 1
      mM concentration. All the antioxidants tested reduced carbonyl formation although
      melatonin was the most effective in this regard. Enzyme inactivation caused by
      AAPH was also significantly reduced by the antioxidants and again melatonin was
      more efficient than the other antioxidants used in this study. Results shown here
      demonstrate that alkyl peroxyl radicals inactivate catalase and reduce the
      effectiveness of cells to defend against free radical damage; the damage to
      catalase can be prevented by antioxidants, especially melatonin.

PMID- 12797477
TI  - Antioxidant activity of Baccharis articulata extracts: isolation of a new
      compound with antioxidant activity.
AB  - Baccharis articulata is traditionally used as diuretic and digestive in local
      folk medicine of south of Brazil, Uruguay and Argentina. The antioxidant activity
      of crude ethanol and aqueous extracts, together with ethyl acetate and n-butanol
      fractions obtained from aqueous extract of B. articulata was determined using
      TRAP and TBARS assays. The n-butanol fraction was found to be the most active and
      its major compound (BaII) was isolated, identified and assayed. The structure of
      the phenolic compound BaII was established by means of spectroscopic and chemical
      methods as 4'-O-beta-D-glucopyranosyl-3',5'-dimethoxybenzyl-caffeate. This
      previously unreported metabolite presented similar antioxidant capacity when
      compared to Trolox.

PMID- 12797475
TI  - Thiols are main determinants of total antioxidant capacity of cellular
      homogenates.
AB  - While the total antioxidant capacity (TAC) of blood plasma is mainly accounted
      for by urate, TAC of cell interior can be expected to depend more on other
      antioxidants, especially glutathione and protein -SH groups. We studied TAC of
      homogenates of several lines of cultured cells subjected to the action of thiol
      modifying agents. Comparison of changes of TAC of the homogenates and of the
      level of total thiols (determined with a biradical spin label) demonstrates that
      alterations in cellular thiol content is the main determinant of changes of TAC
      of cell homogenates. These results show that estimation of TAC of cell extracts
      may be a useful parameter of assessment of oxidative stress, primarily of
      oxidation of thiol groups, yielding information different than TAC of body
      fluids.

PMID- 12797478
TI  - Protective activity of (-)-epicatechin 3-O-gallate against peroxynitrite-mediated
      renal damage.
AB  - The protective effect of (-)-epicatechin 3-O-galate (ECg) against peroxynitrite
      (ONOO-)-mediated damage was examined using an animal model and a cell culture
      system. In rats subjected to lipopolysaccharide (LPS) administration plus
      ischemia-reperfusion, the plasma 3-nitrotyrosine level an indicator of ONOO-
      production in vivo, was elevated, whereas it declined significantly and dose
      dependently after the oral administration of ECg at doses of 10 and 20
      micromoles/kg body weight/day for 20 days prior to the process. Moreover, oral
      administration of ECg significantly enhanced the activities of the antioxidant
      enzymes, superoxide dismutase, catalase and glutathione peroxidase, and the
      antioxidant glutathione, showing enhancement of the biological defense system
      against the damage induced by ONOO-. In addition, the significant increase in the
      renal mitochondrial thiobarbituric acid-reactive substance level of LPS and
      ischemic-reperfused control rats was attenuated in rats given ECg. Furthermore,
      the elevations in the plasma urea nitrogen and creatinine (Cr) levels and the
      urinary methylguanidine/Cr ratio induced by the procedure were attenuated
      markedly after oral administration of ECg, implying amelioration of renal
      impairment. The addition of ECg (25 or 125 microM) prior to 3
      morpholinosydnonimine (SIN-1, 800 microM) exposure reduced ONOO- formation and
      increased the viability of cultured renal epithelial (LLC-PK1) cells in a dose
      dependent manner. In particular, ECg inhibited ONOO(-)-mediated apoptotic cell
      death, which was confirmed by decreases in the DNA fragmentation rate and the
      presence of apoptotic morphological changes, i.e. small nuclei and nuclear
      fragmentation. Furthermore, adding ECg before SIN-1 treatment regulated the cell
      cycle by enhancing G2/M phase arrest. This study provides evidence that ECg has
      protective activity against the renal damage induced by excessive ONOO- in
      cellular and in vivo systems.

PMID- 12797480
TI  - Asthma, rhinitis and air pollution: is traffic to blame?

PMID- 12797479
TI  - Grape and grape seed extract capacities at protecting LDL against oxidation
      generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell
      production. A comparison to other extracts or compounds.
AB  - A large body of evidence supports the key role of oxidized low-density
      lipoprotein in atherosclerosis. The aim of this study was to compare the capacity
      of natural polyphenols (PP) from Vitis vinifera and Olea europea at protecting
      LDL against oxidation brought about by Cu2+, oxygen-centered radical-generating
      AAPH, or peroxynitrite-generating SIN-1 in vitro systems, or at impairing
      superoxide production in promonocyte cells (THP-1) conveniently differentiated
      into adherent macrophages. PP were either from the whole grape (fraction A)
      containing mainly procyanidins, (epi)-catechin and anthocyanins, or from grape
      seed extracts (fractions B and C) consisting of tannins and procyanidin oligomers
      with a higher content in B than in C, or from a grape skin extract (fraction D)
      consisting mainly of anthocyanins, or from a hydrosoluble olive mill wastewater
      PP extract (fraction E) containing hydroxytyrosol and oleuropein. Chlorogenic
      acid (F) and catechin (G) were taken as archetypes of PP preventing oxidation
      partly as copper scavenger and as radical scavenger only, respectively. All grape
      fractions were efficient towards Cu2+ system (equally or more efficient than F),
      whereas they were rather poorly efficient towards AAPH and SIN-1 (less efficient
      than G but as efficient as F). Among the PP fractions, B was the most effective
      at protecting LDL in the SIN-1 system and at impairing THP-1 superoxide
      production. Taken together, these data suggest that the PP fraction from grape
      seed rich in procyanidins achieves the best compromise between the direct and
      indirect (i.e. cell-mediated) types of action in protecting LDL against
      oxidation, strengthening the need for improving the knowledge of its
      bioavailability in humans.

PMID- 12797481
TI  - Rescue! Therapy and the paradox of the Barcalounger.

PMID- 12797482
TI  - Endothelial cells modulate eosinophil surface markers and mediator release.
AB  - Migration from blood to tissue modulates eosinophil function, possibly through
      interactions with endothelial cells. The effects of contact with and migration
      through endothelial cells on eosinophil expression of surface markers and release
      of leukotriene C4 were evaluated. A small proportion (2.6%) of eosinophils
      spontaneously migrated through endothelial cell monolayers. Activation of
      endothelial cells by interleukin (IL)-4 or IL-1beta slightly increased this
      migration (to 12.4%), which became much greater when a chemoattractant was placed
      in the lower chamber (84.3%). However, the chemotactic effect was downregulated
      by pretreating endothelial cells with interferon gamma (IFN-gamma; 63.1%). At
      baseline, 5% of eosinophils expressed CD69; this increased to 30.7% in culture on
      untreated endothelial cells and to 50.9% on IL-1beta-pretreated endothelial
      cells. This effect was mediated through intercellular adhesion molecule-1/CD11b
      interaction. Eosinophil migration through endothelial cells further increased
      CD69 expression to 63.9% and also increased CD35 expression from 83.3 to 91.3%.
      Upon stimulation, eosinophils that had migrated through endothelial cells
      produced more leukotriene C4 than control cells (872.4 and 103.9 pg x mL(-1),
      respectively). Endothelial cell pretreatment with IL-4 or IL-1beta further
      increased leukotriene C4 release (1,789.1 and 2,895.1 pg x mL(-1), respectively),
      whereas pretreatment with IFN-gamma decreased it (293.7 pg x mL(-1)). These data
      show that in vitro interactions with endothelial cells upregulate eosinophil
      membrane receptor expression and mediator release and that these effects are
      differently modulated by T-helper cell type 1 and 2 cytokines. These eosinophil
      modulations may play an important role in asthma pathogenesis.

PMID- 12797483
TI  - Upregulated response to chemokines in oxidative metabolism of eosinophils in
      asthma and allergic rhinitis.
AB  - Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage
      in allergic inflammation. CC chemokines, especially eotaxin and regulated on
      activation, normal T-cell expressed and secreted (RANTES), are involved not only
      in chemotaxis but also in eosinophil activation, such as ROS production. It has
      been shown that eosinophils from allergic patients are not functionally
      equivalent to those from normal subjects. In the present study, the
      characteristics of chemokine-primed ROS production in eosinophils from allergic
      patients and normal controls were compared. After pretreatment with chemokines,
      eosinophils were stimulated with calcium ionophore A23187. ROS production by
      eosinophils was measured using luminol-dependent chemiluminescence. Both RANTES
      and eotaxin exhibited a priming effect on calcium ionophore-induced ROS
      production from eosinophils. Despite there being no difference in expression of
      CC chemokine receptor 3, the priming effect of RANTES and eotaxin was
      significantly enhanced in eosinophils from the patients. Interleukin-5 further
      enhanced the priming effect of chemokines in eosinophils from normal subjects,
      but not those from allergic subjects. The present results suggest an upregulated
      response to chemokines in eosinophils from allergic patients, and that
      interleukin-5 can induce a similar phenotype to that found in vivo in allergic
      patients.

PMID- 12797484
TI  - Pseudomonas aeruginosa adherence to human basement membrane collagen in vitro.
AB  - The mechanisms for Pseudomonas aeruginosa colonisation in the airways of patients
      with bronchiectasis and cystic fibrosis are poorly understood. P. aeruginosa
      could evade mucociliary clearance by adhering to the basement membrane at areas
      denuded of intact respiratory epithelium. The authors have developed an in vitro
      model to study P. aeruginosa adherence to human basement membrane type-IV
      collagen by using scanning electron microscopy. P. aeruginosa adherence density
      was determined as the number of P. aeruginosa per 20 microscope fields (2,000x)
      to log inocular size after incubation at 37 degrees C for 45 min. The presence of
      phytohaemagglutinin (PHA)-E, which binds specifically to D-galactose-beta1-4-D-N
      acetylglucosamine, significantly reduced P. aeruginosa adherence density compared
      with control. The presence of heparin and calcium also significantly reduced P.
      aeruginosa adherence density. P. aeruginosa adherence was not affected by the
      presence of proline, trans-hydroxyproline, glycine, galactose, N-acetylneuraminic
      acid, N-acetylglucosamine or Arachis hypogea. Pseudomonas aeruginosa adherence
      probably acts via recognition of the D-galactose-beta1-4-D-N-acetylglucosamine
      sequence on type-IV collagen and this process could be inhibited by heparin and
      calcium. As persistent Pseudomonas aeruginosa colonisation is detrimental to
      patients with cystic fibrosis and bronchiectasis and there is currently no
      effective treatment for its eradication, these results could lead to novel
      therapy for persistent Pseudomonas aeruginosa infection.

PMID- 12797485
TI  - Procalcitonin as a diagnostic tool in lower respiratory tract infections and
      tuberculosis.
AB  - The diagnostic significance of procalcitonin concentrations in lower respiratory
      tract infections and tuberculosis is not known. A prospective analysis was,
      therefore, performed in patients with acute exacerbation of chronic bronchitis
      (AECB), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and
      tuberculosis and their procalcitonin levels compared with those of patients with
      noninfectious lung diseases (controls). In addition, standard inflammatory
      parameter data were collected. A prospective clinical study was performed with
      four different groups of patients and a control group that consisted of patients
      with noninfectious lung diseases. A total of 129 patients were included: 25 with
      HAP, 26 CAP, 26 AECB, 27 tuberculosis, and 25 controls. C-reactive protein level,
      blood cell counts and procalcitonin concentration were evaluated on the first day
      after onset of clinical and inflammatory symptoms prior to treatment. The median
      procalcitonin concentrations in HAP, CAP, AECB and tuberculosis were not elevated
      in relation to the cut-off level of 0.5 ng x mL(-1). In the HAP group, in four of
      five patients who subsequently died, procalcitonin concentrations of >0.5 ng x
      mL(-1) were found. In acute lower respiratory infections, such as HAP, CAP and
      AECB, significantly elevated levels were found in comparison to the control
      group, but below the usual cut-off level. No differences were observed between
      tuberculosis and the control group. Relative to the current cut-off level of 0.5
      ng x mL(-1), procalcitonin concentration is not a useful parameter for diagnosis
      of lower respiratory tract infections. However, compared to the control group,
      there were significantly elevated levels in patients with hospital-acquired
      pneumonia, community-acquired pneumonia and acute exacerbation of chronic
      bronchitis below the current cut-off level, which should be further investigated.

PMID- 12797486
TI  - Evaluation of a quantitative real-time PCR for the detection of respiratory
      syncytial virus in pulmonary diseases.
AB  - Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract
      infections (ARI) in young children and is involved in exacerbation of chronic
      obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD
      and the viral load in different respiratory diseases has not been investigated to
      date. The present authors established and evaluated a quantitative TaqMan real
      time polymerase chain reaction assay specific for RSV subgroup A. Absolute
      quantification for the determination of viral load input was achieved using a
      control plasmid. The assay allowed for a quantification over a >6-log range and a
      detection limit of <10 RSV copies per reaction mixture. The assay was 30 times
      more sensitive than conventional nested polymerase chain reaction assays.
      Interassay SD was 1.3 and coefficient of variation 4.7% on average. Clinical
      specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were
      compared for viral loads. A total of 47% RSV-positive samples were found in the
      ARI study group and 28% in the COPD study group. The viral load of both study
      groups was found to differ significantly. In the ARI study group the viral load
      was increased almost 2000-fold, suggesting acute infection in this group and
      former or latent infection in the COPD group. Respiratory syncytial virus-A
      specific TaqMan real-time polymerase chain reaction assay is a sensitive and
      rapid method for the determination of viral load in clinical samples. It enables
      differential statements concerning the involvement of respiratory syncytial virus
      in acute lower respiratory tract infections and chronic obstructive pulmonary
      disease to be achieved.

PMID- 12797487
TI  - Prognostic features of residual pleural thickening in parapneumonic pleural
      effusions.
AB  - The objective of the study was the identification of predictive factors for the
      development of residual pleural thickening (RPT) in patients with parapneumonic
      effusion. The design of the prospective study involved investigating patients
      with parapneumonic pleural effusions diagnosed between March 1991 and December
      2000 in the respiratory department of Hospital Ramon y Cajal (Madrid, Spain)
      which is a 1,500 tertiary-care hospital. The clinical and radiological
      characteristics and measurements of microbiological and biochemical variables in
      the pleural fluid taken from the patients were studied. RPT was defined in a
      posteroanterior chest radiograph as pleural thickening of > or = 10 mm measured
      at the lateral chest wall at the level of an imaginary line, tangent to the
      diaphragmatic dome. A total of 48 of the 348 patients studied (13.79%) were found
      to have RPT. Among the factors studied, only presence of pus in the pleural
      space, Fine classes IV and V, temperature > or = 38 degrees C and delayed
      resolution of pleural effusions after diagnosis (> 15 days) were independently
      associated with the risk of RPT. This study showed that significant residual
      pleural thickening was not a common complication of parapneumonic pleural
      effusions. There are certain risk factors for the development of residual pleural
      thickening. However, this complication was not associated with long-term
      functional repercussions in the series of patients involved in this study.

PMID- 12797488
TI  - Urban traffic and pollutant exposure related to respiratory outcomes and atopy in
      a large sample of children.
AB  - Conflicting results have been reported for the relationship between traffic
      exposure and inception of atopy. The effect of traffic on the prevalence of
      asthma and atopy at school age was investigated in a representative population.
      Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied
      using the International Study of Asthma and Allergies in Childhood phase-II
      protocol with skin-prick tests, measurements of specific immunoglobulin E and
      lung function. Traffic exposure was assessed via traffic counts and by an
      emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic
      counts were associated with current asthma, wheeze and cough. In children with
      tobacco-smoke exposure, traffic volume was additionally associated with a
      positive skin-prick test. Cough was associated with soot, benzene and NO2,
      current asthma with soot and benzene, and current wheeze with benzene and NO2. No
      pollutant was associated with allergic sensitisation. High vehicle traffic was
      associated with asthma, cough and wheeze, and in children additionally exposed to
      environmental tobacco smoke, with allergic sensitisation. However, effects of
      socioeconomic factors associated with living close to busy roads cannot be ruled
      out.

PMID- 12797489
TI  - Climate, traffic-related air pollutants and allergic rhinitis prevalence in
      middle-school children in Taiwan.
AB  - The prevalence of allergic rhinitis, a common respiratory disorder, may be
      rapidly increasing. Epidemiological studies, however, indicate little about its
      association with climatic factors and air pollution. The relationship between
      traffic-related air pollutants and allergic rhinitis in middle-school students
      was therefore investigated. In a nationwide survey of middle-school students in
      Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed
      allergic rhinitis and typical symptoms of allergic rhinitis were compared with
      air-monitoring station data on temperature, relative humidity, sulphur dioxide
      (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO) and particulate
      matter with a 50% cut-off aerodynamic diameter of 10 microm (PM10). A total of
      331,686 nonsmoking children attended schools located within 2 km of 55 stations.
      Mean (range) annual exposures were: CO 853 (381-1,610) parts per billion (ppb),
      NOx 35.1 (10.2-72.4) ppb, SO2 7.57 (0.88-21.2) ppb, PM10 69.2 (40.1-116.2) microg
      x m(-3), O3 21.3 (12.4-34.1) ppb, temperature 22.9 (19.6-25.1) degrees C, and
      relative humidity 76.2 (64.8-86.2)%. The prevalence of physician-diagnosed
      allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with
      prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After
      adjustment for age, parental education and history of atopic eczema, physician
      diagnosed allergic rhinitis was found to be associated with higher nonsummer
      (September-May) warmth and traffic-related air pollutants, including CO, NOx and
      O3. Questionnaire-determined allergic rhinitis correlated only with traffic
      related air pollutants. Nonsummer warmth and traffic-related air pollution,
      probably mediated through exposure to common allergens such as dust mites, are
      possible risk factors for allergic rhinitis in middle-school-aged children.

PMID- 12797490
TI  - Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the
      lung of severe COPD patients.
AB  - Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). The current study examined the expression
      of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric
      oxide synthase (iNOS) respectively, in patients with severe COPD and control
      smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS
      and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was
      quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in
      severe COPD compared to control smokers, whereas no difference was observed in
      iNOS+ macrophages. In contrast, severe patients had significantly higher numbers
      of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2
      pneumocytes and their number was inversely related to HO-1+ macrophages. There
      were no significant differences in N-Tyr immunostaining between the two groups.
      However, the rate of protein nitration in lung tissue was directly related to
      iNOS expression and associated with lower values of forced expiratory volume in
      one second/forced vital capacity. HO-2 was constitutively expressed by type 2
      pneumocytes and these cells were increased in severe COPD. In conclusion, the
      results suggest that the enzymes involved in the oxidative stress response may
      have a different role in the lung defence and that imbalance between haem
      oxygenase-1 and inducible nitric oxide synthase may be associated with the
      development of severe impairment in chronic obstructive pulmonary disease
      patients.

PMID- 12797491
TI  - Sleep hypoventilation in hypercapnic chronic obstructive pulmonary disease:
      prevalence and associated factors.
AB  - Sleep hypoventilation (SH) may be important in the development of hypercapnic
      respiratory failure in chronic obstructive pulmonary disease (COPD). The
      prevalence of SH, associated factors, and overnight changes in waking arterial
      blood gases (ABG), were assessed in 54 stable hypercapnic COPD patients without
      concomitant sleep apnoea or morbid obesity. Lung function assessment,
      anthropomorphic measurements, and polysomnography with ABG measurement before and
      after sleep were conducted in all patients. Transcutaneous carbon dioxide tension
      (Pt,CO2) was measured in sleep, using simultaneous arterial carbon dioxide
      tension (Pa,CO2) for in vivo calibration and to correct for drift in the sensor.
      Of the patients, 43% spent > or = 20% of sleep time with Pt,CO2 > 1.33 kPa (10
      mmHg) above waking baseline. Severity of SH was best predicted by a combination
      of baseline Pa,CO2, body mass index and per cent rapid-eye movement (REM) sleep.
      REM-related hypoventilation correlated significantly with severity of inspiratory
      flow limitation in REM, and with apnoea/hypopnoea index. Pa,CO2 increased mean+/
      SD 0.70+/-0.65 kPa (5.29+/-4.92 mmHg) from night to morning, and this change was
      highly significant. The change in Pa,CO2 was strongly correlated with severity of
      SH. Sleep hypoventilation is common in hypercapnic chronic obstructive pulmonary
      disease, and related to baseline arterial carbon dioxide tension, body mass index
      and indices of upper airway obstruction. Sleep hypoventilation is associated with
      significant increases in arterial carbon dioxide tension night-to-morning, and
      may contribute to long-term elevations in arterial carbon dioxide tension.

PMID- 12797492
TI  - Glucocorticoid receptor-binding characteristics in severe asthma.
AB  - The cellular mechanisms associated with severe asthma are still poorly
      understood. This study investigated the association between glucocorticoid
      receptor (GR) alterations and continuous oral glucocorticoid therapy requirement
      in severe asthma. GR-binding affinity (Kd) and receptor number (n) in peripheral
      blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated,
      intermittent asthmatics and 10 severe asthmatics were assessed. Moreover, one
      ability of dexamethasone to inhibit regulated on activation, T-cells expressed
      and secreted (RANTES) release by these cells in vitro was investigated. GR
      binding characteristics were studied in PBM using a 3H dexamethasone ligand
      binding assay and Scatchard analysis. RANTES release was measured in the
      supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay. No
      significant differences in Kd and n were found between the three groups of
      patients. Dexamethasone in vitro was able to inhibit RANTES release (mean+/-SEM),
      with the same concentration/response curve in intermittent, untreated asthmatics
      (0.47+/-0.22 versus 1.64+/-0.31 ng x mL(-1)) and severe asthmatics (1.49+/-0.64
      versus 2.59+/-0.77 ng x mL(-1)). This study showed that, despite long-term
      treatment with oral glucocorticoids, there was no evidence of abnormalities in
      glucocorticoid receptor-binding characteristics in severe asthma, and moreover,
      it was demonstrated that glucocorticoid receptors were functional in vitro.

PMID- 12797493
TI  - Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids.
AB  - The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared
      by the McKenzie skin-blanching test and taken as an index of relative potency.
      The rationale for the present study was to transpose the McKenzie test to the
      airway and to compare the airway vascular effects of three inhaled GS:
      beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide
      (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert
      gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD
      Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1)
      in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics
      (n=10). All GS caused a transient decrease in Qaw. The magnitude of the
      vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect
      of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3
      and 3.0, respectively, in healthy subjects, as assessed by the dose required to
      decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore,
      measuring airway blood flow may be a useful, site-specific parameter to assess
      the tissue bioavailability and vasoconstrictive efficacy of inhaled
      glucocorticosteroids.

PMID- 12797494
TI  - Possible anti-inflammatory effect of salmeterol against interleukin-8 and
      neutrophil activation in asthma in vivo.
AB  - In-vitro data suggest that long-acting beta2-agonists may have a neutrophil
      stabilising effect. A reduction in airway wall eosinophil number following
      introduction of salmeterol in persistent asthma has previously been described.
      There is currently interest in the "neutrophil system" in asthma, and thus the
      aim of the present study was to investigate the effect of salmeterol on
      interleukin (IL)-8, neutrophils and myeloperoxidase (MPO) in persistent asthma.
      In the same 12-week double-blind parallel-group placebo-controlled study as
      described previously, the effects on bronchoalveolar lavage fluid (BALF) IL-8,
      neutrophils and MPO of introducing salmeterol (50 microg b.i.d.) or giving
      additional inhaled corticosteroid (fluticasone 100 microg b.i.d.) in 45 subjects
      with persistent asthma already on low/moderate doses of inhaled corticosteroids
      were further investigated. At baseline, BALF IL-8 but not neutrophil or MPO
      levels were significantly raised in the asthmatic subjects compared to normal
      controls. MPO levels correlated strongly with IL-8 levels, and weakly with BALF
      neutrophil numbers in the asthmatics. Fluticasone treatment resulted in
      significantly elevated neutrophil numbers, but not MPO or IL-8 levels. In
      contrast, introducing salmeterol significantly reduced IL-8 and MPO levels, but
      did not affect BALF neutrophil numbers. Interestingly, salmeterol and fluticasone
      showed significantly contrasting effects on MPO and neutrophils, and there was a
      divergent effect on IL-8 levels that almost reached significance. Excessive
      interleukin-8 levels may be relevant to asthma pathogenesis, even in the setting
      of moderate-dose inhaled corticosteroid therapy. Reduction in interleukin-8
      production and possibly stabilisation of airway neutrophil numbers may explain
      the greater clinical benefit of adding a long-acting beta2-agonist rather than
      merely increasing inhaled corticosteroid doses. Indeed, high-dose inhaled
      corticosteroid therapy alone may promote airway neutrophilia.

PMID- 12797495
TI  - The economic impact of preschool asthma and wheeze.
AB  - The aim of the present study was to determine the economic impact in the UK of
      wheezing disorders in preschool children. Health, societal and family-borne costs
      were calculated for a sample of 94 preschool children who attended hospital with
      a primary diagnosis of wheeze or asthma during 1998/1999. Sample costs were
      calculated using data from a structured interview schedule and from symptom
      diaries completed by trial parents, patients' general practice and hospital
      records, and hospital finance data. Health costs for 1-5-yr-olds in the UK were
      calculated using data from a postal population survey in the same region. It is
      estimated that 1-5-yr-old children with wheeze in the UK cost the health service
      a total of 53 million UK pounds (GBP). The greatest expenditure, 34 million GBP,
      was for primary care, representing 65.2% of total healthcare costs. Prescription
      costs represented 20.4% (11 million GBP) of total healthcare costs. Caring for
      preschool children with wheeze in the UK cost the health service 0.15% of its
      total budget in 1998/1999. The total costs to society of caring for the 0.88% of
      preschool children who attended hospital for asthma or wheeze in a year
      represented a further 2.6 million UK pounds. Primary prevention strategies at the
      population level promise more cost savings than any attempt at decreasing
      hospitalisations in those more severely ill.

PMID- 12797496
TI  - Distribution of technetium-99m-labelled QVAR delivered using an Autohaler device
      in children.
AB  - QVAR, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has
      been shown to double lung deposition in adults. The aim of the present study was
      to assess the total body deposition and distribution of technetium-99m-labelled
      (99mTc) QVAR in children after inhalation via an Autohaler. Sixteen male
      asthmatic children (5-14 yrs) inhaled labelled drug (<4 MBq 99mTc; 100 microg
      beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200
      microg) administration. Simultaneous anterior and posterior planar scintigraphic
      scans (120 s acquisition time) were collected after inhalation of labelled drug.
      Mean+/-SD lung deposition of labelled drug (attenuation-corrected; percentage of
      ex-actuator dose) was 36.9+/-9.2, 46.5+/-11.6 and 54.1+/-10.7% in children aged 5
      7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal
      deposition was 59.7+/-8.2, 48.9+/-12.3 and 40.3+/-11.8%. Lung deposition
      positively correlated with the forced expiratory volume in one second (FEV1) and
      forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the
      FEV1, FVC, height and age. In older children (11-14 yrs), lung deposition was
      almost identical to that reported in adults using QVAR. In children aged 5-10
      yrs, lung deposition using QVAR was greater than the levels measured using other
      commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition
      was inversely related to age.

PMID- 12797497
TI  - Reduced lung function and risk of atrial fibrillation in the Copenhagen City
      Heart Study.
AB  - Chronic obstructive pulmonary disease has been associated with a high frequency
      of arrhythmias. Few studies have analysed the role of reduced lung function in
      predicting atrial fibrillation (AF). The aim of the present study was to
      investigate the relationship between forced expiratory volume in one second
      (FEV1) and risk of first episode of AF in a prospective study. Data from 13,430
      males and females without previous myocardial infarction, who participated in the
      Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination
      after 5 yrs and by hospital admission for AF during a period of 13 yrs.
      Multivariate analyses were used with adjustment for cardiopulmonary risk factors.
      There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%)
      diagnosed at hospitalisations. Risk of new AF at re-examination was 1.8-times
      higher for FEV1 between 60-80% of predicted compared with FEV1 > or = 80% after
      adjustment for sex, age, smoking, blood pressure, diabetes and body mass index.
      The risk of AF hospitalisation was 1.3-times higher for FEV1 between 60-80% and
      1.8-times higher for FEV1 < 60% compared with FEV1 > or = 80%, when additional
      adjustment was made for education, treatment with diuretics and chest pain at
      activity. The authors conclude that reduced lung function is an independent
      predictor for incident atrial fibrillation.

PMID- 12797498
TI  - Sex differences in lung vulnerability to tobacco smoking.
AB  - Studies have indicated that females are more vulnerable to the deleterious effect
      of tobacco smoking than males. The current study aimed to investigate the
      associations between tobacco smoking and reported respiratory symptoms, self
      rated health, and lung function by sex. In 1995-1997 65,225 subjects aged > or =
      20 yrs (71% of invited) attended for screening within the Nord-Trondelag Health
      Study. Among these, 10,941 subjects selected randomly or because they reported
      having asthma or asthma-related symptoms, participated in the Bronchial
      Obstruction in Nord-Trondelag study consisting of spirometry and a personal
      interview. Tobacco smoking was associated with increased prevalence of
      respiratory symptoms, reduced lung function, and lower score on global self-rated
      health (SRH). Adjusted for smoking burden and lung function, females had a higher
      risk for reporting respiratory symptoms and lower SRH compared with males.
      Further, smoking burden was associated with a larger relative reduction in
      expiratory lung function in females than in males. Females reported more symptoms
      and lower self-rated health compared with males with similar smoking burden. Even
      if smoking in females was associated with a larger reduction in per cent
      predicted lung function compared with males, this does not fully explain the
      higher symptom prevalence in females.

PMID- 12797499
TI  - The early allergic response in small airways of human precision-cut lung slices.
AB  - To study the role of small airways in the early allergic response (EAR), the
      method of human precision-cut lung slices (PCLS) was developed and used to
      examine the bronchoconstriction elicited by passive sensitisation and allergen
      provocation. Viable human PCLS of 250-microm thickness containing airways <1.5 mm
      in outer diameter were prepared from lung lobes obtained from lung resection and
      taken into culture. According to the low release of lactate dehydrogenase and the
      constant ciliary beat frequency, human PCLS were viable for at least 3 days.
      Following overnight passive sensitisation with serum from allergic individuals,
      administration of grass-pollen extract or activating immunoglobulin E antibody
      resulted in immediate airway contraction that was quantified by videomicroscopy.
      The extent of the EAR increased with decreasing airway size (outer airway
      diameter), with the strongest response occurring in the terminal bronchioles.
      Histamine receptor antagonism was ineffective, and leukotriene or thromboxane
      receptor antagonism attenuated the early allergic response only in some cases.
      However, simultaneous blockade of leukotriene and thromboxane receptors almost
      completely prevented the early allergic response in the precision-cut lung slices
      from all individuals, suggesting such a dual treatment as a potential future
      asthma therapy.

PMID- 12797500
TI  - Peripheral airway involvement in asthma assessed by single-breath SF6 and He
      washout.
AB  - The aim of the study was to assess how deep into the acinar region the airway
      response to cold dry-air hyperventilation challenge (CACh) reaches in subjects
      with asthma of different severity. Peripheral airway function was measured using
      a single-breath sulphur hexafluoride (SF6) and helium (He) washout test and
      overall airway function by forced expiratory volume in one second (FEV1) at rest,
      after CACh and beta2-therapy in 55 adults with a history of asthma. The
      normalised phase-III slopes (SnIII) for SF6 and He were used to assess peripheral
      airway obstruction and the (SF6-He) SnIII difference to indicate where
      obstruction occurred. While a greater He versus SF6 slope increase indicates a
      response close to the acinar entrance, the reverse indicates a response deeper
      into the acinar airspaces. Twelve subjects had a major fall in FEV1 (> or = 20%)
      after CACh, 16 a minor fall (10-19%), and 27 did not react. Resting He and SF6
      SnIII were significantly greater in major responders with respect to minor and
      nonresponders, while resting FEV1 did not differ between the three groups. The
      major responders showed marked increases of He and SF6 SnIII after CACh, with
      greater increase for He resulting in a negative (SF6-He) SnIII difference. To
      conclude, airways close to the acinar entrance participate in the overall airway
      response to cold-air challenge in asthmatic adults with marked airway
      hyperresponsiveness to cold, dry air.

PMID- 12797501
TI  - Induction of type-IIA secretory phospholipase A2 in animal models of acute lung
      injury.
AB  - The aim of this study was to evaluate the presence of type-II secretory
      phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the
      destruction of surfactant in three rat models of acute lung injury. Alveolar
      instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted
      in a significant increase in lung oedema and in a decrease in static compliance
      of the respiratory system together with alveolar-neutrophil influx as compared
      with healthy control rats. The upregulation of messenger ribonucleic acid and
      sPLA2-IIA by the lung was evident. This was associated with surfactant
      degradation and a decrease in large:small ratio of surfactant aggregates in
      bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA
      activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha
      naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase
      in sPLA2-IIA activity was observed. Additional experiments in rats treated with a
      specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1
      benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no
      improvement in physiological parameters despite a biochemical effect, suggesting
      that its activity is only one of the multiple factors involved in the
      pathophysiology of lung injury.

PMID- 12797502
TI  - Inhaled synthetic surfactant abolishes the early allergen-induced response in
      asthma.
AB  - Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway
      oedema and consequently potentiate the severity of the asthmatic response. A
      randomised, single-blind, cross-over study of an inhaled synthetic phospholipid
      dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects
      with previously documented early and late asthmatic responses (EAR and LAR) to an
      inhaled allergen. This was conducted to evaluate the role of exogenous surfactant
      administration on EAR and LAR. A total of seven subjects had complete evaluable
      data and received the full dose of Pumactant. Asthmatic subjects inhaled two
      separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose
      was administered 8 h in advance and the second dose 30 min in advance. The dosage
      occurred through a purpose-built administration device. This was followed by a
      standard bronchial-provocation test, and forced expiratory volume in one second
      (FEV1) was measured at regular intervals over a 10-h period. Pumactant was well
      tolerated and, surprisingly, abolished the EAR but not the LAR in all seven
      subjects. The mean area under the curve between 0-2 h (EAR) following bronchial
      provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for
      the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and
      23.98% in the PT and the NT group, respectively. The demonstration of inhibition
      of the early asthmatic response by exogenous surfactant, provides the first
      evidence that pulmonary surfactant dysfunction may also contribute to the very
      early asthmatic response to allergen. Exogenous surfactant administration could
      serve as a useful adjunct in controlling the early allergen-induced symptoms in
      patients with allergic asthma.

PMID- 12797503
TI  - Indirect airway challenges.
AB  - Indirect challenges act by causing the release of endogenous mediators that cause
      the airway smooth muscle to contract. This is in contrast to the direct
      challenges where agonists such as methacholine or histamine cause airflow
      limitation predominantly via a direct effect on airway smooth muscle. Direct
      airway challenges have been used widely and are well standardised. They are
      highly sensitive, but not specific to asthma and can be used to exclude current
      asthma in a clinic population. Indirect bronchial stimuli, in particular
      exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may
      reflect more directly the ongoing airway inflammation and are therefore more
      specific to identify active asthma. They are increasingly used to evaluate the
      prevalence of bronchial hyperresponsiveness and to assess specific problems in
      patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation
      before scuba diving. Direct bronchial responsiveness is only slowly and to a
      modest extent, influenced by repeated administration of inhaled steroids.
      Indirect challenges may reflect more closely acute changes in airway inflammation
      and a change in responsiveness to an indirect stimulus may be a clinically
      relevant marker to assess the clinical course of asthma. Moreover, some of the
      indirect challenges, e.g. hypertonic saline and mannitol, can be combined with
      the assessment of inflammatory cells by induction of sputum.

PMID- 12797504
TI  - Pulmonary echinococcosis.
AB  - Echinococcosis or hydatid disease is caused by larvae of the tapeworm
      Echinococcus. Four species are recognised and the vast majority of infestations
      in humans are caused by E. granulosus. E. granulosus causes cystic
      echinococcosis, which has a worldwide distribution. Humans are exposed less
      frequently to E. multilocularis, which causes alveolar echinococcosis. E. vogeli
      and E. oligarthrus are rare species and cause polycystic echinococcosis. In
      cystic echinococcosis, humans are an accidental host and are usually infected by
      handling an infected dog. The liver and lungs are the most frequently involved
      organs. Pulmonary disease appears to be more common in younger individuals.
      Although most patients are asymptomatic, some may occasionally expectorate the
      contents of the cyst or develop symptoms related to compression of the
      surrounding structures. Other symptoms of hydatid disease can result from the
      release of antigenic material and secondary immunological reactions that develop
      from cyst rupture. The cysts are characteristically seen as solitary or multiple
      circumscribed or oval masses on imaging. Detection of antibody directed against
      specific echinococcal antigens is found in only approximately half of patients
      with pulmonary cysts. Surgical excision of the cyst is the treatment of choice
      whenever feasible.

PMID- 12797505
TI  - Lung infiltrate in a male with a bronchopleural fistula.

PMID- 12797506
TI  - Levalbuterol toxicity: no reason to be jittery.

PMID- 12797507
TI  - Performing cardiac MR imaging: an overview.
AB  - Because of the enormous economic and social impact of cardiovascular disease in
      the United States, there is a need for improved noninvasive diagnosis. Cardiac MR
      imaging is a versatile, comprehensive technique for assessing cardiac morphology
      and function. With an understanding of cardiac anatomy and physiology as well as
      MR physical principles, cardiac MR imaging can be performed and play an important
      role in patient management.

PMID- 12797508
TI  - Setting up a clinical cardiac MR imaging program: practical issues and economics.
AB  - Use of MR imaging to assess the heart has grown rapidly in recent years. MR
      imaging can assess cardiac anatomy, quantify ventricular and valvular function,
      identify regions of infarcted myocardium, and evaluate flow-limiting coronary
      artery stenoses better than any other single imaging modality. Despite its
      superior capabilities, cardiac MR imaging has yet to be adopted widely in
      clinical practice, in part because of the many obstacles to developing a clinical
      cardiac MR imaging program. The purpose of this article is to provide information
      that may be helpful in developing such a program. The information is based on the
      authors' experience in an inpatient hospital setting and an outpatient private
      practice. The recommendations reflect personal opinions and donot represent
      requirements of any organization or society unless otherwise indicated.

PMID- 12797509
TI  - MR imaging of congenital heart disease.
AB  - MR examination of patients with congenital heart disease is a useful means of
      explicitly demonstrating chamber morphology and, in particular, morphologic
      changes caused by physiologic changes brought on by particular defects. Use of MR
      techniques allows characterization of chamber morphology for determination of
      cardiac connections and great artery relationships. The high-contrast resolution
      of spin echo acquisition provides important morphologic detail. Cine gradient
      echo techniques complement spin echo acquisition by providing functional and flow
      information. Although MR examination complements echocardiographic investigation
      in pediatric and adult patients, is may be useful for replacing
      angiocardiography, shortening examination time, and decreasing morbidity in
      diagnostic workups of these patients.

PMID- 12797510
TI  - MR imaging of myocardial perfusion and viability.
AB  - CMR is a rapidly developing new modality with applications in clinical cardiology
      for detection and assessment of myocardial ischemia and viability. CMR perfusion
      results for the detection of ischemia in comparison with stress echocardiography
      and scintigraphic techniques are reasonable, but all the studies reported to date
      have been conduced in selected patients. Larger studies in patient populations
      reflecting a broader spectrum of disease are necessary before perfusion CMR can
      be envisaged as a clinically reliable and robust diagnostic tool. Other CMR
      techniques provide a variety of novel methods of obtaining information on
      postischemic viability. Signs of viability that can be observed by CMR are the
      absence of late gadolinium-based contrast enhancement in a myocardial region
      involved in a recent infarct, any sign of wall thickening at rest (which is
      detectable with high accuracy by CMR), wall thickening after stimulation by low
      dose dobutamine, and preserved wall thickness. Conversely, myocardial necrosis is
      characterized by signal enhancement of the infarct area after injection of Gd
      DTPA, reduced wall thickness in chronic infarcts, and absence of a contractile
      reserve during dobutamine stimulation. Dobutamine CMR and late enhancement
      contrast-enhanced CMR predict contractile improvement after revascularization.

PMID- 12797511
TI  - Assessment of cardiac function with MR imaging.
AB  - A variety of black or white blood imaging techniques are available for assessing
      global and regional LV and RV function during cardiovascular MR imaging
      examinations. In addition to providing information about LV function at rest,
      these techniques provide diagnostic and prognostic information regarding
      myocardial ischemia and viability during MR imaging stress tests.

PMID- 12797512
TI  - Coronary MR angiography clinical applications and potential for imaging coronary
      artery disease.
AB  - Over the past decade, CMRA has emerged as a unique clinical imaging tool with
      applications in selected populations. Patients with suspected coronary artery
      anomalies and patients with Kawasaki disease and coronary aneurysms are among
      those for whom CMRA has demonstrated clinical usefulness. For assessment of
      patients with atherosclerotic CAD, CMRA is useful for detection of patency of
      bypass grafts. At centers with appropriate expertise and resources, CMRA also
      appears to be of value for exclusion of severe proximal multivessel CAD in
      selected patients. Data from multicenter trials will continue to define the
      clinical role of CMRA, particularly as it relates to assessment of CAD. Future
      developments and enhancements of CMRA promise better lumen and coronary artery
      wall imaging. This may become the new target in noninvasive evaluation of CAD.

PMID- 12797513
TI  - MR imaging for the noninvasive assessment of atherothrombotic plaques.
AB  - Imaging methods to quantify the progression and regression of atherosclerosis
      could play a strong role in the management of patients. High-resolution,
      noninvasive MR imaging may provide exhaustive 3D anatomical information about the
      lumen and the vessel wall. Furthermore, MR imaging has the ability to
      characterize plaque composition and microanatomy and therefore to identify
      lesions vulnerable to rupture or erosion. The high resolution of MR imaging and
      the development of sophisticated contrast agents offer the promise of molecular
      in vivo molecular imaging of the plaque. This may aid early intervention (eg,
      lipid-lowering drug regiments) in both primary and secondary treatment of
      vascular disease in all arterial beds.

PMID- 12797514
TI  - Assessment of valve disease: qualitative and quantitative.
AB  - Evaluation of valve disease has changed significantly with the development of
      color Doppler echocardiography. Nevertheless, this technique has limitations,
      particularly in the assessment of valvular regurgitation. MR imaging, with its
      ability to provide three-dimensional morphologic data, dynamic cine information,
      and functional evaluation with flow-sensitive techniques, can be envisioned as a
      complementary noninvasive modality, able to provide the complete information
      required for planning therapeutic options. With MR imaging, qualitative as well
      as accurate and reproducible quantitative information such as volume
      measurements, cardiac function, and flow velocity profiles are unique for the
      evaluation of the severity of valve disease. This article reviews the different
      MR imaging techniques used in assessing valvular heart disease and discusses the
      advantages and limitations of these techniques in current clinical applications
      in comparison with classical imaging methods.

PMID- 12797515
TI  - MR imaging of the thoracic aorta.
AB  - There are numerous pulse sequences available for evaluating the diverse pathology
      that affects the thoracic aorta. Preliminary imaging using TrueFISP and
      precontrast and postcontrast T1 GRE-FS is usually required to assess morphology
      of the aorta and adjacent structures. CE-MRA is the mainstay in the investigative
      approach. The addition of temporally resolved subsecond CE-MRA is particularly
      useful for assessing high-flow vascular lesions such as shunts, while at the same
      time not adding much to the overall contrast load. PC-MRA may help further
      characterize stenotic lesions and can be useful for monitoring progression of
      disease.

PMID- 12797516
TI  - Imaging of pericardial disease.
AB  - Pericardial pathology is most often identified by its effect on cardiac function.
      Echocardiography is usually performed first in evaluation of pericardial disease,
      but is occasionally limited or indeterminate. MR imaging is often helpful in
      these cases, offering superior soft tissue contrast and the ability to image the
      entire pericardium and its relationship to cardiac structure and function. Many
      of the techniques recently developed for myocardial imaging are equally
      applicable to the pericardium and frequently assist in the diagnosis of
      pericardial disease. In this article, the authors review MR imaging techniques
      for pericardial imaging, discuss the appearance of the normal pericardium, and
      illustrate pathologic and congenital conditions of the pericardium.

PMID- 12797517
TI  - MR imaging of arrhythmogenic right ventricular dysplasia.
AB  - MR imaging is helpful in the management of patients in whom the diagnosis of ARVD
      or RVOTT is suspected. Careful attention to cardiac rate control will minimize or
      eliminate ventricular extrasystolic beats during examination, which will improve
      image quality and confidence in diagnosis. Use of thin-section cine gradient echo
      acquisition provides a means of identifying regional wall motion abnormalities,
      characteristic of the regional dysfunction in these diseases. Furthermore,
      application of spin echo or double inversion recovery imaging may provide
      visualization of abnormally thin or fat-infiltrated regions of right ventricular
      free wall myocardium, providing additional diagnostic criteria for the diagnosis
      of these diseases.

PMID- 12797518
TI  - MR evaluation of cardiac and pericardial malignancy.
AB  - The accurate evaluation of cardiac masses by MR imaging was established in the
      infancy of cardiac MR imaging. From its advent, MR imaging was believed to be
      diagnostically superior to echocardiography in the evaluation of suspected
      cardiac masses. Though excellent in its assessment of the left side of the heart,
      echocardiography is limited in its evaluation of the right heart, mediastinum,
      and paracardiac structures. It is also of limited use in patients with emphysema
      and chest wall deformities. With the advent of ECG gating, MR imaging's ability
      to assess the presence and anatomy of cardiac and paracardiac masses was well
      established by a number of studies. This research also demonstrated MR imaging's
      capacity to exclude a cardiac mass when the echocardiogram was equivocal.

PMID- 12797519
TI  - Estrogen and progesterone modulate monocyte cell cycle progression and apoptosis.
AB  - PROBLEM: Pregnancy is characterized by dramatic immunologic changes most commonly
      characterized as suppression of cell-mediated immunity. Mechanisms of this
      immunosuppression are obscure but may be caused by increases in pregnancy
      associated sex steroids such as 17-beta-estradiol or progesterone. METHOD OF
      STUDY: Using five myelomonocytic cell lines in various stages of differentiation,
      the effects of 17-beta-estradiol and progesterone on cell cycling, apoptosis, and
      bcl-2 expression in randomly cycling cells before and after lipopolysaccharide
      (LPS) activation were examined. RESULTS: Lipopolysaccharide alone inhibited cell
      cycle progression in THP-1 monocyte-like cells and U-937 histiocyte-like cells.
      Estrogen alone produced cell cycle arrest in all myelomonocytic cells except HL
      60 pro-myelocyte-like cells. Progesterone had effects predominantly on pro
      myelocytic-like HL-60 cells, inducing apoptosis. Estrogen and progesterone both
      decreased levels of bcl-2 in KG-1alpha, HL-60, and THP-1 cells. LPS partially
      antagonized both estrogen-induced THP-1 apoptosis and its suppression of bcl-2
      protein. CONCLUSIONS: Sex steroid-induced effects on cell cycle transition and
      apoptosis are potential mechanisms by which pregnancy-induced cell-mediated
      immune suppression may occur. Further investigation should provide a better
      understanding of pregnancy-induced immune changes and, perhaps, sex-based
      differences in monocyte function and immunologic responses.

PMID- 12797520
TI  - Expression of nuclear factor of activated T cells mRNA in maternal peripheral
      blood cells.
AB  - PROBLEM: In T lymphocytes, nuclear factor of activated T cells (NF-AT) regulates
      the induction of cytokine genes upon antigenic stimulation. This study was
      designed to analyse the relationship between NF-AT and pregnancy. METHOD OF
      STUDY: With informed consent, peripheral blood cells (PBCs) were obtained from
      non-pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The
      expression of NF-AT2 and NF-AT3 mRNAs in PBCs was measured by a quantitative
      reverse transcriptase-polymerase chain reaction method. RESULTS: In the early
      pregnancy period, in successful pregnancy, both NF-AT2 and NF-AT3 mRNAs increased
      significantly, whereas in cases of spontaneous abortion they did not change
      significantly. After peaking, they decreased gradually and were re-elevated in
      the ninth and tenth gestational month. In the puerperal period, NF-AT3 mRNAs
      decreased, but NF-AT2 mRNA showed a comparatively high expression level.
      CONCLUSION: These findings suggested that in humans NF-AT signal transduction
      might be involved in alloantigenic recognition and tolerance and play important
      roles, especially in the early and late period of pregnancy.

PMID- 12797521
TI  - Intracellular expression of CD69 in endometrial and peripheral T cells represents
      a useful marker in women with recurrent miscarriage: modulation after allogeneic
      leukocyte immunotherapy.
AB  - PROBLEM: To characterize in fertile women and women with recurrent spontaneous
      abortions (RSA) the expression and functional status of T cells expressing the
      CD69 molecule. METHOD OF STUDY: We analyzed by flow cytometry in peripheral blood
      and endometrium from fertile and RSA women, the surface and cytoplasmic
      expression of CD69 on gated T cells. In addition, we investigated by three-color
      flow cytometry the expression of cytokines, and subsets of memory T cells.
      RESULTS: In T cells, CD69 was restricted to the intracellular compartment with a
      higher frequency in RSA than in fertile women (68.2 +/- 12% versus 23.7 +/- 22%,
      P < 0.001, and 20 +/- 9.5% versus 2.1 +/- 3.8%, P < 0.005, in endometrium and
      peripheral blood, respectively). In contrast, the number of interferon-gamma+
      (IFN-gamma+) secreting cells was higher (16 +/- 5% versus 6 +/- 1%) in fertile
      women. All 11 RSA women alloimmunized with parental leukocytes reached values of
      CD3 +/- CD69+ cells similar to those observed in fertile women. CONCLUSIONS: CD69
      might represent a useful marker in the diagnosis and the follow up of RSA
      patients.

PMID- 12797522
TI  - TNF-alpha protects embryos exposed to developmental toxicants.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in
      mediating post-implantation embryo loss or the embryonic maldevelopment induced
      by development toxicants or maternal metabolic imbalances. In order to clarify
      the role of TNF-alpha further, a comparative study was performed in TNF-alpha,
      knockout and TNF-alpha, positive mice, exposed to a reference teratogen,
      cyclophosphamide (CP). METHODS: Cyclophosphamide was injected on day 12 of
      pregnancy and 18-day fetuses were examined for external structural anomalies.
      Apoptosis and cell proliferation were measured by TdT-mediated biotin-dUTP nick
      end labeling and 5'-bromo-2'-deoxyuridine incorporation, respectively, in the
      brain (an organ, sensitive to the teratogen) of embryos 24 hr after CP injection.
      NF-kappaB DNA-binding activity by electrophoretic mobility shift assay (EMSA) and
      the expression of Re1lA (an NF-kappaB subunit) and I(kappa)B(alpha) proteins by
      Western blot analysis were assessed in the brain of embryos tested 24 and 48 hr
      after CP treatment. RESULTS: Surprisingly, the proportion of fetuses with
      craniofacial, trunk and severe limb reduction anomalies were significantly higher
      in TNF-alpha -/- females, than in TNF-alpha,+/+ mice. Excessive apoptosis and
      suppression of cell proliferation was found in the brain, and they were more
      prominent in TNF-alpha -/- than TNF-alpha +/+ embryos, when examined 24 hr after
      CP injection. Finally, CP-induced suppression of NF-kappaB DNA-binding activity
      was found to be enhanced in the brain of TNF-alpha -/- embryos, and the
      restoration of NF-kappaB DNA-binding activity was compromised. CONCLUSION: This
      work demonstrates for the first time that TNF-alpha may act as a protector of
      embryos exposed to teratogenic stress. One possible mechanism may be restoration
      of NF-kappaB activity in embryonic cells surviving the teratogenic insult.

PMID- 12797523
TI  - Chemokine bioactivity of RANTES is elevated in the sera of infertile women with
      past Chlamydia trachomatis infection.
AB  - PROBLEM: It has been shown that Chlamydia trachomatis infection in infertile
      women is highly associated with tubal pathology. Chlamydia trachomatis antibody
      testing is a simple screening test for tubal factor subfertility, however, it is
      based on the detection of previous infection. Recently, association between some
      inflammatory diseases and chemokines has been investigated. This study was
      performed to clarify the relationship between chemokines in the sera of infertile
      women and past C. trachomatis infection. METHOD OF STUDY: Serum samples were
      collected from 10 infertile women having C. trachomatis antibodies
      [immunoglobulin (Ig)G and/or IgA] in their sera and 10 infertile women without
      the antibodies. All patients' tubo-ovarian structures were explored by
      transvaginal hydrolaparoscopy (THL). A CXC chemokine, interleukin-8, and six CC
      chemokines including macrophage inflammatory protein-1alpha (MIP-1alpha), MIP
      1beta, monocyte chemotactic protein-1 (MCP-1), MCP-3, eotaxin, and regulated on
      activation, normal T cell expressed and secreted (RANTES) concentrations in their
      sera were analyzed using enzyme-linked immunosorbent assay. RESULTS: The serum
      concentration of RANTES was significantly higher in patients with C. trachomatis
      antibodies than those without the antibodies (P = 0.019). However, there were no
      significant differences of the concentrations of other chemokines between the
      sera of infertile women with and without C. trachomatis antibodies. The
      concentration of RANTES in the sera of infertile women did not correlate with C.
      trachomatis antibody titers or tubal pathology diagnosed by THL. CONCLUSIONS:
      These findings might indicate significant roles of some chemokines in the
      pathogenesis of C. trachomatis infection. Further studies are necessary to study
      the usefulness of evaluations of chemokines in tubal infertility investigations.

PMID- 12797524
TI  - Necrotic feature of the trophoblasts lacking HLA-G expression in normal and pre
      eclamptic placentas.
AB  - PROBLEM: Human leukocyte antigen (HLA)-G is thought to be expressed in all
      placental extravillous trophoblasts (EXTs). In pre-eclamptic placentas, a lack of
      HLA-G expression on EXTs had been found, and deduced as a possible cause of pre
      eclampsia. However, a subset of EXTs lacking expression of HLA-G can also be
      found in normal placenta. Therefore, we sought to compare these cells in normal
      and pre-eclamptic placentas. METHODS OF STUDY: Frozen sections of normal and pre
      eclamptic placentas were examined by immunohistochemical staining using HLA-G
      monoclonal antibody 87G, histochemical enzymatic analysis of succinate
      dehydrogenase (SDH) and ultrastructural analysis. RESULTS: A subset of EXTs
      lacking HLA-G expression was found in both normal and pre-eclamptic placentas.
      These cells showed necrotic features such as the swelling of cells, eosin
      achromatophilia, the loss of SDH activity and swelling mitochondria. Cells from
      both tissues were identical with regard to these features. CONCLUSION: The
      features of the EXTs lacking HLA-G expression indicated they had undergone
      necrosis and thus could not express HLA-G protein. Therefore, an alternative
      interpretation to the lack of HLA-G expression in pre-eclamptic placentas is that
      it is the result of cell death and not the cause.

PMID- 12797525
TI  - Natural killer (NK) cell receptors' repertoire in couples with recurrent
      spontaneous abortions.
AB  - PROBLEM: Natural killer (NK) cell receptors (NKRs) have been suggested to protect
      trophoblast, but their function at the fetomaternal interface remains unknown. To
      investigate if the outcome of pregnancy depends on women's NKRs, we studied the
      NKR repertoire in couples with recurrent spontaneous abortions (RSA). METHODS:
      Twenty-six childless couples with > or = 2 abortions, characterized by alloimmune
      abnormalities, and 26 control couples were genotyped for five killer
      immunoglobulin-like receptors (KIR) and two CD94/NKG receptors, known to have as
      ligands human leukocyte antigen (HLA) class I molecules with trophoblastic
      expression: inhibitory 2DL1,2,3 and activating 2DS1,4 KIRs, inhibitory NKG2A and
      activating NKG2C. Detected repertoires of women and partners were compared
      between the two groups. RESULTS: Less aborters than controls were found to have
      all three inhibitory KIRs (30.77% versus 69.23%, P = 0.01), some of them had only
      one inhibitory KIR (19.23% versus 3.85%, P = 0.08) and most of them were lacking
      inhibitory KIRs possessed by their husbands (57.69% versus 15.38%, P = 0.001).
      CONCLUSIONS: Women with alloimmune abortions have a limited inhibiting KIR
      repertoire and such miscarriages may occur because trophoblastic HLA class I
      molecules are recognized by decidual NK cells lacking the appropriate inhibitory
      KIRs.

PMID- 12797526
TI  - Cleavage line patterns in beagle dogs: as a guideline for use in dermatoplasty.
AB  - We prepared a map of the cleavage lines for beagle dogs, as a guideline for use
      of cleavage lines in dermatoplasty. The cleavage lines at the head resembled the
      orientation of the underlying muscles. Although the cleavage lines in the trunk
      were perpendicular to the body axis, those in the thoraco-abdominal region were
      parallel to the body axis. The cleavage lines at the limbs were parallel to the
      long axis of the limb on the cranial surface, but were perpendicular to the long
      axis of the limb on the lateral and caudal surfaces. Also, we recorded in detail
      the cleavage lines in the distal regions of the limbs.

PMID- 12797527
TI  - The effect of testosterone on gastrocnemius muscle fibres in growing and adult
      male and female rats: a histochemical, morphometric and ultrastructural study.
AB  - In this study, the effect of testosterone on gastrocnemius muscle fibres in
      growing and adult rats (male and female) was examined using histochemical,
      morphometric and ultrastructural techniques. After physiological saline (PS),
      olive oil (OvO) or olive oil + testosterone (OvOT) injections on 72 rats (growing
      and mature, 36 male and 36 female), the sample tissues of fibre types of the
      gastrocnemius muscle taken were examined by histochemical [alkaline adenosine
      triphosphatase (alk-ATPase), acid ATPase (ac-ATPase)], morphometric and
      ultrastructural techniques. In PS-injected control groups, the gastrocnemius
      muscle of both sexes contained all the fibre types studied [slow-oxidative muscle
      fibres (type I), fast-oxidative glycolytic muscle fibres (type IIA) and fast
      glycolytic muscle fibres (type IIB)]. The type I fibres had the smallest
      diameter, type IIA had a medium diameter and type IIB fibres had the largest
      diameter. In OvO-injected groups, it was observed that the OvO had little effect
      on the gastrocnemius muscles of either sex, although there was significant
      enlargement of type IIB fibres. After the injection of OvOT, hypertrophy of
      muscle fibres was determined by morphometric study. The biggest increase in
      diameter was on type I fibres. In addition, degenerations on some mitochondria,
      accumulation of lipid droplets on type I and type II fibres, an increase in
      glycogen particles, bifurcation of myofibrils, an increase in the number and
      diameter of units resembling T tubules and an increase in ribosomal content were
      also observed in the same group by transmission electron microscope.
      Consequently, it was determined that testosterone can induce protein synthesis in
      gastrocnemius muscle fibres, and induces changes in shape and size, and also can
      change the appearance and the number of fibres.

PMID- 12797528
TI  - Immunohistochemical characterization of macrophage and dendritic cell
      subpopulations of the spleen, thymus, tongue and heart in cyclophosphamide
      induced immunosuppressed rat.
AB  - This study was undertaken to investigate the immunohistochemical characterization
      of different subpopulations of macrophages and dendritic cells (DCs) of the
      spleen, thymus, tongue and heart in cyclophosphamide (CY)-induced
      immunosuppressed rat. After CY treatment, remarkably, ED1+, ED2+ and ED3+
      macrophage subpopulations, in general exhibited signs of cellular activation such
      as an increase in number and size of cell, and an upregulation of the ED1, ED2
      and ED3 reactive surface molecule expression in all the organs studied, except
      for some macrophage subpopulations including ED1+ macrophages in the non-lymphoid
      tissues. Subpopulations of DCs showed a differential sensitivity to CY. Lymphoid
      DCs were more sensitive to CY than non-lymphoid interstitial DCs. CY induced a
      conspicuous upregulation of intercellular adhesion molecule-1 (ICAM-1) expression
      in the vascular endothelial cells, splenic marginal zone and thymic cortex. In
      this study, we demonstrated the in vivo effects of CY treatment on subpopulations
      of macrophages and DCs as well as on ICAM-1 expression in the rat spleen, thymus,
      tongue and heart. Moreover, our results shed more light on the activation effects
      of CY on certain subpopulations of macrophages, on the differential sensitivity
      of DCs to CY between the immature and mature ones, on the functional role of
      different subpopulations of macrophages, and on the significance of upregulated
      ICAM-1 expression in the splenic marginal zone and thymic cortex after CY
      treatment.

PMID- 12797530
TI  - [The occurrence of hemodynamic effective elements in the intestinal blood vessel
      system].
AB  - Arterioles, precapillary sphincters, capillary endothelium, and pericytes
      probably regulate the blood flow in the intestinal microvascular bed similar to
      other regions of the body because of their equipment with contractile filaments.
      Only throttle veins with their arrangement of pools and their characteristics
      probably exert influence on the hemodynamic qualities of the blood flow in the
      intestinal mucosa.

PMID- 12797529
TI  - Morphological relationship between intercalated duct and pancreatic islet in
      streptozotocin and/or camostat mesilate administrations in the chicken.
AB  - Present electron microscopical and immunocytochemistrical studies elucidated some
      morphological relationship between intercalated duct (ICD) and pancreatic islet
      cells in the chicken in streptozotocin (STZ) and/or camostat mesilate (CM)
      administrations. Twenty-one chickens were set into four experimental groups: (1)
      control group, (2) STZ administration group, (3) CM administration group, and (4)
      STZ + CM administration group. Cytoplasms of ICD cells stained more strongly with
      eosin in STZ administration group than other groups, and electron-dense materials
      and intercalated processes between ICD and islet cells were also increasing in
      time dependence in STZ administration. Number of pancreatic islet in STZ + CM co
      administration was about 3.1 times larger than other groups. Many small sized
      cells were detected at surrounding area of ICD and they incorporated 5-bromo-2'
      deoxyuridine better than other experimental groups. Present morphological data
      suggested that ICD cells might support some tolerances of pancreatic endocrine
      cells against toxic substances and also involve in regeneration of new pancreatic
      islet cells in STZ + CM co-administration.

PMID- 12797531
TI  - Incorporation of bovine bone marrow stromal cells into porcine foetal tissues
      after xenotransplantation.
AB  - Bovine bone marrow stromal cells (BMSCs) were injected into the liver of foetal
      pigs at about 40 days of gestation to test whether these cells could populate
      developing tissue, and if so, which ones. Approximately 40 days after injection,
      the foetuses were harvested and tissue sections from many areas of the body were
      analysed for the presence of bovine cells using two different methods. First,
      using PCR, bovine repetitive DNA was found to be present in DNA extracted from
      foetal pig tissues. Secondly, using oligonucleotide primed in situ synthesis
      (PRINS), the in situ presence of bovine cells was found within porcine tissue
      sections. PRINS-labelled cells were found within cartilage, perichondrium,
      connective tissue and smooth muscle. These data suggest that bovine BMSCs
      integrate throughout the foetal pig.

PMID- 12797532
TI  - Morphology of the small intestine of weaned piglets and a novel method for
      morphometric evaluation.
AB  - The intestinal morphology of 7-week-old pigs was investigated by light (LM) and
      scanning electron microscopy (SEM). The piglets were fed either a semisynthetic
      or a cereal-based diet. The shapes of the intestinal villi and crypts of the
      duodenum, jejunum and ileum were examined. The villi were predominantly tongue
      shaped. In the duodenum they were also ridged, branched and folded, and in the
      jejunum they were also leaf-like and ridged. At places with lymph follicles, the
      surface of the ileum was rugged with meandering fold-like villi. The crypts of
      the three segments of the small intestine were mainly coiled and sometimes
      branched. A novel morphometric evaluation method was introduced using the
      enlargement factors of each villus and crypt surface. The enlargement factor for
      the villus surface of the duodenum, jejunum and ileum was 3.13, 3.72 and 2.71,
      respectively. The factor for the crypt surface of the duodenum, jejunum and ileum
      was 9.07, 8.94 and 6.53, respectively. Furthermore, the relative proliferation
      rate and the epithelial renewal index were calculated for the first time. The
      relative proliferation rate of the duodenum, jejunum and ileum was 32.88, 34.78
      and 50.77 proliferations per mm crypt perimeter, respectively. The diets consumed
      had an influence on the epithelial renewal index being higher for piglets fed the
      cereal-based diets.

PMID- 12797533
TI  - Galanin-immunoreactive cells and their relation to calcitonin gene-related
      peptide-, substance P- and somatostatin-immunoreactive cells in rat lumbar dorsal
      root ganglia.
AB  - We report upon the distribution of galanin-immunoreactive (GAL-IR) cells in the
      lumbar dorsal root ganglia (DRG) of the rat, and upon the distribution of GAL-IR
      cells, which also contain calcitonin gene-related peptide (CGRP)-, substance P
      (SP)- and somatostatin (SOM)-immunoreactivity. Neuropeptide-immunoreactive lumbar
      DRG cells were 55.8% for CGRP, 12.7% for SP, and 6.5% for GAL in lumbar DRG
      cells. There was no significant difference between the right and left DRGs (L1
      L6) for any neuropeptide-immunoreactive cell (P < 0.01). In terms of size
      distribution, CGRP-immunoreactive cells were identified below 1500 microm2, and
      SP-, and GAL-IR cells below 600 microm2. Neuropeptide immunoreactive cells showed
      various immunoreactivities in the cytoplasm according to each neuropeptide. CGRP
      and SP immunoreactive cells were colocalized with GAL immunoreactive cells in the
      serial sections about 83.3 and 60% respectively, but SOM colocalizing with GAL-IR
      cells were not in evidence. The current results confirm and extend previous
      results, and show that neuropeptides can coexist in single sensory neurones of
      the rat DRG. In addition, our results demonstrate that the normal distribution of
      some neurotransmitters modulating sensory action in Wistar Kyoto rat, make this
      model more prone to develop neuropathic pain than Sprague-Dawley rat.

PMID- 12797534
TI  - Veins of the thoracic limb of the Van cat.
AB  - The drainage of the thoracic limb of the Van cat was performed by the superficial
      and deep vein systems. The superficial system was constituted by the cephalic
      vein and its branches. The deep vein system was constituted by the axillary vein
      and its branches. The two vein systems anastomosed with each other at various
      points along their courses. The cephalic vein emerged from the external jugular
      vein together with the superficial cervical vein. The axillary vein continued the
      subclavian vein. It ran caudoventrally and gave off the subscapular vein, at the
      level of the shoulder joint, then gave off two independent branches, which were
      the external thoracic veins. Then the rest of the vessel continued as the
      brachial vein. The thoracodorsal vein was formed by the communicate ramus vein
      which arose between the subscapular vein and the brachial vein. The cranial
      circumflex humeral vein arose double from the subscapular vein. One of them
      anastomosed with the deep brachial vein and the other one drained the biceps and
      the deep pectoral muscles. The cranial interosseous vein from the caudal aspects
      of the brachial vein and passed the interosseous space of the antebrachium then
      ran to the lateral aspect of the forearm. The caudal interosseous vein arose from
      the ulnar vein (in two specimens) and the median vein together with the ulnar
      vein (in two specimens) or independently from the median vein (in one specimen).
      Although many similarities were found in the veins of the thoracic limb of the
      Van cat as compared with the domestic cat, some significant differences were
      noted in the origin, course, anastomosing and ramification of veins of the
      thoracic limb.

PMID- 12797535
TI  - Arterial vascularization of the pineal gland in the fetus of Zavot-bred cattle.
AB  - This study aimed at revealing arterial vascularization of the pineal gland of the
      Zavot-bred foetus. Twenty foetuses, regardless of their sex, at the age of 2-7
      months were used. Coloured-latex was injected by way of both the right and left
      common carotid arteries. Then, dissection was performed and vessels nourishing
      the pineal gland were documented. The pineal gland is vascularized by a number of
      2-5 central rami. A small vessel arising from each of the central rami in two
      foetuses (10%) was shown anastomosing with a branch of the cranial cerebral
      artery, which advances in cranio-caudal direction in the callosal groove. Hence,
      anastomoses were observed between several sub-branches of each caudal cerebral
      and cranial cerebellar arteries.

PMID- 12797536
TI  - Ultra-structure of intracellular lipid vesicles of porcine GV-oocytes after in
      vitro fertilization and parthenogenetic activation.
AB  - The aim of our investigation was to compare the ultrastructure of lipid droplets
      in porcine pronuclear oocytes obtained after in vitro fertilization (IVF) or
      parthenogenetic activation (PGA) of Metaphase II (MII) oocytes. The
      ultrastructure of lipids in the IVF or PGA pronuclear oocytes after vitrification
      was also studied. There are two kinds of lipid droplets in porcine GV oocytes:
      'dark' and homogenous vesicles next to 'grey' vesicles with electron-lucent
      streaks. After IVF or PGA and following 16-h culture, only the presence of 'grey'
      vesicles was detected in IVF and PGA oocytes. Ultra-structure of lipid vesicles
      of PGA and IVF oocytes was similar. The PGA oocytes can be as model of the two
      pronuclear stage IVF oocytes.

PMID- 12797538
TI  - Increasing transplant mass results in long-term allograft survival and recovery
      from transplant vasculopathy.
AB  - Late allograft rejection due to transplant vasculopathy continues to be a major
      clinical problem. Increasing the ratio of donor transplant size to recipient
      weight has been shown to reduce the incidence of late allograft failure. Using a
      murine pancreas transplant model we have tested the hypothesis that increasing
      the donor transplant size in a recipient can promote long-term allograft survival
      by promoting recovery from transplant vasculopathy. Recipients of an allograft
      that showed extensive vasculopathy were transplanted with a second donor
      transplant. The effect of the second allograft on the vasculopathy present in the
      first graft was measured. Transplanting a second allograft reversed all signs of
      ongoing rejection, including transplant vasculopathy, resulting in long-term
      survival of the first graft. Vasculopathy was only reversed if the first and
      second grafts were from the same mouse strain, suggesting an antigen-specific
      mechanism. However, the recovery of the first graft was not associated with
      antigen-specific peripheral tolerance.

PMID- 12797540
TI  - Complex patterns of regulation of chemokine secretion by Th2-cytokines,
      dexamethasone, and PGE2 in tuberculous osteomyelitis.
AB  - Tuberculous osteomyelitis is characterized by uncontrolled inflammation leading
      to bone destruction. Chemokines recruit inflammatory cells but there are no data
      on the mechanisms limiting cell influx. We investigated the potential down
      regulators of chemokine secretion IL-4, IL-10, IL-13, dexamethasone, and PGE2, IL
      10 and IL-13 down-regulate M. tuberculosis-induced IL-8, IP-10, RANTES, and MCP-1
      secretion from MG-63 cells by between 48 and 94% (P < 0.05) but do not inhibit
      chemokine gene transcription. In contrast, IL-4 augments gene expression and
      secretion of IP-10 from 12,030 +/- 1070 to 24,330 +/- 1720 pg/ml/4 x 10(5) cells
      (P < 0.01) and RANTES secretion, from 3550 +/- 150 to 6930 +/- 400 pg/ml/4 x
      10(5) cells (P < 0.01). Dexamethasone and PGE2 caused a 13-fold down-regulation
      of secretion of all four chemokines but only dexamethasone inhibits mRNA
      accumulation. Data from primary osteoblasts were similar. In summary, down
      regulation of osteoblastic chemokine secretion was not uniformly observed and the
      control of chemokine secretion in response to M. tuberculosis is a complex
      process mediated by pre- and posttranscriptional mechanisms.

PMID- 12797539
TI  - Correlates of IL-10 and IL-12 concentrations in cervical secretions.
AB  - Interindividual variations in host immune responses to HPV infection are thought
      to be important determinants of viral persistence and progression to cervical
      intraepithelial neoplasia and cancer. However, few studies have measured local
      immune markers at the site of infection (e.g., the cervical mucosa). We sought to
      determine biologic correlates of IL-10 and IL-12 concentrations in cervical
      secretions. Cervical secretions were passively collected using a WeckCel sponge
      from 247 women participating in a natural history study of human papillomavirus
      infection as part of an immunologic ancillary study. IL-10 and IL-12
      concentrations were determined using standard ELISA assays. In general, IL-10 and
      IL-12 levels were significantly intercorrelated (Pearson's correlation
      coefficient = 0.6) but had somewhat different determinants. Significant increases
      (P < 0.05) in IL-10 concentrations were observed for nonovulatory phases of the
      menstrual cycle, postmenopausal status, recent use of oral contraceptives (OC),
      low secretion volume, macrolevels of heme contamination, and high vaginal pH.
      Increasing IL-10 levels were also observed among smokers, women with increasing
      numbers of lifetime sex partners, and women who report having less frequent sex
      (less than once per week), however, these results were not statistically
      significant. Significantly higher IL-12 concentrations were observed among recent
      OC users, women with low secretion volume, and women with a high vaginal pH.
      There was a non-statistically significant observation of increasing IL-12 levels
      among nonsmokers, women with increasing numbers of lifetime and recent
      pregnancies, and increasing levels of heme contamination. We failed to observe a
      significant association between HPV and IL-10 or IL-12 levels in this
      crosssectional sample. Future analyses of cervical cytokine levels and HPV
      infection should control for the inherent variation of local cytokine levels due
      to hormonal influences, hemoglobin contamination, pH, and cervical secretion
      volume differences.

PMID- 12797537
TI  - Cytokines and transcription factors that regulate T helper cell differentiation:
      new players and new insights.
AB  - The differentiation of naive CD4+ T cells into subsets of T helper cells is a
      pivotal process with major implications for host defense and the pathogenesis of
      immune-mediated diseases. Though the basic paradigm was discovered more than 15
      years ago, new discoveries continue to be made that offer fresh insights into the
      regulation of this process. T helper (TH)1 cells produce interferon (IFN)-gamma,
      promoting cell-mediated immunity and control of intracellular pathogens. We now
      know that TH1 differentiation is regulated by transcription factors such as T
      bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I
      IFNs, and IFN-gamma. In contrast, TH2 cells produce IL-4, which promotes allergic
      responses and is important in host defense against helminths. The transcription
      factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2
      differentiation. These key regulators of TH differentiation are the subject of
      this review.

PMID- 12797541
TI  - Role of mitogen-activated protein kinase pathways in the production of tumor
      necrosis factor-alpha, interleukin-10, and monocyte chemotactic protein-1 by
      Mycobacterium tuberculosis H37Rv-infected human monocytes.
AB  - The role of mitogen-activated protein kinase (MAPK) pathways in the secretion of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-8, and monocyte
      chemotactic protein-1 (MCP-1) was investigated in human monocytes that were
      infected with Mycobacterium tuberculosis H37Rv. Analysis of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) and p38 kinase showed rapid phosphorylation of
      both subfamilies in response to M. tuberculosis H37Rv. Using highly specific
      inhibitors of p38 (SB203580) and of MAPK kinase-1 (U0126 and PD98059), we found
      that both p38 and ERK were essential for M. tuberculosis H37Rv-induced TNF-alpha
      production, whereas activation of the p38 pathway, but not that of ERK, was
      essential for M. tuberculosis H37Rv-induced IL-10 production. Interestingly, the
      ERK pathway, but not that of p38, was critical for MCP-1 secretion from human
      monocytes that were infected with M. tuberculosis H37Rv. However, IL-8 secretion
      was not regulated by ERK1/2 or p38 MAPK. Collectively, these results suggest that
      induction of the MAPK pathway is required for the expression of TNF-alpha, IL-10,
      and MCP-1 by human monocytes during M. tuberculosis H37Rv infection.

PMID- 12797542
TI  - Innate immune responses in lupus-prone Palmerston North mice: differential
      responses to LPS and bacterial DNA/CpG oligonucleotides.
AB  - Inadequate immune response to infectious danger may contribute to the
      pathogenesis of systemic autoimmune diseases, e.g., systemic lupus erythematosus.
      To test this hypothesis, we studied innate responses of prediseased lupus-prone
      Palmerston North (PN) mice to lipopolysaccharide (LPS), bacterial DNA, and
      synthetic CpG oligonucleotides. LPS and bacterial DNA/CpG
      oligodeoxyribonucleotides (ODNs) drove PN splenocytes into the cell cycle and
      protected B cells against spontaneous apoptosis, as in control lupus-free DBA-1
      mice. LPS induced significantly higher IL-6 production in PN than in control
      splenocytes. In contrast, in PN splenocytes bacterial DNA and CpG ODNs induced
      approximately four- to sixfold lower IL-12p40 and approximately twofold lower IL
      6 secretion than controls. This reduction in cytokine secretion in PN mice was
      not due to delayed kinetics but was related to significantly higher constitutive
      and CpG-inducible IL-10 secretion. Neutralizing anti-IL-10 antibodies almost
      completely restored PN IL-6 and IL-12p40 secretion to DBA-1 levels, whereas
      exogenous IL-10 inhibited in vitro IL-6 and IL-12p40 production in DBA-1 mice.
      Importantly, treatment with either IL-10 or anti-IL-10 antibody did not modulate
      CpG-induced cell cycle entry and apoptosis protection in either strain. In
      conclusion, lupus-prone PN mice show abnormal innate responses through their
      pattern-recognition TLR9 receptors, characterized by higher inducible IL-10 and
      lower IL-12p40 and IL-6 secretion, thus implying that response to infectious
      danger in PN mice is inappropriate and may be linked to lupus pathogenesis.

PMID- 12797543
TI  - Immune response to influenza vaccination in an elderly population.
AB  - The purpose of this study was to assess the serum antibody responses to both the
      hemagglutinin and the neuraminidase antigens of inactivated influenza vaccine in
      45 elderly and 28 younger adults. After vaccination, antihemagglutinin antibody
      levels increased significantly and mean fold increases ranged from 2.8 to 22.0.
      Seroprotection rates were between 42.2 and 91.1% 1 month after vaccination and
      15.6 and 84.4% 5 months afterward. Seroresponse rates ranged from 42.2 to 91.1% 1
      month after vaccination and 15.6 to 82.2% 5 months afterward. After vaccination
      antineuraminidase antibody levels increased significantly and mean fold increases
      ranged from 3.6 to 12.3. Significantly higher antibody responses to both
      hemagglutinin and neuraminidase were observed for antigen A(H3N2) than for
      antigens A(H1N1) and B. In most instances there were no statistically significant
      differences between the elderly and the control subjects. Influenza vaccine was
      immunogenic in the institutionalized elderly, who developed good antibody
      responses to influenza hemagglutinin and neuraminidase antigens.

PMID- 12797544
TI  - HBcAg-specific CD8 T cells play an important role in virus suppression, and acute
      flare-up is associated with the expansion of activated memory T cells.
AB  - We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus
      (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27
      tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were
      divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)
      positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative
      patients with chronic HBV infection, and two HLA-A2-positive patients with acute
      HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27
      CD8Ts) were detected at a significantly higher prevalence in patients with anti
      HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of
      the total CD8 T cells. The prevalence was significantly higher in patients with
      HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV
      DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently
      higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in
      autologous peripheral blood lymphocytes. Longitudinal analysis of patients with
      acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT)
      was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis
      revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5,
      while those during low-ALT periods showed low expression. Furthermore, most liver
      infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective
      recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific
      CD8 T cells play an important role in the suppression of virus replication, and
      acute flare-up is associated with the expansion and activation of HBV-specific
      memory cells.

PMID- 12797545
TI  - Streptococcal cell wall induced arthritis: leukocyte activation in extra
      articular lymphoid tissue.
AB  - Rheumatoid arthritis (RA) is a common systemic inflammatory disease thought to be
      T-helper-1 cell driven, though current controversy involves the relative role of
      T cells versus other leukocytes. Thus, there is a need for better understanding
      of the role of various leukocytes and their subsets in RA. Using the
      streptococcal cell wall (SCW) induced arthritis model, we examined leukocytes
      isolated from peripheral blood, spleen, and lymph nodes using monoclonal
      antibodies directed against lineage specific cell surface markers. Activation
      status of these cells was assessed using CD44 and CD71 as markers. T cells in
      general, and CD4+ T cells in particular were found to be activated in spleen and
      lymph nodes. B cells and monocytes in spleen demonstrated increased activation as
      well. The activation of cells in the myeloid and lymphoid lineages in the chronic
      phase of arthritis indicates ongoing involvement of innate and cognate immunity.
      This study quantitates specific changes in B and T lymphocytes, and myeloid cells
      and is consistent with findings in human RA in which specific antibodies, T
      cells, and myeloid cells are all implicated in the pathogenesis of RA.

PMID- 12797546
TI  - Red blood cells stimulate human lung fibroblasts to secrete interleukin-8.
AB  - Following lung injury, red blood cells (RBC) may interact with extracellular
      matrix (ECM). Fibroblasts, the resident cell in the ECM, have the capacity to
      produce and secrete a variety of mediators including interleukin-8 (IL-8). In the
      present study we hypothesized that RBC, or soluble factors released from them,
      may stimulate IL-8 production by fibroblasts. Fibroblasts were cultured in a
      three-dimensional collagen gel culture system in the presence or absence of RBC
      or conditioned medium from RBC (RBC-CM). IL-8 release from fibroblasts was
      significantly increased when cultured with RBC or RBC-CM and both tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) further stimulated this
      IL-8 secretion. The enhanced production of IL-8 within fibroblasts was
      accompanied by increased IL-8 mRNA expression. To evaluate whether RBC-fibroblast
      interaction may lead to recruitment of neutrophils, a functional migration assay
      was performed. RBC and RBC-CM, in the presence of IL-1beta and TNF-alpha,
      increased the transmigration of neutrophils. Our results indicate that RBC, when
      interacting with ECM, may participate in the recruitment of inflammatory cells by
      stimulating fibroblasts to secrete IL-8. This might be an important mechanism
      regulating tissue repair after injury.

PMID- 12797547
TI  - The cox-2-specific inhibitor celecoxib inhibits adenylyl cyclase.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known causes of acute
      renal insufficiency and gastropathy in patients with chronic inflammatory
      diseases. This action is presumed to result from nonselective inhibition of both
      constitutive and inducible forms of prostaglandin H synthases, also known as the
      cyclooxygenase enzymes (i.e., COX-1 amd COX-2). Celecoxib (Celebrex) is a COX-2
      enzyme inhibitor and has emerged as a preferred therapeutic agent for the
      treatment of rheumatoid arthritis as compared to other NSAIDs. Celecoxib has
      recently been the subject of criticism for its side effects, mainly arterial
      thrombosis and renal hemorrhage, although it is considered a superior drug in
      protecting the gastrointestinal tract. In the present study, we report that
      celecoxib not only inhibited COX-2, but also exhibited the property of inhibiting
      adenylyl cyclase, an important enzyme forming the intracellular second messenger
      3',5'-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Celecoxib
      also inhibited cholera toxin-stimulated cAMP formation, which indicated its
      ability to permeate cell membranes in order to reach intracellular adenylyl
      cyclase. It inhibited in vitro adenylyl cyclase activity in both human colonic
      epithelial cells and purified adenylyl cyclase from Bordetella pertussis. The
      IC50 of celecoxib for B. pertussis adenylyl cyclase was calculated to be 0.375
      mM. Lineweaver-Burk analysis showed that the type of enzyme inhibition was
      competitive. The apparent Km and Vm of adenylyl cyclase was calculated as 25.0 nM
      and 7.14 nmol/min/mg, respectively. Celecoxib changed the Km value to 66.6 nM
      without affecting the Vmax. The current study suggests that apart from
      inflammation, celecoxib therapy could be further extended to diseases involving
      cAMP upregulation either by endogenous reactions or exogenous agents. These new
      data showing inhibition of adenylyl cyclase should be considered in light of the
      drug's pathological effects or in patients specifically excluded from treatment
      (e.g., asthmatics).

PMID- 12797548
TI  - Rho protein inhibition blocks cyclooxygenase-2 expression by proinflammatory
      mediators in endothelial cells.
AB  - Rho proteins participate in the regulation of inflammatory gene expression in
      endothelial cells. We made use of Clostridium difficile toxin B-10643 (TcdB
      10463) which inhibites RhoA/Rac1/Cdc42 to analyze their role in expression and
      regulation of cyclooxygenase-2 (COX-2) in endothelial cells (EC). Pretreatment of
      EC with TcdB-10643 prevented lipopolysaccharide (LPS)-or tumor necrosis factor
      alpha (TNFalpha)-related COX-2 expression but had no effect on COX-1 protein
      levels. TcdB-10463 preincubation suppressed LPS-dependent nuclear factor-kappaB
      activation (NF-kappaB). Rho inhibition did not affect COX-1 activity.
      Inactivation of Rho proteins before LPS stimulation blocked arachidonic acid (AA)
      , thrombin-, and Escherichia coli hemolysin (HlyA)-dependent release of COX-2
      related 6-ketoprostaglandin F(1alpha), (6k-PGF(1alpha)). In contrast, Rho
      inhibition did not affect COX-2-dependent 6k-PGF(1alpha) liberation when TcdB
      10643 was added 10 h after LPS or TNFalpha stimulation of EC. Therefore,
      RhoA/Rac1/Cdc42 contribute to NF-kappaB-dependent LPS- and TNFalpha-induced
      expression of PGHS-2 in EC but had no effect on the activity of expressed COX-1
      and COX-2.

PMID- 12797549
TI  - Parasympathetic modulation of local acute inflammation in murine submandibular
      glands.
AB  - The parasympathetic nervous system controls submandibular glands (SMG) functions
      in physiological and pathological conditions via muscarinic acetylcholine
      receptors (mAchR). We had previously demonstrated that IFNgamma and carbachol
      stimulate amylase secretion in normal murine SMG by mAchR activation. While the
      cytokine action depended on nitric oxide synthase activation, the effect of the
      agonist was mediated by prostaglandin E2 (PGE2) production. Both IFNgamma and
      carbachol triggered IFNgamma secretion in SMG. We here show that during local
      acute inflammation (LAI) induced by intraglandular injection of bacterial
      endotoxin, lypopolisaccharide (LPS), amylase secretion is decreased in comparison
      to control glands. We also observed that the muscarinic agonist carbachol
      stimulates in a dose-dependent manner amylase activity by M2 and M3 mAchR
      activation. Moreover, cyclooxygenase-2 (COX-2) activation and subsequent PGE2
      liberation, in a nitric oxide independent manner, seem to be involved in M3 and
      M2 receptor activation by carbachol. In contrast, the addition of exogenous
      IFNgamma or carbachol inhibits the cytokine liberation in LAI glands.

PMID- 12797551
TI  - When will east meet west?

PMID- 12797550
TI  - Blockade of integrin VLA-4 prevents inflammation and matrix metalloproteinase
      expression in a murine model of accelerated collagen-induced arthritis.
AB  - DBA/1LacJ mice were immunized with type II collagen and boosted with bacterial
      lipopolysaccharide (LPS) 17 days later to induce accelerated arthritis. Clinical
      signs of inflammation were observed as early as Day 20. Matrix metalloproteinases
      MMP-2, -3, -9, and -13, but not MMP-12, mRNA levels were increased on Day 24.
      Administration of anti-VLA-4 antibody (mAb; 8 mg/kg/day for 3 days) at the time
      of LPS treatment strikingly inhibited arthritis-induced paw inflammation and
      histological scores, but not the increase in MMP expression. A higher dose of mAb
      (20 mg/kg/day for 4 days) inhibited pathology and normalized the levels of MMP
      mRNAs. In conclusion, the pathophysiology of this accelerated model of arthritis
      is VLA-4-dependent, and VLA-4-mediated events have a role in inflammation-induced
      MMP expression. Inhibition of arthritis-induced increases in MMP expression is
      not necessary to reduce pathology. This model is well suited for identifying
      agents that block integrin VLA-4 in vivo.

PMID- 12797552
TI  - Beyond kerma--neutron data for biomedical applications.
AB  - Presently, many new applications of fast neutrons are emerging or under
      development, like dose effects due to cosmic-ray neutrons for airplane crew, fast
      neutron cancer therapy, studies of electronics failures induced by cosmic-ray
      neutrons, and accelerator-driven incineration of nuclear waste and energy
      production technologies. All these areas would benefit from improved neutron
      dosimetry. In this paper, the present rapid progress on measurements of double
      differential neutron-induced nuclear reaction data are described. With such data
      at hand, the full response of, in principle, any system, including human tissue,
      can be calculated in detail. This could potentially revolutionise our
      understanding of biological effects in tissue due to fast neutrons.

PMID- 12797553
TI  - Bayesian analysis of data: reconstruction of track structure at 100% detection
      efficiency for a track-nanodosimetric counter.
AB  - An algorithmic reconstruction of the probability distribution of ionisation
      cluster-size formation from measurements performed with detectors having a non
      uniform sensitive volume is presented. From such a data analysis, ionisation
      spectra, which correspond to a detection efficiency of 100% are extracted for the
      track-nanodosimetric counter at L.N.L.-I.N.F.N.

PMID- 12797554
TI  - Investigating the TEPC radiation quality factor response for low energy
      accelerator based clinical applications.
AB  - The use of a tissue equivalent proportional counter (TEPC) filled with propane
      based tissue equivalent gas simulating a 2 microm diameter tissue sphere has been
      investigated to estimate the radiation quality factor of the neutron fields used
      in in vivo neutron activation measurements at the McMaster University 3 MV Van de
      Graaff accelerator. The counter response to estimate the effective quality factor
      based on the definitions of Q(L) provided in ICRP 26 and 60 as a function of
      neutron energy has been examined experimentally using monoenergetic and
      continuous neutron spectra in the energy range of 35 to 600 keV. In agreement
      with other studies, the counter failed to provide a flat R(Q) response and showed
      a sharp drop below 200 keV neutron energy. Development of an algorithm to
      evaluate the quality factors using measured dose-mean lineal energy, yD, and
      comparison of the algorithm with other reported algorithms and analytical methods
      developed for the improvement in TEPC dose equivalent response has been reported.

PMID- 12797555
TI  - A study on radiographic repeat rate data of several hospitals in Jeddah.
AB  - Radiographic repeat rate data in diagnostic radiology in King Fahad Hospital
      (KFH), King Abdulaziz Hospital (KAH), and Maternity and Children Hospital (MCH)
      in Jeddah, Saudi Arabia, have been studied. The study provided valuable
      information to suggest preventive measures to reduce repeats. The variables
      included in the study are exposure techniques, examination types, total number of
      films used, number of films repeated, the film sizes, gender, the age groups of
      the patients, and reason for repetition. The total number of examinations in all
      three hospitals is 6001 using 8887 films on 5412 patients. The average repeat
      rate was 7.93%, where the individual hospital repeat rates were 9.57% in the MCH,
      7.84% in KAH, and 7.44% in KFH. The repeat rate for children and infants was
      found to be undesirable. The quality assurance (QA) programme can effectively
      reduce the unnecessary exposure and can identify the cause of the exposure. The
      overexposure, underexposure, and position fault were the foremost contributors
      for repeats and constitute 32.91%, 28.94%, and 22.98% of the total respectively.
      The QA study identified that human error and equipment malfunction are the major
      contributors to these causes of repeats. The highest repetition rate was for
      pelvis, 13.64%, followed by skull, 11.59%, and abdomen, 10.41%. It is estimated
      that the total area of wasted film in all three hospitals is 74.3 m2. As per the
      average repeat rate, the cost of repeat films in the entire kingdom per year has
      been projected to be about 1.82 million US dollars (SR 6.83 million) in the
      government hospitals only. Based on the findings of this study a set of
      recommendations have been prescribed for the radiology department to reduce the
      repeat rate and to improve the safety culture.

PMID- 12797556
TI  - Retrospective study of the iodine-131 contamination of workers in the
      radiopharmaceutical industry.
AB  - A dose reconstruction study was performed for personnel occupationally exposed to
      131I in radiopharmaceutical production, during the years 1981 to 1994, with the
      objective of estimating committed effective doses and critically reviewing the
      main causes of their exposures. The workers were selected from a group
      responsible for the production, labelling and distribution of all
      radiopharmaceutical material in Brazil. Best estimates of intakes and doses were
      derived from the examination of the individual monitoring records and the reports
      from the radiation protection supervisor, complemented by interviews with the
      workers and with radiation protection officers. Over this time period workers had
      chronic as well as acute intakes of 131I. Committed effective doses were found to
      be dependent on the task performed by the worker and the site of operation and
      inversely correlated with the amounts of iodine handled. Intakes in general were
      a consequence of inadequate radiation protection control.

PMID- 12797557
TI  - The specific absorbed dose constant: comparison of values published for 60Co
      photons.
AB  - For the specific absorbed dose constant for 60Co photons, three values quoted
      directly in the literature and two derived indirectly from published information
      are reported. The three publications giving the direct values mentioned no medium
      of absorption, whereas the other two specify tissue. A database of the specific
      absorbed dose constant is generated for each of 14 media namely air, water, bone
      and 11 types of soft tissue. These values are consistent with the three directly
      quoted values plus one of the indirectly obtained values. Air is found to be
      unlikely as the medium for the first three; and appropriate media for these are
      suggested. For the other two values, the generated database suggests that one is
      too small to be accurate; while the other is correct for tissue (as stated in the
      publication). An apparent error of 10(3) is identified in one of the values
      directly quoted.

PMID- 12797558
TI  - Thorium exposure during tungsten inert gas welding with thoriated tungsten
      electrodes.
AB  - The exposure to 232Th from TIG welding with thoriated electrodes has been
      determined at five different workshops. Welding with both alternating and direct
      current was investigated. The exposure levels of 232Th were generally below 10
      mBq m(-3) in the breathing zone of the welders. Two samples from AC welding
      showed significant higher exposure levels, probably due to maladjustment of the
      TIG welding power source. Samples of the respirable fraction of 232Th from
      grinding thoriated electrodes were also collected showing exposure levels of 5
      mBq m(-3) or lower. A dose estimate has been made for two scenarios, one
      realistic and one with conservative assumptions, showing that the annual
      committed effective dose from inhalation of 232Th, 230Th, 228Th and 228Ra, for a
      full-time TIG welder, in the realistic case is below 0.3 mSv and with
      conservative assumptions around 1 mSv or lower. The contribution from grinding
      electrodes was lower, 10 microSv or lower in the realistic case and 63 microSv or
      lower based on conservative assumptions. The study does not exclude occurrence of
      higher exposure levels under welding conditions different from those prevailing
      in this study.

PMID- 12797559
TI  - Quantification of low dose signal in EPR tooth dosimetry--a novel approach.
AB  - For radiation exposures below 100 mGy, the dosimetric signal in tooth enamel is
      too small to be measured by using the traditional dose reconstruction procedure.
      This is because low amplitude zero-added-dose signal can not be identified in an
      EPR spectrometer. A technique is presented wherein, zero-added-dose signal. when
      amplified by a proper known dose, can be measured in the EPR spectrometer.
      Mathematically, the accidental dose x is modified by a known amount of exposure,
      y (large enough so that the signal is now visible), and total exposure becomes x'
      = x + y, which is the modified-zero-added dose. The exposure x' is then
      quantified using the conventional backward extrapolation method and the
      accidental dose can be measured. In a laboratory controlled experiment, the
      feasibility of dose reconstruction in the 100 mGy range has been demonstrated.
      This may enable measurements of dose even due to suspected low exposure in tooth
      enamel.

PMID- 12797560
TI  - A combination study of indoor radon and in situ gamma spectrometry measurements
      in Greek dwellings.
AB  - The aim of the present study was to investigate of a possible correlation between
      indoor radon and indoor gamma dose rates deduced by in situ gamma spectrometry
      measurements by using a portable HPGe detector. Indoor radon and high resolution
      in situ gamma spectrometry measurements were performed in 60 apartments in
      Thessaloniki, the second largest city of Greece. Geometric mean radon
      concentration is 52 Bq m(-3). The mean total absorbed dose rate in air due to
      gamma radiation is 56 +/- 9 nGy h(-1). The contribution of the different
      radionuclides to the total indoor gamma dose rate in air is 41% due to 40K, 36%
      due to the thorium series and 23% due to the uranium series. No correlation was
      found between indoor gamma dose rate due to the uranium series and indoor radon
      for ground and first floor apartments. For upper floor apartments (above the
      second floor) a weak correlation is observed. The mean annual effective dose due
      to radon is 1.15 mSv, i.e., more than four times higher compared to the effective
      dose due to gamma radiation (0.27 mSv).

PMID- 12797561
TI  - Calibration of LR-115 for 222Rn monitoring taking into account the plateout
      effect.
AB  - The dose received by people exposed to indoor radon is mainly due to radon
      progeny. This fact points to the establishment of techniques that access either
      radon and progeny together, or only radon progeny concentration. In this work a
      low cost and easy to use methodology is presented to determine the total indoor
      alpha emission concentration. It is based on passive detection using LR-115 and
      CR-39 detectors, taking into account the plateout effect. A calibration of LR-115
      track density response was done by indoor exposure in controlled environments and
      dwellings, places where 222Rn and progeny concentration were measured with CR-39.
      The calibration factor obtained showed great dependence on the ambient condition:
      (0.69 +/- 0.04) cm for controlled environments and (0.43 +/- 0.03) cm for
      dwellings.

PMID- 12797562
TI  - A quick method for estimation of long-lived alpha activity in work atmospheres.
AB  - In an operating plant quick reporting of the status of long-lived alpha activity
      concentrations in the work atmosphere is required. This will help in taking any
      corrective control measures if required. Radon and thoron progeny concentrations
      prevalent in the general atmosphere predominantly interfere in measurement of
      long-lived alpha activity in air. The alpha counts due to radon and thoron
      progeny vary widely in many atmospheric conditions. Therefore, conventionally, 5
      days delay is allowed for all interfering activity to decay completely and true
      alpha air activity is then estimated. An approach for quick assessment of long
      lived alpha activity by eliminating interference due to radon and thoron progeny
      in air, is made here. Based on the study of the pattern of alpha count rate due
      to radon and thoron progeny in air, a method for estimation of long-lived alpha
      activity within 8 hours delay time is suggested in this paper.

PMID- 12797563
TI  - Influence of the Sonicare toothbrush on the structure and thickness of laboratory
      grown Streptococcus mutans biofilms.
AB  - PURPOSE: To evaluate the effect of powered brushing with the Sonicare electronic
      toothbrush on the structure and thickness reduction of S. mutans biofilms using
      digital time-lapse microscopy (DTLM) and confocal microscopy (CM) techniques.
      MATERIALS AND METHODS: S. mutans biofilms grown on glass microscope slides on BHI
      and 2% sucrose were exposed to Sonicare for 15 seconds with the bristle tips just
      contacting the slide, and at distances of 0.5, 1.0, and 1.5 mm above the slide.
      RESULTS: With direct bristle contact, the reduction in biofilm thickness was
      greater than 99%. DTLM showed the break up and detachment of biofilm caused by
      the shear forces generated by the rapid bristle motion in real time. The Sonicare
      was shown to significantly reduce biofilm thickness even when the bristles were 1
      mm above the biofilm. The percent biofilm thickness reduction was inversely
      proportional to the bristle distance. This study demonstrates the Sonicare
      toothbrush effectively removed biofilm from hard flat surfaces both by direct
      bristle contact and by fluid dynamic shear forces alone.

PMID- 12797564
TI  - Effects of lining materials on microleakage and internal voids of Class II resin
      based composite restorations.
AB  - PURPOSE: To evaluate the ability of various lining materials to reduce cervical
      marginal microleakage and internal voids within Class II resin-based composite
      restorations. MATERIALS AND METHODS: 168 extracted molars were prepared with both
      moderate and deep Class II cavities. The teeth were then randomly divided into 14
      groups and restored with direct composite or sandwich techniques using various
      lining materials [flowable composites, compomers and resin-modified glass-ionomer
      cements (RMGI)]. Following restoration, the teeth were stored for 24 hours,
      thermocycled, and placed in fuchsin dye for 24 hours. Subsequently, the teeth
      were sectioned in halves and observed through a stereomicroscope. Cervical
      microleakage and internal voids were assessed separately as the length ratio of
      dye penetration to the cervical wall and the area ratio of voids to sectioned
      restorations. The data were analyzed with one-way ANOVA. RESULTS: Flowable
      composite lining groups demonstrated either similar or more cervical microleakage
      than did their respective direct restoration groups. Groups lined with RMGIs
      showed similar or better marginal sealing than did their resin restoration
      groups. In deep cavities, Vivaglass Liner group showed the best marginal sealing.
      RMGI-lined groups exhibited more internal voids in deep restorations.

PMID- 12797566
TI  - Cavity preparation by Er-YAG laser on pulpal temperature rise.
AB  - PURPOSE: To measure the intrapulpal temperature changes in vitro, during cavity
      preparation and caries removal, using the Opus 20 Er-YAG laser plotted as a
      function of the laser energy and pulse rate. MATERIALS AND METHODS: Class I and V
      cavity preparations were made in 175 fresh extracted caries-free human teeth and
      caries removal was carried out in 42 carious extracted teeth by the Opus 20 Er
      YAG laser. K-type thermocouples were inserted into the pulp chambers filled with
      heat conducting paste. Lasing was carried out at different irradiation energies
      and pulse frequencies, using air-water spray. Temperature changes in the pulp
      chamber were measured during lasing. RESULTS: In all groups tested, the maximum
      temperature rise was lower than 5.5 degrees C, which is considered as critical
      value for pulp vitality. The highest temperature values were measured during Cl I
      preparations (3.13 degrees C +/- 1.54 - 4.11 degrees C +/- 1.29), medium values
      were in Cl V in enamel (2.38 degrees C +/- 1.37 - 4 degrees C +/- 1.07) and the
      lowest were in cementum (2.10 degrees C +/- 0.61 - 3.61 degrees C +/- 1.15) and
      during caries removal (1.21 degrees C +/- 0.46 - 3.51 degrees C +/- 0.68).

PMID- 12797565
TI  - Effect of fluoridated dentifrice and acidulated phosphate fluoride application on
      early artificial carious lesions.
AB  - PURPOSE: To evaluate the effect of a combination of fluoride dentifrice and
      acidulated phosphate fluoride (APF) on enamel with incipient caries lesions.
      MATERIALS AND METHODS: Bovine dental enamel blocks with artificial caries lesions
      were divided into four treatment groups and submitted to a pH-cycling model: (1)
      Placebo non-fluoridated dentifrice (PD); (2) Fluoridated dentifrice (FD), 1,100
      ppm F; (3) APF (12,300 ppm F, pH 3.5) + PD; 4) APF+FD. APF was applied to enamel
      blocks of groups APF+PD and APF+FD before the pH-cycling regimen and all of them
      were exposed to dentifrice during the cycling. RESULTS: The results showed that
      61-81% of the fluoride previously deposited in enamel by APF was released to the
      media during the pH-cycling. The final concentration of fluoride in enamel in the
      group APF+PD was lower than that before the cycling (P < 0.05), but in the group
      APF+FD the reduction was not significant (P> 0.05). FD treatment was
      significantly more efficient than PD in rehardening the enamel surface and
      increasing the hardness of the caries lesions. APF+PD treatment was not more
      efficient than PD in increasing enamel hardness and an additive effect of APF+FD
      was not observed.

PMID- 12797567
TI  - Effect of three concentrations of sodium fluoride dentifrices on clinical caries.
AB  - PURPOSE: To assess whether the anti-caries effectiveness of three concentrations
      of fluoride dentifrice (placebo, 500 ppm F- and 1450 ppm F-) could be
      differentiated with small sample sizes in short time frames. MATERIALS AND
      METHODS: A controlled fluoride (F) dose-response study was conducted in
      concurrence with a supervised school oral hygiene regimen to assess whether
      dentifrices with increasing fluoride levels could be differentiated with small
      sample sizes in short time frames. The study was a randomized, double-blind study
      conducted for a period of 21 months. Subjects (N = 657 with approximately 219 per
      group) were randomized to placebo dentifrice, 500 ppm F- dentifrice or 1450 ppm F
      dentifrice treatments for the first 9 months of the study. Subjects in the
      placebo group were then switched to either 500 ppm F- or 1450 ppm F- dentifrice
      for the remainder of the study, while subjects in the fluoride groups continued
      with their original treatment assignments. A calibrated examiner measured visual
      tactile caries as DMFS that was supplemented with a radiographic examination at
      baseline, 9 months and 21 months for each subject. RESULTS: The mean caries
      increments at 9 months were 0.35 surfaces, 0.34 surfaces, and 1.28 surfaces for
      the 1450 ppm F-, 500 ppm F-, and placebo groups, respectively. The mean caries
      increments at 21 months were 0.21 surfaces, 0.26 surfaces, 1.75 surfaces and 1.90
      surfaces for the 1450 ppm F-, 500 ppm F-, placebo/1450 ppm F-, and placebo/500
      ppm F- groups, respectively. The 500 ppm F- and 1450 ppm F- fluoride dentifrices
      delivered statistically significantly (P< 0.05) lower DMFS scores than the
      placebo control dentifrice at 9 months, while at 21 months the 500 ppm F- and
      1450 ppm F- fluoride dentifrices delivered statistically significantly lower DMFS
      scores as compared to the both the placebo/500 ppm F- and the placebo/1450 ppm F-
      dentifrice groups. There was no evidence of a dose response (1450 ppm F- < 500
      ppm F-) at 9 months or at 21 months. In this study, the effectiveness of the two
      fluoride dentifrices was observed at 9 months and these outcomes were still
      present at 21 months, confirming that caries benefits can be observed in time
      frames as short as 9 months with approximately 200 subjects per treatment group.

PMID- 12797568
TI  - Sealing ability of dentin coating using adhesive resin systems.
AB  - PURPOSE: To assess the sealing ability of dentin coating using adhesive resin
      systems to verify its potential in protecting the dentin/pulp from the oral
      environmental stimuli. MATERIALS AND METHODS: 15 extracted human premolars were
      prepared for complete crowns and the electrical resistance of their coronal
      dentin was measured. The prepared teeth were then randomly divided into three
      groups, and the prepared dentin surface of five teeth in each group was coated
      using one of three adhesive resin systems (All-Bond 2, Clearfil Liner Bond II,
      Super-Bond D-Liner) with low viscosity resins. Measurements for electrical
      resistance of the prepared coronal dentin was repeated after the first and second
      coat of the low viscosity resins, and at 1 and 4 weeks of storage in a
      physiological saline solution. Additionally, three prepared teeth were exposed to
      either cold (37 degrees C --> 4 degrees C) or heat (37 degrees C --> 60 degrees
      C) stimulus and the temperature change was monitored inside the pulp chamber.
      Time-temperature curve was obtained before and after the first and the second
      dentin coating. RESULTS: Before dentin coating electrical resistance of the
      coronal dentin ranged from 1 to 11 k(omega), and increased significantly after
      the first coating by 3-15 times, and by 5-185 times after the second coating.
      Thermal diffusion was significantly smaller in the dentin after the coating.
      Before coating, the temperature change inside the pulp chamber ranged from 2-5
      degrees C at 5 seconds after the thermal stimuli were applied. This decreased
      significantly to between 0.3-0.5 degrees C after the coating.

PMID- 12797569
TI  - Dentin permeability and eugenol diffusion after full crown preparation.
AB  - PURPOSE: To compare teeth prepared to receive a metallic versus a metal-ceramic
      crown with respect to (1) in vitro dentin permeability before and after using a
      desensitizing agent and (2) pulpal eugenol concentration after sealing a
      temporary crown with a zinc oxide-eugenol based cement. MATERIALS AND METHODS:
      The roots of 20 human mandibular molars were separated and the crowns were
      prepared to receive a metallic crown. The hydraulic conductance was recorded
      before and after using Protect dentin desensitizer. The crowns were then further
      reduced to receive a metal-ceramic crown and the hydraulic conductance was
      recorded under the same conditions, on deeper dentin, before and after using the
      desensitizing agent. Twenty additional teeth were prepared: 10 to receive a
      metallic crown and 10 teeth to receive a metal-ceramic crown. A tube filled with
      1 mL phosphate buffered saline (PBS) was sealed to the cementoenamel junction. A
      temporary crown was sealed onto the preparation with Temp Bond. The amount of
      eugenol that diffused across dentin into PBS was spectrofluorimetrically measured
      at Day 1 and Day 7. The crown preparations were vertically sectioned and the
      dentin remaining thickness was recorded. RESULTS: The hydraulic conductance of
      teeth prepared for a metal-ceramic crown was twice as high as teeth prepared for
      a metallic crown (P < 0.001). The desensitizing agent reduced the hydraulic
      conductance in both groups (P< 0.001). The two groups showed the same hydraulic
      conductance after using Protect (ns). No significant difference was found in the
      amount of eugenol diffusion between the two groups of teeth although eugenol
      diffusion decreased with time (P < 0.01). No correlation was found between
      eugenol diffusion and remaining dentin thickness.

PMID- 12797570
TI  - Influence of different softstart polymerization techniques on marginal adaptation
      of Class V restorations.
AB  - PURPOSE: To investigate the influence of different curing methods used to achieve
      softstart polymerization on the marginal adaptation of a resin-based composite in
      Class V restoration. MATERIALS AND METHODS: Class V cavities, with the gingival
      wall located 1 mm below the cemento-enamel junction, were prepared on buccal and
      lingual surface of 80 extracted premolar teeth. The teeth were randomly divided
      into 8 groups of 10 teeth. The cavities were restored with a combination of resin
      based composite (Z100) and adhesive (Single Bond) in different softstart
      polymerization techniques or placement techniques. Softstart-polymerization
      obtained from either softstart mode (Elipar Highlight) or the modified methods
      using standard curing unit (Spectrum 900 and XL3000), bulk or incremental filling
      techniques were also used. After thermocycling between 5 degrees C and 55 degrees
      C for 500 cycles, the specimens were immersed in 2% methylene blue dye at 37
      degrees C for 6 hours. Longitudinal sections of the specimens were scored for
      marginal dye penetration under the microscope. Kruskal-Wallis and Mann-Whitney
      tests were used for statistical analysis. RESULTS: There was no statistically
      significant difference of dye penetration among techniques at enamel or dentin
      margins (P > 0.05). Dye penetration observed at dentin margins was significantly
      higher than that observed at enamel margins (P < 0.05) except for the group
      restored with a combination of incremental technique and softstart-polymerization
      using Spectrum curing unit. There was no statistically significant difference of
      microleakage between buccal and lingual cavities at enamel or dentin margins (P >
      0.05).

PMID- 12797571
TI  - Factors that affect the shear bond strength of multiple component and single
      bottle adhesives to dentin.
AB  - PURPOSE: To examine the effects of thermocycling and the long-term integrity of
      the bonds between adhesive and resin composite to bovine dentin using multi-step
      and single bottle adhesive systems. MATERIALS AND METHODS: Dentin bonding sites
      were prepared using water irrigated #600 grit SiC paper on bovine incisor crowns
      mounted in acrylic resin. A 4 mm diameter area of dentin was etched, rinsed, left
      visibly moist and adhesives applied according to the manufacturers' instructions.
      The adhesives were: Scotchbond Multipurpose, Single Bond, All Bond 2, One Step,
      and Prime & Bond 2.1. Cylinders of Z100 resin composite 4 mm in diameter were
      positioned over the adhesive and visible light-cured. Bonded specimens were
      divided into five groups each containing 12 samples and: (1) stored in water for
      24 hours; (2) stored in water for 7 days; (3) stored in water for 270 days; (4)
      thermocycled after 24 hours and stored for a total lapsed time of 7 days; (5)
      stored in water for 6.5 days, and thermocycled for a total lapsed time of 7 days.
      All storage temperatures were 37 degrees C. All specimens were shear (SBS) tested
      to failure at the end of each storage period, the results converted to MPa and
      the mode of fracture failure recorded. RESULTS: The SBS for all five adhesives
      deteriorated over time; the effects of thermocycling were shown to be variable
      and dependant upon the adhesive; the modes of fracture failure were shown to be
      adhesive/cohesive or mixed; after long-term (270 days) storage there was an
      increased tendency for adhesive/cohesive fracture failure.

PMID- 12797572
TI  - Cytotoxicity of dentin conditioners and primers on human periodontal ligament
      cells in vitro.
AB  - PURPOSE: To examine the cytotoxicity of dentin conditioners and primers on human
      periodontal ligament (PDL) cells in vitro. MATERIALS AND METHODS: Primary PDL
      cells were plated in 96 well culture plates and exposed to 100 microL of test
      solutions. Undiluted Cavity Conditioner (CC), Vitremer Primer (VP), Uni-Etch
      (UE), All-Bond 2 (AB), Gluma conditioner (GC), and Gluma primer (GP) were
      examined at full strength and at 1/100 and 1/1000 dilutions in culture medium.
      Cytotoxicity of the undiluted material was determined immediately following
      exposure of the cells to the test substance. Cytotoxicity of the diluted
      materials was determined immediately following a 300-second exposure of the cells
      to the test solution, as well as 24 hours after removal of the test solution.
      Cytotoxicity was expressed as lactate dehydrogenase activity retained within the
      cells following exposure divided by the activity in unexposed control cells.
      RESULTS: Exposure to each undiluted test substance resulted in severe damage to
      the cells (78.2-100%). At 1/100 dilution, only exposure to UE resulted in
      significant cytotoxicity (72.9%) immediately following removal of the solution.
      But significant cytotoxicity (21-100%) was evident in cells 24 hours after
      removal of each of the materials. At 1/1000 dilution, exposure to UE (14.8%) and
      GP (27.2%) resulted in mild cytotoxicity. Twenty-four hours after removal of the
      solutions, there was a mild but significant cytotoxic effect of each of the test
      substances (18.5-49.4%).

PMID- 12797573
TI  - Effect of light source direction and restoration thickness on tensile strength of
      a dual-curable resin cement to copy-milled ceramic.
AB  - PURPOSE: To evaluate the effects of exposure duration and source direction on
      bond strength of a dual-curable resin cement to copy-milled ceramic MATERIALS AND
      METHODS: Ceramic blocks (Vita Celay Blanks) were cut into 1 mm, 2 mm and 3 mm
      thick slices. Following silanization (Tokuso Ceramic Primer), the slices were
      bonded using dual-cure resin cement (Bistite II) and subjected to one of four
      photo-curing strategies: no light-cure (control), 20 seconds light-cure from one
      direction, 120 seconds from one direction, and 20 seconds from each of six
      directions. After 24-hour water storage at 37 degrees C, the microtensile bond
      strengths and resin cement Knoop Hardness of the bonded specimens were
      determined. The data were analyzed using two-way ANOVA and Fisher's PLSD test at
      a confidence level of 95%. Specimen failure modes were determined using a laser
      scanning confocal microscope. RESULTS: The KHN of the control group was
      significantly lower than those of the light-cured groups (P < 0.05). There were
      no significant differences in bond strength and microhardness when the 1 and 2 mm
      thick ceramic slices were light-cured for either 120 seconds from one direction,
      or for 20 seconds from six directions (P > 0.05). However, when ceramic thickness
      increased from 2 to 3 mm, significant reduction in bond strength occurred when
      light-cure was applied for 120 seconds from one direction, but not when applied
      for 20 seconds each from six directions (P < 0.05).

PMID- 12797574
TI  - Treatment of cervical sensitivity with a root sealant.
AB  - PURPOSE: To assess a novel root sealant for cervical sensitivity. MATERIALS AND
      METHODS: Clinical assessments, impressions and modified USPHS criteria (n = 24)
      were carried out at baseline, 3, 6 and 19 months. Plaque samplings were performed
      at baseline and after 3 and 19 months. RESULTS: At 19 months, 20 patients
      completed the clinical trial. There was a significant reduction for the
      sensitivity scores. The log10 of total colony-forming units (cfu + 1) from
      overlying plaque significantly reduced. The percentage of mutans streptococci
      reduced after 3 months (P < 0.01) and yeasts also reduced after 19 months (P <
      0.01). The mean overall wear (+/- SD) (microm) on the sealant was 78.8 +/- 21.3
      at 3 months; 95.4 +/- 7.3 after 6 months and 136.5 +/- 9.8 after 19 months. In
      conclusion, this sealant was capable of reducing sensitivity. Further wear on the
      cervical surface was prevented as the mean sealant thickness was 65.3 +/- 3.3
      after 19 months.

PMID- 12797575
TI  - Polymerization contraction stresses of resin-based composite restorations within
      beveled cavity preparations of Class I restorations.
AB  - PURPOSE: To evaluate internal stresses resulting from polymerization of resin
      based composite materials in cavity preparations beveled at the internal line
      angles or the cavosurface margin, compared with those in conventional butt-joint
      box-shaped cavity preparations. MATERIALS AND METHODS: Contraction stress
      generated in resin-based composite restorations placed in an experimental cavity
      preparation model was determined using micro-photoelastic analysis. Three types
      of cavity preparations simulating Class I restorations with bevels at internal
      line angles (1 mm and 2 mm deep), and at the cavosurface margin (2 mm deep) were
      prepared in a posterior composite model in order to obtain no marginal defect
      with the restorative composite. The transparent restorative composite was bulk
      filled into the preparations and light-cured for 80 seconds. Specimens 2 mm thick
      for micro-photoelastic analysis were cut perpendicular to the long axis of the
      preparation. Fringe patterns for directions and magnitudes of stresses were
      obtained using transmitted and reflected polarized light. Then, the photoelastic
      stress analysis was performed to examine stresses in the preparations. The data
      were statistically compared with the previous data in conventional butt-joint box
      shaped preparations by ANOVA and Scheffe's F test (P < 0.05). RESULTS: In 1 and 2
      mm deep internal beveled cavity preparations, the maximum principal stress lines
      were parallel to the wall at the straight internal bevels. In the preparation
      with a round bevel at the cavosurface margin, the stress distribution in the bulk
      of the preparation was similar to that in the butt-joint preparation. Maximum
      stress values in 1 and 2 mm deep internal beveled preparations were 12.2 +/- 0.2
      MPa and 18.8 +/- 2.8 MPa, respectively. For 2 mm-deep preparation, the maximum
      stress values in the internal beveled preparations were significantly lower than
      those values in butt-joint box-shaped cavity preparations. Maximum stress values
      in the preparations with the bevel at the cavosurface margin were 22.7 +/- 1.0
      MPa, and were not significantly different from those values observed in the butt
      joint preparations.

PMID- 12797576
TI  - Effect of low body temperature during unilateral labyrinthectomy on vestibular
      compensation in the guinea pig.
AB  - OBJECTIVES: Vestibular compensation, the recovery that follows unilateral
      vestibular deafferentation (UVD), is a model for central nervous system
      plasticity. Recovery from the static symptoms of UVD may involve temperature
      dependent processes that modulate the immediate effects of UVD and/or the
      capability of the central nervous system to undergo adaptive plasticity. In this
      study we investigated changes in oculomotor and postural vestibular symptoms
      resulting from low body temperature during UVD. MATERIAL AND METHODS: To study
      the effect of low temperatures at the time of UVD on vestibular compensation, we
      compared the rate of compensation and peak values for postural [roll head tilt
      (RHT) and yaw head tilt (YHT)] and oculomotor [spontaneous nystagmus (SN)]
      symptoms in three groups of guinea pigs. Animals in Group 1 (n = 6) were
      maintained at 38 degrees C throughout unilateral labyrinthectomy (UL). Animals in
      Group 2 (n = 6) were not temperature-controlled and animals in Group 3 (n = 4)
      were cooled with ice to 25 degrees C throughout UL. RESULTS: Cooled animals
      showed significantly higher rates of SN upon recovery from anaesthesia and took a
      significantly longer time to compensate. Cooled animals were also slower to
      compensate for postural symptoms (RHT and YHT), with 2 animals showing no
      compensation for RHT 52 h after UL. CONCLUSION: Hypothermia (25 degrees C) during
      UVD surgery exacerbates postural and oculomotor symptoms following UL and
      significantly slows recovery.

PMID- 12797577
TI  - Estimation of perilymph concentration of agents applied to the round window
      membrane by microdialysis.
AB  - OBJECTIVE: The round window membrane (RWM) is known to be permeable to various
      biological substances. Application of biological substances to the RWM has been
      shown to affect inner ear fluid composition and damage hair cells, resulting in
      functional changes RWM instillation of gentamicin, a preferentially
      vestibulotoxic aminoglycoside, is used as a therapeutic treatment for patients
      with intractable vertigo and is gaining acceptance as a chemical vestibular
      ablation agent, despite considerable variations in the incidence and severity of
      hearing loss associated with gentamicin. Clearly, the susceptibility of
      vestibular and auditory hair cells to the ototoxic effects of gentamicin is not
      well understood. The aim of this study was to understand the kinetics of urea and
      methylene blue instilled into the inner ear space through the RWM and to
      establish a method for determining the optimal dosage for the treatment of inner
      ear disorders. MATERIAL AND METHODS: We used inner ear microdialysis to quantify
      changes in perilymph concentration of low molecular weight agents applied to the
      RWM in a chinchilla model. RESULTS: Preliminary results after placement of a
      microdialysis probe and application of a low molecular weight marker (urea) to
      the RWM were extrapolated from a time versus concentration plot from dialysates
      sampled over a 3-min interval using modifications of standard microdialysis
      equations for estimation of in vivo recovery. Our data suggest that inner ear
      microdialysis can be used to measure the pharmacokinetics of a low molecular
      weight agent within the perilymphatic space without the need for repeated direct
      sampling. CONCLUSION: Inner ear microdialysis may be a useful method for
      establishing a therapeutic dosage for ototoxic agents used in the treatment of
      inner ear disorders.

PMID- 12797578
TI  - Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin
      ototoxicity.
AB  - OBJECTIVE: Apoptosis may play an important role in the mechanism of
      aminoglycoside ototoxicity. Caspases and calpains are regarded to be important
      factors in the regulation of cell death in the inner ear. We hypothesized that
      caspase or calpain inhibitors would protect hair cells from aminoglycoside
      ototoxicity. MATERIAL AND METHODS: In order to test this hypothesis we carried
      out a pilot study to determine if gentamicin (GM) would induce caspase and
      calpain immunolabeling in guinea pig hair cells Having confirmed this we carried
      out the main experiment using guinea pig vestibular organ culture to determine if
      caspase and calpain would protect the hair cells from GM ototoxicity. RESULTS:
      Immunoreactivity for caspase-3 and m-calpain was detected in the vestibular
      sensory cells and ganglia after GM treatment. Both caspase and calpain inhibitors
      protected hair cells against gentamicin ototoxicity. CONCLUSION: It is suggested
      that inhibition of apoptosis is essential in order to block aminoglycoside
      ototoxicity.

PMID- 12797579
TI  - Retinoic acid depletion induces keratinizing squamous differentiation in human
      middle ear epithelial cell cultures.
AB  - OBJECTIVE: The pathogenesis of cholesteatoma behind an intact tympanic membrane
      remains controversial. Squamous metaplasia of the middle ear mucosa is thought to
      be a possible mechanism in such cases. However, to date, no definitive
      experimental results have proved this association. This study was undertaken to
      investigate whether normal human middle ear epithelial (NHMEE) cells undergo
      keratinizing squamous differentiation in a retinoic acid (RA)-deficient culture.
      MATERIAL AND METHODS: We examined the morphological differences between RA
      deficient and -sufficient cultures, and determined the expressions of the mucin
      gene and cornifin-alpha mRNAs as indicators of mucous and squamous
      differentiation, respectively. RESULTS: Histomorphologically, the NHMEE cells
      differentiated into a keratinizing squamous epithelium in RA-deficient cultures.
      In addition, the expressions of mucin gene 5AC (MUCSAC) and MUC8 mRNAs were
      suppressed, and the expression of cornifin-alpha mRNA increased progressively as
      a function of differentiation in RA-deficient cultures. CONCLUSIONS: This study
      shows that RA depletion induces keratinizing squamous differentiation in NHMEE
      cell cultures. This finding supports the hypothesis that middle ear cholesteatoma
      originates from metaplastic middle ear mucosa.

PMID- 12797580
TI  - The effect of optical devices and repeated trials on the velocity of saccadic eye
      movements.
AB  - OBJECTIVE: The purpose of this prospective study was to analyze the effect of
      glasses and contact lenses on the latency and velocity of visually evoked
      saccadic eye movements. MATERIAL AND METHODS: A saccadic test was performed 10
      times on 20 emmetropic controls (Group A) and 20 ametropic test subjects with
      myopia (Group B) who were using glasses (Subgroup Bg) or contact lenses (Subgroup
      Bc). RESULTS: No training or fatigue effect on either latency or eye velocity was
      registered. Regardless of visual acuity (Group A or B) or of the optical device
      used (Subgroup Bg or Bc), no significant intergroup difference in latency could
      ultimately be established. Subgroup Bc showed a significantly slower eye velocity
      than Group A. Regardless of the optical device used, subjects with a higher
      degree of myopia (> 6 D) showed a lower eye velocity than the Group A controls.
      Additionally, saccadic velocity was lower in this subgroup ( > 6 D) in subjects
      using contact lenses than in those using glasses. CONCLUSION: These results
      demonstrate that optical devices have an influence on the
      electronystagmographical analyses of the vestibulo-ocular reflex that must be
      taken into consideration, particularly in scientific investigations.

PMID- 12797582
TI  - Oral versus i.v. administration of the glycerol test: side-effects and
      usefulness.
AB  - OBJECTIVE: To compare two methods of performing the glycerol test. MATERIAL AND
      METHODS: Glycerol was given orally and intravenously to 12 patients suspected of
      having Meniere's disease. RESULTS: Glycerol given orally at a dose of 0.51 g/kg
      produced a change of > 10 mOsm/kg in all 12 patients while glycerol given
      intravenously at a dose of 0.30 g/kg produced the same change in osmolality in
      only 1/12 patients. The results of the tests were similar in 10 cases using the
      Klockhoff criteria and in 8 cases using the Snyder criteria. Positive test
      results after oral compared to i.v. administration occurred in four and two
      cases, respectively using the Klockhoff criteria and in six and eight cases,
      respectively using the Snyder criteria. The amount of discomfort was consistently
      higher, with one exception, when glycerol was given orally rather than
      intravenously. CONCLUSION: The glycerol test using the Snyder criteria probably
      yields most additional diagnostic information when the patient fulfils the
      clinical criteria of possible or probable Meniere's disease.

PMID- 12797581
TI  - High-resolution CT findings suggest a developmental abnormality underlying
      superior canal dehiscence syndrome.
AB  - OBJECTIVE: Patients with superior canal dehiscence (SCD) syndrome experience
      vertigo and oscillopsia with loud sounds and/or stimuli that result in changes in
      middle ear or intracranial pressure. Findings on temporal bone CT were analyzed
      to determine if a developmental abnormality is associated with the syndrome.
      MATERIAL AND METHODS: Temporal bone CT scans [0.5 mm collimation and projections
      into the superior semicircular canal (SC) plane] were used to compare the bone
      overlying the SC in patients with SCD syndrome (20 unilateral, 7 bilateral) and
      in 88 patients without SCD syndrome who had undergone temporal bone CT for
      evaluation of other otologic disorders (controls). RESULTS: The thickness of bone
      overlying the SC in the controls measured 0.67 +/- 0.38 mm (mean +/- SD). For
      individual control subjects. the thickness of bone on one side was correlated
      with that on the other side (r = 0.43; p < 0.0001). The thickness of bone
      overlying the SC on the intact side in patients with unilateral dehiscence
      measured 0.31 +/- 0.23 mm, and was thinner than that noted in the controls (p <
      0.0001). CONCLUSION: These findings support the notion that there is a
      developmental abnormality underlying SCD syndrome. When dehiscence is found on
      one side, the contralateral side is likely to be thin.

PMID- 12797583
TI  - Experimentally induced motion sickness in fish: possible role of the otolith
      organs.
AB  - OBJECTIVE: Although the occurrence of motion sickness is largely attributed to
      sensory conflict, the reasons for the highly variable inter-individual
      susceptibility to motion sickness remain unclear. One cause may be asymmetry
      between otoconial masses in the right and left inner ear. This hypothesis has
      been supported by experiments in fish under conditions of prolonged
      weightlessness and parabolic flight. In swordtail fish (Xiphophorus helleri) we
      examined the extent to which a Coriolis force environment, which has a strong
      motion sickness-triggering effect, disturbs swimming behaviour or produces motion
      sickness. MATERIAL AND METHODS: In a sealed aquarium, fish (n = 22) were
      subjected to Coriolis stimulation by constant vertical axis rotation, combined
      with pendular oscillation around a horizontal axis. RESULTS: Initially, at low
      stimulus intensity, all fish showed active compensatory swimming behaviour.
      However, while the majority (n = 19) maintained active compensation movements at
      higher stimulus levels, the others (n = 3) entered a passive uncoordinated state,
      from which they recovered again after reduction of stimulus intensity. On
      examination of the otoconial mass, we found asymmetries between the right and
      left utricles in all three cases and between the saccules in one case.
      CONCLUSION: We conclude that a lateral preponderance of the otoconial masses in
      the utricle or saccule promotes motion sickness under experimental conditions.
      The utricle appears to play a more important role in this than the saccule.

PMID- 12797584
TI  - Variables affecting speech perception in postlingually deaf adults following
      cochlear implantation.
AB  - OBJECTIVE: To evaluate the time span over which there is greatest improvement in
      postlingually deaf adults undergoing cochlear implantation. Additionally, to
      quantify potential patient and device factors that may predict the postoperative
      results. MATERIAL AND METHODS: A longitudinal study was conducted. Numbers,
      monosyllables and sentence test results were collected for 66 cochlear implant
      subjects [Combi 40/40 +, n = 60; Clarion HF2, n = 2; Nucleus 24m/k, n = 4] at
      regular intervals for up to 6 years following cochlear implantation. RESULTS: All
      patients showed a steady improvement over time on all tests. Progress during the
      first 12 months was statistically significant, with further improvements being
      recorded after the 12-month testing period. The duration of deafness and the
      number of electrodes (8 for the Combi 40, 12 for the Combi 40 + ) appeared to be
      weakly correlated with postoperative performance. Re-implantation after device
      failure had no negative effect on speech reception. Subjects who were "upgraded"
      from an analogue to a digital cochlear implant improved their test results almost
      twofold. CONCLUSION: All the patients in our study gained substantial benefit
      from their cochlear implants. It is encouraging to note that the factors examined
      were not deemed to be relevant predictors of performance. Even long-term deaf
      subjects and re-implantees are able to achieve an excellent level of speech
      perception.

PMID- 12797585
TI  - Impact of tumor size on hearing outcome and facial function with the middle fossa
      approach for acoustic neuroma: a meta-analytic study.
AB  - OBJECTIVE: The purpose of this study was to review the English language
      literature concerning the effect of tumor size on hearing outcome and facial
      function after the middle fossa approach for acoustic neuroma in a large patient
      population. MATERIAL AND METHODS: The literature search identified a total of 11
      studies reporting hearing outcome and facial function for a given tumor size.
      There were 1073 and 797 cases available for the analysis of hearing outcome and
      facial function, respectively. These cases were subdivided based on the way in
      which tumor size was measured: category 1 considered only the extracanalicular
      portion of the tumor; and category 2 considered the largest diameter of the
      tumor. In category 1, hearing and facial results were regrouped based on tumor
      size as follows: intracanalicular (IC) tumors; 1-9 mm tumors; 10-20 mm tumors;
      and a combined group of < 0.5 mm tumors, including IC tumors. In category 2,
      tumors were subdivided into 2 groups: those < 10 mm in diameter; and those 10-20
      mm in diameter. In each category, tumor size groups were compared using the chi2
      test in terms of the rate of functional hearing preservation and good facial
      function. RESULTS: In category 1, analysis of the rate of functional hearing
      preservation showed that IC tumors compared favorably with the 1-9 mm and 10-19
      mm tumors (56.9% vs 45.6%, p = 0.016; and 56.9% vs 32.3%, p < 0.001,
      respectively). The IC tumor group had the best rate of good facial function,
      followed by the 1-9 mm and 10-19 mm tumors (98.9% vs 93.9%, p = 0.007: and 98.9%
      vs 85.6%, p < 0.001, respectively). In category 2, rates of functional hearing
      preservation and good facial function were almost the same for tumors < 10 mm in
      diameter and those 10-20 mm in diameter (p > 0.05). CONCLUSIONS: The meta
      analysis revealed that tumor size is an important variable determining hearing
      outcome and facial function. Inclusion of the IC portion of a tumor in the tumor
      size measurement apparently hampered the statistical power of the study, leading
      to an overestimation of the size of IC tumors.

PMID- 12797586
TI  - Results of vestibular autorotation testing at the end of intratympanic gentamicin
      treatment for Meniere's disease.
AB  - OBJECTIVE: The vestibular autorotation test (VAT) examines the ocular response to
      voluntary horizontal and vertical head movements at frequencies for which the
      vestibular system is the main source for eye stabilization. The purpose of this
      study was to analyse the VAT results in patients with disabling Meniere's disease
      and to evaluate the change in VAT values once treatment with intratympanic
      gentamicin had terminated and clinical signs of vestibular hypofunction could be
      observed. MATERIAL AND METHODS: The 30 study subjects were patients diagnosed
      with definitive unilateral Meniere's disease that could not be controlled with
      medication. The vestibulo-ocular reflexes of each patient were evaluated by means
      of the VAT before the first injection of gentamicin and after the last injection.
      RESULTS: The pattern of abnormalities found in this population conformed to the
      selection criteria and the findings reflected a severe disabling process, with
      major modifications in the vestibulo-ocular reflex. At the end of treatment there
      was a reduction in the peak frequency of head oscillation. Furthermore, we
      commonly found that, in the horizontal VAT, gain and phase were reduced while in
      the vertical VAT some subjects registered a normal response. The phase in the
      horizontal and vertical VATs was most significantly reduced for oscillation
      frequencies of 2-3.7 Hz. CONCLUSION: This study provides further evidence that
      effective control of vertigo in patients with Meniere's disease can be achieved
      by administering intratympanic gentamicin.

PMID- 12797587
TI  - Model experiment of benign paroxysmal positional vertigo mechanism using the
      whole membranous labyrinth.
AB  - Whole membranous labyrinths of bullfrogs were used in order to replicate the
      human vestibule. The posterior semicircular canals (PSCs) were exposed, leaving
      the remaining membranous labyrinth encapsulated in the otic capsule. Vibration
      was applied to the surface of the bony capsule using a conventional surgical
      drill in order to dislodge the otoconia from the utricle. The position of the
      preparation was controlled so that the dislodged otoconia were attached to the
      cupular surface. This was regarded as a cupulolithiasis model. The action
      potentials changed instantaneously according to the gravitational force on the
      cupula. When the otoconia were dislodged and held within the PSC lumen, the
      position of the whole preparation was changed so that the otoconia moved back and
      forth within the canal lumen. This is a model of canalolithiasis. The action
      potentials changed in combination with the otoconial movement after a latent
      period. Both cupulolithiasis and canalolithasis are potentially valid mechanisms
      of benign paroxysmal positional vertigo (BPPV). However, canalolithiasis is the
      most likely mechanism of BPPV, which is usually characterized by nystagmus of
      short duration and long latency. A vibratory stimulus was able to detach the
      otoconia from the utricle, suggesting that mechanical insult could be a possible
      etiology of BPPV.

PMID- 12797588
TI  - Hypoxia in paranasal sinuses of patients with chronic sinusitis with or without
      the complication of nasal allergy.
AB  - OBJECTIVE: In order to elucidate the pathogenesis of the radiologic opacity of
      the sinuses frequently observed in patients with allergic rhinitis, the
      mechanisms underlying their sinus mucosal swelling were studied clinically.
      MATERIAL AND METHODS: We confirmed the presence of hypoxia in inflamed sinuses
      and obstruction of the sinus ostium in operated patients with chronic sinusitis
      by digitally monitoring the oxygen tension. The possibility of radiologic sinus
      shadow was also investigated after transient obstruction of the natural ostium.
      RESULTS: The oxygen tension was significantly lower in inflamed than non-inflamed
      sinuses (p < 0.01), irrespective of the presence or absence of allergic rhinitis.
      In 54.5% of patients without sinusitis, transient obstruction of the middle
      meatus by gauze packing resulted in the appearance of a pathologic sinus shadow
      on radiograms obtained after septoplasty and turbinotomy. In both allergic and
      non-allergic rhinitis, thick opacity was the most frequently encountered pattern
      (p < 0.01). CONCLUSION: Our study revealed that in the absence of a primary
      allergic reaction in the sinus mucosa, blocking of the middle meatus and ostium
      by allergic swelling of the nasal mucosa may induce hypoxia and secondary mucosal
      swelling in the sinuses.

PMID- 12797589
TI  - Tumor necrosis factor increases MUC1 mRNA in cultured human nasal epithelial
      cells.
AB  - OBJECTIVE: Mucins are high molecular weight glycoproteins which are normally
      expressed on the surface of a variety of epithelia. It is possible that shedding
      of such molecules from the epithelium could play a role in preventing bacterial
      colonization at the mucosal surface. Immunohistochemical and reverse
      transcriptase polymerase chain reaction(RT-PCR) analyses of human inferior
      turbinates have shown the existence of MUC1 mucin in nasal mucosa. However, the
      regulatory mechanisms of MUC1 mucin are poorly understood. In order to clarify
      the modulation of mucin gene expression, we developed a real-time semi
      quantitative RT-PCR based on TaqMan fluorescence methodology to quantify MUC1
      mRNA in primary cultured human nasal epithelial cells (HNECs). MATERIAL AND
      METHODS: HNECs were stimulated with recombinant human tumor necrosis factor (TNF)
      alpha (20 pg/ml to 20 ng/ml) for specified time periods (0, 12, 24 and 48 h) and
      MUC1 mRNA was determined by means of semi-quantitative RT-PCR. RESULTS:
      Significant increases in MUC1 gene expression in HNECs were initially detected at
      12 h, peaking at 24 h after stimulation. TNF-mediated MUCI mRNA expression at 24
      h was significantly inhibited by co-incubation with human recombinant soluble TNF
      receptor. CONCLUSIONS: TNF-mediated MUC1 gene expression may contribute to the
      pathogenesis of human inflammatory upper airway disorders. Also, our mucin mRNA
      real-time PCR provides a quantitative method for investigating the regulation of
      mucin gene expression in both healthy and diseased samples.

PMID- 12797591
TI  - Coinfection by multiple strains of Epstein-Barr virus in infectious mononucleosis
      in immunocompetent patients.
AB  - OBJECTIVE: A molecular study of Epstein-Barr virus (EBV)-induced infectious
      mononucleosis (IM) was performed. The presence of a 30-bp deletion on the latent
      membrane protein-1 (LMP-1) oncogene from EBV in Caucasian IM patients was
      evaluated. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained
      from 27 IM patients and 18 adenoids, 28 tonsils and 16 EBV-related reactive
      lymphadenitis specimens were used as controls. DNA isolation, EBV polymerase
      chain reaction (PCR) and LMP-1 oncogene PCR analysis were performed. RESULTS: The
      30-bp deletion on LMP-1 was identified in 29.6% of IM patients, but was always
      seen in conjunction with full-length LMP-1. Although the LMP-1-deleted strain
      seemed to be more prevalent in IM (29.6%) and EBV-related reactive lymphadenitis
      (37.5%,) than in adenoid (0%) or tonsil specimens (21.4%), these differences were
      not significant (p > 0.05; chi2). Thus, a 30-bp deletion on LMP-1 was present in
      almost a third of Caucasian IM patients. CONCLUSION: The finding of coinfections
      in IM patients confirms that primary infection by more than one EBV strain is
      possible.

PMID- 12797590
TI  - Complications of temperature-controlled radiofrequency volumetric tissue
      reduction for sleep-disordered breathing.
AB  - OBJECTIVE: Temperature-controlled radiofrequency volumetric tissue reduction
      (RFVTR) is a minimally invasive technique used in the treatment of the tongue
      base, soft palate and turbinates. Complications seem to be rare, but the scope of
      previous studies was often limited by the small number of patients included. The
      aim of this study was to evaluate postoperative complications in a large series
      of patients. MATERIAL AND METHODS: In this retrospective study, temperature
      controlled radiofrequency procedures (Somnoplasty) performed between May 1998 and
      March 2002 were considered. The charts of the patients were analyzed with regard
      to intra- or postoperative complications. RESULTS: In total, 322 patients
      received 497 treatment sessions; 239 of these treatments were isolated and the
      remaining 258 were combined procedures. Mean follow-up was 122.8 +/- 145.5 days.
      Concerning radiofrequency surgery, nine postoperative complications were observed
      (2.0%) as follows: ulcerations of the tongue base or soft palate; dysphagia
      necessitating hospital admission; temporary palsy of the hypoglossal nerve; and
      an abscess of the base of the tongue. CONCLUSIONS: Complications occurring after
      RFVTR are infrequent and mostly mild. Overall, temperature-controlled RFVTR is a
      safe procedure when used both in isolation and as part of a combined approach.

PMID- 12797592
TI  - Influence of the Provox Flush, blowing and imitated coughing on voice prosthetic
      biofilms in vitro.
AB  - OBJECTIVE: This study investigates the effect of regular airflow, as an isolated
      single factor, through Groningen and Provox2 voice prostheses on biofilm
      formation. MATERIAL AND METHODS: Groningen and Provox2 voice prostheses were
      placed in a modified Robbins device and inoculated with the total microflora from
      an explanted Groningen voice prosthesis. After 3 days, prostheses were either
      flushed 3 times per day with the Provox flush, treated with an airflow using an
      increasing order of air pressure (10, 15 and 20 cmH2O) or vigorously perfused by
      means of imitated coughing (air pressure 20 cmH2O). As a control, prostheses were
      left undisturbed to promote biofilm growth. Following flushing, blowing or
      coughing, each artificial throat was perfused with 200 ml of phosphate-buffered
      saline. This procedure was repeated three times a day for 9 days. At the end of
      each day, the artificial throats were filled with growth medium for 30 min and
      left empty during the night after draining. After 12 days the microflora on each
      voice prosthesis was quantified by plating on blood agar for bacteria and on de
      Man, Rogosa and Sharpe agar for yeasts. RESULTS: The use of the Provox flush
      reduced bacterial prevalence on Groningen and Provox2 voice prostheses to 71% and
      45% of the control values, respectively, without affecting the number of yeasts.
      Increasing airflows and imitated coughing yielded reductions of 45-70% in
      bacterial and yeast prevalence on Provox2 voice prostheses. On the Groningen
      voice prostheses the effects of increasing airflows and imitated coughing were
      less pronounced: reductions in bacterial and yeast prevalence of 56-87% were
      observed. CONCLUSION: This study shows that use of the Provox flush has a
      cleansing effect, especially on Provox2 voice prostheses, and furthermore
      suggests that daily airflow through voice prostheses as part of a daily
      maintenance scheme reduces biofilm formation and can be expected to prolong the
      life of these devices.

PMID- 12797593
TI  - Histological study of experimental reconstructive materials for repair of lateral
      skull base and dura mater defects in dogs.
AB  - OBJECTIVE: In order to assess the reconstructive properties of fascia lata,
      superficial fascia lata and bone morphogenetic protein (BMP) in skull base
      surgery, lateral skull base bone and dura mater defect models were established in
      dogs MATERIAL AND METHODS: As a repair material we selected fascia lata, either
      alone or in combination with BMP, for reconstructing large cranial defects in
      dogs. Twenty dogs undergoing a 3.0 x 4.0 cm2 full-thickness excision of the
      parietal bone were divided into four equal groups as follows: fascia lata
      reconstruction; fascia lata reconstruction plus BMP; controls; and fascia lata
      reconstruction plus BMP with direct exposure of fascia lata. The implants were
      harvested at 2-15 weeks and examined histologically. Results-Treated and
      untreated implants were quite different: formation of new bone occurred in the
      dogs treated with BMP whereas the unreconstructed controls demonstrated only a
      bridge of fibrovascular connective tissue. CONCLUSION: The results of this study
      suggest that it is better to combine BMP and reconstructive material for the
      treatment of bone defects.

PMID- 12797594
TI  - Hoarseness caused by unilateral vocal fold paralysis: how long should one delay
      phonosurgery?
AB  - We present a case of idiopathic right vocal fold paralysis which resolved
      completely 18 months after onset. Instead of using surgery to improve the
      hoarseness of our patient, our experience suggested that speech therapy might be
      effective. Although the voice can be improved by overadduction of the healthy
      vocal fold, as surgery is irreversible it is better to wait for 18 months after
      onset in case spontaneous recovery occurs. During this period, one should of
      course continue to investigate the origin of the paralysis.

PMID- 12797595
TI  - The effect of methylenetetrahydrofolate reductase C677T common variant on
      hypertensive risk is not solely explained by increased plasma homocysteine
      values.
AB  - The C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene causes a
      moderate increase in total plasma homocysteine (tHcy). We studied the effect of
      MTHFR TT homozygosity and mild hyperhomocysteinemia on arterial hypertension.
      Normotensive controls (n = 223) and hypertensive subjects (n = 235) were matched
      for age, gender, and history of cardiovascular disease. Homocysteine levels were
      measured by a polarization immunoassay method. Methylenetetrahydrofolate
      reductase we determined by polymerase chain reaction and restriction fragment
      analysis. Hypertensives showed elevated tHcy compared to normotensive group in
      men (P = 0.039). Homocysteine values higher than 15 micromol/L were associated
      with increased hypertensive risk in the male population [odds ratios (OR) = 1.63;
      95% confidence interval (CI) = 1.06-2.52; P = 0.027]. In multivariate analysis,
      TT genotype was associated with an increased risk of hypertension in males (OR =
      2.27; 95% CI = 1.12-4.60; P = 0.022) An increased hypertensive risk was observed
      in those TT males with tHcy levels higher than 15 micromol/L (OR = 2.78; 95% CI =
      1.05-7.3; P = 0.032) but not in those non-TT males with tHcy levels higher than
      15 micromol/L (P = 0.33). Our findings do not support the possibility that mild
      hyperhomocysteinemia my solely account for the hypertensive risk associated to
      the TT genotype.

PMID- 12797596
TI  - Fenoldopam treatment improves peripheral insulin sensitivity and renal function
      in STZ-induced type 2 diabetic rats.
AB  - Dopamine and diabetes mellitus are reported to have close link between them. We
      have studied the effect of six-week treatment with D1 receptor agonist fenoldopam
      (1 mg/kg, i.p., daily) on glucose, lipid, and renal profile in streptozotocin
      (STZ)-induced (non-insulin dependent) type 2 diabetic rats. Streptozotocin (90
      mg/kg, i.p.) was injected to two day old Sprague-Dawley pups. Streptozotocin
      produced hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, increase
      in serum urea and creatinine by the time animals were 10 week old. Treatment with
      fenoldopam significantly decreased serum glucose, insulin, cholesterol,
      triglyceride, urea, creatinine, and blood pressure. During oral glucose tolerance
      test (OGTT), diabetic rats showed increase in AUC(glucose) and AUC(insulin).
      Fenoldopam significantly decreased AUC(glucose) in diabetic rats. Diabetic rats
      showed lower insulin sensitivity index (K(TTT)) that was significantly increased
      by treatment with fenoldopam in diabetic rats. Diabetic rats showed decrease in
      urinary sodium. Fenoldopam treatment significantly increased urine output as well
      as urinary sodium indicating reduced sodium retention. Our data indicates
      fenoldopam treatment improves peripheral insulin sensitivity and renal function
      in STZ-induced type 2 diabetic rats.

PMID- 12797597
TI  - Functional effects of acute coronary occlusion and catecholinergic stimuli on the
      isolated normothermic hemoperfused porcine heart.
AB  - The aim of this study was to characterize functional parameters in the isolated
      and normothermic hemoperfused porcine beating heart model after
      pathophysiological stimuli for extended perfusion periods. Hearts were prepared
      and connected to a specially developed perfusion equipment, which simultaneously
      allowed perfusion with warm autologous blood as well as blood dialysis. Two
      groups were established: group A (12 hearts: no intervention) and group B (6
      hearts: occlusion of the ramus circumflexus of the left coronary artery for 2
      hours). Blood gas analyses and oxymetry were performed at baseline and every 30
      min during a 6 hours perfusion period. Coronary perfusion pressure (CPP) and
      blood flow (CBF), right and left ventricular pressure, blood and dialyzate pH
      values, and temperature were monitored online by a microcontroller. A steady
      state regarding the CPP and the CBF was achieved after 1 hour of perfusion for
      both groups. In group B, CPP increased during occlusion. Comparison of both
      groups showed no significant differences in the bicarbonate and sodium levels in
      blood and dialyzate. The potassium concentration in blood and dialyzate increased
      in both groups constantly during the experiments. No clear alteration of the
      oxygen consumption was observed. Lactate levels in blood and dialyzate increased
      during occlusion as did the aspartataminotransferase (AST) venous levels (both
      determined only for group B). Four concentrations of norepinephrine were injected
      into the stem of the coronary arteries (10, 20, 40, 80 microg). A clear inotropic
      effect of this hormone on right and left ventricular pressure was observed. It
      was concluded that longer perfusion periods and simulation of myocardial
      infarction for a clinically relevant period can be performed using this model. In
      addition, right and left ventricular function appear to be well preserved in this
      model, since the isolated porcine heart responded to norepinephrine stimuli.

PMID- 12797599
TI  - Diminished expression of constitutive nitric oxide synthases in the kidney of
      spontaneously hypertensive rat.
AB  - In kidney, nitric oxide (NO) synthesized by nitric oxide synthase (NOS) regulates
      sodium and water excretion, and renal medullary blood flow. The expression of
      constitutive NOS, endothelial NOS (eNOS) and neuronal NOS (nNOS), were assessed
      in kidney of the spontaneously hypertensive rat (SHR) and the normotensive Wistar
      Kyoto (WKY) rat by Western blot analysis and immunocytochemistry. Neuronal NOS
      expression was observed in the cortex and eNOS was detected only in theinner
      medulla of both WKY and SHR. In SHR, expression of eNOS was attenuated to 35.1 +/
      10.8%, while expression of nNOS was only 57.5 +/- 5.7% of the levels seen in WKY
      rat. Immunocytochemical studies revealed decreased staining of nNOS in the macula
      densa, collecting ducts and in the glomerulus of SHR compared to WKY rat.
      Endothelial NOS immunoreactivity was restricted to vascular structures of the
      inner intima cells and smooth muscle cells, and was markedly reduced in the
      vasculature of SHR. The decreased renal blood flow observed in SHR may be linked
      to a diminished expression of eNOS and nNOS, underscoring the importance of these
      enzymes in the pathophysiology and maintenance of genetic hypertension.

PMID- 12797598
TI  - Influence of plasma insulin levels on antinatriuretic and vasoconstrictor actions
      of angiotensin-II.
AB  - The objective of the present study is to investigate whether plasma insulin
      levels play a role in the antinatriuretic and vasoconstrictor actions of
      angiotensin-II (Ang-II). We evaluated antinatriuretic function of endogenous Ang
      II using an AT1 receptor antagonist, candesartan in anesthetized Sprague-Dawley
      rats. In control rats, candesartan produced significant increases in natriuresis
      and diuresis and these effects were abolished in streptozocin (STZ, 55 mg/kg
      i.p.) treated rats. Replacement of insulin restored these renal effects of
      candesartan. In a separate group of rats pretreated with an autonomic ganglionic
      blocker, pressor responses to Ang-II and norepinephrine (NE) before or after L
      NNA, a nitric oxide synthase inhibitor were not affected by STZ treatment.
      However, insulin replacement greatly augmented these responses. These data
      provide evidence in vivo showing that insulin can enhance both antinatriuretic
      and vasoconstrictor actions of Ang-II. Hence exaggerated renal and vascular
      effects of Ang-II in the obese Zucker rats observed in our previous studies may
      be related to hyperinsulimemia and this phenomena could contribute to salt
      sensitivity and development of sustained hypertension.

PMID- 12797600
TI  - Fundamentals of multichannel CT.
AB  - Multichannel CT has become a very valuable tool in diagnostic imaging. It
      provides a combination of fast and long coverage in conjunction with thin slices.
      The fast scanning allows for single-breathhold scanning, fewer motion artifacts,
      and better use of intravenous contrast media. The brains of the MCCT scanners are
      the sophisticated detector arrays packed with electronics to handle the flow of
      image information. The submillimeter detectors rows offer isotropic properties to
      the image voxels, thereby creating viewing in any plane and better three
      dimensional renderings.

PMID- 12797601
TI  - Multiplanar and three-dimensional imaging of the thorax.
AB  - Although axial images are sufficient for diagnosis in most instances, knowledge
      of multiplanar imaging techniques is essential to apply them in appropriate
      circumstances. In particular, appropriately applied multiplanar imaging adds
      confidence to interpretations and assists surgeons and bronchoscopists in
      planning procedures. The need for multiplanar imaging must be assessed before
      performing any study so that the image acquisition parameters allow for suitable
      reformations.

PMID- 12797602
TI  - Multidetector-row CT of the heart.
AB  - Despite worldwide efforts aimed at primary and secondary prevention, heart
      disease is still the leading cause of death in the western world. There is great
      interest in developing tools for noninvasive assessment of the presence and
      degree of coronary artery disease. The advent of multidetector-row CT allows high
      resolution volume coverage of the entire thorax and motion-free imaging of the
      heart and adjacent vessels within one breathhold. An exciting application with
      significant potential for cardiac risk stratification, which may overcome the
      obvious limitations of coronary calcium imaging in the future, is the use of the
      cross-sectional nature of contrast-enhanced multidetector-row CT coronary
      angiography for assessment of total coronary artery plaque burden.

PMID- 12797603
TI  - Pulmonary embolus imaging with multislice CT.
AB  - Multiple data support the concept that single-slice and multislice CT have
      fundamentally modified the diagnostic approach of patients with suspected PE.
      Although the definitive role of spiral CT angiography in the diagnostic algorithm
      has yet to be determined, it is clear that CT angiography has numerous advantages
      compared with other diagnostic tests. Bearing in mind that an effective
      diagnostic strategy should be as flexible as possible to be applied in every
      clinical setting, the role of spiral CT angiography in the diagnostic algorithm
      has to be considered among several practical parameters, such as the experience
      of the attending physician, degree of severity of the patient's clinical
      condition, the availability of diagnostic equipment, and specific logistics.

PMID- 12797604
TI  - Thoracic aorta imaging with multisclice CT.
AB  - Multislice CT aortography represents a major advance in the noninvasive
      evaluation of thoracic aortic disease. MSTCA is rapidly becoming the preferred
      modality for the initial investigation of acute aortic syndromes. Although scan
      quality is usually excellent, special attention to various technical parameters
      is required to optimize image quality. Familiarity with diagnostic pitfalls and
      the common imaging presentations of various thoracic aortic syndromes is
      necessary for accurate diagnosis.

PMID- 12797605
TI  - Thoracic venous anatomy multidetector row CT evaluation.
AB  - Two-dimensional CT angiography provides much information of the systemic and
      pulmonary thoracic veins. The combination of MDCT and volume-rendering techniques
      postprocessing provides higher-quality data sets and a method fully to harness
      the potential for image display and interpretation. Although this may not
      radically alter sensitivity for detection of systemic or pulmonary venous
      pathology it does provide a more comprehensive and sophisticated evaluation
      through volume acquisition and interpretation.

PMID- 12797606
TI  - Multislice helical CT of the central airways.
AB  - Multislice helical CT has revolutionized the non-invasive evaluation of the
      central airways with CT. The quick speed of image acquisition afforded by MSCT
      improves the quality of end-inspiration images and has expanded the ability to
      assess the airway during dynamic exhalation. Furthermore, the improved quality of
      multiplanar and three-dimensional images provided by MSCT has ushered in an
      exciting era of alternative methods of viewing CT data that are more visually
      accessible and often more anatomically meaningful. At present, the author
      routinely obtains multiplanar reformation and three-dimensional images for
      assessment of a variety of central airway abnormalities, including airway
      stenoses and webs, complex airway diseases, extrinsic airway compression,
      tracheobronchomalacia, and poststent placement. Further advances in CT
      technology, data processing, and image display, and increased clinical experience
      with advanced imaging reconstruction methods, will likely further expand the role
      of multiplanar and three-dimensional reconstruction images in the assessment of a
      wide variety of central airways disorders in the near future.

PMID- 12797607
TI  - Lung nodule detection and characterization with multislice CT.
AB  - The ability to identify and characterize pulmonary nodules has been dramatically
      increased by the introduction of multislice CT (MSCT) technology. Using high
      resolution sections, MSCT allows considerable improvement in assessing nodule
      morphology, enhancement patterns, and growth. MSCT also has facilitated the
      development and potential of clinical application of computer-assisted diagnosis.

PMID- 12797608
TI  - Multislice CT in thoracic trauma.
AB  - The introduction of CT imaging in the 1970s revolutionized all aspects of medical
      care, perhaps nowhere more so than in the evaluation of acutely injured patients.
      Just as single-slice helical scanning was a great advance over conventional CT,
      the capabilities of MSCT are proving to be dramatically superior to single-slice
      methods. Improved contrast bolus imaging, thinner slices, and isotropic voxels
      should enable the trauma radiologist to identify both major organ system
      disruption and subtle injuries more promptly. Multiplanar and three-dimensional
      reconstructions, a forte of MSCT, facilitate rapid communication of disease
      states with surgeons and others involved in the care of injured patients. In many
      centers, whole-body CT is beginning to supplant plain films of the chest and
      spine in the evaluation of severe trauma victims; the cost-effectiveness of such
      methods is still under evaluation.

PMID- 12797609
TI  - Paddle-wheel multislice helical CT display of pulmonary vessels and other lung
      structures.
AB  - The authors have now instituted the paddle-wheel method of CT reconstruction
      imaging of the lungs as a routine supplement to the standard axial multislice
      helical CT pulmonary angiography images for pulmonary embolism, and are exploring
      its role in other diseases. This unique way of viewing lung structures adds a new
      dimension to pulmonary imaging. Large-scale comparison studies of the traditional
      and the proposed paddle-wheel CT display method are necessary to quantitate their
      relative clinical effectiveness in the evaluation of the pulmonary vasculature,
      airways, and lungs.

PMID- 12797610
TI  - Tracheobronchomalacia: evolving role of dynamic multislice helical CT.
AB  - Paired inspiratory and dynamic expiratory multislice CT imaging is a promising
      method for diagnosing TBM. A low-dose technique should be considered for the
      dynamic portion to reduce radiation exposure. Visual and quantitative analysis of
      the central airways provide a comprehensive assessment by allowing for the
      accurate diagnosis of TBM, determining its extent, assessing for predisposing
      conditions, and aiding selection of candidates for stent placement or
      tracheoplasty procedures. This technique can also be helpful for assessing
      response of airway dynamics following therapeutic intervention.

PMID- 12797611
TI  - Pediatric multidetector body CT.
AB  - The MDCT has advantages that are uniquely suited to imaging of infants and
      children. This is one reason why the use of CT has continued to increase. There
      is also, however, an increased complexity with this technology. Because diagnosis
      is dependent on adequate quality, and inappropriately high radiation doses can
      result from poor technique, it is necessary for the radiologist to be familiar
      with the techniques of MDCT in children. With attention to these techniques, and
      appropriate application of MDCT, it is possible to maximize the yield while
      minimizing the risk to children.

PMID- 12797612
TI  - Chronic response of the rat sciatic nerve to the flat interface nerve electrode.
AB  - The chronic effects of a reshaping nerve electrode, the flat interface nerve
      electrode (FINE), on sciatic nerve physiology, histology, and blood-nerve barrier
      (BNB) are presented. The FINE electrode applies a small force to a nerve to
      reshape the nerve and fascicles into elongated ovals. This increases the
      interface between the nerve and electrode for selective stimulation and recording
      of peripheral nerve activity. The hypothesis of this study is that a small force
      applied noncircumferentially to a nerve can chronically reshape the nerve without
      effecting nerve physiology, histology, or the blood-nerve barrier permeability.
      Three FINE electrode designs were implanted on rat sciatic nerves to examine the
      nerve's response to small, moderate, and high reshaping forces. The chronic
      reshaping, physiology, and histology of the nerve were examined at 1, 7, and 28
      days postimplant. All FINEs significantly reshape both the nerve and the
      fascicles compared to controls. FINEs that applied high forces caused a
      neurapraxia type injury characterized by changes in the animal's footprint, nerve
      histology, and the BNB permeability. The physiological changes were greatest at 7
      days and fully recover to normal by 14 days postimplant. The moderate force FINE
      did not result in changes in the footprint or BNB permeability. Only a minor
      decrease in axon density without accompanying evidence of axon demyelination or
      regeneration was observe for the moderate force. The small force FINE does not
      cause any change in nerve physiology, histology, or BNB permeability compared to
      the sham treatment. An electrode that applies a small force that results in an
      estimated intrafascicular pressure of less than 30 mm Hg can reshape the nerve
      without significant changes in the nerve physiology or histology. These results
      support the conclusion that a small force chronically applied to the nerve
      reshapes the nerve without injury.

PMID- 12797613
TI  - Subfascicle stimulation selectivity with the flat interface nerve electrode.
AB  - The flat interface nerve electrode (FINE) is an alternative to cylindrical nerve
      cuffs for functional electrical stimulation (FES). By elongating the nerve in
      cross section, the FINE places more stimulating contacts around the nerve, and
      moves central axons closer to the electrode surface. Previous experiments have
      demonstrated that the FINE can activate selectively each fascicle in the cat
      sciatic nerve, and modeling studies have indicated that it should be possible to
      selectively activate groups of axons within individual fascicles. This hypothesis
      is tested using a combination of experimental and modeling techniques. Pairs of
      contacts stimulating the same fascicle were tested for subfascicle level
      selectivity, defined as the fraction of fibers activated by one contact but not
      by the other. It was possible to achieve greater than 90% selectivity with the
      FINE, but there was considerable variation in the results. The modeling studies
      showed that the selectivity achievable with a given contact pair depended
      strongly on the relative locations of the electrode and fascicle. Therefore,
      reshaping the cross section of a nerve can provide selectivity at the
      subfascicular level, but the electrode design must be optimized to improve
      selectivity across different nerve geometries.

PMID- 12797614
TI  - Wavelet entropy for subband segmentation of EEG during injury and recovery.
AB  - In this paper, subband wavelet entropy (SWE) is used for the segmentation of
      electroencephalographic signals (EEG) recorded during injury and recovery
      following global cerebral ischemia. Wavelet analysis is used to decompose the EEG
      into standard clinical subbands followed by computation of the Shannon entropy.
      The EEG was measured from rodent brains in a controlled experimental brain injury
      model by hypoxic-ischemic cardiac arrest. Results show that while the relative
      EEG power failed to reveal the order of bursting activity associated with
      recovery, SWE was used to segment the EEG and delineate the initial bursting
      periods in each subband. Based on entropy variations obtained from a cohort of
      animals with graded levels of hypoxic-ischemic cardiac arrest, an intermittent
      pattern of bursting was observed in the high frequency bands.

PMID- 12797615
TI  - Effect of blood flow on thermal equilibration and venous rewarming.
AB  - In this study we have explored the feasibility of using an isolated rat limb as
      an animal model for studying countercurrent arterial thermal equilibration and
      venous rewarming in muscle tissue. Unlike in vivo experiments in which animal
      models have been used for studying thermoregulation or temperature response in
      tissue under various physiological conditions, isolated organ or tissue provides
      for better control and more accurate measurement of the blood perfusion rate. It
      has been shown that the induced perfusion rate in the rat limb can vary from 3
      ml/(min x 100 g) at normal physiological conditions to 25 ml/(min x 100 g) during
      hyperemic conditions. Temperature distributions along the countercurrent arteries
      and veins have been measured using fine thermocouple wires. We observed a 25%-78%
      thermal equilibration along the femoral artery and its branches in intermediate
      size vessels between 700 and 300 microm diameter. This equilibration depends
      strongly on the local perfusion rate. In comparison, local perfusion rate plays a
      minor role in determining the overall venous rewarming in the rat hind limb.
      Approximately 70%-80% of the heat leaving the artery is recaptured by the
      countercurrent vein. This agrees well with our previous theoretical and
      experimental results, which show a dramatic shift in thermal equilibration
      between the supply artery and vein tissue cylinder and the secondary vessel
      tissue cylinder as the flow rate changes.

PMID- 12797616
TI  - Expandable bioresorbable endovascular stent. I. Fabrication and properties.
AB  - A bioresorbable, expandable poly(L-lactic acid) stent has been designed, based on
      a linear, continuous coil array principle, by which multiple furled lobes convert
      to a single lobe upon balloon expansion, without heating. Stent strength and
      compliance are sufficient to permit deployment by a conventional balloon
      angioplasty catheter. Several multiple lobe configurations were investigated,
      with expansion ratios ranging from 1.4 to 1.9 and expanded diameters ranging from
      2.3 to 4.7 mm. Compression resistance of the expanded stent is dependent on fiber
      coil density and fiber ply. A range sufficient for endovascular service was
      obtained, with less than 4% elastic recoil in six day saline incubation studies.
      Surface plasma treatment with di(ethylene glycol) vinyl ether significantly
      reduced platelet adhesion in a 1 h porcine arteriovenous shunt model. Patency was
      maintained in one week implant studies in the porcine common femoral artery.
      However, a strong inflammatory response, and significant reduction of the
      vascular lumen were observed following two weeks implantation. The design
      principles and fabrication techniques for this bioresorbable stent are
      sufficiently versatile that a broad range of applications can be addressed. Much
      work remains to be done, including long-term evaluation of the inflammatory
      response, and of polymer degradation. The results of this study demonstrate the
      feasibility of expandable biodegradable stent design and deployment by
      conventional means.

PMID- 12797617
TI  - Correlation between negative near-wall shear stress in human aorta and various
      stages of congestive heart failure.
AB  - The critical effect of advanced congestive heart failure is reduced blood flow in
      descending aorta resulting from mild to severe reduction in cardiac output,
      usually accompanying low ejection fraction. In these patients the heart tries to
      compensate by beating faster, but reduced blood flow combined with increased
      heart rate can lead to retrograde flow and negative shear stress along the vessel
      walls during each cardiac cycle. Our studies show that near-wall negative shear
      stress can result from an entire-retrograde flow at normal heart rates or a
      Womersley-type phase delayed near-wall retrograde flow at high heart rate and low
      ejection fraction conditions. In our experiments, a compliant aortic loop with
      appropriate pressure and flow instrumentation was used, running on either various
      aqueous glycerin solutions or property filtered, anticoagulated diluted bovine
      blood. The flow field was mapped using a General Electric Vingmed System 5
      platform. The resulting images were analyzed with Caltech's digital ultrasound
      speckle image velocimetry technique. We showed the occurrence of near-wall
      retrograde flow under certain aortic flow rates and frequencies, charted via an
      empirical relationship between Reynolds and Womersley numbers. Also, we
      demonstrated a strong correlation between retrograde flow level and transition
      from preliminary to advanced congestive heart failure patients.

PMID- 12797618
TI  - The stress-strain behavior of coronary stent struts is size dependent.
AB  - Coronary stents are used to re-establish the vascular lumen and flow conditions
      within the coronary arteries; the typical thickness of a stent strut is 100
      microm, and average grain sizes of approximately 25 microm exist in stainless
      steel stents. The purpose of this study is to investigate the effect of strut
      size on the stress strain behavior of 316 L stainless steel. Other materials have
      shown a size dependence at the micron size scale; however, at present there are
      no studies that show a material property size dependence in coronary stents.
      Electropolished stainless steel stent struts within the size range of 60-500
      microm were tensile tested. The results showed that within the size range of
      coronary stent struts a size dependent stress-strain relationship is required to
      describe the material. Finite element models of the final phase of fracture,
      i.e., void growth models, explained partially the reason for this size effect.
      This study demonstrated that a size based stress-strain relationship must be used
      to describe the tensile behavior material of 316 L stainless steel at the size
      scale of coronary stent struts.

PMID- 12797619
TI  - Fractional derivatives embody essential features of cell rheological behavior.
AB  - Mechanical moduli of cultured airway smooth muscle cells (Fabry, B., et al. Phys.
      Rev. Lett. 87:148102, 2001) reveal that the frequency dependence of cell
      rheological behavior conforms to a weak power-law relationship over a wide range
      of frequency (10(-2)-10(3) Hz). Such a behavior cannot be accounted for by
      standard viscoelastic models characterized by a discrete number of time constants
      that have been commonly used in previous studies of cell viscoelasticity.
      Fractional calculus, by contrast, provides a natural framework for describing
      weak power-law relationships and requires no assumptions about the type of
      material, the time constant distribution or the time/frequency interval in which
      rheological observations are made. In this study, we developed a rheological
      model of the cell using methods of fractional calculus. We used a least-squares
      technique to fit the model to data previously obtained from measurements on
      airway smooth muscle cells. The fit provided an excellent correspondence to the
      data, and the estimated values of model parameters were physically plausible. The
      model leads to a novel and unexpected empirical link between dynamic viscoelastic
      behavior of the cytoskeleton and the static contractile stress that it bears.

PMID- 12797620
TI  - Biomechanical properties of esophagus during systemic treatment with epidermal
      growth factor in rats.
AB  - The epidermal growth factor (EGF) is a growth factor with effects on many cell
      types and tissue. Morphometric and passive biomechanical properties were studied
      in isolated segments of the esophagus in 22 EGF-treated rats and 12 control rats.
      The rats were divided into groups with EGF treatment for 2, 4, 7, and 14 days
      (n=6 for each group except n=4 for the 14 days EGF-treatment group) or saline
      treatment (n=3 for each group). The mechanical test was performed as a distension
      experiment in vitro where the whole esophagus was stretched to its in situ length
      and distended with pressures up to 10 cm H2O using a ramp distension protocol.
      The pressure and outer diameter were recorded. Circumferential stress (force per
      area) and strain (deformation) were computed from the diameter and pressure data
      using the zero-stress state as reference. The zero-stress state was obtained by
      cutting esophageal rings radially. This caused the rings to open up into a
      sector. EGF induced pronounced morphometric changes, e.g., the wall thickness,
      wall cross-sectional area, and inner and outer circumferential lengths
      significantly increased during the EGF treatment. Histological analysis showed
      mucosa and submucosa growth during EGF treatment. The opening angle and residual
      strains increased with the highest value in the 14 days EGF-treated group
      (P<0.05). The change in opening angle depended largely on the change in mucosa
      thickness. Furthermore, the circumferential stiffness of the esophagus reached a
      maximum after 7 days EGF treatment (P<0.01).

PMID- 12797621
TI  - Effects of creep and cyclic loading on the mechanical properties and failure of
      human Achilles tendons.
AB  - The Achilles tendon is one of the most frequently injured tendons in humans, and
      yet the mechanisms underlying its injury are not well understood. This study
      examines the ex vivo mechanical behavior of excised human Achilles tendons to
      elucidate the relationships between mechanical loading and Achilles tendon
      injury. Eighteen tendons underwent creep testing at constant stresses from 35 to
      75 MPa. Another 25 tendons underwent sinusoidal cyclic loading at 1 Hz between a
      minimum stress of 10 MPa and maximum stresses of 30-80 MPa. For the creep
      specimens, there was no significant relationship between applied stress and time
      to failure, but time to failure decreased exponentially with increasing initial
      strain (strain when target stress is first reached) and decreasing failure
      strain. For the cyclically loaded specimens, secant modulus decreased and cyclic
      energy dissipation increased over time. Time and cycles to failure decreased
      exponentially with increasing applied stress, increasing initial strain (peak
      strain from first loading cycle), and decreasing failure strain. For both creep
      and cyclic loading, initial strain was the best predictor of time or cycles to
      failure, supporting the hypothesis that strain is the primary mechanical
      parameter governing tendon damage accumulation and injury. The cyclically loaded
      specimens failed faster than would be expected if only time-dependent damage
      occurred, suggesting that repetitive loading also contributes to Achilles tendon
      injuries.

PMID- 12797622
TI  - Development of a three-dimensional finite element model for carpal load
      transmission in a static neutral posture.
AB  - A three-dimensional developmental finite element model has been created to
      analyze load transmission pathways in the constrained carpus during static
      compressive loading. The bone geometry was extracted from an in vivo computed
      tomography scan using a combination of commercial and proprietary software. The
      complete geometry, including bone, cartilage, and ligament tissues, was compiled
      using a commercial finite element program. This model extends the state of
      biomechanical modeling by being the first to incorporate all eight carpal bones
      of the wrist and the related soft tissues in three dimensions. The model results
      indicate that cartilage material modulus and unconstrained carpal rotation have
      substantial impacts on the articular contact patterns and pressures.

PMID- 12797623
TI  - Trabecular shear stresses predict in vivo linear microcrack density but not
      diffuse damage in human vertebral cancellous bone.
AB  - Linear microcracks and diffuse damage (staining over a broad region) are two
      types of microscopic damage known to occur in vivo in human vertebral trabecular
      bone. These damage types might be associated with vertebral failure. Using
      microcomputed tomography and finite element analysis for specimens of cancellous
      bone, we estimated the stresses in the trabeculae of human vertebral tissue for
      inferosuperior loading. Microdamage was quantified histologically. The density of
      in vivo linear microcracks was, but the diffuse damage area was not, related to
      the estimates of von Mises stress distribution in the tissue. In vivo linear
      microcrack density increased with increasing coefficient of variation of the
      trabecular von Mises stress and with increasing average trabecular von Mises
      stress generated per superoinferior apparent axial stress. Nonlinear increase in
      linear crack density, similar to the increase of the coefficient of variation of
      trabecular shear stresses, with decreasing bone stiffness and bone volume
      fraction suggests that damage may accumulate rather rapidly in diseases
      associated with low bone density due to the dramatic increase of shear stresses
      in the tissue.

PMID- 12797624
TI  - Effects of a fixation screw on trabecular structural changes in a vertebral body
      predicted by remodeling simulation.
AB  - Computational simulation of trabecular surface remodeling was conducted to
      investigate the effects of a spinal fixation screw on trabecular structural
      changes in a vertebral body. By using voxel-based finite elements, computational
      models of the bone and screw were constructed in two structural scales of a
      vertebral body with an implanted screw and a bone-screw interface. In the
      vertebral body, the implantation of the fixation screw caused changes in the
      mechanical environment in cancellous bone, leading to trabecular structural
      changes at the cancellous level. The effects of the screw on trabecular
      orientation were greater in the regions above and below the screw than in those
      in front of the screw. In the case of the bone-screw interface, trabecular
      structural changes depended on the direction of load applied to the screw. It was
      suggested that the bone resorption predicted in the pull-out loading case is a
      candidate cause of the loosening of the screw. The results indicate that the
      effects of the implanted screw on trabecular structural changes are more
      important for longer-term fixation.

PMID- 12797625
TI  - Using the fast orthogonal search with first term reselection to find subharmonic
      terms in spectral analysis.
AB  - The fast orthogonal search (FOS) algorithm has been shown to accurately model
      various types of time series by implicitly creating a specialized orthogonal
      basis set to fit the desired time series. When the data contain periodic
      components, FOS can find frequencies with a resolution greater than the discrete
      Fourier transform (DFT) algorithm. Frequencies with less than one period in the
      record length, called subharmonic frequencies, and frequencies between the bins
      of a DFT, can be resolved. This paper considers the resolution of subharmonic
      frequencies using the FOS algorithm. A new criterion for determining the number
      of non-noise terms in the model is introduced. This new criterion does not assume
      the first model term fitted is a dc component as did the previous stopping
      criterion. An iterative FOS algorithm called FOS first-term reselection (FOS
      FTR), is introduced. FOS-FTR reduces the mean-square error of the sinusoidal
      model and selects the subharmonic frequencies more accurately than does the
      unmodified FOS algorithm.

PMID- 12797626
TI  - Contrasting messages but not contradicting results from ALLHAT and ANBP2.

PMID- 12797627
TI  - Angiotensin AT1/AT2 receptors: regulation, signalling and function.
AB  - Angiotensin II (Ang II), the biologically active component of renin-angiotensin
      system (RAS), acts through two receptor subtypes, the AT1 and the AT2 receptor.
      All classic physiological effects of Ang II, such as vasoconstriction,
      aldosterone and vasopressin release, sodium and water retention and sympathetic
      facilitation, are mediated by the AT1 receptor. Ang II, via its AT1 receptor, is
      also involved in cell proliferation, left ventricular hypertrophy,
      nephrosclerosis, vascular media hypertrophy, endothelial dysfunction, neointima
      formation and processes leading to athero-thrombosis. Recent investigations have
      established a role for the AT2 receptor in cardiovascular, brain and renal
      function as well as in the modulation of various biological processes involved in
      development, cell differentiation, tissue repair and apoptosis. This review
      summarizes new insights in the regulation, signalling and (patho-) physiological
      functions of AT1 and AT2 receptors. An extensive review on angiotensin receptors
      has been published recently (de Gasparo M et al., Pharmacol Rev 2000; 52: 415
      72).

PMID- 12797629
TI  - Associations between arterial compliance and anthropometry of children from four
      ethnic groups in south africa: the THUSA BANA Study.
AB  - AIM: To investigate whether associations and differences exist regarding the
      arterial compliance, dietary intake and anthropometric parameters of children of
      four different ethnic groups in South Africa. STUDY DESIGN: In this study, 1244
      children from four ethnic groups, aged 10-15 years, were randomly selected from
      five regions of the North West Province. Blood pressure was measured with a
      Finapres apparatus and analysed to obtain systemic arterial compliance.
      Measurements were done to obtain body mass index (BMI), waist-to-hip ratio and
      percentage body fat. Dietary intake was determined with a 24-h dietary recall
      questionnaire. RESULTS: The black and mixed-origin subjects indicated the lowest
      values (p < or = 0.05) for BMI, percentage body fat, and dietary intake, whereas
      the white and Indian subjects showed significantly higher values than the other
      ethnic groups. The white and Indian children had significantly higher arterial
      compliance than the black and mixed-origin children at all ages from 10 to 15
      years. Compliance showed significant correlations with all anthropometric
      parameters. CONCLUSION: Since black and mixed-origin children have the highest
      prevalence of undernutrition and stunted growth, it is suggested that parental
      undernutrition and inadequate nutrition in early life, associated with lower
      arterial compliance, may lead to the onset of adult hypertension.

PMID- 12797628
TI  - Cardiac damage in hypertensive patients with inverse white coat hypertension.
      Hospitalet study.
AB  - BACKGROUND: Few studies have assessed the relationship between ambulatory blood
      pressure (BP) and cardiac damage in essential hypertensive patients with inverse
      white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in
      untreated grade 1-2 hypertension and to assess possible differences in cardiac
      damage among patients with IWCH, white coat hypertension (WCH) and the rest of
      patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and
      eleven patients with grade 1-2 hypertension were sequentially included. A good
      quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/-
      12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP
      higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was
      defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained
      in 174 patients. We considered left ventricular hypertrophy a left ventricular
      mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%),
      and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate
      position between WCH and the rest of grade 1-2 hypertension patients. The IWCH
      patients showed 24-h, daytime and night-time BP higher than the other groups.
      Left ventricular mass was significantly greater in patients with IWCH than in the
      other grade 1-2 hypertension patients after adjusting for age, gender, body mass
      index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91).
      CONCLUSION: IWCH is independently associated with higher values of left
      ventricular mass in patients with grade 1-2 hypertension.

PMID- 12797630
TI  - Serum uric acid and hemorheology in borderline hypertensives and in subjects with
      established hypertension and left ventricular hypertrophy.
AB  - Serum uric acid (SUA) but also hemorheological parameters such as hematocrit
      (Hct) and whole blood viscosity (WBV) are markers of cardiovascular risk.
      Increased blood cell volume is one of the known causes of hyperuricemia. We
      therefore aimed to investigate the relationship between SUA and hemorheology in
      untreated borderline hypertensive young men (n = 67) and in subjects with
      established hypertension and left ventricular hypertrophy (n = 40) examined when
      they had been without treatment for 2 weeks. We found positive correlations
      between SUA and Hct (r = 0.46, p < 0.0001), hemoglobin (Hgb) (r = 0.40, p =
      0.001), mean blood pressure (BP) (r = 0.39, p = 0.001) and body weight (r = 0.26,
      p = 0.036) in the borderline hypertensive young men. No relation between SUA and
      glucose disposal rate (GDR) assessed with hyperinsulinemic isoglycemic glucose
      clamp appeared (r = -0.06, p = 0.633). Multiple regression analysis showed that
      33% of the variation in SUA could be explained by BP and Hct. We also found
      positive correlations between SUA and Hgb (r = 0.40, p = 0.011) and body weight
      (r = 0.42, p = 0.006) and an inverse trend with GDR (r = -0.27, p = 0.087) in the
      subjects with established hypertension. Multiple regression showed that 32% of
      the variation in SUA was explained by Hgb and body weight. These data suggest
      that hemorheology may be involved in the uric acid metabolism in borderline as
      well as in established hypertensives. Hemorheology may possibly be a link between
      SUA and cardiovascular risk. There was no relation between SUA and insulin
      resistance in these hypertensive groups.

PMID- 12797631
TI  - Blood pressure and contributing factors in inhabitants of Estonia: 15-year
      trends.
AB  - AIM: To study the 15-year trends of blood pressure (BP) values in inhabitants of
      Estonia, three independent random samples of the population of Tallinn aged 20-54
      years were examined in 1984/86, 1992/94 and in 1999/2001. RESULTS: A substantial
      decrease in BP values was observed in the population of Tallinn by the early
      1990s; it continued to a smaller extent during the late 1990s. An improvement in
      some factors contributing to the development of arterial hypertension: decrease
      in body mass index (BMI) mean values and positive dietary changes were observed
      during this period. In the late 1990s, the changes in contributing factors were
      less synonymous. In men, the BMI mean values, intake of calories and alcohol
      increased but smoking rates dropped substantially; physical activity and P/S
      ratio increased. In women, the BMI mean values, which decreased considerably
      between the 1980s and early 1990s, remained stable, as well as smoking rates;
      physical activity increased and positive changes in nutrition were more
      pronounced than in men. The BP values also decreased in women to a greater extent
      than in men. CONCLUSION: Favourable trends in BP and contributing factors were
      found in Estonia during the transition period accompanied by a cardiovascular
      disease mortality decline since 1995.

PMID- 12797632
TI  - Calcium urolithiasis, blood pressure and salt intake.
AB  - OBJECTIVES: To determine whether stone-formers have higher BP than controls drawn
      from the general population and matched for age, sex and ethnic origin and to
      compare the relationship between sodium and calcium excretion in the two groups.
      PATIENTS AND METHODS: Thirty-six patients [mean (+/-standard deviation, SD) =
      49.0 +/- 11.7 years; range 27-70 years] with kidney or ureteric stones and 108
      controls (mean age of 49.6 +/- 6.8 years; range 39-61 years), matched for gender,
      ethnic origin and age group were studied. Patients and controls underwent
      physical measurements, a venous blood sample and they were asked to collect a 24
      h urine sample for sodium, potassium, calcium and creatinine. RESULTS: Stone
      formers were significantly heavier and had higher BP than age-, sex- and ethnic
      matched population controls. Whilst the difference in systolic BP was independent
      of the difference in body mass index [16.8 mmHg (7.2-26.4 mmHg), p = 0.001), the
      difference in diastolic BP was attenuated after adjustment for body mass [1.8 (
      3.4 to 7.1), p = 0.49]. Stone-formers passed less urine than controls [-438
      ml/day (95% CI -852 to -25), p = 0.038]. They had higher urinary calcium than
      controls [+3.7 mmol/day (2.8-4.6 mmol/day), p < 0.001], even when expressed as
      ratio to creatinine [+0.20 (0.11-0.29), p < 0.001]. Sodium excretion was
      positively associated with urinary calcium in both stone-formers and in controls.
      The slopes were comparable (0.92 vs 0.98 mmol Ca/100 mmol Na) so that for any
      level of sodium excretion (or salt intake), stone-formers had a higher calcium
      excretion than controls. CONCLUSIONS: In stone-formers, the BP is higher than in
      controls. Stone-formers excrete more calcium than controls do. In stone-formers
      and controls, the relationship between urinary sodium and calcium is similar.
      Since this relationship results from an effect of sodium on calcium, a reduction
      in salt intake may be a useful method of reducing urinary calcium excretion in
      stone-formers. However, the "relative" hypercalciuria seen in stone-formers is
      independent of salt intake and may well reflect an underlying genetic
      predisposition.

PMID- 12797633
TI  - The saga of bronchial asthma.

PMID- 12797634
TI  - Prevalence of bronchial asthma among bank employees of Vellore using
      questionnaire-based data.
AB  - Asthma and related allergic disorders are reported to be rare in poor and
      developing countries and their prevalence is expected to rise with urbanisation.
      Investigation was carried to see the prevalence of asthma and asthma-related
      symptoms by using a simple questionnaire-based data collection. One hundred and
      twenty bank employees were studied in the age group 25-55 years in 4 centres of
      Vellore town. A one-page questionnaire in English regarding asthma and allergic
      symptoms was used to assess the prevalence and the details of medical care
      utilisation by those who were asthmatics. The prevalence of self-reported
      bronchial asthma was 8.3% and that of asthma-related symptoms 15.8%. A
      significant number of subjects with symptoms suggestive of asthma self-reported
      themselves as non-asthmatic. There was a significant association between those
      who had symptoms of asthma and a positive family history of asthma. Most of the
      asthmatic subjects using allopathic medicines reported a poor quality of life,
      despite treatment. The prevalence of asthma in Vellore town is more than that
      reported in other studies carried out at different centres in India. The
      prevalence may actually be higher since a significant number of subjects with
      symptoms suggestive of asthma reported themselves as non-asthmatic subjects. As
      expected, positive family history was forthcoming in subjects with asthma
      symptoms. Most asthmatic subjects have not experienced a significant improvement
      in their quality of life, which could indicate sub-optimal management. These
      findings can form the basis for further studies to investigate factors that lead
      to these variations.

PMID- 12797635
TI  - Foetal heart rate patterns in early labour in low and high risk pregnancies and
      its correlation with perinatal outcome.
AB  - The present prospective study included 173 randomly selected primigravidae at
      admission in early labour. Of these, 88 cases were of low risk and 85 cases were
      of high risk, on the basis of antenatal risk factors. All the cases were
      subjected to a twenty minutes recording of the foetal heart rate patterns and
      uterine contractions in early labour. It was interesting to note that, 13% of so
      called low risk pregnancies showed abnormal foetal heart pattern and thus became
      high risk in labour. No statistically significant difference was seen in the
      baseline heart rate and variability patterns in low and high risk pregnancies.
      However, all types of decelerations were more frequent in the high risk
      pregnancies. It was observed that as compared to baseline heart rate and
      variability, decelerations were better predictors of a poor perinatal outcome
      especially late decelerations and variable decelerations with ominous features,
      the mean Apgar scores at one minute of the two being 5.6 and 6.8 respectively.

PMID- 12797636
TI  - Role of non-H2O2 producing lactobacilli and anaerobes in normal and complicated
      pregnancy.
AB  - Lactobacilli (Doederlein's bacilli) are the most important predominant protective
      agents of the vaginal microbial ecosystem and alteration in vaginal pH directly
      speculates the concentration of lactobacilli. Currently, recognition of anaerobic
      lactobacilli (non-H2O2 producing lactobacilli) had further raised its
      significance. Therefore, the present study was aimed to explore the role of non
      H2O2 lactobacilli and its association with other anaerobes in 100 cases of
      complicated pregnancy, 75 cases of normal pregnancy and 35 cases in non-pregnant
      women. Vaginal and cervical swabs were obtained and were inoculated in special
      and suitable media. Anaerobic lactobacilli (non-H2O2 producing) were more common
      genital microbes in women of complicated pregnancy (56.0%) than in normal
      pregnancy (34.7%) and in control group (14.2%). Rate of recovery of non-H2O2
      producing lactobacilli increased when pathogenic bacteria especially anaerobes
      dominate the genital microflora. Anaerobic lactobacilli were seen in higher
      numbers when they were associated with bacteroides sp and other anaerobes. They
      were significantly reduced when aerobes predominated in flora; the correlation
      have been discussed.

PMID- 12797637
TI  - Antibiotic sensitivity and resistance profile of the micro-organisms responsible
      for urinary tract infection observed in Kashmir, India.
AB  - Urinary tract infection happens to be common and is generally treated empirically
      by general practitioners, for which they need to be aware of the locally
      prevalent strains and their sensitivity pattern. Since over the last few decades
      the resistance pattern of urinary isolates has been showing dramatic changes all
      over the world, it was felt useful to study the existing microbiological pattern
      of the urinary tract infections in Kashmir valley and to assess the sensitivity
      profile of the isolated organisms to the generally used antibiotics for empirical
      therapy in primary health care settings. The retrospective analysis of 324 such
      samples which were found positive for pathological bacteria by the microbiology
      laboratory of Government Medical College, Srinagar, Kashmir revealed that 90.12%
      of the isolates were E. coli followed by klebsiella (7.72%) and staphylococcus
      (1.24%). Significantly 43.57% of the E. coli exhibited resistance to the commonly
      used antibiotics, and the most effective in-vitro agents were found to be
      amikacin followed by gentamicin among the injectables and ciprofloxacin among the
      orally administered ones. Other useful oral antibiotics were nitrofurantoin,
      chloramphenicol and nalidixic acid. The organisms showed resistance to currently
      preferred urinary antibiotics and chemotherapeutic agents like co-trimoxazole,
      norfloxacin, pefloxacin and cephalexin. Conclusion was that among the orally
      administered antibiotics ciprofloxacin remains the choice while other quinolones
      or derivatives have turned ineffective and among the injectables gentamicin is
      still effective.

PMID- 12797638
TI  - Age of treatment of undescended testis--a study.
AB  - A retrospective study was conducted for a period of 4 years during 1992-1995 at
      Medical College Hospital, Alappuzha, Kerala to find out whether boys with
      undescended testis got treated at ideal age. Discharge summaries of boys who were
      treated for undescended testis in this hospital were studied. There were 139
      patients with 162 undescended testes. Mean age of operation was 5 years (range-
      11 months to 12 years). There were 19.4% patients who were less than 2 years of
      age. It was found out that 11.1% of total testes were atrophic/vanished.
      Orchiopexy was done in almost all remaining cases. Majority of boys with
      undescended testis attended for treatment at a higher age than that recommended.
      The ideal age of treatment at present and its scientific basis are highlighted.

PMID- 12797639
TI  - Contact lens wear and microbial keratitis.
AB  - Common types of contact lens are hard, rigid gas-permeable or soft lenses. Most
      lenses are worn on a daily basis. Cosmetic lenses are worn for non-medical
      indications. Microbial keratitis, a rare but most significant complication is
      discussed in this article. Pseudomonas aeruginosa and staphylococci are the most
      common organisms cause infective keratitis. Fungi and acanthamoeba are also
      responsible. The causes of increased susceptibility to infection are poor lens
      hygiene, adhesion of bacteria to lens surface and hypoxia. Preventing measures to
      be taken while wearing contact lens are discussed in a nutshell. Ocular pain,
      conjunctival infection, photophobia, epiphora and reduced vision are some of the
      symptoms of corneal infection. Diagnostic laboratory investigations are to be
      carried out immediately when a microbial corneal ulcer is suspected. Acanthamoeba
      can be cultured from corneal scrapes. Immunologically based fluorescein labelling
      techniques appear to be more sensitive than simple staining. The treatment
      consists of medical and surgical intervention. Corneal thinning, descemetocele
      formation and perforation are possible complications.

PMID- 12797640
TI  - Familial hypercholesterolaemia--a case report.
AB  - A case report of a 9-year-old female presenting with cutaneous xanthoma and other
      findings suggestive of homozygous familial hypercholesterolaemia along with
      abnormalities in serum lipid profile in other siblings is presented in view of
      its rarity.

PMID- 12797641
TI  - Gradenigo's syndrome--a rare complication of otitis media.
AB  - Petrous apicitis is a rare intracranial complication of otitis media. A 4-year
      old female child was presented with persistent ear discharge, retro-orbital pain
      and lateral rectus palsy (triad of Gradenigo's syndrome). A right temporal burr
      hole was placed and tapping was done under antibiotic coverage. Turbid
      cerebrospinal fluid could be drained. Follow-up could not be done as the patient
      refused treatment and was discharged against medical advice.

PMID- 12797643
TI  - Small family norms.

PMID- 12797642
TI  - Intravaginal foreign body--a rare cause of large bowel obstruction.
AB  - Intravaginal foreign body rarely causes bowel obstruction. A 60-year-old female
      presented with pain in lower abdomen. On examination, her abdomen was found
      distended with muscle guard. Per rectal examination revealed a hard mass 3-4 cm
      away from the anal verge. There was leucocytosis and straight x-ray showed
      features of large bowel obstruction. Exploratory laparatomy was performed. The
      large bowel was distended with a hard mass felt in the pelvis. On manipulation
      the mass of about 15 cm x 12 cm x 12 cm size came out of the vagina and it
      happended to be a brick. The recovery was uneventful.

PMID- 12797644
TI  - Good decision.

PMID- 12797645
TI  - Cause of dietary deficiency of calcium.

PMID- 12797646
TI  - Hepatic tuberculosis--a case report.

PMID- 12797648
TI  - A moment in the spotlight.

PMID- 12797647
TI  - Evaluation of efficacy, safety and tolerability of valdecoxib in osteo-arthritis
      patients--an Indian study.
AB  - Valdecoxib, a COX-2 inhibitor, has been introduced as a new treatment for osteo
      arthritis (OA). The present study was conducted to evaluate the efficacy, safety
      and tolerability of valdecoxib, in OA patients in an Indian setting. The present
      4-week study was a prospective, non-comparative, assessor blind, single group,
      multicentric trial with OA patients treated with valdecoxib, 10 mg once a day.
      Efficacy was assessed by analysing the changes in Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), patient's
      and physician's global assessment of arthritis. The incidence of adverse events
      was monitored throughout the study. There was a clinical and statistical
      significant improvement in the mean pain score, stiffness score, physical
      function, composite WOMAC index score and VAS (p<0.05). Patient's and physician's
      global evaluation of valdecoxib treatment was very good to good in 84.1% and
      83.6% of cases respectively. The present study has shown that valdecoxib, in a
      dose of 10 mg/day given over 4 weeks, is an effective and safe treatment for the
      signs and symptoms of OA of hip and knee joints.

PMID- 12797649
TI  - Understanding uncertainty.

PMID- 12797651
TI  - Cyber chief.

PMID- 12797650
TI  - Another peril.

PMID- 12797652
TI  - Merely lights and wires?

PMID- 12797653
TI  - Getting journalists up to speed.

PMID- 12797654
TI  - Opening address from the first statewide medical press conference in 1949
      [classical article].

PMID- 12797655
TI  - When medicine makes the news.

PMID- 12797656
TI  - Subject and source trends in the Star Tribune's coverage of the medical
      literature.
AB  - Medical developments are front-page news, and many health-related news reports
      are based on articles from the medical research literature. We analyzed the
      subjects and sources of literature-based medical news articles that appeared in
      Minnesota's largest newspaper, the Star Tribune, from May 1994 through December
      2002. Data were collected by searching Health and Medicine in the News
      (http://www.biomed.lib.umn.edu/hmed), an online database that catalogues Star
      Tribune articles on health and medical topics. The most common topics of the
      3,419 literature-based medical news articles appearing during the period were
      cancer, obesity/diet/exercise, and heart disease. The New England Journal of
      Medicine was the source cited most often, followed by the Journal of the American
      Medical Association, Science, and Nature. We compared the most common subjects
      covered in the news articles with those covered in MEDLINE and with the most
      common causes of death in the United States. Diet, smoking, AIDS, and Alzheimer's
      disease are represented much more often in the Star Tribune than in the medical
      literature in general, and articles on genetics and pregnancy were found much
      more often in the medical literature than in this sample of newspaper articles.
      Cancer and heart disease, which were the first and third most-often-covered
      topics in the Star Tribune, are 2 of the 3 top causes of death in this country.

PMID- 12797657
TI  - New treatments for age-related macular degeneration.
AB  - The estimated increase in life expectancy of the U.S. population will result in a
      greater incidence of age-related macular degeneration (AMD) in the next few
      decades. Exudative AMD, which is characterized by choroidal neovascularization,
      carries a high risk of severe central vision loss and can compromise an
      individual's independence and quality of life. The increasing burden of AMD has
      created an acute need for more effective treatments. Results from a recent large
      scale study have shown that supplementation with antioxidants and zinc reduces
      the risk of progression of dry to exudative AMD. Standard thermal laser
      photocoagulation can reduce the risk of central vision loss in exudative AMD in a
      limited number of patients. The recent advent of photodynamic laser therapy has
      increased the number of patients with exudative AMD who can benefit from
      treatment. This paper summarizes the clinical presentation of AMD and reviews
      treatments that are currently available, as well as treatments in development.

PMID- 12797659
TI  - When you're the source.

PMID- 12797658
TI  - Rectal impalement: a case review.
AB  - Pediatric impalement injuries to the rectum are rare, and delays in diagnosis can
      be life threatening. We report the case of a young girl who was accidentally
      impaled on a dive stick. A review of historical aspects of rectal trauma and
      current management techniques are discussed. Rectal injuries in the pediatric
      population most often result from accidental impalement, sexual abuse, or blunt
      trauma. In contrast, most rectal injuries in adults are caused by missile wounds.
      Moreover, because rectal injury is fairly uncommon in children, physicians
      evaluating patients may miss signs of serious injury. Signs of external trauma
      may be minimal when rectal perforation exists, so delays in diagnosis are not
      uncommon.

PMID- 12797660
TI  - State budget, prose or con?

PMID- 12797661
TI  - Lawmakers debate health care legislation.

PMID- 12797662
TI  - Oracles, plagues, and sound bites.

PMID- 12797663
TI  - Mini-forum on multiple sclerosis (MS) and hyperbaric oxygen therapy.

PMID- 12797664
TI  - Hyperbaric oxygen therapy and multiple sclerosis.

PMID- 12797665
TI  - Diver with acute abdominal pain, right leg paresthesias and weakness: a case
      report.
AB  - A 29-year-old man was brought to an emergency department by the United States
      Coast Guard with chief complaints of severe abdominal pain, right leg paresthesia
      and weakness following four deep air dives. Physical examination before
      recompression treatment was remarkable for diffuse abdominal tenderness and right
      leg weakness. The patient was diagnosed in the emergency room with type II
      decompression sickness (DCS) and underwent standard recompression therapy. He
      experienced complete resolution of weakness after hyperbaric oxygen (HBO)
      therapy, but his abdominal pain was persistent. Further investigation led to the
      diagnosis of acute appendicitis with perforation. The patient underwent
      appendectomy and intravenous antibiotic therapy and was discharged to his home on
      hospital day five without complications. This case reinforces the importance of
      careful clinical assessment of divers and illustrates the potentially wide
      differential diagnosis of DCS. This is the first reported case of recompression
      treatment of a diver with acute appendicitis and type II DCS.

PMID- 12797667
TI  - Alternobaric oxygen therapy in long-term treatment of Meniere's disease.
AB  - Hyperbaric oxygen therapy (HBQ) has been used for several years as a treatment
      for Meniere's disease, particularly in Sweden. In this study continuous
      variations in pressure (from 1.7 to 2.2 ATA; alternobaric oxygen therapy: ABOT)
      were used to decrease endolymphatic hydrops, the typical histopathological
      substrate of Meniere's disease by increasing hydrostatic pressure and mechanical
      stimulation of the endolymphatic flow toward the duct and the endolymphatic sac,
      which produces a consequent increase in the dissolved O2 content in the labyrinth
      liquid, which should contribute to recovering cell metabolism and restoring
      cochlear electrophysiological function to normal. An experimental group of 20
      patients suffering from unilateral Meniere's disease received a total of 15 ABOT
      treatment sessions during the acute episodes. Treatment foresaw two days without
      therapy every five days of application. Maintenance treatment consisted of one
      session per day for five consecutive days every month for one year. Thereafter,
      during the second, third, and fourth years of treatment, patients were submitted
      to one session per day for five consecutive days every three months. A control
      group of 18 patients suffering from Meniere's disease was treated with 10%
      glycerol i.v. (during the acute episodes) and with betahistine (8 mg x 3/day) in
      the periods in between. Mean pure tone average (PTA in dBHL) hearing thresholds
      at octave frequencies from 500 to 3,000Hz, and frequency of episodes of vertigo
      and tinnitus, both after 15 days of treatment and at the end of a four-year
      follow-up, were compared for both groups according to the 1995 Committee on
      Hearing and Equilibrium criteria. No statistically significant differences were
      found between the two groups at the end of the first 15 days of treatment.
      However, at the end of the follow-up period, patients treated with ABOT had
      significantly fewer vertiginous episodes and improved PTAs and tinnitus compared
      to the controls. The results support the use of ABOT as a valid alternative to
      drugs in the long-term treatment of Meniere's disease.

PMID- 12797666
TI  - The incidence of venous gas emboli in recreational diving.
AB  - From 1989-91, the Divers Alert Network monitored recreational divers for Doppler
      detected venous gas emboli (VGE) and depth-time profiles following multi-day,
      repetitive, multi-level exposures. A Spencer score >0 occurred in 61 of 67
      subjects (91%) and 205 of 281 dives (73%). No subject developed decompression
      sickness (DCS) on monitored days although 102 dives (36.3%) scored at Spencer
      Grades 2 or 3 (High Bubble Grade, HBG). We recorded the depth-time profiles with
      Suunto dive computers and estimated exposure severity with a probabilistic
      decompression algorithm. The HBG incidence increased 53% over the range of
      exposure severity (p < 0.001) in the divers, was approximately 20% higher for
      repetitive dives than for first dives, and decreased approximately 25% over the 6
      8 days of multi-day diving (p < 0.001) suggesting a phenomenon similar to DCS
      adaptation. The observed HBG incidence was approximately 20% higher for males
      than females. Older male divers had a 25% increase in observed incidence of HBG
      while older female divers showed a 55% increase when compared to their younger
      counterparts.

PMID- 12797668
TI  - Levels of anxiety and hostility in South African Navy divers.
AB  - This study aimed to describe the levels of anxiety and hostility in a group of 45
      SA Navy divers, by analysing their scores on an Anxiety Scale and Hostility and
      Directed Hostility Questionnaire. Results indicate that divers experience average
      anxiety compared with the norm groups. They have a higher urge for acting out
      their hostility, and are more critical of others than the norm group. Their
      overall hostility scores are higher than that of the general population. To
      determine if this differs from other naval personnel, the diver group was
      compared to a sample of 40 general navy sailors and 20 sport divers. The navy
      divers' scores displayed a higher urge to act out than the general navy, which in
      turn scored higher than the sport divers. Both the navy divers and general navy
      groups had higher total hostility scores than the civilian divers. It is
      concluded that the results are contextually appropriate, but not meaningful for
      selection of navy divers.

PMID- 12797669
TI  - Hyperbaric oxygen improves healing in experimental rat colitis.
AB  - This study was designed to investigate therapeutic effects of hyperbaric oxygen
      on experimentally induced colitis in rats by assessing oxidative tissue damage,
      neutrophil accumulation and histological changes. Six groups of animals were
      used. No procedures were done in the sham group. In the vehicle group, 50%
      ethanol-induced colitis, and in four other groups, 2,4,6-trinitrobenzene
      sulphonic acid-induced colonic inflammation was achieved. In acute and chronic
      colitis non-treatment groups, no other procedure was done. In acute and chronic
      colitis hyperbaric oxygen treatment groups, rats underwent hyperbaric oxygen
      treatment for two or fourteen days. On the third and fifteenth days respectively
      tissue and blood samples were taken for microscopic and macroscopic damage
      assessment, myeloperoxidase activity and serum carbonyl content measurements.
      There was significant colonic tissue damage in non-treatment groups at 48 hours
      and 14 days. Hyperbaric oxygen treatment ameliorated the macroscopic damage
      significantly in chronic colitis. Amelioration of microscopic changes was not
      significant in each hyperbaric oxygen-treated group. Hyperbaric oxygen treatment
      significantly reduced tissue myeloperoxidase activity in acute colitis and
      decreased plasma carbonyl content in chronic colitis. In the present study,
      hyperbaric oxygen treatment significantly ameliorated trinitrobenzene sulphonic
      acid-induced chronic colitis in rats.

PMID- 12797670
TI  - A method of patch clamp recording in hyperbaric oxygen.
AB  - A method of patch clamp recording in hyperbaric oxygen is described which is
      derived from a method for patch clamping at high hydrostatic pressure. Excised
      patches equilibrate with hyperbaric oxygen within 10 minutes. Experiments with BK
      channels expressed in HEK 293 cells showed that 1 MPa O2 caused an increase in
      the ionic permeability of the patch, an effect accelerated in the presence of
      ferrous ions. Seal resistance was unaffected. Small negative currents, (VH - 40
      to - 65 mV, symmetrical KCl solutions), apparent in skewed all-points amplitude
      histograms, reduced the signal to noise ratio. In some patches the BK channel
      activity was inhibited and in others it persisted with the currents becoming
      irresolvable in the increased noise.

PMID- 12797671
TI  - Prescription medication use aboard US submarines during periods underway.
AB  - Since January 1997, automated medical records from U.S. submarines have been
      stored in a centralized database as part of a descriptive epidemiology study. 200
      medical encounter notes were randomly selected from 1,017 initial health visits
      during submarine underway periods between April 1996 and January 1998. Medication
      prescription appropriateness was assessed using a modified Medication
      Appropriateness Index (MAI) described in the literature. Seven diagnostic
      categories accounted for 51.4% of all diagnoses: acute upper respiratory
      infections (17.6%), superficial wounds (9.7%), elevated blood pressure without
      the diagnosis of hypertension (7.9%), sprain/strains (4.7%), skin infections
      (4.3%), eye disorders (3.6%), and ear disorders (3.6%). Prescribed medications
      were consistent with the care of minor health problems. Mean number of
      medications prescribed per encounter was 1.4 +/- 1.1 (S.D.). 84% of prescribed
      medications were assigned a modified MAI summary score of 0, indicating the
      prescription was appropriate in all aspects. However, anti-infective medication
      prescriptions demonstrated a significant proportion of non-zero summary scores
      suggesting some room for improvement in the prescribing practices for this
      specific medication category.

PMID- 12797672
TI  - Current concepts of the irritable bowel syndrome.
AB  - The irritable bowel syndrome is one of the most common clinical problems
      encountered by the generalist and gastroenterologist. The goal of this review is
      to critically evaluate, based on available peer-reviewed literature, the current
      status of our understanding of the pathophysiology of the irritable bowel
      syndrome. The epidemiology of this disorder, including the characteristics of its
      presentation, natural history and associated phenomena, have been clarified.
      Differences between those who seek specialist care ('the consulters') and those
      in the community are now recognized. While, in both, symptoms may be similar in
      nature and severity; 'the consulters' are differentiated by how they react to
      their complaints. In terms of pathophysiology, the focus has moved to visceral
      sensation and central perception and has led to the identification of visceral
      hypersensitivity, visceral hyperalgesia and abnormal central perception of
      visceral events. This is not to dismiss dysmotility; subtle abnormalities in gas
      transit may be closely associated with the induction of certain symptoms. On the
      psychological front, attention now focuses on such complex issues as
      somatosization, abuse and response to major life events. Interactions between
      enteric flora, mucosal inflammation, immune phenomena and the enteric neuro
      muscular apparatus also attract interest; the entity of post-infectious irritable
      bowel is now clearly recognized and there is experimental evidence to suggest a
      role for inflammation. While the precise aetiology of irritable bowel syndrome
      remains uncertain, considerable progress has been made, with recent advances in
      pathophysiology offering hope for the development of new therapeutic approaches.

PMID- 12797673
TI  - Current management of acute gastrointestinal bleeding.
AB  - Endoscopic therapy is now the first-line treatment for the management of acute
      ulcer bleeding. Of the many endoscopic methods available, combination treatment
      using adrenaline injection to arrest the active bleeding, followed by thermal or
      electrical coagulation to seal the vessel, is currently the most popular.
      Endoscopic ulcer haemostasis is technically demanding, and indiscriminate
      extrapolation of results of published trials without reference to the expertise
      available locally may be dangerous. The cost-effectiveness of a routine second
      look endoscopy has not been established, but repeat treatment in those who have
      rebled has shown good results in experienced hands. Current evidence supports the
      use of a proton-pump inhibitor to prevent acid-pepsin digestion of the blood clot
      plugging the eroded blood vessel. Interplay between acid, Helicobacter, NSAID and
      'stress' results in peptic ulceration. Eradication of Helicobacter is an
      important measure in the secondary prevention of ulcer bleeding. The inability to
      measure blood flow in the eroded artery before and after treatment, to reliably
      seal a large blood vessel and to detect rebleeding before significant blood loss
      are limiting factors in the current management of ulcer bleeding.

PMID- 12797674
TI  - Options for screening for colorectal cancer.
AB  - Unlike other types of cancer, there are several options for screening for
      colorectal cancer (CRC). The most extensively examined method, faecal occult
      blood testing (FOBT), has been shown, in three large randomized trials, to reduce
      mortality from CRC by up to 20% if offered biennally and possibly more if offered
      every year. Recently published data from the US trial suggest that CRC incidence
      rates are also reduced by up to 20%, but only after 18 years. In this study, the
      number of positive slides was associated with the positive predictive value both
      for CRC and adenomas larger than 1 cm, suggesting that the reduction in CRC
      incidence was caused by the identification and removal of large adenomas. In this
      respect, this study supports the concept that removing adenomas prevents CRC.
      More efficient methods of detecting adenomas include the use of colonoscopy or
      flexible sigmoidoscopy (FS). Considerable evidence exists from case-control and
      uncontrolled cohort studies to suggest that endoscopic screening by sigmoidoscopy
      reduces incidence of distal colorectal cancer. However, in the absence of
      evidence from a randomized trial, several countries have been reluctant to
      introduce endoscopic screening. Three trialsare currently in progress (in the UK,
      Italy and the US) to address this issue. Two of these trials are examining the
      hypothesis that a single FS screen at around age 55-64 might be a cost-effective
      and acceptable method for reducing CRC incidence rates. Recruitment and screening
      are now complete in both studies and the first analysis of results on incidence
      rates is expected in 2004. Colonoscopy screening at 10-year intervals has
      recently been endorsed in the US on the basis that the reductions in incidence
      observed with distal CRC screening can be extrapolated to the proximal colon.
      However, data are lacking and a pilot study for a trial of the acceptability and
      efficacy of colonoscopy screening is in progress in the US. It has also been
      suggested that FOBT testing should be used to detect proximal CRC missed by
      sigmoidoscopy screening, but the small amount of published data suggest that
      supplementing FS with FOBT offers very little advantage over FS alone. Other
      forms of CRC screening are under investigation and represent exciting options for
      the future. Extraction of DNA from stool is now feasible and a number of research
      groups have shown high sensitivity for CRC using a panel of DNA markers including
      mutations in k-ras, APC, p53 and BAT26. Data so far indicate that, with the
      exception of k-ras, these markers are highly specific and therefore represent a
      significant improvement over FOBT. Whether these tests will replace or supplement
      existing methods of screening has yet to be determined. It has been suggested
      that BAT26, which is a marker of microsatellite instability, a feature of
      proximal sporadic CRC, might be a useful adjunct to sigmoidoscopy screening.
      Others have suggested that a test for occult blood should be included with the
      DNA markers to further increase sensitivity. It is not yet known how sensitive
      these markers are for adenomas--it is only by detecting adenomas that CRC
      incidence rates can be reduced. A final exciting new option for screening is
      virtual colonoscopy (VC), which by screening out people without neoplasia allows
      colonoscopy to be reserved for patients requiring a therapeutic intervention. The
      sensitivity of VC for large adenomas and CRC appears to be high, although results
      vary by centre and there is a steep learning curve. Sensitivity for small
      adenomas is low, but perhaps it is less essential to find such lesions. Some
      groups have suggested that virtual colonoscopy might be a useful option for
      investigating patients who test positive with stool-based screening tests.
      Whichever CRC screening method is finally chosen (and there is no reason why
      several methods should not ultimately be available), high quality endoscopy
      resources will always be required to investigate and treat neoplastic lesions
      detected.

PMID- 12797675
TI  - Cost-effectiveness of colorectal cancer surveillance in ulcerative colitis.
AB  - Key issues concerning colorectal cancer in inflammatory bowel disease include
      determination of the risk of colorectal cancer and assessment of interventions to
      increase survival. No randomized, controlled trials of colonoscopic surveillance
      compared to no surveillance exist; however, retrospective studies illustrate that
      surveillance is associated with improved survival, probably as a result of
      detection of cancer at earlier stages of disease. In the absence of prospective
      clinical trials of either prophylactic colectomy or surveillance colonoscopy to
      detect dysplasia, quantitative analysis has been utilized to estimate the impact
      of competing management strategies on costs and benefits. Published analyses show
      that while prophylactic colectomy will likely save the greatest number of life
      years, quality of life is not optimal, and thus shared decision-making between
      provider and patient is recommended. Surveillance colonoscopy to detect early
      cancer and dysplasia appears to be cost-effective, although the risk of
      colorectal cancer must be substantial in order for this to hold true. It is
      estimated that the incidence of cancer in ulcerative colitis must exceed 27% over
      a 30-year period in order for surveillance colonoscopy every 2 years to be cost
      effective. Determination of the optimal interval between surveillance procedures
      is also a contentious issue. Although annual surveillance colonoscopy may not be
      cost-effective, 3-4 year intervals yield cost-effectiveness ratios comparable to
      other medical practices deemed worthwhile by society, while 5-year interval
      produce an incremental cost-effectiveness similar to screening strategies in
      other diseases.

PMID- 12797676
TI  - Gastrointestinal cancer: towards a tailored tumour therapy.
AB  - Major progress has been made in the treatment of metastatic colorectal cancer,
      but conventional chemotherapy is unlikely to lead to a major breakthrough in the
      treatment of gastrointestinal tumours. Prognosticators, novel means of early
      diagnosis of cancer which at the same time indicate prognosis, as well as novel,
      tumour-specific therapeutic strategies, are urgently needed. There is an
      increasing amount of promising data from array technology and functional
      proteomics suggesting that this goal could be achieved in the near future.
      Research into the mechanisms of cancer signal transduction over the past 20 years
      has enabled the identification of numerous novel targets for tumour therapy and
      subsequently the development of various novel drugs termed magic bullets. The in
      vitro results with these drugs are promising; many drugs lost their magic after
      the first clinical trials. The state of novel diagnostics and therapeutics in
      gastrointestinal cancer and the implications for the future treatment of these
      tumours are discussed in this review.

PMID- 12797677
TI  - Genomics in colorectal cancer: godsend or gimmick?
AB  - Genomics and the new techniques it embraces, such as cDNA and tissue arrays,
      comparative genomic hybridization and single nucleotide polymorphism analysis,
      offer the opportunity to generate massive amounts of data relating to screening,
      aetiology, diagnosis, prognostication and optimal treatment in colorectal cancer.
      To make progress, studies must be designed to stringently test these new
      technologies and compare them to the tried and tested gold standards. This is
      best done in the form of large randomized controlled trials. Genomics undoubtedly
      offers the prospect of exciting new developments in the field of colorectal
      cancer but these should be regarded with caution until they are proved superior
      to present practices and models.

PMID- 12797678
TI  - Modern therapy for inflammatory bowel disease.
AB  - Modern therapy for inflammatory bowel disease implies that therapy should be
      disease modifying rather than merely symptomatic. To achieve this goal, induction
      and maintenance of bowel healing are mandatory. Long-term bowel healing results
      in fewer hospitalizations and less surgery. Only immunosuppression therapy and
      biological approaches, or a combination of both, result in long-term healing of
      the bowel mucosa. Unsolved issues are when these drugs should be initiated and
      whether we should aim at eradicating the bowel inflammation from the onset of
      therapeutic intervention immediately following diagnosis. Identification of
      genetic and serologic parameters which allow prediction of the course of the
      disease would be useful for identifying patients who need aggressive treatment
      early in the disease. Once total control of the disease is achieved, long-term
      maintenance of a healed bowel is important. We hypothesize that changing the gut
      flora, e.g. using probiotics, may allow maintenance of bowel healing after
      induction with biologicals and immunosuppression.

PMID- 12797679
TI  - Probiotics: a perspective on problems and pitfalls.
AB  - Therapeutic manipulation of gut flora with probiotics promises to be a useful
      strategy for several disorders, including infectious, inflammatory and neoplastic
      conditions. However, there are large gaps in the knowledge of the normal flora
      and of the optimal use of probiotic products. At present, there is no reliable in
      vitro predictor of in vivo efficacy of putative probiotics. Indeed, probiotic
      performance should be defined in the context of the disease indication for which
      it is intended. This will require rigorous prospective clinical trials. In
      addition, guidelines for routine clinical use of probiotics are confounded by
      insufficient data on optimum strain selection, dose, delivery vehicle and
      monitoring. Before the promise can be fulfilled, problems and potential pitfalls
      with probiotic therapy need resolution.

PMID- 12797680
TI  - Development of virtual histology and virtual biopsy using laser-scanning confocal
      microscopy.
AB  - The aim of this project is to acquire a direct image of histology from in vivo
      gastrointestinal mucosa. In other words, the task of 'endo-microscope' is to
      observe the cellular architecture of tissue in vivo during routine endoscopic
      examination. As the first step to completing this study, resected fresh specimens
      from the oesophagus. stomach and colon were examined by laser-scanning confocal
      microscopy (LCM) (Fluoview, Olympus, Tokyo). Fresh untreated mucosal specimens
      obtained by endoscopic pinch biopsy, polypectomy or endoscopic mucosal resection
      were collected and placed in normal saline and examined by LCM, collecting the
      reflective light of a 488-nm wavelength argon laser beam. As the second step, a
      probe-type LCM 'endo-microscope' was designed and applied to observe the human
      oral-cavity mucosa. The probe has 4.5-mm outer diameter and 20-cm length, which
      enables easy access to oral cavity mucosa. The estimated special resolution of
      the probe is 1-5 microm. A real-time microscopic image directly from ex vivo
      fresh specimens was acquired. The acquired LCM images corresponded well with the
      conventional H-E light microscopic images. Cell wall, nucleus and cytoplasm were
      simultaneously visualized by LCM scanning. This novel method enables serial
      imaginary microscopic sections on fresh specimens. In addition, a probe-type LCM
      'endo-microscope' was designed and was applied to observe human oral cavity
      mucosa. Virtual histological images from the living oral squamous cell were
      successfully obtained. LCM images from ex vivo fresh specimens demonstrated the
      features of the H-E staining histological image. In the next step to accomplish
      our project, we developed a LCM probe with 4.5-mm outer diameter to obtain a
      virtual image of human oral cavity mucosa.

PMID- 12797681
TI  - Management of Barrett's esophagus with and without dysplasia.
AB  - Barrett's esophagus (BE), a premalignant lesion to esophageal adenocarcinoma is
      associated with long-standing, gastroesophageal reflux disease (GERD). BE is a
      multi-phase process: during the initiation phase, genetically predisposed
      individuals (mostly white men) suffering from clinical or occult reflux damage
      their distal esophagus and form a new cell phenotype (incomplete intestinal
      metaplasia). During the formation phase, this phenotype occupies an area of
      variable surface (short or long-segment BE). During the progression phase, the
      metaplastic epithelium either remains dormant or progresses to dysplasia and
      adenocarcinoma. We review the recent clinical and basic research literature that
      explores the interaction of the refluxate (acid, bile, etc.) with BE. Acid and
      bile reflux variably affect BE and may cause dysplasia or adenocarcinoma.
      Regardless of the underlying biology, a patient with BE may suffer from GERD
      symptoms or may remain asymptomatic. Acid may be synergistic to bile or it could
      be antagonistic and protective. Acid suppressive therapy, if profound and
      continuous enough to abolish symptoms and esophageal acid exposure, may decrease
      proliferation, increase differentiation and reduce BE surface. Overexpression of
      cyclooxygenase-2 (COX-2), not entirely independent of acid/bile reflux, may
      increase proliferation and increase the invasiveness and metastatic potential of
      Barrett's metaplasia and neoplasia. Clinically, both acid and bile reflux need to
      be inhibited, either with potent acid-suppressing drugs or anti-reflux surgery.
      Cyclooxygenase inhibition using aspirin, NSAIDs or the safer COX-2 inhibitors
      added to these anti-reflux therapies may enhance the therapeutic benefit. Many
      questions remain unanswered. We still do not know why only a fraction of patients
      with GERD develop BE, what factors of the refluxate (acid, bile, etc.) initiate
      metaplasia and/or promote carcinogenesis, which patients are at risk for
      malignancy, and what is the best chemopreventive strategy. Ablation therapies and
      endoscopic mucosal resection are still under study.

PMID- 12797682
TI  - Resolution of liver cirrhosis and prevention of hepatocellular carcinoma by
      interferon therapy against chronic hepatitis C.
AB  - Hepatocellular carcinoma (HCC) is one of the most important medical problems
      facing the Asian-Pacific region, where the prevalence of chronic hepatitis B and
      C is so high. Every year, we have approximately 500 admissions to our department
      due to this malignancy. It is of utmost importance that we have efficient
      screening, diagnosis and treatment. Over the past several years, there has been
      steady improvement in elucidating the super-high risk group for HCC, and in the
      management of these patients. I discuss how effectively we can screen patients by
      using three tests, conventional AFP, AFP-L3 (lectin fraction) and DCP (des-gamma
      carboxy-prothrombin). With these tests we can detect HCC as small as 10 mm. In
      addition, imaging technology including CT-angiography can effectively pick up
      small cancer nodules. However, they are not always readily available in all Asian
      countries. Thus, diagnostic procedures and treatment methods can be modified in
      each country depending on the situation. One such treatment modality is the
      percutaneous therapy. The recent introduction of radiofrequency ablation (RFA)
      has dramatically changed our daily clinical practice. The time needed to treat
      cancer nodules of 2 to 3 cm in size has been reduced from 1 month or longer with
      ethanol injection to less than a week with RFA. However, the most important issue
      is to prevent infection and progression from chronic hepatitis to HCC. The recent
      introduction of improved antiviral therapy makes us feel optimistically that we
      might eventually have a comprehensive strategy for HCC in the region where it is
      most needed.

PMID- 12797683
TI  - Prefabrication of periosteal graft alone or with oxidised cellulose: an
      experimental study.
AB  - The purpose of this study was to evaluate the feasibility of prefabrication of
      periosteal grafts, alone or with oxidised cellulose (surgicel), which was an
      osteoinductive material using femoral vasculature. Fifteen white New Zealand
      rabbits were used in both femoral regions (30 grafts), and randomly divided into
      three groups including five rabbits (10 grafts): the control group, the
      periosteal graft group, and the periosteal graft+surgicel group. A periosteal
      graft, 30 x 40 mm in size, was obtained from the calvarium of each rabbit. The
      periosteal graft taken was divided into two equal parts, 20 x 30 mm. All these
      periosteal grafts were sutured in the shape of tube. In all rabbits, femoral
      vasculature and periosteal tube was Included in a silicone tube. Additionally, in
      the control group, femoral vasculature was cut above and below the silicone tube,
      whereas in the periosteal graft+surgicel group, surgicel was added to the
      periosteal graft. The results were evaluated macroscopically and
      histopathologically in the second (two rabbits for each group - 4 grafts) and
      fourth week (3 rabbits for each group - 6 grafts). In the second week, In all
      three groups, while no osteoid tissue that indicated osteogenesis developed, it
      was seen that inflammation and increased vascularity occurred. Surgicel was
      observed to be absorbed in the periosteal graft+surgicel group. In the fourth
      week, fibrotic tissue was developed whereas inflammatory tissue disappeared; any
      osteoid tissue or lamellar bone was not accompanied in all three groups. In
      conclusion, we do not believe that periosteum was able to survive as a graft, and
      we found that neovascularization occurred too slowly to preserve the bone forming
      qualities of the periosteum. We suggested that it could not be prefabricated,
      being taken away from its donor site although surgicel was used as a stimulating
      material.

PMID- 12797684
TI  - Congenital blepharoptosis: Part I. Evaluation of the results of surgical
      treatment for congenital blepharoptosis.
AB  - A retrospective clinical analysis of 69 of 118 patients with congenital
      blepharoptosis aged from 2 to 48, who underwent surgical corrections at the
      Department of Plastic Surgery of Lodz between 1977 and 2001, was reviewed.
      Included cases were analysed on the base of the type of primary defect, degree of
      ptosis, and surgical method. The aim of this study was to estimate aesthetic and
      functional results of surgical treatment in 39 patients corrected by Mustarde's
      modified method, in 17 by Mustarde's method, in 7 by Everbusch's method, in 4 by
      Blascovic's method, and in 2 by frontalis suspension. Comparable acceptable
      results of Mustarde's modified and Mustarde's method were achieved.
      Postoperatively 13 patients (18.8%) exhibited lagophthalmos.

PMID- 12797685
TI  - Congenital blepharoptosis: Part II. Visual disorders coexisting with congenital
      blepharoptosis.
AB  - A retrospective ophthalmic analysis 44 of 118 patients with congenital
      blepharoptosis aged from 2 to 48, who underwent surgical correction at the
      Department of Plastic Surgery of Lodz between 1977 and 2001, was reviewed.
      Patients with congenital blepharoptosis were investigated by ophthalmologists in
      the pre and postoperative period, and their medical ophthalmological notes were
      also analysed. The aim of this study was to assess the presence, type, and
      severity of visual disorders coexisting with ptosis. We found in 42 patients
      (95%) ophthalmologic disorders, of which we noted amblyopia in 19, astigmatism in
      30, anisometropia in 5, and strabismus in 30 cases.

PMID- 12797686
TI  - Lipoma of the finger--a case report.
AB  - A rare case of a lipoma occurring in the little finger of a 48-year-old woman is
      described. The presentation and clinical relevance of this and other lipomas
      occurring in the fingers are discussed.

PMID- 12797687
TI  - Influence of inadequate prehospital and primary hospital treatment on the
      maturation of scars after thermal injuries.
AB  - The objective of the work was to verify or rule out the hypothesis on the
      negative effect of incorrect prehospital and primary hospital care on the
      maturation of scars after thermal injuries with a depth of II.b or more. In a
      medium-term study the authors investigated the maturation of scars in children
      aged 3 months to 12 years with different quality of treatment during lay first
      aid, during prehospital and primary hospital care. They focused attention in
      particular on the formation of hypertrophic scars and possibly other
      complications during the functional and aesthetic stabilisation of the scar.

PMID- 12797688
TI  - Facial growth and development during the pubertal period in patients with
      complete unilateral cleft of lip one palate.
AB  - The study is based on a long-term cephalometric follow-up of lateral X-ray films
      of 48 boys with complete unilateral cleft lip and palate during puberty. The
      configuration of the face was negatively influenced by the reduced depth of the
      maxilla and limited vertical growth of the upper lip. As compared with the
      mandible, the maxilla grew less harmoniously in many respects; on the soft
      profile the depth of the nose increased most intensely. Retrusion of the maxilla
      led to a deterioration of sagittal intermaxillary relations in almost 92% of
      patients. In 32% of these patients the deterioration exceeded 3 of the ANB angle,
      and in 27% a transition from the 1st to the 3rd skeletal class was recorded. 25%
      of the subjects already belonged in class III at the age of ten years. In 94% of
      patients during puberty, flattening of the face occurred, which was frequently
      associated with a sunken upper lip (63%). Due to successful orthodontic treatment
      it was possible to restore maxillary overjet in 46% of the patients. In subjects
      who had a maxillary overjet of at least 2 mm at the age of 10 years, it did not
      change to negative values by the age of 15 years. Patients with more severe
      impairment of the jaws were treated more frequently by means of fixed appliances,
      but they did not differ substantially from the other patients in their further
      development (with the exception of a significant anteinclination of the palate).

PMID- 12797689
TI  - War against the virus--who is winning?

PMID- 12797690
TI  - External quality assessment of sputum smear microscopy: a matter of careful
      technique and organisation.

PMID- 12797691
TI  - Is the DOTS strategy sufficient to achieve tuberculosis control in low- and
      middle-income countries? 1. Need for interventions in universities and medical
      schools.
AB  - Now that progress is gradually being made in the implementation of the DOTS
      strategy in low-income countries, we must take into account the fact that nearly
      30% of all tuberculosis (TB) cases worldwide occur in middle-income countries,
      which usually have an adequate health infrastructure and sufficient economic
      resources for TB control. These countries nevertheless have other limitations
      that make it necessary to develop other aspects in addition to the DOTS strategy.
      These can be summarised in three main themes: 1) adequate coordination of all
      health structures involved in TB management, ensuring that they follow the basic
      norms of the National Tuberculosis Programme (NTP), 2) direct intervention in
      universities and medical schools, which are ubiquitous in such countries, and 3)
      specific collaboration with specialists and physicians in private practice, an
      important obstacle to the success of NTPs in several countries. A detailed
      analysis is presented of strategies that need to be implemented in different
      countries depending on their economic resources and their TB situation. The need
      to carry out specific interventions in addition to training in DOTS in
      universities and medical schools in order to improve TB control is discussed. A
      specific project in this area developed by the IUATLD in Latin America is
      described.

PMID- 12797692
TI  - Implementation of proficiency testing in conjunction with a rechecking system for
      external quality assurance in tuberculosis laboratories in Mexico.
AB  - SETTING: In developing countries, tuberculosis is diagnosed by identification of
      acid-fast bacilli (AFB) on sputum smears. OBJECTIVE: To evaluate the quality of
      AFB microscopy, the Mexican Secretary of Health National Reference Laboratory
      implemented proficiency testing for its network of 637 laboratories. DESIGN: A
      total of 586 (92%) laboratories were inspected and 430 technicians evaluated by
      proficiency testing consisting of 10 slides with known numbers of AFB. Results
      were compared with those of slide rechecking and with proficiency testing
      performed 2 years later. RESULTS: Of the 430 technicians evaluated by proficiency
      testing in 1998, 196 (46%) scored less than 80% and received intensive training
      in 1999. From a previous mean score of 65% their results increased to 90% (P <
      0.0001). In 2001, they again underwent proficiency testing, and the mean score
      was 83%. The main factors affecting proficiency testing results were the type of
      laboratory in which the microscopists worked and the number of low-positive
      slides (1-9/100) in the test. Laboratories whose work was rechecked had better
      scores (P = 0.002). Proficiency testing scores and the estimated sensitivity of
      the microscopist's laboratory were associated (P = 0.01). CONCLUSION: External
      quality assessment and training improve diagnostic performance. Rechecking and
      proficiency testing are both viable measures of laboratory performance.

PMID- 12797693
TI  - Quality assurance studies in eight State tuberculosis laboratories in India.
AB  - SETTING: Tuberculosis Research Centre, Chennai, India. OBJECTIVE: To undertake
      quality assurance studies in sputum smear microscopy at eight State-level
      laboratories in India using a panel of stained smears. DESIGN: Coded panels of
      stained smears (100 slides in rounds I-IV and 50 slides in Round V), comprising
      different grades of positivity, were sent to each centre at 6-monthly intervals.
      The results obtained were analysed for consistency of positive and negative
      results and overall agreement, as well as discordance. RESULTS: Consistency of
      positives ranged from 38% to 100%, indicating under-reading at some sites. The
      negative consistency was better, however, with only five of the total of 95
      readers in all rounds yielding a consistency of less than 100%. Considering
      overall agreement, seven of the eight centres showed an agreement of over 90%.
      Four of the eight centres gave no false-positive result. For the remaining
      centres the false positivity rate varied from 2% to 7%. A wide variation was also
      observed in the proportion of false-negatives (3%-52%). CONCLUSIONS: This study
      helped in the evaluation of the performance of individual laboratories and in
      identifying the drawbacks of this system of proficiency testing.

PMID- 12797694
TI  - Annual risk of tuberculous infection in rural areas of Uttar Pradesh, India.
AB  - SETTING: Rural areas in Uttar Pradesh, the most populous state in India.
      OBJECTIVES: 1) To estimate the average annual risk of tuberculous infection
      (ARI), 2) to study ARI trends with age, and 3) to compare tuberculin reactions
      among children with and without BCG scar. STUDY DESIGN: A cross-sectional
      tuberculin survey was conducted among children aged 1-9 years residing in Rae
      Bareli, Hardoi and Jaunpur districts, Uttar Pradesh. Tuberculin testing was
      performed using 1TU of PPD RT23 with Tween 80, and indurations were measured 72
      hours later. Prevalence of infection was estimated in children without BCG scar
      based on the cut-off point identified on the frequency distribution of reaction
      sizes. The ARI was computed from the estimated prevalence. RESULTS: The
      proportion of children with BCG scar varied from 25% to 31% in the study
      districts. Using a cut-off of 14 mm among children without BCG scar, the ARI was
      estimated at 2.3% in Rae Bareli, 1.9% in Hardoi and 1.5% in Jaunpur, and was
      observed to increase with age. Tuberculin test results among children with BCG
      scar suggest that they may be included in tuberculin surveys to estimate ARI.
      CONCLUSION: High rates of transmission of tuberculous infection suggest that
      tuberculosis control measures need to be intensified.

PMID- 12797695
TI  - Annual risk of tuberculous infection in the western zone of India.
AB  - SETTING: Rural and urban areas of six selected districts in the western zone of
      India. OBJECTIVES: To estimate the annual risk of tuberculous infection (ARI).
      DESIGN: A community-based, cross-sectional tuberculin survey was conducted among
      children aged 1-9 years residing in a sample of rural and urban areas of six
      districts in the western zone of India. Stratified two-stage cluster sampling was
      adopted for selection of rural and urban clusters. A total of 48473 children in
      600 clusters underwent tuberculin testing with 1TU PPD RT23 with Tween 80; the
      induration was measured about 72 h after the test. RESULTS: The BCG scar was
      observed in 52% of the test-read children. Estimation of the prevalence of
      infection was based on the frequency distribution of tuberculin reaction size
      among 22259 children without BCG scar. Reactions > or = 15 mm were considered
      attributable to infection with tubercle bacilli. The prevalence of infection was
      estimated to be 9.3%, and the ARI computed from the estimated prevalence was
      1.8%. The proportion of infected children was found to be significantly higher in
      urban than in rural areas. CONCLUSION: The high rate of ARI in the western zone
      of India calls for further intensification of tuberculosis control efforts.

PMID- 12797696
TI  - The private-public divide: impact of conflicting perceptions between the private
      and public health care sectors in India.
AB  - SETTING: India's private health care sector manages half the nation's
      tuberculosis (TB) patients, accounting for an estimated sixth of global TB cases.
      While several studies have demonstrated private physicians' dubious diagnosis and
      treatment styles and lack of cooperation with public physicians, very little is
      still known about the private sector. OBJECTIVES: Using a detailed questionnaire
      to randomly survey private and public practitioners in Ahmedebad, Gujarat, India,
      we quantified perceptions held by each sector. STUDY DESIGN: Cross-sectional
      survey of private and public physicians. RESULTS: Significant conflicts in
      perception were found regarding interpretation of general facts, attitudes
      towards each sector, and effectiveness and social implications of DOTS. We also
      found that such differences in perception were likely to result in mistrust,
      differing views on reform propositions, conflicting mindsets about social
      agendas, and unwillingness to cooperate. CONCLUSION: Our data suggest that
      reconciliation is attainable by obtaining and distributing unbiased, evidence
      based information and exposing physicians to both private and public health care
      sectors in a professional setting.

PMID- 12797697
TI  - Symptoms in patients attending services for diagnosis of pulmonary tuberculosis
      in Sudan.
AB  - OBJECTIVE: To describe the variation in clinical features of individuals
      presenting to a health facility with chest symptoms according to their ultimate
      diagnosis. METHODS: Of 16735 patients (52.6% males and 47.4% females) presenting
      at respiratory centres in seven states in Sudan, 5338 patients were identified
      with respiratory tract symptoms: 2917 (54.6%) men and 2421 (45.4%) women, with a
      mean age of 32 years. Those who had cough for more than 3 weeks that was not
      responsive to a course of antibiotics were screened by microscopy of two or three
      sputum specimens and chest radiography. RESULTS: A total of 504 (9.44%) were
      smear-positive, 259 (4.85%) were smear-negative, and 166 (3.11%) had extra
      pulmonary tuberculosis, of whom 59 (1.11%) had pleural involvement; the remaining
      4409 suspects (82.6%) were non-tuberculous. CONCLUSION: Tuberculosis patients had
      a constellation of presenting symptoms, with the principal symptom being cough
      for more than 3 weeks. The accompanying symptoms with greatest predicted
      significance were weight loss, tiredness and night sweats.

PMID- 12797698
TI  - Is the risk of occupational tuberculosis higher for young health care workers?
AB  - SETTING: Health care workers in Finland. OBJECTIVE: Occupational tuberculosis
      (TB) was studied separately in nurses, assistant nurses, physicians, psychiatric
      nurses, medical laboratory workers and radiographers during the period 1971-1995.
      DESIGN: All 447 notified cases between 20 and 59 years of age were included.
      Incidence ratios by age and occupation were compared to the corresponding general
      population. RESULTS: A common profile, with a higher rate of TB towards older
      age, was seen in the general population but not among health care workers. Among
      nurses, assistant nurses and physicians, the incidence ratio was higher among
      those aged 20-39 than among those aged 40-59 years. Compared to the controls, the
      risk of TB was significantly smaller in the older group of nurses during 1971
      1990 and in assistant nurses during 1971-1995. The risk among the older group of
      physicians was significantly lower during 1971-1980, and among the younger group
      it was significantly higher during 1976-1990. CONCLUSIONS: We speculate that in
      certain fields of health care, young workers are at the greatest risk of TB.

PMID- 12797699
TI  - The high value of high-resolution computed tomography in predicting the activity
      of pulmonary tuberculosis.
AB  - SETTING: A 2500-bed medical centre in southern Taiwan. OBJECTIVE: To study the
      clinical value of high-resolution computed tomography (HRCT) in predicting the
      activity of pulmonary tuberculosis (TB). DESIGN: HRCTs were performed
      prospectively in 148 patients whose chest radiographs (CXRs) showed highly
      suspicious signs of pulmonary TB, predominantly upper lung field infiltration.
      The HRCT findings, interpreted independently by a pulmonologist and a
      radiologist, were used to predict the activity of pulmonary TB. RESULTS:
      Pulmonologist-interpreted and radiologist-interpreted HRCTs showed high
      sensitivity (both 93%), specificity (83 vs. 88%), accuracy (86 vs. 90%), positive
      predictive values (76 vs. 83%) and negative predictive values (both 95%). Kappa
      statistic indicates good inter-reader agreement. CONCLUSION: HRCT has a high
      value in predicting the activity of pulmonary TB. It is a useful tool in this
      regard when a patient with suspected pulmonary TB lacks microbiologic proof, when
      clinical condition makes invasive diagnosis impossible or when a patient has
      completed anti-tuberculosis treatment with no compatible unequivocal CXR.

PMID- 12797700
TI  - Comparative evaluation of the BACTEC MGIT 960 system with solid medium for
      isolation of mycobacteria.
AB  - SETTING: The utilisation of new, rapid methods of diagnosis of tuberculosis is
      currently of great interest for tuberculosis control. This study was carried out
      in a teaching hospital in the eastern region of Taiwan. OBJECTIVE: The BACTEC
      MGIT 960 system was evaluated and compared with Lowenstein-Jensen (LJ) medium and
      Middlebrook 7H11 plate for recovery rate and time to detection of mycobacteria.
      DESIGN: A total of 1396 sputum samples were tested for the presence of
      mycobacteria. Specimens were processed and inoculated separately in the BACTEC
      MGIT 960 system, on LJ medium and 7H11 for comparative study. RESULTS: The BACTEC
      MGIT 960 detected 235 isolates (100%), followed by LJ with 205 isolates (87.2%)
      and 7H11 with 178 isolates (75.7%). The mean time to detection of Mycobacterium
      tuberculosis complex was 11.6 days with MGIT 960, 20.1 days with LJ, and 18.7
      days with 7H11. The contamination rates were 15.1% with MGIT 960, 10.1% with LJ
      and 9.7% with 7H11. CONCLUSION: The BACTEC MGIT 960 system is a sensitive, rapid
      mycobacterial culturing system. However, the high contamination rate is a concern
      that should be carefully evaluated in the clinical setting.

PMID- 12797701
TI  - Impact of iron loading on the activity of isoniazid or ethambutol in the
      treatment of murine tuberculosis.
AB  - OBJECTIVE: To assess the impact of iron loading on the activity of isoniazid and
      ethambutol in the treatment of murine tuberculosis. DESIGN: Iron-loaded and iron
      normal female Balb/C mice infected with 1.5 x 10(7) colony forming units of
      Mycobacterium tuberculosis were treated with either isoniazid or ethambutol for
      28 days. RESULTS: For both treatments, the outcome was impaired by the iron
      loading: bactericidal activity of isoniazid was partially but significantly
      reduced and ethambutol bactericidal activity was totally inhibited. CONCLUSION:
      The treatment of tuberculosis in patients with iron loading should be longer than
      for normal patients or should contain an additional drug.

PMID- 12797702
TI  - Evaluation of the polymerase chain reaction in the diagnosis of miliary
      tuberculosis in bone marrow smear.
AB  - OBJECTIVE: Miliary tuberculosis (MTB) is difficult to diagnose. When prompt
      diagnosis is necessary, the polymerase chain reaction (PCR) to detect
      mycobacterial DNA may be valuable. SETTING: Tuberculosis clinic in an academic
      tertiary-level hospital in Mexico. DESIGN: Bone marrow (BM) aspiration samples
      from 30 consecutive clinically suspected MTB patients and 58 non-tuberculosis
      hematologic patients were evaluated by in-house PCR using a fragment of the
      insertion sequence IS6110; results were compared with those obtained by acid-fast
      stained smears, culture in Lowenstein-Jensen medium, histology, and serology.
      RESULTS: Tuberculosis diagnosis was confirmed in all MTB suspects, 28 by
      microscopy and culture in pulmonary or extra-pulmonary samples other than BM, and
      two by clinical and radiologic improvement after antituberculosis treatment. In
      fresh BM specimens, in-house PCR was positive in 21/30 (70%) suspects,
      contrasting with only one positive (3.3%) in staining and culture, and four with
      compatible histologic findings (13.3%). BM samples from the control group showed
      negative results in bacteriologic and histologic studies, except in nine who had
      positive PCR results. These nine control cases had malignant processes.
      CONCLUSION: PCR in aspirates of BM is a useful diagnostic assay in cases of MTB,
      mainly when bacteriological results are negative.

PMID- 12797703
TI  - The clearance of theophylline is increased during the initial period of
      tuberculosis treatment.
AB  - OBJECTIVE: To evaluate the effects of combined anti-tuberculosis treatment
      including isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide
      (PZA), on the pharmacokinetics of theophylline during the initial phase of
      treatment. DESIGN: Prospective, controlled clinical study. PATIENTS AND METHODS:
      Twenty patients with pulmonary tuberculosis received 7.35 mg/kg/day of
      aminophylline intravenously combined with anti-tuberculosis agents. The first
      theophylline serum concentration was measured before administration of INH, RMP,
      EMB and PZA, and samples were obtained once daily for 6 consecutive days after
      initiation of treatment. All patients in this study were non-smokers with normal
      hepatic and renal function, and they were not given any other drugs that could
      affect the clearance of theophylline. RESULTS: The concentration and half-life of
      theophylline was decreased and its clearance was increased significantly at days
      5-7 after administration of antituberculosis agents compared to before the
      therapy was started. CONCLUSIONS: These results suggest that patients with asthma
      or chronic obstructive pulmonary disease administered combinations of anti
      tuberculosis agents and theophylline during the initial phase of tuberculosis
      treatment should be monitored closely for changes in theophylline concentration,
      and that the dose of theophylline should be adjusted accordingly.

PMID- 12797705
TI  - Variants of the human NRAMP1 gene and susceptibility to tuberculosis in Morocco.
AB  - It has been well established that the host genetic background is an important
      modulator of tuberculosis susceptibility. The NRAMP1 (alias SLC11A1) gene has
      been associated with tuberculosis susceptibility in several ethnic groups. Here
      we studied the association and linkage of NRAMP1 with tuberculosis in 116 nuclear
      families, comprising 211 affected offspring, from Casablanca, Morocco. All
      enrolled tuberculosis cases were culture-positive. No evidence was found of
      linkage or association of NRAMP1 with tuberculosis. These findings suggest
      heterogeneity in the genetic control of tuberculosis susceptibility.

PMID- 12797704
TI  - The asthma programme of Finland: an evaluation survey in primary health care.
AB  - OBJECTIVE: To evaluate the basic structures and processes of asthma care 6 years
      after the launch of the Finnish Asthma Programme. The evaluation will serve as
      the baseline for the implementation of the evidence-based guidelines for asthma
      published in 2000. DESIGN: A descriptive type-2 evaluation (managerial monitoring
      of a policy implementation), based on operationalised statements of the Asthma
      Programme. RESULTS: A co-ordinating doctor for asthma, usually a general
      practitioner (GP), was interviewed in 248 (91%) health centres; 83% of the health
      centres have at least one GP nominated as the local asthma co-ordinator and 94%
      have a nurse. Asthma education for the professionals had been organised in 71% of
      the health centres in the previous 2 years. First-line treatment consists of an
      inhaled corticosteroid. Guided self-management is used in 98% of the health
      centres, but its components were not clear to the doctors. CONCLUSION: The basic
      structure of equipment and organisation for the diagnosis and treatment of asthma
      has been set up in the primary health care services.

PMID- 12797706
TI  - Ethambutol sensitivity test.

PMID- 12797707
TI  - The disciplinary background of the IJTLD editorial board.

PMID- 12797709
TI  - Validity and feasibility of the use of condition-specific outcome measures in
      economic evaluation.
AB  - BACKGROUND: Usually, generic questionnaires such as the EQ-5D or Health Utility
      Index (HUI) are used to obtain utility scores for computing QALYs. Sometimes,
      however, application of these instruments is not possible, or the responsiveness
      is doubted. An alternative strategy is to attribute utility scores to health
      states of a condition-specific outcomes measure (CSOM). We explored the validity
      and feasibility of this strategy. RESEARCH DESIGN: Our samples determined utility
      scores for the health states of the International Index of Erectile Function
      (IIEF) using time tradeoff (TTO). To reduce costs and time, the general
      population (n = 169) was interviewed in groups. We tested the validity of the
      group sessions in students. To test the extent of agreement between values
      obtained using the group and those obtained through individual administration, 63
      students were interviewed individually and 54 in groups. RESULTS: The utility
      scores for the disease-specific health states showed good construct validity.
      Also, the criterion validity of the adapted TTO was confirmed. DISCUSSION:
      Disease-specific utility scores can be used in QALY analysis by converting them
      to a generic scale. Efforts should be undertaken to prevent response spreading.
      Administrating TTO in groups could reduce the time and costs of TTO
      administration and render the strategy of determining utilities for condition
      specific health states more feasible.

PMID- 12797710
TI  - Use of differential item functioning analysis to assess the equivalence of
      translations of a questionnaire.
AB  - In cross-national comparisons based on questionnaires, accurate translations are
      necessary to obtain valid results. Differential item functioning (DIF) analysis
      can be used to test whether translations of items in multi-item scales are
      equivalent to the original. In data from 10,815 respondents representing 10
      European languages we tested for DIF in the nine translations of the EORTC QLQ
      C30 emotional function scale when compared to the original English version. We
      tested for DIF using two different methods in parallel, a contingency table
      method and logistic regression. The DIF results obtained with the two methods
      were similar. We found indications of DIF in seven of the nine translations. At
      least two of the DIF findings seem to reflect linguistic problems in the
      translation. 'Imperfect' translations can affect conclusions drawn from cross
      national comparisons. Given that translations can never be identical to the
      original we discuss how findings of DIF can be interpreted and discuss the
      difference between linguistic DIF and DIF caused by confounding, cross-cultural
      differences, or DIF in other items in the scale. We conclude that testing for DIF
      is a useful way to validate questionnaire translations.

PMID- 12797708
TI  - On assessing responsiveness of health-related quality of life instruments:
      guidelines for instrument evaluation.
AB  - A lack of clarity exists about the definition and adequate approach for
      evaluating responsiveness. An overview is presented of different categories of
      definitions and methods used for calculating responsiveness identified through a
      literature search. Twenty-five definitions and 31 measures were found. When
      applied to a general and a disease-specific quality of life questionnaire large
      variation in results was observed, partly explained by different goals of
      existing methods. Four major issues are considered to claim the usefulness of an
      evaluative health-related quality of life (HRQL) instrument. Their relation with
      responsiveness is discussed. The confusion about responsiveness arises mostly
      from a lack of distinction between cross-sectional and longitudinal validity and
      from a lack of distinction between responsiveness defined as the effect of
      treatment and responsiveness defined as the correlation of changes in the
      instrument with changes in other measures. All measures of what is currently
      called responsiveness can be looked at as measures of longitudinal validity or as
      measures of treatment effect. The latter ones tell us little about how well the
      instrument serves its purpose and are only of use in interpreting score changes.
      We therefore argue that the concept of responsiveness can be rejected as a
      separate measurement property of an evaluative instrument.

PMID- 12797711
TI  - New technology in quality of life research: are all computer-assisted approaches
      created equal?
AB  - OBJECTIVE: To compare alternate form reliability for two previously validated
      questionnaires using traditional and computer-assisted interfaces (CASI).
      METHODS: The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the
      allergy-specific Work Productivity and Activity Impairment (WPAI) instrument were
      combined and formatted for paper-and-pencil (P), computer touch screen (TS), or
      web-based (WB) administration. Employees at a large midwestern hospital in the US
      each completed two of three possible formats assigned randomly and in random
      order. Those completing one of three possible format pairs (P-TS, P-WB, and TS
      WB) comprised three study groups. Item response consistency was assessed using
      Spearman correlations; individuals' test-retest scores were compared using paired
      t-tests with mean test-retest differences compared between groups using ANOVA.
      RESULTS: Seventy five volunteers completed 150 questionnaires. Item response
      consistency varied by format pair with correlations ranging from 0.566 to 0.973.
      Although no differences were observed in paired RQLQ responses, participants
      completing the WB form reported generally higher WPAI scores compared with those
      from either the paper (p = 0.07) or TS (p = 0.001) format. ANOVA of mean RQLQ and
      WPAI scores demonstrated no between-group differences. CONCLUSIONS: Use of CASI,
      an increasingly popular method in survey research, may have important effects on
      instrument reliability. Studies examining this phenomenon more closely are needed
      to guide future use of CASI in this setting.

PMID- 12797712
TI  - Cancer patients' preferences for communicating clinical trial quality of life
      information: a qualitative study.
AB  - Health-related quality of life (HRQL) is a prevalent outcome measure in clinical
      trials, but it is not known how best to communicate HRQL results to new patients
      with cancer. The purpose was to explore cancer patients' attitudes toward, and
      preferences for, 10 visual and written formats for communicating HRQL
      information. Using standardized qualitative methods, six focus groups were held
      (two groups in each of three cancer centres) with patients who had completed
      treatment for cancer at least 6 months earlier. Groups were stratified according
      to patients' education. To ensure consistency across centres, group moderators
      used the same detailed guide, training video, and props. Three investigators
      independently coded the resulting transcripts. Participants also rated each of
      the 10 presentation formats as to their perceived usefulness. Fourteen men and 19
      women with a variety of cancer diagnoses participated; 13 (39%) participated in
      the three lower-education groups and 20 (61%) in the three higher-education
      groups. We found that simple formats (simple graphs or written text) were
      generally preferred to more complex graphical information, regardless of
      educational level. The same format was rated favourably by the highest proportion
      of participants in both the high (85%) and low (85%) education level groups.
      Individual patients, however, varied as to which visual format they most
      preferred. Patients did not wish to receive HRQL information out of context or
      without explanation. We conclude that cancer patients desire HRQL information,
      but vary in their preferences for its communication. Simple formats are generally
      preferred.

PMID- 12797713
TI  - Physical and mental health: changes during menopause transition.
AB  - OBJECTIVE: To measure changes in physical and mental health in six groups of
      women defined by menopausal status or use of hormone replacement therapy (HRT).
      DESIGN: Longitudinal study with 2 years follow-up. PARTICIPANTS: Eight thousand
      six hundred and twenty three women participating in the Australian Longitudinal
      Study on Women's Health, aged 45-50 years in 1996. MAIN OUTCOME MEASURES: Changes
      in the eight dimensions of the Short Form General Health Survey (SF-36) adjusted
      for baseline scores, lifestyle, behavioural and demographic factors. RESULTS: At
      baseline, mean scores for five of the eight dimensions of the SF-36 were highest
      (indicating better state of health or well-being) in premenopausal women. There
      were declines (that is, worsening health) in the SF-36 dimensions in most groups
      of women. Declines were largest in physical functioning (adjusted mean change of 
      4.9, standard error (SE) 0.7) and physical role limitation (-5.7, SE: 1.3) in
      women who remained peri-menopausal throughout the study period and in women
      taking HRT at the time of either survey (physical functioning: -5.3 (0.7), role
      physical limitation: -7.5 (1.2)). They were smallest in women who remained pre
      menopausal (physical functioning: -3.2 (0.7); role physical limitation: -2.1
      (1.1)). CONCLUSIONS: Physical aspects of general health and well-being decline
      during the menopausal transition. Sensitive measures and careful analysis are
      needed to understand why these changes are worse for peri-menopausal women and
      those taking HRT.

PMID- 12797714
TI  - The effect of prandial glucose regulation with repaglinide on treatment
      satisfaction, wellbeing and health status in patients with pharmacotherapy naive
      Type 2 diabetes: a placebo-controlled, multicentre study.
AB  - This prospective, 16-week, randomised, double-blind, parallel-group study
      assessed the differential impact of the prandial glucose regulating oral
      hypoglycaemic drug, repaglinide, and placebo upon perceptions of quality of life
      (QoL) and treatment satisfaction in pharmacotherapy-naive patients with Type 2
      diabetes. In addition, the study assessed whether these outcomes were influenced
      by the patients' level of glycaemic control. A total of 253 patients were
      randomised in a 2:1 ratio of repaglinide: placebo, with doses taken flexibly with
      main meals (2-4 per day), whenever they were eaten. Repaglinide was initiated at
      0.5 mg per meal, increased to 1 mg after 4 weeks if fasting plasma glucose
      exceeded 7.8 mmol/l. QoL and treatment satisfaction outcomes were compared using
      generic and disease-specific self-assessment measures, previously applied in
      diabetes: the WHO Wellbeing Questionnaire (WHO-WBQ), WHO Diabetes Treatment
      Satisfaction Questionnaire (WHO-DTSQ) and EuroQoL EQ-5D. Over the trial period,
      repaglinide-treated patients reported a significant 9% improvement in (WHO-DTSQ)
      treatment satisfaction score (p < 0.05). No significant increase was associated
      with placebo. The correlation between decrease in glycated haemoglobin (HbA1c)
      and increase in treatment satisfaction (WHO-DTSQ) was -0.22 (p < 0.01). Scores
      obtained with the other measures did not change significantly during the trial in
      either group, but the cohort exhibited only a slight reduction in wellbeing (WHO
      WBQ) and health status (EQ-5D) at baseline compared with the background
      population. In conclusion, flexible mealtime dosing with oral medication appears
      to be well accepted by pharmacotherapy-naive patients with Type 2 diabetes. The
      results suggest that repaglinide provides a higher level of treatment
      satisfaction than placebo, and this may in part relate to improved glycaemic
      control.

PMID- 12797715
TI  - Multinational study of reliability and validity of the King's Health
      Questionnaire in patients with overactive bladder.
AB  - OBJECTIVE: Overactive bladder (OAB) has substantial impact on health-related
      quality of life (HRQoL). The purpose of this research was to evaluate the
      psychometric properties of the King's Health Questionnaire (KHQ). METHODS: The
      KHQ (n = 1284) was administered at baseline and 12 weeks post-treatment in a
      multinational, double-blind, randomized clinical trial of tolterodine for
      treatment of OAB. Country-specific psychometric analyses of HRQoL instruments
      were performed. Countries demonstrating marginal psychometric properties on the
      KHQ were pooled with same-language countries, re-evaluated, and aggregate
      analysis performed on the pooled data. RESULTS: Internal consistency of the KHQ
      was high, item characteristics were good, most assumptions of summed scales were
      met, and it is externally valid and consistent. Few problems with the KHQ were
      noted although the performance of the personal relationships domain was
      complicated by the 'not applicable' response category. CONCLUSIONS: Psychometric
      testing supports the reliability and validity of the KHQ as an OAB-specific
      measure of HRQoL.

PMID- 12797716
TI  - Quality of life in Taiwanese adults with chronic rhino-sinusitis.
AB  - BACKGROUND AND PURPOSE: Chronic rhino-sinusitis (CRS) is a disease in prevalence.
      This study evaluates the impact of this disorder to Taiwanese patients' general
      and sinus-related health status among Taiwanese patients with CRS. METHODS: A
      total of 201 consecutive CRS patients (male:female: 107:94, mean age: 40.1 +/-
      14.6 years) seeking otolaryngological care at a tertiary referral medical center
      were recruited. Quality of life was measured by a Taiwan Standard Version of the
      Medical Outcome Study 36-Item Short Form Health Survey (SF-36) and a Chinese
      version Chronic Sinusitis Survey (CCSS). Patients were administered with the SF
      36 and CCSS preoperatively. RESULTS: CRS has a significant impact on patients in
      seven of the eight domains of SF-36: role-physical (88.9 +/- 24.7), bodily pain
      (70.3 +/- 22.6), general health (56.1 +/- 11.6), social functioning (79.3 +/-
      21.6), vitality (56.4 +/- 19.1), role-emotional (57.7 +/- 42.1), and mental
      health (48.4 +/- 17.2) subscores of CRS patients are all in significant decrement
      (p < 0.05) as compared with the data derived from Taiwanese general population.
      Physical functioning is the only domain without impact. Significant decrements (p
      < 0.05) are also observed in symptom subscale (43.3 +/- 27.8), medication
      subscale (80.3 +/- 26.4), and total survey score (63 +/- 20.3) of the CCSS as
      compared to the healthy subjects. The severity of CRS is significantly predictive
      (p < 0.05, R2 = 0.34) of CCSS. CONCLUSIONS: CRS has considerable impacts on a
      patient's sinus-related quality of life, as well as on their general health
      status.

PMID- 12797717
TI  - Equivalence of Chinese and US-English versions of the SF-36 health survey.
AB  - This study evaluated the equivalence of Chinese and US-English versions of the SF
      36 Health Survey in a convenience sample of 309 Chinese nationals bilingual in
      Chinese and English living in a US city. Snowball sampling was used to generate
      sufficient sample size. Internal consistency, test-retest, and equivalent-forms
      reliability were estimated. Patients were randomized to one of four groups: (1)
      English version completed first, followed by Chinese version (same occasion); (2)
      Chinese version completed first, followed by English version (same occasion); (3)
      English version completed once and then again 1-week later; (4) Chinese version
      completed once and then again 1-week later. Internal consistency reliability
      estimates for the Chinese and US-English versions of the SF-36 scales ranged from
      0.60 to 0.88; test-retest reliability estimates (1 week time interval) ranged
      from 0.67 to 0.90. Reliability estimates for corresponding Chinese and US-English
      SF-36 scales tended to be similar and not significantly different. Equivalent
      forms reliability estimates (product-moment correlations) ranged from 0.81 to
      0.98. Mean SF-36 scale scores were comparable for both versions of the
      instrument. This study provides support for the equivalence of the Chinese and US
      English versions of the SF-36.

PMID- 12797718
TI  - Measuring disease specific quality of life in localized prostate cancer: the
      Dutch experience.
AB  - OBJECTIVE: We aimed at developing and testing a Dutch health-related quality of
      life measure for localized prostate cancer patients. METHODS: Scales on urinary
      and bowel function and bother from the UCLA Prostate Cancer Index (PCI) underwent
      formal linguistic and cultural translation. PCI sexual scales were replaced by an
      existing Dutch sexual activities module (SAc). After qualitative pilot testing
      389 patients with localized prostate cancer (mean age 67 +/- 7 years) completed
      the measure before and at 2 time points after primary treatment. Psychometric
      properties (feasibility, score distribution, reliability, construct validity and
      responsiveness to change) of the new instrument were analyzed. RESULTS: Response
      rates ranged from 93% at baseline to 87% after treatment. Urinary and bowel
      function scales showed Cronbach's alphas >0.7. Urinary function and bother, and
      bowel function and bother were significantly correlated. Pre- vs. post
      prostatectomy effect sizes were >0.9 only for urinary scales; while pre- vs. post
      radiotherapy effect sizes were >0.75 only for bowel scales. Six months after
      baseline erectile dysfunction was reported by 64% of respondents, either as a
      problem in sexual activity or as a reason for not being sexually active.
      CONCLUSION: The Dutch PCI and SAc performed well in men treated for early stage
      prostate cancer.

PMID- 12797719
TI  - Strategies for improving neural signal detection using a neural-electronic
      interface.
AB  - There have been various theoretical and experimental studies presented in the
      literature that focus on interfacing neurons with discrete electronic devices,
      such as transistors. From both a theoretical and experimental perspective, these
      studies have emphasized the variability in the characteristics of the detected
      action potential from the nerve cell. The demonstrated lack of reproducible
      fidelity of the nerve cell action potential at the device junction would make it
      impractical to implement these devices in any neural prosthetic application where
      reliable detection of the action potential was a prerequisite. In this study, the
      effects of several different physical parameters on the fidelity of the detected
      action potential at the device junction are investigated and discussed. The
      impact of variations in the extracellular resistivity, which directly affects the
      junction seal resistance, is studied along with the impact of variable nerve cell
      membrane capacitance and variations in the injected charge. These parameters are
      discussed in the context of their suitability to design manipulation for the
      purpose of improving the fidelity of the detected neural action potential. In
      addition to investigating the effects of variations in these parameters, the
      applicability of the linear equivalent circuit approach to calculating the
      junction potential is investigated.

PMID- 12797720
TI  - Pattern identification and perceived stimulus quality as a function of
      stimulation waveform on a fingertip-scanned electrotactile display.
AB  - The effect of stimulation waveform on pattern perception was investigated on a 49
      point fingertip-scanned electrotactile (electrocutaneous) display. Waveform
      variables burst frequency (F), number of pulses per burst (NPB), and pulse
      repetition rate (PRR) were varied in a factorial design. Contrast reduction was
      used to limit performance of perceiving a 1-tactor gap defined within a 3 x 3
      tactor outline square. All three variables accounted for significant variations
      in performance with higher levels of F and NPB and lower levels of PRR, leading
      to better performance. In addition, we collected qualitative data on each
      waveform, and the qualitative differences were related to performance (e.g.,
      waveforms perceived as having a more localized sensation were correlated with
      better pattern identification performance than those waveforms perceived as more
      broad). We also investigated the effect of stimulation contrast on pattern
      perception.

PMID- 12797721
TI  - Assessment of muscle fatigue during biking.
AB  - The analysis of the surface myoelectric signal recorded while a muscle is
      performing a sustained contraction is a valuable tool for assessing the
      progression of localized fatigue. It is well known that the modifications of the
      spectral content of the myoelectric signal are mainly related to changes in the
      interstitial fluid pH, which, in turn, affect the membrane excitability of the
      active muscle fibers. This paper describes the effects of muscle fatigue on the
      surface myoelectric signal recorded from three thigh and leg muscles during
      biking, on a population consisting of 22 young healthy volunteers. The purpose of
      this study was to obtain normative data relative to an exercise protocol mild
      enough to be applicable, in the future, to pathological subjects as well. Each
      subject was asked to exercise 30 min on a cycloergometer at a constant velocity
      and against a constant torque. While subjects were biking, the surface
      myoelectric signal was recorded from the rectus femoris, the biceps femoris, and
      the gastrocnemius muscles. In this study, we considered two different aspects of
      muscle fatigue: first, the localized muscle fatigue as shown by the decrement of
      the instantaneous frequency of the myoelectric signal during the exercise;
      second, the modifications of the muscle ON-OFF timing, which could be explained
      as a strategy for increasing endurance by modifying the role of different muscles
      during the exercise. The first aspect was studied by obtaining the spectral
      characteristics of the signals by means of bilinear time-frequency transforms and
      by applying an original estimator of the instantaneous frequency of stochastic
      processes based on cross time-frequency transforms. Our results demonstrated that
      none of the subjects showed significant signs of localized muscle fatigue, since
      the decrement of the instantaneous frequency during the exercise was always lower
      than 5% of its initial value. Muscle ON-OFF timing was obtained by applying to
      the raw myoelectric signal a double threshold statistical detector to identify
      the time intervals during which the observed muscles were active. This
      demonstrated that the subjective feeling of fatigue each subject reported during
      the exercise did not cause a change of the activation strategy of the observed
      muscles. It is concluded that the experimental protocol herein described and the
      signal processing procedures adopted are appropriate for monitoring different
      effects of muscle fatigue during biking. Moreover, data obtained from our sample
      population can be considered as a reference for studying the manifestations of
      muscle fatigue in pathological subjects asked to follow a similar experimental
      protocol.

PMID- 12797722
TI  - Continuous curve registration as an intertrial gait variability reduction
      technique.
AB  - Timing in peak values shifts slightly between gait trials. When gait data are
      averaged, part of the standard deviation could be associated with this intertrial
      variability unless normalization is carried out beforehand. The objective of this
      study was to determine how continuous curve registration, an alignment technique,
      can reduce intersubject variability in gait data without altering the original
      curve characteristics. Gait data were obtained by means of a four-camera high
      speed video system synchronized to a force plate. The data for 60 gait trials
      were collected from 20 young, healthy subjects. Curve registration was applied to
      hip angular displacement, net moment, and power curves generated in the sagittal
      plane. Following registration, the peak values increased by an average of 1.2%
      (0.11 +/- 0.26 degrees) for angular displacement, and by 11.2% (0.11 +/- 0.09
      W/kg) for power, while there were no changes for moments. First and second
      derivatives of the unregistered and registered curves did not display significant
      differences, and the harmonics were barely affected. Continuous curve
      registration would thus be an appropriate technique for application prior to any
      statistical analysis using able-bodied gait patterns.

PMID- 12797723
TI  - Estimation of the 3-D center of mass excursion from force-plate data during
      standing.
AB  - Biomechanical models are used with force-plate information to determine the
      center of mass (COM) trajectory during standing. They are usually based on
      simplifying assumptions and are often limited to a single-plane analysis. The
      objectives of this study were to present a three-dimensional (3-D) model to
      calculate the excursion of the COM of the human body, validate it and compare its
      performance to a video-based system during quiet standing and antero-posterior
      (AP) and medio-lateral (ML) self-imposed oscillations. In addition to the
      vertical displacements of the COM, the originality of the method lies in
      eliminating the accelerations terms in the model and their related assumptions.
      The model was able to estimate closely the COM displacements in quiet standing [a
      root mean square (RMS) of 0.9 mm or less]. For the self-imposed oscillations, the
      RMS differences were 6.6 mm in the AP and ML directions and 1.6 mm along the
      vertical axis. For all three testing conditions, the coefficients of correlation
      of the COM displacements between the model and the video methods were above 0.8
      with the exception of the vertical direction, where the values were more
      variable.

PMID- 12797724
TI  - A miniaturized neuroprosthesis suitable for implantation into the brain.
AB  - This paper presents current research on a miniaturized neuroprosthesis suitable
      for implantation into the brain. The prosthesis is a heterogeneous integration of
      a 100-element microelectromechanical system (MEMS) electrode array, front-end
      complementary metal-oxide-semiconductor (CMOS) integrated circuit for neural
      signal preamplification, filtering, multiplexing and analog-to-digital
      conversion, and a second CMOS integrated circuit for wireless transmission of
      neural data and conditioning of wireless power. The prosthesis is intended for
      applications where neural signals are processed and decoded to permit the control
      of artificial or paralyzed limbs. This research, if successful, will allow
      implantation of the electronics into the brain, or subcutaneously on the skull,
      and eliminate all external signal and power wiring. The neuroprosthetic system
      design has strict size and power constraints with each of the front-end
      preamplifier channels fitting within the 400 x 400-microm pitch of the 100
      element MEMS electrode array and power dissipation resulting in less than a 1
      degree C temperature rise for the surrounding brain tissue. We describe the
      measured performance of initial micropower low-noise CMOS preamplifiers for the
      neuroprosthetic.

PMID- 12797725
TI  - Nonlinear elastic material property estimation of lower extremity residual limb
      tissues.
AB  - The interface stresses between the residual limb and prosthetic socket have been
      studied to investigate prosthetic fit. Finite-element models of the residual limb
      prosthetic socket interface facilitate investigation of the mechanical interface
      and may serve as a potential tool for future prosthetic socket design. However,
      the success of such residual limb models to date has been limited, in large part
      due to inadequate material formulations used to approximate the mechanical
      behavior of residual limb soft tissues. Nonlinear finite-element analysis was
      used to simulate force-displacement data obtained during in vivo rate-controlled
      (1, 5, and 10 mm/s) cyclic indentation of the residual limb soft tissues of seven
      individuals with transtibial amputation. The finite-element models facilitated
      determination of an appropriate set of nonlinear elastic material coefficients
      for bulk soft tissue at discrete clinically relevant test locations. Axisymmetric
      finite-element models of the residual limb bulk soft tissue in the vicinity of
      the test location, the socket wall and the indentor tip were developed
      incorporating contact analysis, large displacement, and large strain, and the
      James-Green-Simpson nonlinear elastic material formulation. Model dimensions were
      based on medical imaging studies of the residual limbs. The material coefficients
      were selected such that the normalized sum of square error (NSSE) between the
      experimental and finite-element model indentor tip reaction force was minimized.
      A total of 95% of the experimental data were simulated using the James-Green
      Simpson material formulation with an NSSE less than 5%. The respective James
      Green-Simpson material coefficients varied with subject, test location, and
      indentation rate. Therefore, these coefficients cannot be readily extrapolated to
      other sites or individuals, or to the same site and individual some time after
      testing.

PMID- 12797726
TI  - Implementation of a telemonitoring system for the control of an EEG-based brain
      computer interface.
AB  - By the use of a brain-computer interface (BCI), it is possible for completely
      paralyzed patients, who have lost their ability to speak, to have a new
      possibility to communicate with their environment. The training with such a BCI
      system can be performed at the patient's home, if there is a responsible person
      present who is familiar with the system. This person has to adjust different
      parameters and to adapt the training individually to each patient. Since this
      function is usually taken over by the developers of the system, the number of
      patients who can be included in regular BCI training is restricted due to
      geographical distances. This paper describes the implementation of a
      telemonitoring system, which makes it possible for the developer to control and
      supervise the BCI training from his or her own place of work. First experiences
      with a patient living far away from the developer's lab are reported.

PMID- 12797727
TI  - Evaluation of adaptive/nonadaptive filtering and wavelet transform techniques for
      noise reduction in EMG mobile acquisition equipment.
AB  - The myoelectric signal can be used to control many rehabilitation systems, for
      instance, prostheses and artificial neuromuscular electrical stimulation toward
      restoring movement to spinal cord injured subjects. These mobile systems are
      usually used in different environments and thus are being exposed to different
      noise levels with characteristics not completely known. In this article, three
      main techniques for noise reduction were evaluated: wavelet transform (WT),
      adaptive digital filters, and nonadaptive digital filters. The WT was used to
      reconstruct the signal with the components without noise information. Adaptive
      filters were designed using least mean square (LMS) and recursive least square
      (RLS) algorithms. Finite-impulse response (FIR) and infinite-impulse response
      (IIR) nonadaptive filters were used for comparison to both the adaptive filters
      and the signal reconstruction through the WT.

PMID- 12797728
TI  - A general framework for brain-computer interface design.
AB  - The Brain-Computer Interface (BCI) research community has acknowledged that
      researchers are experiencing difficulties when they try to compare the BCI
      techniques described in the literature. In response to this situation, the
      community has stressed the need for objective methods to compare BCI
      technologies. Suggested improvements have included the development and use of
      benchmark applications and standard data sets. However, as a young,
      multidisciplinary research field, the BCI community lacks a common vocabulary. As
      a result, this deficiency leads to poor intergroup communication, which hinders
      the development of the desired methods of comparison. One of the principle
      reasons for the lack of common vocabulary is the absence of a common functional
      model of a BCI System. This paper proposes a new functional model for BCI System
      design. The model supports many features that facilitate the comparison of BCI
      technologies with other BCI and non-BCI user interface technologies. From this
      model, taxonomy for BCI System design is developed. Together the model and
      taxonomy are considered a general framework for BCI System design. The
      representational power of the proposed framework was evaluated by applying it to
      a set of existing BCI technologies. The framework could effectively describe all
      of the BCI System designs tested.

PMID- 12797729
TI  - Development of an enzyme-linked immunosorbent assay for the detection of the
      organophosphorus insecticide acephate.
AB  - A competitive indirect enzyme-linked immunosorbent assay (ciELISA) for the
      organophosphorus insecticide acephate, O,S-dimethyl acetylphosphoramidothioate,
      was developed using a polyclonal antibody. Five different haptens mimicking the
      analyte were synthesized and conjugated with the carrier proteins bovine serum
      albumin (BSA) and keyhole limpet hemocyanin (KLH) by the N-hydroxysuccinimide
      active ester and diazotization methods. Polyclonal antibodies raised against
      hapten-KLH conjugates in rabbits and hapten-BSA conjugates as coating antigens
      were screened and selected for the assay in the homologous and heterologous ELISA
      systems. The effects of various assay conditions such as detergent, organic
      solvents, pH, and preincubation of the mixture of the polyclonal antibody and the
      analyte on the sensitivity were evaluated. The IC(50) value for acephate was 25
      ng/mL in an optimized heterologous system using hapten-4-BSA as a coating antigen
      and a polyclonal antibody no. 8377 against hapten-1-KLH, showing the detection
      range of 5-140 ng/mL and the lowest detection limit of 2 ng/mL. The cross
      reactivities of the structurally related organophosphorus insecticides, including
      the major metabolite of the analyte, methamidophos, were less than 1%. Recoveries
      from the analyte-fortified tap water, mulberry leaves, and lettuce samples in the
      assay were in the range of 72-121% by simple extraction, concentration, and
      dilution. These results indicate that the ELISA could be a convenient and
      supplemental analytical tool for monitoring acephate residues in environmental
      and agricultural samples.

PMID- 12797730
TI  - Capillary gas chromatography with atomic emission detection for pesticide
      analysis in soil samples.
AB  - A method for the simultaneous determination of 10 pesticides (organochlorines,
      organophosphorus compounds, and pyrethrins) in soils using capillary gas
      chromatography with atomic emission detection (GC-AED) is reported. Soil samples
      are first "cleaned-up" with 25 mL of an ascorbic acid solution (pH 2.15). The
      aqueous phase is extracted with ethyl acetate, and the solid residue is then
      extracted twice with 10 mL of ethyl acetate. The three resultant organic extracts
      are combined, concentrated to dryness, and reconstituted in 1 mL of acetone. The
      pesticides are selectively detected by monitoring chlorine and bromine in the
      first run and sulfur emission line wavelength in the second run. Each
      chromatographic run takes 19 min. Detection limits are between 25 and 75 pg,
      depending on the compound, which corresponds to 1.7 and 5.0 ng/g in the soil
      samples, respectively. Recoveries of the pesticides from spiked preparations
      result in an overall mean recovery of 95.3% (n = 120) at fortification levels
      ranging from 10 to 60 ng/g, depending on the compound. The method is reliable and
      can be useful for routine monitoring in soils.

PMID- 12797731
TI  - Analysis of bitter limonoids in citrus juices by atmospheric pressure chemical
      ionization and electrospray ionization liquid chromatography-mass spectrometry.
AB  - Improved analytical techniques for bitter limonoids in citrus and citrus juices
      can expedite the evaluation of freeze-induced citrus damage for citrus growers
      and juice quality for citrus juice producers. Microbore normal-phase and reverse
      phase chromatography coupled to a mass spectrometer operating in a positive ion
      atmospheric pressure chemical ionization and electrospray ionization modes were
      found to be rapid, selective, and sensitive methods for the analysis of the
      bitter limonoids limonin and nomilin in citrus juices. Analysis was performed on
      a chloroform extract of citrus juice to which an internal standard was added. The
      methods are capable of detecting citrus limonoids in citrus juice in the 60-200
      picogram range and quantifying citrus juice limonoids in concentrations as low as
      120 picograms. An accurate "total limonoid bitterness" in citrus juice, as
      represented by the combined occurrence of limonin and nomilin, is easily
      determined by these methods.

PMID- 12797732
TI  - Determination of ractopamine in cattle and sheep urine samples using an optical
      biosensor analysis: comparative study with HPLC and ELISA.
AB  - A biosensor method, using the surface plasmon resonance (SPR) principle, was
      developed for the determination of ractopamine in cattle and sheep urine. A
      monoclonal antibody was used to compete with ractopamine in the sample and
      ractopamine immobilized on the sensor chip. Addition of bovine serum albumin
      (BSA, 1 mg/mL) as an antibody stabilizer to the incubation buffer was required to
      achieve a stable biosensor response throughout each sample set. The calibration
      curve gave a mean IC(50) of 4.7 +/- 0.21 ng/mL (n = 7). Over sample
      concentrations from 2.5 to 10 ng/mL recoveries were typically approximately 100
      110%, whereas inter- and intra-assay reproducibilities (% CV) were usually less
      than 10 and 6%, respectively. Comparison of biosensor results with results
      obtained from high-performance liquid chromatography (HPLC) and enzyme-linked
      immunosorbent assays (ELISA) using enzyme-hydrolyzed urine (to convert
      ractopamine conjugates to free ractopamine) gave correlation coefficients of 0.94
      for sheep and 0.86 for cattle. Slopes of the lines, with zero intercepts, equaled
      0.80 for sheep and 0.74 for cattle. For untreated (nonhydrolyzed) urine samples,
      the correlations between biosensor and HPLC results were 0.95 for sheep and 0.72
      for cattle with slopes of 1.18 (sheep) and 1.69 (cattle). The slopes greater than
      unity indicate that the biosensor responded to ractopamine metabolites in
      addition to free ractopamine. The biosensor assay is an excellent analytical tool
      to screen ractopamine residues in sheep or cattle urine, and the results should
      be extendible to other species with suitable validation.

PMID- 12797733
TI  - Determination of selenium in nuts by cathodic stripping potentiometry (CSP).
AB  - The aim of this work was to determine the selenium content in nut samples by
      cathodic stripping potentiometry. Dry-powdered nuts were digested by HNO(3) and
      dissolved with concentrated hydrochloric acid. To avoid the interference of
      natural oxygen, the potentiometric determination of selenium was carried out in
      an electrolyte solution consisting of 2 M CaCl(2) and 4 M HCl. The analysis was
      executed applying an electrolysis potential of -150 mV for 60 s and a constant
      current of -30 microA. Under these conditions, detection limits lower than 1.0 ng
      g(-)(1) were obtained for selenium analysis in nuts. The relative standard
      deviation of these measurements (expressed as rsd %) ranged from 0.44 to 0.88%
      while recoveries ranged from 90.2 to 95.3%. The results obtained with the
      proposed method were compared with those obtained via hydride vapor generation
      atomic absorption spectroscopy, a common method for determining selenium. The
      results of the two methods agreed within 5% for almond, hazelnut, and pistachio
      samples. The mean concentrations of selenium determined in Sicilian samples of
      almond, hazelnut, and pistachio were 531 +/- 1, 865 +/- 1, and 893 +/- 4
      microg/kg, respectively.

PMID- 12797734
TI  - A mass spectrometric validated high-performance liquid chromatography procedure
      for the determination of folates in foods.
AB  - A series of five food reference materials (RM) that had certified values of
      folate concentrations and five frozen food samples were analyzed for 5
      methyltetrahydrofolic acid (5-MTHFA) and folic acid (FA) using a high-performance
      liquid chromatography (HPLC) method with fluorescence detection that was
      validated using an HPLC mass spectrometry (MS) method with electrospray
      ionization. Identical sample specimens were extracted and analyzed in triplicate
      using both instrumental methods, and a comparison was made of the mean values of
      5-MTHFA and FA resulting from these determinations. The analytes were isolated on
      either a high capacity strong anion exchange solid phase extraction column (HPLC
      method) or a phenyl Bond Elut column (MS method) prior to analyses. For
      quantification of the analytes by MS, (13)C-labeled 5-MTHFA and FA were added to
      samples as internal standards prior to enzymatic digestion and conversion of the
      polyglutamate forms of 5-MTHFA to the monoglutamic acid. Quantification of FA and
      5-MTHFA using the HPLC analysis was carried out using external standards. With
      the exception of one RM (pig liver), the values established for 5-MTHFA using
      these methods were highly comparable. In determining the variance associated with
      these two procedures, it was observed that the mean relative standard error for 5
      MTHFA was 12 (range, 2-27%) and 11% (range, 5-25%) for the HPLC and MS methods,
      respectively. FA was detected in only three of the samples, and the values
      obtained for it by either method were similar. This is the first paper that
      describes a mass spectrometric method used in the validation of an HPLC
      determination of food folates across a wide range of sample matrixes. The
      comparable values for 5-MTHFA and FA suggest that HPLC analysis with fluorescent
      detection may be used to accurately quantify folates present in a variety of food
      matrixes.

PMID- 12797735
TI  - High-affinity monoclonal antibodies for detection of the microbial metabolite, 2
      methylisoborneol.
AB  - The production of 2-methylisoborneol (MIB) by certain fungi and algae can
      contribute musty off-flavors to foods and water supplies if uncontrolled. The
      goal of this research was to develop a nonsensory simple method for the detection
      of MIB. Anti-MIB monoclonal antibodies were produced by immunizing mice with
      borneol-conjugated protein and selecting positive clones with an MIB-protein
      conjugate. An indirect competitive immunoassay developed using this antibody had
      a detection limit of 0.6 microg L(-)(1) and an I(50) value of 5 microg L(-)(1).
      Detection was relatively specific for MIB and showed 20% cross-reactivity with
      borneol or isoborneol and 4-5% cross-reactivity with camphor. No cross-reactivity
      to geosmin was observed.

PMID- 12797736
TI  - Determination of free proline and monosaccharides in wine samples by high
      performance anion-exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD).
AB  - A sensitive and selective analytical method for the simultaneous separation and
      quantitative determination of proline and free monosaccharides in wine samples by
      high-performance anion-exchange chromatography coupled with pulsed amperometric
      detection is described. Under optimized experimental conditions, a complete
      separation was obtained in less than 30 min, using an isocratic elution with 10
      mM NaOH and 1 mM Ba(OAc)(2). No postcolumn addition of strong bases to the eluent
      for enhancing detection sensitivity was needed. Upon 25-fold sample dilution and
      purification to avoid interference of tannins, pigments, and phenolic compounds,
      the fingerprinting of common monosaccharides (i.e., arabinose, glucose, fructose,
      galactose, and xylose) and proline in wines, musts, and vinegars can be easily
      accomplished. The method allows high recovery and satisfies the necessary
      requirements for accuracy, repeatability, and sensitivity. Values obtained for
      proline content ranged from 470 to 1190 mg/L in "Aglianico" red wines (mean
      value, 870 +/- 192 mg/L, n = 21) and from 168 to 286 mg/L in white wines (mean
      value, 208 +/- 32 mg/L, n = 11). Lower levels were found in musts of red and
      white grapes, 550 and 87 mg/L, respectively. The lowest content of proline, ca.
      10 mg/L, was found both in white and red vinegars.

PMID- 12797737
TI  - Spectrophotometric and adsorptive stripping square wave voltammetric
      determination of iron in olive oils, as complex with 5,5-dimethylcyclohexane
      1,2,3-trione 1,2-dioxime 3-thiosemicarbazone (DCDT).
AB  - Two methods for the determination of iron in olive oil by spectrophotometry and
      by adsorptive stripping square wave voltammetry (Ad-SSWV) have been developed.
      These two methods are based on the formation of a 5,5-dimethylcyclohexane-1,2,3
      trione 1,2-dioxime 3-thiosemicarbazone (DCDT)-iron(II) complex in strongly acid
      media. In both, iron is extracted from the olive oil by using HCl.
      Spectrophotometric determination of iron with DCDT is based on the feature that
      the DCDT-Fe complex shows an absorbance maximum at 550 nm. A calibration graph
      has been constructed from 0 to 4000 ng mL(-)(1), and the detection limit was 115
      ng mL(-)(1) (57 ng g(-)(1) in olive oil). On the other hand, the voltammetric
      determination of the metal is based on the appearance of a peak due to an
      adsorptive reductive process of the complex that it is observed when the Ad-SSWV
      technique is used. A calibration graph has been constructed from 0 to 30 ng mL(
      )(1), and the detection limit was 0.55 ng mL(-)(1) (13.75 ng g(-)(1) in olive oil
      according to the proposed procedure).

PMID- 12797738
TI  - Interlaboratory comparison of extraction efficiency of pesticides from surface
      and laboratory water using solid-phase extraction disks.
AB  - A continuation of an earlier interlaboratory comparison was conducted (1) to
      assess solid-phase extraction (SPE) using Empore disks to extract atrazine,
      bromacil, metolachlor, and chlorpyrifos from various water sources accompanied by
      different sample shipping and quantitative techniques and (2) to compare
      quantitative results of individual laboratories with results of one common
      laboratory. Three replicates of a composite surface water (SW) sample were
      fortified with the analytes along with three replicates of deionized water (DW).
      A nonfortified DW sample and a nonfortified SW sample were also extracted. All
      samples were extracted using Empore C(18) disks. After extraction, part of the
      samples were eluted and analyzed in-house. Duplicate samples were evaporated in a
      2-mL vial, shipped dry to a central laboratory (SDC), redissolved, and analyzed.
      Overall, samples analyzed in-house had higher recoveries than SDC samples.
      Laboratory x analysis type and laboratory x water source interactions were
      significant for all four compounds. Seven laboratories participated in this
      interlaboratory comparison program. No differences in atrazine recoveries were
      observed from in-house samples analyzed by laboratories A, B, D, and G compared
      with the recovery of SDC samples. In-house atrazine recoveries from laboratories
      C and F were higher when compared with recovery from SDC samples. However,
      laboratory E had lower recoveries from in-house samples compared with SDC
      samples. For each laboratory, lower recoveries were observed for chlorpyrifos
      from the SDC samples compared with samples analyzed in-house. Bromacil recovery
      was <65% at two of the seven laboratories in the study. Bromacil recoveries for
      the remaining laboratories were >75%. Three laboratories showed no differences in
      metolachlor recovery; two laboratories had higher recoveries for samples analyzed
      in-house, and two other laboratories showed higher metolachlor recovery for SDC
      samples. Laboratory G had a higher recovery in SW for all four compounds compared
      with DW. Other laboratories that had significant differences in pesticide
      recovery between the two water sources showed higher recovery in DW than in the
      SW regardless of the compound. In comparison to earlier work, recovery of these
      compounds using SPE disks as a temporary storage matrix may be more effective
      than shipping dried samples in a vial. Problems with analytes such as
      chlorpyrifos are unavoidable, and it should not be assumed that an extraction
      procedure using SPE disks will be adequate for all compounds and transferrable
      across all chromatographic conditions.

PMID- 12797739
TI  - Determination and confirmation of 5-hydroxyflunixin in raw bovine milk using
      liquid chromatography tandem mass spectrometry.
AB  - A method was developed and validated to determine 5-hydroxyflunixin in raw bovine
      milk using liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean
      recovery and percentage coefficient of variation (%CV) of 35 determinations for 5
      hydroxyflunixin was 101% (5% CV). The theoretical limit of detection was 0.2 ppb
      with a validated lower limit of quantitation of 1 ppb and an upper limit of 150
      ppb. Accuracy, precision, linearity, specificity, ruggedness, and storage
      stability were demonstrated. A LC/MS/MS confirmatory method using the extraction
      steps of the determinative method was developed and validated for 5
      hydroxyflunixin in milk from cattle. Briefly, the determinative and confirmatory
      methods were based on an initial solvent (acetone/ethyl acetate)
      precipitation/extraction of acidified whole milk. The solvent
      precipitation/extraction effectively removed incurred ((14)C) residues from milk
      samples. The organic extract was then purified by solid phase extraction (SPE)
      using a strong cation exchange cartridge (sulfonic acid). The final SPE-purified
      sample was analyzed using LC/MS/MS. The methods are rapid, sensitive, and
      selective and provide for the determination and confirmation of 5-hydroxyflunixin
      at the 1 and 2 ppb levels, respectively.

PMID- 12797740
TI  - Insecticidal activity and chemical composition of volatile oils from Hyptis
      martiusii Benth.
AB  - The essential oils from leaves and inflorescences of Hyptis martiusii Benth were
      analyzed by GC-MS. Twenty-six compounds representing 93.2% of the essential oil
      of leaves were characterized; Delta-3-carene (22.5%), 1,8-cineole (24.27%), beta
      caryophyllene (6.15%), and bicyclogermacrene (6.32%) were found as the major
      components. In the essential oil of inflorescences 27 compounds representing
      87.7% of the oil were identified. The major components were Delta-3-carene
      (13.5%), alpha-pinene (5.78%), beta-caryophyllene (6.59%), viridiflorene (8.25%),
      and germacrene B (5.21%). The essential oil of leaves and 1,8-cineole showed
      pronounced insecticidal effect against Aedes aegypti larvae and Bemisia
      argentifolii, the vectors of dengue fever and white fly fruit plague,
      respectively.

PMID- 12797741
TI  - Suppression of allergic reactions by dehulled adlay in association with the
      balance of TH1/TH2 cell responses.
AB  - Dehulled adlay is known as a natural Chinese medicine having antiallergic
      activity, although its mechanism remains unclear. This study examined the effects
      of dehulled adlay on antigen-specific antibody and cytokine production. Mice were
      immunized three times with ovalbumin (OVA) in alum adjuvant. It was found that
      oral administration of dehulled adlay in mice suppressed the production of IgE
      against OVA antigen. Serum anti-OVA IgG(2a) antibody levels were significantly
      increased in mice after oral administration of dehulled adlay. Furthermore, the
      production of IL-2 by OVA-stimulated splenocytes was augmented in dehulled adlay
      fed mice. Although dehulled adlay had no effect on the serum anti-OVA IgG(1)
      antibody levels, it had a great capacity to reduce IL-5 secretion by means of OVA
      stimulated splenocytes. Hydrothermal processes, including steaming and extrusion
      cooking, did not change the capacity of dehulled adlay to suppress IgE
      production. Three fractions of dehulled alday, including methanolic extract, warm
      water extract, and residue, were obtained. The methanolic extract exhibited the
      greatest capacity to reduce anti-OVA IgE production. These results suggest that
      dehulled adlay has a modulating ability to shift the balance from Th2 to Th1
      dominance in the T cell mediated immune system and may be beneficial for the
      treatment of allergic disorders.

PMID- 12797742
TI  - TAXI type endoxylanase inhibitors in different cereals.
AB  - An affinity-based purification procedure with the immobilized family 11 Bacillus
      subtilis endoxylanase XynA allowed us to obtain high yields of highly pure
      endoxylanase inhibitor fractions from rye, barley, and durum wheat. In contrast,
      no inhibitors interacting with the B. subtilis endoxylanase affinity column are
      present in corn, buckwheat, rice, and oats. Sodium dodecyl sulfate polyacrylamide
      gel electrophoresis analysis and inhibitor specificity showed that the isolated
      inhibitors belonged to the TAXI endoxylanase inhibitor family, thus providing a
      view on the diversity of this cereal inhibitor family. The isolated inhibitors
      are basic proteins of ca. 40 kDa, occurring in two molecular forms, with pI
      values of ca. 8.5 (durum wheat) and ca. 9.0 (rye, barley). They are, in general,
      strong inhibitors of family 11 endoxylanases but not of family 10 endoxylanases.
      Because cereal endogenous endoxylanases belong to the latter family, this
      probably indicates that they do not influence cereal metabolic processes. For the
      first time, endoxylanase inhibitors, similar to TAXI I and TAXI II from wheat,
      were isolated from durum wheat and characterized. For each cereal, high
      resolution cation exchange chromatography revealed the presence of multiple
      isoinhibitors, each of which occurs in two molecular forms. However, in durum
      wheat and barley, a single isoform is predominantly present.

PMID- 12797743
TI  - Changes in broccoli (Brassica oleracea L. Var. italica) health-promoting
      compounds with inflorescence development.
AB  - Changes in phenolic compounds, total glucosinolates, and vitamin C were monitored
      during the productive period along five inflorescence development stages of three
      broccoli commercial cultivars (Marathon, Monterrey, and Vencedor). In an attempt
      to identify differences due to agronomic factors, broccoli cultivars were grown
      under different sulfur fertilization with poor (15 kg/ha) and rich (150 kg/ha)
      rates. Phenolic compounds and vitamin C concentrations showed, in all broccoli
      cultivars, a rising trend from the first stage until the over-maturity stage,
      both for rich and poor sulfur fertilization. Significant differences were
      detected in the first two stages between rich and poor sulfur fertilization in
      total glucosinolates for all broccoli cultivars, where the highest concentration
      was always observed in the second development stage (used as minimally processed
      product) during poor fertilization. With regard to the last three stages, the
      glucosinolate concentration in the poor sulfur fertilization started to slope
      down until the over-maturity stage. Where rich sulfur fertilization is concerned,
      the highest level was reached during the third stage (used as minimally processed
      product also), and after that, glucosinolate concentration decreased until the
      fifth stage.

PMID- 12797744
TI  - Analysis of the lectins from teosinte (Zea diploperennis) and maize (Zea mays)
      coleoptiles.
AB  - To identify molecular evidence of the common origin of maize and teosinte, a
      lectin from teosinte coleoptile (TCL) was purified, through affinity
      chromatography on a lactosyl-Sepharose column, and some of the physicochemical
      parameters were compared with those from the maize coleoptile lectin (CCL). TCL
      is a 92 kDa glycoprotein constituted mainly by aspartic, glutamic, glycine,
      leucine, and lysine residues; in minor proportion, methionine and cysteine were
      also found. The glycannic portion of the lectin, which corresponds to 10% w/w, is
      composed by Gal, Man, and GlcNAc. CCL is an 88.7 kDa glycoprotein that contains
      12% sugars by weight; its sugar and amino acid compositions are similar to those
      of TCL. TCL is formed by two isoforms identified through acidic electrophoresis,
      whereas CCL is constituted by a single molecular form. The NH(2) termini of both
      TCL isoforms are blocked, but their amino acid sequences determined from tryptic
      peptides by matrix-assisted laser desorption ionization time-of-flight) indicated
      that TCL isoforms have no homology with other mono- or dicotyledonous lectins,
      including CCL. TCL, just as CCL, showed hemagglutinating activity toward animal
      erythrocytes, including human A, B, and O. Hapten inhibition assays indicated
      that although TCL shows broader sugar specificity than CCL, it recognizes Gal in
      O- and N-glycosidically linked glycans. Both lectins are equally well recognized
      by antibodies against TCL.

PMID- 12797745
TI  - Turkish Tombul hazelnut (Corylus avellana L.). 1. Compositional characteristics.
AB  - The quality of Tombul (Round) hazelnut, grown in the Giresun province of Turkey,
      was determined by measuring proximate composition, minerals, vitamins, dietary
      fiber, amino acids, and taste active components (free amino acids, sugars, and
      organic acids). Fat was the predominant component in Tombul hazelnut
      (approximately 61%). The major minerals were potassium, phosphorus, calcium,
      magnesium, and selenium. Hazelnut was also found to serve as an excellent source
      of vitamin E (24 mg/100 g) and a good source of water soluble (B complex)
      vitamins and dietary fiber. The major amino acids were glutamic acid, arginine,
      and aspartic acid. The three nonessential amino acids and the essential amino
      acids contributed 44.9 and 30.9% to the total amino acids present, respectively,
      while lysine and tryptophan were the limiting amino acids in Tombul hazelnut.
      Twenty-one free amino acids, six sugars, and six organic acids were positively
      identified; among these, arginine, sucrose, and malic acid predominated,
      respectively. These taste active components may play a significant role in the
      taste and flavor characteristics of hazelnut. Thus, the present results suggest
      that Tombul hazelnut serves as a good source of vital nutrients and taste active
      components.

PMID- 12797746
TI  - Turkish Tombul hazelnut (Corylus avellana L.). 2. Lipid characteristics and
      oxidative stability.
AB  - The quality of crude hazelnut oil extracted from Tombul (Round) hazelnut, grown
      in the Giresun province of Turkey, was determined by measuring lipid classes,
      fatty acids, and fat soluble bioactives (tocopherols and phytosterols). Oxygen
      uptake, peroxide value, thiobarbituric acid reactive substances, and alpha
      tocopherol levels of stripped and crude hazelnut oils in bulk and oil-in-water
      (o/w) emulsion systems were also evaluated as indices of lipid oxidation over a
      21 day storage period at 60 degrees C in the dark. The total lipid content of
      Tombul hazelnut was 61.2%, of which 98.8% were nonpolar and 1.2% polar
      constituents. Triacylglycerols were the major nonpolar lipid class and
      contributed nearly 100% to the total amount. Phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylinositol were the most abundant polar
      lipids, respectively. Sixteen fatty acids were identified, among which oleic acid
      contributed 82.7% to the total, followed by linoleic, palmitic, and stearic
      acids. Unsaturated fatty acids accounted for 92.2% of the total fatty acids
      present. Among oil soluble bioactives, alpha-tocopherol (38.2 mg/100 g) and beta
      sitosterol (105.5 mg/100 g) were predominant in hazelnut oil and comprised 88 and
      93% of the total tocopherols and phytosterols present, respectively. The results
      also showed that both stripped and crude hazelnut oils were more stable in terms
      of lipid oxidation in the bulk oil as compared to those in an o/w emulsion.

PMID- 12797747
TI  - Isolation and structural elucidation of some procyanidins from apple by low
      temperature nuclear magnetic resonance.
AB  - Procyanidin fractions from apple were separated according to the degree of
      polymerization using normal phase chromatography. Evaluation of physiological
      functionalities of procyanidins requires individual structural determination.
      However, it is difficult to elucidate the structure of procyanidins, in
      particular those with (+)-epicatechin (1) or (-)-catechin (2) units, and
      determine whether the interflavanoid bonds are 4beta-->8 or 4beta-->6 without
      cleavage and acetylation. Structural determination used LC-MS and low-temperature
      NMR. Nine procyanidins were separated by preparative HPLC consisting of three
      well-known procyanidins [procyanidin B1 (3), procyanidin B2 (4), and procyanidin
      C1 (5)] and six new procyanidins [epicatechin-(4beta-->8)-epicatechin-(4beta-->8)
      catechin (6); epicatechin-(4beta-->6)-epicatechin-(4beta-->8)-catechin (7);
      epicatechin-(4beta-->6)-epicatechin-(4beta-->8)-epicatechin (8); epicatechin
      (4beta-->8)-epicatechin-(4beta-->6)-catechin (9); epicatechin-(4beta-->8)
      epicatechin-(4beta-->6)-epicatechin (10); and epicatechin-(4beta-->8)-epicatechin
      (4beta-->8)-epicatechin-(4beta-->8)-epicatechin (11)]. Compounds 6-11 were
      detected for the first time as apple constituents.

PMID- 12797748
TI  - Effect of cyclodextrin glycosyl transferase [corrected] on dough rheology and
      bread quality from rice flour.
AB  - Gluten-free breads are usually characterized by deficient quality characteristics
      as compared to wheat breads. Problems related to volume and crumb texture are
      associated with gluten-free breads even when rice flour is used, which seems to
      be the best raw material for this type of bread. The potential use of
      cyclodextrin glycosyl transferase (CGTase) as a rice bread improver is presented.
      The effect of CGTase addition to rice flour on dough rheology and bread quality
      was investigated. In addition, an experimental design was developed to optimize
      the levels of CGTase, hydroxypropylmethylcellulose (HPMC), and oil. The addition
      of CGTase produced a reduction in the dough consistency and also in the elastic
      modulus. With regard to the rice bread quality, better specific volume, shape
      index, and crumb texture were obtained. The amount of cyclodextrins in the bread
      crumb was quantified to explain the action of this enzyme. The data indicate that
      the improving effect of the CGTase results from a combination of its hydrolyzing
      and cyclizing activities, the latter being responsible for the release of
      cyclodextrins, which have the ability to form complexes with lipids and proteins.

PMID- 12797749
TI  - Heat-induced changes in the susceptibility of egg white proteins to enzymatic
      hydrolysis: a kinetic study.
AB  - A kinetic study was conducted on the effect of heating in the temperature range
      of 50-92 degrees C, on the susceptibility of ovalbumin and albumen solutions to
      enzymatic hydrolysis by a mixture of trypsin and alpha-chymotrypsin at 37 degrees
      C and pH 8.0. Heat treatment resulted in an increase in degree of hydrolysis
      after 10 min of enzymatic reaction of both ovalbumin and albumen, as measured
      using the pH-stat method. The time-dependent change in the susceptibility to
      enzymatic hydrolysis after heat treatment was described by a fractional
      conversion model (based on an apparent first-order reaction kinetic model).
      Different end levels of degree of hydrolysis were obtained after heating for a
      long time at different temperatures, which suggests that the final degree of
      unfolding of the protein is temperature dependent.

PMID- 12797750
TI  - Activity of quinones on colletotrichum species.
AB  - The antifungal activity of 1,4-naphthoquinones, 1,2-naphthoquinones, 1,4
      benzoquinones, and anthraquinones from our natural products collection was tested
      by direct bioautography to identify natural products with potential use in
      agricultural fungal pathogen control. Quinones demonstrated good to moderate
      antifungal activity against Colletotrichum spp. Colletotrichum fragariae was the
      most sensitive species to quinone-based chemistry, Colletotrichum gloeosporioides
      had intermediate sensitivity, while Colletotrichum acutatum was the species least
      sensitive to these compounds.

PMID- 12797751
TI  - Examination of molecular interaction sites of acetanilides with organic matter
      surrogates using nuclear magnetic resonance techniques.
AB  - The dynamics of acetanilide pesticide interactions with organic matter (OM)
      surrogates were examined using nuclear magnetic resonance (NMR) spectroscopy.
      Differences in the relative changes in (13)C and (1)H spin-lattice relaxation
      times (T(1)) were measured at multiple molecular sites of metolachlor and the
      probe compound acetanilide to identify interaction sites and/or surfaces between
      the molecules and dissolved and colloidal OM surrogates. The decrease in T(1) at
      specific sites of acetanilide molecules was a function of the OM used and its
      concentration. High-affinity interactions at nonaromatic sites of metolachlor and
      acetanilide were observed with cellulose, chitin, and collagen, but interactions
      with lignin occurred with less site specificity and involved both aromatic and
      nonaromatic sites of the molecules. Changes in relaxation were compared to
      calculated and experimentally determined binding coefficients (K(oc)). The T(1)
      relaxation of the aromatic sites of acetanilides showed better relations with
      K(oc) than the nonaromatic sites. This study shows that NMR relaxation
      measurements can identify the high-affinity molecular interaction sites of
      acetanilides to OM surrogates.

PMID- 12797752
TI  - Characterization of volatiles in bullock's heart (Annona reticulata L.) fruit
      cultivars from Cuba.
AB  - Volatile compounds were isolated from four cultivars of bullock's heart fruit
      (Cenizo, Rojo, Verde, and De Ojo) by simultaneous steam distillation-solvent
      extraction. Compounds were identified by HRGC and capillary GC-MS. One hundred
      and eighty compounds were identified in the aroma extracts, of which alpha
      pinene, beta-pinene, myrcene, limonene, terpinen-4-ol, and germacrene D were
      found to be the major constituents. Fruit from cv. De Ojo containing the highest
      concentration of total volatile and the highest major terpenoid content had the
      highest custard-like and overall fruity aroma intensity. The presence of many
      terpenic compounds is thought to contribute to the unique flavor of the bullock's
      heart fruit.

PMID- 12797753
TI  - Sensory and instrumental evaluation of catnip (Nepeta cataria L.) aroma.
AB  - The present study investigates the composition of volatile constituents and
      sensory characteristics of catnip (Nepeta cataria L.) grown in Lithuania.
      Hydrodistillation, simultaneous distillation-solvent extraction, static
      headspace, and solid phase microextraction methods were used for the isolation of
      aroma volatiles. Geranyl acetate, citronellyl acetate, citronellol, and geraniol
      were the major constituents in catnip. Differences in the quantitative
      compositions of volatile compounds isolated by the different techniques were
      considerable. A sensory panel performed sensory analysis of the ground herb, pure
      essential oil, and extract; aroma profiles of the products were expressed
      graphically, and some effects of odor qualities of individual compounds present
      in catnip on the overall aroma of this herb were observed.

PMID- 12797754
TI  - Chemical composition and antibacterial activity of essential oils from Thymus
      spinulosus Ten. (Lamiaceae).
AB  - The chemical composition of essential oils from aerial parts of Thymus spinulosus
      Ten. (Lamiaceae) is reported. Four oils from plants growing in different
      environmental conditions were characterized by GC and GC-MS methods; the oils
      seem to indicate a new chemotype in the genus Thymus. Influences of soil and
      altitude characteristics on the essential oil composition are discussed. The oils
      showed antibacterial activity against Gram-positive (Staphylococcus aureus,
      Streptococcus faecalis, Bacillus subtilis, and Bacillus cereus) and Gram-negative
      (Proteus mirabilis, Escherichia coli, Salmonella typhimuium Ty2, and Pseudomonas
      aeruginosa) bacteria.

PMID- 12797755
TI  - Composition, quality control, and antimicrobial activity of the essential oil of
      long-time stored dill (Anethum graveolens L.) seeds from Bulgaria.
AB  - The essential oil of long-time stored seeds of dill (Anethum graveolens L.) from
      Bulgaria was analyzed by physicochemical methods, gas chromatography (GC), GC
      mass spectrometry (MS) (achiral and chiral phases), and olfactometry, and its
      antimicrobial activity was tested by using different strains of microorganisms.
      More than 40 constituents of the essential dill oil, obtained from seeds stored
      for more than 35 years, could be identified as essential volatiles, responsible
      for the pleasant fresh (D-limonene) and spicy (D-carvone) odor of a high quality.
      As aroma impact compounds, D-carvone (50.1%) and D-limonene (44.1%) were found.
      Antimicrobial testings showed high activity of the essential A. graveolens oil
      against the mold Aspergillus niger and the yeasts Saccharomyces cerevisiae and
      Candida albicans.

PMID- 12797756
TI  - Influence of 1-methylcyclopropene on ripening, storage life, and volatile
      production by d'Anjou cv. pear fruit.
AB  - d'Anjou cv. pear fruit (Pyrus communis L.) exposed at harvest to 0, 0.42, 4.2, or
      42 micromol m(-)(3) 1-methylcyclopropene (1-MCP) for 12 h at 20 degrees C were
      stored at 1 degrees C for up to 8 months. After storage, half of the fruit was
      continuously exposed to ethylene (0.45 or 4-18 mmol m(-)(3)) for 7 days at 20
      degrees C. All fruit treated with 1-MCP had lower respiration and ethylene
      production compared to untreated controls. Fruit quality changes were delayed
      following 1-MCP treatment, as was development of superficial scald and peel
      yellowing. The duration of 1-MCP-induced responses was dependent on 1-MCP
      treatment concentration. When 1-MCP-treated fruit began to ripen, softening and
      production of volatile compounds proceeded similar to that of untreated fruit.
      Post-storage ethylene exposure did not consistently stimulate ripening of fruit
      previously treated with 1-MCP. Efficacy of ethylene treatment depended on 1-MCP
      concentration and storage duration.

PMID- 12797757
TI  - Structural and sensory characterization of compounds contributing to the bitter
      off-taste of carrots (Daucus carota L.) and carrot puree.
AB  - Sequential application of solvent extraction, gel permeation chromatography, and
      HPLC in combination with taste dilution analyses revealed that not a sole
      compound but a multiplicity of bitter tastants contribute to the bitter off-taste
      of cold-stored carrots and commercial carrot puree, respectively. Among these
      bitter compounds, 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin (6
      methoxymellein), 5-hydroxy-7-methoxy-2-methylchromone (eugenin), 2,4,5
      trimethoxybenzaldehyde (gazarin), (Z)-heptadeca-1,9-diene-4,6-diin-3,8-diol
      (falcarindiol), (Z)-heptadeca-1,9-diene-4,6-diin-3-ol (falcarinol), and (Z)-3
      acetoxy-heptadeca-1,9-diene-4,6-diin-8-ol (falcarindiol 3-acetate) could be
      identified on the basis of MS as well as 1D- and 2D-NMR experiments. Due to the
      low concentrations of <0.1 mg/kg and the high taste thresholds found for eugenin
      and gazarin, these compounds could be unequivocally excluded as important
      contributors to the bitter taste of carrots. Calculation of bitter activity
      values as the ratio of their concentration to their bitter detection threshold
      clearly demonstrated that neither in fresh and stored carrots nor in commercial
      carrot puree did 6-methoxymellein contribute to the bitter off-taste. In
      contrast, the concentrations of falcarindiol in stored carrots and, even more
      pronounced, in carrot puree were found to be 9- and 13-fold above its low bitter
      detection concentration of 0.04 mmol/kg, thus demonstrating that this acetylenic
      diol significantly contributes to the bitter taste of the carrot products
      investigated.

PMID- 12797758
TI  - Polyphenols from Honeybush tea (Cyclopia intermedia).
AB  - The fermented leaves and stems of Cyclopia intermedia are used to brew Honeybush
      tea, a herbal tea indigenous to South Africa. The plant is also used to
      manufacture a sweet herbal infusion used for restorative properties such as
      soothing coughs and alleviating bronchial complaints including tuberculosis,
      pneumonia, and catarrh. It is claimed to have a low tannin content and no
      caffeine and contains various antioxidants. Continued investigations into the
      phenolic content of the leaves and stems of C. intermedia yielded tyrosol and a
      methoxy analogue, 2-[4-[O-alpha-apiofuranosyl-(1' '-->6')-beta-d
      glucopyranosyloxy]phenyl]ethanol, 4-[O-alpha-apiofuranosyl-(1' '-->2')-beta-d
      glucopyranosyloxy]benzaldehyde, five glycosylated flavonols, two isoflavones,
      four flavanones, two isoflavones, and two flavones. Structure elucidation was
      done by NMR, CD, and MS methods. Because flavonoids are presumed to contribute
      significantly toward the scavenging effects of active oxygen species, our results
      indicate that the tentative claimed health-promoting properties may be attributed
      to the presence of these and other phenolics in C. intermedia.

PMID- 12797759
TI  - A new multistep Ca2+-induced cold gelation process for beta-lactoglobulin.
AB  - The objective of this study was to obtain beta-lactoglobulin (beta-lg) gels at
      very low protein concentrations using a new multistep Ca(2+)-induced cold
      gelation process. In the conventional cold gelation process, salt free beta-lg
      solutions were heated at neutral pH, cooled, and cross-linked by adding salts. In
      our new process, first, long linear beta-lg fibrils were formed at pH 2.
      Solutions of these fibrils were cooled, and subsequently, the pH was adjusted to
      7 or 8. Transmission electron microscopy studies showed that the long linear
      fibrils formed at pH 2 were stable when the pH was adjusted to 7 or 8. In the
      final step, the fibrils were cross-linked using CaCl(2). Using rheological
      measurements, the critical percolation concentration was determined. In the new
      multistep cold gelation process, the critical percolation concentration was an
      order of magnitude lower than in the conventional cold gelation method.

PMID- 12797760
TI  - Comparative analysis of different hemoglobins: autoxidation, reaction with
      peroxide, and lipid oxidation.
AB  - Beef hemoglobin (Hb) had lower levels of deoxyHb and autoxidized much slower as
      compared to trout Hb at pH 6.3. Chicken Hb autoxidized at a rate intermediate
      between beef and trout Hb. In the presence of hydrogen peroxide, metHb formed
      rapidly from trout Hb whereas beef Hb was essentially nonreactive with hydrogen
      peroxide. The autoxidation rate of perch Hb was more rapid than trout Hb despite
      the low deoxyHb content of perch Hb. Perch Hb was a better catalyst of lipid
      oxidation than trout Hb when added to washed cod muscle based on formation of
      lipid hydroperoxides and thiobarbituric acid reactive substances. These studies
      indicate that autoxidation rate does not always increase with increasing deoxyHb
      content. The role of heme crevice volume in heme protein autoxidation is
      discussed. Among other factors, these studies suggest that rates of lipid
      oxidation in various muscle foods may depend on the relative ability of
      hemoglobins from different animal species to promote lipid oxidation.

PMID- 12797761
TI  - Adhesive properties of corn zein formulations on glass surfaces.
AB  - Adhesive properties on glass of commercial zein and an inexpensive zein-lipid
      mixture isolated from dry-milled corn were investigated. A method was developed
      for uniformly preparing bonded glass panels and measuring the amount of pull
      required to separate the panels. The adhesive strength of commercial zein to
      glass was greater at 29% than at 52% relative humidity (RH). Bonded samples
      prepared from zein isolates were less sensitive to changes in RH. Bonds using
      commercial zein formulations containing plasticizer reached a maximum strength at
      10% poly(ethylene glycol) regardless of RH. Formulations that required the least
      amount of ethanol (35-42%) were obtained by adjusting its pH to 3 or 10 with a
      volatile acid or base. These formulations completely bonded to the glass panels
      at low sample concentrations as estimated by 100% cohesive failure and exhibited
      lower Young's Modulus values than most of the other bonding materials tested.
      Samples bonded with a polyvinyl acetate emulsion adhesive were not as strong as
      the zein-bonded samples and were sensitive to changes in RH.

PMID- 12797762
TI  - HPLC-DAD-MS/MS ESI characterization of unusual highly glycosylated acylated
      flavonoids from cauliflower (Brassica oleracea L. var. botrytis) agroindustrial
      byproducts.
AB  - In a recent program to investigate the possible use of vegetable handling and
      commercialization wastes and residues as a source of potentially bioactive
      extracts, we have studied cauliflower byproducts. A total of twenty-eight
      compounds were characterized by HPLC-DAD-MS, of these, twenty-two are produced
      naturally by the plant. The main compounds found were kaempferol 3-diglucoside-7
      glucoside and its combinations with different hydroxycinnamic acids. Moreover,
      some flavonoids with an unusual high grade of glycosylation have been isolated
      and tentatively identified for the first time. To our knowledge, the
      characterization of flavonoids with more than four sugars has not been previously
      reported. The new products isolated were tentatively identified as kaempferol 3
      diglucoside-7-diglucoside, kaempferol 3-triglucoside-7-diglucoside, kaempferol 3
      feruloyldiglucoside-7-diglucoside, kaempferol 3-sinapoyltriglucoside-7-glucoside,
      kaempferol 3-disinapoyltriglucoside-7-glucoside, kaempferol 3
      sinapoyltriglucoside-7-diglucoside and kaempferol 3-disinapoyltriglucoside-7
      diglucoside.

PMID- 12797763
TI  - Maillard reaction products inhibit oxidation of human low-density lipoproteins in
      vitro.
AB  - Dietary intake of antioxidants has been associated with a reduced risk of
      cardiovascular diseases, which is very likely caused by their capability of
      prevent oxidation of low-density lipoproteins (LDL). During food processing and
      storage, substances with antioxidative properties are formed by Maillard
      reactions. In this study, the activity of Maillard products to inhibit copper
      induced oxidation of human LDL in vitro was investigated. d-Glucose was heated
      with an equimolar amount of glycine, l-lysine, or l-arginine, for 1 h under
      reflux. The increase of the antioxidative activity (AOA) of the Maillard mixtures
      was highly significant compared to the control mixtures. Additionally, two
      defined Maillard products with amino reductone structure were tested. 3-Hydroxy-4
      (morpholino)-3-buten-2-one (1) and amino hexose reductone (2) showed a
      significant and dose dependent AOA. Compound 1 was about half as active as
      ascorbic acid, which served as positive control. Thus, it can be concluded that
      Maillard products, particularly those with amino reductone structure, have the
      strong potential to inhibit LDL oxidation.

PMID- 12797764
TI  - Influence on hazelnut oil administration on peroxidation status of erythrocytes
      and apolipoprotein B 100-containing lipoproteins in rabbits fed on a high
      cholesterol diet.
AB  - Hazelnut oil (HO) is rich in monounsaturated fatty acids (MUFA). The effect of a
      high cholesterol (HC) diet with and without HO on lipids and lipid peroxide
      levels in plasma, apolipoprotein B 100-containing lipoproteins (VLDL + LDL), and
      erythrocytes as well as hematological data was investigated in rabbits. A HC diet
      caused significant increases in lipid peroxide levels in plasma and apo B
      containing lipoproteins together with histopathological atherosclerotic findings
      in aorta. In addition, this diet resulted in hemolytic anemia associated with
      increased endogenous diene conjugate (DC) levels, but H(2)O(2)-induced
      malondialdehyde (MDA) levels remained unchanged in erythrocytes. HO
      supplementation reduced lipid peroxide levels in plasma and apolipoprotein B 100
      containing lipoproteins as well as aortic atherosclerotic lesions in rabbits fed
      an HC diet without any decreasing effect on lipid levels. In addition, HO was
      found to reduce hemolytic anemia together with significant decreases in DC and
      H(2)O(2)-induced MDA levels.

PMID- 12797767
TI  - Catalytic activity of supported Au nanoparticles deposited from block copolymer
      micelles.
AB  - Quasi-ordered, highly dispersed, gold nanoclusters of tightly controlled particle
      size were synthesized by dip-coating substrates with gold precursors encapsulated
      by block-copolymer micelles. By this method, gold particles (4.8 +/- 1.3 nm) were
      deposited on ITO-coated glass and shown to be catalytically active for electro
      oxidation of carbon monoxide. XPS confirmed the catalytically active particles
      were predominantly Au0; however, a large fraction existed as Au3+. Whereas bulk
      gold is inert, these results demonstrate that catalytically active Au
      nanoparticles can be derived from micelle encapsulation.

PMID- 12797766
TI  - Self-assembly combining two bioactive peptide-amphiphile molecules into
      nanofibers by electrostatic attraction.
AB  - We describe a new approach to peptide-amphiphile (PA) nanofiber preparation that
      allows PAs with different bioactive amino acid sequences to be combined into a
      single fiber. Oppositely charged PAs are synthesized separately and then mixed to
      produce gels of nanofiber networks at physiological pH. Transmission electron
      microscopy reveals the formation of fibers approximately 7 nm in diameter and
      several micrometers long in these dimeric systems. On the basis of NMR and
      microscopy, we suggest that these nanofibers are cylindrical micelles of mixed
      composition, formed due to electrostatic attraction between the oppositely
      charged PAs. This strategy for self-assembly may be useful in cell therapies that
      can be implemented without invasive surgery or in in vitro tissue engineering.

PMID- 12797768
TI  - Amphicatalytic polymerization: synthesis of stereomultiblock poly(methyl
      methacrylate) with diastereospecific ion pairs.
AB  - Diastereospecific ion pairs consisting of isospecific transition-metal cations
      and syndiospecific main-group anions promote what is termed amphicatalytic
      polymerization of MMA, producing PMMA with isotactic-b-syndiotactic
      stereomultiblock microstructures.

PMID- 12797769
TI  - 100% encapsulation of a hydrogen molecule into an open-cage fullerene derivative
      and gas-phase generation of H2@C60.
AB  - By applying high-pressure H2 to a new fullerene derivative, C63NO2SPh2Py (1),
      having a 13-membered-ring orifice, 100% incorporation of a H2 molecule into the
      fullerene cage has been achieved for the first time. This result substantiates
      the theoretical calculations indicating that the energy barrier required for H2
      insertion through an orifice in 1 is considerably lower than that for the
      previously reported derivative with the largest orifice among open-cage
      fullerenes synthesized thus far. Upon matrix-assisted laser desorption/ionization
      mass spectroscopy, the removal of organic addends from the fullerene derivative 1
      encapsulating H2 and restoration of the pristine C60 cage, which retains
      approximately one-third of incorporated H2, have been observed.

PMID- 12797770
TI  - Multivalency and the mode of action of bacterial sialidases.
AB  - Although complex modular proteins are encountered frequently in a variety of
      biological systems, their occurrence in biocatalysis has not been widely
      appreciated. Here, we describe that bacterial sialidases, which have both a
      catalytic and carbohydrate-binding domain, can hydrolyze polyvalent substrates
      with much greater catalytic efficiency than their monovalent counterparts. The
      enhancement of catalytic efficiency was due to a much smaller Michaelis constant
      and rationalized by a model in which the catalytic and lectin domains interact
      simultaneously with the polyvalent substrate, leading to an enhancement of
      affinity. Inhibition studies have shown that galactosides released by the action
      of the sialidase can act as the ligand for the lectin domain. This knowledge has
      been exploited in the design of a potent polyvalent inhibitor of the sialidase of
      Vibrio cholerae, which displayed exquisite selectivities for sialidases that have
      a lectin domain.

PMID- 12797771
TI  - Gold electrodes wired for coupling with the deeply buried active site of
      Arthrobacter globiformis amine oxidase.
AB  - Diethylaniline-terminated oligo(phenyl-ethynyl)-thiol (DEA-OPE-SH) wires on Au
      bead electrodes facilitate electron tunneling to and from the deeply buried
      topaquinone (TPQ) cofactor in Arthrobacter globiformis amine oxidase (AGAO).
      Reversible cyclic voltammograms were observed when AGAO was adsorbed onto this
      DEA-OPE-SAu surface: the 2e-/2H+ reduction potential is -140 mV versus SCE.

PMID- 12797772
TI  - Regio- and enantiospecific rhodium-catalyzed arylation of unsymmetrical
      fluorinated acyclic allylic carbonates: inversion of absolute configuration.
AB  - The transition metal-catalyzed allylic substitution with unstabilized carbon
      nucleophiles represents an important cross-coupling reaction for the construction
      of ternary carbon stereogenic centers. We have developed a new regio- and
      enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical
      chiral nonracemic allylic alcohol derivatives with aryl zinc bromides. This study
      demonstrates that the hydrotris(pyrazolyl)borate rhodium catalyst and zinc(II)
      halide salt are crucial for efficiency, while the addition of lithium bromide to
      the catalyst is necessary for obtaining optimal regiospecificity. The
      stereochemical course of this reaction was established through the synthesis of
      (S)-ibuprofen, which demonstrated that the alkylation proceeds with net inversion
      of absolute configuration consistent with direct addition of the nucleophile to
      the metal center followed by reductive elimination.

PMID- 12797773
TI  - Chemoenzymatic route to macrocyclic hybrid peptide/polyketide-like molecules.
AB  - Hybrid peptide-polyketides are a class of medically and biologically important
      natural products characterized by stereochemical and functional diversity. In
      their biosynthesis, hybrids are often macrocyclized to achieve rigid structures
      that populate bioactive conformations. We herein present a chemoenzymatic
      strategy to access the stereochemical and functional diversity found in
      macrocyclic hybrid natural products in a manner amenable to efficient library
      synthesis. Our method makes use of small building blocks in the form of Fmoc
      protected epsilon-amino acids containing embedded polyketide functionality. The
      building block approach allows for combinatorial synthesis of linear molecules
      that can be activated as soluble thioesters or tethered to a solid-phase resin.
      We demonstrate that these linear molecules are substrates for macrocyclization by
      a tolerant catalyst, TycC TE, derived from a nonribosomal peptide synthetase. The
      method should allow for access to diverse structures with hybrid peptide
      polyketide character that can be screened for improved or novel activities.

PMID- 12797774
TI  - Transfer-printing of highly aligned DNA nanowires.
AB  - We developed a simple method of reproducibly creating highly aligned DNA
      nanowires without any surface modifications or special equipment. Stretched DNA
      molecules initially present on the PDMS sheet were transferred onto another
      surface using transfer-printing (TP). Fluorescent microscopic and atomic force
      microscopic images revealed that many DNA molecules were highly aligned on
      surfaces after TP. Furthermore, it was also possible to realize the two
      dimensional assembly of DNA nanowires by repeating TP.

PMID- 12797775
TI  - A new strategy for improved nicotine vaccines using conformationally constrained
      haptens.
AB  - Constrained nicotine analogues were synthesized and coupled to the carrier
      protein KLH. The immunogenic effects were compared to those using our previously
      designed flexible nicotine hapten. Immunization of mice with the constrained
      hapten conjugates resulted in highly increased antibody titers and affinity for
      nicotine.

PMID- 12797776
TI  - Efficient electroluminescence from a new terbium complex.
AB  - Although lanthanide complexes have distinct advantages for use as light-emitting
      materials, such as sharp emission bands and 100% quantum efficiency
      theoretically, their performance was far below what is expected. A new terbium
      complex was designed and synthesized. Devices using it as an emitter present
      satisfactory performance, with the highest brightness of 12 000 cd/m2 and power
      efficiency of 11.3 lm/W, which is nearly 1 order of magnitude higher than what
      was reported previously. Comparison with analogous complexes indicated that this
      result originated from the terbium complex's well-balanced charge-transport
      properties.

PMID- 12797777
TI  - Bioconjugated nanoparticles for DNA protection from cleavage.
AB  - We have developed a novel method to protect DNA from cleavage using bioconjugated
      nanoparticles. Positively charged amino-modified silica nanoparticles have been
      directly prepared using water-in-oil microemulsion. Plasmid DNA can be easily
      enriched onto the positively charged nanoparticle surface, and the DNA strands
      are well protected from enzymatic cleavage. When incubated with nuclease enzyme
      for enzymatic cleavage, free plasmid DNA strands are completely cleaved, while
      those on the nanoparticle surfaces are intact. Our results clearly demonstrate
      unique properties of nanomaterials when combined with biomolecules. Our simple
      bionanotechnology will be highly useful in DNA separation, manipulation, and
      detection, and possibly in genetic engineering and gene therapy, as plasmid DNA
      can be protected in cellular environments without any change in its property.

PMID- 12797778
TI  - A metal-centered hydrophobic pocket recognizing pyridine over piperidine.
AB  - Two external spaces of an inorganic tennis ball are a novel type of metal
      centered hydrophobic pocket where two hydrophobic trans-(+/-)-1,2
      diaminocyclohexane groups stand perpendicularly to and around the metal
      coordination plane. The space recognizes pyridine over piperidine, and a novel
      supramolecule was obtained using such pyridine recognition properties.

PMID- 12797779
TI  - Origin of the regiochemistry of propene insertion at octahedral column 4
      polymerization catalysts: design or serendipity?
AB  - The new octahedral column 4 catalysts bearing phenoxy-amine or phenoxy-imine
      ligands have opposite regioselectivities in propene polymerization. In this
      Communication, we report on a QM/MM investigation indicating that one of the key
      factors controlling the regiochemistry of propene insertion is the nature of the
      N atoms: steric and electronic effects related to the different hybridization
      synergically favor 1,2 or 2,1 insertion when the said N's are respectively of
      amine or imine type.

PMID- 12797780
TI  - Light-induced modulation of self-assembly on spiropyran-capped gold
      nanoparticles: a potential system for the controlled release of amino acid
      derivatives.
AB  - A photoswitchable double-shell structure on Au nanoparticles, consisting of
      photochromic spiropyran as the first shell, which regulates the assembly and
      release of an outer shell of amino acid derivatives upon irradiation, is being
      reported for the first time. The light-regulated changes in the topographic
      properties of spiropyran-capped Au nanoparticles (i.e., interconversion between
      the zwitterionic and neutral forms) are exploited for the assembly and release of
      amino acid-based therapeutic agents such as l-DOPA.

PMID- 12797781
TI  - Accurate ionization potentials for UO and UO2: a rigorous test of relativistic
      quantum chemistry calculations.
AB  - Accurate ionization potential (IP) measurements provide essential thermodynamic
      information and benchmark data that can be used to evaluate the validity of
      electronic structure models. Calculations of the first IP of UO2 using
      relativistic methods consistently predict values that are approximately 0.7 eV
      higher than the accepted experimental value. The present measurements validate
      the theoretical calculations and show that the previous determinations
      corresponded to the ionization of thermally excited molecules. Similarly, new
      measurements of the IP for UO show that the currently accepted value is too low
      by 0.4 eV.

PMID- 12797782
TI  - Hybrid QM/MM study of thio effects in transphosphorylation reactions.
AB  - Results of a series of hybrid quantum mechanical/molecular mechanical (QM/MM)
      activated dynamics simulations of thio effects in the transphosphorylation
      (methanolysis) of a 2'-ribose, 5'-methyl phosphate-diester under basic conditions
      are presented. Single and double substitutions in the nonbridging oxygen
      positions exhibit thio effects in accord with experimental data and show the
      existence of a stable intermediate. Thio substitution at the 2' and 5' positions
      resulted in reactions having a single transition state with increased and
      decreased free energy barriers, respectively, relative to the unsubstituted
      reaction. In all of the reactions except for the 5' substitution, the rate
      limiting step corresponds to exocyclic cleavage. In the 5' substitution reaction,
      the rate-limiting step corresponds to endocyclic cleavage and shows a
      considerable reverse thio effect, in accord with experimental observations of
      phosphates with enhanced leaving groups. Thio substitution at the 3' position
      results in a mild reverse thio effect that arises from electronic stabilization
      of the dianionic transition state. The results presented here provide an
      important step toward the development and application of new hybrid QM/MM methods
      that, combined with experiment, may provide a detailed picture of the molecular
      mechanisms of RNA catalysis.

PMID- 12797783
TI  - Protein semi-synthesis in living cells.
AB  - Incorporation of chemical probes into proteins is a powerful way to elucidate
      biological processes and to engineer novel function. Here we describe an approach
      that allows ligation of synthetic molecules to target proteins in an
      intracellular environment. A cellular protein is genetically tagged with one-half
      of a split intein. The complementary half is linked in vitro to the synthetic
      probe, and this fusion is delivered into cells using a transduction peptide.
      Association of the intein halves in the cytosol triggers protein trans-splicing,
      resulting in the ligation of the probe to the target protein through a peptide
      bond. This process is specific and applicable to cytosolic and integral membrane
      proteins. The technology should allow cellular proteins to be elaborated with a
      variety of abiotic probes.

PMID- 12797784
TI  - Direct detection of potassium cations bound to G-quadruplex structures by solid
      state 39K NMR at 19.6 T.
AB  - We report solid-state 39K NMR detection of the K+ ions bound to three G
      quadruplex structures formed by self-assembly of 5'-tert-butyl-dimethylsilyl
      2',3'-O-isopropylidene guanosine, guanosine, and guanosine 5'-monophosphate. The
      39K NMR spectra clearly show different spectral signatures for K+ ions inside the
      G-quadruplex channel and for K+ ions bound to the phosphate groups. Solid-state
      39K NMR spectra for hydrated K salts of adenosine 2'-monophosphate and adenosine
      5'-diphosphate are also reported.

PMID- 12797786
TI  - Helix-turn-helix motifs in unsolvated peptides.
AB  - The conformations of unsolvated Ac-A14KG3A14K + 2H+ (Ac = acetyl, A = alanine, K
      = lysine, G = glycine) have been examined by ion mobility measurements and
      molecular dynamics simulations. This peptide was designed as a model helix-turn
      helix motif. It was found to adopt three distinct geometries which were assigned
      to an extended helical conformation which is only stable at low temperatures
      (<230 K), a relatively high energy but metastable structure with exchanged
      lysines, and a coiled-coil. The coiled coil (which consists of an antiparallel
      arrangement of two helical alanine sections linked by a flexible glycine loop) is
      the dominant conformation. For temperatures >350 K, the experimental results
      indicate the helices uncouple and the loop randomizes. From equilibrium constants
      determined for this helix coupling right arrow over left arrow uncoupling
      transition, we found DeltaH degrees = -45 kJ mol-1 and DeltaS degrees = 114 J K-1
      mol-1. -DeltaH degrees is essentially the enthalpy change for docking the two
      helices together while DeltaS degrees is essentially the entropy change for
      freeing up the glycine loop.

PMID- 12797785
TI  - Mechanisms of allene stereoinversion by imidozirconium complexes.
AB  - The zirconium-mediated stereoinversion of allenes has been investigated by
      studying the stereochemical behavior of metallacycles derived from [2 + 2]
      cycloaddition of enantioenriched allenes with chiral and achiral imidozirconocene
      complexes. Relative rates of metallacycle racemization were measured by circular
      dichroism, and intermediates in the selective stereoinversion of diphenylallene
      with a chiral imidozirconium complex were observed by NMR spectroscopy.
      Metallacycles derived from dialkylallenes are proposed to racemize via reversible
      beta-hydride elimination. Stereoinversion of diarylallene-derived metallacycles
      proceeds much more slowly and is thought to proceed through an eta4
      azatrimethylenemethane transition state.

PMID- 12797787
TI  - Diamond-type lipid cubic phase with large water channels.
AB  - This paper describes a diamond cubic phase with large water channels and
      determines the temperature dependence of the bilayer thickness in the cubic
      monoolein/octylglucoside/water system based on time-resolved synchrotron X-ray
      diffraction data. The X-ray diffraction study established a diamond-type lipid
      cubic phase with large water channels (Dlarge), which has not been previously
      reported. It is a distinct phase, different from the diamond cubic phase with
      normal water channels (Dnormal). The larger channels might allow an enhanced
      entrapment efficiency of biomolecules in lipid cubic phases. The X-ray
      diffraction patterns recorded during a thermal scan showed a cubic-cubic
      structural transition from Dlarge to Dnormal. The obtained cubic phases displayed
      much larger lattice spacings as compared to those of pure monoolein at full
      hydration.

PMID- 12797788
TI  - Linking atomistic and mesoscale simulations of water-soluble polymers.
AB  - A link between molecular and mesoscopic simulations for water-soluble polymers is
      made using the potential of mean force (PMF) method. Mesoscale parameters are
      adjusted to match selected thermodynamic quantities such as the monomer second
      virial coefficient or the limiting slope of the monomer adsorption isotherm,
      which are computed directly from atomistic PMFs. The method is illustrated by
      computing the bulk and surface interaction parameters (chi parameters in self
      consistent field theory) for the adsorption of ethylene oxide (EO) and propylene
      oxide (PO) polymers from aqueous solution onto silica.

PMID- 12797789
TI  - Observation of quantum coherence for recurrence motion of exciton in anthracene
      dimers in solution.
AB  - The quantum beat signal associated with recurrence motion of exciton was observed
      for two types of anthracene dimers connected through a phenyl ring, on
      femtosecond fluorescence anisotropy decay. The time periods of oscillation were
      0.3-0.9 ps, which correspond to exciton interactions of 30-50 cm-1, and the
      damping time constants (dephasing time) were 0.7-1.0 ps. The results show that
      the coherent aspect in photochemical processes is observable even in solution at
      room temperature, if one employs dimers of rigid structures.

PMID- 12797790
TI  - Diastereoselective photochromism of a bisbenzothienylethene governed by steric as
      well as electronic interactions.
AB  - Introduction of an asymmetric center to C-2 of one of the benzothiophene rings of
      bisbenzothienylperfluorocyclopentene results in a highly diastereoselective
      photochromic system. The stereogenic center bears a hydrogen atom, a methyl
      group, and a methoxymethoxy group. The steric as well as the electronic
      repulsions gave an 87-88% diastereomer excess in various solvents at room
      temperature with 80-85% conversion to the colored form. The enantioselective
      synthesis was also carried out. Upon photoirradiation in hexane, a change in
      optical rotation at 820 nm, where neither the open form nor the colored form
      absorbs light, was observed repeatedly.

PMID- 12797791
TI  - Spectroscopic evidence for hydrogen diffusion through a several-nanometers-thick
      titanium carbonitride layer on silicon.
AB  - Multiple internal reflection Fourier transform infrared spectroscopy, together
      with other analytical techniques, was used to follow the diffusion of atomic
      hydrogen through a 10-nm-thick titanium carbonitride layer deposited onto a
      Si(100)-2x1 surface from tetrakis(dimethylamino)titanium as a chemical vapor
      deposition precursor. The recombinative desorption of hydrogen from the TiCN/Si
      interface was shown to coincide with the temperature range where most Ti-based
      diffusion barriers break down.

PMID- 12797792
TI  - Catalytic enantioselective hydroboration of cyclopropenes.
AB  - 2,2-Disubstituted cyclopropyl boronates have been synthesized with high degrees
      of diastereo- and enantioselectivity via the rhodium-catalyzed asymmetric
      hydroboration of 3,3-disubstituted cyclopropenes. A strong directing effect of
      ester and alkoxymethyl substituents has been demonstrated. The directing effect
      was found to be necessary in achieving high degrees of enantiomeric induction.
      Selected cyclopropylboronic derivatives were successfully employed in the Suzuki
      cross-coupling reaction to produce the corresponding optically active aryl- and
      vinylcyclopropanes in good yields.

PMID- 12797793
TI  - A strategy for the NMR characterization of type II copper(II) proteins: the case
      of the copper trafficking protein CopC from Pseudomonas Syringae.
AB  - CopC from Pseudomonas syringae was found to be a protein capable of binding both
      Cu(I) and Cu(II) at two different sites. The solution structure of the apo
      protein is available, and structural information has been obtained on the Cu(I)
      bound form. We attempt here to set the limits for the determination of the
      solution structure of a Cu(II) protein, such as the Cu(II) bound form of CopC, in
      which the Cu(II) ion takes a type II coordination. The electron relaxation time
      is estimated from NMRD measurements to be 3 ns which leads to a correlation time
      for the nuclear spin-electron spin dipolar interaction of 2 ns. This information
      allowed us to tailor the NMR experiments and to fully exploit purely
      heteronuclear spectroscopy to assign as many signals as possible. In this way, 37
      (13)C and 11 (15)N signals that completely escape detection with conventional
      approaches were assigned. Paramagnetic based structural constraints were obtained
      by measuring paramagnetic longitudinal relaxation enhancements (rho(para)) which
      allowed us to precisely locate the copper ion within the protein frame.
      Pseudocontact shifts (pcs's) were also used as constraints for 83 (1)H and 18
      (13)C nuclei. With them, together with other standard structural constraints, a
      structure is obtained (and submitted to PDB) where information is only missing in
      a sphere with a 6 A radius from the copper ion. If we borrow information from
      EXAFS data, which show evidence of two copper coordinated histidines, then His 1
      and His 91 are unambiguously identified as copper ligands. EXAFS data indicate
      two more light donor atoms (O/N) which could be from Asp 27 and Glu 89, whereas
      the NMRD data indicate the presence of a semicoordinated water molecule at 2.8 A
      (Cu-O distance) roughly orthogonal to the plane identified by the other four
      ligands. This represents the most extensively characterized structure of a type
      II Cu(II) protein obtained employing the most advanced NMR methods and with the
      aid of EXAFS data. The knowledge of the location of the Cu(II) in the protein is
      important for the copper transfer mechanism.

PMID- 12797794
TI  - FTIR detection of protonation/deprotonation of key carboxyl side chains caused by
      redox change of the Cu(A)-heme a moiety and ligand dissociation from the heme a3
      Cu(B) center of bovine heart cytochrome c oxidase.
AB  - FTIR spectral changes of bovine cytochrome c oxidase (CcO) upon ligand
      dissociation from heme a(3)() and redox change of the Cu(A)-heme a moiety
      (Cu(A)Fe(a)()) were investigated. In a photosteady state under CW laser
      illumination at 590 nm to carbonmonoxy CcO (CcO-CO), the C-O stretching bands due
      to Fe(a3)()(2+)CO and Cu(B)(1+)CO were identified at 1963 and 2063 cm(-)(1),
      respectively, for the fully reduced (FR) state
      [(Cu(A)Fe(a)())(3+)Fe(a3)()(2+)Cu(B)(1+)] and at 1965 and 2061 cm(-)(1) for the
      mixed valence (MV) state [(Cu(A)Fe(a)())(5+)Fe(a3)()(2+)Cu(B)(1+)] in H(2)O as
      well as in D(2)O. For the MV state, however, another band due to Cu(B)(1+)CO was
      found at 2040 cm(-)(1), which was distinct from the alpha/beta conformers in the
      spectral behaviors, and therefore was assigned to the
      (Cu(A)Fe(a)())(4+)Fe(a3)()(3+)Cu(B)(1+)CO generated by back electron transfer.
      The FR-minus-oxidized difference spectrum in the carboxyl stretching region
      provided two negative bands at 1749 and 1737 cm(-)(1) in H(2)O, which were
      apparently merged into a single band with a band center at 1741 cm(-)(1) in
      D(2)O. Comparison of these spectra with those of bacterial enzymes suggests that
      the 1749 and 1737 cm(-)(1) bands are due to COOH groups of Glu242 and Asp51,
      respectively. A similar difference spectrum of the carboxyl stretching region was
      also obtained between (Cu(A)Fe(a)())(3+)Fe(a3)()(2+)Cu(B)(1+)CO and
      (Cu(A)Fe(a)())(5+)Fe(a3)()(2+)Cu(B)(1+)CO. The results indicate that an oxidation
      state of the (Cu(A)Fe(a)()) moiety determines the carboxyl stretching spectra. On
      the other hand, CO-dissociated minus CO-bound difference spectra in the FR state
      gave rise to a positive and a negative peaks at 1749 and 1741 cm(-)(1),
      respectively, in H(2)O, but mainly a negative peak at 1735 cm(-)(1) in D(2)O. It
      was confirmed that the absence of a positive peak is not caused by slow
      deuteration of protein. The corresponding difference spectrum in the MV state
      showed a significantly weaker positive peak at 1749 cm(-)(1) and an intense
      negative peak at 1741 cm(-)(1) (1737 cm(-)(1) in D(2)O). The spectral difference
      between the FR and MV states is explained satisfactorily by the spectral change
      induced by the electron back flow upon CO dissociation as described above. Thus,
      the changes of carboxyl stretching bands induced both by oxidation of
      (Cu(A)Fe(a)()) and dissociation of CO appear at similar frequencies (
      approximately 1749 cm(-)(1)) but are ascribed to different carboxyl side chains.

PMID- 12797795
TI  - Hydration changes accompanying nucleic acid intercalation reactions:volumetric
      characterizations.
AB  - We use high precision ultrasonic velocimetric and densimetric techniques to
      determine at 25 degrees C the changes in volume, deltaV, and adiabatic
      compressibility, deltaK(S), that accompany the binding of ethidium to the
      poly(rA)poly(rU), poly(dAdT)poly(dAdT), poly(dGdC)poly(dGdC), and
      poly(dIdC)poly(dIdC) duplexes, as well as to the poly(rU)poly(rA)poly(rU)
      triplex. The binding of ethidium to each of the duplexes and the triplex is
      accompanied by negative changes in volume, deltaV, and adiabatic compressibility,
      deltaK(S). We discuss the basis for relating macroscopic and microscopic
      properties, particularly, emphasizing how measured changes in volume and
      compressibility can be quantitatively interpreted in terms of the differential
      hydration properties of DNA and RNA structures in their ligand-free and ligand
      bound states. We also estimate the entropic cost of intercalation-induced changes
      in hydration of each of the nucleic acid structures and the drug. In general, our
      results emphasize the vital role of hydration in modulating the energetics of
      drug-DNA binding, while also underscoring the fact that hydration must be
      carefully taken into account in analysis and prediction of the energetics of
      nucleic acid recognition.

PMID- 12797796
TI  - Structure determination of a peptide model of the repeated helical domain in
      Samia cynthia ricini silk fibroin before spinning by a combination of advanced
      solid-state NMR methods.
AB  - Fibrous proteins unlike globular proteins, contain repetitive amino acid
      sequences, giving rise to very regular secondary protein structures. Silk fibroin
      from a wild silkworm, Samia cynthia ricini, consists of about 100 repeats of
      alternating polyalanine (poly-Ala) regions of 12-13 residues in length and Gly
      rich regions. In this paper, the precise structure of the model peptide,
      GGAGGGYGGDGG(A)(12)GGAGDGYGAG, which is a typical repeated sequence of the silk
      fibroin, was determined using a combination of three kinds of solid-state NMR
      studies; a quantitative use of (13)C CP/MAS NMR chemical shift with conformation
      dependent (13)C chemical shift contour plots, 2D spin diffusion (13)C solid-state
      NMR under off magic angle spinning and rotational echo double resonance. The
      structure of the model peptide corresponding to the silk fibroin structure before
      spinning was determined. The torsion angles of the central Ala residue, Ala(19),
      in the poly-Ala region were determined to be (phi, psi) = (-59 degrees, -48
      degrees ) which are values typically associated with alpha-helical structures.
      However, the torsion angles of the Gly(25) residue adjacent to the C-terminal
      side of the poly-Ala chain were determined to be (phi, psi) = (-66 degrees, -22
      degrees ) and those of Gly(12) and Ala(13) residues at the N-terminal of the poly
      Ala chain to be (phi, psi) = (-70 degrees, -30 degrees ). In addition, REDOR
      experiments indicate that the torsion angles of the two C-terminal Ala residues,
      Ala(23) and Ala(24), are (phi, psi) = (-66 degrees, -22 degrees ) and those of N
      terminal two Ala residues, Ala(13) and Ala(14) are (phi, psi) = (-70 degrees, -30
      degrees ). Thus, the local structure of N-terminal and C-terminal residues, and
      also the neighboring residues of alpha-helical poly-Ala chain in the model
      peptide is a more strongly wound structure than found in typical alpha-helix
      structures.

PMID- 12797797
TI  - Formation and characterization of protein-protein complexes in vacuo.
AB  - Gas-phase reactions between multiply charged positive and negative protein ions
      are carried out in a quadrupole ion trap mass spectrometer. The ions react with
      one another by proton transfer and complex formation. Proton transfer products
      and complexes are formed via competitive processes in single ion/ion encounters.
      The relative contributions of proton transfer versus complex formation are
      dependent upon the charges of the ions as well as other characteristics of the
      ions yet to be clearly delineated. No fragmentation of covalent bonds of the
      protein reactants is observed. A model that considers the trajectories associated
      with ion/ion interactions appears to hold the most promise in accounting for the
      results. The formation of bound ion/ion orbits appears to play an important role
      in determining overall reaction kinetics as well as the distribution of ion/ion
      reaction products. Tandem mass spectrometry is used to compare protein complexes
      formed in the gas-phase with those formed initially in solution and subsequently
      liberated by electrospray; it is shown that both forms of complex dissociate
      similarly, but the complexes formed in the gas phase can retain a "memory" of
      their method of formation.

PMID- 12797798
TI  - Construction of giant dendrimers using a tripodal building block.
AB  - Giant pentane-soluble organo-silicon dendrimers have been synthesized using a
      triallylphenol brick according to a new divergent construction that uses a
      hydrosilylation-nucleophilic substitution sequence up to the ninth generation
      (G(9)). All the reactions were monitored by (1)H, (13)C, and (29)Si NMR until
      G(9), indicating that they were clean at the NMR accuracy until this last
      generation. MALDI TOF mass spectra were recorded for G(1) to G(4) and show the
      nature and amounts of defects that are intrinsic to the divergent construction.
      This technique and SEC (recorded up to G(5)) confirm the monodispersity (1.00 to
      1.02) from G(1) to G(5). HRTEM and AFM images recorded for the high generations
      disclose the expected smooth dendrimer size progression and the globular shape.
      At G(9), the theoretical number of termini (TNT) is 177 407 branches
      (abbreviation: G(9)-177 047). It is estimated that more than 10(5) terminal
      branches are actually present in the G(9) dendrimer, far beyond the De Gennes
      "dense-packing" limit (6000 branches), and it is believed that the branch termini
      turn inside the dendrimer toward the core. This is corroborated by lower reaction
      rates and yields for the highest generation numbers presumably due to
      intradendritic reactions. It is probable that the dendritic construction is
      limited by the density of branches inside the dendrimer, i.e., far beyond the
      dense-packing limit.

PMID- 12797799
TI  - A unique autocatalytic process and evidence for a concerted-stepwise mechanism
      transition in the dissociative electron-transfer reduction of aryl thiocyanates.
AB  - Electrochemical reduction of p-methyl-, p-methoxy-, and 3,5-dinitrophenyl
      thiocyanates as well as p-methyl- and p-methoxyphenyl disulfides was investigated
      in acetonitrile at an inert electrode. This series of compounds reveals a
      striking change in the reductive cleavage mechanism of the S-CN bond in
      thiocyanates as a function of the substituent on the aryl ring of the aryl
      thiocyanate. With nitro substituents, a stepwise mechanism, with an anion radical
      as the intermediate, takes place. When electron-donating groups (methyl and
      methoxy) are present, voltammetric as well as convolution analyses provide clear
      evidence for a transition between the concerted and stepwise mechanisms based on
      the magnitude of the transfer coefficient alpha. Moreover, a very interesting
      autocatalytic process is involved during the electrochemical reduction of these
      compounds. This process involves a nucleophilic substitution reaction on the
      initial aryl thiocyanate by the electrochemically generated arenethiolate ion. As
      a result of this unusual process, the electrochemical characteristics (peak
      potential and peak width) of the investigated series are concentration dependent.

PMID- 12797800
TI  - The first azacyclopentenyl carbinyl radical isomerizations (ACCRI): independent
      use of steric and electronic (polarization) effects as gating elements.
AB  - The first examples of the azacyclopentenyl carbinyl radical isomerization are
      described within a series of enantiomerically enriched 2-substituted indolines, a
      substructure found extensively in both heterocyclic and natural product
      chemistry. The isomerization was identified by the varying loss of enantiomeric
      enrichment (ee) of imines during aryl radical cyclizations to azomethine
      nitrogen. Independent modification of the steric and electronic nature of the
      ring substituents revealed the full spectrum of sensitivity to these variables
      and ultimately defined the use of these effects as gating elements. An example is
      also given in which a 1,4-amino group transfer is effected via the isomerization
      mechanism. Analogies are drawn between the title isomerization and the
      azacyclopropyl carbinyl radical isomerization that has been studied in both
      chemical and biological contexts.

PMID- 12797801
TI  - Triplex selective 2-(2-naphthyl)quinoline compounds: origins of affinity and new
      design principles.
AB  - A novel competition dialysis assay was used to investigate the structural
      selectivity of a series of substituted 2-(2-naphthyl)quinoline compounds designed
      to target triplex DNA. The interaction of 14 compounds with 13 different nucleic
      acid sequences and structures was studied. A striking selectivity for the triplex
      structure poly dA:[poly dT](2) was found for the majority of compounds studied.
      Quantitative analysis of the competition dialysis binding data using newly
      developed metrics revealed that these compounds are among the most selective
      triplex-binding agents synthesized to date. A quantitative structure-affinity
      relationship (QSAR) was derived using triplex binding data for all 14 compounds
      used in these studies. The QSAR revealed that the primary favorable determinant
      of triplex binding free energy is the solvent accessible surface area. Triplex
      binding affinity is negatively correlated with compound electron affinity and the
      number of hydrogen bond donors. The QSAR provides guidelines for the design of
      improved triplex-binding agents.

PMID- 12797802
TI  - Synthesis of [L-Ala-1]RA-VII, [D-Ala-2]RA-VII, and [D-Ala-4]RA-VII by
      epimerization of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants,
      through oxazoles.
AB  - Three epimers of a natural cyclic hexapeptide RA-VII were prepared via formation
      of oxazoles from thioamides or thioimidates of RA-VII followed by hydrolysis.
      They are the epimers at l-Ala-1, d-Ala-2, and d-Ala-4, respectively. The one
      having l-Ala-1 adopted trans-cis-trans-trans-trans-trans (t-c-t-t-t-t) amide
      configurations in the crystal, a type-VI beta-turn for residues 1-4 stabilized by
      one intramolecular hydrogen bond between Ala-4 NH and l-Ala-1 C = O, and in
      CDCl(3) existed as a mixture of six conformers, of which the major conformer was
      very similar to that in the crystal, but quite different from that of RA-VII in
      solution. The second epimer, having d-Ala-2 had in the crystalline state t-t-t-t
      c-t amide configurations, a gamma-turn at Tyr-3 stabilized by two intramolecular
      hydrogen bonds between d-Ala-2 NH and Ala-4 C = O and between Ala-4 NH and d-Ala
      2 C = O, and existed in CDCl(3) as a single conformer, the structure of which was
      very similar to its crystal structure, and to the crystal structure of peptide 25
      except for the backbone and the side chains at residues 1 and 2. The third
      epimer, having d-Ala-4 had t-c-t-t-c-t amide configurations in the crystal, a
      type-VI beta-turn for residues 1-4 as observed in the first epimer, and in
      CDCl(3) existed in three conformers, of which the major one was similar to that
      in the crystal but different from that of RA-VII in solution. The three epimers
      showed very weak cytotoxicity on P-388 leukemia cells, which may be because of
      their conformational differences from the active conformation of RA-VII.

PMID- 12797803
TI  - Michael addition of stannyl ketone enolate to alpha,beta-unsaturated esters
      catalyzed by tetrabutylammonium bromide and an ab initio theoretical study of the
      reaction course.
AB  - Michael addition of stannyl ketone enolates to alpha,beta-unsaturated esters was
      accomplished in the presence of a catalytic amount of tetrabutylammonium bromide
      (Bu(4)NBr). Other typical systems using lithium enolate or silyl enolate with
      catalysts (TiCl(4) or Bu(4)NF) failed to give the desired products. The bromide
      anion from Bu(4)NBr coordinates to the tin center in enolate to accelerate the
      conjugate addition where a five-coordinated tin species was generated. The
      coordination of the bromide anion significantly raises the HOMO level of tin
      enolate and enhances its nucleophilicity. The conjugate addition provides the
      intermediate Michael adduct, which has an ester enolate moiety, and the adduct
      immediately transforms to alpha-stannyl gamma-ketoester by keto-enol
      tautomerization. This step contributes to the stabilization of the product system
      and leads to a thermodynamically favorable reaction course. An ab initio
      calculation reveals that the activation energy in the reaction using the bromide
      anion is lower than that of the reaction without using it. The transition state
      in either reaction course has a linear structure, not a cyclic one. This system
      can be applied to a variety of tin enolates and alpha,beta-unsaturated carbonyls
      involving enoates, enones, and unsaturated amides.

PMID- 12797804
TI  - Single side strapping: a new approach to fine tuning the anion recognition
      properties of calix[4]pyrroles.
AB  - Three calix[4]pyrroles bearing m-orcinol-derived diether straps of different
      lengths on one side of the tetrapyrrolic core have been synthesized and
      characterized. Structural information for an analogous diester bridged strapped
      system reported previously (Yoon, D. W.; Hwang, H.; Lee, C. H. Angew. Chem., Int.
      Ed. Engl. 2002, 41, 1757-1759) is also provided as are bromide and chloride anion
      affinities for all four systems determined by Isothermal Titration Calorimetry
      (ITC) in acetonitrile. Although both sets of the strapped calix[4]pyrroles
      displayed enhanced affinities for chloride and bromide anion, differences were
      seen among the various receptors that support the conclusion that the anion
      binding ability of calixpyrrole-type systems can be effectively tuned by
      modifying the length and nature of the bridging straps. In the specific case of
      the diether systems, the largest chloride affinity was seen with the shortest
      strap, whereas the largest affinity for bromide anion was recorded in the case of
      the longest strap. On the basis of these findings, as well as supporting (1)H NMR
      spectroscopic studies, it is postulated that not only cavity size per se, but
      also the ability of the aryl portion of the strap to serve as a CH hydrogen bond
      donor site are important in regulating the observed anion affinities.

PMID- 12797805
TI  - Mechanism of electrophilic chlorination: experimental determination of a
      geometrical requirement for chlorine transfer by the endocyclic restriction test.
AB  - An endocyclic restriction test for acid-catalyzed transfer of chlorine from a
      protonated chloroamine to an aromatic ring provides data that are consistent with
      a transition structure with a large bond angle between the entering and leaving
      groups around chlorine. These results rule out a dissociative mechanism or a
      mechanism that has an oblique angle between the entering and leaving groups.

PMID- 12797806
TI  - Chiral conflict. The effect of temperature on the helical sense of a polymer
      controlled by the competition between structurally different enantiomers: from
      dilute solution to the lyotropic liquid crystal state.
AB  - Helical polymers appended with paired structurally different enantiomers, which
      have opposing helical sense preferences, yield a new kind of relationship between
      optical activity and temperature, and also reveal unusual details of the nature
      of chiral interactions. Consistent with a statistical physical theory developed
      for these experiments, the proportion of the competing chiral groups, determined
      by synthesis, fixes the compensation temperature at which the helical senses are
      equally populated. The lyotropic liquid crystal state formed by these polymers
      yields therefore a nematic state at any chosen temperature over a very wide
      range, with a cholesteric state arising with tightening pitch as temperature
      deviates from this point. Far from the nematic temperature, the pitch reaches the
      nanometer scale and therefore the reflection of visible light. Before crossing
      zero at the nematic temperature, the optical activity becomes so large that it
      may be observed with the unaided eye through crossed polarizers.

PMID- 12797807
TI  - Synthesis, structure, and dynamic behavior of cyclopentadienyl-lithium, -sodium,
      and -potassium annelated with bicyclo[2.2.2]octene units: a systematic study on
      site exchange of alkali metals on a cyclopentadienyl ring in tetrahydrofuran.
AB  - Novel cyclopentadienyl (Cp)-alkali metal complexes 1-M and 2-M (M = Li, Na, K),
      in which the Cp ring is annelated with two bicyclo[2.2.2]octene units and
      substituted with a phenyl group for 1 and a tert-butyl group for 2, were
      synthesized, and their structures and dynamic behaviors were investigated by
      means of X-ray crystallography, dynamic (13)C NMR, and DFT calculations. The X
      ray crystallography results indicated that 1-Li, 1-Na, and 2-Na form monomeric
      contact ion pairs (CIP) with three THF molecules coordinated to the metal atom.
      Also, in THF-d(8), all of the 1-M and 2-M form monomeric CIP in the ground state.
      However, variable-temperature (13)C NMR measurements of 1-M and 2-M in THF-d(8)
      demonstrated dynamic behavior in which the metal ion exchanges positions between
      the upper and lower faces of the Cp ring. From a study of the concentration
      dependence of the dynamic behavior, the exchange was found to proceed principally
      as an intramolecular process at concentration ranges lower than 0.2 M. The
      experimentally observed deltaG values for the intramolecular exchange process for
      all the 1-M and 2-M (except for 2-Li, whose intramolecular process was too slow
      to observe) were found to be quite similar in THF-d(8) solution and to fall
      within the range of 12-14 kcal mol(-)(1). Within this range, a tendency was
      observed for the deltaG values to increase as the size of the metal decreased.
      Theoretical calculations (B3LYP/6-31G(d)) afforded considerably large values as
      the gas-phase dissociation energy for 1-M (162.7 kcal mol(-)(1) for M = Li; 131.6
      kcal mol(-)(1) for M = Na; 110.9 kcal mol(-)(1) for M = K) and for 2-M (170.0
      kcal mol(-)(1) for M = Li; 137.5 kcal mol(-)(1) for M = Na; 115.4 kcal mol(-)(1)
      for M = K). These values should be compensated for by a decrease in the solvation
      energies for the metal ions with increasing size, as exemplified by the
      calculated solvation energy for M(+)(Me(2)O)(4), which serves as a model for
      metal ions solvated with four molecules of THF (-122.9 kcal mol(-)(1) for M = Li;
      -94.7 kcal mol(-)(1) for M = Na; -67.7 kcal mol(-)(1) for M = K). This
      compensation results in a small difference in the overall energy for dissociation
      of 1-M or 2-M in ethereal solutions, thus supporting the similar deltaG values
      observed for the intramolecular metal exchange.

PMID- 12797808
TI  - Two-step FRET as a structural tool.
AB  - The power of FRET to study molecular complexes is expanded by the use of two or
      more donor/acceptor pairs. A general theoretical framework for distance
      measurements in three-chromophore systems is presented. Three energy transfer
      schemes applicable to many diverse situations are considered: (I) two-step FRET
      relay with FRET between the first and second chromophores and between the second
      and third, (II) FRET from a single donor to two different acceptors, and (III)
      two-step FRET relay with FRET also between the first and third chromophores.
      Equations for the efficiencies involving multiple energy transfer steps are
      derived for both donor quenching and sensitized emission measurements. The theory
      is supported by experimental data on model systems of known structure using
      steady-state donor quenching, lifetime quenching, and sensitized emission. The
      distances measured in the three-chromophore systems agree with those in two
      chromophore systems and molecular models. Finally, labeling requirements for
      diagnosis of the energy transfer scheme and subsequent distance measurements are
      discussed.

PMID- 12797810
TI  - Additivity and the physical basis of multivalency effects: a thermodynamic
      investigation of the calcium EDTA interaction.
AB  - To better understand the origin of multivalency effects in ligand binding, the
      binding of a series of mono-, bi-, tri- and tetravalent carboxylate ligands to
      Ca(II) was examined by isothermal titration calorimetry (ITC). The data are
      inconsistent with an entropic origin of enhanced affinity, but rather show that
      at least in this instance the multivalency effect is enthalpic in origin.
      Analysis of binding data using the Jencks model shows the addition of incremental
      carboxylate "ligands" produces an unfavorable interaction entropy that is more
      than offset by a strongly favorable interaction enthalpy. The most likely source
      of this interaction enthalpy is the relief of repulsive Coulombic interactions in
      the unbound state. The conformational entropy penalty arising from the
      restriction of flexible dihedrals is negligible, within experimental error. On
      the other hand, an enthalpic contribution from linker restriction contributes
      strongly to the overall thermodynamics of ligand binding. Together, these data
      suggest that enthalpic effects dominate ligand binding, and design strategies
      should seek to optimize these interactions. The incorporation of unfavorable
      interactions in the unbound ligand that are relieved during binding provides an
      important mechanism by which to enhance ligand affinities.

PMID- 12797809
TI  - Spectroscopic study of [Fe2O2(5-Et3-TPA)2]3+: nature of the Fe2O2 diamond core
      and its possible relevance to high-valent binuclear non-heme enzyme
      intermediates.
AB  - The spectroscopic properties and electronic structure of an Fe(2)(III,IV) bis-mu
      oxo complex, [Fe(2)O(2)(5-Et(3)-TPA)(2)](ClO(4))(3) where 5-Et(3)-TPA = tris(5
      ethyl-2-pyridylmethyl)amine, are explored to determine the molecular origins of
      the unique electronic and geometric features of the Fe(2)O(2) diamond core. Low
      temperature magnetic circular dichroism (MCD) allows the two features in the
      broad absorption envelope (4000-30000 cm(-)(1)) to be resolved into 13
      transitions. Their C/D ratios and transition polarizations from variable
      temperature-variable field MCD saturation behavior indicate that these divide
      into three types of electronic transitions; t(2) --> t(2) involving excitations
      between metal-based orbitals with pi Fe-O overlap (4000-10000 cm(-)(1)),
      t(2)/t(2) --> e involving excitations to metal-based orbitals with sigma Fe-O
      overlap (12500-17000 cm(-)(1)) and LMCT (17000-30000 cm(-)(1)) and allows
      transition assignments and calibration of density functional calculations.
      Resonance Raman profiles show the C(2)(h)() geometric distortion of the Fe(2)O(2)
      core results in different stretching force constants for adjacent Fe-O bonds
      (k(str)(Fe-O(long)) = 1.66 and k(str)(Fe-O(short)) = 2.72 mdyn/A) and a small (
      approximately 20%) difference in bond strength between adjacent Fe-O bonds. The
      three singly occupied pi-metal-based orbitals form strong superexchange pathways
      which lead to the valence delocalization and the S = (3)/(2) ground state. These
      orbitals are key to the observed reactivity of this complex as they overlap with
      the substrate C-H bonding orbital in the best trajectory for hydrogen atom
      abstraction. The electronic structure implications of these results for the high
      valent enzyme intermediates X and Q are discussed.

PMID- 12797811
TI  - Controlled aggregation of ME8(n-) binary anions (M = Cr, Mo; E = As, Sb) into one
      dimensional arrays: structures, magnetism and spectroscopy.
AB  - The [ME(8)](n)()(-) ions where M = Cr, Mo; E = As, Sb; n = 2, 3 have been
      prepared from the corresponding E(7)(3)(-) Zintl ions and M(naphthalene)(2)
      precursors. The complexes and their [A(crypt)](+) salts (A = Na, K) are formed in
      20-45% crystalline yields and have been characterized by UV-vis spectroscopy,
      EPR, cyclic voltammetry, magnetic susceptibility, electrospray mass spectrometry
      (ESI-MS) and single-crystal X-ray diffraction. The structures are defined by
      crown-like cyclo-E(8) rings that are centered by transition metals. MoAs(8)(2)(-)
      (2) is a 16 e(-) diamagnetic complex whereas MoSb(8)(3)(-) (5) and the
      CrAs(8)(3)(-) salts (3 and 4) are 17 e(-) paramagnetic complexes. The ESI-MS
      spectra show free and alkali-complexed ME(8)(n)()(-) ions. The K(+) salt of
      CrAs(8)(3)(-) (4) crystallizes in a one-dimensional chain structure of
      [KCrAs(8)](2)(-) repeat units whereas the Na(+) salt (3) as well as 2 and 5
      crystallize in "free ion" structures. The Cr atoms in 3 and 4 are formally d(1)
      Cr(5+) centers that show EPR signals at g = 2.001 with small As hyperfine
      interactions of 3.6 G. The susceptibility of the [KCrAs(8)](2)(-) salt 4 was
      modeled as a 1D Heisenberg antiferromagnet with a small -J/k(B) of 3K arising
      from antiferromagnetic couplings of the d(1) centers whereas 3 shows Curie-Weiss
      behavior. The electrochemical studies show metal-based oxidations for 3-5 but a
      ligand based oxidation for 2. The electronic spectra are interpreted in terms of
      the molecular orbital analysis of Li and Wu. The differences in formal oxidation
      states of the metals is described in terms of a Zintl-Klemm formalism involving
      E(8)(8)(-) rings that are isoelectronic to S(8). The factors governing the
      formation of 1D chains versus free ions are presented.

PMID- 12797812
TI  - Synthesis and characterization of facial and meridional tris-cyclometalated
      iridium(III) complexes.
AB  - The synthesis, structures, electrochemistry, and photophysics of a series of
      facial (fac) and meridional (mer) tris-cyclometalated Ir(III) complexes are
      reported. The complexes have the general formula Ir(C'N)(3) [where C'N is a
      monoanionic cyclometalating ligand; 2-phenylpyridyl (ppy), 2-(p-tolyl)pyridyl
      (tpy), 2-(4,6-difluorophenyl)pyridyl (46dfppy), 1-phenylpyrazolyl (ppz), 1-(4,6
      difluorophenyl)pyrazolyl (46dfppz), or 1-(4-trifluoromethylphenyl)pyrazolyl
      (tfmppz)]. Reaction of the dichloro-bridged dimers [(C'N(2)Ir(mu
      Cl)(2)Ir(C'N)(2)] with 2 equiv of HC( wedge )N at 140-150 degrees C forms the
      corresponding meridional isomer, while higher reaction temperatures give
      predominantly the facial isomer. Both facial and meridional isomers can be
      obtained in good yield (>70%). The meridional isomer of Ir(tpy)(3) and facial and
      meridional isomers of Ir(ppz)(3) and Ir(tfmppz)(3) have been structurally
      characterized using X-ray crystallography. The facial isomers have near identical
      bond lengths (av Ir-C = 2.018 A, av Ir-N = 2.123 A) and angles. The three
      meridional isomers have the expected bond length alternations for the differing
      trans influences of phenyl and pyridyl/pyrazolyl ligands. Bonds that are trans to
      phenyl groups are longer (Ir-C av = 2.071 A, Ir-N av = 2.031 A) than when they
      are trans to heterocyclic groups. The Ir-C and Ir-N bonds with trans N and C,
      respectively, have bond lengths very similar to those observed for the
      corresponding facial isomers. DFT calculations of both the singlet (ground) and
      the triplet states of the compounds suggest that the HOMO levels are a mixture of
      Ir and ligand orbitals, while the LUMO is predominantly ligand-based. All of the
      complexes show reversible oxidation between 0.3 and 0.8 V, versus Fc/Fc(+). The
      meridional isomers are easier to oxidize by ca. 50-100 mV. The phenylpyridyl
      based complexes have reduction potentials between -2.5 and -2.8 V, whereas the
      phenylpyrazolyl-based complexes exhibit no reduction up to the solvent limit of 
      3.0 V. All of the compounds have intense absorption bands in the UV region
      assigned into (1)(pi --> pi) transitions and weaker MLCT (metal-to-ligand charge
      transfer) transitions that extend to the visible region. The MLCT transitions of
      the pyrazolyl-based complexes are hypsochromically shifted relative to those of
      the pyridyl-based compounds. The phenylpyridyl-based Ir(III) tris-cyclometalates
      exhibit intense emission both at room temperature and at 77 K, whereas the
      phenylpyrazolyl-based derivatives emit strongly only at 77 K. The emission
      energies and lifetimes of the phenylpyridyl-based complexes (450-550 nm, 2-6
      micros) and phenylpyrazolyl-based compounds (390-440 nm, 14-33 micros) are
      characteristic for a mixed ligand-centered/MLCT excited state. The meridional
      isomers for both pyridyl and pyrazolyl-based cyclometalates show markedly
      different spectroscopic properties than do the facial forms. Isolated samples of
      mer-Ir(C( wedge )N)(3) complexes can be thermally and photochemically converted
      to facial forms, indicating that the meridional isomers are kinetically favored
      products. The lower thermodynamic stabilities of the meridional isomers are
      likely related to structural features of these complexes; that is, the meridional
      configuration places strongly trans influencing phenyl groups opposite each
      other, whereas all three phenyl groups are opposite pyridyl or pyrazolyl groups
      in the facial complexes. The strong trans influence of the phenyl groups in the
      meridional isomers leads to the observation that they are easier to oxidize,
      exhibit broad, red-shifted emission, and have lower quantum efficiencies than
      their facial counterparts.

PMID- 12797813
TI  - Molecular dynamics of a dendrimer-dye guest-host system.
AB  - We use molecular dynamics to investigate the instantaneous structure of a fourth
      generation (dansyl terminated) dendrimer of propylene amine dissolved in
      CH(2)Cl(2), and of the same system upon the subsequent encapsulation of several
      eosin Y dyes. Calculations, in a cubic box with up to approximately 3500 solvent
      molecules and a maximum of 12 eosins, show that one of the effects of the
      presence of the guest molecules is to "close" the structure of the box where they
      are contained. Multiple entrances-exits of the guest molecules in the dendrimer
      are observed in less than a nanosecond, until the excess eosins are irreversibly
      expelled and their number is finally brought down to the experimental limit of 6.
      The guest molecules are distributed at two main distances from the center of the
      dendrimer and their surroundings are far from static. Eosins move inside the
      hyperbranched molecule in a way similar to what the solvent molecules do and
      sometimes aggregate.

PMID- 12797814
TI  - A study of homonuclear dipolar recoupling pulse sequences in solid-state nuclear
      magnetic resonance.
AB  - Dipolar recoupling pulse sequences are of great importance in magic angle
      spinning solid-state NMR. Recoupling sequences are used for excitation of double
      quantum coherence, which, in turn, is employed in experiments to estimate
      internuclear distances and molecular torsion angles. Much effort is spent on the
      design of recoupling sequences that are able to produce double-quantum coherence
      with high efficiency in demanding spin systems, i.e., spin systems with small
      dipole-dipole couplings and large chemical-shift anisotropies (CSAs). The
      sequence should perform robustly under a variety of experimental conditions. This
      paper presents experiments and computer calculations that extend the theory of
      double-quantum coherence preparation from the strong coupling/small CSA limit to
      the weak coupling limit. The performance of several popular dipole-dipole
      recoupling sequences-DRAWS, POST-C7, SPC-5, R1, and R2-are compared. It is found
      that the optimum performance for several of these sequences, in the weak
      coupling/large CSA limit, varies dramatically, with respect to the sample
      spinning speed, the magnitude and orientation of the CSAs, and the magnitude of
      dipole-dipole couplings. It is found that the efficiency of double-quantum
      coherence preparation by gamma-encoded sequences departs from the predictions of
      first-order theory. The discussion is supported by density-matrix calculations.

PMID- 12797815
TI  - Immobilization of histidine-tagged proteins on nickel by electrochemical dip pen
      nanolithography.
AB  - Dip-pen nanolithography (DPN) is becoming a popular technique to "write"
      molecules on a surface by using the tip of an atomic force microscope (AFM)
      coated with the desired molecular "ink". In this work, we demonstrate that poly
      histidine-tagged peptides and proteins, and free-base porphyrins coated on AFM
      probes, can be chelated to ionized regions on a metallic nickel surface by
      applying an electric potential to the AFM tip in the DPN process. DPN has been
      accomplished in the Tapping Mode of AFM, which creates many possible applications
      of positioning and subsequently imaging biomolecules, especially on soft
      surfaces.

PMID- 12797817
TI  - n-Pentane and isopentane in one-dimensional channels.
AB  - Molecular dynamics studies of n-pentane and isopentane in one-dimensional
      channels of AlPO(4)-5 and a carbon nanotube are reported. Variation of the
      structure and energetics in AlPO(4)-5 along the channel axis of isopentane is
      similar to what has been found for other rigid molecular systems. In n-pentane,
      these properties exhibit more frequent undulations along the channel due to
      flexibility. The end-to-end distance of n-pentane is a function of its position
      along the channel in AlPO(4)-5, suggesting that n-pentane has to alternately
      stretch in the narrow part and destretch or coil in the broader part of the
      channel. n-Pentane lies flat instead of upright on the inner surface of the
      carbon nanotube. Both of the species exhibit diffusive motion in AlPO(4)-5, and
      the self-diffusivity is higher than that in bulk. Isopentane has a higher
      diffusivity than does n-pentane. This is attributed to the higher cross section
      of isopentane, which is closer to the void cross section. Further, the coupling
      of the translational motion with the slower dihedral angle reorientation in the
      case of n-pentane decreases its mobility. Superdiffusive motion is seen for both
      species in the carbon nanotube. These results can be understood in terms of the
      levitation effect.

PMID- 12797816
TI  - A proton-shuttle mechanism mediated by the porphyrin in benzene hydroxylation by
      cytochrome p450 enzymes.
AB  - Benzene hydroxylation is a fundamental process in chemical catalysis. In nature,
      this reaction is catalyzed by the enzyme cytochrome P450 via oxygen transfer in a
      still debated mechanism of considerable complexity. The paper uses hybrid density
      functional calculations to elucidate the mechanisms by which benzene is converted
      to phenol, benzene oxide, and ketone, by the active species of the enzyme, the
      high-valent iron-oxo porphyrin species. The effects of the protein polarity and
      hydrogen-bonding donation to the active species are mimicked, as before (Ogliaro,
      F.; Cohen, S.; de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2000, 122, 12892
      12893). It is verified that the reaction does not proceed either by hydrogen
      abstraction or by initial electron transfer (Ortiz de Montellano, P. R. In
      Cytochrome P450: Structure, Mechanism and Biochemistry, 2nd ed.; Ortiz de
      Montellano, P. R., Ed.; Plenum Press: New York, 1995; Chapter 8, pp 245-303). In
      accord with the latest experimental conclusions, the theoretical calculations
      show that the reactivity is an interplay of electrophilic and radicalar pathways,
      which involve an initial attack on the pi-system of the benzene to produce sigma
      complexes (Korzekwa, K. R.; Swinney, D. C.; Trager, W. T. Biochemistry 1989, 28,
      9019-9027). The dominant reaction channel is electrophilic and proceeds via the
      cationic sigma-complex,( 2)3, that involves an internal ion pair made from a
      cationic benzene moiety and an anionic iron porphyrin. The minor channel proceeds
      by intermediacy of the radical sigma-complex, (2)2, in which the benzene moiety
      is radicalar and the iron-porphyrin moiety is neutral. Ring closure in these
      intermediates produces the benzene oxide product ((2)4), which does not rearrange
      to phenol ((2)7) or cyclohexenone ((2)6). While such a rearrangement can occur
      post-enzymatically under physiological conditions by acid catalysis, the
      computations reveal a novel mechanism whereby the active species of the enzyme
      catalyzes directly the production of phenol and cyclohexenone. This enzymatic
      mechanism involves proton shuttles mediated by the porphyrin ring through the N
      protonated intermediate, (2)5, which relays the proton either to the oxygen atom
      to form phenol ((2)7) or to the ortho-carbon atom to produce cyclohexenone
      product ((2)6). The formation of the phenol via this proton-shuttle mechanism
      will be competitive with the nonenzymatic conversion of benzene oxide to phenol
      by external acid catalysis. With the assumption that (2)5 is not fully
      thermalized, this novel mechanism would account also for the observation that
      there is a partial skeletal retention of the original hydrogen of the activated C
      H bond, due to migration of the hydrogen from the site of hydroxylation to the
      adjacent carbon (so-called "NIH shift" (Jerina, D. M.; Daly, J. W. Science 1974,
      185, 573-582)). Thus, in general, the computationally discovered mechanism of a
      porphyrin proton shuttle suggests thatthere is an enzymatic pathway that converts
      benzene directly to a phenol and ketone, in addition to nonenzymatic production
      of these species by conversion of arene oxide to phenol and ketone. The potential
      generality of protonated porphyrin intermediates in P450 chemistry is discussed
      in the light of the H/D exchange observed during some olefin epoxidation
      reactions (Groves, J. T.; Avaria-Neisser, G. E.; Fish, K. M.; Imachi, M.;
      Kuczkowski, R. J. Am. Chem. Soc. 1986, 108, 3837-3838) and the general
      observation of heme alkylation products (Kunze, K. L.; Mangold, B. L. K.;
      Wheeler, C.; Beilan, H. S.; Ortiz de Montellano, P. R. J. Biol. Chem. 1983, 258,
      4202-4207). The competition, similarities, and differences between benzene
      oxidation viz. olefin epoxidation and alkanyl C-H hydroxylation are discussed,
      and comparison is made with relevant experimental and computational data. The
      dominance of low-spin reactivity in benzene hydroxylation viz. two-state
      reactivity (Shaik, S.; de Visser, S. P.; Ogliaro, F.; Schwarz, H.; Schroder, D.
      Curr. Opin. Chem. Biol. 2002, 6, 556-567) in olefin epoxidation and alkane
      hydroxylation is traced to the loss of benzene resonance energy during the bond
      activation step.

PMID- 12797818
TI  - Three-coordinate aluminum in zeolites observed with in situ x-ray absorption near
      edge spectroscopy at the Al K-edge: flexibility of aluminum coordinations in
      zeolites.
AB  - Application of in situ X-ray absorption near-edge spectroscopy (XANES) at the Al
      K-edge provides unique insight into the flexibilty of the aluminum coordinations
      in zeolites as a function of treatment or during true reaction conditions. A
      unique, previously not observed, pre-edge feature is detected in zeolites H
      Mordenite and steamed and unsteamed H-Beta at temperatures above 675 K. Spectra
      simulations using the full multiple scattering code Feff8 identify the unique pre
      edge feature as three-coordinate aluminum. The amount of three-fold coordinated
      aluminum is a function of temperature and pretreatment of a zeolite: a steamed
      zeolite Beta contains more three-coordinate aluminum than an unsteamed sample. No
      clear differences between zeolites H-Mordenite and H-Beta were observed.
      Octahedrally coordinated aluminum forms in zeolites H-Mordenite and H-Beta at
      room temperature in a stream of wet helium. This octahedrally coordinated
      aluminum is unstable at temperatures higher than 395 K, where it quantitatively
      reverts to the tetrahedral coordination.

PMID- 12797819
TI  - In situ FTIR studies of primary intermediates of photocatalytic reactions on
      nanocrystalline TiO2 films in contact with aqueous solutions.
AB  - Multiple internal reflection infrared spectroscopy was applied to in situ
      investigations of surface intermediates of photocatalytic reactions on
      nanocrystalline TiO(2) films in contact with aqueous solutions. UV irradiation in
      the presence of dissolved O(2) caused the appearance of new bands peaked at 943,
      838, and 1250-1120 cm(-)(1) together with intensity changes in other bands.
      Investigations of influences of the solution pH, the presence or absence of hole
      and electron scavengers, and isotopic H(2)O --> D(2)O exchange on the spectral
      changes have revealed that the primary step of photocatalytic O(2) reduction is
      the formation of the surface peroxo species, Ti(O(2)), giving the 943 cm(-)(1)
      band, probably with the surface superoxo species, TiOO., as a precursor, in
      neutral and acidic solutions. The surface peroxo species is then transformed to
      the surface hydroperoxo, TiOOH, giving the 838 and 1250-1120 cm(-)(1) bands, by
      protonation in the dark. This is, to our knowledge, the first direct in situ
      spectroscopic detection of primary intermediates for the photocatalytic O(2)
      reduction in aqueous solutions. On the basis of the assignment, a possible
      reaction scheme for various processes of the photocatalytic O(2) reduction is
      proposed, which is in harmony with other spectral changes induced by the UV
      irradiation.

PMID- 12797820
TI  - Solid state separated-local-field NMR spectroscopy on half-integer quadrupolar
      nuclei: principles and applications to borane analysis.
AB  - New multidimensional NMR methods correlating the quadrupolar and heteronuclear
      dipolar interactions affecting a half-integer quadrupolar spin in the solid state
      are introduced and exemplified. The methods extend separated-local-field magic
      angle spinning (SLF MAS) NMR techniques that have been used successfully in spin
      (1)/(2) spectroscopy to the study of S >/= (3)/(2) nuclei. In our implementation,
      these techniques avoid homonuclear proton decoupling requirements by relying on
      moderately fast MAS rates (6-15 kHz) and use rotor-synchronized constant-time
      pulse sequences to achieve nearly arbitrary amplifications of the apparent
      dipolar coupling strengths. The result is a suite of simple 2D NMR experiments,
      whose line shapes carry valuable information about the structure and dynamics of
      solids containing quadrupolar and proton nuclei. The potential of these sequences
      was exploited to gather new insight into the structure and dynamics of a variety
      of boron-containing samples. These experimental SLF schemes were also extended to
      3D NMR experiments that incorporate multiple-quantum MAS, thus enabling the
      resolution needed to study multiple chemical sites in a solid and providing a
      useful tool for the assignment of inequivalent sites.

PMID- 12797821
TI  - Gas phase dissociation energies of saturated AHn*+ radical cations and AHn
      neutrals (A = Li-F, Na-Cl): dehydrogenation, deprotonation, and formation of AHn
      2*+ - H2 complexes.
AB  - The dissociation energies corresponding to the two possible A-H cleavages of A (A
      = Li-F and Na-Cl) radical cations (loss of a H(+) and loss of a H(.)) have been
      computed at the CCSD(T)/ 6-311++G(3df,2pd) level of theory and compared to those
      of their neutral precursors. Removing an electron from AH(n)() decreases
      dramatically its deprotonation energy, especially for the A molecules (C and ),
      which become one of the most acidic species of the row, their acid character
      being only exceeded by FH(.+) and ClH(.+), respectively. However, dehydrogenation
      energies only decrease for the systems on the left side of the row (up to C and
      SiH(4)(.+)) for which the electron is removed from a A-H bonding orbital.
      Nevertheless, the loss of hydrogen is the more favorable cleavage in all cases
      except FH(.+). Ionization of SiH(4) leads to a Jahn-Teller distorted structure
      that corresponds to a Si - H(2) complex. Other - eta(2)H(2) complexes in the
      doublet spin state have also been found to be stable for A = Be, Mg, Al, and P,
      the hydrogen molecule complexes being more stable than their corresponding
      radical cations, for Be, Mg, and Al.

PMID- 12797822
TI  - The theory of electron transfer reactions: what may be missing?
AB  - Molecular dynamics simulations are presented for condensed-phase electron
      transfer (ET) systems where the electronic polarizability of both the solvent and
      the solute is incorporated. The solute polarizability is allowed to change with
      electronic transition. The results display notable deviation from the standard
      free energy parabolas of traditional ET theories. A new three-parameter ET model
      is applied, and the theory is shown to accurately model the free energy surfaces.
      This paper presents conclusive evidence that the traditional theory for the free
      energy barrier of ET reactions requires modification.

PMID- 12797824
TI  - Radical carbon skeleton rearrangements: catalysis by coenzyme B12-dependent
      mutases.

PMID- 12797825
TI  - Radical catalysis in coenzyme B12-dependent isomerization (eliminating)
      reactions.

PMID- 12797826
TI  - S-Adenosylmethionine: a wolf in sheep's clothing, or a rich man's
      adenosylcobalamin?

PMID- 12797827
TI  - Biological radical sulfur insertion reactions.

PMID- 12797828
TI  - Radical initiation in the class I ribonucleotide reductase: long-range proton
      coupled electron transfer?

PMID- 12797829
TI  - Structure and function of DNA photolyase and cryptochrome blue-light
      photoreceptors.

PMID- 12797830
TI  - Mechanism of free radical oxygenation of polyunsaturated fatty acids by
      cyclooxygenases.

PMID- 12797831
TI  - Autocatalytic radical reactions in physiological prosthetic heme modification.

PMID- 12797832
TI  - Pyruvate ferredoxin oxidoreductase and its radical intermediate.

PMID- 12797833
TI  - Free radical catalysis by galactose oxidase.

PMID- 12797834
TI  - Tetrahydrobiopterin radical enzymology.

PMID- 12797835
TI  - Mechanistic studies on the hydroxylation of methane by methane monooxygenase.

PMID- 12797836
TI  - Quantum chemical studies of radical-containing enzymes.

PMID- 12797837
TI  - Occurrence of chronic disease in former top-level athletes. Predominance of
      benefits, risks or selection effects?
AB  - Former elite athletes from most sports disciplines have lower overall morbidity
      risk and enjoy better self-rated health in later years compared with the general
      population and matched controls who were healthy at young age. This is seen
      particularly among former endurance athletes who have a lower incidence of
      coronary heart disease and type 2 diabetes mellitus. Most often data are
      available only for men. Based on the available data, participation in elite
      sports cannot be regarded as an overall health hazard. However, aside from a high
      risk of acute injury in specific sports, possible negative effects of long
      standing athletic activity on the development of osteoarthritis should not be
      neglected. It should also be remembered that elite athletes are a biologically
      and genetically select group who are not representative of the population at
      large. Given the nature of the available data, the possible health consequences
      of recent changes in different characteristics of sports, such as training
      practices, professionalism and use of doping, cannot be properly predicted.

PMID- 12797838
TI  - Recommendations for return to sports following cervical spine injuries.
AB  - The decision of return to play following cervical spine injuries can be one of
      the most challenging with a wide variation in opinion as far as management. The
      onus is on the physician to consider the risks of continued play for patients who
      have experienced a cervical spine injury and who are reluctant to give up their
      sport of choice. In general, the literature shows agreement for the basic
      necessities for return to collision sports to include: normal strength, painless
      range of motion, a stable vertebral column and adequate space for the
      neurological elements. In addition, return to play in an unsafe environment is
      contraindicated. Playing with defective equipment or with improper technique has
      been associated with catastrophic injuries and should be avoided. This
      particularly includes: spear tackling, diving in unknown or shallow water, diving
      while intoxicated, checking from behind in hockey or using a trampoline without
      spotting equipment. However, there is a lack of consensus on returning to play
      with the following: stenosis, spear tackler's spine, loss of normal lordosis or
      range of motion, surgically corrected instability, ligamentous instability less
      than that defined by White/Panjabi, transient quadriparesis, healed disc
      herniation and congenital fusion. More informed decisions can be made by
      physician and patient using a basic knowledge of: (i) previous clinical
      experience, including that outlined in published epidemiological studies and
      guidelines; (ii) biomechanical data defined in the laboratory; and (iii) the
      priorities of the patient.

PMID- 12797839
TI  - Regression to the mean. A threat to exercise science?
AB  - Regression to the mean (RTM) can bias any investigation where the response to
      treatment is classified relative to initial values for a given variable without
      the use of an appropriate control group. The phenomenon and resulting errors of
      interpretation have been recognised by clinicians in a number of disciplines. The
      causes of RTM include both intra-individual variance and measurement error. The
      magnitude of RTM can be estimated quite simply, given a knowledge of intra- and
      inter-individual variance. RTM can be avoided by using a fully controlled
      experimental design. Difficulties can also be minimised by making duplicate
      measurements prior to the experimental manipulation, the first measurement
      serving for classification, and the second (with randomly distributed variance)
      allowing an assessment of the response to treatment. Less satisfactorily,
      surrogate measurements (for example, plasma volume for maximal oxygen intake
      [VO2(max)]) can assess the bias introduced by an initial non-random sorting of
      study participants. The impact of RTM on the design and interpretation of
      investigations has as yet received little consideration by exercise scientists
      and sports physicians. The response to training is often related to initial
      measurements of a dependent variable such as heart size, ST segmental depression,
      fitness or level of physical activity. In particular, analyses of this type have
      been adduced to support the belief that the response to aerobic training is
      inversely related to an individual's VO2(max). In fact, RTM may account for a
      major part of this apparent relationship.

PMID- 12797840
TI  - Exercise in hypertension. A clinical review.
AB  - The current exercise prescription for the treatment of hypertension is:
      cardiovascular mode, for 20-60 minutes, 3-5 days per week, at 40-70% of maximum
      oxygen uptake (VO2(max)). Cardiovascular exercise training is the most effective
      mode of exercise in the prevention and treatment of hypertension. Resistance
      exercise is not the preferred mode of exercise treatment, but can be incorporated
      into an exercise regime provided the diastolic blood pressure response is within
      safe limits. It is inconclusive whether durations longer than 30 minutes produce
      significantly greater reductions in blood pressure. A frequency of three exercise
      sessions per week has been considered to be the minimal frequency for blood
      pressure reduction. Higher frequencies tended to produce greater reductions,
      although not significantly different. Evidence still exists that high intensity
      exercise (>75% VO2(max)) may not be as effective as low intensity exercise (<70%
      VO2(max)) in reducing elevated blood pressures. Exercise can be effective without
      a change in bodyweight or body fat. Bodyweight or body fat loss and anti
      hypertensive medications do not have an added effect on blood pressure reduction
      associated with exercise. beta-blockade is not the recommended anti-hypertensive
      medication for effective exercise performance in non-cardiac patients. Not all
      hypertensive patients respond to exercise treatment. Differences in genetics and
      pathophysiology may be responsible for the inability of some hypertensive
      patients to respond to exercise. Ambulatory technology may allow advances in
      individualising a more effective exercise prescription for low-responders and non
      responders.

PMID- 12797841
TI  - The exercise-induced growth hormone response in athletes.
AB  - Human growth hormone (hGH) is secreted in a pulsatile fashion, generally
      following a circadian rhythm. A number of physiological stimuli can initiate hGH
      secretion, the most powerful, non-pharmacological of which are sleep and
      exercise. hGH has many varied roles throughout life, from growth itself,
      including the turnover of muscle, bone and collagen, to the regulation of
      selective aspects of metabolic function including increased fat metabolism and
      the maintenance of a healthier body composition in later life. The exercise
      induced growth hormone response (EIGR) is well recognised and although the exact
      mechanisms remain elusive, a number of candidates have been implicated. These
      include neural input, direct stimulation by catecholamines, lactate and or nitric
      oxide, and changes in acid-base balance. Of these, the best candidates appear to
      be afferent stimulation, nitric oxide and lactate. Resistance training results in
      a significant EIGR. Evidence suggests that load and frequency are determining
      factors in the regulation of hGH secretion. Despite the significant EIGR induced
      by resistance training, much of the stimulus for protein synthesis has been
      attributed to insulin-like growth factor-1 with modest contributions from the hGH
      GH receptor interaction on the cell membrane. The EIGR to endurance exercise is
      associated with the intensity, duration, frequency and mode of endurance
      exercise. A number of studies have suggested an intensity 'threshold' exists for
      EIGR. An exercise intensity above lactate threshold and for a minimum of 10
      minutes appears to elicit the greatest stimulus to the secretion of hGH. Exercise
      training above the lactate threshold may amplify the pulsatile release of hGH at
      rest, increasing 24-hour hGH secretion. The impact of chronic exercise training
      on the EIGR remains equivocal. Recent evidence suggests that endurance training
      results in decreased resting hGH and a blunted EIGR, which may be linked to an
      increased tissue sensitivity to hGH. While the potential ergogenic effects of
      exogenous GH administration are attractive to some athletes, the abuse of GH has
      been associated with a number of pathologies. Identification of a training
      programme that will optimise the EIGR may present a viable alternative. Ageing is
      often associated with a progressive decrease in the volume and, especially, the
      intensity of exercise. A growing body of evidence suggests that higher intensity
      exercise is effective in eliciting beneficial health, well-being and training
      outcomes. In a great many cases, the impact of some of the deleterious effects of
      ageing could be reduced if exercise focused on promoting the EIGR. This review
      examines the current knowledge and proposed mechanisms for the EIGR, the
      physiological consequences of endurance, strength and power training on the EIGR
      and its potential effects in elderly populations, including the aged athlete.

PMID- 12797843
TI  - Expanding the frontiers of women's health research--US style.

PMID- 12797842
TI  - Dairy products, meat and sports performance.
AB  - Creatine supplementation improves repetitive, short-term performance. It has not
      been shown that exclusion of meat from the diet would impair repetitive short
      term performance. In contrast, reduction of protein intake and a concomitant
      increase of carbohydrate intake during a period of 3-5 days improves anaerobic (2
      7 minutes) performance. The protein intake in a mixed or lacto-vegetarian diet is
      adequate even for elite athletes, providing that energy requirements are met.
      Many dietary supplements have been suggested to increase muscle mass and/or to
      decrease fat mass. Although the effects of conjugated linoleic acid on body
      composition in athletes are not clear, some positive findings in untrained, obese
      individuals call for more studies. Strenuous training may impair immune function
      and increase the susceptibility to infections. Exclusion of meat from the diet
      does not seem to have adverse effects on immune function. Glutamine
      supplementation (>3-6 g/day) may improve immune function, but more studies are
      needed. Similarly, more studies on the possible effects of whey protein and
      probiotic supplementation on immune function and performance in physically highly
      active individuals are warranted. Vitamin and mineral balance are not usually a
      problem among athletes. Notable exceptions may be calcium and iron in some
      females. Increased calcium intake in athletes with hormonal and menstrual
      disturbances could theoretically help in maintaining bone status; however, no
      data are available. A diet with meat may help in maintaining adequate iron
      stores.

PMID- 12797844
TI  - Risk-taking behaviour of young women in Australia: screening for health-risk
      behaviours.
AB  - Healthy risk-taking is a normal part of adolescence. Young people who participate
      in multiple risk-taking increase the chance of damaging their health. There
      appears to be a growing range and prevalence of health-risk behaviours among
      young women, notably in their use of alcohol and marijuana. Research suggests
      that such health-risk behaviours may be related to psychological factors such as
      stress and depression. General practitioners have a central role in identifying
      and preventing health-risk behaviours and associated mental health problems in
      young people. Comprehensive assessment includes a series of screening questions
      about home, education (or employment), activities, drugs, sexuality and suicide
      for young people, known as the HEADSS technique.

PMID- 12797845
TI  - Dieting, body weight, body image and self-esteem in young women: doctors'
      dilemmas.
AB  - Many young women feel that body image and exercise are important for their self
      esteem, want to lose weight, are afraid they might gain weight, and feel fat.
      Interventions that improve self-esteem, encourage communication and help
      adolescents to be supportive of each other may prevent some of these women from
      developing eating disorders. If an eating disorder is suspected, it may be useful
      for physicians to ask about fear of loss of control over the body, eating, weight
      and shape; and preoccupation with food, eating, nutrition, body weight and shape,
      as these issues may differentiate those at greater risk.

PMID- 12797846
TI  - The baby bust.

PMID- 12797847
TI  - Multiple pregnancy: a modern epidemic?

PMID- 12797848
TI  - New contraceptive choices across reproductive life.
AB  - The range of contraceptive options and consumer awareness of new contraceptive
      methods have both increased significantly over the past 10 years. New methods
      available in Australia include lower-dose oral contraceptive pills, new oral
      progestogens, progestogen implants, a progestogen-bearing intrauterine device and
      polyurethane female condoms. Contraceptive options which may soon be introduced
      in Australia include novel methods of administering combined (oestrogen
      progestogen) contraception, such as dermal patches and vaginal rings.

PMID- 12797849
TI  - The efficacy of non-contraceptive uses for hormonal contraceptives.
AB  - In addition to providing safe and effective contraception, both the combined oral
      contraceptive pill (COCP) and selected long-acting progestogen-only
      contraceptives have significant health benefits. The COCP may reduce menstrual
      blood loss, dysmenorrhoea and premenstrual syndrome; unequivocally reduces the
      later incidence of endometrial and ovarian cancer; appears to help protect future
      fertility, probably by reducing the risk of acute pelvic inflammatory disease,
      endometriosis and uterine fibroids. The quality of evidence for individual non
      contraceptive health benefits of the COCP is very variable.

PMID- 12797851
TI  - Hormone replacement therapy: to use or not to use?
AB  - The main indication for hormone replacement therapy (HRT) is to control
      menopausal symptoms and improve quality of life. Ideally, withdrawal of HRT
      should be attempted after 4-5 years of therapy. HRT reduces fracture risk and
      remains appropriate therapy for osteoporosis, particularly in women with
      symptoms. HRT is not appropriate for primary or secondary cardioprotection. HRT
      leads to a small increase in breast cancer incidence, which increases with
      duration of therapy and age. HRT increases the risk of thromboembolism. Patient
      management and therapy should be reviewed annually with risk-benefit counselling.

PMID- 12797850
TI  - Update on treatment of menstrual disorders.
AB  - There is evidence from well designed randomised controlled trials that modern
      medical and conservative surgical therapies (including endometrial ablation) are
      effective treatments for heavy menstrual bleeding for many women. Submucous
      fibroids may be resected directly via the hysteroscope, reducing menstrual
      bleeding, although data are available only from case series. Endometriosis is
      common, may also occur in young women and may present with atypical or non
      cyclical symptoms; conservative laparoscopic surgery increases fecundity and
      reduces dysmenorrhoea and dyspareunia. Randomised trials of the levonorgestrel
      intrauterine system in women with menorrhagia have shown that hysterectomy can be
      avoided in 80% of cases, and that this system is an effective therapy for
      menorrhagia. The levonorgestrel intrauterine system may also be useful for
      managing symptoms of endometriosis, adenomyosis and endometrial hyperplasia,
      based on observational data.

PMID- 12797852
TI  - Menopause: new therapies.
AB  - The risk-benefit ratio of traditional postmenopausal hormone therapy is
      considered by many to be unacceptable. Low-dose oestrogen-progestin therapy (oral
      or non-oral and continuous or pulsatile) may have a better risk-benefit ratio,
      but this remains unproven. Steroids with selective tissue activation, such as
      tibolone, alleviate symptoms and protect against bone loss, but long-term safety
      data are lacking. Selective oestrogen receptor modulators (SERMs), such as
      raloxifene, prevent bone loss when used alone, and may soon be combined with
      oestradiol to treat symptoms and prevent osteoporotic fracture. Effects of SERMs
      on the cardiovascular system are currently being evaluated.

PMID- 12797854
TI  - Older women's sexuality.
AB  - In consultations with older women, doctors should ask about sexual problems. A
      holistic approach is needed to examine the many different factors that can affect
      sexuality. Hormonal changes associated with ageing have an impact on women's
      sexuality. Doctors need to have a clear idea of the place of hormonal treatment
      for different sexual problems. Physical changes associated with ageing, including
      illness and disability, may interfere with sexual expression. Diseases of the
      endocrine, vascular and nervous systems will most commonly affect sexual
      function. A broad range of psychosocial factors associated with ageing may
      influence sexuality.

PMID- 12797853
TI  - Arousal disorders in women: complaints and complexities.
AB  - Female sexual arousal disorders constitute a varied spectrum of difficulties,
      ranging from the total absence of genital or subjective pleasurable arousal to
      feelings of persistent genital arousal in the absence of sexual desire. Arousal
      disorders can be associated with physical factors (eg, vaginal dryness) or
      psychological factors (eg, anxiety, distraction), or a combination of both. The
      most common complaint is the absence of subjective sexual excitement or pleasure
      despite adequate physical arousal (eg, lubrication). Pharmacological and physical
      treatments include the use of oestrogen, lubricants and vibrators. There may be a
      place for drugs that increase vasocongestion and vasodilation. Psychological
      therapy addresses inhibitions, and interpersonal and motivational factors.

PMID- 12797855
TI  - Lesbian health inequalities: a cultural minority issue for health professionals.
AB  - Health inequalities exist for lesbian and bisexual women, largely related to
      experiences of discrimination, homophobia and heterosexism. These issues can lead
      to avoidance of routine healthcare and screening and reduced disclosure of sexual
      orientation within consultations. Lesbian and bisexual women have specific
      healthcare needs in areas of sexual and cervical health, reproductive health and
      parenting, mental health, substance use, and ageing. Facilitation of disclosure
      of sexual orientation, identity and behaviour within the consultation is desired
      by most lesbians and important for addressing specific health needs. Healthcare
      providers should develop "cultural competence" in lesbian issues to enhance their
      care of lesbian and bisexual women. Healthcare providers have a role in promoting
      awareness of lesbian health issues and inequalities in the arenas of healthcare
      provider education, research and health policy.

PMID- 12797856
TI  - Breast self examination: be alert but not alarmed?

PMID- 12797857
TI  - Can we really beat cervical cancer?

PMID- 12797858
TI  - Breast cancer screening.
AB  - Achieving and maintaining a high rate of attendance for screening and two-yearly
      re-screening is essential for the success of the BreastScreen Australia program.
      A low participation rate will result in fewer breast cancer-related deaths being
      prevented. Results of two recent large randomised trials do not show that a
      systematic approach to breast self examination finds breast cancers early or
      impacts on survival. "Breast awareness" and the prompt reporting of breast
      symptoms are important early detection messages for women of all ages. General
      practitioners have a key role in the promotion and provision of information about
      effective public-health initiatives for the early detection of breast cancer.

PMID- 12797859
TI  - Prevention of cervical cancer.
AB  - Cervical screening in Australia is a successful public health initiative. Since
      the introduction of the National Cervical Screening Program in 1991, there has
      been a significant fall in incidence of and mortality from cervical cancer.
      Laboratory quality procedures are critical to ensuring optimal outcomes.
      Laboratory accreditation procedures are being reviewed in line with recent
      government recommendations. For a sustainable program, cost-containment issues
      need to be considered; screening interval, management of screen-detected
      abnormalities, and new technologies are the critical drivers of cost.

PMID- 12797860
TI  - Screening for ovarian cancer.
AB  - Ovarian cancer is the leading cause of death from gynaecological malignancies. No
      precancerous lesions have been identified. Bimanual examination has not been
      proven to be of value as a screening test. Transvaginal ultrasound examination,
      with or without measurement of CA 125 levels, is currently being evaluated for
      population screening. Women at high risk of ovarian cancer should be screened
      annually - with measurement of CA 125 level and transvaginal ultrasound
      examination.

PMID- 12797861
TI  - Screening for endometrial cancer.
AB  - Routine screening for endometrial carcinoma is currently not justified.
      Postmenopausal women need to be educated about the importance of seeking
      attention if any vaginal bleeding occurs. All postmenopausal bleeding requires
      review and appropriate investigation. Women taking tamoxifen have a higher risk
      of endometrial cancer and should report any bleeding or spotting; however,
      ultrasound screening is not recommended for asymptomatic women taking tamoxifen.
      Families with hereditary non-polyposis colon cancer have a higher risk of
      endometrial cancer and require counselling about this risk. A Pap test is not a
      screening test for endometrial cancer, but the incidental finding of endometrial
      cells on a Pap smear in a postmenopausal woman requires investigation.

PMID- 12797862
TI  - James Marion Sims: some speculations and a new position.

PMID- 12797863
TI  - Sepsis induces the transcription of the glucocorticoid receptor in skeletal
      muscle cells.
AB  - Evidence from a recent study indicates that glucocorticoids (GCs) mediate
      skeletal muscle proteolysis during sepsis via the GC receptor (GR) pathway.
      Attempts to identify the mechanisms regulating GR gene expression in skeletal
      muscle during sepsis have been hampered by the lack of an appropriate in vitro
      model system that can mimic in vivo septic conditions. In the present study, we
      report that GR gene transcription in L6 myocytes in vitro is up-regulated by
      treatment with sera from septic rats in a manner similar to that measured in
      septic rats in vivo. Sera from septic rats were collected from animals in which
      sepsis was induced by caecal ligation and puncture and from control rats that
      were sham-operated. Finally, by treating L6 myotubes with the GR antagonist RU
      38486, thereby preventing sepsis-induced GR transcription, we confirmed that the
      possible septic effect on the GR was due to increased GCs. L6 myocytes treated
      with sera from septic rats might therefore be useful as an experimental model for
      identifying the molecular mechanisms by which the GR regulates muscle cachexia
      during sepsis. Furthermore, RU 38486 inhibited the sepsis-induced increase in
      total and myofibrillar energy-dependent protein breakdown rates in incubated
      extensor digitorum longus muscles from septic and sham-operated rats, as measured
      by release of tyrosine and 3-methylhistidine respectively. Our results
      demonstrate for the first time that sepsis induces GR transcription in skeletal
      muscle, and supports the hypothesis that the GC-induced proteolysis under sepsis
      is partially a consequence of GR activation.

PMID- 12797864
TI  - Nitration of endogenous para-hydroxyphenylacetic acid and the metabolism of
      nitrotyrosine.
AB  - Reactive nitrogen species, such as peroxynitrite, can nitrate tyrosine in
      proteins to form nitrotyrosine. Nitrotyrosine is metabolized to 3-nitro-4
      hydroxyphenylacetic acid (NHPA), which is excreted in the urine. This has led to
      the notion that measurement of urinary NHPA may provide a time-integrated index
      of nitrotyrosine formation in vivo. However, it is not known whether NHPA is
      derived exclusively from metabolism of nitrotyrosine, or whether it can be formed
      by nitration of circulating para -hydroxyphenylacetic acid (PHPA), a metabolite
      of tyrosine. In the present study, we have developed a gas chromatography MS
      assay for NHPA and PHPA to determine whether or not NHPA can be formed directly
      by nitration of PHPA. Following the injection of nitrotyrosine, 0.5+/-0.16% of
      injected dose was recovered unchanged as nitrotyrosine, and 4.3+/-0.2% as NHPA in
      the urine. To determine whether or not NHPA could be formed by the nitration of
      PHPA, deuterium-labelled PHPA ([(2)H(6)]PHPA) was injected, and the formation of
      deuterated NHPA ([(2)H(5)]NHPA) was measured. Of the infused [(2)H(6)]PHPA, 78+/
      2% was recovered in the urine unchanged, and approx. 0.23% was recovered as
      [(2)H(5)]NHPA. Since the plasma concentration of PHPA is markedly higher than
      free nitrotyrosine (approx. 400-fold), the nitration of high-circulating
      endogenous PHPA to form NHPA becomes very significant and accounts for the
      majority of NHPA excreted in urine. This is the first study to demonstrate that
      NHPA can be formed by nitration of PHPA in vivo, and that this is the major route
      for its formation.

PMID- 12797866
TI  - Expression and characterization of an anti-(hepatitis B surface antigen)
      glycosylated mouse antibody in transgenic tobacco (Nicotiana tabacum) plants and
      its use in the immunopurification of its target antigen.
AB  - Transgenic plants expressing recombinant immunoglobulins have arisen as an
      alternative technology for the large-scale production of antibodies useful in
      therapeutics and in industrial processes. In the present paper we report the
      expression in transgenic tobacco ( Nicotiana tabacum ) of an anti-HBsAg [anti
      (hepatitis B virus surface antigen)] mouse IgG1 mAb (monoclonal antibody),
      currently used for the industrial purification of the recombinant vaccine
      antigen. Using the sweet potato sporamin signal peptide, a KDEL (Lys-Asp-Glu-Leu)
      ER (endoplasmic reticulum) anchorage domain, and a heavy- and light-chain gene
      tandem construction, we generated F1 plants in which the expression of the
      antibody accounted for 0.5% of the total soluble proteins. The 'plantibody'
      (functional IgG antibody produced in plants) was easily purified by Protein A
      Sepharose chromatography with a yield of approximately 35 microg/g of fresh leaf
      material, and its glycosylation indicated that, irrespective of the KDEL signal,
      the molecule is modified in both the ER and Golgi. Finally, a successful
      comparison of the plantibody with the ascites-derived mAb in the immunoaffinity
      purification of the vaccine recombinant HBsAg was performed. Taken as a whole,
      our results show that the large-scale production of this antibody of industrial
      relevance in transgenic tobacco is feasible.

PMID- 12797865
TI  - Differential expression, localization and activity of two alternatively spliced
      isoforms of human APC regulator CDH1.
AB  - The timely destruction of key regulators through ubiquitin-mediated proteolysis
      ensures the orderly progression of the cell cycle. The APC (anaphase-promoting
      complex) is a major component of this degradation machinery and its activation is
      required for the execution of critical events. Recent studies have just begun to
      reveal the complex control of the APC through a regulatory network involving WD40
      repeat proteins CDC20 and CDH1. In the present paper, we report on the
      identification and characterization of human CDH1beta, a novel alternatively
      spliced isoform of CDH1. Both CDH1alpha and CDH1beta can bind to the APC and
      stimulate the degradation of cyclin B1, but they are differentially expressed in
      human tissues and cells. CDH1alpha contains a nuclear localization signal which
      is absent in CDH1beta. Intracellularly, CDH1alpha appears in the nucleus whereas
      CDH1beta is a predominantly cytoplasmic protein. The forced overexpression of
      CDH1alpha in cultured cells correlates with the reduction of nuclear cyclin A,
      but the steady-state amount of cyclin A does not change noticeably in CDH1beta
      overexpressed cells. In Xenopus embryos, ectopic overexpression of human
      CDH1alpha, but not of CDH1beta, induces cell-cycle arrest during the first G(1)
      phase at the mid-blastula transition. Taken together, our findings document the
      differential expression, subcellular localization and cell-cycle-regulatory
      activity of human CDH1 isoforms.

PMID- 12797868
TI  - The etiology and outcome of pneumonia in human immunodeficiency virus-infected
      children admitted to intensive care in a developing country.
AB  - In developing countries, many human immunodeficiency virus (HIV)-infected
      children require intensive care unit (ICU) resources for pneumonia, but there is
      little information on the etiology of pneumonia or the impact of ICU
      intervention. OBJECTIVE: To compare the etiology and outcome of pneumonia in HIV
      positive and seronegative children admitted to ICU. DESIGN: Prospective study.
      SETTING: Two pediatric ICUs linked to the University of Cape Town, South Africa.
      PATIENTS: Consecutive children admitted for pneumonia during 1998. MEASUREMENTS
      AND MAIN RESULTS: Clinical, demographic, ventilatory, and laboratory data were
      collected. Blood for testing was obtained. Induced sputum or nondirected
      bronchoalveolar lavage was performed for culture and Pneumocystis carinii
      identification; gastric lavage (GL) provided specimens for mycobacterial culture.
      Seventy-six children (21 [27.6%, 95% confidence interval {CI} = 18-39.1] HIV
      positive) were enrolled. At admission, HIV infection was diagnosed in 15 of the
      21 (71.4% [47.8-88.7]) HIV-positive patients. P. carinii pneumonia occurred in
      eight HIV-positive children (38% of HIV-infected patients) and one HIV-negative
      child. It was the acquired immunodeficiency syndrome (AIDS)-defining illness in
      seven children (47%). The incidence of bacteremia (15.3%) was similar in HIV
      positive (15.8%) and HIV-negative children (15.1%), p =.94; Streptococcus
      pneumoniae and Staphylococcus aureus were the predominant isolates. Bacterial and
      viral isolates from sputum or bronchoalveolar lavage, including Mycobacterium
      tuberculosis in six (8%) children, did not differ by HIV status. Intermittent
      positive pressure ventilation was used in 8 of 21 (38%) HIV-positive children and
      28 of 55 (51%) HIV-negative children, p =.32. Median days of intermittent
      positive pressure ventilation (3 [2-6]), ICU (5 [3-9.5]), and hospital (11 [7.5
      19]) did not vary by HIV status. The in-hospital mortality rate for HIV-positive
      children (6 of 21 [28.6%]) was double that for seronegative patients (8 of
      55[14.5%], relative risk [RR] 1.96 [0.77-4.99], p =.16). CONCLUSION: More than a
      quarter of children admitted to ICU for pneumonia in this geographic area are HIV
      positive; most are diagnosed with HIV at admission. P. carinii pneumonia is a
      common AIDS indicator disease. HIV-infected children admitted with pneumonia had
      a worse outcome than seronegative children, a difference that is rendered
      statistically insignificant by the small sample size.

PMID- 12797869
TI  - Effectiveness and safety of a protocol for promotion of early intragastric
      feeding in critically ill children.
AB  - OBJECTIVES: To investigate the feasibility, adequacy, and efficacy of early
      poststress intragastric feeding (EPIGF) in critically ill children. DESIGN: A
      prospective clinical study. SETTING: Pediatric intensive care unit in a tertiary
      care children's hospital. PATIENTS: Seventy-one consecutively enrolled critically
      ill children requiring prolonged mechanical ventilation. INTERVENTIONS: Full
      strength intragastric tube feedings (Nutrison Pediatric, Standard) were initiated
      within 12 hrs of the study-entry event. Enteral feedings were advanced to a
      target volume of energy intake = 1/2, 1, 5/4, 6/4, and 6/4 of the predicted basal
      metabolic rate (PBMR) on days 1-5, respectively. MEASUREMENTS AND MAIN RESULTS:
      Nutritional status by the caloric intake, recommended dietary allowances, PBMR,
      predicted energy expenditure (PEE), anthropometry, and clinical indices were
      evaluated on days 1 and 5. Safety was assessed by the clinical course of disease,
      laboratory findings, and occurrence of complications. Success was determined by
      accomplishment of the PEE target. The early success rate was 94.4% and predicted
      late enteral feeding success accurately (p =.0001). Caloric intake approached
      PBMR the second day (43 +/- 1.7 kcal/kg/day vs. 43.2 +/- 1.1 kcal/kg/day) and PEE
      the fifth day (66.2 +/- 2.7 kcal/kg/day vs. 67.7 +/- 6.4 kcal/kg/day).
      Multivariate stepwise regression analysis showed that poor outcome and a high
      Therapeutic Intervention Scoring System score correlated with failure of EPIGF (p
      <.0001). Patients who succeeded EPIGF had significantly higher myocardial
      ejection (65% vs. 43%; p <.0001) or shortening fractions (34% vs. 20%; p =.0001)
      on day 1 than those who failed. Patients tolerated EPIGF well; 9.9% developed
      nosocomial pneumonia, 5.6% developed diarrhea, and 8.5% needed treatment with
      cisapride because of a delay of gastric emptying. The mortality rate (5.6%) was
      different between initial and final success and failure groups (p <.0001) and was
      lower than predicted by the admission severity scores (12% +/- 2%). CONCLUSIONS:
      This study showed that increases of caloric intake during the acute phase of a
      critical illness are well tolerated and may approach PBMR by the second day and
      PEE by the fourth day in critically ill children. Caloric intake lower than PBMR
      is associated with higher mortality and morbidity rates.

PMID- 12797867
TI  - Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc
      degeneration: biochemical rationale and case report.
AB  - BACKGROUND: Glucosamine and chondroitin sulfate preparations are widely used as
      food supplements against osteoarthritis, but critics are skeptical about their
      efficacy, because of the lack of convincing clinical trials and a reasonable
      scientific rationale for the use of these nutraceuticals. Most trials were on
      osteoarthritis of the knee, while virtually no documentation exists on spinal
      disc degeneration. The purpose of this article is to highlight the potential of
      these food additives against cartilage degeneration in general, and against
      symptomatic spinal disc degeneration in particular, as is illustrated by a case
      report. The water content of the intervertebral disc is a reliable measure of its
      degeneration/ regeneration status, and can be objectively determined by Magnetic
      Resonance Imaging (MRI) signals. CASE PRESENTATION: Oral intake of glucosamine
      and chondroitin sulfate for two years associated with disk recovery (brightening
      of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a
      biochemical explanation for the possible efficacy of these nutraceuticals. They
      are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and
      inhibit the breakdown of their extracellular matrix proteoglycans. CONCLUSION:
      The case suggests that long-term glucosamine and chondroitin sulfate intake may
      counteract symptomatic spinal disc degeneration, particularly at an early stage.
      However, definite proof requires well-conducted clinical trials with these food
      supplements, in which disc de-/regeneration can be objectively determined by MRI.
      A number of biochemical reasons (that mechanistically need to be further
      resolved) explain why these agents may have cartilage structure- and symptom
      modifying effects, suggesting their therapeutic efficacy against osteoarthritis
      in general.

PMID- 12797870
TI  - Magnetic phrenic nerve stimulation to assess diaphragm function in children
      following liver transplantation.
AB  - BACKGROUND: An accurate and practical test of diaphragm function in children in
      the intensive care unit is desirable. Diaphragm dysfunction can occur after liver
      transplantation and may be a contributory factor in the respiratory complications
      after the procedure. OBJECTIVE: Our aim was to assess if magnetic stimulation
      (MS) of the phrenic nerves could be used to assess diaphragm strength in children
      receiving intensive care. SETTING: Pediatric intensive care unit. PATIENTS: Eight
      supine, ventilated, sedated children (mean age, 7.3; range, 0.6-15 yrs) were
      studied within 12 hrs of liver transplantation. INTERVENTIONS: MS was performed
      using either 90-mm double circular coils or 43-mm figure of eight coils placed
      over the phrenic nerves on the anterior aspect of the neck. Measurements: The
      produced diaphragm force was assessed by measuring the transdiaphragmatic
      pressure (Pdi) with balloons in the mid-esophagus and stomach. During MS, the
      endotracheal tube was briefly occluded by using a pneumatic valve. MAIN RESULTS:
      Supramaximal diaphragm force responses were obtained in all subjects; mean Pdi,
      7.8 (sd, 3.1) cmH(2)O for left, 5.2 (sd, 3.4) cmH(2)O for right, and 14.8 (sd,
      9.2) cmH(2)O for bilateral stimulation. Bland and Altman analysis indicated close
      agreement between esophageal and airway pressure during MS (mean difference, 
      0.76 [sd, 0.99] cmH(2)O for left stimulation, 0.81 [sd, 1.25] cmH(2)O for right
      stimulation, and -0.63 [sd, 1.55] cmH(2)O for bilateral stimulation). In three
      children, there was a >50% difference between the Pdi generated after left and
      right unilateral MS and the results of MS indicated complete right hemidiaphragm
      paralysis in one child. CONCLUSION: MS of the phrenic nerves provides a practical
      technique for assessing diaphragm function in children receiving intensive care.
      Measurement of airway pressure during MS may provide a noninvasive technique for
      assessing diaphragm strength when the use of balloon catheters is
      contraindicated.

PMID- 12797872
TI  - Intraosseous infusion and pulmonary fat embolism.
AB  - OBJECTIVES: To determine the incidence of pulmonary fat embolism after the
      intraosseous (IO) infusion of normal saline and drugs and to determine whether
      pulmonary capillary blood is a predictor of lung fat embolism. DESIGN: A
      randomized, prospective, animal study. SETTING: Animal research laboratory of a
      university hospital. SUBJECTS: Twenty-eight mixed breed piglets (average weight
      30.9 kg). Interventions and Methods: Animals were anesthetized, intubated,
      mechanically ventilated, and instrumented. IO needles were placed in the tibial
      bone. Animals were assigned to one of four groups: Group 1 received fluid (20
      mL/kg) under 300 mm Hg pressure (n = 6); group 2 received fluid (20 mL/kg) at
      free flow under gravity (n = 6); group 3 received 100 mL of fluid over 20 mins (n
      = 8); and group 4 received 100 mL of fluid over 7 mins (n = 8). MEASUREMENTS AND
      MAIN RESULTS: Buffy coat samples were obtained from pulmonary arterial catheter
      in the occluded position at baseline, after IO needle placement, and at the end
      of infusion. Lung specimens (both upper and lower lobes) were obtained at the end
      of the infusion. Specimens were stained with oil red O and graded for fat emboli
      by a pathologist blinded to experimental conditions. Fat emboli (one to three
      emboli per high power field) were found in about 30% of the lung specimens. The
      difference in number of fat emboli between groups was not statistically
      significant. Buffy coat stains yielded fat emboli, which were distributed
      sporadically in all groups. CONCLUSION: Fat embolism is common; however, the
      method of IO fluid administration does not influence the number of emboli. Our
      study therefore implies that the risk of fat embolization is of concern, but its
      clinical relevance is unclear. Until the clinical significance of pulmonary fat
      emboli and the prevalence of fat emboli syndrome are delineated more precisely,
      the IO route is an effective but not necessarily safe route for delivery of
      fluids and drugs.

PMID- 12797871
TI  - Frequency of change of ventilator circuit in premature infants: Impact on
      ventilator-associated pneumonia.
AB  - OBJECTIVE: Ventilator-associated pneumonia (VAP) is associated with substantial
      mortality. The frequency of changing the ventilator circuit (VC) might influence
      the occurrence rate of VAP. In premature infants receiving ventilatory support,
      the question regarding the frequency of changing VC is as yet unsettled. DESIGN:
      A prospective, randomized, and controlled trial in 60 premature neonates
      receiving ventilatory support. INTERVENTIONS: We investigated the impact of two
      VC change regimens on VAP in premature infants, either every 24 hrs or every 72
      hrs. In each patient, the humidifier, inspiratory tube, and expiratory tube were
      changed and cultured at the assigned intervals along with cultures of tracheal
      aspirates. Blood cultures were obtained whenever there was clinical evidence of
      pneumonia or sepsis. MEASUREMENTS AND MAIN RESULTS: The two study groups did not
      differ significantly in gestational age, birth weight, gender, duration of
      mechanical ventilatory support, surfactant therapy, duration of hospitalization,
      mortality rate, rate of bloodstream infection, or rate of colonization of
      tracheal aspirate, humidifier, and expiratory tube by microbes. The inspiratory
      tube was significantly less colonized in the 72-hr group as compared to the 24-hr
      group (p <.05). The rate of VAP per 1000 ventilator days was not higher in the 72
      hr group, compared with the 24-hr group (23.3 vs. 37.7; not significant).
      Switching from a 24-hr to a 72-hr change policy would save our neonatal intensive
      care unit a yearly sum of $14,000 (US). CONCLUSIONS: Extending the VC-change
      interval in premature infants from 24 hrs to 72 hrs is safe and cost-effective.

PMID- 12797873
TI  - In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic
      balloon pumping.
AB  - OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic
      balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the
      pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research
      laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart
      circulation and two different aortas with compliances comparable to those of the
      pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made
      at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and
      with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL).
      MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending
      aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic
      pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07
      mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg)
      and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to
      shock, IABP resulted in significant increases in coronary arterial and
      brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow
      significantly increased only in the less-compliant aorta. CONCLUSIONS: In a
      laboratory model of pediatric left heart circulation, IABP results in diastolic
      augmentation, afterload reduction, and improved hemodynamics, even in aortas of
      greater compliance.

PMID- 12797874
TI  - Childhood morbidity after severe traumatic brain injury: Increased detection with
      the Multiattribute Health Status Classification.
AB  - OBJECTIVES: Study 1: To determine the interrater agreement on the Multiattribute
      Health Status Classification (MAHSC) for brain-injured children. Study 2: To
      determine the outcome of severe childhood traumatic brain injury (TBI) by
      comparing three measures: MAHSC, Functional Independence Measures (FIM/WeeFIM),
      and the Glasgow Outcome Scale. Designs: Study 1: Clinic recruitment of parents of
      patients. Study 2: Surveillance follow-up of an inception cohort. Settings: Study
      1: The Brain Injury Clinic, Glenrose Rehabilitation Hospital, Edmonton, Canada.
      Study 2: Pediatric Intensive Care Unit, University of Alberta Hospital. PATIENTS:
      Study 1: Two physiatrists and parents of 50 children (5-18 yrs, 54% boys)
      independently completed the survey. Study 2: From a cohort of 51 patients (3-17
      yrs, 69% boys, 6 deaths) consecutively admitted to the pediatric intensive care
      unit in 1995 and 1996 with severe TBI (Glasgow Coma Score </= 8 within the first
      24 hrs postinjury), parents of all survivors (71% boys) completed outcome
      measures at 6-12 months postinjury. MEASUREMENTS AND MAIN RESULTS: Study 1: The
      interrater agreement exceeded 70% for attributes of sensation, mobility,
      cognition, self-care, and general health. Study 2: Of 45 survivors, 34 (76%) had
      a "good recovery" on the Glasgow Outcome Scale, 16 (36%) had normal scores on the
      FIM/WeeFIM, and only 8 (18%) had normal attributes on the MAHSC. Correlations of
      measures were Glasgow Outcome Scale and MAHSC, -.73; Glasgow Outcome Scale and
      FIM/WeeFIM,.64; and MAHSC and FIM/WeeFIM, -.63. Sensitivity and specificity from
      acute injury predictors for the Glasgow Outcome Scale were 88% and 91%,
      respectively; for MAHSC 75% and 70%; and for FIM/WeeFIM 63% and 75%. CONCLUSIONS:
      The MAHSC has a high interrater reliability after brain injury and is a useful
      parent-report surveillance tool to audit outcome after severe TBI. It identified
      problems not addressed by the Glasgow Outcome Scale or FIM/WeeFIM. Most children
      with severe TBI have adverse outcomes.

PMID- 12797875
TI  - Acute asthma.
AB  - OBJECTIVE: Asthma is the most common medical emergency in children. It is
      associated with significant morbidity and mortality rates and poses a tremendous
      societal burden worldwide. Management of the acute attack involves a stepwise
      approach that includes beta-agonist and steroid therapy, the mainstay of
      emergency treatment. Most patients will respond to this regime and can be
      discharged from the emergency department. Failure to respond to treatment
      necessitates hospital admission and sometimes admission to the intensive care
      unit (ICU). Management in the ICU involves intensification of pharmacologic
      therapy, including nonstandard therapies, in an attempt to avoid intubation and
      ventilation. When needed, mechanical ventilatory support can be rendered fairly
      safe with little morbidity if the likely cardiorespiratory physiologic
      derangements are appreciated and if appropriate ventilatory strategies are used.
      In the past two decades, the availability of newer potent medications and changes
      in approach to monitoring and ventilatory strategies have resulted in a decrease
      in ICU morbidity and mortality rates. Research endeavors are presently underway
      to further characterize the underlying mechanisms of the disease and are likely
      to lead to novel therapies. This article reviews the approach to management of
      acute severe asthma.

PMID- 12797876
TI  - Pediatric noninvasive positive pressure ventilation.
AB  - OBJECTIVE: To review the clinical use of noninvasive positive pressure
      ventilation (NPPV) in both acute hypoxic and hypercarbic forms of pediatric
      respiratory failure, including its mechanism of action and implementation. DATA
      SOURCES: Studies were identified through a MEDLINE search using respiratory
      failure, pediatrics, noninvasive ventilation, and mechanical ventilation as key
      words. STUDY SELECTION: All original studies, including case reports, relating to
      the use of noninvasive positive pressure in pediatric respiratory failure were
      included. Because of the paucity of published literature on pediatric NPPV, no
      study was excluded. DATA EXTRACTION: Study design, numbers and diagnoses of
      patients, types of noninvasive ventilator, ventilator modes, outcome measures,
      and complications were extracted and compiled. DATA SYNTHESIS: For acute hypoxic
      respiratory failure, all the studies reported improvement in oxygenation indices
      and avoidance of endotracheal intubation. The average duration of NPPV therapy
      before noticeable clinical improvement was 3 hrs in most studies, and NPPV was
      applied continuously for 72 hrs before resolution of acute respiratory distress.
      In patients with acute hypercarbic respiratory failure, application of NPPV
      resulted in reduction of work of breathing, reduction in CO(2) tension, and
      increased serum bicarbonate and pH. These patients are older than patients in the
      acute hypoxic respiratory failure group and, in addition to improved blood gas
      indices, they reported improvement in subjective symptoms of dyspnea. Improvement
      in gas exchange abnormalities and subjective symptoms occurred within the same
      time span (the first 3 hrs) as in the acute hypoxic respiratory failure group.
      However, use of noninvasive techniques in patients with acute hypercarbic
      respiratory failure continued after resolution of acute symptoms. Complications
      related to protracted use of NPPV were common in this group. CONCLUSIONS: NPPV
      has limited benefits in a group of carefully selected pediatric patients with
      acute hypoxic and hypercarbic forms of respiratory failure. The routine use of
      this technique in pediatric respiratory failure needs to be studied in randomized
      controlled trials and better-defined patient subsets.

PMID- 12797877
TI  - The costs associated with nosocomial bloodstream infections in the pediatric
      intensive care unit.
AB  - OBJECTIVE: To assess the operational and subsidiary costs and length of stay
      (LOS) attributable to nosocomial bloodstream infections (BSI) in a pediatric
      intensive care unit (PICU). DESIGN: Matched case-control study. SETTING: Sixteen
      bed PICU in a 250-bed tertiary-care pediatric hospital. PATIENTS: Cases with BSI
      were prospectively identified from PICU patients who developed a nosocomial BSI
      from August 1996 to July 1998. Controls were PICU patients who were matched for
      age, severity of illness, diagnosis, and admission date who did not develop a
      nosocomial BSI. RESULTS: A total of 38 cases and 38 controls form the basis for
      this study. The cases and controls were similar with respect to the matching
      criteria. In addition, the cases and controls did not differ with respect to
      demographic characteristics or PICU survival. There was a trend toward increased
      hospital mortality among cases (23.7% vs. 10.5%, p =.084). Significant
      differences were encountered in the utilization of PICU therapeutic modalities.
      Cases were significantly less likely to be managed care plan enrollees (36.8% vs.
      60.5%, p =.043). Total operational and subsidiary costs for radiology, pharmacy,
      and laboratory services were significantly higher for cases than controls
      ($78,272 vs. $35,005, $3,622 vs. $1,432, $8,635 vs. $4,630, and $8,648 vs.
      $3,971, respectively; all p <.001). The PICU and hospital LOS were significantly
      higher for cases than controls (19.3 vs. 4.6 days for PICU and 46.7 vs. 24.4 days
      for hospital; both p <.001). The operational costs attributable to nosocomial
      infection were $46,133. Radiology, pharmacy, and laboratory costs attributable to
      nosocomial infection were $2,364, $4,691, and $5,156, respectively. The PICU and
      hospital LOS attributable to a nosocomial BSI were 14.6 days and 21.1 days,
      respectively. The attributable mortality rate was 13.1%. CONCLUSIONS: The costs
      and LOS associated with nosocomial BSI in patients admitted to the PICU were
      significantly higher than controls.

PMID- 12797878
TI  - Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering
      from heparin-induced thrombocytopenia.
AB  - OBJECTIVE: Despite controversy about whether peripheral and central venous
      catheters should be locked with heparin to prevent catheter-associated clotting,
      the practice is widespread. We describe a severe side effect of the practice: a
      case of heparin-induced thrombocytopenia occurring with catheter flushes using
      unfractionated heparin (UFH) in a 10-month-old boy successfully treated with
      danaparoid. Patient: A preterm-born patient (33 wks gestational age, birth weight
      1200 g) suffering from VACTERL syndrome was repeatedly treated with UFH in the
      context of several invasive procedures. On day 310 of age, a central venous
      catheter was inserted to provide total parenteral nutrition. The central catheter
      was flushed with a continuous infusion of UFH at 100 U/day, and a decrease in
      platelet counts from 150,000/&mgr;L (on day 310 of age) to 45,000/&mgr;L (on day
      319 of age) was observed. Clinically suspected heparin-induced thrombocytopenia
      (HIT) was serologically confirmed by demonstrating HIT antibodies with platelet
      factor 4/heparin complex specificity. Main Result: Catheter flushing was switched
      to low-dose danaparoid sodium as a continuous infusion at 15 anti-factor Xa units
      per day. Two days later, platelet counts recovered. Neither catheter thrombosis
      nor systemic thromboembolic complications occurred during the follow up period.
      CONCLUSIONS: Even continuous infusion of low-dose heparin to provide patency of
      central venous port catheters may trigger the primary immune response of HIT. Low
      dose danaparoid sodium, a heparinoid, can prevent in-catheter thrombus formation
      and allows normalization of platelet counts in acute HIT.

PMID- 12797879
TI  - Hyperammonemic coma caused by Providencia rettgeri infection in a child with
      prune belly syndrome.
AB  - OBJECTIVE: To report a case of hyperammonemic encephalopathy in the absence of
      liver disease caused by a urinary tract infection with a previously unreported
      organism. DESIGN: Case report. SETTING: Pediatric intensive care unit. Patient:
      Critically ill child who presented with hyperammonemic coma. INTERVENTION:
      Bladder drainage and antimicrobial therapy for the urinary tract infection.
      Measurements: Rapid resolution of the hyperammonemia. MAIN RESULTS: Rapid
      improvement in the patient's neurologic status and a return to his baseline
      function without neurologic deficit. CONCLUSIONS: Patients with abnormal urinary
      collecting systems who present with altered mental status should have a serum
      ammonia concentration sent as part of the initial evaluation. We have added
      Providencia species to the list of documented causative organisms in this rare
      association between urinary tract infections and hyperammonemia.

PMID- 12797880
TI  - Comparison of resource utilization and outcome between pediatric and adult
      intensive care unit patients.
AB  - OBJECTIVE: To compare resource utilization and outcomes between cohorts of
      pediatric and adult intensive care unit (ICU) patients from a single institution.
      DESIGN: Prospective, observational cohort study. SETTING: A large, urban,
      tertiary care medical center. PATIENTS: A total of 780 patients consecutively
      admitted to the pediatric ICU, adult medical ICU, and adult surgical ICU.
      MEASUREMENTS AND MAIN RESULTS: ICU, hospital and 6-month survivals and hospital
      costs from index ICU admission. Predicted mortality by Pediatric Risk of
      Mortality III and Acute Physiology and Chronic Health Evaluation II. Health
      status at 6 months from index ICU admission. Pediatric patients had lower ICU
      (7.8% vs. 13.7%; p =.01), hospital (10.1% vs. 16.9%; p =.009), and 6-month (16.2%
      vs. 29.2%; p <.001) mortalities compared with adult patients. Adult patients had
      significantly lower probability of survival for 6 months from initial ICU
      admission compared with pediatric patients. The difference in survival was
      primarily accounted for by adult and pediatric medical patients. No differences
      could be observed between pediatric and adult ICU patients for mean hospital
      costs ($33,316 +/- $48,467 vs. $32,877 +/- $46,411; p =.92). Pediatric and adult
      patients incurred increasing costs with increasing risks of mortality. More than
      50% of pediatric patients had a risk of mortality <0.5% compared with 1.2% of
      adult patients, but there was no difference in the mean use of ICU-specific
      interventions. CONCLUSIONS: Pediatric critical care patients have better short
      term and longer-term survival compared with adult patients. The difference in
      survival is accounted for by the lower survival of adult medical patients.
      Despite the survival differences, pediatric and adult ICU patients incur similar
      hospital costs, and the proportions of patients who receive active ICU
      interventions are similar.

PMID- 12797881
TI  - Effort and work of breathing in neonates during assisted patient-triggered
      ventilation.
AB  - OBJECTIVE: This study compares patient-ventilator synchrony, work of breathing
      and patient effort in neonates during different modes of patient-triggered
      ventilation. DESIGN: Clinically stable neonates received intermittent mandatory
      ventilation (IMV), synchronized intermittent mandatory ventilation (SIMV),
      pressure assist/control ventilation (A/C), and pressure support ventilation (PSV)
      in a random order for 20 mins. With each mode patient-ventilator synchrony, work
      of breathing, and patient effort were evaluated. SETTING: Neonatal level III
      intensive care unit of a university hospital. Measurements and RESULTS: Seven
      clinically stable neonates (31.4 +/- 2 wks gestation, weighing 1.49 +/- 0.38 kg)
      were randomly ventilated with the above four modes using a Bird VIP ventilator.
      Esophageal pressure, airway pressure, and flow were measured using a CP-100
      neonatal monitor (Bicore). Data for five consecutive breaths in each mode were
      analyzed. Patient effort and work of breathing differed significantly among modes
      of ventilation. The inspiratory pressure time product was least with A/C (0.54 +/
      0.29 cm H(2)O.sec) and increased with PSV (0.60 +/- 0.39 cm H(2)O.sec), SIMV
      (1.46 +/- 0.55 cm H(2)O.sec), and IMV (2.74 +/- 1.05 cm H(2)O.sec) (p <.05). A
      similar trend was observed for work of breathing, with work least during A/C
      (0.07 +/- 0.04 joules per liter [J/L]), followed by PSV (0.17 +/- 0.14 J/L), SIMV
      (0.33 +/- 0.13 J/L), and IMV (0.41 +/- 0.16 J/L) (p <.05). Marked dyssynchrony
      between patient-initiated and ventilator-initiated inspiration occurred only
      during IMV. CONCLUSION: Asynchrony can be avoided by the use of assisted, patient
      triggered modes of ventilation and, of the available modes, pressure A/C results
      in the least effort and work of breathing for clinically stable neonates.

PMID- 12797882
TI  - What happens when chest tubes are removed in children?
AB  - OBJECTIVE: To evaluate the incidence, onset, and severity of complications in
      children after chest tube removal. DESIGN: A prospective evaluation of patients.
      SETTING: Pediatric intensive care unit in a tertiary care university hospital.
      PATIENTS: One hundred and one consecutive children requiring intraoperative
      placement of chest tubes for cardiac or noncardiac thoracic surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 120 chest tubes placed
      in 101 patients, 16 were associated with positive findings after removal. Of
      these 16, only six required changes in management, and only two were serious
      complications. There was no association of complications with duration of chest
      tube placement. Children who developed complications were younger. All serious
      complications were immediately apparent after chest tube removal. CONCLUSION:
      Serious complications of chest tube removal in children are very uncommon and in
      this series were immediately apparent.

PMID- 12797883
TI  - A comparison of propofol and ketamine/midazolam for intravenous sedation of
      children.
AB  - OBJECTIVE: To compare ketamine and propofol sedation in children undergoing
      diagnostic and therapeutic procedures. DESIGN: Retrospective study. SETTING: A
      six-bed pediatric intensive care unit and a pediatric hematology oncology clinic.
      PATIENTS: From 1996 to 1998, 405 procedures were performed on patients between 1
      month and 22 yrs of age. INTERVENTIONS: All patients but one were sedated
      intravenously with either propofol or ketamine; those who received ketamine also
      received midazolam and either atropine or glycopyrrolate. Vital signs were
      monitored continuously. Procedures included bone marrow biopsies, lumbar
      punctures, esophagoduodenoscopies, colonoscopies, and other miscellaneous
      procedures. A pediatric intensivist performed all sedations. MEASUREMENTS AND
      MAIN RESULTS: Two hundred sixty-one procedures were conducted with propofol and
      144 with ketamine. The mean time (+/-sd) from administration of the first dose of
      medication until the patient was awake was 36.6 (15.0) mins for the propofol
      group and 69.2 (43.2) mins for the ketamine group. The mean time to awakening was
      significantly longer for the ketamine group, even after adjusting for the length
      of the procedure, American Society of Anesthesiologists score, and setting of
      procedure (inpatient or outpatient; p =.0001). Only one unplanned endotracheal
      intubation in the propofol group and two in the ketamine group occurred. Patients
      were significantly more likely to have airway (p =.01) or hemodynamic (p =.002)
      effects with propofol than with ketamine, although these effects were essentially
      minor in nature. CONCLUSIONS: Both propofol and ketamine provided safe and
      effective sedation for the short, painful procedures performed. Because the
      patients who received propofol awakened almost twice as quickly as the patients
      who received ketamine, the sedation service operated more efficiently when
      propofol was used. The major complication rates for propofol and ketamine were
      small, and the differences between the two groups were not statistically
      significant. We conclude that with proper monitoring, intravenous propofol can be
      used safely and effectively for short procedures in the pediatric setting.

PMID- 12797884
TI  - Amrinone in pediatric refractory septic shock: An open-label pharmacodynamic
      study.
AB  - OBJECTIVE: To investigate the short-term hemodynamic effects of amrinone in
      pediatric patients with refractory septic shock. DESIGN: Open-label, clinical
      trial. SETTING: Pediatric intensive care unit. PATIENTS: Nine patients admitted
      with a diagnosis of septic shock receiving stable doses of vasopressors and
      inotropes. INTERVENTIONS: Pediatric patients with septic shock and a pulmonary
      artery catheter were treated with amrinone in a stepwise fashion at 5, 10, and 15
      &mgr;g/kg/min. MEASUREMENTS AND MAIN RESULTS: Heart rate, blood pressure, cardiac
      index, rate pressure product, systemic vascular resistance index, pulmonary
      vascular resistance, oxygen delivery, and oxygen consumption were measured at
      baseline and 90 mins after each amrinone dose. The addition of amrinone increased
      cardiac index (p <.05) and oxygen delivery (p <.05) without increasing the rate
      pressure product. Decreases were observed in systemic vascular resistance index
      (p <.05) and pulmonary vascular resistance (p <.05). No significant changes were
      seen in heart rate, blood pressure, or oxygen consumption. CONCLUSIONS: In this
      short-term, dose-response study in children with refractory septic shock,
      amrinone improved cardiac index and oxygen delivery in pediatric patients with
      refractory septic shock without increasing myocardial work.

PMID- 12797885
TI  - The role of insulin-like growth factor I, growth hormone, and plasma proteins in
      surgical outcome of children with congenital heart disease.
AB  - OBJECTIVE: To evaluate postoperative serum concentrations of growth hormone (GH),
      insulin-like growth factor I (IGF-I), C-reactive protein (CRP), and prealbumin as
      predictors of clinical outcome as defined by the incidence of 30-day
      postoperative mortality, the postoperative length of pediatric intensive care
      unit (PICU) stay, and the risk of postoperative infection in infants of high
      surgical risk undergoing operative correction of congenital cardiac defects.
      DESIGN: Prospective, observational study. SETTING: PICU of a university hospital.
      PATIENTS: A high surgical risk group of 36 children admitted for elective cardiac
      surgery. INTERVENTION: Measures of serum levels of IGF-I, basal GH, prealbumin,
      and CRP. These parameters were followed from the hospital admission until the
      discharge from the PICU at specific time points: preoperative and on the second,
      fifth, and tenth postoperative days. MEASUREMENTS AND MAIN RESULTS: Surgical
      stress response was marked by an increase of GH and CRP levels and a fall in
      prealbumin levels on the second postoperative day. Prealbumin, CRP, and GH
      returned to preoperative levels on average 10 days following surgery; the values
      of IGF-I, which had decreased on the fifth day, remained below those values
      observed before the surgery. Patients whose PICU stay was </= 10 days showed
      significant decreases in GH and CRP serum levels and an increase in IGF-I and
      prealbumin levels on postoperative day 5 compared with the patients who stayed >
      10 days. The sustained high CRP (>/= 8.4 mg/dL, p <.05) and GH (>/= 66 mIU/L, p
      <.03) values on the fifth day were associated with increased mortality in
      contrast with patients in whom the values were returning to preoperative levels.
      CONCLUSIONS: Serial monitoring of serum GH, IGF-I, CRP, and prealbumin levels may
      be useful as a means to a) stratify the acute metabolic response to surgically
      induced injury insult and b) predict clinical outcome as defined by the length of
      stay in the PICU and the likelihood of 30-day survival following open-heart
      surgery in infants.

PMID- 12797886
TI  - Cardiopulmonary bypass surgery does not further increase elevated serum leptin
      concentrations after major surgery.
AB  - OBJECTIVE: The objective of the present study was to examine the impact of major
      heart surgery with cardiopulmonary bypass (CPB) in childhood on serum leptin
      concentrations in relation to plasma cortisol, epinephrine, norepinephrine, and
      insulin. DESIGN: Controlled, prospective study. SETTING: Intensive care unit of a
      university hospital. Patients and INTERVENTIONS: We enrolled 20 pediatric
      patients undergoing open heart surgery and 20 children with major surgery not
      necessitating CPB (surgical control group). Leptin was measured by
      radioimmunoassay, cortisol and insulin were measured by chemiluminescence, and
      epinephrine and norepinephrine were measured by high-pressure liquid
      chromatography. MEASUREMENTS AND MAIN RESULTS: In the CPB group, leptin dropped
      from 0.4 +/- 0.1 preoperatively (mean +/- sem) to 0.2 +/- 0.1 ng/mL
      intraoperatively (p <.05). It increased to 1.6 +/- 0.7 ng/mL 12 hrs after surgery
      (p <.01) and declined thereafter. In the surgical controls, leptin rose from 0.5
      +/- 0.2 ng/mL before surgery to 1.8 +/- 0.8 ng/mL 12 hrs after surgery (p =.001).
      In both groups, plasma cortisol, insulin, and epinephrine significantly increased
      after surgery. There was no relationship between the maximum increase of serum
      leptin and the other hormones. CONCLUSIONS: Patients with CPB surgery and non-CPB
      surgery show a similar increase in serum leptin, indicating that sepsislike
      inflammatory syndrome does not further increase elevated leptin concentrations
      following major surgery. In this complex situation, serum leptin does not appear
      to be merely regulated by its known stimuli and suppressors.

PMID- 12797887
TI  - Superior vena cava syndrome following neonatal cardiac surgery.
AB  - OBJECTIVE: To review the incidence, diagnosis, and management of superior vena
      cava syndrome (SVCS) after surgery for congenital heart disease. DESIGN:
      Retrospective clinical review. All patients were computer registered. Our
      database includes daily follow-up. SETTING: Pediatric cardiac surgery intensive
      care unit in a university hospital. PATIENTS: A total of 1853 consecutive
      pediatric cardiac operations performed in 285 neonates and 1568 older children
      from 1993 to 1999 are reviewed. MEASUREMENTS AND MAIN RESULTS: The diagnosis of
      SVCS was suspected clinically: Color changes and swelling of the upper part of
      the body, confirmed by echo-Doppler, showed no or minimal flow in the superior
      vena cava at the beginning and collateral flow later on. Nine patients developed
      SVCS (0.5%). All the study patients were neonates. The prevalence of SVCS in our
      neonatal patients was 3.15% (nine of 285), with no SVCS in older children.
      Accompanying complications included chylothorax (five), hydrocephalous (four)
      three of whom required ventriculoperitoneal shunt during follow-up. Thrombolytic
      therapy was used in five patients, and thrombectomy was used in one patient. The
      ventilation period ranged from 4 to 46 days (mean 20.1 days), and the length of
      hospital stay ranged from 37 to 120 days (mean 61.3 days). No mortality was
      observed during follow-up. CONCLUSIONS: SVCS is an uncommon, severe complication
      following neonatal cardiac surgery. It may cause chylothorax, hydrocephalus, and
      severe respiratory complications leading to high morbidity. Early diagnosis and
      thrombolytic therapy may prevent the progression of this syndrome to its
      subsequent sequels.

PMID- 12797888
TI  - Hepatic dysfunction after cardiac surgery in children.
AB  - OBJECTIVE: The objective of this study was to analyze the incidence and
      significance of hepatic dysfunction after cardiac surgery in children. DESIGN:
      Prospective, observational study. SETTING: Pediatric intensive care unit of a
      university hospital. PATIENTS: The study consisted of 232 children ranging in age
      from newborn to 17 years with no history of liver disease. MEASUREMENTS AND MAIN
      RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      gammaglutamyltranspeptidase (GGT), alkaline phosphatase, total and conjugated
      bilirubin, blood glucose, urea, creatinine, and coagulation studies were
      determined at admission, at 24 and 48 hrs, and at 7 days. Hepatic dysfunction was
      taken as an ALT of > 100 IU/L or a moderate or high hepatic score. The
      statistical study included bivariate analysis and multivariate logistic
      regression to study the risk factors for hepatic dysfunction. Twenty-one patients
      (9%) showed an ALT > 100 IU/L, and 29.3% had a moderate or high hepatic score. A
      relationship was found between hepatic dysfunction and the type of cardiopathy (D
      transposition of the great arteries and coarctation of the aorta), shock, the
      administration of dopamine or epinephrine, renal insufficiency, the presence of
      pulmonary changes (pulmonary edema, atelectasis, pulmonary hypertension,
      hypoxemia), hematologic disturbances (prothrombin time, kaolin-cephalin time,
      fibrinogen, and platelets), and the need for a greater number of transfusions of
      packed cells, plasma, and platelets. Compared with 7.6% of the rest of the
      patients (p <.001), 38% of patients with an ALT > 100 IU/L died. The hepatic
      score of those patients who died was 4.2 (2.3)-higher than that of the survivors
      at 1.5 (1.8), (p <.001). Shock and renal insufficiency were the factors most
      significantly related to the development of hepatic dysfunction. CONCLUSIONS:
      Hepatic dysfunction is an uncommon complication in children after cardiac
      surgery. This complication is related mainly to hemodynamic disturbances and
      renal insufficiency and is an indicator of poor prognosis.

PMID- 12797889
TI  - Abdominal compartment syndrome in children.
AB  - OBJECTIVE: To investigate the frequency, predisposing factors, clinical
      presentation, and outcome of abdominal compartment syndrome (ACS) in critically
      ill pediatric patients. DESIGN: A prospective study over a 5-yr period. SETTING:
      Pediatric intensive care unit of a tertiary care, university hospital. PATIENTS:
      All patients admitted to the pediatric intensive care unit were screened for the
      presence of ACS and were treated with a uniform protocol. ACS was defined as
      abdominal distention with intra-abdominal pressure (IAP) > 15 mm Hg, accompanied
      by at least two of the following: oliguria or anuria; respiratory decompensation;
      hypotension or shock; metabolic acidosis. MEASUREMENTS AND MAIN RESULTS: Of 1762
      patients admitted over 5 yrs, ten patients (0.6%) had a total of 15 episodes of
      ACS. Of 406 trauma cases, three had ACS (0.7%). Three of the ten patients had
      primary abdominal conditions (mesenteric vein thrombosis, intussusception,
      enterocolitis), three had abdominal surgery (trauma, Kasai operation, esophageal
      perforation and peritonitis), three had primary central nervous system
      involvement, and one had meningococcemia. At laparotomy, bowel ischemia or
      necrosis was found in four episodes of ACS (27%). Mean IAP at diagnosis of ACS
      was 23.9 +/- 3.8 (range 17-31) mm Hg. Physiologic parameters were compared during
      4 hrs before the development of ACS, during ACS, and after abdominal
      decompression. Mean arterial pressure, Pao(2), Pao(2)/Fio(2) ratio, and urinary
      output decreased significantly, whereas Paco(2), peak inspiratory pressures,
      positive end-expiratory pressures, and base deficit increased significantly after
      the development of ACS. After decompressive laparotomy, the condition of the
      patients improved promptly and these variables returned to pre-ACS values.
      Overall mortality rate in this group was 60%. CONCLUSIONS: Although relatively
      infrequent compared with adults, ACS occurs in critically ill children. Timely
      decompression of the abdomen results in uniform improvement, but overall
      mortality is still high. In contrast with adults, children with ACS have diverse
      primary diagnoses, with a significant number of primary extra-abdominal-mainly
      central nervous system-conditions. Ischemia and reperfusion injury appear to be
      the major mechanisms for development of ACS in children. Clinical presentation is
      similar to adults, but children may develop ACS at a lower IAP (as low as 16 mm
      Hg).

PMID- 12797890
TI  - Complications of central venous catheterization in critically ill children.
AB  - OBJECTIVE: Analysis of central venous catheterization complications in different
      access sites with the Seldinger technique. Patients and Methods: A prospective
      study (May 1992 through December 1996) of 308 central venous catheterizations in
      children of different ages in a pediatric intensive care unit. RESULTS: Access
      sites were the subclavian vein (76.3%), femoral vein (20.4%), and jugular vein
      (3.2%). The frequency of catheter placement-related complications was 22%, and
      the frequency of serious catheter placement-related complications was 2.9%
      (pneumothorax 1.9%, hemothorax 1%). Catheter placement-related complications were
      more common in the subclavian than in the femoral vein (chi-square, p =.02) for
      the larger bore catheters (chi-square, p =.01) and for the higher number of
      attempts (Student's t -test, p <.001). Catheter placement-related complications
      were not related to the age, weight, or whether the procedure was performed by
      the staff physician or resident. The overall complication rate for maintenance
      related complications was 36%. Maintenance-related complications were more common
      in younger children (Student's t -test, p =.03). The most frequent maintenance
      related complications were mechanical complications (catheter obstruction and
      central venous thrombosis), and these were higher for femoral access (chi-square,
      p <.01) and for catheters indwelling for a longer period of time. Infection was
      found in 5.8% of patients, mainly due to Staphylococcus epidermidis. Infection
      was not related to the site of venous access or to the length of time the
      catheter was left indwelling. CONCLUSIONS: Central venous catheterization can be
      performed readily in children of all ages with an acceptable degree of risk. The
      immediate complications were more frequent and severe for subclavian vein
      catheterization, and the highest risk factor was the number of attempts at
      catheter insertion. Although the most frequent late complications were
      mechanical, which were higher for the femoral access and long-indwelling
      catheters, femoral catheters can be left indwelling for longer periods if routine
      ultrasound follow-up is performed. Infectious complications were independent of
      the venous access site or the duration of catheterization.

PMID- 12797891
TI  - Pulmonary antioxidant enzyme activity during early development: Effect of
      ventilation.
AB  - OBJECTIVE: To examine the effect of tidal liquid ventilation (TLV) and
      conventional gas ventilation (GV) on the pulmonary antioxidant enzyme (AOE)
      activity in two groups of preterm lambs at 110 and 120 days of gestation and to
      compare these results to age-matched fetal controls. DESIGN: Experimental,
      prospective, randomized, controlled study. SETTING: School of medicine,
      department of physiology. SUBJECTS: Thirty-two premature lambs at 110 days (n =
      16) and 120 days (n = 16) gestation. INTERVENTIONS: Six lambs at 110 and 120 days
      were ventilated with TLV for 4 hrs. Three lambs at 110 days were ventilated with
      GV for 3 hrs, and six lambs at 120 days were ventilated with GV for 4 hrs. Four
      lambs, each at 110 and 120 days, were used as age-matched fetal controls.
      Measurements: Sequential measurements of arterial blood chemistries were
      performed in all groups. Biochemical assays included catalase activity,
      superoxide dismutase activity, and glutathione peroxidase activity. Histologic
      examinations of lung sections from TLV and GV lungs were performed. Main Result:
      Despite vast differences in physiologic outcome, there were fewer differences in
      AOE activity as a function of ventilation (fetal control, GV, and TLV lambs)
      and/or gestational age. There were no significant differences in superoxide
      dismutase and glutathione peroxidase activity as a function of age or
      ventilation. Catalase activity was significantly higher (p <.05) in fetal 120-day
      control lambs (24.8 +/- 1.9 units/mg protein) relative to the 110-day control
      lambs (14.3 +/- 1.7 units/mg protein). Catalase activity significantly (p <.05)
      decreased in both GV and TLV 120 day lambs compared with fetal controls; yet, in
      the 110-day gestational lambs, there were no significant differences in enzyme
      level as a function of ventilation. Thus, an age-specific response to ventilation
      was evident for catalase activity. CONCLUSION: The present data demonstrate
      several developmental differences in AOE activity. The lack of ventilation effect
      in AOE activity, in view of the big difference in physiologic and inflammatory
      outcomes, suggests that mechanisms associated with free radicals do not underlie
      the response to different modes of ventilation.

PMID- 12797892
TI  - The use of intratracheal pulmonary ventilation and partial liquid ventilation in
      newborn piglets with meconium aspiration syndrome.
AB  - OBJECTIVE: To determine whether intratracheal pulmonary ventilation (ITPV)
      combined with partial liquid ventilation (PLV) improves oxygenation and
      ventilation at lower mean airway and peak inspiratory pressures when compared
      with conventional mechanical ventilation in a piglet model of meconium aspiration
      syndrome. DESIGN: Prospective, randomized, interventional study. SETTING: Animal
      Research Laboratory at the Children's National Medical Center, Washington, DC.
      SUBJECTS: Twenty newborn piglets, 1 to 2 wks of age, 1.8-2.8 kg in weight.
      INTERVENTION: The animals were anesthetized, paralyzed, and intubated with a 4.0
      mm (internal diameter) endotracheal tube via a tracheostomy and were ventilated.
      Catheters were placed in the femoral artery and vein. Seven milliliters per
      kilogram of 20% human meconium was insufflated into the lungs over 30 mins.
      Dynamic pulmonary compliance was measured before and after instillation of
      meconium. Animals were ventilated to maintain arterial blood gases in a normal
      range, that is, pH = 7.35-7.45, Paco(2) = 40-45 torr (5.3-6.0 kPa), and Pao(2) =
      70-90 torr (9.3-12.0 kPa). Ventilator settings were increased as needed to a
      maximum setting of Fio(2) = 1.0, peak inspiratory pressure (PIP) = 40 cm H(2)O,
      positive end-expiratory pressure = 5 cm H(2)O, and intermittent mandatory
      ventilation = 60 bpm. After a period of stabilization, 30 mL/kg of perflubron
      (Liquivent; Alliance Pharmaceutical Corp., San Diego, CA) was given
      intratracheally over 30 mins and the animals were randomized to either ITPV or
      control group. Measurements and RESULTS: Arterial blood gases were taken every 30
      mins, and ventilatory settings were adjusted to achieve the targeted blood gas
      parameters. The animals' temperature, arterial blood pressure, heart rate, and
      oxygen saturation were monitored continuously. There was a significant decrease
      in the dynamic pulmonary compliance measurements in both groups immediately after
      meconium instillation. Compliance measurements after meconium instillation were
      similar in both groups (0.67 +/- 0.23 mL/cm H(2)O/kg ITPV; 0.88 +/- 0.46 mL/cm
      H(2)O/kg conventional, p =.17), indicating a similar degree of injury before the
      administration of perflubron. PIP and mean airway pressures were not
      significantly different at baseline; however, there was significant difference in
      PIP at 0, 2, and 4 hrs after administration of perflubron (p <.05). The maximum
      PIP and mean airway pressure were seen in both groups after meconium instillation
      before perflubron administration, with a mean PIP of 29.0 +/- 4.6 cm H(2)O in
      ITPV and 28.8 +/- 2.1 cm H(2)O in control. Mean airway pressure was significantly
      different between the two groups at 0, 1, 2, 3, and 4 hrs after perflubron
      administration. Lung pathology showed a uniform distribution of meconium in
      animals of both groups. The alveolar spaces were relatively clear of meconium and
      appeared to be well preserved. CONCLUSION: The results of this study indicate
      that ITPV combined with PLV allows for effective ventilation and oxygenation in
      piglets with meconium aspiration syndrome at lower mean airway pressure and PIP
      compared with conventional ventilation combined with PLV.

PMID- 12797893
TI  - Fetal exposure to magnesium chloride-adenosine triphosphate (MgCl2-ATP) results
      in alterations in cerebral blood flow and a metabolic acidosis.
AB  - OBJECTIVE: Magnesium chloride-adenosine triphosphate (MgCl(2)-ATP), advocated as
      an adjunct treatment in shock resuscitation, might be useful for pregnant women
      who develop hypovolemia secondary to conditions such as placental abruption. The
      effects of this treatment on the fetus, however, have never been investigated.
      This study determined the direct, acute effects of MgCl(2)-ATP on fetal organ
      blood flow, hemodynamic measurements, and metabolic parameters before and after
      maternal hemorrhage. DESIGN: Experimental, randomized, nonblinded, control study.
      SETTING: Animal laboratory at a university research facility. SUBJECTS: This
      study was performed on 11 chronically instrumented, 123-day gestational age,
      pregnant ewes (term = 147 days) and their fetuses. INTERVENTIONS: Ewes were
      randomly allocated to either experimental (Expt, n = 5) or control (Cntl, n = 6)
      groups. After a 60-min baseline period, Expt fetuses received a 60-min iv
      infusion of MgCl(2)-ATP (150 &mgr;mole/hr each of MgCl(2) and ATP; at 3 mL/hr),
      and Cntl fetuses received an equivalent volume of 0.9% NaCl. After this infusion
      only period, the infusion was continued, and ewes were intermittently bled over 1
      hr for a total blood loss of 20 mL/kg (hemorrhage-plus-infusion period). After
      this, the infusions were continued, and ewes and fetuses were monitored for 1
      additional hr (posthemorrhage period). Measurements: At the end of all periods,
      fetal and maternal blood pressures, blood gases, oxygen saturation, hemoglobin,
      serum electrolytes, and serum glucose concentrations were measured. At the end of
      the baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal organ
      blood flows were determined using a fluorescent microsphere technique.
      Nonparametric statistics were used for comparisons (2-tailed, p </=.05). MAIN
      RESULTS: Maternal hemorrhage caused maternal hypotension, resulting in a decrease
      in fetal oxygen content and an increase in fetal hemoglobin and glucose
      concentrations. The changes were similar in both groups. In both groups, a
      progressive fetal metabolic acidosis developed during the hemorrhage period and
      it continued through the posthemorrhage period. This metabolic acidosis was more
      severe in the Expt fetuses and appeared to have started during the infusion-only
      period. There were no fetal deaths in either group. In the Cntl fetuses, there
      were increases from baseline after the hemorrhage-plus-infusion period in fetal
      adrenal (71%), brain (89%), and thymus (18%) blood flow and a decrease in muscle
      (-28%) blood flow. In the Expt fetuses, there were increases during the infusion
      only period in adrenal (332%), myocardial (142%), and pancreatic (219%) blood
      flow and decreases in kidney (-25%) and skin (-75%) blood flow. These changes
      persisted during the hemorrhage-plus-infusion period. Most strikingly, regional
      cerebral blood flow in the Expt fetuses did not increase from baseline in any of
      the 10 brain areas sampled during the infusion-only period or following maternal
      hemorrhage. In Cntl fetuses, however, there was increase in blood flow in all 10
      brain areas sampled following maternal hemorrhage. CONCLUSIONS: In healthy
      fetuses, direct MgCl(2)-ATP exposure caused metabolic acidosis and a
      redistribution of cardiac output to different organs. When the MgCl(2)-ATP
      fetuses were then subject to the effects of maternal hemorrhage, the expected
      increase in cerebral blood flow was not observed. Although an earlier study
      suggests that ATP may be beneficial to stressed fetuses when administered to
      mothers in labor, the direct effect of MgCl(2)-ATP appears to be potentially
      harmful by producing an acidosis and altering the normal fetal cerebral blood
      flow response to maternal hemorrhage.

PMID- 12797894
TI  - Functional residual capacity determines the effect of inhaled nitric oxide on
      intrapulmonary shunt and gas exchange in a piglet model of lung injury.
AB  - OBJECTIVE: Hypoxemic respiratory failure in the newborn infant due to severe
      parenchymal lung disease is caused by large, intrapulmonary, right-to-left
      shunting. Nitric oxide (NO) has been shown to reduce shunting and improve
      oxygenation-however inconsistently-in a variety of neonatal lung diseases such as
      meconium aspiration pneumonitis, bacterial pneumonia, surfactant deficiency, and
      others. The aim of this study was to determine whether lung expansion, as
      determined by functional residual capacity (FRC), by means of increasing levels
      for positive end-expiratory pressure (PEEP) would augment the effect of NO on
      reducing right-to-left shunting. DESIGN: Prospective, randomized, controlled,
      animal laboratory investigation. SETTING: University laboratory. SUBJECTS:
      Newborn piglets (n = 8), anesthetized and mechanically ventilated. INTERVENTIONS:
      The piglets were made surfactant deficient by repeated airway lavage aiming at a
      Pao(2) of 45 mm Hg (6 kPa) while using an Fio(2) of.6. Two hours after lavage,
      different PEEP levels of 4, 6, 8, 10, and 12 cm H(2)O (.4,.6,.8, 1.0, and 1.2
      kPa) were used in a random order, keeping tidal volumes strictly at 8 mL/kg. All
      measurements were made with or without NO at 10 ppm in a random order, thus each
      animal served as its own control. A nitrogen washout method was used to measure
      FRC and alveolar volume, in addition to tidal volume, and compliance and
      resistance of the respiratory system. MEASUREMENTS AND MAIN RESULTS: Improvement
      in oxygenation and reduction of right-to-left shunting was optimal while
      achieving FRC values comparable with those values before airway lavage
      (approximately 25 mL/kg) while using PEEP levels of 6 to 8 cm H(2)O (.6 to.8
      kPa). Further lung expansion did not augment the NO effect. In addition, alveolar
      volume and compliance of the respiratory system were positively influenced by NO,
      resulting in a small, but significant, decrease in Paco(2). CONCLUSION: We
      conclude that improvement in oxygenation by the administration of inhaled NO can
      be optimized by achieving FRC values comparable with those of the undiseased lung
      before airway lavage.

PMID- 12797895
TI  - Cerebral blood flow during partial liquid ventilation in surfactant-deficient
      lungs under varying ventilation strategies.
AB  - OBJECTIVE: To test the hypothesis that cerebral and other regional organ blood
      flow would be maintained during partial liquid ventilation (PLV) in an animal
      model of acute lung injury during different ventilation strategies. DESIGN: A
      prospective, randomized study. SETTING: Animal research facility. SUBJECTS:
      Sixteen piglets, 2 to 4 wks of age. INTERVENTIONS: Severe lung injury was induced
      in infant piglets by repeated saline lavage and high tidal volume ventilation.
      Animals were then randomized to either conventional volume-controlled ventilation
      or PLV. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was determined in both
      groups using radiolabeled microspheres under four conditions: high mean airway
      pressure, Paw; high Paco(2), high Paw; normal Paco(2); low Paw, high Paco(2); low
      Paw, normal Paco(2). There were no differences in cerebral blood flow during
      conventional ventilation and PLV, regardless of ventilation strategy.
      CONCLUSIONS: These results suggest in an acute lung injury model, PLV does not
      affect cerebral blood flow or other regional organ blood flow over a range of
      airway pressures.

PMID- 12797896
TI  - Meconium aspiration injury: Uncoupling between the in vivo physiologic and in
      vitro inflammatory responses.
AB  - OBJECTIVE: To correlate the in vivo physiologic changes that occur with meconium
      aspiration injury to an associated in vitro cellular response to meconium.
      DESIGN: Experimental, prospective, randomized, controlled study. SETTING:
      University research laboratory. SUBJECTS: Eighteen adult Sprague-Dawley rats with
      meconium aspiration injury. INTERVENTIONS: Rats were given 3 mL/kg of a 25%
      meconium solution and were treated with conventional gas ventilation; nine rats
      were given exogenous surfactant therapy (Survanta, 4 mL/kg), and nine rats were
      not treated (control). Bronchoalveolar lavages were collected for total cell
      counts. Histologic samples also were taken for analysis. In addition, the in
      vitro effect of meconium on granulocytic elastase release from human neutrophils
      was determined. MEASUREMENTS AND MAIN RESULTS: Meconium caused significant
      morbidity in vivo, including poor oxygenation, elevated Paco(2), diminished
      compliance, and elevated white cell count in the bronchial lavages. Lung white
      cell count was significantly less in the surfactant group (p <.01). Meconium did
      not cause elastase release from human neutrophils in vitro. CONCLUSIONS: This
      study demonstrated uncoupling between in vivo physiologic responses to meconium
      injury in rats and the in vitro effect of meconium on human neutrophils.
      Surfactant therapy alleviated some of the perturbations associated with meconium
      injury, including a reduction in the inflammatory cell count in lung lavages. The
      absence of direct neutrophil activation by meconium suggests the requirement of
      an intermediary in the pathogenesis of meconium aspiration injury.

PMID- 12797897
TI  - Methemoglobinemia: Toxicity of inhaled nitric oxide therapy.
AB  - Elevation in methemoglobin is a known toxicity of inhaled nitric oxide (NO)
      therapy. This article describes two significant episodes of methemoglobinemia.
      These cases illustrate the probable cause and the treatment strategies for the
      potential for delivery of high concentrations of NO, resulting in
      methemoglobinemia with moderate and even low-dose delivered NO. We propose
      mechanisms for this occurrence and means of prevention.

PMID- 12797898
TI  - Interleukin-19 (IL-19) network revisited.

PMID- 12797899
TI  - Effect of the compound L-mimosine in an in vivo model of chronic granuloma
      formation induced by potassium permanganate (KMNO4).
AB  - The plant amino acid L-mimosine has recently been suggested to inhibit cells at a
      regulatory step in late G1 phase before establishment of active DNA replication
      forks. In addition, L-mimosine is an extremely effective inhibitor of DNA
      replication in chromosomes of mammalian nuclei. In this work, the effect of L
      mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40
      saturated crystal solution of potassium permanganate in mice, was studied. Seven
      days afterwards, all mice developed a subcutaneous granulomatous tissue
      indicative of chronic inflammatory response at the site of infection. The
      intraperitoneal administration of L-mimosine (200 microg/dose) to the potassium
      permanganate treated mice for 5 consecutive days (the first at the same time of
      inoculation of the KMnO4), produced a significant decrease in size and weight of
      the granuloma when compared to mice not treated with L-mimosine (controls). In
      addition, in all mice treated with L-mimosine, there was a strong inhibition of
      tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the
      minced granulomas. Interleukin-6 was not detected in the serum of treated and
      untreated mice. These findings show for the first time, that L-mimosine may have
      an anti-inflammatory effect on chronic inflammation and an inhibitory effect on
      tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of
      minced granulomas.

PMID- 12797900
TI  - Prevalence of Borrelia Burgdorferi sensu lato genomospecies and of the human
      granulocytic ehrlichiosis (HGE) agent in Ixodes ricinus ticks collected in the
      area of Monti Lepini, Italy.
AB  - Ticks are obligate hematophagous arthropods that are parasites in every class of
      vertebrates in most regions of the world. They are also considered to be
      important vectors for the transmission of human infectious diseases. In the
      present study we used polymer chain reaction (PCR) amplification analysis to
      determine the prevalence of Borrelia burgdorferi and Ehrlichia phagocytophila,
      the agents of, respectively, Lyme borreliosis and human granulocytic
      ehrlichiosis, among ticks inhabiting the area of Monti Lepini, a wild area
      located in the Latium Region of Italy. A total of 141 I. ricinus ticks (125
      nymphs and 16 adults) were collected in the studied area. Total DNAs were
      extracted from I. ricinus nymphs (pooled in groups of five) and from individual
      adults. The DNA samples were examined for the presence of B. burgdorferi sensu
      lato and E. phagocytophila by PCR using two specific pairs of oligonucleotides
      that specifically amplify distinct DNA regions of the 16S rRNA genes of the two
      species. The prevalence of vectors infected with B. burgdorferi s. l. was 16% in
      pooled nymphs samples, and 12.5% in adult ticks, while E. phagocytophila was
      found only in pooled nymphs samples (8%). Three genomospecies were identified,
      namely Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana, in samples
      found positive for B. burgdorferi s. l. No sample was found positive for Borrelia
      burgdorferi sensu stricto.

PMID- 12797901
TI  - Detection of TT virus in lymph node biopsies of B-cell lymphoma and Hodgkin's
      disease, and its association with EBV infection.
AB  - Human TT virus (TTV) recently isolated from the serum of a patient with post
      transfusion hepatitis does seem to have only hepatopathic effect. The virus can
      also infect the serum, peripheral blood mononuclear cells (PBMC) and bone marrow
      cells (BMC ). Additional evidence has indicated that TTV is also present in the
      serum of people with hematopoietic malignancies. A significant increase in the
      incidence of lymphoma has recently been observed worldwide. We have investigated
      the presence of TTV DNA in lymph node biopsies of Italian patients affected with
      the most common lymphoma types in Western Countries: follicular lymphoma (FL),
      diffuse large B-cell lymphoma (DLBCL) and nodular sclerosis Hodgkin's disease (NS
      HD). The possible role of a co-infection with Epstein-Barr virus (EBV) has also
      been investigated. DNA was extracted from 73 paraffin-embedded and 38 snap-frozen
      tissue specimens. From these, only 67 samples (29 paraffin-embedded and 38 snap
      frozen tissues) from a total of 56 patients, were suitable for PCR analysis. TTV
      and EBV were detected by PCR using primers from two different conserved region in
      TTV and EBV genomes respectively. TTV DNA was detected in 30.0-50.0% of FL, 30.8%
      of DLBCL and 30.0-50.0% of NS-HD cases, depending on the primers used. All cases
      of non-specific reactive lymphoid hyperplasia (RLH), used as a putative control,
      were negative. The two major TTV genotypes circulating in Italy (G1 and G2) were
      detected in the analysed lymphoid neoplasms. EBV DNA was detected in 40.0% of FL,
      in 72.7%of DLBCL, in 80.0% of SN-HD and in 40.0% of RLH cases. EBV co-infection
      was found in 90% of TTV positive cases. The in situ hybridization assay was
      performed in TTV positive frozen samples. The significant prevalence of TTV DNA
      in lymphocytes circulating in the lymph nodes of both B-cell lymphomas and HD
      reported herewith suggests an implication of TTV infection in the development of
      these lymphoproliferative disorders.

PMID- 12797902
TI  - Heterogeneity of virulence-related properties in Listeria monocytogenes strains
      isolated from patients with haematological malignancies.
AB  - Listeria monocytogenes is an intracellular foodborne pathogen of humans and
      animals for which there are indications of virulence differences among strains.
      Various virulence properties related to different phases of infection process
      were investigated in L. monocytogenes strains isolated from patients affected by
      haematological malignancies. In these isolates, besides to the clinical history,
      we analysed the haemolysin production, the survival to acidic pH, the ability to
      enter and proliferate in human intestinal-like and human macrophagic-like cells,
      as well as the allelic polymorphism of the actA gene involved intracellular
      movement. A general heterogeneity in the virulence properties was detected which
      did not appear correlated with the clinical outcome of listeriosis but more
      probably was influenced by the status of the immune defence of the host.

PMID- 12797903
TI  - No specific reactivity to E. coli glutamic acid decarboxylase from sera of newly
      diagnosed insulin dependent diabetic patients.
AB  - The 65 kD isoform of Glutamic Acid Decarboxylase (GAD), is one of the major
      autoantigens in human type 1 diabetes mellitus. This enzyme shares amino acid
      identity, in select regions already determined as antigenic with its counterpart
      from E. coli. We tested the reactivity of diabetic and normal sera and an E. coli
      GAD-specific monoclonal antibody (2D9) to E. coli GAD by solid phase and
      competition ELISA, as well as immunoblotting to check for cross-reactivity of
      autoantibodies to the two antigens. Specific antibodies for E. coli GAD are
      present in diabetics and normal subjects without any differences in frequency and
      titer. The reactivity of such antibodies in ELISA could be blocked in a dose
      dependent manner by the addition of excess antigen in the liquid phase.
      Furthermore, the monoclonal antibody against E. coli GAD does not recognise human
      recombinant GAD65 in an ELISA. We conclude that there is no basis for cross
      reactivity between the two antigens, and antibody reactivity to GAD65 in man
      cannot arise from cross-reactivity to the E. coli enzyme.

PMID- 12797904
TI  - Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum
      electrolytic workers.
AB  - The purpose of our study is to determine the alteration of neurobehavioral
      parameters, autonomic nervous function and lymphocyte subsets in aluminum
      electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/-
      2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/-
      6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was
      measured by means of graphite furnace atomic absorption spectrophotometer. Normal
      reference group were selected from a flour plant. Neurobehavioral core test
      battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test
      battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to
      measure the lymphocyte subsets of peripheral blood. The mean air aluminum level
      in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum
      of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously
      higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral
      results showed that the scores of DSY, PAC and PA in Al electrolytic workers were
      significantly lower than those of control group, The score of POMSC, POMSF and
      SRT among Al exposed workers were significantly augmented in relation to those of
      control group. Autonomic nervous function test results showed that R-R interval
      variability of maximum ratio of immediately standing up in Al electrolytic
      workers were decreased compare with the control group, while the BP-IS, HR-V, HR
      DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test
      showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This
      study suggests that Al exposure exerts adverse effects on neurobehavioral
      performance, especially movement coordination and negative mood, and
      parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte
      subsets.

PMID- 12797905
TI  - Polyaromatic hydrocarbons administered in humans by dermal route increase total
      IgE.
AB  - Inhalation of polyaromatic hydrocarbons (PAHs) extracted from diesel exhaust
      particles (DEP) enhances local (nasal) production of IgE in humans. The aim of
      the present research is to investigate whether in humans dermal exposure to PAHs
      which are not extracted from DEPs increases serum IgE, and whether host factors
      modify the immunologic effect. In thirty-two patients with acute psoriatic
      lesions, a cream containing 3% of coal tar (which holds a variety of PAHs) was
      applied to the skin for 24 hours. Serum IgE were measured before (IgE0) and four
      (IgE4) and eight (IgE8) days after application. Replicated means were compared by
      analysis of variance for repeated measures and by the Newman-Keuls' test. IgE0,
      IgE4 and IgE8 were 151.19, 159.69 (a 6% excess) and 170.90 kU/L (a 13% excess)
      respectively; pairwise comparison showed IgE8 was significantly higher than IgE0
      (p<0.05). At multiple linear regression analysis, the percentage increase in
      serum IgE across observation days was the dependent variable against age, sex,
      cigarettes/day, urinary 1-pyrenol, atopy, skin area treated, and grams of cream.
      Of the independent variables, only age had a significant (p<0.028) influence: the
      younger the age, the higher the IgE response to PAHs. We conclude that whatever
      the source and the route of entry (skin or respiratory tract), PAHs increase
      total serum IgE, mainly in younger age groups.

PMID- 12797906
TI  - Compartmentalisation between gut and lung mucosae in a model of secondary
      immunodeficiency: effect of thymomodulin.
AB  - Compartmentalisation of mucosal immune response seems to be the result mainly of
      the preferential migration of activated cells back to their inductive sites. The
      aim of this report was to demonstrate, in a model of secondary immunodeficiency
      in Wistar rats (severely protein deprived at weaning and refed with casein 20%;
      group R21), that the oral administration of Thymomodulin (group:R21TmB) has
      different effects on gut and BALT (Bronchus-associated lymphoid tissue). Tissue
      sections (5 mu) were studied by immunohistochemistry 1). The oral administration
      of Thymomodulin restores only in gut Lamina propria (LP) the IgA B and CD4 T cell
      populations to control levels. The CD8a and CD25 subpopulations do not vary in
      gut as they return to control levels when refed with 20% casein diet. All the
      populations mentioned above remained decreased even after receiving Thymomodulin
      by the oral route. However, the same behaviour was observed for the TCR delta T
      cells that were decreased and return to normal levels in both mucosae by the
      effect of the immunomodulator; 2) when studying the iIEL (intestinal
      intraepithelial lymphocytes) CD8 alpha, CD25 and TCR gamma delta T cells, that
      were increased in R21, return to control levels in R21TmB. In BALT
      intraepithelium CD8 alpha and CD25 T cells remained decreased, while only TCR
      gamma delta T cells (increased in R21) return to control values. CONCLUSIONS: 1)
      there exists a compartmentalisation between both mucosae, as T CD4+ and IgA B+
      cells are restored by TmB only in gut; 2) only those iIEL involved in
      inflammation (CD8 alpha+/CD25+ and TCR gamma delta+/CD25+) are normalised by
      means of the Thymomodulin 3) however, in BALT,only TCR gamma delta+ T cells are
      restored 4) the oral administration of the present immunomodulator may be useful
      as a therapeutic agent, although the preferential survival in the tissue of
      initial stimulation is the major factor in the preferential distribution of
      activated cells.

PMID- 12797907
TI  - Interleukin-4 and interferon-gamma production during HIV-1 infection and changes
      induced by antiretroviral therapy.
AB  - Several lines of evidence indicate that a switch of the cytokine pattern from a
      predominant type 1 (antiviral and cell mediated response) to type 2 (polyclonal
      humoral immune response) occurs during the course of Human Immunodeficiency Virus
      1 (HIV-1) infection, and represents a key event in the progression of
      immunodeficiency and dysregulated immune activation. We proposed to further
      investigate this immunological aspect of HIV-1 disease, in naive and in patients
      treated with Highly Active Antiretroviral Therapy (HAART). The prototypic
      cytokines chosen were Interleukin (IL)-4 and Interferon-gamma (IFN-gamma), whose
      in vitro production was determined in mononuclear cell cultures stimulated with
      different T lymphocyte mitogenic agents (anti-CD3, Phytohaemoagglutin-P -PHA-, E.
      coli B04/035 Lipopolysaccharide -LPS-). We classified all the patients on the
      basis of the number of CD4+ lymphocytes and we found a progressive, even if not
      significant decrease in the baseline production of IFN-gamma with the progression
      of the immunodeficiency. The mean value of baseline IFN-gamma in the group of
      patients with CD4+>500 cells/microL was 7.79 +/- 3.1 pg/mL while in the group
      with CD4+<200 cells/microL it was 4.66 +/- 2.22. We didn't find significant
      differences in the baseline production of IL-4 in these groups and in IFN-gamma
      and IL-4 production in LPS-stimulated cultures. We also re-assessed 12 patients
      after one year's follow-up. They presented a significant increase in IFN-gamma
      production compared to the first assessment in the LPS-stimulated cultures
      (baseline IFN-gamma 2.87 +/- 1.17 pg/mL, after 12 months 19.15 +/- 5.19 pg/mL; p=
      0.03). In the 12 patients in follow-up IL-4 production showed a decreased in PHA
      stimulated cultures with mean values of 16.65 +/- 14.32 pg/mL at baseline and
      6.54 +/- 6.54 pg/mL after follow-up. These results highlight the immunorestoring
      effects of HAART. IL-4 production was lower in the treated subjects compared to
      the naive ones in PHA-stimulated cultures (mean values: IL-4=13.42 +/- 11.08
      pg/mL in the naive patients and 9.75 +/- 65 pg/mL in the treated patients). The
      IFN-gamma values in anti-CD3 stimulated cultures were also higher in the treated
      patients, but this increase was not significant.

PMID- 12797908
TI  - Immune system alterations in lung cancer patients.
AB  - The immune system plays an important role in the defense against neoplastic
      disease and immune responses show temporal changes related to circadian
      variations of antibodies, total lymphocytes in the peripheral blood and cell
      mediated immune responses. In this study we evaluate. lymphocyte subpopulations
      and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at
      four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects
      aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects
      suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/
      s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00
      10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were
      calculated, and the presence of circadian rhythmicity was evaluate. When we
      compared AUC values there was a decrease in CD8bright (T suppressor subset) and
      an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer
      patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic
      subset) and CD8bright levels were lower, and CD16 levels were higher in cancer
      patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B
      activated lymphocytes with expression of the a chain of IL-2 receptor) levels
      were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the
      constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the
      variable domain of d chain of T-cell receptor1) levels were lower in cancer
      patients. A clear circadian rhythm was validated for the time-qualified changes
      in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16,
      TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear
      circadian rhythm was validated for the time-qualified changes in CD4 with
      acrophase at night, in the group of cancer patients. Results obtained in our
      study show that lung cancer is associated with anomalies of proportion and
      circadian variations of lymphocyte subsets that must be considered when adoptive
      immunotherapy has to be planned.

PMID- 12797909
TI  - Simple renal cysts in hypertensive patients: relation between cyst growing and
      anti-hypertensive therapy.
AB  - The study investigates relationship between simple renal cyst enlargement studied
      by ultrasonography and anti-hypertensive treatment. To this purpose we enrolled
      42 patients with newly diagnosed hypertension affected by simple renal cysts.
      Fourteen were randomly assigned to treatment with ACE-Inhibitors (group 1),
      twelve to diuretics (group 2) and sixteen to Ca-Antagonists (group 3). Patient
      performed a basal ultrasonography to evaluate basal cyst dimension before
      starting anti-hypertensive treatment. Following 12 months of the anti
      hypertensive regimen, a new echograph was performed to evaluate changes in cyst
      size. A control group consisting of 15 patients with normal blood pressure and
      simple renal cysts was enrolled (group 0). An enlargement of cysts was detected
      in all patients. However, the enlargement observed in patients treated by Ca
      Antagonists was significantly greater than that observed in the other groups
      (p<0.05). Our study supports the hypothesis that Ca-Antagonists may favor cyst
      enlargement by enhancing cyclic AMP production. In fact, cAMP and cAMP agonists
      stimulate fluid secretion by lining cells of the cyst wall, inducing cyst
      enlargement.

PMID- 12797910
TI  - Antiepileptic drugs lower contraceptive sex hormone and increase the risk of
      unplanned pregnancies in women with epilepsy: revisited study.

PMID- 12797911
TI  - [Tuberculous infection in adults].

PMID- 12797912
TI  - [Home enteral nutrition: analysis of efficiency in a Health District].
AB  - INTRODUCTION: Studies on the analysis of direct costs generated by household
      enteral nutrition (HEN) have been scant. The objective of our study was to carry
      out a direct costs analysis of household enteral nutrition using both the
      biochemical and nutritional monitoring values of the nutritional state as a point
      of reference. MATERIAL AND METHODS: Since January 1999 until December 2001, we
      studied a total sample of 102 consecutive patients with indication of household
      nutritional support. The following epidemiological data were obtained in all
      patients: age, sex, and primary condition for which enteral nutrition was
      prescribed; we carried out an anthropometric assessment and a biochemical
      nutritional assessment quarterly. We recorded also the number of episodes of
      diarrhea, vomiting, aspiration pneumonia, and death during the treatment.
      RESULTS: Average age of the patients was 58.7 13.3 years. The number and
      proportion of patients according to primary conditions were the following: 71
      (69.3%) with head and neck cancer, 14 (13.9%) with a neurological condition with
      swallowing disturbance (stroke and/or dementia), 6 (5.9%) with tumors in other
      locations, and 11 (10.9%) with a group of diseases associated with dysphagia or
      anorexia. HEN was administered by oral route in 81 patients (79.4%), by
      nasogastric tube (NGT) in 15 patients (14.7%), by PEG in 5 patients (4.9%) and by
      yeyunostomy in 1 patient (1%). Average duration of HEN was 101 46.9 days. We
      showed a significant improvement of biochemical and anthropometric parameters in
      patients with HEN. The economic analysis of direct costs generated by enteral
      nutrition showed that the total average cost of nutritional formulas and
      expendable equipment utilized (holders, probes and nutritional tubes) was 300,033
      599,203 pesetas/full treatment/patient (1,803 3,601 euros), or a daily average
      cost of 2,970 5,932 pesetas/day/patient (17.8 35.6 euros). In the analysis of
      costs acording to different items, the expendable equipment (nutritional tubes,
      nasogastric tubes and nutritional formula holders) were an average of 1,284 4,571
      pesetas/full treatment/patient (7.7 27.4 euros) (5% in total), and the
      nutritional preparations were an average of 231,313 399,756 pesetas/full
      treatment/patient (1,390.2 2,402 euros) (95%). The patients with greater
      resources expenditure were those with tumors of head and neck. In order to
      analyze the efficiency of this treatment an analysis of costs was carried out for
      each objective parameter indicating nutritional status improvement; that way, the
      increase of 1 g/dl of albumin was an average cost of 103,817 2,897 pesetas (623.9
      17.4 euros), while the increase of 1 kg of weight was an average cost of 857,237
      25,097 pesetas (5,152.1 150.8 euros). CONCLUSIONS. In summary, nutrition enteral
      household was an effective therapy for nutritional status improvement in
      different groups of ambulatory patients. The cost of the nutritional support was
      superior in the group of patients with tumors of the upper aereodigestive system
      because of the greater duration of the treatment and the complex access route.

PMID- 12797913
TI  - [A study of the tuberculous infection in adults].
AB  - Tuberculous infection in adults is not a well known entity in our country,
      despite its epidemiological importance. We have designed an observational study
      in a homogeneous group of adult civil servants of Catalonia (n = 8,202) from 20
      to 54 years old that were submitted to a health examination which included a
      tuberculin test, in order to study the tuberculous infection in these people and
      to evaluate the factors associated with this infection. RESULTS: The global
      prevalence of reactivity in tuberculin test was 22.36% and the prevalence of the
      tuberculous infection was 14.76%. The factors related to the tuberculous
      infection were the following: age, male sex, background of exposure to sources of
      contagion, and previous BCG vaccination. CONCLUSIONS: The prevalence of
      tuberculous infection in adults has declined, and is currently greater in men
      than women, among patients who recognize previous contact with a tuberculous
      patient, and among patients with previous BCG vaccination.

PMID- 12797914
TI  - [Calcaneous ultrasonography as measurement of osteoporosis prevalence in the
      general population in relation to the diagnostic criterion utilized. Data of the
      study GIUMO].
AB  - CONTEXT: In recent years, a large number of techniques have been developed to
      estimate the bone mineral density for the diagnosis of osteoporosis. However,
      diagnostic criteria established by WHO are invariably applied for the
      interpretation of dual radiological densitometry (DEXA), which could not be
      correct in the case of the interpretation of ultrasound. METHOD: We studied 2,589
      randomly chosen people of both sexes, 1,138 males and 1,451 women from 10 to 99
      years, in 11 spanish provinces. We carried out a measurement of the following
      calcaneous ultrasound parameters with the Sahara and Hologic devices: speed of
      the sound (SOS), coefficient of attenuation of wide band (BUA), index of
      consistency (QUI) and estimated bone mineral density (est. BMD). The prevalence
      of osteopenia and osteoporosis was calculated by applying the WHO criteria
      (osteopenia Tscore < or = 1 and osteoporosis Tscore < or = 2.5) and the
      prevalence of osteoporosis by applying a Tscore 1.8 as threshold. RESULTS:
      According to the WHO criteria, osteoporosis (Tscore < or = 2.5) is seen in 1.5 %
      males and 5.9 % females from 51 to 70 years, and in 2.6% males and 22.1% females
      over 70 years. Using a Tscore 1.8 as threshold, osteoporosis prevalence increases
      to 8.2% males and 21.9% females from 51 to 70 years, and to 8.4% males and 40.9%
      females over 70 years. CONCLUSION: Osteoporosis prevalence in spanish people of
      both sexes differs notably when applying the cut off point in a Tscore of 2.5, as
      WHO recommends, or in a Tscore of 1.8 as is suggested by other authors. Consensus
      is necessary to establish the appropriate cut off point or threshold for the
      diagnosis of osteoporosis with quantitative ultrasonography of calcaneum.

PMID- 12797915
TI  - [Hypertension and heart failure in Primary Care and Cardiology consultations of
      in Spain].
AB  - OBJECTIVE: Analyze the results concerning the heart failure population of
      CARDIOTENS 99, a cross-sectional study of hypertension associated with
      cardiovascular disease carried out on 32,051 patients seen in Cardiology and
      Primary Care consultations. METHODS: In the analysis we included prospectively
      demographic, clinical, blood pressure, and therapeutic data of all patients seen
      on a single day by 1,159 physicians (21% cardiologists; 79% Primary Care
      physicians). RESULTS: 4% of the total sample of 32,051 patient had heart failure,
      representing 23% of the patients with heart disease. Median age was 70,8 6,7
      years; 53% were women. Hypertension was the most frequent risk factor, appearing
      in 71% of the patients with heart failure. Hypertension was most frequent in
      Primary Care patients (76% versus 63%; p < 0,01), while ischemic heart disease
      was most frequent in cardiology patients (38% versus 27%; p < 0,01). Cardiology
      patients showed a trend for greater use of drugs in comparison with patients seen
      in primary care consultations but without significant differences (3,39 versus
      3,35; p > 0,05). Diuretics were the drugs with greater prescription (63%). 44%
      patients with heart failure were on an angiotensin-conversing enzyme inhibitor
      and 14% on beta-adrenergic blockers. Systolic blood pressure was well controlled
      in only 19% of hypertensive patients with heart failure, according to the
      international recommendations (< 130 mmHg). The proportion of patients with blood
      pressure higher than 140 mmHg was superior among the patients seen by
      cardiologists than between those seen by Primary Care physicians (57% versus 47%;
      p < 0.01). CONCLUSIONS: Heart failure is often associated with hypertension.
      Control of blood pressure is inadequate in the majority of patients with heart
      failure. Ischemic heart disease is a more frequent cause of in the patients seen
      by cardiologists than in those seen by Primary Care physicians, and hypertension
      is the leading cause of heart failure in these patients. Prescription of drugs
      recommended for the treatment of heart failure it is generally very scant.

PMID- 12797916
TI  - [Kikuchi's histiocytic necrotizing lymphadenitis].
AB  - Necrotizing histiocytic lymphadenitis (NHL) or Kikuchi-Fujimoto disease is an
      infrequent seen clinicopathologic entity that affects most frequently young women
      and individuals of eastern races, and that is characterized by fever and
      adenopathies (basically cervical) and systemic disease even though occasional
      patients present extranodal disease. We present two young women with NHL and
      cutaneous affectation, and with lymphocytic meningitis in one of the patients. We
      discuss the etiology of NHL, the relation of NHL with collagen-vascular diseases
      (basically systemic erythematous lupus) the problem of the pathologic diagnosis,
      and the therapeutic possibilities in these patients.

PMID- 12797917
TI  - [Older patient agitation treatment].

PMID- 12797918
TI  - [Stratification and therapeutic objectives of the cardiovascular risk].

PMID- 12797919
TI  - [Cutaneous lesions and confusional syndrome].

PMID- 12797920
TI  - [Left auricular mass].

PMID- 12797921
TI  - [45-year-old male with bilateral lung infiltrates].

PMID- 12797922
TI  - [Unusual presentation of an abscess by Staphyloccoccus aureus].

PMID- 12797924
TI  - [Patients with multiple hospitalizations: a problem or a stigma?].

PMID- 12797923
TI  - [Seizures and upper digestive hemorrhage associated with antidiarrheal treatment
      with activated coal].

PMID- 12797925
TI  - [Lung emphysema as a rare complication of inhaled cocaine addiction].

PMID- 12797926
TI  - [Use and validity of the 14-3-3 protein test in the diagnosis of prion diseases:
      a 4-year prospective study].
AB  - BACKGROUND AND OBJECTIVES: The 14-3-3 test shows a high efficiency for the
      diagnosis of Creutzfeldt-Jakob disease (CJD), as long as an appropriate clinical
      setting exists. We analyze the evolution of the use and the validity of this test
      in Spain. PATIENTS AND METHOD: From January 1997 to June 2001, 1,092 samples were
      tested in our laboratory; 674 samples were selected for the study. Diagnoses were
      obtained by the referring physicians and the national CJD surveillance system
      according to standard criteria (results of the test were not included). RESULTS:
      The number of samples analyzed (% of follow-up) was: 75 (96%) in 1997, 138
      (82.3%) in 1998, 197 (73%) in 1999 and 264 (59%) in 2000. The negative predictive
      value, sensitivity and specificity for a diagnosis of prion disease revealed
      stable values (95, 86 and 86%, respectively). The positive predictive value (PPV)
      decreased from 77% in 1997 to 51% in 2000 because of an increase of false
      positive (FP) results. Up to 25% of FP might have been excluded through
      neuroimaging or CSF characteristics. CONCLUSIONS: The observed increase of the
      demand suggests that the test is used as a screening technique. In this setting,
      the PPV of the test decreases due to an increase of false-positive results.

PMID- 12797927
TI  - [Prevalence of infection by HIV and hepatitis C virus in a cohort of patients on
      methadone treatment].
AB  - BACKGROUND AND OBJECTIVES: Methadone maintenance treatment reduces drug-related
      harm. The aims of the study were: a) to analyze the temporal tendencies of
      prevalence of infection by HIV and hepatitis C virus, and b) to evaluate if the
      adherence to methadone maintenance treatment protects against the infection by
      HIV and hepatitis C virus. PATIENTS AND METHOD: Retrospective longitudinal study
      with All the 1,487 patients receiving treatment in the Province of Alicante
      between June 1990 and December 1997. The prevalence of infection by HIV and
      hepatitis C virus were computed. The variables associated to the infection by HIV
      and hepatitis C virus were recognized though a model of logistic regression.
      RESULTS: The prevalence of infection by HIV decreased, and the prevalence of
      infection by hepatitis C virus increased along the studied period. The
      independent predictors with regard to the infection by HIV were the age of
      beginning in treatment (odds ratio [OR] = 0.95; 95% confident interval [95%CI],
      0.93-0.97; p < 0.001), total time within treatment (OR = 0.99; 95%CI, 0.98-1.0; p
      = 0.01) and non-parenteral route of administration (OR = 0.25; 95%CI, 0.18-0.33;
      p < 0.001). CONCLUSIONS: To be admitted to methadone maintenance treatment for
      the first time after opiate dependence has been developed and to remain in
      treatment for long periods of time, all that decreases the risk of infection by
      HIV.

PMID- 12797928
TI  - [Secondary Preventive Program of atherosclerosis in a university hospital.
      Results and predictors of clinical course].
AB  - BACKGROUND AND OBJECTIVE: Lipid therapeutic goals are not achieved in a high
      percentage of patients with coronary artery disease (CAD). We describe in this
      paper the methodology and results of the Hospital Universitario de Bellvitge
      Atherosclerosis Secondary Preventive Program (PPSHB), which is aimed at
      preventing ischemic recurrences by controlling atherogenic factors. PATIENTS AND
      METHOD: From January 1992 to December 1996, 882 patients with acute CAD entered
      the PPSHB and were seen on at least 2 occasions at the Unidad de Lipidos y
      Arteriosclerosis during a mean period of 10.4 (3.8) months. In 753 patients data
      on clinical follow-up were available. Follow-up data were collected by telephone
      interview and review of medical records. RESULTS: During the follow-up period at
      the Unidad de Lipidos y Arteriosclerosis, 71.9% of patients achieved the
      therapeutic goals or their LDLc improved >= 15%. These results were seen in
      83.6%, 78.7% and 83.6% of patients with regard to HDLc, triglycerides and
      HDLc/LDLc ratio, respectively, while the percentage of patients receiving lipid
      lowering drugs increased from 28% to 69%. During a follow-up of 33.7 (15.9)
      months, death (all causes; mean survival time: 20 [13.4] months) occurred in 41
      patients (5.4%). On the other hand, hospitalization for cardiovascular disease
      was required in 113 patients (15%) during a mean follow-up until the first
      admission of 18.4 (14.2) months. The main independent predictor of unfavourable
      clinical course was not to reach the HDLc/LDLc ratio goal (HDLc/LDLc >= 0.27 or
      an increase >= 15%; OR = 2.1; 95% CI, 1.1-4.03). CONCLUSIONS: A systematic
      secondary preventive strategy may help achieve an adequate control of
      dyslipidemia in most CAD patients. In these patients, achieving the HDLc/LDLc
      therapeutic goal is associated with a less than half risk of hospitalization for
      cardiovascular disease or death from any cause.

PMID- 12797929
TI  - [Relation between clinical presentation and prognosis of patients with papillary
      thyroid microcarcinoma].
AB  - BACKGROUND AND OBJECTIVE: We aimed to analyze patients with papillary thyroid
      microcarcinoma (PTM) in order to establish the prognosis according to the
      differences observed between those diagnosed before surgery and those diagnosed
      postoperatively. PATIENTS AND METHOD: Retrospective study of 83 PTM patients who
      were distributed in 2 groups. Clinical, histological and follow-up data were
      compared. Survival and disease-free interval (DFI) were analyzed in both groups.
      RESULTS: Group A (diagnosed before surgery): 30 patients (36.1%); group B
      (diagnosed postoperatively): 53 patients (63.9%). Five group A patients had a
      relapse. Overall survival was 98.8% and overall DFI was 94% (83.3% in group A and
      100% in group B, p = 0.01). CONCLUSIONS: It is useful to differentiate patients
      with PTM diagnosed before surgery from those whose PTM was diagnosed after since
      their evolution is different.

PMID- 12797930
TI  - [Fondaparinux for thrombosis prevention after orthopaedic surgery: a
      revolution?].

PMID- 12797931
TI  - [Ciguatera poisoning in Spanish travellers].
AB  - BACKGROUND AND OBJECTIVE: Ciguatera poisoning appears after ingestion of
      contaminated fish from tropical coral reefs. Due to the diversity of clinical
      symptoms and the absence of a specific test in humans, the diagnosis is often
      difficult. PATIENTS AND METHOD: A retrospective study of 10 patients consulting
      for a clinical and epidemiological picture compatible with ciguatera poisoning
      after a trip to tropical countries between 1993 and 2000. RESULTS: Most
      infections but one were acquired in the Caribbean area and there were 8 females.
      Clinical manifestations started within the first 24 hours after fish ingestion.
      Chief symptoms were diarrhea and nausea, followed by neurological symptoms,
      mainly limbs paresthesias that persisted for several weeks. CONCLUSIONS: The
      severity of clinical symptoms was variable and not related to age or initial
      symptoms. Ciguatera poisoning has to be considered in the diagnosis of acute
      gastroenteritis affecting travellers to tropical areas.

PMID- 12797932
TI  - [Management of lymphoproliferative disorders associated to organ
      transplantation].

PMID- 12797933
TI  - [Genetics and Alzheimer disease].

PMID- 12797934
TI  - [Availability of drugs in the European Union. The case of antiplatelet agents].

PMID- 12797935
TI  - [Remission of longlasting autoimmune thrombocytopenic purpura after allogeneic
      hematopoietic stem cell transplantation for chronic myeloid leukemia].

PMID- 12797936
TI  - [Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase
      deficiency].

PMID- 12797937
TI  - [On severe acute respiratory syndrome (SARS): epidemics in the context of
      globalization].

PMID- 12797938
TI  - [Solitary pulmonary nodule: how has diagnostic assessment changed?].

PMID- 12797939
TI  - [A model to predict death after lung cancer resection: applicability to
      individual cases].
AB  - OBJECTIVE: To evaluate the reliability of a logistic regression model to predict
      individual risk of death related to lung cancer resection. METHOD: A study of 515
      consecutive patients undergoing anatomical pulmonary resection (lobectomy or
      pulmonectomy) for lung cancer between January 1994 and December 2001. Dependent
      variable: death in or out of hospital within 30 days of surgery. Continuous
      independent variables: age, body mass index, and percent of predicted
      postoperative FEV1. Binary independent variables: ischemic heart disease,
      diabetes mellitus, preoperative arrhythmia, induction chemotherapy, type of
      resection (lobectomy or pneumonectomy), chest wall resection, tumor extension
      (localized or extended tumor) and perioperative blood transfusion. All data were
      gathered prospectively. A univariate analysis was performed using contingency
      tables for binary variables and analysis of variance for continuous ones;
      stepwise logistic regression analysis was then performed and the likelihood of
      death for each individual was calculated. A receiver operating characteristic
      (ROC) curve was constructed with the data, using surgical death as the state
      variable. RESULTS: The following variables were found to be independently related
      to death in the univariate analysis: age (p < 0.001, odds ratio 1.11); tumor
      extension (p = 0.002; OR 3.47) and perioperative transfusion (p = 0.004; OR
      3.87). The area under the ROC curve was 0.77, attributable to high specificity
      given that none of the complications could have been predicted. CONCLUSION:
      Although some variables are related to surgical death, the described model is not
      able to give a prediction. Therefore, the model is of little use for application
      in making decisions about individual cases.

PMID- 12797940
TI  - [Usefulness of chest sonography in a respiratory medicine unit].
AB  - Chest ultrasound, a diagnostic technique used mainly by radiologists, is useful
      for managing pleural effusion. Sonography and computed tomography (CT) are
      complementary, although the former is more accessible to clinicians because it is
      safe and easy to use and because results are available quickly. We evaluated the
      utility of chest sonograms in a respiratory medicine unit managed by
      pneumologists. During the period under study, requests for CT scans to manage
      complicated pleural effusions decreased as the use of sonograms increased. We
      conclude that ultrasound imaging is useful in the hands of pneumologists who use
      the technique to diagnose pleural effusions.

PMID- 12797941
TI  - [Reliability of Venturi oxygen therapy systems].
AB  - Venturi systems are among the most widely used devices for delivering oxygen
      therapy. Nevertheless, rigorous quality control of their reliability is lacking.
      In this study we used mass spectrometry to evaluate Venturi systems sold by
      various companies in Spain. We also studied tolerance under various conditions
      (changes in oxygen flow and with increased system resistance). Fixed systems were
      found to comply well with recommendations, whereas none of the variable systems
      complied. One system (Oxigem Variable) was unable to provide an oxygen
      concentration below 31% when set to deliver at 24% to 28%. We conclude that the
      variable masks available in Spain do not comply with European Union
      recommendations and the range of error of one of them (Oxigem Variable) means it
      is not clinically useful. Fixed systems were the most reliable ones in our
      market, and airlife and intersurgical devices were the variable systems that best
      approximated the reliability of fixed systems.

PMID- 12797942
TI  - [Efficacy of an antibacterial filter for preventing contamination of respiratory
      function diagnostic equipment].
AB  - OBJECTIVES: Devices to assess lung function are a potential source of nosocomial
      infection. Our aims in this study were: 1) to determine the efficacy of an
      antimicrobial filter to prevent contamination of a multifunctional device; 2) to
      assess the ability of the filter to prevent cross contamination of individuals
      being tested; and 3) to evaluate the efficacy of the recommendations of the
      Spanish Society of Respiratory Diseases and Thoracic Surgery for disinfecting
      lung function equipment. DESIGN: In this prospective, randomized study in two
      phases we used filters in phase 1 but not in phase 2. A pharyngeal swab culture
      was started within 7 days of a patient's lung function test. Swab samples for
      culturing were taken from three different places in the equipment at the
      beginning and end of each working day. PATIENTS: Sixty-five patients (31 in phase
      1 and 34 in phase 2) were studied. Thirty-two (49.2%) were men and the mean age
      was 49.4 15.7 years. RESULTS: Significantly less equipment contamination was
      found in phase 1 (4.2%) than in phase 2 (21%). We detected no cases of cross
      contamination using the criteria in this study. No cultures from any of the
      samples taken before exploration were positive. CONCLUSIONS: a) The antimicrobial
      filter used is effective for preventing the contamination of lung function
      testing equipment, b) throughout both phases of the study, we observed no cross
      contamination of patients tested, such that we cannot conclude that the
      antimicrobial filter is effective for preventing possible nosocomial infections,
      c) the recommendations of SEPAR for disinfecting lung function equipment are
      effective.

PMID- 12797943
TI  - [Analysis of logistical and organizational aspects of a cruise for patients with
      chronic respiratory insufficiency. The RESpIRA Expedition and the COPD Cruise].
AB  - Patients with chronic respiratory insufficiency who are receiving domiciliary
      oxygen therapy and mechanical ventilation report great difficulty in taking
      complex trips involving several destinations and prolonged stays away from home.
      Such patients share a common need for home equipment whose technology is
      relatively sophisticated, a condition that limits their freedom of movement. We
      are referring to systems for delivering oxygen therapy and mechanical
      respirators. Given that such patients have problems traveling by air, we
      hypothesized that a cruise would be an ideal alternative, given that travel would
      take place in the hotel itself. A cruise would facilitate the logistics of the
      journey, given that the equipment would have to be set up at only one setting.
      Working with these assumptions, we have thus far organized two cruises for
      chronic respiratory insufficiency patients: the "RESpIRA Expedition" and the
      "COPD Cruise". Our experience shows that the organizational problems to be coped
      with are patient recruitment, financing and choice of itinerary. With those
      aspects clear, organizers must then obtain the authorization of the cruise
      operator, including the approval of the medical and safety personnel on board.
      After obtaining permission for the cruise and as soon as the organizers know how
      many patients will travel, a list of oxygen therapy equipment (respirators and
      disposable supplies) must be compiled. Finally, equipment suppliers must be
      found. Afterwards, all that remains is to enjoy the trip. The participation of
      physicians responsible for domiciliary oxygen therapy and mechanical ventilation
      programs is essential for making patients feel safe and for assuring solutions
      for technical and medical problems that might arise.

PMID- 12797945
TI  - [Alveolar hemorrhage associated with intestinal inflammatory disease and
      Hashimoto thyroiditis].
AB  - Diffuse alveolar hemorrhage (DAH) is characterized by diffuse bleeding into
      alveolar spaces. Three histopathological patterns may be seen: 1) pulmonary
      capillaritis due to immunological aggression to the membrane, 2) diffuse alveolar
      damage within the context of acute respiratory distress syndrome, and 3) and
      "bland" DAH without alveolar or capillary damage. In the first two groups,
      pulmonary damage usually occurs within the context of a systemic disease. In the
      last, injury is usually found only in the lung, an entity called pulmonary
      hemosiderosis. We present a case of DAH with neither capillaritis nor diffuse
      alveolar damage in association with inflammatory bowel disease and Hashimoto
      thyroiditis. The case is interesting both because the association has not yet
      been described in the literature and because the presence of alveolar bleeding
      without evident tissue damage within the context of known autoimmune diseases may
      extend the field to include a new pathophysiological mechanism of pulmonary
      hemorrhage.

PMID- 12797944
TI  - [Second consensus report on the use of antimicrobial agents in exacerbations of
      chronic obstructive pulmonary disease].
AB  - Aware of the importance of chronic obstructive pulmonary disease (COPD), a panel
      of experts belonging to the Spanish Society of Respiratory Medicine and Thoracic
      Surgery (SEPAR), the Spanish Society of Chemotherapy (SEQ) and the Spanish
      Society of Family and Community Medicine (SEMFyC) issued a statement of consensus
      in 2000 to serve as the basis for adequate antibiotic control of the disease.
      Three years later, in accordance with significant scientific progress made in
      this area, the statement has been thoroughly revised. The new paper in fact
      constitutes a second consensus statement on the use of antibiotics in COPD
      exacerbations. When several scientific associations expressed interest in joining
      the project and contributing to it the Spanish Society of Emergency Medicine
      (SEMES), the Spanish Society of General Medicine (SEMG) and the Spanish Society
      of Rural and General Medicine (SEMERGEN) their incorporation led SEPAR and SEMFyC
      to change the structure of the statement and certain aspects of its content.
      Additionally, a new group of antibiotics, the ketolides, has joined the
      therapeutic arsenal. Telithromycin, the single representative of the group for
      the moment, can be considered not only an alternative treatment but even the drug
      of choice in certain clinical settings that are analyzed in the new statement.
      Those developments, along with others, such as the increasingly recognized action
      of levofloxacin against Pseudomonas aeruginosa and the steady action of
      amoxicillin with clavulanic acid when administered at recommended doses every 8
      hours, provide new antimicrobial therapeutic protocols for COPD. Finally, the
      statement includes a scientific analysis of other groups of antimicrobial agents
      (macrolides, oral cephalosporins, etc.) and guidelines for both primary care
      physicians and specialists to follow when prescribing them.

PMID- 12797946
TI  - [Lung toxicity due to thalidomide].

PMID- 12797948
TI  - [Abbreviations: Must we accept them?].

PMID- 12797947
TI  - [Carcinosarcoma of the lung].

PMID- 12797949
TI  - [On Quality of clinical trials published in Spain on asthma in comparison to
      trials in English language journals].

PMID- 12797950
TI  - Together at last: bHLH and LIM-HD regulators cooperate to specify motor neurons.
AB  - bHLH and LIM-HD transcription factors were originally thought to act at different
      stages of neurogenesis: bHLHs as neuronal "inducers" and LIM-HDs as postmitotic
      subtype determinants. These distinctions are becoming blurred, and a current
      study by Lee and Pfaff in this issue of Neuron shows that interaction between
      these factors functions to synchronize neurogenesis with neuronal cell type
      specification.

PMID- 12797951
TI  - Glutamate-dependent stabilization of presynaptic terminals.
AB  - Dissecting the mechanisms underlying synapse formation and elimination is
      fundamental to understand how the nervous system is constructed and subsequently
      modified. Two studies by Tashiro et al. and by Hashimoto and Kano in this issue
      of Neuron provide new insights into the roles of neurotransmitter glutamate
      release in regulating the motility of hippocampal mossy fiber filopodia and
      synaptic competition among climbing fibers.

PMID- 12797952
TI  - Cholinergic modulation of skill learning and plasticity.
AB  - The basal forebrain cholinergic system strongly influences both cortical
      plasticity and learning. Directly relating these two roles has proven difficult.
      New results indicate that nucleus basalis lesions prevent motor cortex map
      plasticity and impair skill learning. These results strengthen the hypothesis
      that nucleus basalis gates neural plasticity necessary for instrumental learning.

PMID- 12797953
TI  - Polyglutamines placed into context.
AB  - Nine inherited neurodegenerative disorders result from polyglutamine expansions.
      Two recently published papers on spinocerebellar ataxia type 1, together with
      studies on spinobulbar muscular atrophy last year, indicate that host protein
      context is the key arbiter of polyglutamine disease protein toxicity. This
      insight may represent the most important development in the field since the
      recognition of nuclear inclusions or the propensity of polyglutamine to
      aggregate. Indeed, an intimate and inextricable relationship may exist between
      polyglutamine neurotoxicity and the normal interactions, domains, modifications,
      and functions of the respective disease proteins.

PMID- 12797954
TI  - Diverse targets for intervention during inflammatory and neurodegenerative phases
      of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune central nervous system (CNS)
      demyelinating disease that causes relapsing and chronic neurologic impairment.
      Recent observations have altered certain traditional concepts regarding MS
      pathogenesis. A greater diversity of cell types and molecules involved in MS is
      now evident. While remyelination can occur during the early inflammatory phase
      when damage may be reversible, it is impaired in the later stages, which involve
      axonal death. These observations have important therapeutic implications.

PMID- 12797955
TI  - Dynamics of orientation selectivity in the primary visual cortex and the
      importance of cortical inhibition.
AB  - To test theories of orientation selectivity in primary visual cortex (V1), we
      have done experiments to measure the dynamics of orientation tuning of single
      neurons in the V1 cortex of macaque monkeys. Based on our dynamics results, we
      propose that a V1 cell's orientation selectivity is generated mainly by both
      tuned enhancement and global suppression. Enhancement near the preferred
      orientation is probably caused by feed-forward input from LGN (plus amplification
      by cortical-cortical interaction). Global suppression could be supplied by
      cortical inhibition. Additionally, in about 1/3 of V1 neurons (usually the most
      sharply tuned) there is tuned suppression, centered near the cell's preferred
      orientation but broader than tuned enhancement. These mechanisms also can explain
      important features of steady-state selectivity in the V1 neuron population.
      Furthermore, similar neuronal mechanisms may be used generally throughout the
      cerebral cortex.

PMID- 12797956
TI  - Hypothalamic orexin neurons regulate arousal according to energy balance in mice.
AB  - Mammals respond to reduced food availability by becoming more wakeful and active,
      yet the central pathways regulating arousal and instinctual motor programs (such
      as food seeking) according to homeostatic need are not well understood. We
      demonstrate that hypothalamic orexin neurons monitor indicators of energy balance
      and mediate adaptive augmentation of arousal in response to fasting. Activity of
      isolated orexin neurons is inhibited by glucose and leptin and stimulated by
      ghrelin. Orexin expression of normal and ob/ob mice correlates negatively with
      changes in blood glucose, leptin, and food intake. Transgenic mice, in which
      orexin neurons are ablated, fail to respond to fasting with increased wakefulness
      and activity. These findings indicate that orexin neurons provide a crucial link
      between energy balance and arousal.

PMID- 12797957
TI  - Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice:
      molecular genetic dissection of Non-REM and REM sleep regulatory processes.
AB  - Narcolepsy-cataplexy, a neurological disorder associated with the absence of
      hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying
      problems: inability to maintain wakefulness and intrusion of rapid eye movement
      (REM) sleep into wakefulness. Here we document, using behavioral,
      electrophysiological, and pharmacological criteria, two distinct classes of
      behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both
      OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal
      attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted
      wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy
      like attacks of REM sleep, whereas orexin(-/-) mice are severely affected.
      Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in
      the hypothalamus, which gate non-REM sleep onset. While normal regulation of
      wake/non-REM sleep transitions depends critically upon OX2R activation, the
      profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy
      syndrome emerges from loss of signaling through both OX2R-dependent and OX2R
      independent pathways.

PMID- 12797958
TI  - Synchronization of neurogenesis and motor neuron specification by direct coupling
      of bHLH and homeodomain transcription factors.
AB  - Inductive signaling leads to the coactivation of regulatory pathways for
      specifying general neuronal traits in parallel with instructions for neuronal
      subtype specification. Nevertheless, the mechanisms that ensure that these
      pathways are synchronized have not been defined. To address this, we examined how
      bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with
      LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype
      specification. We found that Ngn2 and NeuroM transcriptionally synergize with
      Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19
      stem cells. The mechanism underlying this cooperativity is based on interactions
      that directly couple the activity of the bHLH and LIM-HD proteins, mediated by
      the adaptor protein NLI. This functional link acts to synchronize neuronal
      subtype specification with neurogenesis.

PMID- 12797959
TI  - Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and
      sodium channel stabilization.
AB  - Dystroglycan is a central component of the dystrophin-glycoprotein complex
      implicated in the pathogenesis of several neuromuscular diseases. Although
      dystroglycan is expressed by Schwann cells, its normal peripheral nerve functions
      are unknown. Here we show that selective deletion of Schwann cell dystroglycan
      results in slowed nerve conduction and nodal changes including reduced sodium
      channel density and disorganized microvilli. Additional features of mutant mice
      include deficits in rotorod performance, aberrant pain responses, and abnormal
      myelin sheath folding. These data indicate that dystroglycan is crucial for both
      myelination and nodal architecture. Dystroglycan may be required for the normal
      maintenance of voltage-gated sodium channels at nodes of Ranvier, possibly by
      mediating trans interactions between Schwann cell microvilli and the nodal
      axolemma.

PMID- 12797960
TI  - PDZ-containing proteins provide a functional postsynaptic scaffold for nicotinic
      receptors in neurons.
AB  - Protein scaffolds are essential for specific and efficient downstream signaling
      at synapses. Though nicotinic receptors are widely expressed in the nervous
      system and influence numerous cellular events due in part to their calcium
      permeability, no scaffolds have yet been identified for the receptors in neurons.
      Here we show that specific members of the PSD-95 family of PDZ-containing
      proteins are associated with specific nicotinic receptor subtypes. At
      postsynaptic sites, the PDZ scaffolds are essential for maturation of functional
      nicotinic synapses on neurons. They also help mediate downstream signaling as
      exemplified by activation of transcription factors. By tethering components to
      postsynaptic nicotinic receptors, PDZ scaffolds can organize synaptic structure
      and determine which calcium-dependent processes will be subject to nicotinic
      modulation.

PMID- 12797961
TI  - Bidirectional regulation of hippocampal mossy fiber filopodial motility by
      kainate receptors: a two-step model of synaptogenesis.
AB  - The rapid motility of axonal filopodia and dendritic spines is prevalent
      throughout the developing CNS, although the function of this motility remains
      controversial. Using two-photon microscopy, we imaged hippocampal mossy fiber
      axons in slice cultures and discovered that filopodial extensions are highly
      motile. Axonal filopodial motility is actin based and is downregulated with
      development, although it remains in mature cultures. This motility is correlated
      with free extracellular space yet is inversely correlated with contact with
      postsynaptic targets, indicating a potential role in synaptogenesis. Filopodial
      motility is differentially regulated by kainate receptors: synaptic stimulation
      of kainate receptors enhances motility in younger slices, but it inhibits it in
      mature slices. We propose that neuronal activity controls filopodial motility in
      a developmentally regulated manner, in order to establish synaptic contacts in a
      two-step process. A two-step model of synaptogenesis can also explain the
      opposite effects of neuronal activity on the motility of dendritic protrusions.

PMID- 12797962
TI  - Functional differentiation of multiple climbing fiber inputs during synapse
      elimination in the developing cerebellum.
AB  - We studied how physiological properties of cerebellar climbing fiber (CF) to
      Purkinje cell (PC) synapses change during developmental transition from multiple
      to mono CF innervation onto each PC. From P3 to P6, differences in the strengths
      of multiple CFs became larger. Around P10, each PC was either monoinnervated by
      one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus
      a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple
      vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but
      less frequently from CF-multi-W and neonatal CFs. We also present evidence
      suggesting that weaker CFs with lower probability of multivesicular release would
      be withdrawn preferentially. The results suggest that differentiation into strong
      and weak CFs with high and low probabilities of multivesicular release precedes
      developmental CF synapse elimination.

PMID- 12797963
TI  - Optical quantal analysis reveals a presynaptic component of LTP at hippocampal
      Schaffer-associational synapses.
AB  - The mechanisms by which long-term potentiation (LTP) is expressed are
      controversial, with evidence for both presynaptic and postsynaptic involvement.
      We have used confocal microscopy and Ca(2+)-sensitive dyes to study LTP at
      individual visualized synapses. Synaptically evoked Ca(2+) transients were imaged
      in distal dendritic spines of pyramidal cells in cultured hippocampal slices,
      before and after the induction of LTP. At most synapses, from as early as 10 min
      to at least 60 min after induction, LTP was associated with an increase in the
      probability of a single stimulus evoking a postsynaptic Ca(2+) response. These
      observations provide compelling evidence of a presynaptic component to the
      expression of early LTP at Schaffer-associational synapses. In most cases, the
      store-dependent evoked Ca(2+) transient in the spine was also increased after
      induction, a novel postsynaptic aspect of LTP.

PMID- 12797964
TI  - A novel network of multipolar bursting interneurons generates theta frequency
      oscillations in neocortex.
AB  - GABAergic interneurons can phase the output of principal cells, giving rise to
      oscillatory activity in different frequency bands. Here we describe a new subtype
      of GABAergic interneuron, the multipolar bursting (MB) cell in the mouse
      neocortex. MB cells are parvalbumin positive but differ from fast-spiking
      multipolar (FS) cells in their morphological, neurochemical, and physiological
      properties. MB cells are reciprocally connected with layer 2/3 pyramidal cells
      and are coupled with each other by chemical and electrical synapses. MB cells
      innervate FS cells but not vice versa. MB to MB cell as well as MB to pyramidal
      cell synapses exhibit paired-pulse facilitation. Carbachol selectively induced
      synchronized theta frequency oscillations in MB cells. Synchrony required both
      gap junction coupling and GABAergic chemical transmission, but not excitatory
      glutamatergic input. Hence, MB cells form a distinct inhibitory network, which
      upon cholinergic drive can generate rhythmic and synchronous theta frequency
      activity, providing temporal coordination of pyramidal cell output.

PMID- 12797965
TI  - Lesions of the Basal forebrain cholinergic system impair task acquisition and
      abolish cortical plasticity associated with motor skill learning.
AB  - The contribution of the basal forebrain cholinergic system in mediating
      plasticity of cortical sensorimotor representations was examined in the context
      of normal learning. The effects of specific basal forebrain cholinergic lesions
      upon cortical reorganization associated with learning a skilled motor task were
      investigated, addressing, for the first time, the functional consequences of
      blocking cortical map plasticity. Results demonstrate that disrupting basal
      forebrain cholinergic function disrupts cortical map reorganization and impairs
      motor learning. Cholinergic lesions do not impair associative fear learning or
      overall sensorimotor function. These results support the hypothesis that the
      basal forebrain cholinergic system may be specifically implicated in forms of
      learning requiring plasticity of cortical representations.

PMID- 12797966
TI  - Dissociating neural mechanisms of temporal sequencing and processing phonemes.
AB  - Using fMRI, we sought to determine whether the posterior, superior portion of
      Broca's area performs operations on phoneme segments specifically or implements
      processes general to sequencing discrete units. Twelve healthy volunteers
      performed two sequence manipulation tasks and one matching task, using strings of
      syllables and hummed notes. The posterior portion of Broca's area responded
      specifically to the sequence manipulation tasks, independent of whether the
      stimuli were composed of phonemes or hummed notes. In contrast, the left
      supramarginal gyrus was somewhat more specific to sequencing phoneme segments.
      These results suggest a functional dissociation of the canonical left hemisphere
      language regions encompassing the "phonological loop," with the left posterior
      inferior frontal gyrus responding not to the sound structure of language but
      rather to sequential operations that may underlie the ability to form words out
      of dissociable elements.

PMID- 12797967
TI  - To the heroes of Columbia, departed for science and discovery. Manned space
      flights do better than robots.

PMID- 12797968
TI  - Genetic variability and reproductive mode of Aspergillus fumigatus.
AB  - Aspergillus fumigatus, an important human pathogen, has been the subject of
      numerous epidemiological studies. This review gives a summary of the techniques
      used for revealing the genetic variability of A. fumigatus, including multilocus
      enzyme electrophoresis and methods based on DNA hybridization and amplification.
      Such studies have provided raw data for examining the structure of A. fumigatus
      populations. Several methods have been described for distinguishing recombination
      from clonality in fungal populations. In our studies, both the index of
      association test and the parsimony tree length permutation test were used for
      examining the reproductive mode of Aspergillus fumigatus populations. The tests
      were performed on isoenzyme and sequence specific DNA primer analysis data
      gathered from the literature. Both tests, together with other observations,
      supported the premise that recombination played an important role in A. fumigatus
      populations. A so-called epidemic population structure was observed in local
      populations isolated from patients. The prevalence of a single or some related
      electrophoretic types in such environments was attributed to some kind of
      selection pressure. Network methods were also used successfully to visualize the
      recombining structures of A. fumigatus populations. The applied techniques did
      not enable us to distinguish between the alternative hypotheses of whether past
      meiotic exchanges, parasexuality or a cryptic sexual stage were responsible for
      the recombining population structure of A. fumigatus.

PMID- 12797969
TI  - The origin, emergence and evolutionary genetics of dengue virus.
AB  - Dengue is one of the most important emerging viruses, posing a threat to one
      third of the global human population. Herein we show how the comparative analysis
      of gene sequence data has shed light on the origin and spread of dengue virus, as
      well as on the evolutionary processes that structure its genetic diversity. This
      reveals that dengue virus has a relatively recent evolutionary history, with the
      four serotypes originating approximately 1000 years ago and only establishing
      endemic transmission in humans in the last few hundred years. However, its place
      of origin remains uncertain as does the extent of genetic and phenotypic
      diversity present in the sylvatic (primate) transmission cycle. Although there is
      some evidence that viral strains differ in key phenotypic features such as
      virulence, and for positive selection at immunologically important sites, it
      seems likely that stochastic processes also play a major role in shaping viral
      genetic diversity, with lineage extinction a common occurrence. A more complete
      understanding of the evolution and epidemiology of dengue virus, particularly
      with respect to the aetiology of severe disease, will require large-scale
      prospective studies and the comparative analysis of complete genome sequences.

PMID- 12797970
TI  - Genetic diversity within the morphological species Giardia intestinalis and its
      relationship to host origin.
AB  - A genetic analysis of Giardia intestinalis, a parasitic protozoan species that is
      ubiquitous in mammals worldwide, was undertaken using organisms derived from a
      variety of mammalian hosts in different geographical locations. The test panel of
      53 Giardia isolates comprised 48 samples of G. intestinalis, including
      representatives of all known genetic subgroups, plus an isolate of G. ardeae and
      four isolates of G. muris. The isolates were compared by allozymic analysis of
      electrophoretic data obtained for 21 cytosolic enzymes, representing 23 gene
      loci. Neighbour Joining analysis of the allelic profiles supported the monophyly
      of G. intestinalis but showed that the species encompasses a rich population
      substructure. Seven major clusters were evident within G. intestinalis,
      corresponding to lineages designated previously as genetic assemblages A-G. Some
      genotypes, e.g. those defining assemblage A, are found in divergent host species
      and may be zoonotic. However other genotypes, e.g. those defining assemblages C
      G, appear to be confined to particular hosts or host groups. The findings
      reinforce other evidence that G. intestinalis, which was defined on the basis of
      morphological criteria only, is a species complex.

PMID- 12797971
TI  - Parity between kinetoplast DNA and mini-exon gene sequences supports either
      clonal evolution or speciation in Trypanosoma rangeli strains isolated from
      Rhodnius colombiensis, R. pallescens and R. prolixus in Colombia.
AB  - Trypanosoma rangeli are kinetoplastid protozoa which have been largely recognized
      and defined in several Latin American countries in relation to T. cruzi, because
      the two trypanosome species are frequently found in mixed infections in
      triatominae vectors, humans and a variety of wild and domestic mammals. We report
      the molecular characterization of 18 T. rangeli strains isolated from the
      salivary glands of naturally infected Rhodnius colombiensis, R. pallescens and R.
      prolixus by using two independent set of molecular markers. kDNA and mini-exon
      amplification indicated dimorphism within both DNA sequences: KP1, KP2 and KP3 or
      KP2 and KP3 products for kDNA mini-circles and 380 or 340bp products for the mini
      exon. One of two associations was observed within individual strains: KP1, KP2
      and KP3 kDNA products with the 340bp mini-exon product and the KP2 and KP3 kDNA
      products with the 380bp mini-exon product. Independent mitochondrial and nuclear
      molecular markers showed a clear division of T. rangeli into two major
      phylogenetic groups associated with specific vectors in Colombia and in other
      Latin America countries. These results support either clonal evolution or
      speciation in T. rangeli populations, probably derived as a secondary adaptation
      to their parasitic condition in triatomine vectors.

PMID- 12797972
TI  - Mycoplasma pneumoniae: a reduced-genome intracellular bacterial pathogen.
AB  - Mycoplasma pneumoniae has classically been considered an extracellular (or
      membrane-associated) organism. Nevertheless, the recently elucidated genomic
      structure of this pathogen strongly suggest that this organism may have been
      subjected to the process of reductive genetic evolution which is characteristic
      of intracellular bacteria. We studied the Mycoplasma pneumoniae RYC15989 strain,
      recovered from a pericardial biopsy sample from a patient with atypical pneumonia
      and acute pericarditis. The interaction of this strain with human hepatocytes Hep
      G2 and mouse neuroblastoma N2-A cell lines was investigated. Confocal laser
      scanning microscopy and electronic microscopy evidence is presented of the
      intracellular location of fluorochrome-labelled Mycoplasma pneumoniae in cell
      lines infected with the organism in vitro. This finding provides preliminary
      evidence of cellular invasive capacity of Mycoplasma pneumoniae and casts some
      new light on the pathogenic potential of Mycoplasma pneumoniae in host infection.

PMID- 12797974
TI  - Phylogenetic analysis of CSP and MSP-9 gene sequences demonstrates the close
      relationship of Plasmodium coatneyi to Plasmodium knowlesi.
AB  - Plasmodium coatneyi is a simian malaria parasite with various biological features
      similar to the human malaria P. falciparum and potential as a model for severe
      cases of malaria. We have characterized two single-copy genes from P. coatneyi,
      the circumsporozoite protein and merozoite surface protein-9 genes, and
      determined its phylogenetic relationship among Plasmodium species. This study
      demonstrates that while it has similarities to P. falciparum, P. coatneyi belongs
      to a distant clade including several simian malaria parasites and the human
      malaria P. vivax. P. coatneyi forms a monophyletic group with P. knowlesi,
      demonstrating their close relationship despite some very distinctive biological
      characteristics.

PMID- 12797976
TI  - MEEGID VI: Sixth International Meeting on Molecular Epidemiology and Evolutionary
      Genetics of Infectious Diseases. Paris, France, 23-27 July 2002. Abstracts.

PMID- 12797977
TI  - Infectious diseases and the Human Genome Diversity Project.

PMID- 12797978
TI  - Karyotypic similarity identifies multiple host-shifts of a pathogenic fungus in
      natural populations.
AB  - The detection of incipient host-shifts is important to the study of emergent
      diseases because it allows the examination of ecological and genetic conditions
      that favor novel inter-species transmission. Mixed populations of Silene
      latifolia and Silene vulgaris were investigated for the putative occurrence of
      host-shifts by the fungal plant pathogen Microbotryum violaceum (the cause of
      anther-smut disease) between S. latifolia (a common host for the pathogen) and S.
      vulgaris (a rare host). Samples of the fungus from mixed and pure host
      populations were studied for variation in their electrophoretic karyotypes. A
      karyotype distance matrix showed that fungal samples clustered by locality, but
      not by host species. Fungal samples from S. vulgaris were indistinguishable from
      sympatric samples from S. latifolia in multiple cases. The results indicated at
      least two independent host-shifts, one in the US and perhaps two in Italy. The
      karyotype and ecological data indicate that the direction of the host-shifts is
      from S. latifolia to S. vulgaris.

PMID- 12797973
TI  - High rates of recombination in otitis media isolates of non-typeable Haemophilus
      influenzae.
AB  - Non-typeable (NT) or capsule-deficient, Haemophilus influenzae (Hi) is a common
      commensal of the upper respiratory tract of humans and can be pathogenic
      resulting in diseases such as otitis media, sinusitis and pneumonia. The
      lipopolysaccharide (LPS) of NTHi is a major virulence factor that displays
      substantial intra-strain and inter-strain variation of its oligosaccharide
      structures. To investigate the genetic basis of LPS variation we sequenced
      internal regions of each of seven genes required for the biosynthesis of either
      the inner or the outer core oligosaccharide structures. These sequences were
      obtained from 25 representative NTHi isolates from episodes of otitis media. We
      found abundant evidence of recombination among LPS genes of NTHi, a finding in
      marked contrast to previous analyses of biosynthetic genes for capsular
      polysaccharide, a well-documented virulence factor of Hi. We found mosaic
      sequences, linkage equilibrium between loci and a lack of congruence between gene
      trees. These high rates were not confined to LPS genes since evidence for similar
      amounts of recombination was also found in eight housekeeping genes in a subset
      of the same 25 isolates. These findings provide a population based foundation for
      a better understanding of the role of NTHi LPS as a virulence factor and its
      potential as a candidate vaccine.

PMID- 12797980
TI  - Metapopulation concepts applied to falciparum malaria and their impacts on the
      emergence and spread of chloroquine resistance.
AB  - Studying the structure of metapopulations is a new concept in population genetics
      of infectious diseases that is particularly adapted to the analysis of parasite
      populations. We considered one application of this theory focusing on Plasmodium
      falciparum populations. Our study consisted of three main steps: the relevance of
      the approach, the proposal of a simplified model using metapopulation concepts,
      and the exploration of the consequences on antimalarial drug resistance. Our main
      result concerns the metapopulation structure that is appropriate in some real
      situations. In intertropical rural Africa, parasite populations can be considered
      to be patchy, comparable to the panmictic situation in which a high transmission
      rate associated with a high prevalence (generally higher than 50%) implies that
      no diferenciation occurs between sub populations. In contrast, in Asia and South
      America, there are great variations in endemicity (with prevalences ranging from
      0 to 100%) consistent with a typical metapopulation dynamic structure and a high
      probability of differentiation between patches. These findings agree with the
      observed emergence of chloroquine resistance in south-east Asia and South
      American but not in Africa, and with its rapid spread following its introduction.

PMID- 12797979
TI  - Evidence for genetic exchange and hybridization in Trypanosoma cruzi based on
      nucleotide sequences and molecular karyotype.
AB  - Trypanosoma cruzi is thought to undergo predominant clonal evolution, as
      determined by population genetics studies. However, this model does not exclude
      occasional recombination, which existence is strongly suggested by several recent
      studies. We sequenced a portion of the maxicircle cytochrome b (CYb) gene and of
      the nuclear rRNA promoter region from representative strains of six T. cruzi
      genetic lineages isolated from anthroponotic environments and man (lineages IIb,
      IId and IIe), sylvatic environments (lineages IIa and IIc) or both (lineage I).
      Phylogenetic analyses based on the two genes were incongruent. Remarkably, in
      lineage IIe, CYb and rRNA sequences were very closely related to those of
      lineages IIc and IIb, respectively. One stock of lineage IId showed rRNA sequence
      heterogeneity, with both IIb-like and IIc-like copies. Analysis of the size
      variation of six distinct pairs of putative homologous chromosomes revealed a
      bimodal distribution of chromosomal sizes across T. cruzi. Notably, stocks of
      lineages IId and IIe had several chromosomal pairs distributed in distinct modes,
      with the corresponding modes individually found in lineages IIb and IIc.
      Together, these data indicate the origin of lineages IId and IIe by hybridization
      between representatives of lineages IIb and IIc. CYb and rRNA sequences clustered
      into three and four major lineages, respectively. Data were in agreement with the
      distinction of six genetic lineages, but not with their proposed grouping into
      two primary lineages, as lineage II was not monophyletic. Based on a CYb
      substitution rate of 1% per million years (Myr), the major lineages are estimated
      to have diverged around 10 million years ago.

PMID- 12797981
TI  - Genome sequence based, comparative analysis of the fluorescent amplified fragment
      length polymorphisms (FAFLP) of tubercle bacilli from seals provides molecular
      evidence for a new species within the Mycobacterium tuberculosis complex.
AB  - Tuberculosis in seals is caused by a member of the Mycobacterium tuberculosis
      complex referred to as the 'seal bacillus'. Fluorescent amplified-fragment length
      polymorphism (FAFLP) analysis was applied to isolates from four Australian and
      six Argentinean seals and compared with FAFLP pattern for standard strains
      belonging to the M. tuberculosis complex. The FAFLP profiles derived from
      EcoRI/MseI restricted fragments of blind coded DNA samples differentiated the
      seal bacillus from other members of the M. tuberculosis complex. According to the
      phylogenetic analysis performed using FAFLP data, seal bacilli appear to have
      diverged significantly from other members of the M. tuberculosis complex. We
      describe the suitability of a panel of 19 highly polymorphic markers for rapid
      identification and comparative genomic analyses of the seal bacillus strains. It
      is likely that these bacilli got separated from the M. tuberculosis lineage as a
      result of different insertion deletion events occurring on a genome wide scale.
      Our analysis reveals that the seal bacillus and M. bovis are genetically related
      and therefore, might have originated from a common ancestor. Our data
      additionally support the hypothesis that seal bacillus occupies a unique
      taxonomic position within the M. tuberculosis complex.

PMID- 12797982
TI  - Phylogenetic diversity of bat trypanosomes of subgenus Schizotrypanum based on
      multilocus enzyme electrophoresis, random amplified polymorphic DNA, and
      cytochrome b nucleotide sequence analyses.
AB  - Trypanosome stocks isolated from bats (Chiroptera) and belonging to the subgenus
      Schizotrypanum were analyzed by multilocus enzyme electrophoresis (MLEE) at 22
      loci, random amplified polymorphic DNA (RAPD) with 14 primers and/or cytochrome b
      nucleotide sequence. Bat trypanosomes belonged to the species Trypanosoma cruzi
      marinkellei (10 stocks), Trypanosoma dionisii (four stocks) and Trypanosoma
      vespertilionis (three stocks). One T. rangeli stock and seven stocks of T. cruzi
      sensu stricto, the agent of Chagas disease, were included for comparison. The
      homology of several RAPD fragments shared by distinct species was verified by
      hybridization. The sequence of a 516-nucleotide portion of the maxicircle-encoded
      cytochrome b (CYb) coding region was determined in representative stocks of the
      species under study. Phylogenetic analysis of the data confirmed the previous
      taxonomic attribution of these bat trypanosomes based on biological,
      epidemiological and ecological features. However, a new finding was that within
      T. cruzi marinkellei two major subdivisions could be distinguished, T.c.m. I,
      found in the spear-nose bats Phyllostomus discolor and Phyllostomus hastatus, and
      T.c.m. II, from P. discolor. In addition, the T. c. marinkellei 'Z' stock from a
      short-tailed bat (Carollia perspicillata) was distantly related to these two
      subdivisions, and the monophyly of T. c. marinkellei is unclear based on the
      present data. Based on the present sample, the European species T. dionisii and
      T. vespertilionis appeared to be more homogeneous. RAPD and CYb data both
      suggested the monophyly of a group composed of T. cruzi and the two major
      subdivisions of T. cruzi marinkellei. This study shows that MLEE, RAPD and CYb
      can be used for taxonomic assignment and provide valuable phylogenetic
      information for strains and taxa within the subgenus Schizotrypanum. An
      evolutionary scenario in which the broad host-range parasite T. cruzi would be
      derived from a bat-restricted trypanosome ancestor is discussed.

PMID- 12797985
TI  - Hidden Plasmodium falciparum parasites in human infections: different genotype
      distribution in the peripheral circulation and in the placenta.
AB  - Sequestration of the mature Plasmodium falciparum forms complicates detection,
      quantification and molecular analysis of human infections. Whether the
      circulating parasites represent all or only a subset of co-infecting genotypes is
      unclear. We have investigated this issue and compared placenta and peripheral
      blood msp1 and msp2 genotypes in 58 women delivering with an ICT-positive
      placenta in Guediawaye, Senegal. Most placenta (91%) and blood samples (98%) were
      multiply infected. Multiplicity of infection was positively correlated in both
      tissues. However, the placental and circulating genotype profiles differed
      markedly. Only 10% of matched peripheral blood/placenta samples had identical
      genotypes, whereas 74% had only partially concordant genotypes, with some alleles
      detected in both tissues, together with additional allele(s) detected in one
      tissue only. Eight women (14%) had totally discordant placental and peripheral
      blood genotypes. Thus, in the vast majority of cases, some sequestered genotypes
      remain hidden, undetected in the peripheral circulation, indicating that analysis
      of peripheral parasites generates a partial picture of a P. falciparum infection.

PMID- 12797984
TI  - Phylogeography of the neotropical sand fly Lutzomyia longipalpis inferred from
      mitochondrial DNA sequences.
AB  - Sand flies in the Lutzomyia longipalpis species complex include the primary
      vector of Leishmania chagasi, the etiologic agent of visceral leishmaniasis in
      the Neotropics. Twelve L. longipalpis populations from South and Central America
      were compared using the cytochrome c oxidase I (COI) gene from the mitochondrial
      genome. The haplotype profiles for each population revealed that the majority of
      sequence variation was inter-population (98%) rather than intra-population,
      suggesting that sequence polymorphisms at the COI locus should provide excellent
      characters for the study of phylogenetic relationships among populations.
      Phylogenetic reconstruction using distance (neighbor-joining) and maximum
      parsimony analysis revealed the existence of four clades among the L. longipalpis
      populations studied: (1) Laran, (2) Brazilian, (3) cis-Andean and (4) trans
      Andean. We suggest that these clades represent species. A biogeographical
      interpretation of the molecular phylogeny suggests that the process of speciation
      in the L. longipalpis complex began in the Pliocene, from a sub-Andean-Amazonian
      gene pool resulting from the Andean orogeny (formation of the East Andean
      Cordillera). The four clades probably diverged as a result of vicariance events
      that occurred throughout the late Pliocene and Pleistocene. We propose and
      discuss several historical scenarios, based on the biogeography and historical
      geology of Central and South America.

PMID- 12797986
TI  - Detection of Salmonella typhi by polymerase chain reaction: implications in
      diagnosis of typhoid fever.
AB  - The present study was conducted to detect Salmonella typhi by polymerase chain
      reaction (PCR) in a clinical setting. A group of 40 clinically suspected cases of
      typhoid fever, lasting for about 3-11 days, with or without chills and rigors and
      hepatosplenomegaly were selected. Of these, 20 were culture positive and the
      remaining 20 were found to be negative by conventional blood culture technique.
      Primary PCR was followed by nested PCR using two sets of primers corresponding to
      flagellar gene of S. typhi strain. Two bands of about 458 and 343 bp were
      detected in 20 blood culture positive cases and 12 of the 20 culture negative
      ones. In the simulated group of samples, no amplification was detected. Our
      results suggest that PCR-based diagnosis is particularly useful for all
      clinically suspected cases of typhoid fever. The sensitivity of PCR and its
      potential use in routine diagnosis and epidemiological studies of typhoid fever
      can be exploited to complement studies by including bone marrow culture, faeces
      and bile samples.

PMID- 12797987
TI  - Rhipicephalus ticks infected with Rickettsia and Coxiella in Southern Switzerland
      (Canton Ticino).
AB  - Ticks of the Rhipicephalus sanguineus species complex may be vector of various
      pathogens including Rickettsia conorii (the etiological agent of the
      Mediterranean spotted fever) and Coxiella burnetii (cause of the Query (Q)
      fever). R. sanguineus ticks have been imported in several parts of central and
      northern Europe, especially in environments such as kennels and houses providing
      the appropriate microclimatic conditions and the blood source necessary for their
      survival. Since 1940 these ticks have occasionally been recorded in Switzerland.
      In Ticino (the southern part of Switzerland), they have been reported since 1980
      and their probable establishment in this area has been suggested in the '90s. By
      means of PCR and direct sequencing, we tested the identity of these ticks (using
      12S rDNA gene) and the occurrence of Rickettsia spp. (using 16S rDNA, gltA and
      OmpA genes) as well as Coxiella sp. (using 16S rDNA). The results indicated that
      in Ticino, two different tick species coexist, i.e. R. sanguineus sensu stricto
      and Rhipicephalus turanicus. A few individuals of R. sanguineus sensu stricto are
      infected with Rickettsia massiliae/Bar29, which are strains of unknown
      pathogenicity. Coxiella sp., an endosymbiont of Rhipicephalus ticks, has also
      been identified in both tick species. Due to climatic changes towards global
      warming, imported tick species may therefore adapt to new area and might be
      considered as epidemiological markers for a number of infectious agents
      transmitted by them.

PMID- 12797988
TI  - Wing shape divergence between Rhodnius prolixus from Cojedes (Venezuela) and
      Rhodnius robustus from Merida (Venezuela).
AB  - The existence of Rhodnius robustus as a species distinct from Rhodnius prolixus
      has long been the main epidemiological question about Chagas disease transmission
      in Venezuela and surrounding countries. These two taxa are morphologically and
      genetically very similar, but only R. prolixus is assumed to colonize houses and
      transmit Chagas disease to humans. R. robustus is assumed to be an exclusively
      sylvatic species, restricted to palm trees. If robustus and prolixus are actually
      the same species, the theoretical possibility exists of sylvatic specimens
      invading houses, even after insecticide application, and a control strategy
      similar to that of the successful Southern Cone Initiative against Triatoma
      infestans would be difficult to consider. Since no valid alternative control
      strategy exists, the answer to this biological question could be decisive about
      the future of vector control in this region. Although we believe genetic
      techniques are best suited to define species boundaries, we present here an
      example of the relevance of modern morphometrics in dealing with such an issue.
      Using both traditional and geometric morphometrics, we compared the wing size and
      shape in both sexes of these two taxa reared in the same laboratory for one
      generation. R. robustus specimens were collected from palm trees in the state of
      Merida (Venezuela), and R. prolixus were collected from houses in the state of
      Cojedes (Venezuela). Our study provided no argument to question their specific
      status. Even after one generation of living in the same laboratory conditions,
      the two lines showed clear size differences, divergent allometric trends, and
      significant allometry-free differences in shape. These results suggest that R.
      robustus (Merida, Venezuela) and R. prolixus (Cojedes, Venezuela) are distinct
      evolutionary units. Due to the epidemiological importance of this question,
      further studies in other geographic areas of Venezuela are required to accurately
      define the relationships of R. robustus and R. prolixus.

PMID- 12797989
TI  - Several strains of Echinococcus granulosus infect livestock and humans in
      Argentina.
AB  - Mitochondrial cytochrome oxidase subunit 1 (CO1) sequencing, Southern blot of a
      repetitive DNA element and single strand conformation polymorphism of the 5' non
      transcribed region of the cytosolic malate dehydrogenase (MDH) gene were used to
      determine the extent and distribution of Echinococcus granulosus genetic
      variation in Argentina. Five distinct strains of E. granulosus were shown to
      exist in the country. The common sheep, Tasmanian sheep, cattle and camel strains
      were identified in humans. Unlike the situation found in other countries, where
      the common sheep strain is the major source of human contamination, the Tasmanian
      sheep and camel strains produced a significant number of human infections in some
      regions of Argentina. This is the first report of cattle strain in humans in
      South America. Goats could be the natural intermediate host of the camel strain,
      which was not identified in humans from other regions so far. More than one
      genotype was identified in the same geographic area. These findings may have
      important consequences for human health and the control of hydatid disease.
      Within-strain differences were also observed, showing the potential of variation
      of E. granulosus.

PMID- 12797990
TI  - r- and K-selection in experimental populations of vesicular stomatitis virus.
AB  - Here we explore the adaptation of vesicular stomatitis RNA virus to different
      population densities and the existence of a trade-off between r- and K-selection.
      Increasing population density represents a challenging special situation for
      viruses, since different selective pressures arise depending upon the number of
      available host cells per virus. Adaptation to low density represents a
      prototypical case of r-selection, where the optimal evolutionary solution should
      be a high replication rate. Adaptation to high density represents a case of K
      selection. In this case, genotypes optimally exploiting the resources, instead of
      faster replicating ones, should be selected. Five independent populations were
      maintained in two environments, called r and K, for 100 generations. In the r
      environment, effective population size was small. In contrast, the effective
      population size in the K environment was large. Our results support the existence
      of the expected trade-offs between these two types of selections. Viral
      populations evolved at low density performed worse as population density
      increased. Similarly, viral populations evolved at high density showed reduced
      fitness at low density. Finally, we compare our results with those obtained for
      other RNA viruses.

PMID- 12797991
TI  - Poor value of pulsed-field gel electrophoresis to investigate long-term scale
      epidemiology of methicillin-resistant Staphylococcus aureus.
AB  - Pulsed-field gel electrophoresis (PFGE) is widely used for epidemic
      investigations of methicillin-resistant Staphylococcus aureus (MRSA). In the
      present study, we evaluated its use in a long-term epidemiological setting (years
      to few decades, country to continent level). The clustering obtained from PFGE
      patterns after SmaI digestion of the DNA of 20 strains was compared to that
      obtained using a phylogenetic typing method (multiprimer RAPD). The results
      showed that the analysis of small PFGE bands (10-85kb) correlates better with
      multiprimer RAPD than the analysis of large PFGE bands (>85-700kb), suggesting
      that the analysis of small bands would be more suitable for the investigation of
      long-term epidemiological setting. However, given the technical difficulties to
      obtain a good resolution of these bands and the putative presence of plasmids
      among them, PFGE does not appear to be a method of choice for the long-term
      epidemiology analysis of MRSA.

PMID- 12797992
TI  - Further difficulties with multifactorial analysis of variance: random and nested
      factors and independence of data.

PMID- 12797993
TI  - Molecular epidemiology of Mycobacterium tuberculosis and its relevance to the
      surveillance and control of TB: an e-debate.

PMID- 12797996
TI  - Evolution of inhibitors of apoptosis in baculoviruses and their insect hosts.
AB  - The phylogenetic relationships of inhibitor of apoptosis (IAP) from insects and
      insect viruses were reconstructed and compared with the phylogeny of the viruses
      reconstructed on the basis of DNA polymerase species. The phylogeny supported the
      hypothesis that there were three IAP genes in the ancestor of the viral genus
      Nucleopolyhedrovirus (family Baculoviridae), but that there has been differential
      deletion of IAP genes in different lineages within this genus. An IAP gene from
      the granulovirus of the lepidopteran species Cydia pomonella (CpGV) was found to
      be a close relative of IAP genes from species of the insect order Lepidoptera,
      supporting the origin of this viral gene by capture of a host gene early in the
      evolution of Lepidoptera. The phylogeny supported the occurrence of least one
      other independent event of capture of an IAP gene by a virus and suggested the
      possibility of at least two other such events. Contrary to the prediction that
      host genes with viral homologues should experience an enhanced rate of amino acid
      replacement, no acceleration of evolutionary rate was detectable in these
      lepidopteran genes, which showed particularly low rates of non-synonymous
      nucleotide substitution in functionally important domains.

PMID- 12797997
TI  - Phylogenetic relationships within the oliveirai complex
      (Hemiptera:Reduviidae:Triatominae).
AB  - The oliveirai complex is actually composed of nine related species of Triatominae
      that occur in the Pantanal ecosystem of Mato Grosso, Brazil. In order to confirm
      their specific status and infer their phylogenetic relationships, we performed a
      genetic and morphometric comparison concerning seven of the nine species of the
      complex. Isoenzyme analysis provided broadly similar phylogenetic information to
      that derived from discriminant analysis of size-free variables. The derived trees
      reveal two main species groups, one composed of three closed species (T.
      jurbergi, T. matogrossensis and T. vandae), and another one subdivided into two
      different pairs, the T. guazu-T. williami pair and the T. klugi-T. oliveirai
      pair. The results call the specific status of T. guazu and T. williami into
      question, support the possibility that the other analyzed species represent
      distinct taxa and query the existence of the oliveirai complex.

PMID- 12797998
TI  - Microevolutionary changes and chromosomal translocations are more frequent at RPS
      loci in Candida dubliniensis than in Candida albicans.
AB  - The Cd1 fingerprinting probe of Candida dubliniensis, which is extremely
      effective in identifying microevolutionary changes in infecting populations,
      generates hybridization patterns that are similar to those generated by the
      Candida albicans fingerprinting probe Ca3. Since Ca3 recognizes microevolutionary
      changes through the repeat sequence RPS, it was suggested that Cd1 also contains
      a RPS-like element. To test this possibility, the C. albicans RPS unit was used
      as a probe, and an RPS-like element, RPSd1, was cloned from C. dubliniensis. The
      sequence of RPSd1 was 76% homologous to that of the C. albicans RPS unit RPS620
      and the organization, including the non-RPS 3' and 5' bordering sequences, was
      highly similar. This analysis revealed additional copies of the repeat extraalt
      element and short additional repeat (SAR) sequences in both RPSd1 and RPS620 not
      previously identified in the latter. This analysis has allowed us to develop a
      model of RPSd1 organization and to revise the model for RPS620 organization. An
      estimate of the average frequency of reorganization (duplication and deletion)
      per RPS unit in C. dubliniensis was similar to that for C. albicans, but the
      estimate of frequency of reorganization per C. dubliniensis genome was higher,
      most probably as a result of the higher estimated average number of RPS clusters
      in C. dubliniensis. These results demonstrate that the microevolutionary changes
      identified by the Cd1 fingerprinting probe are based on the reorganization of RPS
      like elements and are, therefore, similar to the microevolutionary changes
      identified by the Ca3 probe of C. albicans. Linkage analysis of pairs of markers
      situated on either side of an RPS cluster on chromosome 7 further revealed
      frequent recombination between non-homologous chromosomes at the RPS cluster in
      C. dubliniensis strains, but not in C. albicans strains, suggesting that RPS
      clusters may function as recombination hot spots in C. dubliniensis.

PMID- 12797999
TI  - Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000
      years old.
AB  - A global collection of 26 isolates of Salmonella typhi was investigated by
      sequencing a total of 3336 bp in seven housekeeping genes. Only three polymorphic
      sites were found and the isolates fell into four sequence types. These results
      show that S. typhi is a recent clone whose last common ancestor existed so
      recently that multiple mutations have not yet accumulated. Based on molecular
      clock rates for the accumulation of synonymous polymorphisms, we estimate that
      the last common ancestor of S. typhi existed 15,000-150,000 years ago, during the
      human hunter-gatherer phase and prior to the development of agriculture and the
      domestication of animals.

PMID- 12798000
TI  - Chromosomal evolution trends of the genus Panstrongylus (Hemiptera, Reduviidae),
      vectors of Chagas disease.
AB  - The genus Panstrongylus includes 14 species widely distributed from Mexico to
      Argentina, some of them with great epidemiological significance as vectors of
      Chagas disease. We study the karyotype and the male meiotic process of
      Panstrongylus chinai, P. geniculatus, P. herreri, P. lignarius, P. megistus, P.
      rufotuberculatus and P. tupynambai. All species present the same sex mechanism
      (X(1)X(2)Y in males and X(1)X(1)X(2)X(2) in females) and they also have 20
      autosomes, with the exception of P. megistus that only presents 18 autosomes. The
      analysis of C-banding patterns and meiotic chromosome behaviour show a great
      level of variability allowing the identification of three clearly differentiated
      groups. In the first group, we only include P. megistus because of its unusual
      number of autosomes. The second group includes P. chinai, P. herreri, P.
      lignarius and P. rufotuberculatus. Their autosomes present terminal
      heterochromatic regions that appear scattered throughout the nucleus and
      associated with the sex chromosomes. Actually, P. herreri and P. lignarius can be
      considered cytogenetically identical. Our results are in agreement with
      morphological, ecological and molecular data indicating that they should be
      regarded as the same species. The third group only includes P. tupynambai that
      shows autosomes without C-positive regions. Panstrongylus geniculatus shares
      characters will all the three groups. Its karyotypic features are extremely
      polymorphic depending on their geographic origin. Some populations do not show
      any heterochromatic regions, while others exhibit few or several heterochromatic
      blocks. The chromosomal variability observed, together with its wide distribution
      and phenetic variability, suggest that P. geniculatus is a species complex
      comprising at least two distinct species. Considering the entire subfamily, the
      level of cytogenetic variation in Panstrongylus is lower than that observed in
      Triatoma but considerably more than that of Rhodnius, which is a very homogenous
      genus in terms of chromosome appearance and behaviour. This would endorse the
      closer relationship between Panstrongylus and Triatoma, and their divergence from
      Rhodnius, in accordance with current tribal classification.

PMID- 12798001
TI  - Population structure of Candida albicans, a member of the human flora, as
      determined by microsatellite loci.
AB  - This study examines the macrogeographic population structure of Candida albicans,
      a yeast commensal of humans, through a population genetic analysis of 5
      microsatellite loci in 13 cities. The populations were predominantly clonal with
      some recombination. About 5% of the genetic variation is between populations and
      the overall pattern is one of intermediate differentiation. We did not find a
      single widespread genotype but instead found high, macrogeographic gene flow in
      these clinical populations; the most common genotype was limited to Atlanta and
      San Francisco. Homogeneity is evident within large geographic regions, such as
      Europe, Asia, and the USA, and isolation by distance accounted for 39% of the
      variation observed. Overall gene flow for a member of the human flora is variable
      but can be extensive, with an average of 4.5 migrants per generation (N(m)).
      Eastern hemisphere populations were less divergent than those of the Americas and
      Caribbean, consistent with the expansion of humans out of the eastern hemisphere.

PMID- 12798002
TI  - Morphological variability in the malaria vector, Anopheles moucheti, is not
      indicative of speciation: evidences from sympatric south Cameroon populations.
AB  - Anopheles moucheti is a major human malaria vector in the vicinity of slow moving
      rivers in the tropical forests of Central Africa. Morphological variations in
      natural populations of A. moucheti led to the designation of three morphological
      forms named A. moucheti moucheti, A. moucheti nigeriensis and A. moucheti
      bervoetsi. Using allozyme markers, we investigated to which extent morphological
      and/or geographical populations of A. moucheti were genetically differentiated.
      Mosquitoes were collected from four villages 20-200 km distant apart in south
      Cameroon, where specimens from each morphological form were found in sympatry.
      All populations appeared highly homogenous across both morphological type and
      geographic location. Significant genetic differentiation was only observed
      between two locations 150 km apart (F(st)=0.029; P=0.006), while no pairwise
      F(st) estimate between morphological forms reached statistical significance.
      Further evidence against any taxonomic value of this morphological classification
      was provided by direct observation of morphological variation within the progeny
      of field-collected females from all three types. Single female offspring always
      belonged to at least two morphologically recognised types and most often, a
      mixture of all three forms was observed. Our results therefore demonstrate that
      morphological variability within A. moucheti natural populations is not
      indicative of speciation. With this respect, restricted migration of individuals
      across river systems may be a more important factor in shaping population genetic
      structure of A. moucheti.

PMID- 12798003
TI  - Optimization of random amplified polymorphic DNA techniques for its use in
      genetic studies of Trichomonas vaginalis isolates.
AB  - The random amplified polymorphic DNA (RAPD) technique is a simple method to
      detect DNA polymorphism. Several factors can affect the amplification profiles
      causing the presence of false bands and assay non-reproducibility. In this study,
      we analyzed the effect of changing concentrations of the primer, template DNA and
      Taq DNA polymerase with the goal of determining their optimum concentration for
      the standardization of the RAPD technique for genetic studies of Trichomonas
      vaginalis, a parasite that is of major epidemiological relevance in Cuba.

PMID- 12798004
TI  - Basic vs. applied research, field vs. bench work: the never-ending dialogues of
      the deaf.

PMID- 12798005
TI  - Clonal diversity of Shiga toxin-producing Escherichia coli O103:H2/H(-) in
      Germany.
AB  - Shiga toxin producing Escherichia coli O103:H2/H(-) belong to the third most
      frequently isolated EHEC serotypes in Germany following isolates of O157:H7/H(-)
      and O26:H11/H(-). A total of 145 respective E. coli 103 isolates from single
      cases of diarrhoea and haemolytic uremic syndrome (HUS) in 1997-2000 were
      characterised by a range of molecular subtyping methods (PFGE, P-gene profiling,
      ribotyping, electrotyping) and phage typing in order to analyse their genetic
      relatedness and the practicability for new epidemiological tracing back. All
      isolates cluster into a distinct EHEC subgroup and reveal a high clonal diversity
      together with a considerable stability. Since strains of this serotype rank up to
      the third most frequently isolated EHEC in Germany a large population of this
      serotype, and therefore, a great supply of such strains may exist in this
      country.

PMID- 12798007
TI  - Virulence in rodent malaria: host genotype by parasite genotype interactions.
AB  - In an effort to understand what limits the virulence of malaria parasites, we
      infected inbred mice of three genotypes (C57Bl/6J, CBA/Ca and DBA/2) with one of
      two parasite lines of the rodent malaria Plasmodium chabaudi. One of these
      parasite lines had been serially passaged through C57Bl/6J mice and had evolved
      higher asexual growth rate, virulence and transmission in the process. The other
      parasite line was the unadapted ancestral line which had low virulence. In all
      three host genotypes, the C57Bl/6J-adapted parasite line was more virulent than
      the ancestral line thus indicating that trade-offs in virulence between
      alternative host genotypes had not placed strong constraints on the evolution of
      high virulence in this system. By examining the infection dynamics for fitness
      related components-asexual parasite population growth, transmission and virulence
      we revealed alternative possible explanations for what sets the upper limit to
      virulence in nature. The total number of transmission forms (gametocytes)
      produced during the infection, a measure of parasite Darwinian fitness, was four
      fold higher in mice that survived the infection than those which died. Among mice
      that survived, total gametocyte production was greatest in the host genotype that
      suffered intermediate levels of morbidity (anaemia and weight loss). Thus, there
      were transmission costs of high virulence that were partly due to host death (as
      most theoretical models of virulence evolution assume), but perhaps partly due to
      some factor related to high morbidity. Both mortality and morbidity-related
      factors might therefore influence the upper limit on virulence of malaria
      parasites.

PMID- 12798006
TI  - Recombination in Mycoplasma hominis.
AB  - Mycoplasma hominis has been previously described as a heterogeneous species, and
      in the present study intraspecies diversity of 20 M. hominis isolates from
      different individuals was analyzed using parts of the unlinked gyrase B (gyrB),
      elongation factor Tu (tuf), SRalpha homolog (ftsY), hitB-hitL, excinuclease ABC
      subunit A (uvrA) and glyceraldehyde-3-phosphate dehydrogenase (gap) genes. The
      level of variability of these M. hominis genes was low compared with the
      housekeeping genes from Helicobacter pylori and Neisseria meningitidis, but only
      few M. hominis isolates had identical sequences in all genes indicating the
      presence of recombination. In order to test for intergenic recombination,
      phylogenetic trees were reconstructed for each of the genes but no well-supported
      bifurcating phylogenetic trees could be obtained. The genes were tested for
      intragenic recombination using the correlation between linkage disequilibrium and
      distance between the segregating sites, by the homoplasy ratio (H ratio), and by
      compatibility matrices. The gap gene showed well-supported evidence for high
      levels of recombination, whereas recombination was less frequent and not
      significant within the other genes. The analysis revealed intergenic and
      intragenic recombination in M. hominis and this may explain the high intraspecies
      variability. The results obtained in the present study may be of importance for
      future population studies of Mycoplasma species.

PMID- 12798008
TI  - Phylogenetic analysis of the genus Plasmodium based on the gene encoding
      adenylosuccinate lyase.
AB  - Phylogenetic studies of the genus Plasmodium have been performed using sequences
      of the nuclear, mitochondrial and plastid genes. Here we have analyzed the
      adenylosuccinate lyase (ASL) gene, which encodes an enzyme involved in the
      salvage of host purines needed by malaria parasites for DNA synthesis. The ASL
      gene is present in several eukaryotic as well as prokaryotic organisms and does
      not have repeat regions, which facilitates the accuracy of the alignment.
      Furthermore, it has been shown that ASL is not subject to positive natural
      selection. We have sequenced the ASL gene of several different Plasmodium species
      infecting humans, rodents, monkeys and birds and used the obtained sequences
      along with the previously known P. falciparum ASL sequence, for structural and
      phylogenetic analysis of the genus Plasmodium. The genetic divergence of ASL is
      comparable with that observed in other nuclear genes such as cysteine proteinase,
      although ASL cannot be considered conserved when compared to aldolase or
      superoxide dismutase, which exhibit a slower rate of evolution. Nevertheless, a
      protein like ASL has a rate of evolution that provides enough information for
      elucidating evolutionary relationships. We modeled 3D structures of the ASL
      protein based on sequences used in the phylogenetic analysis and obtained a
      consistent structure for four different species despite the divergence observed.
      Such models would facilitate alignment in further studies with a greater number
      of plasmodial species or other Apicomplexa.

PMID- 12798009
TI  - Inappropriate application of a model for mixed analysis of variance: some
      comments on Elena et al. (2001).

PMID- 12798011
TI  - INSERM fosters researches on infectious diseases.

PMID- 12798012
TI  - Basic research: what is it good for AIDS epidemiology and control?. An e-debate.

PMID- 12798013
TI  - The European Centre for Infectious Diseases: an adequate response to the
      challenges of bioterrorism and major natural infectious threats.

PMID- 12798014
TI  - A point mutation in codon 76 of pfcrt of P. falciparum is positively selected for
      by Chloroquine treatment in Tanzania.
AB  - This study was undertaken to validate the relevance of Chloroquine (CQ)
      resistance markers pfcrt(76) and pfmdr1(86) in an endemic area in Tanzania. After
      treatment with CQ, recrudescence was distinguished from new infection by msp2
      genotyping, and the number of concurrent infections was also determined. The rate
      of children with recrudescent parasites at day 7 and/or day 14 amounted to a
      parasitological failure rate of 22.4% using PCR. The mean multiplicity of
      infection at day 0 was 3.2 (n=71). The allelic frequencies of the mutated
      pfcrt(76) and pfmdr1(86) were estimated to be 92 and 77%, respectively. Both
      values exceeded by far the observed frequency of 14% of recrudescent parasites as
      calculated on the whole analysed parasite population taking multiple infections
      into account. Although neither mutant allele is of predictive value for
      parasitological resistance, there is evidence for a role of pfcrt(76) in CQ
      resistance in the natural parasite population. All wild-type pfcrt(76) alleles
      were eliminated before day 3, after the onset of CQ treatment and no recrudescent
      parasite with the wild-type allele was observed at later time points. The
      discrepancy between the rate of resistant parasites (14%) and the frequency of
      the mutant pfcrt(76) allele (92%), however, indicates that other polymorphisms
      and other factors must be involved in CQ resistance. No selective elimination of
      the pfmdr1(86) wild-type allele was observed.

PMID- 12798015
TI  - Natural nidality in Bolivian hemorrhagic fever and the systematics of the
      reservoir species.
AB  - Zoonoses within wild reservoir host populations often occur focally obeying
      Pavlovskii's rules of "natural nidality". What appears to be a clear example is
      Bolivian hemorrhagic fever (BHF), a disease endemic to northeastern Bolivia. The
      etiological agent is Machupo virus (MACV, Arenaviridae). The vertebrate
      reservoir, identified 30 years ago, was Calomys callosus a wild rodent common to
      open biomes in the lowlands of southeastern South America. The lack of
      concordance between the occurrence of MACV and the range of its rodent host has
      puzzled cadres of researchers and could be used as an exemplar of natural
      nidality. Here, we show that the populations of rodents responsible for the
      maintenance and transmission of MACV are an independent monophyletic lineage,
      different from those in other areas of South America. Therefore a clearer
      understanding of the systematics of the host species explains the apparent
      natural nidality of BHF. Similar studies may prove to be informative in other
      zoonoses.

PMID- 12798016
TI  - Frequencies of 32 base pair deletion of the (Delta 32) allele of the CCR5 HIV-1
      co-receptor gene in Caucasians: a comparative analysis.
AB  - The CCR5 gene encodes for the co-receptor for the major macrophage-tropics
      strains of human immunodeficiency virus (HIV-1), and a mutant allele of this gene
      (Delta 32) provide to homozygotes a strong resistance against infection by HIV.
      The frequency of the Delta 32 allele was investigated in 40 populations of 8842
      non-infected subjects coming from Europe, the Middle-East and North Africa. A
      clear north-south decreasing gradient was evident for Delta 32 frequencies, with
      a significant correlation coefficient (r=0.83). The main frequency value of Delta
      32 for Sweden, Norway, Denmark, Finland and Iceland (0.134) is significantly
      (chi(2)=63.818, P<0.001) highest than the Delta 32 mean value, indicating that
      probably the Vikings might have been instrumental in disseminating the Delta 32
      allele during the eighth to the tenth centuries during historical times. Possibly
      variola virus has discriminated the Delta 32 carriers in Europe since the eighth
      century AD, explaining the high frequency of the Delta 32 allele in Europe today.

PMID- 12798017
TI  - The human serum resistance associated gene is ubiquitous and conserved in
      Trypanosoma brucei rhodesiense throughout East Africa.
AB  - The human serum resistance associated (SRA) gene isolated from a Ugandan strain
      of Trypanosoma brucei rhodesiense has been shown to be capable by itself of
      conferring the trait of human infectivity on T.b. brucei by transfection. This
      gene has also been identified in several other isolates of T.b. rhodesiense, but
      not in the other human pathogenic trypanosome in Africa, T.b. gambiense, casting
      doubt on its ubiquity and function. Here, we show that this gene occurs in T.b.
      rhodesiense from sleeping sickness foci throughout East Africa (Ethiopia, Uganda,
      Kenya, Tanzania, Zambia, Botswana), but is not found in T.b. brucei isolates or
      any other trypanosomes of subgenus Trypanozoon. SRA genes from 10 T.b.
      rhodesiense isolates from five disease foci were compared and were 97.9-99.7%
      homologous, with three minor sequence variants. PCR amplification of this gene
      forms the basis of a new test to identify T.b. rhodesiense. This is the first
      molecular marker identified for T.b. rhodesiense, despite intensive efforts over
      the past 20 years. It will be invaluable for identification of animal reservoir
      hosts and detection of T.b. rhodesiense in its tsetse fly vector. Strain typing
      using minisatellite markers showed considerable genetic heterogeneity between
      T.b. rhodesiense isolates, despite the presence of the conserved SRA gene. These
      results are consistent with the hypothesis that new T.b. rhodesiense strains
      arise by genetic exchange among T. brucei ssp. spreading the SRA gene and thereby
      the trait for human serum resistance and human infectivity.

PMID- 12798018
TI  - Helicobacter: molecular phylogeny and the origin of gastric colonization in the
      genus.
AB  - The proteobacterial genus Helicobacter is composed of gastric species, all of
      them urease-positive, and enteric species (gastrointestinal, intestinal, hepatic,
      biliary), some of them urease-positive, others not. Here, we point out that the
      gastric species are divided in at least two phylogenetic groups, one is
      homogeneous, clearly separated from the enteric species, and another is forming a
      tight cluster within the enteric species. This feature is apparent in the
      phylogeny of the genus as inferred from both the 16S rRNA gene and the alpha
      subunit of the urease. Our observation shows that the ability to colonize the
      gastric mucosa appeared more than once in the history of the genus, and suggests
      that acquiring this ability may be a relatively simple and punctual process,
      involving a limited number of genes. Such a process may be the lateral transfer
      acquisition of a functional copy of the gene ureI which encodes a urea channel
      activated at acidic pH that is essential for gastric colonization by Helicobacter
      pylori.

PMID- 12798020
TI  - Whole genome fingerprinting and genotyping of multiple drug resistant (MDR)
      isolates of Pseudomonas aeruginosa from endophthalmitis patients in India.
AB  - Genome sequence-based fluorescent amplified-fragment length polymorphism (FAFLP)
      analysis was investigated for fingerprinting and subtyping 42 multiple drug
      resistant (MDR) isolates of Pseudomonas aeruginosa from post-surgical
      endophthalmitis. The FAFLP profiles derived from EcoRI/MseI restricted fragments
      differentiated clinical isolates and were found to be extremely reproducible.
      Seventeen different amplification patterns (amplitypes) were observed for all the
      42 isolates from 11 different patients. Also, we were able to genotype the
      isolates based on the differential amplification of a total of 31 FAFLP markers
      representing genomic fragments from the P. aeruginosa chromosome. This data
      appears to provide clues to the genetic diversity of endopthalmitis associated
      strains and could be converted into digitised fingerprints suitable for
      electronic manipulations and archiving.

PMID- 12798019
TI  - Nuclear rDNA ITS-2 sequences reveal polyphyly of Panstrongylus species
      (Hemiptera: Reduviidae: Triatominae), vectors of Trypanosoma cruzi.
AB  - Panstrongylus species are widely distributed throughout the Americas, where they
      act as vectors of Trypanosoma cruzi, agent of Chagas disease. Their intraspecific
      relationships, taxonomic position and phylogeny in relation to other Triatomini
      were explored using ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS-2)
      sequence polymorphisms and maximum parsimony, distance and maximum likelihood
      analyses of 10 populations representing six species of the genus (P. megistus, P.
      geniculatus, P. rufotuberculatus, P. lignarius, P. herreri and P. chinai). At the
      subspecific level, P. megistus appeared more homogeneous than P. rufotuberculatus
      and P. geniculatus (both with broader distribution). Several dinucleotide
      microsatellites were detected in the sequences of given species. Many of these
      microsatellites (GC, TA, GT and AT) showed different number of repeats in
      different populations and thus, may be very useful for population differentiation
      and dynamics analyses in future studies. The sequences of P. lignarius
      (considered sylvatic) and P. herreri (a major disease vector in Peru) were
      identical, suggesting that these species should be synonymised. Intrageneric
      analysis showed a clear separation of P. rufotuberculatus, with closest
      relationships between P. geniculatus and P. chinai, and P. megistus occupying a
      separate branch. Genetic distances between Panstrongylus species (0.11585
      0.22131) were higher than those between Panstrongylus and other Triatomini (16
      species from central and North America and South America) (0.08617-0.11039). The
      distance between P. megistus and P. lignarius/herreri (0.22131) was the largest
      so far recorded in the tribe. The pronounced differences in length and nucleotide
      composition suggest a relatively old divergence of Panstrongylus species. P.
      rufotuberculatus was closer to Mesoamerican Triatoma, Meccus and Dipetalogaster
      species than to other Panstrongylus. All Panstrongylus clustered with the
      Mesoamerican clade; P. rufotuberculatus clustered with the phyllosoma complex and
      T. dimidiata, with D. maxima and T. barberi in a basal position. The rest of
      Panstrongylus appeared paraphyletically in the tree. This is evidence suggesting
      polyphyly within the genus Panstrongylus, whose species may be related to the
      ancestors giving rise to central and North American Triatomini.

PMID- 12798021
TI  - Identification and characterization of microsatellite markers in the Chagas
      disease vector Triatoma dimidiata.
AB  - Triatoma dimidiata, one of the major vectors of Chagas disease in Central
      America, is found in both domestic and peri-domestic habitats. Questions
      concerning population boundaries, infestation rates, insecticide resistance, and
      geographic dispersal of triatomine bugs persist and may be resolved using genetic
      markers such as microsatellites. Microsatellites are short tandem repeats found
      dispersed throughout a genome and can be useful for genotypic identification. We
      developed a plasmid library from the genomic DNA isolated from a single T.
      dimidiata adult collected in Guatemala. Ten thousand clones were screened using a
      probe consisting of nine microsatellite oligonucleotides. Eight loci appear
      polymorphic among populations found in Guatemala, Honduras, and Mexico, and thus
      are potentially useful for population genetic applications.

PMID- 12798023
TI  - The golden age of genetics?

PMID- 12798022
TI  - 2002 Neodarwinism and infectious diseases transmission: an e-debate.

PMID- 12798024
TI  - European Lymnaeidae (Mollusca: Gastropoda), intermediate hosts of trematodiases,
      based on nuclear ribosomal DNA ITS-2 sequences.
AB  - Freshwater snails of the family Lymnaeidae are of a great parasitological
      importance because of the very numerous helminth species they transmit, mainly
      trematodiases of large medical and veterinary impact. The present knowledge on
      the genetics of lymnaeids and on their parasite-host inter-relationships is far
      from being sufficient. The family is immersed in a systematic-taxonomic
      confusion. The necessity for a tool which enables species distinction and
      population characterization is evident. This paper aims to review the European
      Lymnaeidae basing on the second internal transcribed spacer ITS-2 of the nuclear
      ribosomal DNA. The ITS-2 sequences of 66 populations of 13 European and 1 North
      American lymnaeid species, including the five generic (or subgeneric) taxa
      Lymnaea sensu stricto, Stagnicola, Omphiscola, Radix and Galba, have been
      obtained. The ITS-2 proves to be a useful marker for resolving supraspecific,
      specific and population relationships in Lymnaeidae. Three different groupings
      according to their ITS-2 length could be distinguished: Radix and Galba may be
      considered the oldest taxa (370-406 bp lengths), and Lymnaea s. str., European
      Stagnicola and Omphiscola (468-491 bp lengths) the most recent, American
      Stagnicola and Hinkleyia being intermediate (434-450 bp lengths). This hypothesis
      agrees with the phylogeny of lymnaeids based on palaeontological data, chromosome
      numbers and radular dentition. ITS-2 sequences present a conserved central region
      flanked by two variable lateral regions corresponding to the 5' and 3' ends. The
      number of repeats of two microsatellites found in this conserved central region
      allows to differentiate Radix from all other lymnaeids. Phylogenetic trees showed
      four clades: (A) Lymnaea s. str., European Stagnicola and Omphiscola; (B) Radix
      species; (C) Galba truncatula; and (D) North American stagnicolines. ITS-2
      results suggest that retaining Stagnicola as a subgenus of Lymnaea may be the
      most appropriate and that genus status for Omphiscola is justified. Radix shows a
      complexity suggesting different evolutionary lines, whereas G. truncatula appears
      to be very homogeneous. North American and European stagnicolines do not belong
      to the same supraspecific taxon; the genus Hinkleyia may be used for the American
      stagnicolines. Genetic distances and sequence differences allowed us to
      distinguish the upper limit to be expected within a single species and to how
      different sister species may be. S. palustris, S. fuscus and S. corvus proved to
      be valid species, but S. turricula may not be considered a species independent
      from S. palustris. Marked nucleotide divergences and genetic distances detected
      between different S. fuscus populations may be interpreted as a process of
      geographic differentiation developping in the present. Among Radix, six valid
      species could be distinguished: R. auricularia, R. ampla, R. peregra (=R.
      ovata;=R. balthica), R. labiata, R. lagotis and Radix sp. The information which
      the ITS-2 marker furnishes is of applied interest concerning the molluscan host
      specificity of the different trematode species. The phylogenetic trees inferred
      from the ITS-2 sequences are able to differentiate between lymnaeids transmitting
      and those non-transmitting fasciolids, as well as between those transmitting F.
      hepatica and those transmitting F. gigantica. The Fasciola specificity is linked
      to the two oldest genera which moreover cluster together in the phylogenetic
      trees, suggesting an origin of the Fasciola ancestors related to the origin of
      this branch. European Trichobilharzia species causing human dermatitis are
      transmitted only by lymnaeids of the Radix and Lymnaea s. str.-Stagnicola groups.
      Results suggest the convenience of reinvestigating compatibility differences
      after accurate lymnaeid species classification by ITS-2 sequencing. Similarly,
      ITS-2 sequencing would allow a step forward in the appropriate rearrangement of
      the actual systematic confusion among echinostomatids.

PMID- 12798025
TI  - Typing of drug resistant isolates of Mycobacterium tuberculosis from India using
      the IS6110 element reveals substantive polymorphism.
AB  - We investigated IS6110 polymorphism in clinical isolates of Mycobacterium
      tuberculosis from patients attending the outpatient department at various
      hospitals in northern India. DNA fingerprinting of 126 clinical isolates of M.
      tuberculosis was carried out using restriction fragment length polymorphism
      (RFLP) associated with the IS6110 element in M. tuberculosis genomes. A
      substantive degree of polymorphism was evident in the MDR M. tuberculosis
      isolates. The number of bands in the fingerprints varied from 0 to 19. However,
      the lack of common bands made it difficult to cluster the majority of these
      isolates. We were also unable to associate drug resistance with IS6110 copy
      number. Specific regions of the gyrA and katG genes from a representative number
      of these isolates were sequenced to determine the genotype. The majority of the
      isolates analyzed were found to belong to Group 1, indicating that these strains
      were evolutionarily older. We find no evidence of the W strain, prevalent in the
      US, in our study. The epidemiological patterns of the various strains in India
      seem to be very complex, as reflected by the presence of a large number of
      different strains (types) within north India.

PMID- 12798026
TI  - The population structure of Neisseria meningitidis serogroup A fits the
      predictions for clonality.
AB  - The population structure of Neisseria meningitidis is supposedly epidemic
      according to. The model predicts that linkage disequilibrium in N. meningitidis
      populations is only temporary and arises due to the outgrowth of highly
      successful clonal genotypes from an essentially sexual population. These clones
      should disappear after a few years because of frequent recombination. In
      contrast, multilocus enzyme electrophoresis (MLEE) data had previously been
      interpreted as showing that serogroup A meningococci are truly clonal and possess
      only limited genetic variability (Wang et al., 1992). The two interpretations are
      contradictory. In order to elucidate the true population structure of serogroup A
      meningococci, we analyzed data for a representative group of 84 serogroup A
      isolates obtained by MLEE, random amplified polymorphic DNA (RAPD) and multilocus
      sequence typing (MLST). Analysis of linkage disequilibrium and bootstrap analyses
      of cluster analysis showed a strongly structured population with highly
      significant linkage disequilibrium. This was not due to the overrepresentation of
      certain genotypes, in contrast to the expectations for an epidemic population.
      The analyses identify two main clades, within each of which linkage
      disequilibrium was also highly significant, thus, excluding a cryptic speciation
      model. These observations support a population structure based on clonal
      evolution, in which clones are much more stable than expected for epidemic
      clonality. We propose that serogroup A meningococci may possess a different
      population structure from other serogroups of Neisseria meningitidis.

PMID- 12798027
TI  - Evolutionary change of predicted cytotoxic T cell epitopes of dengue virus.
AB  - Peptides bound by human class I major histocompatibility complex molecules and
      presented to cytotoxic T cells (CTL) were predicted by a computer algorithm, and
      changes in these predicted CTL epitopes (pCTLE) were reconstructed by maximum
      parsimony in a phylogeny of complete genotypes of dengue virus, West Nile virus
      (WNV), and Japanese encephalitis virus (JEV). In a clade including dengue virus
      serotypes 1 and 3 (D1V and D3V), pCTLE were lost over evolutionary time at a
      greater rate than new ones were gained. A similar but less pronounced trend was
      seen in the other dengue serotypes but not in WNV and JEV. The loss of pCTLE
      predicted to be restricted by HLA-B(*)2705 was particularly pronounced in D1V and
      D3V. Since dengue is endemic in humans, while WNV and JEV are not, these results
      are consistent with CTL-driven selection on dengue viruses, particularly, D1V and
      D3V.

PMID- 12798028
TI  - The role of As60A, a TGF-beta homolog, in Anopheles stephensi innate immunity and
      defense against Plasmodium infection.
AB  - We have examined the constitutive and induced expression of As60A in Anopheles
      stephensi females. As60A is expressed throughout the body of A. stephensi,
      including the midgut, fat body and developing eggs. We discovered that As60A is
      induced in the midgut and carcass of A. stephensi in response to Plasmodium
      infection. Induction of As60A correlates with periods of parasite motility and
      reproduction. Further, induction is dependent on the intensity of parasite
      infection: low numbers of parasites do not induce As60A expression. Thus, we
      conclude that As60A is a component of the A. stephensi immune response to
      Plasmodium infection. The involvement of a member of the transforming growth
      factor beta (TGF-beta) super family in the mosquito immune response is analogous
      to the involvement of TGF-beta1 in the mammalian immune response to Plasmodium.
      The modulation of As60A and A. stephensi nitric oxide synthase (AsNOS) expression
      in response to Plasmodium indicates that homologs of effector (NOS) and regulator
      (TGF-beta1) gene super families may defend evolutionarily diverse hosts against a
      shared pathogen.

PMID- 12798029
TI  - Evolutionary rate differences in trypanosomes.
AB  - Ribosomal RNA-based studies of trypanosome phylogenies have highlighted
      considerable differences in genetic diversity within clades in the genus
      Trypanosoma and several-fold substitution rate differences between clades have
      been identified. While early 18S rRNA-based studies were hampered by highly
      variable substitution rates and long-branch attraction, it is apparent that
      genuine differences in evolution rates within localized clades do exist and
      questions remain regarding what rate or rates such clades are evolving at and why
      is the application of a single clock to trypanosome evolution so inappropriate?
      In this study, we explore rate heterogeneity in the commonly used 18S rRNA gene
      across genus Trypanosoma, using a maximum likelihood (ML) approach to explore
      local rate variations in clades of biological interest.

PMID- 12798030
TI  - Evolutionary history conditions the timing of transmission in vesicular
      stomatitis virus.
AB  - It has been postulated that early transmitted viruses would evolve to be more
      virulent than late transmitted ones. The reason for this prediction is that early
      transmission selects for rapid viral replication and, consequently, rapid host
      death, whereas late transmission would select for slow-replicating viruses that
      permit longer survival to the host. To test this prediction, experimental
      lineages of vesicular stomatitis virus (VSV) had been adapted to three different
      transmission dynamics during more than 100 generations. Transmission dynamic
      differed in the stage of infection at which transmission took place: early,
      intermediate or late. Regardless the timing of transmission imposed during the
      competition experiments done for estimating fitness, lineages adapted to an
      intermediate time of transmission reached higher fitness than viruses adapted to
      either early or late transmission. Viruses adapted to early and late transmission
      schedules showed a trade-off in their performance at other transmission times,
      with higher fitness at their own transmission time than at any other. The basis
      of fitness differences, in terms of growth parameters, have also been explored.
      Fitness correlated with the rate of growth and with the moment of maximum
      population density but not with the maximum density itself. In addition, a
      positive correlation between virus performance at late transmission and stability
      outside the cellular host has been detected.

PMID- 12798031
TI  - Population genetics and population biology: what did they bring to the
      epidemiology of transmissible diseases? An e-debate.

PMID- 12798032
TI  - MEEGID-V: Fifth International Meeting on Molecular Epidemiology and Evolutionary
      Genetics in Infectious Diseases.

PMID- 12798034
TI  - Isochores merit the prefix 'iso'.
AB  - The isochore concept in the human genome sequence was challenged in an analysis
      by the International Human Genome Sequencing Consortium (IHGSC). We argue here
      that a statement in the IHGSC's analysis concerning the existence of isochores is
      misleading, because the homogeneity was not examined at a large enough length
      scale and consequently an inappropriate statistical test was applied. A test of
      the existence of isochores should be equivalent to a test of homogeneity or
      equality of windowed GC%. The statistical test applied in the IHGSC's analysis,
      the binomial test, is a test of whether individual bases are independent and
      identically-distributed (iid). For testing the existence of isochores, or
      homogeneity in windowed GC%, we propose to use another statistical test: the
      analysis of variance (ANOVA). It can be shown that DNA sequences that are
      rejected by the binomial test may not be rejected by the ANOVA test.

PMID- 12798035
TI  - A knot or not a knot? SETting the record 'straight' on proteins.
AB  - A novel knot found in the SET domain is examined in the light of five recent
      crystal structures and their descriptions in the literature. Using the algorithm
      of Taylor it was established that the backbone chain does not form a true knot.
      However, only two crosslinks corresponding to hydrogen-bonds were needed to form
      a knotted structure. Such loosely knotted structures formed by hydrogen-bonded
      crosslinks were assessed as lying between covalent crosslinks (such as disulphide
      bonds) and threaded-loops which are formed by close (unbonded) contacts between
      different parts of the chain. The term pseudo-knot was introduced (from the RNA
      field) to distinguish hydrogen-bonded 'knots'.

PMID- 12798037
TI  - Consistency checks for characterizing protein forms.
AB  - Proteomics enforces the reverse chronological order on the gene to protein dogma
      and imposes amino acid sequences as a starting point of an investigation relative
      to function. By this approach, proteomics data can confirm the presence of
      multiple forms of a protein. Notwithstanding variations attributed specific
      individual features of organisms and tissues, from two to over ten protein forms
      can be identified in a given sample. The present work describes some guidelines
      for tracking the origin of alternative protein forms and attempts to tag the
      details of sequence data in the literature. Working via these guidelines we have
      uncovered a third alternative form of the Pim subfamily of oncogenes. The term
      form is here combined with the qualification alternative to describe any product
      of a given gene including closely related paralogs. This paper also emphasizes
      the need for consistency checks in annotation processes, such as gene clustering,
      to avoid losing important details describing protein alternative forms. By
      identifying alternative protein forms, we illustrate the fact that rationalizing
      of protein function via the identification of protein-protein interactions should
      in reality be that of identifying (alternative) form-form interactions.

PMID- 12798038
TI  - Protein family classification and functional annotation.
AB  - With the accelerated accumulation of genomic sequence data, there is a pressing
      need to develop computational methods and advanced bioinformatics infrastructure
      for reliable and large-scale protein annotation and biological knowledge
      discovery. The Protein Information Resource (PIR) provides an integrated public
      resource of protein informatics to support genomic and proteomic research. PIR
      produces the Protein Sequence Database of functionally annotated protein
      sequences. The annotation problems are addressed by a classification-driven and
      rule-based method with evidence attribution, coupled with an integrated knowledge
      base system being developed. The approach allows sensitive identification,
      consistent and rich annotation, and systematic detection of annotation errors, as
      well as distinction of experimentally verified and computationally predicted
      features. The knowledge base consists of two new databases, sequence analysis
      tools, and graphical interfaces. PIR-NREF, a non-redundant reference database,
      provides a timely and comprehensive collection of all protein sequences, totaling
      more than 1,000,000 entries. iProClass, an integrated database of protein family,
      function, and structure information, provides extensive value-added features for
      about 830,000 proteins with rich links to over 50 molecular databases. This paper
      describes our approach to protein functional annotation with case studies and
      examines common identification errors. It also illustrates that data integration
      in PIR supports exploration of protein relationships and may reveal protein
      functional associations beyond sequence homology.

PMID- 12798039
TI  - Automated annotation of microbial proteomes in SWISS-PROT.
AB  - Large-scale sequencing of prokaryotic genomes demands the automation of certain
      annotation tasks currently manually performed in the production of the SWISS-PROT
      protein knowledgebase. The HAMAP project, or 'High-quality Automated and Manual
      Annotation of microbial Proteomes', aims to integrate manual and automatic
      annotation methods in order to enhance the speed of the curation process while
      preserving the quality of the database annotation. Automatic annotation is only
      applied to entries that belong to manually defined orthologous families and to
      entries with no identifiable similarities (ORFans). Many checks are enforced in
      order to prevent the propagation of wrong annotation and to spot problematic
      cases, which are channelled to manual curation. The results of this annotation
      are integrated in SWISS-PROT, and a website is provided at
      http://www.expasy.org/sprot/hamap/.

PMID- 12798040
TI  - Gene teams: a new formalization of gene clusters for comparative genomics.
AB  - This paper describes an efficient algorithm based on a new concept called gene
      team for detecting conserved gene clusters among an arbitrary number of
      chromosomes. Within the clusters, neither the order of the genes nor their
      orientation need be conserved. In addition, insertion of foreign genes within the
      clusters are permitted to a user-defined extent. This algorithm has been
      implemented in a publicly available TEAM software that proves to be an efficient
      tool for systematic searches of conserved gene clusters. Examples of actual
      biological results are provided. The software is downloadable from http://www
      igm.univ-mlv.fr/ approximately raffinot/geneteam.html.

PMID- 12798041
TI  - A HMM-based method to predict the transmembrane regions of beta-barrel membrane
      proteins.
AB  - A novel method is developed to model and predict the transmembrane regions of
      beta-barrel membrane proteins. It is based on a Hidden Markov model (HMM) with
      architecture obeying those proteins' construction principles. The HMM is trained
      and tested on a non-redundant set of 11 beta-barrel membrane proteins known to
      date at atomic resolution with a jack-knife procedure. As a result, the method
      correctly locates 97% of 172 transmembrane beta-strands. Out of the 11 proteins,
      the barrel size for ten proteins and the overall topology for seven proteins are
      correctly predicted. Additionally, it successfully assigns the entire topology
      for two new beta-barrel membrane proteins that have no significant sequence
      homology to the 11 proteins. Predicted topology for two candidates for beta
      barrel structure of the outer mitochondrial membrane is also presented in the
      paper.

PMID- 12798044
TI  - The golden age of genetics and the dark age of infectious diseases.

PMID- 12798042
TI  - Hidden Markov models and optimized sequence alignments.
AB  - We present a formulation of the Needleman-Wunsch type algorithm for sequence
      alignment in which the mutation matrix is allowed to vary under the control of a
      hidden Markov process. The fully trainable model is applied to two problems in
      bioinformatics: the recognition of related gene/protein names and the alignment
      and scoring of homologous proteins.

PMID- 12798045
TI  - Do human and JC virus genes show evidence of host-parasite codemography?
AB  - Information about similarities and differences in the demographic history of host
      and parasite populations is potentially useful for making inferences about a
      variety of evolutionary processes. However, it is difficult to observe the
      historical demographic properties of natural populations directly. Here, the
      extent of demographic similarity in a host and its parasite was examined
      indirectly by inferring long-term population history from patterns of genetic
      variation. Nucleotide sequence diversity in human and JC virus (JCV) DNA is
      consistent with a long-term demographic connection between the two species: both
      show evidence of large-scale population expansion. However, genetic data also
      suggest that the two species have different patterns of population
      substructuring. These similarities and differences have implications for adaptive
      evolution in JCV that are not evident when the two species are considered
      separately.

PMID- 12798046
TI  - Evolution of the Old World Arenaviridae and their rodent hosts: generalized host
      transfer or association by descent?
AB  - Ten scenarios optimizing the number of cospeciation events between the
      phylogenies of the Old World Arenaviridae (OWA) and their murine hosts are tested
      while attempting to answer the following questions. Does the coevolutionary model
      explain their respective distribution? What kind of evolutionary events could
      have most frequently contributed to the horizontal and/or vertical transmission
      of the OWA? How to define secondary hosts and to interpret their existence in the
      evolutionary process? Where are the geographical origins of the OWA? All
      scenarios support the "diffuse coevolution" hypothesis previously proposed for
      the OWA, in which parallel phylogeny and/or host switches on closely related
      hosts can be considered as the most common mechanisms of transmission. The
      scenarios allow defining more precisely the concepts of principal and secondary
      hosts. Such scenarios also suggest that the diversity of the viruses and their
      rodent hosts could be higher than currently expected and that cophylogeny could
      have been underestimated. The "diffuse coevolution" hypothesis permits to
      interpret the transfer of the viruses to distant hosts as a result of a
      disturbance in their regular mode of dispersion, which could match with the
      periods of emergence as human parasites. The comparison of the viral phylogeny
      with the host cladogram also suggests that the viruses parasitized the Murinae
      before several lineages became distinct and spread in Africa. This supposes that
      the origin of the arenaviruses has to be found out of Africa.

PMID- 12798047
TI  - Isoenzyme variability of five principal triatomine vector species of Chagas
      disease in Mexico.
AB  - Triatoma barberi, T. dimidiata, T. longipennis, T. pallidipennis and T.
      picturata, all key Chagas disease vectors in Mexico, were analysed by multilocus
      enzyme electrophoresis (MLEE) at 17 putative loci. The majority of insect
      specimens studied were collected from domestic and peridomestic structures from
      multiple geographic locations while others were collected from sylvatic areas. T.
      barberi was the least polymorphic species (P(0.95)=0.18), with polymorphism rates
      of the other species ranging from 0.29 to 0.50. T. barberi, a member of the
      protracta complex, clustered apart from the other studied species by Nei's
      genetic distance with >1.36, and at least eight loci were found to be diagnostic
      for this species. T. dimidiata was more related to T. longipennis, T.
      pallidipennis and T. picturata (phyllosoma complex) than to T. barberi, with a
      genetic distance averaging 0.36 with the phyllosoma complex species. In contrast,
      the genetic distances between the three phyllosoma complex species were not
      significantly different from zero, and there were no species-specific loci
      differentiating among them. The results strongly support the grouping of these
      three species in one complex, separate from the two other species studied.

PMID- 12798048
TI  - Dynamics of bacterial colonisation in the respiratory tract of patients with
      cystic fibrosis.
AB  - Mutations in the human genome may result in altered phenotypes. The cystic
      fibrosis (CF) patient, for instance, suffers from an aberrant composition of the
      epithelial lining of the gastrointestinal and respiratory tract. In this
      particular case, a single point mutation in the cystic fibrosis conductance
      regulator (CFTR) gene results in major physiological changes resulting in
      ecological changes that generate a niche particularly attractive to a selected
      set of microbial pathogens. We here present a review on the dynamics of the
      bacterial populations inhabiting the CF lung. Studies focusing on Staphylococcus
      aureus, Haemophilus influenzae and Pseudomonas aeruginosa will be summarised and
      discussed, whereas the technology used for microbial characterisation will be
      shortly highlighted. Emphasis, however, will be on those studies that assessed
      the genetic diversity among clinical isolates that were obtained over prolonged
      periods of time, enabling the distinction between persistent colonisation versus
      frequent re-infection by the selected pathogens. Evolutionary adaptation of
      pathogens to the CF lung is a common theme in many of these studies.

PMID- 12798049
TI  - Transmission bottlenecks and the evolution of fitness in rapidly evolving RNA
      viruses.
AB  - We explored the evolutionary importance of two factors in the adaptation of RNA
      viruses to their cellular hosts, size of viral inoculum used to initiate a new
      infection, and mode of transmission (horizontal versus vertical). Transmission
      bottlenecks should occur in natural populations of viruses and their profound
      effects on viral adaptation have been previously documented. However, the role of
      transmission mode has not received the same attention. Here we used a factorial
      experimental design to test the combined effects of inoculum (bottleneck) size
      and mode of transmission in evolution of vesicular stomatitis virus (VSV) in
      tissue culture, and compared our results to the predictions of a recent
      theoretical model. Our data were in accord with basic genetic principles
      concerning the balance between mutation, selection and genetic drift. In
      particular, attenuation of vertically transmitted viruses was a consequence of
      the random accumulation of deleterious mutations, whereas horizontally
      transmitted viruses experiencing similar bottlenecks did not suffer the same
      fitness losses because effective bottleneck size was actually determined by the
      number of host individuals. In addition, high levels of viral fitness in
      horizontally transmitted populations were explained by competition among viral
      variants.

PMID- 12798050
TI  - Genomic polymorphism of Leishmania infantum: a relationship with clinical
      pleomorphism?
AB  - Leishmania infantum is the etiological agent of visceral (VL) and a cutaneous
      form (CL) of leishmaniasis around the Mediterranean Basin. In order to document
      the parasite genetic background corresponding to this clinical diversity,
      chromosome size polymorphism was analysed in 32 French isolates (18 CL and 14 VL)
      originating from the Cevennes and the Pyrenees Orientales (PO), and corresponding
      to zymodemes MON-1 and MON-29. Five chromosomes bearing tandemly repeated genes
      encoding for important antigens (gp63, PSA-2 and K39) or key metabolic functions
      (mini-exon and rDNA) were studied. Significant size variation (100-270 kbp) was
      observed for chromosomes bearing mini-exon, PSA-2 and rDNA genes, which involved
      variation in copy number of corresponding genes. The two other chromosomes showed
      smaller size-variation and did not involve dosage of gp63 and K39 genes.
      Chromosomal size showed correlation with geography and clinical origin: (i)
      chromosome 2 (mini-exon) was found to be significantly smaller in the PO; (ii)
      chromosomes 12 (PSA-2) and 27 (rDNA) were significantly smaller in the strictly
      cutaneous MON-29 isolates. Gene rearrangements and their synergistic effects on
      the phenotypic expression of the parasite are discussed.

PMID- 12798051
TI  - The origin and evolution of the Leishmania donovani complex as inferred from a
      mitochondrial cytochrome oxidase II gene sequence.
AB  - Members of the Leishmania donovani complex are parasites of the reticulo
      endothelial system that are often associated with serious epidemics of a life
      threatening disease known as visceral leishmaniasis or kala-azar. Twenty-two
      Leishmania isolates representative of the geographical range of the parasite were
      analysed for sequence variations in their cytochrome oxidase II gene. In
      performing phylogenetic analysis, the maximum parsimonious, neighbour joining and
      maximum likelihood trees were congruent and produced a tree that differentiated
      between two clades conforming to the current classification of the species
      complex into two species: Leishmania donovani and Leishmania infantum.
      Furthermore, the molecular haplotypes were concordant, in general, with the
      isoenzyme data of the complex. The donovani isolates from the Sudan that
      possessed the most ancestral sequence were of a single haplotype that
      significantly resembled the sequence of Leishmania major. Our sequence data
      tallied with a general neutral model of sequence evolution with manifestations of
      weak selection. The data allowed an approximate dating of the origin of the
      complex to a period contemporary to or predating the spread of modern humans out
      of Africa.

PMID- 12798052
TI  - Infectious diseases and the golden age of phylogenetics: an E-debate.

PMID- 12798054
TI  - Acceleration of cartilage repair by genetically modified chondrocytes over
      expressing bone morphogenetic protein-7.
AB  - BACKGROUND: Cartilage has a limited capacity to heal. Although chondrocyte
      transplantation is a useful therapeutic strategy, the repair process can be
      lengthy. Previously we have shown that over expression of bone morphogenetic
      protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to
      increased matrix synthesis and cartilage-like tissue formation in vitro. In this
      context we hypothesized that implantation of genetically modified chondrocytes
      expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in
      an equine model of cartilage defect repair. METHODS: Chondrocytes treated with
      adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector
      encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were
      implanted into extensive (15 mm diameter) articular cartilage defects in the
      patellofemoral joints of 10 horses. Biopsies were performed to evaluate early
      healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed
      for morphology, MRI appearance, compressive strength, biochemical composition and
      persistence of implanted cells. RESULTS: Four weeks after surgery AdBMP-7-treated
      repairs showed an increased level of BMP-7 expression and accelerated healing,
      with markedly more hyaline-like morphology than control. Quantitative real-time
      polymerase chain reaction (PCR) analysis of the repair tissue 8 months after
      surgery showed that few implanted cells persisted. By this time, the controls had
      healed similarly to the AdBMP-7-treated defects, and no difference was detected
      in the morphologic, biochemical or biomechanical properties of the repair tissues
      from the two treatment groups. CONCLUSIONS: Implantation of genetically modified
      chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair
      tissue in experimental cartilage defects. CLINICAL RELEVANCE: Rehabilitation
      after cell-based cartilage repair can be prolonged, leading to decreased patient
      productivity and quality of life. This study shows the feasibility of using
      genetically modified chondrocytes to accelerate cartilage healing.

PMID- 12798055
TI  - Adhesion of perichondrial cells to a polylactic acid scaffold.
AB  - The number of chondrogenic cells available locally is an important factor in the
      repair process for cartilage defects. Previous studies demonstrated that the
      number of transplanted rabbit perichondrial cells (PC) remaining in a cartilage
      defect in vivo, after being carried into the site in a polylactic acid (PLA)
      scaffold, declined markedly within two days. This study examined the ability of
      in vitro culture of PC/PLA constructs to enhance subsequent biomechanical
      stability of the cells and the matrix content in an in vitro screening assay.
      PC/PLA constructs were analyzed after 1 h, 1 and 2 weeks of culture. The
      biomechanical adherence of PC to the PLA scaffold was tested by subjecting the
      PC/PLA constructs to a range of flow velocities (0.25-25 mm/s), spanning the
      range estimated to occur under conditions of construct insertion in vivo. The
      adhesion of PC to the PLA carrier was increased significantly by 1 and 2 weeks of
      incubation, with 25 mm/s flow causing a 57% detachment of cells after 1 h of
      seeding, but only 7% and 16% after 1 and 2 weeks of culture, respectively
      (p<0.001). This adherence was associated with marked deposition of
      glycosaminoglycan and collagen. These findings suggest that pre-incubation of PC
      laden PLA scaffolds markedly enhances the stability of the indwelling cells.

PMID- 12798056
TI  - Long-term intermittent shear deformation improves the quality of cartilaginous
      tissue formed in vitro.
AB  - The formation of cartilaginous tissue in vitro is a promising alternative to
      repair damaged articular cartilage. However, recent attempts to tissue-engineer
      articular cartilage that has similar properties to the native tissue have proven
      to be difficult. The in vitro-formed cartilaginous tissue typically has a similar
      proteoglycan content to native cartilage, but has a reduced collagen content and
      only a fraction of the mechanical properties. In this study, we investigated
      whether the intermittent application of cyclic shearing forces during tissue
      formation would improve the tissue quality. Chondrocyte cultures were stimulated
      at a 2% shear strain amplitude at a frequency of 1 Hz for 400 cycles every 2nd
      day. At one week, both collagen and proteoglycan synthesis increased (23+/-6% and
      20+/-6%, respectively) over the unstimulated, static controls. At four weeks, an
      increased amount of tissue formed (stimulated: 1.85+/-0.08, unstimulated: 1.58+/
      0.07 mg dry wt.). This tissue contained approximately 40% more collagen
      (stimulated: 511+/-23, unstimulated: 367+/-24 microg/construct) and 35% more
      proteoglycans (stimulated: 376+/-21, unstimulated: 279+/-26 microg/construct).
      Tissues that formed in the presence of shearing forces also displayed a 3-fold
      increase in compressive load-bearing capacity (stimulated: 16+/-5, unstimulated:
      5+/-1 kPa max. equilibrium stress) and a 6-fold increase in stiffness
      (stimulated: 112+/-36, unstimulated: 20+/-6 kPa max. equilibrium modulus)
      compared to the static controls. These results demonstrate that intermittent
      application of dynamic shearing forces over a four-week period improves the
      quality of cartilaginous tissue formed in vitro. Interestingly, low amplitudes of
      shear stimulation for short periods of time (6 min of stimulation applied every
      2nd day) produced these changes.

PMID- 12798057
TI  - Effect of dynamic hydrostatic pressure on rabbit intervertebral disc cells.
AB  - The pathogenesis of vibration-induced disorders of intervertebral disc at the
      cellular level is largely unknown. The objective of this study was to establish a
      method to investigate the ranges of constructive and destructive hydrostatic
      loading frequencies and amplitudes in preventing or inducing extracellular disc
      matrix degradation. Using a hydraulic chamber, normal rabbit intervertebral disc
      cells were tested under dynamic hydrostatic loading. Monolayer cultures of disc
      outer annulus cells and 3-dimensional (3-D) alginate cultures of disc nucleus
      pulposus cells were tested. Effects of different loading amplitudes (3-D culture,
      0-3 MPa; monolayer, 0-1.7 MPa) and frequencies (1-20 Hz) on disc collagen and
      protein metabolism were investigated by measuring 3H-proline-labeled proteins
      associated with the cells in the extracellular matrix and release of 3H-proline
      labeled molecules into culture medium. High frequency and high amplitude
      hydrostatic stress stimulated collagen synthesis in cultures of outer annulus
      cells whereas the lower amplitude and frequency hydrostatic stress had little
      effect. For the same loading duration and repetition, neither treatment
      significantly affected the relative amount of protein released from the cell
      layers, indicating that protein degradation and stability were unaffected. In the
      3-D nucleus culture, higher amplitude and frequency increased synthesis rate and
      lowered degradation. In this case, loading amplitude had a stronger influence on
      cell response than that of loading frequency. Considering the ranges of loading
      amplitude and frequency used in this study, short-term application of high
      loading amplitudes and frequencies was beneficial in stimulation of protein
      synthesis and reduction of protein degradation.

PMID- 12798058
TI  - Adenovirus-mediated gene transfer to healing tendon--enhanced efficiency using a
      gelatin sponge.
AB  - Adenovirus-mediated gene transfer is a potential method for enhancing tendon
      healing. We investigated the transfection of Ad5CMVntLacZ, an adenovirus
      containing the reporter gene LacZ, in primary cultured human rotator cuff tendon
      cells and in a rat Achilles tendon healing model in vivo. Ad5CMVempty, the
      adenoviral vector containing no inserted gene, was used as a control for
      adenoviral transfection alone. Activity of beta-galactosidase,the protein
      expressed by LacZ gene, was measured using a beta-galactosidase assay and
      detected visually by X-gal staining. Cultured cells were successfully transfected
      without impairing cell viability. Maximal beta-galactosidase activity was
      detected when cells were transfected at the dose of 1000 PFU/cell. The duration
      of LacZ expression was six days with a peak value at 24 h post-transfection. A
      transfection rate of 100% was obtained at 5000 PFU/cell. Successful in vivo
      transfection by Ad5CMVntLacZ was obtained in healing rat Achilles tendon as
      confirmed by X-gal staining. 0.4% of tendon cells were transfected when
      Ad5CMVntLacZ was injected into the tendon at a dose of 10(6) PFU. The rate rose
      to 2% with 10(8) PFU and 3% with 10(9) PFU. The duration of LacZ expression in
      vivo was 17 days. Transfection efficiency was enhanced threefold and localization
      improved when a gelatin sponge was used to deliver the adenovirus. The results
      demonstrate that adenovirus can be used to deliver a gene of interest to cultured
      human rotator cuff tendon cells and healing tendon, with gelatin sponge
      implantation enhancing adenoviral transfection efficiency in vivo.

PMID- 12798059
TI  - Mechanical factors influence the expression of endostatin--an inhibitor of
      angiogenesis--in tendons.
AB  - Avascular zones of tendons are predisposed for degenerative changes and
      spontaneous rupture. Therefore, we analyzed the expression of the endogenous
      angiogenesis inhibiting factor endostatin in human fetal and adult tendons by
      immunohistochemical and biochemical methods. Moreover, to elucidate factors
      involved in the regulation of vascularity, we exposed primary cultures of rat
      tendon cells to intermittent hydrostatic pressure (0.2 MPa, 0.1 Hz for 24 h), and
      measured the endostatin content by ELISA and the effect of the conditioned medium
      to the proliferation of human umbilical vein endothelial cells (HUVEC). In fetal
      tendons high endostatin levels could be quantified by ELISA whereas low levels
      were found in adult tissue. In fetal tendons endostatin could also be
      immunostained in endothelial cells but mainly in fibroblasts. In adult Achilles
      tendons endostatin immunostaining was restricted to endothelial cells. In the
      tibialis posterior tendon--as an example for "wrap around"--endostatin
      immunostaining remained positive in the fibrocartilage adjacent to the medial
      malleolus. Fibrochondrocytes of the type II collagen positive fibrocartilage were
      intensively stained with the endostatin antibody. Factor VIII immunostaining
      showed that this region was largely avascular. Monolayer cultures of tendon cells
      released measurable amounts of endostatin into their culture supernatants.
      Application of intermittent hydrostatic pressure increased endostatin expression
      significantly. The conditioned media of tendon fibroblasts cultivated under
      intermittent hydrostatic pressure inhibited the proliferation of HUVEC in a dose
      dependent way. The spatial expression of endostatin in adult gliding tendons
      suggests that mechanical factors are involved in the regulation of this anti
      angiogenic factor. In accordance, tendon cells exposed to intermittent
      hydrostatic pressure inhibit endothelial cell proliferation via humoral factors
      and produce endostatin. These findings support the view that the development and
      maintenance of avascular zones in tendons might be caused by a mechanically
      induced upregulation of anti-angiogenic factors.

PMID- 12798060
TI  - A comparative dose-response study of cartilage-derived morphogenetic protein
      (CDMP)-1, -2 and -3 for tendon healing in rats.
AB  - Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone
      morphogenetic protein (BMP) family, are known to be cartilage and bone inducers
      as well as to induce tendon and ligament-like tissue. In this study we
      investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2
      and 10 microg) on tendon healing in a rat model, as well as differences in
      osteogenesis between the different CDMPs and doses.In 110 rats, a 3 mm segment of
      the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was
      injected into the defect 6 h postoperative. The rats were killed 8 days after
      operation. The tendon regenerates were tested biomechanically. There was a
      significant dose-related increase in strength and stiffness with all three CDMPs,
      but no difference between the CDMPs was found. Another 50 rats were used to
      compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP
      1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in
      all groups, including the controls. Some specimens in all groups contained bone,
      except the controls. No difference between the CDMPs could be demonstrated. The
      CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than
      controls. Only the CDMP-2 group and the controls contained significantly less
      calcium than the OP-1 group.In conclusion, the three CDMPs appeared similar as
      regards improvement of tendon repair and osteogenicity in this setting.

PMID- 12798062
TI  - Bone formation following transplantation of genetically modified primary bone
      marrow stromal cells.
AB  - Bone marrow stromal cells contain mesenchymal stem cells that can differentiate
      into a variety of mesenchymal tissues; in the presence of BMP-2, for example,
      they differentiate into osteoblasts. We constructed replication-deficient
      adenoviral vectors encoding human BMP-2 (BMP-2/Ad) or BMP-4 (BMP-4/Ad) and used
      them to transduce primary bone marrow stromal cells from the femurs of four-week
      old female C3H mice, which then expressed and processed functional BMP-2 or BMP-4
      protein. Enzyme assays and histochemical staining showed both groups of cells to
      possess alkaline phosphatase activity, a marker of differentiation into
      osteoblasts, though the activity was higher in cells transduced with BMP-2/Ad.
      When BMP-2/Ad-transduced cells were injected into the thigh muscles of
      immunocompetent C3H mice, ossicle development was detected on radiographs within
      four weeks after injection. Moreover, histological analysis indicated that newly
      developed ossicles contain mature osseous components, including cortical bone and
      bone marrow, within eight weeks. Thus, syngeneic transplantation of genetically
      modified primary bone marrow stromal cells induced bone formation in
      immunocompetent mice, perhaps indicating its potential for use in the development
      of therapeutic protocols aimed at enhancing bone formation.

PMID- 12798061
TI  - Bone induction by BMP-2 transduced stem cells derived from human fat.
AB  - PURPOSE: We have isolated pluripotent mesenchymal progenitor cells in large
      numbers from liposuction aspirates (processed lipoaspirate cells or PLAs). This
      study examines the osteogenic potential of PLAs and bone marrow aspirate cells
      (BMAs), when exposed to either recombinant human bone morphogenetic protein (BMP)
      2 (rh-BMP-2) or adenovirus containing BMP-2 cDNA (Ad-BMP-2). METHODS: Liposuction
      aspirates underwent proteolytic digestion to obtain PLAs. After exposure to
      exogenous rh-BMP-2 or Ad-BMP-2 for four or seven days, PLAs and BMAs were
      assessed by histochemistry, spectrophotometry and RT-PCR. Western blotting and
      ELISA confirmed BMP gene transduction. Results were compared to osteoblasts and
      cells in osteogenic media only. PLA-Ad-BMP-2 cells were seeded on matrices and
      implanted in the hind limbs of SCID mice. RESULTS: Analysis of quantified bone
      precursor assays including extracellular ALP histomorphometry, intracellular ALP
      spectrophotometry, and calcified extracellular matrix (von Kossa)
      histomorphometry revealed that PLAs treated with exogenous rh-BMP-2 or transduced
      with a BMP-2 containing adenovirus (PLA-Ad-BMP-2) produced more bone precursors
      than osteoblasts (p=0.001). PLAs treated with exogenous rh-BMP-2 or PLA-Ad-BMP-2
      also produced more bone precursors than BMAs (p=0.001), except for day 7 ALP
      histomorphometry (p=0.343). ELISA confirmed successful BMP-2 production by both
      progenitor cell groups transduced with Ad-BMP-2. H&E sections from collagen I
      matrices seeded with PLA-Ad-BMP-2 cells confirmed bone formation at six weeks.
      CONCLUSIONS: Liposuction aspirates contain PLAs that can be transfected with the
      BMP-2 gene, with rapid induction into the osteoblast phenotype at a rate
      comparable to rh-BMP-2 and osteoblast groups. Transduced PLAs produce more bone
      precursors with faster onset of calcified extracellular matrix than transduced
      BMAs. PLAs may be an ideal source of mesenchyme-lineage stem cells for gene
      therapy and tissue engineering.

PMID- 12798063
TI  - Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast
      like cells.
AB  - Implant surface morphology regulates osteoblast phenotypic expression. Osteoblast
      sensitivity to non-biologic surfaces suggests that native bone surface features
      may also affect osteoblast response. To test this, MG63 osteoblast-like cells
      were grown for 7 days on bovine cortical bone wafers pretreated with rat bone
      marrow osteoclasts for 0, 10 or 20 days. Response to osteoclast-treated surfaces
      was compared to the response of MG63 cells to titanium surfaces with smooth and
      rough microtopographies. Cell number, differentiation (alkaline phosphatase
      activity and osteocalcin levels), and local factors (PGE(2) and TGF-beta1) were
      measured in confluent cultures. Compared to culture on plastic, cell number was
      reduced on all three types of bone wafers; this effect was dose-dependent with
      increasing resorption of the surface. Alkaline phosphatase specific activity was
      increased (P<or=0.05) on all three surfaces compared with plastic, but this
      increase was not dependent on resorption time, indicating this parameter was
      sensitive to the surface (bovine bone vs. plastic) but not to osteoclast
      resorption. There was a direct correlation between the area of the bone surface
      resorbed and the amount of osteocalcin, TGF-beta1 and PGE(2) (R(2)=0.8025,
      0.8689, 0.8896, respectively). With 20 days of osteoclast pretreatment, there was
      a 20-fold increase in osteocalcin over plastic and a 7-fold increase over
      cultures on untreated bone wafers. Similar increases were found for TGF-beta1 and
      PGE(2). Thus, surface changes resulting from osteoclast pretreatment have a
      strong effect on osteoblast phenotypic expression, and suggest that
      microtopography may play a role.

PMID- 12798064
TI  - Quantitative and sensitive in vitro assay for osteoinductive activity of
      demineralized bone matrix.
AB  - A sensitive, rapid, reliable and quantitative method to check the bone forming
      potential of demineralized bone matrix (DBM) has been developed. The
      osteoinductivity of the bone morphogenetic proteins (BMPs), present in DBM, can
      be measured in vitro using a pluripotent myoblast C2C12 cell line. Alkaline
      phosphatase activity induced by co-incubation of DBM with C2C12 cells was dose
      responsive and corresponds to the amount of active BMPs in DBM. Bone forming
      potential was simultaneously tested in vivo by implanting DBM intra-muscularly in
      nude rats. ALP activity induced in C2C12 cells, correlated with bone formation in
      vivo (r=0.88), determined by alkaline phosphatase activity, mineralization
      density and histomorphology of the DBM explants. Results from DBM batches,
      originating from five established Bone Banks, showed good consistency between in
      vitro and in vivo assays. However, DBM activity varied widely from bank to bank
      as well as from batch to batch within the same bank.

PMID- 12798065
TI  - A resorbable porous ceramic composite bone graft substitute in a rabbit
      metaphyseal defect model.
AB  - The success of converted corals as a bone graft substitute relies on a complex
      sequence of events of vascular ingrowth, differentiation of osteoprogenitor
      cells, bone remodeling and graft resorption occurring together with host bone
      ingrowth into and onto the porous coralline microstructure or voids left behind
      during resorption. This study examined the resorption rates and bone infiltration
      into a family of resorbable porous ceramic placed bilaterally in critical sized
      defects in the tibial metaphyseal-diaphyseal of rabbits. The ceramics are made
      resorbable by partially converting the calcium carbonate of corals to form a
      hydroxyapatite (HA) layer on all surfaces. Attempts have been made to control the
      resorption rate of the implant by varying the HA thickness. New bone was observed
      at the periosteal and endosteal cortices, which flowed into the centre of the
      defect supporting the osteoconductive nature of partially converted corals. The
      combination of an HA layer and calcium carbonate core provides a composite bone
      graft substitute for new tissue integration. The HA-calcium carbonate composite
      demonstrated an initial resorption of the inner calcium carbonate phase but the
      overall implant resorption and bone ingrowth behaviour did not differ with HA
      thickness.

PMID- 12798066
TI  - The initial phase of fracture healing is specifically sensitive to mechanical
      conditions.
AB  - Interfragmentary movements affect the quality and quantity of callus formation.
      The mounting plane of monolateral external fixators may give direction to those
      movements. Therefore, the aim of this study was to determine the influence of the
      fixator mounting plane on the process of fracture healing. Identically configured
      fixators were mounted either medially or anteromedially on the tibiae of sheep.
      Interfragmentary movements and ground reaction forces were evaluated in vivo
      during a nine week period. Histomorphological and biomechanical parameters
      described the bone healing processes. Changing only the mounting plane led to a
      modification of interfragmentary movements in the initial healing phase. The
      difference in interfragmentary movements between the groups was only significant
      during the first post-operative period. However, these initial differences in
      mechanical conditions influenced callus tissue formation significantly. The group
      with the anteromedially mounted fixator, initially showing significantly more
      interfragmentary movements, ended up with a significantly smaller callus diameter
      and a significantly higher callus stiffness as a result of advanced fracture
      healing. This demonstrates that the initial phase of healing is sensitive to
      mechanical conditions and influences the course of healing. Therefore, initial
      mechanical stability of an osteosynthesis should be considered an important
      factor in clinical fracture treatment.

PMID- 12798067
TI  - Differential inhibition of fracture healing by non-selective and cyclooxygenase-2
      selective non-steroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) specifically inhibit
      cyclooxygenase (COX) activity and are widely used as anti-arthritics, post
      surgical analgesics, and for the relief of acute musculoskeletal pain. Recent
      studies suggest that non-specific NSAIDs, which inhibit both COX-1 and COX-2
      isoforms, delay bone healing. The objectives of this study were 2-fold; first, to
      measure the relative changes in the normal expression of COX-1 and COX-2 mRNAs
      over a 42 day period of fracture healing and second, to compare the effects of a
      commonly used non-specific NSAID, ketorolac, with a COX-2 specific NSAID,
      Parecoxib (a pro-drug of valdecoxib), on this process. Simple, closed, transverse
      fractures were generated in femora of male Sprague-Dawley rats weighing
      approximately 450 g each. Total RNA was prepared from the calluses obtained prior
      to fracture and at 1, 3, 5, 7, 10, 14, 21, 35 and 42 days post-fracture and
      levels of COX-1 and COX-2 mRNA were measured using real time PCR. While the
      relative levels of COX-1 mRNA remained constant over a 21-day period, COX-2 mRNA
      levels showed peak expression during the first 14 days of healing and returned to
      basal levels by day 21. Mechanical properties of the calluses were then assessed
      at 21 and 35 days post-fracture in untreated animals and animals treated with
      either ketorolac or high or low dose parecoxib. At both 21 and 35 days after
      fracture, calluses in the group treated with the ketorolac showed a significant
      reduction in mechanical strength and stiffness when compared with controls
      (p<0.05). At the 21-day time point, calluses of the parecoxib treated animals
      showed a lower mean mechanical strength than controls, but the inhibition was not
      statistically significant. Based on physical analysis of the bones, 3 of 12 (25%)
      of the ketorolac-treated and 1 of 12 (8%) of the high dose parecoxib-treated
      animals showed failure to unite their fractures by 21 days, while all fractures
      in both groups showed union by 35 days. Histological analysis at 21 days showed
      that the calluses in the ketorolac-treated group contained substantial amounts of
      residual cartilage while neither the control nor the parecoxib-treated animals
      showed comparable amounts of cartilage at this stage. These results demonstrate
      that ketorolac and parecoxib delay fracture healing in this model, but in this
      study daily administration of ketorolac, a non-selective COX inhibitor had a
      greater affect on this process. They further demonstrate that a COX-2 selective
      NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying
      fracture healing even at doses that are known to fully inhibit prostaglandin
      production.

PMID- 12798068
TI  - Effects of receptor activator of NFkappaB (RANK) signaling blockade on fracture
      healing.
AB  - As dominant regulators of osteoclastogenesis and bone resorption, receptor
      activator of NFkappaB (RANK), receptor activator of NFkappaB ligand, and OPG have
      been identified as ideal drug targets for the treatment of metabolic bone
      disease. One concern regarding the therapeutic use of RANK signaling inhibitors
      is their effect on fracture healing. Therefore we tested if uncoupling and
      osteoclast depletion via RANK blockade affects callus formation, maturation and
      matrix remodeling, as well as union rates in a mouse tibia fracture model. Low
      dose (1 mg/kg i.p.) RANK:Fc therapy had no effect on callus formation, matrix
      maturation and remodeling, and resulted in 100% bony union by day 28. High dose
      RANK:Fc treatment (10 mg/kg i.p.) effectively eliminated osteoclasts at the
      fracture site on day 14, with no significant effects on fracture healing. When
      therapy was discontinued, normal numbers of osteoclasts were observed at the
      fracture site by day 28. However, continuous therapy resulted in a large
      osteopetrotic callus consisting of both mineralized and unmineralized matrix that
      was void of osteoclasts, but bony union was unaffected at day 28. We also
      evaluated this process in the complete absence of RANK signaling using RANK -/-
      mice. These animals exhibited significant radiographic and histologic evidence of
      callus formation, indicating that RANK signaling is not required for fracture
      callus formation. However, only 33% of RANK -/- animals formed bony unions
      compared to 100% of the osteopetrotic control mice. This defect was most likely a
      result of decreased blood flow, as evidenced by fewer blood vessels in the RANK 
      /- animals. Together, these data imply that osteoclast depletion via inhibition
      of RANK signaling is a viable option for the treatment of pathological bone loss
      since no adverse effects on fracture healing are observed when therapy is
      discontinued.

PMID- 12798069
TI  - An externally fixed femoral fracture model for mice.
AB  - Transgenic and knockout mouse models can be used to help understand the molecular
      mechanisms of fracture repair. This study examines the feasibility of applying an
      external fixator to the mouse femur as one model for studying fracture repair.
      The external fixator consisted of two aluminum blocks connected by two rods. Four
      pins are used to connect the blocks to the bone. Mechanical characterization of
      the fixators was carried out prior to their use. Sixty-two wild type mice with
      bilateral femoral fractures were created using an open technique and fixed using
      the fixator. The progress of fracture healing was monitored radiologically before
      sacrifice and by mechanical testing and histology after sacrifice. Initially four
      mice died intraoperatively from excessive blood loss, the intraoperative
      mortality was subsequently reduced by subcutaneous saline infusion. The bone
      healed between 14 and 21 days after fracture and remodeled by 60 days. Both
      radiological and mechanical assessments showed a steady progression of bone
      healing. Histology demonstrated callus and endochondral bone formation. This
      study demonstrated that it is possible to create a mouse femoral fracture model
      stabilized by external fixation and will provide an additional model to the
      understanding of fracture healing in transgenic and knockout mice.

PMID- 12798070
TI  - Bone mineral density and biochemical markers of bone turnover in aseptic
      loosening after total hip arthroplasty.
AB  - The aims of this study were to determine whether subjects with aseptic loosening
      after total hip arthroplasty (THA) have regional differences in periprosthetic
      bone mineral density (BMD) and systemic biochemical markers of bone turnover
      compared to subjects with successful implants.Proximal femoral and pelvic BMD
      were measured by dual energy X-ray absorptiometry and bone turnover markers were
      assayed in 49 subjects 12.6+/-4.3 (mean+/-SD) years after cemented THA. Femoral
      BMD was lower in Gruen zones 2, 5, 6, and 7 in subjects with a loose femoral
      implant (n=17) compared to those (n=32) with fixed femoral implants (P<0.05 all
      comparisons). This BMD difference was greatest (-31%, P=0.02) in the proximal and
      medial region of the femur. Subjects with femoral loosening had higher levels of
      the bone resorption marker N-telopeptides of type-I collagen (P=0.02) than those
      with a fixed femoral implant. No differences in pelvic BMD or bone turnover
      markers were found between subjects with loose (n=18) versus fixed (n=31) pelvic
      implants. This study suggests that failure of femoral components after cemented
      THA is associated with region-specific decreases in BMD and an increase in
      urinary excretion of N-telopeptide cross-links of type-I collagen. These
      surrogate outcome markers may be of value in monitoring response to
      antiresorptive therapies used to treat periprosthetic osteolysis, although the
      diagnosis of aseptic loosening remains clinical and radiological.

PMID- 12798071
TI  - Direct and indirect induction of apoptosis in human mesenchymal stem cells in
      response to titanium particles.
AB  - The most frequent complication of total joint arthroplasty is periprosthetic
      osteolysis initiated by an inflammatory response to orthopaedic wear debris,
      which if left untreated, can result in implant instability and failure,
      eventually requiring revision surgery. We have previously reported that
      osteogenic differentiation of human marrow stroma-derived mesenchymal stem cells
      (hMSCs) is suppressed upon exposure to titanium particles, accompanied by reduced
      bone sialoprotein (BSP) gene expression, diminished production of collagen type I
      and BSP, decreased cellular viability and proliferation, and inhibition of
      extracellular matrix mineralization. In this study, we have further investigated
      hMSC cytotoxicity upon exposure to submicron particles of commercially pure
      titanium (cpTi) and zirconium oxide (ZrO(2)). Our results showed that direct
      exposure to cpTi and ZrO(2) particles compromises cell viability through the
      induction of apoptosis, eliciting increased levels of the tumor suppressor
      proteins p53 and p73, in a manner dependent on material composition, particle
      dosage, and time. Additionally, conditioned medium collected from hMSCs exposed
      to cpTi particles, but not to ZrO(2) particles, is cytotoxic to hMSCs, inducing
      apoptosis in the absence of particles. These findings demonstrate that exposure
      to orthopaedically derived wear particles can compromise hMSC viability through
      the direct and indirect induction of apoptosis. Thus, prolonged in vivo exposure
      of marrow-derived hMSCs to implant-derived wear debris is likely to reduce the
      population of viable osteoprogenitor cells, and may contribute to poor
      periprosthetic bone quality and implant loosening.

PMID- 12798072
TI  - The effect of initial graft tension on the biomechanical properties of a healing
      ACL replacement graft: a study in goats.
AB  - While a number of in vitro studies have shown that the tension on an anterior
      cruciate ligament (ACL) replacement graft at the time of fixation has an affect
      on joint stability, most in vivo studies have reported little or no long-term
      difference in outcome. The objectives of this study were to (1) establish a large
      animal model in which differences in knee stability are present at time-zero
      after ACL reconstruction with grafts fixed at a low (5 N) and high (35 N) initial
      tension and to (2) quantitatively determine if these initial effects remain after
      six weeks of healing and if the tensile properties of an ACL replacement graft
      are influenced by initial graft tension. Seventeen skeletally mature female
      Saanan breed goats were used. Using the robotic/UFS testing system, the knee
      kinematics and in situ forces in the replacement graft in response to an
      externally applied 67 N anterior-posterior (A-P) tibial load were evaluated at
      time-zero and after six weeks of healing. Afterward, the femur-ACL graft-tibia
      complexes (FGTCs) from the six-week group were tested under uniaxial tension so
      that the stress relaxation and structural properties of the FGTC were obtained.
      At time-zero, knees fixed with a high initial graft tension could better
      reproduce the A-P translation of the intact knee in response to the 67 N A-P
      tibial load. Further, in situ forces in these grafts were also closer to those in
      the intact ACL under the same external loading condition. After six weeks of
      healing, the A-P translation of the knee and in situ forces in the replacement
      grafts became similar for the low and high tension groups, while both were
      significantly different from controls. Further, the percentage of stress
      relaxation as well as the stiffness, ultimate load at failure, ultimate
      elongation at failure, and energy absorbed of the FGTCs for both reconstruction
      groups were not significantly different from each other, but were significantly
      different from controls. These results demonstrate that while the high initial
      graft tension could better replicate the normal knee kinematics at time-zero,
      these effects may diminish during the early graft healing process.

PMID- 12798073
TI  - Healing ligaments have decreased cyclic modulus compared to normal ligaments and
      immobilization further compromises healing ligament response to cyclic loading.
AB  - Ligaments help maintain joint stability by resisting excessive strain during the
      repetitive loading experienced during daily activity. Healing ligaments may be
      less able to fulfill this role, straining more under equivalent loading than
      normal ligaments. We examined the cyclic stress-strain response of normal and
      healing ligaments to repetitive low loads (<10% of the normal ligament failure
      strength). Rabbit medial collateral ligaments (MCLs) were surgically gapped in
      either a unilateral (right MCL; n=23) or bilateral (right and left MCLs; n=17)
      fashion with immobilization of the right hindlimb in the bilateral group. These
      MCL scars were allowed to heal for 3, 6, and 14 weeks and were cyclic creep
      tested at 2.2, 4.1, and 7.1 MPa, respectively. Creep test stresses were a
      constant 30% of the failure strength of non-immobilized scars at the different
      healing intervals. Normal MCLs were creep tested at 4.1 and 7.1 MPa (n=13). The
      cyclic modulus of the non-immobilized scars was less than that of normal
      ligaments. The percent increase in modulus during cycling was greater for scars
      than for normal ligaments, likely related to increased viscous dissipation or
      material inferiorities in scars. Furthermore, immobilization significantly
      decreased the ability of scars to resist strain, with a majority of immobilized
      scars failing during repetitive loading. Such failures were preceded by a
      reduction in cyclic modulus indicating damage to the healing ligaments that was
      predictive of eventual total failure. The implications of this study are that
      joints with healing ligaments may have increased strain in joint structures while
      they are under stress, potentially leading to joint instability. Although
      immobilization could be used temporarily to maintain joint stability,
      remobilization would likely lead to total failure of the healing ligament.

PMID- 12798074
TI  - The anatomy of the posterolateral aspect of the rabbit knee.
AB  - The purpose of this study was to determine the anatomy of the posterolateral
      aspect of the rabbit knee to serve as a basis for future in vitro and in vivo
      posterolateral knee biomechanical and injury studies. Twelve nonpaired fresh
      frozen New Zealand white rabbit knees were dissected to determine the anatomy of
      the posterolateral corner. The following main structures were consistently
      identified in the rabbit posterolateral knee: the gastrocnemius muscles, biceps
      femoris muscle, popliteus muscle and tendon, fibular collateral ligament,
      posterior capsule, ligament of Wrisberg, and posterior meniscotibial ligament.
      The fibular collateral ligament was within the joint capsule and attached to the
      femur at the lateral epicondyle and to the fibula at the midportion of the
      fibular head. The popliteus muscle attached to the medial edge of the posterior
      tibia and ascended proximally to give rise to the popliteus tendon, which
      inserted on the proximal aspect of the popliteal sulcus just anterior to the
      fibular collateral ligament. The biceps femoris had no attachment to the fibula
      and attached to the anterior compartment fascia of the leg. This study increased
      our understanding of these structures and their relationships to comparative
      anatomy in the human knee. This knowledge of the rabbit's posterolateral knee
      anatomy is important to understand for biomechanical and surgical studies which
      utilize the rabbit knee as a model for human posterolateral knee injuries.

PMID- 12798075
TI  - Spontaneous and experimental osteoarthritis in dog: similarities and differences
      in proteoglycan levels.
AB  - The unilateral canine model is the most commonly used model of experimental
      osteoarthritis (OA). In this model, the anterior cruciate ligament (ACL) of one
      knee is transected and the contralateral joint is usually used as a control.
      However, dogs, similar to humans, can develop OA spontaneously with old age.
      Additionally, certain breeds of dogs are genetically predisposed to OA and can
      develop symptoms at a young age. The goal of this study was to compare the
      pathological changes of proteoglycans in OA cartilage from dogs that developed OA
      spontaneously to those that underwent ACL transection. For this reason, biglycan,
      decorin and fibromodulin levels and degradation patterns were compared by Western
      blot hybridization, and aggrecan contents were quantified by dimethylmethylene
      blue assay. The changes in proteoglycan levels in the cartilage of dogs with
      spontaneous OA, regardless of their age, were very similar to those published for
      human OA cartilage. However, when OA developed as a result of ACL-surgery, the
      changes in proteoglycans were different from those of slowly developing
      spontaneous OA. Therefore, these differences should be taken into consideration
      when the ACL-transection model is used.

PMID- 12798076
TI  - Glucose-mediated in vitro glycation modulates biomechanical integrity of the soft
      tissues but not hard tissues.
AB  - Glycation induced crosslinking of connective tissue collagen is thought to be
      involved in the pathogenesis of various disorders associated with diabetes and
      aging. Although the formation of the glycation related collagen crosslinks
      appears to be universal for all tissues, currently it is unknown whether
      differences exist between soft and hard tissue biomechanics in response to
      glucose-mediated in vitro glycation. In this study, the impact of non-enzymatic
      glycation was investigated on tendons and bones, using them as models for soft
      and hard tissue respectively. Achilles tendons from rabbits, and femur and tibia
      from rats, were subjected to in vitro glycation with glucose. Sixty days
      following glycation, the matrix integrity of the tendons and bones was evaluated
      and compared with the respective non-glycated tissue (n=10 in each group). The
      results revealed that the impact of glycation was significant on the tendon but
      not on the bone. Measurements of the biomechanical stability of glycated tendons
      indicated a significant increase in maximum load (21%), Young's modulus of
      elasticity (72%), energy to yield (35%) and toughness (68%) compared to the non
      glycated tendons. No significant differences were found in breaking strength,
      bending stiffness, energy to yield and toughness between glycated and non
      glycated femurs or tibias. The deformation of both soft and hard tissue was
      unaffected by the glycation. Measurements at ultimate tissue failure (break
      point) revealed that glycated tendons bore significantly higher load and energy
      absorption than non-glycated tendons. In contrast, the deformation of the
      glycated tendons at break point was considerably reduced as compared to control
      tendons. However, glycation had no significant effects on the hard tissue
      biomechanical properties at break point. The results of this study demonstrate
      that in vitro glycation influences the biomechanical properties of soft tissue
      but not hard tissue.

PMID- 12798078
TI  - Acupuncture and arthroscopic acromioplasty.
AB  - BACKGROUND: Acupuncture alleviates acute and chronic shoulder pain. Yet it has
      not been determined whether acupuncture is useful following musculoskeletal
      surgery. HYPOTHESIS: Compared to sham acupuncture, arthroscopic acromioplasty
      subjects who received real acupuncture would manifest significantly better
      recovery as demonstrated by: UCLA shoulder scale, improved range of motion,
      diminished pain, decreased need and duration of analgesic use, and enhanced
      patient satisfaction. METHODS: Forty arthroscopic acromioplasty patients were
      randomized to real or sham acupuncture. UCLA shoulder scale scores, pain
      intensity, analgesic use, range of motion, and quality of life were monitored for
      four months. Data were analyzed with the general linear model ANOVA for repeated
      measures. RESULTS: Thirty-five subjects completed the study. Real acupuncture
      subjects scored significantly better on UCLA shoulder scale (p<0.000); pain
      intensity (p<0.022); self-reported analgesic use (p<0.008); angles of abduction
      (p<0.046); and in six of eight health status questionnaire components.
      CONCLUSIONS: Following arthroscopic acromioplasty, real acupuncture compared to
      sham acupuncture offered significantly greater improvement via: (1) lower pain
      level, (2) less analgesic use, (3) range of motion, and (4) patient satisfaction.

PMID- 12798077
TI  - Hyalgan has a dose-dependent differential effect on macrophage proliferation and
      cell death.
AB  - The intra-articular injection of high molecular weight hyaluronic acid (HA) has
      been reported to be an effective treatment for pain of osteoarthritis of the
      knee. However, the mechanism by which HA exerts its effect is unknown. To explore
      HA's influence on the growth of U937 human macrophages, cells were incubated for
      168 h with three concentrations, 1, 0.1 and 0.01 mg/mL, of Hyalgan, a high
      molecular weight HA preparation. At 24-h increments, the cells were examined for
      proliferation, cell cycle distribution as well as the number of apoptotic and
      dead cells. Exposing macrophages to 1 mg/mL Hyalgan significantly reduced the
      rate of cellular proliferation and altered the cell cycle distribution to yield
      decreased proportions of G0/G1 cells but increased S and G2/M cells.
      Concomitantly, a 10-fold increase in apoptotic cells and a 12-fold increase in
      dead cells were observed. The population doubling time (PDT) for cells treated
      with 1.0 mg/mL Hyalgan increased from 23.6 to 52.9 h. By contrast, the two lower
      Hyalgan concentrations significantly promoted macrophage proliferation in a dose
      dependent manner. They also increased the proportion of G2/M cells, but had no
      effect on the number of apoptotic or dead cells. The PDTs of 21.5 and 22.2 h were
      less than the control time of 23.6 h. These results demonstrate that Hyalgan
      concentrations have a differential effect on macrophage growth dynamics and
      suggest an anti-inflammatory effect at high HA concentrations.

PMID- 12798079
TI  - Health research in Papua New Guinea.
AB  - The Papua New Guinea Institute of Medical Research (PNGIMR) is one of the most
      respected health research institutions in the developing world, and its studies
      of the local health problems of PNG have consistently had international
      relevance. This article examines the structural and philosophical factors that
      have enabled the success of the PNGIMR, and presents the PNGIMR approach to
      research as a potential model for other disease-endemic countries. An overview of
      PNGIMR research into malaria and filariasis is given with selected examples as an
      introduction to a Trends in Parasitology series on health research in Papua New
      Guinea.

PMID- 12798080
TI  - Molecular parasitology of malaria in Papua New Guinea.
AB  - Research into the molecular biology of infectious diseases is mostly associated
      with well-developed countries. But in the midst of tropical Papua New Guinea,
      highly sophisticated molecular research has being conducted over years to
      understand and fight malaria and other tropical diseases. Here, we review such
      research carried out at the Papua New Guinea Institute of Medical Research. This
      Institute has considerably shaped research on molecular epidemiology through its
      analysis of the diversity and structure of the Plasmodium falciparum population.
      In addition, research has been conducted on human host factors and, more
      recently, the molecular analysis of drug resistance and the underlying molecular
      mechanisms of host-parasite interactions have been investigated.

PMID- 12798081
TI  - Erythrocyte polymorphisms and malaria parasite invasion in Papua New Guinea.
AB  - Plasmodium falciparum merozoites engage the erythrocyte surface through several
      receptor (host)-ligand (parasite) interactions during a brief exchange that
      results in parasite invasion of the red blood cell. Tens of thousands of these
      events occur during the initial cycle of blood-stage infections but advance
      towards billions as the parasite becomes visible to microscopists attempting to
      diagnose the underlying cause of illness in febrile patients. Advancing blood
      stage infection leads to massive proportions of erythrocytes that rupture during
      repetitive cycles of asexual reproduction. As the infection leads to illness, non
      immune or semi-immune individuals can suffer from life-threatening consequences
      of severe malarial anemia that play a leading role in pathogenesis. Through
      natural selection, some erythrocyte membrane polymorphisms are likely to have
      reduced the invasion success of the P. falciparum merozoite and increased the
      fitness of the human host population.

PMID- 12798082
TI  - The epidemiology of malaria in Papua New Guinea.
AB  - Papua New Guinea (PNG) is a patchwork of different ecological zones, inhabited by
      human populations of exceptional cultural and linguistic diversity. This results
      in complex variations in vector ecology and malaria epidemiology. Malaria is the
      main cause of morbidity in many health facilities in lowland areas, but it is
      absent in much of the highlands. All four human malaria species occur, but
      endemicity varies widely, with Plasmodium falciparum locally reaching holo
      endemic levels that are rarely found outside sub-Saharan Africa. The high
      frequency of Plasmodium vivax is an important difference to most African
      situations. PNG is therefore a prime location for studies of interactions between
      different parasite species, and of the biology of local human genetic adaptation
      and its implications for malaria morbidity and mortality.

PMID- 12798083
TI  - Lymphatic filariasis in Papua New Guinea: interdisciplinary research on a
      national health problem.
AB  - Bancroftian filariasis is a major public health problem in Papua New Guinea,
      where the level of transmission by the mosquito vector, human infection rates and
      clinical morbidity are among the highest in the world. Coordinated research
      efforts within the country, involving the disciplines of epidemiology, vector
      biology, immunology and genetics, have led to new insights into the ecology and
      pathogenesis of human lymphatic filariasis. Recent work using this knowledge base
      should be helpful in assessing local and global strategies aimed at eliminating
      Wuchereria bancrofti and in guiding research that will facilitate achievement of
      this goal.

PMID- 12798084
TI  - The malaria vaccine development program in Papua New Guinea.
AB  - Through a collaborative project led by the Papua New Guinea Institute of Medical
      Research (PNGIMR), Papua New Guinea has a significant role in the global effort
      to develop a malaria vaccine, ensuring that the malaria patterns in Asia and the
      Pacific region are considered in vaccine development strategies. Some of the
      major perspectives and achievements of the program are discussed here, one of the
      most successful being the trial of Combination B, a vaccine comprising three
      asexual blood-stage proteins [merozoite surface protein (MSP)1, MSP2 and ring
      infected erythrocyte surface antigen (RESA)], which led to a considerable
      reduction of parasite density in the immunized children.

PMID- 12798085
TI  - Cross-species regulation of Plasmodium parasitemia in semi-immune children from
      Papua New Guinea.
AB  - Malariologists have long been fascinated by the question of whether Plasmodium
      spp. interact in the human host. The first genetic study of the longitudinal
      dynamics of multiple Plasmodium spp. and genotypes in humans has been completed
      in Papua New Guinea, where all four Plasmodium spp. that infect humans are
      present. The broad implications of the data from this study are covered here and
      they show that the total parasite density of Plasmodium species oscillates around
      a threshold and that peaks of infection with each species do not coincide. It is
      proposed that malaria parasitemia is controlled in a density-dependent manner in
      these semi-immune children and that a cross-species mechanism of parasite
      regulation exists. A model of how multiple immune responses could act in concert
      to explain these within-host dynamics are discussed here in relation to observed
      epidemiological patterns of mixed-species infections.

PMID- 12798086
TI  - The buttressing coalition of the PNGIMR: an example of international
      collaborative research.
AB  - Good partnerships are based on mutual benefit. This also applies to international
      partnerships in medical research. The Papua New Guinea Institute of Medical
      Research (PNGIMR) has had many successful research collaborations, from which an
      interactive coalition has been built that is committed to supporting the PNGIMR
      without jeopardizing its integrity. This coalition also involves policy-makers
      from the Department of Health, teachers at the Medical School of Papua New Guinea
      and the Medical Research Advisory Committee of PNG. The PNGIMR's Buttressing
      Coalition supports research and training, but also assists the process of
      transferring research results into policy. The concept of "buttressing" is
      explored and the activities of the Buttressing Coalition are briefly described
      here. The idea of the Buttressing Coalition is a response from the international
      medical research community to globalization, and could be applied elsewhere,
      following the model developed in PNG.

PMID- 12798087
TI  - Engaging the community in research: lessons learned from the malaria vaccine
      trial.
AB  - When staff of the Papua New Guinea Institute of Medical Research first went into
      Wosera in 1979, to try and interest the community into participating in malaria
      research, the traditional warning sign of crossed bamboo sticks constantly
      blocked their path as they tried to enter the villages. In 2003, the site is a
      thriving research centre, with many projects under its belt, a successfully
      executed malaria vaccine trial to its credit, and approximately 13000 people from
      29 villages currently participating in demographic surveillance and various
      research projects. It has been a long road from community suspicion to
      sustainable community participation, and the field workers have learned many
      important lessons along the way that can be applicable to research programs in
      other disease-endemic areas.

PMID- 12798088
TI  - Qualitative hydrological and land-use planning tool for the Israel Coastal
      aquifer.
AB  - Due to a variety of past and present land-usages on the aquifer ground surface,
      appropriate groundwater management should consider anthropogenic activities on
      the ground surface and the potential of unsaturated zone media to convey water
      and pollutants to the aquifer. The objective of this paper is to present an
      approach which generates guidelines and recommendations which can lead to
      sustainable development. This method assesses the lithological characteristics of
      the aquifer's vadose zone, indicating potential rechargeability, while weighting
      factors leading to potential groundwater pollution resulting from some land-use.
      Recommendations regarding land-use planning and aquifer recharge can then provide
      a qualitative ecological tool towards sustainable groundwater management. Owing
      to its location, its critical significance to the country's fresh water supply,
      and its available field data, Israel's Coastal aquifer is employed here as the
      study area for implementation of this approach.

PMID- 12798089
TI  - A GIS-based fuzzy classification for mapping the agricultural soils for N
      fertilizers use.
AB  - Special attention should be paid to the choice of the proper N-fertilizer, in
      order to avoid a further acidification and degradation of acid soils and at the
      same time to improve nitrogen use efficiency and to limit the nitrate pollution
      of the ground waters. Therefore, the risk of leaching of the fertilizer and of
      the acidification of the soils must be considered prior to any N-fertilizer
      application. The application of N-fertilizers to the soil requires a good
      knowledge of the soil-fertilizer relationship, which those who are planning the
      fertilization policy and/or applying it might not have. In this study, a fuzzy
      classification methodology is presented for mapping the agricultural soils
      according to the kind and the rate of application of N-fertilizer that should be
      used. The values of pH, clay, sand and carbonates soil variables are estimated at
      each point of an area by applying geostatistical techniques. Using the pH values
      three fuzzy sets: "no-risk-acidification"; "low-risk-acidification"; and "high
      risk-acidification" are produced and the memberships of each point to the three
      sets are estimated. Additionally, from the clay and sand values the membership
      grade to the fuzzy set "risk-of-leaching" is calculated. The parameters and their
      values, which are used for the construction of the fuzzy sets, are based on the
      literature, the existing knowledge and the experimentation, of the soil
      fertilizer relationships and provide a consistent mechanism for mapping the soils
      according to the type of N-fertilizers that should be applied and the rate of
      applications. The maps produced can easily be interpreted and used by non-experts
      in the application of the fertilization policy at national, local and farm level.
      The methodology is presented through a case study using data from the Amfilochia
      area, west Greece.

PMID- 12798090
TI  - Assessment of occupational health hazards in scrap-tire shredding facilities.
AB  - Occupational hygiene conditions in scrap-tire shredding facilities were assessed
      to identify potential health risk factors for workers and provide a basis for
      developing future control measures. Specifically, noise, volatile organics and
      particulate levels were measured at two plants. Particulate/dust levels were
      measured via filter collection, and were analyzed gravimetrically. Sound pressure
      levels were measured and their spectral properties analyzed. Moreover, the major
      chemical species in the samples were identified using GC/MS. Finally, the
      mutagenic activity associated with the airborne particulates was assessed using a
      typical Ames test applied to Salmonella strains TA98 and TA100, with or without
      bio-activation. The noise levels were steady and high throughout the facilities,
      ranging from 85 to approximately 100 dBA. The octave band spectrum analysis
      reveals pattern similarity among the different areas. Levels of volatile organics
      were not significant, but a few mutagens/carcinogens, such as styrene,
      benzothiazole, phthalate ester and naphthalene were identified. Total particulate
      levels ranged from 0.43 to 6.54 mg/m(3), while respirable particulates were in
      the range 0.23-1.25 mg/m(3). Ames testing revealed indirect mutagenicity on
      strain TA98, indicating possible effects of frame-shift type mutagens. Chemical
      analysis of airborne particulates confirmed the presence of amines, aniline,
      quinoline, amides and benzothiazole, which are potentially convertible to frame
      shift type mutagenic nitrosoamines. Noise appears to be an occupational hazard
      for workers at scrap-tire shredding facilities, but the risk associated with the
      mutagenic/carcinogenic property of particulates requires further confirmation.

PMID- 12798091
TI  - Exposure to carbon monoxide in the Athens urban area during commuting.
AB  - An extensive survey has been designed to provide detailed information on carbon
      monoxide (CO) concentration in the main transport modes and along heavy traffic
      routes in the Athens urban area. Specifically the study identifies the main
      factors affecting CO exposure during commuting. Several portable, electrochemical
      CO monitors (Solomat's MPM4100), were used to record the in-vehicle CO
      concentrations every 15 s. Measurements were performed during rush hour periods.
      Field monitoring was conducted in summer 1998 and winter 1998-1999. Exposure
      estimates were compared to WHO guidelines. The findings showed that the mean CO
      level over trips of 30 min was 21.4 ppm for private car against 10.4, 9.6, 4 and
      11.5 ppm for bus, trolley, electric train and pedestrians, respectively.
      Transport mode, route, monitoring period and season had a significant influence
      on the measured CO concentrations. The study points out the importance of
      microenvironmental monitoring, instead of using fixed-site data in assessing
      commuter's CO exposure.

PMID- 12798092
TI  - Evaluation of vapor recovery systems efficiency and personal exposure in service
      stations in Mexico City.
AB  - Results of a field study on the efficiency of vapor recovery systems currently
      used in gasoline service stations in Mexico City are presented. Nine gasoline
      stations were studied, representing the several technologies available in Mexico
      City. The test was applied to a fixed vehicular fleet of approximately 10 private
      and public service vehicles. Each one of the gasoline service stations tested
      reported efficiencies above 80% in the recovery of vapor losses from gasoline
      which is the minimum permissible value by Mexican regulations. Implications to
      the emissions inventory are discussed. A second goal of this study was to measure
      the potential exposure of service attendants to three important components of
      gasoline: benzene; toluene; and xylenes. The influence of spatial location of
      personnel within the service station was also evaluated by measuring levels of
      the three compounds both at the refueling area and in the service station office.
      Results are discussed and compared to a previous study.

PMID- 12798093
TI  - Urban benzene exposure and oxidative DNA damage: influence of genetic
      polymorphisms in metabolism genes.
AB  - Benzene has been implicated as an environmental risk factor in leukaemia and
      other haematological diseases. Relationships between urban benzene exposure,
      oxidative DNA damage and polymorphisms in metabolism enzymes were examined in 40
      volunteers living and working in Copenhagen. Personal exposures to benzene,
      toluene and methyl tert-butyl ether (MTBE) were monitored during a 5-day period.
      DNA damage was measured by 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in
      lymphocyte DNA and urine and by comet assay with use of fapyguanine glycosylase
      (FPG) and endonuclease III (ENDO). Excretion of the benzene metabolites
      trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) were
      measured in urine. Polymorphisms in glutathione-S-transferases T1 (GSTT1), M1
      (GSTM1) and P1 (GSTP1) and NAD(P)H:quinone oxidoreductase (NQO) were determined.
      Median exposures to benzene, toluene and MTBE were 2.5, 18.7 and 0.86
      microg/m(3). No significant correlations between external benzene exposure and
      any of the biomarkers were found. However, a significant correlation between S
      PMA excretion and 8-oxodG in lymphocytes was found (R(s)=0.39). Men were found to
      excrete significantly more ttMA than the women did and ttMA excretion in men was
      found to be significantly associated with external benzene exposure (R=0.53,
      P=0.025). In addition, ttMA and S-PMA excretion was significantly higher in
      subjects with the NQO+/-genotype compared with subjects with the wild type
      (P=0.004 and P=0.011, respectively). Even though there are some limitations in
      this study due to the low range of benzene exposure and biomarker concentrations
      as well as a small number of subjects, these results could suggest that even at
      ambient concentrations exposure to benzene could have genotoxic effects in
      susceptible individuals.

PMID- 12798094
TI  - Concentrations of selected essential and non-essential elements in arctic fox
      (Alopex lagopus) and wolverines (Gulo gulo) from the Canadian Arctic.
AB  - Arctic fox (Alopex lagopus) and wolverine (Gulo gulo) tissues were collected in
      the Canadian Arctic from 1998 to 2001 and analyzed for various essential and non
      essential elements. Several elements (Ag, Al, As, B, Ba, Be, Co, Cr, Mo, Ni, Sb,
      Sn, Sr, Tl, U and V) were near or below the detection limits in >95% arctic fox
      and wolverine samples. Concentrations of Cd, Cu, Fe, total Hg (THg), Mn, Pb, Se
      and Zn were quantifiable in >50% of the samples analyzed and reported herein.
      Hepatic elemental concentrations were not significantly different among arctic
      foxes collected at Ulukhaqtuuq (Holman), NT (n=13) and Arviat, NU (n=50), but
      were significantly greater than concentrations found in wolverine liver from
      Kugluktuk (Coppermine), NU (n=12). The mean (+/-1 S.E.) concentrations of Cd in
      kidney were also significantly greater in arctic fox (1.08+/-0.19 microg g(-1)
      wet wt.) than wolverine (0.67+/-0.18 microg g(-1) wet wt.). However, mean hepatic
      Cu concentrations (Ulukhaqtuuq: 5.5+/-0.64; Arviat: 7.1+/-0.49 microg g(-1) wet
      wt.) in arctic foxes were significantly lower than in wolverines (32+/-3.3 microg
      g(-1) wet wt.). Hepatic total Hg (THg) concentrations in arctic fox from this
      study were not significantly different from specimens collected in 1973,
      suggesting that THg concentrations have not changed dramatically over the past 30
      years. The mono-methylmercury (MeHg) concentrations in selected (n=10) arctic fox
      liver samples from Arviat (0.14+/-0.07 microg g(-1) wet wt.) comprised 14% of
      THg. While the molar concentrations of THg were correlated with Se in arctic
      foxes and wolverines, the hepatic Hg/Se molar ratios were consistently lower than
      unity; suggesting that Se-mediated detoxification pathways of Hg are not
      overwhelmed at current exposure.

PMID- 12798095
TI  - Vitellogenin in carp (Cyprinus carpio) and perch (Perca fluviatilis):
      purification, characterization and development of an ELISA for the detection of
      estrogenic effects.
AB  - Vitellogenin (VTG), a phospholipoglycoprotein precursor of egg yolk is
      synthesized and secreted in the liver in response to circulating estrogens in
      female fish. Thus, the presence of VTG in male fish is a useful biomarker to
      identify estrogenic activity of natural or anthropogenic substances in sewage
      effluents. We report the purification of carp (Cyprinus carpio) and perch (Perca
      fluviatilis) VTG with the subsequent development and characterization of a
      specific ELISA for VTG measurement. VTG was purified by combination of ion
      exchange chromatography and size exclusion chromatography. The purified proteins
      were used as antigen for antibody production, as standard and tracer in the
      assay. Carp VTG was stable and showed a characteristic double band after Western
      blotting of the purified protein and in serum samples, respectively. In perch
      samples, several bands with lower molecular weight were present and appeared to
      be degradation products of VTG. The development of the carp VTG ELISA led to a
      sensitive and valid test system with inter-assay coefficients of variation
      between 3.0 and 12.3%. In contrast to carp, the described ELISA for perch VTG
      showed a much higher inter-assay variation up to 24%, possibly attributable to
      fast protein degradation. In conclusion, the described two-step chromatography is
      a simple purification method for VTG. Immunological and electrophoretical test
      systems are valid methods to determine VTG in some species like carp, but for
      other species like perch in which VTG is not stable, these methods are not
      applicable.

PMID- 12798096
TI  - Biomarkers of oxidative stress: a comparative study of river Yamuna fish Wallago
      attu (Bl. & Schn.).
AB  - Various oxidative stress biomarkers in gill, kidney and liver tissues in the
      Indian freshwater fish Wallago attu (Bl. & Schn.) were investigated. Fish were
      collected from two sites along the river Yamuna, which differ in their extent and
      type of pollution load. A comparison was made between the biomarker responses and
      general water chemistry at the two sites. The oxidative stress biomarkers that
      were analyzed included superoxide dismutase (SOD), catalase (CAT), xanthine
      oxidase (XOD) and glutathione redox cycle enzymes viz., glutathione peroxidase
      (GPx), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD).
      Levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were also
      evaluated. All biomarkers; SOD (P<0.001 in liver, kidney and gill), XOD (P<0.01
      in kidney and P<0.001 in liver and gill), GR (P<0.01 in liver, P>0.05 in kidney
      and P<0.001 in gill), G6PD (P<0.001 in liver, P>0.05 in kidney and P<0.01 in
      gill), GSH (P<0.001 in liver, kidney and gill) and LPO (P>0.05 in liver, kidney
      and gill) were found to be substantially higher in the fish collected from
      Panipat when compared with values in tissues of fish collected from Agra site.
      GPx and CAT showed a varied response. GPx activity was higher (P<0.001) in gills
      and kidney of the fish collected at Panipat site. However, liver showed
      significant low values (P<0.01) when compared with Agra site values. CAT activity
      was found to be significantly low, in both liver (P<0.01) and kidney (P<0.001)
      whereas in gills non-significant (P>0.05) low values were observed. Water
      chemistry data at two sites indicated that Panipat site with higher biochemical
      oxygen demand, chemical oxygen demand, pH and low dissolved oxygen was
      comparatively more polluted than Agra site. Industrial activity profile of both
      the sites also indicates that Panipat has vigorous industrial activity coupled
      with intensive use of chemicals in agricultural practices in Haryana state. The
      findings of the present investigation provide a rational use of oxidative stress
      biomarkers in aquatic ecosystem pollution biomonitoring. This is also the first
      such attempt reported from India.

PMID- 12798097
TI  - Lead poisoning combined with cadmium in sheep and horses in the vicinity of non
      ferrous metal smelters.
AB  - The diagnosis of lead poisoning combined with cadmium in sheep and horses living
      on farmland in the vicinity of non-ferrous metal smelters in Baiyin of Gansu
      province in China was based on laboratory findings as well as clinical signs. The
      concentrations of lead, cadmium, copper and zinc in soils, water, forages, feed
      and blood, hair and tissues of affected sheep and horses were determined in the
      surroundings of the smelters in Baiyin and controls. Haematological values were
      also measured. The concentrations of these elements in soils, forages, water and
      feed were significantly higher than those in the control area (P<0.01). The
      contents of lead and cadmium were 9.3 and 690 times in forages, respectively, 10
      and 35.6 times in feed. The concentrations of lead and cadmium in blood, hair and
      tissues of the affected sheep and horses were significantly higher than reference
      values and control animals (P<0.01). The occurrence of anaemia in affected
      animals belonged to a hypochromic and microcytic pattern. Lead and cadmium intake
      levels, estimated according to the ingestion rates of forages, illustrates that
      the apported lead and cadmium through the ingestion of vegetation growing in the
      closest sites to the smelters were approximately 6.0 mg Pb/kg body wt./day and
      1.1 mg Cd/kg body wt./day in horses, 21.4 mg Pb/kg body wt./day and 4.0 mg Cd/kg
      body wt./day in sheep, surpassing the fatal dosages for horses of 1.7 mg Pb/kg
      body wt./day and for sheep of 4.4 mg Pb/kg body wt./day and 1.0 mg Cd/kg body
      wt./day. It is, therefore, suggested that the disease of sheep and horses in this
      region is caused by lead poisoning combined with cadmium, mainly due to
      environment heavy metal pollution by industrial activity. Meanwhile, as such
      levels of contamination in animal food and grain pose a significant potential
      risk to human health, these results have formed the basis for subsequent research
      on levels of metal contamination in human tissues from affected populations.
      Thus, it can be seen that knowledge of lead and cadmium concentrations in
      livestock in this region is important for assessing the effects of pollutants on
      domestic animals themselves and contaminant intakes by humans.

PMID- 12798098
TI  - Effects of 17alpha-ethynylestradiol in a partial life-cycle test with zebrafish
      (Danio rerio): effects on growth, gonads and female reproductive success.
AB  - In this study, the impact of an exposure of zebrafish embryos (Danio rerio) until
      3 months post fertilization to 17alpha-ethynylestradiol (EE2: 0; 0,1; 1; 10; 25
      ng/l) was evaluated for growth and development, gonad development and body
      vitellogenin (VTG) content. After a recovery period of 5 months, the female
      reproductive success was evaluated. The results demonstrated a significant
      reduction in total body length, body weight, whole body Ca and P content and an
      increase in morphological abnormalities for fish exposed to 25 ng/l EE2 as a
      function of exposure time. An increase in total body VTG content was observed for
      fish exposed for a period of 3 months down to levels of 1 ng/l EE2. At the age of
      3 months, a dose-dependent increase of the number of fish with no macroscopic
      recognizable gonads was observed (up to 100% at 25 ng/l EE2). After a recovery
      period on clean tap water for 5 months, all fish had developed either ovaries or
      testis with a gonadosomatic index not different from control fish and the sex
      ratio was similar in EE2 treatment groups and controls. Nevertheless, a reduced
      number of spawning females and a reduced egg production were found for the female
      fish exposed to 10 or 25 ng/l EE2 for 3 months and which were allowed to recover
      for 5 months. Although the underlying mechanism could not be elucidated, these
      findings did indicate that the reproduction potential of fish populations might
      be disturbed by a long-term exposure to EE2 (> or =10 ng/l) from fertilization
      until sexual maturity.

PMID- 12798099
TI  - Nitrous oxide sources and sinks in coastal aquifers and coupled estuarine
      receiving waters.
AB  - Sources and sinks of the atmospherically reactive gas nitrous oxide (N(2)O) were
      determined in the heavily nutrient loaded Childs River in Cape Cod, MA. Surface
      waters were supersaturated and bottom waters were depleted with N(2)O throughout
      the system. In apparent septic effluent plumes, N(2)O concentrations reached 3
      orders of magnitude above atmospheric equilibrium. Because nitrate and N(2)O
      concentrations correlated in groundwater entering the estuary, septic tank
      effluent appeared responsible for the supersaturated concentrations of N(2)O in
      surface waters. A hyperbolic function fit nitrate and N(2)O concentrations in the
      water column of the estuary with a maximum supersaturation of approximately 60
      nM. From surface water supersaturation we predicted a release of 480 nmol N(2)O
      m(-2) h(-1) to the atmosphere in the summer. Property plots of salinity vs.
      bottom-water N(2)O suggested a benthic sink of N(2)O. Consistent with this trend,
      sediments consumed rather than released N(2)O in most flux measurements. Nutrient
      loading did not directly alter benthic N(2)O flux, potentially because
      stratification limited exposure of sediments to nitrate-rich surface waters, but
      macroalgal cover increased benthic N(2)O consumption. Sediment N(2)O consumption
      averaged 111 nmol N(2)O m(-2) h(-1) and correlated with oxygen uptake. Losses
      from the system to the atmosphere and sediments exceeded inputs of N(2)O
      contaminated groundwater, which suggests missing N(2)O sources.

PMID- 12798100
TI  - First national survey of atmospheric heavy metal deposition in Hungary by the
      analysis of mosses.
AB  - The atmospheric deposition of Cd, Cr, Cu, Fe, Ni, Pb, V and Zn in Hungary was
      investigated by using moss species as bioindicators. Our research was part of an
      international mapping project (Atmospheric Heavy Metal Deposition in Europe)
      [NORD 21 (1987) 1-44; NORD 9 (1994)] carried out in the most European countries
      in the 1990s to determine and to compare atmospheric heavy metal background
      pollution by standardized methods. Sampling was performed at 116 sites
      distributed over Hungary in the autumn of 1997. Moss species of Hypnum
      cupressiforme (72.4%) were preferred. But where it could not be collected, other
      species were taken. Unwashed, dried samples were digested with H(2)O(2)/HNO(3),
      and the concentrations of heavy metals were determined by ICP-AES. The results
      reflect local emission points. Background mean levels of Cd, Fe and Ni were
      mildly elevated in comparison to European means [NORD 9 (1994)]. Probably, that
      was due not only to pollution, but to the use of Hypnum cupressiforme, which can
      accumulate higher concentrations of heavy metals compared to other species. The
      results are presented on colored contour maps obtained with the SURFER program
      (Golden Software Inc. Co).

PMID- 12798101
TI  - 129I in Swedish rivers: distribution and sources.
AB  - We analyzed the concentration of 129I in the water of 26 rivers covering most of
      the runoff from Sweden, with the aim of assessing current contamination levels,
      distribution patterns and potential sources in freshwater systems of northern
      Europe. The results show relatively high values (up to 1.4 x 10(9) atoms l(-1)),
      steeply decreasing levels with increasing latitude and a positive correlation
      with Cl concentration and other chemical parameters. The 129I concentrations
      observed in south Sweden are probably the highest ever recorded in rivers without
      any direct discharge from a nuclear installation. The strong latitudinal
      dependence suggests a northward dilution and possibly depletion of the isotope
      and a transport from a source located to the south. The most plausible source of
      the 129I in the studied rivers is atmospheric fallout of 129I emitted either by
      atmospheric discharges from the nuclear reprocessing facilities at Sellafield
      (England) and La Hague (France) or by volatilization from seawater contaminated
      by the same sources. The question is now whether and at what rate the 129I
      concentration in Nordic watersheds will increase further if discharges from
      nuclear reprocessing continue.

PMID- 12798102
TI  - Impact of chromated copper arsenate (CCA) in wood mulch.
AB  - The production of landscape mulch is a major market for the recycling of yard
      trash and waste wood. When wood recovered from construction and demolition (C&D)
      debris is used as mulch, it sometimes contains chromated copper arsenate (CCA)
      treated wood. The presence of CCA-treated wood may cause some potential
      environmental problems as a result of the chromium, copper, and arsenic present.
      Research was performed to examine the leachability of the three metals from a
      variety of processed wood mixtures in Florida. The mixtures tested included mixed
      wood from C&D debris recycling facilities and mulch purchased from retail
      outlets. The synthetic precipitation leaching procedure (SPLP) was performed to
      examine the leaching of chromium, copper and arsenic. Results were compared to
      Florida's groundwater cleanup target levels (GWCTLs). Eighteen of the 22 samples
      collected from C&D debris processing facilities leached arsenic at concentrations
      greater than Florida's GWCTL of 50 microg/l. The mean leachable arsenic
      concentration for the C&D debris samples was 153 microg/l with a maximum of 558
      microg/l. One of the colored mulch samples purchased from a retail outlet leached
      arsenic above 50 microg/l, while purchased mulch samples derived from virgin
      materials did not leach detectable arsenic (<5 microg/l). A mass balance approach
      was used to compute the potential metal concentrations (mg/kg) that would result
      from CCA-treated wood being present in wood mulch. Less than 0.1% CCA-treated
      wood would cause a mulch to exceed Florida's residential clean soil guideline for
      arsenic (0.8 mg/kg).

PMID- 12798103
TI  - Natural contamination with arsenic and other trace elements in ground waters of
      Argentine Pampean Plain.
AB  - Natural contamination with arsenic and other toxic trace elements was studied on
      a 50,000 km(2) area of the Pampean Plain in Argentina. The locations where
      natural sources of arsenic are considered to be of concern continue to grow, and
      include those associated with soils developed on loess or loessic sediments zones
      and transported volcanic materials sites. Contents of total arsenic, vanadium,
      chromium, iron and barium higher than those recommended as maximum allowable
      levels in drinking waters have been measured. In the case of arsenic, analyses of
      raw groundwaters yielded levels as high as 600 microg As/l. Reported data are
      discussed in connection with geological and environmental processes involved in
      ground water contamination.

PMID- 12798104
TI  - Short-term tests with a pilot sewage plant and biofilm reactors for the
      biological degradation of the pharmaceutical compounds clofibric acid, ibuprofen,
      and diclofenac.
AB  - The biodegradation of three active compounds of pharmaceuticals clofibric acid,
      ibuprofen, and diclofenac was investigated in short-term tests with a pilot
      sewage plant (PSP) and biofilm reactors (BFR, oxic and anoxic) as model systems
      for municipal sewage treatment. The PSP was characterized with respect to mixing
      behavior, the BFR with respect to biofilm content and sorption of the
      pharmaceutical compounds. The short-term experiments were carried out for 55 h in
      the PSP and for 48 h in the BFR. The concentration of the pharmaceuticals was in
      the microgram per liter range in presence of readily biodegradable substances in
      the milligram per liter range. Therefore, a too short time period and too low
      concentration to promote adaption of the microorganisms were applied. Under the
      operating conditions applied the biodegradation of the lipid lowering agent
      clofibric acid and the analgesic agents ibuprofen and diclofenac in the oxic BFR
      resembled that in the PSP. Clofibric acid and diclofenac were not eliminated and
      reached a level of approximately 95% of their initial concentration, whereas the
      concentration of ibuprofen was decreased to approximately 40% in the PSP and to
      approximately 35% in the oxic BFR. Both systems showed, therefore, an inherent
      ability for ibuprofen biodegradation. Elimination in the anoxic BFR resulted in a
      decrease of the concentration of all three substances to values between 60 and
      80% of their initial concentration. In contrast to the PSP acetone revealed as
      inhibitor in the BFR. In both systems acetone was not degraded in the short-term
      tests.

PMID- 12798105
TI  - Runoff erosion and nutrient depletion in five Mediterranean soils of NE Spain
      under different land use.
AB  - We investigated the influence of agricultural management and various plant covers
      related to the period of abandonment on soil properties, erosion and nutrient
      depletion in a typical Mediterranean area with sandy loam shallow soils.
      Cultivated soils (CS) with insufficient management, 5 year abandoned soils
      covered with meadow (A5), 25 year abandoned soils covered with dense scrubs
      (A25), 50 year abandoned soils covered with cork trees (A50) and soils in a 50
      year pine reforested area (P50) were studied over a period of 6 months (May
      October 1999). The soils were classified as Lithic Xerorthents. Both the
      differences in soil properties and response to rainfall events were mainly
      attributed to the different vegetation types and stages in land management.
      Principal components analysis (PCA) was performed on the results, by running the
      overall data determined after five rainfall events. The factors extracted by PCA
      of the samples by variables matrix represented the response of the environments
      to different rainfall intensities as a function of management or natural
      evolution after abandonment. CS environments showed the highest runoff and
      sediment yield as well as the highest amount of dissolved organic carbon (DOC)
      and nitrogen in runoff water. The sequence of abandonment (A5, A25 and A50)
      showed approximately the same runoff production, whereas eroded sediments (ES)
      and DOC were inversely correlated. Organic carbon in the ES and DOC in runoff
      water always increased with the period of abandonment, which accounted for
      consistent nutrient depletion. Nevertheless, the A50 environment (dominated by
      Quercus suber) showed the best soil properties, whilst the A25 environment with
      dense cover of Cistus monspeliensis and Calicotome espinosa seemed to cause a
      worsening effect on the soil's physical and chemical properties. This is probably
      because these environments are more severely damaged by wild fire occurrence. In
      terms of sediment yield, the P50 environment followed CS environment, indicating
      that reforestation followed by insufficient forest management may negatively
      affect both soil properties and response to the erosive action of rainfall.

PMID- 12798106
TI  - Distribution and bioavailability of copper in farm effluent.
AB  - Effluent and sludge samples from a number of dairy and piggery units in the North
      Island of New Zealand were collected and analysed for free ionic-copper (Cu(2+))
      and organically-complexed Cu. The bioavailability of sludge-Cu was examined using
      microbial respiration and plant growth experiments. Microbial respiration was
      measured at various levels of Cu (0-1000 mg kg(-1)), added as copper sulfate
      (CuSO(4)) and sludge-Cu, using a Gilson differential respirometer. A glass house
      experiment was conducted to examine the transformation of Cu in soils and its
      subsequent uptake by ryegrass pasture. Three Cu sources were used that included
      fast-release CuSO(4), slow-release copper oxide (CuO) and Cu-enriched sludge. The
      pasture samples were analysed for Cu concentration. The transformation of Cu in
      the soil was monitored by analysing the soil samples for various fractions of Cu.
      The effluent and sludge samples collected from farms which regularly used Cu to
      treat lameness in dairy cattle and as a growth promoter in swine contained higher
      concentration of Cu. The total Cu concentration ranged from approximately 0.1 to
      1.55 mg l(-1) and from 0.5 to 10.5 mg l(-1) in the piggery and diary effluent,
      respectively. The corresponding values for the sludge samples were 3.0-526 and 25
      105 mg kg(-1). Most of the Cu in both the effluent and solid sludge material was
      organically complexed. The respiration measurements indicated that sludge-Cu was
      less toxic to soil microbial activity than CuSO(4). The results from the glass
      house experiment indicated that increasing the level of Cu applied through
      fertilisers and sludge increased Cu concentration in plants. At the same rate of
      application, plants took up less Cu from sludge and CuO than from CuSO(4). There
      was, however, a greater translocation of Cu from root to shoot at the highest
      rate of Cu through sludge application. The Cu fractionation study indicated that
      there was greater accumulation of organic bound Cu in the sludge-treated soil
      than the fertiliser-treated soil.

PMID- 12798107
TI  - Optical and chemical characteristics of the atmospheric aerosol in four towns in
      southern Poland.
AB  - The absorption coefficient a(p) [m(-1)] as well as the mass absorption
      coefficient sigma(p) [m(2)/g] has been estimated for PM10 and PM2.5 in four towns
      located in southern Poland, based on the assumption that the reflectance of
      aerosol-laden filters is a good proxy for the absorptivity of aerosols. The
      optical properties of the airborne particles were also compared with their
      surface composition obtained by photoelectron spectroscopy (XPS). It was found
      that coarse particles, which constituted 20-30% of PM10, exhibited insignificant
      contribution to the absorption. The most absorptive aerosols were found in the
      towns located in Upper Silesia, a highly industrialized area. This reflects both
      the relative content of carbon in PM2.5 and the mass concentration of the fine
      mode. It was found that oxides and sulfates play an important role in promoting
      the reflectance of light from aerosols in the winter. These results support the
      suggestion that the revision of existing air quality standards for particulate
      pollution is needed.

PMID- 12798108
TI  - Micronuclei in lymphocyte subsets in relation to plasma mercury, dental amalgam
      and acrylate-containing tooth fillings.

PMID- 12798109
TI  - Mapping of 137Cs deposition over eastern France 16 years after the Chernobyl
      accident.
AB  - We observed the relationship between present-day 137Cs surface activity and the
      rainfall in May 1986 to establish a relevant map of 137Cs deposition over eastern
      France. This study was performed in an area of the lower Rhone valley where
      clayey soils are assumed to trap caesium efficiently. Based on the
      rainwater/airborne activity ratio deduced from this relationship, we verified
      that present-day activities, measured in clayey soils of this type, are
      relatively representative of the initial depositions. The interlocked
      contaminated areas of the resulting map can be related to rainfall occurrences,
      as is the case for all countries affected by the Chernobyl fallout. This map can
      be reasonably compared with those obtained for countries bordering France in
      terms of both activity levels and extent of homogeneous activity areas. Lastly,
      we demonstrate that it would not be possible to produce a coherent map of initial
      fallout by extending the campaign over the whole of the eastern territory based
      on present-day soil activity measurements alone. Hence, only the relationship
      between 137Cs deposition and the rainfall of the first week of May 1986 can be
      used to construct a map depicting the Chernobyl fallout over eastern France.

PMID- 12798111
TI  - Evaluation of bottom ash and composted manure blends as a soil amendment
      material.
AB  - The long-term goal of this project was to find alternative uses for bottom ash
      (BA) and composted dairy manure (CM), by-products of coal combustion and
      livestock production, respectively. The study discussed in this paper focused on
      potential water quality impacts associated with using blended BA and CM as a soil
      amendment. The constituents of BA and CM include heavy metals and other chemicals
      that, while essential nutrients for plant growth, also pose a potential threat to
      water quality. Four blends (BA:CM, v/v) namely, B1 (100%:0%), B2 (70%:30%), B3
      (50%:50%) and B4 (0%:100%), were subjected to flow-through water table management
      and two blends, B2 (70%:30%) and B3 (50%:50%), were subjected to constant head
      water table management using de-ionized water. Leachate and standing water from
      saturated and flooded blends of BA and CM were examined for total solids (TS),
      volatile solids (VS), COD, pH, total Kjeldahl nitrogen (TKN), NO(3)-N, total P,
      total K as well as selected metals over a 5 and 7 week period for flow-through
      and constant head watertables, respectively. The results showed that higher CM
      content resulted in higher TS, VS, TKN, P and K concentrations in the leachate
      and standing water. Concentrations of these constituents were higher in leachate
      than in the standing water. Even though, marked reductions of most chemicals in
      the leachate and standing water were realized within one to three weeks,
      initially high concentrations of chemicals in leachate and standing water from
      these particular blends made them unsuitable as soil amendment material. Based
      upon these results, it was concluded that additional column studies of BA and CM
      blends with reduced CM content (5%, 10% and 20%) should be performed to further
      assess the feasibility of BA and CM blends as an environmentally safe soil
      amendment material.

PMID- 12798112
TI  - Struvite precipitation in anaerobic swine lagoon liquid: effect of pH and Mg:P
      ratio and determination of rate constant.
AB  - Because of increased concern about surface water eutrophication from nutrient
      enriched agricultural runoff, many swine producers are encouraged to decrease
      application rates of waste-based P. Precipitation and subsequent removal of
      magnesium ammonium phosphate (MgNH(4)PO(4) x 6H(2)O), commonly known as struvite,
      is a promising mechanism for N and P removal from anaerobic swine lagoon
      effluent. The objectives of this research were to (i) quantify the effects of
      adjusting pH and Mg:P ratio on struvite precipitation and (ii) determine the rate
      constant pH effect for struvite precipitation in anaerobic swine lagoon liquid.
      Concentrations of PO(4)-P in liquid from two anaerobic swine lagoons were
      determined after 24 h of equilibration for a pH range of 7.5-9.5 and Mg:P ratios
      between 1:1 and 1.6:1. Struvite formation reduced the PO(4)-P concentration in
      the effluents to as low as 2 mgl(-1). Minimum concentrations of PO(4)-P occurred
      between pH 8.9 and 9.25 at all Mg:P ratios. Struvite precipitation decreased
      PO(4)-P concentrations by 85% within 20 min at pH 9.0 for an initial Mg:P ratio
      of 1.2:1. The rate of PO(4)-P decrease was described by a first-order kinetic
      model, with rate constants of 3.7, 7.9, and 12.3 h(-1) at pH 8.4, 8.7 and 9.0
      respectively. Our results indicate that induced struvite formation is a
      technically feasible method to remove N and P from swine lagoon liquid and it may
      allow swine producers to recover nutrients for off-farm sale.

PMID- 12798113
TI  - Effects of glucose overloading on microbial community structure and biogas
      production in a laboratory-scale anaerobic digester.
AB  - This study characterizes the response of the microbial communities of a
      laboratory-scale mesophilic biogas process, fed with a synthetic substrate based
      on cellulose and egg albumin, to single pulses of glucose overloading (15 or 25
      times the daily feed based on VS). The microbial biomass and community structure
      were determined from analyses of membrane phospholipids. The ratio between
      phospholipid fatty acids (PLFAs; eubacteria and eucaryotes) and di-ethers (PLEL;
      archaea) suggested that methanogens constituted 4-8% of the microbial biomass.
      The glucose addition resulted in transient increases in the total biomass of
      eubacteria while there were only small changes in community structure. The total
      gas production rate increased, while the relative methane content of the biogas
      and the alkalinity decreased. However, the biomass of methanogens was not
      affected by the glucose addition. The results show that the microbial communities
      of biogas processes can respond quickly to changes in the feeding rate. The
      glucose overload resulted in a transient general stimulation of degradation rates
      and almost a doubling of eubacterial biomass, although the biomass increase
      corresponded to only 7% of the glucose C added.

PMID- 12798114
TI  - Utilization of tigernut (Cyperus rotundus, L.) meal in diets for cockerel
      starters.
AB  - The effect of feeding graded levels of tigernut meal (TGN) as a replacement for
      maize in the diets of cockerel starters on carcass characteristics and economics
      of feed conversion was assessed for 70 days. Tigernut replaced maize at 0%,
      33.33%, 66.67% and 100% levels. A total of 120 day-old chicks were randomly
      allotted to four experimental diets such that each dietary treatment had three
      replicates of ten birds. Inclusion of TGN at 33.33% in cockerel diets supported
      better carcass yield in terms of high plucked, eviscerated, drumstick, thigh,
      neck, wing, heads, shanks, livers, hearts and lung weights without significant
      differences (P>0.05) in values obtained. However, there were significant
      difference (P<0.05) in back, breast, abdominal fat, gizzard, spleen, kidney and
      intestinal weights and lengths. Inclusion of TGN 100% level significantly
      depressed parameters assessed. The optimum replacement level of maize with TGN
      was 33.33% as this gave no significant reduction in carcass yield of the birds
      but a significant reduction in the cost of feed consumed. It required a feed cost
      of 42.90 ( 0.31 US dollars) to produce one kilogram weight gain on diet 2
      (33.33%). Inclusion of TNG in the diets resulted in feed cost savings of 4.88%
      (D2), 8.17 (D3) and 8.90% (D4) respectively.

PMID- 12798115
TI  - Characterization of an Escherichia coli lysA insertion targeted mutant using
      phenotype arrays.
AB  - The objective of this study was to investigate the effect of a lysine
      biosynthesis insertion mutation on the growth response and phenotype of
      Escherichia coli. The lysA gene encodes the last enzyme in the lysine
      biosynthetic pathway in most bacteria. This E. coli insertion mutant exhibited
      altered growth physiology and phenotype of the recipient E. coli. The constructed
      mutant could grow in the absence of lysine supplementation although the extent of
      growth after 7 h incubation in the presence of most lysine concentration was
      significantly (p<0.05) decreased compared to that observed with the parent E.
      coli strain. The mutant was also less able to utilize carbon and nitrogen
      substrates than the parent E. coli strain as determined by using phenotype
      arrays. These results suggest that the carbon and nitrogen phenotype profiles of
      E. coli when measured on phenotype arrays are altered after targeted insertion
      mutagenesis in the lysA gene. Creation of altered phenotypes may have potential
      for pharmaceutical and biotechnological applications of lysine E. coli
      metabolism.

PMID- 12798116
TI  - Granule development in a split-feed anaerobic baffled reactor.
AB  - Operating anaerobic reactors at high organic loading rates during start-up can
      lead to instability, accumulation of volatile fatty acids and low pH, such
      problems being exacerbated in reactors that exhibit plug-flow characteristics.
      Moreover, plug-flow conditions increase the exposure of biomass to any toxic
      components in the feed. To overcome these limitations, an anaerobic baffled
      reactor (ABR), a reactor exhibiting partial plug-flow characteristics, was
      modified by splitting the feed between the individual compartments to produce the
      split-feed ABR (SFABR). Consequently, more favourable conditions were created in
      the initial compartments, such as lower, longer hydraulic retention time and
      longer cell retention time; conditions in the final compartments were also
      improved by the increased food availability for microorganisms. Other benefits
      included better gas mixing characteristics as a result of the more balanced gas
      production across the reactor. Granule development was compared in SFABR and
      normally fed ABR by analysing sludge samples, taken during start-up and
      continuous operation, using scanning electron microscopy. Photomicrographs
      allowed tentative conclusions to be made concerning the effect of split-feeding
      on the distribution of bacterial populations within the granule architecture and
      the role of extracellular polymers on granule formation.

PMID- 12798117
TI  - Biological treatments affect the chemical composition of coffee pulp.
AB  - Biological treatments were applied to fresh coffee pulp (CoP) to improve its
      nutritive value for monogastric animals by reducing its content of cellulose and
      antinutritional factors (ANFs) such as total phenols, tannins and caffeine.
      Treatments were: (1) ensiling with 0, 50 and 100 gkg(-1) molasses for 2 and 3
      months, (2) aerobic decomposition for 0, 7, 14, 21, 28, 35 and 42 days, (3)
      aerobic bacterial inoculation (Bacillus sp.) for 0, 7, 14, 21 and 28 days.
      Ensiled CoP (E-CoP) showed higher fat and ash contents than oven-dried-CoP (OD
      CoP; P<0.05). Similarly, true protein values tended to increase. The cellulose
      and total phenols levels of E-CoP were lower than OD-CoP (P<0.05). The E-CoP
      tannins levels tended to be lower than OD-CoP whereas caffeine levels remained
      unaffected. Improvement in the nutritional quality of E-CoP was associated with
      higher fat and protein contents and reduction of cellulose, total phenols and
      tannins. The aerobic decomposition treatment improved the nutritional quality of
      CoP by increasing true protein and fat contents. In addition, total phenols,
      tannins, caffeine and cellulose contents were reduced by an increase in treatment
      time (P<0.05). Bacterial treatment increased the protein content of CoP after 21
      days (from 137 to 392 gkg(-1)) and decreased it after 28 days. Cellulose, total
      phenols, tannins and caffeine contents reduced with an increase in time of
      bacterial degradation. Bacterial treatment improved the CoP quality by increasing
      protein content and reducing cellulose and ANFs, especially after 21 days of
      treatment. Both the aerobic decomposition (after 21-28 days) and the aerobic
      bacterial degradation of CoP (after 21 days) appeared more suitable to improve
      the nutritional quality of CoP than the ensiling.

PMID- 12798118
TI  - Biomass accumulation and carbon utilization in layered sand filter biofilm
      systems receiving milk fat and detergent mixtures.
AB  - This research evaluated utilization of organic compounds and biomass accumulation
      in three different layered sand filter biofilm systems renovating a mixture of
      detergent and milk fat. Organic compounds were measured as chemical oxygen demand
      (COD) and biomass as ATP. A two-layer sand filter with coarse sand on the top and
      fine sand at the bottom; a three-layer sand filter with pea gravel on the top,
      coarse sand in the middle, and fine sand at the bottom; and a two-filters in
      series sand filter biofilm system each received mixtures of butterfat and
      detergent. While the three-layer sand filter system had greater COD utilization
      capacity due to a longer filter run, the two-filters in-series sand filter system
      had greater COD utilization efficiency. The COD utilization was highly associated
      with the period of filter run to clogging. The decrease of COD utilization rate
      could lead to the clogging of sand filters. To maintain long filter runs without
      clogging, a COD loading rate of 2100 mg O(2)/m(2)/h was recommended for three
      layer sand filters and 1800 mg O(2)/m(2)/h for two-layer sand filters for high
      fat content wastewater. In the two-layer sand filters and the three-layer sand
      filters, biomass did not seem to accumulate in any particular layer on a unit
      volume of sand. However, based on unit surface area, the coarse sand layer
      accumulated more biomass than the fine sand layer and the pea gravel layer.

PMID- 12798119
TI  - Kinetics of biosorption of cadmium on Baker's yeast.
AB  - In the present study the kinetics of biosorption of cadmium(II) ions by
      deactivated protonated yeast converted to sodium form was investigated for
      different initial concentrations of the metal ion (10-100 ppm) and different
      sorbent dosages (0.1-2.0 g) at a pH of 6.5. The adsorption process occurred in
      four distinct steps and the rates for these steps decreased sequentially. The
      rate of cadmium uptake in each case was pseudo-second-order with respect to metal
      ion concentration. The amount sorbed at equilibrium was found to be directly
      proportional to the initial metal ion concentration divided by the sorbent mass.

PMID- 12798120
TI  - Carboxymethylcellulose from totally chlorine-free-bleached milox pulps.
AB  - High purity cellulose pulp was obtained from Eucalyptus globulus wood by using an
      environmentally friendly delignification technique (Milox pulping) and subsequent
      bleaching by totally chlorine free technology. The pulp obtained under optimised
      experimental conditions was used for the manufacture of carboxymethylcellulose in
      a heterogeneous medium. By means of an experimental design, the effects of
      selected operational variables on the composition and chemical properties of
      reaction products from the carboxymethylation reaction were assessed for
      optimisation purposes. The distribution of the different carboxymethylglucose
      mole fractions (un-, mono-, di- and tri-substituted) was determined and compared
      with theoretical predictions. The maximum average degree of substitution (1.26)
      was determined at a NaOH/cellulose mole ratio of 4.8 and at a MCA/cellulose mole
      ratio of 2.0.

PMID- 12798122
TI  - Slow pyrolysis of wood barks from Pinus brutia Ten. and product compositions.
AB  - Biomass in the form of pine bark (Pinus brutia Ten.) was pyrolysed in an
      externally heated fixed-bed reactor. The effects of temperature and heating rate
      on the yields and compositions of the products were investigated. Pyrolysis runs
      were performed using reactor temperatures between 300 and 500 degrees C with
      heating rates of 7 and 40 degrees Cmin(-1). The product yields were significantly
      influenced by the process conditions. The bio-oil obtained at 450 degrees C, at
      which the liquid product yield was maximum, was analysed. It was characterized by
      Fourier transform infrared spectroscopy. In addition, the solid and liquid
      products were analysed to determine their elemental composition and calorific
      value. Chemical fractionation of bio-oil showed that only low quantities of
      hydrocarbons were present, while oxygenated and polar fractions dominated. The
      empirical formula of the bio-oil with heating value of 31.03 MJkg(-1) was
      established as CH(1.43)O(0.332)N(0.0013).

PMID- 12798121
TI  - Effects of pulp mill solids and three composts on early growth of tomatoes.
AB  - Compost has been proposed as a means of simultaneously diverting organic
      materials from landfills while producing a valuable product that improves tilth,
      organic matter content and nutrient supply of agricultural soils. Composts
      manufactured from different source materials may have markedly different
      properties however, even if they meet all regulatory requirements. We compared
      the capacity of composts made from three different combinations of organic wastes
      (horse manure and bedding, mink farm wastes, municipal solid waste (MSW) and
      sewage sludge) along with clarifier solids from a chemo-thermomechanical pulp
      mill, to enhance the growth of tomato (Lycopersicon esculentum L.) seedlings
      grown in nutrient-poor organic potting soil. Germination and seedling emergence
      of tomatoes, cress (Lapidium sativum L.) or radish (Raphanus sativus L.) were
      tested to assess phytotoxicity of the four amendments. Mink farm compost and
      horse manure compost stimulated root and shoot growth of tomato seedlings but MSW
      compost and pulp mill solids were strongly inhibitory. MSW compost and unamended
      potting soil also inhibited seedling emergence and pulp mill solids produced
      stunting and deformities in radish and cress seedlings. Both toxic constituents
      and nutrient imbalances may be responsible for the growth-inhibiting effects of
      these amendments. Application of pulp mill solids to agricultural soil without
      composting may lead to deleterious effects on vegetable crops.

PMID- 12798123
TI  - Growth kinetics response of a Salmonella typhimurium poultry marker strain to
      fresh produce extracts.
AB  - The purpose of this research was to assess growth response of a Salmonella
      typhimurium poultry marker strain to fresh homogenized vegetables. Salmonella
      growth rates were significantly higher (p<0.05) in jalapeno extracts than any
      other produce extract examined. Growth rates on samples of broccoli and lettuce
      extracts were greater (p<0.05) than the respective growth rates on bell pepper
      and tomato. Broccoli extracts yielded the highest extent of growth (4 h optical
      density) followed by jalapeno and bell pepper extracts. From this study, it
      appears that fresh produce extracts have different abilities to significantly
      alter growth response in Salmonella. This could potentially be explained by the
      variations of pH, nutrient availability to the bacteria, or unknown components
      found within fresh produce.

PMID- 12798124
TI  - Comment on "Biosorption of chromium(VI) from aqueous solution by cone biomass of
      Pinus sylvestris".

PMID- 12798125
TI  - An ultrastructural study of connective tissue in mollusc integument III.
      Cephalopoda.
AB  - We studied structure and ultrastructure of the subepidermal connective tissue
      (SEC) of the integument of three cephalopods (Sepia officinalis, Octopus vulgaris
      and Loligo pealii). In all species, three distinct regions of the SEC were
      recognised: (a) an outer zone (OZ) that included the dermal-epidermal junction,
      and consisted of a thin layer of connective tissue containing muscles, (b) an
      extensive middle zone (MZ) containing a compact network of collagen fibres and
      numerous cells, (c) an inner zone (IZ) of loose connective tissue that merged
      with muscular fascia. This arrangement differs from that in bivalves and
      gastropods and recalls vertebrate integument. The dermal-epidermal junction of
      cephalopods differed from that of bivalves, gastropods and mammals in that the
      epidermal cells did not possess hemidesmosomes, and their intermediate filaments
      terminated directly in the plasmamembrane. The thick (120-500 nm) basal membrane
      (BM) had a superficial zone containing a regular array of granules; a lamina
      densa composed of a compact network of small filaments and granules; and an IZ
      distinguished by expansions of granular material protruding into underlying
      structures. Collagen fibres contained fibroblast-derived cytoplasmic thread,
      running through their centres and were surrounded by granular material that joins
      them to adjacent fibres. The collagen fibrils were of medium diameter (30-80 nm)
      had the typical ultrastructure of fibrillar collagens, and were surrounded by
      abundant interfibrillar material. The hypodermis was loose, with a network of
      small bundles of collagen fibrils. Cephalopod integument appears to represent a
      major evolutionary step distinguishing this class of molluscs.

PMID- 12798126
TI  - Immunocytochemical characterization of adenohypophyseal cells in the greater
      weever fish (Trachinus draco).
AB  - The adenohypophysis of the greater weever fish (Trachinus draco) was studied
      using histochemical and immunocytochemical methods. The adenohypophysis comprised
      the rostral pars distalis (RPD), the proximal pars distalis (PPD), and the pars
      intermedia (PI). Neurohypophysis showed a patent hypophyseal stalk which was
      divided into several branches intermingled with the adenohypophysis. Salmon
      prolactin (PRL)-immunoreactive (ir) cells, arranged in follicles, resided in the
      RPD and the most rostral part of the ventral PPD. Human adrenocorticotropin
      (ACTH)-ir cells were located in the RPD between PRL-ir cells and the
      neurohypophyseal processes. Salmon and seabream somatotropin (GH)-ir cells were
      located in both the dorsal and the ventral PPD. Some GH-ir cells were seen in
      surrounding and in contact with neurohypophyseal branches, whereas other isolated
      or clustered GH-ir cells were embedded in adenohypophyseal cells of the PPD. In
      addition, isolated or clustered GH-ir cells were also detected in the tissue of
      the PPD covering the most rostral part of PI. Only one class of salmon and carp
      gonadotropin (GTH)-ir cells was detected. Isolated or clustered GTH-ir cells
      resided in both the dorsal and the ventral PPD and were seen surrounding the PI
      and in the tissue of the PPD covering the most rostral part of PI. In addition, a
      few scattered GTH-ir cells were observed in the ventral RPD. Scattered groups of
      thyrotropin (TSH)-ir cells were present in the anteroventral PPD. Salmon and
      seabream somatolactin (SL)-ir and bovine melanotropin (MSH)-ir cells were
      intermingled surrounding the neurohypophyseal tissue. SL-ir cells were negative
      to periodic acid-Schiff technique. MSH-ir cells showed a very weak
      immunoreactivity to anti-human ACTH((1-24)) serum. In addition to the PI
      location, few isolated or clustered SL- and MSH-ir cells were observed in the
      dorsal PPD.

PMID- 12798127
TI  - Muscle growth in Nile tilapia (Oreochromis niloticus): histochemical,
      ultrastructural and morphometric study.
AB  - Muscle growth in Nile tilapia (Oreochromis niloticus) was studied focusing on
      histochemical, ultrastructural, and morphometric characteristics of muscle
      fibers. Based on body length (cm), we studied four groups: G1=1.36+/-0.09,
      G2=3.38+/-0.44, G3=8.90+/-1.47, and G4=28.30+/-3.29 (mean+/-S.D.). All groups
      showed intense reaction to NADH-TR in subdermal fibers and weak or no reaction in
      deep layer fibers. In G3 and G4, an intermediate layer was also observed with
      fibers presenting weak reaction; in G4, groups of fibers with intense reaction
      were observed in the subdermal region. The myosin ATPase (m-ATPase) activities
      were acid-stable and alkali-labile in subdermal fibers; most deep layer fibers
      were alkali-stable and acid-labile. Intermediate fibers were acid-labile and
      alkali-stable. Two fiber populations were observed near deep muscle layer: one
      large presenting weak acid- and alkali-stable and the other small alkali-stable.
      During growth, muscle fiber hypertrophy was more evident in intermediate and
      white fibers for G3 and G4. However, in these groups, the presence of fiber
      diameters < or =21 microm suggested that there is still substantial fiber
      recruitment, confirmed by ultrastructural study, but hypertrophy is the main
      mechanism contributing to increase in muscular mass.

PMID- 12798128
TI  - The reaction of osteoclasts when releasing osteocytes from osteocytic lacunae in
      the bone during bone modeling.
AB  - Osteocytes are released from the osteocytic lacunae when osteoclasts resorb the
      bone matrix during bone modeling and remodeling. It remains unknown how
      osteoclasts react when releasing osteocytes during bone modeling, and the fate of
      these released osteocytes is also unclear. Femoral mid-shafts of 2-day-old
      kittens were sectioned into serial 0.5 microm-thick semithin or 0.1 microm-thick
      ultrathin sections, and examined by light microscopy (LM) and transmission
      electron microscopy (TEM). The sections showed many osteoclasts at the endosteum
      but there were no osteoblasts. There were many half-released, fully released,
      half-exposed, and fully exposed osteocytes on the bone surfaces. Many cell-like
      structures were seen in the cell bodies of osteoclasts by LM, and some semithin
      sections were re-sectioned into ultrathin sections for re-observation by TEM. By
      TEM, these were determinated to be mononuclear cells. The serial ultrathin
      sections showed that the mononuclear cells appeared to be engulfed in osteoclasts
      on one section but that the cell was connected with the bone surface of the
      osteocytic lacuna on another section. These results show that the mononuclear
      cells in the osteoclasts were osteocytes. The present study suggests that
      osteoclasts engulf some osteocytes but do not engulf others when releasing
      osteocytes during bone modeling.

PMID- 12798129
TI  - Leech responses to tissue transplantation.
AB  - The aim of the present work is to describe histologically, histochemically and
      immunocytochemically, the sequence of events that lead to first and second set
      rejection of allo- or xenograft in leeches. Graft responses of leeches are
      comparable and are described following specific steps: inflammatory phase,
      rejection phase and granulation tissue formation (including re-epithelialisation,
      angiogenesis and fibroplasia).The responses to first and second graft in first
      set graft rejection as well as to the first transplant in second set graft
      experiments are identical and in the time span of a week all grafts are destroyed
      and disappear. In the second set graft rejection experiments the responses
      against the second transplant are markedly accelerated. The second graft shows
      massive structural alterations and it is rapidly rejected, within 3-4 days.Our
      results permit to highlight that in leeches there is a specific responsiveness of
      immune system similar to those described in highly divergent phyla.

PMID- 12798130
TI  - Morphological and ultrastructural analysis of Turritopsis nutricula during life
      cycle reversal.
AB  - The hydrozoa life cycle is characterized, in normal conditions, by the
      alternation of a post-larval benthic polyp and an adult pelagic medusa; however,
      some species of Hydrozoa react to environmental stress by reverting their life
      cycle: i.e. an adult medusa goes back to the juvenile stage of polyp. This very
      uncommon life cycle could be considered as some sort of inverted metamorphosis. A
      morphological study of different stages during the reverted life cycle of
      Turritopsis nutricula led to the characterization of four different stages:
      healthy medusa, unhealthy medusa, four-leaf clover and cyst. The ultrastructural
      study of the cellular modifications (during the life cycle reversion of T.
      nutricula) showed the presence of both degenerative and apoptotic processes.
      Degeneration was prevalent during the unhealthy medusa and four-leaf clover
      stages, while the apoptotic rate was higher during the healthy medusa and cyst
      stages. The significant presence of degenerative and apoptotic processes could be
      related to the occurrence of a sort of metamorphosis when an adult medusa
      transforms itself into a polyp.

PMID- 12798131
TI  - Evaluation of rat thyroid gland morphophysiological status after three months
      exposure to 50 Hz electromagnetic field.
AB  - Objective of our study was to use morphophysiological criteria in order to
      determine the sensitivity of male rat thyroid gland to an extremely low frequency
      electromagnetic field (ELF-EMF) influence and the ability of the gland to repair
      after period of exposure. Animals were exposed to 50Hz, 50-500 microT ELF-EMF for
      3 months when a part of them (group I) were sacrificed, while the rest of animals
      were subjected to recovery evaluation of the gland and sacrificed after 1 (group
      II), 2 (group III) and 3 (group IV) weeks. Histological and stereological
      analyses were performed on paraffin and semifine thyroid gland sections. Serum T3
      and T4 were also determined. Histological and stereological analyses showed that
      the volume density of follicular epithelium and thyroid activation index
      decreased, while the volume density of colloid and capillary network increased in
      group I, II and III. The values of all these parameters in group IV were similar
      to corresponding controls. Serum T3 and T4 concentrations were significantly
      lower in all exposed animals, except in group I. Results of this study
      demonstrate that after significant morphophysiological changes caused by ELF-EMF
      exposure thyroid gland recovered morphologically, but not physiologically, during
      the investigated repair period.

PMID- 12798132
TI  - Epithelial polarity and morphogenesis.

PMID- 12798133
TI  - SNAREs and epithelial cells.
AB  - SNARE proteins control the membrane fusion events of membrane trafficking
      pathways. Work in epithelial cells has shown that polarized trafficking to the
      apical and basolateral plasma membrane domains requires different sets of SNAREs,
      suggesting a mechanism that contributes to the overall specificity of polarized
      trafficking and, perhaps, the formation and maintenance of polarity itself. This
      article describes methods that have been designed and adapted specifically for
      the investigation of SNAREs in epithelial cells. The knowledge of the subcellular
      localization of a SNARE of interest is essential to understand its function.
      Unfortunately, the endogenous expression levels of SNAREs are often low which
      makes detection challenging. We provide guidelines for determination of the
      localization of SNAREs by immunofluorescence microscopy including methods for
      signal amplification, antigen retrieval, and suppression of antibody cross
      reactivity. To define which trafficking pathway a SNARE of interest is involved
      in, one needs to specifically inhibit its function. We provide guidelines for
      SNARE inhibition by overexpression of the SNARE of interest. An alternative is to
      introduce inhibitors of SNARE function, such as antibodies or clostridial toxins,
      into cells. Two methods are presented to make this possible. The first allows the
      monitoring of effects on trafficking pathways by biochemical assays, and is based
      on plasma membrane permeabilization using the bacterial toxin streptolysin-O. The
      second is suitable for single-cell observations and is based on microinjection.

PMID- 12798134
TI  - Ultracentrifugation-based approaches to study regulation of Sec6/8 (exocyst)
      complex function during development of epithelial cell polarity.
AB  - The Sec6/8 (exocyst) complex is an essential component of the exocytic apparatus
      and plays an evolutionarily conserved role in polarized membrane growth. During
      development of epithelial cell polarity, this cytosolic protein complex is
      recruited to plasma membrane sites of cell-cell contact, where it facilitates
      exocytosis to the lateral membrane domain. However, the identity of membrane
      binding sites for Sec6/8 complex, mechanisms regulating association of Sec6/8
      complex with these sites, and the precise function of the complex in polarized
      trafficking are not known. Biochemical strategies involving differential, rate
      zonal, and isopycnic density gradient ultracentrifugation are providing clues to
      these questions.

PMID- 12798135
TI  - Analysis of hydrostatic pressure-induced changes in umbrella cell surface area.
AB  - All cells experience and respond to external mechanical stimuli including shear
      stress, compression, and hydrostatic pressure. Cellular responses can include
      changes in exocytic and endocytic traffic. An excellent system to study how
      extracellular forces govern membrane trafficking events is the bladder umbrella
      cell, which lines the inner surface of the mammalian urinary bladder. It is
      hypothesized that umbrella cells modulate their apical plasma membrane surface
      area in response to hydrostatic pressure. Understanding the mechanics of this
      process is hampered by the lack of a suitable model system. We describe a
      pressure chamber that allows one to increase hydrostatic pressure in a
      physiological manner while using capacitance to monitor real-time changes in the
      apical surface area of the umbrella cell. It is demonstrated that application of
      hydrostatic pressure results in an increase in umbrella cell apical surface area
      and a change in the morphology of umbrella cells from roughly cuboidal to
      squamous. This process is dependent on increases in cytoplasmic Ca(2+). This
      system will be useful in further dissecting the mechanotransduction pathways
      involved in cell shape change and regulation of exocytic and endocytic traffic in
      umbrella cells.

PMID- 12798136
TI  - Testing effects of signal transduction pathways on cadherin junctional complex
      assembly using quantitative image analysis.
AB  - Cadherin adhesion molecules function in numerous cell biological processes that
      influence embryo development, normal cell physiology, and pathophysiology of many
      disease processes. Cadherins nucleate the assembly of the adherens junction, a
      cell-to-cell adhesion plaque that is prominent in simple epithelial cells and
      found in many cell types. Numerous cell biological approaches have been used to
      study this interesting class of molecules. Here, we outline methodology used in
      our studies of junctional complexes to examine effects of signaling molecules on
      assembly mechanisms. This is a quantitative method that allows the investigator
      to test the combined effect of two different signaling processes to determine
      whether these two signals act in concert within the same pathway. We discuss how
      this method could be generalized to other studies to examine consequences of
      various experimental manipulations on the assembly of cellular structures.

PMID- 12798137
TI  - Functional analysis of tight junctions.
AB  - Epithelial and endothelial cells are joined to each other via a set of
      intercellular junctions that differ in their morphological appearance,
      composition, and function. The tight junction or zonula occludens is the
      intercellular junction that regulates diffusion between cells and therefore
      allows endothelia and epithelia to form cellular barriers that separate
      compartments of different composition. This intercellular gate formed by tight
      junctions is not only highly regulated but is size- and ion-selective and, hence,
      represents a semipermeable diffusion barrier. In epithelia, tight junctions form
      a morphological and functional border between the apical and basolateral cell
      surface domains. They directly contribute to the maintenance of cell surface
      polarity by forming a fence that prevents apical/basolateral diffusion of lipids
      in the outer leaflet of the plasma membrane. Here we describe a set of assays
      that allow the analysis of tight junctions to determine their integrity and
      functional state.

PMID- 12798138
TI  - Integrins in epithelial cell polarity: using antibodies to analyze adhesive
      function and morphogenesis.
AB  - Epithelial cells polarize in response to cell-substratum and cell-cell adhesive
      interactions. Contacts between cells and proteins of the extracellular matrix are
      mediated by integrin receptors. Of the 24 recognized integrin heterodimers,
      epithelial cells typically express four or more distinct integrins, with the
      exact complement dependent on the tissue of origin. Investigation of the roles of
      integrins in epithelial cell polarization has depended on the use of function
      blocking antibodies both to determine ligand specificity of individual integrins
      and to disrupt and redirect normal morphogenesis. In this article we describe
      techniques for employing function-blocking anti-integrin antibodies in adhesion
      assays of the polarized Madin-Darby canine kidney (MDCK) cell line and to
      demonstrate the involvement of beta1 integrins in collagen-induced tubulocyst
      formation. These techniques can be easily expanded to other antibodies and
      epithelial cell lines to characterize specific functions of individual integrins
      in epithelial morphogenesis.

PMID- 12798140
TI  - Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three
      dimensional basement membrane cultures.
AB  - The three-dimensional culture of MCF-10A mammary epithelial cells on a
      reconstituted basement membrane results in formation of polarized, growth
      arrested acini-like spheroids that recapitulate several aspects of glandular
      architecture in vivo. Oncogenes introduced into MCF-10A cells disrupt this
      morphogenetic process, and elicit distinct morphological phenotypes. Recent
      studies analyzing the mechanistic basis for phenotypic heterogeneity observed
      among different oncogenes (e.g., ErbB2, cyclin D1) have illustrated the utility
      of this three-dimensional culture system in modeling the biological activities of
      cancer genes, particularly with regard to their ability to disrupt epithelial
      architecture during the early aspects of carcinoma formation. Here we provide a
      collection of protocols to culture MCF-10A cells, to establish stable pools
      expressing a gene of interest via retroviral infection, as well as to grow and
      analyze MCF-10A cells in three-dimensional basement membrane culture.

PMID- 12798141
TI  - Apical surface formation in MDCK cells: regulation by the serine/threonine kinase
      EMK1.
AB  - It has recently become evident that basic mechanisms for the establishment of
      cell polarity are conserved between epithelial and nonepithelial systems. The
      vast catalogue of known gene products involved in various aspects of invertebrate
      and yeast cell polarity provides a repertoire of candidate proteins that can be
      tested for their roles in the organization of mammalian epithelia. Here, we
      describe cell biological approaches to study the development and maintenance of
      cell polarity in Mardin-Darby canine kidney (MDCK) cells, an established
      mammalian model cell line for simple epithelia. The assays allowed us to
      characterize the Caenorhabditis elegans PAR-1 homologue EMK1 as a novel regulator
      of apical surface formation in epithelial cells.

PMID- 12798142
TI  - In vivo gene transfer as a means to study the physiology and morphogenesis of the
      retinal pigment epithelium in the rat.
AB  - Our understanding of the morphogenesis of epithelial phenotypes has been greatly
      advanced by the use of in vitro cell culture systems. However, cell cultures
      often do not faithfully reconstitute many of the differentiated properties of the
      cell from which they are derived and cannot be used to examine complex
      physiologic interactions between adjacent tissues. This is particularly true of
      the retinal pigment epithelium (RPE). Many plasma membrane proteins, in vivo,
      exhibit a reversed polarity with respect to other epithelia, and RPE-derived cell
      lines seldom exhibit these same polarity properties. Furthermore, the interaction
      between the RPE cell and the neuorsensory retina, or the underlying blood supply,
      the choroid, is absent in cell culture. Most epithelia are difficult to isolate
      and study in vivo. The RPE is an exception to this. We have explored several
      aspects of RPE protein transport properties, vision-related physiology, and
      disease-related pathophysiology in the eye using in vivo gene transfer and
      electrophysiologic techniques. By injecting replication-defective adenoviruses
      into the subretinal space of rat eyes, we have been able to easily direct the
      expression of a test protein and follow its sorting and physiologic effects on
      RPE cells and adjacent tissues. Due to binding and internalization of adenoviral
      vectors to integrins found on the RPE apical plasma membrane, expression in a
      healthy eye is essentially confined to the RPE cell, even under control of a
      cytomegalovirus promotor. The use of varying amounts of adenoviral vector allows
      for determination of dose-responsive effects and the comparison of multiple
      mutants of a protein. In addition, there are substantial savings with respect to
      time and money in comparison to standard transgenic approaches.

PMID- 12798139
TI  - To create the correct microenvironment: three-dimensional heterotypic collagen
      assays for human breast epithelial morphogenesis and neoplasia.
AB  - The normal human breast comprises an inner layer of luminal epithelial cells and
      an outer layer of myoepithelial cells separated from the connective tissue stroma
      by an intact basement membrane. In breast cancer, tumor cells are in direct
      contact with the surrounding highly activated collagenous stroma, with little or
      no discernible myoepithelial fence from the original double-layered structure. To
      understand the evolution of these two scenarios, we took advantage of a three
      dimensional hydrated collagen gel approach. The contribution of myoepithelial
      cells to normal morphogenesis was studied by ablation and rescue experiments, and
      genes regulated on tumor cell-fibroblast interaction were identified in a tumor
      environment assay. In normal breast morphogenesis, the ability to correctly
      polarize sialomucin to the luminal membrane of emerging acini was used as a
      criterion for apical polarity and functional differentiation. In the assay of
      breast neoplasia, the consequence of reciprocal tumor cell-fibroblast interaction
      was addressed morphologically as well as by a differential display approach.
      Normal breast epithelial cells were purified immunomagnetically and an
      established cell line, MCF-7, was used as a surrogate tumor cell. With regard to
      the importance of myoepithelial cells in normal breast epithelial morphogenesis,
      the collagen gel assay elucidated the following subtleties: In contrast to
      culturing in basement membrane gels, luminal epithelial cells when cultured alone
      made structures that were all inversely polarized. This aberrant polarity could
      be rescued by co-culture with myoepithelial cells. The molecular activity of
      myoepithelial cells responsible for correct morphogenesis was narrowed down to
      the laminin-1 component of the basement membrane. As for the consequence of
      interaction of tumor cells with connective tissue fibroblasts, the assay allowed
      us to identify a hitherto undescribed gene referred to as EPSTI1. The relevance
      of the assay-based identification of regulated genes was confirmed in a series of
      breast carcinomas in which EPSTI1 was highly upregulated compared with normal
      breast. Few if any of these observations would have been possible on two
      dimensional tissue culture plastic.

PMID- 12798143
TI  - Hermite acuity gratings and models of space-variant acuity.
AB  - A coherent mathematical framework for the psychophysics of contrast perception
      emerges when contrast sensitivity is posed as an eigenvalue problem. This more
      general mathematical theory is broad enough to encompass Fourier analysis as it
      is used in vision research. We present a model of space-variant contrast
      detection to illustrate the main features of the theory, and obtain a new
      contrast sensitivity function using acuity gratings based on the Hermite
      functions. The Hermite gratings have several advantages: they represent a
      complete orthogonal basis, are easy to manipulate, and are of finite extent. A
      theoretical Hermite csf results from posing contrast perception as an eigenvalue
      problem. Surprisingly, the theoretical Hermite csf is determined by a single
      empirical parameter.

PMID- 12798144
TI  - The spatial tuning of chromatic adaptation.
AB  - A key question in colour research is how the colour and spatial analysis of an
      image interact. Traditionally, colour and form analysis have been regarded as
      parallel and separate processes, and documented effects of image complexity on
      chromatic adaptation have been attributed to a temporal integration process
      during eye movements. Evidence is presented here for a spatial mechanism, which
      tunes chromatic adaptation to the luminance structure (spatial frequency and
      orientation) of an image. This in turn suggests a close cooperation between
      colour and form analysis during chromatic adaptation. The results are discussed
      in relation to the "segregated pathway hypothesis" and the role of spatial
      aspects for the computation of colour constancy and adaptation to natural scenes.

PMID- 12798145
TI  - Perceived onset time and position of a moving stimulus.
AB  - During the few past years, there has been a growing interest in the timing and
      locating of moving stimuli. The most popular spatio-temporal phenomena that have
      been studied are the flash-lag effect (FLE) [Nature 370 (1994) 256] and the
      Frohlich effect (FE) [Z. Sinnesphysiol. 54 (1923) 58]. Most often these phenomena
      are examined by some spatial task (e.g., judging whether moving and flashed
      stimuli are spatially aligned or not; explicitly pointing or adjusting the moving
      stimulus position). Usually, from the measured spatial offset temporal
      differences in processing of moving and stationary stimuli are inferred. Our
      experiments show that this practice may not be justified because the spatial and
      temporal properties were clearly disassociated for the movement onset perception.
      The disassociation demonstrates that the FLE and FE are most probably based on
      different internal representations.

PMID- 12798146
TI  - Localization of shapes: eye movements and perception compared.
AB  - The localization of spatially extended objects is thought to be based on the
      computation of a default reference position, such as the center of gravity. This
      position can serve as the goal point for a saccade, a locus for fixation, or the
      reference for perceptual localization. We compared perceptual and saccadic
      localization for non-convex shapes where the center of gravity (COG) was located
      outside the boundary of the shape and did not coincide with any prominent
      perceptual features. The landing positions of single saccades made to the shape,
      as well as the preferred loci for fixation, were near the center of gravity,
      although local features such as part boundaries were influential. Perceptual
      alignment positions were also close to the center of gravity, but showed
      configural effects that did not influence either saccades or fixation. Saccades
      made in a more naturalistic sequential scanning task landed near the center of
      gravity with a considerably higher degree of accuracy (mean error <4% of saccade
      size) and showed no effects of local features, constituent parts, or stimulus
      configuration. We conclude that perceptual and oculomotor localization is based
      on the computation of a precise central reference position, which coincides with
      the center of gravity in sequential scanning. The saliency of the center of
      gravity, relative to other prominent visual features, can depend on the specific
      localization task or the relative configuration of elements. Sequential scanning,
      the more natural of the saccadic tasks, may provide a better way to evaluate the
      "default" reference position for localization. The fact that the reference
      position used in both oculomotor and perceptual tasks fell outside the boundary
      of the shapes supports the importance of spatial pooling, in contrast to local
      features, in object localization.

PMID- 12798147
TI  - Visual comparisons within and between object parts: evidence for a single-part
      superiority effect.
AB  - Subjects judged whether two marks placed at different positions along a curved
      contour were physically the same. When targets were separated by a concave
      curvature extremum--corresponding to a part-boundary--decision latencies were
      longer than when they straddled an equally curved convex extremum, demonstrating
      a "single-part superiority effect". This difference increased with both stimulus
      duration and the magnitude of contour curvature. However, it disappeared when the
      global configuration was not consistent with a part-boundary interpretation,
      suggesting a critical role of global organization in part decomposition.

PMID- 12798148
TI  - Spatial localization precedes temporal determination in visual perception.
AB  - The temporal order of two spots of light successively appearing in the dark, just
      before a saccade, influences their perceived spatial relation. Both spots are
      mislocalized in the saccade direction--the second more so than the first--because
      mislocalization grows as time elapses from stimulus to saccade onset. On the
      other hand, the perceived order of the two spots may be altered if the second
      spot is at the focus of spatial attention. How would these illusory perceptions
      of space and time interact when they are brought to play together? Could they be
      independent or could one perception depend on the other? Here we show that
      perceived location of stimuli is not affected by illusory temporal order, whereas
      perceived temporal order is affected by misperceived location. The results
      suggest that the brain processes spatial location of visual stimuli before
      processing their temporal order.

PMID- 12798150
TI  - Simultaneously recording local luminance responses, spatial and temporal
      interactions in the visual system with m-sequences.
AB  - In this paper, an extended multifocal VEP/ERG paradigm, referred to as the
      unified multifocal electroretinography and visual evoked potential paradigm
      (UMEV), is presented. This paradigm allows a simultaneous recording of luminance
      responses, temporal interactions, spatial interactions and spatial-temporal
      interactions. Two studies were conducted to demonstrate the capability and
      validity of the UMEV. The results show that the UMEV system derives a significant
      spatial interaction VEP in addition to a similar luminance response (mfERG) and
      pattern reversal VEP (mfVEP) to the VERIS system. Second, the amplitude of
      spatial interaction VEP is diminished by increasing the distance between two
      stimuli while the amplitude of temporal interaction VEP remain relatively
      unchanged.

PMID- 12798149
TI  - Unilateral posterior parietal lobe lesions affect representation of visual space.
AB  - This study assessed accuracy of visually perceived vertical and trunk median
      plane orientation in 41 subjects: 17 had unilateral brain lesions including the
      posterior parietal lobe (PPL), 8 had lesions outside PPL, and 16 were
      neurologically normal. Vertical perception errors clearly increased with size of
      unilateral lesions to PPL and posterior superior temporal gyrus (PSTG). Median
      plane perception errors increased only slightly with size of unilateral lesions
      to frontal lobe premotor areas and supramarginal gyrus. These results are
      compatible with the hypothesis that accurate visual vertical perception depends
      critically on intact PPL and PSTG in both cerebral hemispheres while accurate
      median plane perception likely involves a bihemispheric network that can
      compensate for lesions to one hemisphere.

PMID- 12798151
TI  - Streptococcal diversity in oral biofilms with respect to salivary function.
AB  - OBJECTIVE: In a previous study, we screened 149 subjects and established four
      groups high or low for salivary killing of oral bacteria, and for aggregation and
      live and dead adherence of oral bacteria (as a combined factor). Caries scores
      were significantly lower in both High Aggregation-Adherence groups. In this study
      we looked at the effects of those differences in salivary function on the
      quantity and diversity of oral biofilm streptococci. DESIGN: Subjects from those
      four groups were recalled for collection of overnight oral biofilm from buccal
      upper central incisors, lingual lower central incisors, buccal upper and lower
      first molars, and lingual upper and lower first molars. At each site, groups were
      compared for total biofilm (by DNA concentration), total streptococci (by
      quantitative PCR), and streptococcal diversity (by Streptococcus-specific
      denaturing gradient gel electrophoresis). RESULTS: Total biofilm DNA and total
      streptococci were correlated. Both were highest on buccal molar surfaces and
      lowest on lingual lower central incisors, and both were significantly lower in
      the High Aggregation-Adherence groups (particularly at the buccal molar site).
      Fifty distinct bands were observed in denaturing gradient gels. There was great
      diversity within and between sites. Three major bands were present in almost
      every person at every site. Densities for two of those bands were significantly
      lower in both High Aggregation-Adherence groups. Other less-prevalent bands also
      showed the same pattern. CONCLUSION: These findings are consistent with our
      caries results in suggesting that differences in salivary function can influence
      the quantity and composition of streptococci in oral biofilms.

PMID- 12798152
TI  - PCR-based identification of Treponema maltophilum, T amylovorum, T medium, and T
      lecithinolyticum in primary root canal infections.
AB  - OBJECTIVE: Molecular genetic methods have significantly contributed to the
      knowledge about the microbiota associated with infected root canals. Albeit
      spirochetes have been commonly observed in primary root canal infections, only
      recently they have been identified. The purpose of the present study was to
      investigate the occurrence of four treponemes-Treponema maltophilum, Treponema
      lecithinolyticum, Treponema amylovorum, and Treponema medium-in cases of primary
      endodontic infections associated with different forms of periradicular diseases
      through a 16S rDNA-based nested PCR assay. DESIGN: Samples were taken from thirty
      one infected root canals associated with either asymptomatic or symptomatic
      apical periodontitis. DNA extracted from the samples was initially amplified
      using universal 16S rDNA primers, followed by a second round of amplification
      using the first PCR products to detect a specific fragment of the 16S rDNA of
      each target Treponema species. RESULTS: All cases were positive for the universal
      bacterial primers, indicating that samples contained bacterial DNA. Of the four
      target species, T. maltophilum was the most prevalent, being detected in 39% of
      the cases (33% of the asymptomatic cases and 50% of the symptomatic cases). T.
      lecithinolyticum was the next more prevalent among the species tested, being
      found in 26% of the samples (33% of asymptomatic cases and 10% of the symptomatic
      cases). T. amylovorum was found in 7% of the cases (5% of the asymptomatic cases
      and 10% of the symptomatic cases), while T. medium was in 13% of the cases (14%
      of the asymptomatic cases and 10% of the symptomatic cases). None of the species
      tested was significantly associated with clinical symptoms. CONCLUSIONS: This was
      possibly the hitherto first study to report the occurrence of T.
      lecithinolyticum, T. amylovorum, and T. medium in infections of endodontic
      origin. Overall, findings suggested that these oral treponemes, particularly T.
      maltophilum and T. lecithinolyticum, can be involved in the pathogenesis of
      periradicular diseases.

PMID- 12798153
TI  - Efficacy of differently concentrated chlorhexidine varnishes in decreasing Mutans
      streptococci and lactobacilli counts.
AB  - The objective of the present prospective trial was to compare the efficacy of
      differently concentrated chlorhexidine varnishes (EC40) = 40% chlorhexidine and
      Cervitec = 1% chlorhexidine + 0.1% thymol) on levels of Mutans streptococci (ms),
      lactobacilli (lb) and plaque formation in interproximal plaque and saliva. Twenty
      four volunteers with a high level of ms in saliva were randomized into two groups
      and treated with the experimental varnishes. Varnish applications were performed
      in accordance with literature. Over a period of 2 weeks Cervitec was applied
      three times and EC40 once or twice, depending on ms counts after first
      application. Four and 12 weeks after final varnish application ms in plaque and
      saliva were evaluated. Furthermore, lactobacilli (lb) counts in saliva and the
      effect on plaque formation were recorded. Both varnishes revealed a reduction of
      ms in interproximal plaque and saliva after 4 and 12 weeks. The highly
      concentrated varnish revealed a significantly stronger reduction of ms in plaque
      and saliva compared with the lowly-concentrated varnish. No effect could be
      demonstrated on lb counts and plaque formation. The results indicate that the
      chlorhexidine varnishes tested may reduce ms in both interproximal plaque and
      saliva. However, the application of the highly concentrated varnish EC40 results
      in a higher decrease of ms in plaque sites and saliva.

PMID- 12798154
TI  - Minor gland and whole saliva in postmenopausal women using a low potency
      oestrogen (oestriol).
AB  - Many women undergo hormone replacement therapy in order to relieve menopausal and
      postmenopausal symptoms. Oral discomfort is common among these symptoms and
      studies have shown that the stimulated whole saliva flow rate is increased after
      combined oestradiol and progesterone replacement therapy. There is, however, no
      data regarding the effect of other oestrogens or of oestrogen alone on whole and
      minor gland saliva. In the present study, the flow rate from minor salivary
      glands (buccal, labial and palatal) and the secretion rate and buffer capacity of
      whole saliva was examined in 18 postmenopausal women (61-76 years) prior to, and
      during 1 year of a low potency oestrogen (oestriol) use. The ability of whole
      saliva to aggregate and mediate bacterial adherence as well as subjective
      feelings of dry mouth was also examined. For comparison, the same variables were
      examined in nine peri- and postmenopausal, non-medicated women (reference group,
      53-61 years). During hormone treatment, the labial saliva flow was significantly
      increased and the complaints of dry mouth reduced. Increased stimulated whole
      saliva flow was seen in both the hormone and reference groups. This was also true
      for the stimulated whole saliva buffer capacity, which was increased parallel to
      the flow rate. The secretion rates were generally lower in the hormone group
      compared to the reference group throughout the study period. Except for
      stimulated whole saliva, statistical analysis at baseline revealed no age-related
      reduction of the saliva flow rates. The ability of whole saliva to mediate
      aggregation of Actinomyces naeslundii was significantly decreased after hormone
      treatment. Thus, the present findings indicate that a low dose oestrogen
      (oestriol) may affect the flow rate of labial salivary glands and the bacterial
      aggregation activity of whole saliva.

PMID- 12798155
TI  - Cbfa1/Runx2 gene expression in articular chondrocytes of the mice
      temporomandibular and knee joints in vivo.
AB  - Healthy articular cartilage is thought to be maintained by the modulation of
      Cbfa1 expression, although little is currently known about Cbfa1 expression in
      such tissues. Therefore, we examined in vivo Cbfa1 transcript levels in the
      temporomandibular (TM) and knee joints of 3- and 10-week-old male ICR mice
      (weighing 50-70 g). A digoxigenin-11-UTP-labeled single-stranded RNA probe (0.6
      kbp PstI-HindIII fragment of the 3' of untranslated region in exon 8 of mouse
      Cbfa1 cDNA) was prepared and in situ hybridization was performed on paraffin
      embedded TM and knee joint sections. The antisense probe detected Cbfa1
      transcripts in prehypertrophic chondrocytes, but not in the articular surface
      layer chondrocytes of 3- and 10-week-old mice TMJs. Despite the intense Cbfa1
      expression in prehypertrophic chondrocytes, articular surface layer chondrocytes
      of the knee joints expressed low and undetectable level of Cbfa1 in the 3- and 10
      week-old mice, respectively. These results indicate that Cbfa1 are highly
      expressed in the prehypertrophic chondrocytes presumably for articular tissue
      remodeling during the entire lifespan of the mouse, whereas Cbfa1 expression is
      suppressed in the articular surface chondrocytes in the adult mouse TM and knee
      joints to obtain the permanent cartilage phenotype.

PMID- 12798156
TI  - Dentin deformation after scratching with clinically-relevant forces.
AB  - OBJECTIVE: In order to understand the mechanism of dentin sensitivity to tactile
      stimuli, the purpose of this study was to evaluate possible permanent deformation
      of dentin produced by scratching dentin surfaces with clinically-relevant forces.
      METHODS: Midcoronal dentin was prepared from twenty human teeth and polished to
      4000-grit and ultrasonicated. The dentin surface of each specimen was scratched
      under forces ranging from 30 to 100 centi-Newtons (cN). The depth of the grooves
      were measured with a profilometer and the overall hardness of dentin in the
      vicinity of the grooves was measured. Additional dentin specimens were prepared
      for SEM evaluation. RESULTS: Dentin hardness was constant and no statistical
      difference was found among the specimens. Statistically significant differences
      in groove width and depth were found when increasing force was applied to the
      dental explorer tip. The depth of the groove ranged from 0.21+/-0.09 microm for
      the 30 cN group to 1.27+/-0.39 microm for the 100 cN group. The width of the
      groove ranged from 19.3+/-4.0 microm for the 30 cN group to 43.0 microm for the
      10 0 cN group. CONCLUSIONS: (1). The threshold force necessary to create
      scratches in dentin with a dental explorer was 30 cN or a compressive stress of
      1003 MPa. As this exceeds the crushing strength of dentin, this force produces
      plastic deformation of dentin; (2). Theoretical calculations indicated that even
      the highest scratching forces (100 cN) could not induce sufficient fluid flow to
      activate pulpal mechanoreceptors, although it could induce sufficient elastic
      deformation to theoretically shift dentinal fluid at a rate sufficient to
      activate mechanoreceptors; (3). The results of this work may lend support the
      hydrodynamic theory in that scratching of dentin surfaces causes both elastic and
      plastic deformation of dentin that may displace dentinal fluid toward the pulp
      where it could activate mechanoreceptors.

PMID- 12798157
TI  - Minor salivary gland secretion in children and adults.
AB  - The minor salivary glands are of great importance in the physiology and pathology
      of the oral cavity. So far, studies of the minor glands have concentrated on
      adults. In the present study, minor salivary gland secretion was studied in the
      buccal and labial mucosa of 3-year-old children, adolescents and young adults. In
      addition, the number of glands per surface area was assessed in the labial
      mucosa. A total of 90 individuals were included, 30 in each age-group. Saliva was
      collected on filter paper discs and the salivary secretion rate was measured
      using a Periotron 8000. The number of secreting labial glands was assessed on PAS
      stained filter paper discs under a microscope. Salivary secretion in the buccal
      mucosa was found to be age-related, with a statistically significant lower rate
      of secretion (P=0.003) in the 3-year-olds (mean 7.7 microl x cm(-2) x min(-1))
      compared with the young adults (11.9 microl x cm(-2) x min(-1)). No significant
      differences between the sexes were noted. For the labial glands, no age- or sex
      related differences were found. In all age-groups, salivary secretion was
      significantly higher in the buccal than in the labial mucosal area. A
      statistically significant difference in number of secreting glands was found
      between all age-groups, with a decreasing number of glands per surface unit with
      age. The number of glands was significantly lower in males compared with females
      in the group of adults. The lower rate of buccal salivary secretion in the young
      children may imply that the oral mucosa is more vulnerable to external injury and
      that caries protection on the buccal molar surfaces is lower. Previous studies
      indicate that adults with a reduced rate of minor salivary gland secretion are
      more susceptible to caries.

PMID- 12798158
TI  - Neuropeptide expression following ligation of the ferret lingual nerve.
AB  - Previous studies on the ferret inferior alveolar nerve found a close association
      between the spontaneous neural activity generated at a site of nerve injury, and
      the accumulation of neuropeptides in the injured axons. More recent
      electrophysiological studies on the lingual nerve revealed high levels of
      spontaneous activity 3 days after injury, a decline at 3 weeks and a late rise at
      3 months. In the present study we have used immunocytochemical techniques to see
      whether this time course of spontaneous activity is again paralleled by an
      accumulation of neuropeptides. In 20 anaesthetised adult ferrets the left lingual
      nerve was ligated and sectioned distally, and the animals left to recover for 3
      days, 3 weeks or 3 months. The tissue was processed using indirect
      immunofluorescence and image analysis was used to quantify levels of the
      neuropeptides; calcitonin gene-related peptide (CGRP), substance P (SP),
      vasoactive intestinal polypeptide (VIP), galanin (GAL), enkephalin (ENK) and
      neuropeptide Y (NPY). Immunoreactivity to all of the neuropeptides was present
      proximal to the ligature 3 days after injury, and these high levels of expression
      had decreased considerably by 3 weeks. By 3 months ENK and NPY expression had
      almost disappeared proximal to the ligature, but levels of CGRP, SP, VIP and GAL
      had increased slightly. This was also accompanied by an accumulation of all of
      the neuropeptides, except NPY, in the portion of nerve immediately distal to the
      ligature. This late accumulation of certain neuropeptides coincides with the
      increase in spontaneous activity seen in our previous electrophysiological
      studies and supports the suggestion that neuropeptides may play a role in the
      aetiology of sensory disorders after nerve injury.

PMID- 12798159
TI  - Phenylisothiocyanate and dansyl chloride precolumn derivatizations for the high
      performance liquid chromatography analysis of the antitumoral agent ES-285 in dog
      plasma.
AB  - Chromophor and fluorophor addition reactions involving phenylisothiocyanate
      (PITC) and dansyl chloride (DC) were optimized to adapt two high-performance
      liquid chromatography (HPLC) procedures designed for the accurate determination
      of the novel antitumoral agent ES-285 in Beagle dog plasma. ES-285 was reacted
      with PITC at 60 degrees C for 15 min in the presence of triethylamine. The dansyl
      derivative was obtained by reaction of ES-285 with dansyl chloride in a basic
      medium at 80 degrees C for 20 min. Both reactions also worked for ES-299, a
      compound structurally related to ES-285 which was used as internal standard. The
      treatment of ES-285 and ES-299 spiked plasma samples with a basic phosphate
      buffer and MeOH permitted the extraction of the drug from the matrix. The
      purification of the analytes was carried out by solid-phase extraction followed
      by precolumn derivatization with PITC and DC. The phenylisothiocyanate adducts
      were analyzed by isocratic HPLC with UV detection at 254 nm. The ES-285 and ES
      299 derivatives were eluted from a C(18) column at approximately 6.9 and
      approximately 8.1 min, respectively. The eluent ACN-water (95:5, v/v) was
      delivered to the column at a flow-rate of 1 ml/min and the analysis was completed
      in 15 min. The dansyl derivatives were analysed by a two-HPLC column system with
      fluorescence detection and gradient elution. The column temperature was
      maintained at 40 degrees C. The analysis lasted 55 min with the elution of ES-285
      and ES-299 derivatives at approximately 35.2 and approximately 37.9 min,
      respectively. The PITC- and DC-based procedures were characterized by limits of
      quantification of 20 and 15 ng/ml, respectively. Both procedures were validated
      according to the ICH and FDA guidelines. They were selective for ES-285 and
      provided accurate, precise and reproducible results. ES-299 was shown to be a
      suitable internal standard. The HPLC procedure involving derivatization with DC
      was more sensitive and permitted to process plasma sample volumes as low as 100
      microl. On the other hand, the PITC-based procedure characterised by a quite
      similar LOQ permitted a higher throughput but implied the processing of a 500
      microl plasma volume.

PMID- 12798160
TI  - Kinetic differentiation mode chromatography using 8-quinolinol and fluorimetric
      detection for sensitive determination of aluminum adhering to the gastric mucosa.
AB  - A highly sensitive method of kinetic differentiation (KD) mode high-performance
      liquid chromatography (HPLC) with fluorimetric detection was established using 8
      quinolinol to measure aluminum adhering to the gastric mucosa. After sucralfate
      was hydrolyzed by 1 mol/l hydrochloric acid, an 8-quinolinolate-aluminum complex
      was produced by reacting aluminum with an 8-quinolinol solution. Then
      contaminants in the gastric mucosa and sucralfate were removed by liquid-liquid
      extraction with chloroform. Next, the 8-quinolinolate-aluminum complex was
      separated on a reversed-phase column that was specifically designed to detect
      aluminum (50 x 4.6-mm I.D.). Separation was done at a flow-rate of 0.8 ml/min,
      using BES buffer containing sodium dodecyl sulfate (pH 7.0) as the mobile phase.
      Fluorescence was detected at 370 nm (excitation) and 504 nm (emission). The
      sensitivity of this method was more than 1000 times greater than that of
      absorptiometry using 8-quinolinol. The detection and quantitation limits were
      1.68 and 5.11 ng/ml, respectively. When tested with aluminum solutions of 10, 30,
      and 90 ng/ml, the intra-assay and inter-assay coefficients of variation were
      below 7.1%, with an error of less than 8.3%. Aluminum adhering to the gastric
      mucosa was determined by HPLC and absorptiometry after administration of
      sucralfate to rats. The HPLC method showed that aluminum levels were higher at
      sites of ulceration than in the normal mucosa at all times after sucralfate
      administration. When the values above zero obtained for absorptiometry were
      assessed, there was a significant correlation (r=0.993, P<0.0001) between the
      aluminum concentrations measured by the two methods. This new HPLC method could
      be applied to the determination of aluminum in small samples, such as human
      gastric mucosal biopsy specimens.

PMID- 12798161
TI  - Analysis of pentacyclic triterpenic acids from frankincense gum resins and
      related phytopharmaceuticals by high-performance liquid chromatography.
      Identification of lupeolic acid, a novel pentacyclic triterpene.
AB  - An HPLC gradient method with photodiode array detection was developed for the
      simultaneous analysis of 12 different pentacyclic triterpenic acids in Indian and
      African frankincense gum resins as well as in related phytopharmaceuticals. The
      triterpenic acids were obtained by an exhaustive extraction procedure.
      Identification of the compounds was based on retention times, UV-spectra and add
      on technique with standards isolated from African frankincense. The method allows
      differentiation of frankincense of different origin and standardization of
      frankincense-based phytopharmaceuticals. Further, this is the first report
      identifying a novel pentacyclic triterpene, lupeolic acid, as a constituent of
      frankincense gum resins.

PMID- 12798162
TI  - Determination of chloramphenicol residues in shrimps by liquid chromatography
      mass spectrometry.
AB  - A liquid chromatographic method with mass spectrometric detection and
      identification (LC-MS) is presented for the determination of chloramphenicol
      (CAP) in shrimp tissues. Homogenized shrimp samples were extracted with phosphate
      buffer (pH 7.0). Clean-up was carried out on a C(18) SPE cartridge.
      Chloramphenicol was determined by LC-MS-ESI in negative mode. The column used was
      a Symmetry Shield with a mixture of acetonitrile-water (25:75) as mobile phase.
      Shrimp samples were fortified at CAP levels between 0.2 and 50 ng g(-1) with 5D
      CAP as internal standard. At these levels, accuracies lay between 101 and 110%
      and between-day reproducibilities were lower than 7.1%, expressed as the
      variation coefficient of the mean. Limit of decision (CCalpha) was 0.02 ng g(-1).
      Limit of quantitation (LOQ) was 0.2 ng g(-1).

PMID- 12798164
TI  - Determination of three major components of bitespiramycin and their major active
      metabolites in rat plasma by liquid chromatography-ion trap mass spectrometry.
AB  - The rapid, selective and sensitive liquid chromatographic-ion trap mass
      spectrometric (LC-MS(n)) method was developed and validated for determination of
      three major components (isovaleryspiramycins, ISV-SPMs) of a novel macrolide
      antibiotic bitespiramycin and their major active metabolites (spiramycins, SPMs)
      in rat plasma. The analytes ISV-SPMs, SPMs, internal standard roxithromycin and
      azithromycin were extracted from plasma samples by liquid-liquid extraction, and
      chromatographed on a C(18) column using two mobile phase systems. Detection was
      carried out on an ion trap mass spectrometer by selected reaction monitoring
      (SRM) mode via electrospray ionization (ESI). Three components (ISV-SPM I, II,
      III or SPM I, II, III) could be simultaneously determined within 6.5 min. Linear
      calibration curves were obtained in the concentration ranges of 4-200 ng/ml for
      ISV-SPM I and SPM I, 12-600 ng/ml for ISV-SPM II and SPM II, and 18-900 ng/ml for
      ISV-SPM III and SPM III. The intra- and inter-run precision (RSD), calculated
      from quality control (QC) samples were less than 8.8 and 10.4% for ISV-SPMs, and
      9.3 and 11.2% for SPMs, respectively. The method was applied for the evaluation
      of the pharmacokinetics of bitespiramycin in rats following peroral/intravenous
      administration.

PMID- 12798163
TI  - Liquid chromatographic-mass spectrometric assay for quantitation of imatinib and
      its main metabolite (CGP 74588) in plasma.
AB  - Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule
      inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor
      activity in patients with chronic myelogenous leukemia or gastrointestinal
      stromal tumors. We have developed a liquid chromatographic-electrospray
      ionization mass spectrometric (LC-MS) method for quantifying imatinib and its
      main metabolite (CGP 74588) in plasma. The assay uses deuterated imatinib as the
      internal standard; acetonitrile deproteination; a Phenomenex Luna C(18)(2) (5
      microm, 50 x 4.6 mm) reversed-phase analytical column; a gradient mobile phase of
      0.1% formic acid in methanol and water; and mass spectrometric detection using
      electrospray positive mode electron ionization. The assay has a lower limit of
      quantitation (LLOQ) of 30 ng/ml and is linear between 30 and 10000 ng/ml for both
      imatinib and CGP 74588. We demonstrated the suitability of this assay for
      imatinib using it to quantify the concentrations of imatinib and CGP 74588 in
      plasma of a patient given a 200-mg dose of imatinib orally. We believe that this
      LC-MS assay should be an important tool for future pharmacokinetic studies of
      imatinib.

PMID- 12798165
TI  - Membrane cartridges for endotoxin removal from interferon preparations.
AB  - The suitability of membrane cartridges for the removal of endotoxin from both
      distilled water and interferon preparations was examined. The endotoxin
      concentrations were reduced to 4.0 and 7.3 EU/ml, respectively, when about 4000
      ml of distilled water with 20 and 28 EU/ml were passed through the deoxycholate
      and chitosan immobilized membrane cartridges. When 200 ml of interferon
      preparation with endotoxin concentration more than 80 EU/ml and pH 3.9 were
      applied to a deoxycholate immobilized membrane cartridge at a flow-rate of 9
      ml/min, the endotoxin concentration was reduced to less than 10 EU/ml. However,
      if an interferon preparation of 450 ml, with more than 80 EU/ml of endotoxin and
      pH 3.9 was applied to the chitosan immobilized membrane cartridge at a flow-rate
      of 18 ml/min, the endotoxin concentration was reduced to less than 10 EU/ml.

PMID- 12798166
TI  - Gradient liquid chromatography of leucine-enkephalin peptide and its metabolites
      with electrochemical detection using highly boron-doped diamond electrode.
AB  - Boron-doped diamond thin film (BDD) electrodes have been used to study the
      oxidation reactions and to detect leucine-enkephalinamide (LEA) and its
      metabolites, tyrosine (T), tyrosyl-alanine (TA), tyrosyl-alanine-glycine (TAG)
      and leucine-enkephalin (LE) using cyclic voltammetry (CV), flow-injection
      analysis (FIA), and gradient liquid chromatography (LC) with amperometric
      detection. At diamond electrodes, well-defined and highly reproducible cyclic
      voltammograms were obtained with signal-to-background (S/B) ratios 5-10 times
      higher than those observed for glassy carbon (GC) electrodes. The analytical
      peaks of LC for LEA and its metabolites were well resolved. No deactivation of
      BDD electrodes was found after several experiments with standard as well as
      plasma samples, indicating high stability of the electrode. Calibration curves
      were linear over a wide range from 0.06 to 30 microM with regression coefficients
      of 0.999 for all compounds. The limits of detection obtained based on a signal-to
      noise ratio of 3:1 were 3, 2.2, 2.7, 20 and 11 nM for T, TA, TAG, LE and LEA,
      respectively. These values were at least one order lower than those obtained at
      GC electrodes, which has given limits of detection of 22.88, 20.64, 89.57, 116.04
      and 75.67 for T, TA, TAG, LE and LEA, respectively. Application of this method to
      real samples was demonstrated and validated using rabbit serum samples. This work
      shows the promising use of conducting diamond as an amperometric detector in
      gradient LC, especially for the analysis of enkephalinamide and its metabolites.

PMID- 12798167
TI  - Determination of haemoglobin A(1c) by liquid chromatography using a new cation
      exchange column.
AB  - The use of a new cation-exchange column, ProPac SCX-10, for the determination of
      haemoglobin A(1c) (HbA(1c)) by high-performance liquid chromatography is
      described. After optimization of the analytical method for the separation of the
      various isoforms of haemoglobin with the ProPac SCX-10 column, the method was
      applied to the determination of HbA(1c) in blood from 59 volunteers. Three of the
      59 had previously been diagnosed as diabetics. Interference studies for
      carbamylation, acetylation and pre-HbA(1c) were carried out via "in-vitro"
      experiments. No interference due to carbamylation was observed at the urea values
      normally found in uremic patients undergoing dialysis. No interference from pre
      HbA(1c) was detected either. The method is able to separate haemoglobin A
      (alpha(2)beta(2)), haemoglobin S (haemoglobin from sickle cell anaemia patients)
      and haemoglobin A(2) (alpha(2)delta(2)) without interference. The method of
      Hampel was applied to detect outliers. A value of 3.29+/-0.44% (2sigma) for
      HbA(1c) was obtained in the analysis of 56 blood samples from non-diabetics. This
      average value is lower than that reported by most of the methods currently used
      in routine analyses.

PMID- 12798168
TI  - Determination by liquid chromatography with fluorescence detection of total 7
      ethyl-10-hydroxy-camptothecin (SN-38) in beagle dog plasma after intravenous
      administration of liposome-based SN-38 (LE-SN38).
AB  - An HPLC- fluorescence method to quantitate total 7-ethyl-10-hydroxy-camptothecin
      (SN-38) in beagle dog plasma spiked with liposome based formulation of SN-38 (LE
      SN38) and using camptothecin (CPT) as the internal standard (I.S.) was developed
      and validated to support pharmacokinetics/toxicokinetics studies. Sample
      preparation was done by protein precipitation using acetonitrile with 0.5% acetic
      acid. The supernatant was evaporated, and reconstituted in acetonitrile-20 mM
      ammonium acetate, pH 3.5 (20:80, v/v). When injected onto a Zorbax SB-C(18) HPLC
      column SN-38 as well as I.S. were detected by fluorescence using an excitation at
      368 nm and emission at 515 nm. The SN-38 concentrations in samples were
      calculated from a standard curve of peak area ratios of SN-38 to the I.S. using
      weighted linear regression. The sensitivity limit for SN-38 was 1.00 ng/ml in
      beagle dog plasma with a precision (expressed as relative standard deviation) of
      12.4% and an accuracy (expressed as analytical recovery) of 104%. The assay was
      linear within the standard curve range of 1-750 ng/ml. Acceptable precision and
      accuracy were also obtained for concentrations over the balance of the standard
      curve range from between-run and within-run calculations.

PMID- 12798169
TI  - Measurement of piperaquine in plasma by liquid chromatography with ultraviolet
      absorbance detection.
AB  - Piperaquine (PQ) is an antimalarial drug enjoying a resurgence of use in
      combination with an artemisinin derivative because of parasite resistance to
      standard treatments. Its pharmacokinetic properties have not been characterised.
      An assay for PQ in plasma was developed using solvent extraction and liquid
      chromatographic separation on a Waters XTerra RP(18) column, with a mobile phase
      of 7% acetonitrile in water (containing 0.025% trifluoroacetic acid, 0.1% NaCl
      and 0.008% triethylamine) and UV detection at 340 nm. The assay was linear up to
      1000 microg/l. Intra- and inter-day relative standard deviations were <10% (5-500
      microg/l) and <21% (5-500 microg/l), respectively. Inter-day limits of
      quantitation and detection were 5 microg/l and 3 microg/l, respectively. A
      preliminary pharmacokinetic study in a patient who received 2.56 g of PQ
      phosphate orally with dihydroartemisinin as four doses over 32 h found an
      apparent steady-state volume of distribution of 447 l/kg, an apparent oral
      clearance 0.93 l/h/kg and a terminal half-life of 17.3 days.

PMID- 12798170
TI  - Simultaneous determination of gemcitabine and its metabolite in human plasma by
      high-performance liquid chromatography.
AB  - Gemcitabine (dFdC) is a pyrimidine antimetabolite with broad spectrum activity
      against tumors. In this paper, a normal-phase high-performance liquid
      chromatographic method was developed for the determination of the parent drug
      (dFdC) and its metabolite (dFdU) in human plasma. The described sample
      preparation procedure for determination of dFdC and dFdU is rapid, sensitive,
      reproducible and simple. The linear regression equations obtained by least square
      regression method, were area under the curve=0.0371 concentration (ng ml(
      1))+192.53 and 1.05.10(-4) concentration (ng ml(-1))-1.2693 for dFdC and dFdU,
      respectively. The assay for dFdC and dFdU described in the present report has
      been applied to plasma samples from a bladder cancer patient.

PMID- 12798171
TI  - Development and validation of a liquid chromatographic method for Casiopeina
      IIgly in rat plasma.
AB  - A sensitive and specific liquid chromatographic method using solid-phase
      extraction with Sep-pak cartridges has been developed for the determination of
      Casiopeina IIgly and validated over the linear range 2.5-50 microg/ml in rat
      plasma. The analysis was performed on a Symetry C(18) (5 microm) column with a
      Phenomenex C(18) precolumn. The mobile phase was methanol-water (58:42, v/v). The
      column effluent was monitored at 273 nm. The results showed that the assay is
      sensitive at 2.5 microg/ml. Maximum intra-day coefficient of variation was
      11.47%. The recovery based upon addition of internal standard to rat plasma was
      80.98%. The method was used to perform preclinical pharmacokinetic studies in rat
      plasma and was found to be satisfactory.

PMID- 12798172
TI  - Determination of polychlorinated biphenyls in serum using gas chromatography-mass
      spectrometry with negative chemical ionization for exposure estimation.
AB  - A sensitive and selective method for the determination of 24 polychlorinated
      biphenyls (PCBs) by gas chromatography-mass spectrometry with negative chemical
      ionization (GC-MS-NCI) was applied for the recent needs of occupational exposure
      in waste incineration. The three most abundant ions were used in determining
      compounds with at least five chlorine atoms in the PCB molecule. Selecting ions
      Cl(35) and Cl(37) for di-, tri-, and tetrachlorinated PCBs resulted in reliable
      quantification of these compounds. The detection limits for the 24 individual
      compounds varied from 0.01 to 0.08 microg/l. The recovery of the method was 113+/
      16%. Stability tests showed no degradation of the compounds studied during 6
      weeks. The sum of 24 PCB compounds measured from the sera of workers in a
      disposal plant was 1.9-10.9 microg/l, and 0.3-3.0 microg/l for controls,
      respectively. The mean proportion of the low chlorinated PCB compounds (with four
      or less chlorine atoms) was 20% for workers in the disposal plant and 14% for the
      controls.

PMID- 12798173
TI  - Determination of 3-keto-4-ene steroids and their hydroxylated metabolites
      catalyzed by recombinant human cytochrome P450 1B1 enzyme using gas
      chromatography-mass spectrometry with trimethylsilyl derivatization.
AB  - A protocol utilizing gas chromatography with selected ion monitoring mass
      spectrometric detection (GC-SIM-MS) using a simplified trimethylsilyl (TMS)
      derivatization protocol was developed and validated for the determination of
      hydroxylated metabolites of 3-keto-4-ene steroids such as testosterone,
      progesterone and androstenedione. Hydroxylated metabolites catalyzed by human
      CYP1B1 were extracted with methylene chloride and derivatized with BSTFA-10%
      TMCS. To get an optimal derivatizing condition, the effect of various incubation
      times and temperatures was evaluated. When the incubation temperature and time in
      the presence of the TMS derivatizing agent were increased, the 3-keto group
      became derivatized with TMS to form a 3-TMS derivative. To minimize the formation
      of the TMS ether on the 3-keto group, a reaction condition of 56 degrees C for 10
      min was used for the routine measurement of the steroids and their hydroxylated
      metabolite. Performance studies including linearity of calibration curves,
      extraction efficiency and precision were performed. Linearity of the calibration
      curves was satisfactory from 0.125 to 5 microM for most compounds except 21
      hydroxyprogesterone and 16alpha-hydroxyandrostenedione which deviated from
      linearity at the lower concentrations. Mean percentage extraction recoveries were
      greater than 80% for all compounds. Most compounds showed good precisions with
      C.V.s of within-day precision of less than 5% and C.V.s of between-day precision
      of less than 10%. The selected ion chromatograms from the recombinant human
      CYP1B1 incubations with testosterone, progesterone and androstenedione showed
      evidence of 6beta-, 16alpha-, 2alpha-, and 15alpha-hydroxytestosterone, 6alpha-
      and 16alpha-hydroxyprogesterone and 6alpha- and 16alpha-hydroxyandrostenedione,
      respectively. There was no significant interference associated with Escherichia
      coli membrane extracts in detecting hydroxylated metabolites. This procedure
      provides a rapid and sensitive method for the evaluation of steroid hydroxylation
      by CYP isoenzymes.

PMID- 12798174
TI  - Simultaneous determination of six HIV nucleoside analogue reverse transcriptase
      inhibitors and nevirapine by liquid chromatography with ultraviolet absorbance
      detection.
AB  - An accurate, sensitive and specific reversed-phase high-performance liquid
      chromatography assay for the simultaneous quantitative determination of the
      nucleoside reverse transcriptase inhibitors zalcitabine, lamivudine, didanosine,
      stavudine, zidovudine, and abacavir with the non-nucleoside reverse transcriptase
      inhibitor nevirapine in human blood plasma is described. The new Polarity dC
      C(18) silica column used in this method provides better resolution and peak shape
      than all other columns tested. Also, four different ultraviolet wavelengths were
      used for accurate and specific quantitation of the analytes. The method was
      validated over the range of 10-10000 ng/ml for all analytes except zalcitabine
      (10-5000 ng/ml). This method is accurate (average accuracies of three different
      concentrations ranged from 97.2 to 105%), and precise (within- and between-day
      precision measures ranged from 0.5 to 5.1% and 0.5 to 5.6%, respectively), and is
      currently being used for determination of plasma drug concentrations in our
      laboratory.

PMID- 12798175
TI  - Sedimentation field flow fractionation purification of immature neural cells from
      a human tumor neuroblastoma cell line.
AB  - The use of stem cells for therapeutic applications is now an important objective
      for the future. Stem cell preparation is difficult and time-consuming depending
      on the origin of cells. Sedimentation field flow fractionation (SdFFF) is an
      effective tool for cell separation, respecting integrity and viability. We used
      the human neuroblastic SH-SY5Y clone of the SK-N-SH cell line as a source of
      immature neural cells. Our results demonstrated that by using SdFFF cell sorter
      under strictly defined conditions, and immunological cell characterization, we
      are now able to provide, in less than 15 min, a sterile, viable, usable and
      purified immature neural cell fraction without inducting cell differentiation.

PMID- 12798176
TI  - Sensitive method for the quantitative determination of gemfibrozil in dog plasma
      by liquid-liquid cartridge extraction and liquid chromatography-tandem mass
      spectrometry.
AB  - A sensitive LC-MS/MS assay for the quantitative determination of gemfibrozil in
      dog plasma has been developed and validated and is described in this work. The
      assay involved the extraction of the analyte from 0.5-ml aliquots of dog plasma
      using Chem Elut cartridges and methyl tert.-butyl ether (MTBE). Chromatography
      was performed on a Metasil Basic column (50 x 2 mm I.D., 3 microm) using a mobile
      phase that consisted of 70:30 acetonitrile-ammonium acetate (1 mM, pH 5.0) with a
      flow-rate of 0.2 ml min(-1). The method showed excellent reproducibility with an
      inter- and intra-assay precision of <8.9% (%RSD), as well as excellent accuracy
      with an inter- and intra-assay accuracy between 99 and 101%. This method has a
      lower limit of quantitation (LLOQ) of 1.0 ng ml(-1) with a linear calibration
      range from 1.0 to 250 ng ml(-1). This new assay offers higher sensitivity and a
      much shorter run time over earlier methods.

PMID- 12798177
TI  - Simultaneous determination of bromvalerylurea and allylisopropylacetylurea in
      human blood and urine by gas chromatography-mass spectrometry.
AB  - We devised a sensitive and simple method to simultaneously determine
      bromvalerylurea and allylisopropylacetylurea in human blood and urine by gas
      chromatography-mass spectrometry. Bromvalerylurea and allylisopropylacetylurea
      were extracted using an Extrelut column with an internal standard, 2
      bromohexanoylurea, followed by derivatization with heptafluorobutyric anhydride.
      The derivatized extract was submitted to GC-MS analysis of EI-SIM mode. The
      calibration curves of both compounds were linear in the concentration range from
      0.01 to 10 microg/ml in both blood and urine samples. The lower limits of
      detection of bromvalerylurea and allylisopropylacetylurea were 0.005 and 0.005
      microg/ml, respectively. This method proved most useful in accurately identifying
      these drugs in blood and urine from an autopsied individual.

PMID- 12798178
TI  - Simultaneous enantiospecific separation and quantitation of mephenytoin and its
      metabolites nirvanol and 4'-hydroxymephenytoin in human plasma by liquid
      chromatography.
AB  - A high-performance liquid chromatographic method for the enantiospecific
      quantitation of S- and R-mephenytoin and its metabolites S- and R-nirvanol and S-
      and R-4'-hydroxymephenytoin in plasma is described. The compounds were separated
      using a reversed-phase C(2) column in tandem with a chiral alpha(1)-acid
      glycoprotein column and were detected using ultraviolet detection at 205 nm. The
      lower limit of quantification was 10 ng/ml for all compounds using 0.5 ml human
      plasma (intra-day coefficient of variation <13%, accuracy <+/-20%). The method
      was validated for human plasma in the concentration range 10-2000 ng/ml for each
      of the six compounds. The method allows for the simultaneous characterisation of
      the metabolic capacity of two human drug-metabolising enzymes, CYP2C19 and
      CYP2B6, and may be used when investigating polymorphisms or changes in activity
      of these two enzymes.

PMID- 12798179
TI  - Determination of glycosaminoglycan monosaccharides by capillary electrophoresis
      using laser-induced fluorescence detection.
AB  - A newly developed capillary electrophoretic method using laser-induced
      fluorescence detection (CE-LIF) for the analysis of monosaccharides released from
      acid hydrolysis of glycosaminoglycans was studied. The method was compared with a
      previously published method using indirect LIF detection (CE-ILIF). For the CE
      LIF method, electrophoretic conditions for the separation of the monosaccharides
      derivatised with 8-aminopyrene-1,3,6-trisulfonate (APTS) were optimised. The best
      separations were obtained using 100 mM acetate at pH 4.5 as running buffer. The
      influence of the injection vial volume on the precision and stability of the
      sample in different conditions was studied. The detection limits of the CE-LIF
      method were found to be 0.4-0.6 nM, while those obtained by CE-ILIF ranged from
      11.4 to 14.3 microM. Other quality parameters of the method, such as run-to-run
      precision, day-to-day precision, and linearity were also determined. Finally, the
      new method was applied to the analysis of the acid hydrolysis products from a
      glucosaminoglycan (heparin) and a galactosaminoglycan (dermatan sulfate) and
      cross-contamination between the two solutions was determined. The high
      sensitivity of the new method allows the determination of dermatan sulfate
      contaminations in a heparin raw sample down to 0.04% (w/w) and broadens the
      practical applicability of CE-LIF for the quantitation of the endogenous levels
      of glycosaminoglycans in animal samples and for pharmacokinetic control after
      therapeutical heparin administration.

PMID- 12798180
TI  - Development and validation of a capillary zone electrophoresis method for the
      determination of ephedrine and related compounds in urine without extraction.
AB  - A capillary zone electrophoresis (CZE) method, with UV detection and in the
      presence of dimethyl-beta-CD, was optimized by means of an experimental design
      for the separation and the simultaneous quantitation of ephedrine,
      pseudoephedrine, norephedrine (phenylpropanolamine) and norpseudoephedrine
      (cathine) in urine without any extraction. In this application, the optimization
      of the analytical conditions with an experimental design was preferred to a
      univariate study. Therefore, a central composite design was used and the
      following factors were investigated and varied simultaneously: buffer
      concentration, buffer pH and dimethyl-beta-CD concentration. In order to evaluate
      the influence of each experimental parameter on the analytical separation, the
      resolutions between the four compounds, as well as the separation time and
      generated current were observed and established as responses of the experimental
      design. A model was obtained for each response by linear multiple regression of a
      second-degree mathematical expression. After acceptance of the mathematical
      models, the most favorable conditions were determined by maximizing the
      resolutions between the four compounds and by setting the other responses at
      threshold values. Successful results were obtained with a 260 mM Tris-phosphate
      buffer at pH 3.5 in the presence of 13.3 mM dimethyl-beta-CD at 25 degrees C and
      with an applied voltage of 30 kV. Under these optimized conditions, a baseline
      separation of the four compounds was achieved in less than 6 min. The method was
      validated in terms of precision, linearity, accuracy and successfully applied for
      the determination of these compounds in urine samples without any extraction as
      well as in nutritional supplements.

PMID- 12798181
TI  - Liquid chromatography with amperometric detection using functionalized multi-wall
      carbon nanotube modified electrode for the determination of monoamine
      neurotransmitters and their metabolites.
AB  - The fabrication and application of a novel electrochemical detection (ED) method
      with the functionalized multi-wall carbon nanotubes (MWNTs) chemically modified
      electrode (CME) for liquid chromatography (LC) were described. The
      electrochemical behaviors of dopamine (DA) and other monoamine neurotransmitters
      at the CME were investigated by cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV). The results indicated that the CME exhibited efficient
      electrocatalytic effects on the current responses of monoamine neurotransmitters
      and their metabolites with high sensitivity, high stability and long-life
      activity. In LC-ED, DA, norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol
      (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), 5
      hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) had good and stable
      current responses at the CME. The linear ranges of seven analytes were over four
      orders of magnitude and the detection limits were 2.5 x 10(-10) mol/l for DA, 2.5
      x 10(-10) mol/l for NE, 5.0 x 10(-10) mol/l for MHPG, 3.0 x 10(-10) mol/l for
      DOPAC, 3.5 x 10(-10) mol/l for 5-HT, 6.0 x 10(-10) mol/l for 5-HIAA, 1.25 x 10(
      9) mol/l for HVA. The application of this method coupled with microdialysis
      sampling for the determination of monoamine neurotransmitters and their
      metabolites in Parkinsonian patients' cerebrospinal fluid was satisfactory.

PMID- 12798182
TI  - Liquid chromatographic assay for the antiviral nucleotide analogue tenofovir in
      plasma using derivatization with chloroacetaldehyde.
AB  - A sensitive and selective reversed-phase liquid chromatographic assay for
      tenofovir in human plasma has been developed and validated. Tenofovir was
      isolated from a 200 microl plasma sample using protein precipitation with
      trichloroacetic acid. The fluorescent 1,N(6)-etheno derivative is formed at 98
      degrees C in the buffered extract with chloroacetaldehyde. This derivative was
      analysed using gradient ion-pair liquid chromatography and fluorescence detection
      at 254 nm for excitation and 425 nm for emission. In the evaluated concentration
      range (20-1000 ng/ml), the intra-day precision was 4% and the inter-day precision
      was 5-6%. An accuracy of between 97 and 110% was determined. The lower limit of
      quantification was 20 ng/ml with an inter-day precision of 11%, an intra-day
      precision of 12% and an accuracy of 103%. The assay is subject to interference
      from co-administered abacavir. The usefulness of the assay was demonstrated for
      samples obtained from an HIV-infected patient treated with tenofovir.

PMID- 12798183
TI  - Multidimensional gas chromatography-mass spectrometry for tracer studies of fatty
      acid metabolism via stable isotopes in cultured human trophoblast cells.
AB  - The determination of placental fatty acid metabolism using stable isotope-labeled
      tracers was investigated in the human placental choriocarcinoma (JAR) cell line.
      Stable isotope incorporation was measured by MDGC-MS. The cultured trophoblast
      cells incorporated and metabolized the essential fatty acids to long-chain
      polyunsaturated fatty acids. The described method enables the detection of a low
      Delta(6)-desaturase activity in this human placental cell line. The developed
      MDGC-MS method allows the assessment of long-chain polyunsaturated fatty acid
      biosynthesis in cultured cells with high sensitivity and selectivity. In this
      respect, tracer studies with MDGC-MS will be a powerful tool to clarify the
      significance of placental fatty acid metabolism.

PMID- 12798184
TI  - Quantification of tamoxifen and three metabolites in plasma by high-performance
      liquid chromatography with fluorescence detection: application to a clinical
      trial.
AB  - A sensitive and reproducible assay employing liquid-liquid extraction and high
      performance liquid chromatography with fluorescence detection for the
      quantification of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen, and Z-4
      hydroxy-N-desmethyltamoxifen in human plasma is described. The compounds and
      internal standard, propranolol, were separated with a cyano column and a mobile
      phase of acetonitrile-20 mM potassium phosphate buffer (pH 3; 35:65, v/v) then
      detected with fluorescence using a modified version of a method originally
      described by Fried and Wainer [J. Chromatogr. B 655 (1994) 261]. The coefficients
      of variation for the midpoint of the standard curve for each compound were less
      than 10%. This method was applied to a pharmacokinetic study of tamoxifen
      disposition in breast cancer patients.

PMID- 12798185
TI  - Development of a liquid chromatographic method for bioanalytical applications
      with sildenafil.
AB  - An improved HPLC method was developed for the determination of sildenafil
      concentrations in plasma. Analysis of sildenafil in plasma samples was simplified
      by utilizing a one-step liquid-liquid extraction after alkaline treatment of only
      1 ml of plasma. The lower limit of quantitation was 10 ng/ml with a coefficient
      of variation of less than 20%. A linear range was found to exist from 10 to 1000
      ng/ml. This HPLC method was validated with precisions (coefficient of variation,
      C.V.) for inter- and intra-day runs of 0.41-11.15% and 0.36-8.05%, respectively,
      and accuracies (the relative error of the mean, REM) for inter- and intra-day
      runs of -8.72-6.81% and 0.41-11.15%, respectively. A bioavailability study of
      sildenafil was performed on one normal healthy male volunteer by analyzing
      sildenafil plasma concentrations with this validated HPLC method. Results
      demonstrated that this HPLC method is appropriate for applications to
      bioavailability studies of sildenafil. In addition, an example of the influence
      of the co-administration of grapefruit juice on sildenafil pharmacokinetics in a
      healthy volunteer is presented.

PMID- 12798186
TI  - Enhanced purification of plasmid DNA using Q-Sepharose by modulation of alcohol
      concentrations.
AB  - Ion-exchange chromatography is one of the most commonly used methods for plasmid
      preparation. In this study a modified method was used to purify plasmid from
      bacterial lysate using Q-Sepharose. Incorporation of alcohols into the washing
      buffers enhanced the separation of plasmid from RNA and proteins. The use of
      isopropanol and ethanol achieved a high yield and purity whereas the use of
      methanol failed to improve the plasmid purification using Q-Sepharose by batch
      adsorption-desorption. Stepwise elution containing various concentrations of
      isopropanol and NaCl was used in preparative chromatography to enhance the
      plasmid purification. The same stepwise elution was applied to the chromatography
      columns packed with 0.5, 20, and 200 ml of Q-Sepharose for plasmid purification
      from 7.5, 300, and 3000 ml bacterial broth, respectively. Complete separation of
      DNA from RNA and proteins was achieved under gravity flow by modulation of the
      alcohol concentrations in the stepwise elution. These three scales of
      chromatography maintained an approximate plasmid yield and the purified plasmid
      contained undetectable levels of RNA and protein.

PMID- 12798187
TI  - Egg yolk phosvitin: preparation of metal-free purified protein by fast protein
      liquid chromatography using aqueous solvents.
AB  - Two chromatographic methods for hen egg yolk phosvitin purification avoiding
      organic solvents were evaluated. Hydrophobic interaction and ion-exchange
      chromatographies were applied to isolated phosvitin. Hydrophobic interaction
      chromatography has better capacity than ion-exchange chromatography to
      fractionate phosvitin in their different polypeptides, but its protein yield was
      lower (0.7 vs. 1.7% of egg yolk dry matter). Finally, ion-exchange chromatography
      was selected and allowed to fractionate phosvitin polypeptides, including the
      recovering of phosphoproteins with high electrophoretic mobility: phosvettes.
      Highly purified (>98%) and free metal protein was obtained in reduced time.
      Phosvitin polypeptide heterogeneity was evidenced.

PMID- 12798188
TI  - Simultaneous determination of N-butyramide-tacrine and tacrine in mouse plasma
      and brain homogenate by high-performance liquid chromatography with a simple
      gradient solvent system.
AB  - A novel reversed-phase HPLC method was developed for the simultaneous
      determination of tacrine (THA) and the newly synthesized prodrug (N-butyramide
      THA, BTHA) in mouse plasma and brain homogenate. The assay involves
      deproteinisation and subsequent detection at 240 nm with a gradient solvent
      system. Retention times were 18.5 and 9.3 min for BTHA and THA, respectively.
      Average recoveries for the analytes were 80.7% (BTHA) and 76.6% (THA) from
      plasma, and 75.0% (BTHA) and 68.4% (THA) from brain homogenate. Linear responses
      were observed over a wide range (0.25-20 microg/ml for BTHA in plasma and in
      brain homogenate, 0.025-20 microg/ml for THA in both matrices). Both BTHA and THA
      degraded from the prodrug can be detected even 12 h after intravenous
      administration of BTHA, indicating that BTHA is a promising prodrug for brain
      targeting.

PMID- 12798189
TI  - Liquid chromatography studies on the pharmacokinetics of phentermine and
      fenfluramine in brain and blood microdialysates after intraperitoneal
      administration to rats.
AB  - A highly sensitive and simple HPLC method with fluorescence detection for the
      determination of phentermine (Phen), fenfluramine (Fen) and norfenfluramine
      (Norf, the active metabolite of Fen) in rat brain and blood microdialysates has
      been developed. The brain and blood microdialysates were directly subjected to
      derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (DIB-Cl)
      in the presence of carbonate buffer (0.1 M, pH 9.0) at room temperature. The
      chromatographic conditions consisted of an ODS column and mobile phase
      composition of acetonitrile and water (65:35, v/v) with flow rate set at 1.0
      ml/min. The detection was performed at excitation and emission wavelengths of 325
      and 430 nm, respectively. Under these conditions, the DIB-derivatives of Phen,
      Fen and Norf were well separated and showed good linearities in the studied
      ranges (5-2000 nM for Phen and 10-2000 nM for Norf and Fen) with correlation
      coefficients greater than 0.999. The obtained detection limits were less than 23
      fmol on column (for the three compounds) in both brain and blood microdialysates
      at a signal-to-noise ratio of 3 (S/N=3). The intra- and the inter-assay
      precisions were lower than 10%. The method coupled with microdialysis was applied
      for a pharmacokinetic drug-drug interaction study of Phen and Fen following
      individual and combined intraperitoneal administration to rats. In addition,
      since the role of protein binding in drug interactions can be quite involved, the
      method was applied for the determination of total and free Phen and Fen in rat
      plasma and ultrafiltrate, respectively. The results showed that Fen and/or Norf
      significantly altered the pharmacokinetic parameters of Phen in both blood and
      brain but did not alter its protein binding. On the other hand, there was no
      significant difference in the pharmacokinetics of Fen when administered with
      Phen.

PMID- 12798190
TI  - Improved simultaneous determination method of beta-carotene and retinol with
      saponification in human serum and rat liver.
AB  - Among the many simultaneous determination methods for carotenoid and retinoid,
      there are only a few reports including the saponification process. However, the
      yields of beta-carotene and retinol were higher when using this process. In this
      study, the analytical conditions, including saponification, were investigated.
      The extraction solvent was n-hexane and the sample solvent was HPLC mobile phase
      in the beta-carotene and retinol analysis. BHT as an antioxidant was added at
      concentrations of 0.125 and 0.025%, respectively, to ethanol and n-hexane phase
      in the extraction process for serum. The recovery rates were 99.7, 93.7 and 98.3%
      for beta-carotene, retinol and retinyl palmitate in serum, respectively, and
      107.1, 92.8 and 98.8% for beta-carotene, retinol and retinyl palmitate in liver,
      respectively. The within-day coefficients of variation (C.V.) were 6.0% for serum
      and 4.7% for liver in the case of beta-carotene, 7.1% for serum, and 5.1% for
      liver in the case of retinol. The between-day coefficients of variation were 2.7%
      for serum and 2.7% for liver in the case of beta-carotene, and for retinol, 6.4%
      for serum and 2.7% for liver.

PMID- 12798191
TI  - Analysis of secretory immunoglobulin A in human saliva by laser-induced
      fluorescence capillary electrophoresis.
AB  - The utility of capillary electrophoresis (CE) has been demonstrated for the
      analysis of secretory immunoglobulin A (sIgA) in human saliva. The amount of sIgA
      in saliva correlates with immune status. For detecting salivary sIgA, laser
      induced fluorescence was conducted in this report for signal amplification. sIgA
      and anti-sIgA antibody were labeled with cyanine fluorescence (Cy5) for
      competitive immunoassay and non-competitive analysis, respectively. Cy5 was
      excited by He-Ne laser with a wavelength of 635 nm, with maximum emission at 670
      nm. Migration time during electrophoresis depended on whether sIgA-Cy5 was mixed
      with antibody or anti-sIgA-Cy5 mixed with sIgA to form Ag-Ab complex. The results
      indicated that CE competitive immunoassay was effective for analyzing serum sIgA,
      but not for salivary sIgA. However, salivary sIgA can be analyzed by complex
      formation assay. The peak area of the complex was proportional to the amount of
      sIgA added. A standard linear regression curve was generated using purified sIgA.
      From this standard curve, the amount of sIgA from saliva of either normal or
      immunocompromised patients can be calculated from the Ag-Ab complex peak area.

PMID- 12798192
TI  - Guidelines for analytical method development and validation of biotechnological
      synthesis of drugs. Production of a hydroxyprogesterone as model.
AB  - In connection with biotechnological synthesis of pharmaceutical drugs, validated
      methods for quantification of both product and substrate at different time
      intervals are essential for proper calculation of rate coefficients. In this
      field, there still exist no guidelines for analytical validation, unlike the
      situation in the bioanalytical field. Therefore, in this study the detailed
      guidelines by FDA for bioanalytical method validation were applied to a typical
      biotechnological process; the enzymatic synthesis of 9alpha-hydroxyprogesterone
      in E. coli using progesterone as substrate. The process liquid was extracted and
      analyzed using an HPLC-DAD system. The quality control (QC) samples of the
      product demonstrated excellent precision (C.V.<1.5%) and accuracy between 99.3
      and 107%. The study showed that the recommendations and the validation terms for
      bioanalytical methods can be used also for biotechnological production, but with
      some important exceptions. The tolerances (C.V. values) of the validation terms
      should be much narrower; the internal standard (I.S.) must be present in the
      process liquid before the start of the process and must be much different in
      structure from the substrate (so as not to participate in the biotechnological
      process). In addition, the selectivity must be checked very frequently during the
      process due to the changes in the blank process liquid with time.

PMID- 12798193
TI  - Liquid chromatographic determination of minocycline in brain-to-plasma
      distribution studies in the rat.
AB  - An isocratic reversed-phase high-performance liquid chromatographic procedure was
      developed for the determination of minocycline in rat plasma and brain and
      applied to brain-to-blood (plasma) distribution studies. The procedure is based
      on isolation of the compound and the internal standard (either demeclocycline or
      tetracycline may be used) from plasma and brain constituents using the Oasis HLB
      cartridge, with satisfactory recovery and specificity, and separation on a
      Symmetry Shield RP8 (15 cm x 4.6 mm, 3.5 microm) column coupled with a UV
      detector set at 350 nm. The assay was linear over a wide range, with a lower
      limit of quantification of 50 ng ml(-1) or g(-1), using 0.2 ml of plasma and
      about 200 mg of brain tissue. Precision and accuracy were acceptable. In the rat
      minocycline crossed the blood-brain barrier slowly, achieving mean brain
      concentrations between 30 and 40% of the equivalent systemic exposure, regardless
      of the dose and route of administration.

PMID- 12798194
TI  - Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host
      defense peptides.
AB  - Hemoglobin is a known source of biologically active peptides with various
      functions. In the present study, we report for the first time the existence of
      natural processed hemoglobin fragments exhibiting antimicrobial activity in
      humans. Two antimicrobial hemoglobin-derived peptides were purified from a human
      placental peptide library by consecutive chromatographic steps tracking the
      maximum growth inhibitory activity against Escherichia coli BL21. These peptides,
      consisting of 17 and 36 amino acid residues, were identified as being C-terminal
      fragments of gamma-hemoglobin and beta-hemoglobin, respectively. The
      antimicrobial beta-hemoglobin fragment was also purified from lysed erythrocytes,
      demonstrating that proteolytic degradation of hemoglobin into small bioactive
      peptides already starts inside erythrocytes. The identified peptides inhibit the
      growth of Gram-positive and Gram-negative bacteria and yeasts in micromolar
      concentrations. Moreover, by LPS-binding, the beta-hemoglobin fragment reduces
      biological activity of endotoxins. In contrast, even at high concentrations, the
      identified antimicrobial hemoglobin peptides do not exhibit toxic activity on
      human primary blood cells. We conclude that antimicrobial hemoglobin-derived
      peptides could be important effectors of the innate immune response killing
      microbial invaders.

PMID- 12798195
TI  - Technique validation by liquid chromatography for the determination of acyclovir
      in plasma.
AB  - In this research project, a high-performance liquid chromatography (HPLC) method
      was developed for the determination of acyclovir (ACV) in plasma. The plasma
      samples, recharged with acyclovir and in presence of 5'-N
      methylcarboxyamidoadenosine (MECA) as an internal standard, were purified using a
      solid-phase extraction technique with Waters Oasis HLB columns. The separation of
      the components from the extract was carried out in a LiChrospher 100 RP-18 column
      for further ultraviolet detection at a wavelength range of 250-260 nm. The mobile
      phase composition was 18% acetonitrile, sodium dodecylsulphate 5 mM and phosphate
      buffer at pH 2.6 with an analysis time of 13 min per sample. The average
      retention time for acyclovir was of 5.0 min and for the internal standard 11.2
      min. The calibration curve was linear ranging between 0.05 and 1.80 microg/ml.
      The detection limit was 0.006 microg/ml with a quantification limit of 0.020
      microg/ml. The ACV recuperation percentage for 250 microl of plasma was between
      94.7 and 109.7% with a coefficient of variation not higher than 5.2%. This method
      was developed and validated for use in bioavailability and bioequivalence
      studies.

PMID- 12798196
TI  - Inactivation of acrolein by sodium 2-mercaptoethanesulfonate using headspace
      solid-phase microextraction gas chromatography and mass spectrometry.
AB  - Acrolein, the metabolite of cyclophosphamide and ifosphamide, is an irritant of
      mucous membranes and seems to play an important role in hemorrhagic cystitis.
      Several methods are available to reduce the risk of hemorrhagic cystitis. Mesna
      is a regional detoxificant which inactivates acrolein. However, the interaction
      of mesna and acrolein has never been reported because no available method can
      detect acrolein. In this study, we measured acrolein to evaluate the effect of
      mesna in urine or phosphate-buffered saline using a headspace-solid-phase
      microextraction gas chromatography and mass spectrometry method which we had
      previously established. We also investigated the effect of mesna at different
      conditions of pH. Mesna was effective in a dose-dependent (10 microM to 20 mM)
      fashion in both urine and phosphate-buffered saline and completely inactivated
      acrolein at concentrations over 10 mM. Furthermore, mesna was more effective in
      alkaline conditions than in acid.

PMID- 12798197
TI  - Sensitive method for the quantification of urinary pyrimidine metabolites in
      healthy adults by gas chromatography-tandem mass spectrometry.
AB  - Enzyme deficiencies in pyrimidine metabolism are associated with a risk for
      severe toxicity against the antineoplastic agent 5-fluorouracil. To assess
      whether urinary levels of pyrimidines and their metabolites can be used for
      predicting patients' individual phenotype, a new gas chromatographic-tandem mass
      spectrometric method was developed which allows the simultaneous determination of
      uracil and thymine and their metabolites dihydrouracil, dihydrothymine, beta
      ureidopropionic acid, beta-ureidoisobutyric acid, and the amino acids beta
      alanine and beta-aminoisobutyric acid in human urine. Small aliquots (2-20
      microl) of the urine samples were evaporated and derivatized to the tert.
      butyldimethylsilyl derivatives before quantification, using the respective stable
      isotope-labelled analogues as internal standards. Analytical variation was
      acceptable with an intra-day imprecision (RSD) below 10%, for beta
      ureidoisobutyric acid below 15%. The method was used for investigating the
      stability of urine samples and the influence of urine collection at different
      times.

PMID- 12798198
TI  - Pharmaceutical profiling method for lipophilicity and integrity using liquid
      chromatography-mass spectrometry.
AB  - A method is described for the simultaneous profiling of sample lipophilicity,
      integrity, and purity. The method is rapid and is applicable to high throughput
      profiling of pharmaceutical properties in drug discovery. A short Polaris C(18)
      column is used with a rapid, wide-polarity mobile phase gradient, UV detection,
      and MS analysis. The lipophilicity of each component is estimated from a
      calibration curve using six drug or organic compounds and plotting their
      respective measured retention time versus LogD(7.4) (literature). The correlation
      of LogD(7.4) (literature) to LogD(7.4) (HPLC) for 60 structurally diverse drugs
      has a correlation coefficient r(2) of 0.89. The method is applicable to compounds
      with MW>200 and retention time>1.5 min for rapid, initial pharmaceutical
      profiling in drug discovery.

PMID- 12798199
TI  - Simultaneous determination of levomepromazine, midazolam and their major
      metabolites in human plasma by reversed-phase liquid chromatography.
AB  - A sensitive and reliable high-performance liquid chromatographic (HPLC) assay is
      a prerequisite for pharmacokinetic analysis of continuous infusion of
      levomepromazine adjuvant to midazolam. We developed such a method to determine
      the levels of levomepromazine, midazolam and their major metabolites
      (levomepromazinesulfoxide, desmethyl-, didesmethyllevomepromazine, O
      desmethyllevomepromazine and alpha-hydroxy-midazolam) simultaneously.
      Desmethylclomipramine was used as an internal standard (I.S.). The lower limit of
      quantification of this assay was set for levomepromazine 4.1 microg/l,
      levomepromazinesulfoxide 4.9 microg/l, O-desmethyllevomepromazine 18.4 microg/l,
      alpha-hydroxymidazolam 26.6 microg/l, midazolam 23.4 microg/l,
      didesmethyllevomepromazine 15.8 microg/l, and desmethyllevomepromazine 6.6
      microg/l. The between- and within day assay variations were commonly below 5%.
      The recovery in human plasma for the different analytes varied between 85 and
      11%. The accuracy of this assay varied between 95 and 105% for the different
      concentrations. The linearity of this assay was set between 25 and 800 microg/l
      (r(2)>0.999 of the regression line). The first results of pharmacokinetic
      analysis of midazolam indicated that half-life varied between 1.1 and 1.9 h.
      Pharmacokinetic analysis using a one-compartment model of levomepromazine
      revealed that the apparent volume of distribution was 4.1+/-2.4 l per kg lean
      body mass and the metabolic clearance was 309+/-225 l per hour per 70 kg. This
      assay proved to be robust and reproducible. It can reliably be used for further
      study of the pharmacokinetics of continuous infusion of levomepromazine.

PMID- 12798200
TI  - Determination of 13C and 15N enrichments of urea in plasma by gas chromatography
      combustion isotope ratio mass spectrometry and gas chromatography-mass
      spectrometry using the 2-methoxypyrimidine derivative.
AB  - We describe a GC-MS and GC-c-IRMS method for the determination of labeled urea
      tracer enrichments in plasma as a result of combined 13C- and 15N(2)-urea
      infusion experiments in piglets. Urea was converted into 2-methoxypyrimidine, a
      stable derivative, suited for analyses by both GC-MS and GC-c-IRMS. Using
      calibration curves for the respective working ranges (13C-urea: 0-1% APE; 15N(2)
      urea: 0-7% MPE) enrichments were established in single point measurements; for
      15N(2)-urea as values+/-0.15% MPE (95% confidence interval); for 13C-urea as
      values+/-0.02% APE (95% confidence interval). 15N(1)-urea enrichments were
      determined by measurement of the same sample with GC-c-IRMS and GC-MS.
      Subtraction of the 13C specific GC-c-IRMS data from the nondiscriminating GC-MS
      data for the sum of 13C- and 15N(1)-urea resulted in 15N(1)-urea enrichments+/
      0.15% MPE (95% confidence interval). Application of the method in a combined 13C
      urea bolus and 15N(2)-urea primed constant infusion experiment in piglet was
      demonstrated.

PMID- 12798201
TI  - Pullulan-cyclodextrin microspheres. A chromatographic approach for the evaluation
      of the drug-cyclodextrin interactions and the determination of the drug release
      profiles.
AB  - Pullulan microspheres containing cyclodextrin (CyD) were obtained by chemical
      crosslinking with epichlorohydrin of an alkaline solution of pullulan (Pul) and
      alpha-, beta- or gamma-CyD. The amount of alpha-, beta- and gamma-CyD in
      microspheres was 120, 156, and 138 micromol/g, respectively, as determined from
      the percentage of iodine incorporated in the hydrophobic cavity of CyD's.
      Microspheres were packed in a glass column and the liquid chromatographic
      behaviour by isocratic elution of different drugs or typical organic compounds
      (TOC), taken as model drugs, was investigated. The increase of the retention
      volume (V(R)) of each compound, depending on the interaction(s) between CyD's
      cavity and the considered molecule, is characterized by a broadening of the
      peaks. The interaction coefficient K, corresponding to the ratio between the V(R)
      value of each tested molecule on Pul-alpha-, Pul-beta- and Pul-gamma-CyD active
      stationary phase and the V(R) value of benzoic acid on St/maltodextrin neutral
      stationary phase, was determined. According to K values, the accurate prediction
      can be done on the potential drugs to be conditioned in suitable CyD cavity.
      Values of K allow to anticipate the release profiles of drugs considered.

PMID- 12798202
TI  - Simultaneous determination of ketamine and xylazine in canine plasma by liquid
      chromatography with ultraviolet absorbance detection.
AB  - An isocratic reversed-phase high-performance liquid chromatographic method for
      the simultaneous determination of ketamine and xylazine in canine plasma is
      described. Plasma samples (500 microl) are cleaned up via liquid-liquid
      extraction. The analytes and the internal standard clonidine are separated on a
      cyano (CN) column using a mobile phase containing acetonitrile-0.005 M phosphate
      buffer adjusted to pH 5.5 (3:2) at a detection wavelength of 215 nm. The method
      was validated according to specificity, sensitivity, accuracy and reproducibility
      and was used to determine the plasma concentrations of both compounds in dogs
      after intramuscular injection.

PMID- 12798203
TI  - Liquid chromatographic determination of hydroxyproline in tissue samples.
AB  - We describe a reversed-phase assay of hydroxyproline in rat lung tissue using
      sarcosine for the internal standard and pre-injection reaction with both o
      phthalaldehyde (OPA) and 9-fluorenylmethylchloroformate (FMOC). Intra-assay
      variability in the concentration range of 25-500 microM hydroxyproline was less
      than 1%. Normal rat (left) lung was found to have a hydroxyproline content of
      1.08+/-0.18 mg/lung. This ability to measure minute amounts of hydroxyproline is
      being applied to the measure of collagen and pathological fibrosis.

PMID- 12798204
TI  - Chemical coding of sympathetic neurons controlling the tarsal muscle of the rat.
AB  - Sympathetic axons in the upper eyelid and in tissues in the superior retro
      orbital space were examined for NPY immunoreactivity. Sympathetic nerve terminals
      containing co-localised NPY were associated with blood vessels, the conjunctiva
      and the Meibomian glands. The acini of the Harderian gland completely lacked
      sympathetic innervation. Sympathetic axons lacking NPY were only found in the
      tarsal muscle. In addition, a minority of terminals, located in the more proximal
      part of the tarsal muscle, contained weak immunoreactivity to NPY. Injections of
      the retrograde tracer, Fast Blue, into the eyelid or retro-orbital space labelled
      postganglionic somata in the superior cervical ganglion. While many retrogradely
      labelled somata were immunoreactive for NPY, around half lacked NPY
      immunoreactivity and so are likely to project to the tarsal muscle. Most of the
      retrogradely labelled postganglionic somata lacking NPY were surrounded by
      terminals immunoreactive for met-enkephalin, leu-enkephalin and met-enkephalin
      arg-gly-leu which were all found to be present in the same nerve terminals.
      Sectioning the cervico-sympathetic trunk eliminated all enkephalin-immunoreactive
      pericellular baskets. Many enkephalin-immunoreactive pericellular terminals
      contained co-localised VAChT, calretinin and calbindin immunoreactivity, but
      completely lacked nitric oxide synthase immunoreactivity. A second population of
      nerve terminals that were immunoreactive for nitric oxide synthase also
      surrounded tarsal muscle-projecting neurons, but these terminals lacked
      immunoreactivity to enkephalin. Thus, postganglionic neurons projecting to the
      tarsal muscle are of at least two chemical phenotypes (with or without NPY) and
      they receive convergent input from at least two populations of preganglionic
      neurons with distinctive chemical phenotypes.

PMID- 12798205
TI  - Estrogen receptor expression in lumbosacral dorsal root ganglion cells
      innervating the female rat urinary bladder.
AB  - We have investigated whether bladder afferent neurons are likely to be targets
      for circulating estrogens by mapping estrogen receptor (ER) distribution in
      lumbosacral dorsal root ganglia (DRG) of adult female rats. Sensory neurons
      innervating either the detrusor or trigone regions were identified by application
      of fluorescent retrograde tracer dyes to the bladder wall. Labelled neurons were
      classified by their immunoreactivity for either type of ER (ERalpha or ERbeta)
      and further compared with subpopulations of neurons containing substance P,
      calcitonin gene-related peptide and vanilloid receptor (a marker of polymodal
      nociceptors). Both ER types were expressed in numerous sensory neurons of either
      upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost
      complete coexpression of ERalpha and ERbeta. ER-positive neurons were mainly
      small-medium size (18-25-microm diameter), indicating that they may be
      nociceptors and/or supply visceral targets. Most bladder-projecting neurons
      expressed ERs and the majority of these also expressed neuropeptides or vanilloid
      receptor. Afferent neurons supplying detrusor and trigone regions had similar
      immunohistochemical features. About a third of the bladder-projecting neurons
      expressed both ER and vanilloid receptor, suggesting a mechanism by which
      estrogens could influence bladder pain. The prevalence of different chemical
      classes of ER-positive bladder-projecting neurons was reflected throughout the
      entire population of neurons in dorsal root ganglia of these spinal levels,
      suggesting that neurons supplying other pelvic visceral targets may have similar
      chemical profiles. These results suggest that many functional classes of sensory
      neurons innervating the lower urinary tract are likely to be targets for
      circulating estrogens, including many nociceptor neurons. The coexistence of
      ERalpha and ERbeta suggests a broad range of potential mechanisms by which
      estrogens may exert their genomic effects in this system.

PMID- 12798206
TI  - Electrocardiographic changes associated with the nasopharyngeal reflex in
      conscious rabbits: vago-sympathetic co-activation.
AB  - Electrocardiographic responses were assessed in conscious rabbits when the
      nasopharyngeal reflex was elicited by inhalation of formaldehyde vapour. There
      was a profound fall in heart rate (224+/-5 to 64+/-4 beats per min (bpm))
      associated with abnormal or absent P-waves. There were no changes in the QRS
      complex. The R-T interval (control value 118+/-4 ms) was initially shortened to
      107+/-3 ms and then prolonged to 130+/-4 ms. Heart rate and P-wave changes were
      prevented by muscarinic cholinergic blockade with methylscopolamine. The R-T
      shortening was reduced by 79+/-4% by beta-adrenergic blockade with propranolol.
      Methylscopolamine also unmasked small tachycardic responses (5-25 bpm) in 5/7
      animals. This tachycardia was prevented by propranolol. Thus both parasympathetic
      vagal cardiac nerves and sympathetic cardiac nerves are activated during the
      nasopharyngeal reflex, with increased vagal effects in the sino-atrial node, and
      increased sympathetic effects in the ventricular myocardium.

PMID- 12798207
TI  - Ionotropic glutamate receptor subunit immunoreactivity of vagal preganglionic
      neurones projecting to the rat heart.
AB  - The ionotropic glutamate receptor subunits expressed by vagal preganglionic
      neurones in the rat medulla oblongata were examined by using fluorescence
      immunolabelling combined with retrograde neuronal tracing. The general population
      of these neurones in the medulla was identified by intraperitoneal injections of
      Fluorogold and also with choline acetyltransferase antibodies. Cardiac projecting
      neurones were specifically identified by applying the fluorescent tracer 1,1'
      dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine (DiI) to the heart or by
      injecting cholera toxin B-subunit into the pericardium. Both tracers labelled
      populations of neurones lying in the dorsal vagal nucleus, intermediate reticular
      formation and nucleus ambiguus, and when both tracers were applied
      simultaneously, approximately 50% of cells were dual-labelled. Control
      experiments established that the labelling was specific for neurones projecting
      to the heart. Most vagal preganglionic neurones, including those projecting to
      the heart, irrespective of their location in the medulla, had a similar profile
      of glutamate receptor immunoreactivity. Labelling of somata for the alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic (AMPA) subunit GluR1 was weak or absent,
      while labelling with antibodies directed to GluR2, a common sequence of GluR2 and
      GluR3, and GluR4 was moderate or intense. All neurones studied appeared to
      express the N-methyl-D-aspartate (NMDA) receptor subunit NR1, and while
      antibodies recognising the NR2A and NR2B splice variants gave strong labelling,
      immunoreactivity with a NR2B specific antibody was weaker. Weak to moderate
      labelling was seen in some neurones using antibodies to the kainate receptor
      subunits KA2 and GluR5-7. These results are consistent with neurophysiological
      data indicating the presence of AMPA, NMDA and kainate responses in cardiac vagal
      preganglionic neurones, and suggest that these neurones are similar to other
      vagal parasympathetic preganglionic neurones in expressing mainly AMPA receptor
      subunits GluR2-4.

PMID- 12798208
TI  - An embryonic chick pancreas organ culture model: characterization and neural
      control of exocrine release.
AB  - An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was
      developed for use as an in vitro model to study cholinergic regulation of
      exocrine pancreatic function. The culture system was examined for characteristic
      exocrine function and viability by measuring enzyme release, and noting
      histological, morphological, and anti-amylase immuno-fluorescence staining
      changes over a series of incubation times. This embryonic culture system exhibits
      loss of viability and morphological degeneration after 12 h of incubation time.
      Characterization and development of this exocrine model system was an important
      aspect of this study. Assessment of the 18-day-old embryonic chick pancreas model
      clearly indicated biochemical and cholinergic functionality, and morphological
      integrity, of the tissue after 4-h incubation. This embryonic age and incubation
      period were utilized for all subsequent cholinergic studies. The in vitro model
      was used to study parasympathetic regulation of exocrine function via the
      muscarinc receptors present in the embryonic chick pancreas. The effects of
      synthetic muscarinic agonists (bethanechol and carbachol) and subtype-specific
      antagonists affected amylase release to varying degrees suggesting heterogeneity
      of receptors. The effects of the muscarinic receptor antagonists atropine (non
      specific), pirenzepine (M(1)-selective) and 4-DAMP [4-diphenylacetoxy-N-methyl
      piperidine methiodide] (M(3)-selective) on bethanechol-stimulated amylase release
      were examined. Atropine and 4-DAMP at concentrations of 2 microM and higher
      significantly inhibited (p<0.05) agonist-stimulated amylase release, while
      pirenzipine did not at 2 microM, but did at 200 microM. The M(3) subtype
      selective antagonist 4-DAMP (2 pM-2 mM) significantly inhibited (p<0.05) 5 mM
      bethanechol-stimulated amylase release at concentrations of 2 microM and greater
      (amylase activity decreased from 100.61 to 49.41 U/l/mg). The data suggest the
      existence of a muscarinic receptor subtype for the embryonic chick pancreas
      exocrine cells characteristic to the mammalian M(3) glandular subtype.

PMID- 12798209
TI  - Anatomic relationships of the human nucleus of the solitary tract in the medulla
      oblongata: a DiI labeling study.
AB  - The nucleus of the solitary tract (nTS) is a major site of brainstem control of
      vital functions (e.g., cardiovascular reflexes and respiration). We examined
      anatomic relationships of the human nucleus of the solitary tract, using a
      bidirectional lipophilic fluorescent tracer 1-1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI) in 10 postmortem human fetal
      midgestational medullae oblongatae. Labeling by diffusion of DiI from the nucleus
      of the solitary tract included: (1) neuropil of all future subdivisions of the
      nucleus of the solitary tract ipsilateral to the DiI crystal; (2) stellate cells
      in the caudal raphe at the junction of the nucleus raphe pallidus and the arcuate
      nucleus at the ventral medullary surface, as well as single fibers along the
      caudal raphe and the arcuate nucleus; (3) cells and fibers in other medullary
      areas related to autonomic and respiratory control, including the dorsal motor
      nucleus of the vagus, nucleus ambiguus complex/ventral respiratory group, rostral
      ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM), and
      medullary reticular formation. The pattern of connections of the nucleus of the
      solitary tract already established by midgestation in the human fetus is
      consistent with the pattern previously demonstrated in adult experimental
      animals. A major finding of the study is that of the stellate cells at the
      junction of nucleus raphe pallidus and the arcuate nucleus at the ventral
      medullary surface, which project to the nucleus of the solitary tract, and could
      be homologous to chemosensitive serotonergic neurons at the midline ventral
      medullary surface of experimental animals. This connection between the ventral
      caudal raphe and the nucleus of the solitary tract may participate in
      chemoreception and central regulation of cardiorespiratory reflexes during human
      perinatal development; it is, therefore, relevant to the study of sudden infant
      death syndrome (SIDS).

PMID- 12798210
TI  - Characterization and quantification of the return map of RR intervals by Pearson
      coefficient in patients with acute myocardial infarction.
AB  - The return map is the plot that displays the relationship between a point and its
      consecutive point in a time series. This study tried to characterize and quantify
      the return map of RR intervals (RRI) in subjects with patent coronary arteriogram
      and in patients with acute myocardial infarction (AMI) by using some parameters
      of linear regression between RRI(n+1) and RRI(n), and compared the newly
      introduced parameters with the time- and frequency-domain indices of heart rate
      variability (HRV) obtained from the same RRI. Three quantitative measures were
      introduced to quantify the return map of RRI: the Pearson coefficient, slope and
      Y-intercept of linear regression between RRI(n+1) and RRI(n). We found that the
      Pearson coefficient was almost identical to the slope of linear regression, and
      correlated significantly and negatively with Y-intercept in controls and patients
      with AMI. The Pearson coefficient and the slope in patients with AMI were
      significantly larger while the Y-intercept was significantly smaller than those
      of controls. The Pearson coefficient was also found to correlate significantly
      and negatively with the indices of vagal modulation and positively with the
      indices of sympatho-vagal balance and rennin-angiotensin-aldosterone modulation
      in both normal controls and patients with AMI. Our results suggested that the
      return map of RRI could be characterized and quantified by Pearson coefficient,
      which was related to the autonomic nervous modulation of the subject.

PMID- 12798211
TI  - Joint consultation: a joint venture towards improving effectiveness of health
      care.

PMID- 12798212
TI  - Chronic idiopathic urticaria for the generalist.
AB  - Chronic idiopathic urticaria (CIU) manifests as frequently occurring, short-lived
      wheals, surrounded by a bright-red flare, and often accompanied by angioedema.
      The cause of CIU is undefined and its diagnosis requires exclusion of other
      conditions with somewhat similar symptoms. Recent evidence has indicated that IgG
      autoantibodies directed against high-affinity IgE receptors (FcepsilonRI) may be
      involved in the pathophysiology of CIU. Following the release of mast cell or
      basophil-derived histamine, this mediator binds to H(1) and H(2) receptors,
      leading to vasodilatation and increased vascular permeability. Individuals with
      CIU may be unable to conduct normal daily activities; therefore, prompt
      initiation of effective treatment is essential. General management of patients
      should include avoidance of substances likely to trigger or intensify episodes.
      Treatment with antihistamines is the mainstay of pharmacotherapy for CIU.
      Selection of antihistamine therapy for patients with CIU should be based on the
      following key properties: (1) proven clinical efficacy in providing a high rate
      of symptom improvement, (2) rapid onset of action and a long-lasting response,
      and (3) an excellent safety profile and a high degree of tolerability. The
      benefit of some second-generation antihistamines is limited by sedation, drug
      drug interactions, or a variable therapeutic response. The H(1)-receptor
      antagonist desloratadine is a new, once-daily treatment option that is potent and
      nonsedating, and has a low potential for drug-drug interactions. Desloratadine
      has a rapid onset of action and has been shown to effectively and safely reduce
      pruritus and the number and size of hives in patients with CIU, leading to
      improvements in quality of life.

PMID- 12798213
TI  - Patients at the outpatient rheumatology clinic: do they really need to be there?
AB  - BACKGROUND: The workload at many outpatient clinics within the Dutch health care
      system has been growing relentlessly, resulting in unacceptable waiting lists and
      reduced accessibility. Assessing streams of patients and introducing a method of
      accelerated referral of patients back to the general practitioner (GP) under
      specialist guidance could help to alleviate these problems. METHODS: Seventeen
      GPs collaborated with rheumatologists during a 2-year period in a 'joint
      consultation' model in which GPs and rheumatologists discussed patients together.
      All patient charts belonging to patients who had been referred to the outpatient
      clinic by these 17 GPs were identified. Rheumatologists assessed whether or not
      these patients could be referred back to the participating GPs under the guidance
      of the specialist in the joint consultation model. RESULTS: Of 276 eligible
      patients, 121 were discharged from the outpatient clinic. Eighty-seven patients
      required specialist follow-up, 22 patients refused to participate, and six
      patients were not entered into the study by the rheumatologist. Some 21 patients
      eventually entered the study, 18 of whom were referred back to the GP.
      CONCLUSION: The role of joint consultation appears to be limited. Improving the
      referral behavior of GPs should take precedence over transferring follow-up from
      the outpatient clinic to the primary care level.

PMID- 12798214
TI  - Pulmonary functional abnormalities in asymptomatic patients with systemic
      sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a disease characterized by widespread
      fibrosis of the skin and multiple organs, including the lungs. This study was
      designed to evaluate pulmonary function in SSc patients without symptoms of lung
      involvement. METHODS: Spirometric measurements were done in 26 female SSC
      patients without symptoms of pulmonary involvement. RESULTS: Maximal voluntary
      ventilation was found to be decreased in half of the patients, and forced vital
      capacity was decreased in 23% of the patients. Forced expiratory flow rate was
      impaired in about half of the SSc patients, especially the flow at 50-75% of
      forced vital capacity. Peak expiratory flow rate was decreased in 77% of
      asymptomatic patients. CONCLUSIONS: A functional defect, mainly of the
      restrictive type, was observed in the majority of asymptomatic patients with SSc.
      Pulmonary function testing is recommended for all SSc patients.

PMID- 12798215
TI  - Exhaled nitric oxide during exercise and dobutamine stress echocardiography in
      patients with mitral stenosis.
AB  - BACKGROUND: Pulmonary hypertension (PH) is an important limiting factor of
      exercise tolerance in patients with mitral stenosis (MS). We wished to
      investigate the relationship between respiratory nitric oxide (NO), a potent
      vasodilator, and exercise tolerance in patients with moderate MS. In the same
      patients, we wondered whether acute change in pulmonary hemodynamics could affect
      respiratory NO. METHODS: Ten patients with moderate MS (valve area 1.4+/-0.2
      cm(2)) were studied at rest, during incremental cycle ergometry exercise, and
      during dobutamine stress echocardiography (DSE). The concentration of NO in
      exhaled air (FE(NO)) and NO output (V'(NO)) were measured at baseline, at the end
      of exercise, and at the end of DSE. Eight healthy subjects served as normal
      controls for NO output during exercise. RESULTS: During exercise, FE(NO)
      decreased both in patients and in controls, while V'(NO) increased in both. At
      the end of exercise, both VO(2) max and V'(NO) were significantly higher in
      controls than in patients. The increase in V'(NO) during exercise was
      significantly correlated with VO(2) max, both in patients and in controls. During
      DSE, cardiac output (CO), pulmonary artery pressure (PAP), and mitral valve
      gradient increased. No changes in mean FE(NO), V'(NO), or ventilation were
      observed during DSE. There was a significant inverse correlation between FE(NO)
      and mitral valve gradient at the end of DSE. CONCLUSIONS: In patients with
      moderate MS, exercise performance is correlated with respiratory NO output. In
      the same patients, during DSE, the increase in CO, which is not accompanied by an
      increase in ventilation, is not associated with an increase in respiratory
      V'(NO).

PMID- 12798216
TI  - A new serum assay to measure N-terminal fragment of telopeptide of type I
      collagen in patients with renal osteodystrophy.
AB  - BACKGROUND: Up until now, there was little known about the use of bone resorption
      markers in the assessment of bone status in patients with chronic renal failure
      (CRF). The present study evaluated the ability of a new immunoassay for N
      terminal telopeptide of type I collagen to assess bone turnover in a group of
      hemodialyzed patients. METHODS: The following parameters were measured in a
      fasting blood sample from 111 patients on maintenance hemodialysis for at least 2
      years and in 120 healthy subjects: calcium, phosphorus, magnesium, BALP, PTH, and
      N-terminal telopeptide of type I collagen (NTx-ELISA, OSTEOMARK NTx Siero-Ostex
      International). RESULTS: Serum PTH, BALP, and NTx were significantly higher
      (P<0.001) in hemodialyzed (HD) patients than in healthy subjects. In HD patients,
      PTH was correlated to BALP and NTx (r=0.40 and 0.55, respectively). When
      combining PTH and BALP serum levels, 17 patients showed high turnover (HT) and 65
      were found to have a normal to low turnover (N-LT). In HT patients, serum NTx and
      dialytic age were significantly (P<0.01) higher than in N-LT patients. Moreover,
      even after adjusting for age, body mass index, dialytic age, and calcium-vitamin
      D treatment, serum NTx discriminated between HT and N-LT with a sensitivity of
      97.6% and a specificity of 90.9%. CONCLUSION: Although bone biopsy remains the
      reference method for the diagnosis of renal osteodystrophy, the combined use of
      markers of bone resorption and bone formation could improve the clinical
      management of renal bone diseases.

PMID- 12798217
TI  - Interrelationship of smoking, paraoxonase activity, and leisure time physical
      activity: a population-based study.
AB  - METHODS: We determined the effect of smoking on PON1 activity levels in a
      population-based sample of 1380 subjects and examined the possibility of regular
      physical activity modulating the effect of cigarette smoking on PON1 activity
      levels at a population level. RESULTS: Mean PON1 activity was significantly lower
      in smokers than in non- or ex-smokers (237.6+/-8.4 vs. 276.7+/-5.3 U/l, mean+/
      S.E.M.; P= 0.001). PON1 activity levels were significantly higher in physically
      active subjects than in those who were inactive (296.1+/-10.4 vs. 260.1+/-9.2
      U/l; P=0.002). Inactive smokers showed significantly lower PON1 activity levels
      than inactive nonsmokers (P=0.002). These differences disappeared when active
      nonsmokers were compared with active smokers. Serum PON1 activity levels were
      found to be significantly increased in active smokers compared to those in
      inactive smokers. A statistically significant interaction (P=0.003) between
      smoking and physical activity on PON1 activity was observed. CONCLUSION: Smoking
      appears to have a deleterious effect on PON1 activity levels. Being physically
      active clearly attenuates this effect.

PMID- 12798218
TI  - Correlation between daily cyclosporine dose and allograft injury in liver
      recipients with and without recurrent hepatitis C.
AB  - BACKGROUND: After liver transplantation, the daily cyclosporine dose is adjusted
      to maintain the blood level in a chosen range. The aim of this study was to
      assess the influence of liver graft injury on cyclosporine dose. METHODS: The
      parameters of liver function were investigated in 145 patients. Ninety-two
      patients took part in a longitudinal study. RESULTS: The cyclosporine dose
      correlated with the MEGX test (r=0.38, P=0.01) and with the ICG (r=0.38,
      P=0.0001) and BSP (r=0.37, P=0.0002) clearances; it had an inverse correlation
      with transaminases (AST: r=0.38, P=0.0001) and histological lesions (r=-0.29,
      P=0.005). The cyclosporine dose was lower in patients with recurrent hepatitis C
      (179+/-9 mg/day) than in those without (241+/-10 mg/day), and was lower in
      patients with chronic hepatitis (154+/-9 mg/day) than in those without (207+/-16
      mg/day). In the longitudinal study, the percent variation of AST correlated
      inversely with that of cyclosporine dose (r=-0.62, P=0.0002). CONCLUSION:
      Progressive graft injury leads to a reduction in the cyclosporine dose,
      particularly in patients with recurrent hepatitis C.

PMID- 12798219
TI  - Intrahepatic cholestasis and pure red cell aplasia associated with ticlopidine.
AB  - A 77-year-old woman developed jaundice and anemia 3 and 8 weeks, respectively,
      after starting ticlopidine (100 mg daily) for cerebral infarction. From the
      laboratory findings, including histological study of the liver and bone marrow
      specimen, ticlopidine-induced intrahepatic cholestasis and pure red cell aplasia
      were highly suspected. Jaundice slowly improved after the withdrawal of
      ticlopidine. Anemia immediately improved with steroid therapy. These are very
      rare adverse effects of ticlopidine; nevertheless, periodic laboratory
      examinations are recommended.

PMID- 12798220
TI  - Bilateral fractured neck of the femur in an adult patient with cystic fibrosis.
AB  - A 34-year-old man with cystic fibrosis (CF) sustained a bilateral fractured neck
      of the femur during the course of six grand mal seizures. The fractures were
      successfully treated with bipolar hemi-arthroplasties. Several risk factors for
      osteoporosis were present. Bone pathology showed reduced femoral head bone
      density. Osteoporosis of the lumbar spine was confirmed by dual-energy X-ray
      absorptiometry. As the life expectancy of patients with CF continues to improve,
      osteoporosis and its sequelae will become more common. We should be aware of the
      increased risk of bilateral fractured neck of the femur following epileptic
      seizure in CF.

PMID- 12798221
TI  - Hyperferritinemia revealing Gaucher's disease.
AB  - Hyperferritinemia is frequently observed during Gaucher's disease but has never
      been described as an initial manifestation. We report the case of a 57-year-old
      woman without a previous medical history who presented with hyperferritinemia and
      IgG monoclonal gammopathy. The diagnostic procedure was negative except for the
      bone marrow biopsy, which revealed Gaucher's cells. Low beta-glucocerebrosidase
      activity in leukocytes confirmed the diagnosis of adult Gaucher's disease. We
      discuss the differential diagnosis and the mechanisms of hyperferritinemia in
      this disease.

PMID- 12798222
TI  - Hypoparathyroidism preceding Riedel's thyroiditis.
AB  - We report the case of a woman who presented with primary hypoparathyroidism and
      who subsequently developed extensive Riedel's thyroiditis. To our knowledge, this
      is the first reported case of primary hypoparathyroidism preceding Riedel's
      thyroiditis. This observation suggests that Riedel's thyroiditis is part of a
      diffuse fibrotic process that may involve other organs, such as the parathyroid
      glands.

PMID- 12798223
TI  - Internal medicine: yesterday, today, and tomorrow. Part I. Origin and
      development: the historical perspective.

PMID- 12798224
TI  - Acute epididymitis and septicemia due to Streptococcus equisimilis.

PMID- 12798225
TI  - An economic comparison of ill-defined diagnostic problems in internal medicine
      and uncomplicated normal vaginal delivery.

PMID- 12798226
TI  - Do viruses form lineages across different domains of life?
AB  - The scarce characterisation of the viral world has hampered our efforts to
      appreciate the magnitude and diversity of the viral domain. It appears that
      almost every species can be infected by a number of viruses. As our knowledge of
      viruses increases, it appears that this myriad of viruses may be organised into a
      reasonably low number of viral lineages including members infecting hosts
      belonging to different domains of life. Viruses belonging to a lineage share a
      common innate "self" that refers to structural and assembly principles of the
      virion. This hypothesis has a few consequences. All viruses are old, maybe
      preceding cellular life, and virus origins are polyphyletic, as opposed to the
      idea of a monophyletic origin of cellular life.

PMID- 12798227
TI  - The role played by viruses in the evolution of their hosts: a view based on
      informational protein phylogenies.
AB  - Viruses are often considered as fragments of cellular RNA or DNA that escaped a
      long time ago from cellular chromosomes and that evolved later on by capturing
      additional genes from the genomes of their hosts. However, this view has now been
      challenged by the discovery of surprising homology between viruses with very
      distantly related hosts, and by phylogenetic analyses suggesting that genes might
      also have flown from viruses to cells. We present here phylogenetic analyses of
      four proteins involved in DNA replication and synthesis of DNA precursors (DNA
      polymerases delta, ribonucleotide reductases, thymidylate synthases and
      replicative helicases) and we discuss the reciprocal roles of cells and viruses
      during the evolutionary history of these enzymes. These analyses revealed
      numerous lateral gene transfer events between cells and viruses, in both
      directions. We suggest that lateral gene transfers from viruses to cells and
      nonorthologous gene replacements of cellular genes by viral ones are an important
      source of "genetic novelties" in the evolution of cellular lineages. Thus,
      viruses have definitively to be considered as major players in the evolution of
      cellular genomes.

PMID- 12798228
TI  - Bacteriophage observations and evolution.
AB  - Bacteriophages are classified into one order and 13 families. Over 5100 phages
      have been examined in the electron microscope since 1959. At least 4950 phages
      (96%) are tailed. They constitute the order Caudovirales and three families.
      Siphoviridae or phages with long, noncontractile tails predominate (61% of tailed
      phages). Polyhedral, filamentous, and pleomorphic phages comprise less than 4% of
      bacterial viruses. Bacteriophages occur in over 140 bacterial or archaeal genera.
      Their distribution reflects their origin and bacterial phylogeny. Bacteriophages
      are polyphyletic, arose repeatedly in different hosts, and constitute 11 lines of
      descent. Tailed phages appear as monophyletic and as the oldest known virus
      group.

PMID- 12798229
TI  - Bacteriophages with tails: chasing their origins and evolution.
AB  - Comparative genomic analysis of the tailed bacteriophages shows that they are
      genetically mosaic with respect to each other, implying that horizontal exchange
      of sequences is an important component of their evolution. Horizontal exchange
      occurs intensively among closely related phages but also at reduced frequency
      across the entire population of tailed phages. It results in exchange of
      homologous functions, exchange of analogous but non-homologous functions as with
      the prophage integrases, and introduction of novel functions into the genome as
      with the morons. Extrapolation of these processes back in evolutionary time leads
      to a speculative model for the origins and early evolution of phages.

PMID- 12798230
TI  - The diversity and evolution of the T4-type bacteriophages.
AB  - Recent studies suggest that viruses are the most numerous entities in the
      biosphere; bacteriophages, the viruses that infect Eubacteria and Archaea,
      constitute a substantial fraction of this population. In spite of their ubiquity,
      the vast majority of phages in the environment have never been studied and
      nothing is known about them. For the last 10 years our research has focused on an
      extremely widespread group of phages, the T4-type. It has now become evident that
      phage T4 has a myriad of relatives in nature that differ significantly in their
      host range. The genomes of all these phages have homology to the T4 genes that
      determine virion morphology. Although phylogenetically related, these T4-type
      phages can be subdivided into four groups that are increasingly distant from T4:
      the T-evens, the pseudo T-evens, the schizo T-evens and the exo T-evens. Genomic
      comparisons between the various T4-type phages and T4 indicate that these genomes
      share homology not only for virion structural components but also for most of the
      essential genes involved in the T4 life cycle. This suggests that horizontal
      transmission of the genetic information may have played a less general role in
      the evolution of these phages than has been supposed. Nevertheless, we have
      identified several regions of the T4-type genome, such as the segment containing
      the tail fiber genes that exhibit evidence of extensive modular shuffling during
      evolution. The T4-type genomes appear to be a mosaic containing a large and fixed
      group of essential genes as well as highly variable set of non-essential genes.
      These non-essential genes are probably important for the adaptation of these
      phages to their particular life-style. Furthermore, swapping autonomous domains
      within the essential proteins may slightly modify their function(s) and
      contribute to the adaptive ability of the T4-type phage family. Regulatory
      sequences also display considerable evolutionary plasticity and this too may
      facilitate the adaptation of phage gene expression to new environments and
      stresses.

PMID- 12798232
TI  - Prophage insertion sites.
AB  - Insertion of viral DNA into host chromosomes is an ancient process essential for
      propagation in the proviral form. Many present-day bacteriophages insert at
      specific sites on the host chromosome. Insertion by two coliphage families
      (lambdoid and P4-like) is compared. For both families, insertion sites frequently
      lie within tRNA genes. The lambdoid phages insert at anticodon loops, whereas the
      p4-like phages insert in the TpsiC loops downstream from them. The association of
      both groups with tRNA genes suggests that the primordial insertion site of both
      groups may have been within a tRNA gene. The integrase proteins used in phage
      insertion may have originated at that stage, with subsequent diversification of
      specificity.

PMID- 12798231
TI  - Myoviridae bacteriophages of Pseudomonas aeruginosa: a long and complex
      evolutionary pathway.
AB  - Recently we have accomplished the entire DNA sequence of bacteriophage phiKZ, a
      giant virus infecting Pseudomonas aeruginosa. The 280334-bp of phiKZ genome is a
      linear, circularly permutated and terminally redundant, AT-rich dsDNA molecule
      that contains no sites for NotI, PstI, SacI, SmaI, XhoI and XmaIII endonucleases.
      Limited homology to other bacteriophages on the DNA and protein levels indicated
      that phiKZ represents a distinct branch of the Myoviridae family. In this work,
      we analyzed a group of six P. aeruginosa phages (Lin68, Lin21, PTB80, NN, EL, and
      RU), which are morphologically similar to phiKZ, have similar genome size and low
      G+C content. All phages have a broad host range among P. aeruginosa strains, and
      they are resistant to the inhibitory action of many P. aeruginosa plasmids. The
      analysis of the genomic DNA by restriction enzymes and DNA-DNA hybridization
      shows that phages are representative of three phiKZ-like species: phiKZ-type
      (phiKZ, Lin21, NN and PTB80), EL-type (EL and RU) and Lin68 which has a shorter
      tail than other phages. Except for related phages EL and RU, all phiKZ-like
      phages have identical N-terminal amino acid sequences of the major capsid
      protein. Random genome sequencing shows that the EL and RU phages have no
      homology to the phiKZ-like phages on DNA level. We propose that the phiKZ, Lin21,
      NN, PTB80 and Lin68 phages can be included in a new phiKZ genus, and that the EL
      and RU phages belong to a separate genus within the Myoviridae family. Based on
      the resistance to many restriction enzymes and the transduction ability, there
      are indications that over the long pathway of evolution, the phiKZ-like phages
      probably inherited the capacity to infect different bacterial species.

PMID- 12798234
TI  - Evolutionary insights from studies on viruses of hyperthermophilic archaea.
AB  - The morphological diversity of viruses which parasitize hyperthermophilic archaea
      thriving at temperatures > or = 80 degrees C appears to exceed that of viruses of
      prokaryotes living at lower temperatures. Based on assumptions of the existence
      of viruses in the prebiotic phase of evolution and hot origins of cellular life,
      we suggest that this remarkable diversity could have its source in ancestral
      diversity of viral morphotypes in hot environments. Attempts are made to trace
      evolutionary relationships of viruses of hyperthermophilic archaea with other
      viruses.

PMID- 12798233
TI  - Channeling phage DNA through membranes: from in vivo to in vitro.
AB  - We discuss current models of phage DNA transport through membranes. We present
      results that attempt to answer the following questions: is there a single
      mechanism of transport for all types of phage? is DNA transported as a free
      molecule or in association with proteins? what is the driving force for
      transport?

PMID- 12798235
TI  - Relationships between fuselloviruses infecting the extremely thermophilic
      archaeon Sulfolobus: SSV1 and SSV2.
AB  - The fusellovirus SSV2 from an Icelandic Sulfolobus strain was isolated,
      characterized and its complete genomic sequence determined. SSV2 is very similar
      in morphology, replication, genome size and number of open reading frames (ORFs)
      to the type virus of the family, SSV1 from Japan, except in its high level of
      uninduced virus production. The nucleotide sequences are, however, only 55%
      identical to each other, much less than related bacteriophage, related animal
      viruses and the rudiviruses of Sulfolobus, SIRV1 and SIRV2. Nevertheless the
      genome architecture is very similar between the two viruses, indicating that
      despite this genomic dissimilarity the virus genomes are mostly homologous.
      Unlike SSV1, the sequence of SSV2 indicates integration into a glycyl tRNA gene
      and is completely missing a DNA packaging gene. There is a unique, perfectly
      tandemly directly repeated sequence of 62 nucleotides in SSV2 that has no
      similarity to known sequences or structures. By comparison to the SSV2 genome, an
      integrated partial fusellovirus genome was found in the Sulfolobus solfataricus
      P2 genome further confirming the dynamism of the Sulfolobus genome. Clustering of
      cysteine codon containing ORFs both in SSV1 and SSV2 indicates that these
      Fuselloviridae arose from a genome fusion event.

PMID- 12798236
TI  - Observation of virus-like particles in high temperature enrichment cultures from
      deep-sea hydrothermal vents.
AB  - A systematic search was carried out on samples collected in various
      geographically distant hydrothermal sites located on the East Pacific Rise (EPR 9
      degrees N and 13 degrees N) and Mid-Atlantic Ridge (MAR 36 degrees N and 37
      degrees N) to investigate the diversity of virus-like particles (VLPs) from deep
      sea vents. Eighty-nine positive enrichment cultures were obtained from one
      hundred and one crude samples at 85 degrees C. VLPs were detected by electron
      microscopy in fifteen different enrichments. Among the different morphotypes
      observed, the lemon-shaped type prevailed but rods and novel pleomorphic
      morphologies were also observed. Several observations strongly suggested that
      host strains of the novel VLPs belong to the hyperthermophilic euryarchaeal order
      Thermococcales.

PMID- 12798237
TI  - Haloarchaeal viruses: how diverse are they?
AB  - Hypersaline lakes are highly productive microbial environments that provide many
      advantages for microbial ecologists, including stable communities of relatively
      low diversity (mainly haloarchaea). An important component of these communities
      is comprised of their non-cellular parasites, i.e., their viruses. Few viruses of
      halobacteria (haloviruses) have been isolated and studied even though a wide
      selection of host species have been formally described (and easily cultured) for
      ten years. Hypersaline waters have been shown to contain very high concentrations
      of virus-like particles (at least 10(7) particles/ml), particularly fusiform
      particles, but laboratory isolations of new haloviruses have been very slow and
      the detailed study of selected examples even slower. Here we provide an outline
      of the reported haloviruses, including fusiform and unpublished isolates from
      this laboratory, and we discuss their diversity and the future directions for
      this research.

PMID- 12798238
TI  - Development of a rapid method using nucleic acid sequence-based amplification for
      the detection of astrovirus.
AB  - We have developed a rapid method to detect astrovirus in fecal specimens
      utilizing nucleic acid sequence-based amplification (NASBA) and several detection
      methodologies, including a sandwich hybridization assay based on DNA-tagged
      liposomes (liposome-strip detection assay). RNA was extracted from 65 stool
      specimens that were positive for astrovirus by enzyme immunoassay and was
      amplified by both NASBA and reverse transcriptase PCR (RT-PCR). Also extracted
      and amplified were 19 specimens containing rotavirus, 20 specimens containing
      norovirus, five specimens containing adenovirus, 15 water negative control
      specimens, and eight specimens containing astrovirus reference strains. NASBA
      products were detected by electrochemiluminescence detection (ECL) and by
      liposome-strip detection; RT-PCR products were detected by ethidium bromide
      staining following gel electrophoresis and by liquid hybridization assay (LHA).
      There was no significant difference in the detection rates of NASBA- and RT-PCR
      based assays, with one exception in which the NASBA/ECL assay detected astrovirus
      in eight specimens that tested negative by the RT-PCR/LHA assay. These results
      suggest that these NASBA-based detection methods have detection rates that are as
      good as or better than those of RT-PCR-based methods. Both NASBA and liposome
      strip detection may be useful for field studies and environmental testing because
      these methods are rapid and do not require specialized equipment.

PMID- 12798239
TI  - Improved detection of cutaneous human papillomavirus DNA by single tube nested
      'hanging droplet' PCR.
AB  - A single tube nested 'hanging droplet' PCR was developed for detection of
      cutaneous human papillomavirus (HPV) DNA of the phylogenetic group B1. The nested
      PCR was compared with a single round PCR method by testing 56 fresh biopsies from
      Australian skin tumour patients. HPV DNA was detected in 64% (36/56) of the
      biopsies by nested PCR and in 30% (17/56) by single round PCR (P<0.001). HPV DNA
      was more often detected by nested PCR than by single round PCR in basal cell
      carcinoma [62% (16/26) vs. 19%; (5/26); P=0.003], squamous cell carcinoma [43%
      (7/16) vs. 25% (4/16)] and in solar keratosis [93% (13/14) vs. 57% (8/14);
      P=0.038]. The nested PCR and the single round PCR system detected 26 and 11
      different HPV types/putative types/subtypes, respectively. Multiple types were
      found in eight samples by the nested PCR and two samples by single round PCR. The
      nested HPV PCR is more sensitive and capable of amplifying a broad spectrum of
      HPV types from skin tumours, but further improvements are needed before all HPV
      infections in skin can be detected by a single assay.

PMID- 12798240
TI  - Half-genome human immunodeficiency virus type 1 constructs for rapid production
      of reporter viruses.
AB  - The use of reporter constructs of HIV-1 molecular clones has been useful in
      studying the effects of infection on individual cells. A strategy of producing
      viral half-genome constructs containing reporter genes that can be used to
      produce recombinant complete infectious virions is described. This approach
      allows rapid generation of reporter and non-reporter virions from the same
      genetic construct, obviating the need to produce a new reporter genetic construct
      for each viral change to be studied. We provide an example of the utility of this
      system for studying the effects of Nef on infected cells.

PMID- 12798241
TI  - Experimental layout, data analysis, and thresholds in ELISA testing of maize for
      aphid-borne viruses.
AB  - Several aspects of enzyme-linked immunosorbent assay (ELISA) procedures and data
      analysis have been examined in an attempt to find a rapid and reliable method for
      discriminating between 'positive' and 'negative' results when testing a large
      number of samples. A layout of ELISA plates was designed to reduce uncontrolled
      variation and to optimize the number of negative and positive controls. A
      transformation using the fourth root (A(1/4)) of the optical density readings
      corrected for the blank (A) stabilized the variance of most ELISA data examined.
      Transformed A values were used to calculate the true limits, at a set protection
      level, for false positive (C) and false negative (D). Methods are discussed to
      reduce the number of undifferentiated samples, i.e. the samples with response
      falling between C and D. The whole procedure was set up for use with an
      electronic spreadsheet. With the addition of few instructions of the type 'if em
      leader then em leader else' in the spreadsheet, the ELISA results were obtained
      in the simple trichotomous form 'negative/undefined/positive'. This allowed rapid
      analysis of more than 1100 maize samples testing for the presence of seven aphid
      borne viruses-in fact almost 8000 ELISA samples.

PMID- 12798242
TI  - Multiplex RT-PCR-ELISA compared with bioassay for the detection of four apple
      viruses.
AB  - A sensitive and reliable multiplex RT-PCR-ELISA technique for the detection of
      Apple chlorotic leaf spot virus, Apple stem pitting virus, Apple mosaic virus and
      Apple stem grooving virus was developed. This technique is compared with the
      method used commonly for indexing by woody indicators, which is time consuming
      and expensive. For the RT-PCR-ELISA technique, the amplified products were
      labeled with digoxigenin during the RT-PCR by incorporation of a digoxigenin
      labeled primer. After hybridization of the PCR products to specific capture
      oligonucleotides, which were bound covalently to the surface of NucleoLink
      strips, anti-digoxigenin antibodies were used for detection. More than 100
      samples were tested in parallel by indexing and multiplex-RT-PCR-ELISA. All
      infections detected by woody indicators were also detected by multiplex RT-PCR
      ELISA. Furthermore, additional infections were only found by multiplex RT-PCR
      ELISA. The colourimetric detection of multiplex-RT-PCR products was at least as
      sensitive and sometimes slightly more sensitive than detection by gel
      electrophoresis. The results show that this molecular technique is more reliable
      for the detection of the above mentioned apple viruses than indexing by woody
      indicators, thereby helping to reduce cost and time during the certification of
      plant material.

PMID- 12798243
TI  - Quantitation of antibody-bound and unbound Sin Nombre virus in the plasma of
      patient with hantavirus pulmonary syndrome.
AB  - Hantavirus pulmonary syndrome (HPS) is a rare but acute fulminant disease caused
      by Sin Nombre virus and other related hantaviruses. We reported earlier that HPS
      patients had high levels of viremia and the levels of viremia correlated with the
      severity of the disease. To determine whether the viruses are free in plasma or
      bound to antibodies to form immune complexes, we established a method to
      quantitate viral genomic RNA in antibody-bound viruses and in unbound viruses
      separately. To isolate immune complexes from plasma we used protein L, which
      binds to all classes of immunoglobulins and all subclasses of IgG, and we
      measured viral RNA copy number in antibody-bound viruses and unbound viruses by
      quantitative RT-PCR. We analyzed plasma samples collected on admission from 15
      patients with HPS in the acute phase. The percentage of viral RNA in immune
      complexes versus total viral RNA varied from 9 to 91% among patients, and
      correlated with the total viral RNA copy numbers (P<0.05) and the neutralizing
      antibody titers of plasma (P<0.05). This quantitative method may be useful to
      examine diseases where immune complex formation or antibody-dependent enhancement
      may be involved in pathogenesis.

PMID- 12798244
TI  - Application of short monolithic columns for improved detection of viruses.
AB  - Monolithic chromatography media represent a novel generation of stationary phases
      introduced in the last 10-15 years providing a chromatography matrix with
      enhanced mass transfer and hydrodynamic properties. These features allow for an
      efficient and fast separation of especially large biomolecules like e.g., DNA and
      viruses. In this study, the enrichment of virus RNA on short monolithic columns
      prior to molecular detection of viruses is described. Measles and mumps viruses
      were chosen as model viruses. The results show that it is possible to bind viral
      RNA on monoliths and concentrate viral nucleic acids from a fairly dilute sample.
      Consequently, a potential application of short monolithic columns is the
      concentration of virus RNA to improve the sensitivity and selectivity of viral
      detection with the possibility of isolating viral RNA from cell-free biological
      fluids.

PMID- 12798245
TI  - Capturing ion exchanger-bound infectious pancreatic necrosis virus--design and
      application for large volume water samples.
AB  - A method was designed for rapid and reliable demonstration of the presence of
      infectious pancreatic necrosis virus retrieved from 5 l water samples. Viruses
      together with an added carrier protein were adsorbed to a resin of an added anion
      exchanger. Then the resin was collected rapidly and quantitatively through a
      specific device which we designed. The resin was transferred to a column from
      which the viruses were eluted, and subsequently further concentrated by acid
      precipitation, followed by SDS-polyacrylamide gel electrophoresis and Western
      blot analysis. Serological results were obtained within 24 h after the water
      sample was introduced into the laboratory. Proteins were recovered at an
      efficiency between 70 and 80% and the total concentration factor ranged between
      150000 and 250000 times, depending on the requirements and the methods of choice.

PMID- 12798246
TI  - MAC-ELISA and ELISA inhibition methods for detection of antibodies after yellow
      fever vaccination.
AB  - The IgM antibody capture ELISA (MAC-ELISA) and ELISA inhibition methods for the
      detection of antibodies against dengue virus were modified to detect antibodies
      against yellow fever virus. Tests were carried out in 21 persons vaccinated with
      17D and compared with the Plaque reduction neutralizing test. Of 17 naive
      subjects vaccinated, 16 (94%) seroconverted using the MAC-ELISA test and 14 (82%)
      seroconverted (or >/=fourfold titer increase) in the ELISA inhibition method.
      Cross-reactivity was evaluated by both tests and resulted in a high specificity
      to IgM antibodies against yellow fever, when all the samples from vaccinated
      individuals were negative by MAC-ELISA using dengue antigen. However, 10.7% of
      the positive dengue sera from the Santiago de Cuba epidemic cross-reacted by MAC
      ELISA using yellow fever antigen. ELISA inhibition method showed high cross
      reactivity when the 21 sera pairs were worked with yellow fever and dengue
      antigens. The MAC-ELISA and ELISA inhibition methods have become indispensable
      tools in our laboratory in order to maintain a surveillance system for dengue and
      dengue hemorrhagic fever. They are relatively rapid, simple, and they do not
      require sophisticated equipment. Both MAC-ELISA and ELISA inhibition methods for
      yellow fever could be useful for diagnosis, surveillance and yellow fever vaccine
      evaluation.

PMID- 12798247
TI  - Detection of yellow fever virus: a comparison of quantitative real-time PCR and
      plaque assay.
AB  - Yellow fever virus quantitation is performed routinely by cultivation of virus
      containing samples using susceptible cells. Counting of the resulting plaques
      provides a marker for the number of infectious particles present in the sample.
      This assay usually takes up to 5 days before results are obtained and must be
      carried out under L2 or L3 laboratory conditions, depending on the yellow fever
      virus strain used. For clinical diagnosis of yellow fever virus infections the
      cell culture-based approach takes too long and is of limited practical relevance.
      Recently, due to its considerable sensitivity, PCR has become a promising method
      for virus detection. However, whilst PCR can detect virus-specific nucleic acids,
      it does not allow conclusions to be drawn regarding the infectious potential of
      the virus detected. Nonetheless, for diagnostic purposes, a rapid, specific and
      sensitive virus PCR is preferable. Therefore, two independent yellow fever virus
      specific real-time PCR assays were established and compared the viral RNA loads
      to the results of a traditional plaque assay. The estimated ratio of yellow fever
      virus genomes to infectious particles was between 1000:1 and 5000:1; both
      approaches displayed a comparable precision of <45%. A significant correlation
      between genome number as determined by real-time PCR and the corresponding number
      of plaques in paired samples was found with a Pearson coefficient of correlation
      of r=0.88 (P<0.0001).

PMID- 12798248
TI  - Direct extraction of Sabin poliovirus genomes from human fecal samples using a
      guanidine thiocyanate extraction method.
AB  - To permit rapid and efficient detection of Sabin poliovirus type 3 from human
      fecal samples, we developed a guanidine thiocyanate (GuSCN) extraction and
      reverse transcriptase polymerase chain reaction (RT-PCR) method. Using 10-fold
      serial dilutions from stock Sabin-Leon 12 a1b poliovirus type 3 at 10(7) TCID(50)
      per 0.1 ml, genome was detected to a dilution of 10(3) TCID(50) per 0.1 ml. A
      total of 40 archived fecal samples were examined using this GuSCN extraction
      method followed by RT-PCR. Fourteen of 20 poliovirus type 3 tissue culture
      positive specimens (70%) and two of 20 tissue culture-negative specimens (10%)
      were detected by GuSCN extraction and RT-PCR. All positive and negative
      extraction and RT-PCR controls were identified accurately. This GuSCN extraction
      and RT-PCR technique is rapid, inexpensive, and can be readily adapted to
      identify genome sequences of other enterovirus types in large numbers of fecal
      samples. Moreover, the GuSCN technique extracts viral RNA directly from fecal
      samples, allowing observation of in vivo alterations of genome sequences. Further
      studies are underway to examine the development of revertant point mutations in
      the Sabin poliovirus type 3 genome following oral administration of trivalent
      Sabin Oral Poliovirus Vaccine to humans.

PMID- 12798250
TI  - Early experience and depressive disorders: human and non-human primate studies.
AB  - This paper reviews evidence from both human and non-human primate studies
      concerning the role of early adverse experiences in the onset and course of adult
      depressive disorders. Despite accumulating evidence that stressful life events
      can play a major role in precipitating the onset of depressive episodes in
      humans, the mechanisms by which early experiences mediate and moderate the risk
      for later affective illnesses are not fully understood. Experimental paradigms in
      primates have documented the important role of undeveloped (social deprivation)
      or disrupted attachment systems (social separation). Effects of early social
      deprivation can be seen in many domains. Behavioral effects include repetitive
      idiosyncratic behaviors, increased self-directed behaviors, inappropriate
      expression of aggressive behaviors, non-modulated patterns of consumption, and
      inappropriate sexual and maternal behaviors. Cognitively, such animals require
      longer habituation time for any task and demonstrate increased perseverance on
      tasks following non-reward. Physiological effects include an altered hypothalamic
      pituitary-adrenal response to stress, changes in diurnal temperature regulation,
      and alterations in immune function. Neurochemical effects include abnormalities
      in noradrenergic, serotonergic, and dopaminergic systems. Even neuroanatomical
      changes following early social deprivation have been reported. Studies with
      primates have also confirmed that early maternal and peer separations are major
      behavioral and neurobiological events with both short- and long-term consequences
      that parallel human depression. Future utilization of experimental paradigms in
      non-human primates may assist in better understanding the role of early
      experiences in predisposing to the development of affective illnesses in humans.
      This review concludes by presenting a model for understanding a developmentally
      based vulnerability to adult depressions.

PMID- 12798249
TI  - A replicon-based bioassay for the measurement of interferons in patients with
      chronic hepatitis C.
AB  - Overall treatment results of chronic hepatitis C have improved markedly with the
      introduction of pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin
      combination therapy. However, cure rates in the most common genotype 1 infection
      are still unsatisfactory. IFN-alpha dose-response studies on viral kinetics
      suggest that inadequate dosing might be a key factor but drug levels have hardly
      been tested, which is in part due to difficulties in measuring this cytokine in
      patient samples. We have shown recently that hepatitis C virus (HCV) replicons
      are highly sensitive to IFN-alpha. In this report we tested whether the replicon
      system could be used as a sensitive bioassay to determine the amount of
      biologically active IFN-alpha in serum or heparinized plasma of patients under
      therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA
      was developed that carries the gene encoding the firefly luciferase. Dose
      response studies with IFN-alpha demonstrate that the amount of expressed
      luciferase directly correlates with the level of HCV replication. By using this
      cell-based assay, serum samples of HCV patients treated with different types and
      doses of IFN-alpha were analyzed in parallel to IFN-alpha standards made by
      serial dilutions of the same type of IFN-alpha the patient was treated with.
      Based on nonlinear logistic models serum concentrations corresponding to 1.3-19
      U/ml were determined in patients under standard or high dose IFN-alpha therapy,
      and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-alpha. In conclusion,
      the HCV-replicon based bioassay allows determining the levels of biologically
      active IFN-alpha in serum and heparinized plasma of patients under treatment.

PMID- 12798251
TI  - How accurate are patients in reporting their antidepressant treatment history?
AB  - BACKGROUND: A patient's report of their antidepressant treatment history is one
      of the most important pieces of information used in selecting an antidepressant
      regimen. It is currently unknown how accurate patients are in describing and
      characterizing their antidepressant treatment history. METHODS: Seventy-three
      patients receiving treatment for depression at our outpatient psychiatric
      practice were interviewed by an independent evaluator who was blind to each
      patient's treatment history. Information was obtained regarding which
      antidepressant and augmentation regimens patients had undergone, antidepressant
      doses, duration of trials, and the nature of response to each trial. The results
      of these interviews were then compared with patients' actual treatment history as
      elicited from an independent chart review. RESULTS: Patients recalled 85 of the
      104 (81.7%) monotherapy trials they had undergone in the past 5 years, but only
      recalled 12 of 46 (26.1%) augmentation trials (P<0.001). Patients were found to
      be very reliable in distinguishing between those trials that were of adequate
      dose and duration and those that were not. Patients were also generally reliable
      in depicting the quality of response to past trials, though patient report of a
      past negative trial was significantly more reliable than a report of a past
      positive trial. The presence of current depressive symptomatology did not
      adversely affect patients' ability to recall past trials or accurately describe
      their responses to past regimens. LIMITATIONS: All patients were treated by a
      single psychiatrist, and all trials occurred within the last 5 years. CONCLUSION:
      Patients are able to recall the majority of monotherapy trials they have
      undergone, but have great difficulty remembering when two medications were taken
      concurrently, i.e. augmentation trials. Patient report appears to be a
      satisfactory method to obtain information regarding trial adequacy and response
      in most, but not all instances.

PMID- 12798253
TI  - Self, friends, and lovers: structural relations among Beck Depression Inventory
      scores and perceived mate values.
AB  - BACKGROUND: We used an economic model based on evolutionary theory to guide an
      examination of relations among self-reported depressive symptoms and ratings of
      mate values of self, social, and sexual partners. This model treats assortative
      mating as a form of social exchange between partners of socially and sexually
      desirable traits. METHODS: Two studies used variants of the Mate Value Inventory
      (MVI), a multivariate assessment of attributes desired in social or sexual
      partners. For study 1, 115 male and 124 female undergraduates provided self
      reports on four forms of the MVI-11 and on the Beck Depression Inventory (BDI);
      for study 2, 208 male and 277 female undergraduates provided self reports on
      seven forms of the MVI-7 and on the BDI-II. RESULTS: Both multisample structural
      equations models indicated that the parameters were statistically equivalent
      between female and male subsamples and provided an adequate fit to the data. The
      models revealed significant relations between the mate values ascribed to the
      self and those ascribed to short- and long-term partners as well as best friends.
      Furthermore, greater BDI scores significantly predicted lesser ratings of mate
      value for the self, and hence indirectly predicted lesser ratings of mate value
      for all types of partners evaluated. LIMITATIONS: Although the data obtained from
      the MVI demonstrated good psychometric validity, external validity has not yet
      been established. CONCLUSIONS: The results are consistent with models predicting:
      (1) assortative mating by mate value, (2) differential exchange rates of mate
      value for different types of partners, (3) a negative relation between depressive
      symptoms and assessment of one's own mate value, and (4) a possibly consequential
      mismatch of mate values when one partner exhibits or recovers from significant
      depressive symptoms. The results are inconsistent with models predicting (5) a
      generalized negativity bias due to depression.

PMID- 12798252
TI  - Gabapentin in antipsychotic-induced tardive dyskinesia: results of 1-year follow
      up.
AB  - BACKGROUND: In a previous study, improvement of antipsychotic-induced
      blefarospasm and involuntary oral-mandibulo movements were observed with the use
      of the anticonvulsant drug gabapentin among affectively ill patients who had been
      exposed to maintenance neuroleptics. The results reported in the present paper
      represent the sequel to the previous study. METHODS: The purported efficacy of
      gabapentin in the treatment of tardive dyskinesia has been assessed in an open
      design 1-year follow-up study, in which 30 schizoaffective, bipolar I and
      schizophrenic patients from seven Italian centres were evaluated by means of
      AIMS. The results showed a statistically significant time-related decrease in
      AIMS scores. The mean percentage of improvement at AIMS was 47.5+/-18.2%. An
      improvement of more than 35% after 1 year in 76% of the subjects who completed
      the trial (n=25) and in 63.3% of the entire sample admitted to the study was
      revealed. LIMITATION: Open trial. CONCLUSION: The introduction of new
      antipsychotic drugs has probably already limited the problems related to tardive
      dyskinesia. However, this type of side-effect is also observed during the course
      of treatment with atypical neuroleptics albeit with a lesser frequency. The fact
      that gabapentin treatment may have further improved clinical conditions of
      patients in whom therapeutic protocols had already been modified, appears to
      suggest exertion of a possible synergic action by the new neuroleptics on tardive
      dyskinesia.

PMID- 12798254
TI  - Screening for bipolar disorders using the Hypomanic Personality Scale.
AB  - INTRODUCTION: The Hypomanic Personality Scale (Hyp; Eckblad and Chapman, 1986)
      might be an indicator for the risk for bipolar affective disorders. We
      investigated whether the results with American samples can be replicated in a
      different sample. METHODS: The participants (N=224) completed a questionnaire
      package including the Hyp Scale and were independently interviewed with a
      psychiatric interview schedule. RESULTS: Compared to the control group, persons
      scoring high on the Hyp scale reported significantly more manic or hypomanic
      episodes but not episodes of major depression. Correspondingly, the risk group
      exceeded the control group only on the rate of bipolar affective disorders (20.8%
      vs. 1.3%) but not unipolar depression, anxiety disorders, or other psychiatric
      conditions. CONCLUSIONS: It seems that the Hyp scale assesses a similar concept
      in American and German samples, and that it might be a useful tool to study more
      closely the processes associated with the development of bipolar spectrum
      disorders.

PMID- 12798255
TI  - Prevalence and correlates of DSM-IV major depression in an Australian national
      survey.
AB  - BACKGROUND: Community surveys have reported prevalence of depressive disorders in
      adult populations since the 1970s. Until recently, no epidemiological studies of
      the same magnitude have been conducted to provide a profile of the adult
      population in Australia. This study examines the current (30-day) prevalence and
      correlates of major depression in the adult Australian population using data from
      the National Survey of Mental Health and Well-being, and compares the results
      with other national studies. METHODS: Data were derived from a national sample of
      10,641 people 18-75+ years of age surveyed using the computerised version of the
      Composite International Diagnostic Interview Version 2.1. RESULTS: The overall
      weighted prevalence of current (30-day) major depression was 3.2% with the
      highest rate (5.2%) being found in females in mid life. This rate is between
      those of the USA National Comorbidity Survey and the Epidemiological Catchment
      Area study, and similar to the British Psychiatric Morbidity Survey. The
      strongest correlates for reported current major depression include being
      unemployed, smoking, having a medical condition, followed by being in mid life,
      previously married, and female. Living with a partner and drinking 1 to 2 glasses
      of alcohol per day were least correlated. Some correlates of major depression
      relate to social disadvantage and lifestyle issues. LIMITATIONS: The study design
      does not allow definition of direction of causality. CONCLUSION: Lowering the
      prevalence rate of major depression will require close attention to public health
      approaches to address the relationships between smoking, social isolation, poor
      health, mood and physical well-being. The best focus for this approach may be
      primary care settings.

PMID- 12798256
TI  - Heterogeneity of admission history among patients with bipolar disorder.
AB  - BACKGROUND: Patients on a first admission for bipolar disorder often have a
      history of other psychiatric diagnoses for previous admissions. AIMS: The current
      study examines the time course and diagnoses of psychiatric admissions prior and
      subsequent to a first hospitalisation for a diagnosis of bipolar disorder.
      METHOD: The prior admission histories (over the period 1965-1989) of 1167
      patients who had been hospitalised in state mental health facilities with their
      first admission with diagnosis of bipolar disorder between 1983 and 1989 were
      examined. RESULTS: A total of 542 (46.4%) patients had at least one previous
      hospitalisation with a psychiatric diagnosis other than bipolar disorder. Two
      prominent groups emerged; one group which had primarily a history of prior
      admissions with diagnoses of depression over 1-3 years, and a second which mainly
      had previous admissions for schizophrenia, over a period longer than for those
      with a primarily depressive history. The group with a history of schizophrenia
      was significantly younger and had a greater number of admissions prior to the
      first bipolar disorder diagnosis than the depression group. LIMITATIONS: This was
      a record-based study which did not examine cases which were not hospitalised.
      CONCLUSIONS: There appeared to be three distinct patterns of prior presentations
      in those patients admitted with a diagnosis of bipolar disorder.

PMID- 12798257
TI  - Platelet 5-HT concentration and comorbid depression in war veterans with and
      without posttraumatic stress disorder.
AB  - BACKGROUND: The serotonergic system is implicated in the pathophysiology of
      posttraumatic stress disorder (PTSD) and depression. The present study focused on
      platelet serotonin (5-HT) concentration and symptoms of comorbid depression in
      war veterans with or without PTSD. METHODS: PTSD and depression were evaluated
      using Clinician Administered PTSD Scale, Davidson Trauma Scale, Montgomery-Asberg
      Depression Rating Scale and Hamilton Anxiety Scale. Sixty-five male drug-free war
      veterans (48 with PTSD and 17 without PTSD) and 65 age- and sex-matched healthy
      controls were studied. RESULTS: Comorbid depression occurred in 54 and 31% of war
      veterans with PTSD and without PTSD, respectively. Platelet 5-HT concentration
      was similar in the groups of depressed and nondepressed war veterans with or
      without PTSD and healthy controls. Platelet 5-HT concentration was found to
      differ between war veterans with various degrees of appetite loss. A positive
      correlation was observed between platelet 5-HT concentration and severity of
      appetite loss in veterans with PTSD. There was no relationship between platelet 5
      HT concentration and severity of other symptoms of PTSD or depression.
      LIMITATIONS: War veterans included in the study were outpatients. CONCLUSIONS:
      War veterans with PTSD had a high incidence of comorbid depression, that was not
      related to platelet 5-HT concentration. The marked relationship between platelet
      5-HT concentration and severity of appetite loss, suggested that 5-HT system is
      involved in the regulation of appetite, at least in depressed war veterans with
      PTSD.

PMID- 12798258
TI  - Depression and suicidal behavior in adolescent inpatients with obsessive
      compulsive disorder.
AB  - BACKGROUND: To investigate the prevalence and correlations of suicidal behavior
      in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients.
      METHODS: A total of 348 adolescents, representing consecutive admissions to an
      adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had
      schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had
      an eating disorder. In addition, 87 normal community controls were assessed. All
      subjects were assessed for suicidal behavior by the Childhood Suicide Potential
      Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness
      by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and
      for aggression by the Yudowsky Overt Aggression Scale. RESULTS: All the
      psychiatrically ill subjects, including those with OCD, had high levels of
      depression, anxiety and impulsiveness, which were far higher than those of the
      controls. The rate of attempted suicide was, however, much lower in the OCD
      subjects. In addition, there was a significant inverse correlation between
      suicidal behavior levels on the CSPS and depression in the OCD subjects, while
      all other subjects showed the expected significant positive correlation between
      level of suicidal behavior and depression. LIMITATIONS: This study looked at a
      referred population and generalization to outpatient and community samples cannot
      be made. Distinguishing between the primary and the comorbid diagnosis is
      difficult and some findings are based on small sample size and therefore may be
      vulnerable to type I error. CONCLUSIONS: Although suicidal ideation and
      depressive symptoms are common in OCD adolescent inpatients, they seem to be
      protected against suicide attempts. The inverse relationship between suicidal
      behavior and depression may mean that suicidal behavior is, in some ways,
      qualitatively different from that seen in other psychiatrically ill adolescents.

PMID- 12798259
TI  - Clinical differences between bipolar II depression and unipolar major depressive
      disorder: lack of an effect of age.
AB  - BACKGROUND: Inconsistent clinical differences were reported in bipolar II versus
      unipolar depression. Age difference may be a confounding factor. Study aims were
      to describe the clinical and family history features of bipolar II versus
      unipolar depression, and to control for the possible confounding effect of age on
      clinical features. METHODS: Consecutive 126 unipolar and 187 bipolar II major
      depressive episode (MDE) outpatients were interviewed with the Structured
      Clinical Interview for DSM-IV. Variables studied were gender, age, age of onset,
      MDE recurrences, axis I comorbidity, MDE severity, psychotic, melancholic, and
      atypical features, depression chronicity, melancholic, atypical, and hypomanic
      symptoms, depressive mixed state-DMX3 (MDE+three or more concurrent hypomanic
      symptoms), and mood disorders family history. The effect of age on clinical
      differences was controlled by logistic regression (by adding age as an
      independent variable after each independent variable). RESULTS: Bipolar II had
      significantly lower age, lower age of onset, more recurrences, more atypical
      features, more DMX3, more family history of bipolar II and MDE. Almost all the
      clinical differences found significant in the first analysis resulted still
      significant when controlled for age. LIMITATIONS: Single interviewer, non-blind,
      cross-sectional assessment, bipolar II diagnosis based on history. CONCLUSIONS:
      Results confirmed previous findings, and showed that bipolar II-unipolar MDE
      clinical differences were not related to age.

PMID- 12798260
TI  - The maternity blues and Hong Kong Chinese women: an exploratory study.
AB  - BACKGROUND: The maternity blues have been studied world-wide and are generally
      regarded as a cross-cultural phenomenon. However, low prevalence rates of the
      blues have been reported recently in studies of Japanese women. The purposes of
      this study are, firstly, to establish whether the low prevalence noted in
      Japanese women is also found in another group of Asian women, that is, Hong Kong
      Chinese women, and secondly, to describe the manifestations of the blues in this
      group of women. METHOD: A prospective survey involving a convenience sample of 88
      women, recruited on the first day after normal or operative vaginal delivery.
      Participants completed a blues self-rating scale (Stein's Daily Scoring System)
      every day for the first 7 days after delivery. Data were analysed mainly in terms
      of descriptive statistics. RESULTS: 39 (44.3%) women experienced an episode of
      the blues during the first week after delivery. The manifestations of the blues
      showed a typical peaking on the 5th postnatal day. LIMITATIONS: This is a short
      term exploratory study. Further investigation is required into the factors
      influencing or precipitating the blues, particularly from the cultural
      perspectives of childbearing Hong Kong Chinese women. CONCLUSION: Hong Kong
      Chinese women experience the maternity blues in similar ways to those reported by
      studies of women in other countries and cultures, with the exception of those
      describing the blues in Japanese women.

PMID- 12798261
TI  - The mechanism of self-recognition in humans.
AB  - Recognizing oneself as the owner of a body and the agent of actions requires
      specific mechanisms which have been elucidated only recently. One of these
      mechanisms is the monitoring of signals arising from bodily movements, i.e. the
      central signals which contribute to the generation of the movements and the
      sensory signals which arise from their execution. The congruence between these
      two sets of signals is a strong index for determining the experiences of
      ownership and agency, which are the main constituents of the experience of being
      an independent self. This mechanism, however, does not account from the frequent
      cases where an intention is generated but the corresponding action is not
      executed. In this paper, it is postulated that such covert actions are internally
      simulated by activating specific cortical networks or representations of the
      intended actions. This process of action simulation is also extended to the
      observation and the recognition of actions performed or intended by other agents.
      The problem of disentangling representations that pertain to self-intended
      actions from those that pertain to actions executed or intended by others, is a
      critical one for attributing actions to their respective agents. Failure to
      recognize one's own actions and misattribution of actions may result from
      pathological conditions which alter the readability of these representations.

PMID- 12798262
TI  - How necessary is the activation of the immediate early gene zif268 in synaptic
      plasticity and learning?
AB  - The immediate early genes (IEGs) are activated rapidly and transiently in
      response to a multitude of stimuli. The zif268 belongs to a category of
      regulatory IEGs that activate downstream target genes and is considered to be a
      triggering mechanism to activate the genomic response in neurons. Several studies
      have shown that zif268 mRNA is upregulated during different forms of associative
      learning, and following tetanic stimulation that induces long-lasting LTP. To
      date, there is a general consensus that zif268 activation may constitute a
      critical mechanism for the encoding of long-lasting memories, however this is
      based on relatively few studies. Given the fact that zif268 can be activated by a
      number of different types of stimuli, it becomes important to determine exactly
      how it may be implicated in memory. Examination of the current literature
      suggests that zif268 is necessary in the processing of several types of memory,
      however, it is not entirely clear what aspects of memory zif268 may be implicated
      in. Here, we review the existing literature and emphasise that understanding the
      signalling pathways that lead to activation of the IEGs and the downstream
      targets of these genes will advance our understanding of how functional
      activation of zif268 may be implicated in processing long-term memories.

PMID- 12798263
TI  - Role of platelet activating factor in triazolobenzodiazepines-induced retrograde
      amnesia.
AB  - Benzodiazepine (diazepam), triazolobenzodiazepines (brotizolam, triazolam) and
      platelet activating factor (PAF) antagonist (BN 52021) are administered to mice
      before acquisition and retrieval trials conducted using Morris water maze.
      Benzodiazepine has produced only anterograde amnesia and it has not produced
      retrograde amnesia. Triazolobenzodiazepines have produced both anterograde and
      retrograde amnesia. PAF antagonist (BN 52021) has only produced retrograde
      amnesia and it has not produced anterograde amnesia. The anterograde amnesia
      produced by benzodiazepine and triazolobenzodiazepines, has been prevented by
      benzodiazepine receptor antagonist (flumazenil). It suggests that benzodiazepine-
      and triazolobenzodiazepines-induced anterograde amnesia may be mediated through
      benzodiazepine receptors. On the other hand, retrograde amnesia produced by PAF
      antagonist (BN 52021) and triazolobenzodiazepines has been attenuated by PAF and
      PAF acetyl hydrolase inhibitors such as cigarette smoke extract (CSE) and
      phenylmethanesulfonylflouride. It suggests that triazolobenzodiazepine-induced
      retrograde amnesia may be mediated through blockade of PAF receptors.

PMID- 12798264
TI  - Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory
      consolidation of an inhibitory avoidance learned response in C57BL/6J mice.
AB  - The still unknown contribution of the D4 receptors to memory consolidation was
      studied examining the memory effects of the dopamine D4 agonist PD168,077, the
      putative dopamine D4 antagonist L745,870, their mutual combination, and the
      combination of the D4 agonist with representative compounds acting as agonist or
      antagonist on the D1, D2 and the D3 receptors. Memory consolidation was assessed
      in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the
      compounds being injected immediately after training (foot-shock) and performance
      measured 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory
      performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and
      at doses higher than 1mg/kg impaired memory performance. PD168,077 did not affect
      the paradoxical promnesic effect of low doses (0.1-0.5mg/kg) of L745,870, but
      antagonised the memory-impairing effect induced by 5mg/kg L745,870. The D1
      antagonist SCH23390 (0.025-0.05 mg/kg) and the D2 antagonist eticlopride (0.01
      0.05 mg/kg) antagonised the promnesic effects of PD168,077, which attenuated the
      decreasing effect on memory consolidation of both D1 and D2 antagonists.
      Accordingly, the D1 agonist SKF38393 (5-20mg/kg) and the D2 agonist quinelorane
      (0.1-1 mg/kg) both synergistically magnified the memory-improving effects of the
      D4 agonist. The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the
      promnesic effects induced by the D4 agonist, which nevertheless abolished the
      U99194A-induced promnesic effects. Additionally, the amnesic effects produced by
      the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These
      results suggest a potential role of dopamine D4 receptors in memory
      consolidation, which would be similar to that of the D1 and D2 receptors and
      probably opposite to that of the D3 receptors.

PMID- 12798265
TI  - Open-field behavior withstands drastic changes in arena size.
AB  - Individual voles were tested on successive days under increasing, decreasing, or
      randomly changing arena size. Locomotor behavior was adjusted to arena size by
      (i) preserving the same level of activity, (ii) taking longer but less frequent
      trips in smaller arenas in contrast to taking more frequent yet shorter trips in
      the larger arenas, and (iii) moving in the entire space available for exploration
      in the smaller arenas in contrast to remaining along the walls of the open field
      in the larger arenas. The effect of testing order was minimal, probably being
      related to increased novelty under increasing arena size, as opposed to
      habituation under decreasing arena size, when parts of the same area were re
      explored. These behavioral changes averaged up to a two-fold difference compared
      with the larger six-fold change in the perimeter and 44-fold change in the area
      of the open field. The modest change in open-field behavior indicates that it has
      a solid spatio-temporal structure that withstands extensive environmental
      changes. This behavioral stability and consistency further validates studies of
      pharmacological, neurological, and genetic preparations that use behavior in a
      small open field as representation of the general pattern of behavior.

PMID- 12798266
TI  - Immunohistochemical fluorescence intensity reduction of brain somatostatin in the
      impairment of learning and memory-related behaviour induced by olfactory
      bulbectomy.
AB  - The role of brain somatostatin (SST) on memory function after olfactory
      bulbectomy (OBX) was investigated by using the passive-avoidance task and
      immunohistochemical analyses in mice. The present study indicated that the
      learning and memory-related behaviour was impaired on the 7th and 14th day, but
      not on the 1st day after OBX. The impairment of learning and memory-related
      behaviour on the 14th day after OBX was dose-dependently reversed by
      intracerebroventricularly administered SST (1 microg per mouse). To ascertain the
      correlation between SST in mouse brain and the impairment of learning and memory
      related behaviour induced by OBX, the immunohistochemical distribution of brain
      SST was determined by fluorescence intensity using two-dimensional
      microphotometry. The intensity of SST fluorescence was low in the hippocampus on
      the 14th day after OBX in comparison with Sham controls. These results suggest
      that SST in the hippocampus is related to the impairment of learning and memory
      related behaviour induced by OBX.

PMID- 12798267
TI  - Reduced attention in mice overproducing corticotropin-releasing hormone.
AB  - Data from several studies suggest that unrestrained secretion of corticotropin
      releasing hormone in the CNS produces several signs and symptoms of depression.
      Recent evidence indicates that blockade of the CRH receptor 1 reduced depression
      scores in depressed patients. One of the symptoms that occur is depression is
      impairment in attentional processes. Whether these impairments are due to
      alterations in the CRH system are so far unknown. In order to investigate whether
      overproduction of CRH alters attentional process, transgenic mice overproducing
      CRH were tested on an operant five choice serial reaction time task, a task which
      taxes sustained and divided attention. Mutants showed impaired autoshaping.
      During initial discrimination learning, transgenics performed below wildtype
      level, but with extended training with long stimulus durations, transgenic
      animals reached similar accuracy levels as wildtype mice. When animals were
      tested at shortest stimulus duration (0.5s), a mild but significant impairment in
      accurate responding emerged in transgenics. This was accompanied by longer
      correct response latencies, while incorrect latencies did not differ between
      groups, suggesting attentional impairment in CRH transgenics. Because these
      animals have been reported to also show increased anxiety-related behaviour,
      animals were treated with the anxiolytic benzodiazepine diazepam. Diazepam failed
      to affect accuracy, but transgenic mice showed a stronger behavioural
      disinhibition. This suggests that the attentional impairment seen in CRH
      overexpressors is independent of alterations in anxiety-like behaviour. These
      findings may have implications for understanding the pathophysiology of
      psychiatric disorders such as depression, where it has been suggested that an
      overactivity of the CRH system accounts for a variety of symptoms, including
      hyper-arousal and attentional impairment.

PMID- 12798268
TI  - Effect of mental imagery of a motor task on the Hoffmann reflex.
AB  - Research has found that mental imagery of a motor task may influence the Hoffmann
      reflex (H-reflex). However, this work has not examined the potential influence of
      background EMG (BEMG) on the H-reflex. In this study 23 adult participants
      (M=23.3 years, S.D.=3.2) were instructed to mentally image plantar flexion of the
      right foot at four intensities: 40, 60, 80 and 100% of maximum voluntary
      contraction (MVC) after completing practice trials of actual contractions at
      these intensities. Dependent measures were the BEMG activity and the peak-to-peak
      amplitude of the H-reflex. On each trial the peak-to-peak amplitude of the soleus
      H-reflex was measured in the right leg and averaged, BEMG (40 ms bin) was
      measured in the soleus and tibialis anterior of both legs. Following trials of
      plantar flexion at the target intensities participants completed 5 imagery trials
      at each intensity and 15 trials while performing this motor task. Five resting
      control trials were administered prior to and following the completion of all
      test trials. Administration of test trials was randomized within conditions. A
      main effect (P<0.05) for trial blocks was observed for H-reflex amplitude but not
      BEMG. The H-reflex increased linearly throughout testing, suggesting that the H
      reflex was modified by the practice of imagery rather than the intensity of the
      imagined task.

PMID- 12798269
TI  - Acute and conditioned sickness reduces morphine analgesia.
AB  - Animals made ill by intraperitoneal injection with toxins, such as lithium
      chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated
      with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive
      neurocircuitry and spinal pharmacology that underlie these effects bear the same
      features as those that mediate analgesic tolerance to morphine [Neurosci.
      Biobehav. Rev. 23 (1999) 1059]. Thus, we examined whether LiCl, LPS or cues
      paired with LiCl could reduce morphine analgesia. Morphine analgesia in the tail
      flick test was reduced 24 h but not 7 days following injection with LiCl, and 24
      h following injection with LPS. In addition, morphine analgesia was reduced in
      the hot plate test 40 min and 24 h following LiCl. Furthermore, these effects
      occurred in the absence of detectable hyperalgesia indicating that illness
      induced tolerance was not the result of an increase in pain sensitivity
      offsetting analgesia. Finally, rats tested in a context associated with LiCl
      demonstrated less morphine analgesia than rats tested in a context not associated
      with LiCl or rats naive to LiCl suggesting that illness activates descending
      mechanisms that antagonize analgesia rather than simply desensitizing opioid
      receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents
      also activate endogenous antianalgesic mechanisms.

PMID- 12798270
TI  - Mnemonic functions of dorsal striatum and hippocampus in aversive conditioning.
AB  - These experiments examined the mnemonic functions of hippocampus and dorsal
      striatum in Pavlovian aversive conditioning. Rats were trained in a single
      session by presenting three paired tones and footshocks. Immediately after
      training, they were given microinjections of D-amphetamine or vehicle into either
      dorsal hippocampus or dorsal striatum. Twenty-four hours later conditioned
      freezing (measured as cessation of movement by infrared motion detectors) to the
      experimental context and to the tone were measured separately. Compared to
      vehicle injections, amphetamine injections into dorsal hippocampus significantly
      increased conditioned freezing to the context but not to the tone. Injections
      into dorsal striatum increased conditioned freezing to both the context and the
      tone. These results converge with findings from lesion experiments suggesting
      that hippocampus is involved in aversive conditioning with contextual CSs only,
      and that dorsal striatum is involved in aversive conditioning with both
      contextual and discrete cue CSs. The functions of the these two structures in
      relation to that of the amygdala in the mediation of conditioned freezing are
      discussed.

PMID- 12798271
TI  - Visual lateralization in the bottlenose dolphin (Tursiops truncatus): evidence
      for a population asymmetry?
AB  - A previous behavioural study with a single bottlenose dolphin had reported a
      right eye superiority in visual discrimination tasks, indicating a left
      hemisphere dominance for visual object processing. The presence of a functional
      asymmetry demonstrated with one individual shows that this function can be
      lateralized in this single animal, but cannot reveal if this represents a
      population asymmetry. Therefore, we conducted a series of visual discrimination
      experiments with three individuals of Tursiops truncatus under monocular
      conditions. The tested animals had to distinguish between simultaneously
      presented stimulus pairs of different patterns, whereby one stimulus was always
      defined to be correct. Additionally, the animals were observed for their free eye
      use during training and introduction of new items. The present data set revealed
      a right eye advantage (left hemisphere dominance) for all tested animals and a
      predominance of right eye use during daily activities. These results make it
      possible that bottlenose dolphins are lateralized for visual pattern
      discrimination at the level of a population asymmetry. Against the background of
      similar data in other vertebrates, a left hemisphere dominance for pattern
      discrimination points to the possibility that dolphins exploit local visual
      details instead of global configurational features to recognize and memorize
      visual stimuli.

PMID- 12798272
TI  - Posttraining lesion of the superior colliculus interferes with feature-negative
      discrimination of fear-potentiated startle.
AB  - Though much is known about the neural circuits involved in the elicitation of
      fear, little is known about the neural circuits responsible for the reduction of
      fear. The present experiments investigated the contribution of the superior
      colliculus (SC) and the dorsal periacquaductal gray (dPAG) in the reduction of
      conditioned fear produced by an auditory feature trained in a feature-negative
      discrimination procedure. In this procedure, light plus foot shock training
      trials are interspersed with trials in which the light is preceded by a noise and
      this noise and light compound is not followed by foot shock. At the end of this
      feature-negative discrimination training, rats were given excitotoxic lesions of
      the SC or dPAG. Feature-negative discrimination of fear was assessed with the
      fear-potentiated startle effect in which conditioned fear is operationally
      defined as potentiated startle amplitude in the presence versus the absence of
      the light. Feature-negative discrimination of fear is evidenced by a reduction in
      fear-potentiated startle to the light when the noise feature accompanies the
      light. Lesions of the SC, but not the dPAG, interfered with feature-negative
      discrimination of fear-potentiated startle suggesting that the SC plays a role in
      feature-negative discrimination of fear. Both SC and dPAG lesions facilitated
      startle amplitude in the absence of the light suggesting that these structures
      may exert a tonic inhibition on the acoustic startle reflex. The SC receives
      polymodal sensory information and is known to project forebrain areas involved in
      the production of conditioned fear. Thus, the SC may be an important component of
      the feature-negative discrimination circuit.

PMID- 12798273
TI  - The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic
      related defensive responses in rats.
AB  - It has been proposed that the ascending dorsal raphe (DR)-serotonergic (5-HT)
      pathway facilitates conditioned avoidance responses to potential or distal
      threat, while the DR-periventricular 5-HT pathway inhibits unconditioned flight
      reactions to proximal danger. Dysfunction on these pathways would be,
      respectively, related to generalized anxiety (GAD) and panic disorder (PD). To
      investigate this hypothesis, we microinjected into the rat DR the benzodiazepine
      inverse receptor agonist FG 7142, the 5-HT(1A) receptor agonist 8-OH-DPAT or the
      GABA(A) receptor agonist muscimol. Animals were evaluated in the elevated T-maze
      (ETM) and light/dark transition test. These models generate defensive responses
      that have been related to GAD and PD. Experiments were also conducted in the ETM
      14 days after the selective lesion of DR serotonergic neurons by 5,7
      dihydroxytriptamine (DHT). In all cases, rats were pre-exposed to one of the open
      arms of the ETM 1 day before testing. The results showed that FG 7142 facilitated
      inhibitory avoidance, an anxiogenic effect, while impairing one-way escape, an
      anxiolytic effect. 8-OH-DPAT, muscimol, and 5,7-DHT-induced lesions acted in the
      opposite direction, impairing inhibitory avoidance while facilitating one-way
      escape from the open arm. In the light/dark transition, 8-OH-DPAT and muscimol
      increased the time spent in the lighted compartment, an anxiolytic effect. The
      data supports the view that distinct DR-5-HT pathways regulate neural mechanisms
      underlying GAD and PD.

PMID- 12798274
TI  - Protective effect of 5-HT1B receptor gene deletion on the age-related decline in
      spatial learning abilities in mice.
AB  - We previously observed that 5 months old serotonin 1B receptor knockout (5
      HT1BKO) mice exhibited a facilitation of learning in a long-term spatial memory
      task in a water maze. In this study, we attempted to assess whether this effect
      might persist during aging. We compared the performances of young-adult (3 months
      old) and aged (22 months old) 5-HT1BKO and wild type (WT) mice in the same task.
      Young-adult and aged KO mice exhibited facilitated acquisition of the reference
      memory task as compared to their respective WT controls. Generally, the
      performance of aged KO was similar to that of young-adult WT on the parameters
      defining performance and motor (swim speed) aspects of the task. During probe
      trials, all mice presented a spatial selectivity, which was, however, less
      pronounced in aged than in young-adult WT. No such age-related effect was
      observed in KO mice. In a massed spatial learning task, aged KO and WT mice
      globally exhibited the same level of performance. Nevertheless, young-adult and
      aged KO mice were superior to their WT controls as concerns the working memory
      component of the task. The data suggest that 5-HT1BKO mice are more resistant
      than WT to age-related memory decline as concerns both reference/long-term and
      working/short-term spatial memory.

PMID- 12798275
TI  - Combined restraint and cold stress in rats: effects on memory processing in
      passive avoidance task and on plasma levels of ACTH and corticosterone.
AB  - The effect of restraint stress combined with water immersion (IMO+C), applied at
      various intervals before and after the acquisition of a passive avoidance task,
      was studied in rats. The procedure started with two pre-training trials. On the
      single training trial the rats received a footshock (0.3 mA, 3s) after they
      entered the preferred dark compartment. The exposure to IMO+C lasting 1 h
      terminated 4 or 1 h before application of the footshock or started immediately or
      3 h after this aversive stimulus. Retention tests were performed 1 and 2 days
      after the acquisition trial. In an attempt to relate the behavioural responses to
      the stressor with plasma levels of two stress hormones we measured ACTH and
      corticosterone under similar conditions as were used in the behavioural
      experiments. IMO+C exposure terminating 1 h before the training resulted in very
      short avoidance latencies during retention testing. A similar impairment of
      retention test performance was found in animals exposed to the stressor
      immediately after training. When IMO+C exposure terminated 4 h before training
      the stressed rats exhibited comparably long avoidance latencies as shown by the
      controls. IMO+C presented 3 h after acquisition trial also did not influence
      retention of avoidance learning. The hormones were estimated 1 and 4 h after
      IMO+C, both in the absence and presence of footshock. Both ACTH and
      corticosterone were significantly increased 1 h after IMO+C termination, and
      their plasma levels returned to control values within 4 h. Footshock alone
      increased plasma corticosterone, however, the hormone levels were significantly
      lower than those estimated after IMO+C terminating 1 h before blood collection.
      Footshock substantially increased ACTH levels in rats exposed to IMO+C 1 h before
      footshock, but not in stressed rats with already high levels of corticosterone.
      In conclusion, IMO+C represents a strong stress stimulus exerting amnesic effect
      when applied shortly before or after the acquisition trial. Further, the findings
      indicate the restraint and cold stressor to interfere with consolidation of
      passive avoidance response. We suggest that the moderate circulating levels of
      corticosterone found after footshock may be positively related to the memory
      consolidation, while the exceedingly high levels have an opposite effect.

PMID- 12798276
TI  - Standard housed rats are more sensitive to rewards than enriched housed rats as
      reflected by their anticipatory behaviour.
AB  - The present study was designed to investigate the effects of potentially
      stressful standard housing conditions for laboratory rats on the sensitivity to
      rewards as reflected by their anticipatory behaviour for sucrose. This
      anticipatory response is evoked in a conditioning paradigm in which a sucrose
      reward is repeatedly announced by a stimulus. The underlying neurocircuitry of
      this anticipatory response in expectation of a reward involves mesolimbic
      dopaminergic systems of which it is known that they can be sensitised by
      stressors. The results show that the anticipatory response for the sucrose reward
      is stronger in the standard housed animals which indicates that these animals are
      more sensitive to the reward than the enriched animals. From this, it is
      concluded that standard housed rats are stressed which is likely to be caused by
      deprivation of the ability to satisfy behavioural needs in these impoverished
      housing conditions.

PMID- 12798277
TI  - Repetitive acute pain in infancy increases anxiety but does not alter spatial
      learning ability in juvenile mice.
AB  - We assessed the long-term behavioural effects of a single acute or repetitive
      inflammatory pain experienced during infancy. Groups of male and female CD1 mice
      were subjected to either an acute single pain, i.e. a tail clip or sham pain at
      P8, or acute repetitive pain in the form of needle pricks or sham pain from P8 to
      P14. All of the subjects were tested in the elevated plus maze at P30 and in the
      Morris Water Maze from P31 to P38. Mice in the acute single pain and sham groups
      did not differ on measures of anxiety in the plus maze. Mice in the repetitive
      pain group demonstrated significantly more anxious behaviours than controls in
      the elevated plus maze as they spent less time in the open arms, made fewer open
      arm entries, displayed fewer head dips and showed more stretch attend postures.
      There were no effects of single or repetitive pain treatments in the latency to
      find the hidden platform in the Morris Water Maze. Overall, these data suggest
      that acute repetitive pain experienced during infancy may increase anxiety later
      in life but it does not influence spatial learning as measured in the Morris
      Water Maze. The origin of the anxiogenic profile shown in the acute repetitive
      pain mice may be a result of changes in neural circuitry or context dependent
      learning and is currently under further investigation with this paradigm.

PMID- 12798278
TI  - Acute alcohol administration improves skilled reaching success in intact but not
      6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and
      anxiolytic effects of alcohol.
AB  - Low doses of alcohol impair movement and reduce anxiety. Most assessments of
      movement under ethyl alcohol (alcohol) in the rat have been tests of whole body
      movements, however. There has been no examination of the effects of alcohol on
      skilled limb movements, such as reaching for food with a forelimb. This was the
      purpose of the present study. Rats were trained to reach through a slot of a box
      with a forelimb in order to obtain a food pellet located on an external shelf.
      Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12
      or 20% (v/v) solution) in separate tests to establish a relationship between
      alcohol ingestion and skilled reaching performance. Acute treatment with all
      doses of alcohol impaired postural support, but doses of 8 and 12% alcohol
      improved skilled reaching success. Qualitative analysis of the movements used for
      reaching at doses of 8 and 12% indicated that some limb components of the
      reaching movement were also impaired, perhaps secondarily due to impaired
      posture. In contrast, the reaching success of rats with unilateral dopamine
      depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the
      nigrostriatal bundle, was impaired by the same dose of alcohol that improved
      reaching success in control rats. The finding of improved success in reaching
      associated with reduced postural support in normal rats suggests a differential
      action of alcohol on movement subsystems underlying posture relative to skilled
      movement that depends upon an intact dopaminergic system. The results are also
      discussed with respect to the relationship of subsystems of movement and anxiety.

PMID- 12798279
TI  - m-CPP-induced self-grooming is mediated by 5-HT2C receptors.
AB  - m-Chlorophenylpiperazine (m-CPP), a potent 5-HT receptor agonist, is known to
      induce self-grooming in rats and exacerbate symptoms in patients with obsessive
      compulsive disorder (OCD). To characterise the possible role, 5-HT(2B) and 5
      HT(2C) receptors play in m-CPP-induced self-grooming, subtype-selective receptor
      antagonists were used. m-CPP significantly increased the amount of self-grooming
      in male Sprague-Dawley rats. This effect followed a bell-shaped dose-response
      curve with a peak at 0.6 mg/kg, i.p. Pretreatment with SB-242084, a subtype
      selective 5-HT(2C) receptor antagonist (0.1-0.5 mg/kg, i.p.), reversed m-CPP
      induced self-grooming. In contrast, pretreatment with the subtype-selective 5
      HT(2B) receptor antagonist SB-215505 (1 mg/kg, i.p) did not block the effect of m
      CPP. Two days after depletion of brain 5-HT by p-chlorophenylalanine (p-CPA, 2 x
      50, 2 x 100 mg/kg, i.p.) m-CPP-induced responses were significantly enhanced
      compared to controls. Our studies provide evidence that direct activation of 5
      HT(2C) receptors mediate m-CPP-induced self-grooming and the depletion of brain 5
      HT sensitizes these receptors.

PMID- 12798280
TI  - Reward modulates neuronal activity in the hippocampus of the rat.
AB  - In the hippocampus of freely moving rats, neurons have been recorded that fire
      predominantly when the animal travels through a particular area while exploring
      the environment (so-called 'place cells'). This study investigates if the
      neuronal firing characteristics of such cells are modulated by attention,
      expectation of reward or memory load. A total of 16 electrodes were implanted in
      the CA1 region of the hippocampus of 3-month-old Long-Evans rats. Using a tetrode
      recording system, single neurons were recorded while a rat explored an 8-arm maze
      and retrieved pellets at the end of each arm. It was found that 31 out of 67
      neurons showed place cell characteristics, while the other cells either fired in
      more than one place or fired along whole arms of the maze. Interestingly, 11 of
      the 31 neurons showed enhanced firing activity when the animal entered a baited
      arm but did not fire when the arm was visited again after the bait had been
      retrieved. In a second experiment, only four out of eight arms were baited.
      Firing rates of 46 neurons were analysed, and all cells (spatial or non-spatial)
      fired more in baited arms than in non-baited ones (P<0.001). In a reversal task
      in which the previously unbaited four arms were subsequently baited, neuronal
      activity was increased in the newly baited arms (42 cells analysed, P<0.001).
      Since no alterations to the maze or cues have been made, we interpret the
      increased firing probability of neurons in baited arms compared to unbaited arms
      as a correlate for 'attention' or 'expectation'.

PMID- 12798281
TI  - Darting behavior: a quantitative movement pattern designed for discrimination and
      replicability in mouse locomotor behavior.
AB  - In the open-field behavior of rodents, Software for Exploring Exploration (SEE)
      can be used for an explicit design of behavioral endpoints with high genotype
      discrimination and replicability across laboratories. This ability is
      demonstrated here in the development of a measure for darting behavior. The
      behavior of two common mouse inbred strains, C57BL/6J (B6) and DBA/2J (D2), was
      analyzed across three different laboratories, and under the effect of cocaine or
      amphetamine. "Darting" was defined as having higher acceleration during
      progression segments while moving less during stops. D2 mice darted significantly
      more than B6 mice in each laboratory, despite being significantly less active.
      These differences were maintained following cocaine administration (up to
      20mg/kg) and only slightly altered by amphetamine (up to 5mg/kg) despite a
      several fold increase in activity. The replicability of darting behavior was
      confirmed in additional experiments distinct from those used for its design. The
      strategy leading to the darting measure may be used to develop additional
      discriminative and replicable endpoints of open-field behavior.

PMID- 12798282
TI  - Effects of ovariectomy and calcium deficiency on learning and memory of eight-arm
      radial maze in middle-aged female rats.
AB  - There is increasing evidence that estrogen and calcium ion are involved in
      learning and memory. In the present study, to examine the effect of estrogen
      deficiency and low-calcium diet on learning and memory, middle-aged female Wistar
      rats (50 weeks old) were fed either a low-calcium (0.02% Ca) or a normal-calcium
      (1.25% Ca) diet throughout the experiment. Rats were ovariectomized (OVX) or sham
      operated (Sham). These animals were divided into four groups: 1) Sham group with
      normal-calcium diet [Sham-normal Ca group], 2) OVX group with normal-calcium diet
      [OVX-low Ca group], 3) Sham group with low-calcium diet [Sham-low Ca group], 4)
      OVX group with low-calcium diet [OVX-low Ca group]. Seventy-seven days after the
      OVX or Sham operation, the learning and memory abilities in the female rats were
      examined by using a radial maze task according to the method of Olton and
      Samuelson (regular trials) and using a delay-interposed task following regular
      trials. During regular trials and delay-interposed tasks, the OVX-low Ca group
      was inferior to all the other groups in accuracy of choice behavior. Both Sham
      normal Ca and Sham-low Ca groups showed more accurate choices than the OVX-low Ca
      group, but were less accurate than the Sham-normal Ca group. In addition, there
      was no significant difference in locomotor activity between any of the groups.
      These results suggest that OVX or low-calcium diet may impair learning and
      memory, and that the combination of these factors impaired more markedly when the
      rats were tested in the eight-arm radial maze. These results may also imply the
      possibility that a woman in menopause or post-menopause suffers impairment of
      learning and/or memory when intakes low-calcium diet.

PMID- 12798283
TI  - Glucose effects on a continuous performance test of attention in adults.
AB  - Increases in plasma blood glucose levels modulate memory, mood, and, to some
      extent, attention in adults. Participants in the present study were administered
      glucose (10, 100, and 500 mg/kg, or 50 g) or placebo (23.7 mg saccharin) shortly
      prior to completing the test of variables of attention (TOVA), a continuous
      performance test (CPT) commonly used to assess attention for diagnostic purposes.
      There were significant increases in blood glucose levels for the 500 mg/kg and 50
      g groups, but only the 100 mg/kg group showed significant changes in behavior in
      comparison to the saccharin group. Specifically, the 100 mg/kg group performed
      worse on measures of commission errors, post-commission responses, and post
      commission response time variability. There were no differences among the groups
      on other major variables of attention, including omission errors, response time,
      and response time variability. The results of this study demonstrate that large
      doses of glucose which increase blood glucose levels do not influence attention,
      but that a moderate dose (100 mg/kg) selectively impairs measures of impulsivity
      or disinhibition. Practitioners and researchers should maintain an awareness of
      dietary effects on attention and continue to examine micronutrients as potential
      confounds on diagnostic tests of cognition and behavior.

PMID- 12798284
TI  - Effects of valproic acid on an animal model of tardive dyskinesia.
AB  - GABAergic hypofunction in the basal ganglia is stated as an important mechanism
      underlying the pathophysiology of tardive dyskinesia. The present study
      investigates the effects of the GABA-mimetic drug valproic acid (VA) on the
      manifestation of reserpine-induced orofacial movements, an animal model of
      tardive dyskinesia. Male Wistar rats received two injections of control solution
      or of 1 mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were
      acutely treated with 50, 100, or 200 mg/kg VA or control solution and were
      observed for quantification of orofacial movements and of open-field general
      activity. The highest dose of VA inhibited the manifestation of reserpine-induced
      orofacial movements but none of the VA doses modified reserpine-induced decrease
      in open-field general activity. These results support the potential of VA as an
      effective pharmacological tool in the treatment of tardive dyskinesia.

PMID- 12798285
TI  - Mechanisms of implantation in the mouse: differentiation and functional
      importance of trophoblast giant cell behavior.

PMID- 12798286
TI  - Fibroblast growth factor (FGF)-4 can induce proliferation of cardiac cushion
      mesenchymal cells during early valve leaflet formation.
AB  - While much has been learned about how endothelial cells transform to mesenchyme
      during cardiac cushion formation, there remain fundamental questions about the
      developmental fate of cushions. In the present work, we focus on the growth and
      development of cushion mesenchyme. We hypothesize that proliferative expansion
      and distal elongation of cushion mesenchyme mediated by growth factors are the
      basis of early valve leaflet formation. As a first step to test this hypothesis,
      we have localized fibroblast growth factor (FGF)-4 protein in cushion mesenchymal
      cells at the onset of prevalve leaflet formation in chick embryos (Hamburger and
      Hamilton stage 20-25). Ligand distribution was correlated with FGF receptor
      (FGFR) expression. In situ hybridization data indicated that FGFR3 mRNA was
      confined to the endocardial rim of the atrioventricular (AV) cushion pads,
      whereas FGFR2 was expressed exclusively in cushion mesenchymal cells. FGFR1
      expression was detected in both endocardium and cushion mesenchyme as well as in
      myocardium. To determine whether the FGF pathways play regulatory roles in
      cushion mesenchymal cell proliferation and elongation into prevalvular structure,
      FGF-4 protein was added to the cushion mesenchymal cells explanted from stage 24
      25 chick embryos. A significant increase in proliferative ability was strongly
      suggested in FGF-4-treated mesenchymal cells as judged by the incorporation of 5'
      bromodeoxyuridine (BrdU). To determine whether cushion cells responded similarly
      in vivo, a replication-defective retrovirus encoding FGF-4 with the reporter,
      bacterial beta-galactosidase was microinjected into stage 18 chick cardiac
      cushion mesenchyme along the inner curvature where AV and outflow cushions
      converge. As compared with vector controls, overexpression of FGF-4 clearly
      induced expansion of cushion mesenchyme toward the lumen. To further test the
      proliferative effect of FGF-4 in cardiac cushion expansion in vivo (ovo), FGF-4
      protein was microinjected into stage 18 chick inner curvature. An assay for BrdU
      incorporation indicated a significant increase in proliferative ability in FGF-4
      microinjected cardiac cushion mesenchyme as compared with BSA-microinjected
      controls. Together, these results suggest a role of FGF-4 for cardiac valve
      leaflet formation through proliferative expansion of cushion mesenchyme.

PMID- 12798287
TI  - Cell proliferation is necessary for the determination of male fate in the gonad.
AB  - Cell proliferation has been shown to have multiple functions in development and
      pattern formation, including roles in growth, morphogenesis, and gene expression.
      Previously, we determined that the earliest known morphological event downstream
      of the male sex determining gene, Sry, is the induction of proliferation. In this
      study, we used proliferation inhibitors to block cell division during early gonad
      development, at stages before the XY gonad has committed to the testis pathway.
      Using the expression of sex-specific genes and the formation of testis morphology
      as markers of testis determination, we found that proliferation within a specific
      8-h window was critical for the establishment of the male pathway and the
      formation of the testis. Inhibition of proliferation before or after this
      critical period led to smaller gonads, but did not block testis formation. The
      critical period of proliferation coincides with the initiation of Sry expression
      and is essential for the differentiation of Sertoli cells, suggesting that
      proliferation is a vital component of the initiation of the male pathway by Sry.
      We believe these studies suggest that proliferation is involved not only in the
      elaboration of organ pattern, but also in the choice between patterns (male and
      female) in the bipotential gonad.

PMID- 12798288
TI  - Development of a rod photoreceptor mosaic revealed in transgenic zebrafish.
AB  - The number and distribution of neurons within the vertebrate retina are tightly
      regulated. This is particularly apparent in the highly ordered, crystalline-like
      arrangement of the cone photoreceptors in the teleost. In this report, using a
      transgenic line of zebrafish, a novel and developmentally regulated mosaic
      pattern of the rod photoreceptors is described. The spatial and temporal
      expression of EGFP, under the control of the Xenopus rhodopsin gene promoter, was
      nearly identical to the endogenous rhodopsin. EGFP was first detected in the
      ventral nasal retinal in an area of precocious neurogenesis referred to as the
      "ventral patch". Subsequent expression of EGFP was observed in isolated cells
      sporadically distributed across the dorsal and central retina. However, confocal
      microscopy and spatial analysis of larval eyes or retinal explants from adults
      revealed a precise arrangement to the rod photoreceptors. The rod terminals were
      arranged in regularly spaced rows with clearly identifiable telodendria linking
      neighboring cells. The rod inner segments projected through the cone mosaic in a
      predictable pattern. In the adult, the rod mosaic originated near the retinal
      margin where clusters of rods differentiated around the immature short single
      cone. In the embryo, the sporadic differentiation of the rods led to the gradual
      formation of the mosaic pattern. With the growing interest in neuronal stem
      cells, revisiting this model of neurogenesis provides an avenue to uncover
      mechanisms underlying the precise integration of new neuronal elements into a
      preexisting neural network.

PMID- 12798289
TI  - Positional cloning of a temperature-sensitive mutant emmental reveals a role for
      sly1 during cell proliferation in zebrafish fin regeneration.
AB  - Here, we used classical genetics in zebrafish to identify temperature-sensitive
      mutants in caudal fin regeneration. Gross morphological, histological, and
      molecular analyses revealed that one of these strains, emmental (emm), failed to
      form a functional regeneration blastema. Inhibition of emm function by heat
      treatment during regenerative outgrowth rapidly blocked regeneration. This block
      was associated with reduced proliferation in the proximal blastema and expansion
      of the nonproliferative distal blastemal zone. Positional cloning revealed that
      the emm phenotype is caused by a mutation in the orthologue of yeast sly1, a gene
      product involved in protein trafficking. sly1 is upregulated in the newly formed
      blastema as well as during regenerative outgrowth. Thus, sly1 is essential for
      blastemal organization and proliferation during two stages of fin regeneration.

PMID- 12798290
TI  - Myf5 and MyoD activation define independent myogenic compartments during
      embryonic development.
AB  - Gene targeting has indicated that Myf5 and MyoD are required for myogenic
      determination because skeletal myoblasts and myofibers are missing in mouse
      embryos lacking both Myf5 and MyoD. To investigate the fate of Myf5:MyoD
      deficient myogenic precursor cells during embryogenesis, we examined the sites of
      epaxial, hypaxial, and cephalic myogenesis at different developmental stages. In
      newborn mice, excessive amounts of adipose tissue were found in the place of
      muscles whose progenitor cells have undergone long-range migrations as
      mesenchymal cells. Analysis of the expression pattern of Myogenin-lacZ transgene
      and muscle proteins revealed that myogenic precursor cells were not able to
      acquire a myogenic fate in the trunk (myotome) nor at sites of MyoD induction in
      the limb buds. Importantly, the Myf5-dependent precursors, as defined by
      Myf5(nlacZ)-expression, deficient for both Myf5 and MyoD, were observed early in
      development to assume nonmuscle fates (e.g., cartilage) and, later in
      development, to extensively proliferate without cell death. Their fate appeared
      to significantly differ from the fate of MyoD-dependent precursors, as defined by
      258/-2.5lacZ-expression (-20 kb enhancer of MyoD), of which a significant
      proportion failed to proliferate and underwent apoptosis. Taken together, these
      data strongly suggest that Myf5 and MyoD regulatory elements respond
      differentially in different compartments.

PMID- 12798291
TI  - Nitric oxide acts in a positive feedback loop with BDNF to regulate neural
      progenitor cell proliferation and differentiation in the mammalian brain.
AB  - Nitric oxide (NO) is believed to act as an intercellular signal that regulates
      synaptic plasticity in mature neurons. We now report that NO also regulates the
      proliferation and differentiation of mouse brain neural progenitor cells (NPCs).
      Treatment of dissociated mouse cortical neuroepithelial cluster cell cultures
      with the NO synthase inhibitor L-NAME or the NO scavenger hemoglobin increased
      cell proliferation and decreased differentiation of the NPCs into neurons,
      whereas the NO donor sodium nitroprusside inhibited NPC proliferation and
      increased neuronal differentiation. Brain-derived neurotrophic factor (BDNF)
      reduced NPC proliferation and increased the expression of neuronal NO synthase
      (nNOS) in differentiating neurons. The stimulatory effect of BDNF on neuronal
      differentation of NPC was blocked by L-NAME and hemoglobin, suggesting that NO
      produced by the latter cells inhibited proliferation and induced neuronal
      differentiation of neighboring NPCs. A similar role for NO in regulating the
      switch of neural stem cells from proliferation to differentiation in the adult
      brain is suggested by data showing that NO synthase inhibition enhances NPC
      proliferation and inhibits neuronal differentiation in the subventricular zone of
      adult mice. These findings identify NO as a paracrine messenger stimulated by
      neurotrophin signaling in newly generated neurons to control the proliferation
      and differentiation of NPC, a novel mechanism for the regulation of developmental
      and adult neurogenesis.

PMID- 12798292
TI  - Continuous loss of oocytes throughout meiotic prophase in the normal mouse ovary.
AB  - The number of germ cells reaches the maximum just prior to entry into meiosis,
      yet decreases dramatically by a few days after birth in the female mouse, rat,
      and human. Previous studies have reported a major loss at the pachytene stage of
      meiotic prophase during fetal development, leading to the hypothesis that
      chromosomal pairing abnormalities may be a signal for oocyte death. However, the
      identification as well as the quantification of germ cells in these studies have
      been questioned. A recent study using Mouse Vasa Homologue (MVH) as a germ cell
      marker reached a contradictory conclusion claiming that oocyte loss occurs in the
      mouse only after birth. In the present study, we established a new method to
      quantify murine germ cells by using Germ Cell Nuclear Antigen-1 (GCNA-1) as a
      germ cell marker. Comparison of GCNA-1 and MVH immunolabeling revealed that the
      two markers identify the same population of germ cells. However, nuclear labeling
      of GCNA-1 was better suited for counting germ cells in histological sections as
      well as for double labeling with the antibody against synaptonemal complex (SC)
      proteins in chromosome spreading preparations. The latter experiment demonstrated
      that the majority of GCNA-1-labeled cells entered and progressed through meiotic
      prophase during fetal development. The number of GCNA-1-positive cells in the
      ovary was estimated by counting the labeled cells retained in chromosome
      spreading preparations and also in histological sections by using the ratio
      estimation method. Both methods demonstrated a continuous decline in the number
      of GCNA-1-labeled cells during fetal development when the oocytes progress
      through meiotic prophase. These observations suggest that multiple causes are
      responsible for oocyte elimination.

PMID- 12798293
TI  - Extraretinal and retinal hedgehog signaling sequentially regulate retinal
      differentiation in zebrafish.
AB  - Hedgehog (Hh) signaling is required for eye development in vertebrates; known
      roles in the zebrafish include regulation of eye morphogenesis and ganglion cell
      and photoreceptor differentiation. We employed a temporally selective Hh
      signaling knockdown strategy, by using antisense morpholino oligonucleotides or
      the teratogenic alkaloid cyclopamine, in order to dissect the separate roles of
      Hh signaling arising from specific sources. We also examined the eye phenotype of
      zebrafish slow muscle-omitted (smu) mutants, which lack a functional smoothened
      gene, encoding a component of the Hh signal transduction pathway. We find that Hh
      signaling from extraretinal sources is required for the initiation of retinal
      differentiation, but this involvement may be independent of the effects of Hh
      signaling on optic stalk development. We also find that Hh signals from ganglion
      cells participate in propagating expression of ath5, and we suggest that the
      effects of Hh signals from the retinal pigmented epithelium on photoreceptor
      differentiation may be mediated by the transcription factor rx1.

PMID- 12798294
TI  - Netrins and DCC in the guidance of migrating neural crest-derived cells in the
      developing bowel and pancreas.
AB  - Vagal neural crest-derived precursors of the enteric nervous system colonize the
      bowel by descending within the enteric mesenchyme. Perpendicular secondary
      migration, toward the mucosa and into the pancreas, result, respectively, in the
      formation of submucosal and pancreatic ganglia. We tested the hypothesis that
      netrins guide these secondary migrations. Studies using RT-PCR, in situ
      hybridization, and immunocytochemistry indicated that netrins (netrins-1 and -3
      mice and netrin-2 in chicks) and netrin receptors [deleted in colorectal cancer
      (DCC), neogenin, and the adenosine A2b receptor] are expressed by the fetal
      mucosal epithelium and pancreas. Crest-derived cells expressed DCC, which was
      developmentally regulated. Crest-derived cells migrated out of explants of gut
      toward cocultured cells expressing netrin-1 or toward cocultured explants of
      pancreas. Crest-derived cells also migrated inwardly toward the mucosa of
      cultured rings of bowel. These migrations were specifically blocked by antibodies
      to DCC and by inhibition of protein kinase A, which interferes with DCC
      signaling. Submucosal and pancreatic ganglia were absent at E12.5, E15, and P0 in
      transgenic mice lacking DCC. Netrins also promoted the survival/development of
      enteric crest-derived cells. The formation of submucosal and pancreatic ganglia
      thus involves the attraction of DCC-expressing crest-derived cells by netrins.

PMID- 12798295
TI  - Rodent oocytes express an active adenylyl cyclase required for meiotic arrest.
AB  - The intracellular levels of cAMP play a critical role in the meiotic arrest of
      mammalian oocytes. However, it is debated whether this second messenger is
      produced endogenously by the oocytes or is maintained at levels inhibitory to
      meiotic resumption via diffusion from somatic cells. Here, we demonstrate that
      adenylyl cyclase genes and corresponding proteins are expressed in rodent
      oocytes. The mRNA coding for the AC3 isoform of adenylyl cyclase was detected in
      rat and mouse oocytes by RT-PCR and by in situ hybridization. The expression of
      AC3 protein was confirmed by immunocytochemistry and immunofluorescence analysis
      in oocytes in situ. Cyclic AMP accumulation in denuded oocytes was increased by
      incubation with forskolin, and this stimulation was abolished by increasing
      intraoocyte Ca(2+) with the ionophore A23187. The Ca(2+) effects were reversed by
      an inhibitor of Ca(2+), calmodulin-dependent kinase II. These regulations of cAMP
      levels indicate that the major cyclase that produces cAMP in the rat oocyte has
      properties identical to those of recombinant or endogenous AC3 expressed in
      somatic cells. Furthermore, mouse oocytes deficient in AC3 show signs of a defect
      in meiotic arrest in vivo and accelerated spontaneous maturation in vitro.
      Collectively, these data provide evidence that an adenylyl cyclase is functional
      in rodent oocytes and that its activity is involved in the control of oocyte
      meiotic arrest.

PMID- 12798296
TI  - The Opitz syndrome gene MID1 is essential for establishing asymmetric gene
      expression in Hensen's node.
AB  - Patterning the avian left-right (L/R) body axis involves the establishment of
      asymmetric molecular signals on the left and right sides of Hensen's node. We
      have examined the role of the chick Midline 1 gene, cMid1, in generating
      asymmetric gene expression in the node. cMid1 is initially expressed bilaterally,
      but its expression is then confined to the right side of the node. We show that
      this restriction of cMid1 expression is a result of repression by Shh on the left
      side of the node. Misexpression of cMid1 on the left side of the node results in
      bilateral Bmp4 expression and a loss of Shh expression. Correspondingly,
      downstream left pathway genes are repressed while right pathway genes are
      ectopically activated. Conversely, knocking down endogenous right-sided cMid1
      results in a loss of Bmp4 expression and bilateral Shh expression. This results
      in an absence of right pathway genes and the ectopic activation of the left
      pathway on the right. Here, we present a revised model for the establishment of
      asymmetric gene expression in Hensen's node based on the epistatic interactions
      observed between Shh, cMid1, and Bmp4.

PMID- 12798297
TI  - beta-Catenin signals regulate cell growth and the balance between progenitor cell
      expansion and differentiation in the nervous system.
AB  - beta-Catenin is an essential component of the canonical Wnt signaling system that
      controls decisive steps in development. We employed here two conditional beta
      catenin mutant alleles to alter beta-catenin signaling in the central nervous
      system of mice: one allele to ablate beta-catenin and the second allele to
      express a constitutively active beta-catenin. The tissue mass of the spinal cord
      and brain is reduced after ablation of beta-catenin, and the neuronal precursor
      population is not maintained. In contrast, the spinal cord and brain of mice that
      express activated beta-catenin is much enlarged in mass, and the neuronal
      precursor population is increased in size. beta-Catenin signals are thus
      essential for the maintenance of proliferation of neuronal progenitors,
      controlling the size of the progenitor pool, and impinging on the decision of
      neuronal progenitors to proliferate or to differentiate.

PMID- 12798298
TI  - c-jun regulation and function in the developing hindbrain.
AB  - Hindbrain development is a well-characterised segmentation process in
      vertebrates. The bZip transcription factor MafB/kreisler is specifically
      expressed in rhombomeres (r) 5 and 6 of the developing vertebrate hindbrain and
      is required for proper caudal hindbrain segmentation. Here, we provide evidence
      that the mouse protooncogene c-jun, which encodes a member of the bZip family, is
      coexpressed with MafB in prospective r5 and r6. Analysis of mouse mutants
      suggests that c-jun expression in these territories is dependent on MafB but
      independent of the zinc-finger transcription factor Krox20, another essential
      determinant of r5 development. Loss- and gain-of-function studies, performed in
      mouse and chick embryos, respectively, demonstrate that c-Jun participates,
      together with MafB and Krox20, in the transcriptional activation of the Hoxb3
      gene in r5. The action of c-Jun is likely to be direct, since c-Jun homodimers
      and c-Jun/MafB heterodimers can bind to essential regulatory elements within the
      transcriptional enhancer responsible for Hoxb3 expression in r5. These data
      indicate that c-Jun acts both as a downstream effector and a cofactor of MafB and
      belongs to the complex network of factors governing hindbrain patterning.

PMID- 12798299
TI  - Conservation of the heterochronic regulator Lin-28, its developmental expression
      and microRNA complementary sites.
AB  - The heterochronic gene lin-28 is a regulator of developmental timing in the
      nematode Caenorhabditis elegans. It must be expressed in the first larval stage
      and downregulated by the second stage for normal development. This downregulation
      is mediated in part by lin-4, a 21-nt microRNA. If downregulation fails due to a
      mutation in a short sequence in the lin-28 3' UTR that is complementary to lin-4,
      then a variety of somatic cell lineages fail to progress normally in development.
      Here, we report that Lin-28 homologues exist in diverse animals, including
      Drosophila, Xenopus, mouse, and human. These homologues are characterized by the
      LIN-28 protein's unusual pairing of RNA-binding motifs: a cold shock domain (CSD)
      and a pair of retroviral-type CCHC zinc knuckles. Conservation of LIN-28 proteins
      shows them to be distinct from the other conserved family of CSD-containing
      proteins of animals, the Y-box proteins. Importantly, the LIN-28 proteins of
      Drosophila, Xenopus, and mouse each appear to be expressed and downregulated
      during development, consistent with a conserved role for this regulator of
      developmental timing. In addition, the extremely long 3' UTRs of mouse and human
      Lin-28 genes show extensive regions of sequence identity that contain sites
      complementary to the mammalian homologues of C. elegans lin-4 and let-7
      microRNAs, suggesting that microRNA regulation is a conserved feature of the Lin
      28 gene in diverse animals.

PMID- 12798300
TI  - Specification of cell fates within the salivary gland primordium.
AB  - The Drosophila salivary gland is a simple tubular organ derived from a contiguous
      epithelial primordium, which is established by the activities of the homeodomain
      containing proteins Sex combs reduced (SCR), Extradenticle (EXD), and Homothorax
      (HTH). EGF signaling along the ventral midline specifies the salivary duct fate
      for cells in the center of the primordium, while cells farther away from the
      source of EGF signal adopt a secretory cell fate. EGF signaling works, at least
      in part, by repressing expression of secretory cell genes in the duct primordium,
      including fork head (fkh), which encodes a winged-helix transcription factor.
      FKH, in turn, represses trachealess (trh), a duct-specific gene initially
      expressed throughout the salivary gland primordium. trh encodes a basic helix
      loop-helix PAS-domain containing transcription factor that has been proposed to
      specify the salivary duct fate. In conflict with this model, we find that three
      genes, dead ringer (dri), Serrate (Ser), and trh itself, are expressed in the
      duct independently of trh. Expression of all three duct genes is repressed in the
      secretory cells by FKH. We also show that SER in the duct cells signals to the
      adjacent secretory cells to specify a third cell type, the imaginal ring cells.
      Thus, localized EGF- and Notch-signaling transform a uniform epithelial sheet
      into three distinct cell types. In addition, Ser directs formation of actin rings
      in the salivary duct.

PMID- 12798301
TI  - VegT induces endoderm by a self-limiting mechanism and by changing the competence
      of cells to respond to TGF-beta signals.
AB  - The maternal determinant VegT is required for both endoderm and mesoderm
      formation by the Xenopus embryo. An important downstream mediator of VegT action
      is Xsox17, which has been proposed to be induced in cell-autonomous, then signal
      dependent phases. We show that Xsox17 is a direct VegT target, but that direct
      induction of Xsox17 by VegT is rapidly inhibited. This inhibition is relieved by
      TGF- beta signalling, to which the future endoderm cell is sensitised by VegT,
      resulting in the observed dependence on cell contact for maintained Xsox17
      expression. We propose that this change in regulation is a consequence of a VegT
      induced repressor, inhibiting direct induction of early endoderm markers by VegT,
      and contributing to the formation of the boundary of the endodermal domain.

PMID- 12798302
TI  - Oscillatory CaMKII activity in mouse egg activation.
AB  - Fertilization-induced intracellular calcium (Ca(2+)) oscillations stimulate the
      onset of mammalian development, and little is known about the biochemical
      mechanism by which these Ca(2+) signals are transduced into the events of egg
      activation. This study addresses the hypothesis that transient increases in
      Ca(2+) similar to those at fertilization stimulate oscillatory Ca(2+)/calmodulin
      dependent kinase II (CaMKII) enzyme activity, incrementally driving the events of
      egg activation. Since groups of fertilized eggs normally oscillate
      asynchronously, synchronous oscillatory Ca(2+) signaling with a frequency similar
      to fertilization was experimentally induced in unfertilized mouse eggs by using
      ionomycin and manipulating extracellular calcium. Coanalysis of intracellular
      Ca(2+) levels and CaMKII activity in the same population of eggs demonstrated a
      rapid and transient enzyme response to each increase in Ca(2+). Enzyme activity
      increased 370% during the first Ca(2+) rise, representing about 60% of maximal
      activity, and had decreased to basal levels within 5 min from the time Ca(2+)
      reached its peak value. Single fertilized eggs monitored for Ca(2+) had a mean
      increase in CaMKII activity of 185%. One and two ionomycin-induced Ca(2+)
      transients resulted in 39 and 49% mean cortical granule (CG) loss, respectively,
      while CG exocytosis and resumption of meiosis were inhibited by a CaMKII
      antagonist. These studies demonstrate that changes in the level of Ca(2+) and in
      CaMKII activity can be studied in the same cell and that CaMKII activity is
      exquisitely sensitive to experimentally induced oscillations of Ca(2+) in vivo.
      The data support the hypothesis that CaMKII activity oscillates for a period of
      time after normal fertilization and temporally regulates many events of egg
      activation.

PMID- 12798303
TI  - IL-12-assisted immunization generates CD4+ T cell-mediated immunity to Listeria
      monocytogenes.
AB  - Mice infected with virulent Listeria monocytogenes develop long-lived acquired
      immunity. We previously reported that acquired immunity to Listeria could also be
      elicited by immunizing mice with non-viable Listeria or listerial
      proteins/peptides in combination with IL-12. Here we show that this IL-12
      assisted immunization strategy was effective in class I but not in class II MHC
      deficient mice, suggesting that antigen-specific CD4(+) T cells are selectively
      generated using this adjuvant system. We have also evaluated the importance of
      endogenous production of IFN-gamma and IL-12 for the efficacy of IL-12-assisted
      immunization. IFN-gamma-deficient mice immunized with HKLM and IL-12 failed to
      produce effective Listeria-specific responses. In contrast, IL-12-deficient mice
      were able to generate protective antigen-specific T cell responses in response to
      immunization with HKLM and IL-12, indicating that exogenous IL-12 is sufficient
      to initiate a cytokine cascade that results in a potent T(H)1 response. IL-12
      assisted immunization provides a model in which both the generation and effector
      mechanisms of anti-bacterial antigen-specific CD4(+) effector cells can be
      analyzed.

PMID- 12798304
TI  - Dual expression of CD80 and CD86 produces a tumor vaccine superior to single
      expression of either molecule.
AB  - A murine model for neuroblastoma, Neuro-2a (N2a), was used to establish a model
      tumor vaccine. An aggressive subclone of N2a and the less aggressive parental
      line were transfected with CD80, CD86, or both molecules and stable lines were
      established. The less aggressive N2a expressing either CD80 or CD86 induced anti
      tumor immunity. In contrast, dual expression of CD80 and CD86 was required to
      initiate a protective anti-tumor immune response against the aggressive subclone.
      Control of tumor growth was dependent on CD8+ lymphocytes that infiltrated dual
      expressing (CD80 and CD86) lesions. These tumor-infiltrating lymphocytes (TIL)
      exhibited a non-classical mechanism of tumor cell lysis that may require both the
      up-regulation of cell surface molecules on the tumor and the subsequent lytic
      activity normally associated with CD8+ TIL. Although Fas was up-regulated by the
      tumor in the presence of IFN-gamma, N2a and transfected N2a cell lines were not
      sensitive to Fas-mediated lysis.

PMID- 12798305
TI  - Immunoprotection in proestrus females following trauma-hemorrhage: the pivotal
      role of estrogen receptors.
AB  - Immune responses in proestrus females are not altered after trauma-hemorrhage,
      whereas they are markedly depressed in males. Elevated levels of female sex
      steroids appear to be responsible for maintaining immune responses but it remains
      unknown, whether estrogen per se is responsible. To study this, proestrus female
      C3H/HeN mice were subjected to laparotomy (i.e., soft tissue trauma) and
      hemorrhagic shock (35+/-5 mmHg for 90 min, then resuscitated) or sham operation
      and received the estrogen receptor antagonist EM-800 or vehicle during
      resuscitation. Two hours following trauma-hemorrhage, splenocyte proliferation,
      IL-2, IL-3, IFN-gamma release, and splenic macrophage IL-6 release was maintained
      in vehicle-treated females. In EM-800-treated females, however, these immune
      parameters were significantly depressed. Following trauma-hemorrhage, Kupffer
      cell TNF-alpha release and circulating TNF-alpha were increased only in EM-800
      treated females. These findings indicate that the ability of proestrus females to
      maintain immune function following trauma-hemorrhage is estrogen-dependent and
      mediated via estrogen receptors.

PMID- 12798306
TI  - Human natural killer cell activity against porcine targets: modulation by control
      of the oxidation-reduction environment and role of adhesion molecule
      interactions.
AB  - Xenotransplantation, especially using porcine sources, has been proposed as a
      means to alleviate the shortage of human organs for transplantation. NK cells
      appear to be important mediators of the xenogeneic immune responses, including
      the human anti-pig response. Having previously established the redox regulation
      of NK cell activity against tumor target cells, we now report that the
      interaction of human NK cells with porcine target cells is also regulated by
      redox. Thiol-deprivation strongly diminished the capacity of IL-2-activated human
      NK cells to kill porcine endothelial cells. This inhibition correlated with
      reduced proliferation and interferon (IFN)-gamma production by IL-2-activated NK
      cells. For fresh NK cells, pretreatment with diethyl maleate (DEM), which was
      used to deplete intracellular thiols, reduced lysis of porcine and human targets.
      Because many adhesion molecules exhibit interspecies recognition, we further
      investigated whether changes in expression of adhesion molecules might explain
      our observations. DEM treatment reduced the expression of CD11b and CD29 on fresh
      NK cells. Monoclonal antibody blocking studies showed that the combination of mAb
      to CD11b and CD18 reduced lytic activity against both PAEC as well as K562,
      although other qualitative differences were observed between the porcine and
      human target cells. These findings suggest that the oxidative stress-induced
      downregulation of CD18 may be important in modulating cytotoxic activity of fresh
      NK cells against PAEC and K562 targets through reduced formation of the
      CD11b/CD18 heterodimer. Thus, the appropriate manipulation of redox status may
      provide a means to enhance survival of non-human animal tissues in humans through
      modulation of adhesion molecule expression/interactions.

PMID- 12798307
TI  - A recombinant vector expressing transgenes for four T-cell costimulatory
      molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+ and CD8+ T-cell
      activation, protection from apoptosis, and enhanced cytokine production.
AB  - The role of OX40L on the activation of T cells was investigated using poxvirus
      vectors expressing OX40L alone or in combination with three other T-cell
      costimulatory molecules: B7-1, ICAM-1, and LFA-3. Poxvirus vector-infected cells
      were used to stimulate nai;ve or activated CD4(+) and CD8(+) T cells. These
      studies demonstrate that (a) OX40L plays a role in sustaining the long-term
      proliferation of CD8(+) T cells in addition to the known effect on CD4(+) T cells
      following activation, (b) OX40L enhances the production of Th1 cytokines (IL-2,
      IFN-gamma, and TNF-alpha) from both CD4(+) and CD8(+) while no change in IL-4
      expression was observed, and (c) the anti-apoptotic effect of OX40L on T cells is
      likely the result of sustained expression of anti-apoptotic genes while genes
      involved in apoptosis are inhibited. In addition, these are the first studies to
      demonstrate that the combined use of a vector driving the expression of OX40L
      with three other costimulatory molecules (B7-1, ICAM-1, and LFA-3) both enhances
      initial activation and then further potentiates sustained activation of nai;ve
      and effector T cells.

PMID- 12798308
TI  - Plasma membrane depolarization reduces nitric oxide (NO) production in P388D.1
      macrophage-like cells during Leishmania major infection.
AB  - In the present study, we compare changes in host cell plasma membrane potential
      (V(m)), K(+) fluxes, and NO production during K(+) channel blockade with those
      changes that occur during infection with Leishmania major. Infection of P388D.1
      cells with L. major promastigotes or treatment with K(+) channel blockers (either
      1mM 4-AP, 10mM TEA, or 200 microM quinine) suppressed NO production. Inhibition
      of NO production correlated with depolarization of the P388D.1 cell V(m).
      Infection of P388D.1 cells with L. major increased the unidirectional influx of
      rubidium (86Rb), a tracer for K(+) flux, that was comparable to that induced by
      K(+) channel blockade by 1mM 4-AP. The similar effects of K(+) channel blockers
      and L. major on NO production, K(+) influx, and V(m) suggest that K(+) channel
      activity and the maintenance of V(m) is important for NO production in these
      cells. We suggest that intracellular parasites employ a strategy to inhibit NO
      production by disrupting V(m) during the invasion/infection process by altering
      host cell K(+) channel activity.

PMID- 12798309
TI  - Assessment of cell mediated immunogenicity of Mycobacterium leprae-derived
      antigens.
AB  - The antigenicity of Mycobacterium leprae (M. leprae)-derived cell membrane
      fraction was examined using human dendritic cells (DCs). Immature DCs
      internalized and processed the cell membrane components, and expressed M. leprae
      derived antigens (Ags) on their surface. The expression of MHC class II, CD86,
      and CD83 Ags on DCs and CD40 ligand (L)-associated IL-12 p70 production from DCs
      were up-regulated by the membrane Ags. Moreover these stimulated DCs induced
      significantly higher level of interferon-gamma (IFN-gamma) production by
      autologous CD4(+) and CD8(+) T cells than those pulsed with equivalent doses of
      live M. leprae or its cytosol fraction. Both subsets of T cells from tuberculoid
      leprosy patients also produced several fold more IFN-gamma than those from normal
      individuals. Furthermore, the intracellular perforin production in CD8(+) T cells
      was up-regulated in an Ag-dose dependent manner. These results suggest that M.
      leprae membrane Ags might be useful as the vaccinating agents against leprosy.

PMID- 12798310
TI  - Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from
      old mice.
AB  - There are fewer bone marrow Pre-B cells in old compared to young mice. We have
      demonstrated both decreased rearrangement of the V to DJ IgH gene segments and
      low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B
      cells, from old compared to young mice. However, there was no difference in the
      level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent
      with the prior reports that fewer bone marrow emigrants enter the peripheral B
      cell populations of old than young mice, we identified fewer transitional B cells
      in the blood, as well as the spleen, of old than young mice. Association of
      impaired IgH rearrangement with a decreased number of transitional B cells in old
      mice was supported by finding that the percentage and number of transitional B
      cells expressing rearranged IgH and IgL transgenes, which do not require
      rearrangement of their endogenous IgH gene segments, were comparable in old and
      young mice. In contrast, the percentage and number of transitional B cells in
      these Ig-transgenic mice, which escaped allelic exclusion and have rearranged
      endogenous IgH gene segments, showed an age-associated decline similar to that
      seen in wild type mice. These data are consistent with the view that impaired V
      to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B
      cells as well as the decreased levels of transitional B cells in the periphery.

PMID- 12798312
TI  - Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate
      carboxypeptidase II.
AB  - A series of hydroxamic acids has been prepared as potential inhibitors of
      glutamate carboxypeptidase II (GCP II). Compounds based on a P1' residue (primed
      side inhibitors) were more potent than those based on a P1 group (unprimed-side
      inhibitors). Inhibitory potency of the primed-side GCP II inhibitors was found to
      be dependent on the number of methylene units between the hydroxamate group and
      pentanedioic acid. Succinyl hydroxamic acid derivative, 2
      (hydroxycarbamoylmethyl)pentanedioic acid, is the most potent GCP II inhibitor
      with an IC(50) value of 220nM. The comparison of the results to those of other
      classes of GCP II inhibitors as well as hydroxamate-based MMP inhibitors provides
      further insight into the structure-activity relationships of GCP II inhibition.

PMID- 12798313
TI  - Novel inhibitors of procollagen C-terminal proteinase. Part 1: diamino Acid
      hydroxamates.
AB  - The parallel synthesis of novel inhibitors of procollagen C-terminal proteinase
      is described. The synthetic strategy allowed for the facile synthesis of a large
      number of side-chain diversified diamino acid hydroxamates, of which the D
      diaminopropionic acid derivatives were shown to be single digit nanomolar PCP
      inhibitors.

PMID- 12798314
TI  - A low background high-throughput screening (HTS) fluorescence assay for lipases
      and esterases using acyloxymethylethers of umbelliferone.
AB  - Esters and acyloxymethyl ethers of umbelliferone were evaluated as fluorogenic
      substrates for lipases and esterases with respect to stability and resistance to
      non-specific hydrolysis. Isobutyryloxymethyl ether 1c and pivaloxymethyl ether 1d
      were found to be optimal substrates for enzyme assays, particularly with respect
      to HTS applications.

PMID- 12798316
TI  - 2,4-Dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists: further
      characterization of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4
      (1,2,2-trimethyl-propyl) ester and structure-activity relationships.
AB  - Following the disclosure of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl
      ester 4-(1,2,2-trimethyl-propyl) ester [3,5-dimethyl PPP] as a potent and
      selective mGluR1 non-competitive antagonist, we report here further in vivo
      characterization of this important tool and disclose the investigation of the C-5
      position, which led to very potent compounds.

PMID- 12798315
TI  - Structural features of piperazinyl-linked ciprofloxacin dimers required for
      activity against drug-resistant strains of Staphylococcus aureus.
AB  - We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess
      potent antibacterial activity against drug-resistant strains of Staphylococcus
      aureus. In this study, we report the preparation and evaluation of a series of
      incomplete dimers toward ascertaining structural features of piperazinyl-linked
      ciprofloxacin dimers that render these agents refractory to fluoroquinolone
      resistance mechanisms in Staphylococcus aureus.

PMID- 12798317
TI  - BR96 conjugates of highly potent anthracyclines.
AB  - The 6-maleimidocaproylhydrazone derivatives of highly potent antitumor agents 5
      Diacetoxypentyldoxorubicin and Morpholinodoxorubicin were synthesized and
      conjugated to monoclonal antibody BR96 and control IgG. Immunoconjugate molar
      ratios were generally 7.5-8.5, and dimer aggregate levels were low. The linkers
      released parent drug at lysosomal pH 5, while they remained stable at neutral pH.
      BR96 conjugates were highly potent and antigen specific in vitro. The BR96-DAPDOX
      conjugate demonstrated an IC(50) of 0.03 micrometer and was at least 300-fold
      more potent than a non-binding IgG-DAPDOX control conjugate.

PMID- 12798318
TI  - Synthesis of the novel liqustrazine derivatives and Their protective effect on
      injured vascular endothelial cell damaged by hydrogen peroxide.
AB  - A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was
      designed and synthesized. Most compounds were found to be 1.5-4.5-fold higher
      potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal
      vascular endothelial cells and in protecting against hyperoxic acute injury. The
      most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation
      rate (P(max)) of 88.57% at the concentration of 0.1 mmol L(-1). Structure
      activity relationships of these compounds were discussed.

PMID- 12798319
TI  - Total synthesis of a biotinylated derivative of phorboxazole A via sonogashira
      coupling.
AB  - The C46 terminus of phorboxazole A has been modified to incorporate a biotin
      terminated linker via direct palladium-mediated Sonogashira reaction conditions.
      Synthetic 45,46-dehydrobromophorboxazole A was joined with a tris
      (polyethyleneglycol)vinyl iodide-biotin ester using catalytic PdCl(2)(PPh(3))(2),
      CuI, and Et(3)N in THF. This process demonstrates the utility of mild carbon
      carbon bond formation in the context of phorboxazoles' architecture and provides
      a potential affinity probe.

PMID- 12798320
TI  - A new class of histamine H(3)-receptor antagonists: synthesis and structure
      activity relationships of 7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolines.
AB  - The synthesis and biological evaluation of novel cycloheptaquinoline antagonists
      of the human H(3) receptor are described. Two series of compounds, bearing either
      an amino substituent or an alkyne linker at the 11-position, were investigated.
      Modifications of the amino substituents, optimization of chain length and the
      effect of conformational restraints are described. Several compounds with high
      affinity and selectivity for the H(3) receptor were discovered.

PMID- 12798321
TI  - Nicotinyl aspartyl ketones as inhibitors of caspase-3.
AB  - Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its
      inhibition may have an important impact in the treatment of several degenerative
      diseases. Since P(1) aspartic acid is a required element of recognition for this
      enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase
      chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was
      identified to be an inhibitor of caspase-3. Substitution at the 5-position of the
      pyridine ring and conversion of the aldehyde to ketones led to a series of potent
      inhibitors of caspase-3.

PMID- 12798322
TI  - Fundamental structure-activity relationships associated with a new structural
      class of respiratory syncytial virus inhibitor.
AB  - Structure-activity relationships surrounding the dialkylamino side chain of a
      series of benzotriazole-derived inhibitors of respiratory syncytial virus fusion
      based on the screening lead 1a were examined. The results indicate that the
      topology of the side chain is important but the terminus element offers
      considerable latitude to modulate physical properties.

PMID- 12798323
TI  - Molecular design, synthesis, and structure-Activity relationships leading to the
      potent and selective p56(lck) inhibitor BMS-243117.
AB  - A series of structurally novel benzothiazole based small molecule inhibitors of
      p56(lck) were prepared to elucidate their structure-activity relationships
      (SARs), selectivity and cell activity in the T-cell proliferation assay. BMS
      243117 (compound 2) is identified as a potent, and selective Lck inhibitor with
      good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.

PMID- 12798325
TI  - (+/-)-2-(3-Piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific
      bradycardic agents.
AB  - A series of (+/-)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines were prepared
      and their bradycardic activities were examined in isolated guinea-pigs' right
      atria and in anesthetized rats. Modifications on the benzyl moiety of the parent
      compound, 1, led to the identification of compound 11e as a potent and specific
      bradycardic agent.

PMID- 12798324
TI  - Bivalent biogenic amine reuptake inhibitors.
AB  - A series of aryltropane-based bivalent ligands was prepared and investigated for
      binding potency and for their ability to inhibit reuptake of human dopamine,
      serotonin and norepinephrine transporters. The bivalent ligand 4, comprised of
      linking an aryltropane by an octamethylene spacer showed high efficacy for the
      human dopamine transporter and had a discrimination ratio of 130.

PMID- 12798326
TI  - Structure-activity relationships of novel anti-malarial agents. Part 7: N-(3
      benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides with
      polar moieties.
AB  - In a previous report, we have provided evidence that novel anti-malarial
      compounds based on 2,5-diaminobenzophenone farnesyltransferase inhibitors might
      benefit from the presence of a polar moiety at the para position of the terminal
      phenyl of the arylfurylacryloyl partial structure. Here, we demonstrate that
      different moieties with hydrogen bond acceptor properties lead to equipotent or
      even improved anti-malarial activity in comparison to the nitro group described
      before.

PMID- 12798327
TI  - Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial
      activity.
AB  - FR900098 represents an improved derivative of the new antimalarial drug
      fosmidomycin and acts through inhibition of the 1-deoxy-D-xylulose 5-phosphate
      (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent
      pathway of isoprenoid biosynthesis. Prodrugs with increased activity after oral
      administration were obtained by chemical modification of the phosphonate moiety
      to yield acyloxyalkyl esters. The most successful compound demonstrated 2-fold
      increased activity in mice infected with the rodent malaria parasite Plasmodium
      vinckei.

PMID- 12798328
TI  - Muscarinic M(3) receptor antagonists with (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2
      hydroxyphenylacetamide Structures. Part 2.
AB  - Optimization of the amine part of our original muscarinic M(3) receptor
      antagonist 1 was performed to identify M(3) receptor antagonists that are
      superior to 1. Compounds carrying a variety of diamine moieties without
      hydrophobic substituent on the nitrogen atom were screened against the binding
      affinity for the M(3) receptor and the selectivity for M(3) over the M(1) and
      M(2) receptors. This process led to a 4-aminopiperidinamide (2l) with a K(i)
      value of 5.1 nM and with a selectivity of the M(3) receptor that was 46-fold
      greater than that of the M(2) receptor. Further derivatization of 2l by inserting
      a spacer group or by incorporating alkyl group(s) into the amine part resulted in
      the identification of an 4-(aminoethyl)piperidinamide 2l-b with a K(i) value of
      3.7 nM for the M(3) receptor and a selectivity for the M(3) receptor that was 170
      fold greater than that of the M(2) receptor.

PMID- 12798329
TI  - Potent Grb2-SH2 domain antagonists not relying on phosphotyrosine mimics.
AB  - Development of Grb2-SH2 domain antagonists is an effective approach to inhibit
      the growth of malignant cells by modulating Grb2-related Ras signaling. We report
      here potent Grb2-SH2 domain antagonists that do not rely on phosphotyrosine or
      its mimics. These non-phosphorylated antagonists were developed and further
      modified by constraining the backbone conformation and optimizing amino acid side
      chains of a phage library-derived peptide, G1TE. After extensive SAR studies and
      structural optimization, non-phosphorylated peptide 12 was discovered with an
      IC(50) of 75 nM. This potent peptidomimetic provides a novel template for the
      development of non-pTyr containing Grb2-SH2 domain antagonists and acts as a
      chemotherapeutic lead for the treatment of erbB2-related cancer.

PMID- 12798330
TI  - N-(4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl, butenyl and
      butynyl)arylcarboxamides as novel dopamine D(3) receptor antagonists.
AB  - The dopamine D(3) receptor subtype has been targeted as a potential neurochemical
      modulator of the behavioral actions of psychomotor stimulants, such as cocaine.
      Previous synthetic studies provided structural requirements for high affinity
      binding to D(3) receptors which included a 2,3-dichloro-phenylpiperazine linked
      to an arylamido function via a butyl chain. To reduce lipophilicity of these
      agents and further investigate optimal conformation, a second series of 15 novel
      ligands was designed that included heteroaromatic substitution and unsaturated
      alkyl linkers. These compounds were synthesized and evaluated for binding at rat
      D(3) and D(2) receptors stably expressed in Sf9 cells. D(3) binding affinities
      ranged from K(i)=0.6-1080 nM, with a broad range of D(3)/D(2) selectivities (2
      97). The discovery of potent, selective and bioavailable D(3) receptor ligands
      will provide essential molecular probes to elucidate the role D(3) receptors play
      in the psychomotor stimulant and reinforcing effects of cocaine.

PMID- 12798331
TI  - 3-Azido-3-deoxy-glycopyranoside derivatives as scaffolds for the synthesis of
      carbohydrate-based universal pharmacophore mapping libraries.
AB  - The regiospecific syntheses of six monosaccharide scaffolds, 1-6, containing a
      carboxylic acid, an azido and a free hydroxyl group were accomplished through the
      utilization of a key intermediate, namely, methyl 3-azido-3-deoxy-beta-D
      glucopyranoside (10). Scaffold 2 was also used in generating combinatorial
      libraries using solid-phase methodologies.

PMID- 12798332
TI  - Cyclic amine sulfonamides as linkers in the design and synthesis of novel human
      beta(3) adrenergic receptor agonists.
AB  - Piperidine, pyrrolidine, and azetidine sulfonamides were examined as linkers in
      designing novel human beta(3) adrenergic receptor (beta(3)-AR) agonists. The
      azetidine derivative 37, and piperidine derivatives 7, 8, and 13 were found to be
      potent beta(3)-AR agonists and have good selectivity against beta(1)- and beta(2)
      AR.

PMID- 12798333
TI  - Structure-activity study of novel tricyclic benzazepine arginine vasopressin
      antagonists.
AB  - Novel tricyclic benzazepine derivatives were synthesized as arginine vasopressin
      (AVP) antagonists. Several tricyclic compounds showed potent antagonistic
      activity in rat AVP receptors V(1a) and V(2). Derivatives containing pyrrolo
      tricyclic amines, 13i-k, 30, and 31 also showed selectivity for the V(2)
      receptor.

PMID- 12798334
TI  - High-affinity thrombin receptor (PAR-1) ligands: a new generation of indole-based
      peptide mimetic antagonists with a basic amine at the C-terminus.
AB  - A new generation of indole-based peptide mimetics, bearing a basic amine at the C
      terminus, was developed by the agency of two complementary, multistep, trityl
      resin-based approaches. Thus, we obtained several high-affinity thrombin receptor
      (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR
      1 with excellent affinity (IC(50)=25 and 35 nM, respectively) and to effectively
      block platelet aggregation induced by SFLLRN-NH(2) (TRAP-6) and alpha-thrombin.

PMID- 12798335
TI  - 6-Alkyl, alkoxy, or alkylthio-substituted 3-(4-methanesulfonylphenyl)-4
      phenylpyran-2-ones: a novel class of diarylheterocyclic selective cyclooxygenase
      2 inhibitors.
AB  - A novel class of 3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones possessing a
      central six-membered lactone (pyran-2-one) ring system, in conjunction with C-6
      alkyl (Me, Et or i-Pr), alkoxy (OMe, OEt or O-i-Pr), and alkylthio (SMe, SEt or S
      i-Pr) substituents, were designed for evaluation as selective COX-2 inhibitors.

PMID- 12798336
TI  - 4-Amino-2-(aryl)-butylbenzamides and Their conformationally constrained
      analogues. Potent antagonists of the human neurokinin-2 (NK(2)) receptor.
AB  - A library, evaluating a range of piperazines, piperidines and acyclic amines, as
      replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was
      prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue
      (2a) which was further optimised using classical single-compound synthesis to
      yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained
      analogues of (2j), generally offered no potency advantage in this particular
      series.

PMID- 12798337
TI  - Synthesis of radiolabeled biphenylsulfonamide matrix metalloproteinase inhibitors
      as new potential PET cancer imaging agents.
AB  - Novel matrix metalloproteinase (MMP) inhibitor radiotracers, (S)-3-methyl-2
      (2',3',4'-methoxybiphenyl-4-sulfonylamino)-butyric acid [(11)C]methyl ester (1a
      c), (S)-3-methyl-2-(2',3',4'-fluorobiphenyl-4-sulfonylamino)-butyric acid
      [(11)C]methyl ester (1d-f), and (S)-3-methyl-2-(4'-nitrobiphenyl-4-sulfonylamino)
      butyric acid [(11)C]methyl ester (1g), a series of substituted
      biphenylsulfonamide derivatives, have been synthesized for evaluation as new
      potential positron emission tomography (PET) cancer imaging agents.

PMID- 12798339
TI  - Synthesis and in vitro activity of new methylenepiperidinyl and
      methylenepyrrolidinyl oxazolidinone antibacterial agents.
AB  - We have prepared and evaluated the antibacterial activities of a series of
      substituted methylenepiperidinyl and methylenepyrrolidinyl oxazolidinones against
      several gram-positive strains including the resistant strains of Staphyloccus and
      Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed comparable or
      superior in vitro activities (MIC) to vancomycin.

PMID- 12798338
TI  - Antitumor agents. Part 218: Cappamensin A, a new In vitro anticancer principle,
      from Capparis sikkimensis.
AB  - A new inhibitor of in vitro tumor cell replication, cappamensin A (1) (2H-1,4
      benzoxazin-3(4H)-one, 6-methoxy-2-methyl-4-carbaldehyde), was isolated from the
      roots of Capparis sikkimensis subsp. formosana using bioactivity-guided
      fractionation. The structure of 1 was established by spectroscopic methods,
      including 2D NMR analyses. Compound 1 displayed significant in vitro anticancer
      activity against ovarian (1A9), lung (A549), ileocecal (HCT-8), breast (MCF-7),
      nasopharyngeal (KB), and vincristine resistant (KB-VIN) human tumor cell lines
      with ED(50) values </=4 microgram/mL (mean GI(50) value of 15.1 microM).

PMID- 12798340
TI  - Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA
      synthetase inhibitors.
AB  - Starting with a micromolar lead identified from high-throughput screening, a
      series of pyrazoles were discovered with significantly improved potency on
      bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA
      synthetase.

PMID- 12798341
TI  - Borrelidin induces the transcription of amino acid biosynthetic enzymes via a
      GCN4-dependent pathway.
AB  - Global cellular profiling of messenger RNA levels has been used to provide
      insight into the effects of the angiogenesis inhibitor borrelidin on the
      eukaryotic model organism Saccharomyces cerevisiae. The most notable result of
      treatment with borrelidin is the induction of amino acid biosynthetic enzymes in
      a time-dependent fashion. We have ascertained that induction of this pathway
      involves the GCN4 transcription factor. This conclusion was determined by
      treating a yeast strain lacking this gene and observing the absence of increased
      gene transcription under Gcn4p control.

PMID- 12798342
TI  - Enantiotracin.
AB  - The enantiomer of the antibiotic bacitracin A was prepared by solid-phase total
      synthesis. ent-Bacitracin A was found to be equally potent to the natural
      enantiomer in in vitro susceptibility assays. This supports the notion that
      bacitracin exerts its antibacterial effects through interaction with
      bactoprenylpyrophosphate, an achiral ligand.

PMID- 12798343
TI  - Osteoblasts: novel roles in orchestration of skeletal architecture.
AB  - Osteoblasts are located on bone surfaces and are the cells responsible for bone
      formation through secretion of the organic components of bone matrix. Osteoblasts
      are derived from mesenchymal osteoprogenitor cells found in bone marrow and
      periosteum. Following a period of secretory activity, osteoblasts undergo either
      apoptosis or terminal differentiation to form osteocytes surrounded by bone
      matrix. Osteoblasts secrete a characteristic mixture of extracellular matrix
      proteins including type I collagen as the major component as well as
      proteoglycans, glycoproteins and gamma-carboxylated proteins. Cells of the
      osteoblast lineage also provide factors essential for differentiation of
      osteoclasts (bone-resorbing cells). By regulating osteoclast differentiation and
      activity in response to systemic influences, osteoblasts not only play a central
      role in regulation of skeletal architecture, but also in calcium homeostasis.
      Inadequate osteoblastic bone formation in relation to osteoclastic resorption
      results in osteoporosis, a disease characterised by enhanced skeletal fragility.
      Cellfacts: Osteoblasts are the cells responsible for bone formation. Osteoblasts
      indirectly control levels of bone resorption. Osteoblasts play a key role in the
      pathophysiology of osteoporosis and the resulting fractures, which constitute a
      major public health burden in developed countries.

PMID- 12798344
TI  - Liver failure: basis of benefit of therapy with the molecular adsorbents
      recirculating system.
AB  - Accumulation of albumin-bound toxins is known to occur in liver failure, and to
      variable extents is responsible for the associated end-organ dysfunctions
      (kidney, circulation, brain). The toxin-binding and scavenging functions of
      albumin are exploited in albumin dialysis for removal of these toxins. The
      extracorporeal liver support device known as molecular adsorbents recirculating
      system (MARS) is based on dialysis across an albumin-impregnated membrane, using
      20% albumin as dialysate. Charcoal and anion exchange resin columns in the
      circuit help cleanse and regenerate the dialysate. Clinical studies over the last
      few years have demonstrated proven reduction in hyperbilirubinaemia, along with
      an improvement in encephalopathy, systemic haemodynamics and renal function in
      liver failure patients, as well as apparent improvement in survival. The results
      of larger controlled clinical trials, as well as studies investigating the
      pathophysiological basis of its effect, are awaited.

PMID- 12798345
TI  - Hyperinsulinism in infancy: understanding the pathophysiology.
AB  - Hyperinsulinism in infancy (HI) is the commonest cause of persistent and
      recurrent hypoglycaemia in the infancy and childhood period. HI is a
      heterogeneous disorder with respect to clinical presentation, histology,
      molecular biology and genetics. Recent advances have provided unique insights
      into the pathophysiology of this intriguing disease as well as providing an
      understanding of the normal physiological and biochemical mechanisms regulating
      insulin secretion from pancreatic beta-cells. The histological differentiation of
      focal and diffuse forms of HI has radically changed the surgical management to
      this disease. So far mutations in five different genes have been described which
      lead to dysregulated insulin secretion from beta-cells. Despite these advances
      the genetic defect is still unknown in about 60% of cases.

PMID- 12798346
TI  - Natriuretic peptides--a class of heterologous molecules in plants.
AB  - Immunological and physiological evidence suggests the presence of biologically
      active natriuretic peptide hormones (NPs) in plants. Evidence includes specific
      binding of rat atrial NP, [rANP (99-126)] to plant membranes and the promotion of
      cyclic guanosine-3',5'-monophosphate (cGMP) mediated stomatal responses.
      Furthermore, anti-ANP affinity purifies biologically active plant immunoreactants
      (irPNPs) and a biologically active Arabidopsis thaliana irPNP (AtPNP-A) has been
      identified. AtPNP-A belongs to a novel class of molecules that share some
      similarity with the cell wall loosening expansins but do not contain the
      carbohydrate-binding wall anchor, thus suggesting that irPNPs and ANP are
      heterologues. We hypothesise that irPNP-like molecules have evolved from
      primitive glucanase-like molecules that have been recruited to become
      systemically mobile modulators of homeostasis acting via the plasma membrane.
      Such a function is compatible with localisation in the conductive tissue and the
      physiological and cellular modes of action of irPNPs reported to-date.

PMID- 12798347
TI  - Regulation of osteogenic proteins by chondrocytes.
AB  - The purpose of this review is to summarize the current scientific knowledge of
      bone morphogenetic proteins (BMPs) in adult articular cartilage. We specifically
      focus on adult cartilage, since one of the major potential applications of the
      members of the BMP family may be a repair of adult tissue after trauma and/or
      disease. After reviewing cartilage physiology and BMPs, we analyze the data on
      the role of recombinant BMPs as anabolic agents in tissue formation and
      restoration in different in vitro and in vivo models following with the
      endogenous expression of BMPs and factors that regulate their expression. We also
      discuss recent transgenic modifications of BMP genes and subsequent effect on
      cartilage matrix synthesis. We found that the most studied BMPs in adult
      articular cartilage are BMP-7 and BMP-2 as well as transforming growth factor
      beta (TGF-beta). There are a number of contradicting reports for some of these
      growth factors, since different models, animals, doses, time points, culture
      conditions and devices were used. However, regardless of the experimental
      conditions, only BMP-7 or osteogenic protein-1 (OP-1) exhibits the most
      convincing effects. It is the only BMP studied thus far in adult cartilage that
      demonstrates strong anabolic activity in vitro and in vivo with and without
      serum. OP-1 stimulates the synthesis of the majority of cartilage extracellular
      matrix proteins in adult articular chondrocytes derived from different species
      and of different age. OP-1 counteracts the degenerative effect of numerous
      catabolic mediators; it is also expressed in adult human, bovine, rabbit and goat
      articular cartilage. This review reveals the importance of the exploration of the
      BMPs in the cartilage field and highlights their significance for clinical
      applications in the treatment of cartilage-related diseases.

PMID- 12798348
TI  - Molecular pathogenesis of subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) results from leakage of blood into the
      subarachnoid space and carries high morbidity and mortality. However, there is
      limited understanding to date, of the risk factors, cellular, intermediate
      biochemical and genetic traits predisposing to SAH. Nevertheless, in conjunction
      with improved methods of diagnostic imaging and less invasive approaches to
      preventing aneurysmal rupture, there may be utility in gaining a better
      understanding of the pathogenesis and in identifying pre-disease markers.
      Additionally, it is not impossible that drugs of value (e.g. matrix or
      endothelial modifiers) could become available. Several different clinical
      subtypes can be recognised, distinguished by arterial or venous involvement,
      presence of unruptured arterial aneurysms, and apparently "sporadic" and
      "familial" occurrences. Epidemiological risk factors include alcohol consumption
      and smoking: hypertension is a risk factor for rupture. About 10% seem to reflect
      strong family history and this subset may be particularly illuminating with
      respect to the molecular pathogenesis. Haemodynamic stress and poor vascular
      structure may be the main mechanisms of pathogenesis. The epidemiological and
      statistical evidence for familial megaphenic genes and modifier genes is
      reviewed. This review focuses on the pathogenesis, as opposed to inflammatory
      response to SAH. It sets in context the roles of specific genes and their protein
      products, such as polycystin (PKD1), fibrillin (FBN1), collagen III (COL3A1),
      elastin (ELN), collagen IV, protease inhibitor or alpha1-antitrypsin (PI) and
      proteases. These considerations illustrate the shortfalls in current knowledge,
      the needs of future biochemical and cellular research and their potential
      implications for future prevention of this often fatal condition.

PMID- 12798349
TI  - Regulation of proximal tubular epithelial cell CD44-mediated binding and
      internalisation of hyaluronan.
AB  - BACKGROUND: Increased expression of the connective tissue polysaccharide
      hyaluronan (HA) in the renal corticointerstitium is associated with progressive
      renal fibrosis. Numerous studies have demonstrated involvement proximal tubular
      epithelial cells in the fibrotic process and in the current study we have
      characterised their expression of the HA receptor, CD44, and examined changes in
      CD44 expression and function in response to either IL-1beta or glucose. METHODS:
      Characterisation of CD44 splice variant expression was carried out in primary
      cultures of human proximal tubular cells (PTC) and HK2 cells. Binding and
      internalisation HA was examined by addition of exogenous of fluorescein-HA (fl
      HA), and expression of CD44 examined by immunoblot analysis and flow cytometry.
      Alteration in "functional" CD44 was determined by immunoprecipitation of CD44
      following stimulation in the presence of fl-HA. RESULTS: PTC, both primary
      culture and the PTC cell line, HK2, express at least 5 CD44 splice variants, the
      expression of which are not altered by addition of either IL-1beta or 25mM D
      glucose. Addition of either stimulus increased cell surface binding and
      internalisation of fl-HA and increased expression of functionally active CD44.
      Increased binding and internalisation of fl-HA, was blocked by anti-CD44
      antibody, and by the inhibition of O-glycosylation. CONCLUSIONS: The data
      demonstrate that stimuli inducing PTC HA synthesis also regulate PTC-HA
      interactions. Furthermore increased HA binding and internalisation is the result
      of post-translational modification of CD44 by O-glycosylation, rather than by
      alteration in expression of CD44 at the cell surface, or by alternate use of CD44
      splice variants.

PMID- 12798350
TI  - Low molecular weight phosphotyrosine protein phosphatase from PC12 cells.
      Purification, some properties and expression during neurogenesis in vitro and in
      vivo.
AB  - The purification and partial characterization of low molecular weight
      phosphotyrosine phosphatase (LMW-PTP) was reported for the first time in PC12
      cells. In addition, the expression levels during neuronal phenotype induction by
      nerve growth factor (NGF) and during neurogenesis in chick embryos were
      investigated. LMW-PTP was purified to homogeneity and showed a single band of
      about 18 kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis. A
      native molecular mass of 20.1 kDa was determined by gel filtration on Sephadex G
      75 column. The LMW-PTP from PC12 cells displays structural and biochemical
      characteristics similar to the enzyme isolated for normal tissues. It was
      specifically immunoprecipitated by an affinity purified antibody directed against
      the bovine liver enzyme. The enzyme is present in the cytosolic and cytoskeletal
      cell compartment where is tyrosine phosphorylated. Time course expression of LMW
      PTP in PC12 cells was investigated after NGF treatment and showed an increase of
      about 30% in the basal level of LMW-PTP from 0 to 72 h. These changes were
      related to the appearance in PC12 cells of neuronal processes and to a decrease
      in cell proliferation. An increase of the LMW-PTP expression was also observed in
      vivo during chick embryo neurogenesis from 8-day-old embryos to adult chicks. The
      protein level, assayed by immunoblotting, increases from 14-day-old embryos to
      the hatched chicks reaching the adult levels within the first week after birth.
      These data indicate that the neurogenesis process is accompanied by a
      physiological increment of LMW-PTP expression in vitro and in vivo.

PMID- 12798351
TI  - Expression of spermidine/spermine N1-acetyltransferase in HeLa cells is regulated
      by amino acid sufficiency.
AB  - The effect of amino acids on the regulation of the expression of
      spermidine/spermine N(1)-acetyltransferase (SSAT), the key enzyme of polyamine
      catabolism, was studied in HeLa cells. When compared with similar exposure to
      complete medium, deprivation of arginine, methionine or leucine gave rise to a
      time-dependent, slowly reversible increase in the cellular level of SSAT mRNA
      that started to be significant after 8, 12 or 16h and reached four-, five- and
      two-fold after 16h, respectively. Experiments utilizing (i) constructs containing
      fragments of the SSAT promoter linked to a luciferase reporter gene or (ii)
      actinomycin D (Act-D)-treated cells indicated that the increase in the SSAT mRNA
      level was due to an augmentation in gene transcription and message stability
      after omission of one of the polyamine precursor amino acids. By contrast, SSAT
      mRNA stabilisation was only observed when leucine was the omitted amino acid.
      Amino acid deprivation was also found to cause increased intracellular activity
      of SSAT concurrent with changes in the cell polyamine content, namely increased
      putrescine but decreased spermine levels. Furthermore, stable expression of a
      dominant negative mutant of stress-activated protein kinase/extracellular signal
      regulated protein kinase (SAPK/ERK) kinase 1 in HeLa cells was found to inhibit
      the increase in SSAT mRNA by amino acid deprivation. The data suggest that c-Jun
      N-terminal kinase/SAPK (JNK/SAPK) may be involved in the amino acid-dependent
      regulation of SSAT expression.

PMID- 12798352
TI  - Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in
      prostate cancer cells.
AB  - 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) and its derivatives are a
      potential treatment of human prostate cancer. The antiproliferative action of
      1alpha,25(OH)(2)D(3) is mainly exerted through nuclear vitamin D receptor (VDR)
      mediated control of target gene transcription. To explore the target genes which
      are regulated by 1alpha,25(OH)(2)D(3) in human prostate cancer LNCaP cells, cDNA
      microarray was performed by using a chip that contains 3000 gene probes. The
      results showed that 24 genes were regulated by 1alpha,25(OH)(2)D(3). Five of them
      encode proteins which belong to metabolic enzymes and fatty acid biosynthesis.
      Fatty acid synthase (FAS) was found to be down-regulated by 1alpha,25(OH)(2)D(3),
      and the regulation was confirmed by real-time quantitative RT-PCR analysis.
      Inhibition of FAS expression by 1alpha,25(OH)(2)D(3) in LNCaP cells was more than
      50% at 6h. Inhibitory effect of 1alpha,25(OH)(2)D(3) on FAS expression was
      completely blocked in the presence of protein synthesis inhibitor cycloheximide,
      indicating that the down-regulation of FAS gene expression by
      1alpha,25(OH)(2)D(3) was indirect in LNCaP cells. An inhibition of FAS activity
      by cerulenin resulted in a strong inhibition of LNCaP cell proliferation. The
      inhibition of FAS expression and cell proliferation by 1alpha,25(OH)(2)D(3)
      seemed to be androgen-dependent, since antiandrogen, casodex and DCC-treatment of
      serum blocked the vitamin D action. The findings suggest that FAS is involved in
      the antiproliferative effect of 1alpha,25(OH)(2)D(3) in presence of androgens on
      prostate cancer LNCaP cells.

PMID- 12798353
TI  - Membrane-initiated steroid signaling (MISS): genomic steroid action starts at the
      plasma membrane.
AB  - Plasma membrane (PM) steroid recognition sites are thought to be responsible only
      for rapid, non-genomic responses without any link to the nuclear receptor
      mediated genomic effects of steroids. We focused on a PM "glucocorticoid
      importer" (GC-importer) that imports GC into rat liver cells. This site interacts
      also with particular gestagens (progesterone, P; medroxyprogesterone, MP;
      ethynodiol, Ethy) and estrogens (ethinylestradiol, EE(2); mestranol), which do
      not bind to the nuclear GC receptor (GR). To elucidate the role of the GC
      importer, we transfected a rat wild-type hepatocyte (CC-1) and a hepatoma cell
      line, unable to import GC (MH 3924), with a GC<-->GR-responsive luciferase (luc)
      reporter gene. Selected steroids were tested for their ability to induce or
      inhibit luc expression. Corticosterone (B) and dexamethasone (Dex), but also the
      GC-antagonists cortexolone (Cortex), P and MP, induced luc. Even the PM
      impermeable BSA-derivatives of B, Dex and Cortex did so to almost the same extent
      as the free steroids. MH 3924 cells respond stronger than CC-1 to luc inducing
      steroids. Luc expression was inhibited by RU 38 486, but also by EE(2) and Ethy.
      The thiol reactive mesylate-derivatives of B, Dex and Cortex induced to a
      considerably lesser extent than the free or BSA-steroids. The thiol reagent
      mersalyl blocks cellular entry of GC and inhibits luc induction in CC-1 cells.
      Incubation with EE(2) and B of PM-vesicles, isolated from liver cells, resulted
      in a decrease of the density of two 75 and 52kDa G-proteins reflecting a
      diminished exchange of GDP by GTP. CONCLUSION: the PM-residing GC-importer, now
      renamed "Steroid Hormone Recognition and Effector Complex" (SHREC) is an
      interdependent part of the complete GC signal propagation in which G-proteins are
      involved. Free SH-groups of SHREC are a prerequisite for genomic GC activity.
      Specific interactions between SHREC and GC-agonist/-antagonist trigger steroid
      dependent signaling. However, import of the ligand into the cell terminates it.
      Thus, the PM-related non-genomic steroid responses are clearly linked to the GR
      related genomic effects.

PMID- 12798354
TI  - Regulation of progesterone receptor isoforms expression by sex steroids in the
      rat lung.
AB  - In this work, we determined the expression pattern and the hormonal regulation of
      progesterone receptor (PR) isoforms in the rat lung of ovariectomized female rats
      after estradiol (E2) and progesterone (P4) treatments. We also evaluated the
      content of estrogen receptor beta (ER-beta) which is the ER isoform expressed in
      the lung. RNA and proteins were extracted and processed for reverse transcription
      (RT) coupled to polymerase chain reaction (PCR) and Western blot, respectively.
      The expression of both PR isoforms in the lung at mRNA and at protein levels was
      up-regulated by E2 while P4 down-regulated it at mRNA level. P4 did not modify PR
      isoforms protein content unlike its effect in the uterus where both PR isoforms
      were down-regulated by their ligand at mRNA and protein levels. PR-A was the
      predominant isoform, both in the lung and in the uterus. In the lung, ER-beta was
      down-regulated by E2 while P4 did not significantly modify the effect of E2.
      These results suggest that both PR isoforms should be expressed in the rat lung,
      and that their expression should be differentially regulated at mRNA and at
      protein levels by P4. We also suggest that the up-regulation of PR isoforms by E2
      in the lung is mediated by ER-beta.

PMID- 12798355
TI  - Studies on the development of resistance to the pure antiestrogen Faslodex in
      three human breast cancer cell lines.
AB  - In order to understand the mechanisms underlying the development of resistance to
      a pure antiestrogen we established three human breast carcinoma cell lines
      resistant to ZM 182780 (ZM) (Faslodex). Long-term cultivation of the ERalpha
      positive, 17beta-estradiol (E(2))-responsive cell lines T47D, ZR-75-1, and MCF-7
      with the pure antiestrogen ZM 182780 resulted in the T47D-r, ZR-75-1-r, and MCF-7
      r cell lines, which proliferate continuously in the presence of 10(-6)M ZM
      182780. The resulting antiestrogen-resistant cells grow equally well in medium
      with or without E(2) and in medium with or without ZM 182780 indicating that they
      are no longer estrogen-responsive. ERalpha expression was lost at the protein
      level in all three resistant cell lines. At the mRNA level, the ERalpha was only
      faintly detectable in T47D-r, whereas a weak signal was seen in ZR-75-1-r and MCF
      7-r. By reverse transcription-polymerase chain reaction (RT-PCR) the ERbeta was
      detectable in the antiestrogen-sensitive and -resistant breast cancer cell lines,
      however, ZR75-1-r contained the smallest signal for ERbeta. In all three
      antiestrogen-resistant cells the PR was undetectable, whereas binding of
      epidermal growth factor (EGF) and protein expression of epidermal growth factor
      receptor (EGFR) were increased. To analyse alterations in the gene expression
      pattern in more detail Atlas arrays were hybridised with RNA isolated from T47D-r
      and T47D and the two Ca2+-binding proteins calgranulin A and B were found to be
      up-regulated in T47D-r compared to T47D. Calgranulin A and B were also both up
      regulated in ZR-75-1-r and MCF-7-r compared to their antiestrogen-sensitive
      counterparts. Loss of ERalpha expression may be linked to the acquisition of
      antiestrogen resistance and enhanced expression of the EGFR and of proteins of
      the S100 family of Ca2+-binding proteins which may contribute to the outgrowth of
      resistant cells.

PMID- 12798356
TI  - Molecular cloning and characterization of 3beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4 isomerase cDNAs from Japanese eel ovary.
AB  - 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) is a
      crucial steroidogenic enzyme which catalyzes an essential step in the
      biosynthesis of all classes of steroid hormones. Two closely related cDNAs,
      encoding Japanese eel ovarian types I and II 3beta-HSD, were cloned and
      characterized. Both cDNAs putatively encoded 375 amino acid residues sharing high
      sequence homology with those of rainbow trout (71%) and mammalian (approximately
      45-50%) 3beta-HSD. Transient expression of types I and II 3beta-HSD in COS-7
      cells revealed that both proteins possess 3beta-hydroxysteroid dehydrogenase as
      well as Delta(5)-Delta(4) isomerase activity for both pregnenolone and
      dehydroepiandrosterone, with the preference of pregnenolone over
      dehydroepiandrosterone as substrate, although the type I protein is more active
      than the type II. By northern blot analysis, a single band of the 3beta-HSD
      transcript of approximately 1.5kb in length was observed in ovarian tissue and
      the total transcript abundance of both 3beta-HSDs remained constant throughout
      ovarian development artificially induced by gonadotropin-rich salmon pituitary
      homogenate. This lack of change in 3beta-HSD transcript abundance during ovarian
      development did not correlate with the fluctuation of its enzymatic activity
      reported previously, which may suggest that changes in 3beta-HSD activity during
      ovarian development may be, in part, post-transcriptionally regulated in the
      Japanese eel ovary.

PMID- 12798357
TI  - The detection of 20S-hydroxycholesterol in extracts of rat brains and human
      placenta by a gas chromatograph/mass spectrometry technique.
AB  - The presence of 20(S)-hydroxycholesterol in rat brains and human placenta has
      been established using the gas chromatography/mass spectrometry (GC/MS) select
      ion monitoring (SIM) technique. Identification was ensured by three criteria: the
      specific retention time when the compound emerges from the gas chromatogram and
      the two m/z ions (201 and 461amu) which are characteristic of its mass spectrum.
      The possible role of 20(S)-hydroxycholesterol in steroid hormone biosynthesis and
      in other biological processes is discussed.

PMID- 12798358
TI  - Concurrent corticosteroid and phenanthrene transformation by filamentous fungus
      Cunninghamella elegans.
AB  - A filamentous fungus Cunninghamella elegans IM 1785/21Gp which displays ability
      of 17alpha,21-dihydroxy-4-pregnene-3,20-dione (cortexolone) 11-hydroxylation
      (yielding epihydrocortisone (eF) and hydrocortisone (F)) and polycyclic aromatic
      hydrocarbons (PAHs) degradation, was used as a microbial eucaryotic model to
      study the relationships between mammalian steroid hydroxylation and PAHs
      metabolization. The obtained results showed faster transformation of phenanthrene
      in Sabouraud medium supplemented with steroid substrate (cortexolone).
      Simultaneously phenanthrene stimulated epihydrocortisone production from
      cortexolone. In phenanthrene presence the ratio between cortexolone hydroxylation
      products (hydrocortisone and epihydrocortisone) was changed from 1:5.1-6.2 to
      1:7.6-8.4 in the culture without phenanthrene. Cytochrome P-450 content
      significantly increased after the culture supplementation by the second
      substrate, phenanthrene or cortexolone, adequately. To confirm the involvement of
      cytochrome P-450 in phenanthrene metabolism, the inhibition studies were
      performed. The cytochrome P-450 inhibitors SKF 525-A (1.5mM) and 2-methyl-1,2-di
      3-pyridyl-1-propanone (metyrapone) (2mM) inhibited phenanthrene transformation by
      80 and 62%, respectively. 1-aminobenzotriazole (1mM) completely blocked
      phenanthrene metabolism. The obtained results suggest a presence of connections
      between steroid hydroxylases and enzymes involved in PAH degradation in C.
      elegans.

PMID- 12798359
TI  - Induction of endogenous genes by peroxisome proliferator activated receptor alpha
      ligands in a human kidney cell line and in vivo.
AB  - The peroxisome proliferator activated receptor alpha (PPARalpha) plays a key role
      in regulating fatty acid metabolism by regulating expression of genes involved in
      fatty acid oxidation. To identify endogenous transcripts that could be used as
      surrogate markers for on-target activity of PPARalpha agonists, we employed a
      global profiling approach using DNA microarrays. The HK-2 cell line derived from
      proximal tubules of the human kidney, showed induction of several genes,
      including pyruvate dehydrogenase kinase 4 (PDK-4) and adipocyte differentiation
      related protein (ADRP) by PPARalpha ligands. HK-2 cells express detectable levels
      of PPARalpha and its dimerization partner the retinoid X receptor (RXRalpha)
      proteins. Induction of PDK-4 in these cells correlates with induction of PDK-4 in
      the liver of fat-fed hamsters. The magnitude of fibrate induction of PDK-4 in the
      liver also mirrors the decrease in serum triglyceride levels. Thus, induction of
      PDK-4 by PPARalpha agonists in the HK-2 cell model closely correlates with its
      induction in vivo and may represent an early marker for PPARalpha agonist action.

PMID- 12798360
TI  - Rat glomerulosa cells in primary culture and E. coli lipopolysaccharide action.
AB  - During endotoxic shock there is a dysfunction of the adrenal gland; both
      corticosterone and aldosterone secretion are altered. The aim of the present
      study is to use glomerulosa cells in primary culture as a target of
      lipopolysaccharide (LPS) action. Glomerulosa cells cultured in basal conditions
      are able to proliferate; bFGF and ACTH have antagonic effects, bFGF increases
      proliferation whereas ACTH is antimitogenic. LPS has a biphasic effect, in the
      short term it is antimitogenic and in the long term increases the proliferation
      rate. LPS inhibits ACTH-induced corticosterone secretion in a dose-dependent
      manner in glomerulosa cells in culture similar to that in fasciculata cells, but
      it does not exert an important direct effect on aldosterone secretion. These
      results show that LPS exerts different effects in ACTH and ANG II signal
      transduction pathways and in the two enzymes which catalyze the late step in the
      steroidogenesis, 11beta-hydroxylase and aldosterone synthase, which could be in
      agreement with the existence of both enzymes, regulated independently, in rat
      zona glomerulosa cells.

PMID- 12798361
TI  - 3 beta-hydroxysteroid dehydrogenase isomerase (3beta-HSD) activity in the rat
      sciatic nerve: kinetic analysis and regulation by steroids.
AB  - We have shown that progesterone (PROG) has a stimulatory effect on myelin
      formation after sciatic nerve injury. PROG is synthesized from pregnenolone
      (PREG) by the enzyme 3 beta-hydroxysteroid dehydrogenase isomerase (3beta-HSD).
      At the occasion of the 15th International Symposium of the Journal of the Steroid
      Biochemistry and Molecular Biology, we presented some of our recent results
      demonstrating, expression and activity of the enzyme 3beta-HSD in the rat sciatic
      nerve. We determined the kinetic properties of 3beta-HSD and its regulation by
      PROG and estradiol. The expression of 3beta-HSD protein was assessed by Western
      blot analysis, and the 3beta-HSD activity was evaluated by incubating homogenates
      with [3H]-PREG as substrate and NAD(+) as cofactor. Levels of steroids formed
      were calculated either by extrapolation of the relationship between the tritiated
      peaks obtained by thin layer chromatography (TLC) and the initial amount of PREG,
      or by gas chromatography-mass spectrometry (GC-MS) determination. A rapid
      increase in PROG formation was found between 0 and 50min of incubation and no
      significant change was observed between 1 and 4h. The calculated K(m) value was
      close to the values obtained for the 3beta-HSD types I and IV isoforms.
      Trilostane caused a potent inhibition of the rate of conversion of PREG to PROG.
      When we tested the effects of progesterone and estradiol on 3beta-HSD activity, a
      significant inhibition was obtained.

PMID- 12798362
TI  - Lysozyme from the gut of the soft tick Ornithodoros moubata: the sequence,
      phylogeny and post-feeding regulation.
AB  - Sequence of a tick gut lysozyme (TGL) from the soft tick Ornithodoros moubata was
      determined by cloning and sequencing of overlapping polymerase chain reaction
      (PCR) and RACE PCR products. It is the first lysozyme sequence representing the
      subphylum Chelicerata. The resulting open reading frame codes for a putative
      signal peptide of 22 amino-acid residues and a mature protein composed of 124
      amino-acids. Calculated mass of the protein is 14037.75 Da and a theoretical
      isoelectric point is 8.16. The phylogenetic analysis revealed that the TGL
      belongs to the c-type lysozymes. It forms a distinct monophyletic group together
      with multiple lysozyme-like sequences found in the gene products agCP6542 from
      Anopheles gambiae strain PEST and CG8492-PA from Drosophila melanogaster. This
      group is referred to as an H-branch due to a unique histidine residue at position
      52 which replaces the highly conserved tyrosine present in the vast majority of c
      type lysozymes. TGL seems to be an interesting case in which the features of
      lysozymes with anti-bacterial and digestive function are combined. Semi
      quantitative RT-PCR and Northern blotting analysis demonstrated that TGL is
      strongly up-regulated at the transcriptional level after a bloodmeal. The maximum
      lysozyme mRNA level was detected 16 h post bloodmeal and the message remained
      stable for 5 days and then it slowly dropped down to the level of non-fed ticks
      within 2 weeks.

PMID- 12798363
TI  - Hemocyte production and maturation in an invertebrate animal; proliferation and
      gene expression in hematopoietic stem cells of Pacifastacus leniusculus.
AB  - Regulation of hematopoiesis in invertebrates is largely unknown, although the
      hemocytes are essential in immunity, performing functions such as phagocytosis,
      encapsulation and lysis of foreign cells. We have developed a method to isolate
      hematopoietic stem cells from the freshwater crayfish, Pacifastacus leniusculus,
      and therefore, this animal provides a powerful tool for studies on invertebrate
      hematopoiesis. The hematopoietic tissue of crayfish was found to be actively
      proliferating. Injection of a beta1,3-glucan caused a severe loss of hemocytes,
      followed by a rapid recovery, due to release from the hematopoietic organ.
      Transcripts for peroxinectin, a hemocyte cell adhesion protein, were present in
      the hematopoietic cells, whereas mRNA for proPO was not detected. A gene coding
      for a Runt-domain protein known to be involved in hematopoiesis in Drosophila and
      mammals, was upregulated prior to hemocyte release.We conclude that hemocytes are
      synthesised and partly differentiated in the hematopoietic tissue, but the final
      differentiation into functional hemocytes expressing proPO is not completed until
      the hemocytes are released into the circulation.

PMID- 12798364
TI  - A single amphioxus and sea urchin runt-gene suggests that runt-gene duplications
      occurred in early chordate evolution.
AB  - Runt-homologous molecules are characterized by their DNA binding runt-domain
      which is highly conserved within bilaterians. The three mammalian runt-genes are
      master regulators in cartilage/bone formation and hematopoiesis. Historically
      these features evolved in Craniota and might have been promoted by runt-gene
      duplication events. The purpose of this study was therefore to investigate how
      many runt-genes exist in the stem species of chordates, by analyzing the number
      of runt-genes in what is likely to be the closest living relative of Craniota
      amphioxus. To acquire further insight into the possible role of runt-genes in
      early chordate evolution we have determined the number of runt-genes in sea
      urchins and have analyzed the runt-expression pattern in this species. Our
      findings demonstrate the presence of a single runt-gene in amphioxus and sea
      urchin, which makes it highly likely that the stem species of chordates harbored
      only a single runt-gene. This suggests that runt-gene duplications occurred later
      in chordate phylogeny, and are possibly also associated with the evolution of
      features such as hematopoiesis, cartilage and bone development. In sea urchin
      embryos runt-expression involves cells of endodermal, mesodermal and ectodermal
      origin. This complex pattern of expression might reflect the multiple roles
      played by runt-genes in mammals. A strong runt-signal in the gastrointestinal
      tract of the sea urchin is in line with runt-expression in the intestine of
      nematodes and in the murine gastrointestinal tract, and seems to be one of the
      phylogenetically ancient runt-expression domains.

PMID- 12798365
TI  - A toll-like receptor (TLR) gene that is up-regulated in activated goldfish
      macrophages.
AB  - An expressed sequence tag screen of a macrophage activation factor and
      lipopolysaccharide (LPS) stimulated goldfish macrophage subtractive library
      generated several transcripts of a putative teleost homologue of the toll-like
      receptor (TLR) family. The full-length TLR cDNA was sequenced and is predicted to
      encode a type I transmembrane protein with an extracellular domain containing
      leucine rich repeats and a cytoplasmic tail encoding a toll/interleukin-1
      receptor domain. These findings indicate that the gene identified is the first
      teleost homologue of the TLR family reported. Constitutive expression of TLR was
      observed in unstimulated macrophages and was also observed in goldfish spleen and
      kidney but not in heart and liver tissues. A significant up-regulation of the TLR
      mRNA in cultured macrophages following treatments with each of bacterial LPS,
      heat-killed Aeromonas salmonicida, and live Mycobacterium chelonei was observed
      after 3 and 6 h post-stimulation, though with different kinetics from each other.
      A relative decline in TLR expression was observed after 24 h, but expression
      levels were still higher than that of unstimulated cells. Thus pathogen-derived
      factors appear to differentially modulate the expression of TLR in goldfish
      macrophages, which undoubtedly contributes to the orchestration and/or induction
      of functional immune responses in fish.

PMID- 12798366
TI  - Channel catfish NK-like cells are armed with IgM via a putative FcmicroR.
AB  - Two-color flow cytometry demonstrated that 4-8% of channel catfish PBL are
      positive for both F and G IgL chain isotypes, suggesting that they passively
      acquire serum IgM via a putative FcmicroR. These cells show spontaneous killing
      toward allogeneic targets, and in vitro stimulation of PBL with allogeneic cells
      results in an increase of double IgL chain positive cells with a concomitant
      increase in nonspecific cytotoxicity. Long-term cultures of alloantigen
      stimulated PBL contain both sIgM(+) and sIgM(-) cytotoxic cells that transcribe
      message for the catfish homolog of the FcepsilonR gamma chain, but not for
      Igmicro and TCR-alpha,-beta, or -gamma chains. Immunoprecipitation of lysates
      from sIgM(+) NK-like cells with anti-IgM co-immunoprecipitated a putative
      FcmicroR of approximately 64 kDa. Finally, removal of IgM from sIgM(+) NK-like
      cells and replacement with anti-hapten antibody enabled antibody-armed effectors
      to kill haptenated targets that were refractory to killing by effectors armed
      with normal IgM. This is the first report suggesting that teleost NK-like cells
      express a putative FcmicroR which participates in antibody-dependent cell
      mediated cytotoxicity.

PMID- 12798367
TI  - Ontogeny of Xenopus NK cells in the absence of MHC class I antigens.
AB  - This paper explores the ontogeny of NK cells in control and early-thymectomized
      (Tx) Xenopus laevis through phenotypic analysis of cells expressing the NK cell
      antigen 1F8 and by performing in vitro cytotoxic assays. Dual color flow
      cytometry reveals that a few 1F8positive splenocytes first emerge in late larval
      life, at approximately 7-weeks post-fertilization. This is about 2-weeks after
      the time when surface MHC class Ia expression can first be detected. The
      proportion of splenocytes expressing 1F8 remains very low in 3-4 month-old
      froglets, but by 1 year there is a sizeable 1F8positive population, which is
      proportionally elevated in Tx frogs. The ontogeny of NK cell function is
      monitored by a 5 h DNA fragmentation (JAM) assay. Control and Tx larval
      splenocytes (from either 5- or 7-week-old tadpoles) fail to kill MHC-deficient
      thymus-derived tumor cell targets. Such in vitro killing is still relatively poor
      in 3-4 month froglets, compared with high levels of tumor cell cytotoxicity
      mediated by splenocytes from older frogs. Immunoprecipitation studies identify
      that the major ligand for the 1F8 mAb is a 55 kDa polypeptide. Finally, further
      evidence is provided that 1F8positive lymphocytes are indeed bona fide NK cells,
      distinct from T cells, since purified 1F8positive splenocytes from Tx Xenopus
      fail to express fully rearranged TCRbeta V region transcripts. We conclude that
      NK cells fail to develop prior to MHC class I protein expression and, therefore,
      do not contribute to the larval immune system, whereas they do provide an
      important backup for T cells in the adult frog by contributing to anti-tumor
      immunity.

PMID- 12798368
TI  - Signaling FcRgamma and TCRzeta subunit homologs in the amphibian Xenopus laevis.
AB  - The genes encoding FcRgamma and TCRzeta homologs were identified using a
      bioinformatic approach in the amphibian Xenopus laevis. Deduced amino acid
      sequence of Xenopus TCRzeta is highly similar to the mammalian and avian
      counterparts, whereas that of FcRgamma differs by the presence of an additional
      ITAM-like motif. The presence of the negatively charged residue in the
      transmembrane regions of both subunits suggests their ability to serve as signal
      transducing modules in complex with activating receptors. The short extracellular
      regions contain characteristic cysteine residues responsible for dimerization in
      the mammalian subunits. According to Southern blot analysis, Xenopus laevis may
      possess two non-allelic genes for each subunit. Northern blots revealed FcRgamma
      transcripts of two sizes differentially expressed in thymus, spleen, intestine,
      liver and kidney. TCRzeta mRNA was predominantly expressed in the thymus and
      spleen. These data indicate that the amphibian immune system employs activating
      receptor complexes arranged in a mammalian-like way.

PMID- 12798369
TI  - Contrasting changes of sensitivity by lymphocytes and neutrophils to mercury in
      developing grey seals.
AB  - Mercury is the principal metal contaminant in the St Lawrence Estuary. It impairs
      humoral, cellular and non-specific immune responses in many species. Since the
      immune system of juvenile seals is immature, it should react differently to the
      effects of contamination compared to that of mature animals. Phagocytosis and
      lymphoblastic transformation responses have been evaluated in the peripheral
      blood leukocytes of eight juvenile grey seals at different intervals of time over
      11 weeks. Dose-response curves of 10(-9)-10(-3)M of methylmercury chloride have
      also been performed in vitro for evaluation of these two immune functions. The
      immune response of grey seals differs during their development. The phagocytosis
      response increased from the 2nd to 5th week post-weaning and then reached a
      plateau. As for the lymphoblastic transformation response, it was stable from the
      2nd to the 3rd week post-weaning, increased significantly at week 4 post-weaning
      and then reached a plateau. These data suggest that these animals should be
      particularly vulnerable to infections, diseases and parasites before the 5th week
      post-weaning. Furthermore, mercury decreased the immune response, and age of
      seals had an effect on cell sensitivity to mercury. Concentrations of 10(-5)M of
      methylmercury chloride decreased phagocytosis and lymphoblastic transformation
      responses. Phagocytosis is more affected by MeHgCl contamination before this
      immune function reaches complete development which occurs at week 5 post-weaning.
      On the other hand, lymphoblastic transformation is more affected by this
      contaminant after its complete development which occurs at week 4 post-weaning.

PMID- 12798370
TI  - Calcium and phosphorus concentrations and the calcium/phosphorus ratio in
      trabecular bone from the femoral neck of healthy humans as determined by neutron
      activation analysis.
AB  - The Ca and P concentrations as well as the Ca/P ratio were estimated in intact
      trabecular bone samples from the femoral neck of healthy humans, 34 women and 44
      men, aged from 15 to 55 years, using instrumental neutron activation analysis.
      The mean values (M+/-SD) for the investigated parameters (on a dry-weight basis)
      were: 12.1+/-3.0%, 5.94+/-1.71%, 2.07+/-0.25 and 10.9+/-2.5%, 5.30+/-1.23%,
      2.07+/-0.22 for females and males, respectively. A statistically significant
      (p</=0.05) decrease of Ca concentration with age was found only for males while
      the P concentration and the Ca/P ratio were not affected by age. No statistically
      significant sex-related differences were observed in any of the parameters. The
      mean values for Ca, P and the Ca/P ratio lay close to the median of the very wide
      range of published data. The individual variation for the Ca/P ratio in
      trabecular bone from the healthy human femoral neck was lower than those for Ca
      and P separately. This suggests that the specificity of the Ca/P ratio is better
      than that of Ca and P concentrations and may be more reliable for the diagnosis
      of bone disorders.

PMID- 12798371
TI  - Development of a low-energy monoenergetic neutron source for applications in low
      dose radiobiological and radiochemical research.
AB  - The McMaster University 3 MV KN Van de Graff accelerator facility primarily
      dedicated to in vivo neutron activation measurements has been used to produce
      moderate dose rates of monoenergetic fast neutrons of energy ranging from 150 to
      600 keV with a small energy spread of about 25 keV (1sigma width of Gaussian) by
      bombarding thin lithium targets with 2.00-2.40 MeV protons. The calculated dose
      rate of the monoenergetic neutrons produced using thin lithium targets as
      functions of beam energy, target thickness, lab angle relative to beam direction,
      and the solid angle subtended by the sample with the target has also been
      reported.

PMID- 12798372
TI  - Optimization of low activity spectrometric gamma-gamma probes for ash
      determination in coal stockpiles.
AB  - A stockpile probe based on backscattered gamma-gamma-ray technique was tested for
      the determination of coal ash. A centralized tool employing a gamma-ray source of
      very low radioactivity (1.85 MBq) was used. This logging tool was tested using
      137Cs and 133 Ba sources with a 37 mm (diameter) by 75 mm NaI (TI) scintillation
      detector. Ten source-detector configurations were analyzed using 137Cs, and
      another nine source-detector configurations are analyzed, using 133Ba source,
      both for four geophysical models, having a borehole diameter of 90 mm. Regression
      analysis on the laboratory logging data for each studied configuration was
      carried out in order to establish calibration equations for ash prediction. The
      optimum configuration for the logging stockpile probe using 137Cs source was
      determined to be 80 mm source to detector spacing, and 80 mm iron thickness
      shielding. This configuration gives the best results for ash prediction. The root
      mean square (rms) deviation for ash is 1.52%. The optimum configuration for the
      logging stockpile probe using 133 Ba source is determined to be 85 mm source to
      detector spacing, and 50mm iron thickness shielding. This configuration gives the
      best results for ash prediction, where the rms deviation for ash is 1.47%.

PMID- 12798373
TI  - Bacteriophages as viral indicators for radiation processing of water: a chemical
      approach.
AB  - Inactivation of the bacteriophages PHI X 174 (somatic coliphage), MS2 (F-specific
      coliphage) and B40-8 (phage infecting Bacteroides fragilis) suspended in tap
      water was studied applying gamma and electron beam irradiation as well. PHI X 174
      phage was found to be a suitable viral indicator for water disinfection by means
      of ionizing radiation. The nutrient broths introduced simultaneously with the
      bacteriophages into the water when it is spiked with the phages for the
      experiments did not significantly change the scavenging capacity of the water
      matrix. No dose rate effect was observed with MS2 and B40-8 phages but PHI X 174
      phage showed a clear dose rate effect. It was found that in water MS2 phage is
      significantly more sensitive to ionizing radiation than Escherichia coli.

PMID- 12798374
TI  - Improved synthesis of anti-[18F]FACBC: improved preparation of labeling precursor
      and automated radiosynthesis.
AB  - The non-natural amino acid anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid
      (FACBC) has shown promise for tumor imaging with positron emission tomography. An
      improved synthesis of the precursor of anti-[18F]FACBC has been devised which
      demonstrates high stereoselectivity and suitability for large-scale preparations.
      An automated radiosynthesis has been developed which provides anti-[18F]FACBC in
      24% decay-corrected yield. Additionally, the major non-radioactive species
      present in doses of anti-[18F]FACBC has been identified as anti-1-amino-3
      hydroxycyclobutane-1-carboxylic acid. Together, these results are important steps
      towards the routine production of anti-[18F]FACBC for human use.

PMID- 12798375
TI  - Optimization of a convenient route to produce N-succinimidyl 4-radiodobenzoate
      for radioiodination of proteins.
AB  - The preparation of N-succinimidyl-4-[131I]iodobenzoate (SIB) has been optimized
      using an alternative technique employing Cu(I)-assisted radioiododebromination
      that produces p-[131I]iodobenzoic acid. The reaction conditions were optimized
      and radiochemical purity of more than 90% was obtained when using 160 degrees C,
      60 min reaction time and a [CuCl]/[p-bromobenzoic acid] relation of about 10(-2).
      After purification, the p-[131I]iodobenzoic acid reacted with TSTU to produce the
      SIB in a radiochemical yield greater than 98%. Protein conjugation using SIB
      resulted in a relatively low radiochemical yield. Biological distribution studies
      evidenced the in vivo stability of the labeled protein.

PMID- 12798376
TI  - Tritium labelling and characterization of the potent imidazoline I1 receptor
      antagonist [5,7-3H] (+/-)-efaroxan at high specific activity.
AB  - (+/-)-Efaroxan 1 is a selective antagonist at the imidazoline I1 receptor. [3H]
      (+/-)-Efaroxan was required to explore its mechanism of action via receptor
      binding assay, and the radioligand was prepared by means of catalytic
      dehalogenation of a dibrominated precursor with tritium.

PMID- 12798377
TI  - Electrochemical radiofluorination. Part 2. Anodic monofluorination of substituted
      benzenes using [18F]fluoride.
AB  - Electrochemical fluorination of various monosubstituted aromatic compounds was
      performed with [18F]fluoride using potentiostatic anodic oxidation on platinum
      electrodes in an undivided cell in acetonitrile with a mixture of
      Et(3)N.3HF/Et(3)N.HCl as electrolyte. Maximum radiochemical yields were obtained
      after a charge of 50C passed the solution. The results showed a clear dependence
      of the radiochemical yields on the oxidation potentials E(1/2) of the substrates
      as a consequence of different substituents namely CH(3)CO-, F-, Cl-, Br- and
      tert.-Butyl. With increasing E(1/2), the fluorination yields decreased from 7.9%
      (tert.-butylbenzene) to 1.5% (acetophenone). The ratio between F-for-X
      substitution and F-for-H substitution correlated with the bond energies of the C
      X bond. With higher bond energies, less X-substitution was observed.

PMID- 12798378
TI  - Fully automated synthesis of O-(3-[18F]fluoropropyl)-L-tyrosine by direct
      nucleophilic exchange on a quaternary 4-aminopyridinium resin.
AB  - A fully automated synthesis of O-(3-[18F]fluoropropyl)-L-tyrosine (FPT), an amino
      acid tracer for tumor imaging with positron emission tomography, is described.
      FPT was prepared by a two-step reaction sequence. Direct nucleophilic
      fluorination substitution of [18F]fluoride with 1,3-di(4
      methylphenylsulfonyloxy)propane on a quaternary 4-(4-methylpiperidinyl)pyridinium
      functionalized polystyrene anion exchange resin, followed by [18F]fluoro-1-(4
      methylphenylsulfonyloxy)propane yielded FPT. The overall radiochemical yield with
      no decay correction was about 12%; the whole synthesis time was about 52 min, and
      the radiochemical purity was above 95%.

PMID- 12798379
TI  - Advantages and limitations of thermal and epithermal neutron activation analysis
      of bulk samples.
AB  - Systematic investigations have been carried out to extend the thermal neutron
      activation method for elemental analysis of bulk samples. A new method developed
      for the determination of the flux perturbation factor renders the thermal and
      epithermal neutron activation analyses of bulky samples of unknown compositions
      possible both in hydrogenous and in graphite moderators. The flux perturbation,
      F, depression, H, and self-absorption, G, factors are given for different
      samples. The limitation of the epithermal neutron activation analysis for
      hydrogenous bulky samples is also discussed.

PMID- 12798380
TI  - Application of decision trees to the analysis of soil radon data for earthquake
      prediction.
AB  - Different regression methods have been used to predict radon concentration in
      soil gas on the basis of environmental data, i.e. barometric pressure, soil
      temperature, air temperature and rainfall. Analyses of the radon data from three
      stations in the Krsko basin, Slovenia, have shown that model trees outperform
      other regression methods. A model has been built which predicts radon
      concentration with a correlation of 0.8, provided it is influenced only by the
      environmental parameters. In periods with seismic activity this correlation is
      much lower. This decrease in predictive accuracy appears 1-7 days before
      earthquakes with local magnitude 0.8-3.3.

PMID- 12798381
TI  - Efficiency transfer in the calibration of a coaxial p-type HpGe detector using
      the Monte Carlo method.
AB  - Monte Carlo simulation was applied to the efficiency transfer exercise described
      in the EUROMET428 project (Appl. Radiat. Isot. 55 (2001) 493), evaluating the
      peak efficiencies in the energy range 60-2000 keV for a typical coaxial p-type
      HpGe detector and several types of source configuration: point sources located at
      various distances from the detector and a cylindrical box containing three
      matrices. The efficiency values were derived in two ways: (a) by direct
      calculation taking into account the physical dimensions of the detector provided
      by the supplier, and (b) by means of relative computation (efficiency transfer)
      taking also into consideration the known efficiency values for a reference point
      source. As expected, some significant discrepancies between the calculated and
      experimental values were found when a direct computation was made using the data
      provided by the supplier. On the contrary, the results for the peak efficiency
      derived by relative calculation by means of an efficiency transfer were in good
      agreement with the experimental values. The deviations found with this last
      procedure were generally below 5% for all the geometries considered, which is
      entirely satisfactory for the purposes of routine measurements.

PMID- 12798382
TI  - The effect of various cations and pH on the adsorption of U(VI) on Amberlite IR
      118H resin.
AB  - The effects of various metal cations and pH on the adsorption of uranium(VI) on
      strongly acidic cation exchanger Amberlite IR-118H (AIR-118H) were studied. The
      metal cations suppress U(VI) adsorption differently depending on their ionic
      radii. Adsorption of U(VI) on AIR-118H peaks at pH 3.4, which was attributed to
      the occurrence of different forms of U(VI) at different pH values. The adsorption
      data were then processed using the Frumkin-Fowler-Guggenheim equation, and the
      standard free energy of adsorption was calculated.

PMID- 12798383
TI  - Thin sintered Al2O3 pellets as thermoluminescent dosimeters for the therapeutic
      dose range.
AB  - Thermoluminescent properties of sintered alumina pellets were investigated with
      the aim of using them as radiation dosimeters. Peak temperatures, signal
      reproducibility, fading, curves of the response to X-radiation, as well as energy
      and angular dependences were studied. The results show that the pellets can be
      used in quality control programs in the therapeutic dose range.

PMID- 12798384
TI  - Cross-section measurements for (n, 2n), (n, p) and (n, n'alpha) reactions on
      gallium isotopes in the neutron energy range of 13.5-14.6 MeV.
AB  - Cross-sections for (n, 2n), (n, p) and (n, n'alpha) reactions have been measured
      on gallium isotopes at the neutron energies of 13.5-14.6MeV using the activation
      technique. Data are reported for the following reactions: 69Ga(n, 2n) 68Ga,
      69Ga(n, p) 69mZn, 71Ga(n, p) (71m)Zn, and 71Ga(n, n'alpha) 67Cu. The neutron
      fluences were determined using the monitor reaction 93Nb(n, 2n) 92mNb.

PMID- 12798385
TI  - Diffusion cooling of thermal neutrons in basic rock minerals by Monte Carlo
      simulation of the pulsed neutron experiments.
AB  - The pulsed neutron experiment (the variable geometric buckling experiment) in
      spherical geometry has been simulated using the MCNP code. The time decay of the
      thermal neutron flux has been observed as a function of the sample size. The
      thermal neutron diffusion cooling coefficient C with the correction F has been
      determined for three basic rock minerals (quartz, calcite, dolomite) at the given
      specific densities. The corresponding density-removed parameters have also been
      obtained.

PMID- 12798386
TI  - Novel map descriptors for characterization of toxic effects in proteomics maps.
AB  - We consider a novel numerical characterization of proteomics maps based on the
      construction of a graph obtained by connecting all protein spots in a proteomics
      map that are at distance equal to, or smaller than, a critical distance D(c). We
      refer to the so constructed graph as a cluster graph and we calculate four
      associated characteristic matrices, previously considered in the literature: (1)
      the Euclidean-distance matrix ED; (2) the neighborhood-distance matrix ND; (3)
      the path-distance matrix based on the shortest paths between connected spots PD;
      and (4) the quotient matrix Q, the elements of which are given as the quotient of
      the corresponding elements of ED and ND matrices. Numerical descriptors for
      proteomics maps include in particular the leading eigenvalue of the Q matrix and
      the family of associated "higher order" matrices defined as powers of Q. These
      map descriptors show considerable sensitivity to perturbations of proteomics maps
      by toxicants.

PMID- 12798387
TI  - Insertion of X-ray structures of proteins in membranes.
AB  - Few structures of membrane proteins are known and their relationships with the
      membrane are unclear. In a previous report, 20 X-ray structures of transmembrane
      proteins were analyzed in silico for their orientation in a 36A-thick membrane
      [J. Mol. Graph. Model. 20 (2001) 235]. In this paper, we use the same approach to
      analyze how the insertion of the X-ray structures varies with the bilayer
      thickness. The protein structures are kept constant and, at each membrane
      thickness, the protein is allowed to tilt and rotate in order to accommodate at
      their best. The conditions are said to be optimal when the energy of insertion is
      minimal. The results show that most helix bundles require thicker membranes than
      porin barrels. Moreover, in a few instances, the ideal membrane thickness is
      unrealistic with respect to natural membranes supporting that the X-ray structure
      requires adaptation to stabilize in membrane. For instance, the squalene cyclase
      could adapt by bending the side chains of its ring of lysine and arginine in
      order to increase the hydrophobic surface in contact with membranes. We analyzed
      the distribution of amino acids in the water, interface and acyl chain layers of
      the membrane and compared with the literature.

PMID- 12798388
TI  - Analysis and optimization of structure-based virtual screening protocols (1):
      exploration of ligand conformational sampling techniques.
AB  - Ligand conformational flexibility has long been recognized as an important issue
      in virtual screening (VS). To this end, a number of different methodologies have
      been adapted to tackle the problem. Many of said techniques were originally
      designed for ligand derived pharmacophore screens, but have subsequently been
      fashioned for application within structure-based virtual screening (SVS). A
      popular adaptation is the pre-calculation of diverse ligand conformations for
      subsequent docking in target active sites. In this paper, we study a number of
      the software programs currently being used in conformer generation, analyzing
      their ability to regenerate known ligand binding conformations. The implications
      of these studies are discussed, from the perspective of VS in general and SVS in
      particular.

PMID- 12798389
TI  - Analysis and optimization of structure-based virtual screening protocols. 2.
      Examination of docked ligand orientation sampling methodology: mapping a
      pharmacophore for success.
AB  - An important element of any structure-based virtual screening (SVS) technique is
      the method used to orient the ligands in the target active site. This has been a
      somewhat overlooked issue in recent SVS validation studies, with the assumption
      being made that the performance of an algorithm for a given set of orientation
      sampling settings will be representative for the general behavior of said
      technique. Here, we analyze five different SVS targets using a variety of
      sampling paradigms within the DOCK, GOLD and PROMETHEUS programs over a data set
      of approximately 10,000 noise compounds, combined with data sets containing
      multiple active compounds. These sets have been broken down by chemotype, with
      chemotype hit rate used to provide a measure of enrichment with a potentially
      improved relevance to real world SVS experiments. The variability in enrichment
      results produced by different sampling paradigms is illustrated, as is the
      utility of using pharmacophores to constrain sampling to regions that reflect
      known structural biology. The difference in results when comparing chemotype with
      compound hit rates is also highlighted.

PMID- 12798390
TI  - Analysis and optimization of structure-based virtual screening protocols. (3).
      New methods and old problems in scoring function design.
AB  - Scoring function research remains a primary focus of current structure-based
      virtual screening (SVS) technology development. Here, we present an alternative
      method for scoring function design that attempts to combine crystallographic
      structural information with data derived from directly within SVS calculations.
      The technique utilizes a genetic algorithm (GA) to optimize functions based on
      binding property data derived from multiple virtual screening calculations. These
      calculations are undertaken on protein data bank (PDB) complex active sites using
      ligands of known binding mode in conjunction with "noise" compounds. The
      advantages of such an approach are that the function does not rely on assay data
      and that it can potentially use the "noise" binding data to recognize the sub
      optimal docking interactions inherent in SVS calculations. Initial efforts in
      technique exploration using DOCK are presented, with comparisons made to existing
      DOCK scoring functions. An analysis of the problems inherent to scoring function
      development is also made, including issues in dataset creation and limitations in
      descriptor utility when viewed from the perspective of docking mode resolution.
      The future directions such studies might take are also discussed in detail.

PMID- 12798391
TI  - Modeling and molecular dynamics of glutamine transaminase K/cysteine conjugate
      beta-lyase.
AB  - The homodimeric, pyridoxal 5'-phosphate (PLP)-dependent enzyme glutamine
      transaminase K/cysteine conjugate beta-lyase (GTK/beta-lyase) has been implicated
      in the bioactivation of chemopreventive compounds. This paper describes the first
      homology model of rat renal GTK/beta-lyase and its active site residues, deduced
      from molecular dynamics (MD) simulations of the binding mode of 13 structurally
      diverse cysteine S-conjugates and amino acids after Amber-parametrization of PLP.
      Comparison with Thermus thermophilus aspartate aminotransferase (tAAT) and
      Trypanosoma cruzi tyrosine aminotransferase (tTAT), used as templates for
      modeling GTK/beta-lyase, showed that the PLP-binding site of GTK/beta-lyase is
      highly conserved. Binding of the ligand alpha-carboxylate-group occurred via the
      conserved residues Arg(432) and Asn(219), and Asn(50) and Gly(70). Two pockets
      accommodated the various ligand side chains. A small pocket, located directly
      above PLP, was of a highly hydrophobic and aromatic character. A larger pocket,
      formed partly by the substrate access channel, was more hydrophilic and notably
      involved the salt bridge partners Glu(54) and Arg(99*) (* denotes the other
      subunit). Ligand-binding residues included Leu(51), Phe(71), Tyr(135), Phe(373)
      and Phe(312*), and pi-stacking interactions were often observed. Tyr(135) and
      Asn(50) were prominent in hydrogen bonding with the sulfur-atom of cysteine S
      conjugates. The observed binding mode of the ligands corresponded well with their
      experimentally determined inhibitory potency toward GTK/beta-lyase. The current
      homology model thus provides a starting point for further validation of the role
      of active site residues in ligand-binding by means of mutagenesis studies.
      Ultimately, insight in the binding of ligands to GTK/beta-lyase may result in the
      rational design of new ligands and selective inhibitors.

PMID- 12798392
TI  - A web-based platform for virtual screening.
AB  - A fully integrated, web-based, virtual screening platform has been developed to
      allow rapid virtual screening of large numbers of compounds. ORACLE is used to
      store information at all stages of the process. The system includes a large
      database of historical compounds from high throughput screenings (HTS) chemical
      suppliers, ATLAS, containing over 3.1 million unique compounds with their
      associated physiochemical properties (ClogP, MW, etc.). The database can be
      screened using a web-based interface to produce compound subsets for virtual
      screening or virtual library (VL) enumeration. In order to carry out the latter
      task within ORACLE a reaction data cartridge has been developed. Virtual
      libraries can be enumerated rapidly using the web-based interface to the
      cartridge. The compound subsets can be seamlessly submitted for virtual screening
      experiments, and the results can be viewed via another web-based interface
      allowing ad hoc querying of the virtual screening data stored in ORACLE.

PMID- 12798393
TI  - Comparative pharmacophore development for inhibitors of human and rat 5-alpha
      reductase.
AB  - There are a number of diseases where the 5-alpha-reductase (5AR) enzyme is of
      therapeutic interest as a drug target. Currently the crystal structure for 5
      alpha-reductase is unavailable, thus ligand-based pharmacophore techniques are
      beneficial in the drug development process. We have developed pharmacophores to
      aid inhibitor design for both human types I (preliminary) and II 5-alpha
      reductase isozymes and also the rat type II isozyme. To our knowledge, these are
      the first published pharmacophores for inhibitors of the human type I and rat
      type II enzymes. A comparison between isozymes and the previously published human
      type II isozyme pharmacophore is also presented.

PMID- 12798394
TI  - 2,3,7,8-Tetrachloro dibenzo-p-dioxin can be successfully decomposed over 2:1
      dioctahedral smectite-a reactivity index study.
AB  - 2:1 Dioctahedral smectite family has shown its capability to decompose 2,3,7,8
      tetrachloro dibenzo-p-dioxin (TeCDD) using the active hydroxyl hydrogen attached
      with the central octahedral aluminum, as monitored using density functional
      theory (DFT). From the values of the local softness and the charge on the
      hydrogen atom of the bridging/structural (occurring on the surface) hydroxyl
      attached to octahedral/tetrahedral metal site present in smectite used as a first
      approximation to the local hardness, it is concluded that the local acidities of
      the inorganic material systems are dependent on several characteristics which are
      of importance within the framework of hard-soft acid-base (HSAB) principle. The
      first step in this process of decomposition is the abstraction of chlorine bound
      to TeCDD using surface hydrogen of smectites. This results in non-chlorinated
      dibenzo-p-dioxin (NCDD), which is less toxic than TeCDD. The second step is the
      formation of a dative bond between oxygen of NCDD and hydroxyl proton of
      smectite, with the breaking of Cz.sbnd;O bond of NCDD. The reaction mechanism is
      postulated within the helm of DFT using Fukui functions for all possible
      chlorinated and non-chlorinated dioxin varieties along with clay clusters. The
      material is identified to act for the decomposition of dioxin.

PMID- 12798395
TI  - Carcinogenesis and cyclooxygenase: the potential role of COX-2 inhibition in
      upper aerodigestive tract cancer.
AB  - Cyclooxygenase-2 (COX-2) is upregulated in a number of epithelial cancers,
      including in upper aerodigestive tract (UADT) premalignant and malignant lesions.
      The purpose of this review is to provide a comprehensive examination of the
      potential of COX-2 inhibition in prevention of UADT premalignant and malignant
      disease. A Medline and Cancerlit literature search was conducted for the period
      1993-2002, and identified literature was reviewed. There is evidence from in
      vitro studies, as well as animal models, that inhibition of COX-2 may suppress
      carcinogenesis by affecting a number of pathways of carcinogenesis, promoting
      apoptosis and inhibiting angiogenesis. Preliminary studies of gastro-intestinal
      (GI) carcinogenesis suggest that COX-2 inhibitors may represent an approach to
      the chemoprevention of epithelial cancers. COX-2 inhibitors may have a potential
      role in chemoprevention of UADT cancer, and clinical trials appear warranted.

PMID- 12798396
TI  - Impact of whole body positron emission tomography on initial staging and therapy
      in patients with squamous cell carcinoma of the oral cavity.
AB  - The aim of this study is to evaluate the additional clinical information provided
      by whole body positron emission tomography (PET) with fluorodeoxyglucose (FDG)
      for initial staging of patients with squamous cell carcinoma (SCC) of the oral
      cavity. PET scans from the head to the pelvic floor of 34 consecutive patients
      (22 male, 12 female; mean age 71 years) with histologically confirmed SCC of the
      oral cavity were retrospectively evaluated. Clinical information including CT of
      the head and neck and chest X-Ray or chest CT was compared with information on
      nodal involvement and distant metastases or secondary tumours obtained with PET.
      The primary tumour was identified with PET in 33 of 34 patients (97%). In 27
      Patients (81%) the clinical N-stage was confirmed with PET. In two Patients (6%)
      additional pathologic loco-regional lymph nodes were found. In five patients more
      lymph nodes were identified with CT. Distant lesions were seen with PET imaging
      in bone, lung, mediastinum, liver and colon. In three patients (6%) distant
      metastases were correctly identified. In another four patients (12%) a secondary
      cancer was detected. One false positive finding was described with PET. In five
      of 34 patients (15%) the additional findings as revealed with PET lead to a
      change of treatment. Whole body PET provides relevant additional information to a
      standard clinical staging procedure in patients with oral cavity SCC. The
      detection of distant metastases and secondary primary tumours can have a great
      impact on patient management.

PMID- 12798397
TI  - Larynx preservation surgery for advanced posterior pharyngeal wall carcinoma with
      free flap reconstruction: a critical appraisal.
AB  - To report the functional and oncologic results of larynx preservation surgery
      with free flap reconstruction for posterior pharyngeal wall carcinoma.
      Retrospective medical chart review. Tertiary care referral center. We present a
      series of seven patients, who were treated for an advanced stage posterior
      pharyngeal wall carcinoma between 1995 and 1998. All patients underwent posterior
      pharyngectomy with larynx preservation via a suprahyoidal approach for carcinoma
      of the posterior pharyngeal wall, with radial forearm free flap reconstruction.
      Complications occurred in three patients with grade 3 comorbidity, one of whom
      suffered flap loss. After a mean follow-up of 48 months, three patients are alive
      without disease. One patient is alive with a second primary tongue carcinoma. Two
      patients died of disease, whereas one patient died of another cause. All patients
      could be decannulated and maintain their voice. Six out of seven patients were
      able to take oral nutrition, although four patients needed additional PEG-tube
      feeding. Posterior pharyngectomy with larynx preservation and radial forearm free
      flap reconstruction is feasible in selected patients, with acceptable functional
      results and survival. However, the patient must be aware of the risk of chronic
      aspiration and the possibility of long-term PEG feedings.

PMID- 12798398
TI  - Upregulation of cystatin M during the progression of oropharyngeal squamous cell
      carcinoma from primary tumor to metastasis.
AB  - To identify metastasis-associated molecules in oropharyngeal squamous cell
      carcinomas (OSCC), we recently compared mRNA expression profiles of cell lines
      derived from primary and metastatic lesions of OSCC using microarray technology.
      Cystatin M, an endogenous cathepsin B inhibitor, was expressed 40-fold higher in
      the metastatic versus the primary tumor cell line. To show that different
      cystatin expression levels affect the cell lines' sensitivities to TNF-induced
      apoptosis by differentially regulating cathepsin B activity. The 686Tu and 686Ln
      cell lines were established from a 49-year-old male patient with an OSCC
      involving the posterior tongue and oro-pharynx (tumor stage T(3)N(3B)). RT-PCR,
      Western blots, immunohistochemistry, and in situ hybridization all confirmed
      increased cystatin M expression in 686Ln compared to 686Tu cells, and in the
      parent archival tumors. TNF-alpha induced apoptosis was easily detected in 686Tu,
      but only marginally in 686Ln cells. Thus, we propose that elevated cystatin M
      expression aids metastasis by blocking intrinsic cathepsin B activity and
      rescuing tumor cells from TNF-induced apoptosis.

PMID- 12798399
TI  - Decline of oropharyngeal cancer in Chiangmai province, Thailand, between 1988 and
      1999.
AB  - A decline of oropharyngeal cancer has already been predicted for Thailand since
      the early 1960s. To substantiate these predictions it was the purpose of this
      study to examine trends in the incidence of oropharyngeal cancer in the province
      of Chiangmai, (1988-1999). Data on cancer incidence were extracted from the
      annual reports of the Cancer Registry, Cancer Unit, Faculty of Medicine,
      Chiangmai University, Thailand (1992-1999) and an IARC report on cancer in
      Thailand (1988-1991). The age-standardized annual incidence per 100000 of oral
      cancer in males dropped from 3.6 (1988-1991) to 1.2 in 1999 (P for trend 0.0002)
      and in females from 2.6 (1988-1991) to 1.1 in 1999 (P for trend 0.007). Similar
      trends in males and females for cancer of the tongue, oropharynx and hypopharynx
      were seen. The age-standardized annual incidence for cancer of the lip, salivary
      gland and nasopharyngeal carcinoma remained unchanged. Changes of traditional
      oral habits such as betel quid chewing and smoking of traditional cigars seem to
      have resulted in a marked decrease of oral cancer in both men and women in the
      recent past.

PMID- 12798400
TI  - Assessment of pleomorphic adenomas using MRI and dynamic contrast enhanced MRI.
AB  - We evaluated magnetic resonance images (MRI) and the value of dynamic contrast
      enhanced MRI (DCE-MRI) of pleomorphic adenomas retrospectively. MRI was performed
      for 18 pleomorphic adenomas, including 11 cases with DCE-MRI. We obtained the
      following results on the MRI and DCE-MRI. (a). Pleomorphic adenomas showed a
      predilection for homogeneous intermediate signal intensity on T1-weighted images
      (T1WI), heterogeneous high signal intensity on T2-weighted images, and
      heterogeneous enhancement on Gd-T1WI. (b). Of 11 contrast index (CI) curves of
      pleomorphic adenomas, nine CI curves (81.8%) increased gradually to 600 s or
      increased gradually, reached a plateau, and sustained the plateau to 600 s. The
      remaining two (18.2%) increased gradually and decreased gradually thereafter.
      (c). CI curves reached the maximum CI index at 135-300 s.

PMID- 12798401
TI  - Interim results from a cluster randomized controlled oral cancer screening trial
      in Kerala, India.
AB  - A cluster randomized controlled oral cancer screening trial is on-going in the
      Trivandrum district, India, to evaluate the efficacy of screening in reducing
      oral cancer mortality. Subjects, aged 35 years and above, in 13 clusters in the
      Trivandrum district, India, were randomized to the intervention (screening) group
      (7 clusters, 78969 subjects) to receive three rounds of screening by oral visual
      inspection by trained health workers at 3-year intervals or to a control group (6
      clusters, 74739 subjects). Two rounds of screening were completed between 1995
      and 2002 during which 69896 (88.5%) subjects were screened at least once, and
      59.7% of the 4408 screen-positive subjects were further investigated. In the
      intervention group, 344404 person-years were accrued and 329326 person-years were
      in the control group. In the intervention group, 149 incident oral cancer cases
      and 65 deaths from oral cancer were observed, and 106 incident cases and 62
      deaths from oral cancer were observed in the control group. The programme
      sensitivity for detection of oral precancerous lesions and cancer was 81.5% and
      the programme specificity was 84.8%; the programme positive predictive value was
      39.6%. In the intervention group 37.6% of the cases were in stages I-II, as
      opposed to 18.9% in the control group. The 3 year survival rate was 57.5% in the
      intervention and 38.8% in the control group (P<0.05). The age standardized oral
      cancer mortality rates were 21.2/100000 person-years in the intervention and
      21.3/100000 in the control group. After completing two rounds of screening, oral
      cancer mortality rates were similar in both study groups.

PMID- 12798402
TI  - Oral epithelial dysplasia: clinical characteristics of western European
      residents.
AB  - To detail the clinical presentation of oral epithelial dysplasia in a large
      cohort of residents in western Europe. Descriptive statistical analysis of the
      data were calculated using chi-square and Fisher's exact tests. Oral epithelial
      dysplasia manifested typically as a white or mixed red and white lesion on the
      tongue, buccal mucosa or floor of mouth. The peak age of presentation of oral
      epithelial dysplasia was the 6th decade. Most clinically detected lesions had
      only mild oral epithelial dysplasia. Although uncommon, lesions with severe
      dysplasia were most likely to arise on the floor of mouth or lateral border of
      tongue. Oral epithelial dysplasia is likely to manifest as a solitary white
      patch, but it is not possible to accurately predict the likely degree of
      dysplasia from the clinical features of such lesions.

PMID- 12798403
TI  - A prospective evaluation of early thyroid dysfunction on completion of neck
      radiotherapy.
AB  - The purpose of this study was to examine thyroid dysfunction in the early phase
      of radiotherapy to the head and neck region. Forty-seven patients receiving neck
      irradiation including the thyroid gland were included. Twenty-eight patients had
      undergone either a functional or radical neck dissection and in 19 patients
      radiotherapy was the primary treatment. Compared to the pre-treatment values,
      there was a significant fall in the TSH level at completion of radiotherapy in
      the non-operated patients and a non-significant fall in the operated patients.
      The TSH was also significantly lower in the non-operated group at the end of
      treatment compared to the operated group. There was a significant fall in the FT3
      and significant higher in the FT4 at the end of radiotherapy for both groups.
      This study shows that even during completion of radiotherapy to the head and neck
      region changes in thyroid function were observed for both previously operated and
      non-operated patients.

PMID- 12798404
TI  - Improvement of transduction efficiency of recombinant adenovirus vector
      conjugated with cationic liposome for human oral squamous cell carcinoma cell
      lines.
AB  - Adenovirus (Ad) vectors are commonly used in gene therapy trials because of their
      efficiency in gene transfer. However, their use is limited by immune responses
      that reduce transgene expression and decrease the efficiency of repeated vector
      administration. In this study, the efficacy of gene transduction and the tumor
      cell killing effect on four human oral (SAS, HSC-2, HSC-3, HSC-4) and one murine
      squamous cell carcinoma cell (SCC-7, a kind gift of Dr. M. Hiraoka, Kyoto
      University) lines in vitro with Ad vector conjugated with catioic liposome
      (Ad/SUV) was evaluated. Ad/SUV resulted in two to five-fold over higher
      transduction efficiency in four human and one murine cell lines in vitro than Ad
      vector alone. The optimal Ad-SUV ratio was determined as 10(6) pfu of Ad vector
      with 1 micromol SUV. Ad/SUV showed more tumor-cell killing effect than Ad vector
      alone. Furthermore, the shielding effects of Ad vector with Ad/SUV from
      neutralizing antibody were evaluated. We also found that Ad/SUV is less
      susceptible to inactivation by neutralizing antibodies in vitro. The efficacy of
      gene transduction with Ad vector was blocked more than 70% with neutralizing
      serum, while Ad/SUV retained approximately 50% of the control activity in vitro.
      On the basis of these results, the anti-tumor effect with suicide gene therapy
      using Ad/SUV in vivo was evaluated. Three injections of Ad/SUV showed the
      inhibition of tumor growth compared with control in vivo. Our results suggested
      that an enhanced anti-tumor effect on human oral squamous cell carcinoma would be
      obtained with repeated administrations of Ad/SUV.

PMID- 12798405
TI  - Prognostic significance of cyclin D1 amplification and overexpression in oral
      squamous cell carcinomas.
AB  - Amplification and overexpression of cyclin D1 (CCND1) have been reported as
      independent prognostic indicators of several tumors. To investigate the
      association between CCND1 amplification and overexpression in oral squamous cell
      carcinomas (OSCCs), and to determine which is more reliable as a prognostic
      indicator, fluorescence in situ hybridization (FISH) on fine-needle aspiration
      (FNA) biopsies and immunohistochemistry were performed on 41 primary OSCCs (26
      males, 15 females; mean age; 58.4 years, range 21-89 years). Thirteen patients
      were stage I, 13 were stage II, nine were stage III, and six were stage IV. CCND1
      amplification and overexpression was detected in 13 (31.7%) and 27 (65.9%) of 41
      cases. CCND1 was overexpressed in all cases showing CCND1 amplification. On the
      other hand, CCND1 overexpression was also detected in 14 of 28 cases (50.0%)
      lacked such amplification. Statistical analysis showed that the correlation
      between CCND1 overexpression and decreased survival just failed to reach
      statistical significance, and CCND1 amplification and nodal status were
      independent prognostic indicators. In conclusion, it will be necessary to
      investigate the other pathways that regulate CCND1 expression besides CCND1
      amplification. From the present study, CCND1 amplification is a more reliable
      prognostic indicator than CCND1 overexpression in OSCCs.

PMID- 12798406
TI  - Low prevalence of oral leukoplakia in a representative sample of the US
      population.
AB  - Recent studies reported a tendency towards a lower prevalence of oral leukoplakia
      (OL), compared with the past. To assess the prevalence of OL in a representative
      sample of the US population, data from the oral mucosal tissue assessment and
      some other covariates of 16128 participants in the US National Health and
      Nutrition Examination Survey (NHANES III) were included. The clinical definition
      of OL was applied according to the WHO criteria. The weighted prevalence
      estimates of OL were 0.66+/-0.14% in males, 0.21+/-0.05% in females and 0.42+/
      0.08% in total. The age peaks were at 40-49 years in males and at >or=70 years in
      females. The prevalence estimates were 0.37% for homogeneous OL and 0.06% for non
      homogeneous OL. Gingiva (38.8%) and buccal mucosa (30.9%) were the most frequent
      locations. Compared to previous studies in the USA, a substantial decline of the
      prevalence of OL was shown.

PMID- 12798407
TI  - Solitary adult myofibroma of the mandible simulating an odontogenic cyst.
AB  - The solitary adult myofibroma is a rare lesion but has a predilection for the
      head and neck. Intraosseous lesions are common in childhood but uncommon in
      adults. The lesion is considered to be completely benign but there is the
      potential for it being confused with more aggressive spindle cell tumours.
      Histologically it is characterised by two cell types arranged in a biphasic
      pattern; namely centrally positioned small rounded cells with pale staining
      nuclei and eosinophilic cytoplasm and peripherally elongated spindle cells. A
      case is reported of a 34-year-old female patient who presented with a solitary
      myofibroma in the lower third molar region of the mandible which clinically and
      radiographically simulated an odontogenic cyst.

PMID- 12798408
TI  - Malignant transformation of oral lichen planus.

PMID- 12798410
TI  - The role of melanocortins and their receptors in inflammatory processes, nerve
      regeneration and nociception.
AB  - The melanocortins are a family of bioactive peptides derived from
      proopiomelanocortin. Those peptides, included among hormones and comprising ACTH,
      alpha-MSH, beta-MSH and gamma-MSH, are best known mainly for their physiological
      effects, such as the control of skin pigmentation by alpha-MSH, and ACTH effects
      on pigmentation and steroidogenesis. Melanocortins are released in various sites
      in the central nervous system and in peripheral tissues, and participate in the
      regulation of multiple physiological functions. They are involved in grooming
      behavior, food intake and thermoregulation processes, and can also modulate the
      response of the immune system in inflammatory states. Research of the past decade
      provided evidence that melanocortins could elicit their diverse biological
      effects by binding to a distinct family of G protein-coupled receptors with seven
      transmembrane domains. To date, five melanocortin receptor genes have been cloned
      and characterized. Those receptors differ in their tissue distribution and in
      their ability to recognize various melanocortins. These advances have opened up
      new horizons for exploring the significance of melanocortins, their ligands and
      their receptors for a variety of important physiological functions. We reviewed
      the origin of MSH peptides, the function and distribution of melanocortin
      receptors and their endogenous and exogenous ligands and the role of
      melanocortins and their receptors in inflammatory processes, nerve regeneration
      and nociception. Moreover, we analyzed their interaction with opioid peptides and
      finally, we discussed the postulated role of the melanocortin system in pain
      transmission at the spinal cord level.

PMID- 12798411
TI  - Disaccharide analysis of glycosaminoglycans synthesized by cardiac myxoma cells
      in tumor tissues and in cell culture.
AB  - We analyzed the main disaccharide units of glycosaminoglycans synthesized by
      cardiac myxoma cells in vivo and in cell culture using high-performance liquid
      chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling. Cardiac myxoma
      tissues contained large amounts of chondroitin-6-sulfate (46%) and hyaluronic
      acid (32%), along with some chondroitin-4-sulfate (13%), chondroitin (6%), and
      much less dermatan sulfate (3%). Cultured cardiac myxoma cells synthesized mainly
      chondroitin-6-sulfate. The abundant glycosaminoglycans in myxoma tissues may make
      up the characteristic friable gelatinous matrix which is favorable for embolism
      and tumor cell growth.

PMID- 12798413
TI  - Changes in the presence of progesterone receptor isoforms in the oviduct magnum
      of newly-hatched chicks after gonadotropins treatment.
AB  - The effects of Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) on
      progesterone receptor (PR) isoforms presence in different cell populations from
      the oviduct magnum of newly-hatched chicks treated in vivo on days 13, 15 and 17
      of embryonic development, were analyzed by immunohistochemistry. We found that
      FSH promoted cytodifferentiation of the magnum's mucosa and increased PR
      immunoreactivity in all cell types of the oviduct magnum, whereas LH-treatment
      did not exert cytodifferentiation of magnum's mucosa, and PR immunoreactivity was
      only induced in some epithelial and stromal cells of the oviduct magnum. In all
      treatments the number of PR immunopositive cells incubated with the antibody PgR
      Ab-8 that recognizes both PR isoforms were significantly higher than the number
      of immunopositive cells incubated with antibody PgR Ab-6 that only recognizes PR
      B. This suggests that PR-A should be the predominant isoform in the oviduct
      magnum of newly-hatched chicks treated with gonadotropins during embryonic
      development. We conclude that gonadotropins differentially regulate PR-A isoform
      presence in the oviduct magnum of newly-hatched chicks.

PMID- 12798412
TI  - Food effects on the absorption and pharmacokinetics of cocoa flavanols.
AB  - Macronutrients in food and gastric acid are known to have a pronounced effect on
      the metabolism of many xenobiotics, an effect that impacts their efficacy as
      bioactive agents. In this investigation we assessed the impact of select food
      treatments and the histamine H(2)-receptor antagonist Famotidine (Pepcid-AC) on
      flavanol absorption and metabolism. Four crossover intervention studies were
      conducted with 6 subjects each. Volunteers consumed sugar-free, flavanol-rich
      cocoa (0.125 g/kg body wt) alone, with macronutrient-rich foods (8.75 or 17.5
      kJ/kg subject body wt) or Famotidine (Pepcid-AC). Blood samples were drawn at 5
      time points including baseline. Plasma samples were analyzed for epicatechin and
      catechin flavanols by HPLC. Pharmacokinetic parameters were assessed using non
      compartmental methodology. When provided at 17.5 kJ/kg subject body weight
      (approximately 4 kcal/kg), sugar and bread test meals increased flavanol area
      under the curve (AUC) values to 140% of control values (P < 0.05). A
      corresponding tendency for plasma antioxidant capacity to increase was observed
      for the cocoa treatment at 1.5 and 2.5 h (P < 0.17, P < 0.06, respectively). The
      ability of treatment meals to affect AUC values was positively correlated with
      treatment carbohydrate content (r = 0.83; P< 0.02). In contrast to carbohydrate
      rich meals, lipid and protein rich meals and Famotidine treatment had minimal
      effects on flavanol absorption. Based on C(max) and AUC values, this data
      suggests that the uptake of flavanols can be increased significantly by
      concurrent carbohydrate consumption.

PMID- 12798415
TI  - Alpha-2 adrenoceptor mediating the facilitatory effect of norepinephrine on the
      glycine response in the spinal dorsal horn neuron of the rat.
AB  - Effects of norepinephrine (NE) on the glycine-mediated inhibitory response were
      investigated in neurons acutely dissociated from the rat spinal dorsal horn,
      using nystatin perforated patch recording mode under voltage-clamp conditions. NE
      reversibly and concentration dependently facilitated Cl(-) current induced by 3 x
      10(-5) M glycine. NE neither changed the reversal potential of the glycine
      response nor affected the affinity of glycine to its receptor. This effect could
      be mimicked by clonidine (10(-7) M) and blocked by yohimbine (10(-6) M),
      respectively. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride
      (H-89), an inhibitor of protein kinase A, effectively mimicked the effect of NE
      on glycine response, whereas chelerythrine (an inhibitor of protein kinase C)
      failed. NE further enhanced glycine response even in the presence of
      chelerythrine or stearoylcarnitine chloride (another inhibitor of protein kinase
      C) or chelerythrine together with stearoylcarnitine chloride. The present results
      suggest that alpha2-adrenoceptor is involved in the potentiation of NE on glycine
      response in freshly isolated spinal dorsal horn neurons. Activation of alpha2
      adrenoceptor down-regulates the activity of protein kinase A that results in the
      potentiation of the glycinergic inhibitory effects within the spinal dorsal horn.

PMID- 12798414
TI  - The effects of verbascoside on plasma lipid peroxidation level and erythrocyte
      membrane fluidity during immobilization in rabbits: a time course study.
AB  - We studied the changes in the level of plasma lipid peroxidation indicated by
      malondialdehyde (MDA) level and erythrocyte membrane fluidity expressed by the
      value of order parameter (S) during single hindlimb immobilization of 21 days
      using thiobarbituric acid - reactive substances method and spin label electron
      spin resonance method, respectively. The impacts of verbascoside that has been
      proved its antioxidative activity on the measured parameters were examined. 11
      New Zealand white rabbits were immobilized and divided into two groups. The
      rabbits in the verbascoside group were administrated with 0.8 mg/kg of
      verbascoside twice a day orally throughout the immobilization. The rabbits in the
      placebo group were treated with normal saline. In placebo group, the results
      showed that the level of MDA significantly increased on day 3, peaked on day 7,
      and was still significantly higher on day 14 of immobilization, compared with the
      value measured before immobilization. The value of S reached the highest on day 7
      and subsequently lowered but still higher on day 14 than those measured before
      immobilization. Compared with placebo group, there were lower MDA level (P <
      0.05, 0.001, and 0.05 for days 3, 7, and 14, respectively) and higher erythrocyte
      membrane fluidity (P < 0.05, 0.001, and 0.001 for days 3, 7, and 14,
      respectively) in verbascoside group. The data indicated that immobilization
      caused temporal changes of increase in plasma lipid peroxidation and decrease in
      erythrocyte membrane fluidity. Verbascoside might have the effects to moderate
      oxidative stress and erythrocyte membrane fluidity during immobilization.

PMID- 12798416
TI  - Increase in the number of integrinbeta1-immunoreactive monocyte-lineage cells in
      experimentally-induced adenomyosis in mice.
AB  - Uterine adenomyosis is a disease in which hyperplastic endometrial stroma and
      glands invade the myometrium. We have previously demonstrated that
      hyperprolactinemia leads to the development of adenomyosis in mice. In the
      present study, a subtracted cDNA library was made by suppression subtractive
      hybridization to find specific genes that are abundantly expressed in the
      adenomyotic but not normal tissue in mice. A cDNA fragment of integrinbeta1
      (ibeta1) was found in the library, and the expression of the gene product was
      increased in the adenomyotic uteri at mRNA and protein levels. Intense ibeta1
      immunoreactivity was localized on a group of cells dispersing throughout the
      endometrial stroma. The number of ibeta1-immunoreactive (ibeta1-ir) cells was
      significantly greater in the uteri of mice with adenomyosis than normal mice. The
      majority of the ibeta1-ir cells expressed CD14-ir signal, a marker for monocyte
      lineage cells, whereas an increase in the number of CD14-ir cells was also
      evident in the adenomyotic uteri, especially in the ectopic endometrial tissue.
      Thus, the adenomyotic stromal tissue contained numerous monocyte-lineage cells
      with higher expression levels of ibeta1, one of their products. The relationship
      between the increased number of monocyte-lineage cells and the hyperplastic
      proliferation of endometrial tissues was discussed with a view to understanding
      the progressive mechanism of adenomyosis.

PMID- 12798417
TI  - Characterization of a novel C. elegans RGS protein with a C2 domain: evidence for
      direct association between C2 domain and Galphaq subunit.
AB  - RGS (regulator of G protein signaling) proteins are GTPase-activating proteins
      (GAPs) for heterotrimeric G protein alpha subunits and negatively regulate G
      protein-mediated signal transduction. In this study, we determined the cDNA
      sequence of a novel Caenorhabditis elegans (C. elegans) RGS protein. The
      predicted protein, termed C2-RGS, consists of 782 amino acids, and contains a C2
      domain and an RGS domain. C2 domains are typically known to be Ca(2+) and
      phospholipid binding sites, found in many proteins involved in membrane traffic
      or signal transduction, and most of their biological roles are not identified. To
      study the function of C2-RGS protein, a series of six truncated versions of C2
      RGS were constructed. When the full-length protein of C2-RGS was expressed
      transiently in AT1a-293T cells, ET-1-induced Ca(2+) responses were strongly
      suppressed. When each of the mutants with either RGS domain or C2 domain was
      expressed, the Ca(2+) responses were suppressed moderately. Furthermore, we found
      that C2 domain of PLC-beta1 also had a similar moderate inhibitory effect. RGS
      domain of C2-RGS bound to mammalian and C. elegans Galphai/o and Galphaq subunits
      only in the presence of GDP/AlF(4)(-), and had GAP activity to Galphai3. On the
      other hand, C2 domains of C2-RGS and PLC-beta1 also bound strongly to Galphaq
      subunit, in the presence of GDP, GDP/AlF(4)(-), and GTPgammaS, suggesting the
      stable persistent association between these C2 domains and Galphaq subunit at any
      stage during GTPase cycle. These results indicate that both the RGS domain and
      the C2 domain are responsible for the inhibitory effect of the full-length C2-RGS
      protein on Galphaq-mediated signaling, and suggest that C2 domains of C2-RGS and
      PLC-beta1 may act as a scaffold module to organize Galphaq and the respective
      whole protein molecule in a stable signaling complex, both in the absence and
      presence of stimulus.

PMID- 12798418
TI  - Role of naringin supplement in regulation of lipid and ethanol metabolism in
      rats.
AB  - The current study was performed to investigate the effect of naringin supplements
      on the alcohol, lipid, and antioxidant metabolism in ethanol-treated rats. Male
      Sprague-Dawley rats were randomly divided into six groups (n = 10) based on six
      dietary categories: ethanol and naringin-free, ethanol (50 g/L) plus low-naringin
      (0.05 g/L), ethanol plus high-naringin (0.125 g/L), and three corresponding pair
      fed groups. The pair-fed control rats received an isocaloric diet containing
      dextrin-maltose instead of ethanol for 5 wks. Among the ethanol treated groups,
      the naringin supplements significantly lowered the plasma ethanol concentration
      with a simultaneous increase in the ADH and/or ALDH activities. However, among
      the ethanol-treated groups, naringin supplementation resulted in a significant
      decrease in the hepatic triglycerides and plasma and hepatic total cholesterol
      compared to that in the naringin-free group. Naringin supplementation
      significantly increased the HDL-cholesterol and HDL-C/total-C ratio, while
      lowering the AI value among the ethanol-treated groups. Hepatic lipid
      accumulation was also significantly reduced in the naringin-supplemented groups
      compared to the naringin-free group among the ethanol-treated groups, while no
      differences were found among the pair-fed groups. Among the ethanol-treated
      groups, the low-naringin supplementation resulted in a significant decrease in
      the levels of plasma and hepatic TBARS, whereas it resulted in higher SOD and GSH
      Px activities and gluthathion levels in the liver. Accordingly, naringin would
      appear to contribute to alleviating the adverse effect of ethanol ingestion by
      enhancing the ethanol and lipid metabolism as well as the hepatic antioxidant
      defense system.

PMID- 12798419
TI  - Activation of peripheral delta opioid receptors eliminates cardiac electrical
      instability in a rat model of post-infarction cardiosclerosis via mitochondrial
      ATP-dependent K+ channels.
AB  - The effects of the selective delta-1 (delta(1)) opioid receptor agonist, DPDPE,
      and the selective delta(2) opioid receptor agonist, DSLET, have been studied on
      the ventricular fibrillation threshold (VFT) in rats with an experimental post
      infarction cardiosclerosis (CS). It has been found that CS induced a significant
      decrease in VFT. This CS-induced decrease in VFT was significantly reversed by
      intravenous administration of DPDPE (0.1 mg/kg) 10 min before VFT measurement. On
      the contrary, intravenous injection of DSLET (0.5 mg/kg) exacerbated the CS
      induced cardiac electrical instability. Pretreatment with the selective delta
      opioid receptor antagonist, ICI 174,864 (0.5 mg/kg), completely abolished the
      changes in VFT produced by both DPDPE and DSLET. Previous administration of a
      nonselective peripherally acting opioid receptor antagonist, naloxone methiodide
      (5 mg/kg) also completely reversed the antifibrillatory action of DPDPE. Naloxone
      methiodide and ICI 174,864 alone had no effect on VFT. Pretreatment with the
      nonselective K(ATP) channel blocker, glibenclamide (0.3 mg/kg), or with the
      mitochondrial selective K(ATP) channel blocker, 5-hydroxydecanoic acid (5-HD, 5
      mg/kg), completely abolished the DPDPE-induced increase in cardiac electrical
      stability. Glibenclamide and 5-HD alone had no effect on VFT. These results
      demonstrate that the delta opioid receptor plays an important role in the
      regulation of electrical stability in rats with post-infarction cardiosclerosis.
      We propose that peripheral delta(1) opioid receptor stimulation reverses CS
      induced electrical instability via mitochondrial K(ATP) channels. On the
      contrary, delta(2) opioid receptor stimulation may exacerbate the CS-induced
      decrease in VFT. Further studies are necessary to determine the delta opioid
      receptor subtype which mediates the antifibrillatory effect of DPDPE and pro
      fibrillatory effect of DSLET.

PMID- 12798420
TI  - Structural correlates of electrical remodeling in ventricular hypertrophy.

PMID- 12798421
TI  - Pharmacological electrical remodelling in human atria induced by chronic beta
      blockade.

PMID- 12798422
TI  - New strategies in the surgical treatment of atrial fibrillation.
AB  - In patients with longstanding atrial fibrillation surgical correction of the
      underlying cardiac abnormality alone will not abolish the arrhythmia. The Cox's
      Maze III has proven to be an effective treatment for atrial fibrillation but
      because of its complexity cardiac surgeons are reluctant to expose their patients
      to the potential risks of this procedure. Attempts have been made to simplify the
      Cox's Maze III procedure by using alternative energy sources and modifying the
      pattern of atrial lines of conduction block. In patients with atrial fibrillation
      without structural heart disease Maze surgery may be an option as an ultimate
      therapeutic alternative when atrial fibrillation is drug resistant and very
      symptomatic. The objective of this article is to outline the different surgical
      procedures that have formerly been used in the treatment of atrial fibrillation
      and to give an overview of new and evolving techniques.

PMID- 12798423
TI  - Absence of reverse electrical remodeling during regression of volume overload
      hypertrophy in canine ventricles.
AB  - OBJECTIVE: Ventricular hypertrophy predisposes for cardiac arrhythmias,
      presumably due to prolongation of repolarization (electrical remodeling). The
      temporal relation between the development of hypertrophy and electrical
      remodeling, as well as their reversibility upon restoration of normal load,
      however, are poorly understood. This was investigated in the present study using
      volume overload hypertrophy induced by atrio-ventricular (AV) block and
      normalization of load by pacing. METHODS: Dogs were subjected to either 16 weeks
      of AV-block (CAVB group, n=9) or 8 weeks of AV-block followed by 8 weeks of right
      ventricular (RV) pacing at physiological heart rate (CAVB+PACE group, n=9).
      RESULTS: Left ventricular (LV) mass (2D-echocardiography) increased after 8 weeks
      of AV-block to approximately 30% above baseline and returned to 10+/-14% after 8
      weeks of pacing. QT-time (surface ECG) also increased after AV-block. However, 8
      weeks of pacing did not decrease QT and QTc-time (c=corrected for heart rate),
      neither during physiological pacing nor during temporary pacing at 100 beats/min.
      Lack of reverse electrical remodeling was confirmed by the absence of changes in
      LV and RV action potential duration (monophasic action potentials) at week 8 and
      16. CONCLUSIONS: In volume overload hypertrophy due to AV-block, structural and
      electrical remodeling develop in parallel but restoration of physiological heart
      rate causes dissociation between reverse structural remodeling and reverse
      electrical remodeling.

PMID- 12798424
TI  - Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology:
      evidence of pharmacological remodelling.
AB  - OBJECTIVE: Chronic beta-adrenoceptor antagonist (beta-blocker) treatment reduces
      the incidence of reversion to AF in patients, possibly via an adaptive myocardial
      response. However, the underlying electrophysiological mechanisms are presently
      unclear. We aimed to investigate electrophysiological changes in human atrial
      cells associated with chronic treatment with beta-blockers and other
      cardiovascular-acting drugs. METHODS: Myocytes were isolated enzymatically from
      the right atrial appendage of 40 consenting patients who were in sinus rhythm.
      The cellular action potential duration (APD), effective refractory period (ERP),
      L-type Ca(2+) current (I(CaL)), transient (I(TO)) and sustained (I(KSUS)) outward
      K(+) currents, and input resistance (R(i)) were recorded using the whole cell
      patch clamp. Drug treatments and clinical characteristics were compared with
      electrophysiological measurements using simple and multiple regression analyses.
      P<0.05 was taken as statistically significant. RESULTS: In atrial cells from
      patients treated chronically with beta-blockers, the APD(90) and ERP (75
      beats/min stimulation) were significantly longer, at 213+/-11 and 233+/-11 ms,
      respectively (n=15 patients), than in cells from non-beta-blocked patients, at
      176+/-12 and 184+/-12 ms (n=11). These cells also displayed a significantly
      reduced action potential phase 1 velocity (22+/-3 vs. 34+/-3 V/s). Chronic beta
      blockade was also associated with a significant reduction in the heart rate (58+/
      3 vs. 69+/-5 beats/min) and in the density of I(TO) (8.7+/-1.3 vs. 13.7+/-2.1
      pA/pF), an increase in the R(i) (214+/-24 vs. 132+/-14 MOmega), but no
      significant change in I(CaL) or I(KSUS). The I(TO) blocker 4-aminopyridine
      largely mimicked the changes in phase 1 and ERP associated with chronic beta
      blockade, in cells from non-beta-blocked patients. Chronic treatment of patients
      with calcium channel blockers or angiotensin converting enzyme inhibitors (n=11
      13 patients) was not associated with any significant changes in atrial cell
      electrophysiology. CONCLUSION: The observed atrial cellular electrophysiological
      changes associated with chronic beta-blockade are consistent with a long-term
      adaptive response, a type of 'pharmacological remodelling', and provide
      mechanistic evidence supportive of the anti-arrhythmic actions of beta-blockade.

PMID- 12798425
TI  - Calcium and potassium currents in cells from adult and aged canine right atria.
AB  - BACKGROUND: Action potential (AP) contours vary considerably between normal adult
      and aged right atrial fibers. The ionic bases for these differences remain
      unknown. Therefore we studied Ca(2+) and K(+) currents in cells from adult and
      aged canine right atria (RA). METHODS AND RESULTS: We used whole cell patch clamp
      recording techniques to measure L-type Ca(2+) currents (I(CaL)) with either
      Ca(2+) or Ba(2+) (3 mM) as the charge carrier, and both the transient outward
      (I(to)) and sustained potassium currents (I(sus)) in cells dispersed from normal
      adult (Adult, 2-5 years) and older dogs (Aged, >8 years). There is a significant
      reduction in peak I(CaL) (47%) and I(BaL) (43%) in Aged cells, yet differences in
      I(BaL) disappear with maximal beta adrenergic stimulation (isoproterenol, 1
      microM). Composite I(to) and I(sus) densities were significantly increased in the
      Aged versus Adult cell group (by 31 and 27% at +50 mV, respectively). I(to) decay
      during a maintained depolarization was slowed in Aged cells. Furthermore, I(to)
      steady-state inactivation curve was shifted positively in Aged cells. Finally,
      composite I(to) and I(sus) currents of Aged cells were more sensitive to
      tetraethylammonium chloride (TEA), a specific inhibitor of some types of K(+)
      currents. In the presence of TEA (5 mM), I(to) in Aged cells was significantly
      greater than that in Adult cells. CONCLUSIONS: Ionic currents differ in Aged
      versus Adult right atrial cells, such that a reduced Ca(2+) current and augmented
      outward currents could contribute significantly to the altered AP contour of the
      Aged RA cell. Adrenergic stimulation appears to restore Ba(2+) currents in Aged
      cells. Finally, an augmented TEA sensitive current plays a role in changes of
      I(sus) in Aged right atrial cells.

PMID- 12798426
TI  - Fetal and postnatal development of Ca2+ transients and Ca2+ sparks in rat
      cardiomyocytes.
AB  - OBJECTIVE: The aim of this study was to characterize the spatio-temporal dynamics
      of [Ca(2+)](i) in rat heart in the fetal and neonatal periods. METHODS: Using
      confocal scanning laser microscopy and the Ca(2+) indicator fluo-3, we
      investigated Ca(2+) transients and Ca(2+) sparks in single ventricular myocytes
      freshly isolated from rat fetuses and neonates. T-tubules were labeled with a
      membrane-selective dye (di-8-ANEPPS). Spatial association of dihydropyridine
      receptors (DHPR) and ryanodine receptors (RyR) was also examined by double
      labeling immunofluorescence. RESULTS: Ca(2+) transients in the fetal myocytes
      were characterized by slower upstroke and decay of [Ca(2+)](i) compared to those
      in adult myocytes. The magnitude of fetal Ca(2+) transients was decreased after
      application of ryanodine (1 microM) or thapsigargin (1 microM). However, Ca(2+)
      sparks were rarely detected in the fetal myocytes. Frequent ignition of Ca(2+)
      sparks was established in the 6-9-day neonatal period, and was predominantly
      observed in the subsarcolemmal region. The developmental change in Ca(2+) sparks
      coincided with development of the t-tubule network. The immunofluorescence study
      revealed colocalization of DHPR and RyR in the postnatal period, which was,
      however, not observed in the fetal period. In the adult myocytes, Ca(2+) sparks
      disappeared after disruption of t-tubules by glycerol incubation (840 mM).
      CONCLUSIONS: The sarcoplasmic reticulum (SR) of rat ventricular myocytes already
      functions early in the fetal period. However, ignition of Ca(2+) sparks depends
      on postnatal t-tubule formation and resultant colocalization of DHPR and RyR.

PMID- 12798427
TI  - Sex differences in the rate dependence of the T wave descending limb.
AB  - OBJECTIVE: The interval from the peak to the end of the T wave (TpTe) has been
      proposed to reflect the heterogeneity of action potential durations within the
      ventricular wall. Several studies have previously described TpTe to be
      independent of heart rate, which contradicts the in vitro observation of marked
      changes in transmural repolarisation heterogeneity due to cycle length changes.
      Because of this inconsistency, we investigated heart rate related changes of TpTe
      interval. METHODS: During 24-h recordings (SEER MC, Marquette GE) in healthy
      young women (n=25, 26+/-7 years) and men (n=25, 27+/-8 years), a 10-s 12-lead ECG
      was obtained every 30 s. Recordings were repeated after 1 day, 1 week, and 1
      month and results in each subject were pooled together and grouped for women and
      men. The QT and QT(peak) intervals were obtained automatically using QT Guard
      software (Marquette) and TpTe was computed as the difference between QT and
      QT(peak). In each subject TpTe values were averaged over 10-ms RR interval bands
      from 550 to 1150 ms. RESULTS: In both sexes, TpTe interval showed marked rate
      dependence with prolongation at long RR intervals. TpTe intervals in men were
      significantly longer over the entire range of investigated RR intervals
      (P=1.4x10(-25)). However, whereas the difference between sexes was marked at
      short cycle length (RR interval bin 540-550 ms: women 87+/-5 vs. men 95+/-9,
      P=5.1x10(-4)) it decreased at long cycle lengths (RR interval bin 1140-1150 ms:
      women 99+/-5 vs. men 106+/-6, P=9.3x10(-4)). CONCLUSION: There is a marked rate
      dependence of TpTe interval, which differs between women and men. The finding is
      consistent with the TpTe interval being an approximate surrogate of the
      intraventricular repolarisation gradient. The rate dependent increase in
      transmural repolarisation heterogeneity might be one of the reasons for the
      increased propensity of torsades de pointes in women.

PMID- 12798428
TI  - Aldosterone receptor blockade improves left ventricular remodeling and increases
      ventricular fibrillation threshold in experimental heart failure.
AB  - OBJECTIVES: To investigate the effects of aldosterone receptor blockade in
      postinfarction heart failure. METHODS: Eighty-seven rats with moderate myocardial
      infarction were randomized to receive either no drug or canrenone, the active
      metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a
      combination of the two drugs. Treatment was initiated 1 month after coronary
      ligation and lasted 4 weeks. Echocardiography was performed at baseline and after
      4 weeks. LV catheterization, isolated heart studies, morphometric histology,
      myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the
      treatment period. RESULTS: Infarct sizes were 33+/-3, 32+/-3, 34+/-3, and 34+/-4%
      in the placebo, canrenone, ramipril, and combination groups, respectively.
      Canrenone attenuated LV remodeling, improved LV systolic and diastolic function,
      and markedly reduced interstitial and perivascular fibrosis. These effects were
      increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine
      content was decreased while ventricular fibrillation threshold significantly
      augmented by canrenone. SERCA-2 levels remained unchanged. CONCLUSIONS: Canrenone
      attenuated LV dilation and interstitial remodeling, and improved LV filling
      dynamics and systolic function in the rat model of postinfarction heart failure.
      Addition of ramipril conferred further cardioprotection. Canrenone also reduced
      myocardial norepinephrine content and increased ventricular fibrillation
      threshold. The data provide a potential explanation for the decreased sudden
      death observed in the RALES study. The mechanisms of action of aldosterone
      inhibition are still poorly understood, despite its proven efficacy in heart
      failure. Rats with postinfarction heart failure were randomized to receive for 1
      month either no drug or canrenone, or ramipril, or a combination of canrenone and
      ramipril. Canrenone treatment was associated with a significant attenuation of LV
      dilation, better LV diastolic and systolic dynamics, and a marked reduction of
      reactive fibrosis. These effects were enhanced by concomitant ramipril therapy.
      Moreover, canrenone increased ventricular fibrillation threshold and reduced
      myocardial norepinephrine content. The data may explain the reduced mortality
      demonstrated by the RALES.

PMID- 12798430
TI  - Effect of exercise training on the ability of the rat heart to tolerate hydrogen
      peroxide.
AB  - OBJECTIVE: The purpose of this study was to determine whether exercise training
      could precondition the myocardium against hydrogen peroxide (H(2)O(2))-induced
      damage. METHODS: Male Fischer 344 rats ran on a treadmill for 9 weeks (60
      min/day, 22 m/min, 6 degrees grade, 5 days/week). Isolated perfused working
      hearts from exercise trained (ET, n=8) and sedentary (SED, n=10) animals were
      perfused with 150 microM H(2)O(2). RESULTS: Pre-H(2)O(2) baseline values for
      cardiac external work (COxSP), coronary flow (CF), and lactate dehydrogenase
      (LDH) release were similar between groups. At 5 min of H(2)O(2), COxSP was
      unchanged from baseline but CF was increased 30% in SED and 46% in ET (P<0.05 vs.
      SED). COxSP began to decline similarly thereafter in both groups, dropping to 20%
      of baseline at 20 min. CF in ET remained higher than SED throughout (P<0.05). LDH
      leakage remained near baseline during the first 15 min of H(2)O(2) exposure, but
      was elevated (P<0.05) 72% in SED and 40% in ET after 20 min, and was 2.2-fold
      greater in SED than ET (P<0.05) after 25 min. Heat shock protein 70 was 2.1-fold
      greater in ET than SED (P<0.05), but ET did not change catalase and glutathione
      peroxidase. CONCLUSIONS: The results of this study indicate that chronic moderate
      exercise will enhance coronary flow and attenuate the development of myocardial
      injury when exposed to H(2)O(2), but will not affect H(2)O(2)-induced decrease in
      pump function.

PMID- 12798429
TI  - Impact of alpha-tocopherol on cardiac hypertrophy due to energy metabolism
      disorder: the involvement of 1,2-diacylglycerol.
AB  - OBJECTIVE: The juvenile visceral steatosis (JVS) mouse, a murine model of
      systemic carnitine deficiency, shows a disorder of fatty acid oxidation and
      develops cardiac hypertrophy associated with lipid accumulation. Recently, alpha
      tocopherol was shown to decrease 1,2-diacylglycerol (DAG) levels. We investigated
      the involvement of DAG in cardiac hypertrophy due to energy metabolism disorder
      by evaluating the effects of alpha-tocopherol administration on the hearts of JVS
      mice. METHODS: Both JVS and control mice were fed a high alpha-tocopherol diet or
      a standard diet from 4 to 8 weeks of age. Myocardial DAG levels and fatty acid
      composition were assessed at 8 weeks of age. RESULTS: The ventricular to body
      weight ratio in the JVS mice was significantly higher than that in the control
      mice [11.2+/-0.1 (mean+/-S.E.M.) versus 3.8+/-0.1 mg/g, P<0.01], and was reduced
      by alpha-tocopherol treatment (9.7+/-0.2 mg/g, P<0.01 versus JVS mice). However,
      echocardiographic analysis showed the exaggeration of left ventricular dilatation
      in the alpha-tocopherol treated JVS mice (P<0.01 versus JVS mice). The myocardial
      thiobarbituric-acid-reactive substance level was not affected by alpha-tocopherol
      treatment. The myocardial DAG level was 2.5-fold higher in the JVS mice compared
      with that in the control mice (2004+/-136 versus 806+/-36 ng/mg dry weight,
      P<0.01) with a significant increase in 18:1 and 18:2 fatty acids. alpha
      Tocopherol treatment reduced myocardial DAG levels in the JVS mice (1443+/-49
      ng/mg dry weight, P<0.01 versus JVS mice) without any alteration of the fatty
      acid composition. CONCLUSIONS: alpha-Tocopherol treatment may partially reduce
      cardiac hypertrophy but it may also depress cardiac function in the JVS mice by
      decreasing the myocardial DAG level. An increase in DAG might be involved in the
      development of cardiac hypertrophy and in the maintenance of cardiac function in
      energy metabolism disorder of the heart.

PMID- 12798431
TI  - COX-2: an in vivo evidence of its participation in heat stress-induced myocardial
      preconditioning.
AB  - OBJECTIVE: Heat stress (HS) is known to induce delayed protection against
      myocardial infarction. We have previously shown that inducible nitric oxide
      synthase (iNOS), was involved in mediating this form of preconditioning. Since
      iNOS and cyclooxygenase-2 (COX-2) are co-induced in various cell types, the goal
      of this study was to investigate whether COX-2 could also participate to the HS
      induced cardioprotection. METHODS AND RESULTS: A total of 78 male Wistar rats,
      subjected to either heat stress (42 degrees C for 15 min) or sham anaesthesia
      were used for this study. Twenty-four hours later, they were treated or not with
      a selective COX-2 inhibitor, either celecoxib (3 mg kg(-1), i.p.) or NS-398 (5 mg
      kg(-1), i.p.), 30 min before being subjected to a 30-min occlusion of the left
      coronary artery followed by a 120-min reperfusion, in vivo. HS resulted in a
      marked increase in myocardial COX-2 protein expression at 24 h, associated with a
      significant protection against infarction (46.0+/-1.4% in sham vs. 26.8+/-3.8% in
      HS group) (P<or=0.05). Administration of selective COX-2 inhibitor 24 h after HS,
      completely abrogated this delayed cardioprotection (46.4+/-3.6 and 48.0+/-2.8%,
      respectively, in HS+celecoxib and HS+NS-398 groups). CONCLUSION: This study
      provides the first evidence of an implication of COX-2 as a mediator of HS
      induced cardioprotection. This suggests that prostaglandins are involved in this
      type of cardioprotective preconditioning.

PMID- 12798433
TI  - Trapidil protects ischemic hearts from reperfusion injury by stimulating PKAII
      activity.
AB  - OBJECTIVE: The cardioprotective effects of trapidil on ischemic reperfused (I/R)
      rabbit hearts were studied. Recently, we had shown that trapidil might activate
      protein kinase A (PKA). In this study, we examined the exact mode of PKA
      stimulating activity of trapidil. Finally, we investigated the effect of trapidil
      on the phosphorylation state of phospholamban (PLB), a major PKA target in the
      heart and key regulator of Ca(2+) sequestration via the sarcoplasmic reticulum
      Ca(2+)-ATPase. METHODS: Langendorff-hearts of New Zealand White rabbits were
      perfused at constant volume and subjected to global low-flow ischemia for 2 h,
      followed by 1 h of reperfusion. Subsequently, hearts were used for Western blot
      analysis of PLB phosphorylation. Furthermore, three different regulatory subunits
      and one catalytic subunit of PKA were overexpressed in E. coli. These PKA
      subunits were purified and used in an in vitro assay system to test the impact of
      trapidil on PKA activities in the absence and presence of cAMP. RESULTS: I/R
      resulted in a significant increase in left ventricular end-diastolic pressure and
      creatine kinase efflux in the hearts. Trapidil (10 microM) prevented these
      alterations. Using recombinant cAMP-free PKA isoforms, it was found that trapidil
      specifically stimulated PKAII but only did so in the presence of small amounts of
      added cAMP. Furthermore, the PKA-dependent 16Ser phosphorylation of PLB was
      markedly reduced in I/R. Trapidil largely normalized the 16Ser phosphorylation of
      PLB. CONCLUSIONS: The data demonstrate cardioprotective actions of trapidil in
      I/R and show a PKAII-dependent cAMP sensitizing effect of the compound. They also
      indicate PKA-dependent PLB phosphorylation as a target, suggesting an improved
      Ca(2+) uptake by the sarcoplasmic reticulum. This action might be involved in the
      cardioprotective effects of trapidil.

PMID- 12798432
TI  - Adenosine-mediated early preconditioning in mouse: protective signaling and
      concentration dependent effects.
AB  - OBJECTIVES: Signaling in adenosine-mediated preconditioning is controversial. We
      examined roles of mitochondrial (mito) K(ATP) channels, protein kinase C (PKC)
      and nitric oxide (NO). METHODS: Langendorff perfused C57/Bl6 mouse hearts were
      subjected to 20 min ischemia and 45 min reperfusion. Effects of adenosine
      mediated preconditioning were assessed in the absence and presence of signaling
      inhibitors. RESULTS: Control hearts recovered 70+/-2 mmHg ventricular pressure,
      and released 18.1+/-2.0 IU/g lactate dehydrogenase (LDH). Preconditioning with 10
      microM adenosine limited necrosis (10.6+/-1.4 IU/g) without modifying
      contractility (72+/-2 mmHg) whereas 50 microM adenosine reduced necrosis (10.3+/
      1.6 IU/g) and contractile dysfunction (91+/-2 mmHg). All protective effects of 10
      and 50 microM adenosine were abrogated by mito K(ATP) channel blockade with 100
      microM 5-hydroxydecanoate (5-HD) during the 'trigger' phase, but unaltered by PKC
      or NO synthase inhibition with 3 microM chelerythrine or 100 microM N(G)-nitro-L
      arginine methyl ester (L-NAME), respectively. Protection against necrosis was
      eliminated by 5-HD but unaltered by chelerythrine or L-NAME during the
      'mediation' phase (ischemia-reperfusion). Reduced contractile dysfunction with 50
      microM adenosine was partially sensitive to 5-HD and chelerythrine, and only
      eliminated by co-infusion of the inhibitors. CONCLUSIONS: Adenosine-mediated
      preconditioning is dose-dependent with high level stimulation reducing
      contractile dysfunction in addition to necrosis. Preconditioning is triggered by
      a mito K(ATP) channel dependent process independently of PKC and NO. Subsequent
      protection against necrosis is also mediated by a mito K(ATP) channel dependent
      process independent of PKC and NO. In contrast, functional protection may be
      mediated by parallel mito K(ATP) and PKC dependent paths.

PMID- 12798435
TI  - Lung structural remodeling and pulmonary hypertension after myocardial
      infarction: complete reversal with irbesartan.
AB  - OBJECTIVES: The severity of pulmonary hypertension associated with heart failure
      carries a poor prognosis. The lungs are very sensitive to the constrictive and
      proliferative effects of angiotensin-II and could represent a preferential target
      for this peptide. METHODS: Rats with large myocardial infarcts or sham surgery
      received the angiotensin-II receptor antagonist irbesartan (40 mg/kg/day) or
      vehicle for 2 or 8 weeks (n=5 to 8 for each group). Hemodynamic and morphometric
      measurements were obtained followed by immunohistochemistry, immunofluorescence
      analysis and electron microscopic characterization of lung sections. RESULTS: The
      infarct groups developed progressive pulmonary hypertension and right ventricular
      hypertrophy with elevated left ventricular filling pressures (all P<0.01).
      Despite similar infarct size, filling pressures were lower (P<0.01) while
      pulmonary hypertension and right ventricular hypertrophy were completely
      normalized by irbesartan. Isolated lungs pressure-flow relationships were
      identical at 2 weeks. At 8 weeks it was steepest and shifted upward in the
      infarct group (P<0.001), and completely normalized by irbesartan. Lung weight
      doubled after infarct with no evidence of pulmonary edema and was also normalized
      by irbesartan. Important lungs structural remodeling evidenced by collagen and
      reticulin deposition, thickening of the alveolar septa and proliferation of cells
      with ultrastructural characteristics of myofibroblasts (pericytes) were
      identified after infarct. CONCLUSIONS: After large myocardial infarct there is
      important pulmonary structural remodeling in which myofibroblasts (pericytes)
      proliferation may play an important role. This initially protective mechanism
      against high filling pressures could eventually contribute to the development of
      pulmonary hypertension and right ventricular hypertrophy. Future studies are
      needed to determine if angiotensin-II directly modulates pulmonary remodeling
      after myocardial infarct.

PMID- 12798434
TI  - Should increasing the dose or adding an AT1 receptor blocker follow a relatively
      low dose of ACE inhibitor initiated in acute myocardial infarction?
AB  - OBJECTIVE: Based on currently available clinical evidence, we should use high
      dose angiotensin converting enzyme inhibitor (ACE-I) for patients with acute
      myocardial infarction (MI), initiating it at incremental doses to avoid excessive
      hypotension. Recent animal studies with acute MI models failed to demonstrate the
      superiority of the combination therapy of ACE-I and angiotensin receptor blocker
      (ARB) to high-dose ACE-I treatment with comparable blood pressure reductions,
      which however might be attributed to the initiation of the targeted doses from
      the beginning. The aim of this study was to compare the effect of increasing the
      dose of ACE-I with that of adding ARB following a relatively low dose of ACE-I on
      the survival and left ventricular (LV) remodeling after MI. METHODS: Rats
      underwent left coronary artery ligation and were treated with either ACE-I
      temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after
      the surgery. The rats treated with temocapril were further randomly assigned to
      receive either high-dose temocapril (10 mg/kg/day) or combination therapy
      (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for
      another 6 weeks. RESULTS: Both treatments similarly reduced the blood pressure,
      improved survival and ameliorated LV enlargement. In contrast, several parameters
      of LV function were significantly ameliorated only by the high-dose ACE-I but not
      by the combination therapy. CONCLUSIONS: After the initiation of a relatively low
      dose of ACE-I in acute MI, increasing the dose of ACE-I or adding ARB may equally
      improve survival and LV remodeling in the setting of an equal hypotensive effect.
      Further study with a longer treatment protocol is required to determine whether
      the several favorable effects on LV function elicited only by the high-dose ACE-I
      treatment provide further beneficial effects on survival and LV remodeling
      compared with the combination therapy.

PMID- 12798436
TI  - The PPARgamma-activator rosiglitazone does not alter remodeling but increases
      mortality in rats post-myocardial infarction.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      activators may be beneficial in heart failure due to their metabolic and
      antihypertrophic effects, but these agents can cause oedema. We hypothesized
      that, on balance, the PPARgamma activator rosiglitazone would be beneficial in
      heart failure post-myocardial infarction. METHODS AND RESULTS: Rosiglitazone (3
      mg/kg/day p.o.) given to male Wistar rats for 14 days, caused a 31% increase in
      left ventricular (LV) dP/dt(max) (P<0.05 vs. placebo). A separate group of rats
      was subjected to sham (SH) or coronary artery ligation and randomised to:
      untreated (UT); rosiglitazone 3 mg/kg/day (R); captopril, 2 g/l in drinking water
      (C); captopril+rosiglitazone (C+R). Mean LV infarct sizes were similar for all
      groups at 40+/-2%. After 8 weeks, echocardiographic ejection fractions were 82+/
      3, 40+/-3, 50+/-2*, 49+/-2, 50+/-3% for SH, UT, R, C and C+R groups, respectively
      (*P<0.05 vs. UT). Captopril prevented LV dilatation, but rosiglitazone did not.
      In vivo hemodynamics showed that only UT had significantly elevated LV end
      diastolic pressures and reduced +dP/dt(max), with R partially, and C and C+R
      almost completely preventing the increase in LVEDP. Captopril, but not
      rosiglitazone, significantly reduced LV hypertrophy [LV/bw; 1.97+/-0.09 (SH),
      2.15+/-0.04 (UT), 2.10+/-0.05 (R), 1.81+/-0.04* (C), 1.88+/-0.07 (C+R); *(P<0.05
      vs. UT)]. Rosiglitazone increased 8-week mortality, which was 26% for R and 19%
      for C+R compared with 0% for UT and C (P=0.03 vs. UT). CONCLUSIONS: Rosiglitazone
      did not modulate LV remodeling, but was associated with increased mortality post
      myocardial infarction (MI) in rats. The mechanisms require further study, but
      these results caution against use of PPARgamma activators in post-MI heart
      failure in non-diabetics.

PMID- 12798437
TI  - Differential regulation of xanthine and NAD(P)H oxidase by hypoxia in human
      umbilical vein endothelial cells. Role of nitric oxide and adenosine.
AB  - OBJECTIVES: Although in tissue injury following hypoxia/reoxygenation (H/R) an
      increased endothelial formation of superoxide anions (O(2)(-)) plays an important
      role, it is still not fully understood which of the potential enzymatic sources
      of endothelial O(2)(-) are crucially involved. In this study, we particularly
      examined the activities of NAD(P)H oxidase and xanthine oxidase (XO) after 8 h of
      exposure to mild hypoxia. We further studied whether enzyme activities can be
      modified by NO and adenosine during hypoxic treatment. METHODS AND RESULTS: In
      human umbilical vein endothelial cells O(2)(-) production was measured
      immediately after exposure to hypoxia ('early reoxygenation') or after 2 h of
      reoxygenation at normoxic conditions ('late reoxygenation'). In the early
      reoxygenation phase the O(2)(-) production was attenuated by 28.5% while it was
      enhanced by 58.2% after late reoxygenation. Using specific inhibitors of NAD(P)H
      oxidase and XO, gp91ds-tat and oxypurinol, respectively, we show that the
      constitutively active NAD(P)H oxidase was blocked following hypoxia while XO was
      activated. The presence of NO during hypoxia had no effect on NAD(P)H oxidase
      activity but it significantly inhibited the activation of XO. Inhibition of XO
      activation was, at least in part, caused by the release of adenosine from
      endothelial cells which induces an increased formation of NO by its A1 and A2
      receptors. CONCLUSION: Our results indicate that during exposure to mild hypoxia
      for 8 h, a change in the enzymatic source of endothelial O(2)(-) occurs: a
      prolonged inhibition of NAD(P)H oxidase was found while an enhanced activity of
      XO occurs in the reoxygenation phase. These results suggest that different
      strategies of antioxidant therapy should be taken into consideration in oxidative
      stress related to chronic hypoxia when compared to normoxic atherosclerotic
      tissues with an activated vascular NAD(P)H oxidase as the main source of O(2)(-).

PMID- 12798438
TI  - Immunohistochemical localization of endothelial cell-derived lipase in
      atherosclerotic human coronary arteries.
AB  - OBJECTIVE: A novel lipoprotein lipase (LPL)-like gene, endothelial cell-derived
      lipase (EDL), was recently cloned from vascular endothelial cells. The presence
      of LPL in the vascular wall has been implicated in the progression of
      atherosclerosis through the bridging function between lipoprotein particles and
      matrix proteoglycans to enhance lipoprotein uptake into the vascular wall. The
      aim of this study was to investigate the local expression of EDL in human
      coronary arteries. METHODS AND RESULTS: Human coronary arterial specimens from 10
      autopsied cases were examined by immunohistochemistry with polyclonal antibodies
      against specific synthetic EDL peptides. Immunohistochemical analysis revealed
      that EDL was expressed in endothelial cells and medial smooth muscle cells in non
      atherosclerotic coronary arteries. In addition, EDL was expressed in infiltrating
      cells within atheromatous plaques as well as endothelial and smooth muscle cells.
      Double labeling immunofluorescence confirmed EDL positive-cells were endothelial
      cells, smooth muscle cells and macrophages. EDL immunoreactivity was also
      detected in neovasculature within atheromatous plaques in atherosclerotic
      coronary arteries. CONCLUSIONS: These results suggest that EDL may have unique
      functional roles in the pathogenesis of coronary artery diseases such as
      atherosclerosis as well as in lipid metabolism in the vessel wall.

PMID- 12798439
TI  - Addition of the selective aldosterone receptor antagonist eplerenone to ACE
      inhibition in heart failure: effect on endothelial dysfunction.
AB  - OBJECTIVES: To investigate the effects of adding the selective aldosterone
      receptor antagonist eplerenone to ACE inhibition on endothelium-dependent
      vasodilation in rats with chronic heart failure (CHF). BACKGROUND: Addition of
      the non-selective aldosterone antagonist spironolactone to ACE-inhibitors reduces
      mortality and morbidity in CHF and improves endothelial vasomotor dysfunction,
      but is associated with considerable side-effects. METHODS: Starting 10 days after
      extensive myocardial infarction (MI) or sham-operation, Wistar rats were treated
      either with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight
      per day), the selective aldosterone receptor antagonist eplerenone (EPL, 100
      mg/kg per day) or a combination of both for 9 weeks. RESULTS: Maximum
      acetylcholine-induced, nitric oxide-dependent relaxation was significantly
      attenuated in aortic rings from rats with CHF compared with sham-operated animals
      (R(max) 55% vs. 87%). EPL alone slightly and TR significantly improved NO
      mediated relaxation (CHF-EPL 66%; CHF-TR: 78%), while treatment with both EPL and
      TR completely restored endothelium-dependent vasorelaxation (CHF-EPL-TR: 83%).
      Aortic superoxide formation was significantly increased in rats with CHF compared
      with sham-operated animals, but was normalised by treatment with EPL or TR-EPL.
      Expression of the endothelial nitric oxide synthase was decreased in CHF and
      normalised in all treatment groups. CONCLUSIONS: In experimental CHF, the
      selective aldosterone antagonist EPL reduced the increased vascular superoxide
      formation. Although a combination of TR and EPL normalised endothelium-dependent
      relaxation, ACE inhibition as a monotherapy was almost equally effective.

PMID- 12798440
TI  - Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite
      formation in rat hearts.
AB  - OBJECTIVE: We investigated the influence of experimental hyperlipidemia on the
      formation of cardiac NO, superoxide, and peroxynitrite (ONOO(-)) in rat hearts.
      METHODS: Wistar rats were fed 2% cholesterol-enriched diet or normal diet for 8
      weeks. Separate groups of normal and hyperlipidemic rats were injected twice
      intraperitoneally with 2 x 20 micromol/kg FeTPPS (5,10,15,20-tetrakis-[4
      sulfonatophenyl]-porphyrinato-iron[III]), a ONOO(-) decomposition catalyst, 24 h
      and 1 h before isolation of the hearts. RESULTS: A cholesterol diet significantly
      decreased myocardial NO content, however, myocardial Ca(2+)-dependent and Ca(2+)
      independent NO synthase activity and NO synthase protein level did not change.
      Myocardial superoxide formation and xanthine oxidase activity were significantly
      increased; however, cardiac superoxide dismutase activity did not change in the
      cholesterol-fed group. Dityrosine in the perfusate, a marker of cardiac ONOO(-)
      formation, and plasma nitrotyrosine, a marker for systemic ONOO(-) formation,
      were both elevated in hyperlipidemic rats. In cholesterol-fed rats, left
      ventricular end-diastolic pressure (LVEDP) was significantly elevated as compared
      to controls. Administration of FeTPPS normalized LVEDP in the cholesterol-fed
      group. CONCLUSION: We conclude that cholesterol-enriched diet-induced
      hyperlipidemia leads to an increase in cardiac ONOO(-) formation and a decrease
      in the bioavailability of NO which contributes to the deterioration of cardiac
      performance and may lead to further cardiac pathologies.

PMID- 12798441
TI  - Exogenous nitric oxide causes overexpression of TGF-beta1 and overproduction of
      extracellular matrix in human coronary smooth muscle cells.
AB  - OBJECTIVE: Nitric oxide (NO) is a major signalling molecule in the vascular
      system enhancing vascular smooth muscle cell relaxation and vasodilation. NO
      donors are the most frequently and repeatedly used drugs for relief from angina
      pectoris. METHODS: We investigated the effects of the synthetic NO donor DETA/NO
      on cultured human coronary smooth muscle cells. RESULTS: Cells exposed to 100
      microM DETA/NO for 48-72 h were channeled into a cell cycle-arrested hypertrophic
      growth status associated with overexpression of TGF-beta(1) on both the protein
      and mRNA levels. Increased TGF-beta(1) transcription and translation were
      associated with enhanced synthesis of extracellular matrix components including
      the collagen types I and III as shown by immunocytochemistry and enhanced
      incorporation of [3H]proline. Higher incorporation of [35S]sulfate into
      chondroitin/dermatan sulfate and heparan sulfate containing proteoglycans was
      observed in DETA/NO treated cells than in controls. The ratio of
      chondroitin/dermatan sulfate to heparan sulfate did not change significantly.
      CONCLUSIONS: Our results suggest a dual function of the overexpressed TGF
      beta(1). Overexpressed TGF-beta(1) could stabilize the fibrous cap overlaying
      atherosclerotic plaques due to the accumulation of extracellular matrix
      components. However, the findings could also support a proatherogenic role of TGF
      beta(1) resulting from the overexpression of LDL-binding proteoglycans.

PMID- 12798442
TI  - Relationship between type IV collagen degradation, metalloproteinase activity and
      smooth muscle cell migration and proliferation in cultured human saphenous vein.
AB  - The relationship between degradation of basement membranes, metalloproteinase
      (MMP) activity and smooth muscle cell (SMC) migration and proliferation has not
      been previously investigated in any intervention study. We used adenoviral
      overexpression of tissue inhibitors of metalloproteinases (TIMPs) in cultured
      human saphenous veins. By immunocytochemistry, the percentage of medial SMC
      surrounded by basement membrane type IV collagen (Coll-IV) decreased from 93+/-1
      to 77+/-4% and 82+/-1% (n=18, both P<0.001) after 7 and 14 days of culture,
      respectively, while all SMC that migrated to the neointima lacked Coll-IV.
      Overexpression of TIMP-1 or TIMP-3 significantly increased the percentage of
      medial SMC surrounded by Coll-IV (94+/-2 or 98+/-2%, respectively, both P<0.01
      vs. no treatment) and decreased the number of neointimal SMC. Some 44+/-18 and
      30+/-6%, respectively, of BrdU or PCNA labeled medial SMC remained surrounded by
      type IV collagen and this was not affected by overexpression of TIMP-1 or TIMP-3.
      We conclude that MMPs mediate loss of basement membrane and this is closely
      related to SMC migration. SMC proliferation does not require complete basement
      membrane degradation, which itself does not require MMPs in proliferating SMC.

PMID- 12798443
TI  - Increased arterial expression of a glycosylated haptoglobin isoform after balloon
      dilation.
AB  - OBJECTIVE: Haptoglobin is a novel cell migration factor that is expressed in
      arteries after sustained flow changes and involved in arterial restructuring.
      Arterial restructuring is the major determinant of arterial shrinkage after
      balloon dilation. Although the function of extrahepatic haptoglobin expression is
      not yet understood, local haptoglobin expression may provide the tissue with
      functionally different haptoglobin due to post-translational modifications. We
      hypothesized that haptoglobin expression is increased during arterial
      restructuring after balloon dilation and compared glycosylation patterns between
      arterial and liver haptoglobin. METHODS: Arterial haptoglobin expression was
      studied in rabbits at 0, 2, 7, 14 and 28 days after balloon dilation (n=36) using
      real-time polymerase chain reaction, Western blotting and in situ hybridization.
      Two-dimensional gel electrophoresis and lectin affinity blotting were used to
      identify liver and arterial haptoglobin glycoforms. RESULTS: Arterial haptoglobin
      mRNA (5.7-fold, P=0.01) and protein levels (1.4-fold, P=0.01) were increased
      after balloon dilation whereas liver haptoglobin expression remained constant.
      Haptoglobin was expressed in the adventitia of balloon dilated rabbit arteries,
      which was confirmed in human atherosclerotic arteries. Comparison between liver
      and arterial haptoglobin demonstrated the expression of artery-specific
      haptoglobin glycoforms. CONCLUSIONS: This study demonstrates that arterial
      haptoglobin expression is increased early after balloon dilation whereas liver
      haptoglobin expression does not change. Furthermore, arterial haptoglobin
      consists of an unique set of glycoforms compared to haptoglobin produced in the
      liver.

PMID- 12798444
TI  - Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a
      receptor-based biosensor model.
AB  - Proteoheparan sulfate can be adsorbed onto a methylated silica surface in a
      monomolecular layer via its transmembrane hydrophobic protein core domain. Due to
      electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched
      out into the blood substitute solution, thereby representing a receptor site for
      specific lipoprotein binding through basic amino acid-rich residues within their
      apolipoproteins. The binding process was studied by ellipsometric techniques
      suggesting that HDL has a high binding affinity and a protective effect on
      interfacial heparan sulfate proteoglycan layers with respect to LDL and Ca(2+)
      complexation. LDL was found to be deposited strongly at the proteoheparan sulfate
      coated surface, particularly in the presence of Ca(2+), apparently through
      complex formation 'proteoglycan-low density lipoprotein-calcium'. This ternary
      complex build-up may be interpreted as arteriosclerotic nanoplaque formation on
      the molecular level responsible for the arteriosclerotic primary lesion. In a
      receptor-based biosensor application, this system was tested on its reliability
      to unveil possible acute pleiotropic effects of the lipid lowering drug
      fluvastatin. The VLDL/IDL/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high
      risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed the
      start of arteriosclerotic nanoplaque formation at a normal blood Ca(2+)
      concentration, with a strong increase at higher Ca(2+) concentrations. Nanoplaque
      formation and size of the HDL-containing lipid fraction remained well below that
      of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the
      patient (one single 80 mg slow release matrix tablet) or in a 2-month medication
      regimen, markedly slowed down this process of ternary aggregational nanoplaque
      build-up and substantially inhibited nanoplaque size development at all Ca(2+)
      concentrations used. The acute action gave no significant change in lipid
      concentrations of the patient. Furthermore, after nanoplaque generation,
      fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size.
      These immediate effects of fluvastatin have to be taken into consideration when
      interpreting the clinical outcome of long-term studies.

PMID- 12798445
TI  - Relaxation by urocortin of rat renal arteries: effects of diabetes in males and
      females.
AB  - OBJECTIVE: Urocortin is a peptide structurally related to corticotropin releasing
      factor (CRF), and the present study was performed to examine the effects of
      diabetes mellitus on the relaxation by urocortin of renal arteries from males and
      females. METHODS: The response to urocortin was studied in isolated segments, 2
      mm long, from renal arteries, from male and female, control (normoglycemic) and
      streptozotocin-induced diabetic rats. RESULTS: In the renal arterial segments
      precontracted with endothelin-1, urocortin produced concentration-dependent
      relaxation, that was not different between males and females. Diabetes reduced
      the relaxation in renal arteries from females but not in those from males. The
      potassium channel blocker charybdotoxin (10(-7) M) reduced the relaxation to
      urocortin of renal arteries from normoglycemic males and females. The
      cyclooxygenase inhibitor meclofenamate did not modify the relaxation to urocortin
      in renal arteries from normoglycemic males or females. The inhibitor of nitric
      oxide synthesis N(W)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) reduced the
      relaxation to urocortin in renal arteries from normoglycemic females, but not in
      renal arteries from normoglycemic males. Neither charybdotoxin, L-NAME or
      meclofenamate modified the relaxation to urocortin of renal arteries from
      diabetic females. CONCLUSION: These results suggest that urocortin produces a
      marked vasodilation of renal arteries, which may be mediated by nitric oxide in
      females and by activation of potassium channels in both genders, and is reduced
      by diabetes in renal arteries from females.

PMID- 12798446
TI  - Formation of apolipoprotein AI-phosphatidylcholine core aldehyde Schiff base
      adducts promotes uptake by THP-1 macrophages.
AB  - OBJECTIVE: High-density lipoprotein (HDL) is believed to protect against
      development of atherosclerosis by inhibiting the accumulation of oxidized lipids
      in low-density lipoprotein (LDL). Paradoxically, HDL lipid is more susceptible to
      oxidation than LDL lipid. In the present study, we examined the effect of
      oxidized phospholipids on the uptake of HDL by macrophages. METHODS AND RESULTS:
      Oxidation of HDL increased formation of phosphatidylcholine core aldehydes that
      was paralleled by increased covalent binding of phospholipids to HDL protein from
      0.96+/-0.44 to 8.5+/-1.76 phosphorus/HDL protein (mol/mol). Incubation of
      apolipoprotein AI with synthetically prepared phosphatidylcholine core aldehydes,
      1-palmitoyl-2-[5-oxo]valeroyl-sn-glycero-3-phosphocholine or 1-palmitoyl-2-[9
      oxo] nonanoyl-sn-glycero-3-phosphocholine, significantly increased the
      phosphorus:apolipoprotein AI ratio from 1.1+/-0.5 to 7.2+/-2.0 and from 0.9+/-0.6
      to 8.5+/-0.8, respectively. The binding and uptake of phosphatidylcholine core
      aldehyde-apolipoprotein AI proteoliposomes, by THP-1 macrophages, was similar to
      that observed for oxidized HDL and oxidized LDL. CONCLUSION: We conclude that
      oxidation of HDL increased formation of phosphatidylcholine core aldehyde
      apolipoprotein AI Schiff base adducts and enhanced uptake of oxidized HDL by THP
      1 macrophages.

PMID- 12798447
TI  - A different view on human albumin.

PMID- 12798449
TI  - Decompensated heart failure: symptoms, patterns of onset, and contributing
      factors.
AB  - PURPOSE: To examine the time course, contributing factors, and patient responses
      to decompensated heart failure. METHODS: We studied consecutive patients admitted
      to a public general hospital with a diagnosis of heart failure. Using a timeline
      follow-back technique, a nurse interviewer administered a questionnaire shortly
      after admission, exploring knowledge of a heart failure diagnosis, the symptoms
      and time course of decompensation, and patient responses to worsening symptoms.
      RESULTS: Of 87 patients, 83 (95%) consented to be interviewed. Only 49 (59%) were
      aware of the diagnosis of heart failure. Symptoms associated with decompensation
      included dyspnea in 81 patients (98%), edema in 64 patients (77%), and weight
      gain in 34 patients (41%). Onset of worsening of these symptoms was noted a mean
      (+/- SD) of 12.4 +/-1.4 days before admission for edema, 11.3 +/-1.6 days for
      weight gain, and 8.4 +/- 0.9 days for dyspnea. Forty-two patients (57%) reported
      missing or skipping medication because of various factors, particularly missed
      outpatient appointments. CONCLUSION: Using a timeline follow-back interview, we
      identified a period of days to weeks between the onset of worsening symptoms and
      hospital admission for heart failure decompensation. This pattern suggests that
      there is a time window between symptom exacerbation and admission during which
      earlier access and intervention might prevent hospitalization in these patients.
      Medication lapses continue to be an important preventable cause of decompensation
      leading to admission.

PMID- 12798450
TI  - Clinical evaluation for cancer in patients with involuntary weight loss without
      specific symptoms.
AB  - PURPOSE: There is no established diagnostic approach to rule out cancer in
      patients who present with involuntary weight loss in the absence of other
      symptoms (isolated involuntary weight loss). We sought to evaluate the efficiency
      of various diagnostic studies used in these patients. METHODS: We studied 306
      patients referred to an urban tertiary care teaching hospital for isolated
      involuntary weight loss, 276 of whom were followed for at least 1 year or until a
      final diagnosis was reached. We collected data about the diagnostic approach, the
      causes of unintentional weight loss, and survival. RESULTS: Of the 276 patients,
      104 (38%) had cancer, mainly of the digestive system (54%, n = 56). The first
      diagnostic clue usually came from routine blood tests (complete blood count,
      erythrocyte sedimentation rate, and a biochemical profile), which led to a more
      targeted diagnostic procedure, such as abdominal ultrasonography, computed
      tomography, and gastrointestinal endoscopy. Only 2 patients with cancer had
      normal results in all of these tests. Nine of the patients with cancer were not
      detected during the initial evaluation. Median survival was 2 months among
      patients with cancer, and only 9 survived longer than 1 year. CONCLUSION: These
      results suggest that a clinical approach, including routine laboratory tests
      (complete blood count, erythrocyte sedimentation rate, and serum albumin,
      aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, and
      lactate dehydrogenase levels) and abdominal ultrasonography, seems to be
      appropriate for detecting the majority of cases of cancer among patients with
      isolated involuntary weight loss.

PMID- 12798451
TI  - Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients.
AB  - BACKGROUND: Little is known about the molecular mechanisms responsible for the
      development of glaucoma, the leading cause of irreversible blindness worldwide.
      Some investigators have hypothesized that oxidative damage may be involved. We
      evaluated oxidative deoxyribonucleic acid (DNA) damage, in terms of 8-hydroxy-2'
      deoxyguanosine (8-OH-dG), in the eyes of glaucoma patients. METHODS: Levels of 8
      OH-dG were measured in the trabecular meshwork region from 42 patients with
      glaucoma and 45 controls of similar age and sex. Genotypes of glutathione S
      transferase isoenzymes (GSTM1 and GSTT1) were assessed by polymerase chain
      reaction in the same DNA samples. RESULTS: Levels of 8-OH-dG were significantly
      higher in glaucoma patients than in controls. Oxidative DNA damage in patients
      with glaucoma correlated significantly with intraocular pressure; in patients
      with primary open-angle glaucoma, it also correlated with visual field defects.
      GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels.
      Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1
      positive subjects. The GSTM1-null genotype was significantly more common in
      patients with primary open-angle glaucoma than in controls. CONCLUSION: Oxidative
      DNA damage is significantly increased in the trabecular meshwork of glaucoma
      patients. GSTM1 gene deletion, which has been associated with an increased risk
      of cancer at various sites and molecular lesions in atherosclerosis, predisposes
      to more severe oxidative DNA damage in glaucoma patients. These findings may
      contribute to understanding the pathogenesis of glaucoma and may be useful in the
      prevention and treatment of this disease.

PMID- 12798452
TI  - HLA-DRB1 status affects endothelial function in treated patients with rheumatoid
      arthritis.
AB  - PURPOSE: To examine endothelial function in rheumatoid arthritis patients and to
      assess whether clinical or genetic factors affect the development of endothelial
      dysfunction. METHODS: Fifty-five patients fulfilling the 1987 American College of
      Rheumatology classification criteria for rheumatoid arthritis were recruited from
      Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated
      for at least 5 years, including current treatment with one or more disease
      modifying antirheumatic drugs. Patients with diabetes mellitus, renal
      insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-,
      and ethnically matched controls were also studied. Endothelium-dependent
      (postischemia) and -independent (postnitroglycerin) vasodilatation were measured
      by brachial ultrasonography. Patients were genotyped for human leukocyte antigen
      (HLA)-DRB1. RESULTS: Patients had decreased endothelium-dependent vasodilatation
      (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001).
      There were no differences in endothelium-independent vasodilatation. Clinical
      features were not associated with endothelial dysfunction. Endothelium-dependent
      vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA
      DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients
      (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA
      DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients
      (4.4% +/- 4.9%; P = 0.01). CONCLUSION: Patients with chronically treated
      rheumatoid arthritis had evidence of endothelial dysfunction, especially those
      with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1
      status may be a predictor of cardiovascular risk in these patients.

PMID- 12798453
TI  - The effects of adjuvant chemotherapy on bone density in postmenopausal women with
      early breast cancer.
AB  - PURPOSE: Adjuvant chemotherapy for breast cancer can have adverse effects on
      bone. We investigated the effects of adjuvant chemotherapy on bone mineral
      density in postmenopausal women with early-stage breast cancer. METHODS: We
      performed a chart review of all our breast center patients who had spine or hip
      bone density measured by dual-energy X-ray absorptiometry at our institution
      after treatment for stage I or II breast cancer. Patients who had other causes of
      metabolic bone disease were excluded. Multivariate regression analysis was used
      to adjust for confounding factors. Results were expressed as age-adjusted
      standard deviation units (Z scores). RESULTS: Of the 130 eligible women, 36 (28%)
      received adjuvant chemotherapy and 94 (72%) did not. Mean adjusted bone density
      scores in both the hip (0.65 SD units; 95% confidence interval [CI]: 0.32 to 0.98
      SD units; P = 0.0002) and spine (0.60 SD units; 95% CI: 0.01 to 1.19 SD units; P
      = 0.05) were significantly lower in patients who had received adjuvant
      chemotherapy compared with those who had not. CONCLUSION: Women who were
      postmenopausal when they developed breast cancer and who received adjuvant
      chemotherapy had lower bone density than those who did not. Whether this effect
      is caused by adjuvant chemotherapy remains to be determined.

PMID- 12798455
TI  - Hawthorn extract for treating chronic heart failure: meta-analysis of randomized
      trials.
AB  - The aim of this meta-analysis was to assess the evidence from rigorous clinical
      trials of the use of hawthorn extract to treat patients with chronic heart
      failure. We searched the literature using MEDLINE, EMBASE, the Cochrane Library,
      CINAHL, CISCOM, and AMED. Experts on and manufacturers of commercial preparations
      containing hawthorn extract were asked to contribute published and unpublished
      studies. There were no restrictions about the language of publication. Two
      reviewers independently performed the screening of studies, selection,
      validation, data extraction, and the assessment of methodological quality. To be
      included, studies were required to state that they were randomized, double-blind,
      and placebo controlled, and used hawthorn extract monopreparations. Thirteen
      trials met all inclusion criteria. In most of the studies, hawthorn was used as
      an adjunct to conventional treatment. Eight trials including 632 patients with
      chronic heart failure (New York Heart Association classes I to III) provided data
      that were suitable for meta-analysis. For the physiologic outcome of maximal
      workload, treatment with hawthorn extract was more beneficial than placebo
      (weighted mean difference, 7 Watt; 95% confidence interval [CI]: 3 to 11 Watt; P
      < 0.01; n = 310 patients). The pressure-heart rate product also showed a
      beneficial decrease (weighted mean difference, -20; 95% CI: -32 to -8; n = 264
      patients) with hawthorn treatment. Symptoms such as dyspnea and fatigue improved
      significantly with hawthorn treatment as compared with placebo. Reported adverse
      events were infrequent, mild, and transient; they included nausea, dizziness, and
      cardiac and gastrointestinal complaints. In conclusion, these results suggest
      that there is a significant benefit from hawthorn extract as an adjunctive
      treatment for chronic heart failure.

PMID- 12798454
TI  - Differences in mortality among patients with community-acquired pneumonia in
      California by ethnicity and hospital characteristics.
AB  - PURPOSE: To determine ethnic disparities in mortality for patients with community
      acquired pneumonia, and the potential effects of hospital characteristics on
      disparities, we compared the risk-adjusted mortality of white, African American,
      Hispanic, and Asian American patients hospitalized for community-acquired
      pneumonia. METHODS: We studied patients discharged with community-acquired
      pneumonia in 1996 from an acute care hospital in California (n = 54,874).
      Logistic regression models were used to examine the association between ethnicity
      and hospital characteristics and 30-day mortality after adjusting for clinical
      characteristics. RESULTS: The overall 30-day mortality was 12.2%. After
      adjustment for demographic, clinical, and hospital characteristics, Hispanic
      (odds ratio [OR] = 0.81; 95% confidence interval [CI]: 0.73 to 0.90) and Asian
      American patients (OR = 0.88; 95% CI: 0.77 to 1.00) had lower mortality than did
      white patients, whereas African Americans had a similar mortality to whites (OR =
      0.93; 95% CI: 0.83 to 1.06). There were no overall differences in mortality by
      hospital characteristics (i.e., teaching status, rural location, and public or
      district hospital). CONCLUSION: Hispanics and Asian Americans have a lower risk
      of death from community-acquired pneumonia than whites in California. No overall
      differences in mortality were observed by hospital characteristics.

PMID- 12798456
TI  - Simian virus 40 in human cancers.
AB  - BACKGROUND: Many studies have reported the presence of simian virus 40 (SV40)
      deoxyribonucleic acid (DNA) or protein in human brain tumors and bone cancers,
      malignant mesothelioma, and non-Hodgkin's lymphoma. However, the small samples
      and lack of control groups in some reports have made it difficult to assess their
      reliability. METHODS: Studies were included in this analysis if they met the
      following criteria: original studies of patients with primary brain tumors and
      bone cancers, malignant mesothelioma, or non-Hodgkin's lymphoma; the
      investigation of SV40 was performed on primary cancer specimens; the analysis
      included a control group; and the same technique was used for cases and controls.
      Included reports were published from 1975 to 2002. RESULTS: Thirteen studies
      fulfilled the criteria for the investigation of primary brain cancers (661 tumors
      and 482 control samples). Specimens from patients with brain tumors were almost
      four times more likely to have evidence of SV40 infection than were those from
      controls (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 2.6 to 5.8). The
      association was even stronger for mesothelioma (OR = 17; 95% CI: 10 to 28; based
      on 15 studies with 528 mesothelioma samples and 468 control samples) and for bone
      cancer (OR = 25; 95% CI: 6.8 to 88; based on four studies with 303 cancers and
      121 control samples). SV40 DNA was also more frequent in samples from patients
      with non-Hodgkin's lymphoma (OR = 5.4; 95% CI: 3.1 to 9.3; based on three studies
      with 301 cases and 578 control samples) than from controls. CONCLUSION: These
      results establish that SV40 is associated significantly with brain tumors, bone
      cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Studies are needed
      to assess current prevalence of SV40 infections.

PMID- 12798457
TI  - Serum homocysteine levels and mortality in outpatients with or without coronary
      artery disease: an observational study.

PMID- 12798458
TI  - Sharps-related injuries in health care workers: a case-crossover study.

PMID- 12798459
TI  - Decompensated heart failure revisited.

PMID- 12798460
TI  - A new clue to glaucoma pathogenesis.

PMID- 12798461
TI  - Rushing, distraction, and anger.

PMID- 12798462
TI  - Hawthorn extract: is it time to turn over a new leaf?

PMID- 12798463
TI  - Cases from the Osler Medical Service at Johns Hopkins University.

PMID- 12798464
TI  - Reason to screen for prostate cancer based on selective referencing.

PMID- 12798466
TI  - Subacute motor weakness and left renal mass.

PMID- 12798467
TI  - Pericardial and pleural effusion in giant cell arteritis.

PMID- 12798468
TI  - The research community now and in the future: APM's recommendations for NIH
      priorities.

PMID- 12798469
TI  - Hormone replacement therapy and hypercoagulability. Results from the Prospective
      Collaborative Danish Climacteric Study.
AB  - OBJECTIVE: To assess the influence of a variety of HRT regimens on the
      haemostatic balance using markers of fibrin turnover and inhibitors of
      coagulation. DESIGN: An open randomised study allocating women to either a
      control group or five different HRT treatment groups. SETTING: Gentofte Hospital,
      Hellerup, and Rigshospitalet, Copenhagen, Denmark. POPULATION: One hundred and
      forty-nine postmenopausal women without previous venous thromboembolic disease.
      METHODS: Prothrombin fragment 1+2 (F(1+2)), fibrin degradation products,
      antithrombin, protein C, total protein S and activated protein C-normalised ratio
      were measured at baseline and after 6 and 12 months of HRT in six groups of
      healthy postmenopausal women: (A). no HRT (reference group), (B). continuous
      oestradiol valerate (E(2)V) plus cyproterone acetate, (C). cyclic E(2)V plus
      cyproterone acetate, (D). continuous combined oestrogen (E(2)) plus norethindrone
      acetate, (E). E(2) combined with local delivery of levonorgestrel and (F). E(2)V
      plus medroxyprogesterone. HRT-induced changes in the concentration of inhibitors
      of coagulation and markers of fibrin turnover during 12 months of treatment.
      RESULTS: Significant decreases of antithrombin and protein S were found in all
      treatment groups, of protein C in Groups C, D, E and F and of activated protein C
      normalised ratio in Groups E and F. Fibrin degradation products increased after
      three months of treatment, whereas F(1+2) was persistently increased after three
      months in Group F. The cumulative response of antithrombin was significantly
      lower in Groups D, E and F than in the reference group. The cumulative response
      of protein S and activated protein C-normalised ratio was lower, whereas that of
      F(1+2) was significantly higher in Group F than in the reference group.
      CONCLUSION: HRT reduces the inhibitory potential of coagulation significantly.
      The effect is related to the type of E(2)/progestin combination administered, but
      seems to be oestrogen-derived as the most pronounced effect is found with only
      quarterly progestin intake. Such procoagulant activity of HRT may well translate
      into clinical manifestations in thrombosis-prone individuals.

PMID- 12798470
TI  - Increased vaginal bleeding and psychological distress: a longitudinal study of
      their relationship in the community.
AB  - OBJECTIVE: To explore the temporal relationship between the development of self
      reported symptoms of vaginal bleeding and the development of psychological
      distress among women in the community. DESIGN: Prospective cohort study using
      postal surveys at baseline and at 6 and 12 months. SETTING: An urban four-partner
      general practice with 10000 registered patients. POPULATION: All women aged 18-54
      years on the practice age-sex register. METHODS: Baseline postal questionnaire
      with follow up questionnaires sent at 6 and 12 months. MAIN OUTCOME MEASURES: The
      associations between the development of heavy periods and psychological distress.
      RESULTS: Two thousand and four hundred and thirty-five baseline questionnaires
      were sent out with an initial response rate of 76%. One thousand and five hundred
      and thirteen women (62%) responded to all three questionnaires. Women with
      psychological distress at baseline were more likely to develop heavy periods 6
      months later than women without distress (adjusted odds ratio 1.87, 95% CI 1.15,
      3.02). Women with heavy periods at baseline were no more likely to develop
      psychological distress 6 months later than women with non-heavy periods (adjusted
      odds ratio 1.09, 95% CI 0.73, 1.63). Similar findings existed with respect to
      intermenstrual bleeding and postcoital bleeding. Results of the 12-month analysis
      were similar. CONCLUSION: In the community, psychological distress appears to
      influence the future self-reporting of heavy periods and other symptoms of
      vaginal bleeding.

PMID- 12798471
TI  - Gestational trophoblastic disease in the Asian population of Northern England and
      North Wales.
AB  - OBJECTIVE: To determine the incidence and trends of gestational trophoblastic
      disease in the Asian population of Northern England and North Wales.A prospective
      observational study. SETTING: Trophoblastic Screening and Treatment Centre,
      Weston Park Hospital. POPULATION: A total of 3660 women registered with
      gestational trophoblastic disease between 1991 and 1999. MAIN OUTCOME MEASURES:
      1. The incidence of gestational trophoblastic disease in Asian and non-Asian
      population. 2. Trend in incidence over study period. RESULTS: Three hundred and
      twenty-two Asian patients were registered. The incidence of gestational
      trophoblastic disease in the northern part of England and Wales averaged 1 per
      714 live births. The incidence of gestational trophoblastic disease in the Asian
      population was 1.95 times higher than in the non-Asian population (1 per 387 live
      births vs 1 per 752 live births). There was an excess of molar pregnancies in the
      extreme maternal age groups; the incidence in these women was twice as high as in
      the whole reproductive cohort. The ratio of partial to complete hydatidiform mole
      increased from 0.9 in the lower age to 2.6 in the older age group. There appeared
      to be a slowly rising trend in the incidence of gestational trophoblastic
      disease; the increase was higher in the Asian than in the non-Asian population.
      The ratio of partial to complete moles increased with age in both populations.
      CONCLUSION: Asian women are at increased risk of having molar pregnancies. Molar
      pregnancies are more common at the extremes of reproductive age. The setting up
      of regional or national registration centres has helped to provide more accurate
      estimates of the true incidence of the disease.

PMID- 12798472
TI  - Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The
      Netherlands.
AB  - OBJECTIVE: To investigate whether a desire for pregnancy changed after etoposide,
      methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO) treatment
      for gestational trophoblastic disease and whether the incidence of infertility
      and adverse pregnancy outcome differed from the general population. DESIGN: A
      cohort study was performed. Data were collected from hospital records and
      questionnaires. SETTING: The study was carried out in referral hospitals in The
      Netherlands. POPULATION: All women registered by the Dutch Working Party on
      Trophoblastic Disease and treated with EMA/CO were included. METHODS: A
      questionnaire was sent to all surviving patients treated with EMA/CO from 1986
      until 1997. Women who underwent a hysterectomy were excluded from the study. MAIN
      OUTCOME MEASURE: Pregnancy outcome and pregnancy wish after chemotherapy.
      RESULTS: Fifty patients were treated with EMA/CO. In 86%, a complete remission
      was achieved. A questionnaire was sent to 33 patients. Response rate was 82%
      (27/33). After EMA/CO, 18 of the patients experienced a regular menstrual cycle.
      Three patients had an amenorrhoea. Fourteen patients had a pregnancy wish. Twelve
      patients conceived; 21 pregnancies occurred. Sixteen pregnancies were term
      deliveries. Two pregnancies ended in a miscarriage and two congenitally abnormal
      children were delivered prematurely. CONCLUSION: After EMA/CO, 86% of women with
      a pregnancy wish achieved pregnancy. However, women can be so anxious about a new
      pregnancy that they refrain from it. A causative relation between the two
      congenitally abnormal children and EMA/CO cannot be determined because of the
      small sample. The rate of miscarriages is not higher than in the general
      population. We can reassure patients that pregnancy after EMA/CO has a high
      probability of success and a favourable outcome. To diminish the fear of getting
      pregnant in some patients, psychosocial care should be considered in addition to
      medical care.

PMID- 12798473
TI  - The 24-hour pad test in continent women and men: normal values and cyclical
      alterations.
AB  - OBJECTIVE: To obtain control values for the 24-hour pad test in a wide age range
      of continent women using accurate weighing scales and to compare the results
      obtained from pantyliners and pads in women and men. DESIGN: Prospective
      anonymous study. SETTING: A Sydney Tertiary Urogynaecology Unit. POPULATION: One
      hundred and forty continent women and 14 continent men. METHODS: A 24-hour pad
      test was performed in 120 continent women of widely varying ages, in whom
      hormonal status and exercise habits were documented. These continent women wore a
      standardised pantyliner for 24 hours and a high precision beam balance (accuracy
      0.1 g) was used to measure the loss on the pad. To assess any variation in pad
      weights with differing pads, 20 female volunteers undertook the 24-hour test
      firstly with pantyliners then larger pads. To understand evaporative qualities of
      the two types of pads, one male wore each type of pad, instilled with 5 mL normal
      saline for eight hours overnight. Furthermore, to understand the contribution of
      vaginal secretions, a group of male volunteers performed a 24-hour test with
      pantyliners followed by pads. MAIN OUTCOMES MEASURES: Pad weight, with regard to
      hormonal status, exercise, pad type and gender. The median age of subjects was 48
      (interquartile range [IQR] 32-60), with a median pad weight gain of 0.3 g (IQR
      0.2-0.6; 95th centile 1.3 g). Subgroup analysis showed no significant trends for
      pad loss in relation to menopause status, use of hormone replacement therapy or
      hormonal contraception and exercise status during the 24-hour period. Control
      values for pantyliners were not significantly different from those for continence
      pads. In addition, normal values in 14 males showed similar results, regardless
      of pad type. CONCLUSIONS: The response rate of 39% might limit the applicability
      of the results. However, our finding that women lose only 0.3 g of vaginal
      secretions in 24 hours is much lower than previously reported. This might arise
      from the use of a highly accurate beam balance and the recruitment of a large
      sample of women with widely varying ages. This result might lower the threshold
      for objective diagnosis of urinary incontinence and alters the pad test
      definition of 'cure'.

PMID- 12798474
TI  - Clinical manifestations and abnormal laboratory findings in pregnant women with
      primary cytomegalovirus infection.
AB  - OBJECTIVE: To compare the clinical manifestations and laboratory abnormalities
      associated with primary cytomegalovirus (CMV) infection in pregnancy with
      recurrent and non-active CMV infection (controls). DESIGN: A prospective cohort
      study. SETTING: Rome, Latium and other Italian regions. POPULATION: Three hundred
      and sixteen pregnant women with CMV infection: 102 had primary infection, 105 had
      recurrent infection and 109 with non-active infection were followed up as
      controls. METHODS: CMV diagnosis was based on serological examinations (CMV IgG,
      IgM and IgG avidity) and detection of CMV DNA by polymerase chain reaction in
      maternal serum, urine and cervical samples. The clinical history and laboratory
      evaluations were carried out at enrollment and at each subsequent visit, every
      one to three months. MAIN OUTCOME AND MEASURES: Identification of clinical and
      laboratory indicators of primary CMV infection in pregnancy. RESULTS: Compared
      with women with recurrent or non-active infection, women with primary infection
      had a statistically significant higher prevalence of fever, asthenia, myalgia and
      flu-like syndrome (P < 0.001). In particular, relevant symptomatology was
      observed in 32 women (31.4%), of whom 25 had flu-like syndrome and 7 persistent
      fever as a single manifestation. Moreover, women with primary infection showed a
      significantly increased rate of lymphocytes >or=40% (39.2% vs 5.7% or 3.7%,
      respectively, P < 0.001) and elevated aspartate aminotransferase and/or alanine
      aminotransferase levels (35.3% vs 3.9% or 0.9%, respectively, P < 0.001):
      lymphocytosis and/or increased aminotransferases occurred in 53 patients (52%).
      In total, clinical manifestations and/or laboratory abnormalities occurred in 61
      women with primary infection (59.8%) compared with 20 with recurrent infection
      (19%) and 13 controls (11.9%) (P < 0.001). CONCLUSION: Clinical manifestations
      (i.e. flu-like syndrome, fever) and abnormal laboratory findings (i.e.
      lymphocytes >or=40%, elevated aminotransferases) may suggest the presence of
      primary CMV infection and should prompt subsequent virological investigations.

PMID- 12798475
TI  - A prospective study of the role of ultrasound in the management of adnexal masses
      in pregnancy.
AB  - OBJECTIVE: To assess the clinical relevance of adnexal masses in pregnancy and
      the usefulness of ultrasound in their management. DESIGN: A prospective study on
      pregnancy complicated by adnexal masses. SETTING: Department of Obstetrics and
      Gynaecology in Italy. POPULATION: 6636 women with pregnancy in utero followed in
      our clinic from January 1996 to December 1999. METHODS: From 1996 to 1999, all
      ovarian cysts with a diameter exceeding 3 cm were prospectively recorded and
      followed. The management was expectant except in case of symptoms or suspected
      malignant features. Cysts suggestive of borderline tumours were treated
      expectantly. MAIN OUTCOME MEASURES: Clinical relevance of adnexal masses in
      pregnancy, the outcome of these pregnancies and the usefulness of ultrasound
      examination in their management. RESULTS: We detected 82 cysts in 79 of 6636
      women (1.2 in 100 term pregnancies). Sixty-eight women were asymptomatic at the
      time of diagnosis, whereas 11 (13.9%) were diagnosed because of pain. Diagnosis
      occurred in the first trimester for 57 cases and in the second or third trimester
      in 22 (27.8%). One-half of the cysts were simple and anechoic at ultrasound.
      Fifty-seven had a diameter not exceeding 5 cm. Forty-two cyst resolved in
      pregnancy without treatment. Three cysts required surgery within few days
      (torsion). One woman required laparotomy at the 37th week of gestation, due to
      torsion. When one case of termination was excluded, 78 women delivered at term
      (66 vaginally, 12 by caesarean section). Nineteen women underwent surgery after
      pregnancy. We recorded three Stage Ia borderline tumours, accounting for 3/82
      cysts (3.6%) and 3/30 persisting masses (10%). CONCLUSION: Ultrasound allows
      definition of ovarian cysts in pregnancy and this positively impacts on
      management. The incidence of cancer among persistent masses is lower than
      previously reported. Acute complications in stable cysts are extremely uncommon
      after the first trimester. An expectant management is successful in the majority
      of cases and should be considered more often. Routine removal of persistent cysts
      is not justified.

PMID- 12798476
TI  - Changes in nuchal translucency thickness in normal and abnormal karyotype
      fetuses.
AB  - OBJECTIVE: To investigate the dynamic trend of the nuchal translucency thickness
      between fetuses with normal and abnormal karyotype. DESIGN: Prospective
      observational study. SETTING: Ospedale Microcitemico, Cagliari, Italy.
      POPULATION: A cohort of 305 first trimester fetuses. METHODS: Fetuses with a
      nuchal translucency greater than or equal to the 95th centile were invited for a
      second nuchal translucency measurement. The finding of an 'increased or
      unchanged' or 'diminished' thickness was compared in fetuses with normal and
      abnormal karyotype. MAIN OUTCOME MEASURES: Nuchal translucency and karyotype.
      Median maternal age was 35 years (min 17, max 44) and median crown-rump length at
      first visit was 50 mm (min 38, max 80). A second nuchal translucency measurement
      was carried out in 292 fetuses, resulting in increased or unchanged values in 95
      cases and decreased nuchal translucency in 197 cases. Two hundred and twenty-six
      (77.4%) fetuses had normal karyotype and 66 (22.6%) had abnormal karyotype (44
      trisomies 21, 10 trisomies 18, 5 trisomies 13, 4 cases of 45 X0, 1 case of
      47,XXY, 1 case of 47,XXX and 1 translocation). In the 66 chromosomally abnormal
      fetuses, the second nuchal translucency measurement was enlarged or unchanged in
      37 (56%), and diminished in 29 (44%), while in the 226 normal fetuses the second
      nuchal translucency measurement was enlarged or unchanged in 58 cases (25%) and
      diminished in 168 (75%) (relative risk 2.6, 95% confidence interval 1.7-4.0).
      CONCLUSION: In fetuses with abnormal karyotype, the second nuchal translucency
      measurement tends to be increased or unchanged, while in normal cases the size of
      nuchal translucency is generally reduced.

PMID- 12798477
TI  - The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin
      receptor binding in human myometrial membranes.
AB  - OBJECTIVE: To determine the effect of the progesterone metabolite 5 beta
      dihydroprogesterone on human oxytocin receptor binding in myometrial membranes
      and on whole-cell calcium current in single myometrial cells. DESIGN: Receptor
      binding studies in human myometrial membranes prepared from biopsies taken before
      or after the onset of labour and in Chinese hamster ovary cells expressing the
      human oxytocin receptor. Whole cell patch-clamp experiments were undertaken on
      isolated myometrial cells. SETTING: University research laboratories and
      University hospital.Patients undergoing caesarean section at term either prior to
      or following onset of labour. METHODS: Myometrial biopsies were taken from women
      undergoing caesarean section. The binding affinities of oxytocin, 5 beta
      dihydroprogesterone and atosiban were determined in myometrial membranes and
      Chinese hamster ovary cells expressing the human oxytocin receptor. The effect of
      5 beta-dihydroprogesterone on inward current was also determined in isolated
      myometrial cells. Receptor binding affinity and electrophysiological inward
      current. RESULTS: 5 beta-Dihydroprogesterone did not reduce oxytocin receptor
      binding in myometrial membranes or Chinese hamster ovary cells expressing the
      human oxytocin receptor. Nor did it influence calcium current under whole-cell
      patch conditions in single myometrial cells. In contrast, atosiban inhibited
      binding in myometrial membranes prepared from samples taken either prior to or
      following labour (K(i) = 112 and 108 nM, respectively). The affinity of atosiban
      for the oxytocin receptor was much lower than oxytocin (K(i) = 5 and 6 nM in
      samples taken before or after labour, respectively) in myometrial membranes and
      in Chinese hamster ovary cells expressing the human oxytocin receptor (K(i) = 63
      M and 1 nM for atosiban and oxytocin, respectively). CONCLUSIONS: We conclude
      that 5 beta-dihydroprogesterone is unlikely to regulate myometrial activity as a
      result of a direct effect on oxytocin receptor binding or inward calcium current.

PMID- 12798479
TI  - Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial
      invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery.
AB  - OBJECTIVE: To evaluate the relationship between interleukin (IL)-18 in cervical
      mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm
      delivery and intra-amniotic inflammation in women in preterm labour, with preterm
      prelabour rupture of membranes and at term. DESIGN: A prospective follow up
      study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden. SAMPLE: Women
      with singleton pregnancies (<34 weeks) presenting with preterm labour (n = 87) or
      preterm prelabour rupture of membranes (n = 47) and women, not in labour, at term
      (n = 28). METHODS: Amniotic fluid was retrieved transabdominally. Cervical mucus
      was taken from the uterine cervix of women in preterm labour and at term. IL-18
      was analysed with enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: IL-18
      in relation to microbial invasion of the amniotic fluid, delivery within seven
      days or <34 weeks of gestation and intra-amniotic inflammation. RESULTS: The
      levels of IL-18 in cervical mucus and amniotic fluid were higher in women with
      preterm labour than in those not in labour at term. In the preterm labour group,
      significant associations were found between elevated IL-18 in amniotic fluid and
      microbial invasion of the amniotic fluid, as well as between delivery within
      seven days or <34 weeks of gestation and intra-amniotic inflammation. Delivery
      was delayed longer in the preterm prelabour rupture of membranes subgroup with IL
      18 >or=1.0 ng/mL than in that with IL-18 <1.0 ng/mL. CONCLUSIONS: In the preterm
      labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated
      with microbial invasion of the amniotic fluid, intra-amniotic inflammation and
      prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture
      of the membranes group correlated with a longer interval to delivery.

PMID- 12798478
TI  - The Doppler assessment in multiple pregnancy randomised controlled trial of
      ultrasound biometry versus umbilical artery Doppler ultrasound and biometry in
      twin pregnancy.
AB  - OBJECTIVE: To assess the addition value of umbilical artery Doppler ultrasound
      added to standard ultrasound biometry measurements in the management of twin
      pregnancies. DESIGN: A prospective randomised controlled multicentre trial of
      women with twin pregnancies. SETTING: Tertiary level referral hospitals in
      Australia, New Zealand and Southeast Asia. POPULATION: Pregnant women with twin
      pregnancies. METHODS: Women were randomised at 25 weeks of gestation to receive
      either standard ultrasound biometric assessment or standard assessment plus
      Doppler ultrasound umbilical artery flow velocity waveform analysis. The studies
      were repeated at 30 and 35 weeks unless otherwise indicated. Physicians were
      advised to institute close fetal surveillance in the presence of an abnormal
      umbilical artery Doppler study or with biometry indicators of fetal compromise.
      MAIN OUTCOME MEASURES: Standard obstetric (mode of delivery, perinatal mortality,
      hypertension, antenatal admissions and gestation at delivery) and neonatal (5
      minute Apgar scores <5, admissions to neonatal nursery and requirements for
      ventilation) outcomes and statistical analysis was on intention-to-treat. There
      were no significant differences between the two groups with respect to
      demography, antenatal, peripartum and neonatal outcomes. There was no difference
      in the perinatal mortality rate in the no Doppler group (n = 264), which was
      11/1000 live births, and the Doppler group (n = 262), which was 9/1000 live
      births. There were three unexplained intrauterine deaths in the no Doppler group
      and none in the Doppler group (OR 0.14, 95% CI 0.01-1.31). Two intrauterine
      deaths in the Doppler group were due to cord prolapse in labour and a
      fetomaternal haemorrhage, both very unlikely to be influenced by Doppler
      surveillance. CONCLUSIONS: In this study, close surveillance in twin pregnancy
      resulted in a lower than expected fetal mortality from 25 weeks of gestation in
      both the no Doppler and Doppler groups. The lower rate of unexplained fetal death
      in the no Doppler group was not significantly different from the Doppler group.

PMID- 12798480
TI  - Term breech presentation in The Netherlands from 1995 to 1999: mortality and
      morbidity in relation to the mode of delivery of 33824 infants.
AB  - OBJECTIVE: To analyse neonatal mortality and morbidity in term infants born in
      breech presentation in relation to the mode of delivery (planned caesarean
      section, emergency caesarean section or vaginal delivery) and to compare these
      findings with those of the Term Breech Trial Collaborative Group [Hannah et al.
      Lancet 2000; October]. DESIGN: Retrospective observational study. SETTING: The
      Netherlands. POPULATION: Infants (n = 33824) born at term in breech presentation
      in the Netherlands between 1995 and 1999. Multiple pregnancies, antenatal death
      and major congenital malformations were excluded. METHODS: Data derived from the
      Dutch Perinatal Database were used to compare neonatal outcome of infants born in
      breech presentation in relation to the different modes of delivery (i.e. planned
      caesarean section, emergency caesarean section and vaginal delivery). Correction
      was made for differences in parity, duration of gestation and birthweight, using
      logistic regression. MAIN OUTCOME MEASURES: Intrapartum and first-week neonatal
      death, 5 minute Apgar score and birth trauma. Vaginal delivery and emergency
      caesarean section resulted in a sevenfold increase in low Apgar score, a
      threefold increase in birth trauma and a twofold increase in perinatal mortality
      when compared with the results of planned caesarean section. CONCLUSIONS: This
      study confirms the data found by Hannah et al. on an increase in early neonatal
      morbidity and mortality, following a trial of labour in cases of term breech
      presentation. These data require carefully weighed consideration against
      increased maternal (long term) risks due to a rise in caesarean sections.

PMID- 12798481
TI  - Cohort study of operative delivery in the second stage of labour and standard of
      obstetric care.
AB  - OBJECTIVE: To assess the maternal and neonatal morbidity following operative
      delivery in the second stage of labour in relation to the standard of obstetric
      care. DESIGN: Cohort study. SETTING: Maternity units in two teaching hospitals in
      Bristol, United Kingdom. Three hundred and ninety-three women with term,
      singleton, cephalic pregnancies who required operative delivery in theatre at
      full dilatation between February 1999 and February 2000. METHODS: Morbidity was
      compared for completed instrumental delivery, failed instrumental delivery and
      immediate caesarean section in relation to duration of second stage of labour,
      number of pulls at attempted instrumental delivery, number of instruments used
      and operator experience. MAIN OUTCOME MEASURES: Maternal trauma, admission to
      special care baby unit, neonatal trauma. RESULTS: Failed instrumental delivery
      after a long second stage of labour was associated with increased maternal trauma
      (adjusted odds ratios [OR] 4.1, 95% confidence interval [CI] 1.1, 16.5). More
      than three pulls at attempted instrumental delivery was associated with increased
      neonatal trauma for completed (adjusted OR 4.2, 95% CI 1.6, 9.5) and failed
      deliveries (adjusted OR 7.2, 95% CI 2.1, 24.0). Babies delivered after failed
      instrumental delivery with more than three pulls were at increased risk of
      admission to special care baby unit (adjusted OR 6.2, 95% CI 1.6, 22.8) The use
      of multiple instruments was associated with increased neonatal trauma (adjusted
      OR 3.1, 95% CI 1.5, 6.8; adjusted OR 4.4, 95% CI 1.3, 14.4, for completed and
      failed deliveries, respectively). Excessive pulls and multiple instrument use
      were associated with an initial attempt at vaginal delivery by an inexperienced
      operator, 25/48 (52%) and 34/75 (45%). CONCLUSIONS: Guidelines for safe operative
      delivery in the second stage of labour should be developed and adhered to in
      order to reduce morbidity, particularly neonatal trauma.

PMID- 12798482
TI  - Avoidable stillbirths and neonatal deaths in rural Tanzania.
AB  - OBJECTIVE: To determine the causes of stillbirths and neonatal deaths in the
      community in rural Tanzania and to evaluate whether the deaths were avoidable
      under the prevailing circumstances. DESIGN: Review of stillbirths and neonatal
      deaths. SETTING: Rural northern Tanzania, Mbulu and Hanang districts. SAMPLE: One
      hundred and nineteen stillbirth and neonatal deaths identified in a prospective
      cohort of antenatal attendees and 21 stillbirths and neonatal deaths identified
      retrospectively in a household survey in seven rural communities. METHODS: Verbal
      autopsy was done to reach a diagnosis, in many cases supplemented with
      information from antenatal records and hospital records. The avoidability of
      deaths under the prevailing circumstances was assessed for each case. An account
      of risk factors detectable at antenatal clinic was done and compared with the
      woman's recall of the risk assessment and recall of being referred. MAIN OUTCOME
      MEASURES: Avoidability of stillbirths and neonatal deaths. RESULTS: There were 60
      stillbirths, 49 early neonatal deaths and 27 late neonatal deaths. Infection
      related deaths were most common (n = 53), followed by asphyxia-related deaths (n
      = 32) and immaturity-related deaths (n = 20). Malaria was the most common
      infectious agent observed (21 children and 20 mothers). Twenty-one deaths (15%)
      were probably avoidable and 13 (10%) were possibly avoidable. A patient-oriented
      avoidable factor was identified in 17 (51%) and a provider-oriented avoidable
      factor was identified in 22 cases (65%). Twenty-six of the 34 avoidable deaths
      had risk factors, but only two of the women were aware of it and only one
      recalled being referred to a hospital for the risk factor. There were eight
      deaths among the 133 mothers who experienced a perinatal death. CONCLUSION: Our
      data indicate that prevention and adequate treatment of infections and asphyxia
      in the newborn should have high priority in low-income settings. The relatively
      low proportion of avoidable stillbirths and neonatal deaths may be partly due to
      accessible emergency obstetric care in the area. Future efforts should emphasise
      improving the communication between midwife and women at the antenatal clinics,
      preparing the women-and their families-for the delivery and to be ready for
      complications.

PMID- 12798483
TI  - No recurrence of mature ovarian teratomas after laparoscopic cystectomy.
AB  - Recurrence of ovarian teratomas was evaluated in a randomised trial to determine
      whether laparoscopic cystectomy had the same efficacy as laparotomy. Forty
      premenopausal non-pregnant women with a unilateral teratoma no larger than 10 cm
      were randomised to laparoscopy or laparotomy. Post-operative pain, duration of
      stay in hospital and duration of convalescence were compared. Women were reviewed
      every six months for five years. A higher proportion had milder pain, faster
      hospital discharge and faster recovery following laparoscopy than laparotomy.
      There were no recurrences of teratomas in both arms of the study, suggesting that
      laparoscopy has the same efficacy as laparotomy.

PMID- 12798484
TI  - A case of villoglandular papillary adenocarcinoma of the cervix with lymph node
      metastasis.

PMID- 12798485
TI  - Symphyseal diastasis and vestibular rupture during spontaneous vaginal delivery.

PMID- 12798486
TI  - Thyroid hormone resistance and pregnancy.

PMID- 12798487
TI  - Pregnancy complicated by Werner's syndrome.

PMID- 12798488
TI  - Endometriotic cyst after subtotal abdominal hysterectomy mimicking carcinoma of
      the cervical stump.

PMID- 12798490
TI  - Sex steroid hormones do not influence the oxidative burst activity of
      polymorphonuclear leukocytes from ovariectomized cows in vitro.
AB  - During the periparturient period, dairy cows are subjected to physiological
      changes that may induce immunosuppression and an increased susceptibility of the
      animal to bacterial infections such as mastitis. The incidence of clinical
      environmental mastitis is high during the last period of gestation, at
      parturition and during the first month of lactation, suggesting a potential
      influence of sex steroid hormones. Efficient functioning of polymorphonuclear
      leukocytes (PMN) is necessary during the early phase of infection to clear the
      mammary gland from invading pathogens. The purpose of this study was to
      investigate the effect of sex steroid hormones on the oxidative burst activity of
      isolated PMN from ovariectomized cows. Ovariectomy was performed to minimize the
      interference of endogenous estrogen and progesterone levels, which are known to
      vary extensively during the estrus cycle. Isolated PMN were incubated with
      different concentrations of 17beta-estradiol, estrone or progesterone. A flow
      cytometric technique was used to quantify the oxidation of intracellular 2',7'
      dichlorofluorescin by the oxidative burst system of PMN following stimulation
      with phorbol myristate acetate. Staurosporine was used as a positive control for
      our in vitro model. No statistically significant changes in PMN oxidative burst
      activity were observed at physiological or pharmacological levels of the three
      sex steroid hormones. A large variation existed in the oxidative burst activity
      among cows. In an additional experiment, the expression of estrogen receptor
      alpha and of progesterone receptor in PMN was evaluated immunohistochemically. No
      specific staining was detected for both receptors in isolated PMN following
      incubation with different concentrations of sex steroid hormones.

PMID- 12798491
TI  - Optimization of the allylic oxidation in the synthesis of 7-keto-delta5-steroidal
      substrates.
AB  - A variety of delta5-steroids were converted into alpha, beta-unsaturated 7
      ketones using a modification of the already known method of t-butyl hydroperoxide
      in the presence of copper iodide in acetonitrile. The same alteration was applied
      to another oxidative procedure, which had never been used before on steroidal
      substrates. The same oxidative agent was used in the presence of copper iodide,
      and tetra-n-butylammonium bromide was used as a phase-transfer catalyst in a two
      phase system of water/methylene chloride. It was found that the allylic oxidation
      proceeded more efficiently when t-butyl hydroperoxide was added to the reaction
      mixture in portions. The initial addition of the total amount of oxidant or its
      dropwise addition afforded low yields. This observation contributes to the
      investigation of the reaction mechanism, and high-yield conversions of steroidal
      5,6-enes into the corresponding conjugated 7-ones in short reaction times are
      reported.

PMID- 12798492
TI  - Microbial conversion of pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione acetates
      by Nocardioides simplex VKM Ac-2033D.
AB  - The conversion of pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione 21-acetate (I)
      and 17,21-diacetate (VI) by Nocardioides simplex VKM Ac-2033D was studied. The
      major metabolites formed from I were identified as pregna-1,4,9(11)-triene
      17alpha,21-diol-3,20-dione 21-acetate (II) and pregna-1,4,9(11)-triene-17alpha,21
      diol-3,20-dione (IV). Pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione (III) and
      pregna-1,4,9(11)-triene-17alpha,20beta,21-triol-3-one (V) were formed in
      minorities. Biotransformation products formed from VI were pregna-1,4,9(11)
      triene-17alpha,21-diol-3,20-dione 17,21-diacetate (VII), pregna-1,4,9(11)-triene
      17alpha,21-diol-3,20-dione 21-acetate (II), pregna-1,4,9(11)-triene-17alpha,21
      diol-3,20-dione (IV), pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 17
      acetate (VIII), pregna-1,4,9(11)-triene-17alpha,20beta,21-triol-3-one (V). The
      conversion pathways were proposed including 1(2)-dehydrogenation, deacetylation,
      20beta-reduction and non-enzymatic migration of acyl group from position 17 to
      21. The conditions providing predominant accumulation of pregna-1,4,9(11)-triene
      17alpha,21-diol-3,20-dione 21-acetate (II) from I and pregna-1,4,9(11)-triene
      17alpha,21-diol-3,20-dione 17-acetate (VIII) from VI in a short-term
      biotransformation were determined.

PMID- 12798493
TI  - 1alpha,25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC
      beta activity via phospholipase A2-dependent production of lysophospholipid.
AB  - 1alpha,25(OH)(2)D(3) activates protein kinase C (PKC) in rat growth plate
      chondrocytes via mechanisms involving phosphatidylinositol-specific phospholipase
      C (PI-PLC) and phospholipase A(2) (PLA(2)). The purpose of this study was to
      determine if 1alpha,25(OH)(2)D(3) activates PI-PLC directly or through a PLA(2)
      dependent mechanism. We determined which PLC isoforms are present in the growth
      plate chondrocytes, and determined which isoform(s) of PLC is(are) regulated by
      1alpha,25(OH)(2)D(3). Inhibitors and activators of PLA(2) were used to assess the
      inter-relationship between these two phospholipid-signaling pathways. PI-PLC
      activity in lysates of prehypertrophic and upper hypertrophic zone (growth zone)
      cells that were incubated with 1alpha,25(OH)(2)D(3), was increased within 30s
      with peak activity at 1-3 min. PI-PLC activity in resting zone cells was
      unaffected by 1alpha,25(OH)(2)D(3). 1beta,25(OH)(2)D(3), 24R,25(OH)(2)D(3),
      actinomycin D and cycloheximide had no effect on PLC in lysates of growth zone
      cells. Thus, 1alpha,25(OH)(2)D(3) regulation of PI-PLC enzyme activity is
      stereospecific, cell maturation-dependent, and nongenomic. PLA(2)-activation
      (mastoparan or melittin) increased PI-PLC activity to the same extent as
      1alpha,25(OH)(2)D(3); PLA(2)-inhibition (quinacrine,
      oleyloxyethylphosphorylcholine (OEPC), or AACOCF(3)) reduced the effect of
      1alpha,25(OH)(2)D(3). Neither arachidonic acid (AA) nor its metabolites affected
      PI-PLC. In contrast, lysophosphatidylcholine (LPC) and
      lysophosphatidylethanolamine (LPE) activated PI-PLC (LPE>LPC).
      1alpha,25(OH)(2)D(3) stimulated PI-PLC and PKC activities via Gq; GDPbetaS
      inhibited activity, but pertussis toxin did not. RT-PCR showed that the cells
      express PLC-beta1a, PLC-beta1b, PLC-beta3 and PLC-gamma1 mRNA. Antibodies to PLC
      beta1 and PLC-beta3 blocked the 1alpha,25(OH)(2)D(3) effect; antibodies to PLC
      delta and PLC-gamma did not. Thus, 1alpha,25(OH)(2)D(3) regulates PLC-beta
      through PLA(2)-dependent production of lysophospholipid.

PMID- 12798495
TI  - A new ecdysteroid, 2-deoxy-5beta,20-dihydroxyecdysone from the fruits of
      Diploclisia glaucescens.
AB  - Chemical investigation of ethyl acetate extract of the fruits of Diploclisia
      glaucescens of the family Menispermaceae furnished a new ecdysteroid 2-deoxy
      5beta,20-dihydroxyecdysone, together with 20-hydroxyecdysone, 3-deoxy-1beta,20
      dihydroxyecdysone, 2-deoxy-20-hydroxyecdysone, 24-ethyl-20-hydroxyecdysone
      (makisterone C). Latter two ecdysteroids are reported first time from the family
      Menispermaceae.

PMID- 12798494
TI  - Sex-differences in adrenocortical responsiveness during development in rats.
AB  - It is known that the stress hyporesponsive period (SHRP), which seems to be
      related to an immature hypothalamo-pituitary-adrenal (HPA) regulatory system,
      occurs during the first 2 weeks after birth in rats. In the present study, we
      investigated the effects of sex-steroid hormones on adrenocortical responsiveness
      to adrenocorticotropic hormone (ACTH) in neonatal rats. The levels of cyclic
      adenosine 3',5'-monophosphate (cAMP), corticosterone, and adenylate cyclase
      activity increased with the dose of ACTH in adrenal cells of males and females in
      vitro. The ACTH responsiveness in adrenal cells increased with age (7-35 days of
      age), that is, the loss in responsiveness to ACTH just after birth began to
      recover in 14-35-day-old rats, but the responsiveness in 14-day-old rats was
      attenuated in males compared with females. Although castration markedly augmented
      the responsiveness in male rats, testosterone-replacement in the castrated male
      rats inhibited the enhancement. Furthermore, the responsiveness in 14-day-intact
      female rats was suppressed by treatment with testosterone. Expression levels of
      ACTH receptor mRNA in adrenals increased with age in the female rat, but not in
      the male. Castration enhanced the level of ACTH receptor mRNA to three-fold of
      that in intact male rats at 14 days of age, but replacement treatment with
      testosterone in castrated male rats lowered the elevated levels. Testicular
      androgens are thought to evoke a gender-specific response in neonates, and the
      temporal decrease of adrenal ACTH-responsiveness might be due to the topically
      immature adrenal system as well as the central nervous system in mammals.

PMID- 12798496
TI  - Stereoselective halogenation of the 16-hydroxymethyl-3-methoxy-13alpha-estra
      1,3,5(10)-trien-17-ols and their solvolytic investigation.
AB  - The primary hydroxy functions of 16alpha-hydroxymethyl-3-methoxy-13alpha-estra
      1,3,5(10)-trien-17beta-ol (3a) and 16beta-hydroxymethyl-3-methoxy-13alpha-estra
      1,3,5(10)-trien-17alpha-ol (4a) were stereoselectively transformed into good
      leaving groups. On alkaline methanolysis of the 16-halomethyl or 16
      tolylsulfonyloxymethyl derivatives, a new D-seco-13alpha-estrone derivative was
      obtained in high yield.

PMID- 12798497
TI  - First synthesis of phosphonobile acids and preliminary studies on their
      aggregation properties.
AB  - The synthesis of three novel phosphonobile acids from natural bile acids is
      reported. The CMC of phosphonodeoxycholic acid (PDCA) at pH 8.2 was found to be
      lower than that of the parent deoxycholic acid (DCA). PDCA micelles were also
      found to have higher microviscosity compared to DCA micelles, suggesting higher
      hydrophobicity and tighter packing in the interior of PDCA micelles. PDCA
      aggregated further to form an aqueous gel at pH 4.

PMID- 12798498
TI  - Hormonal monitoring of ovarian activity using the Ovarian Monitor, part I.
      Validation of home and laboratory results obtained during ovulatory cycles by
      comparison with radioimmunoassay.
AB  - A study was conducted to determine the accuracy and reliability of the Home
      Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol
      glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian
      activity. Approximately 60 ovulating women in three centres collected timed
      specimens of urine (3h or more) for a total of six cycles each. The women
      measured the E1G and PdG excretion per 24h in their urine specimens using the
      Monitor. A local laboratory using the Monitor also measured the excretion. Urine
      specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory
      in London where they were analysed for E1G and PdG by the Monitor and by
      radioimmunoassay (RIA). The correlation coefficients between the Monitor and
      radioimmunoassay results obtained in London were better than 0.84 in 80% of the
      cycles. A urine bias caused the Monitor E1G results to be higher than those
      obtained by radioimmunoassay but the daily patterns were the same. In 50% of the
      cycles, this bias caused a delay of up to 3 days in identifying the beginning of
      the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak
      and the postovulatory PdG rise agreed within the experimental errors of the two
      systems. The study confirmed that women using the Monitor at home obtained
      results that were as accurate as those obtained by laboratory procedures. Careful
      supervision was required to maintain laboratory levels of quality control and
      interpretation of results.

PMID- 12798499
TI  - Secretion of 6beta-hydroxycortisol by normal human adrenals and adrenocortical
      adenomas.
AB  - Although 6beta-hydroxycortisol (6betaOHF) is usually considered a cortisol
      metabolite produced by the liver, a few reports suggest that it may also
      originate from extrahepatic sources. To examine whether human adrenal cells are
      capable of 6beta-hydroxylating cortisol, we measured 6betaOHF secretion with a
      radioimmunoassay method in isolated human adrenal cell systems obtained from
      three normal adrenals, four nonhyperfunctioning adrenocortical adenomas, two
      adrenal adenomas causing Cushing's syndrome, and five aldosterone (Aldo)
      producing adenomas. Cells were examined both under basal conditions and after
      stimulation with adrenocorticotrophic hormone (ACTH). In addition, 6betaOHF
      concentrations were determined in inferior vena cava and suprarenal vein plasma
      samples obtained from the side of nonhyperfunctioning adrenal adenomas (five
      patients) and aldosterone-producing adenomas (five patients). Under basal
      incubation conditions, 6betaOHF secretion, expressed as a percent of cortisol
      secretion, was between 0.5 and 2.0% in normal adrenal cells, between 1.0 and 7%
      in cells from nonhyperfunctioning adenomas, 12 and 15% in cells from Cushing's
      syndrome patients, and between 2.6 and 3.9% in cells from aldosterone-producing
      adenomas. In these cells, increasing doses of ACTH produced a dose-dependent
      stimulation of both 6betaOHF and cortisol secretion. The 6betaOHF concentration
      in suprarenal vein samples obtained from the side of adenomas was markedly
      increased; the suprarenal vein/inferior vena cava 6betaOHF ratios were 13.1+/-2.1
      (mean+/-S.E.) in the case of nonhyperfunctioning adenomas and 17.8+/-4.5 in the
      case of aldosterone-producing adenomas. These results firmly suggest that
      6betaOHF is not only a hepatic metabolite, but also a secretory product of human
      adrenals and that similarly to cortisol, its secretion may be controlled by ACTH.

PMID- 12798501
TI  - Organization of satellite DNA in the genome of Trypanosoma cruzi.
AB  - Trypanosoma cruzi has about 10(5) copies of a 195 bp repeat, called satellite
      DNA, which correspond to about 10% of the total DNA. Since very little is known
      about satellite distribution and function in this and in many other organisms, we
      studied the genomic organization of satellite DNA in T. cruzi Y, CL Brener, and
      Silvio X10 cl1 strains. We found that satellite repeats are present in some, but
      not all, chromosomes in these strains. We also found that the copy number of the
      satellite repeats is distinct in each one of the strains. We have estimated that
      the satellite DNA is four to six times more abundant in Y and CL Brener strains
      as compared to Silvio X10 cl1. Despite these differences, the repeated units are
      organized in a similar way. Based on restriction nuclease digestion analysis, we
      found that satellite repeats are grouped in clusters comprising about 30+/-10 kb.
      The same cluster size was also found in the different chromosomes, as seen by two
      dimensional pulsed field-gel electrophoresis. As evidenced by a fluorescence
      hybridization assay of spread DNA fibers, we additionally found that these
      clusters are constrained in specific regions of the chromosomes. Sequence
      analysis of several repeat units of satellite DNA of the three strains revealed a
      remarkable similarity with conserved nucleotide blocks separated by more variable
      regions. Such conserved distribution and common sequence may suggest that these
      repeated units might have a structural role in the T. cruzi chromosomes.

PMID- 12798502
TI  - Efficiency and specificity of RNA interference generated by intra- and
      intermolecular double stranded RNA in Trypanosoma brucei.
AB  - In many eukaryotes, double-stranded (ds) RNA leads to specific degradation of RNA
      of cognate sequence, a process termed RNA interference (RNAi). Here we used the
      protozoan Trypanosoma brucei as a model to investigate efficiency and specificity
      of RNAi generated by expression of long dsRNA of PFRA and PFRC genes, which code
      for flagellar proteins required for cell motility. Consequences of RNAi were
      monitored at all three levels: target RNA expression, protein expression and
      phenotype observation, using population or individual cell analysis. Expression
      of PFRA dsRNA from an inverted repeat was extremely efficient, knocking down PFRA
      RNA and PFRA protein, and producing a severe paralysis phenotype. Silencing by
      expression of PFRA dsRNA using a dual facing promoter system was also very
      efficient, producing a clear phenotype, although low amounts of PFRA RNA and PFRA
      protein were detected. Expression via the dual facing promoters of PAR2 dsRNA
      (83% overall identity with PFRA, including nine blocks of >20 nt total identity)
      did not produce significant reduction of total amounts of PFRA RNA or PFRA
      protein. However, individual cell analysis by immunofluorescence revealed that 10
      60% cells (depending on subclones) exhibited lower PFRA amounts in their
      flagellum, producing a reduced-motility phenotype.

PMID- 12798504
TI  - Expression, localization and alternative function of cytoplasmic asparaginyl-tRNA
      synthetase in Brugia malayi.
AB  - Aminoacyl-tRNA synthetases (AARS) are a family of enzymes that exhibit primary
      and various secondary functions in different species. In Brugia malayi, the gene
      for asparaginyl-tRNA synthetase (AsnRS), a class II AARS, previously has been
      identified as a multicopy gene encoding an immunodominant antigen in the serum of
      humans with lymphatic filariasis. However, the relative level of expression and
      alternative functions of AARS in nematode parasites is not well understood. We
      searched the Filarial Genome Project database to identify the number and amino
      acid specificity of B. malayi AARS cDNAs to gain insight into the role of
      different AARS in filaria. These data showed that cytoplasmic AsnRS was present
      in five gene clusters, and is the most frequently represented member of the
      aminoacyl-tRNA synthetase family in adult B. malayi. The relative level of AsnRS
      transcribed in adult female B. malayi was compared to the levels of a low
      abundance and medium abundance AARS by quantitative real-time RT-PCR. By this
      method, AsnRS cDNA was 11 times greater than arginyl-tRNA synthetase and
      methionyl-tRNA synthetase cDNA. In situ hybridization using a B. malayi AsnRS
      specific oligonucleotide probe identified abundant cytoplasmic mRNA, particularly
      in the hypodermis of adult B. malayi. In the absence of tRNA, AsnRS synthesizes
      diadenosine triphosphate, a potent regulator of cell growth in other eukaryotes.
      These data support the hypothesis that all AARS are not equally expressed in B.
      malayi and that these enzymes may demonstrate important alternative functions in
      filaria.

PMID- 12798506
TI  - Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR.
AB  - A real-time PCR technique that allows for accurate and sensitive quantitation of
      tissue parasite burden in animals infected with the protozoan parasite
      Trypanosoma cruzi was developed. The utility of this method was demonstrated by
      confirmation of higher parasite load in mice with acute infections in comparison
      to chronically infected mice, detection of tissue-restricted parasite persistence
      in different parasite:host strain combinations, and the observation of increased
      tissue parasite burden with higher infective doses. This method should be a
      useful tool for monitoring parasite burden in hosts under various treatment
      regimens.

PMID- 12798505
TI  - Use of RNA interference to investigate gene function in the human filarial
      nematode parasite Brugia malayi.
AB  - We describe the successful use of the reverse genetic technique RNA interference
      (RNAi) to investigate gene function in the human filarial nematode parasite
      Brugia malayi. We used fluorescently labelled double stranded RNA (dsRNA) to
      demonstrate that 300 bp molecules are able to enter adult females in culture
      while they remain excluded from microfilariae (mf). We have developed an
      optimised microvolume culture system to allow the exposure of parasites to high
      concentrations of dsRNA for extended periods. Culturing of adult female parasites
      in this system for 24h does not significantly reduce parasite lifespan or mf
      release in culture. Three B. malayi genes, beta-tubulin (Bm-tub-1), RNA
      polymerase II large subunit (Bm-ama-1) and B. malayi mf sheath protein 1/mf22 (Bm
      shp-1) were targeted by soaking adult female B. malayi in dsRNA complementary to
      these transcripts in the optimised culture system. Targeting of the two
      housekeeping genes Bm-tub-1 and Bm-ama-1 led to a reduction in the levels of
      their transcripts, as assessed by reverse transcriptase coupled PCR (RT-PCR), and
      resulted in parasite death in culture. In contrast, targeting of the Bm-shp-1
      gene was not lethal to adult females in culture. A marked reduction in mf release
      was observed for shp-1 RNAi parasites compared to controls and in addition 50% of
      mf released did not have fully elongated sheaths. This "short" phenotype
      correlated with the loss of the stockpiled shp-1 transcript from developing mf in
      treated adult female gonads. From these data we conclude that RNAi may be a
      useful method for assessment of drug target potential of genes identified in
      filarial gene discovery projects.

PMID- 12798508
TI  - The 5' end structure of transcripts derived from the rRNA gene and the RNA
      polymerase I transcribed protein coding genes in Trypanosoma brucei.
AB  - Due to trans-splicing and polycistronic transcription, the 5' end structure of
      precursor RNAs of protein coding genes in Trypanosoma brucei has not yet been
      characterized. In eukaryotes, in general, the 5' ends of transcripts generated by
      RNA polymerase (pol) I and pol II are different. Pol I derived precursor RNAs
      contain an unmodified tri- or diphosphate group at their 5' ends. In contrast,
      pol II primary transcripts, the 5' triphosphate (initially also part of the pre
      mRNA) is rapidly modified by the addition of methylated guanosine triphosphate,
      immediately after transcription initiation. We determined the 5' end structure of
      precursor RNAs of the rRNA gene and the RNA pol I transcribed protein coding gene
      by the differential display of RNA ligase mediated amplification of cDNA ends
      (DDRLACE) method. Comparing the ability of the 5' end of RNA transcripts to
      ligate with an RNA primer following different pre-treatments, the structure of
      the 5' end of RNA transcripts was characterized. We found that: (1). the 5' end
      of putative precursor RNAs from a pol I transcribed protein coding gene and the
      rRNA gene was uncapped; (2). approximately 20% of the putative rRNA precursor
      contained a 5' tri- or diphosphate group, representing the primary transcript and
      approximately 80% of the putative rRNA precursor were dephosphorylated and
      contained a 5' hydroxyl group; (3). the majority of putative neomycin resistance
      gene precursor RNAs, driven by the procyclin gene promoter (a pol I promoter),
      contained a 5' hydroxyl group. The procyclin-neo primary transcript, as being
      those containing a 5' tri- or diphosphate, was below a detectable level in the
      steady state RNA; and (4). we did not detect pol I transcribed precursor RNAs
      that contained a 5' monophosphate group. The observation that the putative pre
      RNAs derived from the procyclin gene promoter, similar to those of rRNA do not
      have a 5' capped structure, is consistent with the notion that transcription of
      pol I transcribed protein coding genes is crucially dependent on trans-splicing
      for the cap addition.

PMID- 12798509
TI  - Evaluation of Trypanosoma cruzi hybrid stocks based on chromosomal size
      variation.
AB  - Although all classical lines of evidence point to the fact that Trypanosoma cruzi
      has a predominantly clonal evolution, accumulating data show that some T. cruzi
      stocks are the result of hybridisation events. We evaluated whether chromosomal
      polymorphism would give evolutionary information on hybrid isolates. Twenty-three
      coding sequences were mapped on the chromosomes of nine parasite stocks, four of
      which are putative hybrids (CL Brener and rDNA group 1/2). Phenetic analyses of
      karyotype data were based on the absolute chromosomal size difference index
      (aCSDI), a method that assumes that the genomic distance between two organisms is
      the sum of the size differences between their homologous chromosomes. aCSDI-based
      dendrograms obtained from a variable number of probes (3-18 probes) defined in
      all the cases three clusters: two corresponding, respectively, to T. cruzi I and
      T. cruzi II groups; and a third one, to rDNA group 1/2. CL Brener was
      alternatively positioned in T. cruzi II or rDNA group 1/2 clusters. Three
      clusters were also observed in the dendrogram constructed with restriction
      fragment length polymorphism (RFLP) data from 18 probes. The topology of the
      chromosome and RFLP dendrograms is similar, with a significant correlation
      coefficient (r=0.86062; P<0.0001), supporting a strong structuring of the
      clusters. This study also revealed that hybrid stocks have a larger proportion of
      two different-sized homologous chromosomes, as compared with non-hybrid strains.
      Overall, our results show that chromosomes are valuable characters for
      identification of evolutionary groups, in particular, T. cruzi hybrid organisms.

PMID- 12798507
TI  - Angiogenic activity of an Onchocerca volvulus Ancylostoma secreted protein
      homologue.
AB  - Angiogenesis is an important step in the development of ocular onchocercaisis. In
      previous studies, it has been demonstrated that Onchocerca volvulus homologues of
      the Ancylostoma secreted protein family have pronounced angiogenic activity. The
      overall goal of the current study was to determine if this angiogenic effect is
      exerted through a direct or indirect mechanism. These studies focused on one
      member of this family, OvASP-2, as this protein is expressed in microfilaria, the
      stage of the parasite that causes ocular onchocercaisis. Clones encoding
      truncated and full length open reading frames were expressed as fusion proteins
      with Escherichia coli maltose binding protein (MBP), and angiogenic activity was
      compared in vitro and in vivo with MBP alone. Truncated constructs expressing
      only the first 105 amino acids of OvASP-2 were as active as the full length
      protein in inducing new blood vessel formation. The full length fusion protein
      did not stimulate proliferation or production of vascular endothelial growth
      factor in vascular endothelial cells in vitro, indicating that OvASP-2 does not
      directly stimulate angiogenesis. Sequence analysis demonstrated that the gene
      encoding OvASP-2 contained five introns. Sequence comparisons of the genomic loci
      from West African blinding and non-blinding strains of O. volvulus revealed that
      some polymorphism existed among the various isolates tested. However, none of
      these polymorphisms could be used to differentiate the parasite strains,
      suggesting that qualitative variation in OvASP-2 could not explain the difference
      in ocular pathogenic potential of the two parasite strains.

PMID- 12798510
TI  - New tools to identify var sequence tags and clone full-length genes using type
      specific primers to Duffy binding-like domains.
AB  - Cytoadherence of infected erythrocytes is a hallmark of Plasmodium falciparum
      infection and a key determinant in the particular virulence of this species.
      Infected erythrocytes bind a variety of host receptors but certain adhesion
      traits are associated with more severe disease. A large, diverse protein family
      named P. falciparum erythrocyte membrane protein 1 (PfEMP1) is responsible for
      sequestration of mature stage infected erythrocytes and orchestrates parasite
      binding tropism. To better understand the molecular basis for malaria disease,
      more study is needed to identify the subset of PfEMP1 variants that contribute to
      basic disease phenotypes. PfEMP1 proteins have multiple receptor-like domains
      that group into different homology types based upon sequence similarity.
      Universal primers have been developed that recognize some, but not all PfEMP1
      adhesion domain types. In this study, we designed and validated a new series of
      type-discriminatory primers to the DBL-beta, -gamma, and -delta adhesion types
      for epidemiological profiling. In addition, we used new primers to the var
      upstream region and exon 2 to demonstrate how the strategic placement of primers
      throughout the gene structure can be exploited to efficiently clone the var gene
      coding region. These new approaches provide valuable tools to gain novel insights
      into cytoadherence and malaria pathogenesis.

PMID- 12798503
TI  - Gene discovery in the Entamoeba invadens genome.
AB  - Entamoeba invadens, a parasite of reptiles, is a model for the study of
      encystation by the human enteric pathogen Entamoeba histolytica, because E.
      invadens form cysts in axenic culture. With approximately 0.5-fold sequence
      coverage of the genome, we were able to get insights into E. invadens gene and
      genome features. Overall, the E. invadens genome displays many of the features
      that are emerging from ongoing genome sequencing efforts in E. histolytica. At
      the nucleotide level the E. invadens genome has on average 60% sequence identity
      with that of E. histolytica. The presence of introns in E. invadens was predicted
      with similar consensus (GTTTGT em leader A/TAG) sequences to those identified in
      E. histolytica and Entamoeba dispar. Sequences highly repeated in the genome of
      E. histolytica (rRNAs, tRNAs, CXXC-rich proteins, and Leu-rich repeat proteins)
      were found to be highly repeated in the E. invadens genome. Numerous proteins
      homologous to those implicated in amoebic virulence, (Gal/GalNAc lectins,
      amoebapores, and cysteine proteinases) and drug resistance (p-glycoproteins) were
      identified. Homologs of proteins involved in cell cycle, vesicular trafficking
      and signal transduction were identified, which may be involved in en/excystation
      and cell growth of E. invadens. Finally, multiple copies of a number of E.
      invadens genes coding for predicted enzymes involved in core metabolism and the
      targets of anti-amoebic drugs were identified.

PMID- 12798511
TI  - Evaluation of differential gene expression in Leishmania major Friedlin
      procyclics and metacyclics using DNA microarray analysis.
AB  - The various Leishmania species are flagellated protozoans, responsible for a wide
      spectrum of human diseases. The sequence of the L. major genome is nearing
      completion and a large proportion of the identified genes have yet to be ascribed
      functions. DNA microarrays containing PCR-amplified DNA from a random amplified
      genomic library of L. major Friedlin (LmjF) [Mol. Biochem. Parasitol. 113 (2001)
      337] were hybridized with fluorescent probes made from L. major Friedlin RNA from
      five time-points during differentiation from procyclics to metacyclics. The data
      were normalized for background and probe intensity and the relative abundance of
      RNA for each spot was calculated. Almost 15% (1387/9282) of the DNAs showed
      statistically significant (P<0.01) changes in expression (1.1-5-fold) during the
      transition, with 1.16% (108) showing up-regulation at two or more time-points and
      0.14% (13) showing down-regulation. Northern blot analyses of selected genes
      confirmed these results. These studies confirmed the stage-specific expression of
      several known genes, as well as identifying a number of novel genes that are up
      regulated in either procyclics or metacyclics.

PMID- 12798512
TI  - Haemonchus contortus: HcGluCla expressed in Xenopus oocytes forms a glutamate
      gated ion channel that is activated by ibotenate and the antiparasitic drug
      ivermectin.
AB  - Ion channels are targets for many drugs including insecticides and anthelminthic
      agents such as ivermectin (IVM) and moxidectin (MOX). IVM has been shown to
      activate glutamate-gated chloride channels (GluCls) from the free-living
      nematode, Caenorhabditis elegans. Haemonchus contortus is a parasitic nematode
      that is also extremely sensitive to IVM. The high sensitivity of H. contortus to
      IVM is probably the result of the fact that, like C. elegans, H. contortus also
      express GluCls. To investigate the potential physiological response to IVM in H.
      contortus we have expressed a GluCl from this parasite (H. contortus glutamate
      gated chloride channel, HcGluCla) in Xenopus oocytes. HcGluCla expressed in
      oocytes formed a homomeric channel that responded to glutamate and ibotenate as
      well as the anthelmintics IVM and MOX. The response to glutamate and ibotenate
      was fast acting and reversible whereas the response to IVM and MOX was a slower
      activating channel that was essentially irreversible. These results suggest that
      IVM toxicity in H. contortus is the result of its irreversible activation of
      GluCls.

PMID- 12798513
TI  - Plasmodium falciparum falcilysin: an unprocessed food vacuole enzyme.

PMID- 12798514
TI  - Recent developments in preventing recurrent preterm birth.

PMID- 12798515
TI  - Recombinant activated factor VII: a new weapon in the fight against hemorrhage.

PMID- 12798517
TI  - Potter EL bilateral absence of ureters and kidneys: a report of 50 cases. Obstet
      Gynecol 1965;25:3-12.

PMID- 12798518
TI  - Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized
      controlled trial.
AB  - OBJECTIVE: Emergency contraceptives can prevent unintended pregnancy after
      unprotected intercourse. The best-studied regimen ("Yuzpe") consists of ordinary
      combined oral contraceptives containing levonorgestrel and ethinyl estradiol.
      Women traditionally take one dose within 72 hours after unprotected intercourse,
      and a second dose 12 hours later. Historically, half experience nausea and a
      fifth vomit. The purpose of this study was to determine whether 1). women could
      use combined oral contraceptives other than those containing levonorgestrel and
      2). eliminating the second dose improves comfort and convenience. METHODS: Women
      presenting within 72 hours after unprotected intercourse were randomized to
      receive 1). standard two-dose Yuzpe, 2). a variant of Yuzpe substituting
      norethindrone for levonorgestrel, or 3). only the first dose of Yuzpe, followed
      12 hours later by a placebo. RESULTS: Perfect-use failure rates were low in all
      groups and did not differ in a statistically significant way (standard Yuzpe 2.0%
      [n = 589], norethindrone-ethinyl estradiol 2.7% [n = 547], single dose of Yuzpe
      2.9% [n = 546]). Typical-use failure rates were slightly higher but similarly did
      not differ significantly. Side effects were similar across groups, except that
      women taking the single dose reported half the vomiting. Taking the pills with
      food did not seem to reduce nausea or vomiting, and the pills were not more
      effective when started sooner after unprotected intercourse. CONCLUSION: Oral
      contraceptives containing norethindrone-ethinyl estradiol work approximately as
      well for emergency contraception as levonorgestrel-ethinyl estradiol formulations
      and should be offered when first-line therapies are not available.

PMID- 12798519
TI  - Extending the time limit for starting the Yuzpe regimen of emergency
      contraception to 120 hours.
AB  - OBJECTIVE: Current protocols state that the Yuzpe regimen of emergency
      contraception can be initiated up to 72 hours after unprotected intercourse. The
      purpose of this study was to determine whether the window for emergency hormonal
      contraception can be extended to 120 hours. METHODS: In an observational study,
      we tracked 111 women who requested emergency contraception between 72 and 120
      hours after unprotected sex but refused postcoital copper intrauterine devices
      (IUDs), preferring instead the Yuzpe regimen. We compared failure rates for this
      group with rates among 675 otherwise similar women who started the same therapy
      within 72 hours. RESULTS: Both perfect use (1.9%) and typical use (3.6%) failure
      rates were low among women presenting between 72 and 120 hours after unprotected
      intercourse. These rates did not statistically differ from failure rates for the
      standard Yuzpe regimen (2.0% during perfect use and 2.5% during typical use). Our
      small sample size of 111, however, gave us just 25% power to detect a doubling in
      the failure rates (2% to 4%) and 59% power to detect a tripling in the failure
      rates (2% to 6%). CONCLUSION: The 72-hour cutoff for the Yuzpe regimen of
      emergency contraception appears needlessly restrictive. Women who request this
      therapy more than 72 hours after unprotected sex should be allowed to receive it,
      particularly if they decline postcoital insertion of a copper IUD and would
      otherwise have no options for reducing pregnancy risk.

PMID- 12798520
TI  - Successful treatment with recombinant factor VIIa for intractable bleeding at
      pelvic surgery.
AB  - BACKGROUND: Postoperative bleeding may be complicated by failure to identify the
      site of bleeding, multiple bleeding points, and persistent hemorrhage despite
      surgical intervention. CASE: Activated recombinant factor VII was used
      successfully in a patient with life-threatening postsurgical bleeding after
      resection of two large extraperitoneal pelvic sarcomas. CONCLUSION: In severe
      hemorrhage, hemostasis can be achieved with activated recombinant factor VII.

PMID- 12798521
TI  - Successful treatment of life-threatening postpartum hemorrhage with recombinant
      activated factor VII.
AB  - BACKGROUND: Postpartum hemorrhage is one of the most common causes of maternal
      mortality and morbidity worldwide. The aims of treatment are to maintain the
      circulation and to stop the bleeding. The latter is achieved by either medical or
      surgical management. In intractable bleeding, emergency hysterectomy is usually
      required. CASE: A 30-year-old nullipara presented with major postpartum
      hemorrhage due to uterine atony and vaginal lacerations. The patient developed
      hemorrhagic shock, resulting in prolonged prothrombin time, prolonged activated
      partial thromboplastin time, and low levels of factor VIII and fibrinogen.
      Treatments with uterotonic drugs, suturing, ligation of internal iliac arteries,
      subtotal hysterectomy, packing of the pelvis, and blood transfusion failed to
      control diffuse pelvic and vaginal bleeding. Recombinant activated factor VIIa
      (60-microg/kg intravenous bolus injection) was given as a final attempt to
      control the bleeding. The bleeding was successfully controlled within 10 minutes
      after administration. No side effects were noted. CONCLUSION: Recombinant factor
      VIIa may be an alternative hemostatic agent in a patient with life-threatening
      postpartum hemorrhage unresponsive to conventional therapy.

PMID- 12798522
TI  - Serum and follicular fluid cytokines in polycystic ovary syndrome during
      stimulated cycles.
AB  - OBJECTIVE: To investigate the serum and intrafollicular tumor necrosis factor
      alpha and interleukin-6 concentrations in infertile women with polycystic ovary
      syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS: Thirty-one
      patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating
      women matched for age and body mass index and undergoing IVF for male infertility
      were the control group. Serum tumor necrosis factor-alpha, interleukin-6, and
      estradiol levels were assayed before recombinant follicle-stimulating hormone
      stimulation under gonadotropin-releasing hormone analogue suppression and 34-36
      hours after human chorionic gonadotropin (hCG) administration at the time of the
      oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in
      the follicular fluids obtained at the time of oocyte retrieval. RESULTS: The
      patients with PCOS had higher serum and follicular fluid tumor necrosis factor
      alpha and interleukin-6 concentrations (P <.001) and lower follicular fluid
      estradiol levels (P <.05) than control women. In both groups, the serum tumor
      necrosis factor-alpha, interleukin-6, and estradiol values increased
      significantly after hCG stimulation. In both groups, the follicular fluid
      cytokine concentrations were higher than those found in the serum. In the PCOS
      women the follicular fluid tumor necrosis factor-alpha values were significantly
      and inversely correlated to the follicular fluid estradiol values (rho = -0.79; P
      <.001); this correlation was not found in the control subjects. CONCLUSION: In
      infertile women with PCOS, 1). serum and follicular fluid interleukin-6 and tumor
      necrosis factor-alpha values were higher than those found in control women, 2).
      the cytokine concentrations were higher in the follicular fluid than in the
      serum, and 3). the intrafollicular tumor necrosis factor-alpha concentrations
      were significantly and inversely correlated to the estradiol levels. These
      results suggest an involvement of the immune system in PCOS.

PMID- 12798523
TI  - Randomized clinical trial of extended spectrum antibiotic prophylaxis with
      coverage for Ureaplasma urealyticum to reduce post-cesarean delivery
      endometritis.
AB  - OBJECTIVE: To determine if extended spectrum prophylactic antibiotic treatment
      (with efficacy against Ureaplasma urealyticum) reduces post-cesarean delivery
      clinical endometritis. METHODS: After cord clamping at cesarean delivery,
      subjects received prophylaxis with cefotetan. Subjects were then simultaneously
      randomized (double blind) to receive doxycyline plus azithromycin versus placebo.
      Post-cesarean delivery endometritis was defined clinically as fever of 100.4F or
      higher with one or more supporting clinical signs or a physician diagnosis of
      endometritis plus the absence of a nonpelvic source of fever. RESULTS: A total of
      597 women were enrolled, 301 in the doxycycline/azithromycin group and 296 in the
      placebo group. The study population was 56% black, 25.5 +/- 6.2 years of age, and
      43% nulliparous. The groups were similar (P >.05) for black race, parity,
      maternal age, and most risk factors for post-cesarean delivery endometritis. The
      frequency of post-cesarean delivery endometritis (16.9% versus 24.7%, P =.020),
      wound infections (0.8% versus 3.6%, P =.030), and a combination of these two
      outcomes (19.0% versus 27.8%, P =.019) were significantly lower in the
      doxycycline/azithromycin group compared with the placebo-treated group. The
      doxycycline/azithromycin versus placebo groups were dissimilar for maternal
      leukocytosis (24.9% versus 12.5%, P =.042) and frequency of classic uterine
      incision (7.6% versus 12.5%, P =.048). Adjusting for these factors did not alter
      the risk ratio for post-cesarean delivery endometritis in the active versus
      placebo-treated group (relative risk 0.65, 95% confidence interval 0.43, 0.98).
      Length of stay was longer in the placebo group overall (104 +/- 56 versus 95 +/-
      32 hours, P =.016) and among women with endometritis (146 +/- 52 versus 127 +/-
      46 hours, P =.047). CONCLUSION: Extended spectrum prophylactic antibiotic
      treatment (with presumed efficacy against U urealyticum) given to women
      undergoing cesarean delivery at term shortens hospital stay and reduces the
      frequency of post-cesarean delivery endometritis and wound infections.

PMID- 12798524
TI  - Perinatal characteristics and outcomes of pregnancies complicated by twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: To assess the outcome of a geographically based cohort of
      monochorionic twin pregnancies complicated by twin-twin transfusion syndrome
      managed in a single perinatal center over a 10-year period. METHODS: A
      prospective cohort design was established in 1992 within a single tertiary
      obstetric unit. RESULTS: Sixty-nine cases of twin-twin transfusion syndrome were
      identified during the study period. The median gestation at diagnosis was 22.1
      weeks (interquartile range 19.7-25.4). Perinatal outcome was directly related to
      stage at diagnosis and gestation at delivery. The overall perinatal survival rate
      was 64.5%. For lesser disease severity (stages I and II) the perinatal survival
      rate was 76.4%, falling to 51.5% with increasing disease severity (stages III-V)
      (P =.004). The median gestation at delivery was 29.4 weeks (interquartile range
      26.3-33.8). The perinatal survival for those born at less than 28 weeks'
      gestation was 27.1%, increasing to 84.4% for those born at more than 28 weeks'
      gestation (P =.001). The incidence of neonatal complications reflected the high
      preterm birth rate. Amnioreduction was the principal intervention employed in
      this series, but in 24.6% of cases no therapy was used because of the requirement
      for immediate delivery or fetal demise. CONCLUSION: Twin-twin transfusion
      syndrome is a heterogeneous disorder in its clinical manifestations and progress.
      There remain significant perinatal mortality and morbidity in pregnancies
      complicated by twin-twin transfusion syndrome, principally related to the high
      preterm birth rate that typifies this disorder. The severity of disease as
      assessed by stage and the gestation at delivery are the principal factors in
      determining perinatal outcome in this condition.

PMID- 12798525
TI  - Fasting plasma glucose test at the first prenatal visit as a screen for
      gestational diabetes.
AB  - OBJECTIVE: To determine whether the fasting plasma glucose test administered at
      the first prenatal visit could serve as an efficient screen for gestational
      diabetes. METHODS: A total of 5557 women not known to have diabetes were offered
      a fasting plasma glucose test at their first prenatal visit. Results less than
      100 mg/dL were blinded. A glucose tolerance test was requested immediately of
      those whose screening test result was 100-125 mg/dL and of all women not
      identified as having diabetes by their 23rd gestational week. RESULTS: A total of
      4507 women (81%) complied with the protocol. Of the 302 women found to have
      gestational diabetes, 46 (15%) were detected before 24 weeks. A false-positive
      rate of 57% was found at a threshold fasting glucose concentration giving a
      sensitivity of 80% for the detection of gestational diabetes. CONCLUSION: The
      fasting plasma glucose screening test at the first prenatal visit has good
      patient compliance. However, its poor specificity (high false-positive rate)
      makes it an inefficient screening test for gestational diabetes.

PMID- 12798526
TI  - Physician cesarean delivery rates and risk-adjusted perinatal outcomes.
AB  - OBJECTIVE: To compare perinatal outcomes in obstetric practices with high and low
      cesarean delivery rates. METHODS: We conducted a population-based study based on
      171295 singleton births in New Jersey in 1996 and 1997. Vital certificate data
      for each birth were linked to the corresponding hospital discharge records.
      Nonsubspecialist obstetricians were divided into three groups based on their
      cesarean delivery rates during the study period: low (less than 18%), medium (18
      27%), and high (greater than 27%). Perinatal mortality, rates of birth injury,
      and uterine rupture were compared among the physician groups after adjustment for
      differences in patient risks. RESULTS: Physicians in the frequent cesarean
      delivery group performed more cesarean deliveries for all major indications.
      Perinatal mortality rates were comparable among the three physician groups. Low
      and very low birth weight infants delivered by the high-rate physicians did not
      have a lower risk of mortality. The risk of intracranial hemorrhage was
      significantly higher for infants delivered by low-rate physicians than for those
      delivered by medium-rate physicians (adjusted relative risk [RR] 1.53; 95%
      confidence interval [CI] 1.07, 2.19). Relative to deliveries by medium-rate
      physicians, deliveries by low-rate physicians were associated with a lower
      overall risk of uterine rupture (adjusted RR 0.56; 95% CI 0.34, 0.92). Medium-
      and high-rate groups had similar occurrences of birth injury and uterine rupture.
      CONCLUSION: Low cesarean delivery rates reduced the rate of uterine rupture and
      were not associated with increased perinatal mortality. The data suggest a small
      increase in intracranial hemorrhages in infants delivered by physicians who
      perform relatively few cesarean deliveries.

PMID- 12798527
TI  - A randomized placebo-controlled crossover trial with phytoestrogens in treatment
      of menopause in breast cancer patients.
AB  - OBJECTIVE: Phytoestrogens are popular in treatment of menopause, although
      scientific evidence is insufficient as to their efficacy. We studied the effects
      of daily use of isoflavonoids on climacteric symptoms and quality of life in
      patients with a history of breast cancer. METHODS: Sixty-two postmenopausal
      symptomatic women were randomized to use either phytoestrogen (tablets containing
      114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were
      reversed after a 2-month washout period. Fifty-six women completed the study.
      Menopausal symptoms were recorded on the Kupperman index and the visual analogue
      scale, and working capacity and mood changes were assessed via validated
      questionnaires. In addition, we followed the levels of phytoestrogens, follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone
      binding globulin. Liver enzymes and creatinine were also assessed at each visit.
      RESULTS: The phytoestrogen regimen raised the circulating levels of
      phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index
      was reduced by 4.2 +/- 9.6 (mean +/- standard deviation) (15.5%) during
      phytoestrogen use and similarly by 4.0 +/- 8.1 (14.7%) during placebo use (P
      nonsignificant). The quality of life parameters (working capacity, mood changes)
      were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused
      no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen
      treatment was well tolerated and caused no changes in liver enzymes, creatinine,
      body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the
      phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported
      no preference (nonsignificant). CONCLUSION: Pure isoflavonoids did not alleviate
      subjective menopausal symptoms in breast cancer patients.

PMID- 12798528
TI  - Alcohol consumption and the risk of borderline and invasive ovarian cancer.
AB  - OBJECTIVE: To examine the hypothesis that alcohol consumption is associated with
      the risk of ovarian cancer by conducting a population-based, case-control study
      in Hawaii and Los Angeles, California. METHODS: In-person interviews were
      obtained from 558 women with ovarian cancer and 607 population controls regarding
      lifetime alcohol consumption and other factors that may be related to the
      development of ovarian cancer. RESULTS: We found no overall association of
      alcohol drinking with the odds ratios (OR) for ovarian cancer. However, current
      alcohol drinkers, but not former drinkers, had a significantly lower OR for
      ovarian cancer compared with never drinkers (OR 0.69, 95% confidence interval
      [CI] 0.50, 0.96). Odds ratios for ovarian cancer associated with the current
      consumption of beer, wine, and spirits were also reduced, but were only
      significant for wine drinkers. Among current wine drinkers, women who drank red
      wine had a significantly reduced OR for ovarian cancer compared with never
      drinkers (OR 0.61, 95% CI 0.39, 0.94). The inverse association of current alcohol
      drinking with the OR for ovarian cancer was restricted to invasive tumors,
      especially the endometrioid cell type. The number of glasses of alcohol consumed
      on a weekly basis was inversely related to the OR for invasive ovarian cancer (P
      =.009): Current drinkers consuming 14 or more drinks per week had an OR of 0.36
      (95% CI 0.19, 0.70) compared with never drinkers. A significantly increased risk
      of borderline serous tumors was associated with the use of spirits (OR 2.66, 95%
      CI 1.46, 4.85). The risk for borderline mucinous tumors was also significantly
      elevated for former wine drinkers. CONCLUSIONS: These findings suggest that the
      association of alcohol consumption with the OR for ovarian cancer may vary by
      alcohol type, tumor invasiveness, and histology.

PMID- 12798529
TI  - Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained
      recurrent pregnancy loss.
AB  - OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24
      partners of women with unexplained recurrent pregnancy loss and to analyze the
      data in relation to sperm apoptosis data. METHODS: Semen quality parameters and
      sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated
      in the recurrent pregnancy loss patients, fertile controls, and a control group
      of men from the general population. RESULTS: The mean aneuploidy rate in the
      recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005)
      than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/-
      0.11) control groups. In the recurrent pregnancy loss patients, the percentage of
      aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P
      <.001). Normal morphology was diminished in the patient group, compared with the
      general population group (P <.01) and the donor group (P <.001). CONCLUSIONS:
      These data indicate that some recurrent pregnancy loss patients have a
      significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal
      sperm morphology. This study demonstrates a new possible cause of recurrent
      pregnancy loss.

PMID- 12798530
TI  - Pregnancy outcome in recurrent miscarriage patients with skewed X chromosome
      inactivation.
AB  - OBJECTIVE: To analyze X inactivation in women with recurrent miscarriage to
      estimate whether skewed X inactivation is associated with recurrent miscarriage
      and whether it predicts next pregnancy outcomes. METHODS: A multicenter study was
      performed. A power calculation determined that 101 patients were needed to detect
      a difference in skewed X inactivation between patients and controls. Patients
      were entered into a prospective trial of mononuclear-cell immunotherapy and
      subsequently tested for skewed X inactivation. Age-matched controls had one live
      birth and no prior miscarriages. Results from our X inactivation assay were
      compared with those from an independent genetics laboratory. RESULTS: Greater
      than 75% skewing was seen in 22.6% of patients and 26.5% controls (P =.52).
      Greater than 90% skewing was seen in 6.6% of patients and 3.9% of controls (P
      =.77). There were 19.8% of primary aborters and 32% of secondary aborters with
      greater than 75% skewed X inactivation (P =.38). There were 4.9% of primary
      aborters and 12.0% of secondary aborters with greater than 90% skewed X
      inactivation (P =.27) Neither greater than 75% nor greater than 90% skewed X
      inactivation impacted next pregnancy outcomes (odds ratios = 0.87 [95% confidence
      interval (CI) 0.34, 2.3] and 1.4 [95% CI 0.27, 7.5], respectively). Results of
      the exchange of samples with an independent laboratory were highly correlated
      (alpha = 0.987, P <.001, coefficient of variation = 5.5%). CONCLUSION: Skewed X
      chromosome inactivation is not associated with recurrent miscarriage. A patient's
      X chromosome inactivation status does not predict next pregnancy outcome. Our
      assay correlates with another experienced laboratory.

PMID- 12798531
TI  - Training and competency assessment in electronic fetal monitoring: a national
      survey.
AB  - OBJECTIVE: To investigate current patterns of training and competency assessment
      in electronic fetal monitoring (EFM) for obstetrics and gynecology residents and
      maternal-fetal medicine fellows. METHODS: A questionnaire was mailed to the
      directors of all 254 accredited US residencies in obstetrics and gynecology and
      61 accredited US fellowships in maternal-fetal medicine. Questions focused on the
      methods used for teaching and assessing competency in EFM. RESULTS: Two hundred
      thirty-nine programs (76%) responded to the survey. Clinical experience is used
      by 219 programs (92%) to teach EFM, both initially and on an ongoing basis.
      Significantly more residencies than fellowships use written materials and
      lectures to teach EFM. More than half of all programs require trainees to
      participate in some type of EFM training at least every 6 months; 23 programs
      (10%) have no requirement at all. Subjective evaluation is used by 174 programs
      (73%) to assess competency in EFM. Written or oral examinations, skills
      checklists, and logbooks are used exclusively by residencies as means of
      competency assessment. Two thirds of all programs assess EFM skills at least
      every 6 months; 40 programs (17%), the majority of which are fellowships, have no
      formal requirement. CONCLUSION: Most US training programs use supervised clinical
      experience as both their primary source of teaching EFM and their principal
      competency assessment tool. Residencies are more likely to have formal
      instruction and assessment than are fellowships. Few programs are using novel
      strategies (eg, computers or simulators) in their curriculum.

PMID- 12798532
TI  - Association of prematurity and neonatal infection with neurologic morbidity in
      very low birth weight infants.
AB  - OBJECTIVE: To identify risk factors predictive of neurologic morbidity in very
      low birth weight (VLBW) infants. METHODS: This is a case-control study of all
      infants weighing 1500 g or less admitted to a single tertiary neonatal intensive
      care unit between April 1999 and December 2001. The case group were those
      neonates with neurologic morbidity including intraventricular hemorrhage,
      seizures, hydrocephalus, and periventricular leukomalacia. The control group were
      those without neurologic morbidity. Wilcoxon rank-sum, Fisher exact test, chi(2),
      and univariate and stepwise multiple logistic regression were performed, with P <
      0.05 considered significant. RESULTS: Of 213 VLBW infants, 77 had neurologic
      morbidity: 61 had intraventricular hemorrhage, eight had seizures, 13 had
      hydrocephalus, and nine had periventricular leukomalacia. Several infants had
      more than one morbidity. Gestational age (odds ratio [OR] 0.95; 95% confidence
      interval [CI] 0.94, 0.96; P <.005), birth weight (OR 0.62; 95% CI 0.49, 0.79; P
      <.005), and neonatal infection (OR 1.36; 95% CI 1.17, 1.58; P <.005) were highly
      associated with neurologic morbidity. There was no difference in mean umbilical
      arterial cord pH (7.25 +/- 0.15, 7.28 +/- 0.09, P =.45) or base excess (-3.8 +/-
      4.8 mEq/L, -2.3 +/- 3.0, P =.10). Only three of 52 infants (5.8%) in the case
      group had an umbilical arterial pH of less than 7. CONCLUSION: Prematurity and
      neonatal infection were the dominant factors associated with neurologic morbidity
      in VLBW infants. Intrapartum acidosis occurred in less than 6% of those with
      neurologic morbidity.

PMID- 12798533
TI  - Predicting term and preterm delivery with transabdominal uterine
      electromyography.
AB  - OBJECTIVE: To determine whether delivery can be predicted using transabdominal
      uterine electromyography. METHODS: A total of 99 patients were grouped as either
      term (37 weeks or more) or preterm (less than 37 weeks). Uterine electrical
      activity was recorded for 30 minutes in clinic. Electromyographic "bursts" were
      evaluated to determine the power density spectrum. Measurement-to-delivery time
      was compared with the average power density spectrum's peak frequency. Receiver
      operating characteristic curve analysis was performed for 48, 24, 12, and 8 hours
      from term delivery, and 6, 4, 2, and 1 day(s) from preterm delivery. RESULTS: The
      power density spectrum peak frequency increased as the measurement-to-delivery
      interval decreased. Receiver operating characteristic curve analysis gave high
      positive and negative predictive values for both term and preterm delivery. At
      term, the average power density spectrum peak frequency was significantly higher
      for the 24-or-fewer-hours-to-delivery group than for the more-than-24-hours-to
      delivery group, whereas at preterm, the average power density spectrum peak
      frequency was significantly higher in the 4-or-fewer-days-to-delivery group than
      in the more-than-4-days-to-delivery group (P <.05). CONCLUSION: Transabdominal
      uterine electromyography predicts delivery within 24 hours at term and within 4
      days preterm. This methodology offers many advantages and benefits that are not
      available with present uterine monitoring systems.

PMID- 12798534
TI  - Effect of maternal hydration on amniotic fluid volume.
AB  - OBJECTIVE: To estimate the effects of maternal intravenous hydration on amniotic
      fluid volume in normal pregnancies. METHODS: Women undergoing an amniocentesis
      for the evaluation of fetal lung maturity before an elective cesarean delivery
      were eligible to participate. An amniotic fluid index (AFI) was obtained before
      the amniocentesis, and at the time of the amniocentesis the amniotic fluid (AF)
      volume was determined by diazo-dye reaction with subsequent spectrophotometric
      analysis of AF samples. If the AF sample drawn for fetal maturity studies was
      mature, the patient was hydrated with 1000 mL of balanced salt solution 30
      minutes before her cesarean delivery. Amniotic fluid volume was subsequently
      estimated after the hydration by a repeat AFI. Amniotic fluid volume was directly
      measured at cesarean delivery and compared with the dye-determined volume. The
      pre- and posthydration AFI were also compared. RESULTS: A total of 17 women
      participated in the study between January 2001 and June 2001. Statistically
      significant increases in the AF volume and AFI were found. The prehydration
      median AF volume was 450 mL (range 250-953), and the median increase in AF volume
      was 188 mL (95% confidence interval [CI] 60, 254 mL; P <.001). Median AFI was 8.6
      (range 5.8-17.8) with a median change in AFI of 1.7 cm (95% CI 1.1, 3.0; P
      <.001). CONCLUSION: Maternal intravenous hydration appears to increase both the
      actual and ultrasound-estimated AF volumes in normal third-trimester pregnancies.

PMID- 12798536
TI  - Patient rotation and resolution of unilateral cornual obstruction during
      hysterosalpingography.
AB  - OBJECTIVE: Unilateral obstruction of the proximal fallopian tube is identified in
      10-24% of patients undergoing hysterosalpingography for evaluation of
      infertility. Upon further testing, this obstruction spontaneously resolves 16-80%
      of the time. We hypothesized that patient rotation during hysterosalpingography
      might resolve proximal tubal obstruction in some cases by altering either the
      location of intrauterine air bubbles or the spatial relationship of the tube to
      the uterine fundus. METHODS: In patients in whom unilateral proximal tubal
      obstruction was detected during hysterosalpingography performed for standard
      clinical indications, the patient was rotated on her hip approximately 45 degrees
      such that the obstructed tube was first superior (ventral) to the patent tube,
      and dye was reinjected. If obstruction did not resolve, the patient was rotated
      in the opposite direction so that the obstructed tube was inferior (dorsal) to
      the patent tube and dye reinjected. RESULTS: Unilateral tubal obstruction was
      found in 15% of cases (24 of 156). Rotating the patient with obstructed tube
      superior to the patent tube never resulted in tubal patency, whereas rotating the
      patient with the obstructed tube inferior resulted in resolution of tubal patency
      in 63% of cases (15 of 24) CONCLUSION: . Unilateral cornual obstruction during
      hysterosalpingography is often resolved by rotating the patient such that the
      obstructed tube is more inferior. Although this observation may be the result of
      dislodging smaller air bubbles, from a fluid dynamics perspective a more likely
      explanation is unkinking of the more inferior tube.

PMID- 12798535
TI  - Second-trimester maternal serum placental growth factor and vascular endothelial
      growth factor for predicting severe, early-onset preeclampsia.
AB  - OBJECTIVE: To determine whether alterations in second-trimester maternal serum
      cytokine concentrations can identify women at risk for developing severe, early
      onset preeclampsia. METHODS: Patients with severe preeclampsia requiring delivery
      prior to 34 weeks (n = 20) were each matched by gestational age, gravidity,
      parity, and sample freezing time with three healthy controls who delivered at
      term (n = 60). By using second-trimester maternal sera originally collected for
      fetal aneuploidy screening, the concentrations of placental growth factor,
      vascular endothelial growth factor, granulocyte colony-stimulating factor,
      endothelin-1, and human chorionic gonadotropin were compared between patients and
      controls. Logistic regression analysis was used to estimate odds ratios for high
      versus low (median split) cytokine concentrations with respect to the development
      of severe, early-onset preeclampsia. Receiver operating characteristic (ROC)
      curves based on a second logistic regression, using actual cytokine values, were
      plotted to illustrate reciprocal impact on sensitivity and specificity. RESULTS:
      Placental growth factor and vascular endothelial growth factor levels were
      significantly lower in patients than in controls. No significant differences were
      observed for the other cytokines. The odds ratios (with 95% confidence intervals)
      were 15.54 (3.29, 73.40) for vascular endothelial growth factor and 4.20 (1.35,
      13.06) for placental growth factor. Receiver operating characteristic analysis of
      placental growth factor and vascular endothelial growth factor confirmed that
      both were useful in discriminating between patients and controls. Models
      combining both vascular endothelial growth factor and placental growth factor
      provided the best performance for identifying patients at risk for developing
      severe, early-onset preeclampsia, according to both odds ratios and ROC analyses.
      CONCLUSION: Combined analysis of placental growth factor and vascular endothelial
      growth factor is potentially useful as a tool for early identification of
      patients at risk for developing severe, early-onset preeclampsia.

PMID- 12798537
TI  - Predicting treatment choice for patients with pelvic organ prolapse.
AB  - OBJECTIVE: To evaluate which clinical factors were predictive of treatment choice
      for patients with pelvic organ prolapse. METHODS: One hundred fifty-two patients
      were enrolled in this cross-sectional study to collect clinical data on potential
      predictors of treatment choice. Continuous parametric, continuous nonparametric
      (ordinal), and categoric data were compared with chosen management plan
      (expectant, pessary, surgery) using analysis of variance, the Kruskal-Wallis
      test, and the chi(2) test for association, respectively. All significant
      predictors (P <.05) of treatment choice for pelvic organ prolapse identified
      during univariate analysis were entered into a backward elimination polytomous
      logistic regression analysis for predicting surgery versus pessary versus
      expectant management, with surgery as the reference group. RESULTS: The
      probability of choosing expectant management rather than surgery 1). increases as
      the preoperative pelvic pain score increases (odds ratio [OR] 1.6; 95% confidence
      interval [CI] 1.07, 2.40; P =.024) and 2). decreases as the prolapse severity
      increases (OR 0.46; 95% CI 0.29, 0.72; P =.001). The probability of choosing
      pessary rather than surgery 1). increases as age increases (OR 1.1; 95% CI 1.05,
      1.16; P <.001), 2). decreases as the prolapse severity increases (OR 0.77; 95% CI
      0.60, 0.99; P =.042), and 3). is less if the participant had prior prolapse
      surgery (OR 0.23; 95% CI 0.07, 0.76; P =.017). CONCLUSION: Age, prior prolapse
      surgery, preoperative pelvic pain scores, and pelvic organ prolapse severity were
      independently associated with treatment choices in a predictable way and provide
      physicians with medical evidence necessary to support a patient's decision.

PMID- 12798538
TI  - Vulvar mucus observations and the probability of pregnancy.
AB  - OBJECTIVE: To assess the day-specific and cycle-specific probabilities of
      conception leading to clinical pregnancy, in relation to the timing of
      intercourse and vulvar mucus observations. METHODS: This was a retrospective
      cohort study of women beginning use of the Creighton Model Fertility Care System
      in Missouri, Nebraska, Kansas, and California. Data were abstracted from
      Creighton Model Fertility Care System records, including women's daily
      standardized vulvar observations of cervical mucus discharge, days of
      intercourse, and clinically evident pregnancy (conception). Established
      statistical models were used to estimate day-specific probabilities of
      conception. RESULTS: Data were analyzed from 1681 cycles with 81 conceptions from
      309 normally fertile couples (initially seeking to avoid pregnancy) and from 373
      cycles with 30 conceptions from 117 subfertile couples (who were initially trying
      to achieve pregnancy). The highest probability of pregnancy occurred on the peak
      day of vulvar mucus observation (.38 for normally fertile couples and.14 for
      subfertile couples). The probability of pregnancy was greater than.05 for
      normally fertile couples from 3 days before to 2 days after the peak, and for
      subfertile couples from 1 day before to 1 day after the peak. The cycle-specific
      probability of conception correlated with the quality of mucus discharge in
      normally fertile couples but not in subfertile couples. CONCLUSION: Standardized
      vulvar observations of vaginal mucus discharge identify the days with the
      greatest likelihood of conception from intercourse in normal fertility and
      subfertility and provide an indicator of the overall potential for conception in
      a given menstrual cycle in normal fertility.

PMID- 12798539
TI  - A comparison of oral misoprostol with vaginal misoprostol administration in
      second-trimester pregnancy termination for fetal abnormality.
AB  - OBJECTIVE: To compare the clinical efficacy and side effects of oral misoprostol
      with vaginal misoprostol for second-trimester pregnancy termination. METHODS: A
      randomized clinical trial of medical pregnancy termination between 14 and 26
      weeks' gestation was conducted. Three misoprostol regimens were compared: 400
      microg vaginally at 6-hour intervals (group 1), 400 microg orally at 3-hour
      intervals (group 2), and a loading dose of 600 microg vaginally followed by 200
      microg orally at 3-hour intervals (group 3). A sample size of 225 women was
      required for equivalence of the three regimens, with an interim safety analysis
      planned at 80 women. RESULTS: A significant difference between the groups was
      evident at the interim safety analysis and the study ceased. The subset of 84
      women recruited before the study closure is described. There was a significant
      difference in the median time to achieve delivery among the three groups: group
      1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours
      (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P
      =.042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group
      2, and 74.1% in group 3 delivered (P =.003). At 48 hours 0% in group 1, 20.7% in
      group 2, and 3.7% in group 3 were undelivered (P =.011). There was no difference
      in women's perceptions of the termination process. CONCLUSION: In second
      trimester pregnancy termination, a vaginal misoprostol regimen of 400 microg
      every 6 hours was 1.9 times more likely to result in delivery within 24 hours
      from commencement than an oral regimen of 400 microg every 3 hours.

PMID- 12798540
TI  - The implications of a false positive second-trimester serum screen for Down
      syndrome.
AB  - OBJECTIVE: To investigate the genetic and obstetric implications of false
      positive Down syndrome serum screening results. METHODS: The study population
      comprised 162774 women underwent triple marker screening in the Ontario Maternal
      Serum Screening program between October 1995 and September 1998, with outcomes
      obtained from the Canadian Institute of Health Information. The study compares
      the incidence of chromosomal abnormalities other than Down syndrome in screen
      positive women with background incidence from the literature. It also compares
      the risks of having a fetus with congenital abnormalities or of developing
      obstetric complications in 11549 screen positive women with their matched
      controls. RESULTS: A higher incidence of trisomy 13 (12.4 per 10000) was seen in
      screen positive women; the incidence of other chromosomal abnormalities in screen
      positive women was not increased relative to the general population. The higher
      incidence of trisomy 13 may have been biased by the selective uptake of
      amniocentesis in women who had high risks for Down syndrome or abnormal
      ultrasound findings. Incidences of fetal congenital abnormality in screen
      positive and negative women were similar. Women who screened positive for Down
      syndrome had increased risk of spontaneous fetal loss (odds ratio 1.80; 95%
      confidence interval 1.54, 2.07) but no other obstetric complications. CONCLUSION:
      Among women who screened positive for Down syndrome, we found a higher number of
      spontaneous fetal losses and a possibly higher risk of having a fetus with
      trisomy 13. We did not find an increased risk for other chromosomal
      abnormalities, congenital abnormalities, or other adverse obstetric outcomes.

PMID- 12798541
TI  - A longitudinal study of maternal dose response to low molecular weight heparin in
      pregnancy.
AB  - OBJECTIVE: To assess the maternal response to low molecular weight heparin during
      pregnancy, by estimation of plasma anti-Xa activity, at three specified gestation
      points and in the nonpregnant state. METHODS: A longitudinal, prospective,
      observational study was set in a tertiary referral recurrent miscarriage clinic.
      Twenty-four women, attending consecutively, were invited to participate and gave
      informed consent. Each woman had a history of recurring pregnancy loss and
      positive preconception screening for antiphospholipid syndrome. After
      confirmation of a viable pregnancy all subjects began taking 5000 IU of
      dalteparin once daily subcutaneously. Serial measurement of plasma anti-Xa
      activity after administration of dalteparin was performed at three standard
      gestation points (12, 24, and 36 weeks) and in the nonpregnant state (6 weeks
      postpartum). RESULTS: Peak anti-Xa levels occurred at 4 hours postbolus in
      pregnancy, as compared with 2 hours in the nonpregnant state. The mean anti-Xa
      levels at 12, 24, and 36 weeks' gestation were significantly reduced, at 2 hours
      postinjection, as compared with the nonpregnant state (P <.001, P <.01, P <.001,
      respectively). The lowest dose-response curve was at 36 weeks' gestation. A
      repeated-measures analysis of variance found a significant difference (P <.05)
      between the 36-week group and the postterm group but not between any of the other
      groups. CONCLUSION: During pregnancy, differences in the pharmacokinetics of low
      molecular weight heparin were observed, with an overall reduction in anti-Xa
      activity. On the basis of this study it is questionable to extrapolate dosing and
      lack of dose monitoring, in pregnant women, using data derived from a nonpregnant
      population.

PMID- 12798542
TI  - Labor induction versus expectant management for postterm pregnancies: a
      systematic review with meta-analysis.
AB  - OBJECTIVE: To compare routine labor induction with expectant management for
      patients who reach or exceed 41 weeks' gestation. DATA SOURCES: Computerized
      databases, references in published studies, and textbook chapters in all
      languages were used to identify randomized controlled trials (RCTs) evaluating
      induction and expectant management of labor for postterm pregnancies. METHODS OF
      STUDY SELECTION: We identified RCTs that compared induction and expectant
      management for uncomplicated, singleton, live pregnancies of at least 41 weeks'
      gestation and evaluated at least one of the following: perinatal mortality, mode
      of delivery, meconium-stained fluid, meconium aspiration syndrome, meconium below
      the cords, fetal heart rate (FHR) abnormalities during labor, cesarean deliveries
      for FHR abnormalities, abnormal Apgar scores, and neonatal intensive care unit
      (NICU) admissions. The primary outcomes assessed were cesarean delivery rate and
      perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Sixteen studies met
      inclusion criteria for this review. For each study with binary outcomes, an odds
      ratio (OR) with 95% confidence intervals (CIs) was calculated for selected
      outcomes. Estimates of ORs for dichotomous outcomes were calculated using fixed
      and random-effects models. Homogeneity was tested across the studies. Compared
      with women allocated to expectant management, those who underwent labor induction
      had lower cesarean delivery rates (20.1% versus 22.0%) (OR 0.88; 95% CI 0.78,
      0.99). Although subjects whose labor was induced experienced a lower perinatal
      mortality rate (0.09% versus 0.33%) (OR 0.41; 95% CI 0.14, 1.18), this difference
      was not statistically significant. Similarly, no significant differences were
      noted for NICU admission rates, meconium aspiration, meconium below the cords, or
      abnormal Apgar scores. CONCLUSION: A policy of labor induction at 41 weeks'
      gestation for otherwise uncomplicated singleton pregnancies reduces cesarean
      delivery rates without compromising perinatal outcomes.

PMID- 12798543
TI  - Aspirin for prevention of preeclampsia in women with historical risk factors: a
      systematic review.
AB  - OBJECTIVE: To examine the effectiveness of aspirin in preventing perinatal death
      and preeclampsia in women with predisposing historical risk factors, such as
      previous history of preeclampsia, chronic hypertension, diabetes, and renal
      disease. DATA SOURCES: Searches were conductes in Medline, Embase, Cochrane
      Library, National Research Register, SCISEARCH, AND ISI Conference Proceedings
      without any language restrictions, using the following medical subject headings
      and text words: "aspirin," "antiplatelet*," "salicyl*," "acetylsalicyl*,"
      "platelet aggregation inhibitors," "pre-eclamp*," "preeclamp*," and "hypertens*.
      METHODS OF STUDY SELECTION: We included all randomized trials that evaluated the
      effectiveness of aspirin compared with placebo or no treatment in women with
      predisposing historical risk factors and reported clinically relevant perinatal
      or maternal outcomes. Study selection, quality appraisal, and data extractions
      were performed independently and in duplicate.We identified 14 relevant trials,
      including a total of 12,416 women. Meta-analysis showed a significant benefit of
      aspirin therapy in reducing perinatal death (odds ratio [OR] 0.79, 95% confidence
      interval [CI] 0.64, 0.96) and preeclampsia (OR 0.86, 95% CI 0.76, 0.96). Aspirin
      was also associated with a reduction in rates of spontaneous preterm birth (OR
      0.86, 95% CI 0.79, 0.94), and an increase of 215 g in mean birth weight (weighted
      mean difference 215, 95% CI 90, 341). There was no increase in the risk of
      placental abruption with aspirin (OR 0.98, 95% CI 0.79, 1.21). Funnel plot
      analysis indicated that publication and related biases were unlikely (Egger test,
      P =.84). CONCLUSION: Aspirin reduces the risk of perinatal death and preeclampsia
      in women with historical risk factors. Given the importance of these outcomes and
      the safety and low cost of aspirin, aspirin therapy should be considered in women
      with historical risk factors.

PMID- 12798544
TI  - Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.
AB  - Antiphospholipid syndrome, a condition characterized by one or more thrombotic or
      pregnancy-related clinical features in association with medium to high levels of
      antiphospholipid antibodies, has emerged as an important diagnostic consideration
      in several medical fields. Antiphospholipid syndrome is one of the few treatable
      causes of pregnancy loss, and successful pregnancy rates of 70% or more can be
      achieved with appropriate treatment. Heparin, usually combined with low-dose
      aspirin, is used in patients at risk for thrombosis. Pregnancy in these women is
      associated with increased rates of preeclampsia, placental insufficiency, and
      preterm delivery, so that attentive clinical care is required for best outcomes.
      Recent studies indicate that women at low risk for thrombosis may be treated with
      low-dose aspirin. However, remaining controversies and unanswered questions in
      the field of antiphospholipid syndrome are a source of clinical confusion. This
      review highlights the most important controversies, taking into account the
      results of recent obstetric treatment trials and our own clinical experience.

PMID- 12798545
TI  - "Bust enhancing" herbal products.
AB  - "Bust enhancing" herbal products are widely advertised. No clinical trials have
      been published. These products contain a variety of ingredients, including
      grains, hops, saw palmetto, dong quai, chaste-tree berry, wild yam, kava, fennel,
      black cohosh, and fenugreek. Several of these herbs are hormonally active; for
      example, hops contain 8-prenylnaringenin, a phytoestrogen that is more potent
      than other dietary phytoestrogens. Many bust-enhancing dietary supplements
      contain substrates for Fusarium, a fungus that produces zearalenone, a potent
      estrogen that has been associated with breast enlargement in humans and other
      species. The use of bust-enhancing products should be discouraged because of lack
      of evidence for efficacy and long-term safety concerns.

PMID- 12798546
TI  - Clinical evaluation of a "hand pump" vacuum delivery device.

PMID- 12798547
TI  - A randomized trial of oral and vaginal misoprostol to manage delivery in cases of
      fetal death.

PMID- 12798549
TI  - Cervical cancer: effect of glandular cell type on prognosis, treatment, and
      survival.

PMID- 12798551
TI  - Problems with intrapartum fetal heart rate monitoring interpretation and patient
      management.

PMID- 12798552
TI  - 34th Bethesda Conference: Executive summary--can atherosclerosis imaging
      techniques improve the detection of patients at risk for ischemic heart disease?

PMID- 12798553
TI  - 34th Bethesda Conference: Task force #1--Identification of coronary heart disease
      risk: is there a detection gap?

PMID- 12798554
TI  - 34th Bethesda Conference: Task force #2--What is the pathologic basis for new
      atherosclerosis imaging techniques?

PMID- 12798555
TI  - 34th Bethesda Conference: Task force #3--What is the spectrum of current and
      emerging techniques for the noninvasive measurement of atherosclerosis?

PMID- 12798556
TI  - 34th Bethesda Conference: Task force #4--How do we select patients for
      atherosclerosis imaging?

PMID- 12798557
TI  - 34th Bethesda Conference: Task force #5--Is atherosclerosis imaging cost
      effective?

PMID- 12798558
TI  - Enhanced external counterpulsation for ischemic heart disease: what's behind the
      curtain?
AB  - Enhanced external counterpulsation (EECP) has been shown to reduce angina and to
      improve objective measures of myocardial ischemia in patients with refractory
      angina. Prospective clinical studies and large treatment registries suggest that
      a course of EECP is associated with prolongation of the time to exercise-induced
      ST-segment depression and resolution of myocardial perfusion defects, as well as
      with enhanced exercise tolerance and quality of life. With a growing knowledge
      base supporting the safety and beneficial clinical effects associated with EECP,
      this therapy can be considered a valuable treatment option, particularly in
      patients who have exhausted traditional revascularization methods and yet remain
      symptomatic despite optimal medical care. However, although the concept of
      external counterpulsation was introduced almost four decades ago, and despite
      growing evidence supporting the clinical benefit and safety of this therapeutic
      modality, little is firmly established regarding the mechanisms responsible for
      the beneficial effects associated with this technique. Suggested mechanisms
      contributing to the clinical benefit of EECP include improvement in endothelial
      function, promotion of coronary collateralization, enhancement of ventricular
      function, peripheral effects similar to those observed with regular physical
      exercise, and nonspecific placebo effects. This review summarizes the current
      evidence for a contribution of these mechanisms to the clinical benefit
      associated with EECP.

PMID- 12798559
TI  - The effect of atrial pacing therapies on atrial tachyarrhythmia burden and
      frequency: results of a randomized trial in patients with bradycardia and atrial
      tachyarrhythmias.
AB  - OBJECTIVES: The Atrial Therapy Efficacy and Safety Trial (ATTEST) was a
      prospective, randomized study to evaluate preventive pacing and antitachycardia
      pacing (ATP) in patients with symptomatic atrial fibrillation (AF) or atrial
      tachycardia (AT). BACKGROUND: The effect of the combination of atrial prevention
      and termination algorithms on AT/AF burden and frequency in pacemaker patients is
      unknown. METHODS: A DDDRP pacemaker (AT500, Medtronic Inc., Minneapolis,
      Minnesota) with three atrial preventive pacing algorithms and two ATP algorithms
      was implanted in 368 patients. Patients were randomized one-month post-implant to
      all prevention and ATP therapies ON or OFF and followed for three months. The OFF
      group had DDDR pacing at a lower programmed rate of 60 ppm. The AT/AF burden and
      frequency were determined from daily device counters in 324 patients treated
      according to protocol. RESULTS: In 17,018 episodes with stored electrograms,
      appropriate detection was confirmed in 17,004 (99.9%). The median percentage of
      atrial pacing was 98% in the ON group versus 75% in the OFF group (p < 0.001).
      Using device-defined criteria for successful termination, ATP terminated 8,590
      (54%) of 15,789 treated episodes. The median AT/AF burden during the three-month
      study period was 4.2 h/month ON versus 1.1 h/month OFF (p = 0.20). The median
      AT/AF frequency was 1.3 episodes/month ON versus 1.2 episodes/month OFF (p =
      0.65). System-related, complication-free survival at four months was 90.2%
      (Kaplan-Meier estimate). CONCLUSIONS: This DDDRP pacemaker is safe, has accurate
      AT/AF detection, and provides ATP with 54% efficacy as defined by the device. The
      atrial prevention and termination therapies combined did not reduce AT/AF burden
      or frequency in this patient population.

PMID- 12798560
TI  - Anemia predicts mortality in severe heart failure: the prospective randomized
      amlodipine survival evaluation (PRAISE).
AB  - OBJECTIVES: Our aim was to examine the relationships between serum hematocrit
      (Hct) and risk of all-cause mortality among patients with severe heart failure
      (HF). BACKGROUND: Anemia occurs with increased frequency in severe HF. However,
      few studies have examined the impact of anemia on mortality in this population.
      METHODS: Using a prospective cohort design, we evaluated the relationships
      between baseline serum Hct and mortality among 1,130 patients with left
      ventricular EF <30% and New York Heart Association functional class IIIB or IV HF
      treated with angiotensin-converting enzyme inhibitors, diuretics, and digitalis.
      Mortality was ascertained by centralized adjudication. RESULTS: The mean Hct was
      41.8% (range 25.4% to 58.8%). Over 15 months of mean follow-up, there were 407
      deaths (29 per 100 person-years). After adjustment for potential confounders,
      those in the lowest quintile of Hct (range 25.4% to 37.5%) had a 52% higher risk
      of death (hazard ratio 1.52, 95% confidence interval 1.11 to 2.10), compared with
      the highest quintile (range 46.1% to 58.8%). Within the lowest quintile of Hct,
      each 1% decrease in Hct was associated with an 11% higher risk of death (p <
      0.01), whereas within the four higher quintiles of Hct, Hct was not associated
      with total mortality. Evaluation of different causes of death indicated that a
      lower Hct was strongly associated with death from progressive HF, rather than
      sudden death or other deaths. CONCLUSIONS: Among patients with severe HF, anemia
      is a significant independent risk factor for death, with a progressively higher
      risk with increasing severity of anemia. Further investigation of the etiologies,
      prevention, and treatment of anemia in severe HF is warranted.

PMID- 12798561
TI  - Contemporary utilization and outcomes of intra-aortic balloon counterpulsation in
      acute myocardial infarction: the benchmark registry.
AB  - OBJECTIVES: We sought to examine contemporary utilization patterns and clinical
      outcomes in patients with acute myocardial infarction (AMI) requiring intra
      aortic balloon pump (IABP) counterpulsation. BACKGROUND: Despite increasing
      experience with and broadened indications for intra-aortic counterpulsation, the
      current indications, associated complications, and clinical outcomes of IABP use
      in AMI are unknown. METHODS: Between June 1996 and August 2001, data were
      prospectively collected from 22,663 consecutive patients treated with aortic
      counterpulsation at 250 medical centers worldwide; 5,495 of these patients had
      AMI. RESULTS: Placement of an IABP in AMI patients was most frequently indicated
      for cardiogenic shock (27.3%), hemodynamic support during catheterization and/or
      angioplasty (27.2%) or prior to high-risk surgery (11.2%), mechanical
      complications of AMI (11.7%), and refractory post-myocardial infarction unstable
      angina (10.0%). Balloon insertions were successful in 97.7% of patients.
      Diagnostic catheterization was performed in 96% of patients, and 83% underwent
      coronary revascularization before hospital discharge. The in-hospital mortality
      rate was 20.0% (38.7% in patients with shock) and varied markedly by indication
      and use of revascularization procedures. Major IABP complications occurred in
      only 2.7% of patients, despite median use for three days, and early IABP
      discontinuation was required in only 2.1% of patients. CONCLUSIONS: With
      contemporary advances in device technology, insertion technique, and operator
      experience, IABP counterpulsation may be successfully employed for a wide variety
      of conditions in the AMI setting, providing significant hemodynamic support with
      rare major complications in a high-risk patient population.

PMID- 12798562
TI  - Intra-aortic balloon counterpulsation in acute myocardial infarction: too few or
      too many?

PMID- 12798563
TI  - Poverty, process of care, and outcome in acute coronary syndromes.
AB  - OBJECTIVES: We sought to determine whether income-based disparities in care
      processes and outcome exist in patients with acute coronary syndromes.
      BACKGROUND: Using income proxies and limited clinical data, some observational
      studies have shown income disparities in outcome after acute myocardial
      infarction (MI). METHODS: Using annual household income from the economic
      substudy of the PURSUIT (Platelet Glycoprotein IIB/IIIA In Unstable Angina:
      Receptor Suppression Using Integrilin Therapy) trial, patients were grouped into
      low-, middle-, and high-income categories based on the U.S. Census Bureau
      definition of poverty. Logistic regression analysis was used to examine the
      association between income category and the use of cardiac procedures and the
      prescription of evidence-based medications at hospital discharge. Cox regression
      analysis was used to examine the hazard of 30-day and six-month death or
      recurrent MI across income categories, after adjusting for baseline
      characteristics. RESULTS: Low-income patients had more chronic medical conditions
      and were sicker at presentation. Among low-income patients, the use of some
      evidence-based medications and cardiac procedures was lower and the unadjusted
      rates of 30-day death and six-month death or MI was higher. After multivariable
      adjustment, there was no consistent pattern for disparity in care processes, but
      the trend for higher short and intermediate-term death or MI persisted for low
      income patients. CONCLUSIONS: Income level is associated with a trend toward
      worse outcome among patients with acute coronary syndromes. The disparity in 30
      day and six-month death or MI between low and high-income patients could not be
      readily explained by differences in in-hospital medical or invasive treatment,
      suggesting that the poor outcomes may be due to differences occurring after
      hospital discharge.

PMID- 12798564
TI  - Poverty and mortality in patients with acute coronary syndromes: a search for
      answers and a call for action.

PMID- 12798565
TI  - Angiotensin I-converting enzyme (ACE) inhibitors and restenosis after coronary
      artery stenting in patients with the DD genotype of the ACE gene.
AB  - OBJECTIVES: We tested the hypothesis that patients with the DD genotype of the
      angiotensin I-converting enzyme (ACE) gene who are treated with ACE inhibitors
      are at a higher risk of restenosis after coronary stent placement than patients
      who do not receive ACE inhibitors. BACKGROUND: Two recent studies with a limited
      series of patients carrying the DD genotype suggested an unfavorable impact of
      the use of ACE inhibitors on the restenotic process after implantation of stents
      in coronary arteries. Because these findings may question the use of ACE
      inhibitors after coronary stenting, we examined this important issue in a large
      series of patients. METHODS: We determined the ACE gene I/D genotype of 2,222
      consecutive patients with symptomatic coronary artery disease who underwent stent
      implantation. The patients with the DD genotype (n = 612) constituted the study
      population. The primary end point was in-stent restenosis, which was assessed as
      angiographic restenosis (> or =50% diameter stenosis at six-month follow-up) and
      clinical restenosis (need for target vessel revascularization due to symptoms or
      signs of ischemia in the presence of angiographic restenosis over one year after
      the intervention). RESULTS: Of the 612 patients with the DD genotype, 403 (65.8%)
      were treated with ACE inhibitors and 209 (34.2%) did not receive ACE inhibitors.
      The angiographic and clinical restenosis rates were not significantly different
      between the group treated with ACE inhibitors and the group not receiving ACE
      inhibitors (p = 0.55). Continuous measures of restenosis, minimal lumen diameter,
      diameter stenosis, late lumen loss, and loss index were also similar in both
      groups (p > or = 0.55). In addition, one-year survival free of myocardial
      infarction was not significantly different between the two groups (p = 0.27).
      CONCLUSIONS: In contrast to previous reports, our study provides evidence that
      patients carrying the DD genotype are not exposed to an increased risk of
      restenosis after stent placement when treated with ACE inhibitors.

PMID- 12798566
TI  - The race for ACE: a simple answer to the controversial puzzle of angiotensin
      converting enzyme (ACE) polymorphisms.

PMID- 12798567
TI  - Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach
      for myocardial cell transplantation.
AB  - OBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell
      introduction using the coronary venous system for direct myocardial access and
      cell delivery. BACKGROUND: Direct myocardial cell repopulation has been proposed
      as a potential method to treat heart failure. METHODS: We harvested bone marrow
      from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells,
      labeled them with the gene for green fluorescence protein, expanded them in
      culture, and resuspended them in a collagen hydrogel. Working through the
      coronary sinus, a specialized catheter system was easily delivered to the
      anterior interventricular coronary vein. The composite catheter system
      (TransAccess) incorporates a phased-array ultrasound tip for guidance and a
      sheathed, extendable nitinol needle for transvascular myocardial access. A
      microinfusion (IntraLume) catheter was advanced through the needle, deep into
      remote myocardium, and the autologous cell-hydrogel suspension was injected into
      normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1
      control/collagen biogel only), and 28 (n = 2), and the hearts were excised and
      examined. RESULTS: We gained widespread intramyocardial access to the anterior,
      lateral, septal, apical, and inferior walls from the anterior interventicular
      coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other
      procedural complications occurred. Gross inspection demonstrated no evidence of
      myocardial perforation, and biogel/black tissue dye was well localized to sites
      corresponding to fluoroscopic landmarks for delivery. Histologic analysis
      demonstrated needle and microcatheter tracts and accurate cell-biogel delivery.
      CONCLUSIONS: Percutaneous intramyocardial access is safe and feasible by a
      transvenous approach through the coronary venous system. The swine offers an
      opportunity to refine approaches used for cellular cardiomyoplasty.

PMID- 12798568
TI  - Hepatic lipase mutations,elevated high-density lipoprotein cholesterol, and
      increased risk of ischemic heart disease: the Copenhagen City Heart Study.
AB  - OBJECTIVES: We investigated associations between single nucleotide polymorphisms
      (SNPs) in the hepatic lipase promoter, levels of high-density lipoprotein (HDL),
      and risk of ischemic heart disease (IHD). Our primary hypothesis was that these
      SNPs associate with IHD after adjustment for HDL levels. BACKGROUND: Hepatic
      lipase influences HDL metabolism, and may thus affect reverse cholesterol
      transport and consequently risk of IHD. METHODS: We genotyped 9,121 white
      subjects aged 20 to 93 years from the Copenhagen City Heart Study, 456 of whom
      had incident IHD, as well as 921 Danish patients with IHD for the -216, -480, and
      -729 SNPs in the hepatic lipase promoter. RESULTS: Frequencies of wild-type,
      triple heterozygotes, and triple mutation homozygotes in the general population
      were 61%, 33%, and 5%, respectively. Compared with wild-type, HDL cholesterol
      levels were 4% (0.06 mmol/l) and 10% (0.15 mmol/l) higher in heterozygotes and
      mutation homozygotes; the equivalent values for apolipoprotein A1 were 3% and 7%
      higher. In prospective and case-control studies, mutation homozygotes versus wild
      type had relative risk (RR) and odds ratio (OR) for IHD of 1.5 (95% confidence
      interval [CI]: 1.0 to 2.2) and 1.4 (CI: 1.1 to 1.9) when adjusted for age,
      gender, and HDL cholesterol. In individuals with the epsilon43 apolipoprotein E
      genotype, RR and OR for IHD in mutation homozygotes versus wild-type was 2.9 (CI:
      1.5 to 5.6) and 2.0 (CI: 1.2 to 3.2). CONCLUSIONS: Hepatic lipase promoter SNPs
      are associated with increased HDL cholesterol and, paradoxically, an increased
      risk of IHD after adjustment for HDL cholesterol, and particularly in individuals
      with apolipoprotein E epsilon43 genotype. Implications are that increased HDL
      levels may in certain situations be not protective, but rather associated with
      increased IHD risk.

PMID- 12798569
TI  - Common genetic variation of the cholesteryl ester transfer protein gene strongly
      predicts future cardiovascular death in patients with coronary artery disease.
AB  - OBJECTIVES: We sought to evaluate the association between cholesteryl ester
      transfer protein (CETP) genotypes and the risk of future cardiovascular mortality
      in patients with coronary artery disease (CAD). BACKGROUND: Polymorphisms of the
      CETP gene influence CETP activity and high-density lipoprotein (HDL) cholesterol
      concentration and might affect the long-term prognosis and response to statin
      therapy in patients with CAD. METHODS: We used serum samples and deoxyribonucleic
      acid collected at baseline from a prospective cohort of 1,211 patients with CAD
      prospectively followed up (median follow-up of 4.1 years), 82 of whom experienced
      a fatal cardiovascular event. The CETP/C-629A and I405V polymorphisms, CETP
      activity, and HDL cholesterol were determined. RESULTS: Patients carrying the 
      629A allele had significantly lower CETP activity and higher HDL cholesterol
      levels. There was a significant association between this polymorphism and the
      risk of future cardiovascular death. Mortality decreased from 10.8% in CC
      homozygotes to 4.6% in CA heterozygotes and 4.0% in AA homozygotes (p < 0.0001).
      This association was independent of potential confounders, particularly HDL
      cholesterol and CETP activity levels. The clinical benefit of statin therapy was
      restricted to CC homozygotes, in whom cardiovascular mortality was divided by
      half (p = 0.01 for treatment x genotype interaction). Similar trends were
      observed with the CETP/I405V polymorphism, but these effects seemed to be mainly
      the consequence of linkage disequilibrium with the CETP/C-629A polymorphism.
      CONCLUSIONS: In patients with CAD, the CETP/-629A allele had a strong protective
      effect on future mortality from cardiovascular causes, independent of its role on
      HDL cholesterol and CETP activity levels. Additionally, this common polymorphism
      appeared to predict which patients with CAD will experience a survival benefit
      from statin therapy.

PMID- 12798570
TI  - Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein,
      intermediate phenotypes, and coronary risk: do they add up yet?

PMID- 12798571
TI  - Preserved endothelial function after long-term eccentric isosorbide mononitrate
      despite moderate nitrate tolerance.
AB  - OBJECTIVES: We sought to investigate the effects of orally administered, long
      term, eccentric isosorbide mononitrate (ISMN) on endothelial function.
      BACKGROUND: Previous studies have shown that nitrate tolerance induced by
      continuous transdermal glyceryl trinitrate (GTN) is associated with increased
      vascular superoxide production and endothelial dysfunction. In contrast, it is
      unclear whether vascular superoxide increases during eccentric administration of
      oral nitrates, which is a widely used therapeutic dosing regimen. METHODS: New
      Zealand White rabbits were randomly classified into three groups (n = 10, each)
      that received either placebo, ISMN at 2 mg/kg body weight per day (ISMN-2), or
      ISMN at 200 mg/kg body weight per day (ISMN-200) in an eccentric, twice-daily
      scheme for four months. Animals were sacrificed 3 h after application of the last
      ISMN dose. RESULTS: The continuously present, lowest ISMN plasma levels (ng/ml)
      were 4.8 +/- 0.2 in ISMN-2 and 14.5 +/- 4 in ISMN-200 (p = 0.026). Treatment with
      ISMN had no effect on aortic reactivity to phenylephrine, acetylcholine, or the
      nitric oxide (NO) donor S-nitroso-N-acetyl-D,L-penicillamine, while the half
      maximal effective concentration of ISMN (EC(50)-value in -logM) was shifted from
      5.23 +/- 0.03 (placebo) to 4.69 +/- 0.04 (ISMN-200) (p < 0.0001 by analysis of
      variance). This moderate in vivo nitrate tolerance was not associated with
      increased aortic superoxide production (5 micromol/l lucigenin). The cumulative
      (20-min) lucigenin signals (cpm/mg) were 211 +/- 34 (ISMN-200) and 230 +/- 22
      (placebo) (p = 0.415). CONCLUSIONS: Long-term treatment with high-dose, eccentric
      ISMN does not increase vascular superoxide production and/or impair endothelium
      dependent vasorelaxation, despite the development of moderate nitrate tolerance.
      Thus, it is unlikely that long-term anti-ischemic treatment with ISMN aggravates
      endothelial dysfunction in coronary artery disease.

PMID- 12798572
TI  - Amelioration of nitrate tolerance: matching strategies with mechanisms.

PMID- 12798573
TI  - Troponin as a risk factor for mortality in critically ill patients without acute
      coronary syndromes.
AB  - OBJECTIVES: We sought to assess the mechanism and prognostic value of elevated
      troponins in patients without acute coronary syndromes (ACS). BACKGROUND: Cardiac
      troponins are used as specific markers for the diagnosis of ACS. Recent studies
      reported a considerable number of critically ill patients without ACS as being
      troponin-positive, especially patients with sepsis, pulmonary embolism, renal
      failure, and stroke. METHODS: We analyzed 58 consecutive, critically ill patients
      admitted for reasons other than ACS, according to their troponin status. Thirty
      day mortality, left ventricular ejection fraction (LVEF), and a panel of
      inflammatory cytokines were compared between troponin-positive and troponin
      negative patients. Relevant coronary artery disease was excluded either by stress
      echocardiography or autopsy. RESULTS: Of the 58 critically ill patients, 32 (55%)
      without evidence of ACS were troponin-positive. Positive troponin levels were
      associated with higher mortality (22.4% vs. 5.2%, p < 0.018) and a lower LVEF (p
      = 0.0006). Troponin-positive patients had significantly higher median levels of
      tumor necrosis factor (TNF)-alpha, its soluble receptor, and interleukin (IL)-6.
      A subgroup of 10 aplastic patients was troponin-negative at study entry. Three
      became troponin-positive during leukocyte recovery and subsequently died, whereas
      all the others stayed troponin-negative and survived. Flow-limiting coronary
      artery disease was not demonstrable at autopsy or stress echocardiography in 72%
      of troponin-positive patients. CONCLUSIONS: Elevated troponin is a mortality risk
      factor for medical intensive care patients admitted for reasons other than ACS.
      It is associated with decreased left ventricular function and higher levels of
      TNF-alpha and IL-6.

PMID- 12798574
TI  - Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure
      with reduced or preserved ejection fraction. Results from the Breathing Not
      Properly Multinational Study.
AB  - OBJECTIVES: This study examines B-type natriuretic peptide (BNP) levels in
      patients with systolic versus non-systolic dysfunction presenting with shortness
      of breath. BACKGROUND: Preserved systolic function is increasingly common in
      patients presenting with symptoms of congestive heart failure (CHF) but is still
      difficult to diagnose. METHODS: The Breathing Not Properly Multinational Study
      was a seven-center, prospective study of 1,586 patients who presented with acute
      dyspnea and had BNP measured upon arrival. A subset of 452 patients with a final
      adjudicated diagnosis of CHF who underwent echocardiography within 30 days of
      their visit to the emergency department (ED) were evaluated. An ejection fraction
      of greater than 45% was defined as non-systolic CHF. RESULTS: Of the 452 patients
      with a final diagnosis of CHF, 165 (36.5%) had preserved left ventricular
      function on echocardiography, whereas 287 (63.5%) had systolic dysfunction.
      Patients with non-systolic heart failure (NS-CHF) had significantly lower BNP
      levels than those with systolic heart failure (S-CHF) (413 pg/ml vs. 821 pg/ml, p
      < 0.001). As the severity of heart failure worsened by New York Heart Association
      class, the percentage of S-CHF increased, whereas the percentage of NS-CHF
      decreased. When patients with NS-CHF were compared with patients without CHF (n =
      770), a BNP value of 100 pg/ml had a sensitivity of 86%, a negative predictive
      value of 96%, and an accuracy of 75% for detecting abnormal diastolic
      dysfunction. Using Logistic regression to differentiate S-CHF from NS-CHF, BNP
      entered first as the strongest predictor followed by oxygen saturation, history
      of myocardial infarction, and heart rate. CONCLUSIONS: We conclude that NS-CHF is
      common in the setting of the ED and that differentiating NS-CHF from S-CHF is
      difficult in this setting using traditional parameters. Whereas BNP add modest
      discriminatory value in differentiating NS-CHF from S-CHF, its major role is
      still the separation of patients with CHF from those without CHF.

PMID- 12798575
TI  - Natriuretic peptide measurements for the diagnosis of "nonsystolic" heart
      failure: good news and bad.

PMID- 12798576
TI  - Association of albuminuria with systolic and diastolic left ventricular
      dysfunction in type 2 diabetes: the Strong Heart Study.
AB  - OBJECTIVES: We sought to compare systolic and diastolic function in American
      Indians with diabetes mellitus (DM) based on albuminuria status. BACKGROUND:
      Albuminuria has been shown to predict cardiovascular disease (CVD) in populations
      with DM. However, the mechanism of the association of albuminuria and CVD is
      unclear. METHODS: We compared echo-derived indices of left ventricular (LV)
      systolic and diastolic function in three groups of American Indians with DM based
      on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II =
      microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g).
      RESULTS: Group II and III were slightly older than Group I with no significant
      gender difference between groups. Systolic blood pressure increased and body mass
      index decreased from Group I to Group III. Left ventricular systolic function was
      lower in the groups with albuminuria with step-wise decreases in ejection
      fraction and stress-corrected midwall shortening (MWS) from Group I to Group III.
      Similar findings were noted in diastolic LV filling with lower mitral E/A ratios
      and longer deceleration times in groups with albuminuria. The proportion of
      participants with abnormal MWS and abnormal LV diastolic relaxation showed step
      wise increases from no albuminuria to macroalbuminuria. In multivariate analysis,
      albuminuria status remained independently associated with both systolic and
      diastolic dysfunction after adjusting for age, gender, body mass index, systolic
      blood pressure, duration of diabetes, coronary artery disease, and LV mass.
      CONCLUSIONS: Albuminuria is independently associated with LV systolic and
      diastolic dysfunction in type 2 DM; this may explain in part the relationship of
      albuminuria to increased cardiovascular (CV) events in the DM population.
      Screening for albuminuria identifies individuals with high CV risk and possible
      cardiac dysfunction.

PMID- 12798577
TI  - Development of circulatory-renal limitations to angiotensin-converting enzyme
      inhibitors identifies patients with severe heart failure and early mortality.
AB  - OBJECTIVES: This study examined the hypothesis that patients who develop
      angiotensin-converting enzyme inhibitor intolerance attributable to circulatory
      renal limitations (CRLimit) have more severe underlying disease and worse
      outcome. BACKGROUND: Although the renin-angiotensin system contributes to the
      progression of heart failure (HF), it also supports the failing circulation.
      Patients with the most severe disease may not tolerate inhibition of this system.
      METHODS: Consecutive inpatient admissions to the cardiomyopathy service of the
      Brigham and Women's Hospital between 2000 and 2002 were reviewed retrospectively
      for initial profiles, discharge medications, and documented reasons for
      discontinuation of angiotensin-converting enzyme inhibitors. Outcomes of death
      and transplantation were determined. RESULTS: Of the 259 patients, 86 were not on
      an angiotensin-converting enzyme inhibitor at discharge. Circulatory-renal
      limitations of symptomatic hypotension, progressive renal dysfunction, or
      hyperkalemia were documented in 60 patients (23%); other adverse effects,
      including cough, in 24 patients; and absent reasons in 2 patients. Compared with
      patients on angiotensin-converting enzyme inhibitors, patients with CRLimit were
      older (60 vs. 55 years; p = 0.006), with longer history of HF (5 vs. 2 years; p =
      0.009), lower systolic blood pressure (104 vs. 110 mm Hg; p = 0.05), lower sodium
      (135 vs. 138 mEql/l; p = 0.002), and higher initial creatinine (2.5 vs. 1.2
      mg/dl; p = 0.0001). Mortality was 57% in patients with CRLimit and 22% in the
      patients on angiotensin-converting enzyme inhibitors during a median 8.5-month
      follow-up (p = 0.0001). CONCLUSIONS: Development of CRLimit to angiotensin
      converting enzyme inhibitor intolerance identifies patients with severe disease
      who are likely to die during the next year. New treatment strategies should be
      targeted to this population.

PMID- 12798579
TI  - Inside or out? Another option for incessant ventricular tachycardia.

PMID- 12798578
TI  - Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in
      incessant ventricular tachycardia.
AB  - OBJECTIVES: The purpose of this study was to analyze the feasibility, efficacy,
      and safety of epicardial radiofrequency (RF) ablation in patients with incessant
      ventricular tachycardia (VT). BACKGROUND: Management of patients with incessant
      VT is a difficult clinical problem. Drugs and RF catheter ablation are not always
      effective. A nonsurgical transthoracic epicardial RF ablation can be an
      alternative in patients refractory to conventional therapy. METHODS: Epicardial
      RF ablation was performed in 10 patients who presented with incessant VT despite
      the use of two or more intravenous antiarrhythmic drugs. RESULTS: In eight
      patients, endocardial ablation (EdA) failed to control the tachycardia. In the
      remaining two patients, epicardial ablation (EpA) was first attempted because of
      left ventricular thrombus and severe artery disease, respectively. Eight patients
      had a diagnosis of coronary artery disease with healed myocardial infarction. One
      patient had dilated cardiomyopathy, and one patient had idiopathic, incessant VT.
      In patients with structural heart disease, the mean ejection fraction was 0.28 +/
      0.10%. Four patients previously received an implantable defibrillator. The EpA
      effectively terminated the incessant tachycardia in eight patients, which
      represents a success rate of 80%. In them, after a follow-up of 18 +/- 18 months,
      a single episode of a different VT was documented in one patient. No significant
      complications occurred related to the procedure. CONCLUSIONS: In patients with
      incessant VT despite the use of drugs or standard EdA, the epicardial approach
      was very effective and should be considered as an alternative in this life
      threatening situation.

PMID- 12798580
TI  - Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during
      right ventricular outflow tract ventricular tachycardia.
AB  - OBJECTIVES: The purpose of this study was to objectively quantify the similarity
      of 12-lead electrocardiogram (ECG) waveforms using two quantitative metrics, the
      correlation coefficient (CORR) and the mean absolute deviation (MAD). BACKGROUND:
      Comparison of the 12-lead ECG morphology between ventricular tachycardia (VT) and
      a pace-map is frequently performed; however, there are no objective criteria for
      quantifying the similarity between two waveform morphologies. METHODS: During
      ablation of right ventricular outflow tract (RVOT) VT, 12-lead ECG pace-maps were
      acquired from three superior septal sites, three superior free wall sites, and
      before each ablation attempt in 15 patients. The 12-lead ECG waveforms of the
      clinical tachycardia and pace-maps were compared using both MAD and CORR at each
      site. RESULTS: The MAD scores were lower (i.e., more closely matched) for septal
      compared with free wall sites (15.9 +/- 5.3% vs. 25.3 +/- 10.2%; p < 0.001).
      Successful ablation sites had a significantly lower MAD score compared with
      unsuccessful sites (9.5 +/- 2.8% vs. 13.3 +/- 5.6%; p = 0.01), whereas there was
      only a trend toward a higher CORR for successful ablation sites (98.2 +/- 1.2%
      vs. 96 +/- 4.7%; p = 0.07). A MAD score < or =12% was 93% sensitive and 75%
      specific for identifying a successful ablation site. There was an inverse
      correlation between MAD score and distance from the site of VT origin (r = 0.63,
      p < 0.001). CONCLUSIONS: A MAD score >12% between RVOT VT and a pace-map at any
      site suggests sufficient dissimilarity to dissuade ablation at that site. The MAD
      score can be used to standardize 12-lead ECG waveform morphology comparisons
      among different laboratories, and may be useful for guiding ablation of VT.

PMID- 12798581
TI  - Do airport metal detectors interfere with implantable pacemakers or cardioverter
      defibrillators?
AB  - OBJECTIVES: The aim of this study was to determine whether airport metal detector
      gates (AMDGs) interfere with pacemakers (PMs) or implantable cardioverter
      defibrillators (ICDs). BACKGROUND: It is currently unknown whether AMDGs
      interfere with implanted PMs or ICDs. METHODS: A total of 348 consecutive
      patients (200 PM and 148 ICD recipients) have been tested for the occurrence of
      electromagnetic interference (EMI) within the electromagnetic field of a
      worldwide-used airport metal detector. RESULTS: No interference, such as pacing
      or sensing abnormalities, was observed in any of the 200 PM and 148 ICD patients;
      also no reprogramming occurred. CONCLUSIONS: In vivo testing of PM and ICD
      systems showed no EMI with a standard AMDG. Clinically relevant interactions with
      implanted PMs or ICDs seem unlikely.

PMID- 12798582
TI  - Quantitative assessment of coronary stenosis by harmonic power Doppler with a
      simple pulsing sequence and vasodilator stress in patients.
AB  - OBJECTIVES: We examined whether myocardial contrast echocardiography (MCE) with
      harmonic power Doppler (HPD) employing a simple ultrasound pulsing sequence
      enables estimation of the severity of coronary artery stenosis in patients.
      BACKGROUND: Contrast intensity (CI) during MCE with intravenous microbubble
      infusion is dependent on the myocardial blood flow velocity (MBFV) and pulsing
      interval (PI). METHODS: Based on an in vitro experiment, we devised the MBFV
      index calculated as the reciprocal of the magnitude of CI decay produced by
      abrupt PI shortening during intermittent imaging. In 68 coronary artery
      territories from 49 patients, myocardial HPD images were acquired during
      intravenous infusion of Levovist, while the long PI with 1:10
      electrocardiographic gating was shortened to 1:1, both at baseline and during
      adenosine triphosphate infusion. The MBFV index in each coronary territory and
      MBFV reserve as the ratio between hyperemia and baseline were compared with the
      severity of corresponding coronary artery stenosis assessed by quantitative
      coronary angiography (QCA) or by pressure guide wire as the fractional flow
      reserve (FFR). RESULTS: Both the MCE-derived MBFV index during hyperemia and MBFV
      reserve exhibited significant negative correlations with the QCA-derived stenosis
      severity (r = -0.56 and r = -0.64, respectively). The MBFV reserve positively
      correlated with FFR (r = 0.89). By combining the cutoff values of the MBFV index
      during hyperemia and MBFV reserve, > or =75% of stenoses defined by QCA were
      determined, with a sensitivity of 77.3%, specificity of 93.4%, and accuracy of
      88.3%. CONCLUSIONS: Shortening of PI during intravenous MCE with intermittent HPD
      imaging under vasodilator stress enables assessment of coronary artery stenoses
      in patients.

PMID- 12798583
TI  - The relative roles of transthoracic compared with transesophageal
      echocardiography in children with suspected infective endocarditis.
AB  - OBJECTIVES: The study evaluated the additional benefit of transesophageal
      echocardiography (TEE) versus transthoracic echocardiography (TTE) in pediatric
      cases with suspected bacterial endocarditis. BACKGROUND: In adult patients, TTE
      has a lower sensitivity and specificity than TEE for the detection of vegetations
      or aortic root abscess formation. Few data are available about the relative
      benefits of TEE over TTE in the pediatric age group. METHODS: Patients were
      included if they had positive blood cultures for typical microorganisms and had a
      TTE and TEE within 14 days of each other. The patients had to meet the Duke
      criteria for a positive diagnosis of bacterial endocarditis. The TTE and TEE data
      were analyzed using the McNemar test for the significance of change. RESULTS:
      Twenty-one patients fulfilled the criteria, at a median age of 9.5 years.
      Congenital heart disease was present in 13 patients; 4 patients were previously
      healthy and 4 patients had other medical problems. Nine patients had surgical
      confirmation of bacterial endocarditis. Fifteen patients had a positive cardiac
      finding, with 12 vegetations, 2 vegetations plus aortic root abscess, and 1
      isolated abscess. There was excellent agreement between TTE and TEE in those
      cases with positive cardiac findings, with a p = 0.32, kappa 0.89. Using positive
      TEE cardiac findings as the gold standard, the sensitivity for TTE was 86% for
      all 15 events and 93% for the detection of a vegetation. CONCLUSIONS: In
      pediatric cases, TTE has a high degree of sensitivity for the detection of
      supportive evidence of endocarditis, and TEE should be reserved for patients with
      a poor transthoracic window.

PMID- 12798584
TI  - Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations
      with atrial septal defect and hypoplastic left heart syndrome.
AB  - OBJECTIVES: We sought to examine the importance of mutations in the cardiac
      transcription factor gene NKX2-5 in patients with an atrial septal defect (ASD),
      patent foramen ovale (PFO), or hypoplastic left heart syndrome (HLHS).
      BACKGROUND: Mutations in NKX2-5 have been found in families showing secundum ASD
      and atrioventricular (AV) conduction block and in some individuals with tetralogy
      of Fallot. The prevalence of NKX2-5 mutations in sporadic cases of ASD/PFO and
      other forms of congenital heart disease is unknown. METHODS: A cohort of 146
      individuals with secundum ASD, PFO complicated by paradoxical embolism, or HLHS
      were evaluated. Patients with ASD or PFO were ascertained irrespective of family
      history or associated cardiac abnormalities. The coding region of the NKX2-5
      locus was amplified by polymerase chain reaction and sequenced. RESULTS: Among
      102 ASD and 25 PFO patients screened, 13 patients (10%) had a positive family
      history and 5 patients (4%) had AV conduction block. We found one previously
      documented NKX2-5 missense mutation, T178M, in members of a family with ASD
      without AV conduction block. One NKX2-5 mutation-positive child from this family
      had HLHS, although no mutations were subsequently found in 18 patients with
      sporadic or familial HLHS. In a second ASD family without AV conduction block, we
      found a missense change, E21Q, previously reported as pathogenic. Because this
      change did not segregate with disease status, we propose that it is a non-disease
      causing polymorphism. CONCLUSIONS: Our findings suggest that NKX2-5 mutations are
      a relatively infrequent cause of sporadic ASD and HLHS. Screening for NKX2-5
      mutations may be warranted in individuals with ASD and a positive family history,
      irrespective of the presence or absence of AV conduction block.

PMID- 12798585
TI  - Effects of aging on cardiovascular responses to parasympathetic withdrawal.
AB  - OBJECTIVES: The study was done to determine whether the effects of
      parasympathetic withdrawal on heart rate, blood pressure (BP), and systolic and
      diastolic function are altered with normal aging. BACKGROUND: Cardiac responses
      to beta-adrenergic sympathetic stimulation decline with aging as does the heart
      rate response to parasympathetic withdrawal, but the extent to which other
      responses to parasympathetic withdrawal decrease is less clear. METHODS: Heart
      rate, BP, systolic function, and diastolic filling responses to parasympathetic
      withdrawal induced by atropine (0.02 mg/kg) were compared in 50 healthy subjects,
      28 older (ages 65 to 80 years, mean 70 years; 18 females all on estrogen) and 22
      young (age 18 to 32 years, mean 26 years; 12 females) subjects, using
      radionuclide angiography. RESULTS: Parasympathetic withdrawal in the older group
      caused less of an increase in heart rate (+33 vs. +48 beats/min), cardiac index
      (+0.6 vs. +1.5 l/m(2)), systolic blood pressure (-1 vs. +7 mm Hg), and early
      diastolic filling rate (+1.7 vs. +2.4 end-diastolic volumes/s) (all p < or =
      0.01). At similar declines in the diastolic filling period, end-diastolic volume
      index (EDVI) fell substantially more in the older group (-11.6 vs. -2.4 ml/m(2),
      p < 0.001). The only gender difference was in diastolic filling rate, which was
      similar in the young males and females, but significantly less in older males
      than in older females. CONCLUSIONS: The responses to parasympathetic withdrawal
      as well as sympathetic stimulation decline with aging, and both contribute to the
      reduced cardiovascular responses to stress with advancing age.

PMID- 12798586
TI  - 17-beta-estradiol increases cardiac remodeling and mortality in mice with
      myocardial infarction.
AB  - OBJECTIVES: This study was designed to examine the effects of estrogen
      replacement on infarct size, ventricular remodeling, and mortality after
      myocardial infarction (MI) in mice. BACKGROUND: Observational and clinical
      studies suggest that the cardiovascular effects of hormone replacement therapy
      can differ depending on the patient population studied. No prospective studies
      have examined the effect of estrogen on outcomes following MI. We now examine the
      effects of estrogen replacement on infarct size, ventricular remodeling, and
      mortality after MI in mice. METHODS: Myocardial infarction was induced by left
      coronary artery ligation in ovariectomized female mice treated with 17-beta
      estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic
      function was assessed, animals were euthanized, and infarct size was determined.
      RESULTS: 17-beta-estradiol-treated mice had smaller infarcts than placebo-treated
      animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p <
      0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the
      terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50%
      reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite
      having smaller infarcts, however, left ventricular mass increased more in the E2
      treated animals (16% greater; p < 0.01). Left ventricular weight was positively
      correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p =
      0.0001). 17-beta-estradiol treatment also significantly increased mortality in
      the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2
      to 5.3). CONCLUSIONS: Estrogen replacement therapy reduces infarct size and
      cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular
      remodeling and mortality. Further studies will be necessary to elucidate the
      mechanisms underlying the complex effects of estrogen observed in the present
      study.

PMID- 12798587
TI  - Early outcome after sirolimus-eluting stent implantation in patients with acute
      coronary syndromes: insights from the Rapamycin-Eluting Stent Evaluated At
      Rotterdam Cardiology Hospital (RESEARCH) registry.
AB  - OBJECTIVES: This study evaluated the early outcomes of patients with acute
      coronary syndromes (ACS) treated with sirolimus-eluting stents (SES). BACKGROUND:
      The safety of SES implantation in patients with a high risk for early thrombotic
      complications is currently unknown. METHODS: Sirolimus-eluting stents have been
      utilized as the device of choice for all percutaneous procedures in our
      institution, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam
      Cardiology Hospital (RESEARCH) registry. After four months of enrollment, 198
      patients with ACS had been treated exclusively with SES (64% of those treated in
      the period) and were compared with a control group composed of 301 consecutive
      patients treated with bare stents in the same time period immediately before this
      study. The incidence of major adverse cardiac events (MACE) during the first
      month was evaluated (death, nonfatal myocardial infarction [MI], or re
      intervention). RESULTS: Compared with control patients, patients treated with SES
      had more primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting
      (13% vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less
      glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The 30-day
      MACE rate was similar between both groups (SES 6.1% vs. control patients 6.6%; p
      = 0.8), with most complications occurring during the first week. Stent thrombosis
      occurred in 0.5% of SES patients and in 1.7% of control patients (p = 0.4). In
      multivariate analysis, SES utilization did not influence the incidence of MACE
      (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p = 0.97). CONCLUSIONS:
      Sirolimus-eluting stent implantation for patients with ACS is safe, with early
      outcomes comparable with bare metal stents.

PMID- 12798588
TI  - Clinical investigation...an impending crisis?

PMID- 12798589
TI  - What is the mechanism of abnormal blood pressure response on exercise in
      hypertrophic cardiomyopathy?

PMID- 12798591
TI  - Beneficial effects of simvastatin and pravastatin on cardiac allograft rejection
      and survival.

PMID- 12798593
TI  - Growth factors: can they promote neurogenesis?
AB  - Cortical development is a complex process in which extrinsic and intrinsic
      factors modulate the sequential generation of neurons and glia. Following
      successive rounds of division, precursors become determined along a neuronal or
      glial lineage prior to cell cycle exit and differentiation. Although the
      influence of growth factors in cell fate specification is not new, until recently
      little was known about the signaling pathways by which they regulate neuronal
      differentiation. Menard and colleagues have examined this issue and have
      demonstrated a role for the MEK-C/EBP (mitogen-activated-protein-kinase kinase
      and CCAAT/enhancer-binding protein) pathway in the promotion of growth factor
      mediated neurogenesis.

PMID- 12798594
TI  - A memory GAP.
AB  - Pavlovian conditioning of the response to fear has provided an important model
      for memory formation in mammals. Several studies have begun to identify the key
      signal-transduction components that provide the molecular basis for this complex
      neural process. A recent report has revealed that the Rho GTPase and its
      regulator p190 Rho-GTPase-activating protein (p190 RhoGAP) also play an important
      regulatory role in fear memory formation.

PMID- 12798596
TI  - Binocular rivalry and perceptual multi-stability.
AB  - When different images are presented to the two eyes, binocular rivalry can occur 
      that is, perceptual alternations between the two monocular images (bi-stability)
      or between more than two percepts comprised of complementary portions of the two
      images (multi-stability). A recent paper reports important findings about the
      dynamics of multi-stable alternations in binocular rivalry.

PMID- 12798597
TI  - Blood on the tracks: a simple twist of fate?
AB  - Recent studies suggest that non-neural cells can generate neurons in mice and
      humans. There is no lack of excitement about these results: they challenge our
      view of cellular differentiation and the prospect of being able to generate
      neurons from, for example, blood is very attractive. But is it too good to be
      true?

PMID- 12798598
TI  - Protective autoimmunity against the enemy within: fighting glutamate toxicity.
AB  - Glutamate, a key neurotransmitter, is pivotal to CNS function. Alterations in its
      concentration can be dangerous, as seen for example in acute injuries of the CNS,
      chronic neurodegenerative disorders and mental disorders. Its homeostasis is
      attributed to the efficient removal of glutamate from the extracellular milieu by
      reuptake via local transport mechanisms. Our recent studies suggest that
      glutamate, either directly or indirectly, elicits a purposeful systemic T-cell
      mediated immune response directed against immunodominant self-antigens that
      reside at the site of glutamate-induced damage. We suggest that the harnessed
      autoimmunity (which we have termed 'protective autoimmunity') helps the resident
      microglia in their dual function as antigen-presenting cells (serving the immune
      system) and as cells that clear the damaged site of potentially harmful material
      (serving the nervous system). The interplay between glutamate and an adaptive
      immune response illustrates the bidirectional dialog between the immune and
      nervous systems, under both physiological and pathological conditions. These
      results point to the possible development of a therapeutic vaccination with self
      antigens, or with antigens cross-reactive with self-antigens, as a way to augment
      autoimmunity without inducing an autoimmune disease, thus providing a safe method
      of limiting degeneration. This approach, which boosts a physiological mechanism
      for the regulation of glutamate, and possibly also that of other self-compounds,
      might prove to be a feasible strategy for therapeutic protection against
      glutamate-associated neurodegenerative or mental disorders.

PMID- 12798599
TI  - A new view of pain as a homeostatic emotion.
AB  - Pain is conventionally viewed as a pattern of convergent activity within the
      somatosensory system that represents the exteroceptive sense of touch.
      Accumulating functional, anatomical and imaging findings indicate that pain is
      generated by specific sensory channels that ascend in a central homeostatic
      afferent pathway. Phylogenetically new thalamocortical projections in primates
      provide a sensory image of the physiological condition of the body and, in
      addition, direct activation of limbic motor cortex. These findings indicate that
      the human feeling of pain is both a distinct sensation and a motivation - that
      is, a specific emotion that reflects homeostatic behavioral drive, similar to
      temperature, itch, hunger and thirst.

PMID- 12798600
TI  - Leaning to the left: laterality in the zebrafish forebrain.
AB  - How the brain becomes lateralized is poorly understood. By contrast, much is
      known about molecular cues that specify the left-right axis of the body,
      fashioning the asymmetric morphology and positioning of the visceral organs. In
      zebrafish, the Nodal signaling pathway functions in visceral asymmetry and also
      in the embryonic brain, to bias laterality of the epithalamus. Formation of an
      asymmetric pineal complex differentially influences adjacent diencephalic nuclei,
      the left and right habenulae, which acquire distinctive molecular and cellular
      features. Results from the genetically tractable zebrafish system provide a
      promising entry point for exploring how left-right biases are established and
      propagated in the developing vertebrate brain.

PMID- 12798601
TI  - Strange vision: ganglion cells as circadian photoreceptors.
AB  - A novel photoreceptor of the mammalian retina has recently been discovered and
      characterized. The novel cells differ radically from the classical rod and cone
      photoreceptors. They use a unique photopigment, most probably melanopsin. They
      have lower sensitivity and spatiotemporal resolution than rods or cones and they
      seem specialized to encode ambient light intensity. Most surprisingly, they are
      ganglion cells and, thus, communicate directly with the brain. These
      intrinsically photosensitive retinal ganglion cells (ipRGCs) help to synchronize
      circadian rhythms with the solar day. They also contribute to the pupillary light
      reflex and other behavioral and physiological responses to environmental
      illumination.

PMID- 12798602
TI  - Changes in behavior-related neuronal activity in the striatum during learning.
AB  - The involvement of the striatum in numerous forms of learning and memory is
      likely to be based on changes in neuronal activity when specific behavioral tasks
      are being learned. Striatal neurons show distinctive changes when animals learn
      the significance of stimuli that predict rewards and induce the preparation of
      movements. These changes resemble some of the simultaneous, learning-related
      changes in closely associated areas of the frontal cortex. The striatal changes
      might assist in adapting existing reward expectations and behaviors to novel or
      changing environmental conditions and they could contribute to the functions of
      the basal ganglia in learning, reward expectation and movement preparation.

PMID- 12798603
TI  - Brain-machine interfaces: computational demands and clinical needs meet basic
      neuroscience.
AB  - As long as 150 years ago, when Fritz and Hitzig demonstrated the electrical
      excitability of the motor cortex, scientists and fiction writers were considering
      the possibility of interfacing a machine with the human brain. Modern attempts
      have been driven by concrete technological and clinical goals. The most advanced
      of these has brought the perception of sound to thousands of deaf individuals by
      means of electrodes implanted in the cochlea. Similar attempts are underway to
      provide images to the visual cortex and to allow the brains of paralyzed patients
      to re-establish control of the external environment via recording electrodes.
      This review focuses on two challenges: (1) establishing a 'closed loop' between
      sensory input and motor output and (2) controlling neural plasticity to achieve
      the desired behavior of the brain-machine system. Meeting these challenges is the
      key to extending the impact of the brain-machine interface.

PMID- 12798604
TI  - Affordable worldwide rabies post-exposure treatment.

PMID- 12798605
TI  - Immunogenicity of recombinant HBsAg/HCV particles in mice pre-immunised with
      hepatitis B virus-specific vaccine.
AB  - Due to their spatial structure virus-like particles (VLPs) generally induce
      effective immune responses. VLPs derived from the small envelope protein (HBsAg
      S) of hepatitis B virus (HBV) comprise the HBV vaccine. Modified HBsAs-S VLPs,
      carrying the immunodominant hypervariable region (HVR1) of the hepatitis C virus
      (HCV) envelope protein E2 within the exposed 'a'-determinant region (HBsAg/HVR1
      VLPs), elicited HVR1-specific antibodies in mice. A high percentage of the human
      population is positive for anti-HBsAg antibodies (anti-HBs), either through
      vaccination or natural infection. We, therefore, determined if pre-existing anti
      HBs could influence immunisation with modified VLPs. Mice were immunised with a
      commercial HBV vaccine, monitored to ensure an anti-HBs response, then immunised
      with HBsAg/HVR1-VLPs. The resulting anti-HVR1 antibody titre was similar in mice
      with or without pre-existing anti-HBs. This suggests that HBsAg/HVR1-VLPs induce
      a primary immune response to HVR1 in anti-HBs positive mice and, hence, they may
      be used successfully in individuals already immunised with the HBV vaccine.

PMID- 12798606
TI  - Evaluation of synthetic, M type-specific peptides as antigens in a multivalent
      group A streptococcal vaccine.
AB  - The recent development of emm gene sequence-based typing methodology has allowed
      group A streptococci (GAS) M serotype prevalence data to be determined. This
      information has been used to identify the components of a multivalent M protein
      peptide vaccine that could theoretically prevent most of the GAS-mediated
      diseases in the USA. In this study, we have evaluated in mice the immunogenicity
      and protective ability of multiple synthetic, M type-specific peptides, derived
      from the N-termini of three prevalent GAS serotypes (three peptides per serotype,
      total of nine peptides). At least one peptide, representing each of the three M
      types tested, was immunogenic. Five of the nine synthetic peptides tested,
      elicited an immune response in mice, and sera raised against four of the
      peptides, all possessed functional activity as demonstrated in a bactericidal
      assay. In vivo nasopharyngeal challenge experiments were carried out with
      peptides from the M1 (peptide M1-3) and M3 (peptide M3-2) proteins induced in
      vivo immune protection by reducing intranasal carriage. Reduction in colonization
      for M1-3 and M3-2 was 90% (P=0.02) and 66% (P<0.17), respectively. A reduction in
      colonization of 67% (P=0.03) was observed for M3-2 immunized mice when M43, a
      heterologous serotype, was used as the challenge strain. These results show the
      utility of synthetic, M type-specific peptides as antigens in a multivalent GAS
      vaccine.

PMID- 12798607
TI  - Theoretic coverage of heptavalent pneumococcal conjugate vaccine in the
      prevention of community-acquired pneumonia in children in Italy.
AB  - In order to evaluate the theoretic coverage of the heptavalent conjugate vaccine
      against community-acquired pneumonia (CAP) during the first years of life, the
      anti-capsular IgG antibodies to the nine more common pneumococcal serotypes (1,
      4, 5, 6B, 9V, 14, 18C, 19F, 23F) were quantitated in 196 affected children aged 2
      5 years by means of enzyme-linked immunosorbent assays of acute and convalescent
      serum samples. Acute Streptococcus pneumoniae infection associated with the nine
      tested serotypes was diagnosed in 57 children (29.1%). Serological data indicated
      that 16.8% of CAPs were caused by serotypes included in the heptavalent conjugate
      vaccine. This study confirms the significant role of S. pneumoniae in pediatric
      CAP, and highlights the importance of pneumococcal conjugate vaccines in
      preventing it during the first years of life.

PMID- 12798608
TI  - The predicted impact of private sector MMR vaccination on the burden of
      Congenital Rubella Syndrome.
AB  - In many developing countries, Measles-Mumps-Rubella (MMR) vaccine is available
      through the private but not the public sectors, and there is no systematic
      rubella vaccination among adult women. In this paper, we extend previous modeling
      studies to demonstrate that in developing countries with a medium-high force of
      infection (200-400/1000 per year), current levels of private sector MMR coverage
      (<60%) would lead to increases in the incidence of Congenital Rubella Syndrome
      (CRS) both among unvaccinated individuals and the general population even when
      mixing between vaccinated and unvaccinated individuals is fairly minimal. Our
      findings highlight the need for countries to establish surveillance of trends in
      susceptibility to rubella and CRS incidence and perhaps introduce rubella
      vaccination among women of child-bearing age.

PMID- 12798609
TI  - Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen,
      Der p 1 for oral vaccination in mice.
AB  - Our previous studies indicated that intramuscular (i.m.) immunisation with full
      length Der p 1 cDNA induced significant humoral response to the left domain
      (approximately corresponding to amino acids 1-116) but not to the right domain
      (approximately corresponding to amino acids 117-222) of Der p 1 allergen. This
      study explored the use of chitosan-DNA nanoparticles for oral immunisation to
      induce immune responses specific to both the left and right domains of Der p 1.
      DNA constructs pDer p 1 (1-222) and pDer p 1 (114-222) were complexed with
      chitosan and delivered orally followed by an i.m. injection of pDer p 1 (1-222)
      13 weeks later. Such approach has successfully primed Th1-skewed immune responses
      against both domains of Der p 1. This strategy could be further optimised for
      more efficacious gene vaccination for full length Der p 1.

PMID- 12798610
TI  - A recombinant fowl adenovirus expressing the S1 gene of infectious bronchitis
      virus protects against challenge with infectious bronchitis virus.
AB  - The spike peplomer S1 subunit sequence from avian infectious bronchitis virus
      (IBV) Vic S strain was expressed in a plasmid under the control of the fowl
      adenovirus (FAV) major late promoter (MLP). Two recombinants were constructed in
      FAV serotype 8 (FAV 8) by inserting the expression cassette between the SnaBI and
      XbaI restriction enzyme sites (clone DA3) or between the SpeI sites (clone CA6
      20). Expression of the S1 gene in the recombinants was confirmed by reverse
      transcription-polymerase chain reaction (RT-PCR) by 20h post-infection.
      Commercial broiler chickens were orally vaccinated at day 0 or day 6 post-hatch
      and challenged at day 35 post-hatch. FAV antibody ELISA confirmed that maternal
      antibody directed against inclusion body hepatitis (serotype 8) had decayed in
      control birds and that FAV specific serum IgG responses were produced in
      vaccinated birds at the time of challenge. Further, an S1 specific antibody
      response was detected prior to challenge. Birds were challenged with either Vic S
      (serotype B) or N1/62 (serotype C) strains of IBV. The tracheas of challenged
      birds were analyzed by RT-PCR and re-isolation of virus. In birds vaccinated at
      day 6, 90-100% protection at the trachea was induced against either homologous or
      heterologous challenge. The construction of a recombinant FAV expressing S1 of
      IBV demonstrates the potential of an alternative vaccination strategy against
      IBV.

PMID- 12798611
TI  - 10 year assessment of infant hepatitis B vaccination program, in the Loyalty
      Islands (New Caledonia).
AB  - OBJECTIVES OF THE STUDY: To evaluate the decrease of hepatitis B prevalence in
      New Caledonia 10 years after the implementation of a neonatal vaccination program
      and discuss the need of any booster in preadolescents. METHOD: A survey was
      conducted in the Loyalty Islands, involving 593 children aged 8-11 years.
      Serological profiles were determined using three parameters: antibodies to core
      and surface antigens and HBs Ag. RESULTS: The vaccine coverage rate is 93 and 89%
      of the children are protected against hepatitis B. However, 8% of them did have
      contact with the virus and 1.3% are carriers. Thirty-eight percent of the
      vaccinated children had their first injection later than the age of 3 months.
      CONCLUSION: This study attests that the neonatal immunisation is accepted and
      followed. The prevalence reduction is not as great as expected, probably due to
      excess delay in primary vaccination. Hepatitis B eradication could be achieved in
      New Caledonia by starting immunisation at birth, and by implementing a global
      catch-up program among preadolescents.

PMID- 12798612
TI  - Non-responders to egg grown influenza vaccine seroconvert after booster
      immunization with MDCK cell grown vaccine.
AB  - We have investigated whether 'at risk' subjects who did not respond serologically
      during a pre-study vaccination with a commercial egg grown influenza sub-unit
      vaccine would respond to a subsequent vaccination with either a single dose of
      MDCK cell grown influenza vaccine or a standard egg grown influenza vaccine
      containing the same virus strains. We studied 48 non-responder subjects with a
      mean age 67.5, range: 34-82 years. In this non-responder group the increased
      immune response that was detected after boosting with an MDCK cell derived
      vaccine response was variable and relatively modest, except for the A/Texas
      strain in the vaccine. The proportion of subjects, with an HI titre of >/=40
      (protective antibody titre) increased from 50 to 83% (A/Texas strain), from 13 to
      25% (B/Harbin strain) and from 38 to 46% (A/Wuhan strain). In comparison a
      booster vaccination with egg-derived influenza vaccine resulted in an increase
      immune response with an HI antibody titre >/=40 for two of the three strains,
      namely from 17 to 58% for the B/Harbin strain and from 8 to 33% for the A/Wuhan
      strain.

PMID- 12798613
TI  - Intramuscular versus intradermal administration of anti-hepatitis B vaccine in
      non-cirrhotic hepatitis C patients.
AB  - Intradermal vaccination has been proposed as an alternative for the
      administration of anti-hepatitis B vaccine. Patients (n=66) with chronic viral
      hepatitis C without cirrhosis were randomised into two groups (intramuscular,
      n=38; and intradermal, n=28) for prospective immunisation with 20 microg
      recombinant vaccine, using an ultra-rapid schedule (doses at 0, 15 and 30 days).
      Sero-conversion (antibody level >/=10 mU/ml) in the intramuscular group was
      reached by 20, 40 and 72% of patients at days 15, 30 and 60 compared to 4, 8 and
      36% for the intradermal group (P=0.010 at day 60). Additionally, levels rose more
      rapidly in the intramuscular group (P=0.004). Our results do not support the use
      of intradermal route of immunisation against HBV in HCV patients.

PMID- 12798614
TI  - Growth phase of orally administered Lactobacillus strains differentially affects
      IgG1/IgG2a ratio for soluble antigens: implications for vaccine development.
AB  - Lactobacillus strains with probiotic activity are major constituents of numerous
      common food products. Due to their 'generally regarded as safe'-status (GRAS
      status), Lactobacillus strains can also be genetically engineered for use in oral
      immunotherapeutic applications, such as vaccination and T lymphocyte tolerance
      induction in autoimmune disease.In the current study, we demonstrate that the
      growth phase of orally administered individual Lactobacillus strains can
      differentially affect antigen-specific antibody subclasses IgG1 and IgG2a, which
      might reflect skewing of systemic activity of T helper cell type 2 (Th2) and T
      helper cell type 1 (Th1) pathways, respectively. Mice were orally fed different
      wild type Lactobacillus strains in log phase or stationary phase and immunized
      intraperitoneally with a T-cell dependent protein antigen. Sera were evaluated
      for the ratio of antigen-specific IgG1 and IgG2a antibodies. Stationary
      Lactobacillus murines and Lactobacillus casei cultures, but not two other
      Lactobacillus strains, evoked significantly higher IgG1/IgG2a ratios than log
      phase cultures, possibly relating to increased activity of the Th2-pathway.
      Despite normal variation in antibody responses against TNP-CGG among individual
      mice, a high correlation was found between the IgG1 and IgG2a responses of mice
      within experimental groups. This differential antibody response is likely due to
      growth phase-dependent differences in bacterial cell composition.Since
      Lactobacillus growth phase dependent skewing of antibody responses possibly
      reflecting T-cell pathways can inadvertently affect allergic and (auto)-immune
      responses, the current findings strongly caution against unidimensional views on
      the oral administration of individual Lactobacillus strains for probiotic or
      immunotherapeutic purposes, but also suggest additional possibilities for immune
      modulation.

PMID- 12798616
TI  - A subunit vaccine against the adenovirus egg-drop syndrome using part of its
      fiber protein.
AB  - In this study, the effectiveness of antibodies against the hexon, fiber or a
      fiber fragment of an avian adenovirus egg-drop syndrome (EDS), in neutralizing
      the virus was tested. The fiber protein is responsible for binding the virus to
      the target cell. The fiber fragment knob-s comprises the carboxy-terminal knob
      domain and 34 amino acids of the immediately adjacent shaft domain of the
      adenovirus fiber protein. The hexon, fiber capsid protein and knob-s were
      produced in E. coli and injected into chickens. Antibodies that were produced
      against the whole fiber protein showed some hemagglutination inhibition (HI)
      activity. Antibodies produced against the knob-s protein showed HI activity and
      serum neutralization (SN) activity similar to the positive control-whole virus
      vaccine. We assume that production of only part of the fiber enables the protein
      produced in E. coli to fold correctly. Antibodies produced against the hexon
      protein showed no SN activity. In summary, knob-s induced SN and HI antibodies
      against EDS virus at a rate similar to the whole virus and were significantly
      more efficient than the full-length fiber. The recombinant knob-s protein may be
      used as a vaccine against pathogenic adenovirus infections.

PMID- 12798615
TI  - Immunogenicity of a new Salmonella Typhi Vi polysaccharide vaccine--vax-TyVi--in
      Cuban school children and teenagers.
AB  - A randomized, controlled, double blind study was carried out in Cuban children
      and teenagers aged 9-13 years to evaluate the immunogenicity of vax-TyVi
      Salmonella Typhi Vi polysaccharide vaccine-with respect control vaccines. Serum
      samples were taken before and 21 days after the immunization, and ELISA was used
      for the determination of antibodies to Vi polysaccharide. Subjects who received
      vax-TyVi and TYPHIM Vi (Pasteur-Merieux) showed seroconversion rates of 85.61 and
      78.36%, respectively. The geometric mean titer (GMT) values for Vi antibodies
      induced after vaccination were 6.27 microg/ml (5.40-7.38 microg/ml) and 5.97
      microg/ml (5.01-7.10 microg/ml), respectively. In contrast, subjects receiving
      the tetanus toxoid vaccine showed 0% seroconversion.

PMID- 12798617
TI  - A novel multivalent human CTL peptide construct elicits robust cellular immune
      responses in HLA-A*0201 transgenic mice: implications for HTLV-1 vaccine design.
AB  - Cytotoxic T-lymphocytes are critical in the clearance of chronic viral infections
      such as HTLV-1. Peptide-based vaccines may have potential application in invoking
      antiviral CTL responses. In the development of vaccination strategies, it is
      becoming increasingly important to elicit a broad immune response against several
      epitopes simultaneously that may provide large population coverage. In the
      present study, we addressed this issue, namely the processing and presentation of
      multiple CTL epitopes simultaneously for the generation of multispecific CTL
      responses. We designed a novel multivalent peptide consisting of three HLA
      A(*)0201 restricted CTL epitopes, with intervening double arginine residues in
      tandem. These epitopes were derived from the HTLV-1 regulatory protein Tax, which
      is an attractive target for vaccine development against HTLV-1. Arginine residues
      were included to provide cleavage sites for proteasomes, to generate the intended
      MHC Class I ligands. Proteasomal digestion studies and mass spectrometry analysis
      showed cleavage of the multivalent construct to generate the individual epitopes.
      Immunization of HLA-A(*)0201 transgenic mice with this construct efficiently
      elicited cellular responses to each intended epitope in vivo, further validating
      the applicability of this approach. These data may have potential in the
      development of immunotherapeutic strategies for the treatment of HTLV-1 disease
      and in the future design of multivalent subunit peptide vaccines.

PMID- 12798618
TI  - BCG scar and positive tuberculin reaction associated with reduced child mortality
      in West Africa. A non-specific beneficial effect of BCG?
AB  - Previous studies have suggested that the bacille Calmette-Guerin (BCG) vaccine
      may have a non-specific beneficial effect on childhood survival in areas with
      high mortality. We examined whether BCG-vaccinated children with a BCG scar or a
      positive tuberculin reaction had better survival than children without such
      reactions. As part of an ongoing two-dose measles vaccine trial for which
      children were recruited at 6 months of age, we examined 1813 children for BCG
      scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for
      delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG
      vaccinated children with a BCG scar had significantly lower mortality compared
      with BCG scar-negative children, the mortality ratio in the first 12 months of
      follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive
      tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with
      tuberculin negative children. These results were unchanged by control for
      potential confounders or using different cut-off points for a tuberculin-positive
      response. Exclusion of dead children who had HIV antibodies did not modify the
      estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis
      (TB) exposure at home, the mortality ratios for having a scar and being
      tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively.
      Children positive to tetanus or diphtheria in the skin test had the same
      mortality as children not responding to these vaccine-related antigens. Thus, BCG
      scar and a positive tuberculin reaction were associated with better survival in
      early childhood in an area with high mortality. Since nothing similar was found
      for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect
      could not be explained by protection against tuberculosis, the effect of BCG
      vaccination could be due to non-specific immune-stimulation protecting against
      other infections.

PMID- 12798619
TI  - Correlation of body temperature with protection against staphylococcal
      enterotoxin B exposure and use in determining vaccine dose-schedule.
AB  - The immunoprotective potential of a recombinant vaccine against the
      incapacitating effect of aerosolized staphylococcal enterotoxin B (SEB) in
      nonhuman primates is reported. SEB belongs to a family of structurally related
      superantigens responsible for serious, life threatening pathologies. Injecting
      the recombinant SEB vaccine did not induce temperature elevation in rhesus
      monkeys, a classical symptom of toxic-shock syndrome. No temperature elevation
      was noted following injection with control tetanus toxoid. In addition to 100%
      survival, we observed a clear correlation between vaccine dose and mitigation of
      temperature elevation after a lethal SEB aerosol challenge. We conclude that the
      recombinant SEB vaccine is non-pyrogenic and that monitoring changes in body
      temperature is an important biomarker of toxic shock in a primate animal model.

PMID- 12798620
TI  - An improved Pythium insidiosum-vaccine formulation with enhanced
      immunotherapeutic properties in horses and dogs with pythiosis.
AB  - The immunotherapeutic properties of a new Pythium insidiosum-vaccine formulation
      (PIV), was evaluated in 18 horses and 6 dogs with proven pythiosis from different
      enzootic areas in the United States. All injected horses but one responded with a
      weak (=29 mm, n=3), a mild (30-90 mm, n=7) or a strong (=100 mm, n=7)
      inflammatory reactions at the site of injection. Three equines with weak or
      negative reactions at the injection site were not cured. Seven equines with
      strong reactions at their injection sites, however, were cured. Six of the eight
      horses with mild reactions were also cured. The remaining two equines responded
      at first but both relapsed and finally died of their infections. The PIV cured
      only two of the six dogs used in this study. The new PIV formulation cured 72% of
      the equines (P=0.048) and 33% of the dogs with pythiosis. Dogs with chronic
      disease (greater than two months) did not responded to immunotherapy. The finding
      of eosinophils, mast cells, IgE and precipitin IgG during pythiosis suggested
      that a T helper 2 (Th2) subset is in place during this disease. In cured horses,
      the eosinophilic reaction was substituted by lymphocytes and mononuclear
      macrophages (Th1). This and previous studies strongly support the hypothesis that
      an immune-modulation from a Th2 to a Th1 subsets may be in part responsible for
      the PIV's curative properties.

PMID- 12798621
TI  - Evaluation of novel aerosol formulations designed for mucosal vaccination against
      influenza virus.
AB  - Influenza viruses are among the most significant human pathogens, responsible for
      increased seasonal morbidity and mortality particularly in immunodepressed and
      chronically ill. Conventional vaccination with non-replicative vaccine is
      currently performed by injection. In the present study, we explore simple spray
      dried lipid formulations containing whole inactivated virus or split-subunit
      vaccine that allow aerosolization and thus, mucosal vaccination of the pulmonary
      tract. We show that by using biocompatible excipients already approved for human
      use, one could engineer microparticles that induce substantial local and systemic
      immunity subsequent to pulmonary administration. Exposure of the bronchial
      associated lymphoid tissue (BALT) to vaccine was more effective than parenteral
      or nasal administration in triggering specific immunity. Co-formulation of a
      biocompatible surfactant detergent greatly ameliorated the immune profile of
      microparticles containing a whole inactivated virus vaccine. In addition, mere
      formulation of a licensed split-subunit vaccine significantly enhanced its
      immunogenicity. Together, our data underline a simple strategy to convert
      conventional parenteral vaccination of currently available non-replicative
      vaccines against influenza virus, into one that is more effective and practical
      upon respiratory administration.

PMID- 12798622
TI  - DNA vaccination with the immunodominant tachyzoite surface antigen (SAG-1)
      protects against adult acquired Toxoplasma gondii infection but does not prevent
      maternofoetal transmission.
AB  - We examined the ability of a DNA vaccine comprising the Toxoplasma gondii
      tachyzoite immunodominant surface antigen, SAG-1, to both protect adult BALB/c
      mice against infection with the avirulent Beverly type-2 strain of T. gondii and
      also to inhibit the incidence of congenital disease. Vaccination induced an
      enhanced type-1 immune response as measured by IgG2a antibody production and
      increased splenocyte IFN-gamma production. Vaccination also limited disease
      following infection via either the oral or peritoneal routes as measured by
      mortality, pathology or brain cyst burden. While vaccination with plasmid alone
      also increased splenocyte IFN-gamma production, this afforded no protection and
      following infection mortality rates and cyst burden counts were similar in this
      group to that of non-vaccinated animals. Although, vaccination with SAG-1 DNA did
      protect against adult acquired T. gondii infection, it did not prevent
      maternofoetal transmission in previously vaccinated dams infected during
      pregnancy. The results indicate differences in the protective mechanisms
      operating between adult acquired disease and congenital transmission and have
      significant implications for future vaccine development.

PMID- 12798623
TI  - Immunogenicity of recombinant Mannheimia haemolytica serotype 1 outer membrane
      protein PlpE and augmentation of a commercial vaccine.
AB  - Mannheimia haemolytica is the major cause of severe bacterial pneumonia
      associated with shipping fever in cattle. The gene for M. haemolytica outer
      membrane protein (OMP) PlpE was cloned into the expression vector pRSETA. The
      cloned gene was then expressed in BL21(DE3)pLysS and the recombinant PlpE (rPlpE)
      was purified and used in immunological and vaccination studies. Vaccination of
      cattle with commercial M. haemolytica vaccines stimulated no significant (P>0.05)
      antibody responses to rPlpE. Recombinant PlpE in a commercial proprietary
      adjuvant was highly immunogenic when injected subcutaneously into cattle.
      Vaccination of cattle with 100 microg of rPlpE markedly enhanced resistance
      against experimental challenge with virulent M. haemolytica. Addition of 100
      microg of rPlpE to a commercial M. haemolytica vaccine, Presponse, significantly
      enhanced (P<0.05) protection afforded by the vaccine against experimental
      challenge. Addition of rPlpE to commercial M. haemolytica vaccines could greatly
      enhance vaccine efficacy.

PMID- 12798624
TI  - Epidermal powder immunization of mice and monkeys with an influenza vaccine.
AB  - Epidermal powder immunization (EPI) with an influenza vaccine and an adjuvant
      such as QS-21, LTR72, or cholera toxin elicited augmented serum and mucosal
      antibody responses in mice. Rhesus macaques, which have an immune system and skin
      structure similar to humans, were used to further evaluate the immunogenicity of
      the influenza vaccine following EPI. EPI of rhesus macaques with an influenza
      vaccine and QS-21 adjuvant elicited significantly higher serum hemagglutination
      inhibition (HI) titers than antigen alone administered by EPI or by intramuscular
      (IM) injection using a needle and syringe. In the absence of QS-21, EPI and IM
      injection elicited comparable HI titers in the monkeys. This study suggests that
      EPI is a promising technique for administering human vaccine and that QS-21
      augments the immunogenicity of co-administered influenza vaccine.

PMID- 12798625
TI  - Enhanced adjuvanticity of interleukin-2 plasmid DNA administered in
      polyethylenimine complexes.
AB  - We report here the enhanced adjuvant effect of murine interleukin-2 plasmid DNA
      (mIL-2) by complexation with a cationic polymer polyethylenimine (PEI). The mRNA
      expression of mIL-2 was observed at C2C12 cells after treatment with pVAXmIL-2 in
      PEI-complexed form, but not in naked plasmid DNA. In vivo, the plasmid DNA levels
      of mIL-2 at the administered muscle tissues were prolonged up to 14 days after
      intramuscular administration in PEI complexes. Moreover, the mRNA expression
      level in the muscle was 54-fold higher in PEI-complexed pVAXmIL-2 than in naked
      pVAXmIL-2 at 14 days after intramuscular administration. Mice were immunized on
      Days 0 and 28 by intramuscular administration of hepatitis B surface antigen
      (HBsAg) alone or with pVAXmIL-2 in naked or PEI complexes. At 8 weeks after the
      first immunization, mice coadministered with HBsAg plus pVAXmIL-2 in PEI
      complexes showed the serum IgG titer 72- and 208-fold higher as compared to those
      treated with HBsAg plus naked pVAXmIL-2 and with HBsAg alone, respectively.
      Though both HBsAg-specific IgG(1) and IgG(2a) immune responses were increased
      upon complexation of pVAXmIL-2 with PEI, IgG(2a) was more effectively induced
      relative to IgG(1). These results suggest that the complexation with PEI could be
      useful for prolonging in vivo expression of genetic cytokine adjuvants and
      enhancing their adjuvanticity for subunit vaccines.

PMID- 12798626
TI  - A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis
      longicornis; cloning and preliminary assessment of its suitability as a candidate
      for a tick vaccine.
AB  - Rapid amplification of the cDNA ends (RACE) and primers designed based on a
      conserved serpin amino acid motif (NAVYFKG) were used to clone a 1350bp cDNA
      which encodes a 378 polypeptide with high sequence similarity to several known
      serpins. We have named this gene as Haemaphysalis longicornis serpin-1 (HLS1).
      Northern blotting and reverse transcription (RT)-PCR analysis of total RNA from
      unfed or partially fed whole ticks as well as dissected tick organs revealed that
      transcription of HLS1 mRNA was induced by blood meal feeding during the slow
      feeding phase (24-48 h post-attachment) only in the tick midguts. Vaccination of
      rabbits with recombinant HLS1 (rHLS1) expressed in Escherichia coli resulted in
      43.9 and 11.2% mortality of nymph and adult ticks which were fed on immunized
      rabbits. Polyclonal rabbit antibodies to tick saliva did not react with rHLS1,
      suggesting that native HLS1 was not secreted into the host during tick feeding.
      rHLS1 could be a potential candidate for a cocktail anti-tick vaccine.

PMID- 12798627
TI  - Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP70,
      HSP30 and SAG1 genes.
AB  - The vaccination with Toxoplasma gondii heat shock protein 70 (T.g.HSP70) gene (a
      virulent tachyzoite-specific) induced the most prominent reduction in T. gondii
      loads in various organs of B6 and BALB/c mice at the acute and chronic phases of
      toxoplasmosis compared with T.g.HSP30 (a bradyzoite-specific) and SAG1 (a
      tachyzoite-specific) genes. A single gene gun vaccination with 2 microg of
      T.g.HSP70 gene induced a significant reduction in the number of T. gondii
      organisms compared with 50 microg of T.g.HSP70 gene vaccination by intramuscular
      (i.m.) or intraperitoneal (i.p.) injection. The vaccine effects of T.g.HSP70 gene
      persisted for more than 3 months.

PMID- 12798628
TI  - Optimising vaccination strategies in equine influenza.
AB  - A stochastic model of equine influenza (EI) is constructed to assess the risk of
      an outbreak in a Thoroughbred population at a typical flat race training yard.
      The model is parameterised using data from equine challenge experiments conducted
      by the Animal Health Trust (relating to the latent and infectious period of
      animals) and also published data on previous epidemics (to estimate the
      transmission rate for equine influenza). Using 89 ponies, an empirical
      relationship between pre-challenge antibody and the probability of becoming
      infectious is established using logistic regression. Changes in antibody level
      over time are quantified using published and unpublished studies comprising 618
      ponies and horses. A plausible Thoroughbred population is examined over the
      course of a year and the model is used to assess the risk of an outbreak of EI in
      the yard under the current minimum vaccination policy in the UK. The model is
      adapted to consider an alternative vaccination programme where the frequency of
      vaccination in older horses (2-year-olds and upwards) is increased. Model results
      show that this practical alternative would offer a significant increase in
      protection. Spread of infection between yards is also considered to ascertain the
      risk of secondary outbreaks.

PMID- 12798629
TI  - Comparison of PorA VR types and porA promoter sequence from Neisseria
      meningitidis B isolated from non-immunised children and vaccine failures
      immunised with a serogroup B outer membrane protein vaccine.
AB  - PorA protein is an important component of group B meningococcal protein-based
      vaccines. The goals of this study were: (i) to classify the non-serosubtypable
      strains recovered from vaccine failures and controls by porA variable region (VR)
      type; (ii) to investigate if point mutations of VRs of the porA gene are present
      in P1.19,15 strains recovered from vaccine failures and controls; (iii) to
      investigate if nucleotide sequence variation in the promoter region of porA gene
      is related to low expression of PorA protein. VR type P1.19,15 predominated in
      younger vaccine failures (3-47 months) compared to older failures (48-83 months).
      No changes in VRs of porA were observed in 46 P1.19,15 strains studied. A
      promoter spacer of 16bp and 10 guanidine residues in the polymeric G tract was
      detected in five of six strains with weak PorA expression. Overall, this study
      indicated that lack of antibody response was probably the major cause of low
      vaccine efficacy in young children.

PMID- 12798630
TI  - Reflections on the meningococcal group C infection immunisation campaign: views
      from the sharp end.
AB  - In July 1999, the Department of Health launched a campaign to immunise all
      children aged from 0-17 years with a new vaccine giving protection against
      meningococcal group C infection. Following the campaign, a survey of Immunisation
      Co-ordinators in England was conducted to identify strengths and weaknesses of
      the campaign. This paper summarises the main findings.

PMID- 12798631
TI  - Enhancement of Sm-p80 (large subunit of calpain) induced protective immunity
      against Schistosoma mansoni through co-delivery of interleukin-2 and interleukin
      12 in a DNA vaccine formulation.
AB  - Schistosomiasis afflicts an estimated 200 million people in 76 countries and an
      additional 600 million people are at risk of acquiring this infection. Even
      though effective anthelmintic treatment and snail eradication control programs
      exist, the discovery of an effective vaccine still remains the most potentially
      powerful means of control for this disease. We have concentrated on a vaccine
      candidate (large subunit of calpain or Sm-p80) because of its potential in
      conferring protection against challenge infection and its pivotal role in surface
      membrane biogenesis of schistosomes. Since surface membrane renewal is a major
      phenomenon employed by hemohelminths to evade host immune system; an immune
      response directed against Sm-p80 should make the parasite prone to immune
      clearance from the host by both providing a well-targeted attack and by
      potentially inhibiting the surface membrane biogenesis process. In the present
      study, we have utilized DNA immunization protocols using Sm-p80 with plasmids
      encoding interleukin-2 (IL-2) and interleukin-12 (IL-12). Sm-p80 by itself
      provided a 39% protection (P</=0.0001) against challenge infection in C57BL/6
      mice. This protection was increased to 57% (P</=0.0001) when plasmid encoding IL
      2 was co-administered with Sm-p80 DNA. Co-injection of plasmid DNA encoding IL-12
      with Sm-p80 DNA yielded a protection level of 45% (P</=0.0001). Statistically,
      the protection conferred by including IL-2 and IL-12 was significantly greater
      than when only the Sm-p80 was used. Sm-p80 DNA by itself elicited strong
      responses that includes IgG(2A) and IgG(2B) antibody isotypes. The introduction
      of IL-2 DNA with Sm-p80 DNA led to an increase in total IgG and IgG(2A) and
      IgG(2B) titres. Whereas co-administration of IL-12 DNA with Sm-p80 DNA resulted
      in the augmentation of only total IgG and IgG(2A). This data reinforces the
      potential of Sm-p80 as an excellent candidate for a schistosomiasis vaccine.

PMID- 12798632
TI  - Optimization of epicutaneous immunization for the induction of CTL.
AB  - The immune system of the skin has recently been exploited for the development of
      non-invasive vaccine technologies. However, one of the limitations of current
      vaccine protocols is the inefficient priming of cytotoxic T lymphocytes (CTL). In
      this study, we report that the application of either an immunodominant class I
      MHC restricted ovalbumin peptide or whole ovalbumin protein, to tape-stripped
      skin together with the co-application of the bacterial enterotoxin cholera toxin
      (CT) induces antigen-specific CTL. Tape-stripping (TS) was found to enhance the
      magnitude of antibody responses to co-administered protein and to promote the
      generation of antigen-specific IgG(2a) responses. As well, both cholera toxin and
      tape-stripping enhanced epidermal dendritic cell (DC) immigration into draining
      lymph nodes. The adjuvant effect of co-administered cholera toxin and tape
      stripping in promoting CTL priming was not dependent on IL-12. Epicutaneous
      immunization has previously been shown to induce robust antibody responses to
      administered protein antigen. We now demonstrate the induction of robust and
      persistent CTL responses to epicutaneously administered protein antigen.
      Epicutaneous immunization is cheap, simple and effective. These findings suggest
      the potential use of the skin for the generation of protective immune responses
      to both viral and tumor challenge.

PMID- 12798633
TI  - Gene gun immunization in a preclinical model is enhanced by B7 targeting.
AB  - DNA vaccines have great potential but despite the promise shown in rodent models,
      responses in large animals, including humans, have been disappointing.
      Furthermore, gene gun delivery of DNA has been used to improve these responses.
      However, most cells that are transfected are not the professional antigen
      presenting cells (APC) which are critical for generating the primary immune
      response. Here, we show that in the large animal model of the pig, the
      combination of the use of gene gun delivery and a DNA vector that targets antigen
      presenting cells by expressing a CTLA4-ovalbumin (OVA) fusion antigen, leads to
      enhanced ovalbumin specific serum IgG, IgA, IgG1 and IgG2 immune responses.

PMID- 12798635
TI  - Porcine Ig isotypes: function and molecular characteristics.
AB  - In pigs, protection against the toxigenic extra-cellular bacterium Actinobacillus
      pleuropneumoniae was correlated with an increased IgG(1):IgG(2) ratio of
      haemolytic toxin-specific antibodies. In all species so far studied, IgG isotype
      expression is controlled by Type 1 (IFN-gamma, IL-12) and Type 2 (IL-4, IL-10)
      cytokines which dictate immune response polarization to cell-mediated (CMI) or
      antibody-mediated immunity (AMI), respectively. Thus, immunoglobulin (Ig)
      isotypes reflect Type 1 or Type 2 immune responses. Immunoglobulin isotype
      production by porcine B-cells cultured in the presence of recombinant porcine
      (rp) cytokines varies by individual, however pigs tend to generate a high
      IgG(1):IgG(2) ratio in response to rp IL-10 and the inverse in response to rp IFN
      gamma or rp IL-12. Differential Ig isotype production should favor an isotype
      with a functional advantage to control the inciting infection and disease.
      However, functions of porcine Ig isotypes have not been described. To compare
      function of porcine IgM, IgG(1) and IgG(2) of defined specificity for hen
      eggwhite lysozyme (HEWL), Ig isotypes were affinity purified from serum by HEWL
      specificity and by isotype-specific mouse monoclonal antibodies. Their ability to
      activate complement (C') and to opsonize was tested in vitro. Porcine IgG(2) had
      greater guinea pig C' activating ability than did IgG(1). Neither isotype
      opsonized HEWL-conjugated sheep erythrocytes in vitro. Amino acid sequence
      analysis of IgG isotypes revealed that all subclasses have putative C' binding
      sites but that IgG(2a), IgG(2b) and IgG(4) were more flexible in the middle hinge
      region than IgG(1) and IgG(3) and would likely activate C' more efficiently.
      Thus, porcine IgG isotypes associated with resistance and susceptibility to
      disease also differ in their actual and predicted biological functions.

PMID- 12798634
TI  - The immunogenicity of oral poliomyelitis vaccine in a primary vaccination series
      at 2, 4 and 6 months given concurrently with Hib, hepatitis B and diphtheria,
      tetanus and whole-cell pertussis vaccines administered as three separate
      injections or as a combination pentavalent vaccine.
AB  - The increasing number of infant immunisations has spurred development of novel
      combination vaccines. This investigation assesses the immunogenicity of oral
      poliomyelitis vaccine (OPV) under current and possible new conditions, to help
      ensure vaccination regimes continue to provide optimal protection against polio
      in the final stages of polio eradication. Neutralising antibody titres were
      measured in approximately 200 infants immunised with OPV at 2, 4 and 6 months in
      tandem with either a combined pentavalent liquid Haemophilus influenza B (Hib),
      hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine or three
      separate but concurrently administered licensed vaccines (diphtheria, tetanus and
      whole-cell pertussis (DTP), lyophilised Hib, and hepatitis B). Following three
      doses of OPV, at least 98% of infants demonstrated neutralising antibodies at 1:8
      to each poliovirus type under both vaccination regimes, and geometric mean titres
      (GMTs) well above the suggested protective titre were also observed for all
      poliovirus types. OPV appears to be effective not only in producing protective
      antibody titres in an extremely high proportion of infants when given in
      combination with currently licensed vaccines, but also when administered together
      with the combination pentavalent vaccine under study. This is encouraging for the
      continued role of OPV in infant immunisation.

PMID- 12798636
TI  - CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection
      in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal
      fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)) formulated
      in oil-based Montanides.
AB  - The 19kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface
      protein-1 (MSP1(19)), an analog of the leading falciparum malaria vaccine
      candidate, induces protective immunity to challenge infection when formulated
      with complete/incomplete Freund's adjuvant (CFA/IFA), an adjuvant unsuitable for
      use in humans. In this study, we investigate Montanide ISA51 and Montanide ISA720
      as well as CpG oligodeoxynucleotide (ODN) as adjuvants for induction of immunity
      to MSP1(19). Mice immunized with MSP1(19) adjuvanted with Montanide ISA51 were
      protected even though some mice experienced low-grade parasitemia before
      resolving the infection. Mice immunized with MSP1(19) adjuvanted with Montanide
      ISA720 showed delayed patent parasitemia with all mice ultimately succumbing to
      infection. Interestingly, when the synthetic CpG ODN 1826 was included in either
      Montanide formulation, mice were completely protected with no parasites detected
      in the blood. MSP1(19)-specific antibodies in MSP1(19)-immunized mice adjuvanted
      with Montanide ISA51 or Montanide ISA720 showed predominantly IgG1 antibody and
      low levels of IgG2a. CpG ODN 1826 significantly enhanced both IgG1 and IgG2a
      antibody responses in Montanide ISA51-adjuvanted mice but significantly enhanced
      only the IgG2a antibody response in Montanide ISA720-adjuvanted mice. To
      investigate the relative roles of antibody and CD4(+) T cells in protection,
      MSP1(19)-immunized mice adjuvanted with Montanide ISA720 and CpG ODN 1826 were
      depleted of CD4(+) T cells just prior to challenge. Results showed that three of
      nine immunized/T cell depleted mice died following infection. These results
      suggest that antibody and CD4(+) T cells are critical for protection following
      immunization with MSP1(19) adjuvanted with Montanide and CpG ODN and that the
      formulation of a human malaria vaccine candidate in Montanide ISA720 or ISA51
      together with human compatible CpG ODN would be useful for improving efficacy.

PMID- 12798638
TI  - Immunity against measles in populations of women and infants in Poland.
AB  - During the 1997-1998 measles epidemic in Poland a high attack rate occurred in
      infants up to 1 year of age (24.6/100,000 in comparison with 5.5/100,000 in total
      population). Routine vaccination against measles for infants aged 13-15 months
      was introduced in Poland in 1975, and a second dose added in 1991. The
      recommended age for measles vaccination was based on information gathered in
      years when most mothers had a natural measles. Nowadays, many mothers have
      received measles vaccine. Early loss of passively acquired measles antibody may
      occur in infants of women who received measles vaccine, because measles vaccine
      induces lower antibody titres than does natural infection. Therefore, measles
      specific antibody titres were determined among vaccinated and unvaccinated women
      as well as among infants, whose mothers were born after 1976 and likely were
      vaccinated (Group 1), and those, whose mothers were born before 1969 and likely
      have had a natural measles (Group 2). All women that were born in prevaccination
      era had significantly higher geometric mean titre (GMT) of measles antibody than
      those who were vaccinated (P<0.001). Also infants from Group 2 at every age had
      higher GMT of measles antibody than those of Group 1. The antibody decay was
      significantly faster among infants whose mothers acquired immunity by measles
      vaccination. Because nowadays the majority of women in childbearing age are
      vaccinated against measles, earlier vaccination in the infants should be
      considered.

PMID- 12798637
TI  - Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine
      evaluation group NIAID-sponsored Phase I and II clinical trials.
AB  - This report evaluates long-term safety data from 3189 human immunodeficiency
      virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51
      National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I
      and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit
      vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia
      vector recombinant envelope vaccines (7 studies), canarypox vector recombinant
      vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine
      (1 study). During the 12,340 person-years of follow-up, participants were
      monitored for adverse events including immune dysfunction/autoimmunity,
      anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence
      that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete
      Freund's caused serious toxicity, but otherwise no safety problems considered
      serious were identified for any of the vaccines and adjuvants studied. These data
      serve to solidify the growing safety base of current vaccine technologies
      utilized in candidate vaccines for HIV-1 infection.

PMID- 12798639
TI  - Frequent nasal administrations of recombinant cholera toxin B subunit (rCTB)
      containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum
      and mucosal immune responses in the presence of anti-rCTB antibodies.
AB  - Vaccination via a mucosal route is a very attractive means for immunization,
      because both local and systemic immune responses are inducible and vaccines can
      be administered easily and safely from infants to elderly persons. For developing
      widely applicable mucosal vaccines using recombinant cholera toxin B subunit
      (rCTB) as a safe adjuvant, we examined whether frequent nasal administrations of
      rCTB-containing same and different vaccines could induce antigen-specific immune
      responses without induction of systemic tolerance and suppression by pre-existing
      anti-rCTB immunity. Ten repetitive nasal administrations to mice of tetanus
      toxoid (TT) + rCTB or diphtheria toxoid (DT) + rCTB raised and maintained high
      levels of antigen- and rCTB-specific serum IgG including high levels of
      tetanus/diphtheria antitoxin titres and raised nasal, salivary, lung, vaginal and
      fecal secreted IgA, suggesting that the regimen did not induce systemic tolerance
      to TT/DT and rCTB. Mice successively received repetitive five doses of TT as the
      first antigen and subsequent five doses of DT as the second antigen, and vice
      versa, raised serum IgG to the second antigen at various levels including low but
      sufficient protective levels of antitoxin titres and induced mucosal IgA in the
      lungs, the vaginas and feces, but hardly in the nasal secretions and salivas.
      After an interval of 22 weeks between the dosage of the first and second
      antigens, mice induced serum IgG to the second antigen at high levels and mucosal
      IgA in all sites. In conclusion, anti-TT and -DT serum and mucosal antibody
      responses induced by repeated intranasal immunization using rCTB adjuvant lasted
      for a long period, and for improving the effectivity of vaccination, different
      rCTB-containing vaccines should be administered at appropriate intervals.

PMID- 12798640
TI  - CD40 ligand (CD154) improves the durability of respiratory syncytial virus DNA
      vaccination in BALB/c mice.
AB  - Respiratory syncytial virus (RSV) infection is the single most important cause of
      serious acute respiratory illness in children <1 year of age worldwide, and is
      associated with life-threatening pneumonia or bronchiolitis in the elderly.
      Current vaccine strategies include live, attenuated virus, subunit and DNA
      vaccines, however, none have been sufficiently safe, or shown to induce
      satisfactory long-term immunity, thus immune modulators are being considered to
      enhance the effectiveness of RSV vaccines. In this study, we examine CD40 ligand
      (CD40L) as an immune modulator to enhance the durability of DNA vaccines encoding
      RSV F and/or G glycoproteins in BALB/c mice. The addition of CD40L to DNA
      vaccines encoding the F glycoprotein enhanced virus clearance and some aspects of
      the immune response to RSV challenge, suggesting that CD40L may enhance the
      durability of RSV DNA vaccines.

PMID- 12798641
TI  - Response of calves persistently infected with noncytopathic bovine viral diarrhea
      virus (BVDV) subtype 1b after vaccination with heterologous BVDV strains in
      modified live virus vaccines and Mannheimia haemolytica bacterin-toxoid.
AB  - Seronegative persistently infected (PI) calves with bovine viral diarrhea virus
      (BVDV) subtype 1b were vaccinated with each of four modified live virus (MLV)
      BVDV vaccines and a Mannheimia haemolytica bacterin-toxoid. Nasal swabs and
      peripheral blood leukocytes (PBL) were collected for virus isolation and serums
      were collected after vaccination and tested for BVDV1a, BVDV1b, BVDV2, bovine
      herpesvirus-1 (BHV-1), bovine parainfluenza-3 virus (PI-3V), and bovine
      respiratory syncytial virus (BRSV) antibodies. M. haemolytica and Pasteurella
      multocida antibodies were detected using ELISA procedures. None of the PI calves
      developed mucosal disease (MD) after MLV vaccination. None of the BVDV PI calves
      seroconverted to BVDV1b after MLV vaccination. Calves receiving MLV vaccines
      seroconverted to the respective type/subtype in the vaccine. Calves receiving a
      MLV vaccine with noncytopathic (NCP) BVDV1 (subtype not designated) did not
      seroconvert to BVDV1a, BVDV1b, or BVDV2. The PI calves were positive for BVDV
      subtype 1b, in the PBL and nasal swabs throughout the study. Calves receiving
      each of three vaccines with known BVDV1a strains had BVDV1a positive samples
      after vaccination, in some but not all calves, up to Day 28. The PI BVDV1b calves
      did not respond with increased M. haemolytica antibodies after vaccination
      compared to BVDV negative calves receiving the same M. haemolytica vaccine.

PMID- 12798642
TI  - Standardisation and establishment of a rabies ELISA test in European laboratories
      for assessing the efficacy of oral fox vaccination campaigns.
AB  - A simple and rapid enzyme linked immunosorbent assay (ELISA) to detect rabies
      antibodies in field fox sera has been standardised and established in several
      European laboratories. The same panels of 100 coded sera were investigated by
      four laboratories using this ELISA assay and reference serum neutralisation
      techniques (fluorescent antibody virus neutralisation (FAVN) test and rapid
      fluorescent focus inhibition test (RFFIT)). This indirect ELISA technique is
      highly correlated with conventional seroneutralisation test on cell culture.
      Results obtained with this ELISA test provide an almost perfect agreement between
      laboratories while the agreement of FAVN test and RFFIT results is substantial
      and very satisfactory. In view of this study, this simple and rapid ELISA test is
      a suitable tool for evaluating the sero-conversion rate in fox populations
      following oral rabies vaccination campaigns in European countries.

PMID- 12798643
TI  - Pathogenicity and neurovirulence of a mutagen-attenuated Rift Valley fever
      vaccine in rhesus monkeys.
AB  - Rhesus macaques, intravenously inoculated with virulent Rift Valley fever virus,
      develop viremia and biochemical evidence of liver damage and serve as a model for
      human disease. Some of these monkeys suffer more serious disease with hemorrhagic
      phenomena and approximately 20% die with frank hemorrhage. Presently, the only
      Rift Valley fever vaccine approved for use in humans is a formalin-killed product
      that requires annual booster vaccinations. Efforts to produce an improved vaccine
      to replace the present vaccine have led to a mutagen-attenuated strain of Rift
      Valley fever virus that was found to be markedly attenuated for rhesus macaques
      and showed promise as a vaccine candidate for human use. Neurovirulence testing
      in rhesus monkeys showed that, while the vaccine was not completely innocuous,
      residual lesions were no more severe than the currently used 17D yellow fever
      vaccine.

PMID- 12798644
TI  - Construction and characterization of rhesus monkey rotavirus (MMU18006)- or
      bovine rotavirus (UK)-based serotype G5, G8, G9 or G10 single VP7 gene
      substitution reassortant candidate vaccines.
AB  - Group A rotaviruses are the single most important etiologic agents of severe
      diarrhea of infants and young children worldwide and have been estimated to be
      responsible for approximately 650,000-800,000 deaths annually in children <5-year
      old in the developing countries. Thus, the development of a safe and effective
      rotavirus vaccine has been a global public health goal. Epidemiologic
      surveillance of rotavirus VP7 (G) serotypes-genotypes conducted in various
      populations throughout the world has repeatedly shown that approximately 90% of
      the typeable rotavirus isolates belong to G1-G4. For these reasons, we have
      developed a rhesus rotavirus (RRV)-based or bovine rotavirus (UK)-based
      quadrivalent vaccine which is designed to provide antigenic coverage for G1-G4.
      More recently, G serotypes-genotypes other than G1-G4, including G5, G8-G10, have
      been detected in various parts of the world. Although the occurrence of such
      uncommon G types, except for G9, has been focal, still, in order to "be ready and
      prepared", we have constructed and characterized eight additional reassortant
      rotavirus vaccines, each of which bears a single human or bovine VP7 gene
      encoding G serotype 5, 8, 9 or 10 specificity and the remaining 10 genes of RRV
      strain MMU18006 or bovine rotavirus strain UK. These candidate vaccines could be
      evaluated singly in special populations or in combination with a RRV- or an UK
      based quadrivalent vaccine to broaden its G serotype specificity.

PMID- 12798645
TI  - Evaluation of the compatibility of a second generation recombinant anthrax
      vaccine with aluminum-containing adjuvants.
AB  - Recombinant protective antigen (rPA) is the active pharmaceutical ingredient in a
      second generation anthrax vaccine undergoing pre-clinical evaluation. This rPA
      vaccine differs from the currently licensed vaccine, anthrax vaccine adsorbed
      (AVA), in that the sole component is a recombinant form of protective antigen
      (PA). Unlike AVA the rPA vaccine contains no lethal factor (LF) or edema factor
      (EF), components of the two bipartite toxins, nor many other Bacillus anthracis
      related contaminating proteins that are present in AVA. The proposed clinical
      protocol involves adsorption of the rPA to an aluminum-based adjuvant. The
      adsorptive characteristics of rPA and two aluminum-containing adjuvants were
      examined in a physiological buffer with and without EDTA. Based on the pI of rPA
      (pI=5.6) and the zero charge point of aluminum hydroxide adjuvant (11.5) and
      aluminum phosphate adjuvant (4.5), it was predicted and demonstrated that rPA
      bound in a more efficient manner to aluminum hydroxide adjuvant than to aluminum
      phosphate adjuvant in the physiological buffer. Binding of the rPA to the
      aluminum hydroxide adjuvant was decreased by increasing amounts of phosphate in
      the buffer. The adsorptive capacity for rPA onto aluminum hydroxide adjuvant in
      the physiological buffer and in water were calculated to be 0.46 mg rPA/mg
      aluminum in DPBS and 0.73 mg rPA/mg aluminum in water. This study also
      demonstrated that upon desorption from the aluminum hydroxide adjuvant the rPA
      was physically intact and free of detectable aggregates. Further, the eluted
      material was biologically active in an in vitro cytotoxicity assay. Desorption
      was only possible after an overnight incubation of 2-8 degrees C and not after a
      room temperature incubation reflecting increased contact with the aluminum
      hydroxide adjuvant over time. These data suggest that the interaction between rPA
      and aluminum hydroxide adjuvant is predominantly electrostatic in character.

PMID- 12798646
TI  - Regional, but not systemic recruitment/expansion of dendritic cells by a pluronic
      formulated Flt3-ligand plasmid with vaccine adjuvant activity.
AB  - Regional recruitment of dendritic cells (DCs) by the local administration of
      granulocyte macrophage-colony stimulating factor (GM-CSF) or Flt3-ligand (Flt3L)
      has vaccine adjuvant activity. However, Flt3L, with its DC growth factor
      activity, has not been extensively studied as a vaccine adjuvant, particularly as
      a plasmid vector. We report that the intramuscular (IM) injection of a Flt3L
      plasmid (pNGVL-hFlex), when formulated in a pluronic carrier (SP1017, Supratek
      Pharma, Inc., Laval, Que., Canada), recruits DC to the injection site and
      regional lymph nodes (LNs) and augments immune responses to a p17 HIV plasmid
      vaccine to a greater extent than the injection of a naked DNA vaccine alone.
      Following IM administration of pNGVL-hFlex, Flt3L mRNA, Flt3L protein and
      infiltrating DC accumulate at the injection site. The number of DC in the
      draining LNs are also significantly increased with the greatest increase observed
      following injection of 2.5 microg of pNGVL-hFlex formulated in 0.01% SP1017. Flow
      cytometric studies demonstrate that the LN-infiltrating DC is mainly of the
      CD11c(+)CD11b(-) phenotype (IL-12 producing). Further, the co-injection of pNGVL3
      hFlex and p17 HIV plasmids, formulated in SP1017, significantly increases the
      immune responses to the plasmid vaccine (pVAX-gag). The co-injection of pVAX-gag
      and pNGVL3-hFlex, formulated in SP1017, significantly increase delayed-type
      hypersensitivity responses and the numbers of antigen (Ag)-specific interferon
      gamma secreting T cells in the spleen (Enzyme Linked Immune Spot (ELISpot)
      assay), compared to mice immunized with pVAX-gag formulated in SP1017 alone. We
      conclude that the IM injection of pNGVL-hFlex with SP1017 can increase the number
      of DC in draining LN and at the site of injection, thereby providing adjuvant
      activity for a plasmid vaccine resulting in a significantly increased, Ag
      specific T cell response.

PMID- 12798647
TI  - The protective efficacy of MSP4/5 against lethal Plasmodium chabaudi adami
      challenge is dependent on the type of DNA vaccine vector and vaccination
      protocol.
AB  - The enhancement of immunogenicity of malarial DNA vaccines is important if they
      are to have practical application in protecting against blood-stage malaria. Here
      we describe three different DNA vaccine vector types used in conjunction with the
      blood-stage merozoite surface protein 4/5 (MSP4/5), the murine homologue of
      Plasmodium falciparum MSP4 and MSP5, in an attempt to enhance survival against
      lethal Plasmodium chabaudi adami DS blood-stage challenge. MSP4/5 was inserted
      into VR1020 (secretory), monocyte-chemotactic protein-3 (MCP-3)
      (chemoattractant), and cytotoxic T-lymphocyte antigen 4 (CTLA4) (lymph node
      targeting) vectors. Mice were immunized intradermally via gene-gun, IM injection,
      or boosting with recombinant MSP4/5 protein. Antibody responses after boosting
      were predominantly of the IgG1 and IgE isotypes, with low avidity antibodies
      produced in DNA primed groups. Despite antibody responses comparable to
      recombinant protein immunization, boosting mice primed with antigens encoded by
      MCP-3 and CTLA4 vectors did not enhance survival compared to vector control
      groups. Gene-gun vaccination using VR1020/MSP4/5 followed by recombinant MSP4/5
      boosting, or gene-gun DNA vaccination alone using MCP-3/MSP4/5, resulted in
      enhanced survival compared to empty vector control mice. The results suggest that
      the enhancement of survival against lethal blood-stage malaria challenge after
      utilizing MSP4/5 DNA vaccination is therefore highly dependent on the route and
      type of vaccine vector employed.

PMID- 12798648
TI  - Protective efficacy of oral immunization with heat-killed Shigella flexneri 2a in
      animal model: study of cross protection, immune response and antigenic
      recognition.
AB  - Oral immunization of rabbits with four doses of 10(11) heat-killed Shigella
      flexneri 2a showed 100% protection against challenge with virulent S. flexneri
      2a. After orally immunizing Guinea pigs with four doses of heat-killed S.
      flexneri 2a 100% protection could be shown against ocular challenge with the same
      virulent S. flexneri 2a strain but this conferred no protection against challenge
      with Shigella dysenteriae type 1. In enzyme-linked immunosorbent assay (ELISA)
      and immunoblot experiments both whole cell lysate-envelope (WCL-E) fraction and
      outer membrane proteins (OMPs) were recognized by the antisera. Though protective
      mechanism in shigellosis is not established with certainty, outer membrane
      proteins (specially 38, 34, 23 and 20kDa proteins) may be the major antigens in
      the induction of protective immune responses as indicated by this observation.

PMID- 12798649
TI  - Oral immunisation with live aroA attenuated Salmonella enterica serovar
      Typhimurium expressing the Yersinia pestis V antigen protects mice against
      plague.
AB  - Bubonic and pneumonic plague are caused by the bacterium Yersinia pestis. The V
      antigen of Y. pestis is a protective antigen against plague. In this study, an
      aroA attenuated strain of Salmonella enterica serovar Typhimurium (SL3261) has
      been used to deliver the Y. pestis V antigen as a candidate oral plague vaccine.
      SL3261 was transformed with the expression plasmid pTrc-LcrV, containing the lcrV
      gene encoding V antigen. Immunoblot analysis showed V antigen expression in
      SL3261 in vitro and intragastric immunisation of mice with the recombinant
      Salmonella resulted in the induction of V antigen-specific serum antibody
      responses and afforded protection against Y. pestis challenge. However, the
      antibody responses induced by the recombinant Salmonella did not correlate with
      the protection afforded, indicating that immune responses other than antibody may
      play a role in the protection afforded against plague by this candidate vaccine.

PMID- 12798650
TI  - Immunization with recombinant paraflagellar rod protein induces protective
      immunity against Trypanosoma cruzi infection.
AB  - In the present study, we have produced recombinant paraflagellar rod proteins
      (PFR) and report their use for successful vaccination of mice against Trypanosoma
      cruzi. This protection is associated with a highly polarized type 1 cytokine
      production profile. Additionally, we have analyzed the gene sequence encoding PFR
      2 to determine the degree of conservation among seven highly diverse strains of
      T. cruzi, and found it to be highly conserved. The results presented here
      indicate that the PFR antigens are highly conserved, and immunization with rPFR
      1, PFR-2, or an equimolar mix of the PFR-1, -2, and -3 proteins provides
      protective immunity against Trypanosoma cruzi.

PMID- 12798651
TI  - Genetic immunization with LYT1 or a pool of trans-sialidase genes protects mice
      from lethal Trypanosoma cruzi infection.
AB  - Genetic immunization with a limited set of genes has been demonstrated to be an
      effective means of protecting mice from a normally lethal challenge of
      Trypanosoma cruzi. The goal of this study was to expand the diversity of genes
      assessed as genetic vaccine candidates. Screening a T. cruzi amastigote cDNA
      expression library with anti-amastigote monoclonal antibodies resulted in the
      identification of two genes, the previously identified flagellar Ca(2+) binding
      protein, FCaBP, and a novel homologue of the adaptin AP-3 complex beta3 subunit,
      Tcbeta3. A third gene, LYT1, recently identified as a secreted T. cruzi protein
      involved in cell lysis and infectivity, and was selected. Although peptides from
      all three genes were found to be targets of cytotoxic T cell responses in
      chronically infected mice, only immunization with LYT1 protected mice from a
      normally lethal challenge of T. cruzi. As an alternative to testing individual T.
      cruzi genes as vaccines, pools of genes from the trans-sialidase (TS) and mucin
      families were assessed in vaccination studies. Immunization with pools of TS but
      not mucin genes provided protection against a normally lethal challenge of T.
      cruzi. This study demonstrates that the ability of T. cruzi proteins to elicit
      immune responses in infected hosts does not necessarily associate with the
      ability to induce protection and that both the products of single genes and multi
      gene families may serve as effective vaccines.

PMID- 12798652
TI  - Mucosal co-administration of cholera toxin and influenza virus hemagglutinin-DNA
      in ponies generates a local IgA response.
AB  - We have previously demonstrated that equine influenza virus hemagglutinin (HA)
      DNA vaccination protects ponies from challenge infection, and induces protective
      IgGa and IgGb responses. However, this approach does not induce a nasal IgA
      response. The objective of this study was to examine the value of cholera toxin
      (CT) administration as an adjuvant for intranasal HA DNA vaccination, and to
      measure protection 3 months after DNA vaccination. After an immunogenic dose of
      CT was determined, ponies were immunized on two occasions by intranasal
      administration of HA DNA and cholera toxin, or HA DNA alone. Ponies in both
      groups received two additional HA DNA particle mediated vaccinations at skin and
      mucosal sites. Antibody responses, and protection from challenge infection 3
      months after the last vaccination were studied and compared to an influenza virus
      naive control group. Ponies in both vaccination groups produced virus-specific
      IgG antibodies in serum following vaccination and showed clinical protection from
      challenge infection 3 months after the last vaccination. Co-administration of CT
      plus HA DNA vaccination induced a nasal IgA response. In addition, analysis of
      antibody titers in nasal secretions indicated local production of nasal IgGb,
      which was amplified by CT administration.

PMID- 12798656
TI  - Protective role of n-3 lipids and soy protein in osteoporosis.
AB  - It is well established that bone loss due to estrogen deficiency after menopause
      is greater in women consuming higher quantities of animal protein than in women
      consuming vegetable protein, particularly soy protein. Besides the dietary
      protein source altering bone loss, it has also been postulated recently that the
      source of a higher n-6/n-3 ratio in dietary oils is implicated in causing
      osteoporosis. Both animal and human studies have indicated that an increased
      intake of n-6 fatty acids from vegetable oils elevates prostaglandin E(2) levels
      as well as pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha.
      Interestingly, it has been found that lack of estrogen also increases the
      production of these cytokines by immune cells and thereby activates osteoclasts
      during the peri-menopausal period. We speculated that the use of n-3 fatty acids
      and soy protein, which are known to act as anti-inflammatory and down regulate
      pro-inflammatory cytokines, may also protect against bone loss by decreasing
      osteoclast activation and bone resorption. Similar to the results of others, our
      ongoing studies indeed show that the bone loss in ovariectomized mice is
      significantly attenuated by feeding diets enriched with either fish oil or soy
      protein when compared to corn oil and casein-fed mice. One of the mechanisms
      appears to be decreasing the activation of receptor activator of NF-kappaB ligand
      (RANKL) on T cells, which has been found to increase osteoclast activation along
      with increasing pro-inflammatory cytokines in OVX mice. Since hormone replacement
      therapy has been found to cause adverse effects, further both animal and human
      studies are required with moderate soy protein and fish oil supplements in
      understanding the mechanisms involved in altering immune function and bone loss
      during menopause in women and aging in men.

PMID- 12798657
TI  - Possible role of oxidized lipids in osteoporosis: could hyperlipidemia be a risk
      factor?
AB  - Several years ago we hypothesized that products of lipid and lipoprotein
      oxidation may contribute to pathophysiology of osteoporosis (F. Parhami, Curr.
      Opin. Lipidol. 8 (1997) 312), and that their effects on artery wall and bone
      cells may explain the parallel development of osteoporosis and atherosclerosis in
      the same subjects (R. Boukhris, JAMA 219 (1972) 1307; M.A. Frye, Bone Miner. 19
      (1992) 185). Since then, new evidence has accumulated in support of this
      hypothesis and its possibility is being further tested by investigators in both
      vascular and bone fields (A.D. Watson, J. Biol. Chem. 272 (1997) 13597). This
      review will summarize the evidence to date that support the role of oxidized
      lipids in osteoporosis, and will address some of the issues that need further
      examination in order to establish whether hyperlipidemia and susceptibility to
      lipid oxidation may serve as risk factors for osteoporosis.

PMID- 12798658
TI  - Effects of dietary fats on bone health in advanced age.
AB  - Evidence is accumulating that dietary lipids play an important role in bone
      health. Most of the data supporting the effects of lipids on bones have been
      collected in young adult and/or developing animals. Based upon this work,
      mechanisms have been proposed to explain how lipids act to enhance or inhibit
      bone resorption and deposition. Little work, however, has been done in older
      models. Since osteoporosis primarily afflicts the elderly, such work is needed in
      order to determine if mechanisms relevant to the young differ in advanced age,
      and to develop effective interventions for this especially vulnerable segment of
      the population. This article reviews evidence that dietary lipids are important
      to bone health in older individuals, and describes possible mechanisms that may
      be of particular relevance to the elderly. Specifically, studies supporting the
      influence of dietary lipids on calcium excretion, growth hormone secretion, fatty
      acid metabolism, and osteoblast formation are reviewed.

PMID- 12798659
TI  - Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function
      and bone metabolism.
AB  - Recent investigations indicate that the type and amount of polyunsaturated fatty
      acids (PUFA) influence bone formation in animal models and osteoblastic cell
      functions in culture. In growing rats, supplementing the diet with omega-3 PUFA
      results in greater bone formation rates and moderates ex vivo prostaglandin E(2)
      production in bone organ cultures. A protective effect of omega-3 PUFA on
      minimizing bone mineral loss in ovariectomized rats has also been reported. The
      actions of omega-3 fatty acids on bone formation appear to be linked to altering
      osteoblast functions. Herein we describe experiments with MC3T3-E1 osteoblast
      like cells that support findings in vivo where omega-3 PUFA modulated COX-2
      protein expression, reduced prostaglandin E(2) production, and increased alkaline
      phosphatase activity. Other studies indicate that the dietary source of PUFA may
      affect protein expression of Cbfa1 and nodule formation in fetal rat calvarial
      cells.

PMID- 12798660
TI  - Dietary n-3 fats as adjunctive therapy in a prototypic inflammatory disease:
      issues and obstacles for use in rheumatoid arthritis.
AB  - Eicosanoids derived from the n-6 fatty acid, arachidonic acid, and the cytokines
      interleukin-1beta and tumour necrosis factor-alpha are involved in the signs and
      symptoms of inflammatory joint disease, as well as the cartilage degradation seen
      in established rheumatoid arthritis (RA). Then n-3 fatty acids in fish and fish
      oil can inhibit production of both eicosanoid and cytokine inflammatory mediators
      and therefore, have the potential to modify RA pathology. Epidemiological studies
      suggest that fish intake may be preventive for RA and double-blind placebo
      controlled studies demonstrate that dietary fish oil can alleviate the signs and
      symptoms of RA. The implementation of these findings will require among other
      things, a range of n-3 fat enriched foods, as well as physician awareness of the
      possibilities for dietary n-3 fat increases to be used as adjunctive therapy in
      RA.

PMID- 12798661
TI  - Dietary arachidonic acid suppresses bone turnover in contrast to low dosage
      exogenous prostaglandin E(2) that elevates bone formation in the piglet.
AB  - This study was designed to compare the effects of dietary arachidonic acid (AA)
      versus prostaglandin E(2) (PGE(2)) on bone cell metabolism and bone mass. Twenty
      eight piglets from 7 litters were randomized to 1 of 4 treatments for 15 days:
      fatty acid supplemented formula (FA: 0.8% of total fatty acids as AA and 0.1% of
      total fatty acids as DHA)+PGE(2) injections (0.1mg/kg/day), FA+saline injections,
      standard formula (STD: n-6:n-3 of 8:1) + PGE(2) injections or STD+saline
      injections. PGE(2) resulted in elevated osteoblast activity as indicated by
      plasma osteocalcin and also reduced urinary calcium excretion. Dietary FA
      resulted in reduced bone resorption as indicated by urinary N-telopeptide and
      reduced bone PGE(2). Both PGE(2) and FA treatments independently lead to elevated
      femur mineral content, but the combined treatment caused a reduction. Thus the
      mechanisms by which PGE(2) and FA lead to enhanced bone mass are distinct.

PMID- 12798662
TI  - Biomechanical bone strength and bone mass in young male and female rats fed a
      fish oil diet.
AB  - The study objective was to determine if male and female rats fed a diet rich in
      fish oil had femurs and vertebrae that were stronger and more resistant to
      fracture than rats not fed omega-3 long chain polyunsaturated fatty acids.
      Weanling rats were randomized to a control or a fish oil diet for 5 weeks.
      Feeding fish oil to males had no effect on biomechanical strength properties of
      femurs and vertebrae as measured by three point bending and compression,
      respectively. In contrast, females fed fish oil had reduced length growth and a
      lower vertebral peak load. These effects may have been partly mediated by a lower
      food intake but were not associated with differences in serum IGF-I, estradiol or
      urinary calcium. The effect of consuming a fish oil diet into later adulthood
      should be investigated to determine if femur strength is also affected among
      females.

PMID- 12798663
TI  - Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption.
AB  - Dietary supplementation with fish oil that contains omega-3 polyunsaturated fatty
      acids has been shown to enhance bone density as well as duodenal calcium uptake
      in rats. The latter process is supported by membrane ATPases. The present in
      vitro study was undertaken to test the effect of omega-3 fatty acids on ATPase
      activity in isolated basolateral membranes from rat duodenal enterocytes. Ca
      ATPase in calmodulin-stripped membranes was activated in a biphasic manner by
      docosahexanoic acid (DHA) (10-30 microg/ml) but not by eicosapentanoic acid
      (EPA). This effect was blocked partially by 0.5 microM calphostin (a protein
      kinase C blocker). DHA inhibited Na,K-ATPase (-49% of basal activity, [DHA]=30
      microg/ml, P <0.01). This effect could be reversed partially by 50 microM
      genistein, a tyrosine kinase blocker. EPA also inhibited Na,K-ATPase: (-47% of
      basal activity, [EPA]=30 microg/ml, P <0.01), this effect was partially reversed
      by 100 microM indomethacin, a cyclo-oxygenase blocker. Omega-3 fatty acids are
      thus involved in multiple signalling effects that effect ATPases in BLM.

PMID- 12798664
TI  - Benefit and risk of exercise on myocardial function in diabetes.
AB  - Regular physical activity promotes cardiorespiratory fitness and has been
      considered a cornerstone for non-pharmacological treatment of more than 17
      million Americans with diabetes mellitus. Physical exercise has been shown to
      positively affect certain cardiovascular risk factors such as insulin resistance,
      glucose metabolism, blood pressure and body fat composition, which are closely
      associated with diabetes and heart disease. With the increasingly sedentary life
      style in our society, routine daily exercise of moderate intensity is highly
      recommended to reduce cardiovascular risk, the leading cause of death in diabetic
      patients. Exercise produces many beneficial effects to the heart function such as
      reduced incidence of coronary heart disease, attenuated severity of diabetic
      cardiomyopathy, improved cardiac performance, cardiac reserve and autonomic
      regulation. Nevertheless, many diabetic patients do not appear to gain much
      benefit from exercise or may even be at risk of performing physical exercise.
      This review summarizes the benefit and risk of exercise on diabetic heart
      function, with a special emphasis on myocardial and autonomic function.

PMID- 12798665
TI  - The effect of agmatine on the vascular reactivity in streptozotocin-diabetic
      rats.
AB  - AIM: We investigated the vascular effects of agmatine (decarboxylated
      arginine=AGM), an endogenous ligand for alpha(2)-adrenoceptors and imidazoline
      receptors, present in endothelium and smooth muscle, using the diabetic rat
      aortae. MATERIALS AND METHODS: Studies were performed in control group (0.2 ml
      i.p. saline, n=10), streptozotocin (STZ)-diabetic control group (60 mg kg(-1) STZ
      i.p., n=10), agmatine (AGM)-control group (5 mg kg(-1)day(-1) i.p. AGM for 1
      month, n=10), citrate-control group (0.2 ml 0.01 M, n=10), insulin-treated
      diabetic group ((3 U kg(-1) NPH+1 U kg(-1) regular insulin) twice per day, for 1
      month, n=10) and AGM-treated diabetic group (5 mg kg(-1)day(-1) i.p. for 1 month,
      n=10). All values are expressed as means+/-S.E.M. Statistical analysis of the
      data was performed using ANOVA followed by Tukey multiple comparisons test.
      RESULTS: One-month AGM-treatment significantly decreased the blood glucose levels
      of diabetic rats (502+/-44 mg dl(-1) to 343+/-31 mg dl(-1), P<0.001). Fast, slow
      and total components of responses to noradrenaline in all the experimental groups
      were not significantly affected by AGM-treatment. AGM reversed the decreased
      responses of acetylcholine (pD(2) and Inh.%, P<0.001 and P<0.05) in diabetic rats
      although it did not affect the responses of sodium nitroprusside in all groups.
      The contraction values of KCl in all groups were not affected by AGM-treatment.
      CONCLUSION: AGM-treatment could improve the increased blood glucose level,
      reverse the endothelial dysfunction and normalize the endothelium-dependent
      relaxation responses in STZ-diabetic rats.

PMID- 12798666
TI  - The effect of PARS inhibition on ileal histopathology, apoptosis and lipid
      peroxidation in LPS-induced obstructive jaundice.
AB  - In our experimental study, we investigated the protective effect of 3
      aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the
      ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced
      inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into
      five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4:
      OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In
      Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and
      then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was
      administrated intraperitoneally at the fifth day and repeated daily for 3 days
      and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group
      5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h
      10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3
      days. At the eighth day, rats were sacrificed. Blood samples were taken for
      detection of serum MDA levels. Ileum samples were taken after relaparotomy for
      histopathological examination to evaluate the endotoxin-related intestinal injury
      and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities.
      There was marked destruction of villous and crypt epithelial cells and extensive
      apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the
      scores of intestinal mucosal damage and apoptotic cells were reduced
      significantly (P<0.05). On the other hand, the scores of intestinal mucosal
      damage and apoptotic cells were not improved in Group 5. After the administration
      of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased
      as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal
      damage and apoptotic loss of intestinal epithelial cells significantly if it was
      administrated before LPS. However, 3-AB failed to prevent the mucosal damage and
      apoptotic loss of intestinal epithelial cells significantly if there was
      established endotoxemia in OJ.

PMID- 12798667
TI  - In vivo antioxidant activity of polysaccharide fraction from Porphyra haitanesis
      (Rhodephyta) in aging mice.
AB  - Sulfated polysaccharide fraction F2 from Porphyra haitanesis (Rhodephyta) showed
      inhibitory effect on the in vitro lipid peroxidation. In the present study, the
      age-related changes in the antioxidant enzyme activity, lipid peroxidation, and
      total antioxidant capacity (TAOC) in different organs in mice were investigated
      and the in vivo antioxidant effect of F2 in aging mice was checked. Increased
      endogenous lipid peroxidation and decreased TAOC were observed in aging mice.
      Intraperitoneal administration of F2 significantly decreased the lipid
      peroxidation in a dose-dependent manner. F2 treatment increased TAOC and the
      activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in all
      the organs tested in aging mice. It is concluded that the sulfated polysaccharide
      fraction F2 can be used in compensating the decline in TAOC and the activities of
      antioxidant enzymes and thereby reduces the risks of lipid peroxidation.

PMID- 12798668
TI  - Evaluation of the anti-inflammatory and anti-nociceptive effects of different
      antidepressants in the rat.
AB  - The present study was designed to compare the anti-inflammatory and anti
      nociceptive effects of different classes of antidepressant drugs on the
      carrageenan paw oedema and tail-electric stimulation assays in the rat. Drugs
      were intraperitoneally administered 30 min prior to carrageenan or nociceptive
      testing. The non-selective noradrenaline (NA) and serotonin (5-HT) reuptake
      inhibitors imipramine, amitriptyline and clomipramine displayed anti-inflammatory
      activity in the carrageenan model of paw inflammation. The maximal degree of
      oedema inhibitions seen with these agents were 28.8, 41.5 and 46.8% for 5, 10 and
      20 mg kg(-1) amitriptyline, 26.2, 38.2 and 51.4% for 3.75, 7.5 and 15 mg kg(-1)
      imipramine and 51.2 and 54.1% for 16 and 32 mg kg(-1) clomipramine, respectively.
      The heterocyclic agent trazodone significantly inhibited paw oedema by 46 and 41%
      at 1 and 2h after dosing at the highest dose (40 mg kg(-1)) examined. Fluoxetine,
      a selective 5-HT reuptake inhibitor (SSRI) caused dose-related reduction of paw
      oedema, with 20.7% inhibition at the dose of 10 mg kg(-1). In contrast,
      sertraline, another SSRI caused dose-dependent enhancement of paw oedema. All
      antidepressant drugs in the study showed anti-nociceptive properties in the tail
      electric stimulation assay with amitriptyline and trazodone being the most
      effective in this respect. Taken together, data in the present study confirm anti
      inflammatory and anti-nociceptive effect for some antidepressant drugs and
      indicate that SSRIs differently affects inflammation.

PMID- 12798669
TI  - Influence of sodium selenite on glycoprotein contents in normal and N
      nitrosodiethylamine initiated and phenobarbital promoted rat liver tumors.
AB  - Selenium in the form of sodium selenite is an essential micronutrient, that acts
      as an antioxidant/anticancer agent by its numerous macromolecules associated with
      them. This study emphasizes further evidence on its role as anticancer agent in
      experimental rats with N-nitrosodiethylamine (DEN) initiated (200 mg kg(-1) body
      weight) and phenobarbital (PB) promoted hepatoma. Serum, whole liver tissue
      (control animals, n=6), hepatoma and surrounding liver tissue samples from DEN
      treated rats and rats supplemented with selenite (n=6) were collected. Total
      protein, albumin, globulin and albumin/globulin ratio were investigated. Hexose,
      hexosamine and sialic acid were also quantified. Animals treated with DEN
      resulted in significantly decreased levels of total protein, albumin and
      albumin/globulin ratio; on the other hand, globulin content was increased
      significantly when compared to control rats. We have also observed significant
      increased levels of hexose, hexosamine and sialic acid in serum, whole liver
      tissue (control), hepatoma and surrounding liver tissue of control and
      experimental animals. Supplementation of selenite (4 ppm) either before
      initiation, during initiation and/or during promotion stages alters the above
      biochemical changes significantly. Thus, supplementations of selenite in cancer
      bearing animals reduce the adverse changes that occur during cancer condition.
      However, the chemopreventive/chemotherapeutic effect of selenite is more
      pronounced when it was supplemented before and/or during initiation of cancer
      when compared to promotion stage. Our results emphasize the role of sodium
      selenite in cancer and strongly indicate its role as an essential micronutrient
      in cancer chemoprevention and therapy.

PMID- 12798670
TI  - Physicochemical considerations in the iontophoretic delivery of a small peptide:
      in vitro studies using arginine vasopressin as a model peptide.
AB  - Transdermal iontophoresis (TI) is a physical enhancement technique to facilitate
      the delivery of primarily charged molecules across the skin. TI of peptides is
      influenced by a complex interplay of several factors and one of the main issues
      in optimizing iontophoretic delivery of peptides is to improve the transport
      efficiency. From this perspective, this study investigates the effect of the
      physicochemical parameters on the TI of a peptide arginine vasopressin (AVP). The
      permeation of AVP showed a linear dependence on the concentration of drug in the
      donor medium. The iontophoretic flux of AVP was strongly influenced by the pH of
      the donor solution. Increasing the pH from 5.16 to 7.4 resulted in a decrease in
      the enhancement ratio by 4.5 times. When the ionic strength was increased by
      varying the amount of NaCl from 0.05 to 0.25 M the flux was found to decrease by
      3.2 times. Replacing normal saline in the receptor compartment by HEPES buffer
      showed a resultant four times increase in drug permeation. The physiochemical
      parameters of the donor medium play a significant role in the efficiency of drug
      delivery by iontophoresis for a small peptide like AVP. Though electrorepulsion
      would be expected to be the main mechanism involved in the movement of charged
      molecules across the skin by iontophoresis, for peptides in the molecular weight
      range of AVP, other associated secondary effects like osmosis, electroosmosis and
      counter ion flow may also play a significant role in transport across the skin.

PMID- 12798671
TI  - Is the interaction between felbamate and valproate against seizures induced by 4
      aminopyridine and pentylenetetrazole in mice beneficial?
AB  - We compared the effects of adding a non-protective dose of valproate (VPA) to
      increasing single doses of felbamate (FBM) with those of monotherapy and vice
      versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced
      by 14 mg kg(-1) of 4-aminopyridine (4-AP) and by 110 mg kg(-1) of
      pentylenetetrazole (PTZ), and neurotoxicity by the rotarod test. The study also
      assessed changes in concentrations of anticonvulsants, gamma-aminobutyric acid
      (GABA) and glutamate in the whole brain. VPA increased the potency ratio of FBM
      against 4-AP (1.94, P<0.05) but not against PTZ. VPA increased the neurotoxicity
      of FBM (3.30, P<0.05) and the protective index of FBM was, therefore, reduced
      from 12.0 to 7.0 for the 4-AP model and from 11.8 to 5.2 for the PTZ model; VPA
      reduced brain FBM, and increased brain GABA in relation to FBM monotherapy. On
      the other hand, FBM increased the potency ratio of VPA against 4-AP (1.60,
      P<0.05) but not against the PTZ, and had no effect on the rotarod model.
      Therefore, the protective index increased from 1.1 to 1.6 for the 4-AP model and
      decreased from 1.9 to 1.7 for the PTZ model. FBM did not change brain VPA, and
      changes in brain GABA and glutamate were not clearly related to anticonvulsant
      effects. In conclusion, although the addition of a low dose of FBM to VPA was
      beneficial in the 4-AP model, the addition of a low dose of VPA to FBM was not;
      both combinations were disadvantageous in the PTZ model. This interaction appears
      to be pharmacodynamic because a pharmacokinetic mechanism was discarded.

PMID- 12798672
TI  - H3 agonist immepip markedly reduces cortical histamine release, but only weakly
      promotes sleep in the rat.
AB  - Presynaptic H3 receptors exert negative control on brain histamine synthesis and
      release and may thereby play a key role in the control of the sleep/wake cycle.
      This suggests that pharmacological stimulation by H3 receptor agonists may
      potentially decrease wakefulness and induce sleep. This study reports the effect
      of a potent and selective H3 agonist, immepip, on EEG assessed sleep/wake phases
      in Sprague-Dawley rats at doses that significantly modulate brain histamine
      release. Immepip injected intraperitoneally (i.p.) at 5 or 10 mg kg(-1) induced a
      sustained decrease in cortical histamine efflux as measured by in vivo
      microdialysis. In a separate experiment, rats were prepared for EEG/EMG recording
      and evaluated during the dark phase of their light/dark cycle. The results showed
      that the same i.p. doses of 5 and 10 mg kg(-1) of immepip was devoid of any
      significant impact on the sleep/wake phases (active awake, drowsiness and slow
      wave sleep), except for a slight, albeit significant, decrease in sleep onset
      latency. These results reveal that a marked H3 receptor agonist-mediated
      reduction in cortical histamine release is not corroborated by a significant
      sleep promoting effect and therefore question the hypnotic potential of H3
      agonists.

PMID- 12798673
TI  - Effects of Hypericum perforatum and paroxetine on rat performance in the elevated
      T-maze.
AB  - Hypericum perforatum extract exhibits an antidepressant effect and since several
      antidepressant drugs are also effective on generalised anxiety disorder (GAD) and
      panic disorders (PD), H. perforatum may possess some anxiolytic/antipanic effect.
      Thus, the aim of the present study was to evaluate the putative
      antipanic/anxiolytic effect of standardised H. perforatum extract (LI 160) on
      rats tested in the elevated T-maze, an animal model of innate (panic) and learned
      (generalised) anxiety, at doses that exhibit antidepressant-like activity. H.
      perforatum (150, 300 and 500 mg/kg, administered orally 24, 18 and 1h before the
      test) decreased the immobility time in the forced swim test. Rats were treated
      orally with H. perforatum (150 or 300 mg/kg) or paroxetine (5mg/kg) 24, 18, and
      1h before being tested in the elevated T-maze (subacute treatment). Immediately
      after this test, the animals were submitted to the open field to evaluate
      locomotor activity. Paroxetine was used as a positive control, since it was
      clinically effective in GAD and PD. Other groups of animals were submitted to the
      same drug treatment for 7 days (subchronic treatment). Paroxetine (5mg/kg)
      impaired inhibitory avoidance after subacute treatment, while subchronic
      administration increased one-way escape latency. Subacute treatment with H.
      perforatum (300 mg/kg) exerts a partial anxiolytic-like effect in the inhibitory
      avoidance task. Repeated administration of H. perforatum (300 mg/kg) induced an
      anxiolytic effect (decreased inhibitory avoidance) and an antipanic effect
      (increased one-way escape). No effect on locomotor activity was found with any
      treatment. Thus, the results suggest that H. perforatum extract could exert an
      anxiolytic and antipanic effect.

PMID- 12798674
TI  - Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced
      cerebral injury.
AB  - The present study is designed to investigate the effect of dietary flavanoid
      rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced
      cerebral injury. Global cerebral ischaemia was induced by occluding right and
      left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral
      infarct size was estimated using triphenyltetrazolium chloride staining. Elevated
      plus maze was employed to estimate short-term memory. Degree of motor
      incoordination was evaluated using inclined beam-walking test and lateral push
      test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was
      employed as an index of oxidative stress. Global cerebral ischaemia followed by
      reperfusion produced a significant impairment in short-term memory and motor
      coordination and produced a notable increase in mitochondrial TBARS.
      Administration of rutin and garlic oil before global cerebral ischaemia markedly
      reduced cerebral infarct size and attenuated impairment in short-term memory and
      motor coordination. Administration of sodium selenite either before or after
      global cerebral ischaemia markedly reduced cerebral infarct size and attenuated
      impairment in short-term memory and motor coordination. The protective effect of
      rutin, sodium selenite and garlic oil was accompanied by a marked decrease in
      mitochondrial TBARS. On the basis of these results, it may be suggested that
      rutin and garlic oil administrated before cerebral ischaemia may scavenge
      reactive oxygen species and consequently attenuate global cerebral ischaemia and
      reperfusion-induced cerebral injury. Sodium selenite administrated before and
      after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

PMID- 12798675
TI  - Determination of paroxetine in geriatric depression by high-performance liquid
      chromatography.
AB  - An HPLC method was developed for the determination of paroxetine in depressed
      geriatric patients. This method includes only one-step extraction of paroxetine
      from 1 ml of plasma with hexane:isoamyl alcohol (99:1, v/v). Separation was
      obtained using an RP select B column (250 mm x 4 mm, 5 microm) under isocratic
      conditions with UV detection (lambda=205 nm). The mobile phase was 0.05 mol/l
      sodium phosphate buffer, pH 5.0, and acetonitrile (50:50, v/v). The intra- and
      inter-assay accuracy and precision, determined as relative error and relative
      standard deviation, respectively, were less than 10%. The lower limit of
      quantification, with relative error and relative standard deviation of less than
      10%, was 5 ng/ml. Linearity was assessed in the 5-1250 ng/ml range and recovery
      was 80%. Neither endogenous compounds nor other drugs were found to interfere.
      The assay showed high specificity, even when patients were found to be on
      multiple medications. In conclusion, the present method, when compared to others
      reported in the literature, has advantages such as simplicity, selectivity and
      sensitivity as a routine procedure and can be applied to the therapeutic
      monitoring of depressed geriatric patients.

PMID- 12798676
TI  - Human polynucleotide phosphorylase, hPNPase, is localized in mitochondria.
AB  - The human gene encoding a polynucleotide phosphorylase (hPNPase) has been
      recently identified as strongly up-regulated in two processes leading to
      irreversible arrest of cell division: progeroid senescence and terminal
      differentiation. Here, we demonstrate that the hPNPase is localized in
      mitochondria. Our finding suggests the involvement of mitochondrial RNA
      metabolism in cellular senescence.

PMID- 12798677
TI  - Periodic epi-organization of the yeast genome revealed by the distribution of
      promoter sites.
AB  - The organization of transcription within the eukaryotic nucleus may be expected
      to both depend on and determine the structure of the chromosomes. This study
      shows that, in yeast, genes that are controlled by the same sequence-specific
      transcription factor tend to be regularly spaced along the chromosome arms; a
      similar period characterizes the spacing of origins of replication, although
      periodicity is less pronounced. The same period is found for most transcription
      factors within a chromosome arm. However, different periods are observed for
      different chromosome arms, making it unlikely that periodicity is caused by
      dedicated scaffolding proteins. Such regularities are consistent with a genome
      wide loop model of chromosomes, in which coregulated genes tend to dynamically
      colocalize in 3D. This colocalization may also involve co-regulated genes
      belonging to different chromosomes, as suggested by partial conservation of the
      respective positioning of different transcription factors around the loops. Thus,
      binding at genuine regulatory sites on DNA would be optimized by locally
      increasing the concentration of multimeric transcription factors. In this model,
      self-organization of transcriptional initiation plays a major role in the
      functional nuclear architecture.

PMID- 12798679
TI  - Mapping of functional domains in F plasmid partition proteins reveals a bipartite
      SopB-recognition domain in SopA.
AB  - Active partition of the F plasmid to dividing daughter cells is assured by
      interactions between proteins SopA and SopB, and a centromere, sopC. A close
      homologue of the sop operon is present in the linear prophage N15 and, together
      with sopC-like sequences, it ensures stability of this replicon. We have
      exploited this sequence similarity to construct hybrid sop operons with the aim
      of locating specific interaction determinants within the SopA and SopB proteins
      that are needed for partition function and for autoregulation of sopAB
      expression. Centromere binding was found to be specified entirely by a central 25
      residue region of SopB strongly predicted to form a helix-turn-helix structure.
      SopB protein also carries a species-specific SopA-interaction determinant within
      its N-terminal 45 amino acids, and, as shown by Escherichia coli two-hybrid
      analysis, a dimerization domain within its C-terminal 75 (F) or 97 (N15)
      residues. Promoter-operator binding specificity was located within an N-terminal
      66 residue region of SopA, which is predicted to contain a helix-turn-helix
      motif. Two other regions of SopA protein, one next to the ATPase Walker A-box,
      the other C-terminal, specify interaction with SopB. Yeast two-hybrid analysis
      indicated that these regions contact SopB directly. Evidence for the involvement
      of the SopA N terminus in autoinhibition of SopA function was obtained, revealing
      a possible new aspect of the role of SopB in SopA activation.

PMID- 12798678
TI  - Mg2+-induced variations in the conformation and dynamics of HIV-1 TAR RNA probed
      using NMR residual dipolar couplings.
AB  - The effects of divalent Mg(2+) on the conformation and dynamics of the stem-loop
      transactivation response element (TAR) RNA from HIV-1 have been characterized
      using NMR residual dipolar couplings (RDCs). Order matrix analysis of one bond
      13C-1H RDCs measured in TAR at [Mg(2+)]:[TAR] stoichiometric ratios of
      approximately 3:1 (TAR(3.0Mg)) and approximately 4.5:1 (TAR(4.5Mg)) revealed that
      Mg(2+) reduces the average inter-helical angle from 47(+/-5) degrees in TAR(free)
      to 5(+/-7) degrees in TAR(4.5Mg). In contrast to the TAR(free) state, the
      generalized degree of order for the two stems in TAR(4.5Mg) is found to be
      identical within experimental uncertainty, indicating that binding of Mg(2+)
      leads to an arrest of inter-helical motions in TAR(free). Results demonstrate
      that RDC-NMR methodology can provide new insight into the effects of Mg(2+) on
      both the conformation and dynamics of RNA.

PMID- 12798680
TI  - Cryo-negative staining reveals conformational flexibility within yeast RNA
      polymerase I.
AB  - The structure of the yeast DNA-dependent RNA polymerase I (RNA Pol I), prepared
      by cryo-negative staining, was studied by electron microscopy. A structural model
      of the enzyme at a resolution of 1.8 nm was determined from the analysis of
      isolated molecules and showed an excellent fit with the atomic structure of the
      RNA Pol II Delta4/7. The high signal-to-noise ratio (SNR) of the stained
      molecular images revealed a conformational flexibility within the image data set
      that could be recovered in three-dimensions after implementation of a novel
      strategy to sort the "open" and "closed" conformations in our heterogeneous data
      set. This conformational change mapped in the "wall/flap" domain of the second
      largest subunit (beta-like) and allows a better accessibility of the DNA-binding
      groove. This displacement of the wall/flap domain could play an important role in
      the transition between initiation and elongation state of the enzyme. Moreover, a
      protrusion was apparent in the cryo-negatively stained model, which was absent in
      the atomic structure and was not detected in previous 3D models of RNA Pol I.
      This structure could, however, be detected in unstained views of the enzyme
      obtained from frozen hydrated 2D crystals, indicating that this novel feature is
      not induced by the staining process. Unexpectedly, negatively charged molybdenum
      compounds were found to accumulate within the DNA-binding groove, which is best
      explained by the highly positive electrostatic potential of this region of the
      molecule, thus, suggesting that the stain distribution reflects the overall
      surface charge of the molecule.

PMID- 12798681
TI  - Crystal structure of the 2'-5' RNA ligase from Thermus thermophilus HB8.
AB  - The 2'-5' RNA ligase family members are bacterial and archaeal RNA ligases that
      ligate 5' and 3' half-tRNA molecules with 2',3'-cyclic phosphate and 5'-hydroxyl
      termini, respectively, to the product containing the 2'-5' phosphodiester
      linkage. Here, the crystal structure of the 2'-5' RNA ligase protein from an
      extreme thermophile, Thermus thermophilus HB8, was solved at 2.5A resolution. The
      structure of the 2'-5' RNA ligase superimposes well on that of the Arabidopsis
      thaliana cyclic phosphodiesterase (CPDase), which hydrolyzes ADP-ribose 1",2"
      cyclic phosphate (a product of the tRNA splicing reaction) to the monoester ADP
      ribose 1"-phosphate. Although the sequence identity between the two proteins is
      remarkably low (9.3%), the 2'-5' RNA ligase and CPDase structures have two
      HX(T/S)X motifs in their corresponding positions. The HX(T/S)X motifs play
      important roles in the CPDase activity, and are conserved in both the CPDases and
      2'-5' RNA ligases. Therefore, the catalytic mechanism of the 2'-5' RNA ligase may
      be similar to that of the CPDase. On the other hand, the electrostatic potential
      of the cavity of the 2'-5' RNA ligase is positive, but that of the CPDase is
      negative. Furthermore, in the CPDase, two loops with low B-factors cover the
      cavity. In contrast, in the 2'-5' RNA ligase, the corresponding loops form an
      open conformation and are flexible. These characteristics may be due to the
      differences in the substrates, tRNA and ADP-ribose 1",2"-cyclic phosphate.

PMID- 12798682
TI  - PspGI, a type II restriction endonuclease from the extreme thermophile Pyrococcus
      sp.: structural and functional studies to investigate an evolutionary
      relationship with several mesophilic restriction enzymes.
AB  - We present here the first detailed biochemical analysis of an archaeal
      restriction enzyme. PspGI shows sequence similarity to SsoII, EcoRII, NgoMIV and
      Cfr10I, which recognize related DNA sequences. We demonstrate here that PspGI,
      like SsoII and unlike EcoRII or NgoMIV and Cfr10I, interacts with and cleaves DNA
      as a homodimer and is not stimulated by simultaneous binding to two recognition
      sites. PspGI and SsoII differ in their basic biochemical properties, viz.
      stability against chemical denaturation and proteolytic digestion, DNA binding
      and the pH, MgCl(2) and salt-dependence of their DNA cleavage activity. In
      contrast, the results of mutational analyses and cross-link experiments show that
      PspGI and SsoII have a very similar DNA binding site and catalytic center as
      NgoMIV and Cfr10I (whose crystal structures are known), and presumably also as
      EcoRII, in spite of the fact that these enzymes, which all recognize variants of
      the sequence -/CC-GG- (/ denotes the site of cleavage), are representatives of
      different subgroups of type II restriction endonucleases. A sequence comparison
      of all known restriction endonuclease sequences, furthermore, suggests that
      several enzymes recognizing other DNA sequences also share amino acid sequence
      similarities with PspGI, SsoII and EcoRII in the region of the presumptive active
      site. These results are discussed in an evolutionary context.

PMID- 12798683
TI  - Mechanism of DNA binding by the ADR1 zinc finger transcription factor as
      determined by SPR.
AB  - The ADR1 protein recognizes a six base-pair consensus DNA sequence using two zinc
      fingers and an adjacent accessory motif. Kinetic measurements were performed on
      the DNA-binding domain of ADR1 using surface plasmon resonance. Binding by ADR1
      was characterized to two known native binding sequences from the ADH2 and CTA1
      promoter regions, which differ in two of the six consensus positions. In
      addition, non-specific binding by ADR1 to a random DNA sequence was measured.
      ADR1 binds the native sites with nanomolar affinities. Remarkably, ADR1 binds non
      specific DNA with affinities only approximately tenfold lower than the native
      sequences. The specific and non-specific binding affinities are conferred mainly
      by differences in the association phase of DNA binding. The association rate for
      the complex is strongly influenced by the proximal accessory region, while the
      dissociation reaction and specificity of binding are controlled by the two zinc
      fingers. Binding kinetics of two ADR1 mutants was also examined. ADR1 containing
      an R91K mutation in the accessory region bound with similar affinity to wild
      type, but with slightly less sequence specificity. The R91K mutation was observed
      to increase binding affinity to a suboptimal sequence by decreasing the complex
      dissociation rate. L146H, a change-of-specificity mutation at the +3 position of
      the second zinc finger, bound its preferred sequence with a slightly higher
      affinity than wild-type. The L146H mutant indicates that beneficial protein-DNA
      contacts provide similar levels of stabilization to the complex, whether they are
      hydrogen-bonding or van der Waals interactions.

PMID- 12798684
TI  - Open complex formation in vitro by sigma38 (rpoS) RNA polymerase: roles for
      region 2 amino acids.
AB  - Non-functional mutants of sigma(38)(sigma(S)) were studied in vitro to identify
      the nature of their defects. Mutations in four amino acids led to severe defects
      in DNA binding and enzyme isomerization with promoter fork junction probes
      containing single-stranded non-template DNA. The same properties were previously
      seen with DNA mutations at the fork junction, implying that sigma:DNA
      interactions at the fork junction are used both for DNA binding and enzyme
      isomerization. An overlapping set of four mutants had defects that appear to be
      associated with DNA melting to create the fork junction. When mapped onto the
      sigma(70) structure, these groups of mutants suggest motifs used by sigma factors
      to melt DNA and isomerize RNA polymerase to form functional open promoter
      complexes.

PMID- 12798685
TI  - Adaptation of the Efg1p morphogenetic pathway in Candida albicans by negative
      autoregulation and PKA-dependent repression of the EFG1 gene.
AB  - The Efg1p regulator protein permits hyphal morphogenesis in the human fungal
      pathogen Candida albicans. We have identified the major promoter of the EFG1 gene
      as a direct target of Efg1p, resulting in negative autoregulation of EFG1.
      Enhanced activity of protein kinase A (PKA) isoforms Tpk1p and Tpk2p or exogenous
      overexpression of EFG1 led to Efg1p-dependent down-regulation of the endogenous
      EFG1 promoter. Serial deletion analyses of the promoter region revealed that the
      TATA box region was required for EFG1 autoregulation. By chromatin
      immunoprecipitation we detected binding of Efg1p to the EFG1 transcriptional
      initiation region. Furthermore, Sin3p, a component of a specific histone
      deacetylase complex, was shown to bind to the EFG1 promoter. sin3 mutants grew as
      budding pseudohyphae and were unable to form true hyphae, similar to strains
      constitutively expressing EFG1. We propose that the PKA signalling pathway, in
      addition to its importance in the initial steps of filament formation, is part of
      a feedback loop that controls EFG1 expression allowing continued hypha formation
      in inducing conditions. This autoregulation of EFG1 expression is probably
      mediated through the Sin3p-containing histone deacetylation complex.

PMID- 12798686
TI  - Refined model of the 10S conformation of smooth muscle myosin by cryo-electron
      microscopy 3D image reconstruction.
AB  - The actin-activated ATPase activity of smooth muscle myosin and heavy meromyosin
      (smHMM) is regulated by phosphorylation of the regulatory light chain (RLC).
      Complete regulation requires two intact myosin heads because single-headed myosin
      subfragments are always active. 2D crystalline arrays of the 10S form of intact
      myosin, which has a dephosphorylated RLC, were produced on a positively charged
      lipid monolayer and imaged in 3D at 2.0 nm resolution by cryo-electron microscopy
      of frozen, hydrated specimens. An atomic model of smooth muscle myosin was
      constructed from the X-ray structures of the smooth muscle myosin motor domain
      and essential light chain and a homology model of the RLC was produced based on
      the skeletal muscle S1 structure. The initial model of the 10S myosin, based on
      the previous reconstruction of smHMM, was subjected to real space refinement to
      obtain a quantitative fit to the density. The smHMM was likewise refined and both
      refined models reveal the same asymmetric interaction between the upper 50 kDa
      domain of the "blocked" head and parts of the catalytic, converter domains and
      the essential light chain of the "free" head observed previously. This
      observation suggests that this interaction is not simply due to crystallographic
      packing but is enforced by elements of the myosin heads. The 10S reconstruction
      shows additional alpha-helical coiled-coil not seen in the earlier smHMM
      reconstruction, but the location of one segment of S2 is the same in both.

PMID- 12798688
TI  - Analysis of insertion into secondary attachment sites by phage lambda and by int
      mutants with altered recombination specificity.
AB  - When phage lambda lysogenizes a cell that lacks the primary bacterial attachment
      site, integrase catalyzes insertion of the phage chromosome into one of many
      secondary sites. Here, we characterize the secondary sites that are preferred by
      wild-type lambda and by lambda int mutants with altered insertion specificity.
      The sequences of these secondary sites resembled that of the primary site: they
      contained two imperfect inverted repeats flanking a short spacer. The imperfect
      inverted repeats of the primary site bind integrase, while the 7 bp spacer, or
      overlap region, swaps strands with a complementary sequence in the phage
      attachment site during recombination. We found substantial sequence conservation
      in the imperfect inverted repeats of secondary sites, and nearly perfect
      conservation in the leftmost three bases of the overlap region. By contrast, the
      rightmost bases of the overlap region were much more variable. A phage with an
      altered overlap region preferred to insert into secondary sites with the
      corresponding bases. We suggest that this difference between the left and right
      segments is a result of the defined order of strand exchanges during integrase
      promoted recombination. This suggestion accounts for the unexpected segregation
      pattern of the overlap region observed after insertion into several secondary
      sites. Some of the altered specificity int mutants differed from wild-type in
      secondary site preference, but we were unable to identify simple sequence motifs
      that account for these differences. We propose that insertion into secondary
      sites is a step in the evolutionary change of phage insertion specificity and
      present a model of how this might occur.

PMID- 12798687
TI  - Crystal structure of the type II isopentenyl diphosphate:dimethylallyl
      diphosphate isomerase from Bacillus subtilis.
AB  - Two types of isopentenyl diphosphate:dimethylallyl diphosphate isomerases (IDI)
      have been characterized at present. The long known IDI-1 is only dependent on
      divalent metals for activity, whereas IDI-2 requires a metal, FMN and NADPH.
      Here, we report the first structure of an IDI-2 from Bacillus subtilis at 1.9A
      resolution in the ligand-free form and of the FMN-bound form at 2.8A resolution.
      The enzyme is an octamer that forms a D4 symmetrical open, cage-like structure.
      The monomers of 45 kDa display a classical TIM barrel fold. FMN is bound only
      with very moderate affinity and is therefore completely lost during purification.
      However, the enzyme can be reconstituted in the crystals by soaking with FMN.
      Three glycine-rich sequence stretches that are characteristic for IDI-2
      participate in FMN binding within the interior of the cage. Regions harboring
      strictly conserved residues that are implicated in substrate binding or catalysis
      remain largely disordered even in the presence of FMN.

PMID- 12798689
TI  - A low-barrier hydrogen bond between histidine of secreted phospholipase A2 and a
      transition state analog inhibitor.
AB  - This work describes in-depth NMR characterization of a unique low-barrier
      hydrogen bond (LBHB) between an active site residue from the enzyme and a bound
      inhibitor: the complex between secreted phospholipase A(2) (sPLA(2), from bee
      venom and bovine pancreas) and a transition-state analog inhibitor HK32. A
      downfield proton NMR resonance, at 17-18 ppm, was observed in the complex but not
      in the free enzyme. On the basis of site-specific mutagenesis and specific 15N
      decoupling, this downfield resonance was assigned to the active site H48, which
      is part of the catalytic dyad D99-H48. These results led to a hypothesis that the
      downfield resonance represents the proton (H(epsilon 2) of H48) involved in the H
      bonding between D99 and H48, in analogy with serine proteases. However, this was
      shown not to be the case by use of the bovine enzyme labeled with specific
      [15N(epsilon 2)]His. Instead, the downfield resonance arises from H(delta1) of
      H48, which forms a hydrogen bond with a non-bridging phosphonate oxygen of the
      inhibitor. Further studies showed that this proton displays a fractionation
      factor of 0.62(+/-0.06), and an exchange rate protection factor of >100 at 285 K
      and >40 at 298 K, which are characteristic of a LBHB. The pK(a) of the imidazole
      ring of H48 was shown to be shifted from 5.7 for the free enzyme to an apparent
      value of 9.0 in the presence of the inhibitor. These properties are very similar
      to those of the Asp em leader His LBHBs in serine proteases. Possible structural
      bases and functional consequences for the different locations of the LBHB between
      these two types of enzymes are discussed. The results also underscore the
      importance of using specific isotope labeling, rather than extrapolation of NMR
      results from other enzyme systems, to assign the downfield proton resonance to a
      specific hydrogen bond. Although our studies did not permit the strength of the
      LBHB to be accurately measured, the data do not provide support for an unusually
      strong hydrogen bond strength (i.e. >10 kcal/mol).

PMID- 12798690
TI  - Determinants of intra versus intermolecular self-association within the
      regulatory domains of Rlk and Itk.
AB  - A protein fragment from the Tec family member Rlk (also known as Txk) containing
      a single proline-rich ligand adjacent to a Src homology 3 (SH3) domain has been
      investigated by nuclear magnetic resonance (NMR) spectroscopy. Analysis of the
      concentration dependence of the chemical shifts, NMR linewidths and self
      diffusion coefficients reveal that the Rlk fragment dimerizes in solution.
      Mutation of two critical prolines in the proline-rich ligand abolishes
      dimerization. Furthermore, analysis of the extrapolated chemical shifts at
      infinite dilution reveal that intramolecular binding of the proline-rich ligand
      to the SH3 domain is disfavored. This is in contrast to the corresponding
      fragment of Itk, for which the proline-rich ligand/SH3 interaction occurs
      exclusively in an intramolecular fashion and no intermolecular binding is
      observed. Comparison of the Itk and Rlk sequences reveals that Rlk contains five
      fewer residues than Itk in the linker region between the proline-rich ligand and
      the SH3 domain. To assess whether linker length is a molecular determinant of
      intra- versus intermolecular self-association, we varied the length of the linker
      in both Rlk and Itk and analyzed the resulting variants by NMR. Intramolecular
      binding in Itk is reduced by shortening the linker and conversely a longer linker
      between the proline-rich ligand and the SH3 domain in Rlk enhances intramolecular
      self-association. Association constants for the binding of peptides corresponding
      to the proline-rich ligand with their respective SH3 domains were also measured
      by NMR. The protein/peptide data combined with the association constants for
      binding of each proline-rich peptide to the corresponding SH3 domain provide an
      explanation for the opposing modes of self-association within the otherwise
      closely related Rlk and Itk proteins.

PMID- 12798692
TI  - Membrane protein dynamics versus environment: simulations of OmpA in a micelle
      and in a bilayer.
AB  - The bacterial outer membrane protein OmpA is one of the few membrane proteins
      whose structure has been solved both by X-ray crystallography and by NMR.
      Crystals were obtained in the presence of detergent, and the NMR structure is of
      the protein in a detergent micelle. We have used 10 ns duration molecular
      dynamics simulations to compare the behaviour of OmpA in a detergent micelle and
      in a phospholipid bilayer. The dynamic fluctuations of the protein structure seem
      to be ca 1.5 times greater in the micelle environment than in the lipid bilayer.
      There are subtle differences between the nature of OmpA-detergent and OmpA-lipid
      interactions. As a consequence of the enhanced flexibility of the OmpA protein in
      the micellar environment, side-chain torsion angle changes are such as to lead to
      formation of a continuous pore through the centre of the OmpA molecule. This may
      explain the experimentally observed channel formation by OmpA.

PMID- 12798691
TI  - Mutants of protein kinase A that mimic the ATP-binding site of protein kinase B
      (AKT).
AB  - The mutation of well behaved enzymes in order to simulate less manageable
      cognates is the obvious approach to study specific features of the recalcitrant
      target. Accordingly, the prototypical protein kinase PKA serves as a model for
      many kinases, including the closely related PKB, an AGC family protein kinase now
      implicated as oncogenic in several cancers. Two residues that differ between the
      alpha isoforms of PKA and PKB at the adenine-binding site generate differing
      shapes of the binding surface and are likely to play a role in ligand
      selectivity. As the corresponding mutations in PKA, V123A would enlarge the
      adenine pocket, while L173M would alter both the shape and its electronic
      character of the adenine-binding surface. We have determined the structures of
      the corresponding double mutant (PKAB2: PKAalpha V123A, L173M) in apo and MgATP
      bound states, and observed structural alterations of a residue not previously
      involved in ATP-binding interactions: the side-chain of Q181, which in native PKA
      points away from the ATP-binding site, adopts in apo double mutant protein a new
      rotamer conformation, which places the polar groups at the hinge region in the
      ATP pocket. MgATP binding forces Q181 back to the position seen in native PKA.
      The crystal structure shows that ATP binding geometry is identical with that in
      native PKA but in this case was determined under conditions with only a single Mg
      ion ligand. Surface plasmon resonance spectroscopy studies show that significant
      energy is required for this ligand-induced transition. An additional PKA/PKB
      mutation, Q181K, corrects the defect, as shown both by the crystal structure of
      triple mutant PKAB3 (PKAalpha V123A, L173M, Q181K) and by surface plasmon
      resonance spectroscopy binding studies with ATP and three isoquinoline
      inhibitors. Thus, the triple mutant serves well as an easily crystallizable model
      for PKB inhibitor interactions. Further, the phenomenon of Q181 shows how
      crystallographic analysis should accompany mutant studies to monitor possible
      spurious structural effects.

PMID- 12798693
TI  - All, none, or some?

PMID- 12798694
TI  - Radiation therapy with and without extrafascial hysterectomy for bulky stage IB
      cervical carcinoma: a randomized trial of the Gynecologic Oncology Group.
AB  - OBJECTIVE: To evaluate, in a randomized clinical trial, the role of adjuvant
      hysterectomy after standardized radiation in improving progression-free survival
      and survival for patients with "bulky" stage IB cervical cancer. METHODS: A total
      of 256 eligible patients with exophytic or "barrel" shaped tumors measuring > or
      = 4 cm were randomized to either external and intracavitary irradiation (RT, N =
      124) or attenuated irradiation followed by extrafascial hysterectomy (RT + HYST,
      N = 132). Twenty-five percent of patients had tumors with a maximum diameter of >
      or =7 cm. RESULT: Tumor size was the most pronounced prognostic factor followed
      by performance status 2 and age at diagnosis. Hysterectomy did not increase the
      frequency of reported grade 3 and 4 adverse effects (both groups, 10%). The
      majority of these adverse effects were from the gastrointestinal or genitourinary
      tracts exclusively. There was a lower cumulative incidence of local relapse in
      the RT + HYST group (at 5 years, 27% vs. 14%). There were no statistical
      differences in outcomes between regimens except for the adjusted comparison of
      progression-free survival, although all indicated a lower risk in the adjuvant
      hysterectomy regimen (unadjusted relative risk [URR] of progression, 0.77, P =
      0.07; URR of death, P = 0.26, both one tail). CONCLUSION: Overall, there was no
      clinically important benefit with the use of extrafascial hysterectomy. However,
      there is good evidence to suggest that patients with 4-, 5-, and 6-cm tumors may
      have benefitted from extrafascial hysterectomy (URR of progression; 0.58; URR of
      death, 0.60).

PMID- 12798695
TI  - First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the
      treatment of advanced epithelial ovarian cancer patients.
AB  - OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the
      standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin
      (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with
      CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves
      long-term survival. We have therefore conducted a phase II study to evaluate the
      tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC
      patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV
      ovarian cancer who had not previously received cytotoxic drugs were treated with
      TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX
      (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six
      courses on an outpatient basis. EDX dosage was chosen after a pilot phase I
      study. RESULTS: Fifty-five patients were registered, of whom 5 were determined
      ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27
      (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response
      (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent
      a secondary debulking procedure after a median of 6 courses (range 2-6).
      Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively;
      among patients with persistent disease a successful cytoreduction (<1 cm) was
      obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0
      55.5) median progression-free survival is 19.5 months and median overall survival
      is 36 months. The most common adverse effects were G3-4 leukopenia and
      thrombocytopenia which occurred in 59 and 37% of patients, respectively.
      CONCLUSIONS: The ETC combination given according to the outlined doses and
      schedule is highly active in AOC patients with poor prognostic factors and
      deserves further study.

PMID- 12798696
TI  - Neoplastic change of squamo-columnar junction in uterine cervix and vaginal
      epithelium by exogenous estrogen in hpv-18 URR E6/E7 transgenic mice.
AB  - OBJECTIVE: The goal of this study was to study whether estrogen could induce
      progression of cervical neoplasia by the influence of direct hormonal
      transactivation of the viral genes. METHODS: We examined the in vivo effect of
      estrogen on HPV-18 URR E6/E7 transgenic mice. We analyzed the growth stimulation
      of epithelial cells at squamo-columnar junction and vagina and the expression of
      HPV E6/E7 in transgenic mice. The promoter activity of HPV-18 URR after treatment
      of estrogen was also evaluated by in vitro transient transfection assay. RESULTS:
      The dysplastic lesions of lower genital tract were more frequently seen in the
      HPV-18 URR E6/E7 transgenic mice and estrogen-treated mice, when compared to
      those of control group (P < 0.05). The majority of cells in whole epithelial
      layer of cervix and vagina were proliferating cell nuclear antigen-positive
      (PCNA) by immunohistochemical staining in the estrogen-treated transgenic mice.
      Hyperplastic glandular lesions were also identified in estrogen-treated HPV-18
      URR E6/E7 transgenic mice (5 of 21) and estrogen-treated nontransgenic mice (2 of
      10). The level of E6/E7 transcripts in transgenic mouse was increased in the
      presence of estradiol. Treatment with 0.5 x 10(-6) M estradiol in the presence of
      cotransfection with the estrogen receptor expression vector and URR-CAT showed an
      additive effect of CAT activity (4.8-fold increase). CONCLUSION: The HPV E6 and
      E7 oncogenes implicated in cervical cancer are indeed capable of potentiating
      tumor formation in animal model. Continual estrogen-induced proliferation might
      be viewed by in vivo and in vitro mechanisms by which squamous cells as well as
      glandular cells in cervix and vagina became permissive for neoplastic progression
      in HPV-18 URR E6/E7 transgenic mice and their molecular systems.

PMID- 12798697
TI  - Comparative study of primary and recurrent ovarian serous carcinomas: comparative
      genomic hybridization analysis with a potential application for prognosis.
AB  - OBJECTIVES: The purpose of this study is to comparatively characterize genomic
      imbalances in primary and recurrent ovarian serous carcinomas and to identify
      genomic alterations that may be used as a marker for prognosis. METHODS: Twenty
      ovarian serous carcinomas were studied by comparative genomic hybridization
      (CGH). RESULTS: Genomic alterations were found in all of the tumors. The most
      common regions involving gain of DNA copy numbers are 1q41q44, 8q22q24,
      19p12q13.1, 20q12q13, 3q26q29, 12p12p13, 2p22p25, 7p14p21, 5p15.2p15.3, and
      17q22q25. The most common regions with loss of DNA copy numbers are Xp11.2q13,
      4q31q35, Xp21p22.3, 18q22q23, 13q22q31, 9p22p24, and 16q22q24. High-level gains
      were detected at chromosomal regions of 1q41q44, 2p22p25, 3q26q29, and
      19p12q13.1. Comparative analysis of primary and recurrent tumors showed that
      gains of 2p22p25, 19p12q13.1, and 20q12q13 and loss of 5q14q22 were more common
      in the recurrent high-grade tumors. About 85% of the tumors showed increases in
      DNA copy numbers in the regions (2p and 8q) harboring the myc family gene.
      Patients with tumor containing fewer than seven chromosomal aberrations showed
      longer survival time. CONCLUSION: The myc oncogene family may play a role in the
      pathogenesis of ovarian serous carcinomas. Our study suggests that tumors with
      gains of 2p22p25, 19p12q13.1, and 20q12q13 and loss of 5q14q22 may be at high
      risk for recurrence. Furthermore, the patients' survival time inversely
      correlates with the numbers of chromosomal alterations found in their tumors. CGH
      analysis may have a clinical application in predicting prognosis and risk of
      recurrence in patients with ovarian serous carcinomas.

PMID- 12798698
TI  - Changes in the topological expression of markers of differentiation and apoptosis
      in defined stages of human cervical dysplasia and carcinoma.
AB  - OBJECTIVE: We compared the capacity of cells in normal cervical epithelium,
      progressive stages of CIN, and invasive carcinoma to proliferate, differentiate,
      and undergo apoptosis. METHODS: We investigated 30 conizations showing regular
      squamous epithelium of the ectocervix, all stages of cervical preinvasive
      neoplastic lesions (CIN I to III), or invasive carcinoma. The expression of the
      cell proliferation and differentiation marker Ki67 and Mad-1, respectively, and
      of the apoptosis-related proteins bcl-2, active caspase-3, and DNase I was
      analyzed on paraffin sections by immunohistochemistry. The expression of DNase I
      or -like enzymes was also analyzed at the level of their gene transcripts by in
      situ hybridization. In addition, apoptotic events were identified by in situ end
      labeling of fragmented DNA (ISEL). RESULTS: Expression of Ki67 was restricted to
      suprabasal cells in normal cervical epithelium but increased with CIN severity
      and invasive carcinoma. ISEL demonstrated apoptosis in superficial layers of
      normal, CIN I, and CIN II epithelium, whereas in CIS (CIN III) and invasive
      carcinoma, ISEL-positive cells were additionally observed at varying epithelial
      locations. Bcl-2 immunostaining remained restricted to the basal layer of all
      preneoplastic and neoplastic stages. Active caspase-3 was present in the
      suprabasal layer and extended to all upper layers in normal epithelium and
      slightly decreased with increasing dysplasia. In invasive carcinoma it was
      restricted to few scattered cells. The differentiation marker Mad-1 extended from
      the spinous to the superficial layer in regular epithelium, but gradually shifted
      to more superficial layers with increasing CIN grade and invasive carcinoma. A
      similar topological change was observed for DNase I with increasing CIN grade. In
      CIS and invasive carcinoma, DNase I immunopositive cells were solely interspersed
      within neoplastic cells. In contrast, DNase I specific mRNA was present in all
      epithelial layers in CIN III and neoplasia, suggesting a translational block of
      the expression of DNase I or -like enzymes. CONCLUSION: Our data indicate that
      the elevated proliferation observed with increasing CIN severity and carcinoma
      was not paralleled by a similar increase in cell elimination. Most of the
      dysplastic and neoplastic cervical epithelial cells appeared incapable of
      entering terminal differentiation and complete it by apoptosis, possibly due to
      their failure to express or activate apoptosis executing enzymes.

PMID- 12798699
TI  - Frequent expression of immunoreactive somatostatin receptors in cervical and
      endometrial cancer.
AB  - OBJECTIVE: A variety of human cancers has been shown to express somatostatin
      receptors which can be utilized for in vivo tumor targeting. Although the
      somatostatin receptor status of mammary and ovarian cancer has been studied in
      detail, somatostatin receptors have not been examined in other gynecological
      malignancies such as cervical or endometrial carcinoma. METHODS: We have
      previously developed a panel of somatostatin receptor subtype-specific antibodies
      that effectively stain formalin-fixed, paraffin-embedded human tumor tissue. In
      the present study, we have used these antibodies to determine the somatostatin
      receptor status of 21 randomly selected cervical carcinomas and 28 randomly
      selected endometrial carcinomas. RESULTS: In cervical carcinoma, the incidence of
      somatostatin receptor expression was sst2A (12/21, approximately 57%) > sst3
      (9/21, approximately 43%) > sst1 (8/21, approximately 38%) > sst4 (0/21, 0%) =
      sst5 (0/21, 0%). In endometrial carcinoma, the incidence of somatostatin receptor
      expression was sst3 (12/28, approximately 43%) > sst2A (11/28, approximately 39%)
      > sst1 (9/28, approximately 32%) > sst4 (1/28, approximately 4%) = sst5 (1/28,
      approximately 4%). Somatostatin receptor-like immunoreactivity was in most cases
      located at the plasma membrane and completely blocked with antigenic peptide. The
      expression of somatostatin receptor subtypes was independent of patient age,
      diagnosis, tumor stage, and histological grade. CONCLUSION: Our findings reveal a
      previously unappreciated high incidence of sst1, sst2A, and sst3 somatostatin
      receptors in human cervical and endometrial cancers and suggest that a subgroup
      of receptor-positive uterine carcinomas may be a potential target for diagnostic
      and therapeutic intervention with stable somatostatin analogs.

PMID- 12798700
TI  - Immunohistochemical expression of laminin-5 in cervical intraepithelial
      neoplasia.
AB  - OBJECTIVES: Laminin-5 is an attachment protein for epithelial cells. Several
      studies of a variety of cancers have reported increased expression of laminin-5
      in carcinoma in situ and invasive cancer. This study was designed to investigate
      the correlation between the grade of cervical intraepithelial neoplasia and the
      immunohistochemical expression of laminin-5 in the cytoplasm and in the basement
      membrane underlining dysplastic squamous cells. METHODS: We used
      immunohistochemical methods to stain paraffin-embedded sections of cervical cone
      biopsies with a monoclonal antibody specifically targeting the 2-chain of human
      laminin-5 protein. The study sample included 175 slides: 7 normal cervical
      epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81
      lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. RESULTS: We
      found a statistically significant correlation between the grade of cervical
      intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm (P <
      0.01) and in the basement membrane (P = 0.03) by use of the Wilcoxon rank-sum
      test. CONCLUSIONS: According to previously published reports we confirmed with a
      higher number of cases a correlation of laminin-5 expression in the cytoplasm
      and/or basement membrane and grade of dysplastic lesion in the cervical
      epithelium. This study warrants further investigations with special interest to
      follow-up to investigate whether laminin-5 is a marker to predict the risk of
      progression of cervical intraepithelial neoplasia lesions.

PMID- 12798701
TI  - Enhanced expression of alpha 2,6-sialyltransferase ST6Gal I in cervical squamous
      cell carcinoma.
AB  - OBJECTIVE: Increased messenger ribonucleic acid (mRNA) expression of beta
      galactoside alpha 2,6-sialyltransferase I (ST6Gal I) is important in squamous
      cell carcinoma (SCC) of the cervix. In many tissues, ST6Gal I is
      transcriptionally regulated through the use of promoters that originate in the
      mRNA species that diverge in the 5'-untranslated regions. To clarify the roles of
      ST6Gal I mRNA species in cervical SCC, we investigated their expression,
      including a "constitutive" promoter (placental or Y + Z form), "hepatic" promoter
      (H form), and a specific lymphoblastic promoter (X form), in normal and SCC
      tissues of the cervix using real-time quantitative reverse-transcription
      polymerase chain reaction (RT-PCR). METHODS: Expression of the ST6Gal I species
      was investigated in normal cervical tissue samples (n = 38) and FIGO IB1 cervical
      SCC samples (n = 38) by relatively quantitative real-time RT-PCR, using primers
      designed for amplification of a portion of the coding region common to all mRNA
      species or ones for amplification of the placental transcript, the hepatic
      transcript, or lymphoblastic transcript. RESULTS: ST6Gal I mRNA expression was
      significantly increased in cancerous tissues compared to that in normal tissues
      (P = 0.004, Mann-Whitney U test; P < 0.001, paired t test). Expression of the Y +
      Z form did not appear to be affected by cancer transformation, since it was
      detected at comparable levels in normal and cancerous tissues (P = 0.986), but H
      form expression was significantly enhanced in cancerous tissues compared to that
      in normal tissues (P < 0.001, Mann-Whitney U test and paired t test).
      Surprisingly, the X form could be detected in some patients with and without
      cancer, but the detection rate was significantly higher in patients with cancer
      (86.8% vs 52.6%, respectively; P = 0.021, Fisher's exact test). Although the X
      transcript was detected at a low level compared to the H and Y + Z transcripts,
      its expression was also significantly enhanced in patients with cancers compared
      to those without cancers (P < 0.001, Mann-Whitney U test and paired t test).
      CONCLUSIONS: An increased level of hepatic transcripts may be important in cancer
      transformation because the transcripts contribute to enhance ST6Gal I expression
      in cancerous tissues.

PMID- 12798703
TI  - Clinical relevance of Elf-1 overexpression in endometrial carcinoma.
AB  - OBJECTIVES: Elf-1 is a member of the Ets transcription factor family that
      regulates the genes involved in cellular growth and differentiation. Enhanced
      expression of Elf-1 has been reported in prostate cancer, breast cancer, and
      osteosarcoma. METHODS: To elucidate the involvement of Elf-1 in endometrial
      carcinogenesis, we analyzed serial frozen tissue sections from 31 patients with
      endometrial carcinoma and 20 patients with normal endometria for Elf-1 protein
      expression, using fluorescent immunohistochemistry. We analyzed the relationship
      between the percentages of Elf-1-stained cells and patient characteristics,
      including clinical stage, histological grade, presence of invasion to greater
      than one-half the myometrium, clinical outcome, and survival rate. RESULTS: Elf-1
      was weakly detected in some normal endometria in the proliferative phase (0
      18.9%) and other normal endometria in the secretory phase (0-28.5%). There was,
      however, abundant Elf-1 immunoreactivity in the nucleus of the endometrial
      carcinoma cells along with a little cytoplasmic staining. Scoring on the basis of
      the percentage of nuclear-positive cells indicated that nuclear Elf-1 expression
      was significantly associated with PCNA-labeling index, clinical stage,
      histological grade, the presence of invasion to greater than one-half the
      myometrium, and clinical outcome (P < 0.01, respectively). Survival data were
      available for all patients and demonstrated that Elf-1 expression was
      significantly associated with poor prognosis (P < 0.01). CONCLUSIONS: Our results
      demonstrate that Elf-1 expression in endometrial carcinoma correlates with the
      malignant potential of this tumor.

PMID- 12798702
TI  - Phase II clinical study of irinotecan and cisplatin as first-line chemotherapy in
      metastatic or recurrent cervical cancer.
AB  - OBJECTIVE: The goal of this study was to evaluate the efficacy and tolerability
      of irinotecan plus cisplatin as first-line chemotherapy in metastatic or
      recurrent cervical cancer. METHODS: Chemotherapy-naive patients with metastatic
      or recurrent disease and at least one measurable tumor site received irinotecan
      (60 mg/m(2) IV infusion over 90 min) on Days 1, 8, and 15, followed by cisplatin
      (60 mg/m(2) IV over 90 min) on Day 1, every 28 days for a maximum of six cycles.
      RESULTS: Thirty patients were included in the response and toxicity analysis. The
      median age was 45 years (34-65). Nineteen patients had metastatic disease, 6
      presented with locally recurrent disease, and 5 presented with locally recurrent
      plus metastatic disease. Seven patients were stage IVB at diagnosis. There were 2
      complete and 18 partial responses and overall response rate was 66.7% (95%
      confidence interval: 47-85%). Stable disease was observed in 2 patients (6.7%)
      and progression in 8 (26.7%). Median time to relapse was 13.4 months, with a
      median survival time of 16.9 months. One-year disease-free survival and overall
      survival were 26.7 and 65.1%, respectively. Dose-limiting toxicity was observed
      in 4 patients (13.3%) with grade 3 renal toxicity. Nine patients (30%) developed
      grade 3 neutropenia, and only grade 1-2 acute and late diarrhea were observed in
      20 and 40%, respectively. A patient developed pancolitis after the sixth cycle.
      There were no chemotherapy-related deaths. CONCLUSION: The combination of
      irinotecan and cisplatin is a clinically active regimen for metastatic and/or
      recurrent cervical cancer with acceptable tolerability.

PMID- 12798704
TI  - Platelet-derived endothelial cell growth factor as a prognostic factor for
      radiotherapy outcome in patients with adenocarcinoma of the uterine cervix.
AB  - OBJECTIVE: The aim of this study was to evaluate the platelet-derived endothelial
      cell growth factor (PD-ECGF) and VEGF expressions of tumor cells as prognostic
      factors for radiotherapy outcome in patients with adenocarcinoma of the uterine
      cervix. METHODS: In 47 formalin fixed, paraffin-embedded tissues from
      adenocarcinoma of the uterine cervix which had been treated with radiation (1970
      1995), PD-ECGF and VEGF expressions were determined using immunohistochemistry,
      and the relationships between PD-ECGF or VEGF expressions and local control or
      survival were assessed. RESULTS: PD-ECGF and VEGF expressions were successfully
      detected in the cytoplasm and/or nucleus of adenocarcinoma cells of the uterine
      cervix. Of the 47 patients, 44.6 (21/47 cases) and 57.4% (27/47 cases) were
      positive for PD-ECGF and VEGF, respectively. There was no correlation between PD
      ECGF or VEGF expressions and age, grade, or histologic subtypes. Stage and high
      expression of PD-ECGF showed a significant correlation to local control (P =
      0.0025, P = 0.0057, respectively) and were significant independent prognostic
      factors for 5-year survival in multivariate analysis (P = 0.0039, P = 0.0032,
      respectively). CONCLUSION: This study demonstrated that PD-ECGF expression was a
      significant prognostic factor for radiotherapy outcome in patients with
      adenocarcinoma of the uterine cervix. Preradiation assessment of PD-ECGF
      expression may be helpful in selecting high-risk patients, providing them with
      opportunities to receive more sophisticated and individualized treatments.

PMID- 12798705
TI  - Evaluation of low-dose intraperitoneal interferon-alpha for palliation of ascites
      in patients with non-ovarian gynecologic malignancies.
AB  - OBJECTIVE: Intraperitoneal interferon-alpha (IP-IFNalpha) has shown some benefit
      in the treatment of patients with ovarian cancer. Our goal was to evaluate the
      use of low-dose IP-IFNalpha for the palliative control of ascites in non-ovarian
      gynecologic malignancies, including primary peritoneal and uterine papillary
      serous carcinomas. METHODS: Fifteen patients with non-ovarian gynecologic
      malignancies received one or two doses of 10 MU (10 x 10(6) U/m(2)) of IP
      IFNalpha via single-use drum catheter for the symptomatic control of ascites. The
      median age for this patient group was 61 years (range 40-84). Histopathologic
      diagnoses were confirmed on all patients. Eleven of 15 (73%) patients had uterine
      cancers. Four of 15 (27%) patients had papillary serous primary peritoneal
      carcinomas. Thirteen of 15 (87%) patients had Stage III disease or more. All
      patients had been heavily pretreated with chemotherapy and all had progressive
      disease. RESULTS: Specific parameters used to evaluate IP-IFNalpha were (1)
      median survival; (2) number of days to recurrent ascites; (3) number of
      subsequent paracenteses required for symptomatic relief; and (4) symptomatology
      and side effects. Median overall survival was 3 months (range 0.5-13). Seven of
      15 (47%) patients survived >3 months. Twelve of 15 (80%) patients had recurrent
      ascites within 30 days of treatment. However, 3/15 (20%) patients had a
      prolonged, >30-day period, without symptomatic ascites. One patient (6%) had a
      270-day response with no ascites. Toxicity was minimal from IP-IFNalpha infusion.
      The most common side effect was fever in 6/15 (40%) patients. CONCLUSION: IP
      IFNalpha was well tolerated and may have some benefit in a subset of patients.
      Although 80% of patients had recurrent ascites within 30 days, 20% had a
      prolonged, >30-day response. Further study is warranted to determine the role of
      immune modulators, such as IP-IFNalpha, in the palliative management of patients
      with non-ovarian gynecologic malignancies that cause ascites.

PMID- 12798706
TI  - Strength of correlations between colposcopic impression and biopsy histology.
AB  - OBJECTIVE: The aim of this study was to determine the strength of the correlation
      between colposcopic impression and biopsy histology. METHODS: In an urban
      referral clinic, colposcopy and directed biopsy were performed between July 1,
      1996, and December 31, 1999, by residents supervised by board-certified attending
      obstetrician-gynecologists. Impression and biopsy were graded as benign,
      suggesting condyloma or koilocytosis, cervical intraepithelial neoplasia (CIN)
      grades 1-3, or cancer. The significance of association was assessed by chi(2)
      testing and the strength by kappa statistics. RESULTS: Colposcopies were
      performed on 2825 women, with colposcopic impression and biopsy grade known for
      2112. Exact agreement was found in only 893 (37%) women, but results agreed
      within one grade in 1203 (75%). The association between impression and histology
      was significant (P < 0.001), but the strength of the correlation was poor (0.20).
      The positive predictive value of any colposcopic abnormality for any histologic
      abnormality was 80%. The negative predictive value of a benign colposcopic
      impression was 68%. The sensitivity of colposcopy with a threshold of any lesion
      detected was 89%, and the specificity was 52%. The sensitivity for CIN 2/3 was
      56%. CONCLUSION: Colposcopy is imprecise, although useful in estimating lesion
      grade. Management decisions require biopsy.

PMID- 12798707
TI  - Successful administration of carboplatin in patients with clinically documented
      carboplatin hypersensitivity.
AB  - OBJECTIVE: The goal of this study was to evaluate the tolerance and effectiveness
      of carboplatin rechallenge using a prolonged desensitizing carboplatin infusion
      regimen in patients with clinically documented moderate-severe carboplatin
      hypersensitivity. METHOD: Patients admitted for carboplatin infusion were
      identified by computerized pharmacy records and retrospectively analyzed. RESULT:
      Thirty-three patients with recurrent ovarian (N = 27), peritoneal (N = 4), tubal
      (N = 1), and cervical (N = 1) cancer treated with a prolonged desensitizing
      carboplatin infusion regimen were identified. The patients had received a median
      of 10 courses of carboplatin (range 3-33) before developing the moderate-severe
      hypersensitivity reaction. Two hundred and fifteen courses (median 5, range 1-52)
      were administered. Twenty-nine patients (88%) were successfully rechallenged
      while four had a recurrent moderate-severe carboplatin hypersensitivity
      precluding further administration. Despite initial tolerance of the infusion
      schedule moderate-severe carboplatin hypersensitivity recurred in 3 additional
      patients (9%) after two, three, and six subsequent courses. Objective responses
      to therapy were seen in 22 of 28 evaluable patients (79%). CONCLUSIONS: A
      prolonged desensitizing carboplatin infusion regimen is tolerated in the majority
      of patients with clinically documented moderate-severe carboplatin
      hypersensitivity. Objective response rates seem acceptable with this schedule.

PMID- 12798708
TI  - The role of microsatellite instability in cervical intraepithelial neoplasia and
      squamous cell carcinoma of the cervix.
AB  - OBJECTIVES: This study was conducted to define the role of microsatellite
      instability (MSI) in cervical intraepithelial neoplasia (CIN) and squamous cell
      carcinoma (SCC) of the cervix. We also tested the validity of using markers
      recommended for MSI study in colonic carcinoma by the National Cancer Institute
      (NCI) for cervical neoplasm. METHODS: Twenty normal cervical, 24 low-grade CIN
      (CIN-L), 59 high-grade CIN (CIN-H), and 93 SCC tissues were examined for MSI
      after microdissection. A polymerase chain reaction based MSI detection was
      performed using five markers recommended by the NCI for colonic cancer (panel
      one) as well as five other markers (panel two) found to be informative in earlier
      studies. High-frequency MSI (MSI-H) was defined as instability in > or = 2 of 5
      loci if one panel was used and > or = 30% of loci when more than five loci were
      used. Low-frequency MSI (MSI-L) was diagnosed if instability was noted but did
      not meet the criteria of MSI-H. Findings were correlated with clinicopathologic
      information. RESULTS: The combined use of panel one and two markers showed no MSI
      in normal cervical or CIN-L tissue, MSI-L in 1 CIN-H (1.7%), MSI-L in 16 (17.2%),
      and MSI-H in 11 (11.8%) SCC, respectively. The NCI-recommended panel alone
      detected 19 of 27 MSI-positive SCC. MSI-positive was not related to patient age,
      disease stage, and tumor grade. The overall survival of MSI-positive patients was
      significantly worse than that of microsatellite stable patients (P = 0.02). An
      increasing trend of MSI-H rate with higher disease stages was noted (P = 0.035)
      but MSI-H was not associated with poor prognosis. CONCLUSIONS: The NCI
      recommended panel of markers might not be useful in MSI study for SCC and using
      more than five markers improves the MSI detection. MSI is rare in cervical
      dysplasia but is present in a subset of SCC. The association between MSI
      positivity and prognosis awaits future confirmation.

PMID- 12798709
TI  - Pre- and postmenopausal high-risk women undergoing screening for ovarian cancer:
      anxiety, risk perceptions, and quality of life.
AB  - OBJECTIVE: Recommendations for women at high risk of ovarian cancer include
      prophylactic salpingo-oophorectomy (PSO) or screening with transvaginal
      ultrasonography (TVUS) and CA125 levels. The best strategy for improving survival
      and maintaining quality of life in high-risk women is not known. Premenopausal
      women may be more reluctant than postmenopausal women to undergo PSO. However,
      the risk of false-positive screening results may be more likely in premenopausal
      women, posing potential psychological risk for those enrolled in high-risk
      ovarian cancer surveillance programs. We sought to determine whether anxiety,
      depression, perception of ovarian cancer risk, and false-positive test frequency
      differed between high-risk premenopausal and postmenopausal women initiating
      ovarian cancer screening. METHODS: High-risk women aged > or = 30 years enrolling
      in a TVUS plus CA125 ovarian cancer screening study completed standard QOL (SF
      36), cancer-specific anxiety (IES), depression (CES-D), and ovarian cancer risk
      perception measures. CA125 > 35 and TVUS showing solid or complex cystic ovarian
      masses were considered abnormal. Abnormal tests were repeated after 4-6 weeks.
      Persistently abnormal tests prompted a search for malignancy. Tests that
      normalized on repeat were considered false positive. RESULTS: One hundred forty
      seven high-risk women, median age 46 (range, 30-78), 78 premenopausal and 69
      postmenopausal, had > or = 1 TVUS/CA125/outcome assessment. Premenopausal women
      were more likely than postmenopausal women to consider themselves at higher risk
      of ovarian cancer compared with women their age (P < 0.001) and compared with
      women with similar family histories (P < 0.001). Mean personal perception of
      lifetime risk of ovarian cancer among premenopausal women was 37% (range, 0-90%)
      versus 26% (range, 0-60%) among postmenopausal women (P = 0.02). While general
      QOL and depression scores were similar, 38% of premenopausal women reported high
      anxiety versus 27% of postmenopausal women (P = 0.03). Thirty percent of women
      required repeat CA125 or TVUS after first screening; 10.8% of premenopausal women
      versus 4.6% of postmenopausal women required repeat CA125; and 23.3% of
      premenopausal and 20.6% of postmenopausal women required repeat TVUS. One
      postmenopausal woman with persistently rising CA125 >100 had negative
      mammography, colonoscopy, and dilation and curettage/bilateral salpingo
      oophorectomy. All other abnormal tests normalized on repeat. Two premenopausal
      women withdrew due to anxiety following false-positive CA125 results. Five women
      (2 premenopausal, 3 postmenopausal) with normal TVUS/CA125 screening tests
      elected PSO, with benign findings. CONCLUSION: Premenopausal women perceive their
      ovarian cancer risk to be higher, report greater ovarian cancer risk-related
      anxiety, and are more likely to have false-positive screening results than
      postmenopausal women. Few high-risk women elect PSO in the short term. Knowledge
      of the frequency of false-positive screening results and psychosocial outcomes is
      important for high-risk women choosing strategies for managing ovarian cancer
      risk.

PMID- 12798710
TI  - Comparison of the usefulness between a new universal grading system for
      epithelial ovarian cancer and the FIGO grading system.
AB  - OBJECTIVE: The aim of this study was to compare the usefulness of a new universal
      grading system for ovarian cancer proposed by Shimizu et al. (Cancer 82 (1998),
      893; Gynecol. Oncol. 70 (1998), 2) with that of the FIGO grading system as a
      prognostic factor of ovarian cancer. METHODS: We reviewed all paraffin-embedded
      tissues of epithelial ovarian cancer obtained from 130 women who underwent
      initial treatment including primary surgery in our hospital between January 1990
      and December 2000. The scores of the specimens were obtained according to both
      the universal grading system and the FIGO grading system. RESULTS: Both the FIGO
      grading system and the universal grading system worked as significant prognostic
      indicators. Patients with Grades 1 and 3 of the universal grading system had high
      and low 5-year survival rates, respectively, compared to those of the FIGO
      grading system. Inconsistencies in histologic grade between the FIGO and
      universal grading systems were observed in 22 patients. The positive rate of
      lymph node metastasis in patients with Grade 3 of the universal grading system
      was significantly high compared to those of the FIGO grading system (P = 0.03).
      Patients with Grade 3 of the universal grading system with residual tumor of not
      less than 2 cm in diameter were observed more frequently than those of the FIGO
      grading system. C4ONCLUSION: The universal grading system was superior to the
      FIGO grading system in terms of the prediction of malignancies such as the
      potential of lymph node metastasis and invasion and the adaptability to clear
      cell cancer.

PMID- 12798711
TI  - Expression of matrix metalloproteinase-26 and tissue inhibitors of
      metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and their physiological inhibitors,
      the tissue inhibitors of MMPs (TIMPs), play a key role in tumor cell invasion,
      angiogenesis, and growth. The aim of this study was to determine the expression
      and cellular distribution of MMP-26, TIMP-3, and TIMP-4 in endometrial cancers
      and benign endometrium throughout the menstrual cycle and the correlation with
      tumor histological subtype, stage, and grade. METHODS: Immunohistochemical
      analysis using polyclonal antibodies generated against pro- and active MMP-26,
      and mono- and polyclonal antibodies specific to TIMP-3 and TIMP-4, respectively,
      was performed. RESULTS: MMP-26, TIMP-3, and TIMP-4 are expressed in endometrial
      carcinomas (N = 86) and benign endometrium (N = 50) from various stages of the
      menstrual cycle. Semi-quantitative analysis of staining intensity indicated that
      endometrial carcinomas expressed more MMP-26, TIMP-3, and TIMP-4 compared to
      benign endometrium from the postmenopausal period, but not from the secretory
      phase of the menstrual cycle. The highest staining intensity was associated with
      endometrial epithelial cells, followed by vascular endothelial cells, myometrial
      smooth muscle cells, and endometrial stromal cells. Increased staining intensity
      of MMP-26 and TIMP-3 correlated with grade III tumors and MMP-26 and TIMP-4 with
      the depth of myometrial invasion in tumors histologically characterized as
      endometrioid adenocarcinoma, clear-cell, and papillary serous carcinoma
      staged/graded based on FIGO criteria. CONCLUSION: MMP-26 and TIMP-4 are expressed
      in endometrium and endometrial carcinoma and their elevated expression and
      correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a
      key role in endometrial tumor progression.

PMID- 12798712
TI  - Retrospective review of 208 patients with leiomyosarcoma of the uterus:
      prognostic indicators, surgical management, and adjuvant therapy.
AB  - OBJECTIVE: We evaluated the predictive value of several proposed prognostic
      indicators and the effect of surgical management and adjuvant therapy on clinical
      outcome associated with leiomyosarcoma (LMS) of the uterus. METHODS: A medical
      record search of patients treated at Mayo Clinic from 1976 through 1999 was
      performed using the International Classification of Diseases, Ninth Revision
      codes for LMS and malignant neoplasm of the uterus. Study inclusion criteria
      included confirmation of the diagnosis of LMS of the uterus by a pathologist at
      our institution. Survival curves were generated using the Kaplan-Meier method.
      Multivariate analysis was performed using the Cox proportional hazards model. A
      case-control investigation was also performed. RESULTS: A total of 208 patients
      met study requirements. The median follow-up for survivors was 7.7 years.
      Multivariate analysis showed that high grade, advanced stage, and oophorectomy
      were associated with significantly worse disease-specific survival. Case-control
      investigations suggested that ovarian preservation does not adversely affect
      survival and that adjuvant pelvic radiation therapy does not significantly
      improve survival. An LMS risk-assessment index that was generated is highly
      predictive of survival. CONCLUSION: Tumor grade and stage (using modified
      criteria for endometrial cancer) appear to be valid prognostic indicators for LMS
      of the uterus. Ovarian preservation may be considered in premenopausal patients
      with early-stage leiomyosarcoma of the uterus. Additionally, adjuvant therapy
      does not appear to significantly affect survival. Finally, our highly predictive
      LMS risk-assessment index may be useful for counseling patients.

PMID- 12798713
TI  - Phase II trial of danazol in advanced, recurrent, or persistent endometrial
      cancer: a Gynecologic Oncology Group study.
AB  - OBJECTIVES: To evaluate the activity and toxicity of danazol in advanced,
      recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with
      advanced, recurrent, or persistent endometrial carcinoma not amenable to curative
      therapy were treated with danazol at a dose of 100 mg four times per day until
      disease progression or toxicity necessitated discontinuation. Eligibility
      criteria included the presence of measurable disease and no prior chemotherapy.
      Immunohistochemical analysis of metastatic tumor tissue for estrogen and
      progesterone receptors was required. RESULTS: Twenty-five patients were enrolled
      and 3 were excluded. Six patients had tumors staining positive for both estrogen
      and progesterone receptors. There were no responders among 22 eligible patients.
      Six patients (27%) demonstrated stable disease as their best response. The median
      progression-free survival and overall survival were 1.9 and 14.4 months,
      respectively. A median total dose of 21.7 (range: 1.4 to 67.2) of danazol was
      administered. Therapy was discontinued in 5 eligible patients due to toxicity.
      Four of these patients experienced hepatic toxicity. CONCLUSIONS: Danazol has
      minimal activity in advanced, recurrent, or persistent endometrial carcinoma.

PMID- 12798714
TI  - Sentinel node identification and the ability to detect metastatic tumor to
      inguinal lymph nodes in squamous cell cancer of the vulva.
AB  - OBJECTIVES: The goal of this study was to identify one or more inguinal sentinel
      nodes in patients with primary squamous cell carcinoma of the vulva and to
      determine the ability of the sentinel node to predict metastasis to the inguinal
      lymphatic basin. METHODS: Techniques employing technetium-99m (Tc-99m) sulfur
      colloid and isosulfan blue dye were utilized to identify sentinel nodes in the
      inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally
      at the tumor margins 90-180 min preoperatively followed by a similar injection of
      isosulfan blue dye 5-10 min before the groin dissection. A handheld collimated
      gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic
      tracts that had taken up blue dye and their corresponding sentinel node were also
      identified and retrieved. A completion inguinal dissection was then performed.
      Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and
      blue. The sentinel nodes were subjected to pathologic examination with step
      sections and nonsentinel nodes were evaluated in the standard fashion. RESULTS:
      Twenty-one patients with a median age of 79 were entered onto protocol and a
      total of 31 inguinal node dissections were performed. A sentinel node was
      identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan
      blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical
      staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with
      stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin
      dissections were found to have metastatic disease, and in 4 of these dissections,
      the sentinel node was the only positive node. Lymph nodes in 22 groin dissections
      had no evidence of metastasis. No false-negative sentinel lymph nodes were
      obtained (sentinel node negative and a nonsentinel node positive). CONCLUSION: Tc
      99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel
      nodes in inguinal dissections of patients with vulvar cancer. A sentinel node
      dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal
      dissections. Pathologic examination with step sections has shown the sentinel
      node to be an accurate predictor of metastatic disease to the inguinal nodal
      chain.

PMID- 12798715
TI  - Detection of epidermal growth factor receptor mRNA in peripheral blood of
      cervical cancer patients.
AB  - OBJECTIVE: Epidermal growth factor receptor (EGFR) has been reported to be
      expressed by immunohistochemistry in invasive cervical cancers. We evaluated the
      feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase
      chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer.
      METHODS: Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was
      examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines
      expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines
      expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45
      cervical cancer patients were also examined. RESULTS: In peripheral blood from 20
      healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA
      was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45
      (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control).
      On the other hand, expression of EGFR was observed in 98% of tumor tissues by
      immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%)
      and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control).
      The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage
      (P = 0.049). CONCLUSION: Both CK-19 mRNA and CK-20 mRNA showed no diagnostic
      value as markers of circulating tumor cells in cervical cancers. However, EGFR
      mRNA in blood might be a useful marker of circulating tumor cells in cervical
      cancers.

PMID- 12798716
TI  - Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy
      for patients with high-risk epithelial tumors of mullerian origin.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of combining
      docetaxel, carboplatin, and gemcitabine (DoCaGem) as first-line treatment of
      ovarian and other mullerian origin tumors. METHODS: Four dose levels were planned
      for this phase I trial. Treatment consisted of carboplatin on day 1 only,
      docetaxel on days 1 and 8, and gemcitabine on days 1 and 8, every 21 days.
      RESULTS: Nineteen patients were enrolled, of whom 18 were evaluable for toxicity.
      The first 5 patients enrolled at dose level I (carboplatin AUC 5, 30 mg/m(2)
      docetaxel, 800 mg/m(2) gemcitabine) experienced no dose-limiting toxicity. At
      dose level II, 4/4 evaluable patients experienced significant bone marrow
      suppression that required dose reduction and/or dose delay. Further dose
      escalation was not attempted, and 9 additional patients were enrolled in dose
      level I. Of the 67 cycles administered on dose level I, day 8 treatment could not
      be administered due to bone marrow suppression in 16 cycles (24%), and
      prolongation of the cycle length from day 22 to day 29 was required in 13 cycles
      (19%). There were no episodes of febrile neutropenia in evaluable patients and no
      treatment-related deaths. Grade 3 nonhematologic toxicity (fatigue) occurred in 1
      cycle. Response was determined in the 14 evaluable patients who tolerated 4 or
      more cycles of therapy, with 11 obtaining a complete clinical response and 3
      obtaining a partial clinical response. CONCLUSIONS: The DoCaGem regimen is highly
      active, but myelosuppression at dose level I prevents full dose delivery. Other
      strategies to combine these three active agents are reasonable to explore.

PMID- 12798717
TI  - Population attributes affecting the prevalence of BRCA mutation carriers in
      epithelial ovarian cancer cases in israel.
AB  - OBJECTIVE: The objective was to evaluate the prevalence of BRCA1/2 mutations in
      selected categories of ovarian cancer patients in Israel. METHODS: Blood samples
      and specimens of ovarian tumors were obtained in the course of a national case
      control study of women with ovarian cancer in Israel. Eight hundred ninety-six
      patients with epithelial ovarian cancer, 40 cases with nonepithelial ovarian
      cancer, and 68 with primary peritoneal cancer were tested for the BRCA mutations.
      Analysis of the three common BRCA mutations in Israel (185delAG, 5382insC in
      BRCA1, and 6174delT in BRCA2) was done using a multiplex polymerase chain
      reaction assay. A multivariate logistic regression model was used to assess the
      association of mutation carrier status and other factors (age, origin, family
      history, and clinical variables). RESULTS: Of the 779 invasive epithelial ovarian
      cancer cases, 29.4% were mutation carriers. The prevalence of the mutations was
      higher among women below age 60 and in more advanced cases. The prevalence was
      low in mucinous tumors. There was almost a twofold excess of mutations among
      women with positive family history (45.7%), but still 26.5% of the family history
      negative cases were carriers. As expected, we found a higher rate of mutation
      carriers among the Ashkenazi group (34.2%) and 55% among Ashkenazi women with
      positive family history. No subjects born in North Africa were mutation positive.
      CONCLUSION: BRCA mutations are strongly associated with ovarian cancer and they
      are present in variable rates in distinct age, ethnic, and histopathologic
      categories.

PMID- 12798718
TI  - Concurrent carboplatin with pelvic radiation therapy in the primary treatment of
      cervix cancer.
AB  - OBJECTIVES: The objectives were to determine the acute toxicities of concurrent
      carboplatin and radiation therapy in the primary treatment of cervix cancer and
      to ascertain the antitumor activity of this regimen. METHODS: Patients with stage
      IB-1 to IVA untreated primary cervix cancers were eligible for enrollment into
      this study. Carboplatin was administered on a weekly basis with external
      radiation therapy (ERT). Low-dose brachytherapy was given after completion of
      ERT. Acute toxicities and response to treatment were assessed. RESULTS: Thirty
      one evaluable patients were enrolled. The majority of patients had early stage
      disease. Carboplatin was successfully administered in 175 out of 186 (94%)
      planned treatments. All patients completed the prescribed course of radiation
      therapy. The mean treatment time was 50 days (36-73). There were no treatment
      delays for neutropenia or gastrointestinal toxicity. No patient was hospitalized
      for treatment related toxicities. Gastrointestinal toxicity equivalent to grade 3
      or 4 was not reported. The objective tumor response based on physical exam
      findings and computed tomography measurements was 90%. CONCLUSION: Patients with
      cervix cancer can be treated on schedule with concurrent carboplatin and pelvic
      radiation therapy. This regimen is well tolerated and produces excellent response
      rates.

PMID- 12798719
TI  - Transperitoneal laparoscopic pelvic and para-aortic lymph node dissection using
      the argon-beam coagulator and monopolar instruments: an 8-year study and
      description of technique.
AB  - OBJECTIVE: The objective was to describe the results, technique, and
      complications of transperitoneal laparoscopic (LSC) pelvic and aortic lymph node
      dissection (LND) using the argon-beam coagulator (ABC) and monopolar
      electrosurgical instruments in women with gynecologic malignancies. METHODS: A
      retrospective chart review of 114 patients who underwent LSC pelvic and/or aortic
      LND in addition to other LSC procedures between 1/1994 and 12/2001 was conducted.
      All intraoperative complications and complications that occurred within the first
      30 postoperative days were included. Complications were graded according to an
      institutional surgical secondary events reference. During the same time period,
      89 patients underwent LSC followed immediately by laparotomy that included LND,
      resulting in a total of 203 cases. These 203 total cases are used as a
      denominator to determine the etiology of cases converted from LSC to laparotomy.
      Monopolar electrosurgical instruments or the 10-mm ABC (Conmed) set at 70 W with
      argon flow of 3-4 L/m min were used for laparoscopic nodal dissection. RESULTS:
      Sixty-one of 114 (53%) patients underwent pelvic LND, 35 (31%) underwent both
      pelvic and aortic LND, and 18 (16%) underwent aortic LND only. Mean patient age
      and body mass index were 53.3 years (range, 16 to 87 years) and 25 (range, 16 to
      40), respectively. In addition, the mean number of pelvic and aortic lymph nodes
      removed was 10.7 (range, 1 to 39) and 5.7 (range, 0 to 21), respectively. The
      mean estimated blood loss was 151 mL (range, 25 to 600 ml) and the mean hospital
      stay was 2.8 days (range, 0 to 35 days). Overall, complications occurred in eight
      (7%) cases. There were no fatal complications, and no patient required conversion
      to laparotomy due to uncontrollable bleeding from the laparoscopic nodal
      dissection. Only 17 of 203 (8%) patients required conversion to laparotomy
      secondary to adhesions and unsatisfactory exposure. CONCLUSION: Laparoscopic
      pelvic and aortic LND for gynecologic malignancies can be satisfactorily
      performed in the majority of patients, with only 8% of patients requiring
      conversion to laparotomy due to adhesions or unsatisfactory exposure. The overall
      complication rate was 7% and was limited to grade 3 or less.

PMID- 12798720
TI  - Relationship between a history of systemic allergic reactions and risk of
      subsequent carboplatin hypersensitivity.
AB  - OBJECTIVE: The establishment of clinical features identifying patients at a
      heightened risk for the development of carboplatin hypersensitivity may assist in
      the management of this important toxicity. Based on a previous report suggesting
      a history of "bee sting" allergy predicted for paclitaxel hypersensitivity, we
      attempted to determine if there was a relationship between a history of prior
      systemic allergic reactions and the subsequent development of carboplatin
      hypersensitivity. PATIENTS AND METHODS: The medical records of all women treated
      in the Gynecologic Cancer Program of the Cleveland Clinic from June 1995 to May
      2002 who received >6 cycles of platinum-based chemotherapy were retrospectively
      reviewed for a history of prior systemic hypersensitivity (e.g., medications,
      environmental exposure). The incidence of "positive" allergic histories was then
      examined in relation to the subsequent risk of patients developing either a
      documented carboplatin hypersensitivity reaction or a "positive" carboplatin skin
      test. RESULTS: The analysis included 174 patients (91 undergoing "carboplatin
      skin testing") who received > 6 courses of carboplatin. Of 53 patients with no
      recorded history of systemic hypersensitivity treated prior to our routine use of
      carboplatin skin testing, 19% experienced an allergic reaction, in contrast to a
      40% incidence of a documented carboplatin reaction in 30 patients with a recorded
      history of hypersensitivity to a medication or environmental exposure (P < 0.05).
      For the 55 patients with no history of systemic hypersensitivity who underwent
      carboplatin skin-testing, 27% had a positive test result, in comparison to a 36%
      positive test rate in women with a previous history of a systemic
      hypersensitivity reaction recorded in the medical record (P > 0.05). CONCLUSION:
      This analysis suggests that patients with a prior history of systemic
      hypersensitivity to medications or environmental exposures may be at a heightened
      risk for experiencing allergic reactions to carboplatin.

PMID- 12798721
TI  - The use of MRI in the diagnosis and management of a bulky cervical carcinoma.
AB  - BACKGROUND: In the treatment of gynecologic cancer, surgical planning depends on
      the site and extent of disease. The evaluation of the origin of a large pelvic
      mass with combined pelvic examination and ultrasound is often adequate. However,
      the following case report illustrates the utility of magnetic resonance imaging
      (MRI) when sonographic findings are indeterminate and the origin of a pelvic mass
      is unclear. CASE: A 73-year-old woman presented for her first gynecologic exam in
      over 40 years. On speculum examination the cervix was not visible. A large,
      mobile pelvic mass was palpated during physical examination. Pelvic ultrasound
      revealed a large, cystic pelvic mass thought to be ovarian in origin. Surgery for
      presumed ovarian carcinoma was planned. Because a vaginal Pap smear revealed
      squamous-cell carcinoma, MRI was performed for further evaluation. MRI
      demonstrated a blood distended uterus with a large cervical tumor obstructing the
      endocervical os. After cervical dilatation under sonographic guidance, evacuation
      of the hematometrium was performed. Multiple biopsies of the cervix confirmed the
      diagnosis of a bulky Stage IIA squamous-cell carcinoma of the cervix. The patient
      was subsequently treated with concomitant chemotherapy and radiation therapy.
      Follow-up MRI demonstrated an excellent treatment response. Modified radical
      hysterectomy was performed demonstrating very small residual tumor. CONCLUSIONS:
      Magnetic resonance imaging, through multiplanar capabilities and high-contrast
      resolution, is a valuable tool that can assist the clinician in the evaluation,
      diagnosis, and management of challenging gynecologic malignancies.

PMID- 12798722
TI  - Oral squamous carcinoma in a patient with cervix cancer: use of human
      papillomavirus analysis to differentiate synchronous versus metastatic tumor.
AB  - BACKGROUND: Cervical cancer usually spreads by direct infiltration and
      disseminates by lymphatic and hematogenous pathways. The common sites of distant
      metastases are the lungs, liver, and bones. Other rare metastatic sites have been
      previously described including only one case of oral cavity metastasis. CASE: We
      present here the second case of a patient with apparent oral cavity metastasis
      from cervical cancer. By cloning specific human papilloma virus (HPV) genomic
      regions, the two lesions showed HPV genomic sequences from different viruses (18
      and 33, for the uterine cervix and the oral cavity, respectively), thus
      indicating the oral lesion as a synchronous second primary tumor. CONCLUSION: The
      use of molecular markers to distinguish between a secondary and a primary lesion
      is recommendable in cervical cancer, particularly when reporting rare site
      metastases.

PMID- 12798723
TI  - Squamous cell carcinoma arising in a dermoid cyst of the ovary.
AB  - BACKGROUND: Unlike ordinary germ cell tumors of the ovary, squamous cell
      carcinoma arising in a dermoid affects elderly persons. Prognosis is poor when
      the disease has spread beyond the ovary. CASE: The case of a 67-year-old woman
      with stage III squamous cell carcinoma arising in a dermoid cyst of the ovary and
      extending to the serosa and myometrium of the uterus, pelvic peritoneum, the
      serosa, and muscularis of the distal ileum and penetrating entirely through the
      wall of the sigmoid is presented. She underwent total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, omentectomy, partial small bowel resection with
      anastomosis, partial colectomy with anastomosis, and excision of tumor from the
      pelvic peritoneum. She was treated with six cycles of Taxol and cisplatin
      chemotherapy at monthly intervals. She has remained disease-free for over 4
      years. CONCLUSION: This is the fourth report of a prolonged disease-free survival
      of a patient with stage III squamous cell carcinoma arising in a dermoid cyst of
      the ovary. This result is encouraging, but the best treatment for advanced cancer
      of this type has yet to be determined.

PMID- 12798724
TI  - Contralateral groin node metastasis following ipsilateral groin node dissection
      in vulval cancer: a case report.
AB  - BACKGROUND: The majority of vulval cancers are of the squamous cell type. Current
      operative management strategies are based on modifications of radical vulvectomy
      and groin node dissection, enabling a more individualised and conservative
      approach to surgery. This has led to interesting dilemmas regarding the most
      appropriate management in certain individuals. CASE: We describe a case of a
      contralateral recurrence following unilateral groin node dissection for vulval
      cancer, with an initial single microscopically positive node. The patient did not
      receive adjuvant treatment. Evidence regarding the safety of this approach is
      discussed. CONCLUSION: The subject remains controversial, and further such cases
      should be recorded in the literature in order to gather more information on this
      difficult problem.

PMID- 12798725
TI  - A case of chronic paclitaxel administration in ovarian cancer.
AB  - BACKGROUND: Treatment with chemotherapeutic agents, after initial ovarian tumor
      debulking, and during recurrence, results in extended chemotherapy. When ovarian
      cancer recurs, chemotherapy is continued when patients respond to therapy.
      However, the disease may become stable. Stable disease is clinically relevant and
      no longer an indication of treatment failure. CASE: A woman with advanced ovarian
      cancer was treated with cytoxan and cisplatin chemotherapy after having surgical
      cytoreduction. She progressed and was placed on monthly intravenous paclitaxel.
      After an initial partial response to therapy, she then went into a prolonged
      stable course of her disease. She subsequently received 67 cycles of monthly
      paclitaxel therapy. CONCLUSION: Chronic administration of paclitaxel resulted in
      prolonged stabilization of disease and was well tolerated.

PMID- 12798726
TI  - Epithelioid sarcoma of the uterine cervix.
AB  - BACKGROUND: Epithelioid sarcoma is a rare, yet aggressive soft tissue neoplasm
      that has not previously been reported to originate in the cervix. CASE: A 29-year
      old woman was seen in consultation at our institution after having been diagnosed
      with a poorly differentiated carcinoma of the cervix, which was treated with
      radiation and chemotherapy. Examination of the original biopsy material with
      additional studies led to a diagnosis of epithelioid sarcoma of the cervix.
      CONCLUSION: Epithelioid sarcoma can occur in the cervix and should be included in
      the differential diagnosis of cervical neoplasms. Additional cases are needed to
      develop optimum treatment strategies and predict prognosis.

PMID- 12798727
TI  - A pure nongestational choriocarcinoma of the ovary diagnosed with DNA
      polymorphism analysis.
AB  - BACKGROUND: Choriocarcinoma arises in the ovary from gestational or
      nongestational origin. Nongestational choriocarcinoma of the ovary is extremely
      rare and the pure type is less frequent than the mixed type with other germ cell
      tumors. Diagnosis of pure nongestational choriocarcinoma is very difficult
      without genetic analysis. CASE: We report a pure nongestational choriocarcinoma
      primarily arising in a 19-year-old woman's ovary. Following abdominal operative
      procedure, careful examination of the tumor revealed pure choriocarcinoma without
      combination of other germ cell tumors. We confirmed its nongestational origin by
      DNA polymorphism analysis. Multiple courses of chemotherapy with an EMA/CO
      regimen were effective for this case. CONCLUSION: Genetic analysis is useful tool
      in determining the origin of choriocarcinoma. We could distinguish the genetic
      origin of this tumor analyzing only two or three appropriate VNTR loci.

PMID- 12798728
TI  - Malignant struma ovarii: a case report and analysis of cases reported in the
      literature with focus on survival and I131 therapy.
AB  - BACKGROUND: Malignant struma ovarii is a rare type of germ cell tumor that is
      most often diagnosed postoperatively. The natural history and optimal treatment
      regimen for the disease are essentially unknown due to the small numbers of
      published cases. CASE: A 32-year-old woman presented with pelvic pain and an
      ovarian mass that was ultimately treated by total abdominal
      hysterectomy/bilateral salpingo-oophorectomy. Postoperatively, she was diagnosed
      with a malignant struma ovarii. The patient was subsequently treated with
      thyroidectomy and I(131) ablation and is currently disease free. A Medline
      literature search was performed and clinical data from 23 additional cases were
      compiled. CONCLUSION: In this review of 24 cases, 16 patients were followed
      conservatively postoperatively while 8 received varied additional therapy (4 with
      I(131)). There were 8 recurrences and all occurred in the conservatively managed
      patients. I(131) for recurrent disease provided an initial complete response in 7
      women. Treatment with thyroidectomy and I(131) should be considered in the first
      line of management for malignant struma ovarii.

PMID- 12798729
TI  - Vaginal evisceration after hysterectomy: the repair by a laparoscopic and vaginal
      approach with a omental flap.
AB  - BACKGROUND: Vaginal evisceration is generally repaired by vaginal or abdominal
      route. We describe two cases of vaginal evisceration using a combined
      laparoscopic and vaginal approach employing an omental flap. CASES: Case 1: A
      radical abdominal hysterectomy was performed in a premenopausal patient for a
      FIGO IB1 cervical cancer. Four months later, she was found to have a vaginal cuff
      dehiscence which was repaired by a vaginal approach. Two months later, she had a
      vaginal cuff evisceration which was repaired using a combined laparoscopic and
      vaginal approach employing an omental flap with good success. Case 2: A
      postmenopausal woman who underwent an abdominal hysterectomy and pelvic
      lymphadenectomy for a FIGO IB endometrial cancer was noted to have a vaginal
      evisceration two months after primary surgery. This was also successfully
      repaired using a combined laparoscopic and vaginal approach employing an omental
      flap. CONCLUSION: The combined laparoscopic and vaginal approach with omental
      flap is effective for repair of a vaginal cuff dehiscence with bowel
      evisceration. The addition of laparoscopy provides an opportunity for inspection
      of the small bowel, the peritoneal toilet, and mobilization of an omental flap.

PMID- 12798730
TI  - Fractal tumor growth of ovarian cancer: sonographic evaluation.

PMID- 12798743
TI  - The role of tissue factor in colorectal cancer.
AB  - The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A
      correlation between TF expression and advanced stages of malignancy, and a
      correlation between TF expression and overall survival have been suggested in
      CRC. This is supported by experimental studies indicating that TF plays a key
      role in growth, invasion and dissemination of tumour cells, and in tumour related
      angiogenesis as well. In addition, the activation of TF in CRC patients in
      relation to the surgical trauma, perioperative blood transfusion and development
      of postoperative bacterial infectious complications are discussed. Finally,
      future directions for the development of anticancer modalities directed against
      regulation of TF are considered.

PMID- 12798744
TI  - The evolving role of sentinel lymph node biopsy for breast cancer.
AB  - Recent studies have demonstrated that the sentinal node biopsy (SNB), which
      utilizes a simple principle, is a reliable and minimally invasive method for
      determining the status of the regional lymph nodes in patients with clinically
      node-negative breast cancer. The technique has been widely used in the management
      of patients with early breast cancer despite the lack of long-term data from
      randomised controlled trials which are currently in progress. The present article
      reviews the role of the SNB in the context of axillary node sampling and
      determines the requirements for its safe clinical application. It also highlights
      the need for further research to clarify the role of the SNB in high risk DCIS,
      the value of preoperative lymphascintigraphy, and the clinical relevance of
      internal mammary node dissection and focused examination of the sentinal node by
      immunohistochemistry and polymerase chain reaction.

PMID- 12798745
TI  - Learning curve for the detection of axillary sentinel lymph node in breast
      cancer.
AB  - AIM: Sentinel axillary lymph node (SALN) detection is a new technique. Surgeons
      must progress up a learning curve in order to guarantee quality and safety
      equivalent to axillary lymphadenectomy. To ensure accurate staging of patients
      this learning curve must include SALN detection and an axillary lymphadenectomy.
      The aim of our work was to validate the principles and evaluate the consequences
      of learning curve for SALN detection from a prospective series of 200 consecutive
      patients. METHOD: Prospective assessment was made of the detection and false
      negative rates, post operative morbidity as abcess and seroma, and length of
      hospital stay. RESULTS: We evaluated the performance from the first to the
      hundredth case for each surgeon. Detection rate improved to 85% after patient
      number 10. False negative rate was less than 6%. Post operative axillary
      morbidity included 11% of seromas and 2% of abcess. Mean hospital stay was 2.8
      days. CONCLUSION: Multidisciplinary validation of the learning period contributes
      to an accurate and safe SALN.

PMID- 12798746
TI  - What is the impact of breast augmentation on the Breast Screening Programme?
AB  - AIMS: To identify the number of women with breast implants in the Newcastle
      Breast Screening Programme, it's additional workload and compare the number of
      screen detected cancers in the implant and non-implant group. METHODS:
      Retrospective 9 year review of all women with cosmetic breast augmentation who
      have joined the National Breast Screening Programme in Newcastle. RESULTS: The
      percentage of total screened attendances involving implants has increased from 61
      (0.10%) in 1990-93 to 97 (0.14%) in 1993-96 and 135 (0.23%) in 1996-99. Despite
      this increasing workload, no additional resources have yet been required in the
      Breast Screening Unit.1209 cancers (0.57%) were found in the screened population,
      and there were no screen detected cancers in the implant group, and there was no
      significant difference between the groups. CONCLUSIONS: As the number of younger
      women receiving breast implants continues to rise, when they become eligible for
      the National Health Service Breast Screening Programme (NHSBSP), departments
      should be aware that additional personnel and finance will be needed.

PMID- 12798747
TI  - Testicular tumours presenting as gynaecomastia.
AB  - AIM: Gynaecomastia is the commonest benign breast condition seen in men. It is
      usually due to age, co-existing disease, drugs or idiopathic factors. Rarely is
      the cause a testicular tumour. We have assessed those men who were subsequently
      diagnosed as having a testicular tumour in a population of men referred to a
      specialist breast surgeon. METHODS: A retrospective review of 175 men who had
      presented with breast enlargement and/or 'lumps' over seven years (1993-2000) to
      a specialist breast surgeon was performed. All patients were investigated by a
      protocol including biochemical assessment. RESULTS: 175 men, median age 44 years
      (range 18-89) who presented to the breast clinic were assessed. 127 men had
      gynaecomastia (39 bilateral), 8 had breast cancer and 4 had testicular cancer. Of
      the men with testicular tumours, two had bilateral gynaecomastia; a testicular
      mass was palpable in two and the diagnosis confirmed on scrotal ultrasound in all
      four. CONCLUSION: The possibility of a testicular tumour must be considered in
      any male presenting with gynaecomastia. Clinical testicular examination is
      essential and the determination of serum tumour markers useful in the overall
      assessment of those presenting with 'true gynaecomastia'.

PMID- 12798748
TI  - Delay in diagnosis of soft tissue sarcomas.
AB  - AIM: We reviewed 100 patients referred with soft tissue sarcoma between May 1999
      to determine doctor- and patient-related delay. METHODS: Patient delay is defined
      as longer than one month from first symptoms till doctor's visit, doctor delay as
      longer than one month from first visit till definitive diagnosis. Sixty-eight
      patients had a multifactional delay. RESULTS: Forty-seven patients showed patient
      delay, with a median patient delay of 4 months, ranging from 2 to 240 months. The
      main reason for this delay is a painless mass that is mostly ignored. When pain
      is present, median patient delay is shorter.Twenty-seven patients experienced
      doctor delay, ranging from 2 to 79 months, with a median of 6 months. The most
      frequent reason was a misdiagnosis from the outset, on a clinical basis only, or
      due to a wrong diagnosis on ultrasound. Only two of these 27 patients had a
      biopsy, showing a benign tumour. High grade tumours are diagnosed earlier, 85%
      within 6 months. CONCLUSIONS: Delay in diagnosis of soft tissue sarcomas is still
      a problem requiring better patient and doctor education.

PMID- 12798749
TI  - Diffuse sclerosing variant of papillary thyroid carcinoma--clinical features and
      outcome.
AB  - AIM: Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is rare and
      occurs in young patients. This is a single institute retrospective analysis to
      report the clinical features and outcome of DSPC. METHOD: DSPC constituted 8
      (0.74%) of 1086 papillary thyroid carcinomas (PTC) referred to the department of
      Clinical Oncology, Queen Elizabeth Hospital Hong Kong from 1960 to 2000. RESULTS:
      The mean follow-up was 8 years (range: 1.4 to 15.2 years). Six were females and
      two were males, with age ranging from 11 to 48 years. All were ethnic Chinese.
      Compared with the whole cohort of PTC followed in the same period, these patients
      showed younger age at presentation (mean 27.4 vs 45.3 years), larger tumor size
      (mean 6.9 cm vs 2.4 cm), higher incidence of lymph node metastasis (100% vs
      32.4%), and more frequent presence of serum anti-thyroglobulin autoantibody (75%
      vs 11.3%). The patients were managed as for differentiated thyroid carcinoma
      according to the institute's protocol, including total thyroidectomy followed by
      radioiodine (RAI) treatment. External radiotherapy was given to two patients as
      primary treatment and one patient after regional relapse. One patient had distant
      metastases at presentation and she was successfully treated by surgery followed
      by RAI, remaining in complete remission at 12.1 years. One patient had lymph node
      recurrence after primary total thyroidectomy and RAI treatment and was
      successfully salvaged by surgery and external radiotherapy. At last follow-up,
      all eight patients were alive with no evidence of disease. CONCLUSIONS: Although
      DSPC is associated with some unfavourable features at presentation (such as large
      tumor size, extensive lymph node metastasis), the prognosis appears to be as good
      as classical PTC. After aggressive treatment by radical surgery, RAI ablation
      and/or external radiotherapy, the outcome and survival was excellent.

PMID- 12798750
TI  - Bone marrow micrometastases predict early post-operative recurrence following
      surgical resection of oesophageal and gastric carcinoma.
AB  - AIM: Tumour cells in the bone marrow of patients with gastrointestinal cancer may
      detect patients at higher risk of disease recurrence and death following
      potentially curative surgery. METHODS: Immunocytochemistry using the monoclonal
      antibody Ber-EP4, which detects tumour cells from squamous and adenocarcinomas
      was used. In preliminary spiking experiments to define sensitivity, tumour cells
      were detected in blood at 10(3)/ml. Bone marrow samples from 74 patients with
      oesophago-gastric cancer and from 14 control patients was examined. RESULTS: 27
      (36.5%) patients with cancer and one control patient had stained cells present in
      their bone marrow at the time of resection. During the follow up period (mean 14
      months), relapse and disease-specific death were commoner in patients whose
      marrow contained tumour cells. Multivariate analysis confirmed bone marrow
      micrometastasis as an independent prognostic variable for both recurrence and
      survival. CONCLUSIONS: Bone marrow immunocytochemistry using Ber-EP4 may identify
      those patients at highest risk of early relapse following RO resection of
      oesophageal or gastric cancer.

PMID- 12798751
TI  - Radical prostatectomy for locally advanced primary or recurrent rectal cancer.
AB  - AIM: Three papers including five patients have described en bloc radical
      prostatectomy for locally advanced rectal cancer. METHODS: Six patients (median
      age 63 years) underwent en bloc radical prostatectomy for locally advanced (3) or
      recurrent (3) rectal cancer involving the prostate. Quality of life
      questionnaires were answered postoperatively and the data prospectively entered
      in a database. RESULTS: One primary case had low anterior resection (LAR), the
      others abdominoperineal resections (APR) of R0 stage. Two recurrent cases had
      APRs and one tumour resection-all R1 stage. Anastomotic leakage led to
      construction of an ileal conduit in one patient and in two healed on conservative
      treatment. Follow up was 10-50 months. One patient died from distant metastases
      at 29 months postoperatively, one was operated for a single lung metastasis and
      one has disseminated lung metastases. None has developed local recurrence. Four
      of the five with anastomoses had good quality of life and none wanted an ileal
      conduit. CONCLUSION: In spite of a relatively high urinary leak rate the total
      complication rate seems to be lower than after pelvic exenteration. En bloc
      radical prostatectomy seems an option in selected patients otherwise needing
      pelvic exenteration for locally advanced or recurrent rectal cancer.

PMID- 12798752
TI  - A comparison between hepatic artery ligation and portal 5-Fu infusion versus 5-Fu
      intra arterial infusion for colorectal liver metastases.
AB  - AIM: A prospective randomized study was executed comparing two regimens of
      regional therapy for liver metastases from colorectal cancer. METHODS: Eighteen
      patients were allocated to hepatic artery occlusion for 16 h followed by
      intraportal 5-fluorouracil (5-Fu) infusion (1000 mg/m(2)) for 5 days every sixth
      week (HAO). Twenty-one patients received intra-arterial 5-Fu infusion+Leucovorin
      (100 mg) i.v. for 2 days every second week (HAI). The follow up every third month
      included CT and CEA. Thirteen patients had limited extrahepatic cancer. At tumor
      progression regional therapy was stopped and systemic chemotherapy or the best
      supportive care was administered. RESULTS: The study was discontinued after
      randomization of 39 patients. No significant difference in survival within
      patients with and without extrahepatic cancer was present. The mean survival was
      longer in the HAI group than for the HAO group (19 months versus 13 months,
      p=0.0147) (median 18 (8-37) versus 12 (2-26). PR and SD were registered in 8/18
      in the HAO group and 17/21 patients in HAI group. The median time to progress was
      4 (1-22) months versus 7 (1-23) months for the HAO and HAI group, respectively.
      CONCLUSION: Regional intraarterial infusion with 5-Fu gives significantly better
      survival than hepatic artery occlusion followed by portal infusion. A limited
      amount of extrahepatic cancer does not influence survival time. A trial comparing
      hepatic artery 5-FU infusion and Leucovorin versus the most effective systemic
      therapy is warranted.

PMID- 12798753
TI  - Review of surgical management of aldosterone secreting tumours of the adrenal
      cortex.
AB  - AIMS: To evaluate the investigation and surgical management of primary
      hyperaldosteronism. Retrospective case note analysis of thirty-three patients who
      underwent adrenalectomy for primary hyperaldosteronism between 1982 and 2001 and
      a current relevant literature review. METHODS: The records of twelve male and
      twenty-one female patients, age range 18 to 81 (mean 48 years) were reviewed.
      Eleven operations were performed by an open approach and twenty-two
      laparoscopically. Preoperative investigations included computed tomography (CT),
      magnetic resonance imaging (MRI), selective venous sampling and seleno
      cholesterol isotope scanning, along with biochemical and hormonal assays. Twenty
      six benign adenomas, three nodular hyperplastic lesions, one primary adrenal
      hyperplasia and three functional carcinomas were excised. Mean follow up was 12
      months. RESULTS: Patients had a mean blood pressure of 185/107 mmHg for 6.2 years
      mean duration. The mean severity of hypokalaemia was 2.7 mmol/l. Sensitivity of
      CT scanning was 85%, and of MRI 86%. Fifty percent of seleno-cholesterol scans
      were accurate. Mean operating time was 158 min for laparoscopic adrenalectomy
      whilst open surgery took 129 min (p=0.2, NS). Two cases commenced
      laparoscopically required open access for control of primary haemorrhage whilst
      one other bleed was managed via the operating ports. Mean postoperative stay was
      significantly shorter for the laparoscopic group (3 days compared with 7.9 days,
      p<0.0001). Thirty day mortality was zero. There were three infective
      complications in the open group (two chest, one wound) with no postoperative
      complications in the laparoscopic group. All patients were cured of hypokalaemia,
      whilst 62% cure of hypertension was achieved. Of those patients whose blood
      pressure was improved preoperatively by spironolactone 78% were cured by
      adrenalectomy. Adrenalectomy led to an overall reduction in the mean number of
      anti-hypertensive medications (2.3 drugs preoperative to 0.6 postoperative,
      p<0.0001). Of those not cured, 58% had improved blood pressure control requiring
      less medication on average (1.6 drugs compared with 2.6 drugs, p=0.08). Mean age
      of patients not cured by surgery was 55 years, whilst those cured was 44 years
      (p=0.03). CONCLUSIONS: Primary hyperaldosteronism is a rare but important cause
      of hypertension. Selective venous sampling is a useful tool where investigations
      are inconclusive and fail to lateralise secretion. Patients with primary
      hyperaldosteronism enjoy lower complication rates and earlier discharge with the
      advent of laparoscopic surgery. Most patients will be cured of their hypertension
      and all of hypokalaemia. Laparoscopic adrenalectomy is now the accepted method of
      surgery for benign hyperaldosteronism. Those with bilateral disease due to
      idiopathic hyperaldosteronism (IHA) are not candidates for surgery and should be
      treated medically.

PMID- 12798754
TI  - Breast cancer risk among the survivors of atomic bomb and patients exposed to
      therapeutic ionising radiation.
AB  - Radiation induced breast cancer is a highly complex phenomenon, which most likely
      involves the accumulation of several genetic and epigenetic events. Studies of
      atomic bomb survivors, patients who underwent multiple fluoroscopic examinations
      during treatment for pulmonary tuberculosis, those who received therapeutic
      radiation for benign breast disease, such as acute post-partum mastitis, or those
      with an enlarged thymus or skin haemangioma and patients with Hodgkin's disease
      treated by mantle radiotherapy established that the risk of breast cancer
      increases with exposure to ionising radiation. The carcinogenic effect of
      therapeutic or accidental radiation is highest when exposure occurs during
      childhood and exposure after age 40 imparts low or minimal risk. The risk of
      bilateral breast cancer is not significantly increased in the survivors of atomic
      bomb and therapeutic radiations. Fractionated exposures for therapeutic radiation
      are similar to a single exposure of the same total dose in their ability to
      induce breast cancer; this risk remains high for many years after exposure.
      Younger age at first full term pregnancy confers a protective effect against the
      risk of breast cancer in the survivors of atomic bomb but long-term data on this
      beneficial effect after therapeutic radiation is not available.

PMID- 12798755
TI  - Response to correspondence from Kauimarz Sethna, Faheez Mohamed and Paul H.
      Sugarbaker, EJSO 2002; 28 (8): 897.

PMID- 12798756
TI  - Radiofrequency ablation management of liver tumours, Gillams AR (EJSO 2003, 29
      pages 9-16).

PMID- 12798758
TI  - Assessment of essential and toxic elements in some kinds of vegetables.
AB  - Vegetables provide the human body with the essential bioavailable trace elements,
      and a constant supply of these various elements is necessary and highly
      recommended for daily life. Minor elements such as Ca, Fe, K, Mg, and Na as well
      as trace elements such as Cd, Co, Cu, Mn, Ni, Pb, and Zn were determined using an
      atomic absorption spectrophotometer in 12 different species of vegetables from
      Saudi Arabia (the Al-Taif district). These vegetables were cucumber, vegetable
      marrow, tomato, potato, green pepper, eggplant, carrots, parsley, lettuce,
      spinach, salq, onion, leek, watercress, and cabbage. The results reveal that the
      different element concentrations of each vegetable depend upon the selective
      uptake of the elements by the plant. Salq and watercress exhibited higher element
      concentrations than the other vegetables. Cluster analysis, principle component
      analysis, and transfer factor analysis of elements from soil to plant were
      applied to the elements database and produced good interpretations of the data.
      The element concentrations of these vegetables were within safety baseline levels
      for human consumption.

PMID- 12798759
TI  - The use of respiratory enzymes as biomarkers of petroleum hydrocarbon exposure in
      Mytilus edulis planulatus.
AB  - The effect of exposure to petroleum hydrocarbons via the water column and through
      contaminated sediment upon changes in respiratory enzymes in the common mussel
      (Mytilus edulis planulatus) was investigated. Mussels were exposed to three
      concentrations of the water-accommodated fraction (WAF) of Bass Strait crude oil,
      for 24, 48, and 96 h. In a second study mussels were exposed to three
      concentrations of crude oil-contaminated sediment for 2 weeks and 1, 2, 4 and 6
      months. Activities of citrate synthase (CS) and lactate dehydrogenase (LDH) were
      measured in the gills. In mussels exposed to WAF, a significant decrease in CS
      activity was observed over time (P<0.05), whereas treatment did not cause a
      significant change in CS activity (P>0.05); neither treatment nor time had an
      effect on LDH activity. Exposure to contaminated sediment did not have a
      significant effect on CS activity, however, time had a significant effect on CS
      activity (P<0.05). Both time and treatment had an effect on LDH activity
      (P<0.05). Results demonstrated that changes in gill CS and LDH are not sensitive
      biomarkers of petroleum hydrocarbon exposure in M. edulis planulatus.

PMID- 12798760
TI  - Pigments as biomarkers of exposure to the vineyard herbicide flazasulfuron in
      freshwater algae.
AB  - Weed control in Champagne vineyards has long relied on the use of diuron and
      substituted triazines; these compounds are now being replaced by flazasulfuron, a
      sulfonylurea that is used at a much lower dosage. The vineyards of Champagne are
      planted on steep slopes and runoff is important, and even though low doses of
      these herbicides are used, they may present some potential risk for freshwater
      ecosystems. Therefore, the effects of the sulfonylurea herbicide, flazasulfuron
      (formulated as Katana) was investigated on the unicellular green alga Scenedesmus
      obliquus. The pigment content of the algal suspensions was followed as a
      biomarker of exposure to the herbicide. The results demonstrate that
      flazasulfuron induced a reduction in chlorophyll content at concentrations of 10
      microg/L, while the increase of pigment content in the culture was reduced with
      the lowest concentration tested (0.1 microg/L). Among the three pigments tested,
      chlorophyll a appeared to be the most sensitive biomarker. In the algal medium,
      flazasulfuron was slowly degraded (DT(50) approximately 8 days) in a compound
      that was tentatively identified. The toxicity of this herbicide for the algae was
      comparable to that of older herbicides which are used at a much higher rate.
      Therefore, we may speculate that even if flazasulfuron comes into contact with
      freshwater ecosystems, its effects on algae will be less deleterious than that of
      traditional herbicides.

PMID- 12798761
TI  - Bioaccumulation and toxicity of fluoranthene in the estuarine oligochaete
      Monopylephorus rubroniveus.
AB  - The tolerance of the estuarine oligochaete Monopylephorus rubroniveus to
      fluoranthene was characterized both in the presence and absence of ultraviolet
      (UV) radiation. Using waterborne exposures, the 72-h median lethal concentration
      (LC(50)) and median lethal dose (LD(50)) were 0.7 (95% CI, 0.4-0.8) microg/L and
      8.0 (5.6-9.6) microg/g worm dry weight, respectively, in the presence of UV
      radiation [UV-A=64.7+/-1.0 mu W/cm(2) (mean+/-standard deviation)]. In the
      absence of UV radiation, little mortality was observed, even at the water
      solubility limits of fluoranthene (120.4 microg/L). Mean bioconcentration factors
      across all treatments was 10,893+/-2828. Using sediment exposures, little
      mortality was observed following 10 days at concentrations as high as 3912 microg
      fluoranthene/g sediment dry weight in both the presence of UV radiation (UV
      A=108.4+/-1.3 mu W/cm(2)) and its absence. Bioaccumulation of sediment-associated
      fluoranthene was comparatively high and varied little among the five sediment
      treatments. The results of the present study demonstrate that M. rubroniveus is
      (1) sensitive to waterborne fluoranthene in the presence of UV radiation and (2)
      highly tolerant of fluoranthene in the presence of sediment, despite the ability
      to bioaccumulate fluoranthene to comparatively high levels. These findings
      suggest that those environmental factors which could potentially increase their
      exposure to UV radiation need to be considered when assessing the overall risk of
      fluoranthene to M. rubroniveus.

PMID- 12798762
TI  - Absence of cadmium excretion and high assimilation result in cadmium
      biomagnification in a wolf spider.
AB  - Cd biomagnification in the terrestrial food chain appears to be dependent on the
      physiological properties of the organisms rather than on their trophic level.
      Although high Cd body burdens in spiders from the field have been reported many
      times, experimental verification of the key factors that determine the rate of
      cadmium accumulation is lacking. We investigated the cadmium assimilation rate in
      the common wolf spider Pirata piraticus fed with contaminated fruit flies.
      Spiders were fed for 42 days with contaminated flies, followed by a
      detoxicification period of 28 days. Every 14 days, a subsample of spiders and
      flies was taken for Cd determination. It was demonstrated that a high cadmium
      assimilation (69.5%) and an excretion rate approaching zero resulted in high Cd
      concentration factors. The results indicate the importance of spiders in cadmium
      biomagnification along critical pathways.

PMID- 12798763
TI  - Blood and hair lead levels in boys and girls living in two Sardinian towns at
      different risks of lead pollution.
AB  - This study reports blood and hair lead levels measured in 1998 in 222 children
      from two Sardinian towns: Portoscuso and Sestu. Portoscuso is in a polluted area
      of Sardinia due to its vicinity to the industrial zone of Portovesme. As a
      consequence of its economy and location, Sestu is not exposed to lead pollution.
      Blood lead (PbB) concentration was determined in heparinized venous blood samples
      by graphite furnace atomic absorption spectrophotometry (AAS). Hair lead (PbH)
      concentration was determined by inductively coupled plasma atomic emission
      spectrometry (ICP-AES). With respect to blood lead levels, the boys of Portoscuso
      have the highest arithmetic mean value (11.30 microg/dL), followed by the
      Portoscuso girls (7.39 microg/dL); they are followed, but with much lower values,
      by the boys (4.09 microg/dL) and girls (3.34 microg/dL) of Setsu. For hair lead
      levels, the Portoscuso boys have the highest arithmetic mean value (15.51
      microg/g), followed by the Portoscuso girls (8.82 microg/g) and the Sestu boys
      (4.03 microg/g) and girls (2.83 microg/g). Therefore the mean values of PbB and
      PbH follow similar patterns in the boys and girls of the two Sardinian towns. Two
      way ANOVA reveals a significant effect of sex and town on log PbB and log PbH.
      Moreover, values of the Bravais-Pearson coefficients of correlation between log
      PbB and log PbH are statistically significant for the total sample (r=0.5086;
      P<0.001), for males (r=0.4275; P<0.01), and for females (r=0.4859, P<0.001). The
      sensitivity of the hair lead analysis in identifying lead concentrations above 10
      microg/g is 49%. The results support the hypothesis that hair lead levels can be
      considered an indicator of different relative exposure of populations to lead
      pollution.

PMID- 12798764
TI  - Dicentrarchus labrax biotransformation and genotoxicity responses after exposure
      to a secondary treated industrial/urban effluent.
AB  - The present research work was designed to study Dicentrarchus labrax (sea bass)
      biotransformation and genotoxicity responses to the soluble fraction of a
      secondary treated industrial/urban effluent (SF-STIUE) discharged through a
      submarine pipe outlet into the Aveiro coastal area. Sea bass was exposed for 4,
      8, 16, 24, 48, and 96 h to 0%, 0.1%, and 1% SF-STIUE and the following biological
      responses were measured: (1) liver cytochrome P450 (P450) content and
      ethoxyresorufin-O-deethylase (EROD) activity, as phase I biotransformation
      parameters; (2) liver gluthathione S-transferase (GST) activity as a phase II
      conjugation enzyme; (3) biliary and liver cytosol naphthalene (Naph)- and
      benzo(a)pyrene (B(a)P)-type metabolites, by fixed wavelength fluorescence
      detection (FF); (4) liver DNA strand breaks, erythrocytic micronuclei (EMN), and
      erythrocytic nuclear abnormalities (ENA) as genotoxicity parameters. Both SF
      STIUE dilutions (0.1% and 1%) failed to significantly increase liver EROD
      activity, despite a significant increase of liver P450 at 16 and 48 h exposure to
      0.1%. Liver GST activity increased significantly at 4h of sea bass exposure to 1%
      SF-STIUE, being inhibited at 96 h of exposure to this SF-STIUE dilution. Naph-
      and B(a)P-type metabolite contents were not significantly increased in bile.
      However, Naph-type metabolite contents increased significantly in liver cytosol
      at 4h exposure to 1% SF-STIUE, and at 24h exposure to 0.1% and 1% SF-STIUE.
      Furthermore, B(a)P-type metabolites increased significantly in liver cytosol at
      4h exposure to 1% SF-STIUE, and 16 h exposure to 0.1% and 1% SF-STIUE. EMN and
      ENA frequencies increased significantly at 4, 8, 16, 24, 48, and 96 h exposure to
      0.1% and 1% SF-STIUE. Liver DNA integrity decreased significantly at 96 h of sea
      bass exposure to 1% SF-STIUE. The STIUE discharged into Aveiro coastal area is of
      great ecotoxicological concern due to its genotoxic potential.

PMID- 12798765
TI  - Assessment of antifertility activities of abamectin pesticide in male rats.
AB  - The effects of abamectin pesticide on fertility of adult male Sprague-Dawley rats
      were investigated. Adult male rats were exposed to tap water containing 0, 571,
      857, or 1714 ppm abamectin for 6 weeks. Based on fluid consumption, animals
      received 0, 1.19, 1.87, and 2.13 mg/animal/day abamectin, respectively. Fertility
      was significantly reduced in male rats ingesting abamectin at all three doses in
      that the number of females impregnated by them was significantly reduced. The
      number of viable fetuses was significantly reduced in females mated with males
      that ingested abamectin at 1.87 or 2.13 mg/animal/day. Significant increases in
      the total number of resorptions and the number of females with resorptions were
      observed in females mated with the exposed males at all three concentrations. The
      body weight gain and water consumption were significantly lower in males that
      ingested 2.13 mg/animal/day abamectin. Likewise, ingestion of abamectin at all
      three concentrations caused a significant increase in the weight of testes.
      Epididymal and testicular sperm counts and daily sperm production were
      significantly decreased in exposed males. The serum level of testosterone was
      significantly reduced, whereas the serum level of follicle-stimulating hormone
      was significantly increased in males that ingested abamectin at a concentration
      of 2.13 mg/animal/day. Histological evaluation of the testes revealed several
      abnormalities including infiltration with congested blood vessels with marked
      hemorrhage and a significant accumulation of connective tissue surrounding the
      seminiferous tubules. These results strongly suggest the adverse effects of
      abamectin pesticide on male rat fertility.

PMID- 12798766
TI  - Fertilization and embryonic development of whitefish (Coregonus lavaretus
      lavaretus) in acidic low-ionic-strength water with aluminum.
AB  - The fertilization rate and extent of the cortical reaction of anadromous
      whitefish decreased with increasing acidity (0.034 mmol Ca(2+)L(-1)); at pH 4.5
      the fertilization rate was 46% of that at pH 6.5. Aluminum (250 microg L(-1))
      decreased the percentage fertilization independently of pH and reduced the
      cortical reaction magnitude at all pH levels. In eggs at pH 5.0, especially at pH
      4.5, and in solutions with Al, the growth of embryos was impaired by a
      perivitelline space that was too narrow. The proportion of embryos with a curved
      tail tip and those with blood circulation failure increased with decreasing pH.
      No fry hatched at pH 4.5 and those few that hatched at pH 5.0 did not survive. No
      fry survived Al-containing water at pH 5.5 and survival was decreased at pH 6.5
      with Al. It is concluded that for successful recruitment of anadromous whitefish,
      pH should preferably remain >5.5 in dilute soft water when toxic concentrations
      of Al are present.

PMID- 12798767
TI  - The effects of 4-nonylphenol and ethanol on acute toxicity, embryo development,
      and reproduction in Daphnia magna.
AB  - The mean 48-h EC(50) (n=3) of 4-nonylphenol (NP) using ethanol as the carrier
      solvent was 155 microg/L, compared to a mean 48-h EC(50) (n=3) of 281 microg/L
      without ethanol. The 96-h EC(50)'s for embryo lethality (arrested egg
      development) and deformities (curved or unextended shell spines and undeveloped
      second antennae) were 738 and 263 microg/L, respectively. Reproduction studies
      were conducted using conditions that stimulate male production (i.e., reduced
      photoperiod and food levels). An increase in neonate deformities was observed at
      50 microg/L (without ethanol), but no changes were observed in fecundity or sex
      ratios. A decrease in sex ratios was observed at 25 and 50 microg/L (with
      ethanol) compared to the ethanol control. However, an increase in sex ratios was
      observed in the ethanol control compared to media controls. The use of ethanol as
      a solvent carrier confounds the effects of 4-NP on acute toxicity and male
      production in daphnids.

PMID- 12798768
TI  - Sister chromatid exchange induction by the herbicide 2,4-dichlorophenoxyacetic
      acid in chick embryos.
AB  - As genetic damage may result from exposure to agricultural chemicals, it seemed
      appropriate to assess the genotoxic potential of 2,4-dichlorophenoxyacetic acid
      (2,4-D), a widely used broad-leaf herbicide, using a test system that may provide
      some indications on the genetic risk to animal species in the wild. In the
      present study, sister chromatid exchange (SCE) induction and cell cycle kinetics
      alterations by 2,4-D in 4-day old chick embryos were evaluated. Both a commercial
      herbicide formulation containing 37% 2,4-D isooctyl ester as active ingredient
      and pure 2,4-D were tested. Chick embryos were treated with 0, 0.5, 1, 2, or 4 mg
      2,4-D. Test solutions were applied to the inner shell membrane on day 0 of
      incubation. Either commercial formulation or pure 2,4-D induced a dose-related
      increase in SCE frequency over the concentration range from 0 to 4 mg/embryo.
      Significantly higher SCE frequency was seen for the 4-mg group of embryos treated
      with the commercial product. A slightly higher SCE value was observed for the
      vehicle group (acetone-treated embryos) compared with the negative controls
      (untreated embryos). Significant inhibition of cell cycle progression was evident
      in both experimental groups and was generally dose related. The extent of changes
      in cell kinetics was similar in both groups, although somewhat more marked in the
      group treated with pure 2,4-D. The present findings corroborate the positive
      results from recent in vivo rodent studies.

PMID- 12798769
TI  - Changes in microbial properties associated with long-term arsenic and DDT
      contaminated soils at disused cattle dip sites.
AB  - This work examined the effect of long-term arsenic (As) and DDT contamination on
      soil microbial properties at 11 cattle dip sites in northern New South Wales,
      Australia. Total As in the surface (0-10 cm) soils from these sites ranged from
      34 to 2941 mg As kg(-1) soil and hexane-extractable DDT concentrations ranged
      between 2.9 and 7673 mg DDT kg(-1) soil. The concentrations of water and oxalate
      extractable As were positively correlated with total As. Oxalate-extractable As
      was more strongly correlated (r(2)=0.87) with total As than water-extractable As
      (r(2)=0.34). A weak positive relationship was observed between the level of
      nutrient (organic carbon and nitrogen) and microbial biomass C (r(2)=0.61 and
      0.45, respectively). There was a highly significant difference between the
      microbial properties of polluted and unpolluted sites (P<0.001). In comparison to
      unpolluted soils, fungal counts, microbial biomass C, and respiration were
      dramatically reduced (P<0.05) in polluted soils. However, the bacterial
      population between polluted and unpolluted soils were not different (P<0.05). The
      results of this study suggested that (a) long-term contamination of soils
      adjacent to former cattle dipping sites by As and DDT adversely affected soil
      microbial properties with the fungal populations being the most sensitive and (b)
      there was little regeneration of microbiota despite 25 years of field ageing of
      the soils.

PMID- 12798770
TI  - Genotoxicity biomarkers' association with B(a)P biotransformation in
      Dicentrarchus labrax L.
AB  - Dicentrarchus labrax (sea bass) were exposed during 0, 4, 8, 16, 24, 48, and 96 h
      to 0 and 0.1 microM benzo(a)pyrene (B(a)P), an environmental pollutant, and the
      following biomarkers were measured: (1) liver cytochrome P450 (P450) content and
      ethoxyresorufin-O-deethylase (EROD) activity as phase I biotransformation
      parameters, (2) liver gluthathione-S-transferase (GST) activity as a phase II
      biotransformation conjugation enzyme, (3) biliary and liver cytosolic B(a)P-type
      metabolites by fixed wavelength fluorescence detection (FF), and (4) erythrocytic
      micronuclei (EMN) and erythrocytic nuclear abnormalities (ENA) as genotoxicity
      biomarkers. Liver EROD activity (4 h), P450 content (24 h), GST activity (4, 8,
      and 96 h), bile (4-96 h), and liver cytosolic (4-24 h) B(a)P-type metabolites
      increased significantly in sea bass exposed to B(a)P as well as EMN (8-96 h) and
      ENA (4-96 h) frequencies. B(a)P genotoxicity is associated with increase in B(a)P
      type metabolites in liver cytosol due to an impaired phase II conjugation. This
      increase seems to be responsible for the decrease in liver EROD and GST
      activities.

PMID- 12798771
TI  - Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of
      carbamazepine, clofibric acid, and diclofenac.
AB  - In four countries (France, Greece, Italy, and Sweden) occurrence in sewage
      treatment plant (STP) effluents and ecotoxicity of the pharmaceuticals
      carbamazepine, clofibric acid, and diclofenac were investigated. Bioassays were
      performed on bacteria, algae, microcrustaceans, and fishes in order to calculate
      their predicted no-effect concentrations (PNEC) and to perform a first approach
      of risk characterization. For this aim, risk has been estimated by the predicted
      environmental concentration/PNEC ratio and the measured environmental
      concentration/PNEC ratio. First, regarding the PNEC, carbamazepine appears to be
      the more hazardous compound. Second, even though it is demonstrated that
      carbamazepine, clofibric acid, and diclofenac have been detected in effluents,
      only carbamazepine have been detected in all sewage treatment plants with the
      greatest concentrations. Third, risk quotients greater than unity were calculated
      only for carbamazepine, suggesting that risk for the water compartment is
      expected.

PMID- 12798772
TI  - Possible origin of a membrane in the subsurface of the Earth.
AB  - A location for the origin of life on Earth could have been an oil/water interface
      in the warm, subsurface environment of the Earth. The physico-chemical conditions
      of the subsurface would include elevated, but eventually cooling temperatures,
      anaerobic conditions, and protection from intense surface radiation. This type of
      subsurface oil/water environment may have been ideal for the assembly of the
      first simple membrane(s), where no enzyme catalysis was needed. Once a stable,
      simple, continuous closed membrane was formed, one central component of the first
      cell(s) would have been present; a semi-permeable open system that allowed the
      passage of both matter and energy in and out of the cell. Such an open system
      could also acquire novel functions, whereas a closed system would be unable to
      evolve.

PMID- 12798773
TI  - The expression of matrix metalloproteinase-13 and osteocalcin in mouse
      osteoblasts is related to osteoblastic differentiation and is modulated by 1,25
      dihydroxyvitamin D3 and thyroid hormones.
AB  - Matrix metalloproteinase-13 (MMP-13), is a key protein of bone matrix
      degradation, and is highly expressed by osteoblasts. We used the osteoblast-like
      MC3T3-E1 cell line and compared the stimulatory effects of the bone resorptive
      agents 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) 3,3',5-triido-L-thyronine (T3)
      on the expression of MMP-13 mRNA. We showed that the stimulatory effects were
      time and dose dependent, and were also transduced to the protein level, with 1,25
      (OH)(2)D(3)being more potent.MMP-13 expression in different mouse cells and its
      localization within developing bone from the onset of osteogenesis were also
      investigated. 1,25-(OH)(2)D(3)- and T3-regulated osteocalcin (Osc) expression in
      mouse osteoblasts was compared to hormonal effects on MMP-13 expression and
      activity. Here we show divergent and common roles of 1,25-(OH)(2)D(3)and T3
      action on the expression of these marker proteins, depending on the stage of cell
      differentiation. In addition, we propose a role for MMP-13 in the bone collar of
      developing long bones. The results could help to more precisely characterize
      hormonal regulation in the developmental sequence of osteoblasts.

PMID- 12798774
TI  - The nifk gene is widely expressed in mouse tissues and is up-regulated in
      denervated hind limb muscle.
AB  - Denervation of skeletal muscle alters the expression of many genes, which may be
      important for establishing optimal conditions for reinnervation. Using the
      differential display technique we have attempted to discover neurally regulated
      genes in skeletal muscle. An mRNA that is up-regulated in denervated hind limb
      muscle was identified and cloned. The cDNA encodes an RNA-binding protein, which
      was discovered during the course of this work to be a nucleolar protein
      interacting with the fork-head associated domain of the proliferation marker
      protein Ki-67, and named NIFK. We show that the nifk gene is widely expressed in
      adult mouse tissues and that the expression is up-regulated in denervated hind
      limb muscle. No difference between expression in perisynaptic and extrasynaptic
      portions of muscle was observed. The widespread expression in adult tissues
      suggests that the NIFK protein has other functions in addition to its interaction
      with Ki-67, which is only expressed in proliferating cells.

PMID- 12798775
TI  - Erb-B2 homodimerization inhibits MUC1 transcription in cultured human mammary
      epithelial cells.
AB  - MUC1 mucin is a heavily O-glycosylated transmembrane protein that is aberrantly
      expressed in many carcinomas, including breast cancer. In the present study, the
      effect of signaling generated from the Erb-B2 homodimer as a result of
      transcription of the MUC1 gene was investigated in human mammary epithelial cell
      lines (MTSV1-7 and Hb2) stably transfected with a pBAT/trk-neu construct in which
      the extracellular domain of Erb-B2 was replaced with the corresponding domain
      from the nerve growth factor (NGF) receptor. In this system, NGF stimulated
      homodimerization of Erb-B2 and phosphorylation of its intracellular domain. MTSV1
      7/trk-neu and Hb2/trk-neu cells were transiently transfected with a construct in
      which the MUC1 promoter caused expression of a CAT reporter gene, and were then
      treated with NGF. These studies showed that MUC1 expression was inhibited by NGF
      treatment in both cell lines, suggesting that its expression can be regulated by
      signals resulting from the homodimerization of Erb-B2.

PMID- 12798776
TI  - Antioxidants prevent UV-induced apoptosis by inhibiting mitochondrial cytochrome
      c release and caspase activation in Spodoptera frugiperda (Sf9) cells.
AB  - Oxidative stress has been shown to be associated with apoptosis (programmed cell
      death) in a number of cell systems. We earlier reported in vitro cultured
      Spodoptera frugiperda (Sf9) cells as a model system to study oxidative stress
      induced apoptosis (J Biosciences 24 (1999) 13) and the inhibition of UV-induced
      apoptosis by the baculovirus antiapoptotic p35 protein that acts as a sink to
      sequester reactive oxygen species (Proc Natl Acad Sci USA 96 (1999) 4838). We now
      show that UV-induced apoptosis in Sf9 cells, is preceded by the release of
      mitochondrial cytochrome c into the cytosol and consequent activation of Sf
      caspase-1. The inhibitory effect of different antioxidants including scavengers
      of oxygen radicals such as butylated hydroxyanisole (BHA), alpha tocopherol
      acetate, benzoate and reduced-glutathione (GSH) on ultra violet B (UVB)-induced
      apoptosis in cultured Sf9 cells was assessed. Both, cytochrome c release as well
      as Sf-caspase-1 activation was inhibited by pre-treatment with antioxidants such
      as BHA and alpha tocopherol acetate, suggesting that these antioxidants inhibit
      apoptosis by acting quite upstream in the apoptosis cascade at the mitochondrial
      level, as well as downstream at the caspase level.

PMID- 12798778
TI  - Redistribution and unmasking of Annexin V binding sites in apoptotic Raji cells.
AB  - The complement receptor type 2 (CR2) associates with other surface antigens and
      proteins and its redistribution and/or unmasking occurs through still unknown
      mechanism(s). The data presented demonstrate that high-density cultured CR2
      positive cells undergo apoptosis and that the redistribution and unmasking of
      Annexin V binding sites occurs in a fashion similar to the redistribution and
      unmasking of CR2. Therefore, apoptotic and non apoptotic cells from the same
      lineage may share a similar mechanism for the exposition of neo-surface markers

PMID- 12798777
TI  - Expression of Tra2beta isoforms is developmentally regulated in a tissue- and
      temporal-specific pattern.
AB  - The contribution of Tra2-regulated alternative splicing to mammalian development
      is unknown. To address the question, we initiated studies by systemically
      characterizing the gene expression profile of Tra2beta isoforms in human fetal
      tissue at two different stages (11 and 16 weeks). Tra2beta has at least five
      isoforms of transcripts (Tra2beta1 approximately 5). Tra2beta1 encodes full
      length Tra2beta proteins, whilst Tra2beta3, 4 and 5 encode the truncated
      proteins. The results show that Tra2beta1 transcript levels are developmentally
      regulated in a tissue- and temporal-specific pattern, although expression is
      ubiquitous. Compared to Tra2beta5, the expression of Tra2beta3 and 4 transcripts
      is significantly restricted and more vigorously regulated in a tissue- and
      temporal-specific pattern. Western blot analysis shows that Tra2beta1 proteins
      are ubiquitously expressed, but at a relatively higher level in neural tissues
      than non-neural tissues. However, there is no direct correlation between the
      transcript and protein levels for Tra2beta1, suggesting that multiple mechanisms
      are involved in the regulation of Tra2beta during development. This study
      indicates that Tra2beta-regulated splicing may contribute to the regulation of
      mammalian development in a tissue- and temporal-specific pattern.

PMID- 12798779
TI  - History of food acceptance research in the US Army.
AB  - The history of food acceptance research by the US Army in Chicago and Natick is
      reviewed. The review covers the staff of the two research centers, the research
      programs, and the significant accomplishments of the Army laboratories from the
      1940s to the present. Accomplishments begin with the development of the nine
      point hedonic scale, and the development of the first Food Acceptance Laboratory.
      Further accomplishments include studies of sensory psychophysics, food
      preferences, food choice and food intake. The laboratories designed methods and
      conducted research on the role of consumer variables in the acceptance of food
      products and food service systems. Recent work has focused on new scaling
      approaches, the role of contextual factors and the importance of product
      expectations. Throughout the period of the review, the Army research has examined
      the relationship of laboratory acceptance to field acceptance, and the
      relationship of acceptance to intake.

PMID- 12798780
TI  - Consumer concerns and expectations about novel food processing technologies:
      effects on product liking.
AB  - Eighty-eight consumers participated in a blind pre-test in which they rated their
      baseline preference for chocolate pudding, their liking of three tasted brands of
      chocolate pudding, and their level of concern for 20 different food processing
      and preservation technologies. All returned one month later and tasted the same
      puddings, but this time they were informed that they had been processed by one of
      several different novel or traditional food processing techniques. Different sub
      groups were informed of the name of the process, the name plus a factual
      description of the process, or the name, the factual description, plus a benefit
      statement. Ratings of expected liking were obtained before and after viewing the
      samples, but before tasting them. Finally, subjects tasted and rated the products
      for actual liking and a sub-group rated their concern levels for the same 20
      technologies rated in the pre-test. Pre-test results showed females to have
      significantly higher concern levels for all technologies. Individuals who had
      demonstrated a willingness to consume foods processed by one novel technology
      (irradiation) had lower concern ratings for all technologies. Ratings of concern
      were negatively correlated with expected liking for products believed to be
      processed by the technologies. Expected liking ratings were positively influenced
      by visual exposure to the product and by a safety and benefit statement. Linear
      regression of the change in product liking as a function of whether products were
      better or worse than expected supported an assimilation model of the effect of
      disconfirmed expectations on liking/disliking. Lastly, post-test concern levels
      for many of the technologies were reduced by participation in the study.

PMID- 12798781
TI  - The construct of food involvement in behavioral research: scale development and
      validation.
AB  - The construct of involvement has been found to influence brand loyalty, product
      information search processing, responses to advertising communications, diffusion
      of innovations, and ultimately, product choice decisions. Traditionally,
      involvement has been defined as being a characteristic of either a product or of
      an individual. In the present research, we make an assumption that an
      individual's 'food involvement' is a somewhat stable characteristic and we
      hypothesized that involvement with foods would vary between individuals, that
      individuals who are more highly involved with food would be better able to
      discriminate between a set of food samples than would less food involved
      individuals, and that this discrimination would operate both in affective and
      perceptive relative judgments. Using standard scale construction techniques, we
      developed a measure of the characteristic of food involvement, based on
      activities relating to food acquisition, preparation, cooking, eating and
      disposal. After several iterations, a final 12-item measure was found to have
      good test-retest reliability and internal consistency within two subscales. A
      behavioral validation study demonstrated that measures of food involvement were
      associated with discrimination and hedonic ratings for a range of foods in a
      laboratory setting. These findings suggest that food involvement, as measured by
      the Food Involvement Scale, may be an important mediator to consider when
      undertaking research with food and food habits.

PMID- 12798782
TI  - Nutrition, brain function and cognitive performance.
AB  - Military interest in the effects of nutritional factors on cognitive function has
      stimulated considerable research on a variety of food constituents. This paper
      will review the research on the amino acids tryptophan and tyrosine, caffeine and
      carbohydrate. It will focus on research that addresses the potential utility of
      these compounds in military applications, particularly the acute, as opposed to
      chronic, effects of these substances on cognitive functions such as alertness,
      vigilance and resistance to stress. Caffeine, the most intensively studied food
      constituent, has unequivocal beneficial effects on vigilance, and in sleep
      deprived individuals it enhances other cognitive functions as well. Tryptophan,
      although it clearly has sedative-like properties, has not been extensively
      studied by military laboratories for use as a hypnotic, due to safety concerns.
      Tyrosine has been examined in animal models and human studies, and appears to
      prevent the substantial decline in various aspects of cognitive performance and
      mood associated with many kinds of acute stress. Carbohydrate supplementation
      appears to enhance cognitive performance in soldiers engaged in sustained,
      intense physical activities that expend high levels of energy.

PMID- 12798783
TI  - Diet and physical performance.
AB  - This paper provides a historical summary of military nutrition research into the
      role of diet for sustaining soldier physical performance. Studies of underfeeding
      document that physical performance is preserved during several days of
      underfeeding provided sufficient carbohydrate and minerals are consumed to
      minimize the diuresis associated with semi-starvation diets and serial intake of
      carbohydrate is available to support metabolism during prolonged work. The
      Military Recommended Dietary Allowances, AR 40-25, currently recommends that when
      restricted rations are required, that the ration contain at least 1,100-1,500
      kcal, 50-70 g of protein, and a minimum of 100 g of carbohydrate on a daily
      basis. This low energy diet, however, is not recommended for subsistence for
      longer than 10 consecutive days. Dietary carbohydrate intakes of approximately
      300-400 g will more closely match the quantity of carbohydrate oxidized to meet
      daily energy requirements during field operations. Research into the potential
      advantages of dietary supplements has generally not proved advantageous when
      compared to eating a well balanced diet. Future investigations of the role of
      diet for sustaining soldier health and performance should be directed toward a
      better understanding of the influence of energy intake and macro-nutrient
      composition for preserving lean body mass, reducing susceptibility to illness and
      injury and enhancing recovery during and after sustained operations.

PMID- 12798784
TI  - Sex differences in fruit and vegetable intake in older adults.
AB  - Fruits and vegetables are important components of a healthy diet, but intakes in
      most Western countries are well below the recommended five servings a day. Men in
      particular are eating too little. The aim of this study is to understand the
      processes underlying this gender difference. Fruit and vegetable intake,
      nutrition knowledge, taste preferences, attitudes to fruit and vegetable intake,
      and dieting status, were assessed in a simple questionnaire in 1,024 older adults
      attending population-based cancer screening across the UK. The results confirmed
      the pattern of men consuming fewer servings of fruit and vegetables daily than
      women (2.52 vs 3.47; p<0.01). Fewer men than women knew the current
      recommendations for fruit and vegetable intake, and fewer were aware of the links
      between fruit and vegetable consumption and disease prevention. Women rated their
      liking for vegetables but not fruit higher, and there were no differences in
      attitudes. Men were less likely to be dieting to lose weight. Multivariate
      analysis showed that the gender difference in intake was substantially attenuated
      by controlling for nutrition knowledge. There were no significant attenuating
      effects of preferences, attitudes or dieting status. These results indicate that
      men's poorer nutrition knowledge explains a significant part of their lower
      intake of fruit and vegetables.

PMID- 12798785
TI  - Salt conditions a flavor preference or aversion after exercise depending on NaCl
      dose and sweat loss.
AB  - Sodium supplementation during or after exertion improves hydration. We
      hypothesized that it may therefore improve well being after exercise-induced
      sodium loss. To avoid cognitive-biased interpretations of the taste of salt, we
      used untasted salt in swallowed capsules to condition preference for the flavor
      of a drink. In four 90 min exercise sessions, 2-3 days apart, participants drank
      100 ml of a novel drink and swallowed a capsule, either empty (placebo), or
      containing 200, 400 or 600 mg NaCl (n=20 in each group). We found both increases
      and decreases in flavor preference conditioning, depending on salt dose and level
      of sweat loss: in groups receiving salt supplementation, high levels of sweat
      loss induced greater flavor conditioning of preference than low levels of
      sweating. However, 600 mg NaCl conditioned a flavor aversion relative to placebo,
      which was greater in exercisers sweating little. We conclude that since untasted
      salt conditioned flavor preference in direct proportion to the amount of sweat
      lost, replenishment of the sodium lost in sweat induces a rewarding physiological
      state. The results provide further evidence for the physiological determinants of
      human salt appetite, and buttress the evidence that post-ingestive effects
      condition food preferences. Conditioned flavor preference may also provide a
      useful measure of the benefits of other nutrient additives in sports drinks.

PMID- 12798787
TI  - Tendency toward overeating and restraint as predictors of food consumption.
AB  - Restrained eaters have repeatedly been found to overeat following a preload,
      which phenomenon is called the disinhibition effect. Remarkably, the
      disinhibition effect is only found when the restraint scale (RS) is used, and
      never when other measures of restraint, like the three-factor eating
      questionnaire (TFEQ) or the Dutch eating behavior questionnaire (DEBQ) are
      applied. Recent research has shown that tendency toward overeating appears to be
      a better predictor of food consumption than dietary restraint. The present study
      examines the predictive value of preload, tendency toward overeating and dietary
      restraint. An experiment was carried out with 209 female participants with the
      aim to evaluate whether the results of the study [Int J Eating Disorders 28
      (2000) 333] are robust. In addition to the RS, the TFEQ and DEBQ were used to
      measure restraint and tendency toward overeating. Again, no disinhibition effect
      occurred, confirming the results of the previous study. Restraint, as measured by
      the three questionnaires, was not related to food consumption. In contrast,
      tendency toward overeating was significantly related to food consumption.
      Restraint theory's contentions that dieting leads to overeating might be valid
      for only some dieters, namely those with a high tendency toward overeating.

PMID- 12798786
TI  - Body dissatisfaction in female restrained eaters depends on food deprivation.
AB  - This study investigated the effects of food deprivation on the body image in
      female restrained and unrestrained eaters. Twenty female restrained eaters and 20
      female unrestrained eaters were asked to identify their current and their ideal
      body shape by choosing them from a sample of nine female silhouettes. This test
      was conducted under three deprivational conditions: hungry, thirsty and non
      deprived (neither hungry nor thirsty). The discrepancy between the current and
      the ideal body shape-termed as body dissatisfaction-did not differ significantly
      between restrained and unrestrained eaters when thirsty or satiated. Under
      hunger, however, the restrained eaters scored a significantly larger discrepancy
      between their current and ideal body shape than the unrestrained eaters. The data
      suggest that women with restrained eating behavior feel a body dissatisfaction
      when being hungry.

PMID- 12798788
TI  - Dimensions of novelty: a social representation approach to new foods.
AB  - Social representations of new foods were examined with a total of 44 subjects in
      nine focus groups. Each group was homogenous, defined by age, gender and
      educational background. Halfway through the interview, commercial packages of
      functional, genetically modified, organic, nutritionally modified and ethnic
      foods were presented as visual stimuli for discussion. Thematic and content
      analyses of the interview data showed that five dichotomies characterized the
      social representation: trust/distrust, safe/unsafe, natural/artificial,
      pleasure/necessity, and past/present. Many metaphors were used, with functional
      products being associated metaphorically with, for example, medicine and
      genetically modified products being associated with death and terrorism.
      Chronological references focused on the development of cuisine. The perceived
      unsafety of new foods was an important argument for women but not for men. The
      difference between age groups was in relating the discussion to either present
      time (young subjects) or past time (older subjects). Level of education affected
      the content of argumentation. In the context of new foods, social representations
      are formed to cope with the feeling of strangeness evoked by the novelties. They
      also have a role in cultural acceptance of new products by making them familiar.
      Overall, the results reflect the development of a new common sense in which
      popularized scientific notions are anchored in the process of urbanization.

PMID- 12798789
TI  - Macronutrient effects on satiety and binge eating in bulimia nervosa and binge
      eating disorder.

PMID- 12798791
TI  - Reduction in excess daytime sleepiness by modafinil in patients with myotonic
      dystrophy.
AB  - Patients with myotonic dystrophy frequently suffer from excess daytime
      sleepiness, which can be a significant cause of disability. Previous studies have
      indicated that this excess daytime sleepiness is only occasionally due to
      obstructive sleep apnoea and may be principally of central nervous system origin.
      Modafinil has been successfully used to treat narcolepsy, a central disorder
      causing excess daytime sleepiness. We have investigated the use of this drug in
      myotonic dystrophy patients with excess daytime sleepiness. Patients were
      recruited from a clinic population on the basis of screening with the Epworth
      Sleepiness Scale. Patients scoring 10 and above were invited to participate in a
      randomized double-blind crossover trial of modafinil versus placebo, with four
      weeks in each arm of the study separated by a 2-week washout period. Patients
      were assessed by polysomnography at baseline. The primary outcome measures were
      change in both the Epworth Sleepiness Scale and a modified Maintenance of
      Wakefulness Test, which were measured at the start of each arm of the trial and
      in week 3 of each intervention period. In agreement with previous smaller
      studies, sleepiness is not correlated with CTG expansion size. Treatment with
      modafinil showed a non-significant reduction in median Epworth Sleepiness Scale.
      However, the median Maintenance of Wakefulness Test score was prolonged by
      treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac
      effects of the drug in this group of patients (resting 12 lead and 24 h ECG
      monitoring). Selected patients with myotonic dystrophy and excess daytime
      sleepiness may benefit from modafinil. In this patient group the Epworth
      Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the
      potential for cardiac disease in these patients, the drug was well tolerated with
      no adverse effects.

PMID- 12798792
TI  - Inhibition of dystroglycan cleavage causes muscular dystrophy in transgenic mice.
AB  - Dystroglycan (DG) is an essential component of the dystrophin-glycoprotein
      complex, a molecular scaffold that links the extracellular matrix to the actin
      cytoskeleton. Dystroglycan protein is post-translationally cleaved into alpha
      dystroglycan, a highly glycosylated peripheral membrane protein, and beta
      dystroglycan, a transmembrane protein. Despite clear evidence of the importance
      of dystroglycan and its associated proteins in muscular dystrophy, the purpose of
      dystroglycan proteolysis is unclear. By introducing a point mutation at the
      normal site of proteolysis (serine 654 to alanine, DGS654A), we have created a
      dystroglycan protein that is severely inhibited in its cleavage. Transgenic
      expression of DGS654A in mouse skeletal muscles inhibited the expression of
      endogenously cleaved dystroglycan, while overexpression of wild type dystroglycan
      by similar amounts did not. DGS654A animals had increased serum creatine kinase
      activity and most muscles had increased numbers of central nuclei. Overexpression
      of wild type dystroglycan, by contrast, caused no dystrophy by these measures.
      Dystrophy in DGS654A muscles correlated with reduced binding of antibodies that
      recognize glycosylated forms of alpha dystroglycan. Lastly, neuromuscular
      junctions in DGS654A muscles were aberrant in structure. These data show that
      aberrant processing of the dystroglycan polypeptide causes muscular dystrophy and
      suggest that dystroglycan processing is important for the proper glycosylation of
      alpha dystroglycan.

PMID- 12798793
TI  - Consequence of parvalbumin deficiency in the mdx mouse: histological, biochemical
      and mechanical phenotype of a new double mutant.
AB  - We tested the hypothesis whether the mild dystrophy in mdx mice could result from
      the contribution of the cytosolic calcium buffer parvalbumin in maintaining a
      normal cytosolic [Ca2+]i, in spite of an increased passive Ca2+ influx. By
      crossing mdx mice with parvalbumin-deficient mice, double mutant mice, lacking
      both dystrophin and parvalbumin, were obtained. Though resting cytosolic [Ca2+]i
      and total calcium content were similar to that of mdx muscles, this new animal
      model presented a slightly more severe phenotype than the mdx mouse. Muscle
      pseudo-hypertrophy, the density of myotubes and of centronucleated fibres as well
      as the loss of IIB fibres were all increased in parvalbumin-deficient mdx mice.
      Many of these deficits were overcome in late adulthood, albeit fibrosis was
      clearly more pronounced than in mdx muscles. At 90 days, parvalbumin-deficient
      mdx mice showed higher levels of creatine phosphokinase and lower muscle
      strength, in vivo, than mdx mice. Isometric tension of isolated muscle was
      reduced, but the susceptibility to eccentric contraction was not increased. The
      slight aggravation of muscle dystrophy observed in mdx mice deprived of
      parvalbumin cannot explain the severity of the affection observed in xmd dogs and
      Duchenne dystrophy patients where parvalbumin is constitutively not expressed.

PMID- 12798794
TI  - Correlated NOS-Imu and myf5 expression by satellite cells in mdx mouse muscle
      regeneration during NOS manipulation and deflazacort treatment.
AB  - Satellite cells, muscle precursor cells in skeletal muscle, are normally
      quiescent and become activated by disease or injury. A lack of dystrophin and
      changes in the expression or activity of neuronal nitric oxide synthase (NOS-I)
      affect the timing of activation in vivo. Nitric oxide synthase inhibition delays
      muscle repair in normal mice, and worsens muscular dystrophy in the mdx mouse, a
      genetic homologue of Duchenne muscular dystrophy. However, the potential role of
      activation and repair events mediated by nitric oxide in determining the outcome
      of steroid or other treatments for muscular dystrophy is not clear. We tested the
      hypothesis that the extent of repair in dystrophic muscles of mdx mice is partly
      dependent on NOS-Imu expression and activity. Myotube formation in regenerating
      muscle was promoted by deflazacort treatment of mdx dystrophic mice (P<0.05), and
      improved by combination with the nitric oxide synthase substrate, L-arginine,
      especially in the diaphragm. NOS-Imu mRNA expression and activity were present in
      satellite cells and very new myotubes of regenerating and dystrophic muscle.
      Deflazacort treatment resulted in increased NOS-Imu expression in regenerating
      muscles in a strong and specific correlation with myf5 expression (r=0.95,
      P<0.01), a marker for muscle repair. Nitric oxide synthase inhibition prevented
      the deflazacort-induced rise in NOS-Imu and myf5 expression in the diaphragm
      without affecting the diameter of non-regenerating fibres. These in vivo studies
      suggest that gains in NOS-Imu expression and nitric oxide synthase activity in
      satellite cells can increase the extent and speed of repair, even in the absence
      of dystrophin in muscle fibres. NOS-Imu may be a useful therapeutic target to
      augment the effects of steroidal or other treatments of muscular dystrophy.

PMID- 12798795
TI  - Assessing gene and cell therapies applied in striated skeletal and cardiac
      muscle: is there a role for nuclear magnetic resonance?
AB  - Gene and cell therapies convey high hopes for treatment of skeletal and heart
      muscle diseases. In the experimental protocols under development as well as in
      the first clinical trials, longitudinal control by an atraumatic procedure is
      needed. Nuclear magnetic resonance (NMR), via its two modalities, imaging or
      spectroscopy, should play a major role both for in vivo animal and human studies,
      because of the great number of parameters that can be measured, sequentially or
      simultaneously, and because of its aptitude to monitor several steps of
      protocols, in particular to detect physiological modifications induced by
      therapies. We review here the many possible applications of nuclear magnetic
      resonance in gene/cell therapies where muscle is the target organ, with emphasis
      on the application of nuclear magnetic resonance to functional studies.

PMID- 12798796
TI  - Expression of mouse agrin in normal, denervated and dystrophic muscle.
AB  - Agrin is a heparan sulfate proteoglycan that is required for the development of
      postsynaptic specializations at the neuromuscular junction. An alternatively
      spliced isoform of agrin that lacks this activity is found in basement membranes
      of several tissues including embryonic muscle. Overexpression of a miniaturized
      form of this agrin isoform ameliorates the severe muscle dystrophy of laminin
      alpha2-deficient mice, a mouse model for merosin-deficient congenital muscle
      dystrophy. Several lines of evidence indicate that this amelioration is based on
      the high-affinity binding of the mini-agrin to the laminins and to alpha
      dystroglycan. Here, we used antibodies raised against mouse agrin to evaluate
      protein expression in adult muscle of normal and dystrophic mice. We find that
      expression of agrin in non-synaptic region varies greatly between different
      muscles in wild-type mice and that its levels are altered in dystrophic muscle.

PMID- 12798797
TI  - Two pathogenic mutations in the mitochondrial DNA tRNA Leu(UUR) gene (T3258C and
      A3280G) resulting in variable clinical phenotypes.
AB  - We studied two patients with ragged-red fibers and combined defects of the
      mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial
      encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a
      T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus
      cardiomyopathy and had an A3280G mutation in the same gene. Both mutations were
      heteroplasmic, abundant in muscle of the patients, less abundant in blood, and
      still less abundant in blood from their maternal relatives. In both patients,
      single muscle fiber analysis revealed greater abundance of mutant genomes in
      ragged-red fibers than in normal fibers, supporting the pathogenicity of both
      mutations.

PMID- 12798799
TI  - 'Quantitative assessment of calf circumference in Duchenne muscular dystrophy
      patients'.

PMID- 12798798
TI  - Berengario da Carpi, a pioneer in anatomy, rediscovered by Vittorio Putti.

PMID- 12798802
TI  - A history of heredity: the wider perspective.

PMID- 12798803
TI  - Out of the warm little pond: prerequisites for an evolvable system.

PMID- 12798808
TI  - Parents and children: ideas of heredity in the 19th century.
AB  - The concept of heredity played a powerful role in structuring 19th-century
      debates over sickness, morality, class, race, education, social change and
      evolution. But there was very little agreement as to which qualities were
      heritable and how new hereditary variants were acquired. In consequence, notions
      of heredity existed in a wide variety of forms, expressing anything from extreme
      determinism and a belief in the incorrigibility of individuals, social and racial
      groups, to unleavened optimism, and a faith in ultimate human perfectibility.
      This article explores these rich hereditarian discourses to convey an impression
      of a century that was at least as preoccupied with the concept of biological
      inheritance as we are today.

PMID- 12798809
TI  - Fertility or sterility? Darwin, Naudin and the problem of experimental hybridity.
AB  - Darwin came to realize that he could never devise an experiment that would
      demonstrate the development of new species by crossing hybrids. Instead, he
      turned to the problem of sterility within a species. The difference between
      Darwin's experimental and theoretical approach and that of French scientists
      working in the Museum d'Histoire Naturelle in Paris can be shown most vividly by
      tracking Darwin's experiments in botany and his interest in those of Charles
      Naudin on hybrid plants. In his discussion of Mendel, Robert Olby has provided an
      interesting analysis of Naudin's hereditary concepts. I have approached some of
      the same work here with an emphasis on the question of sterility raised by
      Darwin, not simply between hybrids but within members of the same species and the
      light that he thought this could throw on both heredity and the origin of
      species.

PMID- 12798810
TI  - Mendel and modern genetics: the legacy for today.
AB  - The legacy of Mendel's pioneering studies of hybridization in the pea continues
      to influence the way we understand modern genetics. But what sort of picture did
      Mendel himself have of his work and its ultimate uses, and how does that picture
      compare with the collection of ideas and methodologies that was put forward in
      his name and later became known as 'Mendelism'? With genetics standing at the
      center of our present biomedical and biotechnological research, an examination of
      the history of our concepts in the field can help us better understand what we
      should and should not expect from current genetic claims. For that enterprise
      there is no better starting place than Mendel himself.

PMID- 12798811
TI  - Darlington and the 'invention' of the chromosome.
AB  - Cyril Dean Darlington (1903-1981) has been forgotten by historians, but was in
      his day, the leading cytologist of the premolecular era. Of humble and
      inconspicuous beginnings, Darlington started his career as an unpaid volunteer
      worker under the aging William Bateson. Working in almost total isolation and
      with no scientific guidance, he boldly deduced the laws of chromosome behaviour,
      making cytology relevant once again both to genetics and to evolutionary theory.
      This process did not proceed smoothly, for both Darlington's method, and cross
      disciplinary approach made the reception of his novel ideas difficult. This
      article examines Darlington's contribution to the premolecular understanding of
      Life, and the reasons why it was so difficult to accept.

PMID- 12798812
TI  - Relics, replicas and commemorations.
AB  - Several replicas of Watson and Crick's demonstration model of DNA built at the
      Cavendish Laboratory in Cambridge in 1953 exist, but where is the original? Once
      the object of intense discussion but soon superseded by more refined models built
      at King's College London, it slowly fell to pieces and was eventually
      disassembled. Twenty years after it was first constructed, some of its pieces
      resurfaced at Bristol. By that time, the value attached to the original
      incarnation of the double helix had changed substantially, and the Science Museum
      in London commissioned a replica of the model, with some of the original parts
      built into it. The model was hailed as 'the nearest there is to the original'. It
      has since served as prototype for further replicas. Meanwhile the spidery model
      of DNA has become the ultimate icon of 20th-century life sciences, and more
      pieces supposedly belonging to the original continue to appear at auction.

PMID- 12798813
TI  - Why celebrate the golden jubilee of the double helix?
AB  - This year, widespread attention has been bestowed upon the discovery of the
      Watson-Crick model of DNA. This extensive publicity contrasts with the sparse
      news coverage it received in 1953, when war-torn Britain was celebrating the
      coronation of Queen Elizabeth and the first ascent of Mount Everest. The
      remarkable growth of molecular biology since 1953 is the chief reason for the
      attention given to the Watson-Crick model today.

PMID- 12798814
TI  - Pictures of Dorothy Hodgkin.
AB  - There are no established conventions for portraying scientific women. At the
      Royal Society, the first image of a female scientist was Henry Moore's drawing of
      Dorothy Hodgkin's hands, cruelly twisted by agonising arthritis. In her famous
      oil portrait, Maggi Hambling also focuses on Hodgkin's hands, thus symbolising
      the Nobel-prize winner's dedication to research and the importance of manual
      dexterity. Although Hambling's picture features a model of insulin, it is very
      different from photographs celebrating the discovery of DNA.

PMID- 12798815
TI  - Sequencing the genome from nematode to human: changing methods, changing science.
AB  - The history of science tends to be recounted as a story of progress from early
      goals and discoveries to a unified outcome, in some sense implicit from the
      beginning, and often due to technological advances. The sequencing of the human
      genome is no exception. As a crucial part of the Human Genome Project, the
      history of genomic sequencing is typically presented as a direct result of the
      discoveries of the structure of DNA and its coding function, together with
      practical factors such as the development of techniques which made large-scale
      sequencing possible. However, the history of sequencing is inevitably a more
      complicated story, not only about molecular biology, but also about the evolving
      culture of scientific practice at the end of the 20th century.

PMID- 12798816
TI  - God's signature: DNA profiling, the new gold standard in forensic science.
AB  - In the mid-1980s, when the first DNA profiling techniques were developed, the
      name DNA 'fingerprinting' was widely used. At the time, fingerprinting was a well
      established forensic method, and it was rarely questioned in the courts.
      Fingerprint examiners were permitted to describe matching prints as evidence of
      individual identity, and they were not required to give probability estimates.
      Despite its nominal association with the older technique, DNA 'fingerprinting'
      went through a period of controversy, especially in the US courts. The
      association with fingerprinting was questioned, and experts were required to
      qualify their testimony with probability figures. Heated debate occurred in
      scientific publications and law courts about the statistical and population
      genetic assumptions that went into the probability calculations presented in
      court cases. However, by the late 1990s DNA profiling was so widely accepted that
      it became a basis for invidious comparison with all other forms of forensic
      evidence, including fingerprinting. In the past three years, the admissibility of
      fingerprint evidence has been challenged in several US federal and state courts.
      This article discusses the socio-legal and socio-technical issues that led to the
      inversion of credibility that characterized the intertwined history of the two
      techniques.

PMID- 12798817
TI  - Heart failure management programs: how far should we go?

PMID- 12798818
TI  - The non-invasive assessment of hibernating myocardium in ischaemic cardiomyopathy
      -a myriad of techniques.
AB  - Heart failure is placing an ever-increasing burden on society. Many subjects with
      heart failure and underlying coronary artery disease have a significant amount of
      akinetic but viable myocardium that is able to contract should myocardial
      perfusion improve (hibernating myocardium). Non-randomised studies have shown
      prognostic benefit in subjects with hibernating myocardium undergoing
      revascularisation. Several non-invasive techniques have been developed to assess
      the presence or absence of hibernating myocardium. This review will examine the
      epidemiology and underlying pathogenesis of hibernating myocardium; evaluate the
      non-invasive techniques for diagnosing hibernating myocardium, and look at
      therapeutic intervention in subjects with hibernating myocardium.

PMID- 12798819
TI  - Role of nitric oxide in posthypoxic contractile dysfunction of diabetic
      cardiomyopathy.
AB  - We investigated the role of nitric oxide synthase (NOS) in the contractile
      dysfunction of diabetic cardiomyopathy, comparing streptozotocin-treated (60
      mg/kg) diabetic Wistar rats with matched non-diabetic controls. Isolated
      isovolumic heart function was studied during normoxia and in response to brief
      hypoxia-reoxygenation. Diabetic hearts had significantly lower left-ventricular
      pressure and slower isovolumic relaxation than controls (relaxation time
      constant, T 40.2+/-2.3 vs. 27.7+/-0.9 ms; P<0.05) and a blunted response to
      hypoxia. These abnormalities were unaffected by NOS inhibition. Upon
      reoxygenation after brief hypoxia, diabetic hearts exhibited substantial
      worsening of LV relaxation compared to normal hearts (T 69.1+/-3.3 vs. 56.6+/-7.9
      ms; P<0.05). This post-hypoxic diastolic dysfunction was significantly attenuated
      either by the non-selective NOS inhibitor L-NAME, the iNOS inhibitor L-NIL, or
      the reactive-oxygen-species (ROS) scavenger thiourea. Only diabetic hearts
      expressed iNOS protein, whereas eNOS expression was similar in both groups. In
      conclusion, diabetic hearts exhibit markedly abnormal post-hypoxic relaxation,
      which is attributable to both ROS and NO derived from iNOS.

PMID- 12798820
TI  - Effects of diuretic treatment on cardiac and circulating RAS in chronic heart
      failure post-myocardial infarction in rats.
AB  - BACKGROUND: Cardiac angiotensin converting enzyme (ACE) is activated by an
      increase in wall stress and is involved in remodeling processes. Heart failure is
      often treated with ACE inhibitors and diuretics although diuretic treatment could
      activate the renin-angiotensin system (RAS). AIMS: To examine the effects of
      diuretic treatment on cardiac and circulating RAS in post-infarction chronic
      heart failure. METHODS: Myocardial infarction was produced by coronary artery
      ligation in spontaneously hypertensive rats. The rats were randomly assigned to
      receive either ramipril (1 mg/kg/day), furosemide (4 mg/kg/day), or combination
      therapy for 6 weeks, commencing 2 weeks after infarction. RESULTS: All three
      treatment protocols equivalently attenuated reactive hypertrophy of the right
      ventricle and ventricular septum and improved left ventricular systolic function.
      Both cardiac ACE mRNA and activity were significantly increased in untreated
      rats. This increase was attenuated by both ramipril and furosemide and further
      depressed by the combination. The increase in activity was completely inhibited
      by either agent alone. Plasma renin activity was upregulated by ramipril or
      ramipril plus furosemide but not influenced by infarction or furosemide alone.
      CONCLUSIONS: Furosemide and ramipril significantly reduced cardiac ACE and
      remodeling. Diuretics work favorably and do not interfere with the effects of ACE
      inhibitors. Possibly, a reduction in wall stress due to decreased volume overload
      accounts for the effects of diuretics on cardiac ACE in the treatment of post
      infarction remodeling in hypertensive hearts. These data suggest a new mechanism
      for the frequently observed beneficial effect of diuretics in heart failure.

PMID- 12798821
TI  - Prognostic value of 6-minute walk corridor test in patients with mild to moderate
      heart failure: comparison with other methods of functional evaluation.
AB  - AIM: The study was designed to evaluate the prognostic value of the 6-min walk
      test (6MWT) in patients with mild to moderate congestive heart failure (CHF).
      METHODS AND RESULTS: Two hundred and fourteen patients (119 men and 95 women,
      mean age 64 years) were followed for a mean period of 34 months to assess event
      free survival (death, heart transplantation). Sixty-six patients (34%) died (63
      cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart
      transplantation. For patients who walked <300 m during the 6MWT, survival was 62%
      compared with 82% in patients who walked 300-450 m or>450 m. With univariate
      analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001),
      aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT
      distance (P<0.01) were all significantly related to survival. No significant
      relationship was found between survival, peak oxygen consumption or anaerobic
      threshold. Multivariate analysis using the Cox-stepwise regression model showed
      that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the
      strongest prognostic markers. CONCLUSION: A 6MWT distance of <300 m is a simple
      and useful prognostic marker of subsequent cardiac death in unselected patients
      with mild to moderate CHF.

PMID- 12798822
TI  - Central hemodynamic responses during serial exercise tests in heart failure
      patients using implantable hemodynamic monitors.
AB  - INTRODUCTION: Exercise testing is commonly used in patients with congestive heart
      failure for diagnostic and prognostic purposes. Such testing may be even more
      valuable if invasive hemodynamics are acquired. However, this will make the test
      more complex and expensive and only provides information from isolated moments.
      We studied serial exercise tests in heart failure patients with implanted
      hemodynamic monitors allowing recording of central hemodynamics. METHODS: Twenty
      one NYHA Class II-III heart failure patients underwent maximal exercise tests and
      submaximal bike or 6-min hall walk tests to quantify their hemodynamic responses
      and to study the feasibility of conducting exercise tests in patients with such
      devices. RESULTS: Patients were followed for 2-3 years with serial exercise
      tests. During maximal tests (n=70), heart rate increased by 52+/-19 bpm while
      S(v)O(2) decreased by 35+/-10% saturation units. RV systolic and diastolic
      pressure increased 29+/-11 and 11+/-6 mmHg, respectively, while pulmonary artery
      diastolic pressure increased 21+/-8 mmHg. Submaximal bike (n=196) and hall walk
      tests (n=172) resulted in S(v)O(2) changes of 80 and 91% of the maximal tests,
      while RV pressures ranged from 72 to 79% of maximal responses. CONCLUSIONS: An
      added potential value of implantable hemodynamic monitors in heart failure
      patients may be to quantitatively determine the true hemodynamic profile during
      standard non-invasive clinical exercise tests and to compare that to hemodynamic
      effects of regular exercise during daily living. It would be of interest to study
      whether such information could improve the ability to predict changes in a
      patient's clinical condition and to improve tailoring patient management.

PMID- 12798823
TI  - Clinical features and contemporary management of patients with low and preserved
      ejection fraction heart failure: baseline characteristics of patients in the
      Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity
      (CHARM) programme.
AB  - AIMS: To describe the clinical characteristics and contemporary treatment of a
      broad spectrum of patients with chronic heart failure (CHF) randomised in the
      Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity
      (CHARM) programme, consisting of three component studies comparing placebo to
      candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM
      Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE
      inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and
      3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more
      often female. The proportion of women in CHARM Preserved was 40% compared to 32%
      in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were
      also more often hypertensive than in the other two trials (64% vs. 50% and 48%,
      respectively). Symptoms and signs (with the exception of a third heart sound)
      were similar in all three patient groups. Beta-blockers were used in over half of
      patients in all three groups. Digoxin and spironolactone were used less
      frequently and calcium antagonists more frequently in CHARM Preserved.
      Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE
      inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the
      largest and most detailed comparison to date of patients low- and preserved-LVEF
      CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort
      of patients and the other treatment which these patients receive.

PMID- 12798825
TI  - Beta-blocker benefit according to severity of heart failure.
AB  - BACKGROUND AND AIMS: Beta-blockers are an established treatment for chronic heart
      failure. However, the relationship between their benefit and the severity of the
      disease remains to be determined. METHODS AND RESULTS: We studied the
      relationship between amplitude of benefit of beta-blockers and severity of
      chronic heart failure, based on data for mortality and hospitalizations for
      worsening heart failure, using a meta-analysis of randomized controlled trials,
      complementary subgroup analyses and analysis of individual data from the CIBIS II
      trial. In the meta-analysis, mortality was reduced by 22% (95%CI: 16 to 28) and
      hospitalizations for worsening heart failure by 24% (95%CI: 20 to 29). Benefit
      was similar with metoprolol, bisoprolol and carvedilol. After exclusion of
      bucindolol trials, due to the heterogeneity of results for mortality, the
      reduction in mortality was similar according to the severity of heart failure,
      assessed either by left ventricular ejection fraction or by New York Heart
      Association classification. In CIBIS II, beta-blockers induced a significant
      reduction in mortality of 45% (95%CI: 9 to 66), 41% (95%CI: 17 to 59) and 23%
      (95%CI: 1 to 40) in the low, intermediate and high risk groups, respectively.
      Hospitalizations were reduced by 35% (95%CI: 2 to 57), 41% (95%CI: 18 to 58) and
      23% (95%CI: 0 to 41), there was no significant difference between the three score
      groups. CONCLUSION: We conclude that the amplitude of benefit of the beta
      blockers carvedilol, metoprolol and bisoprolol on mortality and morbidity is
      similar, regardless of the severity of chronic heart failure.

PMID- 12798824
TI  - Aspirin alters arterial function in patients with chronic heart failure treated
      with ACE inhibitors: a dose-mediated deleterious effect.
AB  - BACKGROUND: By inhibiting prostaglandin synthesis, aspirin can interfere with
      both arterial functional and angiotensin-converting enzyme inhibitor (ACEI)
      properties and be deleterious in chronic heart failure (CHF). AIM: Our aim was to
      prospectively evaluate the effect of aspirin on arterial functional properties in
      CHF patients treated with ACEIs. METHODS AND RESULTS: Over three consecutive
      treatment periods of 7 days, 18 patients received placebo, followed by aspirin
      100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of
      reflected wave and time reflection by radial applanation tonometry; pulse wave
      velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and
      urine was performed. Aspirin 325 mg/day induced a significant increase in
      augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and
      aspirin 100 mg, respectively) and a significant decrease in reflected wave
      traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar,
      though non-significant, trend in these parameters compared with placebo. Both
      aspirin treatments produced a statistically significant decrease in serum TxB2
      (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2
      (P=0.136). CONCLUSION: This study demonstrates the existence of a dose-mediated
      deleterious effect of aspirin upon arterial functional properties in CHF patients
      treated with ACEI.

PMID- 12798826
TI  - The prognostic importance of heart failure and age in patients treated with
      primary angioplasty.
AB  - BACKGROUND: Effective risk stratification is essential in the management of
      patients with acute myocardial infarction. Available models have not yet been
      studied and validated in patients treated with primary angioplasty for acute
      myocardial infarction. METHODS: The prognostic value of heart failure defined by
      Killip class and age upon admission and the impact of success and failure of the
      angioplasty procedure was studied in 1702 consecutive patients treated with
      primary angioplasty. FINDINGS: The combination of Killip class and age is a
      strong predictor of 30-day mortality and categorizes patients in subgroups with
      30-day mortality risk ranging from 0.5 to 70%. Angioplasty failure results in a
      high 30-day mortality, in particular in patients with Killip class > or =II
      and/or age > or =70 years. A large majority of patients (72%), characterized by
      Killip class I and age <70 years, can be identified with a 0.5% risk of death at
      30 days. INTERPRETATION: The presence of heart failure (Killip class) and age
      predicts 30-day mortality in patients on their way to the catheterization
      laboratory for primary angioplasty. This simple and effective early risk
      stratification, in combination with success and failure of the primary
      angioplasty, can be used to direct subsequent patient management.

PMID- 12798828
TI  - Simultaneous vs. sequential biventricular pacing in dilated cardiomyopathy: an
      acute hemodynamic study.
AB  - AIMS: Simultaneous biventricular pacing improves left ventricular (LV) systolic
      performance in patients with dilated cardiomyopathy and intraventricular
      conduction delay. We tested the hypothesis that further improvements can be
      obtained using sequential biventricular pacing by optimizing both
      atrioventricular and interventricular delays. METHODS AND RESULTS: In 12
      patients, LV pressure, right ventricular (RV) pressure and respective rates of
      change of pressure (dP/dt) were acutely measured during biventricular pacing with
      different atrioventricular and interventricular (VVi) intervals ranging from -60
      to +40 ms. The average increase vs. baseline in maximum LV dP/dt was higher for
      sequential than for simultaneous biventricular pacing (VDD mode: 35+/-20 vs. 29+/
      18%, P<0.01; DDD mode: 38+/-23 vs. 34+/-25%, P<0.01), with a minority of patients
      accounting for most of the difference. The mean optimal VVi was -25+/-21 ms in
      VDD mode and -25+/-26 ms in DDD mode. With these settings, RV dP/dt was not
      significantly different from baseline. QRS shortening was not predictive of LV
      dP/dt increase. CONCLUSION: A significant increase of LV dP/dt with no change in
      RV dP/dt can be obtained by sequential biventricular pacing as compared to
      simultaneous biventricular pacing. The highest LV dP/dt is achieved when LV is
      stimulated before RV. The hemodynamic advantage might be of clinical significance
      in selected cases.

PMID- 12798827
TI  - The heart failure revascularisation trial (HEART): rationale, design and
      methodology.
AB  - BACKGROUND: Most patients with heart failure due to left ventricular systolic
      dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of
      myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is
      not known whether revascularisation in such cases is safe or beneficial. AIMS: To
      determine whether revascularisation will improve the survival of patients with
      LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This
      is a randomised controlled trial comparing revascularisation or not, in addition
      to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone
      antagonists and an anti-thrombotic agent. Patients must have heart failure
      requiring treatment with diuretics, a left ventricular ejection fraction <35% and
      evidence of coronary disease. Myocardial viability and ischaemia are assessed by
      a broad range of techniques including stress echocardiography and nuclear
      imaging. All imaging tests are reviewed in core laboratories to ensure uniform
      reporting. Any conventional revascularisation technique is permitted. The primary
      outcome measure is all cause mortality. Symptoms, quality of life and health
      economic issues will also be explored. Assuming an annual mortality of 10% in the
      control group and allowing for substantial cross-over rates, a study of 800
      patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to
      show a 25% reduction in mortality with revascularisation. RESULTS: At the time of
      writing 180 patients have been screened for inclusion, 111 have consented to
      participate and 70 have been randomised. The results of viability testing are
      awaited in 22 patients. Twenty-six patients had been investigated for myocardial
      viability and/or by angiography prior to consent, as part of the routine practice
      in that cardiology department. Of 68 patients who have completed assessment only
      after consent, 47 (69%) were included. The principal reason for drop-out between
      consent and randomisation was lack of evidence of myocardial ischaemia or
      hibernation. CONCLUSION: The HEART trial will help to determine whether
      investigation of myocardial ischaemia and/or viability with a view to
      revascularisation should become part of the routine care of patients with heart
      failure due to LVSD and CAD.

PMID- 12798829
TI  - Eligibility for biventricular pacing in patients with an implantable cardioverter
      defibrillator.
AB  - Implantable cardioverter defibrillator (ICD)-therapy prevents sudden death in
      patients at high risk, but incidence of death due to heart failure remains
      unaltered. Recent data suggest that biventricular (BV) pacing is useful in
      patients with heart failure. It is unclear, how many patients with an ICD
      indication may have an indication for BV pacing. Therefore all patients who
      received an ICD were analyzed for eligibility of BV pacing using the following
      criteria: NYHA class III or IV, QRS duration >120 ms, depressed LVEF. Three
      hundred and ninety consecutive patients received an ICD from June 1996 to March
      2001. Underlying disease was ischemic heart disease in 66%. In the 390 patients
      the mean LVEF was 36+/-17%, 20% were in NYHA class III-IV and 16% were in NYHA
      class II with an LVEF <30%. Of these 140 patients, 79 had a QRS duration >120 ms.
      Thus, 79 (20%) patients were eligible for BV pacing in addition to ICD-therapy.
      Patients who received a BV pacemaker in addition to ICD-therapy had a superior
      survival, improved in NYHA class and showed a significantly lower hospitalization
      rate as compared to patients who received an ICD only. Screening for eligibility
      of BV pacing may be considered in patients with CHF scheduled for ICD
      implantation.

PMID- 12798830
TI  - Efficacy of a homeopathic Crataegus preparation compared with usual therapy for
      mild (NYHA II) cardiac insufficiency: results of an observational cohort study.
AB  - OBJECTIVES: To compare the efficacy of the homeopathic Crataegus preparation
      Cralonin for non-inferiority to standard treatment for mild cardiac
      insufficiency. METHODS: Multicentre non-randomised cohort study in patients aged
      50-75 years in New York Heart Association class II. Patients received Cralonin
      (n=110) or ACE inhibitor/diuretics (n=102) for 8 weeks. To adjust for confounding
      by baseline factors, populations were stratified according to propensity score.
      After adjusting, there were no statistically significant differences between
      treatment groups. Treatment efficacy was assessed on 15 variables. A stringent
      non-inferiority criterion for the upper limit of the 97.5% one-sided confidence
      interval of the treatment difference was set to 0.2x the standard deviation
      (S.D.). RESULTS: Both treatment regimens improved scores on most variables
      studied, with the greatest effect on double product after exercise (average score
      reduction 15.4% with Cralonin vs. 16.0% for the control group). Stringent non
      inferiority of Cralonin was demonstrated on 7 variables. Medium-stringent
      (0.5xS.D.) non-inferiority was indicated by 13 variables (exceptions: systolic
      blood pressure (BP) during exercise and diastolic BP at rest; for these,
      differences between treatments were not significant). Both treatments were well
      tolerated. CONCLUSION: The Crataegus-based preparation Cralonin is non-inferior
      to usual ACE inhibitor/diuretics treatment for mild cardiac insufficiency on all
      parameters except BP reduction.

PMID- 12798831
TI  - Comparing methodological quality and consistency of international guidelines for
      the management of patients with chronic heart failure.
AB  - BACKGROUND: Guidelines (GLs) for the management of heart failure (HF) are of
      great importance in order to define and disseminate therapeutic recommendations
      based on scientific evidence. The aim was to analyse and to compare the
      methodological quality of HF GLs as well as to evaluate the consistency of
      therapeutic recommendations. METHODS: Eleven international GLs for the management
      of chronic HF were identified by search of the internet, electronic databases and
      references of published literature. Their methodological quality was assessed by
      two different appraisal instruments: (1) according to the US National Guideline
      Clearinghouse (NGC) on a scale from 0 to 17 points, (2) according to the German
      Guideline Clearinghouse (Agency for Quality in Medicine, AQUMED) on a scale from
      0 to 44 points. Clinical criteria for assessment of the consistency of the
      recommendations included diagnostic testing, pharmacological and non
      pharmacological treatment. RESULTS: The quality scores of the GLs varied
      substantially with a range of 1.5-15.5 points (NGC) and 8-30 points (AQUMED). The
      greatest variation was found in the dimensions "development" and "evidence". Only
      3 of the 11 GLs (approximately 30%) were rated as methodologically well prepared.
      The recommendations on diagnostic procedures and medical management were rather
      consistent among the different GLs. CONCLUSIONS: Published international GL
      recommendations on medical management of patients with chronic HF are broadly
      consistent. The methodological quality of the GLs, however, varies to a great
      extent. Improvement is needed in most methodological aspects, especially in the
      dimensions "evidence" and "applicability".

PMID- 12798832
TI  - Differences between general practitioners and cardiologists in diagnosis and
      management of heart failure: a survey in every-day practice.
AB  - BACKGROUND: Data on diagnosis and management of heart failure in every-day care
      are scarce. AIMS: To compare general practitioners' and cardiologists' diagnostic
      work-up and management of patients with (suspected) heart failure. METHODS: In a
      cross-sectional survey we studied a sample of 103 files of patients coded as
      heart failure in primary care (31 general practices), and 99 files of out
      patients coded as heart failure from 9 hospitals in the Netherlands. We defined
      patients as heart failure "GP patients", when they were managed by a general
      practitioner without co-treatment of a cardiologist. RESULTS: Patients managed in
      general practice were older (mean age 79 years (S.D. 8.5) and more often female
      than "cardiology patients" (mean age 64 years (S.D. 11.7)). Ischaemic heart
      disease (31 vs. 57%) was more prevalent in "cardiology patients". Additional
      investigations such as chest radiography (51% vs. 84%), electrocardiography (39%
      vs. 100%), and (Doppler-) echocardiography (12% vs. 97%) were performed more
      often in "cardiology patients". Most patients received diuretics (85% vs.79%).
      Angiotensin converting enzyme inhibitors (40% vs. 76%), beta-blockers (9% vs.
      30%), spironolactone (11% vs. 32%), and angiotensin-II-antagonists (6% vs. 13%)
      were prescribed much more often to "cardiology patients". CONCLUSION: General
      practitioners more often treat elderly, female patients with heart failure than
      cardiologists. General practitioners use less additional investigations and
      prescribe less potentially beneficial medication, compared to cardiologists.
      Population characteristics only partly explain these differences, suggesting that
      the physician's attitude has an important bearing on the uptake of treatment.

PMID- 12798833
TI  - Diagnosis and management of heart failure: a questionnaire among general
      practitioners and cardiologists.

PMID- 12798834
TI  - The diagnosis of heart failure in general practice: implications for the UK
      National Service Framework.
AB  - BACKGROUND: The UK National Service Framework recommends patients with suspected
      heart failure undergo echocardiography. Selection of patients for this
      investigation in primary care is difficult. It is not clear which clinical
      features best identify patients with left ventricular systolic dysfunction. AIM:
      Using echocardiography, to establish the accuracy of primary care diagnosis of
      left ventricular systolic dysfunction. To investigate the sensitivity,
      specificity and predictive values of clinical features in the diagnosis of left
      ventricular systolic dysfunction. STUDY: A cross-sectional study of 621 patients
      from a population prescribed loop diuretics in 7 general practices. METHOD:
      Clinical diagnoses were extracted from general practice records. Symptoms,
      clinical signs, ECG features, brain natriuretic peptide levels and
      echocardiographic findings were studied in a research clinic. RESULTS: Left
      ventricular systolic dysfunction (ejection fraction <40%) was present in 50% of
      621 patients prescribed loop diuretics in primary care. General practice
      diagnoses showed high false positive rates. Individual or combinations of
      clinical features did not accurately predict left ventricular systolic
      dysfunction. CONCLUSION: These results suggest the clinical diagnosis of left
      ventricular systolic dysfunction is inaccurate in this population. General
      practitioners should have a low threshold for referring patients prescribed loop
      diuretics for echocardiography. Increased open access echocardiography facilities
      will be needed.

PMID- 12798835
TI  - Difficulties of introducing the National Service Framework for heart failure into
      general practice in the UK.
AB  - BACKGROUND: The National Service Framework (NSF) sets standards for the
      management of heart failure in the UK. Loop diuretics are commonly first
      prescribed in primary care. Some patients taking these drugs have heart failure
      and may benefit from other treatments including ACE inhibitors. Accurate
      diagnosis in primary care is essential for the aims of the NSF to be realised.
      AIMS: To investigate loop diuretic prescribing in general practice, to analyse
      recorded clinical features, patient investigations and ACE inhibitor use in this
      population. METHOD: One thousand three hundred and one patients taking loop
      diuretics were identified from prescription records of seven general practices.
      Demographic details, clinical features, investigations and drug treatments were
      extracted from patient records. RESULTS: The prevalence of loop diuretic
      prescribing increased with age. Twenty percent of patients were attributed a
      diagnosis of heart failure but relevant clinical features were recorded in less
      than 50% of patient records. Open access echocardiography was used in 8.9% of
      patients. ACE inhibitors were prescribed in 39.8% of patients considered to have
      heart failure. 18.2% of these were taking the recommended target dose.
      CONCLUSION: Loop diuretics are prescribed commonly, particularly in the elderly.
      There is no clear pattern of documented clinical features that leads to
      prescription of these drugs. Open access echocardiography is rarely used to aid
      diagnosis. ACE inhibitors are under-prescribed and under-dosed in patients
      diagnosed with heart failure in this study population.

PMID- 12798836
TI  - Development and testing of the European Heart Failure Self-Care Behaviour Scale.
AB  - BACKGROUND: Improvement of self-care behaviour is an aim of several non
      pharmacological nurse-led management programmes for patients with heart failure.
      These programmes are often evaluated based on their effects on readmission, costs
      and quality of life. It is, however, also important to know how patients changed
      their self-care behaviour as a result of such a programme. Therefore a
      comprehensive, reliable and valid measure of the self-care behaviour of HF
      patients is needed. OBJECTIVES: To develop a scale measuring the behaviour that
      heart failure patients perform to maintain life, healthy functioning, and well
      being. METHOD: The European Heart Failure Self-Care Behaviour Scale (EHFScBS) was
      developed in three phases: (1) concept analysis and first construction; (2)
      revision of items and response and scoring format; and (3) testing of the new
      scale for validity and reliability. RESULTS: The European Heart Failure Self-Care
      Behaviour Scale is a 12-item, self-administered questionnaire that covers items
      concerning self-care behaviour of patients with heart failure. Face-validity and
      concurrent validity was established and the internal consistency of the scale was
      tested using pooled data of 442 patients from two centres in Sweden, three in the
      Netherlands and one in Italy. Cronbachs's alpha was 0.81. CONCLUSION: The
      instrument is a valid, reliable and practical scale to measure the self-reported
      self-care behaviour of heart failure patients. It is ready to use by
      investigators evaluating the outcome of heart failure management programmes that
      target changes in patients' self-care practices.

PMID- 12798837
TI  - Uptake of self-management strategies in a heart failure management programme.
AB  - BACKGROUND: Multidisciplinary heart failure programs including patient education
      and self-management strategies such as daily recording of body weight and use of
      a patient diary decrease hospital readmissions and improve quality of life.
      However, the degree of uptake of individual components of these programs and
      their contribution to patient benefit are uncertain. METHODS: Patients with heart
      failure admitted to Auckland Hospital were randomised into the management or
      usual care groups of the Auckland heart failure management study (AHFMS).
      Patients in the management group were given a heart failure diary for the
      recording of daily weights, attended a heart failure clinic and were encouraged
      to attend three education sessions. Patients in the usual care group received
      routine clinical care, mainly from general practitioners. Patients were followed
      to 12 months. This study investigated the uptake of self-management by assessing
      diary use and self-weighing behaviour in the group receiving the heart failure
      intervention, and compared the level of knowledge of heart failure self
      management of the management group to the control group after 12 months. RESULTS:
      Of the 197 patients in the AHFMS, 100 patients were included in the management
      group and received a diary and education about heart failure self-management
      including monitoring weight daily. Of these patients, 76 patients used the diary.
      These patients were on more medication; were more likely to attend the education
      sessions, heart failure clinic, and primary care, and had a lower mortality rate
      over the course of the study. Variables independently associated with use of the
      diary included less severe symptoms (OR 15, 95% confidence intervals 1.7, 144),
      frequent attendance at the heart failure clinic (OR 15, 95% CI 3, 78) and
      attendance at an education session (OR 8, 95% CI 1.5, 42). Of the 76 patients who
      used the diary, 51 weighed themselves regularly. More of these patients owned
      scales at home; they were also more likely to attend the education sessions, and
      experienced fewer hospital admissions than those patients who did not weigh
      themselves regularly. Variables independently associated with regular self
      weighing included the presence of scales at home (OR 6.3, 95% CI 1.7, 14.1), left
      ventricular ejection fraction >30% (OR 4.3, 95% CI 1.1, 17.5), and attendance at
      the education session(s) (OR 6.3, 95% CI 1.7, 14.1). Patients in the management
      group exhibited higher levels of knowledge at 12 months of follow-up and were
      more likely to monitor their condition using daily weighing, compared to the
      control group. CONCLUSIONS: At 12 months of follow-up, implementation of self
      management strategies including daily weight monitoring and level of education on
      self-management was significantly higher in the management group than the control
      group. For the patients in the management group, not using the diary or inability
      to perform daily weighing were associated with less frequent attendance at the
      heart failure clinic and education sessions and poorer health outcomes. In this
      study, attendance at the education sessions was associated with the adoption of
      self-management, underlining the importance of education in multidisciplinary
      heart failure programmes. Self-weighing could be increased by provision of scales
      to all patients. The subset of patients who did not adopt self-management
      strategies in this study were at high risk of death or readmission.

PMID- 12798838
TI  - Is multidisciplinary care of heart failure cost-beneficial when combined with
      optimal medical care?
AB  - BACKGROUND: Multidisciplinary care (MDC) of heart failure (HF) can significantly
      reduce rates of unplanned hospitalisation, the major cost component of HF care.
      AIMS: This prospective, randomised, controlled study examines the cost-benefits
      of MDC of HF in the setting of optimal medical care. METHODS: 98 NYHA class IV HF
      patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine
      care (RC; n=47) of HF. A direct intervention cost was calculated from contact
      time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation
      costs for HF were calculated at a daily rate of 242. Outcomes were determined in
      monetary terms, i.e. the cost of the service per hospitalisation prevented and
      net costs/savings at 3 months. RESULTS: The direct intervention cost of the MDC
      team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3
      months, there were a total of 12 unplanned HF readmissions in the RC group (25.5%
      rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number
      needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The
      cost of the service per hospitalisation prevented was 586. The intervention
      produced a net cost saving of 37,216 for 51 patients treated over 3 months.
      Sensitivity analyses using 50% variation in costs and lower relative risk
      reductions confirmed the cost-benefits of the intervention. CONCLUSION: MDC of HF
      remains cost-beneficial when combined with optimal, medical care. The significant
      clinical and cost-benefits suggest that this intensive approach to MDC and
      medical management should become the standard of care for HF.

PMID- 12798839
TI  - Update of clinical trials from the American College of Cardiology 2003. EPHESUS,
      SPORTIF-III, ASCOT, COMPANION, UK-PACE and T-wave alternans.
AB  - The American College of Cardiology provided much useful new information to inform
      those who care for patients with heart failure about what they should and should
      not adopt into current clinical practice. The EPHESUS trial suggests a much wider
      role for aldosterone antagonists for the management of heart failure and left
      ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer,
      simpler warfarin substitute soon. ASCOT reinforces the potential futility of
      statin therapy unless it is well targeted. The results of the COMPANION study
      investigating cardiac resynchronisation devices and implantable defibrillators
      were encouraging but inconclusive and/or hard to interpret. UK-PACE again
      questions the use of dual chamber pacing. T-wave alternans is an interesting
      experimental technique that may be useful in selecting which patients need an
      implantable defibrillator, although the technology needs testing in an
      appropriate patient population.

PMID- 12798840
TI  - Depression and congestive heart failure: are antidepressants underutilized?

PMID- 12798841
TI  - [Plasticity of adult stem cells].
AB  - Until recently, adults stem cells, defined by their self-renewal and
      differentiation abilities, were thought to be tissue-specific. This concept has
      been challenged by bone marrow transplantation experiments in mice, demonstrating
      generation of cells of different phenotype after transplantation of marrow or
      muscle cells. The term "plasticity" has been coined to explain this phenomenon
      which could be due to the persistence in adult tissues, of stem cells with
      multidifferentiation ability or to the "transdifferentiation" ability of some
      adult cells committed to differentiation, under the influence of unknown
      environmental cues. The relationship of the cells at the origin of the stem cells
      plasticity with a new type of mesodermal cell designed under the term of
      "multipotent adult progenitor cell" (MAPC) remains to be determined. The
      discovery of this latter is a major advance in this field as the MAPC have
      isolated from the adult bone marrow and presents certain characteristics of
      embryonic stem cells with the demonstration of their totipotency towards many
      tissues, including hematopoiesis. The discovery of the adult stem cell plasticity
      phenomenon in general, represents a major change in our concepts of stem and
      developmental biology and possibly the basis for the development of future cell
      therapy protocols.

PMID- 12798842
TI  - [Natural killer lymphocyte activation in response to stress].
AB  - Function of T and natural killer (NK) lymphocytes is tightly controlled by the
      balance of activating and inhibitory signals. NK receptors belong to different
      families: KIRs ("Killer cell Immunoglobulin-like Receptor") and ILTs
      ("Immunoglobulin-like Transcript"), mainly inhibitory which binds to HLA class I
      alleles; C-type lectin NK receptors such as CD94/NKG2A which is inhibitory and
      binds to HLA-E; NCR ("Natural Cytotoxicity Receptors") which directly activate NK
      cells. These include molecules NKp30, NKp44, NKp46 et NKG2D. Cellular stress
      (viral and bacterial infections, tumours) may modulate NK function by different
      mechanisms: decrease in HLA class I molecules expression resulting in the lack of
      engagement of the inhibitory receptors and ultimately NK cell activation;
      modulation of CD94/NKG2A inhibitory function through expression of peptides
      presented by HLA-E as for instance from heat shock proteins; NK activation
      through NCR expression. Among these, NKG2D is an activating receptor expressed by
      NK cells and subsets of alphabeta and gammadelta and T cells. Major NKG2D ligands
      in humans are MIC ("MHC class I related") molecules which are stress-inducible
      during a viral (CMV) or bacterial infection (M. tuberculosis, E. coli). They may
      also be expressed by tumors. Therefore, they could play a role in activating NK
      and/or T lymphocyte responses in these conditions.

PMID- 12798843
TI  - [Prions and risks for blood transfusion: the situation in 2003].
AB  - In 2003, Prions still constitute a biological enigma and a public health concern.
      The risks of transmission of the so called "mad cow disease" are now under
      control but concerns still persist about potential secondary transmissions,
      notably via blood transfusion. Information obtained from diseases previously
      observed in animals (scrapie of sheep and goat) and in man (Kuru, Creutzfeldt
      Jakob disease) demonstrate the complexity of the relations between these
      transmissible agents and their host. The difficulty in decontamination, the very
      long silent incubation period during which diagnosis is not possible and the lack
      of treatment are alarming elements which explain the increased perception of risk
      for these diseases. The development of rapid screening tests used on bovine at
      slaughterhouse has represented an important improvement in the development of a
      targeted protection against these agents. Today, technical evolutions in
      diagnosis let us imagine the possibility of blood detection for prions: on one
      hand new garanties for security may arise but on the other hand it points out the
      potential infectivity of blood with these agents responsible for constant fatal
      diseases. Precautionary security measures have to ensure an optimal ratio
      benefit/risk for the patient and thus, in this field, to balance the risk linked
      to prions with those clearly identified elsewhere.

PMID- 12798844
TI  - [European Union and blood transfusion].
AB  - Blood transfusion is progressing, Europe is growing, European blood transfusion
      organisations are developing rapidly. The first step was the publication of a new
      directive (2002/98/CE). The directive is the result of a compromise between
      technocracy, lobbying and blood transfusion professionals. European blood
      transfusion must be based on medical, scientific and social criteria. Two
      imperatives must be considered: the respect of ethics and; independence from the
      commercial system. The primary objective is to give satisfaction to patients
      while respecting blood donors.

PMID- 12798845
TI  - [State and perspectives of the French haemovigilance system. Presentation of the
      data collected over 9 years].

PMID- 12798846
TI  - [The number of cell separators existing in France in 2003].
AB  - The "2002 Apheresis" Group was commissioned by the President of the Etablissement
      francais du sang to carry out a study on the national stock of automated
      apheresis devices and think about a method to harmonize techniques. The objective
      was twofold: to facilitate the initiation of public procurement procedures as
      well as to streamline the stock and to match practices. The members of the "2002
      Apheresis" group first carried out an inquiry based on a nationwide
      questionnaire. They analyzed and compared the performances of the various
      separators. They also consulted suppliers on their short-term (2 years) projects.
      They finally met all regional apheresis correspondents. The group was then able
      to make suggestions to organize this activity as a part of a national apheresis
      scheme. Lastly, they helped devising public procurement procedures for the coming
      two years. This group is going to obtain a long-term recognition with the
      creation of a "Collection Group" conducted by the Scientific and Medical
      directors board at the Etablissement francais du sang.

PMID- 12798847
TI  - [How human sciences can help to understand blood donation?].
AB  - In France, the necessity of managing sanitary risks associated with blood
      transfusion has induced a strong medicalization of blood collection. Practicing
      this activity of transfusion medicine confronts the professional with problems
      which the medical science is not sufficient to answer: curbs and motivations for
      donating, seasonal and geographic fluctuations in blood collection, sense of pre
      donation interview, individual or collective contestings of guidelines for blood
      collection. From recent sociological works on donation in France, especially on
      blood donation, this paper suggests reporting the complexity of blood donation
      thought process and the necessity to refer to human and social sciences to
      approach it in a best way. Understanding the gift should help professionals to
      communicate not only on the promotion of blood donation, but also on the risk and
      its management.

PMID- 12798848
TI  - [Transfusional perspectives for ex vivo control of hematopoiesis].
AB  - Our increasing knowledge of the mechanisms of blood regulation allows us to
      envisage the production of cells in quantities sufficient enough to have
      transfusional interest. We present the state of the art on our capacity to
      amplify hematopoietic stem cells (HSC) and to force their differentiation into
      the erythroid lineage. We describe the difficulties met ex vivo for
      simultaneously reaching a very high level of expansion to have meaningful
      transfusional interests and obtaining a complete terminal maturation up to
      enucleation. We describe here a procedure for massively amplifying HSC from human
      cord blood to produce erythroblastic precursors able to differentiate in vivo
      into mature red cells after infusion. Although we do not suggest to replace
      classical blood transfusion, we consider that this approach may become
      complementary.

PMID- 12798849
TI  - Immunogenomics of hematopoietic stem cell transplantation.
AB  - Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) incur the
      risk of graft-versus-host disease (GVHD) even when the donor is a sibling who
      shares the major histocompatibility antigens. Therefore, even the perfect HLA
      match does not represent the optimal genetic match between donors and recipients
      in HSCT. In addition to the HLA complex other genetic systems operate and affect
      the outcome of HSCT. These include minor histocompatibility systems (inducing
      bona fide allogeneic responses) as well as a series of functional polymorphisms
      in cytokines and chemokines and receptors genes. Among the items affecting the
      outcome of HSCT the incidence and severity of infections have an important
      impact. Polymorphisms of genes controlling both arms of the immune responses to
      pathogens (innate vs. cognate) are strong candidates for susceptibility factors
      to infection in allogeneic transplantation. These include the MHC alleles (HLA
      class I, class II, MIC) CD1, Toll and TLR genes MBP, MPO genes.). In addition to
      the NK alloreactivity induced by HLA class I epitopes mismatching (a common
      situation in HSCT) variations in the genotype of the KIR genes may also be
      encountered between the donor and the recipient leading to potentially harmful or
      beneficial combinations. An integrated knowledge of the role and hierarchy of the
      most important genetic factors (MHC and non-MHC) will provide the rationale for a
      comprehensive matching in HSCT. This short review provides a panorama of this
      strategic issue for further development of HSCT.

PMID- 12798850
TI  - [Peri-operative use of EPO].
AB  - In moderately anaemic patients, Autologous Blood Donation is much less effective
      than Erythropoietin (EPO) at constituting a pre-operative RBC reserve. Indeed,
      the ability to give blood is limited or even impossible for anaemic individuals.
      EPO lowers the risks associated with autologous and allogeneic transfusions,
      while improving probably the quality of life of the patients. EPO therapy is
      efficient, in moderate anaemic patients, to reduce allogeneic transfusion when
      iron supplementation is associated. All blood conservation techniques carry their
      own efficiency limits, constraints and risks that, in addition to institutional
      considerations and individual patient characteristics, are determinant to settle
      a blood conservation strategy. But to optimise benefit/cost/effectiveness of this
      technique, it is important to take into account the delay before surgery, the
      anticipated blood loss for the procedure that varies among institutions and the
      tolerable blood loss without transfusion for the patient. To reduce the cost, a
      strategy according to baseline haematocrit and to blood loss has to be adapted at
      each patient. Furthermore, when the delay between the first EPO injection and the
      surgical procedure is sufficient, the number of injections can be easily reduced
      to obtain the same Ht the day prior to surgery.

PMID- 12798852
TI  - [Allogeneic adoptive immunotherapy].
AB  - Recognition of the importance of immune cells present in a hematopoietic graft
      has resulted in a significant change in the perception of allogeneic
      hematopoietic transplantation. Such a transplant modality is now perceived has a
      very efficient form of adoptive allogeneic immunotherapy unfortunately associated
      with significant toxicity.

PMID- 12798851
TI  - Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory
      diseases.
AB  - Therapeutic polyclonal intravenous immunoglobulin (IVIg) consists of normal IgG
      obtained from the pools of plasma of several thousand healthy blood donors. IVIg
      is used as substitutive treatment of primary and secondary immunodeficiences.
      Since the first study of Paul Imbach who demonstrated the beneficial effect in
      idiopathic thrombocytopenic purpura, IVIg is also used in a number of autoimmune
      and inflammatory diseases. The immunoregulatory effects of IVIg in autoimmune
      diseases depend on the interaction of Fc portion of immunoglobulins with Fc
      receptors and on the selection of lymphocyte repertoires of patients through
      variable regions of infused immunoglobulins. IVIg modulates the activation and
      effector functions of B and T lymphocytes, neutralizes pathogenic autoantibodies,
      interferes with antigen presentation and has a strong anti-inflammatory effect
      which depends on its interaction with the complement system, cytokines and
      endothelial cells. The immunomodulatory potential of IVIg in patients is thus a
      result of a variety of complex mechanisms that act in a synergy.

PMID- 12798853
TI  - [Molecular genotyping: development and limits].
AB  - Kits dedicated to molecular genotyping are now commercially available and are
      routinely used for diagnosis purpose. In the future these kits that use the
      classical reverse dot-blot approach will be replaced by micro-arrays, DNA chips
      and Labs on a chip. Some systems and DNA chips designed for medical diagnosis are
      already available. The present main problem is their very high cost.

PMID- 12798854
TI  - [Therapeutic indications of intravenous immunoglobulins].
AB  - Intravenous Immunoglobulin (IVIg) provide a wide spectrum of antibody
      specificities in patients with antibody deficiencies and restore immune
      homeostasis in patients with auto-immune diseases. Controlled trials have now
      been performed in a large number of diseases: in primary and secondary antibody
      deficiencies, auto-immune neurological diseases and various other auto-immune or
      systemic inflammatory conditions. Mechanisms of action of IVIg are multiple and
      often associated for a given disease. These mechanisms are however incompletely
      understood and therapeutic effect of IVIg remains to be investigated in a wide
      range of diseases.

PMID- 12798855
TI  - [Immunohematologic characteristics in the Afro-caribbean population. Consequences
      for transfusion safety].
AB  - Polymorphism encountered within the immunogenic blood group antigens is
      responsible for allo-immunization after transfusion or pregnancy. Antigen
      frequency differs depending on the ethnic background. This is the case for the
      Afro-caribbean population. Three levels of differences can be identified: common
      antigens in the RH, FY, JK and MNS blood groups, high frequency antigens in the
      RH, KEL, FY and MNS blood groups and low frequency antigens in the RH and KEL
      blood groups. When donors are primarily European caucasian in ancestry, the
      ethnic polymorphism may affect donor service in term of supply and demand. The
      effects of differences in antigen frequency are especially important when long
      term transfusion support is needed such as in sickle cell disease. When a Black
      patient is immunized against an association of common antigens for the Caucasian
      population (ex: anti-RH2, anti-FY1, anti-JK2, anti-MNS3) or against a high
      frequency antigen always present in the Caucasian population (anti-MNS5), only
      rare blood from the same ethnic population kept frozen at the rare blood bank can
      be transfused to avoid immuno-haemolytic accidents.

PMID- 12798856
TI  - [Transfusion-transmitted bacterial infection: residual risk and perspectives of
      prevention].
AB  - Bacterial contamination of blood components represents today the highest
      infectious risk of blood transfusion, the risk is particularly high when it
      affects platelet concentrates. The residual risk of transfusion reaction due to
      bacterial contamination of platelets concentrates remains stable. For all
      severity 1 case occurs with 25,000 distributed platelets concentrates and 1 death
      occurs with 200,000 distributed units. In France, efforts have focused on the
      prevention of contamination during donation--involving measures such as rejecting
      the first few millilitres of donated blood and improving skin disinfection--and
      the prevention of bacterial proliferation in platelets concentrates--notably by
      removing leukocytes and ensuring high-quality storage of donated blood. Improving
      strategies for reducing the risks of bacterial contamination is one of the
      priorities of the French National Blood Transfusion Service (l'Etablissement
      francais du sang-EFS). There is currently considerable debate about the relative
      importance of bacterial screening methods and methods for inactivating pathogens
      present in PC. Automated culture (Biomerieux) and the ScanSystem (Hemosystem) and
      BDS (Pall) method are the most advanced detection systems available, to our
      knowledge. In term of pathogen inactivation system for platelets, Intercept
      (Baxter) is nearing the commercial market. These new prevention have logistic
      and/or functional consequences that will require close scrutiny methods. A
      national study group is currently considering the consequences of each of these
      methods and should give its opinion at the end of the first half of 2003.

PMID- 12798857
TI  - [Critical analysis of the new ministerial order about guidelines in
      immunohaematology].
AB  - The evolution of the methods used in immunohematology is a constant concern for
      all those involved in the process. Thus, during the last few years, new
      technologies have been introduced which aim at improving performance. This
      improvement is not limited to the search for an overall increase in specificity
      sensibility; it also takes into account the capability to detect "the clinical
      significant" as well as the limitations of human reliability, which justifies the
      introduction of automation and computerization. The whole of these methodological
      evolutions associated with that of the performance of re-agents, legitimate to
      modify the law about the realization of erythrocyte typing and detection of
      irregular antibodies. In order to ensure the immunohematologic safety of
      transfusions, it was also necessary to place the entire transfusion process under
      computer control: patient identification, sample collection, test results and
      release of blood.

PMID- 12798858
TI  - [Hematopoietic stem cells].

PMID- 12798859
TI  - [The major histocompatibility complex as self-referential].
AB  - In order to effectively perceive the huge diversity of antigenic determinants to
      which it is confronted, the immune system uses referring internal images from
      self. The major histocompatibility complex constitutes the main reference to
      self, essential to the operating system of T and NK lymphocytes. It is involved
      in shaping the T operating repertoire in the thymus, where each differentiating
      thymocyte, with its TCR interacting with the MHC-peptide self complexes exposed
      by thymic presenting cells, should answer to both questions: Is it really
      necessary (positive selection) Is not dangerous (negative selection)? Once in
      periphery, naive T lymphocytes will undergo an homeostatic control helping their
      survival through the same contacts between TCR and MHC-peptide self complex than
      those which allowed the thymic positive selection. In a more hypothetic way, it
      is possible that contact between a T lymphocyte and the rare foreign MHC-peptide
      complexes spread at the surface of antigen presenting cell, is not sufficient to
      initiate its activation. Some arguments exist to involve the MHC-peptide self
      complexes themselves in the activation process.Finally, the MHC also constitutes
      a quality referential for the NK lymphocytes. When a somatic cell, infected by a
      virus or transformed, repress the expression of one or more of its class I HLA
      alleles, this absence of the self is perceived by the NK lymphocytes which
      proceed to its elimination through cytolysis. This disposition to sanction the
      non-self is also used for therapeutic purpose in the case of a non HLA identical
      allogenic hematopoietic stem cells graft.

PMID- 12798860
TI  - [Proteome and transcriptome].

PMID- 12798861
TI  - [Application of molecular biology to blood transfusion safety: the nucleic acid
      testing].
AB  - Nucleic Acid Testing (NAT) for HIV-1 and HCV has been introduced in France and
      became mandatory for all homologous blood donations since July 1st 2001 in
      addition to serology screening. Previously, a feasibility study led to the
      selection of 2 technologies : a TMA based assay (Chiron) uses the Procleix HIV
      /HCV assay on pools of 8 samples and a PCR based assay from BioMerieux-Roche
      which is a combination of an RNA extraction system (NucliSens, BioMerieux) with a
      fully automated system for nucleic acid amplification and detection (Cobas
      Amplicor, Roche). This system uses the Cobas Ampliscreen HCV test v.2.0 and the
      The Cobas Ampliscreen HIV test v1.5, on 24 sample pools. Pooling was required
      because single-donation testing is not yet feasible, as a result of the
      limitations in automation available for all current NAT technologies. The two
      technologies were easily implemented and showed nearly the same detection limit
      for HCV RNA and HIV-1 RNA. During a one-year period, from July 1st 2001 to June
      30, 2002, out of the 2.5 million donations tested, the NAT yield resulted in one
      HIV-1 RNA positive-antibody negative donation and one HCV RNA positive-antibody
      negative donation. Two HIV NAT positive-antibody negative donations were missed
      by minipool NAT because a very low viral load. Moreover, the NAT implementation
      did not impact on blood component availability, including platelet concentrates.

PMID- 12798862
TI  - [Clinical selection of blood donors].
AB  - For 20 years, the organization set up to insure the blood transfusion safety has
      never stopped strengthening. It is based on clinical and epidemiological
      selection of the blood donation candidates, biologic selection of blood donations
      and different physico-chemical techniques for pathogens reduction or inactivation
      in blood products. In France, this organization is optimized by the assertion of
      the voluntary and non-remunerated character of blood donation registered in the
      law of January 4th, 1993. The blood donors selection is structured in three
      successive stages. The first stage is the pre-donation information. The second
      stage begins with reading and filling out an info-questionnaire which prepare for
      an interview with a physician. This interview is specially directed to prevention
      of transfusion-transmitted infections and the prevention of adverse reactions
      after a 400 to 600 mL collection of whole blood or components. Finally, the third
      stage is the delivery of a post-donation information which invites the donor to
      contact the "etablissement francais du sang" (EFS) in case of a new event arisen
      after the donation or in case of reviewing of its own answers during the medical
      interview.

PMID- 12798863
TI  - [Electronic data interchange between Healthcare Establishments and French Blood
      Establishment].

PMID- 12798864
TI  - [Non conventional transmissible agents and emerging viruses].
AB  - Most infections occurring after blood transfusion or tissue engraftment come from
      a contamination of bacterial origin. Apart from these cases, most contaminating
      infectious pathogens are of known origin and detected for the blood donation
      qualification. In certain cases, there is the possibility of blood transmission
      of unknown infectious pathogens; sometimes, such pathogen is not unknown but very
      uncommon or unlikely. Consequences of blood transmission of such pathogens are
      different according to the pathogen itself and to the immune status of the
      recipient. This leads to the principle of precaution. The present manuscript aims
      at discussing these aspects.

PMID- 12798865
TI  - [Guidelines in clinical immunohematology].
AB  - In order to take into account the improvement of the knowledge, technologies,
      automation and computerization in immuno-haematology, the French national
      regulatory service have redefined the way to complete immunohaematology tests and
      their links to the blood component distribution. We describe these modalities for
      each test considering three questions "What?", "When?" and "How?".

PMID- 12798866
TI  - [Technical difficulties in clinical immunohaematology].

PMID- 12798867
TI  - [Follow-up of the feto-maternal allo-immunization].
AB  - Immunohaematological tests used in antenatal patients have come a long way.
      However, despite a great deal of progress, we should not loose sight of the fact
      that these tests give only an indirect measurement and will only help the
      obstetrician, in conjunction with other fetal parameters, to assess the severity
      of the haemolytic disease (HD) of the fetus and newborn. The best method to
      assess the severity is the direct determination of foetal blood group hemoglobin
      after foetal blood sampling but this procedure is not without risk. Since 10
      years ago, it is possible to determine the RHD genotype of the fetus using
      amniocytes and, today, maternal plasma directly. All pregnant women should be
      grouped for ABO-RH-KEL1 and the sera tested for clinically irregular antibodies
      (anti-RH are still the most frequent). The trend in anti-RH levels is more
      important than the level itself. The perfect technique for anti-RH quantitation
      has not been developed. Manual titration is simple but only provides rough,
      semiquantitatives estimates of anti-RH concentration. Quantitative
      haemagglutination methods, using auto-analyzers and appropriate anti-RH1
      standards, measure in microg/ml, are sensitive, rapid and have acceptable intra
      laboratory reproductibility.

PMID- 12798868
TI  - [The research and development policy of the French blood establishment].

PMID- 12798869
TI  - Postmortem parenthood and the need for a protocol with posthumous sperm
      procurement.
AB  - OBJECTIVE: Posthumous sperm procurement involves harvesting gametes from a
      recently deceased man for cryopreservation and future use in ART. This paper
      discusses the practical and ethical role of posthumous sperm procurement in
      medical practice and society and submits possible solutions, including the
      establishment of formal policies and protocols. DESIGN: English-language
      literature review and bioethical discussion. RESULT(S): In the United States, an
      increase in requests and protocols has been documented. International requests
      and regulation are variable. CONCLUSION(S): Posthumous sperm procurement is
      fraught with ethical dilemmas, including informed consent, privacy, inheritance,
      and child welfare. To establish appropriate medical practice, it is important to
      consider all stakeholders in the decision-making process. We believe that an
      acceptable and ethical resolution can be obtained only through the collaborative
      input of all involved parties. We have looked to U.S. and international sources
      for guidance in current practice and to gain insight into the formulation of
      future policies.

PMID- 12798870
TI  - Do assisted reproductive technologies cause adverse fetal outcomes?

PMID- 12798871
TI  - Immunopathogenesis of chlamydia trachomatis infections in women.
AB  - OBJECTIVE: To develop a model of pathogenesis by which Chlamydia trachomatis
      progresses from acute to chronic infection, and finally serious disease
      (salpingitis, tubal occlusion). DESIGN: Review of current literature located
      through web-based Medline searches using key words: Chlamydia trachomatis,
      immunology, cytokines, heat shock protein, infertility. RESULT(S): Cell-mediated
      immune mechanisms appear to be critical in determining whether acute infection is
      resolved or progresses into chronicity with pathological outcome. What determines
      the particular immune pathway depends on a range of determinants-HLA subtype and
      human genetics, cytokine profile, infectious load, route of infection, and
      endocrinology. A clearer picture of the natural history of chlamydial pathology
      may assist in providing better predictors of those women who may go on to develop
      significant sequelae after infection. CONCLUSION(S): Predicting those who may
      develop serious disease, including infertility, may contribute to improved
      management of such persons during earlier stages of infection and assist in
      prevention.

PMID- 12798872
TI  - Oxidative stress may be a piece in the endometriosis puzzle.
AB  - OBJECTIVE: To assess the total antioxidant potential of women with endometriosis
      associated infertility, women with idiopathic infertility, and fertile controls.
      DESIGN: Retrospective study. SETTING: University medical hospital. PATIENT(S):
      Sixty-five women admitted for diagnostic laparoscopy. MAIN OUTCOME MEASURES:
      Peritoneal fluid samples were analyzed for superoxide dismutase activity and
      total antioxidant status on spectrophotometry, glutathione peroxidase activity on
      enzyme-linked immunosorbent assay, and lipid peroxides levels on colorimetry.
      RESULT(S): Mean activity of superoxide dismutase, glutathione peroxidase, and
      total antioxidant status was lowest and lipid peroxide level was highest among
      infertile patients with endometriosis. Women with idiopathic infertility, in
      contrast, had the highest superoxide dismutase, glutathione peroxidase, and total
      antioxidant status activity and the lowest lipid peroxide level. CONCLUSION(S):
      High antioxidant potential is not a contributing factor in women with idiopathic
      infertility. Low total antioxidant status and low activity of antioxidant enzymes
      in the peritoneal fluid of infertile women with endometriosis probably do not
      influence fertility in these women, but these factors may play a role in the
      development of the disease.

PMID- 12798873
TI  - Poor response after hormonal stimulation for in vitro fertilization is not
      related to ovarian aging.
AB  - OBJECTIVE: To investigate whether the diminished efficacy of ART in young poor
      responders compared to young normal responders is due to a quantitative or a
      qualitative oocyte factor. DESIGN: Retrospective comparative analysis. SETTING:
      University-based infertility center. PATIENT(S): Nine thousand six hundred forty
      four patients who underwent ART procedures at our hospital from 1993 until 2001.
      INTERVENTION(S): Controlled ovarian hyperstimulation, ultrasonographic monitoring
      of the ovarian response, oocyte retrieval, ART procedure, embryo transfer, and
      follow-up of pregnant patients until 12 weeks of amenorrhea. MAIN OUTCOME
      MEASURES: Clinical rates of pregnancy and miscarriage. RESULT(S): Nine thousand
      six hundred forty-four ART cycles were analyzed. The pregnancy rate for poor
      responders was significantly lower than for normal responders (17% vs. 35%). In
      cycles in which two good-quality embryos were transferred, the pregnancy rate was
      similar in poor responders and normal responders (33% vs. 42%). The rate of
      miscarriage was no higher in poor responders than normal responders.
      CONCLUSION(S): Young poor responders have a lower pregnancy rate than young
      normal responders because they have fewer oocytes, which leads to fewer good
      quality embryos to choose from for transfer. The quality of their oocytes and
      embryos is not inferior to that of normal responders.

PMID- 12798874
TI  - Improved implantation rate after chemical removal of the zona pellucida.
AB  - OBJECTIVE: To evaluate the implantation rate achieved after chemical removal of
      the zona pellucida from day 5 human in vitro-derived embryos. DESIGN:
      Prospective, randomized, controlled study. SETTING: A tertiary care infertility
      clinic. PATIENT(S): Two hundred fifty-seven patients undergoing IVF with transfer
      of morulas or blastocysts on day 5 after oocyte retrieval. All patients had had
      at least two previous implantation failures. INTERVENTION(S): Chemical removal of
      zona pellucida by using acidic Tyrode's solution vs. no removal (controls). MAIN
      OUTCOME MEASURES: Clinical pregnancy rate and implantation rate per transfer.
      RESULT(S): Embryos without zona pellucida implanted at nearly twice the rate of
      control embryos (15.7% vs. 27.5%). The pregnancy rate was also significantly
      higher in the zona pellucida-free group than the control group (31.0% vs. 46.1%).
      Removal of zona pellucida was most effective in embryos with delayed development,
      which reached the morula or early cavitating stage on day 5 of in vitro culture
      (implantation rate, 12.1% vs. 25.7%). CONCLUSION(S): Chemical removal of zona
      pellucida from day 5 in vitro cultured human embryos is an effective and safe
      method of significantly improving the implantation rate, especially of embryos
      with delayed development.

PMID- 12798875
TI  - Chromosomal information derived from single blastomeres isolated from cleavage
      stage embryos and cultured in vitro.
AB  - OBJECTIVE: To evaluate the potential of proliferation of single blastomeres
      isolated from human cleavage-stage embryos for use in preimplantation genetic
      diagnosis of chromosomal abnormalities. DESIGN: A laboratory study of chromosomal
      content of blastomeres isolated from embryos of patients from an in vitro
      fertilization program. SETTING: University hospital laboratory. PATIENT(S):
      Couples undergoing IVF or ICSI. INTERVENTION(S): Blastomeres were isolated from
      normally fertilized cleavage-stage human embryos, cultured in vitro or fixed
      immediately, and analyzed by fluorescence in situ hybridization (FISH) probes.
      MAIN OUTCOME MEASURES: Chromosomal information yielded by blastomeres cultured in
      vitro compared with those obtained from blastomeres that were processed for
      chromosomal analysis directly after isolation. RESULT(S): The percentage of
      cultured blastomeres that produced FISH results was significantly lower than the
      percentage of blastomeres processed for FISH directly after isolation (72% vs.
      90%). Lack of FISH results from cultured cells, which in most cases was related
      to nuclear anomalies, was significantly more frequent among nondivided than
      divided blastomeres (39% vs. 21%). Both cultured and noncultured cells showed
      diploid, aneuploid and polyploid chromosome complements on FISH. Compared with
      directly processed cells, cultured cells yielded a higher proportion of polyploid
      patterns (22.9% vs. 6.1%). Of the cultured blastomeres that divided, 18% produced
      progeny with mosaicism. CONCLUSION(S): Although blastomere culture may increase
      the number of cells available for chromosomal analysis, the high frequency of
      nuclear defects and the occurrence of polyploidy and mosaicism among cultured
      cells discourage the use of blastomere isolation and proliferation strategy for
      use in preimplantation genetic diagnosis.

PMID- 12798876
TI  - Psychological characteristics and factors related to willingness to donate again
      among anonymous oocyte donors.
AB  - OBJECTIVE: To assess post-donation psychological status of a large sample of
      professionally recruited, paid anonymous donors and to determine whether there
      were any differences between those who were willing to donate again and those who
      were not. DESIGN: Cross-sectional survey. SETTING: Healthy donors who were
      recruited by two private groups. SUBJECT(S): One hundred fifteen donors who had
      completed at least one donation cycle at one of six IVF programs in a large
      Midwestern city. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Self-report
      questionnaire assessing psychological symptoms, self-esteem, expectations,
      satisfaction, and attitudes toward donation. RESULT(S): Psychological
      symptomatology and self-esteem were in the normal range. Altruism and
      compensation were the two most frequently cited motivators for donation. Of the
      donors, 82% were moderately to very satisfied with the donation experience. First
      time donors were significantly younger, reported more post-donation psychiatric
      symptoms, and had slightly lower self-esteem. Of the donors, 35% stated they
      would donate again; 37% would not, and 28% were undecided. Donors who were
      willing to donate again reported significantly less ambivalence about donation
      and significantly greater satisfaction with the medical aspects of donation.
      CONCLUSION(S): Approximately one third of donors are willing to donate more than
      once. These women report less ambivalence and greater satisfaction with the
      donation experience.

PMID- 12798877
TI  - Local injury to the endometrium doubles the incidence of successful pregnancies
      in patients undergoing in vitro fertilization.
AB  - OBJECTIVE: Exploration of the possibility that local injury of the endometrium
      increases the incidence of implantation. DESIGN: Prospective study. SETTING:
      Clinical IVF unit. PATIENT(S): A group of 134 patients, defined as good
      responders to hormonal stimulation, who failed to conceive during one or more
      cycles of IVF and embryo transfer (ET). INTERVENTION(S): The IVF treatment and ET
      were preceded by repeated endometrial biopsies, in a randomly selected 45 of a
      total of 134 patients. MAIN OUTCOME MEASURES: Outcome of IVF-ET treatments.
      RESULT(S): Transfer of a similar number of embryos (3.4 +/- 1.0 and 3.1 +/- 0.9
      in the experimental and control patients, respectively) resulted in rates of
      implantation (27.7% vs. 14.2%, P =.00011), clinical pregnancy (66.7% vs. 30.3%, P
      =.00009), and live births per ET (48.9% vs. 22.5%, P =.016) that were more than
      twofold higher in the experimental group as compared to controls. CONCLUSION(S):
      These results suggest that IVF treatment that is preceded by endometrial biopsy
      doubles the chance for a take-home baby.

PMID- 12798878
TI  - Live births after vitrification of oocytes in a stimulated in vitro fertilization
      embryo transfer program.
AB  - OBJECTIVE: To assess the usefulness of the vitrification method in clinical
      practice. DESIGN: Clinical study of vitrification of human oocytes. SETTING: A
      university-affiliated hospital. PATIENT(S): Thirty-four patients who agreed to
      undergo additional IVF-ET after the failed fresh cycle using the previously
      vitrified/thawed oocytes. INTERVENTION(S): Surplus oocytes from the IVF-ET
      patients were vitrified for the next cycle. MAIN OUTCOME MEASURES: Morphologic
      normality of post-thawed oocytes, fertilization, cleavage, pregnancy, and
      implantation rate. RESULT(S): Overall morphological survival and fertilization
      rates of vitrified/liquefied oocytes were 68.6% (325/474) and 71.7% (142/198),
      respectively. Pregnancy rate and implantation rate per embryo transfer were 21.4%
      (6/28) and 6.4% (8/125), respectively. All pregnancies resulted in the delivery
      of healthy babies (1 twin and 5 singletons/6 pregnancies). CONCLUSION(S): The
      feasibility of the vitrification method for human oocytes was confirmed by our
      clinical results. Subsequent studies on vitrification and thawing procedures
      should be undertaken for further optimizing the vitrification method.

PMID- 12798879
TI  - The androgenic sex hormone profile is an essential feature of metabolic syndrome
      in premenopausal women: a controlled community-based study.
AB  - OBJECTIVE: To evaluate sex hormones in premenopausal white women with metabolic
      syndrome (MBS). DESIGN: Cross-sectional controlled community-based study.
      SETTING: Pieksamaki District Health Center, Pieksamaki, Finland. PATIENT(S): Five
      hundred forty-three women, aged 34 to 54 years, were screened according to
      National Cholesterol Education Program criteria: waist >88 cm, hypertension
      >/=130/>/=85 mm Hg, hypertriglyceridemia >/=1.7 mmol/L, high-density lipoprotein
      (HDL)-cholesterol <1.3 mmol/L, and fasting glucose >/=6.1 mmol/L. Sixty-three
      women fulfilled at least three of the above-mentioned criteria and were enrolled.
      Eighty-eight age-matched women without MBS served as controls. INTERVENTION(S):
      None. MAIN OUTCOME MEASURES: Sex steroid levels in relation to insulin
      sensitivity and body composition. RESULT(S): A markedly lower insulin sensitivity
      index and higher free androgen index were detected in the women with MBS than in
      the controls. Abdominal obesity and increased diastolic blood pressure were
      significantly associated with high free androgen index in multiple regression
      analysis. CONCLUSION(S): A hyperandrogenic hormone profile appeared to be a
      typical feature of premenopausal female MBS even without polycystic ovary
      syndrome (PCOS).

PMID- 12798880
TI  - Central abdominal fat and endogenous hormones during the menopausal transition.
AB  - OBJECTIVE: To investigate the effect of endogenous hormone levels on central
      abdominal fat during the menopausal transition in a population-based cohort of
      Australian-born women. DESIGN: Prospective observational study. SETTING:
      Population-based sample. Body composition was assessed in the Royal Melbourne
      Hospital, and interviews were conducted at the patient's home. SUBJECT(S): One
      hundred two women from the Melbourne Women's Midlife Health Project. Data,
      physical measures, and blood were obtained by interview when the longitudinal
      study commenced (baseline) and at the time of the total body scan approximately 5
      years later. Body composition was measured using dual-energy X-ray
      absorptiometry. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Total body fat and
      central abdominal fat. RESULT(S): The 102 women were either premenopausal or in
      the early menopausal transition at baseline. At the time of their dual-energy X
      ray absorptiometry scan, 31 were in the early menopausal transition, 22 were in
      the late menopausal transition, and 49 were postmenopausal. Multiple regression
      analysis found that total percentage of body fat was associated with weight
      measures, whereas central abdominal fat was also positively associated with
      baseline free T index (FTI) and with the increase in FTI since baseline.
      CONCLUSION(S): The major hormonal change associated with central adiposity during
      the menopausal transition is the increase in the FTI. This effect is significant
      even after allowing for baseline and final weight.

PMID- 12798881
TI  - Comparative effects of oral esterified estrogens with and without
      methyltestosterone on endocrine profiles and dimensions of sexual function in
      postmenopausal women with hypoactive sexual desire.
AB  - OBJECTIVE: In some women, a decline in sexual interest accompanies a relative
      androgen insufficiency after menopause. We sought to characterize the hormonal
      effects of the combination of oral esterified estrogens and methyltestosterone
      and to investigate whether this regimen improves hypoactive sexual desire.
      DESIGN: Double-blind randomized trial. SETTING: Healthy volunteers in a
      multicenter research environment. PATIENT(S): Postmenopausal women taking
      estrogen therapy who were experiencing hypoactive sexual desire. INTERVENTION(S):
      4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the
      combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone
      (n = 107). MAIN OUTCOME MEASURES: Baseline and end-of-study measurements of total
      and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean
      change in level of sexual interest or desire as rated on the Sexual Interest
      Questionnaire. RESULT(S): Treatment with the combination of esterified estrogens
      and methyltestosterone significantly increased the concentration of bioavailable
      testosterone and suppressed SHBG. Scores measuring sexual interest or desire and
      frequency of desire increased from baseline with combination treatment and were
      significantly greater than those achieved with esterified estrogens alone.
      Treatment with the combination was well tolerated. CONCLUSION(S): Increased
      circulating levels of unbound testosterone and suppression of SHBG provide a
      plausible hormonal explanation for the significantly improved sexual functioning
      in women receiving the combination of esterified estrogen and methyltestosterone.

PMID- 12798882
TI  - Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase
      gene are associated with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether genetic variability in the gene encoding
      microsomal epoxide hydrolase (EPHX) contributes to individual differences in
      susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN:
      Retrospective case-control study. SETTING: University-based clinic. PATIENT(S):
      One hundred twelve white women with PCOS and 115 healthy controls.
      INTERVENTION(S): None. MAIN OUTCOME MEASURES: The presence of two single
      nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G
      (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to
      pair of loci haplotype analysis to examine the estimated haplotype frequencies of
      the two SNPs, of unknown phase, in the PCOS and control groups. Estimated
      haplotype frequencies were assessed using the maximum-likelihood method, using an
      expectation-maximization algorithm. RESULT(S): Single point allele and genotype
      distributions in exon 3 and exon 4 of the EPHX gene were not statistically
      different between the groups. However, according to the haplotype estimation
      analysis, we observed a significantly elevated frequency of haplotype C-G (His113
      Arg139) in the PCOS group versus the control group. The odds ratio for PCOS
      associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95%
      confidence interval 1.1-4.8). CONCLUSION(S): The use of two intragenic single
      nucleotide polymorphisms jointly in haplotype analysis of association
      demonstrated that the genetically determined low activity haplotype C-G (His113
      Arg139) was significantly associated with PCOS.

PMID- 12798883
TI  - Relation of intra-abdominal fat distribution to metabolic disorders in nonobese
      patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the relation between intra-abdominal fat distribution
      and metabolic disorders in nonobese patients with the polycystic ovary syndrome
      (PCOS). DESIGN: Prospective case-control study. SETTING: University-based
      hospital. PATIENT(S): Thirty nonobese patients with PCOS and 30 lean women with
      regular menstrual cycles (controls). All participants had a body mass index <
      25kg/m(2). MAIN OUTCOME MEASURES: Subcutaneous and intra-abdominal visceral and
      preperitoneal fat thicknesses were assessed by ultrasonography. Glucose tolerance
      and insulin sensitivity were evaluated by standard 75-g oral glucose tolerance
      test and area-under-the-curve analysis. Serum hormones and lipid profile were
      measured. RESULT(S): The mean preperitoneal and visceral fat thicknesses were
      significantly greater in nonobese patients with PCOS. Subcutaneous fat mass was
      similar between the PCOS and control groups. Nonobese patients with PCOS had
      glucose intolerance, hyperinsulinemia, and dyslipidemia, manifested by high serum
      levels of triglyceride, total cholesterol, and high-density lipoprotein (HDL)
      levels and low serum low-density lipoprotein (LDL) levels. No correlation existed
      between subcutaneous fat thickness and the metabolic variables in nonobese
      patients with PCOS. However, serum triglyceride levels correlated with visceral
      fat and preperitoneal fat thickness. The mean HDL level correlated negatively
      with visceral fat and preperitoneal fat thickness. The area under the curve for
      insulin and mean fasting insulin levels correlated positively with visceral fat
      thickness. In multiple regression analysis, visceral fat thickness contributed
      significantly to high serum triglyceride and fasting insulin levels.
      CONCLUSION(S): Intra-abdominal preperitoneal and visceral fat accumulation may
      contribute to the development of glucose and lipid metabolism disorders in
      nonobese patients with PCOS.

PMID- 12798884
TI  - Correlations between concentrations of interleukin-12 and interleukin-13 and
      lymphocyte subsets in the follicular fluid of women with and without polycystic
      ovary syndrome.
AB  - OBJECTIVE: To investigate a possible correlation between interleukin-12 (IL-12)
      and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients
      with and without polycystic ovarian syndrome (PCOS). DESIGN: Controlled clinical
      study. SETTING: University hospital. PATIENT(S): Seventy-eight infertile women
      undergoing IVF-embryo transfer. INTERVENTION(S): The subjects underwent blood
      sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES: Follicular
      fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T
      helper, and T-suppressor lymphocytes. RESULT(S): The level of IL-12 detected in
      follicular fluid (FF) was significantly lower in patients with PCOS than in
      normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL,
      respectively); in contrast, FF IL-13 concentrations were significantly higher in
      the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7
      pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated
      T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was
      observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A
      levels. No significant differences were observed when these data were compared
      with embryological parameters. CONCLUSION(S): The present study shows significant
      differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte
      numbers in the subset of patients with PCOS as compared to normally ovulating
      women.

PMID- 12798885
TI  - Relationship among maternal serum endocrinology, placental karyotype, and
      intervillous circulation in early pregnancy failure.
AB  - OBJECTIVE: To evaluate the relationship among maternal serum endocrinology,
      placental karyotype, and intervillous blood flow in missed miscarriage. DESIGN:
      Cross-sectional study of maternal serum, transvaginal ultrasound/Doppler, and
      placental cytogenetic and immunohistochemical investigations. SETTING: Tertiary
      care academic hospital. PATIENT(S): One hundred fifty-two women with missed
      miscarriage between 7 and 13 weeks of gestation. INTERVENTION(S): Ultrasound
      features, placental intervillous circulation findings on color Doppler imaging,
      and maternal serum level of alpha-fetoprotein (AFP), beta-hCG, E(2), P, and
      inhibin A were compared retrospectively with placenta karyotype and hCG
      immunochemistry. MAIN OUTCOME MEASURES: Data were analyzed according to karyotype
      results, presence or absence of an intervillous circulation, and delay between
      fetal demise and evacuation. RESULT(S): The presence of intervillous blood flow
      and serum concentrations of the different hormones were independent of placental
      karyotype. Serum beta-hCG and P were significantly higher in cases with
      intervillous blood flow. No difference in immunostaining for beta-hCG was found
      between placental tissues from normal pregnancies and missed miscarriages, but
      significantly higher villous beta-hCG content was found on Western blotting in
      miscarriage with a recent fetal demise. CONCLUSION(S): The excessive entry of
      maternal blood inside the placenta in the early stage of most miscarriages is
      unrelated to conceptus karyotype, and hCG features may reflect a temporary
      attempt of the trophoblast to stabilize after the initial oxidative insult.

PMID- 12798887
TI  - Gonadotropin-releasing hormone agonist treatment before abdominal myomectomy: a
      controlled trial.
AB  - OBJECTIVE: To ascertain whether adjuvant gonadotropin-releasing hormone (GnRH)
      agonist therapy decreases blood loss during abdominal myomectomy. DESIGN:
      Randomized controlled trial. SETTING: Academic reproductive surgery center.
      PATIENT(S): One hundred premenopausal women requiring first-line conservative
      surgery for symptomatic intramural or subserous fibroids. INTERVENTION(S): Eight
      weeks of treatment with depot triptorelin before myomectomy or immediate surgery.
      MAIN OUTCOME MEASURES: Intraoperative blood loss, operating time, degree of
      difficulty of the procedure, and short-term rate of fibroid recurrence.
      RESULT(S): Mean (+/-SD) intraoperative blood loss was 265 +/- 181 mL in
      triptorelin recipients and 296 +/- 204 in patients who had immediate surgery
      (mean difference, -31 mL [95% CI, -108 to 46 mL]). No significant differences
      were observed in blood loss according to uterine volume, number of fibroids
      removed, or total length of myometrial incisions. Most procedures in either group
      were of routine difficulty. On ultrasonography 6 months after myomectomy, four
      women in the GnRH agonist group and one in the immediate surgery group had tumor
      recurrence. CONCLUSION(S): Treatment with a GnRH agonist before abdominal
      myomectomy has no significant effect on intraoperative blood loss. Thus,
      systematic use of medical therapy before abdominal myomectomy does not seem to be
      justified.

PMID- 12798886
TI  - A randomized, placebo-controlled, dose-ranging trial comparing fulvestrant with
      goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy.
AB  - OBJECTIVE: To compare the use of a new antiestrogen fulvestrant with goserelin in
      reducing uterine fibroid growth before hysterectomy. DESIGN: An international,
      multicenter, randomized, placebo-controlled study. SETTING: Departments of
      obstetrics and gynecology. PATIENT(S): Premenopausal women (n = 307) diagnosed
      with uterine fibroids requiring hysterectomy. INTERVENTION(S): Over a 12-week
      period, patients received fulvestrant (50 mg, 125 mg, or 250 mg) as an i.m.
      injection, goserelin (3.6 mg) as a s.c. injection, or an injection-matched
      placebo once every 4 weeks. Patients underwent a hysterectomy at week 13. MAIN
      OUTCOME MEASURES: Efficacy endpoints included changes in fibroid growth,
      endometrial thickness, and uterine volume. The excretion of urinary markers of
      bone resorption was also examined. RESULT(S): Goserelin significantly reduced
      fibroid growth and endometrial thickness compared with placebos. Fulvestrant did
      not significantly alter fibroid volume or endometrial thickness or change
      endpoints such as endometrial histology or vaginal bleeding. Fulvestrant was
      associated with fewer postmenopause-related adverse events than goserelin.
      Goserelin, but not fulvestrant, significantly increased markers of bone
      resorption. CONCLUSION(S): At doses equivalent to those used for the treatment of
      breast cancer in postmenopausal women, fulvestrant did not significantly inhibit
      fibroid growth and, of particular note, did not lead to bone resorption.

PMID- 12798888
TI  - Calcium requirements for human sperm function in vitro.
AB  - OBJECTIVE: To determine extracellular calcium (Ca(2+)) requirements for the
      maintenance of human sperm function in vitro. DESIGN: Prospective study. SETTING:
      Basic research laboratory. PATIENT(S): Normozoospermic volunteers provided fresh
      semen samples; follicular fluid (human FF) and oocytes were collected from women
      undergoing IVF-ET. INTERVENTION(S): Spermatozoa were incubated for </=18 hours in
      media containing different CaCl(2) concentrations (maximum, 2.5 mM [control]).
      MAIN OUTCOME MEASURES: Protein tyrosine phosphorylation patterns, development of
      hyperactivated motility, induction of the acrosome reaction (AR) in response to
      human FF, and sperm interaction with homologous zona pellucida (ZP). RESULT(S):
      Cells maintained for 18 hours in medium containing >/=0.1 mM of Ca(2+) were able
      to undergo the AR when exposed to human FF in the presence of 2.5 mM of Ca(2+).
      Calcium concentrations of >/=0.22 mM were sufficient to reach protein tyrosine
      phosphorylation levels and hyperactivated motility values similar to those of
      controls. Higher Ca(2+) concentrations (>/=0.58 mM) were required to produce
      maximum human FF-induced AR in previously capacitated cells and to obtain an
      adequate sperm-ZP binding. CONCLUSION(S): Different steps of the fertilization
      process have distinctive Ca(2+) requirements. Whereas 0.22 mM of Ca(2+) is
      sufficient for the development of some capacitation-related events, human FF
      induced AR and sperm-ZP interaction require 0.58 mM of this cation.

PMID- 12798889
TI  - Cyclooxygenase-2 is expressed in human fibroblasts isolated from intraperitoneal
      adhesions but not from normal peritoneal tissues.
AB  - OBJECTIVE: To determine whether the COX-2 gene is expressed in human fibroblasts
      isolated from normal peritoneal and adhesion tissues. DESIGN: Prospective
      experimental study. SETTING: University medical center. PATIENT(S): Five patients
      undergoing laparotomy for pelvic pain. Primary cultures of fibroblasts were taken
      from both peritoneum and adhesion tissues. INTERVENTION(S): Hypoxia treatment of
      the primary cultured fibroblasts. MAIN OUTCOME MEASURES: We used the multiplex
      reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry
      techniques to determine whether COX-2 mRNA and its protein were present in normal
      peritoneal and adhesion fibroblasts from the same patients. Total RNA was
      extracted from cultured fibroblasts and subjected to multiplex RT-PCR to detect
      the presence of COX-2 mRNA in these cells. Cultured fibroblasts from all tissues
      were also fixed on slides and stained with COX-2 monoclonal antibody labeled with
      immunofluorescence. RESULT(S): COX-2 mRNA and its protein were absent in normal
      peritoneal fibroblasts from all five subjects but were present in adhesion
      fibroblasts from the same patients, as indicated by the multiplex RT-PCR and
      immunohistochemistry techniques. Hypoxia treatment significantly induced the mRNA
      and COX-2 protein levels in normal peritoneal fibroblasts to levels seen in
      adhesion fibroblasts under normoxic conditions. However, hypoxia had no effects
      on COX-2 expression by adhesion fibroblasts. CONCLUSION(S): Adhesion fibroblasts
      develop a specific phenotype, an adhesion phenotype, which is in part
      characterized by the expression of COX-2. The expression of COX-2 mRNA in
      adhesion fibroblasts and the induction of COX-2 in peritoneal fibroblasts in
      response to hypoxia indicate a possible inflammatory response. Regulation of COX
      2 may alter peritoneal healing and may provide the opportunity to reduce
      postoperative adhesion development.

PMID- 12798890
TI  - Effect of raloxifene, 17beta-estradiol, and progesterone on mRNA for vascular
      endothelial growth factor isoforms 121 and 165 and thrombospondin-1 in Ishikawa
      cells.
AB  - OBJECTIVE: To compare the mRNA expression of vascular endothelial growth factor
      (VEGF) 121 and 165 isoforms and thrombospondin-1 (TSP-1) after raloxifene, 17beta
      E(2), and P administration in cultured Ishikawa cells. DESIGN: Prospective basic
      research study. SETTING: Jones Institute for Reproductive Medicine, Eastern
      Virginia Medical School, Norfolk, Virginia. PATIENT(S): None. INTERVENTION(S):
      Ishikawa cells were cultured in vitro. Raloxifene, 17beta-E(2), and P at
      concentrations of 0.01, 0.1, and 1.0 microM were added to confluent cells. MAIN
      OUTCOME MEASURES: The VEGF 121 and 165 isoforms and TSP-1 mRNA expression from
      treated Ishikawa cells were analyzed by reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULT(S): 17beta-Estradiol increased both VEGF 121 and 165
      mRNA compared to control. Raloxifene did not increase either VEGF 121 or 165 mRNA
      above control values. Progesterone at all concentrations did not increase VEGF
      121 isoform mRNA, whereas VEGF 165 isoform was minimally increased by P at the
      lowest concentration. Progesterone and raloxifene increased TSP-1 mRNA
      expression. 17beta-Estradiol did not stimulate TSP-1 mRNA expression at any
      concentration. CONCLUSION(S): Raloxifene did not stimulate VEGF 121 and 165,
      whereas it increased TSP-1 mRNA synthesis in Ishikawa cells. Our hypothesis is
      that raloxifene's lack of endometrial stimulation may be partly mediated by an
      antiangiogenic effect.

PMID- 12798891
TI  - The transfer point is a novel measure of embryo placement.
AB  - OBJECTIVE: To study the relationship between IVF-ET pregnancy outcomes and
      measures of embryo placement. DESIGN: Case-control study. SETTING: Tertiary care
      center. PATIENT(S): Twenty-three patients who underwent two ultrasonography
      guided ETs, of which one resulted in a clinical pregnancy and the other did not.
      MAIN OUTCOME MEASURES: Point of embryo placement normalized to the endometrial
      cavity length (the transfer point), distance from the point of embryo placement
      to the uterine fundus, time required for ET, contact with the uterine fundus, and
      evidence of trauma. Videotaped ETs were quantitatively analyzed. RESULT(S): From
      February 1, 2000, to March 31, 2001, videotaped ETs from 23 pairs of pregnant and
      nonpregnant cycles were identified. Embryo placement was more shallow in
      pregnancy cycles than in nonpregnancy cycles. The groups did not differ in the
      absolute distance of embryo placement to the fundus, ovarian stimulation, or
      other features of the ET. CONCLUSION(S): The transfer point may serve as a better
      marker of embryo position than does the absolute distance to the uterine fundus.

PMID- 12798892
TI  - Suppression of pelvic pain during hysteroscopy with a transcutaneous electrical
      nerve stimulation device.
AB  - OBJECTIVE: To evaluate the effectiveness of transcutaneous electrical nerve
      stimulation (TENS) as a pain control method during office hysteroscopy. DESIGN: A
      prospective, randomized study. SETTING: Centre for Minimally Invasive Surgery,
      Department of Gynecological Science and Perinatology, "La Sapienza" University,
      Rome, Italy. PATIENT(S): One hundred forty-two patients undergoing office
      hysteroscopy. INTERVENTION(S): Application of a TENS device on the patient's
      abdomen before and during office hysteroscopy. MAIN OUTCOME MEASURES: The level
      of pain experienced by the patients was assessed using a 10 cm visual analog
      scale; the side effects and changes in the hemodynamic parameters were evaluated.
      RESULT(S): The patients treated with TENS during hysteroscopy (group A, n = 71)
      were compared with a control group (group B, n = 71) on whom the TENS device was
      not used. The women in the TENS group experienced a significantly lower level of
      pain during hysteroscopy. No differences in side effects were observed between
      both group. CONCLUSION(S): TENS is a simple, efficient, and safe method of
      relieve pain during office hysteroscopy.

PMID- 12798893
TI  - Successful freezing and thawing of blastocysts cultured in sequential media using
      a modified method.
AB  - OBJECTIVE: To evaluate the clinical role of blastocyst freezing and thawing after
      prolonged culturing in sequential media. DESIGN: Retrospective analysis of 293
      blastocyst freeze-thawing cycles. SETTING: University hospital infertility unit.
      PATIENT(S): Nonselected couples undergoing IVF. INTERVENTION(S): Blastocysts were
      frozen and thawed by a modified method. MAIN OUTCOME MEASURES: Blastocyst
      recovery after freeze-thawing and pregnancy rates after the transfer. Evaluation
      of the effect of the number of transferred blastocysts, the method of IVF, and of
      the woman's age on the results achieved by frozen-thawed blastocysts. RESULT(S):
      Frozen-thawed blastocysts provided a 29.5% clinical pregnancy rate per transfer.
      After the transfer of three blastocysts the pregnancy rate was 42.0%, and after
      the transfer of one or two blastocysts it was approximately the same (25.0% and
      28.0%, respectively). The method of IVF did not affect pregnancy rates, but the
      increasing age of the woman did. Pregnancies were characterized by a low abortion
      rate (8.0%) regardless of the age of the woman. CONCLUSION(S): A modified method
      for blastocyst freeze-thawing provides good clinical results. It offers the
      possibility for a single-thawed blastocyst transfer and represents a good
      alternative for older women because of its lower risk of spontaneous abortion.

PMID- 12798894
TI  - Hyaluronic acid can successfully replace albumin as the sole macromolecule in a
      human embryo transfer medium.
AB  - OBJECTIVE: To examine the effect on pregnancy and implantation rates when highly
      purified, fermentation-based hyaluronic acid was the only macromolecule
      supplement to the transfer medium in a human IVF program. DESIGN: Prospective
      randomized study. SETTING: In vitro fertilization center in an academic medical
      institution. PATIENT(S): Eighty patients were included in this prospective
      randomized double blind study. Inclusion criteria were age </=35 years, the
      availability of at least three embryos eligible for transfer on day 3 after
      fertilization, and no more than three previous embryo transfer attempts.
      INTERVENTION(S): All embryos were cultured in P1 medium containing 10% synthetic
      serum substitute (SSS) until day 3. Patients were randomly allocated to two
      groups; in treatment group A (40 patients), embryos were transferred to P1 medium
      supplemented with 0.5 mg/mL hyaluronic acid for 5-10 min before their
      intrauterine transfer. In the control group B (40 patients), embryos were
      transferred, as routinely performed, in P1 medium containing 10% SSS. MAIN
      OUTCOME MEASURES: Clinical pregnancy and implantation rates. RESULT(S): The mean
      age of the female partner was 28.7 +/- 3.3 years and 29.7 +/- 3.8 years for
      groups A and B, respectively. In group A, 103 embryos were transferred and in
      group B, 97 embryos were transferred for a similar mean number of 2.6 +/- 0.6 and
      2.4 +/- 0.5 embryos/transfer, respectively. Twenty-five pregnancies were achieved
      in group A, and 21 pregnancies in group B. This led to a comparable clinical
      pregnancy and implantation rates of 62.5% and 34% as compared to 52% and 26.8%
      for groups A and B, respectively. CONCLUSION(S): Hyaluronic acid can successfully
      replace albumin as a sole macromolecule in a human embryo transfer medium and
      result in high pregnancy and implantation rates. The use of this supplement is an
      important step in the development of human embryo culture media free of blood
      derived additives.

PMID- 12798895
TI  - Intraoperative injection of prostaglandin F2alpha in a patient undergoing
      hysteroscopic myomectomy.
AB  - OBJECTIVE: To present a case of one-step total hysteroscopic myomectomy using
      prostaglandin F(2alpha). DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 38-year-old woman with a sessile submucous leiomyoma.
      INTERVENTION(S): Hysteroresectoscopy using an intraoperative injection of
      prostaglandin F(2alpha) under laparoscopic monitoring. MAIN OUTCOME MEASURES:
      Endoscopic appearance, clinical symptoms, and imaging diagnosis. RESULT(S): After
      resection of the protruding portion of the myoma, injection of prostaglandin
      F(2alpha) was used to cause the remnant to project into the uterine cavity,
      allowing complete removal. CONCLUSION(S): Intraoperative use of prostaglandin
      F(2alpha) may allow one-step hysteroresectoscopy of a sessile submucous
      leiomyoma.

PMID- 12798896
TI  - Pelvic pain, low blood pressure, and hemolysis after outpatient hysteroscopy in a
      patient with glucose-6-phosphate dehydrogenase deficiency.
AB  - OBJECTIVE: To report hemolytic crisis in a woman with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency who underwent diagnostic hysteroscopy using
      endoscopic instruments sterilized in gluteraldehyde and phenol disinfectant.
      DESIGN: Case report. SETTING: Surgical unit of a university hospital. PATIENT(S):
      A 53 year-old woman with endometrial thickening on ultrasonography.
      INTERVENTION(S): Diagnostic hysteroscopy. MAIN OUTCOME MEASURES: Laboratory
      tests. RESULT(S): The patient experienced abdominal pain and acute hypotension 10
      minutes after diagnostic hysteroscopy. We attributed this event to the exposure
      of her genital mucosa caused by the hysteroscopic chemical disinfectant.
      CONCLUSION(S): Chemical sterilization of endoscopes can cause clinical
      manifestations in people with G6PD deficiency, a common enzyme abnormality. The
      phenol content in some chemical disinfectants for endoscopic instruments can also
      cause hemolytic crisis.

PMID- 12798897
TI  - Intrauterine reflux of media during cervical irrigation at embryo transfer.

PMID- 12798898
TI  - Sertoli cell and Leydig cell immunophenotypes in patients with or without AZF
      microdeletions.

PMID- 12798899
TI  - One triplet pregnancy in 510 controlled ovarian hyperstimulation and intrauterine
      insemination cycles.

PMID- 12798900
TI  - Submucous and outer myometrium leiomyomas are two distinct clinical entities.

PMID- 12798901
TI  - Effect of finasteride on the ovulatory function of normal women.

PMID- 12798902
TI  - Cryopreservation does not affect neovascularization of freely transplanted
      ovarian follicles.

PMID- 12798903
TI  - Impact of the gonadotropin-releasing hormone antagonist in oocyte donation
      cycles.

PMID- 12798904
TI  - Impact of xenoestrogens on the growth of human endometrial epithelial cells in a
      primary culture system.

PMID- 12798905
TI  - Vascular endothelial growth factor-mediator of PHSS?

PMID- 12798907
TI  - Vascular endothelial growth factor--mediator of OHSS?

PMID- 12798908
TI  - Life-table analysis falls short of the mark!

PMID- 12798909
TI  - Life-table analysis falls short of the mark!

PMID- 12798911
TI  - Smoking and sperm viability--a never-ending story.

PMID- 12798913
TI  - Suggestions on the use of LH.

PMID- 12798915
TI  - Does it all come down to postnatal aging of the primary oocyte?

PMID- 12798917
TI  - Stimulation protocols--floors and ceilings for LH activity.

PMID- 12798919
TI  - Stimulation protocols-floors and ceilings for LH activity.

PMID- 12798922
TI  - Concurrent infections with Trypanosoma brucei and Nippostrongylus brasiliensis in
      mice deficient in inducible nitric oxide.
AB  - Concurrent infection with Trypanosoma brucei (Tb) delays the normal protective
      responses of mice to the gastrointestinal parasite Nippostrongylus brasiliensis
      (Nb). The course of such infections was followed in mice genetically deficient in
      inducible nitric oxide synthase (INOS) to assess the role of nitric oxide (NO) in
      this effect. The time course of trypanosome infection in INOS deficient (INOS-/-)
      mice was similar to that in wild type (WT) and heterozygote (INOS+/-) mice but
      did not result in NO production. Although concurrent infection with Tb increased
      initial susceptibility to Nb in INOS-/- mice, the immune-mediated loss of N.
      brasiliensis and the associated decline in faecal egg output occurred more
      rapidly then in WT and INOS+/- littermates. Concurrent infection with
      trypanosomes markedly suppressed Concanavalin A (ConA)-induced in vitro
      proliferation of splenic lymphocytes in all groups, but had little effect on the
      responses of mesenteric node lymphocytes. Trypanosome infection was also
      associated with increased early release of interferon-gamma and reduced IL-5 from
      lymphocytes stimulated in vitro with ConA, but did not affect later release of IL
      5. The overall similarity of proliferative and cytokine responses in WT, INOS+/-
      and INOS-/- mice suggest that the suppressive effects of T. brucei on N.
      brasiliensis infection do not simply reflect depressed lymphocyte responsiveness
      or altered cytokine profiles. NO appears to be involved in suppression only of
      the later phases of the host responses to Nb.

PMID- 12798923
TI  - Sequence diversity in the amino-terminal region of the malaria-vaccine candidate
      serine repeat antigen in natural Plasmodium falciparum populations.
AB  - The amino-terminal region of the serine repeat antigen (SERA) of Plasmodium
      falciparum is a major malaria-vaccine candidate. Variation in this molecule is
      essentially dimorphic and alleles may be grouped into the types FCR3, K1 and
      Honduras1. The Honduras1-type is thought to be the product of homologous
      recombination between FCR3 and K1 alleles. Here we have examined patterns of
      sequence diversity in exon II of SERA gene, which encodes most of the amino
      terminal region of the antigen, in wild P. falciparum isolates from Indonesia
      (n=60), Myanmar (n=10) and Thailand (n=14). Among the Indonesian isolates the FCR
      3 type predominated (56/60), twenty of which we characterized as novel alleles. A
      new K1-type allele was also found. In Myanmar, however, all isolates displayed K1
      type SERA sequences, which included one new allele. The Honduras1-type was not
      detected in both countries. In contrast, the 14 isolates from Thailand displayed
      all three allelic types, with one new Honduras1-type and three new K1-type
      alleles. On examining the global distribution of SERA alleles by combining
      previously published sequence data with our results, the FCR3-type alleles
      predominated in Indonesia, Brazil, and Solomon Islands, but were not found in
      wild isolates from Myanmar and Africa. Brazil was the only area where K1-type
      alleles were not found. The distribution of Honduras1-type alleles seems to be
      mostly restricted to parasite populations from Vietnam, Thailand and Africa. In
      the allelic families FCR3 and K1, most diversity resulted from variation in
      sequence and number of octamer repeat units and of allotypes encoding the stretch
      of serine residues. Sequence analysis indicated that both insertions and
      deletions of repetitive motifs (creating variation within dimorphic allelic
      families) and homologous recombination between alleles belonging to different
      allelic families (creating Honduras1-type alleles) play a role in generating new
      SERA alleles. Since repeat motifs in the amino-terminal region of SERA contain
      epitopes recognized by parasite-inhibitory antibodies, sequence variation in exon
      II may represent one of the parasite's immune-evasion strategies.

PMID- 12798924
TI  - Acute outbreak of gnathostomiasis in a fishing community in Sinaloa, Mexico.
AB  - An increasing number of human cases of gnathostomiasis have been reported in
      Sinaloa, Mexico, most of whom have a custom of eating of raw fish dishes such as
      'cebiche'. Here we report five adult patients, three women and two men, having an
      acute episode of vomiting and abdominal pain a few minutes after eating a dish of
      cebiche prepared from a spotted sleeper perch (Eleotris picta) fished from a
      nearby lake in southern Sinaloa. All five patients experienced acute throat pain,
      chest and joint pains, headache and fever. One patient, a 55-year-old male, was
      hospitalized with suspected pancreatitis and pneumonia. By 8-9 days later, all
      five patients developed between three and 12 edematous, migrating skin lesions on
      the back, abdomen, upper and lower extremities, face, eye and scalp. By ELISA,
      all of them were sero-positive to Gnathostoma doloresi antigen and had elevated
      IgE levels. Eosinophilia was found in two patients. These patients lived in an
      agricultural and fishing community. In this community we carried out a sero
      epidemiological survey and study of living conditions in a random sample of 309
      individuals distributed in 74 households. Frequent consumption of raw fish was
      reported in 36% of households, and 12 individuals had a clinical history of
      migrating skin lesions. The sero-prevalence to Gnathostoma antigens was 34.95%.
      Five fish species and four species of ichthyophagous birds collected from three
      lakes in the village and a nearby estuary were infected with the advanced third
      stage larvae of G. binucleatum, a species found in Ecuador and Mexico. The
      results describe the first known outbreak of acute gnathostomiasis on the
      American continent.

PMID- 12798926
TI  - Experimental fascioliasis in the rat-like hamster, Tscherskia triton, and other
      rodent hosts.
AB  - Experimental infection with Fasciola hepatica and parthenogenetic Fasciola sp. in
      laboratory animals have been conducted in rats and rabbits. Inoculation of less
      than 5 metacercariae into rat-like hamsters, Tscherskia triton, is sufficient to
      establish Fasciola infections. The prepatent period of F. hepatica and the
      parthenogenetic Fasciola sp. in T. triton was shorter than that in rats and
      rabbits, suggesting that T. triton is a suitable experimental model for these
      flukes. In contrast, F. gigantica infection in T. triton did not yield adult
      flukes; T. triton, is therefore, considered to be an unsuitable host for F.
      gigantica. The cotton rat, Sigmodon hispidus, was an unsuitable host for the
      parthenogenetic Fasciola sp.

PMID- 12798925
TI  - Efficacy of administration of praziquantel on 2 days 2 weeks apart against
      Schistosoma japonicum eggs in mice.
AB  - We compared a group of mice given multiple oral doses of praziquantel (PZQ) on 1
      day 7 weeks after infection with Schistosoma japonicum and another group given
      multiple doses of PZQ over 2 days (7 and 9 weeks after infection) by examining
      the number of schistosome eggs and oograms in their tissues and feces. In the 1
      day-protocol group (4 x 100 mg/kg x 1 day), calcified dead eggs or shells
      accounted for 77.4 and 70.1% of the total EPG (the total number of immature eggs,
      mature eggs, and calcified eggs and shells per 1 g tissue) in the liver and small
      intestine, respectively, 11 weeks after infection. Shells accounted for nearly
      half of the total EPG (54.3% liver and 46.6% small intestine). Mature eggs
      accounted for 8.4% (liver) and 5.1% (small intestine) of the total EPG. Only
      shells were found in the feces. In the 2-day-protocol group (4 x 100 mg/kg x 2
      days, 2 weeks apart), dead eggs accounted for 87.2 and 89.5% of the total EPG in
      the liver and small intestine, respectively, 11 weeks after infection. Shells
      accounted for 62.5% (liver) and 75.8% (small intestine) of the total EPG. In the
      2-day group, mature eggs accounted for 0.9% (liver) and 0.6% (small intestine) of
      the total EPG. In liver and small intestine, the EPG of immature and mature eggs
      in the 2-day group was significantly smaller than in the 1-day group. Especially,
      the tendency was clear in the case of the EPG of mature eggs. There were no
      schistosome eggs in the feces of the 2-day group. We found that administration of
      PZQ over 2 days separated by a 2-week interval was effective against S.
      japonicum.

PMID- 12798927
TI  - The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei
      brucei in mice.
AB  - Consecutive administration of ascofuranone without glycerol was found to have
      therapeutic efficacy against Trypanosoma brucei brucei infection in mice. A
      suspension of ascofuranone (25-100 mg/kg) was administrated intraperitoneally
      every 24 h for 1-4 consecutive days to trypanosome-infected mice and efficacy was
      compared with oral treatment. With intraperitoneal administration, all mice
      treated with 100 mg/kg ascofuranone for 4 consecutive days were cured. On
      contrary, with oral treatment a higher dose of ascofuranone (400 mg/kg) was
      needed for 8 consecutive days to cure the mice. With intraperitoneal treatment,
      parasitemia was strongly suppressed, with almost all long slender bloodstream
      forms of the parasite changed to short stumpy forms by day 3 and the parasites
      have been eliminated 4 days after the start of treatment. These ascofuranone
      induced short stumpy forms were morphologically analogous to the stumpy forms 2
      days after peak parasitemia of pleomorphic clone of T. b. brucei GUTat 3.1.
      However, the properties of ubiquinol oxidase activity, which is the target of
      ascofuranone, in mitochondria isolated from before and after treatment, were
      almost same. The enzymatic activities of ubiquinol oxidase were only decreased to
      approximately 30% within a day after treatment, and then kept at nearly the same
      level. In the present study, we have improved regimen for administration of
      ascofuranone without glycerol, and demonstrated that consecutively administrated
      ascofuranone showed trypanocidal effects in T. b. brucei infected mice. Our
      present results strongly suggest that consecutive administration of ascofuranone
      may be an effective chemotherapy for African trypanosomiasis.

PMID- 12798928
TI  - Scuticociliata infection in the weedy sea dragon Phyllopteryx taeniolatus.
AB  - The weedy sea dragon Phyllopteryx taeniolatus at an aquarium in Kanagawa
      Prefecture were found infected by protozoan ciliate, 2001. The infected fish in
      particular, showed sloughing of the epidermis. Fish with intense infections
      showed sloughing of the dorsal fin, depigmentation of skin, anal distension and
      accumulation of ascitic fluid in the body cavity. In biopsies, ciliates were
      detected only in fresh mounts of abdominal dropsy and in the mucus on the body
      surface. Histopathological studies revealed ciliates mainly infected the dermis,
      and induced extensive detachment of the epidermis from the skin. Based on the
      arrangement and shape of the buccal structure and the number of somatic
      ciliature, ciliates isolated from the fishes belonged to the order
      Scuticociliatida. We discuss the major factors that bring about the death of
      weedy sea dragons.

PMID- 12798929
TI  - Induction of permeability changes and death of vertebrate cells is modulated by
      the virulence of Entamoeba spp. isolates.
AB  - Although Entamoeba histolytica is capable of inducing an apoptotic response in
      vertebrate cells in vitro (Cell. Microbiol. 2 (2000) 617), it is not known
      whether vertebrate cell death requires direct amoeba-vertebrate cell contact or
      simply the presence of amoebae in the area of the vertebrate cells. In addition,
      Entamoeba spp. vary in their virulence and pathogenicity. The potential effects
      of these critical parameters also have not been elucidated. We tested the
      virulent HM-1:IMSS isolate and the non-virulent Rahman isolate of E. histolytica,
      and the non-virulent E. dispar CYNO16:TPC isolate against two vertebrate cell
      lines, HeLa and Chinese hamster ovary cells in vitro using ethidium homodimer as
      a fluorescent indicator of changes in vertebrate cell permeability. Fluorescence
      appeared in vertebrate cell nuclei within approximately 2-3 min of contact
      between HM-1 amoebae and vertebrate cells independent of vertebrate cell type.
      However, vertebrate cells in the immediate vicinity of but not contacted by HM-1
      amoebae were not affected. In contrast, although both E. histolytica Rahman and
      E. dispar CYNO16 amoebae moved freely among and contacted vertebrate cells, the
      nuclei of the vertebrate cells never fluoresced implying that the cells remained
      alive and impermeant to the ethidium homodimer. This is the first demonstration
      that direct contact between virulent amoebae and vertebrate cells is required to
      kill vertebrate cells and that the process is restricted to virulent Entamoeba
      isolates. An understanding at the molecular level of the processes involved could
      help to reduce the pathology associated with this parasite.

PMID- 12798930
TI  - Use of a recombinant Clonorchis sinensis pore-forming peptide, clonorin, for
      serological diagnosis of clonorchiasis.
AB  - A recombinant pore-forming peptide of Clonorchis sinensis, clonorin, was
      evaluated for serodiagnostic reagent of clonorchiasis by enzyme-linked
      immunosorbent assay detecting IgG antibody. Recombinant clonorin showed 100%
      specificity and low sensitivity for sera of human clonorchiasis. In contrast, C.
      sinensis crude antigen revealed lower specificity and higher sensitivity than
      recombinant clonorin did. In sera of experimental rabbits, clonorin-specific IgG
      antibody was increased remarkably 8 weeks after the infection and retained around
      level of OD(490)=0.2 for 1 year. With excellent antigenic specificity, it is
      suggested that the recombinant clonorin can be used as an ingredient of the
      cocktail antigen for serodiagnosis of clonorchiasis from early stages of the
      infection.

PMID- 12798931
TI  - Anthelmintic efficacy of Flemingia vestita (Fabaceae): Effect of genistein on
      glycogen metabolism in the cestode, Raillietina echinobothrida.
AB  - The edible root-tuber peel of Flemingia vestita and its major active component,
      genistein, have been earlier shown to have a vermifugal/vermicidal effect on
      cestodes in vitro by causing a flaccid paralysis and alterations in the
      tegumental architecture and activity of several enzymes associated with the
      tegumental interface of the parasite. Pursuing further investigation on the mode
      of action of this putative anthelmintic, the crude peel extract and pure
      genistein were further tested in respect of glycogen metabolism in the fowl
      tapeworm, Raillietina echinobothrida. On exposure to the plant root peel crude
      extract (5 mg/ml) and genistein (0.2 mg/ml), the glycogen concentration was found
      to decrease by 15-44%, accompanied by an increase of activity of the active form
      of glycogen phosphorylase (GPase a) by 29-39% and decrease of activity of the
      active form of glycogen synthase (GSase a) by 36-59% in treated parasites as
      compared to untreated controls, but without affecting the total activity (a+b) of
      both the enzymes. Praziquantel (1 microg/ml), the reference drug, also caused
      quantitative reduction in glycogen level and alterations in enzyme activities
      somewhat at par with the genistein treatment. These results suggest that this
      plant-derived component may influence the glycogen metabolism of the parasite by
      directing it towards utilization of glycogen.

PMID- 12798932
TI  - Pyruvate kinase: current status of regulatory and functional properties.
AB  - Pyruvate kinase (PK) is a key enzyme for the glycolytic pathway and carbon
      metabolism in general. On the basis of the relevance and enormous diverse
      properties of this enzyme, this paper describes the results of a current and
      extensive review that determines the sites of conservation and/or difference in
      PK sequences, and the differences in the functional and regulatory properties of
      the enzymes. An alignment and analysis of 50 PK sequences from different sources
      and a phylogenetic tree are presented. This analysis was performed with reference
      to crystallographically characterized PK principally from E. coli, cat and rabbit
      muscle. A number of attributes of the enzyme that make it of particular interest
      in biomedicine and industry are also discussed.

PMID- 12798933
TI  - Genomic evidence for the absence of a functional cholesteryl ester transfer
      protein gene in mice and rats.
AB  - Mice and rats are naturally deficient in cholesteryl ester transfer protein
      (CETP) activity, although the reason behind the deficiency in activity is
      unknown. A search of mouse genome databases revealed sequences resembling 7 of
      the 16 human exons. However, these sequences could not code for a functional
      CETP. Analysis of the rat genome using Southern blotting revealed sequences
      complementary to human CETP cDNA, but RNase protection assays were unable to
      detect any Cetp gene expression in liver, adipose, or muscle. A search of rat
      whole-genome shotgun databases revealed exon-like sequences that would be unable
      to code for a functional CETP. An Ap3s1 pseudogene lay immediately upstream of
      the CETP-like sequences in mouse, but was nearly identical to the functional gene
      and unlikely to have been inserted prior to mouse-rat divergence. In contrast, a
      deletion leading to a nonsense codon was found in the exon 11-like sequences of
      both rat and mouse and not in any other species. Thus, the lack of CETP activity
      in both the mouse and the rat is most likely due to an evolutionary event that
      occurred before these species diverged and not to altered regulation of the gene
      or function of the gene product.

PMID- 12798934
TI  - Culture conditions affect induction of vitellogenin synthesis by estradiol-17
      beta in primary cultures of tilapia hepatocytes.
AB  - In vitro synthesis of vitellogenin (VTG), a female-specific protein, after
      estradiol-17 beta (E(2)) treatment was compared among different culture
      conditions using the hepatocytes of tilapia, Oreochromis mossambicus. VTG was
      measured by enzyme-linked immunosorbent assay. Comparison of Leibovitz's L-15
      medium (L-15), Williams' medium E (WE) and Medium 199 (M199), which have been
      used for hepatocyte cultures in certain teleost fishes, showed that monolayer
      formation of the hepatocytes on the plate in WE and M199 was faster than in L-15
      at the beginning of the culture. Morphological differences in the hepatocytes
      among the culture media were not evident by 96 h after culture. VTG synthesis in
      L-15 after E(2) treatment was higher than in WE and M199. A concentration of
      NaHCO(3) at 5 mM in L-15 resulted in faster monolayer formation of the cells and
      higher VTG synthesis than at 0 and 23 mM. Primary culture of the tilapia
      hepatocytes at 28 degrees C showed higher synthesis of VTG than at 23 and 33
      degrees C. These results suggest that nutritional requirements are vitally
      different among species, and there are optimal ranges in the pH and the
      temperature in cultured hepatocytes.

PMID- 12798935
TI  - In vitro effect of metal ions on the activity of two amphibian glyceraldehyde-3
      phosphate dehydrogenases: potential metal binding sites.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) was purified from
      two amphibian species, Xenopus laevis and Pleurodeles waltl. Comparative studies
      revealed that the two proteins differ by their subunit molecular masses, pI
      values and V8 digested peptide maps. The effect of zinc, cadmium and copper ions
      on GAPDH enzymatic activity has been examined in vitro. A time, metal
      concentration and metal type dependent inhibition was observed for both enzymes.
      X. laevis and P. waltl GAPDHs exhibit a much greater sensitivity to copper than
      to cadmium or zinc ions. Different half-lives and differential sensitivity to
      various metals was observed between the two enzymes with P. waltl GAPDH being
      remarkably tolerant to cadmium ions compared to the X. laevis enzyme. In order to
      understand the differential sensitivity of the two enzymes to metals, we produced
      3D models of both X. laevis and P. waltl GAPDH structures based upon known 3D
      structures of GAPDHs from other species. This necessitated, in a first step, to
      clone a 900 bp cDNA fragment encoding the nearly full-length P. waltl GAPDH.
      Spatial motif searches on the homology models indicated potential metal binding
      sites involving cysteine and histidine residues outside the catalytic sites,
      existing only in either the X. laevis or the P. waltl GAPDH sequences.

PMID- 12798936
TI  - Purification and characterization of perchloric acid soluble protein from rat
      lung.
AB  - We isolated a perchloric acid soluble protein from the post-mitochondria
      supernatant fraction of the rat lung and designated it as RLu-PSP1. The protein
      is soluble in 5% perchloric acid and was purified by ammonium sulfate
      fractionation and CM-Sephadex chromatography. The amino acid sequence of RLu-PSP
      was identical with that of rat liver PSP (RL-PSP). RLu-PSP inhibited protein
      synthesis in a rabbit reticulocyte lysate system. It was expressed mainly in
      cytoplasm of bronchioles and alveolar epithelial cells of the lung from 60-day
      old rats. In 15-day-old rat embryos, the epithelial-lining of the terminal buds
      of the respiratory tree was immunopositive. The expression of RLu-PSP increased
      from the embryonic 15th day to the postnatal 40th day. This is the first report
      on the presence of a PSP in rat lung and on its involvement in the regulation of
      cellular growth and differentiation.

PMID- 12798937
TI  - Cloning, sequencing and phylogenetic/phenetic classification of an estrogen
      receptor alpha (alpha) subtype of sheepshead minnow (Cyprinodon variegatus).
AB  - The estrogen receptor (ER) is a key component of the reproductive system of both
      teleosts and tetrapods. In this study, the sequence and evolutionary relationship
      of sheepshead minnow (Cyprinodon variegatus) ER were examined. Total RNA from
      livers of adult laboratory-reared gravid female C. variegatus was reverse
      transcribed to prepare cDNA. Nested pairs of gene-specific degenerative primers
      derived from conserved amino acid sequences of the ER DNA binding domain were
      used to amplify an internal fragment of the ER cDNA of C. variegatus using
      polymerase chain reaction (PCR) followed by rapid amplification of cDNA ends
      (RACE). The amplified cDNA products were inserted into pGEM T-Easy Vector for
      cloning and sequencing. The cloned ER cDNA segments gave a 524-amino-acid ER
      sequence, which represents approximately 80% of the sequence. The use of PHYLIP
      for phylogenetic analysis with the maximum parsimony method and for phenetic
      analysis with the neighbor-joining method, along with bootstrap resampling, using
      24 known sequences of alpha and beta ER subtypes (both teleosts and tetrapods)
      indicated that the ER cDNA sequence of C. variegatus has strong homology to the
      alpha-subtype (ER alpha) of other teleostean fish, especially the closely related
      killifish species, Japanese medaka (Oryzias latipes). Because ER alpha was the
      only subtype found, it appears that the alpha-subtype is predominant in C.
      variegatus liver.

PMID- 12798938
TI  - Cuticular hydrocarbons of the sunflower beetle, Zygogramma exclamationis.
AB  - Hydrocarbons were the major lipid class on the cuticular surface of adults,
      nymphs, and eggs of the sunflower beetle, Zygogramma exclamationis, characterized
      by gas chromatography-mass spectrometry. Minor amounts of wax ester from 40 to 48
      carbon atoms in size were only detected in larvae. The hydrocarbons ranged in
      size from 23 carbons (tricosene) to 56 carbons (trimethyltripentacontane) and
      were largely methylalkanes. The major components from females were 13,17,21
      trimethylnonatriacontane (19%) and from larvae was n-nonacosane (17%). Males had
      11,15- and 9,15-dimethylheptacosane (11%) and 13,17,21-trimethylnonatriacontane
      (11%) as the major components. In a sample of eggs, 13,17,21-nonatriacontane
      (16%) was the major component which was approximately 3 to 4-fold greater than
      the next most abundant hydrocarbons, dimethylheptacosanes, 2-methyloctacosane,
      methylnonacosanes, dimethyl- and trimethylheptatriacontanes and
      dimethylnonatriacontanes.

PMID- 12798939
TI  - Metabolism of intratesticular spermatozoa of a tropical teleost fish (Clarias
      gariepinus).
AB  - Sperm metabolism of a tropical fish species, the African catfish, Clarias
      gariepinus, was studied by measurements of sperm enzyme activity and metabolite
      levels. We also analysed the effect of metabolites, co-enzymes and enzymatic
      blockers on sperm motility behaviour and viability. Similar to other teleostean
      species, African catfish spermatozoa have the capacity for glycolysis,
      tricarboxylic acid cycle, oxidative phosphorylation, lipid catabolism, beta
      oxidation and osmoregulation. In immotile spermatozoa, lipid catabolism, beta
      oxidation, the tricarboxylic acid cycle and oxidative phosphorylation were
      important primary energy-delivering pathways; sperm oxygen consumption was 0.39
      0.85 microg O(2)/min/ ml of testicular semen. During motility, glycolysis, lipid
      catabolism and beta-oxidation of fatty acids occurred simultaneously, which is
      atypical for teleosts, and the spermatozoal respiration rate increased
      drastically by 15-25-fold. Also in contrast to other teleostean sperm cells, ATP
      levels remained stable during motility and immotile storage. The sperm cell
      status was unstable in the African catfish. Although the spermatozoa have
      osmoregulation ability, and even though balanced physiological saline solutions
      were used for sperm motility activation and sperm incubation, the motility and
      viability of spermatozoa quickly decreased at 28 degrees C, the spawning
      temperature of the African catfish. Cyclic AMP and inhibition of
      phosphodiesterase activity could not prolong sperm motility and viability. In
      contrast, at 6-10 degrees C motility was prolonged from approximately 30 s to >5
      min, probably due to decreased metabolic rates.

PMID- 12798940
TI  - Phospholipid fatty acids and sterols of two Cinachyrella sponges from the Saudi
      Arabian Red Sea: comparison with Cinachyrella species from other origins.
AB  - Phospholipid class compositions, fatty acids and sterols of the sponges
      Cinachyrella alloclada and C. kukenthali from the Saudi Arabian Red Sea were
      studied and compared with previous results for other Cinachyrella spp. collected
      in Senegal (East Atlantic) and New Caledonia (West Pacific). More than 50 fatty
      acids were identified as methyl esters and N-acyl pyrrolidides in each
      phospholipid mixture by GC/MS. Six fatty acids not hitherto found in nature were
      identified, namely 17-methyltetracosanoic in C. kukenthali and 18
      methyltetracosanoic, 18-methylpentacosanoic, 18-methylhexacosanoic, 18,24
      dimethyl-hexacosanoic and 6-bromo-5,9-nonacosadienoic acids in C. alloclada.
      Approximately 20 Delta 5,9 unsaturated fatty acids were found, including three 6
      brominated acids. The presence of bacteria was evidenced by the relatively high
      proportions of phosphatidylglycerol and high levels of branched short-chain fatty
      acids. A total of 20 free 3beta-hydroxysterols were found by GC/MS, including
      clerosterol in relatively high amounts and gorgosterol in low amounts. The latter
      sterol has not been reported to date in a sponge. Comparisons with Cinachyrella
      species from other geographical areas show marked differences for both
      phospholipid fatty acid and sterol compositions.

PMID- 12798942
TI  - Allantoin, the oxidation product of uric acid is present in chicken and turkey
      plasma.
AB  - Urate oxidase is not present in birds yet allantoin, a product of this enzyme,
      has been measured in birds. Studies were designed to compare the concentrations
      of plasma purine derivatives in chickens and turkeys fed inosine-supplemented
      diets. The first study consisted of 12 male chicks that were fed diets
      supplemented with 0.6 mol inosine or hypoxanthine per kilogram diet from 3- to 6
      week-old. Study 2 consisted of 12 turkey poults (toms) fed inosine-supplemented
      diets (0.7 mol/kg) from 6- to 8-week-old. Plasma allantoin and oxypurines
      concentrations were measured weekly using high performance liquid chromatography.
      Plasma uric acid (PUA) in chickens fed inosine-supplemented diets increased from
      0.31 to 1.34 mM (P<0.05) at the end of week 2. In turkeys, those fed control diet
      had 0.17 mM PUA concentration compared to 0.3 mM in those fed the inosine diet at
      week 2 (P<0.05). Allantoin concentration increased in chickens from week 1 to 2
      while a decrease was observed in turkeys (P<0.005) for both treatments. These
      data show that allantoin is present in turkey and chicken plasma. The presence of
      allantoin in avian plasma is consistent with uric acid acting as an antioxidant
      in these species.

PMID- 12798941
TI  - Identification of a new member of the GLWamide peptide family: physiological
      activity and cellular localization in cnidarian polyps.
AB  - KPNAYKGKLPIGLWamide, a novel member of the GLWamide peptide family, was isolated
      from Hydra magnipapillata. The purification was monitored with a bioassay:
      contraction of the retractor muscle of a sea anemone, Anthopleura fuscoviridis.
      The new peptide, termed Hym-370, is longer than the other GLWamides previously
      isolated from H. magnipapillata and another sea anemone, A. elegantissima. The
      amino acid sequence of Hym-370 is six residues longer at its N-terminal than a
      putative sequence previously deduced from the cDNA encoding the precursor
      protein. The new longer isoform, like the shorter GLWamides, evoked concentration
      dependent muscle contractions in both H. magnipapillata and A. fuscoviridis. In
      contrast, Hym-248, one of the shorter GLWamide peptides, specifically induced
      contraction of the endodermal muscles in H. magnipapillata. This is the first
      case in which a member of the hydra GLWamide family (Hym-GLWamides) has exhibited
      an activity not shared by the others. Polyclonal antibodies were raised to the
      common C-terminal tripeptide GLWamide and were used in immunohistochemistry to
      localize the GLWamides in the tissue of two species of hydra, H. magnipapillata
      and H. oligactis, and one species of sea anemone, A. fuscoviridis. In each case,
      nerve cells were specifically labeled. These results suggest that the GLWamides
      are ubiquitous among cnidarians and are involved in regulating the excitability
      of specific muscles.

PMID- 12798943
TI  - Characterization of digestive gland esterase-lipase activity of juvenile redclaw
      crayfish Cherax quadricarinatus.
AB  - Investigation of esterase-lipase activity in the digestive gland of redclaw
      crayfish Cherax quadricarinatus showed that the optimum enzyme activity occurred
      between 35 and 40 degrees C, with 100 mM NaCl at pH 8.5. Heavy metals completely
      inhibited and calcium ions partially inhibited enzyme activity. The enzyme
      activity diminished as the length of the fatty acid chain of substrates
      increased. Molecular masses for four isozymes were 43, 46, 63 and 118 kDa,
      respectively, as determined by PAGE.

PMID- 12798944
TI  - Characterization of serum immunoglobulin M of the Antarctic teleost Trematomus
      bernacchii.
AB  - Trematomus bernacchii immunoglobulin M concentration was determined in the serum
      by ELISA; the mean concentration value was 2.7 mg/ml corresponding to 9.6% of the
      total serum proteins. Purified IgM was analyzed by SDS-polyacrylamide gel
      electrophoresis, isoelectrofocusing and 2D electrophoresis. The relative
      molecular mass of the polymeric form was 830 kDa; that of separated H and L
      chains was, respectively, 78 and 25 kDa. The isoelectric points of the entire
      molecule ranged from 4.4 to 6.5, that of isolated H chains was between 4.0 and
      6.0. Separated H chains were shown to reaggregate in tetrameric form. The
      cleavage site of trypsin was at the end of the CH1 domain, as confirmed by the N
      terminal amino acid sequence of one of the resultant peptides. Immunoblotting was
      used to detect carbohydrates in the H and L chains labeled with digoxigenin.
      Glycosyl residues were detected only in the H chain. The carbohydrate content was
      evaluated to be 12.8% of the entire chain. Purified Igs were hydrolyzed by N
      glycosidase F at different conditions and at least four different hydrolytic
      sites were revealed by limited deglycosylation. T. bernacchii IgM was also
      compared to those of five other polar fish species.

PMID- 12798945
TI  - Partial purification and characterization of trimethylamine-N-oxide demethylase
      from lizardfish kidney.
AB  - Trimethylamine-N-oxide demethylase (TMAOase) from lizardfish (Saurida
      micropectoralis) was partially purified by acidification and diethylaminoethyl
      (DEAE)-cellulose chromatography. The enzyme was purified 82-fold with a yield of
      65.4%. The optimum pH and temperature were 7.0 and 50 degrees C, respectively.
      TMAOase was stable to heat treatment up to 50 degrees C and the activation energy
      was calculated to be 30.5 kJ mol(-1) K(-1). Combined cofactors (FeCl(2),
      ascorbate and cysteine) were required for full activation. FeCl(2) exhibited a
      higher stimulating effect on TMAOase activity than FeCl(3). At concentration less
      than 2 mM, ascorbate was more stimulatory to the activity than cysteine. The
      activity was tolerant of NaCl concentration up to 0.5 M. The enzyme had a K(m)
      for TMAO of 16.2 mM and V(max) of 0.35 micromol min(-1) and was able to convert
      TMAO to dimethylamine (DMA) and formaldehyde. The molecular mass of enzyme was
      estimated to be 128 kDa based on activity staining.

PMID- 12798946
TI  - Effects of dietary protein on the activity and mRNA level of trypsin in the
      midgut gland of the white shrimp Penaeus vannamei.
AB  - Protein food modulates the activity of proteases of the midgut gland of Penaeus
      vannamei. Shrimp fed with food containing 15, 30 and 50% protein exhibited
      differences in trypsin and chymotrypsin activity and trypsin mRNA levels. Shrimp
      fed with 30% protein showed higher trypsin and chymotrypsin activities than those
      fed 15 or 50% protein. An additional paralogue trypsin was observed with
      electrophoretic analysis in shrimp fed 30% protein. Shrimp fed 30% protein showed
      the highest trypsin to mRNA concentration, suggesting that trypsin genes
      expression is regulated transcriptionally.

PMID- 12798947
TI  - Distinct sucrose isomerases catalyze trehalulose synthesis in whiteflies, Bemisia
      argentifolii, and Erwinia rhapontici.
AB  - Isomaltulose [alpha-D-glucopyranosyl-(1,6)-D-fructofuranose] and trehalulose
      [alpha-D-glucopyranosyl-(1,1)-D-fructofuranose] are commercially valuable sucrose
      substitutes that are produced in several microorganisms by the palI gene product,
      a sucrose isomerase. Trehalulose also occurs in the silverleaf whitefly, Bemisia
      argentifoli, as the major carbohydrate in the insect's honeydew. To determine if
      the enzyme that synthesizes trehalulose in whiteflies was similar to the well
      characterized sucrose isomerase from microbial sources, the properties of the
      enzymes from whiteflies and the bacterium, Erwinia rhapontici, were compared.
      Partial purification of both enzymes showed that the enzyme from whiteflies was a
      116 kD membrane-associated polypeptide, in contrast to the enzyme from E.
      rhapontici, which was soluble and 66 kD. The enzyme from E. rhapontici converted
      sucrose to isomaltulose and trehalulose in a 5:1 ratio, whereas the enzyme from
      whiteflies produced only trehalulose. Unlike the E. rhapontici enzyme, the
      whitefly enzyme did not convert isomaltulose to trehalulose, but both enzymes
      catalyzed the transfer of fructose to trehalulose using sucrose as the glucosyl
      donor. The results indicate that trehalulose synthase from whiteflies is
      structurally and functionally distinct from the sucrose isomerases described in
      bacteria. The whitefly enzyme is the first reported case of an enzyme that
      converts sucrose to exclusively trehalulose.

PMID- 12798948
TI  - Molecular cloning and expression of pyruvate kinase from globefish (Fugu
      rubripes) skeletal muscle.
AB  - A cDNA clone encoding pyruvate kinase (PK) was isolated from a skeletal muscle
      cDNA library of globefish (Fugu rubripes), which is a kind of lower vertebrate.
      The full-length cDNA of globefish skeletal muscle pyruvate kinase (FM-PK) is
      approximately 2 kb and encodes a protein comprising 530 amino acids. The FM-PK
      gene is spanning approximately 4.8 kb and consists of 11 exons. FM-PK mRNA was
      detected in muscle and heart using Northern blots. The recombinant FM-PK (rFM-PK)
      was expressed in a baculovirus-insect cell system and purified using ion-exchange
      chromatography. The purified rFM-PK was shown to exist a 230 kDa homotetramer
      composed of 57 kDa subunits. Gel filtration showed 230000 as the tetramer of the
      subunit. The apparent K(m) (or S(0.5)) and the Hill coefficient for
      phosphoenolpyruvate (PEP) and ADP are 0.14 mM, 1.3 and 0.30 mM 0.98 at pH 7.4,
      respectively, when the enzyme is saturated with the second substrate. The rFM-PK
      is strongly activated by fructose-1,6-bisphosphate, the apparent K(m) for PEP
      changes to 0.059 mM and the Hill coefficient to 1.1. ATP, which is the product of
      the enzyme reaction, inhibits activity. This is the first report to show the full
      length cDNA and amino acid sequence of PK for a species of fish.

PMID- 12798949
TI  - Differential modulation of apoptosis-associated proteins by ethanol in rat
      cerebral cortex and cerebellum.
AB  - Chronic ethanol treatment caused a differential modulation of apoptosis
      associated proteins, cytochrome c release, concomitant with procaspase-9 and
      procaspase-3 activation leading to oligonucleosomal DNA fragmentation in rat
      cerebral cortex and cerebellum. Caspase-3 proform (32 kDa) showed decreased
      immunoreactivity in cortex and cerebellum, while the cleaved active fragment (17
      kDa) increased significantly in cerebellum after ethanol treatment. Further,
      chronic ethanol treatment increased caspase-3 activity in cortex and to a higher
      extent in cerebellum, which was further confirmed by blocking experiments with
      caspase-3 specific inhibitor, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO). We
      tested whether activated caspase-3 cleaves downstream substrates such as poly
      (ADP-ribose) polymerase-1 and protein kinase C-delta (PKC-delta). Western blots
      showed poly (ADP-ribose) polymerase-1 cleavage to its signature fragment of 85
      kDa and decreased levels of PKC-delta in cerebral cortex and cerebellum after
      ethanol treatment, suggestive of caspase-3 activation. Elevated caspase-3
      activity in cerebellum than cortex correlating with cytochrome c, caspase-9,
      active caspase-3 (p17), poly (ADP-ribose) polymerase-1 and PKC-delta data,
      suggests a mechanism by which ethanol might be exerting pro-apoptotic events in
      brain and how selective brain regions such as cerebellum are vulnerable to
      ethanol neurotoxicity in terms of cell death.

PMID- 12798950
TI  - Immature human osteoblastic MG63 cells predominantly express a subtype 1-like
      CGRP receptor that inactivates extracellular signal response kinase by a cAMP
      dependent mechanism.
AB  - Although accumulated data suggest that calcitonin gene-related peptide (CGRP)
      produces anabolic effects in skeletal tissue by directly acting on osteogenic
      cells, neither the distribution of CGRP receptor subtypes nor the associated
      cellular signaling pathways are well understood. In this study, we have
      pharmacologically and biochemically characterized CGRP-binding sites in immature
      human osteoblastic MG63 cells. In a [125I]CGRP whole-cell-binding assay,
      nonlinear regression curve-fitting analysis demonstrated a single binding site
      (K(D)=405+/-29 pM; 13,100+/-223 sites per cell). Immunocytochemical and Western
      blot analyses demonstrated that 48-, 52-, and 120-kDa forms of the calcitonin
      receptor-like receptor (CRLR) and a 15-kDa form of the receptor-activity
      modifying protein-1 (RAMP-1) was expressed on the plasma membrane. CGRP strongly
      stimulated cellular cAMP production and this effect was antagonized not only by
      an antagonist of the subtype-1 CGRP (CGRP(1)) receptor, CGRP-(8-37), but by an
      agonist of the putative subtype-2 CGRP (CGRP(2)) receptor, [Cys(Acm)(2,7)]-CGRP,
      that also itself acted as a weak agonist. In contrast to published data, CGRP
      dose- and time-dependently dephosphorylated and inactivated extracellular signal
      response kinase (ERK). This action was blocked by CGRP-(8-37), by an inhibitor of
      cAMP-dependent protein kinase (H-89), or by an inhibitor of protein phosphatases
      (vanadate). Prolonged CGRP treatments significantly suppressed DNA synthesis at
      27 h, but up-regulated type I collagen. Both these actions were blocked by CGRP
      (8-37) and mimicked by a specific inhibitor of ERK (PD98059). In summary, our
      data suggest that the CGRP receptors in MG63 cells meet many, but not all, of the
      classical criteria used to define CGRP(1) receptors. These receptors that
      functioned in a pharmacologically distinct manner could inhibit cell
      proliferation, and were substantially more sensitive to a CGRP(2) receptor
      agonist than are typical CGRP(1) receptors. These receptor proteins were not
      exactly matched with the known components of a CGRP(1) receptor that have been
      reported. Therefore, it is possible that the CGRP receptors expressed in immature
      osteoblastic human MG63 cells represent a variation of the known CGRP(1)
      receptor.

PMID- 12798951
TI  - Activation of spinal histamine H3 receptors inhibits mechanical nociception.
AB  - Previous studies have suggested a possible pain-modulatory role for histamine
      H(3) receptors, but the localization of these receptors and nature of this
      modulation is not clear. In order to explore the role of spinal histamine H(3)
      receptors in the inhibition of nociception, the effects of systemically
      (subcutaneous, s.c.) and intrathecally (i.t.) administered histamine H(3)
      receptor agonists were studied in rats and mice. Immepip (5 mg/kg, s.c.) produced
      robust antinociception in rats on a mechanical (tail pinch) test but did not
      alter nociceptive responses on a thermal (tail flick) test. In contrast, this
      treatment in mice (immepip, 5 and 30 mg/kg, s.c.) did not change either
      mechanically or thermally evoked nociceptive responses. When administered
      directly into the spinal subarachnoid space, immepip (15-50 microg, i.t.) and R
      alpha-methylhistamine (50 microg, i.t.) had no effect in rats on the tail flick
      and hot plate tests, but produced a dose- and time-dependent inhibition (90-100%)
      of nociceptive responses on the tail pinch test. This attenuation was blocked by
      administration of thioperamide (10 mg/kg, s.c.), a histamine H(3) receptor
      antagonist. Intrathecally administered thioperamide also reversed antinociceptive
      responses induced by systemically administered immepip, which demonstrates a
      spinal site of action for the histamine H(3) receptor agonist. In addition,
      intrathecally administered immepip (25 microg) produced maximal antinociception
      on the tail pinch test in wild type, but not in histamine H(3) receptor knockout
      (H(3)KO) mice. These findings demonstrate an antinociceptive role for spinal
      histamine H(3) receptors. Further studies are needed to confirm the existence of
      modality-specific (i.e. mechanical vs. thermal) inhibition of nociception by
      these receptors, and to assess the efficacy of spinally delivered histamine H(3)
      receptor agonists for the treatment for pain.

PMID- 12798952
TI  - Modification of morphine analgesia and tolerance by flumazenil in male and female
      rats.
AB  - This study assessed the effect of the central benzodiazepine receptor antagonist,
      8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3
      carboxylic acid ethyl ester (flumazenil), on morphine-induced analgesia,
      locomotor effects, and development of tolerance in rats. The thermally evoked
      pain (tail flick) response was determined after acute and chronic intraperitoneal
      (i.p.) administration of morphine and flumazenil, alone and in combination. In
      acute studies, flumazenil induced weak analgesia unrelated to dose and sex,
      whereas morphine-induced analgesia was dependent on both dose and sex
      (male>female). Flumazenil dose-dependently enhanced the analgesic effect of
      morphine in female but not in male rats. Isobolographic analysis suggested
      synergism between flumazenil and morphine in female rats, but antagonism in male
      rats. Flumazenil-induced locomotor changes (alone and with morphine) were related
      to sex but not dose. Chronic coadministration of flumazenil with morphine
      enhanced analgesia and attenuated tolerance development in female rats. The
      findings suggest a possible role for flumazenil as an adjunct with opioids in
      acute and chronic pain therapy.

PMID- 12798953
TI  - Interactions of gamma-hydroxy butyrate with ethanol and NCS 382.
AB  - We examined the effects of gamma-hydroxy butyrate (GHB) alone and in combination
      with either ethanol or NCS 382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H
      benzo[a][7]annulen-6-ylidene], a purported antagonist at the GHB receptor. These
      effects were examined on the responding of rats under a fixed-ratio (FR) 10
      schedule of sugar solution (14%, w/v; 0.1 ml) presentation. GHB dose-relatedly
      decreased responding. When GHB was combined with ethanol, the effects of the two
      drugs were less than additive. NCS 382 did not antagonize the rate-decreasing
      effects of GHB. These observations are consistent with the notion that many of
      the behavioral actions of exogenously administered GHB result from GHB's actions
      at sites other than the GHB receptor, and are inconsistent with the popular
      notion that the effects of GHB and ethanol are synergistic.

PMID- 12798954
TI  - Multiple cellular electrophysiological effects of azimilide in canine cardiac
      preparations.
AB  - The cellular electrophysiological effect of azimilide (0.1-30 microM) was
      analyzed in canine ventricular preparations by applying the standard
      microelectrode and patch-clamp techniques at 37 degrees C. In papillary muscle,
      the drug prolonged the action potential duration (APD) in a concentration
      dependent manner at a cycle length (CL) of 1000 ms. In Purkinje fibers, at the
      same CL, the concentration-dependent lengthening of the APD was observed in the
      presence of up to 3 microM azimilide (at 3.0 microM: 24.1+/-4.2%, n=9); at higher
      drug concentration, no further APD prolongation was observed. Azimilide
      lengthened APD in a reverse frequency-dependent manner in papillary muscle and
      Purkinje fibers alike. Azimilide (10 microM) caused a rate-dependent depression
      in the maximal upstroke velocity of the action potential (V(max)) in papillary
      muscle. The time and rate constants of the offset and onset kinetics of this
      V(max) block were 1754+/-267 ms (n=6) and 5.1+/-0.4 beats (n=6), respectively.
      Azimilide did not prevent the APD shortening effect of 10 microM pinacidil in
      papillary muscle, suggesting that the drug does not influence the ATP-sensitive
      K(+) current. Azimilide inhibited the rapid (I(Kr)) and slow component (I(Ks)) of
      the delayed rectifier K(+) current and the L-type Ca(2+) current (I(Ca)). The
      estimated EC(50) value of the drug was 0.59 microM for I(Ks), 0.39 microM for
      I(Kr) and 7.5 microM for I(Ca). The transient outward (I(to)) and the inward
      rectifier (I(k1)) K(+) currents were not influenced by the drug. It is concluded
      that the site of action of azimilide is multiple, it inhibits not only K(+)
      (I(Kr), I(Ks)) currents but, in higher concentrations, it also exerts calcium-
      and use-dependent sodium channel block.

PMID- 12798955
TI  - Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ
      receptor, in conscious rats.
AB  - Apelin is an endogenous depressor peptide for the G protein-coupled APJ receptor.
      Our hypothesis is that apelin is a venodilator, and it reduces mean circulatory
      filling pressure (MCFP; index of venous tone). Dose-response curves of apelin
      (10, 20 and 40 nmol/kg) or vehicle (0.9% NaCl) were constructed in two groups
      each of conscious, unrestrained rats: unblocked rats and rats pretreated with
      mecamylamine (Mec; ganglionic blocker) and noradrenaline (NA; to restore vascular
      tone). The vehicle had no effects in the unblocked or ganglionic-blocked rats.
      Apelin decreased mean arterial pressure (MAP) and increased heart rate (HR), but
      it did not alter mean circulatory filling pressure in the unblocked rats. In the
      ganglionic-blocked rats, apelin did not alter heart rate but decreased mean
      arterial pressure and mean circulatory filling pressure. These results show that
      apelin is an arterial and venous dilator in vivo. The depressor effect of apelin
      is accompanied by tachycardia which is abolished by ganglion blockade.

PMID- 12798957
TI  - Relaxant and Ca2+ channel blocking properties of norbormide on rat non-vascular
      smooth muscles.
AB  - We have investigated the effects of the rat-specific vasoconstrictor agent
      norbormide on the mechanical and electrophysiological properties of rat non
      vascular smooth muscles. Norbormide (50 microM) did not affect the resting tone
      of urinary bladder, tracheal, and duodenal rings. In all tissues, KCl-induced
      concentration-response curves were shifted downward by norbormide (5 and 50
      microM). In urinary bladder and tracheal rings, norbormide inhibited contractile
      responses to carbachol only at the higher concentration (50 microM). In single
      gastric fundus myocytes, 50 microM norbormide inhibited L-type Ca(2+) current
      (I(Ca(L))) by about 60%, neither affecting both activation and inactivation rates
      of the current nor the current-voltage curve along the voltage axis. Our results
      indicate that rat non-vascular smooth muscles are relaxed by norbormide with a
      mechanism likely involving a reduction of Ca(2+) entry through L-type Ca(2+)
      channels.

PMID- 12798956
TI  - The administration of alpha-melanocyte-stimulating hormone protects the
      ischemic/reperfused myocardium.
AB  - The contribution of alpha-melanocyte-stimulating hormone (alpha-MSH) treatment,
      an active fragment of adrenocorticotropic hormone (ACTH), to the recovery of
      postischemic cardiac function, infarct size, the incidence of reperfusion-induced
      ventricular fibrillation and apoptotic cell death was studied in
      ischemic/reperfused isolated rat hearts. Rats were subcutaneously injected with
      40, 200 and 400 microg/kg of alpha-MSH, and 12 h later, hearts were isolated,
      perfused and subjected to 30 min of ischemia followed by 120 min of reperfusion.
      Thus, after 120 min of reperfusion, with the concentration of 200 microg/kg alpha
      MSH, coronary flow, aortic flow and left ventricular developed pressure were
      significantly improved from their control values of 14.6+/-0.6 ml/min, 7.5+/-0.5
      ml/min and 9.1+/-0.4 kPa to 20.2+/-0.4 ml/min (p<0.05), 31.5+/-0.9 ml/min
      (p<0.05) and 15.9+/-0.6 (p<0.05) kPa, respectively. With the doses of 40, 200 and
      400 microg/kg of alpha-MSH, infarct size was reduced from its control value of
      38+/-5% to 33+/-6% (NS), 17+/-3% (p<0.05) and 19+/-4% (p<0.05), respectively. The
      reduction in the incidence of reperfusion-induced ventricular fibrillation
      followed the same pattern. It is reasonable to assume that a reduction in infarct
      size, in the alpha-MSH-treated myocardium, resulted in a reduction as well in
      apoptotic cell death. Although we did not specifically study the exact
      mechanism(s) of alpha-MSH-afforded postischemic protection, we assume that this
      protection may be related to alpha-MSH-induced corticosterone release and
      corticosterone-induced de novo protein synthesis, which reflected in the recovery
      of postischemic cardiac function in isolated hearts. Thus, interventions that are
      able to increase plasma corticosterone or glucocorticoid release may prevent the
      development of ischemia/reperfusion-induced damage.

PMID- 12798958
TI  - Therapeutic treatment with heat-killed Mycobacterium vaccae (SRL172) in a mild
      and severe mouse model for allergic asthma.
AB  - The hypothesis that a lack of early childhood bacterial infections would favor
      the development of allergic disease suggests that bacteria can be used as a
      potential treatment for allergic asthma. Therefore, in this study, we
      investigated the therapeutic potential of heat-killed Mycobacterium vaccae in two
      mouse models of allergic asthma. For this purpose, mice were sensitized i.p. with
      ovalbumin/alum (severe model) or ovalbumin alone (mild model) and challenged on
      days 77, 80 and 83 by inhalation of either ovalbumin or saline aerosols.
      Treatment of mice with M. vaccae (s.c. 10(7) or 10(8) colony-forming units) on
      days 56 and 63, however, did not reduce airway hyperresponsiveness and
      eosinophilia, IgE and interleukin-5 production 24 h after ovalbumin challenge in
      either mouse model. We therefore conclude that treatment of sensitized mice with
      M. vaccae before allergen exposure is not able to reduce the allergic and asthma
      like response in a mild and a severe model of allergic asthma.

PMID- 12798960
TI  - Differential effects on cognitive functioning in 13- to 16-year-olds prenatally
      exposed to cigarettes and marihuana.
AB  - Cognitive performance was examined in 145 thirteen- to sixteen-year-old
      adolescents for whom prenatal exposure to marihuana and cigarettes had been
      ascertained. The subjects were from a low-risk, predominantly middle-class sample
      participating in an ongoing, longitudinal study. The assessment battery included
      tests of general intelligence, achievement, memory, and aspects of executive
      functioning (EF). Consistent with results obtained at earlier ages, the strongest
      relationship between prenatal maternal cigarette smoking and cognitive variables
      was seen with overall intelligence and aspects of auditory functioning whereas
      prenatal exposure to marihuana was negatively associated with tasks that required
      visual memory, analysis, and integration. The interpretation of the results is
      discussed in terms of the differential observations related to in utero exposure
      to cigarettes and marihuana and the nature of the cognitive variables associated
      with the two drugs.

PMID- 12798959
TI  - Learning impairment caused by a toxin produced by Pfiesteria piscicida infused
      into the hippocampus of rats.
AB  - Pfiesteria piscicida, an estuarine dinoflagellate, which has been shown to kill
      fish, has also been associated with neurocognitive deficits in humans. With a rat
      model, we have demonstrated the cause-and-effect relationship between Pfiesteria
      exposure and learning impairment. In several studies, we have replicated the
      finding in Sprague-Dawley rats that exposure to fixed acute doses of Pfiesteria
      cells or filtrates caused radial-arm maze learning impairment. Recently, this
      finding of Pfiesteria-induced learning impairment in rats has been independently
      replicated in another laboratory as well. We have demonstrated significant
      Pfiesteria-induced learning impairment in both the win-shift and repeated
      acquisition tasks in the radial-arm maze and in reversal learning in a visual
      operant signal detection task. These learning impairments have been seen as long
      as 10 weeks after a single acute exposure to Pfiesteria. In the current study, we
      used a hydrophilic toxin isolated from clonal P. piscicida cultures (PfTx) and
      tested its effect when applied locally to the ventral hippocampus on repeated
      acquisition of rats in the radial-arm maze. Toxin exposure impaired choice
      accuracy in the radial-arm maze repeated acquisition procedure. The PfTx-induced
      impairment was seen at the beginning of the session and the early learning
      deficit was persistent across 6 weeks of testing after a single administration of
      the toxin. Eventually, with enough practice, in each session, the PfTx-exposed
      rats did learn that session's problem as did control rats. This model has
      demonstrated the cause-and-effect relationship between exposure to a hydrophilic
      toxin produced by P. piscicida and learning impairment, and specifically that the
      ventral hippocampus was critically involved.

PMID- 12798961
TI  - The effects of prenatal cocaine exposure on reversal learning using a simple
      visual discrimination task in rhesus monkeys.
AB  - The purpose of this research was to determine if adult animals that were exposed
      to cocaine prenatally would be able to adapt to changes in the rules of
      reinforcement for a simple discrimination task. Treatment groups included 0.0,
      1.0, and 3.0 mg cocaine/kg/day and an escalating-dose group that began treatment
      at 3.0 mg cocaine/kg/day, after which the dose was increased by 0.5 mg
      cocaine/kg/day every 2 weeks throughout the pregnancy. All animals performed a
      color and position discrimination task for food reinforcers for approximately 6
      years before the present study. For this task, subjects were presented with
      colored stimuli that determined the correctness of subsequent position choices:
      left for red or yellow and right for blue or green. At 7 years of age, the rules
      for obtaining reinforcement were reversed. Animals exposed to all doses of
      cocaine showed impaired reversal performance. Further, animals exposed to the
      escalating doses of cocaine continued to show this impairment for over 285
      sessions (about 21/2 years). The number of sessions required by subjects to
      master these contingency changes indicated that, using a task with which they
      have an extensive history, cocaine-exposed animals have greater difficulty in
      adapting to important changes in their environment.

PMID- 12798962
TI  - Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol
      exposure on the developing rat hippocampus.
AB  - Children with fetal alcohol syndrome (FAS) display altered performance in tasks
      of learning and memory, behaviours thought to be associated with the hippocampus.
      Altered hippocampal structure has been reported in some FAS children; therefore,
      a rat model system was used to determine whether the size and numbers of
      pyramidal cells in regions CA1 and CA3 of the hippocampal formation and granule
      cells in the dentate gyrus were altered by alcohol exposure during different
      periods of development. Rat pups were exposed to alcohol in utero during the
      second trimester-equivalent (E10-20), the first two trimesters-equivalent (E1
      20), during the time of hippocampal pyramidal cell neurogenesis (E16-20), part of
      the third trimester-equivalent (P4-9), and all three trimesters-equivalent (E1
      20+P4-9). Control animals (nutritional and untreated) were reared for all
      treatment conditions. All pups were perfused on P10. CA1 volume, pyramidal cell
      density, and number were reduced in pups treated with alcohol during the third
      trimester-equivalent, whether unique or as exposure during all three trimesters
      equivalent. CA3 volume was reduced in alcohol-treated animals across all
      gestational ages; however, pyramidal cell density and number in this region were
      only reduced in animals treated with alcohol during the third trimester
      equivalent. Volume of the dentate gyrus did not appear to be affected by alcohol
      treatment. Granule cell density and number in this region were reduced in animals
      treated with alcohol during the third trimester-equivalent. The third trimester
      equivalent in the rat appears to be a developmental period during which the
      hippocampus is particularly susceptible to the effects of alcohol consumption.
      The resulting damage to the hippocampus may contribute to the behavioural
      deficits related to learning and memory noted in children with FAS.

PMID- 12798963
TI  - Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial
      and visual reversal learning in rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental
      contaminant that has been shown to alter spatial and visual learning following
      developmental exposure. The current study examined the effects of gestational and
      lactational exposure to TCDD on spatial and visual discrimination/reversal
      learning (spatial and visual RL) in rats using two-lever operant testing
      chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1
      microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One
      male and one female from each litter were tested beginning at 100 days of age.
      For spatial RL, animals were reinforced for pressing the lever associated with
      the correct spatial location (either left or right). For visual RL, the animals
      were reinforced for pressing the lever associated with the correct visual
      stimulus (either the illuminated or nonilluminated cuelight). After reaching 85%
      correct for two consecutive days, the opposite spatial location or visual cue was
      reinforced. Five reversals were conducted for spatial RL, and two reversals for
      visual RL. For spatial RL, there were no differences between the TCDD-exposed and
      control rats in total number of errors committed. However, an in-depth analysis
      of errors in four different phases of the learning process revealed that TCDD
      exposed rats made more errors early in learning when they were just beginning to
      learn the new reinforcement contingencies. The importance of this increase in
      errors during the initial stage of learning is unclear, given that there was no
      increase in overall errors to criterion. For visual RL, there was a reduction in
      errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed
      females exhibited a reduction in errors on the second reversal. Subsequent
      response pattern analyses revealed that the facilitation in performance was due
      to a more rapid transition through the early phase of learning. Why males were
      improved on OL and females were not until the second reversal is unknown, but the
      different patterns could reflect differences in learning style in male and female
      rats. In keeping with previous research, the results of the current study
      underscore the fact that (1) alterations in cognitive function observed following
      early TCDD exposure are very subtle and (2) under some conditions, learning is
      actually facilitated, rather than impaired, in TCDD-exposed animals.

PMID- 12798964
TI  - Low doses of non-NMDA glutamate receptor agonists alter neurobehavioural
      development in the rat.
AB  - While it is known that glutamate is critical to CNS development and function,
      less is known about the role of kainate receptors, a subclass of ionotropic
      glutamate receptors, during ontogeny. This is especially true with respect to the
      emergence and expression of behaviour. It is also known that the neonatal CNS
      differs from that of adults with respect to excitatory amino acid (EAA) toxicity.
      Our aim was to determine the effects of early low-dose stimulation of kainate
      receptors on physical and behavioural development in the rat. Saline, one of two
      subtoxic doses of domoic acid (DOM) (5 and 20 microg/kg), or in a parallel study,
      saline, or one of two pharmacologically equivalent doses of kainic acid (KA) (25
      and 100 microg/kg), were systemically administered once daily from postnatal days
      (PNDs) 8-14. While DOM or KA had no effect on typical measures of toxicity such
      as weight gain, acoustic startle, ultrasonic vocalizations (UVs), or maternal
      retrieval, these doses were shown to be physiologically relevant, producing
      particular group differences in eye opening, conditioned place preference, and
      activity levels. We conclude that administration of very low doses of selective
      kainate receptor agonists during the second postnatal week produces changes in
      neurobehavioural development in the rat.

PMID- 12798965
TI  - Acquisition, steady-state performance, and the effects of trimethyltin on the
      operant behavior and hippocampal GFAP of Long-Evans and Fischer 344 rats.
AB  - Strain differences represent an overlooked variable that may play an important
      role in neurotoxic outcomes that can impact regulatory decision making. Here, we
      examined the strain-dependent effects of trimethyltin (TMT), a compound used as a
      positive control for behavioral and neurochemical assessments of neurotoxicity.
      Adult male Long-Evans (LE) and Fischer 344 (F344) rats (n=12 each) were trained
      to respond under a multiple, fixed-interval 3-min fixed-ratio 10-response (multi
      FI 3-min FR10) schedule of milk reinforcement. Acquisition was characterized by
      time-dependent changes in several behavioral endpoints in both strains, although
      rate of acquisition of the fixed-interval pattern of responding was slower in
      F344 rats. Steady-state (baseline) performance was characterized by slower
      overall rates of responding in F344 rats. There was little evidence of strain
      differences in many of the other baseline performance measures. Rats of each
      strain were then divided into two equal groups that received either 1 ml/kg
      saline or 8.0 mg/kg iv TMT approximately 18 h before the next test session. TMT
      produced transient changes in the performance of LE and F344 rats that lasted for
      several sessions. For many behavioral measures, F344 rats were more affected by
      TMT than were LE rats. TMT-induced reactive gliosis, as assessed by assaying
      glial fibrillary acidic protein (GFAP), was also greater in F344 rats than in LE
      rats. These results suggest F344 rats may be more susceptible to TMT-induced
      neurotoxicity than are LE rats.

PMID- 12798966
TI  - Dietary ethinyl estradiol exposure during development causes increased voluntary
      sodium intake and mild maternal and offspring toxicity in rats.
AB  - Exogenous estrogen exposure during development often results in behavioral
      masculinization and/or defeminization of genetic females. Genetic males may be
      defeminized, hypermasculinized or even demasculinized after similar treatment.
      Here, pregnant Sprague-Dawley rats consumed phytoestrogen-free diets containing
      0, 1, 5 or 200 ppb EE(2) beginning on gestational day (GD) 7. Offspring were
      weaned to the same maternal diet and maintained gonadally intact. There were mild
      effects on body weight and food consumption in dams of the 200 ppb group and
      their offspring weighed less at birth than those of the control group; however,
      gross assessments of nursing behavior were normal in all dietary groups.
      Postweaning, offspring of the 200 ppb group weighed less and consumed less food
      than controls. There were no EE(2)-related effects on open-field activity (tested
      at postnatal days (PND) 22-24, 43-45 and 64-66), play behavior (tested at PND
      35), running wheel activity (PND 63-77) or intake of a 0.3% saccharin-flavored
      solution (PND 69-71). Intake of a 3.0% sodium chloride-flavored solution on PND
      73-75 was increased in both male and female offspring of the 200 ppb group
      relative to same-sex controls, an effect that is reportedly estrogen mediated.
      Sodium chloride-flavored solution intake is a sexually dimorphic behavior for
      which female rats consume more than males. Here, while EE(2) exposure had few
      effects on the conventional tests of sexually dimorphic behaviors, exposure to
      200 ppb in the diet appeared to feminize genetic males and hyperfeminize genetic
      females with regard to sodium intake.

PMID- 12798968
TI  - Relation among alcohol dehydrogenase 2 polymorphism, alcohol consumption, and
      levels of gamma-glutamyltransferase.
AB  - In human beings, alcohol is metabolized primarily by alcohol dehydrogenase 2
      (ADH2) and acetaldehyde dehydrogenase 2 (ALDH2). Whereas polymorphisms of the
      ALDH2 are common in Asian persons, polymorphisms of the ADH2 seem to be more
      important in Caucasian individuals. The aim of this study was to assess the
      relation among ADH2 polymorphism, alcohol consumption, and levels of gamma
      glutamyltransferase (GGT). The question was examined among 1,663 subjects (736
      men and 927 women) participating in a national representative health and
      nutrition survey (VERA substudy of the German National Nutrition Survey). Alcohol
      consumption was assessed through responses to a semiquantitative food frequency
      questionnaire (FFQ), and the ADH2 restriction fragment length polymorphism (RFLP)
      Mae III and GGT levels were analyzed from frozen serum samples. The relations
      between the polymorphism and alcohol consumption and between alcohol consumption
      and GGT levels according to the polymorphism were assessed with the use of
      descriptive statistics and contingency table analysis. Of the subjects studied,
      2.8% were homozygous or heterozygous for the ADH2*2 allele, and high levels of
      alcohol consumption (>20 g/day) were less common among these subjects (8.5%) than
      among subjects with the ADH2*1 allele (19.9%). Median levels of GGT increased
      with increasing levels of alcohol consumption. This increase tended to be
      stronger among subjects with the ADH2*2 allele than among other subjects,
      although differences were not statistically significant (P value for
      interaction=.1) given the small number of subjects with the polymorphism. These
      results are consistent with the hypothesis that subjects with the ADH2*2 allele,
      on the one hand, might tend to drink less alcohol but, on the other hand, might
      be at increased risk of alcohol-related effects on the liver with consumption of
      larger amounts of alcohol. However, this hypothesis needs to be evaluated among
      larger population samples.

PMID- 12798967
TI  - Prognosis of adult men with heat exhaustion with regard to postural stability and
      neurobehavioral effects: a 6-month follow-up study.
AB  - The medical complications of heat disorders, including hematological,
      cardiovascular and renal damage, have been well documented. However, very little
      has been written on its neurological complications. In an earlier study, we
      reported that men with heat exhaustion, studied 2 weeks after the acute episode,
      had significantly more symptoms of neurasthenia, poorer performance in short-term
      memory and slower reaction time. The cases (as a group) had significantly poorer
      postural stability. The objective of this study was to assess the prognosis of
      men with heat exhaustion with regard to postural stability and neurobehavioral
      functions 12, 3 and 6 months after the acute episode. The study is prospective in
      design and spans a 2-year period. All soldiers who were diagnosed to have heat
      exhaustion (cases) from 1 March 1998 were included in the study. For each case, a
      healthy soldier (matched for age, ethnicity, years of education and military
      vocation) was recruited to serve as control. Each subject had a neurobehavioral
      assessment by using the Swedish Performance Evaluation System (SPES), a
      computerized test battery. The postural stability of the subjects was assessed
      using a computerized postural sway system. Each subject took the test 2 weeks
      after the acute episode and repeated the test 3 and 6 months later for duration
      of 2 years. We report here the findings of 21 heat exhaustion cases and 18
      controls, which completed all the three tests (i.e. done 2 weeks after the acute
      episode and 3 and 6 months later). Significant differences were only detected in
      some of the neurobehavioral and neurophysiological parameters between the cases
      and the control for first two tests but not the third test. The prognosis of
      adult with heat exhaustion is good. There were no significant differences in
      neurobehavioral tests and postural stability among the cases and controls 612
      months after the episode.

PMID- 12798969
TI  - Effects of concurrent access to a single concentration or multiple concentrations
      of ethanol on the intake of ethanol by male and female periadolescent alcohol
      preferring (P) rats.
AB  - The objectives of this study were to assess the effects of access to different
      concentrations of ethanol and sex of the animal on ethanol consumption during
      periadolescence [postnatal days (PNDs) 30-60] in alcohol-preferring (P) rats. On
      PND 28, female and male P pups were single housed in hanging stainless steel
      cages with ad libitum access to water and food. Beginning on PND 30, the rats
      were also given access to either a single concentration [15% volume/volume
      (vol./vol.)] or multiple concentrations [10%, 20%, and 30% (vol./vol.)] of
      ethanol. Differences between sex (male vs. female) and ethanol conditions (single
      concentration vs. multiple concentrations), for the average amount of ethanol
      consumed for each week (starting on PND 33) of access, were examined. Analyses of
      the data for ethanol drinking revealed significant (P<.025) main effects of week
      and ethanol condition, as well as a significant weekxethanol condition
      interaction. For the first week, both male and female P pups consumed more
      ethanol under the multiple-ethanol-concentration condition than under the single
      ethanol-concentration condition. However, across the second through fourth weeks,
      this pattern was seen only in female P pups. When preference for one
      concentration of ethanol over the other concentrations was assessed, it was found
      that male P pups tended to choose the 30% concentration over the 10% and 20%
      concentrations, whereas female P pups did not display a preference. The findings
      of this study corroborate previous work indicating that periadolescent P rats
      readily acquire high-ethanol-drinking behavior and that, similar to adult P rats,
      concurrent access to multiple concentrations of ethanol further enhances ethanol
      intake. These findings suggest to us that innate genetically influenced
      mechanisms promoting high ethanol intake are present at this stage of
      development.

PMID- 12798970
TI  - Minimal exposure to ethanol increases ethanol preference in Maudsley reactive
      male rats.
AB  - Male Maudsley reactive (MR/Har) rats often exhibit marked ethanol or alcohol
      preference (AP) after forced (one-bottle) exposure to 10% [volume/volume
      (vol./vol.)] ethanol, but exhibit variable AP without this exposure. In this
      study, we examined manipulations of one-bottle exposure to ethanol (10% ethanol
      as the sole source of fluid) in three experiments. In Experiment 1, we recorded
      voluntary consumption of 10% ethanol during 5 weeks of two-bottle choice in male
      and female MR/Har rats after 0, 1, 2, 3, or 4 days of one-bottle ethanol
      exposure. The results showed that, in male rats, one day of one-bottle exposure
      was as effective as multiple days in increasing AP relative to findings for
      ethanol-naive (control) rats. Female rats were not affected by one-bottle
      exposure. They drank equal amounts of ethanol across all groups and in greater
      amounts than observed for male rats (relative to body weight). The results of
      Experiment 2 supported the suggestion that 18 h of exposure to ethanol was
      similar to 24 h of exposure for increasing subsequent ethanol consumption, and
      that 12 h of exposure increased AP relative to findings for ethanol-naive rats,
      but on a delayed basis and at a lower level than that observed for 24 h of
      exposure. In Experiment 3, we tested whether these increases in ethanol
      consumption, observed in male MR/Har rats after one-bottle exposure to ethanol,
      might be related to habituating to an unpalatable substance. Thus, rats had one
      bottle tests with either a 10% ethanol solution (as in earlier studies) or a 0.01
      mmol quinine solution, after which groups of rats were tested for voluntary
      consumption (two-bottle test) of one of these solutions and water. Results showed
      that although rats in the quinine-exposed group drank more fluid than that
      consumed by rats in the ethanol-exposed group during the one-bottle period, rats
      preferred ethanol to water and avoided quinine relative to water during the 5
      weeks of two-bottle choice. The results seem to indicate that relatively small
      amounts of 10% ethanol can markedly increase subsequent AP in male MR/Har rats,
      and that this increase in AP does not seem to be attributable to a process of
      habituating to an unpalatable fluid.

PMID- 12798971
TI  - Effects of ethanol and ipsapirone on the development of midline raphe glial cells
      and astrocytes.
AB  - Previously, results of studies from our laboratory have shown that the offspring
      of ethanol-fed female rats have a significant decrease in serotonin (5-HT)
      neurons and glia that contain S100B, an essential trophic factor for the
      development of 5-HT neurons. The deficiency of S100B-immunopositive glia was
      detected during the vulnerable period in 5-HT neuron development and in brain
      areas proximal to these neurons. The reductions of both 5-HT neurons and S100B
      positive glia were prevented by maternal treatment with a 5-HT(1A) agonist (i.e.,
      ipsapirone or buspirone). In the current study, we investigated whether the
      offspring of ethanol-fed rats had a general decrease in the density of glial
      cells in the brain areas that contain 5-HT neurons, and we determined whether
      these changes were prevented by maternal treatment with ipsapirone between
      gestational days (GDs) 13 and 20. We estimated the density of vimentin-positive
      glia of the midline raphe glial structure (MRGS) at GD 20 and postnatal day (PND)
      5 and of glial fibrillary acidic protein (GFAP)-positive astrocytes proximal to
      the dorsal and median raphe at PNDs 5 and 19. The results of this study provide
      evidence that in utero ethanol exposure is associated with a reduced density of
      GFAP-immunopositive astrocytes proximal to the dorsal and median raphe. Maternal
      ipsapirone treatment significantly increased astroglial density in the dorsal
      raphe at PNDs 5 and 19 and in the median raphe at PND 5, such that it either
      prevented (dorsal raphe, PNDs 5 and 19) or blunted (median raphe, PND 5) the
      effects of ethanol.

PMID- 12798972
TI  - Blood ethanol concentration profiles: a comparison between rats and mice.
AB  - It is important to select an appropriate model system for studies examining the
      mechanisms of ethanol-induced injury. The most common model systems use either
      mice or rats with ethanol administered by means of intragastric gavage or
      intraperitoneal injection, yet few studies have compared directly the blood
      ethanol concentration (BEC) profiles that result from each of these model
      systems. In the current study, Sprague-Dawley rats and C57BL/6J mice were given
      ethanol by means of intragastric gavage or intraperitoneal injection at 40 days
      of age. Blood samples were collected at consistent time intervals to determine
      BECs. Blood ethanol concentrations in mice were sharper, with a more rapid rise
      to a sharp peak BEC, followed by a relatively rapid decline. In contrast, rat BEC
      profiles showed an initial rapid rise, followed by a more gradual rise to peak
      concentrations, and, then, a relatively gradual decline. This difference was
      particularly evident in rats receiving ethanol intragastrically. The differences
      found in BEC profiles between rats and mice and between ethanol administration
      paradigms may yield differences in the extent or mechanism of damage induced by
      ethanol, an important consideration when selecting an appropriate model for the
      investigation of ethanol-induced tissue damage.

PMID- 12798973
TI  - Cholecystokinin reduces ethanol consumption in golden hamsters.
AB  - In experimental conditions, golden hamsters (Mesocricetus auratus) avidly consume
      ethanol solutions. However, they are relatively resistant to the deleterious
      effects of ethanol even after months of continuous consumption, apparently
      because they metabolize ethanol rapidly and efficiently. Male hamsters with ad
      libitum access to food and water were presented with isocaloric solutions
      [weight/weight (wt./wt.)] of 10% ethanol and 17.75% glucose for 40-min periods on
      alternate days. When hamsters were injected with 0.9% saline before solution
      presentation the mean intake of ethanol solution (0.55 g) was about half that of
      glucose solution (1.08 g). Hamsters derived a mean of 0.36 g/kg/40 min of
      absolute ethanol from the ethanol solution, an amount that does not seem to
      exceed their metabolic capacity for ethanol. An intraperitoneal injection of a
      2.0-microg/kg dose of the C-terminal octapeptide of cholecystokinin (CCK-8)
      reduced intakes of both solutions by >50% if administered 5 min before solution
      presentation, but it was ineffectual if administered 45 min before presentation.
      When citric acid (2.5 g/l) was added to the glucose solution the baseline intakes
      of the two solutions were virtually equivalent, and when CCK-8 was administered
      over a range of doses (0.5-2.0 microg/kg) the intakes of the solutions did not
      differ significantly at any dose, supporting the suggestion that the
      pharmacological properties of ethanol play little or no role in mediating the
      consumption-inhibiting effect of exogenously administered cholecystokinin (CCK).
      Prior administration of lorglumide, a selective CCK type A receptor antagonist,
      completely attenuated the inhibitory effect of CCK-8. Findings are consistent
      with the notion that endogenous CCK plays a key role in the short-term control of
      ethanol intake in hamsters.

PMID- 12798974
TI  - No acute effect of red wine on the coagulation pathway in healthy men.
AB  - Binge drinking is associated with an increased risk of cardiovascular events.
      Those events often happen within hours after alcohol is consumed. Apart from
      arrhythmias and changes in blood pressure, these events may be caused by an acute
      (i.e., occurring within a 24-h period) shift of the hemostatic balance in a
      thrombogenic direction. Alcohol can influence platelet aggregation and inhibit
      fibrinolysis, but little is known about its direct effect on coagulation. In the
      current study, parameters of coagulation, reflecting either stimulation or
      inhibition, were measured 5 and 15 h after the consumption of four (62.5 g of
      alcohol) and eight (125 g of alcohol) glasses of red wine. Both doses had no
      direct effect on activated cephalin time, thrombin-antithrombin complexes,
      factors VII and VIII, and von Willebrand factor. In contrast with the observed
      effects on thrombocytes and fibrinolysis, the consumption of large amounts of
      wine does not influence the coagulation pathway.

PMID- 12798975
TI  - Neurosteroid secretion in panic disorder.
AB  - Evidence that neurosteroids have anxiolytic effects in animal models of anxiety
      has suggested that alterations of neurosteroid secretion might be implicated in
      the pathogenetic mechanisms of anxiety disorders in humans. In 25 female patients
      with panic disorder (PD) and 11 healthy female controls, we measured plasma
      concentrations of progesterone (PROG), pregnenolone (PREG), allopregnanolone
      (3alpha,5alpha-tetrahydroprogesterone=3alpha,5alpha-THPROG),
      dehydroepiandrosterone (DHEA) and tetrahydrodeoxycorticosterone (3alpha,5alpha
      THDOC) during a drug-free month and during the following month of paroxetine
      therapy. The neurosteroids were measured during the early follicular phase, the
      mid-luteal phase and the premenstrual phase of both months (days 7, 22 and 27
      from the beginning of the cycle). Significantly higher levels in patients than
      controls were found in PROG during the mid-luteal phase of both months, PREG in
      the premenstrual phase in the drug-free month, 3alpha,5alpha-THPROG during the
      follicular phase of the drug-free month and during the premenstrual phase of the
      therapy month, and 3alpha,5alpha-THDOC during the premenstrual phases of both
      months. DHEA levels did not differ in patients and controls. These results
      suggest that neurosteroids in PD are hypersecreted, possibly as an attempt to
      counteract the anxiogenic underlying hyperactivity of the hypothalamo-pituitary
      adrenal axis and to improve a reduced GABA(A) receptor sensitivity.

PMID- 12798976
TI  - A naturalistic visual scanning approach to assess selective attention in major
      depressive disorder.
AB  - Cognitive biases in information processing play an important role in the etiology
      and maintenance of emotional disorders. A new methodology to measure attentional
      biases is presented; this approach encourages subjects to scan and re-scan images
      with different thematic content, while the pattern of their attentional
      deployment is continuously monitored by an eye-tracking system. Measures of
      attentional bias are the total fixation time and the average glance duration on
      images belonging to a particular theme. Results showed that subjects with
      depressive disorder (n=8; Beck Depression Inventory Score>/=16) spent
      significantly more time looking at images with dysphoric themes than subjects in
      the control group (n=9). Correlation analysis revealed that the differences
      between the fixation times of the two groups are significantly correlated with
      the valence ratings, but not with the arousal ratings of the images. The average
      glance duration on images with social, neutral and threatening themes were
      similar for both groups, while the average glance duration on images with
      dysphoric themes was significantly larger for subjects with depressive disorder.
      The above results suggest that subjects with depressive disorder selectively
      attend to mood-congruent material and that depression appears to influence the
      elaborative stages of processing when dysphoric images are viewed.

PMID- 12798977
TI  - Plasma oxytocin in response to pharmaco-challenge to D-fenfluramine and placebo
      in healthy men.
AB  - The neuropeptide oxytocin is produced in the hypothalamus and released centrally
      and peripherally in response to serotonergic stimulation. Plasma oxytocin levels
      may be a candidate as a biological index of serotonergic function in response to
      pharmacological challenge by serotonergic agents. Fourteen male healthy subjects
      underwent a placebo challenge and a D-fenfluramine (D-FEN) (0.5 mg/kg) challenge
      on different days. Serial plasma oxytocin and prolactin levels were measured on
      each challenge day. D-FEN was associated with an increase in both oxytocin and
      prolactin. Plasma oxytocin may function as an index of central serotonin (5-HT)
      function in human subjects. Since oxytocin is released directly from limbic
      hypothalamic cells, this response presumably represents a direct central
      assessment of 5-HT response in limbic-hypothalamus. Further work will determine
      if the oxytocin response to 5-HT pharmaco-challenge, by virtue of its central
      origin, is more highly related to measures of psychopathology (e.g. aggression)
      than that of less central outcome parameters of 5-HT responsiveness (e.g.
      prolactin).

PMID- 12798978
TI  - Serum cholesterol and serotonergic function in major depressive disorder.
AB  - Studies have revealed a relationship between serum cholesterol levels and
      serotonergic (5HT) function in healthy young adults. Patients with major
      depressive disorder (MDD) may have significant differences in cholesterol levels
      compared with healthy adults, while MDD patients with elevated cholesterol have a
      poorer prognosis for treatment response. The goal of the present study is to
      examine (1) the relationship between serum cholesterol levels and central 5HT
      function by way of the cortisol and prolactin response to the 5HT-selective
      agonist DL-fenfluramine in MDD patients and (2) differences in 5HT-function
      between MDD patients who present with and without elevated cholesterol. Fasting
      serum cholesterol levels were measured in 21 outpatients with MDD. After oral
      administration of 60 mg of DL-fenfluramine in these patients, cortisol and
      prolactin responses were measured to test whether cholesterol levels predicted
      the degree of cortisol or prolactin response. Cortisol and prolactin responses
      were compared between patients with and without elevated cholesterol levels,
      defined as >/=200 mg/dl. MDD patients with elevated cholesterol levels were more
      likely to demonstrate an attenuated cortisol response. There was no relationship
      between cholesterol levels and cortisol or prolactin response. Excess cholesterol
      may adversely affect the function of membrane-bound serotonergic structures, and
      this may explain why MDD patients with elevated cholesterol are more likely to
      exhibit attenuated neuroendocrine responses, less likely to respond to treatment
      and more likely to relapse.

PMID- 12798979
TI  - Correlation between serum lipid, lipoprotein concentrations and anxious state,
      depressive state or major depressive disorder.
AB  - The purpose of this study was to investigate the correlation between serum lipid,
      lipoprotein concentrations and anxious state, depressive state or major
      depressive disorder. A total of 207 patients admitted for general health
      screening were recruited during a 1-year period. Using the Chinese Health
      Questionnaire, the Taiwanese Depression Questionnaire and the semi-structured
      clinical interview for DSM-IV, one psychiatrist screened all participants for the
      presence of anxiety or depressive disorders. Blood samples for serum lipid and
      lipoprotein concentrations and physical examination records were collected
      simultaneously. For patients who did not have systemic diseases (n=162), we found
      that high-density lipoprotein (HDL) cholesterol and the ratio of total
      cholesterol (TC)/HDL differed significantly among anxious state, depressive state
      and normal groups in men after age adjustment. On the other hand, the ratios of
      TC/HDL and low-density lipoprotein (LDL)/HDL showed significant differences
      between patients with major depressive disorder and normal controls in women.
      This study suggested that the level of HDL cholesterol and the ratios of TC/HDL
      and LDL/HDL (atherogenic index) might be another markers of the possible
      association between serum lipids and anxiety or depression.

PMID- 12798980
TI  - Blunted prolactin response to fentanyl in depression. Normalizing effect of
      partial sleep deprivation.
AB  - There is some evidence that sleep deprivation (SD) might exert its antidepressant
      properties by involving endogenous opioid mechanisms. The authors investigated
      the effects of mu-receptor agonist administration on prolactin release in
      depressed patients before and after partial SD. Medication-free female depressed
      inpatients (N=18) were participating in two fentanyl challenge tests after
      partial SD and undisturbed sleep, 3 days apart in random order. Healthy volunteer
      women (N=10) were enrolled after full night sleep as comparison subjects. Five of
      them had placebo trials. Participants were given an intravenous injection of 0.1
      mg/70 kg fentanyl at 9:00 AM. The prolactin secretory response to the opiate
      agonist was investigated for 1 h with serial blood sampling. After a night of
      undisturbed sleep, fentanyl administration prompted increases in plasma prolactin
      concentrations with blunted responses found in the depressed group. Following
      partial SD, the stimulated prolactin secretion of depressed patients increased
      significantly and was comparable to the response of comparison subjects. These
      findings suggest that SD acts via an opioid/dopamine-related mechanism. An
      alternative explanation, based on serotonin involvement is addressed in the
      discussion.

PMID- 12798981
TI  - Altered platelet serotonin 5-HT2A receptor density but not second messenger
      inositol trisphosphate levels in drug-free schizophrenic patients.
AB  - The 5-HT2A receptor binding parameters using [3H]ketanserine and its
      intracellular signal inositol 1,4,5 trisphosphate (IP3) concentrations were
      determined in platelets from schizophrenic patients so as to assess differences
      with respect to a control group and to a standardized antipsychotic drug
      treatment. Seventy-five antipsychotic-free patients with a DSM-IV diagnosis of
      paranoid schizophrenia were included in the study. Blood samples were collected
      before the onset of antipsychotic treatment (baseline values) and after 3 weeks
      of treatment. Antipsychotic-free schizophrenic patients showed significantly
      increased basal 5-HT2A densities in comparison to the control group, together
      with a significantly increase (23%) in the 5-HT2A binding density in those
      patients treated with risperidone. These changes could be attributed to an up
      regulation of 5-HT2A receptors caused by previous treatment with antipsychotic
      drugs, which is consistent with the chronic effect of 5-HT2A antagonists to up
      regulate the number of binding sites. With regard to second messenger IP3
      concentrations, basal concentrations in schizophrenic patients were not
      significantly different from control values, nor was there any significant
      difference between basal vs. posttreatment values. These results are possibly
      related to failure of second messenger systems of 'translating' extracellular
      messages generated presynaptically into effective neurotransmitter signals in
      schizophrenic patients.

PMID- 12798982
TI  - Platelet surface glycoprotein expression in post-stroke depression: a preliminary
      study.
AB  - Depression is a significant risk factor for and consequence of both
      cardiovascular disease and stroke. The pathophysiological processes underlying
      this association are poorly understood. This study utilised a technique for
      measurement of whole blood platelet surface glycoproteins involved in early
      adhesion and aggregation in sample populations of patients with depression and
      stroke, and healthy controls. We analysed the platelet surface glycoproteins GPIb
      and GPIIbIIIa using flow cytometry in eight depressed subjects (Hamilton
      depression score >17), 14 post-stroke subjects (seven depressed and seven non
      depressed), and in eight healthy control subjects. The number of GPIb receptors
      was significantly increased in subjects with depression and in post-stroke
      subjects compared to control subjects. The number of GPIb receptors from post
      stroke subjects was not significantly different from that of depressed subjects.
      There were no differences between any groups in measures of GPIIbIIIa receptor
      numbers. No additive effect of co-morbid depression on the surface expression
      level of either marker could be detected in the post-stroke subjects. Platelet
      dysfunction may be involved in the pathophysiological process underlying the
      association between depression and cerebrovascular disease.

PMID- 12798983
TI  - Axis III disorders in treatment-resistant major depressive disorder.
AB  - A number of naturalistic studies have found that medical co-morbidity conveys a
      worse long-term prognosis in the treatment of major depressive disorder (MDD).
      The purpose of this study was to test whether the presence of co-morbid medical
      conditions can predict clinical response in patients with treatment-resistant MDD
      (TRD) treated with open-label nortriptyline (NT). Ninety-two patients with TRD
      entered a 6-week open trial of NT. The presence of co-morbid medical disorders
      was assessed during the screen visit. The degree of medical co-morbidity during
      the screen visit was then quantified with the use of the Cumulative Illness
      Rating Scale-Geriatric Version (CIRS(G)). We tested whether CIRS(G) scores
      predicted clinical response or depression severity at endpoint. CIRS scores at
      baseline did not significantly predict treatment response. The results of this
      study fail to confirm the relationship between co-morbid medical conditions and
      poor outcome in the treatment of MDD for patients with TRD. Patients with TRD and
      co-morbid medical conditions can be expected to respond to antidepressants as
      well as their counterparts without concurrent axis III co-morbidity. The CIRS(G)
      scores for this TRD sample were lower than those reported for geriatric
      depression, or for depressed patients with severe medical illness, common in
      medical and surgical wards and in most specialty clinics of large academic
      centers. Thus, the present results cannot be generalized to such populations.

PMID- 12798984
TI  - Long-lasting cognitive impairment in unipolar major depression: a 6-month follow
      up study.
AB  - The aim of the study was to investigate cognitive impairment in major depression
      both acutely and after 6 months. All patients were investigated within a
      neurocognitive experimental setting at two testing sessions: at inclusion and
      after 6 months. Automatic and effortful information processing was investigated
      with a visual search paradigm. Twenty-one patients with recurrent major
      depression according to DSM-IV and a Hamilton Depression Rating Scale score >18
      were included in the study. Healthy subjects, matched for age and gender, were
      used as a control group. The results showed that the depressed patients performed
      equal to the control group on trials requiring automatic information processing
      at both sessions. However, the patients were impaired compared to the control
      group on trials requiring effortful information processing, also at both
      sessions. The depressed patients showed no improvement in cognitive performance
      from test 1 to test 2. The results indicate that the depressed patients had an
      impaired performance for effortful, but not automatic, visual search performance,
      and that the impairment remained after 6 months, despite significant improvement
      in their depression scores.

PMID- 12798985
TI  - Personality trait of behavioral inhibition is associated with oscillatory systems
      reciprocal relationships.
AB  - The main aim of this paper is to offer a speculative evolutionary based
      interpretation of brain oscillations. We suppose that delta, theta and alpha
      oscillations are informational channels of three hierarchical philogenetic
      systems. Delta oscillations are linked with the most ancient system, which was
      dominant in reptilian brain. Theta oscillations dominate in lower mammals. Alpha
      oscillations are manifestation of activity of the newest system, which dominate
      in adult humans. The three hierarchical phylogenetic systems fulfill parallel
      processing and their contribution to resulting behavior could differ in different
      individuals. Relative contribution of each system is regulated by means of
      descending inhibition (DI), higher systems inhibiting the lower. One of this
      theory's implications is that the personality trait of behavioral inhibition
      (behavioral inhibition system, BIS) should be associated with a stronger DI but
      particular mechanism could be different in children and adults. In order to test
      this hypothesis in 95 children (11-16 years) and 45 adults (18-37 years) resting
      EEG recordings were obtained along with BIS scores assessed by the Gray-Wilson
      Personality Questionnaire. Within subject strength of DI was measured by negative
      correlations between delta, theta and alpha powers estimated in individually
      adjusted EEG bands. In adults, BIS was associated with enhanced negative feedback
      from the alpha to the delta system, indicating a predominantly cortical origin of
      the adult humans' anxiety. In children, BIS was associated with enhanced negative
      relation between theta and delta systems, which is similar to the mechanism known
      in animals where limbic system plays the crucial role in mediating anxiety and
      fear. Although the presented empirical data partly supported the theory, it
      remains to be speculative and needs further empirical validation.

PMID- 12798986
TI  - Vagal influence on working memory and attention.
AB  - The aim of the present study was to investigate the effect of vagal tone on
      performance during executive and non-executive tasks, using a working memory and
      a sustained attention test. Reactivity to cognitive tasks was also investigated
      using heart rate (HR) and heart rate variability (HRV). Fifty-three male sailors
      from the Royal Norwegian Navy participated in this study. Inter-beat-intervals
      were recorded continuously for 5 min of baseline, followed by randomized
      presentation of a working memory test (WMT) based on Baddeley and Hitch's
      research (1974) and a continuous performance test (CPT). The session ended with a
      5-min recovery period. High HRV and low HRV groups were formed based on a median
      split of the root mean squared successive differences during baseline. The
      results showed that the high HRV group showed more correct responses than the low
      HRV group on the WMT. Furthermore, the high HRV group showed faster mean reaction
      time (mRT), more correct responses and less error, than the low HRV group on the
      CPT. Follow-up analysis revealed that this was evident only for components of the
      CPT where executive functions were involved. The analyses of reactivity showed a
      suppression of HRV and an increase in HR during presentation of cognitive tasks
      compared to recovery. This was evident for both groups. The present results
      indicated that high HRV was associated with better performance on tasks involving
      executive function.

PMID- 12798987
TI  - Somatosensory N250 and P300 during discrimination tasks.
AB  - We investigated the event-related potentials (N250 and P300) during three kinds
      of somatosensory discrimination tasks (oddball task). Strong (standard: 90%) and
      weak (deviant: 10%) electrical stimuli were randomly delivered to the right
      median nerve at the wrist with a 500-ms constant interstimulus interval. In a
      passive situation, subjects read a self-selected book, ignoring all stimuli
      (ignore condition). One of the active situations was a mental counting task
      (count condition), and another required pressing a button to deviant stimuli as
      quickly as possible (motor response condition). The N250-P300 complex was
      elicited by deviant stimuli in the active-attended situations, but not found in
      the ignore condition. The N250 peak amplitude was unchanged between the count and
      motor response conditions whereas P300 changed. In addition, the N250 latency
      significantly correlated with the reaction time, but the P300 latency did not.
      These results indicate that the somatosensory N250 reflects an attentive process
      which is related to the temporal aspect of behavioral response.

PMID- 12798988
TI  - Sex-related ERP differences in deviance detection.
AB  - The effect of sex on neural mechanisms of auditory mismatch detection was
      examined using dense sensor array (128 channel) event-related potential
      recordings (ERPs). ERPs of 32 right-handed subjects (16 males) were recorded to
      frequent (85%, 880 Hz) and infrequent (15%, 1480 Hz) tones. There were no sex
      differences in mismatch negativity (80-180 ms), however, the fronto-central P2
      (180-260 ms) was less positive in males (F=12.56, P<0.005) and the N2 (260-340
      ms) was more negative in males (F=6.28, P<0.05). The increased negativity in
      males spanning the P2 and N2 may index a top-down process of attention bias
      towards novelty. This result supports the hypothesis of an adaptive, sexually
      dimorphic processing of novel events in humans.

PMID- 12798989
TI  - Examination of normalized pulse volume-blood volume relationship: toward a more
      valid estimation of the finger sympathetic tone.
AB  - The pulsatile ac component (DeltaI) superimposed on the transmitted dc components
      (I: tissue plus blood) are obtained from a near-infrared finger
      photoplethysmogram using a wavelength of 810 nm. Only the dc component is given
      in an ischaemic circulatory state (I(t): tissue only). Based on Lambert-Beer's
      law, normalized pulse volume (NPV; =DeltaI/I) and blood volume [BV; =ln(I(t)/I)]
      have recently been advocated as quantitative measures. In this study, the NPV-BV
      relationship was examined using the finger occlusion method during rest and
      mental arithmetic in 16 female undergraduates. Finger vascular tone during stress
      was evaluated by the distance of the linear and parallel NPV-BV regression lines
      (D(NB)) between rest and stress conditions. A reference standard was provided by
      the linear regression lines of compliance index (CI=NPV/pulse pressure) and BV to
      the transmural pressure. The estimates at 40 mmHg of transmural pressure, as an
      arbitrarily chosen reference point, were calculated (CI40 and BV40). D(NB)
      correlated well with them (r=0.81 and 0.94, respectively). The multiple
      regression with mean blood pressure indicated that the combination of D(NB) and
      the reactivities in heart period could explain approximately 50% of valiance in
      pressor response. In conclusion, D(NB) is easily obtainable from the NPV-BV
      function and seems to be more specific and valid than NPV as an index of finger
      sympathetic tone, since it adjusts the mechanical effect of arterial distending
      pressure.

PMID- 12798990
TI  - Acute cardiovascular exercise and executive control function.
AB  - Acute cardiovascular exercise effects on cognitive function were examined using
      an executive control task by comparing neuroelectric and behavioral performance
      at baseline with post-exercise in 20 undergraduates. A within-subjects design was
      used to assess the P3 component of an event-related brain potential (ERP) and
      behavioral performance using a task that varied the amount of executive control
      required. The baseline session involved participation on the Eriksen flankers
      task followed by a graded maximal exercise test to measure cardiovascular
      fitness. The exercise session consisted of a 30-min acute bout of exercise on a
      treadmill followed by the Eriksen flankers task after heart rate returned to
      within 10% of pre-exercise levels. Across midline recordings sites, results
      indicated larger P3 amplitude following acute exercise compared to baseline.
      Shorter P3 latency was observed during the baseline Eriksen flankers task for the
      neutral compared to the incompatible condition; an effect not found following the
      acute bout of exercise. These findings suggest that acute bouts of cardiovascular
      exercise affect neuroelectric processes underlying executive control through the
      increased allocation of neuroelectric resources and through changes in cognitive
      processing and stimulus classification speed.

PMID- 12798991
TI  - Evaluating the quality of ERP measures across recording systems: a commentary on
      Debener et al. (2002).

PMID- 12798992
TI  - The VirE2 protein of Agrobacterium tumefaciens: the Yin and Yang of T-DNA
      transfer.
AB  - Agrobacterium tumefaciens has evolved a unique mechanism to solve the problem of
      transferring DNA across five bilayers; the inner and outer membranes of the
      bacterium, the plasma membrane of the plant cell and the double membrane formed
      by the nuclear envelope. The two first and two last seem to be mediated by,
      respectively, the type IV secretion system in Agrobacterium and the nuclear pore
      complex in the plant cell, but the mechanism by which the transferred DNA (T-DNA)
      crosses the plant membrane still remains a mystery. New biophysical experiments
      suggest that, in addition to its established role as a single-stranded DNA
      (ssDNA)-binding protein, the VirE2 protein forms a channel in the plant membrane
      allowing the passage of the T-DNA into the cell. Such a role would be reminiscent
      of translocator molecules secreted by the type III secretion system of pathogenic
      bacteria and inserting into the host eukaryotic plasma membrane. The implications
      for the structure of the protein, its regulation and role in vivo are discussed.

PMID- 12798993
TI  - Identification, cloning and characterization of rfaE of Actinobacillus
      pleuropneumoniae serotype 1, a gene involved in lipopolysaccharide inner-core
      biosynthesis.
AB  - Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia
      and its lipopolysaccharides (LPS) have been identified as important adhesins
      involved in adherence to host cells. To better understand the role of LPS core in
      the virulence of this organism, the aim of the present study was to identify and
      clone genes involved in LPS core biosynthesis by complementation with Salmonella
      enterica serovar Typhimurium mutants (rfaC, rfaD, rfaE and rfaF). Complementation
      with an A. pleuropneumoniae 4074 genomic library was successful with Salmonella
      mutant SL1102. This Salmonella deep-rough LPS mutant is defective for the rfaE
      gene, which is an ADP-heptose synthase. Novobiocin was used to select
      transformants that had the smooth-LPS type, since Salmonella strains with wild
      type smooth-LPS are less permeable, therefore more resistant to hydrophobic
      antibiotics like novobiocin. We obtained a clone that was able to restore the
      wild-type smooth-LPS Salmonella phenotype after complementation. The wild-type
      phenotype was confirmed using phage (Felix-O, P22c.2 and Ffm) susceptibility and
      SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). One of the
      open reading frames contained in the 3.3-kb insert in the plasmid encoded a 475
      amino-acid protein with 71% identity and 85% similarity to the RfaE protein of S.
      enterica. We then attempted to generate an A. pleuropneumoniae rfaE mutant by
      gene replacement. The rfaE gene seems essential in A. pleuropneumoniae viability
      as we were unable to isolate a heptose-less knockout mutant.

PMID- 12798994
TI  - Isolation of high molecular weight DNA from soil for cloning into BAC vectors.
AB  - Isolation of high molecular weight DNA fragments from soil, in excess of 1 Mb,
      and of sufficient quality for cloning into an Escherichia coli-streptomycete
      artificial chromosome vector is described. The combination of indirect extraction
      of cells, using a nycodenz extraction technique, followed by lysis of biomass
      immobilised in agarose plugs, allowed fragments in excess of 1 Mb to be purified.

PMID- 12798995
TI  - The Bacillus cereus bceT enterotoxin sequence reappraised.
AB  - Bacillus cereus is a known opportunistic human pathogen belonging to the B.
      cereus group. Establishment of the pathogenesis most likely involves several gene
      products. One of these gene products, a single gene component named bceT, has
      been cloned and described from B. cereus B-4ac [Agata et al., Microbiology 141
      (1995) 983-988]. However, our sequences of the bceT region from 16 B. cereus
      group strains showed inconsistency with the published bceT sequence. Only part of
      the bceT sequence had homology to our sequences. This initiated a more thorough
      investigation of the bceT sequence. Restriction site search and database searches
      intimated that the cloned bceT was created by an incidental joining of four DNA
      fragments during ligation. One of these fragments had 93% homology to an open
      reading frame (ORF 101) located within the pathogenic island of the Bacillus
      anthracis pXO1 virulence plasmid. We suggest that the reported enterotoxic
      activity of the original cloned bceT construct could be due to either the fusion
      gene or the fragment with homology to ORF 101 in pXO1.

PMID- 12798996
TI  - Membrane-derived oligosaccharides (MDOs) are essential for sodium dodecyl sulfate
      resistance in Escherichia coli.
AB  - We studied the role of membrane-derived oligosaccharides (MDOs) in sodium dodecyl
      sulfate (SDS) resistance by Escherichia coli. MDOs are also known as
      osmoregulated periplasmic glucans. Wild-type E. coli MC4100 grew in the presence
      of 10% SDS whereas isogenic mdoA and mdoB mutants could not grow above 0.5% SDS.
      Similarly, E. coli DF214, a mutant (pgi, zwf) unable to grow on glucose,
      exhibited conditional sensitivity to SDS in that it grew in gluconate and glucose
      or galactose but not in gluconate and mannose or sorbose. DF214 requires both
      gluconate and glucose/galactose because the gluconate is used for energy
      production, while glucose/galactose is used for MDO synthesis. Finally, the fate
      of E. coli cells subjected to SDS shock either during growth or when used as an
      inoculum is dependent on the presence or absence of sufficient MDOs. In both
      cases, cells grown under high-osmolarity (low-MDO) conditions were rapidly lysed
      by 5% SDS. Based on findings from a wild-type E. coli (MC4100), two mdo mutants
      and strain DF214 we conclude that MDOs are required for SDS resistance.

PMID- 12798997
TI  - Regulation of glnB gene promoter expression in Azospirillum brasilense by the
      NtrC protein.
AB  - In Azospirillum brasilense the glnB and glnA genes are clustered in an operon
      regulated by three different promoters: two located upstream of glnB (glnBp1
      sigma(70), and glnBp2-sigma(N)) and one as yet unidentified promoter, in the
      glnBA intergenic region. We have investigated the expression of the glnB gene
      promoter using glnB-lacZ gene fusions, mutation analysis, heterologous expression
      and DNA band-shift assays. Deletion of the glnB promoter region showed that NtrC
      binding sequences were essential for glnB expression under nitrogen limitation.
      The A. brasilense NtrC protein activated transcription of glnB-lacZ fusions in
      the heterologous genetic background of Escherichia coli. Expression of glnB-lacZ
      fusions in two A. brasilense ntrC mutants differed from that in the wild-type
      strain. In vitro studies also indicated that the purified NtrC protein from E.
      coli was able to bind to the glnB promoter region of A. brasilense. Our results
      show that the NtrC protein activates glnBglnA expression under nitrogen
      limitation in A. brasilense.

PMID- 12798998
TI  - Membrane filter (pore size, 0.22-0.45 micro m; thickness, 150 micro m) passing
      through activity of Pseudomonas aeruginosa and other bacterial species with
      indigenous infiltration ability.
AB  - Bacteria growing on MF-Millipore filters (thickness, 150 micro m) passed through
      the underlying membrane by their infiltration activity. Bacillus subtilis,
      Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli passed through
      a 0.45- micro m pore size filter within 48-96 h. Pseudomonas aeruginosa, Serratia
      marcescens, and Listeria monocytogenes passed through a 0.3- micro m pore size
      filter. P. aeruginosa passed through a 0.22- micro m pore size filter. The
      membranes which allowed passing-through of bacteria showed normal bubble point
      values in the integrity test. Studies with isogenic S. marcescens mutants
      indicated that flagellum-dependent motility or surface-active exolipid were
      important in the passing-through. P. aeruginosa PAO1 C strain defective in
      twitching motility was unable to pass through the 0.22- micro m filter. Scanning
      electron microscopy showed bacteria passing-through the 0.22- micro m filter.
      Millipore membrane filters having well-defined reticulate structures will be
      useful in the study of infiltration activity of microbes.

PMID- 12799000
TI  - Tetratricopeptide-like repeats in type-III-secretion chaperones and regulators.
AB  - Efficient type-III secretion depends on cytosolic molecular chaperones, which
      bind specifically to the translocators and effectors. In the past there has been
      a tendency to shoe-horn all type-III-secretion chaperones into a single
      structural and functional class. However, we have shown that the LcrH/SycD-like
      chaperones consist of three central tetratricopeptide-like repeats that are
      predicted to fold into an all-alpha-helical array that is quite distinct from the
      known structure of the SycE class of chaperones. Furthermore, we predict that
      this array creates a peptide-binding groove that is utterly different from the
      helix-binding groove in SycE. We present a homology model of LcrH/SycD that is
      consistent with existing mutagenesis data. We also report the existence of
      tetratricopeptide-like repeats in regulators of type-III secretion, such as HilA
      from Salmonella enterica and HrpB from Ralstonia solanacearum. The discovery of
      tetratricopeptide-like repeats in type-III-secretion regulators and chaperones
      provides a new conceptual framework for structural and mutagenesis studies and
      signals a potential unification of prokaryotic and eukaryotic chaperone biology.

PMID- 12798999
TI  - Detection and characterization of the Gloeosporium gloeosporioides growth
      inhibitory compound iturin A from Bacillus subtilis strain KS03.
AB  - The Bacillus subtilis strain KS03 was isolated, and identified as a biological
      control agent that inhibits the anthracnose disease fungus Gloeosporium
      gloeosporioides. The antifungal compound was purified from its culture broth
      through butanol extraction, diethylaminoethyl (DEAE) Sepharose CL-6B
      chromatography, and preparative thin layer chromatography. Tandem mass
      spectrometric analyses (MS/MS), with matrix-assisted laser desorption ionization
      (MALDI) time-of-fight/time-of-flight (TOF/TOF) mass spectrometry, showed that the
      antifungal compound was iturin A, a cyclic lipopeptide antibiotic. The major
      compound, with a molecular mass of 1042 Da, was identified as iturin A(2).

PMID- 12799001
TI  - Pulsed field gel electrophoresis of chromosomal DNA reveals a clonal population
      structure to Bacillus thuringiensis that relates in general to crystal protein
      gene content.
AB  - Seventy strains of Bacillus thuringiensis representing 21 serovars were allocated
      to 38 genomic groups using pulsed field gel electrophoresis (PFGE) of restriction
      enzyme-digested DNA. There was a broad correlation between PFGE type and serotype
      for serovars darmstadiensis, israelensis, kenyae, kumamotoensis, kurstaki, sotto,
      thuringiensis, and tolworthi, although some serovars included atypical strains.
      Serovars canadensis and entomocidus were heterogeneous. Detection of crystal
      protein genes by polymerase chain reaction indicated an approximate correlation
      between PFGE type and cry gene complement. For example, cry1 products were
      amplified from DNA from PFGE type 17 strains of serovar aizawai and from PFGE
      type 23 strains of serovar tolworthi but not from a PFGE 18 strain of aizawai nor
      from a PFGE type 24 strain of tolworthi. These data suggest a clonal population
      structure to B. thuringiensis with some consistency of Cry-plasmid composition
      within PFGE types.

PMID- 12799002
TI  - Regulation of the isofunctional genes ubiD and ubiX of the ubiquinone
      biosynthetic pathway of Escherichia coli.
AB  - The expressions of the isofunctional genes ubiD and ubiX of the ubiquinone
      biosynthetic pathway of Escherichia coli were compared under a variety of growth
      conditions and in several genetic backgrounds. LacZ operon fusions were
      constructed and were inserted in single copies into strain MC4100 and into its
      fnr, arcA or hemA carrying derivatives. During aerobic growth the expressions of
      both ubiD and ubiX depended on the carbon source: succinate>glycerol>glucose.
      Mutations in fnr, arcA or hemA increased the expressions of both genes. During
      anaerobic growth in LB medium glucose strongly inhibited the expression of ubiD
      but not of ubiX.

PMID- 12799003
TI  - Diversity of mercury resistance determinants among Bacillus strains isolated from
      sediment of Minamata Bay.
AB  - Thirty mercury-resistant (Hg R) Bacillus strains were isolated from mercury
      polluted sediment of Minamata Bay, Japan. Mercury resistance phenotypes were
      classified into broad-spectrum (resistant to inorganic Hg(2+) and
      organomercurials) and narrow-spectrum (resistant to inorganic Hg(2+) and
      sensitive to organomercurials) groups. Polymerase chain reaction (PCR) product
      sizes and the restriction nuclease site maps of mer operon regions from all broad
      spectrum Hg R Bacillus were identical to that of Bacillus megaterium MB1. On the
      other hand, the PCR products of the targeted merP (extracellular mercury-binding
      protein gene) and merA (intracellular mercury reductase protein gene) regions
      from the narrow-spectrum Hg R Bacillus were generally smaller than those of the
      B. megaterium MB1 mer determinant. Diversity of gene structure configurations was
      also observed by restriction fragment length polymorphism (RFLP) profiles of the
      merA PCR products from the narrow-spectrum Hg R Bacillus. The genetic diversity
      of narrow-spectrum mer operons was greater than that of broad-spectrum ones.

PMID- 12799004
TI  - Sugar metabolism in the extremely halophilic bacterium Salinibacter ruber.
AB  - Growth of Salinibacter ruber, a red, extremely halophilic bacterium
      phylogenetically affiliated with the Flavobacterium/Cytophaga branch of the
      domain Bacteria, is stimulated by a small number of sugars (glucose, maltose,
      starch at 1 g l(-1)). Glucose consumption starts after other substrates have been
      depleted. Glucose metabolism proceeds via a constitutive, salt-inhibited
      hexokinase and a constitutive salt-dependent nicotinamide adenine dinucleotide
      phosphate (NADP)-linked glucose-6-phosphate dehydrogenase. Glucose dehydrogenase
      and fructose-1,6-bisphosphate aldolase activity could not be detected. It is
      therefore suggested that Salinibacter metabolizes glucose by the classic Entner
      Doudoroff pathway and not by the Embden-Meyerhof glycolytic pathway or by the
      modified Entner-Doudoroff pathway present in halophilic Archaea of the family
      Halobacteriaceae, in which the phosphorylation step is postponed. However,
      activity of 2-keto-3-deoxy-6-phosphogluconate aldolase could not be detected in
      extracts of Salinibacter cells, whether or not grown in the presence of glucose.

PMID- 12799005
TI  - Induction of an adaptive tolerance response in the foodborne pathogen,
      Campylobacter jejuni.
AB  - In this study we aimed to determine if Campylobacter had the ability to induce an
      adaptive tolerance response (ATR) to acid and/or aerobic conditions.
      Campylobacter jejuni CI 120 was grown to the appropriate phase in Brucella broth
      under microaerobic conditions. Cells were initially adapted to a mild stress (pH
      5.5) for 5 h prior to challenge at pH 4.5, a lethal pH. Survival was examined by
      determining the numbers of viable cells on Campylobacter blood free selective
      agar base. Stationary phase cells adapted at pH 5.5 induced an ATR that enabled a
      100-fold greater survival compared to an uninduced culture. Aerobic adaptation
      also protected the cells against acid challenge. The cross protection provided a
      500-fold increase in survival when compared to unadapted cells. The incorporation
      of chloramphenicol during the induction period eliminated the ATR and resulted in
      death kinetics similar to an uninduced culture. These data suggest that
      Campylobacter spp. have the ability to induce an ATR to sublethal treatments,
      which increased their ability to withstand subsequent stresses.

PMID- 12799006
TI  - Use of bioluminescent Escherichia coli O157:H7 to study intra-protozoan survival
      of bacteria within Tetrahymena pyriformis.
AB  - A method was developed that enabled real-time monitoring of the uptake and
      survival of bioluminescent Escherichia coli O157 within the freshwater ciliate
      Tetrahymena pyriformis. Constitutively bioluminescent E. coli O157 pLITE27 was
      cocultured with T. pyriformis in nutrient-deficient (Chalkley's) and in nutrient
      rich (proteose peptone, yeast extract) media. Non-internalised bacteria were
      inactivated by addition of colistin, indicated by a decline in bioluminescence.
      Protozoa were subsequently lysed with Triton X-100 which lead to a further drop
      in bioluminescence, consistent with release of live internal bacteria from T.
      pyriformis into the colistin-containing environment. Bioluminescence measurements
      for non-lysed cultures indicated that internalised E. coli O157 pLITE27 cells
      were only slowly digested by T. pyriformis, in both media, over the time period
      studied. The results suggest that bioluminescent bacteria are useful tools in the
      study of bacterial intra-protozoan survival.

PMID- 12799007
TI  - Analysis of a DNA-binding motif of the Bacillus subtilis HrcA repressor protein.
AB  - The hrcA gene of Bacillus subtilis encodes a transcriptional repressor protein
      which negatively controls the heat shock operons dnaK and groESL. Alignment of
      the HrcA protein with repressor proteins from the NCBI database revealed that it
      exhibits a striking homology near its N-terminal part with proteins of the DeoR
      family. This region contains a helix-turn-helix motif and has been shown to be
      involved in DNA binding. To investigate whether this is also true for the HrcA
      protein, three critical amino acid residues were changed within or adjacent to
      the recognition helix. While single amino acid replacements barely influenced the
      binding activity, alteration of two consecutive amino acid residues within the
      recognition helix completely abolished the binding activity. When this mutant
      hrcA allele was expressed together with the wild-type allele within the same
      cell, it conferred a dominant-negative phenotype to the cells underlining that
      these amino acid residues are crucial for specific DNA binding and that HrcA
      binds to DNA in an oligomeric form.

PMID- 12799008
TI  - Oral bacteria resistant to mercury and to antibiotics are present in children
      with no previous exposure to amalgam restorative materials.
AB  - Dental plaque from 76 children without amalgam restorations was screened for
      bacteria resistant to mercuric chloride. Seventy-one per cent of the children
      harboured mercury-resistant oral bacteria and the median percentage of the total
      oral microflora resistant to mercuric chloride was 0.007% (range 0-5.3%). Eighty
      seven mercury-resistant bacteria were isolated and 86% of these were streptococci
      with Streptococcus mitis predominating. Sixty per cent of the mercury-resistant
      isolates were also resistant to at least one of the four antibiotics tested
      (penicillin, ampicillin, erythromycin and tetracycline) with resistance to
      tetracycline (40% of isolates) most frequently encountered.

PMID- 12799009
TI  - Design and development of a DNA array for rapid detection and identification of
      multiple tomato vascular wilt pathogens.
AB  - Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici, and Verticillium
      wilt, caused by either Verticillium albo-atrum or Verticillium dahliae, are
      devastating diseases of tomato (Lycopersicon esculentum) found worldwide.
      Monitoring is the cornerstone of integrated pest management of any disease. The
      lack of rapid, accurate, and reliable means by which plant pathogens can be
      detected and identified is one of the main limitations in integrated disease
      management. In this paper, we describe the development of a molecular detection
      system, based on DNA array technology, for rapid and efficient detection of these
      vascular wilt pathogens. We show the utility of this array for the sensitive
      detection of these pathogens from complex substrates like soil, plant tissues and
      irrigation water, and samples that are collected by tomato growers in their
      greenhouses.

PMID- 12799010
TI  - Purification and properties of an esterase from Aspergillus nomius HS-1 degrading
      ethylene glycol dibenzoate.
AB  - We isolated a fungal strain HS-1 utilizing either ethylene glycol dibenzoate or
      ethyl benzoate as sole source of carbon and energy, and identified it as
      Aspergillus nomius, based on morphological and rDNA analyses. An enzyme
      hydrolyzing the esters was purified from the culture supernatant of the strain to
      an electrophoretically homogeneous state. The enzyme was a carboxyl esterase with
      a monomeric structure, of which the molecular mass was about 60000, and inhibited
      by phenylmethylsulfonyl fluoride. The enzyme hydrolyzed various benzoate esters
      and p-nitrophenyl esters, and its hydrolysis rates for the most favorable
      substrates, n-butyl benzoate and p-nitrophenyl valerate, were comparable.

PMID- 12799011
TI  - A novel electrochemically active and Fe(III)-reducing bacterium phylogenetically
      related to Aeromonas hydrophila, isolated from a microbial fuel cell.
AB  - A facultative anaerobic bacterium was isolated from a mediator-less microbial
      fuel cell fed with artificial wastewater containing acetate and designated as
      PA3. The isolate was identified as a strain of Aeromonas hydrophila based on its
      biochemical, physiological and morphological characteristics as well as 16S rDNA
      sequence analysis and DNA-DNA hybridization. PA3 used glucose, glycerol, pyruvate
      and hydrogen to reduce Fe(III), nitrate and sulfate. Cyclic voltammetry showed
      that PA3 was electrochemically active and was the culture collection strain A.
      hydrophila KCTC 2358. Electricity was generated from a fuel cell-type reactor,
      the anode compartment of which was inoculated with cell suspensions of the
      isolate or A. hydrophila KCTC 2358. The electrochemical activities are novel
      characteristics of A. hydrophila.

PMID- 12799012
TI  - Expression of the red fluorescent protein DsRed-Express in filamentous ascomycete
      fungi.
AB  - The recently reported red fluorescent protein DsRed from the reef coral Discosoma
      sp. represents a new marker that has been codon-optimized for high expression in
      mammalian cells. To facilitate expression of DsRed in ascomycete fungi, we used
      the clone pDsRed-Express (Clontech) for constructing a plasmid vector, pPgpd
      DsRed, containing the constitutive Aspergillus nidulans glyceraldehyde 3
      phosphate (gpd) promoter. This vector was used for co-transformation of
      Penicillium paxilli, Trichoderma harzianum and Trichoderma virens (syn.
      Gliocladium virens) together with either pAN7-1 or gGFP, both containing a gene
      for hygromycin resistance for transformant selection. In addition, gGFP contains
      a green fluorescent protein (GFP) gene for expression in Ascomycetes. Expression
      of DsRed-Express was obtained in all three fungi, indicating that DsRed can be
      used as a highly effective vital marker in Ascomycetes. Dual marked transformants
      expressed both DsRed-Express and GFP in the same mycelium and were used for non
      quantitative comparison of the intensity of the fluorescence using confocal laser
      scanning microscopy.

PMID- 12799013
TI  - Severe reduction of superoxide dismutase activity in the yeast Saccharomyces
      cerevisae with the deletion or overexpression of GTS1.
AB  - We report herein that the level of reactive oxygen species (ROS) observed using
      dihydrorhodamine is much higher in either GTS1-deleted (gts1Delta) or GTS1
      overexpressing (TMpGTS1) transformants than in the wild-type and that the levels
      of protein carbonyls are increased and the glutathione levels are decreased in
      both transformants. Consistently, the activities of superoxide dismutases (SODs)
      in both gts1Delta and TMpGTS1 were severely weakened, while the protein levels of
      both Cu/Zn-SOD and Mn-SOD were not so changed. As the intracellular copper levels
      were significantly increased in both transformants, we hypothesized that, in
      either gts1Delta or TMpGTS1 cells, the imbalanced homeostasis of copper induced
      an accumulation of ROS which caused inactivation of SODs further increasing ROS
      levels.

PMID- 12799014
TI  - Genetic variation in myelin oligodendrocyte glycoprotein expression and
      susceptibility to experimental autoimmune encephalomyelitis.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is encoded within the RT1.M region of
      the rat MHC a susceptibility locus for MOG-induced experimental autoimmune
      encephalomyelitis (EAE). We report that the enhanced susceptibility of Brown
      Norway (BN) rats to MOG-EAE is associated with higher expression of MOG mRNA and
      protein in the nervous system than in the less susceptible Lewis (LEW) strain.
      MOG mRNA was also detected in the immune system, but there was no correlation
      with disease susceptibility. These results suggest that differences in the
      expression of MOG in the target organ, rather than in the immune system may
      influence susceptibility to MOG-EAE.

PMID- 12799015
TI  - Immune-modifying agents do not impair the survival, migration or proliferation of
      oligodendrocyte progenitors (CG-4) in vitro.
AB  - Limited intrinsic myelin repair occurs in multiple sclerosis (MS), mediated by
      oligodendrocyte progenitors that divide and migrate into demyelinated lesions.
      Experimental remyelination suggests that this repair restores function and may
      protect axons from subsequent degeneration. Immunomodulatory drugs such as
      corticosteroids, interferon-beta and azathioprine are widely used in MS. However,
      their influence on disease progression is modest, for reasons that are not fully
      explained. The direct effects of these drugs on remyelination biology remain
      relatively unexplored. We have investigated the effect of these MS therapies on
      oligodendrocyte progenitors to identify whether drug treatment might directly
      compromise repair, either therapeutic or spontaneous. None of these drugs
      affected CG-4 survival, migration or proliferation.

PMID- 12799016
TI  - Vav1-deficient mice are resistant to MOG-induced experimental autoimmune
      encephalomyelitis due to impaired antigen priming.
AB  - Mice that lack the guanine nucleotide exchange factor (GEF) Vav1 exhibit
      particular defects in antigen-triggered T cell activation but may have an
      autoreactive T cell repertoire due to impaired intra-thymic negative selection.
      MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) was used to
      test the susceptibility of Vav1(-/-) mice to organ-specific autoimmunity. Vav1(-/
      ) animals were found to be resistant to MOG(35-55)-EAE since the priming and in
      vivo expansion of myelin oligodendrocyte glycoprotein (MOG)-specific T cells was
      inefficient despite fully functional antigen presentation. Protection from cell
      mediated autoimmunity was not due to a Th2 bias, to the lack of IL-2 or a failure
      of Vav1(-/-) T cells in terms of chemotactic mobility.

PMID- 12799017
TI  - Bilirubin as a potent antioxidant suppresses experimental autoimmune
      encephalomyelitis: implications for the role of oxidative stress in the
      development of multiple sclerosis.
AB  - Increasing evidence shows that oxidative stress plays an important role in the
      pathogenesis of multiple sclerosis (MS) and its animal model, experimental
      autoimmune encephalomyelitis (EAE). In recent years, bilirubin has been
      demonstrated to be a potent antioxidant in vitro. In this study, we administered
      bilirubin to rats with acute and chronic EAE. Bilirubin prevented both acute and
      chronic EAE effectively. More significantly, bilirubin suppressed ongoing
      clinical EAE and halted EAE progression when given after disease onset.
      Subsequent histological examination showed that if administered to rats before
      the onset of EAE, bilirubin interfered with the invasion of inflammatory cells
      into the central nervous system (CNS) because it protected the blood-brain
      barrier (BBB) from free radical-induced permeability changes. However, in some
      cases, inflammation still occurred even when no clinical illness was observed. In
      rats with treatment initiated after the onset of EAE, despite the clinical
      improvements, treatment with bilirubin did not reduce the degree of CNS
      inflammation, or change cytokine expression in CNS lesions, indicating a lack of
      immunosuppressive effect of this treatment. By contrast, bilirubin treatment
      significantly alleviated oxidative damage in the spinal cord, and the clinical
      signs of EAE correlated well with the degree of oxidative injury in the lesions.
      Our results suggest that free radicals play an important role in the final
      effector stages of EAE, and that antioxidant therapies may have potential for the
      treatment of MS.

PMID- 12799018
TI  - IL-1Rrp2 expression and IL-1F9 (IL-1H1) actions in brain cells.
AB  - The recently discovered IL-1F9 (IL-1H1) is a putative member of the interleukin
      (IL)-1 family of cytokines that has been shown to activate nuclear factor-kappa B
      (NFkappaB) in Jurkat cells transfected with the orphan receptor IL-1 receptor
      related protein (IL-1Rrp)2. The aim of the present study was therefore to
      investigate expression of IL-1Rrp2 and to determine if IL-1F9 induces known IL-1
      signaling pathways in the different cell types of the mouse brain in culture.
      Messenger RNA for IL-1Rrp2 was not detected in primary neurones by RT-PCR, but
      significant constitutive expression was found in mixed glial cells, particularly
      in astrocytes and microglia, which was strongly decreased by exposure to
      bacterial lipopolysaccharide (LPS). LPS induced the release of IL-6, and
      activated NFkappaB and the mitogen-activated protein kinases (MAPKs) p38,
      extracellular signal-regulated protein kinase (ERK1/2) and c-Jun N-terminal
      kinase (JNK) in microglial cultures. IL-1beta induced release of IL-6 and
      activated NFkappaB, p38, JNK and ERK1/2 in mixed glial cultures, which was
      completely abolished in the presence of IL-1 receptor antagonist (IL-1ra). When
      injected intracerebroventrically in the rat, IL-1beta increased core body
      temperature, and reduced body weight and food intake. In contrast, IL-1F9 failed
      to induce any of these responses either in vivo or in vitro. These results
      demonstrate that glial cells may be a target for the new ligand IL-1F9, since
      high expression of IL-1Rrp2 mRNA was detected in these cells. However, IL-1F9
      failed to induce any of the classical IL-1beta responses, suggesting that it may
      trigger alternative pathway(s).

PMID- 12799019
TI  - Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous
      golli MBP knockout mice.
AB  - Increased golli MBP (golli) expression has been observed in the peripheral immune
      system of mice in the relapsing phase of EAE, raising the possibility that golli
      MBP expression in the periphery may contribute to relapses. Here we describe the
      generation of golli MBP-deficient mice and a comparison of the clinical course of
      EAE between heterozygous (golli(+/-)) and wild-type (golli(+/+)) mice. There was
      no difference between the two groups in incidence of disease, severity of the
      first episode of disease, or remission after the first episode. However, there
      was a significant reduction in relapses in golli(+/-) mice vs. controls,
      suggesting a role for golli proteins in the relapses in EAE.

PMID- 12799020
TI  - Interleukin-6, beta-amyloid peptide and NMDA interactions in rat cortical
      neurons.
AB  - Neuronal damage in Alzheimer's disease (AD) is thought to involve direct toxicity
      of beta-amyloid peptide (Abeta) and excitotoxicity involving NMDA receptors
      (NMDARs) and altered Ca(2+) dynamics. Inflammation agents produced by microglia
      or astrocytes and associated with senile plaques such as the cytokine interleukin
      6 (IL-6) could also contribute. To investigate this possibility, neuronal damage
      (lactate dehydrogenase assay, LDH, assay) was measured in cultures of rodent
      cortical neurons chronically treated with IL-6, Abeta or Abeta plus IL-6 and
      acutely treated with NMDA. Both Abeta and NMDA produced neuronal damage and this
      effect was larger with combined treatment. IL-6 did not produce significant
      neuronal damage but the largest neuronal damage was observed in cultures exposed
      to all three factors. IL-6 and Abeta enhanced Ca(2+) responses to NMDA and
      combined treatment produced the largest effect. These results are consistent with
      a role for interactions between Abeta, NMDA and IL-6 in the neuronal loss in AD.

PMID- 12799021
TI  - Kinetics of CCR7 expression differ between primary activation and effector memory
      states of T(H)1 and T(H)2 cells.
AB  - We explored the kinetics of CCR7 expression on T(H)1 and T(H)2 polarized cells as
      well as on antigen-specific T cell lines at various stages of differentiation. A
      striking pattern of early (days 7-14) inducible CCR7 expression was seen
      preferentially on primary T(H)1 cell lines, as compared to T(H)2 cells, and was
      dependent on the strength and duration of the T cell receptor signal. Upon
      repeated restimulation (days 21-28) and differentiation, a switch occurred in
      which T(H)2 cells had high CCR7 expression, whereas T(H)1 cells lost CCR7
      expression. Chronic (8 weeks and later) effector memory cell lines were 95% CCR7
      negative. These data demonstrate an ordered pattern of CCR7 expression that
      suggest more rapid priming of T(H)1 cells in the lymph node, and delayed priming
      with prolonged CCR7 expression during T(H)2 responses, and may have implications
      for tracking T(H)1 effector T cells ex vivo in autoimmune diseases.

PMID- 12799022
TI  - Autonomic function and autoantibodies to autonomic nervous tissues at follow-up
      in a cohort of young patients with type 1 diabetes. Effects of serum from
      diabetic patients on human adrenergic cells.
AB  - Recent studies have linked autoimmunity to nervous tissue structures and diabetic
      autonomic neuropathy. To evaluate prospectively the early stage of type 1
      diabetes and the natural history of this association, we monitored the autonomic
      function and the presence of autoantibodies (Ab) to sympathetic and
      parasympathetic nervous structures in a cohort of 92 diabetic adolescent
      patients, recruited and followed-up after 40+/-3 months. The presence of
      circulating Ab and their ability to activate complement was also assessed using a
      human adrenergic neuroblastoma cell line, and the effect of patients' sera on
      these cells was evaluated by different methods assessing cytotoxic effects and
      apoptosis. Thirty-nine percent of the Ab-positive patients had one abnormal test
      (p=0.07 vs. Ab-negative patients). Serum from four patients positive for anti
      cervical ganglia Ab showed positive staining of neuroblastoma cells and displayed
      ability to activate complement. Serum from two adolescent patients with anti
      cervical ganglia and anti-neuroblastoma cells Ab, induced cytotoxic effects and
      damaged the plasma membrane of the neuroblastoma cells. Moreover, sera from two
      adult patients with overt autonomic neuropathy, used as positive controls,
      induced apoptosis of these cells, assessed by TUNEL. Our data indicate that
      symptomatic autonomic neuropathy is not characteristic of young diabetic
      patients, but that autoantibodies to autonomic structures are present and persist
      in the first 20 years of disease, possibly associated with subtle autonomic
      dysfunction and cytotoxic effect on sympathetic cells.

PMID- 12799023
TI  - Antibodies to sulfatide in cerebrospinal fluid of patients with multiple
      sclerosis.
AB  - The identity of target antigen(s) in multiple sclerosis (MS) remains elusive
      despite much effort to identify it. We analyzed cerebrospinal fluid (CSF) from
      patients with MS, other neurological diseases (OND), other diseases (OD) and
      healthy controls for antibodies against purified sulfatide, a major
      glycosphingolipid of human myelin, by an enzyme-linked immunosorbent assay
      (ELISA) and a thin-layer chromatogram (TLC)-immunostaining technique. Elevated
      anti-sulfatide antibodies were significantly higher in MS patients as compared
      with the OND group (p<0.05) and all controls combined (P<0.025). Binding of high
      titer antibodies to sulfatide was confirmed with TLC-immunostaining. Anti
      sulfatide antibodies were detected in all subtypes of MS although the frequency
      was higher in patients with secondary progressive MS (SPMS) than in patients with
      primary progressive (PPMS) and relapsing-remitting MS (RRMS). The data
      demonstrate a humoral response to sulfatide in the CSF of patients with MS.

PMID- 12799024
TI  - Interleukin-10 promoter polymorphisms in patients with Guillain-Barre syndrome.
AB  - Interleukin-10 (IL-10) may have both pro- and anti-inflammatory effects in
      Guillain-Barre syndrome (GBS). The distribution of polymorphisms in the IL-10
      gene (-1082 (G/A), -819 (T/C) and -592 (A/C)) was analysed to determine whether
      they could influence disease susceptibility or clinical course in GBS. The -592
      CC and -819 CC genotypes associated with increased IL-10 response were more
      frequent in the GBS patients than in the controls (P=0.027), but the
      polymorphisms did not influence the clinical course of the disease.

PMID- 12799026
TI  - An early and sustained peripheral inflammatory response in acute ischaemic
      stroke: relationships with infection and atherosclerosis.
AB  - Central nervous system and peripheral inflammation is important in the responses
      to ischaemic stroke, and may also predispose to its development. We aimed to
      identify (1) the extent to which a peripheral inflammatory response is activated
      in patients following acute stroke, and (2) whether there was evidence for
      preexisting peripheral inflammation. Thirty-six patients with ischaemic stroke
      within 12 h of onset of symptoms had serial blood samples taken up to 12 months
      for analysis of markers of inflammation. Thirty-six control subjects,
      individually matched for age, sex and degree of atherosclerosis, were also
      studied. Median C-reactive protein (CRP) was elevated, relative to controls (2.08
      mg/l), from admission (4.31 mg/l) (p</=0.001) until 3 months (2.90 mg/l)
      (p</=0.01), the greatest elevation occurring at 5-7 days (17.67 mg/l)
      (p</=0.001). Elevations were also seen in erythrocyte sedimentation rate (ESR)
      and white blood cell (WBC) count until 3 months. Median plasma IL-6 was also
      elevated, relative to controls (9 pg/ml), by 24 h after onset of symptoms (22
      pg/ml) (p</=0.01), and remained elevated at 5-7 days (23 pg/ml) (p</=0.01), but
      not at 3 months. Less marked elevations in these markers were seen in patients
      without evidence of infection except for IL-6, which was not increased in the
      absence of infection. These data provide evidence of an early and sustained
      peripheral inflammatory response to acute ischaemic stroke in patients with or
      without evidence of infection. The very early increase in concentrations of
      inflammatory markers after stroke may either be induced by stroke itself, or may
      indicate a preexisting inflammatory condition in stroke patients which may
      contribute to the development of stroke.

PMID- 12799027
TI  - Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on
      the IFN-gamma responses of healthy CD4+ T cells.
AB  - In humans, interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) normally favor
      IFN-gamma-producing "Th1" T cell responses. Myasthenia gravis (MG) patients with
      thymomas frequently have high-titer neutralizing autoantibodies against these
      cytokines, but not against IFN-gamma. Because they occasionally develop
      intractable (even fatal) infections, we have tested effects of their sera on the
      generation of IFN-gamma responses by healthy adult T cells to autologous
      lipopolysaccharide (LPS)-treated dendritic cells (DC). Anti-IL-12(+) sera
      consistently reduced IFN-gamma responses substantially, whether assessed by
      intracellular staining or ELISA. Therefore, thymoma patients with intractable
      infections might benefit from cautious IFN-gamma therapy. We discuss wider
      implications of the surprising rarity of clear clinical hazards-or benefits-of
      these autoantibodies.

PMID- 12799025
TI  - Dynamics of immune cell trafficking in interferon-beta treated multiple sclerosis
      patients.
AB  - PURPOSE: To investigate the effects of interferon-beta-1a (IFN-beta-1a) on the
      trafficking of cell populations in peripheral blood cells of multiple sclerosis
      (MS) patients. METHODS: In this open-label pharmacodynamic study, peripheral
      blood was obtained from 10 relapsing-remitting (RR) MS patients just prior to and
      at 1, 2, 4, 8, 24, 48, 120, and 168 h after intramuscular injection of 30-microg
      IFN-beta-1a. Timed samples were also obtained from five controls at 0, 8, 24, 48
      and 168 h. The blood cells were analyzed using four-color flow cytometry with
      antibody conjugates directed against cell surface proteins specific for T cells,
      B cells, NK cells, and the activation marker, CD69. RESULTS: IFN-beta-1a
      treatment resulted in selective, time-dependent effects on many cell populations
      in peripheral blood. The trafficking of T-helper and T-suppressor/cytotoxic
      subsets of T cells were qualitatively different. The most prominent effects were
      on the trafficking of natural killer cells, the levels of which decreased to
      23.5% of pretreatment values at 8 h after treatment. The levels of CD69-positive
      NK cells increased to a peak value of 606% of pretreatment levels at the 24-h
      time point. In untreated controls, these characteristic trafficking effects were
      not observed. There was inter-patient heterogeneity in the levels of activated NK
      cells at the 6-month time point that may potentially be relevant for
      individualizing IFN-beta therapy. CONCLUSIONS: IFN-beta treatment can induce
      specific, selective, and time-dependent trafficking of cells and its effects on
      different subsets of a given cell type are not qualitatively similar. The
      dynamics indicate that the activation of NK cells by IFN-beta is possibly
      dependent on the trafficking of NK cells. The activated NK cell levels after
      prolonged therapy may potentially provide a surrogate marker for IFN-beta
      exposure.

PMID- 12799029
TI  - Study of Herpesvirus saimiri immortalization of gammadelta T cells derived from
      peripheral blood and CSF of multiple sclerosis patients.
AB  - Human gammadelta T cells are an integral part of the innate immune system and
      have been difficult to study owing primarily to their relatively low abundance
      and their fastidious culture properties associated with short in vitro lifespan.
      Their increased presence within multiple sclerosis (MS) white matter plaques
      compared to peripheral blood (PB) suggests a specific interaction with central
      nervous system (CNS) tissues. This fact, together with their innate ability to
      lyse human oligodendrocytes in culture implicate them possibly in the
      pathogenesis of MS. To further investigate their potential role in MS, we studied
      whether gammadelta T cells could be effectively immortalized using Herpesvirus
      saimiri (HVS), so that they could be studied in longer-term cultures. Effective
      culture conditions were established resulting in efficient HVS growth
      transformation of multiple PB and CSF gammadelta T cell lines and clones that
      could exist in IL-2-dependent culture for periods in excess of 2 years.
      Phenotypic and functional comparison studies with parental nontransformed
      gammadelta T cells were performed to characterize the changes that possibly
      induced by viral transformation. Using panels of transformed gammadelta T cell
      clones representing discrete gammadelta TcR subtypes, there was no apparent
      correlation between intracytoplasmic cytokine expression or tumor cell
      cytotoxicity with a specific TcR. All transformed gammadelta T cells analyzed,
      regardless of their compartment of origin, strongly expressed intracytoplasmic
      IFN-gamma and TNF-alpha, but little IL-2 or anti-inflammatory IL-4 or IL-10.
      These results indicate that HVS transformation of gammadelta T cells can be used
      to generate lines and clones from both the CSF and PB compartments for further
      study and elucidation of their potential role in MS pathogenesis.

PMID- 12799028
TI  - Microarray analysis identifies interferon beta-regulated genes in multiple
      sclerosis.
AB  - The molecular mechanisms for the interferon beta (IFNbeta) treatment of multiple
      sclerosis (MS) remain to be characterized. Using cDNA microarray technology, we
      have compared the gene expression profile of T and non-T cells derived from
      relapsing-remitting MS before and after treatment with IFNbeta-1b. IFNbeta
      treatment significantly altered expression of 21 genes out of 1263 at 3 and 6
      months after treatment. These genes included nine with IFN-responsive promoter
      elements. Whereas there was no change in Th1 or Th2 marker genes, some of the
      changes were unexpected but coincided with the beneficial effect of IFNbeta in
      MS.

PMID- 12799030
TI  - Effects on axonal conduction of anti-ganglioside sera and sera from patients with
      Guillain-Barre syndrome.
AB  - The efficacy of plasma exchange as a therapy for Guillain-Barre syndrome (GBS)
      suggests that humoral factors might contribute to the axonal conduction block
      responsible for the major symptoms of the disease. To explore this possibility,
      we have applied sera to rat spinal roots in vitro while monitoring axonal
      conduction. Neither fresh sera from 12 patients with GBS or Miller-Fisher
      syndrome (MFS), nor serum from rabbits immunised with Campylobacter jejuni from
      patients with GBS, MFS or gastroenteritis were effective in causing acute
      conduction block, despite the presence of antibodies to gangliosides GD3, GM1,
      GQ1b and GT1a. Potential explanations are advanced.

PMID- 12799031
TI  - GM1 antibodies in post-polio syndrome and previous paralytic polio.
AB  - We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies,
      since such antibodies have been associated with PPS and motor neuron disorders.
      Sera from 144 patients with previous poliomyelitis (105 paralytic, 22
      nonparalytic and 17 PPS), 60 with previous Guillain-Barre syndrome, 44 with
      amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed
      with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in
      14% of the PPS patients, but the prevalence did not differ significantly from
      that of the other groups. Our study does not support the hypothesis that GM1
      antibodies are involved in the pathogenesis of PPS.

PMID- 12799032
TI  - Evidence for endogenous interleukin-10 during nociception.
AB  - Cytokines such as IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) have
      been shown to contribute directly to central and peripheral neuropathic pain.
      Recently, exogenous interleukin-10 (IL-10) was shown to impede development of
      dynorphin-induced allodynia presumably by inhibiting IL-1beta. We therefore
      wanted to determine whether endogenous IL-10 had a role in pain perception. By
      measuring the latency of the paw licking response, we show in IL-10 knockout mice
      and in normal mice treated with anti-IL-10 that latency times are increased,
      suggesting that endogenous IL-10 increases nociception. This does not appear to
      be directly correlated with IL-10's regulation of DREAM, a transcriptional
      regulator of prodynorphin synthesis.

PMID- 12799033
TI  - Leptin as a marker of multiple sclerosis activity in patients treated with
      interferon-beta.
AB  - The role of leptin was investigated in relapsing-remitting multiple sclerosis
      (MS). Control and MS patients showed comparable baseline serum leptin levels.
      During the first year of IFNbeta-1a treatment, leptin significantly decreased
      since 2 months after starting therapy in 11 patients who had no relapses. A
      significant decrease in IL12/IL10 ratio was observed in this group of patients
      only after 1 year of treatment. An increase of leptin was observed before the
      first clinical exacerbation in 13 relapsing patients. Leptin may play a
      pathogenic role in MS and can be a useful marker of disease activity and response
      to therapy.

PMID- 12799034
TI  - Interferon beta promotes survival in primary astrocytes through
      phosphatidylinositol 3-kinase.
AB  - Although interferon-beta (IFN-beta) has been demonstrated to be effective in the
      treatment of multiple sclerosis (MS) patients, the mechanism(s) underlying its
      beneficial effects has not been uncovered yet. Until now, most of the effort in
      the study of the relevant mechanisms of IFN-beta has dealt with its ability to
      modulate the immune response. Only recently, it has been proposed that the
      beneficial effects of IFN-beta in MS patients could depend on its ability to
      modulate astrocyte function. In the present work, we have found that IFN-beta
      treatment promotes the survival of astrocytes through stimulation of the
      phosphatidylinositol 3-kinase (PI-3K)/Akt pathway. We propose that the beneficial
      effects of IFN-beta in MS therapy may depend, at least in part, on its capacity
      to protect astrocytes against the apoptotic cell death that occurs in the early
      steps of the pathogenesis of MS.

PMID- 12799035
TI  - Antigen loading of dendritic cells with whole tumor cell preparations.
AB  - Dendritic cells (DC) based vaccinations have been widely used for the induction
      of anti-tumoral immunity in clinical studies. Antigen loading of DC with whole
      tumor cell preparations is an attractive method whenever tumor cell material is
      available. In order to determine parameters for the loading procedure, we
      performed dose finding and timing experiments. We found that apoptotic and
      necrotic melanoma cells up to a ratio of one-to-one, equivalent to 1mg/ml protein
      per 1 x 10(6) DC, can be added to monocyte derived DC without effecting DC
      recovery extensively. Using the isolated protein content of tumor cells (lysate)
      as a parameter, up to 5 mg/ml protein per 1 x 10(6) DC can be added. To achieve
      significant protein uptake at least 1 mg/ml of protein have to be added for more
      than 24 h as tested with FITC-labelled ovalbumin. Maturation inducing cytokines
      can be added simultaneously with the tumor cell preparations to immature DC
      without affecting the uptake. Furthermore, we tested the feasibility of
      cryopreservation of loaded and matured DC to facilitate the generation of ready
      to use aliquots. DC were cryopreserved in a mix of human serum albumin, DMSO and
      5% glucose. After thawing, surface expression of molecules indicating the mature
      status (CD83, costimulatory and MHC molecules), was found to be unaltered.
      Furthermore, cryopreserved DC kept the capability to stimulate allogenic T-cell
      proliferation in mixed leukocyte reactions at full level. Loaded and matured DC
      pulsed with influenza matrix peptide (IMP) retained the capacity to induce the
      generation of IMP-specific cytotoxic T-lymphocytes after cryopreservation as
      measured by ELISPOT and tetramer staining. The expression of the chemokine
      receptor CXCR-4 and CCR-7 remained unaltered during cryopreservation and the
      migratory responsiveness towards MIP-3beta was unaltered as measured in a
      migration assay. Thus we conclude that the large scale loading and maturation of
      DC with whole tumor cell preparations can be performed in a single session. These
      data will facilitate the clinical application of DC loaded with whole tumor cell
      preparations.

PMID- 12799036
TI  - Development and evaluation of a flow-cytometric assay of specific cell-mediated
      immune response in activated whole blood for the detection of cell-mediated
      immunity against varicella-zoster virus.
AB  - A new assay for the detection of specific cell-mediated immune (CMI) responses is
      described. Whole blood, diluted 1/10 in medium, was cultured in the presence or
      the absence of specific antigens. Results were assessed by flow cytometric
      analysis with or without immunophenotyping to detect proliferating lymphoblasts
      among cultured cells. Interferon-gamma, IL-10, and IL-5 in culture supernatants
      are measured by ELISAs. The assay was evaluated using samples from 37 VZV
      antibody-positive children with a history of chickenpox and samples from 15
      seronegative children without a history of chickenpox; it displayed a sensitivity
      of 95% and a specificity of 100% for the detection of varicella-zoster virus
      (VZV)-specific CMI. The intraassay and interassay variations of the new test were
      lower than with the conventional assay for CMI, detecting thymidine incorporation
      in peripheral blood mononuclear cells (PBMCs). Cytokines were detected in only
      70% of cultures from VZV-antibody-positive subjects. The cytokine response was
      restricted to IFN-gamma in most cases. The Flow-cytometric Assay of Specific Cell
      mediated Immune response in Activated whole blood (FASCIA) is a precise and
      accurate yet simple and convenient test that can be readily employed for the
      examination of single samples as well as for large-scale studies.

PMID- 12799037
TI  - Quantification of UVR-induced DNA damage: global- versus gene-specific levels of
      thymine dimers.
AB  - The induction and repair of DNA damage has been shown to occur heterogeneously
      throughout the mammalian genome. As a consequence, analysis of these parameters
      at a global genome level may not reflect important gene-level events. Few
      techniques have been established to explore quantitatively gene-specific DNA
      damage and repair. Most of these are polymerase chain reaction (PCR)-based assays
      and are relatively insensitive, relying on decreased PCR amplification arising
      from damage in template DNA. We have developed a quantitative assay that combines
      specific immunocapture of damaged DNA by an antiserum specific for thymine dimers
      (IgG479), with PCR amplification of a 149 bp fragment of the human H-ras proto
      oncogene. Quantification of DNA damage was based upon proportionality between the
      amount of the PCR product and the initial amount of damage. Detection of thymine
      dimers was possible with nanogram amounts of genomic DNA and increased in a
      linear, dose-responsive manner. Using this assay, gene-level induction of thymine
      dimers was shown to be directly proportional to levels induced in the global
      genome of ultraviolet radiation (UVR)-exposed, extracted DNA as measured by gas
      chromatography-mass spectrometry (GC-MS). This result suggests that global damage
      assessments do indeed reflect gene-level events although we predict that this
      relationship may not be maintained when applied to a cellular system. These
      findings demonstrate the suitability of this approach to the detection of UVR
      induced DNA damage at the level of individual genes.

PMID- 12799038
TI  - Simultaneous monitoring of binding to and activation of tumor-specific T
      lymphocytes by peptide-MHC.
AB  - The recent advent of peptide-MHC tetramers has provided a new and effective tool
      for studying antigen-specific T cell populations through monitoring tetramer
      binding to T cells by flow cytometry. Yet information regarding T cell activation
      induced by the bound tetramers cannot be deduced from binding studies alone;
      complementary methods are needed to bridge this gap. To this end, we have
      developed a new approach that now enables monitoring both binding to and
      activation of T cells by peptide-MHC tetramers at the single-cell level. For this
      purpose, we have employed the CellScan, a non-flow cytometer designed for
      repetitive measurements of optical parameters (e.g., fluorescence intensity and
      polarization) of individual living cells. A melanoma-specific MART1 CTL line and
      a gp100-specific CTL clone were incubated with specific and control single-chain
      peptide-MHC tetramers for 45 min. Subsequently, the fluorescence intensity and
      polarization were measured by the CellScan. Specific binding of fluorescently
      labeled peptide-MHC tetramers to CTLs, recorded by the CellScan, was comparable
      to that measured by flow cytometry. CellScan monitoring of the degree of
      fluorescence polarization of fluorescein diacetate-labeled CTLs that were reacted
      with tetramers revealed specific activation of the CTLs, which was confirmed by
      cytokine (INF gamma) production. These results provide a new means of monitoring
      both the binding to and activation of T lymphocytes by cognate peptide-MHC
      complexes at the single-cell level, which can now be applied to distinguish
      between cognate responding and anergic T cells.

PMID- 12799039
TI  - Determination of the eicosanoid response to inflammatory stimuli in whole blood
      and its pharmacological modulation ex vivo.
AB  - Recognition of pathogens by immune cells initiates the release of numerous
      signaling molecules, including cytokines and eicosanoids. Here, we describe a
      simple procedure by which eicosanoids such as prostaglandin E(2) (PGE(2)),
      leukotriene B(4) (LTB(4)) and thromboxane B(2) (TxB(2)) can be measured using
      commercial enzyme immunoassays (EIAs) in the supernatant of whole blood
      stimulated with inflammatory stimuli. This is illustrated for numerous stimuli.
      The kinetics by which lipopolysaccharide (LPS) induces cyclooxygenase (COX)-2
      expression in this setup were determined by quantitative reverse transcription
      polymerase chain reaction (RT-PCR). The eicosanoid response of the blood of 160
      healthy volunteers to 1 microg/ml LPS was measured. To determine whether the
      action of a drug in vivo is represented ex vivo in the eicosanoid response of
      blood, one volunteer took a standard dose of a number of commercially available
      cyclooxygenase inhibitors on different days and the eicosanoid response of his
      blood to LPS was determined before ingestion as well as 2 and 6 h afterwards. The
      efficacy of the different pharmaceuticals on cyclooxygenase but not lipoxygenase
      products or cytokines could be monitored ex vivo. Similarly, ex vivo eicosanoid
      release was measured in blood from 10 volunteers who had taken 50 mg
      flurbiprofen. The method described extends approaches for studying whole blood
      cytokine release to the lipid mediators formed from arachidonic acid. These
      important signaling molecules represent targets for pharmacological intervention,
      which can now be monitored in vitro, as well as ex vivo employing the same model.
      Furthermore, the assay could be used to characterize the immune status of patient
      groups or to monitor the course of disease.

PMID- 12799040
TI  - Lymphocyte subset enumeration in HIV seronegative and HIV-1 seropositive adults
      in Dar es Salaam, Tanzania: determination of reference values in males and
      females and comparison of two flow cytometric methods.
AB  - The level of CD4(+) T-lymphocytes represents a useful marker with which to
      monitor the progression of HIV infection. Sex and geographical differences in the
      reference values of lymphocyte subsets have been reported. We have compared two
      flow cytometric methods (MultiSET and SimulSET) for the quantification of
      lymphocyte subsets using whole blood from 92 HIV seropositive and 241
      seronegative adults, and determined the reference values of lymphocyte subsets in
      HIV seronegative Tanzanian subjects. In seronegative Tanzanian subjects, the
      percentages of CD3(+) and CD4(+) T-lymphocytes and the CD4(+):CD8(+) T-lymphocyte
      ratios were lower while the percentage of natural killer cells was higher
      compared to the levels of the corresponding parameters reported for Europeans.
      Seronegative Tanzanian females had significantly higher levels of CD3(+) and
      CD4(+) T-lymphocytes and CD4(+):CD8(+) T-lymphocyte ratios compared to
      seronegative males. The correlation coefficients of CD3(+), CD4(+) and CD8(+) T
      lymphocyte counts and percentages obtained by the two flow cytometric methods
      were high. The median values of the number of CD4(+) T-lymphocytes obtained by
      the two methods were not significantly different. In conclusion, determination of
      the reference values of lymphocyte subsets in HIV seronegative Tanzanian adults
      showed significant sex differences and differences in percentage values compared
      to those reported in certain other geographical areas. There was acceptable
      agreement in the levels of CD4(+) T-lymphocyte values obtained by the two flow
      cytometric methods.

PMID- 12799041
TI  - Soluble HIV-specific T cell receptor: expression, purification and analysis of
      the specificity.
AB  - We have produced soluble T cell receptor (TCR) derived from a human CD8(+)
      cytotoxic T lymphocyte (CTL) clone D3 that recognizes the immunodominant HIV Gag
      peptide SLYNTVATL (SL9) in association with major histocompatibility complex
      (MHC) class I protein HLA-A2. Drosophila Schneider cells (S2) were used to
      express genes coding the TCR alpha and beta chains under an inducible promoter.
      Both chains were labeled with two different tags: a (His)(6) was introduced at
      the C-terminal end of alpha chain, while beta chain was terminated by c-myc.
      Since an isolated alpha chain is unstable unless it is associated with a beta
      chain, this design permits rapid separation of alpha,beta-heterodimer from
      unpaired beta chain in a single step of Ni-NTA Agarose chromatography yielding
      90% pure alpha,beta-TCR. Introduction of the c-myc epitope to the beta chain
      allows capture of soluble D3 from the culture supernatant by immobilized anti-c
      myc antibody, without the need for receptor purification. The TCR specificity was
      then examined by analyzing the binding of peptide-HLA-A2/tetramer in an ELISA
      assay. Using this assay, we have also evaluated the binding of monomeric SL9-HLA
      A2 complex to the immobilized D3 TCR and determined that the affinity measurement
      of the D3-SL9-HLA-A2 reaction is similar to that obtained by a biosensor
      instrument. We propose that the approach described here is generally useful for
      purification of other soluble TCRs and will allow rapid analysis of their
      specificity.

PMID- 12799042
TI  - Development of a quantitative antigen-specific cell-based ELISA for the 7G7/B6
      monoclonal antibody directed toward IL-2Ralpha.
AB  - Interleukin-2 receptor alpha (IL-2Ralpha, CD25) has been identified as a valuable
      target for immunotherapy. The 7G7/B6 monoclonal antibody, a mouse IgG2a kappa,
      recognizes an epitope of the IL-2Ralpha peptide, other than that identified by
      anti-Tac. This antibody is currently being explored for potential therapeutic and
      diagnostic applications. Here, we show a cell-based enzyme-linked immunosorbent
      assay (CbELISA) method for quantitative measurement of the binding activity of
      the 7G7/B6 antibody to the Kit-225-iG3 cell line expressing IL-2Ralpha antigen on
      the cell surface. The cell- and antigen-specificity of the assay was established
      using specific cell lines and irrelevant control antibodies. Satisfactory binding
      curves were demonstrated with Kit-225-iG3 cells grown between 3 and 25 passages
      in culture and at seed densities of 2 x 10(5)-4 x 10(6) cells/well. The assay
      shows reproducible dose-response curves in the concentration range of 10-1000
      ng/ml. The assay validation data presented here indicate that this CbELISA assay
      is quantitative, reproducible, robust, precise, and can be used to test the
      biological activity, lot to lot comparison, and stability of 7G7/B6 monoclonal
      antibody.

PMID- 12799043
TI  - Small molecule LFA-1 antagonists compete with an anti-LFA-1 monoclonal antibody
      for binding to the CD11a I domain: development of a flow-cytometry-based receptor
      occupancy assay.
AB  - The beta(2) integrin LFA-1 (CD11a/CD18) is a leukocyte-specific adhesion molecule
      that mediates leukocyte extravasation, antigen presentation, and T-cell-mediated
      cytolysis through its interaction with its counter-receptors, ICAM-1, ICAM-2, and
      ICAM-3. We have recently described a small molecule antagonist of LFA-1 (BIRT
      377) that inhibits LFA-1/ICAM-1 molecular interactions, LFA-1-dependent adhesion
      assays, antigen-induced proliferation of T-cells, and superantigen-induced
      production of IL-2 in vivo in mice. We have also recently described a unique
      monoclonal antibody, R3.1, which competes with BIRT 377 and its analogs for
      binding to both purified full-length LFA-1 and the purified recombinant I domain
      module. In this manuscript, we extend these studies to cell-based systems and
      utilize this unique reagent for the development of a receptor occupancy assay.
      Exploiting these observations, we have designed and validated an assay that
      allows us to measure receptor occupancy in vitro on monkey and human peripheral
      blood leukocytes and ex vivo in whole blood from monkeys dosed with small
      molecule LFA-1 antagonists. Further refinement of these reagents has led to the
      development of a Fab-based assay that allows rapid and reproducible analysis of
      whole blood samples. These optimized reagents allow for quantification of the
      number of receptors expressed on the cell surface and a more accurate
      quantitation of receptor occupancy.

PMID- 12799044
TI  - A fast Western blot procedure improved for quantitative analysis by direct
      fluorescence labeling of primary antibodies.
AB  - The procedures for Western blots have been around for a long time and recent
      developments have increased the sensitivity for luminescent techniques so that
      the need for radioactive probes has been limited to only a few applications.
      Nevertheless, most protocols require more than 6 h and are often performed over
      more than a day. The majority of techniques require a secondary antibody
      conjugated to an enzyme that catalyzes a color reaction in order to amplify a
      detectable signal. However, both processes, the binding of a secondary antibody
      and the catalyzed reaction with the dye, are sources for errors and the latter is
      disadvantageous for a signal that is linear over a larger range of detected
      antigen. In order to improve the procedure most commonly used for quantitative
      analysis and convenience, we investigated the use of fluorescence labeling of
      primary monoclonal antibodies against Escherichia coli RNA polymerase subunits
      (beta', sigmaE and sigmaFecI) and their use in Western blots. We achieved a
      sensitivity (<1 ng detectable protein) comparable to most luminescent techniques.
      Additionally, we reduced the procedure time significantly to less than 1 h after
      SDS-PAGE and transfer to a membrane. Above all, we obtained a linear signal over
      the range of 30 ng to 1 microg of protein (dependent on protein size) making
      quantitative analysis of Western blots easier and more reliable.

PMID- 12799045
TI  - Measuring the specific activity of the CD45 protein tyrosine phosphatase.
AB  - Many assays for protein tyrosine phosphatases (PTPs) rely on colorimetric
      substrates or more recently developed fluorescent substrates. Enzyme activity is
      measured but no assessment of specific activity is made, which is important since
      these enzymes can exist in an enzymatically inactive form. In this study, we have
      directly compared the relative sensitivity of assays using either colorimetric or
      fluorescent substrates and show the latter to be considerably more sensitive with
      as few as 0.2 x 10(6) cells required compared to 3 x 10(6) cells for the
      colorimetric method. We then describe a quick and sensitive protocol that
      measures both the phosphatase activity and amount of CD45, allowing the
      calculation of the specific activity. CD45 is captured from cell lysates using
      anti-CD45 monoclonal antibody coated onto a 96-well plate, and the phosphatase
      activity is measured using the substrate fluorescein diphosphate (FDP). The
      amount of CD45 protein bound in the wells is measured against a standard curve
      using an anti-CD45-HRP conjugate, and this value is used to derive the specific
      activity. We used this assay to demonstrate that exposure of Jurkat T cells, and
      primary CD4(+) T cells to H(2)O(2) decreases the specific activity of their CD45,
      mimicking the changes seen in some diseases. The assay is applicable to other
      cell types and phosphatases, and so its use may help to identify the presence of
      inactive but intact enzyme in cells, which may play an important regulatory role
      in vivo.

PMID- 12799046
TI  - Determination of efficiency of attachment of biotinylated antibodies to avidin
      linked, aqueous-based microcapsules by flow cytometry.
AB  - We used flow cytometry to determine the percentage of aqueous-based microcapsules
      bearing antibodies specific for various antigen-presenting cells (APCs) within a
      given population of putative APC-specific microcapsules. Flow cytometry offers a
      high-throughput, rapid and simple method to analyze antibody binding to
      noncellular, nonspherical material.

PMID- 12799047
TI  - A simple method for enriching populations of transfected CHO cells for cells of
      higher specific productivity.
AB  - To establish a simple and rapid method for the screening of stable recombinant
      Chinese hamster ovary (CHO) cell lines, we have developed a cell surface labeling
      technique using fluorescently tagged antibodies that bind to secreted target
      proteins at low temperature. Using fluorescence intensity as the sole criterion
      for selection of cells, we are able to enrich populations of highly productive
      cells using preparative flow cytometry sorting. Reiterative sorting based on
      selection of cells having the highest fluorescence intensity of cell surface
      labeled protein results in dramatic increases in specific cellular productivity.
      Using lymphotoxin-beta receptor IgG fusion protein as a model system, we have
      demonstrated a greater than 20-fold increase in specific productivity (0.49-11.5
      pg cell(-1) day(-1)) (pcd) without the use of methotrexate (MTX)-mediated
      selection or amplification. In addition, the flow cytometry used to enrich for
      and clone high producer cell lines has reduced development time by more than 50%
      and the number of screening assays by more than 10-fold. When a transfected
      population of CHO cells expressing a humanized version of the murine monoclonal
      antibody (mAb) AQC2 directed against human alpha 1 beta 1 integrin was subjected
      to the same treatment, a 25-fold improvement in specific productivity (0.3-8.0
      pcd) was observed. Furthermore, similar application of this technique to MTX
      amplified clones resulted in up to 120-fold overall improvement in specific
      productivity (up to 42 pcd). Greater than 20 examples are also presented to
      demonstrate the robustness and performance of this technique.

PMID- 12799048
TI  - Production and characterisation of a novel chicken IgY antibody raised against C
      terminal peptide from human thymidine kinase 1.
AB  - Egg yolk is a good source of highly specific antibodies against mammalian
      antigens because of the phylogenetic distance between birds and mammals. Chicken
      egg yolk immunoglobulins (IgY) were generated to a synthetic 31-amino acid
      peptide from the C-terminal of human HeLa thymidine kinase 1 (TK1) enzyme. The
      anti-TK1 IgY antibody was purified using affinity chromatography against the 31
      amino acid peptide. The purified antibody inhibited the catalytic activity of the
      TK1 enzyme in the CEM TK1(+) cells and recognized the 25-kDa subunit and
      tetrameric form of TK1, which has a pI value of 8.3. No immunoreaction was
      observed in CEM TK1(-) cells. Western blot of the serum TK1 (S-TK1) also showed
      that only a single band was found in the serum of patients with malignancies. No
      band was seen in healthy serum. Furthermore, dot blots and enhanced
      chemiluminescence (ECL) detection of S-TK1 performed on sera of preoperative
      patients with gastric cancer (GC) (n=31) and healthy controls (n=62) showed that
      the levels of S-TK1 in the sera of cancer patients were significantly different
      (P<0.01). Using ECL dot blots, 0.1 pg of TK1 in 3 microl sera could be detected.
      Immunohistostaining of tissues in the 11 advanced-stage cancer patients (four
      breast carcinomas, three hepatocarcinomas and four thyroid carcinomas) indicated
      that a strong staining of TK1 enzyme was found in the cytoplasm of malignant
      cells. No staining or weak staining was seen in normal tissues. We suggest that
      screening for TK1 using anti-TK1 IgY may be potentially useful for serological
      and immunohistochemical detection of TK1 as an early prognosis and for monitoring
      patients undergoing treatment.

PMID- 12799050
TI  - Rapid single-step FCGR3A genotyping based on SYBR Green I fluorescence in real
      time multiplex allele-specific PCR.
AB  - A polymorphism at position 559 in the cDNA of the FCGR3A gene encoding the
      FcgammaRIIIa generates two allotypes with either a valine (Val) or a
      phenylalanine (Phe) at amino acid position 158. This polymorphism is of major
      importance in immunopathology and in pharmacogenetics, especially monoclonal
      antibody treatments. In this study, we report a single-step and single-tube
      method for FCGR3A-158V/F genotyping by real-time multiplex allele-specific PCR
      and melting curve analysis in the presence of SYBR Green I fluorescent dye.
      Results obtained from 113 samples showed 100% accuracy compared to those obtained
      with a conventional PCR-based allele-specific restriction assay. Although this
      method requires expensive equipment, it is inexpensive in terms of consumables.
      It is also very rapid, reliable and suitable for large-scale analysis.

PMID- 12799049
TI  - Mammary gland-specific secretion of biologically active immunosuppressive agent
      cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in
      milk by transgenesis.
AB  - A major challenge in the field of transplantation is to prevent graft rejection
      and prolong graft survival. Tolerance induction is a promising way to achieve
      long-term graft survival without the need for potent immunosuppression and its
      associated side effects. The recent success of co-stimulatory blockade by the
      chimeric protein CTLA4Ig in the modulation of the recipient's immune system and
      the prolongation of graft survival in animal models suggests a possible
      application of CTLA4Ig in clinical transplantation. To produce sufficient amounts
      of CTLA4Ig for future clinical application, we sought to use the mammary gland as
      a bioreactor and produce CTLA4Ig in the milk of transgenic farm animals. Prior to
      the generation of transgenic farm animals, we tested our strategy in mice. Using
      the promoter of the sheep beta-lactoglobulin gene, we expressed our CTLA4Ig
      chimeric gene in the mammary gland of transgenic mice. The yield of CTLA4Ig was
      fivefold higher in transgenic milk than that from transfected cells. Purified
      milk-derived CTLA4Ig is biologically active and suppresses T cell activation. We
      showed that the production of CTLA4Ig in the milk has no adverse
      immunosuppression effect on the transgenic animals and the offsprings that were
      fed with the transgenic milk. The findings suggest that the approach to produce
      CTLA4Ig in milk by transgenesis is feasible; further studies involving farm
      animals are warranted.

PMID- 12799051
TI  - Morphometric analysis of cytolysis in cultured cell monolayers: a simple and
      versatile method for the evaluation of the lytic activity and the fate of LAK
      cells.
AB  - The assessment of cytolytic activity of killer cells may not only be useful to
      improve routine analysis, e.g., in clinical settings, but may also offer new
      opportunities for the fundamental analysis of the mutual interaction between
      cytotoxic cells and their targets. We have developed a morphometric method to
      estimate cytolytic activity of activated natural killer (NK) cells by measuring
      the clearance of a precultured confluent monolayer of adherent target cells,
      e.g., immortalized fibroblasts. Cytotoxic cells are inoculated on top of
      confluent monolayers of target cells and after 2 h, nonadherent cells are washed
      off and intact adherent cells are fixed and stained with a Coomassie blue
      solution. Elementary computer-assisted analysis of the resulting microscopic
      images and measurement of the cleared area provide us with a sensitive and
      reproducible parameter of target cell lysis. We found that the assay can be used
      with targets of very different origin, as long as they form confluent monolayers,
      and with different populations of killer cells. The morphometric cytotoxicity
      assay (MoCA) offers several advantages: storage of samples for postponed
      analysis, increased sensitivity as compared to radioactive assays, continuous
      visualization during assay, availability of targets and effectors for subsequent
      analysis after interaction.

PMID- 12799052
TI  - Multidisciplinary modelling of biomedical systems.
AB  - This paper describes general principles and example results of a new software
      tool being developed for physiologically-based modelling of biomedical systems
      within a multidisciplinary framework. The aim is to overcome some limitations of
      currently available software designed either for general purpose or for highly
      specialised modelling applications. In fact, general purpose tools usually impose
      explicit coding of mathematical model equations or non-intuitive system
      representations, whereas specialised software use domain-specific notations that
      allow efficient and convenient model building only for special classes of
      systems. The aim of the present study is to pursue intuitive representation of
      various, possibly interacting, types of biological systems described as
      interconnected physical components, such as mass and energy storage elements,
      active and passive transport or biochemical transformations. The presented
      software generates automatically the mathematical model equations that can be
      coded in different formats. This allows interoperability with other existing
      software, e.g. for numerical simulation, symbolic analysis or text processing. A
      multi-domain structural language has been defined for an intuitive, hierarchical
      and self-explanatory specification of physiological models. The proposed
      strategies may become useful for dissemination and integration of
      multidisciplinary modelling knowledge.

PMID- 12799053
TI  - Polygon reduction of 3D objects using Stokes' theorem.
AB  - Surface over volume rendering can be useful for many applications. However, the
      tremendously large number of polygons composing the surface primitives should be
      reduced to a manageable size so as to utilize the capability of low cost hardware
      and software rendering engines, a standard Internet protocol and VRML format. In
      this paper, we propose a novel algorithm that deletes several vertices
      simultaneously by forming a closed arbitrary shaped boundary. The Stokes'
      theorem, used in electro-magnetic field analysis, was newly adapted to extract
      the arbitrary shaped boundary. The simultaneous deletion procedure provides a
      computational gain and increases the reduction ratio without sacrificing the
      topological distortion of the original mesh. Numerically synthesized polygonal
      objects and real CT data were tested to evaluate the performance of the new
      algorithm and to demonstrate the possibility of a medical rendering application.
      The new algorithm outperforms the conventional decimation algorithm in both
      computational and reduction efficiency.

PMID- 12799054
TI  - The instantaneous frequency of cardiovascular time series: a comparison of
      methods.
AB  - The instantaneous frequency (IF) of cardiovascular time series is used to
      describe the time-varying spectral contents of the characteristic frequency bands
      that are of interest for psychophysiological and cardiovascular research. Four
      methods to compute IF of band-limited, monocomponent, and analytical
      cardiovascular time series were compared by means of simulated time series
      contaminated with additive noise. These four methods are: the method using the
      inverse Fourier transform of uncorrelated time-slices of the Wigner-Ville
      distribution, the discrete time-frequency transform, the circular mean direction
      of the time-slices of the Wigner-Ville distribution, and the central finite
      difference of the phase. The time resolution of the estimates is optimal and is
      inversely related to the bandwidth of the frequency components, as given by the
      uncertainty principle of Gabor. At periods in time where the signal fulfills the
      requirements of the model signal, the four estimates of IF are numerically equal;
      only the circular mean direction showed a slight deviation from the other
      estimates. Although the estimates of IF differ at sudden phase shifts at low
      amplitude, i.e. at points where the signal locally does not comply with the
      requirements of the model signal, overall the four methods produce comparable
      estimates of IF of a cardiovascular time series at an optimal time resolution.

PMID- 12799055
TI  - An application of a muscle model to study electromyographic signals.
AB  - A simulation program for research and teaching electromyography (EMG) has been
      developed. It has a great number of parameters that may be optionally changed in
      simulations of normal and diseased muscle. The simulator is user-friendly and
      fast and can actually be run without much help from the manual. It is easy to
      introduce new motor units (MU), to change MU and individual muscle fibre
      parameters, to insert an EMG electrode and to change its position. The model
      allows simulation of the most common pathological situations. The resulting
      signals are displayed in a conventional form. The generated EMG signals obtained
      with the three electrodes that have been used so far are reasonably similar to
      the signals obtained in real recordings. A few shortcomings in simulating, e.g.
      end plate zone and abnormal volume conduction characteristics do not seem to
      influence the principal results. The simulator can, therefore, be used in
      teaching and even for research.

PMID- 12799056
TI  - Internet (WWW) based system of ultrasonic image processing tools for remote image
      analysis.
AB  - Ultrasonic Doppler color imaging can provide anatomic information and
      simultaneously render flow information within blood vessels for diagnostic
      purpose. Many researchers are currently developing ultrasound image processing
      algorithms in order to provide physicians with accurate clinical parameters from
      the images. Because researchers use a variety of computer languages and work on
      different computer platforms to implement their algorithms, it is difficult for
      other researchers and physicians to access those programs. A system has been
      developed using World Wide Web (WWW) technologies and HTTP communication
      protocols to publish our ultrasonic Angle Independent Doppler Color Image (AIDCI)
      processing algorithm and several general measurement tools on the Internet, where
      authorized researchers and physicians can easily access the program using web
      browsers to carry out remote analysis of their local ultrasonic images or images
      provided from the database. In order to overcome potential incompatibility
      between programs and users' computer platforms, ActiveX technology was used in
      this project. The technique developed may also be used for other research fields.

PMID- 12799057
TI  - A high resolution workstation prototype for diagnosis of digital mammograms.
AB  - The development of a total digital high resolution mammography display system
      must meet a number of requirements that remain a challenge nowadays, most
      probably because of the special nature of breast imaging. In this paper, we
      discuss our particular approach to address some problems concerning the
      complexity of soft-copy diagnosis in digital mammography, such as image quality
      and user interface evaluation. Based on the experience obtained in the previous
      implementation of a medical image browser, a more ambitious project is being
      developed at the Department of Radiology of the University of Santiago de
      Compostela (Spain) in collaboration with the Department of Medical Informatics of
      INTELSIS, an emerging software company in our country. This new system will
      provide complete support to display, store and analyze mammographic studies in
      digital format.

PMID- 12799058
TI  - Narrative electronic patient records as source of discharge diagnoses.
AB  - OBJECTIVE: To evaluate the consistency of diagnostic data extracted from
      narrative electronic patient record (EPR) notes compared with the data from a
      patient administrative system (PAS). To assess potential benefit of using EPR
      notes as source of diagnosis data and as basis for case identification. DESIGN:
      Construction of a computer algorithm to extract ICD-9 codes from narrative EPR
      notes. Assessment of consistency and reliability of the diagnostic codes
      retrieved from EPR notes and PAS. Estimation of efficiency of case identification
      based on data from PAS and EPR. RESULTS: Diagnosis codes were retrieved from PAS
      with sensitivity of 0.989 and the positive predictive value (PPV) was 0.993.
      Codes were retrieved from EPR with sensitivity of 0.908 and PPV of 0.990.
      Combining these two sources increased sensitivity to 0.999. CONCLUSION: Discharge
      diagnoses were easily extracted from narrative EPR notes by automatic methods.
      Information extracted from record notes was not significantly different from the
      corresponding data in PAS, but EPR was incomplete as compared with PAS. Utilizing
      data extracted from EPR improved case identification significantly.

PMID- 12799059
TI  - A circulatory model for calculating non-steady-state glucose fluxes. Validation
      and comparison with compartmental models.
AB  - This study presents a circulatory model of glucose kinetics for application to
      non-steady-state conditions, examines its ability to predict glucose appearance
      rates from a simulated oral glucose load, and compares its performance with
      compartmental models. A glucose tracer bolus was injected intravenously in rats
      to determine parameters of the circulatory and two-compartment models. A
      simulated oral glucose tolerance test was performed in another group of rats by
      infusing intravenously labeled glucose at variable rates. A primed continuous
      intravenous infusion of a second tracer was given to determine glucose clearance.
      The circulatory model gave the best estimate of glucose appearance, closely
      followed by the two-compartment model and a modified Steele one-compartment model
      with a larger total glucose volume. The standard one-compartment model provided
      the worst estimate. The average relative errors on the rate of glucose appearance
      were: circulatory, 10%; two-compartment, 13%; modified one-compartment, 11%;
      standard one-compartment, 16%. Recovery of the infused glucose dose was 93+/-2,
      94+/-2, 92+/-2 and 85+/-2%, respectively. These results show that the circulatory
      model is an appropriate model for assessing glucose turnover during an oral
      glucose load.

PMID- 12799060
TI  - An advanced method in fetal phonocardiography.
AB  - The long-term variability of the fetal heart rate (FHR) provides valuable
      information on the fetal health status. The routine clinical FHR measurements are
      usually carried out by the means of ultrasound cardiography. Although the
      frequent FHR monitoring is recommendable, the high quality ultrasound devices are
      so expensive that they are not available for home care use. The passive and fully
      non-invasive acoustic recording called phonocardiography, provides an alternative
      low-cost measurement method. Unfortunately, the acoustic signal recorded on the
      maternal abdominal surface is heavily loaded by noise, thus the determination of
      the FHR raises serious signal processing issues. The development of an accurate
      and robust fetal phonocardiograph has been since long researched. This paper
      presents a novel two-channel phonocardiographic device and an advanced signal
      processing method for determination of the FHR. The developed system provided 83%
      accuracy compared to the simultaneously recorded reference ultrasound
      measurements.

PMID- 12799061
TI  - Improvement of exogenous DNA nuclear importation by nuclear localization signal
      bearing vectors: a promising way for non-viral gene therapy?
AB  - Several vectors have been developed in order to target genes to specific cells.
      Virus-based vectors lead to a high transfection efficiency in vitro, but display
      important disadvantages such as pathological risks, which they expose to
      patients. Plasmid-associated chemical vectors lack these disadvantages, but allow
      only a very low efficiency of transgene expression. Most of the non-viral-based
      gene transfer techniques developed until now mainly focused their efforts to
      overcome the problem of DNA entry into the cell. Some recent works, however, have
      begun to investigate the nucleus entry problem and suggest that the trafficking
      of DNA from cytosol to the nucleus may be improved by using the nuclear
      localization signal (NLS) found in some nuclear proteins. If the vector contains
      one or several NLS, either as covalently or non-covalently DNA-linked peptides, a
      competition may take place between the rate of dissociation of the DNA-vector
      complexes and the rate of loading of the complexes to the NLS-mediated nucleus
      importation machinery. This equilibrium may be displaced towards the importation
      pathway by the use of NLS-bearing proteins instead of peptides. The possibility
      of recruiting normal endogenous cellular pathways of nuclear uptake to promote
      entry of exogenously applied DNA through the nuclear pore complex would, thus,
      seem promising. Nevertheless, attempts to improve the transport of DNA to the
      nucleus through the use of NLSs have achieved limited success. Although these
      systems show improved transgene expression, little is known about how they
      function in transfected cells, and the optimal formulation for gene expression is
      yet to be determined.

PMID- 12799062
TI  - Evolutionary conservancy of the endocytic and trafficking machinery in the
      unicellular eukaryote Paramecium.
AB  - Molecular search for the homologues of the mammalian proteins in the unicellular
      eukaryote Paramecium involved in endocytosis and membrane trafficking is
      discussed. We cloned and sequenced the gene fragments encoding the following
      components participating in endosome formation, sorting and maturation of the
      proprotein precursors, respectively, dynamin 2, Rab7 and furin. There is a proof
      that all these genes are expressed in this unicellular organism. The function of
      the identified immunoanalogues of the above described components of Paramecium
      endocytic machinery as well as a high degree of sequence homology to the
      respective human counterparts points to the evolutionary conservancy of these
      pathways.

PMID- 12799063
TI  - Chondrogenic differentiation during midfacial development in the mouse: in vivo
      and in vitro studies.
AB  - Because the mouse is now the main model for developmental research of all types,
      it is important to understand the basic developmental pattern of various organs.
      The first aim of the present study was to establish normal prenatal developmental
      standards of the cartilaginous nasal capsule during embryonic development of the
      mouse. For this purpose we have performed sagittal and coronal sections ranging
      from E12.5 to E18.5 in gestation age. The primordia of the nasal septal cartilage
      is recognizable around the 14th embryonic day as demonstrated by the
      metachromatic toluidine blue staining and by immunostaining of type II collagen.
      Northern blot analysis of the transcription factors Cart-1 and Sox-9 indicated
      maximum mRNA levels at E12.5 then a decreased expression during the following
      days of gestation. Type II collagen and aggrecan mRNA levels are constant during
      the embryonic period. In the second part of this study, we have established a
      primary culture system where chondrocytes were isolated from E.18 mouse embryo
      nasal septum. The purpose of this second part was to assess if chondrocytes could
      further differentiate in vitro until the hypertrophic phase and matrix
      mineralization. After the condensation phase, the cells synthesize an
      extracellular matrix including type II collagen and aggrecan. Progressively,
      typical cartilaginous nodules composed of clusters of round cells are visible,
      then increase in size and finally mineralize at day 12 of culture. Cart-1 and Sox
      9 mRNA levels remain constant throughout the cultures, whereas type II collagen
      and aggrecan gradually decrease. Ultrastructural observations of the nodules show
      typical chondrocytes embedded in a dense network of fibers with matrix vesicles
      and mineralized foci. Other ultrathin sections revealed the presence of
      chondrons, typical of hyaline cartilage. Results from this study provide useful
      tools to further investigate morphogenesis and differentiation of the
      cartilaginous nasal capsule, and could in the future serve as a basic
      developmental standard.

PMID- 12799064
TI  - The interaction of two classes of nuclear vesicles is induced by the dissociation
      of soluble proteins from one class of vesicles.
AB  - The regulatory mechanism of fusion steps in nuclear envelope assembly was studied
      in vitro using cell-free extracts of Xenopus eggs. The nuclear envelope is formed
      only around the chromatin at the end of mitosis. Two kinds of vesicles are
      required for nuclear envelope assembly (J. Cell Biol. 112 (1991) 545). Light
      vesicles (LVs) have the chromatin-binding activity, but cannot fuse solely. On
      the other hand, heavy vesicles (HVs) neither bind to the chromatin nor LVs, but
      are needed for the fusion event. Therefore, the association of HVs with LVs that
      bind to the chromatin is required at a first step during the fusion of vesicles.
      We found that salt-treated HVs inhibited the binding of LVs to the chromatin. In
      addition, when salt-treated HVs were pretreated with the proteins in the residue
      of salt-treatment of HVs, LVs recovered the chromatin-binding activity. In
      contrast, salt-treatment of LVs did not influence the binding of LVs with
      chromatin. By using a fluorescence microscopy assay, we showed directly that salt
      treated HVs associated with LVs or salt-treated LVs, but HVs did not. These
      results suggest that soluble mask proteins on HVs keep the two distinct vesicles
      separate. We propose that the dissociation of mask protein on HVs allows HVs to
      bind with LVs that are located on the chromatin, subsequently the fusion of each
      vesicle occurs and the nuclear envelope is formed.

PMID- 12799065
TI  - The acid phosphatase positive organelles of the Giardia lamblia trophozoite
      contain a membrane bound cathepsin C activity.
AB  - We found a dipeptidyl aminopeptidase activity in the parasitic protozoan Giardia
      lamblia with properties similar to the lysosomal cathepsin C of rat-liver
      lysosomes. Subcellular fractionation of this parasite indicated that the
      cathepsin C activity is located in organelles not distinguishable from the ones
      containing acid phosphatase, a known marker enzyme of Giardia lysosome-like
      peripheral vesicles. Contrary to the rat lysosomal enzyme, Giardia cathepsin C
      behaved like a membrane protein. Moreover, the enzyme was not solubilized by
      Triton X-100 or Triton X-100/SDS at 0 degrees C but could be substantially
      solubilized by octylglucoside, Triton X-100 at 37 degrees C or by a pretreatment
      with the cholesterol complexing agent beta-cyclodextrin before the Triton/SDS
      treatment carried out at 0 degrees C. These observations suggest that
      binding/anchorage of this enzyme to membranes occurs in cholesterol-rich
      microdomains.

PMID- 12799066
TI  - A functional deadenylation assay identifies human CUG-BP as a deadenylation
      factor.
AB  - CUG-BP is a human nuclear and cytoplasmic RNA-binding protein. A role in the
      control of alternative splicing has been reported, but to date no cytoplasmic
      function for this protein has been demonstrated. A close sequence homolog of CUG
      BP is EDEN-BP that is required for the specific cytoplasmic poly(A) tail
      shortening of certain mRNAs after fertilization of Xenopus eggs. Here, we show
      that human CUG-BP and Xenopus EDEN-BP have very similar RNA-binding
      specificities. In addition, we use a deadenylation assay to show that CUG-BP is
      able to act as a deadenylation factor. In contrast, a mutant form of CUG-BP,
      though still able to bind to RNA with a specificity similar to that of wild-type
      CUG-BP, does not act as a deadenylation factor. It is suggested that the CUG
      expansion associated with Type 1 myotonic dystrophy can affect the function or
      the activity of CUG-BP, leading to a trans-dominant effect on normal RNA
      processing. The results presented here identify CUG-BP-dependent deadenylation as
      a potential cytoplasmic target for this trans-dominant effect.

PMID- 12799067
TI  - Basolateral Ca2+-dependent K+-channels play a key role in Cl- secretion induced
      by taurodeoxycholate from colon mucosa.
AB  - The diarrhea associated with malabsorption of bile salts such as the secondary
      hydrophobic taurodeoxycholate (TDC) may be partly explained by the TDC-induced
      increase in colon Cl(-) secretion. We, therefore, investigated the effects of TDC
      (0.5-8 mM) on electrical parameters and electrolyte transport of rat proximal
      colon mucosa mounted in Ussing chambers. Colonic secretion, measured as short
      circuit current (I(SC)), progressively increased on mucosal incubation with TDC
      ranging 0.5-2 mM; up to TDC 2 mM, a spontaneous recovery toward control values
      with no changes in epithelial resistance (Rt), and lactate dehydrogenase (LDH)
      release was observed. In contrast, for TDC > 2 mM, I(SC) increased further and
      the effect was progressive and associated with a significant decrease in the Rt
      and increased LDH release, implying a cytolytic effect. Mucosal preincubation
      with the Cl(-) channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid
      (NPPB), fully prevented the precytolytic effect of TDC on I(SC). Serosal
      preincubation with furosemide, a Na(+)/K(+)/2Cl(-) cotransporter inhibitor,
      significantly reduced TDC-induced increase in I(SC). Inhibition of the
      basolateral Ca(2+)-dependent K(+) channel-rSK4-with serosal clotrimazole or
      incubation with mucosal Ca(2+)-free (EGTA) buffer completely prevented
      precytolytic TDC-induced increase in I(SC). In conclusion, Cl(-) secretion is
      activated in colon mucosa by TDC low concentrations; while at higher
      concentrations, a detergent cytotoxic effect intervenes. Activation of the Ca(2+)
      dependent basolateral K(+) pathway, through TDC-induced apical Ca(2+) influx,
      provides the Na(+)/K(+)/2Cl(-) basolateral activation, thereby the driving force
      for the apical exit of Cl(-) ions. These findings further enhance the knowledge
      of the pathogenic mechanisms of diarrhea associated with bile salt malabsorption.

PMID- 12799069
TI  - BEN/DM-GRASP/SC1 expression during mouse facial development: differential
      expression and regulation in molars and incisors.
AB  - The cell adhesion molecule BEN/DM-GRASP/SC1 is expressed in a variety of tissues
      during embryogenesis. Here, we studied the expression pattern of BEN/DM-GRASP/SC1
      in different organs involved in facial mouse development, especially in the
      developing teeth. BEN/DM-GRASP/SC1 was expressed in nose, whisker, gland, and
      tongue epithelia, as well as in myogenic mesenchyme. In molars, BEN/DM-GRASP/SC1
      was firstly expressed in the condensed mesenchyme and thereafter expression was
      confined to mesenchymal cells of the dental follicle. In contrast, in incisors,
      transient BEN/DM-GRASP/SC1 expression was restricted to epithelium. In tissue
      recombination experiments, BEN/DM-GRASP/SC1 expression in mesenchyme was
      activated by molar, but not incisor epithelium.

PMID- 12799070
TI  - From mesoderm to blood islands: patterns of key molecules during yolk sac
      erythropoiesis.
AB  - Several identified genes play key roles in the specification of the blood-forming
      system, from commitment of mesoderm to differentiation of hemopoietic and
      endothelial cells. We have thoroughly analyzed the expression dynamics of some of
      these genes during yolk sac erythropoiesis in the chick embryo. The study
      includes transcription factors which are known to participate in multimeric
      complexes: GATA-1, -2, SCL/tal-1 and Lmo2 (whose avian orthologue we have
      cloned), VEGF-R2, a critical regulator of hemopoietic and endothelial commitment,
      and hemoglobin used as a marker of the last step in erythroid differentiation.
      Several findings were unexpected. (1) Two distinct patterns were revealed for
      GATA-2, first: low expression, ubiquitous in all mesodermal cells, as soon as
      cells ingress through the primitive streak; secondly: high, blood island-specific
      expression. (2) VEGF-R2 is coexpressed with GATA-2 at the level of the primitive
      streak. (3) SCL and Lmo2 expression is restricted to presumptive hemangioblasts.
      (4) The up-regulation of GATA-2 in newly formed blood islands is shortly followed
      by GATA-1 expression. (5) Lmo2 is up-regulated in blood island angioblasts thus
      appearing as one of the earliest markers for endothelial cell commitment. VEGF-R2
      is down-regulated in hemopoietic cells prior to GATA-2, SCL/tal-1, Lmo2 and GATA
      1 in erythroblasts.

PMID- 12799071
TI  - Expression of Raldh2, Cyp26 and Hox-1 in normal and retinoic acid-treated Ciona
      intestinalis embryos.
AB  - Spatially regulated synthesis and degradation of retinoic acid (RA) organize
      embryonic pattern formation in vertebrate embryos. Here, we show expression
      pattern of genes encoding Ciona intestinalis homologs of the retinaldehyde
      dehydrogenase, RALDH2, and the cytochrome P450 RA-degrading enzyme, CYP26, in
      normal and RA-treated embryos. The Ciona homolog of Raldh2, Ci-Raldh2, was
      expressed in a few muscle-lineage blastomeres in the middle gastrula. Strong
      expression was then restricted to the anterior-most three muscle cells on each
      side of the tailbud embryo. The Ciona homolog of Cyp26, Ci-Cyp26, was expressed
      in the presumptive brain cells in the middle gastrula. The expression was then
      upregulated in the neck region. The posterior end of the tail was also weakly
      stained. Non-overlapping expression domains of Ci-Raldh2 and Ci-Cyp26 look
      similar to those in vertebrates, although the expression of both genes was
      restricted to a small number of cells in Ciona embryos. RA upregulated Ci-Cyp26
      expression and slightly downregulated Ci-Raldh2 expression in the tailbud embryo.
      We also show expression pattern of a Hox-1 ortholog (CiHox-1) in the Ciona
      embryo. CiHox-1 was expressed in two separated regions of the nerve cord and neck
      epidermis at the neurula stage. Expression pattern of these three genes are
      essentially similar to that in vertebrates.

PMID- 12799072
TI  - Expression of Netrin-1 and its two receptors DCC and UNC5H2 in the developing
      mouse lung.
AB  - The ligand Netrin-1 and its receptors DCC and UNC5H2 are critical for the
      regulation of neuronal migration in nervous system development. Here we
      demonstrate expression of these molecules in lung development. The mRNA
      expression profiles of Netrin-1, DCC and UNC5H2 are developmentally regulated
      during embryonic mouse lung formation. Netrin-1 shows a bimodal expression
      pattern with elevated mRNA levels early followed by a second peak in late
      gestation. Peak expression of DCC occurs early in development whereas expression
      of UNC5H2 peaks late in development. We also demonstrate localization of Netrin
      1, DCC and UNC5H2 during the stages of lung development. We present evidence that
      these proteins are modulated spatially in the mesenchyme and epithelium during
      lung organogenesis.

PMID- 12799073
TI  - cDNA cloning and spatiotemporal expression during avian embryogenesis of hnRNP
      A1, a regulatory factor in alternative splicing.
AB  - Alternative splicing and selective transport of RNA transcripts from cell nuclei
      are important regulatory mechanisms of gene expression during embryonic
      development. Here we report the molecular characterization and developmental
      expression in several tissue and organ systems of chicken hnRNP A1, a nucleo
      cytoplasmic 'shuttle' protein which in mammalian systems has been shown to
      function in the regulation of RNA alternative splicing by antagonizing
      constitutive splicing factors such as SF2/ASF. We show that hnRNP A1 is
      represented in the chicken by a single gene which is widely expressed at early
      embryonic stages, with particularly high levels of expression in the brain, skin,
      developing gut, and other ectodermal and endodermal derivatives. At later stages,
      expression of its mRNA and protein product become progressively confined to
      specific organ primordia and cell types, where both transient and persistent
      expression patterns are observed. HnRNP A1 protein is expressed at sites of
      active neurogenesis in the developing central and peripheral nervous systems,
      regions of known extensive alternative splicing.

PMID- 12799074
TI  - cBlimp-1 expression in chick limb bud development.
AB  - Blimp is a transcriptional repressor that has been identified in humans, mice and
      frogs. Here, we describe the cloning of the gene that encodes for the chick
      homolog of Blimp, cBlimp-1, and the tempo-spatial expression pattern of cBlimp-1,
      during chick development. cBlimp-1 whose gene product shares a high level of
      identity with its homologs from other organisms, was found to be expressed in the
      apical ectodermal ridge and posterior dorsal ectoderm of developing limb buds. In
      addition, cBlimp-1 is expressed in the developing eyes, branchial arches and otic
      placodes.

PMID- 12799075
TI  - Expression of the E3 SUMO-1 ligases PIASx and PIAS1 during spermatogenesis in the
      rat.
AB  - PIASx and PIAS1, two members of the conserved protein inhibitor of activated STAT
      (PIAS) family, are able to interact with and modulate activities of several
      distinct nuclear proteins, including androgen receptor (AR). PIASx and PIAS1 also
      function as E3-type ligases in small ubiquitin-related modifier 1 modifications.
      To gain better insight into the physiological roles of PIASx and PIAS1 in vivo,
      their cell-type specific expression and regulation were analyzed during
      testicular development and spermatogenesis in the rat. The expression of both
      PIASx and PIAS1 was low or undetectable in newborn rats. PIASx mRNA started to
      accumulate after day 20 of postnatal life, whereas expression of PIAS1 mRNA
      increased around day 30 after birth. In the adult rat testis, both PIASx and
      PIAS1 mRNA were present in Sertoli cells and in germ cells in the seminiferous
      epithelium at all stages. However, PIASx mRNA was more abundant in spermatocytes
      than in other cell types, whereas higher levels of PIAS1 mRNA were detected in
      late spermatocytes and round spermatids than in early spermatocytes. Since PIASx
      and PIAS1 accumulate in developing male germ cells, their regulatory functions
      are not only restricted to AR in Sertoli cells, but they also participate in
      molecular processes during meiosis.

PMID- 12799076
TI  - Expression of Wnt genes during mouse preimplantation development.
AB  - Pattern formation in the mouse preimplantation embryo is tightly regulated and
      essential for successful development. Wnt genes are known to regulate cell
      interactions and cell fate in invertebrates and vertebrates and, therefore, may
      play a role in the specification of cell lineages and cellular interactions that
      occur in preimplantation development. Using degenerate primers based on conserved
      protein sequences in Wnt coding regions, we have found evidence for Wnt gene
      expression at the blastocyst stage of mouse preimplantation development. We have
      identified sequences encoding Wnts3a and 4 and confirmed that these are present
      as transcripts in early development by using reverse transcriptase-polymerase
      chain reaction (RT-PCR) with specific primers located in the 5' half of these Wnt
      genes. Studies on the timing of expression showed that Wnt3a transcripts were
      present in 2-cell embryos which may represent maternally or embryonically derived
      transcripts since the major transition of maternal to zygotic gene expression
      occurs during the late 2-cell stage. Both Wnt3a and 4 transcripts were detected
      in some precompact 4/8-cell stages with consistent expression detected in all
      compact 8-, 16-cell and blastocyst stages. To our knowledge, expression of Wnt
      genes has not been previously described at such an early stage of mammalian
      development.

PMID- 12799077
TI  - Cloning and embryonic expression analysis of the mouse Gbx1 gene.
AB  - We report the cloning of a cDNA encoding the complete mouse Gbx1 coding region as
      well as a comparative expression analysis of Gbx1 and Gbx2 during murine
      development. Gbx1 is expressed first during gastrulation and later in a dynamic
      pattern in the central nervous system, including rhombomeres 3 and 5, optic
      vesicles, and the medial ganglionic eminence. Gbx1 expression is not upregulated
      in Gbx2 null homozygotes. Therefore, the only regions of potential genetic
      redundancy are where Gbx1 and 2 are normally coexpressed: the primitive streak,
      regions of the ventricular zone of the neural tube and the medial ganglionic
      eminence. Finally, we demonstrate that neither Gbx1 nor Gbx2 require FGF8 for
      expression during gastrulation, contrary to previous published reports.

PMID- 12799078
TI  - Differential regulation of Period 2 and Period 3 expression during development of
      the zebrafish circadian clock.
AB  - Circadian ( approximately 24h) clocks are endogenous time-keeping systems that
      drive the daily biological rhythms observed in most living organisms. The
      oscillation is generated by a transcriptional/translational autoregulatory
      feedback loop that is reset by external time cues such as the light/dark cycle
      and which in turn controls rhythms in physiology and behavior through downstream
      clock-controlled genes (Nature 417 (2002) 329). Genetic and biochemical analysis
      of Drosophila and mammalian clock genes has provided a comprehensive model for
      the molecular oscillator that generates these rhythms, but the ontogeny of this
      oscillator remains poorly understood. A circadian oscillator involving the clock
      genes Per3 and Rev-erb alpha was identified during early development in zebrafish
      (Science 289 (2000) 297). Here, we report the isolation of zebrafish Per2 and
      show the presence of a Per2 maternal mRNA in early embryos as for Per3. However,
      Per2 rhythmic expression occurs late during embryogenesis as compared to that of
      Per3. Furthermore, our data indicate that Per2 is not required during
      embryogenesis for the rhythmicity of physiological outputs such as melatonin
      synthesis. In addition, Per2 but not Per3 is constitutively expressed in the
      developing olfactory bulb and pituitary. This differential spatio-temporal
      expression patterns suggest specific roles for Per2 and Per3 in the establishment
      of the embryonic circadian system.

PMID- 12799079
TI  - Chick receptor tyrosine phosphatase Psi is dynamically expressed during
      somitogenesis.
AB  - To study the role of receptor tyrosine phosphatases in vertebrate development, in
      particular somitogenesis, we have cloned chick receptor tyrosine phosphatase Psi
      (cRPTPPsi). cRPTPPsi is expressed in a dynamic fashion in the somites to-be
      formed and uniformly throughout the presomitic mesoderm. In differentiating
      somites, cRPTPPsi expression gets restricted to the dermomyotome. In addition
      cRPTPPsi is expressed in the developing intermediate mesoderm, in neurogenic and
      sensory organs, the limb bud and the developing heart.

PMID- 12799080
TI  - Structure of the zebrafish fasciclin I-related extracellular matrix protein
      (betaig-h3) and its characteristic expression during embryogenesis.
AB  - betaig-h3, which is structurally related to the insect fasciclin I, is assumed to
      act as a cell adhesion molecule through binding to cell-surface integrins. In
      this study, we obtained cDNA clones for the zebrafish orthologue of betaig-h3 and
      examined the expression of the gene (betaig-h3) in zebrafish embryos using in
      situ hybridization. Expression is first seen at the bud stage in the presomitic
      mesoderm. Throughout the somitogenesis stage, betaig-h3 is expressed in all the
      segmented somites, as well as in the presomitic mesoderm (S0 and S-I). High
      expression is observed in the dorsolateral part of the somite until the mid
      somitogenesis stage. At late somitogenesis stages, the betaig-h3 expression in
      the dorsolateral somite fades away, while expression is upregulated in the
      ventromedial part of the somite that corresponds to the sclerotome. In embryos
      after completion of somitogenesis and fry after hatching, betaig-h3 continues to
      be expressed in the sclerotome. In addition, new expression starts in the
      mesenchyme cells in the head, pharyngeal arches, and pectoral fins. In the
      embryonic brain, expression is observed along the anterior and postoptic
      commissures, as well as along the optic nerve.

PMID- 12799081
TI  - Cadherin expression in the inner ear of developing zebrafish.
AB  - Cadherins are cell adhesion molecules that have been implicated in development of
      a variety of organs including the ear. In this study we analyzed expression
      patterns of three zebrafish cadherins (Cadherin-2, -4, and -11) in the embryonic
      and larval zebrafish inner ear using both in situ hybridization and
      immunocytochemical methods. All three Cadherins exhibit distinct spatiotemporal
      patterns of expression during otic vesicle morphogenesis. Cadherin-2 and Cadherin
      4 proteins and their respective mRNAs were detected mainly in the sensory patches
      and the statoacoustic ganglion (SAg), respectively. In contrast, cadherin-11mRNA
      was widely expressed earlier in the otic placode, and later became restricted to
      a subset of cells in the inner ear, including hair cells.

PMID- 12799083
TI  - The chloride conductance channel ClC-K is a specific marker for the Xenopus
      pronephric distal tubule and duct.
AB  - Almost nothing is known about the physiology of the pronephros other than that it
      is efficient at excreting large volumes of dilute urine. The distal segment of
      pronephric nephrons is the most poorly characterized region of this organ, in
      part due to the absence of early markers of this structure. In this report the
      embryonic expression of a Cl(-) conductance channel, x ClC-K, is described with
      high level transcription of this gene in the distal segment beginning at Xenopus
      stage 31. x ClC-K is also expressed at lower levels in the pronephric duct. This
      gene serves as a convenient marker for investigating the development of this
      physiologically critical nephric segment and also serves to identify the
      potential site of action of a component of the chloride handling system of the
      pronephros. As ClC-K channels are involved in human kidney disease the frog
      pronephros may be a useful system in which to study the in vivo activity of this
      channel.

PMID- 12799082
TI  - Molecular analysis and developmental expression of the Sex-lethal gene of Sciara
      ocellaris (Diptera order, Nematocera suborder).
AB  - This paper reports the cloning and characterization in Sciara ocellaris of the
      gene homologous to Sex-lethal (Sxl) of Drosophila melanogaster. This gene plays
      the key role controlling sex determination and dosage compensation in the latter
      species. The Sciara Sxl gene produces a single transcript encoding a single
      protein in both males and females. This protein, found inside the nucleus, is
      expressed in all tissues. Both Sciara and Drosophila Sxl proteins are highly
      conserved at their two RNA-binding domains. In both Sciara sexes, the Sxl protein
      co-localizes with transcription-active regions dependent on RNA polymerase II but
      not on RNA polymerase I. It would appear that in Sciara, Sxl does not appear to
      play the key discriminative role in controlling sex determination and dosage
      compensation that it plays in Drosophila.

PMID- 12799084
TI  - Sequence and embryonic expression of collagen XVIII NC1 domain (endostatin) in
      the zebrafish.
AB  - Endostatin, located in the NC1 domain of the collagen XVIII, is believed to
      inhibit the migration and proliferation of endothelial cells (Fed. Am. Soc. Exp.
      Biol. J. 15 (2001) 1044) and to play a role in axon guidance in Caenorhabditis
      elegans (J. Cell Biol. 152 (2001) 1219). Zebrafish is an attractive vertebrate
      model to determine the role of endostatin and the entire molecule of collagen
      XVIII during vertebrate development. Therefore, we have investigated the
      expression pattern of COL18A1 in zebrafish embryos from the segmentation to the
      hatching period stages.

PMID- 12799085
TI  - Distribution of phosphorylated Smad2 identifies target tissues of TGF beta
      ligands in mouse development.
AB  - Transforming growth factor beta (TGF beta) and related family members control the
      development of tissues by regulating cell proliferation, differentiation,
      migration and apoptosis. They transmit signals to the nucleus via phosphorylation
      of Smad proteins. Here, we used an antibody specifically recognising
      phosphorylated Smad2 (PSmad2) to identify tissues that have received signals of
      TGF beta family members acting via Smad2, e.g. TGF betas, activins and nodal. At
      embryonic day (E)5.5-E8.5, punctuated nuclear PSmad2 staining was scattered
      throughout the embryo. At E10.5-E12.5, specific zones of the neural tube and
      brain, ganglia, premuscle masses and precartilage primordia exhibited pronounced
      nuclear staining, while tissues undergoing epithelial-mesenchymal interactions
      showed prominent cytoplasmic staining. Interestingly, in the endocardium and most
      endothelial cells PSmad2 is not detected at E10.5-E12.5, although at E8.5 these
      cells were stained. These data document the cells that may have received a TGF
      beta-like stimulus and illustrate, for the first time, the dynamic regulation in
      space and time of phosphorylated Smad2 during mouse development.

PMID- 12799086
TI  - Immunolocalization of Zic2 expression in the developing mouse forebrain.
AB  - The Zic genes are a family of zinc finger transcription factors defined by their
      homology with the Drosophila gene, odd-paired (opa). Zic2 has a critical role in
      forebrain development, as is evidenced by the fact that, in both mice and humans,
      diminished expression results in the severe forebrain malformation known as
      holoprosencephaly. Published information indicates that Zic2 expression is most
      prominent in the dorsal neural tube/spinal cord and in the hindbrain; however,
      there is no published description of the pattern of expression of Zic2 in the
      developing forebrain where the main Zic2 associated phenotype occurs. Using a
      Zic2-specific antiserum, we present new information about the expression of Zic2
      in the developing mouse forebrain. In addition, we show that in sonic hedgehog
      (Shh) null mice, the expression of Zic2 is expanded ventrally in some structures
      while absent in others, suggesting that Shh has a role in regulating the
      expression of Zic2.

PMID- 12799087
TI  - Characterization of Netrin-1, Neogenin and cUNC-5H3 expression during chick
      dorsal root ganglia development.
AB  - The molecular mechanisms that control the axon pathfinding of different subtypes
      of dorsal root ganglia (DRG) neurons are poorly understood. To address whether
      Netrin-1-Neogenin/UNC-5 signaling contributes to sensory axon pathfinding, we
      cloned chick UNC5 homolog 3 (cUNC-5H3) and characterized the spatial, cellular
      and temporal expression patterns of Netrin-1, Neogenin and cUNC-5H3 in cutaneous
      and proprioceptive DRG neurons. We have found that Netrin-1 is only expressed by
      late-arising cutaneous neurons. In contrast, cUNC-5H3 expression is restricted to
      proprioceptive neurons. Neogenin is expressed in all DRG neurons. Our results
      indicate that the pathfinding molecules, Netrin-1 and cUNC-5H3 are differentially
      expressed by early cutaneous and proprioceptive neurons.

PMID- 12799088
TI  - Dynamic and coordinated expression profile of dbl-family guanine nucleotide
      exchange factors in the developing mouse brain.
AB  - Dbl-family guanine nucleotide exchange factors (Dbl-GEFs) act as activators of
      Rho-like small G proteins such as Rac1, Cdc42 and RhoA. Recently, some GEFs have
      been suggested to play important roles in the development of the nervous system.
      Here, we report a comprehensive expression profile analysis of 20 Dbl-GEFs that
      have yet to be well investigated. Northern analyses of murine mRNAs from brains
      of E13, E17, P7 and adult mice revealed expression of 18 out of 20 GEFs in some
      or all stages. In addition, we found that three human GEFs were highly expressed
      in the brain. Examination of the spatial expression patterns of five GEFs in
      embryos or neonatal brain by in situ hybridization revealed distinct patterns for
      each GEF. Our study reveals the dynamic and coordinated expression profiles of
      the Dbl-GEFs and provides a basic framework for understanding the function of
      GEFs in neural development.

PMID- 12799089
TI  - High sensitivity C-reactive protein as an independent risk factor for essential
      hypertension.
AB  - BACKGROUND: C-reactive protein (CRP), one of the hepatic acute phase reactants,
      has been associated with decreased endothelium-dependent relaxation, a potential
      risk factor for hypertension. However, the relationship between CRP and
      hypertension has not been well elucidated. The aim of this study is to assess
      whether circulating levels of CRP are independently related to essential
      hypertension. METHODS: We evaluated the relationship between high sensitivity CRP
      with blood pressure (BP) and several cardiovascular risk factors in a cross
      sectional survey of 8347 apparently healthy Korean persons. The CRP was measured
      by nephelometry. RESULTS: The subjects consisted of 4813 men and 3534 women, aged
      >/=20 years. Mean (SD) age and CRP level of the population were 47.1 (11.5) years
      and 1.12 (1.72) mg/L. Overall hypertension prevalence was 34%. There was a
      significant positive association between BP and the CRP level (P <.0001). After
      adjustment for age, sex, fasting blood sugar, triglyceride, low-density
      lipoprotein, body mass index, waist-hip ratio, high-density lipoprotein, the
      prevalence of hypertension by CRP was 1.267 (95% confidence interval [CI] 1.079
      1.487, P =.004), 1.253 (95% CI 1.062-1.477, P =.007), and 1.451 (95% CI 1.231
      1.711, P <.001) times higher in subjects in the second, third, and fourth
      quartiles of CRP, as compared to subjects in the first quartile. CONCLUSIONS: Our
      results suggest that the CRP level may be an independent risk factor for the
      development of hypertension in Korean persons. However, because of the cross
      sectional nature of our study, this finding should be confirmed in prospective
      cohort studies, aimed at elucidating the role of CRP in the prediction,
      diagnosis, and management of hypertension.

PMID- 12799090
TI  - Associations between nondipping of nocturnal blood pressure decrease and
      cardiovascular target organ damage in strictly selected community-dwelling
      normotensives.
AB  - BACKGROUND: In hypertensives, nondippers are more likely than dippers to suffer
      silent, as well as overt, hypertensive target organ damage. In this study, we
      investigated whether a nondipper status was associated with target organ damage
      in normotensives. METHODS: We performed ambulatory blood pressure (BP)
      monitoring, echocardiography, and carotid ultrasonography and measured
      natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with
      the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory
      BP <125/80 mm Hg. RESULTS: The left ventricular mass index (LVMI) and the
      relative wall thickness (RWT) measured by echocardiography were greater in
      nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38
      +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and
      brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14
      +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05).
      There were no significant differences in UAE and intima-media thickness measured
      by carotid ultrasonography. CONCLUSIONS: Normotensive nondipping may not reflect
      renal damage, but may have a predominant effect on cardiac damage. Nondipping of
      nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and
      may result in a cardiovascular risk independent of ambulatory BP levels in
      normotensives.

PMID- 12799091
TI  - Effect of amlodipine, quinapril, and losartan on pulse wave velocity and plasma
      collagen markers in patients with mild-to-moderate arterial hypertension.
AB  - BACKGROUND: Carotid-femoral pulse wave velocity (PWV) is a prognostic factor in
      arterial hypertension. Modification of PWV, apart from blood pressure (BP)
      lowering seems to be important in the evaluation of antihypertensive drugs. One
      of the underlying causes arterial stiffening is arterial wall fibrosis. Plasma
      collagen I metabolites: carboxy (PICP) and amino (PINP) propeptides are
      considered as a valuable approach in the assessment of arterial fibrosis. The
      purpose of the present study was to compare changes in BP, PWV, plasma
      aldosterone, and collagen metabolites after treatment with amlodipine, quinapril,
      and losartan. METHODS: One hundred eighteen patients with mild-to-moderate
      essential arterial hypertension were randomized to treatment with 10 mg/d of
      amlodipine (group 1), 20 mg/d of quinapril (group 2), or 2 x 50 mg/d of losartan
      (group 3). At baseline, and after 3 and 6 months analysis of variance was
      performed to compare changes in BP, PWV, aldosterone, PICP, and PINP among
      subjects with adequate BP control on monotherapy (group 1, n = 38, group 2, n =
      37, group 3, n = 24). RESULTS: Blood pressure decreased equally in all groups.
      Among patients with comparable BP values on monotherapy, only quinapril-treated
      patients showed a significant decrease in PWV, aldosterone, and PICP as compared
      with baseline values. Multiple regression analysis showed that PWV was
      significantly affected by: age (beta = 0.36; P =.021), systolic BP (beta = 0.45;
      P =.014), and PICP (beta = 0.27; P =.038). CONCLUSIONS: In hypertensive subjects
      PWV depends on age, systolic BP, and collagen synthesis. Of the three drugs with
      comparable BP-lowering efficacy only quinapril significantly decreases PWV,
      plasma aldosterone, and PICP.

PMID- 12799092
TI  - Differential effect of acute angiotensin II type 1 receptor blockade on the
      vascular and adrenal response to exogenous angiotensin II in humans.
AB  - BACKGROUND: Aldosterone stimulation by angiotensin II may not exclusively be
      mediated by the angiotensin II type 1 (AT(1)) receptor. We have, therefore,
      investigated the vascular and adrenal response to angiotensin II infusion without
      and with pretreatment with the AT(1) receptor antagonist valsartan (160 mg).
      METHODS: In nine healthy human volunteers, angiotensin II was administered
      intravenously at doses of 1, 3, and 10 ng/kg/min, each over 45 min. Arterial
      blood pressure (BP) was measured oscillometrically at 5-min intervals. Blood for
      the determination of plasma renin activity and aldosterone was taken before the
      start of the infusion, at the end of each infusion period, and 1 h after the
      infusion was stopped. RESULTS: Angiotensin II increased systolic and diastolic BP
      from 121 +/- 3/70 +/- 2 mm Hg to a maximum of 146 +/- 2/97 +/- 1 mm Hg (P <.001)
      and plasma aldosterone from 39.2 +/- 9.8 to 290.7 +/- 48.3 (P <.001). The
      increase in BP after exogenous angiotensin II was completely abolished in
      volunteers pretreated with valsartan, averaging 118 +/- 3/72 +/- 1 mm Hg by the
      end of the maximum angiotensin infusion dose. In contrast, plasma aldosterone
      stimulation by angiotensin II was only partially blunted by concomitant AT(1)
      receptor blockade (98.9 +/- 16.3 pg/mL after the maximal dose of angiotensin II).
      CONCLUSIONS: These results indicate that although the vascular response to
      exogenous angiotensin II is exclusively mediated by the AT(1) receptor, the
      effects of angiotensin II on adrenal aldosterone release may involve other
      pathways.

PMID- 12799093
TI  - Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone
      mass of hypertensive subjects: relationship with angiotensin converting enzyme
      polymorphisms.
AB  - BACKGROUND: Many alterations in extracellular metabolism of calcium have been
      associated to hypertension, but the number of studies relating this disease with
      osteoporosis is extremely low. This study clarifies the therapeutic effect of
      three treatments-quinapril, quinapril + hydrochlorothiazide (HCTZ), enalapril-on
      bone remodeling markers, bone mineral density (BMD) in hypertensive patients, and
      relationship with angiotensin converting enzyme (ACE) polymorphism. METHODS: This
      open, prospective study included 134 patients with low-to-moderate hypertension
      and stable BMD according to Joint National Committee criteria and 96 patients
      completed the study. After a washout period, patients were randomized to one of
      the three treatments, which they received for 1 year. Analyses of blood and urine
      samples and densitometric studies on lumbar spine were performed. RESULTS:
      Calcium and 25-hydroxyvitamin D levels increased (9.5 +/-0.3 and 9.6 +/-0.3
      mg/dL, P =.01 and 46 +/-22 and 58 +/-22 nmol/L, P =.026, respectively) in the
      quinapril-treated group and calcium levels increased (9.4 +/-0.6 and 9.8 +/-0.4
      mg/dL, P =.001) in the quinapril-HCTZ-treated group. The 1, 25-dihydroxyvitamin D
      levels, calciuria, and calcium/creatinine ratio decreased (64 +/-23 and 43 +/-16
      nmol/L, P =.0001;209 +/-93 and 161 +/-93 mg/24 h, P =.0022;0.21 +/-0.09 and 0.17
      +/-0.11, P =.04, respectively). In the enalapril-treated group 1, 25
      dihydroxyvitamin D levels (61 +/-27 and 42 +/-19 nmol/L, P =.0022) decreased.
      Only women presented a statistical significance (1.064 +/-0.16 g/cm(2), P =.034)
      between ID+II polymorphism and BMD decrease, and between DD polymorphism with
      less BMD under baseline conditions and a BMD increase (1.070 +/-0.16 g/cm(2), P
      =.017) after ACE inhibitor treatment. CONCLUSIONS: The ACE inhibitors have a
      beneficial effect on BMD and calcium metabolism alterations in hypertensive
      subjects. Concerning BMD response, women presenting with the II+ID polymorphism
      had a poor response to antihypertensive drug treatment, whereas women with the DD
      polymorphism responded better. This is the first study demonstrating a
      relationship between ACE polymorphism and BMD response and antihypertensive ACE
      inhibitor treatment.

PMID- 12799094
TI  - Defining the antihypertensive properties of the angiotensin receptor blocker
      telmisartan by a practice-based clinical trial.
AB  - Traditional randomized controlled clinical trials are designed to define the
      specific properties of individual antihypertensive drugs but do not provide full
      information about their use in clinical practice. To carry out a large-scale
      practice-based open-label trial to evaluate the safety and efficacy of an
      angiotensin receptor blocker (ARB) in controlling blood pressure (BP) in the
      community setting, 703 practitioners recruited 2705 hypertensive patients. There
      were three groups: untreated at the time of study entry with uncontrolled BP
      (>/=140/90 mm Hg) (N = 1957); treated but uncontrolled on current monotherapy (N
      = 685); and treated and controlled, but with unacceptable side effects (N = 63).
      After stopping any previous treatment, patients received telmisartan (40 mg
      daily) for 2 weeks; the dose was increased to 80 mg if BP remained >/=130/85 mm
      Hg. Participants were then followed for a further 4 weeks. Blood pressure
      decreased by 18.9/12.3 mm Hg in the untreated group, by 13.1/7.9 mm Hg in the
      previously treated but uncontrolled group, and increased slightly by 3.5/1.3 mm
      Hg in the previously controlled group. Patients not responding adequately to the
      40-mg telmisartan dose had an initial BP reduction of 7.3/4.5 mm Hg; titration to
      80 mg gave an additional 7.5/5.0 mm Hg reduction and controlled BP (<140/90 mm
      Hg) in 44% of these titrated patients. Overall, control occurred in 56% of white
      patients; 52% of black patients (who responded well to dose titration); 60% of
      patients <65 years; and 46% of patients >/=65 years. Thus, in contrast with the
      relatively flat dose response effects in controlled parallel group trials, this
      practice-based trial has demonstrated the value of titrating telmisartan to its
      maximum dose in patients with inadequate BP responses to the initial dose, and
      has shown its efficacy across major demographic groups.

PMID- 12799095
TI  - The vascular impact of aging and vasoactive drugs: comparison of two digital
      volume pulse measurements.
AB  - BACKGROUND: Indices of pressure wave reflection (RI(DVP)) and large artery
      stiffness (SI(DVP)) can be derived from the digital volume pulse (DVP). Indices
      obtained from the second derivative of the DVP have also been proposed to
      characterize vascular aging and effects of vasoactive drugs. METHODS: We compared
      RI(DVP) and SI(DVP) with the indices a/b, a/c, a/d, and a/e calculated from
      sequential peaks of the second derivative of the DVP in 124 healthy men. The DVP
      was obtained by measuring infrared light transmission through the finger. In 10
      men measurements were obtained at baseline and during intravenous infusion of
      glyceryl trinitrate (GTN, 3 to 300 microg/min) and, on separate occasions,
      angiotensin II (AII, 75 to 300 microg/min) and saline vehicle. RESULTS: SI(DVP)
      was strongly associated with age (R = 0.63, P <.001) but little influenced by AII
      or GTN. RI(DVP) was weakly associated with age but showed a consistent dose
      dependent increase during AII and a decrease during GTN. d/a was strongly
      associated with age (R = -0.66, P <.001), influenced by vasoactive drugs but did
      not change in a dose-dependent manner during GTN. Other second derivative indices
      were less strongly correlated with age and showed an inconsistent response to
      vasoactive drugs. Within subject standard deviations of SI(DVP) and d/a for
      measurements on different occasions were 2.1 and 5.4 "years of vascular aging"
      respectively. CONCLUSIONS: In healthy men, RI(DVP) may be a more reliable index
      of the effects of vasoactive drugs than d/a. SI(DVP) is similarly associated with
      age as is d/a, but less variable and may thus be a better index of vascular
      aging.

PMID- 12799096
TI  - Age-associated changes in left ventricular diastolic function are related to
      increasing left ventricular mass.
AB  - Isometric exercise (IME) produces significant hemodynamic changes in the
      cardiovascular system. We have used IME to study the effect of age on diastolic
      left ventricular (LV) function in 100 normal volunteers. The E/A ratio (peak
      velocity of early/atrial filling phases), deceleration time (DT), and isovolumic
      relaxation time (IVRT) of the transmitral flow were assessed during
      echocardiography with pulsed-Doppler ultrasound at rest and at peak IME using
      handgrip. LV mass index (LVMI) and LV ejection fraction (LVEF) were also
      calculated. Both E/A and IVRT reduced significantly with increasing age. The LVEF
      decreased (P <.0001), whereas LVMI increased (P <.05) with advancing age. The
      LVEF was inversely related to LVMI (P <.05). An inverse relationship was noted
      between E/A and LVMI (P <.01) during IME. The contribution of the atrial
      contraction to the total diastolic flow increased significantly with advancing
      age (P <.02) and increased from 0.29 +/- 0.04 at rest to 0.34 +/- 0.08 during IME
      (P <.0001). It is concluded that with progressing age, the left ventricle becomes
      stiffer resulting in a reduction in early filling and a compensatory increase in
      flow due to atrial contraction. A progressive increase in LVMI, which accompanies
      aging may contribute to stiffening of the left ventricle and deterioration in
      diastolic function of the left ventricle. This is exaggerated by IME.

PMID- 12799097
TI  - Characterization of different high molecular weight angiotensinogen forms.
AB  - BACKGROUND: Angiotensinogen is the substrate for renin in the system that
      releases angiotensin II. This renin-angiotensin system is an important regulator
      of blood pressure (BP), and defects in the system are linked to the development
      of hypertension. Native angiotensinogen is a 62,000-dalton monomer, but various
      high molecular weight forms also exist, which have not been well characterized.
      High molecular weight angiotensinogen has been reported to be 5% of the total
      angiotensinogen, and increases to 60% of the total during pregnancy and
      hypertension. The purpose of this investigation was to study high molecular
      weight angiotensinogen in normal plasma. METHODS: Normal human plasma was run on
      a gel filtration column, and high molecular weight angiotensinogen detected by
      Western blotting. Further purification was by ion-exchange chromatography. In
      vitro polymerization of angiotensinogen was analyzed by sodium dodecyl sulfate
      (SDS) and native gels. RESULTS: Two forms of high molecular weight
      angiotensinogen were found with molecular weights of 500,000 and 250,000 daltons
      on gel filtration, and 140,000 and 110,000 daltons, respectively, on nonreduced
      SDS-polyacrylamide gel electrophoresis, and at 62,000 daltons on reduced gels.
      Our estimation of the amount of high molecular weight angiotensinogen present is
      close to that reported previously. We also describe some of the in vitro
      polymerization characteristics of angiotensinogen, which can be explained by
      angiotensinogen being a member of the serpin family of proteins. CONCLUSIONS: The
      angiotensinogen polymers produced in vitro might provide a model system for some
      of the high molecular weight forms produced in vivo, and help in understanding
      their function.

PMID- 12799098
TI  - Nonpharmacologic treatment of resistant hypertensives by device-guided slow
      breathing exercises.
AB  - BACKGROUND: Recent studies have demonstrated the antihypertensive effect of slow
      breathing exercises, guided interactively by a device, in patients with
      uncontrolled blood pressure (BP) without changing medication. This study examined
      the response to the same treatment protocol in resistant hypertensives. METHODS:
      Seventeen resistant hypertensives exercised device-guided slow breathing for 8
      weeks, 15 min daily, and self-monitored BP. Data stored in the devices were
      collected on a PC-based system. Clinical outcomes were office and home BP changes
      from baseline to end values. RESULTS: Significant reductions in both office BP (
      12.9/-6.9 mm Hg, P <.001 and home BP (-6.4/-2.6 mm Hg, P <.01/P <.05) without
      side effects with 82% responders and good compliance. CONCLUSIONS: Resistant
      hypertensives can benefit from and are compliant with self-treatment by device
      guided slow breathing.

PMID- 12799099
TI  - Development of structural vascular changes in salt-fed rats.
AB  - The hypothesis that long-term administration of a physiologically relevant high
      salt diet to rats leads to the development of structural vascular changes that
      predispose to hypertension was tested. Adult male Sprague-Dawley rats were fed 2%
      NaCl diet for 3 or 6 months; rats fed 0.7% NaCl diet were controls. Then, the
      systemic circulation of the rats was perfusion-fixed at 100 mm Hg. The junction
      of the mesentery and small intestine, the renal cortex, and segments of left
      carotid artery, thoracic aorta, and second order mesenteric arteries were
      embedded in paraffin or epoxy for morphometric measurements. The average monthly
      tail systolic blood pressure (BP) of salt-fed rats at 3 and 6 months were
      unchanged. The following morphometric changes in salt-fed rats were observed: 1)
      dilatation of the carotid artery at 3 months (P <.05); 2) dilatation and reduced
      wall-to-lumen ratio of the second order mesenteric artery (P <.01); 3) increased
      wall-to-lumen ratio of small mesenteric resistance arteries (P <.01); 4) reduced
      wall-to-lumen ratio of renal cortical resistance arteries at 6 months (P <. 05);
      and 5) unchanged structure of aorta. The long-term administration of a high salt
      diet leads to structural vascular changes in normotensive rats. There are
      important regional and segmental variations in the long-term adaptation of
      arteries to a high salt diet.

PMID- 12799100
TI  - Use of an automated blood pressure recording device, the BpTRU, to reduce the
      "white coat effect" in routine practice.
AB  - BACKGROUND: Patients often exhibit higher blood pressure (BP) readings in the
      doctor's office, a phenomenon known as the white coat effect. This study examines
      the presence of a physician in the examining room as a possible factor in
      provoking a white coat effect. METHODS: Blood pressure measurements taken by an
      automated BP recording device, the BpTRU (VSM MedTech Ltd., Vancouver, BC,
      Canada) with the patient alone in the examining room, were compared with the
      following: (1) BP taken by the patient's family physician; (2) BP taken on the
      first visit to a hypertension specialist; (3) BP measured by a trained research
      technician and (4) the mean awake ambulatory BP (ABP). The BpTRU and trained
      research technician readings were taken outside of the office (treatment) setting
      in an ABP research unit. RESULTS: Blood pressure readings (mm Hg, mean +/- SEM)
      taken by the BpTRU (155 +/- 5/88 +/- 2) tended to be lower than for the family
      physician (166 +/- 4/89 +/- 3) and the hypertension specialist (174 +/- 5/92 +/-
      2; P <.001). However, BP taken by the trained research technician (158 +/- 4/90
      +/- 2) was similar to the value obtained by the BpTRU. The mean awake ABP was
      lower (P < 0.01) than the other four BP values. CONCLUSIONS: Use of an automated
      BP recording device outside of the office (treatment) setting can partly
      eliminate the white coat effect. A similar finding was observed with readings
      taken by a trained research technician under similar conditions. Referral of
      patients to nonoffice settings for automated BP recordings may provide a more
      accurate estimate of a patient's BP status, with partial elimination of the white
      coat effect associated with readings taken by a physician.

PMID- 12799101
TI  - Relationships between ambulatory white coat effect and left ventricular mass in
      arterial hypertension.
AB  - The aim of our study was to analyze, in a group of 296 essential hypertensives,
      the relationship between left ventricular mass (LVM) and ambulatory white coat
      effect (WCE); that is the difference between the elevation of the first
      measurements of ambulatory blood pressure monitoring and the mean daytime
      pressure. The study population was separated into two groups according to the
      median of the WCE. The LVM was greater in the groups with higher systolic and
      diastolic ambulatory WCE. The significant association between ambulatory WCE and
      LVM was confirmed by the results of multiple regression analysis, suggesting that
      ambulatory WCE may not be an innocent phenomenon.

PMID- 12799102
TI  - Hormone replacement therapy improves membrane fluidity of erythrocytes in
      postmenopausal women: an electron paramagnetic resonance investigation.
AB  - BACKGROUND: Many studies have shown that hormone replacement therapy (HRT) might
      provide protection against the development of hypertension and arteriosclerosis
      in postmenopausal women. However, the precise mechanism underlying its benefits
      is unclear. This question was addressed in an electron spin resonance (EPR) study
      of membrane function of erythrocytes in postmenopausal women. The purpose of this
      study was to investigate the effects of HRT on membrane fluidity of erythrocytes
      in postmenopausal women by means of the EPR and spin-labeling method. METHODS:
      The healthy postmenopausal women were randomly divided into the HRT group (n =
      14) receiving the conjugated estrogen with medroxyprogesterone for 3 months and
      the non-HRT control group (n = 14). We measured membrane fluidity of erythrocytes
      in postmenopausal women before and after the trial period. RESULTS: The HRT group
      showed a significant decrease in blood pressure (BP) after treatment (systolic BP
      145.7 +/- 5.5 v 123.3 +/- 5.1 mm Hg, n = 14, mean +/- SEM, P <.05). The order
      parameter (S) for 5-nitroxide stearate in the EPR spectra of erythrocyte
      membranes decreased significantly in the HRT group (S: 0.718 +/- 0.002 v 0.695 +/
      0.002, n = 14, P <.01). The finding indicated that HRT increased the membrane
      fluidity of erythrocytes and improved the microviscosity of the cell membranes in
      postmenopausal women. CONCLUSIONS: These results are consistent with the
      hypothesis that HRT might have a beneficial effect on the membrane rheologic
      behavior of erythrocytes and the microcirculation in postmenopausal women.

PMID- 12799103
TI  - Academic detailing to improve antihypertensive prescribing patterns.
AB  - Several studies indicate that treatment of hypertension in the United States does
      not follow recommendations from expert bodies. We thus implemented a program
      using academic detailers to increase practitioner compliance with
      antihypertensive treatment guidelines. Five Veterans Affairs medical facilities
      including academic medical centers and community based outpatient clinics were
      chosen for the intervention. Pharmacists were trained as academic detailers, and
      the intervention included lectures, educational materials, provider profiling,
      and meetings with 25 to 50 providers each. After intervention, the proportion of
      hypertensives receiving calcium antagonists decreased from 43% to 38% (P <.001),
      whereas the proportion receiving a beta blocker or thiazide diuretic increased
      from 58% to 64% (P <.001). For hypertensive subjects with diabetes mellitus or
      congestive heart failure, the proportion receiving an angiotensin converting
      enzyme inhibitor or angiotensin receptor blocker increased from 72% to 76% for
      the former and from 74% to 78% for the latter (P <.001 for both). Among
      hypertensive subjects with coronary artery disease an increase in beta blocker
      use was noted after intervention (P <.001 for change from baseline). Prescribing
      patterns after academic detailing more closely followed national recommendations.

PMID- 12799104
TI  - ALLHAT and beyond.

PMID- 12799105
TI  - Flow cytometric detection of DNA cell cycle alterations in hemocytes of mussels
      (Mytilus galloprovincialis) off the Adriatic coast, Croatia.
AB  - Studies were carried out to determine the alteration in DNA cell cycle
      characteristics of hemocytes of the mussel Mytilus galloprovincialis collected at
      17 different locations (146 individuals) along the Adriatic coast, Croatia. In
      order to connect possible genomic manifestation to urban and/or industrial waste
      flow cytometry was used. We studied incidence of altered DNA profile reflective
      of chromosomal fragmentation phenomena or aneuploid mosaicism, coefficient of
      variation (CV) in DNA fluorescence as a measure of intraindividual genome size
      variability and DNA index (DI) as a measure of ploidy. The different classes of
      DNA cell cycle alterations found in this study mirror either acute or cumulative
      genotoxic effects of the surrounding environment on mussel hemocyte DNA. These
      are intraindividual genome size variability (CV>8, seven individuals from four
      sites), aneuploidy (altered DNA profile and DI<0.9, 45 individuals from 14 sites)
      and accidental apoptotic processes (altered DNA profile and presence of apoptotic
      cells, two individuals from two sites). Normal cell cycle DNA profiles were
      obtained for 89 (60.9%) individuals from all 17 sites and for 146 examined
      samples polyploids were absent. Flow cytometry proved to be a powerful technique
      for the determination of alterations in cell cycle characteristics in mussel
      hemocyte DNA. Therefore, it may be used in pollution control measurements to
      distinguish affected or vulnerable populations from healthy populations living in
      the presence of a wide variety of marine environmental contaminants.

PMID- 12799107
TI  - Effect of cadmium on gonadogenesis and metamorphosis in Pleurodeles waltl
      (urodele amphibian).
AB  - In the amphibian Pleurodeles waltl, steroid hormones play a key role in sex
      differentiation. Since cadmium has been reported to block receptors of sex
      steroid hormones, we analyzed the effects of this heavy metal on Pleurodeles
      larvae gonadogenesis. At stage 42, larvae die in the presence of 10.9 microM Cd
      in the rearing tap water, with TL(50) of 46.3 h, but the concentration of 5.5
      microM is tolerated for more than 60 days. When used at 5.5 microM cadmium
      accumulation measured by atomic absorption spectrophotometry (AAS) in total
      homogenates of larvae at stage 54 (after 77 days of exposure to the heavy metal)
      reached 58.1 microg/g of dry weight. At stage 54, we did not detect inhibitory
      effects on gonadogenesis in larvae reared in the presence of 5.5 microM Cd since
      stage 42. When the exposure to 5.5 microM Cd was lengthened after stage 54,
      metamorphosis was delayed and could not be completed. When larvae were exposed to
      10.9 microM Cd from stage 54, metamorphosis did not occur and gonad development
      was stopped. Our study demonstrates a lack of a direct effect of cadmium on sex
      determination-differentiation but a strong inhibitory effect on metamorphosis,
      which impairs further gonadal development.

PMID- 12799106
TI  - Induction of glutathione-S-transferases in primary cultured digestive gland acini
      from the mollusk bivalve Pecten maximus (L.): application of a new cellular model
      in biomonitoring studies.
AB  - In the last three decades, marine invertebrates have been used to monitor
      environmental health conditions and potential pollution, e.g. in the Mussel Watch
      Program. The whole animal or specific organs are used to determine contamination
      levels and disturbances. In the present study, a new in vitro cell culture model
      was validated for pollution monitoring. A commercial species, the scallop Pecten
      maximus, was tested for the presence and induction of phase II glutathione-S
      transferase (GST) enzymes. These activities were monitored for a year, and the
      results were found to be consistent with those in the literature. Tributyltin,
      ethylmethane sulfonate and the water-soluble fraction of crude oil were assayed
      in, in vitro induction studies. A rapid increase of GST activities was observed
      within 24 h with all compounds tested, and a time- as well as a dose-response was
      established. This in vitro cell culture model seems suitable for routine use to
      predict the effects of pollutants on whole organisms within an ecosystem and in
      fisheries.

PMID- 12799108
TI  - Inhibition of molting by cadmium in the crab Chasmagnathus granulata (Decapoda
      Brachyura).
AB  - The effect of cadmium on molting of the estuarine crab Chasmagnathus granulata
      was assayed. Adult males were eyestalk-ablated, in order to synchronically induce
      molting, and were then chronically exposed to cadmium at 0.25 or 0.50 mg/l. At
      the highest concentration, a significant mortality was detected at the time of
      molting, in the few crabs that could reach the E stage. However, most of the
      crabs exposed from the beginning of the premolt period (D(0) stage) to 0.50 mg/l
      of cadmium were arrested at the D(1)" stage. This effect was not seen when crabs
      were exposed to the same cadmium concentration from either D(1)"' or D(3) premolt
      stages. Crabs arrested by cadmium did not present any difference in the calcium
      content of carapace, compared to controls, while ecdysteroid levels of those
      crabs were similar to the ones of control crabs that were in the same premolt
      stage but could finally molt. These results suggest that cadmium could be
      preventing the normal peaking of ecdysteroids needed for molting. Since eyestalk
      ablated crabs were used, a presumably direct effect of cadmium on Y-organ seems
      likely, by affecting cytoplasmatic calcium concentration and/or other actions.

PMID- 12799109
TI  - Contrasting effects of organic and inorganic toxicants on freshwater periphyton.
AB  - This study analyses the factors influencing the response of periphyton
      communities to toxicants in order to test the validity of the short-term
      physiological method. The effects of two model compounds, atrazine and zinc, on
      the photosynthesis of periphyton from different lotic systems were analyzed using
      short-term toxicity tests. Periphyton communities from seven sites belonging to a
      relatively small area were used to explore the ecological parameters affecting
      toxicity in flowing waters. Furthermore, time course studies of zinc toxicity on
      intact and suspended periphyton were carried out in order to evaluate the
      significance of periphyton structure (thickness) on toxicity. Atrazine toxicity
      varied slightly (0.42-2.42 microM) in tests with photosynthesis as an endpoint.
      Only environmental light was detected to lead to systematic changes in
      sensitivity of field collected communities. In contrast, the range of EC(10)
      values for zinc was very broad (7->1000 microM), and mainly related to algal
      biomass, while also water chemistry (alkalinity) was important. The results of
      time-course experiments indicated that the penetration of zinc into thick
      biofilms was limited. The model compounds tested in the present study may
      exemplify two different situations. In the case of atrazine, the effect on
      periphyton is easy to predict from the physiological tests used here. On the
      other hand, zinc toxicity assessed using photosynthesis of periphyton is much
      affected by many biological and chemical variables. It is concluded that toxicity
      tests of metals and other organic and inorganic compounds should be based on
      longer times of exposure.

PMID- 12799110
TI  - Effects of anesthesia (tricaine methanesulfonate, MS222) on liver
      biotransformation in rainbow trout (Oncorhynchus mykiss).
AB  - The effect of tricaine methanesulfonate (MS222) on rainbow trout liver
      biotransformation rates was investigated with a microsomal model; an in vitro
      preparation that can be employed with or without the use of an anaesthetic. Two
      experimental sets of rainbow trout microsomes were tested; one representing in
      vivo or surgical tricaine exposures and the other representing in vitro
      tissue/organ collection tricaine exposures. Microsomal incubations were performed
      on these two experimental groups with phenol as substrate to assess the effects
      of tricaine on Phase I (ring-hydroxylation) and II (glucuronidation) liver
      biotransformation by monitoring production of hydroquinone (HQ), catechol (CAT),
      and phenylglucuronide (PG). The use of a 2-h 100 mg/l exposure of tricaine for
      surgical anesthesia with or without 24-h recovery did not significantly (P< or
      =0.05) affect rates of phenol (Phase I and II) biotransformation rates; nor, did
      the 5-min 300 mg/l tricaine exposure for isolated organ/tissue collection
      significantly (P< or =0.05) affect phenol (Phase I and II) biotransformation
      rates. There were also no significant statistical differences (P< or =0.05) in
      P450 protein levels, or 7-ethoxyresorufin-O-deethylase (EROD) activity in these
      microsomal assays between any of the tricaine treated rainbow trout and controls.

PMID- 12799111
TI  - Steady-state distribution of metals among metallothionein and other cytosolic
      ligands and links to cytotoxicity in bivalves living along a polymetallic
      gradient.
AB  - The present study was designed to assess the environmental effects of metals in a
      field setting. We explored exposure-->bioaccumulation-->effects relationships in
      freshwater molluscs exposed to metals in their natural habitat. Indigenous
      floater mussels (Pyganodon grandis) were collected from ten limnologically
      similar lakes located along a Cd, Cu and Zn gradient. Ambient free-metal ion
      concentrations were estimated as a measure of metal exposure. Metallothionein
      (MT) was measured in mussel gills and metal partitioning among the various
      cytosolic protein pools was determined by size exclusion chromatography. Various
      biomarkers were also measured, including malondialdehyde (MDA) concentrations in
      the gills and in the digestive gland, glutathione-peroxidase and glutathione
      reductase activities in the digestive gland, and lipid concentrations in the
      gonad. Cadmium and MT concentrations in the gill cytosol increased along the
      contamination gradient, but Cu and Zn levels were independent of the ambient free
      metal ion concentrations. The distribution of Cd among the various cytosolic
      complexes remained quite constant: 80% in the MT-like pool, 7% in the low
      molecular weight pool (LMW<1.8 kDa) and 13% in the high molecular weight pool
      (HMW>18 kDa). For these chronically exposed molluscs there was thus no threshold
      exposure concentration above which spillover of Cd occurred from the MT pool to
      other cytosolic ligands. However, the presence of Cd in the LMW and HMW fractions
      suggests that metal detoxification was imperfect, i.e. that P. grandis was
      subject to some Cd-related stress at low chronic exposure concentrations.
      Consistent with this suggestion, MDA concentrations, an indicator of oxidative
      stress, increased with gill cytosolic Cd. In the digestive gland, MDA
      concentrations were unrelated to any of the measured metals, but glutathione
      peroxidase and glutathione-reductase activities increased with gill cytosolic
      copper. We speculate that cytosolic Cu catalyses the production of reactive
      oxygen species, to which the organism reacts by increasing activities of the two
      enzymes, thus preventing the accumulation of reactive oxygen species. Lipid
      concentrations in the gonad did not decrease with any of the measured
      toxicological parameters, suggesting that energy reserves for reproduction were
      not compromised in the metal-contaminated mussels. The results of the present
      study, where chronically exposed bivalves were collected from their natural
      habitat along a metal contamination gradient, contrast markedly with what would
      have been predicted on the basis of experimental metal exposures, and clearly
      demonstrate the need to study metal exposure-->bioaccumulation-->effects
      relationships in natural populations.

PMID- 12799112
TI  - Physiological responses of Gracilariopsis longissima (S.G. Gmelin) Steentoft,
      L.M. Irvine and Farnham (Rhodophyceae) to sub-lethal copper concentrations.
AB  - Through a series of comparative experiments the relative effects of copper (Cu)
      exposure on the growth and physiology (chlorophyll fluorescence, ion leakage,
      O(2) evolution and pigmentation) of the red seaweed Gracilariopsis longissima was
      investigated. Of the various physiological end-points measured, growth proved to
      be the most sensitive with reductions in relative growth rate (RGR) observed at a
      concentration of 12.5 microg l(-1) Cu, with zero growth above about 300 microg l(
      1). A significant increase in ion leakage and reduction in phycobiliprotein
      concentrations were evident, but only at the highest concentration tested (500
      microg l(-1)), at which point shrinkage of apical tips also occurred.
      Photosynthetic rates, as measured by chlorophyll fluorescence and oxygen
      evolution, were first impaired at 250 microg l(-1), with a 30% reduction in
      photosynthetic efficiency (F(v)/F(m)) and a 60% reduction in oxygen evolution.
      There were no discernible effects on respiration rates or chlorophyll a and beta
      carotene content over this concentration range. It was hypothesised that the
      observed uncoupling of growth and photosynthesis at low Cu concentrations might
      be explained by the release of dissolved organic matter (DOC), resulting in less
      available energy for growth. No such increase in DOC was apparent. Alternative
      explanations to account for the uncoupling, including the diversion of energy for
      maintenance of cell integrity and induction of protective mechanisms, are
      discussed.

PMID- 12799113
TI  - Ionoregulatory disruption as the acute toxic mechanism for lead in the rainbow
      trout (Oncorhynchus mykiss).
AB  - The mechanism for acute toxicity of lead (Pb) in rainbow trout (Oncorhynchus
      mykiss) was investigated at Pb concentrations close to the 96 h LC50 of 1.0 mg
      dissolved Pb l(-1) (0.8-1.4, 95% C.I.) determined in dechlorinated Hamilton city
      tap water (from Lake Ontario, hardness=140 mg l(-1) CaCO(3)). Tissue Pb
      accumulation associated with death was highest in the gill, followed by kidney
      and liver. Significant ionoregulatory impacts were observed in adult rainbow
      trout (200-300 g) fitted with indwelling dorsal aortic catheters and exposed to
      1.1+/-0.04 mg dissolved Pb l(-1). Decreased plasma [Ca(2+)], [Na(+)] and [Cl(-)]
      occurred after 48 h of exposure through to 120 h, with increases in plasma
      [Mg(2+)], ammonia, and cortisol. No marked changes in PaO(2), PaCO(2), pH,
      glucose, or hematological parameters were evident. Branchial Na(+)/K(+) ATPase
      activity in juvenile trout exposed to concentrations close to the 96 h LC50 was
      inhibited by approximately 40% after 48 h of Pb exposure. Calcium ion flux
      measurements using 45Ca as a radiotracer showed 65% inhibition of Ca(2+) influx
      after 0, 12, 24 or 48 h exposure to the 96 h LC50 concentration of Pb. There was
      also significant inhibition (40-50%) of both Na(+) and Cl(-) uptake, measured
      with 22Na and 36Cl simultaneously. We conclude that the mechanism of acute
      toxicity for Pb in rainbow trout occurs by ionoregulatory disruption rather than
      respiratory or acid/base distress at Pb concentrations close to the 96 h LC50 in
      moderately hard water.

PMID- 12799114
TI  - Characterization of lipid in mature enamel using confocal laser scanning
      microscopy.
AB  - OBJECTIVE: To characterize the lipid components of organic matrix in mature human
      enamel using Confocal Laser Scanning Microscopy (CLSM) coupled with a hydrophobic
      fluorescent probe. METHODS: Twenty-four longitudinal sections of human enamel
      were fixed with 3.7% paraformaldehyde (PFA), partially decalcified with 0.5 M of
      EDTA, and labelled with a fluorescent probe (Nile red) before CLSM
      characterization. Based on the fluorescence spectra of Nile red in ethanol (1
      microgram/ml), each enamel section was evaluated with 543 nm light source and
      with 590 nm long pass filter. Spectrophotometric analysis was carried out to
      characterize the autofluorescence and Nile red lipid fluorescence in mature
      enamel. Special optical parameters of the microscope were chosen to rule out the
      intrinsic fluorescence of the samples, and that induced by PFA. RESULTS: The
      intensity of autofluorescence and PFA-induced fluorescence were negligible above
      565 nm; whereas the fluorescence of Nile red peaked at around 600 nm. Lipid
      material was identified in the cross-striations, the lines of Retzius, the Hunter
      Schreger bands, inter-prismatic spaces, and inter-prismatic spaces in the mature
      human enamel. CONCLUSIONS: This technique successfully revealed the distribution
      of lipid components of organic matrix in mature human enamel and may be promising
      in assessing the changes of enamel organic elements in the developmental,
      pathological or experimental conditions.

PMID- 12799115
TI  - The erosive potential of commercially available mouthrinses on enamel as measured
      by Quantitative Light-induced Fluorescence (QLF).
AB  - DESIGN: Longitudinal in vitro. METHODS: Previously extracted, caries free, human
      premolars were selected and prepared by gentle pumicing and coating in an acid
      resistant nail-varnish save for an exposed enamel window on the buccal surface.
      Each was assigned to one of eight groups (six per group, 10 in positive control);
      positive control (citric acid, pH 2.7, F(-) 0 ppm), negative control (pH 7.0, F(
      ) 0 ppm) Listerine (pH 3.87, F(-) 0.021 ppm), Tesco Value (pH 6.05, F(-) 289.00
      ppm), Tesco Total Care (pH 6.20, F(-) 313.84 ppm), Sainsbury's (pH 6.15, F(-)
      365.75 ppm), Sensodyne (pH 6.12, F(-) 285.30 ppm) and Corsodyl (pH 5.65, F(-) 0
      ppm). The titratable acid values (TAV) for each rinse were established using
      volume (ml) of 0.1 M NaOH to achieve pH 7. Fluoride values were obtained by ion
      selective electrode. The solutions were kept at 37 degrees C and gently agitated.
      Teeth were removed at hourly intervals for 15 h, air-dried and subjected to
      Quantitative Light-induced Fluorescence (QLF) examination by a blinded examiner
      and DeltaQ values recorded. At the conclusion of the study each of the positive
      control teeth and one from each other group were sectioned through the eroded
      lesion, ground and polished to 100 micrometers and subjected to transverse
      microradiography and DeltaZ recorded for validation. RESULTS: TAVs were:
      Listerine 2.45 L > Sainsbury's 0.35 ml >Tesco Total Care 0.14 ml > Tesco Value
      0.08 ml > Corsodyl 0.10 ml >Sensodyne 0.9 ml. DeltaQ increased over time for the
      positive control, (0 h 0.2, 10 h 95.2, 15 h 152.3). Negative controls remained
      stable. The increase in DeltaQ for each rinse after 15 h was Listerine (9.3(+/
      7.2)), Corsodyl (1.5(+/-1.2)), Tesco Value (1.8(+/-1.2)), Tesco Total Care
      (1.4(+/-1.1)), Sainsbury's (3.4(+/-2.2)), Sensodyne (0.9(+/-1.6)). TMR confirmed
      the presence/absence of erosive lesions. CONCLUSIONS: QLF effectively monitored
      erosion in the positive controls and lack of erosion in the NC. Only one
      mouthrinse (Listerine) caused any erosion compared to the negative control, but
      this was only significant after 14 h of continuous use.

PMID- 12799116
TI  - Shear bond strength of AH-26 root canal sealer to dentine using three dentine
      bonding agents.
AB  - OBJECTIVE: The purpose of the study was to compare the bond strength of AH-26
      root canal sealer to human root canal dentine exposed to different intracanal
      medications both with and without the use of three bonding agents. The materials
      used were AH-26 sealer, two one-bottle bonding agents (Single Bond, Bond-1) and
      one self-etching bonding agent (Clearfill SE Bond). METHODS: The dentine
      substrate was obtained from single rooted human teeth. The dentine specimens were
      treated either with EDTA 15% or phosphoric acid 37% to achieve the removal of
      smear layer. The AH-26 sealer was placed on the dentine surfaces both with and
      without the use of the bonding agents. Bond strength was tested using a single
      plane shear test assembly. RESULTS: The SBS values were (MPa): Group A (EDTA-AH
      26) 3.678+/-0.853, Group B (Phosphoric acid-AH-26) 3.470+/-0.834, Group C (EDTA
      Single Bond-AH-26) 4.8+/-0.865, Group D (Phosphoric acid-Single Bond-AH-26)
      5.043+/-1.022, Group E (EDTA-Bond 1-AH-26) 4.939+/-0.877, Group F (Phosphoric
      acid-Bond 1-AH-26) 5.101+/-1.117, Group G (Clearfill SE Bond-AH-26) 6.975+/
      1.694. The use of dentine bonding agents improved significantly (p<0.05) the
      adhesion of AH-26 sealer with the root canal dentine. However, the best results
      were obtained with the self-etching system. Similar results were observed from
      the pretreatment of dentine either with phosphoric acid 35% or EDTA 15%.
      CONCLUSIONS: The use of dentine bonding agents gave higher shear bond strengths
      of AH-26 sealer to human root canal dentine.

PMID- 12799117
TI  - A study to assess the effects of a new detergent-free, olive oil formulation
      dentifrice in vitro and in vivo.
AB  - OBJECTIVE: To determine the effects of a detergent-free dentifrice containing
      olive oil using in vitro microbiological tests and an in vivo plaque re-growth
      model. METHOD: A total of 20 subjects took part in a double blind, single-centre,
      crossover study in which slurry rinses were the only form of plaque control over
      a 5-day period. Following a washout and prophylaxis the subjects used 2x daily
      rinses in the absence of all other plaque control methods. Subjects returned to
      the clinic on the afternoon of day 5 when plaque was disclosed and assessed by
      plaque index and area. A further 9-day washout was carried out and the rinse
      period repeated to ensure that each subject had used both experimental and
      control slurries. In vitro microbiological experiments were conducted to examine
      the effects of olive oil alone and in the new dentifrice on bacterial growth and
      adhesion. RESULTS: 20 subjects completed the trial. The olive oil product showed
      a significant inhibition of plaque re-growth (17.2%) compared with a fluoride
      matched control using the Turesky index (p<0.0001) and also using the planimetric
      technique (22.0%) (p<0.0001). Significant decreases in bacterial growth and
      adhesion (measured as total viable count) were detected in the presence of olive
      oil and the new dentifrice. CONCLUSION: The results suggest that the experimental
      olive oil containing paste has potential value in the inhibition of plaque.

PMID- 12799118
TI  - PCR methodology as a valuable tool for identification of endodontic pathogens.
AB  - OBJECTIVES: This paper reviews the principles of polymerase chain reaction (PCR)
      methodology, its application in identification of endodontic pathogens and the
      perspectives regarding the knowledge to be reached with the use of this highly
      sensitive, specific and accurate methodology as a microbial identification test.
      DATA SOURCES: Studies published in the medical, dental and biological literature.
      STUDY SELECTION: Evaluation of published epidemiological studies examining the
      endodontic microbiota through PCR methodology. CONCLUSIONS: PCR technology has
      enabled the detection of bacterial species that are difficult or even impossible
      to culture as well as cultivable bacterial strains showing a phenotypically
      divergent or convergent behaviour. Moreover, PCR is more rapid, much more
      sensitive, and more accurate when compared with culture. Its use in endodontics
      to investigate the microbiota associated with infected root canals has expanded
      the knowledge on the bacteria involved in the pathogenesis of periradicular
      diseases. For instance, Tannerella forsythensis (formerly Bacteroides forsythus),
      Treponema denticola, other Treponema species, Dialister pneumosintes, and
      Prevotella tannerae were detected in infected root canals for the first time and
      in high prevalence when using PCR analysis. The diversity of endodontic
      microbiota has been demonstrated by studies using PCR amplification, cloning and
      sequencing of the PCR products. Moreover, other fastidious bacterial species,
      such as Porphyromonas endodontalis, Porphyromonas gingivalis and some Eubacterium
      spp., have been reported in endodontic infections at a higher prevalence than
      those reported by culture procedures.

PMID- 12799119
TI  - Monomer conversion versus flexure strength of a novel dental composite.
AB  - OBJECTIVES: To quantify the monomer conversion and flexural strength of an
      experimental oxirane-based composite material (EXL596) compared with two,
      commercially available, dimethacrylate based restoratives (Z250 and Z100).
      METHODS: Fourier-transform infra-red spectroscopy (FTIR) was utilised to evaluate
      the degree of conversion (DC) (n=5) and biaxial flexure strength (BFS) testing
      (n=20) was used to analyse flexural strength and associated Weibull moduli (m) of
      each material following 0.1, 0.5, 1, 4, 24 and 48 h immersion in a lightproof
      waterbath maintained at 37+/-1 degrees C. RESULTS: The DC of Z250 and Z100
      following 0.1, 0.5 and 1 h post-irradiation was significantly greater than the DC
      of EXL596 for the same immersion periods. This was manifested as a significant
      decrease in BFS and associated m of EXL596 compared with Z250 and Z100 for the
      0.1, 0.5 and 1 h post-irradiation periods. The DC and BFS of EXL596 were
      significantly greater than Z250 and Z100 following 24 h immersion. CONCLUSIONS:
      Assessment of FTIR spectra, BFS and associated m has provided a useful method in
      the quantitative analysis of resin-based composite conversion. Identification of
      the decreased DC of EXL596 compared with Z250 and Z100 was achieved using FTIR.
      However, decreased conversion rates within the first hour following irradiation
      of EXL596 may compromise flexural strength properties (associated with a decrease
      in BFS and m) which may be inadequate under masticatory loading.

PMID- 12799120
TI  - The volumetric fraction of inorganic particles and the flexural strength of
      composites for posterior teeth.
AB  - OBJECTIVE: To evaluate the content of inorganic particles and the flexural
      strength of new condensable composites for posterior teeth in comparison to
      hybrid conventional composites. METHOD: The determination of the content of
      inorganic particles was performed by mass weighing of a polymerized composite
      before and after the elimination of the organic phase. The volumetric particle
      content was determined by a practical method based on Archimedes' principle,
      which calculates the volume of the composite and their particles by differential
      mass measured in the air and in water. The flexural strength of three points was
      evaluated according to the norm ISO 4049:1988. RESULTS: The results showed the
      following filler content: Alert, 67.26%; Z-100, 65.27%; Filtek P 60, 62.34%;
      Ariston pHc, 64.07%; Tetric Ceram, 57.22%; Definite, 54.42%; Solitaire, 47.76%.
      In the flexural strength test, the materials presented the following decreasing
      order of resistance: Filtek P 60 (170.02 MPa)>Z-100 (151.34 MPa)>Tetric Ceram
      (126.14 MPa)=Alert (124.89 MPa)>Ariston pHc (102.00 MPa)=Definite (93.63
      MPa)>Solitaire (56.71 MPa). CONCLUSION: New condensable composites for posterior
      teeth present a concentration of inorganic particles similar to those of hybrid
      composites but do not necessarily present higher flexural strength.

PMID- 12799121
TI  - Development of low erosive carbonated fruit drinks 2. Evaluation of an
      experimental carbonated blackcurrant drink compared to a conventional carbonated
      drink.
AB  - OBJECTIVE: Previous studies demonstrated that a non-carbonated blackcurrant juice
      drink with added calcium produced little erosion of enamel in vitro and in situ
      by comparison with other low pH fruit drinks. The aim of this study is to
      evaluate the erosive effects in situ of an experimental formulation carbonated
      drink with added calcium, compared to a conventional carbonated drink over a 20
      day period using a similar design as in previous studies. METHOD: The study was a
      single centre, single blind, randomised placebo controlled three cell crossover
      design involving 15 volunteers. The test drinks were an experimental carbonated
      ready-to-drink (RTD) blackcurrant drink, a conventional carbonated RTD orange
      drink and water. Two enamel samples were retained in situ, in the midline of the
      hard palate on an upper removable acrylic appliance. Drinks were 250 ml volumes
      consumed four times per day during 20 working days. Measurements of enamel loss
      were made on enamel samples after days 2, 5, 10, 15 and 20 by profilometry.
      RESULTS: The experimental carbonated blackcurrant drink caused significantly less
      enamel loss than the conventional carbonated orange drink at all time points
      measured, but was not significantly different from water at days 2, 5 and 20.
      CONCLUSIONS: This study has shown that it is possible to modify carbonated soft
      drinks in a manner similarly shown with non-carbonated soft drinks, to minimise
      dental erosion.

PMID- 12799122
TI  - Effect of sodium nitrite and ascorbic acid on the growth and acid production of
      Streptococcus mutans.
AB  - Nitrite at acid pH has been shown to be antibacterial particularly against the
      highly cariogenic species Streptococcus mutans. Nitrite might yield nitrosamines
      in vivo but ascorbic acid (vitamin C) could counteract these potential ill
      effects. The aim of this study is to determine whether ascorbic acid would
      interfere with the ability of sodium nitrite to suppress growth and acid
      production of S. mutans, NCTC 10449(T) and NCTC 10832. Strains were grown in
      Fastidious Anaerobe Broth before exposure to 200 mM nitrite in the presence of
      various concentrations of ascorbic acid (0.0, 5.7, 11.4, 17.0, 22.7, 28.4, 56.8,
      85.2 mM). End pH was measured after 24 h exposure and cultures were serially
      diluted for viable counts. Statistical significance of differences in end pH
      values, each from 10 experiments, was determined using the Mann-Whitney U-Test.
      At all concentrations of ascorbic acid plus 200 mM nitrite plus S. mutans the pH
      was higher than with controls lacking ascorbic acid and/or nitrite (p>/=0.001).
      S. mutans was viable (between 4.5 x 10 (8) and 7.9 x 10 (9) cfuml (-1)) after
      growth in the presence of ascorbic acid at all concentrations without nitrite,
      whereas it was not detected when 200 mM nitrite was also present. CONCLUSIONS:
      ascorbic acid does not prevent the action of nitrite against S. mutans. Therefore
      ascorbic acid could be used in conjunction with nitrite to help counteract
      potential ill effects for humans.

PMID- 12799123
TI  - Importance of smoking habits for longitudinal and age-matched changes in body
      mass index: a cohort study of Swedish men and women.
AB  - BACKGROUND: Previous longitudinal studies of smoking and BMI have focused on
      smoking cessation. The aim of the present study was to disentangle the effects of
      long-term smoking on longitudinal changes and age-matched BMI differences (time
      period effects) in a nation-wide Swedish cohort. METHODS: Men and women (n =
      4349) ages 18-73 years reported height, weight, and smoking status for a baseline
      survey in 1980-1981. Eight and 16 years after baseline, follow-up surveys were
      conducted for 3244 (75%) of the 4349 subjects. Long-term smokers and long-term
      nonsmokers were compared with respect to longitudinal changes and age-matched BMI
      differences. RESULTS: For middle-age adults, the longitudinal increases in BMI
      were smaller among long-term smokers than long-term nonsmokers regardless of
      gender. Among the elderly, the longitudinal decrease in BMI was greatest among
      long-term smokers. Among men, age-matched BMI differences between surveys were
      smaller for long-term smokers than for nonsmokers. Among women, however, age
      matched BMI differences were greater for long-term smokers than for nonsmokers.
      CONCLUSIONS: In middle-age subjects, longitudinal BMI increases are smaller among
      smokers than nonsmokers. During old age, the BMI of smokers decreases more than
      that of nonsmokers. Unknown factors related to gender contribute to larger time
      period effects of smoking in women than in men.

PMID- 12799124
TI  - Does early physical activity predict body fat change throughout childhood?
AB  - BACKGROUND: Declining levels of physical activity in the population at large may
      be responsible in part for the rising rates of childhood obesity. Studies to
      date, however, have not consistently demonstrated such a protective effect. We
      used longitudinal data from the Framingham Children's Study (FCS) to address this
      important question. METHODS: We used 8 years of activity monitoring (Caltrac
      electronic motion sensors) and repeated anthropometry measures for 103 children
      to examine the effect of activity on body fat change from preschool to early
      adolescence. Longitudinal data analysis methods were employed to account for the
      use of repeated measures on these children. RESULTS: Children in the highest
      tertile of average daily activity from ages 4 to 11 years had consistently
      smaller gains in BMI, triceps, and sum of five skinfolds throughout childhood. By
      early adolescence (age 11), the sum of five skinfolds was 95.1, 94.5, and 74.1
      for the low, middle, and high tertiles of activity, respectively (P for trend =
      0.045). This protective effect of activity was evident for both girls and boys.
      CONCLUSION: This longitudinal study adds strong support for the hypothesis that
      higher levels of physical activity during childhood lead to the acquisition of
      less body fat by the time of early adolescence.

PMID- 12799125
TI  - Indices related to apo CII and CIII serum concentrations and coronary heart
      disease: a case-control study.
AB  - BACKGROUND: Triglycerides (TG) are carried in the circulation by diverse
      lipoprotein particles, which vary in their lipid and protein content, metabolism,
      and atherogenicity. Several indices related to apolipoproteins (apo) CII and CIII
      blood concentration have been proposed to reflect TG metabolism more accurately
      than the blood level of TG. In the present study we compared the distribution of
      those indices in coronary heart disease (CHD) patients and controls.. METHODS:
      Ninety consecutively discharged patients with CHD and 209 healthy controls were
      included in the analysis. Demographic, clinical, and laboratory characteristics
      were obtained. RESULTS: The CHD patients differed appreciably from controls in
      several TG-related variables. After adjusting for cardiovascular risk factors,
      significant associations were found between CHD and the following: TG, VLDL-C,
      apo CIII, apo CIII in HDL, apo CIII in VLDL + LDL, apo CII- to- TG ratio, and apo
      CIII ratio (CIII in HDL/CIII in VLDL + LDL). Further adjustment for HDL-C
      substantially attenuated the above associations, except for those regarding apo
      CIII in VLDL + LDL (odds ratio (OR): 1.69 per 1 SD increment, 95%CI: 1.03-2.77)
      and apo CIII ratio (OR: 0.40 per 1 SD increment, 95%CI: 0.15-1.00). CONCLUSION:
      Our results add to the growing evidence which links apo CIII concentration in
      VLDL + LDL to CHD. Further confirmation in prospective studies would be required
      before considering this measurement as a screening tool.

PMID- 12799126
TI  - Randomized controlled trial of the effects of nurse case manager and community
      health worker interventions on risk factors for diabetes-related complications in
      urban African Americans.
AB  - BACKGROUND: African Americans suffer disproportionately from diabetes
      complications, but little research has focused on how to improve diabetic control
      in this population. There are also few or no data on a combined primary care and
      community-based intervention approach. METHODS: We randomly assigned 186 urban
      African Americans with type 2 diabetes (76% female, mean A SD age 59 A 9 years)
      to 1 of 4 parallel arms: (1) usual care only; (2) usual care + nurse case manager
      (NCM); (3) usual care + community health worker (CHW); (4) usual care + nurse
      case manager/community health worker team. Using the framework of the Precede
      Proceed behavioral model, interventions included patient counseling regarding
      self-care practices and physician reminders. RESULTS: The 2-year follow-up visit
      was completed by 149 individuals (84%). Compared to the Usual care group, the NCM
      group and the CHW group had modest declines in HbA(1c) over 2 years (0.3 and
      0.3%, respectively), and the combined NCM/CHW group had a greater decline in
      HbA(1c) (0.8%. P = 0.137). After adjustment for baseline differences and/or
      follow-up time, the combined NCM/CHW group showed improvements in triglycerides (
      35.5 mg/dl; P = 0.041) and diastolic blood pressure, compared to the usual care
      group (-5.6 mmHg; P = 0.042). CONCLUSIONS: Combined NCM/CHW interventions may
      improve diabetic control in urban African Americans with type 2 diabetes.
      Although results were clinically important, they did not reach statistical
      significance. This approach deserves further attention as a means to reduce the
      excess risk of diabetic complications in African Americans.

PMID- 12799127
TI  - Does methodology affect the ability to monitor tobacco control activities?
      implications for HEDIS and other performance measures.
AB  - BACKGROUND: It is unclear whether methodological differences in sample size,
      survey methods, and analysis approach significantly affect the ability to
      accurately monitor tobacco control activities and to make rate comparisons.
      METHODS: Questionnaires were sent to 64,764 members of nine health plans in
      diverse settings soon after their visit to a primary care clinician. Of these
      41,677 completed responses were received. We compared responses received by mail
      and by telephone follow-up for the percentage of smokers, characteristics of
      smokers, and their rates of reporting physician cessation counseling. RESULTS:
      Overall, 10.2% were current cigarette smokers, but the proportion was 8.6% for
      mail responders and 17.2% for phone follow-up responders. Smokers identified by
      phone follow-up were different from mail responders in most demographic and
      smoking characteristics and their reports of clinical smoking cessation
      activities differed for six of nine clinician smoking cessation actions.
      Calculating advice rates as a proportion of visits produced lower rates with more
      dispersion among plan rates than doing so without accounting for visit variation.
      CONCLUSIONS: Smoking surveys using only mailed questionnaires dramatically
      undersample smokers, especially in some demographic groups. Comparisons of
      tobacco counseling among health plans can be improved by ensuring an adequate
      sample size and response rate and by analyzing by frequency of quit advice.

PMID- 12799128
TI  - New Moves: a school-based obesity prevention program for adolescent girls.
AB  - BACKGROUND: This study tests the feasibility of an innovative school-based
      program for obesity prevention among adolescent girls. New Moves was implemented
      as a multicomponent, girls-only, high-school physical education class. METHODS:
      Six schools were equally randomized into intervention and control conditions.
      Data were collected at baseline, postintervention, and 8-month follow-up to
      assess program impact on physical activity, eating patterns, self-perceptions,
      and body mass index (BMI) among 89 girls in the intervention and 112 girls in the
      control conditions. Program evaluation also included interviews with school
      staff, parent surveys, and participant interviews and process evaluation surveys.
      RESULTS: The feasibility of implementing New Moves was high, as indicated by
      strong satisfaction among participants, parents, and school staff, and by program
      sustainability. Participants perceived a positive program impact on their
      physical activity, eating patterns, and self-image. Girls in the intervention
      significantly progressed in their stage of behavioral change for physical
      activity from baseline to follow-up. However, for the majority of outcome
      variables, differences between intervention and control schools at
      postintervention and follow-up were not statistically significant. CONCLUSIONS:
      New Moves was well received and fills a needed niche within school physical
      education programs. An expanded intervention and evaluation is needed to enhance
      and assess long-term program effectiveness.

PMID- 12799129
TI  - Secular trends in leisure-time physical activity in men and women across four
      decades.
AB  - BACKGROUND: We examined secular trends in leisure-time physical activities (LTPA)
      in health-conscious men (n = 1359) from 1958 to 1998 and in women (n = 839) from
      1978 to 1998, who were participants of the Baltimore Longitudinal Study of Aging
      (BLSA). METHODS: LTPA was the self-reported time spent performing 97 activities,
      and was converted to metabolic equivalent of oxygen uptake (MET) minutes per day.
      Evaluations of LTPA were averaged for each decade. The prevalence of a sedentary
      lifestyle in each decade was assessed based on compliance with widely publicized
      recommendations for participation in physical activity. All analyses were
      adjusted for age, education, and race differences across decades. RESULTS: Median
      high-intensity LTPA, defined as activities >/=6 METs, increased from 30 to 80 MET
      min/day from the 1960s to the 1990s for men (P < 0.01) but did not change between
      the 1970s and the 1990s in women. Moderate-intensity LTPA, defined as 4-5.9 METs,
      did not change significantly over these periods in either sex. The percentage of
      sedentary men, defined as those performing <40 MET min/day of high-intensity
      LTPA, declined across the four decades, whereas for women it did not change
      significantly. CONCLUSIONS: In a health-conscious sample across a broad age
      range, national recommendations appear to have made modest progress in decreasing
      the proportion of sedentary adults.

PMID- 12799130
TI  - Characteristics of physically inactive older adults with arthritis: results of a
      population-based study.
AB  - BACKGROUND: Arthritis is the most prevalent chronic condition among persons age
      65 and older in North America. Physical inactivity in this population is linked
      to functional limitations, increased risk for cardiovascular disease, diminished
      quality of life, and disability. The purpose of this study was to identify risk
      factors for inactivity. METHODS: National data for 6256 community-dwelling older
      adults with arthritis from the 1996-1997 Canadian National Population Health
      Survey were examined using logistic regression analyses. The independent
      variables included sociodemographic characteristics, health status, psychosocial
      factors, health behaviors, and medication use. RESULTS: Inactive persons were
      significantly (P < 0.05) more likely to be women, older (75+), have functional
      limitations, be underweight (BMI < 20) or overweight (BMI > 25), have severe
      pain, or not have prescription drug insurance coverage. The same group was less
      likely to be unmarried, well educated, from western provinces, attend church
      frequently, consume alcohol infrequently, have higher levels of social support,
      have better self-rated health, or use pain medication. CONCLUSIONS: The profile
      presented in this study should be fully considered by health care providers when
      educating patients with arthritis about the adverse health effects of sedentary
      behavior. Prescription drug insurance coverage may facilitate activity among
      elders with arthritis.

PMID- 12799131
TI  - Impact of economic policies on reducing tobacco use among Medicaid clients in New
      York.
AB  - BACKGROUND: New York State (NYS) recently implemented Medicaid coverage for
      prescription pharmacologic adjuncts for cessation and a 55-cent excise tax on a
      pack of cigarettes. This study examined awareness and use of stop smoking
      medications and changes in smoking/purchasing behavior among Medicaid clients.
      METHODS: Participants (n = 173) were English-speaking Medicaid clients ages 18-64
      years who currently smoked cigarettes and volunteered to be interviewed while
      waiting to reregister with the NYC Medicaid Office during early 2001. Data were
      collected using a brief (10-min) interviewer-administered questionnaire. RESULTS:
      Over 80% of Medicaid clients reported some desire to stop smoking and 40%
      intended to stop smoking in the next 6 months. Awareness of Medicaid coverage for
      tobacco cessation pharmacotherapy was 7% for nicotine replacement therapy and 13%
      for bupropion. Use of these stop smoking medications varied across products but
      in general was low (<10%). Half of the Medicaid clients reported changing their
      smoking behavior as a result of the cigarette tax increase. CONCLUSIONS: The
      majority of Medicaid clients report a desire to stop smoking, but these economic
      influences alone are insufficient to substantially reduce smoking in this
      population. These findings emphasize the importance of allocating a portion of
      tobacco tax revenue to promote both expanded awareness of this prescription
      benefit among Medicaid clients and to support programs to further assist low
      income smokers in their attempts to stop smoking.

PMID- 12799132
TI  - Pregnancy planning and vitamin/mineral use during pregnancy: results from a study
      in Portugal.

PMID- 12799133
TI  - Mice lacking Tropomodulin-2 show enhanced long-term potentiation, hyperactivity,
      and deficits in learning and memory.
AB  - Actin filaments control cell morphology and are essential to the growth of
      dendritic spines and the plasticity of hippocampal long-term potentiation (LTP).
      The length of these filaments is regulated in muscle and nonmuscle cell types by
      tropomodulins 1-4 (Tmod1-4), a family of proteins that cap the pointed ends of
      actin filaments. To investigate whether tropomodulins could play a role in
      synaptic plasticity, learning, memory, or behavior, we created mice lacking
      Tropomodulin-2 (Tmod2), which is highly expressed in neuronal structures.
      Tmod2(lacZ-/-) mice are viable and fertile and exhibit no gross morphological or
      anatomical abnormalities, but behavioral analysis found hyperactivity, reduced
      sensorimotor gating, and impaired learning and memory. Electrophysiological
      analysis revealed enhanced LTP in Tmod2(lacZ-/-) mice. These studies suggest that
      Tmod2 plays a role in behavior, learning, memory, and synaptic plasticity.

PMID- 12799135
TI  - Mutant huntingtin increases nuclear corepressor function and enhances ligand
      dependent nuclear hormone receptor activation.
AB  - There is increasing evidence that transcriptional dysregulation is important in
      Huntington's disease pathogenesis. The transcriptional protein, nuclear
      corepressor (NCoR), acts to repress transcription of nuclear hormone receptors,
      such as the thyroid hormone receptor (TR) and retinoic acid receptor, in the
      absence of their appropriate ligand. NCoR has been shown to bind to the mutated
      huntingtin protein in a yeast two-hybrid screen. This aberrant interaction may
      have profound effects on both the function of the NCoR protein and on its control
      of nuclear hormone receptor-mediated transcription. To test this hypothesis,
      reporter gene assays were performed in inducible PC12 cell lines expressing exon
      1 of the human huntingtin protein (Htt) with either a 25 or 103 polyglutamine (Q)
      repeat. Expression of mutant 103Q protein appears to enhance the ability of NCoR
      to repress TR-mediated transcription in the absence of ligand. Western analyses
      indicated that the expression of the mutant 103Q Htt protein did not change the
      endogenous NCoR levels in the HD103Q PC12 cells when compared to uninduced cells.
      Interestingly, using GST pull-down assays we found that a mutant Htt exon 1
      construct with 53 polyglutamine (HD53Q) did not bind to NCoR in a polyglutamine
      dependent fashion. These findings suggest that an aberrant NCoR-Htt interaction
      does not exist in vitro. Expression of the mutant 103Q protein was also found to
      enhance ligand-dependent activation of TR and retinoic acid receptor. In vitro
      binding data shows that TR binds to HD53Q in the presence of ligand. Taken
      together these data suggest that Htt may function as a transcriptional
      coactivator of nuclear hormone receptors.

PMID- 12799134
TI  - Regulation of the myelin gene periaxin provides evidence for Krox-20-independent
      myelin-related signalling in Schwann cells.
AB  - We investigated the role of Krox-20 (Egr2), a transcription factor that regulates
      myelination, in controlling the myelin-associated protein periaxin. In developing
      Schwann cells, periaxin immunoreactivity appeared at least 2 days before Krox-20
      immunopositive nuclei. Consistent with this, in Krox-20 null mice periaxin was
      upregulated on schedule, albeit to a lower level. In culture Krox-20 and periaxin
      were upregulated by cAMP as expected for myelin genes. Only those cells with the
      highest periaxin levels also expressed Krox-20, while other periaxin-positive
      cells remained Krox-20-negative. Furthermore, cAMP elevated periaxin even in Krox
      20 null cells. We also found that in culture enforced Krox-20 expression induced
      expression of periaxin mRNA and protein in the absence of cAMP elevating agents,
      and that this induction was inhibited by the co-repressor NAB2. These findings
      reveal a dual mechanism for periaxin regulation and suggest that the role of Krox
      20 is to amplify an earlier Krox-20-independent activation of the periaxin gene.
      Thus the axonal signals responsible for myelination are only partially transduced
      in Schwann cells by mechanisms that depend on Krox-20.

PMID- 12799136
TI  - Possible involvement of a fibroblast growth factor 9 (FGF9)-FGF receptor-3
      mediated pathway in adult pig retinal ganglion cell survival in vitro.
AB  - The expression and potential roles of fibroblast growth factors (FGF) and their
      cognate FGF receptors (FGFR) in adult mammalian retinal ganglion cells (RGC) are
      poorly known. We show that FGFR-3 and FGFR-4 are especially pronounced on RGC and
      amacrine cell bodies in adult pig inner retinae both in vivo and in vitro.
      Western blotting revealed distinct profiles for each receptor. Expression of each
      FGFR and effects of the preferred ligand for FGFR-3, FGF9, upon RGC survival and
      neurite outgrowth were examined in primary retinal cell cultures: whereas there
      was no stimulation of neuritogenesis, RGC survival was promoted in a dose
      dependent manner (ED(50) approximately 500 pg/ml, mean maximal increase of 60%)
      and could be completely blocked by addition of FGF9 neutralising antibody.
      Experiments with three additional FGF (FGF1, FGF2, and FGF4) showed no
      stimulation of RGC survival above control levels. Taken together, these data
      suggest that the ligand-receptor couple FGF9-FGFR-3 may function to promote
      survival of adult mammalian RGC, and their application might be beneficial in
      retinal degenerative diseases such as glaucoma.

PMID- 12799137
TI  - Integrin antagonists affect growth and pathfinding of ventral motor nerves in the
      trunk of embryonic zebrafish.
AB  - Integrins are thought to be important receptors for extracellular matrix (ECM)
      components on growing axons. Ventral motor axons in the trunk of embryonic
      zebrafish grow in a midsegmental pathway through an environment rich in ECM
      components. To test the role of integrins in this process, integrin antagonists
      (the disintegrin echistatin in native and recombinant form, as well as the Arg
      Gly-Asp-Ser peptide) were injected into embryos just prior to axon outgrowth at
      14-16 h postfertilization (hpf). All integrin antagonists affected growth of
      ventral motor nerves in a similar way and native echistatin was most effective.
      At 24 hpf, when only the three primary motor axons per trunk hemisegment had
      grown out, 80% (16 of 20) of the embryos analyzed had abnormal motor nerves after
      injection of native echistatin, corresponding to 19% (91 of 480) of all nerves.
      At 33 hpf, when secondary motor axons were present in the pathway, 100% of the
      embryos were affected (24 of 24), with 20% of all nerves analyzed (196 of 960)
      being abnormal. Phenotypes comprised abnormal branching (64% of all abnormal
      nerves) and truncations (36% of all abnormal nerves) of ventral motor nerves at
      24 hpf and mostly branching of the nerves at 33 hpf (94% of all abnormal nerves).
      Caudal branches were at least twice as frequent as rostral branches. Surrounding
      trunk tissue and a number of other axon fascicles were apparently not affected by
      the injections. Thus integrin function contributes to both growth and pathfinding
      of axons in ventral motor nerves in the trunk of zebrafish in vivo.

PMID- 12799138
TI  - TIGR is upregulated in the chronic glial scar in response to central nervous
      system injury and inhibits neurite outgrowth.
AB  - Reactive astrocytes respond to central nervous system (CNS) injury and disease by
      elaborating a glial scar that is inhibitory to axonal regeneration. To identify
      genes that may be involved in the astrocytic response to injury, we used
      differential display polymerase chain reaction and an in vivo model of the CNS
      glial scar. Expression of the trabecular meshwork inducible glucocorticoid
      response (TIGR) gene was increased in gliotic tissue compared with the uninjured
      cerebral cortex. Increased TIGR expression by reactive astrocytes was confirmed
      by in situ hybridization, quantitative reverse transcriptase-polymerase chain
      reaction, immunoblot analysis, and immunohistochemistry. Although mutations of
      the TIGR gene have been implicated in glaucoma, a function for TIGR has not been
      reported. Since TIGR is secreted, we assessed a possible role in inhibition of
      neuronal regeneration with an in vitro bioassay and found that this protein is a
      potent inhibitor of neurite outgrowth. Thus, TIGR is a newly identified component
      of the CNS glial scar that is likely to contribute to neuronal regenerative
      failure characteristic of the mammalian CNS.

PMID- 12799139
TI  - Patterning of motor neurons by retinoic acid in the chick embryo hindbrain in
      vitro.
AB  - Motor neurons are found throughout the developing chick hindbrain, while somatic
      motor (SM) neurons develop only in rhombomeres 5 to 8 (r5-8), and in r1. In r2-8
      neuroepithelial explants from stage 7-10 embryos cultured in collagen gels, we
      found that motor neurons were generated throughout r2-8, while SM neuron
      differentiation was restricted to r5-8, as in vivo. Exposure of such explants to
      retinoic acid (RA) resulted in SM neuron differentiation throughout r2-8, while
      inclusion of the mesoderm and endoderm suppressed this effect. In explants with
      mesoderm/endoderm, RA-dependent SM neuron differentiation in rostral rhombomeres
      was restored by the application of an inhibitor of the RA-degrading enzyme CYP26.
      We found that the mesoderm/endoderm (either with or without RA) induced Cyp26
      expression in the neuroepithelium in vitro, suggesting that the modulatory effect
      of CYP26 on RA-dependent patterning might be dependent on local signals.

PMID- 12799140
TI  - Acetylcholinesterase promotes neurite elongation, synapse formation, and surface
      expression of AMPA receptors in hippocampal neurones.
AB  - Here we show that chronic application of low concentrations (0.01-0.05 U/ml) or a
      single application of 1-5 U/ml acetylcholinesterase (AChE) promotes the extension
      of neuronal processes, synapse formation, and alpha-amino-3-hydroxy-5
      methylisoxazolepropionate receptor (AMPAR) surface expression in both embryonic
      and postnatal hippocampal cultures. The total number of AMPARs was unchanged but
      the proportion of receptors that were surface-expressed, predominantly at
      synapses, was approximately doubled following AChE treatment. Blockade of the
      peripheral anionic site of endogenous AChE in the cultures dramatically reduced
      neurite outgrowth but did not alter the appearance of synaptic markers SV2a and
      PSD95. These results indicate that AChE is necessary for normal dendrite and axon
      formation in hippocampal neurones and suggest that it may also play a role in
      excitatory synapse development, plasticity, and remodelling.

PMID- 12799141
TI  - Dlx transcription factors regulate differentiation of dopaminergic neurons of the
      ventral thalamus.
AB  - Recent studies have provided many lines of evidence that specific homeodomain
      factors act to regulate differentiation into specific neuron types. However,
      these studies have mainly focused on the caudal CNS, while in the forebrain, the
      regulation of neuron specification remains relatively unknown. To investigate the
      genetic regulatory networks that control neuron differentiation in the forebrain,
      we have analyzed the expression patterns and functions of DLX homeodomain factors
      in the ventral thalamus of early mouse embryos. During initial neurogenesis (E9.5
      E10.5), DLX(+) cells are the first progenitors to make terminal divisions and
      differentiate as neurons. We have defined a set of regulatory genes coexpressed
      with DLX, in both progenitors (PAX6 and MASH1) and in the differentiating neurons
      (PAX6, along with a combination of LIM-type homeodomain factors, including ISL1,
      Lhx1/Lim1, and Lhx5/Lim2). These initial neurons express tyrosine hydroxylase
      (TH), and become the PAX6-expressing A13 dopaminergic neurons of the zona
      incerta. To test for DLX function, the initial differentiation of the ventral
      thalamic neurons was examined in embryos mutant for Dlx1 and Dlx2. Dlx1/2 double
      homozygous mutants formed ventral thalamic neurons, but these neurons lacked
      PAX6, ISL1, and TH expression. These data suggest that DLX genes act as forebrain
      specific factors linking general neuron-inducing signals to region-specific
      neuron differentiation programs.

PMID- 12799142
TI  - Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery
      from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice.
AB  - We have studied the consequences of the constitutive acetylcholinesterase (AChE)
      deficiency in knockout mice for the AChE gene on the subcellular localization of
      the m2 receptor (m2R) and the regulation of its intraneuronal
      compartmentalization by the cholinergic environment, using immunohistochemistry
      at light and electron microscopic levels. (1) In AChE +/+ mice in vivo, m2R is
      mainly located at the neuronal membrane in striatum, hippocampus, and cortex. In
      AChE -/- mice, m2R is almost absent at the membrane but is accumulated in the
      endoplasmic reticulum and Golgi complex. (2) In vivo and in vitro (organotypic
      culture) dynamic studies demonstrate that the balance between membrane and
      intracytoplasmic m2R can be regulated by the cholinergic influence: In AChE -/-
      mice, m2R is translocated from the cytoplasm to the cell surface after (1)
      blockade of muscarinic receptors by atropine, (2) supplementation of AChE -/-
      neurons with AChE in vitro, and (3) disruption of the cortical and hippocampal
      cholinergic afferents in vitro. Our results suggest that the neurochemical
      environment may contribute to the control of the abundance and availability of
      cell surface receptors, and consequently to the control of neuronal sensitivity
      to neurotransmitters or drugs, by regulating their delivery from the endoplasmic
      reticulum and Golgi complex.

PMID- 12799143
TI  - Mutational analysis of N-Bak reveals different structural requirements for
      antiapoptotic activity in neurons and proapoptotic activity in nonneuronal cells.
AB  - N-Bak, a neuron-specific BH3-only splice variant of Bak, is proapoptotic when
      overexpressed in nonneuronal cells, but antiapoptotic in NGF-deprived sympathetic
      neurons. We generated mutants of N-Bak and compared their activities in COS-7 or
      Neuro2A cells to those in NGF-deprived sympathetic neurons. A C-terminal deletion
      shortly after the BH3 domain of N-Bak compromised its neuroprotective activity
      but had little effect on its cytotoxic activity in nonneuronal cells. Amino acid
      changes in the BH3 domain of N-Bak differently affected its function in
      nonneuronal cells and in neurons. The same changes in the BH3 domain of longer
      Bak isoform affected its function similarly in nonneuronal cells and neurons. C
      terminally truncated Bax, a structural analogue of N-Bak, was also
      neuroprotective, whereas Blk, a different BH3-only protein was apoptotic in
      neurons. Thus, neuron-specific antiapoptotic interactions require a "N-Bak-type"
      conformation, not just a BH3 domain, whereas the presence of a BH3 domain in the
      Bak protein is sufficient to kill nonneuronal cells.

PMID- 12799145
TI  - Quorum sensing and its relevance to infectious diseases.
AB  - Quorum sensing allows bacteria to detect the density of their own species and
      alter their metabolism to take advantage of this density. Quorum sensing is used
      by a wide variety of bacteria including human pathogens. Quorum sensing genes are
      important for the pathogenic potential of Pseudomonas aeruginosa and
      Staphylococcus aureus, as well as other invasive bacteria. An understanding of
      quorum sensing may lead to new therapeutic strategies.

PMID- 12799144
TI  - Analysis of doppel protein toxicity.
AB  - The recently described doppel protein (Dpl) is a homologue of the prion protein
      (PrP(c)). This protein, expressed in the brains of mice that lack the expression
      of PrP(c), causes neuronal death as the mice age. Previous studies have suggested
      this neuronal damage is caused by oxidative assault and changes in the activity
      of NOS proteins. We investigated the toxicity of Dpl in cell culture models and
      showed that Dpl was toxic to neurons. This toxicity was inhibited by the
      expression of PrP(c) and possibly involved direct interaction between the two
      proteins. The mechanism of toxicity involved stimulation of nitric oxide
      production via activation of the nitric oxide synthases, nNOS and iNOS. This
      mechanism of toxicity is quite different from that of PrP(Sc) and does not
      require the protein to change conformation. These results provide the first
      evidence for the mechanism of Dpl toxicity.

PMID- 12799146
TI  - NRAMP1 polymorphisms, susceptibility and clinical features of tuberculosis.
AB  - OBJECTIVES: To study whether NRAMP1 gene polymorphisms in a Japanese population
      affect susceptibility to tuberculosis and clinical features of tuberculosis.
      METHODS: Polymerase chain reaction and restriction fragment-length polymorphism
      analyses were used to type NRAMP1 polymorphisms in 95 patients with pulmonary
      tuberculosis and 90 controls. Clinical features of patients also were
      investigated. RESULTS: No association was seen between susceptibility to
      tuberculosis and NRAMP1 polymorphisms. Patients with the D543N A allele were
      significantly more likely than others to develop a cavitary lesion; by logistic
      regression analysis with adjustment for gender, age, and presence of diabetes,
      the odds ratio in patients with an A allele was 5.16 (95% confidence interval,
      1.30-20.45). CONCLUSIONS: Genetic variation in the human NRAMP1 gene may be
      associated with cavitation in patients with tuberculosis.

PMID- 12799147
TI  - Osteopenia in HIV-infected women prior to highly active antiretroviral therapy.
AB  - BACKGROUND AND OBJECTIVES: Multiple endocrine and metabolic consequences of human
      immunodeficiency (HIV) infection exist that alter bone metabolism in patients
      with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has
      been associated with antiretroviral therapy particularly with protease
      inhibitors. However, there is very little data on bone metabolism in female
      subjects with AIDS prior to highly active antiretroviral therapy. METHODS: Bone
      mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in
      50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine
      and the Ward's triangle of the left hip. Additional parameter assessed were
      demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical
      markers of bone metabolism. None of the patients received reverse transcriptase
      inhibitors or protease inhibitors, vitamin D or calcium-supplementation. RESULTS:
      The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D)
      were significantly reduced compared to 50 age-matched female healthy controls.
      Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine
      excretion were elevated (P<0.01) and were likewise significantly correlated with
      the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered
      (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was
      found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below
      normal) was diagnosed in 31 (62%). No patient had a fracture since being infected
      with HIV. The BMD was reduced both in lumbar spine and the hip measured in the
      left Ward's triangle. There were significant positive correlation between the CD4
      counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of
      disease correlated with BMD. The reduced bone formation rate was linked to
      progressive loss of CD4-cell count. CONCLUSION: Osteopenia in HIV-infected female
      subjects is commonly manifested both in lumbar spine and Ward's triangle of the
      hip. There is a dissociation between lowered markers of bone formation rate and
      the increased bone resorption expressed as elevated urinary crosslinks and
      calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute
      to a negative calcium balance and inhibition of bone formation. Our results
      suggest that further research is necessary to determine, whether low levels of
      1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D
      is known as an endogenous immune modulator suppressing formation of activated T
      cells and cell proliferation.

PMID- 12799148
TI  - Cytopathogenicity of acanthamoeba, vahlkampfia and hartmannella: quantative &
      qualitative in vitro studies on keratocytes.
AB  - OBJECTIVES: To compare the cytopathogenicity of Vahlkampfia and Hartmannella
      clinical isolates with a type culture of Acanthamoeba castellanii. METHODS: The
      cytopathic effect produced during 24 h co-incubation with cultured keratocytes
      was assessed at set time intervals. Formal quantative studies involved image
      analysis of the area of cells remaining after 6 h. The mechanism of
      cytopathogenicity was elucidated using time-lapse video, light and scanning
      electron microscopy. The ability to produce cell damage in the absence of
      physical contact was studied using the transwell apparatus. The role of apotosis
      was also investigated. RESULTS: All three isolates produced near destruction of
      the keratocyte monolayer within 24 h, although initial cell destruction was more
      rapid with Acanthamoeba. For all three genera, the mechanism of cell damage
      involved physical attack and trogocytosis: cytopathic products were also
      implicated as cell damage was produced in the absence of physical contact, but
      apoptosis was not demonstrated. CONCLUSIONS: While the results do not prove that
      Vahlkampfia and Hartmannella are pathogens, they provide important evidence
      supporting the thesis that they cause keratitis by demonstrating that their
      ability to produce a cytopathic effect on keratocytes in vitro is similar in
      magnitude and mechanism to that of the known pathogen Acanthamoeba castellanii.
      The mechanisms by which small free-living amoebae produce cell damage is poorly
      understood. The ability of genera of amoebae other than Acanthamoeba to produce
      corneal infection remains controversial. In this study, the cytopathogenicity of
      Vahlkampfia and Hartmannella isolated from a case human keratitis are compared
      both quantitatively and qualitatively with that to the known pathogen
      Acanthamoeba castellanii. The results suggest that representatives of each of the
      3 genera produce a similar degree of cytopathic effect on keratocytes after 24h
      of co-incubation and that a combination of physical and chemical factors are
      responsible.

PMID- 12799149
TI  - Cardiac troponin I: a reliable marker and early myocardial involvement with
      meningoencephalitis after fatal enterovirus-71 infection.
AB  - OBJECTIVES: A major outbreak of enterovirus 71 (EV71) in Taiwan in 1998 caused
      many severe cases and 78 deaths. Our purpose was to find reliable markers and
      early indicators of fatal EV71 central nervous system (CNS) infection. METHODS:
      From June 2000 to November 2001, 21 patients with hand foot mouth disease or
      herpangina with CNS infection were admitted to Kaohsiung Veterans General
      Hospital. All 21 had culture-confirmed EV71 infection or were EV71 IgM positive.
      Patients were divided into two groups: group I included the five fatalities at
      our institution and group II, the 16 surviving patients. RESULTS: Of the 21
      infants and children with EV71 infection with CNS involvement, MR imaging studies
      were completed on 17, and 15 showed hyperintensity in the posterior portions of
      brain stem. All patients received intravenous immunoglobulin (IVIG) 1 g/day for
      two days and supportive care. Five patients rapidly deteriorated owing to
      irreversible hypotension and died. The other 16 patients recovered completely
      without sequel. In group I patients, the decrease of cardiac ejection function is
      significant and laboratory findings showed lower platelet count (P=0.0192). The
      mean of initial cTnI level for groups I and II was 10.6+/-11.6 and 0.48+/-0.55
      ng/dl, respectively, higher in group I than in II (P=0.0019). CONCLUSION: We
      hypothesized that like patients with severe burns, those with severe EV-71 CNS
      meningoencephalitis have varying degrees of non-ischemic cardiac injury,
      manifesting as leakage of cTnI from myocytes into the circulation. EV-71 CNS
      meningoencephalitis likely to die with an early myocardial involvement evidenced
      by reduced ejection fraction and release of cTnI. We conclude that fatal EV71 CNS
      infection quickly leads to death due to severe encephalopathy associated with
      cardiomyopathy.

PMID- 12799150
TI  - Bartonella quintana and Mycobacterium tuberculosis coinfection in an HIV-infected
      patient with lymphadenitis.
AB  - Cat scratch disease (CSD) is usually associated with Bartonella henselae
      infection in patients with a history of cat exposure, but Bartonella quintana may
      also be a cause of chronic lympadenopathy in patients with cat or flea contact.
      The lymph node histopathology of CSD and tuberculosis may be indistinguishable.
      We report herein the first description of lymph node coinfection with B. quintana
      and M. tuberculosis in a 32-year HIV-infected woman. Culture of lymph node biopsy
      material on Columbia agar with sheep blood and on human endothelial cells in
      shell vial allowed us to isolate not only B. quintana, but also M. tuberculosis
      hominis.

PMID- 12799151
TI  - Urogenital infection by Mycobacterium bovis relapsing after 50 years.
AB  - A 64-year-old man was referred to chest clinic after presenting initially with
      painless haematuria. Bladder biopsies showed granulomatous inflammation and
      subsequent urine cultures grew Mycobacterium bovis. He had been treated
      empirically for genito-urinary tuberculosis twice previously and on both
      occasions his haematuria ceased. Although the early hospital notes have been
      destroyed we believe this represents a very late and recurrent relapse of
      cystitis due to M. bovis.

PMID- 12799152
TI  - Pneumococcal meningitis in an immunocompetent adult with a cochlear implant.

PMID- 12799153
TI  - Amoebic abscess in the left lobe of the liver masquerading as pyelonephritis.

PMID- 12799154
TI  - A case of epididymo-orchitis and paravertebral abscess due to brucellosis.
AB  - Brucellosis is a zoonotic infection involving many systems and it is widespread
      in Turkey. Involvement of muscular and skeletal systems is a common complication
      of brucellosis. Involvement of genitourinary system (epididymo-orchitis) is a
      rarer complication (Sozen TH. Infeksiyon Hastaliklari. 1996; pp. 486-493; Edward
      J. Young. Principles and Practice of Infectious Diseases, Vol. 2, 5th edn. 2000;
      pp. 22386-22393). Brucellosis accompanied by abscess formation in the vertebra is
      frequently seen in the elderly and patients with a chronic disease (Sozen TH.
      Infeksiyon Hastaliklari. 1996; pp. 486-493; Edward J. Young. Principles and
      Practice of Infectious Diseases, Vol. 2, 5th edn. 2000; pp. 22386-22393; Af-Eissa
      YA, Kambal AM et al. Ann Rheum Dis 1990;49 : 896-900; Colmenore JD, Cisneron JM,
      Orjuela DL et al. Infection 1992; 20: 38-42). Brucellosis accompanied by
      paravertebral abscess and epididymo-orchitis is extremely rare. In this report,
      we present a case of epididymo-orchitis and paravertebral abscess due to
      brucellosis.

PMID- 12799155
TI  - Clostridium perfringens septicemia with thrombophlebitis of the portal vein.
AB  - We report a case of patient with Clostridium perfringens septicemia and
      thrombophlebitis of the portal vein (pylephlebitis), probably secondary to an
      initially unrecognized gastric ulcer. The extension of the thrombosis from the
      superior mesenteric vein to the main portal vein on a repeat CT scan and
      subsequent partial resolution of the thrombus with antibiotic therapy alone,
      suggested that Clostridium perfringens bacteremia may have enhanced the formation
      of thrombus. The coexistence of Clostridium perfringens septicemia and
      pylephlebitis should prompt a search for intra-abdominal processes as the portal
      of entry of infection.

PMID- 12799156
TI  - Encephalopathy induced by oral acyclovir in a patient with normal renal function.

PMID- 12799157
TI  - A model for tool-use traditions in primates: implications for the coevolution of
      culture and cognition.
AB  - Inspired by the demonstration that tool-use variants among wild chimpanzees and
      orangutans qualify as traditions (or cultures), we developed a formal model to
      predict the incidence of these acquired specializations among wild primates and
      to examine the evolution of their underlying abilities. We assumed that the
      acquisition of the skill by an individual in a social unit is crucially
      controlled by three main factors, namely probability of innovation, probability
      of socially biased learning, and the prevailing social conditions (sociability,
      or number of potential experts at close proximity). The model reconfirms the
      restriction of customary tool use in wild primates to the most intelligent
      radiation, great apes; the greater incidence of tool use in more sociable
      populations of orangutans and chimpanzees; and tendencies toward tool manufacture
      among the most sociable monkeys. However, it also indicates that sociable
      gregariousness is far more likely to produce the maintenance of invented skills
      in a population than solitary life, where the mother is the only accessible
      expert. We therefore used the model to explore the evolution of the three key
      parameters. The most likely evolutionary scenario is that where complex skills
      contribute to fitness, sociability and/or the capacity for socially biased
      learning increase, whereas innovative abilities (i.e., intelligence) follow
      indirectly. We suggest that the evolution of high intelligence will often be a
      byproduct of selection on abilities for socially biased learning that are needed
      to acquire important skills, and hence that high intelligence should be most
      common in sociable rather than solitary organisms. Evidence for increased
      sociability during hominin evolution is consistent with this new hypothesis.

PMID- 12799158
TI  - Bias and error in estimates of mean shape in geometric morphometrics.
AB  - Sampling experiments were performed to investigate mean square error and bias in
      estimates of mean shape produced by different geometric morphometric methods. The
      experiments use the isotropic error model, which assumes equal and independent
      variation at each landmark. The case of three landmarks in the plane (i.e.,
      triangles) was emphasized because it could be investigated systematically and the
      results displayed on the printed page. The amount of error in the estimates was
      displayed as RMSE surfaces over the space of all possible configurations of three
      landmarks. Patterns of bias were shown as vector fields over this same space.
      Experiments were also performed using particular combinations of four or more
      landmarks in both two and three dimensions. It was found that the generalized
      Procrustes analysis method produced estimates with the least error and no pattern
      of bias. Averages of Bookstein shape coordinates performed well if the longest
      edge was used as the baseline. The method of moments (Stoyan, 1990, Model.
      Biomet. J. 32, 843) used in EDMA (Lele, 1993, Math. Geol. 25, 573) exhibits
      larger errors. When variation is not small, it also shows a pattern of bias for
      isosceles triangles with one side much shorter than the other two and for
      triangles whose vertices are approximately collinear causing them to resemble
      their own reflections. Similar problems were found for the log-distance method of
      Rao and Suryawanshi (1996, Proc. Nat. Acad. Sci. 95, 4121). These results and
      their implications for the application of different geometric morphometric
      methods are discussed.

PMID- 12799159
TI  - Suspensory locomotion of Lagothrix lagothricha and Ateles belzebuth in Yasuni
      National Park, Ecuador.
AB  - A comparative field study of the locomotion of woolly monkeys (Lagothrix
      lagothricha) and spider monkeys (Ateles belzebuth) in undisturbed rainforest of
      northeastern Ecuador reveals substantial differences in their use of suspensory
      modes. Ateles performed both more brachiation (by forelimbs and tail, with trunk
      rotation), and forelimb swing (similar to brachiation, but without trunk
      rotation) than Lagothrix. In contrast, in Lagothrix 20% of suspensory movement
      was by pronograde forelimb swing, which resembles forelimb swing except that the
      body is held in a pronograde orientation due to the tail and/or feet
      intermittently grasping behind the trailing forelimb. Ateles never exhibited this
      mode. Both brachiation and forelimb swing by Ateles were more dynamic than in
      Lagothrix, consisting of higher proportions of full-stride bouts (versus single
      step). Both species used smaller supports for suspensory than for quadrupedal
      locomotion, and Ateles used both smaller and larger supports for suspension than
      did Lagothrix. Analysis of support inclination shows that both species tended to
      perform more above-support movement on horizontal supports and more below-support
      (suspensory) movement from oblique supports. Our attempt to elucidate the aspects
      of canopy structure that favor suspension suggests the need for additional kinds
      of observational data, focusing on the "immediate structural context" of
      positional events.

PMID- 12799160
TI  - Internal nasal floor configuration in Homo with special reference to the
      evolution of Neandertal facial form.
AB  - The presence of a steeply sloping or depressed nasal floor within the nasal
      cavity of Neandertals is frequently mentioned as a likely specialization or
      autapomorphy. The depressed nasal floor has also been seen as contributing to a
      relatively more capacious nasal cavity in Neandertals, which is tied to cold
      climate respiratory adaptation and energetics. These observations have been
      limited largely to a relatively few intact crania, and the character states
      associated with this trait have not been as precisely codified or analyzed as
      those published for Plio-Pleistocene hominins (McCollum et al., 1993, J. Hum.
      Evol. 24, 87; McCollum, 2000, Am. J. Phys. Anthrop. 112, 275). This study
      examines the internal nasal floor topography in complete crania and isolated
      maxillae in European, west Asian, and African fossil Homo (n=158) including 25
      Neandertals, and a wide range of recent humans from Europe, the Near East, and
      Africa (n=522). The configuration of the internal nasal floor relative to the
      nasal cavity entrance is codified as: 1) level, forming a smooth continuous
      plane; 2) sloped or mildly stepped; or 3) bilevel with a pronounced vertical
      depression. The frequency of these nasal floor configurations, and their
      relationship to both nasal margin cresting patterning and a comprehensive set of
      nasofacial metrics is examined. Neandertals show a high frequency of the bilevel
      (depressed) configuration in both adults and subadults (80%), but this
      configuration is also present in lower frequencies in Middle Pleistocene African,
      Late Pleistocene non-Neandertal (Skhul, Qafzeh), and European Later Upper
      Paleolithic samples (15%-50%). The bilevel configuration is also present in lower
      frequencies (ca. 10%) in all recent human samples, but attains nearly 20% in some
      sub-Saharan African samples. Across extinct and extant Homo (excluding
      Neandertals), internal nasal floor configuration is not associated with piriform
      aperture nasal margin patterning, but the two are strongly linked in Neandertals.
      Variation in internal nasal floor configuration in recent humans is primarily
      associated with internal nasal fossa breadth and nasal bridge elevation, whereas
      in fossil hominins, it is associated primarily with variation in facial height.
      Cold-climate and activity-related thermal adaptation as an explanation for the
      high frequency of pronounced nasal floor depression in Neandertals is
      inconsistent with all available data. Alternatively, variation in internal nasal
      floor configuration is more likely related to stochastically derived populational
      differences in fetal nasofacial growth patterns that do not sharply differentiate
      genus Homo taxa (i.e., cladistically), but do phenetically differentiate groups,
      in particular the Neandertals, especially when considered in combination with
      other nasofacial features.

PMID- 12799161
TI  - The one-million-year-old Homo cranium from Bouri (Ethiopia): a reconsideration of
      its H. erectus affinities.

PMID- 12799162
TI  - Lemudong'o: a new 6 Ma paleontological site near Narok, Kenya Rift Valley.

PMID- 12799163
TI  - Use of the mathematical principle of inversion in young children.
AB  - An important issue in the development of mathematical cognition is the extent to
      which children use and understand fundamental mathematical concepts. We examined
      whether young children successfully use the principle of inversion and, if so,
      whether they do so based on qualitative identity, length, or quantity. Twenty
      four preschool children and 24 children in Grade 1 were presented with three-term
      inversion problems (e.g., 3+2-2) and standard problems of similar magnitude
      (e.g., 2+4-3). Problems were presented in three conditions to determine whether
      children used inversion at all and, if so, whether their decisions were based on
      quantitative or nonquantitative features of the problems. Both preschool and
      Grade 1 children showed evidence of using inversion in a fully quantitative
      manner, indicating that this principle is available in some form prior to
      extensive formal instruction in arithmetic.

PMID- 12799164
TI  - Arithmetic fact mastery in young children: a longitudinal investigation.
AB  - Children with poor arithmetic fact mastery (n=45) at the end of third grade were
      compared to grade-level peers with good arithmetic fact mastery (n=60) in
      competencies related to reading and mathematics. Children were assessed
      longitudinally across second and third grades. When predictor variables such as
      IQ were held constant, the poor fact mastery and good fact mastery groups
      performed at about the same level and progressed at a comparable rate on math
      story problems and on broad reading achievement. The groups also progressed at a
      comparable rate on broad math achievement, although children with poor fact
      mastery performed at a significantly lower level. Children with poor fact mastery
      showed remarkably little growth on timed number facts during the study period,
      despite normal growth in other areas of mathematics. Deficits in fact mastery are
      highly persistent and appear to be independent of reading and language abilities.

PMID- 12799165
TI  - How do children coordinate simultaneous upper and lower extremity tasks? The
      development of dual motor task coordination.
AB  - When performing simultaneous clapping with walking or galloping, adults adopt
      coupled, consistent and stable dual motor task coordination; do developmental
      trends in this coordination exist? In this study, we measured and compared
      coupling characteristics, consistency across trials and variability of phasing in
      4-, 6-, 8-, and 10-year-olds (n=44) as they also performed the same dual motor
      task. For walk/clap, children adopted specific coupling patterns like adults by 8
      years and with the same consistency by 10 years. Across age, children became less
      variable in clap and step movements separately and as coupled together. In the
      gallop/clap, children did not resemble adults in coupling patterns by 10 years
      but all measures were becoming more consistent across age. We discuss dual motor
      task coordination as a function of age and task complexity using a "dynamic"
      perspective within a developmental context.

PMID- 12799166
TI  - What response times tell of children's behavior on the balance scale task.
AB  - Analysis of accuracy of responses to balance scale problems gives a global idea
      of the cognitive processes that underlie problem-solving behavior on this task.
      We show that response times (RTs) provide additional detailed information about
      the kind and duration of these processes. We derive predictions about the RTs
      from Siegler's (1981) model for the balance scale task, including the
      counterintuitive prediction that young adults are slower than children in solving
      particular balance scale problems. The predictions were tested in a study in
      which 191 6- to 22-year-old participants were presented with a computerized
      balance scale task. RTs were analyzed with regression models. In addition to
      qualitative differences between items, we also modeled quantitative differences
      between items in the regression models. Analyses supported the predictions and
      provided additional knowledge on the rules. Rule II was reformulated as a rule
      that always involves the encoding, but not always the correct application of the
      distance cue. RTs provided evidence for the use of a buggy-rule and not an
      addition-rule. Finally, a relation between rule inconsistency and increased RT
      was found.

PMID- 12799167
TI  - The developmental course of processing speed in children with and without
      learning disabilities.
AB  - This study contrasted the development of processing speed in children with and
      without learning disabilities. We examined whether the same global mechanism
      presumed to be responsible for the normal developmental improvement in processing
      speed might also be associated with the processing speed deficiencies observed in
      children with learning impairments. One hundred and twenty-two children with
      learning disabilities in reading and/or math and 206 non-disabled community
      controls participated. There were no differences in relation of age to the
      development of processing speed for children with and without learning
      disabilities. We interpreted these results as suggesting that the underlying
      etiologies for the normal developmental change in processing speed and for the
      relative deficiencies in processing speed seen among children with learning
      disabilities were different.

PMID- 12799168
TI  - Differential effects of testosterone and progesterone on the activation and
      retention of courtship behavior in sexual and parthenogenetic whiptail lizards.
AB  - Both testosterone (T) and progesterone (P) facilitate the expression of male
      typical sexual behavior in a variety of animals, including rodents and lizards.
      In two species of whiptail lizards, Cnemidophorus inornatus and C. uniparens,
      both hormones elicit the full repertoire of courtship behavior. However, the
      relative efficacy of the two hormones is unknown. In Experiments 1 and 2 we
      assessed differences in capacity of exogenous T and P to induce male-typical
      courtship behavior in gonadectomized whiptail lizards. In both species,
      individuals implanted with T showed more frequent courtship behavior relative to
      those implanted with P or cholesterol. In Experiments 3 and 4 we examined whether
      T and P differentially affected the retention of courtship behavior following
      implant removal. In both species, individuals implanted with T showed more
      courtship behavior following implant removal than those previously given P. In
      these experiments, implants were removed at a time when individuals in both
      groups were behaviorally similar; therefore, the differences in behavior
      following implant removal were not due to differences in the amount of courtship
      experience. Taken together, the hormone that was more effective at activating
      courtship behavior was also more effective at maintaining courtship behavior
      following implant removal. In summary, though both T and P can elicit identical
      sexual behaviors in both whiptail species, T has a greater and more lasting
      effect on courtship behavior and possibly on the neural circuits underlying
      courtship behavior.

PMID- 12799169
TI  - Fetal testosterone surge: specific modulations induced in male rats by maternal
      stress and/or alcohol consumption.
AB  - Plasma testosterone (T) was measured in control male and female rats on
      gestational days 16, 17, 18, 19, and 20 and on days 17-20 in males from dams who
      were fed ethanol and/or were stressed during pregnancy. Circulating T in control
      males showed an earlier rise, yielding a longer period of prenatal T elevation,
      than was reported previously (Endocrinology 106 (1980)306). Compared to control
      males, exposure to alcohol-alone augmented T on days 18 and 19, stress-alone
      attenuated prenatal T, and the combination of stress and alcohol completely
      blocked the normal rise in T between days 17 and 18. When these prenatal
      alterations in T are viewed along with effects these same treatments have on the
      postparturient T surge (Horm. Behav. 41 (2002) 229), a possible explanatory
      mechanism emerges for the uniquely different behavioral patterns of sexual
      behavior differentiation induced in males by prenatal exposure to alcohol,
      stress, or both factors. Whereas the potential for feminine behavior is retained
      to the extent that either the prenatal or the neonatal T surge is attenuated, the
      male potential is more sensitive to reductions in the fetal surge and is
      maximally disrupted if both the prenatal and the postparturitional T surges are
      suppressed.

PMID- 12799170
TI  - Fecal corticosteroids in a territorial bird selected for different personalities:
      daily rhythm and the response to social stress.
AB  - In this study we tested the hypothesis that in a passerine bird (great tit, Parus
      major) individuals differing for coping strategies differ in the magnitude of the
      adrenocortical response to social stress as well. Furthermore, we aimed at
      characterizing daily rhythms in corticosteroid release before and after social
      stress. We used 16 males from either of two lines bidirectionally selected for
      different coping strategies (fast and slow explorers). Social stress was induced
      by confrontation with an aggressive resident male. Corticosteroid metabolites
      were analyzed in feces collected at 90-min intervals from 900 to 1630 h on a
      baseline day, on the day of the social conflict, and on the following day. In
      both days and in both lines levels varied with time of day in a robust rhythm
      with a peak in the first sample of the morning and a trough at the end of the
      light phase. This rhythm correlates with activity (perch hopping). An overall
      increase in levels relative to baseline day was observed between 30 and 140 min
      after the challenge. Birds of the less aggressive and more cautious line (slow
      explorers) showed a trend for a higher response compared to birds of the more
      aggressive and bolder line (fast explorers), which showed almost no response. On
      the day after the challenge the birds of the slow line exhibited significantly
      reduced corticosteroid secretion, probably due to an increased negative feedback.
      The results provide evidence for a physiological basis of different coping
      strategies in birds, emerging in response to social stress and with a pattern
      similar to that in other vertebrates.

PMID- 12799171
TI  - Hormonal regulation of agonistic and affiliative behavior in female mongolian
      gerbils (Meriones unguiculatus).
AB  - Ovarian steroids and oxytocin (OT) have been implicated in the regulation of
      social behaviors. The purpose of the present study was to examine hormonal
      substrates of aggression and affiliation in the female Mongolian gerbil (Meriones
      unguiculatus), a highly social, monogamous rodent. Sexually naive adult females
      were paired with sexually experienced males for 48 h and their interactions
      videotaped. Females were gonadally intact and tested during vaginal estrus (INT)
      or ovariectomized and observed after the following treatments, administered by
      means of sc injections: EBEB (7 days of estradiol-benzoate); EBP (2 days of EB
      followed by progesterone), SALEB (saline, days 1-5 then 2 days of EB), OTEB (OT
      for days 1-5 then 2 days of EB); OTOIL (OT for days 1-5 then 2 days of OIL); or
      SALOIL (saline days 1-5 then 2 days of OIL). During the first hour of pairing INT
      females displayed higher levels of affiliation and lower levels of sniffing and
      agonistic behavior than SALOIL females. All hormonal treatments reduced agonistic
      behaviors when compared to SALOIL, although none of the hormonal treatments
      restored affiliation to INT levels. During the 48-h test overt aggression varied
      by treatment with INT, EBEB, EBP, and OTEB females displaying lower levels than
      SALOIL, while all groups displayed similar levels of affiliation. The results
      indicate that OT and E play a significant role in regulating male-directed
      aggressive behavior in females and that the presence of ovarian hormones as well
      as OT can increase affiliation during initial contact. Over a sustained period of
      cohabitation social cues appear to be more important in regulating affiliation
      than gonadal hormones.

PMID- 12799172
TI  - Testosterone is correlated with courtship but not aggression in the tropical buff
      banded rail, Gallirallus philippensis.
AB  - Past studies into the roles of testosterone in birds have focused on species that
      occur in temperate regions. In such species, plasma testosterone levels are high
      during the establishment of territories in the spring and are associated with
      increased aggression. In contrast to most temperate species, tropical birds
      frequently defend territories year-round, during which time territoriality often
      occurs in a nonsexual context. The few studies that have been carried out on
      tropical birds show lower levels of circulating testosterone than occur in their
      temperate counterparts. In some year-round territorial tropical species,
      testosterone and aggression are dissociated, while in other species testosterone
      still plays a role in regulating aggression. This study examined the relationship
      between aggression and plasma testosterone levels in a year-round territorial,
      subtropical population of the buff-banded rail with characteristics typical of
      tropical species. Peak testosterone levels were substantially lower than those
      found in temperate species. Males displayed a seasonal peak in plasma
      testosterone level when their partners were most likely to be fertile. At other
      times, testosterone levels were mostly undetectable, despite year-round
      territoriality. We found that T levels increased with courtship behavior but
      showed no relationship with aggression, supporting the hypothesis that
      dissociation between testosterone and territoriality may be widespread among
      tropical avian taxa.

PMID- 12799173
TI  - Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by
      maternal separation.
AB  - This study investigated the effects of maternal separation in C57BL/6 male and
      female mice during infancy on later adult fear and anxiety behaviors.
      Additionally, we observed the maternal behavior of the dams to examine aspects of
      maternal care that may be modulated by daily bouts of separation. In males, mice
      that experienced maternal separation during the neonatal period displayed
      significantly higher levels of anxiety and fear behavior, as measured by the open
      field test and elevated plus maze, compared to control, standard facility reared
      males. In females, however, maternal separation reduced anxiety and fear behavior
      in the open field test, but only when the females were in the diestrous phase of
      their estrous cycle. The 30-min daily observation of the dams revealed that the
      separation did not significantly alter the frequency of the maternal care
      provided by the dam at the time point measured. These results indicate that the
      emotionality of adult male and female mice can be modulated by maternal
      separation. However, this effect is dependent on the sex of the offspring and the
      phase of the estrous cycle of the female.

PMID- 12799174
TI  - Fear and stress reactions in two species of duck and their hybrid.
AB  - Susceptibility to fear and stress has often been studied in birds using selection
      experiments. Crosses between different species of the same genus have also been
      used to study the type of transmission observed for "fixed action patterns." In
      this experiment we used a cross between two species (male muscovy and female
      pekin ducks) to study the genetic transmission of various characteristics of fear
      reactions and adrenal activity. Males of the three genetic types (two parental
      species and the hybrid) were submitted to tonic immobility and fear of man tests.
      Blood was collected for corticosterone assay before and after physiological
      stress or injection of 5 microg/kg of immediate synacthen (ACTH agonist). The
      muscovy duck showed lower levels of fear reactions than the pekin duck in the
      majority of behavioral tests (six of eight). Corticosterone levels were also
      nearly always the lowest in muscovy ducks (five of six). Generally speaking, the
      muscovy duck appeared to be less fearful and less susceptible to stress than the
      pekin duck. The mule duck was similar to one parent, midway between the two, or
      showed heterosis for fear of man at 10 weeks of age (more fearful than the two
      parents). Corticosterone levels were midway between the two parents in the mule
      duck with only one exception, i.e., where the pekin duck was dominant. The
      existence of heterosis for fear is surprising, as this character is classically
      considered to be submitted to stabilizing selection. The transmission of
      corticosterone levels and other fear characteristics is, however, compatible with
      stabilizing selection. The results are discussed in terms of adaptability.

PMID- 12799175
TI  - Sex differences in interest in infants in juvenile rhesus monkeys: relationship
      to prenatal androgen.
AB  - Yearling rhesus monkey females interact more with infants than do males. However,
      the continuity of this sex difference throughout the juvenile period is unknown.
      Human females display similar sexually differentiated interest in infants, and
      studies of girls with congenital adrenal hyperplasia suggest that this sex
      difference may be modulated by prenatal androgen exposure. We investigated infant
      interest in 1- to 3-year-old juvenile rhesus monkeys. Hormonal influences on this
      behavior were investigated by treating pregnant females with an androgen-receptor
      blocker (flutamide), testosterone enanthate, or vehicle, early or late in
      gestation. Subjects were reared in their well-established natal groups, composed
      of species-typical matrilineal social structures, including members of all ages.
      Yearling control females interacted with infants more than did yearling control
      males. At 2 and 3 years of age, the magnitude of the sex difference in
      interactions with infants increased markedly, producing effect sizes of more than
      2.5 standard deviations. These effects are larger than those reported in humans.
      Androgen treatment did not affect male or female interactions with infants, but
      late gestation flutamide masculinized aspects of females' interest in infants.
      Although early flutamide prevented complete masculinization of male genitalia,
      this treatment was not accompanied by any alterations in the masculine pattern of
      infant interest. We found no evidence that the robust juvenile sex difference in
      frequency of infant interactions results from socialization. However, it was
      largely unaffected by our hormone manipulations. Whether this reflects
      characteristics of our specific treatments or is evidence of nonhormonal
      influences on infant interest remains unanswered.

PMID- 12799176
TI  - APP intracellular domain formation and unaltered signaling in the presence of
      familial Alzheimer's disease mutations.
AB  - One of the cardinal neuropathological findings in brains from Alzheimer's disease
      (AD) patients is the occurrence of amyloid beta-peptide (Abeta) deposits. The
      gamma-secretase-mediated intramembrane proteolysis event generating Abeta also
      results in the release of the APP intracellular domain (AICD), which may mediate
      nuclear signaling. It was recently shown that AICD starts at a position distal to
      the site predicted from gamma-secretase cleavage within the membrane. This novel
      site, the epsilon site, is located close to the inner leaflet of the membrane
      bilayer. The relationship between proteolysis at the gamma and epsilon sites has
      not been fully characterized. Here we studied AICD signaling in intact cells
      using a chimeric C99 molecule and a luciferase reporter system. We show that the
      release of AICD from the membrane takes place in a compartment downstream of the
      endoplasmic reticulum, is dependent on presenilin proteins, and can be inhibited
      by treatment with established gamma-secretase inhibitors. Moreover, we find that
      AICD signaling remains unaltered from C99 derivatives containing mutations
      associated with increased Abeta42 production and familial AD. These findings
      indicate that there are very similar routes for Abeta and AICD formation but that
      FAD-linked mutations in APP primarily affect gamma-secretase-mediated Abeta42
      formation, and not AICD signaling.

PMID- 12799177
TI  - Generation and maintenance of synchrony in Saccharomyces cerevisiae continuous
      culture.
AB  - Cultures of Saccharomyces cerevisiae grown continuously produce an autonomous
      oscillation in many metabolic outputs. The most conveniently measured variable,
      i.e., dissolved oxygen concentration, oscillates with a period of 40-55 min.
      Previously we have identified two compounds capable of resetting phase,
      acetaldehyde and hydrogen sulfide. The phase-response curves constructed for
      acetaldehyde show a strong (Type 0) response at 3.0 mM and a weak (Type 1)
      response at 1.0 mM. Ammonium sulfide phase-response curves (pulse injected at 1.0
      microM and 3.0 microM) revealed that sulfide is only an effective perturbation
      agent when endogenous sulfide concentrations are at a maximum. Also only Type 1
      phase responses were observed. When the phase-response curve for sulfite (at 3.0
      M) was constructed, phase responses were at a maximum at 60 degrees, indicating
      the possible involvement of sulfite in cell synchronization. It is concluded that
      endogenously produced acetaldehyde and sulfite tune the oscillation of
      mitochondrial energization state whereas sulfide mediates population synchrony.

PMID- 12799178
TI  - Microenvironment and phenotypic stability specify tissue formation by human
      articular cartilage-derived cells in vivo.
AB  - During in vitro expansion, adult human articular cartilage-derived cells (HACDC)
      lose their phenotypic stability and capacity to form cartilage in vivo after 4-6
      population doublings (PD). Nevertheless, HACDC can be efficiently expanded for up
      to 20 PD. Here we show that HACDC can generate cartilage, fibrous tissue,
      skeletal muscle, bone, and adipocytes depending on the balance between phenotypic
      stability and environmental cues. When 5 x 10(6) cells were injected
      intramuscularly into nude mice, early-passage (EP)-HACDC formed cartilage; late
      passage (LP)-HACDC formed mostly fibrous tissue, but a limited number of cells
      contributed to muscle formation. When 0.5 x 10(6) cells were injected into
      regenerating mouse muscle, both EP- and LP-HACDC integrated with host myofibers
      and expressed muscle genes, but a number of EP-HACDC maintained collagen type II
      expression. HACDC seeded into Collagraft and implanted subcutaneously into nude
      mice formed scattered bone islands displaying immunoreactivity for human
      osteocalcin, and expressing human bone-specific genes. Importantly, neither
      collagen type II transcript nor cartilage tissue was detected at 8 weeks after
      implantation. Myogenic, osteogenic, and adipogenic differentiation was induced in
      vitro using specific culture conditions. These findings provide evidence that in
      vivo tissue formation by HACDC is specified by a balance between environmental
      cues and the inherent phenotypic stability.

PMID- 12799179
TI  - Recruitment of human umbilical vein endothelial cells and human primary
      fibroblasts into experimental tumors growing in SCID mice.
AB  - Generation of a vascular network is a hallmark of solid tumor growth, and
      attempts to switch off the tumor angiogenic phenotype are promising. However,
      this angiogenic potential might also be exploited to obtain incorporation into
      tumor vessels of genetically modified third-party cells, which could behave as
      targets of immunologic or pharmacologic attack. With this in mind, we addressed
      the efficiency and selectivity of third-party cell recruitment into experimental
      tumors generated in severe combined immunodeficiency mice. The animals were
      inoculated intraperitoneally with human ovarian carcinoma cell lines and with
      beta-galactosidase (beta-gal)-transduced human umbilical vein endothelial cell
      (HUVEC) or human fibroblasts. Transgenic HUVEC were scattered in tumors, but not
      in normal mouse tissues; immunohistochemical analysis revealed their selective
      homing to tumor vascular structures, over 50% of which contained beta-gal(+)
      cells. Injection of beta-gal-transduced human fibroblasts was also associated
      with transgenic cell incorporation into tumor masses; however, beta-gal(+)
      fibroblasts did not home to tumor blood vessels and were only localized within
      the tumor stroma. These findings show that the recruitment of primary third-party
      cells into the different compartments of experimentally induced tumors is an
      efficient and selective phenomenon and indicate possible alternative ways of
      confronting the tumor angiogenic potential in cancer therapy.

PMID- 12799180
TI  - Identification of sequence determinants of human nuclear dUTPase isoform
      localization.
AB  - dUTP nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and
      pyrophosphate and is the central regulator of cellular dUTP pools. Nuclear (DUT
      N) and mitochondrial (DUT-M) isoforms of the protein have been identified in
      humans and arise from the same gene by the alternative use of 5' exons. Recently,
      it has been shown that these isoforms are aberrantly expressed in some cancers
      and overexpression of dUTPase in the nucleus is associated with resistance to
      chemotherapeutic agents that target thymidylate biosynthesis. In this study, we
      have examined the signals necessary for dUTPase isoform localization using green
      fluorescent protein fusion constructs. We report that the N-terminal 23 amino
      acids of DUT-N are required but not sufficient for complete nuclear localization.
      Within this region, we identified a small cluster of basic residues
      (K(14)R(15)R(17)) that resemble a classic monopartite nuclear localization signal
      (NLS). Mutation of these residues completely abolishes nuclear localization. In
      addition, phosphorylation of Ser11 near the putative NLS has no affect on DUT-N
      nuclear localization. Through deletion analysis we show improved sorting of DUT-N
      to the nucleus when most of the protein sequence is present. Therefore, we
      conclude that DUT-N may contain a complex NLS that is located throughout the
      entire protein.

PMID- 12799181
TI  - Directional motility induced by epidermal growth factor requires Cdc42.
AB  - Cell motility is actuated by a host of intracellular signaling cascades that
      result in movement of the cell in one direction, even without an external
      gradient. Phospholipase C-gamma (PLCgamma) has been shown to be important for
      growth factor-induced lamellipodial protrusion at the front of the cell while
      Cdc42 has been implicated in both filopodium formation at the leading edge and
      control of polarity of migrating cells. We asked whether these asymmetries in
      effector molecules may be linked. When we overexpressed either constitutively
      active, dominant negative, or GFP-tagged Cdc42, wild-type NR6 fibroblasts lost
      directionality, as expected. On epidermal growth factor (EGF) exposure these
      cells produced multiple, transient protrusions in every direction; these
      extensions failed to result in productive motility. GFP-tagged Cdc42 appeared
      transiently at edges of newly formed protrusions in EGF-stimulated cells while
      they moved haphazardly. While PLCgamma is distributed throughout the cell, the
      ratio of active, tyrosyl-phosphorylated PLCgamma was increased at the leading
      edge, where phosphatidylinositol (4,5)-bisphosphate (PIP(2)) hydrolysis is
      concentrated. This co-localization of activities may be due to Cdc42 directing
      PLCgamma to the cell front, as PLCgamma associated with Cdc42 in an EGF-dependent
      manner. We conclude that Cdc42 controls cell polarity, likely in part, through
      its binding to active PLCgamma.

PMID- 12799182
TI  - RA175, which is the mouse ortholog of TSLC1, a tumor suppressor gene in human
      lung cancer, is a cell adhesion molecule.
AB  - RA175, a new immunoglobulin superfamily member, is preferentially expressed
      during differentiation of P19 embryonic carcinoma (EC) cells induced by retinoic
      acid. In the present study, we isolated mouse RA175 cDNA in its entirety and
      showed that RA175 is the mouse ortholog of TSLC1, a tumor suppressor gene in
      human lung cancer. RA175/TSLC1 was localized in the adherent region of human lung
      squamous carcinoma cells and in the differentiated P19 EC cells. RA175/TSLC1
      showed homophilic trans-interaction activity in a Ca(2+)-independent manner.
      RA175/TSLC1 was preferentially expressed in the polarized cells lining the lumen
      of developing mouse lung epithelium. This suggests that RA175/TSLC1 is a cell
      adhesion molecule that is acting as a tumor suppressor gene in the metastasis of
      lung tumors. RA175/TSLC1 may be necessary for cells to remain tightly associated
      in the epithelium, thereby suppressing metastasis.

PMID- 12799183
TI  - Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells.
AB  - Obligate intracellular bacterial pathogens of the genus Chlamydia are reported to
      enter host cells by both clathrin-dependent and clathrin-independent processes.
      C. trachomatis serovar K recently was shown to enter cells via caveolae-like
      lipid raft domains. We asked here how widespread raft-mediated entry might be
      among the Chlamydia. We show that C. pneumoniae, an important cause of
      respiratory infections in humans that additionally is associated with
      cardiovascular disease, and C. psittaci, an important pathogen in domestic
      mammals and birds that also infects humans, each enter host cells via cholesterol
      rich lipid raft microdomains. Further, we show that C. trachomatis serovars E and
      F also use these domains to enter host cells. The involvement of these membrane
      domains in the entry of these organisms was indicated by the sensitivity of their
      entry to the raft-disrupting agents Nystatin and filipin, and by their
      intracellular association with caveolin-1, a 22-kDa protein associated with the
      formation of caveolae in rafts. In contrast, caveolin-marked lipid raft domains
      do not mediate entry of C. trachomatis serovars A, 36B, and C, nor of LGV serovar
      L2 and MoPn. Finally, we show that entry of each of these chlamydial strains is
      independent of cellular expression of caveolin-1. Thus, entry via the Nystatin
      and filipin-sensitive pathway is dependent on lipid rafts containing cholesterol,
      rather than invaginated caveolae per se.

PMID- 12799184
TI  - gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells.
AB  - gp38k (CHI3L1) is a secreted heparin-binding glycoprotein whose expression, in
      vitro, is associated with vascular smooth muscle cell (VSMC) migration and
      invasion into the underlying gelatinous matrix. gp38k is expressed at high levels
      in postconfluent "nodular" VSMC cultures and at low levels in subconfluent
      proliferating cultures. In vivo, expression of gp38k homologs is high in regions
      of tissue remodeling and now has been detected in atherosclerotic plaques and in
      the developing heart. We tested the hypothesis that gp38k functions to modulate
      VSMC adhesion and migration. By use of modified Boyden chambers, gp38k at a
      concentration as low as 1 ng/ml has profound effects on VSMC migration but little
      or no effect on fibroblast migration. In addition, gp38k adsorbed to polystyrene
      surfaces directly promotes VSMC attachment and spreading. Attachment is inhibited
      in the presence of affinity-purified anti-gp38k or 10 mM EDTA. These results
      establish that gp38k is a new vascular cell adhesion and migration factor that
      may have a role in processes leading to vascular occlusion and heart development.
      gp38k may interact with VSMC via an EDTA-sensitive mechanism consistent with
      integrin mediated cell-matrix interaction.

PMID- 12799185
TI  - Glial and neuronal regulation of the lipid carrier R-FABP.
AB  - Neuroembryogenesis critically depends on signaling molecules that modulate cell
      proliferation, differentiation, and the formation of neural networks. In an
      attempt to identify potential morphogenetic active components that are
      distributed in a graded fashion in the developing nervous system, we generated
      substraction libraries of the embryonic nasal and temporal chick retina. Selected
      clones were analyzed by sequencing, Northern and Western blotting, in situ
      hybridization, and immunocytochemistry. Retinal fatty acid-binding protein (R
      FABP) mRNA displayed the most pronounced topographic gradient. R-FABP was most
      strongly expressed in nasal retina, though topographic differences were not
      evident on the protein level. R-FABP expression was subject to a pronounced
      spatio-temporal regulation. Peak expression was at the period of cell
      generation/migration and differentiation. To identify the cell types involved in
      R-FAPB synthesis, ganglion cells as the only retinal projection neurons were
      enriched by enzymatic delayering. Cell somata, axons, and growth cones were R
      FABP immunoreactive. Most interestingly, R-FABP immunoreactivity was critically
      dependent on the growth substratum. It was abrogated when axons grew on isolated
      glial endfeet. Radial glia purified by complement-mediated cytolysis also
      expressed R-FABP at moderate levels. The expression level was significantly
      increased during mitosis and dropped down again in postmitotic cells. Further on,
      transient loss of cell-cell and substratum contact induced a subcellular
      redistribution of R-FABP. In conjunction with the morphogen-binding activity of
      other FABP family members and their impact on cell migration and tissue
      differentiation, R-FABP characteristics suggest a regulatory function during
      retinal histogenesis but not during topographic map formation.

PMID- 12799186
TI  - Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2.
AB  - Bone marrow stromal cells, obtained from postnatal bone marrow, contain
      progenitors able to differentiate into several mesenchymal lineages. Their use in
      gene and cell therapy requires their in vitro expansion and calls for the
      investigation of the culture conditions required to preserve these cells as a
      stem compartment with high differentiative potential during their life span. Here
      we report that fibroblast growth factor 2 (FGF-2)-supplemented bone marrow
      stromal cell primary cultures display an early increase in telomere size followed
      by a gradual decrease, whereas in control cultures telomere length steadily
      decreases with increasing population doublings. Together with clonogenic culture
      conditions, FGF-2 supplementation prolongs the life span of bone marrow stromal
      cells to more than 70 doublings and maintains their differentiation potential
      until 50 doublings. These results suggest that FGF-2 in vitro selects for the
      survival of a particular subset of cells enriched in pluripotent mesenchymal
      precursors and is useful in obtaining a large number of cells with preserved
      differentiation potential for mesenchymal tissue repair.

PMID- 12799187
TI  - Rho protein-mediated changes in the structure of the actin cytoskeleton regulate
      human inducible NO synthase gene expression.
AB  - Rho proteins (Rho, Rac, Cdc 42) are known to control the organization of the
      actin cytoskeleton as well as gene expression. Inhibition of Rho proteins by
      Clostridium difficile toxin B disrupted the F-actin cytoskeleton and enhanced
      cytokine-induced inducible nitric oxide synthase (iNOS) expression in human
      epithelial cells. Also specific inhibition by Y-27632 of p160ROCK, which mediates
      Rho effects on actin fibers, caused a disruption of the actin cytoskeleton and a
      superinduction of cytokine-induced iNOS expression. Accordingly, direct
      disruption of the actin cytoskeleton by cytochalasin D, latrunculin B, or
      jasplakinolide enhanced cytokine-induced iNOS expression. The transcription
      factor serum response factor (SRF) has been described as mediating actin
      cytoskeleton-dependent regulation of gene expression. Direct targets of SRF are
      activating protein 1 (AP1)-dependent genes. All compounds used inhibited SRF- and
      AP1-dependent reporter gene expression in DLD-1 cells. However, the enhancing
      effect of the actin cytoskeleton-disrupting compounds on human iNOS promoter
      activity was much less pronounced than the effect on iNOS mRNA expression.
      Therefore, besides transcriptional mechanisms, posttranscriptional effects seem
      to be involved in the regulation of iNOS expression by the above compounds. In
      conclusion, our data suggest that Rho protein-mediated changes of the actin
      cytoskeleton negatively modulate the expression of human iNOS.

PMID- 12799188
TI  - New cell attachment peptide sequences from conserved epitopes in the carboxy
      termini of fibrinogen.
AB  - Fibrinogen seems to contribute significantly to cell binding and recruitment into
      wounds besides its major role in clot formation. We describe 19- to 21-mer cell
      binding (haptotactic) peptides from the C-termini of fibrinogen beta-chain
      (Cbeta), the extended alphaE chain, and near the C-terminal of the gamma-chain.
      When these peptides were covalently bound to a biologically inert matrix such as
      Sepharose beads (SB), they elicited beads attachment to cells, mostly of
      mesenchymal origin (including fibroblasts, endothelial cells, and smooth muscle
      cells) as well as some transformed cell lines. Based on such haptotactic
      activity, these peptides were termed "haptides." By contrast, peptides homologous
      to fibrinogen C-termini alpha- and gamma-chains elicited no such activity. The
      haptide Cbeta could not block the interaction of fibroblasts with antibodies
      directed against integrins beta(1), alpha(v), alpha(v)beta(1), alpha(v)beta(3),
      and alphaIIbeta(3). Moreover, GRGDS peptide could not inhibit enhanced cell
      binding to SB-Cbeta, as expected from an integrin-mediated process. In soluble
      form the haptides were accumulated in cells with nonsaturable kinetics without
      any toxic or proproliferative effects in concentrations up to 80 microM. These
      findings suggest that the conserved haptidic sequences within fibrin(ogen) can be
      associated with the adhesion and migration of cells into fibrin clots and may
      have a significant role in normal wound healing and in various pathological
      conditions.

PMID- 12799189
TI  - Ilimaquinone inhibits gap-junctional communication prior to Golgi fragmentation
      and block in protein transport.
AB  - Brefeldin A and ilimaquinone are compounds known to affect Golgi structure and
      function. In particular, the transport of proteins is blocked either at the level
      of exit from endoplasmic reticulum (brefeldin) or at cis-Golgi (ilimaquinone).
      Brefeldin caused a slow decrease in gap-junctional communication and a slow loss
      of all phosphorylated forms of connexin43 in hamster and rat fibroblasts, while
      ilimaquinone caused an abrupt decrease in gap-junctional communication and rapid
      loss of only the slowest migrating phosphorylated connexin43 band (P2).
      Ilimaquinone caused these effects prior to any significant Golgi fragmentation,
      especially in hamster fibroblasts. Concurrently, ilimaquinone minimally affected
      protein secretion, while brefeldin caused an instantaneous decrease. These
      results show that ilimaquinone inhibits gap-junctional communication in
      connexin43-expressing cells by a mechanism not dependent on Golgi fragmentation
      or block in protein transport.

PMID- 12799190
TI  - Diacylglycerol kinase-theta is localized in the speckle domains of the nucleus.
AB  - It is well established that the nucleus is endowed with enzymes that are involved
      in lipid-dependent signal transduction pathways. Diacylglycerol (DAG) is a
      fundamental lipid second messenger that is produced in the nucleus. Previous
      reports have shown that the nucleus contains diacylglycerol kinases (DGKs), i.e.,
      the enzymes that, by converting DAG into phosphatidic acid (PA), terminate DAG
      dependent events. Here, we show, by immunofluorescence staining and confocal
      analysis, that DGK-theta localizes mainly to the nucleus of various cell lines,
      such as MDA-MB-453, MCF-7, PC12, and HeLa. Nuclear DGK-theta co-localizes with
      phosphatidylinositol 4,5-bisphosphate (PIP(2)) in domains that correspond to
      nuclear speckles, as revealed by the use of an antibody to the splicing factor SC
      35, a well-established marker for these structures. The spatial distribution of
      nuclear DGK-theta was dynamic in that it was affected by inhibition of mRNA
      transcription with alpha-amanitin. Immuno-electron microscopy analysis
      demonstrated that DGK-theta, PIP(2), and phosphoinositide-specific phospholipase
      Cbeta1 (PLCbeta1) associated with electron-dense particles within the nucleus
      that correspond to interchromatin granule clusters. Cell fractionation
      experiments performed in MDA-MB-453, HeLa, and PC12 cells showed a preferential
      association of DGK-theta with the nucleus. Western blots demonstrated that DGK
      theta was enriched in the nuclear matrix fraction prepared from MDA-MB-453 cells.
      Immunoprecipitation experiments with an antibody to PLCbeta1 revealed in MDA-MB
      453 cells an association between this enzyme and both DGK-theta and
      phosphatidylinositol phosphate kinase Ialpha (PIPKIalpha). Our findings
      strengthen the contention that speckles represent a crucial site for the nuclear
      based inositol lipid cycle. We may speculate that nuclear speckle-located DGK
      theta, on cell stimulation with an agonist, converts to PA the DAG derived from
      PLCbeta1-dependent PIP(2) hydrolysis.

PMID- 12799191
TI  - WT1 expression does not disrupt myogenic differentiation in C2C12 murine
      myoblasts or in human rhabdomyosarcoma.
AB  - WT1 encodes a tissue-specific transcription factor important in early mesenchymal
      differentiation. Altered expression or mutation of WT1 occurs in malignancies
      derived from such tissues. These include Wilms tumour, a paediatric kidney cancer
      that may show heterologous differentiation into primitive skeletal muscle,
      especially in tumours with WT1 mutation. A putative role for WT1 in inhibiting
      myogenesis has been suggested by transient transfection of C(2)C(12) myoblasts.
      However, using a more robust model of stable transfectants of C(2)C(12)
      expressing inducible WT1 isoforms, we found no inhibition of myogenic
      differentiation. We also investigated a possible role for WT1 in the disrupted
      myogenesis seen in rhabdomyosarcoma, a paediatric cancer resembling foetal
      skeletal muscle. WT1 expression levels measured by quantitative real-time reverse
      transcription polymerase chain reaction were low or absent in those tumours with
      a PAX-FKHR fusion gene characteristic of the alveolar subtype, and were higher in
      cases lacking these fusion genes. Overall, there was a weak positive correlation
      between expression of myogenic differentiation marker genes and WT1 levels. We
      conclude that expression of WT1 in C(2)C(12) cells and in rhabdomyosarcoma does
      not inhibit myogenic differentiation.

PMID- 12799192
TI  - Interaction of plasminogen-related protein B with endothelial and smooth muscle
      cells in vitro.
AB  - Plasminogen-related protein B (PRP-B) closely resembles the N-terminal
      plasminogen activation peptide, which is released from plasminogen during
      conversion to plasmin. We have previously demonstrated that the steady-state
      level of mRNA encoding PRP-B is increased within tumor tissues, and that
      recombinant PRP-B antagonizes neoplastic growth when administered systemically to
      mice harboring tumors, but no insights into the cell targets of PRP-B have been
      presented. Employing serum-free medium optimized for culturing human endothelial
      or smooth muscle cells, we show that recombinant PRP-B inhibits basic fibroblast
      growth factor-dependent cell migration for both cell types, as well as tube
      formation of endothelial cells. Comparison with the angiogenesis inhibitors
      angiostatin and endostatin revealed similar results. Recombinant PRP-B is
      effective in promoting cell attachment of endothelial and smooth muscle cells,
      and antibody interference experiments reveal that the interaction of recombinant
      PRP-B with endothelial cells is mediated at least in part by alpha(v)-containing
      integrins. Inhibition of angiogenesis in vivo by PRP-B was demonstrated in the
      chicken chorioallantoic membrane assay. PRP-B and other antiangiogenic molecules
      may elicit metabolic perturbations in endothelial cells as well as perivascular
      mesenchymal cells such as smooth muscle cells and pericytes.

PMID- 12799193
TI  - Telomere maintenance and cell cycle regulation in spontaneously immortalized T
      cell lines from Nijmegen breakage syndrome patients.
AB  - Nijmegen breakage syndrome (NBS) is a rare genetic instability syndrome
      associated with a high incidence of lymphoid malignancies. The NBS1 protein has
      been implicated in telomere biology suggesting that cells from NBS patients might
      have deficient telomere maintenance capacity. In this study we characterized
      spontaneously immortalized T-cell lines derived from three NBS patients regarding
      growth characteristics, telomere biology, expression of cell-cycle regulators,
      and response to DNA damage to understand the role of NBS1 in the immortalization
      process. In all the NBS T-cell lines the acquisition of an immortal phenotype was
      associated with telomere length stabilization, high telomerase activity, and
      increased mRNA expression of the catalytic subunit of telomerase (hTERT),
      together with c-myc up-regulation. Our findings provide evidence that telomere
      length maintenance was intact in the T lymphocytes in the absence of a full
      length NBS protein, presumably due to the presence of an alternatively
      transcribed NBS protein of 70 kDa. Normal protein expression patterns for pRb and
      p53 in all the immortal lines coincided with altered expression of some cell
      cycle proteins as well as with an impaired G1/S arrest after gamma irradiation,
      despite a seemingly normal p53/p21 pathway. The here described, spontaneously
      immortalized NBS derived T-cell lines can be useful in future analysis of the
      biologic effects in the NBS.

PMID- 12799194
TI  - Differential tyrosine phosphorylation of fibroblast growth factor (FGF) receptor
      1 and receptor proximal signal transduction in response to FGF-2 and heparin.
AB  - The sulfated regions in heparan sulfate and heparin are known to affect
      fibroblast growth factor (FGF) function. We have studied the mechanism whereby
      heparin directs FGF-2-induced FGF receptor-1 (FGFR-1) signal transduction. FGF-2
      alone stimulated maximal phosphorylation of Src homology domain 2 tyrosine
      phosphatase (SHP-2) and the adaptor molecule Crk, in heparan sulfate-deficient
      Chinese hamster ovary (CHO) 677 cells expressing FGFR-1. In contrast, for
      phospholipase Cgamma(1) (PLCgamma(1)) and the adaptor molecule Shb to be
      maximally tyrosine-phosphorylated, cells had to be stimulated with both FGF-2 and
      heparin (100 ng/ml). Tyrosine residues 463 in the juxtamembrane domain and 766 in
      the C-terminal tail in FGFR-1 are known to bind Crk and PLCgamma(1),
      respectively. Analysis of tryptic phosphopeptide maps of FGFR-1 from cells
      stimulated with FGF-2 alone and FGF-2 together with heparin showed that FGF-2
      alone stimulated a several-fold increase in tyrosine 463 in the juxtamembrane
      domain. In contrast, heparin had to be included in order for tyrosine 766 to be
      phosphorylated to the same fold level. Our data imply that tyrosine 463 is
      phosphorylated and able to transduce signals in response to FGF-2 treatment
      alone; furthermore, we suggest that FGFR-1 dimerization/kinase activation is
      stabilized by heparin.

PMID- 12799195
TI  - Vaccinia virus complement control protein inhibits hyperacute xenorejection in a
      guinea pig-to-rat heterotopic cervical cardiac xenograft model by blocking both
      xenoantibody binding and complement pathway activation.
AB  - Vaccinia virus complement control protein (VCP) binds the activated third and
      fourth complement components and inhibits both alternative and classical pathways
      of activation. The ability of VCP to bind heparan sulfate allows the protein to
      attach itself to the cell surface, enabling it with many additional activities.
      Altogether, the many functions of VCP have been shown to suppress the
      inflammatory response of the host, helping the vaccinia virus to evade immune
      destruction. VCP has recently been shown to inhibit human anti-Gal alpha1-3 Gal
      antibody attachment to cultured porcine endothelial cells and reduce human
      neutrophil and NK killing of pig aortic endothelial cells through its ability to
      bind heparan sulfate. Here we demonstrate that in an in vivo guinea pig-to-rat
      heterotopic cervical cardiac xenograft model, recombinant VCP (rVCP) is able to
      block hyperacute xenograft rejection, significantly prolonging graft survival.
      Histopathological examination of transplanted hearts from rats receiving rVCP
      revealed a significant reduction in cardiac tissue damage as compared to control
      hearts. Finally, rVCP treated recipients demonstrated marked rVCP deposition on
      the endothelium and significantly less C3, IgG and IgM deposition in the tissue.
      rVCP is therefore able to inhibit hyperacute xenorejection by binding the
      endothelial surface, blocking complement fixation and activation, and preventing
      xenoantibody attachment.

PMID- 12799197
TI  - Co-effect of HLA-G1 and glycosyltransferases in reducing NK cell-mediated pig
      endothelial cell lysis.
AB  - Natural killer (NK) cells play an important role in xenograft rejection. The aim
      of this study was to evaluate the co-effect of human leukocyte antigen (HLA)-G1
      expression and the remodeling of glycoantigens such as the alpha-Gal epitope,
      Galalpha1,3Galbeta1,4GlcNAc-R, by the introduction of glycosyltransferase genes
      related to NK cell-mediated direct cytotoxicity. Human peripheral blood
      mononuclear cells or an NK-like cell line, YT cells, was used as an effector and
      pig endothelial cells (PEC) as the target. A PEC transfectant with HLA-G1 was
      first prepared by the transfection of HLA-G1 and human beta2 microglobulin.
      Several new transfectants were then established by the transfection of
      glycosyltransferase to the HLA-G1 transfectant. The effect of HLA-G1 on NK cell
      mediated PEC lysis was lower than that by the glycosyltransferases. Therefore, in
      the case of the co-transfectants except for HLA-G1+alpha2,6sialyltransferase,
      such as HLA-G1+N-acetylglucosaminyltransferase-III and HLA
      G1+alpha1,2fucosyltransferase, the effect of HLA-G1 expression on NK-mediated
      killing appeared to be accounted for by the transfected glycosyltransferase
      activities and the reduced alpha-Gal expression on the cell surface. However,
      these transfectants showed significant reductions in direct NK cell-mediated
      cytotoxicity, compared with the single HLA-G1 transfectant. The results herein
      suggest that a combination of HLA-G1 and glycosyltransferases has considerable
      potential for the downregulation of NK cell-mediated cytolysis.

PMID- 12799196
TI  - Differential expression of MMP-2/MMP-9 and potential benefit of an MMP inhibitor
      in experimental acute kidney allograft rejection.
AB  - Acute cellular allograft rejection is characterized by leukocyte invasion and
      tissue destruction, associated with qualitative and quantitative alterations in
      the extracellular matrix (ECM) compartment. Metabolism of ECM proteins is mainly
      regulated by matrix metalloproteinases (MMP), that are zinc depended
      endoproteinases. MMP, especially basement membrane degrading MMP-2 and MMP-9,
      also facilitate tissue invasion of leukocytes. In addition, MMP-2 exerts a direct
      pro-inflammatory effect upon glomerular mesangial cells. Therefore, the
      investigation of the role of MMP in transplant rejection may lead to novel
      approaches in the therapy of rejection processes. To our knowledge, this is the
      first study of acute allograft rejection, formally addressing expression and
      activity of MMP, including the effect of a MMP inhibiting agent. For our studies,
      we used the orthotopic kidney allograft model in the stringent Dark Agouti-to
      Lewis rat strain combination. Animals were divided into four groups: group A,
      healthy untreated Lewis rats (n=3); group B, sham operated Lewis rats (n=3);
      group C, transplanted Lewis rats treated with vehicle solution only (n=12); group
      D, transplanted Lewis rats treated with MMP inhibitor BB-94 (n=12). Respective
      animals were treated once daily intraperitonealy with BB-94 (30 mg/kg) or vehicle
      solution only. Treatment lasted from the third preoperative day until the end of
      the experiment, the time of severe rejection at day +7. Acute kidney allograft
      rejection led to alterations in the expression and activity of MMP. Overall MMP
      activity slightly increased despite severe destruction of kidney histology. The
      MMP inhibitor BB-94 successfully inhibited MMP activity to a high extent. MMP
      expression did not show uniform findings, since acute rejection led to
      differential expression of MMP-2 and MMP-9. During the rejection process, MMP-9
      showed a small but significant increase, whereas MMP-2 production decreased
      substantially. Interestingly, BB-94 was able to keep proteinuria at a low level
      in transplanted animals. In conclusion, MMP-especially MMP-9-appear to represent
      new mediators involved in acute kidney transplant rejection.

PMID- 12799198
TI  - Prolongation of liver xenograft survival by adenovirus vector-mediated CTLA-4Ig
      gene transfer.
AB  - Cytotoxic T lymphocyte-associated antigen-4/immunoglobulin fusion products (CTLA
      4Ig), a structural homologue of CD28, has been shown to inhibit cellular and
      humoral immune responses. In this study, we investigated the efficacy of an
      adenovirus vector containing the CTLA-4Ig gene (AdCTLA-4Ig) on recipient survival
      after hamster-to-rat liver xenografting. AdCTLA-4Ig was administrated
      intravenously immediately after grafting. Gene expression was achieved a maximum
      of 7 days after vector injection and continued for more than 4 weeks. The
      proportion of CD25(+) T-cells in recipient lymph nodes was significantly reduced
      7 days after administration of AdCTLA-4Ig, compared to a group given an
      adenoviral vector containing LacZ gene (AdLacZ) or to an untreated control group.
      AdCTLA-4Ig markedly reduced CD2(+) T-cell infiltration into the graft and
      significantly prolonged recipient survival time (9.2+/-4.12 days), compared to
      the untreated group (5.4+/-0.78 days) (P<0.001) and the AdLacZ-treated group
      (5.2+/-0.28 days) (P<0.001). These results indicate that a blockade of T-cell co
      stimulation by AdCTLA-4Ig inhibited T-cell activation and attenuated CD2(+) T
      cell infiltration into the xenograft, resulting in significant prolongation of
      recipient survival time. Thus, AdCTLA-4Ig therapy may provide a novel approach to
      immune regulation.

PMID- 12799199
TI  - Effects of the malononitrilamide FK778 on immune functions in vitro in whole
      blood from non-human primates and healthy human volunteers.
AB  - BACKGROUND: FK778, a malononitrilamide analog of leflunomide, is currently being
      investigated for use in clinical transplantation. METHODS: Whole blood from
      cynomolgus monkeys (n=4) and healthy human volunteers (n=4) was incubated with
      different concentrations of FK778 and stimulated with mitogens in culture medium.
      Lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation
      and by flow-cytometric analysis of expression of proliferating cell nuclear
      antigen on cells in S/G(2)M phase. Flow cytometry was also used to assess
      expression of T and B lymphocyte activation surface antigens and production of
      intracellular cytokines by T cells. RESULTS: Not only lymphocyte proliferation,
      but also expression of various T cell surface antigens (CD25, CD11a, CD95, CD154)
      was suppressed by FK778. Fifty percent effective concentration values for the
      different immune functions were lower in human blood than in blood from
      cynomolgus monkeys. CONCLUSIONS: FK778 inhibits multiple immune functions. Their
      flow cytometric evaluation can be used to assess the effects of the drug in vivo.

PMID- 12799200
TI  - Helper T-cell type 1 or type 2 function of xeno-MHC-restricted T-cell clones in a
      direct xenoantigen recognition.
AB  - There have been several reports that xeno-MHC-restricted T-cells have a cytotoxic
      function through a direct xenoantigen recognition, but yet no report that they
      have a helper function. Previously we showed that both xeno-MHC-restricted CD4(+)
      and CD8(+) T-cells recognized xenoantigens directly in a mouse anti-rat
      combination. In this study, we investigated whether or not xeno-MHC-restricted T
      cells had a helper function. Mouse T-cell clones recognizing rat antigens
      directly were derived from T-cell lines using the limiting dilution method.
      Phenotype, cytotoxic activity and cytokine production of these clones were
      analyzed by flow cytometry, 51Cr release assay and ELISA, respectively. Rat-MHC
      class I-restricted mouse CD8(+) T-cell clones showed a specific cytotoxic
      activity against rat antigens. One CD4(+) clone produced IL-4 and IL-10, and the
      other CD4(+) clone produced not T-helper (Th) 2 cytokine but TNF-alpha. Our
      results suggested that xeno-MHC class I-restricted CD8(+) T-cells should have a
      cytotoxic function, and xeno-MHC class II-restricted CD4(+) T-cells should have
      either Th1 or Th2 function.

PMID- 12799201
TI  - Analysis of AHG-PRA and ELISA-PRA in kidney transplant patients with acute
      rejection episodes.
AB  - Many centers determined a significant correlation between post-transplant anti
      HLA antibodies production and clinical outcome. In order to confirm this
      correlation and ascertain the sequential appearance of anti-HLA antibodies, we
      compared the ELISA (ELISA-PRA) and the anti-human globulin enhanced complement
      dependent lymphocytotoxicity panel-reactive antibodies test (AHG-PRA) with the
      occurrence of acute rejection episodes. Thirty patients who underwent kidney
      transplantation between December 1998 and October 1999 were assayed. One pre
      transplant and 10 post-transplant serum samples were tested from each recipient
      except from one of them who lost his graft on the 1 week post-transplant. The
      diagnosis of acute rejection episode was based on classical criteria (fever,
      graft swelling and tenderness, oliguria, weight gain) and a rapid rise in serum
      creatinine levels, confirmed by an allograft biopsy graded by the Banff working
      classification. The 322 pre- and post-transplant serum specimens were tested by
      AHG-PRA methodology and 298 of them by the ELISA-PRA. The agreement coefficient
      (kappa) for both methodologies was 0.63. There were 27 acute rejection episodes
      in 19 patients. AHG-PRA results were significantly correlated (Hazard
      ratio=10.06; P=0.006) with this occurrence. These data were not confirmed with
      the ELISA-PRA procedure. Our results suggest that a routine post-transplant AHG
      PRA test offers an early risk assessment of acute rejection episodes and may be a
      useful method for monitoring the kidney transplant evolution.

PMID- 12799202
TI  - Chronic cardiac allograft rejection in a rat model disparate for one single class
      I MHC molecule is associated with indirect recognition by CD4(+) T cells.
AB  - T-cell mediated immune responses play a critical role in chronic allograft
      dysfunction. The complex nature of allograft rejection, particularly with respect
      to the vast repertoire of alloantigens and their mode of recognition by T cells,
      presents a major challenge for the design of well-controlled studies into the
      immunobiology of chronic rejection. The purpose of this study was to develop a
      rat model with restricted antigenic specificity that develops chronic rejection
      without any immunologic manipulation to study the T-cell response. PVG.1U
      allogeneic hearts disparate for one single class I antigen, RT.1A(u), were
      transplanted into PVG.R8 rat recipients. Grafts from PVG.R8 were used as
      syngeneic controls. Chronic rejection was studied by histological analysis of the
      grafted hearts at various time points posttransplantation (20-100 days). Donor
      specific alloreactive response was studied in a mixed lymphocyte reaction assay.
      All allografts survived more than 90 days and showed extensive evidence of
      chronic rejection, which was characterized by interstitial fibrosis, vasculitis,
      and occlusive myointimal thickening. Chronic rejection was evident by day 20 and
      most extensive by day 100 posttransplantation. In marked contrast, syngeneic
      grafts remained free of chronic lesions. Lymphocytes harvested from graft
      recipients showed a more vigorous proliferative response to allogeneic
      splenocytes as compared with that of lymphocytes from nai;ve animals. The
      proliferative response was primarily mediated by CD4(+) T cells recognizing the
      RT1.A(a) molecule via the indirect pathway. A single class I disparity in this
      model generates chronic rejection associated with potent CD4(+) T-cell responses
      induced by the indirect recognition pathway. The use of this antigenically
      restricted model may facilitate the design of well-controlled studies for the
      characterization of immune mechanisms responsible for chronic rejection.

PMID- 12799203
TI  - The effect on the proliferation and apoptosis of alloreactive T cells of cell
      dose in a murine MHC-mismatched hematopoietic cell transplantation model.
AB  - Activation-induced cell death (AICD) of lymphocytes is an apoptotic pathway
      involved in the control of T-cell homeostasis. The magnitude of graft-vs.-host
      disease (GVHD) following allogeneic hematopoietic cell transplantation may be
      attenuated by the enhancement of AICD. The aim of the present study was to
      clarify the effect of T cell dose upon the fate (proliferation or apoptosis) of
      individual activated T cells in a murine GVHD model. To this end, we investigated
      the kinetics of the proliferation and apoptosis of donor T cells in recipient
      spleens in the early stage of a fully major histocompatibility complex (MHC)
      mismatched murine transplantation model from C57BL/6 (H-2(b)) to lethally
      irradiated (8.5 Gy) BALB/c (H-2(d)) mice. To track the behavior of alloreactive
      lymphocytes in vivo, we used the fluorescent cytoplasmic dye carboxyfluorescein
      diacetate succinimidyl ester in combination with flow cytometry. Engraftment of
      donor T cells to recipient spleens was almost completed within 24 h after
      transfer. After that, at higher doses of transferred cells, the donor T cells
      actively divided for up to 72 h resulting in a 30-fold increase in cell number at
      the maximum cell dose (2.0 x 10(7)). As the transferred cell dose decreased, the
      proliferation of T cells tended to be suppressed. At cell doses of 0.5 x 10(7) or
      less, the proliferation of T cells was profoundly suppressed, ultimately
      resulting in little proliferation of donor T cells observed from 24 to 72 h at
      the minimum cell dose (0.1 x 10(7)). The frequency of Annexin-V-positive cells
      was found to increase gradually as the transferred cell dose decreased. Thus, an
      increase in apoptotic events appeared to play an important role in the
      suppression of the proliferation of T cells at lower splenocyte doses. Further
      analyses revealed that Fas ligand (FasL)-positive T cells were observed
      exclusively among T cells that divided at least 5 times, and that all of them
      were positive for Annexin-V, indicating that they were in the process of
      apoptosis. Together with our finding that the frequency of apoptosis increased
      with the progression of cell division, these findings strongly suggest that AICD
      occurred through the Fas/FasL system and that AICD increased as the dose of donor
      T cells participating in the allogeneic response decreased. When relatively small
      numbers of T cells are confronted with an excess of antigen, they disappear. This
      process is called clonal exhaustion-deletion. Our results support the idea that
      AICD is involved in the process of clonal exhaustion-deletion. Relevant to the
      clinical aspects of hematopoietic cell transplantation, our findings indicate
      that AICD may be associated with tolerance induction in T-cell-depleted
      transplantation from HLA-mismatched donors, in which T cells contaminating marrow
      grafts do not need to be completely removed for achieving tolerance between
      donors and recipients. Furthermore, our results indicate that a small change in
      the quantitative balance between antigens and T cells responding to them leads to
      a large difference in the fate of T cells activated in response to MHC
      incompatible antigens. Thus, the size of the T cell dose is one of the important
      considerations in tolerance induction, GVHD and rejection.

PMID- 12799204
TI  - The expression patterns of CD44 and CD45RB on peripheral blood T lymphocytes in
      the rejection of allogeneic murine skin transplantation.
AB  - Until now, the rejection was diagnosed through a biopsy, but this method of
      diagnosis reflected the advanced tissue damage of the transplanted organ and
      contained the innate problem of being invasive. In relation, our research
      attempted to evaluate the viability of analyzing the surface antigens of the
      peripheral blood activated T lymphocytes after murine skin transplantation as a
      non-invasive and early diagnostic tool for diagnosis of rejection. After mouse
      skin was transplanted, the expression patterns of activated T lymphocyte markers,
      CD44 and CD45RB were analyzed along with T lymphocyte markers, CD3, CD4 and CD8
      using flow cytometry. The skins from the tails of allogeneic BALB/c(H2d) mice and
      syngeneic C57BL/6J mice were transplanted to C57BL/6J(H2b) mice as test and
      control groups, respectively. Peripheral blood, which was sampled from the tail
      every other day from day 3 to day 15 was stained with anti-CD44 (or CD45RB), anti
      CD4 (or CD8) and anti-CD3 monoclonal antibodies simultaneously, and analyzed by 3
      color FACS. Rejection occurred only in the test group from day 8 to day 13
      (median: day 10). Although the proportions of CD3(+) lymphocytes, CD4(+)
      lymphocytes and CD8(+) lymphocytes showed no difference, the total number of
      peripheral blood lymphocytes and the number of CD3(+) lymphocytes and CD8(+)
      lymphocytes decreased more sharply in the control after day 7. The proportion and
      the number of CD44(+)CD3(+)-lymphocytes, CD44(+)CD4(+)-lymphocytes and
      CD44(+)CD4(+)CD3(+)-lymphocytes began to increase after day 7, to peak on day 11,
      and then to decrease, showing a significant difference. The proportion and number
      of CD44(+)CD8(+)-lymphocytes and CD44(+)CD8(+)CD3(+)-lymphocytes showed similar
      trends. No significant difference was observed in any subsets of the CD45RB
      antigen. The analysis of the expression patterns of surface antigen CD44 on
      peripheral blood T lymphocytes using flow cytometry is sensitive, safe, easily
      repeatable and controllable, and, therefore, can be considered a promising tool
      for the diagnosis of rejection. However, the clear change in CD44 occurred
      between day 9 and day 13, when rejection was observed grossly. Therefore, it is
      regarded more useful as a screening test or follow-up indicator rather than as an
      early diagnostic tool.

PMID- 12799205
TI  - Impact of graft length on surgical damage after intestinal transplantation in
      rats.
AB  - BACKGROUND: Intestinal grafts greatly affect nutrition and immunology in the
      host. The growth of the recipient and incidence of graft-versus-host disease
      depend on graft length. A larger graft may affect the host immune system, but
      little is known about how the length of the intestinal graft severely affects
      surgical intervention. We developed a cervical small bowel transplantation (SBT)
      rat model that minimized technical variations using a cuff method and studied the
      effects of graft length on surgical damage in SBT. MATERIALS AND METHODS: We
      transplanted a whole (70 cm) or partial (15 cm) intestine into a syngeneic rat
      combination of LEW (MHC haplotype: RT1(l)) to LEW and evaluated changes in
      perioperative hemodynamics and the endogenous endotoxin level. Natural killer
      (NK) cell activity in the peripheral blood and the immunologic response of the
      recipient spleen were also studied. RESULTS: In the whole SBT model, body weight
      loss was more severe than in the segmental SBT model; the rats in the former
      model often died, while all in the latter survived indefinitely. The systemic
      blood pressure markedly decreased in the whole SBT group immediately after
      reperfusion. The proliferative activity of splenic lymphocytes stimulated by
      concanavalin A was also more severely inhibited in the former model than in the
      latter postoperatively. NK cell activity in the whole SBT rats declined more
      severely than the segmental SBT rats 3 days postoperatively. CONCLUSION: The
      longer graft severely induced surgical intervention; and influenced host
      immunosuppression, resulting in the higher mortality in rats undergoing whole
      SBT.

PMID- 12799206
TI  - Induction of allograft tolerance through costimulatory blockade: first selection
      of drugs in vitro.
AB  - The development of an in vitro assay predicting the chances of graft survival
      after treatment with immunoregulatory agents is a major topic in transplantation.
      Antibodies (Abs) interfering in the costimulatory pathway are promising
      candidates for the induction of tolerance. To evaluate these antibodies for
      clinical use studies non-human primates are the only feasible option due to
      species specificity of the antibodies. Peripheral blood mononuclear cells,
      isolated from a large panel of rhesus monkeys, were used in a unidirectional
      mixed lymphocyte reaction to evaluate the ability of antibodies blocking the
      costimulatory pathway, to affect both primary and secondary proliferative and
      cytolytic allospecific immune responses in vitro. These blocking antibodies were
      also used in protocols prolonging allograft survival in a life-supporting kidney
      allotransplant model in rhesus macaques. The ultimate aim is to establish a
      correlation between parameters obtained in vitro and the success of
      transplantation in vivo. The combination of anti-CD80 and anti-CD86 resulted in a
      complete abrogation of the primary alloresponse as measured in a proliferation
      assay. Adding anti-CD40 significantly reduced this inhibitory effect although the
      in vivo effects of this antibody have been shown to be beneficial. The secondary
      response was most prominently inhibited by the combination of anti-CD80/86.
      Paradoxically, anti-CD40 alone markedly inhibited the secondary proliferative
      response, but did not add to the inhibitory effect of the combination of anti
      CD80/86. The cytolytic response was inhibited maximally only when CsA was added
      to the combination of anti-CD80/86. Treatment with monoclonal antibodies alone
      without immunosuppressive drugs was sufficient to maintain graft survival during
      the time of treatment in most animals. However, rejection was initiated as soon
      as the treatment ceased and no tolerance, resulting in long-term graft and
      patient survival, was established. The complete inhibition of primary
      alloresponses and the partial inhibition of secondary proliferative alloresponses
      correlate with prolonged graft survival during treatment, but have no predictive
      value for the success of tolerance induction for kidney allografts in rhesus
      monkeys.

PMID- 12799207
TI  - Influence of interleukin-10 polymorphism on the development of coronary
      vasculopathy following cardiac transplantation.
AB  - BACKGROUND: Interleukin-10 (IL-10), an important anti-inflammatory cytokine has
      been implicated in the pathogenesis of acute rejection and long term graft
      tolerance. Polymorphism in the IL-10 promoter at positions -1082, -819 and -592,
      correlates with IL-10 production. Haplotype inheritance of these alleles
      determines whether individuals are high, intermediate, or low producers of IL-10.
      We investigated the effect of this polymorphism on the development of cardiac
      transplant vasculopathy (CV). METHODS: CV was defined at routine surveillance
      coronary angiography as any abnormality in 1 or more epicardial vessels.
      Recipient and donor DNA was amplified by PCR using primers to the 3 allele sites.
      After identifying the phenotype by electrophoresis, freedom from CV was analysed
      by Kaplan-Meier and the log rank test. RESULTS: One hundred and forty eight
      recipients and 135 donors were studied. High, intermediate and low producers made
      up 26.4, 47.3 and 26.3% of recipients and 35.6, 48.2 and 16.2% of donors
      (P=0.42). No significant differences were noted between the phenotype groups. The
      recipient and donor genotypes, when considered in isolation, had no effect on the
      freedom from CV; recipients: P=0.85; donors: P=0.52. When the recipient and donor
      genotypes were combined for an individual patient the freedom from CV was again
      unaffected; high producing IL-10 allele in donor or recipient: P=0.76, low
      producing IL-10 allele in donor or recipient: P=0.51. Increasing donor age and
      acute rejection episodes and the presence of a high producing TGF-beta1 phenotype
      were independent risk factors for CV. CONCLUSIONS: Polymorphism of the IL-10
      promoter region fails to predict the development of CV and cannot be used as a
      genetic risk marker. This may be due to the effects of immunosuppressive
      treatment.

PMID- 12799208
TI  - Invariant Valpha14 NKT lymphocytes: a double-edged immuno-regulatory T cell
      population.

PMID- 12799209
TI  - Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor
      receptor fusion protein for severe sepsis.
AB  - OBJECTIVES: To investigate the effects of Lenercept , a recombinant soluble TNF
      receptor p55 fused to an immunoglobulin heavy chain IgG1, on the balance of pro-
      and anti-inflammatory mediators in sepsis. DESIGN: Post hoc analysis of a
      subgroup of patients enrolled in a multicenter phase III, prospective, double
      blind, placebo-controlled, randomized study of Lenercept in severe sepsis.
      SETTING: Surgical and medical intensive care units, and postoperative recovery
      room of a tertiary care teaching hospital. PATIENTS: A total of 57 patients were
      enrolled in the multicenter study in our center. INTERVENTION: Septic patients
      were randomly assigned to receive either Lenercept 0.125 mg/kg or placebo. The
      patients were followed for up to 28 days after randomization. MEASUREMENTS AND
      MAIN RESULTS: Circulating levels of TNF-alpha, IL-6, TNFsR75 and IL-1Ra were
      measured before and after treatment. The two groups were comparable with regard
      to age, gender and diagnosis distribution. The total level of TNF-alpha increased
      significantly in treated patients, compared to patients receiving placebo. The
      levels of the other inflammatory mediators did not differ between the two groups
      CONCLUSIONS: Lenercept -treated patients experienced a protracted TNF-alpha half
      life, leading to higher total TNF-alpha levels throughout the study. However, the
      treatment had no effects on anti-inflammatory mediators. Therefore, peripheral
      inflammatory processes might not have been significantly modified by the
      treatment. This might account for the lack of efficacy this treatment in septic
      patients

PMID- 12799210
TI  - Carbocysteine lysine salt monohydrate (SCMC-LYS) is a selective scavenger of
      reactive oxygen intermediates (ROIs).
AB  - Carbocysteine lysine salt monohydrate (SCMC-Lys) is a well-known mucoactive drug
      whose therapeutic efficacy is commonly related to the ability of SCMC-Lys to
      replace fucomucins by sialomucins. The aim of this study was to determine if SCMC
      Lys could exert an anti-oxidant action by scavenging reactive oxygen
      intermediates (ROIs). Our results show that SCMC-Lys proved effective as a
      selective scavenger of hypochlorous acid (HOCl) and hydroxyl radical (OH.), this
      effect being related to the reactivity of the SCMC tioether group. The scavenger
      activity of SCMC-Lys was observed in free cellular system as well as in activated
      human polymorphonuclear neutrophils (PMNs). SCMC-Lys scavenger activity on HOCl
      was paralleled by a powerful protection from HOCl-mediated inactivation of alpha1
      antitripsin (alpha1-AT) inhibitor, the main serum protease inhibitor. Production
      of interleukin-(IL-)8, a major mediator of PMN recruitment in inflammatory
      diseases, is known to be mediated by intracellular OH. SCMC-Lys significantly
      reduced IL-8 production on stimulated human peripheral blood mononuclear cells
      (PBMCs) in the same range of concentrations affecting OH. activity. It is
      concluded that SCMC-Lys could exert, in addition to its mucoactive capacity, an
      anti-oxidant action, thus contributing to the therapeutic efficacy of SCMC-Lys.

PMID- 12799211
TI  - Over expression of interleukin-1alpha, interleukin-1beta and interleukin-1
      receptor antagonist in testicular tissues from sexually immature mice as compared
      to adult mice.
AB  - The levels of IL-1alpha, IL-1beta and IL-1Ra were higher in homogenates of
      testicular tissue from sexually immature than those from mature mice.
      Immunohistochemical staining of testicular tissues from sexually immature and
      adult mice show that differentiated germ cells express higher levels of IL-1alpha
      compared to Sertoli cells and Leydig cells/interstitial cells. Peritubular cells
      of sexually immature and adult mice did not express IL-1alpha. Testicular tissue
      cells of adult mice showed high levels of expression of IL-1beta, mainly in the
      cytoplasm and nucleus of the spermatogonia and in spermatocytes. Sertoli cells
      and Leydig/interstitial cells were also highly stained for IL-1beta. However,
      peritubular cells did not express IL-1beta. On the other hand, testicular tissue
      cells from sexually immature mice, showed high levels of IL-1beta, mainly in
      spermatocytes. Spermatogonia showed low levels of IL-1beta expression. Also, high
      levels of IL-1beta expression were detected in Leydig/interstitial cells.
      Peritubular cells clearly showed IL-1beta expression. Testicular tissue cells
      from adult mice, showed IL-1Ra expression in spermatogonia, Sertoli and
      Leydig/interstitial cells. IL-1Ra expression was clearly present in the Golgi
      apparatus of spermatogonia and Sertoli cells. However, peritubular cells did not
      show IL-1Ra expression. Testicular tissue cells from sexually immature mice, also
      showed high levels of IL-1Ra expression mainly in the cytoplasm and nucleus of
      the spermatogonia and Sertoli cells. In addition, Leydig/interstitial cells and
      peritubular cells also expressed IL-1Ra. Our results demonstrate, for the first
      time, the expression of IL-1beta in germ and Sertoli cells, and IL-1Ra in
      Leydig/interstitial cells of testicular tissues from adult and sexually immature
      mice, under in vivo conditions. In addition, the relative elevated levels of the
      IL-1 system in the testis of immature mice compared to mature mice may indicate
      its involvement in the spermatogenesis.

PMID- 12799212
TI  - T cell cytokine profile during primary Epstein-Barr virus infection (infectious
      mononucleosis).
AB  - Cytokine profiles of CD4+ and CD8+ T-cell subsets were evaluated in 8 patients
      with infectious mononucleosis (IM). Intracellular detection of cytokines using
      flow cytometry revealed an expansion of IFN-gamma-expressing CD4+ T cells, and
      particularly CD8+ T cells, while IL-2 expressing cells were less frequently
      encountered when compared to healthy controls. Single TNF-alpha-expressing CD4+
      and CD8+ T cells were likewise reduced and shifted towards IFN-gamma/TNF-alpha co
      production. The predominant pro-inflammatory type 1-biased immune response during
      IM was emphasized by low frequencies of IL-10 expression in both T cell subsets,
      although some patients displayed elevated serum levels. Six months later, a
      decreased, but still elevated IFN-gamma expression within the CD8+ T cell subset,
      and an increased percentage of IL-2-expressing CD4+ and CD8+ T cells, reaching
      values shown for controls, were noted. Type 2-associated cytokines such as IL-4
      and IL-13, as well as IL-6 and TNF-alpha were not significantly different when
      compared to controls at study entry and at follow-up. The striking expansion of
      IFN-gamma-producing CD8+ T cells with rather low expression of IL-10, appears to
      be a key factor for clinically overt disease, but is nevertheless compatible with
      successful control of the viral infection.

PMID- 12799213
TI  - Circulating angiogenic cytokines in multiple myeloma and related disorders.
AB  - We investigated the serum concentrations of selected angiogenic cytokines
      including: vascular endothelial growth factor (VEGF), hepatocyte growth factor
      (HGF), transforming growth factor beta 1 (TGF-beta1) and basic fibroblast growth
      factor (bFGF) in 162 patients with multiple myeloma (MM), 5 patients with
      Waldenstr m's macroglobulinaemia (WM), and 31 healthy controls. Among the MM
      patients there were 2 cases of primary plasma cell leukemia (PCL) and one case of
      extramedullary plasmacytoma. The levels of measured cytokines were correlated
      with the phase and stage of the disease as well as the most important clinical
      and laboratory parameters associated with disease activity (haemoglobin,
      creatinine, albumins, calcium, M-component, CRP,beta2m, LDH and bone
      involvement). We have found correlations between serum levels of angiogenic
      cytokines and some parameters depicting the disease activity and advancement. The
      serum level of VEGF in MM patients (median 244.5 pg/mL) correlated with serum
      concentrations of beta-2-microglobulin (beta2m) greater than 2.5 mg/L (p =
      0.0005) and abnormal values of lactate dehydrogenase (> 425 U/L, median   329.0
      pg/mL and < 210 U/L, median   426.6 pg/mL, p = 0.004 and p = 0.04 respectively).
      MM patients in stage III had higher serum levels of HGF (median   1 411.3 pg/mL)
      than those in stage I (median   1 219 pg/mL) (p = 0.01) according to Durie and
      Salmon staging, and those in phase I (at diagnosis) (median 1 555.6 pg/mL) and
      phase III (in progression) (median 1 309.7 pg/mL) had higher levels than those in
      phase II (plateau phase) (median 1 047.9 pg/mL) (p = 0.002 and p = 0.02
      respectively). Significantly elevated values of HGF were found in MM patients
      with anaemia (median   1 962.0 pg/mL) and hypercalcaemia (median   2 085.6 pg/mL)
      (p = 0.00001 and 0.04 respectively). TGF-beta1 (median   33.9 ng/mL) correlated
      positively with highbeta2m values (> 2.5 mg/L) (p = 0.04) and was significantly
      higher in phase I (median   40.1 ng/mL) than in phase II (median   30.9 ng/mL) (p
      = 0.03) of the disease. The concentration of bFGF was significantly higher in
      stage III of MM (median   3.1 pg/mL) than in stage I (median   1.2 pg/mL) (p =
      0.04). We found that the survival probability was statistically higher for newly
      diagnosed MM patients with a concentration of VEGF lower than the median value
      for this cytokine. The concentrations of the cytokines analyzed in patients with
      Waldenstr m's macroglobulinaemia (WM), primary plasma cell leukaemia (PCL) and
      non-secretory (NS) myeloma were not distinguishable from those found in MM
      patients. We also studied the relationship between the levels of cytokines
      analyzed and found positive correlations between bFGF and TGF-beta1 (rho = 0.183,
      p < 0.02), as well as VEGF and TGF-beta 1 (rho = 0.537, p < 0.001) and VEGF and
      bFGF (rho = 0.197, p < 0.02). In conclusion, our data indicate a strong
      relationship between angiogenic cytokine serum levels and clinical course as well
      as selected laboratory parameters of patients with MM.

PMID- 12799214
TI  - LPS and Freund's adjuvant initiate different inflammatory circuits in
      experimental autoimmune thyroiditis.
AB  - Although adjuvants are essential for the initiation of experimental autoimmune
      diseases, their precise contribution to the pathological manifestations is still
      poorly understood. Experimental autoimmune thyroiditis (EAT) is interesting in
      that respect because it can be initiated with the help of two different adjuvants
      Freund's complete or LPS   which may initiate independent pathogenic pathways.
      In the present study, we have compared Freund's-induced versus LPS-induced EAT
      with respect to their dependence upon CD8+ T cells, which are considered as major
      actors in the pathogenesis of thyroiditis. Our results reveal that whereas CD8+ T
      cells are mandatory in the Freund's model, they can be bypassed in the LPS model.
      On the basis of this finding, we have examined the possibility that LPS may act
      directly upon in vitro cultured thyrocytes with no intermediate cell stages.
      Indeed, LPS triggers transcription and protein synthesis of several chemokines
      such as MIP-3alpha, RANTES, MCP-1 or TARC. Thus, beside enhancing the
      immunogenicity of autoantigens, probably via antigen trafficking and
      presentation, adjuvants such as LPS directly interact with the target organ
      through synthesis and release of powerful T cell attractants that facilitate its
      lymphocytic infiltration.

PMID- 12799215
TI  - Wound healing mediator production by human dermal fibroblasts grown within a
      collagen-GAG matrix for skin repair in humans.
AB  - Cell and tissue therapy applications in humans are being used increasingly,
      particularly for tissue repair. Several reconstructed skin models have been
      proposed. Wound healing involves overlapping steps of inflammation, cell
      migration and proliferation, neovascularisation, extracellular matrix production
      and remodelling. This is regulated by numerous cytokines and other soluble
      mediators. We have prepared dermal substitutes (DS) consisting of a collagen-GAG,
      three-dimensional matrix colonized by human dermal fibroblasts (HDF), isolated by
      skin explant or enzymatic digestion of the skin for potential therapeutic use in
      humans. To test the functionality of these DS, we measured (ELISA) the
      stimulatory effect on HDF in the matrix, of serial dilutions of human serum (HS)
      on the production of wound healing mediators: interleukin-8 (IL-8), vascular
      endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1). We observed: 1). a stimulatory effect
      of HS on HDF production of the different mediators tested, with a dose-dependent
      effect in the case of IL-8 and VEGF. 2). A matrix-potentiating effect on the
      production of the different mediators by HDF. 3). A decrease in the production of
      IL-8 and VEGF when HDF isolated by enzymatic digestion was used to colonize the
      matrix as compared with HDF isolated by skin explant. We conclude: 1). that the
      production by HDF, in a collagen-GAG matrix, of mediators involved in cutaneous
      wound healing is decreased when HDF are isolated by enzymatic skin digestion
      rather than by skin explant. 2). That measurement of the production of cytokines
      or other mediators could be a useful quality control to test the functionality of
      tissue-engineered DS for tissue repair therapy in humans and more generally of
      cells prepared for cell therapy.

PMID- 12799216
TI  - Undetectable levels of tumor necrosis factor-alpha, nitric oxide and inadequate
      expression of inducible nitric oxide synthase in congenital hypothyroidism.
AB  - OBJECTIVE: To analyse the production of TNF-alpha and NO in euthyroid and
      hypothyroid newborns. PATIENTS: A cross-sectional study was conducted involving
      10 newborns diagnosed with primary congenital hypothyroidism (CH; group A) and 10
      euthyroid children (group B). RESULTS: There were undetectable plasma levels of
      TNF-alpha and NO in the hypothyroid children, however plasma levels of TNF-alpha
      (5.5 0.5 pg/ml) and NO (5.6 1.7 microM) were detected at normal levels in all
      euthyroid children. Moreover, expression of iNOS mRNA in PBMC, determined by RT
      PCR, was negative in both groups of infants. CONCLUSION: TNF-alpha and NO
      production are both impaired in hypothyroid newborns. We report for the first
      time evidence of undetectable levels of TNF-alpha and NO in infants with CH.

PMID- 12799220
TI  - Chlamydia pneumoniae seropositivity and the risk of NAION.

PMID- 12799221
TI  - Darkness and myopia progression.

PMID- 12799226
TI  - Fluorometholone in children.

PMID- 12799228
TI  - What is HIPAA and what effect may it have on our journal?

PMID- 12799229
TI  - Quality of life associated with visual loss: a time tradeoff utility analysis
      comparison with medical health states.
AB  - PURPOSE: To assess the visual utility values of patients with ocular disease and
      to compare these values with those of patients with systemic health states
      DESIGN: Cross-sectional utility value assessment. METHODS: Consecutive patients
      with ophthalmic diseases were interviewed in a one-on-one fashion using a
      standardized time tradeoff utility value assessment form. These values were
      compared with utility values for systemic health states present in the
      literature. INTERVENTION: None. MAIN OUTCOME MEASURE: Time tradeoff utility value
      on a scale ranging from 1.0 (perfect visual health) to 0.0 (death). The
      ophthalmic patient groups were stratified into 4 visual groups dependent on the
      visual acuity in the better-seeing eye. The groups were as follows: group 1,
      20/20 to 20/25; group 2, 20/30 to 20/50; group 3, 20/60 to 20/100; group 4,
      20/200 to no light perception. RESULTS: A total of 500 subjects were enrolled in
      the study. The mean utility values for the visually stratified groups were: group
      1, 0.88; group 2, 0.81; group 3, 0.72; group 4, 0.61. Comparable respective
      systemic health state utility values for each of the ophthalmic groups were:
      diabetes mellitus, status after kidney transplantation, moderate stroke, and
      moderately severe stroke. CONCLUSIONS: Visual loss is associated with a
      substantial and measurable diminution in quality of life. This diminution in
      quality of life can be directly compared with that induced by systemic health
      states.

PMID- 12799230
TI  - Do motor vehicle airbags increase risk of ocular injuries in adults?
AB  - PURPOSE: This study was undertaken to evaluate the risk of eye injury in motor
      vehicle accidents in which airbags deploy. An attempt was made to assess the
      possible associations between eye injuries and eyewear in these accidents.
      DESIGN: Retrospective observational case series and literature review with
      analysis. PARTICIPANTS/METHODS: We conducted a literature review of 62 case
      reports and articles describing 110 adult cases of eye injury after deployment of
      an airbag and examined two Finnish accident cohorts. The fatal accident series
      (FAS; fatal injuries with one or more cars involved) included 121 individuals
      sitting behind an airbag that deployed (65 survivors), and the Airbag study (AB;
      nonfatal, relatively serious accidents) included 210 individuals (survivors).
      MAIN OUTCOME MEASURES: The type of eye injury, eyewear, and crash dynamics were
      studied in each of the reviewed case reports. The fatal accident series and AB
      studies were analyzed to disclose the eye injuries and use of eyewear and to
      estimate their possible relation to deployment of airbags. RESULTS: Analysis of
      the published reports revealed that airbag-induced eye injuries were not more
      frequently reported among wearers of eyeglasses than among nonwearers. However,
      open-eye injuries were reported three times more often among eyeglass wearers (P
      = 0.04), whereas all injuries from airbag chemicals occurred among nonwearers.
      With the exception of one orbital fracture with hyphema, all eye traumas (n = 7)
      in the FAS and AB cohorts were mild (eyebrow laceration, lid contusion,
      bruising). The risk of airbag-related eye injury was 2.5% for any eye injury and
      0.4% for severe eye injury. In single accidents when seat belts were used, the
      risks were 2.0% and 0.5%, respectively. In the accidents from the FAS data no
      difference was observed in the risk for eye injury between survivors in incidents
      involving airbag deployment and incidents not involving airbags. This risk was
      not found to be greater among eyeglass wearers. CONCLUSIONS: Despite reported
      cases in the literature, we found that the risk of severe eye injury from airbags
      was very low (0.4%) in fatal or relatively serious accidents. Eyewear did not
      seem to increase this risk but might interfere with the injury pattern.

PMID- 12799231
TI  - Epidemiologic study of age-related cataracts among an elderly Chinese population
      in Shih-Pai, Taiwan.
AB  - PURPOSE: The purpose of this study was to determine the prevalence and risk
      factors for age-related cataracts in a metropolitan elderly Chinese population in
      Shihpai, Taipei, Taiwan. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: A total of 2045 subjects at least 65 years of age were invited to
      participate, and 1361 (66.6%) participated in the survey. METHODS: An eye
      examination, including lens opacity grading, was conducted by ophthalmologists
      using the Lens Opacity Classification System III (LOCS III). A structured
      questionnaire was used for data collection. Interviewers also collected
      information on subjects' blood pressure, lifestyle (cigarette smoking and alcohol
      intake), medical history, and waist and hip circumferences. MAIN OUTCOME
      MEASURES: Subjects were defined as having age-related cataracts if there was any
      type of lens opacity with an LOCS III grade of more than 2 in one or both eyes.
      When both eyes of an individual had age-related cataracts, the more affected eye
      was used for analysis. RESULTS: Among the 1361 participants, 806 were diagnosed
      with age-related cataracts. The prevalence was 59.2% (95% confidence interval,
      56.6%-61.8%). Women had a higher prevalence of cataracts than men (64.0% vs.
      56.1%, P = 0.004). The prevalence of age-related cataracts increased with age (P
      = 0.001). Nuclear opacity was the most prevalent type (38.9%), followed by
      cortical opacity (21.9%) and posterior subcapsular opacity (9.2%). On the basis
      of the final logistic regression model, after controlling for all other
      covariates, increased age and female gender were factors that were associated
      with an increased risk for all types of cataracts. Besides age and gender, the
      most significant risk factor for nuclear cataracts was current cigarette smoking;
      the significant predictors for cortical cataracts were higher systolic blood
      pressure, a history of cigarette smoking in the past, and history of diabetes;
      the significant predictor for posterior subcapsular cataracts was higher systolic
      blood pressure. CONCLUSIONS: The increasing prevalence of age-related cataracts
      with age highlights the need to seek appropriate medical services and for
      preventative interventions. Elderly people often ignore the importance of seeking
      vision services and care to prevent blindness or visual impairment. These
      findings suggest that the elderly need to be educated regarding the importance of
      eye care by physicians and hygiene authorities in Taiwan.

PMID- 12799232
TI  - Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai
      Eye Study.
AB  - PURPOSE: To describe the epidemiology of dry eye in an elderly Chinese population
      in Taipei, Taiwan. DESIGN: A population-based cross-sectional study.
      PARTICIPANTS: The Shihpai Eye Study was a population-based survey of eye diseases
      in the elderly (> or =65 years) in Shihpai, Taipei, Taiwan. Noninstitutionalized
      residents, as of July 1999, were identified by using the official household
      registration database. A total of 2045 subjects were selected, and 1361 (66.6%)
      people participated in the study. Among them, 822 (60.4%) were men. METHODS:
      Trained interviewers administered a standardized questionnaire pertaining to dry
      eye symptoms. Objective examinations of dry eye included tear film breakup time,
      Schirmer test, fluorescein stain of the cornea, and anatomic assessment of the
      meibomian glands via slit-lamp biomicroscopy. MAIN OUTCOME MEASURES: Frequency of
      dry-eye symptoms and positive dry-eye tests. RESULTS: In this population, 33.7%
      (459/1361) were symptomatic, defined as reporting 1 or more dry-eye symptoms
      often or all of the time. Women were more likely to report frequent symptoms of
      dry eye (odds ratio, 1.49; 95% confidence interval, 1.19-1.87). Among those who
      were symptomatic, 78.9% (362/459) had a low tear film breakup time (< or =10
      seconds), 62.5% (287/459) had a low Schirmer test result (< or =5 mm), and 61.7%
      (283/459) had abnormal anatomic features of the meibomian glands. Furthermore,
      85.4% (392/459) were symptomatic and had either a low Schirmer score or an
      abnormal meibomian gland assessment. Of those symptomatic, 49.9% (229/459)
      indicated that they had visited an eye doctor, 5.4% (25/459) responded that they
      had been diagnosed with dry eye, and 47.5% (218/459) reported current use of
      eyedrops. CONCLUSIONS: This is the first report of population-based data of dry
      eye that includes symptoms and signs in elderly Asians. The prevalence of dry
      eye, although varied according to definition, is relatively higher in this study
      than that reported for whites. Further studies are needed to determine whether
      this is due to racial or environmental factors.

PMID- 12799233
TI  - Assessing the severity of keratitis sicca with videokeratoscopic indices.
AB  - PURPOSE: To determine the correlation between the regularity indices of the Tomey
      TMS-2N computerized videokeratoscopy (CVK) instrument (Tomey, Waltham, MA) with
      conventional measures of dry eye symptoms and disease. DESIGN: A retrospective,
      clinic-based, case-control study. PARTICIPANTS: A total of 16 eyes of 16
      asymptomatic normal subjects and 74 eyes of 74 patients with reports of ocular
      irritation. METHODS: Corneal surface regularity and potential visual acuity
      indices of the Tomey TMS-2N CVK instrument were evaluated in patients with ocular
      irritation symptoms and in normal subjects. MAIN OUTCOME MEASURES: The surface
      regularity index (SRI), surface asymmetry index (SAI), potential visual acuity
      index (PVA), and irregular astigmatism index (IAI) of the Tomey TMS-2N were
      compared between normal and dry-eye patients. Severity of dry-eye symptoms was
      assessed with a validated questionnaire. Schirmer 1 test (without anesthesia),
      biomicroscopic meibomian gland evaluation with a composite severity score (MGD
      score), fluorescein tear break-up time (TBUT), and corneal fluorescein staining
      were performed. The correlations between CVK indices of the Tomey TMS-2N and the
      symptom severity score, Schirmer 1 test, MGD score, TBUT, and corneal fluorescein
      staining score were studied. RESULTS: Dry-eye patients had greater mean symptom
      severity scores, lower Schirmer 1 test scores, greater MGD scores, more rapid
      TBUT, and greater total corneal fluorescein staining scores (P < 0.001 for all
      parameters). The SRI, SAI, and IAI were all significantly greater in dry-eye
      patients than normal subjects. These were 0.46 +/- 0.36 (normal) versus 1.09 +/-
      0.76 (dry) for the SRI (P = 0.0017), 0.30 +/- 0.15 (normal) versus 0.90 +/- 1.09
      (dry) for the SAI (P = 0.0321), and 0.42 +/- 0.28 (normal) versus 0.56 +/- 0.24
      (dry) for the IAI (P = 0.0321). The PVA index was significantly lower in the dry
      eye patients (0.89 +/- 0.13) than normal eyes (0.68 +/- 0.23; P = 0.0008). The
      SRI, SAI, and IAI were positively correlated with total and central corneal
      fluorescein staining scores (P < 0.00001 for all indices). An SRI (> or =0.80),
      SAI (> or =0.50), and IAI (> or =0.50) had sensitivities in predicting total
      corneal fluorescein staining (score > or = 3) of 89%, 69%, and 82%, respectively.
      The specificity of these indices was 80%, 78%, and 82%, respectively. In all 90
      eyes, the mean SRI was greater in subjects older than 50 years (P = 0.012)
      compared with younger patients, whereas no age effect was noted in the dry-eye
      patients. The SRI and PVA index showed better correlation with symptoms of
      blurred vision than the best-corrected visual acuity. CONCLUSIONS: Patients with
      ocular irritation have an irregular corneal surface that may contribute to their
      irritation and visual symptoms. Because of their high sensitivity and
      specificity, the regularity indices of the Tomey TMS-2N have the potential to be
      used as objective diagnostic indices for dry eye, as well as a means to evaluate
      the severity of this disease.

PMID- 12799234
TI  - Tear function and ocular surface changes in keratoconus.
AB  - PURPOSE: To describe the ocular surface disorder in patients with keratoconus.
      DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-five eyes of
      38 patients with keratoconus seen at Uludag University School of Medicine,
      Department of Ophthalmology, from March 2000 through April 2001, and 80 eyes of
      40 normal control subjects were studied. INTERVENTION: The subjects underwent
      routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test,
      tear film breakup time (BUT), fluorescein and rose bengal staining of the ocular
      surface, and conjunctival impression cytology. MAIN OUTCOME MEASURES: Patients
      and control subjects were compared for corneal sensitivity, tear function, ocular
      surface staining parameters, goblet cell density, and squamous metaplasia grade.
      The relation of these parameters to the severity of keratoconus progression was
      also investigated. RESULTS: The mean corneal sensitivity was significantly lower
      in keratoconus patients compared with control subjects (P < 0.001). The BUT
      values were also significantly lower in the keratoconus group. Patients with
      keratoconus had significantly higher fluorescein and rose bengal staining scores
      (P < 0.001). Corneal sensitivity and tear function changes seemed to get worse
      with advanced stages of keratoconus. Impression cytology showed goblet cell loss
      and conjunctival squamous metaplasia, both of which again related to the extent
      of progression of keratoconus. CONCLUSIONS: The ocular surface disease in
      keratoconus is characterized by disorder of tear quality, squamous metaplasia,
      and goblet cell loss, all of which seem to relate to the extent of keratoconus
      progression.

PMID- 12799235
TI  - Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after
      penetrating keratoplasty.
AB  - PURPOSE: To determine visual results and report side effects and complications
      after phototherapeutic keratectomy (PTK) for BIGH3-linked corneal dystrophy
      recurring after penetrating keratoplasty. DESIGN: Retrospective noncomparative
      case series. PARTICIPANTS: Forty-two excimer laser PTK procedures were performed
      in 42 eyes of 29 patients with BIGH3-linked corneal dystrophies. Genetic status
      of all patients was determined and allowed us to assess an unambiguous diagnosis.
      Preoperative diagnoses included LCDIIIA/A546T (1 eye), R124 l+DT125-DE126 (4
      eyes), GICD/R555W (14 eyes), LCDI/R124C (6 eyes), SGD/R124 l (16 eyes), and
      CDBII/R555Q (1 eye). INTERVENTION: Two excimer lasers (Summit Excimed UV 200,
      Summit Technology, Waltham, MA and Nidek EC 5000, Nidek, Inc., Gamagori, Japan)
      were used to perform all PTKs. Indications for performing PTK after a graft were
      severe decrease of the best-corrected visual acuity (BCVA) related to recurrent
      corneal deposits and/or painful recurrent epithelial erosions. MAIN OUTCOME
      MEASURES: Preoperative and postoperative BCVA were analyzed, significant
      recurrences after treatment were noted, and postoperative complications were
      recorded. RESULTS: Mean preoperative BCVA was 0.2 +/- 0.12 in the decimal chart,
      mean postoperative BCVA was 0.52 +/- 0.16 with a mean follow-up of 3.13 +/- 1.77
      years (range, 0.3-6.65 years). Visual acuity was significantly improved after
      surgery (P < 0.05). The magnitude of the change in visual acuity was dependent on
      the mutation (P < 0.001). Seven symptomatic recurrences were observed. One
      regressive graft rejection and 4 cases of severe postoperative haze were
      observed. No other complications were noted. CONCLUSIONS: PTK is a simple, safe,
      and efficient technique for the treatment of recurrent corneal dystrophies; in
      many cases it prevents or delays the major incumbent problems of repeated
      grafting.

PMID- 12799236
TI  - Tectonic corneal lamellar grafting for severe scleral melting after pterygium
      surgery.
AB  - PURPOSE: To describe the technique and review the indications and success of
      tectonic corneal lamellar grafting for the management of severe scleral melts
      after pterygium surgery. DESIGN: Retrospective, noncomparative, interventional
      case series. PARTICIPANTS: Twenty cases of severe scleral necrosis after
      pterygium surgery (1993-1999). INTERVENTION: Tectonic corneal lamellar grafting.
      Surgery involved (1) removal of all devitalized or infected scleral tissue
      surrounding the melt; (2) use of lamellar or full-thickness donor corneal tissue,
      fashioned to fit the scleral defect exactly or a 0.25-mm diameter larger; and (3)
      placement of a pedicled or free conjunctival flap over the corneal lamellar
      graft. MAIN OUTCOME MEASURES: Eradication of progressive scleral necrosis,
      preservation of globe integrity, eradication of infection, and preoperative and
      postoperative visual acuity. RESULTS: Sixteen (80%) of 20 cases developed severe
      scleral necrosis that required tectonic surgery after bare sclera pterygium
      excision with mitomycin C or beta-irradiation. Surgery was also therapeutic to
      eradicate progressive infection in 6 cases of infective scleritis that did not
      respond to maximal medical treatment. Scleral melting presented 1 month to 20
      years after initial pterygium surgery in healthy, immune-competent adults.
      Therapeutic and tectonic success was achieved in 19 cases (95%); in 1 case,
      recurrence of fusarium fungal infection led to severe graft necrosis and
      intraocular spread. Among the cases of infectious scleritis, three eyes required
      repeat lamellar grafting to successfully eradicate infection. CONCLUSIONS:
      Tectonic and therapeutic lamellar keratoplasty, combined with aggressive
      antibiotic therapy, preserved globe integrity and eradicated infection in cases
      of severe scleral melting after pterygium surgery.

PMID- 12799237
TI  - Conjunctival ulcers in Behcet's disease.
AB  - PURPOSE: To describe the occurrence of conjunctival ulcers as a manifestation of
      Behcet's disease. DESIGN: Retrospective, noncomparative, interventional case
      series with histopathologic correlation. METHODS: Six patients who fulfilled the
      diagnostic criteria for Behcet's disease and presented with painful conjunctival
      ulcers were included in the study. Three of these ulcers were biopsied and
      studied histologically and immunohistochemically. The lesions were treated with
      topical or subconjunctival injection of corticosteroids and, in one case, with
      oral indomethacin. RESULTS: Although all six patients fulfilled the diagnostic
      criteria for Behcet's disease, two developed uveitis and other signs of Behcet's
      disease only months to years after the appearance of the conjunctival ulcers. The
      3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar
      conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both
      acute and chronic inflammatory cells, and high endothelial venules.
      Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T
      cell populations admixed with several B cells and CD68-positive histiocytes.
      After treatment, the conjunctival lesions invariably healed without scarring.
      CONCLUSIONS: In addition to the oral and genital ulceration, ulcers can also be
      found in the conjunctiva of patients with Behcet's disease. Although this is a
      rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may
      suggest a diagnosis of Behcet's disease.

PMID- 12799238
TI  - Technique for removal of a capsular tension ring from the vitreous.
AB  - PURPOSE: To report a new technique for safely and quickly removing a displaced
      capsular tension ring from the vitreous cavity. DESIGN: Two interventional case
      reports. PARTICIPANTS: The authors retrospectively reviewed the charts of two
      patients with displaced capsular tension rings (CTRs). INTERVENTION: Surgical
      removal of the displaced CTRs was performed in two patients. MAIN OUTCOME
      MEASURES: Visual and anatomic outcomes. RESULTS: The CTRs were removed
      surgically, in case 1 by cutting the CTR into two pieces before removal and in
      case 2 by using the CTR injector to remove the CTR in one piece through a
      sclerotomy site. Both patients had good visual and anatomic outcomes.
      CONCLUSIONS: The described technique of removing a displaced CTR in one piece
      through a sclerotomy site using the CTR injector provides a safe and efficient
      method of CTR removal. Cutting the CTR into two or more pieces for removal is not
      recommended.

PMID- 12799239
TI  - Comparison of data analysis tools for detection of glaucoma with the Heidelberg
      Retina Tomograph.
AB  - PURPOSE: To evaluate the performance of three linear discriminant functions
      (LDFs) and the Moorfields Regression Analysis (MRA) in classifying optic disc
      topography images obtained with the Heidelberg Retina Tomograph (HRT) from
      patients with open-angle glaucoma and normal controls. Furthermore, to
      investigate whether the classification of glaucomatous eyes is related to the
      severity of visual field loss or to optic disc size. DESIGN: Prospective
      comparative observational case series. PARTICIPANTS: One eye of 104 patients with
      a diagnosis of open-angle glaucoma (mean age, 63.2; range, 30-88 years) and 48
      normal controls (mean age, 52.4; range, 33-75 years). TESTING: Subjects were
      examined with the HRT. MAIN OUTCOME MEASURES: Diagnostic performance was
      calculated for the LDFs published by Mikelberg et al (LDF1), Burk (LDF2), and
      Bathija et al (LDF3) and for the MRA. RESULTS: Large differences in sensitivity
      and specificity were found among the different analyses when using the originally
      suggested cutoff criteria. When specificity was equalized to 90%, the
      sensitivities were more similar (LDF1, 55%; LDF2, 61%; and LDF3, 67%). At 95%
      specificity, the sensitivities decreased further (LDF1, 39%; LDF2, 55%; LDF3,
      44%). When treating the "borderline" outcomes as test positives, MRA sensitivity
      and specificity were 78% and 81%, respectively. When treating the "borderline"
      outcomes as test negatives, the MRA gave a sensitivity of 58%, with a specificity
      of 96%. In glaucoma patients, the correlation between the severity of visual
      field damage, as measured by the mean deviation index, and the outcome of the
      classification systems was low to moderate (Spearman's r between 0.26 and 0.39).
      When the entire sample was stratified into equal thirds on the basis of optic
      disc size, large discs (area > 2.10 mm(2)) tended to be classified with a higher
      sensitivity but lower specificity than small discs (area < 1.73 mm(2)) with all
      methods except LDF3. Using a multiple regression model controlling for mean
      deviation, LDF1, and LDF2, but not LDF3, were significantly influenced by disc
      size. CONCLUSIONS: The 4 methods of analysis had similar sensitivities once their
      specificities were equalized. In this sample, the LDFs and MRA generally did not
      discriminate between glaucoma patients and controls as well as reported in the
      original respective studies that described the methods.

PMID- 12799240
TI  - Visual acuity loss and clinical observations in a large series of patients with
      Stargardt disease.
AB  - PURPOSE: To assess visual acuity impairment in Stargardt disease. DESIGN:
      Retrospective clinic-based cross-sectional study. PARTICIPANTS: Three-hundred
      sixty-one patients with Stargardt disease. METHODS: Clinical findings in 361
      patients were analyzed as part of a cross-sectional evaluation. Visual acuity at
      their most recent visit, fundus photographs, and electroretinographic findings
      were reviewed, and patients were categorized into four clinical phenotypes.
      Seventy-three patients with 20/40 or better vision and 38 patients with 20/50 to
      20/100 vision in the better seeing eye at their initial visit who were followed
      for at least 1 year were included in a survival analysis. For analysis purposes,
      these latter patients were categorized into four 20-year age groups according to
      their age at initial visit. MAIN OUTCOME MEASURES: Best-corrected visual acuity
      from the eye with better vision on the most recent visit was used in the cross
      sectional analysis. For the survival analysis, best-corrected visual acuity was
      used from the eye with better vision on the initial visit. RESULTS: Eighty-two of
      the 361 patients (23%) had 20/40 or better acuity in at least one eye, 64 (18%)
      20/50 to 20/100, and 199 (55%) 20/200 to 20/400, whereas 16 (4%) had worse than
      20/400 in each eye at their most recent visit. In the patients with visual acuity
      of 20/40 or better, 59 (72%) had foveal sparing visible on ophthalmoscopic
      examination. The median time to develop visual acuity of 20/200 or worse was 22
      years for the patients with 20/40 or better visual acuity at their initial visit.
      Those seen initially in the first two decades of life with this level of acuity
      showed a median time of 7 years to reach a visual acuity of 20/200 or worse
      compared with 22 years and 29 years for those who were initially seen at ages 21
      to 40 or 41 to 60, respectively. Analyzing by the four 20-year age groups, the
      log rank statistic indicated significant differences in the survival experience
      among the four groups (P = 0.004). The median time to develop 20/200 vision or
      worse was 6 years for the patients with 20/50 to 20/100 visual acuity at their
      initial visit, and this result, based on the log rank statistic, was independent
      of age group at initial visit (P = 0.852). CONCLUSIONS: In a large cohort of
      Stargardt patients, a cross-sectional analysis showed that almost a quarter had
      vision of 20/40 or better, whereas 4% had acuity of worse than 20/400. The
      presence of foveal sparing ophthalmoscopically was associated with a higher
      prevalence of 20/40 or better visual acuity. Survival analysis showed that the
      prognosis of patients who initially were seen with visual acuity of 20/40 or
      better is related to age at initial visit.

PMID- 12799241
TI  - Variability of full-field electroretinogram responses in subjects without diffuse
      photoreceptor cell disease.
AB  - PURPOSE: To evaluate test-retest variability in electroretinogram (ERG) responses
      in subjects without evidence of diffuse photoreceptor cell disease. DESIGN:
      Cohort study. PARTICIPANTS: Forty subjects without diffuse photoreceptor cell
      disease. METHODS: Serial ERGs were performed on 40 subjects (mean age at the time
      of first ERG: 54 years; range: 38-75 years) over a period of 2 to 6 years. These
      subjects participated in a study by a pharmaceutical company investigating the
      effects of certain drugs, used for gastrointestinal disorders, on retinal
      function. None of the subjects showed any evidence of progressive change in
      retinal function related to the medications. The ERG responses that were
      evaluated included amplitudes and implicit times for the dark-adapted rod
      isolated and rod-dominant responses, light-adapted single flash response, and
      both light- and dark-adapted 31-Hz flicker responses. MAIN OUTCOME MEASURES: The
      data were analyzed by using analysis of variance methods, and a threshold
      criteria for significant change with 95% confidence was calculated for implicit
      times and an increase or decrease in ERG amplitudes. RESULTS: The threshold for
      significant change varied depending on the ERG stimulus. For the dark-adapted
      stimuli, a significant decrease in amplitude varied from 35% to 42% as compared
      with a variation of 53% to 73% for a significant increase. For the light-adapted
      stimuli, a significant decrease in amplitude varied by 52% as compared with a
      variation of 109% to 110% for a significant increase. The threshold for
      significant change for implicit times varied from 3.0 milliseconds to 8.7
      milliseconds. CONCLUSIONS: The measured test-retest variability in ERG amplitudes
      and implicit times in subjects without diffuse photoreceptor cell disease
      underscores the importance of conducting similar comprehensive studies of
      variability in patients with acquired and hereditary retinal diseases. These data
      are also of value for monitoring disease progression and in future therapeutic
      trials.

PMID- 12799242
TI  - Vitreoretinal surgery for cystoid macular edema associated with retinitis
      pigmentosa.
AB  - PURPOSE: To evaluate the anatomic and functional outcome of vitreoretinal surgery
      in eyes with retinitis pigmentosa (RP) and macular edema. DESIGN: Prospective
      noncomparative case series. PARTICIPANTS: Twelve consecutive eyes of eight
      patients with RP and a documented decrease in visual acuity (VA) to 20/60 or
      worse caused by macular edema refractory to medical therapy. METHODS: Pars plana
      vitrectomy was performed in the 12 eyes, followed by posterior hyaloid
      dissection, removal of the posterior inner limiting membrane after staining with
      indocyanine green, and gas tamponade. Preoperative best-corrected VAs ranged from
      20/60 to 20/400 (mean, 20/115). MAIN OUTCOME MEASURES: Changes in VA and foveal
      thickness as determined by optical coherence tomography (OCT). RESULTS: The mean
      preoperative retinal thickness at the fovea was 477 micro m. Optical coherence
      tomography showed a decrease in macular thickness of >40% in 10 eyes (83.3%),
      with a mean postoperative foveal thickness of 260 micro m. The mean VA increased
      from 20/115 to 20/45, with an average of three lines of improvement. CONCLUSIONS:
      Our results suggest that vitreoretinal surgery may effectively manage macular
      edema in RP.

PMID- 12799243
TI  - Comparison of silicone oil versus gas tamponade in the treatment of idiopathic
      full-thickness macular hole.
AB  - PURPOSE: To compare anatomic and functional outcomes of macular hole surgery with
      either silicone oil or C(3)F(8) gas tamponade. DESIGN: Retrospective comparative
      interventional study. PARTICIPANTS: Fifty-four eyes of 51 patients underwent pars
      plana vitrectomy for macular holes. Thirty-one eyes were treated with silicone
      oil tamponade, and 23 eyes were treated with C(3)F(8) tamponade. METHODS:
      Demographics, preoperative and postoperative characteristics, and complications
      were analyzed. MAIN OUTCOME MEASURES: Preoperative and postoperative visual
      acuity, initial hole closure, number of persistent or recurrent holes, number of
      reoperations, and final hole closure. RESULTS: The silicone oil and gas tamponade
      groups were demographically similar. The rate of hole closure after one operation
      with oil tamponade was significantly lower than that with gas tamponade (65% vs.
      91%; P = 0.022). The percentage of patients undergoing a second operation was
      significantly higher in the oil group (35% vs. 4%; P = 0.006). However, with
      reoperations, the final rate of hole closure was similar between the oil and gas
      groups (90% vs. 96%; P = 0.628). The final median visual acuity for the gas group
      was significantly better than for the oil group (20/50 vs. 20/70; P = 0.047).
      CONCLUSIONS: C(3)F(8) gas proved to be a more effective tamponade than silicone
      oil with respect to achieving initial closure of macular holes. Eyes receiving an
      oil tamponade required significantly more reoperations to achieve a similar rate
      of hole closure compared with eyes undergoing a gas tamponade. Final visual
      acuity was better for gas-operated eyes than for silicone-operated eyes.

PMID- 12799244
TI  - Prophylactic 360 degrees cryotherapy in fellow eyes of patients with spontaneous
      giant retinal tears.
AB  - PURPOSE: To assess the effect of prophylactic 360 degrees peripheral retinal
      cryotherapy in fellow eyes of patients with spontaneous giant retinal tears
      (GRTs) on the incidence of retinal detachment. DESIGN: Retrospective,
      noncomparative case series. PARTICIPANTS: Forty-eight consecutive patients (31
      male, 17 female) with spontaneous GRTs were included. The average age was 41 +/-
      2 years. The average refraction of the fellow eye was -4.0 +/- 0.8 diopters (D).
      INTERVENTION: Patients underwent vitrectomy and silicone oil tamponade in the
      affected eye and 360 degrees peripheral cryotherapy in the unaffected fellow eye
      during the same anesthetic. MAIN OUTCOME MEASURE: Attachment of the retina in the
      fellow eye was determined clinically by indirect ophthalmoscopy. RESULTS: During
      a mean follow-up of 84 +/- 10 months after cryotherapy, one patient (2%)
      experienced a retinal tear without retinal detachment, and three patients (6%)
      experienced a retinal detachment in the fellow eye. These occurred 18 +/- 9
      months after prophylactic treatment and were the result of a small retinal break
      in two cases and a GRT posterior to the treated area in one case. CONCLUSIONS:
      Prophylaxis of fellow eyes with 360 degrees cryotherapy appears to be associated
      with a lower incidence of retinal detachment than that reported in natural
      history studies. A prospective, randomized clinical trial of such prophylaxis is
      desirable but would require a sample size of at least 645 patients in each arm of
      the study, as well as long-term follow-up of at least 5 years to show an
      unequivocal difference in outcome.

PMID- 12799245
TI  - Acute macular pucker.
AB  - PURPOSE: To describe the presenting features, histopathology, and surgical
      outcome in a group of patients with rapidly progressive macular pucker. DESIGN:
      Retrospective interventional noncomparative case series. PARTICIPANTS: Five
      patients. METHODS: Review of case notes and the existing literature. RESULTS: All
      five patients had rapidly progressive visual loss and metamorphopsia over 2 weeks
      to 3 months, secondary to macular pucker after retinal tears or detachment.
      Vitrectomy and epiretinal membrane removal was performed within 1 month of
      diagnosis. In the absence of complications, there was rapid recovery of the
      visual acuity with resolution of metamorphopsia within 6 weeks to 3 months.
      Surgical complications limited the visual outcome in two cases. Histopathologic
      examination of epiretinal membrane removed from two of the cases suggests that
      these tend to form tubuloacinar structures and contain more retinal pigment
      epithelium-derived cells than tissue excised from cases with idiopathic macular
      pucker. CONCLUSIONS: Patients with acute macular pucker have precipitous visual
      loss caused by epiretinal membrane formation after retinal tear or detachment.
      Early surgery in these patients results in rapid recovery of visual acuity and
      resolution of metamorphopsia. The clinical features and comparative
      immunohistochemistry suggest that acute macular pucker is a distinct
      clinicopathologic entity.

PMID- 12799246
TI  - Risk factors for hypotony maculopathy.
AB  - PURPOSE: To determine the risk factors for hypotony maculopathy. DESIGN:
      Retrospective case control study. PARTICIPANTS: Two hundred twenty-eight eyes of
      228 patients with hypotony from one medical center. METHODS: Chart review of
      patients with hypotony from January 1988 to April 2001. Hypotony was defined as
      intraocular pressure of 5 mmHg or less. Cases of hypotony maculopathy had retinal
      or choroidal folds or both within the arcades. Controls had hypotony alone. Risk
      factors were evaluated using multiple logistic regression analysis. MAIN OUTCOME
      MEASURES: Risk factors for hypotony maculopathy, including age, gender, race,
      refractive error, systemic illness, intraocular pressure, primary filtering
      surgery, use of antifibrotic agents, and presence of choroidal effusion. RESULTS:
      Eighty-one case eyes with hypotony maculopathy and 147 control eyes with hypotony
      alone were identified. The mean age of patients with hypotony maculopathy was
      50.5 years +/- 18.7 compared with 70.6 years +/- 12.7 for the control patients (P
      < 0.001). More patients with hypotony maculopathy were male, 54.3% (44 of 81),
      than controls, 33.6% (49 of 147) (P = 0.004). The refractive error was -3.02 +/-
      3.67 diopters (D) for phakic eyes with hypotony maculopathy (n = 31), whereas the
      phakic control eyes' (n = 30) refractive error was -0.61 D +/- 2.00 (P = 0.003).
      Choroidal effusion was found in 21% (17 of 81) of the case eyes at diagnosis and
      52.4% (77 of 147) of the control eyes (P < 0.001). Race distribution and use of
      antifibrotics was similar for both groups. In multivariate analyses, young age,
      male gender, no history of diabetes, and absence of choroidal effusion predicted
      the development of hypotony maculopathy; in phakic eyes myopia was also a risk
      factor for hypotony maculopathy. CONCLUSIONS: Young age, male gender, and myopia
      are significant risk factors for hypotony maculopathy. A history of diabetes and
      the presence of choroidal effusion are associated with a decreased risk for
      hypotony maculopathy.

PMID- 12799247
TI  - Selective occlusion of subfoveal choroidal neovascularization in angioid streaks
      by using a new technique of ingrowth site treatment.
AB  - PURPOSE: To evaluate the visual and angiographic effects, as well as optical
      coherence tomography (OCT) findings, after a new treatment-neovascular ingrowth
      site photothrombosis-in patients with subfoveal choroidal neovascularization
      (CNV) secondary to angioid streaks. DESIGN: Prospective noncomparative small case
      series. PARTICIPANTS: Five eyes of 5 patients with angioid streaks in whom
      fluorescein and conventional indocyanine green (ICG) angiography clearly
      demonstrated distinct CNV vessels supplying the subfoveal neovascular complex.
      INTERVENTION: All five eyes were submitted to ICG-mediated photothrombosis of the
      neovascular ingrowth site. This novel, laser/dye-mediated technique uses large
      spot, lower-intensity 810-nm light for continuous application of laser energy to
      ICG concentrated in vascular lesions. MAIN OUTCOME MEASURES: Visual outcome and
      the results of fluorescein angiography, ICG angiography, and OCT evaluation.
      RESULTS: Fluorescein and conventional ICG angiography were sufficient to identify
      the CNV ingrowth site, which was juxtafoveal in 2 and extrafoveal in 3 of the 5
      eyes in this series. Obliteration of the entire neovascular lesion was achieved
      in all patients within the first hour after ICG-mediated photothrombosis of the
      CNV ingrowth site. At 1 week, the mean change in best-corrected visual acuity
      from baseline was +3.2 (+/-1.4) lines. Twelve months after treatment, visual
      acuity improved by 3 or more lines in all patients, and decreased leakage of
      fluorescein from the CNV, as well as OCT evidence of reduced or resolved retinal
      edema, was seen at the last follow-up visit. Major complications, such as
      immediate severe visual loss and retinal vessel occlusion in the early
      posttreatment period, were not identified in the 5 patients submitted to the
      procedure. CONCLUSIONS: Photothrombosis of the CNV ingrowth site by using lower
      intensity light to direct laser energy continuously after IV ICG infusion is a
      safe and effective technique for rapid induction of CNV hypoperfusion in selected
      patients and is associated with considerable improvement in visual acuity and
      partial restoration of the retinal architecture up to 12 months after treatment.

PMID- 12799248
TI  - Visual deterioration in giant cell arteritis patients while on high doses of
      corticosteroid therapy.
AB  - PURPOSE: To report the incidence and extent of visual deterioration in patients
      with giant cell arteritis (GCA) on high doses of systemic corticosteroids during
      the early stages of treatment; the various factors that may influence the
      outcome; and whether intravenous megadose corticosteroid therapy is more
      effective than oral therapy. DESIGN: Noncomparative interventional case series.
      PARTICIPANTS: One hundred forty-four patients with GCA (271 eyes) seen initially
      with visual loss (91 patients) and without visual loss (53 patients). All
      patients had biopsy-confirmed GCA and were followed while on high doses of
      systemic corticosteroid therapy for at least 2 weeks. METHODS: Every patient at
      the initial visit had an ophthalmic evaluation, including visual acuity, visual
      fields, intraocular pressure, slit-lamp and ophthalmoscopic evaluation,
      erythrocyte sedimentation rate (ESR; Westergren) and C-reactive protein (CRP)
      estimation, and temporal artery biopsy as soon as possible. If GCA was either
      strongly suspected or confirmed by biopsy, they were immediately started in our
      clinic on high doses of oral (80-120 mg) prednisone daily or intravenous megadose
      systemic corticosteroids (usually 150 mg dexamethasone sodium phosphate every 8
      hours for 1-3 days) followed by oral prednisone. At each visit they underwent all
      the initial ophthalmic evaluations and had an ESR and CRP evaluation done.
      Tapering of steroid therapy was not started until both ESR and CRP had reached
      their lowest stable levels. These showed marked interindividual variation and
      usually took approximately 2 weeks to stabilize. Then the steroid therapy was
      gradually tapered, guided primarily by the levels of ESR and CRP. No
      generalization is possible regarding the period required to achieve the
      maintenance dosage, because this also varied markedly from patient to patient.
      MAIN OUTCOME MEASURES: Visual acuity deterioration. RESULTS: While on high doses
      of steroid therapy during the initial stages of the treatment, only 9 (11 eyes)
      of the 91 patients seen initially with visual loss developed further visual
      acuity deterioration in one or both eyes within 5 days after the start of therapy
      (one of the eyes had normal vision initially), but none of the 53 patients
      initially seen without visual loss developed any visual deterioration. Six of the
      48 patients (13%) who were on intravenous steroid therapy had visual
      deterioration compared with 3 of 97 patients (3%) who were only on oral steroid
      therapy (P = 0.060). CONCLUSIONS: Our study shows that although a few eyes can
      develop visual deterioration while on high doses of steroid therapy, early,
      adequate steroid therapy is effective in preventing further visual loss in most.
      When further visual deterioration occurred despite high doses of systemic
      corticosteroids, it almost invariably started within 5 days after the start of
      the high-dose steroid therapy. There was no evidence that intravenous megadose
      steroid therapy was more effective than oral therapy in preventing visual
      deterioration.

PMID- 12799249
TI  - Posterior ischemic optic neuropathy after hemodialysis.
AB  - PURPOSE: To report a case of visual loss from posterior ischemic optic neuropathy
      (PION) after hemodialysis. DESIGN: Observational case report. METHODS: Neuro
      ophthalmic examination, neuro-imaging including computed tomography (CT) scan,
      magnetic resonance imaging (MRI) of the head and orbits, and magnetic resonance
      angiography (MRA) of the neck and cerebral vasculature, as well as
      electrophysiologic testing including electroretinogram (ERG) and visually evoked
      response (VER) were performed. RESULTS: Acute onset of painless bilateral no
      light perception vision with absent pupillary response to light and normal
      funduscopic examination occurred shortly after completion of hemodialysis.
      Computed tomography scan and MRA results were normal. Magnetic resonance imaging
      scan showed small vessel ischemic white matter changes. Electroretinogram results
      were normal and the VER was unrecordable. CONCLUSIONS: Visual loss after
      hemodialysis is a rare complication and is associated with anemia and hypotensive
      events. The visual loss is usually a result of anterior ischemic optic
      neuropathy. We were unable to find another instance in the literature of visual
      loss after hemodialysis resulting from PION.

PMID- 12799250
TI  - Magnetic resonance imaging of the functional anatomy of the inferior oblique
      muscle in superior oblique palsy.
AB  - PURPOSE: To study size and contractility of the normal inferior oblique (IO)
      muscle using high-resolution magnetic resonance imaging (MRI) and to evaluate
      abnormalities of the superior oblique (SO) and IO muscles in chronic SO palsy.
      DESIGN: Prospective, case control study. PARTICIPANTS: Thirteen patients with SO
      palsy and 17 orthotropic subjects. METHODS: High-resolution, surface coil MRI was
      used to obtain sets of contiguous, 2-mm thick coronal and sagittal images
      repeated in multiple gaze directions. Digital image analysis was used to measure
      IO and SO muscle cross-sectional areas for evaluation of size and contractility.
      Diagnosis of SO palsy in one bilateral and 12 unilateral cases was based on
      subnormal contractility and SO size less than the normal 95% confidence limit.
      Ipsilesional and contralesional oblique muscles were compared with controls and
      correlated with clinical characteristics. RESULTS: In all subjects, anterior
      movement and contractile thickening of the IO were observed in supraduction, with
      posterior movement and relaxational thinning in infraduction. The mean (+/-
      standard deviation) cross-sectional area of 15 normal control IO muscles was 13.4
      +/- 3.9 mm(2), with mean contractile increase from infraduction to supraduction
      of 5.7 +/- 2.6 mm(2). Subjects with SO palsy had incomitant hypertropia with a
      wide range of overelevation and underelevation in adduction (i.e., upshoot,
      downshoot). SO atrophy correlated with underdepression in adduction (P < 0.0001).
      Contralesional SO cross-section was slightly greater than normal (P = 0.004). The
      IO cross-section ipsilesional and contralesional to SO palsy did not, however,
      differ significantly from normal and did not correlate with elevation in
      adduction (P > 0.2). CONCLUSIONS: Quantitative morphometry by MRI can demonstrate
      IO size and contractility. Even in cases of unequivocal SO palsy associated with
      ipsilesional SO atrophy and deficient contractility, the degree of elevation in
      adduction was not correlated with IO size. This finding suggests that the
      associated overelevation in adduction, commonly termed "inferior oblique
      overaction," actually arises from some other mechanism than IO hypertrophy or
      excess contractility. Revision of clinical terminology seems warranted.

PMID- 12799252
TI  - Management of strabismus in nanophthalmic patients: a long-term follow-up report.
AB  - PURPOSE: The purpose of this study is to identify the characteristics of
      strabismus that coexist with nanophthalmos and to report the results of
      strabismus surgery performed on these small eyes. DESIGN: Retrospective,
      consecutive, noncomparative interventional case series. PARTICIPANTS: Fifteen
      bilateral nanophthalmic patients, of whom five underwent horizontal muscle
      surgery, were included in this study. METHODS: Chart review. The clinical
      examination included visual acuity assessments using the linear Snellen and the
      Lea charts, slit-lamp and fundus examinations, intraocular pressure, and axial
      length measurements. The orthoptic examination consisted of measurements of
      ocular deviations using the prism cover test with an accommodative target at both
      near and distance with and without refractive correction, assessment of ocular
      motility with ductions and versions, binocularity with Worth's four-dot test, and
      the Titmus test. Amblyopia was treated with part-time occlusion. Surgery for the
      correction of esotropia included bilateral medial rectus recessions or recess
      resect procedures. MAIN OUTCOME MEASURES: Magnitude of strabismic deviation, best
      corrected visual acuity, and the level of binocular vision achieved were
      monitored. RESULTS: The average age of enrollment in the study was 4.7 (range, 1
      12) years. The patients were followed for an average of 7.0 (range, 4-14) years.
      The mean axial length was determined as 18.4 mm (range, 15.5-20.7). The mean
      refractive error in spherical equivalents was measured as +9.9 and ranged between
      +4.0 and +15.0 diopters. Five patients (33%) had nonaccommodative esotropia, four
      (27%) had partially refractive esotropia, four (27%) had microesotropia, and two
      (13%) had exotropia. Five patients, all having nonaccommodative esotropia,
      underwent surgery for the correction of ocular misalignment. Diminishing the
      surgical dose in these small eyes resulted in undercorrections. Despite patching,
      3 patients (20%) had unilateral and 12 patients (80%) had bilateral amblyopia at
      the conclusion of the study. CONCLUSIONS: Strabismus in nanophthalmos usually
      manifests as nonaccommodative and partially refractive esotropia. Medial rectus
      recession should be applied with care to prevent adduction deficit and
      convergence insufficiency. Otherwise, there seems to be no need for decreasing
      the surgical dose with regard to the smaller axial length. Amblyopia tends to be
      persistent in these patients.

PMID- 12799253
TI  - Treatment of metastatic retinoblastoma.
AB  - PURPOSE: The risk for death in patients with retinoblastoma is increased in those
      who present with metastatic disease, and the role of intensive chemotherapy and
      autologous hematopoietic stem cell rescue in these patients remains unclear.
      DESIGN: Nonrandomized interventional case series. PARTICIPANTS: Four consecutive
      patients with metastatic retinoblastoma. METHODS: We treated four patients with
      retinoblastoma metastatic to the bone and bone marrow with intensive
      chemotherapy, consolidation with megatherapy, and autologous hematopoietic stem
      cell rescue. Chemotherapy included courses of carboplatin and etoposide
      alternating with cyclophosphamide, etoposide, and either carboplatin or
      cisplatin. Radiation therapy was delivered to areas of bone metastases. MAIN
      OUTCOME MEASURES: Patient survival. RESULTS: All patients completed and responded
      to the scheduled therapy; complete response of the bone marrow disease was
      documented after two courses of chemotherapy in all cases. Two patients are long
      term survivors. CONCLUSIONS: The treatment described has been successful in
      obtaining disease-free survival in patients with metastatic retinoblastoma.

PMID- 12799254
TI  - Intrathecal chemotherapy for recurrent central nervous system intraocular
      lymphoma.
AB  - PURPOSE: To report the use of intrathecal chemotherapy for two patients with
      recurrent central nervous system (CNS) intraocular lymphoma. DESIGN: Two
      interventional case reports. PARTICIPANTS: The clinical course of two patients
      with documented recurrent CNS intraocular lymphoma were retrospectively reviewed.
      INTERVENTION: Both patients had previously undergone external beam radiation
      therapy to the orbit and brain, as well as systemic methotrexate (MTX) and
      intrathecal cytarabine (Ara-C), for primary CNS intraocular lymphoma. Both
      patients developed recurrent CNS intraocular lymphoma and treatment involved
      intrathecal MTX and Ara-C delivered by means of an Ommaya reservoir. MAIN OUTCOME
      MEASURE: Survival and resolution of intraocular lymphoma. RESULTS: Complete
      remission of the CNS intraocular lymphoma was seen in both patients. Both
      patients maintain reading visual acuity in at least one eye. Both patients remain
      disease free with lymphoma in remission for greater than 5 years after initial
      diagnosis. CONCLUSIONS: Intrathecal chemotherapy for recurrent CNS intraocular
      lymphoma seems to be effective in preserving vision and possibly increasing
      survival.

PMID- 12799255
TI  - Ocular adnexal lymphoid proliferations: clinical, histologic, flow cytometric,
      and molecular analysis of forty-three cases.
AB  - PURPOSE: To describe the clinical features, histologic findings, flow cytometric
      immunophenotypes, and molecular profiles of ocular adnexal lymphoid
      proliferations. STUDY DESIGN: Prospective noncomparative case series.
      PARTICIPANTS: Forty-three patients suspected of having ocular adnexal lymphoid
      proliferations were biopsied and prospectively evaluated. METHODS: Provisional
      diagnoses were made on the basis of routine histology and immunohistochemistry
      for B and T cells. Results of flow cytometric immunophenotyping (FCI) and
      molecular assessment using polymerase chain reaction for immunoglobulin heavy
      chain (IgH) and TCR gamma chain gene rearrangement and bcl-2/IgH translocation
      were then incorporated into a final diagnosis. Demographic and clinical outcome
      data were collected. MAIN OUTCOME MEASURES: Final diagnosis based on histology,
      flow cytometry, and polymerase chain reaction. RESULTS: Forty-three cases were
      studied. Final diagnoses included 17 lymphomas, 18 chronic inflammations, 4
      reactive lymphoid hyperplasias, and 4 atypical lymphoid infiltrates. Preliminary
      evaluation accurately categorized all 43 cases as either lymphoma or nonlymphoma.
      FCI permitted more precise subclassification of the lymphomas according to the
      Revised European American Lymphoma (REAL) system of nomenclature as follows:
      eight marginal zone B cell (mucosa-associated lymphoid tissue type), three mantle
      cell, two follicular, three large cell, and one lymphoplasmacytoid lymphoma. FCI
      showed a clonal B cell proliferation in 94% (16 of 17) of the lymphomas; FCI
      identified a clonal B cell population in 4% (1 of 25) of cases of nonlymphomas.
      Molecular evidence of clonality was identified in 88% (15 of 17) of lymphomas,
      39% (7 of 18) of chronic inflammations, and 50% (4 of 8) of reactive lymphoid
      hyperplasias and atypical lymphoid infiltrates. CONCLUSIONS: The histologic
      diagnosis of ocular adnexal lymphoid lesions is highly accurate when determined
      by an experienced pathologist. FCI refines the histologic diagnosis and
      classification. Results of molecular studies should be interpreted in conjunction
      with clinical, histologic, and immunophenotyping findings.

PMID- 12799256
TI  - SubTenon's infusion of steroids for treatment of orbital hemangiomas.
AB  - PURPOSE: To introduce an alternate technique for the treatment of infantile
      orbital hemangiomas. DESIGN: Non-comparative case series. PARTICIPANTS: Seven
      consecutive children with orbital hemangiomas. INTERVENTION: Posterior subTenon's
      steroid infusion using a blunt-tip cannula. MAIN OUTCOME MEASURES: Clinical
      stabilization, improvement, or resolution. RESULTS: Significant and sustained
      involution of the hemangiomas occurred in all cases. No local or systemic
      complications occurred. CONCLUSIONS: The results of subTenon's steroid infusion
      for the treatment of orbital hemangiomas in children are encouraging and may be
      associated with fewer intraoperative risks compared with direct intralesional
      injection.

PMID- 12799258
TI  - Successful treatment with 5-Fu.

PMID- 12799259
TI  - Perinatal visual loss.

PMID- 12799261
TI  - Economic evaluation of photodynamic therapy with verteporfin.

PMID- 12799263
TI  - Implicit case review.

PMID- 12799264
TI  - Wieger's ligament.

PMID- 12799267
TI  - Alternative medicine for glaucoma.

PMID- 12799268
TI  - Preservation of anterior capsule.

PMID- 12799272
TI  - Intraorbital foreign bodies.

PMID- 12799271
TI  - Intraocular inflammation after cataract surgery.

PMID- 12799273
TI  - Progress in glaucoma: early detection, new treatments, less blindness.

PMID- 12799274
TI  - The association of cardiovascular disease with the long-term incidence of age
      related maculopathy: the Beaver Dam Eye Study.
AB  - PURPOSE: To examine the association between cardiovascular disease and its risk
      factors and the 10-year incidence of age-related maculopathy. DESIGN: Population
      based cohort study. PARTICIPANTS: Persons 43 to 86 years of age at baseline
      examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 3684
      persons participated in a 5-year follow-up examination and 2764 participated in a
      10-year follow-up examination. METHODS: Standardized protocols for physical
      examination, blood collection, administration of a questionnaire, and
      stereoscopic color fundus photography to determine age-related maculopathy. The
      Kaplan-Meier (product-limit) survival approach and discrete linear logistic
      regression were used in the data analysis. MAIN OUTCOME MEASURES: Incidence and
      progression of age-related maculopathy. RESULTS: When age, gender, and history of
      heavy drinking, smoking, and vitamin use were controlled for, higher systolic
      blood pressure at baseline was associated with the 10-year incidence of retinal
      pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood
      pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative
      macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse
      pressure at baseline was associated with the incidence of retinal pigment
      epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001),
      increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative
      macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of
      age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum
      high-density lipoprotein cholesterol at baseline was associated with pure
      geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29;
      95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with
      the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a
      week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04)
      exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and
      progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05).
      Neither a history of stroke nor heart attack was associated with the incidence or
      progression of age-related maculopathy. CONCLUSIONS: These findings indicate
      relationships between higher pulse pressure (a presumed indicator of age-related
      elastin and collagen changes in Bruch's membrane) and systolic blood pressure
      with an increased 10-year incidence of some lesions defining early age-related
      maculopathy and exudative macular degeneration.

PMID- 12799275
TI  - Hematopoietic stem cells 2002: genetics and function. Proceedings of the Fourth
      International Symposium. Tubingen, Germany. September 19-21, 2002.

PMID- 12799276
TI  - New models to investigate mechanisms of disease genesis from primitive BCR-ABL(+)
      hematopoietic cells.
AB  - Three years ago we described a novel autocrine IL-3/G-CSF mechanism active in the
      leukemic CD34(+) cells from chronic myeloid leukemia (CML) patients in chronic
      phase (PNAS 96: 12804-12809, [1999]). We also showed that exposure of the most
      primitive CD34(+) cells from normal human bone marrow to excess IL-3 stimulates
      not only the division of these cells but also their differentiation. In contrast,
      both IL-3 and G-CSF cause an expansion of the more mature types of normal CD34(+)
      progenitors. These findings suggested that the autocrine IL-3/G-CSF mechanism
      active in CML stem cells can compromise their self-renewal in spite of increasing
      their proliferative activity, which, in turn, might explain the paradoxically
      slow rate of expansion of this compartment over time in patients with latent
      disease. To investigate this hypothesis, we have begun to characterize the
      numbers and types of cells generated from chronic phase CML patients' cells
      transplanted into adult immunodeficient mice or fetal sheep, and also from
      transplants of primitive murine and human hematopoietic cells transduced with a
      retroviral BCR-ABL vector. Our findings to date using these models reinforce the
      importance of the autocrine IL-3/G-CSF mechanism in the development of CML. BCR
      ABL appears to directly activate IL-3 and G-CSF production in primitive
      hematopoietic cells and this is important to their transplantable leukemogenic
      activity. However, the development in vivo of an overt leukemia from primitive
      BCR-ABL(+) hematopoietic cells can be very delayed. These models thus offer new
      opportunities for analyzing the molecular events that underlie the pathogenesis
      of human CML and the future testing of new therapeutic approaches.

PMID- 12799277
TI  - Identification, characterization, and function of a novel oncogene: the
      peripheral cannabinoid receptor Cb2.
AB  - By means of retroviral insertional mutagenesis, we identified a novel common
      virus integration site (cVIS) (Evi11) in murine leukemias, and demonstrated that
      Cb2, encoding the peripheral cannabinoid receptor, is the potential proto
      oncogene located in that region. Cb2 is a 7-transmembrane G protein-coupled
      receptor (GPCR), which is normally expressed on B lymphocytes. Using transwell
      assays we observed strong migration of Cb2-expressing cells upon stimulation with
      2-arachidonoylglycerol (2-AG), a potent endocannabinoid. Overexpression of Cb2
      receptor on murine myeloid precursor cells causes a block of neutrophilic
      differentiation, a major characteristic of myeloid leukemia. Intriguingly, we
      could not detect functional Cb2 receptors on normal murine bone marrow precursor
      cells. Furthermore, analysis of human acute myeloid leukemia (AML) samples
      revealed the presence of CB2 mRNA transcripts in several cases. Furthermore,
      migration could be induced by 2-AG when analyzed in one of the patient samples.
      Our data suggest that the initially identified cVIS, Evi11, encodes for a murine
      onco-protein and that human CB2 may be involved in certain cases of human AML as
      well.

PMID- 12799278
TI  - Thrombopoietin is essential for the maintenance of normal hematopoiesis in
      humans: development of aplastic anemia in patients with congenital
      amegakaryocytic thrombocytopenia.
AB  - Recently, we and others could define the molecular cause of the rare disease
      congenital amegakaryocytic thrombocytopenia (CAMT) as mutations in the c-mpl gene
      (Blood 97: 139, 2001). We proposed that c-mpl mutations are the cause not only
      for the hypomegakaryocytic thrombocytopenia, but also for the development of an
      aplastic anemia (AA) in patients with CAMT. The effects of thrombopoietin (TPO)
      on early multipotent hematopoietic progenitors were elucidated by a recent series
      of in vitro and in vivo studies. Like CAMT patients, mice lacking the TPO
      receptor c-Mpl demonstrate a major reduction of early hematopoietic progenitor
      cells of all lineages. However, these mice achieve a normal marrow cellularity
      and composition, despite the lack of megakaryocytes. On the other hand, the
      incidence of development of aplastic anemia in CAMT is not clear owing to
      difficult and not consistent diagnosis of this disease.

PMID- 12799279
TI  - Normalization of previously shortened telomere length under treatment with
      imatinib argues against a preexisting telomere length deficit in normal
      hematopoietic stem cells from patients with chronic myeloid leukemia.
AB  - Telomeres are composed of TTAGGG repeats and associated proteins. In somatic
      cells, telomere repeats are lost with each cell division, eventually leading to
      genetic instability and cellular senescence. In previous studies, we described
      substantial and disease stage-specific telomere shortening in peripheral blood
      (PB) leukocytes from patients with chronic myeloid leukemia (CML). Here, we
      sought to determine whether age-adjusted telomere length in PB granulocytes
      (deltaTEL(gran)) is associated with response to treatment with the selective
      tyrosine kinase inhibitor imatinib. A total of 517 samples from 206 patients in
      chronic phase (CP), accelerated phase (AP), and blast crisis (BC) before and up
      to 706 days after initiation of imatinib therapy (median: 144 days) were analyzed
      by quantitative fluorescence in situ hybridization of interphase cells in
      suspension (Flow-FISH); telomere fluorescence was expressed in molecular
      equivalents of soluble fluorochrome units (MESF). Telomere length in samples from
      start of treatment up to day 144 was significantly shorter (mean +/- SE; -1.5 +/-
      0.3 kMESF) compared to samples from patients treated for more than 144 days (-0.8
      +/- 0.3 kMESF, p = 0.035). In patients with repeated measurements, a significant
      increase in telomere length under treatment was observed. Median telomere length
      in major remission was found to be significantly longer compared to patients
      without response to treatment measured either by cytogenetics (n = 246, p <
      0.05), interphase FISH (n = 204, p = 0.002), or quantitative RT-PCR (n = 371, p <
      0.05). In conclusion, the increase in telomere length under treatment with
      imatinib reflects a shift from Ph+ to Ph- cells in the PB of patients with CML.

PMID- 12799280
TI  - Thrombopoietin: accumulating evidence for an important biological effect on the
      hematopoietic stem cell.
AB  - Although it is clear that thrombopoietin is the primary regulator of
      thrombopoiesis, several lines of evidence indicate that the hormone affects
      multiple aspects of hematopoiesis: the in vivo administration of TPO increases
      marrow levels of erythroid, myeloid, and megakaryocytic progenitor cells and its
      genetic elimination or that of its receptor (c-mpl) reduces the numbers of these
      cells; all hematopoietic stem cells (HSCs) are c-mpl+; genetic elimination of c
      mpl reduces the numbers of murine HSCs by 7-8-fold; and its null mutation in
      humans leads to congenital amegakaryocytic thrombocytopenia, a disorder that
      almost invariably leads to aplastic anemia. Recently, we have begun to explore
      the role of TPO in the HSC self-renewal and expansion that characterizes the post
      stem-cell-transplantation period. Using limiting dilution cell transplantation
      analyses, we found that HSC self-renewal and expansion is reduced 10-20-fold
      after transplantation of normal stem cells into tpo null mice compared to their
      wild-type counterparts. Although the molecular mechanisms responsible for these
      findings are only now being explored, it is expected that a greater understanding
      of the roles played by TPO in HSC physiology will lead to novel therapeutic
      opportunities.

PMID- 12799281
TI  - Telomeres in hematopoietic stem cells.
AB  - Hematopoietic stem cells have an impressive regenerative potential, strikingly
      illustrated in transplantation experiments using limited number of cells. In
      mice, serial transplantation experiments suggest that individual hematopoietic
      cells are capable of extensive self-renewal and that any possible limitations in
      the replicative potential of individual hematopoietic stem cells are not
      affecting normal blood cell formation. The situation with human hematopoietic
      stem cells is less clear. Unlike the situation in the mouse, the telomere length
      in nucleated human blood cells shows a remarkable decline with age. Furthermore,
      even partial telomerase deficiency in humans typically results in marrow failure,
      whereas complete lack of telomerase is tolerated up to several generations in the
      mouse. The decline in telomere length in human leukocytes with age follows a
      cubic function and is much higher in lymphocytes than in granulocytes. This
      finding suggests that, under normal circumstances, telomere loss is more likely
      to compromise the function of lymphocytes than the function of hematopoietic stem
      cells. To reconcile differences in telomere biology between man and mice, it has
      been proposed that telomere shortening evolved as a tumor suppressor mechanism in
      long-lived species that may not exist in shorter-lived mammals. According to this
      model, telomeres in human cells are intimately involved in signaling cell cycle
      progression and cell division. Most likely, a minimum number of telomere repeats
      is required at each telomere to prevent activation of a "telomere checkpoint" and
      allow cell cycle progression. Telomere length measurements appear useful to
      distinguish between depletion and exhaustion of hematopoietic stem cells as a
      cause of marrow failure.

PMID- 12799282
TI  - Angiogenic factors reconstitute hematopoiesis by recruiting stem cells from bone
      marrow microenvironment.
AB  - The mechanism by which angiogenic factors recruit bone marrow (BM)-derived
      quiescent endothelial and hematopoietic stem cells (HSCs) is not known. Here, we
      report that functional vascular endothelial growth factor receptor-1 (VEGFR1, Flt
      1) is expressed on a subpopulation of human CD34(+) and mouse Lin-Sca-1(+)c
      Kit(+) BM-repopulating stem cells, conveying signals for recruitment of HSCs and
      reconstitution of hematopoiesis. Inhibition of VEGFR1 signaling, but not VEGFR2
      (Flk-1, KDR), blocked HSC cell cycling, differentiation and hematopoietic
      recovery after BM suppression, resulting in the demise of the treated mice.
      Plasma elevation of placental growth factor (PlGF), which signals through VEGFR1,
      but not VEGFR2, restored hematopoiesis during the early and late phases following
      BM suppression. The mechanism whereby PlGF enhanced early phases of BM recovery
      was mediated directly through rapid chemotaxis of readily available VEGFR1(+) BM
      repopulating and progenitor cells. The late phase of hematopoietic recovery was
      driven by PlGF-induced upregulation of matrix metalloproteinase-9 (MMP-9) in the
      BM, mediating the release of soluble Kit-ligand (sKitL). sKitL increased
      proliferation and motility of HSCs and progenitor cells, thereby augmenting
      hematopoietic recovery. PlGF promotes recruitment of VEGFR1(+) HSCs from a
      quiescent to a proliferative microenvironment within the BM, favoring
      differentiation, mobilization, and reconstitution of hematopoiesis.

PMID- 12799284
TI  - Characterization of cord blood hematopoietic stem cells.
AB  - A major problem hampering the development of effective stem cell-based therapies
      is the absence of a clear understanding of the composition of the hematopoietic
      stem cell (HSC) pool in humans and how ex vivo manipulation can differentially
      affect the various HSC classes. This paper will review recent advances in the use
      of the NOD/SCID xenotransplant assay to characterize the human stem cell
      compartment and to determine how ex vivo culture affects stem cells. Using
      lentivector-mediated clonal tracking we found that only 4 days of culture can
      significantly reduce the number of SCID-repopulating cells (SRCs) contributing to
      the human graft. Similar results were seen with a competitive assay strategy
      where non-cultured cells marked with the RFP-lentivector markedly outcompete
      cultured cells marked with a EGFP-lentivector both transplanted into the same
      NOD/SCID mouse. A novel intrafemoral (IF) assay was developed to permit the
      transplantation of human stem cells that might be difficult to detect using the
      traditional IV injection method. With the IF assay we identified a novel class of
      human stem cell with the ability to rapidly generate a large graft of human
      myeloid and erythroid cells within 2 weeks post transplant.

PMID- 12799283
TI  - Nonpeptide mediators in the hematopoietic microenvironment.
AB  - Migration of hematopoietic stem and progenitor cells (HPCs) is controlled by
      chemotactic factors released in the hematopoietic microenvironment. In
      particular, the chemokine SDF-1, which activates the G protein-coupled receptor
      (GPR) CXCR4, plays an important role in progenitor cell mobilization and homing.
      However, we provide evidence that ligands of other GPRs similarly act on CD34(+)
      hematopoietic progenitors. These ligands comprise non-peptide mediators,
      including the cysteinyl-leukotriene receptor CysLT1, and stimulate migration and
      integrin-dependent adhesion of HPCs. Moreover, continuous activation of a GPR by
      a specific ligand upregulates the responsiveness of other GPRs to their
      corresponding ligands. These findings suggest that HPC migration may not depend
      on a single chemokine receptor (e.g., CXCR4). Rather, mobilization and homing of
      HPCs involve several GPRs, which interact with each other as well as with
      adhesion molecules. Pharmacological activation and inhibition of the GPR may
      allow HPC mobilization and homing to be modulated.

PMID- 12799285
TI  - Hematopoietic stem cell transplantation across major genetic barriers: tolerance
      induction by megadose CD34 cells and other veto cells.
AB  - Studies in mice and humans demonstrate that transplantation of hematopoietic
      progenitors in numbers larger than commonly used ("megadose" transplants)
      overcomes major genetic barriers. In vitro studies suggest that veto cells,
      within the population of hematopoietic progenitors, facilitate this favorable
      outcome. Thus, when purified CD34(+) cells were added to bulk mixed-lymphocyte
      reactions (MLRs) they suppressed CTLs against the donor's stimulators, but not
      against stimulators from a third party. This tolerizing activity depends on cell
      contact and can be blocked by the caspase inhibitor BD-FMK, suggesting that the
      effector host T cells are deleted by apoptosis upon interaction with the CD34(+)
      cells. Early myeloid CD33(+) cells generated by short-term ex vivo expansion of
      CD34(+) cells also exhibit veto activity, and these cells can be grown in large
      numbers. Tolerance induction can be further enhanced by other veto cells. Perhaps
      the most potent veto cell is the CD8+ CTL. However, this cell is also associated
      with marked GVHD (graft-versus-host disease. GVHD can be separated from the veto
      activity by generating anti-third party CTLs under IL2 deprivation. Under such
      selective pressure only the stimulated clones which make IL2 can survive, while
      anti-host clones die. In vivo studies show that such anti-third party veto CTLs
      can be used safely for tolerance induction without GVHD.

PMID- 12799286
TI  - Complement-fixing CD45 monoclonal antibodies to facilitate stem cell
      transplantation in mouse and man.
AB  - Broadening the applicability of stem cell therapies requires safer preparative
      regimens for patients. The CD45 antigen is present on all cells of the
      hematopoietic lineage, and using a murine model, we determined whether a lytic
      CD45 monoclonal antibody could produce persistent aplasia and whether it could
      facilitate syngeneic or allogeneic stem cell engraftment. After its systemic
      administration, we found that all leukocyte subsets in peripheral blood were
      markedly diminished, but only the effect on the lymphoid compartment was
      sustained and marrow progenitor cells were spared from destruction. Given the
      transient effects of the monoclonal antibody on myelopoiesis and the more
      persistent effects on lymphopoiesis, we asked whether this agent could contribute
      to donor hemopoietic engraftment after subablative transplantation. Treatment
      with anti-CD45 alone did not enhance syngeneic engraftment, consistent with its
      inability to destroy progenitor cells and permit competitive repopulation with
      syngeneic donor stem cells. By contrast, the combination of anti-CD45 and an
      otherwise inactive dose of total-body irradiation allowed engraftment of H2 fully
      allogeneic donor stem cells. We attribute this result to the recipient
      immunosuppression produced by depletion of CD45-positive lymphocytes. We next
      assessed a pair of unconjugated rat anti-human CD45 monoclonal antibodies (MAbs),
      YTH54.12 and YTH25.4, in a clinical trial in patients who were to receive stem
      cell transplantation for acute leukemia. The maximum tolerated dose of these
      MAbs, 400 microg/kg/day, produced a pattern of response identical to that seen in
      the mice, with marked reductions in circulating lymphoid and myeloid cells and
      sparing of early marrow progenitors. In two of three patients with active
      leukemia, the MAbs also produced a decrease in the percentage of leukemic blast
      cells in bone marrow. These pre-clinical and clinical results warrant further
      evaluation of anti-CD45 MAbs in subablative preparative regimens for stem cell
      transplantation.

PMID- 12799287
TI  - Differential gene expression underlying the functional distinctions of primary
      human CD34+ hematopoietic stem and progenitor cells from peripheral blood and
      bone marrow.
AB  - The restorative capacity of human CD34(+) hematopoietic cells is clinically used
      in the autologous and allogeneic transplant setting to support cytotoxic therapy.
      We examined gene expression patterns of highly enriched bone marrow CD34(+) (BM
      CD34(+)) or G-CSF-mobilized peripheral blood CD34(+) (PB-CD34(+)) cells by cDNA
      array technology, quantitative real-time RT-PCR, and flow cytometry, to identify
      molecular causes underlying the functional differences between circulating and
      sedentary hematopoietic stem and progenitor cells. The greater cell cycle and DNA
      synthesis activity of BM-CD34(+) compared to PB-CD34(+) cells was reflected by
      the 2- to 5-fold higher expression of 9 genes involved in cell cycle, 11 genes
      regulating DNA synthesis, and the cell cycle-initiating transcription factor E2F
      1. The 2- to 3-fold greater expression of 5 pro-apoptotic genes in PB-CD34(+)
      cells indicated a higher apoptotic activity, which could functionally be
      corroborated by apoptosis assays. Thrombin receptor (PAR1), known to play a role
      in trafficking of malignant cells, was 3.6-fold higher expressed in circulating
      CD34(+) cells than in BM-CD34(+) cells. Guidance via thrombin receptor might
      molecularly mediate stem cell migration. In summary, our study provides gene
      expression profiles of primary human CD34(+) hematopoietic cells of blood and
      marrow. Our data molecularly confirm and explain the finding that CD34(+) cells
      residing in the bone marrow are cycling more rapidly, whereas circulating CD34(+)
      cells consist of a higher number of quiescent stem and progenitor cells.
      Moreover, our data give novel molecular insights into stem cell migration and
      differentiation.

PMID- 12799288
TI  - Development of gene therapy for hemoglobin disorders.
AB  - The hemoglobin disorders, severe beta-thalassemia and sickle cell anemia, are
      prevalent monogenetic disorders which cause severe morbidity and mortality
      worldwide. Gene therapy approaches to these disorders envision stem cell targeted
      gene transfer, autologous transplantation of gene-corrected stem cells, and
      functional, phenotypically corrective globin gene expression in developing
      erythroid cells. Lentiviral vector systems potentially appear to afford
      adequately efficient gene transfer into stem cells and are capable, with
      appropriate genetic engineering, of transferring a globin gene with the
      regulatory elements required to achieve high-level, erythroid-specific
      expression. Herein are results obtained in use of lentiviral vectors to insert a
      gamma-globin gene into murine stem cells with phenotypic correction of the
      thalassemia phenotype. Further, we have developed a drug-selection system for
      genetically modified stem cells based on a mutant form of methylguanine,
      methyltransferase, which allows selective amplification of genetically modified
      stem cells with phenotypic correction even in the absence of myeloablation prior
      to stem cell transplantation. These advances provide essential preclinical data
      which build toward the development of effective gene therapy for the severe
      hemoglobin disorders.

PMID- 12799289
TI  - Efficient characterization of retro-, lenti-, and foamyvector-transduced cell
      populations by high-accuracy insertion site sequencing.
AB  - The identification of unknown genomic flanking DNA sequences can be used for the
      molecular monitoring of retro-, lenti- and foamyviral integration, transgenes in
      early embryogenesis, insertional mutagenesis, cell fate, and stem cell
      plasticity. Most existing methods reflect shortcomings in sensitivity and or
      specificity, thus limiting genomic sequencing of unknown flanking DNA to clonal
      preparations. The application of linear amplification-mediated PCR (LAM-PCR), a
      recently developed direct sequencing technique for flanking DNA, should
      circumvent current limitations in different research fields. This technique
      combines preamplification of target DNA with a unique succession of enzymatic
      reactions on solid-phase. Using LAM-PCR, we show the previously unfeasible in
      vivo retro-, lenti- and foamyvirus integration site analysis in primate
      peripheral blood hematopoietic cells and human xenograft hematopoiesis. In light
      of two severe adverse events that occurred in a clinical SCID-X1 gene therapy
      trial, in vivo monitoring of the reinfused transduced cell pool by integration
      site analysis will be an important component of each gene transfer and therapy
      study aimed at clinical use.

PMID- 12799290
TI  - From embryos to embryoid bodies: generating blood from embryonic stem cells.
AB  - Differentiation of embryonic stem (ES) cells in vitro yields abundant
      hematopoietic progenitors, but achieving stable hematopoietic engraftment of
      irradiated mice has proven difficult, begging the question of whether ES cells
      give rise to hematopoietic stem cells in vitro, and limiting the application of
      ES cells as experimental and therapeutic models. We have employed a number of
      hematopoietic regulatory genes to probe the nature and developmental potential of
      ES-derived blood precursors. The chronic myeloid leukemia-associated BCR/ABL
      oncoprotein transforms a novel class of ES-derived embryonic hematopoietic stem
      cell that represents a common progenitor of primitive erythropoiesis and
      definitive lymphoid-myeloid blood development. Expression of the homeobox gene
      HoxB4 generated normal, non-leukemic hematopoietic progenitors that enabled long
      term, multilineage hematopoietic engraftment in primary and secondary mouse
      recipients. We have used these repopulating hematopoietic stem cells to model
      therapeutic transplantation from ES cells. We treated an immunodeficient Rag2(-/
      ) mouse by therapeutic cloning, that is, isogenic ES cell generation by somatic
      cell nuclear transfer, gene correction, and cell replacement therapy. Comparable
      approaches with human ES cells are being developed to lay the foundation for
      cellular therapies in patients with a variety of bone marrow diseases.

PMID- 12799291
TI  - Hematopoietic stem cell emergence in the human embryo and fetus.
AB  - Two waves of hematopoietic stem cell generation take place in the first month of
      human gestation. The first one has long been known to occur in the yolk sac; only
      recently was another one identified that results in the development, from the
      27th day, of clusters of hematopoietic cells on the ventral endothelium of the
      aorta and vitelline artery. This latter, intra-embryonic phase of blood cell
      progenitor production is undoubtedly local since its presumptive territory of
      occurrence, the para-aortic splanchnopleura, is endowed with blood-forming
      potential in vitro from, at least, day 19 of development. The first multipotent,
      lympho-myeloid stem cells emerge within that intra-embryonic territory, whereas
      the yolk sac only produces myeloid precursor cells devoid of lymphoid potential.
      The forerunners of the hematopoietic stem cells born to intra-embryonic arteries
      appear to migrate from the splanchnopleura as KDR(+) angio-hematopoietic cells
      that colonize the ventral wall of the aorta to give rise to hematogenous
      endothelium. All these results indicate that stem cells for human definitive
      hematopoiesis emerge within the embryo, in the walls of truncal arteries, from
      splanchnopleural ancestors and through a vascular endothelial intermediate stage.
      Less expectedly, blood-forming endothelial cells were also encoutered in the
      embryonic and fetal liver and in the fetal and, even, adult bone marrow,
      suggesting that a filiation between vascular and hematopoietic cells may persist
      during the whole life.

PMID- 12799292
TI  - Biology and plasticity of CD133+ hematopoietic stem cells.
AB  - AC133 (CD133) is a highly conserved antigen expressed on hematopoietic stem cells
      with unknown function. In order to further characterize CD133(+) progenitor
      cells, we purified CD133(+) stem cells using the method of magnetic activated
      cell sorting (MACS) from healthy adult volunteers mobilized with granulocyte
      colony-stimulating growth factor (G-CSF) to a mean purity of 94%. The purified
      CD133(+) cells highly engrafted NOD/SCID mice. In addition, unseparated
      mononuclear cells or CD133(+) stem cells isolated from the bone marrow of
      transplanted NOD/SCID mice gave rise to engraftment of secondary recipients. Upon
      ex vivo culture of purified CD133(+) cells with FLT3/Flk2 ligand (FL) and
      interleukin-6 (IL-6), a plastic-adherent cell population could be observed after
      6 weeks in culture. These adherent cells did not express CD34 or CD133 antigens
      on their surface, nor did they express markers for endothelial, mesenchymal, or
      dendritic cells. After incubation of these adherent cells with stem cell factor
      (SCF), non-adherent cells were observed which partially co-expressed CD133, but
      were negative for CD34. These nonadherent CD34(-) cells showed a high engraftment
      capacity in NOD/SCID mice. From our results, we conclude that CD133 might be a
      marker of early progenitors with a high NOD/SCID engraftment potential. The fact
      that CD133(+) hematopoietic progenitors can give rise to an adherent population
      which is CD133(-) and CD34(-) and that these cells can again give rise to a
      CD133(+)CD34(-) stem cell population with high NOD/SCID engraftment potential
      indicates the plasticity of hematopoietic precursors. CD133(+) stem cells might
      be useful for research and for clinical application.

PMID- 12799293
TI  - Adult bone marrow stem cells regenerate myocardium in ischemic heart disease.
AB  - Recent studies have demonstrated the existence of several populations of
      primitive cells in mouse and human bone marrow that have the capacity, both in
      vitro and in vivo, to give rise to cells of all three germ layers.
      Mesenchymal/stromal stem cells and hematopoietic stem cells are the leading
      candidates for this activity that some believe may recapitulate the potential of
      embryonic stem cells. Very little is known about the molecular controls for this
      adult stem cell activity commonly referred to as transdifferentiation or
      plasticity. Regeneration of a large number of cell types and tissues has been
      investigated with one of the most extensively studied being the myocardium. These
      studies involved ligation of the left coronary artery in adult mice and the
      direct injection or mobilization of bone marrow stem cells. Using this protocol
      we, and others, have observed the generation of new cardiomyocytes and
      endothelial cells in the zone of ischemic myocardium. This approach has
      progressed to clinical trials at several academic institutions. Although the
      preliminary findings from these trials do not permit unequivocal conclusions,
      they do suggest that safety and feasibility are not significant problems that
      would argue against extending these trials in a large, randomized, double-blinded
      study. When considerations such as these are addressed, cell therapy may become a
      new modality in the treatment of heart patients.

PMID- 12799294
TI  - Pluripotent stem cells identified in multiple murine tissues.
AB  - Pluripotential stem cells (PSCs) have been recently described in many tissues
      including skeletal muscle, brain, and bone marrow. However, the true nature of
      these cells is still unclear, and their precise definition has yet to be
      determined. We hypothesized that a common, rare population of PSCs with a broad
      tissue differentiation potential can be identified in multiple murine tissues and
      that these cells are capable of transdifferentiation into cells of different
      primordial germ layer origins in response to diverse microenvironmental cues. To
      examine this hypothesis, we isolated phenotypically defined cells from murine
      skeletal muscle and cultured these cells under different conditions tailored to
      promote differentiation into several cell types including myocytes. We report
      here that in conditions permissive for hematopoietic differentiation, muscle
      derived CD45(-)Sca-1(+)c-kit(-) cells differentiated into cells expressing
      hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal,
      and adipocytic differentiation, cells morphologically typical of these cell types
      expressing tissue-specific markers were identified 9-14 days in culture. When
      CD45(-)Sca-1(+)c-kit(-) cells from muscle or bone marrow were transplanted
      intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of
      these mice improved 28 days after transplantation relative to mice injected with
      vehicle alone, suggesting that these cells contributed to the appearance of
      functional neuronal cells that may have improved the ataxic condition
      characteristic of these mice. Phenotypic analysis of single cell suspensions
      prepared from brain, blood, and intestinal epithelium revealed the presence of
      CD45(-)Sca-1(+)c-kit(-) cells in varying degrees. These studies suggest that a
      phenotypically common, multipotent cell can be identified in different tissues
      and that this cell may represent a universal pluripotent stem cell residing at
      different levels in multiple murine tissues.

PMID- 12799295
TI  - Transplanted human cord blood cells give rise to hepatocytes in engrafted mice.
AB  - Recent studies suggest that rodent hepatocytes may be derived from hematopoietic
      stem cells. In the current study, the potential hematopoietic origin of
      hepatocytes was addressed using xenogeneic transplantation of human cord blood
      cells. CD34(+) or CD45(+) human cord blood cells were transplanted into
      "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months
      post-transplantation, livers of the recipient mice were cryosectioned and
      examined for evidence of human hepatocyte engraftment using RT-PCR to detect
      human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins,
      and fluorescence in situ hybridization (FISH) to detect the presence of human
      centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that
      21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen
      sections of transplanted mouse liver revealed the presence of engrafted cells
      positive for human centromeric DNA. That engrafted human cells functioned as
      hepatocytes was indicated by the expression of human albumin mRNA, as judged by
      RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded
      spontaneous cell fusion as the cause for the generation of human hepatocytes.
      Human cord blood cells can give rise to hepatocytes in a xenogeneic
      transplantation model. This model will be useful to further characterize the cord
      blood progenitors of hepatocytes.

PMID- 12799296
TI  - Early stages of hematopoietic differentiation.
AB  - Mouse bone marrow contains hematopoietic stem cells as well as progenitor cells,
      which are partially differentiated offspring of stem cells. We have utilized
      several approaches to separate progenitors from stem cells in order to
      characterize essential differences between these two stages of development. As a
      first approach, we utilized the supravital fluorescent dye rhodamine-123 (Rh-123)
      to distinguish quiescent stem cells (Rh-123(low)) from metabolically active
      progenitor cells (Rh-123(hi)). Analysis of megakaryocyte potential in a tissue
      culture assay demonstrated that Rh-123(hi) progenitor cells were capable of
      robust megakaryocyte differentiation, while Rh-123(low) stem cells produced fewer
      colonies containing megakaryocytes. Transplantation of the two cell populations
      into irradiated recipients revealed the opposite outcome, suggesting that the
      tissue culture assay failed to predict behavior in a transplant setting. We also
      evaluated functional potential of lymphoid progenitors isolated by selecting for
      differential expression of Thy-1.1 and c-kit. The potential of defined cell
      populations to differentiate as T or B lymphocytes in vivo was dependent upon the
      time post transplant at which animals were evaluated. These studies underscore
      the need for caution in the interpretation of lineage potentials evaluated by
      both in vitro and in vivo assays.

PMID- 12799297
TI  - Major age-related changes of mouse hematopoietic stem/progenitor cells.
AB  - To study age-related changes of mouse bone marrow (BM) cells and hematopoietic
      stem cells (HSCs), we isolated rhodamine-123(low) (Rh(low)) Thy1.1(low) Lin(-)Sca
      1(+) (TLS) HSCs from the BM of old mice and compared their functional
      characteristics to cells of the same phenotype isolated from young mice. We
      observed impaired recovery of B lymphocytes and decreased self-renewal in
      recipients of old Rh(low) cells compared to young Rh(low) cells. Blockade of Rh
      efflux using verapamil improved lymphoid reconstitution by enriched HSCs, and
      isolation of aged HSCs based on efflux of a fluorescent multi-drug resistance
      (MDR) substrate (Bodipy-verapamil) resulted in enrichment of HSC activity
      equivalent to that obtained with Rh. These observations suggest a complex
      relationship between MDR activity and HSC function during aging. To address
      whether the difference between young and aged donors was intrinsic to the HSC
      compartment or was due to a shift in HSC phenotype, we co-transplanted normal BM
      derived from young or old donors and followed repopulation simultaneously in the
      same recipient animals. In a parallel experiment, we co-transplanted HSCs
      purified from old donors with BM derived from young donors. In both experiments,
      transplants were given to both young and old recipients. The results show a clear
      defect in B-cell engraftment from either BM or HSCs of old donors, irrespective
      of the age of the recipient. In contrast, myeloid engraftment was predominantly
      derived from BM or HSCs derived from aged donors, again irrespective of recipient
      age. These data suggest a stem cell basis for B-cell immuno-senescence and the
      increased incidence of myelocytic leukemia in elderly people.

PMID- 12799298
TI  - Marrow stem cell potential within a continuum.
AB  - On the basis of our studies of the fluctuation of the hematopoietic stem cell
      phenotype with cell cycle trnsit, we hypothesize that the ability of marrow stem
      cells to convert to nonhematopoietic cells will also vary at different points in
      the cell cycle. The new biology of stem cells has an impact on many fields
      including developmental biology and stem cell biology and the clinical potential
      is enormous.

PMID- 12799299
TI  - CDCP1 is a novel marker for hematopoietic stem cells.
AB  - CDCP1 is a transmembrane protein that contains three CUB domains within the
      extracellular region and a hexalysine stretch within the cytoplasmic region.
      CDCP1 mRNA is highly expressed in lung and colon tumors and in the
      erythroleukemic cell line K562. To analyze CDCP1 protein expression, monoclonal
      antibodies against the extracellular domain of CDCP1 were raised. For this
      purpose, CDCP1 was overexpressed in NIH-3T3 cells. Balb/c mice were then
      immunized with the resultant cell line NIH-3T3/huCDCP1. After fusion of SP2/0
      cells with immune spleen cells, hybridoma clones were selected that secreted
      antibodies reacting with NIH-3T3/huCDCP1 cells but not with parental cells. Four
      antibodies (CUB1-CUB4) were obtained that fulfilled these criteria. Screening of
      peripheral blood cells revealed that the antibodies did not recognize mature
      lymphocytes, monocytes, granulocytes, erythrocytes, or platelets. In contrast,
      multi-color analyses revealed that CDCP1 protein is almost exclusively expressed
      on a subset of CD34(+) stem/progenitor cells in bone marrow. Transplantation of
      purified CDCP1(+) cells into NOD/SCID mice resulted in engraftment of human cells
      with multi-lineage differentiation potential, suggesting that CDCP1 is a novel
      marker for hematopoietic stem cells.

PMID- 12799300
TI  - Antibody W7C5 defines a CD109 epitope expressed on CD34+ and CD34- hematopoietic
      and mesenchymal stem cell subsets.
AB  - The cell surface antigen recognized by monoclonal antibody W7C5 is expressed at
      low levels on human CD34(+) and CD34(-) bone marrow stem cell populations but at
      high levels on fetal liver CD34(+) cells. To identify the recognized antigen, we
      performed partial amino acid sequence and MALDI analysis of purified W7C5
      antigens. The analyses revealed that MoAb W7C5 detects CD109, a recently cloned
      glycophosphatidylinositol-linked glycoprotein. The specificity of MoAb W7C5 was
      further confirmed by the selective recognition of CHO cells transfected with
      human CD109 cDNA.

PMID- 12799301
TI  - Unexpected potential of adult stem cells.

PMID- 12799302
TI  - Mesenchymal stem cells and hematopoietic stem cell transplantation.
AB  - Techniques have recently beome available to isolate and grow mesenchymal
      progenitors and to manipulate their growth under defined in vitro culture
      conditions. As a result mesenchymal stem cells can be rapidly expanded to numbers
      that are required for clinical application. This has allowed the clinical testing
      of culture-expanded MSCs in the context of hematopoietic stem cell
      transplantation. In this paper we discuss the role of MSCs in hematopoietic
      engraftment after transplantation.

PMID- 12799303
TI  - The mesenchymal stroma negatively regulates B cell lymphopoiesis through the
      expression of activin A.
AB  - The negative control of B cell generation is only partially resolved. We assessed
      the role of activin A in regulation of B lymphopoiesis in view of its specific
      inhibitory effects on tumor B lineage cells. Activin A is constitutively
      expressed in mouse hemopoietic organs and in cultured mesenchymal cell lines. We
      observed an inverse relationship between activin A titer and B lineage cell
      production. In the spleen, the red pulp exhibited a relatively higher abundance
      of the protein as compared with the lymphoid follicles, wherein B cell
      accumulation occurs. Furthermore, a specific shut off in activin A expression was
      observed in bone marrow and spleen following in vivo induction of B lymphocyte
      polyclonal activation. We further substantiated these in vivo observations by in
      vitro studies of primary bone marrow cultures, in which the expression of
      functional activin A was found to be diminished prior to the onset of B
      lymphopoiesis. The reduction in functional activin A is shown to concomitantly
      occur with spontaneous induction of the expression of activin A specific
      inhibitors. We therefore propose that the mesenchymal organ stroma expresses
      activin A that negatively controls B cell lymphopoiesis.

PMID- 12799304
TI  - P2Y2 receptor-stimulated release of prostaglandin E2 by rat inner medullary
      collecting duct preparations.
AB  - Extracellular nucleotides, acting through the P2Y2 receptor and the associated
      phosphoinositide-Ca2+ signaling pathway, inhibit AVP-stimulated osmotic water
      permeability in rat inner medullary collecting duct (IMCD). Because a rise in
      intracellular Ca2+ is frequently associated with enhanced arachidonic acid
      metabolism, we examined the effect of activation of the P2Y2 receptor on release
      of PGE2 in freshly prepared rat IMCD suspensions. Unstimulated IMCD released
      moderate, but significant, amounts of PGE2, which were more sensitive to
      cyclooxygenase (COX)-2 than COX-1 inhibition. Agonist activation of P2Y2 receptor
      by adenosine 5'-O-(3-thiotriphosphate) enhanced release of PGE2 from IMCD in a
      time- and concentration-dependent fashion. Purinergic-stimulated release of PGE2
      was completely blocked by nonspecific COX inhibitors (flurbiprofen and 2
      acetoxyphenylhept-2-ynyl sulfide). Differential COX inhibition studies revealed
      that purinergic-stimulated release of PGE2 was more sensitive to a COX-1-specific
      inhibitor (valeroyl salicylate) than a COX-2-specific inhibitor (NS-398). Thus
      purinergic stimulation resulted in significantly more release of PGE2 in the
      presence of COX-2 inhibitor than COX-1 inhibitor. If it is assumed that increased
      release of PGE2 is related to its increased production, our results suggest that
      purinergic stimulation of IMCD results in enhanced production and release of PGE2
      in a COX-1-dependent fashion. Because PGE2 is known to affect transport of water,
      salt, and urea in IMCD, interaction of the purinergic system with the prostanoid
      system in IMCD can modulate handling of water, salt, and urea by IMCD and, thus,
      may constitute an AVP-independent regulatory mechanism.

PMID- 12799305
TI  - Partial bladder outlet obstruction alters Ca2+ sensitivity of force, but not of
      MLC phosphorylation, in bladder smooth muscle.
AB  - Partial bladder outlet obstruction in the rabbit produces changes in bladder
      function similar to those seen clinically in patients with obstructive
      uropathies. Whole organ function is significantly altered, as are the smooth
      muscle cells inside the bladder wall. This study was designed to determine
      whether outlet obstruction alters smooth muscle function at the level of
      contractile filaments. Rabbit bladders were partially obstructed for 2 wk. Triton
      X-100 was used to provide a detergent-skinned bladder smooth muscle preparation
      that would allow control of the intracellular environment while the ability to
      shorten and develop force is maintained. Ca2+-force and Ca2+-myosin light chain
      (MLC) phosphorylation relations and maximal velocity of shortening were
      determined. The Ca2+ sensitivity of force was significantly lower in tissues from
      animals subjected to outlet obstruction compared with tissues from control
      animals. In contrast, no difference was noted in the Ca2+ sensitivity of MLC
      phosphorylation. Maximal levels of stress and MLC phosphorylation were similar in
      both animal groups. Maximal velocity of shortening was significantly slower in
      tissues from outlet-obstructed animals at all Ca2+ concentrations compared with
      tissues from control animals. Ultrastructurally, detergent skinning had little
      effect on structural integrity. Moreover, tissues from obstructed animals showed
      an increase in the number of sarcolemmal attachment plaque structures. We suggest
      that partial bladder outlet obstruction produces deleterious (e.g., decrease in
      Ca2+ sensitivity of force) and compensatory (e.g., increase in membrane
      attachment plaques) changes in bladder smooth muscle cells.

PMID- 12799306
TI  - Effect of salt on hypertension and oxidative stress in a rat model of diet
      induced obesity.
AB  - High-salt diet is known to induce or aggravate hypertension in animal models of
      hypertension and in humans. When Sprague-Dawley rats (n = 60) are fed a
      moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half
      develop obesity [obesity prone (OP)] and mild hypertension, whereas the other
      half [obesity resistant (OR)] maintain body weight equivalent to a low-fat
      control (C) and are normotensive. The aim of this study was to test the effect of
      high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity,
      oxidative stress, and renal function. Both 2 and 4% NaCl induced an early
      increase in systolic blood pressure of OP but not OR or C rats. High-salt intake
      induced an increase in the size and reduction in number of adipocytes,
      concomitant to a twofold increase in circulating leptin in OP rats. Aortic
      superoxide generation indicated a 2.8-fold increase in the OP high-salt vs.
      normal-salt groups, whereas urine isoprostanes were not significantly increased.
      Also, hydroxynonenal protein adducts in the kidney were highly increased in OP
      rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine
      albumin was increased threefold in the OP on 2% NaCl and fourfold in the same
      group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of
      glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet
      accelerated the development but did not increase the severity of hypertension;
      high salt increased oxidative stress in the vasculature and kidney and induced
      kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt
      displayed adipocyte hypertrophy and increased leptin production.

PMID- 12799307
TI  - Effects of pathophysiological concentrations of albumin on NHE3 activity and cell
      proliferation in primary cultures of human proximal tubule cells.
AB  - The progression of renal disease correlates strongly with hypertension and the
      degree of proteinuria, suggesting a link between excessive Na+ reabsorption and
      exposure of the proximal tubule to protein. The present study investigated the
      effects of albumin on cell growth and Na+ uptake in primary cultures of human
      proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to
      134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of
      apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total 22Na+ uptake to
      119.1 +/- 6.3% (P = 0.005) and 115.6 +/- 5.3% (P < 0.006) of control levels,
      respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3)
      activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P
      < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal
      microscopy with a novel antibody raised against the predicted extracellular NH2
      terminus of human NHE3, we observed in nonpermeabilized cells that exposure of
      PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 +/
      2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels,
      respectively. This effect was paralleled by significant increases in NHE3 in the
      subplasmalemmal region as measured in permeabilized cells. These albumin-induced
      increases in expression and activity of NHE3 in PTC suggest a possible mechanism
      for Na+ retention in response to proteinuria.

PMID- 12799308
TI  - Increasing cell membrane potential and GABAergic activity inhibits malignant
      hepatocyte growth.
AB  - Increasing hepatocyte membrane potentials by augmenting GABAergic activity
      inhibits nonmalignant hepatocyte proliferative activity. The objectives of this
      study were to document 1) potential differences (PDs) of four malignant
      hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines,
      and 3) effects of restoring malignant hepatocyte PDs to levels approximating
      those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in
      nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with
      a fluorescent voltage-sensitive dye and GABAA receptor expression by RT-PCR and
      Western blot analyses. Compared with nonmalignant human hepatocytes, all four
      malignant cell lines were significantly depolarized (P < 0.0001, respectively).
      Only PLC/PRF/5 cells had detectable GABAA-beta3 receptor mRNA expression and all
      cell lines were negative for GABAA-beta3 receptor protein by Western blot
      analysis. Stable transfection of Chang cells with GABAA-beta3 receptor cDNA
      resulted in significant increases in PD and decreases in proliferative activity
      as manifest by decreased [3H]thymidine and bromodeoxyurieine incorporation rates,
      4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate
      activity, a lower mitotic index, prolongation of cell-doubling times, and
      attenuated growth patterns compared with cells transfected with vector alone.
      Colony formation in soft agar and the number of abnormal mitoses were also
      significantly decreased in GABAA-beta3 receptor transfected cells. The results of
      this study indicate 1) relative to healthy hepatocytes, malignant hepatocytes are
      significantly depolarized, 2) GABAA-beta3 receptor expression is absent in
      malignant hepatocyte cell lines, and 3) increasing the PD of malignant
      hepatocytes is associated with less proliferative activity and a loss of
      malignant features.

PMID- 12799309
TI  - MAPK mediates PKC-dependent contraction of cat esophageal and lower esophageal
      sphincter circular smooth muscle.
AB  - Esophageal (ESO) circular muscle contraction and lower esophageal sphincter (LES)
      tone are PKC dependent. Because MAPKs may be involved in PKC-dependent
      contraction, we examined ERK1/ERK2 and p38 MAPKs in ESO and LES. In permeabilized
      LES muscle cells, ERK1/2 antibodies reduced 1,2-dioctanoylglycerol (DG)- and
      threshold ACh-induced contraction, which are PKC dependent, but not maximal ACh,
      which is calmodulin dependent. LES tone was reduced by the ERK1/2 kinase
      inhibitor PD-98059 and by the p38 MAPK inhibitor SB-203580. In permeable ESO
      cells, ACh contraction was reduced by ERK1/ERK2 and p38 MAPK antibodies and by PD
      98059 and SB-203580. ACh increased MAPK activity and phosphorylation of MAPK and
      of p38 MAPK. The 27-kDa heat shock protein (HSP27) antibodies reduced ACh
      contraction. HSP27 and p38 MAPK antibodies together caused no greater inhibition
      than either one alone. p38 MAPK and HSP27 coprecipitated after ACh stimulation,
      suggesting that HSP27 is linked to p38 MAPK. These data suggest that PKC
      dependent contraction in ESO and LES is mediated by the following two distinct
      MAPK pathways: ERK1/2 and HSP27-linked p38 MAPK.

PMID- 12799310
TI  - Glutamine preserves protein synthesis and paracellular permeability in Caco-2
      cells submitted to "luminal fasting".
AB  - This study used polarized cell line Caco-2 as a model of human enterocytes to
      determine: 1) whether deprivation of nutrients on the apical (luminal) side of
      the epithelium (fasting) alters protein synthesis in enterocytes; 2) if so,
      whether glutamine can attenuate the effects of fasting; and 3) whether the
      effects of glutamine depend on its route (i.e., apical vs. basolateral) of
      supply. Caco-2 cells were submitted to nutrient deprivation on the apical side to
      mimic the effects of fasting, whereas the basolateral side of the epithelium
      remained exposed to regular medium. Cells were then incubated with [2H3]leucine
      with or without glutamine, and the fractional synthesis rate (FSR) of total cell
      protein was determined from [2H3]leucine enrichments in protein-bound and
      intracellular free leucine measured by gas chromatography/mass spectrometry. A 24
      h apical nutrient deprivation (luminal fasting) was associated with a decline in
      intracellular glutamine, glutamate, and glutathione concentrations (-38, -40, and
      -40%, respectively), protein FSR (-20%), and a rise in passage of dextran, an
      index of transepithelial permeability. In fasted cells, basolateral or luminal
      glutamine supplementation did not alter the glutathione pool, but it restored
      protein FSR and improved permeability. The effects of glutamine were abolished by
      6-diazo-oxo-l-norleucine, an inhibitor of glutaminase, and was mimicked by
      glutamate. We conclude that in Caco-2 cells, protein synthesis depends on
      nutrient supply on the apical side, and glutamine regardless of the route of
      supply corrects some of the deleterious effects of fasting in a model of human
      enterocytes through its deamidation into glutamate.

PMID- 12799311
TI  - ETA and ETB receptor function in pancreatitis-associated microcirculatory
      failure, inflammation, and parenchymal injury.
AB  - The role of endothelin (ET)A and ETB receptor function in experimental
      pancreatitis is still not fully understood. Using a rat model of sodium
      taurocholate-induced pancreatitis and intravital microscopy, we therefore studied
      whether selective inhibition of ETA receptor function or combined ETA and ETB
      receptor blockade affects the development of pancreatitis-associated
      microcirculatory failure, inflammation, and parenchymal injury. Pretreatment with
      10 mg/kg body wt of a combined ETA/B receptor antagonist, which is thought to
      mediate a simultaneous inhibition of both receptors, did not attenuate the
      pancreatitis-induced microcirculatory failure, inflammatory response, and
      parenchymal tissue injury. In contrast, pretreatment with a low concentration of
      the combined ETA/B receptor antagonist (4 mg/kg body wt), which predominantly
      inhibits the ETA receptor, revealed an improvement of some microcirculatory
      disorders and a significant attenuation of leukocyte recruitment and tissue
      injury. Furthermore, pretreatment with a selective ETA receptor antagonist (1
      microg/kg body wt) almost abolished pancreatitis-associated capillary
      constriction, restored functional capillary density, and, consequently, improved
      overall nutritive perfusion. Importantly, the maintenance of an appropriate
      microcirculation by selective ETA receptor inhibition was accompanied by a
      significant attenuation of the inflammation-associated leukocytic response and by
      a marked reduction of parenchymal injury. Thus our study indicates that
      pancreatitis-associated development of microcirculatory failure, inflammation,
      and parenchymal injury is caused by ETs coupling onto the ETA receptor, which
      therefore may represent a promising target for novel strategies in the treatment
      of pancreatitis.

PMID- 12799312
TI  - C-peptide increases forearm blood flow in patients with type 1 diabetes via a
      nitric oxide-dependent mechanism.
AB  - Proinsulin C-peptide has been shown to increase muscle blood flow in type 1
      diabetic patients. The underlying mechanism is not fully understood. The aim of
      this study was to evaluate if the vasodilator effect of C-peptide is mediated by
      nitric oxide (NO). Eleven type 1 diabetic patients were studied two times and
      randomized to administration of intravenous and intra-arterial infusion of C
      peptide or saline. Forearm blood flow (FBF) was measured by venous occlusion
      plethysmography during infusion of C-peptide or saline before, during, and after
      NO synthase (NOS) blockade. Endothelium-dependent and -independent vasodilatation
      was evaluated by administration of acetylcholine and sodium nitroprusside,
      respectively. FBF increased by 35% during intravenous C-peptide (P < 0.01) but
      not during saline infusion (-2%, not significant). NOS blockade resulted in a
      more pronounced reduction in FBF during intravenous C-peptide than during saline
      infusion (-41 vs. -26%, P < 0.05). Intra-arterial C-peptide failed to increase
      FBF during NOS blockade. However, when C-peptide was given after the recovery
      from NOS blockade, FBF rose by 30% (P < 0.001). The vasodilator effects of
      acetylcholine and nitroprusside were not influenced by C-peptide. It is concluded
      that the stimulatory effect of C-peptide on FBF in type 1 diabetic patients is
      mediated via the NO system and that C-peptide increases basal endothelial NO
      levels.

PMID- 12799313
TI  - Effects of GH on urea, glucose and lipid metabolism, and insulin sensitivity
      during fasting in GH-deficient patients.
AB  - Fasting-related states of distress pose major health problems, and growth hormone
      (GH) plays a key role in this context. The present study was designed to assess
      the effects of GH on substrate metabolism and insulin sensitivity during short
      term fasting. Six GH-deficient adults underwent 42.5 h of fasting on two
      occasions, with and without concomitant GH replacement. Palmitate and urea fluxes
      were measured with the steady-state isotope dilution technique after infusion of
      [9,10-3H]palmitate and [13C]urea. During fasting with GH replacement, palmitate
      concentrations and fluxes increased by 50% [palmitate: 378 +/- 42 (GH) vs. 244 +/
      12 micromol/l, P < 0.05; palmitate: 412 +/- 58 (GH) vs. 276 +/- 42 microM, P =
      0.05], and urea turnover and excretion decreased by 30-35% [urea rate of
      appearance: 336 +/- 22 (GH) vs. 439 +/- 43 micromol. kg-1. h-1, P < 0.01; urea
      excretion: 445 +/- 43 (GH) vs. 602 +/- 74 mmol/24 h, P < 0.05]. Insulin
      sensitivity (determined by a euglycemic hyperinsulinemic clamp) was significantly
      decreased [M value: 1.26 +/- 0.06 (GH) vs. 2.07 +/- 0.22 mg. kg-1. min-1, P <
      0.01] during fasting with GH replacement. In conclusion, continued GH replacement
      during fasting in GH-deficient adults decreases insulin sensitivity, increases
      lipid utilization, and conserves protein.

PMID- 12799314
TI  - Defective protein histidine phosphorylation in islets from the Goto-Kakizaki
      diabetic rat.
AB  - We recently described novel regulatory roles for protein histidine
      phosphorylation of key islet proteins (e.g., nucleoside diphosphate kinase and
      succinyl thiokinase) in insulin secretion from the islet beta-cell (Kowluru A.
      Diabetologia 44: 89-94, 2001; Kowluru A, Tannous M, and Chen HQ. Arch Biochem
      Biophys 398: 160-169, 2002). In this context, we also characterized a novel, ATP-
      and GTP-sensitive protein histidine kinase in isolated beta-cells that catalyzed
      the histidine phosphorylation of islet (endogenous) proteins as well as
      exogenously added histone 4, and we implicated this kinase in the activation of
      islet endogenous G proteins (Kowluru A. Biochem Pharmacol 63: 2091-2100, 2002).
      In the present study, we describe abnormalities in ATP- or GTP-mediated histidine
      phosphorylation of nucleoside diphosphate kinase in islets derived from the Goto
      Kakizaki (GK) rat, a model for non-insulin-dependent diabetes. Furthermore, we
      provide evidence for a marked reduction in the activities of ATP- or GTP
      sensitive histidine kinases in GK rat islets. On the basis of these observations,
      we propose that alterations in protein histidine phosphorylation could contribute
      toward insulin-secretory abnormalities demonstrable in the diabetic islet.

PMID- 12799315
TI  - Influence of diet on the modeling of adipose tissue triglycerides during growth.
AB  - We have studied the accretion of lipids in growing mice. We measured the rates of
      synthesis and degradation of triglycerides in epididymal fat pads of mice
      maintained for 44 days on a low-fat, high-carbohydrate diet (I) or a high-fat,
      low-carbohydrate diet (II). 2H2O was added to the drinking water for 14 days.
      Rates of incorporation/washout of 2H to/from C1 of triglyceride-glycerol showed
      that triglyceride synthesis was greater than triglyceride degradation (net
      triglyceride balance was approximately 2.5 times greater in II than in I). The
      data also show that the contribution of de novo lipogenesis to triglyceride-bound
      palmitate was approximately 3 times greater in I than in II. This was consistent
      with a greater relative intake of carbohydrate in I vs. II. The rates of
      incorporation and washout of newly synthesized (2H-labeled) palmitate into and
      from triglycerides were also measured. Those data suggested a remodeling of
      triglyceride-bound fatty acids. On measuring the profile of triglyceride-bound
      fatty acids, we observed a decrease in the relative abundance of triglyceride
      bound palmitate and stearate and an increase in triglyceride-bound oleate and
      linoleate. This was observed in I and II. In summary, diet substantially affects
      the deposition and modeling of triglycerides in adipose tissue during growth.
      2H2O can be used to examine the mechanisms responsible for the accumulation of
      triglycerides, e.g., factors that affect 1) triglyceride synthesis and
      degradation and 2) the source of fatty acids that are used in esterification.

PMID- 12799316
TI  - Prevention of glycogen supercompensation prolongs the increase in muscle GLUT4
      after exercise.
AB  - Exercise induces an increase in GLUT4 in skeletal muscle with a proportional
      increase in glucose transport capacity. This adaptation results in enhanced
      glycogen accumulation, i.e., "supercompensation," in response to carbohydrate
      feeding after glycogen-depleting exercise. The increase in GLUT4 reverses within
      40 h after exercise in carbohydrate-fed rats. The purpose of this study was to
      determine whether prevention of skeletal muscle glycogen supercompensation after
      exercise results in maintenance of the increases in GLUT4 and the capacity for
      glycogen supercompensation. Rats were exercised by means of three daily bouts of
      swimming. GLUT4 mRNA was increased approximately 3-fold and GLUT4 protein was
      increased approximately 2-fold 18 h in epitrochlearis muscle after exercise.
      These increases in GLUT4 mRNA and protein reversed completely within 42 h after
      exercise in rats fed a high-carbohydrate diet. In contrast, the increases in
      GLUT4 protein, insulin-stimulated glucose transport, and increased capacity for
      glycogen supercompensation persisted unchanged for 66 h in rats fed a
      carbohydrate-free diet that prevented glycogen supercompensation after exercise.
      GLUT4 mRNA was still elevated at 42 h but had returned to baseline by 66 h after
      exercise in rats fed the carbohydrate-free diet. Glycogen-depleted rats fed
      carbohydrate 66 h after exercise underwent muscle glycogen supercompensation with
      concomitant reversal of the increase in GLUT4. These findings provide evidence
      that prevention of glycogen supercompensation after exercise results in
      persistence of exercise-induced increases in GLUT4 protein and enhanced capacity
      for glycogen supercompensation.

PMID- 12799317
TI  - Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated
      rat skeletal muscle.
AB  - Skeletal muscle insulin sensitivity improves with short-term reduction in calorie
      intake. The goal of this study was to evaluate changes in the abundance and
      phosphorylation of Akt1 and Akt2 as potential mechanisms for enhanced insulin
      action after 20 days of moderate calorie restriction [CR; 60% of ad libitum (AL)
      intake] in rat skeletal muscle. We also assessed changes in the abundance of SH2
      domain-containing inositol phosphatase (SHIP2), a negative regulator of insulin
      signaling. Fisher 344 x Brown Norway rats were assigned to an AL control group or
      a CR treatment group for 20 days. Epitrochlearis muscles were dissected and
      incubated with or without insulin (500 microU/ml). Total Akt serine and threonine
      phosphorylation was significantly increased by 32 (P < 0.01) and 30% (P < 0.005)
      in insulin-stimulated muscles from CR vs. AL. Despite an increase in total Akt
      phosphorylation, there was no difference in Akt1 serine or Akt1 threonine
      phosphorylation between CR and AL insulin-treated muscles. However, there was a
      30% decrease (P < 0.05) in Akt1 abundance for CR vs. AL. In contrast, there was
      no change in Akt2 protein abundance, and there was a 94% increase (P < 0.05) in
      Akt2 serine phosphorylation and an increase of 75% (P < 0.05) in Akt2 threonine
      phosphorylation of insulin-stimulated CR muscles compared with AL. There was no
      diet effect on SHIP2 abundance in skeletal muscle. These results suggest that,
      with brief CR, enhanced Akt2 phosphorylation may play a role in increasing
      insulin sensitivity in rat skeletal muscles.

PMID- 12799318
TI  - N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in
      vivo: possible role of oxidative stress.
AB  - Exposure to high concentrations of glucose and insulin results in insulin
      resistance of metabolic target tissues, a characteristic feature of type 2
      diabetes. High glucose has also been associated with oxidative stress, and
      increased levels of reactive oxygen species have been proposed to cause insulin
      resistance. To determine whether oxidative stress contributes to insulin
      resistance induced by hyperglycemia in vivo, nondiabetic rats were infused with
      glucose for 6 h to maintain a circulating glucose concentration of 15 mM with and
      without coinfusion of the antioxidant N-acetylcysteine (NAC), followed by a 2-h
      hyperinsulinemic-euglycemic clamp. High glucose (HG) induced a significant
      decrease in insulin-stimulated glucose uptake [tracer-determined disappearance
      rate (Rd), control 41.2 +/- 1.7 vs. HG 32.4 +/- 1.9 mg. kg-1. min-1, P < 0.05],
      which was prevented by NAC (HG + NAC 45.9 +/- 3.5 mg. kg-1. min-1). Similar
      results were obtained with the antioxidant taurine. Neither NAC nor taurine alone
      altered Rd. HG caused a significant (5-fold) increase in soleus muscle protein
      carbonyl content, a marker of oxidative stress that was blocked by NAC, as well
      as elevated levels of malondialdehyde and 4-hydroxynonenal, markers of lipid
      peroxidation, which were reduced by taurine. In contrast to findings after long
      term hyperglycemia, there was no membrane translocation of novel isoforms of
      protein kinase C in skeletal muscle after 6 h. These data support the concept
      that oxidative stress contributes to the pathogenesis of hyperglycemia-induced
      insulin resistance.

PMID- 12799319
TI  - Characterization of insulin signaling in rat retina in vivo and ex vivo.
AB  - Insulin receptor (IR) signaling cascades have been studied in many tissues, but
      retinal insulin action has received little attention. Retinal IR signaling and
      activity were investigated in vivo in rats that were freely fed, fasted, or
      injected with insulin by phosphotyrosine immunoblotting and by measuring kinase
      activity. A retina explant system was utilized to investigate the IR signaling
      cascade, and immunohistochemistry was used to determine which retinal cell layers
      respond to insulin. Basal IR activity in the retina was equivalent to that in
      brain and significantly greater than that of liver, and it remained constant
      between freely fed and fasted rats. Furthermore, IR signaling increased in the
      retina after portal vein administration of supraphysiological doses of insulin.
      Ex vivo retinas responded to 10 nM insulin with IR beta-subunit (IRbeta) and IR
      substrate-2 (IRS-2) tyrosine phosphorylation and AktSer473 phosphorylation. The
      retina expresses mRNA for all three Akt isoforms as determined by in situ
      hybridization, and insulin specifically increases Akt-1 kinase activity. Phospho
      AktSer473 immunoreactivity increases in retinal nuclear cell layers with insulin
      treatment. These results demonstrate that the retinal IR signaling cascade to Akt
      1 possesses constitutive activity, and that exogenous insulin further stimulates
      this prosurvival pathway. These findings may have implications in understanding
      normal and dysfunctional retinal physiology.

PMID- 12799320
TI  - Genetically altered mouse models: the good, the bad, and the ugly.
AB  - Targeted gene disruption in mice is a powerful tool for generating murine models
      for human development and disease. While the human genome program has helped to
      generate numerous candidate genes, few genes have been characterized for their
      precise in vivo functions. Gene targeting has had an enormous impact on our
      ability to delineate the functional roles of these genes. Many gene knockout
      mouse models faithfully mimic the phenotypes of the human diseases. Because some
      models display an unexpected or no phenotype, controversy has arisen about the
      value of gene-targeting strategies. We argue in favor of gene-targeting
      strategies, provided they are used with caution, particularly in interpreting
      phenotypes in craniofacial and oral biology, where many genes have pleiotropic
      roles. The potential pitfalls are outweighed by the unique opportunities for
      developing and testing different therapeutic strategies before they are
      introduced into the clinic. In the future, we believe that genetically engineered
      animal models will be indispensable for gaining important insights into the
      molecular mechanisms underlying development, as well as disease pathogenesis,
      diagnosis, prevention, and treatment.

PMID- 12799321
TI  - Genomics of oral bacteria.
AB  - Advances in bacterial genetics came with the discovery of the genetic code,
      followed by the development of recombinant DNA technologies. Now the field is
      undergoing a new revolution because of investigators' ability to sequence and
      assemble complete bacterial genomes. Over 200 genome projects have been completed
      or are in progress, and the oral microbiology research community has benefited
      through projects for oral bacteria and their non-oral-pathogen relatives. This
      review describes features of several oral bacterial genomes, and emphasizes the
      themes of species relationships, comparative genomics, and lateral gene transfer.
      Genomics is having a broad impact on basic research in microbial pathogenesis,
      and will lead to new approaches in clinical research and therapeutics. The oral
      microbiota is a unique community especially suited for new challenges to sequence
      the metagenomes of microbial consortia, and the genomes of uncultivable bacteria.

PMID- 12799322
TI  - Mast cells and oral inflammation.
AB  - Mast cells are mobile granule-containing secretory cells that are distributed
      preferentially about the microvascular endothelium in oral mucosa and dental
      pulp. The enzyme profile of mast cells in oral tissues resembles that of skin,
      with most mast cells expressing the serine proteases tryptase and chymase. Mast
      cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis
      factor-alpha in their granules, and release of this promotes leukocyte
      infiltration during evolving inflammation in several conditions, including lichen
      planus, gingivitis, pulpitis, and periapical inflammation, through induction of
      endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of
      other mediators exerts potent immunoregulatory effects on other cell types, while
      several T-lymphocyte-derived cytokines influence mast cell migration and mediator
      release. Mast cell proteases may contribute to alterations in basement membranes
      in inflammation in the oral cavity, such as the disruptions that allow cytotoxic
      lymphocytes to enter the epithelium in oral lichen planus. A close relationship
      exists among mast cells, neural elements, and laminin, and this explains the
      preferential distribution of mast cells in tissues. Mast cells are responsive to
      neuropeptides and, through their interaction with neural elements, form a neural
      immune network with Langerhans cells in mucosal tissues. This facilitates mast
      cell degranulation in response to a range of immunological and non-immunological
      stimuli. Because mast cells play a pivotal role in inflammation, therapies that
      target mast cell functions could have value in the treatment of chronic
      inflammatory disorders in the oral cavity.

PMID- 12799323
TI  - Oral sequelae of head and neck radiotherapy.
AB  - In addition to anti-tumor effects, ionizing radiation causes damage in normal
      tissues located in the radiation portals. Oral complications of radiotherapy in
      the head and neck region are the result of the deleterious effects of radiation
      on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature,
      and temporomandibular joints. The clinical consequences of radiotherapy include
      mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and
      trismus. Mucositis and taste loss are reversible consequences that usually
      subside early post-irradiation, while hyposalivation is normally irreversible.
      Furthermore, the risk of developing radiation caries and osteoradionecrosis is a
      life-long threat. All these consequences form a heavy burden for the patients and
      have a tremendous impact on their quality of life during and after radiotherapy.
      In this review, the radiation-induced changes in healthy oral tissues and the
      resulting clinical consequences are discussed.

PMID- 12799324
TI  - Prevention and treatment of the consequences of head and neck radiotherapy.
AB  - The location of the primary tumor or lymph node metastases dictates the inclusion
      of the oral cavity, salivary glands, and jaws in the radiation treatment portals
      for patients who have head and neck cancer. The clinical sequelae of the
      radiation treatment include mucositis, hyposalivation, loss of taste,
      osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose
      limiting and have a tremendous effect on the patient's quality of life. Most
      treatment protocols to prevent these sequelae are still based on clinical
      experience, but alternatives based on fundamental basic and clinical research are
      becoming more and more available. Many of these alternatives either need further
      study before they can be incorporated into the protocols commonly used to prevent
      and treat the radiation-related oral sequelae or await implementation of these
      protocols. In this review, the various possibilities for prevention and/or
      treatment of radiation-induced changes in healthy oral tissues and their
      consequences are discussed.

PMID- 12799325
TI  - Oral Helicobacter pylori: can we stomach it?
AB  - Helicobacter pylori infection is one of the most common in man. The bacterium
      primarily resides in the human stomach, where it plays a significant role in
      gastric disease. If the spread of H. pylori is to be prevented, an understanding
      of the transmission process is essential. The oral cavity has been proposed as a
      reservoir for gastric H. pylori, which has been detected by culture and PCR in
      both dental plaque and saliva. This review will discuss the evidence for the role
      of the oral cavity in the transmission of gastric H. pylori. Moreover, the
      difficulties encountered in addressing this topic, possible directions for future
      research, and the implications for the dental profession are discussed.

PMID- 12799326
TI  - Residency program at Michael E. DeBakey Department of Surgery, Baylor College of
      Medicine.

PMID- 12799327
TI  - Surgical treatment of appendiceal mucocele.
AB  - HYPOTHESIS: Clinical presentation of appendiceal mucocele is related to
      malignancy and can influence surgical approach. DESIGN: Retrospective study.
      SETTING: Tertiary referral center. PATIENTS: All cases of primary appendiceal
      mucoceles (simple mucocele, cystadenoma, cystadenocarcinoma) diagnosed between
      1976 and 2000 were reviewed. There were 135 patients, 74 of whom were female.
      Mean age at diagnosis was 59 years. Mean follow-up was more than 6 years.
      INTERVENTIONS: A total of 129 patients underwent surgery, consisting of
      appendectomy (22 patients), right hemicolectomy (25 patients), or more extensive
      procedures (82 patients). MAIN OUTCOME MEASURES: Clinical, diagnostic, and
      surgical variables were statistically compared with postoperative morbidity and
      mortality and the presence of malignancy. P<.05 was considered significant.
      RESULTS: The presence of symptoms was associated with malignancy (58% vs 15%,
      P<.001), particularly abdominal pain (56% vs 29%, P =.005) and weight loss (77%
      vs 31%, P =.002). Abdominal mass was also associated with malignancy (86% vs 25%,
      P<.001). Moreover, pseudomyxoma peritonei and mucocele extravasation were
      associated with malignancy (95% vs 13%, P<.001, and 83% vs 15%, P<.001,
      respectively). The lesion size was not associated with malignancy; however,
      cystadenomas were significantly larger than simple mucoceles (8.1 cm vs 4.1 cm,
      P<.001), and no cystadenoma was less than 2 cm in largest diameter. CONCLUSIONS:
      A number of clinical, diagnostic, and intraoperative findings are associated with
      malignant mucoceles. All mucoceles greater than 2 cm should be excised to remove
      premalignant lesions.

PMID- 12799328
TI  - The role of temporary inferior vena cava filters in critically ill surgical
      patients.
AB  - HYPOTHESIS: Prophylactic temporary inferior vena cava (IVC) filters are safe and
      effective in critically ill patients at high risk for venous thromboembolism.
      DESIGN: Prospective cohort study. SETTING: Urban level I trauma center. SUBJECTS:
      Multiple-trauma patients and critically ill surgical patients undergoing
      prophylactic temporary IVC filter placement. All patients were at high risk for
      venous thromboembolism but had contraindications to low-dose heparin therapy.
      INTERVENTIONS: The interventional radiologist used the femoral or internal
      jugular approach to place a removable IVC filter in all patients. The filter was
      removed when the patient could safely be treated with heparin. If the filter
      could not be removed by 14 days, it was relocated to prevent incorporation
      precluding retrieval. MAIN OUTCOME MEASURES: Complications of filter insertion
      and removal, deep venous thrombosis, and pulmonary embolism. RESULTS: From May 1,
      2001, to October 1, 2002, 44 patients underwent placement of temporary IVC
      filters. Thirty-seven patients (84%) were severely injured. The mean +/- SD age
      was 37 +/- 3 years, and 55% were men. The mean +/- SD Injury Severity Score of
      the trauma patients was 33 +/- 2, and all had blunt injury. There were no
      complications associated with filter insertion or removal. Nine patients required
      filter relocation prior to retrieval. Three filters could not be removed: 2
      secondary to significant clots trapped below the filter and 1 because of
      angulation resulting in the inability to grasp the filter. There were no
      documented instances of venous thromboembolism following IVC filter placement and
      removal. CONCLUSIONS: Temporary IVC filters are safe and effective in critically
      ill surgical and trauma patients and allow an aggressive approach to prevention
      of venous thromboembolism in this challenging group of patients.

PMID- 12799329
TI  - Temporal patterns of postoperative complications.
AB  - HYPOTHESIS: A variety of major complications occur after intra-abdominal
      operations. Knowledge of when specific complications occur during the
      postoperative period would be useful in their diagnosis, prevention, and
      management. Our aim was to determine the incidence of major complications during
      specific postoperative intervals. DESIGN: One thousand twenty-one patients
      undergoing intra-abdominal operations were studied postoperatively as part of a
      randomized clinical trial. Thirteen defined major complications were sought at
      the following specific intervals: less than 1, 1 through 3, 4 through 7, and 8
      through 30 days after the operation. SETTING: Cooperative trial from 15 Veterans
      Affairs medical centers. INTERVENTIONS: Intra-abdominal aortic, gastric, biliary,
      and colonic procedures. MAIN OUTCOME MEASUREMENTS: Major postoperative
      complications. RESULTS: Four hundred thirty-five major complications were
      diagnosed within 30 days of the patients' being operated on. Seventy-four (17%)
      occurred within 1 day, 185 (43%) between 1 and 3 days, 72 (17%) between 4 and 7
      days, and 104 (24%) between 8 and 30 days. Three deaths (8%) occurred within 1
      day, 3 (8%) in 1 through 3 days, 4 (11%) in 4 through 7 days, and 27 (73%) in 8
      through 30 days. The greatest risk of hypotension (43%), myocardial infarction
      (47%), and respiratory depression (55%) was within 1 day. The highest incidence
      of congestive heart failure (46%), pulmonary embolus (50%), and respiratory
      failure (76%) occurred at 1 through 3 days. Pneumonia (38%) was most common at 4
      through 7 days. Cerebrovascular accident (53%) and sepsis (71%) occurred
      preponderantly at 8 through 30 days. Renal failure had a bimodal distribution
      with maxima at 1 through 3 days (31%) and 8 through 30 days (56%). The risk of
      cardiac arrhythmia and gastrointestinal tract bleeding was similar throughout all
      intervals. CONCLUSIONS: While major complications occur throughout the
      postoperative period, the highest incidence is 1 through 3 days after the
      operation. However, specific complications occur in the following distinct
      temporal patterns: early postoperative, several days after the operation,
      throughout the postoperative period, and in the late postoperative period.
      Knowledge of these patterns should aid clinical management.

PMID- 12799330
TI  - Directed parathyroidectomy: feasibility and performance in 100 consecutive
      patients with primary hyperparathyroidism.
AB  - HYPOTHESIS: Directed parathyroidectomy (DP) can be successfully completed in most
      patients with primary hyperparathyroidism. DESIGN AND SETTING: Retrospective
      review at a tertiary referral center. PATIENTS: One hundred consecutive patients
      with untreated, sporadic primary hyperparathyroidism operated on by a single
      surgeon from April 1, 1999, through December 31, 2001. INTERVENTIONS: Following
      preoperative imaging with sestamibi scintigraphy and ultrasonography, patients
      underwent parathyroidectomy with intraoperative parathyroid hormone monitoring
      using a focused approach through a limited neck incision (DP) or bilateral neck
      exploration (BNE) through a standard collar incision. MAIN OUTCOME MEASURES:
      Extent of exploration, operative time, length of stay, morbidity, and cure.
      RESULTS: Directed parathyroidectomy was completed in 70 patients and BNE in 30.
      Bilateral neck exploration was performed as the initial procedure in 13 patients
      and following intraoperative conversion from attempted DP in 17. Indications for
      predetermined BNE were failed preoperative localization (n = 8) and concomitant
      thyroid disease that required operative treatment (n = 5). The need for
      predetermined BNE decreased as preoperative localization improved. Intraoperative
      factors that necessitated conversion to BNE included persistently elevated
      intraoperative parathyroid hormone levels that accurately predicted
      multiglandular disease (n = 6), incorrect localization (n = 5), and inadequate
      exposure (n = 6). Operative time and length of stay were less for DP compared
      with BNE patients (66 vs 165 minutes and 0.5 vs 1.6 days, respectively). One
      patient had a temporary vocal cord paresis. All patients were eucalcemic in
      follow-up (4 months to 3 years). CONCLUSIONS: With accurate preoperative
      localization and intraoperative parathyroid hormone monitoring, DP can be
      successfully completed in most patients with sporadic primary
      hyperparathyroidism. Patients benefit from DP, which reduces operative time and
      length of stay and facilitates rapid convalescence.

PMID- 12799331
TI  - Preoperative predictors of malignancy in pancreatic intraductal papillary
      mucinous neoplasms.
AB  - HYPOTHESIS: Malignant intraductal papillary mucinous neoplasms (IPMNs) can be
      predicted before surgery. DESIGN: Retrospective review of a prospectively
      collected database. SETTING: Academic, urban, tertiary care hospital. PATIENTS:
      Sixty-four consecutive patients with a pathological diagnosis of IPMN.
      INTERVENTIONS: All 64 patients underwent surgical intervention for IPMN between
      December 8, 1988, and October 16, 2002. MAIN OUTCOME MEASURES: Reliable
      predictors of malignancy. RESULTS: The 64 patients underwent 69 operations: 39
      pancreaticoduodenectomies, 18 distal pancreatectomies, 7 total pancreatectomies,
      4 neck and/or body pancreatectomies, and 1 cystgastrostomy with pancreatic
      biopsy. Twenty-three of 69 specimens were malignant-12 in situ (high-grade
      dysplasia) and 11 invasive. In a univariate analysis of 12 clinical signs or
      symptoms recorded, diabetes mellitus and jaundice showed a significant
      association with malignancy of IPMN. Of 24 serum chemistry studies, hematologic
      studies, and tumor marker analyses (in serum, bile, and pancreatic fluid),
      elevation of serum alkaline phosphatase and glucose levels showed correlation
      with malignancy. Computed tomography, ultrasound, and endoscopic retrograde
      cholangiopancreatography findings did not distinguish between benign and
      malignant tumors. Atypia on preoperative cytologic analysis was specific for
      malignancy (93%) but lacked the same degree of sensitivity (40% in situ, 91%
      invasive, and 67% overall). CONCLUSIONS: Malignancy of IPMNs is suggested by new
      onset diabetes mellitus, jaundice, and elevations in serum glucose or alkaline
      phosphatase levels. Atypia on preoperative cytologic testing is the finding most
      predictive of malignancy. The absence of these features does not predict benign
      disease. These findings may help guide patient and physician decision making.

PMID- 12799332
TI  - Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge
      stereotactic core needle biopsy.
AB  - BACKGROUND: Nonpalpable mammographic abnormalities are frequently evaluated by
      means of a stereotactic core needle biopsy. This technique is a very sensitive
      indicator of invasive cancer, but is less reliable to discriminate between ductal
      carcinoma in situ and atypical ductal hyperplasia (ADH). The objective of this
      study was to determine the correlation of the 11-gauge vacuum-assisted core
      needle biopsy to open biopsy when a diagnosis of ADH is obtained. HYPOTHESIS: The
      use of 11-gauge vacuum-assisted stereotactic core needle biopsy does not
      conclusively diagnose ADH. DESIGN: Retrospective analysis. SETTING: University
      affiliated teaching hospital. PATIENTS: Mammographic findings were evaluated with
      an 11-gauge vacuum-assisted stereotactic core biopsy in 1750 patients. Seventy
      seven patients were diagnosed as having ADH; of these, 65 underwent excisional
      biopsy. MAIN OUTCOME MEASURES: Pathological upstaging rate. RESULTS: Of the 65
      patients who underwent excisional breast biopsy, 11 (17%) had their condition
      upstaged to a breast cancer diagnosis. These patients had presented at a later
      age than those who retained a benign diagnosis after excisional biopsy. The
      number of cores taken did not correlate with diagnostic accuracy. CONCLUSIONS: Of
      the 65 patients who underwent open biopsy for ADH in this series, only 83% had an
      accurate diagnosis. A diagnosis of ADH by stereotactic core needle biopsy should
      be followed by an open excisional biopsy.

PMID- 12799333
TI  - Is combined partial hepatectomy with segmental resection of inferior vena cava
      justified for malignancy?
AB  - HYPOTHESIS: En bloc partial hepatectomy with inferior vena cava (IVC) resection
      may be the only curative strategy for patients with hepatic malignancies
      involving the IVC. DESIGN: Retrospective study. SETTING: Tertiary referral
      center. PATIENTS: All consecutive patients undergoing combined partial
      hepatectomy with segmental IVC resection and reconstruction between 1990 and
      2002. Patients with tangential excision of the IVC were excluded. Follow-up was
      completed by outpatient clinic visits and mail correspondence. MAIN OUTCOME
      MEASURES: Perioperative outcomes; overall and recurrence-free survival. RESULTS:
      Nineteen patients (7 men and 12 women) underwent partial hepatectomy and
      segmental IVC resection and reconstruction. Median age was 59 years (range, 24-74
      years). Diagnoses consisted of cholangiocarcinoma (9 patients), metastatic tumor
      (5 patients), sarcoma (3 patients), and hepatocellular carcinoma (2 patients).
      Major hepatectomies (>/=3 segments) were performed in 15 patients; the caudate
      lobe was resected in 13. Hepatic vascular isolation was used in 13 patients.
      Ringed polytef grafts were used for IVC reconstruction in all but 1 patient.
      Transfusion was necessary in 18 patients (median requirement, 5 U). Median
      operative time was 6.3 hours (range, 3.7-9.0 hours), and hospitalization was 10.5
      days (range, 6-41 days). Negative margins of resection were achieved in 16
      patients. Complications occurred in 8 patients (42%), including 1 perioperative
      death (5%). There was evidence of mural thrombosis of the graft in 2 patients
      (both nonocclusive); warfarin sodium was used postoperatively in 14. Late graft
      thrombosis was evident in 2 patients. Median overall survival was 38 months (5
      year survival, 21%), and recurrence-free survival was 11.5 months (5-year
      survival, 0%). CONCLUSIONS: Patients with large tumors involving both the liver
      and the IVC are candidates for partial hepatectomy and segmental IVC resection.
      Resection affords the possibility of negative margins, acceptable perioperative
      morbidity and mortality, long-term graft patency, and prolonged survival.

PMID- 12799334
TI  - Intraoperative parathyroid hormone assay: an accurate predictor of symptomatic
      hypocalcemia following thyroidectomy.
AB  - HYPOTHESIS: Intraoperative parathyroid hormone (IOPTH) assay is useful for
      predicting symptomatic hypocalcemia following total thyroidectomy. DESIGN: A
      prospective study of 30 patients undergoing total thyroidectomy with IOPTH levels
      obtained following skin closure and ionized calcium (Ca2+) levels obtained 6
      hours postoperatively and on postoperative day 1. All patients were evaluated for
      symptoms of hypocalcemia. SETTING: University teaching hospital. MAIN OUTCOME
      MEASURES: Patients who developed symptomatic hypocalcemia were compared with
      asymptomatic patients in regard to age, diagnosis, thyroid weight, thyrotropin
      level, Ca2+ level, parathyroid status, and IOPTH level. RESULTS: The onset of
      symptomatic hypocalcemia ranged from 8 to 48 hours postoperatively (n = 10). One
      patient required readmission. Of 10 patients with symptoms, 5 developed tetany.
      There were no significant differences in age, diagnosis, thyroid weight,
      thyrotropin level, or the number of parathyroid glands preserved in patients with
      or without symptomatic hypocalcemia. All patients with an IOPTH level of less
      than 10 pg/mL (1.1 pmol/L) had symptoms (n = 8). The mean +/- SD IOPTH level (7.6
      +/- 12.0 pg/mL [0.8 +/- 1.3 pmol/L]) in patients who developed symptomatic
      hypocalcemia was significantly lower than the mean IOPTH level (55.7 +/- 31.8
      pg/mL [5.9 +/- 3.3 pmol/L]) in patients without symptoms (P =.001). The 6-hour
      and postoperative day 1 Ca2+ levels were significantly lower in patients with
      symptomatic hypocalcemia (P =.19 and P =.13, respectively). An IOPTH level of
      less than 10 pg/mL is 80% sensitive and 100% specific for the development of
      symptomatic hypocalcemia. CONCLUSION: The incorporation of the IOPTH assay in the
      management of thyroid disease is recommended to prevent and prospectively treat
      symptomatic hypocalcemia, thereby reducing readmissions following thyroidectomy.

PMID- 12799335
TI  - Supranormal trauma resuscitation causes more cases of abdominal compartment
      syndrome.
AB  - HYPOTHESIS: Normal resuscitation (oxygen delivery index [DO2I] >/=500 mL/min per
      square meter), compared with supranormal trauma resuscitation (DO2I >/=600 mL/min
      per square meter), requires less crystalloid volume, thus decreasing the
      incidence of intra-abdominal hypertension (IAH) and abdominal compartment
      syndrome (ACS). DESIGN: Retrospective analysis of a prospective database.
      SETTING: Twenty-bed intensive care unit (ICU) in a regional level I trauma
      center. PATIENTS: Patients with major trauma (injury severity score >15, initial
      base deficit >/=6 mEq/L, or need for >/=6 units of packed red blood cells in the
      first 12 hours) or age 65 years or older with any 2 of the previous criteria.
      INTERVENTIONS: Shock/trauma resuscitation protocol: pulmonary artery catheter,
      gastric tonometry, urinary bladder pressure measurements, lactated Ringer
      infusion, packed red blood cell transfusion, and moderate inotrope support, as
      needed, in that sequence, to attain and maintain a DO2I greater than or equal to
      600 mL/min per m2 (16 months, ending January 1, 2001, n = 85) or a DO2I greater
      than or equal to 500 mL/min per square meter (16 months, starting January 1,
      2001, n = 71) for the first 24 hours in the ICU. MAIN OUTCOME MEASURES: Lactated
      Ringer infusion volume (liters) at ICU admission, gastric partial carbon dioxide
      minus end-tidal carbon dioxide(GAPCO2), IAH (urinary bladder pressure
      measurements >20 mm Hg), ACS (urinary bladder pressure measurements >25 mm Hg
      with organ dysfunction), multiple organ failure, and mortality. RESULTS:
      Demographics, injury severity, and shock severity parameters were similar in both
      groups. The supranormal resuscitation group required more lactated Ringer
      infusion volume in the first 24 hours in the ICU (mean +/- SD, 13 +/- 2 vs 7 +/-
      1 L; P<.05) and had higher GAPCO2 (16 +/- 2 vs 7 +/- 1 mm Hg; P<.05). In the
      supranormal group, IAH (42% vs 20%; P<.05) and ACS (16% vs 8%; P<.05) were more
      frequent. The conventional trauma outcomes, such as multiple organ failure (22%
      vs 9%; P<.05) and mortality (27% vs 11%; P<.05) were less favorable in the
      supranormal resuscitation group. CONCLUSION: Supranormal resuscitation, compared
      with normal resuscitation, was associated with more lactated Ringer infusion,
      decreased intestinal perfusion (higher GAPCO2), and an increased incidence of
      IAH, ACS, multiple organ failure, and death.

PMID- 12799336
TI  - Wall stent-enhanced lateral pancreaticojejunostomy for small-duct pancreatitis.
AB  - HYPOTHESIS: The purpose of this study was to see if a small (<7 mm) pancreatic
      duct could be dilated to an acceptable diameter, allowing lateral
      pancreaticojejunostomy to decompress the pancreatic duct and relieve pain, while
      preserving pancreatic endocrine and exocrine function. DESIGN: Patients with
      chronic pancreatitis who had a small main pancreatic duct underwent progressive
      trans-ampullary dilation of the duct and subsequent placement of an expandable
      metallic wall stent (wallstent; Boston Scientific Microvasive Division, Natick,
      Mass). Approximately 14 days later, a lateral pancreaticojejunostomy was done.
      SETTING: A 400-bed university referral center hospital in an urban setting.
      PATIENTS: Thirty-five patients were selected from a large group with chronic
      pancreatitis. Thirty-one had pancreas divisum. All patients had undergone
      transendoscopic sphincterotomies and stenting before being accepted into the
      study. All had endoscopic retrograde cholangiopancreatography-proven chronic
      pancreatitis, and all ducts were observed to be 7 mm or smaller. INTERVENTIONS:
      Patients were selected after endoscopic sphincterotomy and stenting failed.
      Progressive transendoscopic duct dilation with plastic stents was carried out,
      and a 10-mm expandable metallic wall stent was placed prior to surgical
      decompression. Lateral pancreaticojejunostomy was performed. MAIN OUTCOME
      MEASURES: Patients were observed for pain relief, postoperative symptoms,
      analgesic use, glucose intolerance, and quality of life. All patients were seen
      or contacted by telephone, and their results were recorded. RESULTS: There were
      no operative deaths, but 26% of patients had complications. Seventy-one percent
      of patients reported that their pain was better than preoperatively. Three
      patients had subsequent pancreatic surgery. No new cases of diabetes occurred
      except in the 2 patients who underwent total pancreatectomy. CONCLUSIONS: In
      general, most patients feel that their lives were improved by the procedure. A
      quarter of the patients no longer take narcotics, and many have been able to
      resume a relatively normal lifestyle. Although this procedure is not a panacea
      for all patients with chronic pancreatitis and a nondilated duct, it is a
      reasonable alternative to resection.

PMID- 12799337
TI  - Morphologic changes and outcome following endovascular abdominal aortic aneurysm
      repair as a function of aneurysm size.
AB  - HYPOTHESIS: Small infrarenal abdominal aortic aneurysms have a more favorable
      clinical and morphologic outcome compared with medium and large abdominal aortic
      aneurysms following endovascular aneurysm repair(EVAR). DESIGN: A prospective
      clinical series of 206 patients undergoing elective EVAR between 1996 and 2001.
      SETTING: A tertiary care academic health center. PATIENTS: Patients were grouped
      according to aneurysm size: small (<50 mm), medium (50-60 mm), and large (>60
      mm). INTERVENTIONS: Primary EVAR and secondary procedures to secure fixation of
      the stent graft and surgical conversions. MAIN OUTCOME MEASURES: Aneurysm
      diameter, endoleaks, and long-term morphologic changes were analyzed
      postoperatively with 3-dimensional reconstructions of computed tomographic
      angiograms. RESULTS: Groups were similar in age, comorbidities, and follow-up
      (mean +/- SD, 32.1 +/- 11.8 months). There were 30 small aneurysms, 92 medium
      aneurysms, and 84 large aneurysms, with a mean size of 45.1 +/- 3.7 mm, 53.8 +/-
      3.1 mm, and 66.1 +/- 6.8 mm, respectively (P<.01). There was no significant
      difference in proximal neck or iliac artery diameter among the 3 groups. The
      proximal aortic neck length (28.1 +/- 11.6 mm [small]; 23.9 +/- 11.3 mm [medium];
      and 22.1 +/- 11.6 mm [large]; P<.05) was significantly shorter in large
      aneurysms. Furthermore, there was a significant increase (6% [small]; 15%
      [medium]; and 21% [large]; P<.05) in angulated necks in large aneurysms.
      Following treatment, aneurysm diameter remained stable in most patients (83%
      [small]; 82% [medium]; and 83% [large]), with a mean decrease of 2.0 +/- 6.5 mm,
      2.1 +/- 6.1 mm, and 3.7 +/- 7.7 mm in each group, respectively (P =.45). There
      was no difference in the incidence of endoleaks, aneurysm contraction, or
      aneurysm expansion based on preoperative aneurysm diameter. Secondary procedures
      were performed in 5 (20%) of 25, 9 (5.2%) of 170, and 5 (36%) of 11 aneurysms
      that contracted, remained stable, or expanded, respectively, following EVAR
      (P<.05). CONCLUSIONS: There is a 15% increase in neck angulation and a 27%
      decrease in neck length in large compared with small infrarenal abdominal aortic
      aneurysms, with no difference in outcome. Aneurysms that are stable following
      EVAR have a significantly lower incidence of requiring secondary procedures.

PMID- 12799338
TI  - Spectrum of cystic neoplasms of the pancreas and their surgical management.
AB  - BACKGROUND: Owing to increased awareness and the widespread use of abdominal
      ultrasonography and computed tomography, an increasing number of cystic neoplasms
      are being identified. Cystic neoplasms of the pancreas are divided into the
      following 4 main groups: serous cystic neoplasms, mucinous cystic neoplasms,
      solid pseudopapillary neoplasms, and intraductal pancreatic mucinous neoplasms.
      OBJECTIVE: To review our experience with cystic neoplasms of the pancreas at our
      institution from January 1992 through September 2002. METHODS: Medical records
      were reviewed for age, sex, clinical signs and symptoms, diagnosis, surgical
      treatment, morbidity, mortality, and histologic features. RESULTS: Seventy-three
      patients (49 women and 24 men) underwent surgical resection of a cystic neoplasm
      of the pancreas from January 1992 through September 2002. The most common
      presenting symptom was abdominal pain. Other symptoms included nausea, emesis,
      weight loss, jaundice, and pancreatitis. Most patients (73%) had no
      complications. The most common complication (10%) was pancreatic fistula. There
      were 3 deaths. CONCLUSIONS: Cystic neoplasms of the pancreas are an increasing
      entity. Long-term survival of patients with these tumors is generally better than
      that of patients with adenocarcinoma of the pancreas and mandates aggressive
      resectional therapy in most patients. Resection of these tumors can be done with
      resultant low morbidity and mortality rates.

PMID- 12799339
TI  - A survey of residents and faculty regarding work hour limitations in surgical
      training programs.
AB  - HYPOTHESIS: Surgical faculty and residents have significantly different attitudes
      regarding work hour restrictions. SETTING: All general surgery residencies
      approved by the Accreditation Council for Graduate Medical Education (ACGME).
      PARTICIPANTS: All voluntarily participating surgical faculty and residents. MAIN
      OUTCOME MEASURES: Current hours worked, days off per month, and attitudes and
      opinions regarding the current surgical-training environment. METHODS: A 17
      question survey instrument was mailed to the program directors of all ACGME
      approved surgical-training programs in the United States. They were requested to
      distribute the survey to all faculty and residents for completion and to return
      the forms for analysis. RESULTS: Responses (N = 1653) were received from 46% of
      surgical-training programs. A significant difference was noted between faculty
      and resident responses in most categories. Most residents (87%) reported more
      than 80 duty hours per week, whereas 45% reported working more than 100 hours per
      week. Only 30% of residents reported an average of 1 day per week free of
      clinical activities. Although a minority of residents (43%) felt that their
      workload was excessive, 57% felt that their cognitive abilities had been impaired
      by fatigue. A significant number of residents (64%) and faculty (39%) believe
      that duty hour restrictions should be adopted. A minority of residents (20%) and
      faculty (47%) believe that the duration of residency training should be increased
      to compensate for duty hour restrictions. One quarter of residents regret
      choosing a career in surgery. CONCLUSIONS: Current duty hours for most surgical
      residents exceed the proposed ACGME limits. Although most residents support duty
      hour limits; surgical faculty are less supportive. Significant alterations in the
      current design and structure of surgical-training programs will be required to
      meet the ACGME guidelines.

PMID- 12799340
TI  - Competencies.

PMID- 12799341
TI  - Image of the month. Acute intussusception.

PMID- 12799342
TI  - Analysis of the two active sites of the hyaluronan synthase and the chondroitin
      synthase of Pasteurella multocida.
AB  - Type A Pasteurella multocida produces a hyaluronan (HA) capsule to enhance
      infection. The 972-residue HA synthase, pmHAS, polymerizes the linear HA
      polysaccharide composed of alternating beta3N-acetylglucosamine (GlcNAc)
      beta4glucuronic acid (GlcUA). We demonstrated previously that pmHAS possesses two
      independent glycosyltransferase sites. Here we further define the sites and
      putative motifs. Deletion of residues 1-117 does not affect HA polymerizing
      activity. The carboxyl-terminal boundary of the GlcUA-transferase resides within
      residues 686-703. Both transferase sites contain a DXD motif essential for HA
      synthase activity. D247N or D249N mutants possessed only GlcUA-transferase
      activity, whereas D527N or D529N mutants possessed only GlcNAc-transferase
      activity, further confirming our assignment of the two active sites within the
      synthase polypeptide. A potential role of the DXD motif in substrate binding was
      supported by experiments utilizing high UDP-sugar concentrations that partially
      rescued the activity of certain mutants. The WGGED sequence motif is involved in
      GlcNAc-transferase activity because mutants with substitutions at E369 or D370
      possessed only GlcUA-transferase activity. Type F P. multocida synthesizes an
      unsulfated chondroitin (beta3GalNAc-beta4GlcUA) capsule. A chimeric enzyme
      consisting of residues 1-427 of pmHAS and residues 421-704 of pmCS, the
      homologous chondroitin synthase, was an active HA synthase. The converse chimeric
      enzyme consisting of residues 1-420 of pmCS and residues 428-703 of pmHAS was a
      functional chondroitin synthase. Analyses of a panel of pmHAS/pmCS chimeric
      enzymes identified a 44-residue region, corresponding to pmHAS residues 225-265,
      involved in UDP-hexosamine selectivity. Overall, these findings further support
      the model of two independent transferase sites within a single polypeptide.

PMID- 12799343
TI  - Structural investigation of chondroitin/dermatan sulfate oligosaccharides from
      human skin fibroblast decorin.
AB  - Hybrid chondroitin/dermatan sulfate (CS/DS) glycosaminoglycan chains, derived
      from decorin secreted by human skin fibroblasts, were shown to interact with FGF
      2, as did oligosaccharides derived therefrom by chondroitin B lyase digestion. In
      a first attempt to identify the biologically active sequence, a novel protocol
      for structural analysis of enzyme-resistant oligosaccharides larger than standard
      trisulfated hexasaccharides was developed. The method bases on capillary
      electrophoresis (CE) for separating oversulfated species in offline combination
      with nanoelectrospray ionization quadrupole time-of-flight tandem mass
      spectrometry (nanoESI-QTOF-MS/MS) in the negative ion mode. Under optimized CE
      and ESI-MS conditions, up to 12-mer oligosaccharides with different degrees of
      sulfation were identified. A novel tandem MS protocol (CID-VE) was applied to
      elucidate the structure of a previously undescribed pentasulfated CS/DS
      hexasaccharide, Delta-4,5-IdoAGalNAc[GlcAGalNAc]2(5S). In this molecular species,
      detected as a triply charged ion at m/z 511.38, three sulfates are found in the
      IdoAGalNAcGlcA moiety offering two structural variants: one containing sulfated
      IdoA together with a disulfated GalNAc moiety and in the other one both uronic
      acids, that is, GlcA and IdoA and the amino sugar each carry a sulfate ester
      group.

PMID- 12799344
TI  - Cloning of a rat gene encoding the histo-blood group B enzyme: rats have more
      than one Abo gene.
AB  - A genomic DNA fragment corresponding to exon 7 of the human ABO gene was
      amplified from rats of several inbred and outbred strains. Five different
      sequences were obtained, four of them corresponding to A-type sequences and one
      to a B-type sequence based on the amino acids equivalent to residues at positions
      266 and 268 of the human enzymes. In rats from inbred strains, a single A-type
      sequence and the unique B-type sequence were found, whereas some animals of
      outbred strains presented two or three A-type sequences along with the B-type
      sequence. The complete coding sequence of the B-type gene was obtained;
      identification of the exon-intron boundaries, determined by comparison with rat
      genomic sequences from data banks, revealed that the rat B-type gene structure is
      identical with that of the mouse Abo gene. Compared with the human ABO gene and
      the rat A gene, it lacks exon 4. Like the rat A gene (symbol: Abo), the rat B
      gene (symbol: Abo2) is located on chromosome 3q11-q12. It could be shown by
      transfection experiments that the B-type cDNA encodes an active B transferase. A
      transcript of the B gene was found ubiquitously, whereas the B antigen was only
      detected in a restricted set of tissues. These data indicate that rats have at
      least two distinct Abo genes, one monomorphic gene encoding a B-specific enzyme
      and one or more genes in some cases encoding an A-specific enzyme.

PMID- 12799345
TI  - Genome sequence of an M3 strain of Streptococcus pyogenes reveals a large-scale
      genomic rearrangement in invasive strains and new insights into phage evolution.
AB  - Group Astreptococcus (GAS) is a gram-positive bacterial pathogen that causes
      various suppurative infections and nonsuppurative sequelae. Since the late 1980s,
      streptococcal toxic-shock like syndrome (STSS) and severe invasive GAS infections
      have been reported globally. Here we sequenced the genome of serotype M3 strain
      SSI-1, isolated from an STSS patient in Japan, and compared it with those of
      other GAS strains. The SSI-1 genome is composed of 1,884,275 bp, and 1.7 Mb of
      the sequence is highly conserved relative to strain SF370 (serotype M1) and
      MGAS8232 (serotype M18), and almost completely conserved relative to strain
      MGAS315 (serotype M3). However, a large genomic rearrangement has been shown to
      occur across the replication axis between the homologous rrn-comX1 regions and
      between two prophage-coding regions across the replication axis. Atotal of 1 Mb
      of chromosomal DNA is inverted across the replication axis. Interestingly, the
      recombinations between the prophage regions are within the phage genes, and the
      genes encoding superantigens and mitogenic factors are interchanged between two
      prophages. This genomic rearrangement occurs in 65% of clinical isolates (64/94)
      collected after 1990, whereas it is found in only 25% of clinical isolates (7/28)
      collected before 1985. These observations indicate that streptococcal phages
      represent important plasticity regions in the GAS chromosome where recombination
      between homologous phage genes can occur and result not only in new phage
      derivatives, but also in large chromosomal rearrangements.

PMID- 12799347
TI  - The zebrafish annexin gene family.
AB  - The Annexins (ANXs) are a family of calcium- and phospholipid-binding proteins
      that have been implicated in many cellular processes, including channel
      formation, membrane fusion, vesicle transport, and regulation of phospholipase A2
      activity. As a first step toward understanding in vivo function, we have cloned
      11 zebrafish anx genes. Four genes (anx1a, anx2a, anx5,and anx11a) were
      identified by screening a zebrafish cDNA library with a Xenopus anx2 fragment.
      For these genes, full-length cDNA sequences were used to cluster 212 EST
      sequences generated by the Zebrafish Genome Resources Project. The EST analysis
      revealed seven additional anx genes that were subsequently cloned. The genetic
      map positions of all 11 genes were determined by using a zebrafish radiation
      hybrid panel. Sequence and syntenic relationships between zebrafish and human
      genes indicate that the 11 genes represent orthologs of human
      anx1,2,4,5,6,11,13,and suggest that several zebrafish anx genes resulted from
      duplications that arose after divergence of the zebrafish and mammalian genomes.
      Zebrafish anx genes are expressed in a wide range of tissues during embryonic and
      larval stages. Analysis of the expression patterns of duplicated genes revealed
      both redundancy and divergence, with the most similar genes having almost
      identical tissue-specific patterns of expression and with less similar duplicates
      showing no overlap. The differences in gene expression of recently duplicated anx
      genes could explain why highly related paralogs were maintained in the genome and
      did not rapidly become pseudogenes.

PMID- 12799349
TI  - Extrachromosomal circular DNA of tandemly repeated genomic sequences in
      Drosophila.
AB  - One characteristic of genomic plasticity is the presence of extrachromosomal
      circular DNA (eccDNA). This DNA is found in various eukaryotes from yeast to
      humans, and its levels are elevated by exposure to carcinogens. eccDNA is
      heterogeneous in size and composed of chromosomal sequences. In this study we
      used two-dimensional gel electrophoresis to detect and characterize eccDNA in
      Drosophila. We found eccDNA throughout the fly's life cycle. These molecules
      comprise up to 10% of the total repetitive DNA content, and their size ranges
      from <1 kb to >20 kb. The eccDNA population contains circular multimers of
      tandemly repeated genes such as histones, rDNA, Stellate, and the Suppressor of
      Stellate. Multimers of centromeric heterochromatin sequences are included in
      eccDNA as well. Our findings are consistent with the hypothesis that
      intramolecular homologous recombination between direct tandem repeats is a
      favorite mechanism for eccDNA formation. The level of eccDNA increased following
      MMS treatment of wild-type larvae, consistent with phenomena observed in cultured
      mammalian cells. This shows mutagen-induced eccDNA formation in the context of
      the whole organism for the first time. Mutations in the genes okra, mus309, and
      mei41 did not affect eccDNA under normal conditions or following mutagen
      treatment, implying that eccDNA formation is different from known pathways of DNA
      repair.

PMID- 12799348
TI  - Evolutionary conservation of regulatory elements in vertebrate Hox gene clusters.
AB  - Comparisons of DNA sequences among evolutionarily distantly related genomes
      permit identification of conserved functional regions in noncoding DNA. Hox genes
      are highly conserved in vertebrates, occur in clusters, and are uninterrupted by
      other genes. We aligned (PipMaker) the nucleotide sequences of the HoxA clusters
      of tilapia, pufferfish, striped bass, zebrafish, horn shark, human, and mouse,
      which are separated by approximately 500 million years of evolution. In support
      of our approach, several identified putative regulatory elements known to
      regulate the expression of Hox genes were recovered. The majority of the newly
      identified putative regulatory elements contain short fragments that are almost
      completely conserved and are identical to known binding sites for regulatory
      proteins (Transfac database). The regulatory intergenic regions located between
      the genes that are expressed most anteriorly in the embryo are longer and
      apparently more evolutionarily conserved than those at the other end of Hox
      clusters. Different presumed regulatory sequences are retained in either the
      Aalpha or Abeta duplicated Hox clusters in the fish lineages. This suggests that
      the conserved elements are involved in different gene regulatory networks and
      supports the duplication-deletion-complementation model of functional divergence
      of duplicated genes.

PMID- 12799346
TI  - New evidence for genome-wide duplications at the origin of vertebrates using an
      amphioxus gene set and completed animal genomes.
AB  - The 2R hypothesis predicting two genome duplications at the origin of vertebrates
      is highly controversial. Studies published so far include limited sequence data
      from organisms close to the hypothesized genome duplications. Through the
      comparison of a gene catalog from amphioxus, the closest living invertebrate
      relative of vertebrates, to 3453 single-copy genes orthologous between
      Caenorhabditis elegans (C), Drosophila melanogaster (D), and Saccharomyces
      cerevisiae (Y), and to Ciona intestinalis ESTs, mouse, and human genes, we show
      with a large number of genes that the gene duplication activity is significantly
      higher after the separation of amphioxus and the vertebrate lineages, which we
      estimate at 650 million years (Myr). The majority of human orthologs of 195 CDY
      groups that could be dated by the molecular clock appear to be duplicated between
      300 and 680 Myr with a mean at 488 million years ago (Mya). We detected 485
      duplicated chromosomal segments in the human genome containing CDY orthologs, 331
      of which are found duplicated in the mouse genome and within regions syntenic
      between human and mouse, indicating that these were generated earlier than the
      human-mouse split. Model based calculations of the codon substitution rate of the
      human genes included in these segments agree with the molecular clock duplication
      time-scale prediction. Our results favor at least one large duplication event at
      the origin of vertebrates, followed by smaller scale duplication closer to the
      bird-mammalian split.

PMID- 12799350
TI  - Multimeric threading-based prediction of protein-protein interactions on a
      genomic scale: application to the Saccharomyces cerevisiae proteome.
AB  - MULTIPROSPECTOR, a multimeric threading algorithm for the prediction of protein
      protein interactions, is applied to the genome of Saccharomyces cerevisiae. Each
      possible pairwise interaction among more than 6000 encoded proteins is evaluated
      against a dimer database of 768 complex structures by using a confidence estimate
      of the fold assignment and the magnitude of the statistical interfacial
      potentials. In total, 7321 interactions between pairs of different proteins are
      predicted, based on 304 complex structures. Quality estimation based on the
      coincidence of subcellular localizations and biological functions of the
      predicted interactors shows that our approach ranks third when compared with all
      other large-scale methods. Unlike other in silico methods, MULTIPROSPECTOR is
      able to identify the residues that participate directly in the interaction. Three
      hundred seventy-four of our predictions can be found by at least one of the other
      studies, which is compatible with the overlap between two different other
      methods. From the analysis of the mRNA abundance data, our method does not bias
      towards proteins with high abundance. Finally, several relevant predictions
      involved in various functions are presented. In summary, we provide a novel
      approach to predict protein-protein interactions on a genomic scale that is a
      useful complement to experimental methods.

PMID- 12799351
TI  - The pattern of polymorphism on human chromosome 21.
AB  - Polymorphism data from 20 partially resequenced copies of human chromosome 21
      more than 20,000 polymorphic sites-were analyzed. The allele-frequency
      distribution shows no deviation from the simplest population genetic model with a
      constant population size (although we show that our analysis has no power to
      detect population growth). The average rate of recombination per site is
      estimated to be roughly one-half of the rate of mutation per site, again in
      agreement with simple model predictions. However, sliding-window analyses of the
      amount of polymorphism and the extent of linkage disequilibrium (LD) show
      significant deviations from standard models. This could be due to the history of
      selection or demographic change, but it is impossible to draw strong conclusions
      without much better knowledge of variation in the relationship between genetic
      and physical distance along the chromosome.

PMID- 12799353
TI  - Computational discovery of internal micro-exons.
AB  - Very short exons, also known as micro-exons, occur in large numbers in some
      eukaryotic genomes. Existing annotation tools have a limited ability to recognize
      these short sequences, which range in length up to 25 bp. Here, we describe a
      computational method for the identification of micro-exons using near-perfect
      alignments between cDNA and genomic DNA sequences. Using this method, we detected
      319 micro-exons in 4 complete genomes, of which 224 were previously unknown,
      human (170), the nematode Caenorhabditis elegans (4), the fruit fly Drosophila
      melanogaster (14), and the mustard plant Arabidopsis thaliana (36). Comparison of
      our computational method with popular cDNA alignment programs shows that the new
      algorithm is both efficient and accurate. The algorithm also aids in the
      discovery of micro-exon-skipping events and cross-species micro-exon
      conservation.

PMID- 12799354
TI  - eVOC: a controlled vocabulary for unifying gene expression data.
AB  - Expression data contribute significantly to the biological value of the sequenced
      human genome, providing extensive information about gene structure and the
      pattern of gene expression. ESTs, together with SAGE libraries and microarray
      experiment information, provide a broad and rich view of the transcriptome.
      However, it is difficult to perform large-scale expression mining of the data
      generated by these diverse experimental approaches. Not only is the data stored
      in disparate locations, but there is frequent ambiguity in the meaning of terms
      used to describe the source of the material used in the experiment. Untangling
      semantic differences between the data provided by different resources is
      therefore largely reliant on the domain knowledge of a human expert. We present
      here eVOC, a system which associates labelled target cDNAs for microarray
      experiments, or cDNA libraries and their associated transcripts with controlled
      terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal
      controlled vocabularies suitable for describing the domains of human gene
      expression data including Anatomical System, Cell Type, Pathology and
      Developmental Stage. We have curated and annotated 7016 cDNA libraries
      represented in dbEST, as well as 104 SAGE libraries,with expression
      information,and provide this as an integrated, public resource that allows the
      linking of transcripts and libraries with expression terms. Both the vocabularies
      and the vocabulary-annotated libraries can be retrieved from
      http://www.sanbi.ac.za/evoc/. Several groups are involved in developing this
      resource with the aim of unifying transcript expression information.

PMID- 12799352
TI  - Genome analysis of F. nucleatum sub spp vincentii and its comparison with the
      genome of F. nucleatum ATCC 25586.
AB  - We present the draft genome sequence and its analysis for Fusobacterium nucleatum
      sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586
      (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have
      been identified. Of these, 118 ORFs have no known function and are unique to FNV,
      whereas 323 ORFs have functional orthologs in other organisms. In addition to the
      excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability
      to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate
      galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to
      transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic
      type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase
      Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages,
      and three types of restriction-modification systems have been identified in FNV.
      ORFs for ethanolamine utilization, thermostable carboxypeptidase, gamma glutamyl
      transpeptidase, and deblocking aminopeptidases are absent from FNV. FNV, like FN,
      lacks the classical catalase-peroxidase system, but thioredoxin/glutaredoxin
      enzymes might alleviate oxidative stress. Genes for resistance to antibiotics
      such as acriflavin, bacitracin, bleomycin, daunorubicin, florfenicol, and other
      general multidrug resistance are present. These capabilities allow Fusobacteria
      to survive in a mixed culture in the mouth.

PMID- 12799355
TI  - Kinase pathway database: an integrated protein-kinase and NLP-based protein
      interaction resource.
AB  - Protein kinases play a crucial role in the regulation of cellular functions.
      Various kinds of information about these molecules are important for
      understanding signaling pathways and organism characteristics. We have developed
      the Kinase Pathway Database, an integrated database involving major completely
      sequenced eukaryotes. It contains the classification of protein kinases and their
      functional conservation, ortholog tables among species, protein-protein, protein
      gene, and protein-compound interaction data, domain information, and structural
      information. It also provides an automatic pathway graphic image interface. The
      protein, gene, and compound interactions are automatically extracted from
      abstracts for all genes and proteins by natural-language processing (NLP). The
      method of automatic extraction uses phrase patterns and the GENA protein, gene,
      and compound name dictionary, which was developed by our group. With this
      database, pathways are easily compared among species using data with more than
      47,000 protein interactions and protein kinase ortholog tables. The database is
      available for querying and browsing at http://kinasedb.ontology.ims.u
      tokyo.ac.jp/.

PMID- 12799356
TI  - Internet Contig Explorer (iCE)--a tool for visualizing clone fingerprint maps.
AB  - Fingerprinted clone physical maps have proven useful in various applications,
      supporting both whole-genome and region-specific DNA sequencing as well as gene
      cloning studies. Fingerprint maps have been generated for several genomes,
      including those of human, mouse, rat, the nematodes Caenorhabditis elegans and
      Caenorhabditis briggsae, Arabidopsis thaliana and rice. Fingerprint maps of other
      genomes, including those of fungi, bacteria, poplar, and the cow, are being
      generated. The increasing use of fingerprint maps in genomic research has spawned
      a need in the research community for intuitive computer tools that facilitate
      viewing of the maps and the underlying fingerprint data. In this report we
      describe a new Java-based application called iCE (Internet Contig Explorer) that
      has been designed to provide views of fingerprint maps and associated data. Users
      can search for and display individual clones, contigs, clone fingerprints, clone
      insert sizes and markers. Users can also load into the software lists of
      particular clones of interest and view their fingerprints. iCE is being used at
      our Genome Centre to offer up to the research community views of the mouse, rat,
      bovine, C. briggsae, and several fungal genome bacterial artificial chromosome
      (BAC) fingerprint maps we have either completed or are currently constructing. We
      are also using iCE as part of the Rat Genome Sequencing Project to manage our
      provision of rat BAC clones for sequencing at the Human Genome Sequencing Center
      at the Baylor College of Medicine.

PMID- 12799358
TI  - Curariform antagonists bind in different orientations to the nicotinic receptor
      ligand binding domain.
AB  - Curariform alkaloids competitively inhibit muscle acetylcholine receptors (AChR)
      by bridging the alpha and non-alpha subunits that form the ligand-binding site.
      Here we delineate bound orientations of d-tubocurarine (d-TC) and its methylated
      derivative metocurine using mutagenesis, ligand binding measurements, and
      computational methods. When tested against a series of lysine mutations in the
      epsilon subunit, the two antagonists show marked differences in the consequences
      of the mutations on binding affinity. The mutations epsilon L117K, epsilon Y111K,
      and epsilon L109K decrease affinity of metocurine by up to 3 orders of magnitude
      but only slightly alter affinity of d-TC. At the alpha subunit face of the
      binding site, the mutation alpha Y198T decreases affinity of both antagonists,
      but alpha Y198F preferentially enhances affinity of d-TC. Computation of
      antagonist docking orientations, based on our structural model of the alpha
      epsilon site of the human AChR, indicates distinct orientations of each
      antagonist; the flatter metocurine fits into a pocket formed principally by the
      epsilon subunit, whereas the more compact d-TC spans the narrower crevasse
      between alpha and epsilon subunits. The side chains of epsilon Tyr-111 and
      epsilon Thr-117 juxtapose one of two quaternary nitrogens in metocurine but are
      remote from the equivalent quaternary nitrogen in d-TC, which instead closely
      approaches alpha Tyr-198. The different docked orientations arise through tilt of
      the curariform scaffold by approximately 60 degrees normal to the nitrogen
      nitrogen axis, together with a 20 degrees rotation about the axis. The overall
      mutagenesis and computational results show that despite their similar structures,
      d-TC and metocurine bind in distinctly different orientations to the adult human
      AChR.

PMID- 12799359
TI  - Synergistic activation of endothelial nitric-oxide synthase (eNOS) by HSP90 and
      Akt: calcium-independent eNOS activation involves formation of an HSP90-Akt-CaM
      bound eNOS complex.
AB  - Endothelial nitric-oxide synthase (eNOS), which generates the endogenous
      vasodilator, nitric oxide (NO), is highly regulated by post-translational
      modifications and protein interactions. We recently used purified proteins to
      characterize the mechanisms by which heat shock protein 90 (HSP90) increases eNOS
      activity at low and high Ca2+ levels (Takahashi, S. and Mendelsohn, M. E. (2003)
      J. Biol. Chem. 278, 9339-9344). Here we extend these studies to explore
      interactions between HSP90, Akt, and eNOS. In studies with purified proteins,
      HSP90 increased the initial rate and maximal extent of Akt-mediated eNOS
      phosphorylation and activation at low Ca2+ levels. Akt was not observed in the
      eNOS complex in the absence of HSP90, but both active and inactive Akt associated
      with eNOS in the presence of HSP90. Direct binding of Akt to HSP90 was observed
      even in the absence of eNOS. HSP90 also facilitated CaM binding to eNOS
      irrespective of Akt presence. Geldanamycin (GA) disrupted HSP90-eNOS binding,
      reduced HSP90-stimulated CaM binding, and blocked both recruitment of Akt to the
      eNOS complex and phosphorylation of eNOS at Ser-1179. Akt phosphorylated only CaM
      bound eNOS, in an HSP90-independent manner. HSP90 and active Akt together
      increased eNOS activity synergistically, which was reversed by GA. In bovine
      aortic endothelial cells (BAECs), the effects of vascular endothelial growth
      factor (VEGF) and insulin on eNOS-HSP90-Akt complex formation and eNOS activation
      were compared. BAPTA-AM inhibited VEGF- but not insulin-induced eNOS-HSP90-Akt
      complex formation and eNOS phosphorylation. Insulin caused rapid, transient
      increase in eNOS activity correlated temporally with the formation of eNOS-HSP90
      Akt complex. GA prevented insulin-induced association of HSP90, Akt and CaM with
      eNOS and inhibited eNOS activation in BAECs. Both platelet-derived growth factor
      (PDGF) and insulin induced activation of Akt in BAECs, but only insulin caused
      HSP90-Akt-eNOS association and eNOS phosphorylation. These results demonstrate
      that HSP90 and Akt synergistically activate eNOS and suggest that this synergy
      contributes to Ca2+-independent eNOS activation in response to insulin.

PMID- 12799360
TI  - Correlation between alterations of the penicillin-binding protein 2 and
      modifications of the peptidoglycan structure in Neisseria meningitidis with
      reduced susceptibility to penicillin G.
AB  - Reduced susceptibility to penicillin G in Neisseria meningitidis is directly
      correlated with alterations in the penA gene, which encodes the penicillin
      binding protein 2 (PBP2). Using purified PBP2s from different backgrounds, we
      confirmed that the reduced susceptibility to penicillin G is associated with a
      decreased affinity of altered PBP2s for penicillin G. Infrared spectroscopy
      analysis using isogenic penicillin-susceptible strains and strains with reduced
      susceptibility to penicillin G suggested that the meningococcal cell wall is also
      modified in a penA-dependent manner. Moreover, reverse-phase high pressure liquid
      chromatography and mass spectrometry analysis of these meningococcal strains
      confirmed the modifications of peptidoglycan components and showed an increase in
      the peaks corresponding to pentapeptide-containing muropeptides. These results
      suggest that the D,D-transpeptidase and/or D,D-carboxypeptidase activities of
      PBP2 are modified by the changes in penA gene.

PMID- 12799361
TI  - Detailed structural analysis of the peptidoglycan of the human pathogen Neisseria
      meningitidis.
AB  - We used reverse-phase high pressure liquid chromatography (HPLC), matrix-assisted
      laser desorption ionization mass spectrometry (MALDI-MS) and post source decay
      analysis (MALDI-PSD) to determine the muropeptide composition of the human
      pathogen Neisseria meningitidis. Structural assignment was determined for 28
      muropeptide species isolated after HPLC separation and purification. Fourteen of
      these muropeptides were O-acetylated to different degrees. We identified the
      entire O-acetylation spectrum of dimers and trimers both in muropeptides and 1,6
      anhydromuropeptides. On average, one of three disaccharides was O-acetylated.
      Furthermore, the degree of cross-linking of the N. meningitidis peptidoglycan was
      around 39% in all the strains analyzed. MALDI-PSD analysis of several muropeptide
      species indicated that meningococci only synthesize D-alanyl-meso-diaminopimelate
      cross-bridges. No muropeptides representative of covalent linkages of
      lipoproteins to the peptidoglycan could be identified, unlike in Escherichia
      coli. Finally, comparison of the muropeptide composition of penicillin
      susceptible and penicillin-intermediate clinical strains of meningococci showed a
      positive correlation between the minimum inhibitory concentration (MIC) of
      penicillin G and the amount of muropeptides carrying an intact pentapeptide chain
      in the peptidoglycan. This suggests that reduced susceptibility to penicillin G
      in N. meningitidis is associated with a decrease in d,d-carboxypeptidase activity
      and/or D,D-transpeptidase activity.

PMID- 12799363
TI  - Functional correlates of mutations in beta-catenin exon 3 phosphorylation sites.
AB  - beta-Catenin-mediated signaling can be constitutively activated by truncation or
      mutation of serine and threonine residues in exon 3. Mutations in this region are
      observed in many human tumors. Examination of the locations of these mutations
      reveals interesting patterns; specifically, Ser45 and Thr41 appear more
      frequently in malignant tumors, and Ser37 and Ser33 are more common in benign
      entities. To test whether these patterns represent functional differences in beta
      catenin signaling mechanisms, we generated mutations of each of these residues.
      Stable transformation of Madin-Darby canine kidney cells showed a transformed
      phenotype with each of the four mutations, as assessed by growth in soft agar and
      collagen. Functional assays including proliferation assays, cell shedding assays,
      and wounding assays demonstrated two groups. Ser45 and Thr41 represent a more
      transformed phenotype, whereas Ser37 and Ser33 behaved similarly to the vector in
      these assays. Assessment of downstream genes demonstrated increased activation of
      the beta-catenin target gene cyclin D1 by Ser45. Finally, we examined the kinase
      activity of I kappa B kinase-alpha and found that this kinase, unlike glycogen
      synthase kinase-3 beta, appears to preferentially phosphorylate Ser45 and Thr41,
      independent of priming by casein kinase-1. We conclude that these sites may
      represent an alternative (non-wnt) signaling pathway, which may be
      inappropriately activated in tumors with mutations of these residues.

PMID- 12799362
TI  - Soluble branched beta-(1,4)glucans from Acetobacter species show strong
      activities to induce interleukin-12 in vitro and inhibit T-helper 2 cellular
      response with immunoglobulin E production in vivo.
AB  - An extracellular polysaccharide, AC-1, produced by Acetobacter polysaccharogenes
      is composed of beta-(1,4)glucan with branches of glucosyl residues. We found that
      AC-1 showed a strong activity to induce production of interleukin-12 P40 and
      tumor necrosis factor-alpha by macrophage cell lines in vitro. Cellulase
      treatment completely abolished the activity of AC-1 to induce tumor necrosis
      factor-alpha production by macrophages, whereas treatment of AC-1 with polymyxin
      B or proteinase did not affect the activity. Results of experiments using toll
      like receptor (TLR) 4-deficient mice and TLR4-transfected human cell line
      indicated that TLR4 is involved in pattern recognition of AC-1. In vivo
      administration of AC-1 significantly reduced the serum levels of ovalbumin (OVA)
      specific IgE and interleukin-4 production by T cells in response to OVA in mice
      immunized with OVA. AC-1, a soluble branched beta-(1,4)glucan may be useful in
      prevention and treatment of allergic disorders With IgE production.

PMID- 12799357
TI  - Large-scale identification and analysis of genome-wide single-nucleotide
      polymorphisms for mapping in Arabidopsis thaliana.
AB  - Genetic markers such as single nucleotide polymorphisms (SNPs) are essential
      tools for positional cloning, association, or quantitative trait locus mapping
      and the determination of genetic relationships between individuals. We identified
      and characterized a genome-wide set of SNP markers by generating 10,706 expressed
      sequence tags (ESTs) from cDNA libraries derived from 6 different accessions, and
      by analysis of 606 sequence tagged sites (STS) from up to 12 accessions of the
      model flowering plant Arabidopsis thaliana. The cDNA libraries for EST sequencing
      were made from individuals that were stressed by various means to enrich for
      transcripts from genes expressed under such conditions. SNPs discovered in these
      sequences may be useful markers for mapping genes involved in interactions with
      the biotic and abiotic environment. The STS loci are distributed randomly over
      the genome. By comparison with the Col-0 genome sequence, we identified a total
      of 8051 SNPs and 637 insertion/deletion polymorphisms (InDel). Analysis of STS
      derived SNPs shows that most SNPs are rare, but that it is possible to identify
      intermediate frequency framework markers that can be used for genetic mapping in
      many different combinations of accessions. A substantial proportion of SNPs
      located in ORFs caused a change of the encoded amino acid. A comparison of the
      density of our SNP markers among accessions in both the EST and STS datasets,
      revealed that Cvi-0 is the most divergent accession from Col-0 among the 12
      accessions studied. All of these markers are freely available via the internet.

PMID- 12799365
TI  - Human leukocyte-derived arginine aminopeptidase. The third member of the
      oxytocinase subfamily of aminopeptidases.
AB  - In this study we report the cloning and characterization of a novel human
      aminopeptidase, which we designate leukocyte-derived arginine aminopeptidase (L
      RAP). The sequence encodes a 960-amino acid protein with significant homology to
      placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase.
      The predicted L-RAP contains the HEXXH(X)18E zinc-binding motif, which is
      characteristic of the M1 family of zinc metallopeptidases. Phylogenetic analysis
      indicates that L-RAP forms a distinct subfamily with placental leucine
      aminopeptidase and adipocyte-derived leucine aminopeptidase in the M1 family.
      Immunocytochemical analysis indicates that L-RAP is located in the lumenal side
      of the endoplasmic reticulum. Among various synthetic substrates tested, L-RAP
      revealed a preference for arginine, establishing that the enzyme is a novel
      arginine aminopeptidase with restricted substrate specificity. In addition to
      natural hormones such as angiotensin III and kallidin, L-RAP cleaved various N
      terminal extended precursors to major histocompatibility complex class I
      presented antigenic peptides. Like other proteins involved in antigen
      presentation, L-RAP is induced by interferon-gamma. These results indicate that L
      RAP is a novel aminopeptidase that can trim the N-terminal extended precursors to
      antigenic peptides in the endoplasmic reticulum.

PMID- 12799364
TI  - Mammalian mitochondrial initiation factor 2 supports yeast mitochondrial
      translation without formylated initiator tRNA.
AB  - Initiation of protein synthesis in mitochondria and chloroplasts is widely
      believed to require a formylated initiator methionyl-tRNA (fMet-tRNAfMet) in a
      process involving initiation factor 2 (IF2). However, yeast strains disrupted at
      the FMT1 locus, encoding mitochondrial methionyl-tRNA formyltransferase, lack
      detectable fMet-tRNAfMet but exhibit normal mitochondrial function as evidenced
      by normal growth on non-fermentable carbon sources. Here we show that
      mitochondrial translation products in Saccharomyces cerevisiae were synthesized
      in the absence of formylated initiator tRNA. ifm1 mutants, lacking the
      mitochondrial initiation factor 2 (mIF2), are unable to respire, indicative of
      defective mitochondrial protein synthesis, but their respiratory defect could be
      complemented by plasmid-borne copies of either the yeast IFM1 gene or a cDNA
      encoding bovine mIF2. Moreover, the bovine mIF2 sustained normal respiration in
      ifm1 fmt1 double mutants. Bovine mIF2 supported the same pattern of mitochondrial
      translation products as yeast mIF2, and the pattern did not change in cells
      lacking formylated Met-tRNAfMet. Mutant yeast lacking any mIF2 retained the
      ability to synthesize low levels of a subset of mitochondrially encoded proteins.
      The ifm1 null mutant was used to analyze the domain structure of yeast mIF2.
      Contrary to a previous report, the C terminus of yeast mIF2 is required for its
      function in vivo, whereas the N-terminal domain could be deleted. Our results
      indicate that formylation of initiator methionyl-tRNA is not required for
      mitochondrial protein synthesis. The ability of bovine mIF2 to support
      mitochondrial translation in the yeast fmt1 mutant suggests that this phenomenon
      may extend to mammalian mitochondria as well.

PMID- 12799366
TI  - Proteomics identification of acyl-acceptor and acyl-donor substrates for
      transglutaminase in a human intestinal epithelial cell line. Implications for
      celiac disease.
AB  - Transglutaminase (TG)-catalyzed cross-linking of both intracellular and
      extracellular proteins is an important biochemical event. However, increased
      concentrations of cross-linked proteins have been observed in many disorders.
      Moreover, TG-catalyzed modification of proteins might generate new self-antigens
      responsible for the autoimmune response, as in celiac disease. The identification
      of available substrates may offer an understanding of how the TG-catalyzed post
      translational modification has an impact on physiology and disease. We used a
      proteomic approach to identify TG-modified protein targets in human intestinal
      epithelial cells to determine the extent to which transglutaminase specifically
      contributes to celiac disease. Two probes were used for endogenous TG activity: 5
      (biotinamido)pentylamine, which represents the acyl-acceptor, and a biotinylated
      glutamine-containing peptide, which represents the acyl-donor. This approach
      identified >25 proteins, which range from 30,000 to 300,000 Daltons and can serve
      as acyl-acceptor and/or acyl-donor for transglutaminase. Some of them were known
      transglutaminase substrates, whereas others had not been previously identified.
      These targets include proteins involved in cytoskeletal network organization,
      folding of proteins, transport processes, and miscellaneous metabolic functions.

PMID- 12799367
TI  - Voltage dependence of the Ca2+-activated cation channel TRPM4.
AB  - TRPM4 is a Ca2+-activated but Ca2+-impermeable cation channel. An increase of
      [Ca2+]i induces activation and subsequent reduction of currents through TRPM4
      channels. This inactivation is strikingly decreased in cell-free patches. In
      whole cell and cell-free configuration, currents through TRPM4 deactivate rapidly
      at negative potentials. At positive potentials, currents are much larger and
      activate slowly. This voltage-dependent behavior induces a striking outward
      rectification of the steady state currents. The instantaneous current-voltage
      relationship, derived from the amplitude of tail currents following a prepulse to
      positive potentials, is linear. Currents show a Boltzmann type of activation; the
      fraction of open channels increases at positive potentials and is low at negative
      potentials. Voltage dependence is not due to block by divalent cations or to
      voltage-dependent binding of intracellular Ca2+ to an activator site, indicating
      that TRPM4 is a transient receptor potential channel with an intrinsic voltage
      sensing mechanism. Voltage dependence of TRPM4 may be functionally important,
      especially in excitable tissues generating plateau-like or bursting action
      potentials.

PMID- 12799368
TI  - Regulation of the yeast DPP1-encoded diacylglycerol pyrophosphate phosphatase by
      transcription factor Gis1p.
AB  - The Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate
      phosphatase catalyzes the dephosphorylation of diacylglycerol pyrophosphate to
      form phosphatidate and Pi. The enzyme also dephosphorylates phosphatidate to form
      diacylglycerol and Pi. Because diacylglycerol pyrophosphate, phosphatidate, and
      diacylglycerol have roles as lipid signal molecules in higher eukaryotic cells,
      it is important to understand how diacylglycerol pyrophosphate phosphatase is
      regulated. Analysis of DPP1 expression using PDPP1-lacZ reporter genes with a
      series of deletions from the 5' end of the promoter indicated sequences
      responsible for enzyme expression. Three binding sites (URSPDS) for transcription
      factor Gis1p were identified in the DPP1 promoter (consensus sequence of 5'
      T(A/T)AGGGAT-3'). A gis1 Delta mutant exhibited elevated levels of DPP1
      expression and diacylglycerol pyrophosphate phosphatase activity. Direct
      interaction between Gis1p and DPP1 promoter elements was demonstrated by
      electrophoretic mobility shift assays. Mutations in the three URSPDS elements
      within the DPP1 promoter abolished Gis1p-DNA interactions in vitro and abolished
      the regulation of DPP1 in vivo. These data indicated that Gis1p was a repressor
      of DPP1 expression. Phospholipid composition analysis of the gis1 Delta mutant
      showed that Gis1p played a role in regulating the cellular level of
      diacylglycerol pyrophosphate, as well as the levels of the major phospholipids
      phosphatidylethanolamine and phosphatidylcholine.

PMID- 12799369
TI  - Catecholamine secretory vesicle stimulus-transcription coupling in vivo.
      Demonstration by a novel transgenic promoter/photoprotein reporter and inhibition
      of secretion and transcription by the chromogranin A fragment catestatin.
AB  - Stimulation of chromaffin cell secretion in vitro triggers not only secretion but
      also resynthesis of just released catecholamines and chromogranin A, the
      precursor of the catecholamine release-inhibitory, nicotinic cholinergic
      antagonist peptide catestatin. Does stimulus-transcription coupling occur in
      vivo? And does catestatin antagonize secretion and transcription in vivo? To
      answer these questions, we employed a novel mouse strain harboring a chromogranin
      A promoter/firefly luciferase reporter transgene. Tissue-specific expression of
      the reporter was established by both luminescence and reverse transcription-PCR.
      Secretion and transcription in vivo were triggered by either direct nicotinic
      stimulation or vesicular transmitter depletion. Nicotinic blockade in vivo was
      attempted with either the classical antagonist chlorisondamine or the novel
      antagonist catestatin. Luciferase reporter expression was exquisitely sensitive
      over a large dynamic range, was specific for the transgenic animals, and
      paralleled typical neuroendocrine distribution of endogenous chromogranin A.
      Adrenal ontogeny revealed a rise of embryonic transgene expression until
      embryonal day 18, with an abrupt postnatal decline. Direct nicotinic stimulation
      of chromaffin cells caused catecholamine release and transgene transcription,
      each of which was nearly completely blocked by chlorisondamine. Similar adrenal
      results were obtained during vesicular catecholamine depletion. Both secretion
      and transcription were substantially blocked in the adrenal gland by catestatin.
      In brain and sympathetic nerve, stimulation of transcription was more modest, and
      reserpine responses were only incompletely blocked by chlorisondamine or
      catestatin, perhaps because of limited blood-brain barrier penetration by these
      cationic antagonists. Thus, nicotinic cholinergic stimulus-transcription coupling
      occurs in vivo and can be provoked either directly or indirectly (by vesicular
      transmitter depletion). Such coupling triggers the biosynthesis of chromogranin
      A, the precursor of catestatin. Catestatin itself blocks stimulation of both
      secretion and transcription in vivo. Thus, chromogranin A and its catestatin
      fragment may lie at the nexus of nicotinic cholinergic signaling in vivo.

PMID- 12799370
TI  - Vacuolar processing enzymes are essential for proper processing of seed storage
      proteins in Arabidopsis thaliana.
AB  - The proprotein precursors of storage proteins are post-translationally processed
      to produce their respective mature forms within the protein storage vacuoles of
      maturing seeds. To investigate the processing mechanism in vivo, we isolated
      Arabidopsis mutants that accumulate detectable amounts of the precursors of the
      storage proteins, 12 S globulins and 2 S albumins, in their seeds. All six
      mutants isolated have a defect in the beta VPE gene. VPE (vacuolar processing
      enzyme) is a cysteine proteinase with substrate specificity toward an asparagine
      residue. We further generated various mutants lacking different VPE isoforms:
      alpha VPE, beta VPE, and/or gamma VPE. More than 90% of VPE activity is abolished
      in the beta vpe-3 seeds, and no VPE activity is detected in the alpha vpe-1/beta
      vpe-3/gamma vpe-1 seeds. The triple mutant seeds accumulate no properly processed
      mature storage proteins. Instead, large amounts of storage protein precursors are
      found in the seeds of this mutant. In contrast to beta vpe-3 seeds, which
      accumulate both precursors and mature storage proteins, the other single (alpha
      vpe-1 and gamma vpe-1) and double (alpha vpe-1/gamma vpe-1) mutants accumulate no
      precursors in their seeds at all. Therefore, the vegetative VPEs, alpha VPE and
      gamma VPE, are not necessary for precursor processing in the presence of beta
      VPE, but partly compensates for the deficiency in beta VPE in beta vpe-3 seeds.
      In the absence of functional VPEs, a proportion of pro2S albumin molecules are
      alternatively cleaved by aspartic proteinase. This cleavage by aspartic
      proteinase is promoted by the initial processing of pro2S albumins by VPE. Our
      overall results suggest that seed-type beta VPE is most essential for the
      processing of storage proteins, and that the vegetative-type VPEs and aspartic
      proteinase complement beta VPE activity in this processing.

PMID- 12799372
TI  - Caspase-dependent alterations of Ca2+ signaling in the induction of apoptosis by
      hepatitis B virus X protein.
AB  - The hepatitis B virus X protein (HBx) is a multifunctional protein, acting on
      different targets (e.g. transcription factors, cytoplasmic kinases, and
      mitochondrial proteins) and exerting cellular effects as diverse as stimulation
      of cell proliferation and apoptosis. In its biological effects, the modulation of
      cellular Ca2+ signals has been proposed to be involved, but the direct assessment
      of Ca2+ homeostasis in HBx-transfected cells has not been carried out yet. In
      this work, we have employed for this purpose aequorin-based recombinant probes
      specifically targeted to intracellular organelles and microdomains. Using these
      probes, we observed that overexpression of HBx enhanced agonist-evoked cytosolic
      Ca2+ signals in HepG2 and HeLa cells, without affecting either the steady state
      of endoplasmic reticulum Ca2+ concentration or the kinetics of Ca2+ release.
      Rather, caspase-3-dependent cleavage of the plasma membrane Ca2+ ATPase could be
      demonstrated, and larger rises were detected in the cytoplasmic rim beneath the
      plasma membrane. In mitochondria, major morphological (fragmentation and
      swelling) and functional (reduced Ca2+ uptake) alterations were detected in HBx
      expressing cells. As to the cellular consequences, we observed that HBx-induced
      apoptosis was markedly reduced when the alterations in Ca2+ signaling (e.g. by
      loading a Ca2+ chelator or preventing PMCA cleavage) or the downstream effects
      (e.g. by inhibiting mitochondrial permeability transition) were prevented.
      Overall, these results indicate that HBx perturbs intracellular Ca2+ homeostasis,
      acting on the extrusion mechanisms, and that this effect plays an important role
      in the control of HBx-related apoptosis.

PMID- 12799371
TI  - ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic
      receptor.
AB  - G protein-coupled receptors can potentially activate phospholipase D (PLD) by a
      number of routes. We show here that the native M3 muscarinic receptor in 1321N1
      cells and an epitope-tagged M3 receptor expressed in COS7 cells substantially
      utilize an ADP-ribosylation factor (ARF)-dependent route of PLD activation. This
      pathway is activated at the plasma membrane but appears to be largely independent
      of G, phospholipase C, Ca2+ q/11, protein kinase C, tyrosine kinases, and
      phosphatidyl inositol 3-kinase. We report instead that it involves physical
      association of ARF with the M3 receptor as demonstrated by co-immunoprecipitation
      and by in vitro interaction with a glutathione S-transferase fusion protein of
      the receptor's third intracellular loop domain. Experiments with mutant
      constructs of ARF1/6 and PLD1/2 indicate that the M3 receptor displays a major
      ARF1-dependent route of PLD1 activation with an additional ARF6-dependent pathway
      to PLD1 or PLD2. Examples of other G protein-coupled receptors assessed in
      comparison display alternative pathways of protein kinase C- or ARF6-dependent
      activation of PLD2.

PMID- 12799373
TI  - Altered gene expression in liver from a murine model of hyperhomocysteinemia.
AB  - Cystathionine beta-synthase (CBS) deficiency causes severe hyperhomocysteinemia
      and other signs of homocystinuria syndrome, in particular a premature
      atherosclerosis with multiple thrombosis. However, the molecular mechanisms by
      which homocysteine could interfere with normal cell function are poorly
      understood in a whole organ like the liver, which is central to the catabolism of
      homocysteine. We used a combination of differential display and cDNA arrays to
      analyze differential gene expression in association with elevated hepatic
      homocysteine levels in CBS-deficient mice, a murine model of
      hyperhomocysteinemia. Expression of several genes was found to be reproducibly
      abnormal in the livers of heterozygous and homozygous CBS-deficient mice. We
      report altered expression of genes encoding ribosomal protein S3a and
      methylthioadenosine phosphorylase, suggesting such cellular growth and
      proliferation perturbations may occur in homozygous CBS-deficient mice liver.
      Many up- or down-regulated genes encoded cytochromes P450, evidence of
      perturbations of the redox potential in heterozygous and homozygous CBS-deficient
      mice liver. The expression of various genes involved in severe oxidative
      processes was also abnormal in homozygous CBS-deficient mice liver. Among them,
      the expression of heme oxygenase 1 gene was increased, concomitant with
      overexpression of heme oxygenase 1 at the protein level. Commensurate with the
      difference in hepatic mRNA paraoxonase 1 abundance, the mean hepatic activity of
      paraoxonase 1, an enzyme that protects low density lipoprotein from oxidation,
      was 3-fold lower in homozygous CBS-deficient mice. Heterozygous CBS-deficient
      mice, when fed a hyperhomocysteinemic diet, have also reduced PON1 activity,
      which demonstrates the effect of hyperhomocysteinemia in the paraoxonase 1
      activity.

PMID- 12799374
TI  - Identification of a novel binding site for platelet integrins alpha IIb beta 3
      (GPIIbIIIa) and alpha 5 beta 1 in the gamma C-domain of fibrinogen.
AB  - The interactions of platelets with fibrinogen mediate a variety of responses
      including adhesion, platelet aggregation, and fibrin clot retraction. Whereas it
      was assumed that interactions of the platelet integrin alpha IIb beta 3 with the
      AGDV sequence in the gamma C-domain of fibrinogen and/or RGD sites in the A alpha
      chains are involved in clot retraction and adhesion, recent data demonstrated
      that fibrinogen lacking these sites still supported clot retraction. These
      findings suggested that an unknown site in fibrinogen and/or other integrins
      participate in clot retraction. Here we have identified a sequence within gamma C
      that mediates binding of fibrinogen to platelets. Synthetic peptide duplicating
      the 365-383 sequence in gamma C, designated P3, efficiently inhibited clot
      retraction in a dose-dependent manner. Furthermore, P3 supported platelet
      adhesion and was an effective inhibitor of platelet adhesion to fibrinogen
      fragments. Analysis of overlapping peptides spanning P3 and mutant recombinant
      gamma C-domains demonstrated that the P3 activity is contained primarily within
      gamma 370-383. Integrins alpha IIb beta 3 and alpha 5 beta 1 were implicated in
      recognition of P3, since platelet adhesion to the peptide was blocked by function
      blocking monoclonal antibodies against these receptors. Direct evidence that
      alpha IIb beta 3 and alpha 5 beta 1 bind P3 was obtained by selective capture of
      these integrins from platelet lysates using a P3 affinity matrix. Thus, these
      data suggest that the P3 sequence in the gamma C-domain of fibrinogen defines a
      previously unknown recognition specificity of alpha IIb beta 3 and alpha 5 beta 1
      and may function as a binding site for these integrins.

PMID- 12799375
TI  - Mutations in the substrate binding site of thrombin-activatable fibrinolysis
      inhibitor (TAFI) alter its substrate specificity.
AB  - Thrombin-activable fibrinolysis inhibitor (TAFI) is a zymogen that inhibits the
      amplification of plasmin production when converted to its active form (TAFIa).
      TAFI is structurally very similar to pancreatic procarboxypeptidase B. TAFI also
      shares high homology in zinc binding and catalytic sites with the second basic
      carboxypeptidase present in plasma, carboxypeptidase N. We investigated the
      effects of altering residues involved in substrate specificity to understand how
      they contribute to the enzymatic differences between TAFI and carboxypeptidase N.
      We expressed wild type TAFI and binding site mutants in 293 cells. Recombinant
      proteins were purified and characterized for their activation and enzymatic
      activity as well as functional activity. Although the thrombin/thrombomodulin
      complex activated all the mutants, carboxypeptidase B activity of the activated
      mutants against hippuryl-arginine was reduced. Potato carboxypeptidase inhibitor
      inhibited the residual activity of the mutants. The functional activity of the
      mutants in a plasma clot lysis assay correlated with their chromogenic activity.
      The effect of the mutations on other substrates depended on the particular
      mutation, with some of the mutants possessing more activity against hippuryl-His
      leucine than wild type TAFIa. Thus mutations in residues around the substrate
      binding site of TAFI resulted in altered C-terminal substrate specificity.

PMID- 12799376
TI  - Purification and characterization of the MQH2:NO oxidoreductase from the
      hyperthermophilic archaeon Pyrobaculum aerophilum.
AB  - The membrane-bound NO reductase from the hyperthermophilic denitrifying archaeon
      Pyrobaculum aerophilum was purified to homogeneity. The enzyme displays MQH2:NO
      oxidoreductase (qNOR) activity, consists of a single subunit, and contains heme
      and nonheme iron in a 2:1 ratio. The combined results of EPR, resonance Raman,
      and UV-visible spectroscopy show that one of the hemes is bis-His-coordinated low
      spin (gz = 3.015; gy = 2.226; gx = 1.45), whereas the other heme adopts a high
      spin configuration. The enzyme also contains one nonheme iron center, which in
      the oxidized enzyme is antiferromagnetically coupled to the high spin heme. This
      binuclear high spin heme/nonheme iron center is EPR-silent and the site of NO
      reduction. The reduced high spin heme is bound to a neutral histidine and can
      bind CO to form of a low spin complex. The oxidized high spin heme binds NO,
      yielding a ferric nitrosyl complex, the intermediate causing the commonly found
      substrate inhibition in NO reductases (Ki(NO) = 7 microm). The qNOR as present in
      the membrane is, in contrast to the purified enzyme, quite thermostable,
      incubation at 100 degrees C for 86 min leading to 50% inhibition. The pure enzyme
      lacks heme b and instead contains stoichiometric amounts of hemes Op1 and Op2,
      ethenylgeranylgeranyl and hydroxyethylgeranylgeranyl derivatives of heme b,
      respectively. The archaeal qNOR is the first example of a NO reductase, which
      contains modified hemes reminiscent of cytochrome bo3 and aa3 oxidases. This
      report is the first describing the purification and structural and spectroscopic
      properties of a thermostable NO reductase.

PMID- 12799377
TI  - Purification, characterization, and identification of a sphingomyelin synthase
      from Pseudomonas aeruginosa. PlcH is a multifunctional enzyme.
AB  - Sphingomyelin synthase is the enzyme that synthesizes sphingomyelin (SM) in
      mammalian cells by transferring a phosphorylcholine moiety from
      phosphatidylcholine to ceramide. Despite its importance, the gene and/or the
      protein responsible for this activity has not yet been identified. Here we report
      the purification, identification, and biochemical characterization of an
      enzymatic activity that synthesizes SM in Pseudomonas aeruginosa. SM synthase
      like activity was found secreted in the culture medium of P. aeruginosa, strains
      PA01 and PAK, whereas it could not be detected in cultures of Escherichia coli.
      From the medium of PAK cultures, SM synthase was purified through sequential
      chromatographic columns. After separation on polyacrylamide-SDS gels and
      visualization by silver staining, the purified enzyme showed two bands, one of
      approximately 75 kDa and one of 30-35 kDa. Interestingly, the highly purified SM
      synthase preparation also showed neutral sphingomyelinase activity. We therefore
      investigated whether the protein we purified as SM synthase could actually be the
      previously identified PlcH, a 78-kDa phospholipase C known to hydrolyze
      phosphatidylcholine and SM in P. aeruginosa. First, the purified SM synthase
      preparation contained a 78-kDa protein that reacted with monoclonal antibodies
      raised against purified PlcH. Second, purified PlcH showed SM synthase activity.
      Third, using different knockout mutant strains for the PlcH operon, PlcH was
      found to be necessary for SM synthase activity in P. aeruginosa. Interestingly,
      SM synthase activity was specific to the Pseudomonas PlcH as other bacterial
      phospholipases did not display SM synthase activity. Biochemical studies on the
      Pseudomonas SM synthase confirmed that it is a transferase, similar to the
      mammalian enzyme, that specifically recognizes the choline head-group and the
      primary hydroxyl on ceramide. This SM synthase did not have reverse transferase
      activity. In conclusion, the Pseudomonas PlcH also exerts SM synthase activity;
      therefore, for the first time, we have identified a structural gene for a SM
      synthase.

PMID- 12799378
TI  - A direct beta-catenin-independent interaction between androgen receptor and T
      cell factor 4.
AB  - T cell factor (Tcf) proteins bind beta-catenin and are downstream effectors of
      Wnt/beta-catenin signals. A recently demonstrated interaction between beta
      catenin and the androgen receptor (AR) ligand binding domain has suggested that
      AR may be a Tcf-independent Wnt/beta-catenin effector. This study demonstrates
      that there is a direct interaction between the AR DNA binding domain (DBD) and
      Tcf4. Tcf4 bound specifically to a glutathione S-transferase-ARDBD fusion protein
      and could be coimmunoprecipitated with beta-catenin and transfected AR or
      endogenous AR in prostate cancer cells. Transfected Tcf4 repressed the
      transcriptional activity of full-length AR and a VP16-ARDBD fusion protein, and
      this repression was only partially reversed by transfected beta-catenin. AR
      activation by cyproterone acetate, a partial agonist that did not support beta
      catenin binding to the AR, was also repressed by Tcf4, further indicating that
      repression was not due to beta-catenin sequestration. Tcf4 could recruit beta
      catenin to the AR DBD in vitro and to the cyproterone acetate-liganded AR in
      vivo. Chromatin immunoprecipitation experiments in LNCaP prostate cancer cells
      showed that endogenous AR was bound to a Tcf4-responsive element in the c-myc
      promoter. These findings indicate that AR and Tcf4 can interact directly and that
      this interaction may occur on the promoters or enhancers of particular genes. The
      direct AR-Tcf4 interaction, in conjunction AR- and Tcf4-beta-catenin binding,
      provides a mechanism for cooperative and selective gene regulation by AR and the
      Wnt/beta-catenin-Tcf pathway that may contribute to normal and neoplastic
      prostate growth.

PMID- 12799379
TI  - Molecular and biochemical characterization of an enzyme responsible for the
      formation of hypericin in St. John's wort (Hypericum perforatum L.).
AB  - A major gene termed Hyp-1 encoding for hypericin (HyH) biosynthesis was cloned
      and characterized from Hypericum perforatum (St. John's wort) cell cultures. H.
      perforatum leaves are widely used as an herbal remedy in the treatment of mild to
      moderate depression. Hypericin, a photosensitive and red-colored
      naphthodianthrone, has been reported as the bioactive compound responsible for
      reversing the depression symptoms. In this study a novel red-color-based colony
      screening method for examining a cDNA library (lambda-TriplEX2) derived from H.
      perforatum cell cultures revealed the gene responsible for hypericin biosynthesis
      after the administration of emodin, a precursor of hypericin. The selected clones
      were expressed in Escherichia coli (BM 25.8 line) and were further screened for
      biosynthesis of emodin to hypericin, which resulted in an 84.6% conversion. The
      full-length cDNA sequence of Hyp-1 is 782 nucleotides in length with an open
      reading frame of 477 nucleotides coding for a protein of 159 amino acids, with a
      45.1% homology to Bet.v.1 class allergens. Reverse transcriptase-PCR analysis
      showed high levels of Hyp-1 transcripts in dark-grown cell cultures compared with
      the levels in light-grown cell cultures and leaves. Southern blot analysis showed
      the presence of a single Hyp-1 gene in H. perforatum. Furthermore, Hyp-1 was
      expressed with a His6 affinity tag linked to its N terminal region using the
      expression vector pET-28a, and the recombinant Hyp-1 protein was able to convert
      HyH from emodin under in vitro conditions. HyH product inhibition was observed
      with emodin analogues, rhein, rhein methyl ester, and DNA3-55-1. Our results
      demonstrate a direct and complex conversion of emodin to HyH that is solely
      catalyzed by Hyp-1, a Bet.v.1 class allergen from H. perforatum.

PMID- 12799381
TI  - Sufficiency of the reactive site loop of maspin for induction of cell-matrix
      adhesion and inhibition of cell invasion. Conversion of ovalbumin to a maspin
      like molecule.
AB  - Maspin, an ov-serpin, inhibits tumor invasion and induces cell adhesion to
      extracellular matrix molecules. Here, we use maspin/ovalbumin chimeric proteins
      and the maspin reactive site loop (RSL) peptide to characterize the role of the
      RSL in maspin-mediated functions. Replacement of the RSL plus the C-terminal
      region or the RSL alone of maspin with that of ovalbumin resulted in the loss of
      the stimulatory effect on adhesion of corneal stromal cells to type I collagen,
      fibronectin, and laminin and of mammary carcinoma MDA-MB-231 cells to
      fibronectin. Maspin with ovalbumin as the C-terminal region retained activity,
      suggesting the maspin C-terminal polypeptide is not required. An R340Q mutant
      retained full maspin activity; however, an R340A mutant lost activity. This
      indicates the arginine side chain at the putative P1 site forms a hydrogen bond
      and not an ionic bond. The RSL peptide (P10-P5', amino acids 330-345) alone
      induced cell-matrix adhesion of mammary carcinoma cells and corneal stromal cells
      and inhibited invasion of the carcinoma cells. Substitution of the RSL of
      ovalbumin with that of maspin converted inactive ovalbumin into a fully active
      molecule. Maspin bound specifically to the surface of the mammary carcinoma cells
      with a kd of 367 +/- 67 nM and 32.0 +/- 2.2 x 10(6) binding sites/cell. The
      maspin RSL peptide inhibited binding, suggesting the RSL is involved in maspin
      binding to cells. Sufficiency of the maspin RSL for activity suggests the
      mechanism by which maspin regulates cell-matrix adhesion and tumor cell invasion
      does not involve the serpin mechanism of protease inhibition.

PMID- 12799380
TI  - Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T
      lymphocytes through the transcription factor Ikaros. Evidence for a synergistic
      effect of leptin.
AB  - Physiological concentrations of progesterone stimulate the activity of the
      endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human T
      lymphocytes, up to a approximately 270% over the untreated controls. Stimulation
      of FAAH occurred through up-regulation of gene expression at transcriptional and
      translational level and was specific. Indeed, neither the activity of the
      anandamide-synthesizing N-acyltransferase and phospholipase D, nor the activity
      of the anandamide transporter, nor the binding to cannabinoid receptors were
      affected by progesterone under the same experimental conditions. The activation
      of FAAH by progesterone was paralleled by a decrease (down to 60%) of the
      cellular levels of anandamide and involved increased nuclear levels of the
      transcription factor Ikaros. Analysis of the FAAH promoter showed an Ikaros
      binding site, and mutation of this site prevented FAAH activation by progesterone
      in transient expression assays. Electrophoretic mobility shift and supershift
      assays further corroborated the promoter activity data. Furthermore, the effect
      of progesterone on FAAH promoter was additive to that of physiological amounts of
      leptin, which binds to a cAMP response element-like site in the promoter region.
      Taken together, these results suggest that progesterone and leptin, by up
      regulating the FAAH promoter at different sites, enhance FAAH expression, thus
      tuning the immunomodulatory effects of anandamide. These findings might also have
      critical implications for human fertility.

PMID- 12799382
TI  - A novel membrane-associated glycovariant of BEHAB/brevican is up-regulated during
      rat brain development and in a rat model of invasive glioma.
AB  - BEHAB (brain-enriched hyaluronan-binding protein)/brevican is the most abundant
      chondroitin sulfate proteoglycan in the extracellular matrix of the adult rat
      brain. BEHAB/brevican expression is up-regulated coincident with glial cell
      proliferation and/or motility, including during early central nervous system
      development and in invasive glioma. An understanding of the molecular
      interactions that mediate BEHAB/brevican function is still in its infancy because
      of the existence of several BEHAB/brevican isoforms, each of which may mediate
      different functions. Here, we describe a novel BEHAB/brevican isoform, B/b130,
      and demonstrate that it is neither the glycosylphosphatidylinositol-linked splice
      variant of BEHAB/brevican nor a cleavage product of the full-length protein
      (B/b150). B/b130 is an underglycosylated isoform of BEHAB/brevican, lacking
      glycosaminoglycan chains as well as most of the sugars that invest B/b150. B/b130
      localizes exclusively to the particulate fraction of rat brain and associates
      with the cell membrane by a previously undescribed calcium-independent mechanism.
      In addition, B/b130 is the major isoform of BEHAB/brevican that is up-regulated
      in a rat model of invasive glioma and may therefore contribute to the invasive
      ability of glioma cells. Further understanding of BEHAB/brevican isoforms will
      advance our knowledge of the function of this ECM component and may help identify
      new potential therapeutic targets for primary brain tumors.

PMID- 12799383
TI  - Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin
      through tyrosine phosphorylation of G alpha q.
AB  - The intracellularly acting Pasteurella multocida toxin (PMT) is a potent mitogen
      that stimulates Gq-dependent formation of inositol trisphosphate. We show that
      PMT, a nontoxic mutant of PMT (PMTC1165S), and bombesin each stimulate time
      dependent phosphorylation of G alpha q at tyrosine 349. Although PMT and
      PMTC1165S each cause phosphorylation of G alpha q, only the wild-type toxin
      activates Gq. Pretreatment of cells with wild-type or mutant PMT potentiated the
      formation of inositol phosphates stimulated by bombesin equally. These data show
      that PMT potentiates bombesin receptor signaling through tyrosine phosphorylation
      of Gq and distinguishes between the two proposed models of Gq activation, showing
      that tyrosine phosphorylation is not linked to receptor uncoupling.

PMID- 12799384
TI  - Molecular heterogeneity of the SHAP-hyaluronan complex. Isolation and
      characterization of the complex in synovial fluid from patients with rheumatoid
      arthritis.
AB  - We previously found that a covalent complex of SHAPs (serum-derived hyaluronan
      associated proteins), the heavy chains of inter-alpha-trypsin inhibitor family
      molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with
      rheumatoid arthritis, and the complex is circulated in patient plasma at high
      concentrations. How the SHAP-HA complex participates in this disease is unknown.
      To address this question, it is essential to clarify the structural features of
      this macromolecule. The SHAP-HA complex purified from synovial fluid of the
      patients by three sequential CsCl isopycnic centrifugations was heterogeneous in
      density, and the fractions with different densities had distinct SHAP-to-HA
      ratios. Agarose gel electrophoresis and column chromatography revealed that there
      was no apparent difference in the size distribution of HA to which SHAPs were
      bound between the fractions with different densities. The SHAP-HA complex in the
      higher density fraction had fewer SHAP molecules per HA chain. Therefore, the
      difference between the fractions with different densities was due to a
      heterogeneous population of the SHAP-HA complex, namely the different number of
      SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the
      purified preparations, we estimated that an HA chain with a molecular weight of 2
      x 106 has as many as five covalently bound SHAPs, which could give a
      proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA
      complex tends to form aggregates, judging from the migration and elution profiles
      in agarose gel electrophoresis and gel filtration, respectively. The multivalent
      feature of the SHAP-HA complex was also confirmed by the negative staining
      electron micrographic images of the purified fractions. Taken together, those
      structural characteristics may underlie the aggregate-forming and extracellular
      matrix-stabilizing ability of the SHAP-HA complex.

PMID- 12799385
TI  - A critical role for ATP in the stimulation of retinal guanylyl cyclase by
      guanylyl cyclase-activating proteins.
AB  - It has been believed that retinal guanylyl cyclase (retGC), a key enzyme in the
      cGMP recovery to the dark state, is solely activated by guanylyl cyclase
      activating proteins (GCAPs) in a Ca2+-sensitive manner. However, a question has
      arisen as to whether the observed GCAP stimulation of retGC is sufficient to
      account for the cGMP recovery because the stimulated activity measured in vitro
      is less than the light/GTP-activated cGMP phosphodiesterase activity. Here we
      report that the retGC activation by GCAPs is larger than previously reported and
      that a preincubation with adenine nucleotide is essential for the large
      activation. Under certain conditions, ATP is two times more effective than
      adenylyl imidodiphosphate (AMP-PNP), a hydrolysis-resistant ATP analog; however,
      this study mainly used AMP-PNP to focus on the role of adenine nucleotide binding
      to retGC. When photoreceptor outer segment homogenates are preincubated with AMP
      PNP (EC50 = 0.65 +/- 0.20 mM), GCAP2 enhanced the retGC activity 10-13 times over
      the control rate. Without AMP-PNP, GCAP2 stimulated the control activity only 3-4
      fold as in previous reports. The large activation is due to a GCAP2-dependent
      increase in Vmax without an alteration of retGC affinity for GCAP2 (EC50 = 47.9
      +/- 2.7 nM). GCAP1 stimulated retGC activity in a similar fashion but with lower
      affinity (EC50 = 308 nM). In the AMP-PNP preincubation, low Ca2+ concentrations
      are not required, and retGC exists as a monomeric form. This large activation is
      accomplished through enhanced action of GCAPs as shown by Ca2+ inhibition of the
      activity (IC50 = 178 nM). We propose that retGC is activated by a two-step
      mechanism: a conformational change by ATP binding to its kinase homology domain
      under high Ca2+ concentrations that allows large enhancement of GCAP activation
      under low Ca2+ concentrations.

PMID- 12799387
TI  - The contribution of polar group burial to protein stability is strongly context
      dependent.
AB  - We previously suggested that proteins gain more stability from the burial and
      hydrogen bonding of polar groups than from the burial of nonpolar groups (Pace,
      C. N. (2001) Biochemistry 40, 310-313). To study this further, we prepared eight
      Thr-to-Val mutants of RNase Sa, four in which the Thr side chain is hydrogen
      bonded and four in which it is not. We measured the stability of these mutants by
      analyzing their thermal denaturation curves. The four hydrogen-bonded Thr side
      chains contribute 1.3 +/- 0.9 kcal/mol to the stability; those that are not still
      contribute 0.4 +/- 0.9 kcal/mol to the stability. For 40 Thr-to-Val mutants of 11
      proteins, the average decrease in stability is 1.0 +/- 1.0 kcal/mol when the Thr
      side chain is hydrogen-bonded and 0.0 +/- 0.5 kcal/mol when it is not. This is
      clear evidence that hydrogen bonds contribute favorably to protein stability. In
      addition, we prepared four Val-to-Thr mutants of RNase Sa, measured their
      stability, and determined their crystal structures. In all cases, the mutants are
      less stable than the wild-type protein, with the decreases in stability ranging
      from 0.5 to 4.4 kcal/mol. For 41 Val-to-Thr mutants of 11 proteins, the average
      decrease in stability is 1.8 +/- 1.3 kcal/mol and is unfavorable for 40 of 41
      mutants. This shows that placing an [bond]OH group at a site designed for a
      [bond]CH3 group is very unfavorable. So, [bond]OH groups can contribute favorably
      to protein stability, even if they are not hydrogen-bonded, if the site was
      selected for an [bond]OH group, but they will make an unfavorable contribution to
      stability, even if they are hydrogen-bonded, when they are placed at a site
      selected for a [bond]CH3 group. The contribution that polar groups make to
      protein stability depends strongly on their environment.

PMID- 12799386
TI  - Structural characterization of native mouse zona pellucida proteins using mass
      spectrometry.
AB  - The zona pellucida is an extracellular matrix consisting of three glycoproteins
      that surrounds mammalian eggs and mediates fertilization. The primary structures
      of mouse ZP1, ZP2, and ZP3 have been deduced from cDNA. Each has a predicted
      signal peptide and a transmembrane domain from which an ectodomain must be
      released. All three zona proteins undergo extensive co- and post-translational
      modifications important for secretion and assembly of the zona matrix. In this
      report, native zonae pellucidae were isolated and structural features of
      individual zona proteins within the mixture were determined by high resolution
      electrospray mass spectrometry. Complete coverage of the primary structure of
      native ZP3, 96% of ZP2, and 56% of ZP1, the least abundant zona protein, was
      obtained. Partial disulfide bond assignments were made for each zona protein, and
      the size of the processed, native protein was determined. The N termini of ZP1
      and ZP3, but not ZP2, were blocked by cyclization of glutamine to pyroglutamate.
      The C termini of ZP1, ZP2, and ZP3 lie upstream of a dibasic motif, which is part
      of, but distinct from, a proprotein convertase cleavage site. The zona proteins
      are highly glycosylated and 4/4 potential N-linkage sites on ZP1, 6/6 on ZP2, and
      5/6 on ZP3 are occupied. Potential O-linked carbohydrate sites are more
      ubiquitous, but less utilized.

PMID- 12799388
TI  - Physical activity promotion through primary care.

PMID- 12799390
TI  - Bioterror exercise tests agencies' mettle.

PMID- 12799389
TI  - Cystic fibrosis gene testing a challenge: experts say widespread use is creating
      unnecessary risks.

PMID- 12799395
TI  - From the Centers for Disease Control and Prevention. Severe acute respiratory
      syndrome--Taiwan, 2003.

PMID- 12799396
TI  - From the Centers for Disease Control and Prevention. Elevated mortality
      associated with armed conflict--Democratic Republic of Congo, 2002.

PMID- 12799397
TI  - From the Centers for Disease Control and Prevention. Update: Severe acute
      respiratory syndrome--United States, May 21, 2003.

PMID- 12799398
TI  - Passive smoking and dental caries in children.

PMID- 12799399
TI  - Methods of estimating years of life lost due to obesity.

PMID- 12799400
TI  - Electrocardiographic diagnosis of pericarditis.

PMID- 12799401
TI  - Sperm changes in men exposed to polychlorinated biphenyls and dibenzofurans.

PMID- 12799402
TI  - Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a
      randomized trial.
AB  - CONTEXT: Blacks are disproportionately affected by stroke, and they are about 2
      times more likely than most other individuals in the United States to die of or
      experience stroke. OBJECTIVE: To determine the efficacy and safety of aspirin and
      ticlopidine to prevent recurrent stroke in black patients. DESIGN, SETTING, AND
      PATIENTS: Randomized, double-blind, investigator-initiated, multicenter trial of
      1809 black men and women who recently had a noncardioembolic ischemic stroke and
      who were recruited between December 1992 and October 2001 from 62 academic and
      community hospitals in the United States and followed up for up to 2 years.
      INTERVENTION: A total of 902 patients received 500 mg/d of ticlopidine and 907
      received 650 mg/d of aspirin. MAIN OUTCOME MEASURES: Recurrent stroke, myocardial
      infarction, or vascular death was the composite primary end point (according to
      intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.
      RESULTS: The blinded phase of the study was halted after about 6.5 years when
      futility analyses revealed a less than 1% probability of ticlopidine being shown
      superior to aspirin in the prevention of the primary outcome end point. The
      primary outcome of recurrent stroke, myocardial infarction, or vascular death was
      reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of
      907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval,
      0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not
      differ significantly (P =.12 by log-rank test). Kaplan-Meier curves for time to
      the secondary outcome of fatal or nonfatal stroke approached a statistically
      significant reduction favoring aspirin over ticlopidine (P =.08 by log-rank
      test). The frequency of laboratory-determined serious neutropenia was 3.4% for
      patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P =.12) and
      0.3% vs 0.2% for thrombocytopenia, respectively (P =.69). One ticlopidine-treated
      patient developed thrombocytopenia, which was thought to be a case of possible
      thrombotic thrombocytopenia purpura, and recovered after therapy with
      plasmapheresis. CONCLUSIONS: During a 2-year follow-up, we found no statistically
      significant difference between ticlopidine and aspirin in the prevention of
      recurrent stroke, myocardial infarction, or vascular death. However, there was a
      nonsignificant trend for reduction of fatal or nonfatal stroke among those in the
      aspirin group. Based on these data and the risk of serious adverse events with
      ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black
      patients with noncardioembolic ischemic stroke.

PMID- 12799403
TI  - Neonatal mortality in weekend vs weekday births.
AB  - CONTEXT: Increases in neonatal mortality for infants born on the weekend were
      last noted several decades ago. Although the current health care environment has
      raised concern about the adequacy of weekend care, there have been no
      contemporary evaluations of daily patterns of births, obstetric intervention, and
      case mix-adjusted neonatal mortality. OBJECTIVE: To compare the neonatal
      mortality of infants born on weekdays and weekends. DESIGN, SETTING, AND
      PARTICIPANTS: Case series of 1 615 041 live births (weight >or=500 g) in
      California between 1995-1997 to determine patterns of births, cesarean
      deliveries, and neonatal deaths. Analyses were stratified by birth weight and
      delivery method. To assess the role of weekend differences in case mix, observed
      and birth weight-adjusted odds ratios (ORs) for increased weekend mortality were
      estimated using logistic regression. MAIN OUTCOME MEASURE: Birth weight-adjusted
      neonatal mortality. RESULTS: There was a 17.5% decrease in births on weekends,
      accompanied by a decrease in the proportion of cesarean deliveries from 22% on
      weekdays to 16% on weekends. Weekend decreases in births were least pronounced in
      smaller infants, resulting in a weekend concentration of high-mortality, very low
      birth-weight (<1500 g) births. Observed neonatal mortality increased from 2.80
      per 1000 weekday births to 3.12 per 1000 weekend births (OR, 1.12; 95% confidence
      interval [CI], 1.05-1.19; P =.001) for all births, and from 4.94 to 6.85 (OR,
      1.39; 95% CI, 1.25-1.55; P<.001) for cesarean deliveries. After adjusting for
      birth weight, the increased odds of death for infants born on the weekend were no
      longer significant. CONCLUSIONS: The provision of optimal care regardless of the
      day of week is an important goal for perinatal medicine. Comparing the neonatal
      mortality of infants born on weekdays and weekends provides a straightforward
      assessment of this goal. After controlling for birth weight, we found no evidence
      that the quality of perinatal care in California was compromised during the
      weekend.

PMID- 12799404
TI  - Computer use and carpal tunnel syndrome: a 1-year follow-up study.
AB  - CONTEXT: Computer use is increasingly common among many working populations, and
      concern exists about possible adverse effects of computer use, such as carpal
      tunnel syndrome (CTS). OBJECTIVES: To estimate the prevalence and incidence of
      possible CTS and to evaluate the contribution of use of mouse devices and
      keyboards to the risk of possible CTS. DESIGN AND SETTING: A 1-year follow-up
      study with questionnaires conducted in 2000 and 2001 at 3500 workplaces in
      Denmark, followed on each of the 2 occasions by a clinical interview on symptom
      distribution and frequency. PARTICIPANTS: The questionnaire was sent to 9480
      members of a trade union, with an initial response rate of 73% (n = 6943), and
      82% (n = 5658) at follow-up. MAIN OUTCOME MEASURES: At baseline, there were 3
      outcome measures: tingling/numbness in the right hand once a week or more as
      reported in the questionnaire; tingling, numbness, and pain in the median nerve
      in the right hand confirmed by clinical interview; and tingling, numbness, and
      pain in the median nerve in the right hand at night confirmed by clinical
      interview. At 1 year of follow-up the main outcome of interest was onset of
      symptoms among participants who had no or minor symptoms at baseline. RESULTS:
      The overall self-reported prevalence of tingling/numbness in the right hand at
      baseline was 10.9%. The interview confirmed that prevalence of tingling/numbness
      in the median nerve was 4.8%, of which about one third, corresponding to a
      prevalence of 1.4%, experienced symptoms at night. Onset of new symptoms in the 1
      year follow-up was 5.5%. In the cross-sectional comparisons and in the follow-up
      analyses, there was an association between use of a mouse device for more than 20
      h/wk and risk of possible CTS but no statistically significant association with
      keyboard use. CONCLUSIONS: The occurrence of possible CTS in the right hand was
      low. The study emphasizes that computer use does not pose a severe occupational
      hazard for developing symptoms of CTS.

PMID- 12799405
TI  - Incremental treatment costs in national cancer institute-sponsored clinical
      trials.
AB  - CONTEXT: Concern about additional costs for direct patient care impedes efforts
      to enroll patients in clinical trials. But generalizable evidence substantiating
      these concerns is lacking. OBJECTIVE: To assess the additional cost of treating
      cancer patients in the National Cancer Institute (NCI)-sponsored clinical trials
      in the United States across a range of trial phases, treatment modalities, and
      patient care settings. DESIGN: Retrospective cost study using a multistage,
      stratified, random sample of patients enrolled in 1 of 35 active phase 3 trials
      or phase 1 or any phase 2 trials between October 1, 1998, and December 31, 1999.
      Unadjusted and adjusted costs were compared and related to trial phase,
      institution type, and vital status. SETTING AND PARTICIPANTS: A representative
      sample of 932 cancer patients enrolled in nonpediatric, NCI-sponsored clinical
      trials and 696 nonparticipants with a similar stage of disease not enrolled in a
      research protocol from 83 cancer clinical research institutions across the United
      States. MAIN OUTCOME MEASURES: Direct treatment costs as measured using a
      combination of medical records, telephone survey, and Medicare claims data.
      Administrative and other research costs were excluded. RESULTS: The incremental
      costs of direct care in trials were modest. Over approximately a 2.5-year period,
      adjusted costs were 6.5% higher for trial participants than nonparticipants
      (35,418 dollars vs 33,248 dollars; P =.11). Cost differences for phase 3 studies
      were 3.5% (P =.22), lower than for phase 1 or 2 trials (12.8%; P =.20). Trial
      participants who died had higher costs than nonparticipants who died (17.9%;
      39,420 dollars vs 33,432 dollars, respectively; P =.15). CONCLUSIONS: Treatment
      costs for nonpediatric clinical trial participants are on average 6.5% higher
      than what they would be if patients did not enroll. This implies total
      incremental treatment costs for NCI-sponsored trials of 16 million dollars in
      1999. Incremental costs were higher for patients who died and who were in early
      phase studies although these findings deserve further scrutiny. Overall, the
      additional treatment costs of an open reimbursement policy for government
      sponsored cancer clinical trials appear minimal.

PMID- 12799406
TI  - Impact of HIV infection and HAART on serum lipids in men.
AB  - CONTEXT: Alterations in serum lipid values have been widely reported among
      persons infected with human immunodeficiency virus (HIV) type 1 treated with
      highly active antiretroviral therapy (HAART), but no data have yet been reported
      on changes from preseroconversion lipid values. OBJECTIVE: To describe changes in
      serum cholesterol levels associated with HIV infection and antiretroviral
      medication exposure, and 1-time assessment of triglyceride levels post-HAART
      initiation. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter AIDS Cohort Study,
      a prospective study in which homosexual and bisexual men were enrolled and from
      which 50 of 517 HIV seroconverters were drawn for the analysis herein, who later
      initiated HAART, involving measurements of stored serum samples obtained between
      1984 and 2002. MAIN OUTCOME MEASURES: Changes in levels of total cholesterol
      (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein
      cholesterol (LDL-C) at 6 time points during an average of 12 years; 1-time
      assessment of triglyceride levels from the third post-HAART clinic visit.
      RESULTS: Among the 50 men, notable declines in mean serum TC (-30 mg/dL [-0.78
      mmol/L]), HDL-C (-12 mg/dL [-0.31 mmol/L]), and LDL-C values (-22 mg/dL [-0.57
      mmol/L]) were observed after HIV infection. Following HAART initiation, there
      were large increases in mean TC and LDL-C values (50 and 21 mg/dL [1.30 and 0.54
      mmol/L], respectively); however, the mean changes from the preseroconversion
      values were 20 mg/dL (0.52 mmol/L) (95% confidence interval [CI], -1 to 41) and 
      1 mg/dL (-0.03 mmol/L) (95% CI, -25 to 22), respectively. Mean HDL-C remained
      below baseline levels throughout follow-up. The median value (interquartile
      range) of triglycerides was 225 mg/dL (2.54 mmol/L) (147-331 mg/dL). CONCLUSIONS:
      Before treatment, HIV infection results in substantial decreases in serum TC, HDL
      C, and LDL-C levels. Subsequent HAART initiation is associated with increases in
      TC and LDL-C but little change in HDL-C. Increases in TC and LDL-C observed after
      about 3 years of HAART possibly represent a return to preinfection serum lipid
      levels after accounting for expected age-related changes.

PMID- 12799407
TI  - Monitoring sedation status over time in ICU patients: reliability and validity of
      the Richmond Agitation-Sedation Scale (RASS).
AB  - CONTEXT: Goal-directed delivery of sedative and analgesic medications is
      recommended as standard care in intensive care units (ICUs) because of the impact
      these medications have on ventilator weaning and ICU length of stay, but few of
      the available sedation scales have been appropriately tested for reliability and
      validity. OBJECTIVE: To test the reliability and validity of the Richmond
      Agitation-Sedation Scale (RASS). DESIGN: Prospective cohort study. SETTING: Adult
      medical and coronary ICUs of a university-based medical center. PARTICIPANTS:
      Thirty-eight medical ICU patients enrolled for reliability testing (46% receiving
      mechanical ventilation) from July 21, 1999, to September 7, 1999, and an
      independent cohort of 275 patients receiving mechanical ventilation were enrolled
      for validity testing from February 1, 2000, to May 3, 2001. MAIN OUTCOME
      MEASURES: Interrater reliability of the RASS, Glasgow Coma Scale (GCS), and
      Ramsay Scale (RS); validity of the RASS correlated with reference standard
      ratings, assessments of content of consciousness, GCS scores, doses of sedatives
      and analgesics, and bispectral electroencephalography. RESULTS: In 290-paired
      observations by nurses, results of both the RASS and RS demonstrated excellent
      interrater reliability (weighted kappa, 0.91 and 0.94, respectively), which were
      both superior to the GCS (weighted kappa, 0.64; P<.001 for both comparisons).
      Criterion validity was tested in 411-paired observations in the first 96 patients
      of the validation cohort, in whom the RASS showed significant differences between
      levels of consciousness (P<.001 for all) and correctly identified fluctuations
      within patients over time (P<.001). In addition, 5 methods were used to test the
      construct validity of the RASS, including correlation with an attention screening
      examination (r = 0.78, P<.001), GCS scores (r = 0.91, P<.001), quantity of
      different psychoactive medication dosages 8 hours prior to assessment (eg,
      lorazepam: r = - 0.31, P<.001), successful extubation (P =.07), and bispectral
      electroencephalography (r = 0.63, P<.001). Face validity was demonstrated via a
      survey of 26 critical care nurses, which the results showed that 92% agreed or
      strongly agreed with the RASS scoring scheme, and 81% agreed or strongly agreed
      that the instrument provided a consensus for goal-directed delivery of
      medications. CONCLUSIONS: The RASS demonstrated excellent interrater reliability
      and criterion, construct, and face validity. This is the first sedation scale to
      be validated for its ability to detect changes in sedation status over
      consecutive days of ICU care, against constructs of level of consciousness and
      delirium, and correlated with the administered dose of sedative and analgesic
      medications.

PMID- 12799408
TI  - Prolonged therapeutic hypothermia after traumatic brain injury in adults: a
      systematic review.
AB  - CONTEXT: The benefits of therapeutic hypothermia as a treatment for traumatic
      brain injury (TBI) remain unclear. OBJECTIVE: To explore the effects of depth,
      duration, and rate of rewarming after discontinuation of hypothermia on mortality
      and neurologic outcome in adults after TBI. DATA SOURCES: An electronic search of
      MEDLINE (OVID), EMBASE, Current Contents, the Cochrane library and a hand search
      of key journals were performed. Corresponding authors of identified studies were
      contacted for additional unpublished or ongoing clinical trials. STUDY SELECTION:
      All randomized controlled trials of therapeutic hypothermia for at least 24 hours
      vs normothermia in adults with TBI. DATA EXTRACTION: Demographic and clinical
      data, hypothermia interventions and cointerventions, mortality and neurologic
      outcomes, and methodological quality were abstracted by 2 independent reviewers.
      DATA SYNTHESIS: Twelve trials met eligibility criteria and were included in the
      analysis. We also performed subanalyses by different hypothermia interventions
      (ie, depth, duration, and rapidity of rewarming after hypothermia) and
      methodological quality. Therapeutic hypothermia was associated with a 19%
      reduction in the risk of death (95% confidence interval [CI], 0.69-0.96) and a
      22% reduction in the risk of poor neurologic outcome (95% CI, 0.63-0.98) compared
      with normothermia. Hypothermia longer than 48 hours was associated with a
      reduction in the risks of death and of poor neurologic outcome (relative risk
      [RR], 0.70; 95% CI, 0.56-0.87 and RR, 0.65; 95% CI, 0.48-0.89, respectively)
      compared with normothermia. Hypothermia to a target temperature between 32
      degrees C and 33 degrees C, a duration of 24 hours, and rewarming within 24 hours
      were all associated with reduced risks of poor neurologic outcome compared with
      normothermia. Assessment of methodological quality did not reveal evidence of
      bias. CONCLUSIONS: Therapeutic hypothermia may reduce the risks of mortality and
      poor neurologic outcome in adults with TBI. Outcomes were influenced, however, by
      depth and duration of hypothermia as well as rate of rewarming (<or=24 hours)
      after discontinuation of hypothermia. Nonetheless, the evidence is not yet
      sufficient to recommend routine use of therapeutic hypothermia for TBI outside of
      research settings.

PMID- 12799409
TI  - Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic
      cirrhosis.
AB  - Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality
      in the United States. Nonalcoholic fatty liver disease (NAFLD) is now recognized
      as the most common cause of cryptogenic cirrhosis. However, the diagnosis of
      cirrhosis in patients with NAFLD appears to be delayed compared with those with
      other chronic liver diseases and thus carries a higher mortality rate. This delay
      in diagnosis is illustrated in our case of a 53-year-old man who presented with
      hepatic hydrothorax and ascites, whose workup revealed cirrhosis due to NAFLD.
      Although a diagnosis of presumed NAFLD can be made noninvasively, a definitive
      diagnosis requires a liver biopsy specimen. A biopsy specimen is also important
      for detecting histologically advanced disease, which may be clinically silent and
      undetected by aminotransferases or diagnostic imaging. Although there are no
      proven treatments, recommendations for patients with NAFLD include avoidance of
      hepatotoxins and aggressive management of associated conditions, such as
      hypertriglyceridemia and type 2 diabetes mellitus.

PMID- 12799410
TI  - Preventing stroke among blacks: the challenges continue.

PMID- 12799411
TI  - Therapeutic hypothermia for severe traumatic brain injury.

PMID- 12799412
TI  - Traumatic brain injury.

PMID- 12799413
TI  - The role of IFNgamma nuclear localization sequence in intracellular function.
AB  - Intracellularly expressed interferon gamma (IFNgamma) has been reported to
      possess biological activity similar to that of IFNgamma added to cells. This
      study addresses the mechanisms for such similar biological effects. Adenoviral
      vectors were used to express a non-secreted form of human IFNgamma or a non
      secreted mutant form in which a previously demonstrated nuclear localization
      sequence (NLS), 128KTGKRKR134, was replaced with alanines at K and R positions.
      With the vector expressing non-secreted wild-type IFNgamma, biological responses
      normally associated with extracellular IFNgamma, such as antiviral activity and
      MHC class I upregulation, were observed, although the mutant IFNgamma did not
      possess biological activity. Intracellular human IFNgamma possessed biological
      activity in mouse L cells, which do not recognize extracellularly added human
      IFNgamma. Thus, the biological activity was not due to leakage of IFNgamma to the
      surroundings and subsequent interaction with the receptor on the cell surface.
      Biological function was associated with activation of STAT1alpha and nuclear
      translocation of IFNgamma, IFNGR1 and STAT1alpha. Immunoprecipitation of cellular
      extracts with antibody to the nuclear transporter NPI-1 showed the formation of a
      complex with IFNgamma-IFNGR1-STAT1alpha. To provide the physiological basis for
      these effects we show that extracellularly added IFNgamma possesses intracellular
      signaling activity that is NLS dependent, as suggested by our previous studies,
      and that this activity occurs via the receptor-mediated endocytosis of IFNgamma.
      The data are consistent with previous observations that the NLS of
      extracellularly added IFNgamma plays a role in IFNgamma signaling.

PMID- 12799414
TI  - LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated
      attachment and ROCK-dependent detachment.
AB  - This study analyzes signaling events initiated through binding of the leukocyte
      integrin LFA-1 to ICAM-1, which leads to T cell attachment, polarization and
      random migration. These events are critically dependent on dynamic changes in the
      acto-myosin cytoskeleton under the regulation of myosin light chain kinase and
      ROCK (Rho kinase). A key finding is that the activity of these two kinases is
      spatially segregated. Myosin light chain kinase (MLCK) must operate at the
      leading edge of the T cell because blocking its activity causes the polarized T
      cell to retract from the front of the cell. These activities are mirrored by
      inhibiting calmodulin, the activator of MLCK. In contrast inhibition of ROCK (and
      RhoA) has the effect of preventing detachment of the T cell trailing edge,
      showing that this kinase operates at the rear of the cell. This compartmentalized
      activity of the two kinases is reflected in their localization within the T cell.
      Myosin light chain kinase is concentrated at the leading edge, overlapping F
      actin, whereas ROCK is more widely distributed in the trailing edge of the T
      cell. Thus these two kinases perform two different functions in the migrating T
      cell, with myosin light chain kinase activity important for attachment and
      movement at the leading edge and ROCK activity required for the detachment of the
      trailing edge. These two actomyosin-dependent processes operate coordinately to
      cause forward migration of a T cell.

PMID- 12799415
TI  - Relationship of DNA double-strand breaks to synapsis in Drosophila.
AB  - The relationship between synaptonemal complex formation (synapsis) and double
      strand break formation (recombination initiation) differs between organisms.
      Although double-strand break creation is required for normal synapsis in
      Saccharomyces cerevisiae and the mouse, it is not necessary for synapsis in
      Drosophila and Caenorhabditis elegans. To investigate the timing of and
      requirements for double-strand break formation during Drosophila meiosis, we used
      an antibody that recognizes a histone modification at double-strand break sites,
      phosphorylation of HIS2AV (gamma-HIS2AV). Our results support the hypothesis that
      double-strand break formation occurs after synapsis. Interestingly, we detected a
      low (10-25% of wildtype) number of gamma-HIS2AV foci in c(3)G mutants, which fail
      to assemble synaptonemal complex, suggesting that there may be both synaptonemal
      complex-dependent and synaptonemal complex-independent mechanisms for generating
      double-strand breaks. Furthermore, mutations in Drosophila Rad54 (okr) and Rad51
      (spnB) homologs cause delayed and prolonged gamma-HIS2AV staining, suggesting
      that double-strand break repair is delayed but not eliminated in these mutants.
      There may also be an interaction between the recruitment of repair proteins and
      phosphorylation.

PMID- 12799416
TI  - Restricted spatial expression of a high-affinity phosphate transporter in potato
      roots.
AB  - Phosphorus deficiency limits plant growth, and high-affinity phosphate
      transporters, of the Pht1 family, facilitate phosphate uptake and translocation.
      The family is subdivided into root specific, phosphate deprivation induced
      members and those also expressed in leaves. An antibody to StPT2, a potato root
      specific transporter, detected two bands (52 kDa and 30 kDa) on western blots of
      root plasma membrane extracts that were most intense in whole extracts from the
      root tip and slightly increased throughout the root in response to phosphate
      depletion. RT-PCR, using StPT2 specific primers, confirmed these findings. Low
      power confocal immunofluorescent images showed StPT2 expression mainly in the
      elongation zone at the root tip. By contrast, a vacuolar pyrophosphatase and a
      plasma membrane ATPase antibody labelled the whole root. High power images
      showed, by comparison with alpha-tubulin, cell wall and plasma membrane ATPase
      labelling, that StPT2 was in the epidermal plasma membrane and restricted to the
      apical surface. This is the first evidence of polar plasma membrane localisation
      of a plant nutrient transporter and is consistent with a role for StPT2 in
      phosphate capture and uptake.

PMID- 12799417
TI  - Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor
      cells of the adult epithelium during amphibian gastrointestinal remodeling.
AB  - In the amphibian gastrointestine during metamorphosis, the primary (larval)
      epithelium undergoes apoptosis. By contrast, a small number of undifferentiated
      cells including stem cells actively proliferate and differentiate into the
      secondary (adult) epithelium that resembles the mammalian counterpart. In the
      present study, to clarify whether Musashi-1 (Msi-1), an RNA-binding protein,
      serves as a marker for progenitor cells of the adult epithelium, we
      chronologically examined Msi-1 expression in the Xenopus laevis gastrointestine
      by using in situ hybridization and immunohistochemistry. Similar expression
      profiles of Msi-1 were observed at both mRNA and protein levels. In both the
      small intestine and the stomach, the transient expression of Msi-1 during
      metamorphosis spatio-temporally correlated well with active proliferation of the
      progenitor cells including stem cells of the adult epithelium but did not with
      apoptosis of the larval epithelium. As the adult progenitor cells differentiated
      into organ-specific epithelial cells after active proliferation, Msi-1 expression
      was rapidly downregulated. Therefore, Msi-1 is useful to identify the adult
      progenitor cells that actively proliferate before final differentiation in the
      amphibian gastrointestine. Furthermore, our culture experiments have shown that
      thyroid hormone (TH) organ-autonomously induces Msi-1 expression only in the
      adult progenitor cells of the X. laevis intestine in vitro as in vivo. However,
      TH could not induce Msi-1 expression in the intestinal epithelium separated from
      the connective tissue, where the adult epithelium never developed. These results
      suggest that Msi-1 expression is upregulated by TH in the adult progenitor cells
      under the control of the connective tissue and plays important roles in their
      maintenance and/or active proliferation during amphibian gastrointestinal
      remodeling.

PMID- 12799418
TI  - DYRK1A accumulates in splicing speckles through a novel targeting signal and
      induces speckle disassembly.
AB  - The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating
      in speckle-like regions. We have found that this punctuated nuclear distribution
      is determined by the contribution of several elements. Although the nuclear
      import is mediated by two distinct nuclear localization signals, one at the N
      terminus and the other located in the linker region, between subdomains X and XI
      of the catalytic domain, the accumulation in speckles that are SC35 positive
      depends on a sequence motif that is located C-terminal to the kinase domain and
      comprises a histidine tail. A similar sequence is also responsible for the
      targeting of cyclin T1. Therefore the histidine-rich region represents a novel
      splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces
      speckle disassembly. Such disassembly is DYRK1A activity specific, since the
      overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a
      chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A
      targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein
      kinase may play a role in regulating the biogenesis of the splicing speckle
      compartment.

PMID- 12799419
TI  - Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial
      alteration.
AB  - Clusterin is a puzzling protein upregulated in many diseased tissues, presented
      as either a survival or a death protein. The role of clusterin might depend on
      the final maturation and localization of the protein, which can be secreted or
      reside inside cells, either after in situ synthesis or uptake of extracellular
      clusterin. We studied the biological effects of intracellular clusterin and
      observed that clusterin forms containing the alpha-chain region strongly
      accumulated in an ubiquitinated form in juxtanuclear aggregates meeting the main
      criterions of aggresomes and leading to profound alterations of the mitochondrial
      network. The viability of cells transfected by intracellular forms of clusterin
      was improved by overexpression of Bcl-2, and caspase inhibition was capable of
      rescuing cells expressing clusterin, which presented an altered mitochondrial
      permeability. We propose that, although it might be an inherently pro-survival
      and anti-apoptotic protein expressed by cells under stress in an attempt to
      protect themselves, clusterin can become highly cytotoxic when accumulated in the
      intracellular compartment. This activity might reconcile the opposite purported
      influences of clusterin on cell survival and explain how clusterin can be
      causally involved in neurodegeneration.

PMID- 12799420
TI  - Differential expression of NO-sensitive guanylyl cyclase subunits during the
      development of rat cerebellar granule cells: regulation via N-methyl-D-aspartate
      receptors.
AB  - In primary cultures of rat cerebellar granule cells with a functional network of
      glutamatergic neurons, the expression pattern of the different subunits of nitric
      oxide (NO)-sensitive guanylyl cyclase changes during cell differentiation. These
      cells express the alpha1, alpha2 and beta1 subunits of NO-sensitive guanylyl
      cyclase and synthesize cyclic guanosine monophosphate (cGMP) in response to
      exogenous or endogenous nitric oxide. In this study, we determined the protein
      content of the alpha1 and beta1 subunits and quantified alpha1, alpha2 and beta1
      mRNA by reverse transcription coupled to a polymerase chain reaction (RT-PCR).
      Expression of the beta1 subunit increased with the degree of cell
      differentiation, although most marked changes occurred at the alpha subunit
      level. In cells freshly isolated from rat pups on postnatal day 7 (P7) the most
      abundant alpha subunit was alpha1, while alpha2 appeared as the predominant
      subunit of this type in cultured cells. N-methyl-D-aspartate (NMDA) receptor
      stimulation in 7- or 14-day-cultured cells led to the upregulation of guanylyl
      cyclase subunit mRNAs; alpha2 mRNA levels undergoing most significant change.
      This enhanced subunit expression was accompanied by an increase in the amount of
      cGMP synthesized in response to NO. Thus, it seems that alpha2 subunits are
      increasingly expressed as granule cells mature. The presence of this subunit in
      the guanylyl cyclase heterodimer facilitates its localization at synaptic
      membranes, where the enzyme acts as a sensor for NO formed by the postsynaptic
      protein 95 (PSD-95)-associated neuronal NO synthase.

PMID- 12799421
TI  - The ectodomain shedding of angiotensin-converting enzyme is independent of its
      localisation in lipid rafts.
AB  - Angiotensin-converting enzyme (ACE), a type I integral membrane protein that
      plays a major role in vasoactive peptide metabolism, is shed from the plasma
      membrane by proteolytic cleavage within the juxtamembrane stalk. To investigate
      whether this shedding is regulated by lateral segregation in cholesterol-rich
      lipid rafts, Chinese hamster ovary cells and human neuroblastoma SH-SY5Y cells
      were transfected with either wild-type ACE (WT-ACE) or a construct with a
      glycosylphosphatidylinositol (GPI) anchor attachment signal replacing the
      transmembrane and cytosolic domains (GPI-ACE). In both cell types, GPI-ACE, but
      not WT-ACE, was sequestered in caveolin or flotillin-enriched lipid rafts and was
      released from the cell surface by treatment with phosphatidylinositol-specific
      phospholipase C. When cells were treated with activators of the protein kinase C
      signalling cascade (phorbol myristate acetate or carbachol) the shedding of GPI
      ACE was stimulated to a similar extent to that of WT-ACE. The release of WT-ACE
      and GPI-ACE from the cells was inhibited in an identical manner by a range of
      hydroxamate-based zinc metalloprotease inhibitors. Disruption of lipid rafts by
      filipin treatment did not alter the shedding of GPI-ACE, and phorbol ester
      treatment did not alter the distribution of WT-ACE or GPI-ACE between raft and
      non-raft membrane compartments. These data clearly show that the protein kinase C
      stimulated shedding of ACE does not require the transmembrane or cytosolic
      regions of the protein, and that sequestration in lipid rafts does not regulate
      the shedding of the protein.

PMID- 12799422
TI  - Tyrosine phosphorylation of the CrkII adaptor protein modulates cell migration.
AB  - CrkII belongs to a family of adaptor proteins that become tyrosine phosphorylated
      after various stimuli. We examined the role of CrkII tyrosine phosphorylation in
      fibronectin-induced cell migration. Overexpression of CrkII inhibited
      dephosphorylation of focal adhesion components such as p130 Crk-associated
      substrate (p130cas) and paxillin by protein tyrosine phosphatase 1B (PTP1B).
      Tyrosine-phosphorylated CrkII was dephosphorylated by PTP1B both in vitro and in
      vivo, showing for the first time that PTP1B directly dephosphorylates CrkII. A
      CrkII mutant in which tyrosine residue 221 was substituted by phenylalanine
      (CrkII-Y221F) could not be tyrosine phosphorylated, and it showed significantly
      increased binding to p130cas and paxillin. Enhanced binding of CrkII to p130cas
      has been reported to promote cell migration. Nonphosphorylated CrkII-Y221F
      promoted HT1080 cell migration on fibronectin, whereas wild-type CrkII did not at
      moderate expression levels. Moreover, co-expression of CrkII and PTP1B promoted
      HT1080 cell migration on fibronectin and retained tyrosine phosphorylation and
      binding of p130cas to CrkII, whereas paxillin tyrosine phosphorylation was
      reduced. These findings support the concepts that CrkII binding activity is
      regulated by tyrosine kinases and phosphatases, and that tyrosine phosphorylation
      of CrkII can downmodulate cell migration mediated by the focal adhesion
      kinase/p130cas pathway.

PMID- 12799423
TI  - Difference in conformational diversity between nucleic acids with a six-membered
      'sugar' unit and natural 'furanose' nucleic acids.
AB  - Natural nucleic acids duplexes formed by Watson-Crick base pairing fold into
      right-handed helices that are classified in two families of secondary structures,
      i.e. the A- and B-form. For a long time, these A and B allomorphic nucleic acids
      have been considered as the 'non plus ultra' of double-stranded nucleic acids
      geometries with the only exception of Z-DNA, a left-handed helix that can be
      adopted by some DNA sequences. The five-membered furanose ring in the sugar
      phosphate backbone of DNA and RNA is the underlying cause of this restriction in
      conformational diversity. A collection of new Watson-Crick duplexes have joined
      the 'original' nucleic acid double helixes at the moment the furanose sugar was
      replaced by different types of six-membered ring systems. The increase in this
      structural and conformational diversity originates from the rigid chair
      conformation of a saturated six-membered ring that determines the orientation of
      the ring substituents with respect to each other. The original A- and B-form
      oligonucleotide duplexes have expanded into a whole family of new structures with
      the potential for selective cross-communication in a parallel or antiparallel
      orientation, opening up a new world for information storage and for molecular
      recognition-directed self-organization.

PMID- 12799424
TI  - Human activation-induced cytidine deaminase causes transcription-dependent,
      strand-biased C to U deaminations.
AB  - Activation-induced cytidine deaminase (AID) is required for the maturation of
      antibodies in higher vertebrates, where it promotes somatic hypermutation (SHM),
      class switch recombination and gene conversion. While it is known that SHM
      requires high levels of transcription of the target genes, it is unclear whether
      this is because AID targets transcribed genes. We show here that the human AID
      promotes C to T mutations in Escherichia coli which are stimulated by
      transcription. The mutations are strand-biased and occur preferentially in the
      non-transcribed strand of the target gene. Human AID purified from E.coli is
      active without prior treatment with a ribonuclease and deaminates cytosines in
      plasmid DNA in vitro. Further, the action of this enzyme is greatly stimulated by
      the transcription of the target gene in a strand-dependent fashion. These results
      confirm the prediction that AID may act directly on DNA and show that it can act
      on transcribing DNA in the absence of specialized DNA structures such as R-loops.
      It suggests that AID may be recruited to variable genes through transcription
      without the assistance of other proteins and that the strand bias in SHM may be
      caused by the preference of AID for the non-transcribed strand.

PMID- 12799425
TI  - Genomic DNA of Nostoc commune (Cyanobacteria) becomes covalently modified during
      long-term (decades) desiccation but is protected from oxidative damage and
      degradation.
AB  - Genomic DNA of Nostoc commune (Cyanobacteria) became covalently modified during
      decades of desiccation. Amplification of gene loci from desiccated cells required
      pretreatment of DNA with N-phenacylthiazolium bromide, a reagent that cleaves DNA
      and protein-linked advanced glycosylation end-products. DNA from 13 year
      desiccated cells did not show any higher levels of the commonly studied
      oxidatively modified DNA damage biomarkers 8-hydroxyguanine, 8-hydroxyadenine and
      5-hydroxyuracil, compared to commercially available calf thymus DNA. Different
      patterns of amplification products were obtained with DNA from
      desiccated/rehydrating cells and a liquid culture derived from the dried
      material, using the same set of primers. In contrast, a reproducible fingerprint
      was obtained, irrespective of time of rehydration of the DNA, using a primer (5'
      GWCWATCGCC-3') based upon a highly iterated palindromic repeat sequence present
      in the genome. In vitro, the desiccation of cccDNA led to loss of supercoiling,
      aggregation, loss of resolution during agarose gel electrophoresis and loss of
      transformation and transfection efficiency. These changes were minimized when DNA
      was desiccated and stored in the presence of trehalose, a non-reducing
      disaccharide present in Nostoc colonies. The response of the N.commune genome to
      desiccation is different from the response of the genomes of cyanobacteria and
      Deinococcus radiodurans to ionizing radiation.

PMID- 12799426
TI  - Bimodal interaction between replication-protein A and Dna2 is critical for Dna2
      function both in vivo and in vitro.
AB  - We have previously shown that replication- protein A (RPA), the heterotrimeric
      single-stranded DNA binding protein of eukaryotes, plays a role in Okazaki
      fragment processing by acting as a molecular switch between the two
      endonucleases, Dna2 and Fen1, to ensure the complete removal of primer RNAs in
      Saccharomyces cerevisiae. The stimulation of Dna2 endonuclease activity by RPA
      requires direct protein-protein interaction. In this report we have analyzed
      genetically and biochemically the interaction of Dna2 with RPA. RFA1, the gene
      encoding the large subunit of RPA, displayed allele-specific interactions with
      DNA2 that included synthetic lethality and intergenic complementation. In
      addition, we identified physical and functional interactions between these
      proteins and found that RPA binds Dna2 predominantly through its large subunit,
      Rpa1. Consistent with the mapping of synthetic lethal mutations, robust
      interaction localizes to the C-termini of these proteins. Moreover, the N
      terminal domains of Dna2 and Rpa1 appear to be important for a functional
      interaction because the N-terminal domain of RPA1 was required to maximally
      stimulate Dna2 endonuclease activity. We propose that a bimodal interaction of
      Dna2 with Rpa1 is important for Dna2 function both in vivo and in vitro. The
      relevance of each interaction with respect to the function of the Dna2
      endonuclease activity is discussed.

PMID- 12799427
TI  - Identification of novel co-repressor molecules for Interferon Regulatory Factor
      2.
AB  - We have identified two novel proteins that interact specifically with the C
      terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These
      proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2,
      the latter having two splicing isoforms, A and B), are nuclear proteins, and have
      the properties of IRF-2-dependent transcriptional co-repressors that can inhibit
      both enhancer-activated and basal transcription in a manner that is not dependent
      upon histone deacetylation. IRF-2BP1 and IRF-2BP2A/B contain an N-terminal zinc
      finger and a C-terminal RING finger domain of the C3HC4 subclass, but show no
      homology to other known transcriptional regulators; they therefore define a new
      family of co- repressor proteins. An alternatively spliced form of IRF-2 that
      lacks two amino acids (valines 177 and 178) in the central portion of the protein
      (IRF-2[S]) cannot bind to these co-repressors and cannot mediate repression
      despite having the same C- terminal repression domain as IRF-2, suggesting that
      the relative conformation of the DNA binding domain and the C-terminal region of
      IRF-2 is crucial for transcriptional repression.

PMID- 12799428
TI  - A DNA Spiegelmer to staphylococcal enterotoxin B.
AB  - Bacterial staphylococcal enterotoxin B is involved in several severe disease
      patterns and it was therefore used as a target for the generation of biologically
      stable mirror-image oligonucleotide ligands, so called Spiegelmers. The toxin is
      a 28 kDa protein consisting of 239 amino acids. Since the full-length protein is
      not accessible to chemical peptide synthesis, a stable domain of 25 amino acids
      was identified as a suitable selection target. DNA in vitro selection experiments
      were carried out against the equivalent mirror-image D-peptide domain resulting
      in high affinity D-DNA aptamers. As expected, the corresponding enantiomeric L
      DNA Spiegelmer showed comparable binding characteristics to the L-peptide domain.
      Moreover, the Spiegelmer bound the whole protein target with only slightly
      reduced affinity. Dissociation constants of both peptide-oligonucleotide
      complexes were measured in the range of 200 nM, whereas the Spiegelmer binding to
      the full-length protein was determined at approximately 420 nM. These data
      demonstrate the possibility to identify Spiegelmers against large protein targets
      by a domain approach.

PMID- 12799429
TI  - Yeast Ume6p repressor permits activator binding but restricts TBP binding at the
      HOP1 promoter.
AB  - Ume6p plays essential roles in the regulation of early meiotic genes in
      Saccharomyces cerevisiae. Ume6p exerts repression via recruitment of the Sin3p
      Rpd3p histone deacetylase and Isw2p chromatin remodeling complexes. The
      transcriptional step that is ultimately inhibited by Ume6p is unknown. Here, in
      vivo footprinting shows that transcriptional activators Hap1p and Abf1p occupy
      upstream sites in repressed and derepressed promoters. In contrast, chromatin
      immunoprecipitation shows that TATA box-binding protein (TBP)- promoter binding
      is reduced upon repression of HOP1. Fusion of TBP to a zinc cluster DNA binding
      domain relieves repression at a HOP1 promoter modified to include the zinc
      cluster target site. We suggest that TBP binding is inhibited through chromatin
      modification by the Sin3p-Rpd3p and Isw2p complexes recruited by Ume6p.

PMID- 12799430
TI  - The C-terminal domain of Escherichia coli MutY is involved in DNA binding and
      glycosylase activities.
AB  - Escherichia coli MutY is an adenine and a weak guanine DNA glycosylase involved
      in reducing mutagenic effects of 7,8-dihydro-8-oxo-guanine (8-oxoG). The C
      terminal domain of MutY is required for 8-oxoG recognition and is critical for
      mutation avoidance of oxidative damage. To determine which residues of this
      domain are involved in 8-oxoG recognition, we constructed four MutY mutants based
      on similarities to MutT, which hydrolyzes specifically 8-oxo-dGTP to 8-oxo-dGMP.
      F294A-MutY has a slightly reduced binding affinity to A/G mismatch but has a
      severe defect in A/8-oxoG binding at 20 degrees C. The catalytic activity of
      F294A-MutY is much weaker than that of the wild-type MutY. The DNA binding
      activity of R249A-MutY is comparable to that of the wild-type enzyme but the
      catalytic activity is reduced with both A/G and A/8-oxoG mismatches. The
      biochemical activities of F261A-MutY are nearly similar to those of the wild-type
      enzyme. The solubility of P262A-MutY was improved as a fusion protein containing
      streptococcal protein G (GB1 domain) at its N-terminus. The binding of GB1-P262A
      MutY with both A/G and A/8-oxoG mismatches are slightly weaker than those of the
      wild-type protein. The catalytic activity of GB1-P262A-MutY is weaker than that
      of the wild-type enzyme at lower enzyme concentrations. Importantly, all four
      mutants can complement mutY mutants in vivo when expressed at high levels;
      however, F294A, R249A and P262A, but not F261A, are partially defective in vivo
      when they are expressed at low levels. These results strongly support that the C
      terminal domain of MutY is involved not only in 8-oxoG recognition, but also
      affects the binding and catalytic activities toward A/G mismatches.

PMID- 12799431
TI  - Single-chain Tet transregulators.
AB  - We demonstrate here that the Tet repressor (TetR), a dimeric allosterical
      regulatory protein, can be converted to a fully functional monomer when connected
      by a 29 amino acid linker. TetR-based transregulators are widely used to regulate
      gene expression in eukaryotes. They can be fused to form single-chain (sc) Tet
      transregulators with two TetR moieties and one eukaryotic regulatory domain. Sc
      variants of transactivator and transsilencer exhibit the same regulatory
      properties as their respective dimeric counterparts in human cell lines. In
      particular, the reverse 'tet-on' phenotype of rtTA variants is also present in
      the sc variants. Coexpression of a reverse transactivator and sc transsilencer
      leads to reduced background expression and shows full activation upon induction.
      The data demonstrate that sc Tet transregulators exhibit the phenotype of their
      respective dimers and lack functional interference when coexpressed in the same
      cell.

PMID- 12799432
TI  - OligoArray 2.0: design of oligonucleotide probes for DNA microarrays using a
      thermodynamic approach.
AB  - There is a substantial interest in implementing bioinformatics technologies that
      allow the design of oligonucleotides to support the development of microarrays
      made from short synthetic DNA fragments spotted or in situ synthesized on slides.
      Ideally, such oligonucleotides should be totally specific to their respective
      targets to avoid any cross-hybridization and should not form stable secondary
      structures that may interfere with the labeled probes during hybridization. We
      have developed OligoArray 2.0, a program that designs specific oligonucleotides
      at the genomic scale. It uses a thermodynamic approach to predict secondary
      structures and to calculate the specificity of targets on chips for a unique
      probe in a mixture of labeled probes. Furthermore, OligoArray 2.0 can adjust the
      oligonucleotide length, according to user input, to fit a narrow T(m) range
      compatible with hybridization requirements. Combined with on chip oligonucleotide
      synthesis, this program makes it feasible to perform expression analysis on a
      genomic scale for any organism for which the genome sequence is known. This is
      without relying on cDNA or oligonucleotide libraries. OligoArray 2.0 was used to
      design 75 764 oligonucleotides representing 26 140 transcripts from Arabidopsis
      thaliana. Among this set, we provide at least one specific oligonucleotide for
      93% of these transcripts.

PMID- 12799434
TI  - The nicking homing endonuclease I-BasI is encoded by a group I intron in the DNA
      polymerase gene of the Bacillus thuringiensis phage Bastille.
AB  - Here we describe the discovery of a group I intron in the DNA polymerase gene of
      Bacillus thuringiensis phage Bastille. Although the intron insertion site is
      identical to that of the Bacillus subtilis phages SPO1 and SP82 introns, the
      Bastille intron differs from them substantially in primary and secondary
      structure. Like the SPO1 and SP82 introns, the Bastille intron encodes a nicking
      DNA endonuclease of the H-N-H family, I-BasI, with a cleavage site identical to
      that of the SPO1-encoded enzyme I-HmuI. Unlike I-HmuI, which nicks both intron
      minus and intron-plus DNA, I-BasI cleaves only intron-minus alleles, which is a
      characteristic of typical homing endonucleases. Interestingly, the C-terminal
      portions of these H-N-H phage endonucleases contain a conserved sequence motif,
      the intron-encoded endonuclease repeat motif (IENR1) that also has been found in
      endonucleases of the GIY-YIG family, and which likely comprises a small DNA
      binding module with a globular betabetaalphaalphabeta fold, suggestive of module
      shuffling between different homing endonuclease families.

PMID- 12799433
TI  - Specific interaction of heterogeneous nuclear ribonucleoprotein A1 with the -219T
      allelic form modulates APOE promoter activity.
AB  - The polymorphic -219T/G variant in the APOE promoter has been associated with
      variations in basal transcriptional activity as well as with the risk of
      developing Alzheimer's disease, myocardial infarction and early-onset coronary
      heart disease. The molecular mechanisms underlying these effects are presently
      unknown. In this report, we show that nuclear extracts from Jurkat cells form a T
      specific complex with a motif including the -219 site within the APOE promoter.
      By DNA-affinity chromatography and mass spectrometry, the human heterogeneous
      nuclear ribonucleoprotein hnRNPA1(A1) was identified as one component of the
      complex. In vitro binding analysis indicated that a fragment of A1 had a marked
      binding specificity for the T form. Interaction of A1 with this region is driven
      by an adjacent telomeric-like sequence; however, the presence of G, but not T, at
      -219 position inhibited this interaction. The differences in transcriptional
      activity between the -219T and -219G promoter allelic forms correlated with the
      expression levels of A1 in several cell lines; also, over-expression of A1
      increased the activity of the T form relative to that of the G form. These
      results indicate that A1 transactivates APOE promoter activity by direct and
      specific interaction with the -219T site.

PMID- 12799435
TI  - DNA sequence representation without degeneracy.
AB  - Graphical representation of DNA sequence provides a simple way of viewing,
      sorting and comparing various gene structures. A new two-dimensional graphical
      representation method using a two- quadrant Cartesian coordinates system has been
      derived for mathematical denotation of DNA sequence. The two-dimensional graphic
      representation resolves sequences' degeneracy and is mathematically proven to
      eliminate circuit formation. Given x-projection and y-projection of any point on
      the graphical representation, the number of A, G, C and T from the beginning of
      the sequence to that point could be found. Compared with previous methods, this
      graphical representation is more in-line with the conventional recognition of
      linear sequences by molecular biologists, and also provides a metaphor in two
      dimensions for local and global DNA sequence comparison.

PMID- 12799436
TI  - Sequence analysis of three mitochondrial DNA molecules reveals interesting
      differences among Saccharomyces yeasts.
AB  - The complete sequences of mitochondrial DNA (mtDNA) from the two budding yeasts
      Saccharomyces castellii and Saccharomyces servazzii, consisting of 25 753 and 30
      782 bp, respectively, were analysed and compared to Saccharomyces cerevisiae
      mtDNA. While some of the traits are very similar among Saccharomyces yeasts,
      others have highly diverged. The two mtDNAs are much more compact than that of
      S.cerevisiae and contain fewer introns and intergenic sequences, although they
      have almost the same coding potential. A few genes contain group I introns, but
      group II introns, otherwise found in S.cerevisiae mtDNA, are not present.
      Surprisingly, four genes (ATP6, COX2, COX3 and COB) in the mtDNA of S.servazzii
      contain, in total, five +1 frameshifts. mtDNAs of S.castellii, S.servazzii and
      S.cerevisiae contain all genes on the same strand, except for one tRNA gene. On
      the other hand, the gene order is very different. Several gene rearrangements
      have taken place upon separation of the Saccharomyces lineages, and even a part
      of the transcription units have not been preserved. It seems that the
      mechanism(s) involved in the generation of the rearrangements has had to ensure
      that all genes stayed encoded by the same DNA strand.

PMID- 12799437
TI  - Cc RNase: the Ceratitis capitata ortholog of a novel highly conserved protein
      family in metazoans.
AB  - Complementary DNA encoding a protein, designated Cc RNase, was isolated from the
      insect Ceratitis capitata. Deduced amino acid sequence analysis demonstrates that
      the Cc RNase has strong sequence homology with other uncharacterized proteins
      predicted from EST sequences belonging to different animal species, therefore
      defining a new protein family, which is conserved from Caenorhabditis elegans to
      humans. Phylogenetic analysis data in addition to extensive homolog searches in
      all available complete genomes suggested that all family members are true
      orthologs. Proteins belonging to this family are composed of 95-101 amino acids.
      The C.capitata orthologous protein was expressed in Escherichia coli. Despite the
      fact that the amino acid sequence of Cc RNase does not share any significant
      similarities with other known ribonucleases, our data give strong evidence in
      support of the assignment of enzymatic activity to the recombinant protein. The
      expressed molecule exhibits ribonucleolytic activity against poly(C) and poly(U)
      synthetic substrates, as well as rRNA. It is also demonstrated that expression of
      Cc RNase in E.coli inhibits growth of the host cells.

PMID- 12799438
TI  - Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F
      Rb-HDAC-dependent and -independent pathways.
AB  - Abnormal expression of Dnmt1 in vivo induces cellular alterations such as
      transformation, and an increase in Dnmt1 mRNA plays a causal role in c-fos-, ras-
      and SV40 large T antigen-induced transformation of fibroblasts in vitro. Here, we
      have investigated the regulation of Dnmt1 transcription. We identified the
      promoter region and major transcription start sites of mouse Dnmt1 and found two
      important cis-elements within the core promoter region. One is an E2F binding
      site, and the other is a binding site for an as yet unidentified factor. Point
      mutations in the two cis-elements decreased promoter activity in both non
      transformed and transformed cells. Thus, both sites play a critical role in
      regulation of Dnmt1 transcription in proliferating cells. Treatment with
      trichostatin A, a specific inhibitor of histone deacetylase, increased Dnmt1
      promoter activity in G0/G1-arrested NIH 3T3 cells. Furthermore, the decrease in
      promoter activity induced by expression of E2F-1 and Rb was reversed by
      trichostatin A treatment of Saos-2 cells. Taken together, these data indicate
      that transcription of Dnmt1 is regulated in a complex fashion by E2F and other
      transcription factors through E2F-Rb-HDAC-dependent and -independent pathways.
      These findings suggest that Dnmt1 is a target gene of these pathways in cell
      proliferation, cell transformation and tumorigenesis.

PMID- 12799439
TI  - The SV40 T antigen modulates CBP histone acetyltransferase activity.
AB  - Histone acetyltransferases (HATs) play a key role in transcription control, cell
      proliferation and differentiation by modulating chromatin structure; however,
      little is known about their own regulation. Here we show that expression of the
      viral oncoprotein SV40 T antigen increases histone acetylation and global
      cellular HAT activities. In addition, it enhances CREB-binding protein HAT
      activity and modulates its transcriptional activity. Finally, we show that
      inhibition of cellular histone deacetylases by trichostatin A increases the SV40
      infectivity rate. These findings highlight the importance of histone acetylation
      in the regulation of the cell cycle by oncoviral proteins.

PMID- 12799440
TI  - Histone deacetylase inhibition is associated with transcriptional repression of
      the Hmga2 gene.
AB  - The high-mobility-group A2 protein (HMGA2) plays important functional roles in
      transcriptional regulation, DNA replication and chromatin structure. In this
      study, the effect of histone deacetylase inhibition on the transcriptional
      activity of the Hmga2 gene was investigated in vivo both at the endogenous gene
      level and in a variety of cell lines using transiently transfected promoter
      constructs. Trichostatin A (TSA) repressed both transfected murine and human
      Hmga2 promoter constructs 3-8-fold in NIH3T3, F9 and HeLa cells. Steady-state
      Hmga2 mRNA levels in NIH3T3 cells decreased 4-5-fold following TSA treatment,
      while pre- treatment of NIH3T3 cells with the transcriptional inhibitor,
      actinomycin D, completely blocked TSA mediated repression of the Hmga2 gene.
      Cross-linked chromatin immunoprecipitation (X-ChIP) analysis revealed a 5-6-fold
      decrease in endogenous Hmga2 promoter bound Sp1 and Sp3 proteins following TSA
      treatment in parallel with observed loss of acetylated histone H3 and H4. In
      addition, the poly-pyrimidine-tract-binding protein (PTB) was observed to bind to
      the Hmga2 promoter in both TSA treated and untreated NIH3T3 cells. Together,
      these results suggest TSA treatment leads to a decrease in Hmga2 gene
      transcription, and a significant decrease in promoter bound Sp1, Sp3 and
      acetylated histones H3 and H4.

PMID- 12799441
TI  - Inter-strand photoproducts are produced in high yield within A-DNA exposed to UVC
      radiation.
AB  - Far-UV irradiation of DNA leads to the dimerization of pyrimidine bases,
      resulting in the formation of cyclobutane type dimers and (6-4) photoproducts. In
      the dry state, an additional thymine dimeric photolesion, the spore photoproduct,
      is also generated. While most photoproducts are expected to be produced between
      adjacent pyrimidines, little attention has been paid to lesions involving bases
      located on different DNA strands. Using HPLC- mass spectrometry analysis of
      enzymatically digested DNA, we observed that, in the dry state, inter-strand
      dimeric photoproducts represented 30% of the total yield of dimeric thymine
      lesions. The major inter-strand damage was found to be the spore photoproduct.
      Formation of inter-strand lesions in significant yield could be obtained in
      solution upon modification of the DNA conformation as the result of the addition
      of large amounts of ethanol. In both cases, DNA is in the A-form, which is
      characterized by a high compaction, likely to favor inter-strand photoreactions.
      Since the latter DNA conformation is also predominant in bacterial spores, the
      formation and repair of dimeric photoproducts involving thymine bases located on
      different DNA strands may thus be relevant in terms of deleterious effects of UV
      radiation to the latter microorganisms.

PMID- 12799442
TI  - Inactivation of the nod box distal half-site allows tetrameric NodD to activate
      nodA transcription in an inducer-independent manner.
AB  - In Rhizobium leguminosarum, NodD can activate nodA transcription in response to
      inducer flavonoids. Here, we show that the inducible nodA promoter contains an
      intrinsic part through which NodD can activate nodA transcription in an inducer
      independent manner. Evidence was provided that NodD binds to target DNA through
      anchoring the two half-sites of the nod box as a tetramer. An imperfect inverted
      repeat AT-N10-GAT was found in each half-site and is critical for NodD binding.
      Mutation of the inverted repeat of the nod box distal half-site allowed NodD to
      activate nodA transcription in an inducer-independent manner in vivo, and to
      modulate the DNA bending of the NodD-nod box complex in the absence of inducer in
      vitro.

PMID- 12799444
TI  - Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like family.
AB  - The interferon-induced 2'-5'-oligoadenylate synthetases (OAS) are important for
      the antiviral activity of interferons. The human and murine OAS gene families
      each contain four genes: OAS1, OAS2, OAS3 and OASL, all having one or more
      conserved OAS units composed of five translated exons. The OASL gene has both an
      OAS unit and a C-terminus of two ubiquitin-like repeats. In this study, we
      demonstrate that murine Oasl1 protein is inactive while murine Oasl2 is active as
      an OAS. Further more, murine Oasl2 requires double-stranded RNA as co-factor. The
      affinity of murine Oasl2 for the double-stranded RNA activator is higher than
      that of human OAS1 (p42 isoform). We propose a model for the evolutionary origin
      of the murine Oasl1 and Oasl2 genes. The identification of a human orthologue
      (hOASL2) to the murine Oasl2 gene establishes that the OASL gene was duplicated
      prior to the radiation of the rodent and primate groups. We suggest that murine
      Oasl2, which has both enzymatic activity and a ubiquitin-like domain, is a
      functional intermediate between the active OAS species and the inactive human
      OASL1/murine Oasl1 proteins. In addition, we propose that murine Oasl1 appears to
      have gained a hitherto uncharacterized function independent of 2'-5'-linked
      oligoadenylate synthesis.

PMID- 12799443
TI  - The Upf-dependent decay of wild-type PPR1 mRNA depends on its 5'-UTR and first 92
      ORF nucleotides.
AB  - mRNAs containing premature translation termination codons (nonsense mRNAs) are
      targeted for deadenylation-independent degradation in a mechanism that depends on
      Upf1p, Upf2p and Upf3p. This decay pathway is often called nonsense- mediated
      mRNA decay (NMD). Nonsense mRNAs are decapped by Dcp1p and then degraded 5' to 3'
      by Xrn1p. In the yeast Saccharomyces cerevisiae, a significant number of wild
      type mRNAs accumulate in upf mutants. Wild-type PPR1 mRNA is one of these mRNAs.
      Here we show that PPR1 mRNA degradation depends on the Upf proteins, Dcp1p, Xrn1p
      and Hrp1p. We have mapped an Upf1p-dependent destabilizing element to a region
      located within the 5'-UTR and the first 92 bases of the PPR1 ORF. This element
      targets PPR1 mRNA for Upf-dependent decay by a novel mechanism.

PMID- 12799445
TI  - Ribosomes stalling on uORF1 in the Xenopus Cx41 5' UTR inhibit downstream
      translation initiation.
AB  - Translation of Xenopus laevis Connexin41 mRNA is strongly controlled by the three
      upstream open reading frames (uORFs) in its 5' untranslated region. Mutation of
      uAUG1 into AAG induced a 100-fold increase in translation of a green fluorescent
      protein (GFP) reporter ORF. The termination codon of uORF1 was mutated and the
      uORF was linked in-frame with the GFP ORF, enabling visualisation of initiation
      at uAUG1 by synthesis of an elongated GFP form. Unexpectedly, hardly any
      elongated GFP was made, suggesting that translation of uORF1 in wild-type mRNA
      causes constraining of the entry of 40S ribosomal subunits upstream of uORF1. A
      rare leucine codon, the third codon of uORF1, contributed to the slow translation
      and thus to slow scanning. Replacement of the rare leucine codon in uORF1 with a
      common leucine codon stimulated GFP translation. Remarkably, the rare leucine
      codon, the termination codon of uORF1, uAUG2 and uAUG3 all improved recognition
      of uAUG1. Apparently, the block formed by a stalled ribosome on any element in
      uORF1 prevented the landing of new ribosomal subunits next to the cap and
      therefore downregulated GFP translation.

PMID- 12799446
TI  - Comparison of different antisense strategies in mammalian cells using locked
      nucleic acids, 2'-O-methyl RNA, phosphorothioates and small interfering RNA.
AB  - Locked nucleic acids (LNAs) and double-stranded small interfering RNAs (siRNAs)
      are rather new promising antisense molecules for cell culture and in vivo
      applications. Here, we compare LNA-DNA-LNA gapmer oligonucleotides and siRNAs
      with a phosphorothioate and a chimeric 2'-O-methyl RNA-DNA gapmer with respect to
      their capacities to knock down the expression of the vanilloid receptor subtype 1
      (VR1). LNA-DNA-LNA gapmers with four or five LNAs on either side and a central
      stretch of 10 or 8 DNA monomers in the center were found to be active gapmers
      that inhibit gene expression. A comparative co-transfection study showed that
      siRNA is the most potent inhibitor of VR1-green fluorescent protein (GFP)
      expression. A specific inhibition was observed with an estimated IC50 of 0.06 nM.
      An LNA gapmer was found to be the most efficient single-stranded antisense
      oligonucleotide, with an IC50 of 0.4 nM being 175-fold lower than that of
      commonly used phosphorothioates (IC50 approximately 70 nM). In contrast, the
      efficiency of a 2'-O-methyl-modified oligonucleotide (IC50 approximately 220 nM)
      was 3-fold lower compared with the phosphorothioate. The high potency of siRNAs
      and chimeric LNA-DNA oligonucleotides make them valuable candidates for cell
      culture and in vivo applications targeting the VR1 mRNA.

PMID- 12799447
TI  - Alternatively spliced isoforms of the human constitutive androstane receptor.
AB  - The nuclear receptor CAR (NR1I3) regulates transcription of genes encoding
      xenobiotic- and steroid-metabolizing enzymes. Regulatory processes that are
      mediated by CAR are modulated by a structurally diverse array of chemicals
      including common pharmaceutical and environmental agents. Here we describe four
      in-frame splice variants of the human CAR receptor gene. The variant mRNA splice
      transcripts were expressed in all human livers evaluated. Molecular modeling of
      the splice variant proteins predicts that the structural effects are localized
      within the receptor's ligand-binding domain. Assays to assess function indicate
      that the variant proteins, when compared with the reference protein isoform,
      exhibit compromised activities with respect to DNA binding, transcriptional
      activation and coactivator recruitment.

PMID- 12799448
TI  - Canonical nucleosides can be utilized by T4 DNA ligase as universal template
      bases at ligation junctions.
AB  - T4 DNA ligase catalyzes the template-dependent ligation of DNA. Using T4 DNA
      ligase under specific experimental conditions, we demonstrate that each of the
      four canonical nucleosides, centrally located on a template molecule such that
      they flank the site of ligation, can direct the ligation of nucleic acids
      regardless of the identity of the terminal nucleosides being covalently joined.
      This universal templating capability extends to those positions adjacent to the
      ligation junction. This is the first report, irrespective of the ligation method
      used or the identity of the template nucleosides (including analogs), which shows
      that nucleosides can act essentially as universal templates at ligation junctions
      in vitro. The canonical nucleosides do, however, differ in their ability to
      template sequence- independent ligations, with thymidine and guanosine being
      equally effective, yet more effective than adenosine and cytidine. Results
      indicate that hybridization strength surrounding the ligation junction is an
      important factor. The implications of this previously undiscovered property of T4
      DNA ligase with canonical nucleosides are discussed.

PMID- 12799449
TI  - N-terminus of hMLH1 confers interaction of hMutLalpha and hMutLbeta with
      hMutSalpha.
AB  - Mismatch repair is a highly conserved system that ensures replication fidelity by
      repairing mispairs after DNA synthesis. In humans, the two protein heterodimers
      hMutSalpha (hMSH2-hMSH6) and hMutLalpha (hMLH1-hPMS2) constitute the centre of
      the repair reaction. After recognising a DNA replication error, hMutSalpha
      recruits hMutLalpha, which then is thought to transduce the repair signal to the
      excision machinery. We have expressed an ATPase mutant of hMutLalpha as well as
      its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by
      examination of their interaction properties with hMutSalpha using a novel
      interaction assay. We show that, although the interaction requires ATP,
      hMutLalpha does not need to hydrolyse this nucleotide to join hMutSalpha on DNA,
      suggesting that ATP hydrolysis by hMutLalpha happens downstream of complex
      formation. The analysis of the individual subunits of hMutLalpha demonstrated
      that the hMutSalpha-hMutLalpha interaction is predominantly conferred by hMLH1.
      Further experiments revealed that only the N-terminus of hMLH1 confers this
      interaction. In contrast, only the C-terminus stabilised and co
      immunoprecipitated hPMS2 when both proteins were co-expressed in 293T cells,
      indicating that dimerisation and stabilisation are mediated by the C-terminal
      part of hMLH1. We also examined another human homologue of bacterial MutL,
      hMutLbeta (hMLH1-hPMS1). We show that hMutLbeta interacts as efficiently with
      hMutSalpha as hMutLalpha, and that it predominantly binds to hMutSalpha via hMLH1
      as well.

PMID- 12799450
TI  - Peptidyl-tRNA hydrolase from Sulfolobus solfataricus.
AB  - An enzyme capable of liberating functional tRNA(Lys) from Escherichia coli
      diacetyl-lysyl-tRNA(Lys) was purified from the archae Sulfolobus solfataricus.
      Contrasting with the specificity of peptidyl- tRNA hydrolase (PTH) from E.coli,
      the S.solfataricus enzyme readily accepts E.coli formyl-methionyl-tRNA(fMet) as a
      substrate. N-terminal sequencing of this enzyme identifies a gene that has
      homologs in the whole archaeal kingdom. Involvement of this gene (SS00175) in the
      recycling of peptidyl-tRNA is supported by its capacity to complement an E.coli
      strain lacking PTH activity. The archaeal gene, the product of which appears
      markedly different from bacterial PTHs, also has homologs in all the available
      eukaryal genomes. Since most of the eukaryotes already display a bacterial-like
      PTH gene, this observation suggests the occurrence in many eukaryotes of two
      distinct PTH activities, either of a bacterial or of an archaeal type. Indeed,
      the bacterial- and archaeal-like genes encoding the two full-length PTHs of
      Saccharomyces cerevisiae, YHR189w and YBL057c, respectively, can each rescue the
      growth of an E.coli strain lacking endogeneous PTH. In vitro assays confirm that
      the two enzymes ensure the recycling of tRNA(Lys) from diacetyl-lysyl-tRNA(Lys).
      Finally, the growth of yeast cells in which either YHR189w or YBL057c has been
      disrupted was compared under various culture conditions. Evidence is presented
      that YHR189w, the gene encoding a bacterial-like PTH, should be involved in
      mitochondrial function.

PMID- 12799451
TI  - The acidic C-terminal domain and A-box of HMGB-1 regulates p53-mediated
      transcription.
AB  - p53 function is modulated by several covalent and non-covalent modifiers. The
      architectural DNA- binding protein, High Mobility Group protein B-1 is a unique
      activator of p53. HMGB-1 protein is structured into two HMG-box domains, namely A
      box and B-box, connected to a long highly acidic C-terminal domain. Here we
      report that both the C-terminal domain and A-box of HMGB-1 are critical for
      stimulation of p53-mediated DNA binding to its cognate site. Though deletion of
      these domains showed minimal effect in activation of p53-mediated transcription
      from the DNA template as compared to full-length HMGB-1, truncation of both the
      domains indeed showed significant reduction of transcriptional activation from
      the chromatin template as observed in DNA binding. Using transient transfection
      assays we showed that the C-terminal acidic domain and A-box of HMGB-1 are
      critical for the enhancement of the p53-mediated transactivation in vivo.
      Furthermore, the C-terminal domain and A-box deleted HMGB-1 could not activate
      p53-dependent apoptosis above the basal level. In conclusion, these results
      elucidate the role of acidic C-terminal domain and A-box of HMGB-1 in p53
      mediated transcriptional activation and its further downstream effect.

PMID- 12799452
TI  - Stimulation of Tat-independent transcriptional processivity from the HIV-1 LTR
      promoter by matrix attachment regions.
AB  - The chromatin environment and the sites of integration in the host genome are
      critical determinants of human immunodeficiency virus (HIV) transcription and
      replication. Depending on the chromosomal location of provirus integration within
      the genome, HIV-1 long terminal repeat (LTR)-mediated transcription may vary from
      0- to 70-fold. Cis-elements such as topoisomerase II cleavage sites, Alu repeats
      and matrix attachment regions (MARs) are thought to be targets for retroviral
      integration. Here we show that a novel MAR sequence from the T-cell receptor beta
      locus (MARbeta) and the IgH MAR mediate transcriptional augmentation when placed
      upstream of the HIV-1 LTR promoter. The effect of transcriptional augmentation is
      seen in both transient and stable transfection, indicating its effect even upon
      integration in the genome. MAR-mediated transcriptional elevation is independent
      of Tat, and occurs synergistically in the presence of Tat. Further, we show that
      MAR-mediated transcriptional elevation is specific to the HIV-1 LTR and the
      Moloney murine leukemia virus LTR promoter. In a transient transfection assay
      using over-expressed IkappaB, the inhibitor of NF-kappaB, we show that MAR
      induced processive transcription is NF-kappaB dependent, signifying the role of
      local enhancers within the LTR promoter. Furthermore, by RNase protection
      experiments using proximal and distal probes, we show that MAR-mediated
      transcriptional upregulation is more prominent at the distal rather than the
      proximal end, thus indicating the potential role of MARs in promoting elongation.

PMID- 12799454
TI  - Triplex formation with 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) having C3'
      endo conformation at physiological pH.
AB  - Antigenes, which are substances that inhibit gene expression by binding to double
      stranded DNA (dsDNA) in a sequence-specific manner, are currently sought for the
      treatment of various gene-related diseases. As such antigenes, we developed new
      nuclease-resistant oligopyrimidine nucleotides that are partially modified with
      2'-O,4'-C-ethylene nucleic acids (ENA), which are constrained in the C3'-endo
      conformation and can form a triplex with dsDNA at physiological pH. It was found
      that these oligonucleotides formed triplexes similarly to those partially
      modified with 2'-O,4'-C-methylene nucleic acids (2',4'-BNA or LNA), as determined
      by UV melting analyses, electromobility shift assays, CD spectral analyses and
      restriction enzyme inhibition assays. In our studies, oligonucleotides fully
      modified with ENA have delta torsion angle values that are marginally higher than
      those of 2',4'-BNA/LNA. ENA oligonucleotides present in 10-fold the amount of
      dsDNA were found to be favorable in forming triplexes. These results provide
      useful information for the future design of triplex-forming oligonucleotides
      fully modified with such nucleic acids constrained in the C3'-endo conformation
      considering that oligonucleotides fully modified with 2',4'-BNA/LNA do not form
      triplexes.

PMID- 12799453
TI  - Nuclear matrix association of the human beta-globin locus utilizing a novel
      approach to quantitative real-time PCR.
AB  - The human beta-globin locus is home to five genes that are regulated in a tissue
      specific and developmental stage-specific manner. While the exact mode of
      expression remains somewhat enigmatic, a significant effort has been focused at
      the locus control region (LCR). The LCR is marked by five DNase I-hypersensitive
      sites (HS) approximately 15 kb upstream of the epsilon-globin gene. Nuclear
      matrix-associated regions (MARs) organize chromatin into functional domains and
      at least one of the HS appears bound to the nuclear matrix. We have employed an
      in vivo based PCR MAR assay to investigate the role of MAR-mediated regulation of
      the beta-globin locus. This was facilitated with a novel reaction efficiency
      based quantitative real-time PCR analysis software tool, Target Analysis
      Quantification. Using a log-linear regression strategy, discordances were
      eliminated. This allowed us to reliably estimate the relative amount of initial
      template associated with the nuclear matrix at 15 unique regions spanning the
      beta-globin locus in both non-expressing and expressing cell lines. A dynamic
      association dependent on expression status was revealed both at the LCR/5'HS
      region and within the second intron of the beta-globin gene. These results
      provide the first evidence that nuclear matrix association dynamically mediates
      the looping of the beta-globin locus to achieve transcriptional control.

PMID- 12799455
TI  - DNA binding properties of the adenovirus DNA replication priming protein pTP.
AB  - The precursor terminal protein pTP is the primer for the initiation of adenovirus
      (Ad) DNA replication and forms a heterodimer with Ad DNA polymerase (pol). Pol
      can couple dCTP to pTP directed by the fourth nucleotide of the viral genome
      template strand in the absence of other replication proteins, which suggests that
      pTP/pol binding destabilizes the origin or stabilizes an unwound state. We
      analyzed the contribution of pTP to pTP/pol origin binding using various DNA
      oligonucleotides. We show that two pTP molecules bind cooperatively to short DNA
      duplexes, while longer DNA fragments are bound by single pTP molecules as well.
      Cooperative binding to short duplexes is DNA sequence independent and most likely
      mediated by protein/protein contacts. Furthermore, we observed that pTP binds
      single-stranded (ss)DNA with a minimal length of approximately 35 nt and that
      random ssDNA competed 25-fold more efficiently than random duplex DNA for origin
      binding by pTP. Remarkably, short DNA fragments with two opposing single strands
      supported monomeric pTP binding. pTP did not stimulate, but inhibited strand
      displacement by the Ad DNA binding and unwinding protein DBP. These observations
      suggest a mechanism in which the ssDNA affinity of pTP stabilizes Ad pol on
      partially unwound origin DNA.

PMID- 12799456
TI  - Optimization of high-density cDNA-microarray protocols by 'design of
      experiments'.
AB  - Expression analysis using microarray technology implies a complex experimental
      procedure with a large number of parameters affecting the final result. We have
      demonstrated that optimization of such a complex protocol can be far better
      handled using design of experiments (DOE) than by working on a single parameter
      at a time. Based on the results of a screening design, we developed a spotting
      buffer composed of formamide, betaine and nitrocellulose. This buffer provides a
      2-fold increase in signal-to-background ratio compared to 3x SSC. Comparison to
      seven other buffers tested on 10 different substrates revealed it had the highest
      sensitivity. DNA dissolved in this buffer can be spotted on epoxysilane-coated
      microscope slides at a density of up to 70 000 spots per slide. A second DOE
      approach characterized the RNA labeling process with regard to the concentration
      of fluorescent dyes, dNTPs and reverse transcriptase. Adjust ments of the
      concentrations of dNTPs, as well as reverse transcriptase, towards the optimum,
      produced an improvement in the performance of the labeling procedure by a factor
      of 3 (Cy3) and 10 (Cy5). These results demonstrate that the process of
      establishing a stable expression profiling protocol and its further optimization
      can be significantly shortened and improved by DOE.

PMID- 12799457
TI  - T-linker-specific ligation PCR (T-linker PCR): an advanced PCR technique for
      chromosome walking or for isolation of tagged DNA ends.
AB  - Dozens of PCR-based methods are available for chromosome walking from a known
      sequence to an unknown region. These methods are of three types: inverse PCR,
      ligation-mediated PCR and randomly primed PCR. However, none of them has been
      generally applied for this purpose, because they are either difficult or
      inefficient. Here we describe a simple and efficient PCR strategy--T-linker
      specific ligation PCR (T-linker PCR) for gene or chromosome walking. The strategy
      amplifies the template molecules in three steps. First, genomic DNA is digested
      with 3' overhang enzymes. Secondly, primed by a specific primer, a strand of the
      target molecule is replicated by Taq DNA polymerase and a single A tail is
      generated on the 3' unknown end of the target molecule, and then a 3' overhang-T
      linker (named T-linker) is specifically ligated onto the target. Thirdly, the
      target is amplified by two rounds of nested PCR with specific primers and T
      linker primers. T-linker PCR significantly improves the existing PCR methods for
      walking because it uses specific T/A ligation instead of arbitrary ligation or
      random annealing. To show the feasibility and efficiency of T-linker PCR, we have
      exploited this method to identify vector DNA or T-DNA insertions in transgenic
      plants.

PMID- 12799459
TI  - Human pancreatic precursor cells secrete FGF2 to stimulate clustering into
      hormone-expressing islet-like cell aggregates.
AB  - Development of the endocrine pancreas includes a series of early events wherein
      precursor cells cluster, that is migrate to form cell aggregates, which
      subsequently differentiate into islets of Langerhans. We show that PANC-1 cells,
      a human pancreatic cell line, differentiates into hormone-producing islet-like
      cell aggregates after exposure to a defined serum-free medium. These cells were
      used to provide the following evidence that fibroblast growth factor (FGF)2 is a
      paracrine chemoattractant during PANC-1 cell clustering: (i) FGF2 is secreted and
      remains bound to the extracellular matrix from where it may diffuse to form
      chemoattractive gradients; (ii) a subset of cells expresses FGF receptors (FGFRs)
      -1, -2, -3, and -4; (iii) inhibition of FGFR tyrosine kinase inhibits cell
      clustering; and (iv) FGF2 neutralizing antibody inhibits clustering. In addition,
      adult human islet-derived precursor cells, which cluster and differentiate in a
      manner similar to PANC-1 cells, also secrete FGF2 and express FGFRs. We conclude
      that FGF2, acting as a paracrine chemoattractant, stimulates clustering of
      precursor cells, an early step leading to islet-like cell aggregate formation.
      Similar processes may occur during development of the islet of Langerhans in
      humans.

PMID- 12799458
TI  - Conditional human VEGF-mediated vascularization in chicken embryos using a novel
      temperature-inducible gene regulation (TIGR) system.
AB  - Advanced heterologous transcription control systems for adjusting desired
      transgene expression are essential for gene function assignments, drug discovery,
      manufacturing of difficult to produce protein pharmaceuticals and precise dosing
      of gene-based therapeutic interventions. Conversion of the Streptomyces albus
      heat shock response regulator (RheA) into an artificial eukaryotic transcription
      factor resulted in a vertebrate thermosensor (CTA; cold-inducible
      transactivator), which is able to adjust transcription initiation from chimeric
      target promoters (P(CTA)) in a low-temperature- inducible manner. Evaluation of
      the temperature-dependent CTA-P(CTA) interaction using a tailored ELISA-like cell
      free assay correlated increased affinity of CTA for P(CTA) with temperature
      downshift. The temperature-inducible gene regulation (TIGR) system enabled tight
      repression in the chicken bursal B-cell line DT40 at 41 degrees C as well as
      precise titration of model product proteins up to maximum expression at or below
      37 degrees C. Implantation of microencapsulated DT40 cells engineered for TIGR
      controlled expression of the human vascular endothelial growth factor A
      (hVEGF121) provided low-temperature-induced VEGF-mediated vascularization in
      chicken embryos.

PMID- 12799460
TI  - Function and glycosylation of plant-derived antiviral monoclonal antibody.
AB  - Plant genetic engineering led to the production of plant-derived mAb (mAbP),
      which provides a safe and economically feasible alternative to the current
      methods of antibody production in animal systems. In this study, the heavy and
      light chains of human anti-rabies mAb were expressed and assembled in planta
      under the control of two strong constitutive promoters. An alfalfa mosaic virus
      untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum
      retention signal were linked at the N and C terminus of the heavy chain,
      respectively. mAbP was as effective at neutralizing the activity of the rabies
      virus as the mammalian-derived antibody (mAbM) or human rabies Ig (HRIG). The
      mAbP contained mainly oligomannose type N-glycans (90%) and had no potentially
      antigenic alpha(1,3)-linked fucose residues. mAbP had a shorter half-life than
      mAbM. The mAbP was as efficient as HRIG for post-exposure prophylaxis against
      rabies virus in hamsters, indicating that differences in N-glycosylation do not
      affect the efficacy of the antibody in this model.

PMID- 12799461
TI  - High-resolution structure of RNase P protein from Thermotoga maritima.
AB  - The structure of RNase P protein from the hyperthermophilic bacterium Thermotoga
      maritima was determined at 1.2-A resolution by using x-ray crystallography. This
      protein structure is from an ancestral-type RNase P and bears remarkable
      similarity to the recently determined structures of RNase P proteins from
      bacteria that have the distinct, Bacillus type of RNase P. These two types of
      protein span the extent of bacterial RNase P diversity, so the results generalize
      the structure of the bacterial RNase P protein. The broad phylogenetic
      conservation of structure and distribution of potential RNA-binding elements in
      the RNase P proteins indicate that all of these homologous proteins bind to their
      cognate RNAs primarily by interaction with the phylogenetically conserved core of
      the RNA. The protein is found to dimerize through an extensive, well-ordered
      interface. This dimerization may reflect a mechanism of thermal stability of the
      protein before assembly with the RNA moiety of the holoenzyme.

PMID- 12799462
TI  - A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits
      IL-1 receptor-mediated responses.
AB  - Toll-like receptors (TLRs) and the type I IL-1 receptor (IL-1RI) are key
      components of the innate immune system activated by microbial infections and
      inflammation. The signaling cascade from agonist-occupied TLRs and IL-1Rs
      involves recruitment of the small cytosolic adapter protein MyD88 that binds to
      IL-1RI via homotypic interactions mediated by Toll/IL-1R/resistance (TIR)
      domains. Dominant negative forms and null mutations of MyD88 have recently been
      shown to preclude bacterial product or IL-1-mediated activation of NF-kappaB
      pathways, demonstrating that MyD88 is an essential component of the Toll receptor
      signaling. Here, we report the synthesis and pharmacological effects of a low
      molecular weight MyD88 mimic, hydrocinnamoyl-l-valyl pyrrolidine (compound 4a),
      modeled on a tripeptide sequence of the BB-loop [(F/Y)-(V/L/I)-(P/G)] of the TIR
      domain. Results are presented showing that compound 4a interferes with the
      interactions between mouse MyD88 and IL-1RI at the TIR domains. Compound 4a
      inhibited IL-1beta-induced phosphorylation of the mitogen-activated protein
      kinase p38 in EL4 thymoma cells and in freshly isolated murine lymphocytes in a
      concentration-dependent manner. In vivo, compound 4a produced a significant
      attenuation of the IL-1beta-induced fever response (200 mg/kg, i.p.). Inhibition
      of the TIR domain-mediated MyD88/IL1-RI interaction by a low molecular weight,
      cell-penetrating TIR domain mimic suggests an intracellular site for
      antiinflammatory drug action.

PMID- 12799463
TI  - Comparative sequencing of human and chimpanzee MHC class I regions unveils
      insertions/deletions as the major path to genomic divergence.
AB  - Despite their high degree of genomic similarity, reminiscent of their relatively
      recent separation from each other ( approximately 6 million years ago), the
      molecular basis of traits unique to humans vs. their closest relative, the
      chimpanzee, is largely unknown. This report describes a large-scale single-contig
      comparison between human and chimpanzee genomes via the sequence analysis of
      almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of
      DNA, which encompasses the entire class I along with the telomeric part of the
      MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human
      HLA region. Sequence analysis confirms the existence of a high degree of sequence
      similarity between the two species. However, and importantly, this 98.6% sequence
      identity drops to only 86.7% taking into account the multiple
      insertions/deletions (indels) dispersed throughout the region. This is
      functionally exemplified by a large deletion of 95 kb between the virtual
      locations of human MICA and MICB genes, which results in a single hybrid
      chimpanzee MIC gene, in a segment of the MHC genetically linked to species
      specific handling of several viral infections (HIV/SIV, hepatitis B and C) as
      well as susceptibility to various autoimmune diseases. Finally, if generalized,
      these data suggest that evolution may have used the mechanistically more drastic
      indels instead of the more subtle single-nucleotide substitutions for shaping the
      recently emerged primate species.

PMID- 12799464
TI  - Prostate intraepithelial neoplasia induced by prostate restricted Akt activation:
      the MPAKT model.
AB  - To determine whether Akt activation was sufficient for the transformation of
      normal prostate epithelial cells, murine prostate restricted Akt kinase activity
      was generated in transgenic mice (MPAKT mice). Akt expression led to p70S6K
      activation, prostatic intraepithelial neoplasia (PIN), and bladder obstruction.
      mRNA expression profiles from MPAKT ventral prostate revealed similarities to
      human cancer and an angiogenic signature that included three angiogenin family
      members, one of which was found elevated in the plasma of men with prostate
      cancer. Thus, the MPAKT model may be useful in studying the role of Akt in
      prostate epithelial cell transformation and in the discovery of molecular markers
      relevant to human disease.

PMID- 12799465
TI  - A newly discovered cholesteryl galactoside from Borrelia burgdorferi.
AB  - Two major glycolipids, which comprise approximately 36% of the total lipid mass
      from Borrelia burgdorferi, the etiological agent of Lyme disease, were
      investigated. We determined the fatty acid type, sugar identity, anomeric
      configuration, and substituent type and position. The structures were identified
      as cholesteryl 6-O-acyl-beta-d-galactopyranoside (B. burgdorferi glycolipid 1,
      BbGL-I), and 1,2-di-O-acyl-3-O-alpha-d-galactopyranosyl-sn-glycerol (BbGL-II).
      The major fatty acids were palmitate and oleate. The structures were corroborated
      by gas-liquid chromatography MS, matrix-assisted laser desorption/ionization time
      of-flight spectroscopy, fast atom bombardment MS, detailed NMR spectrometry, and
      metabolic labeling. This is a previously undescribed demonstration of a
      cholesteryl galactoside in bacteria. Lipopolysaccharide was not detected in B.
      burgdorferi. The two glycolipids have several properties suggesting they may
      function as lipopolysaccharide: both are main components of the bacterial
      membrane, surface exposed, and have a three-domain structure. BbGL-I elicited
      specific antibodies in mice and rabbits, and BbGL-II elicited antibodies that
      reacted with both glycolipids.

PMID- 12799467
TI  - Suppressed catalytic activity of base excision repair enzymes on rotationally
      positioned uracil in nucleosomes.
AB  - The majority of DNA in eukaryotic cells exists in the highly condensed structural
      hierarchy of chromatin, which presents a challenge to DNA repair enzymes in that
      recognition, incision, and restoration of the original sequence at most sites
      must take place within these structural constraints. To test base excision repair
      (BER) activities on chromatin substrates, an in vitro system was developed that
      uses human uracil DNA glycosylase (UDG), apyrimidinic/apurinic endonuclease
      (APE), and DNA polymerase beta (pol beta) on homogeneously damaged, rotationally
      positioned DNA in nucleosomes. We find that UDG and APE carry out their combined
      catalytic activities with reduced efficiency on nucleosome substrates (
      approximately 10% of that on naked DNA). Furthermore, these enzymes distinguish
      between two different rotational settings of the lesion on the histone surface,
      showing a 2- to 3-fold difference in activity between uracil facing "toward" and
      "away from" the histones. However, UDG and APE will digest such substrates to
      completion in a concentration-dependent manner. Conversely, the synthesis
      activity of pol beta is inhibited completely by nucleosome substrates and is
      independent of enzyme concentration. These results suggest that the first two
      steps of BER, UDG and APE, may occur "unassisted" in chromatin, whereas
      downstream factors in this pathway (i.e., pol beta) may require nucleosome
      remodeling for efficient DNA BER in at least some regions of chromatin in
      eukaryotic cells.

PMID- 12799468
TI  - Developing an energy landscape for the novel function of a (beta/alpha)8 barrel:
      ammonia conduction through HisF.
AB  - HisH-hisF is a multidomain globular protein complex; hisH is a class I glutamine
      amidotransferase that hydrolyzes glutamine to form ammonia, and hisF is a
      (beta/alpha)8 barrel cyclase that completes the ring formation of imidizole
      glycerol phosphate synthase. Together, hisH and hisF form a glutamine
      amidotransferase that carries out the fifth step of the histidine biosynthetic
      pathway. Recently, it has been suggested that the (beta/alpha)8 barrel
      participates in a novel function: to channel ammonia from the active site of hisH
      to the active site of hisF. The present study presents a series of molecular
      dynamic simulations that investigate the channeling function of hisF. This
      article reconstructs potentials of mean force for the conduction of ammonia
      through the channel, and the entrance of ammonia through the strictly conserved
      channel gate, in both a closed and a hypothetical open conformation. The
      resulting energy landscape within the channel supports the idea that ammonia does
      indeed pass through the barrel, interacting with conserved hydrophilic residues
      along the way. The proposed open conformation, which involves an alternate
      rotamer state of one of the gate residues, presents only an approximately 2.5
      kcal energy barrier to ammonia entry. Another alternate open-gate conformation,
      which may play a role in non-nitrogen-fixing organisms, is deduced through
      bioinformatics.

PMID- 12799466
TI  - Single-nucleotide polymorphisms and genome diversity in Plasmodium vivax.
AB  - The study of genetic variation in malaria parasites has practical significance
      for developing strategies to control the disease. Vaccines based on highly
      polymorphic antigens may be confounded by allelic restriction of the host immune
      response. In response to drug pressure, a highly plastic genome may generate
      resistant mutants more easily than a monomorphic one. Additionally, the study of
      the distribution of genomic polymorphisms may provide information leading to the
      identification of genes associated with traits such as parasite development and
      drug resistance. Indeed, the age and diversity of the human malaria parasite
      Plasmodium falciparum has been the subject of recent debate, because an ancient
      parasite with a complex genome is expected to present greater challenges for drug
      and vaccine development. The genome diversity of the important human pathogen
      Plasmodium vivax, however, remains essentially unknown. Here we analyze an
      approximately 100-kb contiguous chromosome segment from five isolates, revealing
      191 single-nucleotide polymorphisms (SNPs) and 44 size polymorphisms. The SNPs
      are not evenly distributed across the segment with blocks of high and low
      diversity. Whereas the majority (approximately 63%) of the SNPs are in intergenic
      regions, introns contain significantly less SNPs than intergenic sequences.
      Polymorphic tandem repeats are abundant and are more uniformly distributed at a
      frequency of about one polymorphic tandem repeat per 3 kb. These data show that
      P. vivax has a highly diverse genome, and provide useful information for further
      understanding the genome diversity of the parasite.

PMID- 12799469
TI  - Control of in vitro organogenesis by cyclin-dependent kinase activities in
      plants.
AB  - Little is known concerning the mechanisms by which auxin and cytokinin exert
      their effects on proliferation and differentiation. Cyclin-dependent kinases
      (CDKs) are major regulators of the eukaryotic cell cycle, thus they are assumed
      to control cell differentiation as well as proliferation in response to
      phytohormone signals. Here, we overexpressed rice R2 cDNA, which encodes a CDK
      activating kinase, in tobacco leaf explants by using the glucocorticoid-mediated
      transcriptional induction system. Transient expression of R2 during the first 7
      days of culture triggered callus formation in the absence of cytokinin. This
      phenotype was enhanced by higher expression of R2 or coexpression of cyclin H,
      and suppressed by treatment with roscovitine, a CDK inhibitor. R2 expression at a
      later stage did not prevent cells from differentiation into roots, suggesting a
      restricted period for sensing CDK activities that control differentiation fate of
      cells during organogenesis.

PMID- 12799471
TI  - Early onset albuminuria in Dahl rats is a polygenetic trait that is independent
      from salt loading.
AB  - The aim of the study was to characterize the genetic basis for the early onset of
      increased urinary albumin excretion (UAE) observed in the salt-sensitive Dahl rat
      (SS). We first characterized blood pressures and UAE values in adult SS compared
      with the spontaneously hypertensive rat (SHR) strain. Blood pressure measurements
      by radiotelemetry at 14 wk demonstrated similar spontaneous hypertension in both
      strains on a low-sodium diet containing 0.2% NaCl by weight, whereas UAE was
      markedly increased in SS compared with SHR (253.07 +/- 68.39 vs. 1.65 +/- 1.09
      mg/24 h, P < 0.0001). Analysis of UAE in young animals of both strains fed a low
      sodium diet demonstrated that UAE is elevated in SS as early as 4 wk of age (P <
      0.0001), when ultrastructural evaluation of glomeruli by electron microscopy
      appears still normal. At 8 wk SS demonstrated a 280-fold elevated UAE compared
      with SHR (P < 0.0001). Consequently, to identify quantitative trait loci (QTLs)
      contributing to salt-independent early manifestation of increased UAE in the SS
      rat, we performed genome-wide linkage and QTL mapping analysis in a young F(2)
      population derived from the two contrasting strains. UAE was determined in 539
      F(2) animals at 8 wk. We identified seven suggestive or significant UAE QTLs on
      rat chromosomes (RNO) RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, and RNO19, accounting
      together for 34% of the overall variance of UAE in this F(2) population. Thus
      early onset albuminuria in the SS rat is under polygenetic influence and
      independent from salt loading.

PMID- 12799470
TI  - Systematic discovery of multicomponent therapeutics.
AB  - Multicomponent therapies, originating through deliberate mixing of drugs in a
      clinical setting, through happenstance, and through rational design, have a
      successful history in a number of areas of medicine, including cancer, infectious
      diseases, and CNS disorders. We have developed a high-throughput screening method
      for identifying effective combinations of therapeutic compounds. We report here
      that systematic screening of combinations of small molecules reveals unexpected
      interactions between compounds, presumably due to interactions between the
      pathways on which they act. Through systematic screening of approximately 120,000
      different two-component combinations of reference-listed drugs, we identified
      potential multicomponent therapeutics, including (i) fungistatic and analgesic
      agents that together generate fungicidal activity in drug-resistant Candida
      albicans, yet do not significantly affect human cells, (ii) glucocorticoid and
      antiplatelet agents that together suppress the production of tumor necrosis
      factor-alpha in human primary peripheral blood mononu-clear cells, and (iii)
      antipsychotic and antiprotozoal agents that do not exhibit significant antitumor
      activity alone, yet together prevent the growth of tumors in mice. Systematic
      combination screening may ultimately be useful for exploring the connectivity of
      biological pathways and, when performed with reference-listed drugs, may result
      in the discovery of new combination drug regimens.

PMID- 12799472
TI  - Transcriptional profiling and regulation of the extracellular matrix during
      muscle regeneration.
AB  - Muscle regeneration is a complex process requiring the coordinated interaction
      between the myogenic progenitor cells or satellite cells, growth factors,
      cytokines, inflammatory components, vascular components and the extracellular
      matrix (ECM). Previous studies have elegantly described the physiological
      modulation of the regenerative process in response to muscle injury, but the
      molecular response that characterizes stages of the repair process remains ill
      defined. The recent completion of the Human and Mouse Genome Projects and the
      advent of technologies such as high-density oligonucleotide array analysis
      facilitate an expanded analysis of complex processes such as muscle regeneration.
      In the present study, we define cellular and molecular events that characterize
      stages of muscle injury and regeneration. Utilization of transcriptional
      profiling strategies revealed coordinated expression of growth factors [i.e.,
      Tgfb1, Igf1, Egf, chemokine (C-C motif) ligand 6 and 7], the fetal myogenic
      program (Myod1, Myf5, Myf6), and the biomatrix (procollagen genes, Mmp3, Mmp9,
      biglycan, periostin) during muscle regeneration. Corroboration of the
      transcriptional profiling analysis included quantitative real-time RT-PCR and in
      situ hybridization analyses of selected candidate genes. In situ hybridization
      studies for periostin [osteoblast-specific factor 2 (fasciclin I-like)] and
      biglycan revealed that these genes are restricted to mesenchymal derivatives
      during embryogenesis and are significantly regulated during regeneration of the
      injured hindlimb skeletal muscle. We conclude that muscle regeneration is a
      complex process that requires the coordinated modulation of the inflammatory
      response, myogenic progenitor cells, growth factors, and ECM for complete
      restoration of muscle architecture.

PMID- 12799473
TI  - Quantitative assessment of the importance of dye switching and biological
      replication in cDNA microarray studies.
AB  - Dye switching and biological replication substantially increase the cost and the
      complexity of cDNA microarray studies. The objective of the present analysis was
      to quantitatively assess the importance of these procedures to provide a
      quantitative basis for decision-making in the design of microarray experiments.
      Taking advantage of the unique characteristics of a published data set, the
      impact of these procedures on the reliability of microarray results was
      calculated. Adding a second microarray with dye switching substantially increased
      the correlation coefficient between observed and predicted ln(ratio) values from
      0.38 +/- 0.06 to 0.62 +/- 0.04 (n = 12) and the outlier concordance from 21 +/-
      3% to 43 +/- 4%. It also increased the correlation with the entire set of
      microarrays from 0.60 +/- 0.04 to 0.79 +/- 0.04 and the outlier concordance from
      31 +/- 6% to 58 +/- 5% and tended to improve the correlation with Northern blot
      results. Adding a second microarray to include biological replication also
      improved the performance of these indices but often to a lesser degree. Inclusion
      of both procedures in the second microarray substantially improved the
      consistency with the entire set of microarrays but had minimal effect on the
      consistency with predicted results. Analysis of another data set generated using
      a different cDNA labeling method also supported a significant impact of dye
      switching. In conclusion, both dye switching and biological replication
      substantially increased the reliability of microarray results, with dye switching
      likely having even greater benefits. Recommendations regarding the use of these
      procedures were proposed.

PMID- 12799475
TI  - The challenge of hepatitis C surveillance in Europe.

PMID- 12799476
TI  - Surveillance of screening for hepatitis C through the laboratory network RENA
      VHC, France, 2000-2001.
AB  - Over the period 2000-2001, 189 private or hospital laboratories scattered
      throughout France participated to the laboratory network RENA-VHC. A total of 759
      591 serologies (screening tests and validation of screening tests) were
      performed, revealing an increase of 10% between 2000 and 2001. The rate of the
      amount of tests to validate screening found positive over the overall amount of
      tests performed was 1.2% in 2000 and 1.0% in 2001. This suggests that screening
      covered more people with little risk of acquiring HCV infection. The per-sons
      confirmed HCV positive were predominantly men (sex ratio 1.5) of which 31% were
      30 to 39 years of age.

PMID- 12799477
TI  - Surveillance of HCV infection in the Netherlands.
AB  - Two surveillance systems exist in the Netherlands to monitor hepatitis C (HCV)
      infections. Aggregated weekly laboratory data have been available since 1990. In
      1999, HCV infection became a notifiable disease. Data showed the number of
      reported cases has remained stable. Male cases predominated (66%), mainly between
      age 15 to 54. Injecting drug use was the main route of transmission (64%).
      Despite its added value, the notifiable system should include more clinical data
      to better scrutinize future changes in transmission patterns.

PMID- 12799478
TI  - Hepatitis C in Austria 1993-2000: reporting bias distort HCV epidemiology in
      Austria.
AB  - From 1993 to 2000 in Austria, the notification system registered 2232 cases of
      hepatitis C whereas 10 607 hospital cases were reported in the hospital discharge
      register (HDR). These differences can be explained by under-reporting due to lax
      reporting behaviour and stigma associated with this disease. The distribution of
      HCV infection varied geographically. The notification data showed the highest
      incidence rates in Tyrol, while HDR data showed highest hospitalisation rates in
      Vienna and Lower Austria. This study highlights the urgent need for a clear case
      definition at the national level and an electronic reporting system.

PMID- 12799479
TI  - Severe acute respiratory syndrome (SARS).

PMID- 12799480
TI  - Severe acute respiratory syndrome (SARS): an old virus jumping into a new host or
      a new creation?

PMID- 12799481
TI  - Blueprint of a red mould: Unusual and unexpected findings in the Neurospora
      genome sequence.

PMID- 12799482
TI  - A branched chain fatty acid promotes cold adaptation in bacteria.

PMID- 12799484
TI  - Can we obtain realistic HIV/AIDS estimates for India?

PMID- 12799483
TI  - HIV necessary though not sufficient for AIDS.

PMID- 12799485
TI  - Origin of the neutral and nearly neutral theories of evolution.

PMID- 12799486
TI  - Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced
      test sensitivity.
AB  - Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific
      method for the analysis of adenosine-5-triphosphate (ATP) in biological samples.
      Earlier attempts to modify the FLB test for enhanced sensitivity have been
      typically based on in vitro cell systems. This study reports an optimized FLB
      procedure for the analysis of ATP in small tissue samples. The results showed
      that the sensitivity of the FLB test can be enhanced several fold by using
      ultraturax homogenizer, perchloric acid extraction, neutralization of acid
      extract and its optimal dilution, before performing the assay reaction.

PMID- 12799488
TI  - Regulation of activity of the yeast TATA-binding protein through intra-molecular
      interactions.
AB  - Dimerization is proposed to be a regulatory mechanism for TATA-binding protein
      (TBP) activity both in vitro and in vivo. The reversible dimer-monomer transition
      of TBP is influenced by the buffer conditions in vitro. Using in vitro chemical
      cross-linking, we found yeast TBP (yTBP) to be largely monomeric in the presence
      of the divalent cation Mg2+, even at high salt concentrations. Apparent molecular
      mass of yTBP at high salt with Mg2+, run through a gel filtration column, was
      close to that of monomeric yTBP. Lowering the monovalent ionic concentration in
      the absence of Mg2+, resulted in dimerization of TBP. Effect of Mg2+ was seen at
      two different levels: at higher TBP concentrations, it suppressed the TBP
      dimerization and at lower TBP levels, it helped keep TBP monomers in active
      conformation (competent for binding TATA box), resulting in enhanced TBP-TATA
      complex formation in the presence of increasing Mg2+. At both the levels,
      activity of the full-length TBP in the presence of Mg2+ was like that reported
      for the truncated C-terminal domain of TBP from which the N-terminus is removed.
      Therefore for full-length TBP, intra-molecular interactions can regulate its
      activity via a similar mechanism.

PMID- 12799490
TI  - Hypervariable spacer regions are good sites for developing specific PCR-RFLP
      markers and PCR primers for screening actinorhizal symbionts.
AB  - While the ribosomal RNA like highly conserved genes are good molecular
      chronometers for establishing phylogenetic relationships, they can also be useful
      in securing the amplification of adjoining hyper-variable regions. These regions
      can then be used for developing specific PCR primers or PCR-RFL profiles to be
      used as molecular markers. We report here the use of ITS region of rrn operon of
      Frankia for developing PCR-RFL profiles capable of discriminating between closely
      related frankiae. We have also made use of the ITS1 region of the nuclear rrn
      operon of Alnus nepalensis (D Don) for designing a PCR primer for specific
      amplification of nuclear DNA of this tree.

PMID- 12799489
TI  - The transcriptional activator GAL4-VP16 regulates the intra-molecular
      interactions of the TATA-binding protein.
AB  - Binding characteristics of yeast TATA-binding protein (yTBP) over five oligomers
      having different TATA variants and lacking a UASGAL, showed that TATA-binding
      protein (TBP)-TATA complex gets stabilized in the presence of the acidic
      activator GAL4-VP16. Activator also greatly suppressed the non-specific TBP-DNA
      complex formation. The effects were more pronounced over weaker TATA boxes.
      Activator also reduced the TBP dimer levels both in vitro and in vivo, suggesting
      the dimer may be a direct target of transcriptional activators. The
      transcriptional activator facilitated the dimer to monomer transition and
      activated monomers further to help TBP bind even the weaker TATA boxes stably.
      The overall stimulatory effect of the GAL4-VP16 on the TBP-TATA complex formation
      resembles the known effects of removal of the N-terminus of TBP on its activity,
      suggesting that the activator directly targets the N-terminus of TBP and
      facilitates its binding to the TATA box.

PMID- 12799487
TI  - The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral
      chemotherapy and malnutrition.
AB  - In 1981 a new epidemic of about two-dozen heterogeneous diseases began to strike
      non-randomly growing numbers of male homosexuals and mostly male intravenous drug
      users in the US and Europe. Assuming immunodeficiency as the common denominator
      the US Centers for Disease Control (CDC) termed the epidemic, AIDS, for acquired
      immunodeficiency syndrome. From 1981-1984 leading researchers including those
      from the CDC proposed that recreational drug use was the cause of AIDS, because
      of exact correlations and of drug-specific diseases. However, in 1984 US
      government researchers proposed that a virus, now termed human immunodeficiency
      virus (HIV), is the cause of the non-random epidemics of the US and Europe but
      also of a new, sexually random epidemic in Africa. The virus-AIDS hypothesis was
      instantly accepted, but it is burdened with numerous paradoxes, none of which
      could be resolved by 2003: Why is there no HIV in most AIDS patients, only
      antibodies against it? Why would HIV take 10 years from infection to AIDS? Why is
      AIDS not self-limiting via antiviral immunity? Why is there no vaccine against
      AIDS? Why is AIDS in the US and Europe not random like other viral epidemics? Why
      did AIDS not rise and then decline exponentially owing to antiviral immunity like
      all other viral epidemics? Why is AIDS not contagious? Why would only HIV
      carriers get AIDS who use either recreational or anti-HIV drugs or are subject to
      malnutrition? Why is the mortality of HIV-antibody-positives treated with anti
      HIV drugs 7-9%, but that of all (mostly untreated) HIV-positives globally is only
      1.4%? Here we propose that AIDS is a collection of chemical epidemics, caused by
      recreational drugs, anti-HIV drugs, and malnutrition. According to this
      hypothesis AIDS is not contagious, not immunogenic, not treatable by vaccines or
      antiviral drugs, and HIV is just a passenger virus. The hypothesis explains why
      AIDS epidemics strike non-randomly if caused by drugs and randomly if caused by
      malnutrition, why they manifest in drug- and malnutrition-specific diseases, and
      why they are not self-limiting via anti-viral immunity. The hypothesis predicts
      AIDS prevention by adequate nutrition and abstaining from drugs, and even cures
      by treating AIDS diseases with proven medications.

PMID- 12799492
TI  - Structural and histochemical studies on grain-filling in the caryopsis of rice
      (Oryza sativa L.).
AB  - The endosperm and embryo that constitute the filial tissues of rice caryopsis are
      isolated from the maternal tissues by the absence of any symplastic continuity.
      Nutrients are transported to the endosperm through a single ovular vascular trace
      present on the ventral side of the ovary. Initially solute enters through the
      chalaza into the nucellar projection and then into the endosperm. At later stages
      transport occurs through the nucellar epidermis, centripetally towards the
      endosperm. The cell walls of the nucellar epidermis are provided with rib-like
      thicken ings. A comparison of grain-filling in C3 and C4 cereals suggests that
      rice has structural features allied to C3 cereals, such as wheat, but with
      significant differences.

PMID- 12799491
TI  - A comparative phylogenetic analysis of full-length mariner elements isolated from
      the Indian tasar silkmoth, Antheraea mylitta (Lepidoptera: saturniidae).
AB  - Mariner like elements (MLEs) are widely distributed type II transposons with an
      open reading frame (ORF) for transposase. We studied comparative phylogenetic
      evolution and inverted terminal repeat (ITR) conservation of MLEs from Indian
      saturniid silkmoth, Antheraea mylitta with other full length MLEs submitted in
      the database. Full length elements from A. mylitta were inactive with multiple
      mutations. Many conserved amino acid blocks were identified after aligning
      transposase sequences. Mariner signature sequence, DD(34)D was almost inva ri
      able although a few new class of elements had different signatures. A. mylitta
      MLEs (Anmmar) get phylogene ti cally classified under cecropia subfamily and
      cluster closely with the elements from other Bombycoidea superfamily members
      implying vertical transmission from a common ancestor. ITR analysis showed a
      conserved sequence of AGGT(2-8N)ATAAGT for forward repeat and AGGT(2-8N)ATGAAAT
      for reverse repeat. These results and additional work may help us to understand
      the dynamics of MLE distribution in A. mylitta and construction of appropriate
      vectors for mariner mediated transgenics.

PMID- 12799493
TI  - Subcellular localization of Cd in the root cells of Allium sativum by electron
      energy loss spectroscopy.
AB  - The ultrastructural investigation of the root cells of Allium sativum L. exposed
      to three different concentrations of Cd (100 mM, 1 mM and 10 mM) for 9 days was
      carried out. The results showed that Cd induced several significant
      ultrastructural changes   high vacuolization in cytoplasm, deposition of electron
      dense material in vacuoles and nucleoli and increment of disintegrated
      organelles. Data from electron energy loss spectroscopy (EELS) revealed that Cd
      was localized in the electron-dense precipitates in the root cells treated with
      10 mM Cd. High amounts of Cd were mainly accumulated in the vacuoles and nucleoli
      of cortical cells in differentiating and mature root tissues. The mechanisms of
      detoxification and tolerance of Cd are briefly explained.

PMID- 12799494
TI  - Sucrose mobilization in relation to essential oil biogenesis during palmarosa
      (Cymbopogon martinii Roxb. Wats. var. motia) inflorescence development.
AB  - Palmarosa inflorescence with partially opened spikelets is biogenetically active
      to incorporate [U-14C]sucrose into essential oil. The percent distribution of 14C
      radioactivity incorporated into geranyl acetate was relatively higher as compared
      to that in geraniol, the major essential oil constituent of palmarosa. At the
      partially opened spikelet stage, more of the geraniol synthesized was acetylated
      to form geranyl acetate, suggesting that majority of the newly synthesized
      geraniol undergoes acetylation, thus producing more geranyl acetate. In vitro
      development of palmarosa inflorescence, fed with [U-14C]sucrose, resulted in a
      substantial reduction in percent label from geranyl acetate with a corresponding
      increase in free geraniol, thereby suggesting the role of an esterase in the
      production of geraniol from geranyl acetate. At time course measurement of 14CO2
      incorporation into geraniol and geranyl acetate substantiated this observation.
      Soluble acid invertase was the major enzyme involved in the sucrose breakdown
      throughout the inflorescence development. The activities of cell wall bound acid
      invertase, alkaline invertase and sucrose synthase were relatively lower as
      compared to the soluble acid invertase. Sucrose to reducing sugars ratio
      decreased till fully opened spikelets stage, concomitant with increased acid
      invertase activity and higher metabolic activity. The phenomenon of essential oil
      biosynthesis has been discussed in relation to changes in these physiological
      parameters.

PMID- 12799495
TI  - Density-dependent growth and metamorphosis in the larval bronze frog Rana
      temporalis is influenced by genetic relatedness of the cohort.
AB  - Effects of density and kinship on growth and metamorphosis in tadpoles of Rana
      temporalis were studied in a 2   4 factorial experiment. Fifteen egg masses were
      collected from streams in the Western Ghat region of south India. The tadpoles
      were raised as siblings or in groups of non-siblings at increasing density
      levels, viz. 15, 30, 60 and 120/5 l water. With an increase in density level from
      15 to 120 tadpoles/5 l water, duration of the larval stage increased and fewer
      individuals metamorphosed irrespective of whether they belonged to sibling or non
      sibling groups by day 100 when the experiments were terminated. The size of
      individuals at metamorphosis declined significantly with increase in the density
      of rearing. However, at higher densities (60 and 120 tadpoles/5 l water) sibling
      group tadpoles performed better compared to mixed groups and took significantly
      less time to metamorphose. Also, more individuals of sibling groups metamorphosed
      compared to non-sibling groups at a given density. Mixed rearing retarded growth
      rates, prolonged larval duration resulting in a wider spectrum of size classes,
      and lowered the number of individuals recruited to terrestrial life. The study
      shows that interference competition occurred more strongly in cohorts of mixed
      relatedness than in sibling groups.

PMID- 12799496
TI  - A technique for estimating maximum harvesting effort in a stochastic fishery
      model.
AB  - Exploitation of biological resources and the harvest of population species are
      commonly practiced in fisheries, forestry and wild life management. Estimation of
      maximum harvesting effort has a great impact on the economics of fisheries and
      other bio-resources. The present paper deals with the problem of a bioeconomic
      fishery model under environmental variability. A technique for finding the
      maximum harvesting effort in fluctuating environment has been developed in a two
      species competitive system, which shows that under realistic environmental
      variability the maximum harvesting effort is less than what is estimated in the
      deterministic model. This method also enables us to find out the safe regions in
      the parametric space for which the chance of extinction of the species is
      minimized. A real life fishery problem has been considered to obtain the
      inaccessible parameters of the system in a systematic way. Such studies may help
      resource managers to get an idea for controlling the system.

PMID- 12799497
TI  - Status of Austro-Asiatic groups in the peopling of India: An exploratory study
      based on the available prehistoric, linguistic and biological evidences.
AB  - Among the most contentious currently debated issues is about the people who had
      settled first in the Indian subcontinent. It has been suggested that the
      communities affiliated to the Austro-Asiatic linguistic family are perhaps the
      first to settle in India and the palaeoanthropological evidences suggest the
      earliest settlement probably around 60,000 years BP. Recent speculations, based
      on both traditional genetic markers and DNA markers, seem to corroborate the
      aforesaid view. However, these studies are inadequate both in terms of the
      representation of the constituent groups within this broad linguistic category as
      well as the number of samples that represent each of them. We strongly feel that,
      before making any formidable conclusions on the peopling of India and/or the
      history of settlement, it is necessary to ascertain that the Austro-Asiatic
      speakers, represented by over 30 different tribal groups, either genetically
      constitute a homogenous single entity or are a heterogeneous conglomeration,
      derived from different sources. As a first step towards this we tried to collate
      and analyse the existing information   geographic, ethno-historic, cultural and
      biological. The results of the analyses of anthropometric and genetic marker data
      indicate that the Austro-Asiatic groups, particularly the Mundari speakers, with
      certain exceptions, show greater homogeneity among them when compared to the
      other linguistic groups, although certain groups show as outliers. However,
      traditional genetic markers show lower within population heterozygosity compared
      to Dravidian and other Indian populations. This is contrary to what has been
      claimed in case of certain DNA markers. Given that relatively greater
      heterozygosity among the Austro-Asiatic populations has been taken as one of the
      important evidences supporting greater antiquity of these populations one should
      await results of detailed DNA studies being currently undertaken by us, involving
      a number of Austro-Asiatic and other ethnic populations of India to resolve the
      issue unequivocally.

PMID- 12799498
TI  - On the origin of differentiation.
AB  - Following the origin of multicellularity in many groups of primitive organisms
      there evolved more than one cell type. It has been assumed that this early
      differentiation is related to size   the larger the organism the more cell types.
      Here two very different kinds of organisms are considered: the volvocine algae
      that become multicellular by growth, and the cellular slime moulds that become
      multicellular by aggregation. In both cases there are species that have only one
      cell type and others that have two. It has been possible to show that there is a
      perfect correlation with size: the forms with two cell types are significantly
      larger than those with one. Also in both groups there are forms of intermediate
      size that will vary from one to two cell types depending on the size of the
      individuals, suggesting a form of quorum sensing. These observations reinforce
      the view that size plays a critical role in influencing the degree of
      differentiation.

PMID- 12799499
TI  - [Migration of cells in allergic inflammation].

PMID- 12799500
TI  - [Vasculitis-focussing allergic granulomatosis angiitis].

PMID- 12799501
TI  - [Effects of Bakumondo-to (Mai-Men-Dong-Tang) on cough sensitivity to capsaicin in
      asthmatic patients with cough hypersensitivity].
AB  - Some patients with bronchial asthma have increased cough sensitivity. In such
      patients coughing may be an inducer of wheeze. The aim of the present study was
      to investigate the effect of Bakumondo-to on the cough sensitivity and
      respiratory tract inflammation in asthmatic patients with increased cough
      sensitivity. In addition influences of intensity of respiratory tract
      inflammation, gender, type of asthma, and disease period on the effect of
      Bakumondo-to on the cough sensitivity were examined. Twenty-one bronchial
      asthmatics whose cough thresholds to capsaicin were less than 3.9 microM were
      examined. METHODS: Cough thresholds to capsaicin (concentration of inhaled
      capsaicin solution causing 5 or more coughs) was measured before and after 2
      months or more treatment with Bakumondo-to (9 g/day, TJ-29). Number of
      eosinophils in peripheral blood, sputum eosinophil ratio, and ECP level in the
      serum were also measured before and after treatment. RESULTS: Bakumondo-to
      significantly increased the cough threshold. Although respiratory tract
      inflammation was not significantly improved, number of eosinophils in peripheral
      blood, sputum eosinophil ratio and ECP level in the serum were remarkably
      decreased more than the half. And Bakumondo-to was more effective in asthmatic
      subjects with severe airway inflammation. Furthermore, a greater effect of it was
      observed in women. A greater effect was also observed in patients having a
      disease duration of less than 1 year. CONCLUSION: Our results suggest that
      Bakumondo-to may be an effective therapeutic preparation for coughing in
      asthmatic patients with cough hypersensitivity.

PMID- 12799502
TI  - Risk factors for bronchiolitis-associated deaths among infants in the United
      States.
AB  - BACKGROUND: Risk factors for bronchiolitis deaths have not been described on a
      national level. We examined the epidemiology of and identified risk factors for
      bronchiolitis-associated deaths among infants in the United States. METHODS:
      Multiple cause-of-death and linked birth/infant death data for 1996 through 1998
      were used to examine bronchiolitis-associated infant deaths. Risk factors were
      assessed by comparing infants who died with bronchiolitis and surviving infants.
      RESULTS: During 1996 through 1998 there were 229 bronchiolitis infant deaths,
      resulting in an average annual infant mortality rate of 2.0 per 100 000 live
      births. The majority (55%) of infant deaths occurred among infants ages 1 through
      3 months. The bronchiolitis mortality rate was highest among infants weighing
      <1500 g at birth (VLBW) as compared with infants weighing 1500 to 2499 g (LBW)
      and > or =2500 g at birth (29.8, 6.4 and 1.3 per 100 000 live births,
      respectively). Sixty-three percent of bronchiolitis deaths were among infants
      weighing > or =2500 g. VLBW and LBW infants remained at an increased risk of
      dying with bronchiolitis after controlling for other risk factors. Other risk
      factors included increasing birth order, low 5-min Apgar score, young maternal
      age, unmarried mother and tobacco use during pregnancy. CONCLUSIONS: VLBW and LBW
      infants are at increased risk of dying with bronchiolitis, even when taking into
      account other risk factors. Although infants weighing <2500 g at birth are at
      increased risk for dying with bronchiolitis, the majority of bronchiolitis deaths
      occur among infants of normal birth weight.

PMID- 12799503
TI  - Prospective incidence study of nosocomial infections in a pediatric intensive
      care unit.
AB  - BACKGROUND: Nosocomial infections are important causes of substantial morbidity,
      mortality and prolonged hospital stay in pediatric intensive care units (PICU).
      METHODS: A prospective surveillance study was performed in the PICU at a
      university hospital in Barcelona during the 6 months from May through October
      2000 to describe the epidemiologic profile of nosocomial infections. Centers for
      Disease Control and Prevention criteria were used as standard definitions for
      nosocomial infections. Data including extrinsic risk factors (invasive devices)
      associated with nosocomial infections were recorded and device-associated
      infections were calculated for the specific site. RESULTS: During the study
      period 257 patients were admitted; 15.1% (39) patients had a total of 58
      nosocomial infections. The incidence of nosocomial infection was 1.5 per 100
      patient-days. Patients with cardiac surgery had the highest nosocomial infection
      rate, 2.3 per 100 patient-days. Bacteremia (51.7%), respiratory infection (19.0%)
      and urinary tract infection (17.2%) were the most frequent nosocomial infections
      observed, and these were associated with use of invasive device. Coagulase
      negative staphylococci (39%) and Pseudomonas aeruginosa (24%) were the most
      common organisms isolated. Nosocomial infection rates per 1000 device days were
      23.9 for respiratory infection, 12.4 for bacteremia and 10.7 for urinary tract
      infection. The durations of hospitalization for patients with and without
      infection were 22.5 and 9 days, respectively (P < 0.001). CONCLUSIONS:
      Performance of surveillance highlights the importance of nosocomial infections
      and their influence in the hospital stay and can guide selection of prevention
      and control measures to reduce morbidity and mortality in a PICU.

PMID- 12799504
TI  - Factors associated with hand hygiene practices in two neonatal intensive care
      units.
AB  - OBJECTIVE: To determine whether hand hygiene practices differ between levels of
      contact with neonates; to characterize the hand hygiene practices of different
      types of personnel; and to compare hand hygiene practices in neonatal intensive
      care units (NICUs) using different products. METHODS: Research assistants
      observed staff hand hygiene practices during 38 sessions in two NICUs. Patient
      touches were categorized as touching within the neonates' environment but only
      outside the Isolette (Level 1), touching within the Isolette but not the neonate
      directly (Level 2) or directly touching the neonate (Level 3). Hand hygiene
      practices for each touch were categorized into five groups: cleaned hands and new
      gloves; uncleaned hands and new gloves; used gloves; clean hands and no gloves;
      uncleaned hands and no gloves. RESULTS: Research assistants observed 1472
      touches. On average each neonate or his or her immediate environment was touched
      78 times per shift. Nurses (P = 0.001), attending physicians (P = 0.02) and
      physicians-in-training (P = 0.03) were more likely to use appropriate practices
      during Level 3 touches, but only 22.8% of all touches were with cleaned and/or
      newly gloved hands. The mean number of direct touches by staff members with
      cleaned hands was greater in the NICU using an alcohol-based hand rub than in the
      NICU using antimicrobial soap (P < 0.01). CONCLUSIONS: Hand hygiene was
      suboptimal in this high risk setting; administrative action and improved products
      may be needed to assure acceptable practice. In this study use of an alcohol
      based product was associated with significantly improved hand hygiene and should
      be encouraged, as recommended in the new CDC hand hygiene guideline.

PMID- 12799505
TI  - Incidence and etiologies of complicated parapneumonic effusions in children, 1996
      to 2001.
AB  - BACKGROUND: The incidence and causative organisms associated with complicated
      parapneumonic effusions in children with community-acquired pneumonia are likely
      to have changed during the past several years. METHODS: Data regarding clinical
      and laboratory features were abstracted retrospectively from medical records of
      76 subjects with complicated parapneumonic effusions at a tertiary children's
      hospital from 1996 through 2001. Incidence rates per 10 000 hospital discharges
      and per 1000 patients with nonviral pneumonia were calculated. RESULTS: Etiologic
      organisms were Streptococcus pneumoniae (31 subjects), Staphylococcus aureus (7),
      Streptococcus pyogenes (5), Abiotrophia sp. (1) and no culture-confirmed agent
      (32). The annual incidence of complicated parapneumonic effusions per 10 000
      discharges progressively increased from 4.5 in 1996 to 25.0 in 1999 (P = 0.0001),
      then declined to 10.1 in 2001 (P = 0.03). Similarly the incidence per 1000 cases
      of nonviral pneumonia increased from 2.9 in 1996 to 11.0 in 1999 (P = 0.003) and
      then declined to 4.8 in 2001 (P = 0.053). Whereas S. pneumoniae was the leading
      confirmed etiology in each year, the proportion of cases caused by Staphylococcus
      aureus increased from 6% in 1996 to 2000 (all of which were methicillin
      susceptible) to 30% in 2001 (all methicillin-resistant; P = 0.04). CONCLUSIONS:
      The incidence of complicated parapneumonic effusions in children with community
      acquired pneumonia increased from 1996 to 1999 and then declined concomitant with
      the introduction of the pneumococcal conjugate vaccine. Although cases caused by
      S. pneumoniae have decreased, community onset methicillin-resistant
      Staphylococcus aureus has emerged as a cause of pneumonia with complicated
      effusions in children.

PMID- 12799506
TI  - Treatment of children with congenital cytomegalovirus infection with ganciclovir.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection affects approximately 1%
      of live births in the US. Ten percent of these infants have symptoms at birth and
      another 10 to 15% acquire hearing loss or developmental problems. Congenital CMV
      is the most common cause of nonhereditary sensorineural hearing loss in children,
      and progressive hearing loss is common. To arrest the natural progression of
      congenital CMV, children referred to our center were treated with a prolonged
      course of ganciclovir. METHODS: Medical records of children with congenital CMV
      who were treated with ganciclovir were reviewed to tabulate their presenting
      symptoms, duration of treatment, audiologic and developmental assessments and
      complications. RESULTS: We treated nine children with symptomatic CMV with iv
      ganciclovir at a median age of 10 days (range, 3 days to 11 months). Findings at
      diagnosis included microcephaly (five of nine); petechiae (five of nine);
      thrombocytopenia (seven of nine); and intracranial calcifications (six of eight).
      Hearing loss was noted before therapy in five of nine. The median duration of iv
      and subsequent oral ganciclovir was 1 year and 0.83 year, respectively. Median
      follow-up was 2 years (range, 1 to 7 years). No child had progression of hearing
      loss; improvement occurred in two. Seven children had at least one complication
      of ganciclovir therapy: central venous catheter/site infection (six); catheter
      malfunction (three); and neutropenia (one). CONCLUSION: Of nine children none
      treated with ganciclovir for congenital CMV had detectable progressive hearing
      loss. Complications associated with iv therapy occurred frequently. Currently
      available oral analogues of ganciclovir may facilitate earlier and more prolonged
      therapy for children with symptomatic congenital CMV and should be subjected to
      randomized controlled trials.

PMID- 12799507
TI  - Can acute otitis media caused by Haemophilus influenzae be distinguished from
      that caused by Streptococcus pneumoniae?
AB  - BACKGROUND: Previous limited data suggest that acute otitis media (AOM) caused by
      Streptococcus pneumoniae can present as a more severe disease than that caused by
      Haemophilus influenzae or Moraxella catarrhalis, as expressed by both tympanic
      membrane and systemic findings. OBJECTIVES: To evaluate the severity of disease
      and impact of various pathogens, age, disease history and previous antibiotic
      therapy in children with AOM by using a comprehensive clinical/otologic score.
      PATIENTS AND METHODS: The study group consisted of 372 children ages 3 to 36
      months with AOM seen at the pediatric emergency room during 1996 through 2001.
      All patients had tympanocentesis and middle ear fluid culture performed at
      enrollment. Clinical status was determined by a clinical/otologic score
      evaluating severity (0 = absent to 3 = severe) of tympanic membrane findings
      (redness and bulging) and patient's fever, irritability and ear tugging. Maximal
      severity score was 15. RESULTS: There were 138 (37%) H. influenzae, 76 (21%) S.
      pneumoniae, 64 (17%) mixed infections (H. influenzae + S. pneumoniae) and 94
      (25%) culture-negative cases. The overall clinical/otologic score was higher in
      culture-positive than in culture-negative patients (9.27 +/- 2.75 vs.8.38 +/-
      3.08, P = 0.01). When analyzed by age groups, this difference was significant
      only for the youngest age group (3 to 6 months, P = 0.05). The severity scores
      for AOM caused by H. influenzae and S. pneumoniae were significantly higher than
      in the culture-negative AOM when tympanic membrane redness and bulging were
      analyzed separately. No differences were recorded in clinical/otologic scores
      between different pathogens (9.49 +/- 2.86, 9.03 +/- 2.72 and 9.09 +/- 2.54 for
      H. influenzae, S. pneumoniae and H. influenzae + S. pneumoniae, respectively).
      The mean clinical/otologic score was higher in culture-positive than in culture
      negative patients without relationship to previous antibiotic treatment or number
      of previous AOM episodes. CONCLUSIONS: (1) The clinical/otologic score of culture
      positive young infants was higher than that of culture-negative infants; (2) the
      severity of tympanic membrane redness and bulging were the most indicative
      factors discriminating between a bacterial and nonbacterial etiology of AOM; and
      (3) the use of a clinical/otologic score could not discriminate among various
      bacterial etiologies of AOM.

PMID- 12799508
TI  - Review of randomized controlled trials on pneumococcal vaccination for prevention
      of otitis media.
AB  - BACKGROUND: Increasing resistance to antibiotics of the pathogens causing acute
      otitis media (AOM) emphasize the need for effective methods to prevent episodes
      of otitis media in young children. OBJECTIVE: To assess the effectiveness of
      pneumococcal vaccination for prevention of AOM in children age 12 years and
      younger. METHODS: Systematic review of 11 randomized controlled trials including
      46 074 children in whom pneumococcal vaccination against AOM was compared with a
      control treatment. Vaccine effect was estimated as a rate ratio (RR): AOM
      episodes per child month in pneumococcal vaccination group divided by the AOM
      episodes per child-month in control group. RESULTS: A moderate effect of
      pneumococcal polysaccharide vaccination was found in children 24 months of age
      and older [RR 0.78; 95% confidence interval (CI) 0.63 to 0.97]. Pneumococcal
      polysaccharide vaccine had little effect on prevention of AOM in children without
      previous documented episodes before vaccination (RR 0.92; 95% CI 0.85 to 0.99).
      Better efficacy was seen in those children with documented prior AOM before
      vaccination (RR 0.81; 95% CI 0.72 to 0.91). Pooled results of pneumococcal
      conjugate vaccine trials in infants vaccinated as early as 2 months of age and in
      toddlers attending day care showed only a small effect on prevention of AOM (RR
      0.92; 95% CI 0.85 to 0.99). CONCLUSION: Based on these results, a large scale
      pneumococcal vaccination program for a primary indication of preventing AOM in
      infancy is not indicated. The results of ongoing trials should provide more
      information whether the conjugate vaccine is effective in high risk (otitis
      prone) children after 1 year of age.

PMID- 12799509
TI  - Vaccination of day-care center attendees reduces carriage of Streptococcus
      pneumoniae among their younger siblings.
AB  - AIM: We conducted a study to determine whether administration of a pneumococcal
      conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent
      acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their
      younger siblings. METHODS: In a double blind study, 262 DCC attendees ages 12 to
      35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine
      (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It
      was planned to follow the groups for 2 years with monthly nasopharyngeal
      pneumococcal cultures during the first follow-up year and every 2 months during
      the second year. Forty-six younger siblings of the above described children, age
      <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were
      also enrolled, and nasopharyngeal cultures were obtained monthly until the
      children reached the age of 18 months or started to attend DCC, if before the age
      of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic
      susceptibility. RESULTS: Of the 3748 cultures obtained from the DCC attendees,
      2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the
      younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures
      were significantly less frequently positive for the VT S. pneumoniae than among
      the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in
      the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs.
      34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in
      both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger
      siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease
      in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9
      recipients and their younger siblings. The relative risks (and 95% confidence
      intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or
      =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9
      recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to
      0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired,
      VT and antibiotic-resistant S. pneumoniae were carried for a significantly
      shorter period of time among siblings of PnCRM9 recipients than in siblings of
      controls. CONCLUSION: The marked effect of PnCRM9 administration to DCC attendees
      on carriage of VT and antibiotic-resistant S. pneumoniae among their younger
      household close contacts demonstrates a herd effect of the vaccine.

PMID- 12799510
TI  - Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant
      Streptococcus pneumoniae in day-care centers.
AB  - BACKGROUND: In the developed societies, day-care centers (DCCs) play an important
      role in the spread of antibiotic-resistant pneumococci both within the facility
      and from the facility to the community. This study was conducted to determine the
      effect of a nonavalent pneumococcal conjugate vaccine (PCV-9) on the carriage of
      antibiotic-resistant pneumococci in the DCC. SUBJECTS AND METHODS: Healthy DCC
      attendees ages 12 to 35 months were randomized to receive either PCV-9 or a
      control vaccine (conjugate meningococcus C vaccine) in a double blinded manner.
      Nasopharyngeal Streptococcus pneumoniae cultures were obtained from each subject
      before vaccination, monthly during the first year of follow-up and every 2 to 3
      months during the second year of follow-up. For each isolate the serotype and
      antibiotic susceptibility were determined. RESULTS: A total of 132 and 130
      evaluable toddlers received either PCV-9 or the control vaccine, respectively. In
      total 3748 cultures were obtained, of which 2450 (65%) were positive for S.
      pneumoniae. The resistance rates to penicillin, trimethoprim-sulfamethoxazole and
      erythromycin were 36, 35 and 16%, respectively. Resistance rates to > or =1 and >
      or =3 antibiotic categories were 52 and 9%, respectively. Antibiotic resistance
      was found mainly in the 5 serotypes included in the pneumococcal conjugate
      vaccines (6B, 9V, 14, 19F and 23F) and in 2 related serotypes (6A and 19A). In
      the vaccinated group a clear and significant reduction of the carriage rate of
      the serotypes included in the vaccine and the related serotype 6A as well as an
      increase in the carriage rate of the serotypes not included in the vaccine were
      observed. In parallel a significant decrease in carriage rate of antibiotic
      resistant pneumococci was observed. The reduction of carriage of antibiotic
      resistant pneumococci was seen in all age windows but was greater in the age
      window <36 months. CONCLUSIONS: The carriage rate of antibiotic-resistant S.
      pneumoniae, including multiply resistant S. pneumoniae, in DCC attendees is high.
      Pneumococcal conjugate vaccines seem to be an important tool for reducing the
      carriage rate of antibiotic-resistant pneumonia in DCCs.

PMID- 12799512
TI  - Optimizing blood culture practices in pediatric immunocompromised patients:
      evaluation of media types and blood culture volume.
AB  - BACKGROUND: The optimal use of blood cultures to determine the etiology of
      febrile episodes in neutropenic children has not been well-defined. METHODS:
      Single volume blood cultures using the Pediatric ISOLATOR System (ISO), were
      compared with variable, weight-based culture volumes using the BACTEC 9240
      Culture System (BAC). Additionally the value of routinely inoculating the BACTEC
      MYCO/F LYTIC culture vial (MFL) as well as the BACTEC AEROBIC/F culture vial (AF)
      was examined. RESULTS: A total of 2620 cultures had both ISO and BAC inoculated;
      182 cultures were positive (7.0% of cultures); 97.8% of positive cultures were
      detected by the BAC (AF and/or MFL) vs.46.2% detected by the ISO. The advantage
      of the BAC over the ISO was statistically significant for overall recovery of
      isolates and bloodstream infections, including most individual organism
      categories. There were only two instances (one each of histoplasmosis and
      candidemia) in which a blood stream infection was detected by ISO only. All the
      isolates judged to be contaminants were recovered by BAC only. AF detected
      significantly more coagulase-negative Staphylococcus spp. than the MFL. Of the
      isolates 16%, representing 14% of the bloodstream infections (including Gram
      negative infections), were detected by the MFL only. Infections were detected
      more quickly by BAC than by ISO (P < 0.0001). Among the BAC media types, AF was
      faster than MFL (P < 0.0001). CONCLUSIONS: Optimal yield of blood cultures in
      immunocompromised pediatric patients included the use of BAC with a weight-based,
      graduated volume of culture inoculation and routine use of both AF and MFL.

PMID- 12799511
TI  - Impact of palivizumab prophylaxis on respiratory syncytial virus hospitalizations
      in high risk Alaska Native infants.
AB  - BACKGROUND: Alaska Native children experience extremely high rates of
      hospitalization for respiratory syncytial virus (RSV) infection. We evaluated the
      effect of palivizumab prophylaxis on the incidence of RSV hospitalizations in
      high risk Alaska Native children. METHODS: We analyzed two retrospective cohorts.
      The first analysis, of southwest Alaska Native children hospitalized with acute
      respiratory infections during 1993 to 1996 and 1998 to 2001, compared RSV
      hospitalization rates among premature and nonpremature infants born before (1993
      to 1996) and after (1998 to 2001) palivizumab use. The second analysis, of Alaska
      Native infants with a history of prematurity or lung disease during 1998 through
      2001, compared RSV hospitalization among children receiving palivizumab during
      protected periods (within 32 days after a dose of palivizumab) and unprotected
      periods. RESULTS: First RSV hospitalizations in premature infants from southwest
      Alaska meeting criteria for palivizumab prophylaxis decreased from 439 per 1000
      births before to 150 per 1000 births after palivizumab (relative rate, 0.34; 95%
      confidence interval, 0.17 to 0.68), whereas the rate in nonpremature infants
      remained stable (148 per 1000 births compared with 142 per 1000). Among high risk
      Alaska Native children during 1998 through 2001, the rate of first RSV
      hospitalization was 0.55 per 1000 protected days and 1.07 per 1000 unprotected
      days (relative rate, 0.52; 95% confidence interval, 0.28 to 0.93). CONCLUSIONS:
      Palivizumab reduced RSV hospitalizations in high risk infants in a region with
      high rates of RSV hospitalization.

PMID- 12799513
TI  - Preventing mother-to-child transmission of human immunodeficiency virus type 1 in
      resource-poor countries.

PMID- 12799514
TI  - Combination antifungal therapy.

PMID- 12799515
TI  - HACEK endocarditis in infants and children: two cases and a literature review.
AB  - We report 2 cases of Haemophilus parainfluenzae endocarditis and review 34 cases
      of HACEK endocarditis from the literature. HACEK organisms are the most common
      cause of Gram-negative endocarditis in children. They have a propensity to form
      friable vegetations (especially H. parainfluenzae) that break off and cause
      symptomatic emboli. HACEK endocarditis (from a review of the 36 published cases)
      may involve previously normal hearts (33%), may be complicated by embolization
      (31%) and may require vegetectomy or other surgery (31%). Mortality with HACEK
      endocarditis was 14%. HACEK organisms may be resistant to penicillins but are
      susceptible to third generation cephalosporins.

PMID- 12799516
TI  - Risks to children of health care personnel receiving smallpox vaccination.

PMID- 12799517
TI  - Topical imiquimod for molluscum contagiosum in T cell immunodeficiency.

PMID- 12799518
TI  - Cryptococcal meningitis in a child with acute lymphoblastic leukemia.

PMID- 12799519
TI  - Nerve growth factor attenuates hippocampal cholinergic deficits and operant
      learning impairment in rats with entorhinal cortex lesions.
AB  - In the present study we investigated whether continuous intraventricular nerve
      growth factor (NGF) infusion could ameliorate hippocampal cholinergic deficits
      and learning impairment following entorhinal cortex lesions. Rats with such
      lesions received continuous intraventricular infusions of NGF or vehicle.
      Unlesioned rats with a sham operation were studied as controls. After learning
      sessions, a dialysis probe was implanted in the CA3 hippocampal region. In
      addition, brain sections were stained for synaptophysin immunoreactivity. In rats
      undergoing surgical procedures similar to those in the behavioral study, brains
      were processed for acetylcholinesterase (AChE) histochemistry. NGF-treated rats
      showed partial amelioration of lesion-associated hippocampal acetylcholine (ACh)
      efflux deficits and fixed-interval schedule learning impairment compared with
      vehicle-treated rats. Histochemical, immunohistologic, and microdensitometric
      analyses confirmed greater density of AChE-positive fibers and synaptophysin
      immunoreactivity in CA3, in NGF-treated rats relative to vehicle-treated rats,
      although not as great as in sham-operation rats, indicating partial recovery in
      NGF-treated rats. These results suggest that enhanced performance of the learning
      task with NGF treatment was related to improved hippocampal cholinergic function:
      specifically, increased cholinergic neurotransmission resulting from NGF effects
      on cholinergic neurons and presynaptic terminals.

PMID- 12799520
TI  - Effects of chronic caffeine pre-exposure on conditioned and unconditioned
      psychomotor activity induced by nicotine and amphetamine in rats.
AB  - Three experiments examined the effects of chronic pre-exposure to caffeine on the
      subsequent conditioned and unconditioned locomotor activating effects of nicotine
      or amphetamine in rats. Rats were given daily intraperitoneal injections of
      caffeine anhydrous (0, 10 or 30 mg/kg base) for 30 days. Conditioning
      (environment-drug pairings) began after the last day of caffeine pre-exposure.
      Pre-exposure to 30 mg/kg of caffeine enhanced the acute and chronic locomotor
      effects of amphetamine (0.5 mg/kg). A similar enhancement of activity was not
      seen with the high (0.421 mg/kg base) or low dose (0.175 mg/kg) of nicotine. In a
      drug-free test, the distinct environment paired with amphetamine and the high
      dose of nicotine evoked increases in activity relative to controls. Caffeine pre
      exposure did not affect expression of this conditioned hyperactivity. These
      effects of caffeine pre-exposure on amphetamine-induced activity could not be
      attributed to non-specific effects of caffeine.

PMID- 12799521
TI  - Behavioural changes in rats treated with a neurotoxic dose regimen of
      dextrorotatory amphetamine derivatives.
AB  - Repeated administration of amphetamine derivatives is reported to induce
      neurotoxicity in rat brain. Methamphetamine (MA) impairs the function of both the
      dopaminergic and serotonergic systems, 3,4-methylenedioxymethamphetamine (MDMA,
      Ecstasy) affects primarily the latter system. The neurochemical deficits induced
      by these amphetamines have been described in detail, but relatively few data have
      been reported regarding the behavioural consequences of the neurotoxic treatment.
      The aim of the present study was to investigate short- and long-term behavioural
      consequences of treatment with neurotoxic doses of (+)MA or (+)MDMA. Spontaneous
      locomotor activity in novel surroundings and cognitive function (avoidance
      behaviour) were evaluated. Rats were treated with four s.c. injections of 10
      mg/kg (+)MA or (+)MDMA with a 2-hour interval between each injection. Behavioural
      tests were then carried out 3 days, 1, 2 and 4 weeks after these treatments. A
      reduction of spontaneous locomotor activity in novel surroundings was detected 3
      days after the treatment with the study drugs, but not after 1, 2 and 4 weeks. No
      change in passive and active avoidance learning was observed. The lack of marked
      behavioural changes after a neurotoxic dose regimen indicates that some
      compensatory mechanisms may develop and counterbalance the neurochemical changes
      induced by these amphetamine compounds.

PMID- 12799522
TI  - Cholinergic modulation of memory in the basolateral amygdala involves activation
      of both m1 and m2 receptors.
AB  - Muscarinic cholinergic activation is a critical component of basolateral amygdala
      (BLA)-mediated modulation of memory consolidation. The receptor(s) mediating this
      activation during consolidation have not been elucidated. This study investigated
      the roles of muscarinic subtype 1 (m1) and subtype 2 (m2) receptors in memory
      enhancement, by post-training intra-BLA infusions of the non-selective muscarinic
      agonist oxotremorine. Rats received intra-BLA infusions of either oxotremorine
      alone (10 microg in 0.2 microl per side), oxotremorine together with the
      selective m1 antagonist telenzipine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine
      with the selective m2 antagonist methoctramine (1.7, 5.0, 17 or 50 nmol/side),
      oxotremorine with a combination of the above doses of telenzipine and
      methoctramine, or only vehicle, immediately after inhibitory avoidance training.
      Performance on a 48-hour retention test was significantly enhanced in
      oxotremorine-treated rats relative to vehicle-infused controls. Intra-BLA co
      infusion of oxotremorine with either telenzipine (5, 17 or 50 nmol/side) or
      methoctramine (17 or 50 nmol/side) blocked the oxotremorine-induced enhancement.
      Combinations of these antagonists did not act additively to block memory
      enhancement by oxotremorine. These findings indicate that modulation of memory
      consolidation induced by cholinergic influences within the BLA requires
      activation of both m1 and m2 receptor synapses. Plausible mechanisms for m1- and
      m2-mediated influences on BLA circuitry are discussed.

PMID- 12799523
TI  - A comparison of drug effects in latent inhibition and the forced swim test
      differentiates between the typical antipsychotic haloperidol, the atypical
      antipsychotics clozapine and olanzapine, and the antidepressants imipramine and
      paroxetine.
AB  - Current animal models of antipsychotic activity that have the capacity to
      dissociate between typical and atypical antipsychotic drugs (APDs) have two
      drawbacks: they require previous administration of a psychotomimetic drug, and
      they achieve the dissociation by demonstrating effectiveness of atypical but not
      typical APDs, thus losing specificity and selectivity for APDs. The present
      experiments were designed to solve these problems by using two non
      pharmacological tests: latent inhibition (LI), in which potentiation of the
      deleterious effects of non-reinforced stimulus pre-exposure on its subsequent
      conditioning served as a behavioral index for a common action of typical and
      atypical APDs (antipsychotic), and the forced swim test (FST), in which reduction
      of immobility served as a behavioral index for a dissimilar action of these drugs
      (antidepressant). The typical APD haloperidol (0.1 mg/kg), the atypical APDs
      clozapine (2.5 mg/kg) and olanzapine (0.6 mg/kg), and the antidepressants
      imipramine (10 mg/kg) and paroxetine (7.0 mg/kg), produced distinct patterns of
      action in the two tests: haloperidol potentiated LI and increased immobility in
      the FST, clozapine and olanzapine potentiated LI and decreased immobility in the
      FST, and imipramine and paroxetine decreased immobility in the FST and did not
      potentiate LI. Thus, the comparison of drug effects in LI and FST enabled a
      discrimination between typical and atypical APDs without losing selectivity for
      APDs.

PMID- 12799524
TI  - Comparison of the discriminative-stimulus effects of SKF 38393 with those of
      other dopamine receptor agonists.
AB  - The dopamine D(1)-like receptor agonists have traditionally been defined
      molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence
      correlating the effectiveness of these drugs in behavioral assays and their
      effectiveness biochemically has not been forthcoming. The present study compared
      the discriminative-stimulus effects of the D(1)-like partial agonist SKF 38393
      with several other D(1)-like agonists, an indirect agonist, cocaine, and a D(2)
      like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response
      schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule,
      30 consecutive responses on one of two keys were reinforced with food
      presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30
      consecutive responses on the alternative key were reinforced after saline
      injection. When daily performances were stable, substitution patterns for several
      compounds were assessed during test sessions in which 30 consecutive responses on
      either key were reinforced. Quinpirole and cocaine each produced saline
      appropriate responding. In contrast, the D(1)-like agonists, SKF 75670 and SKF
      77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered
      a full agonist based on adenylyl cyclase assays, was less effective in
      substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the
      partial agonist SKF 75670. The present results suggest that second messenger
      effects other than stimulation of adenylyl cyclase may play an important role in
      the behavioral effects of dopamine D(1)-like agonists.

PMID- 12799525
TI  - Role of the NMDA receptor NR2B subunit in the discriminative stimulus effects of
      ketamine.
AB  - The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is
      a dissociative anesthetic with antihyperalgesic properties. However, its clinical
      use is compromised by psychotomimetic side-effects. As ketamine and other
      noncompetitive NMDA antagonists, such as phencyclidine and dizocilpine, are not
      selective for the NR2A-2D subunits of the NMDA receptor, it is unclear which of
      these subunits is responsible for the psychotomimetic side-effects. This study
      investigated the role of the NR2B subunit in the ketamine drug discrimination
      model, a possible correlate for such side-effects. In a first experiment aimed at
      assessing general potency and time dependency, ketamine, dizocilpine,
      phencyclidine and the NR2B-selective antagonists ifenprodil and Ro 25-6981, dose
      dependently suppressed fixed ratio 10 food-reinforced responding in rats, with
      peak efficacy obtained around 15-40 min. In rats trained to discriminate ketamine
      from vehicle in a two-lever fixed ratio 10 food-reinforced procedure, ketamine,
      dizocilpine, phencyclidine and Ro 25-6981 induced complete generalization (>80%);
      whereas ifenprodil induced partial generalization (33%). These findings suggest
      that the NR2B subunit is involved in the discriminative stimulus effects of
      noncompetitive NMDA antagonists, and that selective NR2B antagonists may also
      induce psychotomimetic side-effects.

PMID- 12799526
TI  - Effects of memantine, an NMDA receptor antagonist, on place preference
      conditioned with drug and nondrug reinforcers in mice.
AB  - Antagonists of the N-methyl-D-aspartate (NMDA) receptor complex have been shown
      to inhibit the expression of place preferences conditioned with several drugs
      that are abused by humans, which suggests that this class of compounds may be
      beneficial in the treatment of substance dependence. Therefore it is important to
      assess the specificity of this effect, of whether inhibitory effects of NMDA
      receptor antagonists on conditioned drug stimuli generalize to behaviors produced
      by nondrug reinforcers. The present study was designed to compare the effects of
      the NMDA receptor channel blocker, memantine, on the expression of place
      preferences conditioned with: (1) consumption of regular laboratory food; (2)
      sexual encounters with females; and (3) injection of morphine (10 mg/kg) in adult
      male Swiss mice. For all three experiments reported here, unconditioned stimuli
      (food, receptive female or morphine) were presented before the exposures to the
      "to-be-conditioned" environments. Significant place preferences developed as a
      result of explicit pairings of the environmental context and food consumption,
      sexual encounter and morphine administration. Memantine (7.5 mg/kg, given prior
      to the post-conditioning test) inhibited the expression of place preferences
      conditioned with morphine and sexual encounter, but had no effects in food
      conditioned mice. These findings suggest that the effects of NMDA receptor
      blockade may not be limited to drug-reinforced behaviors.

PMID- 12799527
TI  - NMDA-receptor antagonism via dextromethorphan and ifenprodil modulates graded
      anxiety test performance of C57BL/6 mice.
AB  - The majority of N-methyl-D-aspartate receptors (NMDA-R) in the adult forebrain
      are di- or triheteromers composed of NR1, NR2A and NR2B subunits. Subunit non
      selective NMDA-R antagonists produce anxiolytic-like effects together with motor
      and sensory side-effects. The graded anxiety test (GAT), permits the within-task
      distinction of drug effects on anxiety from those on activity and perception. By
      testing NMDA-R subunit selective agents in the GAT it might be possible to
      determine whether their effects on anxiety, activity and perception are
      interrelated, and whether separate NMDA-R subtypes are involved. Dextromethorphan
      (weakly NR2A-selective) (10 and 30 mg/kg, i.p.) and ifenprodil (highly NR2B
      selective) (1, 3 and 5 mg/kg, i.p.) were tested in the GAT. Both drugs failed to
      induce anxiolysis devoid of side-effects. However, the 10 mg/kg dose of
      dextromethorpan showed an anxiolytic, whereas the 30 mg/kg dose showed an
      anxiogenic, behavioral profile. Since the selective blockade of the NR2B subunit
      by ifenprodil had no clear anxiolytic effect, the anxiolytic potential of NMDA
      subunit non-selective agents might involve NR2A-containing receptors.

PMID- 12799528
TI  - Haloperidol-induced dyskinesia is associated with striatal NO synthase
      suppression: reversal with olanzapine.
AB  - The underlying pathophysiological basis of tardive dyskinesia (TD) remains
      speculative. Haloperidol (HP) inhibits neuronal nitric oxide (NO) synthase (NOS)
      activity in vitro, but has not to date been studied in an intact animal model.
      Recent animal studies have found that extrapyramidal dysfunction evoked by
      chronic HP is associated with suppression of striatal cyclic guanosine
      monophosphate (cGMP), as well as plasma nitrogen oxides. Striatal dopamine (DA)
      is central to motor control, while NO plays an important neuroregulatory role in
      striatal DA function. Recent case reports suggest that atypical antipsychotics,
      such as olanzapine (OLZ), may be effective in reversing TD. Here, rats treated
      with HP (1.5 mg/kg per day p.o.) for 28 days developed significant vacuous
      chewing movements (VCMs) together with significant suppression of striatal NOS
      activity. Acute challenge with OLZ (1 and 2 mg/kg i.p.) significantly reversed
      both HP-induced VCMs and suppression of striatal NOS activity. Therefore TD may
      involve attenuation of NO-mediated neuromodulation in the striatum. Reversal of
      VCMs and NOS suppression with OLZ suggests that disinhibition of striatal NOS
      activity may underlie the clinical benefit of OLZ in TD.

PMID- 12799530
TI  - Hairy cell leukemia: an update.
AB  - Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder
      comprising approximately 2 to 3% of all adult leukemias in the United States.
      Hairy cells are clonal expansions of mature, activated B-cells. They co-express
      CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal
      immunoglobulin gene rearrangements and express monoclonal surface immunoglobulin
      of either IgG or multiple heavy-chain isotypes. Treatment of hairy cell leukemia
      should be considered for symptomatic patients. It is indicated in patients with
      significant neutropenia, anemia, thrombocytopenia, symptomatic splenomegaly,
      constitutional symptoms due to hairy cell leukemia, or recurrent serious
      infections. Many treatments exist, including cladribine, pentostatin, interferon
      alpha, splenectomy, rituximab (mabthera), and BL-22 immunotoxin.

PMID- 12799531
TI  - Expression and a role of CD30 in regulation of T-cell activity.
AB  - CD30 receptor has been known for almost 20 years, but its expression and activity
      are still the subject of many investigations. Its expression was found in
      different malignancies, and most of the studies regarding CD30 focus on its role
      in lymphomas. The progress that has already been made in this field is reflected
      in implementation of CD30 as a target for immunotoxin, which has been tested in
      phase I study in treating Hodgkin lymphoma. CD30 is present also on normal,
      activated T cells of all cytokine profiles. However, increased density of CD30
      and CD30-mediated Th2 cytokine production provide evidence of its role in
      determining the activity of T cells toward synthesis of cytokines and involvement
      in reactions of Th2 characteristics. Pleiotropic signaling mediated by CD30 does
      not implicate this receptor just as a cytokine costimulator; it proves to be
      important in several different activities of T cells.

PMID- 12799532
TI  - Recent advances on the role of CD40 and dendritic cells in immunity and
      tolerance.
AB  - CD40 is a key signaling pathway for the function of B cells, monocytes, and
      dendritic cells in the immune system, and plays an important role in inflammatory
      pathways of nonhemopoietic cells. The NFkappaB family of transcription factors is
      a critical mediator in inflammation. NFkappaB is involved both in the regulation
      of CD40 expression and in cell signaling after CD40 ligation. This positive
      feedback loop linking NFkappaB and CD40 plays an important role in the control of
      the adaptive immune response, with fundamental implications for immunity and
      tolerance in vivo.

PMID- 12799533
TI  - HIV receptors on lymphocytes.
AB  - Human immunodeficiency virus infection, despite tremendous efforts in research
      and prevention, is spreading at an increasing speed, especially in developing
      countries. Currently available therapeutic approaches significantly extend the
      lifespan of HIV-infected people, but their use is associated with a severe drug
      regimen, several undesirable side effects, and high cost. Therefore, the
      scientific community is steadfastly pursuing novel strategies for inhibiting
      viral replication, promoting a better immune response, and developing an
      effective vaccine. Recent research on HIV receptors has introduced new concepts
      in the field, showing that expression of receptors, although necessary for virus
      entry, is subordinate to quality of expression, so that efficient infection
      occurs when receptors are properly colocalized. In addition, intracellular
      signaling triggered by HIV receptors has been shown to play important roles in
      pathogenesis by inducing apoptosis of bystander cells. Induction of some pathways
      of intracellular signaling, however, can instead suppress HIV replication, so
      that modulation of these pathways constitutes an additional target to be
      exploited for therapy or vaccines. This article reviews the most exciting aspects
      of these novel findings and discusses their practical application in the fight
      against HIV infection.

PMID- 12799534
TI  - Progress and challenges in the therapy of adult acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia is a heterogeneous disease with distinct biologic
      and prognostic groupings. Although current therapies result in high complete
      remission rates, long-term disease-free survival rates have remained
      disappointingly low. Results from recent studies using risk-tailored approaches
      suggest improvement in overall survival for high-risk groups, such as those with
      Philadelphia chromosome-positive acute lymphoblastic leukemia. Furthermore, the
      incorporation of imatinib mesylate into the treatment regimen for Philadelphia
      chromosome-positive acute lymphoblastic leukemia patients may lead to better
      outcomes. Finally, quantification of minimal residual disease at various time
      points during therapy is being investigated as a means to predict more accurately
      a patient's response to therapy, and to make therapeutic decisions.

PMID- 12799535
TI  - Newly diagnosed childhood acute lymphoblastic leukemia: update on prognostic
      factors and treatment.
AB  - The development of effective therapy for children with acute lymphoblastic
      leukemia is one of the great successes of clinical hematology andoncology. Fifty
      years ago, childhood acute lymphoblastic leukemia was universally fatal, but
      current long-term event-free survival rates are nearly 80%. Despite this improved
      outcome, there are still many challenges facing investigators today. In some
      recent clinical trials, the outcome of "high-risk" patients has approached that
      of "lower risk" patients, suggesting that currently applied clinical factors,
      such as age and presenting leukocyte count, no longer identify the 20% of newly
      diagnosed patients who ultimately will relapse. Additionally, therapy remains
      nonspecific, toxic, and sometimes lethal. As more children with acute
      lymphoblastic leukemia survive into adolescence and adulthood, there is a need to
      address the late sequelae of current therapy and to develop more leukemia
      specific treatments. Promising avenues of research, which may identify
      biologically distinctive subsets of acute lymphoblastic leukemia and potential
      targets for novel therapies, include studies of minimal residual disease,
      lymphoblast genetics (including genetic profiling studies), and host-related
      pharmacogenomics.

PMID- 12799536
TI  - Advances in the therapy of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia therapy has changed dramatically over the past
      decade, with recent studies supporting the use of fludarabine as the initial
      therapy for symptomatic disease. New findings relative to the use of fludarabine
      and complications arising from this therapy are reviewed. Exciting combination
      approaches using monoclonal antibodies such as rituximab or Campath-1H in
      combination with fludarabine offer the opportunity to improve the complete
      response rate further in chronic lymphocytic leukemia. Furthermore, the field of
      experimental therapeutics for chronic lymphocytic leukemia was advanced by the
      description of a new mouse model of human chronic lymphocytic leukemia and
      identification of several disrupted signal transduction pathways in this disease.
      The description of therapies that target AKT, protein kinase C, phosphodiesterase
      4, mammalian target of rapamycin, histone deacetylase, and methyltransferase
      offer the opportunity to utilize molecularly targeted therapy for this disease.
      Such targeted approaches offer hope that we might be on the threshold to changing
      the natural history of chronic lymphocytic leukemia.

PMID- 12799537
TI  - Role of autologous stem cell transplantation in chronic lymphocytic leukemia.
AB  - Autologous hematopoietic stem sell transplantation is increasingly considered for
      treatment of patients with high-risk chronic lymphocytic leukemia. Patients not
      eligible for allogeneic hematopoietic stem cell transplantation with poor
      prognosis disease, documented chemosensitivity, and a minimal tumor burden at the
      time of hematopoietic stem cell transplantation can be treated with autologous
      hematopoietic stem cell transplantation currently using peripheral blood stem
      cells. Different purging methods to obtain sources of stem cells free of tumor
      contamination are currently being evaluated. Major concerns are judicious
      selection of which patients may benefit from this approach, the subsequent risk
      of relapse of disease, and the long-term risk of development of secondary
      malignancies, including myelodysplastic syndrome and acute myelogenous leukemia.
      Recognizing and reducing the risk factors that contribute to relapse and
      complications of the procedure should improve outcome after autologous
      hematopoietic stem cell transplantation. With the increasing use, increasing
      effectiveness, and low treatment-related mortality associated with
      nonmyeloablative conditioning regimens, the question of whether a patient should
      be offered autologous or allogeneic hematopoietic stem sell transplantation can
      be a difficult one. Defining salvage settings for relapse and implementing a
      tandem autologous/allogeneic hematopoietic stem cell transplantation approach may
      provide a method to improve outcome for selected patients.

PMID- 12799538
TI  - Immunobiology of chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia increasingly is being recognized as a useful
      model disease with which to study more general processes involved in the
      evolution of neoplastic disease. The accessibility of the tumor cells and the
      capacity to confirm their clonal relatedness allow for evaluation of the
      processes associated with neoplastic transformation and/or disease progression.
      Recent studies have provided fascinating insight into the potential pathogenesis
      and pathophysiology of this disease. In addition, features of leukemia cells have
      been identified that can distinguish subsets of patients that have different
      tendencies for disease progression. Gene expression studies have identified a
      relatively small number of genes that are differentially expressed between these
      subsets, allowing for focused attention on proteins that might contribute to the
      noted differences in clinical behavior. Finally, recognition that chronic
      lymphocytic leukemia cells depend upon specific microenvironmental growth and
      survival factors identifies novel targets for disease intervention. This article
      focuses on the reports of the past year that have contributed to these areas of
      active research on chronic lymphocytic leukemia, the most common adult leukemia
      in Western societies.

PMID- 12799539
TI  - Comparison of tone burst and tapping evocation of myogenic potentials in patients
      with chronic otitis media.
AB  - OBJECTIVE: Vestibular evoked myogenic potential (VEMP) has recently been broadly
      studied in cochleo-vestibular disorders to elucidate its mechanism. Because it is
      evoked by loud sound stimulation, impairment of the sound transmission through
      the middle ear may affect VEMP results. This study aims to compare the response
      rate of VEMPs using the tone burst method and the tapping method in patients with
      chronic otitis media (COM). DESIGN: Fourteen patients (22 ears) with conductive
      hearing loss due to COM were subjected to VEMP tests using both the tone burst
      method and the tapping method. Each ear was stimulated by a short-tone burst (95
      dB nHL, 500 Hz), followed by tapping on the forehead with a tendon hammer, 200
      times at a frequency of 5 Hz. RESULTS: Thirteen (59%) of the 22 ears showed
      positive VEMPs using the tone burst method, whereas 20 ears (91%) displayed
      positive VEMPs by the tapping method (p < 0.05). The latencies of wave p13 and
      n23, and the amplitude p13-n23 using the tone burst method were 13.4 +/- 4.1
      msec, 20.5 +/- 4.6 msec, and 77.2 +/- 17.2 microV, respectively. These results do
      not significantly differ from those obtained using the tapping method. In ears
      with perforated eardrums (N = 11), five ears (45%) displayed positive VEMPs by
      the tone burst method; compared with nine ears (82%) with positive VEMPs using
      the tapping method, representing a nonsignificant difference. In ears with healed
      eardrums (N = 11), eight ears exhibited positive VEMPs by tone burst, with a mean
      air-bone gap of 25.6 +/- 15.2 dB at 500 Hz, in contrast to a gap of 30.0 +/- 22.9
      dB in three ears without VEMPs, indicating no significant difference.
      CONCLUSIONS: When stimulating sound is attenuated by middle ear pathology, VEMPs
      are expected to be poorly elicited. Under such conditions, myogenic potentials
      may be evoked with the tapping method to elicit the absent VEMPs that result from
      middle ear or inner ear pathology.

PMID- 12799540
TI  - The influence of clicks versus short tone bursts on the vestibular evoked
      myogenic potentials.
AB  - OBJECTIVE: Vestibular evoked myogenic potential (VEMP) has become a diagnostic
      tool to evaluate the integrity of sacculo-collic reflex. To obtain a more
      consistent VEMP response in normal-hearing subjects, we examine whether clicks or
      short tone bursts are more effective in eliciting VEMP responses. DESIGN:
      Prospective study. Twenty-nine normal-hearing volunteers (58 ears) were given
      VEMP tests. Clicks and short tone bursts were presented alternately to evoke
      VEMPs. The latencies of peak p13 and n23, peak-to-peak interval and amplitude
      (p13-n23) were measured and compared. RESULTS: Click stimulation of 57 ears (98%)
      produced VEMPs (C-VEMPs), whereas 51 (88%) revealed positive short tone burst
      evoked VEMPs (STB-VEMPs), exhibiting a significant difference (p < 0.05).
      Furthermore, C-VEMPs displayed shorter latency, longer interval and larger
      amplitude than STB-VEMPs, with a significant difference (p < 0.05), respectively.
      CONCLUSIONS: C-VEMPs had a higher response rate, shorter latency, and larger
      amplitude than STB-VEMPs. These findings suggest that click is superior to short
      tone burst to trigger VEMPs. Because C-VEMPs have a shorter p13 latency than STB
      VEMPs, the interpretation of prolonged latency differs in each stimulus
      condition.

PMID- 12799541
TI  - Hearing loss in children and adults: audiometric configuration, asymmetry, and
      progression.
AB  - OBJECTIVE: The purpose of this study was to characterize the sensorineural
      hearing losses of a group of children and adults along three parameters important
      to the hearing instrument fitting process: 1) audiometric configuration, 2)
      asymmetry of loss between ears, and 3) progression of loss over several years.
      DESIGN: Audiograms for 248 60- and 61-yr-old adults and 227 6-yr-old children
      were obtained from the audiological database at Boys Town National Research
      Hospital. Based on right-ear air-conduction thresholds, the configurations were
      assigned to one of six categories: sloping, rising, flat, u-shaped, tent-shaped,
      and other. Left- and right-ear thresholds were compared to determine asymmetry of
      loss. Progression of loss was evaluated for 132 children for whom additional
      audiograms over an 8-yr period were available. RESULTS: In general, the
      children's hearing losses were more evenly distributed across configuration
      categories while most of the adult's audiograms were sloping or u-shaped in
      configuration. The variability of loss at each frequency was greater for the
      children than the adults for all configuration categories. Asymmetrical losses
      were more common and the degree of asymmetry at each frequency was more extensive
      among the children than the adults. A small number of children showed either
      improved or deteriorated hearing levels over time. In those children for whom
      progressive hearing loss occurred, no frequency was more vulnerable than another.
      CONCLUSIONS: The results of the present study suggest that substantial
      differences in audiological characteristics exist between children and adults.
      Implications for amplification include the development of appropriate fitting
      protocols for unusual audiometric configurations as well as protocols for
      binaural amplification in cases of asymmetric hearing losses.

PMID- 12799542
TI  - Autism and auditory brain stem responses.
AB  - OBJECTIVE: To study a controversy that has been discussed for more than two
      decades: whether or not children with autism have abnormalities affecting the
      cochlear nerve or the auditory pathway in the brain stem and, if so, to describe
      these abnormalities. DESIGN: A group of 153 children and adolescents with
      autistic disorder were included in an investigation of auditory brain stem
      responses (ABR). Two thirds of this group, 101 individuals (75 boys, 26 girls),
      had normal hearing and they were selected for an in-depth ABR study. The results
      from the study group were compared with those of an age-matched comparison group.
      RESULTS: The III-V interpeak latency (IPL) was significantly prolonged in both
      boys and girls with autism, compared with the controls. The latencies of ABR
      waves I and V were also significantly lengthened in the study groups. The
      individual test results showed that more than half of this normal-hearing
      autistic disorder group (58%) had abnormalities of one or more of eight ABR
      parameters studied. The most common abnormalities were prolongation of wave V
      (38%), and of I-V IPL (28%). A lengthening of the I-V IPL was also recorded in
      27% of 49 children who were difficult to test or who had hearing loss. Abnormal
      left-right differences of ABR latencies were found in 18% of autism cases with
      normal hearing. CONCLUSIONS: Possible causes of the reported ABR abnormalities,
      observed here as well as in other studies, are discussed. Brain stem lesion,
      occult cochlear dysfunction, and involvement of the cochlear efferent system are
      probable factors that can explain the ABR findings

PMID- 12799543
TI  - Impact of digital labeling on outcome measures.
AB  - OBJECTIVE: The purpose of this study was to determine whether the label attached
      to the hearing aid being presented would bias outcome measures towards newer
      technological designs. DESIGN: Two groups of subjects participated in this
      investigation. The groups were matched for age, gender, previous hearing aid
      experience, degree and configuration of hearing loss. Group A wore each of two
      digital hearing aids for 1 mo; Group B wore the same digital hearing aid for 2
      mo, but the subjects were given the impression they were changing hearing aids
      after 1 mo. In each group the subjects were told that one of the months they were
      wearing a "digital" hearing aid and one of the months they were wearing a
      "conventional" hearing aid. Outcome measures consisted of a number of behavioral
      speech perception tasks and self-report measures, each completed at the onset and
      after 1 mo use with the hearing aids. RESULTS: Labeling effects were observed for
      many of the outcome measures. Using a mixed-model factorial analysis of variance
      to control for irrelevant variables and to explore interaction terms, prejudice
      (digital versus conventional labeling) was treated as a within-subject factor
      while the subject group (A or B) and clinician were treated as between-subject
      factors. Although only the APHAB RV and BN scales showed significant labeling
      effects on their own, the group of tests used in this study showed a significant
      labeling effect as a whole (p < 0.01). The total influence of labeling and
      related interaction terms indicated labeling-related effects accounted for 2 to
      32% of the variance in individual outcome measures. DISCUSSION: The results of
      this investigation indicate a need for double-blinding in hearing aid research
      aimed at assessing the effectiveness of newer technologies, as well as a need for
      clinicians to critically evaluate the research describing the potential
      advantages of certain circuit options.

PMID- 12799544
TI  - Test-retest reliability of cortical evoked potentials using naturally produced
      speech sounds.
AB  - OBJECTIVE: To determine if naturally produced speech stimuli evoke distinct
      neural response patterns that can be reliably recorded in individuals. DESIGN:
      Auditory cortical evoked potentials were obtained from seven normal-hearing young
      adults in response to four naturally produced speech tokens (/bi/, /pi/,
      /[U0283]i/, and /si/). Stimuli were tokens from the standardized UCLA version of
      the Nonsense Syllable Test (NST) ( Dubno & Schaefer, 1992). Using a repeated
      measures design, subjects were tested and then retested within an 8-day period.
      RESULTS: Auditory cortical evoked potentials elicited by naturally produced
      speech sounds were reliably recorded in individuals. Also, naturally produced
      speech tokens, representing different acoustic cues, evoked distinct neural
      response patterns. CONCLUSIONS: 1) Cortical evoked potentials elicited by
      naturally produced speech sounds can be reliably recorded in individuals. 2)
      Naturally produced speech tokens, representing different acoustic cues, evoke
      distinct neural response patterns. 3) Given the reliability of the response, this
      work has potential application to the study of neural processing of speech in
      individuals with communication disorders as well as changes over time after
      various types of auditory rehabilitation.

PMID- 12799545
TI  - Evaluation of anti-hsp70 antibody screening in sudden deafness.
AB  - OBJECTIVE: To assess the diagnostic utility of anti-hsp70 antibody screening in
      sudden deafness. DESIGNS: era from 27 patients with sudden deafness and 100
      healthy blood donors were analyzed by Western blotting (WB) for the presence of
      antibodies against 68 kD heat shock protein (anti-hsp70). RESULTS: 19% of the
      patient sera and 14% of the control sera turned out positive, which was not
      significantly different. CONCLUSIONS: The anti-hsp70 WB test lacks clinical
      utility for diagnostic screening in patients with sudden deafness.

PMID- 12799547
TI  - Equivalent dipoles of the binaural interaction components and their comparison
      with binaurally evoked human auditory 40 Hz steady-state evoked potentials.
AB  - OBJECTIVE: The purpose of this study was to acquire the Binaural Interaction (BI)
      components of the auditory middle-latency steady-state 40 Hz potentials, compare
      them with those of the binaurally evoked 40 Hz response and with transient-evoked
      Auditory Middle Latency Evoked Potentials (AMEP) and suggest possible
      contributors and generators of the composite 40 Hz BI. METHODS: Potentials were
      recorded from 15 normal-hearing adults in response to 40/sec clicks. BI was
      derived by subtracting the binaurally evoked potentials from the algebraic sum of
      the evoked potentials to left and to right ear stimulation. Latencies, magnitudes
      and orientations of the dipole equivalents of 40 Hz components were compared with
      their BI counterparts, as estimated by three-channel Lissajous' trajectories.
      Comparison of the transient AMEP to binaural stimulation with the BI of the
      steady-state 40 Hz response was also conducted to elucidate the contributions of
      different levels along the auditory pathway to the 40 Hz BI responses. RESULTS:
      Each cycle of the BI of the steady-state 40 Hz AMEP included four components that
      corresponded in latency, amplitude, and dipole orientation to their counterparts
      in the binaurally evoked waveform. Amplitudes of BI components were 50 to 60% of
      the respective values in the binaurally evoked potentials. Orientations of BI
      components matched those of the cortical components in the transient-evoked AMEP.
      CONCLUSIONS: The results suggest that the main contribution to the 40 Hz BI is
      from rate resistant thalamo-cortical neurons. The results also suggest that the
      binaural cortical neurons contributing to the 40 Hz BI are less affected by
      increased rate than monaural neurons.

PMID- 12799546
TI  - Exploring the language and literacy outcomes of pediatric cochlear implant users.
AB  - OBJECTIVE: The principal goal of this study was to investigate the relationship
      between language and literacy (i.e., reading and writing) skills in pediatric
      cochlear implant users. A peripheral objective was to identify the children's
      skills that were in need of remediation and subsequently to provide suggestions
      for remedial programming. It was predicted that the robust language skills often
      associated with children who have cochlear implant experience would facilitate
      the development of literacy skills. It was further proposed that the language and
      literacy skills of pediatric cochlear implant users would approximate the
      language and literacy skills of children with normal hearing. DESIGN: Sixteen
      pediatric cochlear implant users' language and literacy skills were evaluated and
      then compared with a reference group of 16 age-matched, normal-hearing children.
      All 32 participants were educated in mainstream classes within the public school
      system in the Midwest. The "Sentence Formulation" and "Concepts and Directions"
      subtests of the Clinical Evaluation of Language Fundamentals-3 test were used to
      evaluate receptive and expressive language skills. Reading comprehension was
      evaluated with the "Paragraph Comprehension" subtest of the Woodcock Reading
      Mastery Test. Performance measures for the writing analyses included
      productivity, complexity and grammaticality measures. RESULTS: Children with
      cochlear implants performed within 1 SD of the normal-hearing, age-matched
      children on measures of language comprehension, reading comprehension and writing
      accuracy. However, the children with cochlear implants performed significantly
      poorer than the children with normal hearing on the expressive "Sentence
      Formulation" subtest. The cochlear implant users also produced fewer words on the
      written narrative task than did the normal-hearing children, although there was
      not a significant difference between groups with respect to total words per
      clause. Furthermore there was a strong correlation between language performance
      and reading performance, as well as language performance and total words produced
      on the written performance measure for the children using cochlear implants.
      CONCLUSIONS: The results of this study suggest that the language skills of
      pediatric cochlear implant users are related to and correlated with the
      development of literacy skills within these children. Consequently, the
      performance of the cochlear implant users, on various language and literacy
      measures, compared favorably to an age-matched group of children with normal
      hearing. There were significant differences in the ability of the cochlear
      implant users to correctly utilize grammatical structures such as conjunctions
      and correct verb forms when they were required to formulate written and oral
      sentences. Given this information, it would be appropriate for their educational
      or remedial language programs to emphasize the use and development of these
      structures.

PMID- 12799548
TI  - Activation of the signal transducer and activator of transcription 1 signaling
      pathway in thymocytes from HIV-1-infected human thymus.
AB  - OBJECTIVE: To identify HIV-induced host factors in the severe combined
      immunodeficient (SCID)-hu Thy/Liv mouse that may contribute to HIV pathogenesis
      in the thymus. DESIGN: To identify genes specifically altered by HIV-1 infection
      using the cDNA microarray assay, SCID-hu Thy/Liv organs derived from the same
      donors were used. Therefore, no genetic variations existed between HIV and mock
      infected samples. In addition, the 12-14 day post-infection timepoint was chosen
      because no significant thymocyte depletion was detected in HIV-infected Thy/Liv
      organs, so mRNA from the same cell types could be compared. METHODS: Using SCID
      hu Thy/Liv mice constructed from the same donor tissues, we analysed the
      expression of 9183 host genes in response to HIV infection with cDNA microarrays.
      Expression of selected genes with more than threefold induction was confirmed by
      measuring RNA (reverse transcriptase-polymerase chain reaction; RT-PCR) and
      proteins. RESULTS: HIV-1 (JD or NL4-3) infection of the SCID-hu Thy/Liv mouse led
      to more than threefold induction of 19 genes, 12 of which were IFN-inducible and
      six were unknown EST clones. We confirmed induction by RT-PCR and protein blots.
      Both signal transducer and activator of transcription (STAT)1 and STAT2 proteins
      were induced, and STAT1 was also activated by phosphorylation at the Tyr701 and
      Ser727 sites in human thymus infected with HIV-JD or NL4-3. Treatment of human
      fetal thymus organ culture or human thymocytes with recombinant HIV-1 gp120
      proteins also led to induction or activation of STAT1. CONCLUSION: HIV-1
      infection of the thymus led to activation of the STAT1 signaling pathway in
      thymocytes, which may contribute to HIV-1 pathogenesis in the thymus.

PMID- 12799549
TI  - The chemokine receptor CX3CR1 controls homing and anti-viral potencies of CD8
      effector-memory T lymphocytes in HIV-infected patients.
AB  - OBJECTIVES: We have recently reported that the polymorphism of the fractalkine
      receptor, CX3CR1, provides a new marker for prognosis in HIV disease. In order to
      understand the mechanism by which CX3CR1 participates in the regulation of HIV
      immune responses, we investigated its expression and role on T lymphocytes in HIV
      infected patients. DESIGN: For that purpose, we analysed the expression of CX3CR1
      on CD4 and CD8 effector-memory subsets in HIV-positive individuals by flow
      cytometric analyses, and studied its potential role in the migration and function
      of CD8 effector cells. RESULTS: We observed an increased frequency of CD8 cells
      expressing CX3CR1 that was correlated with disease progression in HIV-infected
      patients compared with normal individuals. CX3CR1+ was expressed mainly on
      activated and differentiated CCR7-CD45RA-negative memory lymphocytes.
      Interestingly, CX3CR1 appeared as the main homing receptor of these cells that
      have downmodulated most other chemokine receptors. The CD8+CX3CR1+ lymphocytes
      were engaged in the cytotoxic lineage (perforin+, CD27-negative and CD57+). Ex
      vivo analysis showed that CX3C ligand-1 inhibits IFNgamma production in response
      to T cell receptor engagement. CONCLUSION: CX3CR1 and its ligand could contribute
      to the specific migratory pattern of late-stage differentiated CD8 cells and
      participate in the regulation of effector function of CD8 lymphocytes during HIV
      infection.

PMID- 12799550
TI  - Structural defects and variations in the HIV-1 nef gene from rapid, slow and non
      progressor children.
AB  - OBJECTIVES: Evaluation of sequence evolution as well as structural defects and
      mutations of the human immunodeficiency virus-type 1 (HIV-1) nef gene in relation
      to disease progression in infected children. DESIGN: We examined a large number
      of nef alleles sequentially derived from perinatally HIV-1-infected children with
      different rates of disease progression: six non-progressors (NPs), four rapid
      progressors (RPs), and three slow progressors (SPs). METHODS: Nef alleles (182
      total) were isolated from patients' peripheral blood mononuclear cells (PBMCs),
      sequenced and analysed for their evolutionary pattern, frequency of mutations and
      occurrence of amino acid variations associated with different stages of disease.
      RESULTS: The evolution rate of the nef gene apparently correlated with CD4+
      decline in all progression groups. Evidence for rapid viral turnover and positive
      selection for changes were found only in two SPs and two RPs respectively. In
      NPs, a higher proportion of disrupted sequences and mutations at various
      functional motifs were observed. Furthermore, NP-derived Nef proteins were often
      changed at residues localized in the folded core domain at cytotoxic T
      lymphocytes (CTL) epitopes (E(105), K(106), E(110), Y(132), K(164), and R(200)),
      while other residues outside the core domain are more often changed in RPs
      (A(43)) and SPs (N(173) and Y(214)). CONCLUSIONS: Our results suggest a link
      between nef gene functions and the progression rate in HIV-1-infected children.
      Moreover, non-progressor-associated variations in the core domain of Nef,
      together with the genetic analysis, suggest that nef gene evolution is shaped by
      an effective immune system in these patients.

PMID- 12799552
TI  - Total lymphocyte count and hemoglobin combined in an algorithm to initiate the
      use of highly active antiretroviral therapy in resource-limited settings.
AB  - OBJECTIVE: To develop clinical algorithms that improve the sensitivity of
      surrogate markers to initiate the use of highly active antiretroviral therapy
      (HAART) in resource-limited settings. DESIGN: A retrospective evaluation of total
      lymphocyte counts (TLC) and hemoglobin to predict the CD4 lymphocyte count.
      METHODS: A total of 3269 members of the Johns Hopkins HIV observational cohort
      contributed 22 690 paired observations of CD4 lymphocyte counts and TLC. Two
      methods were used to evaluate the effect of combining TLC and hemoglobin to
      predict CD4 cell counts below 200 cells/mm3 before the initiation of HAART in
      1451 participants; 55.3% of participants had CD4 cell counts below 200 cells/mm3.
      RESULTS: TLC below 1200 cells/mm3 and hemoglobin below 12 g/dl significantly
      predicted CD4 cell counts below 200 cells/mm3. For TLC alone sensitivity was
      70.7% and specificity was 81.7%. For both men and women, we chose a TLC lower
      cutoff point of 1200 cells/mm3, an upper cutoff point of 2000 cells/mm3, and
      hemoglobin of 12 g/dl. For men, method I generated sensitivity of 78.0% and
      specificity of 77.5%. Method II improved specificity to 81.8%. For women, method
      I increased sensitivity to 85.6% and decreased specificity to 64.1%. Method II
      improved specificity to 81.4%. CONCLUSION: TLC below 1200 cells/mm3 were
      associated with CD4 cell counts below 200 cells/mm3 as in the WHO guidelines, but
      sensitivity was low. Adding hemoglobin to TLC increased sensitivity, thereby
      reducing the risk of false-negative results. Our model may serve as a template
      for the development of algorithms to initiate the use of HAART in resource
      limited settings.

PMID- 12799551
TI  - Suppression of leukemia inhibitor factor in lymphoid tissue in primary HIV
      infection: absence of HIV replication in gp130-positive cells.
AB  - BACKGROUND: Leukemia inhibitor factor (LIF), a member of the interleukin-6
      cytokine family, has recently been shown to inhibit HIV-1 replication both in
      vivo and in vitro. OBJECTIVE: LIF and its corresponding receptors gp130 and LIF
      receptor-alpha (LIFR-alpha) were studied in lymphoid tissue (LT) to reveal
      potential systemic immunoregulatory effects during the course of HIV-1 infection.
      METHODS: LIF, gp130, LIFR-alpha and HIV-1 replicating cells were identified at
      the single cell level by immunohistochemistry and quantified by computerized in
      situ imaging in tonsil and lymph nodes biopsies (LT) from patients with primary
      HIV-1 infection (PHI), chronic HIV-1 infection (cHI), long-term non-progressors
      (LTNP) and HIV-1 seronegative controls. RESULTS: LIF and its receptors, gp130 and
      LIFR-alpha were significantly (P < 0.005) upregulated in LT from PHI patients as
      compared with HIV-1 seronegative controls. Expression of LIF in cHI was
      comparable to LIF levels in HIV-1 seronegative controls whereas LTNP showed
      significantly reduced LIF expression (P < 0.05). LIF receptors, gp130 and LIFR
      alpha were significantly upregulated in cHI (P < 0.005) but downregulated in LTNP
      (P < 0.05 and P < 0.005, respectively). LIF expressing cells could be
      demonstrated in LT 2 days after onset of acute retroviral syndrome. LIF
      expression was evident in CD3, CD4 and CD8 cells. Furthermore, high plasma viral
      load was associated with high expression of LIF in LT. Finally, no HIV-1
      replication could be found in CD4 gp130-positive cells in PHI. CONCLUSIONS: LIF,
      gp130 and LIFR-alpha showed increased expression in LT from patients with PHI.
      Furthermore, HIV-1 replication did not occur in cells expressing the LIF
      signaling receptor, gp130, indicating that LIF may be associated with control of
      HIV-1 replicating cells in vivo.

PMID- 12799553
TI  - Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in
      protease inhibitor-treated and naive HIV-infected children.
AB  - OBJECTIVE: To determine the extent and degree of abnormalities of serum lipids,
      glucose homeostasis and abdominal adipose tissue distribution in protease
      inhibitor (PI)-treated and PI-naive HIV-infected children. DESIGN: A cross
      sectional study involving HIV-infected children, 3-18 years of age, in a
      paediatric tertiary care centre. MAIN OUTCOME MEASURES: Total, HDL and LDL
      cholesterol, triglycerides, glucose, insulin, proinsulin and C-peptide were
      determined in the fasting state. Insulin resistance was assessed using the
      homeostatic model assessment-insulin resistance (HOMA-IR). Abdominal adipose
      tissue distribution was determined by single-slice computed tomography at the
      umbilical level. RESULTS: Thirty PI-treated and 20 PI-naive children were
      evaluated (76% prepubertal). PI-treated children had significantly higher total
      cholesterol (P = 0.0021), LDL-cholesterol (P = 0.019) and triglycerides (P =
      0.0018). Serum glucose, insulin, proinsulin and C-peptide, the insulin : glucose
      ratio, HOMA-IR and abdominal adipose tissue distribution were similar in the two
      groups. Clinical and immunological HIV categories, viral load, CD4 cell count and
      stavudine therapy were not significantly associated with serum lipids, insulin
      resistance or abdominal adipose tissue distribution. The predictor variable most
      strongly associated with fasting serum insulin and HOMA-IR was the Tanner stage.
      Age was the most significant predictor variable of the visceral : subcutaneous
      adipose tissue ratio. CONCLUSION: In this cohort of predominantly prepubertal HIV
      infected children, PI therapy was associated with an atherogenic dyslipidemia but
      not with insulin resistance or abnormal abdominal adipose tissue distribution.
      The results suggest that children, particularly prepubertal children, are less
      susceptible than adults to PI-induced changes in glucose homeostasis and
      abdominal adipose tissue distribution.

PMID- 12799554
TI  - Mitochondrial DNA depletion and morphologic changes in adipocytes associated with
      nucleoside reverse transcriptase inhibitor therapy.
AB  - BACKGROUND: Nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy
      provides sufficient conditions for progressive subcutaneous fat wasting in HIV
      infected patients. As NRTI-induced host toxicity is proposed to involve cellular
      mitochondrial DNA (mtDNA) depletion, determinants of cellular mtDNA copy number
      and mitochondrial mass in adipocyte samples from NRTI-treated HIV-infected
      patients and antiretroviral-naive controls were investigated. Adipose tissue
      morphology was also assessed. METHODS: Subcutaneous fat samples were obtained
      from NRTI-treated, HIV-infected patients (n = 21), antiretroviral therapy-naive
      HIV-infected controls (n = 11), and HIV-seronegative controls (n = 6). Non
      adipocytes were removed by collagenase digestion. Adipocyte mtDNA copies/cell was
      measured using a real time PCR-based assay, and adipocyte mitochondrial protein
      content was also measured. Light and electron microscopy were performed on tissue
      samples. FINDINGS: Adipocyte mtDNA copies/cell values were similar (P = 0.56) in
      HIV seronegative and HIV-infected control groups. NRTI treatment was associated
      with reduced adipocyte mtDNA copies/cell, representing mean mtDNA depletion in
      NRTI-treated individuals of 77.7% compared with the mean value for the HIV
      infected control group (P < 0001). Additionally, significant differences were
      found in adipocyte mtDNA copies/cell between patients receiving stavudine (n =
      12, mean mtDNA depletion 87.1%) and zidovudine (n = 9, mean mtDNA depletion
      52.1%) (P < 0.001). Adipocyte mitochondrial mass was increased in the stavudine
      group only (mean increase 289%, P < 0.01). INTERPRETATION: NRTI therapy is
      associated with mtDNA depletion and mitochondrial proliferation in adipocytes,
      consistent with the hypothesis that NRTI-induced mtDNA depletion contributes to
      the pathogenesis of subcutaneous fat wasting. Morphologic assessment also
      supports a role for NRTI therapy in inducing adipocyte metabolic dysfunction and
      cell death.

PMID- 12799555
TI  - Therapy with atazanavir plus saquinavir in patients failing highly active
      antiretroviral therapy: a randomized comparative pilot trial.
AB  - OBJECTIVES: To assess the safety, efficacy of atazanavir (400 and 600
      mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir (400 mg/400 mg)
      twice daily with two nucleoside reverse transcriptase inhibitors (NRTIs) in
      highly active antiretroviral therapy failure. DESIGN AND METHODS: Randomized,
      multinational, 48-week, pilot trial with antiretroviral-experienced patients
      having at least 1000 HIV-1 RNA copies/ml, 100 x 106 CD4 cells/l (75 x 106 cells/l
      without AIDS diagnosis) and virological response to a prior regimen. Efficacy was
      evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks. RESULTS:
      Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44,
      1.19 and 1.66 log(10) copies/ml (P = NS) and comparable virological response (>
      1.0 log(10) decrease HIV-1 RNA or HIV-1 RNA < 400 copies/ml) was achieved in 41,
      29 and 35% (P = NS); and mean CD4 cell increases, 109, 55 and 149 x 106 cells/l
      in atazanavir 400-mg, atazanavir 600-mg and ritonavir groups, respectively. There
      were fewer adverse event discontinuations in the atazanavir groups (9%, 11%)
      versus the ritonavir group (30%) and atazanavir lacked adverse effects on lipids.
      In the atazanavir 400-mg, atazanavir 600-mg and ritonavir groups the mean changes
      from baseline at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol
      concentrations were -0.6, -6.7 and 23.2%, respectively and in fasting
      triglyceride concentrations they were -4.8, -27.1 and 93.0%, respectively (P <
      0.05, LDL cholesterol; P < 0.001, fasting triglyceride; atazanavir/saquinavir
      versus ritonavir/saquinavir). CONCLUSIONS: In antiretroviral-experienced
      patients, once-daily atazanavir/saquinavir was safe and well tolerated, showing
      comparable efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs.
      Small lipid changes from baseline with atazanavir/saquinavir were not clinically
      significant in comparison with the prompt, marked and sustained changes of a
      magnitude suggesting clinical relevance achieved in the ritonavir/saquinavir
      group.

PMID- 12799556
TI  - Kinetics of disappearance of resistance mutations and reappearance of wild-type
      during structured treatment interruptions.
AB  - OBJECTIVE: To monitor the disappearance of resistance-associated mutations and
      reappearance of wild-type (WT) virus during structured treatment interruptions
      (STI) using DNA sequencing and line probe assay. METHODS: Eleven HIV-1-infected
      patients participating in the MUTAVIR study undergoing a 3-month STI after multi
      HAART failure were monitored biweekly. Genotypes were assessed by sequencing and
      VERSANT HIV-1 Resistance Assays (LiPA). RESULTS: At treatment interruption, 54
      mutations in total were identified with both methods among the patients. LiPA
      provided a result for 93.3% of the codons at baseline. For 37 mutations, a
      complete reversion of mutant to WT was observed with one of the two methods.
      Among these, LiPA detected mutations in 23 codons for 7 to 52 days longer, in 10
      codons for the same period, and in four codons for a shorter time than
      sequencing. Similarly, LiPA detected 35 WT codons 8 to 86 days earlier, and 15 at
      the same time point as sequencing. A sharp reduction in the number of mutations
      was observed at the time of viral load increase in five of the 11 patients.
      Taking only the codons detected by LiPA into consideration, two patients showed a
      complete reversion to WT according to both genotyping assays at the end of the
      STI period. CONCLUSIONS: The determination of the timepoint at which a virus
      population of an HIV-1 patient undergoing STI reverts to WT is dependent on the
      assay used. The viral load increase in most patients is compatible with the
      outgrowth of virus with fewer or no mutations.

PMID- 12799557
TI  - The association between hepatitis C virus and HIV-1 in preparatory cohorts for
      HIV vaccine trials in Thailand.
AB  - OBJECTIVES: To study the association between hepatitis C virus (HCV) and HIV-1,
      and HCV seropositivity as an indicator of HIV-1 risk behavior for HIV vaccine
      preparatory cohorts in Thailand. DESIGN: Cross-sectional study of HIV-1-infected
      persons identified at screening for potential HIV vaccine trial cohort studies.
      METHODS: Sera from HIV-1-infected and uninfected volunteers was matched by age,
      sex, and community, and tested for HCV reactivity. Logistic regression methods
      were used to measure associations between HIV-1, HCV and other risk factors for
      HIV infection. RESULTS: The prevalence of HCV among HIV-negative controls was
      8.3% (6/72) for men and 4.2% (5/118) for women. Co-infection with HIV and
      occurred in 50.7% (37/73) of men and 3.4% (4/118) of women. Among men who
      reported injection drug use (IDU), 96.4% (27/28) were HCV seropositive. No women
      reported IDU. HCV was associated with HIV infection [odds ratio (OR), 11.3; 95%
      confidence interval (CI), 4.4-29.3] and IDU (OR, 12.0; 95% CI, 3.4-41.9) among
      men, but not women (OR, 0.8; 95% CI, 0.2-3.0). After adjustment for potential
      confounding, HCV, but not IDU, remained strongly associated with HIV-1 infection
      among men (OR, 9.4; 95% CI, 2.7-32.6). CONCLUSIONS: The strong associations
      between HCV seropositivity, HIV-1 infection, and IDU history suggest that IDU was
      reported accurately in this study. The surprisingly high prevalence of HCV among
      HIV-1-infected young men may assist health policy makers in the choice of
      behavioral interventions for this important subgroup of the population.

PMID- 12799558
TI  - Adherence is not a barrier to successful antiretroviral therapy in South Africa.
AB  - OBJECTIVE: To determine adherence of an indigent African HIV-infected cohort
      initiating antiretroviral therapy (ART); to identify predictors of incomplete
      adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml). DESIGN:
      Prospective monitoring of adherence in a poor HIV-positive cohort, attending a
      public sector hospital and receiving ART through phase III studies. METHODS:
      Adherence to ART was determined over 48 weeks by counting tablet-returns.
      Logistic regression models including age, WHO HIV stage, home language, socio
      economic status, complexity and type of regimen were fitted to determine
      predictors of incomplete adherence and virologic failure at 48 weeks. RESULTS:
      289 patients were recruited between January 1996 and May 2001. Median (mean)
      adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio
      (RR), 3.07; 95% confidence interval (CI), 1.40-6.74], speaking English (RR, 0.41;
      95% CI, 0.21-0.80) and age (RR, 0.97; 95% CI, 0.94-0.99) were independent
      predictors of incomplete adherence. Socio-economic status, sex and HIV stage did
      not predict adherence. Independent predictors of virologic failure included
      baseline viral load (RR, 2.57; 95% CI, 1.57-4.22) and three times daily dosing
      (RR, 2.64; 95% CI, 1.23-5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10
      3.57), age (RR, 0.96; 95% CI, 0.92-0.99) and dual nucleoside therapy (RR, 2.69;
      95% CI, 1.17-6.15). CONCLUSION: The proportion of individuals achieving viral
      suppression matched results from the developing world. Speaking the same language
      as site staff and simplified dosing frequency were beneficial. Socio-economic
      status had no impact on adherence and should not be used as a limitation to ART
      access.

PMID- 12799560
TI  - Doubts about DOT: antiretroviral therapy for resource-poor countries.
AB  - INTRODUCTION: Directly observed therapy programs developed for tuberculosis (TB)
      have been suggested as a model for the provision of HIV medications in resource
      poor countries in order to ensure adherence and prevent drug resistance. METHODS:
      Opinions were formed based on a review of scientific literature regarding the
      effectiveness of witnessed dosing in directly observed TB therapy programs,
      adherence to HIV antiretroviral therapy in resource-rich and resource-poor
      settings, relationship between adherence and HIV antiretroviral drug resistance,
      HIV viral load and risk of HIV transmission, and stigmatization concerns related
      to HIV and TB in resource-poor settings. RESULTS/CONCLUSIONS: We suggest that the
      enthusiasm for HIV directly observed therapy programs is premature based on:
      equivocal evidence that witnessed dosing is superior to self administered
      therapy; mistaken assumptions that resource-poor countries are a 'special case'
      with respect to adherence; possible paradoxical impact of good adherence on HIV
      drug resistance; unproven efficacy of antiretroviral therapy in preventing HIV
      transmission; and potential stigmatization of daily antiretroviral dosing.

PMID- 12799559
TI  - Prevention of mother-to-child transmission of HIV in Africa: successes and
      challenges in scaling-up a nevirapine-based program in Lusaka, Zambia.
AB  - BACKGROUND: Nearly half of perinatal HIV infection is preventable with nevirapine
      (NVP), which has transformed the ability to confront this transmission route in
      resource-limited settings. METHODS: A NVP-based perinatal HIV prevention program
      initiated in Lusaka, Zambia in November 2001. RESULTS: The first 12 months cost
      US$221 000 and enabled 178 district health employees to be trained in voluntary
      counseling and testing: 17 263 pregnant women were counseled for HIV, 12 438
      (72%) were tested, and 2924 (24%) were found to be infected with HIV. NVP has
      been taken by 1654 (57%) mothers and 1157 (40%) babies. It is estimated that at
      least 190 infants have been spared HIV infection (11 per 1000 counseled women or
      65 per 1000 identified HIV-infected women). CONCLUSIONS: Prevention of mother-to
      child HIV transmission is feasible and cost effective in resource-limited
      settings. In Lusaka, thousands of women have received voluntary counseling and
      testing and NVP therapy under the present scheme. Patient attrition and non
      adherence represented a major source of program inefficiency, which requires to
      be systematically addressed.

PMID- 12799561
TI  - HIV inhibitory activity generated by antigen-stimulated cord blood leukocytes.

PMID- 12799562
TI  - No significant enhancement of protection by Tat-expressing Sendai viral vector
      booster in a macaque AIDS model.

PMID- 12799563
TI  - No influence of human herpesvirus 8 infection on the progression of HIV-1
      infection in initially asymptomatic patients.

PMID- 12799564
TI  - Haemophilus influenzae type b conjugate vaccine-induced immunological memory in
      symptomatic HIV-1-infected children.

PMID- 12799565
TI  - Tuberculosis active case-finding in a mother-to-child HIV transmission prevention
      programme in Soweto, South Africa.

PMID- 12799567
TI  - HIV risk among a sample of drug using male sex workers.

PMID- 12799566
TI  - Low prevalence of hepatitis C virus antibodies in HIV-endemic area of Zimbabwe
      support sexual transmission as the major route of HIV transmission in Africa.

PMID- 12799568
TI  - Zoonotic diseases and at-risk patients: a survey of veterinarians and physicians.

PMID- 12799569
TI  - Sustained high levels of serum HHV-8 DNA years before multicentric Castleman's
      disease despite full suppression of HIV with highly active antiretroviral
      therapy.

PMID- 12799570
TI  - Prolonged remission of HIV-associated multicentric Castelman's disease with an
      anti-CD20 monoclonal antibody as primary therapy.

PMID- 12799571
TI  - Late cerebral relapse of a Mycobacterium avium complex disseminated infection in
      an HIV-infected patient after cessation of antiretroviral therapy.

PMID- 12799572
TI  - Plasma IL-6 as a marker of mycobacterial immune restoration disease in HIV-1
      infection.

PMID- 12799573
TI  - Hypersusceptibility to non-nucleoside reverse transcriptase inhibitors in HIV-1.

PMID- 12799574
TI  - Modifying dietary fat intake can reduce serum cholesterol in HIV-associated
      hypercholesterolemia.

PMID- 12799575
TI  - Bone dysmetabolism in HIV infection: a melting pot of opinions.

PMID- 12799576
TI  - Electronic monitoring of adherence to highly active antiretroviral therapy
      changes medication-taking behaviour?

PMID- 12799577
TI  - Latrogenic nephrogenic diabetes insipidus.

PMID- 12799578
TI  - Backing nurses pays big dividends.

PMID- 12799579
TI  - Bringing depression out of the shadows.

PMID- 12799587
TI  - How good a Samaritan should you be?

PMID- 12799585
TI  - What you need to know about the smallpox vaccine.

PMID- 12799586
TI  - Molly had a most complicated pregnancy.

PMID- 12799588
TI  - Continuous renal replacement therapy: slow but steady.

PMID- 12799589
TI  - Pump up your knowledge of insulin pumps.

PMID- 12799590
TI  - Patient-education guide: latex allergy.

PMID- 12799591
TI  - Using pain to assess neurologic response.

PMID- 12799592
TI  - Getting a fix on orthopedic care.

PMID- 12799593
TI  - Lightning strike.

PMID- 12799594
TI  - Discrimination of dementia with lewy bodies from Alzheimer disease and Parkinson
      disease using the clock drawing test.
AB  - OBJECTIVE: The authors' objective was to examine the ability of the Clock Drawing
      Test to discriminate Dementia with Lewy bodies from Alzheimer disease and
      Parkinson disease. BACKGROUND: Recent advances in medical treatments for dementia
      underscore the importance of differentiating among dementia subtypes. Clinically,
      Dementia with Lewy bodies can often be difficult to discriminate from Alzheimer
      disease and Parkinson disease because of similar and overlapping cognitive and
      motor features. While the Clock Drawing Test has been shown to discriminate
      dementia from normal aging fairly accurately, less is known about its ability to
      discriminate between various dementia groups. METHODS: Patients with Alzheimer
      disease (n = 22), patients with cognitively impaired Parkinson disease (n = 17),
      and patients with Dementia with Lewy bodies (n = 20), matched for age, education,
      and dementia severity, were compared on the Clock Drawing Test, scored for
      overall accuracy as well as the presence of specific error types. RESULTS: There
      were no significant group differences on a global quantitative measure of Clock
      Drawing Test performance. With regard to differences on the error types
      evaluated, the patients with Dementia with Lewy bodies were more likely to make
      conceptual errors than the patients with Alzheimer disease and Parkinson disease,
      and the patients with Parkinson disease and Dementia with Lewy bodies made more
      planning errors than the patients with Alzheimer disease. Classification accuracy
      was fair, with 69% overall classification for Alzheimer disease versus Dementia
      with Lewy bodies, and 68% overall classification for Parkinson disease versus
      Dementia with Lewy bodies. CONCLUSIONS: Although some differences may exist in
      the qualitative features of clock drawing performance between these patient
      groups, overall clock drawing performance is relatively similar, and as a single
      instrument, the Clock Drawing Test provides limited discrimination of Dementia
      with Lewy bodies from Alzheimer disease and Parkinson disease.

PMID- 12799595
TI  - Odor identification deficits in diffuse lewy body disease.
AB  - OBJECTIVES: To describe odor identification performance in patients with diffuse
      Lewy body disease and determine the clinical utility of odor identification tests
      in distinguishing diffuse Lewy body disease from Alzheimer disease. BACKGROUND:
      The presence of olfactory deficits, especially odor identification deficits, has
      been well established in both Alzheimer disease and Parkinson disease. The
      presence of olfactory deficits in diffuse Lewy body disease is also likely given
      the overlap of clinical symptoms and neuropathology with Alzheimer disease and
      Parkinson disease. However, odor identification abilities have not been described
      previously in diffuse Lewy body disease. METHODS: Nine patients from a clinic
      sample with diffuse Lewy body disease and nine carefully matched patients with
      Alzheimer disease were administered an odor identification task as part of their
      neuropsychologic evaluations. RESULTS: Patients with diffuse Lewy body disease
      performed significantly worse than patients with Alzheimer disease on the odor
      identification test. CONCLUSIONS: Odor identification deficits may be more
      prevalent and severe in people with diffuse Lewy body disease than in people with
      Alzheimer disease, and olfactory testing may be useful in antemortem differential
      diagnosis of the two disorders.

PMID- 12799596
TI  - Executive and nonexecutive neuropsychological functioning in antisocial
      personality disorder.
AB  - OBJECTIVE: To examine the relationships between antisocial personality disorder
      and executive abilities as well as antisocial personality disorder with other
      domains of cognitive functioning. BACKGROUND: Previous research has suggested
      that antisocial personality disorder is associated with impaired executive
      functioning. However, methodological limitations of past research have resulted
      in inconsistent findings. METHODS: Executive functioning and other cognitive
      abilities were compared in four demographically matched groups of middle-aged
      community dwelling male veterans (N = 336). The groups were: (A). those with
      active antisocial personality disorder psychopathology; (B). those with a
      lifetime prevalence of antisocial personality disorder but inactive antisocial
      personality disorder psychopathology; (C). a nonantisocial personality disorder
      psychiatrically matched control group; and (D). a normal control group. RESULTS:
      Multivariate analysis of variance revealed that the four groups were not
      statistically significantly different on measures of executive functioning or
      other cognitive abilities. CONCLUSIONS: Those with antisocial personality
      disorder perform at comparable levels to psychiatric and normal controls with
      respect to executive functioning and other domains of cognitive ability (i.e.,
      language, memory, visuospatial, and motor abilities). An incidental finding was
      that, over time, the antisocial personality disorder groups improved more than
      control groups on a measure of general intellectual aptitude.

PMID- 12799597
TI  - A three-factor model of cognition in Alzheimer disease.
AB  - OBJECTIVE: To use principal factors analysis to model cognition in Alzheimer
      disease. BACKGROUND: Earlier studies have used factor analysis to examine the
      effects on Alzheimer disease cognition of either heterogeneity in premorbid
      cognition or heterogeneity in the disease process itself. In the current study,
      both sources of heterogeneity were incorporated within a single model. METHODS:
      Two hundred sixty-one patients with probable Alzheimer disease (92 White Non
      Hispanic, 148 Hispanic, and 21 African-American) were tested with the Mini-Mental
      Status Examination, the Assessment of Cognitive Abilities in Dementia, and the
      Short Portable Mental Status Examination. RESULTS: Three factors were obtained:
      one with loadings for memory and orientation, a second with loadings for language
      and praxis, and a third with loadings for executive functions. Factors 1 and 2
      declined over 1.82 years (p = 0.0002, p = 0.0001); Factor 3 scores remained
      invariant over this period (p = 0.16). Furthermore, only Factor 3 scores
      correlated with either education (p = 0.0001) or ethnicity (p = 0.0001).
      CONCLUSIONS: A possible interpretation is that Factors 1 and 2 may reflect two
      components of the Alzheimer disease process while Factor 3 may provide an
      estimate of premorbid cognition. A potential practical application of the
      analysis is that it may provide a measure of Alzheimer disease decline that is
      free from correlation with education or ethnicity.

PMID- 12799598
TI  - Relative effects of repetitive transcranial magnetic stimulation and
      electroconvulsive therapy on mood and memory: a neurocognitive risk-benefit
      analysis.
AB  - OBJECTIVE: Two procedures for treating major depressive disorder were compared
      with regard to their respective effects on mood and cognition. BACKGROUND:
      Fourteen patients underwent treatment with electroconvulsive therapy and 14
      underwent treatment with repetitive transcranial magnetic stimulation. Patients
      were tested on three occasions: before initiation of treatment, at the end of
      treatment, and 2 weeks after the end of treatment. METHODS: Electroconvulsive
      therapy was applied unilaterally approximately three times per week for 2 to 4
      weeks. Repetitive transcranial magnetic stimulation was applied in sessions of
      1600 stimuli at 10 Hertz and 90% of motor threshold intensity to the left
      dorsolateral prefrontal cortex daily (Monday through Friday) for 2 consecutive
      weeks. RESULTS: Results indicate that electroconvulsive therapy had a more
      positive effect on mood than did a 2-week trial of repetitive transcranial
      magnetic stimulation. With regard to cognitive outcome measures,
      electroconvulsive therapy exerted a deleterious but transient effect on various
      components of memory that were no longer detected 2 weeks after the end of
      treatment; however, there was evidence of persistent retrograde amnesia after
      treatment with electroconvulsive therapy. As a group, repetitive transcranial
      magnetic stimulation patients experienced only a modest reduction in depression
      severity but there was no evidence of anterograde or retrograde memory deficits
      in the aftermath of treatment with repetitive transcranial magnetic stimulation.
      CONCLUSIONS: Findings suggest that electroconvulsive therapy is associated with
      transient negative cognitive side effects, most of which dissipate in the days
      after treatment. Deficits of this sort are not apparent after treatment with a 2
      week course of repetitive transcranial magnetic stimulation.

PMID- 12799599
TI  - Prefrontal cortex transcranial magnetic stimulation does not change local
      diffusion: a magnetic resonance imaging study in patients with depression.
AB  - OBJECTIVE: To determine whether transcranial magnetic stimulation over the left
      dorsolateral prefrontal cortex produces pathologic changes or leakage of the
      blood-brain barrier in patients with depression by using apparent diffusion
      coefficient magnetic resonance imaging. BACKGROUND: Transcranial magnetic
      stimulation is a new technology for noninvasively stimulating the brain. It
      appears to be a relatively safe technique, with some important exceptions. Its
      neurobiologic mechanisms of action are poorly understood. One theory to explain
      its apparent antidepressant effects involves a potential change in local blood
      brain barrier settings, allowing passage of peripheral substances directly into
      brain parenchyma. Knowing whether transcranial magnetic stimulation changes local
      brain diffusion is important as well from a safety perspective. To test whether
      transcranial magnetic stimulation changes local brain diffusion, we used apparent
      diffusion coefficient magnetic resonance imaging in depressed patients undergoing
      interleaved transcranial magnetic stimulation/functional magnetic resonance
      imaging over the left prefrontal cortex. METHODS: Within a 1.5 Tesla magnetic
      resonance imaging scanner, 14 depressed patients were stimulated with a figure
      eight transcranial magnetic stimulation coil over the left prefrontal cortex.
      Apparent diffusion coefficient magnetic resonance imaging was acquired before,
      and immediately after, 1 Hertz transcranial magnetic stimulation (147 stimuli)
      intermittently delivered at a motor threshold of more than 7.35 minutes. Phase
      maps of the transcranial magnetic stimulation magnetic fields were used to guide
      region-of-interest placement. RESULTS: No significant qualitative apparent
      diffusion coefficient differences were observed before and after 1 Hertz
      transcranial magnetic stimulation underneath the coil. CONCLUSIONS: One Hertz
      transcranial magnetic stimulation over the left dorsolateral prefrontal cortex as
      applied in this study did not result in pathologic changes or leakage of the
      blood-brain barrier in patients with depression. If prefrontal transcranial
      magnetic stimulation at these usage parameters changes local diffusion, it is not
      an obvious or large effect.

PMID- 12799600
TI  - A review of research on natural support interventions in the workplace for people
      with disabilities.
AB  - Natural supports for workers with disabilities involve using co-workers,
      supervisors and other supports intrinsic to the job setting to facilitate job
      skill acquisition, maintenance and integration. The purpose of this article is to
      review the empirical literature related to natural supports in the workplace for
      increasing integration and to offer guidelines for implementation. The sources
      used are case studies and empirical research. Conclusions are offered in terms of
      limitations of current research, needs for future research and the changing roles
      of supported employment services.

PMID- 12799601
TI  - The 'smallest real difference' as a measure of sensitivity to change: a critical
      analysis.
AB  - If assessment instruments are used to measure efficacy or effectiveness, for
      example of rehabilitation programmes, they have to be sensitive (or responsive)
      to change. However, up to now there has been no consensus on what coefficient
      should be used for this end. Various effect sizes and criterion measures are
      widely acknowledged; tests of inferential statistics are also still used. The
      different coefficients may well provide different rank ordering of competitive
      instruments. Recently, the so-called 'smallest real difference' (SRD) was
      proposed as a measure of sensitivity to change. In the original formulation, the
      SRD was defined as the 95% confidence limit of the standard error of measurement
      (SEM) of the difference scores. Conceptually this is equivalent to what is known
      as the 'reliable change index' in psychotherapy research. The absolute values of
      the SEM/SRD indicate measurement error. In our view, this is merely complementary
      to the reliability concept and not a measure of sensitivity to change. Instead,
      we suggest using the percentage of patients reaching the SRD criterion to compare
      the sensitivity to change of competitive instruments. In contrast to other
      sensitivity-to-change indices, such an approach takes the different reliabilities
      of competitive assessment instruments explicitly into account.

PMID- 12799602
TI  - Chedoke-McMaster stroke assessment and modified Barthel Index self-assessment in
      patients with vascular brain damage.
AB  - With the conception of interdisciplinary and joint rehabilitation, and the
      adherence to impairment, activity and participation as rehabilitation goals, a
      comparison of assessment instruments that use different perspectives
      (professional, lay person, patient) and are employed by different professional
      groups addressing different issues such as in occupational therapy and in
      physical therapy, is required. The clinical admission-discharge assessment of the
      Chedoke-McMaster stroke assessment and the Barthel index data of 127 vascular
      brain-damaged patients, including patients with other neurological disorders,
      were compared. The German language version of these instruments proved highly
      reliable; the factorial structure indicated, with a few exceptions, the
      conceptualized dimensions and the Barthel index contributed to this structure
      with an additional dimension of drinking and eating as well as a continence
      factor. It takes eight items of the Barthel index to predict a substantial part
      of the total variance of the 15-item Chedoke-McMaster stroke assessment (r2=76),
      but only three Chedoke-McMaster items to predict the Barthel index total (r2=77).
      It is suggested that although further analyses of all instruments used in a
      rehabilitation centre are required, addressing their relationship to each other
      and their usefulness as admission-discharge measures, a rehabilitation
      conceptualization should proceed closely linked with the optimization of the
      assessment measures, thus providing a lean but comprehensive monitoring system.

PMID- 12799603
TI  - The influence of pain and pain-related fear and disability beliefs on walking
      velocity in chronic low back pain.
AB  - The purpose of this study was to examine the influence of anticipation of pain,
      sensory perception of pain and pain-related fear and disability beliefs on the
      gait characteristics of patients with chronic low back pain (CLBP). Thirty-one
      individuals with CLBP (16 men and 15 women) and 24 healthy individuals (11 men
      and 13 women) between 20 to 56 years of age participated in this study.
      Anticipated pain and the pain actually felt were measured with two separate
      visual analogue scales before and after preferred and fast walking performances.
      Pain-related fear and disability beliefs were measured with the Fear-Avoidance
      Belief Questionnaire (FABQ) and the Disability Belief Questionnaire (DBQ).
      Spatial and temporal walking parameters were measured at preferred and fast
      walking performances using a computerized gait mat. Analysis of variance
      demonstrated significant differences between patients and healthy individuals in
      step length, single support time and walking velocity (P<0.05). Within the CLBP
      group, stepwise regression analysis showed that FABQ (physical activity) and
      anticipated pain were the strongest predictors of velocity deficits in preferred
      and fast walking respectively. Anticipation and fear of pain accounted
      significantly for the velocity deficits in walking. Standard clinical gait
      assessments must incorporate psychological measures of pain experience.

PMID- 12799604
TI  - Comparison of changes in upper and lower extremity impairments and disabilities
      after stroke.
AB  - The aims of this study were to determine if the changes in impairment and
      disability measures for the upper and lower extremities were equivalent during
      the post-stroke rehabilitation period and whether the rates of change were
      maintained 6 months after discharge from rehabilitation. A prospective cohort
      study design was used. One-hundred-and-thirty-two people who had sustained a
      stroke and who were enrolled in an intensive functional rehabilitation programme
      were recruited. Upper and lower extremity impairments and disabilities were
      evaluated at admission, at discharge from rehabilitation and 6 months later.
      During active rehabilitation, the changes in both extremities were smaller for
      the impairment measures (standardized response mean (SRM), 0.37-0.63) than the
      disability measures (SRM, 0.76-1.05). While the changes in upper and lower
      extremities were equivalent for impairment measures, they were larger in the
      lower extremity for disability measures, indicating that the rate of functional
      improvement was faster in the lower extremity during active rehabilitation. After
      discharge, however, while the rate of motor recovery in the lower extremity
      dropped (SRM, 0.54-0.18), it was maintained in the upper extremity (SRM, 0.45 and
      0.42). Present findings indicate that functional (disability) measures improve
      faster than impairment measures in both extremities during the active
      rehabilitation period and suggest that motor recovery occurs at a different rate
      in the upper and lower extremities, with that of the upper extremity occurring
      later and extending into the period after discharge from active rehabilitation.

PMID- 12799605
TI  - Fear of exercise and health-related quality of life in patients with an
      implantable cardioverter defibrillator.
AB  - Several studies have reported improved survival rates thanks to the use of an
      implantable cardioverter defibrillator (ICD) in the treatment of patients with
      life-threatening arrhythmia. However, the effects of the ICD on health-related
      quality of life (HR-QoL) of these patients are not clear. The aim of this study
      is to describe HR-QoL and fear of exercise in ICD patients. Eighty-nine ICD
      patients from the University Hospital in Groningen, the Netherlands, participated
      in this study. HR-QoL was measured using the Rand-36 and the Quality of Life
      After Myocardial Infarction Dutch language version questionnaires. Fear of
      exercise was measured using the Tampa Scale for Kinesiophobia, Dutch version and
      the Fear Avoidance Beliefs Questionnaire, Dutch version. Association between
      outcome variables was analysed by linear regression analyses. Study results show
      that the HR-QoL of patients with ICDs in our study population is significantly
      worse than that of normal healthy people. Furthermore, fear of exercise is
      negatively associated with HR-QoL corrected for sex, age and number of years
      living with an ICD. After implantation of the ICD, patients with a clear fear of
      exercise should be identified and interventions should be considered in order to
      increase their HR-QoL.

PMID- 12799606
TI  - Sources of burdens on families of individuals with mental illness.
AB  - Families of individuals with mental illness face a range of practical and
      emotional stresses. Studies that have addressed the sources of these burdens are
      limited. Literature suggests that burdens could come from the stigmatizing
      attitudes towards individuals with mental illness and inadequate public
      resources. Nevertheless, how public attitudes and availability of public
      resources have affected the burden on patients' families remains to be studied.
      This study set out to explore the relationship between stigma, accessibility of
      mental health facilities and family burden through individual interviews of
      patients' relatives in order to understand the burden on mentally ill patients'
      relatives from their perspectives. Ten interviewees from two out-patient
      psychiatric clinics were recruited and interviewed. Each interviewee had at least
      one family member receiving out-patient psychiatric services. Altogether 11
      mentally ill patients were involved. Data analyses showed that much of the burden
      was related to stigma and to lack of mental health and rehabilitation services.
      Consequences included social isolation of the families, difficulties experienced
      by the mentally ill patients when trying to obtain competitive employment and
      financial difficulties. Subjective burden resulting from social stigma included
      frustration, anxiety, low self-esteem and helplessness. Implications of the
      findings to social policy and development of mental health services were
      discussed.

PMID- 12799607
TI  - Knee pain in people aged 80 years and older is not associated with gait parameter
      and functional performance.
AB  - We evaluated the differences in gait and functional performance between two
      groups of elderly people, one consisting of people between 65 and 79 years of age
      and the other consisting of people over 80 years of age. We analysed whether knee
      pain affected gait and looked at the functional performance of the timed 'up and
      go' (TUG) and functional reach (FR) tests. In 247 community-dwelling people aged
      65 years and older, consisting of 90 men and 157 women with a mean age of 80
      years (range 65-94 years), 47% had knee pain. Shorter stride, shorter step,
      slower speed, longer TUG and shorter FR were seen in the group aged 80 years and
      over compared with the group aged 65-79 years. Knee pain was associated with TUG,
      especially in the group aged 65-79 years. In the group aged 65-79 years with knee
      pain, a shorter stride and step length, a longer time required to hold a double
      stance, a slower walking speed and a longer TUG were shown. However, in the group
      aged 80 years and over, there was no significant difference between participants
      with and without knee pain for these parameters.

PMID- 12799608
TI  - Pain during in-patient rehabilitation after traumatic spinal cord injury.
AB  - In this prospective study, we surveyed the pain experience of 40 participants
      during the in-patient rehabilitation period following traumatic spinal cord
      injury (SCI). Twenty-eight patients (70% of the study population) had
      musculoskeletal (MS) pain or neuropathic (NP) pain. Pain responded positively to
      physical therapy and analgesics. A numerical pain scale decreased from a mean of
      6.36+/-1.7 on admission to 3.2+/-1.94 on discharge (P<0.001). Paraplegic patients
      were more likely to have MS pain (P=0.001) and NP pain (P=0.046). There was no
      relationship between completeness of injury, or spinal surgery, and type of pain
      encountered. There was also no significant difference in the modified Barthel
      index between patients with and without pain on admission and discharge. We
      conclude that pain is a common experience in SCI patients and that it can be
      reduced significantly by the end of in-patient rehabilitation.

PMID- 12799609
TI  - Evaluation of pressure and durability of a low-cost wheelchair cushion designed
      for developing countries.
AB  - Pressure sores are a medical problem for wheelchair users worldwide. In
      developing countries this problem is more critical because of lack of access to
      specialized technologies and medical assessment. Seat cushions to relieve
      pressure represent one of best ways to prevent pressure sores for people with
      spinal cord injury, amputation, cerebral palsy, and other disabilities that
      require use of wheelchairs for long periods of time. The purpose of this study
      was to evaluate the performance of a low cost cushion, called the Tuball,
      designed for low-income communities in developing countries. The Tuball is made
      from bicycle inner tubes and plastic balls. Its durability and pressure-relieving
      characteristics were compared with the ROHOTM cushion and the foam cushions now
      used in Brazil. A sample of 30 participants tested the three cushions: 15 persons
      with paraplegia and 15 matched able-bodied persons evaluated the capacity of the
      cushions to distribute pressure. This study also addressed the use of samples of
      persons without disabilities to test wheelchair cushions.The Tuball cushion
      provided significantly better pressure distribution than the foam cushion. A t
      test was used to compare disabled persons and non-disabled persons as samples in
      testing cushions. No difference between pressure distribution between non
      disabled and disabled participants was found in testing the ROHO cushion or the
      foam cushion. However, both capacities of pressure distribution and HICPR varied
      between non-disabled and disabled participants for the Tuball cushion. To
      determine the useful life of the Tuball cushion, a fatigue test was conducted to
      simulate sitting and transfer. Both the Tuball and ROHO cushions withstood the
      equivalent of at least 1 year of use, whereas the foam cushion broke down.

PMID- 12799610
TI  - Investigating the usability of a screen reader and mental models of blind users
      in the Windows environment.
AB  - The study explored blind users' mental models and strategies in coping with the
      Windows environment and investigated the relationship between users' mental
      models and usability problems they face when using a screen reader. The study
      found that blind users possess a functional or structural mental model or a
      combination thereof. Blind users also have a rich and highly procedural strategy
      for coping with a new Windows environment and application. Users' established
      mental models developed from using a familiar screen reader were found to
      contribute to problems in using a new screen reader.

PMID- 12799611
TI  - Visual problems among people with mental retardation.
AB  - Vision impairment can be a debilitating condition, affecting not only the social,
      emotional, mental and physical functioning of an individual, but also the
      individual's ability to perform basic and instrumental activities of daily
      living. Scant knowledge exists about visual impairment among people with mental
      retardation. The results of this prospective study were based on interviews and
      eye ophthalmologic screening of 106 adults with a moderate level of mental
      retardation, ranging in ages from 19 to 62 years. Findings show that only 3% of
      those interviewed recalled having had an eye examination, yet 24% reported that
      they had visual problems. In spite of the high probability of visual problems for
      this group, only 13% reported having glasses and 20% said they needed glasses;
      92% reported watching television but 22% stated they had difficulty seeing the
      TV; 62% of the respondents reported that they cook for themselves but 17%
      reported that visual problems affected their ability to perform this activity.
      Medical eye screening of the participants found that 79% had ocular problems -
      42% were in need of eyeglasses, 12% had a cataract problem requiring surgery and
      25% needed outpatient care at the local hospital. The study findings are
      discussed in terms of policy implications and service provision, and
      recommendations are made for additional research.

PMID- 12799612
TI  - Beneficial effects of water-based exercise in patients with chronic kidney
      disease.
AB  - The possible beneficial effect of regular aquatic exercise on cardiorespiratory,
      renal lipid parameters and oxidative stress status was studied in patients with
      mild to moderate renal failure. The exercise group did low-intensity aerobic
      exercise in the pool during a period of 12 weeks, twice a week, with sessions
      lasting for 30 min. Matched control participants remained sedentary. The results
      showed that in the exercise group all cardiorespiratory functional parameters
      improved and resting blood pressure lowered significantly. Proteinuria and
      cystatin-C were diminished significantly and glomerular filtration rate was
      enhanced. To evaluate the changes in oxidative stress status in the serum,
      products of lipid peroxidation (LPO) and serum glutathione values were measured.
      LPO was reduced significantly and reduced glutathione levels showed significant
      improvement after the exercise-conditioning programme. In the control group the
      data either remained the same or worsened in the same period of time. In
      conclusion, regular water-based exercise has beneficial effects on the
      cardiorespiratory, renal functional parameters and oxidative stress status in
      patients with moderate renal failure, and can be used in the complex
      rehabilitation of chronic renal failure patients, together with blood pressure
      control, dietary consultation, encouragement and education to prevent physical
      worsening and to postpone cardiovascular and renal atherosclerotic complications.

PMID- 12799613
TI  - Central muscarinic acetylcholine receptor availability in patients treated with
      clozapine.
AB  - Clozapine is the prototypical atypical antipsychotic. In vitro, clozapine
      antagonizes a broad range of receptors, including dopamine, serotonin and
      muscarinic acetylcholine receptors. In vivo, receptor occupancy studies have
      shown moderate dopamine D(2) receptor blockade as well as high serotonin 5HT(2)
      receptor blockade for clozapine. Using [I-123]IQNB SPECT, we explored the
      influence of clozapine on muscarinic receptors in vivo. Eight schizophrenia
      patients underwent a total of 12 [I-123]IQNB SPECT scans after treatment with low
      to moderate doses of clozapine (mean 210 mg/day, range 50-450 mg/day). Muscarinic
      receptor availability was determined for basal ganglia, cortex, thalamus, and
      pons. A group of 12 age- and sex-matched unmedicated schizophrenia patients was
      used for comparison. Compared to unmedicated patients, [I-123]IQNB binding was
      lower in all regions in subjects treated with clozapine and decreased with
      increasing dose. In patients treated with a daily clozapine dose of at least 200
      mg (mean 275+/-88 mg/day), these differences were highly significant (p <0.003)
      with mean reductions of muscarinic receptor availability of 45% for basal
      ganglia, 58% for cortex, 66% for pons, and 79% for thalamus. These preliminary
      data indicate that reduction of muscarinic receptor availability by clozapine can
      be measured in vivo and that moderate daily doses are associated with moderate to
      high reductions of muscarinic receptor availability. These results may explain,
      at least in part, the lack of extrapyramidal side effects as well as some side
      effects seen with clozapine.

PMID- 12799614
TI  - Increased expression of c-Jun transcription factor in cerebellar vermis of
      patients with schizophrenia.
AB  - In the cerebellar vermis of schizophrenic patients, our previous studies have
      revealed alterations in the mitogen-activated protein (MAP) kinase signaling
      cascade and downstream transcription factors within the c-fos promoter. Since the
      proteins of the Fos and Jun families of immediate-early genes dimerize to form
      activating protein (AP)-1, the present study was conducted to examine the
      expression of Jun transcription factors in schizophrenic and control subjects.
      Using Western blot analysis, we determined the protein levels of c-Jun, Jun B,
      and Jun D as well as the levels of c-jun mRNA by relative RT-PCR in post-mortem
      samples from cerebellar vermis. The expression of c-Jun protein and c-jun mRNA
      was significantly increased in the cerebellar vermis of patients with
      schizophrenia, whereas no significant differences were found in the expression of
      Jun B or Jun D proteins. Studies in rats indicated that the abnormal expression
      of c-Jun transcription factor observed in schizophrenic patients was not related
      to post-mortem intervals or chronic treatment with antipsychotic medications.
      This study provides new insights into cerebellar abnormalities of schizophrenia
      at the level of expression of c-Jun that target key genes associated with the MAP
      kinase cascade.

PMID- 12799615
TI  - Effects of repeated alcohol deprivations on operant ethanol self-administration
      by alcohol-preferring (P) rats.
AB  - We reported that repeated alcohol deprivations prolonged the expression of an
      alcohol-deprivation effect (ADE) under 24-h free-choice alcohol-drinking access
      and that the duration of the initial deprivation period had a positive effect of
      prolonging the duration of the ADE. In the present study, operant techniques
      (including progressive ratio measures) were used to examine the effects of
      initial deprivation length and number of deprivation cycles on the magnitude and
      duration of the ADE in alcohol-preferring (P) rats to test the hypothesis that
      repeated deprivations can increase the reinforcing effects of ethanol (ETOH).
      Adult male P rats were trained in two-lever operant chambers to self-administer
      15% ETOH (v/v) on a fixed-ratio 5 (FR-5) and water on a FR-1 schedule of
      reinforcement in daily 1-h sessions. Following 6 weeks of daily 1-h sessions, the
      P rats were randomly assigned to one of four groups (n=10/group): nondeprived or
      deprived of alcohol for 2, 5, or 8 weeks. Following this initial period, the
      deprived groups were given 15% ETOH again in the operant chambers for a 2-week
      period, following which they were deprived again for 2 weeks (all three deprived
      groups). Following the fourth deprivation, the rats underwent a progressive ratio
      test to determine the breakpoints (FR values) for the nondeprived and the
      deprived groups. Repeated deprivations increased both the magnitude and duration
      of the ADE as indicated by increased responding on the ETOH lever. However, the
      length of the initial deprivation had little effect on expression of the ADE
      except following the first deprivation, where an ADE was not observed for the 8
      week group. Breakpoint values for responding on the ETOH lever for all three
      deprived groups were two-fold higher than the value for the nondeprived group.
      The results suggest that repeated cycles of alcohol deprivation and alcohol
      access increased the reinforcing effects of ETOH in the P rats.

PMID- 12799617
TI  - Comparison of cognitive performances during a placebo period and an atypical
      antipsychotic treatment period in schizophrenia: critical examination of
      confounds.
AB  - Although previous studies report cognitive improvement following atypical
      antipsychotic administration in schizophrenia (SC), few placebo-controlled within
      subject studies with examination of confounds (symptom reduction, cooperation,
      learning, and outliers) have been reported. The present study examines the
      effects of atypicals and confounds upon cognition in SC. The hypothesis tested
      was that relative to placebo, atypicals as a general class of medication would
      elicit cognitive improvement in SC. In all, 19 patients with SC (15 males)
      completed the double-blind, counterbalanced, randomized within-subject study of
      the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or
      quetiapine) vs placebo administration upon cognitive performance in the domains
      of executive function, attention, memory, language, visual perception, and
      general intellect. Significant cognitive improvement during atypical
      antipsychotic administration relative to placebo withdrawal occurred in most
      cognitive domains with robust improvements in intelligence (p=0.001), memory
      (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated
      performances were excluded. These findings suggest that relative to placebo
      withdrawal, atypicals improve cognitive performance in SC. However, this finding
      may not be specific to atypicals, since analogous studies of typicals have not
      been performed.

PMID- 12799616
TI  - Delta sleep response to metyrapone in post-traumatic stress disorder.
AB  - Metyrapone blocks cortisol synthesis, which results in the stimulation of
      hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta
      sleep. We examined the effect of metyrapone administration on endocrine and sleep
      measures in male subjects with and without chronic PTSD. We hypothesized that
      metyrapone would result in a decrease in delta sleep and that the magnitude of
      this decrease would be correlated with the endocrine response. Finally, we
      utilized the delta sleep response to metyrapone as an indirect measure of
      hypothalamic CRF activity and hypothesized that PTSD subjects would have
      decreased delta sleep at baseline and a greater decrease in delta sleep induced
      by metyrapone. Three nights of polysomnography were obtained in 24 male subjects
      with combat-related PTSD and 18 male combat-exposed normal controls. On day 3,
      metyrapone was administered during normal waking hours until habitual sleep onset
      preceding night 3. Endocrine responses to metyrapone were measured in plasma
      obtained the morning following sleep recordings, the day before and after
      administration. Repeated measures ANOVAs were conducted to compare the endocrine
      and sleep response to metyrapone in PTSD and controls. PTSD subjects had
      significantly less delta sleep as indexed by stages 3 and 4, and total delta
      integrated amplitude prior to metyrapone administration. There were no
      differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD
      subjects had a significantly decreased ACTH response to metyrapone compared to
      controls. Metyrapone caused an increase in awakenings and a marked decrease in
      quantitative measures of delta sleep that was significantly greater in controls
      compared to PTSD. The decline in delta sleep was significantly associated with
      the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest
      that the delta sleep response to metyrapone is a measure of the brain response to
      increases in hypothalamic CRF. These data also suggest that the ACTH and sleep
      EEG response to hypothalamic CRF is decreased in PTSD.

PMID- 12799618
TI  - Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated
      schizophrenia subtype.
AB  - Evidence of immune activation has occasionally, but not consistently, been
      reported in schizophrenia. Investigations of cytokine abnormalities in serum, and
      occasionally in CSF, have yielded inconsistent results, which have been difficult
      to resolve. In such studies, schizophrenia has been assumed to consist of a
      single process rather than a group of disorders. This study assesses differences
      in the pro-inflammatory cytokine, interleukin-6 (IL-6) in the cerebrospinal fluid
      (CSF) in two previously delineated subtypes of schizophrenics ("delayed
      responders"(DR) (n=23) and "poor-responders" (PR) (n=8)) during periods of
      neuroleptic-free psychotic exacerbation, and in a comparison group of normal
      controls (n=14). The two response subtypes were separated by subsequent treatment
      response (greater/less than 60% reduction of SAPS scores from baseline during 6
      months of systematic treatment). The IL-6 assay, a sandwich enzyme-linked
      immunosorbent assay, was sensitive and reliable to detect IL-6 levels in the CSF
      of all subjects. CSF IL-6 was found to be significantly higher in the DR than the
      PR (P=0.017) and the controls (P=0.013). In addition to supporting the concept of
      heterogeneity in schizophrenia, this study also provides evidence that a central
      immune process may be occurring centrally in one subtype of schizophrenia.

PMID- 12799619
TI  - Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral
      prefrontal cortex of patients with schizophrenia.
AB  - Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an
      enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism
      of COMT, Val(108/158) Met, affects prefrontal function, and the high-activity Val
      allele has been reported to be a genetic risk factor for schizophrenia. We used
      in situ hybridization histochemistry to measure mRNA levels of COMT in the
      dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia (N=14) and
      of normal controls (N=15). While the groups did not differ in terms of mean level
      of COMT mRNA, there was a significantly different laminar pattern of COMT mRNA
      expression in pyramidal neurons (F=2.68, df=4,108, P <0.04); patients with
      schizophrenia had relatively lower levels in the superficial (II/III) layers and
      higher levels in the intermediate/deep (IV/V) layers (P&<0.01), while in
      controls, the expression was homogeneous across layers. Neither the mean level
      nor the laminar distribution of COMT mRNA was related to the Val(108/158) Met
      genotype, suggesting that the feedback regulation of mRNA level is not a
      compensation for the functional effect of the COMT polymorphism. The disease
      related laminar difference of COMT expression may be involved in dysregulation of
      dopamine signaling circuits in the DLPFC of patients with schizophrenia.

PMID- 12799620
TI  - Dopamine receptor subtypes selectively modulate excitatory afferents from the
      hippocampus and amygdala to rat nucleus accumbens neurons.
AB  - The nucleus accumbens (NAc) receives excitatory afferents from several cortical
      and limbic regions and dense dopaminergic inputs from the ventral tegmental area.
      We examined the effects of dopamine (DA) D1 and D2 selective drugs on the
      responses evoked in the NAc shell neurons recorded in vitro by stimulation of
      hippocampal and amygdaloid afferents. Activation of hippocampal and amygdaloid
      afferents induced excitatory postsynaptic responses that were depressed by bath
      application of DA in most of the cells recorded. The DA effect was substantially
      blocked by the D1 receptor antagonist SCH 23390, but not by the D2 receptor
      antagonist eticlopride. Moreover, the D1 receptor agonist SKF 38393, but not the
      D2 receptor agonist quinpirole, mimicked the effects of DA, although a small
      population of neurons exhibited a D1-mediated facilitation of the EPSP amplitude
      following fornix stimulation. These data demonstrate a DA receptor subtype
      specific modulation of glutamatergic inputs to the NAc, with D1 agonists
      attenuating amygdaloid inputs, whereas hippocampal-evoked responses were either
      depressed or potentiated by D1 stimulation. Such facilitation or attenuation of
      hippocampal afferents against a background of suppression of other afferents
      would permit the hippocampus to have a dominant influence over behavior during
      periods of exploration.

PMID- 12799621
TI  - Current position of 5HT3 antagonists and the additional value of NK1 antagonists;
      a new class of antiemetics.
AB  - The advent of the 5HT(3) receptor antagonists (5HT(3) antagonists) in the 1990 s
      and the combination with dexamethasone has resulted in acute emesis protection in
      70% of patients receiving highly emetogenic chemotherapy. Despite complete
      protection in the acute phase, however, 40% of patients as yet have symptoms in
      the delayed phase. 5HT(3) antagonists and dexamethasone are only modestly
      effective in this delayed phase. Moreover, the antiemetic protection over
      repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK(1)
      antagonists) belong to a new class of antiemetic agents that specifically target
      the NK(1) receptor, which is involved in both the acute and, particularly, the
      delayed phase of emesis. Clinical studies have demonstrated that the addition of
      NK(1) antagonists to dual therapy with a 5HT(3) antagonist plus dexamethasone
      improves the acute emesis protection by a further 10-15%. In the delayed phase,
      the proportion of patients remaining free of emesis increases by even 20-30%.
      Since the effectiveness of this triplet combination was found to be sustained
      over six cycles of chemotherapy, the chance for an individual patient to remain
      completely protected during both the acute and the delayed phase over six
      chemotherapy cycles is nearly doubled.

PMID- 12799622
TI  - Oral melphalan as a treatment for platinum-resistant ovarian cancer.
AB  - A large number of drugs have been used to treat recurrent ovarian cancer, yet
      there are few data that guide the physician's choice. Typically, the decision to
      re-treat with platinum-based therapy depends on the progression-free interval.
      However, the optimum agent for the treatment of platinum-resistant or refractory
      disease is not defined. In this study, we investigated the efficacy of oral
      melphalan in patients who have platinum refractory or resistant disease. A
      retrospective analysis was performed on 22 patients with ovarian carcinomas who
      had relapsed within 6 months of their platinum-based chemotherapy and were
      treated with oral melphalan. No objective responses were seen and the median
      overall survival was 3 months from commencement of therapy. Although the
      treatment was generally well tolerated, only two of the 22 patients managed to
      complete the planned six cycles of treatment. At the time of analysis, only two
      patients were alive. Other nonplatinum compounds have demonstrated response rates
      in the region of 20% in similar patient populations and it is unlikely that any
      positive responses could have been missed by chance (95% CI 0-15.4). The results
      of this study serve to eliminate oral melphalan as a treatment option in patients
      with platinum-resistant or refractory ovarian carcinoma.

PMID- 12799623
TI  - Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa,
      carboplatin): the Netherlands Cancer Institute experience.
AB  - High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment
      of several tumours. The relative efficacies of the different regimens have not
      been studied in comparative trials, but it is clear that toxicities differ
      significantly between them. We analysed the immediate and long-term toxicity in
      the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide
      6000 mg m(-2), carboplatin 1600 mg m(-2) (or 20 mg ml(-1) min under the curve
      (AUC)) both as daily 1 h infusion, thiotepa 480 mg m(-2) as twice daily 30 min
      infusion, all divided over 4 consecutive days) followed by peripheral blood
      progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n=86) or
      metastatic (n=4) breast cancer, or a germ cell tumour (n=8). Two patients (with a
      medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off
      protocol salvage regimen. The main toxicity was bone marrow suppression. Most
      patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the
      median time to neutrophil count 500 x 10(6) l(-1) and platelet count >20 x 10(9)
      l(-1) without transfusion independence was 10 (range 8-25) and 13 (8-60) days,
      respectively. The toxic death rate was 1%. Other frequent toxicities were
      neutropenic fever requiring antibiotics (n=65), central catheter-related
      infection (n=12) or a bleeding episode (n=48), mostly epistaxis (n=26).
      Reversible cardiac toxicity was seen in six patients and pulmonary events
      occurred in seven patients (infection (n=6), embolism (n=1)). Grade 3-4
      gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28%
      and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with
      cisplatin had a kidney transplantation 8 years after HD-CT. Late complications
      included reversible radiation pneumonitis (n=12) and chronic heart failure (n=2).
      We found five second solid malignancies and two myelodysplasias. In conclusion,
      the CTC regimen is associated with a moderate, mainly reversible, toxicity.
      Future studies need to compare the efficacy and toxicity of the different HD-CT
      regimens.

PMID- 12799624
TI  - Long-term results of intrathoracic chemohyperthermia (ITCH) for the treatment of
      pleural malignancies.
AB  - There is no standard treatment for patients with pleural malignancies. The aim of
      this prospective study was to investigate the toxicity and long-term results of a
      multimodality treatment consisting of surgery and intrathoracic chemohyperthermia
      (ITCH) for the treatment of patients with pleural malignancies. From January 1990
      to August 2000, 24 patients with mesothelioma (n=17), fibrosarcoma (n=3), pleural
      adenocarcinoma (n=3) and thymoma (n=1) were included. The mesothelioma stages
      were T1 or T2 in 10 cases, and T3 or T4 in seven cases. After cytoreductive
      surgery, ITCH was carried out for over 60 min, at inflow temperatures less than
      45 degrees C, either with mitomycin C (n=7) or cisplatin (n=5) or both (n=12).
      One patient died from major thoracic air leaks after major decortication and
      pleurectomy. Seven patients had complications, one pleural clotting necessitating
      reoperation. After a median follow-up of 89 months, the overall 1-year and 5-year
      survival rates were 74 and 27%, respectively. For T1 and T2 mesothelioma
      patients, the median survival was 41.3 months, and for T3 and T4 tumours, it was
      4.5 months (P=0.001). The fibrosarcoma patients are alive with no evidence of
      recurrence at 24, 43 and 54 months. In the conclusion, the combination of surgery
      with ITCH with mitomycin and/or cisplatin is relatively safe. This procedure may
      offer unexpected long-term survival in a selected group of patients (T1 and T2
      mesothelioma patients and fibrosarcoma patients).

PMID- 12799625
TI  - Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid
      (DMXAA), a novel antivascular agent.
AB  - The antitumour action of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is mediated
      through tumour-selective antivascular effects and cytokine induction. This
      clinical phase I trial was conducted to examine its toxicity, maximum tolerated
      dose, pharmacokinetics (PK) and pharmacodynamics (PD). A secondary objective was
      to assess its antitumour efficacy. DMXAA was administered every 3 weeks as a 20
      min i.v. infusion. Dose escalation initially followed a modified Fibonacci schema
      but was also guided by PK and toxicity. A total of 63 patients received 161
      courses of DMXAA over 19 dose levels ranging from 6 to 4900 mg m(-2). DMXAA was
      well tolerated at lower doses and no drug-related myelosuppression was seen.
      Rapidly reversible dose-limiting toxicities were observed at 4900 mg m(-2),
      including confusion, tremor, slurred speech, visual disturbance, anxiety, urinary
      incontinence and possible left ventricular failure. Transient prolongation of the
      corrected cardiac QT interval was seen in 13 patients evaluated at doses of 2000
      mg m(-2) and above. A patient with metastatic cervical carcinoma achieved an
      unconfirmed partial response at 1100 mg m(-2), progressing after eight courses.
      The results of PK and PD studies are reported separately. DMXAA has antitumour
      activity at well-tolerated doses.

PMID- 12799626
TI  - A dose- and schedule-finding study of darbepoetin alpha for the treatment of
      chronic anaemia of cancer.
AB  - A multicentre study evaluated the efficacy and safety of darbepoetin alpha
      administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic
      patients with cancer not concurrently receiving chemotherapy or radiotherapy. The
      QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts
      received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25,
      or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled,
      double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1))
      schedules (n=86), which enrolled different patients, took place after the QW
      schedule and were followed by a 12-week, open-label phase. Patients were
      evaluated for change in haemoglobin end points and red blood cell transfusions,
      serum darbepoetin alpha concentration, and safety. Selected domains of health
      related quality of life (HRQOL) were measured. With QW dosing, at least 70% of
      each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a
      concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(
      1) QW cohort, all patients achieved a haematopoietic response (100%; 95%
      confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had
      at least 60% of patients who achieved a haematopoietic response. Darbepoetin
      alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W.
      Less-frequent administration may benefit patients with chronic anaemia of cancer
      and their caregivers alike.

PMID- 12799628
TI  - A case-cohort study for the disease natural history of adenoma-carcinoma and de
      novo carcinoma and surveillance of colon and rectum after polypectomy:
      implication for efficacy of colonoscopy.
AB  - The disease natural history of colorectal neoplasm regarding two opposing
      theories, adenoma-carcinoma sequence and de novo carcinoma theory, is
      controversial and rarely quantified. The aims of this study are therefore to
      estimate the dwelling times of adenoma-carcinoma sequence by adenoma size and
      histological type, taking de novo carcinoma into account. The efficacy of
      polypectomy was therefore estimated making allowance for two pathways. A case
      cohort design, underpinning a cohort with 13 908 subjects (including 10 496
      normal subjects, 2652 polyps, 760 colorectal cancers) who underwent the first
      examination of colonoscopy between 1979 and 1998, was devised to estimate
      parameters associated with two opposing theories by randomly selecting 305 normal
      subjects, 300 patients with polyps, and 116 colorectal cancers from the cohort.
      All the 2652 polyps were linked to national cancer registry to ascertain 25
      invasive carcinomas after polypectomy. For the five-state model associated with
      adenoma size, dwelling times of small (0.6-1 cm) and large adenoma (>1 cm) are
      7.75 and 5.27 years for the model without considering de novo, and 17.48 and
      15.90 years for the model taking de novo carcinoma into account. Similar findings
      are observed for the model associated with histological type. The estimated
      proportions of de novo carcinoma are 31.87% from the model by adenoma size and
      27.81% from the model by histological type. Compared to size less than 5 mm,
      patients with adenoma size between 6 and 10 mm and patients with adenoma size
      larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70),
      respectively, for the risk of malignant transformation. There are similar
      findings for the model by histological type. The estimates of overall efficacy of
      colonoscopy in reducing CRC is 73% for the model allowing for de novo carcinoma
      and 88% for the model without considering de novo carcinoma theory. The efficacy
      of diminutive adenoma and small adenoma increases with follow-up years, whereas
      the efficacy of large adenoma decreases with follow-up years. In conclusion,
      about 30% of cancers arising from de novo sequence are demonstrated. This
      finding, together with the adenoma-carcinoma sequence associated with adenoma
      size and histological type, is important for the estimation of dwelling times,
      the efficacy of colonoscopy, and the surveillance of polyp after polypectomy.

PMID- 12799627
TI  - Twelve weeks of protracted venous infusion of fluorouracil (5-FU) is as effective
      as 6 months of bolus 5-FU and folinic acid as adjuvant treatment in colorectal
      cancer.
AB  - We performed a multicentre randomised trial to compare the efficacy and toxicity
      of 12 weeks of 5-fluorouracil (5-FU) delivered by protracted intravenous infusion
      (PVI 5-FU) against the standard bolus regimen of 5-FU and folinic acid (5-FU/FA)
      given for 6 months as adjuvant treatment in colorectal cancer. A total of 716
      patients with curatively resected Dukes' B or C colorectal cancer were randomised
      to 5-FU/FA (5-FU 425 mg m(-2) i.v. and FA 20 mg m(-2) i.v. bolus days 1-5 every
      28 days for 6 months) or to PVI 5-FU alone (300 mg m(-2) day for 12 weeks). With
      a median follow-up of 19.8 months, 133 relapses and 77 deaths have been observed.
      Overall survival did not differ significantly (log rank P=0.764) between patients
      receiving 5-FU/FA and PVI 5-FU (3-year survival 83.2 vs 87.9%, respectively).
      Patients in the 5-FU/FA group had significantly worse relapse-free survival (RFS,
      log rank P=0.023) compared to those receiving PVI 5-FU (3-year RFS, 68.6 vs 80%,
      respectively). Grades 3-4 neutropenia, diarrhoea, stomatitis and severe alopecia
      were significantly less (P<0.0001) and global quality of life scores
      significantly better (P&<0.001) for patients in the PVI 5-FU treatment arm. In
      conclusion, infused 5-FU given over 12 weeks resulted in similar survival to
      bolus 5-FU and FA over a 6 month period, but with significantly less toxicity.

PMID- 12799629
TI  - Tumour cell contamination of autologous stem cells grafts in high-risk
      neuroblastoma: the good news?
AB  - We analysed the effect of graft-contaminating tumour cells on the long-term
      survival of 24 patients with high-risk neuroblastoma and found that patients
      whose grafts contained detectable neuroblastoma cells had a significantly higher
      probability of survival than did patients with no detectable tumour cells.
      Estimated contamination of the graft by more than 2000 tumour cells was
      associated with a significantly higher probability of survival than contamination
      with fewer tumour cells. We hypothesise that the presence of a critical number of
      graft-contaminating neuroblastoma cells can elicit a protective antitumour immune
      response after autologous transplantation.

PMID- 12799630
TI  - Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma
      specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular
      carcinoma markers complementary to alpha-fetoprotein.
AB  - Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma
      specific band of serum gamma-glutamyl transferase (GGTII), and alpha-fetoprotein
      (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC)
      and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HCC
      patients was higher than that in cirrhotic patients. A total of 53.3% of patients
      (64 out of 120) with HCC had PIVKAII levels above 40 mAU ml(-1). However, only 13
      patients with cirrhosis had higher PIVKA II levels. Of 32 small HCC patients, 13
      (40.6%) had PIVKAII values above 40 mAU ml(-1). An increased concentration of AFP
      (i.e. 20 ng ml(-1)) was observed in 70 out of 120 (58.3%) patients with HCC and
      in 33 out of 90 (36.7%) patients with cirrhosis. Positive GGTII was found in
      74.0% (89 out of 120) cases of HCC (sensitivity), in 16 of 90 cases of cirrhosis,
      and 14 of 32 (43.8%) small HCC patients had GGTII positive. No significant
      correlation was found between serum levels of AFP and PIVKAII. Combining the
      information from PIVKAII, AFP, and GGTII significantly increases the sensitivity
      over AFP alone. PIVKAII and GGTII are useful tumour markers complementary to AFP
      for diagnosis of HCC.

PMID- 12799631
TI  - Papanicolaou tests and molecular analyses using new fluid-based specimen
      collection technology in 3000 Japanese women.
AB  - A fluid-based Papanicolaou test has been established to improve sample collection
      and preparation. This study was the first large-scale investigation in Japan to
      examine the feasibility of using fluid-based Papanicolaou specimens to detect
      human papillomavirus (HPV) using Hybrid Capture II and polymerase chain reaction
      (PCR). Three thousand patients who visited Keio University Hospital between
      October 2000 and February 2001 were enrolled in the study. The results of the
      fluid-based Papanicolaou tests corresponded well with those of conventional
      Papanicolaou smears (96.8% concordance). The sensitivities of cervical neoplasia
      detection using the fluid-based Papanicolaou test (73.9%) and Hybrid Capture II
      (76.3%, P=0.55) were not significantly different. Among the cervical
      intraepithelial neoplasia 3 and squamous cell carcinoma specimens, HPV 16 and HPV
      52 were predominantly detected using the PCR method. Although some DNA samples
      extracted from the fluid-based specimens were degradaded, PCR and direct
      sequencing could be performed without difficulty even after 1 year of specimen
      storage. We conclude that fluid-based Papanicolaou specimens can be applied to
      investigate HPV infection.

PMID- 12799632
TI  - Rapid detection of allelic losses in brain tumours using microsatellite repeat
      markers and high-performance liquid chromatography.
AB  - High-performance liquid chromatography (HPLC) is a recently introduced high
      capacity automated method for detecting unknown mutations (denaturing HPLC) or
      for sizing DNA fragments under nondenaturing conditions. We have adapted the HPLC
      method for detection of loss of heterozygosity (LOH) and used glial tumours as a
      model to evaluate its sensitivity and specificity in comparison to conventional
      denaturing polyacrylamide gel electrophoresis. A total of 20 oligodendrogliomas
      (grades II and III), and five astrocytic tumours (grades III and IV) were
      analysed using 14 polymorphic microsatellite markers mapping to regions on
      chromosomes 1p, 19q, and 10q using both DNA-HPLC and denaturing gel
      electrophoresis. This study demonstrated complete concordance between both
      methods. However, unlike gel electrophoresis, HPLC is automated, does not require
      post-PCR processing, and does not require hazardous radioactive or expensive
      fluorescent labelling. Our data suggest that HPLC is a reliable and sensitive
      method for detection of allelic losses in tumour samples and it is a favourable
      alternative for high-sensitivity LOH detection in both research and diagnostic
      environments.

PMID- 12799634
TI  - The combination of angiogenesis and blood vessel invasion as a prognostic
      indicator in primary breast cancer.
AB  - This study was undertaken to examine the interaction between the combination of
      angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to
      determine the prognostic significance of that combination in predicting 20-year
      relapse-free survival (RFS) and overall survival (OS) rates in primary breast
      cancer. Five hundred and nine patients were studied. We investigated 11 factors,
      including average microvessel count (AMC)/BVI, lymph-node status (n), clinical
      tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53,
      proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI),
      apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by
      both factor VIII-related antigen and elastica van Gieson staining. To evaluate
      the best objective method to quantify microvessel density in angiogenesis, AMC
      was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%,
      respectively. That of both AMC-high and BVI-positive tumours was 10.1%.
      Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN
      were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI
      was the strongest independent prognostic factor for 20-year RFS (relative risk
      (RR)=5.5; P<0.0001) and for 20-year OS (RR=4.3; P<0.0001). Lymph-node status was
      still considered a powerful prognostic indicator; however, the combination of AMC
      and BVI provided more reliable prognostic information than lymph-node status for
      haematogenous dissemination.

PMID- 12799633
TI  - Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver
      cancer.
AB  - Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were
      measured in sera from 187 patients with primary liver cancer (164 with
      hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC))
      and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were
      significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng
      ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U
      test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using
      cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)),
      CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used
      markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%),
      and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from
      stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration
      increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1
      represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA
      21-1 reflected differences in tumour burden, suggesting applicability to staging
      and follow-up.

PMID- 12799635
TI  - Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric,
      and hepatocellular carcinomas.
AB  - Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which
      indicates the existence of broad-range tumour-suppressor gene(s) at this locus.
      Truncating mutations in the ST7 gene at this locus are seen frequently in primary
      colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a
      novel candidate gene for the tumour suppressor at this locus. However, more
      recent studies have reported that ST7 mutations are infrequent or absent in
      primary cancer and cell lines. To ascertain the frequency of mutations of the ST7
      gene in cancer cells, we examined mutations in the ST7 coding sequence in 48
      colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain
      reaction-single-strand conformational polymorphism and direct sequencing. We
      detected somatic mutations, which were located near the exon-intron junction in
      intron 8, in only three out of 144 cases. We conclude that mutations in the ST7
      gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.

PMID- 12799636
TI  - DNA copy number changes in young gastric cancer patients with special reference
      to chromosome 19.
AB  - Only a few cytogenetic and genetic studies have been performed in gastric cancer
      patients in young age groups. In the present study we used the comparative
      genomic hybridisation (CGH) method to characterise frequent DNA copy number
      changes in 22 gastric cancer patients of 45 years or younger and three gastric
      cancer cell lines established from patients younger than 45 years. Analysis of
      DNA copy number changes revealed frequent DNA copy number increases at
      chromosomes 17q (52%), 19q (68%) and 20q (64%). To confirm the CGH results and to
      characterise the amplicon region on the most frequently amplified chromosome,
      chromosome 19, we carried out fluorescence in situ hybridisation (FISH) analysis
      and Southern blot analysis. Fluorescence in situ hybridisation with the bacterial
      artificial chromosome (BAC) clone mapped to 19q12 indicated a copy number
      increase in all eight tumour specimens studied. Southern blot analysis of six
      tumour specimens and three tumour cell lines, with five probes mapped to the
      19q12-13.2 region, suggested cyclin E to be one of the candidate target genes in
      the 19q region for gastric cancer tumorigenesis. Cyclin E protein overexpression
      was verified in tumours with amplification on chromosome 19. Further studies are
      required to investigate the biological and clinical significance of 19q amplicon
      and cyclin E upregulation in gastric cancer of young patients.

PMID- 12799637
TI  - Linkage and association analysis of nevus density and the region containing the
      melanoma gene CDKN2A in UK twins.
AB  - Rare mutations in the CDKN2A gene are highly penetrant for melanoma. Density of
      nevi is under strong genetic control and high density is a potent risk factor for
      melanoma. We used linkage and association analysis in adolescent twins from the
      UK to examine the hypothesis that the region containing the CDKN2A gene also
      contains a quantitative trait locus influencing normal nevus development. Five
      markers in the CDKN2A region were genotyped in 115 dizygotic twin pairs, and one
      marker (D9S942) was genotyped in 103 monozygotic twin pairs, all of whom had been
      phenotyped for nevus density. Linkage analysis showed no evidence of a
      quantitative trait locus influencing nevus density in this chromosomal region. A
      model partitioning the variation in phenotype into within- and between-twin pair
      components showed weak evidence of association between higher nevus density and
      longer mean length of the two D9S942 alleles (P=0.01). This relation, which was
      also observed in an earlier Australian twin study, could be because of the
      linkage disequilibrium between D9S942 and a neighbouring functional locus.
      Further investigation of this region is warranted in large-scale linkage or
      association studies.

PMID- 12799638
TI  - Genetic alterations in primary osteosarcoma from 54 children and adolescents by
      targeted allelotyping.
AB  - At present, the only recognised prognostic factor for primary osteosarcoma is the
      histological response to preoperative chemotherapy. Our study was designed to
      identify new diagnostic markers that could eventually have a prognostic value. A
      total of 54 patients under 20 years of age with primary osteosarcomas were
      studied while under treatment by the French Society of Paediatric Oncology OS 94
      protocol. Paired normal and biopsy samples were collected. In addition, surgical
      resection specimens, following preoperative chemotherapy, were obtained in 13
      cases. After genomic DNA extraction, an allelotyping analysis targeting
      microsatellites linked to Rb and p53 genes, and 9p21, 7q31 and 5q21 regions was
      performed. In all, 94% of the samples at diagnosis showed allelic imbalance and
      the biopsies were highly rearranged except for the microsatellite targeting 7q31.
      The same panel was highly informative at surgical resection. Microsatellites
      investigating Rb, p53 and the 9p21 region were particularly altered without a
      significant correlation with prognosis. On the other hand, the alteration of the
      7q31 locus at diagnosis was significantly correlated with a worse prognosis and a
      new frequently altered locus, 5q21, was described. In conclusion, this panel
      allowed us to characterise paediatric osteosarcomas. Correlation of prognosis
      with the altered 7q31 region could be a useful tool and further studies are
      required to confirm the importance of 5q21.

PMID- 12799639
TI  - E-cadherin involved in inactivation of WNT/beta-catenin signalling in urothelial
      carcinoma and normal urothelial cells.
AB  - Constitutive activation of WNT signalling through beta-catenin, which leads to
      increased transcription of TCF/beta-catenin target genes, is crucial in the
      development of many human tumour types including colorectal carcinoma and
      hepatoma. Its role in urothelial cancer (TCC) is unclear, since typical
      activating mutations are not found. We therefore determined the activity of a
      beta-catenin/TCF-dependent promoter in proliferating normal uroepithelial cells
      and seven TCC cell lines, using a hepatoma line with oncogenic beta-catenin as a
      control. Neither normal urothelial cells nor TCC lines exhibited activity under
      normal growth conditions. In normal cells and 5/7 TCC lines, even transfection of
      activated beta-catenin did not restore promoter activity, suggesting repression
      of beta-catenin/TCF activity. TCF mRNAs and total beta-catenin protein levels did
      not differ qualitatively between inducible and noninducible cell lines, but E
      cadherin expression was lacking or low in inducible TCC lines. In these,
      cotransfection of E-cadherin diminished activation of the TCF-dependent promoter
      by beta-catenin. Our results make constitutive WNT/beta-catenin signalling in TCC
      appear unlikely, thereby explaining the lack of reported mutations. However,
      decreased E-cadherin expression occurring in many TCC, often as a consequence of
      promoter hypermethylation, may confer inappropriate responsiveness to WNT
      factors.

PMID- 12799640
TI  - Possible associations between ELF electromagnetic fields, DNA damage response
      processes and childhood leukaemia.
AB  - Epidemiology has shown an association between exposure to extremely low frequency
      (ELF) electromagnetic fields (EMF) and childhood leukaemia. The causal nature and
      biological basis of this association are however questionable. Studies with
      aneuploid cell lines raised the hypothesis that ELF EMF may act as a
      coleukaemogen by compromising DNA damage response to genotoxic agents such as
      ionising radiation. We examined this hypothesis using gamma-ray-induced dicentric
      chromosome exchange in human lymphocytes. The results from 12 h post-gamma-ray
      exposure to fields of 0.23, 0.47 and 0.7 mT provide no support to the hypothesis.
      The power of the study was sufficient to exclude an ELF enhancement of
      chromosomal exchange of 10-15% (2SE).

PMID- 12799641
TI  - Paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons in vivo
      reducing oxaliplatin toxicity.
AB  - Paclitaxel and oxaliplatin are promising drugs for combination trials but both
      induce peripheral neurotoxicity. To investigate this toxicity, 10-week-old female
      Wistar rats were given single intraperitoneal doses of paclitaxel and
      oxaliplatin, alone or in combination. Neurotoxicity was assessed by L5 dorsal
      root ganglion morphometry and H-reflex-related sensory nerve conduction velocity.
      Platinum concentrations in dorsal root ganglia and plasma were measured by
      inductively coupled plasma mass spectrometry. Dorsal root ganglion nucleolus size
      was significantly increased following single doses of paclitaxel of 10 and 20 mg
      kg(-1) at 24 h and 6 days (P<0.02). In contrast, dorsal root ganglion nucleolus
      size was significantly decreased following single doses of oxaliplatin ranging
      from 3 to 30 mg kg(-1) at time points ranging from 2 h to 14 days. Sensory nerve
      conduction velocity was altered after a single dose of oxaliplatin but not after
      paclitaxel. In combination with oxaliplatin, paclitaxel did not alter the plasma
      pharmacokinetics or dorsal root ganglion accumulation of oxaliplatin-derived
      platinum. However, prior paclitaxel inhibited oxaliplatin-induced reductions of
      dorsal root ganglion nucleolar diameter (P<0.02). Sensory nerve conduction
      velocity was reduced after oxaliplatin alone (P&<0.05) but unchanged when
      paclitaxel was given before oxaliplatin. In conclusion, paclitaxel induces
      nucleolar enlargement in dorsal root ganglion neurons after pharmacologically
      relevant doses in vivo and reduces oxaliplatin nucleolar damage and
      neurotoxicity.

PMID- 12799642
TI  - Vitamin E analogues as inducers of apoptosis: structure-function relation.
AB  - Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic
      agent with antineoplastic activity. As modifications of the vitamin E (VE)
      molecule may affect its apoptogenic activity, we tested a number of newly
      synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with
      lower number of methyl substitutions on the aromatic ring were less active than
      alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced
      the activity, while it was lower for the glutaryl esters. Methylation of the free
      succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the
      apoptogenic activity of the parent compounds. Both Trolox and its succinylated
      derivative were inactive. alpha-tocotrienol (alpha-T3 H) failed to induce
      apoptosis, while gamma-T3 H was apoptogenic, and more so when succinylated.
      Shortening the aliphatic side chain of gamma-T3 by one isoprenyl unit increased
      its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings
      show that modifications of different functional moieties of the VE molecule can
      enhance apoptogenic activity. It is hoped that these observations will lead to
      the synthesis of analogues with even higher apoptogenic and, consequently,
      antineoplastic efficacy.

PMID- 12799643
TI  - Increased expression of cyclin E is associated with an increased resistance to
      doxorubicin in rat fibroblasts.
AB  - Cell cycle progression in eukaryotic cells is regulated by a family of cyclin
      dependent kinases (CDKs). Cyclin E is a regulatory subunit of CDK2 and drives
      cells from G1 to S phase. Increased expression of cyclin E is a frequent event in
      human malignancies and has been associated with poor prognosis in various
      cancers. In this study, we evaluated the effects of cyclin E-overexpression on
      the sensitivity of rat fibroblasts to anticancer drugs. Cyclin E-overexpressing
      cells were less sensitive to doxorubicin-induced inhibition of cell growth but
      not to other antineoplastic drugs, such as paclitaxel, vincristine, etoposide and
      methotrexate. Cyclin E-overexpressing fibroblasts also displayed a reduction in
      ROS levels and a significantly lower increase following doxorubicin treatment
      compared with vector control cells. The expression of manganese superoxide
      dismutase (MnSOD) and its activity were increased (about 1.3-fold) in cyclin E
      overexpressing derivatives compared with control cells. These results suggest
      that cyclin E overexpression might reduce tumour cells sensitivity to doxorubicin
      by affecting the expression of MnSOD and that determination of cyclin E
      expression levels might help to select patients to be treated with an
      anthracycline-based antineoplastic therapy.

PMID- 12799644
TI  - Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance
      associated protein-overexpressing human cancer cell lines.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analogue that is
      activated by deoxycytidine kinase (dCK) to its monophosphate and subsequently to
      its triphosphate dFdCTP, which is incorporated into both RNA and DNA, leading to
      DNA damage. Multidrug resistance (MDR) is characterised by an overexpression of
      the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance
      associated protein (MRP). Gemcitabine was tested against human melanoma, non
      small-cell lung cancer, small-cell lung cancer, epidermoid carcinoma and ovarian
      cancer cells with an MDR phenotype as a result of selection by drug exposure or
      by transfection with the mdr1 gene. These cell lines were nine- to 72-fold more
      sensitive to gemcitabine than their parental cell lines. The doxorubicin
      resistant cells 2R120 (MRP1) and 2R160 (P-gP) were nine- and 28-fold more
      sensitive to gemcitabine than their parental SW1573 cells, respectively (P<0.01),
      which was completely reverted by 25 micro M verapamil. In 2R120 and 2R160 cells,
      dCK activities were seven- and four-fold higher than in SW1573, respectively,
      which was associated with an increased dCK mRNA and dCK protein. Inactivation by
      deoxycytidine deaminase was 2.9- and 2.2-fold decreased in 2R120 and 2R160,
      respectively. dFdCTP accumulation was similar in SW1573 and its MDR variants
      after 24 h exposure to 0.1 micro M gemcitabine, but dFdCTP was retained longer in
      2R120 (P<0.001) and 2R160 (P<0.003) cells. 2R120 and 2R160 cells also
      incorporated four- and six-fold more [(3)H]gemcitabine into DNA (P<0.05),
      respectively. P-glycoprotein and MRP1 overexpression possibly caused a cellular
      stress resulting in increased gemcitabine metabolism and sensitivity, while
      reversal of collateral gemcitabine sensitivity by verapamil also suggests a
      direct relation between the presence of membrane efflux pumps and gemcitabine
      sensitivity.

PMID- 12799645
TI  - Zoledronic acid induces antiproliferative and apoptotic effects in human
      pancreatic cancer cells in vitro.
AB  - Bisphosphonates (BPs) are an emerging class of drugs mostly used in the
      palliative care of cancer patients. We investigated the in vitro activity of the
      most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival
      of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1).
      Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore
      appears to be a suitable target for BPs that interfere with the prenylation of
      small GTP-binding proteins such as p21(ras). We found that ZOL induces growth
      inhibition (IC(50):10-50 micro M) and apoptotic death of PC cells. The
      proapoptotic effect was correlated to cleavage/activation of caspase-9 and
      poly(ADP)-ribose polymerase, but not of caspase-3. Moreover, we studied the
      p21(ras) signalling in cells exposed to ZOL and detected a reduction of p21(ras)
      and Raf-1 content and functional downregulation of the terminal enzyme
      ERK/MAPkinase and of the pKB/Akt survival pathway. Finally, we observed that ZOL
      induces significant cytoskeletal rearrangements. In conclusion, we demonstrated
      that ZOL induces growth inhibition and apoptosis on PC cells and interferes with
      growth and survival pathways downstream to p21(ras). These findings might be
      relevant for expanding application of BPs in cancer treatment.

PMID- 12799647
TI  - Inhibition of epidermoid carcinoma A431 cell growth and angiogenesis in nude mice
      by early and late treatment with a novel dextran derivative.
AB  - We investigated the effect of a new dextran derivative, phenylacetate
      carboxymethyl benzylamide dextran (NaPaC), on epidermoid carcinoma A431 cells
      secreting a large quantity of angiogenic factor, vascular endothelial growth
      factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells
      (IC(50)=5 micro M). Also, NaPaC decreased the binding of radiolabelled VEGF(165)
      to endothelial cells (IC(50)=0.2 micro M). In vivo, we explored the effects of
      NaPaC (15 mg kg(-1)) on A431 xenograft growth starting the drug administration at
      the time of tumour cell inoculation (early treatment) and 1 week later, when
      tumours were well established (late treatment). Early treatment was more
      efficient on tumour inhibition (70% vs control) than late treatment (50% vs
      control). Early and late NaPaC-treatment increased the aponecrosis in tumour by
      70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour
      endothelial cell density in the same manner. In contrast, vessel area was
      decreased only when NaPaC was injected early (35%). These results show that NaPaC
      has a potent inhibitory effect, dependent on treatment outset, on epidermoid
      carcinoma growth associated with an intratumour microvascular network diminution
      and an aponecrosis increase. As this drug is nontoxic at efficient dose, it
      offers interesting perspectives for the therapy of malignant lesions.

PMID- 12799646
TI  - Effect of antivascular endothelial growth factor treatment on the intratumoral
      uptake of CPT-11.
AB  - Promising preclinical activity with agents blocking the function of vascular
      endothelial growth factor (VEGF) has been observed in various cancer types,
      especially with combination therapy. However, these drugs decrease microvessel
      density, and it is not known whether this reduced vessel density (VD) results in
      decreased delivery of concomitantly administered classical anticancer drugs. We
      designed an in vivo study to investigate the relation between VEGF-blocking
      therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude
      NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb
      A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the
      animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more
      pronounced with potentially functional large vessels than endothelial cords.
      Interestingly, a trend to increased intratumoral CPT-11 concentration was
      observed (P=0.09). In parallel, we measured an increase in tumour perfusion, as
      estimated by high-performance liquid chromatography determination of
      intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was
      at least equally effective with or without pretreatment with A4.6.1. These data
      suggest that tumour vascular function and tumour uptake of anticancer drugs
      improve with VEGF-blocking therapy, and indicate the relevance for further
      investigations.

PMID- 12799648
TI  - Interferon-gamma suppresses S100A4 transcription independently of apoptosis or
      cell cycle arrest.
AB  - The S100A4 protein has been associated with increased metastatic capacity of
      cancer cells, and recent studies have suggested a correlation between the
      expression level of S100A4 and the prognostic outcome for patients with various
      types of cancer. The knowledge about the mechanisms underlying the metastasis
      promoting effects is still limited, and the aim of the present study was to
      elucidate signal transduction pathways involved in the regulation of S100A4.
      After treatment of human carcinoma cells with interferon-gamma (IFN-gamma), we
      observed downregulation of S100A4 both at mRNA and protein levels. The effect was
      not dependent on IFN-gamma-induced apoptosis or IFN-gamma-mediated cell cycle
      arrest. Moreover, IFN-gamma-mediated decrease in mRNA stability could not account
      for the observed decrease in S100A4 transcript level. Finally, microarray
      analysis suggests ISGF3G, ETV5, ZNF133 and CEBPG as possible candidate genes
      involved in IFN-gamma-mediated repression of S100A4.

PMID- 12799649
TI  - Antibodies against human papillomavirus type 16 (HPV-16) and conjunctival
      squamous cell neoplasia in Uganda.

PMID- 12799652
TI  - Bioassay of anilazine for possible carcinogenicity (CAS No. 101-05-3).
AB  - A bioassay of anilazine for possible carcinogenicity was conducted by
      administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
      Groups of 50 rats and 50 mice of each sex were administered anilazine at one of
      two doses, either 500 or 1,000 ppm, for 103 weeks and then observed for 1-6
      additional weeks. Matched controls consisted of 25 untreated rats and 25
      untreated mice of each sex. All surviving rats were killed at 103-104 weeks; all
      surviving mice were killed at 107-109 weeks. Administration of the anilazine had
      no appreciable effect on body weight in the rats and female mice; however, there
      was a decreased gain in mean body weight in the dosed male mice. Survival also
      was essentially unaffected. Survival in all groups of dosed and control rats and
      mice was at least 80% at the end of 90 weeks on study, except for the male
      control mice; thus, sufficient numbers of animals were at risk in most groups for
      development of late-appearing tumors. No tumors occurred in dosed rats or mice of
      either sex at incidences that were significantly higher than those in
      corresponding controls. Male and female rats and female mice may have been able
      to tolerate higher doses. It is concluded that under the conditions of this
      bioassay, anilazine was not carcinogenic for either Fischer 344 rats or B6C3F1
      mice.

PMID- 12799653
TI  - Bioassay of triphenyltin hydroxide for possible carcinogenicity.
AB  - A bioassay of triphenyltin hydroxide for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. Triphenyltin hydroxide was administered
      in the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The high and low concentrations of triphenyltin
      hydroxide were, respectively, 75 and 37.5 ppm for rats and mice. After a 78-week
      period of compound administration, there was an additional observation period of
      26 weeks for both species. Twenty animals of each sex and species were placed on
      test as controls. For male mice, there was a significant positive association
      between dosage and mortality. In both species, however, adequate numbers of
      animals survived sufficiently long to be at risk from late-developing tumors.
      Except for a slight depression of mean body weight gain in male rats and female
      mice, compound-related mean body weight depression was not observed in either
      species. In female rats no significant accelerated mortality, retardation of
      growth, or other signs of toxicity were associated with the dietary
      administration of triphenyltin hydroxide. Therefore, it is possible that the
      compound was not administered at the maximum tolerated concentrations. No tumors
      occurred at a significantly higher incidence in dosed rats or mice than in
      controls. Under the conditions of this bioassay, there was no evidence for the
      carcinogenicity of triphenyltin hydroxide to Fischer 344 rats or B6C3F1 mice.

PMID- 12799654
TI  - Bioassay of sulfisoxazole for possible carcinogenicity.
AB  - A bioassay of sulfisoxazole for possible carcinogenicity was conducted by
      administering the chemical by gavage to Fischer 344 rats and B6C3F1 mice. Groups
      of 50 rats of each sex and 50 mice of each sex were administered sulfisoxazole
      suspended in aqueous 0.5% carboxymethyl cellulose 7 days per week at one of two
      doses, either 100 or 400 mg/kg body weight for the rats and either 500 or 2,000
      mg/kg for the mice. Vehicle controls consisted of groups of 50 rats of each sex
      and 50 mice of each sex that were administered only the aqueous 0.5%
      carboxymethyl cellulose. Untreated controls consisted of groups of 50 rats of
      each sex and 50 mice of each sex. The dosed groups of the rats and mice were
      administered the chemical by gavage for 103 weeks, then observed for 1 to 3
      additional weeks; the vehicle-control groups were similarly administered 0.5%
      carboxymethyl cellulose alone. All surviving rats and mice were killed at weeks
      104 to 106. Mean body weights of high-dose male rats and female mice were
      slightly lower than those of corresponding vehicle controls during the last 40 to
      50 weeks of the bioassay; mean body weights of dosed female rats and male mice
      were unaffected. Survival rates were unaffected by the test chemical, and
      adequate numbers of animals were at risk for the development of late-appearing
      tumors. No tumors occurred in the dosed groups of rats or mice of either sex at
      incidences that were significantly higher than those of the vehicle-control
      groups. It is concluded that under the conditions of this bioassay, sulfisoxazole
      was not carcinogenic for either Fischer 344 rats or B6C3F1 mice

PMID- 12799655
TI  - Bioassay of diazinon for possible carcinogenicity.
AB  - A bioassay of diazinon for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats and 50 mice of each sex were administered diazinon at one of two doses,
      either 400 or 800 ppm for the rats and either 100 or 200 ppm for the mice, for
      103 weeks and were then observed for an additional 1 or 2 weeks. Matched controls
      consisted of groups of 25 untreated rats and 25 untreated mice of each sex. All
      surviving animals were killed at the end of 104 or 105 weeks. There was no
      appreciable effect of administration of diazinon on mean body weights of rats or
      mice of either sex. Mortality was not increased in any of the dosed groups of
      rats or mice, when related to that in the corresponding controls, and survival
      was 84% or greater in all dosed and control groups of animals at week 78. Some
      hyperactivity was noted in the dosed groups of both species; however, both the
      rats and mice may have been able to tolerate higher doses. Sufficient numbers of
      animals were at risk in all groups for the development of late-appearing tumors.
      No tumors occurred in any of the dosed groups of rats or mice of either sex at
      incidences that could clearly be related to the administration of diazinon. It is
      concluded that under the conditions of this bioassay, diazinon was not
      carcinogenic for F344 rats or B6C3F1 mice of either sex

PMID- 12799656
TI  - Bioassay of aldicarb for possible carcinogenicity.
AB  - A bioassay of aldicarb for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats and 50 mice of each sex were administered aldicarb at one of two doses,
      either 2 or 6 ppm, for 103 weeks and then observed for an additional 0 to 2
      weeks. Matched controls consisted of 25 untreated rats and 25 untreated mice of
      each sex. All surviving animals were killed at weeks 103 to 105. Mean body
      weights of the dosed male and female rats were essentially the same as those of
      the corresponding controls. Mean body weights of the dosed male and female mice
      also were essentially the same as those of corresponding controls. Hyperactivity
      was noted in the dosed groups of mice. Survival was not affected significantly in
      dosed groups of either the rats or the mice and was 72% or greater in all dosed
      or control groups at week 90. Sufficient numbers of animals were at risk for the
      development of late-appearing tumors. No tumors occurred in either the rats or
      mice at incidences that could clearly be related to administration of the test
      chemical. In both rats and mice, however, there was no indication either through
      weight depression or early mortality that maximum tolerated dose levels were
      used. Therefore, the studies may not have been conducted using maximum
      sensitivity for the assessment of the possible carcinogenicity of aldicarb. It is
      concluded that under the conditions of this bioassay, technical-grade aldicarb
      was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

PMID- 12799657
TI  - Bioassay of malaoxon for possible carcinogenicity.
AB  - A bioassay of malaoxon, the oxygen analogue of malathion (an organophosphate
      insecticide), for possible carcinogenicity was conducted by administering the
      test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice
      of each sex were fed diets containing 500 or 1,000-ppm malaoxon for 103 weeks and
      were then observed for up to an additional 2 weeks. Matched controls consisted of
      groups of 50 untreated rats and 50 untreated mice of each sex. All surviving
      animals were killed at 103 to 105 weeks. The only effects that could be related
      to administration of malaoxon at the doses used were increased mortality among
      male mice, decreased mean body weights of female mice, gastric ulcers in male and
      female rats, and possibly C-cell adenomas or carcinomas of the thyroid among
      treated female rats. The incidence of C-cell adenomas or carcinomas among
      historical controls, however, precluded relating the incidence of these tumors to
      administration of the chemical. It was concluded that under the conditions of
      this bioassay malaoxon was not carcinogenic for F344 rats or B6C3F1 mice.

PMID- 12799658
TI  - Bioassay of C.I. vat yellow 4 for possible carcinogenicity.
AB  - A bioassay of C.I. vat yellow 4, a commercial formulation containing dibenzo(b,
      def) chrysene-7,14-dione, for possible carcinogenicity was conducted by
      administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
      Groups of 50 rats of each sex and 50 mice of each sex were administered C.I. vat
      yellow 4 in the diet at one of two doses, either 3,500 or 7,000 ppm for the rats,
      either 25,000 or 50,000 ppm for male mice, and either 12,500 or 25,000 ppm for
      the female mice. The rats were administered the test chemical for 104 weeks; the
      mice, for 106 weeks. Matched controls consisted of 20 untreated rats and 20
      untreated mice of each sex. All surviving animals were killed at the end of the
      period of administration of the test chemical. Mean body weights of the dosed
      rats were lower than those of corresponding controls throughout the bioassay, but
      the differences in weights were slight for the males. Mean body weights of the
      dosed mice were not affected by the test chemical. Survival of the rats and mice
      were not affected adversely by the chemical, and sufficient numbers of dosed and
      control rats and mice of each sex were at risk for the development of late
      appearing tumors. In the male and female rats and the female mice, no tumors
      occurred at incidences that were significantly higher in dosed groups than in
      control groups. In the male mice, lymphomas occurred at incidences that were dose
      related (P=0.002) and, in a direct comparison, the incidence of the tumor in the
      high-dose group was significantly higher (P=0.019) than that in the control group
      (controls 3/20, or 15%; low-dose 7/47, or 15%; high-dose 22/50, or 44%). The
      incidence of lymphomas and leukemias in historical-control male B6C3F1 mice, at
      this laboratory was 38/323 (12%). It is concluded that under the conditions of
      this bioassay, the formulated product containing C.I. vat yellow 4 was not
      carcinogenic for male or female Fischer 344 rats or for female B6C3F1 mice, but
      was carcinogenic for male B6C3F1 mice, causing an increased incidence of
      lymphomas.

PMID- 12799659
TI  - Bioassay of 3-nitro-p-acetophenetide for possible carcinogenicity.
AB  - A bioassay for possible carcinogenicity of 3-nitro-p-acetophenetide was conducted
      using Fischer 344 rats and B6C3F1 mice. 3-Nitro-p-acetophenetide was administered
      in the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species, with the exception of low dose male mice, of which there
      were 49. Fifty animals of each sex and species were placed on test as controls.
      The high and low time- weighted average dietary concentrations of 3-nitro-p
      acetophenetide were, respectively, 0.36 and 0.18 percent for rats and 1.46 and
      0.73 percent for mice. The compound was administered in the diet for 78 weeks,
      followed by an observation period of up to 30 weeks for rats and 20 weeks for
      mice. There were no significant positive associations between the concentrations
      of 3-nitro-p-acetophenetide administered and mortality in rats or mice of either
      sex. In addition, adequate numbers of animals in all groups survived sufficiently
      long to be at risk from late-developing tumors. There was a statistically
      significant increased incidence of a combination of hepatocellular carcinomas and
      adenomas when high dose male mice were compared to controls. No other neoplasm in
      any other dosed group occurred in significant positive increased incidences when
      compared to controls. Under the conditions of this bioassay, dietary
      administration of 3-nitro-p-acetophenetide was not carcinogenic in Fischer 344
      rats of either sex or in female mice. The compound, however, was considered
      carcinogenic in male B6C3F1 mice based on a significant increase in the combined
      incidence of hepatocellular carcinomas and hepatocellular adenomas in these
      animals.

PMID- 12799660
TI  - Bioassay of 2,5-dithiobiurea for possible carcinogenicity.
AB  - A bioassay of 2,5-dithiobiurea for possible carcinogenicity was conducted using
      Fischer 344 rats and B6C3F1 mice. 2,5-Dithiobiurea was administered in the feed,
      at either of two concentrations, to groups of 50 male and 50 female animals of
      each species, with the exception of high dose male rats, of which there were only
      49. The dietary concentrations used in the chronic bioassay were 0.6 percent for
      the low dose rats and 1.2 percent for the high dose rats. The dietary
      concentrations used for low and high dose mice were 1.0 and 2.0 percent,
      respectively. After a 78-week dosing period, observation of the mice continued
      for an additional 16 weeks. For each species, 50 animals of each sex were placed
      on test as controls. In both species, adequate numbers of animals in all groups
      survived sufficiently long to be at risk from late-developing tumors. Compound
      related mean body weight depression was observed in mice but not in rats. No
      consistent pattern of clinical signs was observed in either species. No tumors
      occurred at a significantly higher incidence in dosed rats than in their
      controls. Among female mice, the Cochran-Armitage test indicated a significant
      positive association between the incidence of hepatocellular carcinoma and
      dietary concentrations of 2,5-dithiobiurea. According to results of the Fisher
      exact test, the incidence of hepatocellular carcinoma was significantly higher in
      the high dose female mouse group when compared to the corresponding control group
      but not when compared to the laboratory historical control data. No neoplasms
      occurred at a significantly higher incidence in dosed male mice than in their
      controls. Under the conditions of this bioassay, the evidence suggested, but was
      insufficient to establish the carcinogenicity of 2,5-dithiobiurea for female
      B6C3F1 mice. The compound was not carcinogenic to male B6C3F1 mice or to male or
      female Fischer 344 rats.

PMID- 12799661
TI  - Bioassays of DDT, TDE, and p,p'-DDE for possible carcinogenicity.
AB  - Bioassays of technical-grade DDT, TDE, and p,p'-DDE for possible carcinogenicity
      were conducted using Osborne-Mendel rats and B6C3F1 mice. Each compound was
      administered in the feed, at either of two concentrations, to groups of 50 male
      and 50 female animals of each species. Twenty animals of each species and sex
      were placed on test as controls for the bioassay of each compound. The time
      weighted average high and low dietary concentrations of DDT were, respectively,
      642 and 321 ppm for male rats, 420 and 210 ppm for female rats, 44 and 22 ppm for
      male mice, and 175 and 87 ppm for female mice. The time-weighted average high and
      low dietary concentrations of TDE were, respectively, 3,294 and 1,647 ppm for
      male rats, 1,700 and 850 ppm for female rats, and 822 and 411 ppm for male and
      female mice. The time-weighted average high and low dietary concentrations of DDE
      were, respectively, 839 and 437 ppm for male rats, 462 and 242 ppm for female
      rats, and 261 and 148 ppm for male and female mice. After the 78-week dosing
      period there was an additional observation period of up to 35 weeks for rats and
      15 weeks for mice. There were significant positive associations between increased
      chemical concentration and accelerated mortality in female mice dosed with DDT
      and in both sexes of rats and in female mice dosed with DDE. This association was
      not demonstrated in other groups. There was, however, poor survival among control
      and dosed male mice used in the bioassays of DDT and DDE. In all cases adequate
      numbers of animals in all groups survived sufficiently long to be at risk from
      late-developing tumors. When those male rats receiving TDE and their controls
      were combined within each group so that the numerators of the tumor incidences
      represented those animals with either a follicular-cell carcinoma or a follicular
      cell adenoma of the thyroid, the incidence in the low dose group was
      significantly higher than that in the controls. There was a significant positive
      association between the concentration of DDE administered and the incidences of
      hepatocellular carcinomas in male and female mice. Among dosed rats and mice no
      other neoplasms occurred in statistically significant incidences when compared to
      their respective control groups. Under the conditions of these bioassays there
      was no evidence for the carcinogenicity of DDT in Osborne-Mendel rats or B6C3F1
      mice, of TDE in female Osborne-Mendel rats or B6C3F1 mice of either sex, or of
      p,p'-DDE in Osborne-Mendel rats, although p,p'-DDE was hepatotoxic in Osborne
      Mendel rats. The findings suggest a possible carcinogenic effect of TDE in male
      Osborne-Mendel rats, based on the induction of combined follicular-cell
      carcinomas and follicular-cell adenomas of the thyroid. Because of the variation
      of these tumors in control male rats in this study, the evidence does not permit
      a more conclusive interpretation of these lesions. p,p'-DDE was carcinogenic in
      B6C3F1 mice, causing hepatocellular carcinomas in both sexes.

PMID- 12799662
TI  - Bioassay of aniline hydrochloride for possible carcinogenicity.
AB  - A bioassay of aniline hydrochloride for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. Aniline hydrochloride was administered in
      the feed, at either of two concentrations, to groups of 50 male and female
      animals of each species, with the exception of 49 female mice in the high dose
      group. The high and low dietary concentrations of aniline hydrochloride were,
      respectively, 0.6 and 0.3 percent for rats and 1.2 and 0.6 percent for mice.
      After a 103-week period of compound administration, observation of the rats and
      mice continued for up to an additional 5 weeks. For rats and mice, respectively,
      25 and 50 animals of each sex were placed on test as controls and fed only the
      basal diet. In male rats there were several types of mesenchymal tumors,
      primarily of the spleen, associated with administration of the compound.
      Hemangiosarcomas of the spleen and the combined incidence of fibrosarcomas and
      sarcomas NOS of the spleen were each statistically significant in male rats. The
      combined incidence of fibrosarcomas and sarcomas NOS of multiple body organs was
      also significant in male rats. The number of female rats having fibrosarcomas or
      sarcomas NOS of either the spleen alone or multiple organs of the body cavity was
      significantly associated with increased dietary concentration of aniline
      hydrochloride. This result was not supported by the Fischer exact tests, but
      because of the rarity of these tumors, the observed incidences (0/24 in the
      control group, 1/50 [2 percent] in the low dose group, 7/50 [14 percent] in the
      high dose group) were considered indicative of a compound-related carcinogenic
      effect. In mice of both sexes no tumors occurred in statistically significant
      increased incidences among dosed groups when compared to controls. Under the
      conditions of this bioassay, dietary administration of aniline hydrochloride was
      carcinogenic to male and female Fischer 344 rats, inducing hemangiosarcomas and a
      combination of fibrosarcomas and sarcomas NOS of the spleen and a combination of
      fibrosarcomas and sarcomas NOS of multiple body organs. There was no evidence of
      compound-induced carcinogenicity in B6C3F1 mice of either sex.

PMID- 12799663
TI  - Bioassay of trimethylthiourea for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of trimethylthiourea was conducted
      using Fischer 344 rats and B6C3F1 mice. A mixture containing 80 percent
      trimethylthiourea and 15 percent dimethylthiourea was administered in the feed,
      at either of two concentrations, to groups of 50 male and 50 female animals of
      each species. Twenty animals of each sex and species were placed on test as
      controls. The high and low dietary concentrations of trimethylthiourea were,
      respectively, 500 and 250 ppm for rats and 1,000 and 500 ppm for mice. The
      compound was administered in the diet for 77 weeks, followed by an observation
      period of 29 weeks for rats and 14 weeks for mice. There were no significant
      positive associations between the dosage of trimethylthiourea administered and
      mortality in rats or mice of either sex. Adequate numbers of animals in all
      groups survived sufficiently long to be at risk from late-developing tumors. For
      high dose female rats and for dosed mice of both sexes, compound-related mean
      body weight depression was observed, indicating that the dosages of
      trimethylthiourea administered to these animals may have approximated the maximum
      tolerated dosages. Since no mean body weight depression relative to controls, no
      significant accelerated mortality, and no other signs of toxicity were associated
      with administration of trimethylthiourea to male rats, it is possible that these
      animals may have been able to tolerate a higher dietary concentration. The
      incidences of follicular-cell carcinomas of the thyroid in female rats were dose
      related, and there was a significant difference between the incidences in the
      high dose and control. This same relationship was established for the combination
      of follicular-cell carcinomas and follicular-cell adenomas in female rats. Under
      the conditions of this bioassay, dietary administration of trimethylthiourea was
      carcinogenic in female Fischer 344 rats, inducing follicular-cell carcinomas of
      the thyroid. There was not sufficient evidence for the carcinogenicity of the
      compound in male Fischer 344 rats or in B6C3F1 mice of either sex.

PMID- 12799664
TI  - Bioassay of 3,3'-dimethoxybenzidine-4,4'-diisocyanate for possible
      carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of 3,3'-dimethoxybenzidine-4,4'
      diisocyanate was conducted using Fischer 344 rats and B6C3F1 mice. 3,3'
      Dimethoxybenzidine-4,4'-diisocyanate was administered, at either of two
      concentrations, to groups of 50 male and 50 female animals of each species, with
      the exception of 49 high dose female rats. The compound was administered in the
      feed with the exception of the first 22 weeks of the rat bioassay, when it was
      administered by gavage. Twenty animals of each sex and species were placed on
      test as controls. During intubation the high and low dosages were 3,000 and 1,500
      mg/kg, respectively, while the high and low concentrations administered in the
      feed to both rats and mice were 44,000 and 22,000 ppm, respectively. The compound
      was administered for a period of 78 weeks, followed by an observation period of
      26 weeks for rats and 25 weeks for mice. There was a significant positive
      association between the administration of 3,3'-dimethoxybenzidine- 4,4'
      diisocyanate and mortality in male and female rats, but not in male or female
      mice. Adequate numbers of animals in all groups survived sufficiently long to be
      at risk from late-developing tumors. For both sexes of rats, there was a
      significant positive association between dosage and the incidence of leukemia and
      malignant lymphoma. There was a significantly higher incidence of neoplasms of
      the skin, excluding skin of the ear, when dosed male rats were compared to
      controls. There was a significant positive association between the dosages
      administered and the incidences of endometrial stromal polyps in female rats.
      None of the statistical tests for any site in male and female mice indicated a
      significant positive association between compound administration and tumor
      incidence. Under the conditions of this bioassay, administration of 3,3'
      dimethoxybenzidine-4,4'-diisocyanate was carcinogenic to Fischer 344 rats,
      causing neoplasms of the skin (excluding skin of the ear) in males, endometrial
      stromal polyps in females, and leukemia and malignant lymphoma in both sexes. The
      compound was also associated with the development of a combination of squamous
      cell carcinomas and sebaceous adenocarcinomas of the Zymbal's gland and skin of
      the ear in rats of both sexes. There was no evidence of the carcinogenicity of
      the compound in B6C3F1 mice.

PMID- 12799665
TI  - Bioassay of 5-nitro-o-anisidine for possible carcinogenicity.
AB  - A bioassay of 5-nitro-o-anisidine for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-anisidine was administered in
      the feed at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The dietary concentrations used in the chronic bioassay
      for low and high dose rats were 0.4 and 0.8 percent, respectively. Dose A and B
      mice were fed dietary concentrations of 0.8 and 1.6 percent when initially placed
      on test, but after week 15 the concentration fed to dose B mice was reduced to
      0.4 percent. After a 78-week period of chemical administration, observation of
      rats continued for up to an additional 28 weeks and observation of mice continued
      for up to an additional 19 weeks. For each species, 50 animals of each sex were
      placed on test as controls for the group receiving the higher concentration and
      49 to 50 animals were of each sex were placed on test as controls for the group
      receiving the lower concentration. In both species, adequate numbers of animals
      in all groups survived long enough to be at risk from late-developing tumors.
      Feeding of 5-nitro-o-anisidine to rats was associated with increased incidences
      of tumors of the integumentary system. Basal-cell carcinomas, trichoepitheliomas,
      squamous-cell carcinomas and sebaceous adenocarcinomas each occurred in the skin
      of high dose male rats at statistically significant incidences. For both male and
      female rats, carcinomas (the combined incidence of sebaceous adenocarcinomas,
      ceruminous carcinomas and squamous-cell carcinomas) of the Zymbal's gland or the
      skin of the ear were significant in the high dose groups. In the clitoral gland
      of dosed female rats, the incidence of carcinomas and the incidence of adenomas
      were each significant. Among mice, the incidence of hepatocellular carcinoma was
      statistically significant for dose B females when compared to their appropriate
      controls. Under the conditions of this bioassay, dietary administration of 5
      nitro-o-anisidine was carcinogenic in Fischer 344 rats, causing tumors of the
      integumentary system in males and females and of the clitoral gland in females.
      The compound was also carcinogenic to female B6C3F1 mice, causing hepatocellular
      carcinomas.

PMID- 12799666
TI  - Bioassay of 2,5-toluenediamine sulfate for possible carcinogenicity.
AB  - A bioassay for possible carcinogenicity of 2,5-toluenediamine sulfate was
      conducted using Fischer 344 rats and B6C3F1 mice. 2,5-Toluenediamine sulfate was
      administered in the feed, at either of two concentrations, to groups of 50 males
      and 50 females of each species. The high and low time-weighted average
      concentrations of the compound were, respectively, 0.2 and 0.06 percent for rats
      and 0.1 and 0.6 percent for mice. Because compound administration to the high and
      low dose groups of each species was not begun simultaneously, each dosed group
      was assigned a control group. All control groups consisted of 50 animals, except
      for the high dose male and female rat control groups which were composed of 25
      animals. The dosing period was for 78 weeks, followed by an additional 28 to 31
      weeks of observation in rats and an additional 16 to 19 weeks in mice. There was
      no significant association between compound administration and accelerated
      mortality in either sex of either species. Adequate numbers of animals in all
      groups survived sufficiently long to be at risk from late-developing tumors. A
      statistically significant incidence of interstitial-cell neoplasms of the testis
      in dosed male rats was not considered attributable to administration of the
      compound since the spontaneous incidence of these neoplasms in male Fischer 344
      rats is both high and variable. No neoplasms were observed in female rats at
      statistically significant incidences. A statistically significant increase in
      lung tumors in high dose female mice was not considered convincing evidence of a
      compound-related carcinogenic effect because high dose male mice were received in
      separate shipments from their controls and housed in separate rooms from their
      controls. Under the conditions of this bioassay, sufficient evidence was not
      obtained to demonstrate the carcinogenicity of 2,5-toluenediamine sulfate in
      either Fischer 344 rats or B6C3F1 mice.

PMID- 12799667
TI  - Bioassay of dioxathion for possible carcinogenicity.
AB  - A bioassay for possible carcinogenicity of technical-grade dioxathion was
      conducted using Osborne-Mendel and B6C3F1 mice. Dioxathion was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The high and low time-weighted average concentrations
      were, respectively, 180 and 90 ppm for male rats and 90 and 45 ppm for female
      rats. The high and low time-weighted average concentrations for male mice were
      567 and 284 ppm, respectively, and for female mice were 935 and 467 ppm,
      respectively. After a 78-week period of chemical administration, observation of
      the rats continued for an additional 33 weeks and the mice were observed for an
      additional 12 to 13 weeks. For rats, 50 animals of each sex were placed on test
      as controls and fed only the basal diet, while for mice, 20 animals of each sex
      served as controls. In both species adequate numbers of animals survived long
      enough to be at risk from late-appearing tumors. A variety of neoplasms was
      observed in treated animals of both species; however, none of the neoplasms
      observed were either histopathologically unusual or in statistically significant
      incidences. Under the conditions of this bioassay, dietary administration of
      dioxathion was not carcinogenic in Osborne-Mendel rats or B6C3F1 mice.

PMID- 12799668
TI  - Bioassay of piperonyl sulfoxide for possible carcinogenicity (CAS No. 120-62-7).
AB  - A bioassay of technical-grade piperonyl sulfoxide for possible carcinogenicity
      was conducted by administering the test chemical in feed to Fischer 344 rats and
      B6C3F1 mice. Groups of 50 rats of each sex were administered piperonyl sulfoxide
      in the diet at one of several doses, either 1,500 or 3,000 ppm for the males and
      either 3,000 or 6,000 ppm for the females, for 105 weeks. Matched controls
      consisted of 20 untreated rats of each sex. All surviving rats were killed at the
      end of the period of administration of the test chemical. Groups of 50 male mice
      were administered one of two doses, either 350 or 700 ppm, for 104 or 105 weeks.
      Groups of 50 female mice were initially administered one of two doses, either 700
      or 1,400 ppm. Due to excessive weight depression in the dosed female mice, the
      doses for this sex were reduced after week 20 to 200 and 600 ppm, respectively,
      and administration of the test chemical at the lower doses was continued for 84
      or 85 weeks. The time-weighted average doses for the females were 295 and 754
      ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving
      mice were killed at the end of the period of administration of the test chemical.
      Mean body weights of dosed groups of rats and mice of each sex were lower than
      those of corresponding control groups, and the depressions in the amount of mean
      body weight gained were dose related for most or all of the bioassay; the
      depression in the amount of mean body weight gained was slight, however, in the
      dosed male rats. Survival of the rats and mice was unaffected by the piperonyl
      sulfoxide and was 78% or higher in all groups at week 90 of the bioassay; thus
      sufficient numbers of dosed and control rats and mice of each sex were at risk
      for the development of late-appearing tumors. In the male and female rats and in
      the female mice, no tumors occurred at incidences that were significantly higher
      in dosed groups than in control groups. In the male mice, hepatocellular
      carcinomas occurred at incidences that were dose related (P<0.001); in direct
      comparisons, the incidence of these tumors in the high-dose group was
      significantly higher (P<0.001) than that in the control group (controls 6/18, low
      dose 31/50, high-dose 46/50). It is concluded that under the conditions of this
      bioassay, technical-grade piperonyl sulfoxide was not carcinogenic for male or
      female Fischer 344 rats or for female B6C3F1 mice, but was carcinogenic for male
      B6C3F1 mice, producing an increased incidence of hepatocellular carcinomas.

PMID- 12799669
TI  - Bioassay of 2,7-dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity.
AB  - A bioassay of 2,7-dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity
      was conducted by administering the test chemical in feed to Osborne-Mendel rats
      and B6C3F1 mice. Groups of 35 rats of each sex were administered DCDD at one of
      two doses, either 5,000 or 10,000 ppm, for 110 weeks. Groups of 50 mice of each
      sex were administered these same doses for 90 weeks. Controls consisted of 35
      untreated rats of each sex and 50 untreated mice of each sex. All surviving male
      rats were killed at 110 to 112 weeks, all surviving female rats at 110 to 117
      weeks, all surviving male mice at 92 to 101 weeks, and all surviving female mice
      at 91 to 98 weeks. Mean body weights of most of the dosed groups of rats and mice
      were lower than those of corresponding controls both when placed on study and for
      much of the study period; however, survival of any group was not significantly
      affected by administration of the test chemical. Sufficient numbers of dosed and
      control rats and mice of each sex were at risk for the development of late
      appearing tumors. No tumors were induced in male or female rats or female mice at
      incidences that were significantly higher in the dosed groups than in the
      corresponding control groups. Both low-and high-dose rats had toxic hepatic
      lesions characterized by centrilobular fatty metamorphosis and/or necrosis. In
      the male mice, hepatocellular adenomas or carcinomas occurred at incidences that
      were dose related (P=0.008), and, in direct comparisons, were higher in the low
      dose group (P=0.008) and the high-dose group (P=0.010) than in the control group
      (controls 8/49, low-dose 20/50, high-dose 17/42). However, the historical
      incidence of this lesion in control male B6C3F1 mice at this laboratory does not
      permit a clear association of the lesion with the administration of the test
      compound. There were also significant increases in the incidence of combinations
      of leukemias and lymphomas and of hemangiosarcomas and hemangiomas in the low
      dose male mice, but these findings were not supported by the high-dose animals.
      It is concluded that under the conditions of this bioassay, DCDD was not
      carcinogenic for Osborne-Mendel rats of either sex or for female B6C3F1 mice. The
      marginal increased incidences of combinations of leukemias and lymphomas, of
      hemangiosarcomas and hemangiomas, and of hepatocellular carcinomas and adenomas
      in male B6C3F1 mice are, however, considered as suggestive of a carcinogenic
      effect of 2,7-dichlorodibenzo-p-dioxin in these animals.

PMID- 12799670
TI  - Bioassay of dibenzo-p-dioxin for possible carcinogenicity.
AB  - A bioassay of dibenzo-p-dioxin (UDD) for possible carcinogenicity was conducted
      by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1
      mice. Groups of 35 rats of each sex were administered UDD at one of two doses,
      either 5,000 or 10,000 ppm, for 110 weeks. Groups of 50 mice of each sex were
      administered the same doses for 87 or 90 weeks. Controls consisted of groups of
      35 untreated rats of each sex and 50 untreated mice of each sex. All surviving
      male rats were killed at 110 weeks, all surviving male mice at 92 to 97 weeks,
      and all surviving female mice at 91 to 93 weeks. Mean body weights of the dosed
      male and female rats and mice were lower than those of the corresponding
      controls; the depression in the amount of weight gained in the dosed male mice
      was, however, relatively slight. Except for the male rats, survival at the end of
      the bioassay was lower in the dosed groups of both rats or mice than in the
      corresponding control groups. At week 90, at least 57% of the rats and 54% of the
      mice were still alive. Because the mean body weights and survival rates of the
      dosed animals were lower than those of corresponding controls and because there
      was an increase in the incidence of hepatotoxic lesions, the 10,000-ppm
      concentration administered to the rats and mice is considered to be the maximum
      tolerated dose. No tumors were induced in rats or mice of either sex at
      incidences that were significantly higher in the dosed groups than in the
      corresponding control groups. It is concluded that under the conditions of this
      bioassay, UDD was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.

PMID- 12799671
TI  - Bioassay of dimethyl terephthalate for possible carcinogenicity.
AB  - A bioassay of dimethyl terephthalate for possible carcinogenicity was conducted
      by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups
      of 50 rats of each sex and 50 mice of each sex were administered dimethyl
      terephthalate at one of two doses, either 2,500 or 5,000 ppm, for 103 weeks, then
      observed for 2 additional weeks. Matched controls consisted of 50 untreated rats
      of each sex and 50 untreated mice of each sex. All surviving rats were killed at
      105 or 106 weeks and all surviving mice at 104 or 105 weeks. Administration of
      dimethyl terephthalate had no appreciable effect on the mean body weights of the
      rats and mice of either sex. No clinical signs related to administration of the
      test chemical were noted in the rats. Survivals of the rats and mice at the end
      of the bioassay were not affected by the test chemical. Both species may have
      been able to tolerate higher doses. In rats and mice of each sex, no tumors
      occurred at incidences that clearly were related to administration of the test
      chemical. Although it is recognized that both rats and mice may not have received
      a dose of the test chemical sufficiently high to provide maximum test
      sensitivity, it is concluded that under the conditions of this bioassay, dimethyl
      terephthalate was not carcinogenic for F344 rats or B6C3F1 mice.

PMID- 12799672
TI  - Bioassay of piperonyl butoxide for possible carcinogenicity (CAS No. 51-03-6).
AB  - A bioassay of technical-grade piperonyl butoxide for possible carcinogenicity was
      conducted by administering the test chemical in feed to Fischer 344 rats and
      B6C3F1 mice. Groups of 50 rats of each sex were administered piperonyl butoxide
      in the diet at one of two doses, either 5,000 or 10,000 ppm, for 107 weeks.
      Matched controls consisted of 20 untreated rats of each sex. All surviving rats
      were killed at the end of the period of administration of the test chemical.
      Groups of 50 mice of each sex were initially administered piperonyl butoxide at
      one of two doses, either 2,500 or 5,000 ppm. After week 30, the doses for the
      mice were reduced to 500 and 2,000 ppm, respectively, and administration of the
      test chemical at the lowered doses was continued for 82 weeks. The time-weighted
      average doses for the mice were either 1,036 or 2,804 ppm. Matched controls
      consisted of 20 untreated mice of each sex. All surviving mice were killed at the
      end of the period of administration of the test chemical. Mean body weights of
      dosed groups of rats and mice of each sex were lower than those of corresponding
      control groups, and the depressions in body weights were dose related. Survival
      of the rats and mice was unaffected by the piperonyl butoxide and was 80% or
      greater in all groups at week 90 of the bioassay; thus, sufficient numbers of
      dosed and control rats and mice of each sex were at risk for the development of
      late-appearing tumors. In female rats, lymphomas occurred at incidences that were
      dose related (P=0.007); in a direct comparison, the incidence of the tumor in the
      high-dose group was higher (P=0.020) than that in the control group (controls
      1/20, low-dose 7/50, high-dose 15/50). However, the incidence of lymphomas,
      leukemias, and reticuloses in historical-control female Fischer 344 rats at the
      same laboratory was 19/191 (10%). These historical-control groups include one
      with an incidence of animals with lymphoma or leukemia of 7/20 (35%) and another
      with an incidence of 6/20 (30%). Thus, the incidence of lymphomas in the control
      female rats of the present bioassay may have been abnormally low, and the
      occurrence of the higher incidence in the dosed groups cannot be clearly related
      to administration of piperonyl butoxide. In the male mice, adenomas of the
      lacrimal gland occurred at incidences that were dose related (P=0.023), but in
      direct comparisons the incidences in the individual dosed groups were not
      significantly higher than that in the control group (controls 0/20, low-dose
      0/49, high-dose 4/50); thus, the occurrence of this tumor in the male mice was
      not clearly related to administration of the test chemical. It is concluded that
      under the conditions of this bioassay, piperonyl butoxide was not carcinogenic
      for Fischer 344 rats or B6C3F1 mice.

PMID- 12799673
TI  - Bioassay of 5-nitroacenaphthene for possible carcinogenicity (CAS No. 602-87-9).
AB  - A bioassay of 5-nitroacenaphthene for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 5-Nitroacenaphthene was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. For male and female rats, the high and low dietary
      concentrations of 5-nitroacenaphthene were 0.24 and 0.12 percent, respectively.
      The high and low time-weighted average concentrations for mice were 0.12 and 0.06
      percent, respectively, for males and 0.12 and 0.05 percent, respectively, for
      females. After a 78-week dosing period, observation of surviving rats continued
      for up to 22 weeks and observation of the mice continued for 18 weeks. For the
      chronic rat bioassay, 49 male and 50 female rats were placed on test as high dose
      controls, and 50 rats of each sex served as low dose controls. For the mice, 50
      males and 50 females were placed on test as controls. Accelerated mortality was
      observed in all dosed groups except the low dose female mice. There was a
      positive association between mortality and dietary concentration of 5
      nitroacenaphthene for both sexes of both species. Early deaths were most apparent
      among high dose male mice; half of the animals in this group were dead by week 20
      and insufficient male mice survived to be at risk from late-developing tumors.
      Among rats, the incidence of malignant tumors of the ear canal (incidences of
      ceruminous carcinomas and squamous-cell carcinomas were combined) was significant
      at each dose level in each sex. Among both dosed groups of female rats, the
      incidence of clitoral gland carcinoma and the incidence of mammary adenocarcinoma
      were significant. A significant incidence of alveolar/bronchiolar carcinoma was
      observed in low dose rat groups of each sex. Among female mice, the incidence of
      hepatocellular carcinoma was significant at each dose level. The combined
      incidence of granulosa-cell tumors, luteomas, and tubular-cell adenomas of the
      ovary was significant in the high dose female mouse group. Under the conditions
      of this bioassay, 5-nitroacenaphthene was carcinogenic to Fischer 344 rats,
      causing increased incidences of malignant tumors of the ear canal and lung in
      both sexes, and of the clitoral gland and mammary gland in females. 5
      Nitroacenaphthene was also carcinogenic to female but not male B6C3F1, mice,
      causing carcinomas of the liver and ovarian tumors.

PMID- 12799674
TI  - Bioassay of 6-nitrobenzimidazole for possible carcinogenicity (CAS No. 94-52-0).
AB  - A bioassay for possible carcinogenicity of 6-nitrobenzimidazole was conducted
      using Fischer 344 rats and B6C3F1 mice. 6-Nitrobenzimidazole was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The dietary concentrations used in the chronic bioassay
      were 0.5 and 0.12 percent for the high and low dose rats, respectively, and 0.24
      and 0.12 percent for the high and low dose mice, respectively. After a 78-week
      period of compound administration, observation of the rats continued for up to an
      additional 29 weeks and observation of the mice continued for an additional 18
      weeks. For each species and each dosed group, 49 or 50 animals of each sex were
      placed on test as controls. There were no significant positive associations
      between the administered dietary concentrations of 6-nitrobenzimidazole and
      mortality in either sex of rats or mice. In all groups adequate numbers of
      animals survived sufficiently long to be at risk from late-developing tumors.
      Among both male and female mice, the incidences of hepatocellular carcinomas in
      high dose groups were statistically significant relative to controls. Among rats
      of both sexes, nonneoplastic lesions of the eyes and of the Harderian glands
      appeared to be associated with administration of 6-nitrobenzimidazole. No
      neoplasms, however, were attributed to compound administration. Under the
      conditions of this bioassay, dietary administration of 6-nitrobenzimidazole was
      not carcinogenic to Fischer 344 rats; however, the compound was carcinogenic to
      B6C3F1 mice, causing hepatocellular carcinomas in both sexes.

PMID- 12799675
TI  - Bioassay of p-Anisidine Hydrochloride for Possible Carcinogenicity (CAS No. 20265
      97-8).
AB  - A bioassay for possible carcinogenicity of p-anisidine hydrochloride was
      conducted using Fischer 344 rats and B6C3F1 mice. p-Anisidine hydrochloride was
      administered in the feed, at either of two concentrations, to groups of 55 male
      and 55 female animals of each species. Fifty-five animals of each sex and species
      were placed on test as controls. The high and low dietary concentrations of p
      anisidine hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.0
      and 0.5 percent for mice. The compound was administered in the diet for 103
      weeks, followed by an observation period of 2 to 3 weeks for rats and 2 weeks for
      mice. There were no significant positive associations for either species between
      the concentration of p-anisidine hydrochloride administered and mortality. In
      addition, adequate numbers of animals in all groups survived sufficiently long to
      be at risk from late-developing tumors. In male rats there were significant
      associations between compound administration and the incidences of both squamous
      cell carcinomas of the skin and alveolar/bronchiolar adenomas. None of the
      Fischer exact comparisons, however, supported these findings. When those males
      having adenomas NOS or carcinomas NOS of the preputial gland were combined and
      the resulting incidences statistically analyzed, the only test providing a
      significant result was the Fisher exact comparison of the low dose to the
      control. There were no significant positive associations between the
      administration of p-anisidine hydrochloride and the incidence of any tumor in
      mice of either sex. Although, under the conditions of this bioassay, there
      appeared to be an association between chemical administration and the increased
      incidence of preputial gland tumors in low dose male rats, the evidence was
      insufficient to establish the carcinogenicity of p-anisidine hydrochloride in
      Fischer 344 rats. The compound was not carcinogenic in B6C3F1 mice.

PMID- 12799676
TI  - Bioassay of sulfallate for possible carcinogenicity (CAS No. 95-06-7).
AB  - A bioassay for possible carcinogenicity of sulfallate was conducted using Osborne
      Mendel rats and B6C3F1 mice. Sulfallate was administered in the feed, at either
      of two concentrations, to groups of 50 male and 50 female animals of each
      species. Twenty mice and 50 rats of each sex were placed on test as controls for
      the bioassay. The time-weighted average high and low dietary concentrations of
      sulfallate were, respectively, 410 and 250 ppm for male rats, 404 and 250 ppm for
      female rats, 1,897 and 949 ppm for male mice, and 1,815 and 908 ppm for female
      mice. After a 78-week period of chemical administration, there was an additional
      observation period of 25 to 26 weeks for dosed rats, 33 weeks for control rats,
      and 12 to 13 weeks for dosed and control mice. There were significant positive
      associations between increased sulfallate concentration and accelerated mortality
      in both sexes of rats and in female mice. However, adequate numbers of animals in
      all groups survived sufficiently long to be at risk from late-developing tumors.
      Statistical analyses of the incidences of mammary adenocarcinomas in female rats,
      stomach neoplasms (i.e.,combination of papillomas NOS, squamous-cell papillomas,
      and squamous-cell carcinomas) in male rats, combined alveolar/bronchiolar
      carcinomas and alveolar/bronchiolar adenomas in male mice, and adenocarcinomas of
      the mammary gland in female mice revealed a significant positive association
      between dosage and incidence. These associations were all supported by at least
      one significant Fisher exact comparison. The incidences of toxic tubular
      nephropathy observed in male rats and in mice of both sexes increased with the
      concentration of the compound administered. This nonneoplastic lesion was not
      observed in control animals. Under the conditions of this bioassay, dietary
      administration of sulfallate was carcinogenic to Osborne-Mendel rats and to
      B6C3F1 mice, inducing mammary gland tumors in females of both species, tumors of
      the forestomach in male rats, and lung tumors in male mice.

PMID- 12799677
TI  - Bioassay of 2,3,5,6-tetrachloro-4-nitroanisole for possible carcinogenicity (CAS
      No. 2438-88-2).
AB  - A bioassay for possible carcinogenicity of 2,4,5,6-tetrachloro-4-nitroanisole was
      conducted using Fischer 344 rats and B6C3F1 mice. 2,3,5,6-Tetrachloro-4
      nitroanisole was administered in the feed, at either of two concentrations, to
      groups of male and female animals of each species. The high and low dietary
      concentrations used in the chronic bioassay were 0.012 and 0.006 percent,
      respectively, for both species. After a 104-week period of chemical
      administration, observation of rats continued for up to 3 weeks and observation
      of mice continued for up to 1 week. For rats 50 animals of each sex were placed
      on test as controls, while for mice 55 animals of each sex were placed on test as
      controls. There were no significant positive associations between the dietary
      concentration of 2,3,5,6-tetrachloro-4-nitroanisole administered and mortality in
      rats or mice of either sex. Adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. No neoplasms, except
      for interstitial-cell testicular tumors in males, occurred at statistically
      significant incidences in dosed rats. Because of the high and variable
      spontaneous incidence of these lesions in Fischer 344 rats, these tumors were not
      considered to be associated with the administration of the test compound. Among
      dosed male mice the combined incidence of leukemia and malignant lymphoma was
      statistically significant. However, since these lesions were not spontaneously
      and with high variation in B6C3F1 mice, the lesions were not considered to be
      associated with the administration of the test compound. No neoplasms were of a
      statistically significant incidence in dosed female mice. Under the conditions of
      this bioassay, dietary administration of 2,3,5,6-tetrachloro-4-nitroanisole was
      not carcinogenic to male or female Fischer 344 rats or B6C3F1 mice of either sex.

PMID- 12799678
TI  - Bioassay of 2-chloro-p-phenylenediamine sulfate for possible carcinogenicity (CAS
      No. 61702-44-1).
AB  - A bioassay for possible carcinogenicity of 2-chloro-p-phenylenediamine sulfate
      was conducted using Fischer 344 rats and B6C3F1 mice. 2-Chloro-p-phenylenediamine
      sulfate was administered in the feed, at either of two concentrations, to groups
      of 50 male and 50 female animals of each species. The dietary concentrations used
      in the chronic bioassay were 0.3 and 0.15 percent for the high and low dose rats,
      respectively, and 0.6 and 0.3 percent for the high and low dose mice,
      respectively. Compound administration was for 105 to 107 weeks in rats, 87 weeks
      in high dose mice, and 104 to 105 weeks in low dose mice. The only groups
      observed during an untreated period after dosing were the high dose mice,
      observed for 18 weeks after compound administration ceased. For each species, 20
      animals of each sex were placed on test as controls. There were no significant
      positive associations between the administered dietary concentrations of 2-chloro
      p-phenylenediamine sulfate and mortality for rats of either sex or male mice.
      There was a significant positive association between dosage and mortality for
      female mice; however, adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. There were no
      statistically significant positive associations between dietary exposure to the
      compound and the incidences of any tumor in rats. There was an increased
      incidence of transitional-cell hyperplasia of the renal pelvic epithelium in both
      male and female rats, and transitional-cell tumors of the urinary bladder were
      present in three dosed rats. These lesions indicated a possible carcinogenic
      effect, but are not considered as sufficient evidence of carcinogenicity. In
      mice, no tumors occurred in statistically significantly higher incidences in the
      dosed mice than in controls. Under the conditions of this bioassay there was
      insufficient evidence that dietary administration of 2-chloro-p-phenylenediamine
      sulfate was carcinogenic to Fischer 344 rats and B6C3F1 mice.

PMID- 12799679
TI  - Bioassay of 3-amino-4-ethoxyacetanilide for possible carcinogenicity (CAS No.
      17026-81-2).
AB  - A bioassay of 3-amino-4-ethoxyacetanilide for possible carcinogenicity was
      conducted using Fischer 344 rats and B6C3F1 mice. 3-Amino-4-ethoxyacetanilide was
      administered in the feed, at either of two concentrations, to groups of
      approximately 50 male and 50 female animals of each species. The dietary
      concentrations used in the chronic bioassay for low and high dose rats were 0.4
      and 1.5 percent, respectively. The dietary concentrations used for low and high
      dose mice were 0.4 and 0.8 percent, respectively. After a 78-week period of
      chemical administration, observation of rats continued for up to 18 weeks. For
      each species, 50 animals of each sex were placed on test as controls for low dose
      groups and approximately 50 animals of each sex were placed on test as controls
      for high dose groups. In both species, adequate numbers of animals in all groups
      survived sufficiently long enough to be at risk from late-developing tumors.
      Among rats the only clearly compound-related lesion was hemosiderosis of the
      thyroid gland. No neoplastic lesions were statistically significant in dosed
      rats. Among mice the incidence of follicular-cell carcinomas of the thyroid gland
      was significant for high dose males. An elevated incidence of thyroid hyperplasia
      was observed in each dosed group. Hemosiderosis of the thyroid cells were found
      in nearly all dosed mice, but not in any control mice. Under the conditions of
      this bioassay, 3-amino-4-ethoxyacetanilide was carcinogenic in male B6C3F1 mice,
      causing follicular-cell carcinomas of the thyroid gland. Evidence provided by
      this bioassay was insufficient to establish the carcinogenicity of 3-amino-4
      ethoxyacetanilide in female mice or in Fischer 344 rats of either sex.

PMID- 12799680
TI  - Bioassay of 1-amino-2-methylanthraquinone for possible carcinogenicity (CAS No.
      82-28-0).
AB  - A bioassay for possible carcinogenicity of technical-grade 1-amino-2
      methylanthraquinone was conducted using Fischer 344 rats and B6C3F1 mice. 1-Amino
      2-methylanthraquinone was administered in the feed, at either of two
      concentrations, to groups of 45 to 50 males and females of each species. The high
      and low time-weighted average concentrations of 1-amino-2-methylanthraquinone
      were 0.20 and 0.10 percent, respectively, for male and female rats. For mice, two
      dosage regimens (designated A and B) were used, but the time-weighted average
      concentrations were the same, 0.06 percent. For each species, 50 animals of each
      sex were placed on test as controls. The period of compound administration was 78
      weeks for rats followed by 26 to 28 additional weeks of observation, and 73 weeks
      for mice followed by 24 to 25 additional weeks of observation. A statistically
      significant positive association between compound administration and mortality
      was established for the male and female dose A mice. Dose A mice did not survive
      sufficiently long to be at risk from late-developing tumors. Survival in all
      other groups was adequate. The incidence of hepatocellular carcinomas was
      statistically significant among dosed rats of both sexes. Kidney neoplasms (the
      combined incidence of tubular-celladenomas, tubular-cell adenocarcinomas, and
      adenocarcinomas NOS) were significantly increased among dosed male rats.
      Administration of the compound was associated with a significant increase in the
      combined incidence of hepatocellular carcinomas and neoplastic liver nodules in
      female mice. No other neoplasms occurred in statistically significant positive
      incidences in male or female mice. 1-Amino-2-methylanthraquinone demonstrated
      nephrotoxic properties in mice of both sexes. Under the conditions of this
      bioassay, 1-amino-2-methylanthraquinone was carcinogenic in Fischer 344 rats,
      inducing hepatocellular carcinomas in rats of both sexes, and kidney tumors in
      male rats. The compound was carcinogenic in female B6C3F1 mice, producing an
      increased combined incidence of hepatocellular carcinomas and neoplastic nodules.

PMID- 12799681
TI  - Bioassay of iodoform for possible carcinogenicity (CAS No. 75-47-8).
AB  - A bioassay for possible carcinogenicity of technical-grade iodoform was conducted
      using Osborne-Mendel rats and B6C3F1 mice. Iodoform in corn oil was administered
      by gavage, at either of two dosages, to groups of 50 male and 50 female animals
      of each species. Administration of the chemical occurred 5 days per week, for a
      period of 78 weeks, followed by an observation period of 34 weeks for rats and 13
      or 14 weeks for mice. The high and low time-weighted average dosages of iodoform
      were, respectively, 142 and 71 mg/kg/day for male rats, 55 and 27 mg/kg/day for
      female rats, and 93 and 47 mg/kg/day for male and female mice. For each species,
      20 animals of each sex were placed on test as vehicle controls. These animals
      were gavaged with pure corn oil at the same rate as the high dose group of the
      same sex. Twenty animals of each sex were placed on test as untreated controls
      for each species. These animals were not intubated. A significant positive
      association between dosage and mortality was observed in male rats but not in
      female rats or in mice of either sex. Adequate numbers of animals in all groups
      survived sufficiently long to be at risk from late-developing tumors. No
      statistical significance could be attributed to the incidences of any neoplasms
      in rats or mice of either sex when compared to their respective controls. Under
      the conditions of this bioassay, no convincing evidence was provided for the
      carcinogenicity of iodoform in Osborne-Mendel rats or B6C3F1 mice.

PMID- 12799682
TI  - Bioassay of 4-nitroanthranilic acid for possible carcinogenicity (CAS No. 619-17
      0).
AB  - A bioassay of 4-nitroanthranilic acid for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 4-Nitroanthranilic acid was administered
      in the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The high and low time-weighted average concentrations
      used for the chronic study were, respectively, 1.5 and 0.46 percent for rats and
      1.0 and 0.46 percent for mice. After a 78-week period of chemical administration,
      the rats were observed for an additional period of up to 32 weeks and the mice
      for an additional period of up to 17 weeks. For rats 50 animals of each sex were
      placed on test as low dose controls and 25 animals of each sex were placed on
      test as high dose controls. For mice 50 animals of each sex were placed on test
      as controls for each dose group. No statistically significant increases in tumor
      incidence were observed among rats or mice receiving diets containing 4
      nitroanthranilic acid. Under the conditions of this bioassay evidence was not
      provided for the carcinogenicity of 4-nitroanthranilic acid in Fischer 344 rats
      or B6C3F1 mice.

PMID- 12799683
TI  - 13-week subchronic toxicity studies of direct blue 6, direct black 38, and direct
      brown 95 dyes.
AB  - Thirteen-week subchronic toxicity studies of direct blue 6, direct black 38, and
      direct brown 95 dyes were conducted by administering the test chemicals in feed
      to Fischer 344 rats and B6C3F1 mice. Groups of 10 rats and 10 mice of each sex
      were administered one of the three dyes at one of five concentrations for 13
      weeks and then necropsied, beginning the second day after the end of the dosing
      period. The concentrations used for the rats were 190, 375, 750, 1,500, and 3,000
      ppm. The concentrations used for the mice were 750, 1,500, 3,000, 6,000, and
      12,500 ppm, except for the female mice administered direct brown 95 dye, which
      were given concentrations of 375, 750, 1,500, 3,000, and 6,000 ppm. Matched
      controls consisted of groups of 10 untreated rats and 10 untreated mice of each
      sex. Mean body weights of the male and female rats administered the two or three
      highest doses of any one of the test dyes were lower than mean body weights of
      the corresponding controls, and the depressions in mean body weight were dose
      related. Mean body weights of the male and female mice administered the highest
      dose of any one of the test dyes were slightly lower than mean body weights of
      the corresponding controls; mean body weights of mice administered lower doses
      were generally unaffected. All male and female rats administered 3,000 ppm of any
      one of the dyes or 1,500 ppm of direct brown 95 dye died before the end of the
      studies. One male administered 1,500 ppm direct blue 6 dye, six males
      administered 1,500 ppm direct black 38 dye, and two males administered 750 ppm
      direct brown 95 dye also died by the end of the studies. No deaths occurred in
      any other dosed group or in any control group of rats. All male and female mice
      administered the test dyes survived to the end of the studies, except for one
      male whose death was attributed to bacterial infection. Benzidine and monoacetyl
      benzidine were detected in the urine of male and female rats and mice
      administered the test dyes, but neither compound was detected in the urine of
      control rats and mice. Determinations of methemoglobin in control and dosed rats
      showed no differences. In rats, neoplastic lesions occurred only in dosed groups
      and consisted of hepatocellular carcinomas and neoplastic nodules of the liver.
      The incidences of hepatocellular carcinomas in female rats administered 3,000 ppm
      direct blue 6 dye (4/9) and male rats administered 1,500 ppm direct black 38 dye
      (4/9) were significant (P=0.033) when related to the incidences of the tumors in
      the corresponding controls (0/10); hepatocellular carcinomas were also observed
      in two male rats administered 1,500 ppm direct blue 6 dye and in one female rat
      administered 1,500 ppm direct brown 95 dye. No control rats from any of the three
      studies developed hepatocellular carcinomas. When incidences of neoplastic
      nodules were combined with those of hepatocellular carcinomas, the significance
      increased to P<0.001 for male rats administered 1,500 ppm direct blue 6 dye,
      P=0.001 for females administered 3,000 ppm direct blue 6 dye, P<0. 001 for males
      administered 1, 500 ppm direct black 38 dye, and P=0.007 for females administered
      1,500 ppm direct brown 95 dye. No controls developed neoplastic nodules. Female
      rats administered direct black 38 dye developed no hepatocellular carcinomas, but
      had an incidence of neoplastic nodules of 5/10, with a significance of P=0.016.
      Male rats administered direct brown 95 dye developed neither hepatocellular
      carcinomas nor neoplastic nodules, but as indicated below, had significant
      incidences of preneoplastic lesions. The failure of groups of rats administered
      3,000 ppm dye to develop tumors when other groups administered 1,500 ppm did
      develop tumors may be due to earlier deaths at the higher dose. Preneoplastic
      hepatic lesions (basophilic foci) occurred only in dosed rats and did not occur
      in the controls. The incidences of the basophilic foci were significant (P<0.033)
      in male (4/9) and female (7/9) rats administered 3,000 ppm direct blue 6 dye and
      in male rats (7/8) administered 1, 500 ppm direct brown 95 dye. Basophilic foci
      also occurred, at lower incidences, in males (1/10) administered 1,500 ppm direct
      blue 6 dye, in males (3/9) administered 1,500 ppm direct black 38 dye, in females
      (1/8) administered 3,000 ppm direct black 38 dye, in males administered 750 ppm
      (3/10) or 3,000 ppm (2/9) direct brown 95 dye, and in females administered 1,500
      ppm (3/8) or 3,000 ppm (3/8) direct brown 95 dye. When incidences of foci of
      cellular alteration, a possible preneoplastic lesion, were added to those of
      basophilic foci, significance occurred in additional dosed groups. In mice, no
      neoplastic lesions occurred in the liver or other tissues of groups administered
      the different dyes. However, three mice administered 12,500 ppm direct black 38
      dye and one mouse administered 12,500 ppm direct brown 95 dye had foci of
      cellular alteration, in which the cells were basophilic when compared with
      surrounding normal cells. It is concluded that under the conditions of these 13
      week subchronic toxicity studies, direct blue 6 and direct black 38 dyes were
      carcinogenic in male and female Fischer 344 rats and direct brown 95 was
      carcinogenic in female rats; all three dyes induced hepatocellular carcinomas and
      neoplastic nodules in the liver. The test dyes were not carcinogenic for B6C3F1
      mice in the 13-week subchronic toxicity studies.

PMID- 12799684
TI  - Bioassay of 5-nitro-o-toluidine for possible carcinogenicity (CAS No. 99-55-8).
AB  - A bioassay of 5-nitro-o-toluidine for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-toluidine was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The time-weighted average high and low dietary
      concentrations of 5-nitro-o-toluidine were, respectively, 0.01 and 0.005 percent
      for rats, and 0.23 and 0.12 percent for mice. After a 78-week period of compound
      administration, observation of the rats continued for an additional 30 to 31
      weeks and observation of the mice continued for up to an additional 20 weeks. For
      each species, 50 animals of each sex were placed on test as controls and fed only
      the basal diet. There were no significant positive associations between the
      concentration of 5-nitro-o-toluidine administered and mortality in rats or mice
      of either sex, and adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. No unusual tumors
      were observed in rats of either sex and no convincing statistical evidence was
      provided for a significant positive association between compound administration
      and the incidence of any neoplasm in rats. Among mice there was a statistically
      significant positive association between administration of the chemical and the
      incidences of hepatocellular carcinomas in both males and females. The combined
      incidence of hemangiomas and hemangiosarcomas in male mice and the incidence of
      hemangiosarcomas in female mice were not statistically significant in relation to
      their respective control groups. However, they were considered to be associated
      with compound administration since they rarely occur in untreated B6C3F1 mice.
      Under the conditions of this bioassay 5-nitro-o-toluidine was carcinogenic in
      B6C3F1 mice, causing hepatocellular carcinomas in both sexes, an increase in the
      combined incidence of hemangiomas and hemangiosarcomas in male mice, and an
      increased incidence of hemangiosarcomas in female mice. The compound was not
      carcinogenic in Fischer 344 rats.

PMID- 12799685
TI  - Bioassay of trichlorofluoromethane for possible carcinogenicity (CAS No. 75-69
      4).
AB  - The bioassay of technical-grade trichlorofluoromethane for possible
      carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice.
      Trichlorofluoromethane in corn oil was administered by gavage, at either of two
      dosages, to groups of 50 male and 50 female animals of each species, 5 days per
      week, over a period of 78 weeks. The time-weighted average high and low dosages
      of trichlorofluoromethane in the chronic bioassay were, respectively, 977 and 488
      mg/kg/day for male rats, 1,077 and 538 mg/kg/day for female rats, and 3,925 and
      1,962 mg/kg/day for mice of both sexes. After a 78-week dosing period, rats were
      observed for an additional period of up to 33 weeks and mice were observed for an
      additional period of up to 13 weeks. For each species, 20 animals of each sex
      were placed on test as vehicle controls. These animals were gavaged with corn oil
      at the same time that dosed animals were gavaged with trichlorofluoromethane.
      Twenty animals of each sex were placed on test as untreated controls for each
      species. These animals were not gavaged. A high rate of early deaths occurred
      among male and female rats in this bioassay. An insufficient number of rats of
      either sex survived long enough to be at risk from late-developing tumors.
      Survival of mice was adequate for meaningful statistical analysis of late
      developing tumors. Results of a time-adjusted statistical analysis of tumor
      incidence in rats indicated no significant positive associations between
      administration of trichlorofluoromethane and tumor incidence. No groups of male
      or female mice dosed with trichlorofluoromethane had significantly increased
      tumor incidences relative to their respective control groups. The results of the
      bioassay of trichlorofluoromethane in Osborne-Mendel rats for possible
      carcinogenicity are not conclusive because inadequate numbers of rats survived
      sufficiently long enough to be at risk from late-developing tumors. Under the
      conditions of this bioassay, trichlorofluoromethane was not carcinogenic to male
      or female B6C3F1 mice.

PMID- 12799686
TI  - Bioassay of m-Cresidine for possible carcinogenicity (CAS No. 102-50-1).
AB  - A bioassay of technical-grade m-cresidine for possible carcinogenicity was
      conducted using Fischer 344 rats and B6C3F1 mice. m-Cresidine in corn oil was
      administered by gavage five days a weeks at either of two dosages, to groups of
      50 male and 49 or 50 female animals of each species. The dosages used in the
      chronic bioassay for low and high dose rats were 0.08 and 0.16 gm/kg/day,
      respectively. The time-weighted average dosages used for low and high dose mice
      were 0.06 and 0.11 gm/kg/day, respectively. After a 77-week dosing period
      observation of rats continued for an additional 32 to 33 weeks. After a 53-week
      dosing period, observation of mice continued for an additional observation period
      of up to 41 weeks. For each species, 50 animals of each sex were placed on test
      as untreated controls and 25 animals of each sex were placed on test as vehicle
      controls. The urinary bladder and the kidney were the target organs of m
      cresidine toxicity in male and female rats. Papillary transitional-cell
      carcinomas of the urinary bladder occurred in 0/45 low dose males, 5/44 (11
      percent) high dose males, 1/46 (2 percent) low dose females, and 2/44 (5 percent)
      high dose females but did not occur in any untreated control or vehicle control
      rats. Although the incidences in each dosed rat group were not statistically
      significant when compared to vehicle controls, comparison with historical
      controls indicates that these bladder carcinomas are rare and are, therefore,
      considered to be compound-related in both sexes. Among mice, dose-related
      nonneoplastic lesions were observed at higher incidences for males than females
      in the kidneys, spleen and thymus. Dose-related toxic effects were also observed
      in testes of male mice. No neoplasms occurred in male mice at statistically
      significant incidences. Under the conditions of this bioassay, m-cresidine was
      carcinogenic to Fischer 344 rats, causing papillary transitional-cell carcinomas
      of the urinary bladder in both sexes. No convincing evidence was provided for
      carcinogenicity in female B6C3F1 mice. Poor survival of male B6C3F1 mice
      receiving m-cresidine precluded evaluation of the possible carcinogenicity of the
      compound in these animals.

PMID- 12799687
TI  - Bioassay of 4'-(chloroacetyl)-acetanilide for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was
      conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide
      was administered in the feed, at either of two concentrations, to groups of 50
      male and 50 female animals of each species. Twenty animals of each sex and
      species were placed on test as controls. The high and low dietary concentrations
      of 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats
      and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of
      a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice
      were killed at the end of the last week of compound administration, while rats
      were observed for 1 week after compound administration ceased. There were no
      significant positive associations between the concentration of 4'-(chloroacetyl)
      acetanilide administered and mortality in rats or mice of either sex. Adequate
      numbers of animals in all groups survived sufficiently long to be at risk from
      late-developing tumors. Dose-related mean body weight depression was observed for
      males and females of both species, indicating that the concentrations of 4'
      (chloroacetyl)-acetanilide administered to the animals in this bioassay may have
      approximated the maximum tolerated concentrations. None of the statistical tests
      for any site in rats of either sex or in male mice indicated a significant
      positive association between compound administration and tumor incidence.
      Although there was a significant positive association between the concentration
      of the compound administered and the incidences of hepatocellular adenomas in
      female mice, the Fischer exact comparisons were not significant. Under the
      conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic
      when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.

PMID- 12799688
TI  - Bioassay of lithocholic acid for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of lithocholic acid was conducted
      using Fischer 344 rats and B6C3F1 mice. Lithocholic acid was administered by
      gavage, at either of two dosages, to groups of 50 male and 50 female animals of
      each species, except for 49 low dose female rats. Twenty animals of each sex and
      species were placed on test as controls. The high and low dosages of lithocholic
      acid administered were, respectively, 500 and 250 mg/kg for rats and 250 and 125
      mg/kg for mice. The compound was administered to rats and mice for 103 weeks. The
      period of compound administration was followed by an observation period of 1 week
      for rats and 2 weeks for mice. There were no significant positive associations
      between the dosages of lithocholic acid administered and mortality in rats or
      mice of either sex. Adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. Slight dose-related
      mean body weight depression was observed in male rats and female mice and high
      incidences of chronic kidney inflammation were observed in female rats,
      indicating that the dosages of lithocholic acid administered to these animals in
      this bioassay may have approximated the maximum tolerated dosages. Since no mean
      body weight depression, relative to controls, no significant accelerated
      mortality, and no other signs of toxicity were associated with administration of
      lithocholic acid to male mice, it is possible that these animals may have been
      able to tolerate a higher dosage. However, in the subchronic study there were
      deaths among all dosed male mouse groups, even those receiving lithocholic acid
      at a level only twofold greater than the high dose utilized in the chronic study.
      None of the statistical tests for any site in rats or in mice of either sex
      indicated a significant positive association between compound administration and
      tumor incidence. Under the conditions of this bioassay, lithocholic acid was not
      carcinogenic when administered by gavage to Fischer 344 rats or B6C3F1 mice.

PMID- 12799689
TI  - Bioassay of p-phenylenediamine dihydrochloride for possible carcinogenicity.
AB  - A bioassay of p-phenylenediamine dihydrochloride for possible carcinogenicity was
      conducted using Fischer 344 rats and B6C3F1 mice. p-Phenylenediamine
      dihydrochloride was administered in the feed, at either of two concentrations, to
      groups of 50 male and 50 female animals of each species. The high and low
      concentrations of p-phenylenediamine dihydrochloride were, respectively, 1,250
      and 625 ppm for both rats and mice. After a 103-week period of compound
      administration, there were additional observation periods of 2 weeks for rats and
      1 week for mice. Twenty animals of each sex and species were placed on test as
      controls. There were no significant positive associations between the
      concentrations of p-phenylenediamine dihydrochloride administered and mortality
      in rats or mice of either sex. Adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late developing tumors. Slight dose-related
      mean body weight depression was observed in female rats and the mean body weights
      among high dose male rats and dosed female mice were slightly depressed in
      relation to their respective controls, indicating that the concentrations of p
      phenylenediamine dihydrochloride administered to these animals in this bioassay
      may have approximated the maximum tolerated concentrations. Since no distinct
      mean body weight depression relative to controls, no significant accelerated
      mortality, and no other signs of toxicity were associated with administration of
      p-phenylenediamine dihydrochloride to male mice, it is possible that these
      animals may have been able to tolerate a higher dietary concentration. None of
      the statistical tests for any site in rats or mice of either sex, including time
      to leukemia or malignant lymphoma analysis in female mice, indicated a
      significant positive association between compound administration and tumor
      incidence. Under the conditions of this bioassay, there was no convincing
      evidence that dietary administration of p-phenylenediamine dihydrochloride was
      carcinogenic in Fischer 344 rats or B6C3F1 mice.

PMID- 12799690
TI  - Bioassay of carbromal for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of carbromal was conducted using
      Fischer 344 rats and B6C3F1 mice. Carbromal was administered in the feed, at
      either of two concentrations, to groups of 50 male and 50 female animals of each
      species with the exception of 49 low dose male mice and high dose female mice.
      Twenty animals of each sex and species were placed on test as controls. The high
      and low dietary concentrations of carbromal were, respectively, 2,500 and 1,250
      ppm for rats and 2,500 and 1,250 ppm for mice. The compound was administered for
      103 weeks to rats and for 78 weeks to mice. The period of compound administration
      was followed by an observation period of 1 week for rats and 26 weeks for mice.
      There was no significant positive associations between the concentrations of
      carbromal administered and mortality in rats or mice of either sex. Adequate
      numbers of animals in all groups survived sufficiently long to be at risk from
      late-developing tumors. Slight dose-related mean body weight depression was
      observed for male rats and for females of both species and the mean body weight
      among dosed male mice was lower than that for controls, indicating that the
      concentrations of carbromal administered to the animals in this bioassay may have
      approximated the maximum tolerated concentrations. None of the statistical tests
      for any site in female rats or in mice of either sex indicated a significant
      positive association between compound administration and tumor incidence. There
      was a significant positive association between the concentrations administered
      and the incidences of adrenal pheochromocytomas in male rats; however, the Fisher
      exact comparisons were not significant. Under the conditions of this bioassay,
      dietary administration of carbromal was not carcinogenic in Fischer 344 rats or
      B6C3F1 mice.

PMID- 12799691
TI  - Bioassay of sodium diethyldithiocarbamate for possible carcinogenicity.
AB  - A bioassay of sodium diethyldithiocarbamate for possible carcinogenicity was
      conducted by administering the test chemical in feed to F344 rats and B6C3F1
      mice. Groups of 50 rats of each sex were administered sodium
      diethyldithiocarbamate at one of two doses, either 1,250 or 2,500 ppm, for 104
      weeks. Groups of 50 mice of each sex were administered sodium
      diethyldithiocarbamate at one of two doses, either 500 or 4,000 ppm, for 108 or
      109 weeks. Matched controls consisted of 16 untreated male rats, 20 untreated
      female rats and 20 untreated mice of each sex. All surviving rats and mice were
      killed at the end of administration of the test chemical. Mean body weights of
      all dosed groups of rats and mice were lower that those of corresponding controls
      and were dose related throughout the bioassay except those of the low-dose male
      rats, which were essentially unaffected by administration of the test chemical.
      Survivals of the rat and mice were unaffected, and no other clinical signs could
      be related to administration of the test chemical; thus, the animals may have
      been able to tolerate higher doses. Sufficient numbers of dosed and control
      animals of each species and sex were at risk for the development of late
      appearing tumors. No tumors occurred in the rats or mice of either sex at
      incidences that were significantly higher in the dosed groups than in the control
      groups. It is concluded that under the conditions of this bioassay, sodium
      diethyldithiocarbamate was not carcinogenic for F344 rats or B6C3F1 mice of
      either sex.

PMID- 12799692
TI  - Bioassay of 2,4-dimethoxyaniline hydrochloride for possible carcinogenicity.
AB  - 2,4-Dimethoxyaniline hydrochloride, the hydrochloride salt of the dye
      intermediate 2,4-dimethoxyaniline, was selected for bioassay by the National
      Cancer Institute because of the increased incidence of bladder cancer among dye
      manufacturing industry workers. Aromatic amines are one of several classes of
      chemicals thought to contribute to the increased cancer risk in this industry. A
      bioassay for the possible carcinogenicity of 2,4-dimethoxyaniline HCl was
      conducted using Fischer 344 rats and B6C3F1 mice. 2,4-Dimethoxyaniline HCl was
      administered in the feed, at either of two concentrations, to groups of 50 male
      and 50 female animals of each species. Twenty animals of each sex and species
      were placed on test as controls. The high and low dietary concentrations of 2,4
      dimethoxyaniline HCl were, respectively, 3,000 and 1,500 ppm for rats and 5,000
      and 2,500 ppm for mice. The compound was administered in the diet for 104 weeks
      to rats and 103 weeks to mice, followed by a 1-week observation period for both
      species. There were no significant positive associations between the
      concentrations of 2,4-dimethoxyaniline HCl administered and mortality in rats or
      mice of either sex. Adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. Dose-related mean
      body weight depression was observed for females of both species, indicating that
      the concentrations of 2,4-dimethoxyaniline HCl administered to these groups may
      have approximated the maximum tolerated concentrations. Compound-related mean
      body weight depression was only slight for male rats and was apparent in male
      mice only until week 50; however follicular-cell hyperplasias and cystic
      follicles of the thyroid were observed in dosed male mice, suggesting that the
      concentrations the male mice received may have approximated the maximum tolerated
      concentrations. Since no distinct mean body weight depression in relation to
      controls, no significant accelerated mortality, and no other signs of toxicity
      were associated with administration of 2,4-dimethoxyaniline HCl to male rats, it
      is possible that these animals may have been able to tolerate a higher dietary
      concentration. There was a significant positive trend between concentration of
      the test chemical and the incidence of a combination of hepatocellular carcinomas
      and adenomas in male mice and an increase in the combination of these lesions in
      female mice. However, no statistically significant differences in tumor incidence
      at any site were observed when dosed rats and mice were compared to their
      respective controls. Under the conditions of this bioassay there was no
      convincing evidence for the carcinogenicity of 2,4-dimethoxyaniline HCl in
      Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male
      Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative
      Synonyms: 2,4-dimethoxybenzenamine hydrochloride; 4-methoxy-o-anisidine
      hydrochloride; 2-methoxy-p-anisidine hydrochloride

PMID- 12799693
TI  - Bioassay of a solution of b-nitrostyrene and styrene for possible
      carcinogenicity.
AB  - A bioassay of a solution of 30 percent b-nitrostyrene and 70 percent styrene for
      possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice.
      The solution of the two test materials in corn oil was administered by gavage, at
      either of two dosages, to groups of 50 male and 50 female animals of each
      species. The high and low dosages utilized in the study were, respectively, 300
      and 150 mg/kg for male rats; 150 and 75 mg/kg for female rats; and 175 and 87.5
      mg/kg for mice of both sexes. These dosages are expressed in terms of the b
      nitrostyrene contained in the styrene solution. Twenty animals of each species
      and sex were placed on test as controls, and were gavaged with corn oil on the
      same schedule as dosed animals. A 79-week period of chemical administration was
      followed by an additional observation period of 29 weeks for rats, and a 78-week
      period of chemical administration was followed by an additional 14-week
      observation period for mice. There was no significant difference between the
      survival of rats dosed with the test solution and that of their controls, and
      there was no significant association between dosage and mortality among female
      mice. There was a significant positive association between dosage and mortality
      among male mice; however, adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-developing tumors. There was distinct
      mean body weight depression when high dose female mice or male rats were compared
      to their controls, indicating that the dosage administered to these animals may
      have approximated the maximum tolerated dosage. Since no distinct mean body
      weight depression, no significantly accelerated mortality, and no other toxic
      effects were associated with the administration of b-nitrostyrene and styrene to
      female rats or male mice, it is possible that these animals may have been able to
      tolerate a higher dosage. There were no significant positive associations between
      administration of the solution and increased tumor incidence in rats of either
      sex. When those male mice having either alveolar/bronchiolar carcinomas or
      alveolar/bronchiolar adenoma were combined and the resulting tumor incidences for
      each group were statistically analyzed, the low dose to control Fisher exact
      comparison was significant. The Cochran-Armitage test and the high dose to
      control comparison, however, were not. No other tests for tumors of any site in
      either male or female mice were significant. Under the conditions of this
      bioassay, there was no convincing evidence for the carcinogenicity of a solution
      of b-nitrostyrene and styrene in Fischer 344 rats or in B6C3F1 mice.

PMID- 12799694
TI  - Bioassay of 2-nitro-p-phenylenediamine for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of 2-nitro-p-phenylenediamine was
      conducted using Fischer 344 rats and B6C3F1 mice. 2-Nitro-p-phenylenediamine was
      administered in the feed, at either of two concentrations, to groups of 50 male
      and 50 female animals of each species. Twenty animals of each sex and species
      were placed on test as controls. The high and low dietary concentrations of 2
      nitro-p-phenylenediamine were, respectively, 1,100 and 550 ppm for male rats,
      2,200 and 1,100 ppm for female rats, and 4,400 and 2,200 ppm for mice of both
      sexes. The compound was administered in the diet for 78 weeks, followed by an
      observation period of 27 weeks for rats and 12 to 13 weeks for mice. There were
      no significant positive associations between the dietary concentrations of 2
      nitro-p-phenylenediamine administered and mortality in rats and mice of either
      sex. Adequate numbers of animals in all groups survived sufficiently long to be
      at risk from late-developing tumors. Mean body weight depression, relative to
      controls, was observed in dosed rats and mice of both sexes, indicating that the
      concentrations administered to these animals may have approximated the maximum
      tolerated dosages. When the female mice in each group, having hepatocellular
      carcinoma or hepatocellular adenoma, were combined and the resulting incidences
      statistically analyzed, there was a significant positive association between
      concentration administered and the incidence of these tumors. This finding was
      supported by a significant high dose to control Fisher exact comparison. No
      tumors occurred in statistically significant increased incidences when dosed male
      or female rats or male mice were compared to their respective controls. Under the
      conditions of this bioassay, dietary administration of 2-nitro-p-phenylenediamine
      was carcinogenic to female B6C3F1 mice, causing an increased incidence of
      hepatocellular neoplasms, primarily hepatocellular adenomas. There was no
      convincing evidence for the carcinogenicity of the compound in Fischer 344 rats
      or in male B6C3F1 mice.

PMID- 12799695
TI  - Bioassay of N-(1-naphthyl)ethylenediamine dihydrochloride for possible
      carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of N-(1-naphthyl)ethylenediamine
      dihydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. N-(1
      Naphthyl)ethylenediamine dihydrochloride was administered in the feed, at either
      of two concentrations, to groups of 50 male and 50 female animals of each
      species. Twenty-five rats of each sex and 50 mice of each sex were placed on test
      as controls. The high and low dietary concentrations of N-(1
      naphthyl)ethylenediamine dihydrochloride administered to rats and male mice were
      0.1 and 0.05 percent, respectively. The high and low time-weighted average
      concentrations administered to female mice were, respectively, 0.3 and 0.2
      percent. The compound was administered in the diet for 104 weeks, followed by an
      observation period of 4 weeks for high dose rats, 3 weeks for low dose rats, low
      dose female mice, and high dose female mice, and 1 week for high dose male mice.
      There were no significant positive associations between the concentrations of N
      (1-naphthyl)ethylenediamine dihydrochloride administered and mortality in rats of
      either sex or in male mice. There was a significant positive association between
      concentration and mortality in female mice. In all groups, except for high dose
      females, adequate numbers of animals survived sufficiently long to be at risk
      from late-developing tumors. Mean body weight depression, in relation to
      controls, was apparent for both sexes of rats and mice, indicating that higher
      concentrations of the test chemical would not have been tolerated by these
      animals. In rats or mice of either sex, there were no statistically significant
      positive associations between the concentration of N-(1-naphthyl)ethylenediamine
      dihydrochloride and tumor incidence. Under the conditions of this bioassay,
      dietary administration of N-(1-naphthyl)ethylenediamine dihydrochloride was not
      carcinogenic in Fischer 344 rats or B6C3F1 mice.

PMID- 12799696
TI  - Bioassay of tetraethylthiuram disulfide for possible carcinogenicity.
AB  - A bioassay of technical-grade tetraethylthiuram disulfide for possible
      carcinogenicity was conducted by administering the test chemical in feed to F344
      rats and B6C3F1 mice. Groups of 50 rats of each sex were administered
      tetraethylthiuram disulfide in the diet at one of two doses, either 300 or 600
      ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test
      chemical at one of two doses, either 500 or 2,000 ppm for the males and either
      100 or 500 ppm for the females, for 108 weeks. Matched controls consisted of 20
      untreated rats and 20 untreated mice of each sex. All surviving animals were
      killed at the ends of the periods of administration of the test chemical. Mean
      body weights of the dosed rats and mice of each sex were lower than those of
      corresponding controls and were dose related throughout most of the bioassay.
      Mortality was not significantly affected by administration of the test chemical
      to either the rats of the mice, except for the female rats, in which the
      mortality was higher in the control group than in the dosed groups; however, the
      survival at the end of the bioassay was 65% or greater in all dosed and control
      groups of rats and mice of either sex, and sufficient numbers of animals were at
      risk in each group for the development of late-appearing tumors. No tumors
      occurred in the rats or mice of either sex at incidences that were significantly
      higher in dosed groups than in corresponding control groups. It is concluded that
      under the conditions of this bioassay, tetraethylthiuram disulfide was not
      carcinogenic for F344 rats or B6C3F1 mice of either sex.

PMID- 12799697
TI  - Bioassay of 4-chloro-o-toluidine hydrochloride for possible carcinogenicity.
AB  - A bioassay of 4-chloro-o-toluidine hydrochloride for possible carcinogenicity was
      conducted by administering the test chemical in feed to F344 rats and B6C3F1
      mice. Groups of 50 rats of each sex were administered 4-chloro-o-toluidine in the
      diet at one of two doses, either 1,250 or 5,000 ppm, for 107 weeks. Groups of 50
      mice of each sex were administered the test chemical in the diet at one of two
      doses, either 3,750 or 15,000 ppm for the males and either 1,250 or 5,000 ppm for
      females, for 99 weeks, except for the high dose females (92 weeks). Matched
      controls consisted of 20 untreated rats and 20 untreated mice of each sex. All
      surviving animals were killed at the end of administration of the test chemical.
      Mean body weights of the high-dose rats and the low- and high-dose mice of each
      sex were lower than those of corresponding controls, and those of the mice were
      dose related. Mortality was not significantly affected by administration of the
      test chemical to rats of either sex and survival was 75% or greater at the end of
      the study in dosed and control groups. Sufficient numbers of rats were at risk
      for the development of late-appearing tumors. In mice, mortality was dose related
      for each sex. In rats no tumors occurred at incidences which could clearly be
      related to administration of the test chemical. In both male and female mice,
      hemangiosarcomas occurred at incidences that were dose related (P</= 0.001), and
      in direct comparisons the incidences in the high-dose males and the low-and high
      dose females were significantly higher (P<0.001) than those in the corresponding
      controls (males: controls 0/20; low-dose 3/50; high-dose 37/50; females: controls
      0/18; low-dose 40/49, high-dose 39/50). The combined incidences of
      hemangiosarcomas and hemangiomas also were dose related and were significantly
      higher in the dosed groups of male and female mice than in the corresponding
      controls. There was a high incidence of hemosiderin deposit in the renal tubular
      epithelium, particularly in mice with hemangiosarcomas. It is concluded that
      under the conditions of this bioassay, 4-chloro-o-toluidine hydrochloride was not
      carcinogenic for F344 rats but was carcinogenic for B6C3F1 mice, including
      hemangiosarcomas and hemangiomas in both males and females. Levels of Evidence of
      Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive
      Female Mice: Positive Synonym: 2-amino-4-chlorotoluene hydrochloride

PMID- 12799698
TI  - Bioassay of N-nitrosodiphenylamine for possible carcinogenicity.
AB  - A bioassay of N-nitrosodiphenylamine for possible carcinogenicity was conducted
      by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups
      of 50 rats of each sex were administered N-nitrosodiphenylamine at one of two
      doses, either 1,000 or 4,000 ppm, for 100 weeks. Matched controls consisted of 20
      untreated rats of each sex. All surviving rats were killed at the end of
      administration of the test chemical. Groups of 50 male mice were administered N
      nitrosodiphenylamine at one of two doses, either 10,000 or 20,000 ppm, for 101
      weeks. Groups of 50 female mice were administered the test chemical at one of two
      doses, initially 5,000 or 10,000 ppm, for 38 weeks. Because of excessive
      depression in the amount of mean body weight gained in the dosed groups, the
      doses for the females were then reduced to 1,000 and 4,000 ppm, respectively, and
      administration at the lowered doses was continued for 60 weeks. The time-weighted
      average doses for the female mice were either 2,315 or 5,741 ppm. Matched
      controls consisted of 20 untreated mice of each sex. All surviving mice were
      killed at the end of administration of the test chemical. Mean body weights of
      dosed rats and mice of each sex were lower than those of corresponding controls,
      and were dose related throughout the bioassay, except for those of female rats
      during the first part of the bioassay. Mortality was dose related in the female
      rats, but was not affected when the test chemical was administered to the male
      rats or the male or female mice. Survival at the end of the bioassay was 64% or
      greater in the dosed and control groups of rats and mice of each sex, and
      sufficient numbers of animals were at risk in all groups for the development of
      late-appearing tumors. Transitional-cell carcinomas of the urinary bladder
      occurred at incidences that were dose related (P</= 0.001) in both male and
      female rats, and in direct comparisons the incidences of these tumors in the high
      dose groups of each sex were significantly higher (P</= 0.001) than those in the
      corresponding controls (males: controls 0/19; low-dose 0/46; high-dose 16/45;
      females: controls 0/18; low-dose 0/48; high-dose 40/49). The possible mechanism
      by which these tumors were induced, such as calculi formation in the bladder or
      nitrosation of amines present in feed to a carcinogenic nitrosoamine, is unknown.
      Fibromas of the integumentary system occurred in male rats at incidences that
      were dose related (P=0.003), although in direct comparisons the incidences of
      these tumors in the individual dosed groups were not significantly higher than
      those in the control group (controls 1/20, or 5%; low-dose 1/50, or 2%; high-dose
      10/50, or 20%). The incidence of fibromas of the integumentary system in
      historical-control male F344 rats at this laboratory is 6/285, or 2%. These
      results suggest an association of the fibromas in the male rats with the
      administration of the test chemical. No tumors occurred in the mice of either sex
      at incidences that were significantly higher in the dosed groups than in the
      corresponding control groups. The only changes related to compound administration
      were chronic inflammatory lesions in the urinary bladders of dosed mice. It is
      concluded that under the conditions of this bioassay, N-nitrosodiphenylamine was
      carcinogenic for both sexes of F344 rats, including transitional-cell carcinomas
      of the urinary bladder, but was not carcinogenic for B6C3F1 mice of either sex.

PMID- 12799699
TI  - Bioassay of calcium cyanamide for possible carcinogenicity.
AB  - A bioassay of formulated calcium cyanamide for possible carcinogenicity was
      conducted by administering the test chemical in feed to F344 rats and B6C3F1
      mice. Groups of 50 rats of each sex were administered a commercial formulation
      containing 63% calcium cyanamide in the diet at one of two doses, either 100 or
      200 ppm for the males and either 100 or 400 ppm for the females, for 107 weeks.
      Groups of 50 mice of each sex were administered the test chemical at one of two
      doses, either 500 or 2,000 ppm, for 100 weeks. Matched controls consisted of 20
      untreated rats and 20 untreated mice of each sex. All surviving animals were
      killed at the end of administration of the test chemical. Mean body weights of
      the dosed rats and mice were only slightly lower than those of corresponding
      controls, except for the low-dose female mice, whose mean body weights were
      unaffected by the test chemical. Mortality was dose related only in male mice.
      Survival was 70% or greater in all dosed and control groups of each species and
      sex at the end of the bioassay, and sufficient numbers of animals were at risk in
      all groups for the development of late-appearing tumors. Both rats and mice may
      have been able to tolerate higher doses. No tumors occurred in the dosed rats of
      either sex at incidences that could clearly be related to administration of the
      calcium cyanamide. However, in the subchronic studies performed with the rats,
      calcium cyanamide was found to cause diffuse follicular hyperplasia of the
      thyroid, with periglandular fibrosis and prominent periglandular vascularity. In
      male mice, hemangiosarcomas were dose related in the males (P=0.006); however, in
      direct comparisons, incidences in the individual dosed groups were not
      significantly higher than those in the control group (controls 1/20 (5%); low
      dose 2/50 (4%); high-dose 10/50 (20%)). The incidence of these tumors in
      historical-control male B6C3F1 mice was (13/323 (4%)), and the highest incidence
      observed was 2/19 (10%). In female mice, lymphomas or leukemias were dose related
      (P=0.009), and in a direct comparison the incidence of these tumors in the high
      dose group was significantly higher (P=0.006) than that in the control group
      (controls 1/20 (5%); low-dose 11/46 (24%); high-dose 18/50 (36%)); however, the
      incidence of the lymphomas or leukemias in historical-control female B6C3F1 mice
      was 67/324 (21%), suggesting that the incidence of these tumors in the matched
      control group of the present bioassay may have been abnormally low. Thus, neither
      the incidences of hemangiosarcomas of the circulatory system in male mice nor of
      lymphomas or leukemias in the female mice can clearly be related to
      administration of the test chemical. It is concluded that under the conditions of
      this bioassay, the test formulation of calcium cyanamide was not carcinogenic for
      F344 rats or B6C3F1 mice of either sex.

PMID- 12799700
TI  - Bioassay of 2,4-diaminotoluene for possible carcinogenicity.
AB  - A bioassay of 2,4-diaminotoluene for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered 2,4-diaminotoluene at one of two doses,
      initially either 125 or 250 ppm, for 40 weeks. Because of excessive depression in
      the amount of mean body weight gained in both low- and high-dose groups, doses
      were then reduced to 50 and 100 ppm, respectively. Administration of 50 ppm to
      the low-dose groups was continued for 63 weeks, and surviving animals in these
      groups were then killed. Surviving animals in the high-dose males and females
      administered 100 ppm were killed at the end of 39 and 44 weeks, respectively, due
      to morbidity. The time-weighted average dose was 79 ppm for the low-dose male and
      females for 103 weeks, 176 ppm for the high-dose males for 79 weeks, and 171 ppm
      for the high-dose females for 84 weeks. Matched controls consisted of 20
      untreated rats of each sex. Groups of 50 mice of each sex were administered 2,4
      diaminotoluene at one of two doses, either 100 or 200 ppm, for 101 weeks. Matched
      controls consisted of 20 untreated mice of each sex. Surviving mice were killed
      at the end of administration of the test chemical. Mean body weights of dosed
      male and female rats and mice were lower than those of corresponding controls and
      were dose related except for the low-dose male mice, for which mean body weights
      were only slightly lower than those of controls. Mortality was not dose related
      in either the male or female mice, but was dose related in both the male and
      female rats. Survival was decreased and lesions of hepatonephrotoxicity were
      observed in the animals administered the 2,4-diaminotoluene. In the rats,
      hepatocellular carcinomas or neoplastic nodules occurred at incidences that were
      dose related in both the males (P=0.014) and the females (P=0.008). In direct
      comparisons of incidences of the tumors in control and dosed groups, the
      incidence in the high-dose male group had a P value of 0.026 (males: controls
      0/20, low-dose 5/49, high-dose 10/50; females: controls 0/20; low-dose 0/50, high
      dose 6/49). The significance of the occurrence of these tumors in both the male
      and female rats was supported by the high incidences of associated nonneoplastic
      lesions of the liver in the dosed groups and by low incidences of liver tumors in
      historical-control male or female F344 rats at the same laboratory. In addition,
      carcinomas or adenomas of the mammary gland occurred in the female rats at
      incidences that were dose related (P=0.002) and in direct comparisons were higher
      in the dosed groups (P<0.001) than in the control group (control 1/20; low-dose
      38/50, high-dose 41/50). In male rats, fibromas of the subcutaneous tissue
      occurred at incidences that were dose related (P=0.004) and in direct comparisons
      were higher in the dosed groups (P</= 0.020) than in the control group (controls
      0/20, low-dose 15/30, high-dose 19/50). In the mice, hepatocellular carcinomas
      occurred in the females at incidences that were dose related (P=0.002) and in
      direct comparisons were higher in dosed groups (P</= 0.007) than in the control
      group (controls 0/19, low-dose 13/47, high-dose 18/46). In addition, lymphomas
      occurred at a significant incidence (P<0.001) in the low-dose female mice
      (controls 2/19, low-dose 29/47, high-dose 11/46). No tumors occurred at
      significantly increased incidences in the dosed male mice. Under the conditions
      of this bioassay, 2,4-diaminotoluene was carcinogenic for F344 rats, inducing
      hepatocellular carcinomas or neoplastic nodules in both males and females and
      carcinomas or adenomas of the mammary gland in females. The test chemical was
      also carcinogenic for female B6C3F1 mice, inducing hepatocellular carcinomas. The
      incidence of lymphomas in the female mice suggested that these tumors may also
      have been related to administration of the test chemical.

PMID- 12799701
TI  - Bioassay of phthalamide for possible carcinogenicity.
AB  - A bioassay of phthalamide for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered phthalamide at one of two doses, either
      15,000 or 30,000 ppm for the males and either 5,000 or 10,000 ppm for the
      females, for 106 weeks. Groups of 50 mice of each sex were administered the test
      chemical at one of two doses, 25,000 or 50,000 ppm for the males, and at one of
      three doses, 6,200, 12,500, or 25,000 ppm, for the females, for 103 or 105 weeks.
      Matched controls consisted of 20 untreated rats of each sex, 20 untreated male
      mice, and two groups of 20 untreated female mice. All surviving rats and mice
      were killed at the end of administration of the test chemical. Mean body weights
      of the dosed groups of rats and mice were either slightly lower than those of
      corresponding control groups or essentially unaffected by administration of the
      test chemical. Also, survival was unaffected in the rats and mice except for
      early deaths in the high- and mid-dose groups of female mice. Survival was 66% or
      greater at the end of the bioassay in all dosed groups and control groups of each
      species and sex except for the high-dose group of female mice (36%). With the
      exception of the high-dose female mice, sufficient numbers of animals were at
      risk in all groups for the development of late-appearing tumors. No tumors
      occurred in the rats or mice of either sex at incidences that were significantly
      higher in the dosed groups than in the corresponding control groups. However,
      phthalamide produced toxic lesions in the livers of male and female rats and the
      urinary systems of female rats and mice. The presence of nonneoplastic lesions
      suggests that the MTD may have been used or exceeded. It is concluded that under
      the conditions of this bioassay, phthalamide was not carcinogenic for F344 rats
      or B6C3F1 mice of either sex.

PMID- 12799702
TI  - Bioassay of 2,4,5-trimethylaniline for possible carcinogenicity.
AB  - A bioassay of 2,4,5-trimethylaniline for possible carcinogenicity was conducted
      by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups
      of 50 rats and 50 mice of each sex were administered 2,4,5-trimethylaniline at
      one of two doses, either 200 or 800 ppm for the rats and either 50 or 100 ppm for
      the mice, for 101 weeks. Matched controls consisted of 20 untreated rats and 20
      untreated mice of each sex. All surviving animals were killed at the end of
      administration of the test chemical. Mean body weights of the dosed male and
      female rats were generally lower than those of corresponding controls; mean body
      weights of the dosed mice were only slightly lower in the males than in the
      corresponding controls and were unaffected or affected irregularly in the
      females. Survival was not affected significantly when the rats or mice were
      administered the test chemical and was 70% or greater in all dosed or control
      groups. Sufficient numbers of animals were at risk for late-appearing tumors. In
      the rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences
      that were dose related in both males and females (P</= 0.001), and in direct
      comparisons the incidences were slightly higher in the high-dose males, high-dose
      females, and low-dose females (P</= 0.004) than in corresponding controls (males:
      controls 1/19; low-dose 6/50; high-dose 20/50; females: controls 0/20; low-dose
      12/49, high-dose 27/50). In addition, alveolar/bronchiolar carcinomas or adenomas
      occurred in the female rats at incidences that were dose related (P=0.003), and
      in a direct comparison the incidence was significantly higher in the high-dose
      group (P=0.017) than in the corresponding control group (controls 0/20; low-dose
      3/43; high-dose 11/50). In the female mice, hepatocellular carcinomas occurred at
      incidences that were dose related (P</= 0.001), and in direct comparisons the
      incidences were significantly higher (P</= 0.001) in the low- and high-dose
      animals than in the corresponding controls (controls 0/20, low-dose 18/49, high
      dose 40/50). Because historical records of this laboratory for control B6C3F1
      male mice show a relatively high incidence of hepatocellular carcinomas, an
      increased incidence of these tumors in 2,4,5-trimethylaniline dosed male mice as
      compared with matched controls could not be clearly associated with
      administration of the test compound. It is concluded that under the conditions of
      this bioassay, 2,4,5-trimethylaniline was carcinogenic for male and female F344
      rats and female B6C3F1 mice, inducing hepatocellular carcinomas or neoplastic
      nodules in the rats of each sex, alveolar/bronchiolar carcinomas in the female
      rats, and hepatocellular carcinomas in female mice.

PMID- 12799703
TI  - Bioassay of phthalic anhydride for possible carcinogenicity.
AB  - A bioassay of phthalic anhydride for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered the test chemical at one of two doses,
      initially either 25,000 or 50,000 ppm, for 32 weeks. Because of excessive
      depressions in the amount of body weight gained in the dosed groups, the doses
      for the males were then reduced to 12,500 and 25,000 ppm, respectively, and the
      doses for the females were reduced to 6,250 and 12,500 ppm. Administration of the
      test chemical at the lowered doses was continued for 72 weeks. The time-weighted
      average doses for the males were either 16,346 or 32,692 ppm, and those for the
      females were either 12,019 or 24,038 ppm. Matched controls consisted of 20
      untreated mice of each sex. All surviving mice were killed at the end of the
      period of administration of the test chemical. Mean body weights of the high-dose
      male rats and of the low- and high-dose mice of each sex were lower than those of
      the corresponding controls; mean body weights of the low-dose male rats and of
      both the low- and high-dose female rats were essentially unaffected by
      administration of the test chemical. Depressions in the amount of body weight
      gained in the male and female mice were dose related throughout the bioassay.
      Survivals of the rats and mice were not affected by administration of the test
      chemical. No tumors occurred in the rats or mice of either sex at incidences that
      could be clearly related to the administration of the test chemical. It is
      concluded that under the conditions of this bioassay, phthalic anhydride was not
      carcinogenic for F344 rats or B6C3F1 mice of either sex.

PMID- 12799704
TI  - Bioassay of (2-chloroethyl)trimethylammonium chloride (CCC) for possible
      carcinogenicity.
AB  - A bioassay of (2-chloroethyl)trimethylammonium chloride for possible
      carcinogenicity was conducted by administering the test chemical in feed to F344
      rats and B6C3F1 mice. Groups of 50 rats of each sex were administered either
      1,500 or 3,000 ppm of the compound for 108 weeks, and 50 mice of each sex were
      administered 500 or 2,000 ppm for 102 weeks. Matched controls consisted of 20
      untreated and 20 untreated mice of each sex. All surviving animals were killed at
      the end of the period of administration of the test chemical. Mean body weights
      of dosed rats and mice were lower than those of corresponding controls for part
      or all of the bioassay, except for the dosed male mice, whose mean body weights
      were essentially the same as those of the corresponding controls. Survival was
      not affected significantly in any of the dosed groups of rats or mice and was at
      least 64% in every dosed or control group of each species at the end of the
      bioassay. Sufficient numbers of dosed and control rats and mice of each sex were
      at risk for the development of late-appearing tumors. Since there was virtually
      no decrease in mean body weight in dosed male mice and only a slight decrease in
      female mice, and since there were no other toxic signs and no dose-related
      mortality, the animals may have been able to tolerate higher doses. No tumors
      occurred in the rats or mice of either sex at incidences that could be associated
      with administration of the test chemical. It is concluded that under the
      conditions of this bioassay, (2-chloroethyl)trimethylammonium chloride was not
      carcinogenic for F344 rats or B6C3F1 mice of either sex.

PMID- 12799705
TI  - Bioassay of methyl parathion for possible carcinogenicity.
AB  - A bioassay of methyl parathion for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered methyl parathion at one of two doses,
      initially either 62.5 or 125 ppm. These doses were maintained for 102 weeks for
      the females; however, due to decreased mean body weight gain in the dosed males,
      the low and high doses for the males were reduced after 37 weeks to 20 and 50
      ppm, respectively, and administration at the lowered doses was continued for 65
      weeks. The time-weighted average doses for the male mice were 35 and 77 ppm,
      respectively, for the low- and high-dose groups. Matched controls consisted of 20
      untreated mice of each sex. All surviving mice were killed at the end of
      administration of the test chemical. Mean body weights of the dosed male and
      female rats and mice were lower than those of the corresponding controls
      throughout the bioassay and were dose related. Survival was unaffected in both
      species except for an increase in mortality in the high-dose female rats, in
      which 46% of the animals were alive at the end of the study. No tumors occurred
      in any of the groups of rats or mice of either sex at incidences that were
      significantly higher in the dosed groups than in the corresponding control
      groups. It is concluded that under the conditions of this bioassay, methyl
      parathion was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

PMID- 12799706
TI  - Bioassay of p,p'-ethyl-DDD for possible carcinogenicity.
AB  - A bioassay of p,p'-ethyl-DDD for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered p,p'-ethyl-DDD at one of two doses, either
      3,500 or 7,000 ppm, for 105 weeks. Matched controls consisted of 20 untreated
      rats of each sex. All surviving rats were killed at the end of administration of
      the test chemical. Groups of 50 male mice were administered p,p'-ethyl-DDD at one
      of two doses, either 2,500 or 5,000 ppm, for 105 weeks. Groups of 50 female mice
      were administered the test chemical at one of two doses, initially either 5,000
      or 10,000 ppm. Because of excessive lowered body weights in the dosed groups of
      females, the doses for the females were reduced after 48 weeks to 1,000 and 3,000
      ppm, respectively, and administration at the lowered doses was continued for 57
      weeks. The time-weighted average doses for the female mice were 2,828 and 6,200
      ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving
      mice were killed at the end of administration of the test chemical. No tumors
      occurred in the male or female rats or in the male mice at incidences that could
      clearly be related to administration of the test chemical. In female mice,
      hepatocellular carcinomas or adenomas occurred at incidences that were dose
      related (P=0.011), but in direct comparisons the incidences in the individual
      dosed groups were not significantly higher than that in the corresponding control
      group. Although the occurrence of hepatocellular carcinomas or adenomas in the
      dosed female mice are not clearly related to the administration of the test
      chemical, the increased incidence of these tumors in the high-dose group suggests
      that the tumors may be related to the administration of p,p'-ethyl-DDD. It is
      concluded that under the conditions of this bioassay, p,p'-ethyl-DDD was not
      carcinogenic for male or female F344 rats or male B6C3F1 mice. However, the
      occurrence of hepatocellular carcinomas and adenomas in female mice was
      suggestive of a carcinogenic effect.

PMID- 12799707
TI  - Bioassay of 2,4,6-trichlorophenol for possible carcinogenicity.
AB  - A bioassay of 2,4,6-trichlorophenol for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered 2,4,6-trichlorophenol at one of two doses,
      either 5,000 or 10,000 ppm, for 106 or 107 weeks. Matched controls consisted of
      20 untreated rats of each sex. All surviving rats were killed at the end of
      administration of the test chemical. Groups of 50 male mice were administered
      2,4,6-trichlorophenol at one of two doses, either 5,000 or 10,000 for 105 weeks.
      Groups of 50 female mice were administered the test chemical at one of two doses,
      initially either 10,000 or 20,000 ppm, for 38 weeks. Because of excessively
      lowered body weights in the dosed groups of the females, the doses for the
      females were then reduced to 2,500 and 5,000 ppm, respectively, and
      administration at the lower doses was continued for 67 weeks. The time-weighted
      average doses for the female mice were either 5,214 or 10,428 ppm. Matched
      controls consisted of 20 untreated mice of each sex. All surviving mice were
      killed at the end of administration of the test chemical. Mean body weights of
      dosed rats and mice of each sex were lower than those of corresponding controls
      and were dose related throughout the bioassay. Survivals to the end of the
      experiment were 68% or greater in all groups of rats and 80% or greater in all
      groups of mice. In the male rats, lymphomas or leukemias occurred at incidences
      that were dose related (P=0.006) and in direct comparisons were significantly
      higher in the low-dose(P=0.019) and high-dose (P=0.004) groups than in the
      corresponding control group (controls 4/20; low-dose 25/50; high-dose 29/50).
      Leukocytosis and monocytosis of the peripheral blood and hyperplasia of the bone
      marrow also occurred in some dosed male rats not having lymphoma or leukemia. In
      female rats, monocytic leukemia did not occur at incidences that were
      significant. However, as in the male rats, leukocytosis and monocytosis of the
      peripheral blood and hyperplasia of the bone marrow occurred in the dosed female
      rats but not in the controls (blood leukocytosis and monocytosis: controls 0/20,
      low-dose 6/50, high-dose 3/50; bone marrow hyperplasia: controls 0/20, low-dose
      16/50, high-dose 2/50). In both the male and female mice, hepatocellular
      carcinomas or adenomas occurred at incidences that were dose related (P<0.001),
      and in direct comparisons were significantly higher in the low- and high-dose
      male groups and the high-dose female group (P</= 0.001) than in the corresponding
      control groups (males: controls 4/20, low-dose 32/49, high-dose 39/47; females:
      controls 1/20, low-dose 12/50, high-dose 24/48). It is concluded that under the
      conditions of this bioassay, 2,4,6-trichlorophenol was carcinogenic in male F344
      rats, inducing lymphomas or leukemias. The test chemical was also carcinogenic in
      both sexes of B6C3F1 mice, inducing hepatocellular carcinomas or adenomas.

PMID- 12799708
TI  - Bioassay of azobenzene for possible carcinogenicity.
AB  - A bioassay of azobenzene for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex were administered azobenzene at one of two doses, either 200
      or 400 ppm, for 105 or 106 weeks. Matched controls consisted of 20 untreated rats
      of each sex. All surviving rats were killed at the end of administration of the
      test chemical. Groups of 50 male mice were administered azobenzene at one of two
      doses, either 200 or 400 ppm, for 105 weeks. Groups of 50 female mice were
      administered the test chemical at one of two doses, initially 400 or 800 ppm, for
      38 weeks. Because of excessively lowered body weights in the dosed groups of the
      females, doses for the females were then reduced to 100 and 400 ppm,
      respectively, and administration at the lowered doses was continued for 67 or 68
      weeks. The time-weighted average doses for the female mice were either 208 or 545
      ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving
      mice were killed at the end of administration of the test chemical. Mean body
      weights of dosed rats and mice of each sex were lower than those of corresponding
      controls, and were generally dose related throughout the bioassay. Mortality was
      dose related in the male rats and the female mice, but was not significantly
      affected in either the female rats or the male mice. Survival was 70% or greater
      at week 90 on study in all dosed and control groups of each species and sex;
      thus, sufficient numbers of animals were at risk in all groups for the
      development of late-appearing tumors. In rats, a large number of sarcomas,
      including fibrosarcomas, hemangiosarcomas, and osteosarcomas in both males and
      females and malignant hemangiopericytomas in females, occurred in the spleen and
      other abdominal organs at incidences that were dose related in each sex (P<0.001)
      and that in direct comparisons were significantly higher (P<0.001) in the high
      dose groups of each sex than in the corresponding control groups (males:
      controls, 0/20, low-dose 6/49, high-dose 31/49; females: controls 0/20, low-dose
      5/50, high-dose 21/50). In mice, no tumors occurred in either males or females at
      incidences that were significantly higher in the dosed groups than in the
      corresponding control groups. It is concluded that under the conditions of this
      bioassay, azobenzene was carcinogenic (sarcomagenic) for F344 rats, inducing
      various types of sarcomas in the spleen and other abdominal organs of both males
      and females. The test chemical was not carcinogenic for B6C3F1 mice of either
      sex.

PMID- 12799709
TI  - Bioassay of o-toluidine hydrochloride for possible carcinogenicity.
AB  - A bioassay of o-toluidine hydrochloride for possible carcinogenicity was
      conducted by administering the test chemical in feed to F344 rats and B6C3F1
      mice. Groups of 50 rats of each sex and 50 mice of each sex were administered o
      toluidine hydrochloride at one of several doses, either 3,000 or 6,000 ppm for
      rats and either 1,000 or 3,000 ppm for the mice, for 101 to 104 weeks. Matched
      controls consisted of 20 untreated rats of each sex and 20 untreated mice of each
      sex. All surviving rats and mice were killed at the end of administration of the
      test chemical. Mean body weights of dosed male and female rats and mice were
      lower than those of corresponding matched controls and were dose related.
      Mortalities of the male and female rats were dose related and were relatively
      high at the end of the bioassay. Mortalities of the male and female mice were
      not, however, significantly affected by administration of the test chemical. In
      rats, the administration of the test chemical induced several types of sarcomas
      of the spleen and other organs in both males and females, mesotheliomas of the
      abdominal cavity or scrotum in males, and transitional-cell carcinomas of the
      urinary bladder in females. Administration of the o-toluidine hydrochloride also
      resulted in increased incidences of fibromas of the subcutaneous tissue in the
      males and fibroadenomas or adenomas of the mammary gland in females. In mice,
      hemangiosarcomas were induced at various sites in males, and hepatocellular
      carcinomas or adenomas were induced in females. Under the conditions of this
      bioassay, o-toluidine hydrochloride was carcinogenic in both male and female F344
      rats and B6C3F1 mice, producing a significant increased incidence of one or more
      types of neoplasms.

PMID- 12799710
TI  - Bioassay of ethyl tellurac for possible carcinogenicity.
AB  - A bioassay of technical-grade ethyl tellurac for possible carcinogenicity was
      conducted by administering the preparation in feed to F344 rats and B6C3F1 mice.
      Groups of 50 rats of each sex were administered ethyl tellurac at one of two
      doses, either 300 or 600 ppm for the males and either 150 or 300 ppm for the
      females, for 105 weeks. Matched controls consisted of 20 untreated rats of each
      sex. All surviving rats were killed at 105 weeks. Groups of 50 mice of each sex
      were administered ethyl tellurac at one of two doses, initially either 2,500 or
      5,000 ppm. Due to signs of toxicity in the dosed animals, these doses were
      reduced to 500 and 2,000 ppm, respectively, starting at week 41 for the males and
      at week 38 for the females. The reduced doses were maintained for 66 weeks for
      the males; for the females, the reduced doses were raised after 3 weeks to 2,000
      and 5,000 ppm, respectively, and maintained at these levels for 66 weeks. The
      time-weighted average doses for the males were either 1,255 or 3,132 ppm; for the
      females, either 2,132 or 4,915 ppm. Matched controls consisted of 20 untreated
      mice of each sex. All surviving mice were killed at 106 weeks. Mean body weights
      of the dosed groups of rats or mice were lower than those of corresponding
      controls throughout most or all of the bioassay. No other clinical signs in the
      rats or mice were clearly related to administration of the test chemical.
      Survival of the rats and the mice was not affected by the chemical, and
      sufficient numbers of all groups were at risk for the development of late
      appearing tumors. In the male rats, mesotheliomas occurred at incidences that
      were dose related (P=0.012); in direct comparisons, the incidences of the tumors
      in the individual dosed groups were not significantly higher than that in the
      control group (controls 0/20, low-dose 2/49, high-dose 8/50). However, the
      historical-control data at this laboratory indicate an incidence of 12/416 (2.9%)
      in male F344 rats compared with 8/50 (16%) in the male high-dose group in this
      study. In the female rats, no tumors occurred at incidences that were related to
      administration of the test chemical. In both male and female mice, adenomas of
      the lacrimal (harderian) gland of the eye occurred in the dosed groups, but not
      in the corresponding controls (males: controls 0/17; low-dose 16/46, high-dose
      10/49; females: controls 0/20, low-dose 6/50, high-dose 5/49). The incidences in
      the dosed groups were not high enough to show statistically significant dose
      related trends. However, in direct comparisons of dosed and control groups of
      male mice, the incidence was statistically significant in the low-dose males
      (P=0.003). In female mice, direct comparisons of dosed and control groups
      indicated that the incidence of this tumor was not statistically significant. It
      is concluded that under the conditions of this bioassay, ethyl tellurac was not
      carcinogenic for F344 rats or B6C3F1 mice of either sex. The incidence of
      mesotheliomas in dosed male rats and the incidence of adenomas of the lacrimal
      (harderian) gland of the eye in dosed mice of either sex provided evidence which
      was suggestive but under the conditions of the bioassay insufficient to establish
      the carcinogenicity of ethyl tellurac in these animals.

PMID- 12799711
TI  - Bioassay of lead dimethyldithiocarbamate for possible carcinogenicity.
AB  - A bioassay of technical-grade lead dimethyldithiocarbamate for possible
      carcinogenicity was conducted by administering the test chemical in feed to F344
      (Fischer) rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each
      sex were administered lead dimethyldithiocarbamate at one of two doses, either 25
      or 50 ppm, for 104 or 105 weeks. Matched controls consisted of 20 untreated rats
      and 20 untreated mice of each sex. All surviving animals were killed at the end
      of the period of administration of the test chemical. Mean body weights of the
      dosed male rats and female mice were slightly lower than those of the
      corresponding controls; mean body weights of the dosed female rats and male mice
      were essentially the same as those of the corresponding controls. Survival rats
      in both species were unaffected by administration of the test chemical. The lack
      of toxicity in both species suggests that a maximum tolerated dose level may not
      have been used. Therefore, the studies may not have been conducted using maximum
      sensitivity for the assessment of the possible carcinogenicity of lead
      dimethyldithiocarbamate. No tumors occurred in the rats or mice of either sex at
      incidences that were significantly higher in the dosed groups than in the control
      groups. It is concluded that under the conditions of this bioassay, lead
      dimethyldithiocarbamate was not carcinogenic for F344 rats or B6C3F1 mice of
      either sex.

PMID- 12799712
TI  - Bioassay of butylated hydroxytoluene (BHT) for possible carcinogenicity.
AB  - A bioassay of BHT for possible carcinogenicity was conducted by administering the
      test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice
      of each sex were administered BHT at one of two doses, either 3,000 or 6,000 ppm;
      the rats for 105 weeks and the mice for 107 or 108 weeks. Matched controls
      consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving
      animals were killed at the end of administration of the test chemical. Mean body
      weights of the dosed rats and mice were lower than those of the corresponding
      controls and were dose related throughout most of the bioassay. Survival was not
      affected significantly in the dosed groups of rats or mice, and the survival was
      60% or greater in all dosed or control groups of rats and mice of each sex at the
      end of the bioassay. Sufficient number of animals were at risk for the
      development of late-appearing tumors. Alveolar/bronchiolar carcinomas or adenomas
      occurred in the female mice at a significant incidence in the low-dose group
      (P=0.009) but not in the high dose group, and the incidences were not
      significantly dose related (control 1/20, low-dose 16/46, high-dose 7/50). Thus,
      these lung tumors in the female cannot clearly be related to the administration
      of the BHT. No tumors occurred in either male or female rats at incidences that
      were significantly higher in dosed groups than in corresponding control groups.
      Nonneoplastic lesions that may have been related to the administration of the
      test chemical included focal alveolar histiocytosis at increased incidences in
      the dosed female rats and various lesions of the liver at increased incidences in
      the dosed male mice. It is concluded that under the conditions of this bioassay,
      BHT was not carcinogenic for F344 rats or B6C3F1 mice.

PMID- 12799713
TI  - Bioassay of N,N'-diethylthiourea for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of N,N'-diethylthiourea was conducted
      using Fischer 344 rats and B6C3F1 mice. N,N'-Diethylthiourea was administered in
      the feed, at either of two concentrations, to groups of 50 males and 50 females
      of each species. Twenty animals of each sex and species, except for 19 male mice,
      were placed on test as controls. The high and low dietary concentrations of N,N'
      diethylthiourea were, respectively, 250 and 125 ppm for rats and 500 and 250 ppm
      for mice. The compound was administered in the diet for 103 weeks, followed by an
      observation period of 1 week for all dosed groups. There were no significant
      positive associations between the dosages of N,N'-diethylthiourea administered
      and mortality in rats or mice of either sex. Adequate numbers of animals in all
      dose groups survived sufficiently long to be at risk from late-developing tumors.
      Compound-related mean body weight depression was apparent among dosed male and
      female mice when compared to their respective controls,indicating that the
      concentrations of N,N'-diethylthiourea administered to mice may have approximated
      the maximum tolerated dosages. There were statistically significant elevated
      incidences of follicular-cell carcinomas of the thyroid in high dose male rats.
      In addition, there were statistically significant elevated incidences of a
      combination of thyroid follicular-cell carcinomas and follicular-cell adenomas in
      high dose male and female rats. Under the conditions of this bioassay, N,N'
      diethylthiourea was carcinogenic to Fischer 344 rats, causing follicular-cell
      carcinomas of the thyroid in males and follicular-cell neoplasms of the thyroid
      in females. There was no evidence for the carcinogenicity of the compound in
      B6C3F1 mice.

PMID- 12799714
TI  - Bioassay of 1-phenyl-2-thiourea for possible carcinogenicity.
AB  - A bioassay of 1-phenyl-2-thiourea for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 1-Phenyl-2-thiourea was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The high and low concentrations of 1-phenyl-2-thiourea
      utilized in the chronic bioassay were, respectively, 120 and 60 ppm for rats and
      300 and 150 ppm for mice. Twenty animals of each species and sex were placed on
      test as controls. A 78-week period of chemical administration was followed by an
      additional observation period of 26 weeks for rats and 13 weeks for mice.
      Adequate numbers of animals in all groups survived sufficiently long to be at
      risk from late-developing tumors. Distinct dose-related depression of mean body
      weight gain was observed in male and female mice when compared with their
      controls, but growth retardation was not observed in any dosed rat group. In
      addition, since no significant accelerated mortality or other toxic effects were
      associated with the dietary administration of 1- phenyl-2-thiourea to rats, it is
      possible that the compound was not administered to these animals at the maximum
      tolerated concentrations. There were no tumors in either sex of rats or mice for
      which a significant positive association could be established between chemical
      administration and tumor incidence. Under the conditions of this bioassay, 1
      phenyl-2-thiourea was not carcinogenic to Fischer 344 rats or B6C3F1 mice.

PMID- 12799715
TI  - Bioassay of mexacarbate for possible carcinogenicity.
AB  - A bioassay of technical-grade mexacarbate for possible carcinogenicity was
      conducted using Osborne-Mendel rats and B6C3F1 mice. Mexacarbate was administered
      in the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The time-weighted average high and low dietary
      concentrations of mexacarbate were 418 and 209 ppm for male rats, 678 and 339 ppm
      for female rats, 654 and 327 ppm for male mice and 135 and 68 ppm for female
      mice. After a 78-week period of chemical administration, observation of rats
      continued for an additional 33 to 34 weeks and observation of mice continued for
      14 to 15 additional weeks. For each species, 20 animals of each sex were placed
      on test as controls. All groups except the male control mice survived
      sufficiently long to be at risk from late-appearing tumors. Because of poor
      survival of the male control mice, a pooled control group was used for
      statistical analysis of tumor incidence in male mice. The possibility that female
      mice in this study did not receive maximum tolerated dosages of mexacarbate
      should be considered. Administration of mexacarbate had no significant effect on
      survival or body weights of female mice. No neoplasms occurred in statistically
      significant increased incidences when dosed rats were compared to controls. Among
      male mice surviving at least 56 weeks, significant associations with dietary
      concentrations were indicated by the Cochran-Armitage test for hepatocellular
      carcinomas, for subcutaneous fibrosarcomas and for fibromas of the skin. In none
      of these cases, however, were these results supported by significant Fisher exact
      tests. Under the conditions of this bioassay, sufficient evidence was not
      obtained for the carcinogenicity of mexacarbate for Osborne-Mendel rats or B6C3F1
      mice.

PMID- 12799716
TI  - Bioassay of nithiazide for possible carcinogenicity.
AB  - The bioassay of nithiazide for possible carcinogenicity was conducted using
      Fischer 344 rats and B6C3F1 mice. Nithiazide was administered in the diet, at
      either of two concentrations, to groups of 50 male and 50 female animals of each
      species. The high and low concentrations of nithiazide utilized were,
      respectively, 1,250 and 625 ppm for rats and 5,000 and 2,500 ppm for mice. Dosed
      rats received feed containing nithiazide for 38 weeks, and as a result of a
      shortage of nithiazide, the animals were not fed the dosed feed for the next 9
      weeks. The dosed feed diet was then resumed and continued for 56 weeks, after
      which time a 1-week observation period followed. Dosed mice received feed
      containing nithiazide for 61 weeks and, due to a shortage of nithiazide, the
      animals were not fed dosed feed for the next 9 weeks. The dosed feed diet was
      then resumed and continued for 33 weeks, followed by a 1-week observation period.
      Twenty animals of each sex and species were placed on test as controls. In both
      species, adequate numbers of animals survived sufficiently long to be at risk
      from late-developing tumors. There was no significant positive association
      between dosage and mortality for either rats or mice. Compound-related mean body
      weight depression occurred in both sexes of each species. Statistically
      significant incidences of hepatocellular adenomas and carcinomas were found in
      high dose male mice but not in female mice. Although the increased incidences of
      these tumors in dosed female mice were not statistically significant, the
      evidence presented was strongly suggestive of carcinogenicity to the liver in
      female B6C3F1 mice. Statistically significant increased incidences of a
      combination of mammary and skin fibroadenomas and cystadenomas NOS were found in
      the high dose female rats. No unusual tumors were observed in either species.
      Under the conditions of this bioassay, nithiazide was carcinogenic in male and
      probably female B6C3F1 mice, causing a combination of hepatocellular carcinomas
      and hepatocellular adenomas. Nithiazide was also carcinogenic in female Fischer
      344 rats, causing an increase in the incidence of mammary neoplasms. The compound
      was not carcinogenic in male Fischer 344 rats.

PMID- 12799717
TI  - Bioassay of 3-chloro-p-toluidine for possible carcinogenicity.
AB  - A bioassay for the possible carcinogenicity of 3-chloro-p-toluidine was conducted
      using Fischer 344 rats and B6C3F1 mice. 3-Chloro-p-toluidine was administered in
      the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. Twenty animals of each sex and species were placed on
      test as controls. The time-weighted average dietary concentrations of 3-chloro-p
      toluidine administered to rats of both sexes were 3,269 and 1,635 ppm for the
      high and low dose groups, respectively. The high and low dietary concentrations
      of 3-chloro-p-toluidine administered to mice were, respectively, 1,200 and 600
      ppm for males and 600 and 300 ppm for females. The compound was administered in
      the diet for 78 weeks, followed by an observation period of 24 weeks for high
      dose male rats, 25 weeks for all other dosed rats, and 12 weeks for mice. There
      were no significant positive associations between the concentrations of 3-chloro
      p-toluidine administered and mortality in either species. Adequate numbers of
      animals in all groups survived sufficiently long to be at risk from late
      developing tumors. Mean body weight depression, relative to controls, was
      observed in high dose rats and mice of both sexes, indicating that the
      concentrations administered to these animals may have approximated the maximum
      tolerated dosages. The unusual incidences of nonneoplastic spleen and liver
      lesions in high dose rats supports this assumption. Under the conditions of this
      bioassay there was no convincing evidence for the carcinogenicity of 3-chloro-p
      toluidine in Fischer 344 rats or B6C3F1 mice.

PMID- 12799718
TI  - Bioassay of 2-aminoanthraquinone for possible carcinogenicity.
AB  - A bioassay of 2-aminoanthraquinone for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 2-Aminoanthraquinone was administered in
      the feed, at either of two concentrations (except for female rats), to groups of
      50 male and 50 female animals of each species. The time-weighted average dietary
      concentrations used in the chronic bioassay were 0.69 and 0.35 percent for high
      and low dose male rats, respectively, 0.2 percent for the treated female rats,
      and 1.0 and 0.5 percent, respectively, for high and low dose mice of both sexes.
      After a 78-week period of chemical administration (80 weeks for high dose mice),
      observation of the rats continued for up to an additional 32, weeks and
      observation of the mice continued for up to an additional 16 weeks. In both
      species adequate numbers of animals in all groups, except the treated female
      rats, survived sufficiently long to be at risk from late-developing tumors. The
      survival among treated female rats was poor and, as a result, no conclusions
      could be made regarding the carcinogenicity of the compound in these animals.
      When male rats having either hepatocellular carcinomas or neoplastic nodules of
      the liver were combined and the resulting tumor incidences were analyzed
      statistically, there was a significant positive association between dosage and
      the incidences of these combined neoplasms. Hepatocellular carcinomas were
      observed at significantly higher incidences when dosed mice were compared to
      controls. There was a significantly higher incidence of malignant hematopoietic
      lymphomas in high dose female mice when compared to controls. Under the
      conditions of this bioassay, dietary administration of 2-aminoanthraquinone was
      carcinogenic in male Fischer 344 rats, causing a combination of hepatocellular
      carcinomas and neoplastic nodules of the liver. The compound was also
      carcinogenic in B6C3F1 mice, causing hepatocellular carcinomas in both sexes and
      malignant hematopoietic lymphomas in females.

PMID- 12799719
TI  - Bioassay of 1,5-naphthalenediamine for possible carcinogenicity.
AB  - A bioassay of 1,5-naphthalenediamine for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. 1,5-Naphthalenediamine was administered
      in the feed, at either of two concentrations, to groups of 50 male and 50 female
      animals of each species. The high and low dietary concentrations utilized in the
      chronic bioassay were, respectively, 0.1 and 0.05 percent for rats and 0.2 and
      0.1 percent for mice. The compound was administered in the diet for 103 weeks,
      followed by up to 4 weeks of observation. Fifty mice of each sex and 25 rats of
      each sex were placed on test as controls. These animals were observed for up to
      110 weeks. There were no significant positive associations between the
      administered concentrations of 1,5-naphthalenediamine and mortality in either sex
      of rats or mice. In all groups adequate numbers of animals survived sufficiently
      long to be at risk from late-developing tumors. Among dosed female rats, a
      statistically significant increase in endometrial stromal polyps was observed.
      Several of these tumors underwent malignant transformation to endometrial stromal
      sarcomas. The incidence of female rats having either adenoma or carcinoma of the
      clitoral gland was statistically significant. No neoplasms were observed at
      significantly increased incidences in dosed male rats. Based on lack of clinical
      signs or weight loss, the male rats may have been able to withstand a higher
      dose. In mice, dose-related increases in thyroid neoplasms were observed in both
      sexes. The incidence of thyroid C-cell carcinomas was significant for high dose
      female mice. The combined incidences of papillary adenomas, follicular-cell
      adenomas and papillary cystadenomas of the thyroid were significant for mice of
      both sexes. The incidence of hepatocellular carcinomas and the incidence of
      alveolar/bronchiolar adenomas were each significant for dosed female mice. Under
      the conditions of this bioassay, 1,5-naphthalenediamine was carcinogenic in
      female Fischer 344 rats, causing clitoral and uterine neoplasms. 1,5
      Naphthalenediamine was also carcinogenic for B6C3F1 mice, producing thyroid
      neoplasms in males and neoplasms of the thyroid, liver, and lung in females.
      Insufficient evidence was provided for the carcinogenicity of the compound in
      male Fischer 344 rats.

PMID- 12799720
TI  - Bioassay of p-cresidine for possible carcinogenicity.
AB  - A bioassay of p-cresidine for possible carcinogenicity was conducted using
      Fischer 344 rats and B6C3F1 mice. p-Cresidine was administered in the feed, at
      either of two concentrations, to groups of 50 male and 50 female animals of each
      species. The dietary concentrations used in the chronic bioassay for low and high
      dose rats were 0.5 and 1.0 percent, respectively. The time-weighted average
      concentrations fed to low dose male, low dose female, high dose male and high
      dose female mice were 0.22, 0.22. 0.46, and 0.44 percent, respectively. All dosed
      animals, except for high dose male mice, were administered p-cresidine in the
      diet for 104 weeks and observed for an additional period of up to 2 weeks. All
      high dose male mice were dead by the end of week 92. For each species, 50 animals
      of each sex were placed on test as controls and fed only the basal laboratory
      diet. Mortality rates were dose-related for both sexes of both species. That
      incidences of certain tumors were higher in low dose than in high dose groups was
      probably due to accelerated mortality in the high dose group. In dosed rats of
      both sexes, statistically significant incidences of bladder carcinomas (combined
      incidences of papillary carcinomas, squamous-cell carcinomas, transitional-cell
      papillomas, transitional-cell carcinomas, and undifferentiated carcinomas) and
      olfactory neuroblastomas were observed. The combined incidence of neoplastic
      nodules of the liver, hepatocelular carcinomas, or mixed hepato/cholangio
      carcinomas was also significant in low dose male rats. In both male and female
      dosed mice, the incidence of bladder carcinomas (combined incidence of carcinomas
      NOS, squamous-cell carcinomas, and transitional carcinomas) was significant. The
      incidence of hepatocellular carcinomas was also significant in dosed female mice.
      Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer
      344 rats, causing increased incidences of carcinomas and of papillomas of the
      urinary bladder in both sexes, increased incidences of olfactory neuroblastomas
      in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in
      B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and
      hepatocellular carcinomas in females.

PMID- 12799721
TI  - Bioassay of 1-phenyl-3-methyl-5-pyrazolone for possible carcinogenicity.
AB  - A bioassay of 1-phenyl-3-methyl-5-pyrazolone for possible carcinogenicity was
      conducted using Fischer 344 rats and B6C3F1 mice. 1-Phenyl-3-methyl-5-pyrazolone
      was administered in the feed, at either of two concentrations, to groups of 49 or
      50 male and 50 female animals of each species. The high and low concentrations of
      1-phenyl-3-methyl-5-pyrazolone utilized were, respectively, 5,000 and 2,500 ppm
      for rats and 15,000 and 7,500 ppm for mice. Twenty animals of each species and
      sex were placed on test as controls. After a 103-week period of chemical
      administration, there was an additional observation period of 2 weeks for rats. A
      102-week period of chemical administration was followed by an additional 2-week
      observation period for mice. In both species adequate numbers of animals survived
      sufficiently long to be at risk from late-developing tumors. Compound-related
      mean body weight depression was observed in mice, but not in rats. In addition,
      no significant accelerated mortality or other signs of toxicity were associated
      with the dietary administration of 1-phenyl-3-methyl-5-pyrazolone to rats;
      therefore, it is possible that the compound was not administered to rats at the
      maximum tolerated concentration. There were no tumors in either sex of rats or
      mice for which a significant positive association could be established between
      chemical administration and incidence. Under the conditions of this bioassay,
      there was no evidence for the carcinogenicity of 1-phenyl-3-methyl-5-pyrazolone
      to Fischer 344 rats or B6C3F1 mice.

PMID- 12799722
TI  - Bioassay of pivalolactone for possible carcinogenicity.
AB  - The bioassay of pivalolactone for possible carcinogenicity was conducted using
      Fischer 344 rats and B6C3F1 mice. Pivalolactone in water was administered by
      gavage, at either of two dosages, to groups of 50 male and 50 female animals of
      each species. The high and low dosages of pivalolactone utilized were,
      respectively, 300 and 150 mg/kg/day for rats and 150 and 75 mg/kg/day for mice.
      After a 103-week period of compound administration for rats and a 102-week period
      of compound administration for mice, rats were observed for 2 additional weeks
      and mice for 1 additional week. Twenty animals of each sex and species were
      placed on test as vehicle controls. There was no significant positive association
      between dosage and mortality for either rats or mice, and in both species,
      adequate numbers of animals survived sufficiently long to be at risk from late
      developing tumors. Compound-related mean body weight depression was not observed
      in either sex of either species. In addition, no adverse clinical signs were
      observed among dosed mice. This evidence, plus the relatively fast decomposition
      of pivalolactone in water, suggests the possibility that the animals, and in
      particular the mice, may have been able to tolerate a higher dose. Statistically
      significant incidences of squamous-cell papillomas and squamous-cell carcinomas
      of the forestomach were observed in rats but not in mice. No other rare or
      unusual tumors were observed in either species. Under the conditions of this
      bioassay, pivalolactone was found to be carcinogenic to both male and female
      Fischer 344 rats, producing squamous-cell carcinomas and squamous-cell papillomas
      of the forestomach. This study provided no evidence for the carcinogenicity of
      pivalolactone in B6C3F1 mice of either sex.

PMID- 12799723
TI  - Prospects for the medical management of abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) are a chronic degenerative disease with life
      threatening implications. While AAAs are thought to arise through a localized
      form of arterial wall injury superimposed on various predisposing factors, their
      natural history is one of progressive structural deterioration, gradual
      expansion, and eventual rupture. Pathologic processes contributing to the changes
      observed in AAAs include chronic inflammation, destructive remodeling of the
      extracellular matrix, and depletion of vascular smooth muscle cells. These
      changes result in progressive aortic dilatation accompanied by alterations in
      vessel geometry, redistribution of hemodynamic wall stresses, and diminished
      tensile strength. As outlined in this review, better understanding of the
      biological mechanisms underlying these changes will allow design of novel
      therapeutic strategies to suppress the process of aneurysmal degeneration.

PMID- 12799725
TI  - Local versus general anesthesia for carotid endarterectomy: report of 329 cases.
AB  - Since stroke is an important cause of morbidity and mortality, carotid
      endarterectomies are used frequently to reduce the risk of stroke and death.
      Unfortunately, an inherent risk of the carotid endarterectomy procedure is that
      surgery itself may result in stroke. At this point the question is which method
      of anesthesia, local or general, is better to protect and monitorize the brain
      function during cross-clamp period in carotid endarterectomies? In the authors'
      center, 365 carotid endarterectomies were applied to 329 patients between 1990
      and 2001; 165 operations were done under general anesthesia and the other 200
      operations were done under local anesthesia. These 2 groups, general (group I)
      and local anesthesia (group II), were studied retrospectively according to
      preoperative and postoperative data. In group I, the rate of major stroke was
      7.3%, but this rate was 1% in group II (p < 0.05). Intraoperative shunts were
      used in 50 (30.3%) operations of group I, but the usage of shunt was 8% (16
      operations) in group II (p < 0.0001). The hospitalization period was also much
      shorter in group II than in group I. The time of hospitalization was 4.1 +/-1.9
      days in group I and 2.4 +/-1.1 days in group II (p < 0.0001). In terms of cost
      analysis, the mean costs were 1007.14 dollars +/-135.71 dollars in group I and
      885.71 dollars +/-78.57 dollars in group II (p < 0.0001). In short, the local
      procedure was more cost-effective. As a result, in carotid endarterectomy
      procedures, the authors prefer local anesthesia to achieve better brain function
      monitoring and to reduce hospitalization time and cost.

PMID- 12799724
TI  - Duplex ultrasound imaging with an ultrasound contrast agent: the economic
      alternative to CT angiography for aortic stent graft surveillance.
AB  - The use of endovascular stent graft repair for aortic aneurysmal disease has
      become increasingly common, with the added requirement for close postoperative
      surveillance to detect the presence of endoleaks or graft migration. The most
      commonly used technique for surveillance is computed tomography (CT) angiography,
      with the need for intravenous contrast posing 1 limitation in those patients with
      renal dysfunction and the cost of this testing presenting an economic limitation.
      Early results of duplex imaging in the authors' Vascular Laboratory using an
      intravenous ultrasound contrast agent have shown sensitivity and specificity
      equivalent to those of CT angiography, with no evidence of any related morbidity.
      They have evaluated the cost effectiveness of using duplex ultrasound imaging as
      the primary surveillance technique for postoperative follow-up in aortic stent
      graft patients. Surveillance protocols now require that 8 follow-up examinations
      be performed in the first 3 years after stent graft placement. The charges for CT
      angiography in their institution average 2,779 dollars per study, for a 3-year
      total of 22,232 dollars per patient. The charges for aortic duplex ultrasound
      average 525 dollars per study, with a 3-year total of 4,200 dollars per patient.
      Adding the cost of routine abdominal radiographs to confirm stent graft position
      (147 dollars per study) would bring this 3-year total to 5,376 dollars, a savings
      of 16,856 dollars per patient. For every 100 patients who are followed up after
      stent graft placement, this represents a 3-year savings of more than 1.6M
      dollars. Promising early results of duplex ultrasound imaging with an intravenous
      contrast agent show sensitivity and specificity equivalent to those of CT
      angiography in detecting aneurysm size and graft endoleaks or other hemodynamic
      abnormalities. If these results can be demonstrated in larger patient series,
      this technique should become the method of choice for stent graft surveillance,
      for it offers very significant economic advantages and avoids the complications
      of intravenous contrast-induced renal dysfunction.

PMID- 12799726
TI  - Prediction of arteriovenous access steal syndrome utilizing digital pressure
      measurements.
AB  - Steal syndrome is a well-known complication of arteriovenous (AV) access
      placement. To assess the derangement in hemodynamics of the upper extremity after
      AV access creation, brachial and digital pressures were performed before and
      after operation. Thirty-five patients (ages 20-88 years) with end-stage renal
      disease requiring new upper extremity hemodialysis AV access were prospectively
      evaluated. Values were obtained preoperatively, on the day of surgery, and 1
      month postoperatively. Follow-up at 1 year was obtained on all patients. Of the
      35 patients, 19 (54%) were diabetic and 9 (26%) had had a prior AV access. The AV
      accesses created included the following: autogenous brachial-cephalic (n = 14,
      40%), autogenous radialcephalic (n = 10, 29%), brachial-basilic transposition (n
      = 5, 14%), prosthetic brachial-antecubital forearm loop (n = 3, 9%), autogenous
      brachial-axillary saphenous vein translocation (n = 2, 6%), and 1 (3%) prosthetic
      brachial-axillary. After AV access creation the digital brachial index (DBI)
      dropped in 28 (80%) of the 35 patients. Six patients (17%) developed a
      symptomatic steal, 3 of which (9%) eventually required revision. In those
      patients without ischemic steal symptoms (n = 29) the mean DBI decreased from 0.9
      to 0.7 (p < 0.01) immediately and decreased no further at 1 month. For those with
      a symptomatic steal the DBI decreased from 0.8 to 0.4 (p < 0.01) immediately and
      decreased no further at 1 month. Utilizing a DBI less than 0.6, the sensitivity
      was 100%, the specificity 76%, the positive predictive value 46%, and the
      negative predictive value 100%. Hemodynamic steal after AV access creation is
      very common, with symptomatic steal occurring nearly a fifth of the time.
      Utilizing digital pressure measurements, a DBI less than 0.6 obtained on the day
      of surgery can reasonably predict which patients are at risk for the development
      of a symptomatic steal.

PMID- 12799727
TI  - Arterial compromise caused by lower limb osteochondroma.
AB  - Osteochondromas occasionally cause arterial complications, mainly concerning the
      distal superficial femoral and popliteal arteries. The authors present 11
      patients (12 cases) with arterial disorders caused by exostoses who were
      hospitalized in their Vascular Clinic. All but 1 had signs or symptoms of
      peripheral arterial disease such as intermittent claudication or diminished
      peripheral pulses, and 1 also presented serious neurologic sequelae. All were
      examined by radiography, ankle-brachial index (ABI), computed tomography scan,
      color duplex scan, arteriography, and scintigraphy. The popliteal artery was the
      most commonly affected vessel in 7 cases. In addition to the removal of the
      offending osteochondroma, 7 patients underwent excision of the diseased arterial
      segment and replacement by a saphenous vein interposition graft. The remaining 5
      cases received a vein graft patch. The authors achieved good results with no
      serious complications detected in the immediate postoperative period and
      subsequent follow up. Surgical treatment of the vascular complications caused by
      exostoses is mandatory. Even in the absence of vascular symptoms, such bony
      lesions in close proximity to a vessel should be on a close follow-up in order to
      prevent permanent arterial damage.

PMID- 12799728
TI  - Dichloroacetate increases skeletal muscle pyruvate dehydrogenase activity during
      acute limb ischemia.
AB  - The purpose of this study was to evaluate the effects of dichloroacetate sodium
      (DCA), a drug that inactivates pyruvate dehydrogenase kinase (PDH-K), on pyruvate
      dehydrogenase (PDH) activity, lactate level, and function of skeletal muscle in
      an experimental model of acute limb ischemia. Thirty-two male Sprague-Dawley rats
      underwent right iliac artery ligation to produce hindlimb ischemia. After 2 hours
      of ischemia, 16 animals received intravenous DCA (15 mg/100 g body weight) and 16
      control animals received an equivalent volume of normal saline. After an
      additional 1 hour of ischemia (total 3 hours) tibialis anterior muscle from the
      ischemic limb and contralateral nonischemic limb was excised, rapidly freeze
      clamped with Wallenberg tongs cooled in liquid nitrogen, and stored at -70
      degrees C. Muscles specimens were subsequently assayed for PDH activity and
      lactate level by use of spectrophotometric techniques. An additional 16 animals
      (DCA-treated, n = 8; control, n = 8) underwent ex-vivo gastrocnemius muscle
      fatigue testing with a 10 g tension preload after 3 hours of limb ischemia. In
      ischemic hind limbs, DCA treatment significantly (p = 0.025) increased PDH
      activity (19.6 +/-1.6 micromol/min/g dry weight) compared to controls (13.1 +/
      1.3 micromol/min/g dry weight). DCA treatment did not increase (p = 0.13)
      skeletal muscle PDH activity in the nonischemic limbs (9.6 +/-1.1 micromol/min/g
      dry weight, controls; 13.2 +/-1.3 micromol/min/g dry weight, DCA group). In DCA
      treated animals, hind limb ischemia resulted in no significant increase in muscle
      lactate levels compared to the nonischemic limb, while control animals
      demonstrated a significant (p = 0.005) elevation in lactate level in ischemic
      limbs compared to contralateral nonischemic limb. Ischemia induced a significant
      decrease in time to muscle fatigue in both DCA-treated and control animals (p =
      0.002 and 0.001, respectively). Time to muscle fatigue in DCA-treated animals was
      increased compared to controls (2.6 +/-0.3 versus 2 +/-0.6 minutes; p < 0.05)in
      ischemic limbs but was not significantly different in nonischemic limbs (DCA =
      3.3 +/-0.5 minutes; control = 3.1 +/-0.6 minutes). Treatment with DCA during
      acute limb ischemia reduced the depression of PDH activity and lactate level of
      skeletal muscle. Ischemic muscle function was also improved by DCA treatment.
      Further investigation of the potential beneficial effects of DCA treatment on
      muscle injury during ischemia and reperfusion is warranted.

PMID- 12799729
TI  - Relationship of peripheral arterial compliance and standard cardiovascular risk
      factors.
AB  - Abnormalities of peripheral arterial compliance are clinically useful markers of
      atherosclerosis and risk of vascular events. Local peripheral arterial compliance
      can be easily and accurately assessed in the clinic by computer-controlled pulse
      volume recordings (air plethysmography). The purpose of this study was to
      investigate the relationship between clinical cardiovascular risk factors, a
      surrogate of atherosclerotic burden, and peripheral arterial compliance in the
      thigh and calf determined by quantification of local pulse volume recordings in
      patients undergoing coronary angiography. Peripheral arterial compliance in the
      thigh and calf was measured in 346 patients undergoing diagnostic cardiac
      catheterization at 4 centers. Demographic and cardiovascular risk factor data
      were collected, and their relationship to local arterial compliance examined
      using a new device that assesses maximal local arterial volume change in an
      extremity segment. Pulse volume recordings detected decreased local arterial
      compliance in the thigh associated with a history of hypertension (p < 0.0001),
      diabetes mellitus (p = 0.0001), and hyperlipidemia (p = 0.0007). In the calf,
      this arterial compliance measure was associated with a history of hypertension (p
      < 0.0001) and diabetes mellitus (p = 0.002). Females had lower arterial
      compliance than males in the thigh (p = 0.003) and calf (p < 0.0001). Limited
      evidence of lower arterial compliance in the thigh was found for those with
      obesity (p = 0.07). This procedure also demonstrated that subjects with multiple
      cardiovascular risk factors had lower arterial compliance in the thigh than
      subjects with no or 1 risk factor (p = 0.0001). Peripheral arterial compliance
      determined by air plethysmography is strongly associated with standard
      cardiovascular risk factors. The noninvasive measurement of local arterial
      compliance by regional pulse volume recording may be a useful adjunct for
      cardiovascular risk stratification early in the course of the disease as well as
      for monitoring vascular response to therapy.

PMID- 12799730
TI  - Adjunctive endovascular techniques in the management of postoperative carotid
      artery pseudoaneurysms--useful armamentarium for vascular surgeons--three case
      reports.
AB  - Postoperative carotid artery pseudoaneurysms are rare. The traditional treatment
      of choice has been operative repair, which can present a significant technical
      challenge owing to the reoperative neck inflammation and potential cranial nerve
      injuries. The authors report 3 cases of postoperative carotid pseudoaneurysms
      that were successfully managed by use of various adjunctive endovascular
      techniques. The adjunctive endovascular maneuvers included the following: 1)
      endoluminal balloon placement for preoperative test occlusion and intraoperative
      proximal control to facilitate operative dissection in the first patient with a
      carotid pseudoaneurysm; 2) endoluminal stent-graft placement to exclude a large
      expanding carotid pseudoaneurysm in the second patient; and 3) endoluminal coil
      placement along with balloon occlusion to achieve complete hemostasis in the
      third patient, who presented with a hemorrhaging carotid pseudoaneurysm.
      Successful outcomes were achieved in all 3 patients by use of adjunctive
      endovascular techniques. These cases underscore the role of adjunctive
      endovascular treatment as an armamentarium for vascular surgeons in the treatment
      of complex carotid pseudoaneurysms.

PMID- 12799731
TI  - Mycotic aneurysm of the internal carotid artery--a case report.
AB  - Extracranial internal carotid artery (ICA) mycotic aneurysms are rare entities
      that may result in significant neurologic morbidity and mortality. Several
      operative techniques have been described in the literature for the management of
      this difficult condition. This case report describes a contained ruptured mycotic
      aneurysm of the extracranial ICA associated with Proteus mirabilis infection
      successfully treated by an end-to-end spatulated interposition saphenous vein
      graft.

PMID- 12799732
TI  - Endovascular treatment of traumatic thoracic aortic rupture combined with
      diaphragmatic rupture--a case report.
AB  - The purposes of this report are to describe the immediate repair of a
      diaphragmatic rupture and subsequent endovascular treatment of a thoracic aortic
      rupture secondary to blunt chest and abdominal trauma and to discuss the outcome
      in the light of the trauma scores. A 29-year-old man was injured in a car
      collision. There were signs of a left diaphragmatic rupture and spleen injury.
      After urgent laparotomy, the diaphragm was repaired. The spleen appeared
      uninjured; however, there was a dissection with a transmural tear of the thoracic
      aorta, which was subsequently treated intraluminally by using a Talent
      endovascular graft and two AneuRx aortic extension cuffs. The patient fully
      recovered, and the thoracic endograft showed no evidence of endoleak both 1 month
      and 1 year after treatment. Fourteen months after the operation, the patient is
      doing well. Endoluminal techniques can be used successfully in the immediate
      repair of thoracic aortic injuries, even in the presence of a diaphragmatic
      rupture. With the introduction of advanced repair modalities, such as
      endovascular techniques, mortality rates will decrease and may eventually alter
      injury-scoring systems such as the Injury Severity Score.

PMID- 12799733
TI  - Leiomyosarcoma of the inferior vena cava--a case report.
AB  - This paper presents a patient successfully treated for leiomyosarcoma of the vena
      cava, with no recurrence or symptoms on an 8-year follow-up. A 56-year-old woman
      presented with chronic and progressive periumbilical and right upper abdominal
      pain. Physical examination and laboratory tests revealed no abnormalities.
      Computed tomography showed a high-density image inside the vena cava. Cavography
      showed a filling defect with complete occlusion of the vena cava involving the
      renal veins and greatly developed collateral circulation through lumbar veins.
      Laparotomy was performed and a large caval mass involving the renal veins was
      dissected and resected. Venous reconstruction was undertaken using a 19-mm bovine
      pericardium prosthesis (Labcor, MG-Brazil) interposed as a substitute to the vena
      cava, and the renal veins were anastomosed to the side of the graft. Pathologic
      examination confirmed a leiomyosarcoma with free surgical margins. The
      postoperative course was uneventful and the patient was discharged on
      postoperative day 8. The venous flow through the inferior vena became normal, as
      confirmed by later cavography. This paper presents a case of successfully managed
      leiomyosarcoma of the vena cava with a thorough review of the literature. The
      treatment of such patients and the use of bovine pericardium are also discussed.

PMID- 12799734
TI  - Regarding "routine early postoperative duplex scanning is unnecessary following
      uncomplicated carotid endarterectomy".

PMID- 12799736
TI  - The PIVKA II test: the first reliable coagulation test for autopsy
      investigations.
AB  - To date there is no routinely used reliable diagnostic test that can be performed
      in the post-mortem period to investigate whether a deceased had a coagulation
      disorder. This paper describes a series of experiments to assess the use of an
      antigen-based method to investigate the vitamin K-dependent factor II function in
      the deceased. It illustrates that by using this approach the functional status of
      factor II can be investigated in the post-mortem period. The abnormal proteins
      that are investigated by this method appear to remain stable for at least 72 h
      and potentially up to at least 7 days. The method that is illustrated could thus
      be reliably used in the post-mortem period to identify a natural or drug-induced
      factor II abnormality. The potential for other protein components of the
      coagulation cascade to be investigated by similar antigen-based methodology is
      suggested.

PMID- 12799738
TI  - Mitochondrial DNA heteroplasmy or artefacts--a matter of the amplification
      strategy?
AB  - We compared two different PCR strategies for the amplification of mtDNA
      hypervariable region 1 (HV1) with regard to the detection and interpretation of
      point mutation heteroplasmy in human hair roots. We monitored the level of
      detected heteroplasmy using direct sequence analysis. PCR amplifications were
      performed in duplicate on each hair root, using 62 cycles of nested PCR versus 35
      cycles of direct PCR. As a previous publication reported different sensitivities
      of heteroplasmy detection based on the number of PCR cycles used, we were
      interested in whether and how different PCR amplification strategies would impact
      sequence quality and the detection of point heteroplasmy. We identified 12 out of
      93 hair roots as heteroplasmic (7 out of 31 persons) with direct PCR, whereas 2
      of these heteroplasmic events could not be identified with the nested PCR
      approach. Generally, the quality of the sequence electropherograms in terms of
      background noise was significantly lower for the nested PCR amplification
      strategy, leading to ambiguous results in some of the nucleotide positions. Thus,
      the ability to clearly distinguish a genuine mixture of two nucleotides from
      background noise at a heteroplasmic position was substantially greater with
      direct PCR amplification, which generally resulted in higher quality sequence
      electopherograms.

PMID- 12799737
TI  - Protamine mRNA as molecular marker for spermatozoa in semen stains.
AB  - Cytological detection of spermatozoa with subsequent DNA analysis is the most
      important biological evidence in sexual crimes when suitable samples are
      available. Immunological and enzymatic detection of semen-specific proteins may
      be helpful but cannot replace specific identification of spermatozoa. We have
      recently shown that detection of cell-specific gene expression can be used to
      identify menstrual blood. In this paper we demonstrate that the basic
      nucleoproteins protamine 1 and 2 are suitable markers for spermatozoa because
      they are exclusively expressed in the haploid genome and that protamine mRNA can
      be detected in semen stains by the highly sensitive reverse transcriptase
      polymerase chain reaction (RT-PCR). With semi-nested PCR, 10-100 spermatozoa are
      theoretically sufficient to provide positive amplification results, with hot
      start PCR at least 100-1,000 cells are required corresponding to an average semen
      volume of 0.01-0.1 microl. This new method thus allows specific identification of
      spermatozoa with molecular biology tools and may broaden the spectrum of
      investigations in the forensic laboratory.

PMID- 12799739
TI  - New sensitive amplification primers for the STR locus D2S1338 for degraded
      casework DNA.
AB  - PCR primers for the locus D2S1338 were redesigned in order to reduce the length
      of the amplification product compared with the conventional design. The new
      amplification primers were applied to highly degraded casework samples, which
      gave no or only weak results for D2 in previous analyses. The application of the
      new primers resulted in an increased overall typing success rate. In a
      concordance study between the conventional and the newly designed primers, no
      genotype differences were revealed in 503 randomly selected individuals. This
      suggests robust amplification conditions with respect to mutation-based allele
      drop-out.

PMID- 12799742
TI  - Notes on antipsychiatry.
AB  - The present paper aims to provide a review of the history and basic principles of
      the antipsychiatric movement, as well as to discuss the work of its most
      important theorists. The authors searched recent literature, as well as drawing
      upon some of the basic antipsychiatric texts. Antipsychiatry emerged as an
      international movement during the 1960s as part of the historic tumult of the
      period rather than as a result of the evolution of scientific ideas.
      Antipsychiatrists radically opposed what they understood as a hospital-centered
      medical specialty legally empowered to treat and institutionalize mentally
      disordered individuals. Indeed, many antipsychiatrists argued against the very
      existence of mental disorders themselves. After the 1970s, the antipsychiatry
      movement became increasingly less influential, due in particular to the rejection
      of its politicized and reductionistic understanding of psychiatry.

PMID- 12799743
TI  - Is the antidepressive effect of sleep deprivation stabilized by a three day phase
      advance of the sleep period? A pilot study.
AB  - Sleep deprivation (SD) induces a rapid amelioration of mood in about 60 % of
      depressed patients. After the next night of sleep, however, most patients
      experience a relapse. Previous studies demonstrated that a six day sleep-phase
      advance protocol prevents relapses in about 60 % of patients who responded
      positively to SD. We investigated whether also a three day phase advance of the
      sleep period might be able to maintain the antidepressant effects of SD. Twenty
      eight medicated depressed inpatients, who had a significant improvement after a
      SD in one night were recruited for this study. The phase advance protocol began
      on the first day after SD with a bed time from 5:00 p. m. to 12:00 p. m. on the
      first, from 7:00 p. m. to 2:00 a. m. on the second and 9:00 p. m. to 4:00 a. m.
      on the third day after SD. Three patients dropped out because of protocol
      violations. Only ten of the remaining 25 SD responders had a relapse during the
      three days of phase advance treatment or during the two days after it. Two of the
      relapsers improved again until day 6, i. e. 68 % showed an improvement of at
      least 30 % six days after the beginning of the treatment. This study indicates
      that even a three day phase advance protocol may help to prevent relapses after
      successful SD.

PMID- 12799744
TI  - Psychopathological dimensions in first-episode psychoses. From the trunk to the
      branches and leaves.
AB  - BACKGROUND: Dimensional frameworks for structuring psychopathology have been
      formulated in recent years to overcome classification problems of categorical
      approaches. However, few studies have addressed the dilemma of hierarchy within
      symptoms or dimensions in psychosis. METHODS: This study was designed to examine
      the hierarchical structure of psychopathological dimensions in first episode
      psychosis. The sample consisted of 94 first-episode patients psychosis. An
      exhaustive psychopathological assessment was carried out using the AMDP-system.
      Consecutive principal component analyses of AMDP symptoms, determining 'a priori'
      the number of factors to be extracted, were carried out. RESULTS: Following the
      track of the resulting factor analyses, a 'vertical hierarchical' framework was
      achieved. Our schema organized dimensions in a series of echelons in which lower
      tiers are subsumed as subsets of those assigned to higher ranks. In addition, a
      final model comprising 10 dimensions provided an 'horizontal' and
      multidimensional structure comprising all relevant psychopathological dimensions
      in first-episode psychosis. CONCLUSIONS: This study confirmed to a great extent
      the existence of a hierarchical organization within psychopathological dimensions
      in 'first-episode' psychosis. The present 'hierarchical and multidimensional'
      model of psychopathological dimensions allows for selection of the level of
      complexity of 'candidate phenotypes' to use in neurobiological research of
      psychosis.

PMID- 12799745
TI  - Alterations in brain activation in posttraumatic stress disorder patients with
      severe hyperarousal symptoms and impulsive aggressiveness.
AB  - OBJECTIVE: We wanted to assess possible alterations in brain activation in PTSD
      patients with severe hyperarousal symptoms and impulsive aggressiveness. METHOD:
      25 Croatian War (1991-1995) veterans with combat-related PTSD with severe
      hyperarousal symptoms and impulsive aggressiveness were assessed for possible
      alterations in cerebral blood flow in single photon emission computed tomography
      brain scans. RESULTS: Increased regional cerebral blood flow in projection area
      of nucleus accumbens was found in 13 of 25 subjects, and for all in the dominant
      brain hemisphere. DISCUSSION: We believe that at least some of PTSD symptoms, and
      especially the impulsive aggression, can be associated with increased regional
      cerebral blood flow in the projection area of nucleus accumbens.

PMID- 12799746
TI  - Premorbid IQ and schizophrenia. Increasing cognitive reduction by episodes.
AB  - In order to test the hypothesis that acute schizophrenia episodes have a negative
      impact on cognitive function, 35 consecutive non-abuse schizophrenia outpatients
      (age < 60) were enrolled in this study. All subjects for whom grades from the
      9(th) year of the Swedish school system were available, had to complete a
      comprehensive computerized neuropsychological test session. Symptoms were rated
      by PANSS and GAF, previous episodes were tallied, and medication was logged. A
      premorbid cognitive score was calculated on the basis of school grades and
      validated by comparison with academic career and current cognitive performance (r
      = 0.56). Half had college level studies or higher, and the overall school grades
      for the group were above average. PANSS (sum = 59) and GAF [59] ratings as well
      as medication (M = 230 CPZ units) suggested a moderate symptom level. Two
      patients had no neuroleptic drugs, 16 had atypical and 17 had conventional
      neuroleptics. Vocabulary was intact. On average, patients had lost 1 standard
      deviation (SD) in most cognitive tests but response time slowing amounted to 3.5
      SD. There were no differences in cognition between drug types and no correlation
      with CPZ dose. The number of previous episodes was positively correlated with
      reaction time prolongation and negatively correlated with short-term verbal
      memory, consistent with a previous study suggesting that acute episodes cause
      specific cognitive reduction.

PMID- 12799747
TI  - Free radicals in patients with post-traumatic stress disorder.
AB  - There is mounting evidence indicating that reactive free radical species (FRs)
      are involved in initiation and development of many different forms of human
      pathologies including psychiatric disorders. In the present study, we aimed to
      determine whether antioxidant enzyme (glutathione peroxidase, GSH-Px; superoxide
      dismutase, SOD and catalase, CAT) activities and malondialdehyde (MDA) levels, a
      product of lipid peroxidation, were associated with post-traumatic stress
      disorder (PTSD). The study comprised 14 patients who had been diagnosed with PTSD
      according to DSM-IV criteria and met the admission criteria and 14 healthy
      controls. The activities of GSH-Px SOD, CAT and MDA were measured in both the
      patients and controls. In addition, all patients were assessed using the
      Clinician Administered PTSD Scale (CAPS). The mean GSH-Px, SOD, CAT activities
      and MDA levels of the patient group did not differ from those of the controls.
      However, in patients, the GSH-Px and SOD activities were significantly and
      positively correlated with CAPS scores, while there was a trend toward positive
      correlations between CAPS scores and MDA or CAT. In conclusion, our results
      suggest that the production of FRs does not seem to be related to PTSD.

PMID- 12799749
TI  - Cerebrospinal fluid tau protein levels in schizophrenia.
AB  - Increased cerebrospinal fluid (CSF) tau protein levels are generally considered
      to provide a sensitive marker of neurodegenerative processes such as Alzheimer's
      disease (AD). Since a more pronounced cognitive decline has been described in
      older schizophrenic patients, it has been hypothesized that these patients might
      be at a higher risk of developing AD. CSF levels of total tau protein and tau
      protein phosphorylated at threonine 181 (phospho-tau) were determined among 19
      older and younger patients with schizophrenia compared to 20 age-matched healthy
      controls. No significant differences in CSF total tau and phospho-tau levels
      arose between patients with schizophrenia and controls. Although our results do
      not exclude a progressive neurodegenerative pathology, they provide evidence
      against major neuronal degeneration such as an AD-related pathology associated
      with increased tau levels in schizophrenia.

PMID- 12799748
TI  - Influence of genetic loading, obstetric complications and premorbid adjustment on
      brain morphology in schizophrenia: a MRI study.
AB  - Cerebrospinal fluid (CSF) space enlargement in schizophrenia is a prominent
      finding. This study was initiated to examine the influence of genetic loading,
      obstetric complications and premorbid adjustment on the extent of this
      enlargement. The sample of this MRI study consisted of 40 schizophrenic patients,
      24 psychiatric and 40 healthy family members from 10 uniaffected and 19 multiple
      affected families with schizophrenia, such as 27 control subjects from non
      affected families. The ventricle-to-brain-ratio (VBR), and the areas of the third
      ventricle, sylvian fissure, temporal horn and interhemispheric fissure at the
      slice where these structures reached their maximum were examined relatively to
      the corresponding total brain areas. The sum of CSF areas was calculated as a
      parameter for global atrophy. From MANCOVA adjusted for intervening variables the
      right VBR and the sum of CSF areas revealed significant differences between
      diagnostic groups. For these areas schizophrenic patients showed an increase
      compared to control subjects and family members with psychiatric disorder.
      Genetic loading influenced the interhemispheric fissure, enlarged in multiple
      affected compared to uniaffected families, and the temporal horn asymmetry, which
      was right sided (right > left) in control subjects and multiple affected
      families, but inverted in uniaffected families. Neonatal obstetric complications
      influenced only the size of the VBR, while premorbid adjustment predicted various
      CSF areas. In conclusion, schizophrenic subjects from multiple and uniaffected
      families showed a global atrophy, which was most pronounced in the VBR. Genetic
      loading seems to have an impact on frontal regions as the interhemispheric
      fissure and on the temporal horn.

PMID- 12799750
TI  - Antidepressant efficacy of two different rTMS procedures. High frequency over
      left versus low frequency over right prefrontal cortex compared with sham
      stimulation.
AB  - BACKGROUND: This placebo-controlled study was designed to investigate the
      influence of two different stimulation procedures of repetitive transcranial
      magnetic stimulation (rTMS) on depressive symptoms in patients with depressive
      disorders. Furthermore, effects on cognitive functions and psychomotor
      functioning were tested. METHODS: Thirty patients with depression (22 females and
      8 males; mean age of 56.4 years) were included. They were treated with a stable
      dosage of antidepressant medication. They received either high frequency rTMS (20
      Hz) over the left dorsolateral prefrontal cortex (LDLPFC), low frequency rTMS (1
      Hz) over the right dorsolateral prefrontal cortex (RDLPFC) or sham stimulations
      (10 patients in each group) as add on treatment at 10 days within 2 weeks.
      Depressive symptoms were registered by means of observer ratings (Hamilton
      Depression Rating Scale - HDRS) and self reports (Beck Depression Inventory -
      BDI). Psychomotor retardation was investigated by the Motor Agitation and
      Retardation Scale and cognitive function by d2 test. RESULTS AND CONCLUSIONS:
      Differences between the rTMS procedures regarding depressive symptoms could not
      be found. Motor abnormalities, however, significantly improved exclusively after
      real stimulation procedures. Patients with less severe deficits in psychomotor
      speed and concentration responded more intensively than patients with severe
      deficits.

PMID- 12799751
TI  - Challenges of teaching surgery: ethical framework.
AB  - Surgeons, trainees, and patients may be uncomfortable with the secrecy that
      surrounds the process of teaching and learning surgical procedures. Well
      structured training programs use a system of graded responsibility, supervision,
      and evaluation to ensure skill development and patient safety. Patient outcomes
      are generally excellent in training institutions. Disclosure of the role of
      trainees and their contribution to care enhances trust.

PMID- 12799753
TI  - Ethics curricula in surgery: needs and approaches.
AB  - Surgeons practice an intense form of applied ethics. The growing complexity of
      medical and surgical interventions combined with reduced opportunity to serve as
      ethical role models for trainees necessitates formal ethics curricula in surgery
      and the development of continued ethics education for surgeons through all stages
      of their careers. The Royal College of Physicians and Surgeons of Canada and the
      American College of Surgeons ethics curricula provide practical methods for
      dealing with the ethical issues that confront surgical residents each day. We can
      improve and expand upon curricula for surgical residents by taking into
      consideration the evolutionary stages of life of a surgeon: the pre-surgeon, the
      medical student, the beginning resident, the midlevel resident, the senior
      resident, the young to midlevel surgeon, and the advanced surgeon.

PMID- 12799752
TI  - Patient safety in surgery: error detection and prevention.
AB  - Error in medicine is becoming a well recognized phenomenon. The U.S. Institute of
      Medicine's publication in 1999 included estimations that medical error is the
      eighth leading cause of death in the United States and results in up to 100,000
      deaths annually. Retrospective studies and a few prospective studies are shedding
      more light on this challenging problem. Strategies to reduce error and increase
      patient safety have not been widely developed or embraced by surgeons for a
      variety of reasons. We provide a review on patient safety aimed at surgeons that
      includes definitions, incidence of errors including those in the surgical
      literature, causes of error, methods of error detection, and strategies to
      minimize errors and maximize patient safety.

PMID- 12799754
TI  - Operative treatment of mid-shaft clavicular non-union.
AB  - Between 1974 and 1999, we treated operatively 28 patients with a symptomatic mid
      shaft clavicular non-union using AO osteosynthesis, including bone grafting. Nine
      patients had a wave-plate osteosynthesis and 19 a standard AO/ASIF
      osteosynthesis. The mean follow-up was 10 (2-25) years. All but one non-union
      showed full bony consolidation. Pre-operatively, brachialgia was present in 12
      patients. Of these patients, six were treated using standard osteosynthesis
      technique and six by wave-plate osteosynthesis. Post-operatively, patients
      treated by wave-plate osteosynthesis had no brachialgia and also had a higher
      Constant score than those patients treated using standard AO/ASIF techniques.

PMID- 12799755
TI  - Limb salvage for malignant bone and soft-tissue tumours of the shoulder girdle.
AB  - We treated 15 patients with malignant bone and soft-tissue tumours of the
      shoulder girdle using limb salvage operations involving resection of the proximal
      humerus, scapula and clavicle. The oncological and functional outcomes were
      evaluated in all patients after an average of 5 (1-13) years. Oncological
      evaluation revealed that in 11 patients with adequate surgical margins six were
      continuously disease free and two had no evidence of disease. Three patients with
      marginal surgical margins had all died. We suggest that only where adequate
      surgical margins can be obtained should operations be performed. Forequarter
      amputation is still indicated in patients with complicated neurovascular
      involvement. Functional evaluation showed that scapular resections, especially
      glenoid resections, provided poor results (mean score 54%) in comparison with
      patients without such resection (mean score 82%).

PMID- 12799756
TI  - Femoral shaft fractures in children--a comparison of treatment.
AB  - Between April 1986 and March 1997, 83 femoral-shaft fractures in children 4-8
      years old were treated at Christian Medical College and Hospital, Ludhiana,
      India. Among 35 patients with a minimum of 12 months follow-up, 14 were treated
      with Hamilton-Russell (HR) skin traction and 14 with proximal tibial skeletal
      traction. The group treated with HR traction had a shorter duration of (a)
      hospital stay (average 16.8 days versus 29.7 days for skeletal traction, p=0.02),
      (b) time to fracture consolidation (average 8.8 weeks versus 10.8 weeks for
      skeletal traction, p=0.04), and (c) return to normal activities (average 12.2
      weeks versus 17.2 weeks for skeletal traction, p=0.03). At final follow-up
      (minimum 1 year), there were no significant differences in functional outcomes.
      Conservative management is still a gold standard for treatment of closed femoral
      shaft fractures in children 4-8 years of age. There appears to be no advantage to
      skeletal traction over skin traction in this age group.

PMID- 12799757
TI  - Traction spica cast for femoral-shaft fractures in children.
AB  - We treated 20 children for an isolated femoral shaft fracture using distal tibial
      traction incorporated into a spica cast with the knee in full extension. Patients
      were discharged from the hospital at a mean of 5.1 days following injury. All
      fractures healed, and there were four minor complications. At a mean follow-up of
      35 (13-72) months, all patients were asymptomatic with normal function. All but
      one fracture healed in acceptable alignment, and there was no clinically
      significant leg-length discrepancy. The method is relatively simple to employ and
      may be advantageous in a setting of limited resources.

PMID- 12799758
TI  - Treatment of transient bone marrow oedema of the hip--a comparative study.
AB  - Between 1990 and 2000, we treated 43 patients with transient bone marrow oedema
      of the hip. Five were treated with nonsteroidal antiinflammatory drugs (NSAIDs)
      and limited weight bearing, and 38 by core decompression followed by limited
      weight bearing. At follow-up 2-10 years later, all patients were assessed by a
      structured interview as well as the Harris hip score (HHS) and the Western
      Ontario and MacMaster Universities Osteoarthritis Index (WOMAC). Both groups
      reached the same clinical outcome (HHS and WOMAC). Core decompression enabled a
      significantly faster recovery. There were no complications, but progression to
      avascular necrosis was seen in both groups. Core decompression induced fast pain
      relief, making it the preferable treatment.

PMID- 12799759
TI  - Risk of amputation following limb salvage surgery with endoprosthetic
      replacement, in a consecutive series of 1261 patients.
AB  - Endoprosthetic replacements are commonly used for limb salvage following surgical
      excision of bone tumours. Advantages include initial reliability, rapid
      restoration of function and their ready availability. Potential long-term
      problems include loosening, infection and mechanical failure. Increasing problems
      may lead to the necessity for amputation; this paper assesses that risk. A total
      of 1,261 patients have undergone endoprosthetic replacements in our centre in the
      past 34 years, with a total of 6,507 patient years of follow up. A total of 112
      patients have had subsequent amputation. The reasons for amputation were local
      recurrence in 71, infection in 38, mechanical failure in two and chronic pain in
      one. The proximal tibia had the greatest risk of amputation (n=38/245). The time
      to amputation varied from 2 days to 16 years, with a mean of 31 months. The risk
      of amputation decreased with time, although 10% took place after more than 5
      years.

PMID- 12799760
TI  - Duplex ultrasonography after total hip or knee arthroplasty.
AB  - We prospectively studied all patients admitted for total hip (THR) or knee (TKR)
      arthroplasty from July 2000 to February 2001. No pharmacological anticoagulation
      was given. All patients received a standardized postoperative rehabilitation
      regimen. Forty-six patients with known risk factors for deep vein thrombosis
      (DVT) were excluded. Eighty patients were studied (22 THR, 58 TKR; 55 women, 25
      men). Mean age was 68 (30-90) years. Duplex ultrasonography on both lower limbs
      was performed on days 5-7 postoperatively. Location and extent of any thrombus
      were documented. In patients with distal DVT, a follow-up scan was done on days
      10-14. If proximal propagation was observed, patients received full
      anticoagulation. If no propagation was detected, the distal thrombus was
      considered stable and clinical observation was continued. In the THR group, 1/22
      and in the TKR group 9/58 were found to have distal DVT. All were asymptomatic.
      On follow-up scanning, none showed proximal propagation. All patients were
      followed up for at least 18 months, and none showed postthrombotic symptoms.
      Isolated distal DVT in "low-risk" Chinese patients after THR or TKR is not
      uncommon. Clinically they are usually "silent." If routine perioperative
      pharmacologic antithrombotic prophylaxis is not practiced, monitoring with duplex
      ultrasonography may need to be considered.

PMID- 12799761
TI  - An anatomic study of the popliteofibular ligament.
AB  - Our study was prompted by the varied reports in literature about the existence of
      the popliteofibular ligament as an integral part of the posterolateral corner of
      the knee. We performed 25 formalinised cadaveric knee dissections and identified
      the popliteofibular ligament. It was on an average 11.06 (5-16) mm in width and
      11.8 (6-16) mm in length. Our study did not include a functional evaluation. We
      found the ligament to be a constant structure of the posterolateral knee complex,
      and recommend its repair in acute injuries as well as reconstruction in chronic
      injuries of the posterolateral corner of the knee.

PMID- 12799762
TI  - Proximal femoral reconstruction with custom mega prosthesis.
AB  - Seventy-seven patients with proximal femoral tumours underwent limb salvage
      surgery with custom mega prostheses between July 1989 and January 2002. We
      describe 44 cases with a mean follow-up of 57.8 months. Forty-one patients
      presented with malignant neoplasms of which 11 were malignant giant cell tumours,
      eight were chondrosarcoma and five were metastases. Wide margins were achieved
      for all malignant tumours, and marginal resection was done for all benign and
      metastatic lesions. Six patients died of disease and two were lost to follow-up.
      Mechanical complications were observed in six cases, fracture being the most
      common. Oncological complications occurred in five patients. Functional activity
      was satisfactory in 79% of patients.

PMID- 12799763
TI  - Correlation between power Doppler ultrasonography and clinical severity in
      Achilles tendinopathy.
AB  - Twenty-five patients with chronic Achilles tendinopathy were clinically and
      ultrasonographically evaluated. A positive correlation existed between power
      Doppler ultrasonography (PDU) and tendon thickness (r=0.63, p<0.001) and
      patient's age (r=0.40, p<0.05). A negative correlation existed between PDU and a
      functional test (number of toe raises to pain) (r=-0.57, p<0.005) and one
      recorded item of the Victorian Institute of Sport Assessment Achilles score (VISA
      A questionnaire, item 6: jumping capability) (r=-0.46, p<0.05). Three patients
      had no detectable blood flow on PDU. PDU of Achilles tendons does not seem to be
      strictly related to symptoms but rather to functionality and chronicity of
      tendinopathy as indicated by toe-raises testing, jumping capability, patient age
      and tendon thickening.

PMID- 12799764
TI  - New technology for assessing microstructural components of tendons and ligaments.
AB  - This study investigated the ability of optical coherence tomography (OCT), a
      recently developed technology with micron-scale resolution, to assess the
      microstructure of tendons and ligaments. In vitro structural- and polarization
      sensitive OCT was performed on human ACL, Achilles tendon, and biceps tendon
      (obtained postmortem). Histology was performed on all imaged samples and compared
      to the corresponding OCT data. OCT images correlated well with histology. Most
      importantly, through polarization-sensitive OCT, the collagen in normal tissue
      was easily distinguished from the surrounding, supportive tissue due to the
      birefringent properties of organized collagen. Since the integrity of collagen is
      an important indicator of structural stability and pathologic state, the ability
      of OCT to assess collagen could be a powerful diagnostic tool in assessing tendon
      and ligament properties.

PMID- 12799765
TI  - Anterior displacement correlates with neurological impairment in cervical facet
      dislocations.
AB  - We studied all patients with either unifacetal or bifacetal dislocations treated
      in our National Spinal Injuries Unit between January 1996 and December 2000.
      There were 25 cases, of which 13 were unifacetal and 12 bifacetal. Craniocervical
      traction was employed in 21 cases and closed reduction achieved in 11. Eighteen
      patients underwent surgical stabilisation. Traction weights of up to 36 kg were
      employed, but there was no relationship found between the level of dislocation
      and traction weight. Anterior translation was measured by a newly described
      method, and we found a statistically significant correlation between the
      neurological score on admission and the degree of anterior translation.

PMID- 12799766
TI  - About neurophysiological evaluation in suprascapular nerve entrapment and methods
      of review.

PMID- 12799770
TI  - Difference in uptake and toxicity of trivalent and pentavalent inorganic arsenic
      in rat heart microvessel endothelial cells.
AB  - Intake of inorganic arsenic is known to cause vascular diseases as well as skin
      lesions and cancer in humans. We investigated the differences in cytotoxicity,
      uptake rate of arsenic, and gene expression of antioxidative enzymes between
      arsenite (As(3+))- and arsenate (As(5+))-exposed rat heart microvessel
      endothelial cells. As(3+) was more cytotoxic than As(5+), and LC(50) values were
      calculated to be 36 and 220 micro M, respectively. As(3+) (1-25 micro M)
      increased mRNA levels of antioxidant enzymes such as heme oxygenase-1 (HO-1),
      thioredoxin peroxidase 2, NADPH dehydrogenase, and glutathione S-transferase P
      subunit. HO-1 mRNA levels showed the most remarkable increase in response to
      As(3+). cDNA microarray analysis indicated that there was no prominent difference
      in arsenic-induced transcriptional changes between As(3+)- and As(5+)-exposed
      cells, when the cells were exposed to one-fourth the LC(50) concentration of
      arsenic (9 and 55 micro M for As(3+) and As(5+), respectively). N-acetyl- l
      cysteine (NAC) reduced both the cytotoxicity of inorganic arsenic and the HO-1
      mRNA level, and buthionine sulfoximine enhanced cytotoxicity of inorganic
      arsenic. As(3+) was taken up by the endothelial cells 6-7 times faster than
      As(5+), and the presence of NAC in the culture medium did not change the uptake
      rate of As(3+). These results suggest that the effects of NAC on arsenic-induced
      cytotoxicity and oxidative stress were due to the antioxidative role of non
      protein thiols and not to chelation of arsenic in the culture medium. The
      difference in cellular uptake of arsenic between As(3+) and As(5+) appeared not
      to be due to the ionic charge on arsenic (at physiological pH, trivalent arsenic
      is neutral whereas pentavalent arsenic is negatively charged). These results
      suggest that the higher toxicity of As(3+) compared with that of As(5+) is
      probably due to the faster uptake of As(3+) by endothelial cells, and inorganic
      arsenic exerts its toxicity at least in part via intracellular oxidative stress.

PMID- 12799771
TI  - Fractional contribution of lung, nasal and gastrointestinal absorption to the
      systemic level following nose-only aerosol exposure in rats: a case study of 3.7-
      micro m fluorescein aerosols.
AB  - Because absorption takes place from multiple sites of aerosol deposition, it is
      generally difficult to interpret systemic levels following nose-only inhalation
      in laboratory rodents. Therefore, this study attempted to determine the
      fractional contribution of lung, nasal and gastrointestinal (GI) absorption to
      the observed systemic level following nose-only aerosol exposure in rats using
      fluorescein as a model powder solute. Rats were treated orally with vehicle or
      activated charcoal, the latter diminishing GI absorption of fluorescein, and were
      subsequently nose-only exposed to 3.7- micro m fluorescein aerosols at 25.2 micro
      g/l(air) for 10 min. While fluorescein similarly disappeared from the lung at a
      half-life of 0.23 hr, its plasma concentrations in the charcoal-treated group
      were significantly lower than those in the charcoal-untreated (vehicle) group.
      This suggests that significant portions of fluorescein were transported by
      nasopharyngeal and tracheobronchial mucociliary clearances following aerosol
      exposure and were absorbed from the GI tract. Despite the lack of GI absorption
      in the charcoal-treated animals, it was estimated that this nose-only exposure of
      fluorescein allowed 25.7 and 82.5 micro g/kg of simultaneous lung and nasal
      deposition, respectively, followed by their absorption composing the observed
      systemic level in this group (AUC(0- infinity ) 137.49 ng/ml h). Thus, assuming
      linear pharmacokinetics of fluorescein, the extent of absorption (AUC(0- infinity
      )) due to such nasal deposit (82.5 micro g/kg) was estimated to be 47.00 ng/ml h
      using the AUC(0- infinity ) obtained in an independent study of intranasal powder
      insufflation at 34.5 micro g/kg in the charcoal-treated rats (AUC(0- infinity )
      19.66 ng/ml h). As a result, the AUC(0- infinity ) due to 25.7 micro g/kg of the
      lung deposit was deconvoluted to be 90.49 ng/ml h and finally, the absolute
      bioavailability (F%) of the "lung-region-specific" deposition and absorption of
      fluorescein was estimated to be 55.0%. It is observed therefore, that lung, nasal
      and GI absorption accounted for 24.2, 12.5 and 63.3% of the total fluorescein
      absorption, respectively, following nose-only exposure of 3.7- micro m aerosols.
      This study addresses the common methodological insufficiency of nose-only
      inhalation studies in rodents, which have been neglected in most cases, and
      provides the appropriate kinetic interpretation for their observed systemic
      level.

PMID- 12799772
TI  - Toxicokinetics of cyanide in rats, pigs and goats after oral dosing with
      potassium cyanide.
AB  - The aim of the present study was to determine the effect of the species on the
      toxicokinetics of cyanide and its main metabolite, thiocyanate. Forty-two rats,
      six pigs and six goats were dosed orally with 3.0 mg KCN/kg body weight, and
      cyanide and thiocyanate concentrations in blood were measured within 24 h. After
      the single oral dose, KCN was rapidly absorbed by rats and goats, with a time of
      peak concentration ( T(max)) of 15 min. The maximum plasma concentration (
      C(max)) of cyanide was observed in goats (93.5 micro mol/l), whereas the C(max)
      of thiocyanate was higher in rats (58.1 micro mol/l). The elimination half-life (
      t(1/2)) and volume of distribution ( Vd(area)) of both cyanide and thiocyanate
      were higher in goats (1.28 and 13.9 h, and 0.41 and 1.76 l/kg, respectively).
      Whereas the area under the curve (AUC) of cyanide was significantly higher in
      goats (234.6 micro mol.l/h), the AUC of thiocyanate was higher in rats (846.5
      micro mol.l/h). In conclusion, the results of the present study support the
      hypothesis that the metabolism of cyanide and its main metabolite, thiocyanate,
      is species-linked, with the goat being more sensitive to the toxic effects of
      cyanide/thiocyanate.

PMID- 12799773
TI  - A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic
      aromatic hydrocarbons in LNCaP human prostate carcinoma cells.
AB  - The role of aryl hydrocarbon receptor (AhR) on the antiandrogenic effects of
      polycyclic aromatic hydrocarbons (PAHs) was studied in LNCaP cells. The PAHs used
      in this study were chrysene (Chr), benzo[ k]fluoranthene (BkF), benzo[ a]pyrene
      (BaP), anthracene (Ant) and pyrene (Pyr). Chr, BkF and BaP acted as AhR agonists
      in LNCaP cells, while Ant and Pyr did not. The antiandrogenic effects of the PAHs
      were evaluated on the basis of regulation of prostate-specific antigen (PSA) mRNA
      and protein levels by 5alpha-dihydrotestosterone (DHT). Chr, BkF and BaP
      exhibited an antiandrogenic effect, but Ant and Pyr did not. alpha-Naphthoflavone
      (alpha-NF), an AhR antagonist, reversed the antiandrogen action of Chr, BkF and
      BaP, suggesting a requirement for activated AhR. The antiandrogenic PAHs did not
      significantly decrease androgen receptor (AR) levels or cellular DHT
      concentrations. Gel mobility shift assays revealed that Chr, BkF and BaP
      inhibited the binding of AR in nuclear extracts to oligonucleotide probes
      containing the AR-responsive element (ARE), whereas Ant and Pyr had no effect.
      The antiandrogenic PAHs elevated mRNA levels of c-fos and c-jun. Since activator
      protein-1 (AP-1), a heterodimer of c-jun and c-fos proteins, is known to inhibit
      binding of AR to ARE by protein-protein interaction with AR, the findings in the
      present study suggest a possible involvement of AP-1 in the antiandrogenic
      effects of PAHs acting as AhR agonists. These results suggest that AhR can
      stimulate AP-1 expression resulting in inhibition of the binding of AR to ARE in
      the transcription regulatory region of target genes such as PSA.

PMID- 12799774
TI  - Changes in the structure and function of the kidney of rats chronically exposed
      to cadmium. I. Biochemical and histopathological studies.
AB  - The aim of this study was to assess the effects of chronic exposure to cadmium
      (Cd) on the structure and function of kidneys, as well as to establish the body
      burden of Cd at which the changes occur. For this purpose we have created an
      experimental model using rats intoxicated with Cd administered in drinking water
      at the concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. The degree of
      kidney damage was evaluated biochemically and histopathologically. Sensitive
      biomarkers of Cd-induced proximal tubular injury such as urinary total N-acetyl
      beta- d-glucosaminidase (NAG-T) and its isoenzyme B (NAG-B), and alkaline
      phosphatase (ALP) were used. Cd content in the kidney increased with the level
      and duration of exposure leading to dose- and time-dependent structural and
      functional renal failure. In rats exposed to 5 mg Cd/l, first symptoms of injury
      of the main tubules of long and short nephrons (structural damage to epithelial
      cells, increased urinary activities of NAG-T and NAG-B) were noted after 12 weeks
      of the experiment. The damage occurred at a low kidney Cd concentration amounting
      to 4.08+/-0.33 micro g/g wet weight (mean +/-SE) and a urinary concentration of
      4.31+/-0.28 micro g/g creatinine. On exposure to 50 mg Cd/l, damage to the main
      tubules (blurred structure of tubular epithelium, atrophy of brush border,
      partial fragmentation of cells with release of nuclei into tubular lumen as well
      as increased urinary activities of NAG-T, NAG-B and ALP) was already evident
      after 6 weeks with the kidney Cd concentration of 24.09+/-1.72 micro g/g wet
      weight. In rats exposed to 50 mg Cd/l, a lack of regular contour of glomeruli was
      noted after 12 weeks, whereas after 24 weeks thickening of capillary vessels and
      widening of filtering space were evident. After 24 weeks of exposure to Cd,
      increased urea concentration in the serum with simultaneous decrease in its level
      in the urine, indicating decreased clearance of urea, and increased excretion of
      total protein were observed, but endogenous creatinine clearance remained
      unaffected. At the lower exposure, symptoms of structural, but not functional,
      damage to the glomeruli were also evident after 24 weeks of the experiment. Our
      results provide evidence that chronic exposure to Cd dose-dependently damages
      (structurally and functionally) the whole kidney. The injury affects the main
      resorptive part (proximal convoluted tubules and straight tubules) and the
      filtering part (glomeruli) of the nephron. But the target site for Cd action is
      the main tubule. We hypothesize that the threshold for Cd effects on the kidney
      is less than 4.08+/-0.33 micro g/g wet kidney weight and greater than 2.40+/-0.15
      micro g/g (at this Cd concentration no symptoms of kidney damage were noted), and
      it may be close to the latter value. A very important finding of this study is
      that Cd acts on the whole kidney, especially on the main tubules, even at
      relatively low accumulation in this organ. It confirms the hypothesis that humans
      environmentally exposed to Cd, especially smokers, are at risk of tubular
      dysfunction.

PMID- 12799775
TI  - Consecutive administration of paraquat to rats induces enhanced cholesterol
      peroxidation and lung injury.
AB  - It is our hypothesis that as a consequence of increased oxidative stress, rats
      develop lung injury with increased cholesterol-derived hydroperoxides and
      oxysterols in lung after consecutive exposure of the rats to paraquat. To test
      this we administered 10 mg/kg of paraquat i.p. once or seven times (once a day)
      to Wistar rats. Rats were killed, and lung tissue was collected 24 h after the
      last paraquat injection. We found that in response to consecutive paraquat doses,
      there were significant increases in 7alpha- and 7beta-hydroperoxycholest-5-en
      3beta-ol (7alpha-OOH and 7beta-OOH; P=0.01) as well as 7alpha- and 7beta
      hydroxycholesterol (7alpha-OH and 7beta-OH; P=0.01), and 7-ketocholesterol (7
      keto; P=0.03). In addition, pulmonary hemorrhage, thickening of alveolar septum,
      and inflammatory cell infiltration of macrophages were observed. This is the
      first report showing enhanced cholesterol peroxidation and lung injury of rats
      due to consecutive doses of paraquat.

PMID- 12799776
TI  - Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro.
AB  - 2,3,7,8-Tetrachloro-dibenzo- p-dioxin (TCDD) is a ubiquitously distributed
      xenobiotic. The adverse effects of TCDD on the mammalian immune system have been
      studied for decades, but it is still unclear whether TCDD has direct effects on T
      lymphocytes or whether it acts via the thymic microenvironment. We have studied
      the effects of TCDD on primary cultures of human thymic epithelial cells (TEC)
      focusing on differentiation markers, integrins and adhesion molecules involved in
      cell-cell and in cell-matrix interactions. TEC were treated with TCDD at
      concentrations of 0.001, 0.01, 0.1, 1.0 or 10.0 nM or with 100 nM PCB 126
      (3,3',4,4',5-pentachlorobiphenyl) for 3 days, and were then analysed by flow
      cytometry for expression of surface antigens using monoclonal antibodies against
      Hassall's bodies (TE-8, TE-16) or against surface structures such as CD29, CD49b,
      CD49e, CD49f, CD51, CD54, CD58, CD61 and CD106. At TCDD concentrations as low as
      0.01 nM we found a significant increase in terminally differentiated, TE-16
      positive TEC; at a ten-fold greater concentration the number of cells marked with
      the TE-8 antibody was also increased. With both markers the most pronounced
      effect (approximately +15%) was observed at 1 nM TCDD. An increase of cells
      expressing the integrin alpha-chains CD49b, CD49e and CD51 as well as CD54 was
      observed at concentrations of 0.1 nM TCDD or higher. The proportion of cells
      expressing CD106 or CD49f decreased significantly upon treatment with TCDD. No
      effects on the integrin beta-chains CD29 and CD61 could be detected. Overall, PCB
      126 induced similar changes to TCDD. In summary, TCDD and a coplanar PCB induced
      terminal differentiation of human TEC along with changes of integrins and other
      adhesion molecules. These receptors and their interplay with the extracellular
      matrix have key functions in the maturation of T-lymphocytes and it is plausible
      that their alteration would be involved in TCDD-induced immunotoxicity.

PMID- 12799777
TI  - Urban-rural differences in the occurrence of female depressive disorder in Europe
      -evidence from the ODIN study.
AB  - BACKGROUND: In an earlier paper of the European multi-centre ODIN study (Ayuso
      Mateos et al. 2001) we found remarkable urban preponderance in comparison to the
      corresponding rural site in the female prevalence of depressive disorder in the
      UK and Ireland. The aim of this paper is to analyse the possible reasons for this
      finding. METHOD: A representative sample of 12,702 people aged between 18 and 64
      residing in specified urban and rural areas were screened by the Beck Depression
      Inventory (BDI) for depressive disorder in four European countries (Finland,
      Ireland, Norway and the UK). Those over cut-off (BDI score < 12) and a 5 % random
      sample of those under cut-off underwent diagnostic interview including the SCAN
      version 2.0, and completed a battery of additional research instruments. RESULTS:
      The estimated 1-month prevalence of depressive disorder according to ICD-10 was 9
      % in the total ODIN sample. A large between-country variation was found in female
      urban prevalence, with Ireland (Dublin) and the UK (Liverpool) having a
      remarkably high rate. The women in these same countries showed a significant
      urban/rural difference, whereas in men and in the total sample this difference
      was non-significant. Logistic regression analysis including some selected risk
      factors of depression showed still higher risk of depressive disorder both in
      Dublin and Liverpool compared with the Finnish urban site (Turku), which had the
      lowest urban prevalence. In addition, also such factors as lack of confidant and
      having difficulties in getting practical help from neighbours were important
      predictors of depressive disorder. Similarly, when analysing the different
      countries separately, the significance of the urban/rural difference in women
      remained for Ireland and the UK, indicating that the other risk factors studied
      could not totally explain the difference. CONCLUSIONS: ODIN is the first European
      study on occurrence of depressive disorder in both urban and rural settings
      allowing closer analysis of the urban/rural differences. The most striking result
      was the large urban/rural difference in women in the two countries from the
      British Isles which could not be totally explained by the socio-demographic
      factors included in this study.

PMID- 12799778
TI  - Recall bias and major depression lifetime prevalence.
AB  - BACKGROUND: Epidemiological studies have reported lifetime prevalence rates for
      major depression that have typically ranged between 10 % and 20 %, and have
      typically been fairly stable across age groups. This contradicts the intuitive
      expectation that lifetime prevalence should accumulate with age. Some authors
      have hypothesized that a cohort effect may account for this puzzling pattern, but
      another possible explanation is recall bias. In principle, differential mortality
      could also account for a failure of age-specific lifetime prevalence to increase
      with age. The objective of this study was to describe the relationship between
      recall failure (failure to recall previous depressive episodes) and bias in the
      evaluation of age-specific lifetime major depression prevalence. METHOD: A
      framework recently described by Hill et al. was used in this analysis. Hill's
      model relates the slope of an age-specific prevalence curve for an irreversible
      disease to incidence and mortality. The model is applicable in the current
      context since lifetime major depression is, by definition, an irreversible
      condition (albeit one typically characterized by recurring episodes). In the
      current investigation, an extra term for recall failure was added to the model.
      In order to incorporate mortality, a structured literature review was conducted
      and the impact of plausible levels of differential mortality was explored.
      RESULTS: Relatively low rates of recall failure (e. g. 2-4 % per year) can
      account for a flat or declining age-specific lifetime prevalence curve in most
      age groups, with higher rates of recall failure being necessary in the adolescent
      age range. Among the elderly, where mortality rates are higher, differential
      mortality may also contribute to the pattern. CONCLUSIONS: Available data about
      the incidence of major depression, and the mortality associated with this
      condition, suggest that plausible rates of recall failure can explain a flat or
      declining lifetime major depression prevalence across age groups. A corollary of
      this result is that many existing estimates of major depression lifetime
      prevalence may be too low. A cohort effect can be inferred from cross-sectional
      lifetime prevalence data only when the diagnostic instruments employed make
      recall failure very unlikely.

PMID- 12799779
TI  - Excess mortality among long-stay psychiatric patients in Northern Finland.
AB  - BACKGROUND: According to several studies, mortality in psychiatric patients is
      higher than in the general population, but cause-specific mortality analyses in
      long-stay psychiatric patients have not been studied very much. Individual follow
      ups have been called for in order to identify possible treatment deficiencies and
      to make recommendations for clinical practices. In this study, mortality of long
      stay psychiatric patients has been monitored for the years 1992-2000 and
      contrasted with that prevalent in the general population. METHOD: Data on
      psychiatric patients (N = 253) who were treated without a break for at least 6
      months during 1992 in the Department of Psychiatry at Oulu University Hospital
      were linked with the National Death Register. Standardised mortality rates (SMRs)
      were determined according to gender, age groups, and different causes of death.
      RESULTS: Of the total study population, 80.2 % had schizophrenia, 5.1 % other
      functional psychoses, 9.5 % organic mental disorders, 2.4 % personality disorders
      and 2.8 % mood disorders. Sixty-nine (27.3 %) of the patients (aged 31-88 years)
      had died before the end of the year 2000. The all-cause death risk for both males
      and females was four times that of the general population. The mortality risk was
      over ten-fold for males and almost 30-fold for females in the youngest age group
      (25-34 years), with suicides explaining about 75 % of these deaths. SMRs were
      found to decrease at older age, mortality thus approaching that of the general
      population. Diseases of the circulatory system were the most common single cause
      of death in both genders and mortality due to that cause exceeding mortality in
      the general population nearly 3.6-fold. However, the probability of death was
      highest (SMR 17.5) in connection with diseases of the digestive system. Increased
      risks of death due to respiratory complications (SMR 9.3), accidents (SMR 5.1)
      and neoplasms (SMR 2.1) were also noted. The overall death rates did not differ
      in relation to social class or professional education. CONCLUSIONS: Long-stay
      psychiatric patients were found to die from the same natural causes as the rest
      of the general population. However, the mortality risk of the long-stay
      psychiatric patients compared with that of the general population was notably
      higher, despite ongoing improvements in medical care and facilities. Inadequately
      organised somatic care and the prevailing culture of "non-somatic" treatment in
      psychiatry were suggested to, at least in part, explain this phenomenon.
      Attention ought to increasingly focus on somatic examinations and various health
      educational programmes specially designed for psychiatric patients and involving
      matters like healthy diet, smoking cessation and physical exercise. These
      practices should be a regular part of any patient's treatment programme. Also,
      the need to recognise factors associated with a patient's psychiatric disorder
      that could limit that patient's ability to communicate somatic symptoms and/or
      even lead to a refusal by that patient to have somatic diseases treated was seen
      as essential for providers of psychiatric services.

PMID- 12799780
TI  - Reasons for the diagnostic discordance between clinicians and researchers in
      schizophrenia in the Northern Finland 1966 Birth Cohort.
AB  - BACKGROUND: The diagnosis of schizophrenia by clinicians is not always accurate
      in terms of operational diagnostic criteria despite the fact that these diagnoses
      form the basis of case registers and routine statistics. This poses a challenge
      to psychiatric research. We studied the reasons for diagnostic discordance
      between clinicians and researchers. METHODS: The Northern Finland 1966 Birth
      Cohort (n = 11,017) was followed from mid-gestation to the end of the 31st year.
      Psychiatric outcome was ascertained through linkage to the national hospital
      discharge register containing clinical diagnoses made by the attending physician.
      The hospital notes of all subjects admitted to hospital during the period 1982
      1997 due to psychiatric disorder were reviewed and 475 research, operational DSM
      III-R diagnoses were formulated. RESULTS: Ninety-six cases met operational
      criteria for schizophrenia. Fifty-five (57 %) had concordant diagnoses: both the
      clinical and research diagnoses were schizophrenia. Forty-one (43 %) had
      discordant diagnoses: the clinical diagnosis was other than schizophrenia (mainly
      schizophreniform or other psychosis). Discordant cases were more likely to be
      older at onset, experience a shorter treatment duration, fewer treatment
      episodes, and to have a comorbid diagnosis mental retardation. CONCLUSIONS:
      Clinicians do not make the diagnosis of schizophrenia as often as the application
      of operational criteria would suggest they should. The discordance between
      clinical diagnosis and the research, operational diagnosis is especially likely
      in cases having late onset and few contacts to psychiatric hospital.

PMID- 12799781
TI  - Health beliefs link to duration of untreated psychosis and attitudes to later
      treatment in early psychosis.
AB  - BACKGROUND: Health beliefs influence health behaviours and have been shown to
      influence outcomes in a variety of illnesses, treatments and preventative
      interventions. AIMS: We aimed to measure health beliefs in first episode
      psychosis with the hypotheses that their structure would resemble that in
      physical illness (diabetes) and would correlate with prior duration of untreated
      psychosis and later attitudes to treatment. METHOD: The Multidimensional Health
      Locus of Control scale was used in a sample of 50 people with schizophrenia
      during the first episode and at 18-month follow-up, 51 diabetic controls and 51
      normal controls. RESULTS: Schizophrenia patients, both at first episode and 18
      months later, had a pattern of health beliefs that was similar to those of the
      patients with diabetes and significantly different to the normal controls. There
      were significant associations between internal locus of control score and short
      DUP, and between external locus of control score and a positive attitude to
      medication as measured by the Drug Attitudes Inventory. CONCLUSIONS: Health
      beliefs in first episode schizophrenia correlate with determinants of outcome.

PMID- 12799782
TI  - Psycho-social determinants for psychiatric hospitalisation for neurotic disorders
      in women--a case-control study.
AB  - BACKGROUND: Much has been written about the determinants of psychiatric
      hospitalisation, chiefly for psychotic patients in an emergency. This paper
      reports the results of a comparative study between in-patients and pathological
      subjects from the general population. The aim of this work is to evidence the
      psycho-social determinants of hospitalisation in a psychiatric department for
      neurotic disorders. METHODS: This study was conducted on a socially fairly
      privileged population which was, therefore, also fairly homogeneous. The subjects
      from the two groups were assessed clinically using standardised instruments both
      for diagnosis (SCAN) and for psycho-social variables (Stressful Life Events:
      LEDS; Social Support and Self-esteem: Pearlin checklist; care itinerary).
      RESULTS: Following the analysis of frequency and a multivariate logistic
      regression analysis, four risk factors for hospitalisation for neurotic disorders
      were evidenced, including: severity of neurotic disorders, taking a long time to
      consult a specialist after first onset of anxiety disorders, poor social support,
      and having experienced one or more provoking agents (Brown and Harris
      methodology) in the year previous to hospitalisation. CONCLUSION: The severity of
      the mental pathology is largely responsible for hospitalisation in neurotic
      patients as it is in psychotic patients, but it is not the only determinant for
      hospitalisation.

PMID- 12799783
TI  - Victim relations and victim gender in violent crimes committed by offenders with
      schizophrenia.
AB  - BACKGROUND: Family members and friends appear to be most at risk of becoming
      victims of violence committed by offenders with major mental disorders. The aim
      of the present study is to examine, in a national sample, victim relation in
      violent crimes committed by male offenders with schizophrenia, with special
      reference to victim gender and the severity of violence. METHOD: We identified
      all violent offenders who were diagnosed with schizophrenia in forensic
      psychiatric evaluations during the years 1992-2000 and examined their court
      convictions. In total 588 victims were included, 327 men and 261 women, and
      distributed into three groups based on their relation to the offender: Family of
      origin (n = 77), Network (n = 183) and Unacquainted (n = 328). RESULTS: The
      majority of the victims were unacquainted with the offender, but the violence was
      less severe in this group. Among family members, e. g. parents, siblings and
      grandparents, there were more female than male victims (60 % vs 40 %), and
      victims in families, as well as males within the offender's network, were those
      most likely to be seriously or fatally injured. Female family victims, in
      particular mothers, were those most likely to die as victims of severe violence.
      CONCLUSIONS: The study highlights the risk for family members and the immediate
      network of becoming a target of violence. Mental health services together with
      community-based services have an important task in identifying risk situations
      and taking preventive measures.

PMID- 12799784
TI  - Attitudes toward obsessive-compulsive disorders--an experimental investigation.
AB  - BACKGROUND: Fear, embarrassment and stigma are salient factors contributing to
      reluctance to seek help for psychological distress. Although vignette studies
      have often been employed to assess attitudes towards psychological disorders, no
      study has specifically assessed attitudes towards Obsessive-Compulsive Disorder
      (OCD). METHODS: An experimental study assessing attitudes toward obsessive
      compulsive problems is presented. One hundred and thirteen undergraduate students
      were given vignettes describing three subtypes of obsessive-compulsive problem
      (harming, washing and checking). They were asked to make judgements about fear,
      shame and social acceptance, and to evaluate how they themselves might feel if
      they experienced the problems described in the vignettes. RESULTS: The obsessive
      compulsive problems described in the vignettes were evaluated differently in
      terms of shame, fear and social acceptance. The harming problems were rated as
      being the most unacceptable, followed by the washing behaviour, and then the
      checking behaviour. CONCLUSION: The findings suggest that attitudes to obsessive
      compulsive problems are likely to be complex and that help-seeking influences may
      vary across the different subtypes of this disorder. The implications for people
      seeking help for obsessive-compulsive problems are pointed out.

PMID- 12799785
TI  - Reducing psychiatric stigma and discrimination--evaluating an educational
      intervention with the police force in England.
AB  - BACKGROUND: Across the world there are programmes challenging negative
      stereotypes of people with mental health problems and associated discriminatory
      behaviours, but the evidence base describing what works in practice is still
      underdeveloped. This paper evaluates the effectiveness of a mental health
      training intervention with the police force in England. METHOD: A total of 109
      police officers attended training workshops and completed pre- and post
      questionnaires detailing knowledge, attitudes and behavioural interventions.
      RESULTS: Mean attitude scores fell from 2.4 at baseline to 2.3 at follow-up (p <
      0.0001) using a 5-point Likert scale. Five key message statements were assessed -
      70 % of cases successfully reported more messages at follow-up as compared to
      baseline; however, the stereotype linking people with mental health problems with
      violent behaviour overall was not successfully challenged. Positive impacts on
      police work, particularly improvements in communication between officers and
      subjects, were reported by a third of cases. CONCLUSIONS: Short educational
      interventions can produce changes in participants' reported attitudes towards
      people with mental health problems, and can leave police officers feeling more
      informed and more confident to support people in mental distress.

PMID- 12799786
TI  - [Evaluation of stent-protected angioplasty for theray of symptomatic stenoses of
      the carotid artery. SPACE and other randomized trials].
AB  - During recent years, stent-protected angioplasty of the carotid artery (SPAC) has
      become an alternative to endartectomy (CEA) in many centers. Despite many case
      reports, case series, and open records, it has not been proven that these
      therapeutical regimens are comparable regarding complication rates and long-term
      outcome. Until now, only three randomized trials were published on this theme,
      two of them only as abstracts. This is not sufficient for answering the question
      of whether SPAC is a good alternative to CEA. At present, four major, randomized,
      multicenter trials are being run (EVA3S in France, CREST in the US, ICSS in Great
      Britain and several other countries, and SPACE in Germany and Austria). About
      7,300 patients will be included in these trials. At present, 24 centers are
      participating in the SPACE trial, recruiting about 350 patients. It has been
      prospectively agreed that EVA-3S, ICSS, and SPACE will combine their results
      after completion of initial randomization and follow-up to conduct a combined
      European meta-analysis of the data. Three to 5 years are needed until these
      trials' final results will be published. Until then, stent-protected angioplasty
      should be done only under the consideration that it has not been scientifically
      evaluated.

PMID- 12799787
TI  - [Fabry's disease: new therapeutic options for this lysosomal storage disorder].
AB  - Fabry's disease is an x-linked, recessive, lysosomal storage disorder that
      results from deficient alpha-galactosidase A activity with pathological
      sphingolipid deposition mainly in endothelium, smooth muscle cells, kidneys,
      central and peripheral nervous system, and myocardium. Clinical manifestation
      mostly occurs during childhood and adolescence with severe pain attacks or
      chronic pain mainly in hands and feet, hypohydrosis, and skin lesions
      (angiokeratoma). In more advanced disease stages, renal and cerebrovascular
      complications develop with proteinuria and later renal failure and cerebral
      ischemia caused by cerebral microangiopathy, dilatative arteriopathy, or cardiac
      embolism. Heterozygote female carriers are severely affected more often than was
      previously considered. The diagnosis is based on the detection of deficient alpha
      galactosidase A activity in leukocytes, fibroblasts, or tissue biopsies. Two
      randomised placebo-controlled studies showed that enzyme replacement is effective
      by demonstrating either reduced pain or reduced tissue sphingolipid deposition.
      Early diagnosis of Fabry's disease is important in view of these new causal
      therapeutic options.

PMID- 12799788
TI  - [Hereditary spastic paraplegias].
AB  - Hereditary spastic paraplegias (HSP) are characterised by symmetric spastic
      paraplegia, pallhypaesthesia, and urinary dysfunction (uncomplicated HSP).
      Complicated HSP is present if uncomplicated HSP additionally presents with
      epilepsy, dementia, cataract, extrapyramidal dysfunction, amyotrophy,
      polyneuropathy, or ichthyosis. Clinically, HSP are similar but genetically even
      more heterogeneous. The disease course is slowly progressive and, the earlier the
      disease onset, the slower the course. Causes of HSP are mutations in 20 different
      genes, of which eight have been identified so far. A single mutation can cause
      complicated and uncomplicated HSP. Onset and severity can be quite variable
      between both groups and within families. Despite molecular genetic advances,
      diagnosis of HSP still relies on clinical features and the exclusion of various
      differential diagnoses. Neuropathologically, there is degeneration of
      corticospinal, posterior column, and spinocerebellar axons. Most likely,
      degeneration of the longest CNS axons is due to an impaired energy supply of the
      anterograde and retrograde axonal transport.

PMID- 12799790
TI  - [Muscle afferent block in the treatment of oromandibular dystonia. Difference in
      effect between masticatory and lingual muscles].
AB  - Oromandibular dystonia is a neuromuscular disorder characterized by tonic or
      clonic involuntary spasms of the masticatory and lingual muscles. We treated 50
      patients with this movement disorder by injection of lidocaine and alcohol into
      the masticatory or tongue muscles to block muscle afferents from muscle spindle.
      The patients were divided according to clinical features into four groups: jaw
      closing, jaw-opening, jaw-deviation, and tongue dystonias. Objective evaluation
      of the symptoms before and after therapy was based on a clinical scaling protocol
      in terms of four parameters (mastication, speech, pain, and discomfort scales).
      Symptoms improved in all patients without major side effects. The overall
      objective improvement (60.2+/-29.5%) was significantly (P<0.005, ANOVA) lower in
      tongue dystonia (14.1%) than in jaw-closing dystonia (67.6%) and jaw-opening
      dystonia (68.3%). Although the response of the muscle afferent block to tongue
      dystonia was hardly satisfactory, this treatment is suggested to be effective for
      oromandibular dystonia.

PMID- 12799789
TI  - [Rhabdomyolysis and myoglobinuria].
AB  - Rhabdomyolysis is a disorder characterized by acute damage of the sarcolemma of
      the skeletal muscle leading to release of potentially toxic muscle cell
      components into the circulation, most notably creatine phosphokinase (CK) and
      myoglobin, and is frequently accompanied by myoglobinuria. Therefore, the term
      myoglobinuria is often used interchangeably with the term rhabdomyolysis. This
      disorder may result in potential life-threatening complications such as acute
      myoglobinuric renal failure, hyperkalemia and cardiac arrest, disseminated
      intravascular coagulation, and compartment syndrome. The condition is
      etiologically heterogeneous and may result from a large variety of diseases
      affecting muscle membranes, membrane ion channels, and muscle energy supply
      including acquired causes (e.g., exertion, crush injury and trauma, alcoholism,
      drugs, and toxins) and hereditary causes (e.g., disorders of carbohydrate
      metabolism, disorders of lipid metabolism, or diseases of the muscle associated
      with malignant hyperthermia). In many patients with idiopathic recurrent
      rhabdomyolysis, specific inherited metabolic defects have not been recognized up
      to now.

PMID- 12799791
TI  - [Oral anticoagulation in symptomatic intracranial stenoses].
AB  - Symptomatic intracranial stenoses display an increased risk for ischemic stroke.
      Until now, only retrospective studies have demonstrated a positive effect of oral
      anticoagulation for prevention of further ischemic strokes. However, this therapy
      is widely used. The aim of the present study was to examine the efficacy and
      safety of oral anticoagulation for patients with symptomatic intracranial
      stenoses in clinical practice. Sixty-one patients with the diagnosis of
      symptomatic intracranial stenosis between 1992 and 1998 and who received oral
      anticoagulation were interviewed and examined in 2000. Ten patients suffered
      ischemic strokes (eight TIA, two completed strokes), and a subdural hematoma
      occurred in one patient. Six patients died during the observation period. In none
      of these cases was the death related to oral anticoagulation. Eight extracerebral
      bleedings occurred. An annual rate of 3% per year for ischemic strokes could be
      calculated. The annual rates for intracerebral and extracerebral bleeding
      amounted to less than 1% per year and 2.6% per year, respectively. Thus, oral
      anticoagulation in patients with symptomatic intracranial stenoses seems to be
      safe. Although the results suggest its efficacy, this cannot be proven due to the
      small number of patients examined and due to the design of the study.

PMID- 12799792
TI  - [Possibilities and limits of immunotherapy in multiple sclerosis. Inflammatory
      and degenerative aspects of the disease require a new pathogenetic concept].

PMID- 12799794
TI  - [Prevention of postherpetic neuralgia: does it exist?].
AB  - THEORETICAL CONSIDERATIONS: Several pathophysiological mechanisms may be
      responsible for initiation and maintenance of chronic postherpetic pain. (1)
      Peripheral nociceptive fibers can develop abnormal sensitization. Secondary to
      this, central nociceptive "second-order" neurons in the spinal cord dorsal horn
      can also be sensitized, i.e. they become hyperexcitable and start responding to
      non-noxious stimuli. (2) Degeneration of nociceptive neurons may trigger
      anatomical sprouting of low-threshold mechanosensitive terminals to form
      connections with central nociceptive neurons and may subsequently induce
      functional synaptic reorganization in the dorsal horn. According to these
      mechanisms theoretical possibilities of therapeutical interventions to prevent
      postherpetic neuralgia are (1) adequate analgesia in the acute phase (analgesics,
      antidepressants, sympathetic blocks) and (2) prevention of C-fiber degeneration
      by reducing the inflammatory reaction (antiviral drugs, corticosteroids,
      neurotrophins). CLINICAL EXPERIENCE: The present clinical trials concerning
      prevention of postherpetic neuralgia were analyzed. Only for the antiviral drugs
      have valid clinical studies been performed. Using acyclovir a considerable
      reduction of acute pain and time to healing could clearly be demonstrated.
      However, there was no significant effect on prevention of postherpetic neuralgia.
      The second-generation antiviral drugs valaciclovir and famciclovir may be more
      effective when applied early in the disease course. Preliminary studies indicate
      that the early onset of therapy with the antidepressant agent amitriptyline may
      reduce the incidence of postherpetic neuralgia. These results need to be
      confirmed in further studies. CONCLUSION: Although there is no clear evidence in
      favor of a prevention of postherpetic neuralgia for any of the interventions, it
      is definitely reasonable to perform the best analgesia possible during the acute
      phase of herpes zoster.

PMID- 12799795
TI  - [Quality control in the therapy of chronic pain. Results obtained by a task force
      of the German Section of the International Association for the Study of Pain on
      psychological assessment of chronic pain. XI. Assessment and multiaxial
      classification of pain].
AB  - This paper reviews instruments in German language for the psychological
      assessment and classification of pain. Usually chronic pain syndromes are
      classified within the International Classification of Diseases (ICD). Instead of
      the psychiatric chapter of the ICD, it is possible to use the Diagnostic and
      Statistical Manual of Mental Disorders (DSM). The proposed classification system
      of the International Association of the Study of Pain (IASP) is based on a
      multiaxial solution. The numerous ways to classify chronic pain include many
      problems and limits, especially in the case of an interdisciplinary assessment.
      They provide no specific system for classifying pain syndromes. They are
      impractical to handle and restrict classifying pain as either somatogenic or
      psychogenic. It is not possible to describe both sides in one diagnosis without
      loss of information. As a result of this situation, a task force of the German
      Chapter of the International Association for the Study of Pain developed a
      Multiaxial Classification of Pain (Multiaxiale Schmerzklassifikation; MASK) as an
      advanced system of pain assessment and an alternative to the common
      classification systems. MASK embraces a somatic (MASK-S) and a psychological
      (MASK-P) part. Both parts constitute an 'interdisciplinary diagnosis'. MASK-S
      enables classifying a pain syndrome using hierarchical levels, with progredient
      specific degrees of differentiation. In addition there are 6 axes to describe
      pain syndromes qualitatively and quantitatively (e.g. localization, quality). The
      psychosocial part (MASK-P) embraces 5 main levels (1. behavioral, 2. emotional,
      3. cognitive, 4. stress-related, 5. habitual personal factors) and 2 additional
      levels (6. functional coherence, 7. ICD/DSM-diagnosis additional). The MASK-P
      part of the diagnosis is composed of graduation on these levels. Differential
      axis of the pain syndromes are described phenomenologically and specifically.
      MASK provides the possibility of establishing an integrative, interdisciplinary
      diagnosis.

PMID- 12799796
TI  - [Fear-avoidance-beliefs in patients with backpain].
AB  - INTRODUCTION: In recent years most industrialized nations have been confronted
      with a dramatic increase in cases dealing with back pain which, because of the
      associated costs, has put a strain on health care systems. Because of the
      tremendous costs caused by patients with chronic illnesses, there is a common
      interest in identifying determinants responsible for the pain becoming chronic.
      According to the fear-avoidance model, chronic back pain is the cause of specific
      patient beliefs according to their perception and appraisal of back pain and
      their assumptions about the connection between pain and work activities. These
      fear-avoidance beliefs are assumed as the main cognitive factors of adapting to
      chronic invalidism. In this study a German version of a self-reporting instrument
      that assesses fear-avoidance beliefs (FABQ, Waddell et al. 1993) is presented.
      METHODS: A translated version of the "Fear-Avoidance Beliefs Questionnaire" was
      given to 87 patients with back pain, who took part in a multimodal treatment
      program in an outpatient pain unit. The questionnaire was administered at
      different times in the therapeutic process. We examined the factor structure of
      the questionnaire and conducted the first examinations concerning its
      psychometric properties. RESULTS: The results of our data set concerning
      different aspects of reliability and validity conform the good psychometric
      properties of the questionnaire. The factor analysis revealed a three-factor
      solution, which accounted for nearly 60% of the variance. The first factor made
      up 34% of the variance. The six corresponding items dealt with "back pain caused
      by work". The second factor made up 13% of the variance. The content of the 5
      items is focused on the patients' view about his/her probable return to work.
      Beliefs about physical activity in back pain (factor 3, 5 items) accounted for
      12% of the variance. Correlation analysis demonstrated that all three factors are
      of independent value, which showed satisfactory reliability. Furthermore, we
      analyzed the prognostic value of the three factor dimensions. Patients completed
      multidisciplinary treatment according to the concept of "functional restoration".
      At the end of treatment, factor 1 (causation by work) was not diminished, but
      both other factors showed significant reductions. In a discriminant factor
      analysis, back-to-work could be significantly predicted by factor 3 (beliefs
      about physical activity) and factor 2 (patients' prognosis about their probable
      return to work at the beginning of treatment). Furthermore, length of time off
      work and age accounted for an additive classification rate of 77%. The FABfactor
      1 (causation by work) was of no predictive value. CONCLUSIONS: The results
      suggest that primary target points for further investigation include an analysis
      of the patients' beliefs about their pain, with special emphasis on fear
      avoidance beliefs. It is also necessary to analyze the behavioral assumptions of
      the fear-avoidance model in an experimental design. Furthermore, our results
      concerning the psychometric properties of the questionnaire should be proved in a
      far larger sample of back pain patients.

PMID- 12799797
TI  - [Pain intensity and power densities of therapeutic ultrasound--a serial,
      comparative pilot study in patients with low back pain].
AB  - INTRODUCTION: A pilot study was conducted to provide an indication of the power
      density (PD) dependent analgesic effect of ultrasound (US) under serial
      application in patients with low back pain. METHODS: Thirty patients (n=3 x 10)
      were randomly assigned to one of three PDs (0.3, 0.7 or 1.0 W/cm(2)). Twelve
      treatments were applied once a day for 2 weeks. The sonation time per treatment
      was 10 minutes. Patients were unaware of their grouping. Pain intensity (PI) was
      assessed using a visual analogue scale for each treatment. The relationship
      between the different PI profiles was tested by repeated measures by ANOVA.
      RESULTS: The averaged duration of pain was over 10 years (chronic low back pain).
      Twenty-seven (n=3 x 9) patients could be analyzed (three drop-outs). In the
      medium (0.7 W/cm(2)) and high (1.0 W/cm(2)) PD groups the PI showed a clearly
      decreasing trend, while in the low (0.3 W/cm(2)) PD group, the PI remained
      stationary. None of the contrasts showed a locally significant effect (Bonferroni
      adjustment). CONCLUSIONS: The observed effect is presumably overestimated. In the
      low PD group, there were more people out of work, and fewer took analgesic drugs.
      No conclusive judgement is possible. The concept of the PD-dependent effect of US
      must be evaluated in trials with greater sample sizes.

PMID- 12799798
TI  - [Strong opioids for treatment of chronic pain: a meta-analysis].
AB  - In the following presentation 59 German and English articles on the use of strong
      opioids in chronic pain syndromes are analysed. Studies concerning the epidural,
      intrathecal, intracerebroventricular and transdermal application of opioids were
      excluded. The articles were attributed to different study levels according to
      their contents. The majority of articles (n=39, 66.1%) consisted of case
      presentations, while only 33.9% of the articles presented randomised (n=15) or
      non-randomised (n=5) study designs. The analgesic effect of the strong opioids
      morphine, buprenorphine and methadone in oral, rectal, subcutaneous and
      intravenous forms of application was confirmed for cancer-associated and non
      cancer-associated chronic pain. Altogether there is a lack of controlled clinical
      studies.

PMID- 12799799
TI  - [Anticonvulsive drugs in therapy of chronic pain--metaanalysis].
AB  - Anticonvulsive drugs provide good analgesic effect in the treatment of chronic
      neuropathic pain syndromes as well as in certain types of headache. Moreover
      these drugs may also be considered helpful for cases of non-neuropathic pain,
      especially if non-opioid analgesics are not effective. The optimal anticonvulsive
      drug for neuropathic pain is carbamazepine, while for headache prophylaxis
      valproic acid is recommended.

PMID- 12799800
TI  - [Psychological therapy modalities in chronic back pain].

PMID- 12799801
TI  - [Pain and disability as personal constructs].
AB  - This article reviews the empirical research which has examined the relationships
      among chronic pain and cognitions like attributions, coping, beliefs,
      expectations and problem solving. Methods for the examination of pain cognitions
      and coping strategies are reviewed. Current research which shows the significance
      of cognitions and coping for the chronification of pain states is reported. These
      findings are critically discussed. Other methods for future research are
      presented.

PMID- 12799802
TI  - [Indication and limits to behavioral therapy for patients with chronic pain].
AB  - Chronic pain has a variety of causes. Therefore patients with chronic pain should
      be treated in an interdisciplinary way. From a psychological point of view a
      cognitive-behavioral approach is preferred. This includes training for coping
      with pain as well as the added option of a comprehensive psychotherapy. This form
      of treatment seems to be indicated in most cases, but it is not suitable if the
      patient does not agree with the procedure, preferring instead a special kind of
      therapy which is not cognitive-behavioral. On the other hand a psychological
      treatment is not indicated if the therapist is not prepared to cooperate with
      other therapists in an interdisciplinary fashion.

PMID- 12799803
TI  - [Activation of trigeminal brain stem neurons by chemical stimulation of the dura
      mater encephali--preparation for studying meningeal nociception in the rat].
AB  - INTRODUCTION: Headache is thought to be generated by nociceptive processes within
      the meninges, followed by activation of trigeminal neurons within the brainstem.
      The noxious stimuli initially involved in these nociceptive processes are
      unknown. A preparation was developed in the barbiturate-anesthetized rat, in
      which the activation of trigeminal brain stem neurons by selective local
      stimulation of the dura mater could be observed. METHODS: The dura mater
      encephali was exposed by trepanizing the parietal bone up to the sagittal
      superior sinus. The surface of the dura was stimulated with electrical pulses
      using bipolar electrodes. Extracellular recordings were made from neurons in the
      subnucleus interpolaris and caudalis of the spinal trigeminal nucleus. Neurons
      driven by meningeal afferents were identified by electrical stimulation and by
      probing their receptive fields on the dura mater. For chemical stimulation a
      combination of several inflammatory mediators (bradykinin, serotonin, histamine
      and prostaglandin E(2), each 10(-4)M, 6.1) was topically applied to the dura
      mater or injected through a catheter into the sagittal sinus. RESULTS: Most of
      the trigeminal brain stem neurons with input from the parietal dura mater had
      convergent input from the facial skin with preponderance of the periorbital
      region. A high proportion of neurons (69%) could be activated by the combination
      of inflammatory mediators administered to the dura mater. CONCLUSION: We conclude
      that chemical stimuli activating the meningeal nociceptive system may play a
      decisive role in the generation of headache. This is particularly relevant for
      the nociceptive processes during neurogenic inflammation, which is believed to be
      an important step in the pathophysiology and development of migraine pain. The
      preparation presented here may be a valuable model for further studying the
      neurophysiological changes that are involved in the generation of headache.

PMID- 12799804
TI  - ["Pain under discussion--stages of chronicity and treatment outcome].
AB  - PROBLEM: "Pain under Discussion" aims at the education of patients with chronic
      headache and back pain by applying a standardized manual with detailed
      instructions for seven sessions in a group setting. Apart from encouraging a
      reconceptualization of the patients' pain experience with reference to a bio
      psycho-social model, the program provides information about the vicious circle of
      pain, avoidance and demoralization and relies heavily on behavioral assumptions
      about the process of chronicity. Patients are offered participation in
      progressive relaxation according to Jacobson, they learn to engage in pleasant
      activities, and are instructed to more and more maintain an upright body position
      during various activities of every day life. The study evaluates the outcome of
      the training. Moreover, as an algorithm for grading pain patients according to
      their level of chronicity has recently been developed by Gerbershagen, we use
      this algorithm in order to investigate the relationship between the outcome of
      treatment and the assigned level of chronicity. In addition, we test the
      assumption that a higher level of chronicity is related to a lower level of
      psychological functioning pre treatment. METHODS: 35 patients with a diagnosis of
      a chronic low back syndrome (Toronto classification) and 30 patients with a
      diagnosis of tension-type headache (IHS classification) have been recruited from
      six facilities specialized in the treatment of chronic pain patients. An average
      pain duration of 11 years indicates a long career as a pain patient. At the
      initial assessment, patients were assigned to three levels of chronicity
      according to the algorithm. Before and six month after completion of the program,
      they were asked to fill in a pain diary and well-established pain questionnaires
      with good psychometric properties under inclusion of pain intensity and control
      over pain (diary) as well as sensory and affective dimensions of pain, coping,
      self-instructions, disability, well-being and depression. RESULTS: Analyses of
      variance indicate a close relationship between a higher level of chronicity and a
      lower degree of psychological functioning. T-Tests for paired samples and
      Bonferroni correction show significant changes in the affective dimension of the
      pain experience, in coping styles and self-instructions, as well as in well
      being, when follow-up data are compared with the initial values. This indicates a
      favorable outcome of the training. Analysis of covariance, on the other hand,
      demonstrate that the outcome does not depend on the level of chronicity at the
      first assessment. CONCLUSION: Irrespective of the initial pain grading of the
      patients the training program has proven to be effective with regard to different
      outcome measures.

PMID- 12799805
TI  - [Alpha 2-adrenergic agonists. Use in chronic pain--a meta-analysis].
AB  - alpha(2)-adrenergic agonists, mimicking the action of the inhibitory transmitter
      norepinephrine, cause antinociception due to postsynaptic inhibition of
      spinothalamic projection neurons, presynaptic inhibition at the central nervous
      system termination of primary sensory nerves, presynaptic inhibition of brainstem
      noradrenergic neurons and a generalized decrease in central nervous system
      sympathetic efferent activity. There is a mutual potentiation of antinociceptive
      effects of clonidine and morphine. Clonidine is used in chronic pain states for
      treatment of neuropathic, neuralgic and deafferentiating pain. Based on a meta
      analysis of the studies published in the years 1996-1996, the therapeutic
      efficacy of systematically administered clonidine was evaluated in chronic pain
      states. Out of 403 screened published studies, only 9 fulfilled the selection
      criteria. Besides three case reports with successful clonidine treatment, four
      placebo-controlled studies could be analyzed treating the following chronic pain
      states: chest pain despite normal coronary angiograms; painful diabetic
      neuropathy; postherpetic neuralgia; hyperalgia in patients with sympathetically
      maintained pain and chronic low back pain. Although three studies demonstrated
      statistically significant improvement in pain scores, the improvement in pain
      relief in these cases was slight. Long-term treatment was successful in a few
      responders over a period of 17 months. Hyperalgesia caused by sympathetically
      maintained pain was relieved by topical (transdermal) application of clonidine.
      Based on this evaluation a grade C recommendation is derived, which relates to
      responders. Successful treatment is expected only in pain states with increased
      sympathetic nervous system activity. Therefore, in chronic pain, treatment with
      systemic clonidine is of no significant value.

PMID- 12799807
TI  - [What is nociceptor].

PMID- 12799806
TI  - [Local therapy with capsaicin or ASS in chronic pain].
AB  - OBJECTIVE: To provide a brief review of the current state of topical treatment
      with capsaicin or acetylsalicylic acid (ASA) for therapy of chronic pain
      syndromes. DATA SOURCES: A MEDLINE search was used to find the pertinent
      literature on "capsaicin" or "ASA" and "chronic pain"; further publications found
      in these articles were added. CONCLUSIONS: Capsaicin is a white crystalline
      parent compound of a group of vanillyl fatty acid amines. Because of its highly
      specific action in neurons it has become an important tool in neuroscience.
      Because of its effects, it is obvious to try for the therapy of circumscribed
      neuropathic pain. Capsaicin acts by depleting stores of substance P and other
      neurotransmitters, resulting in a blockade of a specific group of sensory
      afferents. The corresponding clinical findings are initial burning and a
      desensitization of specific C fiber nociceptors after repeated application. The
      pain relieving potency was observed in various clinical investigations and even
      in a few controlled, double-blind studies about neuropathic pain syndromes and
      (osteo)arthritis. In contrast to these findings, a recent study found no
      significant benefit of capsaicin, probably because this study was the first to
      use an active placebo. Therefore, and because clinical efficacy and advantages
      over other therapies have not been demonstrated up to now, capsaicin cannot be
      classified as standard therapy. It may be a therapeutic option as an alternative
      or as an adjuvant treatment. Pain reduction was also observed after topical
      application of ASA/ether mixture in the one and only controlled double-blind
      study on this issue. Therefore, topical ASA therapy for (post)herpetic neuralgia
      is mainly based on a few enthusiastic case reports rather than on well founded
      investigations. Furthermore, the discrimination of local from systemic effects,
      the toxicological profile of longterm topical treatment, and the mechanism of
      action has not been evaluated. In conclusion, topical ASA cannot be recommended
      for routine clinical use at present.

PMID- 12799808
TI  - [Opioids and driving ability].
AB  - INTRODUCTION: Clinical observations of patients under oral opioid treatment
      suggest that the initially appearing central side effects such as sedation,
      dizziness or drowsiness decrease after a few weeks of treatment. However, it is
      still unclear whether long-term treatment with opioids impairs complex
      psychomotor functions such as driving a car. METHODS: Twenty patients on stable
      dosages of oral opioids were examined using a driving simulator. The patients
      were regular car drivers and not older than 70 years. Additionally, every patient
      had to complete a questionnaire for mental condition and vigilance and the "d II"
      letter cancellation task. Control groups tested in the same way were: patients
      before an elective operation after taking benzodiazepines for sedation,
      volunteers after alcohol consumption (0.80 per thousand ), physicians on call
      with less than 4 h of sleep and healthy volunteers without any medication.
      RESULTS: Some of the patients treated with opioids reacted as fast as medication
      free volunteers. There were no significant differences between the reaction times
      of older patients (>50 years) receiving opioids in comparison to the group of
      older healthy volunteers. The same result was obtained in the letter cancellation
      task. No differences could be seen between medication-free volunteers and
      patients receiving opioids with regard to tasks of visual or motor control
      skills. The volunteers under influence of alcohol and the patients under
      benzodiazepines had a considerable decrease in performance. CONCLUSIONS: Long
      term therapy with opioids does not inevitably impair complex skills, but the
      decision to permit driving a car can only be made in the individual case.
      PRACTICAL RECOMMENDATIONS: At the beginning of therapy with opioids the physician
      has to fulfil his duty to inform the patient of any possible dangers of
      treatment. From the medical point of view, driving must be prohibited until a
      stable opioid dosage is reached. Any changes in dosage (increase, reduction),
      change of the opioid and poor general condition independent of the opioid therapy
      must result in prohibition of car driving. Continuous control of the therapy with
      documentation is a duty of the physician. The written documentation should
      include the patients' physical and mental condition, side effects and the
      therapeutic result. From the medical point of view, driving can be possible when
      dosage treatment and general condition remain stable. In any case, the doctor has
      to remind the patient of the responsibility of critical self-examination. In
      doubt, special performance investigation should be taken into consideration.

PMID- 12799809
TI  - [Influence of postoperative pain therapy on nausea and vomiting].
AB  - PROBLEM: Postoperative nausea and vomiting remains an important problem. Many
      risk factors have been identified; however, the importance of postoperative
      analgesic technique and patient expectation remain poorly defined. METHODS: We
      prospectively collected data on postoperative nausea and vomiting (PONV) in four
      groups of randomly selected patients (n=50 per group) who received either simple
      analgesics, nurse-administered intravenous morphine (NAA), patient-controlled
      analgesia (PCA) with morphine or epidural analgesia with bupivacaine and
      fentanyl. Patients were questioned regarding any past history of PONV or motion
      sickness, their preoperative expectation of suffering PONV and satisfaction with
      their antiemetic therapy. RESULTS: The incidence of nausea was higher in both
      morphine groups P<0.05), women (P<0.05), those less than the median age of their
      group (P<0.05) and those with a past history of PONV (P<0.05) or motion sickness
      (P<0.05). Most patients did not expect to experience PONV (19.3%). The incidence
      of nausea was higher in those expecting to experience PONV than in those not
      expecting to suffer PONV (P<0.01). Of those who received postoperative antiemetic
      treatment, 23.6% were dissatisfied or very dissatisfied with their therapy. Few
      patients received a prophylactic antiemetic drug (15%). CONCLUSIONS: Study
      results show that patient expectation is a potent predictor of postoperative
      nausea, a risk factor hitherto ignored in the anaesthetic literature, and that,
      in the provision of analgesia following major surgery, epidural analgesia is
      associated with less PONV than intravenous morphine.

PMID- 12799810
TI  - [The importance of bodily complaints in patients with chronic back pain].
AB  - Pain perception is a complex psychosomatic phenomenon and is influenced by
      different psychological variables. Apart from their pain perception, chronic pain
      patients also suffer from different bodily complaints. The clinical significance
      of this finding is not yet clear. Bodily complaints in chronic pain patients may
      represent (a) a bodily expression of depressive symptoms, (b) a sign of
      chronicity, and (c) the expression of a heightened bodily awareness in the sense
      of hypochondriasis. METHODS: A psychometric study was done with 83 patients with
      chronic low-back pain. The patients were interviewed and tested psychometrically.
      We administered a German scale to measure bodily complaints (BL), an inventory to
      measure the extent of depressive symptoms (DS) and two subscales of an
      personality inventory (bodily complaints and hypochondriasis). In addition,
      patients were evaluated according to three stages of chronification ("Mainz Pain
      Staging System"). Ten anamnestic variables from four dimensions (temporal
      aspects, spatial aspects, medication usage behavior and patient's health care
      history) are added to yield a total chronification stage with three stages
      ranging from acute to chronic pain. RESULTS: Results indicate that bodily
      complaints have to be interpreted as signs of depressive disorder and chronicity.
      Signs of bodily 'awareness' or 'somatic anxiety'- in the sense of hypochondriasis
      - could not be found. Hypochondriasis does not seem to play a significant role in
      chronification of low back pain. CONCLUSIONS: From a cognitive-behavioral
      perspective the results support the hypothesis that psychological disturbance in
      chronic pain is a cause of long-standing pain perception and the result of the
      chronification process.

PMID- 12799811
TI  - [Do questionnaires for the assessment of change really assess change?].
AB  - PROBLEM: Two methods for the assessment of change are evaluated: (1) subjects'
      ratings of the outcome taken after termination of the treatment, and (2)
      comparison of test scores taken before the beginning and after termination of the
      treatment. METHODS: Included in the analysis are 82 subjects with chronic
      headache and/or back pain who participated in psychological group treatment for
      pain. They were given an outcome rating scale with 15 items (ORS) after therapy
      in addition to pain diaries and questionnaires for the assessment of physical
      symptoms, mood and quality of life. Diaries and questionnaires were filled in
      twice, before and after therapy. RESULTS: The ORS demonstrates satisfying
      psychometric properties. Internal consistency is 0.94 (Cronbach's alpha) and
      retest reliability is 0.74. Correlations of this scale with outcome criteria
      based on pre-post comparisons, however, are mostly nonsignificant. Significant
      correlations are found when the ORS scores are related to the questionnaire
      scores after therapy. CONCLUSION: It is concluded that, contrary to the
      formulation of the items, the ORS scale does not so much assess change, but
      rather depicts the state of the subjects at the time the assessment is made.

PMID- 12799813
TI  - [Potentially life-threatening failure of a portable medication pump].

PMID- 12799812
TI  - [Trigeminal neuralgia as symptom of an infratentorial space-occupying process].
AB  - Despite excellent technical means of imaging the posterior fossa by magnetic
      resonance imaging (MRI), some infratentorial space-occupying processes still
      remain undiscovered, especially if they present only slight symptoms or imitate
      typical different diseases. METHODS: We analysed the data of 334 patients who
      were admitted because of infratentorial space-occupying processes in the years
      1986 to 1995. RESULTS: There were six patients with trigeminal neuralgia caused
      by infratentorial tumors. In only one was the tumour previously diagnosed. All
      suffered from tic douloureux; two had undergone operative treatment. Mean latency
      from first symptoms until diagnosis was 48 months. On admission all patients
      presented at least slight neurological deficits. Postoperatively, the patients
      remained pain-free. CONCLUSION: Because the prognosis of operative treatment and
      the occurrence of postoperative deficits depend on tumour size, we advocate MRI
      examination in every patient presenting tic douloureux, even without additional
      neurological signs.

PMID- 12799814
TI  - [Paracetamol and metamizol in the treatment of chronic pain syndromes].
AB  - In a medline search (covering 1966 to Sept. 1996) 32 clinical studies were
      identified, in which the efficacy of paracetamol or matamizol per se, or in
      comparison to other analgesics, in various chronic pain states, such as migraine,
      dysmenorrhoea, arthritis and osteoarthritis pain and cancer pain had been
      examined. In patients with migraine (4 studies) several other analgesics
      (ibuprofen, mefenamic acid, flupirtin) were slightly more effective than
      paracetamol, however, the efficacy of paracetamol itself had not been assessed.
      In patients with chronic tension headache (1 study) paracetamol was superior to
      placebo, but less effective than naproxen. Pain of dysmenorrhoea was not, or only
      marginally improved by paracetamol in 3 studies, efficacy was reported in 1
      study. Similarly, pain in rheumatoid arthritis was not significantly alleviated
      when paracetamol was given alone (3 studies) and marginally improved, when
      combined with naproxen and tested against naproxen alone (1 study). Some
      improvement by paracetamol of pain scores in patients with osteoarthritis (5
      studies) requires further clinical confirmation. No studies were found, in which
      metamizol had been studied in chronic non-cancer pain. Paracetamol and/or
      metamizol have been included in 14 studies on cancer pain, most of these studies
      attempting to validate the WHO analgesic ladder for cancer pain treatment.
      However, except for one study, in which metamizol was comparable in efficacy to
      morphine, all other publications do not provide detailed information on the
      efficacy of individual analgesics. Therefore it is not possible at present, to
      assess the possible merits of paracetamol or metamizol in the treatment of cancer
      pain from published studies.

PMID- 12799815
TI  - [Ketamine for treatment of chronic pain: meta-analysis].
AB  - The idea of using Ketamine to treat chronic pain is mainly based on the central
      antinoceptive effect of the substance acting as a noncompetitive antagonist at
      the NMDA-receptor. In the present meta analysis over a period from 1/1981 up to
      6/1996 twelve publications (1994-1996), which have dealt the use of Ketamine for
      patients with chronic pain, are evaluated and discussed. The entire positive
      evaluation of the drug is based on the results of the studies under
      consideration. The studies investigating 88 cases are classified, i.e. seven
      studies are assigned to level 3, two studies to level 4, and three studies to
      level 5. A significant reduction of pain has been proven for patients with
      neuropathic pain by four cross-over-studies comparing the drug with placebo.
      However, observations have been restricted to a few hours after the
      administration of the drug. A positive effect of Ketamine as compared with
      opioids has been demonstrated by three studies, one of them with statistical
      significance. Positive long term results have been observed by two studies
      considering the subcutaneous and intravenous application of Ketamine (72-480 mg,
      daily) to 14 cancer pain patients, to whom opioids have been administered with
      insufficient effects before. A successful five-week-application (oral) of
      Ketamine has been described convincingly in a case report of a patient with
      postherpetic neuralgia. Two studies interpret the additional intrathecal
      administration of Ketamine to cancer patients as a possibility of either impeding
      the development of tolerance of the local anesthetic or reducing morphine
      requirements. Only one paper has dealt with the known side effects of Ketamine.
      Here, the therapy had to break off in two cases. In nine cases the side effects
      could be suppressed by Droperidol. For the future, research with more study power
      is necessary to establish Ketamine in the therapy of chronic pain.

PMID- 12799816
TI  - [Idiopathic abdominal pain in children: results, deficits and perspectives of
      empirical research].
AB  - Recurrent abdominal pain (RAP) is one of the most common pain syndromes in
      childhood, with prevalence rates ranging from 10 to 20% in all school-age
      children. In nearly 50% the complaints persist over many years of their life-span
      to adolescence or adulthood. Although the empirical findings have increased in
      the last decade, our knowledge about the etiology, pathogenesis, and
      pathophysiology is still very limited. Current approaches suggest that we
      understand recurrent pain syndromes as a complex and multidimensional disturbance
      (biopsychosocial paradigm). In this respect there is strong evidence for the
      major importance of psychosocial causes (daily hassles, specific life events),
      psychopathological factors (anxiety, depression, somatization disorder), and
      social environmental influences (mother's psychopathology, social modelling,
      reinforcement) in the pathogenesis of functional abdominal pain. The noticeable
      correlation with other pain syndromes and functional disturbances indicates that
      recurrent pain may possibly be a manifestation of a basic somatization disorder.
      The unfavourable long-term prognosis supports the need for early and specific
      interventions. Psychological treatment requires a medical examination to exclude
      organic origins. Some of these invasive diagnostic procedures can be very
      difficult, expensive and distressing for the child. Behavioural medicine is based
      upon having an extensive family history and symptom analysis. The psychological
      interventions applied in clinical practice include prophylaxis, reduction of pain
      symptoms and environmental modification. In recent years there has been an
      increasing trend to create more complex and multidimensional behavioural
      treatment programs for children. Although preliminary data on the use of these
      behavioural medicine programs have shown some promise, further investigations are
      needed to examine the applicability and effectiveness of specific interventions
      in the treatment of abdominal pain symptoms.

PMID- 12799817
TI  - [Legal aspects of intoxicating medication in relation to traffic safety].
AB  - When a patient operates a vehicle, he commits a traffic violation if he is
      incapable of conducting his vehicle safely in traffic at that time. If the lack
      of safety has been caused by medication or other types of intoxicating drugs, he
      commits a criminal offense. At present, scientific evidence suggests that the
      proof of a causal link between driving insecurities and the intake of
      intoxicating medication cannot solely be based upon the quality and quantity of
      such medication but must also take into account the possible establishment of
      visible physical disabilities.A physician must thoroughly inform his patient of
      all relevant risks both of the illness itself and its medical treatment in
      relation to traffic safety. The former is nevertheless not legally authorized to
      suspend the patient's driving licence; neither does his explicit permission to
      operate a vehicle generally protect the patient from criminal prosecution. Even
      in cases where the capability to operate a vehicle is not subject to medical
      doubts, a patient should be encouraged to constantly scrutinize this capability,
      especially in regard to unexpected side-effects of the medication. Insufficient
      medical advice may result in criminal responsibility of the physician if an
      accident is proved to have been caused by the patient, resulting in injury of the
      patient or a third party. If sufficient advice has been conveyed, possible
      criminal responsibility is limited to cases where the patient lacks the ability
      to act self-responsibly or if there is the imminent danger of an accident. If the
      physician learns that a patient with relevant disabilities will attempt to
      conduct a vehicle despite his opposite advice, he may inform the traffic
      authority after having repeatedly and unsuccessfully communicated with the
      patient and after having carefully balanced the interests of the parties
      involved. The physician is then longer obliged to abide by the requirement of
      medical confidentiality; there is, however, no legal obligation to report to the
      traffic authority.

PMID- 12799818
TI  - [Long-term follow-up after participation in an integrated group treatment program
      for patients with intractable musculoskeletal pain].
AB  - METHODS: Long-term outcome in terms of well-being, depression and ability to cope
      was evaluated by means of a mailed questionnaire up to 5 years after
      participation in an integrated group treatment program for chronic
      musculoskeletal pain (mostly back pain). Sixty-one completed questionnaires were
      available for analysis, representing 69% of all 89 participants. RESULTS:
      Comparison of responders and non-responders yielded no important differences. On
      the basis of their further need for treatment, their working ability and global
      rating of outcome, patients were divided into three groups: In 18 cases the
      situation had further improved, 33 were unchanged and 10 had worsened.
      Sociodemographic data and pain history did not differ among the three groups.
      Patients with a favorable outcome scored significantly lower than the rest of the
      patients on a symptom check list and showed the greatest decrease from
      pretreatment values (if available). They rated themselves significantly higher on
      the two-dimensional health locus of control scale and were aware of significantly
      more factors influencing their pain than were the unimproved (unchanged or
      worsened) patients. Cognitive-behavioral strategies had been continued long-term
      by 83.6% of the patients and were rated most helpful. Physical training and at
      least one relaxation technique were continued in 80.3% of the patients, with a
      slightly lower rating of helpfulness. Improved patients gave generally higher
      ratings for helpfulness and applied these strategies also to problems other than
      pain (e.g. anxiety). CONCLUSIONS: The majority of patients maintained at least
      two of the self-help strategies over many years and seem to profit from their
      use. Positive long-term effects on well-being were visible in 30% of all
      participants, and these were clearly more orientated towards self-control than
      the unimproved subgroups.

PMID- 12799819
TI  - [Influences on the outcome of lumbar disc-surgery].
AB  - In a prospective study 30 patients suffering from a lumbar disc-prolapse and
      typical neurological symptoms were examined with regard to the predictors of the
      outcome 15 months postoperatively. Alongside the clinical examination and the
      raising of illness-anamnesis the Giessen pain questionnaire (Giessener Beschwerde
      Bogen), the Giessen-Test, the Freiburg Personality Inventory (Freiburger
      Personlichkeits-Inventar), the Mainz pain questionnaire und a pain scale were
      used. By means of the pain questionnaires two groups were formed. Patients
      without (N=15) and patients with (N=14) postoperative impairment. On the basis of
      selected scales of the Giessen pain questionnaire and the characteristic
      "psychosomatic disorder in the anamnesis" for 90% of the patients the outcome
      could be correctly predicted. For the estimation of the outcome by means of the
      estimation of global functioning level the likelihood of correct prediction was
      83%. Medical and demographic parameters as well as the other results of
      psychological testing did not correlate with the outcome. The great importance of
      psychosomatic factors in a wider sense for the outcome is found to be confirmed
      in the literature. The significance of this result for the coping is debated with
      a background of the concept of "somatizing" versus "symbolizing". The conditions
      in therapy should lower psychological stress in order to reduce the necessity for
      "somatization" and facilitate "symbolization". This is specified as well for the
      treatment in regular surgical departments as for specialized pain-programs.

PMID- 12799820
TI  - [Acupuncture together with cytokine depressing herbs in comparison to injection
      therapy with steroids in sciatic pain].
AB  - INTRODUCTION: Because of their frequency and consequences sciatica remains a
      demanding clinical entity with significant social and economical impact. There is
      a high demand on therapeutic modalities, using folk medicine methods in the
      treatment of orthopaedic diseases. No data is available on the usefulness of
      methods like natural herbs in combination with acupuncture. Aim of our study was
      to present data on the effect of acupuncture and cytokine-inhibiting natural
      herbs in sciatic pain. We compared these results with nerve root infiltration by
      local anaesthetics and corticosteroids in our orthopaedic outpatient clinic.
      MATERIALS AND RESULTS: 278 patients with chronic pain for at least 3 months were
      observed. All three therapeutical modalities showed improvement of pain scores.
      Best results were gained with steroid injection ( n=26; 66% pain reduction),
      acupuncture in combination with herbs improved the pain in average of 62% (
      n=230), whereas injection with local anaesthetic had a pain reduction of 48% (
      n=22). Sole Mepivacain-HCl treatment had significant less pain reduction compared
      to the other treatment modalities. CONCLUSION: According to our results
      acupuncture in combination with herbs and steroid nerve blocks appear to be an
      effective and thus recommendable conservative therapy in cases of sciatic pain.
      Taking into account that patients increasingly prefer ethnomedical modalities of
      treatment our study gains importance for practising orthopaedists.

PMID- 12799822
TI  - [Chronic pain treatment with antidepressants--metaanalysis].
AB  - Both preclinical and clinical evidence support the usefulness of antidepressants
      in chronic pain treatment. Monoamine uptake inhibitors influence the
      neurotransmissions of noradrenaline (NA) and/or serotonin (5-HT); their effect on
      nociception is thought to take place predominantly within the spinal cord.
      Antidepressant drugs seem to differ in their properties as analgesics and as
      thymoleptics. The present work is aimed at correlating the special mechanism of
      action of antidepressants in diminishing nocicepetion with the pharmacological
      profile of these drugs in clinical pain treatment. From a preclinical,
      experimental point of view, it can be expected, that mixed type uptake blockers
      should be superior to selective NA or 5-HT uptake inhibitors. The analgesic
      profile of antidepressants was established by a metaanalysis of clinical trials
      on the effect of these drugs, given alone or in combination with other
      analgetics, in chronic pain syndromes. 57 Clinical trials were separated into 5
      groups according to their scientific quality: [1] placebo-controlled double-blind
      studies with high power; [2] placebo-controlled double-blind studies with low
      power; [3-4] open controlled studies or studies with historical controls; [5]
      case reports. A study was positive if the tested antidepressant was more
      effective than placebo or the compared drug or seemed beneficial with respect to
      the interval of its previous absence. The most effective antidepressants in
      chronic pain treatment only included unselective monoamine reuptake inhibitors in
      the following rank order: amitriptyline > clomipramine > or = desipramine > or =
      imipramine > or = doxepin. A statement about the appropriate dosage of these
      drugs in chronic pain treatment, however, must wait for properly conducted dose
      finding studies which include the measurement of plasma concentrations.

PMID- 12799821
TI  - [Postoperative epidural analgesia with Bupivacaine-HCl 0.06%/Fentanyl 0.0002%.
      Experiences and physicochemical stability in infusion bags].
AB  - Continuous epidural infusion of bupivacaine with the opioid fentanyl represents
      an effective analgesic method in the therapy of strong postoperative pain after
      major surgery. Preparation of the required infusion solution in syringes with a
      volume of 50 ml immediately prior to administration is routinely performed by
      nursing staff in Germany. The effort required for the preparation is associated
      with logistical and pharmaceutical difficulties. The preparation of a mixture of
      bupivacaine hydrochloride 0.06% and fentanyl 0.0002% in 250 ml infusion bags at
      the pharmacy of the University Hospital Mainz is described. To determine the
      physicochemical stability, the concentration of bupivacaine-HCl and fentanyl was
      assessed using HPLC over a period of 32 days; in addition the pH values were
      determined. After 32 days 95% of the bupivacaine hydrochloride and fentanyl
      baseline values were recorded. The pH baseline value had decreased from 5.48-5.52
      to 0.5-0.7 units. The measured values confirm the physicochemical stability of
      the mixture of bupivacaine hydrochloride 0.06% and fentanyl 0.0002% over a period
      of 32 days. The infusion bag can be stored for 4 weeks at room temperature.

PMID- 12799823
TI  - [Craniomandibular disorders. Conception of a screening method for patients with
      chronic head and facial pain].
AB  - Craniomandibular disorders are suggested to be responsible for many cases of
      chronic pain of the head and face. The assessment of dysfunctional factors in
      diseases of chronic head and facial pain normally requires special knowledge and
      equipment for the diagnosis and therapy of stomatognathic dysfunction. However,
      the first signs can be evaluated rather well without using complete equipment,
      which is not always available in general practice. It is therefore important that
      general practitioners have a simple, time-efficient method of routine screening
      based on sufficient methods and tests. Thus, we would like to present a
      questionnaire consisting of ten points that cover the valid elements of complete
      stomatognathic assessment. Answering these questions reveals signs of
      dysfunctional components of craniomandibular disorders, which indicate a
      dysfunction diagnosis and even better, consultation with a specialist.

PMID- 12799824
TI  - [Pain intensity, mood and pain-alleviating actions in pre-chronic low back pain
      patients].
AB  - INTRODUCTION: The present study examines the correlations between pain intensity,
      mood and pain-alleviating actions in pre-chronic low back pain patients. The
      three variables were obtained with the Ulm Pain Diary (Ulmer Schmerztagebuch,
      UST). METHODS: Thirty-eight patients with low back pain described pain intensity,
      effect of pain on mood and medication as well as other therapies over a 3-week
      period (21 days). The patients had a history of pain for between 6 weeks and 6
      months. Clinical and orthopedic examinations revealed no relevant organic
      findings explaining the pain process. RESULTS: Pain occurred on 18.1 (of 21)
      days. Half of the patients (n=19) used medication or took other actions against
      their pain. Correlations between the three variables demonstrated that all three
      were significantly related. Partial correlations showed in addition to a high
      correlation between pain intensity and mood, that the frequency of pain-relieving
      actions was far less related to pain intensity than to mood. The group that took
      actions against their pain had a higher level of pain intensity than the no
      action group. Furthermore, the effect of pain on mood was significantly greater
      in this group than in the no-action group. CONCLUSION: The findings indicate that
      pain intensity, mood and actions against pain are highly correlated. When pain
      intensity is statistically controlled, the influence of mood on taking medication
      or other actions against pain becomes more pronounced. It can be concluded that
      self-initiated actions against pain depend much more on mood than on pain
      intensity in pre-chronic low back pain patients.

PMID- 12799825
TI  - [Active music therapy for chronic pain: a prospective study].
AB  - There are only few publications about the effect of music therapy on pain relief.
      The intention of this prospective study is to demonstrate the influence of the
      Nordoff/Robbins method of active music therapy in a group of 12 patients with
      fibromyalgia, myofascial pain syndromes and polyarthritis on pain reduction, life
      quality and coping. The clinical parameters of each patient were related to the
      observations in the audio- and video-documented music therapy settings and to the
      self-reported changes in pain intensity and pain behaviour. There was a
      significant reduction of pain intensity and pain-related disability in the music
      group compared to a control group, but no change in the depression and anxiety
      score. The influence of music therapy could be even better demonstrated in the
      systematic analysis of the single cases by individual profiles. Active music
      therapy affects especially the communicative and emotional dimension of chronic
      pain. Psychophysiological and psychodynamic models are presented to explain the
      effectiveness of music therapy on pain reduction. Clinical studies on music
      therapy as well as on other "art therapies" should relate the analysis of
      clinical parameters to the descriptive-phenomenological documentation of the
      therapeutic process to demonstrate systematically the influence of music and art
      in the individual case.

PMID- 12799826
TI  - [Outpatient management of chronic pain in Middle Franconia].
AB  - In Middle Franconia, one of the larger Bavarian administrative division
      (population 1994: 1,657,101), the number of patients suffering from cancer pain,
      chronic headache and chronic back pain is not known. Furthermore, there are no
      data on interdisciplinary organization of outpatient pain management. METHODS:
      All physicians and psychologists involved in outpatient pain management in Middle
      Franconia (n=2130) were asked (questionnaires) to estimate the number of patients
      suffering from cancer pain, chronic (>6 months) headache and chronic (>6 months)
      back pain treated the last 12 months. RESULTS: 264 (12.4%) responses were
      analyzed; 107,346 patients had been treated in the last 12 months, 67% by a
      single specialist and 33% by two or more specialists. The participation of
      psychotherapists and anesthetists in outpatient management of pain patients was
      poor; 22,754 (21%) patients were thought to need multidisciplinary analgesia
      therapy in a pain clinic, which actually does not exist in Middle Franconia.
      CONCLUSION: The data presented suggest that patients suffering from chronic pain
      are not optimally managed in Middle Franconia. Regional institutions for
      multidisciplinary pain treatment have to be established close to where chronic
      pain patients live.

PMID- 12799827
TI  - [A pilot investigation into the effects of extracorporeal shock waves on muscular
      dysfunction in children with spastic movement disorders].
AB  - INTRODUCTION: Extracorporeal shock waves (ESW) are being used increasingly
      frequently for the treatment of narrowly localized pain in the musculoskeletal
      system. Pain is normally associated with muscular dysfunction. Beginning with the
      observation that not only is the pain soothed by treatment with ESW, but that the
      muscular dysfunction itself is relieved, an attempt has been made to treat the
      impaired function in cases of infantile cerebral palsy with ESW. METHOD: In 35
      children and young people with mainly spastic disturbances of movement, the
      bellies of those muscles producing the flexion contracture of the lower limb were
      each treated with 500 non-focused pulses of low-energy ESW. The focus (focal
      pressure 10 MPA=0.06 mJ/mm) of the shock waves itself was placed either within
      the coupling cushion of the therapy source (Minilith, Storz Medical, CH
      Kreuzlingen) or obliquely outside the patient's body. In this way ESW could be
      dispersed throughout the muscles and the risk of undesirable effects was
      minimized. The energy used amounted to about 30% of the threshold value at which
      cellular damage from focused treatment with ESW had been observed in the
      endothelium of the human umbilical cord. RESULTS: The degree of movement at the
      hip joint increased after one treatment by an average of 17 degrees, at the knee
      joint by 12.3 degrees and at the ankle joint by 7.1 degrees, each increase being
      statistically significant. Muscular stiffness, spastic co-contractions, and
      myofascial viscoelasticity, as well as dyskinetic and ataxic symptoms, decreased.
      It appeared as if a systemic action had entered into the motor control. Together
      with an increase in general proprioception, there was an improvement in body
      image, in economy of movement and also in the limbs that had not been treated. A
      few patients showed euphoric reactions for about 2 days after treatment. No
      undesirable effects were observed during a follow-up of 12 months. The treatment
      was painless and is therefore suitable for children. The biomechanical
      improvement remained for several weeks and this time could be used for initiating
      an improved pattern of movement. CONCLUSION: ESW is suitable for use as an
      additional instrument for physiotherapeutic treatment of infantile cerebral
      palsy. The effective action of ESW on disturbed peripheral muscles has been
      discussed in terms of positive pressure and tensile wave forces and/or forces
      acting by cavitation. The results obtained in this pilot investigation showed
      particular a decrease in muscle stiffness. A controlled investigation with gait
      analysis and psychological control is to be undertaken.

PMID- 12799828
TI  - [Therapy of meralgia paresthetica with acupuncture. Two case reports].
AB  - The authors demonstrate a way to treat meralgia paresthetica ("jeans disease")
      with acupuncture. Two patients with therapy-resistant chronic pain and
      paresthesia of the lateral thigh became free of symptoms quickly and remained
      under acupuncture therapy. Gynecological, vertebral and urological factors must
      be excluded before any kind of symptomatic therapy is begun. The advantages and
      disadvantages of acupuncture are discussed.

PMID- 12799829
TI  - [Pain management in patients with chronic rheumatic pain--a model for primary
      medical care].
AB  - A rheumatologist and a medical psychotherapist collaborate in offering
      periodically a cognitive behavioral treatment program for pain control for the
      patients of a rheumatological practice. The program consists of a biopsychosocial
      model of chronic pain, individualized relaxation training combining progressive
      muscle relaxation and some elements of autogenous training and meditation,
      several attention-related techniques and cognitive restructuring. From 1993 to
      1995, 50 patients took part in five training courses. The compliance of the
      patients was satisfactory and the drop-out rate low (8%). In a post hoc interview
      4 weeks later and another 2 years after the end of the training most of the
      patients assessed the program as useful for reduction of pain, increase of
      activity and enhancement of mood. Psychotherapeutic experience in group therapy
      or special training for non-psychotherapeutic physicians with continuous
      supervision is necessary in order to conduct a qualified treatment program.
      Within medical primary care, rheumatologists can motivate their patients towards
      active pain management, which can help to prepare patients for further
      psychotherapy in cases with psychiatric disorders and/or severe psychosocial
      strains.

PMID- 12799830
TI  - [Quality assurance in chronic pain therapy. Results obtained by a task force of
      the German Chapter of the International Association for the Study of Pain on
      psychological Assessment of chronic Pain. Psychological instruments for the
      assessment of pediatric pain].
AB  - The present paper is one in a series of publications reviewing German instruments
      for the psychological assessment of pain. Part X deals with pain measurement of
      acute and chronic pain in infants and children. German assessment instruments of
      pediatric pain together with frequently used instruments of American origin are
      examined and described. The survey contains self-report and behavioral pain
      measures. Multidimensional pain interviews for both children and parents, diaries
      and rating scales, as well as observation measures especially for infants, are
      examined. Since the selection of pain-assessment instruments is dependent on the
      age and cognitive level of the children, for each instrument a minimum age limit
      is given. In cases in which quantitative indices of reliability, validity and
      objectivity are still needed, the evaluation is based on qualitative quotations.

PMID- 12799831
TI  - [General standards in acupuncture treatment of chronic pain].
AB  - General standards in acupuncture treatment of chronic pain are outlined in detail
      in this article.

PMID- 12799832
TI  - [Acupuncture for headache].
AB  - Acupuncture is being increasingly used as one of the most important non
      pharmacological therapies in treatment of chronic pain. Chronic headache,
      especially migraine and tension headache are diseases frequently encountered. In
      their treatment acupuncture is a method with very few side effects and is a
      remarkable alternative or addition in the whole concept of treatment. Open and
      placebo-controlled studies have shown that acupuncture reduces the frequency and
      intensity of headache in many patients, as well as the use of drugs. The success
      rates achieved of about 50-85% are comparable to the results of other methods. In
      the case of migraine, especially good results are archived by prophylactic
      treatment with acupuncture during the pain-free period. The concept of treatment
      depends on the basic rules of traditional Chinese medicine (TCM). Selection of
      the acupuncture points is primarily determined by the pain site. Long-term
      success could be confirmed by follow-up examinations six to eighteen months after
      end of the therapy.

PMID- 12799833
TI  - [Acupuncture in anesthesia or analgesic-induced nausea and vomiting].
AB  - The most common and distressing symptoms following anesthesia and surgery are
      pain and emetic problems. Under most circumstances, pain causes the greater
      amount of suffering, particularly after major surgery, but in some instances
      postoperative nausea and vomiting (PONV) may be more distressing, particularly
      after minor surgery. In outpatient surgery, emesis may also have important
      economic implications, for example, admission to hospital beds because of
      intractable vomiting. Antimetic drugs given during the perioperative period may
      be associated with unwanted side effects, including sedation, hypotension and
      extrapyramidal reactions. Since 1986 there have been studies reporting beneficial
      antiemetic effects for Pe 6 stimulation on the right or both forearms in adults
      using either needling (acupuncture) or pressure (acupressure). The majority of
      these studies have investigated postoperative nausea and vomiting. But Pe 6
      stimulation has also been shown to be an effective antiemetic for symptoms
      associated with pregnancy and chemotherapy. Although Pe 6 electro-acupuncture and
      acupressure are recognized as having an antiemetic effect, its inconvenient
      instrumentation may limit its clinical applicability. There have also been
      studies reporting beneficial antiemetic effects of P 6 acupoint injection with
      50% glucose and acupuncture of the ear.

PMID- 12799834
TI  - [Adverse reactions to acupuncture].
AB  - Acupuncture is frequently used as an alternative therapy to drugs in the
      treatment of pain patients. In this review we discuss adverse reactions to
      acupuncture by means of case reports and our own clinical experience. Frequent
      side effects of acupuncture are local pain, autonomic nervous system reactions
      (including fainting) and small local bleeding or hematomas. There are, however,
      some case reports of serious adverse reactions. Since 1980, there have been 18
      pneumothoraces post acupuncture therapy reported in the literature. Hepatitis due
      to inadequate hygiene standards has also been reported. Some patients with
      valvular heart disease have developed endocarditis after acupuncture. Ear
      acupuncture with permanent needles can cause chondritis or perichondritis. For
      any acupuncture treatment, a careful case history and exact diagnosis are
      necessary. In particular, it should be determined whether wound-healing
      disorders, immunosuppression, coagulation defects, valvular heart disease or
      pregnancy are present, as all of these constitute relative contraindications to
      acupuncture. Hygiene standards have to be observed. Bearing these points in mind,
      acupuncture is a reliable method with few side effects.

PMID- 12799835
TI  - [Acupuncture and reflex sympathetic dystrophy].
AB  - The term "reflex sympathetic dystrophy" (RSD) is used for various syndromes, e.g.
      posttraumatic edema, shoulder-hand syndrome, algodystrophy and causalgia. The
      clinical symptoms of RSD are characterized by a triad of autonomic, sensory and
      motor disturbances, which usually develop in the distal region of an affected
      extremity. The main symptoms are swelling, a side difference in skin temperature
      (autonomic symptoms), reduced active movements and muscular strength (motor
      symptoms) and spontaneous, deep, diffuse pain with an orthostatic component
      (sensory system). As soon as possible the treatment of RSD should include
      sympatholytic strategies and obligatory physical therapy. Acupuncture has also
      been reported to reduce sympathetic activity. The analgesic effect of acupuncture
      is well known, and therefore from an at least theoretical point of view, it
      should make sense to use acupuncture in the treatment of RSD. To date, however,
      no prospective, randomized, controlled, clinical long-term studies have been
      done. One short-term study showed promising results, but did not reach
      statistical significance. In that study acupuncture treatment seemed to alleviate
      the major symptoms of RSD. Since acupuncture rarely has side effects, its role as
      an additional option in the treatment of RSD should be further investigated.

PMID- 12799836
TI  - [Acupuncture for pain in locomotive disorders. Critical analysis of clinical
      studies with respect to the quality of acupuncture in particular].
AB  - 88 clinical acupuncture studies concerning the treatment of locomotive disorders
      are compared. The studies are evaluated according to treatment quality and
      categorised into 6 categories. For the assessment of acupuncture treatment
      quality minimal criteria are defined: reporting the duration of one acupuncture
      treatment (at least 15 min.), reporting the frequency of acupuncture treatments
      (at least 10 sessions before cancelling the therapy), exact description of used
      acupuncture points. Without respect to biostatistical and therapeutical
      qualities, 75 of 88 studies (85.2%) showed positive results for the acupuncture
      treatment. None of the 16 studies, that met the minimal criteria we defined,
      could prove that acupuncture is non-effective. Only two of the 16 studies are
      controlled trials. Our results were compared with those of meta-analytical
      reviews, which discussed acupuncture studies solely on the basis of the
      biometrical aspects. In comparison to conventional orthopedic therapies, certain
      locomotive disorders are recommended for acupuncture therapy.

PMID- 12799837
TI  - [Multidisciplinary treatment program on chronic low back pain, part 4. Prognosis
      of treatment outcome and final conclusions].
AB  - PROBLEM: Studies using a multimodal approach in order to prognose therapeutic
      success in patients suffering from back pain were seen to have highly diverse
      results. However, in spite of various independent health care systems, a common
      interest prevails in identifying determinants of therapeutic success in order to
      improve therapy. METHODS: Ninety disabled patients with chronic low back pain
      were admitted to an 8-week out-patient program of functional restoration and
      behavioral support. The program consisted of a pre-program (education, stretching
      and calisthenic exercises 4 h a day, three times a week for 3 weeks) and an
      intensive treatment period (physical exercises, back school education, cognitive
      behavioral group therapy, relaxation training, occupational therapy,
      socioeconomic and vocational counseling) which took place for 5 weeks, 7 h a day
      as an outpatient program. The program's philosophy encourages active effort on
      the patients' part in order to improve their functional status within a
      therapeutic environment. This reinforces behavior conducive to getting well,
      enhances the patients' sense of self-control over their pain and the resulting
      disability. The main therapeutic target was to facilitate the patients' return to
      work. Apart from medical examination and personal interview, the patients'
      physical impairment, pain descriptions, and psychological distress were also
      measured. This included variables such as depression, psychovegetative
      complaints, quality of life and workplace satisfaction, disability, and coping
      with disease. Measurements were repeated at the end of the 8-week program, and
      following 6 and 12 month intervals. The reliability of prognostic factors in
      predicting treatment outcome (return to work, reduction of pain intensity, self
      assessment of success by the patients) was tested by analyses of variance and
      discriminant function analyses. RESULTS: Patients' return to the workplace could
      be predicted in 85% of cases based on whether an application for pension had been
      made, on the length of duration of work disability, and on "fixed" assumptions on
      the part of the patient concerning his work situation. Pre-treatment somatic
      findings (for example, diagnosis, degree of physical impairment, and functional
      debilities), together with depressive and psychovegetative reactions, were shown
      to have no connection with the patient's ability to return to the workplace.
      Similar findings were demonstrated for the prediction of pain reduction and
      patient satisfaction with treatment. CONCLUSIONS: Predicting successful treatment
      is hardly possible without analyzing individual circumstances, focusing on
      sociodemographic variables, workplace-related conditions, and aspects of
      individual motivation. With regard to objective therapeutic success, subjective
      perceptions proved highly influential. Treatment proved successful only when the
      patient's perception of functional disability was minimized. Hence, individual
      perceptions and experiences were more important than physical capabilities.

PMID- 12799838
TI  - [Supply of opioid analgesics to outpatients with cancer pain].
AB  - INTRODUCTION: Treatment of chronic cancer pain with strong opioids is indicated
      in about 60-70 % of patients. Surprisingly, these very potent analgesics are
      prescribed with great reservations in many countries, including Germany. The aim
      of our investigation was to analyse the supply of opioid analgesics to
      outpatients with cancer pain in the region of Hannover, which has about 1.1
      million inhabitants. METHODS: In Germany special prescription forms, i. e.
      triplicate forms, have to be used for the prescription of strong opioids. At the
      time when our investigation took place prescriptions for outpatients had to be
      renewed every 7 days. For two observation periods of 6 months lasting from
      January to June 1988 and from January to June 1991 all of the opioid prescription
      forms that had been issued by general practitioners for clients of the AOK
      Hannover (one of the major medical insurance companies) were evaluated. The
      reasons for prescribing opioids were analysed by recording the diagnosis. The
      individual treatment period on an outpatient basis during these 6 months was
      determined, excluding, e. g. days of hospitalization. RESULTS: During the two
      observation periods only 16.2 % (1988) and 19.5 % (1991) of the practitioners in
      the region of Hannover prescribed strong opioids to outpatients. The majority of
      the practitioners consisted of general practitioners and specialists in internal
      medicine. Although these two groups mainly function as family doctors who are
      responsible for the basic therapeutical needs of their patients, only 22.6-33.8 %
      of these doctors prescribed opioids to outpatients. In two-thirds of the
      patients, cancer pain was the reason for prescribing the drug. The total number
      of patients with a prescription for cancer pain was 164 in 1988 and 196 in 1991.
      Altogether 1002 prescription forms in 1988 and 1065 prescription forms in 1991
      had been issued for these patients. Applied to the individual treatment period as
      an outpatient, only 36.0 % of the patients in 1988 and 32.1 % in 1991 received a
      regular prescription of strong opioids every 7 days. The mean time interval
      between separate prescriptions was 16.8 +/- 25.4 days in 1988 and 19.4 +/- 29.1
      days in 1991. Accordingly, the majority of patients with chronic cancer pain had
      been supplied with opioids only occasionally. CONCLUSION: Our data indicate a
      significant undertreatment of outpatients suffering from cancer pain. Taking into
      account the estimated total number of patients suffering from cancer, only 14.5 %
      (1988) and 19.0 % (1991) of all outpatients in need of strong opioids were
      supplied sufficiently with those analgesics. Comparing the results from the
      observation period in 1988 with the results from 1991 it becomes obvious that the
      situation has not changed. There are different reasons for the insufficiency of
      opioid treatment: many physicians as well as their patients are still afraid of
      the side effects of strong opioids. Therefore, it is necessary to improve
      education concerning this issue. The legal restrictions on the use of narcotics
      and their complexity are another important reason for doctors not to prescribe
      strong opioids. In 1993 the regulations were simplified; nevertheless, this has
      not led to a profound change in the attitude of the prescribing practitioners.
      Thus, further changes in legislation seem to be necessary so that the
      requirements for the prescription of strong opioids do not differ from other
      drugs.

PMID- 12799839
TI  - [Prescribing strong opioids for pain therapy and for substitution therapy by
      established physicians].
AB  - The prescription of strong opioid by general practitioners was studied,
      particularly for the treatment of chronic pain. In a medium-sized town (around
      250 000 inhabitants) 17,839 prescriptions of strong opioids were issued by 455
      doctors over 5 years (1 January 1990 until 31 December 1994) to 1,939 patients.
      Of these patients 37.8-48.3 % of them received only one prescription for 6
      months, 60.5-75.8 % received between 1 and 4 prescriptions for 6 months, and only
      20.9-35.7 % of all patients received 5 or more prescriptions for 6 months. The
      amount of strong opioids prescribed for cancer pain relief seems to be almost the
      same in 1992 as 10 years ago. The consumption of oral morphine has steadily
      increased compared to 1982 and constitutes almost one-half of all narcotics
      prescribed for pain treatment by general practitioners. For pain treatment the
      value of strong opioids is recognized by both patients and physicians in contrast
      to the prescription of levomethadone as substitution therapy for drug-addicted
      patients. The 6.7 % of the physicians who participated in methadone substitution
      therapy prescribed more strong opioids (52.4 % of prescriptions) than all other
      physicians together prescribe for pain treatment. In order to safeguard the
      quality of medical care for pain treatment by strong opioid analgesics, unbiased
      training of physicians and a clear definition of narcotics is required. It is
      suggested that the expression "narcotic prescription" be changed related to the
      legislative terminology in the pharmacology-related expression "analgesic
      prescription". The prescribing regulations should not constrain medical
      treatment, but create a basic rule for the prescription of strong opioids.

PMID- 12799840
TI  - [Practical and safe prescription of controlled drugs to patients with chronic
      pain].
AB  - The present legal requirements for the prescription of controlled drugs remains
      an impediment to adequate therapy for chronic pain because of an abundance of
      legal regulations. The physician prescribing opioids must consider the permitted
      maximum amount per prescription, the period of time the drug is prescribed for,
      numerous cross references, and other special regulations, and he still cannot be
      sure that he does not violate certain legal requirements. Often these
      difficulties result in withholding necessary pain treatment! In the authors'
      opinion it should be sufficient to write a specific prescription form for
      controlled drugs in the same way as any other ordinary prescription without
      jeopardizing the safety of the drug control system. It is important that the use
      of the narcotic be justified in the sense of paragraph 13 Abs. 1 of the drug
      control regulation, as judged by the responsible prescriber of the drug, and that
      any offence be punished. The use of triplicate prescriptions guarantees
      sufficient proof. Legislation is requested that will substitute for the present
      drug control regulations, which are difficult to handle.

PMID- 12799841
TI  - [Pain therapy with analgesics according to German law--legal aspects].
AB  - Rules still valid today continue the tradition of state narcotics control,
      conceding therapeutic decisions to the physician, but at the same time allowing
      only restrictive use of narcotics. Legal control of medically indicated use of
      narcotics is burdened with conflicts. Recently, physicians have been given more
      scope in the use of strong opioids for pain therapy. Existing limits for a dose
      of opioids may be exceeded when necessary. However, there are still formal rules
      in the German Narcotics Drug Act.

PMID- 12799842
TI  - [Legal and epidemiological aspects of strong opioids].
AB  - In spite of the fact that the treatment of pain is highly developed, outpatient
      care of patients suffering from chronic pain is frequently insufficient. In
      particular general practitioners often refrain from prescribing the necessary
      pain therapy with opioids. Because of the contract regarding medical treatment,
      however, the patient has a legal claim to adequate pain treatment, if necessary
      by administration of opioids. The failure to meet this claim may not only give
      rise to a claim for damages towards the doctor, but even to a charge of bodily
      injury. In comparison, charging the physician with criminal behavior on the basis
      of the Narcotics Act is rather unlikely. Negligent or incorrect prescription of
      narcotic drugs does not constitute criminal behavior, but an administrative
      offence. Even this is hardly something which the physician has to fear. Any
      medically necessary administration of opioids is covered by the Narcotics
      Prescription Ordinance. The narcotics prescription form, however, remains
      indispensable for the safety in the use of narcotics. The doctor's prescription
      alone is obviously not sufficient to curb the considerable abuse of
      pharmaceutical products among the population. In the course of the introduction
      of EDP-readable narcotics prescription form as of 1 July 1995, however, the
      issuing of this kind of prescription was further simplified. Handwritten
      particulars will soon be entirely a thing of the past. Now that the legal and
      administrative conditions for prescribing opioids have been consolidated, the
      main objective is to exhaust the possibilities of prescription for the benefit of
      patients suffering from pain in a better way. This is first and foremost, an
      organizational and technical task of the medical professional group. In
      particular, training and continuing education in the field of pain therapy must
      be further developed without delay.

PMID- 12799843
TI  - [The prescription of opioids from the point of view of clinical and market
      research].
AB  - According to WHO guidelines, morphine is the first choice for the treatment of
      chronic cancer pain, preferably as a controlled-release preparation administered
      orally. The WHO classifies the quality of pain management of a particular country
      by its morphine consumption for medical reasons. For this article, data from
      clinical and market research were collected. In Germany, the amount of morphine
      prescribed is low, both in the total quantity of morphine prescribed and related
      to the individual patient treated. Also the number of patients receiving opioid
      prescriptions is low. In a longitudinal evaluation of general practitioners'
      prescription practices, only 0.1 % out of 1,218,436 patients were given a
      controlled opioid prescription. Only 0.04 % of more than 16 million prescriptions
      were opioid prescriptions. Only 1.2 % of 47,252 cancer patients received a strong
      opioid. The reasons for this low use of opioids are to be found in the special
      regulations for controlled drugs, specified by German narcotic drug legislation.
      The report also focuses on physicians' subjective viewpoints and prejudices. When
      strong opioids are only rarely prescribed, a general practitioner then has
      difficulties in assessing pain and possible side effects and treatment
      evaluation. Clinical research, too, is hampered by special regulations concerning
      controlled opioid administration.

PMID- 12799844
TI  - [Multidisciplinary treatment program on chronic low back pain, part 3.
      Psychosocial aspects].
AB  - PROBLEM: The majority of authors agree today that psychosocial factors have more
      influence on a successful treatment of chronic back pain than other variables, in
      particular medical findings. Therefore treatments aim to integrate
      psychotherapeutic intervention in order to lessen emotional impairment, to change
      behavioral patterns (which advocate rest and the avoidance of physical activity),
      and to change cognitive attitudes and fears concerning exercise and work ability.
      Nevertheless, the interplay of cognitive measures and disability in treatment
      programs still remains an unclear issue. METHODS: Ninety disabled patients with
      chronic low back pain were admitted to an 8-week outpatient program of functional
      restoration and behavioral support. The program consisted of a pre-program
      (education, stretching and calisthenic exercises) and an intensive treatment
      period (physical exercises, back school education, cognitive behavioral group
      therapy, relaxation training, occupational therapy, vocational counseling), which
      took place for 5 weeks, 7 h a day, as an outpatient program. The targets of the
      psychological interventions were (a) to change maladaptive behavior (inactivity,
      social withdrawal) and increase the patient's activity level at home, (b) to
      alter maladaptive cognitions (somatization, catastrophizing, passive expectations
      concerning treatment) and to improve their own positive coping skills, (c) to
      identify and stop operant conditioned behavior, and (d) to prevent depressive
      symptoms and strengthen the level of emotional control. The program's philosophy
      encouraged the patients' active efforts to improve their functional status within
      a therapeutic environment that reinforced positive behavior traits conductive to
      getting well. The main therapeutic target was to facilitate a return to work.
      Apart from a medical examination and a personal interview, the patients' physical
      impairment, pain descriptions, and psychological distress (according to different
      criteria for evaluation) were also measured. This included variables such as
      depression, psychovegetative complaints, quality of life and workplace
      satisfaction, disability, and coping with disease. Measurements were repeated at
      the end of the 8-week program, and following 6- and 12-month intervals. RESULTS:
      In comparison with the initial values, a statistically significant improvement
      became evident in reducing pain, disability, depression, and psychovegetative
      signs (P < 0.001). Nearly all results remained stable at the 6- and 12-months
      examinations. Apart from these results, coping measurements demonstrated little
      improvement in the three factorial coping dimensions. By use of regression
      analyses, a differentiated description of psychosocial connections became
      apparent in three different ways of coping (catastrophizing, searching for
      information, cognitive control) and parameters of disability. Disability levels
      corresponded poorly with pain descriptions, physical impairment and coping
      dimensions. This result indicates that disability should be viewed as a separate
      component in assessing the patients' description of low back pain. CONCLUSION: An
      analysis of coping dimensions demonstrated that current cognitive measures might
      be too general to explain low back disability adequately. In addition, the
      results indicate that the use of the 'catastrophizing' factor as a separate
      variable is questionable, since it may simply be a symptom of depression. The
      relevance of coping as a sensitive parameter for change is also addressed. It is
      suggested that an alteration in coping strategies may be an important treatment
      effect, but is subject to individual prerequisites to maximize treatment
      response. Thus, future research must focus on the complex interactions between
      personality variables, environmental factors, and the coping demands posed by the
      specific nature of pain problems. A more lengthy evaluation of so-called 'fear
      avoidance beliefs' in combination with 'disability' and coping dimensions could
      possibly lead to further treatment on the development of chronicity in chronic
      low back pain patients.

PMID- 12799845
TI  - [The clinical use of spinal opioids, part 2].
AB  - The most significant non-systemic side effects of spinal opioids are pruritus,
      urinary retention and delayed respiratory depression. Pruritus can occur after
      any opioid, but its incidence may differ with the affinity of the particular
      opioid to the opioid receptor. Spinal opioid receptors seem to influence urinary
      retention due to urodynamic effects. Urinary retention can be antagonized by
      naloxone; however, large doses will also antagonize the analgesic effects.
      Delayed respiratory depression after spinal opioids is a very rare, but
      significant complication. In general, respiratory depression after spinal
      lipophilic opioids will occur earlier than morphine, however the incidence is
      probably similar. There is some evidence to suggest that the risk of respiratory
      depression is similar regardless of the route of administration (intramuscular,
      intravenous, spinal, PCA). Sound knowledge among physicians and nurses, adequate
      treatment plans, and individual patient selection are essential to avoid
      significant complications of spinal opioids. If these requirements are fulfilled,
      most patients can be safely treated with spinal opioids even outside the
      intensive care unit.

PMID- 12799846
TI  - [Multidisciplinary treatment program for chronic low back pain, part 2. Somatic
      aspects].
AB  - PROBLEM: There is a great need to expand current knowledge of the various
      functional capacity measurements used in the rehabilitation of chronic low back
      pain (CLBP) patients. The literature on these patients reports that mobility,
      endurance, trunk strength and lifting capacity decrease during the process of
      chronicity. Chronically disabled patients appear to have lower functional
      capacity than asymptomatic persons. METHODS: Our study group consisted of 90
      disabled CLBP patients (44 female, 46 male; average age 42 years) who underwent a
      multidisciplinary 8-week daily treatment program of functional restoration with
      behavioral support (instruction, endurance training, strength exercises,
      behavioral and treatment to facilitate return to work therapy). Initially these
      patients where compared with 107 asymptomatic persons (44 female, 63 male,
      average age 41 years). The patients were investigated before and after treatment,
      and at intervals of 6 and 12 months. The reliability of the functional
      measurements was evaluated by interrater comparison. Physical assessment included
      a medical examination (mainly diagnosis of radicular or nonradicular pain),
      changes in the lumbar spine revealed by X-ray studies according to Herron and
      Turner, rating of physical impairment according to Waddell, flexibility, length
      of hamstrings muscles (SLR), test of power and endurance of trunk movement by
      standardized exercises according to the Swiss group of Spring and isokinetic
      measurements (LIDO Back), tests of lifting capacity (LIDO Lift), and (in part) of
      general endurance on a cycle ergometer (CASE 15 Marquette). RESULTS: Physical
      findings showed that mobility was reduced substantially in patients suffering
      from back pain due to reduced SLR (shortened hamstrings) and decreased spinal
      mobility. Patients also demonstrated significant reductions in their ability to
      perform lifting tasks in comparison to healthy individuals. The results of trunk
      flexion showed no significant differences between patients and the control group,
      whereas the ability to perform trunk extension was much better in the control
      group. In principle we found the same results with isokinetic measurements as in
      the exercises without machines. Cardiovascular endurance was also much better in
      the control group than it was in the back pain patients. At the end of the
      treatment program all physical deficits were improved significantly. In many
      cases performance was comparable with that of the control group. With time,
      however, training effects gradually decreased. The success of treatment (return
      to work, absence from work, pain reduction, use of medical care) was independent
      of the functional status of the patients before and after treatment. CONCLUSION:
      Study results showed that physical capacity in disabled patients with low back
      pain is substantially reduced in comparison to persons who do not suffer from
      back pain. The only exception was in trunk flexor strength and endurance, in
      which measurements did not differ between the patients and the control group.
      However, even CLBP- patients with long-term pain and severe physical illness can
      successfully improve their physical condition by participating in an active
      treatment program. Back extensor muscle training has to be included in physical
      therapy. Because of loss of condition during the time after treatment, regular
      monitoring of patients and their home training programs is necessary. Overall,
      treatment of CLBP has to include physical training and psychosocial treatment to
      achieve satisfactory results.

PMID- 12799848
TI  - [Substance P, somatostatin and monoaminergic transmitters in the cerebrospinal
      fluid of patients with chronic idiopathic trigeminal neuralgia].
AB  - The etiology of trigeminal neuralgia is unknown, but both peripheral and central
      causes have been suggested. To investigate the role of central neurochemical
      mechanisms we measured epinephrine, norepinephrine and their breakdown product,
      vanilly mandelic acid (VMA), in the cerebrospinal fluid (CSF) of 16 patients
      (53.3 +/- 8.3 years) suffering from trigeminal neuralgia. As markers for the
      dopaminergic system, we determined CSF levels of dopamine and its metabolite
      homovanillic acid (HVA). As a marker for the serotonergic system, we measured CSF
      levels of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). In addition,
      levels of the neuropeptides substance P and somatostatin were determined. The
      concentration of norepinephrine (P < 0.01), VMA (P < 0.05) and HVA (P < 0.05)
      were significantly decreased in patients with trigeminal neuralgia and correlated
      with the duration of the disease and depression scores. 5-HIAA was also
      significantly decreased (P < 0.05) compared to control patients. Whereas
      substance P was significantly elevated (P < 0.05), somatostatin was significantly
      decreased (P < 0.05). Various correlations between the classical
      neurotransmitters and the neuropeptides could be established. We hypothesize than
      the sum of complex neurochemical changes plays a role in the etiology of
      trigeminal neuralgia, which can be separated in local and more central
      proceedings. The increase in substance P, a major nociceptive neuromodulator,
      supports the concept of a local neurogenic inflammation, possibly located in the
      trigeminovascular system. Depending on the duration of the disease and
      depression, the loss of serotonergic, dopaminergic and noradrenergic innervation
      seems to reflect more central changes, possibly due to alterations in their
      antinociceptive descending pathways.

PMID- 12799847
TI  - [Constipation after tilidine/naloxone and tramadol in comparison to codeine. A
      dose response study in human volunteers].
AB  - Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic,
      has been supposed to have little effect on propulsive gastrointestinal motility.
      However, this has not been specifically studied in man. Following institutional
      approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone,
      and codeine, respectively, in a double-blind randomised cross-over design.
      Additionally, 12 further volunteers were given 100 mg of each opioid in a double
      blind, randomised fashion, followed by measurement of gastrocoecal transit time.
      Gastrointestinal transit time was measured using the lactulose H(2)-breath test.
      A threefold increase in end-expiratory hydrogen when compared to the control
      value was considered the end point of gastrocoecal transit. At the low dose (50
      mg) the three opioids did not differ significantly with regard to their effect on
      gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min
      for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7
      SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in
      mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/
      12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The
      increase in gastrocoecal transit time was significant (P < 0.01) for high doses
      of tilidine/naloxone and codeine in contrast to the effect of the low doses. This
      lesser constipation effect may be due to the reduced affinity of tramadol to the
      mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P
      < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo
      was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of
      tilidine/naloxone and codeine than after tramadol. Perspiration was significantly
      higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and
      codeine. Sedation is considered a typical symptom of analgesics interacting with
      centrally located opioid receptor sites. The higher incidence of perspiration
      after tramadol suggests that monominergic pathways may be involved in
      thermoregulation. In conclusion, the opioids tilidine/naloxone and codeine at the
      doses used significantly prolong gastrointestinal transit time in the high-dose
      range. Since tramadol does not induce a dose-related increase in gastrocoecal
      transit time, it may be a useful analgesic in patients who are prone to
      developing constipation during high-dose opioid therapy.

PMID- 12799849
TI  - [Special features of orthopaedic pain treatment in diseases of the spine].
AB  - Besides the treatment of postoperative pain, working together with the
      anaesthesiologist, orthopaedic doctors are mostly involved in diseases of the
      locomotor system where pain is a leading feature. Painful orthopaedic diseases
      are very frequent. They afford a special diagnostic procedure. The pain treatment
      consists of special orthopaedic therapy and local injections with low doses of
      local anaesthetics and steroids at the site of pain. This treatment helps to
      avoid the use of high-dose systemic analgesics and perhaps avoids the need for
      operations.

PMID- 12799850
TI  - [Not Available].

PMID- 12799851
TI  - [Between symbol and symptom: pain and its meanings in classical antiquity].
AB  - According to semiotics, which may be defined as the doctrine of the essential
      nature and fundamental varieties of signs, objects, and interpretants, pain is
      considered to be a sign (significant) with very different meanings (significance)
      either as a naturalistic symptom (of disease) or as a symbol used in a
      metaphorical context. When following this methodological perspective it is
      possible to interpret medical as well as poetic writings on equal terms. In
      Graeco-Roman medical texts pain was mostly understood as a result and an
      indicator of disease, but nonetheless as a symptom which seemed to be actively
      produced by the affected body. Especially in the Corpus Hippocraticum dating from
      the 5th and 4th century B. C. this materialistic and at the same time
      psychosomatic attitude can be noticed. Aristotle (4th century B. C.), Celsus (1st
      century A. D.), and the famous experimental physiologist Galen (2nd century A.
      D.) agreed that pain was a sign of evil which should be fought without exception.
      It was Galen who added the disturbance of function (functio laesa) as the fifth
      cardinal sign of inflammation to the four well-known cardinal signs of Celsus
      (rubor, calor, tumor, dolor). He also coined the term [see text] to characterize
      an attack of migraine. In algotherapy, Galen used a complex pharmacological
      system which was based upon the four cardinal qualities of humoral pathology. On
      the other hand, pain was designed as a multi-dimensional symbol by the famous
      Graeco-Roman epic poets. In Homer's Odyssey (8th century B. C.), pain appears
      transformed into the shape of a scar which is visible and palpable on the hero's
      leg like an identification tag, whereas in Virgil's Aeneids (1st century B. C.)
      pain symbolizes weakness and defencelessness which can only be alleviated by the
      goddess Venus.

PMID- 12799855
TI  - [Not Available].

PMID- 12799854
TI  - [Radiographic clinical and functional diagnosis and treatment of low back pain
      associated with pelvic malposition].
AB  - Low back pain ist frequently associated with malposition of the pelvis due to an
      imbalance of the postural muscles. In these patients functional malposition of
      both the sacrum and the ileum can be observed, resulting in differences in the
      length of the legs. We investigated whether the return to a normal position
      correlated with pain relief. METHODS: A total of 40 control patients and 65
      patients with low back pain were included in this retrospective study. Prior to
      the start and at the end of the treatment period the differences in the length of
      the legs were determined manually and radiographically at the ankles with the
      patient in the supine and sitting position. Furthermore, somatic dysfunctions at
      C0/C1 or C2/C3 were determined in all patients. In the low back pain group, 39
      patients were treated with manual therapy at the cervico-occipital joints and/or
      infiltration of the iliosacral joint with local anaesthetics and 26 patients were
      treated with parenteral non-steroidal anti-inflammatory drugs (NSAIDs). The
      success of the treatment was determined after 6 months and correlated with a
      return to the normal pelvic position. RESULTS: Somatic dysfunction at C0/C1 or
      C2/C3 and differences in the length of the legs were observed in 32 control
      patients and in all patients with low back pain. Manual therapy/lidocaine
      infiltration resulted in complete long-term pain relief in 23 patients (59 %),
      while in the NSAID group only 4 patients (15 %) became pain free (P < 0.05). Long
      term pain relief significantly correlated with normalization of the pelvic
      position. CONCLUSION: Differences in the length of the legs can be successfully
      treated by manual therapy at C0/C1 or C2/C3 in the majority of patients with
      pelvic malposition. However, infiltration of the iliosacral joints is often
      required as additional therapy for short-term and long-term pain relief.
      Treatment with NSAIDs alone is only seldom effective in cases of pelvic
      malposition and rarely affords long-term pain relief.

PMID- 12799853
TI  - [Multidisciplinary treatment program for chronic low back pain, part 1.
      Overview].
AB  - A multimodal treatment program is presented in cases of functional restoration
      for chronic low back pain. The study comprises four parts. Part I gives an
      overview of the different results of the study. Part II focuses on the medical
      and functional examination in comparison with persons who do not suffer from back
      pain. Part III describes psychosocial aspects (depression, complaints, ways of
      coping, disability) and psychotherapy. In part IV prognostic factors and their
      reliability for predicting treatment outcome (return to work, pain intensity,
      self-assessment of success by patients) are examined. In addition the relevant
      effects of the program on social and health care systems are also addressed.
      PROBLEM: The incidence of low back pain is continuously increasing, causing
      tremendous costs for the health insurance system. Therefore effective treatment
      methods are needed that take into account somatic, psychological and social
      factors. Chronic low back pain is conceptualized as a complex phenomenon
      including biological, social and psychological aspects, all of which should be
      addressed in a treatment program. A multimodal treatment program for chronic low
      back pain is presented, in which physical activity and cooperation of the patient
      are the primary targets. Therapeutic aims focus less on pain reduction and
      emphasize instead pain control, individual responsibility of the patient, and
      early reintegration into the working environment. The specific goals of the
      program are to increase the physical abilities of the patients (i. e.,
      flexibility, strength and endurance), to increase patients' knowledge and the use
      of body mechanics and back protection techniques, to decrease medication-intake,
      to decrease dependency on the medical community, to improve patients' own
      positive coping skills and levels of emotional control, to increase the patient's
      activity level at home and to facilitate a return to work. METHODS: A total of 90
      disabled patients with chronic low back pain were admitted to an 8-week program
      of functional restoration and behavioral support. The program consisted of a pre
      program (3 weeks: education, stretching and calisthenic exercises) and an
      intensive treatment period (aerobics, functional strength and endurance
      exercises, back exercises, cognitive behavioral group therapy, relaxation
      training, socioeconomic and vocational counseling) which took place for 5 weeks,
      7 h a day, on an outpatient basis. Apart from a medical examination and a
      personal interview, the patients' physical impairment, pain descriptions, and
      psychological distress (according to different criteria for evaluation) were also
      measured. This includes variables such as depression, psychovegetative
      complaints, quality of life and workplace satisfaction, disability, and coping
      with disease. Measurements were repeated at the end of the 8-week program, and
      after 6 and 12 months. RESULTS: In total 84 patients (94 %) were examined
      following treatment. There was a statistically significant improvement in
      flexibility, strength, lifting capacity, and endurance measurements ( p < 0.001)
      at the end of the treatment. In addition, significant reductions in pain,
      disability, depression, and psychovegetative signs were demonstrated ( p <
      0.001). There was a decreased use of medical treatment for back pain following
      the program, with 42 % of the patients refraining from the intake of analgesics,
      followed by a significant reduction in physiotherapy and the consultation of
      physicians. Assessment of the patients' reported increased activity levels at
      home also supported findings that statistical improvements were significant.
      Sixty-three percent of the patients were found to have returned to active,
      productive work following discharge from the program. Most of the improvements
      remained stable at the 6- and 12-month follow-up examinations. CONCLUSION: The
      results demonstrate the effectiveness of the multimodal program of functional
      restoration, not only concerning positive changes in somatic, psychological and
      physical variables, but also with respect to the number of patients who returned
      to work. Our methods are also compared with the discrepant results of multimodal
      treatment in the United States and Scandinavia.

PMID- 12799852
TI  - [The clinical use of spinal opioids, part 1].
AB  - Spinal opioids are effective analgesics for surgical and non-surgical pain.
      Central and systemic side effects are less frequent than with epidural local
      anaesthetics or parenteral opioids. This review focuses on the analgesic efficacy
      of spinal opioids and their combination with local anaesthetics for postoperative
      analgesia, including patient-controlled epidural analgesia. Intrathecal
      administration of opioids has some advantages over their administration by the
      epidural route. Several factors may influence selection of the opioid; however,
      in most situations morphine is the drug of choice. Thoracic epidural
      administration of opioids seems to have no clinically important advantages over
      the lumbar route in terms of quality of analgesia, adverse effects, doses
      required or pulmonary function. However, evidence suggesting that effective
      postoperative analgesia can significantly improve postoperative morbidity in
      patients at risk is accumulating. In such patients, combined use of epidural
      local anaesthetics and opioids may become the technique of choice for
      postoperative analgesia. However, there is no evidence that this would have any
      clinically relevant benefit in low-risk patients.

PMID- 12799856
TI  - [Animal models and their results in relation to the therapy of migraine].
AB  - Until now, our understanding of migraine pathophysiology has been fairly
      incomplete. So far no animal model has allowed an explanation of all facets of
      the clinically heterogeneous condition migraine. However, it is now generally
      accepted that the migraine headache is due to activation of the trigeminal
      system. The model of neurogenic inflammation after stimulation of the trigeminal
      ganglion or systemic administration of capsaicin allows study of the inhibitory
      interactions between antimigraine compounds and peripheral trigeminal fibre
      terminals that sustain a sterile meningeal inflammation through release of
      allogenic and vasoactive neuropeptides, such as substance P and calcitonin gene
      related peptide. Studies with the model of superior sagittal sinus stimulation
      have revealed central actions of antimigraine agents such as ergotamine and
      sumatriptan, but also acetylsalicylic acid on neurotransmission of trigeminal
      nociceptive input in the brainstem. A likely explanation for the slowly
      progressing neurological deficits is cortical spreading depression (CSD), which
      can easily be elicited in many species. However, CSD has not been observed in
      vivo in humans. The described models strongly influenced the development of new
      medications for migraine treatment and have improved our understanding of
      migraine pathophysiology.

PMID- 12799857
TI  - [Exteroceptive suppression of activity of the temporal muscle in analysis of pain
      mechanisms].
AB  - Stimulating afferent fibers of the trigeminal nerve usually causes two successive
      suppressions (ES1 and ES2) of the voluntary muscle activity of chewing muscles.
      The first phase of decreased voluntary activity is called the early exteroceptive
      suppression period (ES1); the second phase is called the late exteroceptive
      suppression period (ES2). Between these two suppression periods is a phase of
      increased muscle activity, the so-called facilitation period (FP). Usually, in
      healthy subjects this normal pattern of exteroceptive suppression can be elicited
      regularly. The reflex answer may occur at low non-painful stimulus intensities;
      however, typically it appears to be most pronounced with high-intensity stimuli.
      Because of the obvious relationship between stimulus intensity, pain perception
      and reflex answer, the reflex is regarded as an antinociceptive reaction. Chronic
      pain syndromes like chronic tension-type headache and migraine without aura cause
      changes within the normal ES recording pattern. Furthermore, some substances used
      in pain therapy such as serotoninagonists or antagonists, acetylsalicylic acid or
      naloxon may also alter the general appearance of the ES. In this review different
      parameters that influence the ES reflex answer are summarized. Above, the
      diagnostic value of the changes of the ES for pathophysiological procedures
      regarding pain perception and pain processing in certain pain diseases is
      discussed.

PMID- 12799858
TI  - [Electrophysiological studies on headache: the contingent negative variation].
AB  - The contingent negative variation (CNV) is a slow cortical potential recorded
      from the scalp. This method allows the pathophysiology of chronic headaches to be
      elucidated. When assessed during the pain-free interval patients suffering from
      migraine without aura show significantly more negative amplitudes than healthy
      controls. This negativity reflects the activity of cerebral noradrenergic
      systems. Some studies using repeated recordings of the CNV show a periodicity in
      amplitude change. When migraine patients are assessed a few days before a
      migraine attack occurs, they show pronounced negativity, which normalized during
      the attack. Despite these interesting findings that are based on group
      comparisons, evaluating the CNV on an individual basis does not allow specific
      conclusions. Thus, assessment of the CNV is an important tool to examine
      pathophysiological aspects of chronic headaches, but is not suitable as a
      diagnostic procedure.

PMID- 12799859
TI  - [Usefulness of electrophysiology and neuroimaging in the evaluation of headache].
AB  - First time experienced severe headache combined with fever or meningism requires
      immediate evaluation by computer tomography (CT) to exclude subarachnoidal or
      cerebral hemorrhage, hydrocephalus or a tumor. If CT is normal,lumbar puncture
      must be performed to exclude meningitis and meningoencephalitis. Chronic or
      chronic recurrent headache without focal neurological deficits does not require
      EEG or CT. CT must be performed if the headache characteristics change or if the
      headache is combined with neurological deficits.

PMID- 12799860
TI  - [PET and Doppler sonography in headaches].
AB  - Whether the primary mechanisms of migraine are vascular or neurogenic is, as yet
      unresolved. Early studies using Doppler sonography prompted heterogeneous
      results, mainly due to methodological differences. However, blood flow
      measurements using single photon emission tomography (SPECT) or positron emission
      tomography (PET) have not revealed any differences in cerebral blood flow in
      migraine without aura. Moreover, specific migraine compounds do not alter
      cortical blood flow. During attacks, increased blood flow is found in the
      cerebral hemispheres in cingulate, auditory and visual association cortices and
      the brain stem. Altogether, these findings suggest that the pathogenesis of
      migraine is related to an imbalance in activity between brain stem nuclei
      regulating antinociception and vascular control, rather than in primary vessel
      diameter changes.

PMID- 12799861
TI  - [Medical therapy for menstrual migraine].
AB  - A menstrual migraine occurs in approximately 7-10 % of women suffering from
      migraine. The migraine occurs from 2 days before until 3 days after the end of
      the menstrual period. The choice of treatment depends on the duration of the
      attack, which ranges from 3 to 7 days. An attack of up to 3 days duration should
      be treated with acetylsalicylic acid, ergotamine tartrate or naproxen, each in
      combination with an antiemetic (domperidone, metoclopramide). If there is no
      response, sumatriptan can be administered orally (25-100 mg) or subcutaneously (6
      mg). In the attacks continue for more than 3 days, short-term prophylaxis with
      naproxen or the application of an estrogen-containing patch is indicated. Neither
      ovulation inhibitors nor traditional migraine prophylaxis has an influence on
      menstrual migraine. Patients should keep a headache diary. Short-term prophylaxis
      with ergotamine tartrate or tamoxifen is obsolete.

PMID- 12799863
TI  - [Homeopathy in headaches. A review].
AB  - Homeopathy as an alternative to conventional therapy is becoming increasingly
      popular. Although interest is rising, little is known about the real
      effectiveness of homeopathic therapy in headaches. Three studies addressing this
      question are discussed: an Italian migraine study, the London migraine study and
      our own, the Munich headache trial. While the first one reported very high
      effects, the best ones known in the literature, the results of the other two
      trials do not endorse this first finding. The London trial did not show any
      effect other than placebo, although a different time trend was reported. The
      Munich study failed to show any difference between homeopathy and placebo
      whatsoever. The merits and shortcomings of these studies are discussed. At
      present, we do not have any evidence that homeopathic therapy has any effect
      other than a placebo effect. However, this can be very impressive sometimes. We
      do not know which variables are correlated with placebo effectiveness, and we do
      not have any data on real-type homeopathy outside a trial setting, as there are
      no data available.

PMID- 12799862
TI  - [Acupuncture in headache therapy].
AB  - Acupuncture is now being increasingly used in the treatment of headache.
      Acupuncture is a technique originating in Asia, from countries that have a
      cultural background with a fundamentally different concept of disease and
      therapy. Up to now, sustained application of acupuncture in Western medicine has
      been impeded by the lack of a scientifically convincing explanation of the
      mechanisms of action in terms of neurobiological criteria. Acupuncture is being
      used empirically in the treatment of migraine; clinical studies have been
      published. A definitive evaluation of acupuncture based on well-founded clinical
      experimental studies has yet to be made. The investigation was carried out in
      migraine patients who were divided into two subgroups in a control group design
      with two different stimulation techniques. The verum group was treated with the
      correct point location, normal prick depth and elicitation of a needle sensation.
      The control group received treatment at points that are far away from the
      acupuncture points, using a superficial prick technique and without eliciting a
      needle sensation. The effect of therapy was appraised by means of headache
      diaries with subsequent interference statistical and individual case analysis. In
      the present study comprising 81 patients, the incidence of the attacks was
      significantly reduced in both subgroups. The effect of acupuncture treatment was
      of comparable magnitude to that of the beta-blocker metoprolol. The advantage of
      acupuncture treatment consists in the lack of side effects such as
      gastrointestinal symptoms or an increase in weight. A minor side effect was only
      reported in one case. In the data analysis with the interference statistical
      method, verum acupuncture was superior to the control in only one subgroup. The
      possibility that the addition of further points (distant points) can explain this
      effect on the basis of the hypothesis of a central modulation of the migraine
      process is discussed. Acupuncture shows a sufficiently pronounced and sustained
      therapeutic effect for its use to be considered in a possible interval treatment
      of migraine.

PMID- 12799864
TI  - [Epidural and intrathecal administration of alpha 2-adreno-ceptor agonists for
      postoperative pain relief].
AB  - Spinal clonidine interacts with pre- and postsynaptic alpha(2)-adrenoceptors on
      afferent neurons in the superficial dorsal horn of the spinal cord: it causes
      analgesia by inhibition of the synaptic and electrotonic neurotransmission of
      nociceptive impulses. Epidural doses higher than 4 microg/kg have an analgesic
      onset time of less than 30 min, reduce pain by more than 70 %; these effects last
      for 4-5 h. Epidural clonidine analgesia is accompanied by a reduction in heart
      rate, cardiac output and blood pressure of approximately 20 % compared with
      baseline. The haemodynamic side effects mean close supervision is needed during
      the first hour after epidural application and limit the use of epidural clonidine
      to patients who are refractory to the analgesic effects of epidural opioid or
      local anaesthetics. In these patients excellent results can be achieved either
      with clonidine alone or with a combination of clonidine and an opioid or a local
      anaesthetic to exploit the additive or supra-additive interactions of these
      drugs.

PMID- 12799866
TI  - [Depressivity and successful outcome of spinal surgery].
AB  - INTRODUCTION: The relationship between depression and the outcome of low back
      surgery was investigated. Data analysis was based on two assumptions: (1)
      Presurgical assessments of depression are correlated with the outcome of surgery,
      and, therefore, depression can be interpreted as a risk factor for surgical
      failure. (2) Postsurgical assessments of depression are correlated with the
      outcome of surgery, and therefore, depression can be interpreted as a response to
      treatment failure. METHODS: The sample was made up of 78 patients who had
      undergone lumbar nucleotomy and 132 patients with lumbar spondylodesis. Treatment
      outcome was evaluated 6 months after surgery in the nucleotomy group and 9 months
      after surgery in the spondylodesis group. Depression was assessed with the Beck
      Depression Inventory (BDI). Measures of treatment outcome were an objective
      rating system for the surgical result, functional impairment, return to work,
      subjective estimations of the patient, and pain intensity. RESULTS: Presurgical
      depression scores showed no significant relationship with surgical outcome in
      nucleotomy patients. In spondylodesis patients, however, there was a significant
      negative correlation with the patients' subjective outcome ratings. Postsurgical
      depression scores, on the other hand, were significantly related to almost all of
      the outcome variables in both treatment groups. Patients with clinically relevant
      postsurgical depression scores were significantly more likely not to benefit
      sufficiently from surgery than those with clinically not relevant depression
      scores. DISCUSSION: Our findings favour assumption 2 over assumption. 1. In the
      light of our findings, depressiveness is interpreted as a response to a non
      beneficial outcome of surgery. The need for an interdisciplinary approach
      combining psychological counseling or treatment and physical therapy for those
      patients who do not benefit from surgery is discussed.

PMID- 12799867
TI  - [Differentiation of pain-related and morphine related impairment of cognitive
      performance and mood in bone marrow transplantation patients].
AB  - AIMS: Severe pain of mucositis induced by cytostatic conditioning therapy in bone
      marrow transplantation (BMT) patients generally requires continuous parenteral
      opioid treatment. Cognitive and psychological disturbances are frequent
      complications subsequent to BMT and may result from cerebral opioid side effects.
      The aim of the study was to evaluate the efficiency of continuous morphine in
      mucositis pain and the side-effects in BMT patients. Particular emphasis was
      placed on the question of whether reaction times, which are usually measured to
      estimate opioid effects upon vigilance, are influenced by pain-induced cognitive
      impairments in pain patients. METHODS: While in hospital, 10 BMT patients were
      examined daily with the aid of a mucositis scale, subjective visual analog scales
      (VAS) for pain and mood parameters, a German version of the McGill pain
      questionnaire (MPQ), and a mental performance task battery, and the morphine
      given was documented. Mental performance tests were simple auditory reaction time
      and choice reaction time. Seven patients also performed a Sternberg memory search
      test in which they had to use 'yes' and 'no' response keys to match visually
      presented test letters to a previously memorized set of letters. Practice and
      baseline data were collected within the first week before BMT. RESULTS: The
      intensity and duration of mucositis differed from patient to patient, resulting
      in different pain intensities and MPQ scores. Prolongation of the choice reaction
      time averaged over the period of mucositis treatment correlated significantly
      with residual pain intensity (Spearman r(s) = 0.88, p < 0.01) but not with
      morphine dose (r(s) = 0.35, p = 0.33). For the Sternberg memory search test
      greater correlation coefficients resulted between reaction time and morphine dose
      (r(s) = 0.86, p = 0.014) than between reaction time and residual pain intensity
      (r(s) = 0.61, p = 0.15). In turn, pain intensity, unlike morphine dose, was
      significantly correlated with high scores in the mood parameters for depression,
      passivity, and tiredness. CONCLUSIONS: It is concluded that both pain and
      morphine can impair cognitive performance, but that these mental stressors seem
      to differ according to qualitative criteria. Whereas pain might slow reaction
      time by distracting a patient's attention, particularly in low mental demand
      tasks, morphine could interfere with more specific cognitive processes, such as
      short-term memory operations, that are required in more complex tasks.

PMID- 12799865
TI  - [Alpha 2-adrenoceptor agonists for the treatment of chronic pain].
AB  - The antinociceptive effect of alpha(2)-adrenoceptor agonists is mediated by
      activation of descending inhibiting noradrenergic systems, which modulates 'wide
      dynamic-range' neurones. Furthermore, they inhibit the liberation of substance P
      and endorphines and activate serotoninergic neurones. Despite this variety of
      antinociceptive actions, there is still little experience with alpha(2)
      adrenoceptor agonists as therapeutic agents for use in chronic pain syndromes.
      Studies in animals and patients have shown that the transdermal, epidural and
      intravenous administration of the alpha(2)-adrenoceptor agonist clonidine reduces
      pain intensity in neuropathic pain syndromes for periods varying from some hours
      up to 1 month. Patients suffering from lancinating or sharp pain respond best to
      this therapy. Topically applied clonidine (200-300 microg) relieves hyperalgesia
      in sympathetically maintained pain. Epidural administration of 300 microg
      clonidine dissolved in 5 ml NaCl 0.9 % has also been shown to be effective. In
      patients suffering from cancer pain tolerant to opioids, pain control has proved
      possible again with combinations of opioids and clonidine. In isolated cases
      clonidine has been administered epidurally at a dose of 1500 microg/day for
      almost 5 months without evidence for any histotoxic property of clonidine. Side
      effects often observed during administration of alpha(2)-adrenoceptor agonists
      are dry mouth, sedation, hypotension and bradycardia. Therapeutic interventions
      are usually not required.

PMID- 12799868
TI  - [Psychological research on pain in Western Europe].
AB  - Utilizing MEDLINE and PSYCLIT, a search for articles covering psychological
      research on pain in the Western European countries was undertaken for the period
      from 1 January 1990 to 31 December 1994. A total of 398 publications were
      identified, of which 44 were classified as experimental research in the
      laboratory, 33 as psychodiagnostic and 225 as clinical studies. The most frequent
      diagnosis was back pain, followed by musculoskeletal pain and headache. With
      regard to the total number of publications, Germany was first, followed by The
      Netherlands and Great Britain. In an analysis of the subcategories, the leading
      position of Germany could only be confirmed with respect to laboratory studies;
      in psychodiagnostic publications, Germany fell back behind Great Britain and The
      Netherlands. In clinical studies, Germany was second to Sweden. Relating the
      number of publications to the number of personnel estimated to be engaged in
      research, The Netherlands and the Scandinavian countries demonstrate very high
      efficiency. Compared with Germany, these countries facilitate the integration of
      psychological procedures into an interdisciplinary management of pain.

PMID- 12799870
TI  - [Not Available].

PMID- 12799869
TI  - [The sympathetic skin response--a useful method for the diagnosis of reflex
      sympathetic dystrophy?].
AB  - The aim of the present study was to examine the value of the sympathetic skin
      response (SSR) in the diagnosis of reflex sympathetic dystrophy (RSD). PATIENTS
      AND METHODS: SSR was recorded in 20 normal subjects and in 24 patients with
      predominantly chronic RSD. In 3 patients with RSD, additional recordings of the
      SSR were performed before and several times after administration of local
      anaesthetics via a plexus catheter on the diseased side. SSR was recorded with
      standard EMG apparatus. Disc electrodes were positioned on the middle of the
      volar and dorsal surfaces of the hands and feet. Electrical stimuli were applied
      to the middle of the forehead at irregular intervals longer than 60 s. RESULTS:
      In normal subjects inter- and intraindividually different monophasic, biphasic
      and triphasic potentials without difference in the waveform between sides were
      recorded. SSR abnormalities were found in 15 patients with RSD and correlated
      with the severity of the disease. In patients with slight dystrophy SSR was
      predominantly normal, while in most of those with intermediate dystrophy
      differences in the SSR waveform between sides were observed. In the presence of
      severe dystrophy SSR amplitude was predominantly decreased on the affected side.
      Following the administration of local anaesthetics via a plexus catheter, the
      differences in SSR waveform became smaller in patients with initial distinct side
      difference of the waveform. However, differences in SSR amplitudes or latencies
      between sides were not affected. CONCLUSIONS: Side differences in SSR waveform
      could be due to a mild, reversible unilateral sudomotor dysfunction, whereas
      differences in SSR amplitude or latency indicate more serious damage to sudomotor
      activity, possibly due to dysfunction of autonomic fibres. In patients with
      slight dystrophy sweat secretion is predominantly normal, while in severe
      dystrophy more serious damage to the sweat secretory system can be observed. SSR
      provides useful information on sudomotor dysfunction in patients with RSD.
      However, as there is no consensus on the clinical criteria for diagnosis of RSD,
      it is also not possible to determine the diagnostic value of SSR in the diagnosis
      of RSD.

PMID- 12799871
TI  - [Special features of acute pain in the paediatric age group].
AB  - Treatment of acute pain in children is a very important part of every doctor's
      work, and requires well-founded knowledge of this particular age group. Even in
      preterm infants pain apperception is fully developed, so that adequate analgesia
      is necessary. During infancy and childhood the individual developmental stage
      must be taken into account; the ability to cope with pain often differs
      distinctly from that in adults. At the starting of an analgesic regimen
      nonsteroidal analgesics are sufficient in most cases. If pain is severe iv
      morphine should be used much more often in children, because it is very effective
      and side effects can be avoided. In contrast to chronic pain management, pain
      dependent analgesic management can be considered as beneficial. Good knowledge of
      a small number of drugs with their pharmacological profile is sufficient for
      effective analgesic results even in severe pain states in children. Behavioural
      medicine should be integrated into paediatric pain management as soon as
      possible. An early start of pain reduction and prophylaxis is the best basis for
      development in the direction of competent pain coping behaviour in adult life.

PMID- 12799872
TI  - [Experimental data on the interactions of alpha 2-adrenoceptor agonists with
      anaesthetics, analgesics and local anaesthetics].
AB  - The interactions of alpha(2)-adrenoceptor agonists with anaesthetics, analgesics
      and local anaesthetics are not only of practical importance in many areas of
      anaesthesia and pain therapy, but also of significant theoretical interest.
      Laboratory investigations and animal research allow us to study the
      pharmacological mechanisms of these drug interactions by using the tools of
      molecular biology. This may lead to the establishment of a scientific basis
      allowing the definition of rational drug therapies. In the first part of this
      overview, recent data on local anaesthetic effects of alpha(2)-adrenoceptor
      agonists on peripheral nerve conduction and their interaction with local
      anaesthetics are presented. Some important experimental work focusing on additive
      and synergistic spinal interactions of alpha(2)-adrenoceptor agonists with
      opioids and some other agents are then discussed. Finally, there is a brief
      reference to the central role of the spinal cord in mediating and controlling
      nociception.

PMID- 12799873
TI  - [Spinal administration of alpha 2-adrenoceptor agonists and opioids or local
      anaesthetic agents].
AB  - The effects of combined spinal administration of alpha(2)-adrenoceptor agonists,
      local anaesthetics, and opioids have been extensively studied. The motor and the
      sensory block of spinal and epidural anaesthesia is enhanced and prolonged by the
      combination of clonidine with the local anaesthetics lidocaine, tetracaine and
      bupivacaine. Because higher plasma levels of local anaesthetics were measured
      when clonidine was injected epidurally, the enhancement of the local
      anaesthetic's effect by clonidine is not due to slowed resorption, but rather to
      direct spinal and supraspinal effects of clonidine. Furthermore, direct local
      anaesthetic properties of clonidine on nerve fibres are discussed. In addition,
      in children the combination of clonidine and bupivacaine for caudal anaesthesia
      resulted in a marked prolongation of postoperative pain relief. Circulatory
      effects of combined clonidine and local anaesthetics are the result of the
      specific spinal blockade and the central and peripheral effects of clonidine. The
      combined epidural and intrathecal administration of opioids and alpha(2)
      adrenoceptor agonists provides better postoperative pain relief than the
      administration of either substance alone. In humans, the interaction seems to be
      additive rather than supra-additive. Because of its limited duration of action,
      continuous administration of clonidine is recommended, especially when it is used
      in combination with opioids. Neither the incidence nor the severity of side
      effects is increased by a combined therapy with opioids. Despite the sedative
      properties of clonidine, there is no increased risk of respiratory depression
      when clonidine is given in combination with opioids. The inhibiting effect on the
      sympathetic nervous system activity regularly observed during spinal
      administration of clonidine supports the value of this therapy and will support
      its use in the future. Therefore, the combination of alpha(2)-adrenoceptor
      agonists with local anaesthetics or opioids is reasonable and may improve
      anaesthetic practice.

PMID- 12799874
TI  - [Oral papaverine prevents morphine-induced constipation without interfering with
      analgesia achieved with oral morphine].
AB  - Long-term administration of morphine for the treatment of chronic pain produces
      constipation; this requires the use of laxatives, which impair water absorption
      and upset the electrolyte balance. Morphine-induced constipation is mainly due to
      inhibition of the propulsive movement of the gastrointestinal tract combined with
      spastic contraction of smooth circular muscles as a result of drug binding to
      opioid receptors in the tract. Since papaverine lacks affinity for opioid
      receptors but relaxes smooth muscle, it seemed possible that oral papaverine
      might be capable of diminishing constipation without impairing the analgesia
      achieved with morphine. For this purpose, experiments were carried out on rats:
      constipation was checked for by measuring the intestinal transit time, and
      analgesia was assessed by measuring the latency of the tail-flick response to
      radiant heat or nociceptive activity in single neurons of the thalamus evoked by
      supramaximal electrical stimulation of afferent C fibres in the sural nerve.
      Morphine and papaverine were administered by the oral route. Control animals
      received saline. To measure the intestinal transit time, India ink solution was
      given orally. Morphine (2.5 and 5 mg/kg orally) prolonged the transit time from
      approx. 420 min in the controls to more than 600 min, a dose of 2.5 mg/kg
      producing the maximum effect. Papaverine (0.5, 1, and 2 mg/kg) administered
      orally together with morphine significantly reduced morphine-induced constipation
      (Tables 1, 2). Papaverine given alone at a dose of 2 mg/kg caused no change in
      transit time, while 5 mg/kg significantly increased it (Table 2). The latency of
      the tail-flick response was increased by oral morphine (2.5 and 5 mg/kg) at 1, 2,
      and 3 h after administration. Papaverine (0.5, 1 and 2 mg/kg) given in
      combination with morphine left the antinociceptive effect of morphine unchanged
      (Figs. 1-3). A study of the nociceptive activity evoked in thalamus neurons of
      rats under urethane anaesthesia indicated that intestinal absorption of morphine
      was blocked. Therefore, metoclopramide (0.15 mg/kg) was injected i. v. 10 min
      before oral administration of morphine or the combination of morphine plus
      papaverine. Subsequently, morphine produced a dose-dependent depression of evoked
      nociceptive activity (Fig. 4), the mean effect amounting to 60 % of the control
      activity and being produced by 2.5 mg/kg (Fig. 5). Since in former experiments on
      nociceptive activity evoked in thalamus neurones it has been found that the
      ED(50) of i. v. morphine is 0.05 mg/kg, it is very likely that the presystemic
      elimination of orally administered morphine is very high and, in addition, that
      the efficiency of its active metabolite, morphine-6-glucuronide, is rather poor.
      When morphine 2.5 mg/kg was given together with papaverine 0.5 mg/kg, and
      morphine 5 mg/kg was administered in combination with papaverine 2 mg/kg, there
      was no significant reduction in the depressant effect of morphine on nociceptive
      activity evoked in thalamus neurons (Figs. 6, 7). The results suggest that
      papaverine given by the oral route may reduce morphine-induced constipation
      without impairment of the analgesic action of morphine in patients suffering from
      pain.

PMID- 12799875
TI  - [Forgotten pain].
AB  - A 55-year-old female patient developed a severe chronic lumbar pain syndrome over
      a period of 17 years. An intervertebral disc operation was performed 5 years
      after the start of the painful illness. The patient later developed resistance to
      therapy and was unable to stand or walk. She was confined to bed and wheelchair
      and socially completely withdrawn. Drug therapy and invasive therapeutic
      techniques escalated. An intrathecal catheter for morphine administration had to
      be removed owing to bacterial meningitis, and repeated malfunction led to several
      revisions of an epidural catheter. Withdrawal of the morphine therapy, carried
      out with the patient's agreement, was complicated by an epileptic seizure and an
      acute circulatory failure with cerebral hypoxia. The succeeding severe amnestic
      syndrome extinguished all recollection of the last 20 years, including the entire
      course of the painful illness. The patient could then be mobilised without pain.
      Consistent care avoided a relapse into the pain syndrome as the amnestic syndrome
      gradually receded. The patient was fully able to accept responsibility and not
      longer required special pain therapy. The course demonstrates that chronic pain
      disorders of a predominantly psychodynamic, and therefore corticocerebral,
      genesis are dependent on an intact memory. In such cases memory failure can
      induce pain relief.

PMID- 12799876
TI  - [Fatal outcome of a cervical nerve block].
AB  - A patient with brachialgia was admitted to a surgical clinic and a cervical nerve
      block was performed under fluoroscopic guidance. Acute severe cervical pain
      prevented completion of the procedure. On the following day the patient developed
      incomplete paralysis of both legs and arms and was transferred to a neurosurgical
      department for further diagnosis and therapy. The CT scan showed a space
      occupying cervical intraspinal haematoma, which was removed immediately as far as
      possible by a dorsal approach. Postoperatively little improvement of neurologic
      function was noticed, and 11 days after the event the patient died from a massive
      pulmonary embolism despite intense resuscitation efforts.

PMID- 12799877
TI  - [Intermittent painattacks: a typical sign of a vascular leiomyoma].
AB  - A 54-year-old women reported on intermittent attacks of pain attacks in the
      tibia, that she had for the first time during her pregnancies 24 years and 17
      years before, disappearing with the birth of her children. Nevertheless the pain
      recurred at the beginning of the climacteric and became more frequent in the
      subsequent years. The pain attacks were often triggered by a soft touch but they
      also arose spontaneously: nearly every night the patient was awakened between
      1:00 and 4:00 a. m. by a pain attack lasting about 20-40 min. Special diagnostic
      methods such as phlebography, computed tomography, scintiscan did not show any
      pathologic findings, except a residual bone deformation of the tibia as a
      consequence of a tibia fracture 20 years before. The woman was treated
      continuously for about 7 years with injections and different medical and
      paramedical methods, with no improvement. She started to write a diary about the
      times and the frequency of the pain attacks. This was diagnosed as a neurotic
      behaviour and several sessions of psychological analysis revealed many problems
      in her life. Finally, an operation was performed in the painful region, revealing
      a white elastic tumour 0.6 cm in size, which was diagnosed on histological
      examination as a vascular leiomyoma. The patient was instantly free of pain and
      still felt well 6,5 years later. According to the literature, vascular leiomyoma
      is the only tumour of the soft tissue except glomus tumour that usually produces
      severe pain attacks.

PMID- 12799878
TI  - [Quality assurance in therapy of chronic pain. Results obtained by a task force
      of the German Section of the Association for the Study of Pain on psychological
      assessment of chronic pain. IX. Multidimensional instruments for the assessment
      of aspects relating to pain and recommendations on standard procedures for
      diagnosis].
AB  - Four multidimensional inventories used as instruments for the assessment of pain
      are examined: "Fragebogen zur Erfassung der Schmerzverarbeitung' [Questionnaire
      for Assessment of Level of Coping with Pain], "Kieler Schmerzverarbeitungs
      Inventar' [Kiel Inventory of Coping with Pain], "Fragebogen zur
      Schmerzregulation' [Questionnaire on Pain Regulation], and the German version of
      the "Multidimensional Pain Inventory'. None of these questionnaires assesses all
      domains that are important in chronic pain. The recommended standardized
      assessment routine for pain centres includes the use of a diary, the rating of
      actual, average and maximum pain intensity, the application of the PDI, a measure
      of disability, and the FESV, which records cognitive processing and coping. As
      measures of general psychological dysfunction the ADS for the assessment of
      depression and the B-L, a symptom checklist, are suggested as instruments
      suitable for routine use in diagnosis and evaluation.

PMID- 12799879
TI  - Laparoscopic intragastric surgery for gastric tube cancer following
      esophagectomy.
AB  - As a result of the recent improvement of the prognosis of esophageal cancer, the
      reporting frequency of gastric tube cancer following esophageal cancer has
      increased. Gastric tube total resection following median sternotomy, a highly
      invasive surgical procedure, is applied to the cases of advanced gastric tube
      cancer, whereas endoscopic mucosal resection is selected for the cases of early
      gastric tube cancer. If endoscopic mucosal resection is not applicable for some
      reason, partial or total resection of the gastric tube following median
      sternotomy has been selected. We applied laparoscopic intragastric surgery to
      such a case: The patient, a 59-year-old man with esophageal cancer, had undergone
      subtotal esophagectomy followed by gastric tube reconstruction through the
      retrosternal route 6 years before. Since endoscopy revealed early gastric cancer
      in the body of the stomach, we tried to perform mucosal resection but failed
      because of anastomotic stenosis. However, we successfully performed intragastric
      surgery, in which a camera and forceps were inserted directly into the gastric
      tube. Thus, laparoscopic intragastric surgery is a useful technique in cases to
      which endoscopic mucosal resection is not applicable.

PMID- 12799880
TI  - Double Dieulafoy-like lesion in the stomach.
AB  - Dieulafoy's lesion is an uncommon cause of major gastrointestinal bleeding and
      may be difficult to recognize. It consists of an arteriole that protrudes through
      a tiny mucosal defect usually within 6 cm of the gastroesophageal junction on the
      lesser curve of the stomach. Despite widespread awareness of this entity, it
      remains a diagnostic challenge for gastroenterologists because of its small size
      and hidden location. Emergency endoscopy is the most effective method of
      diagnosing the disease. We report a patient, with double Dieulafoy-like lesion,
      who was successfully treated endoscopically using hemostatic clip application.
      The characteristics of the Dieulafoy's lesion, its current diagnosis, and its
      treatment are discussed.

PMID- 12799881
TI  - The impact of gastroesophageal reflux disease on quality of life.
AB  - BACKGROUND: Quality of life as a medical endpoint has become an important measure
      in clinical research. METHODS: In this article, we review the recent literature
      that has examined the impact of gastroesophageal reflux disease (GERD) and its
      treatment of quality of life. RESULTS: The increasing interest in measuring
      patients' quality of life as an outcome reflects an increasing awareness that
      traditional physiological endpoints often do not correlate well with patients'
      functional status, general well-being, and satisfaction with therapy. It has been
      shown that GERD has a significant impact on patients' quality of life; therefore,
      improvement of quality of life is one of the major goals of GERD treatment. This
      can be achieved by medical as well as surgical treatment. CONCLUSION: In addition
      to the patients' perspective, quality of life is one of the major endpoints in
      medical research that will help provide more selective treatment regimens for our
      patients.

PMID- 12799882
TI  - Comparison of intestinal transit recovery between laparoscopic and open surgery
      using a rat model.
AB  - BACKGROUND: After laparoscopic surgery (LS), patients show faster recovery of
      intestinal transit than after conventional open surgery (OS). To prove the
      mechanism of this advantage, we compared the recovery of intestinal transit using
      steel carbon balls. METHODS: Rats underwent either open laparotomy or were
      insufflated with carbon dioxide followed by the administration of steel balls
      (0.6 mm). An abdominal radiograph was taken 12 h after the operation. Compliance
      of the intestinal walls was analyzed with a computer-driven barostat device.
      RESULTS: An abdominal radiograph of 12 h after administration of the steel carbon
      balls showed the balls scattered in the small and large intestine of the LS
      patients, whereas they remained mostly in the stomach of the OS patients.
      Compliance of the intestinal walls was sustained at approximately 100 microl/mmHg
      in the LS patients, whereas it dropped to 94 microl/mmHg in the OS patients with
      the increase in balloon pressure. Histologically, the extent of serosal edema was
      more severe in the OS than in the LS patients. In terms of intestinal transit and
      irritation LS has advantage over OS. CONCLUSIONS: Intestinal transit recovery, as
      measured by the migration of steel carbon balls, is faster in LS, and gastric
      emptying is slow in OS.

PMID- 12799883
TI  - Rasmussen's model of human behavior in laparoscopy training.
AB  - AIMS: Compared to aviation, where virtual reality (VR) training has been
      standardized and simulators have proven their benefits, the objectives, needs,
      and means of VR training in minimally invasive surgery (MIS) still have to be
      established. The aim of the study presented is to introduce Rasmussen's model of
      human behavior as a practical framework for the definition of the training
      objectives, needs, and means in MIS. METHODS: Rasmussen distinguishes three
      levels of human behavior: skill-, rule-, and knowledge-based behaviour. The
      training needs of a laparoscopic novice can be determined by identifying the
      specific skill-, rule-, and knowledge-based behavior that is required for
      performing safe laparoscopy. Future objectives of VR laparoscopy trainers should
      address all three levels of behavior. RESULTS: Although most commercially
      available simulators for laparoscopy aim at training skill-based behavior,
      especially the training of knowledge-based behavior during complications in
      surgery will improve safety levels. However, the cost and complexity of a
      training means increases when the training objectives proceed from the training
      of skill-based behavior to the training of complex knowledge-based behavior.
      CONCLUSION: In aviation, human behavior models have been used successfully to
      integrate the training of skill-, rule-, and knowledge-based behavior in a full
      flight simulator. Understanding surgeon behavior is one of the first steps
      towards a future full-scale laparoscopy simulator.

PMID- 12799884
TI  - Immunologic postoperative competence after laparoscopy versus laparotomy.
AB  - BACKGROUND: Sepsis is a major complication associated with increased morbidity
      and mortality in patients treated surgically for hepatobiliary and colorectal
      diseases. Impairment of immune function after surgery may be one of the
      mechanisms causing increased susceptibility to infection. From November 1999 to
      October 2001, the perioperative and postoperative immune responses of 20 patients
      who underwent laparoscopy were compared with those of 20 patients who underwent
      laparotomy. All the patients were affected by benign pathologies. The current
      study aimed to elucidate the differences between the immune responses induced by
      the two different surgical approaches. METHODS: Immunologic function was assessed
      by a count of lymphocyte subsets (CD3, CD4, CD8, CD3-HLA-DR, CD19, CD16, CD57)
      and monocytes expressing human leukocyte antigen DR (HLA-DR). Blood samples were
      obtained 1 day before the surgical therapy, then 2 and 8 days after therapy. For
      statistical analysis, the continuous variables were compared using Student's t
      test. Probability values less than 0.05 were considered significant. RESULTS:
      With regard to T-lymphocyte function, a fall 2 days after surgery was assessed
      for both laparoscopy (p < 0.0005) and laparotomy (p < 0.00003) groups. At 8 days
      after surgery, these values had returned to the preoperative level on both
      groups. The activity of B-cells and natural killer cells was not significantly
      affected, whereas the number of monocytes expressing HLA-DR showed a long-lasting
      decrease after laparotomy (p < 0.011 2 days after surgery and p < 0.02 8 days
      after surgery), but not after laparoscopy. CONCLUSION: Impairment of cell
      mediated immune function after surgery was demonstrated especially in patients
      treated by laparotomy, as compared with those treated by laparoscopy.

PMID- 12799885
TI  - Laparoscopic subtotal cholecystectomy for severe cholecystitis.
AB  - BACKGROUND: In severe cholecystitis, laparoscopic cholecystectomy can be
      technically difficult, and is associated with an increased rate of procedure
      conversions and common bile duct lesions. METHODS: We investigated the safety and
      complications of laparoscopic subtotal cholecystectomy for severe cholecystitis
      in a medium- to long-term follow-up evaluation. Laparoscopic cholecystectomy was
      performed in 345 patients during a period of 64 months. In 46 of the patients
      (13.3%), a subtotal cholecystectomy was performed. The results were compared with
      data on laparoscopic cholecystectomy from 16,130 patients in 84 surgical
      institutes in Switzerland, collected prospectively by the Swiss Association for
      Laparoscopic and Thoracoscopic Surgery (SALTS). RESULTS: The median operating
      time was 93 min (range, 50-140) min. The overall rate of procedure conversions in
      acute cholecystitis was lowered significantly from 23.2% (SALTS) to 9.7%. There
      was no bile duct lesion, as compared with the rate of 0.8% in the SALTS data. In
      follow-up evaluations, fluid collections in 16 patients (35%) and residual
      gallstones in 6 patients (13%) were of no clinical relevance. CONCLUSIONS:
      Laparoscopic subtotal cholecystectomy for acute cholecystitis offers a simple and
      safe solution that prevents bile duct injuries and decreases the rate of
      conversion in anatomically difficult situations.

PMID- 12799886
TI  - Is laparoscopic colorectal surgery less invasive than classical open surgery?
      Quantitation of physical activity using an accelerometer to assess postoperative
      convalescence.
AB  - BACKGROUND: With the technical advances of recent years, the number of operative
      manipulations in the abdominal cavity by laparoscopic surgery is now considered
      to be the same as that using classical open surgery. The question has been raised
      whether laparoscopic colorectal surgery with lymphadenectomy improves the
      recovery compared to open surgery. METHODS: We compared patients' physical
      activity for 7 days postoperatively as measured with an accelerometer between
      laparoscopic-assisted colorectal resection (LAC, n = 32) and classical open
      colorectal surgery (OC, n = 30). RESULTS: Physical activity expressed as
      cumulative acceleration was significantly higher in the LAC than in the OC group
      on each postoperative day. The recovery time, defined as the day on which the
      cumulative acceleration recovered to 90% of the preoperative level, was
      significantly shorter (p < 0.05) in the LAC (3.4 +/- 1.2 days) than in the OC
      group (6.8 +/- 1.7 days). CONCLUSION: Our results showed that the duration of
      convalescence with LAC was significantly shorter than that with the OC procedure.
      Laparoscopic colorectal surgery appears to allow an earlier recovery after the
      operation than the classical open procedure, and it is less invasive as assessed
      by convalescence.

PMID- 12799887
TI  - The influence of periarterial papaverine application on intraoperative renal
      function and blood flow during laparoscopic donor nephrectomy in a pig model.
AB  - BACKGROUND: The transplantation of live donor kidneys harvested laparoscopically
      is associated with a higher incidence of delayed graft function than the
      transplantation of grafts harvested via the open technique. The delay is believed
      to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy
      (LDN). The aim of this study was to evaluate whether renal function and blood
      perfusion can be enhanced by the periarterial application of papaverine during
      LDN. METHODS: Renal function and blood flow were studied in a porcine model that
      included a total of 24 pigs (20-30 kg). In 12 of the pigs, urine output and
      creatinine clearance were determined as measures of renal function. In the other
      12 pigs, renal blood flow was determined using fluorescent-labeled microspheres.
      In each group, the pigs were randomized into two subgroups, one with and one
      without a perivascular injection of 50 mg papaverine. RESULTS: As compared to the
      controls, the animals receiving papaverine had a significantly higher urine
      output (3.1 +/- 1.6 vs 0.9 +/- 0.45 ml/h/kg; p = 0.02), superior creatinine
      clearance (2.22 +/- 0.5 vs 0.95 +/- 0.1 ml/min/kg; p = 0.038), and enhanced renal
      blood flow (4.9 +/- 2.2 vs 2.1 +/- 0.8 ml/min/g; p = 0.008). CONCLUSIONS: When
      applied to the tissue surrounding the renal artery, papaverine substantially
      improves renal function and blood flow during laparoscopic live kidney donation.
      Whether graft optimization during kidney procurement also translates into
      improved posttransplantation function remains to be established.

PMID- 12799888
TI  - Comparison of ultrasonic energy, bipolar thermal energy, and vascular clips for
      the hemostasis of small-, medium-, and large-sized arteries.
AB  - BACKGROUND: Advanced laparoscopic procedures have necessitated the development of
      new technology for vascular control. Suture ligation can be time-consuming and
      cumbersome during laparoscopic dissection. Titanium clips have been used for
      hemostasis, and recently plastic clips and energy sources such as ultrasonic
      coagulating shears and bipolar thermal energy devices have become popular. The
      purpose of this study was to compare the bursting pressure of arteries sealed
      with ultrasonic coagulating shears (UCS), electrothermal bipolar vessel sealer
      (EBVS), titanium laparoscopic clips (LCs), and plastic laparoscopic clips (PCs).
      In addition, the spread of thermal injury from the UCS and the EBVS was compared.
      METHODS: Arteries in three size groups (2-3, 4-5 and 6-7 mm) were harvested from
      freshly euthanized pigs. Each of the four devices was used to seal 16 specimens
      from each size group for burst testing. A 5-Fr catheter was placed into the open
      end of the specimen and secured with a purse-string suture. The catheter was
      connected to a pressure monitor and saline was infused until there was leakage
      from the sealed end. This defined the bursting pressure in mmHg. The ultrasonic
      shears and bipolar thermal device were used to seal an additional 8 vessels in
      each size group, which were sent for histologic examination. These were examined
      with hematoxylin and eosin stains, and the extent of thermal injury, defined by
      coagulation necrosis, was measured in millimeters. Analysis of variance was
      performed and, where appropriate, a Tukey's test was also performed. RESULTS: The
      EBVS's mean burst pressure was statistically higher than that of the UCS at 4 or
      5 mm (601 vs 205 mmHg) and 6 or 7 mm (442 vs 175 mmHg). EBVS had higher burst
      pressures for the 4 or 5-mm group (601 mmHg) and 6 or 7-mm group (442 mmHg)
      compared with its pressure at 2 or 3 mm (128 mmHg) ( p = 0.0001). The burst
      pressures of the UCS and EBVS at 2 or 3 mm were not significantly different. Both
      clips were statistically stronger than the thermal devices except at 4 or 5 mm,
      in which case the EBVS was as strong as the LC (601 vs 593 mmHg). The PC and LC
      were similar except at 4 or 5 mm, where the PC was superior (854 vs 593 mmHg).
      The PC burst pressure for 4 or 5 mm (854 mmHg) was statistically higher than that
      for vessels 2 or 3 mm (737 mmHg) but not different from the 6 or 7 mm pressure
      (767 mmHg). Thermal spread was not statistically different when comparing EBVS
      and UCS at any size (EBVS mean = 2.57 mm vs UCS mean = 2.18 mm). CONCLUSIONS:
      Both the PC and LC secured all vessel sizes to well above physiologic levels. The
      EBVS can be used confidently in vessels up to 7 mm. There is no difference in the
      thermal spread of the LigaSure vessel sealer and the UCS.

PMID- 12799890
TI  - Capnographic monitoring of ventilatory status during moderate (conscious)
      sedation.
AB  - BACKGROUND: Moderate (conscious) sedation is required to perform endoscopic
      procedures. Capnography provides a means for continuous, real-time monitoring of
      ventilation and may also decrease the incidence of oversedation. METHODS: A
      retrospective examination of all endoscopic procedures performed from January
      through December 2001 at our institution was undertaken to determine the
      potential benefits of capnographic monitoring. RESULTS: In 4,846 endoscopic
      procedures performed without capnography, adverse outcomes related to moderate
      sedation were noted in 14 cases (0.29%). A subset of patients at higher risk for
      moderate sedation was identified. There were no cases of oversedation in 600
      cases monitored with capnography. The complication rates were not significantly
      different for the two groups ( p = 0.30, NS). CONCLUSION: The addition of
      capnography during moderate sedation endoscopy does not appear to significantly
      lower anesthesia-related morbidity. However, in cases requiring moderate sedation
      for prolonged procedures, in older patients with comorbidities, or in instances
      where respiratory excursion of the patient is obscured from view, practitioners
      should nonetheless consider capnography.

PMID- 12799889
TI  - Laparoscopic surgery for stage I colorectal cancer.
AB  - BACKGROUND: This study analyzed the short- and long-term outcomes of laparoscopic
      surgery (LS) in patients with stage I colorectal cancer. METHODS: A total of 130
      patients with stage I colorectal cancer underwent LS between 1992 and 1999.
      Median follow-up was 61 months (range, 30-114). RESULTS: Oral intake was started
      on median postoperative day 1, and the median postoperative hospital stay was 8
      days. Postoperative complications included wound sepsis in eight patients (6.2%),
      anastomotic leakage in four patients (3.1%), and bowel obstruction in three
      patients (2.3%). Five patients developed recurrences. No port site recurrences
      were observed. The calculated 5-year survival rate was 97.9%. CONCLUSION: LS was
      shown to be technically feasible and oncologically sound for the treatment of
      patients with stage I colorectal cancer, and favorable short- and long-term
      outcomes were obtained.

PMID- 12799891
TI  - Clinical outcomes and changes in venous hemodynamics after subfascial endoscopic
      perforating vein surgery.
AB  - BACKGROUND: We evaluated the clinical results of subfascial endoscopic
      perforating vein surgery (SEPS) in patients with severe chronic venous
      insufficiency (CVI) (clinical class 4-6) and assessed the hemodynamic changes
      associated with SEPS using air plethysmography (APG). METHODS: Forty-five
      patients with severe CVI who had undergone SEPS were evaluated. Clinical score
      and venous hemodynamics, as measured by APG before operation and at 1 month and 1
      year after operation, were compared using the Wilcoxon signed rank test. Patient
      satisfaction (on a visual analogue scale of 0 to 100%) was also assessed.
      RESULTS: There were 29 men and 16 women; their mean age was 60 years (range, 37
      83). Thirty-five patients (78%) had active venous ulcers; the ulcers' mean size
      was 7.8 +/- 11.9 cm2 and the mean duration of ulceration was 9 +/- 10 months.
      There were no hospital deaths. Postoperative complications were uncommon (one
      groin wound infection and one case of thrombophlebitis). At a mean follow-up of
      15 +/- 9 months, 34 ulcers (97%) had healed. The cumulative ulcer healing was 82%
      at 3 months. There were five recurrent ulcers (15%). Significant improvement was
      seen in the clinical scores (10 +/- 3 before operation, 6 +/- 4 at 1 month, and 4
      +/- 3 at 1 year after operation). The venous filling index was also significantly
      improved after operation; this improvement was maintained at 1-year follow-up
      (7.36 +/- 6.23 ml/sec before operation, 3.63 +/- 3.90 ml/sec at 1 month, and 3.14
      +/- 2.06 ml/sec at 1 year). The degree of patient satisfaction was also
      remarkable, with 74 +/- 17% and 90 +/- 12% satisfaction at 1-month and 1-year
      follow-up, respectively. CONCLUSIONS: SEPS is a safe and effective treatment for
      patients with severe CVI. It leads to hemodynamic improvement, with rapid ulcer
      healing, and it is associated with a high degree of patient satisfaction.

PMID- 12799892
TI  - Three-port vs standard four-port laparoscopic cholecystectomy.
AB  - BACKGROUND: Since the first laparoscopic cholecystectomy (LC) was reported in
      1990, it has met with widespread acceptance as a standard procedure using four
      trocars. The fourth (lateral) trocar is used to grasp the fundus of the
      gallbladder so as to expose Calot's triangle. It has been argued that the fourth
      trocar is not necessary in most cases. Therefore, the aim of this study was to
      compare the three-port vs the four-port technique. METHODS: Between 1998 and
      2000, 200 consecutive patients undergoing elective LC for gallstone disease were
      randomized to be treated via either the three- or four-port technique. RESULTS:
      There was no difference between the two groups in age, sex, or weight. In terms
      of outcome, there was no difference between the two groups in success rate,
      operating time, number of oral analgesic tablets (paracetamol), visual analogue
      score, or postoperative hospital stay; however, the three-port group required
      fewer analgesic injections (nalbuphine) (0.4 vs 0.77, p = 0.024). CONCLUSION: The
      three-port technique is as safe as the standard four-port one for LC. The main
      advantages of the three-port technique are that it causes less pain, is less
      expensive, and leaves fewer scars.

PMID- 12799893
TI  - Intraoperative location of small gastrointestinal cancers with a handheld gamma
      probe.
AB  - The location of a small lesion must be precisely identified during laparoscopic
      surgery. A gamma probe that is usually used for navigating sentinel lymph nodes
      was evaluated for its usefulness in locating small gastrointestinal lesions (14
      gastric and 10 colonic). A total of 2 mCi of a Tc(99m)-labeled rhenium colloid
      was injected endoscopically around a tumor 16 h prior to surgery. During
      operation, the abdominal cavity was scanned using a handheld gamma probe
      (Navigator GPS, Tyco HealthCare, Norwalk, CT, USA). In all cases, the injection
      site was identified as the highest spot in the abdominal cavity, with 2585 counts
      per second on average (range, 910-8800 counts per second). The highest count in a
      lymph node was 637 per second on average. The gamma probe is a useful tool for
      identifying small gastrointestinal lesions during open and laparoscopic
      operations.

PMID- 12799894
TI  - Thoracoscopic Belsey fundoplication with 5-year outcomes.
AB  - BACKGROUND: To determine the indications for a minimally invasive thoracic
      technique in gastroesophageal reflux disease (GERD), we conducted a retrospective
      review of outcomes with our first 21 thoracoscopic Belsey fundoplications.
      METHODS: A thoracoscopic Belsey fundoplication was completed in 21 patients (12
      males, 9 female; ages, 38-83 years). Preoperative evaluation revealed 13 primary
      motility disorders, 9 strictures, and 3 epiphrenic diverticuli. Six patients had
      previous gastric surgery. Sixteen patients underwent 20 ancillary procedures
      (esophagomyotomy, 14; excision of diverticulum, 2; lung volume reduction, 2;
      prosthetic diaphragmatic repair, 1; and Thal-Woodward esophagoplasty, 1).
      RESULTS: Mean follow-up was 75.6 months (range, 67-85 months). There was one
      operative death (4.8%). Early morbidity included two esophageal leaks (9.8%).
      Late morbidity included three patients (15.7%) with persistent dysphagia and five
      patients (26%) with recurrent GERD. CONCLUSION: Thoracoscopic Belsey
      fundoplication was associated with a high morbidity and recurrence rate in our
      long-term experience.

PMID- 12799895
TI  - Laparoscopic cholecystectomy for triple gallbladder.
AB  - A very rare case involving true triplication of the gallbladder in a 38-year-old
      man with no other congenital abnormalities is reported. All three gallbladders
      had signs of chronic inflammatory disease and lithiasis. Acute cholecystitis and
      a double gallbladder were diagnosed preoperatively, but the diagnosis of a second
      accessory gallbladder was made only at the time of surgery. The patient underwent
      successful laparoscopic cholecystectomy. When a triplicate gallbladder is
      encountered, complete dissection of Calot's triangle and intraoperative
      cholangiographic evaluation should be performed to prevent damage to the biliary
      duct system. All three gallbladders should be removed to avoid unnecessary
      reoperation. All of this can be accomplished readily by laparoscopic surgery.

PMID- 12799896
TI  - Portal vein thrombosis.
AB  - Portal vein thrombosis (PVT) is a complication of hepatic disease and a
      potentially lethal complication of splenectomy. The reported incidence of this
      complication is low (approximately 1%). However, its true incidence may have been
      underestimated due to difficulty in making the diagnosis. Herein we report the
      case of a 19 year-old woman who presented with a 2-year history of idiopathic
      thrombocytopenic purpura (ITP). Because she had become refractory to medical
      therapy, she underwent laparoscopic splenectomy. She was discharged on
      postoperative day 2 after an uncomplicated procedure. She did well, complaining
      only of mild backache, until postoperative day 21, when she presented with
      nausea, vomiting, and leukocytosis. CT showed PVT and superior mesenteric vein
      thrombosis. Despite heparin and fluid administration, her condition worsened. At
      laparotomy, she had diffuse small bowel edema and congestion. At a second-look
      procedure 24 h later, nearly all her jejunum and ileum were necrotic. After three
      procedures, she was left with 45 cm of proximal and 10 cm of distal small bowel.
      Bowel continuity was restored 8 weeks later. She continued on warfarin
      anticoagulation therapy for 1 year. Postsplenectomy PVT is most often seen
      following splenectomy for myeloproliferative disorders and almost never after
      trauma. The large splenic vein stump and the hypercoagulable state in patients
      with splenomegaly are thought to be contributory. The presentation of PVT is
      vague, without defining signs or symptoms. Color-flow Doppler and contrast
      enhanced CT scans are the best methods for the nonoperative diagnosis of PVT.
      Aggressive thrombolysis offers the best hope for clot lysis and maintenance of
      bowel viability. Even vague symptoms must be considered seriously following
      splenectomy.

PMID- 12799897
TI  - Laparoscopic resection of a periampullary villous adenoma.
AB  - BACKGROUND: Adenomas of the duodenal papilla are rare lesions. Because of their
      malignant potential, resection is mandatory. Options for resection include
      endoscopic resection, transduodenal local excision, and pancreaticoduodenectomy.
      This report details a case of periampullary villous adenoma diagnosed
      endoscopically and resected laparoscopically via a transduodenal approach. CASE
      REPORT: A healthy 75-year-old woman with heartburn underwent an upper endoscopy
      for vague right upper abdominal pain. A periampullary tumor was diagnosed.
      Endoscopic biopsy results were consistent with a villous adenoma, and endoscopic
      ultrasound showed distal bile duct involvement. The patient underwent
      laparoscopic transduodenal local excision of the tumor with biliary
      reconstruction. CONCLUSIONS: Laparoscopic transduodenal resection of
      periampullary lesions provides advantages similar to those of an endoscopic
      resection by removal of the tumor using minimally invasive techniques. In
      addition, laparoscopic surgery maintains the surgical tenents of open
      transduodenal resection with en bloc tumor resection including the adjacent
      duodenal wall and ductal structures as necessary. As noted in this case,
      laparoscopic techniques resect ampullary lesions involving the ductal structures
      as well. Laparoscopic transduodenal ampullectomy is a valuable treatment option
      for benign and selected premalignant ampullary lesions.

PMID- 12799898
TI  - Treatment of pulmonary sequestration by video-assisted thoracic surgery (VATS).
AB  - Pulmonary sequestration is a rare malformation of the respiratory tract that
      accounts for 0.15-6.4% of all congenital lung anomalies. Treatment requires
      resection of the lesion, provided that there is no technical contraindication.
      The lesion should first be evaluated using video thoracoscopy and then resected
      whenever possible by video-assisted thoracic surgery (VATS). We report a case of
      extralobar pulmonary sequestration in a 48-year-old woman. She underwent
      lobectomy by VATS and achieved an excellent outcome.

PMID- 12799899
TI  - Anaplastic lymphoma kinase negative sarcomatoid variant of anaplastic large-cell
      lymphoma presenting as a malignant fibrous histiocytoma.

PMID- 12799901
TI  - Co-ordination of Ca(2+) signalling in mammalian cells by the new Ca(2+)-releasing
      messenger NAADP.
AB  - Ca(2+) signalling is one of the most important means in mammalian cells of
      relaying the action of hormones and neurotransmitters. The great diversity of
      agonist-induced Ca(2+) signatures, visualized by optical imaging techniques, can
      be explained by the production of intracellular messengers triggering Ca(2+)
      release from internal stores and/or by different coupling of Ca(2+) release to
      Ca(2+) entry. Several messengers, such as inositol trisphosphate and cyclic ADP
      ribose, have been identified to date. More recent studies have reported the
      important role of a newly discovered Ca(2+) releasing messenger, nicotinic acid
      adenine dinucleotide phosphate (NAADP). These studies have shown important
      interactions of these messengers in the generation of specific Ca(2+) signals.
      NAADP acts at a very low concentration and seems to have a key role in
      sensitising cyclic ADP-ribose and inositol trisphosphate receptors. These points
      will be discussed in the present review.

PMID- 12799902
TI  - Characterization of stretch-activated ion currents in isolated atrial myocytes
      from human hearts.
AB  - To explore further the mechanisms that may underlie cardiac arrhythmia, we
      analysed stretch-activated ion currents in human atrial myocytes. Longitudinal
      stretch of freshly isolated atrial myocytes prolonged the duration of action
      potentials, depolarized the resting membrane potential and caused extra action
      potentials. Under voltage-clamp conditions, the amplitude of stretch-induced
      transmembrane currents increased reversibly with the intensity of stretch.
      Stretch-activated currents ( I(SAC)) had a reversal potential of 0 mV and were
      insensitive to substitution of Cl(-) with aspartate ions in the extracellular
      fluid. I(SAC) was suppressed by 5 micro M gadolinium (Gd(3+)). Furthermore,
      mechanical stretch decreased transmembrane ion fluxes through L-type calcium
      channels (I(Ca,L)). This reduction of I(Ca,L) was inhibited by dialysing the
      cells for 5 min with 5 mM BAPTA prior to application of stretch. In contrast,
      both BAPTA and removal of Ca(2+) from the extracellular bathing solution had no
      significant effect on stretch activation of I(SAC). These findings suggest that
      non-selective cation channels in human atrial myocytes are sensitive to
      mechanical stimulation. We propose that activation of transmembrane influx of
      cations, preferentially Na(+), by local stretch may play a role in cardiac
      arrhythmia.

PMID- 12799903
TI  - Functional characterization of an episodic ataxia type-1 mutation occurring in
      the S1 segment of hKv1.1 channels.
AB  - Voltage-gated potassium channels (Kv) play important roles in neurotransmission,
      nerve cell excitability and disease. Several missense mutations in the Kv1.1 gene
      have been associated with episodic ataxia type-1 syndrome (EA-1), which is
      characterized by continuous myokymia, episodic attacks of ataxic gait and spastic
      contractions of skeletal muscles. In this study we show that I177N, an EA-1
      mutation located in S1 segment, alters the expression and gating properties of
      the channel expressed in Xenopus oocytes. In particular, it reduces ~17-fold the
      current amplitude, accelerates ~4-fold the deactivation kinetics of the channel
      and shifts the voltage dependence of activation ~60 mV to more depolarized
      potentials. Single-channel recordings also showed that the mean open duration of
      I177N channels was ~2.6-fold smaller than the wild-type. These results
      demonstrate that both reduced current levels and specific gating defects are the
      likely causes of EA-1 symptoms in patients bearing the I177N mutation.
      Furthermore, the data suggest that the I177N substitution may alter the gating
      properties of the channel that are specifically defined by the S1 segment.

PMID- 12799904
TI  - [Acute treatment of episodic childhood tension-type headache with flupirtine and
      paracetamol - a double-blind crossover-study].
AB  - BACKGROUND: About 10% of all schoolchildren are suffering from migraine and 50%
      from tension-type headache. Headache of acute onset usually will be treated with
      analgesic substances like paracetamol, acetylsalicylic acid or ibuprofen, the
      first one being the reference drug for tension-type headache in childhood. In
      case of lacking improvement or side-effects there is demand for an alternative
      safe substance for the acute analgesic therapy. METHODS: In a double-blind
      randomised investigation flupirtine and paracetamol were given in two consecutive
      attacks of episodic tension-type headache. 30 children, 6-12 years old, were
      included. Dosage was determined according to age and weight. The children
      documented the acute headache intensity and duration in a special diary. RESULTS:
      Headache intensity was reduced during 2 h after intake in 89% of the 19 children
      treated. The reduction was 6,5 to 3,1 for flupirtine and 6,9 to 3,3/10 for
      paracetamol. There was no statistically significant difference between the two
      substances. Relevant side-effects could not be observed. CONCLUSION: Flupirtine
      has shown a convincing clinical effect treating acute episodic tension-type
      headache for children. The substance was well tolerated by the patients. In
      addition, flupirtine provides a high degree of safety.

PMID- 12799905
TI  - [Functional capacity after peripheral nerve lesion: significance of pain
      syndromes].
AB  - INTRODUCTION: The loss of functional capacity by peripheral nerve lesion is easy
      to be estimated: A certain neurologic dysfunction results in a characteristic
      reduction of the former individual capacity. In contrast, the effect of
      accompanying pain to every-day life and working ability is not known exactly. In
      this study, we compared the results of judgement in nerve lesions under the
      circumstances of additional pain syndromes. METHODS: From January 1994 until
      December 1998 we saw 57 patients with peripheral nerve lesions, part of them with
      an additional pain syndrome. Beside conventional neurological examination a
      detailed pain analysis has been done. RESULTS: Lesions of the median or ulnar
      nerves showed regularly disturbances in neurological functions (10/14 for the
      median nerve, 13/16 for the ulnar nerve). Astonishing is the fact, that serious
      pain after nerve lesion only occurs in cases of partial nerve lesion. We saw
      neuralgias in 6 patients with ulnar neuropathy, in three cases of median nerve
      lesions we could see severe neuralgia (causalgia we found in 3 cases of ulnar
      neuropathy, in 6 cases after Median Nerve lesion). Patients with a lesion of the
      central plexus brachialis showed in 10 of 11 cases an additional pain syndrome.
      Other nerves have been affected more rarely. For the judgement of the loss of
      earning capacity we saw an additional pain related diminuition of at least 10%
      compared to those patients without pain problems. CONCLUSIONS: The common grading
      scales for peripheral nerve lesions are not suitable in cases accompanied by an
      additional pain syndrome. Beside a functional deficit the effect of severe pain
      in these patients has to be estimated. On an average, patients with additional
      pain-problems get a 10% extended loss of earning capacity, even more in
      particular cases.

PMID- 12799906
TI  - [Classification of chronic pain. Quantification and grading with the Mainz Pain
      Staging System].
AB  - INTRODUCTION: Chronic pain is an individually variable experience, incorporating
      physical, psychological and social dimensions. Chronic pain occurs in a broad
      spectrum of severity; therefore, a grading procedure is of crucial importance in
      clinical research and in epidemiologic studies. The Mainz Pain Staging System is
      an interview-administered, multi-dimensional measure of chronic pain severity.
      The system suggests grading chronic pain in terms of 4 axes: time (persistence),
      spreading of pain site, medication use, and health care utilization. The whole
      scale consist of 10 items. The resulting score is used to classify the pain
      problem in three stages (I, II, III). Analysing the broader validity and
      parametric properties of the staging system is the purpose of the present study.
      METHODS: The staging system and psychosocial data were administered to 542
      consecutive patients of different diagnoses who attended one of six pain clinics
      in the year 1995/96. In a time period of 3 months since first contact, treatment
      procedures were registered. Three months after first contact patients rated the
      effectiveness of treatment concerning reduction of pain intensity. RESULTS:
      According to the criteria of the staging system 25% of the sample belonged to
      each stage I and stage III, whereas 50% were classified to stage II. As a measure
      of validity, chronic pain status demonstrated significant correlation with
      psychological impairment, disability and time off work, whereas there was no
      correlation to pain intensity and persistence of pain. Surprisingly we found no
      difference in amount and quality of treatment between patients who were graded as
      severe pain patients (stage III) and the other stages. Furthermore, effectiveness
      of treatment also did not differ between the three stages. We made several
      proposals for optimizing the staging system. CONCLUSION: Given the high
      prevalence of recurrent and chronic pain as well as the broadness of severity, an
      important issue on further research is identification of factors which influence
      the chronification process. For this purpose improved measures of graded
      classification of pain status are needed.

PMID- 12799908
TI  - [Long-term treatment with flupirtine. 7 years continuous therapy of a chronic
      pain syndrome].
AB  - CASE REPORT: The worker O.H., born in 1959, had in 1992 an accident as a car
      driver. His injuries were a severe acceleration trauma of the cervical spine with
      rupture of the longitudinal ligament, a concussion of the brain, and an eye
      injury. THERAPY: After the emergency treatment, the multidisciplinary management
      could not resolve the persistent musculoskeletal cervicocephal and -brachial pain
      syndrome. The long-term application of 100 mg flupirtine tid improved the chronic
      pain state for 50-60%. Due to this regimen, the patient could be rehabilitated.

PMID- 12799910
TI  - [Not Available].

PMID- 12799911
TI  - [Postoperative pain therapy in children].

PMID- 12799909
TI  - [Not Available].

PMID- 12799912
TI  - [Multidisciplinary treatment of chronic pain in the German federal state of
      Northrhine-Westphalia].
AB  - BACKGROUND: Multidisciplinary treatment of patients with chronic pain in pain
      centers was studied. The conditions of all multidisciplinary pain centers in the
      German federal state of Northrhine-Westphalia (NRW), an area of about 17 million
      inhabitants, were investigated. METHODS: The study included data from the index
      of all registered multidisciplinary pain centers in the years 1992, 1994, 1996,
      and empirical data of a written (questionnaire) in 1993 from physicians and
      psychologists working as specialists in the pain centers studied. RESULTS:
      Several new pain centers (inpatient wards, outpatient pain clinics) had been
      built up in the last years in Northrhine-Westphalia. The pain centers are
      organized mostly as outpatients' departments. Departments of psychological
      treatment of chronic pain are usually integrated into pain clinics. In recent
      years, the use of qualified psychological pain treatment by psychologists has
      been under-represented. Pain treatment evaluation is carried out by considering
      the structure of supply in pain management, the qualification and specialization
      of physicians and psychologists and the amount of treated patients with chronic
      pain. The 57 pain centers in the investigated area reported on about 120,000
      patients with chronic pain a year, who were treated in multidisciplinary pain
      centers. The estimated number of patients with chronic pain in Northrhine
      Westphalia was approximately 850,000 patients (4 million in Germany).
      CONCLUSIONS: There is an existing network of multidisciplinary pain centers in
      Northrhine-Westphalia. If we consider the estimated number of 850,000 patients
      with chronic pain in this area, the low number of yearly treated patients
      (120,000) indicates, that the capacity of multidisciplinary pain centers is
      inadequate for the demand of multidisciplinary treatment of patients with chronic
      pain in Northrhine-Westphalia.

PMID- 12799913
TI  - [The prevalence of pain in the German population: results of population-based
      studies with the Giessen Subjective Complaints List (Giessener Beschwerdebogen
      GBB)].
AB  - OBJECTIVE: Pain is one of the most frequent physical complaints worldwide.
      Empirical data on the prevalence of chronic pain is considerable. However,
      compared with the large number of epidemiological studies published in North
      America, Great Britain and particularly in Scandinavia, there has been relatively
      little equivalent research in Germany to date. METHODS: In two separate
      population-based cross-sectional studies conducted in 1975 (n=1.597, 18-60 years)
      and 1994 (n=2.148, 18-60 years) using the Giessen Subjective Complaints List
      (Giessener Beschwerdebogen GBB), data was collected on current pain in various
      parts of the body (limbs, back, neck, head, stomach). RESULTS: The frequency
      scores for pain varied according to localization between 32.4% (stomach pains
      1975) and 67.3% (headaches 1994). Between the two measurement dates there was an
      increase in overall prevalence particularly for pains in the neck, head and
      limbs. At the same time we found a decrease in the proportion of severe pain
      symptoms. There were also considerable variations in pain experience according to
      age and gender: the frequency of pain increases with age (especially in limbs,
      back and neck). Women register more pain than men (particularly in head and
      neck), although the influence of gender decreases from 1975 to 1994. There are
      other sociodemographic variables like marital status, educational level,
      occupation or living in East/West Germany which influence the pain prevalence.
      CONCLUSIONS: Pain in differing parts of the body is a serious problem in the
      German population. However, the prevalence of pain is strongly dependent on
      sociodemographic factors (especially age, gender and living in East/West
      Germany), the localization of pain in the body and the grading of pain. Future
      epidemiological research should take these differential aspects into account.

PMID- 12799914
TI  - [The Marburg questionnaire on habitual health findings--a study on patients with
      chronic pain].
AB  - BACKGROUND: Subjective well-being is an essential ingredient in the quality of
      life concept. The Marburg questionnaire, a seven item scale for the assessment of
      the trait dimension of well-being, claims to possess good psychometric
      properties. This is investigated in two studies with chronic pain patients.
      METHODS: The first study utilizing a prospective, randomized, and controlled
      design, served to find out the effects of a pain management program. Included
      were 236 patients with a diagnosis of chronic low back pain (Toronto
      classification) or tension type headache (IHS classification). Study 2 employed a
      cross-sectional design and relied on the data of 186 patients mainly with pain in
      the back and the head who had filled in a pain questionnaire provided by the
      Schmerztherapeutisches Kolloquium, a German pain society. RESULTS: Across the
      studies, internal consistency of the scale with Cronbach's alpha=0.91 proofed to
      be very satisfactory; retest-reliability after an interval of eight weeks came up
      to r(tt)=0.81. The scale is one dimensional and demonstrates good replicability
      of the dimensional structure. The factor accounts for 65% of the variance of the
      test scores. Moreover, the scale is sensitive to change, and, therefore, can be
      used as an assessment tool in interventions that aim at an improvement of well
      being. Interrelations with variables indicating chronicity support the concept of
      construct validity. This refers to the stage algorithm provided by the pain
      clinic in Mainz, to the affective dimension of the pain experience, to
      disability, depression, and inability to work. CONCLUSION: The good psychometric
      quality of the questionnaire along with its brevity allows its application as
      part of a quality of life assessment.

PMID- 12799915
TI  - [Differential diagnosis of otalgia].
AB  - BACKGROUND: Otalgia is the sensation of pain in the ear, while referred otalgia
      is pain felt in the ear but originating from a nonotologic source. Ear pain is a
      diagnostic problem when examination of the ear shows no pathology. This article
      reviews the anatomic basis for referred otalgia and shows the common etiologies
      responsible for this symptom. OTALGIA: Pain in the ear can be caused by
      inflammation of the external meatus or the middle ear. Nonotogenic otalgia may be
      due to referred or reflex pain, neuralgia, or to a psychogenic problem. Otalgia
      may be referred also from primary carcinoma of the head and neck. A thorough
      understanding of the anatomy of the head and neck is required. A basic knowledge
      of neuroanatomy, with emphasis on the cranial nerves, their course, distribution,
      and function, is also necessary. Referred pain is due to irritative lesions
      involving the fifth, ninth, or tenth cranial nerve and spinal nerves C2 and C3.
      If pathologic problems in the area supplied by these nerves have been ruled out,
      the neuralgia should be considered in the differential diagnosis. Psychogenic
      factors must be identified and treated before any type of surgical therapy is
      recommended. The complexity of this field may sometimes require the treating
      physician to call for consultations from colleagues in the fields of oral
      surgery, orthopaedics, neurology, or neurosurgery.

PMID- 12799916
TI  - [The cervicogenic headache from the spiral surgery point of view--a pilot study].
AB  - In a retrospective analysis of 299 consecutive patients with degenerative
      cervical spine disease the incidence of cervicogenic headache and the results of
      conservative and operative therapy have been investigated. Cervicogenic headache
      was noted in 117 of 299 patients (40%). 73 of those patients were treated
      conservatively. The cervicogenic headache resolved in 10% or improved in 27% and
      remained unchanged in 63% of the patients. 44 of these patients were operated by
      ventral discectomy, which was indicated in case of neurological deficit and
      painful shoulder-arm syndrome refractory to conservative treatment. In none of
      these patients the operation was indicated by the cervicogenic headache. In the
      postoperative follow-up with a mean of 6 months the headache resolved in 20%,
      improved in 60% and remained unchanged in 20% of the patients. These results
      suggest the existence of a cervicogenic headache, i.e. a headache due to
      disorders of the cervical spine, and the chance of successful operative
      treatment.

PMID- 12799917
TI  - [Chronic pain. Organizational aspects in the treatment].

PMID- 12799918
TI  - [Drug-induced headache--pathomechanisms of addiction].
AB  - The pathogenesis of drug abuse in patients suffering from drug-induced headache
      is not known in detail. It is unclear whether drug abuse in chronic daily
      headache should be classified as a form of drug dependence. Current findings
      concerning the neurobiological correlates of addictive behavior and affective
      disorders point to the importance of monoaminergic dysregulation, especially a
      dysfunction of central serotonergic neurotransmission. We reviewed the literature
      on drug-induced headache and examined hypothetical pathomechanisms of addiction.
      Drugs causing drug-induced headache such as paracetamol, coffein and ergotamine
      interfere with behavior patterns or neurotransmitter systems that are also
      affected by drugs of abuse. Several drugs that ameliorate acute headache interact
      with central serotonergic neurotransmission and may affect anxiety and depression
      in patients with chronic daily headache. Non human primate and human studies
      revealed mechanisms of serotonergic dysfunction in drug dependence, which may
      also be relevant for drug-abuse in medication-induced headache. Medication
      induced dysfunction of monoaminergic, especially serotonergic neurotransmission,
      may affect drug dependence by exacerbating mood disorders. Further studies are
      necessary to assess serotonergic neurotransmission in patients with drug-induced
      headache and abuse of medication.

PMID- 12799919
TI  - [Animal studies on neuropathic pain: the role of cytokines and cytokine receptors
      in pathogenesis and therapy].
AB  - When pain becomes chronic this is a process that takes place at several levels of
      the peripheral and central nervous systems. In recent years, proinflammatory
      substances like bradykinin, prostaglandins and signal molecules like cytokines
      have been identified as allogenic factors. In the present paper we examined
      whether cytokines play a role also in non-inflammatory peripheral nerve lesions,
      i.e. whether they are of importance in the causation of pain in general and
      whether their antagonists can be used therapeutically. The development of pain
      after peripheral nerve lesion in animal models follows the process of Wallerian
      degeneration. During Wallerian degeneration the expression of proinflammatory
      cytokines in the nerve is upregulated. Here we studied the temporal course of
      cytokine expression with several different analytical methods, analyzing tumor
      necrosis factor-alpha (TNF) and interleukin-beta (IL-beta) in the mouse model of
      chronic constrictive injury (CCI) of the sciatic nerve. This model is associated
      with reproducible pain related behavior in the animals. We found an early
      increase of TNF 12 hours after injury. Neutralizing antibodies to TNF were able
      to reduce the hyperalgesia that evolved due to the nerve injury. As TNF exerts
      its effects via two receptors, TNF receptor 1 (TNF-R1) and TNF receptor 2 (TNF
      R2), we also investigated, which of the receptors is relevant to the causation of
      pain in this model. It turned out that antibodies to TNF-R1, but not to TNF-R2
      reduced hyperalgesia, indicating that TNF-R1 is the receptor concerned.
      Neutralizing antibodies to IL-1 receptor and to IL-6 receptor also reduced pain
      related behavior. These results lead to the conclusion that proinflammatory
      cytokines are involved not only in inflammatory pain but also in neuropathic
      pain. Therapeutic strategies involving cytokine inhibition have been tested
      experimentally and are already being used in preliminary clinical studies in
      immune-mediated diseases. In the future, they might be a useful addition to the
      range of treatments for patients with neuropathic pain.

PMID- 12799921
TI  - [Postdural puncture headache: diagnosis, prevention and therapy].
AB  - Lumbar puncture (LP) is a routine technique performed for a variety of
      procedures, e.g. diagnosis, administration of drugs, myelography and spinal
      anaesthesia. Postdural puncture headache is a common complication (30-40% in
      diagnostic LP). Prevention can be accomplished by using small-gauge needles (< or
      = 25 G) or pencil-point needles (22 G). Therapy should be carried out in a
      stepwise approach. The first step is bedrest, use of analgetics, i.v. fluids and
      an adequate guidance of the patient. The second step comprises special drug
      therapy. Several methods of pharmacologic management have been presented in the
      literature, but most of these are case reports. There is a lack of large double
      blind placebo-controlled studies. Theophylline, caffeine, ACTH and sumatriptan
      are potentially promising agents for the treatment of postdural puncture
      headache. The efficacy of theophylline has been proven in a double-blind and
      placebo-controlled study. There are a few studies and case reports reporting that
      caffeine p.o. and i.v. is effective in the treatment of postdural puncture
      headache, but recurrence of headache after caffeine therapy is frequent. ACTH
      acts on a complex hormonal system. The treatment with sumatriptan has been
      reported in only a few case reports. The third step, and one of the most
      effective treatments of postdural puncture headache, is the epidural blood patch.
      The success rate ranges between 80 and 97%.

PMID- 12799920
TI  - [Reduction of spastic increased muscle tone in multiple sclerosis by the
      nonopioid analgesic flupirtine].
AB  - OBJECTIVES: A reduction of muscle tone in rats can be found after intraperitoneal
      or intrathecal injection of flupirtine in analgetic doses. However, a muscle
      relaxing effect in patients with spasticity has not yet been shown. In this study
      we investigated whether flupirtine can reduce the increased muscle tone in
      patients with spasticity. METHODS: The muscle-relaxing effect of flupirtine was
      compared to that of tetrazepam and of placebo in a randomised, double-blind,
      cross-over design. Altogether 9 patients with spastically increased muscle tone
      of the lower limbs were investigated. The EMG activity integral of the rectus
      femoris muscle was chosen as quantitative parameter for degree and change of
      muscle tone. The EMG activity integral was measured using a dynamic bicycle
      ergometer 60, 120 and 180 min after administration of the tested drugs. The
      degree of spasticity was measured as the quotient of the EMG activity integral of
      the active and passive rotation phase. This quotient is inversely proportional to
      the spastic muscle activity. RESULTS: With flupirtine a significant increase in
      the EMG activity integral was found after 60 min (maximum effect). From 120 min
      it showed a slow decline. With tetrazepam the maximal effect was reached after
      180 min. Placebo did not change the EMG activity integral during the experiment.
      CONCLUSION: These results support the thesis that flupirtine has a muscle
      relaxing effect in patients with pathologically increased muscle tone.

PMID- 12799922
TI  - [A pharmaceutical of the century will be 100. A historical vignette on the
      introduction of acetylsalicylic acid to the market in 1899].
AB  - This article describes the historic roots of acetylsalicylic acid (ASA) from the
      first experiments at 1800 until the introduction into the pharmaceutical market
      in 1899. In 1869, Hermann Kolbe enlightened the chemical structure of salicylic
      acid, which was used at that time as an analgetic and antipyretic drug. Because
      of the side effects, for example the irritation of the stomach, analytical
      chemists and pharmacologists searched for chemical modifications. In August 1897
      Felix Hoffmann (1868-1946) was successful in acetylizing the salicylic acid to
      acetylsalicylic acid (ASA). Between 1897 and 1899 Kurt Witthauer (1865-1911)
      collected clinical data and experiences on the efficiency of ASA as an analgetic
      and antipyretic drug. In 1899 ASA was introduced into the pharmaceutical market
      as Aspirin and became soon one of the most successful drugs of its time. The
      indication exceeds analgesia in the mean time and to prophylaxis of myocardial
      ischaemia or cerebral stroke, among others.

PMID- 12799923
TI  - [Ethics in medicine. Needs and forms].

PMID- 12799924
TI  - [What do we know about the prevalence of pain caused by malignancy?].
AB  - BACKGROUND: Since there is no epidemiologic assessment of the frequency of pain
      caused by tumor in Germany, tumor-pain-prevalence is estimated indirectly on the
      basis of mortality and median survival. Knowing that about 50% of all patients
      having metastases or incurable locoregional recurrence suffer from pain every
      day, the product of median survival times mortality was calculated to achieve the
      number of patients' days with tumor-caused pain per year (82,710,690 days in
      Germany 1995). By division with 365 (days), it is calculated that 226,605
      patients require tumor pain related treatment at one day in Germany. Another
      calculation based on Bonica's publications that 60-90% of patients suffering from
      advanced cancer are having pain and based on an estimated tumor prevalence
      1989/90 revealed a tumor pain prevalence of 221,826. DISCUSSION: Thus both
      methods result in the estimation, that about 220,000 patients require tumor-pain
      related treatment at one day in Germany.

PMID- 12799925
TI  - [Time used for outpatient tumor pain therapy].
AB  - OBJECTIVE: The insufficiency of pain therapy for cancer patients is a frequent
      complained. One reason for this deficit may be the great amount of time required
      for the management of patients with far advanced diseases. The objective of this
      paper is the calculation of time for this therapy. METHODS: All relevant data on
      pain treatment of 126 patients were followed up in an anaesthesiology outpatient
      facility and their therapy was recorded retrospectively over a period of 52
      months. RESULTS: During a period of 18,798 observation days 1,634 pain therapy
      consultations were performed, on average 13 per patient (1 to 95). The mean
      duration of therapy was 149 days. The percentage of consultations at home was
      46%, most of them (80%) were scheduled, the remaining 20% were emergency
      consultations that were immediately necessary, at night or on Sundays.
      Altogether, the mean time for therapy including travel time was about 7 h until
      the end of the therapy. Only 13.5% of patients died in a hospital. CONCLUSION:
      Because of the great amount of time necessary for cancer pain therapy close
      collaboration of all physicians involved in analgesic/palliative care is
      essential. This requires a good basic knowledge of all colleagues about the
      specialties of cancer pain therapy as well as good commitment by the pain
      specialists.

PMID- 12799926
TI  - [WHO recommendations for treatment of tumor pain. Development of an evaluation
      system].
AB  - AIM OF THE STUDY: Evaluation of the observance of the World Health Organization
      guidelines for cancer pain management is a prerequisite for further research into
      the effectiveness and acceptability of the guidelines. METHODS: In a nationwide
      survey 172 physicians in pain management and oncological units documented
      transdermal therapy with fentanyl. From October 1996 to May 1997, 591 patients
      were included. A total of 148 patients had already received transdermal fentanyl
      before inclusion in the survey, and no data on previous analgesic management were
      available for 7 patients. For 436 patients analgesic therapy before initiation of
      transdermal fentanyl was evaluated. The last analgesic regimen documented by the
      treating physician was rated by three physicians from our pain clinic
      independently of each other. A rating system with four items (potency of
      analgesic according to the analgesic ladder of the WHO guidelines, prescription
      of a rescue medication, combination of nonopioids with opioids, inadequate
      combinations of analgesics) and a global rating (the analgesic regimen is
      considered adequate, sufficient or inadequate) was used. RESULTS: Good agreement
      was reached for classification according to the analgesic ladder, prescription of
      rescue medication and for inadequate drug combinations. The ratings on
      combinations with nonopioids showed more differences. The scores for the global
      assessment showed a wide difference between raters, with agreement on the same
      score for only 36.2% (raters 1 and 3), 36.7% (raters 2 and 3) and 55.5% of the
      patients (raters 1 and 3). CONCLUSIONS: A global assessment score is not useful
      for evaluation of guideline acceptance. A more differentiated scoring system was
      developed for further studies that includes the analgesic ladder and other
      aspects of the WHO guidelines in a 10-point score.

PMID- 12799927
TI  - [Opioid therapy in Austria: results and analysis of a survey].
AB  - INTRODUCTION: Many causes are given as the main reason for inadequate pain
      therapy. The objective of our study was to demonstrate the current position of
      doctors in general practice all over Austria who prescribe prescriptions.
      METHODS: A total of 5,359 questionnaires were sent out to general practitioners
      in all federal states of Austria. These questionnaires contained 21 main
      questions on subjects relevant to pain therapy. RESULTS: On average, 16% of all
      general practitioners returned the questionnaires; 89.3% of these are acquainted
      with the WHO graduated scale, 87% have prescribed strong opioids. Old prejudices
      such as concerns about the side effects are hardly to be found now. Modern
      therapy strategies are used. CONCLUSION: Based on the data at hand, pain therapy
      for patients should be excellent. The reality, however, is somewhat different.
      The large number of doctors who did not reply makes it enormously difficult to
      make a statement about the position of pain therapy in Austria.

PMID- 12799928
TI  - [Switching opioids to transdermal fentanyl in a clinical setting].
AB  - INTRODUCTION: The use of transdermal fentanyl is gaining in importance in the
      management of cancer pain. We describe the reasons for switching opioid
      medication to transdermal fentanyl in a pain management unit. METHODS: Case
      records of patients treated with transdermal fentanyl in our pain clinic were
      evaluated retrospectively. Conversion ratios were calculated from the opioid
      dosage before and after conversion. Pain intensities were assessed on a numeric
      rating scale (NRS 0: no pain, 10: worst pain imaginable). RESULTS: From October
      1995 to December 1997 101 patients received transdermal fentanyl. Thirty-six
      patients had been treated with transdermal fentanyl before admission to our pain
      clinic, and relevant information was missing for one patient, so 64 patients were
      evaluated. Opioid therapy was switched to transdermal fentanyl during in-patient
      treatment for 53 patients and during out-patient treatment for 11 patients.
      Before conversion patients were treated with slow-release morphine (48%),
      immediate-release morphine (17%), buprenorphine (11%), tramadol (11%),
      levomethadone (5%), tilidine/naloxone (5%) and piritramid (3%). Reasons for
      opioid rotation were inadequate pain relief ( 33%), the patients' wish to reduce
      oral medication (20%), gastrointestinal side effects such as nausea (31%),
      vomiting (13%) and constipation (19%), dysphagia (27%) or others. Reduction of
      side effects was reported by 10 of 19 patients. In 12 of 21 patients, in whom the
      medication was switched because of inadequate pain relief, a reduction in pain
      intensity was reported. DISCUSSION: Conversion to transdermal therapy may
      readjust the balance between opioid analgesia and side effects. The opioid switch
      resulted in more pain relief or fewer side effects in half of the patients. A
      proposed equianalgesic conversion ratio between 70:1 and 100:1 from oral slow
      release morphine to transdermal fentanyl can be confirmed by our data. Conversion
      rates from other opioids to transdermal fentanyl are suggested.

PMID- 12799930
TI  - [Medical expertise in pain therapy].

PMID- 12799929
TI  - [Headache caused by polycythemia vera. Classification of a headache under the
      heading of metabolic disturbances].
AB  - As polycythemia vera is a myeloproliferative syndrome, it is based on an
      autonomic increase in the proliferation of all hematopoetic cells--mostly of
      erythropoesis. An increase in blood viscosity induces disturbed microcirculation,
      resulting in headaches with clinical symptoms. So far, the headache in
      polycythemia vera has not been classified. METHODS: We would like to demonstrate
      a case of a female patient aged 58 years who had been complaining of persistent
      hemicranial right-sided headaches for the last 16 days, alternating between
      throbbing and stabbing pain as well as a retrobulbar feeling of pressure. Blood
      chemistry demonstrated pronounced changes: hemoglobin, 20,1 g/dl; hematocrit,
      58%; erythrocytes, 6,8 T/l (6,800,000/microl) leucocytes, 14,400/microl;
      thrombocytes, 543,000/microl A punch biopsy from the pelvic rim showed cell-rich
      bone marrow, demonstrating a myeloproliferative syndrome suggestive of
      polycytemia vera. RESULTS: Following hemodilution, the headache disappeared
      within 3 days following normalization of blood chemistry: hemoglobin, 14.9 g/dl;
      hematocrit, 44%; erythrocytes, 5.2 T/l (5,200,000/microl; leucocytes,
      13,100/microl. Further diagnosis of the headache by means of MRI of the head,
      extra and transcranial doppler sonography as well as MRI of the cervical spine
      did not produce findings with the exception of retrospondylophyth at C5-6. The
      patient was therefore managed on aspirin 300 mg daily and was given weekly
      isovolemic bleeding. The headaches did not recur. CONCLUSION: We diagnosed a
      headache caused by polycythemia vera and recommend classification of this
      headache under the heading of metabolic disturbances, because this classification
      meets the diagnostic criteria of the international headache classification.

PMID- 12799931
TI  - [Therapy with opioids in liver or renal failure].
AB  - In patients with renal or hepatic failure, the pharmacokinetics of opioids may be
      affected in several ways, leading to the necessity to correct the dose. The liver
      is the major site for biotransformation of most opioids. The major metabolic
      pathway is oxidation. Exceptions to this are morphine and buprenorphine, which
      undergo primarily glucuronidation, and remifentanil which is cleared by esther
      hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys
      and may accumulate in patients with renal insufficiency. Some metabolites such as
      morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With
      high concentrations they may cause narcotic effects or respiratory depression. In
      addition, special risks are known for normepridine that has been shown to exert
      neurotoxic effects with the risk of seizures. Few cases of respiratory depression
      following the administration of codeine, dihydrocodeine and tramdol have been
      reported. The elimination half-life of these drugs was prolonged. Lastly, the
      disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil
      appears to be unaffected in renal failure. In patients with hepatic cirrhosis it
      has been shown that oxidation of opioids is reduced, resulting in a decreased
      drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil)
      and increased oral bioavailability due to reduced first-pass metabolism
      (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation
      is thought to be less affected in liver cirrhosis, the clearance of morphine was
      found to be decreased and its oral bioavailability increased. The consequence of
      reduced drug metabolism is the risk of accumulation in the body, especially with
      repeated administrations. As for patients with renal failure, special risks are
      known for meperidine with potential accumulation of normeperidine, which can
      cause seizures, and for propoxyphene for which several cases of hepatotoxicity
      have been reported. On the other hand, the analgesic activity of codeine and
      tilidine depends on transformation into the active metabolites, morphine and
      nortilidine. In the case of reduced metabolism in chronic liver disease, the
      analgesic action of these drugs may be compromised. Lastly, the disposition of a
      few opioids, such as fentanyl, sufentanil, and remifentanil, appears to be
      unaffected in liver disease.

PMID- 12799932
TI  - [Migraine costs and success of non-medicamentous therapy procedures. Relation of
      diagnostic measures].
AB  - BACKGROUND: Migraine is a common neurological disorder (16% women, 6% men)
      associated with high direct and indirect costs. We evaluated the diagnostic and
      paramedical therapeutic measures by estimating the expenditure per patient and
      the effect of treatment. METHODS: A questionnaire was sent to 1000 patients
      attending the Essen outpatient headache centre in 1995. A total of 293 patients
      responded, of whom 165 were eligible and could be evaluated. Patients were asked
      to report diagnostic tests, paramedical treatments applied, average duration of
      success (defined as meaningful reduction in migraine frequency) and costs of
      paramedical therapy. RESULTS: Paramedical methods of therapy most frequently used
      were acupuncture, special pads, relaxation methods and herbal therapy. A total of
      579 (3.5 on average) diagnostic procedures such as brain or cervical spine CT and
      MRI or EEG was performed. The average cost for acupuncture was 465 US dollars,
      while the success was maintained for 3.2 months. 1510 US dollars was spent on
      psychotherapy, which was successful for 1.7 months. Patients spent 93 US dollars
      for relaxation methods, achieving migraine relief for 7.4 months. CONCLUSION:
      Paramedical treatments lack scientific proof, while both acute and prophylactic
      treatment strategies have been successfully tested in many clinical trials.
      Paramedical treatment shows a good temporally effect in individual patients.

PMID- 12799933
TI  - [Coenesthesia--an important differential diagnosis in chronic pain syndromes].
AB  - BACKGROUND: Coenesthesias can be defined as disorders of body perception or body
      hallucinations, projected in different parts of the body. Patients complain of
      intractable pain or dysesthesia. These symptoms are reported even from organs
      where we usually have no perception. Coenesthesia must be regarded as a symptom
      that can be observed in various psychiatric diseases, e.g., schizophrenia.
      However, in rare cases coenesthesias can be documented in neurological diseases,
      e.g., intracranial tumors or infections. Therefore, accurate assessment of
      possible differential diagnoses is important. In late stages, coenesthesias can
      easily be recognized because of their "bizarre" character. In early stages,
      however, patients often complain of intractable, unlocalizable burning pain. They
      frequently undergo operations because of their great suffering. The drug
      treatment of first choice is neuroleptics, but the results are unpredictable.
      CASES AND THERAPY: The case studies of three patients are presented and discussed
      (patient 1 with coenaesthetic schizophrenia, patient 2 with coenesthesia in the
      course of a delusional (paranoid) disorder; patient 3 with coenesthesia caused by
      carcinomatous meningitis).

PMID- 12799934
TI  - [Associations between back pain, quality of sleep and quality of mattresses.
      Double-blind pilot study with hotel guests].
AB  - BACKGROUND: Associations between back pain, the quality of sleep and the quality
      of mattress have not yet been investigated systematically. METHODS: At check-out
      we asked 265 consecutive guests of a trade fair hotel about the subjective
      quality of sleep in the previous night. Nine rooms had been equipped with new
      mattresses of three different qualities and prices, but this was kept blind to
      the hotel staff and the guests. Sleep quality was assessed on an analog scale
      between 1 (very good) and 5 (very bad) and was analyzed in comparison to the
      remaining 8-year old mattresses of the hotel, but also with respect to social
      (e.g. private vs. professional reason for the stay) as well as personal (e.g.
      previous experience with low back and sleep complaints) characteristics of the
      guests. RESULTS: The three qualities of the mattresses correlated significantly
      and positively with the perceived quality of sleep, but the difference to the
      "old" mattresses was most pronounced for those guests who were staying overnight
      for professional reasons, or who frequently were suffering from low back pain or
      sleep disturbances. CONCLUSION: At least for chronic sufferers from back pain and
      sleep problems, the association between sleep quality and quality of the mattress
      is significant.

PMID- 12799935
TI  - [Pain therapy in pediatric oncology. Qualitatssicherungsgruppe der Gesellschaft
      fur Padiatrische Onkologie und Hamatologie].

PMID- 12799936
TI  - [Practice of pain control in paediatric oncology--recommendations of the quality
      monitoring group of the German Society for Paediatric Oncology and Haematology
      (GPOH)].
AB  - In paediatric oncology, optimal pain control is still a challenge.A structured
      pain history and the regular scoring of pain intensity using age-adapted
      measuring tools are hallmarks of optimal pain control. Psychological measures are
      as important as drug therapy in prophylaxis or control of pain, especially when
      performing invasive procedures. Pain control is oriented on the WHO analgesic
      ladder. On no account the paediatric patient should have to climb up the
      'analgesic ladder'- strong pain requires the primary use of strong drugs. Opioids
      should be given by the oral route and by the clock - short acting opioids should
      be used to treat break-through pain. Alternatives are IV infusion and patient
      controlled analgesia. Constipation is the adverse effect most often seen with
      (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic
      treatment should be given consistently. The assistance of paediatric nurses is of
      utmost importance in paediatric pain control. Nurses' deliver the basis for
      rational and effective pain control by scoring pain intensity and documenting
      drug administration as well as adverse effects. The nurses task is also to
      prepare the patient for and monitor the patient during painful procedures. It is
      the responsibility of both nurse and doctor to guarantee emergency intervention
      during sedation whenever needed. In our paper we comment on drug selection and
      dosage, pain measurement tools, and documentation tools for the purpose of pain
      control. Those tools may be easily integrated into daily routine.

PMID- 12799937
TI  - [60 years of migraine research. Retrospective review and synopsis].
AB  - At the end of the thirties, the first papers from Wolff and Graham represented
      the beginning of modern migraine research. Since that time advance is important.
      Several medical disciplines and special fields in research such as neurology,
      clinical and experimental neurophysiology, neuroradiology, psychiatry, medical
      psychology, psychosomatics, biochemistry, genetics, pharmacology, epidemiology
      contributed to the new cognitions. Further exploration of genetics and of the
      interictal neuronal and neurovascular dysfunctions are the key for both
      understanding of migraine as disease and pathogenesis of migraine attacks. All
      together migraine may be defined as a specific dysfunction in neuronal
      information processing and neurovascular reagibility corresponding with imbalance
      of certain neurotransmitters (NA, 5-HT) and leading to ictal reactions of brain
      areas and intracranial vessels in critical phases of hyperreagibility and
      hyperactivity. In the pathogenetical and pathophysiological processing both
      genetic and acquired mechanisms might be involved. Aura symptoms result from
      abnormal vasoconstriction with oligemia or ischemia of the tissue as Wolff
      supposed it. The headache phase follows with delay because the pain inducing
      neurogenic inflammation in the vessel walls need more time for clinical
      manifestation than the oligemic resp. ischemic brain symptoms.

PMID- 12799938
TI  - [Information of patients in complementary medicine: acupuncture].
AB  - Complementary medicine is not a therapy without side effects. Undergoing
      acupuncture can result in hazardous complications. Therefore patients should be
      advised of adverse events associated with acupuncture. A consent form for
      acupuncture is presented. Only physicians with good anatomical and clinical
      skills should use acupuncture.

PMID- 12799939
TI  - [Structure quality in outpatient care of chronic pain patients].
AB  - BACKGROUND: Outcome quality of medical treatment depends on structure quality of
      the treatment facility. In the present study we tried evaluate structural
      parameters of outpatient treatment facilities relating to management of headache,
      low back pain and cancer pain. METHODS: 109 outpatient treatment facilities (104
      offices, 3 outpatient departments of hospitals, 2 pain ambulances of hospitals)
      in middle franconia, one of the larger Bavarian administrative division
      (population: 1,6 Mio.), have been evaluated by questionnaires. Questions examined
      certain structural conditions of the treatment facility as compared to german
      guidelines for outpatient treatment of pain patients
      ("Schmerztherapievereinbarung"). RESULTS: Only one treatment facility worked
      within an interdisciplinary setting. Less than 25% (median) of total patients of
      an outpatient treatment facility suffered from acute or chronic headache, low
      back pain or cancer pain. 38% of physicians participated regularly on pain
      conferences. Established methods for diagnosis and documentation of patients
      suffering from chronic headache, chronic back pain and cancer pain were regularly
      used by 16%, 12% and 10% of physicians, respectively. Regular interdisciplinary
      cooperation in the management of patients with chronic headache, chronic back
      pain and cancer pain was indicated by 28%, 24% and 41% of physicians,
      respectively. However, personal discussion of patient related problems took place
      in less than 5% of physicians. Although a considerable number of different
      therapies (included as standard therapy for outpatient management of chronic pain
      in the "Schmerztherapievereinbarung") can be applied in each outpatient treatment
      facility (median:5), psychological therapy for management of chronic headache,
      chronic back pain and cancer pain was used regularly by 5%, 2% and 7% of
      physicians, respectively. Scoring of all examined structural parameters provides
      a measure for the quality of the parameters of a certain outpatient treatment
      facility as compared to that of an optimal outpatient facility for pain treatment
      (quality score=100%). However, 75% of examined outpatient treatment facilities
      reached quality scores only up to 43%. CONCLUSIONS: There are considerable
      structural deficits in outpatient treatment facilities involved in management of
      patients suffering from chronic headache, chronic back pain and cancer pain.
      Realisation of standards according to the "Schmerztherapievereinbarung" needs
      organisation of an interdisciplinary network between the different specialties
      necessary for pain management. Interdisciplinary cooperation should be supported
      by the official organization of the medical self-government in Germany--the
      Kassenarztliche Vereinigung--which has to assure optimal conditions for
      outpatient treatments.

PMID- 12799940
TI  - [Peripheral nerve stimulation for pain relief in CRPS II and phantom-limb pain].
AB  - OBJECTIVES: We performed 52 peripheral nerve stimulation procedures since 1991.
      In addition to 48 patients with CRPS II, 4 patients with phantom-limb pain were
      treated. Incomplete or complete lesion of the stimulated peripheral nerves was
      determined in all patients. Surgically treatment failed in all cases. All
      patients had been given extensive conservative pain therapy. MATERIAL AND METHOD:
      The aim was to define a standardised method, which would be as objective as
      possible, to verify the success of treatment, by measuring the pain-related
      disability assessment, the subjective intensity of pain and the subjective
      perception of pain. Long-term follow-up was arranged in addition to determine
      social and occupational re-integration. The implantation of the stimulating
      electrode, proximal to the lesion, was performed after microsurgical neurolysis
      of the peripheral nerves. The patient carried out a stimulation trial after the
      operation. At the conclusion of the trial stimulation phase, a stimulator unit
      was permanently implanted in 47 cases, with a marked reduction in pain. Only in 5
      cases, the success of the trial stimulation was unsatisfactory. RESULTS: After
      implanting the stimulator unit an average pain-related disability of 10% was
      achieved by the 47 patients fitted with a permanent implant. 43 patients have
      used the permanent stimulator implants with lasting, excellent to good success.
      The stimulator system was removed in only 4 cases, due to the need for
      stimulation having passed, or due to a lack of lasting success with stimulation.
      CONCLUSION: Neurostimulation of peripheral nerves should be considered as an
      established concept to treat surgically failed peripheral nerve lesions.

PMID- 12799941
TI  - [In vitro investigations of the effect of morphine and its metabolites on the
      phagocytosis of peripheral mononuclear cells].
AB  - INTRODUCTION: Reports about an increased incidence of infection with facultative
      intracellular microorganisms suggest a depression of the macrophage/monocyte
      system. This explosive increase in oxidative metabolism can be measured by
      chemiluminescence. The aim of the present study was to investigate the influence
      of morphine and its metabolites morphine-3 (M-3-G) and 6-glucuronide (M-6-G) on
      the respiratory burst of the peripheral mononuclear cells (PCM). To explain the
      mechanism of the effect of morphine the antagonist naloxone was used.
      Furthermore, the effect was compared with that of bupivacaine and propranolol,
      known as drugs that stabilize the cell membranes. METHODS: PMC were isolated from
      the blood of healthy young men by Ficol hypaque centrifugation. Four samples of 2
      x 10(5) cells were incubated for at 37 degrees C and 10% CO(2) with either
      morphine, naloxone, bupivacaine, propranolol, M-3-G or M-6-G. After stimulation
      with oponised zymosan A, the lucigenin-dependent chemiluminescence was measured
      (n=8) in a biolumat (Berthold). STATISTICS: Wilcoxon matched pairs (significance
      level p<0.05). RESULTS: Morphine inhibited the phagocytic activity of PMC only in
      concentrations >10(-7) mol/l. The metabolites M-3-G and M-6-G were considered to
      be similar based on tests using n=3. Naloxone itself significantly influences the
      emission of light solely in the high concentration of 10(-4) mol/l. Naloxone (10(
      4) mol/l)+morphine(10(-5) mol/l) caused a greater inhibition than either of the
      substances alone. In comparison, the decreased chemiluminescence of morphine (10(
      6) mol/l) was antagonized by naloxone (10(-5) mol/l). Naloxone in the same
      concentration was ineffective. The membrane stabilization caused by bupivacaine
      and propranolol did not change the chemiluminescence activity. CONCLUSION:
      Morphine had a decreasing effect on the respiratory burst of PCM only in
      concentrations that the human body reaches where renal clearance is reduced. In
      this situation the metabolites of morphine accumulate more than morphine itself
      and seem to have a similar effect. The weakening of phagocytosis might possibly
      be a direct effect of morphine and its metabolites. These investigations suggest
      that this phenomenon may be receptor dependent: the effect could be antagonized
      by naloxone, but naloxone itself caused a depression in high concentrations. In
      comparison the nonspecific stabilization of the membranes showed no such effect.

PMID- 12799942
TI  - [Pain therapy near the spinal marrow. Status survey in Germany and Austria].
AB  - OBJECTIVE: The objective of this survey was to investigate the current status of
      the epidural and intrathecal management in patients with chronic cancer and non
      cancer pain in Germany and Austria. METHODS: In June 1997 a questionnaire was
      sent to 598 German and Austrian anaesthesiologists specialized in pain therapy.
      Questions concerning the use of medicaments for epidural and intrathecal
      treatment of chronic pain were asked. RESULTS: The response rate was 23%. The
      data show that 78% of the anaesthesiologists use epidural or intrathecal
      analgesia in the therapy of chronic pain. Local anaesthetics are used by 85% of
      these anaesthesiologists, followed by morphine (72%), clonidine (48%),
      buprenorphine (34%), baclofen (20%), fentanyl (13%) and sufentanil (10%). For
      most of the treatments local anaesthetics are used, again followed by opioids und
      clonidine. In the 137 answering pain clinics 79.821 epidural and intrathecal
      analgetic treatments are performed per year. DISCUSSION: Epidural and intrathecal
      pain therapy is frequently used in Germany and Austria, either as a complementary
      or alternative treatment to systemic pain therapy. Local anaesthetics followed by
      opioids are the most commonly used medicaments for this treatment. For some of
      the applied substances neurotoxicological data are lacking. The use of these
      substances has to be considered very carefully.

PMID- 12799943
TI  - [Value of "medication screening" in therapy for chronic pain].
AB  - INTRODUCTION: Drug therapy plays often an important role in the treatment of
      chronic pain. Former studies and also experiences of clinical practice have given
      evidence, that insufficient patient compliance is a widespread event. Therefore
      drug screening becomes a significant tool for quality assurance. In the following
      the methodical and practical aspects of drug screening are described and
      recommendations for its use in clinical practice are suggested. OBJECTIVE OF DRUG
      SCREENING: This tool can be used to check the intake of prescribed drugs, to
      detect hidden taken drugs, to decide whether side effects result of the
      prescribed medication or not and to support a withdrawal therapy. PRACTICAL
      BASICS AND INTERPRETATION OF THE FINDINGS: Drug screening presupposes an informed
      patient, who consents to the investigation. Otherwise confidence is risked and
      the handling with unexpected results is not possible any more. Testing of urine
      has the advantage of a non invasive procedure and makes use of the reservoir of
      the bladder. A close co-operation and good communication between therapist and
      laboratory prevents misinterpretations, which might result from inaccurate
      formulated questions or methodical limitations, for instance because of cross
      reacting substances or a too insensitive detection level for the respective drug.
      The finding must primary bee used to value the therapy and improve the compliance
      but can not prove the patient himself. CONCLUSIONS: Even if the value of drug
      screening is not prospectively investigated until now, clinical experiences
      reveals it is as powerful tool for monitoring effectiveness and side effects of
      pharmacotherapy of pain and also of patient compliance which the prescribed drug
      regimes.

PMID- 12799944
TI  - [Headaches associated with diseases of skull and neck].

PMID- 12799945
TI  - [Neurobiological basis of muscle pain].
AB  - MECHANISMS IN THE LESIONED MUSCLE: The peripheral mechanism underlying the
      tenderness and pain during movement of a damaged muscle is the sensitization of
      muscle nociceptors. Ongoing activity of nociceptors causes spontaneous pain in
      addition to tenderness. Muscle pain (particularly that originating in myofascial
      trigger points) is often mislocalized because it is referred to other deep
      somatic tissues. The development of trigger points is a purely peripheral event,
      whereas the referral of muscle pain is based on central nervous mechanisms.
      MECHANISMS AT THE SPINAL LEVEL: The input from muscle nociceptors induces
      neuroplastic changes in the spinal cord and higher centres of the central nervous
      system. These changes are associated with an overexcitability of neurones
      (central sensitization) and contribute to hyperalgesia of patients. Resting
      activity of spinal neurones (and hence spontaneous pain) is strongly dependent on
      nitric oxide (NO). A muscle lesion is likely to lead to an inhibition of the
      homonymous muscle, it can, however, elicit spasm in another muscle. SUPRASPINAL
      MECHANISMS: Spinal neurones that mediate muscle pain are subjected to a strong
      descending inhibitory influence. The inhibitory tracts originate in the
      mesencephalon and medulla oblongata. A dysfunction of this inhibitory system
      might be involved in the pathogenesis of fibromyalgia.

PMID- 12799946
TI  - [Coping and convalescence course after lumbar disk operations].
AB  - BACKGROUND: Aim of the present prospective longitudinal study was the statistical
      foundation and thus further replication of recent findings of Hasenbring [13],
      who postulated a significant importance of specific, within the psychological
      pain research long neglected pain coping strategies as risk factors concerning
      pain chronification: appeals to "stick it out" on the cognitive level and
      endurance strategies on the behavioural level. METHODS: In contrast to
      Hasenbring's heterogeneous chronic pain patients sample (first plus repeated
      surgical or conservative treatment) the present 82 low back pain patients with
      acute radicular pain and simultaneous lumbar disc prolapse all underwent first
      time lumbar nucleotomy. Prior to treatment we conducted an extensive
      psychological and neurological examination. The psychological tests included a
      general depression scale (Allgemeine Depressionsskala; ADS) and the Kiel Pain
      Inventory (KPI). Based on these scales a cluster analysis was performed, which
      allocated patients to four distinct groups resembling the group structure
      ascertained by Hasenbring [12, 13]: A first group of patients characterized by a
      positive mood and marked endurance strategies (n=7); another cluster with
      depressive mood and simultaneous cognitive appeals to stick it out (n=10); a
      third group of emotionally depressed patients who preferably applied social and
      physical avoidance strategies in their coping with chronic pain (n=29), plus a
      last cluster without any psychological risk factors (n=26). RESULTS: As treatment
      outcome criteria to evaluate the quality of the convalescence process six months
      later we assessed the pain intensity (11-point self-rating scale), the ability to
      work, and whether the patients had applied for early retirement or not. Results
      showed no significant differences in pain intensity between the groups at the 6
      month follow up. Concerning the two other outcome variables the two clusters
      characterized by cognitive or behavioural endurance tendencies turned out to be
      high risk groups: At the 6-month follow up patients of both groups seemed less
      likely to return to work. The patients typified by endurance strategies and
      positive mood had more often applied for early retirement than those patients
      without psychological risk factors. DISCUSSION: These results corroborate the
      finding that this subgroup of chronic low back pain patients might indeed carry a
      bad prognosis and call for further research into this area, especially with
      regard to rehabilitation potential and facilities of reintegration into working
      life.

PMID- 12799947
TI  - [The specific cognitive stile of pain patients supports chronification of pain].
AB  - BACKGROUND: In a cognitive perspective, chronic pain comprises at least three
      dimensions: First it is possible to study the relevance of pain related
      attitudes, beliefs and coping cognitions for the chronification of pain. Second
      psychological processes of learning and memory processes can be analysed. Third
      we can investigate uncontrolled cognitions in chronic pain patients. AIM OF THE
      STUDY: The first part of the present paper deals with representations of pain
      events in autobiographical memory. In the second part a hindsight bias experiment
      is used as a prototype of altered information processing in the context of
      chronic pain. STUDY 1: In study one recollection of pain related events, pain
      experience and the sensory recalling of pain occurrences were sampled in 20
      chronic pain patients, 17 psychiatric patients and 38 healthy controls. Pain
      patients showed a specific kind of pain related memory which had no parallel
      among psychiatric patients. Based on learning theory the significance of a pain
      related memory for chronification is discussed. STUDY 2: In the second study 18
      pain patients, 13 psychiatric patients and 18 healthy controls were tested with a
      hindsight bias experiment. The hindsight-effect was observed in the usual extend
      in the student control group, but was significantly greater in the pain group and
      absent in the psychiatric sample. In addition to this global finding, multinomial
      modeling revealed group differences in specific model parameters. Basic units of
      information processing interact with the chronification of pain. This method of
      analysis thus proved as a promising tool for the assessment of cognitive aspects
      of clinical disorders.

PMID- 12799948
TI  - [Pharmacist's attitudes towards opioid prescription].
AB  - The prescription of strong opioids underlies a special legislation. The attitude
      of the pharmacists towards the long-term treatment with these analgesics and
      their opinion about the legislation is unknown in Germany and other European
      countries. METHODS: A questionnaire was included in the Journal "Mitteilungsblatt
      der Apothekerkammer Westfalen-Lippe" and send to all 2300 pharmacists of the
      region Westfalen-Lippe in December 1997. RESULTS: 797 (35%) questionnaires were
      returned. In 82.4% of the pharmacies strong opioids are kept in stock. However,
      140 pharmacists do not have opioids in stock due to too many different
      preparations or low prescription rate. 54% of the pharmacists warn their patients
      about endangering by the medication. The fear of psychological addiction (48.1%)
      is the main argument, also in patients with regular intake of the opioids (20.1%)
      and related to long acting opioids (10.8%). Nevertheless, 73% of the pharmacists
      advocate for a liberalization and 10.7% for an abolishment of the actual
      prescription laws. DISCUSSION: The importance of the therapy with strong opioids
      is well accepted by the pharmacists. An ease of the prescription is demanded to
      improve the situation of the patients with chronic pain. However, the majority of
      the pharmacists warns the patients about this medication. Contact between
      prescribing doctors and pharmacists and an intensified education concerning the
      therapy with opioids are needed in addition to the education of the medical staff
      and the liberalization of the prescription laws.

PMID- 12799949
TI  - [Migraine with aura as early symptom of neurosyphilis].
AB  - CASE: On the basis of a case report the often difficult classification of
      migraine with aura and exclusion of symptomatic origin is discussed. In spring
      1996 a 34-years old patient started to suffer from attacks of a migraine like
      headache with focal aura several times a week. While clinical examination was
      inconspicuous the electroencephalogram showed a general slowing of background
      activity with intermittent rhythmic delta-activity. NMR was normal. During
      treatment with flunarizine intensity and frequency of the attacks decreased, but
      within half a year he developed an increasing psychomotor slowing and cognitive
      deficit. Now cerebrospinal fluid showed a pleocytosis and highly positive
      treponema pallidum specific antibody index making the diagnosis of neurosyphilis
      reliable. Parenteral penicillin caused a delayed normalisation of mental
      abilities and CSF. DISCUSSION: Headache, especially with the characteristics of
      migraine, is one of the most frequent symptoms of neurosyphilis and--if untreated
      -may be followed by transient ischemic attacks or strokes even month later. To
      detect this kind of symptomatic headache a careful neurological follow-up
      examination and early CSF-analysis are essentially necessary, because
      pathological electroencephalograms are not rare in migraine with aura and NMR
      cannot exclude an inflammatory process.

PMID- 12799950
TI  - [Prophylaxis and treatment of drug-induced persistent headache. Therapy
      recommendation of the German Society for Migraine and Headache].

PMID- 12799951
TI  - [2-Arylpropionic acids. Role in pain therapy].
AB  - The antipyretic analgesics still comprise the most widely used group of analgesic
      compounds. Until twenty years ago, aspirin, phenazone derivatives and
      acetaminophen had been used as standard remedies for intercurrent harmless pain
      conditions in connection with infections, trauma, small surgeries, but also for
      tension headache and other painful conditions. During the last decades, this
      group has been supplemented by a variety of 2-arylpropionic acids being primarily
      developed for the treatment of rheumatic pain and inflammation. Some of them
      (e.g. ibuprofen, ketoprofen and naproxen) have been given over-the-counter status
      in some countries because of their relative safety at low doses. Nevertheless,
      pharmacodynamic and pharmacokinetic differences among the various substances of
      this group make them suitable to a different degree for the treatment of pain
      conditions.

PMID- 12799952
TI  - [Sleeping behavior and migraine. An evaluation by daily self-reports].
AB  - PROBLEM: Regarding the coherence of sleeping behavior and the occurrence of
      migraine attacks, we conducted a study based on migraine and sleeping diaries.
      METHODS: Besides the daily recording of times of falling asleep and waking up,
      duration of sleep, sleep disruption and quality of sleep, clinical migraine
      parameters like occurrence of migraine attacks, headache intensity and duration
      and the daily mood rating were registered over periods of at least 6 weeks. In
      the analyses, we defined two classes of events: (1) nights not followed by a
      migraine attack; (2) nights followed by migraine. We examined a retrospective
      sample (23 patients with altogether 580 attacks) and a prospective sample (16
      patients with altogether 96 attacks). RESULTS: In both samples, we found that the
      duration of sleep was significantly reduced in nights followed by migraine (6.8
      vs. 8.1 h and 6.4 vs. 7.2 h respectively) due to earlier awakening, with
      unchanged time of falling asleep. Up to two thirds of the observed migraine
      attacks were reported to be present directly after awakening. Quality of sleep
      was markedly reduced in nights followed by a migraine attack (i.e. sleep
      disruptions, feeling exhausted/no feeling of restedness when wakening up). We
      found only weak and insignificant correlations between the foregoing daily mood
      rating and the quantitative parameters of sleeping behavior on nights followed by
      migraine; somewhat more pronounced correlations were observable between the mood
      rating and the qualitative sleep parameters. CONCLUSIONS: Overall, we conclude
      that the observed changes in sleeping behavior are largely part of the migraine
      attack, with the possibility that REM sleep functions as a migraine trigger. In
      clinical application, we strongly recommend the use of daily self-observations of
      patients' sleep-related behaviors in the migraine diary, identifying migraine
      prone sleeping habits and evaluating their potency for triggering migraine
      attacks.

PMID- 12799953
TI  - [Ketorolac and butylscopolamine in combination with alfentanil for renal
      lithotripsy].
AB  - BACKGROUND: Patient-controlled analgesia (PCA) using intravenous alfentanil
      provides adequate pain relief during extracorporal shock wave lithotripsy (ESWL)
      of renal stones. Occasional disadvantages of opioid analgesia include nausea,
      sedation and respiratory depression. This double-blind, placebo-controlled study
      examined whether the alfentanil requirements and thereby the frequency of side
      effects could be reduced by preemptive analgesia with the non-opioid analgesic
      ketorolac or the spasmolytic butylscopolamine. METHODS: 90 patients scheduled for
      ESWL of renal stones received 1 hour prior to ESWL ketorolac 30 mg,
      butylscopolamine 20 mg or placebo intramusculary. 10 mg of metoclopramide and 6.6
      microg/kg of alfentanil were given intravenously at the beginning of ESWL
      (Philips/Dornier MFL 5000). Intravenous PCA was started (demand dose: 0.25 mg of
      alfentanil, lockout time: 1 minute). Pain intensity (NRS 0-100), sedation score
      (VRS 0-4), respiratory rate (min(-1)) and partial oxygen saturation (SO(2)) were
      measured every 5 minutes. Statistical analysis included ANOVA and Chi-square-test
      (p<0,05). RESULTS: Demographic and ESWL data were comparable between the study
      groups. However, patients of the ketorolac group were statistically significantly
      younger than those in the other groups. Alfentanil doses, pain scores and
      frequency of respiratory depression, sedation and nausea were lower subsequent to
      ketorolac than subsequent to butylscopolamine or placebo (not statistically
      significant). Signs of respiratory depression were only seen during ESWL.
      CONCLUSIONS: The present study confirms that PCA using alfentanil is effective
      during ESWL of renal stones. However, because of the possibility of respiratory
      depression, adequate monitoring is mandatory. Preemptive analgesia with 30 mg of
      ketorolac or 20 mg of butylscopolamine cannot reduce alfentanil requirements or
      improve efficacy and safety.

PMID- 12799954
TI  - [Discrimination between pain-induced head movement disturbances after whiplash
      injuries and their simulation].
AB  - Neck pain after whiplash injury of the cervical spine often induces typical
      changes in head motion patterns (amplitude, velocity). These changes of
      kinematics may help to recognize malingerers. We investigated the hypothesis that
      malingerers are not able to reproduce their simulated head movement disturbances
      three times. The kinematics of head movements of 23 patients with neck pain after
      whiplash injury and of 22 healthy subjects trying to act as malingerers were
      compared. The healthy subjects were informed about the symptomatology of whiplash
      injury and were asked to simulate painful head movements. Two different kinds of
      head movements were registered and analyzed by Cervicomotography: (1) the slow
      free axial head rotation (yaw) and (2) the axial head rotation (yaw) tracking a
      moving visual target. Each experimental condition was presented three times,
      expecting the malingerers not to be able to produce as well as to reproduce the
      same head movement disturbances again and again. In patients, as a consequence of
      their distinct pain patterns, we expected less variance between the test
      repetitions. The statistical analysis showed significant differences of the
      calculated kinematic parameters between both groups and the inability of healthy
      subjects to simulate and to reproduce convincingly distinct pain patterns.

PMID- 12799955
TI  - [Change sensitivity and construct validity of the revised multi-dimensional pain
      scale].
AB  - PROBLEM: Assessment and evaluation of perceived pain is an interdisciplinary
      task. This study focused on the change sensitivity and construct validity of the
      German version of the Revised Multidimensional Pain Scale (MSS). METHODS: In this
      experiment, 72 students were assigned to one of three treatments:a) Applying a
      blood pressure sphygmomanometry cuff with a maximum pressure of 300 mm Hg, b) or
      with a maximum pressure of 175 mm Hg, c) or a control condition, applying a cuff
      with no pressure. During the treatment, blood pressure was continuously non
      invasively measured by the Penazmethod. At the end of the experiment, the
      subjects worked on the revised multidimensional pain scale, on the state/trait
      anxiety inventory (STAI) and a Likert-scale (range 1-28) for perceived pressure.
      RESULTS: As expected, inflating the arm cuff induced a significant increase in
      pressure perception compared to the control group. However, only the subscales
      electrical and thermic of the MSS showed an increase across the treatment groups.
      No differences were found for the anxiety ratings. Correlation analysis showed
      that state anxiety was positively related with the subscales chronic, chemical,
      and thermic. Trait anxiety was related with the subscales chronic, inconvenient,
      and chemical. Systolic blood pressure increase was positively correlated with the
      subscale general of the MSS. DISCUSSION: The study shows that the MSS has a
      limited change sensitivity for short term pain stimuli like arm cuff pressure.
      Anxiety was correlated with three subscales of the MSS, indicating that perceived
      pain intensity assessed with the MSS is more related to emotional factors rather
      to the physical intensity of the arm cuff pressure.

PMID- 12799956
TI  - [Dental trigeminal neuralgia].
AB  - INTRODUCTION: Although the majority of patients with recurrent hyperalgesia of
      the nervus trigeminus may benefit from drug treatment or invasive
      (thermocoagulation) and other surgical interventions, a minority of patients does
      not respond to these strategies. Hence, unusual etiologies must be taken into
      consideration. CASE REPORT: Mrs F., a 74-year-old women suffered from acute left
      side trigeminalgia ten days after receiving a new dental prosthesis (upper jaw).
      Intensive pain attacks occurred spontaneously when she was speaking and could
      also be evoked by gentle exogenous pressure at the upper lip. INTERVENTION: The
      painful area has been identified by careful clinical evaluation. Local
      administration of antibiotics combined with laser coagulation successfully cured
      the trigeminalgia after 4 weeks which did not recur in the follow-up period over
      2 months. CONCLUSION: Since patients longer history revealed pain attacks of
      minor severity we suggest that local inflammation at the gingiva might have
      stimulated quiescent nociceptors over time. The local pressure to this area
      evoked by the new prosthesis seems to be definitive trigger factor to intensify
      the nociceptor response resulting in higher number of trigeminalgia attacks of
      marked severity. We therefore conclude that differential diagnosis of symptomatic
      trigeminalgia should include dental gingival mechanisms at least in a case
      exhibiting resistances to other treatment.

PMID- 12799957
TI  - [Therapy and prophylaxis of face neuralgia and chronic pain of other origin].

PMID- 12799958
TI  - [The languages of pains].
AB  - The plural words "languages" and "pains" emphasize the variety of the conditions
      and the locations from which pain emerges of the conduction and processing of
      pain stimuli in the central nervous system, and of the subjective gestalt of pain
      feeling. The personal expression in speaking, facial expression, gestures, and
      posture is, like words, a mixture of measurable and understandable elements. The
      verb "to hurt" should therefore be understood and used transitively and
      intransitively, passively and actively by suffering and by acting-forming. The
      concept--called isopathy--of the analysis of the conditions of possible
      understanding of the affective expressions of a person by an empathic
      participating observer and listener should be applied to the understanding of
      pains in one individual person.

PMID- 12799959
TI  - [Treatment of pain and information of patient].
AB  - Treatment of pain is an medical operation that requires informed consent of the
      patient as justification. Invasive treatment of pain causes frequently civil and
      sometimes even criminal responsibility of the physician which can be reduced by
      detailed information about typical risks. Information about abuse, physical and
      psychological dependence and consequences on the ability to operate a vehicle
      must be a part of a medicinal treatment. In any treatment, the patient has a
      right to information about serious alternative methods. It is the responsibility
      of the physician to inform the patient in a personal dialogue. Information forms
      can support but not replace the dialogue. In case of minority of the patient or
      missing expression of will the physician has to inform the legal
      representative(s) or to search for the presumed will of the patient. The
      information about post operative treatment should take place before the operation
      to keep the patients consent free of influence of anesthesia or pain caused by
      the operation. Treatment of pain is often not vital and additional to treatment
      of the basic disease, so that the physician has to inform both about the
      treatment of pain and of basic disease. Even by final disease a renunciation of
      information is possible only under very restricted circumstances. Documentation
      has to be a part of any information to avoid lack of evidence in a trial.

PMID- 12799960
TI  - [Intraepidermal free nerve fiber endings and their importance for cutaneous
      pain].
AB  - INTRODUCTION: Former studies performed by means of supravital methylene blue (MB)
      staining could demonstrate intraepidermal free nerve fiber endings (FNE).
      Unfortunately, these publications were only illustrated by drawings. Furthermore,
      the practical details of the method were only insufficiently handed down to
      posterity. Therefore, a modification of the staining procedure should be worked
      out for this purpose. Subsequently, the possible advantages of the method
      compared with common histochemical techniques should be clarified. Regarding the
      possible nociceptive functions of the FNE, the corresponding conclusions should
      be drawn from the results. METHODS: The dye was injected subepidermally into the
      hairless skin of the palmar- and plantar sites of rat paws followed by light
      microscopy. RESULTS: 2 different morphological types of FNE could be detected
      within the epidermis. The thick FNE, which occurred less frequently than the thin
      ones (approximately 20/mm(2) in relation to 1000/mm(2)), represented nerve fiber
      branches ascending up to the granular layer where they formed superficial plexus
      (Figs. 1 and 3b). In contrast to the thick FNE, the thin ones were varicose and
      unbranched (Figs. 2 and 3a). CONCLUSIONS: Regarding the demonstration of
      morphological details, especially the branching pattern and the thickness of FNE,
      MB-staining achieves interesting results. The visualization of 2 different types
      of FNE within the epidermis extends the validity of the concept of punctate
      sensibility into this skin layer. Both types of FNE have to be functionally
      connected with different sensoric tasks. Possibly, a subpopulation of the thin
      FNE might be identical to the substance P-immunoreactive one which is wellknown
      to possess primarily a nociceptive function.

PMID- 12799961
TI  - [Frequency and treatment success of pain in childhood--a survey of parents].
AB  - INTRODUCTION: Pain in childhood still seems to be a major problem. In this study
      we investigated parents' opinion about the frequency of pain in their children
      and the efficacy of pain treatment. METHOD: Parents of 93 children (average age:
      11-14 years) answered a questionnaire. The participants were asked to evaluate
      the frequency of pain and the success of pain treatment in their children. They
      were also asked about their family structure. RESULTS: The result confirmed that
      perioperative pain therapy in children was not satisfactory. However, the
      majority of parents were satisfied with the outpatient pain therapy. CONCLUSION:
      In order to achieve adequate and successful pain therapy in childhood, better
      information of the parents and better medical education of doctors is mandatory.

PMID- 12799962
TI  - [Antinuclear and anticardiolipin antibodies in primary headache syndromes].
AB  - Some recent studies report on slightly increased serum levels of anticardiolipin
      IgG antibodies in patients with migraine with and without aura. METHODS: To
      confirm these results we investigated the frequency of anticardiolipin IgG and
      IgM antibodies, the anti-nuclear antibodies, and the serum complement in patients
      with migraine without aura (n=47), migraine with aura (n=10), cluster headache
      (n=12), and chronic headache of the tension type (n=31) according to the IHS
      classification and using commercially available tests. RESULTS: Compared with a
      group of healthy subjects (blood samples were taken during blood donation), the
      patients with and without migraine had slightly positive anticardiolipin IgG
      antibodies significantly more often (22.8% to 4.5%). The other headache patients
      did not exhibit an increased incidence (9.7% and 0%). Compared to the
      neurological controls (13%) there was a strong tendency towards more often
      positive titers in the migraine patients. CONCLUSION: Our finding of increased
      incidence of positive anticardiolipin IgG antibodies in migraine patients (also
      reported in other studies) raises the question if these antibodies unspecifically
      support the occurrence of a migraine attack by increasing the interaction of
      blood cells and the endothelium. Furthermore, we discuss whether the observed
      increased incidence of strokes in patients with migraine may in part be caused by
      the also increased incidence of anticardiolipin antibodies, which are an
      independent risk factor for stroke.

PMID- 12799963
TI  - [Management of posttraumatic headache after head trauma and whiplash injury].

PMID- 12799965
TI  - [Pathophysiology and diagnosis in patients with sympathetically dependent pain].
AB  - Chronic pain in a distal extremity that is accompanied by autonomic dysfunction
      in the same region is taken to indicate reflex sympathetic dystrophy. Typically,
      hyperalgesia to light touch is present in addition to the spontaneous pain. The
      absence of heat hyperalgesia indicates that the underlying mechanism is central
      rather than peripheral sensitization. This mechanism is similar to that of
      secondary hyperalgesia in the intact skin surrounding an injury site.
      Sympathetically maintained pain (SMP) is diagnosed, when these sensory symptoms
      are reversible under sympathetic blockade. SMP is not due to hyperactivity of
      sympathetic efferents but to receptor supersensitivity, probably by
      overexpression of alpha(1)-adrenergic receptors on nociceptive primary afferents.
      This way normal levels of norepinephrine can cause pathological spontaneous
      activity of nociceptors which maintains the central sensitization. Chronic
      burning pain and cutaneous hyperalgesia may also be independent of the
      sympathetic innervation of the skin. In this case, central sensitization is
      maintained by other mechanisms. A role of the sympathetic nervous system in the
      pathogenesis of pain cannot be deduced simply from the simultaneous presence of
      sensory and autonomic clinical signs and symptoms. Therefore, sympathetic
      blockade in a patient initially is a diagnostic procedure, aiming to demonstrate
      the presence of the symptom SMP. Therapeutic blockade is only indicated after
      this demonstration. For the substantial number of patients with sympathetically
      independent pain, other treatment modalities are needed which may for example
      attack central sensitization.

PMID- 12799966
TI  - [Sympathetic nervous system and pain: pathophysiological mechanisms].
AB  - Sympathetic postganglionic neurons may be involved in the generation of pain,
      hyperalgesia and neurogenic inflammation under pathophysiological conditions.
      Experiments on animal models show that two categories of influence of the
      sympathetic neuron on afferent neurons can be distinguished and this distinction
      seems to be related as to whether sympathetic-afferent coupling develops after
      nerve lesion or after tissue trauma with inflammation. (1) Peripheral nerve
      lesion generates plastic changes of the afferent and sympathetic postganglionic
      neurons. This may lead to chemical coupling between sympathetic and afferent
      neurons which may entail activation and/or sensitization of primary afferent
      neurons by the sympathetic neurons. The mediator is probably noradrenaline and
      the afferent neuron expresses or upregulates functional adrenoceptors. The
      coupling may occur at different sites of the primary afferent neuron, e. g., at
      the lesion site, remote from the lesion site in the dorsal root ganglion or
      between nonlesioned sympathetic and afferent neurons which show collateral
      sprouting. The biochemical signals which trigger these changes probably are
      neurotrophic substances and their receptors which are synthesized by the
      peripheral neurons, Schwann cells and other cells in response to the peripheral
      lesions. (2) Sympathetic nerve terminals in peripheral tissues may serve as
      mediator elements in hyperalgesia and during inflammation following tissue trauma
      without nerve lesion. This function is largely independent of activity in the
      sympathetic neurons and independent of vesicular release of transmitter
      substances. The signals are probably synthesized and released from the
      sympathetic terminal or in association with it and belong to the prostaglandins
      (probably PGE(2) or PGI(2)). Furthermore, nerve growth factor (NGF) has a
      hyperalgesic action in inflammation which is at least in part dependent on the
      sympathetic nervous system.

PMID- 12799967
TI  - [The relation between sympathetically maintained pain, regional vasomotor
      disturbances and sympathetic nerve activity: a remaining enigma].
AB  - In simultaneous bilateral nerve recordings, patients with Sympathetically
      Maintained Pain (SMP) affecting one limb show similar sympathetic traffic in
      nerves supplying the affected and unaffected limb, also when the painful limb
      shows a marked regional autonomic (vasomotor) dysfunction. These findings argue
      against the notion that SMP must be mediated by a reflex change in the pattern of
      sympathetic discharge. In general, they underline the fact that autonomic
      effector disturbances may give little information about underlying nerve traffic.

PMID- 12799968
TI  - [Sympathetic nervous system and pain--some open questions].
AB  - BACKGROUND: Neuropathic pain syndromes may be treated by intervention at the
      sympathetic nervous system. The pain in these syndromes is therefore called
      sympathetically maintained pain (SMP). Typical disorders with a SMP component are
      complex regional pain syndromes (reflex sympathetic dystrophy and causalgia),
      traumatic neuralgias and herpes zoster. RESULTS: Open questions are how the
      efferent sympathetic nervous system is capable of influencing pain sensation and
      which mechanisms underly the autonomic dysregulation often observed in these
      syndromes.(1) Somatic afferents that project through the sympathetic trunk do not
      exist. Therefore, a pure sympathetic block does not block afferent information
      arising from the affected extremity. What alternatives are possible? Under
      pathophysiological conditions a functional interaction of efferent sympathetic
      fibers and afferent nociceptive fibers could be demonstrated in patients and
      animal studies. The intensity of this coupling varies considerably between
      individual patients and is not necessary for the diagnosis of the disorder. (2)
      Sympathetically maintained pain and signs of autonomic dysfunction are
      independent clinical and pathophysiological phenomena without any causal
      relation. However, it is possible to treat both the SMP and the autonomic
      dysfunction with sympathetic blocks.

PMID- 12799969
TI  - [Diagnostic and treatment measures in patients with sympathetically maintained
      pain].
AB  - The term "sympathetically maintained pain" (SMP) describes a symptom that might
      accompany a variety of diseases (CRPS, (post-) herpetic and post-injury
      neuralgia), which might transform into sympathetically independent pain (SIP)
      after some time. Patients with SMP present a bunch of disorders of the autonomic
      and sensory system, but the only reliable way to diagnose a pain as SMP is a
      positive response to an intervention at the sympathetic nervous system. Three
      ways of influencing the sympathetic system are commonly used: (a) local
      anesthetic sympathetic blockade (SB), (b) intravenous regional sympathectomy
      (IVRS) and (c) ganglionic local opioid application (GLOA). A review of current
      literature shows that SB has certain advantages in diagnostic sensitivity,
      whereas GLOA might be slightly superior in therapy of some diseases with
      longstanding pain history. Obviously, the therapeutic benefit of all
      interventions is complete independent of the accompanying autonomic disorder and
      of a blockade of efferent fibers. A new heuristic model of the SMP mechanism is
      presented, including both experimental and clinical data. For reducing the risks
      of false positive or negative diagnosis of SMP and SIP, a diagnostic algorithm is
      proposed. This includes optimizing the technique, changes of interventional
      measures, and adequate monitoring both of analgesia and as well of the extend of
      efferent sympathetic blockade (e.g. measurement of sympathetic reflexes). The
      treatment recommendations in patients with SMP vary in dependence of the kind of
      disease. In SMP, invasive measures play an important, but only limited role
      within the comprehensive treatment concept. As an example a three-stage, symptom
      adapted treatment algorithm is demonstrated for CRPS, including also drug
      therapy, psychologic and physiotherapeutic approaches.

PMID- 12799970
TI  - [Potentialities and limitations of hypnosis for the treatment of pain].
AB  - With regard to the potentialities of hypnosis for the treatment of pain, relevant
      studies on hypnotic pain control are discussed. Studies with experimentally
      produced pain unanimously show that hypnosis is effective in controlling pain,
      whereas clinical studies are much more ambiguous in this respect. Three basic
      strategies of hypnotic pain control are outlined to which the different
      techniques can be subsumed: dissociative, associative, and symbolic strategies.
      Accountable for the limitations of hypnosis are some issues like hypnotic state,
      hypnotizability, rapport, hypnotic techniques, and pain as a multifactorial
      process. These issues are discussed and their contribution to contraindications
      are outlined. Especially the differences between symptom- and problem-oriented
      hypnotic approaches are highlighted.

PMID- 12799971
TI  - [Effect on morphine and other opioids on immune function].
AB  - PROBLEM: Already 1898 first clinical observations of a possible immune
      suppression after morphine intake were published. Today there are many reports
      describing opioid effects on nearly all parameters of the immune system. The
      question arises, whether there exists any evidence for clinical (harming) effects
      on patients. METHOD: Recent experimental and clinical publications are reviewed.
      Results are summarized, pathophysiological mechanisms and clinical conclusions
      discussed. RESULTS: Morphine and other opioids have immunomodulating effects on
      nearly all measurable parts of the immune system (macrophages, granulocytes, nk
      cells; mediators like Interleukin 1, 2 and 6, TNF). However, most studies did not
      include pain models, and in addition, high morphine doses were used. First
      studies using a combined pain/morphine-approach report immune stimulating
      effects. There are three pathophysiological mechanisms under discussion,
      including opioid receptors on immune competent cells, central opioid receptors
      activating the adrenergic system and opioid-induced steroid release with
      consecutive immunosuppression. It is completely unclear, if there is any
      relevance of these findings for clinical settings. CONCLUSIONS: The question
      whether use of opioids can harm chronic pain patients is unsolved. There is an
      urgent need for studies in clinical settings with clinical relevant parameters.

PMID- 12799972
TI  - [Hydromorphone--review of pharmacological properties and therapeutic efficacy
      with special regard to a controlled release preparation].
AB  - Hydromorphone is a micro receptor agonist opioid. According to WHO
      recommendations, hydromorphone is to be classified in step III of pain therapy.
      An oral formulation with a prolonged duration of action of 12 hours has been
      evaluated only recently. The controlled release capsule is especially suited for
      the regular twice a day administration in cases of severe and persistent pain.
      The oral formulation of hydromorphone increases the number of opioid analgesics
      available for pain therapy in step III. Hydromorphone is recommended when
      morphine fails to produce sufficient pain relief (despite increase of doses) or
      causes intolerable side effects (despite treatment of symptoms). In principle, no
      differences in efficacy of morphine and hydromorphone are to be expected.
      However, clinical experience shows that changing one opioid analgesic to another
      one can improve the treatment of patients so that hydromorphone may replace
      another opioid analgesic to which a patient fails to respond well or develops
      side effects. The dose of hydromorphone equivalent to 2 times 30 mg controlled
      release morphine is about 2 times 4 mg. The values for the absorption,
      bioavailability and maximum plasma concentration after the administration of
      controlled release hydromorphone every 12 hours -of three times the dose- are
      equivalent to those of an immediate release tablet given every 4 hours. In
      several open label and controlled studies, hydromorphone proved to be of good
      efficacy in the treatment of acute and persistent pain, especially in patients
      with severe cancer pain. With regard to the incidence of side effects, no
      significant differences between morphine and hydromorphone could be established.
      In general, the side effects of hydromorphone are typical for opioid analgesics.
      DISCUSSION: In conclusion, controlled release hydromorphone seems to be well
      suited for the control of severe chronic pain when given twice daily.

PMID- 12799973
TI  - [Computerized version of the pain experience scale: a study of equivalence].
AB  - PROBLEM: Comprehensive diagnosis of pain comprises assessment of subjectively
      felt pain as one necessary component. Modern approaches are multidimensional
      (differentiation between sensory and affective parts; multiple sub-aspects of
      sensory pain) and go far beyond single-item-methods, whose utility remain
      questionable not only regarding the contents but for measurement purposes as
      well. One of these modern instruments of pain assessment, the Pain Experience
      Scale (German: Schmerzempfindungsskala, SES), served as original for the
      development of a computerized version. The study aimed to establish whether this
      computer version is equivalent to the paper-pencil original. METHODS: Fifty-eight
      pain patients were recruited on admission to an in-patient pain management
      program. Half of them filled out the paper-pencil scale first, then worked on the
      computerized version. The others did so in reverse order. RESULTS: Analyses of
      means revealed nearly identical scores for both versions. Correlational analyses
      (computation of reliabilities for parallel tests) showed excellent
      correspondence. Analyses of order of presentation showed no effect. CONCLUSION:
      The two test versions are almost completely equivalent and can be used as a
      reliable tool in the practice of pain measurement. Moreover, validation data and
      questionnaire norms of the original version are completely applicable to the
      computerized version.

PMID- 12799974
TI  - [Quantitative thermotest - investigations of thermal and nociceptive afferents in
      neuropathy. Is a multicentric approach useful to investigate rare painful
      neuropathies?].
AB  - Disturbances of small afferent nerve fibres play an important role in painful
      neuropathies. Quantitative thermotest offers a possibility to quantify these
      disturbances that can not be detected by conventional electrophysiology. It is a
      psychophysical method to investigate thermal and nociceptive afferents by
      determining thermal thresholds. Former experiences have shown that quantitative
      thermotest can be a helpful tool not only in daily routine but also for research
      work concerning pathophysiological mechanisms of neuropathy. Therefore a
      multicentric approach to investigate rare painful neuropathies seems to be
      useful.

PMID- 12799975
TI  - [Radiological and electrodiagnostic methods in the diagnosis of chronic pain
      syndromes: chronic low-back pain].
AB  - BACKGROUND: This review of radiological and other procedures used in the
      diagnosis of (chronic) low-back pain is not intended to provide a complete
      evaluation of the methods employed, because the validity, specificity and
      sensitivity of the various diagnostic measures are the subject of so much
      controversy that a comprehensive discussion would be beyond the scope of the
      present overview. The choice of method depends not only on the clinical symptoms
      but also on the localisation of the pain, the aetiology of which may also be
      related to the age of the patient. CAUSES OF PAIN: Radiculary pain is usually
      derived from anatomical structures around the roots of a nerve, but it may be of
      discogenic origin. Diagnosis is achieved by a combination of radiological and
      neurophysiological methods. It is far more difficult to localise the cause of
      chronic pseudoradiculary low-back pain, because the main pathological structures
      can be the intra-articular portions of the vertebral body, the vertebral body
      itself, the ligamenta intervertebralia or the muscles. Using osteoporosis as an
      example, the structures of the spine which may cause pain are discussed and the
      possible diagnostic methods are described. In addition to diagnostic procedures
      like CT or MRT, use can also be made of interventional radiological methods like
      discography or facet-joint injections. Such techniques can be supplemented by
      diagnostic tests under local anaesthesia which may be useful in helping to define
      the pain. Repeated use of these procedures is only justified if the character of
      the pain changes or the pain suddenly becomes more pronounced. An algorithm is
      presented as a guideline only, because a more standardised approach does not give
      sufficient consideration to the personal experience of the individual user.

PMID- 12799976
TI  - [Differential diagnosis of joint pain].

PMID- 12799977
TI  - [Results of extracorporeal shock-wave application in lateral elbow tendopathy].
AB  - AIM: This review article focuses on a possible pain-alleviating effect of shock
      wave application in persistent lateral epicondylopathy of the elbow and compares
      the effects with data on other non-operative and operative procedures. METHODS:
      Patients who suffered from chronic tennis elbow for more than 12 months and were
      therefore referred for a surgical procedure were assigned at random to two groups
      of low-energy shock-wave therapy. Group I received a total of 3000 (3 x 1000)
      impulses of 0.08 mJ/mm(2), while group II (control group) received a total of 30
      (3 x 10) impulses of 0.08 mJ/mm(2). Follow-up examinations were carried out after
      3, 6, and 24 and 52 weeks. RESULTS: There was a significant improvement of pain
      and function in group I, with a good or excellent outcome in 52% of cases
      compared to 6% in group II at the last evaluation. CONCLUSION: Extracorporeal
      shock-wave application has a dose-dependent pain-relieving effect on chronic
      tendopathy of the lateral elbow.

PMID- 12799978
TI  - [Current conservative treatment of renal colic: value of prostaglandin synthesis
      inhibitors].
AB  - Prostaglandin synthesis inhibitors and parasympatholytic drugs are often used as
      analgetics in the case of renal colic. This paper analyzes how and whether these
      drug effects are important for the analgetic therapy. In an animal and in a human
      model with acutely obstructed kidneys we found that intravenous application of
      Indometacine and dipyrone significantly reduces renal pelvic pressure. The
      parasympatholytic drug hyoscine butylbromide did not produce any change of upper
      urinary tract dynamics. Inhibitors of prostaglandin synthesis thus effect
      pressure reduction in the renal pelvis, which is necessary for analgetic therapy.
      In contrast, hyoscine butylbromide does not have any influence on the acute upper
      urinary tract obstruction; consequently its usefulness in the treatment of renal
      colic is rather doubtful.

PMID- 12799979
TI  - [Predictability of pain after laparoscopic cholecystectomy with self-efficacy and
      locus of control].
AB  - The study consists of a prospective randomized controlled clinical trial of
      patients undergoing laparoscopic cholecystectomy. Besides medical and
      sociodemographic data, two personality factors--self-efficacy and locus of
      control--were found to predict postoperative pain. Self-efficacy describes the
      expectations of a person to successfully execute the behavior required to produce
      behavioral outcomes. Locus of control, in the extreme case, is a personality
      factor which is represented by an internal orientation in which the individual
      believes that rewards are brought about by his own action, versus an external
      orientation, in which the individual believes that rewards are the result of
      powerful others or chance factors and fate. We postulate that the two personality
      factors correlate with postoperative parameters of pain and that there are also
      multiple correlations between them. METHODS: For the two personality factors we
      applied two questionnaires which were given to the patients preoperatively. One
      is well established and the second one was developed and tested especially for
      this study by us. We used subjective pain, demand for and quantity of analgetics
      as parameters of postoperative pain until the 3rd day after surgery. RESULTS: The
      statistical analysis of 56 patients revealed that the two personality factors
      proved to be the most relevant and significant factors (p<0.05-0.001) to predict
      and also to explain high rate of variance up to 60% of postoperative pain.
      Patients with a high expectation of self-efficacy in pain management and an
      internal locus of control had a significantly lower subjective pain, demand for
      and quantity of analgetics than patients with low expectations of self-efficacy
      or a high external orientation with chance factor and fate in control. Medical
      and sociodemographic variables did not predict any parameters of pain. Some
      surgical factors were kept constant. DISCUSSION: These findings underline the
      importance of personality factors also in postoperative pain, which can be
      predicted by self-efficacy and locus of control. This result means for us that
      self-efficacy and locus of control influence the cognates of personal pain
      perception within the context of the individual history of experiences and seem
      to be changeable preoperatively by special psychological training.

PMID- 12799980
TI  - [A survey of physicians' knowledge about pain therapy with strong opioid
      analgesics].
AB  - INTRODUCTION: The WHO analgesic ladder, including the use of strong opioid
      analgesics for the treatment of cancer pain, is widely accepted. However, the use
      of opioids for the treatment of non-cancer pain is still controversial. This
      study investigates doctors' medical knowledge about basic aspects of pain
      management. Additionally, we determined whether the deficiencies in the treatment
      of patients suffering from pain are based on the rigorous national narcotic
      control system in Germany. METHODS: We investigated the juridical and technical
      knowledge of physicians specializing in pain therapy by a questionnaire. During a
      postgraduate course the knowledge about pain therapy according to the WHO
      analgesic ladder and the beliefs concerning the narcotic regulations in Germany
      were evaluated. The survey participants were asked to rate their attitudes on a
      10-point analogue scale (1=disagreement, 10=full agreement). The participants
      were also asked to indicate occupational criteria such as specialty, clinical
      practice area, and postgraduate years of practice. Descriptive statistics for the
      mean values were used. RESULTS: One hundred and forty-three questionnaires were
      completed. The majority of participants worked at departments of anaesthesiology.
      Some 51.1% of the participants had no specific multiple-copy prescriptions for
      opioid analgesics. Only 72% of the physicians knew from which governmental
      institution they could order multiple-copy prescriptions. In general, more
      doctors would prescribe opioids by the use of normal forms. The controlled
      substance laws were seen as an impediment by the majority of participants,
      without relevant differences as to their years of practice. The regulations were
      regarded as ineffective protection against illegal use of opioids. Treatment of
      pain with strong opioid analgesics was seen as beneficial for the patients. The
      use of strong opioids for long-term treatment was recommended, and psychological
      addiction was regarded as non-existent. CONCLUSION: Therapy with strong opioids
      is accepted practice, but significant deficits of legal and technical knowledge
      uphold the undertreatment of patients suffering from cancer and non-cancer pain.
      Patients with a legitimate need for pain relief by strong opioids are the
      unintended victims of tight narcotic regulations and deficits in medical
      education. An ease of regulatory conditions is mandatory to reduce the reluctance
      for prescribing opioids. On the other hand intensified continuous medical
      education is mandatory to reduce the undertreatment of patients with severe pain
      conditions.

PMID- 12799981
TI  - [The placebo trap].
AB  - Monodisciplinary orthopaedic pain therapy no longer measures up to international
      standards. In cases of chronic back pain, in particular, there is such a gulf
      between the clinical findings and the patient's subjective assessment that the
      symptoms cannot be attributed solely to so-called degenerative changes. Back pain
      patients are in great danger of becoming fixated on somatic symptoms due to an
      excess of diagnostic procedures or incorrect diagnoses, of being treated purely
      somatically on the basis of associated findings, and of suffering irreversible
      damage from invasive management of such findings. Despite the wealth of empirical
      evidence, it remains difficult to expand the everyday concept of illness and its
      causes to include not only physical and biological factors but also social and
      emotional disturbances. Particularly physicians with a purely biological concept
      of pain have not learned to take note of affective relational factors and
      incorporate them into their diagnostic assessment. The decision to undertake
      invasive diagnostic or therapeutic procedures then frequently represents the
      doctor's reaction to feelings of irritation or helplessness. If this situation is
      to change, an interdisciplinary concept of pain must be made a part of medical
      training, and scientific findings must be presented in such a way that they can
      be integrated into routine daily practice.

PMID- 12799982
TI  - [Analgesic and analgesia-potentiating action of B vitamins].
AB  - Disregarding pain resulting from vitamin deficiency, an analgesic effect seems to
      be exerted only by vitamin B1 (thiamine), vitamin B6 (pyridoxines), and vitamin
      B12 (cobalamine), particularly when the three are given in combination. The
      analgesic effect is attributed to an increased availability and/or effectiveness
      of noradrenaline and 5-hydroxytryptamine acting as inhibitory transmitters in the
      nociceptive system. In animal experiments, high doses of these vitamins
      administered alone or in combination inhibited nociceptive behavior and depressed
      the nociceptive activity evoked in single neurons of the dorsal horn of the
      spinal cord and in the thalamus. Moreover, they were found to enhance the
      antinociceptive effect of non-opioid analgesic agents on withdrawal reflexes.
      Clinical data fail in most cases to meet current standards of evaluation
      (randomization, double-blindness). Still, it appears that high doses of the
      vitamins B1, B6, and B12 administered separately or in combination can alleviate
      acute pain and potentiate the analgesia caused by non-opioid analgesics such as
      the NSAIDs and metamizol (dipyrone). Therapeutic effects are observed in
      neuropathic pain and pain of musculoskeletal origin. Vitamin B6 is effective in
      the carpal tunnel syndrome which, however, is attributed at least in some cases
      to vitamin B6 deficiency. It is also worth noting that the B vitamins are shown
      to enhance the beneficial effect of diclofenac in acute low-back pain so that
      either the duration of treatment or the daily dose of diclofenac may be reduced.
      The use of high doses of vitamin B6 may be limited by a neurotoxic effect. The
      effectiveness of B vitamins in depressing chronic pain has not been established.
      It would be interesting to know if the B vitamins are of use as adjuvants in the
      treatment of tumor pain.

PMID- 12799983
TI  - [Weak opioids. Meta-analysis for the therapy of chronic pain].
AB  - Weak opioids have a maximal dose (ceiling effect), and their distribution and
      prescription is not controlled by German narcotic laws. In a literature search
      (Medline 1963-1995) and our own literature database on pain treatment, 58
      publications were identified. These reported about 130 comparisons of weak
      opioids with different analgesics. The statistical parameters of a meta-analysis
      were not calculated, due to great differences of the study design and the
      examined drugs. The results of this literature analysis demonstrate the analgesic
      efficacy of weak opioids in chronic pain. Non-opioid analgesics and strong
      opioids, however, have greater potency. These results are based mainly on single
      dose studies; controlled long-term studies are required. Especially the risk of
      serious complications involving the gastrointestinal tract, kidney and blood
      cells during long-term treatment with non-opioid analgesics or weak opioids needs
      to be evaluated. In addition, the combination of non-opioid analgesics and weak
      opioids versus the combination of nonopioid analgesics and placebo or low-dose
      strong opioids has to be investigated. The results of this literature analysis
      support the use of weak opioids in the symptomatic treatment of chronic pain,
      though the evidence of the available literature is limited. It can be recommended
      to prescribe weak opioids according to the WHO ladder in combination with non
      opioid analgesics. If this combination provides no adequate analgesic efficacy,
      however, the use of strong opioids must not be delayed.

PMID- 12799984
TI  - [Treatment of tension-type headache. Recommendation of the German Migraine and
      Headache Society].

PMID- 12799985
TI  - [Active euthanasia or better palliative therapy?].
AB  - The Dutch Supreme Court ruled that in exceptional instances, physician-assisted
      suicide might be justifiable for patients with unbearable mental suffering but no
      physical illness. A recent report shows that explicit requests for physician
      assisted suicide are not uncommon in psychiatric practice in the Netherlands.
      Some of those requests were granted and their medical background was described.
      Psychiatric consultation for medical patients who request physician-assisted
      suicide is relatively rare. Therefore is seems to be necessary to establish
      better palliative care for the terminally ill. When psychiatrists help their
      patients to commit suicide there is a danger of abuse and "slippery slope".

PMID- 12799986
TI  - [Differential diagnosis of polyarthritis pain syndrome of the locomotor
      apparatus].
AB  - Widespread pain syndromes of the musculoskeletal system present to general
      practitioners, internists, neurologists and orthopedic surgeons every day. The
      syndromes may result both from organic diseases (inflammatory joint diseases,
      rheumatic manifestations of organ diseases) as well as dysfunctional syndromes,
      the latter including mainly biomechanically induced syndromes and fibromyalgia.
      The approach is predominantly clinically oriented and requires laboratory means
      or technical procedures only in a limited extend. The duration of history, the
      recognition of synovitis and of myofascial trigger points or of integumental
      tender points allow in most patients to achieve appropriate diagnostic criteria.

PMID- 12799987
TI  - [Ethical aspects in the treatment of pain].
AB  - Commonly pain has been seen as a warning sign reacting to a source of pain. This
      process displays the wisdom of the body and its ability to function well. But
      this concept cannot necessarily be upheld when, due to illness, integrity of the
      body can be neither the presupposition nor the goal of treatment. The ethical
      question is not to decide which perspective (pain as a vital sign or pain as
      catastrophe) is the dominant one. Medical ethics must acknowledge pain as a
      process of human destruction, and it must interpret the treatment of pain as an
      endeavour which makes life possible again, or strengthens its remaining elements.
      When pain goes beyond the resources of the human being to form his/her life, the
      border between meaningful and meaningless pain is crossed. A case from an
      obstetrical ward is used to demonstrate three central principles of the treatment
      of pain: (1) Understanding the pain as the end of all interests, as making life a
      burden or as evacuating the ego. 2. Respect of the autonomy of the patient by
      informing him/her about the experiences which he/she gets rid of during
      analgesia, or by establishing the possibilities that PCA or time-contingent
      medication offer. 3. The multidimensional therapy of pain: i.e. all groups of
      caregivers must be involved, because it is not important to know which
      perspective is the best, but that no single perspective can stand alone. These
      principles must be taken into account even when the possibilities of effective
      pain relief are exhausted. Sometimes the debate on the practice of euthanasia
      seems to replace the medical goal of honest treatment of the patient's pain.

PMID- 12799988
TI  - [The opioid tramadol demonstrates excitatory properties of non-opioid character-
      a preclinical study using alfentanil as a comparison].
AB  - Tramadol, an analgesic with mean potency one tenth that of morphine is used
      regularly for the treatment of chronic and postoperative pain. Previous reports
      have indicated that tramadol may induce seizure activity when given together with
      a selective serotonin reuptake inhibitor (SSRI). Therefore, its major mode of
      action may be questioned which purportedly is due to binding with the opioid
      receptor and partly due to the inhibition of monoamine reuptake. We therefore set
      out to study its potential in inducing seizure activity and to quantify its
      effect on EEG-power spectra and on the central modulation of sensory afferents in
      awake and trained dogs (n=7). In order to demonstrate if opioid receptors
      mediated these effects, incremental doses of tramadol were given which was
      followed by naloxone for possible reversal. After a wash-out period the same
      animals were exposed to graded doses of alfentanil, a pure mu-receptor agonist.
      Again this was followed by the opioid antagonist naloxone for reversal.The
      electroencephalogram (EEG) and the event-related evoked potentials (SEP) were
      used to demonstrate possible excitatory effects. In order to derive the SEP the
      front paw was stimulated electrically (Digi Stim II trade mark ) while the evoked
      potentials were picked up contralaterally from the somatosensory cortex using
      stick-on electrodes. 256 sweeps were averaged (Lifescan) and the peak-to-peak
      amplitude was measured to demonstrate CNS excitation compared to control (%).
      Additionally, the raw electroencephalogram was viewed for epileptogenic changes
      and its power computed into the various power bands alpha, beta, delta und theta
      using FFT over a time epoch of 60 s. Following control, graded doses of either
      tramadol (2-5-10 mg/kg i.v.) or alfentanil (10-30-60 microg/kg i.v.) were given
      every 15 min while the EEG and the SEP were recorded. Thereafter naloxone (20
      microg/kg i.v.) was injected for reversal. Tramadol did not suppress the
      amplitude of the SEP at any dose. High doses (>5 mg/kg i.v.) resulted in an
      increase (+100%) of the amplitude of the evoked potential. This was accompanied
      by short-term muscle fibrillations, and a short-term spike-and-wave activity in
      the EEG followed by a long-lasting theta-dominance. These effects could not be
      reversed by naloxone. In contrast to tramadol, alfentanil induced a dose-related
      depression of amplitude in the SEP with a maximum of 82% suggesting a depressive
      effect of modulation of afferents in the sensory cortex. This effect was fully
      naloxone reversible and was followed by a rebound in amplitude of the SEP
      together with an increase in fast beta-waves in the EEG. Tramadol very little
      mediates its central action via the mu-opioid receptor as the present effects
      were not naloxone reversible. Consistent with the results is the very low
      affinity of tramadol to the opioid receptor which is several thousand times less
      than that of morphine. Most likely, inhibition of central norepinephrine and
      serotonin reuptake as well as the reduction in 5-HT-turnover may contribute to
      the effects of tramadol. Due to the monoamine reuptake inhibition an increase in
      transmission may result, triggering off excitatory phenomena with spike-and-wave
      activity in the CNS. Such excitatory effects, however, may only be seen when
      tramadol is used in doses exceeding the therapeutic range.

PMID- 12799989
TI  - [Autonomic dysfunction in migraine und tension-type headache--pilot study].
AB  - Autonomic nervous system (ANS) dysfunction in migraine has been hypothesized
      during the last years. However, the pathophysiological relevance of this
      dysfunction on the etiology and the maintenance of the headaches remains unclear.
      The aim of this study was to investigate connections between the ANS dysfunction
      and the clinical appearances of the pain and its processing in migraine and
      tension-type headache (TTH). METHODS: Ten migraine-patients (31,4+/-10,6 years)
      and ten TTH-patients (49,3+/-14,6 years) underwent a cardiovascular reflex
      testing during headache-free intervals. A questionnaire was obtained to determine
      the patients' clinical pain-symptoms. RESULTS: The ANS function testings showed
      sympathetic hypofunction in both groups of patients. In the migraine-group, there
      was a significant correlation between the pain-intensity and the extent of the
      autonomic dysfunction (r=0,82) In the TTH-group, we found a correlation between
      the results of the orthostatic test and the v. Zerssen-depression-scale (r=0.69).
      CONCLUSIONS: These results suggest a sympathetic dysfunction in both headache
      syndromes and suggest that the ANS plays an important role on the pathophysiology
      and the maintenance of the headaches.

PMID- 12799990
TI  - [What is certain in pain therapy? The analgesic potency of neuroleptics in the
      treatment of chronic pain. A metaanalysis].
AB  - The wide variety of therapeutic effects make neuroleptics potent drugs in the
      treatment of pain. Until now there has been no proof of their analgesic potency;
      in spite of this fact, neuroleptics are used to treat chronic pain states on the
      assumption that they do have analgesic potency. A metaanalysis was performed and
      48 publications reviewed. Thirty-four, the majority of the studies, are case
      reports, retrospective analyses or non-randomised cohort studies. Most of these
      reports attest to a positive effect. However, only ten out of fifteen studies
      with a higher statistical study power describe a possible analgesic effect. None
      of the studies could differentiate between the effects of analgesia and sedation
      of the drugs used. The metaanalysis provides no evidence of intrinsic analgesic
      properties of neuroleptics for their use as adjuvant analgesics.

PMID- 12799991
TI  - [Not Available].

PMID- 12799992
TI  - Medial olivocochlear efferent reflex in humans: otoacoustic emission (OAE)
      measurement issues and the advantages of stimulus frequency OAEs.
AB  - Otoacoustic emissions (OAEs) are useful for studying medial olivocochlear (MOC)
      efferents, but several unresolved methodological issues cloud the interpretation
      of the data they produce. Most efferent assays use a "probe stimulus" to produce
      an OAE and an "elicitor stimulus" to evoke efferent activity and thereby change
      the OAE. However, little attention has been given to whether the probe stimulus
      itself elicits efferent activity. In addition, most studies use only
      contralateral ( re the probe) elicitors and do not include measurements to rule
      out middle-ear muscle (MEM) contractions. Here we describe methods to deal with
      these problems and present a new efferent assay based on stimulus frequency OAEs
      (SFOAEs) that incorporates these methods. By using a postelicitor window, we make
      measurements in individual subjects of efferent effects from contralateral,
      ipsilateral, and bilateral elicitors. Using our SFOAE assay, we demonstrate that
      commonly used probe sounds (clicks, tone pips, and tone pairs) elicit efferent
      activity, by themselves. Thus, results of efferent assays using these probe
      stimuli can be confounded by unwanted efferent activation. In contrast, the
      single 40 dB SPL tone used as the probe sound for SFOAE-based measurements evoked
      little or no efferent activity. Since they evoke efferent activation, clicks,
      tone pips, and tone pairs can be used in an adaptation efferent assay, but such
      paradigms are limited in measurement scope compared to paradigms that separate
      probe and elicitor stimuli. Finally, we describe tests to distinguish middle-ear
      muscle (MEM) effects from MOC effects for a number of OAE assays and show results
      from SFOAE-based tests. The SFOAE assay used in this study provides a sensitive,
      flexible, frequency-specific assay of medial efferent activation that uses a low
      level probe sound that elicits little or no efferent activity, and thus provides
      results that can be interpreted without the confound of unintended efferent
      activation.

PMID- 12799998
TI  - Classification and management of early complications in open lumbar
      microdiscectomy.
AB  - Complications and side effects in any kind of surgery, especially in spine
      surgery, should be evaluated to prevent those problems in the future. Since
      retrospective studies are of minor value and randomized controlled studies for
      complications are impossible to perform because of ethical and legal reasons, so
      called "expert opinion" has to take their place in evidence-based medicine. On
      the basis of an analysis of the results of three spine centers together with the
      opinions of experienced spine surgeons, the authors have drawn up a
      classification of complications in open lumbar disc surgery and recommendations
      on how to manage common complications such as excessive bleeding, dural opening,
      nerve root lesions and recurrent disc herniation. The management of
      intraoperative complications should have the same training in microdiscectomy
      instructional courses as the operation itself.

PMID- 12799999
TI  - Whiplash injury: cases with a long period of sick leave need biomechanical
      assessment.
AB  - A total of 668 cases of cervical spine disorders (CSD) sustained in automotive
      collisions were analysed. All cases had a minimum sick leave duration of 4 weeks.
      To evaluate these cases a scheme was developed that takes into account technical,
      medical, and biomechanical aspects. For each case, the delta-v value of the
      underlying collision was estimated, the medical files were analysed, and a QTF
      (Quebec Task Force) grade was assigned. In addition, the medical history of the
      patient was reviewed. It was found that the QTF grade for patients with pre
      existing damage of the neck or pre-existing signs differed significantly from
      those patients without such a history. The overall assessment, which stated the
      extent to which the symptoms claimed could be explained by the impact, was also
      found to be significantly influenced by a history of neck injury. The results of
      the study showed that in about 50% of the cases where the technical analysis
      alone would not suggest that the symptoms shown could be explained by the impact,
      those symptoms could be explained when patient history and the collision
      circumstances were taken into consideration. It also found that medical
      evaluation based on a QTF grade alone cannot assess the explicability of claimed
      CSD without taking into account the collision circumstances. Therefore, the
      assessment of critical individual relevant biomechanical factors is necessary.

PMID- 12800000
TI  - Burst fractures of the thoracolumbar spine: changes of the spinal canal during
      operative treatment and follow-up.
AB  - Although multiple studies have concluded operative decompression of a
      traumatically narrowed spinal canal is not indicated because of spontaneous
      remodeling, instrumental decompression is frequently used as part of the
      operative treatment of spinal fractures. To investigate the process of
      remodeling, we studied the diameter of the spinal canal in 95 patients with burst
      fractures at the thoracolumbar junction (T9-L2). To measure and compare the
      spinal canal's diameter we used either computed tomography (CT) scans or
      radiographs, made preoperatively, postoperatively, after 9 months and after 24
      months. In lateral plain radiographs we found that the initial percentage of
      cases with bony canal narrowing preoperatively of 76.5 was reduced to 18.4%
      postoperatively, to 8.2% at 9 months, and to 2.4% at 24 months. In CT scans in a
      selection of patients, the mean residual diameter of the spinal canal was 53%
      preoperatively and 78% at 24 months. The posterior segmental height increases
      during operation and decreases in the respective periods after operation. So
      ligamentotaxis can only play a role in the perioperative period. We conclude that
      a significant spontaneous remodeling of the spinal canal follows the initial
      surgical reduction. Two years after operation, bony narrowing of the spinal canal
      is only recognizable in 2.4% of the patients on plain lateral radiographs. The
      remodeling of the spinal canal can be seen on plain radiographs, although not as
      accurately as on CT scans.

PMID- 12800001
TI  - Functional outcome in patients with thoracolumbar burst fractures treated with
      dorsal instrumentation and transpedicular cancellous bone grafting.
AB  - The aim of the study was to develop an insight into the impairments in spinal
      fracture patients, operatively treated with an internal fixator, and also into
      their ability to participate in daily living, return to work and quality of life
      as defined by the World Health Organization. Nineteen patients operated for a
      type A fracture of the thoracolumbar spine (T9-L4) between 1993 and 1998 in the
      University Hospital Groningen, the Netherlands, aged between 18 and 60 years,
      without neurological deficit were included in the study. Operative treatment
      consisted of fracture reduction and internal fixation using the Universal Spine
      System, combined with transpedicular cancellous bone grafting and dorsal
      spondylodesis. No ventral fusion operations, laminectomies or discectomies were
      done. Restrictions in body function and structure were measured on radiographs
      and in functional capacity tests, such as lifting tests and ergometry.
      Restrictions in activities were studied with the Visual Analogue Scale (VAS)
      Spine Score and the Roland Morris Disability Questionnaire (RMDQ). Restrictions
      in participation/quality of life were analysed with the Short Form 36 (SF36) and
      described in the return to work status. The radiological results are comparable
      to the literature. The reduction of the anterior wedge angle was followed by a
      gradual partial loss of intervertebral angle and regional angle. The maximum
      oxygen uptake (VO2-max) was reduced in only 8.3% of the patients. Arm and trunk
      lift was within the normal range in 87% and 80% of the patients respectively, but
      only 53% of the patients were able to perform a leg lift within the normal range.
      A mean RMDQ score of 4.0 positive items (SD 6.0) was found, and the mean VAS
      Spinal Score was 79.4 (SD 25.0), both better than in other series. No significant
      differences compared to the values of a comparable (healthy) age group could be
      identified in any variable of the SF36. A high correlation was seen between RMDQ,
      VAS Spine Score and the SF36 categories. No correlation was found between the
      anterior wedge angle and the regional angle on the one hand, and functional
      capacity tests or questionnaire scores on the other. Of the patients in paid
      employment before the trauma, 87% had returned to work at follow-up. About 50% of
      the patients had been obliged to change the intensity of their work or the kind
      of work they performed after the injury and treatment. In this matter, leg
      (muscle) performance seems a more important factor than overall condition (VO2
      max). The results of the study indicate that patients with thoracolumbar spinal
      fractures without neurological deficit, treated with dorsal instrumentation,
      perform like healthy people 3-8 years after injury, according to the RMDQ, VAS
      Spine Score and SF36 results. Physical capacity tests reveal that leg (muscle)
      performance seems a more important factor in impairment than arm lift or overall
      condition.

PMID- 12800002
TI  - Rib deformity in scoliosis.
AB  - Rib deformity in scoliosis is of interest because it may help in the diagnosis,
      and also, in some pronounced cases, it may need correction by costoplasty. There
      are, however, debates about its use in diagnosis, because some authors think that
      rib deformity is not closely related to either the magnitude or the extent of
      rotation of the curve. In order to define the relation between rib deformity and
      scoliosis, 11 patients were recruited who were to undergo scoliosis surgery and
      thoracoplasty, and anteroposterior (AP) T1-S1 standing radiographs, computerized
      tomography (CT) scans, and three-dimensional (3D) reconstructions were obtained.
      From the radiographs, the most rotated vertebra, the Cobb angle, the apex and the
      type of the curve were determined. From the CT scans and 3D reconstructions, the
      exact level of the rib deformity measured was matched with the corresponding
      vertebral level. In this way, the most rotated vertebra and the most prominent
      part of the rib cage deformity were identified. The most rotated vertebra was
      found to be at the same level in both radiographs and CT scans in only five
      patients. In the rest of the patients, CT scans showed it either one level higher
      or lower than it appeared on the radiograph. The most prominent part of the rib
      cage deformity was at the same level as the most rotated vertebra in two
      patients, and in the rest of the patients it was one, two or three vertebral
      levels lower. There was no association between the Cobb angle, vertebral rotation
      and rib deformity. A CT scan is necessary preoperatively in patients who will
      undergo a costoplasty, to determine the exact levels of the prominence. However,
      a scanogram or a 3D reconstruction is required for exactly matching the most
      prominent part of the rib cage deformity to the corresponding vertebral level.

PMID- 12800003
TI  - Results of hemivertebrectomy and fusion for symptomatic thoracic disc herniation.
AB  - We retrospectively analysed ten consecutive patients (age range 32-77 years)
      treated surgically from 1994 to 1999 for symptomatic thoracic disc herniation
      between the 6th and 12th thoracic discs. Clinically, eight patients had varying
      grades of back pain and eight patients had paraparesis. Radiography showed
      calcification in 50% of the herniated discs. Two patients had two-level thoracic
      disc herniation. Hemivertebrectomy followed by discectomy and fusion was carried
      out in all patients. Instrumentation with cages was performed in eight patients
      and bone grafting alone in two patients. The average follow-up was 24 months
      (range 13-36 months). Six patients had an excellent or good outcome, three had a
      fair outcome and one had a poor outcome. One patient had atelectasis, which
      recovered within 2 days of surgery. Another patient had developed complete
      paraplegia, detected at surgery by SSEPs, and underwent resurgery following
      magnetic resonance (MR) scan with complete corpectomy and instrumented fusion. At
      2 years, she had a functional recovery. The patient with poor outcome had
      undergone a previous discectomy at T9/10. He developed severe back pain and
      generalised hyper-reflexia following corpectomy and fusion for disc herniation at
      T10/11. We advocate anterior transthoracic discectomy following partial
      corpectomy for symptomatic thoracic disc herniation between the 6th and 12th
      thoracic discs. This procedure offers improved access to the thoracic disc for an
      instrumented fusion, which is likely to decrease the risk of iatrogenic injury to
      the spinal cord.

PMID- 12800004
TI  - Fluid flow in an animal model of post-traumatic syringomyelia.
AB  - More than a quarter of patients with spinal cord injury develop syringomyelia,
      often with progressive neurological deficit. Treatment options remain limited and
      long-term failure rates are high. The current poor understanding is impeding
      development of improved therapies. The source and route of fluid flow into
      syringes has been investigated using cerebrospinal fluid (CSF) tracers. Previous
      work using a model of canalicular syringomyelia has shown that fluid enters the
      dilated central canal from perivascular spaces. The aim of this study was to
      determine the source and route of fluid flow in an animal model of
      extracanalicular (post-traumatic) syringomyelia. A model of post-traumatic
      syringomyelia was established in 25 Sprague-Dawley rats with intraparenchymal
      injections of quisqualic acid and kaolin-induced arachnoiditis. Rats survived for
      6 weeks before injection of the CSF tracer horseradish peroxidase into the
      cisterna magna. Examination of the spatial distribution of horseradish peroxidase
      at 0, 3, 5, 10, or 20 min after injection was used to determine the route of
      fluid flow. Horseradish peroxidase rapidly spread to the ventromedian fissure,
      perivascular spaces, central canal, and extracanalicular syrinx. Flow occurred
      into the syrinx prior to significant perivascular flow in the rostral spinal
      cord. Preferential flow into the syrinx occurred from the perivascular spaces of
      the central penetrating branches of the anterior spinal artery in the grey
      matter. Transparenchymal flow into the syrinx was less prominent than
      perivascular flow. This is the first report of fluid flow within the spinal cord
      in a model of post-traumatic syringomyelia. Fluid from perivascular spaces moves
      preferentially into extracanalicular syringes and the surrounding parenchyma.
      Obstruction to CSF flow and loss of compliance from traumatic arachnoiditis might
      potentiate fluid flow in the perivascular space.

PMID- 12800005
TI  - A non-invasive technique for measurement of cervical vertebral angle: report of a
      preliminary study.
AB  - Non-invasive methods have traditionally been used to assess spine positioning and
      range of motion. Recently, the use of prediction models derived from external
      stick markers and videographic analysis has been shown to be effective at
      predicting lumbosacral and segmental lumbar vertebral angles. The objective of
      this study was to develop a similar non-invasive method to predict cervical
      vertebral inclination in forward head flexion. Fourteen subjects with no history
      of trauma or inflammatory or arthritic disorders (mean age: 25+/-1 years)
      participated in this study on a voluntary basis. Radiographic and videographic
      measurements of four external markers (C0, C2, C6, C7) were taken for each
      subject at three different static head positions (neutral, and 30 degrees and 60
      degrees of flexion). The data obtained from nine subjects with normal cervical
      configuration (lordosis) were used to develop statistical models predicting the
      radiographic segmental angles (dependent variables) from external markers
      (independent variables). A multiple regression model was developed for each
      vertebra (C1 to C6). These regression models predict the inclination of each
      cervical vertebra at three different neck angles with positional data derived
      from the four external skin markers. Adjusted R2 values of 0.97, 0.93, 0.93,
      0.96, 0.95 and 0.89 were obtained for C1, C2, C3, C4, C5 and C6, respectively.
      The prediction models developed in this study can explain a large part of the
      variance for the relative contribution of each vertebral segment to global neck
      flexion and provide a greater accuracy then using external stick markers only.
      These models were not able to adequately predict the vertebral angular
      positioning of subjects presenting a cervical alordosis or kyphosis.

PMID- 12800006
TI  - A new technique for the treatment of lumbar far lateral disc herniation:
      technical note and preliminary results.
AB  - A newly designed technique for a minimally invasive approach to the laterally
      herniated disc is presented. Fifteen patients suffering from far lateral disc
      herniation (extraforaminal) were operated according to this technique. Through a
      small skin incision (1.5 cm), the paraspinal muscles are spread by dilators,
      until a working channel of 9 mm inner diameter and 11 mm outer diameter can be
      placed. The next steps are done through this channel using the surgical
      microscope. No bone resections are necessary and the facet joints are left
      untouched. However, partial resection of the intertransverse ligament may be
      necessary. The mean follow-up period for these 15 patients was 11.5 months, and
      they were evaluated by using the visual analogue scale (VAS) and the Oswestry
      Disability Index (ODI). The average surgical time was 43 min. The ODI improved
      from 30.6 (preoperative) to 14.3 (postoperative). The VAS of leg pain improved
      from 7 (preoperative) to 3.6 (postoperative), which represented a statistically
      significant improvement at the significance level of (P<0.01). No intra-operative
      or early postoperative complications occurred. However, one recurrence did occur,
      which was treated by the same technique. This technique combines the advantages
      of three-dimensional visual control (operating microscope) with the minimal
      surgical trauma of endoscopic techniques, while avoiding some of the shortcomings
      of both the microsurgical and endoscopic techniques.

PMID- 12800007
TI  - Intraspinous postlaminectomy pseudomeningocele.
AB  - Pseudomeningoceles are uncommon complications of lumbar surgery. They are
      encapsulated cerebrospinal fluid collections developing extradurally as a
      consequence of incidental dural tears. They are typically located in the
      paraspinal compartment and occasionally reach the subcutaneous space. We describe
      the case of a patient in whom a postlaminectomy pseudomeningocele developed over
      a 10-year period within the L5 spinous process and remained completely encircled
      within its bony boundaries. The surgical implications of this finding are
      discussed.

PMID- 12800008
TI  - Schwann cell invasion of the conus medullaris: case report.
AB  - As Schwann cells possess regenerative capabilities there is intense interest
      concerning their role in central nervous system (CNS) regeneration. We report on
      a case of an intramedullary schwannoma involving the conus medullaris and spinal
      cord above it. We discuss the possible origin of these cells and the mechanisms
      by which these cells may invade the CNS. We offer imaging and discuss
      experimental studies to support our hypothesis. This case concerns a 48-year-old
      man, who presented with a 6-month history of bilateral lower extremity weakness.
      Magnetic resonance imaging (MRI) revealed an intramedullary tumour extending from
      the conus to T11. At operation, following laminectomy and durotomy, a schwannoma
      was dissected free from the conus. Total gross resection of tumour was achieved.
      The patient made an uneventful and full recovery. This case shows that Schwann
      cells can invade the CNS. Manipulation of the transitional zone astrocytic
      barrier may offer a potential avenue for Schwann cells to enter the CNS in
      pathological states.

PMID- 12800009
TI  - Remodelling of the sacrum in high-grade spondylolisthesis: a report of two cases.
AB  - Two young patients are described, who were operated on for high-grade
      spondylolisthesis. A good posterolateral fusion was achieved, without
      decompression and without reduction. The clinical course was favourable, the
      tight hamstring syndrome resolved. Disappearance of the posterior-superior part
      of the sacrum and of the posterior part of the L5-S1 disc was observed on
      comparing pre- and postoperative magnetic resonance (MR) images. This resulted in
      normalisation of the width of the spinal canal. Around the L5 nerve roots in the
      L5-S1 foramina some fat reappeared. These anatomical changes on MRI could play a
      role in the disappearance of clinical symptoms.

PMID- 12800010
TI  - [Stumbling-blocks: initiating a psychosomatic pain clinic].
AB  - OBJECTIVE: Despite psychosocial factors playing an important role in the course
      of chronic pain disorder, there is a noticeable imbalance between demand and
      availability of psychosomatic care for these patients. This led us to establish a
      psychosomatic pain clinic within the framework of our outpatient clinic at the
      Department of Psychosomatic Medicine and Psychotherapy at the Central Institute
      of Mental Health, Mannheim, Germany. A recent study aimed at the evaluation of
      sociodemographic variables, state of chronification, symptom load and psychiatric
      comorbidity. Additionally we wanted to determine whether existing conditions at
      our hospital can be considered suitable for those patients. METHODS: During the
      clinic's first year we assessed 40 consecutive patients based on a psychosomatic
      interview as well as a set of psychometric questionnaires (BDI, STAI, SCL-90-R).
      To detect differences between pain patients and psychotherapy inpatients, we
      compared the two groups in terms of sociodemographic variables and symptom load.
      RESULTS: Most pain patients were in advanced states of chronification, showing
      extensive psychiatric comorbidity, particularly anxiety and depressive syndromes.
      Drug addiction was found more infrequently. Use of the before mentioned
      questionnaires prevented us from underestimating existing anxiety syndromes. Pain
      patients differed substantially from psychotherapy inpatients in terms of age,
      education, family status and symptom load. CONCLUSIONS: Our examination routine
      effectively demonstrated the special needs of chronic pain patients. As there is
      significant demand for psychosomatic intervention in those patients, earlier
      referral appears highly desirable. As pain patients differ also greatly from the
      remaining hospital population, specialized therapeutic concepts must be
      developed.

PMID- 12800011
TI  - [Outcome-quality of treatment for headache on primary care conditions].
AB  - BACKGROUND: Little is known about the outcome-quality of treatment for headache
      on primary care conditions in Germany. METHODS: All physicians (2100) of middle
      franconia, a bavarian greater district with 1,6 Mio. inhabitants, involved in
      outpatient management were asked to include consecutively patients in the study
      which suffer from migraine (at least 2 attacks/month) and/or tension type
      headache (at least 8 days/month) of at least 4 weeks duration. Before and after a
      6 months interval patients documented the following outcome data in a
      questionnaire: pain intensity during the last attack (numeric rating scale), pain
      dependent disability (Brief Pain Inventory, German version), health related
      quality of life (SF-36, German version) and depressivity (Allgemeine
      Depressionsskala). The pain chronification state (Mainz Pain Staging System) has
      been assessed by the physician. Therapy was not standardized and included the
      natural spectrum of medicamental and non-medicamental therapy of headache.
      Agreement of therapy with recommendations of the "Arzneimittelkommission der
      Deutschen Aerzteschaft" has been assessed. RESULTS: 24 physicians participated in
      the study. Pre-post-data of 80 patients (46+/-14 y) could be analysed. Initially
      67% were classified in pain chronification state I, 27% in state II and 6% in
      state III. Medicamental therapy agreed with recommendations in approximately 50%
      of patients, non-medicamental therapy has been used rarely. The pain intensity,
      pain dependent disability, depression and quality of life improved significantly.
      45% and 55% of patients improved in at least 2 of 6 outcome-parameters by 30% of
      baseline value or by half standard deviation of the corresponding pre-post
      differences, respectively. The latter outcome-measure reflects a medium effect
      size. CONCLUSIONS: On primary care conditions about 50% of patients suffering
      from migraine and/or tension type headache (predominantly low chronification
      stae) perceive a therapy effect that corresponds to a medium effect size.

PMID- 12800012
TI  - [Measuring disability of patients with low-back pain--validation of a German
      version of the Roland & Morris disability questionnaire].
AB  - INTRODUCTION: In this study three instruments measuring disability of patients
      with low-back pain are presented and evaluated: (1) the Behinderungsfragebogen
      (RM) - a German version of the Roland & Morris disability questionnaire (RDQ) (2)
      a numerical rating scale measuring disability in general and (2) eight numerical
      rating scales measuring specific dimensions of disability (standing, sitting,
      walking, driving a car, carrying light loads, carrying heavy loads, sleeping, and
      sexual intercourse). METHODS: The psychometric evaluation, including the item
      analysis, test reliability, test validity, and responsiveness of the instruments,
      is based on two samples. Sample A comprises 345 patients with low-back pain: 282
      of these patients took part in the Swiss multicentre intervention study testing
      the effectiveness of in-patient rehabilitation of sub-chronic and chronic low
      back pain under an integrative group treatment program. The instruments were
      administered at different times in the therapeutic process (t1: at hospital
      admission; t4: follow-up after one year). 63 patients were hospitalized
      (orthopedic or rheumatological units) for medical examinations (myelography or
      infiltration of facets) or rehabilitation of low-back pain. The instruments were
      administered twice within 24 h to measure test-retest correlation. In order to
      determine the psychometric parameters as accurately as possible, the two samples
      were examined jointly. Sample B is composed of 41 patients with low-back pain
      participating in the study "Pradiktoren des Erfolgs bei stabilisierenden
      Wirbelsauleneingriffen" (Success predictors of effectiveness of surgical
      interventions for spinal stabilization). RESULTS: All instruments proved to be
      generally reliable and valid (high or medium correlations with each other and
      with a German version of the Oswestry Disability Questionnaire) as well as
      responsive tools for measuring the momentary disability of patients with back
      pain. The psychometric examination of the test validity showed that patients'
      perceptions of their disability were influenced by their psychological well
      being. The correlation between the 3 instruments and physical tests was low. The
      RM is not a homogeneous instrument. Factor analysis (principal component
      analysis, rotation Varimax) indicated 6 factors. Because of the small number of
      items for each factor it is not appropriate to treat RM in terms of dimensions of
      disability. CONCLUSIONS: The RM is an instrument measuring patients' perception
      of their disability that offers simple, fast practicability for patients and
      tester. The 2 rating scales: The 8 numerical rating scales measuring specific
      dimensions of disability (QL3) offer all the advantages of the numerical rating
      scale measuring disability in general (QL1) (simple instruction, high
      plausibility for the patients, and simple, fast practicability), but they provide
      more information about the patient's disability, which allows comparisons of
      disability at different times in the therapeutic process. Numerical rating scales
      are not suitable for patients with poor ability to abstract. For these patients
      it is necessary to use a questionnaire which asks concretely about what the
      patient can or cannot do (e. g. RM). Because of its better psychometric
      properties, the QL3 should be favored over the RM.

PMID- 12800013
TI  - [Computer-assisted tool (QUAST) for documentation and quality assurance in pain
      treatment].
AB  - BACKGROUND: In chronic pain patient's diagnostic and therapy planning many
      complex information must be evaluated and analysed. The variety of data cannot be
      mastered without assistance of a database tool adapted to these special need.
      DATABASE ENVIRONMENT: On the base of FileMaker Pro 5.0, a user-friendly and
      analysis-oriented database environment for documentation and quality assurance in
      pain therapy (QUAST) has been developed. QUAST has been tested for 2 years by 23
      pain clinics in Germany including data of more than 14.000 patients. Among
      patients'demographic and clinical data all 335 fields of the validated German
      pain questionnaire are included in QUAST together with psychometric test
      procedures (CES, SES, PDI, SF-36). We developed a outcome questionnaire for the
      evaluation of treatment - related changes of outcome variables (103 fields), a
      daily questionnaire (11 fields) and a protocol to assess the effects of neural
      and other blockades (144 fields). All data of therapy and outcome can be
      documented (total number of the fields: 2661). The test results (e. g. in the
      form of total or compound scores) can be analysed and printed. For pain related
      diagnoses, procedures, blockades, drugs, expected and unexpected events
      hierarchical coding systems (altogether 72,157 data records) have been developed.
      These can be assigned automatically to coding systems like ICD-10 or ICP-M.
      CONCLUSION: Due to its ability of export into other databases and already
      enclosed routines QUAST permits an internal assurance of quality of process and
      outcome in pain management. It also can be an instrument of an external quality
      assurance. QUAST is at present the only computer system available in Germany, to
      fulfil the required prerequisites for adequate quality control.

PMID- 12800014
TI  - [Recommendations for the standardized evaluation and classification of patients
      with painful temporomandibular disorders].
AB  - INTRODUCTION: Due to the considerable degree of variation that exists among care
      providers with respect to the assessment of patients suffering from painful
      temporomandibular disorders (TMDs), an interdisciplinary working group for the
      study of orofacial pain aimed at developing recommendations for the evaluation
      and diagnostic classification of such patients. METHODS: Following an extensive
      literature search (computer-based search and handsearch), several working
      sessions were needed to develop a standardized diagnostic protocol. It was a
      prerequisite that recommended measures and instruments should have acceptable
      reliability and validity. Three independent reviewers - well-known experts in the
      pain field - critically reviewed the contents of our recommendations. RESULTS: A
      two-axis approach is recommended to assess the somatic and psychosocial
      parameters of the pain experience. Our concept closely follows the Research
      Diagnostic Criteria for Temporomandibular Disorders. In addition, we distinguish
      a minimal, a standard, and an extended evaluation. CONCLUSIONS: The
      recommendations appear to be useful to enhance the diagnostic quality in the
      evaluation of patients with painful TMDs.

PMID- 12800015
TI  - [Pain conference. An example of an interdisciplinary cooperation].
AB  - BACKGROUND: In the interdisciplinary Pain Conference, pain specialists of various
      disciplines discussed - partly in the presence of the concerned patient -
      explanations as to the cause of a specific pain. The following example portrays
      the events of the conference. CASE REPORT: In this case, despite extensive
      diagnostics, no explanation due to an organ failure could be found for a 74-year
      pld man with worsening neurological pain above the knee. The patient's desire the
      change was so strong that after ineffective outpatient care and different
      operations, such as hernitomy, fibroma removal and the implantation of an
      epidural stimulating electrode (SCS), other inpatient pain therapies followed
      using anasthesiological, balneophysical and psychological techniques, as well as
      medications. DIAGNOSIS AND THERAPY: The interdisciplinary discussion, including
      all the various diagnostical findings and the results of the therapeutical
      efforts, lead to the decision by conference participants to use the new
      electrophysical and imaging diagnostics. This lead to the discovery of a
      leiomyosarcoma, which had surrounded the N. obtoratius. After the removal
      surgery, the pain was gone and the pain medications being used could gradually be
      dropped.

PMID- 12800016
TI  - [Not Available].

PMID- 12800017
TI  - [Nociception in newborn and premature babies].
AB  - BACKGROUND: The somatosensory system of preterms and newborns differs
      substantially from adults. These differences are of considerable preclinical and
      clinical interest. Maturation of A- and C-fibre synaptic connections in the
      dorsal horn and development of descending inhibition from the brainstem all take
      place postnatally in the rat. In early stages of development there is no definite
      spatial separation in the dorsal horn between the nociceptive and the non
      nociceptive system. In preterms but not in adults non-noxious stimuli can induce
      central sensitization. Many neurotransmitters and signalling molecules involved
      in pain pathways are expressed early in the developing nervous system but do not
      reach adult levels for a considerable period. More important, receptors are
      frequently transiently overexpressed or expressed in areas during development
      where they are not seen in the adult and may have a different functional profile.
      The descending pain inhibitory system that provides an important protection
      against central sensitization develops later than the ascending nociceptive
      system. Thus, during a critical period of time the immature nociceptive system is
      highly vulnerable. For example, neonatal circumcision in the absence of analgesia
      results in increased pain responses during subsequent routine vaccination months
      later. CONCLUSIONS: In view of the changing nature of neonatal somatosensory and
      pain pathways and the vulnerability of the developing nervous system to
      alterations in sensory stimulation it is important that preterms and newborns
      need the care of a specialist for prevention and treatment of pain to avoid
      suffer and long-term changes in the nervous system.

PMID- 12800018
TI  - [Assessment and measurement of pain].
AB  - BACKGROUND: The assessment and measurement of pain is essential in the
      implementation and control of pain relieving strategies. The measurement of pain
      in infants and children should be based on the consideration of age, cognitive
      level, psychological status, intercurrent diseases and the social context in
      order to register the child's individual situation and to avoid
      misinterpretation. DIAGNOSIS: In the preverbal infant, behavioral and
      physiological cues have to be interpreted by the caregivers. For the assessment
      of pain in children of four and older who have at least a basic understanding of
      the pain concept self assessment methods (as rating scales, specific pain
      interviews, diaries and questionnaires) can be used. In any case the instruments
      used should be age appropriate. The instruments used for the different age groups
      are presented with comments on quality and clinical applicability.

PMID- 12800019
TI  - [Psychological interventions for acute pain in childhood].
AB  - BACKGROUND: Pain sensation depends on individual anxiety and situational
      circumstances. It is attributed a psychological and social basis. In children,
      the sensation of pain generally exceeds its perception. ACUTE PAIN IN CHILDHOOD:
      Facing acute pain in childhood - especially during medical procedures -,
      interventions derived from behavioural medicine may help minimize the sensation
      of fear and pain as well as maximize the experience of internal control. But, it
      is impossible to totally eliminate acute pain that way. Although it is undisputed
      that children benefit from psychological intervention, in clinical practice its
      potential is largely underestimated. Factors with impact on the sensation of
      acute pain and resulting behavioural and coping strategies are presented. The
      psychological preparation for a painful medical procedure is demonstrated in
      detail as an example of a behavioural medicine derived procedure.

PMID- 12800020
TI  - [Pediatric nursing in pain therapy].
AB  - KEY POSITION: Pediatric nursing owns a key position in pain therapy, due to its
      patient centered tasks and special kind of labor repartition between medicine and
      nursing. However, it is to admit that this key position obtains various forms of
      appearance in the different settings of pediatric nurses's practice. PAIN
      QUESTIONNAIRES: The difficulties within the correct assessment of children's pain
      by nurses refer to the application of valide pain questionnaires and continuous
      documentation. A prototype of pain prevention in nursing is the 'minimal
      handling' concept. Effective psychologic measures of pain prevention and relief
      are not only intrinsic and extrinsic focussing of awareness but also just holding
      the patient's hand. 'Cutaneous stimulation' and 'counterirritation' should be
      mentioned as physical techniques. COPING ABILITY: Close contact with friends or
      parents is one of the most important factors enhancing the patient's coping
      ability. If confronted with their own child in pain, parents often feel helpless
      which may result in anxiousness, overprotection, and inadequate support. Thus
      both parents and children need professional training to face painful procedures
      and behave in a supportive manner. There are numerous non-medical techniques
      which either by themselves, or in combination with analgetics, have the potential
      to substantially add to quality of life of the paediatric patient in pain.

PMID- 12800021
TI  - [Pain therapy in acute pediatric diseases and vaccination].
AB  - PHENOMENON PAIN: While pain is one of the main reasons for an unscheduled visit
      to the paediatrician, pain due to painful procedures is of major importance in
      scheduled visits. Actual pain therapy is illustrated in the treatment of burns.
      Incomplete analgesia may have an unfavourable impact on morbidity and mortality.
      The pain score does not correlate with the extent of the burned area, and is
      regularly underestimated. General anaesthesia or analgo-sedation are warranted
      during the care of the burned patient. INSUFFICIENT ANALGESIA: Consequence of
      insufficient analgesia during primary care is an increased need of analgesics,
      and an increased pain treatment failure rate during subsequent procedures. Pain
      is interfering with anxiety, sleep disturbances and post-traumatic psychologic
      alterations. All those symptoms must be treated adequately. ACUTE ILLNESS AND
      INJECTIONS: This article covers pain from otitis media, pharyngitis, Guillain
      Barre syndrome, purpura fulminans, Toxic Epidermal Nekrolysis, as well as the
      usage of local anaesthesia during injections, not to forget the application of
      non-pharmacologic methods for pain therapy and prophylaxis.

PMID- 12800022
TI  - [Painful diagnostic and therapeutic interventions].
AB  - BACKGROUND: There are many modes to prevent pain during minor surgical procedures
      or painful interventions. THERAPY: Besides mental preparation and support there
      are various effective locoregionalanalgetic and sedative regimens from (analgo
      )sedation to total anaesthesia adequate for age. CONCLUSIONS: If safety rules are
      followed and medical indication is adequate, the presented regimens are safe and
      effective tools with respect to stress prevention in the discussed field. There
      are many modes to prevent pain during minor surgical procedures or painful
      interventions. THERAPY: Besides mental preparation and support there are various
      effective locoregionalanalgetic and sedative regimens from (analgo-)sedation to
      total anaesthesia adequate for age. CONCLUSIONS: If safety rules are followed and
      medical indication is adequate, the presented regimens are safe and effective
      tools with respect to stress prevention in the discussed field.

PMID- 12800023
TI  - [Management of postoperative pain in children].
AB  - TREATMENT OF PAIN: Undertreatment of postoperative pain in children is a problem
      in clinical practice. This is due to a lack of both knowledge about age-specific
      aspects of physiology and pharmacology, and routine pain assessment. For example,
      the fear of side-effects prevents the adequate usage of opioids. It is of major
      importance to select a route of drug administration where the child feels
      comfortable with (avoid intramuscular injections). NON-OPIOID ANALGESICS: Non
      opioid analgesics are recommended for basic pain treatment after minor surgical
      procedures. Instead of using the whole multitude of drugs available, the doctor
      should stick to those drugs he is familiar with (acetaminophen, ibuprofen,
      diclofenac, dipyrone). OPIOIDS: Opioid usage requires individual dose titration
      and careful monitoring of side-effects (respiratory monitoring, sedation score).
      The strong opioids piritramide and morphine may advantageously be administered as
      either continuous, or patient-controlled iv- infusion (PCA). FORMS OF THERAPY: In
      addition to infiltration anesthesia, intraoperatively applied nerve blocks
      provide excellent pain relief. Epidural analgesia with local anesthetics and/or
      opioids via a thoracic or lumbar epidural catheter is a therapeutic option after
      thoracic or abdominal surgery, or after extensive orthopedic or urological
      interventions. Adjuvant analgesics and nonpharmacologic interventions, i. e.
      transcutaneous electrical nerve stimulation (TENS), are primarily indicated in
      patients suffering from neuropathic pain. CONCLUSION: The establishment of pain
      services and the comprehensive education of both the nursing and the medical
      staff should help to improve postoperative pediatric pain therapy.

PMID- 12800024
TI  - [Musculoskeletal pain].
AB  - BACKGROUND: In paediatrics, numerous diseases present with the leading symptom of
      muscular, articular, or bone-related pain. The pain as such is seldom diagnostic
      with regard to pain etiology. Regularly, the significance of inflammatory as well
      as non-inflammatory pain is underestimated. CLASSIFICATION OF MUSCULOSKELETAL
      DISEASES: We present 4 case reports, illustrating the classification of
      musculoskeletal diseases into 4 main groups, being the basis for the modelling of
      disease, and pain treatment. THERAPY: Pain therapy is either symptomatic or based
      on specific pathophysiology. Pain therapy consists of the moduls analgesics,
      antiphlogistics, physiotherapy, psychosocial support, and complementary
      therapies. We give advice on differential therapy. A transparent team-oriented
      concept comprising physicians, physiotherapists, ergotherapists, psychologists,
      and social workers is the basis for any successful long-term therapy. Regular
      outpatient visits in consent with the family doctor are mandatory as are
      education and treatment periods on ward. We encourage our patients to join formal
      self-supportive patient groups.

PMID- 12800025
TI  - [Recurrent abdominal pain].
AB  - BACKGROUND: Recurrent abdominal pain is found in 10-25% of school-aged children,
      thus being one of the most frequent complaints in childhood. Despite that, our
      knowledge about this syndrome is still very incomplete. DIAGNOSIS AND THERAPY: In
      the majority of cases, the traditional diagnostic approach understanding
      abdominal pain as a symptom of an underlying organic or psychological disease
      does not lead to a well-defined diagnosis with straightforward therapy. The
      natural course of abdominal pain in childhood seems to be less favorable than
      often assumed. Modern biopsychosocial models of recurrent abdominal pain are
      presented as a basis for future multimodal therapeutic concepts.

PMID- 12800026
TI  - [Therapy of headaches in childhood and adolescence].
AB  - BACKGROUND: Headaches are one of the most common health problems of children and
      adolescents, afflicting between 50-90% of the pediatric population in some form
      sometimes during their first two decades of life. Due to changing prevalence
      rates, more or less complex classification systems, inconsistent therapy
      responses with great inter- and intraindividual variabilities and high placebo
      response rates, pediatric headache syndromes are frequently thought to be too
      difficult for the outpatient evaluation and treatment in clinical practice.
      THERAPY AND PROGNOSIS: However, with the introduction of the International
      Headache Society classification system, the continuously expanding knowledge
      about the pathophysiology of different headache syndromes and the development of
      new symptomatic as well as causative treatment options - covering both:
      pharmacologic and non-pharmacologic approaches - a pragmatic diagnostic work up
      and the development of specific treatment schedules for pediatric headache
      patients is now possible.

PMID- 12800027
TI  - [Psychological descriptors of excessive use of analgesic medication].
AB  - INTRODUCTION: Patients suffering from migraine and tension-type-headache are at
      risk of misusing analgesics and therefore developing chronic drug-induced
      headache. The present study compares migraine patients with and without abuse to
      identify psychological descriptors promoting drug abuse. METHODS: We examined 21
      in-patients with migraine and drug-abuse and 21 out-patients with migraine and no
      drug-abuse who were comparable regarding age and diverse pain variables
      (intensity, frequency, duration, etc. ). Psychometric questionnaires measured the
      constructs "pain-", "depression", "self-efficacy" and "pain-coping". Using a
      standardized interview we investigated the external (environment) and internal
      (mental factors) conditions of all patients during medication intake. RESULTS:
      Migraineurs who misused medications showed significantly greater disability,
      greater helplessness and anxiety due to pain and a tendency towards more marked
      general depression than non-abusers. The extent of the helpless and depressive
      coping with pain was best suited for distinguishing the patients with and without
      drug abuse, followed by the fact that those with abuse receive drugs from several
      doctors at the same time and demand that the drugs free them of all complaints.
      CONCLUSIONS: These findings suggest that migraine patients with drug abuse often
      take analgesics not according to their headache, but rather depending on certain
      other factors.

PMID- 12800028
TI  - [Structure quality of independent physicians for pain management--is there a
      standard?].
AB  - BACKGROUND: Evidence based standards for structure quality in out-patient
      management of chronic pain states do not exist. Therefore we tried to evaluate if
      german standards for outpatient management of chronic pain states which are based
      on opinions of experts for pain management influence the outcome quality of
      independent physicians for treatment of chronic low back pain. METHODS: 35
      independent physicians, selected on a voluntary basis from 2100 physicians of a
      bavarian greater district with 1,6 Mio. inhabitants, and one outpatient treatment
      facility for pain patients of the university of Erlangen-Nuremberg have been
      evaluated by questionnaires. Questions examined certain structural conditions of
      the treatment facility as compared to german guidelines for outpatient treatment
      of pain patients ("Schmerztherapievereinbarung"). 157 patients suffering from
      chronic low back pain documented before and after a treatment interval of 6
      months their pain intensity during the last 24 hours (numeric rating scale), the
      interference of pain with daily living (german version of the Brief Pain
      Inventory) and their quality of life (SF-36). Pre-post changes have been used as
      parameters for outcome quality. RESULTS: Neither baseline data nor pre-post
      differences of outcome parameter did correlate significantly with the scores of
      structure quality (17-71% of maximum) of the treatment facilities. However,
      multimodal therapy programs have not been used for pain management. CONCLUSIONS:
      Structural indicators of german guidelines for outpatient treatment of pain
      patients ("Schmerztherapievereinbarung") are not sufficient to improve outcome
      quality of patients with chronic back pain. Multimodal therapy programs have been
      shown to be effective in chronic back pain and should be implemented in the
      guidelines.

PMID- 12800029
TI  - [MIDOS--validation of a minimal documentation system for palliative medicine].
AB  - INTRODUCTION: Repeated assessment of pain and other symptoms is required for
      quality assurance in palliative care. However, physical and cognitive impairment
      of the patients may impede the use of standardized questionnaires and
      documentation systems in palliative care setting. We developed a minimal
      documentation system (MIDOS) for the specific requirements in this setting.
      METHODS: The German versions of the Brief Pain Inventory (BPI) and the quality of
      life questionnaire SF-12 were completed for all patients admitted to the
      palliative care unit. Cognitive impairment was assessed with the Mini Mental
      State Examination (MMSE). With admission as well as on subsequent consultations
      patients self-assessed average and maximum pain intensity on numeric rating
      scales and the intensity of drowsiness, nausea, constipation, dyspnea, weakness,
      anxiety and well-being on verbal categorical scales. RESULTS: From August 1998 to
      June 1999 128 patients were documented consecutively. Fifty-nine percent of these
      patients were treated with WHO-step 3 opioids. Cognitive impairment (MMSE<24) was
      present in 37% of the patients. Self-assessment with MIDOS was possible for 114
      patients at the time of admission, and for 108 patients at the end of therapy.
      Pain, drowsiness and weakness were documented by most patients, whereas the other
      symptoms were reported less frequently. DISCUSSION: Factor analysis showed one
      factor for pain and two factors for the other symptoms. The pain sum score of
      MIDOS correlated with the factors of the BPI, the symptom sum score of MIDOS
      correlated with the factors of the BPI and the mental sum score of the SF-12,
      though on a lower level. MIDOS sum scores showed good pain relief and symptom
      control for patients discharged home or to other services, whereas the symptom
      sum score gave an indication of the deterioration in the terminal phase for those
      patients who died during in-patient treatment. Test-retest stability was good for
      a subgroup of patients with stable opioid doses. CONCLUSIONS: We conclude that
      MIDOS is a valid instrument for self-assessment of the patient's symptoms and may
      be used to monitor the efficacy of symptom management.

PMID- 12800030
TI  - [Potential limitations and risks in the treatment of painful neuropathies].
AB  - INTRODUCTION: Neuropathic pains often cause social disintegration of the
      patients, encouraging us to apply microsurgical techniques to peripheral nerve
      lesions, but there are limitations and risks to take into account when handling
      scarred nerve tissue. FACTS AND THEORETICAL CONSIDERATIONS: The historical
      development of our microanatomical knowledge of grading of nerve lesions as well
      as facts on different fibrotic intraneural reactions are pointed out and
      additionally compared to today's theories of the origin of neuropathic pains.
      METHODS: The microsurgical methods applied to entrapment syndromes, pseudoneuroma
      and neuroma formations consist of either external and interfascicular neurolysis
      or nerve grafting depending on the estimated grade of nerve lesion. If we
      primarily don't try to restore motor function after a nerve lesion but intend to
      achieve reduction of neuropathic pain due to a scarred nerve, the well-known
      methods of neuromodulation or thermic/cryoneurotomy increasingly become the
      treatment of choice. CONCLUSIONS: There is no real mental connection existing
      between our successful microsurgical methods on restoration of nerve function and
      the theories of the origin of neuropathic pains. We do treat pain of nociceptive
      origin by means of neurolysis but have abandoned these methods more and more in
      the case of chronic neuropathic pain. But on the other hand, the neuromodulation
      and neurotomy methods preferred in these cases still have limitations in
      compatibility and success rates. In a few cases we even risk inducing or
      worsening chronic neuropathic pains by means of microsurgery and/or neurotomy of
      a lesioned nerve.

PMID- 12800031
TI  - [Differential diagnosis and therapy of headache in HIV infection].
AB  - HEADACHE AND HIV INFECTION: Headache is one of the most common pain syndromes in
      HIV infection. The prevalence of headache in HIV infected patients in the
      published cross-sectional and longitudinal studies is between 3.8% and 47.4%
      depending on the study methodology and the study subpopulation. In this review,
      we analyse these cross-sectional and longitudinal studies and the case reports of
      headache in HIV infection. Both primary headache, such as migraine or tension
      type headache, and secondary headache, e. g. caused by opportunistic infections
      or neoplasms, can be observed. In addition, there is a so-called "HIV headache"
      which develops de novo during the HIV infection, the cause of this headache type
      is still unclear. Migraine shows an amelioration during the course of the HIV
      infection whereas tension-type headache shows a deteriotation. In some patients,
      however, tension-type headache cannot be differentiated from HIV-headache.
      THERAPY: The therapeutic management of headache during the HIV infection is the
      same as in non-infected subjects. However, tricyclic antidepressants and steroids
      as headache prophylactic agents are often more effective than in non-infected
      subjects and should be prescribed more generously. Some pharmacological
      interactions have to be considered, e. g. NSAID might increase the toxicity of
      antiretroviral substances.

PMID- 12800032
TI  - [Placebo].
AB  - BACKGROUND: The placebo reaction is a widely known phenomenon but the way it
      develops is not fully understood. This fact has given rise to numerous
      misinformed opinions on this subject. PLACEBO ANALGESIA: More research has been
      done in the field of placebo analgesia, where the involvement of the endogenous
      opioid systems was discovered some twenty years ago. Recently there have been
      some new discoveries concerning the role of expectancy and drug conditioning in
      experimentally induced placebo analgesia. PLACEBO REACTION: The placebo reaction
      is very impressive not only following drug administration, but also after
      surgical operations. In many cases, it is extremely difficult to decide whether a
      therapeutic success is due to a given medical intervention or to a placebo
      response. The use of placebo controlled clinical studies remains an ethically
      charged issue.

PMID- 12800033
TI  - [MIDOS--an electronic database for the palliative care unit].
AB  - INTRODUCTION: A minimal documentation system (MIDOS) has been developed for self
      assessment of pain and other symptoms by the patients on palliative care units.
      To decrease the administrative burden and thereby increase the acceptance of the
      system an electronic database was developed to facilitate data entry and
      documentation. SYSTEM: The database is based on Microsoft Access. Screen masks
      are used for navigation and data entry. According to the type of data items may
      be chosen in checklists or pull-down menus or entered as free text. The main menu
      documents personal data from the patient. Submenus can be reached from the main
      screen mask. Submenus included are the core documentation of the working group of
      the German Ministry of Health, the German versions of the Brief Pain Inventory,
      the quality of life questionnaire SF-12 and the Mini Mental State Examination for
      assessment of cognitive impairment. Data from these instruments may be assessed
      repeatedly for the same patient. Documentation of follow-up consultations include
      self-assessment of pain and other symptoms by the patient (MIDOS) and the
      analgesic regimen. These informations should be documented for each consultation.
      CONCLUSION: This data base was used in two trials on the palliative care unit of
      the university of Cologne, confirming data safety and convenience of the
      programme. We recommend the use of this data base in combination with MIDOS and
      the core documentation for routine assessment on the palliative care ward.

PMID- 12800034
TI  - [Therapy of the acute migraine attack and migraine prophylaxis. Recommendation of
      the "Deutsche Migrane- und Kopfschmerz-Gesellschaft].

PMID- 12800035
TI  - [Not Available].

PMID- 12800036
TI  - [Patient-controlled analgesia: psychological predictors of pain experience,
      analgesic consumption and satisfaction].
AB  - INTRODUCTION: The present study examines the relationship between different
      psychological variables (including anxiety, depression, locus of control,
      expectations of pain intensity and social support) and postoperative pain,
      analgesic consumption and satisfaction with the pain management in a study sample
      of 67 patients. METHODS: Intravenous patient-controlled analgesia was used for
      postoperative analgesia. Pain intensity was assessed by numerical rating scales
      and obtained from the PCA-report. On the fourth day after surgery, the patients
      estimated retrospectively the pain intensity of the first day. RESULTS: The
      results show that postoperative pain experience correlates significantly with
      several variables raised preoperatively. The retrospective variables were
      predicted by psychological measures. There was no relationship to the pain
      measurements of the PCA-report. CONCLUSIONS: While pain experience could be
      predicted by stable psychological traits, satisfaction was associated with the
      state variables, like anxiety and depression. It is precisely satisfaction with
      the pain therapy that could be improved by special preoperative psychological
      training and/or general information about the postoperative pain intensity.

PMID- 12800037
TI  - [Outcome quality of treatment for chronic low back pain under primary care
      conditions].
AB  - BACKGROUND: Little is known about the outcome quality of treatment for chronic
      low back pain under primary care conditions in Germany. METHODS: All physicians
      (2100) of middle Franconia, a region of Bavaria with 1.6 million inhabitants,
      involved in outpatient management were asked to include consecutively patients
      who suffered from low back pain of at least 4 weeks duration without decreasing
      intensity. Before and after a 6-month interval patients documented the following
      outcome data in a questionnaire: pain intensity during the last 24 hours
      (numerical rating scale), pain-dependent disability (Brief Pain Inventory, German
      version), health-related quality of life (SF-36, German version), depression
      (Allgemeine Depressionsskala), pain chronification state (Mainz Pain Staging
      System) and the days of inability to work within 3 months before start and end of
      the interval. Treatment of patients was not standardized and included the natural
      spectrum of non-surgical therapies for low back pain except multimodal pain
      therapy programs. RESULTS: Thirty-five physicians participated in the study.
      "Before and after" data of 157 patients (43+/-12 years) could be analysed.
      Initially 20% were classified in pain chronification state I, 57% in state II and
      23% in state III. The pain intensity, pain-dependent disability, depression and
      quality of life improved significantly but mean differences and effect sizes were
      small (p<0.41). Less than one third of patients improved by 30% or more from
      baseline or by one step in the chronification state of pain. Days off work did
      not change significantly. Predictors for positive therapy response could not be
      identified. CONCLUSIONS: Monodisciplinary treatment procedures are not sufficient
      to ameliorate problems of patients in advanced chronification states of back
      pain.

PMID- 12800038
TI  - [Diagnostic criteria and new classification of the cervical spine syndrome].
AB  - OBJECTIVES: Pain and functional disorders of the neck are widely diagnosed as
      "cervical spine syndrome". As this diagnosis is not able to sufficiently specify
      the different symptoms, a new classification with five pain syndromes, created
      empirically, was developed. The aim of this study is to evaluate the predictive
      values of the diagnostic criteria respectively clinical findings of patients
      diagnosed with cervical spine syndrome. METHODS: Within the two year time frame
      of the study all patients diagnosed with "cervical spine syndrome", which
      presented themselves at the clinic, were included. The statistic analysis was
      performed in multiple steps: univariate analyses, bivariate variable screening
      and the use of the logistic regression model. RESULTS: Within two years 653
      patients previously diagnosed as suffering from cervical spine syndrome presented
      at the clinic; 332 of them were included in the study. According to the
      diagnostic criteria they were attached to one of the five pain syndromes. The
      statistical analysis showed in 17 of 35 evaluated diagnostic criteria a
      significant association to one of the five subgroups of the cervical spine
      syndrome. CONCLUSION: The statistical analyses revealed significant associations
      between diagnostic criteria which were assessed by clinical examination and the
      five subgroups of the cervical spine syndrome. The identified predictors
      represent the typical syndrome-associated diagnostic criteria of a certain
      syndrome-subgroup.

PMID- 12800039
TI  - [Treatment of chronic pain with drug addicts].
AB  - BACKGROUND: The therapy of chronic pain of primarily drug addicted patients is a
      problem which has hitherto remained unresolved within the field of pain therapy.
      Synergistic effects of the prescribed medicine with additionally taken drugs or
      medicine which can lead to an unpredictable increase of effect of prescribed
      opioids are of special significance. When addiction and pain appear
      simultaneously medical aspects of the syndrome of addiction have to be
      implemented within the framework of coordinated therapy. In this case regular
      controls are to be taken; at the same time the treatment of cases of relapse must
      occur gradually. Not only is the final aim of this therapy abstinence but also a
      survival as healthy as possible. We don't ask more of the patient as he is able
      to perform, but we do ask everything which can be expected of him. In a treatment
      contract both therapist and patient agree on their individual tasks. With
      exemplary cases both the case history and the course of the therapy of four
      patients with simultaneous symptoms are illustrated. DISCUSSION: It becomes clear
      that the cooperative concept of therapy both with regard to pain as to addiction
      render an individual weighing of risks necessary. If the treatment of chronic
      pain is to be regarded as a primary goal then addicts can be treated in an
      institution devoted to the treatment of pain, providing there is a functioning
      cooperation with colleagues who are experienced in the treatment of addiction.

PMID- 12800040
TI  - [No addiction in pain patients? Questions of a reading physician].
AB  - INTRODUCTION: In some recent German textbooks of pain management there is
      maintained that psychological dependence to opioids in pain patients is not a
      real problem. The evidence for this statement is reviewed. METHODS: Reading of
      the cited literature and additional MEDLINE search. RESULTS: Not a single
      convincing clinical study could be found in the references to proof the claimed
      absence of addiction in pain patients. The central topics of some papers cited
      had not been taken into account, other papers have been cited distorting their
      meaning or overemphasizing their true importance. CONCLUSIONS: Despite the
      assertion of the contrary, the maintenance of no addiction in pain patients,
      especially in noncancer pain, seems to be not yet proven.

PMID- 12800041
TI  - [Medical treatment of rheumatoid arthritis].

PMID- 12800042
TI  - [The Bier block as an experimental tool to differentiate peripheral and central
      effects of analgesics on people].
AB  - AIMS: In this study the technique of intravenous regional anesthesia (Bier block)
      was evaluated as an experimental tool to differentiate peripheral and central
      effects of analgesics. METHODS: Touch and pain thresholds were assessed under
      control conditions and during a prolonged Bier block. In addition, models of
      experimental pain and hyperalgesia were used (Capsaicin injection, histamine
      iontophoresis, pinch). RESULTS: No signs of impaired function of Adelta- und C
      fibers were found during a Bier block of up to 30 min after onset of ischemia. In
      contrast, Abeta-mediated touch sensation declined significantly. On the basis of
      these results, peripheral mechanisms of action could be verified for low-dose
      lidocaine and for morphine in the Bier block setting. CONCLUSIONS: The Bier-block
      setting can be successfully employed to differentiate peripheral and central
      modes of action of analgesics.

PMID- 12800043
TI  - [Health care utilization in patients with Fibromyalgia Syndrome (FMS)].
AB  - BACKGROUND: The purpose of the study was to examine the pain related health care
      utilization in patients with fibromyalgia syndrome. METHODS: In a multicenter
      study six rheumatological hospitals associated in the rheumatological center of
      Heidelberg participated. All consecutive patients which fulfilled the ACR
      criteria of fibromyalgia were assessed. Data about pain and related treatments
      were available from n=259 patients. RESULTS: Patients suffered from chronic
      generalized pain on average for 5 years before being diagnosed as fibromyalgia.
      In most of the cases longlasting localized pain symptoms preceeded generalized
      pain. The spectrum of pain related treatments seems to be wide and arbitrary: 87%
      took questionable or excessive medication. 86% had some form of physiotherapy and
      41% already experienced psychological treatment. 28% of the patients consulted
      dental surgeons including teeth extraction and 20% underwent multiple orthopaedic
      surgery. A mean of five different health care professionals were consulted
      regarding the pain problem. Treatment satisfaction rated by the patients was
      lowest with pharmacological and highest with psychological treatment and
      physiotherapy. CONCLUSIONS: The health care-seeking behavior of fibromyalgia
      patients seems to be characterized by a multitude of different treatment
      attempts. Treatment was often invasive and focused on localized symptoms rather
      than on the generalized pain syndrome. An early confirmation of the diagnosis and
      a more evidence based treatment is strongly indicated.

PMID- 12800044
TI  - [Epidemiology of chronic pain - an investigation in 5 medical practices].
AB  - BACKGROUND AND METHODS: The aim of this study was to get more information about
      the prevalence of chronic pain in different practices of home physicians. 900
      patients of five different specialists (general medicine, internal medicine,
      neurology, orthopaedics, surgery) in the german town Bochum were investigated
      with a questionnaire about chronic pain. Chronic pain was defined as a continuous
      or intermittend pain of longer duration than six months. RESULTS: 36% (328
      patients) of all investigated patients had chronic pain due to this definition,
      twice more women than men. The four most frequent localisations of chronic pain
      were the back, the head, the joints and the legs. 15% of the patients with
      chronic pain were retired or going to retire due to their chronic pain.
      Orthopaedics were the most frequent physicians visited in the past. Only 5% of
      the patients had a psychological therapy and only 1% were treated in a pain
      clinic. The primary treatment strategies of the chronic pain were physiotherapy
      and drug therapy. 30% of the patients did not have any pain relieve by the past
      treatment strategies. CONCLUSION: Patients with chronic pain are a frequent and
      important problem in practices of home physicians. The high frequency of patients
      with chronic pain in practices of specialists demonstrates the necessity of a
      special qualification also on this level of our medical system.

PMID- 12800045
TI  - [A prospective double blind study of cervical nerve infiltration with isotonic
      saline and local anaesthetic].
AB  - PURPOSE OF THE STUDY: Aim of this investigation was the examination of the
      therapeutic effect of cervical nerve infiltration with mepivacaine in comparison
      to local applications of isotonic sodium chlorid solution in a prospective
      randomised double blind study. METHODS: 57 patients with cervicocephalgia or
      cervicobrachialgia were injected daily with mepivacaine ( n=28) or physiological
      sodium chlorid solution ( n=29). The success was judged through the blinded
      patients and blinded therapists first after three days of treatment. If no
      improvement occurred a single injection of mepivacaine and triamcinolonacetonid
      was given. This injection could be repeated if required. At the end of the
      inpatient treatment, after a mean of 14 days, the patients assessed the treatment
      according to a scale of 1-4 (painfree - no improvement). RESULTS: The average
      therapeutic effect, in the subjective appraisal of 1-4 by the patients, was 2.15
      in the mepivacaine-group and 2.54 in the sodium chlorid - group. In the
      mepivacaine-group no pain (note 1) was achieved two times and 21 times a clear
      improvement (note 2), while in the sodium chlorid - group 18 times a clear
      improvement was achieved and never freedom of pain ( p<0,038). In the mepivacaine
      group twice a steroidinjection was required, while in the sodium chlorid - group
      this was necessary in 16 cases ( p<0,01). CONCLUSION: Cervical injections with
      mepivacaine improve the subjective pain perception in cervicocephalgia and
      cervicobrachialgia significantly better than isotonic sodium chlorid - solution
      in short term results and can therefore be prefered. After an inpatient treatment
      good and excellent subjective results could be achieved in a high percentage.

PMID- 12800046
TI  - [The implementation of ICD-10 in Germany - tools and information on the
      Internet].
AB  - ICD-10 was implemented for morbidity coding in Germany in January 2000. The
      electronic versions of ICD-10 are introduced. For everyday work with the
      classification and for epidemiological research further tools are provided by
      DIMDI: ICD-10 meta files, ICD conversion tables, ICD-10 thesaurus of diagnostic
      terms. All files are available free of charge via the INTERNET.

PMID- 12800047
TI  - [Psychosocial aspects of chronic low back pain].
AB  - In many patients with chronic low back pain, no close correlation is found
      between the objective physical impairment and the subjective intensity of pain or
      the resulting disability. The process of chronification is the result of a
      complex interaction between somatic and psychosocial factors, as many
      epidemiologic and clinical studies could proof. DISCUSSION: Currently, these
      results are still neglected in clinical practise of diagnosis and therapeutic
      concepts.

PMID- 12800048
TI  - [Medical prohibition of pain therapy in cancer patients - an incredible case
      report].
AB  - CASE REPORT: Case presentation of a 59-year old female patient, who has been
      treated for her cancer by a physician of internal medicine with peroxodisulphuric
      acid. For this therapy to be successful - according to the physician - all drugs
      especially the analgetics had to be stopped. DISCUSSION: Along with this case
      presentation the statement by the German Medical Association is shown and legal
      assessment is discussed.

PMID- 12800049
TI  - [Not Available].

PMID- 12800050
TI  - A synthesis of what we know about the use of physical restraints and seclusion
      with patients in psychiatric and acute care settings: 2003 update.
AB  - PURPOSE: This article is an update of the January 19, 2000, Volume 7, Number 2
      article of the synthesis of research findings on the use of restraint and
      seclusion with patients in psychiatric and acute care settings. CONCLUSIONS: The
      little that is known about restraint/seclusion use with these populations is
      inconsistent. Attitudes and perceptions of patients, family, and staff differ.
      However, all patients had very negative feelings about both, whether they were
      restrained/secluded or observed by others who were not restrained. The reasons
      for restraint/seclusion use vary with no accurate use rate for either. What
      precipitates the use of restraint/seclusion also varies, but professionals claim
      they are necessary to prevent/treat violent or unruly behavior. Some believe
      seclusion/restraint is effective, but there is no empirical evidence to support
      this belief. Many less restrictive alternatives have been tested with varying
      outcomes. Several educational programs to help staff learn about different ways
      to handle violent/confused patients have been successful. IMPLICATIONS: Until
      more is known about restraint/seclusion use from prospective controlled research,
      the goal to use least restrictive methods must be pursued. More staff educational
      programs must be offered and the evaluation of alternatives to
      restraint/seclusion pursued. When seclusion/restraint is necessary, it should be
      used less arbitrarily, less frequently, and with less trauma. As the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO) and the Health
      Care Financing Administration (HCFA) have prescribed, "Seclusion and restraint
      must be a last resort, emergency response to a crisis situation that presents
      imminent risk of harm to the patient, staff, or others" (p. 25) [99A].

PMID- 12800051
TI  - Breast cancer risk perception and surveillance: an integrative review.
AB  - PURPOSE: A family history of breast cancer has taken on new meaning with the
      advancement of genetic technology and the discovery of genes related to breast
      cancer risk. The purpose of this review is to summarize and synthesize current
      literature on breast cancer risk perception and mammography screening practices
      as related to women who have a first-degree relative with breast cancer.
      CONCLUSIONS: Research has shown that women tend to overestimate their breast
      cancer risk and that risk counseling fails to have a significant effect.
      Inconsistent findings exist in relation to the effect of family history on
      screening behaviors and conflicting evidence in the relationship between risk
      perception and mammography use. IMPLICATIONS: Inaccurate risk perceptions for
      high-risk women may be because of the inconsistent messages women are hearing in
      the media or from health care providers in regard to the efficacy of mammography.
      Practitioners need to be careful not to assume that a strong family history of
      breast cancer leads to increased perceived risk, which in turn promotes increased
      mammography use.

PMID- 12800052
TI  - Neonatal pain management with oral sucrose: 2003 update.

PMID- 12800054
TI  - Tesaglitazar AstraZeneca.
AB  - AstraZeneca (formerly Astra) is developing tesaglitazar, a peroxisome
      proliferator-activated receptor (PPAR) agonist, for the potential treatment of
      diabetes and insulin resistance [275466], [377656]. Early phase clinical trials
      for both of these indications were ongoing in July 2002 [459440].

PMID- 12800053
TI  - Novel neutrophil elastase inhibitors as a treatment for neutrophil-predominant
      inflammatory lung diseases.
AB  - Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease
      (COPD) and cystic fibrosis (CF) are progressive and frequently fatal disorders,
      which have, at present, few effective therapeutic methods. The pathogenesis of
      these lung diseases is characterized by a neutrophil-predominant inflammation
      associated with excessive release of neutrophil proteases, including neutrophil
      elastase (NE), a terminal pulmonary tissue destroyer. Although precise pathogenic
      mechanisms have been under debate, the NE-mediated severe pulmonary tissue
      damage, based upon the protease-antiprotease imbalance hypothesis, may be a major
      pathogenic determinant of these diseases, in particular COPD. Novel aggressive
      therapeutic approaches to these lung disorders are required, and prevention of NE
      release may be considered as a promising strategy for disease outcome. This
      review mainly focuses upon the pathogenic contribution of NE to these neutrophil
      predominant inflammatory lung diseases, and evaluates the experimental and
      clinical efficacies of the two-types of appropriate small molecular weight human
      neutrophil elastase (HNE) inhibitors: acyl-enzyme inhibitors and transition-state
      inhibitors. While much progress has been made in the investigation of these
      disorders and the contribution of HNE inhibitors, several fundamental questions
      remain to be answered, and so further studies are required.

PMID- 12800056
TI  - TNF inhibitors: a review of the recent patent literature.
AB  - Overproduction of the inflammatory cytokine tumor necrosis factor (TNF)-alpha is
      implicated in a wide range of pathological conditions, including inflammatory
      bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis and stroke.
      This review focuses on recent developments in the patent literature, which are
      aimed principally at the suppression of TNF release. The review will separately
      detail the development of biological agents, such as soluble TNF receptors and
      engineered antibodies, and small molecules, which primarily target TNF.

PMID- 12800055
TI  - Recent chymase inhibitors and their effects in in vivo models.
AB  - Recent efforts to discover novel chymase inhibitors have produced orally
      bioavailable compounds. Studies using such inhibitors have shed light on the
      pathophysiological roles of chymase, eg, a chymase inhibitor has prevented
      atherosclerosis, restenosis and myocardial infarction in respective animal
      models. In these cardiovascular diseases, angiotensin I is likely involved as a
      substrate for chymase. The studies using chymase inhibitors have also shown the
      potential role of chymase in other diseases, including atopic dermatitis, tissue
      fibrosis and rheumatoid arthritis; a chymase inhibitor also reduced ischemic
      reperfusion injury in the small intestine. These results suggest the existence of
      physiological substrates for chymase other than angiotensin I. Chymase inhibitors
      are promising for the treatment of cardiovascular as well as inflammatory
      diseases.

PMID- 12800057
TI  - NBI-6024 (Neurocrine Biosciences).
AB  - Neurocrine is developing NBI-6024 in collaboration with Taisho, as part of
      Neurocrine's altered peptide ligand (APL) program, as a potential treatment for
      type I diabetes. By July 2002, Neurocrine had completed four phase I/II trials of
      NBI-6024 and the compound was in phase IIb studies in Europe and phase Ib studies
      in the US. By October 2002, a second phase IIb trial was scheduled to begin in
      the US later in 2002 or in early 2003.

PMID- 12800058
TI  - Lumiracoxib (Novartis).
AB  - Lumiracoxib, an inhibitor of cyclooxygenase 2 (COX-2), is under development by
      Novartis for the potential treatment of osteoarthritis, rheumatoid arthritis and
      pain. By late December 2000, phase III trials had been initiated and were ongoing
      in December 2001.

PMID- 12800059
TI  - Alzheimer's disease: pathophysiology and pharmacotherapy.
AB  - Alzheimer's disease (AD) is the leading cause of dementia in mid-to-late life,
      and is estimated to afflict approximately 20 million people worldwide. There are
      considerable financial, social and emotional costs associated with the burden of
      caring for patients with AD. Clinically, AD is characterized by an insidious loss
      of memory, associated functional decline and behavioral disturbances. Many
      neurotransmitter systems are also affected; however, degeneration in the
      cholinergic system occurs earlier and more consistently than in other systems. As
      cholinergic function is required for short-term memory function, it is believed
      that the cholinergic deficit in AD is also responsible for much of the short-term
      memory deficit. The cholinergic hypothesis of AD has led to the development of a
      number of strategies to enhance the failing cholinergic neurons and thus the
      neurotransmitter acetylcholine (ACh). In general, appropriate management of AD
      patients with antioxidants, acetylcholinesterase inhibitors (AChEIs) and
      psychotropic agents can slow the progression of the disease, improve cognition,
      and reduce behavioral disturbances, which may enhance patient and caregiver
      quality-of-life and delay nursing home residence.

PMID- 12800060
TI  - TA-CD. Xenova.
AB  - TA-CD (formerly IPC-1010), a cocaine conjugate that stimulates the production of
      antibodies against cocaine, is under development by Xenova (formerly Cantab) for
      the potential treatment of cocaine dependence [176912], [414867], [449997]. The
      vaccine was originally discovered at Stanford University and exclusively licensed
      to ImmuLogic Pharmaceuticals as IPC-1010 [176908]. It was renamed TA-CD when
      ownership was transferred to Cantab [463510], [463511]. By April 2002, a second
      phase IIa dose escalation trial was underway [445298], which was ongoing in
      September 2002 [463866].

PMID- 12800061
TI  - Indisulam. Eisai.
AB  - Eisai and the EORTC are developing indisulam, a sulfonamide which inhibits
      progression from the G(1) phase of the cell cycle, for the potential treatment of
      cancer [338089]. As of January 2001, indisulam was in phase II trials in Europe
      for the treatment of solid tumors, and phase II US studies have been ongoing
      since March 2001 [400862]. In 2001, clinical development of the drug in Japan was
      scheduled to begin in fiscal year 2002 [396633].

PMID- 12800062
TI  - Novel antiepileptic and anticonvulsive therapeutic agents.
AB  - Epilepsy is a broad-reaching central nervous system condition and the underlying
      pathology suggests a number of pharmacological pathways that can be targeted for
      drug therapy. These include ion channel modulation, historically the most
      investigated therapeutic approach, as well as regulation of excitatory and
      inhibitory neurotransmission. A broad range of drugs that act at each of these
      targets has been marketed, and promising new drug candidates are being developed
      constantly. In addition, new drug candidates with novel mechanisms of action are
      beginning to emerge. This review covers patent literature with the indication for
      epilepsy between January 2001 and March 2002, and includes brief overviews and
      backgrounds on currently used anti-epileptic and anticonvulsive drugs.

PMID- 12800063
TI  - KW-2170 (Kyowa Hakko Kogyo).
AB  - The pyrazoloacridone, KW-2170, an alkylating agent and topoisomerase II
      inhibitor, is being developed by Kyowa Hakko Kogyo as a potential treatment for
      cancer [273964], [409111], [422561]. By December 2001, KW-2170 had entered phase
      II trials in the US, following approval for the trial from the FDA, which was
      received in November 2001. At this time, the company planned to extend the phase
      II trials to Australia, Singapore, Taiwan and Costa Rica using data from US phase
      I trials. Accelerated Japanese trials were also planned, and an NDA was
      anticipated for 2006, with non-small-cell lung cancer, prostate cancer,
      colorectal cancer, ovarian cancer and breast cancer as the targets [434794],
      [444539]. By August 2002, Japanese phase I trials had been completed [460177].

PMID- 12800064
TI  - Human immunodeficiency virus and the liver: lessons learned and still to be
      learned.

PMID- 12800065
TI  - Natural history and pathogenesis of human immunodeficiency virus infection.
AB  - In this article, we discuss how human immunodeficiency virus (HIV) infection of
      activated CD4+ cells, expressing the chemokine receptors CCR5 or CXCR4, results
      in severe immunosuppression while evading the immune response. We describe how
      infection through mucosal surfaces or via the parenteral route results in rapid
      spread of the virus throughout the body prior to a vigorous CD8+ cytolytic T cell
      response, resulting in establishment of a viral set point. Data is examined that
      suggests the half-life of HIV virions in circulation is less than 6 hours and
      possibly as short as 30 minutes, whereas that of infected CD4 T cells is on
      average 1 to 1.5 days. We also explain how the rate of viral replication dictates
      the rate at which HIV evades the immune response and the rapidity with which
      resistance to antiviral medications may develop. Lastly, we show how anatomic and
      cellular reservoirs of latent viral pools have made the long-term goal of
      complete virus eradication difficult despite enormous advances in our therapeutic
      armamentarium.

PMID- 12800066
TI  - Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology,
      natural history, and treatment.
AB  - Coinfection with hepatitis B virus (HBV) is common in the human immunodeficiency
      virus-1 (HIV)-infected patient because of shared modes of transmission. HBV does
      not appear to alter HIV disease progression; however, HBV infection is more
      frequent and more severe in the HIV-infected population, emphasizing the
      importance of preventing HBV infection. The goal of anti-HBV therapy is
      prevention of cirrhosis because therapy does not eradicate the hepatic reservoirs
      (cccDNA). The approved therapies-interferon-alfa, lamivudine, and adefovir-each
      have a niche in the treatment of chronic hepatitis B in the HIV-infected
      population, but none has been well-studied in this setting. As new drugs
      currently in clinical trials become available, therapy for chronic hepatitis B
      will enter the promising era of combination therapy.

PMID- 12800067
TI  - GB virus type C/Hepatitis G virus.
AB  - After hepatitis G virus (HGV) and GB virus type C (GBV-C) were independently
      discovered, it was determined that they were two isolates of the same virus. The
      HGV/GBV-C genome sequence and organization are closely related to hepatitis C
      virus. Although HGV/GBV-C infection is common and frequently persists in humans,
      infection has not been found to be associated with any known disease state.
      Because this virus is not associated with acute or chronic hepatitis, most people
      refer to it as GBV-C. GBV-C appears to grow in lymphocytes and not in
      hepatocytes, and presumably this is why the virus does not cause liver disease.
      Recent studies suggest that GBV-C infection in HIV-positive people is associated
      with prolonged survival. In vitro coinfection of human lymphocytes with GBV-C and
      HIV lead to decreased HIV replication. Further understanding of the mechanism(s)
      responsible for this interaction with HIV may provide novel approaches for
      treating HIV and AIDS.

PMID- 12800068
TI  - Hepatitis C virus in human immunodeficiency virus-infected individuals: an
      emerging comorbidity with significant implications.
AB  - As antiretroviral (ARV) therapy has become more effective, hepatitis C virus
      (HCV) infection has emerged as an important cause of morbidity and mortality in
      human immunodeficiency virus (HIV)-infected individuals. HIV alters HCV clinical
      presentation, epidemiology, virology, and pathogenesis compared with HCV
      monoinfected individuals. The incidence of chronic and vertical HCV infection is
      increased, the rate of hepatic fibrosis progression is accelerated, peripheral
      and intrahepatic HCV RNA levels are increased, and end-stage liver disease (ESLD)
      and cirrhosis develop more rapidly in coinfected individuals. Based on these
      observations, combined with the increased efficacy of ARV therapy, several
      societies have recommended the diagnosis and treatment of HCV in coinfected
      individuals. HCV treatment with nonspecific antivirals, pegylated interferon
      alpha (PEG-IFN) and ribavirin (RBV), is more complex in coinfected individuals
      compared with monoinfected individuals because these regimens appear to have
      decreased efficacy and the incidence of complications is increased. Although new
      HCV-specific regimens show early promise in HCV monoinfected individuals, it is
      likely that these agents will be used in combination with nonspecific therapies
      and additional studies will be required to evaluate their efficacy in coinfected
      individuals.

PMID- 12800069
TI  - Hepatotoxicity of nucleoside reverse transcriptase inhibitors.
AB  - Hepatotoxicity is an adverse effect of all available classes of antiretrovirals,
      including nucleoside reverse transcriptase inhibitors (NRTI). A syndrome of
      hepatic steatosis and lactic acidosis has been recognized as a rare, potentially
      fatal complication since the advent of NRTI monotherapy in the early 1990s.
      Today, NRTI remain the backbone of antiretroviral combination regimens, and, with
      the success of current treatment strategies, exposure to two or more of these
      agents may occur over a number of years. Hepatic steatosis and lactic acidosis
      are accordingly being observed more frequently, along with a more recently
      recognized syndrome of chronic hyperlactatemia. These as well as other adverse
      effects of NRTI are mediated by inhibition of human DNA polymerase gamma,
      resulting in mitochondrial dysfunction in the liver and other tissues. Early
      recognition and intervention are essential to avert serious outcomes.

PMID- 12800070
TI  - Toxicity of non-nucleoside analogue reverse transcriptase inhibitors.
AB  - The non-nucleoside reverse transcriptase inhibitors (NNRTI) nevirapine (NVP),
      efavirenz (EFV), and delaviridine (DLV) are increasingly being used to treat HIV
      infection. Studies have shown excellent tolerance and efficacy and less
      development of virological resistance with HIV regimens that include NNRTIs.
      Nevertheless, abnormalities in liver enzymes are common in patients with HIV
      infection, and there are multiple etiologies for these abnormalities, including
      drug toxicity, viral hepatitis, opportunistic infections, and substance abuse. In
      particular, highly active antiretroviral therapy (HAART) can result in
      hepatotoxicity through a variety of mechanisms, such as mitochondrial toxicity,
      lipodystrophy syndrome, and steatohepatitis. The NNRTIs have been most frequently
      implicated in hypersensitivity reactions. NVP-containing HAART regimens may be
      more hepatotoxic than are those with EFV and DLV, at least for the first 6 weeks,
      although the data are still contradictory. Coinfection with hepatitis C and B
      viruses appears to significantly increase the risk of toxicity, and therefore all
      patients should be screened for viral hepatitis prior to commencing HAART. Close
      monitoring of transaminases is suggested in all patients commencing HAART,
      especially those with preexisting liver disease and coinfection with viral
      hepatitis.

PMID- 12800071
TI  - Hepatotoxicity associated with antiretroviral therapy containing HIV-1 protease
      inhibitors.
AB  - Human immunodeficiency virus 1 (HIV-1) protease inhibitors are important
      components of highly active antiretroviral therapy and have had a profound impact
      on the natural history of HIV and AIDS. However, in the era of highly active
      antiretroviral therapy (HAART), drug-induced hepatotoxicity or liver injury has
      emerged as an important potential complication of combination antiretroviral
      therapy, particularly those regimens containing protease inhibitors (PIs). Liver
      injury has been associated each of the six PIs currently approved by the U. S.
      Food and Drug Administration (FDA), most commonly with administration of full
      dose ritonavir (600 mg bid or 400 mg bid with saquinavir). However, this regimen
      has been largely replaced by the use of low-dose ritonavir (</= 200 mg bid) to
      pharmacologically "boost" other PI, such as lopinavir or indinavir, which has not
      been associated with an increased risk of hepatotoxicity compared with other PIs.
      Coinfection with hepatitis C virus (HCV) and B virus (HBV) remains an important
      risk factor for the development of HAART-associated liver injury. Although
      studies indicate that coinfected patients can be safely treated with PIs, such
      patients should be closely monitored. In addition, although unsubstantiated, some
      experts recommend evaluation or treatment, or both, of underlying chronic viral
      hepatitis prior to the initiation of antiretroviral therapy. Further research is
      needed to understand the etiopathogenesis of PI-associated liver injury,
      particularly among patients with hepatitis B or C infection.

PMID- 12800072
TI  - Hepatic manifestations of Jeune syndrome (asphyxiating thoracic dystrophy).
AB  - Asphyxiating thoracic dystrophy, or Jeune syndrome, is an autosomal recessive
      skeletal dysplasia with multiorgan involvement. Most patients develop progressive
      respiratory insufficiency related to the abnormally small thorax and renal
      insufficiency. Other clinical manifestations include cystic lesions of the
      pancreas and retinal abnormalities. Hepatic abnormalities have been described
      both clinically and at autopsy, but the pathogenesis of the liver disease is not
      clear. A patient with Jeune syndrome developed complications because of
      progressive portal hypertension necessitating transplantation. We present a
      discussion of the gross and histopathologic findings in the explanted liver,
      along with a review of the pathology of liver disease in Jeune syndrome.

PMID- 12800074
TI  - [The mycota-confusion: commentary on the discussion mycota-immunological
      background of the chronic rhinosinusitis with or without polyposis].

PMID- 12800076
TI  - [Growth of sporadic vestibular schwannomas correlates with Ki-67 proliferation
      index].
AB  - BACKGROUND: Sporadic vestibular schwannoma show a wide variability of their
      growth rate. Some tumors might remain quiescent for a long time without symptoms
      and other tumors might suddenly enlarge. Sometimes during surgical removal of
      tumors, it is useful to have a parameter for the prediction of the further growth
      potential of the schwannoma, especially if tumor resection results in functional
      impairment of the facial nerve. An often used histological parameter for growth
      rate of tumor cells is the proliferation index. METHODS AND PATIENTS: In our
      study we observed a series of 50 patients with neurinoma of the vestibular nerve
      by "wait and scan". After the first magnetic resonance imaging (MRI) all patients
      were controlled by a second MRI. The time between the MRIs ranged between 3 and
      26 months (median 9). In 45 of 50 patients a surgical removal of the tumor by
      transtemporal approach followed. RESULTS: The proliferation index (Ki-67) was
      identified in the histological tumor specimens. The next step was the correlation
      of proliferation index and "tumor doubling time" (TDT). The volume of the tumors
      was provided by measuring three diameters of the tumors in MRI and calculating
      the volume with a formula. The volume of the tumors were used to calculate tumor
      growth and TDT. 10 patients showed no tumor growth during follow up. The average
      TDT in 40 cases was 22 months (SD 16). In 33 cases we were able to determine a
      proliferation index, which showed an average score of 1.99 %. Statistical
      analysis showed a correlation between proliferation index and TDT with a
      coefficient of - 0.42 (s: 0.014). In two cases with relevant clinical tumor
      growth (TDT: 12 months), the MIB-1 index was nearly 0 % in different areas of the
      tumor specimen. May be in these cases, the cell proliferation declined just
      before operation. On the other hand we found one patient with a high
      proliferation index of 3.3 % and a rather long TDT of 19 months. CONCLUSIONS: The
      determination of proliferation can serve as a further decision guidance during
      surgery of vestibular schwannoma.

PMID- 12800075
TI  - [Testing of the macula induced vestibuloocular reflex--possibilities and problems
      in the clinical routine].
AB  - INTRODUCTION: During the last years, an increasing number of papers is presented
      dealing with diseases and diagnostic procedures of the macula function. On the
      other hand, there are just a few distinct test setups for this purpose. In
      clinical routine, this kind of test system has to be efficient and effective to
      diagnostic and therapeutic findings. METHODS: The presented test setup includes
      examination of the semicircular canals by means of harmonic acceleration pendular
      rotation test and the bilateral, bithermal test as well as otolith function tests
      i. e. off vertical axis rotation (OVAR) and eccentric rotation. From March 1999
      to May 2000 522 patients with dizziness were examined. RESULTS: Otolith tests
      results could be assessed in a range between 87 % to 95 % of the cases. The
      quality failure rate was significantly higher than in findings of semicircular
      canals examination procedures. The major caused technical problem were artifacts.
      Looking for the diagnostic relevance of the method, 37 % of the patients.
      Suffering from dizziness and who have normal findings in cupula VOR testing
      procedures revealed isolated macular dysfunctions. DISCUSSION: The relevance for
      diagnostic is demonstrated. Otolith function tests can be applied in clinical
      routine and give relevant information for diagnosis and treatment. Macula test
      procedures are still sophisticated. Technical development of VOG-recording is
      necessary for their general application in otology.

PMID- 12800077
TI  - [Pediatric cost-benefit analysis].
AB  - BACKGROUND: The aim of this study was to explore the cost-benefit-ratio of
      pediatric cochlear implantation for congenitally deaf and prelingually deafened
      children compared to children with hearing aids. The payers' perspective was
      chosen as this is the most relevant for cost discussions. The study should verify
      the hypothesis that educational and associated full costs increase with the age
      at implantation and that these can be below costs for children with hearing aids.
      METHODS: Children implanted at different ages (group 1: 0 - 1.9 yr., group 2: 2 -
      3.9 yr., group 3: 4 - 6.9 yr.) were compared with deaf children using hearing
      aids (group 4). Payers were sick funds and public authorities, the first paying
      for medical and indirect costs, the latter paying for education. Educational
      settings were used as measure for benefit. All costs related to the hearing
      deficiency were included up to the age of 16 years (end of primary education)
      based on 1999 costs. RESULTS: Discounted medical and indirect costs for a
      pediatric cochlear implant user varied between DM 112,000 (53,300 US dollars) and
      DM 91,000 (43,300 US dollars) depending on the age at implantation. Costs for a
      hearing aid user added up to DM 36,000 (17,100 US dollars). These costs were paid
      by the sick funds. Costs for education varied between DM 159,000 (75,700 US
      dollars) for group 1 and DM 257,000 (122,400 US dollars) for group 3 compared to
      DM 277,000 (131,900 US dollars) for hearing aid users. These differences are
      mainly based on the use of mainstream schools. Total costs for sick funds and
      public authorities ad up to DM 271,000 (129,000 US dollars), DM 334,000 (159,000
      US dollars) and DM 348,000 (165,700 US dollars), respectively, for the three age
      groups of implanted children compared to DM 313,000 (148,600 US dollars) for
      hearing aid users. CONCLUSION: This study supports the view that pediatric
      cochlear implantation provides positive cost-benefit ratios compared to hearing
      aid users depending on the age at implantation. From a societal/payer perspective
      implantation of prelingually deafened children is especially recommended for
      children under the age of 2 years. Implantation between ages 2 and 3,9 can be
      recommended from an educational perspective. Implantation at ages >7 years must
      be based on individual decisions considering psychosocial environment, speech and
      language status and type of communication.

PMID- 12800078
TI  - [Incidence and detection of fungi and eosinophilic granulocytes in chronic
      rhinosinusitis].
AB  - BACKGROUND: Chronic Rhinosinusitis (CRS) is the most common chronic disease in
      the United States. Though for Europe no data are available, we have to assume
      that the situation is similar. Although the disease is defined very well by
      clinical symptoms, up to date the etiology and pathogenesis of chronic
      rhinosinusitis are unknown. CRS is considered to be multifactorial, with
      thickening of the mucosa and formation of polyps as an end stage of the disease.
      Treatment of choice includes corticosteroids and/or endoscopic or microscopic
      surgery. Antibiotics only help, if there is an acute bacterial exacerbation of
      the disease. They are not able to cure chronic rhinosinusitis per se. In 1999
      Mayo Clinic researchers published data concerning the incidence of so-called
      "allergic" fungal sinusitis (AFS) in their patients suffering from chronic
      rhinosinusitis, demonstrating the majority of patients investigated presenting
      those criteria. Our own initial data from 2000 confirmed their findings. MATERIAL
      AND METHODS: In an open prospective study fungal cultures were obtained from
      nasal mucus of 238 consecutive patients suffering from CRS. As control group
      acted 23 members of our staff, who did not show any evidence for CRS. In
      addition, in 37 CRS patients surgical specimens (mucus and tissue) were
      investigated histologically for evidence of eosinophilic granulocytes and fungal
      elements. RESULTS: Using new techniques for fungal detection in culture and
      histology as proposed by Mayo Clinic researchers, positive detection of fungal
      cultures of the mucus of our CRS patients developed from 7 % in the past up to 87
      % at present. 91.3 % of our control group yielded a positive result in fungal
      culture. Histologically, eosinophilic clusters were evident in 94.6 % and fungal
      elements were detected in 75.5 % within the mucus of 37 surgical CRS patients.
      Overall, 89.2 % of our surgical patients thus fulfilled the criteria of so-called
      AFS. Compared to our findings in the past, our latest results show an increase of
      80 % in detection of fungal elements in our CRS patients. In all we were able to
      identify 654 positive fungal cultures in 238 CRS patients and 23 healthy controls
      respectively. 88 different genera grew, with 2.4 different species per patient
      and 3.1 different species per healthy control, on average. CONCLUSION: Utilizing
      new techniques of fungal culturing out of the mucus of CRS patients and healthy
      controls, the number of positive fungal cultures increased dramatically from 7 %
      to 87 % in our patients and 91.3 % in healthy controls respectively. To obtain
      these results it is crucial to perform special techniques of mucus sampling and
      pretreatment for culturing as well as for histological investigations. Our
      results show, that with suitable techniques fungi can be identified in almost
      everybody's nose, CRS patient or healthy. When inhaled, those airborne fungi are
      only "in transit" through the nose. Positive fungal cultures from nasal secretion
      therefore have to be considered normal findings. The reason for this delayed
      recognition has to be attributed to our inadequate methods in the past. In
      contrast to healthy controls, clusters of eosinophils and fungal elements are
      present simultaneously within the mucus of CRS patients and appear to be a marker
      of the disease.

PMID- 12800079
TI  - [Extended outcome assessment in endonasal sinus surgery].
AB  - BACKGROUND: Endonasal optically guided surgery has gained wide acceptance for
      treatment of chronic sinusitis. However, irrespective to the advent of minimally
      invasive techniques, standard outcome assessment has not always reflected the
      increased technical and conceptual efforts. "Psychometric" instruments offer
      additional information on patients' perceptions of health. We analyzed the
      practical value of an extended outcome assessment. METHODS: Standardized
      interviews were carried out with 103 patients pre- and postoperatively applying
      several psychometrical instruments ("SF-36" and other valid general health-status
      instruments besides disease-specific questionnaires, providing 124
      items/questions altogether). RESULTS: The diverse changes of subtle health status
      subscores as a rule paralleled each other and were concordant with traditional
      self-estimated global ratings of the surgical success by the patient. Significant
      postoperative changes of the "SF-36" questionnaire were especially seen in the
      subscale "bodily pain" and "level of energy". With few exceptions only, items
      reflecting any indirect burden of chronic sinusitis revealed less pronounced
      improvements postoperatively. CONCLUSION: It appears legitimate to question the
      special benefits of extended psychometric outcome research in comparison to
      traditional global ratings for daily surgical practice.

PMID- 12800080
TI  - [Impact of 24-hour intraesophageal pH monitoring with 2 channels in the diagnosis
      of reflux-induced otolaryngologic disorders].
AB  - BACKGROUND: Patients with gastroesophageal reflux disease (GERD) may suffer from
      a large variety of symptoms in the upper aerodigestive tract such as globus
      sensation, chronic cough, hoarseness and many others. Diagnosis and causal
      therapy may sometimes be difficult with gastroenterologic evaluation sometimes
      revealing no pathologic result. The objective of this study was to determine the
      impact of 24-hour intraesophageal pH monitoring with 2 channels (gastric and
      laryngeal) in the diagnosis of reflux-induced otolaryngologic disorders. METHODS:
      This study included 22 patients presenting to the Department of Otolaryngology
      with symptoms like chronic cough (n = 3), globus sensation and dysphagia (n =
      11), heartburn (n = 2), hoarseness and dysphonia (n = 2) or burning sensation of
      the tongue (n = 1). Three patients had a pathologic formation in the glottic area
      (leukoplakia, granuloma, polyp). All patients underwent a otolaryngological
      examination, a gastroenterological investigation and a 24-hour intraesophageal pH
      monitoring with 2 channels. RESULTS: All 22 patients showed laryngeal mucosal
      lesions (posterior laryngitis). The gastroenterological evaluation with
      esophagogastroduodenoscopy was normal in 4 cases. 13 patients showed a hiatal
      hernia, 4 patients were suffering from a reflux-esophagitis grade I and 2
      patients from grade II. One patient had an erythema and 5 patients showed
      erosions of the gastric mucosa. Seven patients had more than one of the above
      mentioned diagnoses. Intraesophageal pH-monitoring with 2 channels over 24 hours
      revealed a gastroesophageal reflux of all 22 patients and a high reflux to the
      laryngeal level of 21 patients, probably causing laryngopharyngeal symptoms.
      Therapy of the patients consisted of medical antireflux treatment with proton
      pump inhibitor esomeprazol (Nexium, 40 mg, 1-0-0). Within 4 weeks 15 of 22
      patients had no more laryngopharyngeal symptoms or at least a significant
      reduction. CONCLUSION: Patients with laryngopharyngeal symptoms such as
      hoarseness, globus sensation or dysphagia can suffer from GERD, even if typical
      symptoms such as heartburn or retrosternal pain do not exist and gastroesophageal
      intervention reveals a normal result. The best diagnostic instrument for the
      diagnosis of reflux-induced otolaryngologic disorders is a 24-hour
      intraesophageal pH-monitoring with 2 channels (measure-points at the distal
      esophagus and laryngeal level). Medical antireflux treatment should consist of
      proton pump inhibitors (e. g. Nexium) in a dose of 40 mg per day over at least 4
      weeks.

PMID- 12800081
TI  - [Expression of members of the cadherin-/catenin-protein family in juvenile
      angiofibromas].
AB  - BACKGROUND: Angiofibromas are benign, but locally aggressive tumors occurring
      nearly exclusively in adolescent males. Pathogenesis of this fibrovascular
      neoplasm is still unknown. Detection of beta-catenin gene mutations and
      immunohistochemical localization of beta-catenin only in the nuclei of stromal
      cells has been proposed as evidence for the stromal cells to be the neoplastic
      cells in angiofibromas (Abraham et al., 2001). METHODS: Paraffin embedded tissue
      of 13 angiofibromas was analysed immunohistochemically for expression of E
      cadherin, N-cadherin, alpha-catenin, beta-catenin and gamma-catenin. RESULTS: In
      all angiofibromas stromal cells showed in their cytoplasm and their nuclei strong
      immunoreaction for beta-catenin. In 10 out of 13 angiofibromas strong
      immunoreaction was also observed in endothelial cells covering the irregular
      lined vascular spaces. While gamma-catenin was detected in 7 out of 13
      angiofibromas in the stromal cells and endothelial cells, N-cadherin was found
      only in the stromal cells in 8 out of 13 angiofibromas. No significant
      immunoreaction in angiofibromas was seen for E-cadherin and alpha-catenin.
      CONCLUSIONS: Proof of strong beta-catenin-expression in stromal cells and
      endothelial cells stress possible importance of the APC/beta-catenin-pathway in
      angiofibromas, but gives no certain evidence for the assumption that stromal
      cells may be the neoplastic cells. As beta-catenin can increase sensitivity of
      the androgen receptor, it may be assumed that the increased beta-catenin
      expression in angiofibromas is involved in the typical growth stimulus of this
      tumor in adolescent males.

PMID- 12800082
TI  - [Therapy of iatrogenic pharyngocutaneous fistulas--possibilities of surgical
      treatment].
AB  - BACKGROUND: During tumor surgery of the upper respiratory and digestive tract,
      pharyngocutaneuos fistulas may occur postoperatively. Predisposing factors are
      tissue disorders, as can be seen after radiation therapy or wound infections. The
      aim of this study was to create a systematic approach to the treatment of such
      complications. METHODS: Patient charts of oncologic patients with postoperative
      salivary fistulas were analysed retrospectively. According to the surgical
      technique used for treating these fistulas, a systematic strategy for the
      therapeutic management of this complication has been created. RESULTS: Out of 212
      operatively treated tumor patients with pharyngeal reconstruction, 23 developed
      pharyngocutaneous fistulas. A significant higher incidence could be observed in
      patients with wound healing disorders or after radiotherapy. The recurrence rate
      of salivary fistulas has shown to be comparably high when only single layer
      muscular flaps were used. The lowest rate of recurrence could be observed after
      pharyngeal reconstruction using myocutaneous flaps. In only 7 % of our cases, a
      microvascular anastomosis was possible, due to the vascular status. In 85 % of
      our cases, additional fasciocutaneous flaps had to be integrated for complete
      wound closure. This became necessary mainly because of necrosis and dehiscence.
      In 3 cases of severe wound healing disorders with recurrent fistulas, additional
      therapeutic options such as hyperbaric oxygen therapy lead to complete remission.
      CONCLUSION: For the definitive treatment of postoperative salivary fistulas,
      especially in patients with wound healing disorders, a concept of therapeutic
      options using myocutaneous flaps in combination with fasciocutaneous flaps,
      depending on the location, is necessary.

PMID- 12800083
TI  - [Atypical course of cervical vessels--2 case reports].
AB  - BACKGROUND: The atypical course of cervical arteries can be reason for vascular
      complications including stroke and persistent neurological deficits in surgery in
      the cervical region. METHODS: Computed tomography and magnetic resonance imaging
      including angiographic procedures such as contrast enhanced magnetic resonance
      angiography are suitable to detect atypical course of cervical arteries. RESULTS:
      The two cases demonstrate rare variants of atypical course of cervical arteries
      detected by computed tomography and magnetic resonance imaging including contrast
      enhanced magnetic resonance angiography. The knowledge of these variants is
      important for planning of surgical intervention. CONCLUSIONS: Modern imaging
      techniques such as computed tomography and magnetic resonance imaging including
      contrast enhanced magnetic resonance angiography should be used for detection of
      suspected variants in the course of cervical arteries. The relevant structures
      and the abnormalities can be clearly defined.

PMID- 12800084
TI  - [Infusion via venous indwelling catheter in tinnitus treatment].

PMID- 12800085
TI  - [Identification of patients with obstructive sleep apnoea by analysing the muscle
      activity of the floor of the mouth and the sympathetic activity in men during
      wakefulness].

PMID- 12800086
TI  - [Electro-mechanic steering device for head-lamp mounted miniature video cameras].
AB  - BACKGROUND: Endoscopic or microscopic video recordings set a widely established
      standard for medico-legal documentation of operative procedures. In addition,
      they are an essential part of undergraduate as well as postgraduate medical
      education. Macroscopic operations in the head and neck can be recorded by
      miniaturised video cameras attached to the surgeon's head lamp. METHODS: The
      authors present an electro-mechanic steering device which has been designed to
      overcome the parallax error created with a head-mounted video camera, especially
      as the distance of the camera to the operative field varies. RESULTS: The device
      can be operated by the theatre staff, while the sterility of the operative field
      is maintained and the surgeon's physical working range remains unrestricted. As
      the video image is reliably centred to the operative field throughout the
      procedure, a better orientation and understanding for spectators who are
      unfamiliar with the surgical steps is obtained. CONCLUSIONS: While other adverse
      factors to macroscopic head-mounted video recordings, such as involuntary head
      movements of the surgeon, remain unchanged, the device adds to a higher quality
      of video documentation as it relieves the surgeon from adjusting the image field
      to the regions of interest. Additional benefit could be derived from an auto
      focus feature or from image stabilising devices.

PMID- 12800087
TI  - Ovariectomy leads to increased insulin resistance in human apolipoprotein B
      transgenic mice lacking brown adipose tissue.
AB  - We studied the role of estrogen in the gender differences in insulin resistance
      observed in the apoB/BATless mouse, a model of obesity, insulin resistance, and
      hyperlipidemia. Ovariectomized apoB/BATless mice were more obese and more insulin
      resistant than sham ovariectomized apoB/BATless mice. Estrogen replacement by
      subcutaneous pellet reversed the obesity, lowered plasma insulin levels, and
      normalized both glucose tolerance and insulin sensitivity associated with
      ovariectomy. The apoB/BATless mouse should be a good model to delineate the
      molecular mechanisms whereby estrogen protects against insulin resistance.

PMID- 12800088
TI  - Exogenous nitric oxide increases basal leg glucose uptake in humans.
AB  - This study addressed the role of blood flow and nitric oxide in leg glucose
      uptake. Seven subjects (5 men, 2 women) were studied during conditions of resting
      blood flow and increased blood flow, achieved by infusion of the nitric oxide
      (NO) donor sodium nitroprusside (SNP) into the femoral artery. Femoral arterial
      and venous blood samples were obtained and blood flow was determined by infusion
      of indocyanine green dye. SNP infusion significantly increased leg blood flow
      (769 +/- 103 v 450 +/- 65 mL. min(-1). leg(-1), P <.001), but did not affect
      arterial (4.68 +/- 0.13 mmol/L control, 4.63 +/- 0.09 mmol/L SNP) or venous (4.60
      +/- 0.14 mmol/L control, 4.54 +/- 0.10 mmol/L SNP) glucose concentrations.
      Glucose uptake was significantly (P <.01) higher during SNP infusion (65 +/- 6
      micromol. min(-1). leg(-1)) than during the basal period (34 +/- 6 micromol. min(
      1). leg(-1)), whereas lactate release was unaffected (rest, 45 +/- 11 micromol.
      min(-1). leg(-1); SNP, 42 +/- 14 micromol. min(-1). leg(-1)). We conclude that
      blood flow and/or NO increase basal leg glucose uptake.

PMID- 12800089
TI  - Vanadate and rapamycin synergistically enhance insulin-stimulated glucose uptake.
AB  - Tyrosine dephosphorylation, serine phosphorylation, and proteasomal degradation
      of insulin receptor substrates (IRSs) are implicated in the negative regulation
      of insulin action. Here we show that simultaneous inhibition of IRS-1 tyrosine
      dephosphorylation and proteasomal degradation synergistically augments insulin
      responsive glucose uptake. L6 skeletal muscle cells (L6 cells) were treated with
      inhibitors of protein-tyrosine phosphatases, proteasomal degradation, and
      mammalian target of rapamycin (mTOR), and the effects of insulin on glucose
      uptake, IRS-1 tyrosine phosphorylation, phosphatidylinositol (PI) 3-kinase
      activity, and IRS-1 mass were examined. Pretreatment of L6 cells with sodium
      orthovanadate (Na(3)VO(4)) plus the mTOR inhibitor rapamycin caused a 5-fold
      increase in insulin-responsive glucose uptake at 2 hours when compared to insulin
      alone. Evaluation of IRS-1 associated PI 3-kinase activity, IRS-1-associated p85
      mass, and IRS-1 tyrosine phosphorylation showed that 2 hours after insulin
      addition they were reduced by 70% from maximal activity. Likewise, IRS-1 mass was
      reduced by 50%. When L6 cells were pretreated with Na(3)VO(4) plus the proteasome
      inhibitor MG-132 or the mTOR inhibitor rapamycin prior to insulin addition, IRS-1
      mass loss as well as IRS-1/PI-3 kinase complex decay was blocked at 2 hours and
      PI 3-kinase activity was increased 2.5-fold and 4-fold, respectively, over
      insulin alone. Finally, treatment of L6 cells with subtherapeutic amounts of
      vanadyl sulfate and rapamycin induced a synergistic 3-fold increase in insulin
      induced glucose uptake at 2 hours. These findings indicate that vanadium and
      rapamycin synergize to enhance glucose uptake by preventing IRS-1 mass loss and
      IRS-1/PI 3-kinase complex decay and may offer a new approach to enhance glucose
      transport in diabetes.

PMID- 12800090
TI  - Increased vascular endothelial growth factor mRNA expression in the heart of
      streptozotocin-induced diabetic rats.
AB  - The aim of the present study was to evaluate vascular endothelial growth factor
      (VEGF), fms-like tyrosine kinase 1 (flt-1), and fetal liver kinase (flk-1)
      expression in the heart of experimental diabetic rats. Ten young adult male
      Wistar rats (5 streptozotocin [STZ]-induced diabetic rats, without insulin
      treatment, and 5 controls) were studied. Ninety days after the induction of
      diabetes, semiquantitative reverse transcription (RT)-polymerase chain reaction
      (PCR) coamplification of VEGF/glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      transcription was performed. RT-PCR was also performed for VEGF receptors flk-1
      and flt-1. VEGF mRNA expression, at 234 bp, was detectable in the heart of the
      rats and was significantly higher in those with diabetes. Densitometric analysis
      of PCR products showed that VEGF mRNA levels were meanly 4.8-fold higher in STZ
      induced diabetic rats than controls (VEGF/GAPDH densitometric ratio, 3.46 +/-
      0.20 v 0.74 +/- 0.10, P <.001). No significant difference was found in flt-1 and
      flk-1 amplification products between STZ-induced diabetic rats and controls (flt
      1/GAPDH densitometric ratio, 0.58 +/- 0.01 v 0.64 +/- 0.05, P>.1; flk-1/GAPDH
      densitometric ratio, 0.66 +/- 0.10 v 0.7 +/- 0.06, P >.2). The increase in VEGF
      mRNA expression observed in this experimental diabetic model is in contrast with
      the typical impairment in collateral vessels of diabetic hearts. This apparent
      discrepancy might be explained by a resistance of cardiac tissue to VEGF. The
      lack of mRNA flt-1 and flk-1 overexpression in diabetic hearts could be one of
      the mechanisms for this resistance.

PMID- 12800091
TI  - Degradation, cyclic adenosine monophosphate production, insulin secretion, and
      glycemic effects of two novel N-terminal Ala2-substituted analogs of glucose
      dependent insulinotropic polypeptide with preserved biological activity in vivo.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) has significant potential in
      diabetes therapy due to its ability to serve as a glucose-dependent activator of
      insulin secretion. However, its biological activity is severely compromised by
      the ubiquitous enzyme dipeptidylpeptidase IV (DPP IV), which removes the N
      terminal Tyr(1)-Ala(2) dipeptide from GIP. Therefore, 2 novel N-terminal Ala(2)
      substituted analogs of GIP, with Ala substituted by 2-aminobutyric acid (Abu) or
      sarcosine (Sar), were synthesized and tested for metabolic stability and
      biological activity both in vitro and in vivo. Incubation with DPP IV gave half
      lives for degradation of native GIP, (Abu(2))GIP, and (Sar(2))GIP to be 2.3, 1.9,
      and 1.6 hours, respectively, while in human plasma, the half-lives were 6.2, 7.6,
      and 5.4 hours, respectively. In Chinese hamster lung (CHL) cells expressing the
      cloned human GIP receptor, native GIP, (Abu(2))GIP, and (Sar(2))GIP dose
      dependently stimulated cyclic adenosine monophosphate (camp) production with
      EC(50) values of 18.2, 38.5, and 54.6 nmol/L, respectively. In BRIN-BD11 cells,
      both (Abu(2))GIP and (Sar(2))GIP (10(-13) to 10(-8) mol/L) dose-dependently
      stimulated insulin secretion with significantly enhanced effects at 16.7 mmol/L
      compared with 5.6 mmol/L glucose. In obese diabetic (ob/ob) mice, GIP and
      (Sar(2))GIP significantly increased (1.4-fold to 1.5-fold; P <.05) plasma insulin
      concentrations, whereas (Abu(2))GIP exerted only minor effects. Changes in plasma
      glucose were small reflecting the severe insulin resistance of this mutant. The
      present data show that substitution of the penultimate N-terminal Ala(2) in GIP
      by Abu or Sar results in analogs with moderately reduced metabolic stability and
      biological activity in vitro, but with preserved biological activity in vivo.

PMID- 12800092
TI  - Plasma amine oxidase: a postulated cardiovascular risk factor in nondiabetic
      obese patients.
AB  - Increased activity of semicarbazide-sensitive plasma amine oxidase (SSAO), an
      enzyme converting various amines, has been implicated in the generation of
      endothelial damage through formation of cytotoxic reaction products. We
      investigated if SSAO activity is elevated in morbidly obese patients, which might
      contribute to the increased cardiovascular risk associated with obesity. SSAO
      activity was determined in 74 nondiabetic, obese patients (median body mass index
      [BMI]: 42.9 kg/m(2)) and in 32 healthy, non-obese controls (median BMI: 23.3
      kg/m(2)) using a radiometric assay based on the conversion of [(14)C]benzylamine.
      SSAO and parameters of glucose and lipid metabolism were compared for subgroups
      of obese patients with normal (n = 49) and impaired (n = 25) glucose tolerance
      using nonparametric statistical tests. Median SSAO activity was 434 microU/mL in
      obese patients, which was significantly higher than in healthy, non-obese
      controls (median SSAO activity: 361 microU/mL). Median SSAO activity in patients
      with normal and impaired glucose tolerance was 423 and 464 microU/mL,
      respectively. SSAO activity was not correlated with any other clinical or
      laboratory parameters characteristic of the metabolic alterations associated with
      obesity. Elevated SSAO activity is found in nondiabetic, morbidly obese patients
      and might be an interesting independent risk factor for obesity-related
      cardiovascular morbidity. Long-term follow-up of SSAO and its possible role in
      pathogenic events is warranted since intervention with specific SSAO inhibitors
      is available.

PMID- 12800093
TI  - Intake of trans fatty acids and low-density lipoprotein size in a Costa Rican
      population.
AB  - Intervention studies show that dietary composition altered low-density
      lipoprotein (LDL) particle size, but population studies are scarce, and the
      potential effects of trans fatty acids (FA) on LDL size are unknown. Trans FA
      intake has been associated with a more atherogenic lipid profile and increased
      coronary heart disease (CHD). We examined the association between dietary intake,
      including trans FA and LDL size, in 414 randomly selected subjects living in
      Puriscal, Costa Rica. Dietary intake was assessed by a validated food frequency
      questionnaire (FFQ). Women had larger LDL size (A) compared with men (263 v 261),
      and large LDL particles were correlated with increased intake (% energy) of
      protein (P =.005), animal fat (P =.041), trans FA (P <.0001), and decreased
      intake of carbohydrate (P =.052) in sex-, age-, and total energy intake-adjusted
      models. The correlation between trans FA intake and large LDL was significant in
      multivariate models that included dietary and nondietary factors; a 1% difference
      in trans FA was associated with a 2.44 A increase in LDL size (P =.004). In sum,
      it is possible that the effects of dietary factors, such as intake of trans FA on
      CHD are mediated through their effects on LDL size.

PMID- 12800094
TI  - Nicotinic acid-induced insulin resistance is related to increased circulating
      fatty acids and fat oxidation but not muscle lipid content.
AB  - Insulin resistance is associated with increased circulating lipids and skeletal
      muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin
      sensitivity and provides a model of insulin resistance. We hypothesized that the
      reduction in insulin sensitivity occurs via elevation of circulating
      nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid
      (IMCL). A total of 15 nondiabetic males (mean age 27.4 +/- 1.6 years) were
      treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin
      sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by
      euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect
      calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl
      CoA (LCACoA) and triglyceride (TG) content and by (1)H-magnetic resonance
      spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P =.03) and
      nonoxidative glucose disposal (P <.01) and increased fasting NEFAs (P =.01). The
      decrease in GIR related significantly to the increase in fasting NEFAs (r(2)
      =.30, P =.03). The intrasubject increase in basal and clamp fat oxidation
      correlated with the decrease in GIR (r(2) =.45, P <.01 and r(2) =.63, P <.01).
      There were no significant changes in muscle LCACoA, TG, or IMCL content.
      Therefore, induction of insulin resistance by NA occurs with increased
      availability of circulating fatty acids to muscle rather than with increased
      muscle lipid content.

PMID- 12800095
TI  - Protein-tyrosine phosphatase activity in human adipocytes is strongly correlated
      with insulin-stimulated glucose uptake and is a target of insulin-induced
      oxidative inhibition.
AB  - Protein-tyrosine phosphatases (PTPases), in particular PTP1B, have been shown to
      modulate insulin signal transduction in liver and skeletal muscle in animal
      models; however, their role in human adipose tissue remains unclear. The uptake
      of (14)C-D-glucose in response to 10 or 100 nmol/L insulin was measured in
      isolated subcutaneous adipocytes from subjects with a mean age of 44 years
      (range, 26 to 58) and mean body mass index (BMI) of 35.6 (range, 29.7 to 45.5).
      The endogenous activity of total PTPases and specifically of PTP1B in
      immunoprecipitates was measured in cell lysates under an inert atmosphere with
      and without added reducing agents. Using nonlinear regression analysis, higher
      BMI was significantly correlated with lower adipocyte glucose uptake (r = 0.73, P
      =.01) and with increased endogenous total PTPase activity (r = 0.64, P =.04).
      Correlation with waist circumference gave similar results. The endogenous total
      PTPase activity also strongly correlated with insulin-stimulated glucose uptake
      (R =.89, P <.0001); however, the activity of PTP1B was unrelated to the level of
      glucose uptake. Consistent with the insulin-stimulated oxidative inhibition of
      thiol-dependent PTPases reported for 3T3-L1 adipocytes and hepatoma cells,
      treatment of human adipocytes with 100 nmol/L insulin for 5 minutes lowered
      endogenous PTPase activity to 37% of control (P <.001), which was increased 25%
      by subsequent treatment with dithiothreitol in vitro. Cellular treatment with
      diphenyleneiodonium (DPI), an NADPH oxidase inhibitor that blocks the cellular
      generation of H(2)O(2) and reduces the insulin-induced reduction of cellular
      PTPase activity, also diminished insulin-stimulated glucose uptake by 82% (P
      =.001). These data suggest that total cellular PTPase activity, but not the
      activity of PTP1B, is higher in more obese subjects and is negatively associated
      with insulin-stimulated glucose transport. The insulin-stimulated oxidative
      inhibition of PTPases may also have an important permissive role in the
      transmission of the insulin signal to glucose transport in human adipocytes.

PMID- 12800096
TI  - Relative impact of insulin resistance and obesity on cardiovascular risk factors
      in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) affects 5% to 7% of women of reproductive age.
      Insulin resistance and obesity are components of this important syndrome that may
      contribute to excess cardiovascular risk. We analyzed data from 69 patients with
      PCOS who had undergone quantitative assessment of insulin sensitivity, blood
      pressure, lipid profiles, and androgen levels to determine the impact of insulin
      resistance and obesity on parameters of cardiovascular risk. Homeostasis model
      assessment (HOMA) was used to stratify patients in terms of insulin resistance.
      To obtain a reference population, we used data from the National Health and
      Nutrition Examination Study (NHANES III, 1988 to 1994). The most insulin
      resistant tertile of patients exhibited higher body mass index (BMI), androgen
      levels, systolic and diastolic blood pressure (DBP), triglyceride (TG) levels,
      and decreased high-density lipoprotein cholesterol (HDL-C) levels. Insulin
      resistance, not BMI, was the main determinant of HDL-C and TG levels and systolic
      blood pressure (SBP) in PCOS. Among normal women, both BMI and insulin resistance
      influenced cardiovascular risk factors. Insulin resistance was a more significant
      predictor of TGs in women with PCOS than in normal women (P =.008). In contrast
      to normal women, insulin resistance in PCOS appears to be the prime determinant
      of abnormal lipids, blood pressure, and androgens. Thus, early detection of
      insulin resistance, as well as weight reduction, should be emphasized for all
      patients with PCOS.

PMID- 12800097
TI  - Serum homocysteine levels are increased in women with gestational diabetes
      mellitus.
AB  - Serum homocysteine (sHcy) has been found to be elevated in patients with type 2
      diabetes mellitus, as well as in other clinical conditions associated with
      insulin resistance and/or vascular diseases. The aims of this study were to
      measure the relationship between sHcy with biohumoral markers of insulin
      resistance in pregnant women affected with gestational diabetes mellitus (GDM).
      We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral
      glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n =
      15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and
      lipids. In both groups, peripheral insulin sensitivity was measured by using the
      OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was
      significantly higher in the group with GDM compared with nondiabetic women (5.88
      +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related
      to serum folate (r = -.48; P =.0001), and was significantly related to serum
      albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to
      serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and
      serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein
      (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was
      correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood
      pressure (r = -.24; P =.02). GDM remained significantly associated with higher
      sHcy concentrations also after adjusting for age, serum folate, albumin, uric
      acid, ISI(OGTT), and vitamin B(12) (P =.006). In conclusion, we found that sHcy
      is significantly increased in women with GDM, independently of other confounding
      variables, is significantly related to 2-hour OGTT plasma glucose, and seems
      unrelated to insulin resistance in these subjects.

PMID- 12800098
TI  - Relationship between sex hormone-binding globulin levels and features of the
      metabolic syndrome.
AB  - Previous studies have demonstrated that reduced plasma levels of sex hormone
      binding globulin (SHBG) are related to alterations in several features of the
      metabolic syndrome in both men and women. We investigated whether SHBG level was
      a global predictor of the metabolic syndrome in a sample of 203 men, 173
      premenopausal, and 46 postmenopausal women for whom we also obtained a detailed
      assessment of the metabolic profile, including body composition (hydrostatic
      weighing), abdominal adipose tissue areas (computed tomography), plasma lipid
      lipoprotein levels, and glucose homeostasis (oral glucose challenge). Low SHBG
      levels were associated with increased total and abdominal adiposity in men as
      well as in pre- and postmenopausal women. Low SHBG levels were also associated
      with an altered metabolic profile, especially in premenopausal women. Subjects
      were subdivided according to the presence of 0, 1 to 2, or 3 or more features of
      the metabolic syndrome. Twenty-five percent of men were characterized by 3
      features or more, whereas most premenopausal women (61.3%) had a healthy
      metabolic profile (0 features) and 6.9% were characterized by 3 or more features.
      Most postmenopausal women (54.3%) were characterized by 1 to 2 components of the
      metabolic syndrome, and 13.0% were characterized by 3 or more components. The
      proportion of subjects characterized by the metabolic syndrome (3 components or
      more) was lower in subjects with SHBG values in the upper tertile compared with
      the lower tertile in both men and premenopausal women (17.7% v 28.4% and 1.7% v
      14.0%, respectively). Logistic regression analyses indicated that an SHBG level
      in the upper tertile was associated with a significant reduction in the
      probability of being characterized by the metabolic syndrome (odds ratios of
      0.35, P =.02 for men and.11, P =.05 for premenopausal women, with the lower
      tertile as a reference). The logistic regression was not significant in
      postmenopausal women. These results suggest that plasma SHBG level may represent
      a significant predictor of the metabolic syndrome in men and premenopausal women.

PMID- 12800099
TI  - The effect of rosiglitazone on serum lipoprotein(a) levels in Korean patients
      with type 2 diabetes mellitus.
AB  - The aim of the study was to determine if rosiglitazone increases serum levels of
      lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total
      of 118 patients were divided into 2 groups: those with rosiglitazone
      (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n =
      69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous
      treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group
      continued previous treatment with some dose modification for glycemic control.
      The patients had their blood glucose, lipid levels, as well as Lp(a) levels
      assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting
      blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased
      significantly in both groups as compared with the baseline. The fasting glucose
      and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol
      levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to
      212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group
      (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did
      not change in either group. Significant increases in high-density lipoprotein
      (HDL) cholesterol levels were observed in the rosiglitazone group as compared
      with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low
      density lipoprotein (LDL) cholesterol levels increased significantly in the
      rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they
      did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P
      =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone
      group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P
      =.015), approximately a 15% increase in average values. In contrast, there was no
      change in Lp(a) levels in the control group. There was no correlation between the
      changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all
      study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL
      cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus.
      Considering that patients with type 2 diabetes mellitus have increased risks for
      cardiovascular disease, caution should be taken when prescribing rosiglitazone to
      patients who already have other risk factors, such as hypertension and smoking.

PMID- 12800101
TI  - Relationship between gluconeogenesis and glutathione redox state in rabbit kidney
      cortex tubules.
AB  - The intracellular glutathione redox state and the rate of glucose formation were
      studied in rabbit kidney-cortex tubules. In the presence of substrates
      effectively utilized for glucose formation, ie, aspartate + glycerol + octanoate,
      alanine + glycerol + octanoate, malate, or pyruvate, the intracellular reduced
      glutathione/oxidized glutathione (GSH/GSSG) ratios were significantly higher than
      those under conditions of negligible glucose production. Changes in the
      intracellular GSH/GSSG ratio corresponded to those in glucose-6-phosphate content
      and reduced nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide
      adenine dinucleotide phosphate (NADPH/NADP(+)) ratio obtained from
      malate/pyruvate measurements. Gluconeogenesis stimulation by extracellular
      adenosine triphosphate (ATP) or inosine caused an elevation of the intracellular
      GSH/GSSG and NADPH/NADP(+) ratios, as well as glucose-6-phosphate level.
      Surprisingly, in the presence of 5 mmol/L glucose, both the intracellular
      GSH/GSSG and NADPH/NADP(+) ratios and glucose-6-phosphate content were almost as
      low as under conditions of negligible glucose synthesis. L-buthionine sulfoximine
      (BSO)-induced decline in both the intracellular glutathione level and redox state
      resulted in inhibition of gluconeogenesis accompanied by accumulation of
      phosphotrioses and a decrease in fructose-1,6-bisphosphate content, while
      cysteine precursors altered neither GSH redox state nor the rate of glucose
      formation. In view of the data, it seems likely that: (1) intensive
      gluconeogenesis rather than extracellular glucose is responsible for maintaining
      a high intracellular GSH/GSSG ratio due to effective glucose-6-phosphate delivery
      for NADPH generation via the pentose phosphate pathway; (2) a decline in the
      intracellular glutathione level and/or redox state causes a decrease in glucose
      synthesis resulting from a diminished flux through aldolase; (3) induced by
      cysteine precursors, elevation of the intracellular GSH level does not affect the
      rate of glucose formation, probably due to no changes in the intracellular
      GSH/GSSG ratio.

PMID- 12800100
TI  - Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and
      white American women.
AB  - The purpose of this study was to determine if there were differences in the
      capacity of skeletal muscle from morbidly obese Black and White American women to
      oxidize fatty acids. The oxidation rates of (14)C-palmitate, (14)C-palmitoyl-CoA,
      and (14)C-palmitoyl-carnitine were measured in whole homogenates of rectus
      abdominus from Black and White women who were similar in age and body mass index
      (BMI). The activities of muscle citrate synthase (CS), beta-hydroxy acyl-CoA
      dehydrogenase (beta-HAD), and mitochondrial and microsomal acyl-CoA synthetase
      (ACS) were measured in the 2 groups. The results showed that the rate of (14)C
      palmitate oxidation by muscle of Black women was 25% that of Whites (8.7 +/- 1.5
      v 34.4 +/- 6.8 nmol (14)CO(2) produced/gram tissue wet weight/ hour; P <.05), but
      the rates of (14)C-palmitoyl-CoA and (14)C-palmitoyl-carnitine oxidation were not
      different in the 2 groups. No differences were found in the activities of CS or
      beta-HAD. However, the activities of both mitochondrial and microsomal ACS were
      lower in the Black women than the Whites (mitochondrial ACS 25.1 +/- 3.9 v 36.4
      +/- 5.0 nmol/mg protein/min; P <.05; microsomal ACS 6.2 +/- 0.5 v 8.5 +/- 0.5;
      nmol/mg protein/min; P <.005). The lower rate of palmitate oxidation, and the
      lack of differences in the rates of palmitoyl-CoA and palmitoyl-carnitine
      oxidation indicate that there is a defect in the activation of the fatty acid in
      the muscle of the Black women. This was confirmed by the decrease in
      mitochondrial ACS activity in the Black women. The decreased fatty acid oxidation
      by skeletal muscle of obese Black women could result in shunting these fuels from
      muscle to adipose tissue for storage, which may contribute to the maintenance of
      obesity in the Black women.

PMID- 12800102
TI  - Fat oxidation rates are higher during running compared with cycling over a wide
      range of intensities.
AB  - The aim of the present study was to compare the intensity that elicits maximal
      fat oxidation (Fat(max)) determined using a cycle-ergometer and a treadmill-based
      protocol. Twelve moderately trained male subjects (66.9 +/- 1.8 mL. kg(-1). min(
      1)) performed 2 graded exercise tests to exhaustion. One test was performed on a
      cycle ergometer while 1 test was performed on a motorized treadmill; stage
      duration during both trials was 3 minutes. Gas exchange measurements and heart
      rate (HR) recordings were performed throughout exercise. Fat oxidation rates were
      calculated using stoichiometric equations. Maximal fat oxidation rates were
      significantly higher during running compared with cycling (0.65 +/- 0.05 v 0.47
      +/- 0.05 g. min(-1)). However, the intensity, which elicited maximal fat
      oxidation, was not significantly different between the cycle ergometer and
      treadmill test (62.1 +/- 3.1 v 59.2 +/- 2.8% Vo(2)max, respectively). Fat
      oxidation rates were significantly higher during the treadmill test compared with
      the cycle ergometer test from 55 to 80%Vo(2)max. Maximal oxygen uptake and
      maximal HR were significantly higher during the treadmill test. It was concluded
      that fat oxidation rates were higher during walking compared with cycling.
      Maximal fat oxidation was 28% higher when walking compared with cycling, but the
      intensity, which elicits maximal fat oxidation, is not different between these 2
      exercise modes.

PMID- 12800103
TI  - Effect of thiazolidinediones on glucose and fatty acid metabolism in patients
      with type 2 diabetes.
AB  - The current study aimed to compare the effects of treatment (2 months) with
      thiazolidinediones (TZDs) and placebo on glucose and fat metabolism in patients
      with type 2 diabetes (T2DM) in a crossover design. Eight patients received
      placebo (2 months) followed by TZD (2 months). Two-stage (1.5 and 6.0 pmol/kg
      min) hyperinsulinemic-euglycemic clamps were performed in all 8 patients pre- and
      post-placebo and post-TZD (post-placebo = pre-TZD). We determined rates of
      glucose disappearance (G(Rd)), glycolysis (GLS), glycogen synthesis (GS) (all
      with 3-(3)H glucose), carbohydrate (CHO) oxidation (indirect calorimetry),
      endogenous glucose production (EGP), free fatty acid (FFA) release ((2)H(5)
      glycerol), and oxidation (indirect calorimetry) and re-esterification, as well as
      plasma adiponectin and leptin concentrations, and fat cell size and number
      (determined in upper thigh biopsy samples). Placebo treatment had no effects on
      any of the measured parameters. TZD treatment improved insulin-stimulated glucose
      uptake (ISGU) from 17.1 to 26.4 micromol/kg min (P <.01) and insulin-stimulated
      GS from 4.8 to 13.4 micromol/kg min (P < 0.03), potentiated insulin-induced
      suppression of lipolysis from 4.3 to 2.3 micromol/kg min (P <.03) and FFA re
      esterification from 1.9 to 1.0 micromol/kg min (P <.02), increased plasma
      adiponectin levels from 2.7 to 7.2 microg/mL (P <.05), and decreased plasma
      leptin levels from 30.8 to 23.4 ng/mL (P <.02). In addition, TZD tended to
      increase the number of small adipocytes (<50 microm) in subcutaneous adipose
      tissue. We conclude that TZDs have multiple actions and that many, but perhaps
      not all, can be accounted for by their action on adipose tissue.

PMID- 12800104
TI  - Vitamin C metabolomic mapping in experimental diabetes with 6-deoxy-6-fluoro
      ascorbic acid and high resolution 19F-nuclear magnetic resonance spectroscopy.
AB  - Metabolomic mapping is an emerging discipline geared at providing information on
      a large number of metabolites as a complement to genomics and proteomics. Here we
      have probed ascorbic acid homeostasis and degradation in diabetes using 6-deoxy-6
      fluoro ascorbic acid (F-ASA) and 750 MHz (19)F-nuclear magnetic resonance (NMR)
      spectroscopy with proton decoupling In vitro, Cu(2+)-mediated degradation of F
      ASA revealed the formation of 4 major stable degradation products at 24 hours.
      However, when normal or diabetics rats were injected with F-ASA intraperitoneally
      (IP) for 4 days, up to 20 fluorine-labeled compounds were observed in the urine.
      Their composition resembled, in part, metal catalyzed degradation of F-ASA and
      was not explained by spontaneous degradation in the urine. Diabetes led to a
      dramatic increase in urinary F-ASA loss and a relative decrease in most other
      urinary F-compounds. Diabetes tilted F-ASA homeostasis toward oxidation in liver
      (P <.01), kidney (P <.01), spleen (P <.01), and plasma (P <.01), but tended to
      decrease oxidation in brain, adrenal glands, and heart. Surprisingly, however,
      besides the major oxidation product fluoro-dehydroascorbic acid (F-DHA), no F-ASA
      advanced catabolites were detected in tissues at 5 micromol/L sensitivity. These
      findings not only confirm the key role of the kidney in diabetes-mediated loss of
      ascorbic acid, but demonstrate that only selected tissues are prone to increased
      oxidation in diabetes. While the structure of most degradation products needs to
      be established, the method illustrates the power of high resolution (19)F-NMR
      spectroscopy for the mapping of complex metabolomic pathways in disease states.

PMID- 12800105
TI  - Consumption of an oil composed of medium chain triacyglycerols, phytosterols, and
      N-3 fatty acids improves cardiovascular risk profile in overweight women.
AB  - Medium chain triacylglycerols (MCT) have been suggested as efficacious in weight
      management because they possess greater thermogenic qualities relative to long
      chain triacylglycerols; however, MCT may also increase circulating lipid
      concentrations, possibly increasing risk of cardiovascular disease (CVD). The
      present objective was to examine the effect of a diet supplemented with a
      functional oil (FctO) composed of energy expenditure-enhancing MCT (50% of fat),
      cholesterol-lowering phytosterols (22 mg/kg body weight), and triacylglycerol
      suppressing n-3 fatty acids (5% of fat), versus a beef tallow-based diet (BT), on
      plasma lipid and aminothiol concentrations. In a randomized, single-blind,
      crossover design, partially-inpatient trial, 17 overweight women consumed each
      oil as part of a controlled, supervised, targeted energy balance diet for 27
      days, with 4 or 8 weeks of washout between phases. Mean plasma total cholesterol
      concentration was lower (P <.0001), by 9.1%, on FctO (4.37 +/- 0.20 mmol/L)
      versus BT (4.80 +/- 0.20 mmol/L). Mean plasma low-density lipoprotein (LDL)
      cholesterol was also lower (P <.0001) following FctO (2.39 +/- 0.15 mmol/L)
      versus BT (2.86 +/- 0.16 mmol/L), representing a 16.0% difference between diets.
      High-density lipoprotein (HDL) cholesterol and circulating triacylglycerol
      concentrations remained unaffected by treatment. Ratios of HDL:LDL and HDL:total
      cholesterol were higher (P <.01) by 22.0% and 11.0%, respectively, on FctO versus
      BT. Plasma total homocysteine remained unchanged with FctO, but decreased (P
      <.05) with control, hence higher (P <.05) end points were observed with FctO
      (6.95 +/- 0.33 micromol/L) versus BT (6.27 +/- 0.28 micromol/L). Plasma
      glutathione increased (P <.05) by 0.44 micromol/L with FctO supplementation. In
      conclusion, despite equivocal effects on homocysteine levels, consumption of a
      functional oil composed of MCT, phytosterols, and n-3 fatty acids for 27 days
      improves the overall cardiovascular risk profile of overweight women.

PMID- 12800106
TI  - Increased insulin clearance in peroxisome proliferator-activated receptor gamma2
      Pro12Ala.
AB  - The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor
      (PPARgamma(2)) is associated with reduced risk for type 2 diabetes. Although
      increased insulin sensitivity of glucose disposal and lipolysis has been
      reported, the exact mechanism by which the risk reduction is conferred is not
      clear. Because the conclusion of greater insulin sensitivity hinged upon lower
      insulin levels in some studies, it is possible that more efficient insulin
      clearance is involved. We therefore estimated insulin clearance during a
      euglycemic hyperinsulinemic clamp (insulin infusion rate divided by steady-state
      insulin concentration, 229 normal glucose tolerant [NGT] subjects), an oral
      glucose tolerance test (OGTT) (mean C-peptide divided by mean insulin
      concentrations, 406 NGT, 54 impaired glucose tolerant or mildly diabetic
      subjects), and a hyperglycemic clamp (120 minutes, 10 mmol/L, C-peptide divided
      by insulin in the steady-state, 56 NGT subjects). In the carriers of the Ala
      allele (prevalence approximately 24%), insulin clearance in all 3 protocols was
      significantly greater ( approximately 10%), than in controls. While the results
      from the euglycemic clamp reflect both hepatic and peripheral insulin clearance,
      those from the OGTT and the hyperglycemic clamp reflect mainly hepatic insulin
      extraction. Free fatty acids (FFA) during the steady state of the euglycemic
      hyperinsulinemic clamp were significantly lower in carriers of the Ala allele (26
      +/- 5 micromol/L) than in controls (46 +/- 3 micromol/L, P =.02). In conclusion,
      the Pro12Ala polymorphism is associated with increased insulin clearance. This
      could be the result of reduced FFA delivery, which has been shown to improve
      hepatic insulin removal and sensitivity. Because PPARgamma(2) is mainly expressed
      in adipose tissue, one of the main regulatory effects of the polymorphism may
      well be the more efficient suppression of (possibly intra-abdominal) lipolysis.

PMID- 12800107
TI  - Relationships in men of sex hormones, insulin, adiposity, and risk factors for
      myocardial infarction.
AB  - That sex hormones, insulin, and obesity all correlate with the constellation of
      risk factors for myocardial infarction (MI) that has come to be known as
      "syndrome X," the "insulin-resistance syndrome," or the "metabolic syndrome"
      suggests that any one or more of them could underlie and link the risk factors to
      form the constellation. That sex hormones, insulin, and obesity also correlate
      with each other complicates their identification as an underlying link. To
      compare the likelihood of each being a link, we measured and determined the
      interrelationships of sex hormones, insulin, adiposity variables, and risk
      factors for MI in 80 apparently healthy men. Of the adiposity variables, visceral
      adipose tissue (VAT) correlated more strongly with the risk factors for MI than
      did body mass index (BMI), total adipose tissue (TAT), subcutaneous adipose
      tissue (SCAT), waist-to-hip ratio (WHR), and waist circumference (W). Controlling
      for VAT eliminated all of the other adiposity correlations that had been
      significant. VAT, therefore, was used as the measure of adiposity for further
      data analysis. VAT correlated more strongly with risk factors for MI than did sex
      hormones and insulin, and most of the correlations of sex hormones and insulin
      with risk factors for MI lost statistical significance after controlling for VAT.
      Testosterone and the ratio of estradiol-to-testosterone (E/T) correlated with
      insulin; on controlling for VAT, only the E/T-insulin correlation remained
      significant (r =.38, P <.001) and on multiple linear regression analysis, insulin
      was associated with estradiol (P =.01) and testosterone (P =.04) independently of
      VAT and age. In conclusion, (1) VAT in men may largely explain the correlations
      of sex hormones, insulin, and obesity with the risk factors for MI measured, (2)
      VAT may be the principal factor in men, independently of other measures of
      adiposity, that links risk factors for MI to form the constellation, and (3)
      estradiol may play a more important role in the sex hormone-insulin relationship
      in men than has generally been considered.

PMID- 12800108
TI  - Prevention of ischemic heart failure by exercise in spontaneously diabetic BB Wor
      rats subjected to insulin withdrawal.
AB  - Poor metabolic control resulting from insulin withdrawal in chronic type 1
      diabetic rats results in ischemic heart failure. In the present study, we
      determined whether heart failure occurs in acute type 1 diabetic rats following
      insulin withdrawal and if prior exercise training can prevent this dysfunction.
      Four-week-old diabetic prone BB Wor rats were either sedentary or moderately
      exercised by daily treadmill running. Training was discontinued at the onset of
      diabetes. Isolated working rat heart function was then assessed in the following
      groups: diabetic resistant, uncontrolled sedentary diabetic (USD), controlled
      sedentary diabetic (CSD), uncontrolled trained diabetic (UTD), and controlled
      trained diabetic (CTD) rats. To induce an uncontrolled state, insulin treatment
      was withheld for 24 hours. During increased metabolic demand and reperfusion
      following ischemia, heart rate, contractility, and cardiac output were depressed
      in hearts from USD animals. Treatment with insulin prevented the depressions in
      cardiac performance from occurring. Hearts from UTD rats perfused under these
      conditions showed comparable cardiac function to that seen in the controlled
      state. This occurred despite poor metabolic control, reflected by elevated levels
      of plasma glucose and free fatty acids. Our results indicate that metabolic
      deteriorations in acute diabetes result in ischemic heart failure. However, this
      cardiac dysfunction can be prevented with exercise training.

PMID- 12800109
TI  - No influence of the PPARgamma2 Pro12Ala genotype on serum adiponectin
      concentrations in healthy Europeans.

PMID- 12800116
TI  - Improving communication in the ICU using daily goals.
AB  - BACKGROUND: Clear communication is imperative if teams in any industry expect to
      make improvements. An estimated 85% of errors across industries result from
      communication failures. PURPOSE: The purpose of this study was to evaluate and
      improve the effectiveness of communication during patient care rounds in the
      intensive care unit (ICU) using a daily goals form. DESIGN: We conducted a
      prospective cohort study in collaboration with the Volunteer Hospital Association
      (VHA), Institute for Healthcare Improvement (IHI), and Johns Hopkins Hospital's
      (JHH) 16-bed surgical oncology ICU. All patients admitted to the ICU were
      eligible. Main outcome variables were ICU length of stay (LOS) and percent of ICU
      residents and nurses who understood the goals of care for patients in the ICU.
      Baseline measurements were compared with measurements of understanding after
      implementation of a daily goals form. RESULTS: At baseline, less than 10% of
      residents and nurses understood the goals of care for the day. After implementing
      the daily goals form, greater than 95% of nurses and residents understood the
      goals of care for the day. After implementation of the daily goals form, ICU LOS
      decreased from a mean of 2.2 days to 1.1 days. CONCLUSION: Implementing the daily
      goals form resulted in a significant improvement in the percent of residents and
      nurses who understood the goals of care for the day and a reduction in ICU LOS.
      The use of the daily goals form has broad applicability in acute care medicine.

PMID- 12800117
TI  - The use of benchmarking to identify top performing critical care units: a
      preliminary assessment of their policies and practices.
AB  - PURPOSE: To describe the policies and practices of intensive care units (ICUs)
      with good patient survival and highly efficient resource use and to identify
      relevant variables for future investigation. MATERIALS AND METHODS: We used
      clinical data for 359,715 patients from 108 ICUs to compare the ratios of actual
      with Acute Physiology and Chronic Health Evaluation (APACHE) III predicted
      hospital mortality, ICU and hospital stay, and the proportion of low-risk monitor
      patients. The best performing ICUs (top 10%) were defined by a mortality ratio of
      1.0 or less, and either the lowest ratio for ICU stay, hospital stay, or
      percentage of low-risk monitor patients. The medical and nursing directors of top
      performing ICUs completed a questionnaire to describe their unit's structure
      policies and practices. RESULTS: Among the 108 ICUs, 61 (56%) had a ratio of
      actual to predicted hospital mortality of 1.0 or less and the best performing
      units had ICU stay ratios of 0.62 to 0.79, hospital stay ratios of 0.73 to 0.77,
      and admitted 10% to 38% low-risk monitor patients. ICU structure varied among the
      best performing ICUs. Units with the shortest ICU and hospital stay had
      alternatives to intensive care, methods to facilitate patient throughput, used
      multiple protocols for high-volume diagnoses and care processes, and continuously
      monitored resource use. Units with the fewest low-risk monitor patients screened
      potential admissions, had intermediate care areas, extended-stay recovery rooms,
      and care pathways for high-volume diagnoses. CONCLUSIONS: Benchmarking can be
      used to identify ICUs with good patient survival and highly efficient resource
      use. The combination of policies and practices used by these units might improve
      resource use in other ICUs.

PMID- 12800118
TI  - Improving the utilization of medical crisis teams (Condition C) at an urban
      tertiary care hospital.
AB  - PURPOSE: Serious clinical deterioration precedes most cardiopulmonary arrests,
      and there is evidence that organized responses to this deterioration may prevent
      a substantial proportion of in-hospital deaths. We aimed to increase the
      utilization of our medical crisis response team (Condition C) to impact this
      source of mortality. METHODS: We have examined the change in numbers of Condition
      Cs and the main alternative response strategy (sequential stat pages) after the
      implementation of 4 strategies to increase Condition C utilization: (1) immediate
      reviews of all sequential STAT pages, (2) feedback to caregivers responsible for
      delays in Condition C activation, (3) creation of objective criteria for invoking
      a crisis response, and (4) dissemination of objective criteria through posting in
      units, e-mail, and in-service oral presentations. RESULTS: Over a 3-year period,
      interventions were followed by increased use of organized responses to medical
      crises (Condition Cs) and decreased numbers of disorganized responses (sequential
      STAT pages). The interventions that involved objective definition and
      dissemination of criteria for initiating the Condition C response were followed
      by 19.2 more Condition Cs monthly (95% confidence interval [CI], 12.1-26.3;
      P<0001) and 5.7 fewer sequential STAT pages monthly (95% CI, 3.2-8.2). The
      interventions that involved giving feedback to medical personnel based on review
      of their care were not associated with changes in the measures. CONCLUSION:
      Utilization of an important patient safety measure may be increased by focused
      interventions at an urban tertiary care hospital.

PMID- 12800119
TI  - The ICU outreach team.

PMID- 12800120
TI  - A study of once-daily amikacin with low peak target concentrations in intensive
      care unit patients: pharmacokinetics and associated outcomes.
AB  - PURPOSE: The aim of this study was to assess the pharmacokinetics of
      individualized amikacin single-dosage regimens targeting low peak serum
      concentrations in a population of intensive care unit (ICU) patients, and to
      describe the outcomes associated with this dosing strategy. MATERIALS AND
      METHODS: In this prospective, noncomparative, pharmacokinetic study, 36 ICU
      patients with adequate renal function were treated with amikacin (intravenous
      infusion), in combination with other antibiotics, for hospital-acquired
      infections. The initial doses of amikacin were calculated based on individual
      creatinine clearance values whereas subsequent doses were calculated by using the
      amikacin pharmacokinetic parameters estimated from the serum concentration-time
      data of each individual patient (samples were drawn postinfusion, 1 h, 3 h, 6 h,
      and 10 h after the onset of the infusion and just before the next dose on days 2,
      4, and 7 of therapy). RESULTS: Results showed moderate only interpatient and lack
      of intrapatient (except for the volume of distribution) variability in amikacin
      pharmacokinetic parameters. There were no significant differences between
      achieved and target peak levels. Clinical response was noted in 94% and
      bacteriologic response was noted in 86% of patients. Nephrotoxicity did not occur
      during or after treatment. CONCLUSIONS: Amikacin dosage individualization with
      low peak target concentrations was successful for the 36 ICU patients. This
      dosing strategy was not associated with nephrotoxicity, but conclusions on
      clinical efficacy cannot be drawn from this limited study.

PMID- 12800121
TI  - Commentary: once-daily aminoglycoside dosing: where are we now?

PMID- 12800122
TI  - Circulating endotoxin and antiendotoxin antibodies during severe sepsis and
      septic shock.
AB  - The presence of circulating endotoxin is common during sepsis but its prognostic
      value is poor. We hypothesized that this lack of correlation with outcome could
      be related in part to the presence of circulating antiendotoxin antibodies. In a
      14-bed medical intensive care unit, in an 821-bed tertiary teaching hospital, we
      prospectively assessed endotoxin and antiendotoxin antibodies in patients with
      severe sepsis or septic shock. Blood samples for the determination of circulating
      endotoxin and antiendotoxin antibodies were drawn when severe sepsis or septic
      shock were diagnosed (day 0) and then on day 1, day 2, and day 4. Daily
      measurements of antiendotoxin antibodies did not discriminate survivors from
      nonsurvivors. No antibody depletion was observed. However, during follow-up, the
      antiendotoxin immunoglobulin (Ig)M antibody level increased among survivors but
      decreased among nonsurvivors (51.2 vs -44.8 MU/mL, P=007). Circulating endotoxin
      was detectable among 9 of 17 patients on inclusion but neither the basal value
      nor sequential measurements correlated with outcome. These results suggest that
      during severe sepsis and septic shock, circulating endotoxin is a poor prognostic
      marker whereas the detection of an increase in IgM antiendotoxin antibody levels
      could identify survivors. This increase in IgM antibody levels could be
      attributed to a reactivation of the immune system.

PMID- 12800123
TI  - A novel regional citrate anticoagulation protocol for CRRT using only
      commercially available solutions.
AB  - PURPOSE: To describe a citrate regional anticoagulation (CRA) protocol for
      patients with acute renal failure and contraindications to heparin who require
      continuous renal replacement therapy (CRRT), using only commercially available
      solutions, for units that do not want or cannot prepare extemporaneously made
      solutions. MATERIALS AND METHODS: Case report and series from a medical/surgical
      intensive care unit of a university teaching hospital. A CRA protocol was
      developed by using only commercially available solutions. Five dialysis-specific
      clinical parameters were identified to allow simplified measurement and control.
      RESULTS: There was a dramatic improvement of dialysis filter survival in the
      index patient that was seen in the subsequent patients receiving CRA. This was
      accompanied by excellent control of the clinical and biochemical parameters as
      well as nursing acceptance and ownership of the protocol. CONCLUSION: It is
      possible to provide safe and effective CRA with only commercially available
      solutions. The protocol is applicable to most patients requiring CRRT.

PMID- 12800124
TI  - Estimates of attributable mortality of systemic candida infection in the ICU.

PMID- 12800126
TI  - Safety issues in pharmacotherapy for smoking in patients with cardiovascular
      disease.
AB  - Twenty percent of patients with cardiovascular disease smoke, and smoking
      cessation results in a dramatic decline in the relative risk of future
      cardiovascular events. Questions regarding the safety of nicotine-replacement
      therapy and bupropion SR for smoking cessation in patients with cardiovascular
      disease have arisen, in particular because of potential hemodynamic effects of
      these agents. There have been several randomized, controlled, clinical trials
      testing the safety of transdermal nicotine in patients with cardiovascular
      disease that failed to show an increased risk for cardiac events in active
      treatment conditions compared with placebo. Efficacy trials conducted in other
      patient populations also support the safety of nicotine-replacement use in
      cardiac disease patients. To date there is one randomized controlled trial to
      test bupropion for smoking cessation conducted in this population. Studies to
      test the efficacy of bupropion for smoking cessation and depression suggest it is
      safe to use in cardiac disease patients despite recent case reports of adverse
      events associated with bupropion use. Nicotine-replacement therapy and bupropion
      significantly increase long-term smoking cessation rates, and the benefits of
      cessation exceed the risks for pharmacotherapy in patients with cardiovascular
      disease.

PMID- 12800127
TI  - Smoking and endothelial function.
AB  - The arterial endothelium is a vital homeostatic cell layer responsible for a
      variety of functions such as thromboresistance, control of vessel tone, and
      vessel growth. Recent evidence has indicated that both active and passive
      cigarette smoking are associated with dysfunction of normal endothelial
      physiology, in a dose dependent and potentially reversible way. Endothelial
      abnormalities may predispose to the atherogenic and thrombotic problems
      associated with cigarette smoking.

PMID- 12800128
TI  - Hospital- and clinic-based smoking cessation interventions for smokers with
      cardiovascular disease.
AB  - Cigarette smoking is the leading preventable cause of death in the United States
      and a major risk factor for cardiovascular disease (CVD). Large observational
      epidemiologic studies conducted in diverse populations have demonstrated a strong
      association between smoking and CVD morbidity and mortality. Observational
      epidemiologic studies have also demonstrated a substantial benefit of smoking
      cessation on cardiovascular morbidity and mortality. Smoking cessation after
      myocardial infarction reduces subsequent cardiovascular mortality by nearly 50%.
      Therefore, the use of effective strategies to reduce the prevalence of tobacco
      use is a high priority for both the primary and secondary prevention of CVD.
      Effective smoking cessation interventions have been identified in randomized
      controlled trials in the general population of smokers. These methods, which
      include behavioral counseling and pharmacotherapy, are incorporated into clinical
      practice guidelines for physicians in the United States and Great Britain. A
      smaller but still substantial body of evidence demonstrates the efficacy of these
      interventions in hospital- and clinic-based settings for smokers with CVD. This
      evidence is sufficient to support the routine implementation of these smoking
      cessation methods in inpatient and outpatient settings for smokers with CVD.

PMID- 12800129
TI  - Reperfusion in acute myocardial infarction: current concepts.
AB  - Myocardial reperfusion is the treatment of choice in acute myocardial infarction.
      Pharmacological thrombolysis restores coronary artery patency in about two thirds
      of patients with acute myocardial infarction. However, mechanical reperfusion
      with primary angioplasty and stenting achieves higher patency rates with less
      complications, especially in high-risk patients. Adjunctive pharmacotherapy and
      new device technology may improve the outcome of primary angioplasty. Facilitated
      angioplasty using a combination of half-dose thrombolysis, platelet glycoprotein
      IIb/IIIa antagonists, and early intervention, appears to be a promising strategy
      for the treatment of acute myocardial infarction in the modern era. The efficacy
      and safety of this approach are currently evaluated in several ongoing trials.

PMID- 12800130
TI  - Contrast agent--associated nephrotoxicity.
AB  - Radiocontrast media can lead to a reversible form of acute renal failure that
      begins soon after the contrast dye administration and generally is benign.
      Contrast media accounts for 10% of all causes of hospital-acquired acute renal
      failure and represents the third leading cause of in-hospital renal function
      deterioration after decreased renal perfusion and postoperative renal
      insufficiency. The in-hospital mortality rate in patients developing renal
      insufficiency is related directly to the magnitude increase of serum creatinine
      concentration. The mortality rate ranges from 3.8% with an increase in serum
      creatinine level of 0.5 to 0.9 mg/dL to 64% with an increase of greater than 3.0
      mg/dL. The mechanism by which contrast-induced renal failure occurs is not well
      understood. Contrast agent-associated nephrotoxicity appears to be a result of
      direct contrast-induced renal tubular epithelial cell toxicity and renal
      medullary ischemia. Furthermore, a key mechanism seems to be alteration in renal
      dynamics, probably caused by imbalances between vasodilator and vasoconstrictor
      factors, including the activities of nitric oxide, prostaglandins, endothelin,
      and reactive oxygen species. The optimal strategy to prevent contrast-associated
      nephrotoxicity remains uncertain. At present, recommendations are as follows: (1)
      periprocedural hydration, (2) use of a low-osmolality contrast, and (3) limiting
      the amount of contrast agent. Recently, considerable interest has resulted from
      the preliminary positive data on the effectiveness of prophylactic administration
      of acetylcysteine and fenoldopam. The former may prevent the direct oxidative
      tissue damage, whereas the latter is a selective intrarenal vasodilator.

PMID- 12800131
TI  - Enzymatic catalysis via liquid-liquid interfaces.
AB  - Enzymes acting in a biphasic liquid of water and organic solvent may show
      catalytic activity dependent on the amount of phase interface available. Such an
      effect may be caused by several mechanisms. For example, for hydroxynitrile lyase
      from Prunus amygdalus, substrate mass transfer limitation has been advocated, but
      also adsorption of the enzyme on the interface. In this commentary it is shown
      that often these two mechanisms will have qualitatively similar consequences. The
      reaction rate will be influenced by the organic substrate concentration, by the
      initial enzyme concentration, and by the volume-specific interfacial area, and
      these influences will be linear at low values but reach a saturation level at
      high values. To rule out any of the models, their quantitative mathematical
      descriptions should be compared, taking into account that both models may be
      valid simultaneously.

PMID- 12800132
TI  - Novel type of in situ extraction: Use of solvent containing microcapsules for the
      bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces
      cerevisiae.
AB  - A novel in situ product removal (ISPR) method that uses microcapsules to extract
      inhibitory products from the reaction suspension is introduced into fermentation
      technology. More specifically, L-phenylalanine (L-Phe) was transformed by
      Saccharomyces cerevisiae to 2-phenylethanol (PEA), which is inhibitory toward the
      yeast. In order to continuously remove PEA from the vicinity of the cells, the
      reaction suspension was brought into contact with capsules of 2.2-mm diameter
      that had a hydrophobic core of dibutyl sebacate and an alginate-based wall. This
      novel process combines the advantages of a normal in situ extraction process
      (fast mass transfer and simple process set-up) with the benefits of a membrane
      based process (reduction of the solvent toxicity and avoidance of stable
      emulsions). In particular, the microbial cells are shielded from the phase
      toxicity of the organic solvent by a hydrogel layer surrounding the organic core.
      By placing the microcapsules into the fermenter, the final overall concentration
      of PEA in a fed-batch culture was increased from 3.8 to 5.6 g/L because a part of
      the inhibitory product dissolved in the dibutyl sebacate core. In another
      fermentation experiment, the capsules were placed in a fluidized bed that was
      connected via a loop to the fermenter. In addition, the fluidized bed was
      connected via a second loop to a back-extractor to regenerate the capsules. By
      alternating the extraction and back-extraction cycles, it was possible to limit
      the PEA concentration of the fed-batch culture in the fermenter to 2.4 g/L while
      producing important quantities of PEA that accumulated in an external reservoir.

PMID- 12800133
TI  - Combined sequence and structure analysis of the fungal laccase family.
AB  - Plant and fungal laccases belong to the family of multi-copper oxidases and show
      much broader substrate specificity than other members of the family. Laccases
      have consequently been of interest for potential industrial applications. We have
      analyzed the essential sequence features of fungal laccases based on multiple
      sequence alignments of more than 100 laccases. This has resulted in
      identification of a set of four ungapped sequence regions, L1-L4, as the overall
      signature sequences that can be used to identify the laccases, distinguishing
      them within the broader class of multi-copper oxidases. The 12 amino acid
      residues in the enzymes serving as the copper ligands are housed within these
      four identified conserved regions, of which L2 and L4 conform to the earlier
      reported copper signature sequences of multi-copper oxidases while L1 and L3 are
      distinctive to the laccases. The mapping of regions L1-L4 on to the three
      dimensional structure of the Coprinus cinerius laccase indicates that many of the
      non-copper-ligating residues of the conserved regions could be critical in
      maintaining a specific, more or less C-2 symmetric, protein conformational motif
      characterizing the active site apparatus of the enzymes. The observed
      intraprotein homologies between L1 and L3 and between L2 and L4 at both the
      structure and the sequence levels suggest that the quasi C-2 symmetric active
      site conformational motif may have arisen from a structural duplication event
      that neither the sequence homology analysis nor the structure homology analysis
      alone would have unraveled. Although the sequence and structure homology is not
      detectable in the rest of the protein, the relative orientation of region L1 with
      L2 is similar to that of L3 with L4. The structure duplication of first-shell and
      second-shell residues has become cryptic because the intraprotein sequence
      homology noticeable for a given laccase becomes significant only after comparing
      the conservation pattern in several fungal laccases. The identified motifs, L1
      L4, can be useful in searching the newly sequenced genomes for putative laccase
      enzymes.

PMID- 12800134
TI  - Critical evaluation of sampling techniques for residual glucose determination in
      carbon-limited chemostat culture of Saccharomyces cerevisiae.
AB  - In this paper, three sampling techniques for rapid quenching of cellular
      metabolism and subsequent separation of cells from fermentation broth are
      compared: (i) quick freezing of fermentation broth directly in liquid nitrogen;
      (ii) quenching metabolism by exposing the fermentation broth to stainless steel
      beads (4-mm diameter) in a filter syringe precooled to -18 degrees C; and (iii)
      withdrawal of the filtrate through a 0.45 microm filter attached to a syringe and
      a needle inserted directly into the fermentor. It was concluded that use of
      liquid nitrogen as a quenching method to rapidly arrest cellular metabolism, for
      quantitative analysis of extracellular glucose, is not a very reliable method and
      that the filter syringe steel beads work very well.

PMID- 12800135
TI  - Profiling of dynamic changes in hypermetabolic livers.
AB  - The liver plays an important role in the overall negative nitrogen balance
      leading to muscle wasting commonly observed in patients following many
      conditions, including severe injury, cancer, and diabetes. In order to study
      changes in liver metabolism during the establishment of such catabolic states, we
      used a rat skin burn injury model that induces hypermetabolism and muscle
      wasting. At various times during the first week following the injury, livers were
      isolated and perfused in a recirculating system under well-defined conditions. We
      applied a steady-state metabolic flux analysis model of liver metabolism and then
      used k-means clustering to objectively group together reaction flux time
      profiles. We identified six distinct groups of reactions that were differentially
      responsive: (1) pentose phosphate pathway (PPP); (2) amino acid oxidation
      reactions leading to the formation of tricarboxylic acid (TCA) cycle
      intermediates; (3) gluconeogenesis; (4) TCA-cycle and mitochondrial oxidation;
      (5) lipolysis, beta-oxidation, and ketone body formation; and (6) urea-cycle.
      Burn injury sequentially upregulated the urea-cycle, the PPP, and the TCA-cycle,
      in order, while beta-oxidation and gluconeogenesis remained unchanged. The
      upregulation of the PPP was transient, whereas the rise in urea- and TCA-cycle
      fluxes was sustained. An ATP balance predicted an increased production of ATP and
      energy expenditure starting on day 3 post-burn, which correlated with the
      induction of the oxidative phosphorylation uncoupler uncoupling protein-2. We
      conclude that metabolic profiling using flux analysis and clustering analysis is
      a useful methodology to characterize the differential activation of metabolic
      pathways in perfused organs and to identify specific key pathways that are
      sensitive to a stimulus or insult without making a priori assumptions.

PMID- 12800136
TI  - Micro-assembly of functionalized particulate monolayer on C18-derivatized SiO2
      surfaces.
AB  - This work describes a simple approach to immobilize functionalized colloidal
      microstructures onto a C(18)-coated SiO(2) substrate via specific or non-specific
      bio-mediated interactions. Biotinylated bovine serum albumin pre-adsorbed onto a
      C(18) surface was used to mediate the surface assembly of streptavidin-coated
      microbeads (2.8 microm), while a bare C(18) surface was used to immobilize anti
      Listeria antibody-coated microbeads (2.8 microm) through hydrophobic
      interactions. For a C(18) surface pre-adsorbed with bovine serum albumin,
      hydrophobic polystyrene microbeads (0.8 microm) and positively charged
      dimethylamino microbeads (0.8 microm) were allowed to self-assemble onto the
      surface. A monolayer with high surface coverage was observed for both polystyrene
      and dimethylamino microbeads. The adsorption characteristics of Escherichia coli
      and Listeria monocytogenes on these microbead-based surfaces were studied using
      fluorescence microscopy. Both streptavidin microbeads pre-adsorbed with
      biotinylated anti-Listeria antibody and anti-Listeria antibody-coated microbeads
      showed specific capture of L. monocytogenes, while polystyrene and dimethylamino
      microbeads captured both E. coli and L. monocytogenes non-specifically. The
      preparation of microbead-based surfaces for the construction of microfluidic
      devices for separation, detection, or analysis of specific biological species is
      discussed.

PMID- 12800137
TI  - Growth dynamics of Artemisia annua hairy roots in three culture systems.
AB  - The transient growth of Artemisia annua hairy roots was compared for cultures
      grown in shake flasks and in bubble column and mist reactors. Instantaneous
      growth rates were obtained by numerically differentiating the transient biomass
      measurements. Specific sugar consumption rates showed good agreement with
      literature values. From the growth rate and sugar consumption rate, the specific
      yield and maintenance coefficient for sugar were determined for all three culture
      systems. These values were statistically indistinguishable for roots grown in
      shake flasks and bubble columns. In contrast, the values for roots grown in
      bubble columns and mist reactors were statistically different, suggesting that
      sugar utilization by roots grown in these two systems may be different. By
      measuring respiration rates in the bubble column reactor we also determined the
      actual biomass yield and maintenance coefficient for O(2) and CO(2). Together
      with an elemental analysis of the roots, this allowed us to obtain a reasonable
      carbon balance.

PMID- 12800138
TI  - Optimal covalent immobilization of glucose oxidase-containing liposomes for
      highly stable biocatalyst in bioreactor.
AB  - The glucose oxidase-containing liposomes (GOL) were prepared by entrapping
      glucose oxidase (GO) in the liposomes composed of phosphatidylcholine (PC),
      dimyristoyl L-alpha-phosphatidylethanolamine (DMPE), and cholesterol (Chol) and
      then covalently immobilized in the glutaraldehyde-activated chitosan gel beads.
      The immobilized GOL gel beads (IGOL) were characterized to obtain a highly stable
      biocatalyst applicable to bioreactor. At first, the glutaraldehyde concentration
      used in the gel beads activation as well as the immobilizing temperature and time
      were optimized to enhance the immobilization yield of the GOL to the highest
      extent. The liposome membrane composition and liposome size were then optimized
      to obtain the greatest possible immobilization yield of the GOL, the highest
      possible activity efficiency of the IGOL, and the lowest possible leakage of the
      entrapped GO during the GOL immobilization. As a result, the optimal
      immobilization conditions were found to be as follows: the liposome composition,
      PC/DMPE/Chol = 65/5/30 (molar percentage); the liposome size, 100 nm; the
      glutaraldehyde concentration, 2% (w/v); the immobilizing temperature, 4 degrees
      C; and the immobilizing time, 10 h. Furthermore, the optimal IGOL prepared were
      characterized by its rapidly increasing effective GO activity to the externally
      added substrate (glucose) with increasing temperature from 20 to 40 degrees C,
      and also by its high stability at 40 degrees C against not only the thermal
      denaturation in a long-term (7 days) incubation but also the bubbling stress in a
      bubble column. Finally, compared to the conventionally immobilized glucose
      oxidase (IGO), the higher operational stability of the optimal IGOL was verified
      by using it either repeatedly (4 times) or for a long time (7 days) to catalyze
      the glucose oxidation in a small-scale airlift bioreactor.

PMID- 12800139
TI  - Scale-down of continuous filtration for rapid bioprocess design: Recovery and
      dewatering of protein precipitate suspensions.
AB  - The early specification of bioprocesses often has to be achieved with small (tens
      of millilitres) quantities of process material. If extensive process discovery is
      to be avoided at pilot or industrial scale, it is necessary that scale-down
      methods be created that not only examine the conditions of process stages but
      also allows production of realistic output streams (i.e., streams truly
      representative of the large scale). These output streams can then be used in the
      development of subsequent purification operations. The traditional approach to
      predicting filtration operations is via a bench-scale pressure filter using
      constant pressure tests to examine the effect of pressure on the filtrate flux
      rate and filter cake dewatering. Interpretation of the results into cake
      resistance at unit applied pressure (alpha) and compressibility (n) is used to
      predict the pressure profile required to maintain the filtrate flux rate at a
      constant predetermined value. This article reports on the operation of a
      continuous mode laboratory filter in such a way as to prepare filter cakes and
      filtrate similar to what may be achieved at the industrial scale. Analysis of the
      filtration rate profile indicated the filter cake to have changing properties
      (compressibility) with time. Using the insight gained from the new scale-down
      methodology gave predictions of the flux profile in a pilot-scale candle filter
      superior to those obtained from the traditional batch filter used for laboratory
      development.

PMID- 12800140
TI  - Effect of heat on phycoerythrin fluorescence: Influence of thermal exposure on
      the fluorescence emission of R-phycoerythrin.
AB  - The goal of this work was to measure and model the effect of thermal exposure on
      the fluorescence emission of R-phycoerythrin (R-PE). The long-term objective of
      our work is to assess the feasibility of encapsulating R-PE for use as the
      critical component of a time-temperature integrator (TTI) for ascertaining the
      degree of inactivation of food pathogens such as Salmonella. In this article we
      present a study to measure and model the thermally induced fluorescence emission
      decay of R-PE in several isothermal experiments. We used the isothermal data to
      determine the kinetic parameters, based on a general n(th) order reaction, and
      evaluated the utility of the resulting model by using it to predict R-PE
      fluorescence emission decay for several nonisothermal experiments based on
      published USDA safe harbor guidelines for cooked beef products. The transient
      experiments were conducted over the same temperature range used in the isothermal
      study. Very good agreement was obtained between theory and experiment at
      temperatures of 62.8 degrees C and above, although the model slightly
      underpredicted the extent of fluorescence emission decay at 60 degrees C. Our
      results indicate that R-PE fluorescence emission decay kinetics is well behaved
      and that the protein is a strong candidate for use as a time-temperature
      integrator.

PMID- 12800141
TI  - Role of water-soluble polysaccharides in bacterial cellulose production.
AB  - Acetobacter xylinum BPR2001 produces water-insoluble bacterial cellulose (BC) and
      a water-soluble polysaccharide called acetan in corn steep liquor-fructose
      medium. Acetobacter xylinum EP1, which is incapable of acetan production was
      derived by disrupting the aceA gene of BPR2001. The BC production by EP1 (2.88
      g/L) was lower than that by BPR2001 (4.6 g/L) in baffled-flask culture. When
      purified acetan or agar was added to the medium from the start of cultivation,
      the BC production by EP1 was enhanced and the final BC yield of EP1 was almost
      the same as that of BPR2001. A similar improvement of BC production by EP1 by the
      addition of agar was also confirmed by cultivation in a 50-L airlift reactor.
      From these results, the role of acetan in BC production is associated with the
      increase in the viscosity of the culture medium which may hinder coagulation of
      BC and cells in the culture, thereby accelerating the growth of BPR2001 and BC
      production by BPR2001.

PMID- 12800142
TI  - Biofiltration of a mixture of volatile organic compounds on granular activated
      carbon.
AB  - The performance of a biofilter packed with Active Carbon (AC) was evaluated. The
      effluent (alcohol, ketones, esters, aromatic and chlorinated compounds) treated
      was a representative mixture of most common industrial emissions. To achieve a
      better knowledge of multicomponent adsorption mechanisms, and to underline the
      interest of inoculating AC, a control abiotic humidified filter had been operated
      in the same conditions as the biofilter. For a load of 110 g VOC m(-3) AC h(-1),
      after 55 days of operation, the removal efficiency was higher in the biotic than
      in the abiotic filter (85% vs 55%, respectively). Moreover, in the biofilter, at
      steady state, the elimination of all compounds was almost complete except for
      chlorinated compounds and p-xylene (removal efficiency of 25% and 64%,
      respectively). The microbial colonization of AC involved a decrease of the
      adsorption sites accessibility and enhanced the treatment of VOCs (volatile
      organic compounds) having a lower affinity for activated carbon. Moreover, while
      aromatic compounds and MIBK were eliminated along the overall height of the
      biofilter, pollutants with reduced affinity for AC, such as methanol, acetone,
      and halogenated compounds were only treated on the second half of the reactor.
      Thus, the affinity for activated carbon was an important parameter controlling
      the biodegradation process. Nevertheless, the use of AC as packing material in
      biofilters treating complex mixtures of VOCs is limited. Actually, similar
      removal efficiency could be reached, in the same conditions, for a biofilter
      packed with granular peat. Furthermore, for the biofilter packed with AC, the
      column height necessary to remove biodegradable compounds, with reduced affinity
      for the support, was important.

PMID- 12800143
TI  - Analyses of microbial desulfurization reaction of alkylated dibenzothiophenes
      dissolved in oil phase.
AB  - The kinetics of the oil/water two-phase reaction system was analyzed, and the
      reaction was carried out with the desulfurization of alkylated dibenzothiophenes
      (Cx-DBTs) using the desulfurizing microorganism Mycobacterium sp. G3. In the
      water-phase reaction system, the desulfurization activities were constant with
      respect to species of Cx-DBTs as substrates. However, the desulfurization
      activities in the oil/water two-phase reaction system against DBT, 4,6-dimethyl
      DBT, 4,6-diethyl DBT, 4,6-dipropyl DBT, and 4,6-dibutyl DBT were 49.0, 45.9,
      11.5, 1.35, and 0.00 micromol g DCW(-1) h(-1), respectively. The kinetic
      parameters for the degradation of DBT, 4,6-dimethyl DBT, and 4,6-diethyl DBT were
      also obtained (V(max) values 90.0, 68.7, and 22.7 micromol g DCW(-1) h(-1) and
      K(m) values 0.21, 0.70, and 3.03 mM, respectively). The reason for the decrease
      in activity against Cx-DBTs of high molecular weight was a decrease in the V(max)
      value and an increase in the K(m) value, the latter being a particularly serious
      problem. Furthermore, the hydrophobicity of the substrate was evaluated as the
      capacity factor measured by high-performance liquid chromatography (HPLC). The
      correlation between substrate hydrophobicity and desulfurization activity
      indicated that the desulfurization reaction in the oil/water two-phase reaction
      system is greatly influenced by the hydrophobicity of the substrates. In
      addition, the influence of the solvent on desulfurization activity was examined,
      and it was found that not only the hydrophobicity of substrates, but also that of
      solvents, affected the desulfurization reaction.

PMID- 12800144
TI  - Interfacial versus homogeneous enzymatic cleavage of mandelonitrile by
      hydroxynitrile lyase in a biphasic system.
AB  - The question of an interfacial versus a homogeneous reaction is carefully
      addressed for the enzymatic biphasic cleavage of mandelonitrile to benzaldehyde
      by Prunus amygdalus hydroxynitrile lyase (pa-Hnl) (Hickel et al. [1999]
      Biotechnol Bioeng 36:425-436). Experimental evidence, including 1) the reaction
      ceases when the interface is populated by previously adsorbed denatured pa-Hnl,
      2) the reaction continues even after washout of the bulk enzyme from the aqueous
      phase, 3) highly nonpolar organic solvents initially promote fast reaction
      kinetics that relatively quickly decay to zero product production, and 4) the
      reaction rate is nonlinear in the bulk enzyme concentration, provide robust
      grounds for an interfacial reaction. We also model enzymatic mandelonitrile
      cleavage assuming a homogeneous aqueous-phase reaction. The homogeneous reaction
      scheme does not simultaneously account for the experimental observations of a
      linear dependence of the reaction rate on organic/water interfacial area, no
      dependence on the aqueous-phase volume, and a nonlinear dependence on pa-Hnl
      aqueous concentration. Further, simple calculations demonstrate that the
      homogeneous reaction rate is at least three orders of magnitude slower than those
      observed by Hickel et al. (1999). We again conclude that enzyme adsorbed at the
      organic solvent/water interface primarily catalyzes the biphasic mandelonitrile
      cleavage reaction.

PMID- 12800145
TI  - A recurrent chromosome translocation breakpoint in breast and pancreatic cancer
      cell lines targets the neuregulin/NRG1 gene.
AB  - The 8p11-21 region is a frequent target of alterations in breast cancer and other
      carcinomas. We surveyed 34 breast tumor cell lines and 9 pancreatic cancer cell
      lines for alterations of this region by use of multicolor fluorescence in situ
      hybridization (M-FISH) and BAC-specific FISH. We describe a recurrent chromosome
      translocation breakpoint that targets the NRG1 gene on 8p12. NRG1 encodes growth
      factors of the neuregulin/heregulin-1 family that are ligands for tyrosine kinase
      receptors of the ERBB family. Breakpoints within the NRG1 gene were found in four
      of the breast tumor cell lines: ZR-75-1, in a dic(8;11); HCC1937, in a
      t(8;10)(p12;p12.1); SUM-52, in an hsr(8)(p12); UACC-812, in a t(3;8); and in two
      of the pancreatic cancer cell lines: PaTu I, in a der(8)t(4;8); and SUIT-2, in a
      del(8)(p). Mapping by two-color FISH showed that the breaks were scattered over
      1.1 Mb within the NRG1 gene. It is already known that the MDA-MB-175 breast tumor
      cell line has a dic(8;11), with a breakpoint in NRG1 that fuses NRG1 to the DOC4
      gene on 11q13. Thus, we have found a total of seven breakpoints, in two types of
      cancer cell lines, that target the NRG1 gene. This suggests that the NRG1 locus
      is a recurring target of translocations in carcinomas. PCR analysis of reverse
      transcribed cell line RNAs revealed an extensive complexity of the NRG1
      transcripts but failed to detect a consistent pattern of mRNA isoforms in the
      cell lines with NRG1 breakpoint.

PMID- 12800146
TI  - Genomic imbalances in CML blast crisis: 8q24.12-q24.13 segment identified as a
      common region of over-representation.
AB  - The acute phase of chronic myeloid leukemia (CML) is accompanied by secondary
      chromosomal changes. The additional changes have a non-random pattern; however,
      highly abnormal (marker) chromosomes are reported in some 20% of abnormal
      karyotypes. These marker chromosomes have proved to be beyond the resolution of
      conventional G-banding analysis. We used molecular cytogenetic techniques to
      determine the structure of complex chromosome markers in 10 CML-derived cell
      lines after our investigations of CML patients in blast crisis. Multicolor
      fluorescence in situ hybridization identified a multitude of structural
      chromosome aberrations. In addition, genomic gains identified by comparative
      genomic hybridization (CGH) were mapped to highly complex marker chromosomes in
      more than one cell line. The most common genomic loss detected by CGH affected
      chromosome 9, whereas the most common genomic gains affected, in order of
      frequency, the sequences of 8q, 6, and 13q. The smallest discrete amplification
      on 8q was identified in cell line MEG-01. This amplicon contains sequences
      represented by the marker D8S263/RMC08P029 but did not contain the proximal MYC
      gene or a more distal marker, D8S256/RMC08P025. We determined the size of the
      amplicon to be less than the chromosome segment 8q24.12-q24.13. The use of region
      and locus-specific probes to analyze the organization of highly complex marker
      structures aided the identification of preferentially amplified genomic regions.
      The resultant amplifications could harbor gene(s) driving disease progression.

PMID- 12800147
TI  - Monochromosome transfer provides functional evidence for growth-suppressive genes
      on chromosome 14 in nasopharyngeal carcinoma.
AB  - In many cancers, including nasopharyngeal carcinoma (NPC), extensive and multiple
      regions of allelic loss occur on chromosome 14. However, to date no functionally
      conclusive tumor suppressor genes have yet been identified on this chromosome.
      Through use of the monochromosome transfer technique, this study provides
      functional evidence for the importance of two discrete regions of chromosome 14.
      A newly established A9 mouse donor cell line containing an intact copy of
      chromosome 14 was used for transfer of this intact chromosome into the NPC HONE1
      cell line. Twelve independently established microcell hybrids demonstrated
      uniform loss of specific chromosome 14 loci from both endogenous and exogenous
      alleles. By microsatellite typing and fluorescence in situ hybridization with BAC
      probes, the two critical regions were localized to 14q11.2-13.1 and 14q32.1.
      Selective elimination of these regions during hybrid selection was strongly
      associated with both hybrid survival and tumor growth in vivo. This functional
      evidence now narrows down the candidate areas for further studies and suggests
      that at least two hitherto unidentified growth-related genes localized on two
      critical regions of chromosome arm 14q play an important role in tumorigenesis.

PMID- 12800148
TI  - Analysis of colorectal tumor progression by microdissection and comparative
      genomic hybridization.
AB  - This investigation aimed to identify patterns of copy number change in colorectal
      tumor progression from adenoma to liver metastasis. Fifty-three microdissected
      sub-regions from 17 cases of colorectal cancer were assigned to one of six
      histopathologically defined categories: coexisting adenoma, tumor above the
      muscularis layer, tumor within the muscularis layer, tumor extending through the
      bowel wall to serosal fat, lymph node metastasis, and liver metastasis.
      Microdissected samples were treated by a microwave processing step and then used
      as templates for universal PCR amplification. PCR products were fluorophore
      labeled and subjected to comparative genomic hybridization. Copy number changes
      were found in all samples, and every chromosome arm (excluding acrocentric short
      arms) was affected. More losses than gains were detected, but there were no
      significant differences between the numbers of changes seen in each category.
      Each individual sample revealed unique changes, additional to those shared within
      each case. The most frequently observed gains were of X and 12q. The most common
      losses were of 8p, 16p, 9p, 15q, 18q, and 10q. Nominally significant associations
      were observed between metastatic tumor and loss of 12q24.1 or 10p13-14, non
      metastatic tumor and loss of 8q24.1, tumor extending to serosal fat and loss of
      6q24-25 or gain of 4q11-13, tumor extending to serosal fat and metastatic lesions
      and loss of 4q32-34 or 22q11-12, and adenoma and loss of 15q24. Loss of 4q32-34
      remained highly significant after correction for multiple testing. Adenoma was
      the only category not to show loss of 17p. These data reveal a genetically
      heterogeneous picture of tumor progression, with a small number of changes
      associated with advanced disease.

PMID- 12800149
TI  - Xq27-28 deletions in prostate carcinoma.
AB  - Linkage studies have implicated a prostate cancer susceptibility locus at Xq27-28
      (termed HPCX), estimated to be responsible for approximately 16% of hereditary
      prostate cancer cases. To date, this region has not been investigated in sporadic
      disease. In this study, we examined tumor DNA samples prepared from patients with
      sporadic prostate cancer, prostate cancer cell lines, and prostate cancer
      xenografts for evidence of genomic alterations within the Xq27-28 region. To
      facilitate the detection of nullizygosity, we examined a unique series of highly
      tumor-enriched DNA samples prepared from men with multi-sampled metastatic
      prostate cancer, as well as a series of prostate cancer xenografts and cell
      lines. PCR amplification of carcinoma and normal DNA templates was performed for
      11 loci spanning an Xq27-28 interval of approximately 16 cM. Among 19 patients
      studied, somatic deletions in this region were found in two cases. Within these
      two cases, each independent metastatic tumor sample available from an individual
      (n = 4 sites and 8 sites, respectively) showed the same reduction to
      nullizygosity, suggesting a pre-metastatic origin for the deletion events in
      both. Mapping of the deletion boundaries with eight additional sets of markers
      indicated that both deletions had breakpoints within an approximately 500- to 800
      kb interval containing FMR1; however, the deletions were non-overlapping. The
      lack of a common region of deletion suggests one of three possibilities: (1) that
      these two deletions are unrelated, (2) that the deletions affect the opposite
      ends of an as yet unknown gene, or (3) that each deletion has inactivated a
      single copy of an unknown gene arranged in cis in the region of interest. These
      data clearly indicate that deletions do occur within the HPCX locus in a subset
      of sporadic prostate cancers and therefore raises the possibility that the gene
      at this locus may prove to play a role in sporadic disease.

PMID- 12800150
TI  - 11q13 alterations in two cases of hibernoma: large heterozygous deletions and
      rearrangement breakpoints near GARP in 11q13.5.
AB  - Hibernomas are rare, benign tumors with a histological appearance resembling that
      of brown adipose tissue. The diagnosis of hibernomas may be difficult because
      some of them contain only a small number of the characteristic multivacuolated
      fat cells and can be mistakenly classified as well-differentiated liposarcomas.
      Cytogenetic information has been reported for 10 cases, showing that these tumors
      are characterized by structural rearrangements involving 11q13. Previous
      fluorescence in situ hybridization (FISH) studies revealed consistent and
      sometimes cryptic losses of the MEN1 region in 11q13.1. Here, we describe the
      molecular cytogenetic analysis of two new hibernoma cases. Both tumors showed
      complex rearrangements, simultaneously including translocations, inversions, and
      deletions affecting the pair of chromosomes 11. The translocation partners were
      chromosome 5 in one case and chromosomes 16 and 22 in the other case. The 11q13
      region was concomitantly rearranged on both chromosomes 11. FISH studies revealed
      large heterozygous deletions within the 11q13 band, from 11q13.1 to 11q13.5.
      Genes such as PYGM, MEN1, CCND1, FGF3, ARIX, and GARP were deleted, showing that
      the size of the 11q13 altered region was larger than previously reported.
      Furthermore, both tumors had breakpoints in 11q13.5, one of them in the immediate
      proximity of the GARP gene. Our results suggest that rearrangements of GARP or a
      neighboring gene may be important for the pathogenesis of hibernomas.

PMID- 12800151
TI  - Molecular characterization of acute leukemias by use of microarray technology.
AB  - Accurate subclassification of leukemia and the identification of prognostic
      determinants are essential to guide therapy and to improve patients' outcome.
      According to present standards, pre-therapeutic assessment depends on a
      combination of different methods. We aimed to expand the molecular
      characterization of different acute leukemia subtypes to identify new genome-wide
      diagnostic markers. Total RNA from 90 adult patients suffering from acute
      lymphoblastic leukemia (ALL, n = 25) and acute myeloid leukemia (AML, n = 65) was
      extracted at diagnosis and high density oligonucleotide microarrays were used to
      analyze the expression profiles of 12,000/22,000 genes in all specimens
      (Affymetrix U95Av2/U133A). All cases were thoroughly characterized by individual
      combinations of cytomorphology, cytogenetics, multiparameter immunophenotyping,
      and molecular genetics. The expression signature of a small set of differentially
      expressed genes was sufficient to accurately discriminate eight clinically
      relevant acute leukemia subgroups. Underlying chromosomal aberrations or
      immunophenotypical characteristics were strictly correlated with a distinct gene
      expression pattern for AML with t(8;21), t(15;17), t(11q23)/MLL, or inv(16) as
      well as for precursor B-ALL with t(9;22), t(8;14), or t(11q23)/MLL and precursor
      T-ALL. These data support a possible future application of microarray technology
      for classification of the acute leukemias.

PMID- 12800152
TI  - Prenatal chromosomal diversification of leukemia in monozygotic twins.
AB  - Previous studies on concordant acute lymphoblastic leukemia (ALL) in identical
      twins have identified the leukemia as monoclonal with MLL or ETV6-RUNX1 gene
      fusion as early or initiating events in utero. In the latter case, postnatal
      latency is associated with secondary genetic events such as ETV6 deletion. We
      describe here a pair of infant twins with concordant acute monoblastic leukemia
      (AML). They are a unique pair in that their leukemia blasts display extensive
      intraclonal chromosomal diversity. Comparison of the leukemic cells between the
      two twins by karyotype and fluorescence in situ hybridization identifies a common
      or shared stem line and extensive subclonal diversity for which the twins'
      leukemic populations are divergent. This case of leukemia illustrates in utero
      initiation with early imposition of chromosomal instability, the progressively
      divergent evolution of which can be mapped in the twins into pre- and postnatal
      periods.

PMID- 12800153
TI  - A new chromosome banding technique, spectral color banding (SCAN), for full
      characterization of chromosomal abnormalities.
AB  - We have developed spectral color banding (SCAN) as a new chromosome banding
      technique based on spectral analysis of differentially labeled chromosome band
      specific painting probes. In this study, we succeeded in displaying a multicolor
      banding pattern for chromosome 3, which was almost identical to the pattern
      obtained with the corresponding G-banding. We applied this method to metaphase
      cells from different normal male donors with various levels of G-banding
      resolution, ranging from 250 to 850 bands per haploid set. The same multicolor
      banding pattern was observed in all samples regardless of the length of the
      chromosomes or the quality of the G-banding. We then used SCAN in a diffuse large
      B-cell lymphoma case for a complete analysis of the intrachromosomal change for
      chromosome 3, which could not be fully characterized by G-banding or even by
      spectral karyotyping (SKY). SCAN could detect the duplicated segment and identify
      the origin of the chromosome band on the basis of the specific spectral color of
      each band. This study demonstrates that SCAN is a useful tool for full
      characterization of chromosomal abnormalities not identified by SKY.

PMID- 12800154
TI  - More extensive genetic alterations in unmutated than in hypermutated cases of
      chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) is not a uniform disease entity;
      approximately half of the CLL cases have undergone immunoglobulin V(H) gene
      hypermutation, whereas the other half display unmutated V(H) genes. We
      investigated genome changes in 12 hypermutated cases (M-CLL) and 22 unmutated
      cases (UM-CLL) by use of comparative genomic hybridization, G-banding, and
      multicolor fluorescence in situ hybridization (m-FISH) after optimal mitogen
      stimulation and FISH analysis of typical CLL aberrations: 11q deletion, 13q
      deletion, and trisomy 12. Very high frequencies of aberrations were found in both
      groups: 82% in UM-CLL and 83% in M-CLL. Deletions of 11q and 13q were equally
      distributed in M-CLL and UM-CLL. However, larger aberrations detectable by CGH,
      trisomy 12, and complex aberrations were less frequent in M-CLL than in UM-CLL.
      These observations led to a hypothesis that unmutated and mutated CLL have
      different biological Backgrounds, given that large and/or complex chromosomal
      aberrations and hypermutation of the CLL progenitor cells tend to be mutually
      exclusive.

PMID- 12800155
TI  - Identification of candidate tumor-suppressor genes in 6q27 by combined deletion
      mapping and electronic expression profiling in lymphoid neoplasms.
AB  - Deletions in the long arm of chromosome 6 (6q) are among the most frequent
      chromosome aberrations in lymphoid neoplasms. Recently, the region of minimal
      deletion (RMD1) in 6q27 was narrowed down to 5-9 Mb. In the present study, we
      aimed to define the distal border of the commonly lost region in 6q27 more
      precisely and to identify and investigate tumor-suppressor genes (TSGs) from this
      region. Twenty-nine cases, in which our previous fluorescence in situ
      hybridization (FISH) screening that used a set of 36 YAC probes revealed loss in
      6q25-27, were further investigated by means of FISH. In all cases, deletions of
      6q27 extended from yeast artificial chromosome (YAC) 977e10 spanning the proximal
      border of RMD1 to the most telomeric YAC 933f7 within the recently established
      YAC-contig of this region. An interstitial homozygous deletion, flanked by the
      telomeric probe TelVysion6q and YAC 971g12, was detected, which substantially
      narrows down the RMD1. To identify candidate TSGs down-regulated in malignant
      lymphomas from this region of homozygous loss, we performed electronic profiling
      of expressed sequences mapped to this region. This analysis suggested the gene
      PDCD2 originally thought to be involved in programmed cell death to be probably
      down-regulated in malignant B-cell lymphomas compared to normal B lymphocytes.
      Nevertheless, mutation analyses failed to identify mutations in the coding region
      of PDCD2 in nine lymphomas with FISH-proved 6q27 deletions. Furthermore,
      epigenetic studies in these nine and an additional 48 lymphomas did not show
      altered methylation of the PDCD2 locus in these tumors. Possibly
      haploinsufficiency is effectual in accelerating tumor progression.

PMID- 12800161
TI  - Molecules with helical structure: how to build a molecular spiral staircase.

PMID- 12800156
TI  - Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic
      large cell lymphoma.
AB  - In anaplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to
      NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations
      result in the expression of chimeric ALK transcripts that are translated into
      fusion proteins with tyrosine kinase activity and oncogenic properties. We report
      a case showing a restricted cytoplasmic staining pattern of ALK and a novel
      chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ
      hybridization analysis. The result of 5' RACE analysis showed that the ALK gene
      was fused in-frame to a portion of the non-muscle myosin heavy chain gene, MYH9.
      Nucleotide sequence of the MYH9-ALK chimeric cDNA revealed that the ALK
      breakpoint was different from all those previously reported. It is localized in
      the same exonic sequence as MSN-ALK, but 6 bp downstream, resulting in an in
      frame fusion of the two partner proteins. In contrast to the previously reported
      ALK fusion proteins, MYH9-ALK may lack a functional oligomerization domain.
      However, biochemical analysis showed that the new fusion protein is tyrosine
      phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If
      further investigations confirm this latter result, the in vivo tyrosine
      phosphorylation of MYH9-ALK protein could involve mechanisms different from those
      described in the other ALK hybrid proteins.

PMID- 12800162
TI  - Reductive electron transfer and transport of excess electrons in DNA.
AB  - In principle, DNA-mediated charge transfer processes can be categorized as either
      oxidative hole transfer or reductive electron transfer. In research on DNA
      damage, major efforts have focused on the investigation of oxidative hole
      transfer or transport, resulting in insights on the mechanisms. On the other
      hand, the transport or transfer of excess electrons has a large potential for
      biomedical applications, mainly for DNA chip technology. Yet the mechanistic
      details of this type of charge transfer chemistry were unclear. In the last two
      years this mechanism has been addressed in gamma-pulse radiolysis studies with
      randomly DNA-bound electron acceptors or traps. The major disadvantage of this
      experimental setup is that the electron injection and trapping is not site
      selective. More recently, new photochemical assays for the chemical and
      spectroscopic investigation of reductive electron transfer and electron migration
      in DNA have been published which give new insights into these processes. Based on
      these results, an electron-hopping mechanism is proposed which involves
      pyrimidine radical anions as intermediate electron carriers.

PMID- 12800163
TI  - Modulation of protein-protein interactions with small organic molecules.
AB  - Many proteins exert their biological roles as components of complexes, and the
      functions of proteins are often determined by their specific interactions with
      other proteins. Because of the central importance of protein-protein interactions
      for cellular processes, the ability to interfere with specific protein-protein
      interactions provides a powerful means of influencing the function of selected
      proteins within the cell. Cell-permeable small organic modulators of protein
      protein interactions are thus highly desirable tools both for the study of
      physiological cellular processes and for the treatment of numerous diseased
      states. Herein a number of protein-protein interactions that are considered to be
      pharmaceutical targets are presented, which will familiarize the reader with the
      strategies that have been employed for the successful identification of small
      molecule modulators of these protein-protein interactions. These encouraging
      examples suggest that combined research efforts in the areas of functional
      proteomics, assay development, and organic synthesis will open up novel
      possibilities for the treatment of human diseases in the future.

PMID- 12800164
TI  - The first ozonide of a phosphorus oxide--preparation, characterization, and
      structure of P4O18.

PMID- 12800166
TI  - Simple two-step ipso substitution of aromatic carboxylic acids by alkyl halides.

PMID- 12800165
TI  - Efficient enantioselective total synthesis of (-)-epipodophyllotoxin.

PMID- 12800167
TI  - A phosphorane as supported acylanion equivalent: linker reagents for smooth and
      versatile C-C coupling reactions.

PMID- 12800168
TI  - A metal-carbene carbohydrate amphiphile as a low-molecular-mass organometallic
      gelator.

PMID- 12800169
TI  - A topology paradigm for metal-organic zeolites.

PMID- 12800170
TI  - Phototriggered drug release from functionalized oligonucleotides by a molecular
      beacon strategy.

PMID- 12800171
TI  - Overcoming degeneracy in carbohydrate recognition.

PMID- 12800172
TI  - A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity
      of an enzyme active site: evidence for C-F...C=O interactions.

PMID- 12800173
TI  - The high-resolution solution structure of epothilone A bound to tubulin: an
      understanding of the structure-activity relationships for a powerful class of
      antitumor agents.

PMID- 12800174
TI  - Derivation of dihedral angles from CH-CH dipolar-dipolar cross-correlated
      relaxation rates: a C-C torsion involving a quaternary carbon atom in epothilone
      A bound to tubulin.

PMID- 12800175
TI  - Synthesis and conformational analysis of (E)-9,10-dehydroepothilone B: a
      suggestive link between the chemistry and biology of epothilones.

PMID- 12800176
TI  - A total synthesis of epothilones using solid-supported reagents and scavengers.

PMID- 12800177
TI  - Enantioselective total synthesis of the cyclotryptamine alkaloid idiospermuline.

PMID- 12800178
TI  - Enantioselective total syntheses of the cyclotryptamine alkaloids hodgkinsine and
      hodgkinsine B.

PMID- 12800179
TI  - Diastereomeric differentiation in the quenching of excited states by hydrogen
      donors.

PMID- 12800180
TI  - Kinetic control in direct alpha-silyloxy ketone synthesis: a new regiospecific
      catalyzed cross silyl benzoin reaction.

PMID- 12800181
TI  - Solid-phase synthesis of sialylglycopeptides through selective esterification of
      the sialic acid residues of an Asn-linked complex-type sialyloligosaccharide.

PMID- 12800182
TI  - Stereospecific construction of contiguous quaternary and tertiary stereocenters
      by rearrangement from indoline-2-methanol to 2,2,3-trisubstituted
      tetrahydroquinoline: application to an efficient total synthesis of natural
      virantmycin.

PMID- 12800183
TI  - Crystal structure of a cyclic enterobacterial common antigen.

PMID- 12800184
TI  - Reductive dimerization of tethered pyrenes: implications for the reduction of
      polcyclic aromatic hydrocarbons.

PMID- 12800185
TI  - Highly diastereoselective tandem reduction-allylation reactions of 1,4-diketones
      with zirconocene-olefin complexes.

PMID- 12800187
TI  - c-Kit is preferentially expressed in MYCN-amplified neuroblastoma and its effect
      on cell proliferation is inhibited in vitro by STI-571.
AB  - Coexpression for c-Kit receptor and its ligand stem cell factor (SCF) has been
      described in neuroblastoma (NB) cell lines and tumors, suggesting the existence
      of an autocrine loop modulating tumor growth. We evaluated c-Kit and SCF
      expression by immunohistochemistry in a series of 75 primary newly diagnosed
      neuroblastic tumors. Immunostaining for c-Kit was found in 10/75 and for SCF in
      17/75, with 5/10 c-Kit-positive tumors also expressing SCF. For both, c-Kit and
      SCF staining were predominantly found in the most aggressive subset of tumors,
      i.e., those amplified for MYCN: c-Kit was detected in 8/14 amplified vs. 2/61
      single copy (p<0.001), and SCF in 9/14 amplified vs. 8/61 single copy tumors
      (p<0.001). Furthermore, the association of c-Kit expression with advanced stage
      (3 or 4) (p=0.001) and of SCF expression with adrenal primary (p=0.03) was
      substantiated. The in vitro activity of the tyrosine kinase inhibitor STI-571
      (imatinib mesylate, Gleevec, Glivec) on NB cell lines positive or negative for c
      Kit was also assessed. When cells were grown in 10% fetal calf serum, the 4 c-Kit
      positive cell lines tested were sensitive to STI-571 growth inhibition to a
      different extent (ranging from 30 to 80%); also the c-Kit-negative cell line GI
      CA-N was slightly affected, suggesting that other STI-571 targets operate in
      regulating NB proliferation. In addition, c-Kit-positive cell lines SK-N-BE2(c)
      and HTLA230, grown in SCF only, remained sensitive (40 and 70% of growth
      inhibition, respectively), while, in the same conditions, proliferation of the c
      Kit-negative cell line GI-CA-N was not affected. Immunoprecipitation of c-Kit
      from cell lysates of SK-N-BE2(c) and HTLA230 cells grown in SCF and subsequent
      western blot analysis of the immunoprecipitates revealed a sharp decrease of c
      Kit phosphorylation after STI-571 treatment. These data demonstrate that both c
      Kit and SCF are preferentially expressed in vivo in the most aggressive
      neuroblastic tumors and that their signaling is active in promoting in vitro NB
      cell proliferation that can be selectively inhibited by treatment with STI-571.

PMID- 12800188
TI  - Spontaneously formed tumorigenic hybrids of Meth A sarcoma cells and macrophages
      in vivo.
AB  - We have recently demonstrated that malignant cells can hybridize with tissue
      macrophages in vitro, giving rise to tumorigenic hybrids. We now demonstrate that
      this can occur spontaneously in vivo as a result of fusion between inoculated
      Meth A sarcoma cells and host cells, presumably macrophages. Thus, from tumor
      cell suspensions prepared by collagenase perfusion and density centrifugation,
      hybrid cells could be isolated that were neoplastic but in contrast to Meth A
      expressed macrophage markers and had phagocytic capacity. Their morphologic
      features were intermediate between Meth A and macrophages. By taking advantage of
      a semiallogeneic experimental system by inoculation of Meth A cells from BALB/c
      (H-2 K(d)) into (BALB.K x BALB/c) F(1) (H-2(k/d)), hybrid cells from these tumors
      could be shown to express MHC antigens of both the Meth A and the host
      haplotypes. Hybrid cells grew faster than Meth A cells in vivo, indicating
      acquisition of growth-promoting properties through heterotypic cell fusion.

PMID- 12800189
TI  - Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl-2 and
      Bcl-xL antisense treatment.
AB  - Our study was designed to investigate the role of the anti-apoptotic proteins Bcl
      2 and Bcl-xL in the chemoresistance of cells derived from malignant pleural
      mesothelioma. First, we determined the basal expression levels of Bcl-2 and Bcl
      xL in mesothelioma cells and examined the effect of their downregulation by
      antisense oligonucleotides. Bcl-xL mRNA and protein could be readily detected in
      mesothelioma cell lines, whereas only low levels of Bcl-2 mRNA and protein were
      found. Preferential downregulation of either Bcl-xL alone or of Bcl-xL and Bcl-2
      simultaneously was achieved by treatment with antisense oligonucleotides 4259 and
      4625, respectively, whereas the expression of other apoptosis-relevant genes
      remained unaffected. Treatment with oligonucleotides 4259 or 4625 lowered the
      apoptosis threshold in ZL34 mesothelioma cells, as indicated by an increase in
      cell death accompanied by increased caspase-3-like activity, a decrease of the
      mitochondrial transmembrane potential and the cleavage of procaspase-7 and ICAD.
      In addition to the direct induction of apoptosis, antisense treatment sensitized
      ZL34 cells to the cytostatic effect of cisplatin and gemcitabine, with the
      combination of 4625 and cisplatin being the most effective. Our results
      demonstrate that Bcl-2 and Bcl-xL antisense treatment facilitates apoptosis in
      mesothelioma cells and suggest the use of Bcl-2/Bcl-xL bispecific antisense
      treatment in combination with cisplatin or gemcitabine for therapy of malignant
      pleural mesothelioma.

PMID- 12800191
TI  - Cadherin switching in ovarian cancer progression.
AB  - The roles of the cadherins in the progression of ovarian cancer to the late
      stages of the disease state when malignant cells have disseminated within the
      peritoneal cavity remain poorly understood. In view of these observations, we
      have undertaken a comprehensive survey of the cadherin subtypes present in normal
      ovarian surface epithelium and peritoneum and in the tumors and peritoneal
      effusions of women diagnosed with Stage I or Stage II primary ovarian cancer
      using a degenerate cloning strategy for sequences highly conserved among this
      family of cell adhesion molecules. On the basis of the nucleotide sequences of
      the resultant PCR products, multiple cadherin subtypes (E-, N-, P-cadherin, and
      cadherin-4, -6, and -11) were found to be present in these normal and malignant
      tissues and cells. P-cadherin was determined to be the predominant cadherin
      subtype in normal peritoneum, peritoneal effusions and Stage II tumor masses. An
      increase in P-cadherin mRNA and protein expression levels in ovarian tumor masses
      with progression to later stages of the disease state was confirmed by Northern
      and Western blot analysis, respectively. In addition, we have determined that the
      cadherin-associated protein, known as beta-catenin, is expressed in normal
      peritoneum, ovarian tumors and malignant cell effusions obtained from women with
      Stage I or Stage II cancer. Immunoprecipitation studies demonstrated that P
      cadherin was capable of interacting with beta-catenin in these normal and
      malignant tissues and cells. Collectively, these findings suggest that the
      regulated expression of P-cadherin/beta-catenin complexes in ovarian tumor cells
      may represent a key step in disease progression.

PMID- 12800190
TI  - Ectopic chromosome around centrosome in metaphase cells as a marker of high-risk
      human papillomavirus-associated cervical intraepithelial neoplasias.
AB  - This report describes the appearance of ectopic chromosome around centrosome
      (ECAC) in metaphase cell nuclei of high-risk HPV-associated cervical neoplasms.
      ECAC are clearly visible on HE-stained sections as a tiny (approx. 0.7 micro),
      round, dark structure or an aggregate of filamentous chromosome, often
      symmetrical at bilateral centrosomes. They appear in CINs from an early stage
      (CIN I), with the highest incidence in HPV16-associated CIN II-III (75%), and are
      less common in HPV-related invasive carcinomas (21%) and in lesions associated
      with high-risk HPV types other than 16. Rates for ECAC-positive nuclei in
      metaphase preparations (ECAC rate) for each lesion ranged 3.6-30%, the average
      being 14.5%. ECAC appeared very rarely in CINs associated with intermediate-risk
      HPVs and was never encountered in HPV6/11-induced condylomas or HPV-unrelated
      neoplasms in other organs. ECAC may be morphologic evidence of HPV-induced
      chromosomal instability working as a background mechanism in cervical
      carcinogenesis and also a useful marker for the histopathologic differentiation
      of high-risk CINs.

PMID- 12800192
TI  - Vitamin D enhances caspase-dependent and -independent TNFalpha-induced breast
      cancer cell death: The role of reactive oxygen species and mitochondria.
AB  - Calcitriol, the hormonal form of vitamin D, potentiates the activity of some
      common anticancer drugs and agents of the anticancer immune system, including
      tumor necrosis factor alpha (TNFalpha). TNFalpha-induced cytotoxicity is due to
      both caspase-dependent and -independent pathways. Cotreatment with calcitriol
      enhanced both modes of TNFalpha-induced death in MCF-7 breast cancer cells. It
      increased caspase-3-like activity as assayed by the cleavage of poly-(ADP
      ribose)polymerase and of the fluorogenic substrate ac-DEVD-AMC. It also enhanced
      TNFalpha-induced caspase-independent cytotoxicity in the presence of the pan
      caspase inhibitor zD-2,6-dichlorobenzoyloxymethylketone. The antioxidants N
      acetylcysteine, reduced glutathione, lipoic acid and ascorbic acid markedly
      reduced the enhancing effect of the hormone on TNFalpha-induced caspase
      activation. N-acetylcysteine and reduced glutathione also decreased caspase
      independent cytotoxicity in the presence or absence of calcitriol, indicating
      that reactive oxygen species (ROS) have a key role in the cross talk between
      TNFalpha and calcitriol. Mitochondrial damage is common to both TNFalpha-induced
      caspase-dependent and -independent pathways and may underlie excessive production
      of ROS. Mitochondrial membrane potential (DeltaPsi) was assessed by the specific
      potential-sensitive fluorescent probe JC-1. The hormone augmented the drop in
      DeltaPsi and release of cytochrome c from mitochondria, induced by TNFalpha. The
      effect of calcitriol on DeltaPsi was mimicked by rotenone, which increased both
      the drop in DeltaPsi and caspase activation induced by TNFalpha. It is possible
      that the interaction of TNFalpha and calcitriol on the level of the mitochondria
      is the underlying mechanism responsible for the enhancement of TNFalpha-induced,
      ROS-mediated caspase-dependent and -independent cell death.

PMID- 12800193
TI  - Expression profiling of CC531 colon carcinoma cells reveals similar regulation of
      beta-catenin target genes by both butyrate and aspirin.
AB  - The CC531 cell line has been widely used to study different aspects of tumor
      growth and metastasis and provides an excellent experimental platform to develop
      novel antitumor strategies. To characterize the CC531 model at the molecular
      level, we screened for mutations in genes covering important signal-transduction
      pathways that are known to play major roles during colon carcinogenesis, the wnt
      and the ki-ras signaling pathways. We found both a prototypic beta-catenin
      (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing
      unambiguous evidence for the constitutive activation of these pathways in CC531
      cells. We further established comprehensive gene expression profiles of CC531
      cells and investigated the molecular response to 2 antitumor drugs, butyrate and
      aspirin. Using oligonucleotide microarrays, we screened the expression levels of
      7,700 genes and identified a total of 398 genes whose expression was
      significantly changed upon treatment with butyrate. When using aspirin, 121 genes
      were significantly altered. Interestingly, 36 genes were regulated by both
      butyrate and aspirin and 35 of them were regulated in the same direction. We
      found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos,
      Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras
      pathway. In all cases, butyrate and aspirin reversed the changes in expression
      normally found in response to active signaling of these oncogenic pathways. The
      microarray data are available (http://ncbi.nlm.nih.gov/geo/).

PMID- 12800195
TI  - Myeloperoxidase promotor polymorphism and risk of hepatoblastoma.
AB  - Myeloperoxidase (MPO) is a major enzyme found in neutrophils. Oxidation by MPO
      produces free radicals that demonstrate genotoxic properties. A polymorphism (G
      to A) within the promotor region of the MPO gene reduces transcription and
      expression. This polymorphism is associated with a protective effect against some
      cancers in adults including lung cancer. The objective of our study was to
      investigate the effect of this MPO polymorphism on the risk of hepatoblastoma,
      the most common cancer of the liver in childhood. By using PCR-SSCP, we
      determined the genotype at this polymorphism in 48 cases of Caucasian children
      with hepatoblastoma and 180 normal controls. Genotypes were confirmed by a second
      method using Aci I restriction enzyme restriction. We found that A allele was
      associated with reduced risk of hepatoblastoma of 50% (OR, 0.51; 95%CI, 0.27
      0.93) and G/A or A/A genotype reduced the risk by 56% (OR, 0.44; 95%CI, 0.21
      0.90). Our data suggest that A allele is a protective factor with regard to the
      risk of hepatoblastoma, perhaps by altering genotoxic properties of xenobiotic
      substances which may act as carcinogens.

PMID- 12800194
TI  - Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast
      cancer.
AB  - TMS1 (target of methylation-induced silencing) is a CpG island-associated gene
      that functions in the regulation of apoptosis and encodes a caspase recruitment
      domain, a recently described motif found in apoptotic signaling molecules. Recent
      evidence suggests that silencing of genes in the apoptotic pathway contribute to
      human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter
      in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by
      methylation-specific polymerase chain reaction (MSP) and its mRNA expression by
      reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of
      57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor
      tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40%
      (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines
      and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the
      peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as
      well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues
      7% (2 of 30). DNA methylation was confirmed by sequence analysis and the
      methylation status correlated inversely with TMS1 RNA expression in 18 cell lines
      tested. RNA expression was restored by treatment with the demethylating agent 5
      aza-2'-deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1
      transcript. Our results suggest that methylation of TMS1 may play a role in the
      pathogenesis of small cell and non small lung and breast cancers.

PMID- 12800196
TI  - Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast
      cancer: relationships with abnormal E-cadherin and catenin expression and
      microsatellite instability.
AB  - The causes and functional consequences of E-cadherin (E-CD) loss in breast cancer
      are poorly understood. E-CD loss might act in concert with alterations in the
      APC/beta-catenin pathway to permit oncogenic beta-catenin signaling. To test this
      hypothesis, we have analyzed the presence of genetic and epigenetic alterations
      affecting E-CD (CDH1), APC and beta-catenin (CTNNB1) genes and the
      immunohistochemical expression of E-CD, beta- and gamma-catenin in a series of 46
      infiltrating lobular breast carcinomas (ILCs). Since 80% of ILCs featured
      complete loss of E-CD expression, we analyzed the molecular alterations
      responsible for E-CD inactivation in these tumors. We found that 10 of 46 (22%)
      cases harbored mutations in CDH1, including 1 case with 2 different mutations (1
      of which was germline). CDH1 was also inactivated by loss of heterozygosity (LOH;
      30/41, 73%) and promoter hypermethylation (19/46, 41%). Interestingly, LOH and
      mutations were also detected in the corresponding in situ lesions of the ILCs,
      implying that these alterations are early events in lobular cancer tumorogenesis.
      Additionally, the presence of a polymorphism in the CDH1 promoter was found to be
      inversely correlated with CDH1 mutations, but not with E-CD levels. We next
      examined whether alterations in the APC/beta-catenin pathway also occurred in the
      same series of ILCs. Although no CTNNB1 or APC mutations were detected, promoter
      methylation (25/46, 52%) and LOH (7/30, 23%) of APC were found. Moreover,
      methylation of APC and CDH1 occurred concordantly. However, beta- and gamma
      catenin were severely reduced or absent in 90% of these tumors, implying that
      alterations in CDH1 and APC genes do not promote beta-catenin accumulation in
      ILC. These molecular alterations were not associated with microsatellite
      instability. In summary, several different mechanisms (mutations, LOH,
      methylation) are involved in the frequent CDH1 inactivation in invasive and in
      situ lobular breast cancer. The same tumors also show genetic and epigenetic
      alterations of APC gene. However, altered CDH1 and APC genes do not promote beta
      catenin accumulation in this tumor type.

PMID- 12800197
TI  - Homozygous deletions scanning in tumor cell lines detects previously unsuspected
      loci.
AB  - High rates of loss of heterozygosity commonly affect multiple chromosomes in
      individual tumor types, yet the number of known tumor suppressor genes (TSGs)
      systematically mutated in the corresponding tumors is usually low. The search for
      homozygously deleted genome segments in tumor samples or cell lines has become a
      method of choice to identify major TSGs or to reveal their influence on the
      development of a given tumor type. Here, we report a detailed homozygous deletion
      (HD) profiling for 246 critical loci on a panel of 89 tumor cell lines containing
      significant subsets of lung, ovarian and head and neck squamous cell carcinomas.
      We found a total of 53 HDs affecting 17 loci. The major target for HDs was p16
      INK4A/p14-ARF (23/89, 26% of cases). Among the remaining alterations, HDs
      affecting TP73 or telomeric markers have never been previously described, whereas
      other HDs represent the first examples associating lesions of certain TSGs with a
      given tumor type (NF2 in lung and ovarian cells, STK11 in HELA cells). Overall,
      tumor cell lines established from ovarian or lung carcinomas displayed a
      surprising diversity of loci targeted by HDs with 7 and 6 loci involved,
      respectively. Our data suggest that, beside allelotyping or
      transcriptome/proteome studies, extensive HD profiling represents a promising
      approach for the detection of hitherto not implicated signalling pathways of
      tumorigenesis.

PMID- 12800198
TI  - Characterization of several leukemia-associated antigens inducing humoral immune
      responses in acute and chronic myeloid leukemia.
AB  - To design a specific immunotherapy for leukemia patients, the identification of
      leukemia-associated antigens (LAAs) is a pivotal step. Antileukemic effects after
      hematopoetic stem cell transplantation for myeloid leukemias are observed and
      might be related to the recognition of LAAs. Using the serological screening of
      an expression library (SEREX) of K562 cells, we identified 16 different clones
      encoding LAAs eliciting a humoral immune response, among them the heat shock
      proteins HSJ2 and HSP70, the M-phase phosphoprotein 11 (MPP11), the BRCA1
      associated protein (BRAP), the Jkappa recombination binding protein (RBPJkappa)
      and the receptor for hyaluronic acid mediated motility (RHAMM). Serological
      responses to MPP11 were observed in 7/19 (37%) of patients with acute myeloid
      leukemia (AML) and 6/16 (38%) of patients with chronic myeloid leukemia (CML),
      but not in healthy volunteers (0/20). IgG antibodies directed against MPP11 were
      also detected in 25-50% of the sera of patients with solid tumors such as
      melanoma, renal cell, ovarian and breast carcinoma. mRNA expression of MPP11 was
      detected in 20/20 AML patients and 7/10 patients with CML. In normal tissues,
      strong mRNA expression of MPP11 was only detected in testis. By real-time PCR, we
      detected upregulation of MPP11 in leukemic blasts. Simultaneous humoral immune
      responses to 2 or more of the 16 LAAs identified here was observed, suggesting
      the feasibility of a polyvalent vaccination as an option for immunotherapies in
      leukemia patients.

PMID- 12800199
TI  - Selective expression of HLA-G in malignant and premalignant skin specimens in
      kidney transplant recipients.
AB  - The HLA-G molecule has been implicated in the escape from the host antitumor
      immune response. Besides, this molecule appears also to be detected in transplant
      recipient's tissues, mainly those with fewer rejection episodes. Since skin
      carcinomas develop frequently in organ transplant recipients, we asked whether
      HLA-G could be expressed in these lesions, therefore allowing tumor development
      in such patients. Immunohistochemical analysis of kidney transplant recipients
      presenting various types of epithelial malignant tumor and benign cutaneous
      lesion was done using a specific anti-HLA-G antibody. HLA-G was expressed in 35%
      of specimens of SCC, 47% of in situ carcinoma, 27% of AK and 14% of BCC but never
      in the 24 benign lesions studied. Many benign specimens were obtained from the
      same patients who had tumors, demonstrating that HLA-G expression was restricted
      to the malignant sites. Interestingly, HLA-G was expressed by proliferative
      keratinocytes, inflammatory infiltrates and even endothelial cells. Cytokines
      triggered in the course of organ transplantation include IL-10. This molecule may
      induce expression of HLA-G, which in turn may be implicated in tumor development
      in transplanted recipients.

PMID- 12800200
TI  - NKT and CD8 lymphocytes mediate suppression of hepatocellular carcinoma growth
      via tumor antigen-pulsed dendritic cells.
AB  - Dendritic cells (DCs) are antigen presenting cells that play a role in T-cell
      activation. Liver-associated natural killer T lymphocytes (NKTs) are a unique
      subset of lymphocytes that may be important in antitumor immunity. Hepatitis B
      virus (HBV)-associated hepatocellular carcinoma (HCC) expresses hepatitis B virus
      surface antigen (HBsAg) on its cell surface and may serve as a tumor-associated
      antigen. The aim of the study was to evaluate the antitumor effect of DC pulsed
      with tumor or viral-associated antigens in HBV-expressing HCC in mice and to
      determine the role of NKT lymphocytes in this process. Balb/c mice were
      sublethally irradiated and transplanted with Hep3b HCC cell line, followed by
      transplantation of naive splenocytes. DCs were separated using CD11c beads and
      pulsed with HBV-enveloped proteins (group A), HCC cell lysate (group B), or BSA
      (control group C). Mice were followed for survival and tumor size. To determine
      the mechanism of the antitumor effect, intrasplenic and intrahepatic lymphocyte
      subpopulations were analyzed by FACS for NKT, CD4 and CD8 markers. Tumor
      associated antigens-specific IFNgamma ELISPOT, T-cell proliferation assays and
      serum cytokine analysis were performed. Treatment with tumor-associated antigen
      pulsed DC significantly improved survival (40% and 50% as compared with 0% in
      groups A, B, and control group C, respectively; p < 0.005). Tumor size decreased
      to 12.8 +/- 0.4 and 0 from 60.4 +/- 0.9 mm(3) in groups A, B, and control group
      C, respectively (p < 0.005). Adoptive transfer of HBV or Hep3b-associated
      antigens-pulsed DC induced a 6-fold increase in peripheral CD8(+) lymphocytes
      (from 1% in control mice to 6% and 5.5% in groups A and B, respectively), along
      with a decrease in CD4(+) lymphocytes (from 3.5% in controls to 1.4% and 2.3% in
      A and B, respectively; p < 0.005). The CD8(+)/CD4(+) ratio increased from 0.28 in
      controls to 4.28 and 2.39 in groups A and B, respectively (p < 0.005).
      Intrasplenic NKT cells increased from 7% in control mice to 7.98% and 14.6% in
      groups A and B, respectively. In contrast, an opposite shift was observed inside
      the liver. Intrahepatic lymphocyte analysis showed a marked increase in CD4(+)
      and a decrease in CD8(+) lymphocytes in treated groups. The intrahepatic CD4(+)
      number increased from 0.5% in controls to 2.15% and 25.8% in groups A and B,
      respectively (p < 0.005). In contrast, a significant decrease in the intrahepatic
      CD8(+) numbers was observed (from 7% in controls to 1.0% and 2.4% in groups A and
      B, respectively; p < 0.005). A significant increase was noted in HBV-specific
      IFNgamma spot-forming T-cell colonies from 0.0 to 8.8 +/- 1.7 and 1.8 +/- 2.9 in
      groups C, A, and B, respectively (p < 0.005). Similarly, a significant increase
      in the HBV-specific T-cell stimulation index, from 0.8 +/- 0.2 to 7.2 +/- 0.4, in
      groups C and B, respectively, was noted (p < 0.002). IFNgamma and IL12 serum
      levels increased significantly in treated groups. IFNgamma and IL12 serum levels
      increased to 380 +/- 30 and 400 +/- 20, and 960 +/- 40 and 760 +/- 60 in groups A
      and B, compared with 150 +/- 16 and 490 +/- 40 pg/ml in control mice (p < 0.005).
      Tumor antigen-pulsed DCs effectively suppressed the growth of hepatocellular
      carcinoma in mice. This effect was associated with enhanced NKT and CD8(+)
      lymphocyte function and augmentation of the antitumor/antiviral-specific IFNgamma
      production.

PMID- 12800201
TI  - Novel tumor antigens identified by autologous antibody screening of childhood
      medulloblastoma cDNA libraries.
AB  - Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By
      screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous
      sera, 15 different antigens were identified. These antigens were encoded by 3
      novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942,
      HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAP1,
      PRDM13) and genes encoding a motor protein (kinesin-2), a histone (H2A1.2), the
      ankyrin residue-rich nasopharyngeal cancer susceptibility protein (NZ16) and the
      transcription factor TZP, which is homologous to the tumor-associated antigens
      HCA58 and GLEA2. In a consecutive analysis of serum antibody titers and tumor
      load, a more than 10-fold increase in serum antibodies against PRDM13 preceded
      the clinical diagnosis of recurrent tumor growth in a patient with aggressive
      large cell medulloblastoma. When sera of pediatric patients with cancer (n = 40)
      and healthy controls (n = 40) were tested for humoral responses against the SEREX
      defined antigens, 5 antigens were exclusively recognized by sera from cancer
      patients. These antigens included a novel rab18 gene product translated from mRNA
      sequences formerly described as 3' untranslated region. Humoral responses against
      2 of the remaining 10 antigens were found preferentially in cancer patients.
      Antibodies against these antigens were detected in 8/40 and 12/40 cancer
      patients, respectively, but in only 1 healthy control. The 2 antigens were
      characterized by a tumor-specific deletion and a tumor-specific mutation,
      respectively. These findings indicate that the humoral immune response against
      medulloblastoma is directed against diverse antigens that may be useful as
      diagnostic markers or targets for immunotherapy.

PMID- 12800202
TI  - Malignant tumors in first-degree relatives of cancer patients aged 0-25 years
      (province of Trieste, Italy).
AB  - To determine whether the occurrence of first and second primary malignancies in
      first-degree relatives of cancer patients aged 0-25 years (probands) differed
      from that in the general population, a cohort study was carried out on 860
      relatives of 265 probands living in the province of Trieste, Italy. During the
      follow-up period (median duration = 28 years, 25th-75th percentile = 20-34), the
      relatives developed 103 first primary cancers vs. 88.9 expected for a
      standardized incidence ratio (SIR) of 1.2 (p = 0.2). Significantly elevated risks
      were found for melanoma in the parents of probands aged 15-25 years with melanoma
      (SIR = 15.0, p = 0.002), for hemolymphatic malignancies in the fathers of
      probands aged 0-14 years with brain tumors (SIR = 13.3, p = 0.0005) and for
      hemolymphatic cancers in relatives as a whole of probands aged 15-25 years with
      lymphomas (SIR = 4.5, p = 0.01). During the follow-up period, 7 relatives with a
      first primary cancer had a subsequent malignancy vs. 4.2 expected for an SIR of
      1.7 (p = 0.3). Our results indicate that young cancer patients per se should not
      to be considered as a factor that usually increases the risk of developing
      malignant tumors among their first-degree relatives, except when a known cancer
      family syndrome or predisposition is recognized.

PMID- 12800203
TI  - Familial brain tumours-genetics or environment? A nationwide cohort study of
      cancer risk in spouses and first-degree relatives of brain tumour patients.
AB  - Our study investigated whether the familial aggregation of glioma is due to
      environmental or genetic effects and it investigated and compared the risk to
      spouses and first-degree relatives (FDR) of patients with primary brain tumours
      (PBT) for developing both PBT and the risk for other types of cancer. All PBT
      patients identified in Sweden from 1958-97 in The Swedish Cancer Registry (SCR)
      were linked to the nationwide Swedish Family Database, including persons in
      Sweden born from 1932-97. The cohorts of spouses and FDR were linked to the SCR
      to identify observed cases of PBT and other cancer. Standardised incidence ratios
      (SIR) were calculated using the incidence rates from SCR as the reference. We
      found that there were no increased risks for any specific type of PBT in the
      cohort of spouses. In the FDR cohort, generally the risk for a PBT was
      significantly increased by 2 to 3 times for the same histopathology as the
      probands. Spouses of PBT patients had an increased risk of skin cancer. We
      conclude that FDR, not spouses, have a significantly increased risk, which
      indicates a genetic origin of the familial aggregation of brain tumours.

PMID- 12800204
TI  - Dietary influences on survival after ovarian cancer.
AB  - We evaluated the effects of various food groups and micronutrients in the diet on
      survival among women who originally participated in a population-based case
      control study of ovarian cancer conducted across 3 Australian states between 1990
      and 1993. This analysis included 609 women with invasive epithelial ovarian
      cancer, primarily because there was negligible mortality in women with borderline
      tumors. The women's usual diet was assessed using a validated food frequency
      questionnaire. Deaths in the cohort were identified using state-based cancer
      registries and the Australian National Death Index (NDI). Crude 5-year survival
      probabilities were estimated using the Kaplan-Meier technique, and adjusted
      hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox
      regression models. After adjusting for important confounding factors, a survival
      advantage was observed for those who reported higher intake of vegetables in
      general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third,
      compared to the lowest third), and cruciferous vegetables in particular (HR =
      0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third
      of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04).
      Inverse associations were also seen with protein (p-value trend 0.09), red meat
      (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive
      trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy
      products. Although much remains to be learned about the influence of nutritional
      factors after a diagnosis of ovarian cancer, our study suggests the possibility
      that a diet high in vegetable intake may help improve survival.

PMID- 12800205
TI  - Induced and spontaneous abortion and breast cancer risk: results from the E3N
      cohort study.
AB  - Recent reviews reach conflicting conclusions on breast cancer risk after
      spontaneous or induced abortion. E3N is a large-scale cohort study collecting
      detailed information on environmental and reproductive factors. We investigated
      the relation between breast cancer and a history of induced and/or spontaneous
      abortion, using the data from the 100,000 women aged 40-65 at entrance in 1990.
      Among them, over 2,600 new invasive breast cancers had been diagnosed by June
      2000. Multivariate analysis, adjusted for known potential confounders, showed no
      association between a history of induced abortion and breast cancer risk either
      in the whole population (relative risk [RR] = 0.91, 95% confidence interval [CI]
      0.82-0.99) or in subgroups defined by parity or by menopausal status. Overall,
      the association between spontaneous abortion and breast cancer was not
      significant (RR = 1.05, 95% CI 0.95-1.15). However, there is a suggestion of
      increased risk with increased number of miscarriages (RR = 1.20, 95% CI 0.92-1.56
      after 3 or more). Moreover, an interaction with menopausal status was observed.
      In premenopause, the risk decreased with increasing number of spontaneous
      abortions, whereas it increased in postmenopause. Among nulliparous and parous
      women, the relative risk estimates were respectively equal to 1.16 (95% CI 1.04
      1.30, p trend < 0.0008) and 1.14 (95% CI 1.01-1.28, p trend = 0.005).
      Premenopausal breast cancer, on the other hand, appeared to be less frequent in
      women who had had repeated miscarriages. We conclude that there is no
      relationship between breast cancer and induced abortion but that an association
      with spontaneous abortion is possible and may depend on menopausal status.

PMID- 12800206
TI  - Capsaicin consumption, Helicobacter pylori positivity and gastric cancer in
      Mexico.
AB  - Gastric cancer (GC) incidence has not declined in Mexico. We assessed whether the
      intake of capsaicin (CAP), the pungent compound of chili peppers, increases the
      risk of GC independently of H. pylori positivity (Hp). From 1994 to 1996, a
      hospital-based case-control study was performed in 3 areas of Mexico; 234 cases
      of GC and 468 matched controls were enrolled and their diet and other
      characteristics were inquired. Chili pepper intake was queried by interview and
      CAP content of chilies was determined in a separate analysis by gas
      chromatography to estimate CAP intake; IGg Hp serum antibodies were determined by
      ELISA. The risk of GC was increased (OR = 1.71; 95% CI = 0.76-3.88) among high
      level consumers of CAP (90-250 mg of capsaicin per day, approximately 9-25
      jalapeno peppers per day) as compared to low-level consumers (0-29.9 mg of
      capsaicin per day, approximately 0 to less than 3 jalapeno peppers per day; p for
      trend p = 0.026); this effect was independent of Hp status and other potential GC
      determinants and was higher among diffuse GC cases (OR = 3.64; 95% CI = 1.09
      12.2; p for trend = 0.002) compared to intestinal GC cases (OR = 1.36; 95% CI =
      0.31-5.89; p for trend = 0.493). No significant interaction was found between CAP
      intake and Hp on GC risk. Chili pepper consumption might be an independent
      determinant of GC in Mexico.

PMID- 12800207
TI  - Childhood exposure to simian virus 40-contaminated poliovirus vaccine and risk of
      AIDS-associated non-Hodgkin's lymphoma.
AB  - Persons with acquired immunodeficiency syndrome (AIDS) have increased risk for
      non-Hodgkin's lymphoma (NHL). Recent studies have reported the detection of DNA
      sequences from simian virus 40 (SV40), a macaque polyomavirus that contaminated
      early poliovirus vaccines, in a large proportion of AIDS-associated NHLs. To
      examine the association between SV40 exposure and NHL risk, we analyzed data from
      a U.S. registry-based cohort study of persons with AIDS (1980-96). We calculated
      NHL incidence in persons born in 1958-61 (exposed to SV40-contaminated poliovirus
      vaccine as children, n = 39,468) and in 1964-67 (born after vaccines were cleared
      of SV40 and thus unexposed, n = 17,340). Among persons with AIDS, NHL incidence
      was 11.7 per 1,000 person-years in SV40-exposed individuals (616 NHL cases) and
      10.1 per 1,000 person-years in SV40-unexposed individuals (230 cases; unadjusted
      relative risk 1.15, 95% CI 0.99-1.34, p = 0.06). Because of differences in
      cohorts' birth years and the evolving demographics of the AIDS epidemic, SV40
      exposed subjects were older at AIDS onset than unexposed subjects (mean age 32.0
      vs. 27.2 years, p < 0.0001), and the cohorts differed by sex (p < 0.0001) and
      ethnic group (p < 0.0001). Since NHL incidence was relatively high among whites
      (p < 0.0001) and homosexual males (p < 0.0001) and increased with age (p = 0.09),
      comparisons required adjustments for these factors. After adjustment, SV40
      exposure was not associated with NHL incidence (adjusted relative risk 0.97, 95%
      CI 0.79-1.20, p = 0.80). We conclude that childhood exposure to SV40 through
      receipt of contaminated poliovirus vaccine was not associated with increased risk
      for AIDS-associated NHL. Our findings do not support a role for SV40 in
      lymphomagenesis among immunosuppressed persons.

PMID- 12800208
TI  - Prognostic value of bcl-6, CD10 and CD38 immunoreactivity in stage I-II gastric
      lymphomas: identification of a subset of CD10+ large B-cell lymphomas with a
      favorable outcome.
AB  - bcl-6, CD10 and CD38 are useful markers for identifying 2 molecularly and
      prognostically distinct profiles of diffuse large B-cell lymphomas (LCLs),
      defined as germinal-center B-like and activated B-like. We investigated the
      prognostic role of bcl-6, CD10 and CD38 immunoreactivity in 102 gastrectomized
      patients with primary gastric lymphomas (PGLs). There were 41 low-grade marginal
      zone lymphomas of MALT-type (LGML) and 61 diffuse large B-cell lymphomas with
      (DLCLMLs; n = 31) or without (DLCLs; n = 30) an LGML component. bcl-6, CD10 and
      CD38 were significantly more commonly expressed in DLCL or DLCML as compared with
      LGML (50% vs. 48% vs. 17%, p = 0.0002 for bcl-6; 27% vs. 26% vs. 0%, p = 0.0004
      for CD10; 45% vs. 48% vs. 13%, p = 0.0005 for CD38, respectively). CD10
      immunoreactivity was independently associated with a better survival in diffuse
      LCL patients (5-year overall survival: 88% +/- 8% vs. 66% +/- 7%; p = 0.04); bcl
      6 or CD38 immunoreactivities did not disclose any prognostic implication. Age,
      presence of LGML component, lactic dehydrogenase serum levels and use of
      chemotherapy were additional independent prognostic factors. We conclude that
      CD10 immunoreactivity assessment could be a clear, easy-to-interpret and reliable
      prognostic factor in PGL. Accordingly, patients with CD10(+) gastric large B-cell
      lymphomas may be at reduced risk and eligible for clinical trials evaluating more
      conservative therapeutic options.

PMID- 12800209
TI  - Little evidence for involvement of MLH3 in colorectal cancer predisposition.
AB  - Mutations in the DNA MMR genes MSH2, MLH1, MSH6 and PMS2 underlie a large subset
      of HNPCC cases, and a hallmark of the tumors is MSI. In many HNPCC families,
      however, a causative mutation has not been found. Therefore, the involvement of
      additional, thus far unknown, genes in MSI as well as MSS colorectal tumor
      predisposition is possible. The role of a relatively recently cloned MMR gene,
      MLH3, in familial CRC has been studied; but the results appear somewhat
      conflicting. To further evaluate the role of MLH3 in CRC predisposition, we
      analyzed 30 Finnish CRC cases for germline mutations by sequencing. These cases
      were selected from a large series of Finnish CRC patients, to match features
      previously proposed to associate with MLH3 germline defects. We found 5 missense
      variants, 4 of which were also found in Finnish cancer-free controls. The only
      remaining variant does not appear to be an attractive candidate for a disease
      associated mutation because the amino acid change is located outside the
      conserved residues. We also screened for the previously reported variants,
      including a frameshift change, the most likely pathogenic MLH3 mutation observed
      so far. The frameshift was not present in the 30 CRC cases or in 700 cancer-free
      controls. While it is a difficult task to exclude a role of MLH3 in HNPCC, our
      study could not confirm a role for MLH3 in CRC predisposition.

PMID- 12800210
TI  - Are solid tumours different in children with Down's syndrome?

PMID- 12800212
TI  - Severe acute respiratory syndrome and its lesions in digestive system.
AB  - Severe acute respiratory syndrome (SARS) is an infectious atypical pneumonia that
      has recently been recognized in the patients in 32 countries and regions. This
      brief review summarizes some of the initial etiologic findings, pathological
      description, and its lesions of digestive system caused by SARS virus. It is an
      attempt to draw gastroenterologists and hepatologists' attention to this fatal
      illness, especially when it manifests itself initially as digestive symptoms.

PMID- 12800213
TI  - Advances in clinical diagnosis and treatment of severe acute respiratory
      syndrome.
AB  - It has been proved that severe acute respiratory syndrome (SARS) is caused by
      SARS-associated coronavirus, a novel coronavirus. SARS originated in Guangdong
      Province, the People's Republic of China at the end of 2002. At present, it has
      spread to more than 33 countries or regions all over the world and affected 8 360
      people and killed 764 by May 31,2003. Identification of the SARS causative agent
      and development of a diagnostic test are important. Detecting disease in its
      early stage, understanding its pathways of transmission and implementing specific
      prevention measures for the disease are dependent upon swift progress. Due to the
      efforts of the WHO-led network of laboratories testing for SARS, tests for the
      novel coronavirus have been developed with unprecedented speed. The genome
      sequence reveals that this coronavirus is only moderately related to other known
      coronaviruses. WHO established the definitions of suspected and confirmed and
      probable cases. But the laboratory tests and definitions are limited. Until now,
      the primary measures included isolation, ribavirin and corticosteroid therapy,
      mechanical ventilation, etc. Other therapies such as convalescent plasma are
      being explored. It is necessary to find more effective therapy. There still are
      many problems to be solved in the course of conquering SARS.

PMID- 12800214
TI  - Mechanism and its regulation of tumor-induced angiogenesis.
AB  - Tumor angiogenesis is the proliferation of a network of blood vessels that
      penetrates into cancerous growths, supplying nutrients and oxygen and removing
      waste products. The process of angiogenesis plays an important role in many
      physiological and pathological conditions. Solid tumors depend on angiogenesis
      for growth and metastasis in a hostile environment. In the prevascular phase, the
      tumor is rarely larger than 2 to 3 mm(3) and may contain a million or more cells.
      Up to this size, tumor cells can obtain the necessary oxygen and nutrient
      supplies required for growth and survival by simple passive diffusion. The
      properties of tumors to release and induce several angiogenic and anti-angiogenic
      factors which play crucial roles in regulating endothelial cell (EC)
      proliferation, migration, apoptosis or survival, cell-cell and cell-matrix
      adhesion through different intracellular signaling are thought to be the
      essential mechanisms during tumor-induced angiogenesis. Tumor angiogenesis
      actually starts with tumor cells releasing molecules that send signals to
      surrounding normal host tissue. This signaling activates certain genes in the
      host tissue that, in turn, make proteins to encourage growth of new blood
      vessels. In this review, we focus the mechanisms of tumor-induced angiogenesis,
      with an emphasis on the regulatory role of several angiogenic and anti-angiogenic
      agents during the angiogenic process in tumors. Advances in understanding the
      mechanisms of tumor angiogenesis have led to the development of several most
      effective anti-angiogenic and anti-metastatic therapeutic agents and also have
      provided several techniques for the regulation of cancer's angiogenic switch. The
      suggestion is made that standard cytotoxic chemotherapy and angiogenesis
      inhibitors used in combination may produce complementary therapeutic benefits in
      the treatment of cancer.

PMID- 12800215
TI  - Primary adenocarcinomas of lower esophagus, esophagogastric junction and gastric
      cardia: in special reference to China.
AB  - Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The
      pathogenesis, molecular changes in the early stage of carcinogenesis and related
      risk factors have not been well characterized. There is evidence, however, that
      GCA differs from cancer of the rest of the stomach in terms of natural history
      and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric
      junction (EGJ) and gastric cardia have been given much attention because of their
      increasing incidences in the past decades, which is in striking contrast with the
      steady decrease in distal stomach adenocarcinoma. In China, epidemiologically,
      GCA shares very similar geographic distribution with esophageal squamous cell
      carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province,
      North China, the highest incidence area of esophageal SCC in the world.
      Historically, both GCA and SCC in these areas were referred to as esophageal
      cancer (EC) by the public because of the common syndrome of dysphagia. In Western
      countries, Barrett's esophagus is very common and has been considered as an
      important precancerous lesion of adenocarcinoma at EGJ. Because of the low
      incidence of Barrett's esophagus in China, it is unlikely to be an important
      factor in early stage of EGJ adenocarcinoma development. However, Z line up
      growth into lower esophagus may be one of the characteristic changes in these
      areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a
      premalignant lesion for GCA is still not clear. Higher frequency of IM observed
      at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous
      lesion for GCA in these areas. Molecular information on GCA, especially in early
      stage, is very limited. The accumulated data about the changes of tumor
      suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially
      the similar alterations in GCA and SCC in the same patient, indicated that there
      might be some similar risk factors, such as nitrosamine, involved in both GCA and
      SCC in Henan population. The present observations also suggest that GCA should be
      considered as a distinct entity.

PMID- 12800216
TI  - DNA polymerase zeta: new insight into eukaryotic mutagenesis and mammalian
      embryonic development.
AB  - Information about the mechanisms that generate mutations in eukaryotes is likely
      to be useful for understanding human health concerns, such as genotoxicity and
      cancer. Eukaryotic mutagenesis is largely the outcome of attacks by endogenous
      and environmental agents. Except for DNA repair, cell cycle checkpoints and DNA
      damage avoidance, cells have also evolved DNA damage tolerance mechanism, by
      which lesion-targeted mutation might occur in the genome during replication by
      specific DNA polymerases to bypass the lesions (translesion DNA synthesis, TLS),
      or mutation on undamaged DNA templates (untargeted mutation) might be induced.
      DNA polymerase zeta (pol zeta), which was found firstly in budding yeast
      Saccharomyces cerevisiae and consists of catalytic subunit scRev3 and stimulating
      subunit scRev7, has received more attention in recent years. Pol zeta is a member
      of DNA polymerase eta subfamily, which belongs to DNA polymerase B family, and
      exists in almost all eukaryotes. Human homolog of the scRev3 gene is located in
      chromosome region 6q21, and the mouse equivalent maps to chromosome 10, distal to
      the c-myb gene and close to the Macs gene. Alternative splicing, upstream out-of
      frame ATG can be found in yeast scRev3, mouse and human homologs. Furthermore,
      the sequence from 253-323 immediate upstream of the AUG initiator codon has the
      potential to form a stem-loop hairpin secondary structure in REV3 mRNA,
      suggesting that human REV3 protein may be expressed at low levels in human cells
      under normal growth conditions. The functional domain analysis showed that yeast
      Rev3-980 tyrosine in conserved region II is at the polymerase active site. Human
      REV3 amino acid residues 1 776-2 195 provide a REV7 binding domain, and REV7
      amino acid residues 1-211 provide a bind domain for REV1, REV3 and REV7 itself.
      More interestingly, REV7 interacts with hMAD2 and therefore might function in the
      cell cycle control by affecting the activation of APC (anaphase promoting
      complex). Currently it has been known that pol zeta is involved in most
      spontaneous mutation, lesion-targeted mutation via TLS, chemical carcinogen
      induced untargeted mutation and somatic hypermutation of antibody genes in
      mammalian. In TLS pathway, pol zeta acts as a "mismatch extender" with
      combination of other DNA polymerases, such as pol iota. Unlike in yeast, it was
      found that pol zeta also functioned in mouse embryonic development more recently.
      It was hypothesized that the roles of pol zeta in TLS and cell cycle control
      might contribute to mouse embryonic lethality.

PMID- 12800217
TI  - Detection of human papillomavirus in Chinese esophageal squamous cell carcinoma
      and its adjacent normal epithelium.
AB  - AIM: To investigate the putative role of human papillomavirus (HPV) infection in
      the carcinogenesis of esophageal squamous cell carcinoma in China. METHODS:
      Twenty-three esophageal squamous cell carcinoma samples and the distal normal
      epithelium from Shanxi Province, and 25 more esophageal squamous cell carcinoma
      samples from Anyang city, two areas with a high incidence of esophageal cancer in
      China, were detected for the existence of HPV-16 DNA by PCR, mRNA in situ
      hybridization (ISH) and immunohistochemistry (IHC) targeting HPV-16 E6 gene.
      RESULTS: There were approximately 64 % (31/48) patients having HPV-16 DNA in
      tumor samples, among them nearly two-thirds (19/31) samples were detected with
      mRNA expression of HPV-16 E6. However, in the normal esophageal epithelium from
      cancer patients, the DNA and mRNA of HPV-16 were found with much less rate: 34.7
      % (8/23) and 26.1 % (6/23) respectively. In addition, at protein level detected
      by IHC assay, 27.1 % (13/48) tumor samples had virus oncoprotein E6 expression,
      while only one case of normal epithelium was found positive. CONCLUSION: HPV
      infection, especially type 16, should be considered as a risk factor for
      esophageal malignancies in China.

PMID- 12800218
TI  - Expression of ECRG4, a novel esophageal cancer-related gene, downregulated by CpG
      island hypermethylation in human esophageal squamous cell carcinoma.
AB  - AIM: To study the mechanisms responsible for inactivation of a novel esophageal
      cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).
      METHODS: A pair of primers was designed to amplify a 220 bp fragment, which
      contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR
      products of bisulfite-modified CpG islands were analyzed by denaturing high
      performance liquid chromatography (DHPLC), which were confirmed by DNA
      sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal
      cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal
      cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo
      kidney cell line-Hek293) and 2 normal esophagus tissues were detected. The
      expression level of the ECRG 4 gene in these samples was examined by RT-PCR.
      RESULTS: The expression level of ECRG 4 gene was varied. Of 20 esophageal cancer
      tissues, nine were unexpressed, six were lowly expressed and five were highly
      expressed compared with the adjacent tissues and the 2 normal esophageal
      epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A
      high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly
      expressed) of the 15 (80 %) downregulated cancer tissues and 3 of the 4
      unexpressed cell lines. No methylation peak was observed in the two highly
      expressed normal esophageal epithelia and the methylation frequency was low
      (3/20) among the 20 cases in the highly expressed adjacent tissues. The
      methylation status of the samples was consistent with the result of DNA
      sequencing. CONCLUSION: These results indicate that the inactivation of ECRG 4
      gene by hypermethylation is a frequent molecular event in ESCC and may be
      involved in the carcinogenesis of this cancer.

PMID- 12800219
TI  - Expression of a plant-associated human cancer antigen in normal, premalignant and
      malignant esophageal tissues.
AB  - AIM: To study the relationship between the expression profiles of a plant
      associated human cancer antigen and carcinogenesis of esophagus and its
      significance. METHODS: We analyzed expression of a plant-associated human cancer
      antigen in biopsy specimens of normal (n=29), mildly hyperplastic (n=29), mildly
      (n=30), moderately (n=27) and severely dysplastic (n=29) and malignant esophageal
      (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human
      cancer antigen was mainly confined to the cytoplasm and showed diffuse type of
      staining. Positive staining was absent or weak in normal (0/30) and mildly
      hyperplastic tissue samples (2/29), while strong staining was observed in severe
      dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference
      of its expression between normal mucosa and severely dysplastic tissues (P<0.001)
      or carcinoma in situ (P<0.001). Significant difference was also observed between
      mild dysplasia and severe dysplasia (P<0.001) or carcinoma in situ (P<0.001). An
      overall trend toward increased staining intensity with increasing grade of
      dysplasia was found. There was a linear correlation between grade of lesions and
      staining intensity (r=0.794, P<0.001). Samples from esophageal cancer showed no
      higher levels of expression than those in severely dysplastic lesions (P>0.05).
      CONCLUSION: The abnormal expression of this plant-associated human cancer antigen
      in esophageal lesions is a frequent and early finding in the normal-dysplasia
      carcinoma sequence in esophageal carcinogenesis. It might contribute to the
      carcinogenesis of esophageal cancer. The abnormal expression of this plant
      associated human cancer antigen in esophageal lesion tissues may serve as a
      potential new biomarker for early identification of esophageal cancer.

PMID- 12800220
TI  - Upregulated expression of Ezrin and invasive phenotype in malignantly transformed
      esophageal epithelial cells.
AB  - AIM: To investigate the correlation between ezrin expression and invasive
      phenotype formation in malignantly transformed esophageal epithelial cells.
      METHODS: The experimental cell line employed in the present study was originated
      form the progressive induction of a human embryonic esophageal epithelial cell
      line (SHEE) by the E6E7 genes of human papillomavirus (HPV) type 18. The cells at
      the 35(th) passage after induction called SHEEIMM were in a state of immortalized
      phase and used as the control, while that of the 85(th) passage denominated as
      SHEEMT represented the status of cells that were malignantly transformed. The
      expression changes of ezrin and its mRNA in both cell passages were respectively
      analyzed by RT-PCR and Western blot. Invasive phenotype was assessed in vivo by
      inoculating these cells into the severe combined immunodeficient (SCID) mice via
      subcutaneous and intraperitoneal injection, and in vitro by inoculating them on
      the surface of the amnion membranes, which then was determined by light
      microscopy and scanning electron microscopy. RESULTS: Upregulated expression of
      ezrin protein and its mRNA was observed in SHEEMT compared with that in SHEEIMM
      cells. The SHEEMT cells inoculated in SCID mice were observed forming tumor
      masses in both visceral organs and soft tissues in a period of 40 days with a
      special propensity to invading mesentery and pancreas, but did not exhibit
      hepatic metastases. Pathologically, these tumor cells harboring larger nucleus,
      nucleolus and less cytoplasm could infiltrate and destroy adjacent tissues. In
      the in vitro study, the inoculated SHEEMT cells could grow in cluster on the
      amniotic epithelial surface and intrude into the amniotic stroma. In contrast,
      unrestricted growth and invasiveness were not found in SHEEIMM cells in both in
      vivo and in vitro experiment. CONCLUSION: The upregulated ezrin expression is one
      of the important factors that are possibly associated with the invasive phenotype
      formation in malignantly transformed esophageal epithelial cells.

PMID- 12800221
TI  - Research and control of well water pollution in high esophageal cancer areas.
AB  - AIM: In order to detect risk factors for esophageal cancer, a national research
      program was carried out during the Eighth Five-Year Plan (from 1991 to 1995).
      METHODS: Cixian County and Chichen County in Hebei Province were selected as the
      index and the control for the study fields with higher or lower incidence of
      esophagus cancer in China, respectively. In these areas, we investigated the
      pollution of three nitrogenous compounds in well water for drinking and the use
      of nitrogen fertilizer in farming. RESULTS: In well water, nitrate nitrogen,
      nitrite nitrogen and ammonia nitrogen were 8.77 mg/L, 0.014 mg/L and 0.009 mg/L
      in Cixian County in 1993, respectively. They were significantly higher than their
      levels (3.84 mg/L, 0.004 mg/L and 0.004 mg/L) in Chichen County (P<0.01, t=6.281,
      t=3.784, t=3.775). There was a trend that the nitrogenous compounds in well water
      increased from 1993 to 1996. The amount of nitrogen fertilizer used in farming
      was 787.6 kg per hectare land in Cixian County in 1991, significantly higher than
      186 kg per hectare in Chichen County (t=9.603, P<0.001). CONCLUSION: These
      investigations indicate that the pollution of nitrogenous compounds in well water
      for drinking is closely related to the use of nitrogen fertilizer in farming, and
      there is a significantly positive correlation between the level of three
      nitrogenous compounds in well water and the mortality of esophageal cancer
      (correlation coefficient =0.5992). We suggest that improvement of well system for
      drinking water quality should be an effective measure for esophageal cancer
      prevention and control in rural areas.

PMID- 12800222
TI  - Development of an oral DNA vaccine against MG7-Ag of gastric cancer using
      attenuated salmonella typhimurium as carrier.
AB  - AIM: To develop an oral DNA vaccine against gastric cancer and evaluate its
      efficacy in mice. METHODS: The genes of the MG7-Ag mimotope and a universal Th
      epitope (Pan-DR epitope, PADRE) were included in the PCR primers. By PCR, the
      fusion gene of the two epitopes was amplified. The fusion gene was confirmed by
      sequencing and was then cloned into pcDNA3.1(+) plasmid. The pcDNA3.1 (+)
      MG7/PADRE was used to transfect an attenuated Salmonella typhimurium. C57BL/6
      mice were orally immunized with 1X10(8) cfu Salmonella transfectants. Salmonella
      harboring the empty pcDNA3.1(+) plasmid and phosphate buffer saline (PBS) were
      used as negative controls. At the 6th week, serum titer of MG7-Ag specific
      antibody was detected by ELISA. At the 8th week cellular immunity was detected by
      an unprimed proliferation test of the spleenocytes by using a ((3)H)-thymidine
      incorporation assay. Ehrlich ascites carcinoma cells expressing MG7-Ag were used
      as a model in tumor challenge assay to evaluate the protective effect of the
      vaccine. RESULTS: Serum titer of antibody against MG7-Ag was significantly higher
      in mice immunized with the vaccine than that in control groups (0.841 vs 0.347,
      P<0.01; 0.841 vs 0.298, P<0.01), while in vitro unprimed proliferation assay of
      the spleenocytes showed no statistical difference between those three groups. Two
      weeks after tumor challenge, 2 in 7 immunized mice were tumor free, while all the
      mice in the control groups showed tumor formation. CONCLUSION: Oral DNA vaccine
      against the MG7-Ag momitope of gastric cancer is immunogenic. It can induce
      significant humoral immunity against tumor in mice, and the vaccine has partially
      protective effects.

PMID- 12800223
TI  - A gene encoding an apurinic/apyrimidinic endonuclease-like protein is up
      regulated in human gastric cancer.
AB  - AIM: To identify the gene that may predispose to human gastric cancer and to
      analyze its expression in gastric cancer and non-tumorous gastric mucosa.
      METHODS: Cancer, para-tumor, and non-tumor gastric tissues were studied for gene
      expression profile using fluorescent differential display reverse transcription
      polymerase chain reaction (DDRT-PCR). The differentially expressed bands of
      interest were analyzed by cloning, Northern blotting, and sequencing. The
      sequencing results were compared with the GenBank database for homology and
      conserved domain analysis. In situ hybridization with DIG-labeled cRNA probes was
      used to detect the expression of gene in paraffin embedded gastric adenocarcinoma
      and non-cancerous tissues. RESULTS: A gene expressed higher in tumor and para
      tumor tissues than in their non-tumor counterparts of all 7 tested gastric
      adenocarcinoma patients was identified by means of DDRT-PCR analysis. It was
      named GCRG213 (gastric cancer related gene 213). Northern blot confirmed the
      differential expression. GCRG213 (GenBank No. AY053451) consisted of 1094 base
      pairs with an open reading frame (ORF) which encoded 142 amino acids. The deduced
      amino acid sequence contained a putative conserved domain, apurinic/apyrimidinic
      endonuclease (APE). In situ hybridization analysis showed that GCRG213 was
      expressed higher in gastric cancer tissues than in their corresponding non-tumor
      ones. Precancerous leisions of gastric adenocarcinoma showed a high GCRG213
      expression, too. No difference of the expression patterns was found between the
      early and advanced gastric cancer. CONCLUSION: A gene named GCRG213 was
      identified in human gastric adenocarcinoma. It encoded an APE-like protein which
      was probably a new member of the APE family. GCRG213 was over-expressed not only
      in gastric cancer, but also in its precancerous leisions. The role of GCRG213
      expression in carcinogenesis needs further study.

PMID- 12800224
TI  - Is p53 gene mutation an indicatior of the biological behaviors of recurrence of
      hepatocellular carcinoma?
AB  - AIM: To evaluate mutant p53 gene in primary hepatocellular carcinoma and to
      investigate the correlation between it and the recurrence of hepatocellular
      carcinoma. METHODS: Mutations of p53 gene were examined using anti-human p53
      monoclonal antibody and immunohistochemical staining in 79 resected
      hepatocellular carcinomas. The correlations among variables of p53 positivity and
      invasiveness, disease free interval and survival were studied. In addition, in
      those who developed recurrence, the correlation among p53 positivity, clinical
      features and post-recurrence survival were also studied. RESULTS: Of these 79
      cases, 64 (81 %) had p53 mutation. Those patients with mutant p53 positivity had
      significantly more tumor recurrence (76.6 % vs 40.0 %, P=0.0107). However, the
      COX proportional hazards model showed that p53 overexpression had only weak
      correlations with recurrence free interval and survival time (P=0.088 and 0.081),
      which was probably related to the short duration of follow-up. The invasiveness
      variables may be predictors of HCC recurrence. On univariate analysis, more
      patients with mutant p53 positivity had vascular permeation (78.1 vs 40.0 %,
      P=0.0088, O.R. (odds ratio) =5.3), grade II-IV differentiation (98.4 vs 80.0 %,
      P=0.0203, O.R. =15.7), no complete capsule (82.8 vs 53.3 %, P=0.0346, O.R. =4.2)
      and daughter nodules (60.9 vs. 33.3 %, P=0.0527, O.R. =3.1) than patients with
      negative p53 staining. On multivariate analysis, only vascular permeation and
      grade of differentiation remained significant (P=0.042 and 0.012). There was no
      statistically significant correlation between the status of p53 in the primary
      lesion and the clinical features of recurrent hepatocellular carcinomas examined,
      including extrahepatic metastasis (P=0.1103) and the number of recurrent tumors
      (P=1.000) except for disease over more than one segment in the extent of
      recurrent tumors (P=0.0043). The post-recurrence median survival was lower in
      patients in whom p53 mutation had been detected in the primary lesion with a weak
      significance (3.42 months vs 11.0 months, P=0.051). CONCLUSION: Our findings
      suggest that p53 mutation correlates significantly with invasiveness including
      vascular permeation, grade of cellular differentiation, incomplete capsule and
      multinodular lesions. Hepatocellular carcinomas with p53 mutations had more tumor
      recurrence and p53 mutation may also influence disease recurrence interval and
      survival time. Hepatocellular carcinomas with p53 mutations recur more
      extensively with a shorter survival. Therefore, p53 mutation in the primary
      lesion is useful as an indicator of the biological behavior of recurrent
      hepatocellular carcinomas.

PMID- 12800225
TI  - Transcatheter arterial embolization treatment in patients with hepatocellular
      carcinoma and risk of pulmonary metastasis.
AB  - AIM: To investigate the relationship between transcatheter arterial embolization
      (TAE) and pulmonary metastasis in subjects with hepatocellular carcinoma (HCC).
      METHODS: A total of 287 patients with HCC followed up for more than 1 week were
      included. 102 patients underwent transcatheter arterial embolization (TAE group)
      and 185 received conservative treatment (control group). The patients' chest x
      rays and chest CT scans were examined for pulmonary metastasis. RESULTS: Patients
      with TAE had a median survival of 19.3 months while that of the control group was
      only 10.0 months (P<0.05). Pulmonary metastasis occurred in 14 (13.7 %) patients
      in the TAE group and 14 (7.6 %) patients in the control group, there was no
      significant difference (P>0.05). The 1-year, 2-year and 5-year cumulative
      incidence of pulmonary metastasis was 11.8 %, 17.6 % and 24.0 % in the TAE group
      and 7.0 %, 13.0 % and 21.7 % in the control group, respectively (P>0.05). On the
      univariate analysis, tumor size, abnormal serum alanine aminotransferase levels
      and heterogeneity on sonography were significantly associated with pulmonary
      metastasis. However, on the multivariate analysis, only tumor size was
      significantly predictive of pulmonary metastasis. CONCLUSION: TAE is effective on
      prolonging survival of patients with HCC. It does not significantly increase the
      risk of pulmonary metastasis. Tumor size is the only significant predictive
      factor associated with lung metastasis.

PMID- 12800226
TI  - Changes in survival patterns in urban Chinese patients with liver cancer.
AB  - AIM: To examine the survival patterns and determinants of primary liver cancer in
      a geographically defined Chinese population. METHODS: Primary liver cancer cases
      (n=13 685) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer
      Registry. Age-adjusted and age-specific incidence rates were examined in both
      males and females. Proportional hazards (Cox) regression was utilized to explore
      the effects of time of diagnosis, sex, age, occupation, residence, and hospital
      of diagnosis on survival. RESULTS: Crude and age-adjusted incidence rates in the
      study period were: 27.4/100 000 and 26.3/100 000 in males; and 11.5/100 000 and
      10.4/100 000 in females, respectively. Cox regression analyses indicated that
      there was a significant improvement in survival rates over time. Industrial
      workers and older people had relatively poor survival rates. The hospital in
      which the liver cancer was diagnosed was a statistically significant predictor of
      survival; patients diagnosed in city hospitals were more likely to have better
      survival than those diagnosed in community/district hospitals. CONCLUSION:
      Patients diagnosed in recent years appeared to have a better outcome than those
      diagnosed in early times. There were also significant survival disparities with
      respect to occupation and hospital of diagnosis, which suggest that socioeconomic
      status may play an important role in determining prognosis.

PMID- 12800227
TI  - Loss of fragile histidine triad protein in human hepatocellular carcinoma.
AB  - AIM: To investigate the expression of fragile histidine triad (FHIT) gene
      protein, Fhit, which is recently thought to be a candidate tumor suppressor.
      Abnormal expression of fragile histidine triad has been found in a variety of
      human cancers, but little is known about its expression in human hepatocellular
      carcinogenesis and evolution. METHODS: Sections of 83 primary human
      hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10
      normal liver tissue were evaluated immunohistochemically for Fhit protein
      expression. RESULTS: All normal liver tissue and para-neoplastic liver tissue
      showed a strong expression of Fhit, whereas 50 of 83 (65.0 %) carcinomas showed a
      marked loss or absence of Fhit expression. The differences of Fhit expression
      between carcinoma and normal or para-neoplastic liver tissue were highly
      significant (P=0.000). The proportion of carcinomas with reduced Fhit expression
      showed an increasing trend (a) with decreasing differentiation or higher
      histological grade (P=0.219); (b) in tumors with higher clinical stage III and IV
      (91.3 %, P=0.000), compared with tumors with lower stage I and II (27.6 %); and
      (c) in cancers with bigger tumor size (>50 mm) (75.0 %, P=0.017), compared with
      smaller tumor size (< or = 50 mm). CONCLUSION: FHIT inactivation seems to be both
      an early and a later event, associated with carcinogenesis and progression to
      more aggressive hepatocellular carcinomas. Thus, evaluation of Fhit expression by
      immunohistochemistry in hepatocellular carcinoma may provide important diagnostic
      and prognostic information in clinical application.

PMID- 12800228
TI  - PPARgamma pathway activation results in apoptosis and COX-2 inhibition in HepG2
      cells.
AB  - AIM: To investigate whether troglitazone (TGZ), the peroxisome proliferator
      activated receptor (PPAR) gamma ligand, can induce apoptosis and inhibit cell
      proliferation in human liver cancer cell line HepG2 and to explore the molecular
      mechanisms. METHODS: (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT), ((3)H) Thymidine incorporation, Hochest33258 staining, DNA ladder,
      enzyme-linked immunosorbent assay (ELISA), RT-PCR, Northern and Western blotting
      analyses were employed to investigate the effect of TGZ on HepG2 cells and
      related molecular mechanisms. RESULTS: TGZ was found to inhibit the growth of
      HepG2 cells and to induce apoptosis. During the process, the expression of COX-2
      mRNA and protein and Bcl-2 protein was down-regulated, while that of Bax and Bak
      proteins was up-regulated, and the activity of caspase-3 was elevated.
      Furthermore, the level of PGE(2) was decreased transiently after 12 h of
      treatment with 30 microM troglitazone. CONCLUSION: TGZ inhibits cell
      proliferation and induces apoptosis in HepG2 cells, which may be associated with
      the activation of caspase-3-like proteases, down-regulation of the expression of
      COX-2 mRNA and protein, Bcl-2 protein, the elevation of PGE2 levels, and up
      regulation of the expressions of Bax and Bak proteins.

PMID- 12800229
TI  - Clinical significance of vascular endothelial growth factor expression and
      neovascularization in colorectal carcinoma.
AB  - AIM: To clarify the association of vascular endothelial growth factor (VEGF) and
      microvascular density (MVD) expression with the angiogenesis and prognosis of
      colorectal cancer. METHODS: A total of 97 cases of colorectal carcinomas were
      examined by immunohistochemical staining (SP method), using anti-VEGF and anti
      factor CD34(+) monoclonal antibodies. RESULTS: VEGF positive staining was
      obtained in 68 out of 97 cases (70.1 %), and observed mainly in the cytoplasm of
      tumor cells, and also frequently in stromal cells. VEGF expression was more
      intense in poorly differentiated adenocarcinoma in comparison with others, but
      there was no significant correlation between VEGF expression and age, sex and
      stage. A significant correlation was found between the MVD and grades, and there
      was no significant relationship between the MVD and age, sex, and stage. The MVD
      in the VEGF positive group (68 cases) was higher than that in the negative group.
      Upon multivariate analysis, the significant variables were stage, tumor grade and
      MVD; VEGF expression was not an independent prognostic factor. CONCLUSION: The
      expression of VEGF has a significant correlation with MVD; MVD expression has
      prognostic value but VEGF has not in colon cancer.

PMID- 12800230
TI  - Effects of KAI1/CD82 on biological behavior of human colorectal carcinoma cell
      line.
AB  - AIM: To investigate the effects of KAI1/CD82 on biological behavior of colorectal
      carcinoma cells. METHODS: KAI1 cDNA was transfected into highly malignant
      colorectal carcinoma cell line, LoVo, which had low level of endogenous KAI1
      expression, and established stable transfectant clones with high KAI1/CD82
      expression. The cell-cell adhesion, cell aggregation, cell-matrix adhesion and
      cell invasion assay were performed to determine whether KAI1 transfectant could
      have an effect on proliferation, adhesion and tumor metastasis in comparison with
      the control transfectant cells. RESULTS: KAI1 expression did not alter in vitro
      cell proliferation. But the KAI1 transfectant cells exhibited significantly
      increased homotypic cell-cell adhesion and cell aggregation in comparison with
      the control transfectant cells(P<0.05). Furthermore, KAI1 expression
      significantly suppressed the cell adhesion to extracellular matrix components and
      in vitro cell invasion in KAI1-transfected LoVo cells. The data indicated that
      KAI1 expression significantly suppressed the metastatic potential of KAI1
      transfected LoVo cells. CONCLUSION: Our results suggest that KAI1 might function
      as a negative regulator of colorectal carcinoma metastasis.

PMID- 12800231
TI  - Cyclooxygenase-2 expression and angiogenesis in colorectal cancer.
AB  - AIM: Cyclooxygenase-2 is involved in a variety of important cellular functions,
      including cell growth and differentiation, cancer cell motility and invasion,
      angiogenesis and immune function. However, the role of cyclooxygenase-2 as an
      angiogenic factor in colorectal cancer tissue is still unclear. We investigated
      the relationship between cyclooxygenase-2 and angiogenesis by analyzing the
      expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its
      association with vascular endothelial growth factor (VEGF) and microvascular
      density (MVD). METHODS: The expression of cyclooxygenase-2, VEGF, as well as MVD
      was detected in 128 cases of colorectal cancer by immunohistochemical staining.
      The relationship between the cyclooxygenase-2 and VEGF expression and MVD was
      evaluated. Our objective was to determine the effect of cyclooxygenase-2 on the
      angiogenesis of colorectal cancer tissue. RESULTS: Among 128 cases of colorectal
      cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %),
      respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7
      (standard deviation, 19.8). The expression of cyclooxygenase-2 was correlated
      significantly with the depth of invasion, stage of disease, metastasis (lymph
      node and liver), VEGF expression and MVD. Patients in T3-T4, stage III-IV and
      with metastasis had much higher expression of cyclooxygenase-2 than patients in
      T1-T2, stage I-II and without metastasis (P<0.05). The positive expression rate
      of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in
      the cyclooxygenase-2 negative group (18.4 %, P<0.05). Also, the microvessel count
      (56+/-16) in cyclooxygenase-2 positive group was significantly higher than that
      in cyclooxygenase-2 negative group (43+/-12, P<0.05). The microvessel count in
      tumors with positive cyclooxygenase-2 and VEGF was the highest (60+/-18, 41-142,
      P<0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF was the
      lowest (39+/-16, 23-68, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated
      with tumor progression by madulating the angiogenesis in colorectal cancer tissue
      and used as a possible biomarker.

PMID- 12800232
TI  - Synergistic antitumor effect of TRAIL and doxorubicin on colon cancer cell line
      SW480.
AB  - AIM: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) has been
      reported to specifically induce apoptosis of cancer cells although only a small
      percentage of cell lines were sensitive to it. Cell lines not responding to TRAIL
      in vitro were said to be more prone to apoptosis when TRAIL was combined with
      another anticancer agent. Generally, factors affecting drug-sensitivity involve
      many apoptosis-related proteins, including p53. The expression of wild-type p53
      gene was proposed as an important premise for tumor cells responding to
      chemotherapy. The present study was to investigate the cell killing action of
      TRAIL on colon cancer cell line SW480, its synergistic effect with doxorubicin,
      and the possible mechanisms. METHODS: SW480 cells were cultured in the regular
      condition and incubated with different levels of agents. Morphologic changes in
      these cells after treatment were observed under phase-contrast microscope and
      cytotoxicity by TRAIL alone and in combination with doxorubicin was quantified by
      a 1-day microculture tetrazolium dye (MTT) assay. In addition, flow cytometry
      assay (FCM) and transmission electron microscopy were used to detect apoptosis
      among these cells. Variation of p53 protein level among different groups
      according to concentrations of agents was measured by Western blot assay.
      RESULTS: (1) SW480 cells were not sensitive to TRAIL, with IC(50)>1 mg/L(-1) and
      dose-independent cytotoxicity. (2) SW480 cells were sensitive to doxorubicin at a
      certain degree, with dose-dependent cytotoxicity and IC(50)=65.25+/-3.48
      micromol/L(-1). (3) TRAIL could synergize with doxorubicin to kill SW480 cells
      effectively, which was represented by the boosted killing effect of doxorubicin
      on theses cells. IC(50) of doxorubicin against SW480 cells sharply reduced when
      it was combined with TRAIL. (4) Subtoxic TRAIL (100 microg/L(-1)), combined with
      subtoxic doxorubicin (0.86 micromol/L(-1)), could kill SW480 cells sufficiently.
      Cytotoxicity by MTT assay arrived at 80.12+/-2.67 %, which was significantly
      higher than that by TRAIL or doxorubicin alone, with P=0.006 and 0.003
      respectively. This killing effect was partly due to apoptosis. It was proved by
      large amounts of apoptotic cells under phase-contrast microscopy, cell apoptosis
      rate of 76.82+/-1.93 % by FCM assay and typical apoptotic morphology observed
      through transmission electron microscopy. Increase of apoptosis after combined
      treatment had no relation with protein level of p53 (P>0.05). CONCLUSION: SW480
      cells are not sensitive to TRAIL, but TRAIL can synergize with lower
      concentration of doxorubicin to induce apoptosis effectively. The status of p53
      protein is not involved in the mechanism of synergistic apoptosis. It suggests
      the potential therapeutic applicability of the combination of TRAIL with
      doxorubicin against colon cancers.

PMID- 12800233
TI  - Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma
      carcinoma sequence.
AB  - AIM: To investigate the expression of inducible nitric oxide synthase (iNOS) in
      aberrant crypt foci (ACF) -adenoma-carcinoma sequence and its relation with tumor
      cell apoptosis, proliferation and angiogenesis. METHODS: The expression of iNOS,
      proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) in
      different stages of colorectal cancer were studied by immunohistochemical method
      from 30 normal tissues, 30 nonhyperplastic ACF, 30 hyperplastic ACF, 30
      dysplastic ACF, 30 adenomas and 60 carcinomas. The apoptotic cells were detected
      by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) method using an Apop Tag in situ detection kit. RESULTS: The
      immunoreactivity of iNOS significantly increased in the transition from
      hyperplastic ACF to dysplastic ACF. This transition was associated with a
      significant decrease in the apoptotic index (AI) (0.73+/-0.37 vs 0.61+/-0.35,
      P<0.05) and significant increases in the PCNA labeling index (LI) (27.3+/-2.80 vs
      40.3+/-3.11, P<0.01) and microvessel density (MVD) (55+/-11.5 vs 70+/-13.2,
      P<0.01). The expression of iNOS was in low levels and positively correlated with
      PCNA-LI (r=0.812, P<0.01) and MVD (r=0.863, P<0.01) during transition from normal
      mucosa to nonhyperplastic ACF and hyperplastic ACF. The expression of iNOS was in
      high levels and positively correlated with AI (r=0.901, P<0.01) after transition
      from hyperplastic ACF to dysplastic ACF, adenoma and carcinoma. CONCLUSION: The
      results suggest that the transition from hyperplastic ACF to dysplastic ACF may
      be a crucial step in the ACF-adenoma-carcinoma sequence, in which iNOS plays an
      important role by regulating tumor cell apoptosis, proliferation and
      angiogenesis.

PMID- 12800234
TI  - Distribution and anti-HBV effects of antisense oligodeoxynucleotides conjugated
      to galactosylated poly-L-lysine.
AB  - AIM: To describe distribution of the phosphorothioated antisense
      oligodeoxynucleotides (PS-asODNs) conjugated to galactosylated poly-L-lysine (Gal
      PLL) in mice, and to observe their effects on expression of HBV gene in the
      2.2.15 cells and transgenic mice. METHODS: According to the result of direct
      sequencing of PCR amplified products, a 16 mer phosphorothioate analogue of the
      antisense oligodeoxynucleotides (PS-asODNs) directed against the HBV U(5)-like
      region was conjugated to the hepatotropic Gal-PLL molecules. Its distribution was
      demonstrated using asODNs labeled with (32)P at the 5' terminus with a T4
      polynucleotide Kinase. Its inhibition effect on HBV expression was observed in
      the transfected 2.2.15 cells and transgenic mice. RESULTS: The Gal-PLL and asODNs
      could form stable complex at a molar ratio of 2:1. As shown in the HBV
      transfected 2.2.15 cells, the inhibition effects of asODNs alone and asODNs
      conjugated to Gal-PLL, at 10 micromol/L for both, on HBsAg and HBeAg production
      were different,the former being 70 % and 58 %, respectively, and the latter being
      96 % and 82 %, respectively. A more pronounced reduction was also observed in
      viral DNA load in the culture supernatant for the test with Gal-PLL-asODNs. Among
      many mouse organs, livers retained more asODNs molecules after administration.
      The preferential concentration in liver was found to be 52.14 % for Gal-PLL
      asODNs, as high as 2.38-fold of that for asODNs (21.9 %). Both elements decreased
      gradually in liver, with 2.9 % of the former, 5.99 % of the latter retained 24
      hours after the administration. The injection interval, therefore, was
      recommended to be 24 hours. In the transgenic mice, serum HBsAg decreased
      significantly (P<0.01) at the 12th day after administrating Gal-PLL- asODNs, the
      serum HBV DNA turned negative in 4 of the 6 mice. CONCLUSION: Antisense
      oligodeoxynucleotides conjugated to Gal-PLL can be concentrated in liver and
      intaked by hepatocytic cells. This may result in specific inhibition of
      expression and replication of HBV in vitro and in vivo.

PMID- 12800235
TI  - Cross-reactivity of hypervariable region 1 chimera of hepatitis C virus.
AB  - AIM: To analyze the amino acid sequences of hypervariable region 1 (HVR1) of HCV
      isolates in China and to construct a combinatorial chimeric HVR1 protein having a
      very broad high cross-reactivity. METHODS: All of the published HVR1 sequences
      from China were collected and processed with a computer program. Several
      representative HVR1's sequences were formulated based on a consensus profile and
      homology within certain subdivision. A few reported HVR1 mimotope sequences were
      also included for a broader representation. All of them were cloned and expressed
      in E.coli. The cross-reactivity of the purified recombinant HVR1 antigens was
      tested by ELISA with a panel of sera from HCV infected patients in China. Some of
      them were further ligated together to form a combinatorial HVR1 chimera. RESULTS:
      Altogether 12 HVR1(s) were selected and expressed in E.coli and purified to
      homogeneity. All of these purified antigens showed some cross-reactivity with
      sera in a 27 HCV positive panel. Recombinant HVR1s of No. 1, 2, 4, and 8# showing
      broad cross-reactivities and complementarity with each other, were selected for
      the ligation elements. The chimera containing these 4 HVR1s was highly expressed
      in E.coli. The purified chimeric antigen could react not only with all the HCV
      antibody positive sera in the panel but also with 90/91 sera of HCV -infected
      patients. CONCLUSION: The chimeric antigen was shown to have a broad cross
      reactivity. It may be helpful for solving the problem caused by high variability
      of HCV, and in the efforts for a novel vaccine against the virus.

PMID- 12800236
TI  - TT virus infection in patients with chronic hepatitis B and response of TTV to
      lamivudine.
AB  - AIM: To investigate the responses of TT virus (TTV) and hepatitis B virus (HBV)
      to a long-term lamivudine therapy. METHODS: Sixteen patients infected with both
      TTV and HBV were treated with lamivudine 100 mg daily for 30 months. Blood
      samples were drawn at the beginning of the therapy and subsequently at month 3,
      6, 9, 12 and 30. Serum TTV was quantified by real time PCR and serum HBV was
      detected by hybridization assay and nested polymerase chain reaction. RESULTS:
      TTV infection was detected in 100 % of HBV-infected patients. Loss of serum TTV
      DNA after one year of treatment occurred in 1/16 (6 %) patients. At the end of
      therapy, TTV DNA was positive in 94 % of them. The decline of HBV viremia was
      evident at 3 months after therapy and the response rate was 31 %, 44 %, 63 %, 50
      % and 50 % at month 3, 6, 9, 12 and 30, respectively. CONCLUSION: TTV replication
      is not sensitive to lamivudine and is highly prevalent in HBV-infected patients.

PMID- 12800238
TI  - Clinicopathologic study of mucosa-associated lymphoid tissue lymphoma in
      gastroscopic biopsy.
AB  - AIM: To explore and discuss the clinicopathologic characteristics of mucosa
      associated lymphoid tissue (MALT) lymphoma in gastroscopic biopsy specimen.
      METHODS: A retrospective study of 26 cases of lymphoma diagnosed by gastroscopic
      biopsy during 1999 to 2001 from gastroscopy files of Xijing Hospital was made.
      The diagnostic criteria were adopted according to the new classification of non
      Hodgkin's lymphoma. RESULTS: Twenty-six cases of primary gastric lymphoma
      consisting of 15 men and 11 women, aged between 23 to 76 years were recruited
      from 6 225 cases who received gastroscopy. All of them were diagnosed by both
      endoscopic findings and histological examinations. Histologically, 23 cases were
      MALToma (low grade) and 3 cases lymphoblastic lymphoma (high grade).
      Immunohistochemically, all cases were CD20 positive, while CK and EMA were
      negative. CONCLUSION: The majority of the cases of primary low-grade gastric
      lymphoma have morphologic and clinical features that justify their inclusion in
      the category of low-grade lymphoma of mucosa associated lymphoid tissue.

PMID- 12800237
TI  - Antralization at the edge of proximal gastric ulcers: does Helicobacter pylori
      infection play a role?
AB  - AIM: To determine the prevalence of antralization at the edge of proximal gastric
      ulcers, and the effect of H. pylori eradication on the mucosal appearances.
      METHODS: Biopsies were taken from the antrum, body and the ulcer edge of patients
      with benign proximal gastric ulcers before and one year after treatment. Gastric
      mucosa was classified as antral, transitional or body type. H. pylori positive
      patients received either triple therapy, or omeprazole. RESULTS: Patients with
      index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type
      mucosa was more prevalent at the ulcer edge in H. pylori-positive patients than
      H. pylori-negative patients (93 % vs 60 %, OR=8.95, 95 %CI: 2.47-32.4, P=0.001).
      At one year, there was a significant reduction in the prevalence of antralization
      (from 93 % to 61 %, P=0.004) at the ulcer edge in patients with H. pylori being
      eradicated. However, there was no difference in the prevalence of antralization
      at the ulcer edge in those with persistent infection. CONCLUSION: H. pylori
      infection is associated with antralization at the edge of proximal gastric
      ulcers, which may be reversible in some patients after eradication of the
      infection.

PMID- 12800239
TI  - Expression and cell-specific localization of cholecystokinin receptors in rat
      lung.
AB  - AIM: To elucidate whether CCK receptors exist in lung tissues and their precise
      cellular localization in the lung. METHODS: CCK-AR and CCK-BR mRNA expression and
      cellular distribution in the rat lung were detected by highly sensitive method of
      in situ reverse transcription-polymerase chain reaction (RT-PCR) and conventional
      in situ hybridization. RESULTS: CCK-AR and CCK-BR gene positive signals were
      observed in bronchial epithelial cells, alveolar epithelial cells, pulmonary
      macrophages and vascular endothelial cells of the rats' lung by in situ RT-PCR.
      The hybridization signals of CCK-AR were relatively faint. By in situ
      hybridization, however, only the signals of CCK-BR but not CCK-AR were detected
      in the lung, and the positive staining was only found in vascular endothelial
      cells and macrophages. CONCLUSION: CCK-AR and CCK-BR gene were present in
      pulmonary vascular endothelial cells, macrophages, bronchial epithelial cells and
      alveolar epithelial cells, which play an important role in mediating the
      regulatory actions of CCK-8 on these cells.

PMID- 12800240
TI  - Effect of caffeic acid phenethyl ester on proliferation and apoptosis of hepatic
      stellate cells in vitro.
AB  - AIM: To investigate the role of nuclear factor-kappaB (NF-kappaB) inhibitor
      caffeic acid phenethy1 ester (CAPE) in the proliferation, collagen synthesis and
      apoptosis of hepatic stellate cells (HSCs) of rats. METHODS: The HSCs from rats
      were isolated and cultured in Dulbecco's Modified Eagle's Medium (DMEM) and
      treated with CAPE. The proliferation and collagen synthesis of HSCs were
      determined by (3)H-TdR and (3)H-proline incorporation respectively, and the
      expression of type I, III procollagen genes was further explored by in situ
      hybridization. Apoptosis cell indices (AIs) were examined using terminal
      deoxynucleotidyl transferase- mediated DIG-dUTP nick end labeling (TUNEL).
      RESULTS: In activated HSC in culture, CAPE significantly inhibited (3)H-TdR and
      (3)H-proline incorporation by HSCs at concentrations of 5 micromol/L and 10
      micromol/L respectively. CAPE also reduced the type I procollagen gene expression
      (P<0.05) at higher concentration. Apoptosis of HSC was induced by CAPE and the
      AIs were time-and dose-dependently increased from 2.82+/-0.73 % to 7.66+/-1.25 %
      at 12 h (P<0.01) and from 3.15+/-0.88 % to 10.61+/-2.88 % at 24 h (P<0.01).
      CONCLUSION: CAPE inhibits proliferation and collagen synthesis of HSC at lower
      concentration and induces HSC apoptosis at higher concentration.

PMID- 12800241
TI  - Isolation and analysis of a novel gene over-expressed during liver regeneration.
AB  - AIM: To isolate and analyze a novel gene over-expressed during liver
      regeneration. METHODS: Total RNA of regenerating liver was extracted from liver
      tissue after 0-4-36-36-36 hr short interval successive partial hepatectomy
      (SISPH). Reverse transcription-polymerase chain reaction was used to synthesize
      double strand cDNA, after the tissue was digested by proteinase K and Sfi A/B.
      The double-strand cDNA was ligated to lambdaTriplEx2. lambdaphage packaging
      reaction was performed and E. coli XL1-Blue was infected for titering and
      amplifying. One expressed sequence tag was probed by Dig and phage in situ
      hybridization was carried out to isolate positive clones. Positive recombinant
      lambdaTriplEx2 was converted to the corresponding pTriplEx2, and bioinformatics
      was used to analyze full-length cDNA. RESULTS: We isolated a novel full-length
      cDNA during liver regeneration following SISPH. CONCLUSION: We have succeeded in
      cloning a novel gene, based on bioinformatics. We postulate that this gene may
      function in complicated network in liver regeneration. On the one hand, it may
      exert initiation of liver regeneration via regulating nitric oxide synthesis. On
      the other hand, it may protect damaged residue lobus following SISPH.

PMID- 12800242
TI  - Expression of insulin-like growth factor 1 and insulin-like growth factor 1
      receptor and its intervention by interleukin-10 in experimental hepatic fibrosis.
AB  - AIM: To study the expression of IGF-1 and IGF-1R and its intervention by
      interleukin-10 in the course of experimental hepatic fibrosis. METHODS: Hepatic
      fibrosis was induced in rats by carbon tetrachloride intoxication and liver
      specimens were taken from the rats administered CCl4 with or without IL-10
      treatment and the animals of the control group. Immunoreactivities for insulin
      like growth factor-1 (IGF-1) and IGF-1 receptor(IGF-1R) were demonstrated by
      immunohistochemistry, and their intensities were evaluated in different animal
      groups. RESULTS: The positive levels for IGF-1 and IGF-1R were increased with the
      development of hepatic fibrosis, with the positive signals localized in cytoplasm
      and/or at the plasmic membrane of hepatocytes. The positive signals of IGF-1 and
      IGF-1R were observed more frequently (P<0.01) in the CCl4-treated group (92.0 %
      and 90.0 %) compared to those in the control group. The positive signals
      decreased significantly (P<0.05) in IL-10-treated group. The responses in IGF-1
      and IGF-1R expression correlated with the time of IL-10 treatment. CONCLUSION:
      The expression of IGF-1 and IGF-1R immunoreactivities in liver tissue seems to be
      up-regulated during development of hepatic fibrosis induced by CCl(4), and
      exogenic IL-10 inhibits the responses.

PMID- 12800243
TI  - Experimental study of effect of Ganyanping on fibrosis in rat livers.
AB  - AIM: To observe the effects of Ganyanping on CCl(4)-induced hepatic fibrosis in
      rats. METHODS: The rats were separated randomly into five groups. Groups A to
      group D, each consisting of 15 rats, were for different tests, while 8 rats were
      used as normal controls (N). For group D, CCl(4) was injected subcutaneously, at
      a dosage of 3 ml/kg for 9 weeks. For group A, Ganyanping was administered via
      gastric tube at a dosage of 10 ml/kg. For group B, the treatment with Ganyanping
      was started 4 weeks after CCl(4) administration. In group C, Ganyanping was
      administered 8 weeks after the intoxication, and treatment lasted for 4 weeks.
      Liver tissues were fixed in 10 % formalin and embedded in paraffin. Pathologic
      changes, particularly fibrosis, were evaluated on the HE and V-G-stained
      sections. Ten middle-power fields were randomly selected for assessment of
      collagen deposition. RESULTS: Loss of normal hepatic architecture, some with
      pseudo-lobule formation, was observed in group D, while hepatocytes steatosis and
      fibrosis were less pronounced in the animals treated with Ganyanping. Pseudo
      lobule formation was not evident in the latter groups. The total collagen area
      and ratio were 840.23+/-81.65 and 7.0+/-0.9, respectively in group D, the ratio
      being reduced greatly in the Ganyanping-treated groups (148.73+/-45.89 and 1.16+/
      0.33, respectively). The activities of MAO and ACP were elevated and that of SDH
      in group D decreased in the hepatic tissue as compared to the control group. The
      treatment with Ganyanping abrogated these enzymatic changes. CONCLUSION: Our data
      approved that Ganyanping could improve the microcirculation in the liver, reduce
      oxygen-derived free radicals, and enhance the cellular metabolism and immune
      function, all resulting in an anti-fibrotic effect. Hence, Ganyanping can protect
      the liver from fibrosis. It may be a safe and effective preparation for patient
      with fibrosis.

PMID- 12800244
TI  - NF-kappaB activation and zinc finger protein A20 expression in mature dendritic
      cells derived from liver allografts undergoing acute rejection.
AB  - AIM: To investigate the role of NF-kappaB activation and zinc finger protein A20
      expression in the regulation of maturation of dendritic cells (DCs) derived from
      liver allografts undergoing acute rejection. METHODS: Sixty donor male SD rats
      and sixty recipient male LEW rats weighing 220-300 g were randomly divided into
      whole liver transplantation group and partial liver transplantation group.
      Allogeneic (SD rat to LEW rat) whole and 50 % partial liver transplantation were
      performed. DCs from liver grafts 0 hour and 4 days after transplantation were
      isolated and propagated in the presence of GM-CSF in vitro. Morphological
      characteristics and phenotypical features of DCs propagated for 10 days were
      analyzed by electron microscopy and flow cytometry, respectively. NF-kappaB
      binding activity, IL-12p70 protein and zinc finger protein A20 expression in
      these DCs were measured by EMSA and Western blotting, respectively. Histological
      grading of rejection was determined. RESULTS: Allogeneic whole liver grafts
      showed no signs of rejection on day 4 after the transplantation. In contrast,
      allogeneic partial liver grafts demonstrated moderate to severe rejection on day
      4 after the transplantation. After propagation for 10 days in the presence of GM
      CSF in vitro, DCs from allogeneic whole liver grafts exhibited features of
      immature DC with absence of CD40 surface expression, these DCs were found to
      exhibit detectable but very low level of NF-kappaB activity, IL-12 p70 protein
      and zinc finger protein A20 expression. Whereas, DCs from allogeneic partial
      liver graft 4 days after transplantation displayed features of mature DC, with
      high level of CD40 surface expression, and as a consequence, higher expression of
      IL-12p70 protein, higher activities of NF-kappaB and higher expression of zinc
      finger protein A20 compared with those of DCs from whole liver grafts (P<0.001).
      CONCLUSION: These results suggest that A20 expression is up-regulated in response
      to NF-kappaB activation in mature DCs derived from allogeneic liver grafts
      undergoing acute rejection. Given the NF-kappaB inhibition function of this gene,
      it is suggested that their expression survives to limit NF-kappaB activation and
      maturation of DCs, and consequently inhibits the acute rejection and induces
      acceptance of liver graft.

PMID- 12800245
TI  - Celecoxib inhibits proliferation and induces apoptosis via prostaglandin E2
      pathway in human cholangiocarcinoma cell lines.
AB  - AIM: To evaluate the roles and mechanisms of celecoxib in inducing proliferation
      inhibition and apoptosis of human cholangiocarcinoma cell lines. METHODS:
      Cyclooxygenase-2-overexpressing human cholangiocarcinoma cell line QBC939 and
      cyclooxygenase-2-deficient human cholangiocarcinoma cell line SK-CHA-1 were used
      in the present study. The anti-proliferative effect was measured by
      methabenzthiazuron (MTT) assay; apoptosis was determined by transferase-mediated
      dUTP nick end labeling (TUNEL) detection and transmission electron microscopy
      (TEM). Cell cycle was analyzed by flow cytometry (FCM). The PGE(2) levels in the
      supernatant of cultured cholangiocarcinoma cells were quantitated by enzyme
      linked immunoabsordent assay (ELISA). RESULTS: Celecoxib suppressed the
      production of PGE(2) and inhibited the growth of QBC939 cells. Celecoxib at 10,
      20, and 40 micromol/L inhibited PGE(2) production by 26 %, 58 %, and 74 % in
      QBC939 cells. The PGE(2) level was much lower constitutively in SK-CHA-1 cells
      (18.6+/-3.2) compared with that in QBC939 (121.9+/-5.6) cells (P<0.01) and
      celecoxib had no significant influence on PGE(2) level in the SK-CHA-1 cells. The
      PGE(2) concentration in SK-CHA-1 cells also reduced but not significantly after
      treatment with celecoxib. The PGE(2) concentration in SK-CHA-1 cells was (16.5+/
      2.9) ng/well, (14.8+/-3.4) ng/well, (13.2+/-2.0) ng/well and (12.6+/-3.1) ng/well
      respectively, when pre-treated with 1 micromol/L, 10 micromol/L, 20 micromol/L
      and 40 micromol/L of celecoxib for 48 h (P>0.05, vs control). The anti
      proliferation effect of celecoxib (20 micromol/L) on QBC939 cells was time
      dependent, it was noticeable on day 2 (OD490=0.23+/-0.04) and became obvious on
      day 3 (OD490=0.31+/-0.07) to day 4 (OD490= 0.25+/-0.06), and the OD490 in the
      control group (day 1) was 0.12+/-0.03 (P<0.01, vs control). The anti
      proliferation effect of celecoxib could be abolished by the addition of 200 pg/mL
      PGE(2). The proliferation of SK-CHA-1 cells was inhibited slightly by celecoxib,
      the cell density OD490 in the presence of celecoxib and in control group was
      0.31+/-0.04 and 0.42+/-0.03 respectively on day 2 (P>0.05), 0.58+/-0.07 and
      0.67+/-0.09 respectively on day 3 (P>0.05), and 0.71+/-0.08 and 0.78+/-0.06
      respectively on day 4 (P>0.05). Celecoxib induced proliferation inhibition and
      apoptosis by G(1)-S cell cycle arrest: the percentage of QBC939 cells in G(0)
      G(1) phase after treatment with 40 micromol/L (74.66+/-6.21) and 20 micromol/L
      (68.63+/-4.36) celecoxib increased significantly compared with control cells
      (54.41+/-5.12, P<0.01). The percentage of SK-CHA-1 cells in G(0)-G(1) phase after
      treatment with various concentrations of celecoxib didn't change significantly
      compared with control cells. The TUNEL index was much higher in QBC939 cells
      treated with 20 micromol/L celecoxib for 2 d (0.063+/-0.018) and for 4 d (0.102+/
      0.037) compared with control cells (0.017+/-0.004, P<0.01). CONCLUSION: The
      current in vitro study indicates that inhibition of proliferation and induction
      of apoptosis in human cholangiocarcinoma cells by cyclooxygenase-2 specific
      inhibitor celecoxib may involve in COX-dependent mechanisms and PGE(2) pathway.
      Celecoxib as a chemopreventive and chemotherapeutic agent might be effective
      primarily on COX-2-expressing cholangiocarcinoma.

PMID- 12800247
TI  - Rapid mitogen-activated protein kinase by basic fibroblast growth factor in rat
      intestine after ischemia/reperfusion injury.
AB  - AIM: Previous studies showed that exogenous basic fibroblast growth factor (bFGF
      or FGF-2) could improve physiological dysfunction after intestinal ischemia/
      reperfusion (I/R) injury. However, the mechanisms of this protective effect of
      bFGF are still unclear. The present study was to detect the effect of bFGF on the
      activities of mitogen-activated protein kinase (MAPK) signaling pathway in rat
      intestine after I/R injury, and to investigate the protective mechanisms of bFGF
      on intestinal ischemia injury. METHODS: Rat intestinal I/R injury was produced by
      clamping the superior mesenteric artery (SMA) for 45 minutes and followed by
      reperfusion for 48 hours. Seventy-eight Wistar rats were used and divided
      randomly into sham-operated group (A), normal saline control group (B), bFGF
      antibody pre-treated group (C), and bFGF treated group (D). In group A, SMA was
      separated without occlusion. In groups B, C and D, SMA was separated and occluded
      for 45 minutes, then, released for reperfusion for 48 hours. After the animals
      were sacrificed, blood and tissue samples were taken from the intestine 45
      minutes after ischemia in group A and 2, 6, 24, and 48 hours after reperfusion in
      the other groups. Phosphorylated forms of p42/p44 MAPK, p38 MAPK and stress
      activated protein kinase/C-Jun N-terminal kinase (SAPK/JNK) were measured by
      immunohistochemistry. Plasma levels of D-lactate were examined and histological
      changes were observed under the light microscope. RESULTS: Intestinal I/R injury
      induced the expression of p42/p44 MAPK, p38 MAPK, and SAPK/JNK pathways and
      exogenous bFGF stimulated the early activation of p42/p44 MAPK and p38 MAPK
      pathways. The expression of phosphorylated forms of p42/p44 MAPK was primarily
      localized in the nuclei of crypt cells and in the cytoplasm and nuclei of villus
      cells. The positive expression of p38 MAPK was localized mainly in the nuclei of
      crypt cells, very few in villus cells. The activities of p42/p44 MAPK and p38
      MAPK peaked 6 hours after reperfusion in groups B and C, while SAPK/JNK peaked 24
      hours after reperfusion. The activities of p42/p44 MAPK and p38 MAPK peaked 2
      hours after reperfusion in group D and those of SAPK/JNK were not changed in
      group B. D-lactate levels and HE staining showed that the intestinal barrier was
      damaged severely 6 hours after reperfusion; however, histological structures were
      much improved 48 hours after reperfusion in group D than in the other groups.
      CONCLUSION: The results indicate that intestinal I/R injury stimulates the
      activities of MAPK pathways, and that p42/p44 MAPK and p38MAPK activities are
      necessary for the protective effect of exogenous bFGF on intestinal I/R injury.
      The protective effect of bFGF on intestinal dysfunction may be mediated by the
      early activation of p42/p44 MAPK and p38 MAPK signaling pathways.

PMID- 12800246
TI  - Effects of melatonin on the expression of iNOS and COX-2 in rat models of
      colitis.
AB  - AIM: To investigate the effects of melatonin (MT) on the expression of inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of
      colitis. METHODS: Healthy adult Sprague-Dawlay (SD) rats of both sexes, weighing
      280+/-30 g, were employed in the present study. The rat models of colitis were
      induced by either acetic acid or 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      enemas. The experimental animals were randomly divided into melatonin treatment
      and model control group that were intracolicly treated daily with melatonin at
      doses of 2.5, 5.0, 10.0 mg/kg(-1) and equal amount of saline respectively from 24
      h following induction of colitis in rats inflicted with acetic acid enema and the
      seventh day in rats with TNBS to the end of study. A normal control group of rats
      treated with neither acetic acid nor TNBS but saline enema was also included in
      the study. On the 28(th) day of the experiment, the rat colon mucosal damage
      index (CDMI) was calculated, and the colonic prostaglandin E(2) (PGE(2)), nitric
      oxide (NO), as well as the iNOS and COX-2 expression were also determined
      biochemically or immunohistochemically. RESULTS: CDMI increased to 2.87+/-0.64
      and 3.12+/-1.12 respectively in rats treated with acetic acid and TNBS enema,
      which was in accordance with the significantly elevated colonic NO and PGE(2)
      contents, as well as the up-regulated colonic iNOS and COX-2 expression in both
      of the two rat models of colitis. With treatment by melatonin at the doses of 5.0
      and 10.0 mg/kg(-1), CDMI in both models of rat colitis was significantly
      decreased (P<0.05-0.01), which accorded synchronously and unanimously with the
      reduced colonic NO and PGE(2) content, as well as the down-regulated expression
      of colonic iNOS and COX-2. CONCLUSION: Melatonin has a protective effect on
      colonic injury induced by both acetic acid and TNBS enemas, which is probably via
      a mechanism of local inhibition of iNOS and COX-2 expression in colonic mucosa.

PMID- 12800248
TI  - Role of nitric oxide and peroxynitrite anion in lung injury induced by intestinal
      ischemia-reperfusion in rats.
AB  - AIM: To evaluate effects of nitric oxide (NO) and peroxynitrite anion (ONOO(-))
      on lung injury following intestinal ischemia-reperfusion (IR) in rats. METHODS: A
      rat model of intestinal ischemia was made by clamping superior mesenteric artery
      and lung injury was resulted from reperfusion. The animals were randomly divided
      into 3 groups: sham operation (Sham), 2 h ischemia followed by 2 h reperfusion
      (IR) and IR pretreated with aminoguanidine (AG) - an inhibitor of inducible NO
      synthase (iNOS) 15 minutes before reperfusion (IR+AG). The lung malondialdehyde
      (MDA) and nitrate/nitrite (NO(2)(-)/NO(3)(-)) contents and morphological changes
      were examined. Western blot was used to detect the iNOS protein expression.
      Immunohistochemical staining was used to determine the change of nitrotyrosine
      (NT)- a specific "footprint" of ONOO(-). RESULTS: The morphology revealed
      evidence for lung edema, hemorrhage and polymorphonuclear sequestration after
      intestinal IR. Compared with sham group, lung contents of MDA and NO(2)(-)/NO(3)(
      ) in IR group were significantly increased (12.00+/-2.18 vs 23.44+/-1.25 and
      76.39+/-6.08 vs 140.40+/-4.34, P<0.01) and the positive signals of iNOS and NT
      were also increased in the lung. Compared with IR group, the contents of MDA and
      NO(2)(-)/NO(3)(-) in IR+AG group were significantly decreased (23.44+/-1.25 vs
      14.66+/-1.66 and 140.40+/-4.34 vs 80.00+/-8.56, P<0.01) and NT staining was also
      decreased. CONCLUSION: Intestinal IR increases NO and ONOO(-) production in the
      lung, which may be involved in intestinal IR-mediated lung injury.

PMID- 12800249
TI  - Effects of n-3 fatty acid, fructose-1,6-diphosphate and glutamine on mucosal cell
      proliferation and apoptosis of small bowel graft after transplantation in rats.
AB  - AIM: To evaluate the effects of n-3 fatty acids (n-3FA), fructose-1,6-diphosphate
      (FDP) and glutamine (GLN) on mucosal cell proliferation and apoptosis of small
      bowel graft. METHODS: One hundred and ninety-six inbred strain Wistar rats were
      grouped as donors and recipients, and underwent heterotopic small bowel
      transplantation (SBT). n-3FA, FDP and GLN were administered via gastric tube as
      well as venous infusion for 10 days before and after surgery, respectively. The
      proliferation and apoptosis of mucosal cells were analyzed with flow cytometry
      and in situ cell death detection kits. RESULTS: Apparent apoptosis and minor
      proliferation of mucosal cells of small bowel graft after transplantation were
      observed. A higher mucosal cell proliferative index and lower apoptotic index
      were found in all small bowel grafts after supplying with n-3FA, FDP and GLN.
      CONCLUSION: Nutritional support with n-3FA, FDP and GLN promotes mucosal cell
      proliferation significantly, and prevents mucosal cell from undergoing apoptosis
      with different degrees. These regulatory effects on the apoptosis alter the
      structure and absorption function of transplanted small bowel favorably.

PMID- 12800250
TI  - Effects of glutamine on intestinal permeability and bacterial translocation in
      TPN-rats with endotoxemia.
AB  - AIM: To evaluate the protective effect and mechanism of glutamine on the
      intestinal barrier function in total parenteral nutrition (TPN) rats with trauma
      or endotoxemia. METHODS: To perform prospective, randomized and controlled animal
      experimentation of rats with surgical trauma, TPN and endotoxemia, thirty-four
      male, adult Sprague Dawley rats were divided into four groups: control group
      (n=8), TPN group (n=9), trauma and endotoxemia group (LPS, n=8) and trauma plus
      endotoxemia supplemented with glutamine in TPN solution group (Gln.group, n=9).
      All groups except the control group were given TPN solutions in 7-day
      experimental period. For Gln group, 1 000 mg/kg/d of glutamine was added to TPN
      solution during day 1-6. On the 7(th) day all the animals were gavaged with
      lactulose (66 mg) and mannitol (50 mg) in 2 ml of normal saline. Then 24 h urine
      with preservative was collected and kept at -20 degrees. On day 8, under intra
      peritoneal anesthesia using 100 mg/kg ketamin, the intestine, liver, mesenteric
      lymph nodes and blood were taken for examination. RESULTS: The body weight of LPS
      group decreased most among the four groups. The structure of small intestinal
      mucosa in TPN group, LPS group and Gln group showed impairments of different
      degrees, and the damage of small intestinal mucosa in Gln group was remarkably
      alleviated. The concentrations of interleukins in small intestine mucosa were
      lower (for IL-4 and IL-6) or the lowest (IL-10) in Gln group. The IgA level in
      the blood plasma and the mucosa of Gln group was the highest among all of the
      groups. The urine lactulose/mannitol test showed that the intestinal permeability
      in LPS group was lower than that in TPN group (P<0.001), but there was no
      difference between LPS group and Gln group. The rate of bacterial translocation
      in Gln group was lower than that in LPS group (P<0.02). CONCLUSION: Prophylactic
      treatment with glutamine could minimize the increments of intestinal permeability
      and bacterial translocation caused by trauma and endotoxemia in rats treated with
      TPN.

PMID- 12800251
TI  - Establishment of transgenic mice carrying the gene of human nuclear receptor
      NR5A2 (hB1F).
AB  - AIM: Human hepatitis B virus enhancer II B1 binding factor (hB1F) was cloned and
      characterized as a novel member of the Ftz-F1 (NR5A) nuclear receptor subfamily.
      Although progresses have recently been made, its biological function remains
      largely unidentified. The aim of this study was to establish an hB1F transgenic
      mouse model to promote the functional study of hB1F. METHODS: Transgene fragments
      were microinjected into fertilized eggs of mice. The manipulated embryos were
      transferred into the oviducts of pseudopregnant female mice. The offsprings were
      identified by PCR and Southern blot analysis. Transgene expression was analyzed
      with RT-PCR and Western blot analysis. Transgenic founder mice were used to
      establish transgenic mouse lineages. The F1 and F2 mice were identified by PCR
      analysis. RESULTS: Seven mice were identified as carrying copies of transgene. RT
      PCR and Western blotting results showed that the transgene was expressed in
      heart, liver, lung, kidney and stomach in one of the transgenic mouse lineages.
      Genetic analysis of the transgenic mice demonstrated that the transgene was
      integrated into the chromosome at a single site, and was transmitted stably.
      CONCLUSION: In this study we established an hB1F transgenic mouse model, which
      will facilitate the investigation of the biological function of hB1F in vivo.

PMID- 12800252
TI  - Gene-expression analysis of single cells-nested polymerase chain reaction after
      laser microdissection.
AB  - AIM: The structural and functional characteristics of cells are dependent on the
      specific gene expression profile. The ability to study and compare gene
      expression at the cellular level will therefore provide valuable insights into
      cell physiology and pathophysiology. METHODS: Individual cells were isolated from
      frozen colon tissue sections using laser microdissection. DNA as well as RNA were
      extracted, and total RNA was reversely transcribed to complementary DNA (cDNA).
      Both DNA and cDNA were analyzed by nested polymerase chain reaction (PCR). The
      quality of isolated DNA and RNA was satisfactory. RESULTS: Single cells were
      successfully microdissected using an ultraviolet laser micromanipulator. Nested
      PCR amplification products of DNA and cDNA of single cells could clearly be
      visualized by agarose gel electrophoresis. CONCLUSION: The combined use of laser
      microdissection and nested-PCR provides an opportunity to analyze gene expression
      in single cells. This method allows the analysis and identification of specific
      genes which are involved in physiological and pathophysiological processes in a
      complex of variable cell phenotypes.

PMID- 12800253
TI  - Rapid detection of the known SNPs of CYP2C9 using oligonucleotide microarray.
AB  - AIM: Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the
      metabolism of a large number of clinically important drugs. Individuals with
      mutant enzymes may risk serious side effects under routine therapy with certain
      drugs metabolized by CYP2C9. In order to facilitate the detection of the known
      SNPs of CYP2C9, an allele-specific oligonucleotide (ASO) based microarray was
      made. METHODS: An oligonucleotide microarray was made to facilitate the SNP
      (single nucleotide polymorphism) screening and was applied for the detection of
      CYP2C9 polymorphism in 62 high blood pressure (HBP) patients who received
      Irbesartan for treatment. Part of the genotyping results was confirmed by direct
      sequencing. And the relation between CYP2C9 polymorphism and therapeutic outcome
      of Irbesartan was statistically analyzed. RESULTS: Heterozygous alleles of
      CYP2C9*1/*3 were found in 7 out of 62 subjects. No mutant alleles of CYP2C9*2, *4
      and *5 and no homozygous mutant alleles were detected. The 7 heterozygous
      CYP2C9*1/*3 and 13 random wild type DNA samples were subjected to direct
      sequencing with purified PCR products and same genotyping results were obtained
      with the 20 DNA samples. There was no significant difference in the odds of
      effectiveness of Irbesartan between the wild type (normal) group and CYP2C9*1/*3
      (mutant) group (P>0.05). CONCLUSION: The oligonucleotide microarray made in this
      study is a reliable assay for detecting the CYP2C9 known alleles and the
      heterozygous CYP2C9*1/*3 has no significant effects on the therapeutic outcome of
      Irbesartan.

PMID- 12800254
TI  - Identification of RanBMP interacting with Shigella flexneri IpaC invasin by two
      hybrid system of yeast.
AB  - AIM: Bacillary dysentery caused by Shigella flexneri is still a threat to human
      health. Of four invasion plasmid antigen proteins (IpaA,B,C and D), IpaC plays an
      important role in the pathogenicity of this pathogen. The purpose of this study
      was to investigate the proteins interacting with IpaC in the host cell during the
      pathogenic process of this disease. METHODS: By applying two-hybrid system, the
      bait plasmid containing ipaC gene was constructed and designated pGBKT-ipaC. The
      bait plasmid was transformed AH109, and proved to express IpaC and then HeLa cDNA
      library plasmids were introduced into the above transformed AH109. The
      transformation mixture was plated on medium lacking Trp, Leu, and His in the
      initial screen, then restreaked on medium lacking Trp, Leu, His and Ade. Colonies
      growing on the selection medium were further assayed for beta-galactosidase
      activity. BLAST was carried out in the database after sequencing the inserted
      cDNA of the positive library plasmid. RESULTS: Among the 2X10(6) transformants,
      64 positive clones were obtained as determined by activation of His, Ade and LacZ
      reporter genes. Sequence analysis revealed that cDNA inserts of two colonies were
      highly homologous to a known human protein, RanBPM. CONCLUSION: These results
      provide evidence that IpaC may be involved in the invasion process of S. flexneri
      by interacting with RanBPM, and RanBPM is most likely to be the downstream target
      of IpaC in the cascade events of S. flexneri infection.

PMID- 12800255
TI  - Construction and expression of a humanized M2 autoantigen trimer and its
      application in the diagnosis of primary biliary cirrhosis.
AB  - AIM: To construct and express a humanized M(2) autoantigen trimer designated as
      BPO and to apply it in the diagnosis of primary biliary cirrhosis (PBC). METHODS:
      cDNA fragments encoding M(2)-reactive epitopes of pyruvate dehydrogenase complex
      E(2) (PDC-E(2)), branched chain 2-oxo-acid dehydrogenase complex E(2) (BCOADC
      E(2)) and 2-oxo-glutarate dehydrogenase complex E(2) (OGDC-E(2)) were amplified
      with PCR using total RNA extracted from human peripheral mononuclear blood cells.
      The fragments were cloned into the plasmid vector pQE-30 and then transferred
      into E. coli M15 (pREP4) for expression, which was induced by isopropylthio-beta
      D-galactoside. The expressed recombinant BPO protein was demonstrated by SDS
      PAGE, Western-blotting and Immunoabsorption test, its antigenic reactivity and
      specificity were identified with seven M(2)-positive sera confirmed at Euroimmun
      Research Center (Germany). Using the purified BPO, M(2) antibodies in sera from
      patients with PBC and other liver related diseases were detected with ELISA.
      RESULTS: The expressed BPO was observed with both antigenic reactivity and
      specificity of M(2) autoantigens. The determination of M(2) antibodies by BPO
      with ELISA was more sensitive than using the Euroimmun's kit with the
      coefficients of variation less than 10 % in both interassay and intraassay. With
      the newly established method, M(2) antibodies were found in 100 % (20/20) of
      patients with PBC. Six cases of liver disease with unknown etiology and 1 patient
      with drug induced liver injury had detectable levels of serum M(2) antibodies.
      There were also 2 patients with autoimmune cholangitis and 1 with autoimmune
      hepatitis showing M(2)-antibody positive. CONCLUSION: Compared with the routine
      immunofluorescence assay and commercially available assay kit using porcine heart
      mitochondrial protein as the antigen, the detection system established in the
      present study shows higher sensitivity and specificity and may be used as a
      powerful tool for the diagnosis of PBC.

PMID- 12800256
TI  - Functional brain imaging in irritable bowel syndrome with rectal balloon
      distention by using fMRI.
AB  - AIM: Irritable bowel syndrome (IBS) is characterized by abdominal pain and
      changes in stool habits. Visceral hypersensitivity is a key factor in the
      pathophysiology of IBS. The aim of this study was to examine the effect of rectal
      balloon-distention stimulus by blood oxygenation level-dependent functional
      magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the
      distribution, extent, and intensity of activated areas between IBS patients and
      normal controls. METHODS: Twenty-six patients with IBS and eleven normal controls
      were tested for rectal sensation, and the subjective pain intensity at 90 ml and
      120 ml rectal balloon-distention was reported by using Visual Analogue Scale.
      Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon
      distention in all subjects. RESULTS: Rectal distention stimulation increased the
      activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal
      cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon
      distention, the activation area and percentage change in MR signal intensity of
      the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in
      patients with IBS than that in controls. Score of pain sensation at 90 ml and 120
      ml rectal balloon-distention was significantly higher in patients with IBS than
      that in controls. CONCLUSION: Using fMRI, some patients with IBS can be detected
      having visceral hypersensitivity in response to painful rectal balloon
      distention. fMRI is an objective brain imaging technique to measure the change in
      regional cerebral activation more precisely. In this study, IC and PFC of the IBS
      patients were the major loci of the CNS processing of visceral perception.

PMID- 12800257
TI  - Tuberculosis of pancreas and peripancreatic lymph nodes in immunocompetent
      patients: experience from China.
AB  - AIM: To determine the clinical, radiographic and laboratory characteristics,
      diagnostic methods, and therapeutic variables in immunocompetent patients with
      tuberculosis (TB) of the pancreas and peripancreatic lymph nodes. METHODS: The
      records of 16 patients (6 male, 10 female; mean age 37 years, range 18-56 years)
      with tuberculosis of the pancreas and peripancreatic lymph nodes from 1983 to
      2001 in the Southwest Hospital were analyzed retrospectively. In addition, 58
      similar cases published in Chinese literature were reviewed and summarized. We
      reviewed the clinical, radiographic and laboratory findings, diagnostic methods,
      therapeutic approaches, and outcome in the patients. Criteria for the diagnosis
      of pancreatic tuberculosis were the presence of granuloma in histological
      sections or the presence of Mycobacterium tuberculosis DNA by polymerase chain
      reaction (PCR). RESULTS: Predominant symptoms consisted of abdominal nodule and
      pain (75 %), anorexia/weight loss (69 %), malaise/weakness (64 %), fever and
      night sweats (50 %), back pain (38 %) and jaundice (31 %). Swelling of the head
      of the pancreas with heterogeneous attenuation echo was detected with ultrasound
      in 75 % (12/16). CT scan showed pancreatic mass with heterogeneous hypodensity
      focus in all patients, with calcification in 56 % (9/16) patients, and
      peripancreatic nodules in 38 % (6/16) patients. Anemia and lymphocytopenia were
      seen in 50 % (8/16) patients, and pancytopenia occurred in 13 % (2/16) patients.
      Hypertransaminasemia, elevated alkaline phosphatase (AP) and GGT were seen in 56
      % (9/16) patients. The erythrocyte sedimentation rate (ESR) was elevated in 69 %
      (11/16) cases. Granulomas were found in 75 % (12/16) cases, and in 38 % (6/16)
      cases caseous necrosis tissue was found. Laparotomy was performed in 75 % (12/16)
      cases, and ultrasound-guided fine needle aspiration (FNA) was done in 63 % (10 of
      16). The most commonly used combinations of medications were
      isoniazid/rifampin/streptomycin (63 %, n=10) and isoniazid/rifampin
      pyrazinamide/streptomycin or ethambutol (38 %, n=6). The duration of treatment
      lasted for half or one year and treatment was successful in all cases. The
      characteristics of 58 cases from Chinese literature were also summarized.
      CONCLUSION: Tuberculosis of the pancreas and peripancreatic lymph nodes should be
      considered as a diagnostic possibility in patients presenting with a pancreatic
      mass, and diagnosis without laparotomy is possible if only doctors are aware of
      its clinical features and investigate it with appropriate modalities. Pancreatic
      tuberculosis can be effectively cured by antituberculous drugs.

PMID- 12800258
TI  - Prevalence of anti-ulcer drug use in a Chinese cohort.
AB  - AIM: To estimate the age-specific prevalence of anti-ulcer drug use and to
      calculate the usage of different anti-ulcer drugs over 5 years within the
      universal health insurance program in Taiwan area. METHODS: The National Health
      Insurance Research Database in Taipei supplied the cohort data sets of 200 000
      people. The ambulatory and inpatient claims of the cohort from 1997 to 2001 were
      analyzed. The anti-ulcer drugs included all drug items of the group A02B (drugs
      for treatment of peptic ulcer) in the Anatomical Therapeutic Chemical
      classification system (version 2000). The amount of drug usage was measured in
      unit of defined daily dose. RESULTS: Among the totally 13 034 393 visits with 56
      672 631 ambulatory prescription items, there were 398 150 (0.7 %) prescribed
      items of anti-ulcer drugs in 378 855 (2.9 %) visits. Among the 107 649 admissions
      with 5 762 312 inpatient prescription items, there were 24 598 (0.4 %) prescribed
      items of anti-ulcer drugs in 11 548 (10.7 %) admissions. The annual prevalence of
      anti-ulcer drug use was 9.6 % in 1997, 11.6 % in 1998, 15.4 % in 1999, 14.5 % in
      2000, and 15.9 % in 2001 respectively. The 5-year prevalence was 36.1 %. The age
      specific prevalence among the people younger than 20 years was 9.2 % in 2001 and
      23.7 % during the 5-year period. Cimetidine not only was the most popular
      ingredient among anti-ulcer drugs (57 634 cimetidine users in 70 729 all anti
      ulcer drug users during the 5-year period) but also had the largest prescribed
      amount (42.3 % of DDDs for all anti-ulcer drug users during the 5-year period).
      The annually prescribed amount of anti-ulcer drugs had grown from 4.9 DDDs/1000
      inhabitants/day in 1997 to 7.5 in 2001. This increase was largely attributed to
      H2-receptor antagonists and the expanding number of users. CONCLUSION:
      Prescribing of anti-ulcer drugs is indeed popular among the Chinese population in
      Taiwan area. The disproportionate use of anti-ulcer drugs by children demands
      further investigation.

PMID- 12800259
TI  - In situ expression and significance of B7 costimulatory molecules within tissues
      of human gastric carcinoma.
AB  - AIM: To explore the role and significance of costimulatory molecules B7H1,B7H2
      and ICOS within tissues of human gastric carcinoma and the possible mechanisms in
      tumor escape. METHODS: mRNA expressions of costimulatory molecules including
      B7H1,B7H2,ICOS and B7-1 in tissues of human gastric carcinoma were investigated
      by in situ hybridization using digoxigenin-labeled oligonucleotide-probes. The
      tissue of chronic gastric ulcer was used as a control. All data were analyzed by
      SPSS statistic software. RESULTS: At the site of gastric carcinoma, mRNA
      expression levels of B7H1, B7H2 and ICOS were much higher than that of B7-1.
      Their mRNA positive expression indexes were 0.512+/-0.333, 0.812+/-0.454, 0.702+/
      0.359 and 0.293+/-0.253, respectively. The positively stained cells were mainly
      tumor infiltrating lymphocytes (TILs), and some tumor cells. The difference
      between them was greatly significant P<0.005. The mRNA expression levels of four
      molecules were not correlated to the pathological grade and matastasis of gastric
      carcinoma. CONCLUSION: ICOS-B7H costimulatory pathway may be predominant at the
      site of gastric carcinoma. B7-1mRNA might be the basis of ICOS-B7H interaction.
      ICOS-B7H interaction induces the production of IL-10 which inhibits the antitumor
      immune responses. Therefore, it is supposed that ICOS-B7H costimulatory pathway
      may be involved in the negative regulation of cell-mediated immune responses.

PMID- 12800260
TI  - Late course accelerated hyperfractionated radiotherapy for clinical T1-2
      esophageal carcinoma.
AB  - AIM: This retrospective study was designed to analyze the results and the failure
      patterns of late course accelerated hyperfractionated radiotherapy for clinical
      T(1-2)N(0)M(0) esophageal carcinoma. METHODS: From Aug. 1994 to Feb. 2001, 56
      patients with clinical T(1-2) esophageal carcinoma received late course
      accelerated hyperfractionated radiotherapy in Cancer Hospital, Fudan University.
      All patients had been histologically proven to have squamous cell carcinoma (SCC)
      and were diagnosed to be T(1-2)N(0)M(0) by CT scan. All patients were treated
      with conventional fractionation (CF) irradiation during the first two-thirds
      course of the treatment to a dose of about 41.4Gy/23fx/4 to 5 weeks, Which was
      then followed by accelerated hyperfractionation irradiation using reduced fields,
      twice daily at 1.5Gy per fraction, to a dose about 27Gy/18 fx. Thus the total
      dose was 67-70Gy/40-43fx/40-49 d. RESULTS: The 1-, 3- and 5-year overall survival
      was 90.9 %, 54.6 %, 47.8 % respectively. The 1-, 3- and 5-year local control rate
      was 90.9 %, 84.5 % and 84.5 %, respectively. Twenty-five percent (14/56) patients
      had distant metastasis and/or lymph nodes metastasis alone. Eight point nine
      percent (5/56) patients had local disease alone. Another 3.6 % (2/56) patients
      had regional relapse and distant metastasis. CONCLUSION: Late course accelerated
      hyperfractionated radiotherapy is effective on clinical T(1-2) esophageal
      carcinoma. The main failure pattern is distant metastasis.

PMID- 12800261
TI  - Multiple immune disorders in unrecognized celiac disease: a case report.
AB  - We reported a female patient with unrecognized celiac disease and multiple extra
      intestinal manifestations, mainly related to a deranged immune function,
      including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti
      b2-glicoprotein-1 antibodies, that disappeared or improved after the
      implementation of a gluten-free diet.

PMID- 12800262
TI  - Hepato-splenic lymphoma: a rare entity mimicking acute hepatitis: a case report.
AB  - We reported a case of non-Hodgkin's lymphoma where liver involvement was the
      predominant clinical manifestation. A 27-year old man presented with markedly
      elevated serum aspartate aminotrasferase, alanine aminotransferase and lactate
      dehydrogenase, reduced prothrombin activity, thrombocytopenic purpura and hepato
      splenomegaly without adenopathy. Viral, toxic, autoimmune and metabolic liver
      diseases were excluded. Bone marrow biopsy showed an intracapillary infiltration
      of T-lymphocytes with no evidence of lipid storage disease. Because of a
      progressive spleen enlargement, splenectomy was performed. Histological
      examination showed lymphomatous intrasinuses invasion of the spleen.
      Immunohistochemical investigation revealed the T phenotype of the neoplastic
      cells: CD45+, CD45RO+, CD3+, CD4-, CD8-, TIA1-. About 50 % of the lymphoid cells
      expressed CD56 antigen. The diagnosis of hepatosplenic T cell lymphoma was done.
      The patient was treated with chemotherapy, which induced a complete remission.
      Eighteen months later, he had a first relapse with increased aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase,
      thrombocytopenic purpura and blast in the peripheral blood. In spite of
      autologous bone marrow transplantation, he died twenty months after the
      diagnosis. Even in the absence of a mass lesion or lymphoadenopathy,
      hepatosplenic T-cell lymphoma should be considered in the differential diagnosis
      of a patient whose clinical course is atypical for acute hepatic dysfunction.

PMID- 12800263
TI  - The effect of an additional flowable compomer layer on microleakage of Class V
      compomer restorations.
AB  - BACKGROUND: Polymerisation shrinkage and the associated stress on composite
      resins and surrounding structures have been regarded as a major cause of leakage
      and clinical failures in modern polymer restorations. The purpose of this study
      was to investigate the effect of an additional flowable compomer layer on the
      microleakage of Class V dental cavities, which were further filled with a
      compomer. METHOD: Cavities (32) were prepared in human premolars, conditioned
      with a non-rinsing agent (Prime & Bond NRC) and treated with the bonding agent
      (Prime & Bond NT). Sixteen of these cavities were then lined with a layer of
      flowable compomer (Dyract Flow, approximately 0.5 mm) and further filled with
      Dyract AP. The other 16 cavities were filled without the flowable compomer. The
      specimens were thermo-cycled in a 0.5% basic fuchsin solution, sectioned and
      evaluated for dye penetration using a scoring system of 0 to 4. RESULTS: Lower
      microleakage values were found at the enamel as well as at the dentine sides when
      a layer of Dyract Flow was used as a liner. Furthermore, significantly (p < 0.05)
      lower microleakage was found in enamel than in dentine for both layered and
      unlayered restorations. CONCLUSION: It can be concluded that a layer of flowable
      compomer (i.e. Dyract Flow) in a cavity under a compomer may be recommended to
      improve the marginal seal of a restoration.

PMID- 12800264
TI  - Circular from a certain managed healthcare company.

PMID- 12800265
TI  - How well do fourth year Wits dental students place resin composite restorations?
AB  - OBJECTIVES: To evaluate, by means of a scanning electron microscope (SEM) the
      quality of resin composite restorations, placed as a first attempt by fourth-year
      dental students. METHODS: Ten Class IV direct composite restorations, placed in
      plaster-mounted extracted incisor teeth as part of pre-clinical course
      requirements, were selected. Specimens were evaluated and graded on a two-point
      scale by a staff member according to departmental clinical evaluation criteria.
      Five restored teeth were prepared for surface evaluation of marginal integrity,
      surface roughness and contour using SEM. The remaining specimens were embedded in
      resin and ground down transversely, parallel to the incisal edge until a dentine
      core was apparent. The ground surfaces were polished, prepared for SEM and
      assessed for etched layer, placement of bonding agent, composite adaptation and
      overall consistency. RESULTS: Clinical assessment and SEM surface evaluation
      correlated favourably for all criteria, except contour, indicating that students
      were reasonably competent in finishing techniques. Ground samples revealed
      acceptable etched enamel layers and marginal adaptation. Bonding agent thickness
      varied between 0 and 200 microns casting doubt on procedural accuracy. Porosities
      and voids were apparent within the resin composite. Internal features were the
      main reason for unsatisfactory grades. CONCLUSIONS: Students placed restoration
      satisfactorily. They would benefit if able to examine sectioned restorations to
      understand critical placement techniques which would contribute to resin
      composite restoration success. A research component can be introduced into the
      dental undergraduate curriculum by way of similar projects linked to didactic
      course-work.

PMID- 12800266
TI  - Auriculo-temporal nerve. Clinicopathological relevance to facial-maxillary
      practice.
AB  - Anatomically, the auriculo-temporal nerve (ATN), a peripheral branch of the
      trigeminal nerve is in close relation to the parotid gland, neck of the mandible,
      temporal vessels, and sphenomandibular ligament. Fine branches of the ATN are at
      risk of division during surgical intervention of the parotid gland or condyle of
      the mandible. "Frey's syndrome", or abnormal gustatory sweating, may be a
      consequence of injury to the branches of the auriculo-temporal nerve. This
      uncommon syndrome can also occur with fractures of the temporo-mandibular joint
      (TMJ), due to the anatomic proximity of the nerve to the bone.

PMID- 12800267
TI  - Prosthodontic treatment of the edentulous adult cleft palate patient.
AB  - Clefts of the upper lip and plate are relatively common, yet dental treatment of
      these patients is still very poor and many grow up suffering dental neglect.
      Dental practitioners should become involved in the treatment team as dental needs
      are present from birth to death. Adult cleft patients often need tooth
      replacement with obturation of any residual clefts. They are best treated with
      tooth-supported removable appliances including partial and complete overdentures,
      thus preservation of their natural dentition is desirable. Edentulous cleft
      palate patients present with restorative difficulties due to their compromised
      maxillary arches as well as the presence of scar tissue in their palates and
      lips. An outline of these complications and guidelines for their treatment is
      illustrated in the form of three case reports from members of one family all
      presenting with varying cleft lip and palate defects. This article highlights the
      need for dental students to be exposed to dentally compromised patients so that
      they will feel confident enough to treat them in private practice.

PMID- 12800268
TI  - Management of microleakage in dental compomers.

PMID- 12800269
TI  - The reduction of postoperative pain after amalgam fillings.

PMID- 12800270
TI  - How sure are we that HIV causes AIDS?

PMID- 12800271
TI  - Oral mucosal lesions caused by Candida albicans.

PMID- 12800272
TI  - A primer on digital X-ray imaging for dentistry.

PMID- 12800273
TI  - States suspend vaccinations in wake of deaths.

PMID- 12800274
TI  - Where desert storms.

PMID- 12800275
TI  - The healer and her art.

PMID- 12800276
TI  - Is now the time?

PMID- 12800277
TI  - An investigation into the level and impact of merger activity amongst hospitals
      in the UK's National Health Service.
AB  - Since 1990 the National Health Service (NHS) has undergone a sustained period of
      change. This change has been necessary to prepare the NHS for the task of meeting
      a demand for services that continues to rise more rapidly than the availability
      of resources. Anecdotal evidence suggests that one of the most popular ways for
      trusts to improve their ability to meet demand is through mergers with other
      trusts. However, little rigorous research has been conducted to assess the extent
      or effectiveness of this strategy. A research project was, therefore, initiated
      to better understand the extent and impact of merger activity within the NHS. A
      questionnaire was developed and distributed to the chief executive, finance
      director, medical director and human resources director in all the 460 trusts
      that are currently members of the NHS confederation. In total the survey
      generated 459 responses out of a possible total of 1,840; an encouraging response
      rate of 25 per cent. The results of this research provide significant new
      evidence that "merger mania" has taken hold within the NHS. While 46 per cent of
      all responding trusts indicated that they had already merged, are actively
      involved in a merger, proposing to merge or are talking to prospective partners,
      a further 18.7 per cent of all trusts are forming strategic alliances rather than
      opting for a full merger. The dominant justification for merging are the beliefs
      that it will facilitate the reconfiguration of services and ultimately improve
      patient care. The paper concludes with a discussion of the significance of these
      results, before making recommendations with regard to their implications for
      future merger activity within the NHS.

PMID- 12800278
TI  - How are Scottish integrated primary care organisations managed?
AB  - In the absence of central guidance on the development of integrated primary care
      organisations, a diversity of models is emerging. This paper examines the
      management arrangements of Scottish local health care co-operatives (LHCCs). A
      postal questionnaire survey of all 79 LHCCs was conducted. The response rate was
      35 per cent. LHCCs set up management bodies and created workgroups. Stakeholder
      representation was not socially inclusive: attempts to engage patients and local
      communities were limited and need to be stepped up to increase responsiveness and
      accountability to local health care users. LHCCs were also vehicles for local
      ownership and control of health care provision. To facilitate co-operation among
      participating practices, LHCCs need to focus on issues of leadership,
      organisation, and involvement in decision making. Finally, management expenditure
      per capita was comparable with that of other types of integrated primary care
      organisations.

PMID- 12800279
TI  - Delphi: myths and reality.
AB  - The last 20 years have seen increasing interest in the use of Delphi in a wide
      range of health-care applications. However, this use has been accompanied by
      attempts to codify and define a "true Delphi". Many authors take a narrow view of
      the purpose of Delphi and/or advocate a single prescriptive approach to the
      conduct of a Delphi study. However, as early as 1975, Linstone and Turoff pointed
      to the danger of attempting to define Delphi as one would immediately encounter a
      study that violated that definition. Through critical examination of some of the
      controversies and misunderstandings that surround Delphi, this paper aims to
      dispel some of the myths and demonstrates the wide scope and potential of this
      versatile approach.

PMID- 12800280
TI  - Part-time work and job sharing in health care: is the NHS a family-friendly
      employer?
AB  - This paper examines the nature and level of flexible employment in the National
      Health Service (NHS) by investigating the extent to which part-time work and job
      sharing arrangements are used in the provision and delivery of health care. It
      attempts to analyse the reasons for an increasing number of part-timers and a
      very limited number of job sharers in the NHS and to explain the advantages and
      disadvantages of each pattern of employment. Data collected through the use of
      questionnaires and interviews from 55 NHS trusts reveal that the use of part-time
      work is a tradition that seems to fit well with the cost-saving measures imposed
      on the management of the service but at the same time it has led to increasing
      employee dissatisfaction, and that job sharing arrangements are suitable for many
      NHS employees since the majority of them are women with a desire to combine
      family commitments with career prospects but a very limited number of employees
      have had the opportunity to job share. Therefore it is concluded that to attract
      and retain the quality of staff needed to ensure high performance standards in
      the provision and delivery of health care the NHS should accept the diversity
      that exists within its workforce and take a more proactive approach to promoting
      a variety of flexible working practices and family-friendly policies.

PMID- 12800281
TI  - Hospitals play hardball. DMC, others are telling governments they can choose
      between giving them more money or accepting cutbacks.
AB  - Hospitals are applying the same gritty, hard-nosed negotiating tactics they used
      with commercial payers to a new target: local government. For example, Detroit
      Medical Center has announced major cuts unless city, county and state governments
      pledge to boost funding. DMC Chairman Dick Gabrys, left, says the system means
      business.

PMID- 12800282
TI  - Maine's right prescription. Justices approve controversial drug-pricing law.

PMID- 12800283
TI  - Universal solution. Maine governor offers plan to cover everyone.

PMID- 12800284
TI  - Writing on the wall. Congressional panel says Health South's fraud warnings date
      back to '98.

PMID- 12800285
TI  - Cracking down on GPOs. Proposed California law would put limits on business
      practices.

PMID- 12800286
TI  - No more Minnesota nice. Medica seeks to revoke state attorney general's board
      oversight.

PMID- 12800287
TI  - Changing the rules. La. bill would cut oversight of public hospitals.

PMID- 12800288
TI  - The new prevention. Research on causes of disease must be applied to remaking our
      care system.

PMID- 12800289
TI  - Not just a Web site. In response to consumers as well as competitors, hospitals
      are getting more sophisticated with their Internet presence.

PMID- 12800290
TI  - Always vigilant. At Banner Health in Phoenix, a computerized decision-support
      system helps warn caregivers when adverse drug interactions or other harmful
      events are imminent.

PMID- 12800291
TI  - Straight talk. New approaches in healthcare. Hospital/physician partnerships are
      key to growth of market share.
AB  - Do you know who your biggest competitor is? It's probably your most loyal
      physician group. That's because up to 80% of hospitals are competing with their
      own medical staffs, according to PricewaterhouseCoopers' research. Physicians are
      launching revenue enhancement and diversification strategies to combat declining
      reimbursement and respond to the surge in demand for outpatient services. THE
      SOLUTION: Hospital administrators need to aggressively develop economic
      partnerships with their medical staff. In this installment of Straight Talk, we
      discuss how two institutions have crafted viable hospital and physician ventures.
      Modern Healthcare and PricewaterhouseCoopers present Straight Talk. The session
      on growth strategies was held on May 6, 2003. Charles S. Lauer, publisher of
      Modern Healthcare, was the moderator.

PMID- 12800292
TI  - [Stronger professional role of the nurse: from doctor's aide to an equal
      partner].

PMID- 12800293
TI  - [The Melanoma Monday saves life and money. Four findings of malignant melanoma
      among 161 examined persons].

PMID- 12800294
TI  - [Humanized antibodies against an adhesion molecule block the CNS inflammation in
      multiple sclerosis].

PMID- 12800295
TI  - [Tinnitus affects 15 percent--today's environmental noise a risk factor. Early
      treatment can prevent chronic problems].
AB  - A substantial proportion of individuals in the general population have tinnitus
      and 1-3% suffer from severe tinnitus affecting sleep, concentration, and mood.
      For a majority of patients with tinnitus degree of hearing loss plays a
      significant role. Several potential causes and aggravating factors have been
      suggested, but there is still not a single theory available to explain why
      tinnitus is so bothersome for some individuals. Recent research has investigated
      neural correlates of tinnitus, mainly involving primary and secondary auditory
      cortex. Several treatments have been tested with modest results. However, for the
      alleviation of tinnitus-related distress there is now empirical support for the
      use of cognitive-behavioural treatment methods. Future efforts should focus on
      prevention of noise-induced hearing loss and ways to foster habituation to
      tinnitus.

PMID- 12800297
TI  - [After the record hot summer of 2002... Mechanisms behind the heat stroke are
      more clear].

PMID- 12800296
TI  - [Radical prostatectomy reduces the risk of death in prostatic cancer. The effect
      on total mortality can not be established yet as shown in a randomized controlled
      trial].

PMID- 12800298
TI  - [Homocysteine and cardiovascular disease--still no evidence for a connection. An
      unknown risk factor can be involved according to a systemic review].

PMID- 12800299
TI  - [Poisoning by ethylene glycol in windshield washer fluid. Two persons nearly died
      because of a new product with a new formula].

PMID- 12800300
TI  - [The law concerning biobanks is a strain on health care work].

PMID- 12800301
TI  - [Why does the SaluAnsvar avoid scrutiny?].

PMID- 12800302
TI  - [Does lead cause renal damage? Surprising results published in a respected
      journal].

PMID- 12800303
TI  - [The role of geriatrics in Swedish health services for the aged must become
      stronger].

PMID- 12800304
TI  - [Non-pasteurized beverages not always as beneficial as promised by the product
      information].

PMID- 12800305
TI  - [A written examination for interns should not only consist of easy questions on
      common conditions!].

PMID- 12800306
TI  - [Increased GT level without known cause created problems for the patient].

PMID- 12800307
TI  - Public sector retirement systems: what does the future hold?
AB  - Public pension plans will continue to search for cost-sharing retiree health care
      solutions and may shift to a defined contribution emphasis. Fiduciary
      responsibility will be highlighted in view of controversial plan changes,
      government budgetary constraints, scrutinized investment return assumptions,
      potential labor shortages and increased shareholder activism.

PMID- 12800308
TI  - The changing world of ancillary benefits.
AB  - Amid salary and health care benefit cuts, ancillary benefits such as dental, life
      insurance, long-term disability and vision coverage can communicate employers'
      concern for their employees as well as serve as recruitment and retention tools.
      These benefits can be funded by the employer, the employee or both.

PMID- 12800309
TI  - A review of dental plans: PPOs and referral plans to dominate future.
AB  - This important benefit has changed greatly in the last 20 years. Double-digit
      health care cost increases in the late 1980s caused indemnity plans to evolve
      into network plans, such as dental HMOs and PPOs. PPOs and referral or access
      plans now seem to be the plans of choice.

PMID- 12800310
TI  - Health plan diagnostics: what plan sponsors and trustees need to know.
AB  - The needed information for diagnosing the cost-effectiveness of the health plan
      includes understanding where cost pressures are coming from, how the plan
      compares to other plans and the key characteristics of the covered group.
      Allocating resources for the staff or consultants to produce and analyze this
      information is a wise investment. Two case studies illustrate the power of plan
      diagnostics to lead to positive solutions that address cost increases--without
      hurting plan members.

PMID- 12800311
TI  - Converting unused vacation days to retiree medical benefits: a proposed partial
      solution to an emerging national crisis.
AB  - Costs for retiree medical benefits are spiraling upward. One way to help fund
      this area of compensation, with little or no additional financial burden to
      either employers or employees, could be using an employee benefit plan whereby
      each year's unused vacation days and sick days are transferred into an employee's
      tax-free account in a voluntary employee benefit association (VEBA) trust. On
      retirement, the account is used to purchase a (pre-Medicare) retiree medical
      plan, prescription drug benefit, a Medicare supplemental policy and/or simply
      make Medicare premium payments.

PMID- 12800312
TI  - Using a 401(h) account to fund retiree health benefits from your pension plan.
AB  - If a health and welfare plan covering retirees faces financial shortfalls,
      administrators and trustees can fund retiree health benefit payments from a
      related pension plan that may be in better condition. This method is legal and
      ethical, but it requires sophisticated accounting techniques for creating an
      account that provides retiree members with promised benefits while meeting
      statutory and regulatory requirements.

PMID- 12800313
TI  - The killer strain.

PMID- 12800314
TI  - Parents in a haze.

PMID- 12800315
TI  - A battle over the morning-after pill.

PMID- 12800316
TI  - What makes you who you are.

PMID- 12800317
TI  - Breaking bread.

PMID- 12800318
TI  - The first modern plague: epidemic encephalitis in America, 1919-39.

PMID- 12800319
TI  - The strange case of Silas W. Mitchell: writing and injury in the Gilded Age.

PMID- 12800320
TI  - The papers of Edward O. Shakespeare.

PMID- 12800321
TI  - Anthropodermic book-bindings.

PMID- 12800322
TI  - Howard A. Kelly's development as an academician: some insights from his letters
      to Robert P. Harris.
AB  - Howard Atwood Kelly (1858-1943), Professor and Gynecologist in Chief at the Johns
      Hopkins School of Medicine, is widely known as an innovator in operative
      gynecology, urology, and abdominal surgery. He was also a first-rate naturalist
      and bibliographer. Less is known, however, about his formative years as a young
      surgeon in Philadelphia. During a four-month period, from May to September 1886,
      while on a trip to Europe, Kelly wrote his senior colleague and friend Robert
      Patterson Harris (1822-1899) almost three dozen letters. These letters trace the
      development of Kelly's ideas as he visited a number of medical luminaries in the
      major medical centers of Germany, England, Scotland, and France. Overall, the
      letters give considerable insight into the development of Kelly as a young
      physician (age 28), inspired by what he saw in the German Frauenkliniks to build
      a program of excellence in the treatment of diseases of women in America. In
      addition, the letters help to illustrate the role Harris played in the
      development of this icon of contemporary medicine, who, with others, worked to
      place the Johns Hopkins School of Medicine at the forefront of medical education
      and research in this country and the world.

PMID- 12800323
TI  - A temperate history of emergency care: from a necessary evil to a community
      obligation.

PMID- 12800325
TI  - Essay reviews.

PMID- 12800324
TI  - A twenty-first century perspective on the ancient art of bloodletting.

PMID- 12800326
TI  - Cures on the cob.

PMID- 12800327
TI  - Blood pressure high? A new definition of normal makes 45 million Americans
      "prehypertensive".

PMID- 12800328
TI  - The plague busters. Stopping a new and deadly mix of syphilis and HIV.

PMID- 12800329
TI  - Her own STD barrier.

PMID- 12800330
TI  - One cheer for Atkins.

PMID- 12800331
TI  - Risky business. Big insurers rig the game to avoid covering people likely to file
      claims.

PMID- 12800332
TI  - Depression. Coping with a spouse's death.

PMID- 12800333
TI  - The health insurance blues. Medicare doesn't cover spouses, or costly drugs, so
      some put off retiring.

PMID- 12800334
TI  - Baby steps. Has a century of child-rearing advice taught us anything?

PMID- 12800335
TI  - Do-it-yourself diagnosis.

PMID- 12800336
TI  - Testing made easy.

PMID- 12800337
TI  - Tyranny of the 'or'.

PMID- 12800338
TI  - PD: a biological membrane and a non-biological fluid.

PMID- 12800339
TI  - Ecology of the peritoneum: a substantial role for the osmotic agents resulting in
      apoptosis of mesothelial cells.

PMID- 12800340
TI  - Different aspects of peritoneal sclerosis.

PMID- 12800341
TI  - Biological markers in peritoneal effluent: are they useful?

PMID- 12800342
TI  - GDPs and AGEs: local and systemic effects in PD patients.

PMID- 12800343
TI  - Long-term results with low glucose degradation product content in peritoneal
      dialysis fluids.

PMID- 12800344
TI  - Peritoneal microcirculation.

PMID- 12800345
TI  - Clinical effects of bicarbonate-based peritoneal fluid.

PMID- 12800346
TI  - Ten years after MIDAS: icodextrin lights and shadows.

PMID- 12800348
TI  - Obesity on PD patients: causes and management.

PMID- 12800347
TI  - Cardiovascular risk in peritoneal dialysis.
AB  - All patients with CKD have multiple risk factors for CVD and CAD in particular.
      Some of these risk factors such as age and gender cannot be modified. Others such
      as diabetes and hypertension are not only CVD risk factors but are also the cause
      of the patient's CKD. Finally there are a group of risk factors such as
      disturbances of mineral metabolism and oxidative stress which are present either
      uniquely in or are exaggerated by renal failure. PD gives patients a more
      atherogenic lipid and lipoprotein profile, puts them at greater risk for AGE
      formation and usually causes hyperinsulinemia. All of these contribute to CVD
      risk. However, they can also achieve excellent blood pressure control, usually
      easily reach targets for anemia management and have continuous ultrafiltration
      allowing for the maintenance of good volume status, all of which will reduce risk
      for CVD. All treatable risk factors should be treated early in the development of
      CKD and should continue through their time on dialysis and after transplantation.

PMID- 12800349
TI  - Assessment of comorbidity in peritoneal dialysis patients.

PMID- 12800350
TI  - Chronic inflammation in PD patients.

PMID- 12800351
TI  - Malnutrition in peritoneal dialysis patients: causes and diagnosis.

PMID- 12800352
TI  - Can the vicious inflammation-malnutrition circle be corrected?

PMID- 12800353
TI  - Implications of the ADEMEX trial.

PMID- 12800355
TI  - Recent K/DOQI guidelines: applications in peritoneal dialysis patients.

PMID- 12800354
TI  - Evaluation of guidelines for peritoneal dialysis patients: a review from the
      Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD).

PMID- 12800356
TI  - Clinical Practice Guidelines of the Canadian Society of Nephrology for the
      treatment of patients with chronic renal failure: a re-examination.

PMID- 12800357
TI  - European best practice guidelines: adequacy in peritoneal dialysis.

PMID- 12800358
TI  - When to start dialysis: theory, evidence and guidelines.

PMID- 12800359
TI  - Treatment of infections in peritoneal dialysis.

PMID- 12800360
TI  - Peritoneal access.

PMID- 12800361
TI  - Evidence-based medicine in peritoneal dialysis: peritoneal dialysis solutions.

PMID- 12800362
TI  - Integration of peritoneal dialysis and adequacy beyond Kt/V.

PMID- 12800363
TI  - Peritoneal dialysis as the first-choice treatment.

PMID- 12800364
TI  - Impact of peritoneal dialysis on patient and graft outcome after kidney
      transplantation.

PMID- 12800365
TI  - Renal transplantation and peritoneal dialysis.

PMID- 12800366
TI  - Is PD a suitable treatment after an unsuccessful transplant?

PMID- 12800367
TI  - Clinical management of the PD patient after transplantation.

PMID- 12800368
TI  - What is the role of automated peritoneal dialysis and continuous flow peritoneal
      dialysis?

PMID- 12800369
TI  - APD schedules and clinical results.

PMID- 12800370
TI  - Automated peritoneal dialysis technology.

PMID- 12800371
TI  - Continuous flow peritoneal dialysis: current perspectives.

PMID- 12800372
TI  - Potential for sorbents in continuous flow peritoneal dialysis.

PMID- 12800373
TI  - Solution formulation for continuous flow peritoneal dialysis.

PMID- 12800374
TI  - A 2-year-old girl with failure to thrive, progressive hepatosplenomegaly and
      progressive encephalopathy.

PMID- 12800375
TI  - Polyostotic Langerhans cell histiocytosis and El Nino: a novel hypothesis.

PMID- 12800376
TI  - Isolated complete agenesis of corpus callosum.
AB  - Agenesis of corpus callosum (ACC) often accompanies other neural migration
      disorders and its prognosis must take these disorders and other associated
      abnormalities into account. Isolated complete ACC, i.e., agenesis of corpus
      callosum without other central nervous system anomaly, is rare. A total of six
      patients, aged nine months to 15 years, with isolated complete ACC diagnosed by
      brain image study in the past eight years of our hospital were evaluated for
      associated defects and prognosis. Isolated complete ACC without associated
      congenital heart disease (CHD) was found in four of the six patients (4/6), of
      whom three had normal development so far. The other two patients (2/6) were found
      to have associated CHD and both had poor prognosis. This result suggests that
      checking for any associated CHD may play an important prognostic role for
      isolated complete ACC patients. Therefore, it is recommendable that prenatal
      brain MRI and fetal echocardiography should be performed for evaluation and for
      genetic consultation whenever ACC is suspected.

PMID- 12800377
TI  - Hepatic hemangioendothelioma in children: analysis of thirteen cases.
AB  - Hepatic hemangioendothelioma (HE) is a tumor that presents in infancy and
      toddler. It manifests hepatomegaly, abdominal mass, jaundice, abdominal
      distention, or high output cardiac failure. We reviewed patients with HE in our
      hospital in the past 15 years (from July 1986 to June 2001). The diagnosis was
      made by the histology specimen or various imaging studies. There were thirteen
      patients (9 males, 4 females) enrolled in our study. Their ages ranged from
      neonate to 2 years old. The common clinical manifestations included abdominal
      distention (53%), congestive heart failure (38.5%), abdominal mass (30.8%),
      jaundice (30.8%), and skin hemangioma (23.1%). Nine patients had serum alanine
      aminotransferase examination and were abnormal in 2. Anemia was noted in 7 of 13
      (53.8%) patients, thrombocytopenia and hyperconsumptive coagulopathy were found
      in 4 and 5 patients, respectively. Serum alpha-fetoprotein was elevated in 4 of 7
      patients. Abdominal ultrasonography (n = 13) showed heterogeneous and hypoechoic
      lesions in the liver. Computed tomography (n = 11) revealed central hypointensity
      with peripheral enhancement after contrast of the liver masses. Magnetic
      resonance imaging studies of the hepatic masses (n = 3) showed decreased signal
      intensity on T1 images and high signal intensity on T2. Most patients were
      treated with steroid. Other management included interferon, chemotherapy,
      embolization and/or surgery. Four patients were managed conservatively. Among the
      other nine patients, four patients died of sepsis, hepatic failure, disseminated
      intravascular coagulopathy or tumor rupture with hemorrhagic shock. HE appears to
      be a histologically benign tumor but may have a poor outcome because of
      complications. For its management, steroid is a first-line medication. Other
      methods of treatment were interferon, hepatic artery embolization, chemotherapy
      and surgery. Long term follow up is needed for the evaluation of treatment
      response.

PMID- 12800378
TI  - Childhood Langerhans cell histiocytosis increased during El Nino 1997-98: a
      report from the Taiwan Pediatric Oncology Group.
AB  - From 1995-1999, a nation-wide study of Langerhans cell histiocytosis (LCH) in
      children less than 15 years old was conducted by the Taiwan Pediatric Oncology
      Group. The demographic and clinical data of 55 cases were analyzed. Thirty-two
      cases presented from the beginning of 1997 to the end of 1998, when the most
      severe El Nino in the century occurred. The incidence was higher than expected
      during this El Nino period (32 cases versus 22 cases, p = 0.003). During 1997-98,
      most LCH was diagnosed in summer (n = 15), autumn (n = 8), and winter (n = 8) but
      rarely in spring (n = 1); coincidentally, rainfall was least in winter but peaked
      in summer. During 1997-98, the most significant increase occurred in the
      polyostotic LCH subcategory (p = 0.017), with younger ages at diagnosis (p =
      0.039). The incidence of LCH cytopenia, fever, and diseases of the skin, liver,
      spleen or other organs did not differ significantly. Local treatment modality,
      disseminated diseases and diagnosis during the El Nino of 1997-98 were
      independent risk factors predicting the recurrence or progression of LCH. Our
      findings suggest that particular infections or other environmental factors
      associated with El Nino might be related to the etiology of childhood LCH.

PMID- 12800379
TI  - Auditory brainstem response in children with iron deficiency anemia.
AB  - To investigate the neurosensorial influences with auditory brainstem response
      (ABR) in iron deficiency anemia. We recorded ABR in 33 children with iron
      deficiency anemia followed and in 31 healthy children (control group 1, 0-12
      months, control group 2, 13-36 months, control group 3, 37-60 months) as a
      control group. The patients and controls were divided into three group: group I,
      at 12 months of age, group II, 13-36 months, and group III, 37-60 months. In all
      groups, composed latency time, inter-peak latency, amplitude of peaks, I-V wave
      amplitude ratio and waveform were evaluated and compared with control groups. In
      group I, I-V interpeak latency was increased compared with control group I (4.58
      vs. 4.20 ms, p < 0.05). In group II, Wave V latency time and III-V interpeak
      latency were increased compared with control group 2 (6.21 ms vs. 5.63 ms. p <
      0.005 and 0, 48 vs. 0.22 p < 0.005, respectively). In group III, wave I latency
      time was increased compared with control group 3 (1.56 ms vs. 1.46 ms) (p <
      0.05). We considered that increases in ABR latencies might be explained by
      delayed maturation of myelinisation, which requires iron, and/or by dysfunction
      of iron containing enzymes.

PMID- 12800380
TI  - Neonatal varicella frequently associated with visceral complications: a
      retrospective analysis.
AB  - Neonates are very susceptible to varicella, which usually causes high mortality
      and morbidity rates among that age group. We analyzed the prognosis and
      complications of neonates with varicella in a retrospective study that assessed
      the clinical features, laboratory data, and clinical outcomes of twelve neonates
      who either had the illness or who were at risk. Based on exposure history, twelve
      babies were separated into prenatal and postnatal infection groups. Seven cases
      were categorized as having prenatal infections and five had postnatal varicella
      infection. Results showed that the major complications in the prenatal infection
      group included three cases of hepatitis, two of pneumonia, one of pyoderma and
      one of sepsis. The presence of fever was a good indicator for predicting
      complications among the prenatal infection group. These complications were not
      found in the postnatal infection group. We found that prenatal varicella
      infections appear to have a higher visceral complication rate. However, our
      patients had a much lower mortality rate than those reported in previous studies.
      This may be attributed to the administration of acyclovir after delivery.

PMID- 12800381
TI  - Analysis of factors associated with initiation and duration of breast-feeding: a
      study in Taitung Taiwan.
AB  - Breast-feeding practices were studied in 251 mother-infants pairs at the well
      baby clinic of a regional hospital in Taitung, Taiwan. A questionnaire was
      designed to elucidate factors influencing the initiation and duration of breast
      feeding. Most of the mothers (81.7%) initiated breast-feeding after delivery, but
      only 20.7% continued nursing for at least 4 months. Factors positively associated
      with initiating breast-feeding were the approval of the baby's father and
      grandparents and assistance from healthcare staff. Infants who were hospitalized
      during neonatal period and those born in the largest regional hospital were less
      likely to be nursed. Women who were employed and those with a higher education
      level were less likely to breast-feed > or = 4 months. Among infants > or = 4
      months old at the time of the study, those who were younger were less likely to
      have had at least 4 months of breast-feeding. The father's approval positively
      influenced the duration of breast-feeding. There is still a need for active
      promotion of and support for breast-feeding. Healthcare workers should offer
      assistance, and particular attention should be paid to help families with
      hospitalized newborns. Including fathers and grandparents in discussions about
      breast-feeding is imperative. We must also develop ways to encourage and enable
      employed mothers to continue breast-feeding for longer periods.

PMID- 12800382
TI  - Infantile subglottic hemangioma treated by intralesional steroid injection:
      report of one case.
AB  - Infantile subglottic hemangioma is a rare, life threatening disease of the
      larynx. Various treatments have been described in the literature, including
      tracheostomy, systemic steroids, intralesional steroid injection, carbon dioxide
      laser therapy, and interferon alfa-2a. The best treatment, however, remains
      controversial. We report a case of congenital subglottic hemangioma successfully
      managed with a single intralesional steroid injection, which resulted in rapid
      involution of the hemangioma without recurrence after 18 months of follow up.
      This therapy appears to minimize both short and long term morbidity associated
      with treatment of this lesion.

PMID- 12800383
TI  - Umbilical vein catheter malposition: report of one case.
AB  - A male premature newborn was diagnosed as respiratory distress syndrome shortly
      after birth. Umbilical arterial and venous catheters were inserted. The position
      of the umbilical venous catheter was erroneous roentgenographically, but return
      of blood was noted when the catheter was pull back to below the diaphragm. After
      fluid infusion via the catheter, swelling of buttock, scrotum and bilateral
      thighs with pitting edema over the abdominal wall and lower back, and increased
      body weight were noted the next day. The abdomen was distended without bluish
      discoloration. Laboratory studies showed neither anemia nor hypoalbuminemia.
      Blood pressure was 42/28 mmHg. The abdominal reoentgenogram showed bowel gas
      pattern suggesting the presence of fluid within the peritoneal cavity. The
      catheter of the umbilical vein was removed. Repeat abdominal reoentgenogram the
      following day showed resorption of the fluid. The infant was gavage fed. The
      catheter perforated the umbilical vein and went into the retroperitoneal area.
      This complication is rare. This case is presented with a review of the
      literature, concluding that if there are uncertainties about the location of the
      catheter, verification should include having blood returned from the umbilical
      venous catheter and taking lateral and frontal films before fluid infusion
      starts.

PMID- 12800384
TI  - Laparoscopy diagnosis and treatment excision of bleeding Meckel's diverticulum in
      a child: report of one case.
AB  - Meckel's diverticulum is a common cause of low gastrointestinal bleeding in
      childhood. Conventional diagnostic methods including plain abdominal radiographs,
      abdominal ultrasound, technectium 99m pertechnetate scintigraphy, angiography,
      and exploratory laparotomy have several limitations. Here, we report that a case
      of Meckel's diverticulum in a 1-year-7-month-old boy presenting with intermittent
      episodes of painless low gastrointestinal bleeding for about one year. Despite
      the traditional studies, including plain abdominal films, abdominal ultrasound,
      rectosigmoidoscopy and repeated Tc-99m Meckel's scan, all showed negative
      finding, it was successfully diagnosed along with excision of Meckel's
      diverticulum by laparoscopy. The patient made a rapid recovery and discharged at
      48 hours after the procedure. We emphasize that laparoscopy should be an
      alternative diagnostic and therapeutic modality of choice in patients suspected
      of Meckel's diverticulum, especially in pediatric patients who had negative
      results of all other work-ups.

PMID- 12800385
TI  - Pseudohypoaldosteronism presenting as acute gastroenteritis: report of one case.
AB  - Pseudohypoaldosteronism type I, a disorder of mineralocorticoid resistance,
      usually presents with excessive renal sodium wasting and subsequent poor growth.
      We report a 1-month-old male baby who suffered from recurrent vomiting, diarrhea
      and dehydration. Biochemical investigations showed hyponatremia, hyperkalemia,
      hypochloremia, metabolic acidosis and large amount of urinary sodium excretion.
      Owing to persistent electrolyte abnormalities and renal salt loss, hormone
      studies were done and revealed elevated concentrations of cortisol,
      adrenocorticotropic hormone, aldosterone, renin and 17-hydroxyprogesterone. Blood
      pressure and plasma sugar were normal. The external genitalia were normal without
      hyperpigmentation. The laboratory data coupled with clinical presentations
      suggested pseudohypoaldosteronism type I. Aggressive sodium replacement and fluid
      therapy were started, with good response.

PMID- 12800386
TI  - Duplication of transverse colon: report of one case.
AB  - Alimentary tract duplications are very rare, with a reported incidence of 1 in
      5000 live births. However, it rarely affects the transverse colon. We reported a
      case of duplication of the transverse colon in a 12-year-old boy with an unusual
      presentation mimicking megacolon. Barium enema revealed a large sac with massive
      fecal material retention in the left side of abdomen. Barium filling of the sac
      displacing bowel loops was noted on the post-evacuation film. He received a
      segmental resection of the transverse colon including the duplicated colon and
      end-to-end colo-colostomy. Pathology revealed whole muscle layer of colon
      compatible with duplication. No other associated anomaly was noted in this case.
      The case demonstrates three relatively uncommon presentations, including
      transverse colon location, late manifestation and dilated colon mimicking
      megacolon radiologically. It also emphasizes that barium enema with post
      evacuation film aids in the preoperative diagnosis of duplication.

PMID- 12800387
TI  - Del (9p) syndrome: report of four cases.
AB  - The chromosome 9p deletion [del (9p)] syndrome is a rare but specific clinical
      entity. The clinical manifestations include dysmorphic facial features
      (trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures, and a
      long philtrum) and psychomotor retardation. Four patients with characteristic
      features of del (9p) syndrome were reported. Cytogenetic analysis showed a de
      novo deletion of the short arm of chromosome 9 with the breakpoint being located
      at band 9p22 in all cases. Fluorescence in situ hybridization using painting
      probe for chromosome 9 excluded translocations involving 9p and another
      chromosome. Long-term follow-up in these patients showed that neuro-psychiatric
      problems were common in their later ages.

PMID- 12800388
TI  - Hailing one of health care's priceless resources--nurses.

PMID- 12800389
TI  - Changes that challenge nursing education.

PMID- 12800390
TI  - Tennessee Nurses Association legislative report.

PMID- 12800391
TI  - The innovative nurse: an oxymoron?

PMID- 12800392
TI  - ANA hails Congressional agreement on Nurse Reinvestment Act.

PMID- 12800393
TI  - Proposed bylaws amendments.

PMID- 12800394
TI  - Health policy: a critical call for nursing involvement.

PMID- 12800395
TI  - Tennessee Nurses Association legislative report.

PMID- 12800396
TI  - Safety, efficacy, and cost advantages of combined coronary angiography and
      angioplasty.
AB  - AIM: The safety and efficacy of ad hoc PTCA has been previously reported and this
      approach is performed in many angioplasty centers as a routine procedure. The aim
      of this study is to examine whether this approach reduces the length, and cost of
      hospital stay. METHODS AND RESULTS: To determine the hospital costs we studied
      2,440 PTCAs over 11 years in our institution (1990-2000). Urgent PTCA for acute
      coronary syndromes refractory to medical treatment were excluded. In 1809
      patients (74%) angioplasty was performed immediately after coronary angiography,
      while separate procedures were performed in 631 patients. Indication for PTCA was
      unstable angina in 1342 patients (55%). In the ad hoc PTCA group, 92% of the
      culprit lesions were successfully treated; complications included myocardial
      infarction (2%), urgent bypass surgery (0.6%) and death (0.9%). The rate of
      combined procedure progressively increased from 54% in 1990 to 88% in 2000, with
      a significant decrease in the rate of complications. After adjusting for clinical
      and angiographic differences between combined and separate procedures,
      angiographic success and complication rates were not statistically different in
      the two groups. Mean length of hospital stay decreased all along the years, and
      was 45% less in the ad hoc PTCA group (11.4 +/- 6.9 vs 18.2 +/- 7.7 in 1990, 5.4
      +/- 4.3 vs 10.8 +/- 5.7 in 2000, P < 0.0001). The cost was 40% lower in the ad
      hoc PTCA group. For patients with stable angina, the savings were 49%, and for
      those with unstable angina, they were 29%. CONCLUSION: In the era of coronary
      stenting, ad hoc PTCA can be performed in most of the patients as safely and
      successfully as a separate procedure. It reduces the length, and the cost of
      hospital stay in patients with stable or unstable angina.

PMID- 12800397
TI  - Acute myocardial infarction complicated by early onset of heart failure: safety
      and feasibility of interhospital transfer for coronary angioplasty. Subanalysis
      of Killip II-IV patients from the PRAGUE-1 study.
AB  - OBJECTIVE: The objective of this study is to assess the feasibility and safety of
      interhospital transfer (within up to 60 minutes) for primary/rescue coronary
      angioplasty of patients with myocardial infarction (AMI) complicated by an early
      onset of acute heart failure (AHF) admitted to a community hospital without PCI
      facilities. DESIGN AND PATIENTS: From the multicenter randomized PRAGUE-1 study,
      a subgroup of 66 patients with AMI complicated by AHF on the first presentation
      to the community hospital were retrospectively analyzed. Group A patients (n =
      21) were treated on site in community hospitals using thrombolysis
      (streptokinase), group B patients (n = 20) were transported with thrombolytic
      infusion to a PCI center for coronary angioplasty, and group C patients (n = 25)
      were immediately transported to a PCI center for primary angioplasty without
      thrombolysis. RESULTS: No patient died during transportation. One group B patient
      developed ventricular fibrillation during transfer. The time delay from the onset
      of chest pain to reperfusion was > 142 minutes, and 253 and 251 minutes in groups
      A, B, and C, respectively. Hospital stay (16 vs 11 vs 10 days, P = NS) was
      shorter in the angioplasty groups. Transported patients (groups B, C) displayed a
      significant decrease in heart failure progression within the first 24 hours after
      treatment (48% vs 15% vs 8%, P < 0.05). The combined end point, i.e., mortality +
      nonfatal reinfarction (43% vs 25% vs 8%, P < 0.05), was significantly less
      frequent in the coronary angioplasty group. CONCLUSIONS: Interhospital transfer
      for coronary angioplasty of patients with AMI complicated by an early onset of
      AHF is feasible and safe. Transport for angioplasty may even reduce the risk of
      heart failure progression and improve clinical outcome compared to immediate
      thrombolysis in the nearest community hospital.

PMID- 12800399
TI  - A randomized comparison of a percutaneous suture device versus manual compression
      for femoral artery hemostasis after PTCA.
AB  - BACKGROUND: The prolonged bed rest following femoral sheath removal after PTCA is
      a source of discomfort for the patient. We designed a randomized study to
      evaluate the efficacy and safety of an arterial suture device developed to
      percutaneously close the vascular access site after PTCA, allowing immediate
      sheath removal and early ambulation, compared to manual compression. METHODS:
      After successful PTCA, patients were randomized to manual compression or
      immediate femoral percutaneous closure. Exclusion criteria were arteritis, age >
      80 years and > 3 previous femoral punctures on the same side. The two-needle
      device was used for the 6F sheath removal and the four-needle device for the 8F
      sheath. Ambulation was allowed 4 hours after the arterial suture. RESULTS: One
      hundred and sixty-seven patients (59 +/- 10 years, 81% males) were randomized to
      suture device (n = 91) or to manual compression (n = 76). The two groups were
      similar in terms of age, sex, size of sheath, number of patients with stent
      implantation (62 vs 61%), procedural anticoagulation. Procedural duration was 8
      +/- 6 minutes with percutaneous suture versus 25 +/- 11 minutes with manual
      compression (P < 0.0001). Procedural success with percutaneous suture was 93%
      whereas six technical failures were treated with prolonged manual compression.
      Nonsurgical hematoma occurred in five patients (5%) with the suture device and in
      two (3%) with manual compression with no need for blood transfusion (P = NS).
      Uneventful blood oozing occurred in 11 patients (12%) with percutaneous suture
      and in only 2 (3%) with manual compression (P < 0.06). The tolerance of the
      hemostasis procedure and the length of post-procedure hospital stay (40 +/- 32
      hours) were similar in the two groups. CONCLUSION: Percutaneous suture of the
      femoral artery, allows immediate closure of femoral puncture sites after PTCA,
      without increasing the incidence of vascular complications. The use of this
      device should allow earlier discharge and subsequent cost savings.

PMID- 12800398
TI  - The long-term clinical outcomes after rescue percutaneous coronary intervention
      in patients with acute myocardial infarction.
AB  - Rescue percutaneous coronary intervention (PCI) has been used to treat patients
      after failed thrombolysis in acute myocardial infarction. However, the short- and
      long-term benefits of rescue PCI have not been known exactly. The goal of this
      study was to examine the clinical and angiographic outcomes, the success rate of
      the procedure, and the long-term survival rate after rescue PCI. The clinical and
      angiographic outcomes of 31 patients (Group I; 59.7 +/- 11.4 years, 80.6% male),
      who underwent rescue PCI were compared with those of 177 patients (Group II; 59.7
      +/- 9.7 years, 79.7% male), who underwent primary PCI at Chonnam National
      University Hospital between January 1997 and December 1999. There were no
      significant differences in the risk factors for coronary artery diseases except
      for smoking (Group I; 24/31, 77.4% vs. Group II; 76/177, 42.9%, P = 0.011). The
      incidence of cardiogenic shock was higher in Group I than in Group II (Group I;
      7/31, 22.6% vs. Group II; 11/177, 6.2%, P = 0.021). The coronary angiographic
      findings were not different between two groups, except for Thrombolysis in
      Myocardial Infarction (TIMI) flow of Group I was lower than in Group II (Group I;
      1.14 +/- 0.93 vs. Group II; 1.61 +/- 1.14, P = 0.001). The primary success rate
      was 93.6% (29/31) in Group I and 94.9% (168/177) in Group II (P = 0.578). The
      baseline ejection fraction was lower in Group I than in Group II (Group I; 44.2
      +/- 8.9% vs. Group II; 50.8 +/- 11.7, P = 0.023), which improved in both groups
      (Group I; 51.7 +/- 7.9% vs. Group II; 60.7 +/- 13.4%, P = 0.001 respectively) at
      6 months after the procedures. The survival rates of Group I were 93.5%, 93.5%,
      and 90.3% and those of Group II were 94.5%, 93.7%, and 91% at 1, 6, and 12
      months, respectively. Rescue PCI is associated with the risk factor of smoking.
      The indication for rescue PCI was more common in patents with cardiogenic shock.
      The success rate of rescue PCI was comparable to that of primary PCI, and left
      ventricular function is improved after rescue PCI on long-term clinical follow-up
      with relatively high survival rate.

PMID- 12800400
TI  - Simple technique to ensure coaxial guidewire positioning for placement of iliac
      limb of modular aortic endograft.
AB  - Endovascular abdominal aortic aneurysm repair using a modular bifurcated stent
      graft requires the initial placement of the main component in the infrarenal
      aorta, followed by insertion of additional iliac stent-graft(s) to exclude
      aneurysm and to securely affix the device. Placement of the contralateral iliac
      component within the main bifurcated device is critical in this endovascular
      procedure, as malpositioning of the contralateral iliac limb can require
      conversion to open aneurysm repair. A simple adjunctive technique utilizing a
      rotational maneuver of a pigtail catheter is described. This maneuver reliably
      confirms the proper placement of the contralateral iliac stent-graft within the
      main bifurcated device.

PMID- 12800401
TI  - Stenting for restenotic lesions with the BARD XT stent.
AB  - BACKGROUND: Conventional PTCA for the treatment of restenotic lesions is
      associated with a high rate of recurrence (30-50%). Primary stenting decreases
      the restenosis rate at long-term follow-up. METHODS: One-hundred consecutive
      patients with restenosis received a Bard XT stent. Follow-up angiography was
      performed after 6 months. Angiograms were compared by means of computed
      quantitative analysis. RESULTS: The mean pretreatment reference diameter was 2.88
      +/- 0.51 mm. The mean minimal luminal diameter (MLD) increased from 1.09 +/- 0.57
      mm to 2.70 +/- 0.44 mm. The percent diameter stenosis decreased from 66 +/- 13%
      to 15 +/- 10%. The procedural success rate was 99%. At 6 month follow-up repeat
      angiography was performed in 86 patients. The mean MLD was 1.74 +/- 0.67 mm with
      a mean diameter stenosis of 41 +/- 20%. Residual anginal complaints were reported
      in 29% of patients. In-stent restenosis (defined as diameter stenosis of more
      than 50%) occurred in 18% of the patients. CONCLUSION: Placement of the Bard XT
      stent in restenotic lesions is feasible, has an excellent short term outcome and
      yields a favorable result at 6 month follow-up angiography.

PMID- 12800402
TI  - Detecting vulnerable plaque using peripheral blood: inflammatory and cellular
      markers.
AB  - The concept of the vulnerable patient has arrived. Enhanced diagnostic methods
      will eventually permit accurately finding and treating these patients and their
      disease. Clinical Cardiologists now recognize that coronary atherosclerosis is
      two pathophysiologically distinct syndromes: stable and unstable. Stable coronary
      syndromes result from fixed, severe stenoses limiting blood flow and causing
      secondary myocardial ischemia. The unstable acute coronary syndromes are
      frequently catastrophic and are pathophysiologically distinct. They result from
      different cell subsets causing vascular inflammatory syndromes rather than
      gradual lumen constriction by plaque. Though pathophysiologically distinct, they
      may show common pathophysiology when a ruptured plaque heals and progressively
      becomes a critical stenosis. For the present hs-CRP measurement is the strongest
      correlative factor for future clinical events due to arterial inflammation:
      myocardial infarction, unstable angina, stroke, and peripheral vascular disease
      in both diseased and apparently healthy, asymptomatic patients. The CRP plasma
      level also is the best risk assessment in patients with either stable or unstable
      angina, long term after myocardial infarction, and in patients undergoing
      revascularization therapies. One study showed the only independent cardiovascular
      risk indicators using multivariate, age adjusted and traditional risk analysis
      were CRP and Total/HDL cholesterol ratio. If CRP, IL-6, and ICAM-1 levels are
      added to lipid levels, risk assessment can be improved over lipids alone. The
      prevalence of high-risk subjects in the general population is low, amplifying
      diagnostic problems for vulnerable plaque. Since no test yet has high sensitivity
      or specificity, diagnostic errors are high, with many false positives and
      negatives. Sensitivity or specificity must be increased by developing a risk
      marker panel, or by simultaneously finding other markers that themselves are
      highly sensitive and specific for vulnerable plaque.

PMID- 12800403
TI  - Detection of high-risk atherosclerotic coronary plaques by intravascular
      spectroscopy.
AB  - Multiple technologies are under development to identify plaque composition and
      vulnerability. This review article is intended to provide basic knowledge to the
      interventional cardiologist and the clinician about spectroscopy. The concept of
      light, the wavelength unit and the electromagnetic spectrum are discussed.
      Different types of spectra analysis including nuclear magnetic resonance, Raman,
      fluorescence and diffuse reflectance near-infrared spectroscopy are then
      carefully reviewed. Experimental data to identify atherosclerotic plaque
      composition for each of these techniques is provided. Potential benefits and
      challenges are addressed. Finally, diffuse reflectance near-infrared spectroscopy
      is discussed in more detail as a promising technique to characterize plaque
      vulnerability in humans.

PMID- 12800404
TI  - Intravascular elastography: from bench to bedside.
AB  - An unstable lesion may rupture and cause an acute thrombotic reaction. These
      lesions contain a large lipid pool covered by a thin fibrous cap. The stress in
      the cap increased with decreasing thickness and increasing macrophage
      infiltration. Intravascular ultrasound (IVUS) elastography might be an ideal
      technique to assess the presence of lipid pools and identify high stress regions.
      Elastography assesses the local mechanical properties of tissue using its
      deformation caused by the intraluminal pressure. The technique was validated in
      vitro using diseased human coronary and femoral arteries. These experiments
      demonstrated that the strain in the three plaque types is different (P < 0.001).
      Especially between fibrous and fatty tissue, a highly significant difference (P =
      0.0012) was found. Additionally, the predictive value for identifying the
      vulnerable plaque was investigated. A high strain region at the lumen vessel wall
      boundary has 88% sensitivity and 89% specificity for identifying these plaques.
      In vivo, the technique is validated in an atherosclerotic Yucatan mini-pig animal
      model. This study also revealed higher strain values in fatty than fibrous
      plaques (P < 0.001). The presence of a high strain region at the lumen plaque
      interface has a high predictive value for identifying macrophages. Patient
      studies revealed high strain values (1-2%) in soft plaques. Calcified material
      shows low strain values (0-0.2%). With the development of three-dimensional
      elastography, identification of weak spots over the full length of a coronary
      artery becomes possible. In conclusion, intravascular elastography is a unique
      tool to assess lesion composition and vulnerability. The development of three
      dimensional elastography provides a technique that may develop into a clinical
      available tool for identifying the rupture-prone plaque.

PMID- 12800405
TI  - Arterial wall thermography.
AB  - An atherosclerotic plaque is considered vulnerable when it is at higher risk of
      inducing acute cardiac events. The early detection and follow-up of the
      vulnerable plaque are crucial to prevent these events from happening. To date
      there are no proven techniques to detect such a plaque. Arterial wall
      thermography, tracing the heat signature of the activated macrophages, is a new
      and promising method in this direction. However, the difficulties of applying
      such a method in vivo should not be neglected. Current science proposes several
      potential thermographic methods. They can be generally categorized as noninvasive
      and invasive. Magnetic resonance thermometry (MRT) is the most important
      noninvasive method. It is novel, accurate, and reproducible, but is unfortunately
      hampered by resolution limitations due to the size and motion of the target
      vessels. The "infrared" and the "contact-sensor" are the most important invasive
      thermographic methods. Mainly due to the difficulties of infrared radiation in
      penetrating the flowing blood, the contact thermographic methods seem to be the
      most feasible at present. The superiority of thermal mapping of the arterial wall
      versus the localized temperature measurements is clear. The use of multiple
      thermal sensors arranged around the vessel's circumference and the application of
      motorized catheter pullback, not only ensure a large area of coverage, but also
      enable us to build thermal maps and vascular thermoanatomical reconstructions by
      using modern computer technology. It is expected that arterial thermography will
      undoubtedly initiate debate, mainly concerning the most appropriate therapy for
      the vulnerable plaque. Data collection and correct interpretation are expected to
      lead us into making wise decisions.

PMID- 12800406
TI  - Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque.
AB  - Thin cap atheroma is the precursor of plaque rupture, which accounts for a
      majority of coronary thrombi. The morphologic features of thin cap atheromas that
      predict rupture are unknown, but we know from studies of ruptured plaques that
      large necrotic cores, fibrous cap < 65 microns and numerous macrophages within
      the cap likely indicate instability. There is some evidence that a speckled
      pattern of calcification is associated with vulnerability to rupture. There are
      usually multiple thin cap atheroma in the hearts of patients dying with acute
      plaque rupture, as well as multiple fibroatheromas with intraplaque hemorrhage.
      Targeted therapy for the purpose of stabilizing coronary lesions that are prone
      to rupture is a major future goal of the interventionist.

PMID- 12800407
TI  - Vulnerable plaque: the challenge to identify and treat it.
AB  - In order to understand, treat, and prevent acute coronary syndromes we need to
      improve our ability to identify the rupture-prone, vulnerable atherosclerotic
      coronary plaque. The diagnostic modalities that are currently available to
      clinical practice have not fulfilled this expectation, and newer diagnostic
      techniques based on the recently identified features of the vulnerable plaque are
      quite promising. Coronary angiography, intravascular ultrasound, and angioscopy
      have been used in the clinical arena of interventional cardiology with several
      limitations regarding the identification of the vulnerable plaque. Thermography,
      optical coherence tomography, elastography, Raman spectroscopy, and infrared
      spectroscopy are used in clinical trials and the results are encouraging.
      Ultrafast computed tomography and magnetic resonance imaging have the advantage
      of being noninvasive. With our progress in the identification of the rupture
      prone vulnerable coronary plaque, we will be able to identify patients that are
      at high risk and will benefit from a more aggressive therapeutic approach.

PMID- 12800408
TI  - Percutaneous intervention of unprotected left main coronary artery.
AB  - Successful percutaneous intervention of unprotected left main coronary artery
      (LMCA) in lieu of surgical revascularization represents the next wave of
      challenges that the field of interventional cardiology will try to overcome.
      Significant LMCA stenosis, commonly secondary to atherosclerosis, is seen in
      about 4-10% of cases presenting to the cardiac catheterization laboratory.
      Currently, the vast majority of these patients undergo surgical revascularization
      unless there are prohibitive reasons for surgical revascularization. Several
      challenges of percutaneous revascularization have been overcome with stents,
      intravascular brachytherapy, and other technical improvements. Yet, several
      remaining limitations of percutaneous intervention, such as in-stent restenosis,
      have to be improved further before randomized clinical trials of surgical and
      percutaneous revascularization of unprotected LMCA disease can be contemplated to
      establish a new standard of care.

PMID- 12800409
TI  - [Evaluating the complexities of the development of botanical medicine].

PMID- 12800410
TI  - [Provide against possible trouble--on knowledge, prevention and treatment of
      adverse drug reactions].

PMID- 12800411
TI  - [A comparative study of manchurian Dutchmanspipe and antibiotics induced acute
      tubular necrosis in renal cellular biological features].
AB  - OBJECTIVE: To explore the possible cell biological mechanisms of the difference
      in prognosis between the acute tubular necrosis (ATN) induced by Manchurian
      Dutchmanspipe (MD-ATN) and that by antibiotics (A-ATN), by means of comparing
      their renal tubular mesenchymal cell phenotype characteristics and extra-cellular
      stroma secretion. METHODS: The expression of proliferative cell nuclear antigen
      (PCNA), epithelial cell growth factor (EGF), alpha-smooth muscle actin (alpha
      SMA), fibronectin (FN), collagen type III and IV, transforming growth factor beta
      1 (TGF beta 1) and connective tissue growth factor in renal biopsy samples of
      patients with MD-ATN (4 patients) and A-ATN(5 patients) were compared with
      immunohistochemical SP method. The analysis of above-mentioned parameters on
      repairing of injury and development of fibrosis was stressed for the obvious
      difference in clinical prognosis between the two groups. RESULTS: (1) The PCNA
      positive rate of renal tubular epithelial cell (RTEC) and EGF expression in the
      MD-ATN group were significantly lower than those in the A-ATN group respectively
      (P < 0.01); (2) Renal tubular mesenchymal alpha-SMA level increased in both
      groups with no significant difference; (3) TGF beta 1 positive cell infiltration
      and obvious CTGF expression revealed in renal mesenchyma of both groups with
      insignificant difference; (4) FN, collagen III and IV levels were significantly
      higher in the MD-ATN group than that in the A-ATN group (P < 0.05). CONCLUSION:
      (1) As compared with A-ATN group, the RTEC auto-repairing ability was lower in
      the DM-ATN group, lower expression of EGF might be one of the mechanisms of its
      poor repair; (2) High expression of alpha-SMA, TGF beta 1 and CTGF presented in
      all patients with ATN, but extra-cellular stromal deposit appeared only in the
      renal stroma of patients with MD-ATN, suggesting that its chronical trend might
      be related with the reducing of extra-cellular stromal degradation factor and/or
      endogenous anti-fibrosis factor.

PMID- 12800412
TI  - [Clinical observation on effect of taizhi'an capsule in treating 150 patients
      with hyperlipidemia].
AB  - OBJECTIVE: To grasp the therapeutic effect of Taizhi'an (TZA) in lowering blood
      lipid level. METHODS: Three hundred patients with hyperlipidemia were randomly
      divided adopting numerical table method into 7 groups, the Taizhi'an group (A, n
      = 90), the half-dose Fenofibrate plus Taizhi'an group (B, n = 30), the full-dose
      Fenofibrate group (C, n = 30), the half-dose Simvastatin plus Taizhi'an group (D,
      n = 30), the full-dose Simvastatin group (E, n = 30), the Zhibituo group (F, n =
      60) and the Xuezhikang group (G, n = 30). The effect in different groups were
      compared after 8 weeks treatment. RESULTS: In group A, the total cholesterol (TC)
      lowered by 12.7%, triglyceride (TG) lowered by 22.1% and the high density
      lipoprotein cholesterol (HDL-C) increased by 13.1%, the total effective rate
      being 82%. The therapeutic effect in group B was similar to that in group C, and
      that in group D was similar to that in group E (P > 0.05). The therapeutic effect
      of Taizhi'an was similar to that of Xuezhikang and Zhibituo, but was better than
      Zhibituo in lowering TG, LDL-C and increasing HDL-C, and better than Xuezhikang
      in lowering TG and increasing HDL-C (P < 0.05). CONCLUSION: When Taizhi'an used
      in combination with half-dose Simvastatin, it could not only enhance the blood
      lipid regulatory effect of Simvastatin but also reduce the dosage used and
      alleviate its adverse reaction. Compared with Xuezhikang and Zhibituo, Taizhi'an
      got the similar therapeutic effect, but was superior in regulating blood lipids.

PMID- 12800413
TI  - [An investigation on clinical studies of TCM in preventing and treating angina
      pectoris of coronary heart disease].
AB  - OBJECTIVE: To analyze the current status of clinical studies of TCM in preventing
      and treating angina pectoris of coronary heart disease. METHODS: A statistical
      analysis of articles regarding the use of TCM in preventing and treating angina
      pectoris, published in TCM core journals or journals of TCM university (college)
      from January 2001 to June 2002 was conducted, the items analyzed included the
      differentiation of stable angina (SA) and unstable angina (UA), the grading or
      stratifying, standard for therapeutic efficacy evaluation, standardized drug
      therapy of UA (according to the "Suggestion on the diagnosis and treatment of UA"
      formulated by Society of Cardiovascular Disease, Chinese Medical Association,
      etc. RESULTS: From the 44 articles that retrieved, UA and SA was not differed in
      29 articles (65.9%), among which 11 articles came from provincial, national TCM
      institute or hospital affiliated to TCM university (college). In the 34 articles
      dealing with UA, only 3 articles mentioned the standardized drug therapy.
      Standard of therapeutic efficacy evaluation announced in 1979 was used in 35
      articles (79.5%). CONCLUSION: Most articles dealing with clinical study on TCM
      prevention and treatment of angina pectoris, UA and SA, have the flaws of un
      standardized, lacking in compact and insufficient science. Improvement of related
      standard for clinical therapeutic efficacy evaluation needs to be further
      perfected.

PMID- 12800414
TI  - [Observation on effect of electro-acupuncture in treating maxillofacial
      hemangioma].
AB  - OBJECTIVE: To investigate the clinical effect of electro-acupuncture (EA) in
      treating maxillofacial hemangioma (MFH). METHODS: The platinum needles
      (electrode) were inserted into the MFH under location and guidance with B
      ultrasonography or CT, with the number of needles used according to the size of
      the MFH to make the distance between needles about 1.5 cm, and the peri-lesional
      health tissue was protected with plastic insulating tube. The electrodes, which
      were divided as cathode and anode, were linked with the EA apparatus for EA
      treatment, the often applied voltage was 5.0-7.0 V, current 60-80 mA and quantity
      about 100 coulombs/cm of MFH's diameter. B-ultrasonography was used for
      monitoring during EA, and the treatment would be finished when B-ultrasonography
      showed disappearance of blood flow. RESULTS: Evaluation according to the WHO's
      standard for therapeutic efficacy evaluation of tumor showed that after
      treatment, 345 patients (85.2%) were completely remitted (CR), 39(9.6%) partially
      remitted (PR), 12(3.0%) improved pathologically, and 9 (2.2%) ineffective, the
      effective rate (CR + PR) was 94.8%. CONCLUSION: EA, as an creative technique for
      treatment of MFH, has made breakthrough achievement in clinical practice with
      high efficacy. It also has the superiorities of simple, less injury, quick
      recovery, with no scar left and easy to be spread, therefore, it provides an
      effective method for curing MFH.

PMID- 12800415
TI  - [Effect of manshuailing oral liquid on left ventricular diastolic dysfunction in
      patients with heart disease of Xin-Shen Yang deficiency type].
AB  - OBJECTIVE: To investigate the effect of Manshuailing Oral Liquid (MSL) on left
      ventricular diastolic dysfunction (LVDD) in patients with heart disease. METHODS:
      Ninety patients with LVDD were randomly divided into the conventional treated
      group (Group A, treated by conventional treatment with western drugs of
      cardiotonic, diuretic, coronary dilator, etc.) and the Chinese drug treated group
      (Group B, treated by conventional treatment plus MSL 2 times a day, 100 ml each
      time), 45 in each group. After 4 months treatment, the total heart failure
      coefficient (HFC) and cardiac functions were re-determined. RESULTS: After
      treatment, in both groups, the HFC lowered significantly (P < 0.05 or P < 0.01),
      the left ventricular peak velocity of early diastolic rapid filling (Emas)
      quickened, the left atrial systolic peak velocity (Amas) slowed down and
      Emas/Amas (E/A) enhanced, the isovolumetric relaxation time shortened. However,
      comparison between the two groups showed significant difference (P < 0.05) in
      either item, Group B was superior to Group A (P < 0.05). In the 62 patients with
      mixed heart failure, i.e. both systolic and diastolic dysfunction of left
      ventricle, Group B was superior to Group A in increasing ejection fraction,
      cardiac output and thickening rate of left ventricular posterior wall (P < 0.05).
      CONCLUSION: MSL could improve the heart function of patients with LVDD, and
      alleviate their clinical symptoms.

PMID- 12800416
TI  - [Clinical study on effect of shengmai injection on serum concentration and
      pharmacokinetic parameters of digoxin in patients with congestive heart failure].
AB  - OBJECTIVE: To investigate the effect of Shengmai Injection (SMI) on serum
      concentration and pharmacokinetic parameters of digoxin in patients with
      congestive heart failure. METHODS: Forty in-patients with congestive heart
      failure were selected and randomly divided into 4 groups, the three treated
      groups I, II and III treated with digoxin combined with 20 ml, 40 ml and 60 ml of
      SMI respectively, and the control group, 10 patients in each group. The serum
      concentration of digoxin at different time points was determined with
      radioimmunoassay and the pharmacokinetical parameters were calculated with 3P97
      pharmacokinetic software. RESULTS: The serum concentration of digoxin in the
      treated group I was significantly lower than that in the control group (P <
      0.05), with the pharmacokinetical parameters, including the elimination half-life
      time (T1/2), elimination rate constant (Ke), apparent volume of distribution
      (Vd), plasma clearance (CL) and area under curve (AUC), significantly different
      to those in the control group (P < 0.05 or P < 0.01). But the serum concentration
      of digoxin with its pharmacokinetical parameters in the other two treated groups
      were not different significantly to those in the control group respectively (P >
      0.05). CONCLUSION: SMI could influence the metabolism of digoxin in patients with
      congestive heart failure. This study has provided an important reference for safe
      and rational combined use of digoxin and SMI in clinical practice.

PMID- 12800417
TI  - [Effect of astragalus injection on immune function in patients with congestive
      heart failure].
AB  - OBJECTIVE: To study the effect of Astragalus Injection (AI) on the humoral
      immunity (IgG, IgA and IgM), cellular immunity (T-lymphocyte subsets) and soluble
      interleukin-2 receptor (sIL-2R) in patients with congestive heart failure (CHF).
      METHODS: Sixty-two in-patients with CHF, whose heart function belonged to NYHA
      grade II-IV, were randomly divided into two groups. The treated group was treated
      with AI 30 ml (equivalent to 60 g crude drug), and the control group was treated
      by nitroglycerine injection 10 mg, the drugs were administered respectively by
      adding in 5% glucose solution 500 ml for intravenous dripping, once a day, 20
      days as one therapeutic course. Venous blood from cubital vein was collected
      before and after treatment to detect the IgG, IgA, IgM, T-lymphocyte subsets and
      sIL-2R, and the clinical effect of treatment was evaluated. RESULTS: The clinical
      heart function markedly improved rate and total effective rate in the treated
      group was 25.8% and 74.2% respectively, significantly better than those in the
      control group respectively (P < 0.05 or P < 0.01), the left ventricular ejecting
      fraction (LVEF) and end syctolic volume (ESV) were improved in both groups (P <
      0.05, P < 0.01), and the improvement in the treated group was superior to that in
      the control group (P < 0.05). In the treated group after treatment, the CD4 level
      and CD4/CD8 ratio increased (P < 0.05), levels of sIL-2R, IgG and IgA lowered (P
      < 0.05) significantly, while those in the control group were not changed
      significantly (P > 0.05). CONCLUSION: AI could improve the immune function of CHF
      patients, and can be taken as an important auxiliary treatment for CHF.

PMID- 12800418
TI  - [Effect of jiawei mojie tablet on plasma oxytocin level in patients with primary
      dysmenorrhea in menstrual period].
AB  - OBJECTIVE: To investigate the therapeutic mechanism of Jiawei Mojie Tablet (JMT)
      in treating primary dysmenorrhea (PD) by observing its effect on plasma oxytocin
      (OT) level in patients in menstrual period. METHODS: Sixty-three patients with PD
      enrolled in the study were randomly divided into the JMT group (n = 33) and the
      control Group (n = 30, treated with Yueyueshu Granule) to observe the change of
      OT level in the menstrual period before and after treatment. RESULTS: OT level in
      patients with PD was obviously higher than that in healthy subjects (P < 0.01),
      and was positively correlated with the degree of pain (r = 0.738, P < 0.01). OT
      level reduced significantly after treatment (P < 0.01), the reduction was more
      significant in the JMT group than that in the control group (P < 0.01).
      CONCLUSION: JMT could reduce the OT level in menstrual period.

PMID- 12800419
TI  - [Preliminary study on effect of ganhuang injection on reject reaction of
      xenograft].
AB  - OBJECTIVE: To study the effect of Ganhuang Injection (GHI) on reject reaction of
      xenograft. METHODS: RT-PCR technique was used to detect the activated relevant
      gene expression in porcine endothelial cells (PEC), and 51Cr releasing method was
      used to test the killing and adhesion action of NK cells. RESULTS: The normal
      human serum and human NK-92 cell could up-regulate the mRNA expressions of E
      selectin and IL-1 alpha gene in PEC, showing the PEC activating action, GHI could
      inhibit these activated gene expressions. Cyto-toxic experiment showed that GHI
      could also inhibit the cytotoxicity of NK cell on PEC dose-dependently, which was
      in accord with its inhibition on adhesive action of NK on PEC. CONCLUSION: GHI
      could inhibit not only the PEC activation in hyperacute rejection, but also the
      function of NK cells in delayed xenograft rejection.

PMID- 12800421
TI  - [Regulatory effect of clearing-heat secreting-bile regulating-qi flow and
      activating blood circulation principle on cholecystokinin receptor].
AB  - OBJECTIVE: To explore the regulatory effect of clearing-Heat secreting-bile
      regulating-Qi flow and activating blood circulation (CSRA) principle on
      cholecystokinin receptor (CCK-R) and its mechanism. METHODS: Cholecystokinin
      (CCK) in serum of portal venous blood, maximum binding capacity (Bmax) and
      affinity (Kd) of CCK-R levels in gallbladder of guinea pigs allocated in four
      groups (control, high cholesterol, natural recovery and treated groups) were
      determined using radioimmunoassay and radioligand receptor assay (RRA). At the
      same time, changes of fasting volume (FV) and postprandial volume (PV) of
      gallbladder, fasting and postprandial bile (FB and PB) in gallbladder,
      gallbladder contraction rate (GCR) and cholesterol concentration (CC) in bile
      were observed. RESULTS: Compared with the control group, after two weeks of high
      cholesterol feeding, increase of FV, FB, PV, PB and CC (P < 0.05), and decrease
      of GCR (P < 0.01) and Bmax were found in cholesterol group, but with no
      significant change in Kd and CCK level. The above-mentioned criteria were
      restored to normal range in the treated group. CONCLUSION: CSRA principle could
      promote the recovery of gallbladder contraction by regulating CCK-R expression in
      it, its mechanism is possibly correlated with reduction of cholesterol
      concentration in bile.

PMID- 12800420
TI  - [Study on free radical mechanism of guanxin II in antagonizing ischemic
      myocardial damage].
AB  - OBJECTIVE: To study comparatively the effect of Guanxin II and its constituents,
      including Salvia, Red Peony root, Chuanxiong, Safflower and Dalbergia wood, in
      scavenging active oxygen free radical (OFR) to explore their mechanism in
      overcoming the experimental acute ischemic myocardial injury and protecting
      myocardial tissue. METHODS: The experimental acute myocardial ischemic model was
      established by intraperitoneal injection of pituitrin to rats. OFR level in
      animal heart tissue was directly measured with low-temperature electron
      paramagnetic resonance (EPR) spectrometer. RESULTS: The pathological examination
      of HE stained slide of myocardial tissue and electrocardiography of model animal
      showed that typical changes of acute myocardial ischemia occurred in myocardial
      tissue, EPR showed that OFR level in myocardial tissue increased abnormally. The
      ethanol extract of Guanxin II and its constituents could lower the increased OFR
      level close to normal, thus to alleviate the myocardial damage. CONCLUSION:
      Overproduction of OFR could induce damage of heart tissue, its level could be
      measured directly using low temperature EPR. One of the molecular mechanisms of
      Guanxin II and its constituents in antagonizing and repairing myocardial damage
      is to scavenge the abnormal increased active OFR in tissue. This study has
      provided a basis for further studying the mechanism of Chinese composite recipes
      and their constituents.

PMID- 12800422
TI  - [Effect of sappan wood on perforin mRNA expression in myocardium of rats after
      allogeneic cardiac transplantation].
AB  - OBJECTIVE: To observe the effect of Sappan wood (SW) on the expression of
      perforin mRNA in myocardium of rats after allogeneic cardiac transplantation.
      METHODS: The animal model of allogeneic (abdominal) cardiac transplantation was
      established by taking Wistar rat as provider and SD rat as receptor, perforin
      mRNA expression in the model's myocardium was detected by RT-PCR. RESULTS: SW
      could obviously reduce the perforin mRNA expression, it also could alleviate the
      pathological morphology and ultrastructural damage of myocardial cells.
      CONCLUSION: SW has obvious effect in antagonizing immune rejection after
      transplantation, the mechanism of its immunosuppression could be through lowering
      the perforin mRNA expression.

PMID- 12800423
TI  - [Clinical application and pharmacological actions of ligustrazine].

PMID- 12800424
TI  - [Clinical observation on effect of combined use of Astragalus and compound
      salviae injection in treating acute cerebral infarction].

PMID- 12800425
TI  - [Clinical observation of chemotherapy combined with yiqi xiaozheng granule in
      treating advanced malignant tumor].

PMID- 12800426
TI  - [Clinical observation on effect of modified biyusan in treating 69 patients with
      chronic arsenic intoxication].

PMID- 12800427
TI  - [Progress on TCM drug-therapy of antagonizing arteriosclerosis].

PMID- 12800428
TI  - [Minute on 6th National Integrative Medical Conference of Cardiovascular
      Diseases].

PMID- 12800429
TI  - Severe acute respiratory syndrome (SARS).

PMID- 12800430
TI  - Progress in reducing global measles deaths.

PMID- 12800431
TI  - Ethics and the architect.

PMID- 12800432
TI  - Both new and improved advances in seismic technologies promise safer buildings.
      Since most regions of the U.S. are vulnerable to earthquakes, architects must
      respond.

PMID- 12800434
TI  - Not-for-profits are likely to adopt new fiscal rules. SEC's financial-reporting
      policy affects for-profits, but others wonder whether they could benefit, too.

PMID- 12800433
TI  - The other shoe drops. Barbakow, already set to lose chairman's seat, out as
      Tenet's CEO; shareholders, analyst call for outsider as his replacement.
AB  - What a difference a year makes. For many, it wasn't a total surprise when Jeffrey
      Barbakow, the leader of Tenet Healthcare Corp., stepped down last week from the
      company he headed during a period of glowing prosperity. But as he departs, Tenet
      is surrounded by a tempest similar to the one that led to his hiring.

PMID- 12800435
TI  - NCFE fallout continues. Banks, accounting firms, execs charged in lawsuit.

PMID- 12800436
TI  - Slow recovery. Patient dumping settlements plunge; experts remain mixed on
      factors.

PMID- 12800437
TI  - Bittersweet. AMA reaps profits despite decreasing membership.

PMID- 12800438
TI  - Sharing is caring. Basic medical info must be standardized so docs can pass along
      care details.

PMID- 12800439
TI  - Not making the grade. Quality information is too difficult to understand.

PMID- 12800440
TI  - Info-tech gets a jump-start.

PMID- 12800441
TI  - A new era. Hospitals cope with ailing investment portfolios.

PMID- 12800442
TI  - Trickling down. Strong operational improvements at healthcare systems once again
      fail to show up on the bottom line, according to Modern Healthcare's annual
      survey.

PMID- 12800443
TI  - Strong tenets. For the acting CEO at no. 2 hospital chain, three R's could be
      relationships, risk-taking and responsibility.

PMID- 12800444
TI  - [Travel related thrombosis: media horror scenario or medical fact?].

PMID- 12800445
TI  - The epidemiology of medical errors: a review of the literature.
AB  - BACKGROUND: Medical errors are one of the most important quality problems in
      health care today. The best insight into the incidences and characteristics of
      medical errors is through studies on adverse events (AEs) since a considerable
      fraction of AEs are results of errors and as such preventable. Even though
      prevention is where effort should be directed to, only a few studies report on
      the preventability of AEs. Our aim is to give an overview of the literature
      reporting on AEs and their preventability. METHODS: We systematically searched
      Medline and Embase for literature published between 1980 and June 2002. All
      articles reporting primary data on incidences of AEs and their preventability
      were included. RESULTS: The 8 articles retrieved were divided into two
      categories. 1) Four large scale retrospective studies: They reported incidences
      of AEs between 2.9% and 16.6% of all hospitalizations that were judged as
      preventable in 48.0-69.6% and negligent in up to 32.3%. 2) Four prospective
      studies: The reported rates of AEs vary remarkably (0.0037-39.0%) because of
      different detection methods used, different definitions applied and different
      health care settings studied. One prospective observational study identified AEs
      in 39.0% of hospitalized patients with a preventability of 18.0%. Two other
      studies, using process oriented incidence reporting detected rather low rates of
      AEs (4.2-5.4%) which were preventable in up to 62.5%. One prospective study in
      the outpatient setting, using voluntary incidence reporting detected only about
      3.7 events per 100,000 clinic visits of which a high fraction was judged to be
      preventable (83.0%). IMPLICATIONS: Incidence, medical outcome and costs of AEs
      warrant this issue to be high on any countries health care agenda. The U.S.,
      Australia and Britain have adopted this challenge by creating a centre for
      quality improvement and patient safety within the health service and by enacting
      new laws. But real improvement of patient safety will need a fundamental change
      in medicine from a culture of individual blame and guilt to a culture of
      learning, system thinking and executive responsibility.

PMID- 12800446
TI  - Quality of life in nonorganic and organic sleep disorders: II. Correlation with
      objective and subjective quality of sleep and awakening.
AB  - OBJECTIVE: The purpose of this study of 100 patients suffering from sleep
      disorders was to determine correlations between their subjective health-related
      quality of life (HRQoL) and objective variables in sleep initiation and
      maintenance, sleep architecture, objective quality of awakening,
      psychophysiological parameters and subjective quality of sleep and awakening.
      METHODS: Objective measurements were obtained from overnight diagnostic
      polysomnography. Subjective HRQoL was determined from the Quality of Life Index
      (QLI, Mezzich and Cohen) completed prior to the adaptation night. Other
      measurements included subjective and objective quality of sleep and awakening
      (psychometry) the evening before and morning after polysomnographic
      investigations. RESULTS: 63% of the patients were suffering from nonorganic and
      37% from organic sleep disorders (SDs). Within the first group, nonorganic
      insomnia predominated; within the second, sleep apnea. Subjective HRQoL
      correlated well with subjective sleep and awakening quality, especially in
      nonorganic SDs. There were only a few correlations of objective measurements with
      subjective HRQoL: in the total group of SD patients HRQoL correlated with sleep
      stage S2, and in nonorganic SDs with attention scores and psychophysiological
      measurements (mainly the pulse rate in the evening and morning). CONCLUSION: Our
      findings suggest only a weak relationship between objective sleep variables and
      subjective HRQoL in both organic and nonorganic SDs. However, we found various
      significant correlations of HRQoL with subjective measurements of sleep,
      especially in nonorganic SDs.

PMID- 12800447
TI  - The management of patients with heart failure in a Slovenian community hospital:
      what has changed between 1997 and 2000?
AB  - BACKGROUND: Heart failure is a common and serious disease associated with poor
      prognosis. Despite the encouraging results of many clinical trials and the
      availability of published guidelines, epidemiological studies still show a gap
      between recommendations and clinical practice. There is a scarcity of data on
      changes in the management of patients hospitalized with heart failure. AIM: To
      investigate how evidence-based guidelines on heart failure are being followed in
      clinical practice in patients hospitalized for heart failure in a community
      hospital and whether there have been any changes during the period from 1997 to
      2000. METHODS: Two cohorts of patients with heart failure were studied. A
      retrospective analysis of medical charts from patients hospitalized for heart
      failure in 1997 was compared with a prospective registry (EuroHeart Failure
      survey) of patients hospitalized for heart failure during six consecutive weeks
      in April and May 2000. The data on diagnostic and therapeutic interventions
      during hospitalization in both periods were obtained from medical records.
      RESULTS: We included 122 patients, aged 72 +/- 10 years, in 1997 and 126
      patients, aged 73 +/- 12 years, in 2000. There was no significant difference in
      sex, NYHA class on admission, rate of recurrent hospitalizations, hospital stay
      (11.8 +/- 6.2 days vs. 12.8 +/- 9.6 days, respectively) or in-hospital mortality
      (17% vs. 16%). In the year 2000 significantly more patients had an
      echocardiography report than in 1997 (37% vs. 13%, p < 0.001), and they were
      significantly more often discharged with angiotensin-converting enzyme inhibitors
      (48% vs. 30%, p < 0.01) and beta-adrenergic blockers (9% vs. 2%, p = 0.04).
      CONCLUSIONS: A considerable gap exists between evidence-based guidelines on heart
      failure and clinical practice in the management of patients with heart failure in
      a community hospital. There was some improvement between the two observed
      cohorts, but the recommendations were still not adequately implemented in the
      year 2000. Further improvement requires new hospital strategies for the
      management of heart failure and the creation of an outpatient setting.

PMID- 12800448
TI  - HIV infection and sputum-culture conversion in patients diagnosed with
      Mycobacterium tuberculosis: a population-based study.
AB  - OBJECTIVES: To estimate the effect of human immunodeficiency virus infection on
      treatment outcome of anti-tuberculosis therapy at the population level. MATERIALS
      AND METHODS: A retrospective cohort study based on data collected through the
      expanded program on tuberculosis surveillance on all reported and verified cases
      of tuberculosis in the State of North Carolina from 1993 to 1998. Eligible
      patients were sputum-positive at baseline, with known and documented HIV-serology
      status. We analyzed 1030 cases consisting of 210 HIV-positive and 820 HIV
      negative tuberculosis patients. Patients were followed up for 12 months to
      document sputum conversion. RESULTS: Among HIV-infected individuals, 60% (126)
      converted compared to 75% (615) of HIV-uninfected persons. Using the Cox
      Proportional Hazard method to estimate the likelihood of conversion, we found the
      difference in conversion rates to be highly significant (crude hazard ratio =
      0.54, CI = 0.45-0.66). The inverse relationship between HIV-seropositivity and
      sputum conversion still persisted and remained practically unchanged after adding
      potential confounding factors into the model (adjusted hazard ratio = 0.56, 95%
      CI = 0.46-0.69). CONCLUSION: Response to anti-tuberculosis therapy was
      significantly less favorable in HIV-infected than in HIV-uninfected tuberculosis
      patients. The importance of longer and closer monitoring of tuberculosis
      treatment in HIV-positive patients is highlighted.

PMID- 12800449
TI  - Spontaneous dissecting aneurysm of the coronary artery. A rare cause of
      myocardial infarction and sudden death.
AB  - Spontaneous dissecting aneurysm of the coronary artery (SDACA) not associated
      with aortic aneurysm or trauma is a very rare cause of myocardial ischemia. It
      has a higher prevalence in otherwise healthy women, especially in the peri- and
      postpartum period. In 80-90% of cases the diagnosis of SDACA is confirmed at
      autopsy, as the majority of patients present with acute myocardial infarction or
      sudden death. We describe the case of a 47-year-old Caucasian woman who died
      suddenly without any previous sign of cardiac disease. She had no clinical signs
      of Marfan's syndrome or arterial hypertension, she used no oral contraceptives
      and she was not in the peri- or postpartum period. At autopsy we found a recent
      dissecting aneurysm of the right coronary artery. Histology showed a hematoma
      between the media and adventitia of the coronary artery, flattening and occluding
      the lumen. Acute myocardial infarction was present in the posterior wall of the
      left cardiac ventricle. SDACA is an unpredictable condition and prompt diagnosis
      and life-saving procedures--either surgical or conservative--are rarely
      successful. We report a very rare disease documented in only 108 cases according
      to the English-language literature accessible to us.

PMID- 12800451
TI  - A two-tier NHS in a two-tier world--time for change.

PMID- 12800450
TI  - [Consensus recommendations of the Pulmonary Arterial Hypertension Study Group of
      the Austrian Society of Lung Diseases and Tuberculosis].

PMID- 12800452
TI  - Aggressive lipid-lowering therapy in high-risk groups: warranted or excessive?

PMID- 12800453
TI  - The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity
      in type 2 diabetic patients.
AB  - The aim of this study was to evaluate the effect of vitamin D3 supplementation on
      insulin secretion and insulin resistance. Ten females with type 2 diabetes being
      treated with oral hypoglycaemic agents and with normal serum and urine calcium
      levels were enrolled in the study. The study was conducted in March, when levels
      of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured
      (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases
      of insulin secretion were studied during IVGTT. Peripheral insulin resistance was
      measured. A group of 17 age- and BMI-matched females with normal glucose
      tolerance served as a control group. The diabetic patients were treated with
      cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was
      35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient.
      After one month of treatment with vitamin D3, the plasma 25(OH)D level increased
      by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS
      increased significantly by 34.3%, while the change in SPIS of 20.4% was not
      significant (p > 0.8). We found a significant correlation between the change in
      FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p <
      0.018). The results showed a decrease of 21.4% in insulin resistance after one
      month, but the change was not significant. Bearing in mind that the main defects
      in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the
      favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at
      least partly contribute to the impairment of insulin secretion and probably of
      insulin action. Our results suggest that vitamin D3 supplementation could be an
      element in the complex treatment of type 2 diabetes mellitus during the winter.

PMID- 12800454
TI  - Deficit in motor performance correlates with changed corticospinal excitability
      in patients with chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal
      pain, the severity of which is variable. Simple reaction times (SRTs) and
      movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to
      day changes in symptomatology with any change in SRT, SMT or corticospinal
      excitability. Ten CFS patients were tested on two occasions up to two years
      apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS)
      of the motor cortex were recorded from the thenar muscles. Threshold TMS strength
      to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs
      were measured. The percentage change in both SRTs and SMTs between the two test
      sessions correlated with the percentage change in corticospinal excitability
      assessed according to threshold TMS intensity required to produce MEPs. This
      study provides evidence that changing motor deficits in CFS have a
      neurophysiological basis. The slowness of SRTs supports the notion of a deficit
      in motor preparatory areas of the brain.

PMID- 12800455
TI  - Accuracy of intra-articular injections for osteoarthritis of the
      trapeziometacarpal joint.
AB  - A study was conducted to determine the accuracy of intra-articular injections for
      osteoarthritis (OA) of the trapeziometacarpal joint (TMCJ). Over a period of 12
      months intra-articular injections on 60 TMCJs (12 males and 48 females) were
      carried out. All the injections were performed in the operating theatre. The
      operator inserted the needle into the position clinically assessed to be the TMCJ
      and the position was assessed using biplanar fluoroscopy. In 42% of cases, the
      needle was incorrectly placed and its position had to be adjusted, using
      fluoroscopy, to ensure correct intra-articular placement. Entry into an
      osteoarthritic TMCJ with a blind passage of the needle is not straightforward. A
      proper injection technique must be employed to enter the correct joint. Using an
      image intensifier greatly facilitates accurate needle placement.

PMID- 12800456
TI  - Safety and effectiveness of replacing standard doxazosin with doxazosin in the
      gastrointestinal therapeutic system (GITS) formulation in elderly hypertensive
      patients.
AB  - The objective of this paper is to evaluate the safety and effectiveness of using
      doxazosin standard formulation in elderly hypertensive patients who were either
      uncontrolled or newly diagnosed, and replacing standard doxazosin with doxazosin
      in the gastrointestinal therapeutic system (GITS) formulation. We designed a
      postmarketing surveillance, open-label non-comparative, multicentre, clinical
      study covering primary care patients aged 65 years or older diagnosed with
      essential uncontrolled arterial hypertension. The study covered a period of 6-9
      months, divided into two phases. Phase I involved a minimum of three and maximum
      of six months in treatment with standard doxazosin; phase II began with the
      changeover from standard doxazosin to the GITS formulation and lasted 12 weeks.
      Of the 1705 patients initially enrolled, 1292 (75.8%) completed the study.
      Reduction in systolic blood pressure was 22.3 mmHg (13.7%) in phase I, and 3.9
      mmHg (2.77%) in phase II; reduction in diastolic blood pressure was 12.4 mmHg
      (13.2%) in phase I, and 2.4 mmHg (2.9%) in phase II. The percentage of controlled
      patients was 40.5% (691/1705) by the end of phase I and 45.3% (776/1705) by the
      end of phase II. A total of 154 patients suffered adverse events (AE), 127 during
      phase I and 27 in phase II. We conclude that doxazosin in its two formulations is
      effective and safe for the purpose of lowering blood pressure in elderly
      patients.

PMID- 12800457
TI  - Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ
      compared with losartan plus HCTZ in patients with essential hypertension.
AB  - Telmisartan, an angiotensin II receptor blocker, is an effective once-daily
      antihypertensive agent available either alone or in fixed-dose combination with
      hydrochlorothiazide (HCTZ). This multicentre, prospective, randomised, open
      label, blinded-endpoint (PROBE) study assessed the efficacy and safety of six
      weeks' treatment with telmisartan 40 mg/HCTZ 12.5 mg (n = 199) and telmisartan 80
      mg/HCTZ 12.5 mg (n = 200) versus losartan 50 mg/HCTZ 12.5 mg (n = 198) in
      patients with mild to moderate essential hypertension. During the last six hours
      of the dosing interval, telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ
      12.5 mg reduced mean ambulatory diastolic blood pressure (DBP) to a greater
      extent than losartan 50 mg/HCTZ 12.5 mg (treatment differences 1.8 mmHg [p <
      0.05] and 2.5 mmHg [p < 0.001], respectively). Telmisartan 80 mg/HCTZ 12.5 mg
      also lowered mean 24-hour DBP by 2.3 mmHg more than losartan 50 mg/HCTZ 12.5 mg
      (p < 0.001). Telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg
      produced greater reductions in ambulatory systolic blood pressure versus losartan
      50 mg/HCTZ 12.5 mg of 2.5 mmHg and 3.4 mmHg, respectively, during the last six
      hours of the dosing interval (p < 0.05), and of 2.1 mmHg and 3.4 mmHg,
      respectively, over the entire 24-hour dosing interval (p < 0.05). All treatments
      were well tolerated.

PMID- 12800458
TI  - Congenital coronary artery fistulas in Turkish patients undergoing diagnostic
      cardiac angiography.
AB  - A coronary artery fistula is a direct communication between a coronary artery and
      one of the cardiac chambers or vessels around the heart. The present study was
      undertaken to define the incidence, clinical findings and angiographic
      characteristics of congenital coronary artery fistula in Turkish adults who
      underwent diagnostic cardiac angiography. A consecutive series of 11,350 coronary
      angiography, performed between January 2000 and December 2001, was
      retrospectively examined for the presence of coronary artery fistulas. The
      incidence of congenital coronary artery fistulas was 0.08%. All the patients had
      chest pain during exertion or at rest. All the fistulas were single and most
      arose from the proximal left anterior descending coronary artery and drained into
      the pulmonary artery. All the fistulas were small. Surgical treatment was not
      indicated. A congenital coronary artery fistula in adults is a distinct though
      rare entity, variable in its incidence and commonly associated with coronary
      artery obstructive disease. Diagnosis is mostly incidental during routine
      coronary angiography.

PMID- 12800459
TI  - Sexual activity cardiological survey on members of the Israel Heart Society.
AB  - A nationwide telephone survey conducted under the auspices of the Israeli Heart
      Society examined cardiologists' knowledge of and attitudes towards sexual
      activity among cardiac patients with concomitant sexual dysfunction. The items
      covered demography, understanding of relevant mechanisms, drug effects and
      cardiovascular physiology during sexual activity, suitable interventions and
      sources of the cardiologists' knowledge. Compliance was excellent (364/379 [96%]
      responders). Attitudes and knowledge were similar among males and females: 74%
      underestimated the published frequency of erectile dysfunction in general and
      among cardiac patients specifically; 90% knew that beta-blockers cause erectile
      dysfunction but few responded correctly about other non-cardiac drugs; 77% try to
      cope with their patient's problematic sexual function, especially younger
      cardiologists who tended to be more up to date about it. Israeli cardiologists
      are motivated to assist these patients but demonstrate a general lack of adequate
      up to date knowledge on the epidemiological, physiological and pharmacological
      aspects of the problem.

PMID- 12800460
TI  - The design of venous thromboembolism prophylaxis trials: is enoxaparin more
      effective than fondaparinux?
AB  - The aim of thromboprophylaxis is to minimise the incidence of clinically relevant
      venous thromboembolism (VTE) but in many trials designed to determine the
      efficacy of thromboprophylactic agents, asymptomatic VTE is included in the
      primary endpoint. Since asymptomatic events occur much more frequently than
      symptomatic events, they dominate the results. Data from trials comparing the
      thromboprophylactic efficacy of enoxaparin and fondaparinux in orthopaedic
      surgical patients are used to demonstrate that asymptomatic and symptomatic
      endpoints may yield different conclusions. There was no difference between these
      agents in the incidence of symptomatic VTE. Efficacy and safety results of
      thromboprophylactic studies are affected by other aspects of trial design such as
      the dose of each agent and the timing of treatment initiation and endpoint
      assessment. Such factors should be considered when designing clinical trials and
      evaluating their results.

PMID- 12800461
TI  - Management of psychosis in Parkinson's disease.
AB  - Psychosis is one of the most disabling complications associated with Parkinson's
      disease (PD) and occurs in up to 30% of PD patients treated chronically with
      antiparkinsonian drugs. Visual hallucinations, with or without delirium and
      paranoid delusions, are the most frequent symptoms. Psychosis complicating PD can
      be more disabling than the motor symptoms of PD; it frequently poses a serious
      threat to the patient's ability to maintain independence and is the single
      greatest risk factor for nursing home placement. Choosing an antipsychotic drug
      for a PD patient is a common clinical dilemma. The conventional antipsychotic
      drugs are poorly tolerated in PD because of their predictable and at times
      profound worsening in parkinsonian motor symptoms. The recent availability of
      atypical antipsychotic drugs that can control psychotic symptoms without
      compromising motor function has led to significant advances in therapeutic
      strategies in the management of PD psychosis in the community. This article
      reviews data on the use of atypical antipsychotics in patients with PD and the
      current recommendations on their use in the management of PD psychosis.

PMID- 12800462
TI  - COX-LOX inhibition: current evidence for an emerging new therapy.
AB  - Safe and effective drug treatment is an important objective of all doctors. In
      the treatment of arthritis, non-steroidal anti-inflammatory drugs offer effective
      treatment but safety is significantly limited, largely due to gastrointestinal
      toxicity. Attention has recently focused on exploiting increased knowledge of
      metabolism of arachidonic acid to allow the development of safer anti
      inflammatory drugs. Dual inhibitors of cyclo-oxygenase and lipoxygenase are
      planned. These drugs may inhibit formation of both prostaglandins and
      leukotrienes. This review outlines the salient features of cyclo-oxygenase and
      lipoxygenase metabolism of arachidonic acid. The role of the eicosanoids in
      mediating inflammation and gastrointestinal integrity is delineated. Evidence is
      presented regarding action of licofelone, one COX/LOX inhibitor that is currently
      in advanced stages of clinical trials. This review examines the hypothesis that
      licofelone is an effective anti-inflammatory agent that does not cause peptic
      damage.

PMID- 12800463
TI  - Omega-3 fatty acids: their role in the prevention and treatment of
      atherosclerosis related risk factors and complications.
AB  - Fatty acids are an important source of energy which can have an influence on
      serum lipids. Omega-3 and omega-6 fatty acids, both polyunsaturated fatty acids,
      have been advocated as replacement for saturated fat. Omega-3 fatty acids,
      derived from fish and certain green plants, lower serum triglycerides, but they
      have also been shown to have a direct effect on myocardial contractility, blood
      pressure, platelet function, coagulation factors, cell-mediated immunity and
      markers of inflammation. Recently available clinical trial data, including those
      using the concentrated omega-3 fatty acid preparation Omacor, indicate that omega
      3 fatty acids are valuable in preventing sudden death following myocardial
      infarction. Studies indicate that omega-3 fatty acids are just as effective as,
      or have a benefit superior to, statins in secondary prevention. Omacor is also
      useful in the treatment of hypertriglyceridaemia, both as monotherapy and in
      combination with statins.

PMID- 12800464
TI  - Etoricoxib in the treatment of chronic pain.
AB  - For the many patients who suffer chronic pain, we seek the most effective anti
      inflammatory drug with the least side-effect profile and the greatest long-term
      safety. Etoricoxib, a selective COX2 inhibitor, has been shown to be as effective
      as non-selective non-steroidal anti-inflammatory drugs in the management of
      chronic pain in rheumatoid arthritis and osteoarthritis, for periods of up to one
      year. Data on etoricoxib efficacy in chronic low back pain is beginning to
      emerge. The side-effect profile of etoricoxib suggests it is well tolerated with
      similar adverse effects to non-selective NSAIDs. Larger studies are awaited, to
      see whether superior gastrointestinal tolerability can be proven. Further work
      will be required to show that etoricoxib is safe in patients with pre-existing
      cardiovascular or gastrointestinal comorbidity, and the potentially confounding
      role of aspirin still needs to be elucidated. However, etoricoxib shows promise
      as a new and effective COX2 inhibitor in clinical practice.

PMID- 12800465
TI  - Pimecrolimus: a review of pre-clinical and clinical data.
AB  - Pimecrolimus (Elidel) is a novel cell-selective inhibitor of inflammatory
      cytokines that has specifically been developed for the treatment of inflammatory
      skin diseases due to its favourable skin selective pharmacological profile.
      Therapeutic efficacy and safety of pimecrolimus cream 1% has been established in
      the short-term treatment and the long-term management of atopic eczema in
      clinical studies in adults, children and infants. It rapidly relieves pruritus,
      and redness and swelling disappear or are only mild in up to 70% of pimecrolimus
      treated patients during the first three weeks. When applied at the first signs
      and symptoms of atopic eczema, pimecrolimus has proven to prevent flare
      progression and to provide superior long-term disease control compared with a
      conventional treatment, based on reactive use of corticosteroids. Pimecrolimus
      cream 1% is well tolerated, even on sensitive areas such as the face and neck.
      Blood concentrations remain low, even when extensive body areas are treated and
      no clinically significant systemic effects have been observed during short- or
      long-term clinical studies with pimecrolimus.

PMID- 12800466
TI  - Small intestinal metastasis from renal cell carcinoma exhibiting rare findings.
AB  - Small intestinal metastasis from renal cell carcinoma (RCC) has only rarely been
      described. We report two patients who developed small bowel metastases from RCC
      showing different clinicopathological characteristics. Both patients underwent
      hemilateral nephrectomy for RCC and developed lung metastases metachronously or
      simultaneously. One patient developed occlusive ileus caused by multiple polypoid
      tumours composed of sarcomatoid tissue in the jejunum shortly after nephrectomy.
      The other patient presented melaena due to bleeding from a Borrmann 2-like tumour
      in the jejunum six years after nephrectomy. Clinically, his disease was slow
      growing. Sarcomatoid histology and Borrmann 2-like tumour in this report are rare
      findings in metastatic tumour of RCC in the small bowel.

PMID- 12800467
TI  - Relaparotomy: a five-year review of indications and outcome.
AB  - Complications from abdominal surgery may necessitate reoperation and can be
      associated with significant morbidity and mortality. This review aims to analyse
      the incidence and outcome of relaparotomy for various indications. In a
      retrospective review of case notes of patients who had undergone one or more
      relaparotomies during the same hospitalisation between 1996 and 2000, 55 patients
      required relaparotomy. Indications included bleeding, infection, anastomotic
      leakage, wound dehiscence, necrotising pancreatitis, bowel necrosis, bowel
      obstruction and miscellaneous indications. Relaparotomy for dehiscence and
      obstruction carried minimal risk; for bleeding and infection entailed moderate
      risks; and for anastomotic leak had the highest mortality rate. The mortality
      rate increased in older age groups, multiple system and organ failure and
      multiple relaparotomies. The overall mortality rate was 38%. Twenty-nine per cent
      of patients had MRSA infection contributing to sepsis and multiple system and
      organ failure. Reintervention had brought to evidence technical errors, which
      could be corrected, and resulted in patient salvage in some cases. The mortality
      rate of relaparotomy has remained unchanged compared with data published
      previously, despite improvements in surgical techniques and critical care. Timely
      relaparotomy is valuable in the identification and treatment of complications
      following abdominal surgery.

PMID- 12800468
TI  - 52nd Annual Scientific Session of the American College of Cardiology, Chicago,
      March 30-April 2, 2003.

PMID- 12800469
TI  - A yoga teacher with persistent cheilitis.
AB  - This is a depiction of an evolving case report right from its presentation to the
      physician and its documentation and further sharing of it through the net via e
      mails and evidence-based-health@jiscmail.ac.uk as well as other colleagues.

PMID- 12800470
TI  - Unusual perianal tumours masquerading as abscesses.
AB  - Tumours of the perianal region and anal canal are uncommon and can present in a
      variety of ways. Acute anorectal sepsis is a common condition that usually
      presents as a painful lump close to the anal margin. Tumours in the perianal
      region may mimic the symptoms and signs of anorectal sepsis, thereby leading to a
      delay in diagnosis and management. We report three patients who presented to our
      department with symptoms and signs suggestive of perianal abscess but which on
      further investigation were discovered to be due to unusual perianal tumours. Only
      one of the tumours was found to be malignant--a primary perianal mucinous
      adenocarcinoma; the other two were benign, a leiomyoma and an aggressive
      angiomyxoma. A high index of clinical suspicion is required to the diagnosis of
      perianal tumours when assessing patients with painful perianal lumps,
      particularly those with a long history and those of ethnic origin. Every effort
      should be made to establish a preoperative diagnosis so that correct treatment
      can be delivered.

PMID- 12800471
TI  - Palliative surgery for acute bowel obstruction caused by Kaposi's sarcoma in a
      patient with AIDS.
AB  - Patients with human immunodeficiency virus (HIV) infection or acquired immune
      deficiency syndrome (AIDS) can present with acute abdominal surgical problems,
      either with intra-abdominal opportunistic infection as a result of their
      immunosuppression, or with associated malignancies. We report a 39-year-old man
      who developed intermittent nausea and vomiting, which was originally thought to
      be a side-effect of the chemotherapy he was receiving for facial Kaposi's
      sarcoma. However, he was found to have intraperitoneal Kaposi's sarcoma causing
      small bowel obstruction, which was successfully excised at laparotomy. There were
      no perioperative complications despite AIDS-related respiratory disease. The
      patient remained free of abdominal symptoms until his death. HIV infections or
      AIDS alone should not be contraindications to surgery for such problems, as
      careful patient selection can yield good results and significantly improve
      quality of life.

PMID- 12800472
TI  - Atrial fibrillation storms.
AB  - Evolving pacemaker and device technology now allows the onset pattern of
      arrhythmias to be identified. It is recognised that some cardiac arrhythmias have
      a circadian pattern of onset and that ventricular arrhythmias can occur in
      clusters of electrical storms. The long-term follow-up of patients with an atrial
      defibrillator suggests that in some patients persistent atrial fibrillation
      recurrences are not random, but can occur in clusters of 'atrial fibrillation
      storms'. A case report is used to demonstrate this newly recognised phenomenon.

PMID- 12800473
TI  - Bone marrow metastasis in anaplastic oligodendroglioma.
AB  - Oligodendroglioma is a rare primary brain tumour. These tumours rarely metastasis
      extraneurally because of the absence of a lymphatic system, the presence of the
      blood-brain barrier and the patient's poor overall survival. Oligodendroglioma
      may spread via the cerebrospinal fluid or after surgical intervention. Metastasis
      to bone marrow is extremely rare. Oligodendroglioma is now considered a
      chemosensitive disease. If chemotherapy leads to prolonged survival, we may see
      more extraneural metastases in future.

PMID- 12800474
TI  - Testicular torsion: a twist to the tale.
AB  - Testicular torsion is a surgical emergency that requires prompt exploration if
      testicular viability is to be maintained. Although rare, it is essential to be
      aware that it may occur despite previous fixation (orchidopexy). Testicular
      torsion occurring after previous orchidopexy is rare, but recognition of this
      possibility is essential to prevent testicular infarction and subsequent
      orchidectomy. During scrotal exploration a wide variety of methods for
      orchidopexy exist. We present a case of testicular torsion despite previous
      fixation and discuss the merits of various techniques available for orchidopexy.

PMID- 12800475
TI  - Massive bleeding from an arteriovenous malformation in the gastric fundus
      following gastric biopsy treated by embolisation.
AB  - A 60-year-old male was admitted with massive upper gastrointestinal bleeding
      following a gastric biopsy. Repeat gastroduodenoscopy failed to identify the
      source. Angiography identified bleeding from an arteriovenous malformation at the
      fundus of the stomach. This was controlled by embolisation.

PMID- 12800476
TI  - Diabetic nephropathy.
AB  - As the epidemic of diabetes spreads so does the number of patients at risk for
      developing diabetic nephropathy, which occurs in 20% to 40% of all diabetic
      patients. Indeed, diabetes is the most common cause of end-stage renal disease
      (ESRD) in the United States, accounting for > 40% of patients starting renal
      replacement therapy each year. Unfortunately, the outcome for diabetic patients
      with ESRD is worse than that for nondiabetic patients because of comorbid
      conditions in the diabetic population. However, with early and intensive blood
      glucose and blood pressure control--including the use of angiotensin-converting
      enzyme inhibitors and angiotensin receptor blockers--the development and
      progression of diabetic kidney disease can be slowed.

PMID- 12800477
TI  - Diabetic retinopathy.
AB  - Diabetic retinopathy is the principal cause of irreversible blindness in patients
      of working age in the industrialized world (1,2). For some types of retinopathy
      (e.g., proliferative disease), effective treatment in the form of laser
      photocoagulation has been available for more than 20 years, but many patients
      seek help too late when treatment is no longer effective. Macular edema, which is
      much more common in patients with type 2 diabetes mellitus, may be the presenting
      sign and therefore may already be established at diagnosis. If vision is
      significantly reduced, current treatment options are often ineffective. Screening
      of diabetic persons for early signs of retinopathy, which are treatable, improves
      the visual prognosis. Medical factors such as good blood glucose control,
      management of hypertension, and regulation of blood lipid levels are also
      considered to be of major importance.

PMID- 12800478
TI  - Cardiovascular complications of diabetes: prevention and management.
AB  - Cardiovascular (CV) complications are by far the most prevalent in patients with
      type 2 diabetes and the principal cause of mortality. Renal complications of type
      1 diabetes were the principal cause of death. However, with the advent of
      dialysis and renal transplantation and because of further increases caused by
      such management techniques on the already accelerated atherosclerosis of type 1
      diabetes patients, CV complications have now become the principal cause of
      morbidity and mortality. For successful prevention of CV complications in
      diabetes, clinicians should therefore pay particular attention to the means of
      attaining goals for the management of established traditional as well as
      nontraditional CV risk factors. For the most part, such management has been
      proven to reduce CV events in patients with diabetes, particularly type 2
      diabetes.

PMID- 12800479
TI  - Management of neuropathy and foot problems in diabetic patients.
AB  - Diabetic neuropathy (DN) is a complex set of clinical syndromes that affect
      distinct regions of the nervous system, either singly or combined. DN is the most
      common form of neuropathy in the developed countries of the world and is
      responsible for 50% to 75% of nontraumatic amputations. It is also the most life
      damaging--once autonomic neuropathy sets in, the mortality rate approximates 25%
      to 50% within 5 to 10 years. Distal symmetric polyneuropathy, the most common
      form of DN, usually involves both small and large nerve fiber damage. Small nerve
      fiber neuropathies occur early and are often present without objective signs or
      electrophysiologic evidence of nerve damage. The greatest risk is foot ulceration
      and subsequent gangrene. Large nerve fiber neuropathies, which involve the
      sensory and motor nerves, are generally neuropathies of signs rather than
      symptoms. Clinical presentation usually includes a "glove and stocking"
      distribution of sensory loss and the greatest risk is Charcot's neuroarthropathy.
      Diagnosis of DN relies heavily on a careful patient history and physical
      examination. Most critical is that both the patient and the patient's shoes
      should be examined and corrective measures taken. Several studies have shown that
      good diabetes control can significantly reduce neuropathy. As new drugs and ways
      to enhance nerve blood flow and block pain pathways at different levels are being
      explored, the effective treatment of DN and the reduction of its impact on
      quality of life as well as mortality will become a reality. Patient education and
      preventive strategies, however, are still the best ways to treat the
      complications of neuropathy and reduce the amputation rate.

PMID- 12800480
TI  - Insulin therapy for the critically ill patient.
AB  - The risk of mortality or significant morbidity is high among critically ill
      patients who are treated in the intensive care unit (ICU) for > 5 days. These
      patients are susceptible to sepsis, excessive inflammation, critical illness
      polyneuropathy, and multiple organ failure, the latter often being the cause of
      death. Most intensive care patients, even those who did not previously suffer
      from diabetes, are hyperglycemic, which is presumed to reflect an adaptive
      development of insulin resistance. In the K.U. Leuven study it was hypothesized
      that hyperglycemia is not a beneficial adaptation to severe illness but rather
      predisposes patients to many of the typical intensive care complications-
      prolonged intensive care dependence and death. The effects of intensive insulin
      therapy to maintain normoglycemia during critical illness were studied in a large
      group (N = 1548) of ventilated, surgical ICU patients. An algorithm was proposed
      for implementing this procedure. The randomly assigned intensive insulin therapy
      group received insulin infusion tailored to control blood glucose (BG) levels in
      the range 80-110 mg/dL, whereas the conventional treatment group received insulin
      only when glucose levels exceeded 200 mg/dL, and in that event were maintained in
      a target range of 180-200 mg/dL. Intensive insulin therapy induced a 43%
      reduction of intensive care mortality risk (P = 0.036 after correction for
      interim analyses) and a 34% reduction of hospital mortality (P = 0.005). A
      reduced risk of severe infections by 46% (P = 0.003) was associated with a 35%
      reduction in prolonged (> 10 d) requirement for antibiotic therapy (P < 0.001).
      In addition, excessive inflammation was prevented. Logistic regression analysis
      indicated that control of BG levels, rather than insulin administration itself,
      likely explains the observed clinical benefits. Use of insulin infusion to
      maintain normoglycemia using a titration algorithm, at least in populations
      similar to those in the Leuven study, improves outcome. Further data are needed
      to establish the applicability of this strategy to other patient groups, such as
      those in a medical ICU and in general hospital care.

PMID- 12800481
TI  - [Evolution of Helmholtz theory on the basis of research of accommodation
      executive mechanisms].
AB  - The authors used a profound biochemical analysis of clinical observations in
      different spheres of ophthalmology as well as their own many-year observations of
      the biomechanical intraocular systems to describe the eye accommodation system. A
      defined and advanced Helmoholtz accommodation theory, which from now on does not
      contradict the laws of mechanics in all its phases, is offered. The principles of
      interrelated activities of the main and auxiliary accommodation executive
      mechanisms are described; they enabled an explanation for a number of actual
      observations, which were not understood, in the past, from the standpoint of
      incompleted but correct in its essence Helmholtz accommodation theory. A total
      classification of all accommodation executive mechanisms was worked out and
      presented by the authors.

PMID- 12800482
TI  - [Accommodation in the young age. Norm and pathology].
AB  - The review describes the main provisions of theories and understanding related
      with the physiology and pathology of accommodation from the time of Helmholtz up
      to the present-day; besides, methods of therapy and prophylaxis in accommodation
      disturbances in young people are summarized.

PMID- 12800483
TI  - [The role of immunopathological reactions in the development of eye diseases in
      persons infected by hepatitis B virus and the efficiency of immuno-correcting
      therapy].
AB  - The role of immunologic factors in the development of ophthalmic pathologies in
      persons infected by hepatitis B virus (HBV) affecting the liver or in
      asymptomatic virus carriers (a total of 285 persons, 328 eyes) was studied. The
      deficit of CD3 and CD4 cells, gammopathy, increased levels of circulating immune
      complexes and of TNF-alpha in the serum; the deficit of IgA and an enhanced
      secretion of IgG in the lachrymal fluid; as well as a weakened ability of the
      local and systematic production of IFN-alpha were typical for a majority of
      patients. The most profound changes were detected in cases of uveitis; apart from
      the above mentioned, an increase of the CD4/CD8 index as well as of organ
      specific and inter-organ immunization was found. The cases of keratitis (92% of
      the stromal type) were distinguished through a hypersecretion of TNF-alpha both
      in the serum and in the lachrymal fluid. Complicated cataracts were observed
      mainly in convalescents or in asymptomatic virus carriers; immune disorders were
      less seldom encountered in this category, as compared to the cases of eye
      inflammations, and basically they were local. The obtained data were considered
      in treatment. Imunofan, when added to the traditional therapy (symptomatic and
      corticosteroid one), activated the local and systematic antiviral immunity,
      suppressed the production of pro-viral cytokines and reduced the autoimmune
      reactions. As a result of this, the treatment time, the frequency rate of
      relapses as well as the number of anti-inflammatory and postoperative (in
      cataracts) complications decreased. The study results are indicative of that the
      immunopathological reactions, which are typical of HBV patients, can be detected
      at the ocular level and they can provoke ophthalmic pathologies. The nature,
      severity and relation between the local and systematic immune disorders
      predetermine, to a considerable extent, the development of an eye disease and its
      severity. The treatment (and prophylaxis) of HBV-associated ophthalmic
      pathologies require an obligatory usage of immunity-correcting means and clinical
      and-immunological monitoring.

PMID- 12800484
TI  - [Diagnosis and importance of the opportunistic herpes-virus infection in etiology
      and pathogenesis of different eye diseases].
AB  - A total of 439 patients (adults--184, children--255) with herpetic keratitis as
      well as with uveitis and choriorenitis of different geneses and localizations
      were examined. An aggravation of HSV-infection was determined by detecting, in
      the blood), anti-bodies to the unstructured early viral antigens by using the
      immune enzyme analysis (IEA). The efficiency of the test was demonstrated during
      the examination of patients with different ophthalmic pathologies. An active
      infection was detected in 16-39% of patients with various ocular diseases of non
      herpetic etiology. The pathogenetic value of reactivated HSV infection is
      diverse: it can function as an etiological or trigger factor and it can aggravate
      the main disease through causing, postoperatively, complications.

PMID- 12800485
TI  - [The state-of-the art and prospects for the pharmacological therapy of infectious
      and allergic eye diseases].
AB  - The inflammatory, infectious and allergic diseases of the eye still remain an
      acute problem in practical ophthalmology due to their high prevalence, relapsing
      clinical course, a growing frequency rate of mycotic and acanthoamebic keratitis
      and a growing number of resistant causative agents of bacterial keratitis. 55.3%
      of corneal pathologies are related with the herpes simplex virus, 37.3%--with
      secondary bacterial infection, 33.2%--with primary bacterial infection, 6.7%-
      with mycotic infection and 5.6%--with acathoamebic infection. Algorithms of
      pharmacological therapy are suggested for a majority of inflammatory lesions of
      the eye, i.e. for herpetic keratitis, ulcerous keratitis caused by blue pus
      bacillus, gonococcus, staphylococcus, fungi, acanthomebas, as well as for
      adenoviral and Chlamidia conjunctivitis and allergy of the eye. The author points
      out that the treatment must be complex, including specific therapy--antiviral one
      (zovirax ointment, interferon locally, and zovirax or valtrex perorally),
      antibacterial one (okacin, tobrex, vitabact, fucithamic locally, quinine
      antibiotics perorally, aminoglycosides or cephalosporins subconjunctivally or
      intramuscularly) and antimycotic one (locally and perorally). Another part of the
      complex therapy is equally important--pathogenetic one (carnosine, taufon,
      vitacic, corneregel ointment), antiallergic one (spersallerg, allergophtal,
      alomide, lecrolin), antinflammatory one (naclof, maxidex, cyclolip) tears
      replacing one (natural tears, ophthagel) and immunomodeling one (affinoleicin,
      lycopid, tactivin).

PMID- 12800486
TI  - [Disorders in the immune regulation and hemostasis as factors triggering the
      proliferative retinopathy in diabetes mellitus].
AB  - A comprehensive clinical- immunological- and-hemostasiological study of the
      lachrymal fluid and blood of 105 patients with diabetic retinopathy (DR) showed
      that an "extreme" activity of the local antibody-dependent response to collagens,
      DNA, cytokine, TNF-alpha, increased levels of the circulating immune complexes
      (CIC) and of antibodies to DNA in the blood serum as well as local immune
      insufficiency and deficiency of free antibodies to collagens and TNF-alpha in the
      lachrymal fluid and serum during the onset of proliferative forms and traction
      retinal detachment are the key manifestations of the immune pathology in a
      progressing DR. Signs of hypercoagulation, free heparin deficiency, a reduced
      activity of fibrinolysis and insufficiency of the anti-thrombin system were
      detected with the development of the chronic syndrome of disseminated
      intravascular blood coagulation. Trends of the immunohemostatic correction of the
      activity of the local and systemic autoimmune responses and of hemostasis were
      substantiated during the generally accepted therapy of diabetes mellitus and of
      systemic micro- and-macroangiopathy.

PMID- 12800487
TI  - [Psychophysical and electrophysiological tests in diagnosis of the early sign of
      glaucomatous optic neuropathy].
AB  - Visual field losses and changes of the optic nerve disk are signs of optic
      neuropathy in glaucoma; psychophysical and electrophysiological tests can
      contribute to an early detection of glaucomatous optic neuropathy.
      Electrophysiological methods, like pattern electroretinogram (PERG) and visual
      induced cortical potentials can be useful in the diagnosis of glaucoma since they
      are compatible with the functions of retinal ganglion cells. A combination of
      psychophysical and electrophysiological examination methods contribute to an
      early diagnosis of glaucoma because they make it possible to study different
      aspects of visual functions. The results of psychophysical tests correlate to a
      greater extent than electrophysiological tests with defects in visual fields.
      Temporal, temporal-and-spatial contrast sensitivity and visual induced cortical
      potentials, whose changes are detected in the "preperimetric" stage of glaucoma,
      are the most sensitive parameters, while PERG changes later. Both the color
      contrast and light PERGs reduce in glaucoma. However, a significant correlation
      was detected only between the reduction of the color contrast PERG and visual
      field defects. A reduced sensitivity of dark and color channels of the retinal
      cone systems was also registered. Defects of color sensitivity are more
      pronounced and they precede the onset of light sensitivity changes. Defects of
      color and contrast sensitivity are an early sign of the progressing of optic
      neuropathy in glaucoma.

PMID- 12800488
TI  - [Retinal ischemia and nitric oxide].
AB  - Retinal ischemia is the main chain in the pathogenesis of vascular diseases of
      the eye. It was established that nitric oxide (NO) plays the key role in the
      development of ischemia. Recent understanding of the NO role, as a universal
      regulator of the cellular and tissue metabolism, is presented. The authors' and
      published data were used to design a scheme of pathogenesis of retinal ischemia
      with regard for the NO role. NO can produce both positive and negative effects
      depending on a stage of the process, NO concentration and on a number of other
      factors if they are present. Initial stages of hypoxia/ischemia are accompanied
      by an activation of all forms of NO-synthases (NOS) caused by the influence of
      biologically active substances (cytokines, prostaglandins, serotonin, bradykinin,
      glycolisis suboxide products etc.). The activation of inducible NOS, which
      synthesize a bigger quantity of NO possessing a direct cytotoxic action and
      contributing to the production of highly toxic radical of peroxinitrit, is in the
      focus of attention. The damage of cellular structures due to free-radical
      processes leads to the development of endothelial, macrophage and thrombocyte
      malfunctions, which manifest itself through a reduced activity of endothelial NOS
      and through disruption of NO-dependent processes (vasospasm, an increased
      aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction
      of NO synthesis substrate (L-arginine) is observed in patients with retinal
      ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an
      exhaustion of L-arginine and its intensified consumption in the course of free
      radical processes. The use of NO-inhibitors and of NO-donors at different stages
      of retinal ischemia prevents the development of neovascularization and
      proliferation.

PMID- 12800489
TI  - [An experimental substantiation of nitric-oxide containing gas flow in the
      treatment of eye traumas].
AB  - The hypothesis on the biostimulating effect of exogenous nitric oxide (NO) was
      made use of to develop a new method to stimulate the healing of wounds through
      treating them by a NO saturated gas flow. The above gas flow is generated by air
      plasma unit "Plazon". The experimental and clinical studies confirmed that the NO
      therapy is a highly effective treatment method for different lesions of the skin
      and soft tissues. We tried to use the above method in ophthalmology. A
      comprehensive experimental study was carried out to assess the impact of the NO
      containing gas flow on the eyeball structures. An optimal mode was designed,
      which does not exert any influence on the intraocular pressure, Ph of the
      lachrymal fluid, antioxidative activity and on the proteinase-inhibitor balance
      in tears; no morphological changes occurred in the ocular tissue structures. The
      mentioned morphological and biochemical studies confirmed that the application of
      the NO-containing gas flow speeds up the healing, process of both an experimental
      cornea erosion and penetrating corneal wounds. Optimal modes of NO-therapy were
      defined for both types of lesions.

PMID- 12800490
TI  - [Modern understanding of the pathogenesis of pre-proliferative diabetic
      retinopathy].
AB  - Diabetic retinopathy (DR) is a severe and late complication of diabetes mellitus
      leading, in a majority of cases, to poor vision and blindness. The pathogenesis
      of DR and of the main diseases is complicated; many of its chains are not
      explained until now. Hyperglycemia is the key reason of many metabolic disorders
      in diabetes mellitus resulting in vascular complications. An irreversible
      glycosylation of proteins and activation of free-radical lipid peroxidation occur
      under the conditions of a long-term hyperglycemia; it brings about structural
      changes in the retinal microvessel walls, disorders of hematoretinal barrier and
      transcapillary metabolism as well as hemodynamic and vasoocclusive changes
      provoking the development of retinal ischemia.

PMID- 12800491
TI  - [Electroretinography in the diagnosis and study of pathogenesis of X-linkage
      retinoschizis].
AB  - Due to an extensive variability of manifestations of X-linkage retinoschizis,
      there is a need in a differential diagnosis of it and of other hereditary retinal
      diseases. The method of electroretinography is often of primary importance in
      specifying a diagnosis in ophthalmology; it both enables the detection of new and
      more sensitive criteria of early and differential diagnosis and ensures a more
      profound understanding of changes occurring in the retina. A topical analysis of
      changes of the bioelectric activity taking place in different retinal layers and
      sections as well as a differential evaluation of the functional condition of
      neurons and glia Muller's cells in patients with X-linkage retinoschizis were
      accomplished within the framework of this study. The nature of the peak latency
      and of the b-wave amplitude in the electroretinogram (ERG) and in the mechano
      electroretinogram (MERG) as well as of a low-frequency ERG is indicative of that
      Muller's cells are damaged; the damage severity is related with an intensity of
      the pathological process and can be objectively determined by the ERG
      examinations of patients. An analysis of sub-components of a low-frequency
      rheoelectroretinogram (RERG) shows weakened inhibitory inter-neuron connections
      in the retina, which is a sign of disease aggravation. The regularities of
      changes of retinal biopotential to blue light flashes under all registration
      conditions (ganz-feld, macular and rhythmical stimulation) differ from the ERG
      dynamics to other light stimuli, which is indicative of a significant role of the
      pathology of S-cone paths in the development of X-linkage retinoschizis.

PMID- 12800492
TI  - [Recent aspects of pathogenesis and treatment of endocrine ophthalmopathy].
AB  - Many-year observations of 925 patients with endocrinous ophthalmopathy (EO) as
      well as the instrumental and morphological examinations of biopsy materials
      showed that EO is not an independent disease--it is provoked by malfunction of
      the thyroid gland as a result of complicated immunopathological interactions. A
      possibility of euthyroid EO is proven. Optimal methods of corticosteroid therapy,
      possibilities of radiotherapy and the role of surgical interventions in different
      EO stages are described.

PMID- 12800494
TI  - The Escherichia fergusonii iucABCD iutA genes are located within a larger
      chromosomal region similar to pathogenicity Islands.
AB  - Three strains of Escherichia fergusonii (EF873, EF1496, EF939) of 50 strains
      tested produced the hydroxamate siderophore aerobactin. Screening of a cosmid
      library of the strain EF873 chromosomal DNA (in aerobactin nonproducing
      Escherichia coli VCS257) for aerobactin production identified iucABCD and iutA
      gene orthologues. The predicted IucABCD and IutA proteins showed 59-65% identity
      to the corresponding proteins of Shigella flexneri and E. coli. Aerobactin
      molecules synthesized by E. fergusonii and E. coli strains stimulated growth of
      aerobactin indicator strains harboring either E. coli or E. fergusonii iutA
      genes. In the 12 kb upstream and 17 kb downstream regions of the iuc and iut
      genes, 20 additional ORFs were identified. Their gene products showed homology to
      proteins from E. coli, S. flexneri, Klebsiella aerogenes, Pseudomonas aeruginosa
      and Vibrio cholerae. Probes recognizing DNA sequences from a region of more than
      25 kb, which included the iucABCD and iutA genes, hybridized with chromosomal DNA
      of two aerobactin-producing strains (EF873 and EF939), but not with other
      nonproducing E. fergusonii strains tested. These data, together with the genetic
      organization of this region, suggest that E. fergusonii iucABCD iutA genes are a
      portion of a larger segment of DNA similar to pathogenicity islands of other
      bacteria.

PMID- 12800495
TI  - Glutathione metabolism of Acremonium chrysogenum in relation to cephalosporin C
      production: is gamma-glutamyltransferase in the center?
AB  - Methionine increased the intracellular glutathione (reduced) (GSH) pool and the
      specific gamma-glutamyltransferase (gamma-GT) activity in the cephalosporin C
      (CPC) producer Acremonium chrysogenum. The accelerated turnover of GSH might be
      indicative of the existence of a functioning gamma-glutamate cycle, and might
      supply the CPC biosynthetic machinery with L-cysteine. The gamma-GT was not
      subject to nitrogen metabolic repression but was more active in cells exposed to
      different oxidative-stress-generating agents. Exogenous cysteine hindered both
      the uptake of methionine and the induction of gamma-GT, and was not beneficial
      for CPC production. There was no causal relationship between the redox status of
      the cells and the observed cell morphology.

PMID- 12800493
TI  - Mammalian antibiotic peptides.
AB  - The increasing development of bacterial resistance to traditional antibiotics has
      reached alarming levels, thus creating a strong need to develop new antimicrobial
      agents. These new antibiotics should possess novel mechanisms of action and
      different cellular targets compared with existing antimicrobials. Recent
      discoveries and isolations of so-called animal antibiotics, mostly small cationic
      peptides, which represent a potent branch of natural immunity, offered the
      possibility to acquire new and effective antibiotics of this provenance. To this
      date, more than 500 antibiotic peptides have been distinguished and defined.
      Their antimicrobial properties present new opportunities for their use as
      antibiotics or for construction of their more effective derivatives, but much
      research is still required to pave the way to their practical use. This is a
      survey of substances forming an armamentarium of natural immunity of mammals.

PMID- 12800496
TI  - Bacteriocin diversity in Bacillus sphaericus.
AB  - Nondenaturing polyacrylamide gel electrophoresis revealed the presence of
      diversity among bacteriocins produced by strains of Bacillus sphaericus.
      Bacteriocin bands of six strains (pathogenic and non pathogenic) were found to be
      located just below the stacking gel. However, in two other strains (1 pathogenic
      and 1 collection strain) more than one protein band with bacteriocin activity
      were seen in the middle of resolving gel. In bacteriocin-treated cultures,
      electron-microscopy studies revealed the growth of lysedswollen ghost cells, and
      loss of viability among sensitive strains.

PMID- 12800497
TI  - Heterogeneity of Escherichia coli derived from artiodactyla animals analyzed with
      the use of rep-PCR fingerprinting.
AB  - Genetic polymorphism of 83 isolates of E. coli, derived from 4 species of
      artiodactyla animals living in a relatively close contact on the grounds of a
      theme park ZOO Safarii Swierkocin (Poland) was determined using the rep-PCR
      fingerprinting method, which utilizes oligonucleotide primers matching
      interspersed repetitive DNA sequences in PCR reaction to yield DNA fingerprints
      of individual bacterial isolates based on repetitive extragenic palindrome (REP)
      primers. The fingerprint patterns demonstrated the essential polymorphism of
      distribution of REP sequences in genomes of the examined isolates. The arithmetic
      averages clustering algorithm (UPGMA) statistical analysis of fingerprints with
      the use of the Jaccard similarity coefficient differentiated E. coli isolates
      into three similarity groups containing various numbers of isolates. The groups
      comprised isolates derived from two, three and four species of the source
      animals. The isolates derived from each source segregated in the dendrogram in a
      different way, both within the similarity groups and among them, indicating an
      individual repertoire of E. coli in the examined species of animals. The
      similarity relations among E. coli derived from the same source, illustrated in a
      dendrogram with a number of subclusters of a low mutual similarity (< or = 20%),
      indicated an essential interstrain differentiation in terms of the distribution
      of REP sequences. Our results confirmed the hypothesis of the oligoclonal
      characters of populations obtained from particular sources. The rep-PCR
      fingerprinting method with REP primers is simple and highly differentiating and
      can be recommended for use in explorations of large groups of animals and
      monitoring the variability of strains.

PMID- 12800498
TI  - Purification and partial characterization of alpha-L-arabinofuranosidase produced
      by Thermomonospora fusca.
AB  - Thermomonospora fusca produced a relatively high level of alpha-L
      arabinofuranosidase when growing on oat spelt xylan as the main carbon and energy
      source. The enzyme exhibited maximum relative activity (0.136 U/g protein) at pH
      9.0 with 54 and 55% activity remaining at pH of 4.5 and 11.0, respectively. The
      apparent Km value for the crude alpha-L-arabinofuranosidase preparation was 180
      mumol/L 4-nitrophenyl alpha-L-arabinofuranoside; the upsilon lim value was the
      release of 40 mumol/L 4-nitrophenol per min. Enzyme activity was eluted as a
      single peak (HPLC gel filtration chromatography) corresponding to molar mass of
      approximately 92 kDa. Native electrophoresis of crude cell lysate confirmed the
      presence of a single active intracellular alpha-L-arabinofuranosidase component.
      SDS-PAGE of this enzyme, developed as zymogram, did not demonstrate any activity;
      denaturing gel was stained and a protein band of relative molar mass of 46 kDa
      was revealed. Isoelectric focusing of a purified alpha-L-arabinofuranosidase
      yielded a single protein band for the corresponding activity zone with pI 7.9.
      The enzyme was purified approximately 21-fold the mean overall yield was about
      16%.

PMID- 12800499
TI  - Effects of alkali metal ions on some virulence traits of Candida albicans.
AB  - The effects of the alkali metal ions (Li+, Na+ and K+) on the growth and on
      certain virulence factors (adhesion, cell-surface hydrophobicity and germinating
      ability) of Candida albicans were determined. High concentrations of these ions
      displayed an inhibitory effect on the growth of the Candida cells; preincubation
      in their presence showed a negative effect on all virulence factors studied. The
      changes induced during the preincubation remained there even when high
      concentration of the ions was removed from the cell suspension. In contrast, a
      considerable growth was found at high Na+ and K+ concentrations. Although alkali
      metal ions significantly decreased certain virulence traits of the fungus they
      did not totally inhibit adhesion and germ-tube formation. This suggests that C.
      albicans may represent a health hazard even at a high salt concentration.

PMID- 12800500
TI  - Colocalization of cortical microtubules and F-actin in Dipodascus magnusii using
      confocal laser scanning microscopy.
AB  - Distribution of microtubules and F-actin in aerobically growing cells of
      Dipodascus magnusii, belonging to the class Saccharomycetes was analyzed using
      immunofluorescence microscopy and labeling with rhodamine-tagged phalloidin. A
      conspicuous system of permanent cytoplasmic microtubules was observed in
      association with multiple nuclei. In elongating cells, helices of cytoplasmic
      microtubules appeared at the cell cortex. In cells approaching cytokinesis
      transversely oriented microtubules were revealed at incipient division sites.
      Confocal laser scanning microscopy showed a continuity of these transverse
      microtubules with the remaining microtubule network. The actin system of D.
      magnusii consisted of patches and filaments. Patches were found to accumulate at
      the tips of growing cells. Bands of fine actin filaments were usually observed
      before F-actin rings were established. A close cortical association of
      microtubules with the F-actin ring was documented on individual optical sections
      of labeled cells. Cells with developing septa showed medial F-actin discs
      associated at both sides with microtubules. Colocalization of cytoplasmic
      microtubules with actin filaments at the cortex of dividing cells supports a role
      of both cytoskeletal components in controlling cell wall growth and septum
      formation in D. magnusii.

PMID- 12800501
TI  - Monitoring the growth and stress responses of yeast cells by two-dimensional
      fluorescence spectroscopy: first results.
AB  - S. cerevisiae growth and responses to different treatments were monitored by two
      dimensional fluorescence spectroscopy, which simultaneously detects the
      fluorescence of a number of cells' own fluorophores. Growth curves of cultures of
      free cells were measured by means of tryptophan fluorescence in nonfluorescent
      culture medium and a flow-through system at a suitable excitation/emission beam
      geometry. Fast responses of the cells to anaerobic-aerobic transition or addition
      of glucose, methanol or cyanide, which could not be measured in this system
      because of the time delay inherent in transporting the cells from the culture
      flask to the cuvette, were monitored with cells immobilized in alginate. The
      major fluorescence changes caused by these treatments belonged to NAD(P)H which
      is a good indicator of the redox state of the cells.

PMID- 12800502
TI  - Trehalose, glycogen and ethanol metabolism in the gcr1 mutant of Saccharomyces
      cerevisiae.
AB  - Since Gcr1p is pivotal in controlling the transcription of glycolytic enzymes and
      trehalose metabolism seems to be one of the control points of glycolysis, we
      examined trehalose and glycogen synthesis in response to 2% glucose pulse during
      batch growth in gcr1 (glucose regulation-1) mutant lacking fully functional
      glycolytic pathway and in the wild-type strain. An increase in both trehalose and
      glycogen stores was observed 1 and 2 h after the pulse followed by a steady
      decrease in both the wild-type and the gcr1 mutant. The accumulation was faster
      while the following degradation was slower in gcr1 cells compared to wild-type
      ones. Although there was no distinct glucose consumption in the mutant cells it
      seemed that the glucose repression mechanism is similar in gcr1 mutant and in
      wild-type strain at least with respect to trehalose and glycogen metabolism.

PMID- 12800503
TI  - Passing of fluorescein derivatives into the hyphae of Phanerochaete
      chrysosporium.
AB  - Fluorescein derivatives added into the growth medium were decolorized during
      submerged cultivation of Phanerochaete chrysosporium. The highest decrease of
      absorbance A450 was observed in the growth phase regardless of the presence of
      inducers Tween 80 or poly(ethylene glycol) (PEG). Fluorescein linked to PEG was
      prepared and, after addition to cultures, shown to stimulate the production of
      lignin peroxidase. Passing of fluorescing substances into hyphae (observed by
      confocal microscopy) showed that they were concentrated on some structures inside
      hyphae.

PMID- 12800504
TI  - Characterization of Candida albicans colony-morphology mutants and their hybrids.
AB  - The collection wild-type strain of Candida albicans was used to obtain
      auxotrophic and colony-morphology mutants by 'nitrosoguanidine' treatment.
      Intraspecific protoplast fusion induced by Ca(2+)-poly(ethyleneglycol) was
      carried out in various pairings between the auxotrophic strain producing smooth
      colonies and containing blastospores and the colony-morphology mutants containing
      a mixture of blastospores and pseudohyphae or only hyphae. Hybrids exhibiting
      full or partial complementation were obtained when mutants producing smooth
      colonies and colony-morphology variants of different origins were fused. The
      mutation responsible for the colony-morphology character (if various types of
      colony morphomutants were crossed) proved to be recessive or semidominant.
      Representative hybrids exhibited elevated DNA contents as measured by flow
      cytometry. To illustrate various cell types, and especially the intermediate one
      (never observed in natural isolates), a preparation method was further developed
      for scanning electron microscopic studies.

PMID- 12800505
TI  - Physiological characterization of osmotolerant yeast Pichia sorbitophila and
      comparison with a putative synonym Pichia farinosa.
AB  - The osmotolerant yeast Pichia sorbitophila was found to differ from other yeast
      species, not only from the conventional ones (Saccharomyces cerevisiae,
      Schizosaccharomyces pombe), but also from those widely known as osmotolerant
      (Debaryomyces hansenii, Zygosaccharomyces rouxii). P. sorbitophila was able to
      survive extremely high extracellular concentrations of salts (e.g., saturated
      solution of KCl) and other osmolytes (70% glucitol), although it is not
      classified as halophilic (or osmophilic). P. sorbitophila assimilated a broad
      range of carbon and nitrogen sources with extreme effectiveness. On solid media,
      P. sorbitophila created colonies of variable shapes and sizes in relation to
      media composition, number of colonies on the plate and cultivation conditions.
      Colonies were able to produce long-distance signals between each other that
      resulted in growth inhibition of the facing parts of both colonies, but were not
      inhibited by colonies of other yeast species growing on the same plate. Though
      sometimes P. sorbitophila has been indicated as a synonym of P. farinosa,
      comparative physiological studies together with PCR amplification of P. farinosa
      DNA fragments homologous to known P. sorbitophila genes provided a strong
      indication that this strain should be classified as a separate species.

PMID- 12800506
TI  - Viability of basidiomycete strains after cryopreservation: comparison of two
      different freezing protocols.
AB  - The viability of 250 basidiomycete strains was determined after a 2-d and then
      after a 2-year storage under liquid nitrogen using two different freezing
      protocols. Using an original agar plug protocol (OP), 162 strains (65%) of the
      250 strains survived a 2-d storage and 158 strains (63%) survived a 2-year
      storage in liquid nitrogen. Using a straw protocol (CP), 246 strains (98%) of the
      250 strains survived a 2-d storage and 243 strains (97%) a 2-year storage in
      liquid nitrogen. In addition, other 106 strains were newly estimated using the CP
      protocol; 104 (98%) of them survived successfully a 2-d storage and 101 (95%) of
      them survived a 2-year storage in liquid nitrogen. The results indicate that the
      protocol used for cryopreservation can significantly influence strain survival.
      Markedly better results were obtained using the CP protocol.

PMID- 12800507
TI  - Isolation of Arcobacter butzleri and A. cryaerophilus in samples of meats and
      from meat-processing plants by a culture technique and detection by PCR.
AB  - A pilot survey of sources of contamination with arcobacters (representing a
      potential risk for humans) was done in a wide range of samples involved various
      kinds of meat (beef, pork, meat products, chilled chickens, etc.) from a retail
      level and domestic farming. Sanitary practices in slaughterhouses and production
      lines were checked in two different plants (a beef and pork production and a
      chicken processing plant). The method is based on a selective enrichment to
      isolate suspect strains, in combination with a PCR technique specific for
      arcobacters. The choice of a suitable enrichment broth and a plating agar was
      made with the use of pure bacterial strains and by means of real meat samples
      seeded with Arcobacter butzleri. The PCR technique was optimized to allow
      differentiation of a 1223 bp product, typical of the genus Arcobacter, and a
      product of 686 bp, specific for A. butzleri a total number of 198 samples were
      tested, of that 33 (17%) were found to be positive for the genus Arcobacter but
      only 22 (11%) for A. butzleri.

PMID- 12800508
TI  - Primers ITS1, ITS2 and ITS4 detect the intraspecies variability in the internal
      transcribed spacers and 5.8S rRNA gene region in clinical isolates of fungi.
AB  - Restriction fragment length polymorphism analysis of the 5.8S rRNA gene and the
      internal transcribed spacers (ITS1 and ITS2) was used for examination of 66
      isolates belonging to 19 species. Intraspecies variability was found in the
      examined region of 11 species (Candida albicans, C. catenulata, C. colliculosa,
      C. glabrata, C. kefyr, C. melinii, C. parapsilosis, C. guillermondii, C. solanii,
      C. tropicalis, Saccharomyces cerevisiae). Region of ITS-5.8S rDNA was amplified
      using the primers ITS1 and ITS4. The amplicons were digested by HaeIII, HinfI and
      CfoI. The recognized intraspecies variability was confirmed in the second step,
      in which the shorter fragments of this region were amplified using primers ITS1
      and ITS2 and analyzed by capillary electrophoresis. Considerable intraspecific
      variability renders this method unsuitable for species identification, whereas it
      can be useful for epidemiological tracing of isolates.

PMID- 12800509
TI  - Detection of HLA-G on human extravillous cytotrophoblast and skeletal muscle with
      a new monoclonal antibody MEM-G/1.
AB  - Using immunohistochemistry with the newly available monoclonal antibody MEM-G/1
      the reaction patterns on frozen and formaldehyde-fixed paraffin-embedded sections
      on human placentas, lymph nodes, skeletal muscles, and kidney and liver
      allografts were compared. HLA-G (a nonclassical major histocompatibility complex
      class I molecule that is assumed to influence the immune response during
      pregnancy and some pathological conditions) was found within human extravillous
      cytotrophoblast but not within villous cytotrophoblast and placental mesenchymal
      tissue. No HLA-G expression on human lymph nodes, tonsils, and kidney and liver
      allografts was demonstrated. However, HLA-G expression was observed in all
      samples of skeletal muscle. The binding capacity of monoclonal antibody MEM-G/1
      provides new possibilities to study physiological and pathophysiological roles of
      HLA-G in humans.

PMID- 12800510
TI  - Occurrence of extended-spectrum beta-lactamases among Escherichia coli isolates
      from hospitalized and healthy children.
AB  - The prevalence of extended-spectrum beta-lactamases (ESBL) was determined among
      isolates of Escherichia coli (n = 63) isolated from hospitalized (43) and healthy
      (20) children. Ten isolates (21%) were ESBL-positive for two screening tests, the
      double disk-synergy test and the Oxoid Combination Disk method. One ESBL-positive
      isolate came from a healthy child. The transfer frequency of oxyimino-beta-lactam
      resistance from ESBL-producing isolates to E. coli K12 C600 recipient strain
      ranged from 10(-8) to 10(-5) per donor cell. Donor strains and transconjugants
      displayed susceptibility patterns typical of ESBL producers. They were resistant
      to oxyimino-beta-lactams but susceptible to clavulanic acid and carbapenems.
      Seven out of the 10 ESBL-positive isolates were found to produce MR/MS fimbria,
      which may play an important role in the colonization of the human intestinal
      mucosa.

PMID- 12800511
TI  - Effect of vaccination therapy for acne, using a staphylococci antigenic complex
      in combination with clindamycin.
AB  - A group of 46 patients with acne vulgaris were prescribed clindamycin in
      combination with a vaccination therapy using a staphylococci antigenic complex
      (Polystafana; Sevapharma, Czechia). Acne papulopustulosa was diagnosed in 36
      patients and acne indurata in 10 patients. The clinical effect of clindamycin and
      Polystafana was determined on the basis of the regression of the inflammatory
      manifestation of acne: regression by 0-30% was considered unsuccessful, by 30-80%
      satisfactory, and above 80% excellent; the immunomodulation effect of the
      treatment was evaluated in parallel. The clinical effect was excellent in 21
      patients with acne papulopustulosa and in 6 with acne indurata; it was
      accompanied by pronounced immunomodulation effect as both cellular and humoral
      immunity was also tended to return to normal values. A satisfactory clinical
      effect was observed in 15 patients with acne papulopustulosa, whose cellular
      immunity component was also stimulated. Only 4 patients with acne indurata failed
      to respond successfully. These were the patients who showed a pronounced deficit
      of the cellular immunity component persisting even after the treatment. The
      administration of clindamycin in combination with Polystafana vaccination can be
      recommended as an effective means for the treatment of acne vulgaris.

PMID- 12800512
TI  - Effects of soil pH, temperature and water content on the growth of Burkholderia
      pseudomallei.
AB  - Optimum conditions were determined for the growth of Burkholderia pseudomallei in
      natural soils or waters. It grows better in paddy soil, crop-covered and fallow
      field than in fresh and salty water. Although the optimal temperature and pH for
      the growth were 37 or 42 degrees C, and 6.5 or 7.5 in an environmental-mimicking
      soil medium, this bacterium can still grow at 4 degrees C, which was suggested to
      be related with the occurrence of melioidosis in some cold areas. In soil media
      with water content < 15. B. pseudomallei did not grow until 60 d of incubation,
      suggesting that water contents of soils in which it dwelled would be one
      important factor in determining the growth rate.

PMID- 12800513
TI  - Colicinogeny in local isolates of salmonellae and plasmid transfer studies.
AB  - Colicinogeny was determined in local isolates of S. typhimurium and S.
      enteritidis. Fourteen out of 35 S. typhimurium isolates of hospital origin were
      colicin producers whereas only one chicken isolate out of 82 S. enteritidis
      isolates of various origin (human, chicken or egg) produced colicin. A colicin
      producing, cephalothin (Cpt)- and piperacillin (Prl)-resistant local isolate of
      Salmonella havana (H32) harbored 4 plasmids of 54.0, 28.4, 2.7 and 1.9 kb. Upon
      curing its plasmids, the strain lost the ability to produce colicin and
      resistance to antibiotics and no longer expressed smooth lipopolysaccharide
      (LPS). The outer membrane protein (OMP) of 34.6 kDa was also lost. Using
      nalidixic acid (Nal)-resistant mutant of the cured strain in conjugation
      experiments, 10 out of 27 transconjugants were found to be resistant to Nal and
      Prl, 10 were resistant to Nal and Cpt and 7 showed Nal, Prl and Cpt resistance.
      Cpt and Prl resistance were determined by 54.0 and 28.4 kb plasmids,
      respectively. There was no direct correlation between plasmid contents and
      colicinogeny, LPS and OMP profiles.

PMID- 12800514
TI  - Characterization of Cryptococcus neoformans var. neoformans serotype A and A/D in
      samples from Egypt.
AB  - The cryptococcal polysaccharide antigen was detected in 10 cerebrospinal fluid
      (CSF) and 23 serum samples from cryptococcal meningitis and intestinal
      cryptococcosis by the cryptococcal antigen latex agglutination system (CALAS).
      CALAS titers in CSF and serum samples of cryptococcal meningitis ranged over 8
      2048 and 32-2048, respectively, while in cases of intestinal cryptococcosis,
      serum titers ranged over 8-2048. The isolates of yeast Cryptococcus neoformans
      were determined to be of serotype A or of the A/D pair. The total leukocyte count
      and biochemical parameters in CSF were significantly increased as indicators of
      microbial infection. Furthermore, the in vitro change of the teleomorph (sexual
      state) to the anamorph (asexual state) was also detected and the teleomorph state
      changed in vivo to the encapsulated anamoph state which is more virulent during
      infection in vivo than the yeast-like noncapsulated form. Two primers for
      internal transcribed spacer (ITS) regions of ribosomal DNA were used for
      molecular detection of C. neoformans. After PCR amplification, a DNA band of 415
      bp, visualized on agarose gel, indicated the presence of C. neoformans cells in
      the tested CSF and serum samples. The primer sensitivity was also characterized
      using purified yeast chromosomal DNA as template; it was about 20 pg or more
      chromosomal DNA which represents about 10 cells of C. neoformans. The primers
      were also specific for ITS regions of C. neoformans and gave negative results
      with Candida albicans and E. coli chromosomal DNA templates.

PMID- 12800515
TI  - The PrP genotype of sheep of the improved Valachian breed.
AB  - In a worldwide majority of sheep breeds an excessive susceptibility to scrapie
      associated with the PrP gene alleles coding for valine (V; at the 136 codon) and
      glutamine (Q; at the 171 codon) (e.g., VRQ/VRQ, VRQ/ARQ, or ARQ/ARQ) was
      demonstrated. Particularly the PrPVRQ allele is closely associated with the high
      risk development of the disease; the PrPARQ allele can also fulfill this function
      but under certain limited conditions. Polymorphism in the PrP gene sequences
      (conclusively related to the increased susceptibility of sheep to scrapie) of
      improved Valachian sheep from two Slovak regions, Orava and Spis, was determined.
      Examination of 735 sheep showed that ARR/ARQ was the most frequent genotype
      (45.2%). High-risk genotypes were determined in 32.4% of sheep (ARQ/ARQ 19.3,
      ARR/VRQ 9.0, ARR/VRQ 3.5, VRQ/VRQ 0.3, ARR/VRR 0.3). Low-risk genotypes were
      found in 67.7% of sheep (ARR/ARQ 45.2, ARR/ARR 10.9, ARR/AHQ 5.7, ARQ/ARQ 4.9,
      AHQ/AHQ 0.7, ARR/AHR 0.3). Despite the geographically distant flocks of improved
      Valachian sheep investigated no difference in the occurrence of individual PrP
      genotypes was observed.

PMID- 12800516
TI  - Spreading of Salmonella enteritidis in the cecum of chickens.
AB  - Adhesion and colonization of high (2 x 10(8) CFU) and low doses (2 x 10(2) CFU)
      of Salmonella enteritidis (phage type 4) was determined in the ceca collected 6 h
      4 weeks after inoculation (pi), of 1-d-old White Plymouth Rock orally-inoculated
      chickens. S. enteritidis was associated with the epithelial surface of the villi
      in the low-dose group 18 h-7 d pi, the penetration in the cecal lamina propria
      was observed on day 1 and 10 pi. In the high-dose group, adhesion and
      colonization was observed in all birds killed 6 h-14 d pi; penetration of the
      bacteria into the cecal lamina propria was seen 1-21 d pi. Large numbers of
      macrophage-like cells containing S. enteritidis were observed in the cecal lamina
      propria on days 3-21 pi. Colonization and migration by S. enteritidis in the
      intestinal tract of chickens was shown to be dose dependent.

PMID- 12800518
TI  - How will the UK cope with an influx of EU nurses?

PMID- 12800517
TI  - The early postnatal development of salivary antibody and immunoglobulin response
      in children orally colonized with a nonpathogenic, probiotic strain of E. coli.
AB  - The development of levels of secretory immunoglobulins (SIgs) in newborns' saliva
      was examined under physiological conditions and after artificial colonization
      with nonpathogenic, probiotic bacterial strain E. coli O83. Higher levels of
      secretory immunoglobulin M (SIgM) and secretory immunoglobulin A (SIgA) were
      detected in the saliva of breast-fed children when compared with those of bottle
      fed infants. SIgM was found earlier than SIgA, the levels of both SIgM and SIgA
      decreased after weaning. Breastfeeding actively stimulates local immunity on
      mucosal membranes of newborn infants. Early mucosal colonization with
      nonpathogenic E. coli bacteria stimulates the mucosal immune system to produce
      specific antibodies as well as nonspecific secretory immunoglobulins.

PMID- 12800519
TI  - Are nurses picking up doctors' unwanted tasks?

PMID- 12800520
TI  - Cannabis smoking is for dopes--not for nurses.

PMID- 12800521
TI  - Changing specialty.

PMID- 12800522
TI  - How nurses can develop good patient information leaflets.
AB  - Nurses are increasingly involved in the development of patient information
      leaflets. Producing good patient information is a team effort between
      professionals and patients. Involve your patients, set clear goals and provide
      the very best information. Present the information as clearly and positively as
      possible. This article outlines the importance of a clear purpose, good
      information and accessible language. Guidance on how to achieve these things is
      provided, along with tips for improving the readability of your document. Details
      of online resources and training are also included.

PMID- 12800524
TI  - Urinary tract infections in women.

PMID- 12800523
TI  - What you need to know about ... osteoporosis.

PMID- 12800525
TI  - Compartment syndrome: the importance of early diagnosis.
AB  - Compartment syndrome is an acute orthopaedic emergency with a variety of causes,
      the most common following trauma to the limbs. Necrosis of muscle, nerve and skin
      tissue may result owing to oxygen deprivation. Early detection and appropriate
      treatment are essential if irreversible damage is to be avoided.

PMID- 12800526
TI  - Developing an interdisciplinary integrated continence service.
AB  - This article describes how one NHS trust transformed its fragmented continence
      services into a fully integrated interdisciplinary service across primary and
      secondary care. The service provides nurse-led first-line continence care to
      patients across a range of settings, avoiding inappropriate referrals and
      reducing waiting times for medical appointments. This was achieved by
      capitalizing on organisational changes, following government guidelines and
      adopting a process of systematic change. Developing services within existing
      resources and facilitating interdisciplinary collaboration requires creativity,
      clinical/organizational credibility and knowledge.

PMID- 12800527
TI  - Through the keyhole.

PMID- 12800528
TI  - Taking eye care to the patient.

PMID- 12800529
TI  - Skeletal pin traction: guidelines on postoperative care and support.
AB  - Orthopaedic pins and wires have been used to apply skeletal traction for many
      years, and there has been an increase in the use of external fixators (Santy,
      2000; Sims and Saleh, 2000). Multiple pins are frequently used and, as such,
      create potential portals for infection. Infection rates for these pins are
      reported to be as high as 85 per cent (Sims and Saleh, 2000). However, pin-site
      management practices are diverse, contradictory and lack consistency.

PMID- 12800530
TI  - Telemedicine and the law.
AB  - Every scientific development brings legal issues and cases in its wake. It is in
      the nature of scientific progress that there is usually a long gap before there
      is legal provision for the problems that arise. This article explores the legal
      implications of the use of telemedicine in wound management and highlights some
      of the issues that practitioners should be aware of when they are exploiting
      scientific developments in this field.

PMID- 12800531
TI  - The management of fluid leakage in grossly oedematous legs.
AB  - Oedema occurs when there is an abnormal amount of fluid in the interstitial
      space. Normally about 85 per cent of the fluid that is filtered out of
      capillaries into this space is reabsorbed; the rest is drained by the lymphatic
      system (Tortora and Grabowski, 2000). A rise in capillary blood pressure causes
      increased quantities of fluid to escape from capillaries. As a result, filtration
      of fluid into the tissues exceeds the reabsorption rate of fluid into the
      circulation, leading to oedema (Tortora and Grabowski, 2000) (Fig 1).

PMID- 12800532
TI  - The benefits of using hydrocolloids.
AB  - Hydrocolloids are interactive dressings that absorb fluids, and when this happens
      the physical state of the dressing changes to form a gel. Hydrocolloids contain
      carboxymethyl cellulose and a range of other polymers, which vary between brands.
      They are suitable for use on necrotic, sloughy, granulating and epithelializing
      wounds. Health professionals should consult individual manufacturers'
      instructions before using hydrocolloids on infected wounds.

PMID- 12800533
TI  - A step-by-step guide to classifying and managing pretibial injuries.
AB  - The pretibial region is a common site for soft-tissue injury in older people. A
      poor blood supply to the shin and co-morbidity in this group of patients leads to
      significant injury as a result of relatively minor trauma (Wood and Lees, 1994).

PMID- 12800534
TI  - Management of surgically hypogonadal patients unable to take sex hormone
      replacement therapy.
AB  - Lifestyle changes in diet, exercise and the environment may help to prevent or
      ameliorate hot flashes and low bone density in men and women after surgical
      castration. Conventional medications, including megestrol acetate, SSRIs or
      clonidine, may improve hot flashes but may have limiting side effects. Some
      complementary and alternative approaches, including black cohosh, vitamin E, and
      soy products, work as well as placebo to decrease hot flashes and may be helpful,
      because they have low toxicity. Acupuncture and neurontin are promising but must
      be studied further. With regards to the prevention of osteoporosis and fractures
      in men and women, bisphosphonates are the most potent of the currently available
      agents; calcitonin is less effective. PTH has a large beneficial effect but is
      not yet available and is less well studied. In women, continued sexual
      intercourse and use of vaginal lubricants and moisturizers help to minimize
      symptoms of vaginal atrophy but do not ameliorate urinary symptoms. Low dose
      local estrogen treatment is a promising approach for the latter complaints.

PMID- 12800535
TI  - Timing and special concerns regarding endocrine surgery during pregnancy.
AB  - Pregnancy may occur in the setting of endocrine diseases or be the first time
      these diseases manifest clinically. Management of pregnancy in these
      circumstances is challenging and requires a high degree of vigilance on the part
      of the treating physicians. The best outcome is achieved by a multidisciplinary
      approach consisting of endocrinology, obstetrics, anesthesiology, and endocrine
      surgery.

PMID- 12800536
TI  - Perioperative management of patients undergoing pituitary surgery.
AB  - The management of a patient who requires pituitary surgery should be a constant
      collaboration between the neurosurgeon and the endocrinologist. Because the
      pituitary gland is an anatomic and functional entity, both medical specialties
      are necessary to treat these patients for the best possible outcome. The notion
      that pituitary surgery is always curative is not accurate because of the risk for
      tumor recurrence. A patient with a pituitary lesion who undergoes surgery is
      clinically identical to a patient with diabetes mellitus--these patients require
      lifelong monitoring and management as indicated by the clinical, endocrine and
      anatomic findings. Because there is always a risk for tumor recurrence,
      appropriate surgical or radiation treatment and hormone replacement may be
      required at any time after the initial operation. In the patient who undergoes
      postoperative pituitary radiation, the risk for developing a new pituitary
      hormone deficiency ranges from 33% to 50%, and is probably higher over time.
      Thus, these patients must receive regular evaluations regarding the need for
      additional treatment and hormone replacements. A regular program of life long
      assessment of pituitary function and anatomy, appropriate hormone replacement and
      close collaboration with a pituitary surgeon is the ideal care of these patients.
      Only with such a program can a patient with a pituitary adenoma achieve the best
      possible outcome.

PMID- 12800537
TI  - Perioperative management of patients treated with glucocorticoids.
AB  - HPA suppression is a common consequence of glucocorticoid therapy, whereas overt
      secondary adrenal insufficiency is a rare but life-threatening condition.
      Prolonged hypotension and a response to adequate doses of a glucocorticoid agent
      are not reliable ways to assess adrenocortical function. One must also
      demonstrate plasma cortisol levels that are inappropriately low for the clinical
      situation. Hypotension in patients previously treated with glucocorticoids is
      caused by loss of the permissive effect of glucocorticoids on vascular tone,
      which may be related in turn to enhanced PGI2 production in the absence of
      glucocorticoids. It is not caused by mineralocorticoid deficiency. Recurrent
      problems of study design and interpretation have plagued this area of
      investigation. Any patient who has received a glucocorticoid in doses equivalent
      to at least 20 mg a day of prednisone for more than 5 days is at risk for HPA
      suppression. If the doses are closer to but above the physiologic range, 1 month
      is probably the minimal interval. Recovery from prolonged exposure to high doses
      of glucocorticoids may take up to 1 year. Pituitary function returns before
      adrenocortical function. Recovery from short courses of treatment (e.g., 5 days)
      occurs more rapidly, in about 5 days. Recovery is time-dependent and spontaneous.
      The rate of recovery is a function of the dose and duration of therapy before
      tapering is started and while the dose is being reduced. ACTH therapy does not
      cause adrenocortical suppression but offers no advantage over glucocorticoids,
      has several disadvantages, and should no longer be used. Patients on alternate
      day glucocorticoid therapy have some suppression of basal cortisol levels but
      have normal or nearly normal responses to provocative tests of adrenocortical
      function. The standard short ACTH stimulation test is a reliable means of
      assessing adrenocortical function preoperatively. The low dose (1 microgram)
      short ACTH test is promising but has not been sufficiently well characterized,
      requires serial dilutions and cannot be recommended at this time. Studies of the
      physiologic adrenocortical response to surgical stress provide a basis for
      revised dose recommendations for perioperative coverage in the patient with known
      or suspected HPA suppression. Recommendations of a multidisciplinary group are
      presented.

PMID- 12800538
TI  - Endocrine evaluation of patients with critical illness.
AB  - Prolonged critical illness has a high morbidity and mortality. The acute and
      chronic phases of critical illness are associated with distinct endocrine
      alterations. The acute neuroendocrine response to critical illness involves an
      activated anterior pituitary function. In prolonged critical illness, however, a
      reduced pulsatile secretion of anterior pituitary hormones and the so-called
      "wasting syndrome" occur. The impaired pulsatile secretion of GH, thyrotropin and
      gonadotropin can be re-amplified by relevant combinations of releasing factors,
      which also substantially increase circulating levels of IGF-1, GH-dependent
      IGFBPs, thyroxin, tri-iodothyronine and testosterone. Anabolism is clearly re
      initiated at the time GH secretagogues, thyrotropin-releasing hormone and
      gonadotropin-releasing hormone are coadministered but the effect on survival
      remains unknown. A lethal outcome of critical illness is predicted by a high
      serum concentration of IGFBP-1, pointing to impaired insulin effect rather than
      pituitary function, and survival was recently shown to be dramatically improved
      by strict normalization of glycemia with exogenous insulin. In addition to the
      illness-induced endocrine alterations, patients may have pre-existing central or
      peripheral endocrine diseases, either previously diagnosed or unknown. Hence,
      endocrine function testing in a critically ill patient represents a major
      challenge and the issue of treatment remains controversial. The recent progress
      in knowledge of the neuroendocrine response to critical illness and its
      interrelation with peripheral hormonal and metabolic alterations during stress,
      allows for potential new therapeutic perspectives to safely reverse the wasting
      syndrome and improve survival.

PMID- 12800539
TI  - Perioperative management of type 1 diabetes mellitus.
AB  - Clearly, perioperative management of diabetic patients requires thorough
      preoperative evaluation and planning whenever possible. A firm understanding of
      the pathophysiology of type 1 diabetes mellitus, the metabolic stress response,
      and the interactions between various forms of insulin and other variables such as
      supplemental nutrition and glucocorticoids can greatly assist in achieving a
      positive outcome. Consultation with an endocrinologist, internist, or other
      primary care provider comfortable with managing type 1 diabetes patients is
      strongly recommended to assist in the details of in-patient care and overseeing
      of proper ancillary support. It may also be helpful to allow the patient to
      function as an active decision-maker in the coordination of care, especially
      because a large percentage of type 1 diabetes patients (particularly those who
      are on insulin pumps) are well-educated about their disease process and their own
      physiologic idiosyncrasies. This knowledge can save valuable time and effort
      toward achieving the ultimate united goal of avoiding perioperative morbidity and
      mortality by maximizing glycemic control.

PMID- 12800540
TI  - Management of the bariatric surgery patient.
AB  - Morbid obesity has reached epidemic proportions in the United States.
      Unfortunately, medical interventions have been largely ineffective in this
      growing population. Currently bariatric surgery is the most effective
      intervention in managing morbid obesity and its comorbidities. As more patients
      become eligible for and pursue weight reduction surgery, it becomes important for
      the clinician to possess a thorough understanding of the different procedures
      available and the management of patients before, during, and after these
      surgeries. Significant weight loss and improvement in weight-related
      comorbidities are possible, with the best results available to the well-informed
      patient whose care is provided by a dedicated multidisciplinary team.

PMID- 12800541
TI  - Evaluation and management of hypo-osmolality in hospitalized patients.
AB  - Hyponatremia is the most common electrolyte disorder encountered in the clinical
      setting. Abnormalities of the mechanisms that maintain normal water and sodium
      metabolism are often present in hospitalized patients, including defects in renal
      water excretion. All of the current therapeutic approaches in patients with the
      syndrome of inappropriate antidiuretic hormone secretion and other forms of
      vasopressin-induced hyponatremia have significant limitations. Studies in animal
      models and humans have demonstrated that antagonists of the AVP V2 receptor in
      the kidney are effective in correcting hyponatremia. These new agents have been
      termed "aquaretics" because of their ability to induce a free water diuresis
      without the natriuresis or kaliuresis characteristic of diuretic drugs. When
      approved for clinical use, selective V2, and possibly also combined V1 + V2
      receptor antagonists will be helpful in therapy.

PMID- 12800542
TI  - Prevention, evaluation, and management of complications following thyroidectomy
      for thyroid carcinoma.
AB  - The rate of complications during thyroid surgery has decreased because of better
      instrumentation, illumination, and surgical expertise. Despite these
      improvements, certain patients, those requiring reoperation, those with invasive
      cancers or with numerous nodal metastasis or recurrent tumors, and those with
      large substernal goiters have a low but appreciable risk for complications. When
      planning a thyroid operation, one should perform the operation that corrects
      these problems and decreases the risk for complications. Localization of at least
      one parathyroid gland is essential. No surgical procedure can be done, however,
      without a risk of complications. To decrease these possible risks the surgeon
      should understand the embryologic development of the thyroid and parathyroid
      glands, the anatomical position of key structures, and use meticulous operative
      technique. Experience in performing thyroid operations is essential for the best
      outcome with the fewest complications.

PMID- 12800543
TI  - Perioperative management of patients with hypothyroidism.
AB  - Hypothyroidism is a common disorder affecting the cardiovascular, respiratory,
      hematopoietic, and renal organ systems--each of which is particularly germane in
      the management of the surgical patient. In general, treatment of recognized
      hypothyroidism is recommended before any surgical procedure whenever possible and
      euthyroidism should be documented by measurement of serum TSH as part of the
      preoperative evaluation. Such a strategy is likely to result in better surgical
      outcomes with improved morbidity and mortality. One exception to treating first
      with thyroid hormone is the patient with angina or coronary artery disease
      requiring bypass grafting, angioplasty or stenting. In this setting, preoperative
      thyroid hormone therapy could tax the ischemic myocardium. The coronary blood
      flow should be addressed first, and thyroid hormone therapy initiated afterwards.
      The authors have emphasized the need for caution in the interpretation of low
      serum thyroid hormones in sick or surgical patients because of the importance of
      distinguishing between hypothyroidism and the "euthyroid sick syndrome." There is
      no clear evidence at this point to support thyroid hormone replacement in the
      latter patients, and it may be potentially harmful. Rather, we hold that T3
      treatment of various surgical and other patients with nonthyroidal illness should
      be deferred until proof of its therapeutic efficacy is demonstrated.

PMID- 12800544
TI  - Perioperative management of the thyrotoxic patient.
AB  - Preoperative thyrotoxicosis is a potentially life-threatening condition that
      requires medical intervention before surgery. Most patients are undergoing
      thyroidectomy for persistent thyrotoxicosis, usually Graves' disease, either
      having contraindications to or failing medical therapy. Fewer patients are
      undergoing nonthyroidal surgery that is likely urgent or emergent. The choice of
      treatment depends on the time available for preoperative preparation, the
      severity of the thyrotoxicosis, and the impact of any current or previous
      therapies. Generally treatment is directed at a combination of targets in the
      thyroid hormone synthetic, secretory, and peripheral pathway with concurrent
      treatment to correct any decompensation of normal homeostatic mechanisms.
      Thionamides are the preferred initial treatment unless contraindicated, but do
      require several weeks to render a patient euthyroid. beta-Blockers should always
      be used unless absolutely contraindicated because they improve thyrotoxic
      symptoms especially of the cardiovascular system. Other agents including iodine
      and steroids can be used if rapid preparation is required or more severe
      thyrotoxicosis is present. The goal of therapy is to render the patient as close
      as possible to clinical and biochemical euthyroidism before surgery. Overall, the
      morbidity and mortality of adequately prepared patients is low.

PMID- 12800545
TI  - [Depression and schizophrenia].
AB  - Affective disorders in schizophrenia overlap with positive symptoms and are co
      morbid with negative changes. At schizophrenia onset, depression may emerge in
      the form of psychogenic disorders (posttraumatic stress disorder, juvenile
      asthenic failure, etc.). Depression, developing during the disease, determines
      clinical picture of attacks provoked psychogenically (hysterical depression,
      anxious depression)--reactive schizophrenia. In post-attack stages of
      schizophrenia, two types may be singled out--post-psychotic depression and post
      schizophrenic one. The post-psychotic depressions us includes neuroleptic
      depression with features of anesthetic melancholia, persevering depression,
      akinetic depression, neuroleptic dysphoria. Its induced by antipsychotics and
      combine with extrapyramidal disorders.

PMID- 12800546
TI  - [Neuromyalgic syndrome in children's infections].
AB  - Neuromyalgic syndrome (NMS) is clinically and electroneuromyographically (ENMG)
      first-ever described in 50 children aged 2-13. Muscular pains and pains along
      peripheral nerves occur in post-infection period of acute respiratory viral
      infections (ARVI), intestinal and parotitoviral infections with transient (in 3-6
      days), dysfunction of peripheral nervous system and muscles. NMS is characterized
      by predominant involvement of lower limb muscles in pathologic process and by
      rarely developing generalized form. There are 3 types of changes of nerve
      conductivity and excitability with conductive blocks absence and disturbances
      regression that enable to distinguish these dysfunctions from ENMG changes in
      polyneuropathy. Provoked by infection, transitory non-specific inflammatory
      muscular reaction and functional disorders of nerve conductivity and excitability
      may be considered as one of the possible mechanisms of NMS development. More than
      20 years of clinical and research experience of in neuroinfections clinic,
      supports the validity of NMS distinguishing among children acute infections for
      further diagnostic differentiation with polyneuropathy, viral meningitis and
      ARVI.

PMID- 12800547
TI  - [Pathogenesis of main objective neurological symptoms in Chiari malformation type
      I].
AB  - To study the influence of Chiari malformation (CM) size, patient's age,
      hydrocephaly and intracranial hypertension on the disease manifestations, 263
      patients with CM type I without concomitant syringomyelia have been examined. All
      the patients underwent clinical neurological examination, craniography and
      magnetic resonance imaging of the brain and spinal cord. Five main groups of
      objective neurological signs were identified: oculomotor (17.1%); cochlear
      vestibulocerebellar (84.8%); bulbar (35.4%); conduction motor (25.9%); segmental
      motor sensory disturbances (9.5%). The data obtained suggest that (1) a complex
      of pathogenic factors determines clinical manifestations of the disease in the
      given patient with CM type I; (2) CM size determines significantly the incidence
      and extent of the main objective neurological signs; (3) with age the seventy of
      cochlear and vestibulocerebellar disturbances increases; (4) hydrocephaly and
      intracranial hypertension deteriorate cochlear, vestibulocerebellar and bulbar
      disturbances as well as pyramidal-tract signs.

PMID- 12800548
TI  - [Psychiatric, psychological, and neurological characteristics of patients with
      chronic low back pain].
AB  - We examined 143 patients, aged 18-65 years, with chronic low back pain, in 78 of
      patients diagnosed as chronic somatoform pain disorder (CSPD)--ICD-10 F45.4--and
      in 65 as chronic pain syndrome (CPS) caused by spine pathology (M48.0, M51.1,
      M54.4). Depressive symptoms predominated in CSPD patients, who exhibited more
      pronounced psychopathological disturbances and two-fold higher frequency of
      personality disorders, comparing to those with CPS. In CSPD patients pain
      severity and reaction to pain syndrome were significantly higher than in CPS
      patients. Psychodiagnostic study revealed higher expressed anxiety and depression
      as well as socio-psychological maladaptation in CSPD patients as compared to CPS
      ones. After neurological examination, significant between-group differences were
      found in the frequency of muscular-tonic myofacial, syndrome and iliosacral joint
      dysfunction.

PMID- 12800549
TI  - [Use of biofeedback in combined treatment of low spine pain].
AB  - One hundred and six patients with dorsalgia of lumbar-sacral spine have been
      examined and treated. The developed and tested optimal methodology for using
      biofeedback, reflex therapy and manual therapy in a combined treatment of
      patients of different age in acute and chronic stages of the disease raised
      treatment efficacy. Combined treatment, including biofeedback, manual therapy,
      acupuncture of patients with dorsalgia, provides rapid arrest of pain syndrome,
      reduction of high tonicity of paravertebral muscles, motion volume increasing in
      lumbar spine region. Biofeedback allows patients to self-regulate muscle tone,
      therefore prevent further possible exacerbations.

PMID- 12800550
TI  - [Crisis of computer diagnosis and ways of its overcoming].
AB  - Despite a widespread application of computer technologies in medicine, there is
      currently a lack of diagnostic computer programs, meeting neurological needs.
      Most of the existing programs depend on some subjective factors. The authors
      propose their own computer program named "indicated diagnosis", and demonstrate
      its potential for diagnosis of peripheral monoparesis. Indicated diagnosis
      included testing and structuring of clinical and anatomical traits, along with
      the data of instrumental examination of the patients, ranging from patients
      complaints to establishing topic and nosologic diagnosis. Indicated diagnostics
      algorithm may be used for measuring of the lesions of nerves, plexuses, terminals
      and spinal cord segments involved in limb innervation.

PMID- 12800551
TI  - [Insufficiency of nigrostriatal dopaminergic system as a disregulation mechanism
      of dopamine-dependent depression syndrome].
AB  - Considered here, is a role of insufficiency of central dopaminergic systems in
      the pathogenesis of depression. Experimental data have been obtained in a rat
      model of depression-like syndrome caused by administration of specific-for
      dopamine-neurons neurotoxin 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine. Along
      with literature data, these results suggest a reduction of dopaminergic system
      activity in striatum, accompanied by the latter's hyperactivation, as a
      pathophysiological mechanism for development of certain depressive disorders.

PMID- 12800553
TI  - [The role of neuronal migration anomalies in the genesis of disneuroontogenic
      children disorders].

PMID- 12800552
TI  - [Acute pharmacological extrapyramidal disturbances].

PMID- 12800554
TI  - [Modern conceptions of alcohol encephalopathy pathogenesis].

PMID- 12800555
TI  - Create and sustain a healthy work environment.

PMID- 12800556
TI  - HIPAA at the eleventh hour: do you know where your imaging center is?

PMID- 12800557
TI  - Staffing and the "invisible hand".

PMID- 12800558
TI  - How to get a consultant before a consultant gets you.

PMID- 12800559
TI  - Strengthening your ties to referring physicians through RIS/PACS integration.
AB  - Many imaging centers are turning to technology solutions to increase refering
      physician satisfaction, implementing such enhancements as automated report
      distribution, picture archiving and communications system (PACS), radiology
      information systems (RIS), and web-based results access. However, without
      seamless integration, these technology investments don't address the challenge at
      its core: convenient and reliable, two-way communication and interaction with
      referring physicians. In an integrated RIS/PACS solution, patient tracking in the
      RIS and PACS study status are logged and available to users. The time of the
      patient's registration at the imaging center, the exam start and completion time,
      the patient's departure time from the imaging center, and results status are all
      tracked and logged. An integrated RIS/PACS solution provides additional support
      to the radiologist, a critical factor that can improve the turnaround time of
      results to referring physicians. The RIS/PACS enhances the interpretation by
      providing the patient's history, which gives the radiologist additional insight
      and decreases the likelihood of missing a diagnostic element. In a tightly
      integrated RIS/PACS solution, results information is more complete. Physicians
      can view reports with associated images selected by the radiologist. They will
      also have full order information and complete imaging history including prior
      reports and images. Referring physicians can access and view images and exam
      notes at the same time that the radiologist is interpreting the exam. Without the
      benefit of an integrated RIS/PACS system, the referring physician would have to
      wait for the signed transcription to be released. In a seamlessly integrated
      solution, film-tracking modules within the RIS are fused with digital imaging
      workflow in the PACS. Users can see at a glance if a historical exam is available
      on film and benefit when a complete study history--both film-based and digital-
      is presented with the current case. It is up to the imaging center to market the
      benefits of reduced errors, reduced turnaround times, and a higher level of
      service to referring physician community, and encourage them to take advantage of
      the convenience it provides. The savvy imaging center will also regard the
      integrated RIS/PACS as a valuable marketing tool for use in attracting
      radiologists.

PMID- 12800560
TI  - Strategic planning for radiology: opening an outpatient diagnostic imaging
      center.
AB  - Launching a new diagnostic imaging center involves very specific requirements and
      roadmaps, including five major areas of change that have a direct impact on
      planning: Imaging and communication technology Finances and reimbursement
      Ownership structure of imaging entities Critical workforce shortages Imaging is
      moving outside radiology First, planning must focus on the strategic level of any
      organization, whether it is a multi-national corporation or a six-person
      radiology group. Think of all organizations as a triangle with three horizontal
      levels: strategic, managerial and operational. The strategic level of decision
      making is at the top of the triangle, and here is where planning must take place.
      For strategic planning to work, there must be focused time and energy spent on
      this activity, usually away from the reading room and imaging center. There are
      five planning strategies, which must have the explicit goal of developing and
      growing the imaging center. The five strategies are: Clinical and quality issues,
      Governance and administration, Technology, Relationships, Marketing and business
      development. The best way to plan and implement these strategies is to create
      work groups of radiologists, technologists, and administrative and support staff.
      Once the group agrees on the strategy and tactic, it takes responsibility for
      implementation. Embarking on the launch of a new outpatient diagnostic imaging
      center is no small undertaking, and anyone who has struggled with such an
      endeavor can readily attest to the associated challenges and benefits. Success
      depends on many things, and one of the most important factors relates to the
      amount of time and the quality of effort spent on strategic planning at the
      outset. Neglecting or skimping on this phase may lead to unforeseen obstacles
      that could potentially derail the project.

PMID- 12800561
TI  - A tale of two CRs: hospital conducts side-by-side test.
AB  - While we elected to install a digital radiography system in the busiest exam room
      in emergency room (ER) suite at our 535-bed hospital, we selected computed
      radiography as the primary platform for digital capture throughout the facility
      because of its flexibility, productivity and cost-effectiveness. We now use CR
      systems to handle six exam rooms and portable exams conducted by the radiology
      department, as well as imaging studies conducted in two ER exam rooms. Before
      committing to a CR vendor, we conducted an eight-week, side-by-side pilot study
      with two vendors' systems. One CR system was located in the emergency room and
      the other unit was located in the main radiology department. Our staff received
      education and training from both vendors. I led an evaluation team that included
      representatives from the radiology group, the information services (IS)
      department, biomedical engineering, staff physicians, ER physicians,
      pulmonologists and orthopedic specialists. Our team met to design the trial and
      develop a list of factors that technologists would use to evaluate the two
      systems. The team met after installation and again after the trial was complete
      to provide verbal input on each vendor for each category and to review feedback
      from the technologists' survey. Categories included image quality, interactions
      with each vendor's sales and service staff, workflow, time studies, durability of
      cassettes and plates, entry of John Doe patients for ER, and other factors. After
      the trial, we chose a system by unanimous vote. We learned a lot about CR
      technology throughout this process. Overall we are extremely satisfied with the
      platform we selected and with this method of evaluating the two systems prior to
      making this important decision.

PMID- 12800562
TI  - Web-based X-ray quality control documentation.
AB  - The department of radiology at the Medical College of Georgia Hospital and
      Clinics has developed an equipment quality control web site. Our goal is to
      provide immediate access to virtually all medical physics survey data. The web
      site is designed to assist equipment engineers, department management and
      technologists. By improving communications and access to equipment documentation,
      we believe productivity is enhanced. The creation of the quality control web site
      was accomplished in three distinct steps. First, survey data had to be placed in
      a computer format. The second step was to convert these various computer files to
      a format supported by commercial web browsers. Third, a comprehensive home page
      had to be designed to provide convenient access to the multitude of surveys done
      in the various x-ray rooms. Because we had spent years previously fine-tuning the
      computerization of the medical physics quality control program, most survey
      documentation was already in spreadsheet or database format. A major technical
      decision was the method of conversion of survey spreadsheet and database files
      into documentation appropriate for the web. After an unsatisfactory experience
      with a HyperText Markup Language (HTML) converter (packaged with spreadsheet and
      database software), we tried creating Portable Document Format (PDF) files using
      Adobe Acrobat software. This process preserves the original formatting of the
      document and takes no longer than conventional printing; therefore, it has been
      very successful. Although the PDF file generated by Adobe Acrobat is a
      proprietary format, it can be displayed through a conventional web browser using
      the freely distributed Adobe Acrobat Reader program that is available for
      virtually all platforms. Once a user installs the software, it is automatically
      invoked by the web browser whenever the user follows a link to a file with a PDF
      extension. Although no confidential patient information is available on the web
      site, our legal department recommended that we secure the site in order to keep
      out those wishing to make mischief. Our interim solution has not been to password
      protect the page, which we feared would hinder access for occasional legitimate
      users, but also not to provide links to it from other hospital and department
      pages. Utility and productivity were improved and time and money were saved by
      making radiological equipment quality control documentation instantly available
      on-line.

PMID- 12800563
TI  - Success with Web-based image access.
AB  - The University of Mississippi Medical Center in Jackson, Miss., is the only
      medical school in the state. We performed 235,000 procedures in the 2001-02
      fiscal year. All imaging services within the radiology department are networked
      to a PACS and are filmless. The elimination of film required that we decentralize
      our traditional file room to allow easy access to our radiology network across
      the campus. In our facility, there are three levels of image access: Diagnostic
      Quality, Review Quality and Web Access. Diagnostic Quality requires top-of-the
      line workstations and monitors and is the most expensive. Review Quality
      workstations represent some savings over Diagnostic and are used in the ICU,
      orthopedics and surgery. Web Access appears to satisfy most areas outside the
      main diagnostic department. The account set-up procedure is simple because it
      uses our intranet email system. Images are easily pasted into presentation
      applications for articles and conferences. However, the main advantage of Web
      Access is the low cost. The downside of Web Access is that the images are for
      review only and are limited by the quality of the monitor in use. It is also
      somewhat cumbersome to retrieve old or comparison images via this method. The Web
      only holds approximately 45 days of the most recent images, therefore older
      studies may not be available. The deployment of this Web-based service has aided
      in our efforts to reduce the amount of film we print and has also been beneficial
      in improving patient care through faster service.

PMID- 12800564
TI  - Six Sigma: not for the faint of heart.
AB  - Six Sigma is an excellent quality and performance improvement tool. Like any
      tool, the results of using it are highly dependent on whether you use it with
      competence and on the right problem. This article will help you decide if your
      problem is well-suited for a Six Sigma approach and will suggest the optimum
      approach for planning and implementing Six Sigma methodology. Performance
      improvement methods can be grouped into two broad categories, based on the
      problem to be addressed. When the problem is relatively minor and localized,
      "evolutionary" methods may be suitable (e.g., quality circles, problem-solving
      staff meetings, continuous quality improvement [CQI], total quality management
      [TQM]). These tools work best when modest incremental improvements are sought,
      when major process redesign is not thought to be necessary, and when the
      avoidance of workplace disruption is desired. Reengineering and Six Sigma are the
      best-known examples of the "revolutionary" performance improvement methods. These
      methods should be used when major (drastic, do or die, etc.) improvements are
      needed. Problems that cross departmental boundaries need these methods. When a
      process is so dysfunctional that you feel like you need to tear up the standard
      operating procedure (SOP) and start all over again, you need a revolutionary
      method. A Six Sigma project requires a major expenditure of money and employee
      time, and a willingness to make some hard decisions about jobs, employee
      retention and relationships among stakeholders. An institution's culture should
      be considered as part of the decision about using Six Sigma. If the institution
      has a history of making data-driven decisions, or at least has displayed openness
      to operating in that manner, Six Sigma has a good chance of success. A radiology
      driven Six Sigma project should not be undertaken until a comprehensive written
      description of the scope of the project is approved by the radiology department
      leadership team and by the appropriate higher-level institutional leaders. This
      document should address the specific outcomes desired, the resources available, a
      rough tentative timeline, and any political constraints imposed on the project
      (e.g., inviolate HR policies, compatibility with enterprise strategic goals). The
      document should be comprehensive enough and explicit enough to be useful as a
      major component of the bid package for hiring a consultant or for writing the job
      description for the hiring of an in-house expert. A full-time project manager
      should be designated if an in-house expert is not hired. This person should be a
      senior leader in the department, but not the department director. Leading a Six
      Sigma project is a full-time job in itself and cannot be performed as an
      additional duty. Although it may be tempting to appoint a senior staff
      technologist or nurse, keep in mind that the project manager must have sufficient
      authority to expect cooperation from departmental supervisors without resorting
      to frequent appeals to the department director. Contact the institution's CIO and
      ask that a knowledgeable person on the IT staff be appointed to serve as the IT
      liaison for the project. This person should have in-depth familiarity with the
      HIS and the ways that it interfaces with the RIS (if the RIS is not a module
      within the HIS). Most importantly, this liaison must understand the exact data
      definitions and the origins of the data that are passed between the HIS and the
      RIS. The steering committee should consist of at least one physician and one
      department-level administrator from outside of the radiology department. From
      within the radiology department, there should be at least one radiologist and one
      senior modality manager (whose modality is not the primary focus), the project
      manager, and the manager of a radiology component that is a focus of the project
      (e.g., the film library manager). The consultant should be an ex officio member
      without vote. The steering committee should be small enough to be manageable, yet
      large enough to provide insight from both the radiology department and the rest
      of the institution. Because of the size of the steering committee and the
      difficulty of bringing so many people together for meetings, the day-to-day
      governance of the project will be provided by an informal "operations committee."
      When we consider "change" in the context of a Six Sigma project, we talk about a
      wide variety of topics, but they can be summarized usefully as dealing with
      processes, policies, physical plant and equipment, personnel, and politics (or
      culture). The first three of these lend themselves to quantitative analysis, or
      at least rigorously qualitative analysis. The final two, however, are subjective,
      ill-defined or not readily acknowledged, and fraught with potentially major
      challenges when it becomes necessary to implement changes in the first three. The
      Six Sigma process, as taught by GE, consists of five phases summarized by the
      acronym DMAIC: Define, Measure, Analyze, Improve and Control. This article deals
      mostly with the time period from first consideration of a possible Six Sigma
      project through the early part of the Define phase. It also discusses pitfalls
      that must be considered anytime throughout a project, from first thoughts of
      conducting a project until recommended changes become ingrained in the
      department's operations. Six Sigma compares baseline or historical data to data
      obtained after implementation of Six Sigma-driven changes in order to determine
      if desired changes in performance have been achieved. When historical data are
      not available, the Six Sigma team must collect baseline data as one of their
      earliest tasks. A Six Sigma project can easily last 18 to 24 months or longer. We
      must be sure that the data we collect during Month 18 are collected identically
      to the data we collected at baseline. A major performance improvement project is
      likely to require 12 to 24 months or longer. Upper management initially may be
      reluctant to appoint the "cream of the crop" to the project teams. Success is
      predicated on having the most knowledgeable personnel involved in the project.
      Without them, the chances of success are reduced. A Six Sigma project's length
      always exceeds the attention span of the vast majority of its participants. The
      department director and project manager must anticipate this and devote special
      efforts to maintaining motivation and momentum after the initial flurry of
      activity. The complexity of a Six Sigma project will be greatly increased, and
      all of the pitfalls discussed here will be exacerbated, if your facility has
      multiple sites. At the simplest, the multiple sites will introduce complications
      in getting personnel to come to project meetings. The complications will escalate
      if the sites are under different management, such as a confederated health
      system. The project manager and the consultant will expend additional time and
      effort dealing with these issues, which likely will lengthen the project
      unavoidably. The project manager must spend time with the department's external
      customers who have significant stakes in the project. At a minimum, this should
      include relatively formal meetings with other department directors or subordinate
      managers and key physician and nurse leaders, and attendance at their managerial
      or staff meetings (you may need to ask to be invited). Although paper or e-mail
      surveys can be helpful, only sustained personal contact with a stakeholder will
      truly allow you to understand how they interact with radiology and what their
      concerns are. As with daily operational management, a performance improvement
      project requires attention to policies, procedures, processes, physical plant and
      infrastructure, personnel, and perhaps most importantly, to politics.

PMID- 12800565
TI  - Imaging center PACS.

PMID- 12800566
TI  - Best of both worlds.

PMID- 12800567
TI  - Research and scholarship among R.T. educators.
AB  - Full-time registered radiologic technologist educators were surveyed to determine
      their professional profile and research/scholarship productivity. Overall,
      research and scholarship productivity was low. More than 85% of respondents had
      not authored an article in a peer or nonpeer-reviewed journal, although more than
      half of the sample reported other scholarly activities, such as reviewing books,
      developing continuing education material and presenting at professional meetings.
      As a group, full-time educators employed in 4-year institutions and holding a
      higher academic degree were more productive in research and scholarship.

PMID- 12800568
TI  - Mammography coding and reimbursement.
AB  - This article describes mammography coding and reimbursement, coding
      responsibilities for personnel and the importance of coding accuracy. After
      completing this article, the reader will: Recognize basic terms associated with
      mammography coding and reimbursement. Explain reimbursement differences between
      screening and diagnostic mammography. Understand the responsibilities of
      mammography facility personnel in accurate coding. Recognize the impact of
      coding, reimbursement and regulation on the economics of mammography practice.
      Explain basic coding concepts for screening, diagnostic and follow-up
      mammographic studies. Describe some new breast imaging technologies reimbursed by
      Medicare.

PMID- 12800569
TI  - Productivity and quality patient care.
AB  - Because of the need to control rising U.S. health care costs, managers today not
      only must focus on their staff and patients, but also on the business aspects of
      radiology, such as increasing productivity. Balancing productivity with quality
      patient care is not an easy task--it requires changes by the entire radiology
      team, including managers, technologists and radiologists. After completing this
      article, the reader should be able to: Discuss why health care costs continue to
      rise. Define productivity, how it can be measured and why it must be measured in
      today's health care settings. Recognize how patient satisfaction contributes to a
      health care organization's bottom line. Understand the health care team's role in
      simultaneously increasing productivity and patient satisfaction.

PMID- 12800570
TI  - Dangers of high-dose fluoroscopy.

PMID- 12800571
TI  - Transfer of training through CE.

PMID- 12800572
TI  - Hidden Agenda.

PMID- 12800573
TI  - CE--in the eye of the beholder.

PMID- 12800574
TI  - A little poison can be good for you.

PMID- 12800575
TI  - How Genentech got it.

PMID- 12800576
TI  - How the street sees biotech.

PMID- 12800578
TI  - Democratic prescriptions. Presidential hopefulls offer health insurance
      solutions, while a new report questions how many Americans really are uninsured.
AB  - Democrats see a weakness in President Bush's healthcare policies, and
      presidential hopefulls are coming forward with solutions to the uninsured crisis.
      Sen. John Kerry of Massachusetts, left, wants to contain costs while also
      increasing coverage, at a cost of $80 billion per year. Former Vermont Gov.
      Howard Dean and Rep. Dennis Kucinich also outlined their plans last week.

PMID- 12800577
TI  - Taking on Viagra.

PMID- 12800579
TI  - Proposal for new ER standard puts providers on the defensive. JCAHO's public
      comment period opens as evidence shows that treatment delays lead to patient
      deaths.

PMID- 12800580
TI  - A conflict of interest. Providers use GAO report to push for stricter
      legislation.

PMID- 12800581
TI  - Extension tension. Is the industry ready for electronic standards?

PMID- 12800582
TI  - Smallpox vaccine program lagging.

PMID- 12800583
TI  - Doing the drill. Hospital staffs get inventive during bioterror drills.

PMID- 12800584
TI  - Transfer trauma. Hospitals oppose CMS plan to include more DRGs in controversial
      policy.

PMID- 12800585
TI  - Weighing in on assisted living. Report to Senate panel seeks quality improvements
      in growing industry.

PMID- 12800586
TI  - Legal payback? Ruling could force hospitals to give back lien funds.

PMID- 12800587
TI  - Docs say: no sale. Ala. docs angered by possibility Baptist Health System will be
      sold to for-profit.

PMID- 12800588
TI  - The way forward. Legislation, investment needed to achieve uniformity of
      healthcare data.

PMID- 12800589
TI  - An army of patients. The VA struggles with a growing population of veterans using
      its healthcare system as it works to boost quality and capacity.

PMID- 12800590
TI  - Marching orders. Tricare restructuring, rebidding designed to cut costs, improve
      quality.

PMID- 12800591
TI  - Beyond the rebound. HFMA's annual conference will use 'personal' tone to address
      issues facing execs.

PMID- 12800592
TI  - By the numbers. Top healthcare equity underwriters.

PMID- 12800593
TI  - A new baby debate.

PMID- 12800594
TI  - Chipping away at Roe.

PMID- 12800595
TI  - Preemies grow up.

PMID- 12800596
TI  - Holes in the safety net. A startling number of sex offenders are off the grid.

PMID- 12800597
TI  - Our bodies, our fears.

PMID- 12800598
TI  - Coping with anxiety.

PMID- 12800599
TI  - We need more than duct tape.

PMID- 12800600
TI  - Irinotecan: promising activity in the treatment of malignant glioma.
AB  - Patients with malignant glioma continue to have a dismal outcome. Those with
      glioblastoma multiforme, the most common type of malignant glioma, have a median
      survival of 40 to 60 weeks following diagnosis and only 16 to 24 weeks after
      recurrence. While standard therapy is surgery and external-beam radiotherapy,
      data indicate that chemotherapy improves the clinical outcome of some patients.
      Irinotecan (CPT-11, Camptosar) possesses significant activity against malignant
      glioma, and potentiation of this activity with combination partners, including
      the alkylator 1,2-bis(2-chloroethyl)-1-nitrosourea (carmustine, BCNU), is being
      evaluated in an ongoing phase II study. Also, the combination of irinotecan plus
      temozolomide (Temodar) has produced synergism in preclinical studies as well as
      encouraging responses in ongoing clinical trials. Other investigative directions
      include studies of irinotecan plus temozolomide and O6-benzylguanine (O6-BG) to
      assess the ability of O6-BG to maximize the therapeutic benefits of irinotecan
      combined with temozolomide.

PMID- 12800601
TI  - Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme.
AB  - Radiation therapy has traditionally been the treatment of choice for locally or
      regionally advanced cancer, but its therapeutic efficacy is often hindered by
      limited tolerance of normal tissues and by tumor radioresistance. To improve
      therapeutic outcome, radiotherapy is frequently combined with chemotherapeutic
      drugs that are themselves cytotoxic and may sensitize cells to radiation. Solid
      evidence exists that administering standard chemotherapeutic agents during the
      course of radiotherapy (concurrent chemoradiotherapy) increases both local tumor
      control and patient survival in a number of cancer sites. These therapeutic
      improvements, however, have been achieved at the expense of considerable normal
      tissue toxicity. To improve chemoradiotherapy further, there have been extensive
      explorations of the potential of newer chemotherapeutic agents, including
      irinotecan (CPT-11, Camptosar) and other topoisomerase inhibitors. Preclinical
      studies have shown that these agents are potent radiosensitizers, providing a
      strong biologic rationale for using these drugs in combination with radiotherapy.
      These studies also generated information critical for designing effective
      treatment schedules in clinical settings. The therapeutic efficacy of
      topoisomerase inhibitor-radiation combinations is currently being tested
      clinically. Recent advances in molecular biology have discovered many cellular
      molecules, including the cyclooxygenase-2 (COX-2) enzyme, that promote tumor cell
      survival and are responsible for tumor resistance to cytotoxic agents, and hence
      may serve as potential targets for augmentation of radio (or chemo) response. COX
      2 is often overexpressed in premalignant lesions and cancer, and is involved in
      carcinogenesis, tumor growth, and metastatic spread. Preclinical studies provided
      solid evidence that inhibition of this enzyme with selective COX-2 inhibitors
      prevents carcinogenesis, slows the growth of established tumors, and enhances
      tumor response to radiation without appreciably affecting normal tissue
      radioresponse. The mechanisms of enhancement of tumor radioresponse involve
      direct actions on tumor cells and indirect actions, primarily on tumor
      vasculature. COX-2 inhibitors also improve tumor response to chemotherapeutic
      agents, including irinotecan. Additional therapeutic benefit was observed for
      celecoxib (Celebrex), a selective COX-2 inhibitor, consisting of a strong
      reduction in irinotecan-induced diarrhea. Thus, selective targeting of COX-2 may
      potentially improve radiotherapy, chemotherapy, or chemoradiotherapy--a
      therapeutic strategy that is currently being tested in clinical trials.

PMID- 12800602
TI  - Rationale for mitomycin and irinotecan use in advanced breast cancer.
AB  - For women who develop hormone-refractory metastatic breast cancer, or who have
      breast cancers that are not estrogen-dependent (hormone receptor-negative),
      treatment with chemotherapy is the best option. Mitomycin (Mutamycin) and
      irinotecan (CPT-11, Camptosar) have marginal activity in breast cancer. However,
      the sequential administration of mitomycin and irinotecan appears to have
      synergism in preclinical studies, as mitomycin upregulates the level of
      topoisomerase I, the target of irinotecan. A phase I clinical trial of
      pharmacologically based sequential administration of mitomycin on day 1 followed
      by irinotecan on days 2 and 8 was performed in previously treated solid tumor
      patients. In five heavily pretreated women with breast cancer, one patient had a
      complete response, one patient had a partial response, and one patient had stable
      disease. Upregulation of topoisomerase I gene expression in peripheral blood
      mononuclear cells was observed in two of the responding patients. A phase II
      trial of mitomycin followed by irinotecan in women with previously treated
      metastatic, inflammatory, or locally advanced breast cancer is currently ongoing.

PMID- 12800603
TI  - Japanese ovarian trials: focus on irinotecan.
AB  - Irinotecan (CPT-11, Camptosar) has achieved a response rate of 23.6% in recurrent
      ovarian cancer. Irinotecan/cisplatin combination chemotherapy has shown a
      response rate of 33% in platinum-resistant ovarian cancer, and 76% when used as
      the initial regimen for ovarian cancer. Regarding dose-limiting toxicity,
      although neutropenia and diarrhea were observed, diarrhea was thought to cause no
      remarkable problems in the combination regimen examined. Based on these results,
      irinotecan is considered to be a useful drug in chemotherapy for ovarian cancer.

PMID- 12800604
TI  - Toxicity associated with carboplatin/paclitaxel/Irinotecan use in advanced
      ovarian cancer: preliminary analysis.
AB  - Despite the high objective response rate of advanced ovarian cancer to
      combination platinum/taxane-based chemotherapy, the majority of patients
      ultimately experience disease progression. Thus, there is a need to find new
      management strategies that can improve upon the results of existing therapies. We
      are currently conducting a phase II trial to explore the toxicity and potential
      efficacy of a three-drug program, which adds irinotecan (CPT-11, Camptosar) at
      100 mg/m2 to carboplatin (Paraplatin) at an area under the concentration-time
      curve of 5 and paclitaxel at 150 mg/m2 over 3 hours. Treatment was initially
      given on an every-3-week schedule, but was subsequently changed to an every-4
      week schedule due to excessive bone marrow toxicity. The study remains in
      progress, with 26 patients currently evaluable for toxicity, which has included
      grade 4 neutropenia (42% incidence), grade 4 thrombocytopenia (12%), and grade 3
      emesis (12%), with one patient each experiencing grade 3 diarrhea, hepatic
      dysfunction, and insomnia. Data regarding response rates are immature. Our
      preliminary analysis reveals that the combination of
      carboplatin/paclitaxel/irinotecan can be administered to women with advanced
      ovarian cancer with significant, but overall acceptable, toxicity. Randomized
      trials will be required to define a possible role for this three-drug combination
      chemotherapy regimen in the standard management of advanced ovarian cancer.

PMID- 12800605
TI  - Phase I. Trial of irinotecan plus carboplatin in two dose schedules.
AB  - A phase I study of carboplatin (Paraplatin) administered in two different dosing
      schedules (single dose every 4 weeks and weekly dosing) in combination with
      weekly irinotecan (CPT-11, Camptosar) was conducted in patients with relapsed or
      refractory advanced malignancies. Fifty-three patients with a variety of tumor
      types were randomly enrolled on the two different treatment regimens and have
      received a total of 163 cycles of treatment to date. Twenty-six patients received
      weekly irinotecan in combination with a single fixed dose of every-4-week
      carboplatin (arm 1). Initially, patients received irinotecan on days 1, 8, and
      15, in combination with fixed-dose carboplatin at an area under the concentration
      time curve (AUC) of 5.5 (Calvert formula) on day 1 every 28 days. Due to dose
      limiting toxicities encountered at the first two dose levels, the protocol was
      amended to decrease the fixed dose of carboplatin to an AUC of 4.0 every 4 weeks.
      Dose-limiting toxicity was again encountered, so the day-15 dose of irinotecan
      was eliminated from the dosing regimen. The recommended phase II dose for heavily
      pretreated patients is irinotecan at 60 mg/m2 on days 1 and 8 in combination with
      carboplatin at AUC 4.0 on day 1 with cycles repeated every 28 days. Twenty-seven
      patients were treated with weekly irinotecan in combination with fixed-dose
      weekly carboplatin (arm 2). The initial dosing regimen consisted of irinotecan in
      combination with fixed-dose carboplatin at an AUC of 1.8 on days 1, 8, and 15,
      with treatment cycles repeated every 28 days. Due to the development of dose
      limiting toxicities at the first two dose levels, the dosing regimen was
      subsequently amended to weekly irinotecan in combination with fixed-dose
      carboplatin at AUC 2.0 on days 1 and 8 only, and the dosing interval was
      shortened to every 21 days. With this amended regimen, the recommended phase II
      doses are irinotecan at 90 mg/m2 in combination with carboplatin at AUC 2.0 on
      days 1 and 8, with treatment cycles repeated every 21 days.

PMID- 12800606
TI  - Phase I. Trial of irinotecan and temozolomide in patients with solid tumors.
AB  - This phase I study was conducted to determine the dose-limiting toxicity, maximum
      tolerated doses, and recommended phase II doses of the combination of irinotecan
      (CPT-11, Camptosar) and temozolomide (Temodar). Patients have received irinotecan
      and temozolomide on one of three different dosing schedules: (1) oral
      temozolomide on days 1-14 plus a single i.v. dose of irinotecan on day 8 every 28
      days (arm 1); (2) weekly i.v. irinotecan on days 1, 8, 15, and 22 plus oral
      temozolomide on days 1-7 and 15-21 every 42 days (arm 2); and (3) every-other
      week i.v. irinotecan on days 1 and 15 plus oral temozolomide on days 1-7 and 15
      21 every 28 days (arm 3). A total of 49 patients have received 112+ cycles of
      therapy on all three dosing schedules to date. Dose-limiting toxicity consisting
      of diarrhea, neutropenia, and thrombocytopenia was encountered at a temozolomide
      dose of 125 mg/m2/d and an irinotecan dose of 250 mg/m2 on treatment arm 1. As a
      result, the protocol has been amended to explore lower doses of temozolomide in
      combination with higher doses of irinotecan, and patient accrual is currently
      continuing. Dose-limiting grade 3 diarrhea, nausea, and vomiting were reported in
      7/12 patients enrolled on the two dose levels explored on treatment arm 2, so
      this dosing regimen was considered intolerable. Patient accrual currently
      continues at dose level 1 of treatment arm 3, so it is too early to determine
      dose-limiting toxicities and recommended phase II doses for this treatment
      schedule. Two partial responses have been reported to date in patients with
      glioblastoma and head and neck cancer, respectively. One evaluable response has
      also been observed in a patient with metastatic colorectal cancer. Irinotecan
      weekly x 4 plus temozolomide on days 1-7 and 15-21 is intolerable due to the
      development of dose-limiting gastrointestinal toxicities. The recommended phase
      II doses of irinotecan and temozolomide on treatment arms 1 and 3 remain to be
      determined as patient accrual is currently ongoing.

PMID- 12800607
TI  - Combined inhibition of topoisomerases: a phase I. Study of irinotecan and
      epirubicin.
AB  - Preclinical data suggest that the combination of inhibitors of topoisomerases I
      and II may be synergistic when administered together. The optimal sequence of
      such combinations is uncertain, but initial administration of a topoisomerase I
      inhibitor upregulates topoisomerase II. Several combinations of these inhibitors
      have been evaluated, but have not clearly demonstrated synergy. Thus, we have
      started a phase I study of the combination of irinotecan (CPT-11, Camptosar) and
      epirubicin (Ellence). Typical eligibility criteria for phase I studies were
      employed. Patients with a history of congestive heart failure, > 240 mg/m2 of
      prior doxorubicin, or > 10% weight loss in the prior 4 weeks were excluded.
      Irinotecan and epirubicin were administered on days 1 and 8, every 28 days.
      Initially, patients were treated with irinotecan at 100 mg/m2 and epirubicin at
      40 mg/m2 (dose level 1). After substantial toxicity at this level, the doses to
      be evaluated were changed to irinotecan: 50-->75-->100 mg/m2, and epirubicin: 20-
      >25-->30 mg/m2. Dose-limiting toxicities were noted in 2/4 patients (2
      neutropenic fever, 1 thrombocytopenia) on dose level 1; 0/3 on dose level 1A; 1/8
      (neutropenia) on dose level 2A; and 1/3 (neutropenia) on dose level 3A. This is
      the first combination of irinotecan and epirubicin to be evaluated in humans. The
      toxicity, primarily myelosuppression, noted to date has exceeded the expected
      toxicity for the doses of the irinotecan and epirubicin alone, suggesting the
      possibility of a synergistic interaction of the agents on this schedule, at least
      in the bone marrow. Other toxicities were acceptable and non-dose-limiting.
      Accrual of patients continues, at level 3A (irinotecan at 75 mg/m2, epirubicin at
      25 mg/m2).

PMID- 12800609
TI  - Boost contract performance by managing retro adds, deletes.

PMID- 12800608
TI  - Irinotecan treatment in cancer patients with UGT1A1 polymorphisms.
AB  - At the present time, pharmacogenetic investigation of irinotecan (CPT-11,
      Camptosar) therapy is mainly focused on the clinical relevance of genetic
      variation in the UDP-glucuronosyltransferase (UGT1A1) gene. The glucuronidation
      of the potent topoisomerase I inhibitor SN-38 is a major inactivation pathway of
      irinotecan metabolism. UGT1A1 genotypes associated with Gilbert's syndrome (a
      mild intermittent hyperbilirubinemia) are characterized by reduced
      glucuronidation of SN-38. Such UGT1A1 genetic variants have different
      distribution across individuals of different ethnicity. The (TA)n TAA
      polymorphism in the promoter is more frequent in Caucasians as compared to
      Asians, in whom missense polymorphisms in the exons are more common. Two recent
      pharmacogenetic trials (one performed in the United States and the other in
      Japan) investigated the clinical significance of UGT1A1 gene mutations for both
      the pharmacokinetics of irinotecan metabolites and the toxicity profile. The
      results of these association studies showed that preliminary genotyping of the
      (TA)n polymorphism might predict the occurrence of toxicity in genetically
      predisposed patients.

PMID- 12800610
TI  - Cap check helps reconcile payments with eligibility lists to improve cash flow.
AB  - Some capitated provider groups are becoming more adept at using software
      solutions to effectively manage retroactive deletions, additions and changes in
      membership enrollment. While a variety of software programs are available,
      several sources recommend using Cap Check to help match up eligibility lists with
      capitation payment.

PMID- 12800611
TI  - Capitated groups need to 'get back to basics'.

PMID- 12800612
TI  - Capitation building momentum in latest MGMA group practice data.

PMID- 12800613
TI  - Local anesthetics: special considerations in endodontics.
AB  - Local anesthetics are essential for successful endodontic treatment, and their
      pharmacologic characteristics have special implications for the treatment of
      painful, chronically-inflamed or necrotic teeth. Their dosages must be limited to
      prevent toxicity, which may be enhanced by the coadministration of sedative
      agents or drugs which affect hepatic drug metabolism. Endodontic patients with
      established central and peripheral sensitization represent special challenges for
      pain control, since morphogenetic changes resulting from neurogenic inflammation
      can render pain fibers more resistant to local anesthesia. The use of
      vasconstrictors with conventional and alternative injection techniques, e.g.,
      intraosseous injections, are necessary to prolong the duration of action of local
      anesthesia but can place patients with cardiovascular disease at some risk. An
      appreciation of all of these aspects of local anesthesia in endodontics will
      better prepare the operator for predictably safe and effective patient care.

PMID- 12800614
TI  - Pulpalgia, the pimpernel of pain.

PMID- 12800615
TI  - Strategies for managing the endodontic pain patient.

PMID- 12800616
TI  - Use of nickel titanium instruments for cleaning and shaping root canal systems.

PMID- 12800617
TI  - The management of traumatic dental injuries.
AB  - Traumatic injuries require a vast and complex treatment methodology. This
      manuscript although in a "cookbook" format will still require from the
      practitioner sound clinical judgment prior to treating a traumatized tooth.

PMID- 12800618
TI  - Diagnosis and treatment planning: cracked tooth.

PMID- 12800621
TI  - Don't forget about the office staff.

PMID- 12800622
TI  - Healing environments.

PMID- 12800623
TI  - A break from tradition. Patients are embracing alternative treatments. Now it's
      time for hospitals to do the same.

PMID- 12800624
TI  - Success is in the details. Twenty real-world tips for managing your brand online.

PMID- 12800625
TI  - Bridging the gap. Relationship marketing breathes new life into neglected
      populations.

PMID- 12800626
TI  - Stop measuring patient satisfaction. To build loyalty, hospitals need to exceed
      customers' expectations.

PMID- 12800627
TI  - Treating patients like customers. Despite recent gains, healthcare still has a
      lot to learn about measuring satisfaction. Interview by Richard K. Thomas.

PMID- 12800628
TI  - Make life a little easier. Online prescriptions reap rewards for doctors and
      patients.

PMID- 12800629
TI  - Lessons in de-branding. To revitalize a well-known brand, sometimes you have to
      take it apart.

PMID- 12800630
TI  - We are the voice of the customer. Marketers must push to meet consumer needs.

PMID- 12800631
TI  - Referral channel management: fueling the economic engine.

PMID- 12800632
TI  - PinnacleHealth Heart and Vascular Institute: how one hospital successfully
      survived a merger of two major cardiovascular programs.

PMID- 12800633
TI  - Annualized Medicare cardiovascular impact of October 1, 2001 DRG changes and
      potential impact of related APC changes effective April 1, 2002: one tertiary
      center's experience.

PMID- 12800634
TI  - Request for proposal (RFP) essentials.

PMID- 12800635
TI  - Looking safety straight in the eye.

PMID- 12800636
TI  - Working around the clock.

PMID- 12800637
TI  - The use of endoscopic retrograde cholangio pancreatography.
AB  - Endoscopic retrograde cholangio pancreatography (ERCP) combines endoscopic and
      radiographic techniques and is carried out to allow detailed examination of the
      bile ducts, pancreatic duct and gallbladder. It can serve as a diagnostic or
      therapeutic tool. This article provides an update on the procedure as well as
      indications and contraindications. The nurse's role in caring for patients
      undergoing ERCP--which includes preparing them for the procedure, observing them
      post-ERCP and providing health education for discharge and beyond--is also
      covered.

PMID- 12800638
TI  - What you need to know about... psoriasis.

PMID- 12800639
TI  - Colonoscopy.

PMID- 12800640
TI  - Epilepsy: its presentation and nursing management.
AB  - Nearly 25,000 people in the UK develop epilepsy each year, making it one of the
      most common serious neurological conditions. The form a seizure takes depends on
      where it starts in the brain and how far it spreads. Nurses need to recognise the
      different types of epileptic seizure and the appropriate nursing management of
      each. National guidance on how epilepsy services can be improved will be
      published by the government and will include a national service framework for
      long-term conditions, including epilepsy.

PMID- 12800641
TI  - Dissociation in adults with a diagnosis of substance abuse.
AB  - Dissociation is a defence mechanism whereby individuals under stress separate
      affect and/or behaviour from the normal flow of consciousness. It is common in
      people who have experienced trauma. A Dissociative Experience Scale was used to
      study 51 subjects who were members of inpatient or outpatient substance abuse
      programmes. Thirty per cent of the group scored 15 or higher, suggesting that
      dissociative events are common in this population. Nurses need to understand the
      phenomenon of dissociation and the relationship between trauma, dissociation and
      substance abuse. This will enhance their assessment of patients and increase
      their knowledge base regarding appropriate treatment.

PMID- 12800643
TI  - The new gatekeepers.

PMID- 12800642
TI  - Reminding patients that there's still hope.

PMID- 12800644
TI  - A rapid access and early discharge service for people with COPD.
AB  - The British Thoracic Society (1997) defines chronic obstructive pulmonary disease
      (COPD) as a chronic, slowly progressive disorder that causes significant
      mortality and morbidity. In most cases it is caused by smoking tobacco.

PMID- 12800645
TI  - Supportive and palliative care for patients with COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is the most common respiratory
      disorder in the UK (Shee, 2001). In 1999, the number of people who died of COPD
      was equal to the number who died of lung cancer (Hill and Muers, 2000). Patients'
      knowledge of the high level of morbidity of this disease has a large impact on
      their social, psychological and economic status (Addington-Hall et al, 1998).
      Patients with COPD, unlike those with lung cancer, may go from crisis to crisis,
      requiring many hospital admissions, and are more likely to die in hospital after
      an acute admission (Edmonds et al, 2001).

PMID- 12800646
TI  - Developing effective services for people with COPD.
AB  - In terms of health care resources, chronic obstructive pulmonary disease (COPD)
      has long been the poor relation of other respiratory conditions such as asthma
      and lung cancer. However, over the last 10 years health professionals have
      recognised the importance of COPD and its cost to society and have been motivated
      to provide an improved service for patients. The first guidelines for the
      management of COPD were published by the British Thoracic Society in 1997. The
      Global Initiative for Chronic Obstructive Lung Disease followed this document
      with its Global Strategy for the Diagnosis, Management and Prevention of Chronic
      Obstructive Pulmonary Disease (2001).

PMID- 12800647
TI  - Noninvasive ventilation and COPD.
AB  - The British Thoracic Society (BTS) guidelines for noninvasive ventilation (NIV)
      provide overwhelming evidence that NIV is effective in supporting patients with
      acute hypercapnic respiratory failure (AHRF) (BTS, 2002). AHRF, which causes a
      rise in carbon dioxide levels and a fall in pH, is common in patients presenting
      with acute exacerbations of chronic obstructive pulmonary disease (COPD). NIV is
      also beneficial to patients with chest wall deformity and neuromuscular diseases.

PMID- 12800648
TI  - Quality support for schoolchildren.

PMID- 12800649
TI  - [Autotrophic biofilters for oxidation of nitric oxide].
AB  - Carbon foam, a kind of new engineering material as packing material was adopted
      in three fi 50.8 mm biofilters with different pore dimension and a domesticated
      autotrophic nitrite nitrobacteria to investigate the purification of nitrie
      oxide(NO) in air stream. The biofilm was developed on the surface of carbon foams
      using nitrite as its only nitric source. The moisture in the filter was
      maintained by ultrasonic aerosol equipment, which can also minimize the thickness
      of the liquid film. The liquid phase nitrification test was conducted to
      determine the variability and the potential of performance among the three carbon
      foam-based biofilters. The investigation showed that during the NO influent
      concentration of 200 to 800 g/(L.min), the 24PPC (Pores Per Centimeter) carbon
      foam-based biofilters had the greatest potential, achieving removal efficiencies
      of 94% to 98%. The 8PPC and 18PPC carbon foam-based biofilters achieved removals
      efficiencies of 15% to 21% and of 30% to 40%, respectively. Further research
      showed the potential for this system to remove NO from an air stream on the base
      of a steady removal efficiency of 41% to 52% was attained for the 24PPC carbon
      foam-based biofilter at specified NO influent concentrations of 66.97 to 267.86
      mg/m3 and an empty-bed residence time of 3.5 minutes.

PMID- 12800650
TI  - [Screenings of 23 plant species in Beijing for volatile organic compound
      emissions].
AB  - The VOCs emissions from plants are mainly isoprene and monoterpenes, which
      account for 2/3 of the total emissions from biosphere. 23 kinds of typical plants
      in Beijing area were screened to estimate the emission rates of isoprene and
      monoterpenes by adopting a bag-enclosure sampling method followed by a GC-FID
      analysis. It was found that such deciduous trees as Sophora japnica and Salix
      babyloniaca etc. were mainly emitting isoprene and coniferous trees as Pinus
      tabulaetormis mainly released monoterpenes. The study also showed that the
      emission of isoprene were affected by both temperature and Photosynthetic Active
      Radiation (PAR), while monoterpene emissions were mainly temperature-dependent.

PMID- 12800651
TI  - [Toxic effects of hexavalent chromium on the growth of blue-green microalgae].
AB  - A standard method of algal bioassay for determining the toxicity of toxic
      chemicals was applied to the interaction between Cr(VI) and six blue-green
      microalgae. The 96h-EC50 of hexavalent chromium on the growth of Chlorella
      pyrenoidosa, Synechococcus, Spirulina maxima, Spirulina platensis, Selenastrum
      capriornutum and Scenedesmus quadricauda were 4.96, 6.50, 11.16, 11.74, 12.43 and
      20.89 mg/L, respectively. The tolerance of the six blue-green microalgae to
      Cr(VI) was in the order of Scenedesmus quadricauda > Selenastrum capriornutum >
      Spirulina platensis > Spirulina maxima > Synechococcus > Chlorella pyrenoidosa.
      The sensitivity of these species to Cr(VI) might relate to the cell size, the
      structure of cell wall, as well as the redox reaction caused by the exudate or
      enzyme. X-ray absorption near edge structure(XANES) was used to study the
      accumulation and transformation of Cr(VI) in Chlorella pyrenoidosa.

PMID- 12800652
TI  - [Determination and QSPR study on the electrochemical reduction characteristics of
      chlorinated aromatic compounds].
AB  - The relationship between the reduction characteristics and molecular structure of
      87 chlorinated aromatics including naphthalenes, biphenyls, benzenes and phenols
      was studied by using quantitative structure-property relationship technique. The
      result indicated that there was significant correlation between reduction
      potential and the energy of the lowest unoccupied molecular orbital and the
      number of chlorine atoms in molecule. The study threw more light on the nature of
      reduction process, and provided valuable basic data for designing and optimizing
      treatment process.

PMID- 12800653
TI  - [Endurance and mechanisms of soil urease and dehydrogenase exposed to reactive X
      3B red dye contamination].
AB  - Endurance and mechanisms of urease and dehydrogenase in three Chinese typical
      soils (burozom, cinnamon soil and red soil) exposed to the contamination of
      reactive X-3B red dye were experimentally studied using the microcosmic method.
      The results indicated that the activities of urease and dehydrogenase were both
      promoted in the three soils by reactive X-3B red dye in low dose, 500 and 1000
      mg/L although the stimulating intensity was different from each other. For one
      thing, the activity of urease in burozom was promoted mostly followed by that in
      red soil and that in cinamon was promoted most weakly. For the other, reactive X
      3B red dye in the same concentration could increase the activity of dehydrogenase
      in cinnamon soil most greatly and in burozom most weakly. However, the
      stimulating intensity of urease and dehydrogenase activities in the three soils
      was more and more fainter with the extension of days. Furthermore, reactive X-3B
      red dye in high concentration (3000, 5000 and 10,000 mg/L) could not inhibit the
      activities of urease and dehydrogenase in tested soils. On the contrary, all of
      them remained the level of the activities in unpolluted soils and no toxicity of
      reactive X-3B red dye could reveal with time. Therefore, both enzymes in three
      types of soils had the tolerance to reactive X-3B red dye. Based on the
      experimental data, relevant endurant mechanisms were also analyzed and discussed.

PMID- 12800654
TI  - [The influence of simulated acid rain on acidity and K+ leaching regulation of
      different soil layers].
AB  - The influence of simulated acid rain on acidity and K+ release of different soil
      layers of red soil from Jiangxi was investigated in the lab when surface soil was
      mixed with KCl. The results indicated that pH of leaching solution first
      decreased, then increased in the different soil layers, but pH at the beginning
      moment of leaching existed prominent differences and pH of leachate of pH 2.5
      acid rain in A and AB layers again decreased during subsequent stage. There was a
      peak value of EC of leachate appearing at the beginning stage, it showed that
      nutrient ions in soil rapidly moved downwards into lower depth of profile. K+
      concentration of effluent solution was related to acidity of acid rain and the
      pH2.5 value of acid rain accelerated K+ transportation downwards along profile.
      K+ release of A soil layer was divided into two moments which one was the rapid
      rate of K+ release process at the moment of beginning and then into the middle
      rate of release process. As to pH 4.5 value of acid rain, it also existed rapid
      and slow rate processes.

PMID- 12800655
TI  - [Characteristics of phosphorous losses in surface runoff and sediment under
      different land use in west Tiaoxi catchment].
AB  - Five typical land covers in West Tiaoxi catchment were studied on phosphorous
      loss in artificial rainstorm runoff. Triple duplication experiments were carried
      out under the artificial rain condition with intensity of 2 mm.min-1 lasting 32
      minutes in 3 m2 plot. Transportation and flux of various species of phosphorous
      in runoff and sediments were investigated. The results showed that phosphorous
      losses amount and rate were different among five types of land covers. The loss
      of total phosphorous in runoff of mulberry garden was the largest, which was five
      times higher than that of paddy and pinery field. The majority of total
      phosphorous in runoff was particulate phosphorous. Losses of dissolved
      phosphorous in vegetable plots and mulberry gardens were much higher than bamboo
      plot and paddy field. Loss of dissolved inorganic phosphorous in runoff was the
      main part of dissolved phosphorus, which pinery was much higher than others.
      Total amounts of phosphorous loss from top 10 cm layer of 5 kinds of soils were
      estimated as high as 2.57-4.89 g.m-2, of which phosphorous loss through sediment
      of runoff accounted for more than 97%. The rate of total phosphorous losses were
      ranged in 0.45-4.11 mg.(m2.min)-1 in runoff, which was much lower than that of
      72.82-135.96 mg.(m2.min)-1 in sediment of runoff.

PMID- 12800656
TI  - [Characteristics of nitrogen distribution in peat deposit of freshwater marsh
      wetland].
AB  - Using the methods of sampling in winter and the dividing soil layers in soil
      profiles, the characteristics of TN, NH4(+)-N and NO3(-)-N concentration
      distribution in peat sediments of river bed-flood land and valley depression land
      in Sanjiang Plain where is the most extensive freshwater marsh wetland in China
      were systematically studied. The results showed that NH4(+)-N and NO3(-)-N was
      obviously accumulated in Asc layer, and TN content in Hil layer was the highest
      with the comparing to other layers. TN content in peat sediments was obviously
      increased with the peat particular size decreasing, NH4(+)-N was mainly
      distributed in peat component with 0.149-0.074 mm size, and the most of NO3(-)-N
      was in peat component with 0.03-0.149 mm granule size.

PMID- 12800657
TI  - [Dynamics characteristic of phosphorus loss potential in subsurface runoff from
      rice field].
AB  - A special rice field experiment was conducted to investigate the characteristic
      and mechanism of phosphorus (P) loss potential in subsurface runoff from rice
      field. Teflon Suction Cups (TSC) were inserted into tested plots in 15-20 cm in
      the rice field for water sampling dynamically. The range of molybdate reactive
      phosphorus (MRP) in sub-surface runoff were 0.110-0.273 mg/L, 0.085-0.285 mg/L
      during growth seasons of early rice and later rice, respectively. The magnitude
      of MRP concentrations in subsurface runoff in 15-20 cm from rice field was more
      consistent with trend of soil P accumulation (expressed as Olsen-P) due to P
      application. P concentration and its expected loss loading in the subsurface
      runoff in 15-20 cm in the rice field were not affected by P application combined
      with manure.

PMID- 12800658
TI  - [Effects of land utilization of sewage sludge on grass and soils].
AB  - Effects of land disposal of sewage sludge on grass and soil environment were
      studied. The sewage sludge used was from Northern Shenyang Wastewater Treatment
      Plant. The results showed that contents of nutrient in the soil were increased
      after sewage sludge application, especially for organic matter. Grass biomass
      were increased and the green period were extended with a better growth of the
      lawn. The heavy metal contents in the soil were increased with Cd contents beyond
      2nd grade national environmental quality standard for soils. However, Pb, Cu, Zn
      contents not accumulated heavily. Poa annua had better ability of absorbing and
      accumulating Pb from the sewage sludge. When the application rate of sewage
      sludge capacity was at 25, 30, 60 t.hm-2, Zoysia japonica expressed significant
      absorption and accumulation of Cd, Cu, Zn.

PMID- 12800659
TI  - [Cooperation of mixed culturing bacteria in the hydrogen production by
      fermentation].
AB  - In order to discuss the cooperation of H2-producing fermentation bacteria (HPFB)
      in mixed culture, a batch test fed with glucose and complex organic substance
      (starch, beef, PEP and peptone) respectively, was conducted to investigate the
      effects of mixed culture on H2-producing ability. For the systemic and accurate
      analysis, three kinds of the mixed culture were use to this batch test. It
      included that the mixed culture with five strains of HPFB (B49, H1, LM12, LM11
      and B51), B49 and three stains of non-HPFB (L10, Bacteroide 3-2, Sporobacterl),
      and B49 and hydrogen producing sludge. The results showed that the cooperation of
      mixed culturing bacteria was conditional on the substrates. When fed with
      glucose, which were easily utilized by HPB, the H2-producing ability of HPB was
      restrained because of the competition on the co-substrate between HPB and other
      fermentation bacteria, and it was quite difficult for the cooperation of mixed
      culturing bacteria to be performed. When fed with complex organic substance, the
      H2-producing ability of HPB was enhanced via the cooperation of mixed culturing
      bacteria. Furthermore, a strategy was put forward, that is, different kind of HPB
      cultures could be adopted according to the difference of substrates.

PMID- 12800660
TI  - [Transformation of sulfur forms during coal pyrolysis and partial gasification in
      a fixed bed reactor].
AB  - The development of various process to the pre-desulfurization of coal was drawn
      more attention. In present study, the transformation of sulfur forms of three
      different ranks high sulfur coals during coal pyrolysis and partial gasification
      were investigated in a fixed bed reactor. The sulfur and carbon content analysis
      of original coal and coal char produced were determined by LECO SC-444 and wet
      chemical analysis according to Sugawara's method. The results showed that half of
      inorganic sulfur and partial of organic sulfur were removed during coal
      pyrolysis. And the sulfur removal was much more than carbon during pyrolysis
      process; and the sulfur in the coal char, especially the sulfide sulfur was
      removed completely during partial gasification process for both Datong coal and
      Xishan coal, the degree of sulfide sulfur removal could be increased with
      increasing temperature. At the same time, the results of Yima coal showed that
      the effect of fixed-sulfur by alkaline metals increased when the temperature was
      higher than 700 degrees C, which attribute to the increase of the fixed sulfur
      reaction rate and the decrease of mass-transfer limitation.

PMID- 12800661
TI  - [Numerical simulation of moisture movement in landfill bioreactors under the
      condition of leachate recirculation].
AB  - Landfill bioreactor is a new international development field in the municipal
      solid waste management. It can reduce the difficulty of leachate treatment and
      accelerate the landfill stability process. The general moisture distribution
      rules in landfills were analyzed in this paper and a three dimensional transient
      mathematical model was established to simulate the saturated-unsaturated moisture
      movement under the condition of leachate recirculation to landfills. The model
      was solved by Galerkin finite element method and tested with Theis well formula.
      The functions of different leahcate recirculation designs in landfill bioreactors
      were implemented in the model. Thus, the moisture movement in the landfill could
      be simulated under the condition of leachate recirculation, which provides
      theoretical basis for the effective design and operation of landfill bioreactor.

PMID- 12800662
TI  - [An artificial neural network model for lake color inversion using TM imagery].
AB  - The technology of artificial neural network was used for inversing water quality
      parameters from TM imagery data in the paper in order to study water quality and
      eutrophic status of lake. On the basis of satellite synchronous monitoring
      experiment, a BP neural network model was constructed, in which concentrations of
      SS, CODMn, DO, T-N, T-P and chlo-a were inversed from Landsat TM data and the
      accuracy of which was good, the relative error of which could be controlled below
      25%. Moreover, the reasons of simulating error, ways of improving model and
      applications of the model were also analyzed in detail. The results of this
      research told that based on a small-scale of satellite synchronous experiment,
      the model could be applied successfully in investigation, analysis and estimation
      of lake water quality.

PMID- 12800663
TI  - [Evaluating the fate of gamma-HCH using fugacity model in Tianjin environment].
AB  - This study taking Tianjin as the study area calculated the concentration and
      transfer flux of gamma-HCH in all bulks using Matlab based on the assumption of
      steady state fugacity model. The calculated values agree well with the observed
      values, the concentrations of gamma-HCH in air, water, soil, sediment, fish,
      crop, and vegetable were 1.57 x 10(-11), 7.95 x 10(-7), 1.17 x 10(-4), 4.58 x 10(
      4), 6.03 x 10(-4), 1.60 x 10(-4), 6.42 x 10(-5) mol/m3 respectively. The result
      indicated that the main source of gamma-HCH was agricultural application and
      wastewater from pesticide industries, the biggest bulk sinks were soil and
      sediment (accounting for 99% of total amount in the environment). Among all
      transfer processes deposition and diffusion on the water-sediment and air-soil
      interface were the primary, and mineralization was the key route for gamma-HCH to
      disappear in the environment.

PMID- 12800664
TI  - [Distribution characteristics of metabolites of BHC and derivatives of DDT from
      the agricultural runoff in the western Songnen plain].
AB  - Through analyzing the contents of metabolites of BHC and derivatives of DDT in
      the runoff from paddy and corn land in the Western Songnen Plain, it was found
      that the contents of BHC and DDT were very lower and beta-BHC, which accounted
      for 73.5%-99.5% of the contents of BHC, was the main metabolite of BHC in the
      runoff. Among the derivatives of DDT, only p, p-DDT was detected out. Moreover,
      dissolved form was the dominant species of metabolites and derivatives, but the
      particles size was one of the important factors which affect on the contents of
      BHC and DDT in runoff. The ecological risk of DDT in suspended substance of
      runoff from farmland was lower and BHC had potential risk in the region.

PMID- 12800665
TI  - [Sorption behavior of aldicarb on suspended particulate matter in water].
AB  - Batch adsorption experiments of carbamate pesticide aldicarb on suspended
      particulate matter(SPM) in water were carried out in this paper. The results
      showed that under 25 +/- 1 degrees C, at the aldicarb concentration of 0.2 to 1.5
      mg/L, the adsorption of aldicarb on SPM followed Langmuir isotherm. At the range
      of 2.0 to 15 mg/L, the adsorption followed Freundlich isotherm. And at high
      concentration of 20 to 2000 mg/L the adsorption can be described using both
      Freundlich and Linear isotherms. Factors such as SDBS, TWEEN60, concentration of
      SPM, humic substances, pH, salinity, and microorganism affecting the sorption
      behaviors were also studied.

PMID- 12800666
TI  - [Enhanced sorption of naphthalene into bentonites in water containing
      myristylpyridinium bromide and its mechanism].
AB  - The influence of myristylpyridinium bromide (MPB) on sorption behavior of
      naphthalene into two bentonites in aqueous solution and its mechanism were
      investigated. The apparent sorption coefficients (Kd*) of naphthalene on two
      bentonites with surfactant was dependent on MPB equilibrium concentration (X).
      When X was less than 1/10CMC, the Kd* value increased rapidly with increasing MPB
      primary concentration (X0) that was mainly contributed to increasing the organic
      carbon contents (foc) of bentonites for partitioning naphthalene. The Kd* value
      decreased slowly with increasing X0 when X was intermediate 1/10CMC and 1 CMC,
      because the adding MPB increased foc for sorption naphthalene was less than MPB
      monomer for enhancement solubility of naphthalene. Then The Kd* value decreased
      sharply with increasing X0 when X was larger than 1 CMC, which resulted from that
      the addition of MPB only increased micelle concentration for enhancement
      solubility of naphthalene. The mechanism was explained by apparent partition
      coefficient normalized by foc(i. e. Koc*) for the first time. The relationship of
      1/Koc* and X was linear. The value of Koc, Kmn and Kmc can be calculated from the
      intercept and slope of the linear, which will provide theoretical gist for
      organobentonite applied on organic contaminant remediation.

PMID- 12800667
TI  - [Biodegradable plastic production by activated sludge with different carbon
      sources].
AB  - Polyhydroxyalkanoates(PHAs) are polyesters synthesized by numerous bacteria in
      sludge as intracellular carbon and energy storage compounds under the condition
      of unbalance growth. Another important aspect of PHAs is thermoplastic polyester
      with the remarkable characteristics of biodegradability. In this paper, using
      sodium acetate, sodium propionate and sodium butyrate as the unique carbon
      source, 5.58%, 3.90% and 4.98% PHAs of dry sludge weight were obtained by
      assimilated sludge as PHAs synthesis strains in the anaerobic condition, and
      12.32%, 9.55% and 11.35% PHAs of dry sludge weight were obtained in the anaerobic
      condition. It was shown that there were large quantities strains which could
      accumulate PHAs as granules in the cytoplasm of cells, and the yield of PHAs in
      the anaerobic process were higher than that in the aerobic process. The best
      result was that 12.32% PHAs of dry sludge weight was obtained in the best
      experiment condition, and the yield of the PHAs to substrate was 30.65%. The
      structures of PHAs were analyzed by 1HNMR spectrum, and the relationship of the
      structure of PHAs and the carbon source was explained.

PMID- 12800668
TI  - [Influence of the mixed disinfectant of ClO2 and Cl2 on formation of chloroform].
AB  - The study on influence of mixed solution of ClO2 and Cl2 on formation of
      chloroform from 9 THMs precursors, such as fulvic acid (FA), resorcinol,
      phloroglucinol and cresorcinol etc. under conditions of different ClO2/Cl2 ratio,
      content of precursors, reaction pH, reaction time and reaction temperature etc.
      was studied. Results showed that as the mass percentage of ClO2 in the mixed
      disinfectant was increased, the amount of chloroform formed was reduced; such as
      when mass percentages of ClO2 were 25%, 50% and 75%, CHCl3 formed reduced 55%
      65%, 70%-86% and 80%-93% respectively; until ClO2 was 90%, reduction of CHCl3
      reached 95%-99%. In order to control the formation of chloroform thoroughly, mass
      percentage of ClO2 must be higher than 90%. This provided important scientific
      base for the necessity of using highly pure ClO2 in disinfection and developing
      generator which produced high quality ClO2.

PMID- 12800669
TI  - [Study on electrochemical degradation of acid red B(ARB)].
AB  - The electrochemical degradation of acid red B (ARB) with hydrogen peroxide and
      hypochlorite ion electrogenerated by paired electrooxidation technology was
      investigated. High performance liquid chromatography (HPLC) was used to inspect
      the degradation process of ARB. Through analyzing chromatographic survey and UV
      Vis spectra, as well as the removal of CODCr, TOC and color in the anode and
      cathode cells, the degradation processes of ARB in different cells were
      different. The color removal in the cathode cell was slower than in the anode
      cell, but the CODCr and TOC removal, which were 71.70% and 56.40% respectively,
      was higher than the removal in the anode cell, which were 25.15% and 27.57%. It
      maybe result from the different oxidation capabilities of the electrogenerated
      substances in the anode and cathode cells.

PMID- 12800670
TI  - [Performance of bio-ceramic reactor at low temperature].
AB  - A bio-ceramic reactor for slightly polluted source water from Guanting Reservoir
      in Beijing was conducted at low temperature. It was shown that the removal rate
      of CODMn and NH4(+)-N decreased from 20% to 6%, 90% to 65% respectively when the
      temperature fell from 10 degrees C to 0.5 degree C. The main factor affecting the
      efficiency of bio-ceramic reactor was the microbial activity which decreased more
      than the biomass when the temperature dropped. Microbial activity and biomass in
      the bio-ceramic reactor were in a regular pattern of gradient distribution from
      the lower to the upper along the direction of raw water flow.

PMID- 12800671
TI  - [Experimental study on the treatment of organic wastewater containing
      chlorobenzene by using an EGSB reactor].
AB  - In this paper, the study on the inhibition and recovery of the methanogenic
      activity of the granular sludge which uncontacted and contacted with
      chlorobenzene caused by chlorobenzene, and the study of the treatment of organic
      wastewater containing chlorobenzene by using an EGSB reactor were conducted. The
      results showed that the activity of the granular sludge which had not contacted
      with chlorobenzene would be inhibited by different concentrations chlorobenzene;
      but for the granular sludge which had contacted with chlorobenzene, its activity
      would be inhibited only by higher concentration (100 mg/L) chlorobenzene. Using
      EGSB reactor to treat organic wastewater containing chlorobenzene, when the
      influent chlorobenzene concentration was about 10-50 mg/L, the effluent
      concentration was lower than 7 mg/L before 65 days, but after the 66th day, the
      effluent concentration suddenly reached above 25 mg/L, and after stopping adding
      chlorobenzene, the effluent chlorobenzene concentration was between 3.4-38.32
      mg/L, this showed that the high chlorobenzene removal efficiency was mainly due
      to the strong adsorption by granular sludge, and the biological degradation of
      chlorobenzene was not obvious.

PMID- 12800672
TI  - [Advanced electrochemical oxidation process for treatment of biorefractory
      wastewater containing typical aromatic compounds].
AB  - Biorefractory wastewater containing one kind of typical aromatic compounds, i.e.,
      aniline, chlorobenzene, p-chlorophenol and p-nitrophenol, was investigated by
      Advanced Electrochemical Oxidation Process (AEOPs) on a novel beta-PbO2 anode
      modified by fluorine resin. Under current of 0.25A, the removal rate for organic
      compounds and COD of the wastewater in 2 hours was around 75%-100%, and 22%-55%,
      respectively, following by the sequence of aniline, chlorobenzene, p-chlorophenol
      and p-nitrophenol. Higher current and initial organic compound concentration
      could enhance the wastewater treatment efficiencies. Benzoquinone, fumaric acid
      and oxalic acid were detected as the common degradation intermediates by HPLC,
      based on which a general degradation pathway of these aromatic compounds was
      further proposed.

PMID- 12800673
TI  - [Treatment of wastewater from a toilet for reclamation with a airlift external
      recirculated membrane bioreactor].
AB  - A new type membrane bioreactor(MBR) coupled with a separated immersed membrane
      unit was studied for treatment of wastewater from a toilet and for reclamation of
      the treated water. The results showed that the effluent of the MBR was stable
      with COD < 47 mg/L, BOD5 < 8.5 mg/L, NH3-N < 20 mg/L, when the influent
      concentration was COD 440-970 mg/L, BOD5 307-612 mg/L, NH3-N 59-111 mg/L. The
      treated water could meet the standard of reused water for toilet washing issued
      by the Ministry of Construction P.R. China. The sludge loading, volume loading,
      HRT and their impaction to COD of effluent were studied. Appropriate sludge
      loading, volume loading were respectively 0.1 kg/(kg.d), 1 kg/(m3.d) and HRT 7-8
      hour. The effect of mixed liquid suspendend solid(MLSS), temperature and
      permeating time of the MBR to the membrane fluxes were discussed in this paper.

PMID- 12800674
TI  - [Study on two stage immerged biological film wastewater treatment reactor].
AB  - The two stage immerged biological film wastewater treatment reactor was studied
      in different organic loads. The organic removal efficiency of each stage, filter
      capability and technical contrast between one stage reactor and two stages
      reactor were discussed. The results showed that the distribution ratio of organic
      removal were 76% and 24% in first and second stage reactors respectively, COD
      removal efficiency was 42% in sand filter unit, and the two stage reactor was
      more effective and reliable than one stage reactor in the same organic loads.

PMID- 12800675
TI  - [Screening of high efficiency succinonitrile degrading bacterium strains and
      their degradability].
AB  - Succinonitrile used as a sole source of carbon and nitrogen, two bacterium
      strains, named as J-1-3 and J-13-1, which had high degrading capacity for
      succinonitrile were isolated and screened out from acrylic fiber wastewater and
      biofilm in its treatment structure. Through morphological and biochemical method,
      the two strains were primarily identified as Pseudomonas spp. By tests in shaking
      flasks, it was determined that the strains can be optimum growth at 30 degrees C,
      with shaker rotary speed which indirectly reflected aeration capacity at 250
      r/min, inoculum amount of 0.1%, and initial pH6. On the optimum conditions for
      growth, the degradation experiments on different initial concentrations of
      succinonitrile were carried out. The results indicate that the two strains,
      especially J-13-1 had high degrading efficiency for succinonitrile. With the
      initial concentration of succinonitrile at ca. 6000, 8000 and 10,000 mg/L, the
      degrading rates of succinonitrile by strain J-13-1 reached to 100% after 12.5 h,
      14 h and 16 h, respectively.

PMID- 12800676
TI  - [The action of different kinds of ions on free radical reaction induced by Vc in
      rat liver homogenate].
AB  - The value of OD532 nm of malondialdehyed(MDA) formed by lipid peroxidation was
      used as an indirect index of reaction of free radicals. The roles of Hg2+, Mn2+,
      Ni2+, Cd2+, Cr3+, SeO3(2-) and water solution of As2O3 in vitro system of
      ascorbic acid producing free radicals were studied. The results indicated that
      Mn2+ and Cr3+ inhibited free radicals induced by ascorbic acid but on the
      contrary, Hg2+, Cd2+ and As2O3 showed an enhancing effect, and the roles of Ni2+,
      SeO3(2-) were ambiguous.

PMID- 12800677
TI  - [Removal efficiency of dioxins in flue gas from MSW incineration by using bag
      house and activated carban filter/adsorbor].
AB  - This paper study the removal efficiency of dioxins in the flue gas from small
      scale MSW incinerator, by using bag house, activated carban filter/adsorbor, and
      the combined unit of the bag house and activated carban filter/adsorbor. The
      removal efficiencies of the above three units respectively were 39.7%, 61.9%,
      93.4% at 850-900 degrees C. It was shown that the combined unit of the bg house
      and activated carban filter/adsobor could reduce the operation cost, as well as
      meet the national criterion.

PMID- 12800678
TI  - [Co-composting of high moisture vegetable waste, flower waste and chicken litter
      in pilot scale].
AB  - Co-composting of different mixture made of vegetable waste, flower waste and
      chicken litter were studied. The first stage of composting was aerobic static bed
      based temperature feedback and control via aeration rate regulation. The second
      stage was window composting. At first stage, the pile was insulated and
      temperatures of at least 55 degrees C were maintained for a minimum of 3 days.
      The highest temperature was up to 73.3 degrees C. This is enough to kill
      pathogens. Moisture of pile decreased from 75% to 56% and organic matter was
      degraded from 65% to 50% during composting. The value of pH was stable at 8.
      Analysis of maturity and nutrition of compost showed that end-products of
      composting ware bio-stable and had abundant nutrition. This shows that co
      composting of vegetable waste, flower waste and chicken litter can get high
      quality compost by optimizing composting process during 45 days. Composting can
      decrease nonpoint resource of organic solid waste by recycling nutrition to soil
      and improve fertility of soil.

PMID- 12800679
TI  - [The variation of inoculation complex microbial community in three stages MSW
      composting process controlled by temperature].
AB  - Adding inoculation agent is one of the effective methods to accelerate the
      composting process of municipal solid wastes. However, because of the competing
      of indigenous microorganisms, high concentration of existing indigenous
      microorganisms could inhibit the prevalence of inoculating microorganisms. When
      indigenous microorganisms concentration in the raw material was 4 x 10(8) CFU/g,
      the microorganisms of inoculating did not grow up. With the process, the
      microbial population of inoculation declined rapidly and no-inoculating microbial
      population rose up quickly and reached a peak of 10(10) CFU/g. When indigenous
      microorganisms concentration was 4 x 10(5) CFU/g, the microorganisms of
      inoculation could inhibit the prevalence of the indigenous microorganisms and
      inoculating microbial population increased quickly and reached a peak of 10(11)
      CFU/g. Therefore, this paper introduces a method of three stages composting
      technology, which combined the heat produced from composting system and some
      extra energy, and heated up the composting temperature above 75 degrees C in 4
      hours as well as maintaining for 8 hours. It well controlled the concentration of
      the indigenous microorganisms under 4 x 10(5) CFU/g and improve the structure of
      the compost media and make the remaining solids more amenable to biological
      attack. When composting materials temperature drops to 35 degrees C to 45 degrees
      C, add complex microorganisms in composting process. Then they develop more
      quickly than the others, the concentration of them rose up from 10(8) CFU/g to
      10(11) CFU/g and lie in a preponderate position. So with this method, advanced
      the rate of organic degradation in municipal solid wastes (MSW) composting
      process, and enhanced the numbers of inoculation microorganisms in composting
      products. Therefore, they can be as inoculation agent for improving composting
      conditions, speedup the next composting process, cutting down the composting
      time, saving original inoculation agent and making composting more economic. But
      using compost products as inoculum, with the number of feedback increasing, the
      concentration ratio of inoculation microorganisms and no-inoculation
      microorganisms is around 1:3 (fifth feedback compost products). So, the number of
      feedback compost products should not be more than five.

PMID- 12800680
TI  - [Effect of adding amendments on preserving nitrogen during chicken manure and saw
      composting].
AB  - In the automatic aerobic compost device, experiments were carried out to
      investigate the effect of four amendments on inhibition of nitrogen losses during
      the chicken manure and saw composting. The changes of chemical parameters,
      temperature, pH, water soluble ammonium and organic nitrogen, total nitrogen and
      organic carbon with time during the aerobic composting process were investigated.
      The results suggested that adding four amendments have certain effect on preserve
      nitrogen and chemical parameters. Treatments added different amendments all
      decreased the nitrogen losses and increased the decomposition of organic carbon
      for 40 days-composting. The effect extent of four amendments was adding peat and
      superphosphate together > adding peat > adding superphosphate > adding zeolite.
      Especially adding peat and superphosphate together prolonged the high temperature
      stage 5 days, decreased the pH 0.89 pH unit in the initial stage and 0.44 pH unit
      in the high temperature stage during composting, and it decreased the nitrogen
      losses about 65.1% during the composting.

PMID- 12800681
TI  - Strategies for integrating Medicare and Medicaid: design features and incentives.
AB  - In a typical third-party payer situation--representative of most U.S. health care
      delivery--the payer is likely to have interests that are at odds with the patient
      and provider. The separation and overlap between Medicare and Medicaid for
      individuals eligible for both programs introduces an additional level of
      complexity: multiple masters over plans, providers, and patients. This creates
      opportunities for shifting costs and administrative burdens between states and
      the federal government, providers and governments, and patients and everyone
      else. Program designers who wish to minimize unwanted consequences must find ways
      to structure their programs to produce financial incentives that encourage the
      pursuit of societal goals, including appropriately shared intergovernmental
      responsibilities and appropriate plan, provider, and patient behavior. Here the
      authors review nine federal and state initiatives that use varying strategies to
      integrate Medicare and Medicaid services for vulnerable populations. For each
      initiative, the authors examine and critique program design features in three
      areas: (1) eligibility determination, (2) finance and administration, and (3)
      service delivery. They find a few strengths and many weaknesses in design. Future
      efforts would be well served by carefully considering the incentive structures
      designed into these initiatives and working to improve them in the next
      generation of Medicare-Medicaid integration efforts.

PMID- 12800682
TI  - The association between three different measures of health status and
      satisfaction among patients with diabetes.
AB  - Studies suggest that health status influences patient satisfaction, but little
      work has examined the influence of different measures of health status on
      satisfaction. The authors examined whether the association between health status
      and satisfaction varied for different measures of health status among 2000
      diabetic patients receiving care across 25 Veterans Affairs facilities. Health
      status was measured using (1) the diabetes-related components of the Total
      Illness Burden Index (DM TIBI), a measure of diabetes severity and comorbidities;
      (2) the Short Form 36 (SF-36) Physical Function Index (PFI10); and (3) the SF-36
      general health perceptions question (SF-1). Satisfaction was measured both by a 5
      item scale on satisfaction with patient-provider communication and by a single
      item on overall diabetes care satisfaction. In adjusted models, worse health on
      all three health status measures correlated with lower satisfaction, but the DM
      TIBI explained more of the variation in satisfaction than either the PFI10 or SF
      1. Moreover, when the DM TIBI was added to the model containing PFI10, PFI10 was
      no longer significantly associated with satisfaction. In this diabetes
      population, health status appears to have a substantial impact on patient
      satisfaction, and this effect is considerably greater for diabetes severity than
      for physical functioning.

PMID- 12800683
TI  - Differential adoption of pharmacotherapy recommendations for type 2 diabetes by
      generalists and specialists.
AB  - Newer, multimedication (novel) regimens provide better glycemic control for many
      type 2 diabetics when sulfonylurea monotherapy (traditional) becomes ineffective.
      Because better glycemic control is associated with decreased likelihood of
      complications and lower utilization and cost of care, the authors examined change
      in prescribing patterns for veterans with type 2 diabetes between FY 97 and 99.
      They classified medication regimens as traditional and novel based on the
      combination of diabetes medications patients received at the end of each year.
      Multivariate logistic regression analyses controlling for disease severity
      indicated that patients were more likely to receive novel regimens over time, but
      those seen only in primary care were less likely to receive novel regimens than
      those previously seen by a specialist. Geographic differences and differences in
      how recommendations were implemented by generalists and specialists suggest that
      diffusion of innovations theory may help explain variations in practice and guide
      interventions designed to translate research into practice.

PMID- 12800684
TI  - Medicare maximization by state Medicaid programs: effects on Medicare home care
      utilization.
AB  - Medicaid programs in some states have attempted to shift home health care costs
      to Medicare by using retrospective billing practices. The authors explored
      whether retrospective billing practices increase Medicare utilization for dual
      eligibles by analyzing primary data on the existence of retrospective billing
      practices collected from 47 state Medicaid offices complemented with individual
      level secondary data from the 1992-1997 Medicare Current Beneficiary Survey. An
      individual-level random effects model was used to estimate the increase in the
      probability and amount of Medicare home care visits from state retrospective
      billing practices. Retrospective billing practices were found not to affect
      either the probability or the amount of Medicare home care visits in these data,
      but the significant inverse relationship found between Medicaid and Medicare
      visits shows that states with high Medicaid utilization have opportunity to shift
      some of these visits to Medicare.

PMID- 12800685
TI  - Searching for and selecting a nursing facility.
AB  - In this study, the authors present findings from 306 resident interviews matched
      with 306 family member interviews examining factors associated with both the
      search for and selection of a nursing facility. For many elders transitioning
      into a nursing facility, the facility becomes their home, and the average cost of
      residing in that home is high. As such, searching for and selection of a facility
      has important consequences. The authors found that residents are not very
      influential in these processes. Second, they found very few proactive nursing
      facility choices were made by either residents or family members. Third, the
      choices made were seldom based on the quality of the facility. Fourth, prior
      knowledge of the chosen facility was limited. Finally, the authors also show that
      the time taken to choose a facility was in most cases extremely limited.

PMID- 12800686
TI  - VHA enrollees' health care coverage and use of care.
AB  - The authors examined health care coverage for Veterans' Health Administration
      (VHA) enrollees and how their reliance on VHA care varies by coverage, using the
      largest and most detailed survey of veterans using VHA services ever conducted.
      The results showed that a majority of veterans who use VHA services have
      alternative health care coverage and that most of them use both VHA and non-VHA
      health care. The findings have important implications for quality of care and
      coordination of care.

PMID- 12800687
TI  - Sicker and poorer--the consequences of being uninsured: a review of the research
      on the relationship between health insurance, medical care use, health, work, and
      income.
AB  - Health services research conducted over the past 25 years makes a compelling case
      that having health insurance or using more medical care would improve the health
      of the uninsured. The literature's broad range of conditions, populations, and
      methods makes it difficult to derive a precise quantitative estimate of the
      effect of having health insurance on the uninsured's health. Some mortality
      studies imply that a 4% to 5% reduction in the uninsured's mortality is a lower
      bound; other studies suggest that the reductions could be as high as 20% to 25%.
      Although all of the studies reviewed suffer from methodological flaws of varying
      degrees, there is substantial qualitative consistency across studies of different
      medical conditions conducted at different times and using different data sets and
      statistical methods. Corroborating process studies find that the uninsured
      receive fewer preventive and diagnostic services, tend to be more severely ill
      when diagnosed, and receive less therapeutic care. Other literature suggests that
      improving health status from fair or poor to very good or excellent would
      increase both work effort and annual earnings by approximately 15% to 20%.

PMID- 12800688
TI  - The low-down on low-carbohydrate diets.

PMID- 12800689
TI  - A small contribution to the nursing shortage.

PMID- 12800690
TI  - Legislative editorial encourages NPs.

PMID- 12800691
TI  - Legislative editorial encourages NPs.

PMID- 12800692
TI  - Differentiate depression from dementia.
AB  - Depression and dementia are two common problems among the elderly that may be
      difficult to differentiate. Prompt and accurate diagnosis is important not only
      for symptom management, but to reduce social isolation and cognitive impairment,
      and prevent physical disability and suicide. Use this six-step process as a
      guideline to help differentiate depression and dementia.

PMID- 12800693
TI  - Annual update: drugs, diagnostics and devices.
AB  - As NPs continue to play an important role in health care as administers of
      prescriptions, the value of reviewing the latest Food and Drug Administration
      (FDA) approvals for new drugs and devices is immeasurable. In 2002, the FDA
      approved several new drugs and devices, as well as monitored previously approved
      drugs for adverse reactions and untoward events. This article provides a brief
      review of relevant primary care topics.

PMID- 12800694
TI  - Financially viable nurse-managed centers.
AB  - Nurse managed centers play an important role in the health service delivery
      system; often serving those in greatest need, while struggling to remain
      financially viable. This article discusses the role of a Financial Advisory
      Committee (FAC) and the process of financial peer review in academic nurse
      managed centers to improve financial outcomes. Advanced practice nurses may find
      the identified strategies for financial sustainability useful in their own
      practices.

PMID- 12800695
TI  - NP errors lead to litigation.

PMID- 12800696
TI  - Guillain-Barre: a case of muscular weakness and ambulatory difficulty.

PMID- 12800697
TI  - FDA-approved home HIV test available nationwide.

PMID- 12800698
TI  - Warn patients of imported drug dangers.

PMID- 12800699
TI  - Integration of sexual and reproductive health services: a health sector priority.

PMID- 12800700
TI  - Low use of rural maternity services in Uganda: impact of women's status,
      traditional beliefs and limited resources.
AB  - In Uganda, lack of resources and skilled staff to improve quality and delivery of
      maternity services, despite good policies and concerted efforts, have not yielded
      an increase in utilisation of these services by women or a reduction in the high
      ratio of maternal deaths. This paper reports a study conducted from November 2000
      to October 2001 in Hoima, a rural district in western Uganda, whose aim was to
      enhance understanding of why, when faced with complications of pregnancy or
      delivery, women continue to choose high risk options leading to severe morbidity
      and even their own deaths. The findings demonstrate that adherence to traditional
      birthing practices and beliefs that pregnancy is a test of endurance and maternal
      death a sad but normal event, are important factors. The use of primary health
      units and the referral hospital, including when complications occur, was
      considered only as a last resort. Lack of skilled staff at primary health care
      level, complaints of abuse, neglect and poor treatment in hospital and poorly
      understood reasons for procedures, plus health workers' views that women were
      ignorant, also explain the unwillingness of women to deliver in health facilities
      and seek care for complications. Appropriate interventions are needed to address
      the barriers between rural mothers and the formal health care system, including
      community education on all aspects of essential obstetric care and sensitisation
      of service providers to the situation of rural mothers.

PMID- 12800701
TI  - Integration of post-abortion care: the role of township medical officers and
      midwives in Myanmar.
AB  - Complications of unsafe abortion are a significant cause of maternal morbidity
      and mortality in Myanmar, and are recognised by the Ministry of Health as a
      priority. The Department of Health developed a strategy to address the problem of
      abortion complications by integrating post-abortion care and contraceptive
      services into the existing township health system. The quality of post-abortion
      care was assessed by the Department of Health in 2000, using a baseline survey of
      health providers and post-abortion women in Bago Division. The integration of
      post-abortion care was led by the Township Medical Officers, who provided monthly
      in-service training and supervision of health care workers in each township.
      Hospital-based doctors and nurses, clinic midwives, village midwives and other
      volunteer health providers, including traditional birth attendants, were all
      trained. The role of the local clinic midwife was extended to make follow-up home
      visits to the women with post-abortion complications and provide them with
      contraception when requested. Preliminary results show positive outcomes.
      However, donor-funded projects may have a destabilizing effect on township
      services by diverting attention and resources; donors need to work with
      government to support its priorities for health care. The future nationwide
      integration of post-abortion care services into township services should be
      planned in consultation with Township Medical Officers and midwives, the key
      providers of these services.

PMID- 12800702
TI  - Integrating reproductive health services in a reforming health sector: the case
      of Tanzania.
AB  - Universal access to comprehensive reproductive health services, integrated into a
      well-functioning health system, remains an unfulfilled objective in many
      countries. In 2000-2001, in Tanzania, in-depth interviews were conducted with
      central level stakeholders and focus group discussions held with health
      management staff in three regional and nine district health offices, to assess
      progress in the integration of reproductive health services. Respondents at all
      levels reported stalled integration and lack of synchronisation in the planning
      and management of key services. This was attributed to fear of loss of power and
      resources among national level managers, uncertainty as to continuation of donor
      support and lack of linkages with the Health Sector Reform Secretariat. Among
      reproductive health programmes, sexually transmitted infection (STI) control
      alone retained its vertical planning, management and implementation structures.
      District-level respondents expressed frustration in their efforts to coordinate
      STI service delivery with other, more integrated programmes. They reported
      contradictory directives and poor communication channels with higher levels of
      the Ministry of Health; lack of technical skills at district level to undertake
      supervision of integrated services; low morale due to low salaries; and lack of
      district autonomy in decision-making. Integration requires a coherent policy
      environment. The uncoordinated and conflicting agendas of donors, on whom
      Tanzania is too heavily reliant, is a major obstacle.

PMID- 12800703
TI  - Incorporating sexual and reproductive health care in the medical curriculum in
      developing countries.
AB  - Medical educators have a responsibility to train physicians and other health
      professionals in the core competencies needed to improve the sexual and
      reproductive health of their communities. Yet sexual and reproductive health care
      is significantly under-represented in the basic educational curriculum for
      medical and other health professionals, as well as in continuing medical
      education and professional development programmes for practising physicians and
      other health professionals. The Commonwealth Medical Association Trust is
      developing a model curriculum on sexual and reproductive health that can be
      integrated into undergraduate medical education and used with appropriate
      amendments for continuing medical education. This paper outlines topics for
      inclusion in the curriculum and three strategies for incorporating core
      components of sexual and reproductive health in the curriculum--by developing
      themes that can be integrated into the general curriculum in a multi-disciplinary
      fashion, adding free-standing modules as electives, and delegating cross-cutting
      issues such as gender issues and adolescent reproductive health to courses run by
      other departments. It argues for the use of problem-solving and case-based
      learning methodologies, as well as lectures, as the best way to teach health
      professionals how to provide information, counselling and support for sexual and
      reproductive health, as well as to cover the range of prevention and treatment
      needs of women and men seeking these services.

PMID- 12800704
TI  - Reproductive health care in The Netherlands: would integration improve it?
AB  - Since the 1994 ICPD, relatively little attention has been given to constraints in
      improving reproductive health programmes in industrialised countries. The
      Netherlands is known for its low rates of unwanted pregnancy, safe and accessible
      abortion services, low perinatal and maternal mortality and well-developed
      programmes for adolescent sexual health, but recent studies show a rising
      incidence of abortions and STDs, particularly among young people and immigrants.
      This article describes reproductive health services in the Netherlands, their
      historical roots and current constellation, including services for family
      planning, abortion, STDs, infertility, information, education and counselling on
      sexuality, and antenatal and delivery care, in the context of cost containment
      and other recent reforms. It shows that although these core components are well
      covered and the system of reimbursement for costs has greatly helped to increase
      accessibility, they are not all well integrated into the primary health care
      system. In some cases, they are well covered by other providers, such as
      midwives. Prevention and management of STDs and infertility, however, are
      particularly split between different providers and in some cases the extent and
      quality of service provision is lacking. What emerges is a still fragmented
      landscape--with many successes but also some significant shortcomings.

PMID- 12800705
TI  - The impact of decentralisation on sexual and reproductive health services in
      Ghana.
AB  - This paper analyses the impact of decentralisation on the political organisation,
      management and provision of sexual and reproductive health services in Ghana. It
      draws on qualitative research and interviews with key informants from the
      Ministry of Health, donors, NGOs, regional and district health management teams,
      local government and community leaders. Within a national reproductive health
      policy framework, previously disparate family planning, maternal and child
      health, STI and HIV/AIDS programmes have become more integrated, and donors have
      pooled or co-ordinated their funding. Some decision-making about resource
      allocation is meant to happen at district and regional level but in practice,
      this remains centrally controlled, which may be a necessary safeguard for sexual
      and reproductive health services. Earmarked donor funds still ensure a regular
      supply of contraceptives and STI drugs. However, paying for these is problematic
      at local level. Sexual and reproductive health staff make up a large proportion
      of primary health care staff, but especially in rural areas they experience poor
      working conditions, and there is high turnover and vacancies. District and sub
      district level links are working well in this new system, but clarity is still
      needed on how different national sexual and reproductive health bodies relate to
      each other and to regional and district health authorities. The development of
      formal mechanisms for priority setting and advocacy at local levels could help to
      secure benefits for sexual and reproductive health care.

PMID- 12800706
TI  - The need for family planning and safe abortion services among women sex workers
      seeking STI care in Cambodia.
AB  - In Cambodia, clinics established for the prevention and management of sexually
      transmitted infections (STIs) in women sex workers do not address other
      reproductive health services. The aim of this study was to assess the need for
      more comprehensive sexual and reproductive health services for women sex workers
      in Cambodia. In January 2000, relevant documents were reviewed, interviews with
      key informants carried out and group interviews with women sex workers conducted.
      Medical records from women sex workers were also reviewed and some data collected
      prospectively in one government STI clinic. Interviews with the women and data
      from the government clinic indicated that excluding condoms, a very low
      proportion of women sex workers were currently using a modern contraceptive
      method--5% of 38 women and 1.6% of 632 women, respectively. Induced abortion was
      widely used but was perceived to be risky and costly. Data from a mobile team
      intervention and the government clinic respectively showed that 25.5% (n = 1744)
      and 21.9% (n = 588) of women sex workers reported at least one previous induced
      abortion. These findings reveal the need for accessible contraception and safe
      abortion services among sex workers in Cambodia, and raise the issue of the
      reproductive rights and reproductive health needs of women sex workers in
      general.

PMID- 12800707
TI  - Decentralisation and its implications for reproductive health: the Philippines
      experience.
AB  - Decentralisation is one of the most common health sector reforms initiated in
      developing countries in the 1980-90s. Although decentralisation is often
      politically driven, it can significantly improve health sector performance.
      However, the early phase of the Philippines experience indicates that
      decentralisation in and of itself does not always improve the efficiency, equity
      and effectiveness of the health sector. Instead, it can exacerbate inequities,
      weaken local commitment to priority health issues and decrease the efficiency and
      effectiveness of service delivery by disrupting the referral chain. Such effects
      pose a particularly serious threat to accessibility and delivery of reproductive
      health services, some of which (e.g. family planning) are controversial and thus
      susceptible to local pressures, and others of which (e.g. emergency obstetric
      care) require a functioning and effective health system. Moreover, those
      undertaking decentralisation need to take account of the impacts of non-health
      factors as well as other reforms that interact with decentralisation to affect
      accessibility, affordability and quality of services, including for reproductive
      health. The Philippines experience also demonstrates that authority should be
      shared between the centre and local units in order to achieve national health
      objectives and respond to local health needs. Adjustments must be made during
      implementation to correct for both emerging and pre-existing problems.

PMID- 12800708
TI  - The human face of decentralisation and integration of health services: experience
      from South Africa.
AB  - This paper explores the processes of policy-making, budgeting and service
      implementation in three provinces of South Africa, drawing on interviews with
      health managers at different levels of government. It illustrates how the process
      of decentralisation creates disjunctures between the policy-making authority of
      higher levels of government and the implementation capacity of service provision
      levels. It also explores the complex dynamics between those responsible for
      specific policies, such as reproductive health policies, and those responsible
      for managing the integrated delivery of all policies, with their resultant
      contestations over authority and resources. The pace of change in South Africa
      and the enormous capacity it requires, both in relation to financial management
      and the technical skills needed for specific programmes, has created a sense of
      frustration and demoralisation. Whilst shortage of financial resources,
      particularly as reflected in shortage of staff, is frequently assumed to be the
      biggest constraint in this context, most managers identified other issues,
      particularly staff morale, as greater barriers to the delivery of high quality
      health services. The paper concludes that it is the complexity of experience and
      feelings described by health managers that may determine the extent and quality
      of service delivery. For this reason, both practice and research need to give
      greater attention to issues of power relations and personal experience of change.

PMID- 12800709
TI  - Sex, studies or strife? What to integrate in adolescent health services.
AB  - If health services for adolescents are to be successfully integrated into the
      existing health care system, they will need to reach out to meet the needs that
      adolescents themselves perceive as salient. This paper describes a study aiming
      to elicit the needs of adolescents in higher secondary schools in Goa, India, in
      1999-2000. The objective was to generate information which could guide the
      development of adolescent-friendly health services by integrating the health
      needs identified by adolescents themselves. The study began with free-listing,
      followed by focus group discussions and in-depth interviews to elicit areas of
      concern. Then, a survey of 811 students with a self-report questionnaire was
      carried out. The findings demonstrate that there is clearly an unmet need for
      information about sexual and reproductive health, but also a large, unmet need
      for psychosocial support for health issues ranging from violence in schools to
      poor relationships with parents, stress-related health complaints and educational
      difficulties, which are often perceived by adolescents to be of primary
      importance. Integrating these issues into programmes is likely to be an essential
      element in developing health services and programmes which can reach out to the
      majority of adolescents in school settings in India.

PMID- 12800710
TI  - Expanding safer sex options: introducing the female condom into national
      programmes.
AB  - Although the female condom has been introduced into over 90 countries since 1997,
      it has only been accepted in sexual and reproductive health programmes as a
      mainstream method in a few. This paper describes introductory strategies
      developed by Ministries of Health and non-governmental organisations in Brazil,
      Ghana, Zimbabwe and South Africa, supported by UNAIDS, and the manufacturers of
      the female condom, which have significantly expanded the number of female condoms
      being used. These projects have several key similarities: a focus on training for
      providers and peer educators, face-to-face communication with potential users to
      equip them with information and skills, an identified target audience, a
      consistent supply, a long assessment period to gauge actual use beyond the
      initial novelty phase, and a mix of public and private sector distribution.
      Female condom programmes require the sanction, leadership and funding of
      governments and donors. However, the non-governmental and private sectors have
      also played a major role in programme implementation. To ensure successful
      introduction of the female condom, it is crucial to involve a range of decision
      makers, programme managers, service providers, community leaders and women's and
      youth groups. The rising cost of inaction and unprotected sex in the spread of
      HIV and AIDS force us to recognise the high cost of not providing female condoms
      alongside male condoms in family planning and AIDS prevention programmes.

PMID- 12800711
TI  - Implementing reproductive and child health services in rural Maharashtra, India:
      a pragmatic approach.
AB  - The Government of India has been providing limited maternal and child health
      services through its Family Welfare programme, but this system is characterised
      by weaknesses that include inefficient work schedules; non-availability of
      functioning equipment; poor contraceptive and drug supplies; poor skills and
      knowledge of health workers; and poor access to services in villages without
      health centres. For the new Reproductive and Child Health programme to deliver an
      even wider range of services, the health system will need to be strengthened and
      the quality of service delivery improved. This paper describes a seven-year
      operations research project in Parner block, Ahmednagar district, Maharashtra,
      India, undertaken by the Foundation for Research in Health Systems in partnership
      with state and district health administrations. It shows the feasibility of
      establishing a more efficient system, with a minimum of affordable inputs, that
      increases the use of services by women. Four critical policy changes were
      implemented: service delivery in each village was changed from household visits
      to a clinic base, stringent monitoring mechanisms were put in place, in-service
      training for health workers was instituted and the range of services was
      gradually increased. This experience is now being applied more widely, with
      eventual phasing up to full district and state level.

PMID- 12800712
TI  - Expanding access to emergency contraception: the case of Brazil and Colombia.
AB  - Emergency contraception was proven effective nearly 30 years ago yet remains
      greatly under-utilised. In the Latin American and Caribbean region, it would
      serve the goals of reducing unwanted pregnancy, unsafe abortion and related
      morbidity, and as a back-up to condom use and a bridge to longer-term
      contraceptive methods if made more widely known and available. The International
      Planned Parenthood Federation Western Hemisphere Region has developed a model for
      the integration of emergency contraception into sexual and reproductive health
      care services. This model is being tested in a two-year project with national
      affiliates in Brazil, Chile, Colombia, the Dominican Republic and Venezuela, and
      will contribute to the work of the Latin American Consortium for Emergency
      Contraception. Case studies of Brazil and Colombia describe how health sector
      reforms, e.g. decentralisation and managed competition among health insurers and
      service providers, have influenced promotion strategies. The experience of
      Profamilia Colombia with registration of a dedicated product and providing
      emergency contraception within its national network of clinics, with a focus on
      staff training and work with young people, is described. In Brazil, BEMFAM's
      study of different modalities for offering emergency contraception, e.g. through
      contractual agreements with municipalities and its own clinics, is highlighted.

PMID- 12800713
TI  - Using accountability to improve reproductive health care.
AB  - Accountability is best understood as a referee of the dynamics in two-way
      relationships, often between unequal partners. The literature on accountability
      distinguishes between political, fiscal, administrative, legal and constitutional
      accountability. This paper focuses on accountability mechanisms in health care
      and how they mediate between service providers and communities and between
      different kinds of health personnel at the primary health care level. It refers
      to case studies of participatory processes for improving sexual and reproductive
      health service delivery. Information, dialogue and negotiation are important
      elements that enable accountability mechanisms to address problems by supporting
      change and engagement between participants. In order to succeed, however, efforts
      towards better accountability that broaden the participation of users must take
      into account the social contexts and the policy and service delivery systems in
      which they are applied, address power relations and improve the representation of
      marginalised groups within communities and service delivery systems.

PMID- 12800714
TI  - A framework for developing reproductive health policies and programmes in Nepal.
AB  - Based on experience in Nepal from 1996-2001, this paper presents a six-element
      framework to support governments in poor countries in developing and implementing
      reproductive health programmes. The six elements of the framework are: (i)
      collaborative planning and programming; (ii) strategic assessment; (iii) policy
      and strategy development; (iv) guideline and material development; (v)
      reproductive health programme management; and (vi) policy review. Its
      implementation calls for collaborative work between policymakers and programme
      managers at all levels of the health system, external donors and development
      agencies. Change in Nepal is constrained by poor human and financial resources,
      extremely difficult geography and strong cultural, religious and social
      traditions. An informal assessment at district level and below found that
      information tools, clinical protocols and operational guidelines were highly
      relevant, though problems with utilisation and motivation were noted. Utilisation
      of strategy and policy documents and tools was reported to be high at national
      level, but no causal link can be drawn between instruments in the framework and
      changes in reproductive health indicators. However, access to the tools described
      in this article can contribute to improvements in coverage and quality of
      reproductive health services in the hands of motivated people; improved
      indicators in family planning use, antenatal care and assisted delivery in Nepal
      in this period support this view.

PMID- 12800715
TI  - Restructuring the health system: experiences of advocates for gender equity in
      Bangladesh.
AB  - This paper illustrates how advocates for gender equity succeeded in influencing
      the restructuring of the health system in Bangladesh in the mid-1990s but failed
      to influence its implementation. Using published and unpublished documents and
      personal interviews, it traces the changing fortunes of health sector reforms and
      reform advocates from 1995 to 2002 and analyses the major challenges and
      strategies involved. It explores the gains advocates for gender equity made in
      the design of the reforms and also their limitations to counter some of the
      inherent risks. The paper highlights the gaps between the design and
      implementation of reforms. It argues that the key factor for success during the
      design of reforms was the participation of civil society, which enabled a large
      number of women, particularly poor women, to engage with the design of reforms.
      During the implementation phase, however, reforms became a government-donor
      driven programme disconnected from civil society and space for women's voices
      became limited. When a new government assumed power in 2001, opponents of reform
      succeeded in halting the restructuring of the health system, in part because
      civil society was no longer engaged with the reform process and registered little
      protest.

PMID- 12800716
TI  - Storytelling that moves people. A conversation with screenwriting coach Robert
      McKee.
AB  - When executives need to persuade an audience, most try to build a case with
      facts, statistics, and some quotes from authorities. In other words, they resort
      to "companyspeak," the tools of rhetoric they have been trained to use. In this
      conversation with HBR, Robert McKee, the world's best-known screenwriting
      lecturer, argues that executives can engage people in a much deeper--and
      ultimately more convincing--way if they toss out their Power-Point slides and
      memos and learn to tell good stories. As human beings, we make sense of our
      experiences through stories. But becoming a good storyteller is hard. It requires
      imagination and an understanding of what makes a story worth telling. All great
      stories deal with the conflict between subjective expectations and an
      uncooperative objective reality. They show a protagonist wrestling with
      antagonizing forces, not a rosy picture of results meeting expectations--which no
      one ends up believing. Consider the CEO of a biotech start-up that has discovered
      a chemical compound to prevent heart attacks. He could make a pitch to investors
      by offering up market projections, the business plan, and upbeat, hypothetical
      scenarios. Or he could captivate them by telling the story of his father, who
      died of a heart attack, and of the CEO's subsequent struggle against various
      antagonists--nature, the FDA, potential rivals--to bring to market the effective,
      low-cost test that might have prevented his father's death. Good storytellers are
      not necessarily good leaders, but they do share certain traits. Both are self
      aware, and both are skeptics who realize that all people--and institutions--wear
      masks. Compelling stories can be found behind those masks.

PMID- 12800717
TI  - Leadership and the psychology of turnarounds.
AB  - Turnaround champions--those leaders who manage to bring distressed organizations
      back from the brink of failure--are often acclaimed for their canny financial and
      strategic decision making. But having studied their work closely, Harvard
      Business School's Rosabeth Moss Kanter emphasizes another aspect of their
      achievement. These leaders reverse the cycle of corporate decline through
      deliberate interventions that increase the level of communication, collaboration,
      and respect among their managers. Ailing companies descend into what Kanter calls
      a "death spiral," which typically works this way: After an initial blow to the
      company's fortunes, people begin pointing fingers and deriding colleagues in
      other parts of the business. Tensions rise and collaboration declines. Once they
      are no longer acting in concert, people find themselves less able to effect
      change. Eventually, many come to believe they are helpless. Passivity sets in.
      Finally, the ultimate pathology of troubled companies takes hold: denial. Rather
      than volunteer an opinion that no one else seems to share, people engage in
      collective pretense to ignore what they individually know. To counter these
      dynamics, Kanter says, and reverse the company's slide, the CEO needs to apply
      certain psychological interventions--specifically, replacing secrecy and denial
      with dialogue, blame and scorn with respect, avoidance and turf protection with
      collaboration, and passivity and helplessness with initiative. The author offers
      in-depth accounts of how the CEOs at Gillette, Invensys, and the BBC used these
      interventions to guide their employees out of corporate free fall and onto a more
      productive path.

PMID- 12800718
TI  - M&A needn't be a loser's game.
AB  - Three out of four acquisitions fail; they destroy wealth for the buyer's
      shareholders, who end up worse off than they would have been had the deal not
      been done. But it doesn't have to be that way, argue the authors. In evaluating
      acquisitions, companies must look beyond the lure of profits the income statement
      promises and examine the balance sheet, where the company keeps track of capital.
      It's ignoring the balance sheet that causes so many acquisitions to destroy
      shareholders' wealth. Unfortunately, most executives focus only on sales and
      profits going up, never realizing that they've put in motion a plan to destroy
      their company's true profitability--its return on invested capital. M&A, like
      other aspects of running a company, works best when seen as a way to create
      shareholder value through customers. Some deals are sought to help create better
      value propositions for the business or to better execute current strategies--or
      to block competitors from doing these things. But most deals are about customers
      and should start with an analysis of customer profitability. Some customers are
      deliciously profitable; others are dismal money losers. The better an acquirer
      understands the profitability of its own customers, the better positioned it will
      be to perform such analyses on other companies. In this article, the authors show
      that customer profitability varies far more dramatically than most managers
      suspect. They also describe how to measure the profitability of customers. By
      understanding the economics of customer profitability, companies can avoid making
      deals that hurt their shareholders, they can identify surprising deals that do
      create wealth, and they can salvage deals that would otherwise be losers.

PMID- 12800720
TI  - Let's hear it for B players.
AB  - In the much-heralded war for talent, it's hardly surprising that companies have
      invested a lot of time, money, and energy in hiring and retaining star
      performers. For most CEOs, recruiting stars is simply more fun; for one thing,
      the young A players they interview often remind them of themselves at the same
      age. For another, A players' brilliance and drive is infectious; you simply want
      to be in their company. Besides, in these troubled times, when businesses are so
      vulnerable, people who seem to have what it takes to turn around a company's
      performance are almost irresistible. But our understandable fascination with star
      performers can lure us into the dangerous trap of underestimating the vital
      importance of the supporting actors. It's true that A players can make enormous
      contributions to performance. Yet, as the authors have found, companies' long
      term performance--even survival--depends far more on the unsung commitment and
      contributions of their B players. These capable, steady performers are the best
      supporting actors of the corporate world. Companies are routinely blinded to the
      important role B players serve in saving organizations from themselves. They
      counter-balance the ambitions of the company's high-performing visionaries, whose
      much-esteemed strengths, when carried to an extreme, can lead to reckless or
      volatile behavior. In this sense, B players act as a stabilizing force for
      charismatic A players who might otherwise destabilize the organization.
      Unfortunately, organizations rarely learn to value their B players in ways that
      are gratifying for either the company or these employees. As a result, they see
      their profits sinking without understanding why. This article will help you to
      rethink the role of your organization's B players. The authors show how you can
      mentor and nurture B players to ensure their continued participation in the
      company.

PMID- 12800719
TI  - Managing by commitments.
AB  - What makes a great manager great? Despite differences in their personal
      attributes, successful managers all excel in the making, honoring, and remaking
      of commitments. Managerial commitments take many forms, from capital investments
      to personnel decisions to public statements, but each exerts both immediate and
      enduring influence on a company. A leader's commitments shape a business's
      identity, define its strengths and weaknesses, establish its opportunities and
      limitations, and set its direction. Executives can all too easily forget that
      commitments are extraordinarily powerful. Caught up in the present, managers
      often take actions that, while beneficial in the near term, impose lasting
      constraints on their operations and organizations. When market or competitive
      conditions change, they can find themselves unable to respond effectively.
      Managers who understand the nature and power of their commitments can wield them
      more effectively throughout a company's life cycle. Entrepreneurs can avoid
      taking actions that imprint a new venture with a dysfunctional character.
      Managers in established enterprises can buttress past commitments that retain
      their currency and learn to recognize when commitments have become roadblocks to
      needed changes. The manager can then replace those roadblocks with new,
      rejuvenating commitments. That doesn't mean you should try to anticipate all the
      long-run consequences of every commitment--and it certainly doesn't mean you
      should shy away from making commitments. But it does mean that before making
      important decisions about, say, operating processes or partnerships, you should
      always ask yourself: Is this a process or relationship that we can live with in
      the future? Am I locking us into a course that we'll come to regret?

PMID- 12800721
TI  - Pension roulette: have you bet too much on equities?
AB  - In the 1990s, funding pension obligations by investing in stocks looked smart. By
      1999, the bull market had poured a collective $260 billion surplus into the
      pension coffers of the S&P 500, permitting the companies to record the year-to
      year increases as additional income. But just two years later, the bear market
      had obliterated those gains, replacing them with a cavernous $240 billion deficit
      -which had to be offset by the unlucky firms' ongoing cash flows, wreaking havoc
      on their earnings, debt levels, and stock prices. Corporate executives may be
      blamed for this debacle. But they were only following the rules. Current
      accounting guidelines keep companies from recording pension liabilities and
      assets on their balance sheets, instead relegating them to the footnotes. That
      makes it hard to see the risk that market drops expose companies to. Board
      members and top executives need to look beyond distorted accounting numbers to
      the economic realities of pension plans. Once they do, they may be surprised to
      find that they would gain far greater value and flexibility by passively
      investing their pension funds entirely in bonds. A bond portfolio can be designed
      to meet precisely, and with virtual certainty, a company's pension obligation,
      thus eliminating the chance of a funding gap. The predictability of bond
      investments also stabilizes earnings and cash flow. The expanded corporate debt
      capacity that results can then be used to fuel growth or reduce the firm's
      overall cost of capital. Even without an overhaul of today's misguided accounting
      rules, there's little reason for companies' pension funds to hold anything other
      than bonds.

PMID- 12800722
TI  - The myth of secure computing.
AB  - Few senior executives pay a whole lot of attention to computer security. They
      either hand off responsibility to their technical people or bring in consultants.
      But given the stakes involved, an arm's-length approach is extremely unwise.
      According to industry estimates, security breaches affect 90% of all businesses
      every year and cost some $17 billion. Fortunately, the authors say, senior
      executives don't need to learn about the more arcane aspects of their company's
      IT systems in order to take a hands-on approach. Instead, they should focus on
      the familiar task of managing risk. Their role should be to assess the business
      value of their information assets, determine the likelihood that those assets
      will be compromised, and then tailor a set of risk abatement processes to their
      company's particular vulnerabilities. This approach, which views computer
      security as an operational rather than a technical challenge, is akin to a
      classic quality assurance program in that it attempts to avoid problems rather
      than fix them and involves all employees, not just IT staffers. The goal is not
      to make computer systems completely secure--that's impossible--but to reduce the
      business risk to an acceptable level. This article looks at the types of threats
      a company is apt to face. It also examines the processes a general manager should
      spearhead to lessen the likelihood of a successful attack. The authors recommend
      eight processes in all, ranging from deciding how much protection each digital
      asset deserves to insisting on secure software to rehearsing a response to a
      security breach. The important thing to realize, they emphasize, is that
      decisions about digital security are not much different from other cost-benefit
      decisions. The tools general managers bring to bear on other areas of the
      business are good models for what they need to do in this technical space.

PMID- 12800723
TI  - Practical pharmacology. Medication errors.

PMID- 12800724
TI  - The emerging role of pediatric hospitalists.

PMID- 12800725
TI  - Continuing care of NICU graduates.
AB  - After a prolonged and complicated hospital stay, the NICU graduate enters the
      world with unique and complex medical problems. A well-coordinated
      multidisciplinary approach is essential in the follow-up care of these infants.
      The crucial issues for the pediatrician who cares for these infants are assisting
      in the catch-up growth and the ongoing healing process with good nutritional
      supplementation, while preventing further problems by detecting and treating
      illness early. Timely inclusion of other appropriate health care personnel and
      facilities in the care may be crucial and rewarding. The role of the pediatrician
      in helping these infants attain their full physical, neurodevelopmental,
      emotional, and psychosocial potential by providing optimal care is invaluable.
      With appropriate support most NICU graduates will become productive and well
      adjusted adults. The pediatrician plays a major role in completing this process
      and contributes to the eventual success of the neonatal intensive care that these
      infants are subjected to at the very beginning of their lives.

PMID- 12800726
TI  - Accelerated intravenous rehydration.
AB  - This study was undertaken to determine whether accelerated intravenous (i.v.)
      rehydration using a new Isotonic Dehydration Worksheet results in: (1)
      complications in serum sodium or volume status; and (2) decreased duration of
      i.v. fluid therapy or length of hospital stay. A retrospective cohort study
      utilizing chart review method was used. An intervention group of 98 children ages
      1 month to 12 years treated with the Isotonic Dehydration Worksheet from December
      2000 to March 2001 was compared to a control group of 61 children treated from
      December 1999 to March 2000 before introduction of the worksheet. Complication
      rates were low and did not differ between the 2 groups. Mean unadjusted lengths
      of i.v. therapy (35.3 vs. 33.7 hours) and of hospital stay (47.0 vs. 49.3 hours)
      were not significantly different between the 2 groups. Introduction of an
      accelerated rehydration protocol was well tolerated by patients, but did not
      result in a significant decrease in the outcome variables examined. Other factors
      may have a greater impact on the outcome variables, and a prospective study to
      address these questions is planned.

PMID- 12800727
TI  - Adverse drug reactions in breastfed infants: less than imagined.
AB  - Medication use during breastfeeding shortens the duration of breastfeeding often
      because of overly cautious information given by healthcare providers. No
      comprehensive review of the literature on infant adverse reactions from drugs in
      breastmilk has been published. All published studies and case reports on adverse
      events in infants caused by medications (excluding drugs of abuse) in breastmilk
      were identified and analyzed. Of 100 case reports evaluated, none were considered
      to be "definite" using a standard ranking scale; 47% were "probable" and 53% were
      "possible." Drugs with central nervous system activity accounted for half of all
      reports. All 3 reported fatalities involved central nervous system depressants,
      but each had extenuating circumstances. At least 63% of reported cases were in
      neonates and 78% were in infants 2 months or younger; only 4% of adverse
      reactions occurred in infants older than 6 months of age. Published studies
      expand on and generally reinforce the analysis of case reports. By taking a few
      simple precautions in drug selection and considering the infant's age,
      breastfeeding rarely needs to be discouraged or discontinued when a mother needs
      drug therapy.

PMID- 12800728
TI  - Abdominal pain associated with lactose ingestion in children with lactose
      intolerance.
AB  - The causal relationship between lactose ingestion and gastrointestinal symptoms
      is questionable. The aim of this study was to assess symptoms associated with
      milk ingestion in children with lactose maldigestion. Thirty children (11 males)
      age 3 to 17 years with lactose maldigestion were studied. In a double-blind,
      crossover design, subjects ingested 240 mL daily of either lactose-hydrolyzed or
      lactose-containing milk for 14 days. Diaries were kept daily that recorded diet,
      medication use, and symptoms. There was a significant increase in abdominal pain
      experienced by study participants during the lactose ingestion period when
      compared to the lactose-free period. We conclude that ingestion of 12 g of
      lactose daily is associated with increased abdominal pain in susceptible children
      with lactose maldigestion. A trial of dietary lactose restriction may be
      beneficial in reducing abdominal pain in children with lactose maldigestion.

PMID- 12800729
TI  - Clostridium difficile-associated diarrhea in a pediatric hospital.
AB  - This retrospective cohort analysis examined the risk factors, symptoms, and
      severity of disease associated with C. difficile in pediatric inpatients. Risk
      factors for a C. difficile-positive test were an oncologic diagnosis, diarrhea of
      more than 2 days' duration, and gastrointestinal symptoms, especially abdominal
      pain. Over a 3.5-year period, there was a total of 22 C. difficile-positive
      patients, and most had mild, self-limiting diarrheal illness. No cases of C.
      difficile diarrhea were identified. Seventy-eight percent of the C. difficile
      positive patients were found to have alternate risk factors for diarrhea. Our
      data indicate that C. difficile rarely causes severe diarrhea in pediatric
      inpatients and that C. difficile testing should be limited to patients with
      severe prolonged diarrhea and abdominal pain.

PMID- 12800730
TI  - Vertebral fractures in boys with Duchenne muscular dystrophy.
AB  - Osteoporosis causes significant morbidity for boys with Duchenne muscular
      dystrophy. Corticosteroid therapy given to prolong mobility may increase the rate
      of osteoporosis and risk of fracture. This study of 33 boys with Duchenne
      muscular dystrophy determined retrospectively the incidence of vertebral
      fractures particularly after initiation of corticosteroids. A latency period of
      40 months after commencement of steroids occurred before the first vertebral
      fracture appeared. However, by 100 months of treatment approximately 75% had
      sustained a vertebral fracture.

PMID- 12800731
TI  - Comparison of rectal temperature measured by digital vs. mercury glass
      thermometer in infants under two months old.

PMID- 12800732
TI  - Epstein-Barr virus mononucleosis: neurologic complications.

PMID- 12800733
TI  - Congenital hypothyroidism and early severe hyperbilirubinemia.

PMID- 12800734
TI  - Churg-Strauss syndrome: a patient report in infancy.

PMID- 12800735
TI  - Protein-losing enteropathy: an unusual presentation of neuroblastoma.

PMID- 12800736
TI  - Juvenile dermatomyositis in a 28-month-old infant.

PMID- 12800738
TI  - Higher drug copays now might cause problems later.

PMID- 12800737
TI  - A skin defect.

PMID- 12800739
TI  - AWP reimbursement ruling may be more than meets eye.

PMID- 12800740
TI  - Physicians in large corporations take on more influential roles.

PMID- 12800741
TI  - Compensation monitor. Liability insurance premium hikes take bite out of
      physicians' income.

PMID- 12800742
TI  - Is 1 the answer? More calling for single-payer system.

PMID- 12800743
TI  - Why looking for victims of domestic violence makes sense.

PMID- 12800744
TI  - Working together on the medical side.

PMID- 12800745
TI  - Employer coalition leaps at challenge of grappling with misaligned incentives.
      Interview by Patrick Muller.

PMID- 12800746
TI  - Shared appointments improve efficiency in the clinic.

PMID- 12800747
TI  - Rising costs strike unions as being cause for unrest.

PMID- 12800749
TI  - Keep politics out of examining room.

PMID- 12800748
TI  - A health care management company's experience with palivizumab--1 year later.

PMID- 12800750
TI  - Managed care outlook. Premiums up, benefits down for M+C.

PMID- 12800751
TI  - Dentistry and ayurveda--1.

PMID- 12800752
TI  - Proximate determinants of demand for oral health care in the surveyed households
      of Dharwad city, Karnataka India.
AB  - The study was undertaken to identify the factors influential in determining the
      demand for oral health care in the surveyed households of Dharwad city. Karnataka
      during May-July 2001. Dharwad city was divided into nine divisions in 1991
      census, in which four divisions were selected at random. A sample of 70
      households was selected randomly from each division. A total of 1381 persons from
      280 households only 208 persons were reported with various oral health problems
      during reference period of study. A significant positive relationship was
      observed between oral health care expenditure with the total number of visits (r
      = 0.4160, P < 0.01), the education of the sick person (r = 0.1983, p < 0.05), and
      the highest level of education among females (r = 0.1475, P < 0.05) and a
      significant negative relationship was observed between time gap between onset of
      disease and contact of health care centre (r = -0.1449, P < 0.05) and family size
      (r = -0.1518, P < 0.05) with expenditure. Path analysis results showed that, the
      duration of illness episode, the total number of visits to source of care during
      the reference period and distance between health care from the residence of the
      households (in km) are important variables in explaining increased oral health
      care expenditure.

PMID- 12800753
TI  - Liver ultrasound and faecal copper estimation in oral submucous fibrosis.
AB  - There is no evidence of an increased quantity of ingestion of copper in areca nut
      chewers by way of habitually swallowing the 'quid juice' allegedly contain
      'appreciable quantity' of soluble copper. Our experimental findings are favour of
      assuming that the amount of copper ingested, if at all, is well within the
      threshold limit of tolerance and therefore of no clinical significance. In
      conjunction with our earlier observation this study again proved the absence of
      visible and clinically/diagnostically detectable fibrosis in visceral organs,
      that includes liver, in patients suffering from advanced oral submucous fibrosis.

PMID- 12800754
TI  - Clear cell variant of mucoepidermoid carcinoma. Report of a case and a review of
      clear cell lesions of the oral cavity.

PMID- 12800755
TI  - Dental caries prevalence and experience among the group of institutionalized
      hearing impaired individuals in Pondicherry--a descriptive study.
AB  - A descriptive study was conducted among a group of hearing-impaired individuals
      in Pondicherry to assess the dental caries prevalence and experience. A total 114
      individuals were examined. The data was collected by direct clinical examination
      using appropriate indices and findings were recorded on the proforma sheets. The
      data were statistically processed and the results were obtained. Prevalence of
      dental caries in terms of DMFT is 42.98% and dft is 45%. Mean dft +/- s.d is 1.2
      +/- 1.38 and Mean DMFT +/- s.d is 1.0 +/- 1.42. It was concluded that in both
      permanent and deciduous dentition and the females have high caries prevalence.

PMID- 12800756
TI  - Association of parental consanguinity prevalent among those patients having
      dental anomalies. A retrospective study of 42 cases.

PMID- 12800757
TI  - A study on Candida carriage and cytological evaluation of oral mucosa in human
      immunodeficiency virus (HIV) patients.
AB  - This study was undertaken for identification and prevalence of various oral
      manifestations seen in the oral cavity of HIV infected patients. A quantitative
      evaluation of candida was done by counting the colony forming units from the oral
      cavity of HIV infected and non infected individuals. Further, cytopathological
      changes were evaluated in the oral mucosa of HIV infected patients. Study group
      consisted of 30 enzyme linked immunosorbent assay (ELISA) confirmed HIV
      seropositive patients, while the control group consisted of 10 subjects who were
      HIV negative (by ELISA).

PMID- 12800758
TI  - Assessment of chair side techniques for composite resin restoration--a survey.
AB  - The purpose of this survey was to assess the awareness of dental practitioners
      relating to chair side techniques in restoring teeth with light cure composite.
      The survey package consisted of a consent form, a leaflet stating the rationale
      and purpose of the survey and the questionnaire. Randomised sample of dental
      surgeons in practice was selected. The collected data was then analysed. A 52%
      response was obtained. Gross deficiencies in practice technique were observed,
      especially related to parameters like isolation, etching, bond and composite
      application and finishing of the restoration. Significantly individual assessment
      of problems by dental practitioners was found to be different from objective
      rationale. It is suggested that adequate and periodic re-evaluation of techniques
      must be made by the general dental practitioners, through continuing dental
      education or workshops so as to achiEve optimum quality.

PMID- 12800759
TI  - The direction and location of mental foramen and incidence of accessory mental
      foramen in south Indian mandibles.
AB  - One hundred and forty two south Indian mandibles of unknown sex were examined for
      the variations of the location and direction of the mental foramen. Accessory
      mental foramen were also looked for. The findings have been compared with those
      of other studies in the literature. Topography of the mental foramen is of
      practical importance to the dental and maxillo-facial surgeon for purpose of
      anesthesia and surgical procedures.

PMID- 12800760
TI  - Juvenile aggressive cemento-ossifying fibroma. A case report.
AB  - Juvenile Aggressive Cemento-Ossifying Fibroma is a benign, fibro osseous neoplasm
      commonly affecting maxilla but also other bones including mandible, arising in
      children. It is considered to be a locally aggressive and quickly expansile
      lesion. Because of its aggressive nature and high recurrence rate, an early
      detection and a complete surgical excision is essential. A case of Juvenile
      Aggressive Cemento-Ossifying Fibroma in a 9 year old male child who visited the
      Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital,
      Mysore is being reported and discussed.

PMID- 12800761
TI  - Peripheral myxoma of maxilla. A case report.
AB  - The intra-oral soft tissue myxoma or peripheral myxoma is a rare, slowly growing,
      benign mesenchymal tumor. Pathologically, it may be difficult to differentiate
      from other tumors with myoxid stroma and is occasionally misinterpreted as
      malignant. Though its counterpart, central odontogenic myxoma shows aggressive
      local behaviour and high recurrence rate following conservative excision, no much
      detail is available regarding peripheral myxoma of the oral cavity in the
      published English literature. In this paper, a rare case of peripheral myxoma of
      maxilla in a 35 years old female is presented with emphasis on review of relevant
      literature, histological aspects in differential diagnosis and 'semi-radical
      approach' in its management.

PMID- 12800762
TI  - Critical care advanced nursing practice.

PMID- 12800763
TI  - Critical care clinical nurse specialist.

PMID- 12800764
TI  - Critical care nurse practitioner.

PMID- 12800766
TI  - How will certification in critical care be of benefit to an organization?

PMID- 12800767
TI  - Intra-abdominal pressure monitoring for critically ill patients.
AB  - Increased intra-abdominal pressure (IAP) is associated with a variety of clinical
      situations and has profound effects, both locally and systemically, that may
      result in organ dysfunction and failure. If not identified and treated promptly,
      increased IAP can be fatal. Urinary bladder pressure monitoring is a simple and
      reliable method of quantifying IAP and is a key factor leading to prompt
      management and a successful outcome for patients.

PMID- 12800768
TI  - [Bacteria of the Burkholderia cepacia complex: specific features of diagnostics,
      genome organization and metabolism].
AB  - Modern data, related with the identification and typing of the complex B. cepacia
      bacteria, are analyzed in the article by using the poly-phase taxonomic approach.
      An optimal scheme for identifying and typing the complex B. cepacia bacteria,
      involving the microbiological and molecular-biological methods of laboratory
      diagnostics, is presented. The key and assumed factors of pathogenicity of the
      discussed bacteria are described. The possible phylogenetic relations of the
      complex B. cepacia bacteria with phytopathgens as well as with pathogenic
      bacteria of species Burkholderia, Pseudomonas, Escherichia, B. mallei, B.
      pdeudomallei, P. seruginosa and E. coli are described. A possible role of genome
      alterations and mutations in the genome of the complex B. cepacia bacteria (with
      the latter genome having unusual properties, i.e. a big size, and a considerable
      quantity of insertion sequences) in creating the conditions for the "pulsing"
      evolution "jerks", i.e. for a rapid change-over from saprophytism in the soil to
      a pathogenic causative agent of a viral-and-bacteriological infection. Such
      mechanism can be regarded as a rapid and radical adaptation of a microorganism
      under the conditions of changing ecological niches.

PMID- 12800769
TI  - [Correlation between activity of the phosphoenol-pyruvate-dependable
      phosphotransferase system (PTS) and synthesis of adhesion P1 protein in
      Mycoplasma pneumoniae].
AB  - Three isogenous strains M. pneumoniae, i.e. virulent FH, avirulent FH400 and a
      revertant with a restored virulence (FHR) and isolated from an avirulent strain,
      were studied. The mechanism of hemadsorption and the ability to cause an
      infection in Syrian hamsters were found to be damaged in the avirulent strain.
      The detection of a specific mRNA by the RT-PCR method showed, apart from the loss
      of the main adhesin (protein P1), a lack of general components of the phosphoenol
      pyruvat-dependable phosphotranspherase system (PTS), i.e. enzyme 1 and protein
      HPr. The recovery of virulence by passing an attenuated strain through animals
      with induced immunodeficiency correlated with the recovery of the activity of a
      gene encoding the P1 adhesion protein and with the onset of the PTS function
      activity. An analysis of published data was made use of to try to detect a
      correlation between the functional PTS activity in cell and virulence of M.
      pneumoniae.

PMID- 12800770
TI  - [Gene-engineering approach for the production of A and B toxin fragments for
      diagnostic and immunotherapeutic use in Clostridium difficile infection].
AB  - Clostridium difficle is a causative agent of severe and difficult-to-diagnose
      human infections. Toxins A and B, which modify the RAS-like proteins of
      eukaryotic cells, are the major factor in the pathogenicity of the discussed
      causative agent. These very toxins are considered as the key components of the
      developed diagnostic and therapeutic-and-preventive preparations. The C-terminal
      fragments of toxins A and B as well as hybrid products, consisting of fragments
      of both toxins, were cloned, within the present case study, by using the pET28
      plasmid vector. The recombinant plasmids were transformed into strains
      Escherichia Coli BL21 (DE3), and they were used later to produce the appropriate
      proteins. The purified protein preparations were isolated from the ultrasound
      bacterial-cell lysate by using the method of metal-affinity chromatography to be
      used later in the production of hyper-immune rabbit sera.

PMID- 12800771
TI  - [Effects of plasmid pKM101 on the expression of Escherichia coli and Salmonella
      typhimurium genes under ultraviolet irradiation].
AB  - The study focused on plasmid pKM101, which is a necessary component of the short
      term test of Eim's system (Salmonella-microsome test), to detect the potential
      carcinogens through their mutagen activity. We found a previously unknown feature
      of the plasmid to enhance the expression of certain plasmid and chromosome genes.
      The purpose of the present study was to examine and specify the role of operon
      mucAB responsible for the mutation properties of the plasmid in activating the
      expression of bacterial genes. An ultraviolet-induction examination of bacterial
      genes, with the mutants of plasmid pKM101 affecting operon mucAB being used,
      showed that the function of genes mucAB did activate, but, on the contrary,
      suppressed the induction of genes elt (i.e. of genes controlling the formation of
      LT-toxin of Escherichia coli) and of sfiA (SOS-regulated gen E. col controlling
      the cell division.

PMID- 12800772
TI  - [Multilocus sequence-typing for characterization of Moscow strains of Haemophilus
      influenzae type b].
AB  - Haemophilius influenzae, type b (Hib) bacteria, were genotyped by multilocus
      sequence typing (MLST) using 5 loci (adk, fucK, mdh, pgi, recA). 42 Moscow Hib
      strains (including 38 isolates form cerebrospinal fluid of children, who had
      purulent meningitis in 1999-2001, and 4 strains isolated from healthy carriers of
      Hib), as well as 2 strains from Yekaterinburg were studied. In MLST a strain is
      characterized, by alleles and their combinations (an allele profile) referred to
      also as sequence-type (ST). 9 Sts were identified within the Russian Hib
      bacteria: ST-1 was found in 25 strains (57%), ST-12 was found in 8 strains (18%),
      ST-11 was found in 4 strains (9%) and ST-15 was found in 2 strains (4.5%); all
      other STs strains (13, 14, 16, 17, 51) were found in isolated cases (2.3%). A
      comparison of allelic profiles and of nucleotide sequences showed that 93% of
      Russian isolates, i.e. strain with ST-1, 11, 12, 13, 15 and 17, belong to one and
      the same clonal complex. 2 isolates from Norway and Sweden from among 7 foreign
      Hib strains studied up to now can be described as belonging to the same clonal
      complex; 5 Hib strains were different from the Russian ones.

PMID- 12800773
TI  - [Use of PCR and nucleotide sequence analysis of the VP7 gene for detection of
      bovine rotaviruses and identification of their G serotypes].
AB  - A Vp7 gene fragment PCR protocol was developed to detect the bovine rotaviruses
      and to identify their G serotypes. The most widespread bovine rotaviruses of G
      serotypes (G6, G8 and G10) can be distinguished on the basis of the PCR fragment
      size, while other G serotypes can be differentiated through a comparative
      analysis of the VP7 gene fragment nuclcotide sequence. Twenty-four bovine
      rotavirus field isolates were detected, and their G stereotypes were determined
      by using the method in question. Fourteen isolates were shown to be of G6
      serotype; four of them were of G8, five--of G10, and one isolate was of G11
      serotype. A possibility of detecting more than one isolate by this method was
      shown. Finally, a feasibility of using the method for searching for rotaviruses
      of new bovine rotavirus G serotypes and for rotaviruses, which do not belong to a
      so far described G serotypes, is discussed.

PMID- 12800774
TI  - [Development of a PCR-based method for diagnostics of mycoses].
AB  - Since the express-diagnostics of mycoses in immune-deficit patients still remains
      an acute problem, we developed an effective test system (Kan-Am) to detect DNA
      Candida albicans, which is a leader in the list of causative agents of
      candidosis. A comparison study of three PCR-systems used to detect a broad
      spectrum of fungoid pathogens was carried out, and a universal system (FungAm),
      which ensures the detection of DNAs of above 78 strains of 25 types of pathogenic
      fungi, was selected. The results of clinical testing of the species-specific and
      universal PCR-systems are well confirmed by the culture method, and they are
      indicative of the efficacy of applying them for the diagnostics of mycoses in
      neonatology. The use of the mentioned systems is a promising factor for the
      express-diagnostics of mycoses in immunodeficiency patients. The high sensitivity
      of the method makes it possible to detect 10 to 100 cells of a causative agent in
      100 mcl of the examined biological material, which is compatible with the culture
      method. A kit of dry reagents (IonoMix) designed for an accelerated sample
      preparation and isolation, from them, of DNAs on the basis of Chelex-100 and of
      proteinase K was worked out; the kit is portable and meant for a long-term
      storing.

PMID- 12800776
TI  - Sleep-related breathing disorders: new developments. Preface.

PMID- 12800775
TI  - [Analysis of antigenic determinant profiles of the Ebola virus VP35 protein N
      terminal region using its short recombinant fragments].
AB  - cDNA of fragments of gene VP35 of the Ebola virus (EV) were expressed in vector
      pQE30 for the purpose of isolation of recombinant fragments of protein VP35. Five
      short affinity-purified fragments of the EV VP35 protein were analyzed, by using
      the methods of IEA and immunoblotting, with polyclonal antiviral sera (PAS)
      against EV and with hybrid monoclonal antibodies (Mabs) IC6 and 6F7 specific to
      EV VP35 protein. All fragments of protein VP35 with an intact N-terminal region
      and removed C-terminal region were found to interact effectively with PAS and
      with Mabs IC6 and 6F7. Rec86N, the smallest of the above fragments, comprised the
      initial 86 amino acid residues of the VP35 N-terminal region. A removal of 36
      amino acid residues from the N-terminal region of Rec310N, the largest
      recombinant fragment, resulted in a loss of interaction with Mabs IC6 and 6F7,
      while the interaction with polyclonal antibodies remained intact. The obtained
      results show that the initial 86 amino acid residues of the N-terminal region of
      EV VP35 are of the key importance in forming the antigenic structure of VP35 and
      that they contain multiple B-cell epitopes. Finally, the initial 36 amino acids
      of VP35 predetermine the shaping-up of two antigenic determinants for Mabs IC6
      and 6F7.

PMID- 12800777
TI  - Molecular and physiologic basis of obstructive sleep apnea.
AB  - Obstructive sleep apnea-hypopnea syndrome occurs because of various combinations
      of anatomic, mechanical, and neurologic anomalies that jeopardize ventilation
      only when normal state-dependent reductions in drive to upper airway respiratory
      muscles and pump muscles occur. A well thought out and carefully described
      infrastructure of the normal and abnormal physiology in persons with OSAHS has
      been developed over the past few decades, which enables the development of
      innovative and largely effective therapies. The most recent data complement the
      infrastructure with the neurochemical changes underlying the state-dependent
      respiratory disorder and observations that the disease process itself can impair
      muscles, neural inputs, and soft tissue in a manner that has the potential to
      worsen disease. Oxidative and nitrosative stress from the repeated oxyhemoglobin
      desaturations and re-oxygenations is implicated in the injury to these tissues.
      An improved understanding of the mechanisms through which OSAHS progresses may
      lead to alternative therapies and aid in the identification of persons at risk
      for disease progression.

PMID- 12800778
TI  - Cardiovascular consequences of obstructive sleep apnea.
AB  - Sleep apnea is associated with several cardiovascular disease conditions. A
      causal relationship between sleep apnea and each of these diseases is likely, but
      remains to be proven. The clearest evidence implicating OSA in the development of
      new cardiovascular disease involves data that show an increased prevalence of new
      hypertension in patients with OSA followed over 4 years [3]. Circumstantial
      evidence and data from small study samples suggest that OSA, in the setting of
      existing cardiovascular disease, may exacerbate symptoms and accelerate disease
      progression. The diagnosis of OSA always should be considered in patients with
      refractory heart failure, resistant hypertension, nocturnal cardiac ischemia, and
      nocturnal arrhythmias, especially in individuals with risk factors for sleep
      apnea (e.g., central obesity, age, and male gender). Treating sleep apnea may
      help to achieve better clinical control in these diseases and may improve long
      term cardiovascular prognosis.

PMID- 12800779
TI  - Heart failure and sleep apnea: emphasis on practical therapeutic options.
AB  - Heart failure is a highly prevalent problem associated with excess morbidity and
      mortality and economic impact. Because of increased average life span, improved
      therapy of ischemic coronary artery disease and hypertension, the incidence and
      prevalence of heart failure will continue to rise into the twenty-first century.
      Multiple factors may contribute to the progressively declining course of heart
      failure. One such cause could be the occurrence of repetitive episodes of apnea,
      hypopnea, and hyperpnea, which frequently occur in patients with heart failure.
      Episodes of apnea, hypopnea, and hyperpnea cause sleep disruption, arousals,
      intermittent hypoxemia, hypercapnia, hypocapnia, and changes in intrathoracic
      pressure. These pathophysiologic consequences of sleep-related breathing
      disorders have deleterious effects on cardiovascular system, and the effects may
      be most pronounced in the setting of established heart failure and coronary
      artery disease. Diagnosis and treatment of sleep-related breathing disorders may
      improve morbidity and mortality of patients with heart failure [34]. Large-scale,
      carefully executed therapeutic studies are needed to determine if treatment of
      sleep-related breathing disorders changes the natural history of left ventricular
      failure.

PMID- 12800780
TI  - Sleep-disordered breathing and stroke.
AB  - Sleep-related breathing disorders are strongly associated with increased risk of
      stroke independent of known risk factors. The direction of causation favors sleep
      disordered breathing leading to stroke rather than the other way around, although
      definitive proof of this awaits the results of prospective cohort studies. If
      causal, even a moderately elevated risk of stroke coupled with the high
      prevalence of sleep-disordered breathing could have significant public health
      implications. The relationship between sleep-disordered breathing and stroke risk
      factors is complex, and likely part of the risk for cerebrovascular events is
      because of higher cardiovascular risk factors in patients with increased RDI. The
      mechanisms underlying this increased risk of stroke are multi-factorial and
      include reduction in cerebral blood flow, altered cerebral autoregulation,
      impaired endothelial function, accelerated atherogenesis, thrombosis, and
      paradoxic embolism. Because of the effects of sleep-disordered breathing on
      vascular tone, hypertension is believed to be a major mechanism by which sleep
      disordered breathing might influence risk of stroke. Because sleep-related
      breathing disorders are treatable patients with stroke/TIA should undergo
      investigation, with a thorough sleep history interview, physical examination, and
      polysomnography. Treatment of sleep apnea has been shown to improve quality of
      life, lower blood pressure, improve sleep quality, improve neurocognitive
      functioning, and decrease symptoms of excessive daytime sleepiness [98]. Further
      treatment trials are needed to determine whether treatment improves outcome after
      stroke and whether treatment may serve as secondary prophylaxis and modify the
      risk of recurrent stroke or death.

PMID- 12800781
TI  - Obstructive sleep apnea in epilepsy.
AB  - Obstructive sleep apnea can affect an individual with epilepsy profoundly. These
      relatively common disorders can coexist and potentially exacerbate each other.
      The identification and appropriate treatment of OSA may have far-reaching
      consequences in improving a patient's quality of life and recurrence of seizures.
      Clinicians must be aware of the relationship of these disorders and keenly
      question epilepsy patients, regardless of their body habitus, regarding potential
      symptoms of sleep apnea. Although the underlying pathogenic mechanisms are
      unclear, we can model the information gained from the observations to further the
      understanding of the relationship between sleep and epilepsy.

PMID- 12800782
TI  - Neuropsychological impairment and quality of life in obstructive sleep apnea.
AB  - Although clinical experience has suggested for more than two decades that OSA is
      associated with impairment of cognition, emotional state, and quality of life and
      that treatment with nasal CPAP produces significant improvements in these areas,
      sound empirical evidence to support this view, especially regarding treatment
      outcome, has been lacking. More recent investigations have begun to provide this
      support from randomized, adequately controlled studies. These assessments suggest
      that some degree of cognitive dysfunction is associated with OSA. The effects are
      most apparent in the severe cases, whereas results in mild cases are more
      equivocal. Reported impairments include global intellectual dysfunction and
      deficits in vigilance, alertness, concentration, short- and long-term memory, and
      executive and motor function. Considerable discrepancy exists across studies with
      respect to type and degree of dysfunction, however. Disturbances in general
      intellectual function and executive function show strongest correlations with
      measures of hypoxemia. Not unexpectedly, alterations in vigilance, alertness,
      and, to some extent, memory seem to correlate more with measures of sleep
      disruption. Although many inadequately controlled investigations have
      demonstrated reversibility of most or all of these deficits with effective
      treatment, more recent placebo-controlled studies have raised doubts regarding
      whether the observed changes are truly a function of treatment. This issue
      requires further systematic exploration with adequate controls and step-wise
      analysis of treatment duration effects. A similar set of considerations exists
      with respect to the relationship between psychological disturbance, primarily
      depression, and OSA. Although several studies suggest significant depression in
      these patients, the results are mixed. Placebo-controlled treatment trials fail
      to demonstrate consistently a difference in mood improvement between active
      treatment groups and controls, although several methodologic considerations
      suggest that these results should be interpreted with caution. Numerous
      investigations leave little doubt about the issue of quality of life impairment
      among persons with OSA. Further characterization of impairment, particularly in
      areas specific to this population, will provide clearer understanding of the
      problem. Preliminary investigations of treatment response in controlled studies
      indicate significantly greater improvement of quality of life in response to
      CPAP. Although patients with OSA commonly report disturbances in cognitive and
      psychological function and general quality of life, the increased rates of
      obesity, hypertension, diabetes, cardiovascular disease, medication use, and
      related psychosocial complications present a host of potential etiologies that
      might explain the impairments noted. There can be little doubt that these
      covariants do, in some cases, contribute to neuropsychological dysfunctions. It
      is essential that future studies continue to define those disturbances that are
      specific to OSA, the relationship between levels of severity and impairment, the
      role of treatment in reversing these dysfunctions, and the correlation between
      test results and significant day-to-day social and occupational functional
      impairment.

PMID- 12800783
TI  - Obstructive sleep-disordered breathing in children: new controversies, new
      directions.
AB  - Although it may seem that confusion and uncertainty reign in the field of
      pediatric sleep medicine, the recent realizations that the scope of childhood SDB
      is wider, the symptomatology is broader, and the prevalence is higher than
      previously believed are major advances. Likewise, recent acknowledgment of the
      lack of true "gold standards" for diagnosing UARS and OSAS in children is also a
      major advancement in this field. Critical assessment of the current "state of the
      art" by the 2002 AAP Technical Report on the Diagnosis and Management of
      Childhood Obstructive Sleep Apnea Syndrome [37] is another major advance that
      sets the stage for the next steps. The field needs an evidence-based definitions
      conference, standardization of definitions across all research studies, and much
      more research on clinical features, pathophysiology, diagnosis, and treatment of
      the "new" obstructive SDB, including the full range of morbidity caused by
      increased upper airway resistance. This should include further inquiry into the
      origins of adult morbidity that resulted from childhood SDB and how it can be
      prevented.

PMID- 12800784
TI  - State of home sleep studies.
AB  - Many different portable monitors have been used to assess patients with suspected
      sleep apnea. There is limited evidence for the use of type 2 monitors, especially
      in the unattended setting in which there may be high rates of data loss. Type 3
      monitors have low likelihood ratios for negative tests and can be used to "rule
      out" sleep apnea. The ability of type 3 monitors to "rule in" sleep apnea is less
      convincing, but this may improve with the use of improved technology, such as
      nasal pressure transducers. Type 4 monitors usually use oximetry and can be used
      to "rule out" sleep apnea. Higher sampling rates and improved analysis algorithms
      can improve the specificity of these monitors; hence, likelihood ratios for a
      positive test result can be high enough with some monitors to "rule in" sleep
      apnea as well. Not all monitors record and analyze signals in the same way; it is
      not possible to generalize results from one monitor across all monitors of a
      particular type. Limited evidence is available for many portable monitors in the
      unattended setting, and further research is required in this area. Clinicians
      should identify how they plan to use a portable monitor: as a mechanism to
      exclude disease in asymptomatic snorers, to confirm disease in [figure: see text]
      patients with a high clinical probability of disease, or to risk stratify
      patients so that proper priority for polysomnography can be determined. This
      determination allows them to select a portable monitor with signals most
      appropriate to their needs. The quality of the validation studies for each
      portable monitor also should be evaluated carefully before implementation in
      clinical practice. The ability for a clinician to review raw data manually and
      consider artifact is a necessary feature. Measurement of oxygen saturation also
      is important to identify patients with previously unsuspected serious
      desaturation that would indicate the need for more urgent treatment. In centers
      in which polysomnography is not readily available, a clinical decision algorithm
      that incorporates a clinical prediction rule with the use of portable monitors
      can guide clinicians toward institution of therapy or further investigations.
      Intuitively, this approach could reduce waiting times for polysomnography and
      delays in diagnosis, but additional evidence for the validity and cost
      effectiveness of this approach is required.

PMID- 12800785
TI  - Monitoring respiration during sleep.
AB  - The sleep-related breathing disorders have been categorized in various ways. The
      most basic schema divides them into obstructive or central apneic events. An
      American Academy of Sleep Medicine (AASM) Task Force Report published in 1999
      defined four separate syndromes associated with abnormal respiratory events
      during sleep among adults, namely, obstructive sleep apnea-hypopnea syndrome
      (OSAHS), central sleep apnea-hypopnea syndrome, Cheyne-Stokes breathing syndrome,
      and sleep hypoventilation syndrome. In this classification, the upper airway
      resistance syndrome was not regarded as a distinct syndrome; instead, respiratory
      event-related arousals (RERAs) were considered part of the syndrome of OSAHS.

PMID- 12800786
TI  - Indications for treatment of obstructive sleep apnea in adults.
AB  - Obstructive sleep apnea is associated with significant daytime sleepiness,
      reduced quality of life, insulin resistance, motor vehicle crashes, vascular
      morbidity and mortality. Current evidence supports the belief that all these
      parameters can be impacted favorably by treatment. Medical therapy with positive
      pressure eliminates snoring and favorably affects daytime sleepiness, driving
      risk, vascular function, vascular risk, and quality of life. Treatment may be
      difficult to accept or adhere to, and some treatment options are not uniformly
      effective. The long-term impact of treatment is uncertain.

PMID- 12800787
TI  - Continuous positive airway pressure: new generations.
AB  - Automatic positive airway pressure devices are the most technologically advanced
      positive airway pressure devices available for use in OSA. Although
      heterogeneous, they have in common the ability to detect and respond to changes
      in upper airway resistance. Data cannot necessarily be extrapolated from one
      device to another, and the field is rapidly advancing. Most studies of APAP have
      been performed in a supervised setting, or patients have been carefully selected
      to have a high likelihood of OSA uncomplicated by disorders such as alveolar
      hypoventilation or central apnea or technical problems such as mask leaks.
      Studies of APAP for the diagnosis of OSA have shown that APAP can diagnose severe
      OSA effectively, but the diagnosis of mild-moderate OSA is less reliable. APAP
      devices also can be effective therapy for selected patients with OSA, with
      overall similar results to conventional fixed CPAP in terms of respiratory
      disturbances, sleep quality, nocturnal oxygenation, and daytime sleepiness and
      performance, with less known or other long-term outcomes. In most studies, mean
      treatment pressures are lower, without change in side effect profile. Compliance
      and preference with APAP are similar to or somewhat better than CPAP in most
      studies. APAP also can be used in an attended setting to titrate an effective
      pressure for use in long-term conventional CPAP therapy, also with similar
      results to CPAP in many patients. APAP devices are more expensive than CPAP
      devices, but the cost may be outweighed if a group of patients who can be
      diagnosed, treated, or titrated safely in the unattended setting can be
      identified. Although diagnostic and therapeutic algorithms for APAP have been
      proposed, the best candidates for this modality must be defined better.

PMID- 12800788
TI  - Behavioral and pharmacologic therapy of obstructive sleep apnea.
AB  - Previous attempts at using pharmacologic agents in the treatment of OSA have been
      disappointing. Medroxyprogesterone has not been found to be useful in the
      treatment of OSA. Use of protriptyline is limited by frequent side effects, but
      its role in mild and REM-related OSA must be clarified. SSRIs seem to be
      ineffective in treatment of severe OSA. Further studies are needed to determine
      their effect in persons with mild disease. This is important because patients
      with mild OSA (AHI < 15 hours) are most likely to be noncompliant with CPAP
      therapy [91]. A recent systematic review of drug treatments for OSA concluded
      that the current data do not support the use of any drug as an alternative to
      CPAP [92]. Of 56 studies identified, only 9 studies met methodologic criteria.
      Clearly, basic research and adequately powered clinical trials are needed to
      identify an effective medication for OSA.

PMID- 12800789
TI  - The role of oral appliance therapy in the treatment of obstructive sleep apnea.
AB  - The development of oral appliance treatment for OSA represents an important step
      in the management of this disease. Randomized, controlled clinical trials have
      shown them to be an effective treatment option for snoring and OSA in some
      patients, particularly patients with less severe OSA or simple snoring and
      patients who have failed other treatment modalities. Although oral appliances are
      not as effective as CPAP therapy, they work in most patients to relieve symptoms
      and apnea and are well tolerated by patients. Most patients report improvements
      in sleep quality and excessive daytime sleepiness. Short-term side effects are
      generally minor and are related to excessive salivation, jaw and tooth
      discomfort, and occasional joint discomfort. These symptoms may lead to
      discontinuation of appliance therapy but usually improve in most patients over
      time. Serious complications are not common, but occlusal changes are more common
      than previously believed.

PMID- 12800790
TI  - Surgical management of obstructive sleep apnea.
AB  - Nasal CPAP is and should be the first-line treatment for OSA. Any physician who
      uses nasal CPAP undoubtedly recognizes that this treatment modality has
      limitations, however. The authors believe that surgery offers a viable
      alternative to nasal CPAP in patients who are intolerant of nasal CPAP. Potential
      risks and complications must be explained fully to any potential surgical
      candidate. The selection of surgical procedure(s) should be determined based on a
      patient's airway anatomy, medical status, severity of sleep apnea, and his or her
      desire and preference.

PMID- 12800791
TI  - A 42-year-old woman with breast cancer.
AB  - This premenopausal women has a T1c, N1 (two nodes positive) ER-positive, PR
      weakly positive, HER2 FISH-positive, grade 3 invasive ductal carcinoma. She has
      been treated with lumpectomy and axillary node dissection. The recommendation of
      the panel is for her to join one of the randomized trials studying the role of
      trastuzumab in node-positive breast cancers. Off protocol, we would recommend
      adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by docetaxel,
      although numerous options are available. Chemotherapy would be followed by
      radiation therapy and hormonal treatment. At this point, we recommend tamoxifen,
      with consideration to adding goserelin (Zoladex) if the patient does not remain
      amenorrheic. The patient chose to enter the Intergroup trastuzumab trial.

PMID- 12800792
TI  - Hematopoietic stem cell transplantation for non-Hodgkin's lymphoma.
AB  - High-dose myeloablative therapy with autologous or allogeneic stem cell rescue is
      an effective treatment strategy for non-Hodgkin's lymphoma (NHL), but NHL is much
      less likely to stay in remission after an autologous transplant than after an
      allogeneic transplant. The benefit of undergoing an autologous transplant earlier
      in the course of the disease, especially for patients who present with
      intermediate or high scores on the International Prognostic Index of risk
      factors, is still unclear. The addition of immunotherapy, biologic modifiers, and
      antibody therapy such as rituximab (Rituxan) or radiolabeled antibody to the
      autologous transplant are approaches undergoing evaluation. Historically, there
      has been a high regimen-related mortality rate associated with myeloablative
      allogeneic transplant that has made this approach a less appealing option for
      therapy. The use of nonmyeloablative allogeneic transplants as treatment for NHL
      is less well studied and remains to be defined.

PMID- 12800793
TI  - Long-term toxicities of selective estrogen-receptor modulators and antiaromatase
      agents.
AB  - Published literature indicates that the selective estrogen-receptor modulators
      (SERMs) tamoxifen and raloxifene (Evista) have favorable effects on bone density,
      lipid profiles, and the incidence of second breast cancers, and unfavorable
      effects on the incidence of venous thrombosis and hot flushes. Tamoxifen
      increases the risk of endometrial cancer, but raloxifene does not. The effects of
      SERMs on sexual function and cognition are unclear. Because the selective
      antiaromatase agents are relatively new, the long-term effects of these agents on
      normal tissues are less well established. It appears that the nonsteroidal agents
      (anastrozole [Arimidex], letrozole [Femara]) and steroidal (exemestane
      [Aromasin]) antiaromatase agents may have different effects on normal tissues.
      Preliminary data demonstrate that anastrozole increases the risk of arthralgias
      and produces a decrease in bone density. In contrast, exemestane appears to
      favorably affect bone density and lipid profile, similar to tamoxifen and
      raloxifene. The incidence of contralateral breast cancer is decreased in women on
      adjuvant anastrozole, but data for the other antiaromatase agents are not yet
      available. Hot flushes have been reported with the use of selective aromatase
      inhibitors, but their incidence seems to be comparable to what is reported with
      SERMs. Antiaromatase agents do not appear to cause venous thrombosis. More
      information about the effects of the antiaromatase agents on normal tissue will
      become available as data from ongoing adjuvant and chemoprevention trials are
      reported. Clinically, we should be conscious of the differences between
      antiaromatase agents and SERMs and their impact on women's health.

PMID- 12800794
TI  - Clinical trials referral resource. Current clinical trials of bortezomib.

PMID- 12800795
TI  - The evolving role of cytoreductive surgery for metastatic renal cell carcinoma.
AB  - Metastatic renal cell carcinoma is a devastating disease associated with poor
      survival. Immunotherapy is the mainstay of treatment, but response rates are low.
      The role of cytoreductive surgery in the presence of metastatic disease is
      evolving. From both retrospective and recently published randomized clinical
      trials, it is now apparent that among patients with metastatic renal cell
      carcinoma and good performance status, cytoreductive surgery followed by
      immunotherapy improves survival. However, this approach is likely to be
      detrimental in patients with poor performance status. Clinical trials of novel
      agents remain a priority in this disease.

PMID- 12800796
TI  - Adjuvant therapy in gastric cancer: can we prevent recurrences?
AB  - Despite a dramatic decline in the incidence of gastric carcinoma in the United
      States during the past century, treatment remains a challenging problem for
      oncologists. Surgery continues to be the primary modality for managing early
      stage gastric cancer, but up to 80% of patients who undergo a "curative"
      resection develop locoregional or distant recurrence. Given these sobering
      statistics, there has been great interest in developing strategies to prevent
      recurrences after surgery and improve overall mortality. In this article, we
      review data on adjuvant treatment modalities for this disease, including
      radiotherapy, chemotherapy, combination chemotherapy and radiation,
      intraperitoneal treatment, and immunotherapy. We focus attention on the recent
      widespread acceptance of adjuvant chemoradiotherapy, based on the results of
      Intergroup trial 0116. Future strategies incorporating different modalities of
      treatment will be outlined.

PMID- 12800797
TI  - First clinically useful marker for lung cancer identified.

PMID- 12800798
TI  - Management of hyperbilirubinemia in the healthy term newborn.

PMID- 12800799
TI  - Motivating health: strategies for the nurse practitioner.
AB  - PURPOSE: To provide the nurse practitioner (NP) with a practical prescription for
      acquiring expertise in health behavior change using integrated principles from
      the transtheoretical model of change and motivational interviewing. DATA SOURCES:
      Extensive literature review of current theory and research on health behavior
      change. CONCLUSION: Expertise in motivating health behavior change is essential
      to effective health promotion and to the NP role. IMPLICATIONS FOR PRACTICE:
      Lifestyle choices are principal contributors to the leading causes of death and
      most chronic diseases in the United States. Traditional health behavior
      interventions are often ineffective in motivating and sustaining lifestyle
      change.

PMID- 12800800
TI  - Diabetes medical nutrition therapy: practical tips to improve outcomes.
AB  - PURPOSE: To describe the evolving and expanding role of nurse practitioners (NPs)
      in providing diabetes medical nutrition therapy (MNT) as the United States faces
      epidemics of diabetes and obesity. DATA SOURCES: Scientific literature and
      reports from the public health, diabetes, and nutrition fields. CONCLUSIONS:
      Although clinically effective for both prevention and treatment of diabetes, MNT
      is often underutilized. The majority of people with diabetes are cared for by
      primary care providers; the role of NPs as primary care providers is evolving and
      expanding. NPs are recognized as leaders who creatively adapt to the rapidly
      changing health care delivery system. IMPLICATIONS FOR PRACTICE: NPs can serve as
      role models by presenting accurate, basic nutrition messages, referring patients
      to registered dietitians for MNT, reinforcing nutrition and the importance of
      lifestyle change as primary treatments for their disease, and following up on
      their patients' progress with nutrition interventions.

PMID- 12800801
TI  - Health problems of women with severe mental illness.
AB  - PURPOSE: To provide a review of the health problems of women with severe mental
      illness (SMI) that are related to their psychiatric disorders and disabilities,
      prolonged use of psychotropic medications, and high-risk lifestyle practices.
      DATA SOURCES: Review of current literature uncovered through MEDLINE, Cumulated
      Index to Nursing and Allied Health, and Psychological Abstracts as well as the
      authors' clinical experiences. CONCLUSIONS: Women with SMI are at increased risk
      for obesity as well as cardiovascular, endocrine, and infectious disorders. They
      also experience psychotropic medication-related disorders such as amenorrhea,
      galactorrhea, sexual dysfunction, breast cancer, and osteoporosis. High-risk
      lifestyle practices, excessive weight gain, low physical activity, substance
      abuse and unprotected sexual activity increase risk for health problems. The
      mental illness, residual disabilities, sequelae of childhood abuse, poverty,
      limited social support and health knowledge deficits affect their ability to
      maintain optimum health. IMPLICATIONS FOR PRACTICE: Knowledge about women with
      SMI and their health problems will enable nurse practitioners to better meet the
      needs of this vulnerable population.

PMID- 12800802
TI  - Case study of a young man with tremor.
AB  - PURPOSE: To provide the clinician with an opportunity to review the most common
      causes of tremor in young adults. DATA SOURCES: Extensive review of international
      scientific literature on tremors and other movement disorders, supplemented by a
      recent case study. CONCLUSIONS: Essential tremor (ET) is the most common tremor
      disorder in the world. In contrast to common expectations, the 2nd decade of life
      represents a period of peak incidence. The early presentation may be so mild that
      the tremor goes unnoticed by patients and clinicians for many years. The most
      important movement disorder to rule out in the workup of patients with tremors is
      Parkinson's disease. IMPLICATIONS FOR PRACTICE: The diagnosis of ET is generally
      made on clinical grounds. A comprehensive history and careful physical
      examination that rules out cerebellar or extrapyramidal disease is required. The
      clinician must distinguish between resting tremors and action tremors. If the
      appropriate diagnosis is unclear, a tremor recording (electromyogram) may assist
      in this distinction. Referral to a neurologist may be warranted.

PMID- 12800803
TI  - Nutritional health promotion for older adults, where is the content?
AB  - PURPOSE: To describe nurse practitioners' (NPs') educational experiences related
      to older adult nutrition and eating abilities. DATA SOURCES: Descriptive research
      with written survey data collected from 80 gerontological NPs recruited from a
      national nursing conference. CONCLUSIONS: Older adults' nutritional health has
      been related to acute illness, pressure sore development, prolonged hospital
      stays, and other health problems. Current literature suggests that although
      nutrition screening and intervention promote older adults' health, practitioners
      may not consistently receive education on this content. Participants indicated
      that gerontological-nutrition content was important, that it was missing from
      their educational programs, and that it needed to be a part of the NP curriculum.
      Specific nutrition content concerns were organized by the categories (a) disease
      and functional issues, (b) psychosocial support and environmental impact, and (c)
      health care team and system considerations. IMPLICATIONS FOR PRACTICE: NP
      programs need to self-evaluate for adequate and appropriate nutrition screening
      and intervention content. Frameworks such as those developed by the Nutrition
      Screening Initiative and others provide beginning guidance for further content
      development.

PMID- 12800804
TI  - Nurse practitioner coding practices in primary care: a retrospective chart
      review.
AB  - PURPOSE: To describe the coding and documentation practices of nurse
      practitioners (NPs) when using evaluation and management (E & M) codes in an
      academic primary care center. DATA SOURCES: A randomized retrospective review of
      ten charts from a nurse-managed primary care clinic affiliated with a midwestern
      research-intensive university. CONCLUSION: The findings demonstrate that the
      documentation in the chart for six of the ten client encounters did not support
      the E & M codes assigned by the clinicis NPs. Four of these six client encounters
      were overcoded; the remaining two encounters were undercoded. IMPLICATIONS FOR
      PRACTICE: Findings of this study support the need for additional education of NPs
      in the areas of coding and documentation.

PMID- 12800805
TI  - Endothelial binding of recombinant tissue plasminogen activator: quantification
      in vivo using a recirculatory model.
AB  - Binding of tissue plasminogen activator (t-PA) to the endothelium may be
      important in the prevention of thrombus formation. The aim was to develop a
      method to quantify endothelial binding in vivo. Nine healthy male volunteers
      received a 40 min continuous infusion with low dose recombinant t-PA (3.75
      micrograms/min) and an indocycanine green infusion (0.5 mg/min) as control. A
      three-compartment recirculatory model was developed to account for non-specific
      circulatory delay effects. t-PA antigen, activity and t-PA/PAI-1 complex profiles
      showed a marked delay in increase at the beginning of the infusion. A reversible
      and concentration-dependent binding component was incorporated in the model which
      resulted in an accurate description of the t-PA concentration profile. t-PA
      binding was characterized by a dissociation constant of 5.9 ng/ml (SEM 1.8, CV
      0%; fixed) and a binding capacity of 70 micrograms t-PA (SEM 10, CV 48%). This
      model can be used as a tool to quantify the ability of the endothelium to bind t
      PA.

PMID- 12800806
TI  - Competition between acetylcholine and a nondepolarizing muscle relaxant for
      binding to the postsynaptic receptors at the motor end plate: simulation of
      twitch strength and neuromuscular block.
AB  - The goal of the study was to simulate twitch strength and neuromuscular block
      produced by nondepolarizing muscle relaxants. METHODS: In the proposed model,
      affinities of the two binding sites at a single postsynaptic receptor for
      acetylcholine (A) and the muscle relaxant (D) define the formation of three
      complexes with A only, three complexes with D only, and two complexes with both A
      and D. Twitch strength was postulated to be a function of the receptors with both
      binding sites occupied by A, and two constants. Neuromuscular block (NMB) was
      calculated from NMB = 1-twitch. RESULTS: Stimulus-induced release of A results in
      rapid, but transient, changes in the concentrations of free A, the eight
      complexes, and the unoccupied receptors. Muscle relaxants that display either a
      congruous or an inverse pattern of affinities for the binding sites relative to
      those of A produce NMB vs. [D] curves with slightly different slopes but markedly
      different estimates for IC50. Depending on the number of activated receptors at
      the end plates of muscle fibers, the simulations represent the distributions of
      contracting fibers in a whole muscle. CONCLUSION: Simulations of competition
      between A and D for binding to two sites at a receptor reveal that the potencies
      of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves
      depend on (1) the affinities of D for the two binding sites, (2) the orientation
      of the affinities relative to those of A, and (3) the affinities of A for the
      same two sites.

PMID- 12800807
TI  - Estimation of population pharmacokinetic parameters in the presence of non
      compliance.
AB  - In population pharmacokinetic (PK) studies, patients' drug plasma profiles are
      routinely analyzed assuming that all patients took their drug at the times and in
      the amounts specified. However, patient non-compliance with the prescribed drug
      regimen is a leading source of failure to drug therapy. It has been reported that
      over 30% of patients routinely skip doses regardless of their disease, prognosis,
      or symptoms. This brings into question the assumption regarding full compliance
      for population PK analyses. This paper describes the estimation of population PK
      parameters in the presence and absence of non-compliance while either assuming
      full compliance or estimating compliance using a hierarchical Bayesian approach.
      Assessment of compliance for a given dose was limited to one of three
      possibilities: no dose was taken at the prescribed time, the prescribed dose was
      taken at the prescribed time, or twice the prescribed dose was taken at the
      prescribed time. Simulated data sets based on a one-compartment pharmacokinetic
      model with first order elimination were analyzed using WinBUGS (Bayesian
      inference Using Gibbs Sampling) software. An initial feasibility simulation
      experiment, using a simple, but informative PK sampling design with bolus input
      of drug, was performed. A second simulation study was then carried out using a
      more realistic sampling design and first-order input of drug. The simulated
      sampling design included observations after known doses as well as after
      uncertain doses. Results from the feasibility study revealed that when compliance
      was estimated instead of being assumed to be 100%, the relative prediction error
      for clearance (CL) decreased from 0.25 to 0.10 for 60% compliance and from 0.6 to
      0.2 for 35% compliance. Estimates of the interoccasion variability of clearance
      were improved by compliance estimation but still had substantial positive bias.
      Estimated of interindividual variability were relatively insensitive to
      compliance estimation. Estimates for volume of distribution (V) and its
      associated variances were not affected by incorporation of compliance estimates,
      perhaps due to the specific sampling design that was used. The design was
      relatively uninformative regarding V. In the more realistic study, estimates for
      CL, V and the difference between the absorption rate constant and the elimination
      rate constant (KA-K) were improved by the incorporation of compliance estimation.
      The median relative errors were reduced from 0.51 to -0.01 for CL, from 0.49 to
      0.04 for V, and from 0.49 to -0.02 for Ka-K. The bias in interoccasion variances
      for V and CL appeared to be reduced by compliance estimation while estimates of
      interindividual variability were not affected in a systematic fashion. The bias
      in the residual error variance was decreased from a relative error of about 2 to
      close to 0. The use of hierarchical Bayesian modeling with the incorporation of
      compliance estimation decreased the bias in the typical value parameter but the
      effects on variance parameters were less consistent. The encouraging results of
      these simulation experiments will hopefully stimulate further evaluation of this
      methodology for the estimation of population pharmacokinetic parameters in the
      presence of potential patient noncompliance.

PMID- 12800808
TI  - A joint model for nonlinear longitudinal data with informative dropout.
AB  - Subject withdrawal from a study (also called dropout, or right censoring), is
      common in late phase clinical trials. A number of methods dealing with dropouts
      have been used in practice, the most common being "last observation carried
      forward" (LOCF). Many of these methods, including LOCF, can result in biased
      estimates of the efficacy or potency of the drug, especially in the modeling
      context. If the likelihood of dropout is correlated to the underlying unobserved
      data, the dropout is informative and should not be ignored in the modeling
      process. The topic of informative dropout in the context of longitudinal data has
      received much attention in the statistical literature, in the setting of linear
      and generalized linear models. We extend the approach to nonlinear models. The
      dropout hazard, as well as the longitudinal data, is modeled parametrically.
      Parameters are estimated by maximizing the approximate joint likelihood as
      implemented in the software NONMEM. Using data from actual clinical trials, we
      explore the impact of the dropout model on the ability of the joint model to
      predict observed longitudinal data patterns.

PMID- 12800809
TI  - Alternative therapies: a common practice among men and women living with HIV.
AB  - This study examined the prevalence and factors associated with alternative
      therapy use in an ethnically diverse, gender-balanced sample of persons living
      with HIV/AIDS. More than two thirds (67%) of the participants who were taking HIV
      related medications were also taking an alternative supplement. Half of the
      sample (50%) reported that they took one or more multivitamins, 17% reported
      using mineral supplements, 12% reported using Chinese herbs, and 12% reported
      using botanicals. Substantial proportions of the sample also reported using
      acupuncture (31%), massage (23%), and meditation (28%) to specifically treat HIV
      related symptoms. Women were four times more likely to use alternative therapies
      than men. Also, Caucasians were nearly four times more likely to use alternative
      treatments compared to other ethnic groups. The results of this study indicate a
      strong need to assess individual patients' use of alternative treatment
      approaches as well as to further investigate their efficacy among HIV-positive
      patients.

PMID- 12800810
TI  - Testing strategies to reduce diarrhea in persons with HIV using traditional
      Chinese medicine: acupuncture and moxibustion.
AB  - Diarrhea affects more than 60% of persons living with HIV/AIDS. Diarrhea can be
      caused by pathogens, neoplastic diseases, side effects of medications,
      malabsorption, and/or enteropathy. Activities of daily living and quality of life
      are often affected by HIV/AIDS-related diarrhea. Traditional Chinese medical
      interventions such as acupuncture and moxibustion show promise in the area of
      gastrointestinal symptom management. The purposes of this study were to (a)
      determine the influence of acupuncture and moxibustion in reducing the frequency
      of diarrhea and increasing stool consistency in HIV-infected men with chronic
      diarrhea (defined as three or more episodes of watery, liquid, or loose stools in
      a 24-hour period for 3 weeks or more), (b) ascertain the feasibility of the
      methodology for a future prospective randomized controlled trial, and (c)
      determine sample size estimate for a prospective randomized controlled trial.
      Using a time-series design, 15 HIV-positive men with chronic diarrhea received
      the same acupuncture/moxibustion treatment for six sessions over a 3-week period.
      Each participant maintained a daily stool frequency/consistency and medication
      diary. All treatments were administered by a licensed acupuncturist trained in
      traditional Chinese medicine. Based on the intent to treat analysis comparing the
      change in stool frequency from baseline (Week 1) to Week 3 and Week 4, stool
      frequency reduced approximately one episode per day (Week 3: p < .001; Week 4: p
      < .005). Stool consistency also improved, from baseline to Week 3 and Week 4, by
      more than 1 point on Hansen's stool consistency scale. Acupuncture and
      moxibustion are promising modalities for the symptom management of chronic
      diarrhea in HIV/AIDS. The results of this pilot study also establish the
      feasibility of a larger study and provide the empirical basis to serve as
      preliminary data from which to estimate statistical power and sample size for a
      larger efficacy study, inclusive of women as well as men.

PMID- 12800811
TI  - Factors affecting abnormal Pap smear follow-up among HIV-infected women.
AB  - Women with HIV infection are at least 10 times more likely to have an abnormal
      Pap smear than women who are HIV negative. Unfortunately, many women with HIV do
      not return for care after an abnormal Pap smear. Through the use of focus groups
      and individual interviews, HIV-positive women's experiences with abnormal Pap
      smears and the factors that affected whether they returned for care were
      explored. Two thirds of the 18 participants were minority women, and the average
      age was 40. Using techniques of constant comparative analysis, five factors were
      identified that affected whether women came back for care. These factors included
      fear, the asymptomatic nature of the problem, life circumstances, the
      participant's perspectives on health, and the health care provider. The findings
      from this study have implications for clinical practice and future research
      regarding adherence and abnormal Pap smear follow-up among women with HIV.

PMID- 12800812
TI  - Informal caregivers of persons with HIV/AIDS: a review and analysis.
AB  - Due to advanced antiretroviral treatments, persons with HIV/AIDS (PWH/As) live
      longer and experience various physical and cognitive impairments during the
      course of their disease. Often, informal caregivers assist PWH/As to manage these
      impairments and experience negative physical and psychosocial consequences from
      their role. This article reviews and analyzes published empirical studies that
      have examined physical and psychosocial outcomes in informal caregivers of
      PWH/As. Gaps and limitations of current research are discussed. Recommendations
      for future research and practice implications are also proposed.

PMID- 12800813
TI  - Survey of patient and clinician attitudes on adherence in a rural HIV clinic.
AB  - Adherence is critical to the success of antiretroviral therapy, with near perfect
      medication taking required for optimal results. Many factors may affect a
      patient's ability to adhere to antiretroviral therapy, including complexity of
      the regimen and adverse effects from medications. Previous research showed that
      some disparity may exist between clinicians' and patients' attitudes regarding
      characteristics of a regimen that are likely to affect adherence. The present
      survey was conducted in a rural HIV clinic and confirmed that similar differences
      were present in clinician and patient perceptions of adherence barriers. The
      patient population noted side effects and complexity of schedule as most likely
      to affect adherence, illustrating the need for thorough discussion of new
      regimens and involvement of the patient in treatment decisions.

PMID- 12800814
TI  - Evidence-based practice: what constitutes evidence?

PMID- 12800815
TI  - Food service health inspectors' opinions on the reporting of inspections in the
      media.
AB  - Media reporting of restaurant inspection results is a topic hotly debated by food
      service health inspectors. A survey of Indiana health inspectors was conducted to
      determine attitudes, preferences, and perceptions about the impact of media
      reporting. The survey showed that in the geographic areas of slightly fewer than
      half of the respondents, inspection results were already being reported in the
      media. The question of whether media reporting was advisable received mixed
      responses, with slightly over half favoring media reporting. Respondents were
      more likely to favor media reporting if they were from areas where inspection
      results were already being reported to the media, areas with larger populations,
      or areas in which more restaurant inspections were being done. Newspapers were
      the preferred venue for media reporting.

PMID- 12800816
TI  - Do newspapers lead with lead? A content analysis of how lead health risks to
      children are covered.
AB  - Lead poses a serious environmental health risk to young children, causing such
      irreversible health effects as mental retardation, stunted growth, and hearing
      and visual impairment. Studies suggest that various sectors of the public,
      including children's caregivers, are not sufficiently concerned about this risk
      or knowledgeable about ways of minimizing it. Because newspapers are one of the
      primary ways members of the public learn about risks, the authors examined the
      characteristics and content of 152 newspaper articles on lead to determine when
      coverage occurred and what information was provided. Results revealed that
      newspapers most often covered lead as a local news story. Few articles identified
      children under six years of age as the most vulnerable group or provided
      important information on health effects, sources of exposure, or abatement
      methods. The authors' recommendations focus on helping environmental health
      professionals work with newspaper journalists to improve the information
      available to the public.

PMID- 12800817
TI  - The Welsh Food Microbiological Forum and the All-Wales Shopping Basket Sampling
      Program: a model for the surveillance of microbiological quality in ready-to-eat
      foods.
AB  - In the United Kingdom, the monitoring of microbiological food quality and the
      prevention of foodborne disease are the responsibility of a number of different
      organizations. In 1993, to develop and extend ongoing local collaborations within
      selected local food groups in Wales (comprising local authorities and the Public
      Health Laboratory Service), the Welsh Office invited all local food groups in
      Wales to create a forum to coordinate the sampling and examination of ready-to
      eat foods and the centralized collection of results for the whole of Wales. This
      paper describes the development, structure, and aims of the forum. It also
      discusses the outcomes of the first nine years of activities, describes the
      randomized sampling program for ready-to-eat foods that has been developed; and
      assesses the benefits that have resulted.

PMID- 12800818
TI  - Language and the law.

PMID- 12800819
TI  - Efflorescence.

PMID- 12800820
TI  - Impact of HAART on HIV-linked malignancies.

PMID- 12800821
TI  - Tuberculosis: first new guidelines since 1994.

PMID- 12800822
TI  - Study looks at how HIV may spread through oral sex.

PMID- 12800823
TI  - Pulmonary hypertension and HIV.

PMID- 12800824
TI  - Merging clinical performance and quality assurance in ambulatory HIV care: Part
      2, outcomes.

PMID- 12800825
TI  - Where now for Trizivir? Role of the triple-NRTI pill post-ACTG 5095.

PMID- 12800826
TI  - Treating HIV infection and AIDS in women.

PMID- 12800827
TI  - Women with HIV/AIDS: treating the fastest-growing population.
AB  - AIDS is essentially the same disease in men and women, but a combination of
      social, psychological, and physiologic factors appear to define HIV disease and
      AIDS in women and suggest that different approaches may be needed for female
      patients. The likelihood that a woman will receive, adhere to, and respond to
      antiretroviral therapy differs from that among men. Specific psychosocial issues
      serve as barriers to treatment and adherence in women. Gender differences in CD4+
      counts and viral load may warrant revisions of standard treatment guidelines,
      which were originally developed for men. Physicians need to understand gender
      differences in the course of AIDS, treatment responses, and the efficacy of newer
      antiretroviral drugs. Earlier diagnosis of HIV infection and AIDS in women may
      hinge on recognition of gender-specific AIDS-defining illnesses. Development of
      once-daily, tolerable, safer pharmacologic agents with distinct resistance
      profiles might improve adherence and efficacy of treatment in both men and women.

PMID- 12800828
TI  - [A survey of the studies on saponins from Bupleurum in past 10 years].

PMID- 12800829
TI  - Hyperglycemia and oxidative stress: complex relationships with attractive
      prospects.

PMID- 12800830
TI  - Contemporary issues in women's health.

PMID- 12800831
TI  - Pulmonary vascular resistance.  A meaningless variable?

PMID- 12800832
TI  - ACOG committee opinion. Number 281, December 2002. Rubella vaccination.

PMID- 12800833
TI  - Dandy-Walker complex and syringomyelia in an adult: case report and discussion.

PMID- 12800834
TI  - Immediate neurocognitive effects of concussion: graded contusion model of the
      mouse spinal cord using a pneumatic impact device.

PMID- 12800835
TI  - [Transfusion with fresh frozen plasma: products, indications].

PMID- 12800836
TI  - [Expanded inpatient care capacity for psychosomatics? German states in conflict
      with their own expert advisors].

PMID- 12800837
TI  - Clinical and radiographic outcome in the management of posterior circulation
      aneurysms by use of direct surgical or endovascular techniques.

PMID- 12800838
TI  - [Off-label use in psychopharmacotherapy. Letter to Federal Minister Ulla Schmidt,
      Pulheim, 22 January 2003].

PMID- 12800839
TI  - A cost-effectiveness analysis of endoscopic third ventriculostomy.

PMID- 12800840
TI  - [Statement of the DGPPN on the key policy points of the German Federal Ministry
      of Health and Social Security with regard to modernization of the health care
      system].

PMID- 12800841
TI  - Brain oxygenation and energy metabolism: Part 1--Biological function and
      pathophysiology.

PMID- 12800842
TI  - Operative nuances of myelomeningocele closure.

PMID- 12800843
TI  - Unusual migration of the distal catheter of a ventriculoperitoneal shunt into the
      heart: case report.

PMID- 12800844
TI  - Preoperative evaluation of neurovascular compression in patients with trigeminal
      neuralgia by use of three-dimensional reconstruction from two types of high
      resolution magnetic resonance imaging.

PMID- 12800845
TI  - Endoscopically assisted transoral-transpharyngeal approach to the craniovertebral
      junction.

PMID- 12800846
TI  - Minimally invasive percutaneous posterior lumbar interbody fusion.

PMID- 12800848
TI  - [Proceedings of the 24th Munich Symposium for Experimental Orthopedics. Munich,
      Germany, February 2002].

PMID- 12800847
TI  - The genesis of neurosurgery and the evolution of the neurosurgical operative
      environment: Part 1--Prehistory to 2003.

PMID- 12800849
TI  - [Evaluation of practice].

PMID- 12800850
TI  - [The Greek illustrations of the human diseases: Mount Athos].
AB  - Philippe Charlier deals with the whole illustrations of human diseases either
      from religious texts or works of art. He tends to pass in review the skeletal and
      anatomic illustrations of the illness which has been a repetitive subject since
      the ancient Greeks. The author points out their common features and their amazing
      differences in the examples of Mount Athos.

PMID- 12800851
TI  - [The didactical poem in medical education].

PMID- 12800852
TI  - [Internal medicine in Hungary, between 1919 and 1945].
AB  - Author gives a comprehensive overview of the development of internal medicine in
      Hungary in the inter-war period (1919-1945). Based mostly on articles published
      in contemporary Hungarian medical journals, he analyses the activities of the
      different specialties, follows, evaluates and summarizes the development of the
      individual fields of research. After the detailed chronological presentation
      author concludes that Hungarian internal medicine in the pre-war period matched
      or sometimes even exceeded the level of the age.

PMID- 12800853
TI  - [Theoretic medicine in Egypt].
AB  - Egyptian medical writings - especially those surviving on papyri - provide a rich
      material for historical research. They did not only serve the memory of old
      healing methods and practices, but that of contemporary medical theories and
      views as well. On the one hand, Egyptians knew illnesses caused by factors
      physicians could easily identify by mere empirism, or by their anatomical or
      physiological knowledge. (Their main physiological theory was probably based on
      the idea of specific materials circulating through a system of canals (mtw) in
      the body. It produced illness, either by the system being blocked, or by its
      original materials changed into the pathogenic material (wxdw). On the other hand
      however, they supposed the existence of illnesses, caused by the activity of
      supernatural forces or demons. The two different but parallel etiologies demanded
      different therapies. Consequently, besides physical also magical therapies were
      used, and in the healing process the healer him/herself played a double role.
      Egyptian thinking regarded both ways of healing - the physical and the magical -
      as equally useful and rational. This richly documented article gives an overview
      of the Egyptian medical heritage, as illustrated by the original texts and
      objects.

PMID- 12800854
TI  - [Garri Izrailevich Abelev--on his 75th birthday. A few words about G I Abelev].

PMID- 12800855
TI  - [Georgii Pavlovich Georgiev--on his 70th birthday].

PMID- 12800856
TI  - Bibliography. Current Literature. Glaucoma.

PMID- 12800857
TI  - Expert consensus document on management of cardiovascular diseases during
      pregnancy.

PMID- 12800858
TI  - Prediction of body fat from skinfolds: the importance of including sites from the
      lower limb.

PMID- 12800859
TI  - The influence of a 6.5% carbohydrate-electrolyte solution on performance of
      prolonged intermittent high-intensity running at 30 degrees C.
AB  - Nine male student games players consumed either flavoured water (0.1 g
      carbohydrate, Na+ 6 mmol x l(-1)), a solution containing 6.5% carbohydrate
      electrolytes (6.5 g carbohydrate, Na+ 21 mmol x l(-1)) or a taste placebo (Na+ 2
      mmol x l(-1)) during an intermittent shuttle test performed on three separate
      occasions at an ambient temperature of 30 degrees C (dry bulb). The test involved
      five 15-min sets of repeated cycles of walking and variable speed running, each
      separated by a 4-min rest (part A of the test), followed by 60 s run/60 s rest
      until exhaustion (part B of the test). The participants drank 6.5 ml x kg(-1) of
      fluid as a bolus just before exercise and thereafter 4.5 ml x kg(-1) during every
      exercise set and rest period (19 min). There was a trial order effect. The total
      distance completed by the participants was greater in trial 3 (8441 +/- 873 m)
      than in trial 1 (6839 +/- 512, P < 0.05). This represented a 19% improvement in
      exercise capacity. However, the trials were performed in a random counterbalanced
      order and the participants completed 8634 +/- 653 m, 7786 +/- 741 m and 7099 +/-
      647 m in the flavoured water (FW), placebo (P) and carbohydrate-electrolyte (CE)
      trials, respectively (P = 0.08). Sprint performance was not different between the
      trials but was impaired over time (FW vs P vs CE: set 1, 2.41 +/- 0.02 vs 2.39 +/
      0.03 vs 2.39 +/- 0.03 s; end set, 2.46 +/- 0.03 vs 2.47 +/- 0.03 vs 2.47 +/-
      0.02 s; main effect time, P < 0.01). The rate of rise in rectal temperature was
      greater in the carbohydrate-electrolyte trial (rise in rectal
      temperature/duration of trial, degrees C x h(-1); FW vs CE, P < 0.05; P vs CE,
      N.S.). Blood glucose concentrations were higher in the carbohydrate-electrolyte
      than in the other two trials (FW vs P vs CE:rest, 4.4 +/- 0.1 vs 4.3 +/- 0.1 vs
      4.2 +/- 0.1 mmol x l(-1); end of exercise, 5.4 +/- 0.3 vs 6.4 +/- 0.6 vs 7.2 +/-
      0.5 mmol x l(-1); main effect trial, P < 0.05; main effect time, P < 0.01).
      Plasma free fatty acid concentrations at the end of exercise were lower in the
      carbohydrate-electrolyte trial than in the other two trials (FW vs P vs CE: 0.57
      +/- 0.08 vs 0.53 +/- 0.11 vs 0.29 +/- 0.04 mmol x l(-1); interaction, P < 0.01).
      The correlation between the rate of rise in rectal temperature (degrees C x h(
      1)) and the distance completed was -0.91, -0.92 and -0.96 in the flavoured water,
      placebo and carbohydrate-electrolyte conditions, respectively (P < 0.01). Heart
      rate, blood pressure, plasma ammonia, blood lactate, plasma volume and rate of
      perceived exertion were not different between the three fluid trials. Although
      drinking the carbohydrate-electrolyte solution induced greater metabolic changes
      than the flavoured water and placebo solutions, it is unlikely that in these
      unacclimated males carbohydrate availability was a limiting factor in the
      performance of intermittent running in hot environmental conditions.

PMID- 12800861
TI  - Role ambiguity and athlete satisfaction.
AB  - The aim of this study was to examine the relationship between athletes'
      perceptions of role ambiguity and satisfaction. The relationship between these
      multidimensional constructs was investigated at the beginning and at the end of
      the season, as well as from early season to end of season. Consistent with the a
      prioi hypothesis, concurrent analyses revealed lower perceived role ambiguity was
      associated with higher athlete satisfaction. Specifically, role ambiguity, as
      represented by the dimension Scope of Responsibilities on offence, was
      significantly related to the leadership facets of athlete satisfaction (i.e.
      ability utilization, strategy, and training/instruction) both at the beginning
      and at the end of the season. However, contrary to expectations, role ambiguity
      at the beginning of the season was not predictive of athlete satisfaction at the
      end of the season. The implications of the results are discussed and future
      research is suggested.

PMID- 12800860
TI  - Influence of different types of exercise on the expression of haem oxygenase-1 in
      leukocytes.
AB  - Haem-oxygenase-1 (HO-1) is an antioxidant stress protein that is mainly induced
      by reactive oxygen species, inflammatory cytokines and hyperthermia. We assessed
      the influence of different types of exercise on HO-1 expression in leukocytes of
      the peripheral blood in three groups of male participants: a short exhaustive run
      above the lactate steady state (n = 15), eccentric exercise (n = 12) and an
      intensive endurance run (half-marathon, n = 12). Blood samples were taken at rest
      and up to 24 h after exercise. Blood lactate concentration after exercise was 9.0
      +/- 2.1, 3.8 +/- 1.6 and 5.1 +/- 2.2 mmol x l(-1) (mean +/- s) for the exhaustive
      run, eccentric exercise and half-marathon groups, respectively (P < 0.05).
      Creatine kinase concentration was highest 24 h after exercise: 133 +/- 91, 231 +/
      139 and 289 +/- 221 U x l(-1) for the exhaustive run, eccentric exercise and
      half-marathon groups, respectively (P < 0.05). The maximal increase in leukocyte
      counts after exercise was 11.5 +/- 19.2, 6.2 +/- 1.4 and 14.7 +/- 2.1 x 10(9) x
      l(-1). There was no change in HO-1 as a result of the short exhaustive run or the
      eccentric exercise, whereas the half-marathon had a significant stimulatory
      effect on HO-1-expression in lymphocytes, monocytes and granulocytes (P < 0.001)
      using flow cytometry analyses. In conclusion, eccentric exercise alone or short
      term heavy exercise are not sufficient to stimulate the antioxidative stress
      protein HO-1 in peripheral leukocytes

PMID- 12800862
TI  - Neuromuscular variables affecting the magnitude of force loss after eccentric
      exercise.
AB  - The aim of this study was to examine neuromuscular variables contributing to
      differences in force loss after participants were exposed to the same relative
      bout of eccentric exercise. Thirty-six males performed 50 maximal eccentric
      contractions of the elbow flexors and were stratified into high responders (n =
      10) and low responders (n = 10) based on force loss 36 h after exercise. Maximal
      voluntary isometric contractions (MVCs) and electromyography (EMG) were measured
      at baseline and 36 h after exercise. During eccentric exercise, mean peak torque,
      mean end-range torque from the final 25% of each trial and total angular impulse
      were computed over 25 contractions in each of two bouts. The slope of the change
      in these values for each 25 eccentric contractions was calculated for each
      participant using linear regression. At baseline, MVC was not different between
      groups (low responders: 97.0 +/- 9.6 N x m; high responders: 82.7 +/- 6.4 N x m;
      P = 0.08). High responders demonstrated a 68% (range 62-78%) reduction in MVC and
      low responders a 39% (29-48%) reduction after exercise. Peak torque, end-range
      torque and total angular impulse were 13%, 40% and 33% higher, respectively, in
      the low than in the high responders (peak torque: P = 0.0002; end-range torque: P
      < 0.0001; total angular impulse: P < 0.001). The rate of decline in peak torque
      slope was greater in high than in low responders (P = 0.044). In conclusion,
      lower peak torque, end-range torque and total angular impulse during eccentric
      contractions and a greater peak torque slope may identify high responders to
      eccentric exercise.

PMID- 12800863
TI  - A comparison of the cycling performance of cyclists and triathletes.
AB  - The aim of this study was to compare the cycling performance of cyclists and
      triathletes. Each week for 3 weeks, and on different days, 25 highly trained male
      cyclists and 18 highly trained male triathletes performed: (1) an incremental
      exercise test on a cycle ergometer for the determination of peak oxygen
      consumption (VO2peak), peak power output and the first and second ventilatory
      thresholds, followed 15 min later by a sprint to volitional fatigue at 150% of
      peak power output; (2) a cycle to exhaustion test at the VO2peak power output;
      and (3) a 40-km cycle time-trial. There were no differences in VO2peak, peak
      power output, time to volitional fatigue at 150% of peak power output or time to
      exhaustion at VO2peak power output between the two groups. However, the cyclists
      had a significantly faster time to complete the 40-km time-trial (56:18 +/- 2:31
      min:s; mean +/- s) than the triathletes (58:57 +/- 3:06 min:s; P < 0.01), which
      could be partially explained (r = 0.34-0.51; P < 0.05) by a significantly higher
      first (3.32 +/- 0.36 vs 3.08 +/- 0.36 l x min(-1)) and second ventilatory
      threshold (4.05 +/- 0.36 vs 3.81 +/- 0.29 l x min(-1); both P < 0.05) in the
      cyclists compared with the triathletes. In conclusion, cyclists may be able to
      perform better than triathletes in cycling time-trial events because they have
      higher first and second ventilatory thresholds.

PMID- 12800864
TI  - Neural adaptations with sport-specific resistance training in highly skilled
      athletes.
AB  - The aim of this study was to assess the effects of variations in the volume and
      intensity of resistance training in highly skilled athletes on neural adaptive
      mechanisms: the maximality and pattern of neural drive. The maximality of muscle
      activation was measured using a high-resolution sample and hold amplifier to
      record interpolated twitches. The pattern of neural drive was measured by
      analysing isometric torque-time curves and electromyographic (EMG)
      characteristics during the performance of rapid isometric contractions at maximal
      effort. The volume and intensity of training were varied at 4-weekly intervals to
      systematically emphasize the development of strength, power and motor performance
      in 14 highly skilled track and field athletes (e.g. discus, hammer, javelin, shot
      put and weight). Knee extension strength increased significantly by 15% during
      steady maximal isometric contractions and by 24% during rapid isometric
      contractions at maximal effort after the 16-week training programme (P < 0.05).
      Increases in EMG amplitude and rate of EMG activation indicated that improvements
      to the pattern of neural drive occurred with sport-specific resistance training
      (P < 0.05). The maximality and pattern of neural drive did not change in the
      control group.

PMID- 12800865
TI  - British running performances in the eighteenth century.
AB  - Our aims were to improve our understanding of human performance before 1850 and
      to put nineteenth- and twentieth-century performances into a broader historical
      context. Consequently, 536 foot-races performed in Britain in the 'long'
      eighteenth century were identified, 53 of which were analysed in detail. The best
      performances at the end of the eighteenth century were compared with those at the
      end of the nineteenth and twentieth centuries. The data for the nineteenth
      century were marginally better than those for the eighteenth century up to 20 nm,
      but beyond that Thomas Carlisle's time, set in about 1740, of 2 hours for 21
      miles was outstanding. Current records are shown to be better than earlier
      records at all distances from 5 km up to the marathon, the superiority being most
      pronounced from 15 km upwards.

PMID- 12800866
TI  - Intramammary pressure in the lactating sow in response to oxytocin and during
      natural milk ejections throughout lactation.
AB  - We developed a simple, non-invasive method to measure the intramammary pressure
      (IMP) response in sows during natural milk ejection and after i.v. injections of
      oxytocin. The teats of sows were cannulated and the amplitude and duration of IMP
      changes were measured via a pressure transducer linked to a computer. During
      natural milk ejections, the amplitude of the response was 5.5+/-1.8 kPa (mean +/-
      SD) and the duration of response at half the peak amplitude was 6.8+/-1.6 s. In
      response to oxytocin a threshold response occurred at 60 mIU oxytocin with no
      further change up to 200 mIU. The amplitude of the response to an i.v. dose of 60
      200 mIU oxytocin (5.5+/-2.2 kPa) and duration (6.4+/-1.7 s) were similar to that
      during a natural milk ejection. The responses of two galactophorous ducts of a
      teat measured simultaneously were similar in peak amplitude and duration. When
      the responses of four glands of a sow were measured simultaneously, there was a
      lag time in the onset of the IMP peak from the anterior to the posterior glands,
      and an increase in the peak amplitude from anterior to posterior. Both during
      natural milk ejections and in response to oxytocin injections, there were
      significant differences in peak amplitude between sows. We also aimed to
      determine whether the pressure or duration of milk flow during natural milk
      ejections was limiting piglet growth rates. IMP of nine sows and the growth rates
      of their piglets were measured. Both the peak amplitude of IMP response and the
      growth rate of piglets increased over the course of lactation, but the
      relationship was not causal. We found that the growth rate of piglets did not
      depend on IMP amplitude or duration, but we suggest that it may depend on the
      frequency of suckling and/or the ability of piglets to withdraw milk while it is
      available.

PMID- 12800867
TI  - Evaluation of diagnostic procedures for subclinical mastitis in meat-producing
      sheep.
AB  - Samples of foremilk were collected from 261 clinically normal glands of 150 ewes,
      and tested using the California mastitis test (CMT). Further samples were
      collected from 195 of these glands for determination of automated somatic cell
      counts (SCC), and from 60 of these glands for bacteriological assessment. The
      sensitivity and specificity of CMT for detecting samples with SCC above different
      threshold levels and for CMT and SCC in determining bacteriological status were
      evaluated using two-graph receiver operating characteristics (TG-ROC). Milk
      samples were obtained subsequently from ten CMT positive, and five CMT negative
      first- and second-lactation ewes. Samples were cultured using a variety of media,
      incubation temperatures and atmospheric conditions, immediately after collection,
      and 1 week after storage at 4 degrees C and -21 degrees C. Results suggested that
      CMT is best used as a diagnostic test for ovine subclinical mastitis (SCM) with a
      cut-off of 3 (distinct gel formation), and that automated SCC thresholds of >
      1200 x 10(3) cells/ml are appropriate, especially where low prevalences are
      expected (e.g. < 5%). Additionally, this study showed that routine
      bacteriological methods were appropriate for isolation of most species of
      pathogen responsible for ovine SCM, but storage of samples prior to culture,
      either at 4 degrees C or -21 degrees C, was detrimental to the isolation of
      several of these organisms.

PMID- 12800868
TI  - Multiplex polymerase chain reaction as a mastitis screening test for
      Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae and
      Streptococcus uberis in bulk milk samples.
AB  - Effective diagnostic tools for screening herds for mastitis pathogens are
      important in development and monitoring of mastitis control programmes. A
      multiplex polymerase chain reaction (PCR) assay for simultaneous detection of
      Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae and
      Streptococcus uberis was used in preliminary studies to assess its applicability
      as an alternative method for monitoring mastitis caused by these organisms at the
      herd level. PCR was used to detect the presence of these organisms in bulk milk
      samples. Correlations with bulk milk somatic cell counts (BMCC), total bacteria
      counts and thermoduric bacteria counts were evaluated. A total of 176 bulk milk
      samples were collected from 42 herds on five consecutive occasions at approx. 10
      d intervals. Str. uberis was the most common organism in these bulk milk samples.
      There was no relationship between presence of either Staph. aureus, Str.
      dysgalactiae or Str. uberis and BMCC, total bacteria counts or thermoduric
      bacteria counts. However, presence of Str. agalactiae was associated with high
      BMCC and total bacteria counts. The results of this study show that regular
      analysis of bulk milk using this multiplex PCR assay may be a useful tool for
      monitoring herd status with respect to Str. agalactiae, but is of less value for
      monitoring occurrence of Staph. aureus, Str. dysgalactiae and Str. uberis.
      Further investigations are needed to clarify the relationship between positive
      PCR results and the prevalence of infected cows in the herd.

PMID- 12800869
TI  - Dynamics of experimentally induced Staphylococcus epidermidis mastitis in East
      Friesian milk ewes.
AB  - The responses of five lactating East Friesian milk ewes to experimental mammary
      infection with Staphylococcus epidermidis and of five control ewes were examined
      over a period of 10 weeks. Infection caused an influx of neutrophils into milk,
      the numbers of which started to rise 4 h post infection and peaked 24 h after
      infection. The initial response was accompanied by mild fever and mild
      leucopaenia in blood (8 h after infection). No other signs of systemic infection
      were observed. Milk appeared normal at all times, although the milk yield of
      infected ewes tended to decline. Staphylococci were absent in milk from four ewes
      at 2 d and at 3 d after infection, but re-emerged intermittently in four of five
      ewes at subsequent samplings. Cytokines in milk were measured by ELISA. IL-8 was
      elevated in infected glands at 2 h and peaked at 8 h. In the four ewes
      intermittently shedding bacteria, IL-8 remained elevated until the final sampling
      at 10 weeks. IL-1beta was transiently elevated at 1 d and 2 d and showed a
      pronounced peak in one sheep. Milk samples from this ewe were bacteriologically
      negative, somatic cell count (SCC) was within the normal range and the
      concentrations of IL-1beta, as well as IL-8, were similiar to the control group
      (n=5) from 1 week after infection until the final sampling. Histological
      examination revealed leucocytic infiltrates in the four glands remaining infected
      at the end of the experiment, and a high level of CD5+ lymphocytes in three ewes.
      The results suggest that the relationship between the initial neutrophil influx
      and the proinflammatory cytokines may be responsible for determining the course
      of infection. Subclinical mastitis due to coagulase-negative staphylococci leads
      to minor changes in milk yield and milk constituents.

PMID- 12800870
TI  - Immunomodulatory consequences of oral administration of Lactobacillus rhamnosus
      strain GG in healthy volunteers.
AB  - Probiotic microorganisms, especially lactic acid bacteria, are effective in the
      treatment of infectious diarrhoeal diseases and experimental colitis. Although
      the mechanisms by which these organisms exert their anti-inflammatory effects are
      largely unknown, immunomodulating effects are suggested. The objective of this
      study was to examine the effect of a 5-week oral administration of Lactobacillus
      rhamnosus subspecies GG (Lb. GG) on the cellular immune response to intestinal
      microorganisms in ten healthy volunteers. Peripheral blood cells (PB) were
      stimulated with either 'self' or 'non-self' preparations of faecal samples and
      isolated Bacteroides fragilis group-organisms (Bfg) or Escherichia coli (Esch.
      coli), and pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-gamma,
      TNF-alpha) were measured in the culture supernatant. CD4+ T-lymphocyte activation
      was determined by measurement of intracellular ATP following lysis of the cells.
      The activational response of CD4+ T-lymphocytes towards isolated and heat
      inactivated intestinal organisms was increased after the probiotic treatment.
      Additionally, TNF-alpha, IL-6 and in part IFN-gamma cytokine secretion by PB
      cells following stimulation with whole stool preparations and single members of
      the flora was significantly decreased, whereas the IL-10 and in part IL-4
      cytokine secretion was increased at the end of the study. In contrast, the
      activational response of CD4+ T-lymphocytes following stimulation with whole 'non
      self' intestinal flora was higher than by 'self' intestinal flora, but both
      responses showed a trend towards a reduction at the end of the study. This study
      documents a direct effect by Lb. GG on the cellular immune system of healthy
      volunteers and offers a promising tool to investigate systemic immunomodulation
      due to oral administration of probiotic microorganisms.

PMID- 12800871
TI  - No difference in symptoms during challenges with homogenized and unhomogenized
      cow's milk in subjects with subjective hypersensitivity to homogenized milk.
AB  - It has been hypothesized that certain consumers tolerate untreated cow's milk,
      but react to processed (i.e. homogenized and pasteurized) cow's milk although
      they do not suffer from IgE-mediated cow's milk allergy or lactose intolerance.
      The aim of the study was to compare the tolerance of unhomogenized and
      homogenized cow's milk in lactose tolerant adults who had repeatedly experienced
      better tolerance of unhomogenized than homogenized milk. Forty-four subjects were
      challenged with homogenized and unhomogenized cow's milk for five days in a
      randomized, double-blind, cross-over study. No differences in the symptoms during
      the challenges were found. Roughly half the subjects tolerated the homogenized
      milk better and the other half tolerated the unhomogenized milk better. The
      results of this study show no difference in the tolerance of homogenized and
      unhomogenized milk in adults with self-reported symptoms suggestive of
      hypersensitivity to homogenized milk.

PMID- 12800872
TI  - Effect of dietary inclusion of goat milk on the bioavailability of zinc and
      selenium in rats.
AB  - The effects of dietary inclusion of freeze-dried goat and cow milk on the
      utilization of zinc and selenium, and on the metabolic fate of zinc, were studied
      in transected (control) and resected rats (resection of 50% of the distal small
      intestine). Intestinal resection reduced the apparent digestibility coefficient
      and zinc retention in the cow milk diet, whereas these biological indices were
      similar in transected (control) and resected rats with standard (without milk)
      and goat milk diets. The apparent digestibility coefficient and retention of
      selenium were not affected by intestinal resection in the animals fed with the
      three diets studied. In transected (control) and resected rats, the apparent
      digestibility coefficient and retention of zinc and selenium were higher for the
      goat milk diet than for the other two diets. Zinc deposits in the organs,
      expressed as microg/g dry weight were in order of decreasing concentrations:
      femur, testes, sternum, liver, kidney, heart, spleen, longissimus dorsi muscle
      and brain. Deposits were greatest with the goat milk diet, followed by the
      standard diet and were lowest for the rats given the cow milk diet, both for
      transected (control) and resected animals. We conclude that consumption of the
      goat milk diet produces a greater bioavailability of zinc and selenium and a
      greater deposit of zinc in key organs, for both the transected (control) and the
      resected rats, with respect to the standard diet and the cow milk diet.

PMID- 12800873
TI  - Antibacterial activity of casein-derived peptides isolated from rabbit
      (Oryctolagus cuniculus) milk.
AB  - Acid-precipitated rabbit 'whole casein' was digested by trypsin, chymotrypsin,
      pepsin, and clostripain to screen for possible peptides with antibacterial
      properties. The peptide fragments were separated by reversed-phase
      chromatography. The collected fractions were pooled and their antibacterial
      properties tested against Escherichia coli, Bacillus subtilis and Staphylococcus
      lentus. Three antibacterial peptide fragments derived from tryptic digestion of
      rabbit casein were isolated and identified. Their sequences were found as
      follows: HVEQLLR (residues 50-56 of beta-casein), ILPFIQSLFPFAER (residues 64-77
      of beta-casein), and FHLGHLK (residues 19-25 of alpha(s1)-casein). The three
      peptides were synthesized and found to exert antibacterial effect against gram
      positive bacteria only. Proteolytic digestion of rabbit casein by chymotrypsin,
      pepsin and clostripain yielded several peptide fragments with antibacterial
      activity. Since antibiotic peptides can be released from casein during the
      digestion of milk proteins, our results suggest a possible antibacterial function
      of rabbit caseins. It is conceivable that antibacterial peptides can be generated
      by endopeptidases of the mammalian gastrointestinal tract possibly providing
      protection for new-born rabbits against aggression of micro-organisms.

PMID- 12800874
TI  - Chromosomal location of the genetic determinants for bacteriocins produced by
      Lactobacillus gasseri K7.
AB  - The production of similar or even identical bacteriocins by different lactic acid
      bacteria is not a rare event. To take advantage of this finding, genetic
      determinants of the Lactobacillus K7 bacteriocins were tested for putative
      homologies with previously described bacteriocins of the Lactobacillus
      acidophilus group through polymerase chain reaction (PCR). Among specific primer
      pairs of seven known bacteriocins, derived from their respective sequences, only
      acidocin LF221 A and B primers amplified fragments in chromosomal DNA of K7
      strain that revealed strong similarity over small regions of LF221 bacteriocins.
      Treatment of Lactobacillus K7 with ethidium bromide and mitomycin C was
      ineffective in generating non-bacteriocinogenic derivatives and had no impact on
      plasmid loss either. Classification studies elucidated Lactobacillus K7 as a
      member of the Lactobacillus gasseri species.

PMID- 12800875
TI  - Effect of protein and temperature on cutting time prediction in goats' milk using
      an optical reflectance sensor.
AB  - An objective method for determining the coagulum cutting time is needed to
      improve consistency and processing efficiency of goats' cheese. A fibre optic
      sensor was used to measure the backscatter of near-infrared radiation at 880 nm
      during the coagulation of skimmed goats' milk for the purpose of predicting
      coagulum cutting time. A randomised block design, replicated three times, was
      used to test the effect of three protein concentrations (3, 5 and 7% (w/w)) on
      diffuse reflectance parameters for cutting time prediction of milk coagulated at
      five different temperatures (20, 25, 30, 35 and 40 degrees C) to assure a wide
      range of coagulation rates. The inclusion of a protein term in the existing
      algorithms was essential to reduce the standard error of prediction to under 6.2
      min. An algorithm including a time-based parameter and a protein term, Tcut=beta0
      T2min (1 + gamma% Protein) was found to predict cutting time with a SEP of 2.42
      min and an R2 of 0.98. Gamma was considered constant (gamma=-0.0674, goats' milk)
      representing the protein effect on beta0. Algorithms using response-based
      parameters (such as change in reflectance ratio) and the composition parameter
      protein required additional regression parameters such as temperature and an
      intercept term to predict the cutting time with the same precision as algorithms
      using only time-based parameters. Time-based parameters were found to decrease
      proportionally with increasing temperature and decreasing protein concentration.
      Response-based and mixed-based parameters were found to decrease with decreasing
      temperature. Reflectance ratio at cutting time did not significantly change with
      protein concentration for skimmed goats' milk. The activation energy of kappa
      casein hydrolysis was calculated based on changes in reflectance profile
      parameters and was found to be in the range 63-72 kJ mol(-1).

PMID- 12800876
TI  - Influence of seasonal variation on kinetics of time temperature integrators for
      thermally processed milk.
AB  - In the context of identifying intrinsic time temperature integrators (TTIs) for
      evaluating thermal processing of milk, the possible influence of seasonal
      variation in milk composition on the applicability of alkaline phosphatase (ALP),
      hydroxymethylfurfural (HMF), lactulose and furosine for process impact assessment
      was studied. Hereto inactivation and formation kinetics of these indicators were
      analysed in milk samples collected over a one year period. Based on previous
      research (isothermal and non-isothermal heating conditions) it was assumed that
      thermal inactivation of ALP followed first order kinetics, and formation of HMF,
      lactulose and furosine could be described by pseudo-zero order kinetics. This
      allowed the use of a simplified experimental design to obtain the kinetic
      parameters. Based on 90% joint confidence regions, kinetic parameter values
      differed significantly between different batches of milk for all four indicators.
      Additionally, variable ALP activities and HMF concentrations were observed in the
      raw milk samples. Nevertheless, the observed differences did not seem to restrict
      the applicability of the selected TTIs as illustrated by the construction of
      temperature time tolerance (TTT-) diagrams. Through these diagrams, use of the
      TTIs implied an uncertainty of approximately 2 degrees C between equivalent
      processes.

PMID- 12800877
TI  - Effects of lactoperoxidase and hydrogen peroxide on rheological properties of
      yoghurt.
AB  - The effects of activation of the lactoperoxidase (LPO) system by H2O2-NaSCN and
      hydrogen peroxide (H2O2) on the accessibility of sulphydryl groups (SH) in
      skimmed milk, and on the dynamic rheological properties of the resulting yoghurt
      were investigated. Four different concentrations of each reagent (20-80 mg H2O2
      NaSCN/kg milk and 100-400 mg H2O2/kg milk) were compared. Clear negative
      correlations were noted between the accessibility of SH groups and both LPO
      activation rate and H2O2 concentration. Also the native PAGE pattern of the heat
      treated samples showed that with increase in the H2O2-NaSCN and H2O2
      concentrations, the level of interaction between beta-lactoglobulin (beta-lg) and
      kappa-casein (kappa-CN) decreased. The complex modulus (G*) of skimmed milk
      yoghurts declined gradually with the decrease in the concentration of accessible
      SH groups accordingly. Tan delta values of yoghurt samples were found to be
      different from the control, but close to each other, indicating that protein
      interaction forces taking place in the formation of gel networks of treated
      yoghurts were different from the control.

PMID- 12800878
TI  - Prevalence of intramammary infections by major pathogens at parturition in dairy
      cows after intramuscular antibiotic therapy at drying-off: a preliminary report.

PMID- 12800879
TI  - Molecular characterization of the goat CSN1S1(01) allele.

PMID- 12800880
TI  - Use of an ion-selective electrode to determine free Ca ion concentration in the
      milk of various mammals.

PMID- 12800881
TI  - Detection of Brucella spp. in soft cheese by semi-nested polymerase chain
      reaction.

PMID- 12800882
TI  - Catabolism of aromatic amino acids in cheese-related bacteria: aminotransferase
      and decarboxylase activities.

PMID- 12800883
TI  - Heat induced gelation of acid milk: balance between weak and covalent bonds.

PMID- 12800884
TI  - Winners and losers in flexible labor markets: the fate of women with chronic
      illness in contrasting policy environments--Sweden and Britain.
AB  - This study compares employment rates among men and women with and without chronic
      illness in the contrasting policy environments of Britain and Sweden, through
      analysis of household surveys for 1979-1995. Professional and managerial groups
      were winners in both countries, including during recession. By the 1990s,
      employment rates for healthy Swedish women were uniformly high across the social
      groups and almost comparable with those of their male counterparts; rates for
      women and men with a chronic illness were also comparable, albeit at a lower
      overall rate. The greatest losers were male and female unskilled manual workers
      in Britain. British women with a chronic illness in the 1990s had less than half
      the employment rates of healthy women. Such social inequalities were much smaller
      and less consistent in Sweden, where the impact of illness was softened for all
      social groups. In Britain, workless men tended to be classed as unemployed or
      permanently sick, while workless women were more likely to be classed as looking
      after home/family. Lesser differences were seen in Sweden. No evidence was found
      to support the hypothesis that women in general, and the less skilled and sick in
      particular, would be the winners in a more flexible, less regulated labor market
      quite the reverse.

PMID- 12800885
TI  - Radical changes or traditional approaches in a different guise? An analysis of
      the Norwegian mother-child service.
AB  - In recent years practitioners within the Norwegian mother and child health
      service have been advised to change their approach to parents, and in particular
      to play down their traditional "expert" role. On matters concerning their own
      child, parents have come to be regarded as the "experts," and scientific
      knowledge is no longer considered superior to skills gained through practical
      experience. However, current recommendations for practice are inconsistent, and
      rather than being reduced, professional authority and control have entered a new
      mode. Instead of being articulated and made explicit these aspects of the mother
      child service are disguised. The language employed by the service might act to
      mask attempts to maintain the traditional relationship between professionals and
      parents. This article does not direct a one-sided critique toward the exercise of
      professional authority within this field of practice, but instead seeks to
      initiate a discussion on legitimate and illegitimate forms of authority and
      control. The analysis draws on two sources of data: documentary materials and
      interviews with public health nurses.

PMID- 12800886
TI  - Son preference, sex selection, and the "new" new reproductive technologies.
AB  - Throughout recorded history, humans have tried to influence the sex of their
      offspring, through pregnancy injunctions, infanticide, and infant/child neglect.
      Reproductive technologies developed in the late 20th century allow determination
      of the sex of the offspring during pregnancy, making "sex selection" through
      abortion possible. Especially in parts of East and South Asia, sex selection
      against female fetuses has had dramatic consequences for male/female sex ratios.
      However, "newer" new reproductive technologies, such as prenatal genetic
      diagnosis and DNA-weighted semen selection, can now be applied for sex selection;
      eventually, the latter technology may become easily accessible as a noninvasive
      method. The prospects of these new technologies for sex selection must be
      considered in the light of cultural values surrounding son preference / daughter
      discrimination in many parts of the world, most notably Asia, as well as
      preferences for a "gender-balanced" family in much of the West. The ethical
      issues surrounding these technologies, such as the right to life and the equal
      treatment of female children, are potentially profound, but legislating the
      appropriate use of these "newest" new reproductive technologies will be
      difficult.

PMID- 12800887
TI  - Compensation for musculoskeletal disorders in Quebec: systemic discrimination
      against women workers?
AB  - Criteria for evaluating workers' compensation claims for occupational disease are
      strongly linked to medical expertise as supported by scientific study, yet
      decision-makers are not necessarily familiar with the meaning of these studies.
      While this is a problem for all claimants, who bear the burden of proving that
      work caused their injury, the adverse impact of misunderstanding of scientific
      data can have particular consequences for women, whose work more often appears to
      be benign. This article reports on a study of empirical data drawn from analysis
      of 314 workers' compensation appeal tribunal decisions on compensation claims, in
      Quebec, for musculoskeletal disorders alleged to be related to repetitive work.
      The study considers randomly selected decisions rendered between 1994 and 1996 on
      diagnoses of tendonitis, epicondylitis, and carpal tunnel syndrome and, in a
      follow-up, looks at significant legal decisions by the same tribunals, rendered
      over a longer period (1987-96). Results indicate that women workers are
      significantly less likely than their male counterparts to have their occupational
      disease claims accepted by the appeal tribunal. Evidence suggests that
      inappropriate overreliance on scientific studies for adjudication purposes
      contributes to a greater rate of refusal of claims by women workers.

PMID- 12800888
TI  - A second opinion: rethinking the public-private dichotomy for health insurance.
AB  - Does the public-private dichotomy effectively describe health insurance systems
      in the advanced industrialized democracies? Is the boundary separating the public
      and private sectors accurate for studies o f social policy formation and cutback?
      This article has three goals. The first is to discuss reasons for reconsidering
      the public-private dichotomy, as it applies to health insurance systems. The
      second is to offer a reconceptualization of the public-private demarcation useful
      for analyses of health insurance systems; the author presents four sectors that
      may illuminate patterns of health insurance for different OECD countries: the
      social, individual, public, and market sectors. The third goal is to present
      results using a new methodological approach useful for studying complex social
      phenomena: the fuzzy-set approach, which allows researchers to treat social
      phenomena as partially belonging to more than one category. This approach is
      employed to demonstrate that health insurance provision rarely is solely public
      or private, but is formed by a combination of sectors. Underlying these three
      goals is the contention that comparative and historical sociological researchers
      can offer innovative approaches to the study of health insurance and the
      interests served by public and nonpublic health insurance programs through
      reconceiving the public-private dichotomy.

PMID- 12800889
TI  - Myths as barriers to health care reform in the United States.
AB  - The U.S. health care system is deteriorating in terms of decreasing access,
      increased costs, unacceptable quality, and poor system performance compared with
      health care systems in many other industrialized Western countries. Reform
      efforts to establish universal insurance coverage have been defeated on five
      occasions over the last century, largely through successful opposition by pro
      market stakeholders in the status quo. Reform attempts have repeatedly been
      thwarted by myths perpetuated by stakeholders without regard for the public
      interest. Six myths are identified here and defused by evidence: (1) "Everyone
      gets care anyhow;" (2) "We don't ration care in the United States"; (3) "The free
      market can resolve our problems in health care"; (4) "The U.S. health care system
      is basically healthy, so incremental change will address its problems;" (5) "The
      United States has the best health care system in the world"; and (6) "National
      health insurance is so unfeasible for political reasons that it should not be
      given serious consideration as a policy alternative." Incremental changes of the
      existing health care system have failed to resolve its underlying problems.
      Pressure is building again for system reform, which may become more feasible if a
      national debate can be focused on the public interest without distortion by myths
      and disinformation fueled by defending stakeholders.

PMID- 12800891
TI  - State-based versus federal-based approaches to reducing the Medicare
      pharmaceutical coverage gap.
AB  - A state-based approach, such as the Immediate Helping Hand proposal put forward
      by the Bush administration, is likely to be less effective than a federal-based
      approach at reducing the Medicare pharmaceutical coverage gap. In addition, the
      voluntary nature of a state-based approach, coupled with variations across states
      in existing coverage benefits and the limited reach of state pharmacy assistance
      programs, would likely lead to a perpetuation of uneven coverage. This article
      argues in favor of adding a federal-based universal prescription drug benefit to
      Medicare on the grounds of both equity and empirical evidence. Adding a universal
      drug benefit to the currently existing Medicare program would extend application
      of the social insurance concept across hospital care, physician service, and
      prescription drug coverage components of Medicare. As a result, a more equitable
      distribution of prescription drug coverage would be promoted while mitigating the
      effects of selection risk.

PMID- 12800890
TI  - Prevalence and patterns of discrimination among U.S. health care consumers.
AB  - The authors examine the prevalence and patterns of perceived discrimination in
      the U.S. health care system and examine social status variables as determinants,
      using data from the Commonwealth Fund's Minority Health Survey. The primary
      social status groups of interest are age, race, ethnicity, social class, sex, and
      health status. Each social status category placed respondents at greater risk of
      perceiving discrimination based on the corresponding source of discrimination.
      That is, younger respondents were more likely to perceive age discrimination than
      were older respondents. African Americans and Hispanics perceived more race
      discrimination than whites. Low-income individuals experienced class
      discrimination, women experienced sex discrimination, and individuals who
      reported being in poor health were more likely to perceive discrimination based
      on health or disability status.

PMID- 12800892
TI  - The number of Americans without health insurance rose in 2001 and continued to
      rise in 2002.
AB  - Data from the Census Bureau and the Centers for Disease Control and Prevention
      indicate that the number of uninsured Americans rose in 2001and in the first
      quarter of 2002. The main reason insurance coverage fell was a drop-off in
      employer-sponsored insurance for workers and their dependents. This reduction was
      triggered by rising unemployment levels and rising health insurance premiums,
      which made it more difficult for employers to offer insurance or for workers to
      afford it. The downturn in private coverage was partially offset by increased
      enrollment in Medicaid and the State Children's Health Insurance Program (SCHIP).
      About two million mor e children and one million more adults would have been
      uninsured had it not been for the growth in these programs. Funding for the
      public programs is, however, threatened by budget shortfalls affecting most
      states, which administer these programs. Many states have cut their Medicaid
      programs and are planning further cutbacks. Increasing federal assistance to
      states and their Medicaid programs could help protect insurance coverage for low
      income people during the current economic slowdown. Future SCHIP enrollment could
      drop sharply because of a shortage of federal funds, and Congress could take
      steps to bolster SCHIP funding.

PMID- 12800893
TI  - OMB estimates indicate that 900,000 children will lose health insurance due to
      reductions in federal SCHIP funding.
AB  - Despite the success of the State Children's Health Insurance Program (SCHIP) in
      reducing the ranks of uninsured children, the program now faces significant
      financing challenges. Analysis based on a model developed by the Centers for
      Medicare and Medicaid Services indicates that by 2007, 20 states will have
      insufficient federal funding to sustain their current programs, with the first
      states affected in 2004. As a result, the Office of Management and Budget
      projected last year that SCHIP enrollment will fall by 900,000 children between
      2003 and 2007. The funding shortfalls are the result of several factors. Federal
      SCHIP funding fell by 26 percent--by more than dollar 1 billion-in each of fiscal
      years 2002, 2003, and 2004; dollar 1.2 billion in SCHIP funds has already expired
      and reverted to the Treasury at the end of fiscal year 2002, and another dollar
      1.5 billion will expire at the end of 2003. The SCHIP program also has a
      redistribution system with targeting and timing problems. However, proposed
      Congressional legislation restoring federal funding, extending the dollar 2.7
      billion in expiring funds, and targeting the funds to the states that most need
      them could avert most, if not all, of the projected enrollment decline. On the
      other hand, the Bush administration proposed to extend the expiring funds but
      does not target them to needy states; the proposal will do little to reduce the
      magnitude of the decline.

PMID- 12800894
TI  - Hype in health reporting: "checkbook science" buys distortion of medical news.
AB  - The greatest danger to public health might be "checkbook science": research
      intended not to expand knowledge or to benefit humanity but to sell products.
      Much of the media coverage of health news stories is based on public relations
      efforts on behalf of the companies that sell the products, including
      pharmaceutical companies, diet clinics, or doctors selling new techniques. The
      author presents three case studies of how companies selling medical products
      effectively but invisibly shaped recent news coverage of medical products: fen
      phen diet pills, breast implants, and hormone replacement therapy. All involve
      subtle strategies whereby physicians and other experts paid by corporate
      interests are influential because they are perceived to be objective medical
      experts. Articles in prestigious medical journals are sometimes ghostwritten by
      individuals paid by companies or are based on biased analyses or interpretations
      shaped by corporate interests. Nonprofit organizations that tout the benefits of
      specific medical products also may be part of the public relations efforts of the
      companies making the product. Meanwhile, important newsworthy studies are ignored
      by the mass media when corporate interests do not publicize or pitch the results
      to influential reporters and producers.

PMID- 12800895
TI  - Another health care system is possible.
AB  - A statement prepared by groups at the European Social Forum held in Florence in
      2002 declares health to be a fundamental and universal right, a right that is
      being denied by current neoliberal policies. The statement presents some
      essential principles for maintaining or restoring this right through a European
      network.

PMID- 12800896
TI  - Health for all or riches for some: WHO's responsible?
AB  - Can we still rely on the World Health Organization? It has not openly opposed the
      greed of the major global pharmaceutical companies, and its director-general, Gro
      Harlem Brundtland, has deferred to them.

PMID- 12800897
TI  - What are we thinking (you and I): Upchurch lecture.

PMID- 12800898
TI  - Plastic surgery: its roots and rewards.

PMID- 12800899
TI  - Clinical analysis of malar fat pad re-elevation.
AB  - Primary suture suspension of the malar fat pad has been described as a safe and
      simple component of global facial rejuvenation. This review evaluates the
      efficacy and indications for re-elevation of the malar fat pad elevation. A
      retrospective review of the medical records of patients who underwent malar fat
      pad elevation was performed between 1994 and 2000. Of 472 procedures, 14 involved
      re-elevation of the malar fat pad. These cases were examined for complications,
      risks, and results. Secondary midface elevation was performed using a
      subcutaneous approach to the malar fat pad through a pre-hairline incision and
      vertical suspension of the malar fat pad to the temporoparietal fascia. The
      indications for re-elevation of the malar fat pad included nasolabial asymmetry,
      malar fat pad malposition, and malar fat pad asymmetry. Primary elevation of the
      malar fat was performed in 472 patients. Fourteen of these patients had
      suboptimal results that necessitated re-elevation of their malar fat pads. Their
      average age was 57.5 years. Of the 14 malar fat pad elevations, 12 included SMAS
      procedures, nine were combined with platysmal plication/submental lipectomy, six
      with forehead lift, and three with eyelid procedures. The average interval
      between original malar fat pad elevation and the re-elevation was 40 months.
      Average follow-up was 15 months. Complications were seen in five patients, with
      the most significant being persistent eye irritation. Two patients had some
      minimal scar hypertrophy, which was self-limiting. Minor preauricular skin slough
      developed in one patient. Restoration of the youthful position of the deep
      structures in patients with a previous mid-facelift was successfully achieved by
      re-elevating the malar fat pad in a vertical direction. Re-elevation of the malar
      fat pad demonstrated effective and reliable long-term results. It is appropriate
      in the small number of patients who require revision or improvement of midface
      rejuvenation using the malar fat pad suspension technique.

PMID- 12800900
TI  - Skin-sparing mastectomy flap complications after breast reconstruction: review of
      incidence, management, and outcome.
AB  - This study assesses the incidence and outcome of skin-sparing mastectomy (SSM)
      flap complications after breast reconstruction. The authors performed a
      retrospective review of 37 consecutive patients undergoing SSM and immediate
      breast reconstruction, focusing on preoperative demographics, management of
      complications, and early outcome. Univariate analysis comparing patients with and
      without complications was performed using Student's t-test and chi-square
      analysis. From July 2000 to December 2001, 37 patients (mean age 48.1, range 24
      71 y) underwent SSM and breast reconstruction (unilateral 20, bilateral 17) via
      TRAM flaps (n = 18), latissimus flaps (n = 13), and expander/implants (n = 6).
      SSM flap complications occurred in nine patients (24.3%) and included mild (n =
      2), moderate (n = 5), and severe (n = 2) skin loss, resulting in four cases of
      dehiscence, five reoperations, and no delay in postoperative adjuvant therapy
      (required in six patients). Previous irradiation (n = 5, p = 0.045) and diabetes
      (n = 3, p = 0.001) were associated with SSM flap complications, but age, smoking,
      previous breast cancer, and type of reconstruction were not. Patients with SSM
      flap loss had a higher body mass index (BMI) than those without complications
      (30.0 vs. 24.3; p = 0.025). Skin flap complications after SSM and breast
      reconstruction are not uncommon but did not delay the initiation of adjuvant
      chemotherapy or radiotherapy, despite the need for reoperation. Patients with
      elevated BMI, diabetes, and previous irradiation may be at increased risk for SSM
      flap complications.

PMID- 12800901
TI  - Extended TRAM flap: feasibility study on fresh human cadavers.
AB  - The purpose of this study was to investigate the feasibility of a superiorly
      based TRAM flap for breast reconstruction with its superior border abutting the
      inframammary fold. This flap would have a primary blood supply from the superior
      epigastric vessels, similar to a free flap attached to the mammary system. This
      flap, however, would not require microsurgery. Instead, it would have its
      superior epigastric pedicle lengthened by partial rib resection. Donor site
      closure would be accomplished by reverse abdominoplasty and the donor scar hidden
      in the inframammary fold. The surgical anatomy of such an extended TRAM flap
      (eTRAM) was investigated by cannulation of the internal mammary artery (IMA) in
      10 fresh human cadavers bilaterally, injection with latex, and then dissection
      throughout its intrathoracic course. At the level of the third intercostal space,
      the mean external diameters of the right and left IMA were found to be 2.5 mm and
      2.3 mm, respectively. The diameter of the vessel decreased until the IMA
      bifurcated into the superior epigastric artery and the musculophrenic artery,
      usually at the sixth intercostal space. The superior epigastric artery, having a
      mean diameter of 1.6 mm at its origin, descended caudally behind the seventh
      costal cartilage and could be followed until it entered the posterior rectus
      sheath and the rectus abdominis muscle. On its downward course, it was not
      embedded in the diaphragm muscle and was easily separated without violation of
      the thoracic cavity. From this anatomic study, it seems to be possible to raise
      an eTRAM after partial rib resection. Some technical considerations of such a
      flap are discussed. This modification of the TRAM would be helpful to surgeons
      commonly performing pedicled TRAM flaps and might extend its applicability beyond
      breast reconstruction to chest wall, intrathoracic, and head and neck
      reconstruction.

PMID- 12800902
TI  - Role of connective tissue growth factor in breast implant elastomer capsular
      formation.
AB  - Transforming growth factor-beta (TGF-beta) has been demonstrated to be a mediator
      in scar formation and in multiple fibrotic disorders such as in Dupuytren
      contractures and in pulmonary fibrosis. Recently, it has been demonstrated that
      connective tissue growth factor (CTGF) is a downstream mediator of TGF-beta and
      acts to stimulate wound contraction and fibrosis. The purpose of this study is to
      assess the role of CTGF in the development of breast implant elastomer capsule
      formation over time and to evaluate the effects of TGF-beta and CTGF antisense
      (AS) oligonucleotides on capsule formation. Fifteen Sprague-Dawley rats were
      randomly assigned to treatment (n = 12) and control (n = 3) groups. Four 2- x 2
      cm pockets were created on the dorsum deep to the panniculus carnosus in each
      rat. A 1- x 1-cm smooth breast implant elastomer was placed. Each rat in the
      treatment group received 1 ml vehicle, AS-TGF-beta, AS-CTGF, or scramble
      antisense oligonucleotide (AS-scramble). Control rats received either 1 ml
      vehicle or 1 ml saline in each pocket. At weeks 1, 3, and 5, four treatment rats
      and one control rat were randomly selected and killed. Tissue blocks were
      harvested for determination of CTGF levels using the enzyme-linked immunosorbent
      assay technique and for hematoxylin and eosin slides to evaluate capsule
      formation. Levels of CTGF in capsular tissue treated with vehicle or AS-scrambled
      were similar and progressively increased in tissues on weeks 1, 3, and 5,
      compared with normal skin. At weeks 1 and 3 after surgery, levels of CTGF were
      suppressed in capsules treated with AS-CTGF or AS-TGF-beta compared with normal
      skin and with tissues treated with vehicle or AS-scramble (p = 0.002). At week 5,
      levels of CTGF were similar to levels in normal skin. Histological analysis
      revealed reduced capsular formation in samples treated with AS-CTGF or AS-TGF
      beta compared with the two other treated sites. In conclusion, a single and local
      treatment with AS-CTGF or AS-TGF-beta at the time of surgery reduced CTGF levels
      in tissue and correlated with reduced capsular formation in a rat model. These
      data suggest a new therapeutic strategy to reduce early capsular formation based
      on local application of antisense oligonucleotides targeting CTFG and TGF-beta.

PMID- 12800903
TI  - Successful closure of abdominal wall hernias using the components separation
      technique.
AB  - The "components separation" technique involves separating the layers of the
      abdominal wall to allow midline advancement. The purpose of the study was to
      compare the success rate of the components repair versus other methods. Repair
      methods included components separation (n = 11), mesh (n = 15), primary (n = 21),
      TFL grafts (n = 5), TFL or latissimus flaps (n = 4), and rectus turnover (n = 4).
      The results were: 16 of 60 hernias recurred, with significant risk factors being
      body mass index (BMI) greater than 30 kg/m2 (p = 0.04), wound infection or
      breakdown (p < 0.03), and possibly concurrent colostomy or enterocutaneous
      fistula repair (p = 0.11). Only one of 11 hernias recurred using the components
      methods, four of 15 recurred using mesh repairs, three of 21 recurred using
      primary repairs, four of five recurred using TFL grafts, two of four recurred
      using TFL/latissimus flaps, and two of four recurred using rectus turnovers.
      There were 19 complications (infection or wound breakdown), with risk factors
      being smoking (p = 0.002) and possibly BMI greater than 30 kg/m2 (p = 0.08). The
      results suggest that the components separation method is a viable option for
      repair of complex abdominal wall hernias without the use of distant flaps or
      grafts.

PMID- 12800904
TI  - Composite earlobe grafts to reconstruct the lateral nasal ala and sill.
AB  - Numerous operations have been described to address the unilateral cleft lip
      deformity. One area that has not received significant attention is the deficient
      join between the nasal ala and the upper lip. Several surgeons have advocated
      detaching the ala and rotating it medially to restore the nasal sill and decrease
      the alar flare. Unfortunately, many children with clefts do not have enough
      available tissue to perform these maneuvers without compromising the nostril
      opening. In this article, the authors present a technique using composite earlobe
      grafts with sandwiched cartilage grafts to restore symmetry with the
      contralateral nostril. This technique has also been used in adult patients
      undergoing reconstruction because of cancer ablation or traumatic injuries. All
      patients received adjuvant hyperbaric oxygen therapy.

PMID- 12800905
TI  - Anatomic basis of notch deformity in open rhinoplasty.
AB  - Notch deformity at the columella after the stairstep incision is an unsightly
      sequel that fuels negativism for open rhinoplasty critics. Obvious causes cited
      include surgical misadventures involving division of the foot of the medial crus
      and poor healing. The authors offer yet an additional etiology based on the
      contraction distortion caused by the depressor septi nasi muscle. The purpose of
      this study is to investigate the anatomic basis for notch deformity after
      stairstep technique in open rhinoplasty. For this anatomic study, 10 fresh
      cadavers were used. Dissections were performed, exposing the columellar
      components. The macroscopic and microscopic photo documentation gathered supports
      the authors' theory that depressor septi nasi action causes skin-edge deformation
      that leads to closure malalignment and notch deformity. Pre-incision landmark
      defining tattoo or sutures will assure proper alignment at closure.

PMID- 12800906
TI  - Reconstruction of through-and-through gunshot wounds to the feet with free
      gracilis muscle flaps.
AB  - Reconstruction of a through-and-through gunshot wound (GSW) to the foot remains a
      challenging problem for plastic and orthopedic surgeons, because it is difficult
      to achieve reliable soft tissue coverage of the foot while at the same time
      optimizing foot contour and weightbearing. In the past year, four patients with
      such an injury were treated with initial wound debridement and stabilization of
      the metatarsals, followed by a free gracilis muscle transfer with a split
      thickness skin graft. One patient also had a secondary iliac bone graft to the
      first metatarsal. All patients have completely healed wounds, are free of
      osteomyelitis, and have achieved an excellent contour and good ambulation of the
      foot without donor site problems. Thus, a free gracilis muscle transfer should be
      considered first for reconstruction of a through-and-through GSW to the foot,
      because it can provide reliable soft tissue coverage with excellent contour and
      minimal donor site morbidity.

PMID- 12800907
TI  - Use of orbicularis oculi muscle flap for undercorrected blepharoptosis with
      previous levator muscle resection.
AB  - Based on the detailed anatomy, the orbicularis oculi muscle and the orbital
      septum are the continuation of the frontalis muscle and its fascia. Therefore,
      the shortened orbicularis oculi muscle and orbital septum would transmit the
      frontalis muscle action more effectively. The superior-based orbicularis oculi
      muscle and orbital septum flap, as a single flap, were advanced and attached to
      the tarsal plate for the correction of blepharoptosis. Six patients with
      undercorrected blepharoptosis were included in this study. Each patient had
      undergone more than two levator resection procedures by ophthalmologists or
      plastic surgeons. Conventionally, the frontalis suspension procedure was the next
      choice in these cases. The shortened orbicularis oculi muscle and orbital septum
      flap was used in these cases. Postoperative results were satisfactory after 3
      year follow-up.

PMID- 12800908
TI  - Outcome of aspirin use during excision of cutaneous lesions.
AB  - The perioperative course of 253 patients undergoing excision of cutaneous and
      subcutaneous lesions by the same surgeon was evaluated, comparing patients using
      aspirin and those not using aspirin. Intraoperative methods of obtaining
      hemostasis and the incidence of postoperative complications were evaluated.
      Suture ligatures were used more frequently in the group using aspirin, but there
      was no statistical difference in the use of electrocautery. There was also no
      difference in the incidence of wound dehiscence, erythema, or hematoma. The
      outcome of excision of cutaneous and subcutaneous lesions under local anesthesia
      is not affected by patients using aspirin.

PMID- 12800909
TI  - Factors affecting composite graft survival in digital tip amputations.
AB  - Distal fingertip amputations present the hand surgeon with a myriad of treatment
      options. Composite tissue replantation offers the patient the possibility of
      maintaining digital length and function. The purpose of this study was to
      determine the efficacy of this treatment modality and to support its use. During
      a 2.5-year period, 53 patients with 57 digital tip amputations distal to the
      distal interphalangeal (DIP) joint underwent composite tissue grafting of the tip
      with minimal defatting. All patients were evaluated in a prospective manner.
      Specific information regarding the patient and the injury were recorded. The
      survival rates for amputations distal to the eponychium and between the DIP joint
      and eponychium were 58% and 43%, respectively. Smoking was the only significant
      factor that had a strong, independent association with graft loss. Age older than
      18 years and alcohol use appeared only initially to have an effect on graft
      survival because they were so closely linked with smoking. Diabetes mellitus and
      crush-type injuries may potentially predispose a graft to fail, but a larger
      sample size is needed to prove this with significance. There were no infections
      or serious complications, even in those grafts that failed. After reviewing the
      data, the authors recommend using composite tissue replantation for fingertip
      amputations distal to the DIP joint in nonsmokers.

PMID- 12800910
TI  - Use of suturing as a measure of technical competence.
AB  - There is an ongoing demand for surgeons to demonstrate that they can operate
      well, maintain their performance, and deliver acceptable results. Currently,
      surgeons are assessed by a series of subjective and peer-reviewed interviews, but
      at no stage is the objective assessment of surgical competence measured. The
      authors have introduced an objective test of suturing skill as one of an array of
      tests used to assess technical ability. A range of surgeons with differing
      surgical skill was tested. The candidates were asked to suture a 4-cm wound on a
      latex skin pad. They were videotaped during the procedure and were scored by four
      independent observers using the Objective Structured Assessment of Technical
      Skill scoring system. Their movements were also monitored using an
      electromagnetic tracking system. Forty-three plastic surgeons and 46 general
      surgeons were divided into four groups, depending on grade, and were assessed.
      The difference in scores among the plastic surgeons gave a value of p < 0.001,
      whereas the general surgeons gave a value of p = 0.001. However, when similar
      grade but different specialties were compared, plastic surgeons scored
      significantly higher (down to senior house officer [resident year 1-2] level;
      mean p value = 0.019). Interrater reliability was also high (Cronbach alpha =
      0.89). This task has shown that technical ability can be assessed objectively.
      The task has also been shown to exhibit face, construct, and concurrent validity.
      This has important implications for the future of surgical training in that it
      allows one to identify whether the fundamentals of surgical technique have been
      passed on to the trainee and to monitor their progress continually. It also may
      be used in revalidation of surgeons.

PMID- 12800911
TI  - Surgical correction of trismus in a child with Hecht syndrome.
AB  - Hecht syndrome is a rare condition that is also known as trismus
      pseudocamptodactyly syndrome. Short muscle and tendon units limiting the range of
      motion of upper and lower extremities and mouth characterize this disorder of
      muscle development. There is no consensus on the optimal treatment of
      temporomandibular joint (TMJ) ankylosis in this patient population. Endoscopic
      release in one patient resulted in early postoperative recurrence. The authors
      present a 28-month old boy who had a limited mouth opening of 6 mm. CT scan
      showed no bony ankylosis. The range of mouth opening did not to improve with
      physical therapy. The patient underwent extensive subperiosteal dissection of the
      mandible, bilateral coronoidectomy, and TMJ exploration. An intraoperative
      opening of 18 mm was achieved. The patient remained intubated until postoperative
      swelling resolved. He was extubated in the operating room 6 days later. The
      patient continued to improve with physical therapy. He had a 25-mm mouth opening
      at 12 months of follow-up.

PMID- 12800912
TI  - Simple approach to the radiated scalp wound using INTEGRA skin substitute.
AB  - The chronic irradiated scalp wound remains one of the most difficult
      reconstructions for the plastic surgeon. With its inherent radiodermatitis and
      poor healing potential, chronic ulcers down to bone will result if coverage
      cannot be achieved. Reconstructive procedures as simple as a skin graft have a
      high complication rate in the irradiated wound and often fail. Local tissue
      transfer also has a high failure and complication rate because of the decreased
      vascularity of the wound bed and radiation damage to the surrounding scalp
      tissue, limiting its manipulation. The authors report two cases using a simple
      method with INTEGRA bilaminate skin substitute (Integra Life Sciences,
      Plainsboro, NJ) for repair of difficult wounds of the radiated scalp. Case one
      involves a patient with nonhealing radiation ulcers that had failed local wound
      care, hyperbaric oxygen, and split-thickness skin grafting. Case two involves a
      patient with extensive squamous cell cancer of the scalp that recurred despite
      total scalp radiation, requiring resection of more than 50% of the total surface
      area of the scalp. Both these patients were successfully treated using INTEGRA
      artificial skin substitute (Integra Life Sciences). This simple method using
      INTEGRA (Integra Life Sciences) resulted in complete healing of the radiated
      scalp wound and an acceptable, functional, and cosmetic outcome with minimal
      morbidity to the patients.

PMID- 12800913
TI  - Reconstruction after total penile amputation and emasculation.
AB  - Amputation of the penis and testes is a rare injury in the pediatric population.
      The authors describe a case of traumatic amputation of the penis and testes
      presenting late for surgical reconstruction. The surgical reconstruction of this
      phallus involved advancement of the residual erectile tissue by division of the
      suspensory ligaments of the penis to lengthen the phallus. A glans penis was
      fashioned using a full-thickness skin graft with shaft skin provided by a split
      thickness skin graft. The use of a tissue expander allowed the creation of a
      scrotum that accepted two testicular prostheses. Reconstruction of the phallus
      using these techniques allowed the creation of an erectile, esthetically
      acceptable phallus. In the situation in which residual erectile tissue remains,
      this technique can be effectively used in place of musculocutaneous transfer
      flaps or gender reassignment.

PMID- 12800915
TI  - Facial atrophy in HIV-related fat redistribution syndrome: anatomic evaluation
      and surgical reconstruction.

PMID- 12800916
TI  - Turnover epineural sheath tube in primary repair of peripheral nerves.

PMID- 12800917
TI  - Systematic error in automated in-tube solid-phase microextraction.
AB  - The widely employed configuration for automated in-tube solid-phase
      microextraction (SPME) involves modification of a commercial liquid
      chromatographic autosampler into an automated extraction device. This popular
      configuration is demonstrated to result in an inherent systematic error in the
      quantitation of analyte in a given matrix. The source of error is traced to the
      accumulation of analyte in the extraction and the pre-extraction segment (i.e.,
      sample loop, metering valve and tubing prior to the metering valve) of the
      autosampler where the analyte comes in contact with the residual mobile phase.
      This results in cross-contamination due to sample/mobile phase mixing. The
      quantity of analyte accumulated in these segments is shown to consistently
      increase with the increasing number of draw/eject cycles. As a result of the
      accumulation, the amount of analyte recorded leads to inaccurate quantitative
      information, leading to overestimation of the limit of detection and limit of
      quantitation, when automated in-tube SPME is employed as an approach for sample
      enrichment. Insertion of a 100-microl air plug prior to extraction step was able
      to significantly minimize sample/mobile phase mixing of analyte with the residual
      mobile phase in the pre-extraction and extraction step, thus minimizing the
      systematic error.

PMID- 12800918
TI  - Optimisation of headspace solid-phase microextraction for the analysis of
      volatile phenols in wine.
AB  - Headspace solid-phase microextraction has been applied to the analysis of
      volatile phenols in wine. Silica fibre coated with Carbowax-divinylbenzene was
      found to be more efficient at extracting these compounds than other fibres such
      as those coated with polydimethylsiloxane, polyacrylate, carboxen
      polydimethylsiloxane, and polydimethylsiloxane-divinylbenzene. Different
      parameters such as extraction time, temperature of the sample during the
      extraction, ionic strength and sample volume were optimised using a two-level
      factorial design expanded further to a central composite design, in order to
      evaluate several possibly influential and/or interacting factors. The headspace
      (HS)-SPME procedure developed shows adequate detection and quantitation limits,
      and linear ranges for correctly analysing these compounds in wine. The recoveries
      obtained were close to 100%, with repeatability values lower than 16%. The method
      was applied to a variety of white and red wines.

PMID- 12800919
TI  - Trace analysis of sulfonylurea herbicides in water by on-line continuous flow
      liquid membrane extraction--C18 precolumn liquid chromatography with ultraviolet
      absorbance detection.
AB  - An on-line system that consists of continuous-flow liquid membrane extraction
      (CFLME), C18 precolumn, and liquid chromatography with UV detection was applied
      to trace analysis of sulfonylurea herbicides in water. During preconcentration by
      CFLME, five target compounds, including metsulfuron methyl, bensulfuron methyl,
      tribenuron methyl, sulfometuron methyl, and ethametsulfuron, were enriched in 960
      microl of 0.5 mol l(-1) Na2CO3-NaHCO3 (pH 10.8) buffer used as acceptor. This
      acceptor was on-line neutralized and transported to the C18 precolumn where the
      analytes were absorbed and focused. Then the focused analytes were injected onto
      a C18 analytical column for separation and detection at 240 nm. The proposed
      method was applied to determine sulfonylurea herbicides in water, river, and
      reservoir water with detection limits of 10-50 ng l(-1) when enriching a 120-ml
      sample. Throughput is typically one sample per hour.

PMID- 12800920
TI  - Analysis of food colorants by capillary electrophoresis with large-volume sample
      stacking.
AB  - A technique combining an on-capillary concentration method known as large-volume
      sample stacking and high-efficiency CE separation has been developed to analyze
      and detect colorants in several food samples, such as soft drinks, jellies and
      milk beverages. Following optimization, this technique significantly reduced the
      limits of detection of eight food colorants commonly used in food products by up
      to two orders of magnitude when compared with the conventional capillary
      electrophoresis method. The developed technique was able to successfully
      determine colorants in food samples that had concentrations as low as 0.1-0.5
      microg/ml.

PMID- 12800921
TI  - Effect of the mobile phase composition on the isotherm parameters and the high
      concentration band profiles in reversed-phase liquid chromatography.
AB  - Single-component adsorption isotherm data were acquired by frontal analysis for
      phenol on a C18-Kromasil packed column, under reversed-phase liquid
      chromatography conditions, using various methanol-water solutions (30-60%, v/v,
      methanol). The isotherm model accounting best for these data was the biLangmuir
      model. With increasing methanol content, the two saturation capacities decrease,
      particularly that of the high-energy sites, the adsorption constant of the low
      energy sites decreases significantly and that of the high-energy sites decreases
      strongly. These results allow a quantitative investigation of the properties of
      the high-energy sites (which are not necessarily the so-called active sites), a
      feature rarely discussed yet. The band profiles calculated with the numerical
      values of the isotherm model parameters derived by fitting the frontal analysis
      data to the model and using the equilibrium-dispersive model agree very well with
      the experimental band profiles in the whole concentration range.

PMID- 12800922
TI  - pH dependence of the hydrophobicity of beta-blocker amine compounds measured by
      counter-current chromatography.
AB  - The octanol-water partition coefficients (Poct) of 17 antiadrenergic beta-blocker
      compounds were determined by counter-current chromatography (CCC). Since CCC uses
      a biphasic liquid system, the octanol-water liquid system was used with
      essentially an octanol stationary phase and aqueous buffer mobile phase. The Poct
      coefficients were obtained directly without any extrapolation. The measured Poct
      values were in the 0.0015-4070 range (-2.8 < log Poct < 3.6). Since the beta
      blocking agents are ionizable compounds, the Poct values obtained were strongly
      dependent on the aqueous-phase pH. The apparent Poct coefficients of the beta
      blockers were determined at three different pH values (approximately 3, 7 and 11)
      using 0.01 M ammonium phosphate buffers saturated with octanol. A model allowed
      us to obtain the molecular and ionic Poct value using the solute pKa with these
      three experimental octanol-water coefficients. Often, the Poct coefficients of
      the molecular forms obtained with the CCC method differ significantly from
      computed literature values and/or experimental values obtained by extrapolation.
      Relationships between biological properties and hydrophobicity were also
      examined.

PMID- 12800923
TI  - Kinetic analysis and subambient temperature on-line on-column derivatization of
      an active aldehyde.
AB  - The chromatographic analysis of aldehydes under typical reversed-phase conditions
      may be a challenging task due to an equilibrium process leading to the formation
      of a gem diol species regardless of acidic or basic conditions. Initially, a
      reversed-phase HPLC gradient elution was developed to determine the amount of a n
      acetylenic aldehyde in a reaction mixture. Significant fronting was observed
      under acidic and basic conditions even at -5 degrees C. In order to circumvent
      this problem, a reversed-phase HPLC gradient method on a C18 column at subambient
      temperature was developed using diethylamine as a mobile phase additive for on
      line on-column derivatization of the aldehyde moiety. The on-line on-column
      reaction rate for the derivatization of the aldehyde with diethylamine was
      determined as a function of column temperature. An Arrhenius plot was constructed
      and the activation energy was calculated. The chromatographic behavior of the
      derivatized acetylenic aldehyde and products formed in-situ in the
      chromatographic system were studied at various temperatures ranging from -10 to
      60 degrees C. It was found that the reaction products could be controlled by
      adjusting the column temperature. Different reaction pathways were identified as
      a function of temperature. The products and the reaction pathways were
      characterized by NMR, LC-MS and UV spectra.

PMID- 12800924
TI  - True or apparent reversal of elution order during chiral high-performance liquid
      chromatography monitored by a polarimetric detector under different mobile phase
      conditions.
AB  - The use of all chromatographic modes (i.e. reversed-phase, normal-phase and polar
      organic modes) is becoming more and more systematic in chiral HPLC method
      development. When this method development is monitored by polarimetric detection,
      which is a widespread technique, one should not forget that the observed positive
      or negative rotation angle for a given absolute configuration depends on the
      solvent. As a cautionary illustration, a new example is reported for a racemate
      which is separated with the same elution order in ethanol or acetonitrile mobile
      phase on a CHIRALCEL OD-R column whereas the signs of polarimetric detection are
      reversed.

PMID- 12800925
TI  - Optimization, validation and comparison of various extraction techniques for the
      trace determination of polycyclic aromatic hydrocarbons in sewage sludges by
      liquid chromatography coupled to diode-array and fluorescence detection.
AB  - There is a need for a better characterization of sludges from wastewater
      treatment plants which are destined to be spread on agricultural lands. Inorganic
      pollutants are regularly controlled but organic pollutants have received few
      attention up to now. On this paper, we have been interested on the analysis of
      the 16 polycyclic aromatic hydrocarbons (PAHs) listed in the US Environmental
      Protection Agency (US EPA) priority list and more particularly of the six PAHs
      listed in the European community list (fluoranthene, benzo[b and k]fluoranthene,
      benzo[a]pyrene, benzo[ghi]perylene, indeno[1,2,3-cd]pyrene). The analysis step
      consists on liquid chromatography with both fluorescence and UV detections as
      described in the EPA Method 8310. As for the extraction step, several techniques
      such as supercritical fluid extraction, pressurized liquid extraction, focused
      microwave extraction in open vessels, Soxhlet and ultrasonic extractions are
      compared after optimization of the experimental conditions (solvent nature and
      quantity, temperature, pressure, duration, ... ) and validation with certified
      sludges. When optimized, these five extraction techniques are as much efficient
      with similar relative standard deviation. Whatever the extraction techniques
      used, the whole analysis protocol permits to quantify PAHs in the range of 0.09
      to 0.9 mg/kg of dried sludges.

PMID- 12800926
TI  - Analysis of proanthocyanidins by high-performance gel permeation chromatography.
AB  - A high-performance gel permeation chromatography method was developed for the
      analysis of proanthocyanidins. The isocratic method consisted of two porous
      polystyrene-divinylbenzene columns (300 x 7.5 mm each, 5 microm, 100 and 500 A
      individual pore size) and a mobile phase consisting of N,N-dimethylformamide
      containing 1% (v/v) acetic acid, 5% (v/v) water and 0.15 M lithium chloride. The
      flow-rate was maintained at 1 ml/min, with a column temperature of 60 degrees C
      and with detection at 280 nm. The method was used to analyze proanthocyanidin
      fractions of increasing molecular mass and from different plant tissues. The
      average molecular mass of proanthocyanidin fractions as determined by acid
      catalysis in the presence of phloroglucinol, related well with their gel
      permeation chromatography column retention, yet significant differences in the
      retention properties between individual plant tissue isolates existed.
      Proanthocyanidin compositional differences between isolates may explain these
      differences. A second-order calibration curve was generated from fractionated
      grape seed proanthocyanidins and this curve was used to analyze grape seed
      proanthocyanidins isolated from grapes harvested at extremes of maturity.

PMID- 12800927
TI  - Identification of acylated xanthone glycosides by liquid chromatography
      atmospheric pressure chemical ionization mass spectrometry in positive and
      negative modes from the lichen Umbilicaria proboscidea.
AB  - The xanthoside composition of the crude extract of Umbilicaria proboscidea (L.)
      Schrader was characterized using LC-UV diode array detection and LC-atmospheric
      pressure chemical ionization (APCI) MS methods. The presence of acylated xanthone
      O-glucosides was determined by both positive and negative ion LC-APCI-MS methods.
      Based on UV and MS spectral data and NMR spectroscopy, a total of 14 compounds (6
      O-acylated umbilicaxanthosides A and B) were identified in U. proboscidea for the
      first time. In order to further develop the applicability of LC-MS techniques in
      phytochemical characterization, the effect of different ionization energy on
      fragmentation was studied using APCI. The optimal ionization conditions were
      achieved in positive ion APCI by using ammonium acetate buffer and in negative
      ion APCI by using formic acid (pH 4).

PMID- 12800928
TI  - Quantitative determination of phenolic diterpenes in rosemary extracts. Aspects
      of accurate quantification.
AB  - Practical challenges related to accurate quantification of carnosic acid (CA),
      carnosol (CAR) and other phenolic diterpenes in extracts of rosemary leaves
      (Rosmarinus officinalis L.) are presented and discussed. Primary standard
      material of CA is isolated from rosemary extracts by preparative chromatography
      with a purity of 98% or higher. The response factors of CAR relative to CA, at
      230 and 280 nm, have been estimated to be 0.92 and 1.36, respectively. The
      stability of pure CA and CAR, dissolved in methanol, dimethyl sulfoxide (DMSO),
      DMSO-acetonitrile (10:90) or ethyl acetate-acetonitrile (10:90) and stored at
      room temperature in the autosampler, is presented. Pure CA dissolved in DMSO is
      stable for several days, while CAR showed significant degradation within a few
      hours in all solvents tested. The lack of stability of standards results in
      practical difficulties with calculating reliable response factors. A correction
      procedure is presented and documented. A CAR calibration solution was analysed
      six times for purity during 30 h of storage, while the purity changed from 95 to
      70%. Applying this correction procedure resulted in a relative standard deviation
      on the average response factor of 0.7% (n=6). CA has been dissolved in methanol
      and stored in clear and amber glass vials, respectively. The solution stored in
      amber vials degraded faster that in clear vials. The high content of Ti and Fe
      ions in amber glass seems to catalyse the degradation of CA. In contrast to
      solutions of pure CAR and CA, their stabilities in solutions of rosemary extracts
      are fine. A standard addition experiment, covering a time interval of 21 h,
      resulted in recoveries of CAR and CA of 100 and 96%, respectively.

PMID- 12800929
TI  - Separation of enzymes by sequential macroaffinity ligand-facilitated three-phase
      partitioning.
AB  - Pectinase and cellulase were separated from a commercial enzyme preparation
      called Pectinex Ultra SP-L. This was carried out using a process called
      macroaffinity ligand-facilitated three-phase partitioning (MLFTPP). In this
      method, a water-soluble polymer is floated as an interfacial precipitate by
      adding ammonium sulfate and tert.-butanol. The polymer (appropriately chosen) in
      the presence of an enzyme for which it shows affinity, selectively binds to the
      enzyme and floats as a polymer-enzyme complex. In the first step, pectinase was
      purified (with alginate as the polymer) 13-fold with 96% activity recovery. In
      the second MLFTPP step, using chitosan, cellulase was purified 16-fold with 92%
      activity recovery. Both preparations showed a single band on sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. This illustrative example
      shows that the strategy of sequential MLFTPP can be used to separate important
      biological activities from a crude broth.

PMID- 12800930
TI  - Coupling solid-phase microextraction and high-performance liquid chromatography
      for direct and sensitive determination of halogenated fungicides in wine.
AB  - A solid-phase microextraction (SPME) method coupled to high-performance liquid
      chromatography with diode array detection (HPLC-DAD) for the analysis of six
      organochlorine fungicides (nuarimol, triadimenol, triadimefon, folpet,
      vinclozolin and penconazole) in wine was developed. For this purpose,
      polydimethylsiloxane-divinylbenzene-coated fibers were utilized and all factors
      affecting throughput, precision, and accuracy of the SPME method were
      investigated and optimized. These factors include: matrix influence, extraction
      and desorption time, percentage of ethanol, pH, salt effect and desorption mode.
      The performed analytical procedure showed detectability ranging from 4 to 27
      microg l(-1) and precision from 2.4 to 14.2% (as intra-day relative standard
      deviation, RSD) and 4.7-25.7% (as inter-day RSD) depending on the fungicide. The
      results demonstrate the suitability of the SPME-HPLC-DAD method to analyze these
      organochlorine fungicides in red wine.

PMID- 12800931
TI  - Determination of sodium at low ng/l concentrations in simulated power plant
      waters by ion chromatography.
AB  - The determination of low ng/l sodium in the power industry is critical in
      identifying and preventing corrosive conditions in many power plant components.
      To address this challenge, we developed an ion chromatographic method to
      determine sodium at ng/l concentrations in power plant samples. The ion
      chromatography system used on-line electrolytic eluent generation with a
      continuously regenerated trap column to minimize system contaminants and
      therefore allow low detection limits. A 10-ml sample was preconcentrated on a
      cation-exchange column followed by separation on a high capacity column with 20
      mM methanesulfonic acid and detected using suppressed conductivity. Sodium
      response was linear from 25 to 250 ng/l (r2=0.9990). Method performance was
      evaluated by analyzing synthetic samples containing ethanolamine as an additive
      that are typical of samples encountered in the power industry. Retention time
      precision for sodium was less than 0.4% (n=7) in ultrapure water and simulated
      sample matrices. The recovery of sodium spiked in synthetic samples at the low
      ng/l levels was 85-110%. System parameters were optimized to achieve method
      detection limits in ultrapure water to 3.2 ng/l.

PMID- 12800932
TI  - Simultaneous separation of inorganic anions and cations by using anion-exchange
      and cation-exchange columns connected in tandem in ion chromatography.
AB  - Inorganic anions and cations in environmental waters were determined by ion
      chromatography. Stationary and mobile phases were examined for the simultaneous
      separation of both anions and cations. Cations detection by UV detection requires
      a mobile phase with a UV absorbing additive, which indirectly visualizes cations
      as negative peaks. Simultaneous separation of anions and cations were achieved
      when using an eluent that consists of inorganic acid with weak basic amino acid
      as additives. It was convenient to separate both anions and cations by coupling
      anion-exchange and cation-exchange columns in tandem. The order of the separation
      columns connected affected the elution profiles. When the eluent comprises of
      multiple anions and a single cation, the anion-exchange column should be
      connected in the upper stream, whereas when the eluent comprises multiple cations
      and a single anion, the cation-exchange column should be connected in the upper
      stream. Use of switching valves also allowed simultaneous separation of anions
      and cations in a single chromatographic run. In the present work, operating
      conditions were optimized for the simultaneous separation of anions and cations.

PMID- 12800933
TI  - Different multidimensional chromatographic approaches applied to the study of
      wine malolactic fermentation.
AB  - Different multidimensional chromatographic techniques were used to study wine
      aroma pattern changes during malolactic fermentation (MLF). Ethyl lactate
      enantiomeric ratios were determined using on-line multidimensional gas
      chromatography. The values found agree with a spontaneous MLF. Off-line
      multidimensional HPLC/GC was used to deconvolute and enrich the sample and ease
      enantioselective chromatography. Chiral compound enantiomeric ratio changes
      during MLF were monitored. Evaluation of enantiomeric ratio changes during MLF
      has never been studied. (R,R), (S,S) and meso-butane-2,3-diol and pentane-2,4
      diol (reported in wines for the first time) were submitted to untrained sensory
      panel tests. All stereoisomers revealed different sensory notes; pentane-2,4-diol
      showed an aromatic impact.

PMID- 12800934
TI  - Simultaneous determination of methyl tert.-butyl ether and its degradation
      products, other gasoline oxygenates and benzene, toluene, ethylbenzene and
      xylenes in Catalonian groundwater by purge-and-trap-gas chromatography-mass
      spectrometry.
AB  - In Catalonia (northeast Spain), a monitoring program was carried out to determine
      methyl tert.-butyl ether (MTBE), its main degradation products, tert.-butyl
      alcohol (TBA), tert.-butyl formate (TBF), and other gasoline additives, the
      oxygenate dialkyl ethers ethyl tert.-butyl ether, tert.-amyl methyl ether and
      diisopropyl ether and the aromatic compounds benzene, toluene, ethylbenzene and
      xylene (BTEX) in 21 groundwater wells that were located near different gasoline
      point sources (a gasoline spill and underground storage tank leakage). Purge-and
      trap coupled to gas chromatography-mass spectrometry was optimised for the
      simultaneous determination of the above mentioned compounds and enabled to detect
      concentrations at ng/l or sub-microg/l concentrations. Special attention was
      given to the determination of polar MTBE degradation products, TBA and TBF, since
      not much data on method performance and environmental levels are given on these
      compounds in groundwater. All samples analysed contained MTBE at levels between
      0.3 and 70 microg/l. Seven contaminated hot spots were identified with levels up
      to US Environmental Protection Agency drinking water advisory (20-40 microg/l)
      and a maximum concentration of 670 microg/l (doubling the Danish suggested
      toxicity level of 350 microg/l). Samples with high levels of MTBE contained 0.1
      60 microg/l of TBA, indicating (but not proving) in situ degradation of parent
      compound. In all cases, BTEX was at low concentrations or not detected showing
      less solubility and persistence than MTBE. This fact confirms the suitability of
      MTBE as a tracer or indicator of long-term gasoline contamination than the
      historically used BTEX.

PMID- 12800935
TI  - Description and characterization of an on-line system for long-term measurements
      of isoprene, methyl vinyl ketone, and methacrolein in ambient air.
AB  - In this work we present a detailed technical description of the system that was
      set up for long-term on-line measurements of isoprene and two of its major
      degradation products, methyl vinyl ketone and methacrolein in order to provide a
      better understanding of the role of forest stands as a complex source of reactive
      trace gases into the troposphere and to elucidate the role of forests as chemical
      reactors. Volatile organic compounds (VOCs) are preconcentrated on cartridges
      containing a package of two solid adsorbents (Tenax TA and Carbopack X). Ozone
      removal is performed prior to sampling by titration with nitrogen monoxide. For
      the calibration and characterization of the system, a diffusion source was built
      to produce standard gas mixtures of up to 16 different compounds with mixing
      ratios at tens ppt (parts per trillion) level mixing ratios and high accuracy.
      The developed system allows a reliable quantification of these VOCs (detection
      limit approximately 10 ppt, reproducibility approximately 5%) with a high
      temporal resolution (approximately 30 min) and has proven to be stable and run
      automatically without major maintainence.

PMID- 12800936
TI  - Analysis of long-chain polyprenols using supercritical fluid chromatography and
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - The separation of long-chain polyprenols was successfully achieved using
      supercritical fluid chromatography (SFC). Each 100-mer greater component was
      separated using tetrahydrofuran as a mobile phase modifier. The molecular mass
      distributions derived from SFC analyses agreed with the results of matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) analyses. The number-average molecular mass calculated by MALDI-TOF-MS data
      were also in accord with the results of quantitative 1H-NMR analysis of terminal
      groups. A combination of SFC and MALDI-TOF-MS analyses is a powerful tool for the
      elucidation of the complicated structures of natural polyprenols.

PMID- 12800937
TI  - Behavior of neutral solutes in pressurized flow driven electrochromatography
      using a mixed stationary phase of ODS and anion-exchange.
AB  - The behavior of neutral sample solutes in pressurized flow driven
      electrochromatography using a mixed stationary phase, which consisted of ODS and
      anion-exchange (ODS-SAX), was studied. Applications of both positive and negative
      voltage on a column induced increases in retention factors of sample solutes. The
      direction of an electroosmotic flow under applications of positive and negative
      voltage were the same, therefore, the sign of the surface charge density under
      positive and negative voltage was opposite. We proposed a new equation for the
      relationship between applied voltage and surface charge density, and the
      practical electroosmotic flow conformed to this equation. Studying the
      electroosmotic flow using our proposed equation revealed that the applied
      negative voltage accelerates the protonation of the quaternary ammonium group and
      dissociation of the silanol group on packing materials. The retention behavior of
      a neutral solute was affected by the existence of the charged functional groups.
      We propose that this phenomenon is applicable to the control of the retention
      behavior of a sample solute using an electric field.

PMID- 12800938
TI  - Modification and validation of the pyromellitic acid electrolyte for the
      capillary electrophoretic determination of anions.
AB  - For the determination of inorganic and organic anions, the pyromellitic acid
      (PMA) electrolyte is widely used. The pH adjustment of the self-prepared
      electrolyte was very challenging to satisfy the pH of specification of pH 7.8 +/-
      0.1. A modification was proposed to provide a more simple electrolyte by
      buffering the PMA electrolyte with triethanolamine (TEA) only instead of
      adjusting the pH by NaOH and TEA. Thus, the proposed electrolyte consisted of
      2.25 mmol l(-1) PMA, 0.75 mmol 1(-1) hexamethonium hydroxide and 12 mmol 1(-1)
      TEA. The performance of the PMA electrolyte buffered by TEA only was compared to
      a commercial available PMA and statistically validated in accordance with the
      methodology of Taguchi. No statistically significant difference could be found
      for both electrolytes assessing the performance and detection limits of
      hydrodynamic, stacking and electrokinetic injection with transient
      isotachophoretic preconcentration as well as repeatability of migration times,
      peak resolutions and peak symmetries.

PMID- 12800939
TI  - Feasibility of supercritical fluid extraction with on-line coupling of reversed
      phase liquid chromatography for quantitative analysis of polymer additives.
AB  - An on-line analytical method for determining polymer additives which incorporates
      (a) sample preparation and concentration, (b) chromatographic separation, and (c)
      UV detection is presented. The on-line system which combines supercritical fluid
      extraction (SFE) and high-performance liquid chromatography (LC) allows analytes
      to first be extracted and transferred to the SFE sorbent trap, then desorbed from
      the trap and presented to the LC system. No UV detector interference from
      residual dissolved CO2 in the mobile phase was observed since CO2 is eliminated
      by a pre-wash of the sorbent trap with a small amount of water. Reversed-phase LC
      with a mobile phase gradient of acetonitrile-water was employed. The described
      method allows a complete analysis to be processed in less than 30 min.

PMID- 12800940
TI  - On-line solid-phase extraction with molecularly imprinted polymers to selectively
      extract substituted 4-chlorophenols and 4-nitrophenol from water.
AB  - Three polymers have been synthesised using 4-chlorophenol (4-CP) as the template,
      following different protocols (non-covalent and semi-covalent) and using
      different functional co-monomers, 4-vinylpyridine (4-VP) and methacrylic acid
      (MAA). The polymers were evaluated to check their selectivity as molecularly
      imprinted polymers (MIPs) in solid-phase extraction (SPE) coupled on-line to
      liquid chromatography. The solid-phase extraction procedure using MIPs (MISPE),
      including the clean-up step to remove any interferences, was optimised. The 4-VP
      non-covalent polymer was the only one which showed a clear imprint effect. This
      MIP also showed cross-reactivity for the 4-chloro-substituted phenols and for 4
      nitrophenol (4-NP) from a mixture containing the 11 priority EPA (Environmental
      Protection Agency) phenolic compounds and 4-chlorophenol. The MIP was applied to
      selectively extract the 4-chloro-substituted compounds and 4-NP from river water
      samples.

PMID- 12800941
TI  - Determination of aromatic amine mutagens, PBTA-1 and PBTA-2, in river water by
      solid-phase extraction followed by liquid chromatography-tandem mass
      spectrometry.
AB  - We describe a novel method for the determination of two kinds of aromatic amine
      mutagens, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)-amino]-5-amino-7-bromo-4
      chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[bis(2-cyanoethyl)
      ethylamino]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), in river water
      based on liquid chromatography-electrospray ionization-tandem mass spectrometry
      (LC-ESI-MS-MS). A solid-phase extraction procedure was used for the extraction of
      PBTA-1 and PBTA-2 from river water. The procedure was rapid and the relative
      standard deviations were below 4%. The detection limits of PBTA-1 and PBTA-2 in
      river water using the proposed method were found to be 1 and 2 ng/l,
      respectively. The compounds were detected by this method in river water taken
      from two sites in the Yodo River system at the ng/l level.

PMID- 12800942
TI  - A polymorphic CA repeat in the promoter region of the insulin-like growth factor
      I (IGF-I) gene.

PMID- 12800943
TI  - Comparison of early and delayed respondents to a postal health survey: a
      questionnaire study of personality traits and neuropsychological symptoms.
AB  - Delayed response to a mail survey is related to age, lifestyle and socioeconomic
      status, and may provoke bias in epidemiological study. We investigated whether
      delayed respondents were associated with their personality traits and
      neuropsychological symptoms. Two hundred and ninety-eight painters from a
      Scottish dockyard cohort and their 571 male controls (general subjects) randomly
      recruited from the local residents completed a questionnaire, which included 24
      statements of the Eysenck personality scales and 22 questions of
      neuropsychological symptoms. There was a similar distribution of delayed response
      between general subjects and painters, with a total of 55.6% early (returning
      questionnaires within 4 weeks), 33.4% intermediate (within 8 weeks) and 11.0%
      late respondents (after 8 weeks). The delayed response was related to only a few
      individual statements or symptoms, which varied between general subjects and
      painters. There were no significant differences in scores in statements of
      personality traits and neuropsychological symptoms among the three respondent
      groups, except for the late respondents in painters having an increased score of
      total neuropsychological symptoms at borderline significance. After adjustment
      for confounding the case-control analysis showed no significant association of
      the high scores of social conformity, neuroticism and symptoms with a delayed
      response. This study suggests that response to a postal health survey may not be
      influenced or biased by personality traits and neuropsychological symptoms.

PMID- 12800944
TI  - Genotype-phenotype analysis for the polymorphic CA repeat in the insulin-like
      growth factor-I (IGF-I) gene.
AB  - Polymorphic microsatellite dinucleotide (cytosine-adenine, CA) repeats of the
      insulin-like growth factor-I (IGF-I) gene may have implications in the
      development of certain types of cancer and osteoporosis. We studied correlations
      between IGF-I genotypes determined by direct sequencing and plasma IGF-I levels
      among 113 healthy individuals (60 men and 53 women), who were originally enrolled
      as controls for hospital-based case-control studies of breast and prostate
      cancer. On the contrary to an earlier observation, there were no differences in
      plasma IGF-I levels between those with and without the allele of 19 repeats. With
      adjustment for other confounders, there were no trends in plasma IGF-I levels
      with increasing or decreasing the number of CA repeats among all study subjects
      combined, all Whites or all Blacks, suggesting no overall functional significance
      of this polymorphism. Opposite trends observed in gender and racial subgroups,
      i.e., an inverse association between plasma IGF-I levels and the CA repeat length
      in white women and a positive association in black men, are likely to be chance
      findings.

PMID- 12800945
TI  - Epidemiology of essential hypertension: the role of genetic polymorphism.
AB  - Over the past 20 years, the interest of the scientific community was increasingly
      placed in the field of genetic epidemiology and molecular genetics of blood
      pressure control. This paper explores references related to essential
      hypertension, gene and genetic epidemiology indexed in the MedLine health science
      database during the period 1980-2001. A systematic literature search was
      performed using selected keywords, such as 'genetic', 'genome' or a combination
      of words. We considered the study heading and evaluated the time profile of
      published articles. A total number of 3116 publications was collected and
      analyzed. Allelic distribution for the most studied polymorphisms of the renin
      angiotensin system in different world populations was reviewed and reported
      together with a detection of their frequency in Italy: essential hypertensive
      patients (n = 90), healthy unrelated subjects (n = 300). Molecular variants at
      angiotensinogen (M and T), angiotensin II type 1 receptor (A and C) and
      angiotensin-converting enzyme (D and I) genes were analyzed by amplified fragment
      length polymorphism. A significant association was detected by chi2 analysis for
      angiotensinogen and angiotensin II-type I receptor allele distribution in
      hypertensive patients, in accordance with previous reports. Genetic data and
      methods are contributing more and more to epidemiological studies of complex
      diseases, and their application is influenced by information availability and
      Genome Project results.

PMID- 12800946
TI  - Familial resemblance of adiposity-related parameters: results from a health check
      up population in Taiwan.
AB  - The mechanisms of obesity is still unclear, however, genetic and environmental
      factors are two major possible causes of obesity. The purpose of this study was
      to assess the degree of familial resemblance of different obesity-related
      parameters in a health check-up population in Taiwan. We measured body mass index
      (BMI), waist-to-hip ratio (WHR) and percentage of body fat (BFAT) anthropometrics
      in 1724 members of 431 families participating in the MJ Health Screening program.
      Each family contributed four members, i.e. father, mother, son, and daughter. All
      the participants were free from coronary heart disease, hypertension, diabetes,
      dyslipidemia, and generally in good health. The degree of familial aggregation
      was measured by heritability that was calculated based on age-adjusted familial
      (parent-offspring, sibling, spouse) correlations. The maximal heritability
      estimates were 39, 30 and 35% for BMI, WHR and BFAT, respectively. For WHR, the
      correlation between spouses was not significant and the heritability appears to
      be predominantly due to genetic causes. Furthermore, for BMI and BFAT, the spouse
      correlations were 0.08 and 0.11, respectively. The heritabilities for BMI and
      BFAT were mostly explained by genetic factors and familial environmental factors
      such as dietary habits or physical activity. The familial resemblance of various
      obesity-related parameters was moderate in a health check-up population in
      Taiwan. While the heritability for WHR appears to be mainly due to genetic
      factors, the familial resemblance for BMI and percentage of BFAT may involve both
      genetic and familial environmental factors.

PMID- 12800947
TI  - The contribution of lifestyle factors to socioeconomic differences in obesity in
      men and women--a population-based study in Sweden.
AB  - BACKGROUND: The objective was to investigate whether and to what extent the
      association between socioeconomic status and obesity can be explained by
      lifestyle factors. METHODS: The relationship between socioeconomic status (SES)
      and obesity, and the role of lifestyle factors such as smoking, physical
      activity, heavy alcohol use, avoidance of dietary fat and propensity to eat fiber
      rich food, was studied in a cross-sectional population-based study consisting of
      6394 men and women aged 25-74 years in Varmland County in Sweden. Educational
      level was used for measuring SES. The contribution of the measured lifestyle
      factors was assessed using logistic regression models. RESULTS: 12% of men and
      14% of women were obese. Subjects with high education were leaner than subjects
      with low education, except among elderly women (65-74 years). Although many
      lifestyle factors were related to obesity and SES in this study, only a part (18
      29%) of the association between educational level and obesity could be explained
      by the measured lifestyle factors. Physical inactivity and heavy alcohol use were
      the main factors contributing to this association, whereas smoking and the
      measured dietary attitudes towards fat and fiber had little additional effect.
      CONCLUSIONS: The findings of this study are consistent with the view that
      socioeconomic differences in obesity and its consequences can only partly be
      reduced by changes in lifestyle. Longitudinal studies, a more detailed
      investigation of the role of dietary factors and more studies including elderly
      subjects are, however, recommended to further elucidate the association between
      SES and obesity.

PMID- 12800948
TI  - Risk factors for low birth weight in a socio-economically disadvantaged
      population: parity, marital status, ethnicity and cigarette smoking.
AB  - Low birth weight (LBW) is a public health problem, because it is associated with
      increased risk of morbidity and mortality. The principal aim of this study was to
      assess risk factors for LBW in a large multi-ethnic and socio-economically
      disadvantaged population. Data from 3242 mothers, who attended the Well Baby
      Clinic (Southwestern Sydney, Australia) for the first time, were analysed in
      relation to their demographic characteristics and socio-economic indices. The
      overall birthweight was 3377 +/- 577 g (mean +/- SD). In multiple linear
      regression analysis, smoking during pregnancy, marital status, parity, and
      country of birth were independently associated with birth weight. According to
      this analysis, lower birth weight was associated with mothers who had smoked
      during pregnancy (by 215.2 +/- 18.6 g), who were single (46.9 +/- 21 g), and of
      Asian background (108.5 +/- 38.2 g). However, higher parity was associated with
      significantly higher birth weight. The presence of each factor was coded as 1 and
      the absence, 0. A 'risk score' was then derived by summing up the individual
      scores. When birth weight was classified as 'low birth weight' (defined as those
      with birth weight being less than 2500 g) or normal birth weight, the overall
      prevalence of LBW was 1.9%. Each unit increase in the risk score was associated
      with a 1.9-fold (95% confidence interval: 1.5-2.6) increase in the risk of LBW.
      These data suggest that apart from marital status, ethnicity and parity, maternal
      smoking is the single most important preventable risk factors for LBW.

PMID- 12800949
TI  - Seroprevalence of hepatitis C virus infection and its association with natural
      infection of hepatitis B virus among preschool children in Taiwan.
AB  - Taiwan is a hyperendemic area of hepatitis B virus (HBV) infection where chronic
      hepatitis B is the most important cause of liver cirrhosis and hepatoma. Since,
      diagnostic kit for detecting hepatitis C virus (HCV) infection has been
      developed, HCV was found to be another important etiology of chronic liver
      disease. In order to study the seroprevalence of HCV infection among preschool
      children after mass hepatitis B vaccination program in Taiwan, a community-based
      survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas, and
      two aboriginal areas randomly selected through stratified sampling. Serum
      specimens of 2538 preschool children were screened for the HCV antibodies (anti
      HCV) by a commercially available third-generation microparticle enzyme
      immunoassay and for HBV markers by radioimmunoassay methods. The multivariate
      adjusted odd ratios (ORm) with their 95% confidence intervals (CI) were estimated
      through the multiple logistic regression analysis. A total of 58 children were
      anti-HCV seropositive, giving a prevalence of 2.3%. The prevalence of anti-HCV
      was 1.0% (5 of 484) among aboriginal children, a significantly decreased
      seroprevalence compared with those among other ethnic groups after multivariate
      adjustment. Boys had a higher anti-HCV seroprevalence, but not statistically
      significantly different from girls (ORm: 1.6; 95% CI: 0.9-2.8; p = 0.08). The
      seroprevalence of the age group of 3-4 years was lower than that of the age group
      of 5-6 years (ORm: 2.2; 95% CI: 1.1-4.2; p = 0.02). After multivariate
      adjustment, preschool children with natural HBV infection had a higher anti-HCV
      seroprevalence, but not statistically significantly different from those without
      natural HBV-infection (ORm: 2.6; 95% CI: 0.9-7.4; p = 0.08 for HBV-infected vs.
      uninfected). HCV infection varies with gender, residential area, and natural HBV
      infection. HCV and HBV might share common transmission routes in Taiwan.

PMID- 12800950
TI  - Hepatitis C virus infection in Lebanese patients with B-cell non-Hodgkin's
      lymphoma.
AB  - Several studies from many countries have reported a high prevalence (> 9%) of
      hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin lymphoma (B
      NHL) suggesting a possible etiological role of HCV in the development of B-NHL.
      Data from the United Kingdom and Turkey, however, did not confirm these
      observations. To determine the prevalence of HCV infection in patients with B
      cell lymphoma in Lebanon, a controlled study was conducted in which 318 Lebanese
      patients were investigated. These included 35 patients with B-NHL, 63 patients
      with various malignant conditions (control group 1) and 220 patients with non
      malignant conditions (control group 2). Samples were tested in duplicates for
      antibodies to HCV (anti-HCV) by enzyme-linked immunosorbant assay (ELISA). None
      of the 318 patients investigated were anti-HCV positive. Based on our findings,
      it can be concluded, that, there is no sufficient evidence to indicate that HCV
      plays role in the development of B-NHL in Lebanese patients. Predisposing factors
      in lymphoproliferative disorders are numerous including both genetic and
      environmental factors that could vary from one geographic region to another.

PMID- 12800951
TI  - Seroprevalence of hepatitis B and C in subjects admitted to a cardiology clinics
      in Turkey.
AB  - A seroepidemiological study was conducted to assess the seroprevalence of
      hepatitis B surface antigen (HBs Ag) and antibodies to hepatitis C virus (Anti
      HCV) in 14,196 patients hospitalized in our cardiology clinics. Threehundred and
      fifty five (355) patients (2.43%) were found to be positive for HBs Ag, a hundred
      and sixty six (166) patients (1.09%) were positive for Anti-HCV and ten patients
      (0.07%) were positive for both. The presence of HBs Ag and Anti-HCV was similar
      in patients living in rural and urban areas. The presence of risk factors was
      greater in the patients with Anti-HCV. The prevalences of HBs Ag and Anti-HCV
      were found to be comparable with those reported in other mediterranean countries
      in Europe.

PMID- 12800952
TI  - Seroprevalence of infection by Coxiella burnetii in Canary Islands (Spain).
AB  - OBJECTIVES:  THE AIMS OF OUR STUDY WERE: (i) to know the seroprevalence of
      Coxiella burnetii infection in the Canary Islands, (ii) to evaluate its
      epidemiologic features and (iii) to compare the rates of seroprevalence using two
      different cut-offs (1:20 and 1:80) for the diagnosis of past infection. METHODS:
      We analysed a representative sample of the canarian population. 662 sera were
      tested. For the detection of IgG and IgM antibodies against C. burnetii phase II
      antigens an immuofluorescence assay was used. The serologic screening for IgG
      detection begun with a 1:20 dilution. A titer of IgG > or = 1:80 along with a
      negative IgM were used as criteria for previous infection. RESULTS: At an IgG
      antibody titer against C. burnetii of 1:80 as diagnostic for past infection, the
      observed global seroprevalence was 21.5%. If the cut-off used was 1:20, the
      observed prevalence increased up to 35.8% (p = 0.001). Significantly different
      seroprevalence rates were obtained at these different cut-offs when results were
      analysed for groups of age and socioeconomic status, but not for either the
      island of origin or for farmers. CONCLUSION: Our results strongly suggest that
      Coxiella burnetii infection is endemic in all the Canary Islands. Although it is
      more frequent in males above 30 years old, it do affect people of all ages, and
      thus it should be borne in mind in the face of any acute febrile syndrome.

PMID- 12800953
TI  - Detection of Coxiella burnetii in ticks collected in Slovakia and Hungary.
AB  - A total of 235 adult ticks collected from vegetation in Slovakia and Hungary in
      1998-2000 were tested for Coxiella burnetii by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). C. burnetii was identified
      in six ticks of Ixodes ricinus, Dermacentor marginatus, and Haemaphysalis
      concinna species.

PMID- 12800954
TI  - Epidemiology of human brucellosis in a rural area of north-western Peloponnese in
      Greece.
AB  - A case-control study was conducted in a rural area of Achaia in western Greece to
      examine the risk factors of brucellosis. The participants in the study were 414
      (7.5% of the whole population of the investigated municipality). The cases (n =
      140) were defined by clinical symptoms and confirmed by a positive standard
      agglutination test (SAT). All cases have been diagnosed between January 1997 and
      March 1999 either by physicians of the Local Health Center or by private
      practitioners. Two criteria were basic to establish the disease. The first one
      was clinical symptoms such as fever, fatigue, arthralgia and generalized aches
      and the second was a titer of SAT at least 1:160. Controls (n = 274) were matched
      with cases for age and gender in a 1:2 ratio. Approximately collection of
      controls was performed among those presented to the local Health Center for other
      diseases. Data were collected by the same physician via a personal interview and
      analyzed by logistic regression models. The overall incidence of the disease in
      the region was found to be 1110/100,000. Taking 'no ownership of animals' and 'no
      contact of animals' as the reference category, the strongest risk factor was
      trauma during animal delivery with an odds ratio (OR): 24.3; 95% confidence
      interval (CI): 8.8-67.5 following by absence of stables (OR: 14.4; 95% CI: 4.7
      44.1). After application of multivariate stepwise analysis the adjusted risk
      factors remaining in the model were the place of residence (OR: 1.8; 95% CI: 1.1
      3.1), professional occupation with animals (OR: 2.4; 95% CI: 1.2-4.8), absence of
      stables (OR: 9.1; 95% CI: 2.2-38.7) and trauma during animal delivery (OR: 11.2;
      95% CI: 3.2-39.1). Consumption of cheese from pasteurized milk or consumption of
      cheese matured for over 3 months was found to be a protective factor (OR: 0.27;
      95% CI: 0.11-0.67). The detection of brucellosis in animals is essential for the
      prevention of the disease. In addition efficient preventive measures should be
      established in order to eliminate the disease.

PMID- 12800955
TI  - Boutonneuse fever in Portugal: 1995-2000. Data of a state laboratory.
AB  - From 1995 through 2000, 3239 clinical samples were tested for rickettsiosis at
      the Center for Vectors and Infectious Diseases Research--National Health
      Institute in Portugal. Boutonneuse fever due to R. conorii Malish or R. conorii
      Israel was laboratory confirmed in 374 samples (11.5%). Clinical and
      epidemiological features are discussed.

PMID- 12800956
TI  - Folic acid prevents more than neural tube defects: a registry-based study in the
      northern Netherlands.

PMID- 12800957
TI  - Ambulatory blood pressure monitoring: technology with a purpose.

PMID- 12800959
TI  - Does long-term anticoagulation improve function after stroke?

PMID- 12800958
TI  - Possible dangerous interaction of oxycontin and carisoprodol.

PMID- 12800960
TI  - Acute abdominal pain in children.
AB  - Acute abdominal pain in children presents a diagnostic dilemma. Although many
      cases of acute abdominal pain are benign, some require rapid diagnosis and
      treatment to minimize morbidity. Numerous disorders can cause abdominal pain. The
      most common medical cause is gastroenteritis, and the most common surgical cause
      is appendicitis. In most instances, abdominal pain can be diagnosed through the
      history and physical examination. Age is a key factor in evaluating the cause;
      the incidence and symptoms of different conditions vary greatly over the
      pediatric age spectrum. In the acute surgical abdomen, pain generally precedes
      vomiting, while the reverse is true in medical conditions. Diarrhea often is
      associated with gastroenteritis or food poisoning. Appendicitis should be
      suspected in any child with pain in the right lower quadrant. Signs that suggest
      an acute surgical abdomen include involuntary guarding or rigidity, marked
      abdominal distention, marked abdominal tenderness, and rebound abdominal
      tenderness. If the diagnosis is not clear after the initial evaluation, repeated
      physical examination by the same physician often is useful. Selected imaging
      studies also might be helpful. Surgical consultation is necessary if a surgical
      cause is suspected or the cause is not obvious after a thorough evaluation.

PMID- 12800961
TI  - The basic Z-plasty.
AB  - Z-plasty is a plastic surgery technique that is used to improve the functional
      and cosmetic appearance of scars. With this technique, it is possible to redirect
      a scar into better alignment with a natural skin fold or the lines of least skin
      tension. Contracted scars may be lengthened with this technique. Z-plasty
      involves the creation of two triangular flaps of equal dimension that are then
      transposed. Basic z-plasty flaps are created using an angle of 60 degrees on each
      side, which can lengthen a scar by 50 to 70 percent and reorient the direction of
      the central wound by 90 degrees. Keeping the length and angle of each flap
      precisely the same is key to avoiding mismatched flaps that may be difficult to
      close. Some possible complications of z-plasty include flap necrosis, hematoma
      formation under the flaps, wound infection, trapdoor effect, and sloughing of the
      flap caused by high wound tension.

PMID- 12800962
TI  - Use of atypical antipsychotic drugs in patients with dementia.
AB  - Increasingly, atypical antipsychotic drugs are prescribed for elderly patients
      with symptoms of psychosis and behavioral disturbances. These symptoms often
      occur in patients with Alzheimer's disease, other dementias, or Parkinson's
      disease. As the average age of Americans increases, the prevalence of Alzheimer's
      disease and Parkinson's disease will rise accordingly. Although nonpharmacologic
      treatments for behavioral disturbances should be tried first, medications often
      are needed to enable the patient to be adequately cared for. Current guidelines
      recommend using risperidone and olanzapine to treat psychosis in patients with
      Alzheimer's dementia. Quetiapine and clozapine are recommended for treatment of
      psychosis in patients with Parkinson's disease. Additional research is needed for
      a recently approved agent, ziprasidone. To minimize side effects, these
      medications should be started at low dosages that are increased incrementally.
      Drug interactions, especially those involving the cytochrome P450 system, must be
      considered. Clozapine's potentially lethal side effects limit its use in the
      primary care setting. Informed use of atypical antipsychotic drugs allows family
      physicians to greatly improve quality of life in elderly patients with dementia
      and behavior disturbances.

PMID- 12800963
TI  - Automated ambulatory blood pressure monitoring: clinical utility in the family
      practice setting.
AB  - Although the percentage of patients who are treated for hypertension has
      increased, the percentage of those who demonstrate control of blood pressure has
      declined. As a result of this trend, clinicians may increasingly rely on
      ambulatory blood pressure monitoring to improve the diagnosis and treatment of
      hypertension. Studies confirm that ambulatory blood pressure monitoring devices
      more accurately reflect a patient's blood pressure and correlate more closely
      with end-organ complications than blood pressure levels measured in the
      physician's office. Discriminate use of this technology in specific clinical
      circumstances assists in identifying patients at risk for hypertension and may
      result in improved outcomes in this subset of patients. Ambulatory blood pressure
      monitoring may be particularly helpful in clinical situations such as borderline
      hypertension, white-coat hypertension, apparent drug resistance, hypotensive
      symptoms from medications or autonomic dysfunction, episodic hypertension, and
      evaluation of antihypertensive efficacy.

PMID- 12800964
TI  - Information from your family doctor. Using an ambulatory blood pressure monitor.

PMID- 12800965
TI  - Helicobacter pylori infection.

PMID- 12800966
TI  - Photo quiz. Generalized pruritus without relief.

PMID- 12800967
TI  - Information from your family doctor. Endometrial cancer.

PMID- 12800968
TI  - Information from your family doctor. Pap smears: when yours is slightly abnormal.

PMID- 12800969
TI  - Information from your family doctor. Ovarian cyst.

PMID- 12800974
TI  - AAP issues screening recommendations to identify hearing loss in children.

PMID- 12800975
TI  - Emergency response.

PMID- 12800977
TI  - Comparative analysis of Dp427-deficient mdx tissues shows that the milder
      dystrophic phenotype of extraocular and toe muscle fibres is associated with a
      persistent expression of beta-dystroglycan.
AB  - The cell biological hypothesis of Duchenne muscular dystrophy assumes that
      deficiency in the membrane cytoskeletal element dystrophin triggers a loss in
      surface glycoproteins, such as beta-dystroglycan, thereby rendering the
      sarcolemmal membrane more susceptible to micro-rupturing. Secondary changes in
      ion homeostasis, such as increased cytosolic Ca2+ levels and impaired luminal
      Ca2+ buffering, eventually lead to Ca2+-induced myonecrosis. However, individual
      muscle groups exhibit a graded pathological response during the natural time
      course of x-linked muscular dystrophy. The absence of the dystrophin isofom Dp427
      does not necessarily result in a severe dystrophic phenotype in all muscle
      groups. In the dystrophic mdx animal model, extraocular and toe muscles are not
      as severely affected as limb muscles. Here, we show that the relative expression
      and sarcolemmal localization of the central trans-sarcolemmal linker of the
      dystrophin-glycoprotein complex, beta-dystroglycan, is preserved in mdx
      extraocular and toe fibres by means of two-dimensional immunoblotting and
      immunofluorescence microscopy. Thus, with respect to improving myology
      diagnostics, the relative expression levels of beta-dystroglycan appear to
      represent reliable markers for the severity of secondary changes in dystrophin
      deficient fibres. Immunoblotting and enzyme assays revealed that mdx toe muscle
      fibres exhibit an increased expression and activity of the sarcoplasmic reticulum
      Ca2+-ATPase. Chemical crosslinking studies demonstrated impaired calsequestrin
      oligomerization in mdx gastrocnemius muscle indicating that abnormal
      calsequestrin clustering is involved in reduced Ca2+ buffering of the dystrophic
      sarcoplasmic reticulum. Previous studies have mostly attributed the sparing of
      certain mdx fibres to the special protective properties of small-diameter fibres.
      Our study suggests that the rescue of dystrophin-associated glycoproteins, and
      possibly the increased removal of cytosolic Ca2+ ions, might also play an
      important role in protecting muscle cells from necrotic changes.

PMID- 12800976
TI  - Loss of function and impaired degradation of a cataract-associated mutant
      connexin50.
AB  - A mutant human connexin50 (hCx50), hCx50P88S, has been linked to cataracts
      inherited as an autosomal dominant trait. The functional, biochemical and
      cellular behavior of wild-type and mutant hCx50 were examined in transfected
      cells. hCx50P88S was unable to induce gap junctional currents by itself, and it
      abolished gap junctional currents when co-expressed with wild-type (wt) hCx50.
      Cells transfected with hCx50P88S showed cytoplasmic accumulations of Cx50
      immunoreactivity in addition to staining at appositional membranes; these
      accumulations did not significantly co-localize with markers for the endoplasmic
      reticulum, Golgi apparatus, lysosomes, endosomes or vimentin filaments.
      Immunoelectron microscopy studies localized hCx50P88S to cytoplasmic membrane
      stacks in close vicinity to the endoplasmic reticulum. In contrast, aggresome
      like accumulations were induced by treatment of wt hCx50-transfected cells with
      proteasomal inhibitors. The formation of hCx50P88S accumulations in transiently
      transfected cells was not blocked by treatment with Brefeldin A suggesting that
      they form before Cx50 transits through the Golgi apparatus to the plasma
      membrane. Treatment of HeLa-hCx50P88S cells with cycloheximide demonstrated the
      presence of a very stable pool of hCx50P88S. Taken together, these results
      suggest that the P to S mutation at amino acid residue 88 causes a defect that
      leads to decreased degradation and subsequent accumulation of hCx50P88S in a
      cellular structure different from aggresomes.

PMID- 12800978
TI  - Agonist-dependent trafficking of alpha2-adrenoceptor subtypes: dependence on
      receptor subtype and employed agonist.
AB  - Many G protein-coupled receptors (GPCRs) are internalized from the plasma
      membrane after agonist exposure. Previously, marked agonist-induced
      internalization of human alpha2A- and alpha2B-adrenergic receptors (AR) was
      observed in transfected neuronal rat pheochromocytoma (PC12) cells; alpha2A- and
      alpha2B-AR were internalized into partly distinct intracellular vesicles (Olli
      Lahdesmaki et al., J. Neurosci. 19, 9281-9288, 1999). In this paper, the extent
      of alpha2-AR internalization was quantitated in human embryonic kidney (HEK-293)
      and PC12 cells by combined application of cell surface biotinylation and ELISA
      methods, which allow measurement of protein trafficking in intact, differentiated
      and undifferentiated cells. Significant subtype-specific (but not cell type
      dependent) trafficking of human alpha2-AR was observed by quantitation and
      immunocytochemistry. Agonist-induced sequestration of alpha2B-AR was markedly
      reduced after blocking the formation of clathrin-coated vesicles by hyperosmotic
      sucrose pretreatment. The sequestration of alpha2A-AR was partly inhibited after
      sucrose pretreatment but could be further reduced after inhibiting the formation
      of both clathrin-coated and caveolin vesicles by combined pretreatment with
      hyperosmotic sucrose and filipin. Differences were also observed in the recycling
      of alpha2A- and alpha2B-AR. The extent of maximal agonist-induced sequestration
      in PC12 cells was not directly dependent on relative agonist efficacy.

PMID- 12800979
TI  - Mitochondrial and nuclear localization of kanadaptin.
AB  - Kanadaptin has originally been isolated as a kidney Cl-/HCO3- anion exchanger 1
      (kAE1)-binding protein. Initial studies suggested, that in the kidney of the
      rabbit kanadaptin is expressed exclusively in all epithelial cells of the
      collecting duct. Transcripts of kanadaptin were also found in tissues not
      expressing kAE1, indicating additional roles for kanadaptin. With respect to
      this, we could recently demonstrate translocation of kanadaptin into the nucleus
      of mammalian cells in a nuclear localization sequence- and importin-dependent
      manner (Hubner et al., Biochem. J. 361, 287-296, 2002). In this study, we provide
      evidence, that kanadaptin is widely expressed in many tissues and that expression
      of kanadaptin in the mouse occurs early in embryonic development. In rat kidney
      we found the most intense immunofluorescence for kanadaptin in cells of the
      proximal tubule, consistent with the detection by in situ hybridization of high
      amounts of kanadaptin messenger RNA in proximal tubule cells. Immunostaining
      revealed localization of kanadaptin in two subcellular locations, nuclei and
      mitochondria. Whereas nuclear localization was demonstrated in virtually all
      cells, mitochondrial staining was restricted to certain cell types. Nuclear
      staining was only seen in cryosections, whereas mitochondrial staining was
      observed in both cryosections and semithin sections of freeze-dried plastic
      embedded tissue. In the kidney mitochondrial staining was particularly prominent
      in proximal tubular epithelium. Most surprisingly, in the collecting duct
      epithelium (including acid-secreting intercalated cells) only negligible
      immunostaining, if at all, could be observed. Immunoelectron microscopy showed
      immunolabelling of the entire cross-sectional profile of mitochondria
      (matrix/inner membrane). Mitochondrial localization of kanadaptin was further
      documented by immunoblotting of mitochondria-enriched cellular fractions.
      Utilizing an interspecies heterokaryon assay, we could further demonstrate that
      kanadaptin has nuclear export activity. Thus, kanadaptin can be regarded to be a
      highly mobile nucleocytoplasmic shuttling and multilocalizing protein, but its
      role in mammalian cells remains still obscure.

PMID- 12800980
TI  - CDK2 is involved in the S-phase lengthening induced by glucocorticoids in normal
      human lymphocytes.
AB  - Involvement of CDK2 in glucocorticoid-mediated S-phase lengthening was analyzed
      in this work. Dexamethasone (DXM) treatment of PHA-stimulated lymphocytes induced
      a decrease in CDK2 mRNA expression without any change in mRNA stability. This
      glucocorticoid-induced decrease in CDK2 mRNA expression could be suppressed by
      cycloheximide treatment. These results support the hypothesis of an indirect
      effect of DXM at the transcriptional level. Furthermore, CDK2 protein expression
      also decreased while the rate of protein synthesis and stability remained
      unchanged, suggesting a second post-translational level of regulation with the
      preferential degradation of a CDK2 protein stock fraction. The analysis of co
      precipitated proteins showed that glucocorticoids induced modifications of
      protein complex composition. We found i) a preservation of the linkage capability
      of CDK2 for cyclin E and A, ii) a relative increase in p27kip1 linkage, and iii)
      a decrease in p21waf1 complexed with CDK2. As a consequence of CDK2 decrease and
      modifications of protein complex composition, pRb and histone H1 kinase activity
      of CDK2 was profoundly decreased. All these results pinpoint the role of CDK2 in
      glucocorticoid-induced S-phase lengthening and the potential activator role of
      p21waf1 for CDK2 in human lymphocytes.

PMID- 12800982
TI  - Effect of doxazosin GITS on blood pressure in hypertensive and normotensive
      patients: a review of hypertension and BPH studies.
AB  - Doxazosin is an effective treatment for patients with hypertension, benign
      prostatic hyperplasia (BPH) and the two comorbidly. In its standard formulation,
      doxazosin requires a multistep titration regimen to minimize a possible first
      dose effect. A new extended-release gastrointestinal therapeutic system (GITS)
      formulation of doxazosin was developed to improve the pharmacokinetic profile of
      the parent compound and to reduce or eliminate the need for dose titration and
      the potential risk of overdosing. This review presents an analysis of the effect
      of doxazosin GITS monotherapy on blood pressure (BP) and tolerability, as
      evaluated in four clinical trials, two conducted in patients with stage 1 to
      stage 2 hypertension and two in patients with BPH with different levels of BP.
      Doxazosin GITS was as effective as doxazosin standard and more effective than
      placebo was in reducing and controlling BP in patients with hypertension. Among
      normotensive patients with BPH, no clinically significant effect on BP was
      observed and no episodes of syncope were recorded. Doxazosin GITS was generally
      better tolerated than doxazosin standard, based on the proportion of patients
      with adverse events and those withdrawing due to adverse events. Moreover, the
      GITS formulation eliminated the need for titration in most patients. Doxazosin
      GITS is an effective and well-tolerated treatment in patients with hypertension
      and/or BPH and without heart failure or clinical coronary heart disease and has
      advantages over doxazosin standard in terms of a simpler dosing regimen and
      improved tolerability.

PMID- 12800981
TI  - Progress on isolation and short-term ex-vivo culture of highly purified non
      apoptotic human intestinal epithelial cells (IEC).
AB  - Intestinal epithelial cells (IEC) form the largest surface of the human body and
      are of pivotal importance to digest and absorb nutrients. Furthermore these cells
      play a critical role shielding the organism against microorganisms and toxins
      present in the intestinal lumen. It is therefore not surprising that a large
      group of researchers take great interest in the study of these cells. However, to
      date it is a challenge to purify viable primary human intestinal epithelial cells
      and it has been even more fastidious to maintain IEC in culture ex-vivo as IEC
      undergo apoptosis within hours due to loss of cell anchorage ('anoikis')
      following the isolation process. Over recent years the authors aimed to
      continuously improve the isolation technique for primary IEC, allowing a simple,
      effective and rapid isolation of highly purified non-apoptotic human IEC. In this
      study the newly improved method is presented and applied to establish ex-vivo
      cultures of highly purified, fully viable primary IEC displaying important
      functional properties, making these cells amenable for ex-vivo research on
      primary human intestinal epithelial cells.

PMID- 12800983
TI  - Improved tolerability of the dihydropyridine calcium-channel antagonist
      lercanidipine: the lercanidipine challenge trial.
AB  - The objective of this 8-week open-label study was to compare the tolerability of
      lercanidipine, a dihydropyridine calcium-channel antagonist (CA), with that of
      other CAs in the treatment of hypertension. Subjects already taking amlodipine,
      felodipine, nifedipine gastrointestinal therapeutic system (GITS), or
      nitrendipine and experiencing CA-specific adverse effects (AEs) were switched to
      lercanidipine for 4 weeks and then rechallenged with their initial treatment for
      4 weeks. Results showed that at comparable levels of BP, lercanidipine was
      associated with a significantly lower incidence of ankle edema, flushing, rash,
      headache and dizziness compared with other CAs (p < 0.001). After 4 weeks of
      lercanidipine, mean systolic blood pressure (SBP)/diastolic blood pressure (DBP)
      was 142.1/86.7 mmHg. After rechallenge with other CAs for 4 weeks, mean SBP/DBP
      was 141.1/86.7 mmHg. In this open-label study, lercanidipine compared with other
      CA seems to provide a significant improvement in tolerability with comparable
      antihypertensive effect.

PMID- 12800984
TI  - Effects of nifedipine on carotid and femoral arterial wall thickness in
      previously untreated hypertensive patients.
AB  - BACKGROUND: Experimental and clinical evidence suggests that calcium-channel
      blockers may retard the atherosclerotic process after long-term treatment.
      Whether these effects exist after intermediate-term treatment in hypertensive
      patients is mainly unknown. OBJECTIVE: To determine the 26-week effects of the
      long-acting calcium-channel blocker nifedipine on intima media thickness (IMT) in
      newly found hypertensive patients. DESIGN: Open-label study with blinded end
      point analysis. METHODS: From a population survey, 131 previously untreated mild
      hypertensives (4 x systolic blood pressure between 160 and 220 mmHg and/or
      diastolic blood pressure between 95 and 115 mmHg) were included. Patients were
      treated with long-acting nifedipine 30-60 mg targeted to reach a predetermined
      drop in blood pressure. Prior to and after 26 weeks of treatment, IMT was
      measured by ultrasonography in the carotid and femoral artery. The combined mean
      maximal far wall IMT was used as primary endpoint. Change from baseline was
      evaluated by paired t-test in an intention-to-treat analysis. RESULTS: The mean
      maximal far wall IMT at baseline was 1.03 +/- 0.23 mm, and decreased by 0.078 mm
      (95% confidence interval, CI 0.044-0.111) after treatment. Regression analysis,
      including baseline IMT and changes of blood pressure, showed that reduction of
      IMT was mostly influenced by baseline IMT (p < 0.001; model R2 = 0.1).
      CONCLUSION: Our observations show that 26 weeks of nifedipine treatment inhibits
      IMT progression in these newly found hypertensive patients. This effect was
      mostly seen in arterial walls with highest IMT before treatment, suggesting that
      patients with highest cardiovascular risk benefit most of antihypertensive
      treatment.

PMID- 12800985
TI  - Evaluation of the efficacy and tolerability of nebivolol versus lisinopril in the
      treatment of essential arterial hypertension: a randomized, multicentre, double
      blind study.
AB  - The main objective of this study was to compare the anti-hypertensive efficacy
      and safety of nebivolol (5 mg once daily) and lisinopril (20 mg once daily) given
      for 12 weeks in patients with mild to moderate essential hypertension. Fourteen
      centres participated in this randomized, double-blind parallel group study. Sixty
      eight patients with uncomplicated mild-to-moderate hypertension were randomized,
      and sixty-five were eligible for the analysis of efficacy (intention-to-treat).
      Hypertensive patients were newly diagnosed, or previous antihypertensive therapy
      was withdrawn at least 1 month before active treatment, and were included in the
      study if their diastolic blood pressure (DBP) was > 95 and < 114 mmHg. The age
      range was 24-65 years. The primary endpoints of the study were: (i) response
      rate: patients were defined as "normalized" responders if their blood pressure
      values were < 140/90 mmHg, or as "non-normalized" responders if the reduction in
      blood pressure was 10 mmHg or more, compared with baseline; (ii) changes in
      sitting blood pressure at the end of the study. The secondary endpoints were:
      standing blood pressure and sitting or standing heart rate (HR). Results showed
      that baseline sitting DBP was significantly different between groups. Analysis of
      covariance of the raw data performed with baseline as covariate demonstrated that
      the DBP and HR values were significantly lower in the nebivolol group at the 8th
      week. However, when an analysis of variance for repeated measures was performed,
      a significant reduction in sitting systolic blood pressure (SBP) (p < 0.0001),
      DBP (p < 0.0001) and HR (p < 0.0001) was observed throughout the study in both
      groups. No difference was observed between treatments, although for DBP, a
      significant interaction between treatment-weeks was observed (p = 0.016). There
      was also a statistically significant difference in favour of the nebivolol group
      in the distribution of responders and non-responders at week 8. Lisinopril and
      nebivolol were equally well tolerated. In conclusion, nebivolol was slightly more
      effective, in comparison with lisinopril, in terms of reduction in DBP. This
      greater efficacy was obtained without any increase in adverse effects, since both
      treatments were equally well tolerated.

PMID- 12800987
TI  - Administration of nifedipine CR immediately after awakening prevents a morning
      surge in hypertensive patients. Case report of three cases.
AB  - Although the blood pressure-lowering action of some long-acting calcium
      antagonists may last more than 24 h, some patients taking this drug still
      experience a morning surge, i.e. an early morning increase in blood pressure. We
      evaluated this morning surge in three hypertensive patients with morning surge
      after administration of antihypertensive drugs including nifedipine CR.
      Nifedipine CR is one of the once-a-day formulations of nifedipine, which after
      administration, results in two peaks in the plasma concentration of nifedipine.
      The first concentration peak of occurs 3 h after administration and the second
      around 12 h after intake. When the time of intake of nifedipine CR was changed
      from after breakfast to immediately after awakening, the morning surge was
      suppressed in these patients without the use of other drugs such as alpha- or
      beta-blockers. Administration of nifedipine CR immediately after awakening is one
      option that can be used to prevent morning surge as well as to control blood
      pressure throughout the day.

PMID- 12800986
TI  - Valsartan/hydrochlorothiazide is effective in hypertensive patients inadequately
      controlled by valsartan monotherapy.
AB  - OBJECTIVE: This double-blind parallel-group randomized trial compared the
      efficacy and safety of fixed combination valsartan 160 mg/hydrochlorothiazide
      12.5 mg (Val 160/HCTZ 12.5) once daily (o.d.) and Val 160/hydrochlorothiazide 25
      mg (Val 160/HCTZ 25) o.d. vs Val 160 o.d. monotherapy in patients with mild-to
      moderate essential hypertension not adequately controlled with valsartan
      monotherapy. METHOD: A total of 2002 patients whose BP was inadequately
      controlled with 4 weeks of Val 160 mg o.d. monotherapy were randomized to
      treatment for 8 weeks with Val 160 (n = 666), Val 160/HCTZ 12.5 (n = 670) or Val
      160/HCTZ 25 (n = 666). RESULTS: Active treatment significantly reduced BP in all
      groups over the 12 weeks of the study (p < 0.001). The greatest reductions were
      achieved with Val 160/HCTZ 25. Reductions were 10.8, 12.8 and 14.2 mmHg (sitting
      diastolic blood pressure) and 15.7, 19.4 and 21.8 mmHg (sitting systolic blood
      pressure), for the Val 160, Val 160/HCTZ 12.5 and Val 160/HCTZ 25 groups,
      respectively. Responder rates were high in all groups (49%, 62% and 68%). In
      elderly patients (> or = 65 years) responder rates of 70% were achieved with Val
      160/HCTZ 25. All treatments were well tolerated, in all patient groups.
      CONCLUSIONS: The combination of Val 160 plus HCTZ 12.5 or HCTZ 25 provides
      effective and well-tolerated treatment in patients inadequately controlled after
      4 weeks of monotherapy. In elderly patients a responder rate of 70% was achieved
      with Val 160/HCTZ 25.

PMID- 12800988
TI  - Proteolytic fungi isolated from decayed and damaged raw tomatoes and implications
      associated with changes in pericarp pH favorable for survival and growth of
      foodborne pathogens.
AB  - Raw and minimally processed high-acid fruits and vegetables are considered to be
      at low or no risk for supporting growth of foodborne pathogens. The potential
      increase in the pH of tissues as a result of fungal growth, however, may enhance
      the potential for survival and growth. We examined 77 decayed and 138 damaged,
      raw, ripe tomatoes for the presence of yeasts and molds that produce proteolytic
      enzymes and other metabolites that can potentially increase the pH of pulp
      tissue. The pH of decayed and sound radial pericarp tissues (pulp) of decayed
      tomatoes ranged from 4.7 to 7.8 (mean = 6.2) and 4.3 to 5.8 (mean = 5.0),
      respectively, whereas the pH of damaged and sound pericarp of damaged tomatoes
      ranged from 4.2 to 7.8 (mean = 5.2) and 4.2 to 8.0 (mean = 4.9), respectively.
      The pH of sound pericarp of 8.5% of decayed tomatoes and 3.4% of damaged
      tomatoes, respectively, was > 5.41. In contrast, the pH of 70% of the decayed
      tissue and 18% of the damaged tissue was > 5.41. Fungal isolates (n = 371)
      recovered from decayed and damaged tomatoes on dichloran rose bengal
      chloramphenicol agar were examined for proteolytic activity on gelatin agar and
      standard methods caseinate agar. One hundred eight (29%) of the isolates
      exhibited proteolytic activity on one or both differential media; 96 (89%) were
      molds, and 12 (11%) were yeasts. The pH of both media increased at the edge of
      proteolytic fungal colonies. Growth of proteolytic isolates from decayed tomatoes
      on tomato juice agar (pH = 4.3) and on the surface of tomato juice (pH = 4.1)
      caused an increase in mean pH values at the colony/medium interface to 7.2 and
      6.4, respectively. Results show that some fungi capable of infecting raw
      tomatoes, as well as the mycoflora incident on tomato surfaces, can increase the
      pH of pericarp and juice to levels favorable for growth of most foodborne
      pathogenic bacteria.

PMID- 12800989
TI  - Decontamination of seeds for seed sprout production by high hydrostatic pressure.
AB  - Garden cress, sesame, radish, and mustard seeds immersed in water were treated
      with high pressure (250, 300, 350, and 400 MPa) for 15 min at 20 degrees C. After
      treatment, percentages of seeds germinating on water agar were recorded for up to
      11 days. Of the seeds tested, radish seeds were found to be the most pressure
      sensitive, with seeds treated at 250 MPa reaching 100% germination 9 days later
      than untreated control seeds did. Garden cress seeds, on the other hand, were the
      most pressure resistant, with seeds treated at 250 MPa reaching 100% germination
      1 day later than untreated control seeds did. Garden cress sprouts from seeds
      treated at 250 and 300 MPa also took about 1 day longer to reach average sprout
      length than sprouts from untreated control seeds did, indicating that sprout
      growth was not retarded once germination had occurred. Garden cress seeds were
      inoculated with suspensions of seven different bacteria (10(7) CFU/ml) and
      processed with high pressure. Treatment at 300 MPa (15 min, 20 degrees C)
      resulted in 6-log reductions of Salmonella Typhimurium, Escherichia coli MG1655,
      and Listeria innocua, > 4-log reductions of Shigella flexneri and pressure
      resistant E. coli LMM1010, and a 2-log reduction of Staphylococcus aureus.
      Enterococcus faecalis was virtually not inactivated. For suspensions of the gram
      positive bacteria, similar levels of inactivation in water in the absence of
      garden cress seeds were found, but the inactivation of E. coil LMM1010 and S.
      flexneri in water in the absence of garden cress seeds was significantly less
      extensive. These data suggest that garden cress seeds contain a component that
      acts synergistically with high hydrostatic pressure against gram-negative
      bacteria.

PMID- 12800990
TI  - Pathogenicity of enterohemorrhagic Escherichia coli in neonatal calves and
      evaluation of fecal shedding by treatment with probiotic Escherichia coli.
AB  - The pathogenicity and fecal shedding of enterohemorrhagic Escherichia coli (EHEC)
      O26:H11, O111:NM, and O157:H7 were compared in calves (< 1 week of age) with or
      without prior treatment with probiotic bacteria (competitive exclusion E. coli).
      Three groups of 12 to 14 calves were used for these treatments. Half of the
      calves in each group were perorally administered 10(10) CFU of probiotic bacteria
      per calf, and, 2 days thereafter, 10(8) CFU of a five-strain mixture with one of
      the three EHEC serotypes per calf were administered to each calf. None of the
      EHEC serotypes caused clinical disease,and neither gross nor microscopic lesions
      attributable to EHEC were detected in control or probiotic-treated calves at
      necropsy. In calves administered E. coli O157:H7, fecal shedding was greatly
      reduced (> 6 log10 CFU/g) by 8 days after administration, and there was no
      significant difference (P > 0.05) in fecal shedding of E. coli O157:H7 between
      probiotic-treated and untreated control groups at that time. In contrast, control
      calves perorally administered E. coil of serotypes O111:NM or O26:H11 continued
      to shed substantial populations (10(2.1) to 10(6) CFU/g of feces and 10(2.5) to
      10(4.9) CFU/g of feces, respectively) throughout 7 days postadministration of
      EHEC. In both groups administered either E. coli O111:NM or O26:H11,
      significantly less (P < 0.05) EHEC was isolated from feces at 7 days
      postadministration of EHEC and at necropsy from theprobiotic-treated group than
      from the untreated control group. Overall, neonatal calves shed in the feces from
      1 to 7 days following peroral administration of EHEC greater populations of E.
      coli O111:NM and O26:H111 than E. coli O157:H7. In addition, treatment of calves
      with probiotic E. coli reduced fecal shedding of E. coli O111:NM and O26:H11 in
      most calves.

PMID- 12800991
TI  - Enterococcus faecalis and Enterococcus faecium isolates from milk, beef, and
      chicken and their antibiotic resistance.
AB  - The occurrence and antibiotic resistance of enterococci, especially Enterococcus
      faecalis and Enterococcus faecium, in milk, beef, and chicken in Gaborone,
      Botswana, were studied. Enterococci were isolated from these sources with the use
      of bile esculin agar and identified with API 20 Strep kits. Antibiotic resistance
      was determined by the disk diffusion method. The antibiotics tested were
      vancomycin, teicoplanin, ampicillin, tetracycline, and cephalothin. Among the
      1,467 enterococci isolated from the samples, E. faecalis (46.1%) and E. faecium
      (29.0%) were found to be the predominant species. Other enterococcal species made
      up 25% of the isolates. More than 96 and 97% of the E. faecalis and E. faecium
      isolates, respectively, were found to be resistant to ampicillin. Almost 34,
      27.3, and 22.4% of the E. faecalis isolates from milk, beef, and chicken,
      respectively, were also resistant to cephalothin. The percentages of E. faecium
      isolates that were found to be resistant to cephalothin were 32.8, 16.9, and
      17.3% for milk, beef, and chicken, respectively. Resistance to vancomycin was
      widespread. It was found that 18.8, 7.8. and 13.1% of the E. faecalis isolates
      from milk, beef, and chicken samples, respectively, were resistant to vancomycin.
      In contrast, 32.8, 24.7, and 30.7% of the E. faecium isolates from milk, beef,
      and chicken samples, respectively, were resistant to vancomycin. Isolates that
      were resistant to multiple drugs were found in relatively large numbers.

PMID- 12800992
TI  - A survey of antibiotic resistance in Micrococcaceae isolated from Italian dry
      fermented sausages.
AB  - The transfer of bacteria that are resistant to antimicrobial agents or resistance
      genes from animals to humans via the food chain is increasingly a problem.
      Therefore, it is important to determine the species and the numbers of bacteria
      involved in this phenomenon. For this purpose, 148 strains of microstaphylococci
      were isolated from three types of Italian dry fermented sausages. Eight of 148
      strains belonged to the genera Kocuria and Micrococcus. The remaining 140 strains
      belonged to 11 different species of the genus Staphylococcus. The species most
      frequently isolated was Staphylococcus xylosus, followed by Staphylococcus
      saprophyticus and Staphylococcus aureus. Antibiotic resistance levels differed
      among the species and depended on the strain origin. Microstaphylococci were
      generally susceptible to beta-lactams, but 12 strains were resistant to
      methicillin, 8 were resistant to oxacillin, and 9 were resistant to penicillin G.
      No resistance was observed for aminoglicosides and cephalosporines. Many strains
      were resistant to sulfonamide, colistin suphate, tetracyclin, and bacitracin. Two
      strains of S. aureus, four strains of S. xylosus, and one strain of
      Staphylococcus sciuri were able to grow in the presence of 8 microg of vancomycin
      per g, but all strains were susceptible to teicoplanin. Twenty-two
      microstaphylococci were resistant to at least five of the tested antibiotics. The
      multiresistant strain S. aureus 899 was unaffected by eight antibiotics,
      including vancomycin and methicillin, indicating that a more prudent use of
      antibiotics in animal husbandry and better hygienic conditions during production
      should be encouraged because they can play a major role in reducing the incidence
      of such multiresistant microorganisms and the possible spread of the genetic
      elements of their resistance.

PMID- 12800993
TI  - Microbiological monitoring of sheep carcass contamination in three Swiss
      abattoirs.
AB  - At three Swiss abattoirs, 580 sheep carcasses were examined at 10 sites by the
      wet-dry double-swab technique. The aim of this study was to obtain data on
      microbiological contamination at the abattoirs and to develop a procedure for
      monitoring slaughter hygiene. Median aerobic plate counts (APCs) (log CFU/cm2)
      ranged from 2.5 to 3.8, with the brisket and neck sites showing the most
      extensive contamination. Enterobacteriaceae were detected on 68.1% of the
      carcasses and in 15.2% of the samples. The proportion of positive results ranged
      from 2.6% (for the hind leg and the flank at abattoir C) to 42.2% (for the
      perineal area at abattoir A). The percentage of samples testing positive for stx
      genes by polymerase chain reaction was 36.6%. A significant relationship between
      APC and the detection of Shiga toxin-producing Escherichia coli (STEC) was found
      for abattoirs A and B (depending on sampling site), whereas a significant
      relationship between Enterobacteriaceae and STEC detection was confirmed only for
      abattoir A (P < 0.05). In 57.1% of the 56 isolated non-O157 strains, stx2 genes
      were detected, and most of them were stx2d positive. Additional virulence factors
      were detected in 50% of the STEC strains, with 8.9% of these strains being eae
      positive, 50% being EHEC-hlyA positive, and 3.6% being astA positive. For the
      determination of carcass contamination, the monthly examination of 10 sheep
      carcasses for APC and Enterobacteriaceae counts in the neck, brisket, and
      perineal areas is recommended. This procedure is a valuable tool for the
      verification of slaughter hygiene according to hazard analysis critical control
      point principles.

PMID- 12800994
TI  - Enteric illness in Ontario, Canada, from 1997 to 2001.
AB  - Enteric illness is a common problem worldwide. In Ontario (population of 11.4
      million, 2001 Census of Canada), laboratory-confirmed cases of "reportable"
      enteric diseases are reported to local health units. Public health staff members
      investigate these illnesses and subsequently report details to the Ministry of
      Health and Long-Term Care through an electronic reporting system. From 1997 to
      2001, 44,451 sporadic cases of illness attributable to eight enteric pathogens
      (Campylobacter, Salmonella, verotoxin-producing Escherichia coli, Yersinia,
      Shigella, hepatitis A, Listeria, and Clostridium botulinum) were reported. This
      number was less than the 56,690 cases reported from 1992 to 1996. Campylobacter
      accounted for the highest annual average incidence rate at 42.3 cases per 100,000
      persons, with Salmonella following at 22.6, verotoxin-producing E. coli at 3.7,
      Yersinia at 3.0, Shigella at 2.7, hepatitis A at 2.3, and Listeria at 0.3. The 4
      months from June to September accounted for almost half (46.5%) of all cases. For
      74.0% of the outbreaks associated with these eight enteric pathogens, foodborne
      contamination was identified as the mode of transmission. Poultry and other meat
      items accounted for 68.4% of the food items when food was identified as the
      vehicle. Admittedly, the "foods" and "modes of transmission" identified may have
      been subject to investigator bias based on previous knowledge. The most common
      risk setting, which was reported in approximately half of the cases, was private
      homes; travel-associated illness and restaurants were the second and third most
      frequently reported risk settings at 24.6 and 14.1%, respectively. Findings from
      this study suggest that public health efforts should be directed toward safe food
      handling in the home during the summer months.

PMID- 12800995
TI  - Survival and recovery of Listeria monocytogenes on ready-to-eat meats inoculated
      with a desiccated and nutritionally depleted dustlike vector.
AB  - Dust from construction was theorized to serve as a vector for L. monocytogenes
      transmission to ready-to-eat (RTE) meats after heat processing but before
      packaging. A five-strain Listeria monocytogenes culture including serotype 4b was
      continually stressed on a sand vector under four sets of nutritionally depleted
      and dry conditions to simulate postprocessing contamination by dustlike
      particulates. The stresses included that associated with sand stored at different
      temperatures (10 and 22 degrees C) and levels of humidity (40% relative humidity
      [RH], 88% RH, or complete desiccation). Irradiated RTE meats, including
      frankfurters, bologna, chopped ham, and deli-style roast beef, were inoculated
      with the L. monocytogenes-contaminated sand every 2 to 3 days over a period of 1
      1/2 months. After inoculation, the RTE meats were vacuum packed and stored at 4
      degrees C for 24 h. Populations of L. monocytogenes were enumerated by surface
      plating on nonselective and selective media to recover cells on the basis of the
      different stresses presented (osmotic or antibiotic). L. monocytogenes was
      demonstrated to be capable of surviving on the sand vector for > 151 days at 10
      degrees C and 88% RH, 136 days at 10 degrees C and 0% RH, 73 days at 22 degrees C
      and 40% RH, and 82 days at 22 degrees C and 0% RH. These results show that under
      the most conservative scenario, the 73-day-old L. monocytogenes-contaminated sand
      was able to attach to and be recovered from the RTE meats. This study illustrated
      that dust contaminated with L. monocytogenes, once in contact with meat surfaces,
      can survive and grow, posing a health hazard to consumers.

PMID- 12800996
TI  - Acid adaptation and starvation effects on Shiga toxin production by Escherichia
      coli O157:H7.
AB  - Reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent
      assay (ELISA), and gene fusion were used to determine differences in the
      expression of stx-II mRNA and the production of mature Stx protein following acid
      adaptation or starvation of Escherichia coli O157:H7 (ATCC 43895) and an isogenic
      rpoS mutant (FRIK 816-3) under static conditions and with shaking. The expression
      of stx-II mRNA in acid-adapted and starved cells was more extensive than that in
      nonstressed control cells. This effect was more pronounced for the rpoS mutant.
      Oxygenation (incubation with shaking) increased stx-II mRNA expression for both
      strains relative to the level of expression obtained with static conditions.
      ELISA results indicated that Stx production was enhanced more in the rpoS mutant
      than in its wild-type parent strain and that oxygenation enhanced Stx production
      for both strains but there were no detectable differences between stressed and
      nonstressed cells of either strain. The monitoring of the gene product of Stx-II
      alone with the use of stx-IIAB::lacZ gene fusions confirmed the induction of
      aeration and the absence of a stress effect for both the wild type and the rpoS
      mutant. These results indicate that oxygen enhances stx-II mRNA expression and
      Stx production in E. coli O157:H7. Stress conditions such as acid adaptation and
      starvation enhance stx-II toxin mRNA levels but do not enhance subsequent Stx
      toxin production.

PMID- 12800997
TI  - Improved model based on the Weibull distribution to describe the combined effect
      of pH and temperature on the heat resistance of Bacillus cereus in carrot juice.
AB  - The effect of pH and temperature on the thermal inactivation of different strains
      of Bacillus cereus was modeled. Inactivation tests were carried out in carrot
      broth, following a full factorial design at four levels for temperature (from 90
      to 105 degrees C, depending on the strain) and pH (6.2, 5.8, 5.2, and 4.7).
      Individual inactivation curves were analyzed by applying the Weibull model
      function (with percent discrepancy close to 20% for most cases), and the effects
      of pH and temperature on the scale parameter (designated D(beta)) and the shape
      parameter (beta) were also studied. Temperature and pH did not have a significant
      effect on the shape parameter (beta). The effect of temperature on the scale
      parameter was modeled by the zeta concept. The scale parameter decreased with pH,
      although the behavior of the strains was not homogeneous. Two global models with
      a small number of parameters were developed, providing a satisfactory description
      of the thermal inactivation of B. cereus, with percent discrepancy ranging from
      18 to 25%.

PMID- 12800998
TI  - Acid adaptation does not promote survival or growth of Listeria monocytogenes on
      fresh beef following acid and nonacid decontamination treatments.
AB  - The objective of this study was to evaluate the survival and growth of acid
      adapted and nonadapted Listeria monocytogenes inoculated onto fresh beef
      subsequently treated with acid or nonacid solutions. Beef slices (2.5 by 5 by 1
      cm) from top rounds were inoculated with acid-adapted or nonadapted L.
      monocytogenes (4.6 to 5.0 log CFU/cm2) and either left untreated (control) or
      dipped for 30 s in water at 55 degrees C, water at 75 degrees C, 2% lactic acid
      at 55 degrees C, or 2% acetic acid at 55 degrees C. The beef slices were vacuum
      packaged and stored at 4 or 10 degrees C and were analyzed after 0, 7, 14, 21,
      and 28 days of storage. Dipping in 75 degrees C water, lactic acid, and acetic
      acid resulted in immediate pathogen reductions of 1.4 to 2.0, 1.8 to 2.6, and 1.4
      to 2.4 log CFU/cm2, respectively. After storage at 10 degrees C for 28 days,
      populations of L. monocytogenes on meat treated with 55 degrees C water increased
      by ca. 1.6 to 1.8 log CFU/cm2. The pathogen remained at low population levels
      (1.6 to 2.8 log CFU/cm2) on acid-treated meat, whereas populations on meat
      treated with 75 degrees C water increased rapidly, reaching levels of 3.6 to 4.6
      log CFU/cm2 by day 14. During storage at 4 degrees C, there was no growth of the
      pathogen for at least 21 days in samples treated with 55 and 75 degrees C water,
      and periods of no growth were longer for acid-treated samples. There were no
      differences between acid-adapted and nonadapted organisms across treatments with
      respect to survival or growth. In conclusion, the dipping of meat inoculated with
      L. monocytogenes into acid solutions reduced and then inhibited the growth of the
      pathogen during storage at 4 and 10 degrees C, while dipping in hot water allowed
      growth despite initial reductions in pathogen contamination. The results of this
      study indicate a residual activity of acid-based decontamination treatments
      compared with water-based treatments for refrigerated (4 degrees C) or
      temperature-abused (10 degrees C) lean beef tissue in vacuum packages, and these
      results also indicate that this activity may not be counteracted by prior acid
      adaptation of L. monocytogenes.

PMID- 12800999
TI  - Ionizing radiation sensitivity of Listeria monocytogenes ATCC 49594 and Listeria
      innocua ATCC 51742 inoculated on endive (Cichorium endiva).
AB  - Ionizing radiation inactivates the pathogenic bacteria that can contaminate leafy
      green vegetables. Leaf pieces and leaf homogenate of endive (Cichorium endiva)
      were inoculated with the pathogen Listeria monocytogenes (ATCC 49594) or Listeria
      innocua (ATCC 51742), a nonpathogenic surrogate bacterium. The radiation
      sensitivity of the two strains was similar, although L. innocua was more
      sensitive to the type of suspending leaf preparation. During refrigerated storage
      after irradiation, the population of L. monocytogenes on inoculated endive was
      briefly suppressed by 0.42 kilogray (kGy), a dose calibrated to achieve a 99%
      reduction. However, the pathogen regrew after 5 days until it exceeded the
      bacterial levels on the control after 19 days in storage. Treatment with 0.84
      kGy, equivalent to a 99.99% reduction, suppressed L. monocytogenes throughout
      refrigerated storage. Doses up to 1.0 kGy had no significant effect on the color
      of endive leaf material, regardless of whether taken from the leaf edge or the
      leaf midrib. The texture of leaf edge material was unaffected by doses up to 1.0
      kGy, whereas the maximum dose tolerated by leaf midrib material was 0.8 kGy.
      These results show that endive leaves may be treated with doses sufficient to
      achieve at least a 99.99% reduction of L. monocytogenes with little or no impact
      on the product's texture or color.

PMID- 12801000
TI  - Inhibition of Listeria monocytogenes in pH-adjusted pasteurized liquid whole egg.
AB  - Although the transmission of L. monocytogenes to humans via pasteurized egg
      products has not been documented, L. monocytogenes and other Listeria species
      have been isolated from commercially broken raw liquid whole egg (LWE) in both
      the United States and Ireland. Recent Listeria thermal inactivation studies
      indicate that conventional minimal egg pasteurization processes would effect only
      a 2.1- to 2.7-order-of-magnitude inactivation of L. monocytogenes in LWE; thus,
      the margin of safety provided by conventional pasteurization processes is
      substantially smaller for L. monocytogenes than for Salmonella species (a 9-order
      of-magnitude process). The objective of this study was to evaluate the inhibitory
      effects of nisin on the survival and growth of L. monocytogenes in refrigerated
      and pH-adjusted (pH 6.6 versus pH 7.5) ultrapasteurized LWE and in a liquid model
      system. The addition of nisin (1,000 IU/ml) to pH-adjusted ultrapasteurized LWE
      reduced L. monocytogenes populations by 1.6 to > 3.3 log CFU/ml and delayed (pH
      7.5) or prevented (pH 6.6) the growth of the pathogen for 8 to 12 weeks at 4 and
      10 degrees C. Bioactive nisin was detected in LWE at both pH values for 12 weeks
      at 4 degrees C. In subsequent experiments, Listeria reductions of > 3.0 log
      CFU/ml were achieved within 24 h in both LWE and broth plus nisin (500 IU/ml) at
      pH 6.6 but not at pH 7.5, and antilisterial activity was enhanced when nisin was
      added as a solution rather than in dry form.

PMID- 12801001
TI  - Weibull distribution function based on an empirical mathematical model for
      inactivation of Escherichia coli by pulsed electric fields.
AB  - The pulsed electric field inactivation kinetics of Escherichia coli suspended in
      orange juices with three different concentrations of carrot juice (0, 20, and
      60%) was studied. Electric field strengths ranged from 25 to 40 kV/cm, and
      treatment times ranged from 40 to 340 micros. Experimental data were fitted to
      Bigelow, Hulsheger, and Weibull distribution functions, and the Weibull function
      provided the best fit (with the lowest mean square error). The dependency of each
      model's kinetic constant on electric field strength and carrot juice
      concentration was studied. A secondary model was developed to describe the
      relationship of Weibull parameters a and n to electric field strength and carrot
      juice concentration. An empirical mathematical model based on the Weibull
      distribution function, relating the natural logarithm of the survival fraction to
      treatment time, electric field strength, and carrot juice concentration, was
      developed. Parameters were estimated by a nonlinear regression. The results of
      this study indicate that the error rate for the model's predictions was 6.5% and
      that the model was suitable for describing E. coli inactivation.

PMID- 12801002
TI  - Evaluation of a select strain of Lactobacillus delbrueckii subsp. lactis as a
      biological control agent for pathogens on fresh-cut vegetables stored at 7
      degrees C.
AB  - Raw vegetables inoculated with selected pathogenic bacteria were treated with a
      strain of Lactobacillus delbrueckii subsp. lactis, which was selected for its
      ability to produce hydrogen peroxide at refrigerated temperatures. The vegetables
      inoculated included broccoli, cabbage, carrots, and lettuce. Each vegetable was
      rinsed, chopped, and stored under conditions similar to those used for ready-to
      eat vegetables sold at retail. Portions of each vegetable were separately
      inoculated with one of two pathogenic bacteria, Escherichia coli O157:H7 or
      Listeria monocytogenes. Prior to packaging, one portion of each inoculated
      vegetable was treated with a cell suspension of the selected strain of L.
      delbrueckii subsp. lactis. The vegetables were stored at 7 degrees C for 6 days.
      The populations of pathogens and lactobacilli on each sample were enumerated on
      storage days 0, 3, and 6. Although populations of L. delbrueckii subsp. lactis
      remained at high levels during storage, there was no noticeable antagonistic
      action against the pathogens under conditions similar to those used for these
      products at the retail level. Each pathogen survived on all vegetables throughout
      storage. Further testing revealed that there was apparently sufficient catalase
      activity in the cut vegetables to destroy enough of the hydrogen peroxide to
      prevent antagonistic action against the pathogens.

PMID- 12801003
TI  - Reduction of bacteria on pork carcasses associated with chilling method.
AB  - In addition to reducing the temperature of pork carcasses immediately after
      slaughter and before fabrication, blast chilling (snap chill) or conventional
      chilling can reduce bacterial populations associated with fresh meats. However,
      there is little information on bacteria survival resulting from the freeze or
      chill injury of meat products. In this study, porcine fecal slurries with and
      without pathogens (Listeria monocytogenes, Salmonella Typhimurium, and
      Campylobacter coli) were inoculated onto skin-on and skin-off pork surfaces and
      subjected to industry-specific blast or conventional chilling conditions. A thin
      agar layer method was used for the recovery of freeze- or chill-injured cells.
      Test results indicated that there were no statistically significant (P > 0.05)
      differences between blast and conventional chilling treatments with respect to
      the reduction of high and low inoculation levels of mesophilic aerobic bacteria,
      total coliforms, or Escherichia coli on either skin-on or skin-off surfaces.
      Chilling treatments did not differ significantly (P > 0.05) with respect to their
      ability to reduce low (3 log10 CFU/cm2) levels of L. monocytogenes and Salmonella
      Typhimurium. However, C. coli was reduced to undetectable levels, even after
      enrichment, on pork surfaces inoculated with low levels (3 log10 CFU/cm2) and
      subjected to blast chilling. Blast and conventional chilling treatments were more
      effective against all pathogenic bacterial populations when pork surfaces where
      inoculated at high levels (5 log10 CFU/cm2). The effects of chilling techniques
      on microbial populations could provide pork processors with an additional
      intervention for pork slaughter or information to modify and/or improve the
      chilling process. The information obtained from this study has the potential to
      serve as a means of producing a microbiologically safer product.

PMID- 12801004
TI  - Inactivation by ionizing radiation of Salmonella enteritidis, Salmonella
      infantis, and Vibrio parahaemolyticus in oysters (Crassostrea brasiliana).
AB  - Irradiation is considered one of the most efficient technological processes for
      the reduction of microorganisms in food. It can be used to improve the safety of
      food products, and to extend their shelf lives. Oysters are considered one of the
      most important vehicles for pathogenic bacteria because of their feeding
      characteristics. The aim of this study was to evaluate the influence of a gamma
      radiation process on high levels of Salmonella Enteritidis, Salmonella Infantis,
      and Vibrio parahaemolyticus incorporated by oysters (Crassostrea brasiliana), as
      well as the effects of the process on the survival of the oysters and on their
      sensory attributes. The oysters were exposed to gamma radiation (60Co) in doses
      ranging from 0.5 to 3.0 kGy. A dose of 3.0 kGy was generally sufficient to reduce
      the level of Salmonella serotypes by 5 to 6 log10 units. A dose of 1.0 kGy was
      sufficient to produce a 6-log10 reduction in the level of V. parahaemolyticus.
      The highest irradiation dose did not kill the oysters or affect their sensory
      attributes. Hence, a dose of 3.0 kGy can be considered effective in inactivating
      Salmonella and V. parahaemolyticus in oysters without changing their odor,
      flavor, or appearance.

PMID- 12801005
TI  - Evaluation of consumer-style cooking methods for reduction of Escherichia coli
      O157:H7 in ground beef.
AB  - The objective of this study was to evaluate the thermal inactivation of
      Escherichia coli O157:H7 in ground beef cooked to an internal temperature of 71.1
      degrees C (160 degrees F) under conditions simulating consumer-style cooking
      methods. To compare a double-sided grill (DSG) with a single-sided grill (SSG),
      two different cooking methods were used for the SSG: for the one-turnover (OT
      SSG) method, a patty was turned once when the internal temperature reached 40
      degrees C, and for the multiturnover (MT-SSG) method, a patty was turned every 30
      s. Patties (100 g, n = 9) inoculated with a five-strain mixture of E. coli O157:
      H7 at a concentration of 10(7) CFU/g were cooked until all three temperature
      readings (for two sides and the center) for a patty were 71.1 degrees C. The
      surviving E. coli O157:H7 cells were enumerated on sorbitol MacConkey (SMAC) agar
      and on phenol red agar base with 1% sorbitol (SPRAB). The order of the cooking
      methods with regard to the cooking time required for the patty to reach 71.1
      degrees C was as follows: DSG (2.7 min) < MT-SSG (6.6 min) < OT-SSG (10.9 min).
      The more rapid, higher-temperature cooking method was more effective (P < 0.01)
      in destroying E. coli O157:H7 in ground beef. E. coli O157:H7 reduction levels
      were clearly differentiated among treatments as follows: OT-SSG (4.7 log10 CFU/g)
      < MT-SSG (5.6 log10 CFU/g) < DSG (6.9 log10 CFU/g). Significantly larger numbers
      of E. coil O157:H7 were observed on SPRAB than on SMAC agar. To confirm the
      safety of ground beef cooked to 71.1 degrees C, additional patties (100 g, n = 9)
      inoculated with lower concentrations of E. coli O157:H7 (10(3) to 10(4) CFU/g)
      were tested. The ground beef cooked by the OT-SSG method resulted in two (22%) of
      nine samples testing positive after enrichment, whereas no E. coli O157:H7 was
      found for samples cooked by the MT-SSG and DSG methods. Our findings suggest that
      consumers should be advised to either cook ground beef patties in a grill that
      cooks the top and the bottom of the patty at the same time or turn patties
      frequently (every 30 s) when cooking on a grill that cooks on only one side.

PMID- 12801006
TI  - Activation and inactivation of Talaromyces macrosporus ascospores by high
      hydrostatic pressure.
AB  - The effect of high hydrostatic pressure treatment (with pressures of up to 700
      MPa) on Talaromyces macrosporus ascospores was investigated. At 20 degrees C,
      pressures of > or = 200 MPa induced the activation and germination of dormant
      ascospores, as indicated by increased colony counts for ascospore suspensions
      after pressure treatment and the appearance of germination vesicles and tubes.
      Pressures of > 400 MPa additionally sensitized the ascospores to subsequent heat
      treatment. At pressures of > 500 MPa, activation occurred in a few minutes but
      was followed by inactivation with longer exposure. However, even with the most
      extreme pressure treatment, a fraction of the ascospore population appeared to
      resist both activation and inactivation, and the maximal achievable reduction of
      ascospores was on the order of 3.0 log10 units. Pressure-induced ascospore
      activation at 400 MPa was temperature dependent, with minimum activation at 30 to
      50 degrees C and > or = 10-fold higher activation levels at 10 to 20 degrees C
      and at 60 degrees C, but it was not particularly pH dependent over a pH range of
      3.0 to 6.0. Pressure inactivation at 600 MPa, in contrast, was pH dependent, with
      the inactivation level being 10-fold higher at pH 6.0 than at pH 3.0. Observation
      of pressure-treated and subsequently dried spores with the use of light and
      scanning electron microscopy revealed a collapse of the spore structure,
      indicating a loss of the spore wall barrier properties. Finally, pressure
      treatment sensitized T. macrosporus ascospores to cell wall lytic enzymes.

PMID- 12801007
TI  - Comparison of a modified digestion assay with trichinoscopy for the detection of
      Trichinella larvae in pork.
AB  - A pepsin-HCl digestion assay and two compressorium techniques (trichinoscopy) for
      the identification of swine muscle tissue containing low levels of Trichinella
      larvae were compared as part of the test validation process for quality assurance
      purposes. Compressoria read with a stereomicroscope detected more larvae (P <
      0.0001, n = 57) and more tissues (P = 0.0047, n = 57) than did compressoria read
      with a projection microscope (trichinoscope). The digestion assay evaluated was
      3.2 times as likely as the best compressorium technique to identify a positive
      tissue when these procedures were used to test 1 g of infected muscle (P < 0.001;
      95% confidence interval for the odds ratio, 2.0 to 5.4; n = 161 and n = 189,
      respectively). Detection by trichinoscopy improved as the number of larvae in
      tissues increased to > 2 larvae per g, but trichinoscopy was less sensitive than
      the digestion assay regardless of the tissue larval load. These data indicate
      that the quality controlled digestion assay used in this study is more sensitive
      than trichinoscopic techniques in the detection of tissues containing low levels
      of Trichinella larvae.

PMID- 12801008
TI  - Potential of Bacillus cereus for producing an emetic toxin, cereulide, in bakery
      products: quantitative analysis by chemical and biological methods.
AB  - A method for the direct quantitative analysis of cereulide, the emetic toxin of
      Bacillus cereus, in bakery products was developed. The analysis was based on
      robotized extraction followed by quantitation of cereulide by liquid
      chromatography-mass spectrometry and an assay of toxicity by the boar sperm
      motility inhibition test. The bioassay and the chemical assay gave comparable
      results, demonstrating that the extracted cereulide was in a biologically active
      form. Cereulide was formed when cereulide-producing B. cereus strains were
      present at > or = 10(6) CFU/g in products with water activity values of > 0.953
      and pHs of > 5.6. Rice-containing pastries accumulated high contents of cereulide
      (0.3 to 5.5 microg/g [wet weight]) when stored at nonrefrigeration temperatures
      (21 to 23 degrees C). Cereulide was not formed in products stored at
      refrigeration temperatures (4 to 8 degrees C). Cereulide is not inactivated by
      heating during food processing. Therefore, direct analysis of this toxin in food
      is preferable to cultivating methods for assessing the risk of food poisoning by
      emetic B. cereus.

PMID- 12801009
TI  - Development of two multiplex polymerase chain reactions for the detection of
      enterotoxigenic strains of Staphylococcus aureus isolated from foods.
AB  - Two multiplex polymerase chain reactions were developed for the detection of
      enterotoxigenic strains of Staphylococcus aureus: one multiplex reaction for the
      simultaneous detection of enterotoxigenic strains type A (entA), type B (entB),
      and type E (entE) and another for the simultaneous detection of enterotoxigenic
      strains type C (entC) and type D (entD). Both reactions were standardized with
      the use of the reference enterotoxigenic strains of S. aureus: FRI 722, producer
      of staphylococcal enterotoxin (SE) type A (SEA); FRI 1007, producer of SEB; FRI
      137, producer of SEC1; FRI 472, producer of SED; and FRI 326, producer of SEE.
      Optimized methods were used to determine the presence of enterotoxigenic types
      for 51 S. aureus strains isolated from meat (sausage, ham, and chorizo) and dairy
      (powdered milk and cheese) products by the Baird-Parker technique. The
      enterotoxigenic capacities of the strains were determined by the indirect enzyme
      linked immunosorbent assay (ELISA) with the use of reference staphylococcal
      toxins and antitoxins. Fifty of the 51 strains isolated were enterotoxigenic and
      produced one to four enterotoxin types, with the most frequently produced types
      being SEA and SED. Levels of correlation between the presence of genes that code
      for the production of SE (as determined by polymerase chain reaction) and the
      expression of these genes (as determined by the indirect ELISA) were 100% for SEA
      and SEE, 86% for SEC, 89% for SED, and 47% for SEB.

PMID- 12801010
TI  - Real-time and conventional polymerase chain reaction systems based on the metallo
      carboxypeptidase inhibitor gene for specific detection and quantification of
      potato and tomato in processed food.
AB  - In this paper, a method for the specific detection and quantification of potato
      and tomato DNA in food samples with the use of conventional and real-time
      polymerase chain reaction (PCR) is described. This method is adequate for use in
      food quality routine assays involving highly processed samples for which very
      tiny amounts of DNA are expected. Detection was achieved by amplifying a region
      of the metallo-carboxypeptidase inhibitor gene from either the potato (PCI) or
      the tomato (MCPI) and by using specific primers complementary to the propeptide
      regions of these inhibitors, which were found to differ for the potato and tomato
      proproteins. Conventional and real-time PCR systems were based on the same potato
      or tomato-specific primer pairs, and quantification was carried out with a
      TaqMan chemistry-based probe. The methods developed proved to be very specific
      and sensitive and highly reliable for the identification and quantification of
      DNA from both plant species. In addition, the construction of plasmids pPAT and
      pTOM, suitable for use as external calibration standards for the elaboration of
      comparative amplification profiles, is reported. Limits of detection and
      quantification with the use of these plasmid standards are given. Specificity and
      copy number conservation among different cultivars were analyzed, and the
      reliability of these systems was tested through their application to the analysis
      of commercial food samples including potato and/or tomato as components.

PMID- 12801011
TI  - Response of Salmonella and Escherichia coli O157:H7 to UV energy.
AB  - To determine the efficacy of a UV light treatment at 253.7 nm (UVC light) on
      microbial growth, plates containing tryptic soy agar plus 50 ppm of nalidixic
      acid (TSAN) were inoculated with known concentrations of five-strain cocktails of
      Salmonella and Escherichia coli O157:H7 and subjected to different UVC
      treatments. The concentration of the cocktail inoculum was determined with TSAN
      prior to inoculation. Serial dilutions were carried out, and inoculation levels
      of 10(0) to 10(8) CFU/ ml were tested for each pathogen. Multiple replications of
      doses of UV light ranging from 1.5 to 30 mW/cm2 were applied to different
      cocktail concentrations, and doses of > 8.4 mW/cm2 resulted in a 5-log reduction
      of Escherichia coli O157:H7, while a 5-log reduction of Salmonella was observed
      with doses of > 14.5 mW/cm2. Results for both organisms yielded sigmoidal
      inactivation curves. UVC light is effective in reducing microbial populations of
      pathogens on agar surfaces.

PMID- 12801012
TI  - Antimicrobial properties of commercial annatto extracts against selected
      pathogenic, lactic acid, and spoilage microorganisms.
AB  - Annatto preparations are used to impart distinctive flavor and color to foods and
      are a primary colorant in dairy foods such as cheese and butter. There are
      several reports indicating that certain fractions of the annatto plant have
      biological activities against microorganisms of significance in food
      fermentation, food preservation, and human health. However, little is reported
      describing the nature of the antimicrobial compound(s) or their potential
      presence in commercial annatto colorant preparations. This study was conducted to
      determine whether commonly available annatto extracts are capable of influencing
      the outgrowth of selected lactic acid, spoilage, and pathogenic microorganisms.
      Disk diffusion and tube macrodilution techniques were used to determine the MICs
      and MBCs of double-strength water-soluble annatto extracts. Standard antibiotic
      disks were used as controls for the disk diffusion assay. The results demonstrate
      that annatto has an inhibitory effect on Bacillus cereus, Clostridium
      perfringens, and Staphylococcus aureus, with MICs of 0.08, 0.31, and 0.16%
      (vol/vol) and diameters of inhibition of 9 to 10, 12 to 13, and 15 to 16 mm,
      respectively. A concentration of 0.63% (vol/vol) inhibited the growth of
      Streptococcus thermophilus, Lactobacillus casei subsp. casei, Lactococcus lactis,
      and Paenibacillus polymyxa. The MICs for Listeria monocytogenes and Enterococcus
      durans were 1.25 and 2.5% (vol/vol), respectively. No activity was detected
      against Lactobacillus plantarum, Bifidobacterium bifidum, yeasts, or selected
      gram-negative bacteria.

PMID- 12801013
TI  - Comparison of eight phenotypic methods for subspecies characterization of
      thermophilic Campylobacter spp. isolated from pig liver.
AB  - Four hundred pork livers from bacon pigs (37 herds) obtained at six pig
      processing plants were studied to assess the Campylobacter contamination rate.
      Deep tissue areas were sampled immediately after evisceration. Approximately 6%
      of livers were infected with Campylobacter spp., including Campylobacter coli
      (67%), Campylobacter jejuni (30%), and Campylobacter lari (3%). The 60 resulting
      isolates (39 C. coli isolates, 19 C. jejuni isolates, and 2 C. lari isolates)
      employed in this study were characterized at the subspecies level in a comparison
      of eight phenotyping schemes, including four biotyping, two serotyping, and two
      phage-typing schemes. The Skirrow-Benjamin biotyping scheme produced two biotypes
      for C. jejuni, i.e., biotype 2 (95%) and biotype 1 (5%). The Lior biotyping
      scheme subdivided C. coli into biotype 1 (41%) and biotype 2 (59%), while biotype
      4 was the dominant type (95%) for C. jejuni. The Roop scheme allowed further
      differentiation of C. coli into three biovars, i.e., biovar 1 (57%), biovar 2
      (40%), and biovar 3 (3%), and it subdivided C. jejuni into two biotypes, i.e.,
      biovar 1 (95%) and biovar 2 (5%). Preston biotyping produced the largest degree
      of subspecies differentiation, with 18 C. coli biotypes and 7 C. jejuni biotypes
      being identified. The most common were biotypes 2650 and 6030, representing 18
      and 42% of all C. coli and C. jejuni isolates, respectively. The Penner-Hennessy
      serotyping scheme successfully serotyped 89% of the isolates, with 10 serotypes
      being identified; 30% of the serotypeable isolates were accounted for by Penner
      23, followed by Penner 20 (16%) and Penner 39 (14%). The Lior serotyping scheme
      successfully serotyped only 45% of the strains, and eight serogroups were
      identified, with Lior 36 (31%), Lior 20 (23%), and Lior 5 being the most
      frequent. The Preston scheme and the Khakhria-Lior phage-typing scheme were able
      to type 16 and 25% of the isolates, respectively. The Preston scheme produced
      three phage groups, i.e., 69 (56%), 90 (22%), and 116 (22%), and the Khakhria
      Lior scheme also produced three phage types, i.e., 44 (40%), 27 (33%), and 37
      (20%), as well as atypical lysis patterns (7%). The results of this study
      demonstrate the role of Preston biotyping in the phenotyping of isolates,
      particularly in diagnostic laboratories that have no access or limited access to
      molecular typing equipment.

PMID- 12801014
TI  - Characterization of a polymerase chain reaction-based approach for the
      simultaneous detection of multiple animal-derived materials in animal feed.
AB  - In this study, a polymerase chain reaction (PCR) primer set capable of amplifying
      a mitochondrial DNA segment of multiple species (cattle, sheep, goats, deer, and
      elk) whose rendered remains are prohibited from being fed to ruminants was
      characterized. However, the primer set also amplifies DNA derived from the
      rendered remains of pigs and horses, which are exempt from the feed ban. PCR
      amplicons derived from pig DNA have a restriction endonuclease site recognized by
      Hinf1, while the horse DNA-derived amplicon has a unique restriction endonuclease
      site recognized by HypCH4III. This "universal" PCR primer produced an amplicon
      with DNA extracted from dairy feed containing either bovine meat and bone meal or
      pig blood meal. Enzymatic digestion of the PCR amplicons from these feed samples
      with Hinf1 resulted in cleavage products only from samples containing pig blood
      meal. However, Hinf1 digestion of these amplicons was not complete. Further
      analysis of the pig blood meal with primers specific for bovine or porcine DNA
      demonstrated the presence of both bovine- and porcine-derived DNA. Enzymatic
      digestion confirmed these findings. Additional testing was conducted with dry dog
      food samples labeled as containing either lamb, chicken, turkey, or chicken and
      fish. The universal PCR primer produced an amplicon only for the dog food
      containing lamb meal. This paper is the first to describe a simplified approach
      for the detection of the prohibited species of concern in the feed ban.

PMID- 12801015
TI  - Effect of modified atmosphere packaging and irradiation in combination on content
      of nitrosamines in cooked pork sausage.
AB  - The effect of modified atmosphere packaging and irradiation in combination on
      nitrosodimethylamine (NDMA) and nitrosopyrrolidine (NPYR) levels in pork sausage
      was studied. Emulsion-type cooked pork sausage was manufactured and packaged in
      aerobic, CO2 (100%), N2 (100%), and CO2/N2 (25%/75%) environments, respectively,
      and irradiated at 0, 5, 10, and 20 kGy with gamma irradiation. The nitrosamine
      contents were significantly reduced by irradiation, and the reduction of
      nitrosamines was more extensive with modified atmosphere packaging than with
      aerobic packaging. The correlation coefficient between irradiation dose and
      nitrosamine content indicated that irradiation can reduce the levels of
      nitrosamines. The combination of irradiation and modified atmosphere packaging is
      effective in enhancing the chemical safety of sausage by reducing nitrosamines,
      if present, as well as enhancing the microbial safety of cooked pork sausage.

PMID- 12801016
TI  - Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, chlorinated
      pesticides (DDTs), hexachlorocyclohexane, and hexachlorobenzene residues in
      smoked seafood.
AB  - Smoked seafoods were screened for the presence of polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and other organochlorine
      compounds. Total PAH concentrations ranged from 46.5 ng/g (wet weight) for smoked
      swordfish to 124.0 ng/g (wet weight) for smoked herring. Among the carcinogenic
      PAHs, benzo(a)pyrene ranged from undetectable levels for several smoked fish to
      0.7 ng/g for Scottish salmon, dibenzo(ah)anthracene was not present in any of the
      samples analyzed, and benzo(a)anthracene was found in all samples and at
      particularly high levels in salmon (23.2 ng/g). Benzo(a)pyrene concentrations
      were below the tolerance limit for all samples. PCB concentrations for the
      different samples ranged from 2 to 30 ng/g. Chlorinated pesticides (DDTs: p,p'
      DDE, p,p'-DDT, o,p'-DDT, p,p'-DDD, and o,p'-DDD) were detected at levels ranging
      from 0.2 ng/g (wet weight) in bluefin tuna to 17.5 ng/g (wet weight) in salmon.
      Hexachlorocyclohexane isomers (alphaHCH + betaHCH + gammaHCH) were present in
      higher amounts in eels (6.5 ng/g) than in the other smoked fish. For 40% of the
      samples, PCB concentrations exceeded the limit fixed by the European Union, while
      pesticide levels were below the maximum acceptable limit proposed by the Food and
      Agriculture Organization.

PMID- 12801017
TI  - Student recruitment in allied health educational programs: the importance of
      initial source of contact.
AB  - As a part of a larger study on recruitment and marketing strategies adopted by
      allied health programs, this article examines the effect of initial source of
      information about allied health career opportunities on students' decisions to
      select and enroll in allied health programs. Using data obtained from 1,809
      students currently enrolled in six allied health disciplines, this investigation
      revealed that allied health students receive career information from various
      sources. Practicing health professionals are the most effective initial source of
      information for prospective allied health students. Prospective students are more
      inclined to enroll in allied health educational programs if they are encouraged
      to do so by a practitioner. Also, it was observed that 1) most students decide
      about their career interest at an early age; 2) their first-degree interest is
      not always the one they eventually pursue in college; and 3) the effect of
      initial source of information on enrollment decision varied by discipline.
      Contrary to a widely held assumption, only two groups of students (physical
      therapy and dental hygiene) identified high school counselors as an important
      source of initial information about allied health educational programs.

PMID- 12801018
TI  - The educational interaction between physical therapy and occupational therapy
      students.
AB  - The objectives of this study were to identify the prevalence of shared learning
      in U.S. physical therapy (PT) and occupational therapy (OT) education programs;
      determine what terminology is used for these courses; and identify perceived
      barriers, benefits, and challenges of the educational interactions. A survey,
      designed to collect information about the educational interaction between PT and
      OT students, was mailed to all program directors (n = 206) at each of the
      academic institutions (N = 103) in the United States with accredited or
      developing entry-level programs in PT and OT. A census study was conducted, and
      the entire study population received a survey. A total of 206 surveys were
      mailed, and 123 were retured (59.7% response rate). Of program directors, 40
      (67.8%) of the PT and 42 (65.6%) of the OT program directors reported that their
      students shared courses with each other. None of the PT and only 8 (12.5%) of the
      OT directors reported that students shared clinical experiences. The term
      interdisciplinary was used most frequently to refer to shared educational
      experiences. Benefits of shared learning included sharing resources,
      collaboration, learning about the other profession, and gaining respect for the
      other profession. Challenges to shared learning included resource constraints,
      curricular differences, competition and differences between disciplines,
      relevance of course work, and different faculty expectations. Barriers reported
      by program directors whose students did not engage in interdisciplinary education
      were resource constraints, curricular differences, faculty attitude, and failure
      of past attempts. A model of interdisciplinary education that seeks to instill
      collaboration and understanding among professions is difficult to implement
      without shared clinical experiences. Most students in entry-level PT and OT
      programs in the United States do not currently have the opportunity to practice
      the teamwork that will be essential when they enter their respective professions.

PMID- 12801019
TI  - Establishing a practice climate in academic settings.
AB  - This article describes an innovative educational approach that was introduced and
      developed in one occupational therapy program, favorably assessed by students,
      and promoted within the occupational therapy literature. A review of educational
      literature from other disciplines suggests that the approach characterized as
      creating a practice climate, may be useful to most allied health educators. We
      discuss (1) the meaning of the term practice climate, (2) the rationale for
      creating such a climate in larger classroom sessions, (3) nine process strategies
      that can establish this climate, and (4) an assessment of the approach by two
      groups of undergraduate students. Although introduced in a senior-level
      undergraduate course, the approach has merit for implementation in less advanced
      courses and in graduate education.

PMID- 12801020
TI  - Development and validation of a professional behavior assessment.
AB  - Allied health students must quickly socialize into a professional role as they
      transition from classroom to clinic. In addition to skill development, students
      must exhibit a host of professional behaviors that facilitate successful
      interaction with patients, families, and colleagues. There is a need for a valid,
      reliable assessment of professional behaviors that contribute to clinical
      competence. This study reports on the development and validation of a
      professional behavior assessment for occupational therapy students on a part-time
      clinical rotation (Level I). The Philadelphia Region Fieldwork Consortium (PRFC)
      Level I Student Evaluation was developed from an initial survey (n = 75) to
      generate an item pool, followed by a content review by a panel of experts (n = 5)
      to establish relevancy, clarity and content validity. This 12-item instrument was
      administered to 317 occupational therapy and occupational therapy assistant
      students. A principal component factor analysis and item analysis was conducted.
      Internal consistency reliability (Cronbach's alpha) was 0.89, with intra-rater
      reliability for the 12 items ranging from 0.68 for "written communication" to
      0.89 for "observation skills." The PRFC Level I Evaluation demonstrates
      discriminant validity, with students on their first clinical rotation scoring
      significantly (p < 0.001) lower than students on their third or fourth rotations,
      indicating a developmental process of professional socialization.

PMID- 12801021
TI  - Characteristics, perceptions, and other factors influencing physical therapist
      assistant program directors in 2001.
AB  - Little is known about program directors in physical therapist assistant (PTA)
      programs. This study describes the characteristics of program directors in PTA
      programs, such as time spent on responsibilities, influences on decision making,
      perceptions of current working relationships, and satisfaction with decision
      making. Program directors of 153 (57.5%) accredited PTA programs responded to the
      survey. The self-reported data were generated by a mail survey developed by the
      investigator that included 32 demographic items and 58 Likert-scale items to meet
      the purpose of the study. The data suggest that PTA program directors have
      average to extremely good levels of satisfaction with their positions and spend
      more time on student-related and accreditation/long range planning activities
      than they do on other activities. Information on years of experience and types of
      degrees suggest that respondents have a great deal of physical therapy experience
      but much less experience in teaching and administration within community
      colleges. This information may be valuable for people who seek, or who are
      recruited for, PTA program director positions. It provides a foundational
      database for periodic studies of PTA program directors. As enrollments and new
      programs stabilize and as new program directors are appointed, their impact on
      physical therapy education and the profession must be reevaluated.

PMID- 12801022
TI  - Integrating health promotion, patient education, and adult education principles
      with the older adult: a perspective for rehabilitation professionals.
AB  - With demographic changes and an increase in the number and proportion of older
      adults, there is now a greater demand for health promotion and patient education
      by rehabilitation professionals who are experts in their respective fields and
      who are knowledgeable about normal and pathologic aging. Older adults are more at
      risk for chronic illnesses and are interested in learning more about their own
      health. Many interrelationships between health promotion, patient education, and
      adult education exist in the context of rehabilitation for older adults. Changes
      in the U.S. health care system have decreased resources for long-term
      rehabilitation so that interventions must have the maximal impact possible.
      Health promotion and patient education are within the scope of practice of
      rehabilitation professionals, but the effectiveness of these efforts are
      diminished unless concepts and approaches for teaching and interacting with older
      adults are used. This commentary discusses the rationale for integrating these
      three aspects of patient care.

PMID- 12801023
TI  - The role of problem-based learning in the enhancement of allied health education.

PMID- 12801024
TI  - Evaluating the professional behaviors of entry-level occupational therapy
      students.

PMID- 12801025
TI  - The effect of an interdisciplinary community health project on student attitudes
      toward community health, people who are indigent and homeless, and team
      leadership skill development.
AB  - This study examined whether students' attitudes about community health practice,
      attitudes toward people who are indigent and homeless, and perceived leadership
      skills changed after participation in a planned interdisciplinary community
      health experience with an urban homeless or formerly homeless population. Data
      were collected from medicine, nursing, occupational therapy, physical therapy,
      and social work students who participated in the community health experiences and
      from students in these disciplines who did not participate in this curriculum.
      The interdisciplinary community health curriculum and practicum experiences,
      based on the Community Health Empowerment Model (CHEM), were designed and
      implemented by a coalition of community and academic partners. Students in the
      CHEM project self-selected into the curriculum and initially showed more positive
      attitudes about community health and indigent and homeless people than their
      peers not participating. Despite the CHEM students' positive initial attitudes,
      data from pretests and posttests revealed a significant positive change in their
      attitudes toward community health practice at the completion of the curriculum.

PMID- 12801026
TI  - Growing leaders for tomorrow: the University of Kentucky Administrative
      Internship Program.

PMID- 12801027
TI  - Developing cultural competence in occupational therapy and physical therapy
      education: a field immersion approach.

PMID- 12801028
TI  - Colonoscopy or barium enema for population colorectal cancer screening?
AB  - There is good evidence from faecal occult blood testing trials that detection and
      removal of non-advanced colorectal neoplasms can achieve a reduction in
      colorectal cancer mortality. Both colonoscopy and barium enema have potential
      advantages and disadvantages if implemented for population screening. The
      relative merits of each are discussed.

PMID- 12801029
TI  - Is artificial intelligence an intelligent choice for gastroenterologists?

PMID- 12801030
TI  - Helicobacter pylori testing in patients with peptic ulcer bleeding.

PMID- 12801031
TI  - A negative rapid urease test is unreliable for exclusion of Helicobacter pylori
      infection during acute phase of ulcer bleeding. A prospective case control study.
AB  - BACKGROUND: The reliability of the rapid urease test has not been proven in
      patients with peptic ulcer bleeding. Some studies show bad diagnostic results
      with the rapid urease test for gastrointestinal bleeding. AIMS: To evaluate the
      efficacy of the rapid urease test in patients with bleeding gastric or duodenal
      ulcers. PATIENTS AND METHODS: A total of 96 patients with acute peptic ulcer
      bleeding without proton pump inhibitor or antibiotic therapy within the last 14
      days before bleeding were included into the study. During index endoscopy,
      specimens for histological and rapid urease test were obtained from the antrum
      and corpus mucosa of the stomach. Patients were also investigated by the 13C-urea
      breath test. Diagnostic quality parameters were calculated with the histology and
      the 13C-urea breath test as reference and compared with a matched control group
      with uncomplicated ulcers. RESULTS: The sensitivity of the rapid urease test was
      80% and the specificity 100% compared to histology and 13C-urea breath test. The
      negative predictive value was 75%. These values were statistically significantly
      different from those of the control group (sensitivity 96%, specificity 100%,
      negative predictive value 88%). CONCLUSION: The exclusive use of the rapid urease
      test cannot be recommended in patients with peptic ulcer bleeding.

PMID- 12801032
TI  - Contribution of artificial neural networks to the classification and treatment of
      patients with uninvestigated dyspepsia.
AB  - OBJECTIVES: To verify whether symptoms reported by patients with uninvestigated
      dyspepsia might be helpful in either classifying functional from organic
      dyspepsia (1st experiment), or recognising which Helicobacter pylori infected
      patients may benefit from eradication therapy (2nd experiment). METHODS: We
      compared the performance of artificial neural networks and linear discriminant
      analysis in two experiments on a database including socio-demographic features,
      past medical history, alarming symptoms, and symptoms at presentation of 860
      patients with uninvestigated dyspepsia enrolled in a large observational multi
      centre Italian study. RESULTS: In the 1st experiment, the best prediction for
      organic disease was given by the Sine Net model (specificity of 87.6% with 13
      patients misclassified) and the best prediction for functional dyspepsia by the
      FF Bp model (sensitivity of 83.4% with 56 patients misclassified). The highest
      global accuracy of linear discriminant analysis was 65.1%, with 150 patients
      misclassified. In the 2nd experiment, the highest predictive performance was
      provided by the SelfDASn model: all infected patients who became symptom-free
      after successful eradicating treatment were correctly classified, whereas nine
      errors were made in forecasting patients who did not benefit from such a therapy.
      The highest global performance of linear discriminant analysis was 53.2%, with 37
      patients misclassified. CONCLUSIONS: In patients with uninvestigated dyspepsia,
      artificial neural networks might have potential for categorising those affected
      by either organic or functional dyspepsia, as well as for identifying all
      Helicobacter pylori infected dyspeptic patients who will benefit from
      eradication.

PMID- 12801033
TI  - A third-line levofloxacin-based rescue therapy for Helicobacter pylori
      eradication.
AB  - BACKGROUND: Helicobacter pylori infection persists in a considerable proportion
      of patients after both first- and second-line current treatments. A standard
      therapy for re-treatment in such refractory patients is still lacking. This study
      aimed to evaluate the efficacy of a levofloxacin-amoxycillin combination in
      patients who previously failed two or more therapeutic attempts. PATIENTS AND
      METHODS: Consecutive patients with persistent Helicobacter pylori infection were
      enrolled. Bacterial infection was assessed by rapid urease test and histology on
      gastric biopsies at endoscopy. Patients were assigned to receive a 10-day triple
      therapy, comprising rabeprazole 20 mg b.d., levofloxacin 250 mg b.d., and
      amoxycillin 1 g b.d. Four to 6 weeks after therapy, Helicobacter pylori
      eradication was assessed by a further endoscopy or 13C urea breath test. RESULTS:
      Overall, 36 patients were enrolled, but two patients were lost to follow-up.
      Helicobacter pylori was successfully cured in 30 patients, giving an 83.3% (95%
      CI=71.2-95.5) and 88.2% (95% CI=77.4-99) eradication rate at intention-to-treat
      and per protocol analysis, respectively. Compliance was good in all but two
      patients, who discontinued the treatment at 8 and 6 days, respectively, on
      account of glossitis. No major side-effects were reported, whilst 7 (20.1%)
      patients complained of mild side-effects. CONCLUSIONS: This study demonstrates
      that a 10-day levofloxacin-amoxycillin triple therapy is a safe and successful
      third-line therapeutic approach for Helicobacter pylori eradication.

PMID- 12801034
TI  - Common presence of Helicobacter DNA in the gallbladder of patients with gallstone
      diseases and controls.
AB  - BACKGROUND: Several species of Helicobacter colonise the biliary tract of animals
      and cause hepatobiliary diseases. Helicobacter species have also been identified
      in the gallbladder of a high proportion of Chilean patients with gallbladder
      cancer. AIM: To determine the presence of Helicobacter species, particularly
      Helicobacter pylori and Helicobacter bilis, in the gallbladder of patients with
      non-malignant gallbladder diseases and control patients. PATIENTS AND METHODS:
      DNA was extracted from gallbladder samples from 122 consecutive patients
      undergoing cholecystectomy. The presence of Helicobacter genus-specific or
      Helicobacter pylori and Helicobacter bilis species-specific DNA was determined by
      polymerase chain reaction and sequence analysis. The presence of Helicobacter
      pylori-specific immunoglobulin G in the serum (n=84) and bile (n=104) samples was
      determined by enzyme linked immunosorbent assay. RESULTS: Helicobacter DNA was
      detected in 61 (50.0%) gallbladder samples: 29 of 60 (48.3%) patients with
      symptomatic gallstone, six of 10 (60.0%) patients with asymptomatic gallstones,
      11 of 15 (73.3%) patients with other biliary diseases, and 15 of 37 (40.5%)
      control patients, respectively. Among them, 39 samples were positive for
      Helicobacter pylori but none were positive for Helicobacter bilis. Sequence
      analysis of Helicobacter genus-positive samples showed that 56 samples were
      Helicobacter pylori and five were Helicobacter species 'Liver 3' strain. Overall,
      there was no significant difference in the detection rate of Helicobacter DNA or
      the levels of serum and bile Helicobacter pylori-specific immunoglobulin G in the
      various biliary disease groups compared with control patients. Neither was there
      any significant difference in the blood biochemistry and liver function tests
      between patients with positive and negative Helicobacter DNA detection.
      CONCLUSION: Helicobacter species' DNA are commonly present in the gallbladder of
      patients with gallstone diseases and in controls, implying that Helicobacter
      infection alone may not play a significant role in the formation of gallstones.
      However, our results do not exclude the possibility of Helicobacter infection as
      a cofactor in the development of gallstones.

PMID- 12801035
TI  - 5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in
      the guinea-pig gastrointestinal tract.
AB  - BACKGROUND: The dopamine D2 receptor antagonist levosulpiride is a substituted
      benzamide derivative, whose gastrokinetic properties are exploited clinically for
      the management of functional dyspepsia. However, for other benzamide derivatives,
      such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is
      considered the main mechanism leading to gastrointestinal prokinesia. AIMS: To
      assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea
      pig isolated gastrointestinal tract. MATERIALS AND METHODS: Circular muscle
      strips from gastric antrum, and colonic longitudinal muscle strips were used to
      detect electrically stimulated neurogenic contractions. The effect of
      levosulpiride was assessed in the absence and presence of GR125487, a selective 5
      HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with
      5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal
      longitudinal muscle-myenteric plexus preparations. RESULTS: Antral and colonic
      strip contractions were cholinergic/tachykinergic in nature. Micromolar
      concentrations of levosulpiride potentiated submaximal responses, through a
      mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs,
      levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist
      2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine.
      CONCLUSIONS: Our results indicate that levosulpiride acts as a moderate agonist
      at the 5-HT4 receptor. This property, together with antagonism at D2 receptors,
      may contribute to its gastrointestinal prokinetic effect.

PMID- 12801036
TI  - Electrolyte profiles within the ileoanal pouch: measurement by an in vivo
      equilibrium dialysis technique.
AB  - BACKGROUND: Patients with an ileoanal pouch have high rates of fluid and
      electrolyte loss. These improve with pouch adaptation. There is limited
      information concerning secretion and absorption in the stable ileoanal pouch. A
      new method to measure and characterize electrolytes in the ileoanal pouch is
      described. METHODS: Following an in vitro study, nine patients with a stable
      ileoanal pouch had consecutive placement of dialysis bags consisting of a semi
      permeable membrane containing 5 ml of 10% dextran in normal saline into the
      ileoanal pouch. These were left in place for 15, 30, 60, and 120 min. After
      determining that 60 min was the optimal timing for measurement of electrolyte
      concentrations, 12 normal volunteers underwent a similar in vivo dialysis study
      with dialysis bags withdrawn at 60 min. Sodium, chloride, potassium, phosphorus,
      calcium and magnesium concentrations in the dialysis bags were compared between
      the two groups. RESULTS: In the in vitro and in vivo studies, the measured
      electrolytes reached equilibrium within 60 min. Statistically significant
      differences between sodium concentrations (160.9 +/- 30.2 vs. 116.8 +/- 13.8
      mmol/l, respectively) and phosphorus concentrations (6.8 +/- 5.2 vs. 1.8 +/- 0.7
      mg/dl, respectively) at 60 min in ileoanal pouch patients and volunteers were
      found (p<0.001). There were no statistical differences in the other measured
      electrolytes between the two groups. CONCLUSION: An in vivo dialysis technique is
      described for measuring electrolyte concentrations within the ileoanal pouch.
      Differences in sodium and phosphate concentrations may reflect incomplete
      adaptation of the ileoanal pouch, and are a potential explanation for increased
      stool frequency in these patients.

PMID- 12801037
TI  - Prevalence of sexual and physical abuse and its relationship with symptom
      manifestations in patients with chronic organic and functional gastrointestinal
      disorders.
AB  - A history of physical and/or sexual abuse is a frequent occurrence in patients
      referred for chronic gastrointestinal disorders and it may predispose to the
      development of functional gastrointestinal disorders, and multiple medical
      complaints. This study was aimed to determine: (a) prevalence of abuse history in
      Italian patients with chronic gastrointestinal disturbances, and (b) relationship
      between abuse history and clinical manifestations. SUBJECTS AND METHODS:
      Consecutive gastrointestinal out-patients filled in a self-administered
      standardised questionnaire, made up of two separate sections: (1) a medical
      section enquiring on gastrointestinal and extra-gastrointestinal symptoms, and
      (2) a section on abuse enquiring on the presence and type of abuse suffered
      during their lifetime. Associations between number of symptoms and abuse history
      were evaluated using univariate and multivariate logistic models. RESULTS:
      Questionnaires were handed out to 260 patients; 13% of whom did not fill in the
      questionnaires. Functional gastrointestinal disorders were diagnosed in 72.5% of
      patients and organic gastrointestinal diseases in 27.5%. A total of 31% of
      patients with organic gastrointestinal diseases and 32% of those with functional
      gastrointestinal disorders referred to a history of sexual or physical abuse.
      Histories of physical plus sexual abuse, sexual abuse, childhood abuse and female
      gender, were statistically associated with an increased number of
      gastrointestinal and extra-gastrointestinal symptoms irrespective of functional
      or organic disorders, whereas there was no statistical association with physical
      abuse only. Furthermore, diagnosis of functional gastrointestinal disorders was
      associated with a significantly (p<0.001) greater number of gastrointestinal
      symptoms than the diagnosis of organic gastrointestinal diagnosis. A total of 10
      patients met the diagnostic criteria of somatization disorder. Of these, eight
      reported a history of severe physical and sexual abuse that had occurred, in all
      but one, during childhood. CONCLUSIONS: A history of physical and/or sexual abuse
      has a high prevalence in Italian patients with chronic gastrointestinal
      disorders, irrespective of organic or functional diagnosis. Abuse history has no
      relevant role in the pathogenesis of either functional or organic chronic
      gastrointestinal disorders but it can affect their clinical expression
      irrespective of functional or organic diagnosis. Severe physical and sexual abuse
      and childhood abuse were found in patients who met diagnostic criteria for
      somatization disorder, suggesting a role of abuse history in this subset of
      patients.

PMID- 12801038
TI  - Splanchnic haemodynamics in patients with coeliac disease: effects of a gluten
      free diet.
AB  - BACKGROUND: Coeliac disease is characterized by structural and functional changes
      in the small bowel which may also result in haemodynamic changes. AIMS: To
      establish whether splanchnic haemodynamics can be modified by a gluten-free diet.
      PATIENTS: Ten coeliac patients and 10 paired healthy subjects. METHODS: Echo
      Doppler measurements were made of splanchnic vessels both fasting and after a
      standard meal before and after 9 months of a gluten-free diet. RESULTS: In
      comparison to controls, coeliac patients had higher superior mesenteric artery
      blood velocity and flow, with lower resistance indexes and higher portal vein
      velocity and flow, particularly 3 h after a meal. Postprandial hyperaemia was
      reduced and delayed in time. Intrasplenic resistance indexes were also
      significantly lower both fasting and after a meal. After 9 months of a gluten
      free diet, no significant differences were observed between coeliac patients and
      controls, both fasting and after a meal. CONCLUSIONS: Splanchnic haemodynamics is
      significantly changed in coeliac patients, mainly after a meal. On treatment with
      a gluten-free diet, both fasting and postprandial haemodynamics became normal.

PMID- 12801039
TI  - Portal hypertension and portal hypertensive gastropathy in patients with liver
      cirrhosis: a haemodynamic study.
AB  - BACKGROUND/AIM: The relationships between the levels of portal hypertension and
      the morphologic alterations of gastric mucosa in patients with liver cirrhosis-
      generally described as portal hypertensive gastropathy--are poorly defined.
      PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were
      examined by endoscopy and measurement of portal hypertension by hepatic venous
      pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49
      cases; six patients showed gastric antral vascular ectasia always associated with
      gastric lesions described as severe portal hypertensive gastropathy with
      different localizations. Hepatic venous pressure gradient showed severe portal
      hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in
      patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in
      patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04)
      than in those with isolated lesions in body-fundus. No relationship was found
      between hepatic function, as assessed by the Child-Pugh score, and portal
      hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity
      of portal hypertensive gastropathy is related to portal hypertension, but portal
      hypertension is not the sole determinant of the occurrence of endoscopic
      abnormalities of gastric mucosa. The derangement of liver function does not
      appear to play any role in the occurrence of portal hypertensive gastropathy.

PMID- 12801040
TI  - Are metal stents effective for palliation of malignant dysphagia and fistulas?
AB  - BACKGROUND: One of the available treatments for unresectable oesophagogastric
      malignancies is the insertion of metal stents. AIMS: We evaluated prospectively
      147 patients suffering from malignant dysphagia and/or fistula, after inserting a
      self-expandable metal stent. PATIENTS AND METHODS: The study included 147
      patients (87 males, mean age 73 years). Dysphagia before and after stent
      placement was scored. Patients were divided in two groups according to dysphagia
      grade: group A (grade 0, 1) and group B (grades 2, 3, 4). Three types of stents
      were used: the Ultraflex stent (covered and uncovered) and the Flamingo one
      (covered). The total number of self-expandable metal stents placed was 183. A
      total of 92 of them were inserted following the combined endoscopic and
      fluoroscopic approach (42 by injecting lipiodol), while 91 were placed under
      endoscopic control only. Early and late complications were evaluated. RESULTS:
      Mean dysphagia score in group A, 1 day and 1 month after the procedure, was
      slightly reduced from 0.8 to 0.5/0.6 (p=NS), respectively. However, there was a
      statistically significant improvement (p<0.001) of mean dysphagia score in group
      B, from 2.4 initially to 1.1/1.4. Early complications occurred in 37 cases, late
      ones in 51. According to severity, minor complications occurred in 24 patients,
      major in 42, while life-threatening ones in 22. Survival ranged from 1 to 611
      days and 1-week mortality was 9%. Stent-related death occurred in six patients.
      CONCLUSIONS: All kinds of endoscopic methods used for stenting in the present
      study were easy to perform even on an out-patient basis. Insertion of self
      expandable metal stents is effective in patients with dysphagia scores > or = 2.
      It might not clinically improve patients with dysphagia score <2, so selection of
      patients for stenting is essential to avoid unnecessary procedures. Moreover,
      their high cost, high complication rates and low overall survival may improve
      following better selection criteria.

PMID- 12801041
TI  - Abdominal tuberculosis with pancreatic involvement: a case report.
AB  - A case of abdominal tuberculosis with pancreatic involvement is described. A 27
      year-old Italian male, with no known cause of immunodeficiency and with no
      evidence of pulmonary tuberculosis, was admitted to our division because of acute
      pancreatitis. Abdominal imaging revealed a large 'tumour-like' mass in the
      pancreas head compressing the distal choledochous, and multiple adenopathy.
      Histological examination of multiple specimens removed during explorative
      laparotomy revealed granulomas with giant cells, caseous necrosis, and positive
      Ziehl-Neelsen staining. Tissue culture was positive for Mycobacterium
      tuberculosis. Once specific medical treatment was started, the pancreatic damage
      completely resolved.

PMID- 12801042
TI  - The stomach and iron deficiency anaemia: a forgotten link.
AB  - Iron deficiency anaemia is generally considered a sign of occult bleeding from
      the gastrointestinal tract, and standard care therefore includes evaluation of
      the gastrointestinal tract to rule out possible bleeding sites. However, it is
      often overlooked that iron deficiency anaemia may be the result of an imbalance
      between iron loss and iron intake, and may also be due to reduced absorption of
      iron from food, i.e., coeliac disease. The absorption of alimentary iron is not a
      simple process and the stomach plays a major role in this process of iron
      "digestion". This review presents evidence linking iron deficiency anaemia to
      gastric conditions that lead to reduced acid secretion, such as, for example,
      gastric surgery, atrophic body gastritis and Helicobacter pylori gastritis.

PMID- 12801043
TI  - Radiologically inserted gastrostomies: their use in patients with cancer of the
      upper aerodigestive tract.

PMID- 12801044
TI  - Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in
      advanced oesophago-gastric and pancreatic cancer: results of two phase II
      studies.
AB  - Cisplatin is an active palliative chemotherapy agent in advanced upper
      gastrointestinal cancer, but it is associated with significant non-haematological
      toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy
      regimens may reduce these adverse effects. These two phase II studies evaluated
      the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6
      weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3
      weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day
      (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and
      June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago
      gastric study and eight patients in the pancreatic study. Although non
      haematological toxicity was modest, both protocols were closed prematurely
      because of excessive haematological toxicity and frequent treatment delays. The
      overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%,
      respectively. The McarboF combination showed significant activity with an overall
      response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was
      also evident with improvement in symptoms of pain and weight loss in over 79 and
      50% of patients in the oesophago-gastric study and pancreatic study,
      respectively. Median overall survival times were 10.6 and 6.6 months for patients
      with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen
      showed promising activity in advanced upper gastrointestinal cancer, with modest
      non-haematological side-effects. This combination merits further evaluation with
      modification of the dose and schedule of carboplatin and MMC in order to reduce
      the severity of haematological toxicity.

PMID- 12801045
TI  - Relapse patterns after chemo-radiation for carcinoma of the oesophagus.
AB  - AIM: The detailed review of patterns of failure in this report was undertaken to
      identify the continuing obstacles to the successful management of oesophageal
      cancer, and to establish whether there is a case to compare definitive chemo
      radiation (Def-CR) and surgery for patients with squamous cancer in a randomized
      controlled trial. MATERIALS AND METHODS: First and subsequent sites of failure
      were reviewed in 274 patients treated with Def-CR using two cycles of cisplatin,
      infusional fluorouracil and 60 Gy; and 92 patients with limited chemo-radiation
      (CR), using one cycle and 35 Gy, followed by surgery (CR-Surg). All were treated
      on prospective non-randomized trials run by the Trans-Tasman Radiation Oncology
      Group between 1985 and 1999. Failure patterns were analysed using competing risks
      methodology, and pre-treatment variables predicting survival were identified by
      proportional hazards modelling. RESULTS: Site, stage, performance status and
      gender were independently predictive of survival following Def-CR. Local failure
      was evident in 42.3% of patients, but distant failure in isolation occurred in an
      additional 18.1%. Lowest rates of local and distant failure at 5 years (29.9% and
      26%) occurred in patients with squamous cancer (SCC) located in the upper-third,
      whose 5-year survival was also the most favourable (49.2%). Survival was least
      favourable in patients with adenocarcinoma (AC) in the lower two-thirds (18.1%)
      due to higher rates of local (51.5%) and distant (36.1%) failure. Local failure
      occurred in 31.5% of patients undergoing CR-Surg but distant failure in isolation
      was observed in a further 34.7%. Outcomes were least favourable in patients with
      AC of the lower-third in whom 57.7% failed distantly and 5-year survival was
      3.8%. Response to pre-operative chemo-radiation was also strongly predictive of
      outcome. Patients with no residual cancer in the resection specimen had the
      lowest rates of local (0%) and distant (16.7%) failure and the best survival
      (64.9%). Survival in patients with residual cancer in nodes, however, was
      extremely poor (3.5%) with distant failure occurring in 66.7%. CONCLUSION: The
      concurrent administration of chemotherapy with radiotherapy seems to have
      improved loco-regional control and has exposed distant failure as an obstacle to
      further improvements in outcome. Site, histological subtype, gender and response
      to chemo-radiation may predict biological differences in oesophageal cancer (OC)
      that influence outcome. A good case for a randomized comparison between Def-CR
      and CR-Surg in patients with SCC in the lower two-thirds exists.

PMID- 12801046
TI  - A phase I/II study of CHARTWEL with concurrent chemotherapy in locally advanced,
      inoperable carcinoma of the oesophagus.
AB  - AIM: To evaluate the feasibility, efficacy and toxicity of concurrent
      chemotherapy and continuous, hyperfractionated, accelerated radiotherapy weekend
      less (CHARTWEL) in the treatment of locally advanced, inoperable oesophageal
      cancer. METHODS: A prospective study of 19 patients with histologically
      confirmed, locally advanced, inoperable carcinoma of the oesophagus. CHARTWEL was
      prescribed from day 1 to doses of 40.5 Gy (three patients), 42 Gy (five
      patients), 45 Gy (four patients), 46.5 Gy (three patients) and 49.5 Gy (four
      patients). Cisplatin 75 mg/m2 was administered on day 1 of radiotherapy, followed
      by 5-fluorouracil (5-FU) 1000 mg daily for 4 days. RESULTS: All patients
      completed radiotherapy, with two requiring modification of their chemotherapy
      dose. Acute toxicity was acceptable, with no interruptions to treatment. The
      median dysphagia free time was 9.6 months with 38% of patients being dysphagia
      free at 42 months. The median time to locoregional relapse was 13.2 months with
      50% being free at 1 year and 35% at 3.5 years. There was a trend towards greater
      control when the higher doses (45-49.5 Gy) were compared with the lower doses
      (40.5-42 Gy), P = 0.07. The median survival time was 10.7 months with 1- and 2
      year survival rates of 50 and 26%, respectively. Strictures developed in seven
      out of 18 patients (38%), but five were found on biopsy to be due to recurrent
      disease. There was no other long-term toxicity and no treatment-related death
      occurred. CONCLUSIONS: CHARTWEL with concomitant cisplatin/5-FU chemotherapy is a
      feasible treatment option in these patients. It is well tolerated, achieves a
      high rate of local control and effectively palliates the symptoms of dysphagia,
      all with relatively rapid resolution of treatment-related toxicity. The results
      warrant continued dose escalation to 51 Gy.

PMID- 12801047
TI  - The significance of cardiac doses received during chemoradiation of oesophageal
      and gastro-oesophageal junctional cancers.
AB  - AIM: Although radiation-induced cardiotoxicity has been described in patients
      with breast cancer and Hodgkin's disease, the effect of oesophageal radiotherapy
      on the heart has not been evaluated. This study was designed to evaluate the dose
      received by the heart during chemoradiotherapy (CT-RT) for oesophageal cancer, to
      assess its impact on cardiac function, and explore methods of reducing this dose.
      METHODS: Cardiac doses were calculated from dose-volume histograms in 15 patients
      with carcinoma of mid and lower oesophagus undergoing combined technique
      treatment, in whom pre- and post-treatment multigated acquisition scans were
      available. Chemotherapy consisted of cisplatin and 5-fluorouracil with or without
      paclitaxel. The radiotherapy was delivered in two phases to a total dose of 45-50
      Gy in 25 fractions. RESULTS: There was a significant reduction in median ejection
      fraction after CT-RT (63% to 58%, P = 0.003). The median dose received by the
      heart using three-dimensional conformal technique was 27.4 Gy (interquartile
      range 25.8-34.2 Gy). If shielding blocks were not used, as would be the case with
      conventional planning, the median dose would have been 35 Gy (interquartile range
      28.2-37.7 Gy), which is significantly higher (P = 0.002). The use of a three
      field technique throughout treatment also reduced the median cardiac dose from
      27.4 Gy to 22.7 Gy (P = 0.001) and the volume of heart receiving 70% of total
      dose from 63.8% to 25% (P = 0.001). CONCLUSION: This study highlights the
      significant dose of radiation received by the heart during oesophageal CT-RT,
      with consequent reduction in cardiac ejection fraction. Conformal radiotherapy
      reduces cardiac doses received. The cardiac, as well as the pulmonary, side
      effects of CT-RT needs to be borne in mind, especially when using this treatment
      before radical surgery.

PMID- 12801048
TI  - The role of CT scanning in the surveillance of testicular tumours.

PMID- 12801049
TI  - Use of FDG-PET in testicular tumours.

PMID- 12801050
TI  - Multiple relapses of mature teratoma, germinal and non-germ cell cancer in a
      patient treated with chemotherapy for testicular non-seminomatous germ cell
      cancer.

PMID- 12801051
TI  - Combination chemotherapy with docetaxel and irinotecan in metastatic malignant
      melanoma.
AB  - AIM: The aim of the current trial was to assess the efficacy and toxicity of 3
      weekly intravenous docetaxel and irinotecan in the treatment of patients with
      metastatic malignant melanoma. MATERIALS AND METHODS: Sixteen patients with no
      history of previous cytotoxic agents or immunological treatment for advanced
      disease were treated with docetaxel 50 mg/m2 and irinotecan 150 mg/m2
      intravenously over 60 min every 21 days. Prior immunotherapy with interferon and
      chemotherapy for adjuvant therapies were accepted provided there was a minimum 4
      week treatment-free interval. Response evaluation was performed after two cycles.
      RESULTS: None of the patients had chemotherapy-induced tumour response. Eight
      patients achieved stable disease and others had progression of disease. The
      median survival time was 136 days (95% CI: 30.2-241.8), and the 3-month survival
      rate was 62.5%. Patients with stable disease (n = 8) had a longer survival than
      non-responders (P = 0.023, Breslow test). Generally side effects were mild and
      tolerable. Grade III-IV haematological toxicity occurred in approximately 10%.
      Severe emesis, stomatitis and diarrhoea was seen in less than 20% of the
      patients. Alopecia was observed in all patients. CONCLUSION: A 3-weekly
      intravenous docetaxel and irinotecan combination appears to be inactive in the
      treatment of patients with malignant melanoma and has not been recommended.

PMID- 12801052
TI  - Cutaneous basal cell carcinoma of the back metastasizing to the ipsilateral
      latissimus dorsi muscle.
AB  - Metastases from cutaneous basal cell carcinomata are extremely rare phenomena.
      The majority of haematogenous metastases occur (in descending order) in the lung,
      skin and liver. The ratio of lymphogenic to haematogenic metastases is
      approximately 1 to 1. An exceedingly rare case of a metastasis to skeletal muscle
      is presented.

PMID- 12801053
TI  - Adjuvant radiotherapy after conservative surgery for breast cancer: is it always
      necessary?
AB  - Breast irradiation is used to reduce the risk of within-breast recurrence
      following conservative surgery. This review examines factors--particularly
      patient age--that may be used to select patients at low risk of local failure
      where radiotherapy may not be necessary.

PMID- 12801054
TI  - The appropriate rate of breast conserving surgery: an evidence-based estimate.
AB  - PURPOSE: The objective of the present study was to estimate the proportion of
      incident cases of breast cancer that should receive breast conserving surgery
      (BCS), using an evidence-based approach. METHODS: An extensive search of the
      literature was undertaken to identify eligibility criteria for BCS. The
      eligibility criteria for BCS were combined with the information about case mix
      and patient preference to estimate the need for BCS. An epidemiological approach
      was then used to estimate the incidence of each eligibility criterion for BCS in
      a typical North American population of breast cancer patients. The effect of
      sampling error on the estimated appropriate rate of BCS was calculated, and the
      effect of systematic error using alternative sources of information, was
      estimated by sensitivity analysis. RESULTS: The analysis showed that 69.6% of
      breast cancer cases are eligible for BCS, and that 48.0 +/- 6.0% of breast cancer
      patients are both eligible for BCS and prefer it to mastectomy. Based on
      sensitivity analysis, the plausible range of the appropriate rate was 42.1% to
      49.43%. The proportion of breast cancer cases in which BCS was appropriate was
      stage dependent; 63.0 +/- 11.5% in ductal carcinoma in-situ; 57.0 +/- 9.9% in
      stage I; 52.2 +/- 9.4% in stage II, and 27.2 +/- 5.2% in stage III. CONCLUSIONS:
      This model suggests that BCS is appropriate in 48% of all breast cancer patients.
      This information may be useful in auditing surgical practice, and may serve as a
      basis for planning of ancillary services, including radiotherapy.

PMID- 12801055
TI  - Brachytherapy boost to the tumour bed in high risk patients after limited surgery
      for breast cancer.
AB  - The results of treatment for 174 patients at high risk of local recurrence,
      referred for radiotherapy after conservative surgery for early breast cancer, are
      evaluated. Microscopic margin involvement, extensive carcinoma in situ, and
      vascular/lymphatic invasion were the main risk factors for local recurrence.
      Whole-breast irradiation (40 Gy in 15 fractions over 3 weeks) followed with a
      brachytherapy boost (Ir192 wire implant or PDR Ir192) of 25 Gy was applied.
      Median follow-up was 80 months. The actuarial 6-year overall survival rate was
      91% and the within breast recurrence-free survival was 88%. The most common risk
      factor among those recurring within the breast was involved surgical margins (13
      out of 17). Cosmesis was reported to be good or excellent in 79% of cases. In
      patients at high risk for local recurrence, tumour-bed boost with brachytherapy
      can provide satisfactory local control after limited surgery and external
      radiotherapy.

PMID- 12801056
TI  - Reversible life-threatening encephalopathy in the absence of hepatic failure
      following conventional doses of docetaxel.

PMID- 12801057
TI  - Modified Ifosphamide/CarboPlatin/Etoposide.

PMID- 12801058
TI  - Dural metastases in prostate cancer.

PMID- 12801059
TI  - Vinorelbine and ischaemic colitis.

PMID- 12801061
TI  - Surgery versus radiotherapy for muscle invasive bladder cancer?

PMID- 12801060
TI  - Phlebitis due to irinotecan.

PMID- 12801062
TI  - Autologous cancer vaccine: a novel formulation.
AB  - A novel cancer vaccine consisting of fixed autologous cancer tissue-fragments,
      microparticles encapsulating cytokines, and an adjuvant was developed. In a Phase
      I/IIa clinical trial, vaccination to patients after resection of hepatocellular
      carcinoma induced significantly longer time before the first recurrence than that
      in historical control patients operated in the same department (P < 0.05). This
      formulation will be promising against recurrence of many types of human cancers.

PMID- 12801063
TI  - Comparative studies of the cell structures of Mycobacterium leprae and M.
      tuberculosis using the electron microscopy freeze-substitution technique.
AB  - The cell envelope and cytoplasmic architecture of the Mycobacterium leprae Thai
      53 strain were examined using the freeze-substitution technique of electron
      microscopy and compared with those of the M. tuberculosis H37Rv strain. Both
      strains had similarly multilayered envelope architectures composed of an electron
      translucent layer, a peptidoglycan layer and the plasma membrane, from outside to
      inside. A comparison of the structures of these two mycobacteria revealed that
      the M. leprae cell was smaller in size and had a thinner peptidoglycan layer than
      the M. tuberculosis cell. The cell widths measured on electron micrographs were
      0.44 microm for M. tuberculosis and 0.38 microm for M. leprae. The peptidoglycan
      layer of M. leprae was 4-5 nm, while the corresponding layer of M. tuberculosis
      was 10-15 nm.

PMID- 12801064
TI  - Effects of melanin upon susceptibility of Cryptococcus to antifungals.
AB  - Melanin is a recognized virulence factor in Cryptococcus neoformans; several
      pathogenetic mechanisms have been suggested. We studied melanin as an antifungal
      resistance factor. The growth of laccase-active strains of C. neoformans and C.
      albidus in L-DOPA resulted in the production of black pigment. The formal minimal
      inhibitory concentrations (MICs) of amphotericin B and fluconazole were not
      changed by melanization. However, when we examined those wells which contained
      inhibited cells, we found live cells only in wells containing melanized C.
      neoformans. In contrast, melanization did not protect C. albidus from killing by
      amphotericin B. In an amphotericin B time-kill study of C. neoformans,
      significantly more melanized cells than non-melanized survived for the first few
      hours. Fluorescence microscopy and flow cytometry analyses showed that fewer
      melanized cells were stained with the fluorescent dye MitoRed. Incubation of
      MitoRed (the model) or amphotericin B with melanin extracted from C. neoformans
      decreased the free concentrations of these substances. Fluconazole, in contrast,
      was not removed from solution by melanin. This suggests that neoformans
      cryptococcal melanin deposited amphotericin B in the cell wall binds, reducing
      its effective concentrations.

PMID- 12801065
TI  - An effective sporicidal reagent against Bacillus subtilis spores.
AB  - We developed a reagent which showed significant sporicidal activity against
      Bacillus subtilis spores. This reagent was composed of ethylenediaminetetraacetic
      acid, disodium salt (EDTA-2Na), ferric chloride hexahydrate (FeCl3 x 6H2O) and
      ethanol (tentatively designated as the ethanol reagent). The ethanol reagent
      showed pH- and temperature-dependent sporicidal activity. At pH 0.3, its activity
      was almost the same as that of 0.05% sodium hypochlorite at 20 C and was higher
      at 37 C than at 20 C. The activity of the ethanol reagent was similar both with
      and without 10% serum. The ethanol reagent might be applicable for disinfecting
      Bacillus spores.

PMID- 12801067
TI  - Preferential detection of pro-carboxypeptidase R by enzyme-linked immunosorbent
      assay.
AB  - We generated two monoclonal antibodies (mAbs), 2A16 and 10G1, against pro
      carboxypeptidase R (proCPR), also known as thrombin activatable fibrinolysis
      inhibitor (TAFI). By use of these mAbs, we developed a sandwich enzyme-linked
      immunosorbent assay (ELISA) system to detect proCPR. Since the amount of the
      antigen detectable by the ELISA was essentially the same in fresh plasma and
      serum incubated at 37 C for 1 hr, we concluded that the ELISA system detected not
      only proCPR, but also inactivated CPR generated from proCPR. However, an
      appreciable amount of proCPR remained unactivated in serum. For extensive
      activation of proCPR in plasma, thrombin and thrombomodulin complexes (TTM) can
      be used together with CaCl2. Following extensive conversion of proCPR to CPR by T
      TM and CaCl2, converting plasma to serum (T-TM serum), antigenicity became
      undetectable by ELISA. Further analysis revealed that 2A16 reacts only with
      proCPR although 10G1 reacts with proCPR, active CPR and inactivated CPR.
      Therefore, we concluded that the ELISA system preferentially detects proCPR and
      not CPR. Our sandwich ELISA system utilizing 2A16 and 10G1 provides a suitable
      method for detecting proCPR and can be used to determine levels of proCPR in
      plasma samples from patients.

PMID- 12801066
TI  - Cell-mediated fas-based lysis of dendritic cells which are apparently resistant
      to anti-Fas antibody.
AB  - In this report, the controversy concerning the sensitivity of dendritic cells
      (DCs) to Fas-dependent induction of apoptosis was examined using murine DCs.
      Although DCs could not be lysed when exposed to an anti-Fas antibody, Jo2, the
      observed resistance turned out to reflect their lack of the expression of
      Fc(gamma)R necessary for crosslinking the antibody, rather than their intrinsic
      resistance. Thus, at least a fraction of DCs was sensitive to Jo2 in the presence
      of Fc(gamma)R-expressing by-standers. Consistently, a significant fraction of DCs
      was sensitive to Fas-dependent lysis mediated by T cells including the antigen
      specific killing by CD4+ T cells. Both immature (class II MHClow) and mature
      (class II MHChigh) DCs were sensitive to the Fas-based induction of apoptosis.

PMID- 12801068
TI  - Identification of the spotted fever group rickettsiae detected from Haemaphysalis
      longicornis in Korea.
AB  - Seven Haemaphysalis ticks were found positive in PCR assay of gltA gene to detect
      the spotted fever group (SFG) rickettsiae DNA from 100 ticks. The nucleotide
      sequence of 16S rRNA gene was determined from 5 ticks and compared to those of
      other Rickettsia strains. The nucleotide sequence from 4 ticks showed high
      homologies (99.7 to 100%) with that of R. japonica YH, and that from 1 tick (tick
      no. 48) was identical with that of R. rickettsii R, suggesting that SFG
      rickettsiae exists in Korea. This is the first documentation of SFG rickettsiae
      in Korea.

PMID- 12801069
TI  - Probable laboratory contamination of clinical specimens with Leptospira meyeri.
AB  - Leptospira meyeri were isolated from the blood or the pleural effusion cultures
      of four patients at a commercial clinical laboratory. All isolates were identical
      in their 16S rDNA sequences and NotI or SfiI restriction profiles of the
      chromosome DNA on pulsed-field gel electrophoresis. However, intraperitoneal
      inoculation of the isolate (NIID1) failed to kill hamsters and none of the
      patients' sera reacted with L. meyeri strains isolated, indicating leptospiral
      contamination occurred during laboratory investigation.

PMID- 12801070
TI  - Racial/ethnic differences in parental endorsement of barriers to mental health
      services for youth.
AB  - The present study investigated parental endorsement of barriers to care in a
      racially/ethnically diverse, at-risk sample of youth with mental health needs by
      testing the following hypotheses: (1) African American, Asian/Pacific Islander
      American, and Latino youth would have higher levels of unmet need compared to Non
      Hispanic Whites (NHWs); (2) Parents of ethnic minority youth would report a
      greater number of barriers to mental health services for their children than
      would parents of NHWs; (3) The pattern of greater barrier endorsement by parents
      of ethnic minorities compared to parents of NHWs would persist across different
      barrier types; (4) Barrier endorsement would be related to unmet need for mental
      health services. As hypothesized, ethnic minority youth had higher levels of
      unmet need as compared to NHWs. However, despite this finding, parents of ethnic
      minority youth reported fewer barriers than did parents of NHWs, and this pattern
      generally persisted across barrier types. Furthermore, barrier endorsement was
      unrelated to unmet need. Post hoc analyses suggest the influence of cultural
      factors upon barrier endorsement, indicating the importance of taking such
      influences into account in future research on barriers to care.

PMID- 12801071
TI  - Demonstrating translational research for mental health services: an example from
      stigma research.
AB  - In seeking to understand how the goal of providing efficient and effective mental
      health services can best be attained, services researchers have developed
      principles and methods that distinguish it from other research approaches. In
      2000, the National Institute of Mental Health called for translational research
      paradigms that seek to expand the conceptual and methodological base of mental
      health services with knowledge gained from basic behavioral sciences such as
      cognitive, developmental, and social psychology. The goal of this paper is to
      enter the discussion of what is translational research by illustrating a services
      research program of the Chicago Consortium for Stigma Research on mental illness
      stigma. Our research strives to explain the prejudice and discrimination that
      some landlords and employers show toward people with mental illness in terms of
      basic research from social psychology and contextual sociology. We end the paper
      with a discussion of the implications of this research approach for the very
      practical issues of trying to change mental illness stigma.

PMID- 12801072
TI  - Reliability of the Wraparound Observation Form--Second Version: an instrument
      designed to assess the fidelity of the wraparound approach.
AB  - The push to rapidly implement the wraparound approach for families of children
      with serious emotional disturbance (SED) has resulted in a number of service
      models that may or may not be in accordance with its theoretical foundation.
      Given the number of wraparound programs being implemented nationwide, the need to
      develop instruments that can measure the fidelity of wraparound services in a
      reliable manner should not be ignored. The purpose of this study was to examine
      the interobserver agreement of the Wraparound Observation Form--Second Version
      (WOF-2), an observation system designed to assess the fidelity of wraparound
      services. Observations were conducted across 30 family planning meetings where
      wraparound services were provided. The mean percentage agreement across the 48
      items was 96.7% (range 83.3-100%) and the average kappa statistic was 0.886
      (range = 0.318-1.0). On the basis of these results, the WOF-2 appears to be a
      reliable instrument for assessing the delivery of wraparound services.

PMID- 12801073
TI  - An instrument to assess competencies of providers treating severe mental illness.
AB  - One approach to improving the quality of care for severe mental illnesses (SMI)
      such as schizophrenia is through the improvement of provider competencies; the
      attitudes, knowledge, and skills needed to deliver high-quality care. This paper
      describes a new instrument designed to measure such a set of competencies. A
      total of 341 providers of services to clients with SMI at 38 clinics within 5
      publicly financed treatment organizations in 2 western states were asked to
      complete a paper-and-pencil survey including the new Competency Assessment
      Instrument (CAI: 15 scales, each assessing a particular provider competency), and
      additional measures used to establish validity (Recovery Attitude Questionnaire-
      7, Client Optimism Scale). Seventy-nine percent (N = 269) responded at baseline,
      83% (N = 282) responded at 2 weeks. Ninety-seven percent of baseline respondents
      completed the survey at 2 weeks. Most CAI scales have good internal consistency
      (Cronbach's alphas = .52-.93), test-retest reliability (scales ranged from .42 to
      .78), and validity, and should be useful in efforts to improve care.

PMID- 12801074
TI  - Impact of a primary care quality improvement intervention on use of psychotherapy
      for depression.
AB  - We examine the impact of the two Partners in Care (PIC) primary care quality
      improvement (QI) interventions on counseling services. The QI interventions aimed
      to increase service use, and thereby improve outcomes, and have been shown to
      indeed improve patient outcomes (e.g., K. B. Wells et al., 2000). But whether or
      not use of counseling services actually increased has not yet been examined. The
      QI interventions contained many overlapping elements; however, QI-Therapy
      emphasized cognitive-behavioral therapy, and QI-Meds emphasized medications and
      case management. QI-Therapy patients used more counseling than UC patients at 6
      months, though increases were modest. Some treatment effects persisted until 12
      months, but not beyond. QI-Therapy and QI-Meds patients reported more treatment
      overall (therapy or medication) than UC patients at 6 months, and this effect
      persisted in the QI-Meds clinics until 12 months. Treatment effects were more
      pronounced among those most in need. Despite high rates of referral to
      psychotherapy within the QI-Therapy clinics (81%), only a minority of patients
      actually attended a psychotherapy session within the study (30%). We discuss the
      uptake of therapy in this study as a way to inform future efforts at QI.

PMID- 12801075
TI  - Effects of stachyose on performance, diarrhoea incidence and intestinal bacteria
      in weanling pigs.
AB  - A three-week trial was conducted to evaluate the effects of the oligosaccharide
      stachyose on performance, diarrhoea incidence and intestinal bacterial
      populations in weaned pigs (7.96 +/- 0.2kg). A total of 144 crossbred (Landrace x
      Large White x Duroc) pigs weaned at 28 days were allotted to one of four
      treatments with six pens per treatment and six pigs per pen. The experimental
      diets were based on maize, dried whey and whole-fat milk and were supplemented
      with 0, 1 or 2% stachyose. A fourth diet contained no milk but instead contained
      20% soybean meal to provide 0.78% stachyose and 0.21% raffinose. Inclusion of 1
      or 2% stachyose in the diet depressed growth compared with pigs fed the control
      diet. Pigs fed the soybean meal diet gained weight at a rate similar to pigs fed
      the diet containing 1% added stachyose. Diarrhoea incidence was highest for pigs
      fed the soybean meal diet and lowest for pigs fed the control diet, with pigs fed
      the diets containing stachyose being intermediate. Pigs fed 1% stachyose had more
      lactobacilli in the ileum as well as more bifidobacteria in the caecum and colon
      than control pigs. They also had fewer enterobacteria in the colon. In contrast,
      pigs fed the diet containing 2% stachyose had fewer lactobacilli and
      bifidobacteria in the jejunum, ileum and caecum than did control pigs. Volatile
      fatty acids in the ileum, caecum and colon were highest for pigs fed 1% stachyose
      and lowest for pigs fed 2% stachyose. Volatile fatty acid concentrations were not
      significantly different between pigs fed the soybean meal diet and those fed the
      control. The overall results of this experiment indicate that the oligosaccharide
      stachyose had a negative effect on pig performance and its presence may partially
      explain the poorer performance observed when soybean meal is used as the sole
      source of supplemental protein in cereal-based diets fed to weaned pigs.

PMID- 12801076
TI  - Effect of vitamin E supplementation and partial substitution of poly- with mono
      unsaturated fatty acids in pig diets on muscle, and microsome extract alpha
      tocopherol concentration and lipid oxidation.
AB  - The experiment was organized in a 3 x 2 factorial arrangement with three dietary
      fat blends and a basal (20 mg kg(-1) diet) or supplemented (220 mg kg(-1)) level
      of alpha-tocopheryl acetate. Dietary vitamin E and monounsaturated to
      polyunsaturated fatty acid ratio (dietary MUFA/PUFA) affected muscle alpha
      tocopherol concentration (alpha-tocopherol [log microg g(-1)] = 0.18 (+/- 0.105)
      + 0.0034 (+/- 0.0003) x dietary alpha-tocopherol [mg kg(-1) diet] (P < 0.0001) +
      0.39 (+/- 0.122) x dietary MUFA/PUFA (P < 0.0036)). An interaction between
      dietary alpha-tocopherol and dietary MUFA/PUFA exists for microsome alpha
      tocopherol concentration (alpha-tocopherol [log microg g(-1)] = 1.14 ( +/- 0.169)
      (P < 0.0001) + 0.0056 ( +/- 0.00099) x dietary alpha-tocopherol [mg kg(-1) diet]
      (P <0.0001) + 0.54 (+/- 0.206) x dietary MUFA/PUFA (P < 0.0131) - 0.0033 (+/-
      0.0011) x dietary alpha-tocopherol [mg kg(-1))] x dietary MUFA/PUFA (P <
      0.0067)), and hexanal concentration in meat (hexanal [ng x g(-1)] = 14807.9 (+/-
      1489.8)- 28.8 (+/- 10.6) dietary alpha-tocopherol [mg x kg(-1)] (P < 0.01) -
      8436.6 (+/- 1701.6) x dietary MUFA/PUFA (P < 0.001) + 24.0 (+/- 11.22) x dietary
      alpha-tocopherol-dietary MUFA/ PUFA (P < 0.0416)). It is concluded that partial
      substitution of dietary PUFA with MUFA lead to an increase in the concentration
      of alpha-tocopherol in muscle and microsome extracts. An interaction between
      dietary alpha-tocopherol and fatty acids exists, in which at low level of dietary
      vitamin E inclusion, a low MUFA/ PUFA ratio leads to a reduction in the
      concentration of alpha-tocopherol in microsome extracts and a concentration of
      hexanal in meat above the expected values.

PMID- 12801077
TI  - Effects of dietary supplemental L-carnitine and ascorbic acid on performance,
      carcass composition and plasma L-carnitine concentration of broiler chicks reared
      under different temperature.
AB  - The present study was initiated to determine whether dietary supplemental L
      carnitine and ascorbic acid affect growth performance, carcass yield and
      composition, abdominal fat and plasma L-carnitine concentration of broiler chicks
      reared under normal and high temperature. During the experiment, two temperature
      regimes were employed in two experimental rooms, which were identical but
      different in environmental temperature. The regimes were thermoneutral (20-22
      degrees C for 24 h) or recycling hot (34-36 degrees C for 8 h and 20-22 degrees C
      for 16 h). One-day-old broiler chicks (ROSS) were used in the experiment. A 2 x 2
      x 2 factorial arrangement was employed with two levels (0 and 50 mg/kg) of
      supplemental L-carnitine and two levels (0 or 500 mg/kg) of supplemental ascorbic
      acid in drinking water under thermoneutral or high temperature regimes. Body
      weight gain was affected by high temperature. However, body weight gain was
      significantly improved in animals receiving supplemental L-carnitine, ascorbic
      acid or L-carnitine + ascorbic acid compared to animals receiving unsupplemented
      diet under high temperature. On the other hand, supplemental L-carnitine or L
      carnitine + ascorbic acid reduced body weight gain under thermoneutral condition.
      Supplemental ascorbic acid significantly improved feed conversion efficiency, the
      improvement was relatively greater under high temperature. The L-carnitine
      content in the plasma was higher in the groups receiving supplemental L-carnitine
      and ascorbic acid under high temperature, while broilers fed supplemental L
      carnitine and ascorbic acid had a decreased level of plasma L-carnitine
      concentration under normal temperature. It is concluded that dietary supplemental
      L-carnitine or L-carnitine + ascorbic acid may have positive effects on body
      weight gain, carcass weight under high temperature conditions.

PMID- 12801078
TI  - Performance, carcass characteristics, meat quality and plasma constituents of
      meat type drakes fed diets containing different levels of lysine with or without
      a microbial phytase.
AB  - This experiment was conducted to study growth performance, carcass
      characteristics, meat quality and plasma constituents of Campbell drakes fed
      diets containing different levels of lysine with or without a microbial phytase.
      Basal vegetable duck all-mash diets were fed during the growing (1-35 d of age),
      and finishing period (36-56 d of age) and were formulated to contain 0.90% and
      0.73% lysine (negative control), respectively. These diets were supplemented or
      not with L-lysine HCl, which resulted in a dietary lysine level of 0.90, 0.95,
      1.01 and 1.06% and 0.73, 0.80, 0.87 and 0.94%, during the growing and finishing
      period, respectively. Furthermore, the diets were fed with or without 600 FTU
      phytase (Natuphos) except for those containing 1.06 and 0.94% lysine during the
      growing and finishing period, respectively (positive control). A lysine level of
      1.01/0.87% in the growing/finishing diet significantly increased BWG and improved
      FCR of drakes by 2.1 and 1.8%, respectively. Phytase significantly increased BWG
      by 2.1% and 3.5% after feeding the basal diet and 1.01/0.87% lysine,
      respectively. Also, FCR was significantly improved by 2.2 and 1.8% of groups fed
      0.95/0.80, and 1.01/0.87% lysine, respectively. Phytase as an independent
      variable increased BWG by 1.8, and improved FCR by 1.0%. Lysine and/or phytase
      did not affect carcass yield, and meat quality treats as well as plasma
      constituents of drakes. However, lysine level at 0.95/0.80% and 1.01/0.87%
      significantly decreased abdominal fat deposition compared to either the negative
      or the positive control. In conclusion, a lysine level of 1.01/0.87% in the
      growing/finishing diets for drakes is adequate. After phytase supplementation of
      the basal diet the BWG at a lysine level of 0.90/0.73% were similar to the
      positive control (1.06/0.94% lysine). However, the best FCR was obtained after
      feeding diets containing 1.01/0.87% lysine supplemented with phytase.

PMID- 12801079
TI  - The combined use of whole Cuphea seeds containing medium chain fatty acids and an
      exogenous lipase in piglet nutrition.
AB  - In search for an alternative for nutritional antimicrobials in piglet feeding,
      the effects of adding whole Cuphea seeds, as a natural source of medium chain
      fatty acids (MCFA), with known antimicrobial effects, and an exogenous lipase to
      a weaner diet were studied. The foregut flora, the gut morphology, some digestive
      parameters and the zootechnical performance of weaned piglets were investigated.
      Thirty newly weaned piglets, initial weight 7.0 +/- 0.4 kg, were divided
      according to litter, sex and weight in two groups (control diet; Cuphea + lipase
      diet). The Cuphea seeds (lanceolata and ignea) (50 g kg(-1)) were substituted for
      soybean oil (15 g kg(-1)), Alphacell (25 g kg(-1)) and soy protein isolate (10 g
      kg(-1)) in the control diet. Also 500 mg kg(-1) microbial lipase was added to the
      Cuphea diet. The piglets were weighted individually on days 0, 3. 7, 14 and 16.
      Feed intake was recorded per pen during days 0 to 3, 3 to 7, 7 to 14 and 14 to
      16. On day 7 five piglets of each experimental group were euthanized for counting
      the gastric and small intestinal gut flora and for gut morphology at two sites of
      the small intestine (proximal, distal). The results indicate a trend towards
      improved performances parameters by feeding Cuphea + lipase. The enzymic released
      MCFA (1.7 g kg(-1) fresh gastric contents) tended to decrease the number of
      Coliforms in the proximal small intestine, but increased the number in the
      stomach and distal small intestine. With Culphea, the number of Streptococci was
      significantly lower in small intestine, but not in the stomach, while the number
      of Lactobacilli was significantly lower in the distal small intestine and tended
      to be lower in the stomach and proximal small intestine. No differences between
      the diets were noted for the total anaerobic microbial load in the stomach or in
      the gut. Feeding Cuphea + lipase resulted in a significantly greater villus
      height (distal small intestine) and a lesser crypt depth (proximal and distal
      small intestine) and greater villus/crypt ratio depth (proximal and distal small
      intestine). The intra-epithelial lymphocyte (IEL) counts per 100 enterocytes were
      significantly decreased in the proximal small intestine and tended to decrease in
      the distal small intestine by feeding the Cuphea + lipase diet. Both phenomena
      are indicative for a more healthy and better functional state of the mucosa.
      Present results are in line with foregoing research, showing that manipulation of
      the gut ecosystem by the enzymic in situ released MCFA in the stomach and foregut
      can result in improved performances of the piglets, which makes the concept a
      potential alternative for in-feed nutritional antibiotics.

PMID- 12801080
TI  - Effects of Moringa oleifera seed extract on rumen fermentation in vitro.
AB  - Moringa oleifera is a pantropical tree of the family Moringaceae. A previously
      undescribed property of an aqueous extract from the seeds of this plant is the
      modulation of ruminal fermentation patterns, especially protein degradation, as
      demonstrated in a short-term batch incubation system. Gas, short chain fatty
      acids (SCFA) and cellulolytic enzyme activities were determined as general
      fermentation parameters. A dot blot assay able to directly detect true protein in
      rumen fluid samples was used to quantify protein degradation. For complex
      substrates the interpretation of protein degradation profiles was amended by
      polyacrylamide gel electrophoresis (PAGE) of the samples. When incubated with
      pure carbohydrates at a concentration of 1 mg ml(-1), the extract reduced
      microbial degradation of the model protein, bovine serum albumin (BSA), such that
      its concentration was at least 40% above the control after 12 h of incubation.
      Total protein degradation was thus delayed by approximately 9 h. When fermented
      along with wheat straw, leaf protein (Rubisco) was almost entirely protected
      during 12 h of fermentation. The degradation of soy proteins was retarded by at
      least 4-6 h, depending on the protein band. There were strong side effects on the
      fermentation of pure cellulose (SCFA yield-60% after 12 h), whereas cellobiose
      and starch fermentation were less affected (-18 and -8%, respectively). When the
      complex substrates were fermented, SCFA yield was reduced by approximately 30%
      after 12 h. In our work we clearly demonstrate the efficacy of the new substance,
      which is neither a tannin nor a saponin, in an in vitro system, using pure as
      well as complex substrates. The properties shown in vitro for the crude extract
      suggest that it could have a positive effect on the protein metabolism of
      ruminants under intensive management and that negative side effects can be
      overcome by an optimized dosage. If the chemical nature of the active substance
      and its mechanism of action can be clarified, it may provide an alternative to
      replace critical synthetic feed additives (such as antibiotics) for high yielding
      dairy cows.

PMID- 12801081
TI  - A broad spectrum of mitochondrial shapes in active secretory cells of the parotid
      gland of the dromedary (Camelus ferus f. dom.).

PMID- 12801082
TI  - Appearance of erythrocyte-like globules in the mouse visceral yolk sac endodermal
      cells on embryonic day 12, with special reference to blood islands.
AB  - The mouse visceral yolk sac (VYS) is widely known to play an important role as
      erythropoietic tissue during embryonic periods. Mouse VYS from embryonic days 9
      to 12 was examined by light microscopy, electron microscopy and histochemical
      analysis with benzidine to detect the presence of hemoglobin with special
      reference to the development of VYS, the disappearance of the blood islands in
      VYS, and the appearance of a novel structure in the form of erythrocyte-like
      globules in VYS endodermal cells. The villous appearance of VYS became
      complicated by the development of VYS endodermal cells. The blood islands
      positive for the benzidine reaction were light microscopically detected on
      embryonic days 9, 10, and 11. They disappeared on embryonic day 12, however.
      Erythrocyte-like globules positive for the benzidine reaction were not observed
      in VYS endodermal cells on embryonic days 9, 10, and 11, but then appeared on
      embryonic day 12, by light and electron microscopy. Erythrocyte-like globules in
      VYS endodermal cells, which appear after the disappearance of blood islands in
      VYS, may participate in erythropoiesis during embryonic development.

PMID- 12801083
TI  - Scanning electron microscopic findings in respiratory nasal mucosa following
      cigarette smoke exposure in rats.
AB  - In the present study, the respiratory epithelium of the nasal mucosa of rats that
      had been exposed to cigarette smoke was examined by scanning electron microscope
      (SEM). Some significant morphological changes such as increased mucociliar
      activity, compound cilia, disorientation, short cilia and protrusive Goblet cells
      were observed.

PMID- 12801084
TI  - Centroacinar and intercalated duct cells as potential precursors of pancreatic
      endocrine cells in rats treated with streptozotocin.
AB  - The present study examined the possibility for regeneration of pancreatic
      endocrine cells from centroacinar (CA) and intercalated duct (ICD) cells in rat
      pancreas after 5 days of continuous streptozotocin (STZ) administration. Nine
      rats were divided into 3 experimental groups: 1) Control group, 2) Short term
      recovery group; three days after STZ administration (STZ 3), and 3) Long term
      recovery group; ten days post-STZ administration (STZ 10). The CA and ICD cells
      in the STZ 3 group had swollen cytoplasm, and sometimes contained a vesicle
      within the core. An insulin positive signal was detected in and around the CA and
      ICD cells. In the STZ 3 group, cytokeratin 20 signals were co-localized with
      insulin signals in both CA and ICD cells. Electron microscopically, endocrine
      cells and small pancreatic islets were in close contact with CA and ICD cells.
      Systemic biophysical serum data reflected these immunohistological results. The
      present results suggest that CA and ICD cells are involved in the regeneration of
      pancreatic B cells in rats following a lesion produced by five consecutive days
      of STZ administration.

PMID- 12801085
TI  - Structural and ultrastructural aspects of the pericardial sac in some sea water
      teleosts.
AB  - Generally, in fishes the parietal pericardium is considered to be a semi-rigid
      structure. It is widely known that the entire parietal pericardium in fish, in
      contrast to that of higher vertebrates, is fixed to the body wall which consists
      mainly of skeletal muscle. This structural arrangement could explain the low end
      systolic intrapericardial pressure in fishes. The morphology of the parietal
      pericardium of 11 sea-water teleosts, either free or breeding, coming from
      various areas of the southern Italy was studied. Macroscopical evaluation, but
      even more, histological and ultrastructural studies, showed some differences
      among the hearts of the examined subjects, more pronounced in the European hake
      (Merluccius merluccius, L.), in which a true pericardial sac was demonstrated,
      well differentiated and distinguishable from the other structures, in contrast to
      the observations in other subjects. The pericardial connective tissue showed no
      continuity with that of the surrounding structures, mainly skeletal muscle. This
      difference could be retraced to the well-known pattern of life and, therefore, to
      other individual as well as evolutionary factors in comparison with other
      teleosteans examined.

PMID- 12801086
TI  - Histochemical analysis of glycoconjugates in the ceruminous glands of the North
      American raccoon (Procyon lotor).
AB  - The distribution and selectivities of glycoconjugates in the ceruminous glands of
      the North American raccoon (Procyon lotor) were studied by light and electron
      microscopic histochemical methods, particularly lectin histochemistry. In the
      modified apocrine glands present, the apocrine secretion mode was combined with
      exocytosis, whereby the secretory epithelium and the luminal secretion of the
      ceruminous glands exhibited considerable amounts of complex carbohydrates with
      various terminal sugars (alpha-D-mannose, beta-D-galactose, alpha-L-fucose, alpha
      N-acetyl-galactosamine, beta-N-acetyl-D-glucosamine, N-acetyl-neuraminic acid).
      Alpha-L-fucose and N-acetyl-neuraminic acid were distinctly prominent in
      secretory granules or within the free surface coat of the plasma membrane of the
      glandular cells, as well as in the luminal secretion. Several free sugars (alpha
      D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine) were
      also detectable in the secretion of associated sebaceous glands. The ceruminous
      gland secretion may control viscoelasticity and/or bacterial degradation of the
      glandular secretion mixture to improve the protection of the external auditory
      canal against physical damage or microbial contamination.

PMID- 12801087
TI  - Rescue of rat spinal motoneurons from avulsion-induced cell death by intrathecal
      administration of IGF-I and Cerebrolysin.
AB  - Ventral root avulsion results in the loss of motoneurons in the corresponding
      spinal cord segment. In the present experiments we have tested effects of insulin
      like growth factor-I (IGF-I) and Cerebrolysin on survival of avulsed motoneurons
      after their chronic intrathecal administration in the adult rats. We have found
      that avulsion of the C5 ventral roots results in significant loss of motoneurons
      in the same spinal cord segment due mainly to apoptosis. In comparison to the
      untreated control rats, the amount of motoneuron survival in avulsed ventral horn
      was significantly higher after 4 weeks intrathecal administration of IGF-I or
      Cerebrolysin. No significant differences were observed between effects of IGF-I
      and Cerebrolysin in our experimental model. The results suggest that both IGF-I
      and Cerebrolysin can reduce avulsion-induced loss of adult rat motoneurons.

PMID- 12801088
TI  - Tooth development in Ambystoma mexicanum: phosphatase activities, calcium
      accumulation and cell proliferation in the tooth-forming tissues.
AB  - Prerequisites of tooth formation, cell proliferation in the tooth-forming
      tissues, calcium accumulation and the enzymatic activities of alkaline (ALP) and
      acid phosphatases (ACP) were investigated by immunohistochemical and
      histochemical methods in various developmental stages of the Mexican Axolotl,
      Ambystoma mexicanum. During the growth of replacement teeth, the tooth-forming
      tissues continually recruit cells from the surrounding regions. The basal layer
      of the oral epithelium, the dental lamina and sometimes even the outer enamel
      epithelium provide cells for the differentiated inner enamel epithelium, in which
      the active ameloblasts are localized. The differentiating odontoblasts are
      derived from proliferating cells situated basally to the replacement teeth in the
      mesenchymal tissue. When differentiation has started and the cells have become
      functional, proliferative activity can no longer be observed. Calcium is
      accumulated close to the site of mineralization in the inner enamel epithelium
      and in the odontoblasts as it is in mammals, elasmobranchii and teleostei. The
      activities of ACP and ALP related to the mineralization of the replacement teeth
      are separated spatially and not sequentially as they are in mammals. However, the
      results indicate a similar function of these enzymatic components in relation to
      tooth formation and maturation of mineral deposition. Most of the substantial
      processes related to tooth formation reported from other vertebrates occur in a
      manner similar to that in Ambystoma mexicanum, but there also seem to be basic
      mechanisms present that are realised in a unique way in this urodele.

PMID- 12801089
TI  - [Problems in the development of a comprehensive three-dimensional databank of the
      human skull for the preoperative preparation of an exact implant for the
      treatment of bone defects].
AB  - Various human skulls were scanned with a laser scanner. Impressive Landmarks of
      the skull were determined and tested to be comparable stored in a uniform
      coordinate system for subsequent 3-d reconstruction. The Rhinion, the Nasion, the
      Spina nasalis anterior, the Prosthion, and the Opisthokranion were found to be
      very qualified for the adjustment in the median plane. The frontal plane was
      defined by the Rhinion and the Spina nasalis anterior. The Mastoidealia, the
      Zygomaxillaria and the Orbitalia were used to align the skull in the horizontal
      plane. The qualification of the database as a fundamental part for the comparison
      of human skulls and for the discovery of similarities to patient skulls with bone
      defects is demonstrated by means of 2 clinical cases. A subsequent result is the
      application to manufacture fitting implants of biocompatible materials for
      covering huge side-overlapping bone destructions.

PMID- 12801090
TI  - The skull structure of six species of Mesoamerican plethodontid salamanders
      (Amphibia, Urodela).
AB  - The skulls of six species of plethodontid salamanders of the genus Bolitoglossa
      from Costa Rica and Panama, Bolitoglossa colonnea, B. dofleini, B. lignicolor, B.
      marmorea, B. schizodactyla and B. striatula are comparatively analysed. All
      species are terrestrial or slightly arboreal and show no life-mode-dependent
      skull characteristics. Heads cleared by transparent preparation and stained in
      toto were used for examination of the skull structure and paraffin sections of
      the gonads were prepared to confirm sexual maturity of each individual. Focussing
      on the size of the premaxillary pars dentalis, the degree of fusion of the
      processus dorsales praemaxillares and the presence or absence of the paired
      prefrontals we state that B. dofleini and B. striatula possess more ancestral
      characteristics, B. marmorea is situated in an intermediate position and B.
      colonnea, B. lignicolor and B. schizodactyla show more advanced characteristics.

PMID- 12801091
TI  - Simultaneous aberrant left and right gastric veins draining directly into the
      liver.
AB  - Aberrant gastric veins draining directly into the liver are rare variations of
      the portal vein system. We report on an autopsy in which both right and left
      gastric veins drained directly into the liver without joining the portal vein.
      Although the left gastric artery adopted a standard disposition, the left gastric
      vein was indeed found to ascend from the lesser curvature through the upper part
      of the lesser omentum. After receiving branches from the gastroesophageal
      junction, it directly entered the left part of the porta hepatis. The right
      gastric vein ascended from the lesser gastric curvature along and in front of the
      right aspect of the common bile duct without ending in the portal vein. It
      crossed in front of the common hepatic duct and directly entered the porta
      hepatis. Careful dissection within the liver parenchyma showed that both gastric
      veins ended in the intra-hepatic part of the left branch of the portal vein.
      Although aberrant gastric veins are known variations of the portal vein system,
      the conjunction of both right and left gastric vein has never been reported. It
      highlights the possibility that the venous drainage of the gastric lesser
      curvature may be totally independent of the main portal vein.

PMID- 12801092
TI  - Anatomical and behavioural asymmetries in right and left handers from India.
AB  - A biometric study of the right and left limb size and functional-behavioural
      measures, such as, strength of the hand and the foot, foot-eye-ear preferences,
      asymmetries in visual acuity and audiometry, asymmetries in taste and smell
      perceptions was made in a sample of Indian students to find out the
      interrelationships between the above parameters. Healthy adult male (n = 42),
      females (n = 45) right handers, and, male (n = 21), female (n = 20) left handers
      were studied. In each, 8 measurements of each of the limbs were taken, and the
      strength of the hands and feet determined. Hand and foot preferences were
      determined through 11 and 9 tasks respectively. Dominance in the eye, ear, taste
      and smell were ascertained by various tests. Right or left handedness and right
      footedness were clearly discernible but left footedness was indistinct. Right
      handedness was associated with dominant right upper limb and left handedness was
      associated with dominant left upper limb. Only right handers showed a dominant
      corresponding lower limb. Eyedness was related to handedness in males. Earedness
      and taste were associated with handedness in females. Smell had no relationship
      with handedness in both sexes. There was no interrelationship between handedness,
      footedness, eyedness, earedness, taste and smell.

PMID- 12801093
TI  - A study on the effect of inhalative formaldehyde exposure on water labyrinth test
      performance in rats.
AB  - We investigated the effects of repeated inhalative exposure to several
      formaldehyde concentrations (2 hours/day, 10 consecutive days) on the behavior of
      adult male and female LEW.1K rats during a period in which they learned to
      perform a water labyrinth task. We also examined the effects on the histology of
      some organ tissues. While the controls needed increasingly shorter swimming
      periods to complete the water labyrinth test and made fewer errors with advancing
      trial duration, such progress could not be observed in the learning behavior of
      the exposed animals. They took significantly longer swimming periods to reach the
      finish and made significantly more errors in comparison to the controls. The
      statistical comparison between the collected data in the formaldehyde exposed
      male and female rats reveals that females in general reached the end point of the
      swimming labyrinth in significantly less time. On some trial days, however, they
      made more mistakes than males. In the highest concentration group, no gender
      differences were evident in the frequency of errors. The histological examination
      revealed no pathological changes attributable to formaldehyde exposure. Since the
      water labyrinth test is used to investigate changes in memory and learning
      behavior in animals, we conclude that under investigational conditions,
      formaldehyde affects the learning behavior and the memory of male and female
      rats.

PMID- 12801094
TI  - Comparative morphology of the muscles of mastication in the giant panda and the
      Asiatic black bear.
AB  - The morphological differences in the muscles of mastication between the giant
      panda (Ailuropoda melanoleuca) and the Asiatic black bear (Ursus thibetanus) were
      sought to confirm the adaptational strategy of these muscles in the giant panda.
      We measured some skull characteristics and weighed the muscles of mastication,
      and macroscopically observed the muscles of mastication in the two species. The
      noticeable differences between the two species are classified as follows: (1) The
      size ratio of the zygomatic width was much larger in the giant panda than in the
      Asiatic black bear. (2) The weight ratio of the two pterygoid muscles was also
      much larger in the giant panda than in the Asiatic black bear. (3) The lateral
      slips of the temporal muscles are thicker and stronger in the Asiatic black bear
      than in the giant panda. (4) The deep layer of the masseter muscle was
      rostrocaudally divided, and a complicated running of tendons is observed in the
      giant panda. (5) The two pterygoid muscles were much larger and well-developed in
      the giant panda than in the Asiatic black bear. The points (1) and (4) may be
      related to the generation of the force necessary to chew the bamboo in the giant
      panda. We thought that the large mass of the masseter and temporal muscles are
      needed in this species. In the points of (2) and (5), the two pterygoid muscles
      were obviously different in form and weight ratio between the two species. We
      suggest that the two pterygoid muscles may act as an additional force generator
      to dorsoventrally press and crush bamboo stems.

PMID- 12801095
TI  - Application of microscopic fungi isolated from polluted industrial areas for
      polycyclic aromatic hydrocarbons and pentachlorophenol reduction.
AB  - The growth abilities of fifteen fungal strains isolated from contaminated areas,
      in the presence of xenobiotics compounds mixture (overworked cutting fluid, crude
      and waste oil) were examined. Strains with the richest growth were chosen for
      anthracene, phenanthrene and pentachlorophenol biodegradation in Sabouraud medium
      (with initial xenobiotic concentration 250 mg/l in cultures with polycyclic
      aromatic hydrocarbons and 10 mg/l for the chlorinated substrate). Strains IM 1063
      and IM 6325 were able to attack phenanthrene forming its derivative 9
      phenanthrenol with the yields 5.22 mg/l and 2.82 mg/l, respectively. Strain IM
      1063 and IM 6325 transformed pentachlorophenol to an intermediate compound-
      pentachloromethoxybenzene. Final content of pentachloromethoxybenzene reached
      3.46 mg/l and 3.2 mg/l, respectively. Strain IM 6203 (contrary to other strains)
      released an intermediate product of pentachlorophenol metabolism--2,3,5,6
      tetrachlorohydroquinone (8.73 mg/l substrate remaining and 1.2 mg/l 2,3,5,6
      tetrachlorohydroquinone forming). The IM 6203 strain was identified as Mucor
      ramosissimus. The chlorinated pesticide degradation by M. ramosissimus was
      improved significantly on a medium with overworked oil. Only 8.3% of
      pentachlorophenol and 4.3% of 2,3,5,6-tetrachlorohydroquinone in relation to the
      introduced substrate (10 mg/l) were found, after 7 days of incubation. The growth
      of M. ramosissimus on medium with overworked oil in pentachlorophenol presence
      was associated with oil emulgation, which enhanced fungal growth and the
      pesticide degradation.

PMID- 12801096
TI  - Biofiltration of isopropyl alcohol by a trickle-bed air biofilter.
AB  - The performance of trickle-bed air biofilter (TBAB) for the removal of isopropyl
      alcohol (IPA) was evaluated in concentrations varying from 100 to 500 ppmv and at
      empty-bed residence time (EBRT) varying from 20 to 90 s. Nearly complete IPA
      removal could be achieved for influent carbon loading between 6 and 88 g/m3 x h.
      The TBAB appears efficient for controlling IPA emission under low-to-high carbon
      loading conditions. Carbon recoveries of 95-99% were achieved demonstrating the
      accuracy of results. Applicable operating conditions of TBAB for controlling IPA
      emission were suggested.

PMID- 12801097
TI  - Microbial consortia that degrade 2,4-DNT by interspecies metabolism: isolation
      and characterisation.
AB  - Two consortia, isolated by selective enrichment from a soil sample of a
      nitroaromatic-contaminated site, degraded 2,4-DNT as their sole nitrogen source
      without accumulating one or more detectable intermediates. Though originating
      from the same sample, the optimised consortia had no common members, indicating
      that selective enrichment resulted in different end points. Consortium 1 and
      consortium 2 contained four and six bacterial species respectively, but both had
      two members that were able to collectively degrade 2,4-DNT. Variovorax paradoxus
      VM685 (consortium 1) and Pseudomonas sp. VM908 (consortium 2) initiate the
      catabolism of 2,4-DNT by an oxidation step, thereby releasing nitrite and forming
      4-methyl-5-nitrocatechol (4M5NC). Both strains contained a gene similar to the
      dntAa gene encoding 2,4-DNT dioxygenase. They subsequently metabolised 4M5NC to 2
      hydroxy-5-methylquinone (2H5MQ) and nitrite, indicative of DntB or 4M5NC
      monooxygenase activity. A second consortium member, Pseudomonas marginalis VM683
      (consortium 1) and P. aeruginosa VM903, Sphingomonas sp. VM904, Stenotrophomonas
      maltophilia VM905 or P. viridiflava VM907 (consortium 2), was found to be
      indispensable for efficient growth of the consortia on 2,4-DNT and for efficient
      metabolisation of the intermediates 4M5NC and 2H5MQ. Knowledge about the
      interactions in this step of the degradation pathway is rather limited. In
      addition, both consortia can use 2,4-DNT as sole nitrogen and carbon source. A
      gene similar to the dntD gene of Burkholderia sp. strain DNT that catalyses ring
      fission was demonstrated by DNA hybridisation in the second member strains. To
      our knowledge, this is the first time that consortia are shown to be necessary
      for 2,4-DNT degradation.

PMID- 12801098
TI  - Improving the biotreatment of hydrocarbons-contaminated soils by addition of
      activated sludge taken from the wastewater treatment facilities of an oil
      refinery.
AB  - Addition of activated sludge taken from the wastewater treatment facilities of an
      oil refinery to a soil contaminated with oily sludge stimulated hydrocarbon
      biodegradation in microcosms, bioreactors and biopile. Microcosms containing 50 g
      of soil to which 0.07% (w/w) of activated sludge was added presented a higher
      degradation of alkanes (80% vs 24%) and polycyclic aromatic hydrocarbons (PAHs)
      (77% vs 49%) as compared to the one receiving only water, after 30 days of
      incubation at room temperature. Addition of ammonium nitrate or sterile sludge
      filtrate instead of activated sludge resulted in a similar removal of PAHs but
      not of alkanes suggesting that the nitrogen contained in the activated sludge
      plays a major role in the degradation of PAHs while microorganisms of the sludge
      are active against alkanes. Addition of sludge also stimulated hydrocarbon
      biodegradation in 10-kg bioreactors operated during 60 days and in a 50-m3
      biopile operated during 126 days. This biopile treatment allowed the use of the
      soil for industrial purpose based on provincial regulation ("C" criteria). In
      contrast, the soil of the control biopile that received only water still exceeded
      C criteria for C10-C50 hydrocarbons, total PAHs, chrysene and benzo[a]anthracene.
      The stimulation effect of sludge was stronger on the 4-rings than on 2-rings
      PAHs. The soil of the biopile that received sludge was 4-5 times less toxic than
      the control. These results suggest that this particular type of activated sludge
      could be used to increase the efficiency of the treatment of hydrocarbon
      contaminated soils in a biopile.

PMID- 12801099
TI  - Evidence of cytochrome P450-catalyzed cleavage of the ether bond of
      phenoxybutyrate herbicides in Rhodococcus erythropolis K2-3.
AB  - Bacterial strain Rhodococcus erythropolis K2-3 can cleave the ether bond of the
      phenoxybutyrate herbicides, i.e., 4-(2,4-dichlorophenoxy)butyrate (2,4-DB) and 4
      (4-chloro-2-methylphenoxy)butyrate (MCPB), by an enzyme system that is
      constitutively expressed. The enzyme(s) involved were investigated in this study.
      The rate of disappearance of 2,4-DB determined in a whole cell assay amounted to
      0.6 mmol/h x g(dry mass). Carbon monoxide difference spectra of dithionite
      reduced whole cells and crude cell extracts suggested that strain K2-3 contains a
      soluble cytochrome P450 (P450), named P450(PB-1). The addition of various
      phenoxybutyrate substrates to crude cell extracts resulted in typical difference
      spectra following the type I pattern of substrate binding with P450. The rate of
      2,4-DB cleavage was reduced by inhibitors of P450: 5 mM metyrapone and carbon
      monoxide at a CO/O2 ratio of 10 reduced the activity by about 20%, and 70%,
      respectively. The ether cleaving activity completely disappeared after disruption
      of the cells and could not be detected in crude extracts. To elucidate the
      enzymatic basis of this reaction, P450 was partially purified. With the resulting
      enzyme preparation, 2,4-DB cleavage activity was re-established, becoming
      measurable after the addition of either phenazine methosulfate or ferredoxin and
      ferredoxin/NADP oxidoreductase from spinach. We detected no activities
      attributable to alpha-ketoglutarate-dependent dioxygenase or NAD(P)H-dependent
      monooxygenase. These results collectively indicate that cleavage of the ether
      bond of phenoxybutyrate herbicides is catalyzed by P450-mediated activity in this
      strain. One of the products derived from this reaction is dichlorophenol, and
      comparative chromatographic analyses suggest that the other product is a C4
      carbonic acid, most likely succinic semialdehyde/succinate.

PMID- 12801100
TI  - Stoichiometry of the aerobic biodegradation of the organic fraction of municipal
      solid waste (MSW).
AB  - An elemental analysis was applied to describe the composition of the organic
      fraction of municipal solid waste (MSW). The initial elemental composition was
      constant at C5H8.5O4N0.2. The changes of the composition during the
      biodegradation process and the final waste composition were strictly dependent on
      the process conditions. The decrease in carbon content due to biodegradation
      increased with temperature at which the experiments were conducted, from 20% at
      20 degrees C to about 40% at 37-42 degrees C after 96 hours. It was correlated
      with the amount of oxygen that was utilised in the investigated processes of
      aerobic biodegradation of the waste suspension. The amount of oxygen required for
      biodegradation of organic fraction of MSW was estimated on the basis of
      stoichiometric equations and increased from 0.92 moles per 1 mole of waste at 20
      degrees C to 1.6 moles at 42 degrees C within 96 hours of the experiments.

PMID- 12801101
TI  - Anaerobic biodegradation of linear alkylbenzene sulfonate (LAS) in upflow
      anaerobic sludge blanket (UASB) reactors.
AB  - The anaerobic biodegradation of Linear Alkylbenzene Sulfonate (LAS) was studied
      in Upflow Anaerobic Sludge Blanket Reactors (UASB). One reactor was fed with
      easily degradable substrates and commercial LAS solution during a period of 3
      months (Reactor 1), meanwhile a second reactor was fed with a commercial LAS
      solution without co-substrate (Reactor 2) during 4 months. Both reactors were
      operated with an organic loading rate of 4-5 mg-LAS/l x day and a hydraulic
      retention time of one day. The LAS biodegradation was determined by full mass
      balance. LAS was analysed by HPLC in the liquid phase (influent and effluent
      streams of the reactors) as well as in the solid phase (granular sludge used as
      biomass). The results indicate a high level of removal (primary biodegradation:
      64-85%). Biodegradation was higher in the absence of external co-substrates than
      in the presence of additional sources of carbon. This indicates that the
      surfactant can be partially used as carbon and energy source by anaerobic
      bacteria. Under the operating conditions used, inhibition of the methanogenic
      activity or any other negative effects on the biomass due to the presence of LAS
      were not observed. The methanogenic activity remained high and stable throughout
      the experiment.

PMID- 12801102
TI  - Growth in weight and length.
AB  - Some of the complex factors that can affect growth in weight but especially in
      height are discussed. It is emphasized that although due attention needs to be
      paid to diet and the regular provision of the extra macro- and micro-nutrients
      needed during catch-up growth, other considerations are just as important.
      CONCLUSION: As well as dealing with the problem of poor sanitation and consequent
      frequent infection in developing countries, social stimulation and the
      restoration of a feeling of well-being and general happiness can be just as
      important.

PMID- 12801103
TI  - Extemporaneous (magistral) preparation of oral medicines for children in European
      hospitals.
AB  - The lack of availability of licensed paediatric medicines forces pharmacists to
      compound drugs into a form that children can tolerate. There is a lack of
      information to support much of this practice and standards tend to vary. Suitable
      licensed alternatives are often available in other countries but importing
      restrictions complicate obtaining them. CONCLUSION: Regulatory action is needed
      to simplify licensing and importation processes to facilitate universal access to
      suitable paediatric medicines.

PMID- 12801104
TI  - Snoring in infancy.
AB  - Obstructive sleep apnoea (OSAS) in infants is a risk factor for sudden infant
      death (SIDS). Snoring in a young child should raise suspicion of OSAS, and
      according to recent AAP guidelines, evaluation and polysomnographic studies are
      recommended in selected cases as the diagnostic test of choice. However, infants
      under 1 y of age are excluded from the guidelines, and interventions to prevent
      SIDS based on respiratory monitoring remains a matter of controversy. As often
      happens, the evidence we need most is usually scarce.

PMID- 12801105
TI  - The Centers for Disease Control and Prevention 2000 growth charts and the growth
      of breastfed infants.
AB  - AIM: To evaluate the performance of the 2000 Centers for Disease Control and
      Prevention (CDC) growth charts in comparison with the National Center for Health
      Statistics/World Health Organization (NCHS/WHO) reference as a tool for assessing
      growth in healthy breastfed infants. METHODS: Weight and length measurements were
      obtained from a pooled longitudinal sample of 226 healthy breastfed infants.
      Weight-for-age (WA), length-for-age (LA) and weight-for-length (WL) z-scores
      based on the CDC and NCHS/WHO references were computed for each child. Age
      specific mean z-scores and proportions below and above specific cut-off points
      were calculated. RESULTS: Breastfed infants grow more rapidly in the first 2 mo
      of life and less rapidly from 3 to 12 mo in relation to the CDC WA curves.
      Similarly, breastfed infants experience greater linear growth than the CDC median
      until age 4 mo. Thereafter, the mean LA z-score declines until month 9. Apart
      from a 1-mo difference in the time when linear growth begins to falter, the
      pattern of growth is remarkably similar when compared with the two references.
      The growth trajectories indicate that infants in the CDC reference are heavier
      and shorter than the NCHS/WHO reference population. Combining the two
      measurements as WL reveals that higher weight overrides lower length in the CDC
      versus the NCHS population, thus the estimated prevalence of wasting is higher by
      the CDC reference. CONCLUSION: As was the case when compared with the NCHS/WHO
      reference, there are notable differences in the growth trajectory of breastfed
      infants examined against the CDC reference. A reference based on healthy
      breastfed infants is required if the growth patterns of infants following
      international feeding recommendations are to be correctly assessed.

PMID- 12801106
TI  - Tracking of serum total cholesterol during childhood: an 8-year follow-up
      population-based family study in eastern Finland.
AB  - AIM: To investigate the tracking of serum total cholesterol (TC) during
      childhood. METHODS: All children born during 1981-1982 in a rural community of
      eastern Finland were followed at 6 mo, 7 y and 15 y of age. The full follow-up
      period was completed by 138 out of 205 children, of whom 82 (33 girls) had TC
      measured at 7 y and 15 y of age (-7 y, -15 y). The main outcome measurement was
      TC (mmol/L). RESULTS: TC-7 y was significantly associated with TC-15 y (r =
      0.655; p-value < 0.001). This correlation did not change significantly after
      accounting for confounders. Children in the highest tertile of TC-7 y had a
      significantly higher risk of being in the highest tertile of TC-15 y compared
      with children in other tertiles of TC-7 y (relative risk = 6.4 (2.9-13.9)). TC-15
      y was predicted positively by TC-7 y (linear regression beta = 0.63; p-value <
      0.001) and parental high TC (TC > or = 5.0 mmol/L in at least one parent) (beta =
      0.58; p-value = 0.030). Birthweight had no significant association with TC during
      childhood. CONCLUSION: The study confirmed the tracking of TC during childhood.
      The identification of children at risk of developing high TC during adolescence
      should take into consideration the child's previous TC values during childhood
      and parental TC status.

PMID- 12801107
TI  - Snoring in the first year of life.
AB  - AIM: To describe the prevalence of snoring in infancy and the factors associated
      with snoring. METHODS: The investigation comprised a cross-sectional study of
      1800 infants. Snoring was ascertained by interviewer-administered questionnaire.
      RESULTS: The prevalence of snoring was 15.8% in the first 4 wk of life and 26.1%
      in the past 2 wk. Snoring in the past 2 wk was associated with increasing age of
      the infant, male gender, maternal smoking, sleep position, number of respiratory
      infections and snoring in the first 4 wk of life after adjustment for potential
      confounders. No associations were found with snoring in the first 4 wk of life.
      CONCLUSION: Snoring is common in infancy. The identified risk factors for snoring
      are probably causally related to snoring. Further studies are needed to establish
      whether snoring in infancy is associated with current or subsequent morbidity.

PMID- 12801108
TI  - Incidence of hyponatraemia and hyponatraemic seizures in severe respiratory
      syncytial virus bronchiolitis.
AB  - AIM: To document the incidence and early evolution of hyponatraemia (serum sodium
      < 136 mmol l(-1)) associated with respiratory syncytial virus (RSV) bronchiolitis
      in infants requiring intensive care. METHODS: In a retrospective review over two
      winter seasons, 130 infants were admitted with confirmed RSV infection, of whom
      39 were excluded because of either pre-existing risk factors for hyponatraemia:
      diuretic therapy (n = 14), cardiac disease (n = 10), renal disease (n = 2) or
      lack of admission sodium data (n = 13). RESULTS: The incidence of admission
      hyponatraemia in the remaining infants (median age 6 wk) was 33% (30/91), with
      11% (10/91) exhibiting a serum sodium less than 130 mmol l(-1) . Hyponatraemic
      and normonatraemic infants were of a similar age (median 6 vs 7 wk, p = 0.82).
      With fluid restriction and diuretic therapy, the incidence of hyponatraemia at 48
      h had decreased to 3.3%, odds ratio 0.07 (95% confidence interval 0.02-0.24, p <
      0.001). Four infants (4%) suffered hyponatraemic seizures at admission (sodium
      114-123 mmol l(-1)); three had received hypotonic intravenous fluids at 100-150
      ml kg(-1) d(-1) before referral to intensive care. All four were managed
      successfully with hypertonic (3%) saline, followed by fluid restriction,
      resulting in immediate termination of seizure activity and normalization of serum
      sodium values over 48 h. CONCLUSION: Hyponatraemia is common among infants with
      RSV bronchiolitis presenting to intensive care. Neurological complications may
      occur and fluid therapy in vulnerable infants should be tailored to reduce this
      risk.

PMID- 12801109
TI  - The importance of follow-up of children with vesicoureteral reflux grade 1.
AB  - AIM: The objectives of this study were, first, to determine the probability of
      detecting vesicoureteral reflux (VUR) into the renal collecting system (VUR grade
      2 or higher) by follow-up cyclic radionuclide cystography (CRC) in children with
      VUR 1 on initial examination, and in children without VUR and with the same
      clinical history; and secondly, to find out whether dividing VUR 1 into three
      subclasses, including possible reflux into the ureter, reflux into the lower
      ureter, and reflux into the whole length of the ureter, enhances detection of
      higher grade reflux in these children. METHODS: 275 children with VUR 1 found on
      initial CRC, and 31 children without reflux and with the same clinical history
      were studied. In total, 414 renal units with VUR 1 of different subclasses and
      198 renal units without reflux were evaluated. RESULTS: Follow-up CRC disclosed
      reflux into the renal collecting system in 20% of children with VUR 1 on initial
      investigation, and in 23% of children with no reflux at the time of initial
      investigation. The probability that follow-up examination would disclose VUR 2 in
      3 in renal units with different subclasses of grade 1 reflux was 8-16%, and did
      not differ significantly from the probability for detecting reflux in kidneys
      with no reflux on initial examination. CONCLUSION: In the absence of recurrent
      urinary tract infection, the management of children with VUR 1 identified by CRC
      can be the same as in children without reflux. Yet, in children with no reflux or
      with VUR 1 detected after urinary tract infection, the probability that reflux
      reaching the pylon was missed should not be underestimated. Dividing VUR 1 into
      subclasses does not seem to be of diagnostic value.

PMID- 12801110
TI  - Late relapse of adrenocortical carcinoma in Beckwith-Wiedemann syndrome.
      Clinical, endocrinological and genetic aspects.
AB  - We report on a girl with an unusual Beckwith-Wiedemann syndrome (BWS) and
      hemihypertrophy, who developed an adrenocortical carcinoma with atypical clinical
      behaviour. At 4 y of age the girls was admitted to hospital with cushingoid
      features, virilization, increased excretion of steroids and low serum ACTH. A
      right-sided adrenocortical carcinoma was removed. At age 12.5 y the cushingoid
      features reappeared together with a tumour in the left thigh. A CT scan of the
      thorax and abdomen revealed pulmonary metastasis only. Corticosteroid excretion
      was increased and serum ACTH level suppressed. The femoral and the pulmonary
      metastases were removed and histology showed adrenocortical carcinoma. Excretion
      of corticosteroids subsequently normalized. Meningeal and pulmonary metastases
      with similar histologies appeared one year later with normal hormone values.
      Twenty-two months after the recurrence the girl died of an intracranial
      metastasis. Southern blot analysis of the LITI transcript in the KvLQT1 gene in
      the BWS region on chromosome 11p15 revealed hypomethylation of the maternal
      allele. CONCLUSION: Adrenocortical carcinoma in childhood may recur years after
      onset and at rare sites and hormonal levels may be an insufficient indicator of
      small metastases.

PMID- 12801111
TI  - Low back pain in Flemish adolescents and the role of perceived social support and
      effect on the perception of back pain.
AB  - AIM: To document the prevalence of low back pain (LBP) in Flemish adolescents and
      to recognize the association between perceived social support and affect and
      medical consultation and reduction of activities. METHODS: The study comprised
      620 adolescents. A questionnaire was used to elicit the characteristics of LBP.
      Perceived social support and affect were investigated using the Personal Resource
      Questionnaire (PRQ) and the Positive Affect Negative Affect Scale (PANAS),
      respectively. Comparisons were made between adolescents with LBP and adolescents
      without LBP. Within the LBP group, answers from adolescents appealing for medical
      advice were compared with those who did not seek advice. Another comparison was
      done between adolescents who reduced their activities and those who did not.
      Descriptive statistics, the median test for two samples, a chi2 test or Fisher's
      exact probability test and logistic regression analysis were used for data
      analysis. RESULTS: Month prevalence of LBP was 24.7%. Thirteen adolescents
      visited a physician or received treatment, pain severity being the sole factor
      associated with the decision. Fifteen adolescents reduced their sports activities
      and 11 reduced or stopped other leisure activities. Pain severity and negative
      affect were the main associated factors. CONCLUSION: The results of the present
      study encourage further research on the role of pain perception and the influence
      of psychosocial factors on back pain in adolescents.

PMID- 12801112
TI  - Treatment of children with Osteogenesis imperfecta in Estonia.
AB  - AIM: To analyse the changes in fracture rate, bone density and histology in
      children with Osteogenesis imperfecta receiving treatment with alendronate (oral
      bisphosphonate) and calcitriol. METHODS: Children treated at Tartu University
      Hospital from 1995 to 2001 were examined for Osteogenesis imperfecta. Radiographs
      and bone density measurements were obtained for all patients at the beginning of
      the study. Four patients also had bone biopsies prior to and one year after
      beginning treatment. The children were then given alendronate in weight-dependent
      dosages and also calcitriol. The number of fractures during the treatment period
      was recorded and follow-up bone density measurements were made. RESULTS: Fifteen
      patients were treated during the 6-y period; mean follow-up approximately 3 y. It
      was found that the number of bone fractures had decreased significantly (p <
      0.0001). Bone density improved in all 15 patients. Histologic studies revealed an
      increased number of osteoblasts and thickness of bone trabeculae as well as a
      more regular bone lamellar structure at the time of the second operation.
      CONCLUSION: The complex treatment of Osteogenesis imperfecta should include
      alendronate and calcitriol to decrease fractures and improve bone mineral
      density.

PMID- 12801113
TI  - A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries
      in a large kindred from Qatar.
AB  - AIM: To describe the clinical spectrum of anomalies of a new type of Ehlers
      Danlos syndrome in 32 patients from a large inter-related extended family in
      Qatar. METHODS: Among the 32 patients (from 22 families), there were 6 affected
      pairs of siblings and 2 families with 3 affected siblings. The male to female
      ratio was 2:1, ages ranging from birth to 18 y (mean 7.4 y). RESULTS: Anomalies
      included a variable degree of skin hyperextensibility, hypermobility of small and
      large joints, and tortuous systemic arteries. Peculiar facial features included
      epicanthic folds, flat saggy cheeks, elongated faces and micrognathia. The
      combination of an elongated aortic arch and tortuous brachiocephalic arteries was
      seen in 30 patients (93.8%), aneurysm of the ascending aorta in 3 patients
      (9.4%), bifid pulmonary artery in 27 patients (84.4%) and multiple severe
      peripheral stenosis of the right and/or left pulmonary artery in 7 patients
      (21.9%). A prominent aortic knuckle was observed on the chest roentgenograms of
      30 patients (93.8%); inguinal hernia in 11 patients (34%), diaphragmatic hernia
      and/or hiatus hernia in 7 patients (21.9%); and laryngo-tracheomalacia in 2
      patients (6.3%). Generalized muscle hypotonia was found in 15 neonates (46.9%).
      Parental consanguinity involved in all the patients was traced to a common
      ancestor from a large Bedouin tribe in Qatar. These patients are at risk for
      potentially catastrophic arterial rupture. Linkage to the major loci involved in
      Ehlers-Danlos syndrome and other connective tissue disorders, such as Cutis Laxa,
      Familial Aneurysm, and Osteogenesis imperfecta, was excluded by using specific
      DNA markers, confirming the uniqueness of this disorder. CONCLUSION: The study
      describes a large cohort of patients from the same closely related family,
      sharing peculiar dysmorphisim and consistent radiological and echocardiographic
      features different from known types of Ehlers-Danlos syndrome. As known loci
      involved in Ehlers-Danlos syndrome and other connective tissue disorders were
      excluded by specific DNA markers, this appears to be a new type of Ehlers-Danlos
      syndrome or even a new syndrome.

PMID- 12801114
TI  - Calprotectin levels in meconium.
AB  - AIM: To evaluate the effect of gender, gestational age, birthweight, mode of
      delivery, 5'-Apgar score and maternal conditions on calprotectin concentrations
      in meconium. METHODS: Calprotectin was measured in 131 neonates, in the first
      passed meconium. RESULTS: Calprotectin levels (mean +/- SD) resulted in 145.2 +/-
      78.5 mg kg(-1) meconium, significantly correlated with birthweight (r = -0.333; p
      < 0.001), gestational age (r = -0.206; p = 0.018) and 5'-Apgar score (r = -0.243,
      p = 0.035). The estimated regression model was: calprotectin levels (mg kg(-1)) =
      269.58-41.54 weight (kg): r = 0.383, p < 0.001. No differences were found in
      relation to gender, mode of delivery and maternal conditions. CONCLUSION:
      Calprotectin is already present in the first passed meconium, with higher levels
      in preterm and low birthweight neonates, as well as in neonates with some degree
      of perinatal asphyxia, as indicated by the negative correlation with 5'-Apgar
      score. These findings are probably secondary to both the immaturity of the
      intestinal mucosa and its hypoxic-ischaemic damage.

PMID- 12801115
TI  - Concentrations of dioxins and other organochlorines (PCBs, DDTs, HCHs) in human
      milk from Seveso, Milan and a Lombardian rural area in Italy: a study performed
      25 years after the heavy dioxin exposure in Seveso.
AB  - AIM: To investigate whether those who were exposed to high levels of the dioxin
      TCDD 25 years ago in Seveso, northern Italy still have higher than the expected
      levels of dioxins in their fat stores, and to investigate the concentrations of
      dioxins in the breast milk of mothers in Seveso and in two other regions in
      Italy. The load of vertically transmitted dioxins to the next generation, if
      being breastfed, was also investigated. METHODS: As there may be a synergistic
      effect of mixtures of organic chlorines, the concentrations of pesticides such as
      DDTs and PCBs have also been studied in the same human milk samples. Breast milk
      from 12 mothers from Seveso, Central Milan and a Lombardian village was collected
      for analysis during the first week and 1 and 3 mo after delivery. Individual
      samples were used for the analysis of pesticides and PCBs, whereas dioxins were
      analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In
      human milk from Seveso, the TCDD concentration in fat calculated on a fresh
      weight basis was more than twice as high as the level in the other two regions,
      whereas the concentrations of investigated other toxins were lower in Seveso
      possible due to induction of the enzyme cytochrome P4501A, which means that the
      total level of dioxins was the same in all three locations. The congener profile,
      measured as mean toxic equivalency (TEQ) values, was the same in the Italian
      samples as previously reported from Stockholm. The calculations are based on the
      most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher
      in the samples from Milan than in the samples from the other two Italian regions,
      which may be due to the fact that, to a greater extent than in the other regions,
      Milanese food is imported from countries where DDT is still used as a pesticide.
      CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from
      mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD
      that are more than twice as high as those in central Milan and a Lombardian
      village. This means that breastfed infants in Seveso still store an appreciable
      amount of TCDD in their body fat. The health consequences of this fact remain to
      be elucidated. The effect of the high load of DDTs in central Milan also has to
      be considered

PMID- 12801116
TI  - Copper in drinking water: not a strong risk factor for diarrhoea among young
      children. A population-based study from Sweden.
AB  - AIM: To assess whether mean daily intake of copper or maximal concentration of
      copper in drinking water is related to the incidence of diarrhoea and vomiting
      among young children. METHODS: Mean daily intake of copper from drinking water
      was estimated prior to episodes of diarrhoea among 430 children aged 9 to 21 mo.
      A total of 4703 samples of tap water were collected in the homes of the children.
      The mean daily intake of copper and the maximal concentration of copper in
      samples of consumed water were used as measures of exposure. The cumulative
      incidence of acute diarrhoea and vomiting was studied during 12 wk of follow-up.
      Cases of diarrhoea caused by viral and bacterial infections were identified.
      RESULTS: The median copper level of the mean value for each child was 0.61 mg/L
      with 10th and 90th percentiles of 0.04 and 1.57 mg/L. Among the 430 children, 43
      had episodes of acute diarrhoea, of which 23 had no identified viral or bacterial
      origin, and vomiting was reported in 95 children. No significant associations
      were found between daily intake of copper or maximal concentration of copper in
      drinking water and the risk of diarrhoea or vomiting. CONCLUSION: There is
      unlikely to be a strong association between daily intake of copper or maximal
      concentration of copper in drinking water and the risk of diarrhoea or vomiting
      within the range of copper intakes/concentrations studied.

PMID- 12801117
TI  - Cost of hospitalization for respiratory syncytial virus chest infection and
      implications for passive immunization strategies in a developing nation.
AB  - Respiratory syncytial virus (RSV) chest infection is a common cause of
      hospitalization in the very young child. The aim of this study was to determine
      the direct cost of resource utilization in the treatment of children hospitalized
      with RSV chest infection and the potential cost-savings with passive immunization
      for high-risk infants. An audit of the hospital resource consumption and its
      costs was performed for 216 children aged < 24 mo admitted with RSV chest
      infection between 1995 and 1997. The cost-saving potential of passive
      immunization using monoclonal RSV antibodies during the RSV season was determined
      by assuming an 0.55 efficacy in hospitalization reduction when administered to
      "high-risk" infants according to the guidelines outlined by the American Academy
      of Pediatrics (AAP). The hospital treatment cost of 1064 bed-days amounted to USD
      64 277.70. Each child occupied a median of 4.0 bed-days at a median cost of USD
      169.99 (IQ1 128.08, IQ3 248.47). Children, who were ex-premature or with an
      underlying illness were more likely to have a longer hospital stay, higher
      treatment costs and need for intensive care. Ten (42%) of 24 ex-premature infants
      fulfilled the recommended criteria for passive immunization. Its use resulted in
      an incremental cost of USD 31.39 to a potential cost saving of USD 0.91 per
      infant for each hospital day saved. CONCLUSION: Ex-prematurity and the presence
      of an underlying illness results in escalation of the direct treatment cost of
      RSV chest infection. Current guidelines for use of passive RSV immunization do
      not appear to be cost-effective if adopted for Malaysian infants.

PMID- 12801118
TI  - Extemporaneous (magistral) preparation of oral medicines for children in European
      hospitals.
AB  - AIM: To evaluate methods of preparation of oral medicines in European children's
      hospitals when drugs prescribed are unlicensed or off-label, and to determine
      whether such extemporaneously prepared medicines are available as suitable,
      authorized products in other countries. METHODS: A questionnaire was distributed
      to 41 hospital pharmacists in 18 European countries, requesting information on
      the most frequent extemporaneously prepared oral liquid, powder and capsule
      medicines, and on their formulation and stability. Information was gathered on
      the availability of suitable authorized forms of these medicines in other
      European countries, the USA and Australia. RESULTS: 21 questionnaires from 16
      countries returned showed that the methods of extemporaneous preparation vary in
      different European countries with, for example, liquid preparations predominating
      in England and Sweden, capsules in France and Spain, and powders in Finland and
      Italy. The top 20 preparations are made in many different strengths and
      formulations. The same drug may be prepared in liquid, capsule or powder form,
      depending on the country. Many of the extemporaneous preparations were available
      as suitable authorized paediatric medicines in other countries. The quality of
      information available on formulation and stability was limited, and there was
      concern about the availability and quality of chemical ingredients. CONCLUSION:
      Preparation of children's oral medicines is subject to much variation in
      hospitals throughout Europe and there is little harmonization of formulations or
      information on stability of products. The European Union could be the focus for
      improving the availability of appropriate authorized medicines for children and
      ensuring that when extemporaneous preparation is necessary it is of a common high
      standard.

PMID- 12801119
TI  - Seasonality of growth and the relationship between weight and height gain in
      children under three years of age in rural Malawi.
AB  - AIM: To describe the seasonal pattern of growth and analyse the relationship
      between weight and height gain in children under 3 y of age. METHODS: A
      population-based cohort of 767 children was prospectively followed from birth
      until 36 mo of age in rural Malawi, southeast Africa. Weight and height
      measurements were collected at monthly intervals until 18 mo of age and quarterly
      thereafter. Gains in weight and height and prevalence of malnutrition in
      different seasons were calculated. The relationship between weight and height
      gain was analysed using a series of correlation analyses. RESULTS: Both weight
      gain and linear growth velocity showed an age-dependent seasonal pattern. After
      infancy, periods of maximal or minimal height increments systematically occurred
      3 mo after those for weight gain. The prevalence of malnutrition also followed a
      seasonal pattern, peaking a few months after periods of reduced growth. Despite
      the overall pattern, weight gain and subsequent linear growth were not correlated
      on an individual level. At any point, however, a child's weight for height was
      directly, albeit weakly, correlated to height gain in the subsequent 3-mo
      interval. CONCLUSION: Growth of children under 3 y of age followed an age
      dependent seasonal pattern. The poor correlation between children's weight and
      height increments suggests that seasonality affected weight gain and linear
      growth through different mechanisms.

PMID- 12801120
TI  - Neonatal ovarian cysts.
AB  - Foetal and neonatal ovarian cysts have previously been considered uncommon. With
      the development of sonography, however, the detection of cysts has increased. As
      ovarian cyst formation in the perinatal period is a self-limiting process,
      treatment options depend on the risk of complications and on the ability to
      differentiate these benign cysts from other pathology. The history of two
      neonates with an ovarian cyst detected antenatally with ultrasound techniques is
      described. CONCLUSION: It is important that paediatricians have knowledge about
      the incidence, treatment and prognosis of foetal neonatal ovarian cysts.

PMID- 12801121
TI  - Carnitine-acylcarnitine translocase deficiency: case report and review of the
      literature.
AB  - AIM: Carnitine-acylcarnitine translocase (CACT) deficiency is an inborn error of
      metabolism involving the mitochondrial beta-oxidation of long-chain fatty acids.
      The aim of this study was to report on a new case (neonatal phenotype) and review
      the literature data on 24 previously reported cases. METHODS: Clinical data of
      the new case are described and compared with the previous reports. RESULTS: The
      patient with a novel mutation had clinical features and biochemical findings
      similar to those of the other reported patients. CONCLUSION: CACT is an entity in
      which clinical encephalopathy, hepatomegaly and arrythmias are common.
      Hyperammonaemia and elevation of creatine kinase seem to be constant findings as
      in other disorders of mitochondrial beta-oxidation of long-chain fatty acids. The
      mortality rate is very high.

PMID- 12801122
TI  - Intravenous immunoglobulin therapy for acute cerebellar ataxia.
AB  - A case of acute cerebellar ataxia without any prodromal illness showed cerebellar
      hypoperfusion on 123I-iodoamphetamine single photon emission computed tomography.
      The symptoms did not resolve spontaneously or with methylprednisolone pulse
      therapy but disappeared rapidly with intravenous immunoglobulin therapy.
      CONCLUSION: Intravenous immunoglobulin therapy is worth considering in acute
      cerebellar ataxia that does not respond to high-dose steroid therapy.

PMID- 12801123
TI  - Paraneoplastic limbic encephalitis masquerading as chronic behavioural
      disturbance in an adolescent girl.
AB  - AIM: To describe an unusual but treatable cause of behavioural disturbance in
      adolescence. METHODS: The case is reported of a 15-y-old girl presenting with
      acute confusion, memory problems and psychotic symptoms following an 18-mo
      history of change in personality, school failure and running away from home. A
      review of the literature is also presented. RESULTS: Microbiology, toxicology,
      computed tomography and magnetic resonance imaging did not show any pathology of
      the central nervous system. Bilateral ovarian immature teratomas were eventually
      diagnosed and removed. The rapid improvement in the patient's mental and
      cognitive functions after corticosteroid treatment and the abnormality shown on
      the single photon emission computed tomography suggested a diagnosis of
      paraneoplastic limbic encephalitis. CONCLUSION: Paediatricians and neurologists
      should be aware of this rare disease entity among the more common conditions of
      behavioural problems and substance abuse in adolescents.

PMID- 12801124
TI  - Splenic abscess caused by group A beta-haemolytic streptococcus.
AB  - A case of a pyoderma complicated with splenic abscess and bacteraemia caused by
      group A streptococcus was treated successfully with antibiotics alone for 4
      weeks. To our knowledge, this is the first reported case of splenic abscess
      associated with group A streptococcal bacteraemia. Advances in antibiotic therapy
      and imaging techniques have improved the management and outcomes of splenic
      abscesses. Clinicians should be aware of the possibility of splenic abscess after
      a pyoderma or a sepsis-like episode. CONCLUSION: Splenic abscesses can be
      diagnosed by serial ultrasound or CT scan examinations and should be treated with
      antibiotics for 4-6 weeks.

PMID- 12801125
TI  - Systemic lupus erythematosus initially presenting as idiopathic juvenile
      arthritis with positive antinuclear antibodies.

PMID- 12801126
TI  - Acute rheumatic fever and Henoch-Schnlein purpura.

PMID- 12801127
TI  - Radiation therapy dose delivery.
AB  - In an investigation by the Swedish Cancer Society, the present status critical
      issues and future aspects and potentials in each of nine major areas of radiation
      therapy research were described by an expert group. The report presented here
      deals with radiation therapy dose delivery. dose distributions, beam shaping and
      intensity modulation.

PMID- 12801128
TI  - Biological response to radiation therapy.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and potentials were described by an expert group for
      each of nine major areas of radiation therapy research. This article deals with
      biological response to radiation. Separate sections deal with molecular responses
      to radiation, the stem cell and clonogenic cell concepts and the importance of
      cell proliferation, cell and tissue responses to doses above and below 1 Gy,
      respectively, the potential role of intercellular signalling pathways, the so
      called bystander effect and radiation biology-based therapy planning and
      treatment optimization.

PMID- 12801129
TI  - The potential of proton and light ion beams in radiotherapy.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and potentials were described by an expert group for
      each of nine major areas of radiation therapy research. The present report deals
      with the potential of proton and light ion beams in radiotherapy.

PMID- 12801130
TI  - Research and development of radiation therapy in clinical routines.
AB  - In an investigation conducted by the Swedish Cancer Society, the present status,
      critical issues and future aspects and potentials were described by an expert
      group for each of nine major areas of radiation therapy research. In this report,
      research and development in radiation therapy clinical routines is described. The
      terms research, development, quality assurance, quality control and clinical
      routines in radiation therapy are also defined.

PMID- 12801131
TI  - Biologically optimized 3-dimensional in vivo predictive assay-based radiation
      therapy using positron emission tomography-computerized tomography imaging.
AB  - PET-CT is probably the ultimate tool for accurate tumor imaging and 3-dimensional
      in vivo predictive assay of radiation sensitivity. By imaging the tumor twice
      during the early course of therapy, it should be possible to quantify both the
      tumor responsiveness to therapy and the rate of loss of functional tumor cells
      using the presently derived equations. This new information is ideal for use
      together with biologically based therapy optimization and makes it possible
      accurately to quantitate the dose-response relation, at least for the bulk of the
      tumor cells. Since the tumor responsiveness is available after about one and a
      half weeks of therapy, the information is also ideal for use with adaptive
      therapy where all forms of deviations from the original treatment plan can be
      accurately corrected for since they generally influence the still functional, but
      mainly doomed tumor cell compartment. Thus, uncertainties such as: 1) the
      geometric misalignment of the therapeutic beam with the tumor, 2) deviations of
      the delivered dose distribution from the planned delivery whether due to 3) an
      erroneous treatment planning algorithm or 4) treatment equipment uncertainties
      and 5) deviations in the anticipated responsiveness of the tumor of the patient
      based on historical response data, can all be taken into account. Fortunately,
      when a larger tumor cell compartment than expected is seen an increased dose
      during the remainder of the treatment should always be delivered independently on
      whichever combination of the above deviations was the true reason. With high
      energy photon and hadron therapy it is even possible to image the integral dose
      delivery in vivo during or after a treatment using PET-CT imaging. The high
      energy photons above about 20 MeV produce positron emitters through photonuclear
      reactions in tissue which are proportional to the photon fluence and thus
      approximately also to the absorbed dose. Light ion beams, the ultimate radiation
      modality with regard to physical and biological selectivity, instead produce PET
      emitters through direct nuclear interactions in tissue, but can also be used as
      radioactive beams consisting of intrinsic PET emitters such as 8B, 11C, 13N and
      15O. These radioactive beams allow more accurate imaging of the Bragg peak
      distribution and thus indirectly the absorbed dose. The most universal feedback
      for adaptive radiation therapy would then be to use the measured image of mean
      dose delivery during the early part of the treatment while revising the treatment
      plan based on the initially planned dose distribution and the radiation
      responsiveness of the tumor as seen after the first week or two of therapy. By
      this so-called BIO-ART approach (Biologically Optimized 3D in vivo predictive
      Assay-based Radiation Therapy) radiation therapy optimization may become an
      almost exact science, where the patient's true individual radiation response,
      considering hypoxia and general radiation resistance as well as possible dose
      delivery and planning errors, is taken into account.

PMID- 12801132
TI  - Disease-related distress in parents of children with cancer at various stages
      after the time of diagnosis.
AB  - This study evaluates and describes disease-related distress in parents, with
      particular focus on the association between the time elapsed since the child's
      cancer diagnosis and a number of indicators of distress. In a cross-sectional
      design, 264 mothers and fathers of children with various malignancies completed a
      multidimensional questionnaire focusing on 11 illness-specific and general
      indicators of distress. Parents were assessed from 4 weeks to 14 years after the
      child's diagnosis, and age of children at onset of illness ranged from newly born
      to 21 years (mean approximately 6 years). The levels of distress related to loss
      of control, self-esteem, anxiety, depression, sleep disturbances, and
      psychological and physical distress were lower among parents for whom a longer
      period of time had elapsed from the time of diagnosis. However, the time elapsed
      could not explain all of the variation in these stress reactions, or any of the
      variation in uncertainty, disease-related fear and loneliness. The child's age at
      diagnosis and treatment situation at assessment were surpassed by time elapsed
      since diagnosis as predictors of variance in parental distress. The pattern
      observed indicates the presence of disease-related distress even years after the
      completion of medical treatment. The findings point to the need for research to
      identify parents at particular risk of suffering long-term harmful consequences
      from the prolonged stress of parenting a child with cancer. The necessity of
      longitudinal studies to evaluate the proportion of acute stress in relation to
      chronic or cumulative parental stress is emphasized.

PMID- 12801133
TI  - Biodistribution and pharmacokinetics of 111In-dTPA-labelled pegylated liposomes
      after intraperitoneal injection.
AB  - The biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated
      liposomes (IDLPL) and unencapsulated 111In-DTPA administered by the
      intraperitoneal (i.p.) and i.v. routes in non-tumour-bearing mice were compared.
      Mice received i.p. or i.v. injections of 0.37 MBq 111In-DTPA either encapsulated
      in liposomes or as an unencapsulated agent. A variety of tissues were dissected
      from 5 min to 192 h to determine the biodistribution and pharmacokinetics.
      Injection of IDLPL via the i.p. route caused a 74-fold increase in the area under
      the concentration (AUC) versus time curve in the peritoneum compared to
      unencapsulated 111In-DTPA. Similarly, the AUC for all the intra-abdominal tissues
      was increased significantly (20-427-fold). When i.p. IDLPLs were compared
      directly with i.v. IDLPLs, more modest changes were seen. There were increases in
      AUC for peritoneum (1.4-fold), ovary (1.3-fold), stomach (2.9-fold), pancreas
      (3.6-fold). small intestine (1.5-fold). colon (1.2-fold), gallbladder (5.1-fold)
      and adrenal gland (2.1-fold). These data support the development of i.p.
      liposomal chemotherapy for the treatment of intraperitoneal malignant disease.

PMID- 12801134
TI  - Evaluation of objective measures of smoking status--a prospective clinical study
      in a group of head and neck cancer patients treated with radiotherapy.
AB  - The present study was undertaken to evaluate objective measures of the smoking
      status of head and neck cancer patients during the course of radiotherapy. This
      was done by conducting a weekly structured interview, and measurement of carbon
      monoxide in expired air and of serum concentration of cotinine, the major
      metabolite of nicotine. These methods were tested prospectively in a series of 20
      patients with head and neck cancer treated with radiotherapy. The results showed
      significant differences in the levels of end-expired carbon monoxide as well as
      serum cotinine among the different self-reported smoking groups. Combining the
      two objective measures and the interview data, the study revealed that up to 50%
      of self-reported non-smokers were in fact smoking actively. Measurement of end
      expired carbon monoxide levels was found to be a precise indicator of smoking in
      the hours preceding measurement. Serum cotinine was a valuable measure of true
      smoking status. Assuming that this assay reflects the true smoking status,
      sensitivity, specificity and positive predictive value of self-reporting in this
      patient population was 79%, 80%, and 92%, respectively. In research aiming to
      investigate possible relations between smoking and radiotherapy, it is
      recommended that patients' smoking status be evaluated objectively as a
      supplement to self-reporting, at least in the head and neck cancer patients.

PMID- 12801135
TI  - Prognostic factors, pattern of recurrence and survival in a Danish bladder cancer
      cohort treated with radical cystectomy.
AB  - A cohort of 248 consecutive patients with bladder cancer undergoing radical
      cystectomy between 1992 and 98 was retrospectively followed from diagnosis until
      death. Prognostic factors, pattern of recurrence and survival were analysed.
      Pathological T and N, angiolymphatic and perineural invasion had an independent
      prognostic influence on survival. Patients without muscle-invasive tumour (Ta,
      T1) had a good prognosis, whereas patients with primarily superficial tumour
      progressing to muscle-invasive tumour had a significantly poorer outcome. Forty
      six percent of these patients developed recurrences in the follow-up period, with
      a median time from recurrence to death of 5 months. The 5-year disease-specific
      survival for all 248 patients was 57%. Patients with pT4b or N + all died within
      3 years. Patients with positive lymph nodes or T4b were not curable with
      cystectomy alone. Patients with advanced T or with perineural/vessel invasion are
      in need of improved treatment options. Patients with superficial tumours at high
      risk of progression should be offered early cystectomy.

PMID- 12801136
TI  - Chromosome instability and progression in urothelial cell carcinoma of the
      bladder.
AB  - Superficial urothelial cell carcinoma (UCC) is a heterogeneous group of neoplasia
      with an unpredictable clinical course. Numerical alterations of chromosomes 7, 9
      and 17 in superficial and invasive UCCs were analysed to evaluate the importance
      of chromosome instability in the progression of these tumours. Our sample
      consisted of 75 patients (47 with superficial and 28 with invasive bladder
      tumours). In situ hybridization using centromeric probes for chromosomes 7, 9 and
      17 was done for the chromosome analysis in paraffin-embedded tissues. From the
      results obtained it can be concluded that losses of genetic material seem to be
      important early events in the carcinogenesis of the urothelium, but during
      progression of UCCs there seems to be a selection of those cells with gains of
      genetic material. This chromosome instability may be due to the acquisition of
      mechanisms involved in aneuploidization, namely p53 function disorders.

PMID- 12801137
TI  - The diagnosis of lung cancer using 1064-nm excited near-infrared multichannel
      Raman spectroscopy.
AB  - PURPOSE: Raman spectroscopy is based on Raman scattering of light from molecules.
      Because the wavelength of Raman scattered light depends on molecular composition,
      Raman spectra provide highly useful information about molecular composition. It
      has already been shown that Raman spectroscopy is potentially useful for the
      clinical diagnosis of malignant tumors. However, this technique had never been
      applied to the diagnosis of lung cancers, primarily because of interference from
      the strong fluorescence emitted from lung tissues. Our purpose was to examine the
      effectiveness of near-infrared Raman spectroscopy for the diagnosis of lung
      cancers. METHODS: We constructed a new near-infrared multichannel Raman system
      that is capable of measuring high signal-to-noise ratio, fluorescence-free Raman
      spectra of lung tissues within a measurement time of 1 second. Using this system,
      we collected a total of 210 Raman spectra from cancerous and non-cancerous lung
      tissues and analyzed these spectra by a least-squares fitting procedure for
      cancer diagnosis. RESULTS: The resultant sensitivity of cancer prediction was as
      high as 91%, with 97% specificity and an error margin of p<0.0001 according to
      Fisher's exact test. CONCLUSIONS: A method of diagnosing lung cancer efficiently
      and objectively using Raman spectroscopy has thus been established.

PMID- 12801138
TI  - HRCT findings of pulmonary complications in non-AIDS immunocompromised patients:
      are they useful in differential diagnosis?
AB  - PURPOSE: This study was designed to evaluate the diagnostic value of
      characteristic HRCT findings in the differential diagnosis of acute pulmonary
      complications (APCs) in immunocompromised patients and to investigate how to
      improve diagnostic accuracy. MATERIALS AND METHODS: We reviewed the chest CT
      images of 103 consecutive immunocompromised non-AIDS patients with APCs. The
      presence, extent, and anatomical distribution of the CT findings were assessed by
      two radiologists. The sensitivity and positive predictive value (PPV) of each
      criterion determined by the combination of CT findings that were characteristic
      in previous studies were calculated. RESULTS: The average sensitivity of each
      criterion was 0.50 in the total cases. There were many false positives, and the
      PPVs of some criteria were low. Among the significantly less frequent CT
      findings, the frequency of bronchovascular bundle thickening was 0% in
      cytomegaloviral pneumonia (CMV P). The absence of this finding improved the
      diagnostic accuracy of CMV P. CONCLUSION: Because the combination of only
      characteristic HRCT findings in each disease was of relatively limited value in
      making a diagnosis, infrequent findings should be also added to the CT criteria
      to improve accuracy.

PMID- 12801139
TI  - Four-dimensional computed tomography (4D CT)--concepts and preliminary
      development.
AB  - Four-dimensional computed tomography (4D CT) is a dynamic volume imaging system
      of moving organs with an image quality comparable to that of conventional CT. 4D
      CT will be realized by several technical breakthroughs for dynamic cone-beam CT:
      (1) a large-area two-dimensional (2D) detector; (2) high-speed data transfer
      system; (3) reconstruction algorithms; (4) ultra-high-speed reconstruction
      computer; and (5) high-speed, continuously rotating gantry. Among these,
      development of the 2D detector is one of the main tasks because it should have as
      wide a dynamic range and as high a data acquisition speed (view rate) as present
      CT detectors. We are now developing a 4D CT scanner together with the key
      components. It will take one volume image in 0.5 sec with a 3D matrix of 512 x
      512 x 512. This paper describes the concepts and designs of the 4D CT system, as
      well as preliminary development of the 2D detector.

PMID- 12801140
TI  - Coronal multiplanar reconstruction view from isotropic voxel data sets obtained
      with multidetector-row CT: assessment of detection and size of mediastinal and
      hilar lymph nodes.
AB  - OBJECTIVE: To assess the detection and size of mediastinal and hilar lymph nodes
      by multiplanar reconstruction (MPR) view from isotropic voxel data sets obtained
      with multidetector-row computed tomography (MDCT). MATERIALS AND METHODS: Thin
      section CT of 27 patients with mediastinal or hilar lymph node swelling was
      obtained with a 25.6-cm FOV, 512 x 512 matrix, and two protocols: A) 0.5-mm
      collimation, 0.3-mm interval, and B) 2-mm collimation, 1-mm interval. MPR views
      with a 0.5-mm slice thickness were obtained from these two data sets.
      Postcontrast axial CT used 5-mm collimation (set C). Two observers evaluated the
      presence and cranio-caudal length of swollen lymph nodes. Two other board
      certified chest radiologists evaluated all three sets and established a gold
      standard by consensus. RESULTS: The accuracy of detection was 76%, 73%, and 68%
      for sets A, B, and C, respectively. There was a significant difference between
      sets A and C (McNemar's test: p<0.05) but not between sets A and B or B and C
      (p>0.05). The cranio-caudal length of lymph nodes was significantly correlated
      with the gold standard only in set A (Pearson's correlation coefficient: r=0.53,
      p<0.05). CONCLUSION: Non-contrast enhanced coronal MPR views constructed from
      isotropic voxel data sets may be substituted for axial enhanced CT for the
      evaluation of mediastinal and hilar lymph nodes.

PMID- 12801141
TI  - Dilatation of the heart on postmortem computed tomography (PMCT): comparison with
      live CT.
AB  - PURPOSE: To delineate cardiac structures on postmortem computed tomography (PMCT)
      and quantitatively to prove dilatation of the heart after death. MATERIALS AND
      METHODS: Our subjects were 50 PMCT of non-traumatic deaths and 50 CT of living
      persons (live CT). We measured maximal and minimal diameters of the superior vena
      cava (SVC) at three levels (upper, middle, and lower), the inferior vena cava
      (IVC), pulmonary artery (PA), pulmonary vein (PV), right atrium (RA), and left
      atrium (LA). Then the product of maximal by minimal diameter and the eccentricity
      were calculated. RESULTS: The maximal and minimal diameters of the heart were
      significantly longer than those on live CT except for 1) the maximal diameter of
      the SVC at the upper level and 2) the maximal diameter of the PA. All of the
      products of maximal by minimal diameter on PMCT were significantly larger than
      those on live CT. All of the eccentricities decreased significantly after death
      except LA. CONCLUSION: The heart is dilated on PMCT, and the right side of it
      dilates toward a round shape.

PMID- 12801143
TI  - New insight into the analysis of 6-[18F]fluoro-L-DOPA PET dynamic data in brain
      tissue without an irreversible compartment: comparative study of the Patlak and
      Logan analyses.
AB  - The objective of this study was to show that the Logan analysis is theoretically
      more appropriate than the Patlak analysis for the assessment of 6-[18F] fluoro-L
      DOPA (FDOPA) positron emission tomography (PET) dynamic data in brain tissue
      without an irreversible compartment, e.g., occipital cortex. Another purpose was
      to provide the first application of this analysis to real data. Ten normal
      controls (NC), 10 Parkinson's disease (PD) patients, and 10 Parkinson's disease
      with dementia (PDD) patients underwent FDOPA PET. The Logan analysis and the
      Patlak analysis were applied to the occipital cortex with the cerebellum as a
      reference tissue. In the occipital cortex, the Logan analysis showed a
      significant difference (p=0.018) between NC and PDD patients. However, the Patlak
      analysis showed no significant differences, but larger variances. The Logan
      analysis of FDOPA PET dynamic data in the occipital cortex was considered to be
      theoretically appropriate and to provide new insight into the analysis of that
      region.

PMID- 12801142
TI  - Multivariate analysis of dissemination relapse of medulloblastoma and estimation
      of its time parameter for craniospinal irradiation.
AB  - PURPOSE: To examine in retrospect prognostic factors influencing meningeal
      dissemination relapse of medulloblastoma (MB) and to estimate time parameter
      gamma/alpha of the biologically effective dose for fractionated craniospinal
      irradiation (CSI). MATERIALS AND METHODS: Fifty-eight patients with MB who had
      been treated at our six hospitals from 1980 to 1990, were analyzed by the
      proportional hazards model consisting of radiation factors of both CSI and local
      irradiation (LI), sequential CSI time-lag, and eight non-radiation factors
      (gender, age, performance status, T-stage, dissemination score, extent of
      resection, and use of chemotherapy and immunotherapy). The gamma/alpha for CSI
      was estimated by the profile likelihood method using the maximum value of
      conditionally calculated time-incorporated biologically effective dose, tBEDmax,
      of the field treated with the least dose. RESULTS: Dissemination relapse was seen
      in 23 (40%) patients. Nineteen disseminations occurred within four years, and the
      cumulative dissemination-free rate was 64% at five years. The site of initial
      dissemination relapse was both cranial and spinal in 13 patients (57%).
      Dissemination relapse was accompanied with local failure in 43% (10/23) of
      patients, and four of them were seen later than four years. In the multivariate
      analysis, significant prognostic factors were dissemination score (p=0.0008) and
      total dose of CSI (p=0.018). The estimate of gamma/alpha for CSI was about 0.2
      Gy/day in BED units. In another multivariate analysis including the best-fitted
      tBEDmax, significant prognostic factors were dissemination score and the tBEDmax
      of both CSI (p=0.021) and LI (p=0.024). CONCLUSION: This analysis indicated that
      the dissemination score, total dose of CSI, and tBEDmax of both CSI and LI were
      significantly prognostic for dissemination relapse of MB. The estimate of
      gamma/alpha for CSI was smaller than that derived from our previous analysis for
      LI. However, in order to estimate the time factor for CSI more precisely, a
      larger group of patients treated with concurrent CSI is needed.

PMID- 12801144
TI  - Prevalence of alcohol and drug use in an adolescent training facility.
AB  - This study investigates substance use and crimes among incarcerated adolescents.
      Chart reviews were conducted between 1997-2000 with 186 adolescent, male
      offenders, including information on demographics, substance use, and crimes.
      Results indicate that use of alcohol (88.7%) and marijuana (95.7%) was highly
      prevalent. The most widely committed crimes included possession of a controlled
      substance (31.8%), receiving stolen goods (17.8%), and violation of probation
      (17.2%). Significant differences were observed across racial/ethnic groups; White
      nonHispanic adolescents were more likely to use cocaine, hallucinogens, and
      heroin than adolescents of other races. Future research examining relationships
      between criminal behavior, substance use, and cultural variations in use patterns
      and delinquency will allow more relevant intervention and prevention strategies
      in this population.

PMID- 12801145
TI  - Why do they do it? A qualitative study of adolescent drinking and driving.
AB  - Despite a decline in the prevalence of fatal traffic crashes involving adolescent
      drinking drivers in recent years, underage drinking and driving (DD) and riding
      with drinking drivers (RWDD) remain serious problems. This article reports the
      findings of a qualitative study investigating the influence of beliefs and
      expectancies on adolescents' decisions to participate in DD or RWDD. Forty-four
      adolescents, who in a previous survey admitted to having been involved in either
      DD or RWDD, were interviewed in 2000 about their experiences concerning either
      driving after drinking or getting into a car with a driver who had been drinking.
      Findings indicate that adolescent DD and RWDD are complex behaviors. Expectancies
      and control beliefs do not seem to influence the decision, whereas normative
      beliefs to some extent do. However, findings also indicate that increased
      enforcement of the laws may be helpful in preventing young people from getting
      involved in drinking and driving.

PMID- 12801146
TI  - Sensation-seeking as a moderator of the effects of peer influences, consistency
      with personal aspirations, and perceived harm on marijuana and cigarette use
      among younger adolescents.
AB  - Concurrent effects of peer influence and protective cognitive variables on
      marijuana and cigarette use are hypothesized to be contingent on adolescent
      sensation-seeking. The hypothesis was tested in 1999-2000 using a survey given to
      eighth graders (N=3127) in 20 U.S. middle schools. Results largely supported the
      hypothesis that peer pressure and perceived peer marijuana use had only a
      relatively trivial effect on low sensation-seekers and a much greater effect on
      high sensation-seekers. In addition, aspirations inconsistent with marijuana use
      appeared protective for high sensation-seekers.

PMID- 12801147
TI  - Alcohol and domestic violence in a sample of incidents reported to the police of
      Zurich City.
AB  - The purpose of the study is to examine episodes of domestic violence reported to
      the police, focusing on the drinking behavior of the individuals involved. Over a
      period of 110 days, (November 1999-February 2000) a total of 53 calls to the
      emergency line of the police of the city of Zurich (Switzerland), related to
      domestic violence, were registered. Detailed data concerning the forms of
      violence, the persons involved, their alcohol intake, and the context of the
      incidents were collected in 42 cases by means of structured interviews of the
      officers who achieved the interventions and inquiries. Moreover, interviews by
      agreement of victims were performed in 12 cases, providing complementary data.
      Evidence of alcohol involvement was found in 40% of the investigated situations.
      Police officers thus believed there was a clear link between alcohol and violence
      in at least 26% of the 42 cases. The interviews of the victims suggest a wide
      range of attributions made to the role of alcohol in situations of domestic
      violence.

PMID- 12801148
TI  - The effect of coping skills training on alcohol consumption in heavy social
      drinking.
AB  - This study, designed to evaluate a relapse prevention technique, is based on
      Swedish "heavy" social drinkers who wanted to drink less or quit completely. They
      were recruited by advertisement in national Swedish newspapers and were randomly
      assigned into a control group and a coping skill training group (treatment
      group). Data were collected during the period 1989-1991. Subjects in the coping
      skills training group were taught methods to cope with the craving for alcohol,
      and subjects in the control group had a conventional discussion about their
      problems and the future. All participants also had to set a goal to be reached
      after the treatment. Subjects were asked about their alcohol consumption and
      dependence of alcohol and other alcohol-related behaviors, before, six months,
      and 18 months after treatment. The coping skills training did not prove more
      efficient than nonspecific treatment received in the control group. Instead
      alcohol consumption decreased as a function of the subjects' initial goals,
      independent of treatment and a wish to control drinking seemed more efficient
      than to try to quit drinking completely.

PMID- 12801149
TI  - Drinking practices and other health-related behaviors among adolescents of Sao
      Paulo City, Brazil.
AB  - PURPOSE: (a) detect possible demographic and behavioral differences among young
      episodic heavy drinkers and other young drinkers; (b) investigate the association
      of youth drinking patterns with other health-compromising behaviors. METHODS: The
      data presented are part of a health behavior survey, which used a modified
      version of the Youth Health Risk Behavior Survey (YHRBS) questionnaire. Students
      from public (n = 993) and private schools (n = 815), from 7th to 11th grades were
      investigated in Sao Paulo city. Multivariate logistic regression analyses were
      employed to investigate the association among different drinking practices and
      the various health-compromising behaviors, controlling for age group, gender, and
      school system. Odds Ratios (OR) and their 95% Confidence Intervals (CI) were
      calculated. Episodic Heavy Drinking was defined as having five or more drinks in
      a 2-hour interval, at least once in the last 30 days. RESULTS: Episodic Heavy
      Drinkers (EHDs) tend to be older and males and prefer to drink with friends at
      commercial facilities instead of drinking with their relatives at home. EHDs also
      reported higher percentages of adverse consequences, such as physical fights,
      accidents, and school absenteism after drinking. EHDs are more likely to engage
      in other high-risk behaviors. In the public schools, they were more likely to
      carry guns (OR = 17.0; CI = 3.9-74.8), get involved in physical fights (OR = 8.9;
      CI = 4.4-18.0), attempt suicide (OR = 4.2; CI = 2.0-8.7), and use inhalants (OR =
      2.7; CI = 1.3-5.7) than abstainers. They are also more likely to use marijuana
      (OR = 4.7; CI = 2.2-9.9) and smoke cigarettes (OR = 5.3; CI = 2.7-10.4) than
      moderate drinkers. The results were similar for private schools, with even higher
      ratios of inhalant use (OR = 15.2; CI = 6.2-37.1), when EHDs were compared with
      abstainers and cigarette (OR = 64.5; CI = 8.6-481.0) and marijuana use (OR = 6.5;
      CI = 4.3-9.7), when EHDs were compared with moderate drinkers. CONCLUSIONS: EHDs
      display different drinking habits than other adolescents who drink. Also, they
      are at increased risk for a range of health-compromising behaviors, when compared
      with both abstainers and moderate drinkers.

PMID- 12801150
TI  - Imprisoned drug offenders in Taiwan: a gender-based analysis.
AB  - Using data collected from a 1999 nationwide survey of 700 incarcerated drug users
      in Taiwan, this article compares gender differences with respect to childhood
      experiences, family characteristics, drug use patterns, and criminal histories.
      The results from both bivariate and logistic regression analyses document some
      gender differences and offer tentative support for feminist views. Overall,
      female drug offenders in Taiwan were more likely to have spouses with alcohol or
      drug use-associated problems, experience physical or sexual abuse, grow up in non
      two-parent households, and hold temporary and stereotypical female jobs,
      including prostitution. Compared to men, although female drug offenders reported
      earlier involvement in criminal activities, they were less violent and had fewer
      prior arrests. As for sources, women relied on friends or acquaintances to
      procure their drugs. No gender differences were identified with respect to
      illicit drug type or duration and frequency of use.

PMID- 12801151
TI  - Towards more effective public health programming for injection drug users:
      development and evaluation of the injection drug user quality of life scale.
AB  - The psychometric properties of the Injection Drug User Quality of Life Scale
      (IDUQOL) were assessed in 61 Montreal IDUs in 2001, 85% of whom were
      reinterviewed within four weeks. The reliability of the IDUQOL was acceptable
      (ICC = 0.71) and concordance between the IDUQOL and the Flanagan Quality of Life
      Scale was moderate (Pearson coefficient = 0.57). Quality of life was negatively
      associated with injection cocaine and emergency department use with both
      instruments; these results were more striking for the IDUQOL. The IDUQOL is a
      culturally relevant quality of life instrument with good psychometric properties.
      The IDUQOL may be useful in the development and evaluation of interventions for
      IDUs.

PMID- 12801152
TI  - Gender of physicians with substance use disorders: clinical characteristics,
      treatment utilization, and post-treatment functioning.
AB  - Gender has emerged as an important variable in both the course and treatment of
      substance-use disorders. This study examines the role of gender in a sample of
      physicians (n = 73) treated for substance-use disorders. Pilot data gathered on
      physicians treated during 1995 to 1997, included initial pretreatment
      characteristics, service utilization, and posttreatment functioning. Although
      there were many similarities, important differences emerged among the groups.
      These differences have implications for physician education and training and
      warrant more systematic clinical research.

PMID- 12801153
TI  - Smokeless tobacco and cigarette use among black secondary school students in
      South Africa.
AB  - This study was conducted in 2001 with the aim of providing data on black South
      African secondary school students' tobacco use status, knowledge, and attitudes.
      The sample included 330 Grade 10 and 382 Grade 12 secondary school pupils chosen
      at random from six rural secondary schools in one of the regions in the Northern
      Province of South Africa. Results show a prevalence of 9.1% current smokers among
      boys and 5% among girls, and 8.4% current snuff users among girls and 3.9% among
      boys. The mean age of onset to take snuff was 12.5 years and that for smoking
      cigarettes 14.8 years. Adolescents who reported that some family member or their
      peers used tobacco were more likely to be users of tobacco. Two-thirds of the
      current snuff users believed that using snuff was safer than smoking cigarettes.
      Knowledge was found to be related to attitude but not with tobacco use behavior.
      Awareness of the adverse effects of such tobacco habits was poor and intervention
      programs to curb tobacco use is required.

PMID- 12801154
TI  - MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's
      disease.
AB  - Performance on individual Mini-Mental State Examination (MMSE) items can predict
      incident Alzheimer's disease (AD). The purpose of the current study is to
      determine whether, in nondemented persons with and without the apolipoprotein E-4
      (APOE-4) genetic risk for AD, a subset of MMSE items predict cognitive decline.
      Fifty-four nondemented subjects, 23 with at least one copy of the APOE-4 allele
      and 31 without APOE-4, were given the MMSE and cognitive tests at baseline and 2
      year follow-up. MMSE total score and a subset of MMSE items including delayed
      recall, serial 7s, pentagon, and orientation to time and place were used to
      predict change on cognitive tests. The subset of MMSE items significantly
      predicted decline in visuo-spatial construction and naming in APOE-4 carriers but
      not in noncarriers. Performance on a subset of MMSE items, combined with APOE-4
      genotype, may aid in identifying high-risk persons for research or follow-up.

PMID- 12801155
TI  - Are the clock-drawing test and the MMSE combined interchangeable with CAMCOG as a
      dementia evaluation instrument in a specialized outpatient setting?
AB  - This study examines whether the Clock-Drawing Test (CDT) combined with the Mini
      Mental State Examination (MMSE) is interchangeable with the more detailed and
      lengthy Cambridge Cognitive Examination (CAMCOG) as a dementia evaluation
      instrument in a specialized psychogeriatric outpatient setting: 114 outpatients
      (88 with dementia, 26 with depressive and anxiety disorders) were included. Each
      subject underwent a comprehensive evaluation in which the CAMCOG (MMSE included)
      was administered. DSM-IV diagnoses were independently established. CAMCOG-derived
      clock drawings were blindly scored according to Freedman's method. The authors
      found that a combination of CDT and MMSE enhanced the psychometric properties of
      the above scales approximating them to CAMCOG's. They conclude that CDT in
      combination with the MMSE is valid for differentiation of dementia sufferers from
      nondemented psychiatric controls in a specialistic setting and might replace
      CAMCOG. However, the generalizability of these findings (a wider range of
      diagnoses, primary care settings) still needs to be verified.

PMID- 12801156
TI  - Is subjective memory loss correlated with MMSE scores or dementia?
AB  - OBJECTIVES: (1) To determine if subjective memory loss (SML) is associated with
      Mini-Mental State Examination (MMSE) scores, (2) to determine if this association
      persists after adjustment for other factors, and (3) to determine the sensitivity
      and specificity of SML for dementia. POPULATION: 1751 seniors sampled from a
      population registry. MEASURES: Age, sex, education, SML, the MMSE, and the Center
      for Epidemiologic Studies-Depression (CES-D) scale. Dementia was diagnosed by
      clinical examination. ANALYSIS: Linear regression models were constructed. The
      sensitivity and specificity of SML were determined with a diagnosis of dementia
      being the gold standard. RESULTS: SML was correlated with MMSE scores, even after
      adjusting for age, sex, education, and depressive symptoms. The sensitivity of
      SML was 0.58 (95% confidence interval [CI]: 0.45, 0.71), and the specificity was
      0.76 (95% CI: 0.74, 0.78) for dementia. CONCLUSIONS: SML is correlated with MMSE
      score. However, SML is neither sensitive nor specific for dementia.

PMID- 12801157
TI  - Neuropsychological predictors of everyday memory and everyday functioning in
      patients with mild Alzheimer's disease.
AB  - The contributions of executive function, naming, visuoperception, and delayed
      recall to everyday memory abilities and everyday living activities were examined
      in a sample (n = 24) of mildly impaired Alzheimer's disease (AD) patients.
      Everyday memory was rated independently by the patient and by a caregiver, and
      everyday functioning was rated by a caregiver. For patient-rated everyday memory,
      verbal recall accounted for 23% of the variance, while naming performance alone
      accounted for 56% of the variance in caregiver-rated everyday memory. Executive
      function was a unique and significant predictor of caregiver-rated functional
      daily living skills, accounting for 40% of the variance. Clinician's ratings of
      patient unawareness of deficit correlated with the discrepancy between caregiver
      and patient rating of memory. Caregiver reports of memory impairment appear to be
      influenced by naming abilities, indicating that language dysfunction may be
      misinterpreted as reflecting memory impairment. Helping caregivers distinguish
      between these two abilities may result in more accurate reporting of patients'
      impairments.

PMID- 12801158
TI  - Attitudes of elderly subjects toward "truth telling" for the diagnosis of
      Alzheimer's disease.
AB  - This study expands on previous research regarding attitudes of older adults
      toward disclosure of the diagnosis of Alzheimer's disease (AD). Two hundred
      patients 65 years or older completed a questionnaire assessing opinions about
      being told the diagnosis of AD versus cancer. Most responded they wanted to be
      told if they had AD or terminal cancer (92% for AD, 86.5% for cancer, P = .06).
      Those with personal experience with AD were significantly less likely to want to
      know themselves if they had AD than were those without personal experience (P <
      .0001). A variety of reasons were given for wanting to be told the diagnosis of
      AD, including a small minority (1.7%) who would consider suicide. Although these
      results appear to support recent American Medical Association guidelines favoring
      disclosure of a dementia diagnosis, complex issues remain. Further research is
      needed to develop guidelines for physicians in disclosing dementia diagnoses that
      includes outcome studies of disclosure to patients.

PMID- 12801159
TI  - Comorbidity of psychopathological domains in community-dwelling persons with
      Alzheimer's disease.
AB  - In this post hoc analysis of baseline responses to the CERAD Behavior Rating
      Scale for Dementia in a clinical trial of interventions for agitation in
      Alzheimer's disease (AD), the authors investigated the distribution of, and
      relationships between, agitation, depression, and psychosis in 148 individuals
      with AD. Prevalence of depressive symptoms was highest (78.4%), followed by
      agitation (77.6%) and psychotic symptoms (69.3%); 51.1% of the sample had
      symptoms in all 3 domains. Cross-sectionally, psychotic symptoms were most
      closely associated with Mini-Mental State Examination (MMSE) scores, while
      agitation was less so. Depressive symptoms were relatively consistently prevalent
      across MMSE levels. After controlling for the presence of agitated symptoms,
      psychosis and depression were significantly associated, but neither symptoms of
      psychosis nor of depression were associated with agitation when depression or
      psychosis, respectively, was controlled for. Significant psychopathological
      comorbidity should be considered in the design of clinical trials targeting
      particular psychopathology in this disease population.

PMID- 12801160
TI  - Six-month cognitive improvement in nursing home residents with severe cognitive
      impairment.
AB  - The number of patients in nursing homes with severe cognitive impairment (SCI) is
      growing. The authors compared the characteristics and 6-month outcomes of a
      sample of nursing home residents with SCI to those of other residents. This cross
      sectional and 6-month follow-up study used data from pooled 1990 and 1993 cohorts
      in the Resident Assessment Instrument Evaluation Study. The authors compared
      baseline characteristics of residents with SCI (n = 1304) with all others and
      evaluated 6-month improvement and associated factors in the SCI group. SCI
      residents had poorer nutrition and lower frequencies of most symptoms and chronic
      diseases. Fourteen percent showed 6-month cognitive improvement, associated with
      higher baseline function, antidepressant medication, and recent falls. Nursing
      home residents with SCI had possible underrecognition of medical problems and
      poor nutritional status. Measured improvement may indicate possible
      misclassification for some residents and potential for improvement for others.

PMID- 12801161
TI  - Effect of increasing the dose and duration of sertraline trial in the treatment
      of depressed nursing home residents.
AB  - There has been limited research into defining what constitutes an adequate first
      line antidepressant trial in elderly patients. The authors report the outcome of
      extended, high-dosage sertraline treatment in a sample of nursing home residents
      experiencing residual significant depressive symptoms after 10 weeks of treatment
      with sertraline at a final dosage of 100 mg/day. Subjects who had a Hamilton
      Depression Rating Scale score > or = 12 after 10 weeks of treatment with
      sertraline were eligible for the 8-week open-label extension phase, which
      involved titrating the sertraline dosage to 200 mg/day. The cumulative response
      rate was 52% for the extension phase, compared with 37% for the acute phase.
      Examining acute phase nonresponders, 39% responded during the extension phase.
      Rates of discontinuation due to adverse events were comparable in the 2 phases.
      Our findings suggest that an extended trial or high dosages of sertraline may
      benefit some depressed elderly patients with persistent depression after acute
      treatment.

PMID- 12801162
TI  - Apathy and executive function in depressed elderly.
AB  - Apathy and executive cognitive dysfunction (ECD) are important though
      conceptually different aspects of late-life depression. The primary objective of
      this study was to evaluate the relationship of apathy to ECD. The authors also
      evaluated the relationship of apathy and ECD to global cognitive impairment and
      word generation. Fifty-two elderly subjects with major depression and MMSE scores
      of 15 or greater were evaluated with apathy-related items from the Hamilton
      rating scale for depression (ApHRSD), the Executive Interview (EXIT), the
      Dementia Rating Scale (DRS), and the Controlled Oral Word Association test
      (COWA). ApHRSD scores were not significantly correlated with any of these
      variables. EXIT scores were correlated significantly with DRS and COWA. The
      results suggest that apathy and ECD may be independent of each other in some
      samples of elderly with late-life depression. Correlations may have been reduced
      by low variance for the variables of interest and by psychometric limitations of
      the ApHRSD.

PMID- 12801163
TI  - Unrecognized medical disorders in older psychiatric inpatients in a senior
      behavioral health unit in a university hospital.
AB  - Medical disorders may cause psychiatric symptoms. This study investigated the
      frequency and nature of previously unrecognized medical disorders associated with
      behavioral disturbances in acute geriatric psychiatry inpatients. Data came from
      a chart review of 79 consecutive admissions to the University of California, San
      Diego, Senior Behavioral Health Unit from May 1999 to October 1999. The most
      common Axis I admission diagnoses were depression and psychosis. At admission, 27
      of 79 cases (34%) had unrecognized medical disorders. Comparison of these cases
      with the cases that did not have unrecognized medical disorders found no
      differences in age, education, gender, or cognitive abilities. The group with
      unrecognized medical disorders had more medical disorders (mean 5.0 vs 3.6; P =
      .002). Unrecognized conditions (n) included constipation (7), urinary infection
      (7), and hypothyroidism (5). Elderly psychiatric patients are more likely to have
      physical comorbidity. A large number of medical disorders should alert clinicians
      to look carefully for unrecognized medical disorders.

PMID- 12801164
TI  - Hartmann-Shack technique and refraction across the horizontal visual field.
AB  - We compared refractions across the horizontal visual field, based on different
      analyses of wave aberration obtained with a Hartmann-Shack instrument. The wave
      aberrations had been determined for 6-mm-diameter pupils up to at least the sixth
      Zernike order in five normal subjects [J. Opt. Soc. Am. A 19, 2180 (2002)]. The
      polynomials were converted into refractions based on 6-mm pupils and second-order
      Zernike aberrations (6 mm/2nd order), 3-mm pupils and second-order aberrations (3
      mm/2nd order), 1-mm pupils and second-order aberrations (1 mm/2nd order), and 6
      mm pupils with both second- and fourth-order aberrations (6 mm/4th order). The 3
      mm/2nd-order and 6-mm/2nd-order refractions differed by as much as 0.9 D in mean
      sphere on axis, but the differences reduced markedly toward the edges of the
      visual field. The cylindrical differences between these two analyses were small
      at the center of the visual field (<0.3 D) but increased into the periphery to be
      greater than 1.0 D for some subjects. Much smaller differences in mean sphere and
      cylinder were found when 3-mm/2nd-order refractions and either the 1-mm/2nd-order
      refractions or the 6-mm/4th-order refractions were compared. The results suggest
      that, for determining refractions based on wave aberration data with large
      pupils, similar results occur by either restricting the analysis to second-order
      Zernike aberrations with a smaller pupil such as 3 mm or using both second- and
      fourth-order Zernike aberrations. Since subjective refraction is largely
      independent of the pupil size under photopic conditions, objective refractions
      based on either of these analyses may be the most useful.

PMID- 12801165
TI  - Integration of first- and second-order orientation.
AB  - The problem of how visual information such as orientation is combined across
      space bears on key visual abiities, such as texture perception. Orientation
      signals can be derived from both luminance and contrast, but it is not well
      understood how such information is pooled or how these different orientation
      signals interact in the integration process. We measured orientation
      discrimination thresholds for arrays of equivisible first-order and second-order
      Gabors. Thresholds were measured as the orientation variability in the arrays
      increased, and we estimated the number of samples (or efficiency) and internal
      noise of the mechanism being used. Observers were able to judge the mean
      orientation of arrays of either first- or second-order Gabors. For arrays of
      first-order and arrays of second-order Gabors, estimates of the number of samples
      used increased as the number of Gabors increased. When judging the orientation of
      arrays of either order, observers were able to ignore randomly oriented Gabors of
      the opposite order. If observers did not know which Gabor type carried the more
      useful orientation information, they tended to use the information from first
      order Gabors (even when this was poorer information). Observers were unable to
      combine information from first- and second-order Gabors, though this would have
      improved their performance. The visual system appears to have separate
      integrators for combining local orientation across space for luminance- and
      contrast-defined features.

PMID- 12801166
TI  - Illumination direction from texture shading.
AB  - We investigate the ability of human observers to judge the direction of
      illumination from image texture. Photographs of 61 real surfaces were used, taken
      from the Columbia-Utrecht Reflectance and Texture (Curet) database
      (http:/www.cs.columbia.edu/CAVE/curet). All samples were normally viewed but
      obliquely illuminated, the elevation of the source being 22.5 degrees, 45.0
      degrees, or 67.5 degrees. The illumination was with a collimated, parallel beam.
      Stimuli were presented in random orientation, and observers had to judge both the
      elevation and the azimuth of the source. Observers judged the azimuth within
      approximately 15 degrees, except for the fact that they committed random (with
      approximately 50% probability) sign flips (180 degrees flips). Connected with
      this finding is the fact that observers judged the illumination to be from above
      rather than below in the overwhelming majority of cases, despite the fact that
      each case occurred with equal probability. The elevation of the illumination can
      be judged to some extent but is not far above chance level. The data are in good
      agreement with a simple model that bases the estimate of illumination direction
      on the second-order statistics of local luminance gradients. This locates the
      locus of the probable mechanism very early in the visual stream.

PMID- 12801167
TI  - Effects of focusing on the resolution characteristics of integral photography.
AB  - The effects of focusing on the resolution characteristics of integral photography
      (IP) are analyzed. First, there is an attempt to obtain the resolution
      characteristics of capture and display systems as the product of their modulation
      transfer functions (MTFs). Next, the relationship between this overall MTF and
      focusing during the capture is studied. The results show that, with focusing set
      at infinity, IP can provide three-dimensional images without remarkable
      resolution degradation over a wide range of depth.

PMID- 12801168
TI  - Nonparaxial model for the focusing of high-numerical-aperture photon sieves.
AB  - Recently, a paraxially individual far-field model was presented for the focusing
      and imaging analysis of pinhole photon sieves. By use of a local Taylor expansion
      of the integrated function of the Rayleigh-Sommerfeld diffraction formula, the
      small-size property of the individual pinholes, and the linear superposition
      principle, we extend this model to the nonparaxial case of high-numerical
      aperture photon sieves. Some related problems, such as the validity range of this
      nonparaxial model and the selection conditions for the individual pinholes, are
      also discussed in detail.

PMID- 12801169
TI  - Rapidly convergent phase-retrieval strategy for use with reflected laser light.
AB  - An approach for wave-front sensing using reflected laserlight from a rough object
      is proposed. Light from a single laser beam is split into two beams, and the
      beams are launched from spatially separated apertures to illuminate an object.
      The reflected laser light is measured in the pupil plane of a receive telescope
      and in a plane conjugate to the object. By modulation of one of the two
      illuminator beams, the intensity pattern associated with each beam, as well as
      the field cross product of the two beams, is measured in each plane. A phase
      retrieval algorithm is formulated by using projections onto constraint sets to
      recover the complex field associated with each illuminator. The algorithm is
      found to converge rapidly to the correct solution, particularly when compared
      with the convergence rates of more conventional phase-retrieval approaches. The
      new algorithm exhibits excellent performance in strong scintillation and is very
      tolerant to noise, exhibiting only a very small noise gain.

PMID- 12801170
TI  - Hybrid projection-reflection method for phase retrieval.
AB  - The phase-retrieval problem, fundamental in applied physics and engineering,
      addresses the question of how to determine the phase of a complex-valued function
      from modulus data and additional a priori information. Recently we identified two
      important methods for phase retrieval, namely, Fienup's basic input-output and
      hybrid input-output (HIO) algorithms, with classical convex projection methods
      and suggested that further connections between convex optimization and phase
      retrieval should be explored. Following up on this work, we introduce a new
      projection-based method, termed the hybrid projection-reflection (HPR) algorithm,
      for solving phase-retrieval problems featuring nonnegativity constraints in the
      object domain. Motivated by properties of the HPR algorithm for convex
      constraints, we recommend an error measure studied by Fienup more than 20 years
      ago. This error measure, which has received little attention in the literature,
      lends itself to an easily implementable stopping criterion. In numerical
      experiments we found the HPR algorithm to be a competitive alternative to the HIO
      algorithm and the stopping criterion to be reliable and robust.

PMID- 12801171
TI  - Marginal estimation of aberrations and image restoration by use of phase
      diversity.
AB  - We propose a novel method called marginal estimator for estimating the
      aberrations and the object from phase-diversity data. The conventional estimator
      found in the literature concerning the technique first proposed by Gonsalves has
      its basis in a joint estimation of the aberrated phase and the observed object.
      By means of simulations, we study the behavior of the conventional estimator,
      which is interpretable as a joint maximum a posteriori approach, and we show in
      particular that it has undesirable asymptotic properties and does not permit an
      optimal joint estimation of the object and the aberrated phase. We propose a
      novel marginal estimator of the sole phase by maximum a posteriori. It is
      obtained by integrating the observed object out of the problem. This reduces
      drastically the number of unknowns, allows the unsupervised estimation of the
      regularization parameters, and provides better asymptotic properties. We show
      that the marginal method is also appropriate for the restoration of the object.
      This estimator is implemented and its properties are validated by simulations.
      The performance of the joint method and the marginal one is compared on both
      simulated and experimental data in the case of Earth observation. For the studied
      object, the comparison of the quality of the phase restoration shows that the
      performance of the marginal approach is better under high-noise-level conditions.

PMID- 12801172
TI  - Phase reconstruction from intensity measurements in linear systems.
AB  - The phase of a signal at a plane is reconstructed from the intensity profiles at
      two close parallel screens connected by a small abcd canonical transform; this
      applies to propagation along harmonic and repulsive fibers and in free media. We
      analyze the relationship between the local spatial frequency (the signal phase
      derivative) and the derivative of the squared modulus of the signal under a one
      parameter canonical transform with respect to the parameter. We thus generalize
      to all linear systems the results that have been obtained separately for Fresnel
      and fractional Fourier transforms.

PMID- 12801173
TI  - Absorption in multiple-scattering systems of coated spheres.
AB  - We derive formulas for rigorous transfer matrix calculations of absorption in
      multiple-coherent-scattering systems in which the scatterers are multiply coated
      spheres (not necessarily concentric). Any of the spherical coatings, cores, or
      host media may be composed of absorbing materials. For a nonabsorbing host media,
      the total absorption may be deduced from overall energy conservation. A more
      detailed description of the absorption is obtained through formulas yielding the
      absorption within individual scatterers and/or coatings. We present some
      illustrative applications of these formulas to the design of heterogeneous coated
      sphere media exhibiting enhanced absorption.

PMID- 12801174
TI  - Simulation of depolarization effect by a rough surface for spectroscopic
      ellipsometry.
AB  - We employed the integral equation method (IEM) to simulate optical scattering by
      a randomly rough surface for spectroscopic ellipsometry. An explicit Mueller
      matrix expression of the IEM for single scattering by moderately small surface
      roughness makes it possible to calculate the depolarization effect. The IEM
      allows a relatively rigorous assessment of the surface-scattering effect in a
      wide spectral range.

PMID- 12801175
TI  - Resolution of synthetic-aperture imaging through turbulence.
AB  - A theory is developed for the resolution of an optical synthetic-aperture imaging
      system viewing an object through an inhomogeneous refractive medium. The
      inhomogeneities of the propagation medium create errors in the phase history data
      with resultant space-variant image effects, including geometric distortions and
      broadening of the impulse response or point-spread function. I relate the
      intensity-impulse response to the usual wave structure function. I determine the
      modulation transfer function for synthetic apertures of any size and exposure
      time, valid whenever the optical bandwidth is small compared with the carrier
      frequency, and derive the resolution for monostatic and bistatic synthetic
      apertures, valid whenever the real sampling aperture is small compared with the
      medium's coherence length. The results take the same form as the well-known
      turbulence-limited resolution of incoherent, real-aperture imaging with short
      exposure. Turbulence-limited synthetic-aperture resolution is somewhat better
      than incoherent real-aperture resolution under the same conditions. Autofocus
      processing improves synthetic-aperture resolution beyond this limit, and adaptive
      correction of higher-order phase history errors would improve it further.

PMID- 12801176
TI  - Local, hierarchic, and iterative reconstructors for adaptive optics.
AB  - Adaptive optics systems for future large optical telescopes may require thousands
      of sensors and actuators. Optimal reconstruction of phase errors using relative
      measurements requires feedback from every sensor to each actuator, resulting in
      computational scaling for n actuators of n2. The optimum local reconstructor is
      investigated, wherein each actuator command depends only on sensor information in
      a neighboring region. The resulting performance degradation "global" modes is
      quantified analytically, and two approaches are considered for recovering global
      performance. Combining local and global estimators in a two-layer hierarchic
      architecture yields computations scaling with n(4/3); extending this approach to
      multiple layers yields linear scaling. An alternative approach that maintains a
      local structure is to allow actuator commands to depend on both local sensors and
      prior local estimates. This iterative approach is equivalent to a temporal low
      pass filter on global information and gives a scaling of n(3/2). The algorithms
      are simulated by using data from the Palomar Observatory adaptive optics system.
      The analysis is general enough to also be applicable to active optics or other
      systems with many sensors and actuators.

PMID- 12801177
TI  - Mode analysis of spreading of partially coherent beams propagating through
      atmospheric turbulence.
AB  - The spreading of partially coherent beams propagating through atmospheric
      turbulence is studied by use of the coherent-mode representation of the beams.
      Specifically, we consider partially coherent Gaussian Schell-model beams entering
      the atmosphere, and we examine the spreading of each coherent mode, represented
      by a Hermite-Gaussian function, on propagation. We find that in atmospheric
      turbulence the relative spreading of higher-order modes is smaller than that of
      lower-order modes, whereas the relative spreading of all order modes is the same
      as in free space. This modal behavior successfully explains why under certain
      circumstances partially coherent beams are less affected by atmospheric
      turbulence than are fully spatially coherent laser beams.

PMID- 12801179
TI  - Decentered elliptical Hermite-Gaussian beam.
AB  - A new kind of laser beam called the decentered elliptical Hermite-Gaussian beam
      (DEHGB) is defined by use of a tensor method. The propagation formula of the
      DEHGB passing through a nonsymmetrical paraxial optical system is derived through
      vector integration. The derived formula can be easily reduced to the propagation
      formula of an aligned elliptical Hermite-Gaussian beam and that of a decentered
      elliptical Gaussian beam under certain conditions. By use of this formula, the
      propagation characteristics of the DEHGB through free space are presented
      graphically. As application examples, we construct a generalized laser array
      using the DEHGB as the fundamental mode. We also obtain the decentered elliptical
      flattened Gaussian beam by expressing it as superposition of a series of DEHGBs
      by using polynomial expansion.

PMID- 12801178
TI  - Iterative boundary method for diffuse optical tomography.
AB  - The recent application of tomographic methods to three-dimensional imaging
      through tissue by use of light often requires modeling of geometrically complex
      diffuse-nondiffuse boundaries at the tissue-air interface. We have recently
      investigated analytical methods to model complex boundaries by means of the
      Kirchhoff approximation. We generalize this approach using an analytical
      approximation, the N-order diffuse-reflection boundary method, which considers
      higher orders of interaction between surface elements in an iterative manner. We
      present the general performance of the method and demonstrate that it can improve
      the accuracy in modeling complex boundaries compared with the Kirchhoff
      approximation in the cases of small diffuse volumes or low absorption. Our
      observations are also contrasted with exact solutions. We furthermore investigate
      optimal implementation parameters and show that a second-order approximation is
      appropriate for most in vivo investigations.

PMID- 12801180
TI  - Looking into the water with oblique head tilting: revision of the aerial
      binocular imaging of underwater objects.
AB  - It is a well-known phenomenon that when we look into the water with two aerial
      eyes, both the apparent position and the apparent shape of underwater objects are
      different from the real ones because of refraction at the water surface. Earlier
      studies of the refraction-distorted structure of the underwater binocular visual
      field of aerial observers were restricted to either vertically or horizontally
      oriented eyes. We investigate a generalized version of this problem: We calculate
      the position of the binocular image point of an underwater object point viewed by
      two arbitrarily positioned aerial eyes, including oblique orientations of the
      eyes relative to the flat water surface. Assuming that binocular image fusion is
      performed by appropriate vergent eye movements to bring the object's image onto
      the foveas, the structure of the underwater binocular visual field is computed
      and visualized in different ways as a function of the relative positions of the
      eyes. We show that a revision of certain earlier treatments of the aerial imaging
      of underwater objects is necessary. We analyze and correct some widespread
      erroneous or incomplete representations of this classical geometric optical
      problem that occur in different textbooks. Improving the theory of aerial
      binocular imaging of underwater objects, we demonstrate that the structure of the
      underwater binocular visual field of aerial observers distorted by refraction is
      more complex than has been thought previously.

PMID- 12801181
TI  - Theoretical evaluation of the Brillouin threshold and the steady-state Brillouin
      equations in standard single-mode optical fibers.
AB  - We first use the nonlocalized, fluctuating source model for the stimulated
      Brillouin scattering to get the exact spectrum of the Stokes wave in optical
      fibers with attenuation loss. A new relation for the evaluation of the critical
      pump power (or Brillouin threshold) depending on the fiber length is then
      introduced, which should be more precise than the well-known Smith formula.
      Furthermore, we give for the first time, to the best of our knowledge, an
      approximate solution for standard steady-state Brillouin equations, which
      consists of two simple relations.

PMID- 12801182
TI  - WAIS-III factor index score patterns after traumatic brain injury.
AB  - Profile subtypes, based on the Wechsler Adult Intelligence Scale-Third Edition
      (WAIS-III) factor index scores, were examined in a sample of 166 patients with
      traumatic brain injury (TBI) by means of a two-stage clustering procedure. Three
      reliable subtypes were found that were differentiated primarily by level of
      performance across all factor index scores, although each of them demonstrated a
      relative weakness on the Processing Speed index. These subtypes were then
      validated on the basis of demographic variables, injury parameters, and
      additional psychometric measures that had not been included in the clustering
      procedures. The results indicated that performance on the WAIS-III after TBI was
      affected by both injury severity and level of education. It is concluded that
      there is no unique "signature" profile on the WAIS-III after TBI, except that a
      relative strength on the Processing Speed index is uncommon with this condition.

PMID- 12801183
TI  - Refinement of the MMPI-2 F(p) scale is not necessary: a response to Gass and
      Luis.
AB  - Gass and Luis (2001) reported that four MMPI-2 Lie scale items contained on the
      F(p) scale do not measure symptom exaggeration but measure defensiveness. They
      hold that elimination of the four Lie scale items improves the utility of the
      F(p) scale in the identification of exaggeration in VA samples. To directly
      address the assertion that removal of the L scale items from the F(p) scale
      enhances the predictive validity of F(p), data derived from a previously
      published study where 74 psychiatric inpatients were asked to retake the MMPI-2
      and either feign psychopathology or respond in an honest manner were reanalyzed.
      The intact F(p) scale demonstrated a stronger correlation with group membership,
      increased incremental validity, and superior classification rates compared with
      the F(p) scale without the 4 Lie scale items. Consequently, the F(p) refinement
      recommended by Gass and Luis is unnecessary.

PMID- 12801184
TI  - The diagnosis of neurological disorders in older adults.
AB  - Are neurological disorders overdiagnosed in older adults? Previous reports
      suggest that age bias may lead to diagnostic inaccuracies for older adult
      clients. In the present study, the average test scores for community-dwelling 38
      year-old and 74-year-old individuals were presented as the results for a 38-year
      old client and a 74-year-old client, respectively. Neuropsychologists did not
      make diagnoses of neurological disorder or dementiafor either of the clients. The
      results from this study indicate that age bias is not as serious a problem among
      neuropsychologists as many psychologists once believed.

PMID- 12801185
TI  - Therapeutic reactance in a depressed client sample: a comparison of two measures.
AB  - The impact of client variables on psychotherapy is of both theoretical and
      practical importance. Reactance--the premise that individuals seek to maintain
      control over personal freedoms when threatened by a perceived loss thereof--has
      been shown to have an impact on the effectiveness of therapeutic interventions.
      Developing an effective means of quantitatively assessing this characteristic
      prior to treatment could facilitate treatment planning and maximize treatment
      outcome. The present study compared two paper-and-pencil measures of reactance:
      the Therapeutic Reactance Scale (TRS) and Resistance Potential (RP). Ninety-eight
      men and women diagnosed with depression completed both measures. The TRS and RP
      failed to correlate despite their presumed ability to measure the same construct.
      The RP exhibited extremely poor internal consistency, calling into question
      results that have been based on this measure. The TRS results provided evidence
      of convergent, divergent, and construct validity for this instrument.

PMID- 12801186
TI  - The antisocial process screening device: an examination of its construct and
      criterion-related validity.
AB  - The clinical assessment of psychopathy in adulthood is well established via
      programmatic research. More recently, psychopathy has been extended to children
      and adolescents with correlates to maladaptive personality traits, violent
      behavior, and noncompliance with institutional rules. To screen for adolescent
      psychopathy, the Antisocial Process Screening Device (APSD) was developed as a 20
      item self-report measure of psychopathy. The original validation of the APSD was
      limited to samples of clinic-referred and community-based children. In extending
      this research to delinquent populations, the current article uses two separate
      samples of adolescent offenders incarcerated in a maximum security facility (n =
      78) and a local juvenile detention facility (n = 77). As evidence of criterion
      related validity, the APSD was compared with two versions of the Psychopathy
      Checklist that yielded mixed results. Construct validity was examined via a
      confirmatory factor analysis that provided support for a three-factor model of
      the APSD.

PMID- 12801187
TI  - Scoring reliability on the Wechsler Adult Intelligence Scale-Third Edition (WAIS
      III).
AB  - Nineteen psychologists and 19 graduate students scored two Wechsler Adult
      Intelligence Scale-Third Edition patient protocols. Mean IQs and indexes were
      similar across groups, but the ranges for Verbal IQ (VIQ), Performance IQ (PIQ),
      and Full Scale IQ (FSIQ) on one protocol were 25, 22, and 11 points,
      respectively. For both protocols taken together, percentages of agreement with
      the "actual" IQs for psychologists were only 26.3 for VIQ, 36.8 for PIQ, and 42.1
      for FSIQ. For students, percentages were 15.8 for VIQ, 23.7 for PIQ, and 31.6 for
      FSIQ. The percentages of FSIQs that fell within +/- 1 standard error of
      measurement of the actual IQs were 89.5 for psychologists and 76.3 for students.
      Scoring error also had a negative impact on index scores. Both groups were
      confident about their scoring accuracy.

PMID- 12801188
TI  - Detection of feigned mental disorders: a meta-analysis of the MMPI-2 and
      malingering.
AB  - The validity of test data from multiscale inventories is dependent on self
      reports that may be easily distorted by malingering. In examining the Minnesota
      Multiphasic Personality Inventory-2's (MMPI-2) role in the assessment of
      feigning, this review provides a conceptual analysis of the detection strategies
      underlying the MMPI-2 validity scales. The conceptual analysis is augmented by
      comprehensive meta-analysis of 65 MMPI-2 feigning studies plus 11 MMPI-2
      diagnostic studies. For the rare-symptoms strategy, Fp (Cohen's d = 2.02) appears
      especially effective across diagnostic groups; its cut scores evidence greater
      consistency than most validity indicators. The data supported the F as an
      effective scale but questioned the routine use of Fb. Among the specialized
      scales, Ds appeared especially useful because of its sophisticated strategy,
      consistent cut score, and minimalfalse-positives. General guidelines are
      offeredfor specific MMPI-2 validity scales in the assessment of malingering with
      specific diagnoses.

PMID- 12801189
TI  - The Abbreviated Math Anxiety Scale (AMAS): construction, validity, and
      reliability.
AB  - Psychometric properties of mathematics anxiety measures have not adequately been
      studied. Using a large sample size (N = 1,239), the authors developed an
      abbreviated math anxiety measure, examined its psychometric properties, and
      assessed the generalizability of the model across samples. Exploratory factor
      analysis yielded a nine-item measure and strong internal consistency, test-retest
      reliability, and good convergent/divergent validity was demonstrated with an
      independent sample. When administered to a replication sample, indexes suggested
      an excellent model fit. TheAbbreviated Math Anxiety Scale (AMAS) may represent a
      more parsimonious and valid approach to assess mathematics anxiety.

PMID- 12801190
TI  - Characterizing aggressive behavior.
AB  - In the research literature, aggressive behavior has traditionally been classified
      into two distinct subtypes, impulsive or premeditated. Impulsive aggression is
      defined as a hair-trigger aggressive response to provocation with loss of
      behavioral control. Premeditated aggression is defined as a planned or conscious
      aggressive act, not spontaneous or related to an agitated state. The present
      study outlines the development of a clinically useful self-report instrument, the
      Impulsive/Premeditated Aggression Scales (IPAS), designed to characterize
      aggressive behavior as predominately impulsive or predominately premeditated in
      nature. The IPAS showed strong reliability and validity. Analysis of the
      IPASscores demonstrated thepresence of two types of aggressive behavior,
      impulsive and premeditated, in men referred for anger problems. The aggression of
      most individuals in the present sample was characterized as predominately
      impulsive in nature (90%).

PMID- 12801191
TI  - Incremental validity of the MMPI-A content scales in a residential treatment
      facility.
AB  - The current study explores the incremental validity of the Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-A) content scales. Participants were 335
      adolescents (250 boys and 85 girls) between the ages of 13 and 18 who were
      receiving mental health services from a residential treatment facility.
      Regression analyses were conducted to identify the amount of additional variance
      accounted for by the content scales over the clinical scales in predicting scores
      on a clinician rating form of psychological symptomatology. Several of the MMPI-A
      content scales demonstrated significant incremental validity above the clinical
      scales in predicting clinician ratings of adolescents' behavior and personality
      characteristics. The clinical scales also demonstrated incremental validity in
      reference to the content scales, indicating then that the two sets of scales
      provide complementary information. Magnitude of the additional criterion variance
      predicted was modest.

PMID- 12801192
TI  - High-tech, low touch.

PMID- 12801193
TI  - Evaluation of the fibular incisura of the tibia with magnetic resonance imaging.
AB  - Knowledge of the distal tibiofibular syndesmosis should be helpful in determining
      the normal position of the fibula in the incisural notch. The purpose of this
      study was to determine the anatomic characteristics of the fibular incisura of
      the tibia on MR imaging. One hundred fifty lower limbs (43 male, 32 female
      volunteers) were examined with MRI. The length of the anterior facet was 10.4 mm
      in males and 8.9 mm in females, and the length of the posterior facet was 10.4 mm
      in males and 8.9 mm in females. The angle between anterior and posterior facets
      was 138.6 degrees in males and 139.9 degrees in females. The depth of the fibular
      incisura of the tibia was 3.6 mm in males and 2.9 mm in females. The vertical
      distance of tibiofibular overlapping was 7.9 mm in males and 7.0 mm in females.
      The distance between anterior margin of the tibia and anterior margin of the
      fibula was 14.3 mm in males and 12.5 mm in females. All of these parameters of
      men (except the angle between anterior and posterior facets) were significantly
      higher than the parameters of women (p<.001, p<.001, p<.05, p<.05, p<.01,
      respectively).

PMID- 12801194
TI  - Peroneus longus ligamentoplasty for chronic instability of the distal
      tibiofibular syndesmosis.
AB  - The distal tibiofibular syndesmosmotic ligament complex is important for dynamic
      stability and congruency of the ankle joint. Syndesmotic lesions in the ankle
      fracture-dislocations are well recognized and classified systematically. Chronic
      insufficiency of the syndesmosis leads to a lateral shift of the talus and under
      eversion stress permits a pathological rotation of the talus. There is also
      retroversion of the distal fibula representing a painful deformity. Little
      experience exists with surgical reconstruction of the syndesmosis. This article
      describes a new ligamentoplasty with a split peroneus longus tendon graft that
      mimics the normal anatomic conditions of the syndesmotic complex in 16 patients
      with symptomatic chronic syndesmotic insufficiency after pronation-external
      rotation and pronation abduction injuries to the ankle joint. Postoperatively, no
      infections or hematomas were seen. One patient had asymptomatic breakage of the
      syndesmosis screw; one patient had a 10 degree decrease of dorsiflexion at the
      ankle because of a partial anterior tibiofibular synostosis. Fifteen of 16
      patients had pain relief at a mean follow-up period of 16.4 months (range, 13-29
      months); all patients had relief of the chronic swelling of the ankle and the
      giving way. The mean Karlsson score at follow-up was 88 (range, 70-100) points.
      It may be concluded that peroneus longus ligamentoplasty in a preliminary series
      resulted in reliable ankle stability and considerable pain relief in patients
      with chronic syndesmotic instability.

PMID- 12801196
TI  - Role of passive structures in the mobility and stability of the human subtalar
      joint: a literature review.
AB  - The subtalar joint plays a fundamental role in the transmission of loads between
      the leg and the foot. Although anatomical structures of this joint have been
      described extensively, much ambiguity about their location, shape, and function
      still persists. There is also disagreement regarding mobility, for example,
      whether the joint can be considered a hinge, screw-like, or a multiaxial joint.
      The most relevant studies from the literature are reported and the main
      experimental observations discussed. Recent studies have described the subtalar
      joint as a structure with no degrees of unresisted freedom, i.e., motion from the
      single neutral position is attained only by deformation of the ligaments and of
      the articular surfaces.

PMID- 12801195
TI  - Cold weather training: a risk factor for Achilles paratendinitis among recruits.
AB  - In a prospective study of risk factors for Achilles tendinopathy among four
      induction cycles of infantry recruits, 95 out of 1405 recruits, (6.8%) were found
      to suffer from Achilles tendinopathy. In more than 94% of the cases, the
      tendinopathy was considered to be paratendinitis. Training season had a
      statistically significant effect on the incidence of Achilles paratendinitis with
      3.6% suffering in the summer and 9.4% in the winter (p = .001). This increased
      risk for Achilles paratendinitis in cold weather outdoor training can be
      explained by a fall in temperature of the Achilles paratenon whose membranes are
      rich in mucopolysaccharides and serve as a lubricant for gliding of the tendon
      and epitenon. Decreased temperature may increase the viscosity of the lubricant
      and thereby increases friction and risk for Achilles paratendinitis. This same
      relationship illustrates why "warming up" before exercising may be important in
      lowering the incidence of Achilles paratendinitis.

PMID- 12801197
TI  - Dual-function foot orthosis: effect on shock and control of rearfoot motion.
AB  - Orthoses have been designed that claim to both reduce shock and control rearfoot
      motion. It was hypothesized that the dual-purpose soft orthosis would reduce
      shock and control rearfoot motion greater than a no-orthotic condition. Three
      dimensional kinematic and kinetic data were collected along with tibial
      acceleration while subjects ran in no-orthotic, the dual-purpose orthotic, and a
      rigid orthotic condition. Variables of interest were eversion excursion, peak
      eversion, eversion velocity, peak positive acceleration, loading rate, and leg
      stiffness. None of the evaluated variables were significantly different (p = .05)
      between the three conditions. These data suggest that shock attenuation and
      rearfoot motion cannot be controlled by the orthoses used in this study for a
      group of healthy runners.

PMID- 12801198
TI  - Return to activity after sesamoidectomy in athletically active individuals.
AB  - Sesamoidectomy of the first metatarsophalangeal joint in athletically active
      patients may be indicated in cases of chronic sesamoiditis resistant to
      nonsurgical care or symptomatic displaced fractures or nonunion. Painful scar,
      hallux deviation, and delayed return to activity are all potential complications.
      These need to be considered especially when performing surgery in the
      athletically active individual. Twenty-six sesamoidectomies in 24 patients (21
      females and 3 males) were reviewed for type of sesamoidectomy, incision location,
      time to return to activity, and complications. Mean age was 35.4 years (range, 16
      68 years) with mean follow-up 86.4 months. Eleven athletes (defined as
      professional or varsity level sports) operated on had a mean return to activity
      of 7.5 weeks (range, 4-10 weeks), while 13 "active" patients had a mean return to
      activity of 12.0 weeks. This difference was statistically significant using the t
      test, (p < .02). There were 10 fibular and 16 tibial sesamoids excised.
      Complications included one hallux varus and two cases of postoperative scarring
      with neuroma-like symptoms, all associated with fibular sesamoidectomy; there was
      one case of hallux valgus deformity with tibial sesamoidectomy. Despite the
      functional importance of tibial and fibular sesamoids, athletically active
      individuals can return to sports after a sesamoidectomy as early as 7.5 weeks.

PMID- 12801199
TI  - Limb salvage: the infected retrograde tibiotalocalcaneal intramedullary nail.
AB  - Tibiotalocalcaneal arthrodesis utilizing a retrograde intramedullary nail has
      been used for nearly a decade. The indications for retrograde intramedullary
      nailing to achieve a tibiotalocalcaneal arthrodesis have expanded from systemic
      arthritides and post-traumatic arthritis to use in diabetic patients with severe
      Charcot neurarthropathy and hindfoot malalignment. Results with this procedure
      have been good, with low infection rates when used in nonimmunocompromised hosts.
      As indications have expanded to include diabetic deformities, infection rates may
      increase. We report on the results of a salvage technique and management plan
      utilized in the treatment of infected tibiotalocalcaneal arthrodesis in five high
      risk (immunocompromised) patients. The majority of these patients had diabetes
      with Cierny-Mader IVB osteomyelitis, and would have required an above-knee or
      below-knee amputation due to their infection.

PMID- 12801200
TI  - A biomechanical evaluation of the tibiofibular and tibiotalar ligaments of the
      ankle.
AB  - The purpose of this ex vivo biomechanical study was to determine the strength and
      stiffness of the anterior and posterior syndesmotic tibiofibular ligaments and
      the posterior tibiotalar component of the deltoid ligament. Injuries to these
      ligaments are a prevalent clinical problem, yet little is known about their
      mechanical behavior. Ten fresh-frozen cadaver lower extremities (average age at
      death, 72 +/- 8 years) were harvested. The anterior and posterior tibiofibular
      ligaments and the posterior tibiotalar component of the deltoid were isolated and
      prepared as bone-ligament-bone complexes for tensile testing to determine
      strength, stiffness, and mode of failure. The posterior tibiofibular ligament
      exhibited greater strength, but not significantly so (p < .05), than the anterior
      tibiofibular ligament and the posterior tibiotalar component of the deltoid
      ligament. There were no significant differences in stiffness between the three
      ligaments tested. The dominant mode of failure for the anterior tibiofibular
      ligament was ligament substance rupture, primarily near its fibular insertion,
      whereas the failure modes of the posterior tibiofibular ligament were evenly
      split between substance ruptures and fibular avulsions. The posterior tibiotalar
      component of the deltoid ligament ruptured most often near the talar insertion.
      The tibiofibular ligaments showed greater strength than the lateral collateral
      and deltoid ligaments, as mentioned in literature. The greater strength of the
      tibiofibular ligaments relative to the lateral collateral and deltoid ligaments
      suggests that these ligaments play an important role in ankle constraint.

PMID- 12801201
TI  - Anatomical reconstruction of the spring ligament using peroneus longus tendon
      graft.
AB  - Posterior tibial tendon insufficiency is often associated with failure of the
      spring ligament and flatfoot deformity. Arch correction procedures involving bony
      realignment, such as lateral column lengthening or joint fusions, can predispose
      to arthritis. Soft tissue reconstruction may provide a more anatomical correction
      without these complications. The purpose of this investigation was to compare the
      ability of three different spring ligament reconstruction procedures to correct
      flatfoot deformity. A deformity model of 5 degrees - 15 degrees talonavicular
      abduction was created in 10 cadaver foot-ankle specimens. Three reconstructions
      utilizing the peroneus longus tendon were evaluated for their ability to correct
      talonavicular abduction and subtalar eversion under 357 N vertical GRF load. A
      superomedial/plantar passage of the tendon through the calcaneus and navicular
      was shown to be more effective than either of the other two approaches,
      correcting the talonavicular joint from 9.1 degrees +/- 8.1 degrees abducted to
      1.0 degree +/- 6.8 degrees adducted, and the subtalar joint from 3.1 degrees +/-
      3.3 degrees everted to 0.4 degrees +/- 4.2 degrees inverted. Thus, an anatomical
      reconstruction of a model of a failed spring ligament was demonstrated to be
      effective in the correction of a flatfoot deformity produced in cadaver foot
      ankle specimens.

PMID- 12801202
TI  - The piano key test: a clinical sign for the identification of subtle
      tarsometatarsal pathology.

PMID- 12801203
TI  - Achilles tendon ruptures: functional outcome of surgical repair with a "pull-out"
      wire.
AB  - This is a retrospective review of 30 consecutive patients with acute Achilles
      tendon ruptures treated surgically by a single surgeon between 1992 and 1999.
      Repair was effected with a 26-gauge "pull-out" wire technique. A compressive
      dressing reinforced with plaster was employed to immobilize the ankle in neutral
      for 6 weeks. The hardware was removed 6 weeks postoperatively under local
      anesthesia. Intensive physical therapy was employed until ankle motion was
      symmetric and single heel raise was possible. Average follow-up was 4 years
      (range, 1-8 years). Nearly all patients (29/30) report satisfaction with their
      outcome. Most patients (29/30) had AOFAS Ankle-Hindfoot Scores greater than 90.
      Twenty-three (77%) returned to preoperative levels of athletic activities.
      Isometric testing documented 81% plantarflexion strength compared to the normal
      ankle at a mean of 32 months postoperatively. Five of eight women reported shoe
      wear difficulties related to the incision. There were no reruptures or deep
      infections. The "pull-out" wire technique is recommended for patients who wish to
      return to an active lifestyle. This method provides rigid approximation of tendon
      length, minimizes strangulation of tissue, repairs large gaps, and avoids late
      foreign-body reactions.

PMID- 12801204
TI  - Pressure distribution patterns under the feet of new walkers: the first two
      months of independent walking.
AB  - In order to describe foot function during the first weeks of independent walking,
      spatio-temporal pressure distribution patterns were measured. These data give
      detailed information about roll-off of the foot, by determining the course of the
      center of pressure, and about load bearing, by calculating relative vertical
      impulses under the feet. During those first weeks of independent walking, roll
      off is very unstable. Although infants can occasionally perform a mature roll
      off, a consistent pattern has not yet developed and there is instability. To
      improve stability the entire plantar surface area contributes to load bearing-
      first, because a larger contact area will improve stability, and second, because
      a forward shifting of the load allows more muscular control to compensate for
      minor imbalances under the foot.

PMID- 12801205
TI  - The relationship between professional tournament structure on the national level
      and success in men's professional tennis.
AB  - This article discusses the relationship between a nation's men's professional
      tennis tournament structure and that nation's success in the international men's
      game. The 2002 men's professional tennis tournament calendar provided the
      distribution of events on the top thirty nations. Criteria for a nation's success
      in men's professional tennis were: nation's number of players with ATP points,
      nation's number of players in the top 200 ranking, and the combined ATP ranking
      of a nation's top 5 male players. Pearson correlations were performed between the
      number of tournaments and each criterion. Results showed a considerable variation
      in the number of events ranging between 67 (United States) and 4 (Sweden). On the
      other hand, 29 of the 30 countries had Internationally ranked male player/s and
      22 had player/s ranked inside the top 200. Results also showed that: 1. nations
      with a high number of men's professional events are best positioned to provide
      for more professionally ranked players, 2. nations with more professional men's
      tournaments are likely to experience success in the men's international game, and
      3. having a high number of tournaments is not a prerequisite to having a group of
      players ranked among the game's elite. It can be concluded that competition is an
      important factor in player development and that countries who want to be
      successful at the professional level should try to provide best competitive
      progression for their players.

PMID- 12801206
TI  - Medical assistance at the Brazilian juniors tennis circuit--a one-year
      prospective study.
AB  - A prospective study was conducted during one year to evaluate injuries in
      Brazilian Junior tennis players during the national circuit, in 2001. Male and
      female athletes in the age categories under 12, under 14, under 16 and under 18
      years, all members of The Brazilian Tennis Confederation, participated in the
      study. Two physiotherapists and/or one physician evaluated the athletes. A total
      of 280 medical examinations were performed in 151 tennis players who needed
      medical treatment during the tournaments. The 151 athletes had 1-6 medical
      treatments during the tournaments and the mean was 1.8 treatment per athlete. The
      overall incidence was 6.9 medical treatments for every 1,000 games played.
      Medical assistance tothe athletes was performed on court in 83 (29.6%) occasions,
      185 (66.1%) at the medical department and in both in 12 (4.3%) occasions.
      Retirement of the match was reported in 9 (3.2%) lesions. The most frequent
      injuries were: muscle contractures (76 - 27.14%), muscle pain/fatigue (36
      12.85%), muscle strain (35-12.52%), tendinopathies (20 - 7.14%), cramps (16 
      5.71%), ankle sprain (12 -4.28%) and low back pain (10-3.57%). Muscle pathology
      was the major source of injuries causing the athlete to seek medical assistance.
      Preventative measures are important to reduce the number of injuries, which may
      include muscle stretching programs and adequate nutrition and hydration.

PMID- 12801207
TI  - Heat cramps: fluid and electrolyte challenges during tennis in the heat.
AB  - Sweat losses during tennis can be considerable. And while most players make a
      genuine effort to stay well hydrated to maintain performance and reduce the risk
      of heat illness, regular and copious water intake is often not enough. Besides an
      extraordinary water loss, extensive sweating can lead to a concomitant large
      electrolyte deficit too--particularly for sodium. Although a variety of other
      mineral deficiencies and physiological conditions are purported to cause muscle
      cramps, evidence suggests that, when a tennis player cramps in warm to hot
      weather, extensive and repeated sweating during the current and previous matches
      and a consequent sodium deficit are usually the primary contributing factors.
      Heat cramps often begin as subtle "twitches" or fasciculations in one or more
      voluntary muscles and, unless treated, can rapidly progress to widespread
      debilitating muscle spasms that leave an afflicted player on the court writhing
      in pain. If sufficient preventive measures are taken well before and during play,
      such cramping is avoidable in most cases. Appropriate and sufficient salt and
      fluid intake will enhance rehydration and fluid distribution throughout a
      player's body, so that heat cramps can be completely averted, even during long
      matches in the most challenging environments.

PMID- 12801208
TI  - Blood glucose responses and incidence of hypoglycaemia in elite tennis under
      practice and tournament conditions.
AB  - The purpose of the study was to specify the changes in blood glucose
      concentrations in the course of repeated tournament and practice matches, and to
      quantify the Incidence of hypoglycaemia in elite tennis players. The study
      consisted of two parts. In the first, 147 tournament players completed a
      questionnaire about the incidence of hypoglycaemic symptoms during repeated
      tennis matches. In the second part of the study, the players participated in two
      subsequent matches (one singles match followed by a doubles) under (T) tournament
      (n = 57) and (P) practice (n = 20) conditions. Of the 147 players consulted, 94
      (63.9%) reported experiences with hypoglycaemic symptoms during a tennis
      tournament (n = 80) and/or tennis practice (n = 62). The warm-up period for the
      second match day was identified as the most sensitive point for the occurrence of
      hypoglycaemic symptoms (n = 29), compared to the final stages of the first (n =
      11) or second match (n = 7). Under both practice and tournament conditions, a
      significant (p < 0.01) drop in blood glucose concentration was found during the
      warm-up period for the second match per day (T: from 5.8 +/- 1.4 mmol x L(-1) to
      4.3 +/- 0.8 mmol x L(-1) and P: from 5.4 +/- 1.1 mmol x L(-1) to 4.1 +/- 1.5 mmol
      x L(-1)). In conclusion, precautions should be taken to prevent a sudden drop in
      blood glucose concentration and hypoglycaemic symptoms during the early stages of
      a player's second tennis match in one day.

PMID- 12801209
TI  - A practical method of estimating energy expenditure during tennis play.
AB  - This study aimed to develop a practical method of estimating energy expenditure
      (EE) during tennis. Twenty-four elite female tennis players first completed a
      tennis-specific graded test in which five different Intensity levels were applied
      randomly. Each intensity level was intended to simulate a "game" of singles
      tennis and comprised six 14 s periods of activity alternated with 20 s of active
      rest. Oxygen consumption (VO2) and heart rate (HR) were measured continuously and
      each player's rate of perceived exertion (RPE) was recorded at the end of each
      intensity level. Rate of energy expenditure (EE(VO2)) during the test was
      calculated using the sum of VO2 during play and the 'O2 debt' during recovery,
      divided by the duration of the activity. There were significant individual linear
      relationships between EE(VO2) and RPE, EE(VO2) and HR (r > or = 0.89 & r > or =
      0.93; p < 0.05). On a second occasion, six players completed a 60-min singles
      tennis match during which VO2, HR and RPE were recorded; EE(VO2) was compared
      with EE predicted from the previously derived RPE and HR regression equations.
      Analysis found that EE(VO2) was overestimated by EE(RPE) (92 +/- 76 kJ x h(-1))
      and EE(HR) (435 +/- 678 kJ x h(-1)), but the error of estimation for EE(RPE) (t =
      -3.01; p = 0.03) was less than 5% whereas for EE(HR) such error was 20.7%. The
      results of the study show that RPE can be used to estimate the energetic cost of
      playing tennis.

PMID- 12801210
TI  - Range of motion in junior tennis players participating in an injury risk
      modification program.
AB  - This study evaluated changes in range of motion (ROM) in competitive male and
      female junior tennis players participating in a specific conditioning program
      over a two-year period. Subjects were also compared to an age and sex-matched
      control group of players not performing the exercises. Fifty-one tennis players,
      29 male (mean age 13.6) and 22 female (mean age 13.2) entered the study. Baseline
      ROM measurements were performed on all players upon entering the study. The
      conditioning program employed standardised stretch-hold-relax flexibility
      exercises for all the areas tested. These exercises were taught to the players
      and each athlete was given a video of the exercises. Compliance with the program
      was assessed by exercise logs, the parents, and the athletes. High compliers were
      compared to low compliers. Mean changes in the combined ROM measurements over
      time indicate improvement in flexibility in most anatomical areas after one year
      of participation, with small improvements in the second year. With the exception
      of forearm supination, there were no differences between high compliers and low
      compliers. Compared to controls, the experimental group showed significant
      improvement in sit and reach, dominant and nondominant shoulder internal
      rotation, dominant and nondominant shoulder external rotation, nondominant
      gastrocnemius, dominant iliotibial band, dominant and nondominant hip internal
      rotation, dominant and nondominant hip external rotation, dominant and
      nondominant forearm pronation, and dominant wrist flexion. The areas of greatest
      significant change were in the shoulder and back, which correspond to the areas
      of most clinical risk of Injury. In conclusion, joint ROM can be positively
      influenced with a specific conditioning program.

PMID- 12801211
TI  - Age specific isokinetic glenohumeral internal and external rotation strength in
      elite junior tennis players.
AB  - The high incidence of overuse shoulder injuries in elite junior tennis players is
      often attributed to both the high repetitive stresses inherent in the game, as
      well as muscular imbalances in the humeral rotators. The purpose of this study
      was to isokinetically measure concentric glenohumeral joint internal and external
      rotation strength, to develop a bilateral descriptive profile in elite junior
      tennis players across two age ranges. One hundred forty seven elite junior
      players between the ages of 12 and 21 were bilaterally tested on a Cybex
      isokinetic dynamometer with 90 degrees of abduction. Players were analysed in two
      groups (12-17 and 18-21 years of age), using isokinetic variables of peak torque
      and work relative to body weight. Data analysis consisted of ANOVAs, with
      dependent t-tests used for post-hoc testing where main effect differences were
      identified. Results indicated no significant main effect difference in the
      isokinetic relative parameters between the two age groups (p > .01).
      Significantly greater (p < .001) dominant arm internal rotation was measured in
      both groups for both males and females, with no significant difference in
      external rotation strength measured between extremities in either age group.
      These data show specific adaptations in shoulder strength and identify a relative
      muscular imbalance between the internal and external rotators on the dominant arm
      of elite junior tennis players. Normative data presented in this study can assist
      clinicians and researchers in interpreting isokinetic test results in elite
      junior tennis players.

PMID- 12801212
TI  - Hip and shoulder internal rotation range of motion deficits in professional
      tennis players.
AB  - One hundred tennis players were recruited from the professional men's tennis tour
      to investigate the correlation between hip internal rotation deficits and low
      back pain (LBP), as well as shoulder internal rotation deficits and shoulder
      pain. A statistically significant correlation was observed between dominant
      shoulder internal rotation deficits and shoulder pain. Also observed was a
      statistically significant correlation between lead hip internal rotation deficits
      and lumbar extension deficits with LBP. We conclude that due to repetitive
      demands on the dominant shoulder and repetitive pivoting at the lead hip, the
      cycle of microtrauma and scar formation leads to capsular contracture and
      subsequent reduction in internal range of motion. It is likely that the
      limitation in lumbar extension in the symptomatic group is not only due to
      decreased flexibility from an increased load on the spine, but also due to a
      protective mechanism to prevent further exacerbation of the LBP. Physical
      conditioning that includes shoulder as well as hip internal rotation stretching
      programs should therefore be essential aspects in the treatment of tennis players
      with shoulder pain and LBP respectively.

PMID- 12801213
TI  - Technique effects on upper limb loading in the tennis serve.
AB  - The purpose of this study was to compare the shoulder and elbow joint loads
      during the tennis serve. Two synchronised 200 Hz video cameras were used to
      record the service action of 20 male and female players at the Sydney 2000
      Olympics. The displacement histories of 20 selected landmarks, were calculated
      using the direct linear transformation approach. Ball speed was recorded from the
      stadium radar gun. The Peak Motus system was used to smooth displacements, while
      a customised inverse-dynamics program was used to calculate 3D shoulder and elbow
      joint kinematics and kinetics. Male players, who recorded significantly higher
      service speeds (male = 183 km hr(-1): female = 149 km hr(-1)) recorded
      significantly higher normalised and absolute internal rotation shoulder torque at
      the position when the arm was maximally externally rotated (MER) (male = 4.6% and
      64.9 Nm: female = 3.5% and 37.5 Nm). A higher absolute elbow varus torque (67.6
      Nm) was also recorded at MER, when compared with the female players (41.3 Nm).
      Peak normalised horizontal adduction torque (male = 7.6%: female = 6.5%),
      normalised shoulder compressive force (male = 79.6%: female = 59.1%) and absolute
      compressive force (male = 608.3 N: female = 363.7 N), were higher for the male
      players. Players who flexed at the front knee by 7.6 degrees, in the backswing
      phase of the serve, recorded a similar speed (162 km hr(-1)), and an increased
      normalised internal rotation torque at MER (5.0%), when compared with those who
      flexed by 14.7 degrees. They also recorded a larger normalised varus torque at
      MER (5.3% v 3.9%) and peak value (6.3% v 5.2%). Players who recorded a larger
      knee flexion also recorded less normalised and absolute (4.3%, 55.6 Nm) peak
      internal rotation torque compared with those with less flexion (5.6%, 63.9 Nm).
      Those players who used an abbreviated backswing were able to serve with a similar
      speed and recorded similar kinetic values. Loading on the shoulder and elbow
      joints is higher for the male than female players, which is a reason for the
      significantly higher service speed by the males. The higher kinetic measures for
      the group with the lower knee flexion means that all players should be encouraged
      to flex their knees during the backswing phase of the service action. The type of
      backswing was shown to have minimal influence on service velocity or loading of
      the shoulder and elbow joints.

PMID- 12801214
TI  - Kinetics of the upper extremity in the open and square stance tennis forehand.
AB  - Seven right-handed teaching professionals and eight intermediate tennis players
      were filmed using two high-speed cameras (100 Hz) as they performed open and
      square stance forehand drives. Three-dimensional coordinates (3D) were
      reconstructed using the DLT method. A three-segment rigid body model of the
      racket and upper extremity was used to calculate the kinetics of the wrist,
      elbow, and shoulder joints up to impact. The open stance created lower resultant
      velocities of the racket at impact (21.2 and 15.8 m/s) than the square stance
      (22.3 and 16.4 m/s) for professional and intermediate subjects, respectively. The
      largest components of the resultant joint torques were generated by the shoulder
      horizontal adductors, followed by elbow varus torques, and shoulder internal
      rotation torques. Torques were similar across stance and skill level except for
      significantly (p < 0.05) greater peak shoulder internal rotation torques in the
      square compared to the open stance, greater peak wrist flexion torques in the
      intermediate compared to the professionals, and greater peak wrist flexion
      torques in the square stance compared to the open stance. The data did not
      support the hypothesis that the open stance technique creates greater loading
      throughout the upper extremity than the square stance technique. Peak upper
      extremity torques were similar to peak torques reported for baseball pitching and
      represent loads that could contribute to strength imbalances and overuse
      injuries.

PMID- 12801215
TI  - Effect of ball size on player reaction and racket acceleration during the tennis
      volley.
AB  - The purpose of this study was to examine the effect of ball size on reaction time
      (from ball projection to initial racket movement), movement time (from ball
      projection to ball-racket impact), mean rectified acceleration and vibration
      frequency of the racket during the impact phase (100 ms duration after ball
      racket impact) of the tennis volley. Twenty-nine beginning to intermediate level
      tennis players performed volleys under 18 experimental conditions including
      variations in lateral contact location (forehand and backhand), ball type (Penn
      oversize, Wilson oversize, regular size), and ball speed (fast, medium, slow). A
      ball machine was shielded so that the subjects could not predict the ball
      trajectory before it was released from the machine. Outcome measures were
      determined using a miniature uni-axial accelerometer and a Photogate timing
      device. ANOVA with repeated measures and Tukey's post hoc tests were used in
      statistical analyses (p < .025). The reaction times for the fast speed were
      significantly shorter than the corresponding times for the slow speed and the
      reaction times for the forehand volley were significantly shorter than that of
      the backhand volley. The significant interaction in movement time between ball
      speed and ball type indicates that the benefits of the larger ball (to slow the
      game down) increase as the ball speed increases. No significant effect of ball
      type or ball speed, or interactions were found on mean rectified acceleration and
      vibration frequency. These results suggest that oversized balls would not cause
      an increased load to the hitting arm while executing a tennis volley.

PMID- 12801216
TI  - Bounce of a tennis ball.
AB  - The bouncing of a tennis ball on a tennis court surface is analysed by making
      several simplifying assumptions about the physics of the interaction. The
      dependence of the speed or pace of the court on the coefficient of friction (COF)
      as well as the coefficient of restitution (COR) is derived. The mathematics of a
      court's speed is investigated to see how much slow courts tend to reduce the
      speed of the game. It is found that players must increase their racket head speed
      by 25% if they wish to compensate for the extra loss of ball speed on slow
      courts.

PMID- 12801217
TI  - Player sensitivity to changes in string tension in a tennis racket.
AB  - Forty-one advanced recreational tennis players were tested to determine their
      ability to detect differences in string tension in a tennis racket. Subjects were
      given pairs of rackets that varied in tension by up to 98 N (10 kg) and were
      asked whether they noticed a difference in tension and if so, which racket was
      strung at a higher tension. Only 11 (27%) of those tested could correctly
      identify a tension difference of 5 kg (11 lb) or less. Fifteen (37%) could not
      pick a difference of 10 kg (22 lb). To examine the importance of sound as a means
      of discrimination, an additional test was undertaken where participants wore
      earplugs. Of the 26 subjects undertaking this additional test, only 6 (23%) were
      successful. It was concluded that advanced recreational tennis players
      demonstrated limited ability to correctly identify differences in string tension
      and that impact sound was an important factor for those participants who were
      successful at various levels of discrimination.

PMID- 12801218
TI  - 2003 Claude S. Hudson Award address in carbohydrate chemistry. Heparin: structure
      and activity.

PMID- 12801219
TI  - Deoxyribonucleoside 2'- or 3'-mixed disulfides: prodrugs to target ribonucleotide
      reductase and/or to inhibit HIV reverse transcription.
AB  - Herein, we report the design, synthesis, and biological effects of nucleosides
      bearing a disulfide function on the sugar ring as prodrugs of potentially active
      mercaptonucleotides that can target ribonucleotide reductase or reverse
      transcriptase. We show that cytidine derivatives efficiently reduce dNTP pools in
      human CEM/SS cells and that 3'-deoxythymidin-3'-yl methyl disulfide is able to
      interfere with both cellular dNTP synthesis and HIV reverse transcription.

PMID- 12801221
TI  - QSAR and proteo-chemometric analysis of the interaction of a series of organic
      compounds with melanocortin receptor subtypes.
AB  - We have created quantitative structure-activity relationship (QSAR) models
      describing the interaction of a series of 54 organic compounds with four
      melanocortin (MC) receptor subtypes, MC(1), MC(3), MC(4), and MC(5). In addition
      to traditional QSAR analysis, we applied our recently developed proteo
      chemometrics approach. Proteo-chemometrics is based on the combined analysis of
      series of receptors and ligands, wherein descriptions of ligands, proteins, and
      so-called ligand-protein cross-terms are correlated with interaction activities.
      The compounds were characterized by structural descriptors, including three
      dimensional grid-independent descriptors (GRINDs), topological descriptors, and
      geometrical descriptors. Description of receptors was obtained by computing the
      receptors' amino acid sequence identities. Both the QSAR and proteo-chemometrics
      approaches resulted in models with essentially the same statistical significance:
      the cross-validated correlation coefficient q(2) for the proteo-chemometric model
      being 0.71, while for the QSAR models the q(2)s were 0.75, 0.68, 0.63, and 0.71
      for the MC(1), MC(3)(-)(5) receptor, respectively. However, the proteo
      chemometrics modeling provided more detailed information about receptor-ligand
      interactions and determinants for receptor subtype selectivity than did QSAR.

PMID- 12801220
TI  - Spirocyclopropyl beta-lactams as mechanism-based inhibitors of serine beta
      lactamases. Synthesis by rhodium-catalyzed cyclopropanation of 6
      diazopenicillanate sulfone.
AB  - Class A-class C mechanism-based beta-lactamase inhibitors were designed on the
      basis of the intermediacy of an oxycarbenium species capable of cross-linking
      with amino acids residues in the active site. Penams 24 and 27 were very potent
      against AmpC in vitro. The MIC values of 24 in combination with piperacillin
      against class A and class C producing organisms showed improvement over
      clinically used tazobactam.

PMID- 12801222
TI  - Inhibition of Cdc25 phosphatases by indolyldihydroxyquinones.
AB  - Overexpression of the Cdc25A and Cdc25B dual-specificity phosphatases correlates
      with a wide variety of cancers, making the Cdc25s attractive drug targets for
      anticancer therapies. However, the search for good lead molecules has been
      hampered by the reactivity of the active site thiolate anion and the flat solvent
      exposed active site region. We describe here the indolyldihydroxyquinones, a new
      class of inhibitors of Cdc25 that bind reversibly to the active site with
      submicromolar potency. Structure-activity relationships in the 50 derivatives of
      the lead molecule 2,5-dihydroxy-3-(1H-indol-3-yl)[1,4]benzoquinone show
      interesting and consistent trends identifying features required for inhibition of
      all three isoforms of Cdc25. The compounds do not show time-dependent inhibition,
      indicating that they form neither covalent adducts with nor oxidize the active
      site thiol. Our best compounds, 2,5-dihydroxy-3-(7-farnesyl-1H-indol-3
      yl)[1,4]benzoquinone and 2,5-dihydroxy-3-(4,6-dichloro-7-farnesyl-1H-indol-3
      yl)[1,4]benzoquinone, are competitive with substrate for the active site and
      yield K(i)s of 640 and 470 nM, respectively. Binding of the
      indolylhydroxyquinones is diminished by three, but not by six other, specific
      mutations in the active site region. Additionally, the flexible C-terminal tail
      required for binding of protein substrate is also required for binding
      derivatives with hydrophobic modifications at the 7-position. The
      indolyldihydroxyquinones compete effectively with the protein substrate for Cdc25
      in vitro and lead to rapid cell death in vivo. Thus, the indolyldihydroxyquinones
      will serve as useful lead molecules for drug discovery and further cell-based
      studies on the role of Cdc25s in cell cycle control.

PMID- 12801223
TI  - Dual probes for the dopamine transporter and sigma1 receptors: novel piperazinyl
      alkyl-bis(4'-fluorophenyl)amine analogues as potential cocaine-abuse therapeutic
      agents.
AB  - Both dopamine uptake inhibitors and sigma(1) receptor antagonists have been
      implicated as potential pharmacotherapeutics for the treatment of cocaine abuse.
      While the dopamine uptake inhibitors may share with cocaine neurochemical
      mechanisms underlying reinforcing properties, sigma(1) antagonists have been
      shown to attenuate some behavioral actions and toxic side effects associated with
      cocaine overdose. Rimcazole, a sigma(1) receptor antagonist that binds to the DAT
      (K(i) = 224 nM), is not behaviorally cocaine-like and attenuates some of the
      behavioral actions of cocaine. To determine the roles of both DAT and sigma(1)
      receptors in the behavioral actions of rimcazole, a series of analogues was
      synthesized. Initial studies identified two analogues (1 and 4) that showed high
      to moderate affinities for both DAT and sigma(1) receptors and failed to show
      cocaine-like discriminative stimulus (DS) effects. A second series of bis(4'
      fluorophenyl)amine analogues have now been prepared in which the most potent DAT
      compound, 19 (K(i) = 8.5 nM), was selective over serotonin transporter (SERT/DAT
      = 94), norepinephrine transporter (NET/DAT = 63), and sigma(1) receptor binding
      (sigma(1)/DAT = 44). In addition, two other analogues 10 and 17 showed superior
      selectivity for DAT over SERT (170- and 140-fold, respectively) and DAT over NET
      (219- and 190-fold, respectively) but were essentially equipotent at DAT and
      sigma(1) receptors (10; K(i) = 77 and 124 nM, respectively, 17; K(i) = 28 and 13
      nM, respectively). CoMFA studies at both DAT and sigma(1) receptors were
      performed to examine structural requirements for optimal binding at these two
      targets as well as to assess differences between them. Behavioral evaluation of
      analogues with varying affinities for both DAT and sigma(1) receptors may provide
      a novel approach toward designing medications for cocaine abuse.

PMID- 12801224
TI  - Characterization of a series of 3-amino-2-phenylpropene derivatives as novel
      bovine chromaffin vesicular monoamine transporter inhibitors.
AB  - A series of 3-amino-2-phenylpropene (APP) derivatives have been synthesized and
      characterized as novel competitive inhibitors, with K(i) values in the microM
      range, for the bovine chromaffin granule membrane monoamine transporter(s)
      (bVMAT). Although, these inhibitors are structurally similar to the bVMAT
      substrate tyramine, none of them were measurably transported into the granule.
      Structure-activity studies have revealed that, while the 3'- or 4'-OH groups on
      the aromatic ring enhance the inhibition potency, Me or OMe groups in these
      positions reduce the inhibition potency. Halogen substitution on the 4'-position
      of the aromatic ring causes gradual increase of the inhibition potency parallel
      to the electron donor ability of the halogen. Substituents on the NH(2) as well
      as on the 3-position of the alkyl chain reduce the inhibition potency.
      Comparative structure-activity analyses of APP derivatives with tyramine and the
      neurotoxin 1-methyl-4-phenylpyridinium suggest that the flexibility of the side
      chain and the relative orientation of the NH(2) group may be critical for the
      efficient transport of the substrate through the bVMAT. Comparable bVMAT
      affinities of these inhibitors to that of DA and other pharmacologically active
      amines suggest that they are suitable for the structure-activity and mechanistic
      studies of monoamine transporters and may also be useful in modeling the
      mechanism of action of amphetamine-related derivatives.

PMID- 12801225
TI  - Synthesis and characterization of the first fluorescent antagonists for human 5
      HT4 receptors.
AB  - Fluorescent antagonists for human 5-HT(4) receptors were synthesized based on
      ML10302 1, a potent 5-HT(4) receptor agonist and on piperazine analogue 2. These
      molecules were derived with three fluorescent moieties, dansyl, naphthalimide,
      and NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl), through alkyl chains. The
      synthesized molecules were evaluated in binding assays on the recently cloned
      human 5-HT(4(e)) receptor isoform stably expressed in C6 glial cells with
      [(3)H]GR113808 as the radioligand. The affinity values depended upon the basal
      structure together with the alkyl chain length. The derivatives based on ML10302
      were more potent ligands than the derivatives based on piperazine analogue. For
      ML10302-based ligands, dansyl and NBD derivatives attached through a chain length
      of one carbon atom 17a and 32, respectively, led to affinities close to the
      affinity of ML10302. The most potent compounds 17a, 28, and 32 produced an
      inhibition of the 5-HT stimulated cyclic AMP synthesis in the same cellular
      system with nanomolar K(b) values. Fluorescent properties of 17a, 28, and 32 were
      more particularly studied. Interactions of the fluorescent ligand 28 with the h5
      HT(4(e)) receptor were indicated using h5-HT(4(e)) receptor transfected C6 glial
      cell membranes and entire cells. Ligand 28 was also used in fluorescence
      microscopy experiments in order to label h5-HT(4(e)) receptor transfected C6
      glial cells, and subcellular localization of these receptors was more precisely
      determined using confocal microscopy.

PMID- 12801226
TI  - Utilization of a beta-aminophosphotyrosyl mimetic in the design and synthesis of
      macrocyclic Grb2 SH2 domain-binding peptides.
AB  - Grb2 SH2 domains are protein-docking modules that exert important functions in
      both normal and pathogenic signal transduction processes. Development of
      synthetic Grb2 SH2 domain binding ligands is being pursued by several groups as
      potential new therapies for a variety of diseases, including certain cancers. In
      these efforts, macrocyclization has been successfully utilized to take advantage
      of preferential recognition by Grb2 SH2 domains of ligands in beta-bend
      conformations. Recent examples of this approach include olefin-metathesis-derived
      macrocycles that employ ring closure at the beta-position of key pTyr-mimicking
      residues. In the current study, a novel phosphatase-stable beta-amino-pTyr
      mimetic designated "Pmp(beta)" was utilized to prepare variants of previously
      reported olefin-metathesis-derived macrocycles. An initial set of simplified
      cyclic peptides lacking key naphthyl side chain functionality was first
      synthesized to determine optimum ring size, with results indicating that a four
      unit ring-closing segment was appropriate. On the basis of these findings,
      macrolactamization was undertaken with a more highly functionalized, naphthyl
      containing gamma-amino acid analogue. The resulting cyclic beta-amino peptide is
      the first of a new class of pTyr-mimetic-containing ligands that may have utility
      in the development of antagonists of both Grb2 SH2 domains and other pTyr
      dependent signaling systems.

PMID- 12801227
TI  - Discovery and structural modification of inhibitors of methionine aminopeptidases
      from Escherichia coli and Saccharomyces cerevisiae.
AB  - A series of pyridine-2-carboxylic acid derivatives were synthesized according to
      the leads from the screening, and potent inhibitors have been obtained by
      structural modification. They have shown submicromolar inhibition of the enzymes
      (for example, for 9n, IC(50) = 130 nM for EcMetAP1 and IC(50) = 380 nM for
      ScMetAP1). They represent small-molecule MetAP inhibitors with novel structures
      different from alkylating fumagillin derivatives and peptidic bestatin-based
      MetAP inhibitor.

PMID- 12801228
TI  - The most potent organophosphorus inhibitors of leucine aminopeptidase. Structure
      based design, chemistry, and activity.
AB  - A new class of very potent inhibitors of cytosol leucine aminopeptidase (LAP), a
      member of the metalloprotease family, is described. The X-ray structure of bovine
      lens leucine aminopeptidase complexed with the phosphonic acid analogue of
      leucine (LeuP) was used for structure-based design of novel LAP inhibitors and
      for the analysis of their interactions with the enzyme binding site. The
      inhibitors were designed by modification of phosphonic group in the LeuP
      structure toward finding the substituents bound at the S' side of the enzyme.
      This resulted in two classes of compounds, the phosphonamidate and phosphinate
      dipeptide analogues, which were synthesized and evaluated as inhibitors of the
      enzyme. The in vitro kinetic studies for the phosphinate dipeptide analogues
      revealed that these compounds belong to the group of the most effective LAP
      inhibitors found so far. Their further modification at the P1 position resulted
      in more active inhibitors, hPheP[CH(2)]Phe and hPheP[CH(2)]Tyr (K(i) values 66 nM
      and 67 nM, respectively, for the mixture of four diastereomers). The binding
      affinities of these inhibitors toward the enzyme are the highest, if considering
      all compounds containing a phosphorus atom that mimic the transition state of the
      reaction catalyzed by LAP. To evaluate selectivity of the designed LAP
      inhibitors, additional tests toward aminopeptidase N (APN) were performed. The
      key feature, which determines their selectivity, is structure at the P1'
      position. Aromatic and aliphatic substituents placed at this position strongly
      interact with the LAP S1' binding pocket, while a significant increase in binding
      affinity toward APN was observed for compounds containing aromatic versus leucine
      side chains at the P1' position. The most selective inhibitor, hPheP[CH(2)]Leu,
      binds to LAP with 15 times higher affinity than to APN. One of the studied
      compounds, hPheP[CH(2)]Tyr, appeared to be very potent inhibitor of APN (K(i) =
      36 nM for the mixture of four diastereomers). The most promising LAP inhibitors
      designed by computer-aided approach, the phosphonamidate dipeptide analogues,
      were unstable at pH below 12, because of the P-N bond decomposition, which
      excluded the possibility of determination of their binding affinities toward LAP.

PMID- 12801229
TI  - Discovery of a potent and selective protein kinase CK2 inhibitor by high
      throughput docking.
AB  - To assess the potential of protein kinase CK2 as a target for developing new
      antitumor agents, we have undertaken a search for inhibitors of this enzyme. As
      part of this effort, we report here the discovery of the potent and selective CK2
      inhibitor (5-oxo-5,6-dihydroindolo[1,2-a]quinazolin-7-yl)acetic acid. We
      identified this inhibitor of a novel structural type by high-throughput docking
      of our corporate compound collection in the ATP binding site of a homology model
      of human CK2, using an appropriate protocol. The synthesis of the inhibitor as
      well as that of related analogues whose CK2 inhibitory activities give support to
      the binding mode proposed by the docking program is described. The results
      obtained suggest that virtual screening of a 3D database by molecular docking is
      a useful approach for lead finding provided that adapted postdocking filtering
      and reranking procedures are applied to the primary hit list.

PMID- 12801230
TI  - Synthesis and biological evaluation of N1-(anthracen-9-ylmethyl)triamines as
      molecular recognition elements for the polyamine transporter.
AB  - An efficient modular synthesis of N(1)-substituted triamines containing different
      tether lengths between nitrogen centers was developed. A series of N(1)-(9
      anthracenylmethyl)triamines were evaluated for biological activity in L1210
      (murine leukemia), alpha-difluoromethylornithine (DFMO)-treated L1210, Chinese
      hamster ovary (CHO), and CHO-MG cell lines. All triamines 8 had increased potency
      in DFMO-treated L1210 cells. The 4,4- and 5,4-triamine systems had the highest
      affinity for the polyamine transporter (PAT) with L1210 K(i) values of 1.8 and
      1.7 microM, respectively. This trend was also reflected in the CHO studies.
      Surprisingly, the respective 4,4- and 5,4-triamine systems had 150-fold and 38
      fold higher cytotoxicity in CHO cells containing active polyamine transporters.
      Initial microscopy studies revealed the rapid formation of vesicular structures
      within A375 melanoma cells treated with the N(1)-(9
      anthracenylmethyl)homospermidine (4,4-triamine) conjugate. In summary, the 4,4-
      and 5,4-triamines were identified as selective vector motifs to ferry anthracene
      into cells via the PAT.

PMID- 12801231
TI  - Molecular requirements for targeting the polyamine transport system. Synthesis
      and biological evaluation of polyamine-anthracene conjugates.
AB  - A series of nine N(1)-(9-anthracenylmethyl)tetraamines (e.g., Ant-4,4,4
      tetraamine) were synthesized and evaluated for cytotoxicity in L1210, alpha
      difluoromethylornithine (DFMO)-treated L1210, Chinese hamster ovary (CHO), and
      CHO-MG cell lines. Surprisingly, the 3,3,4- and 3,4,3-tetraamine motifs had the
      same or decreased cytotoxicity in DFMO-treated L1210 cells, whereas the rest of
      the tetraamine systems were usually more cytotoxic and gave lower IC(50) values
      in this treated cell line. The most sensitive derivatives to DFMO treatment were
      the Ant-4,4,3- and Ant-4,4,4-tetraamine analogues, which were 7 and 5 times more
      cytotoxic in DFMO-treated L1210 cells, respectively. K(i) values for each of the
      anthracenylmethyl(Ant)-polyamine conjugates were determined in L1210 cells and
      revealed that these systems are high-affinity ligands for the polyamine
      transporter (PAT). Mixed results were observed in the CHO and CHO-MG assays. The
      4,4,4- and 5,4,4-tetraamine motifs were 3 times more toxic to CHO cells with
      active polyamine transporters. For example, the Ant-4,4,4-tetraamine conjugate
      displayed IC(50) values of 11 microM in CHO cells and 33 microM in CHO-MG cells,
      a PAT-deficient cell line. This suggested that these derivatives used the PAT in
      part to access cells. However, most of the other tetraamine derivatives had
      similar potencies in both the CHO and CHO-MG cell lines. In terms of vector
      design, higher affinity for the PAT (lower K(i) values) did not translate into
      higher potency for the tetraamine conjugate. In contrast, the related triamine
      systems, which had micromolar K(i) values in L1210 cells, were more efficacious
      and selective. In one case, the 4,4-triamine motif imparted 150-fold higher
      potency in CHO cells than the CHO-MG mutant. A deconvolution microscopy study in
      A375 melanoma cells revealed a rapid internalization of the Ant-4,4-triamine as
      fluorescent vesicles, whereas the Ant-4,4,4-tetraamine remained mostly at the
      cell surface. These findings help define the key characteristics required for
      selective delivery of polyamine-drug conjugates into cell types with active
      polyamine transporters.

PMID- 12801232
TI  - Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid
      retinoid X receptor modulators are active in models of type 2 diabetes.
AB  - Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin
      sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM).
      Unfortunately, they also produce dramatic increases in triglycerides and profound
      suppression of the thyroid hormone axis. Here we describe the design and
      synthesis of new RXR modulators that retain the insulin-sensitizing activity of
      RXR agonists but produce substantially reduced side effects. These molecules bind
      selectively and with high affinity to RXR and, unlike RXR agonists, do not
      activate RXR homodimers. To further evaluate the antidiabetic activity of these
      RXR modulators, we have designed a concise and systematic structure-activity
      relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid
      scaffold. Selected compounds have been evaluated using insulin-resistant rodents
      (db/db mice) to characterize effects on glucose homeostasis. Our studies
      demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the
      db/db mouse model.

PMID- 12801233
TI  - Synthesis and complement inhibitory activity of B/C/D-ring analogues of the
      fungal metabolite 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'
      trihydroxy- 2',5',5',8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran].
AB  - This paper reports the synthesis and the bioassay of 4-methoxy- and 4
      hydroxyspiro[benzofuran-2(3H)-cyclohexane] partial analogues (5) of the
      complement inhibitory sesquiterpene fungal metabolite 6,7-diformyl
      3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydroxy-2',5',5',8a'
      tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran] (1a, K-76) and its silver
      oxide oxidized product (1b, K-76COOH). The described target compounds represent
      spirobenzofuran B/C/D-ring analogues lacking the A-ring component of the
      prototype structure. The target compounds were evaluated by the inhibition of
      total hemolytic complement activity in human serum. It was observed that the
      structurally simplified analogue 4-methoxyspiro[benzofuran-2(3H)-cyclohexane]-6
      carboxylic acid (5a) exhibited an IC(50) = 0.53 mM similar to the IC(50) = 0.57
      mM that was observed for the natural product derivative 1b. Exhibiting an IC(50)
      = 0.16 mM, the three-ringed partial structure 6-carboxy-7-formyl-4
      methoxyspiro[benzofuran-2(3H)-cyclohexane] (5k)was found to be the most potent
      target compound. Like the natural product, 5k appears to inhibit primarily at the
      C5 activation step and inhibits both the classical and alternative human
      complement pathways. Several other analogues inhibited complement activation in
      vitro at concentrations similar to those required for inhibition by the natural
      product 1b.

PMID- 12801234
TI  - Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3
      pyridyl)acetylerythromycin A derivatives.
AB  - A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were
      synthesized and evaluated. These compounds have significant potent antibacterial
      activity against not only Gram-positive pathogens, including inducibly macrolide
      lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but
      also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate
      acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin,
      whereas it showed only moderate in vivo efficacy in mouse protection tests.
      However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent
      antibacterial activity against almost all of the main causative pathogens of
      community-acquired pneumonia tested, exhibited excellent in vivo efficacy
      comparable to those of second-generation macrolides.

PMID- 12801235
TI  - Synthesis and biological evaluation of 18-methoxycoronaridine congeners.
      Potential antiaddiction agents.
AB  - Variation of the methoxycarbonyl and C-18 substituents of the antiaddictive
      compound 18-methoxycoronaridine, and contraction of its isoquinuclidine ring
      segment, provided 15 congeners for SAR evaluation at opioid and alpha3beta4
      nicotinic acetylcholine receptors. The opioid activities were relatively low, and
      the alpha3beta4 nicotinic acetylcholine receptor activities were found to
      correlate with in vivo antiaddictive activities.

PMID- 12801236
TI  - Synthesis of substituted 6-anilinouracils and their inhibition of DNA polymerase
      IIIC and Gram-positive bacterial growth.
AB  - Certain substituted 6-anilinouracils are potent and selective inhibitors of Gram+
      bacterial DNA polymerase IIIC (pol IIIC). In addition, analogues with 3
      substituents in the uracil ring have potent antibacterial activity against Gram+
      organisms in culture. In an attempt to find optimal anilino substituents for pol
      IIIC binding and optimal 3-substituents for antibacterial activity, we have
      prepared several series of 3-substituted-6-aminouracils and assayed their
      activity against pol IIIC from Bacillus subtilis and a panel of Gram+ and Gram-
      bacteria in culture. The 6-(3-ethyl-4-methylanilino) group and closely related
      substituent patterns maximized pol IIIC inhibition potency. Among a series of 3
      (substituted-butyl)-6-(3-ethyl-4-methylanilino)uracils, basic amino substituents
      increased pol IIIC inhibition, but decreased antibacterial activity. The most
      potent antibacterials were simple hydroxybutyl and methoxybutyl derivatives, and
      hydrophobically substituted piperidinylbutyl derivatives.

PMID- 12801237
TI  - Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as
      amyloid imaging agents.
AB  - The synthesis and evaluation of a series of neutral analogues of thioflavin-T
      (termed BTA's) with high affinities for aggregated amyloid and a wide range of
      lipophilicities are reported. Radiolabeling with high specific activity
      [(11)C]methyl iodide provided derivatives for in vivo evaluation. Brain entry in
      control mice and baboons was high for nearly all of the analogues at early times
      after injection, but the clearance rate of radioactivity from brain tissue varied
      by more than 1 order of magnitude. Upon the basis of its rapid clearance from
      normal mouse and baboon brain tissues, [N-methyl-(11)C]2-(4'-methylaminophenyl)-6
      hydroxybenzothiazole (or [(11)C]6-OH-BTA-1) was selected as the lead compound for
      further evaluation. The radiolabeled metabolites of [(11)C]6-OH-BTA-1 were polar
      and did not enter brain. The binding affinities of [N-methyl-(3)H]6-OH-BTA-1 for
      homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils
      were similar (K(d) = 1.4 nM and 4.7 nM, respectively), but the ligand-to-Abeta
      peptide binding stoichiometry was approximately 400-fold higher for AD brain than
      Abeta(1-40) fibrils. Staining of AD frontal cortex tissue sections with 6-OH-BTA
      1 indicated the selective binding of the compound to amyloid plaques and
      cerebrovascular amyloid. The encouraging in vitro and in vivo properties of
      [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in
      human subject studies of brain Abeta deposition.

PMID- 12801238
TI  - Antiretroviral activity of semisynthetic derivatives of glycopeptide antibiotics.
AB  - A variety of semisynthetic derivatives of natural antibacterial glycopeptide
      antibiotics such as vancomycin, eremomycin, ristocetin A, teicoplanin A(2)-2, DA
      40926, their aglycons, and also the products of their partial degradation with a
      destroyed or modified peptide core show marked anti-retroviral activity in cell
      culture. In particular, aglycon antibiotic derivatives containing various
      substituents of a preferably hydrophobic nature displayed activity against human
      immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine sarcoma virus at
      a 50% inhibitory concentration in the lower micromolar (1-5 microM) concentration
      range while not being cytostatic against human lymphocytic cells at 250 microM or
      higher. The mode of anti-HIV action of the antibiotic aglycon derivatives could
      be ascribed to inhibition of the viral entry process.

PMID- 12801239
TI  - SYNOPSIS: SYNthesize and OPtimize System in Silico.
AB  - We present a de novo design program called SYNOPSIS, that includes a synthesis
      route for each generated molecule. SYNOPSIS designs novel molecules by starting
      from a database of available molecules and simulating organic synthesis steps.
      This way of generating molecules imposes synthetic accessibility on the
      molecules. In addition to a starting database, a fitness function is needed that
      calculates the value of a desired property for an arbitrary molecule. The values
      obtained from this function guide the design process in optimizing the molecules
      toward an optimal value of the calculated property. Two applications are
      described. The first uses an electric dipole moment calculation to generate
      molecules possessing a strong dipole moment. The second makes use of the three
      dimensional structure of a viral enzyme in order to generate high affinity
      ligands. Twenty eight compounds designed with the program resulted in 18
      synthesized and tested compounds, 10 of which showed HIV inhibitory activity in
      vitro.

PMID- 12801240
TI  - 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent,
      selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with
      antihyperglycemic properties.
AB  - Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a
      valuable therapy for type 2 diabetes. The synthesis and structure-activity
      relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2
      cyanopyrrolidines, are described as well as the path that led from clinical
      development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano
      (S)-pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl)
      amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP-LAF237, 12j). The pharmacological
      profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile
      comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results
      suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing
      excellent oral bioavailability and potent antihyperglycemic activity with
      potential for once-a-day administration.

PMID- 12801241
TI  - Conformationally constrained analogues of diacylglycerol. 19. Synthesis and
      protein kinase C binding affinity of diacylglycerol lactones bearing an N
      hydroxylamide side chain.
AB  - The structures of N-hydroxylamides 1a and 1b, previously reported by Lee et al.
      in J. Med. Chem. 2001, 44, 4309-4312 as strong protein kinase C (PK-C) ligands,
      were incorrect and correspond instead to esters 2a and 2b, respectively. Here, we
      report the synthesis and complete characterization of 1a and 1b together with the
      associated biological activity in terms of PK-C binding affinity.

PMID- 12801244
TI  - Advanced nursing practice: what is it?

PMID- 12801243
TI  - Uric acid reduces exercise-induced oxidative stress in healthy adults.
AB  - Uric acid (UA) possesses free-radical-scavenging properties, and systemic
      administration is known to increase serum antioxidant capacity. However, it is
      not known whether this protects against oxidative stress. The effects of raising
      UA concentration were studied during acute aerobic physical exercise in healthy
      subjects, as a model of oxidative stress characterized by increased circulating 8
      iso-prostaglandin F2alpha (8-iso-PGF2alpha) concentrations. Twenty healthy
      subjects were recruited to a randomized double-blind placebo-controlled crossover
      study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1%
      lithium carbonate/4% dextrose vehicle or vehicle alone as control. Subjects
      performed high-intensity aerobic exercise for 20 min to induce oxidative stress.
      Plasma 8-iso-PGF2alpha concentrations were determined at baseline, after exercise
      and after recovery for 20 min. A single bout of high-intensity exercise caused a
      significant increase in plasma 8-iso-PGF2alpha concentrations from 35.0 +/- 4.7
      pg/ml to 45.6 +/- 6.7 pg/ml (P<0.01). UA administration raised serum urate
      concentration from 293 +/- 16 to 487 +/- 16 micromol/l (P<0.001), accompanied by
      increased serum antioxidant capacity from 1786+/-39 to 1899 +/- 45 micromol/l
      (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8
      iso-PGF2alpha concentrations. High UA concentrations are associated with
      increased serum antioxidant capacity and reduced oxidative stress during acute
      physical exercise in healthy subjects. These findings indicate that the
      antioxidant properties of UA are of biological importance in vivo.

PMID- 12801245
TI  - The impact of regular hospitalization of children living with thalassaemia on
      their parents in Sri Lanka: a phenomenological study.
AB  - This paper reports on a small phenomenological study that set out to describe
      what it means to have a child with thalassaemia regularly attending hospital for
      blood transfusion. Ten parents were invited to participate from the thalassaemia
      unit of a large hospital in a north-west province of Sri Lanka. Data were
      collected by in-depth interviews with parents. The participants' experiences are
      described as they reveal, in their own words, what it means to support children
      with this disease. With startling reality, this research portrays the problems
      associated with caring for these children and their regular admission to
      hospital. Three themes are used to present the participant's experience: worries,
      medical services, and helping and being helped. The findings of the study show
      that there have been improvements in the service and treatment of these children
      in Sri Lanka. However, the lives of the parents are still dire. This research
      should be useful locally in terms of increasing awareness of thalassaemia and
      raising the consciousness of Sri Lankan nurses and other health care workers, so
      that they are more aware of the parents' needs. Although phenomenological
      research is not generalizable, it is likely that the experience of the parents in
      this study has similarities throughout the developing world.

PMID- 12801246
TI  - The relationship between the application of the nursing ethical code and nurses'
      work satisfaction.
AB  - Work satisfaction is known to be one of the major factors related to nurses'
      quality of care. Being able to apply the professional principles of training
      influences work satisfaction. The nursing ethical code is a good manifestation of
      these professional principles. The everyday strains on nurses' work might
      compromise the amount of energy invested in following the ethical code. The gap
      between the ethical requirements (as perceived by the nurse) and the perceived
      extent to which they are applied will influence work satisfaction through the
      mediating effect of role conflict. Demographic variables including age, tenure
      and number of children might also exert an effect. Structured questionnaires were
      used to measure the perceptions of nurses regarding their ability to follow the
      ethical code in a large hospital in Israel. Practical considerations meant that
      the questionnaire focused on client privacy issues in the ethical code. Results
      support the mediating hypothesis as the 'ethical gap' did not correlate directly
      with work satisfaction. This paper highlights that professionalization,
      manifested by the ethical code, should be applied on an everyday basis in the
      workplace.

PMID- 12801247
TI  - Fall risk assessment: a prospective investigation of nurses' clinical judgement
      and risk assessment tools in predicting patient falls.
AB  - A prospective cohort study was used to determine the reliability and validity of
      two fall risk assessment tools and nurses' clinical judgement in predicting
      patient falls. The study wards comprised two aged care and rehabilitation wards
      within a 570 bed acute care tertiary teaching hospital in Western Australia.
      Instrument testing included test-retest reliability and calculations of
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy. The test retest reliability of all methods was good. In this
      setting, the three methods of assessing fall risk showed good sensitivity but
      poor specificity. Also, all methods had limited accuracy, and overall, exhibited
      an inability to adequately discriminate between patient populations at risk of
      falling and those not at risk of falling. Consequently, neither nurses' clinical
      judgement nor the fall risk assessment tools could be recommended for assessing
      fall risk in this clinical setting.

PMID- 12801248
TI  - Associations between psychosocial factors and happiness among school adolescents.
AB  - The concept of health contains aspects of social and mental well-being and not
      just the absence of disease. The concept of well-being is sometimes used
      interchangeably with the term happiness, although focus has been on other aspects
      as well. Here we explore associations between happiness and experience of stress
      at school, personal and social factors among 887 Norwegian school adolescents
      participating in a World Health Organization project on health-promoting schools.
      Happiness was measured by a one item question (ordered responses 1-4). The
      psychosocial factors were represented by an average score of 3-12 items. Odds
      ratios of feeling very/quite happy were calculated in multiple logistic
      regression analyses. An increasing degree of stress experience reduced the
      feeling of happiness significantly. Furthermore, increasing levels of general
      self-efficacy increased the odds of feeling happy, whereas the more specific
      measure of school self-efficacy showed no independent effect. Social support from
      teachers also enhanced happiness significantly. A less consistent pattern was
      found for support from peers, but the most happy pupils experienced significantly
      more support than pupils who reported being unhappy. No significant trend was
      found with decision control. We also explored associations between happiness and
      psychosomatic symptoms. Pupils feeling unhappy reported a particular symptom more
      often and they also had the highest mean number of reported symptoms. To evaluate
      whether these health indicators represent different dimensions of health, a
      comparison of strength of associations with common risk factors is made.
      Implications for health promotion practice are discussed.

PMID- 12801249
TI  - Experiences of regional and rural people with cancer being treated with
      radiotherapy in a metropolitan centre.
AB  - This paper explores the issues related to rural people with cancer whose choice
      of radiotherapy treatment necessitated travel and accommodation in a metropolitan
      centre. Semi-structured interviews with 46 participants, from the Toowoomba and
      Darling Downs region of Queensland, Australia, were conducted and the data
      thematically analysed. The specific themes identified were: being away from loved
      ones, maintaining responsibilities whilst undergoing treatment, emotional stress,
      burden on significant others, choice about radiotherapy as a treatment, travel
      and accommodation, and financial burden. This study supports the need for a
      radiotherapy centre in the location of Toowoomba as a way of providing some
      equity and access to such treatment for the rural people of Queensland.

PMID- 12801250
TI  - Operation Safe Haven: the needs of nurses caring for refugees.
AB  - Nurses played a significant role in providing care to Kosovar and East Timorese
      refugees at the East Hills Reception Centre in Sydney, Australia, during
      Operation Safe Haven in 1999-2000. To ascertain the needs of nurses in this
      setting, 13 nurses participated in two focus group interviews, and two in-depth
      interviews were conducted with nursing managers. Qualitative thematic analysis
      was conducted on the resulting transcripts. Nurses reported that, overall, they
      had the necessary clinical skills but needed specific refugee health profiles and
      training in culturally competent and trauma-sensitive care. The nurses
      experienced trauma-related, cultural, environmental and role-related stressors.
      They used a variety of informal psychosocial supports but reported the need for
      ongoing counselling and debriefing. While clinical skills were considered
      important, nurses identified other factors as having more impact on their ability
      to provide comprehensive care for traumatized refugees, particularly their role
      as client advocates.

PMID- 12801251
TI  - The influence of demographic variables and ward type on elderly patients'
      perceptions of needs and satisfaction during acute hospitalization.
AB  - This article reports on a study designed to determine whether demographic
      characteristics of patients such as age, gender and cultural background were
      associated with different perceptions of the importance of and satisfaction with
      various aspects of nursing care. In addition, patients, their family/carer and
      nurses from wards specializing in aged care were compared with general medical
      wards to determine if there were differences in these perceptions. Results
      demonstrated that patients who were older (aged > 80 years), female and from aged
      care wards perceived that physical aspects of nursing care were more important
      than did patients who were younger (aged 65-80 years), male and from medical
      wards. Older patients and those from aged care wards were more satisfied with
      physical care. Nurses need to be aware of these differences and focus on physical
      aspects of care to ensure patient satisfaction better health outcomes.

PMID- 12801252
TI  - A conceptual framework for person-centred practice with older people.
AB  - This paper presents a conceptual framework for person-centred practice with older
      people. The research from which the framework was developed was guided by
      hermeneutic philosophy and integrated processes of conversation analysis and
      reflective conversation in data collection and analysis. The research findings
      suggested that nurses need to be able to particularize the person that the
      patient is, the relationship that exists between them and the patient, and the
      understandings and expectations implicit in the relationship. From these findings
      a conceptual framework for person-centred practice was developed. In the
      framework, person-centredness is premised on the concept of authentic
      consciousness and is operationalized through five imperfect duties. The factors
      that enable person-centredness to operate in practice are identified as the
      patient's values, the nurse's values and the context of the care environment.
      Considerations for implementing the model in practice are highlighted.

PMID- 12801253
TI  - Maintaining oral hydration in older adults: a systematic review.
AB  - Dehydration is the most common fluid and electrolyte imbalance in older adults.
      The objectives were to identify the factors that increase the risk of dehydration
      in older adults, how best to assess the risk and manage oral fluid intake. Data
      sources included Medline, CINAHL, Cochrane Library, Embase and Current Contents,
      which were searched until February 2002. Randomized controlled trials for
      management of adequate fluid intake were undertaken. Cohort and case control
      studies were used for the identification of risk factors for dehydration. Studies
      of assessment tools for the identification of dehydration were also considered.
      Results show that there is no clear determination of the risk factors for
      dehydration and decreased fluid intake. The recommended daily intake of fluids
      should be not less than 1600 mL/24 h in order to ensure adequate hydration. A
      fluid intake sheet and urine specific gravity might be the best methods of
      monitoring daily fluid intake. Regular presentation of fluids to bedridden older
      adults can maintain adequate hydration status. In conclusion, more research is
      required to determine the optimum method of maintaining adequate oral hydration
      in older adults.

PMID- 12801254
TI  - Practical model-based dose-finding in phase I clinical trials: methods based on
      toxicity.
AB  - We describe two practical, outcome-adaptive statistical methods for dose-finding
      in phase I clinical trials. One is the continual reassessment method and the
      other is based on a logistic regression model. Both methods use Bayesian
      probability models as a basis for learning from the accruing data during the
      trial, choosing doses for successive patient cohorts, and selecting a maximum
      tolerable dose (MTD). These methods are illustrated and compared to the
      conventional 3+3 algorithm by application to a particular trial in renal cell
      carcinoma. We also compare their average behavior by computer simulation under
      each of several hypothetical dose-toxicity curves. The comparisons show that the
      Bayesian methods are much more reliable than the conventional algorithm for
      selecting an MTD, and that they have a low risk of treating patients at
      unacceptably toxic doses.

PMID- 12801255
TI  - The contribution of DNA mismatch repair gene defects to the burden of
      gynecological cancer.

PMID- 12801256
TI  - Consolidation treatment of advanced (FIGO stage III) ovarian carcinoma in
      complete surgical remission after induction chemotherapy: a randomized,
      controlled, clinical trial comparing whole abdominal radiotherapy, chemotherapy,
      and no further treatment.
AB  - In a prospective randomized trial, consolidation treatment with radiotherapy or
      chemotherapy was compared with no treatment in a series of 172 patients with
      epithelial ovarian carcinoma, FIGO stage III, with complete surgical remission
      after primary cytoreductive surgery and induction chemotherapy. In the subgroup
      with complete surgical and pathologic remission, progression-free survival was
      significantly (P = 0.032) better in the radiotherapy group (56% at 5 years) than
      in the chemotherapy group (36% at 5 years) and the untreated control group (35%
      at 5 years). Overall survival was also most favorable in the radiotherapy group
      (69% at 5 years). The number of recurrences was lowest in the radiotherapy group.
      In the subgroup with microscopic residual carcinoma there were no significant
      differences in survival between the radiotherapy and the chemotherapy-treated
      patients. Early and late radiation reactions were recorded. Treatment-related
      side effects were seen most frequently in the radiotherapy group. Late intestinal
      radiation reactions of a severe type were recorded in 10%.

PMID- 12801257
TI  - Phase II clinical trial of carboplatin and docetaxel in patients with metastatic
      ovarian cancer: active combination with low incidence of peripheral neuropathy.
AB  - During the past 2 decades there have been chemotherapeutic advances in the
      management of patients with advanced epithelial ovarian cancer. Nevertheless, new
      drug combinations aimed at increasing response and survival and decreasing
      toxicities are under investigation. The aim of this phase II study is to
      determine the feasibility, efficacy and toxicity of docetaxel at a dose of 75
      mg/m2 in combination with Carboplatin at an area under the curve (AUC) of 6, as
      first line treatment in patients with advanced ovarian cancer. 37 patients with
      stage III-IV epithelial ovarian cancer were entered, and are currently evaluable
      for response and toxicity. Treatment was well tolerated. The most common grade
      III and IV toxicities were leukopenia and neutropenia. The incidence of febrile
      neutropenia was 16.2%. Grade II and III sensory peripheral neuropathy occurred in
      8.1% of patients. Peripheral neuropathy resolved in two patients and persisted
      for more than 10 months in one patient. An overall clinical response of 89% was
      documented (95% CI 74.5% to 96.9%). Carboplatin and docetaxel administered
      according to our protocol is an effective alternative to other existing platinum
      taxane based combinations. This treatment is associated with low incidence of
      sensory peripheral neuropathy, which is generally associated with better patient
      compliance and quality of life.

PMID- 12801258
TI  - Can bowel endoscopy predict colorectal surgery in patients with an adnexal mass?
AB  - The objective of this retrospective study was to identify the ability of
      preoperative endoscopy of the lower gastrointestinal tract and other tests to
      predict large bowel resection in patients with an adnexal mass. We reviewed 573
      patients with a suspected adnexal mass admitted for surgery between 1987 and
      1997. Two hundred fifty four patients (44%) had preoperative sigmoidoscopy (n =
      97) or colonoscopy (n = 157). We identified patients who underwent a colorectal
      operation as part of their surgery and correlated surgical findings with the
      results of preoperative endoscopy, preexisting clinical symptoms, preoperative
      pelvic exam and ultrasonography, and the CA125 level. The sensitivity and
      positive predictive value of bowel endoscopy for predicting large bowel surgery
      were 18% and 59%, respectively. Multivariate analysis showed preexisting bowel
      related symptoms, a pelvic exam suggestive of malignancy, a CA125 value >1000
      U/ml, and infiltration of the colorectal wall at bowel endoscopy to be
      independently associated with subsequent colorectal surgery. We conclude that
      preoperative bowel endoscopy cannot accurately predict colon resection in
      patients with a suspected adnexal mass. Preexisting bowel-related symptoms, a
      pelvic exam suggestive of malignancy and a CA125 value >1000 U/ml are associated
      with subsequent colorectal surgery.

PMID- 12801259
TI  - Can we rely on the size of the lymph node in determining nodal metastasis in
      ovarian carcinoma?
AB  - This study endeavored to determine whether lymph node size is a reliable
      indicator in determining lymph node metastasis in common epithelial ovarian
      cancer. We reviewed pathologic sections of pelvic and para-aortic lymph nodes
      removed from 104 ovarian carcinoma patients who underwent either primary surgical
      staging or secondary surgery from January 1994 to July 2001. All sections of each
      individual node were measured in two dimensions. The different sizes of nodes
      were studied statistically to determine the optimal sensitivity and specificity
      in predicting cancer metastasis. A nodal size of 10 mm was a specific point of
      interest. Of 2069 total nodes obtained, 110 nodes (5.3%) had metastatic cancer.
      More than half (55.4%) of these positive nodes had a nodal long axis of 10 mm and
      less. The sensitivity and specificity of nodal size at 10 mm were 44.5% and
      81.1%, respectively. We conclude that lymph node size is not a good indicator in
      determining epithelial ovarian cancer metastasis. Mere sampling of only the
      enlarged nodes does not reflect the true positive incidence of nodal metastasis.
      To avoid inaccurate staging and improper management, complete lymph node
      dissection is proposed as part of surgical staging for ovarian cancer.

PMID- 12801260
TI  - Lack of proliferative activity of surface epithelial inclusion cysts of the
      ovary.
AB  - Surface epithelial inclusion cysts (SEICs) of the ovary are epithelial inclusions
      in the ovarian cortex believed to form from invagination of the surface
      epithelium at the time of ovulation. It has long been theorized that SEICs are
      related to the development of epithelial ovarian cancer. Ki-67 antigen is a
      marker of cell proliferation and has been shown to be prognostic in epithelial
      ovarian cancer. The purpose of this study was to evaluate Ki-67 activity in SEICs
      to evaluate their possible connection to ovarian neoplastic proliferation. A
      retrospective review of benign ovaries removed at the time of pelvic surgery was
      performed. Slides were immunostained with Ki-67. Proliferation index, expressed
      as the percent of cells staining in SEICs, was calculated. Proliferative activity
      was scored as negligible, low, moderate, or high, at <5%, 5-10%, 11-40%, and
      >40%, respectively. Eighteen ovaries from 18 women were evaluated. The percentage
      of Ki-67 positive cells ranged from 0% to 7%. Ki-67 activity in SEICs of the
      ovary is negligible to low. Proliferative activity as assessed by Ki-67 staining
      does not explain any possible relationship of SEICs to epithelial ovarian cancer.

PMID- 12801262
TI  - Does the density of lymphatic vascular space invasion affect the prognosis of
      stage Ib and IIA node negative carcinoma of the cervix?
AB  - Lymphatic vascular space invasion (LVSI) has been noted as a poor prognostic
      factor in many tumors. In some studies of carcinoma of the cervix, LVSI has been
      demonstrated to be independent of other prognostic factors. The aim of this study
      is to evaluate if, by a simple quantitative technique, the density of lymphatic
      invasion could be correlated with the risk of recurrence in node negative early
      stage carcinoma of the cervix. We analyzed the pathology and clinical course of
      71 consecutive patients with stage IB and IIA carcinoma of the cervix treated
      primarily by radical hysterectomy and pelvic lymphadenectomy. All cases had
      negative nodes and adequate surgical margins. There were 67 patients suitable for
      evaluation. Tumour type, grade, stage and the dimensions of the tumor were
      recorded. The density of LVSI was categorized as absent (45%), mild (15%),
      moderate (33%) or severe (7%) depending on the number of lymphatic vascular
      spaces involved per high power field in the worst affected slide. The patients
      were followed for 2-8(1/2) years with a mean follow up of 4 years and 2 months.
      There were 13 recurrences and 7 deaths. All recurrences occurred in less than 2
      years after surgery. The risk of recurrence was 40% for patients with extensive
      LVSI, 32% for moderate, 30% for mild and 3% if LVSI was absent. Only the presence
      of LVSI was associated with an increased risk of recurrence. The density of
      lymphatic invasion as represented by the number of lymphatic spaces occupied on
      the worst histological slide offered no further clinically useful information.

PMID- 12801261
TI  - Cisplatin and vinorelbine as neoadjuvant chemotherapy in locally advanced
      cervical cancer: a phase II study.
AB  - Fifty eight consecutive untreated patients with locally advanced cervical
      carcinoma (LACC) received neoadjuvant chemotherapy (NACT) with cisplatin (CDDP)
      80 mg/sqm (day 1) + vinorelbine (VRL) 25 mg/sqm (day 1 and 8). Three cycles of
      chemotherapy were planned every 21 days. Within 28 days from the completion of
      chemotherapy patients in complete or partial response were submitted to radical
      hysterectomy with pelvic lymphadenectomy. On 155 cycles, hematologic toxicity was
      mild (G3-4 neutropenia and anemia occurred in 16% and 5%, respectively). Forty
      seven patients (81%) were submitted to radical surgery; eight (14%) patients were
      deemed ineligible for surgery because of poor response to treatment, two (3%) for
      anesthesia contraindications and one (2%) refused surgery. At pathologic
      examination 12 patients (25%) had a complete response, one (2%) in-situ
      carcinoma, six (13%) residual microinvasive disease, and 28 (60%) a partial
      response. None had extracervical disease. Eight patients (14%) had microscopic
      lymph node metastases. The number of cycles administered was significantly
      associated with a good pathologic response. Association of CDDP and VRL as NACT
      in LACC appears safe and effective. Low cost and modest toxicity would support
      the initiation of a multicenter randomized phase III trial to compare this
      association with cisplatin alone.

PMID- 12801263
TI  - Morphologic and biologic studies on ten cases of verrucous carcinoma of the vulva
      supporting the theory of a discrete clinico-pathologic entity.
AB  - Ten cases of verrucous carcinoma (VC) of the vulva diagnosed from January 1989 to
      December 1996 were studied. Patient age ranged from 50 to 83 years. The following
      examinations were performed on buffered formalin-fixed material: 1). in situ DNA
      hybridization, probes HPV 6/11, 16/18, 31/35/51; and 2). a series of
      immunohistochemical stainings to demonstrate wild and mutant types of the p53
      protein, cytokeratin expression and pattern distribution (AE1 and AE3), and
      proliferating pattern (MIB 1). In situ DNA hybridization analysis for human
      papillomavirus 6/11, 16/18, 31/35/51 was negative in all cases. Wild and mutant
      types of p53 protein transcribed from related oncosuppressor gene were not
      detected. Keratins AE1 and AE3 showed a peculiar distribution pattern, that is,
      AE1 was uniformly positive in the surface and intermediate layers, while it was
      almost negative in the basal layer which-on the contrary-was mainly positive to
      AE3 keratins. MIB-1 highlighted 10-40% of proliferating cells; however, in all
      cases, 70-80% of MIB-1 positivity was found in the basal layer of the neoplastic
      epithelium. These results seem to show the morphofunctional and growth
      characteristics of neoplastic epithelium, thus stressing that VC should be
      considered as a discrete entity in vulvar tumors.

PMID- 12801264
TI  - Nm23-H1 immunohistochemical expression in multisteps of cervical carcinogenesis.
AB  - To evaluate the expression of nm23-H1 protein in normal, precancerous, and
      cancerous tissues of the uterine cervix and its role in cervical carcinogenesis,
      metastasis and recurrence, 82 cervical specimens, including 30 squamous cell
      carcinomas (SCC), 19 high- and 13 low-grade squamous intraepithelial lesions
      (HSILs and LSILs) and 20 normal samples, were stained using immunohistochemical
      method with streptavidin-biotin peroxidase immunostaining. The Chi-square and
      Fisher's exact tests, as well as Chi-square test for trend, were used for
      comparing nm23-H1 expression among normal, LSIL, HSIL, and cancerous tissues. The
      correlation of nm23 expression with metastasis or recurrence was analyzed using
      Fisher's exact test. There were significant differences in levels of nm23-H1
      expression between LSIL and HSIL (P = 0.016) and between LSIL and SCC (P =
      0.004), but not between HSIL and SCC or normal and LSIL samples. Furthermore, a
      positive relationship was demonstrated for high nm23-H1 protein expression and
      degree of malignant transformation (P < 0.05). Among the 30 SCC cases, high nm23
      H1 expression did not show significant association with either carcinomatous
      metastasis or recurrence (P = 0.123, 0.372, respectively). High nm23-H1
      expression appears related to critical progression of LSIL to HSIL but not to
      metastasis or recurrence of SCC.

PMID- 12801265
TI  - A prognostic insight on in vivo expression of interleukin-6 in uterine cervical
      cancer.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine with a growth promoting role
      in cancers. In an attempt to evaluate the prognostic significance of IL-6, we
      have studied the localization of this cytokine by immunohistochemical methods in
      normal, premalignant, and invasive cervical cancers. We stained frozen sections
      with a monoclonal antibody specific for human IL-6 and demonstrated that tumor
      cells show positivity with high intensity and stromal cells with moderate
      intensity. T cells and macrophages, components of the stroma that secrete IL-6,
      were also looked at. While T cells showed a weak positive correlation, CD68
      positive macrophages showed significant positive correlation (P < 0.05) with IL-6
      positivity in stroma. The patients were followed up for 40 months after treatment
      with standard radiotherapy regimen and showed residual tumor where pretreatment
      IL-6 levels were high. Our results suggest its possible candidature as a
      prognostic indicator of cervical cancer.

PMID- 12801266
TI  - Uterine evacuation with misoprostol during radiotherapy for cervical cancer in
      pregnancy.
AB  - Radiotherapy as definitive treatment for invasive cervical cancer during
      pregnancy causes spontaneous abortion in most cases. Surgical evacuation of the
      uterus is indicated when abortion does not occur, exposing patients to additional
      morbidity. Two Latin American women, diagnosed with FIGO stage IB2 cervical
      cancer at approximately 15 weeks gestation, underwent radiotherapy with
      radiosensitizing chemotherapy. After intrauterine fetal demise was detected, both
      women underwent induction with misoprostol. Results included one complete
      abortion and one incomplete abortion without complications or delays in
      treatment. These cases demonstrate that induction with misoprostol appears to be
      a safe and effective alternative to surgical evacuation of the uterus when
      spontaneous abortion fails to occur during radiotherapy for locally advanced
      cervical cancer.

PMID- 12801267
TI  - Immunohistochemical evaluation of cathepsin D in normal, hyperplastic and
      malignant endometrium: correlation with hormone receptor status c-erbB-2, p53, Rb
      proteins and proliferation associated indices.
AB  - The immunohistochemical expression of cathepsin D was performed in paraffin
      embedded tissue from 79 endometrial carcinomas, 35 cases of hyperplasia, and 32
      normal endometrium using the streptavidin-biotin method to investigate the role
      of cathepsin D (CD) in these lesions and its possible relationship with other
      potential and established prognostic markers. The association between CD and the
      other markers was assessed by univariate analysis. Tumor cell CD expression was
      lower in the group of carcinomas compared to the normal proliferative (P = 0.022)
      and secretory endometrium (P = 0.0005). In addition, hyperplastic cell CD
      expression was lower compared with epithelial cell CD expression in the secretory
      phase of normal endometrium (P = 0.009). Malignant cell CD expression was
      inversely correlated with tumor stromal cells (P = 0.007). A positive
      relationship of stromal cell CD expression with pRb (P = 0.046) and PCNA score (P
      < 0.0001) was detected in the group of carcinomas. In the proliferative phase of
      normal endometrium, epithelial CD expression was positively correlated with
      estrogen status (P = 0.015). The data show that down-regulation of CD expression
      is an early event in endometrial carcinogenesis. In addition, stromal cell CD
      expression may be involved in cell growth process in endometrial carcinomas.

PMID- 12801268
TI  - Cancer history and loss of MSH2 and MLH1 protein expression in patients with
      endometrial hyperplasia.
AB  - In order to evaluate the hereditary background of endometrial hyperplasia
      patients in relation to protein expression of DNA mismatch repair genes, we
      evaluated 69 patients with endometrial hyperplasia and 18 patients with normal
      endometrium having both a personal and family history of cancer (two hereditary
      nonpolypoid colorectal cancer (HNPCC) patients). We obtained personal and family
      histories of cancer for all patients. MSH2 and MLH1 protein expression was
      investigated by immunohistochemical methods. In the endometrial hyperplasia
      patients, 11 had personal histories and 40 had family histories of cancer. Among
      the 11 endometrial hyperplasia patients with a personal history of cancer, most
      cancers were breast or colorectal cancers (82%). In the 40 patients with a family
      history of cancer, colorectal cancer (33%) was the most frequent. The incidence
      of loss of expression of MSH2 and/or MLH1 protein in endometrial hyperplasia
      patients with personal (64%) or family (40%) histories was significantly higher
      than that in patients without such history (no personal: 21% and no family: 10%;
      P = 0.0035 and 0.0065). No protein loss was detected in any of the cases with
      normal endometrium having either a personal or family history of cancer. Our
      results suggest that a portion of endometrial hyperplasia cases having a personal
      or family history of cancer may belong to HNPCC, and that in these cases,
      abnormality of the mismatch repair system may be an early event in endometrial
      carcinogenesis.

PMID- 12801269
TI  - False-negative sentinel node in patients with vulvar cancer: a case study.
AB  - Evidence from recent studies indicates that the technique of sentinel node biopsy
      might be a useful solution for detecting lymph node status for primary vulvar
      cancer without having to perform radical inguinal lymphadenectomy. The patient in
      this report underwent sentinel node biopsy, then bilateral inguino-femoral node
      dissection, and, lastly, radical vulvectomy. The histologic analysis showed a
      well differentiated squamous cell carcinoma with metastases in one right inguinal
      node and one left inguinal node and a false-negative right sentinel node.
      Technically the biopsy of groin sentinel nodes should be quite easy to perform.
      The use of preoperative lymphoscintigraphy and the intraoperative use of the
      gamma probe combined with blue dye helps considerably in identifying lymphatic
      drainage and the sentinel node for vulvar cancer. Further results are needed to
      confirm the value of sentinel node dissection in the treatment of early stage
      vulvar cancer.

PMID- 12801270
TI  - De novo uterine sarcoma with good response to neo-adjuvant chemotherapy.
AB  - We report here the extremely rare case of a 28-year-old woman with advanced stage
      uterine sarcoma arising soon after a cesarean section. She underwent an abdominal
      cesarean section because of a breech presentation. At the time of the procedure,
      there were no abnormal findings such as leiomyoma of the uterus in the abdominal
      cavity. One year later, she was referred to our hospital because of a large
      abdominal tumor. Transabdominal power Doppler ultrasonography and magnetic
      resonance imaging (MRI) showed a large hypervascular tumor in the abdominal
      cavity. Her serum levels, for the two tumor markers carbohydrate antigen CA125
      and LDH, were elevated, at 219 U/ml (< 35 U/ml) and 862 IU/l (115 U/ml-217 U/ml),
      respectively. On the basis of a diagnosis of malignant tumor of gynecological
      origin, exploratory laparotomy was performed, and through biopsy, the tumor was
      found to be advanced undifferentiated uterine sarcoma. She exhibited a good
      response to neoadjuvant chemotherapy consisting of cisplatin, epirubicin, and
      dimethyltriazenoimidazole carboxamide (DTIC) every 28 days, which was
      successfully followed by a hysterectomy.

PMID- 12801271
TI  - Surgical resection of solitary brain metastasis from cervical cancer.
AB  - This is the first report of a patient with cervical cancer who underwent surgical
      resection of a solitary brain metastasis eight years following diagnosis. This
      case is unique because of the indolent nature of the tumor and because the
      patient had resection of metastatic lung nodules three years earlier. In this
      particular case, the patient's survival was not prolonged, so craniotomy and
      resection cannot be recommended in this disease, even when there has been a
      prolonged disease progression-free interval. Palliative management should include
      steroids and radiation therapy.

PMID- 12801272
TI  - Extragenital mullerian adenosarcoma with sarcomatous overgrowth arising in an
      endometriotic cyst in the pouch of Douglas.
AB  - Mullerian adenosarcoma is a neoplasm composed of benign mullerian epithelium and
      a sarcomatous stroma. This tumor classically occurs in the endometrium of
      postmenopausal women and less frequently in the extrauterine genital tract. Rare
      cases of extragenital adenosarcoma have been reported. We present the case of a
      23-year-old female who presented with an extragenital adenosarcoma arising in an
      endometriotic cyst in the pouch of Douglas. The patient was treated with local
      excision, chemotherapy and radiotherapy. At 2 years follow-up she was disease
      free. The literature on extragenital adenosarcoma is reviewed. These tumors are
      clinically more aggressive than their uterine counterparts. Surgical excision is
      the initial treatment modality for these patients. Little information is
      available regarding the efficacy of adjuvant chemotherapy or radiotherapy. This
      is an area that requires further study.

PMID- 12801273
TI  - Extensive pelvic endometriosis with malignant change in tamoxifen-treated
      postmenopausal women.
AB  - The aim of this study was to document a case of tamoxifen-associated extensive
      pelvic endometriosis and attract the attention to this side effect of tamoxifen
      use in the postmenopausal patient. A 74-year-old woman with a history of breast
      carcinoma who received tamoxifen therapy for 2 years was admitted with uterine
      bleeding. Hysteroscopic polypectomy revealed a hyperplastic polyp. Extensive
      pelvic endometriosis was detected at the operation and due to dense adhesions,
      subtotal hysterectomy and bilateral salpingo-oophorectomy were performed. The
      patient continued to use tamoxifen. A supracervical pelvic mass was detected 14
      months later. The cervix, rectum, and the accompanying mass were resected.
      Histopathologic examination revealed endocervical adenocarcinoma and
      endometriosis involving cervix uteri and the rectal muscular wall. The patient
      had two normal cervical smears within the last 3 years and no abnormal appearance
      was detected within the cervical canal in the hysteroscopic examination. As
      cervical cancer occurred in a short period, it might be speculated that tamoxifen
      might have stimulated the proliferative and mitotic activity of cervical
      endometrial tissue which has progressed into invasive cancer in time.

PMID- 12801274
TI  - Langerhans cell histiocytosis of the female genital tract: a literature review.
AB  - Langerhans cell histiocytosis (LCH) is a rare malignant disease involving the
      accumulation of a monoclonal proliferation of cells in various organs, that
      phenotypically resemble Langerhans cells (LC). LCH is not merely a hyperplasia of
      LC, as it typically affects organs that are outside of their normal physiologic
      distribution. Normal Langerhans cells are bone marrow-derived dendritic cells
      that populate the epidermis and are distinguished by the presence of Birbeck
      granules and cell surface protein CD1a. LC act as sentinels; they recognize,
      internalize, and process antigens encountered in the skin. Upon encountering an
      antigen, LC become activated with subsequent maturation and induction of their
      migratory capacity. Langerhans cells in patients with LCH are aberrant and
      profoundly differ from normal LC. The clinical spectrum of LCH is quite diverse;
      multiple organs can be affected. "Pure" genital Langerhans cell histiocytosis is
      a rare presentation, with only 12 previously reported cases. Due to the rarity of
      this disease, treatment of genital LCH is still very diverse. No modality is
      proven to be superior in improving patient outcome, and relapses frequently occur
      after surgery. Dramatic responses of cutaneous and ano-genital lesions to
      thalidomide and interferons have been reported. We advocate the use of immuno
      modulating agents in LCH of the female genital tract first, rather than surgery.

PMID- 12801275
TI  - High dose rate (HDR) cervical ring applicator to control bleeding from cervical
      carcinoma.

PMID- 12801276
TI  - Cervical cancer and laparoscopic staging lymphadenectomy.

PMID- 12801279
TI  - Defining boundaries during joint cavity formation: going out on a limb.
AB  - Whilst factors controlling the site at which joints form within the developing
      limb are recognised, the mechanisms by which articular element separation occurs
      during the formation of the joint cavity have not been determined. Herein, we
      review the relationships between early limb patterning, embryonic movement,
      extracellular matrix composition, local signalling events and the process of
      joint cavity formation. We speculate that a pivotal event in this process
      involves the demarcation of signalling boundaries, established by local mechano
      dependent modifications in glycosaminoglycan synthesis. In our opinion, studies
      that examine early patterning and also focus on local developmental alterations
      in tissue architecture are required in order to help elucidate the fundamental
      principals regulating joint formation.

PMID- 12801280
TI  - The acute phase protein haptoglobin is locally expressed in arthritic and
      oncological tissues.
AB  - Haptoglobin is an acute phase protein known to be highly expressed in the liver.
      Recently, we showed increased local arterial haptoglobin expression after flow
      induced arterial remodelling and found that haptoglobin is involved in cell
      migration and arterial restructuring probably through accumulation of a temporary
      gelatin matrix. Since cell migration and matrix turnover are important features
      in the pathology of arthritis and cancer, we hypothesized that haptoglobin is
      also locally expressed in arthritic and oncological tissues. In this study, we
      investigated local haptoglobin expression in arthritic rats (n = 12) using semi
      quantitative PCR and Western blotting, and we studied haptoglobin mRNA
      localization in human kidney tumours (n = 3) using in situ hybridization. The
      arthritic rats demonstrated an increase of haptoglobin mRNA (2.5-fold, P < 0.001)
      and protein (2.6-fold, P < 0.001) in the arthritic Achilles tendon. Haptoglobin
      protein was also increased in the arthritic ankle (2.6-fold, P < 0.001) but not
      in the non-arthritic knee. In human kidney tumours, tumour and stromal cells
      produced haptoglobin mRNA. This study shows that the liver protein haptoglobin
      is, in addition to the artery, also expressed in arthritic and oncological
      tissues that are recognized for enhanced cell migration and matrix turnover.

PMID- 12801281
TI  - Constitutive nuclear localization and initial cytoplasmic apoptotic activation of
      endogenous caspase-3 evidenced by confocal microscopy.
AB  - The localization of caspases and their substrates in different cellular
      compartments may be one way to regulate apoptosis. Caspase-3-dependent
      proteolysis of inhibitor caspase-activated deoxyribonuclease (ICAD) activates
      caspase-activated deoxyribonuclease (CAD), which induces apoptotic
      internucleosomal DNA degradation. The nuclear localization of ICAD, pro- and
      active-caspase-3 molecules remains a controversial issue. Using a combination of
      immunodetection of endogenous molecules and confocal microscopy, we analysed the
      kinetics of the procaspase-3 and CAD activation induced by FAS triggering in
      Jurkat cells. Through a semi-quantitative image analysis, we showed a
      constitutive nuclear localization of pro-caspase 3 and ICAD in non-apoptotic
      cells. FAS stimulation induced 7A6 apoptotic antigen expression, which could be
      related to three different sequential patterns of nuclear chromatin organization.
      Active-caspase-3 first appeared in the cytoplasm and was next observed in the
      nucleus. Simultaneously, the amount of ICAD located in the nucleus decreased,
      whereas the amount of ICAD located in the cytoplasm remained unchanged. Thus, our
      experiments using in situ immunodetection of endogenous molecules show that the
      ICAD cleavage by the active-caspase-3 probably takes place in the nucleus. These
      results provide new perspectives about the subcellular compartmentation and
      traffic of caspases during the apoptotic process.

PMID- 12801282
TI  - Chronic treatment with the thiazolidinedione, MCC-555, is associated with
      reductions in nitric oxide synthase activity and beta-cell apoptosis in the
      pancreas of the Zucker Diabetic Fatty rat.
AB  - The Zucker Diabetic Fatty (ZDF) rat is a model of impaired insulin sensitivity
      arising from hyperphagia owing to a mutation in the leptin receptor. In time,
      young ZDF rats, which are not initially diabetic, develop impaired pancreatic
      beta-cell function leading to apoptotic cell death. This results in an inability
      to fully compensate for the reduction in insulin sensitivity with hypersecretion
      of insulin. Young, pre-diabetic ZDF rats were treated, over a 4-week period, with
      the thiazolidinedione compound MCC-555, and the islet morphology studied in
      comparison to ZDF rats not given MCC-555. In particular, changes in the apoptotic
      incidence, as measured using TUNEL staining to localize apoptotic cells, were
      studied over the 4-week period. Changes in the induction of nitric oxide synthase
      and in the accumulation of nitrate/nitrite within the pancreas were also studied
      during the time course of administration of MCC-555. The study has demonstrated
      that the administration of MCC-555 significantly decreases the apoptotic
      incidence in the islets of Langerhans of pre-diabetic ZDF rats given the
      compound, as compared to those not given MCC-555, as well as decreasing the
      accumulation of nitrate/nitrite within the pancreas.

PMID- 12801283
TI  - Pathogenesis of axonal dystrophy and demyelination in alphaA-crystallin
      expressing transgenic mice.
AB  - We recently described a transgenic mouse strain overexpressing hamster alphaA
      crystallin, a small heat shock protein, under direction of the hamster vimentin
      promoter. As a result myelin was degraded and axonal dystrophy in both central
      nervous system (especially spinal cord) and peripheral nervous system occurred.
      Homozygous transgenic mice developed hind limb paralysis after 8 weeks of age and
      displayed progressive loss of myelin and axonal dystrophy in both the central and
      peripheral nervous system with ongoing age. Pathologically the phenotype
      resembled, to a certain extent, neuroaxonal dystrophy. The biochemical findings
      presented in this paper (activity of the enzymes superoxide dismutase, catalase
      and transglutamase, myelin protein zero expression levels and blood sugar levels)
      confirm this pathology and exclude other putative pathologies like Amyothrophic
      Lateral Sclerosis and Hereditary Motor and Sensory Neuropathy. Consequently, an
      excessive cytoplasmic accumulation of the transgenic protein or a disturbance of
      the normal metabolism are considered to cause the observed neuropathology.
      Therefore, extra-ocular alphaA-crystallin-expressing transgenic mice may serve as
      a useful animal model to study neuroaxonal dystrophy.

PMID- 12801284
TI  - Interleukin-4-expressing plasmid DNA inhibits reovirus type-2-triggered
      autoimmune insulitis in DBA/1 J suckling mice.
AB  - In this study we have examined the effect of systemic administration of T helper
      (Th) 2 cytokines on reovirus type-2 (Reo-2)-triggered Th1-mediated autoimmune
      insulitis with impaired glucose tolerance (IGT) in DBA/1J suckling mice. We have
      demonstrated clearly that the systemic administration of both interleukin (IL)-4
      expressing plasmid DNA (pIL-4) and recombinant IL-4 (rIL-4) inhibited the
      development of insulitis with IGT in a dose dependent manner as compared to
      untreated groups in Reo-2-infected DBA/1J suckling mice. The inhibitory effects
      of IL-4 on the development of insulitis with IGT and the advantages of pIL-4 as
      compared to rIL-4 in this model are discussed.

PMID- 12801285
TI  - Scanning electron microscopic study of the cleaning ability of chlorhexidine as a
      root-canal irrigant.
AB  - AIM: To evaluate in vitro the cleaning of root-canal walls after irrigation with
      different irrigants. METHODOLOGY: A total of 36 recently extracted human teeth
      were divided into four experimental groups according to the irrigating solution
      used: saline; 2% chlorhexidine; 2.5% sodium hypochlorite; and 2.5% sodium
      hypochlorite + EDTA. The cleaning of the apical, middle and coronal thirds of the
      root canals was evaluated by scanning electron microscope examination using a 4
      point scoring system. RESULTS: The best cleaning was obtained using 2.5% sodium
      hypochlorite and EDTA, followed by 2.5% sodium hypochlorite only (P < 0.05),
      whose cleaning was similar to chlorhexidine only in the cervical third. Cleaning
      by saline and 2% chlorhexidine was worse than the other two groups and was
      similar in all thirds. Better cleaning was found in the cervical and middle
      thirds for all groups with the worst results in the apical third. CONCLUSIONS:
      The apical third of the root canals was not cleaned as well as the middle and
      coronal thirds. Cleaning by chlorhexidine and saline was inferior compared to the
      cleaning by sodium hypochlorite with and without EDTA.

PMID- 12801286
TI  - Age-related changes in blood capillary endothelium of human dental pulp: an
      ultrastructural study.
AB  - AIM: To describe the ultrastructural changes that occur in pulpal blood
      capillaries as a result of ageing. METHODOLOGY: Thirty samples of healthy dental
      pulps were obtained from functional human permanent teeth. Two age groups were
      examined: young (10-17 years) and old (>60 years). The teeth were extracted under
      local anaesthesia using mepivacaine without adrenaline (Scandonest 3%, Septodont,
      Saint-Maur des Fosses, France) and split longitudinally in a bench press. The
      pulps were gently removed, immersed in fixative solution, sectioned and processed
      by conventional transmission electron microscopic techniques. Micrographs were
      taken from the endothelium, and the whole capillary area of each vessel was
      examined. RESULTS: In young pulps, the endothelial cell layer was characterized
      by the presence of numerous pinocytotic vesicles and microvesicles, RER cisterns,
      free ribosomes, a small Golgi complex, centrioles, microtubules, microfilaments
      and mitochondria. In the endothelial cell cytoplasm of older pulpal vessels,
      pinocytotic vesicles and microvesicles, as well as microfilaments, were more
      numerous. In addition, lipid-like vacuoles, monogranular glycogen granules and
      extensive Golgi complexes with dilated cisterns were also present. Weibel-Palade
      bodies were observed in both age groups without showing variations related with
      age. CONCLUSIONS: The results obtained in capillaries of aged pulpal tissue
      suggest that the endothelium experiences morphological changes that could be
      associated with advancing age.

PMID- 12801287
TI  - Immunolocalization of bone extracellular matrix proteins (type I collagen,
      osteonectin and bone sialoprotein) in human dental pulp and cultured pulp cells.
AB  - AIM: To simultaneously analyse the expression of type I collagen, osteonectin and
      bone sialoprotein (BSP) in human dental pulp of different ages. METHODOLOGY:
      Cultured dental pulp fibroblasts (FP1 cell line), pulps from dental germs with
      incomplete root formation (n = 4) and pulps of erupted teeth with total root
      formation (n = 4) were used. Bone proteins were searched by immunohistochemistry
      and immunofluorescence using polyclonal antibodies and compared among the three
      groups assessed. RESULTS: Immunohistochemistry detected the three proteins in
      dental pulp tissue, as it labelled extracellular matrix, predentine and
      odontoblasts. The BSP label was weaker, when compared to both type I collagen and
      osteonectin. The presence of type I collagen was more evident in pulps from
      erupted teeth, when compared to germ dental pulps. On the other hand, a strong
      expression of osteonectin in germ dental pulps was observed. CONCLUSIONS:
      Regardless of the degree of maturation, dental pulps present type I collagen,
      osteonectin and BSP in the extracellular matrix (ECM) and in the odontoblastic
      layer. Thus, the results suggest that these proteins are related to the
      production and mineralization of dentine.

PMID- 12801288
TI  - Interactions of ethylenediamine tetraacetic acid with sodium hypochlorite in
      aqueous solutions.
AB  - AIM: To evaluate interactions of ethylenediamine tetraacetic acid (EDTA) with
      sodium hypochlorite (NaOCl). METHODOLOGY: Solutions consisting of 8.5% EDTA and
      0.5% NaOCl were compared to a 1 : 1 (w/w) mixture of 17% EDTA and 1% NaOCl for
      their calcium-chelating, tissue-dissolving, and antimicrobial properties. Amounts
      of available chlorine were determined in the EDTA/NaOCl solutions with an
      iodine/thiosulphate titration method. Calcium chelation capacity was titrated
      with a pure calcium solution using a murexide indicator. Weight loss of porcine
      palatal mucosal specimens incubated in the test solutions was measured over time.
      Antimicrobial potential of pure solutions and the combination was recorded using
      an agar diffusion test in plates incubated with Enterococcus faecalis or Candida
      albicans. RESULTS: The presence of hypochlorite had little effect on the calcium
      chelating ability or on the antimicrobial potential of EDTA. Available chlorine
      content decreased to 0.06% in the combined EDTA-NaOCl solution compared to 0.50%
      in an equivalent NaOCl mixture with deionized water. The EDTA-NaOCl solution did
      not dissolve more tissue than an equivalent pure EDTA solution at any time
      (anova, P > 0.05). CONCLUSIONS: Ethylenediamine tetraacetic acid retained its
      calcium-complexing ability when mixed with NaOCl, but EDTA caused NaOCl to lose
      its tissue-dissolving capacity and virtually no free chlorine was detected in the
      combinations. Clinically, this suggests that EDTA and NaOCl should be used
      separately. In an alternating irrigating regimen, copious amounts of NaOCl should
      be administered to wash out remnants of the EDTA.

PMID- 12801289
TI  - Technical quality of root canal treatment in Taiwan.
AB  - AIM: To evaluate the current technical quality of root canal treatment (RCT) in
      Taiwan. METHODOLOGY: A total of 1085 RCT cases, randomly selected from a large
      sample and representative of the Taiwanese population from April to September
      2000, were evaluated by eight endodontic specialists. The qualitative evaluation
      of RCT cases was based on two variables: length of the root filling and density
      of the obturation. A root canal with both adequate filling length (the apical
      termination of the root filling within 2 mm of the radiographic apex) and
      complete obturation (no lateral or apical canal lumen visible in the apical one
      third of the root canal) was defined as having good-quality endodontic work
      (GQEW). A tooth was defined as having a GQEW when all its canals were categorized
      as GQEW. RESULTS: From a total of 1867 root canals, overfilling occurred in 235
      (12.6%), adequate filling length in 1152 (61.7%), underfilling in 466 (25.0%) and
      no filling in 12 (0.6%). Of the 1867 root canals, 710 (38.0%) demonstrated
      complete obturation and 1157 (62%) demonstrated incomplete obturation. GQEW was
      found in 650 (34.8%) root canals and 329 (30.3%) teeth. The percentage of teeth
      with GQEW in hospital cases (38.1%) was significantly greater (P < 0.001) than
      that in private clinic cases (24.3%). In addition, the frequency of teeth with
      GQEW in the anterior teeth (40.4%) or in the premolars (33%) was significantly
      greater (P < 0.001) than that in the molars (18.4%). CONCLUSIONS: Approximately
      70% of the teeth receiving RCT in Taiwan were either of inadequate filling length
      or sealing density.

PMID- 12801290
TI  - Comparison of antibacterial and toxic effects of various root canal irrigants.
AB  - AIM: To compare the antibacterial properties and toxicity of 5.25% sodium
      hypochlorite (NaOCl), 2% chlorhexidine gluconate and 0.2% chlorhexidine gluconate
      plus 0.2% cetrimide (Cetrexidin); Vebas, San Giuliano, Milan, Italy).
      METHODOLOGY: The antibacterial effects of the irrigants in vitro were examined
      after 5 min and 48 h in freshly extracted human teeth with single roots, whose
      canals were infected by Enterococcus faecalis ATCC 29212. In a separate in vivo
      study, bacterial culture samples were collected before treatment from the
      infected root canals of deciduous teeth containing necrotic pulp tissue.
      Irrigants were used to clean the canals which were then left empty for 48 h.
      Aerobic/facultative anaerobic and anaerobic bacterial growth were compared before
      and 48 h after irrigation. Finally, the toxic effects of the irrigants were
      assessed by injecting them into the subcutaneous tissues of rats. The
      inflammatory reactions that occurred 2 h, 48 h and 2 weeks after the injections
      were evaluated. RESULTS: In the laboratory study, the 2% chlorhexidine gluconate
      and Cetrexidin were significantly more effective on E. faecalis than the 5.25%
      NaOCl at 5 min (P < 0.05). Similarly, in the in vivo study, 2% chlorhexidine
      gluconate and Cetrexidin were significantly more effective on anaerobic bacteria
      than the 5.25% NaOCl at 48 h (P < 0.05). At the end of 2 weeks, the toxicity of
      the NaOCl solution was greater than that of the other irrigants (P < 0.05).
      CONCLUSIONS: Cetrexidin and 2% chlorhexidine gluconate were more effective, and
      had more residual antibacterial effects and lower toxicity than 5.25% NaOCl
      solution.

PMID- 12801291
TI  - Preliminary in vitro evaluation of Carisolv as a root canal irrigant.
AB  - AIM: To test the null hypothesis that Carisolv is no better than PBS in removing
      organic debris from uninstrumented root canals. METHODOLOGY: The pulps of two
      uniform groups of 36 immature, sheep mandibular incisors were grossly removed
      with barbed broaches immediately prior to the study. Roots in group 1 were
      irrigated with phosphate buffered saline (PBS), strong sodium hypochlorite (4.5%)
      or Carisolv without ultrasonic agitation, whilst in group 2 the same irrigants
      were activated with ultrasound. Canal walls were exposed to irrigants for 10, 20
      or 30 min at 37 degree C. In group 2, ultrasound was applied for 30 s at 2, 5 and
      7 min within each 10 min incubation period. After washing irrigants free and
      immersion in fixative, all teeth were split longitudinally, critical point dried
      and sputter coated for SEM analysis. SEM photomicrographs were recorded of
      representative areas in the coronal, middle and apical canal thirds and debris
      scored by a single assessor against a five-point scale. Intraobserver reliability
      was assessed by Cohens kappa scores and debris scores analysed by the non
      parametric Kruskal-Wallis test at P < 0.05. RESULTS: Sodium hypochlorite was
      significantly better than Carisolv and PBS in cleaning root canals (P < 0.0001),
      whether or not ultrasound was applied. Carisolv was shown to clean canals better
      than PBS, again whether or not ultrasound was applied (P = 0.01). Both incubation
      time and ultrasound enhanced the action of Carisolv (P < 0.001) whilst the
      activity of PBS was not significantly improved by exposure time or the
      application of ultrasound. Kappa scores of 0.90-0.95 indicated excellent
      consistency in debris scoring. CONCLUSIONS: Within the limitations of this
      preliminary study (i). Carisolv cleaned root canals better than PBS and shows
      promise as an adjunct to root canal preparation; (ii). the action of Carisolv was
      enhanced by incubation times beyond 20 min whether or not ultrasound was applied;
      (iii). sodium hypochlorite solution remains the gold standard endodontic
      irrigant, provided that it is used with care and is contained in the canal
      system.

PMID- 12801292
TI  - Clinical characteristics, prognostic factors and multidrug-resistance related
      protein expression in 36 adult patients with acute promyelocytic leukemia.
AB  - We report on a single-center experience about the characteristics and outcome of
      36 acute promyelocytic leukemia (APL) patients observed at our Department of
      Hematology between 1990 and 2002. The expression, of multidrug-resistance (MDR)
      associated proteins (PGP, LRP, MRP1) was also analyzed. There were 12 males and
      24 females (median age 37 yr), 89% (32 of 36) with classic morphology, and 11%
      (four of 36) with a microgranular variant. Risk class (according to
      GIMEMA/PETHEMA): 25% (nine of 36) high risk (HR), 53% (nineteen of 36)
      intermediate risk (IR), 22% (eight of 36) low risk (LR). PGP, LRP, and MRP1
      expression at onset and at first relapse was low. CD33 antigen expression was
      high in all cases. The patients were treated according to GIMEMA protocols
      (LAP0389 and AIDA) including ATRA in induction in 75% (27 of 36) of cases and 94%
      (34 of 36) achieved a complete remission (CR) after induction therapy while 6%
      (two of 36) died early (DDI) of hemorrhage. OUTCOME: 71% (24 of 34) of evaluable
      patients remain in CR at a median follow-up of 57 months (range 4-158 months)
      while 29% (10 of 34) relapsed at a median time of 12 months (range 8-43 months)
      and, of them, eight of 10 died early. The majority of patients that relapsed were
      in high-risk group. The overall survival (OS) of the whole population at 32
      months was 66% and the DFS at 42 months was 62%. A statistically significant
      difference in terms of DFS was observed between HR and IR/LR patients (P = 0.04
      by log-rank). DFS was not affected by age, sex, Hb levels, karyotype, and BCR
      isoform. At conclusion, our data confirm that despite the high rate of success
      with ATRA plus chemotherapy as induction (more than 90% of CR), about 30% of APL
      patients have a relapse (without a long-lasting second remission) and underline
      the importance of patient stratification in distinct risk groups at diagnosis in
      order to better adapt the type and intensity of treatment (risk-adapted therapy).
      Taking into account the high expression of CD33 and the low expression of MDR
      proteins in APL, new and investigational approaches like gemtuzumab-ozogamicin,
      with or without ATRA and other new drugs, should be strongly considered
      expecially in HR APL.

PMID- 12801293
TI  - Effects of angiogenic regulators on in vitro proliferation and cytokine secretion
      by native human acute myelogenous leukemia blasts.
AB  - Angiogenesis seems to be important in the pathogenesis of acute myelogenous
      leukemia (AML). The endothelial cell proliferation and microvessel formation are
      regulated by a wide range of soluble mediators, including angiogenin,
      angiopoietin-2, basic fibroblast growth factors, vascular endothelial growth
      factor (VEGF), VEGF-D, angiostatin and endostatin. In the present study, it has
      been investigated whether these mediators have an additional direct effect on the
      proliferation and cytokine release by native human AML blasts. AML cells derived
      from a large group of consecutive patients were investigated. All these mediators
      could alter the proliferation and cytokine release [interleukin (IL) 1beta, IL6,
      IL8, tumor necrosis factor alpha] for a minority of patients. Alteration of
      spontaneous proliferation by at least one mediator was detected in five of 38
      patients; whereas, altered cytokine (Flt3-ligand, granulocyte-macrophage colony
      stimulating factor, stem cell factor)-dependant proliferation was observed for 10
      patients. Growth enhancement was most frequently observed, whereas growth
      inhibition was uncommon. The effects on AML blast proliferation were often
      dependant on or were modulated by the presence of the three hematopoietic growth
      factors. Based on the present results, it is concluded that angioregulatory
      mediators have additional growth-enhancing effects directly on the AML blasts for
      certain patients. However, based on the results from this investigation and
      previous studies it is suggested that their major contribution to the
      pathogenesis of AML is through their effects on regulation of bone marrow
      angiogenesis, and future studies of these mediators in AML should probably focus
      on these effects.

PMID- 12801294
TI  - Chronic basophilic leukemia: a distinct clinico-pathologic entity?
AB  - OBJECTIVE: We sought to better define a group of rare and poorly understood
      myeloproliferative disorders that are characterized by prominent chronic
      basophilia in the absence of the Philadelphia chromosome (Ph) or its molecular
      equivalent. METHODS: We screened our institution's electronic database from 1975
      onwards, and identified four such cases. Clinical data and bone marrow pathology
      were carefully reviewed for these patients. RESULTS: Two patients had prominent
      manifestations of basophil mediator-release and another presented with pituitary
      dysfunction. Bone marrow examination uniformly revealed trilineage hyperplasia
      with basophilia and eosinophilia, dysplastic megakaryocytic hyperplasia, and the
      absence of megakaryocyte clustering. An abnormal pattern of atypical mast cells
      was noted in two cases. While disease palliation was effectively achieved with
      hydroxyurea for one patient, transformation to acute myeloid leukemia was
      eventually observed in this case. Another patient has achieved long-term disease
      free survival after undergoing allogeneic stem cell transplantation. CONCLUSIONS:
      Our observations reveal a striking pathologic similarity among all four cases,
      and suggest this disease, which may be aggressive with the potential to transform
      into acute leukemia, to possibly represent a distinct clinico-pathologic entity
      (chronic basophilic leukemia).

PMID- 12801295
TI  - Fludarabine plus cyclophosphamide for the treatment of advanced chronic
      lymphocytic leukemia.
AB  - OBJECTIVES: Therapeutic results in advanced chronic lymphocytic leukemia (CLL)
      are still unsatisfactory in terms of complete remission achievement and duration,
      in spite of the extensive use of purine analogs. The objective of this study was
      to describe the clinical characteristics and treatment results from a series of
      32 patients managed with a therapeutic program based on the combination of
      fludarabine and cyclophosphamide (CTX). METHODS: Thirty-two patients (median age
      63 yr, range 42-75 yr) with newly diagnosed (47%) or refractory-relapsed (53%)
      CLL were programmed to receive six courses of a 3-d combination of fludarabine at
      30 mg/m2/d plus CTX at 300 mg/m2/d. Refractory-relapsed patients had previously
      received different chemotherapy lines from 1 to 5. RESULTS: Fourteen of 32 (44%)
      patients achieved a complete remission, 16 (50%) obtained partial remission and
      two (6%) failed to respond. The CR rate was higher in untreated patients; in
      particular, CR was achieved in nine of 15 (60%) newly diagnosed cases as opposed
      to five of 17 (29%) among pretreated patients. Toxicity was caused by
      myelosuppression and/or infections in most cases. After a median follow-up of 24
      months (range 8-48 months), 20 of 32 patients (62%) are alive, and 14 of 32 (44%)
      are free from progression. Median overall survival and median time to progression
      were 35 and 25 months, respectively. CONCLUSION: The combination of fludarabine
      with CTX is effective in advanced CLL with acceptable toxicity, either as first
      line therapy or in refractory-relapsed patients. In particular, a considerable
      rate of complete remission can be achieved in untreated patients.
      Myelosuppression represents the major side-effect.

PMID- 12801296
TI  - Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells
      from umbilical cord blood.
AB  - The activity of natural killer (NK) cells in human umbilical cord blood (CB) has
      been reported to be low, compared with that in adult peripheral blood (PB) in
      vitro. To examine the cause of this, after dividing the CD56+/CD3- cells in CB
      and PB into CD56bright and CD56dim NK cells, the NK cell activities and the
      expression of various surface antigens were assayed for each fraction. The NK
      cell activity of CD56dim NK cells in CB was significantly lower than that in PB
      (P = 0.0003), whereas, there was no significant difference between the NK cell
      activity of CD56bright NK cells in PB and CB. The expression levels of adhesion
      molecules (CD2, CD11a, CD18, DNAX accessory molecule-1), CD16, and CD57 for
      CD56dim NK cells in CB were significantly lower than those in PB, and
      approximately one-third of CB CD56dim NK cells were capable of forming conjugates
      with K562 cells, compared with PB CD56dim NK cells. Furthermore, the inhibition
      of both the NK cell activities and binding of CD56dim NK cells in PB and CB by
      monoclonal antibody against each of these adhesion molecules suggests that they
      play an important role in NK cell activity. These findings show that the low NK
      cell activity in CB is caused by the low NK cell activity of CD56dim NK cells and
      that the low expression level of adhesion molecules on CB CD56dim NK cells may
      contribute to this low NK cell activity.

PMID- 12801297
TI  - Identification of an inframe deletion and a missense mutation in the factor XIIIA
      gene in two Turkish patients.
AB  - We report two novel mutations in factor XIIIA (FXIIIA) gene that caused
      congenital factor XIII deficiency in two unrelated patients. The first
      alteration, a missense mutation Leu235Arg in exon 6 of FXIIIA gene, is located in
      the putative calcium-binding part of the core domain of the enzyme. Replacement
      of non-polar hydrophobic leucine residue with positively charged arginine residue
      is likely to effect protein folding thus destabilizing the molecule. The second
      mutation is a 3-bp deletion in exon 14 of FXIIIA gene. This deletion is located
      in beta barrel 2 domain of the protein and results in translation of an aberrant
      FXIIIA molecule that lacks lysine residue either at positions 677 or 678. As this
      inframe deletion is located in a direct repetetive sequence of AAGAAG, that codes
      for two lysine residues, the exact location of deletion could not be detected.

PMID- 12801298
TI  - Haemoglobin during pregnancy: relationship to erythropoietin and haematinic
      status.
AB  - OBJECTIVE: To investigate the effect of haematinic status on erythropoietin
      throughout pregnancy in order to assess whether haematinic supplementation is
      appropriate for all pregnant women or should be reserved for individuals in whom
      deficiency has been identified. METHODS: A prospective, repeated-measures,
      longitudinal study of 263 women enrolled at an antenatal clinic in a district
      general hospital who received standard obstetric management including haematinic
      supplements. Haematological indices, iron status, folate and B12 status, and
      erythropoietin levels were measured by standard methods at scheduled intervals
      throughout pregnancy. The relationships between the measurements were analysed
      using statistical models which took into account the serial correlation between
      repeated measurements on the same individuals. RESULTS: Erythropoietin levels
      rose throughout pregnancy from a mean of 22.8 mU/mL at booking to 43.7 mU/mL at
      38 wk. There was a significant relationship between erythropoietin levels and
      haemoglobin, ferritin, TIBC and folate. The relationship was strongest between
      erythropoietin and haemoglobin. Erythropoietin levels were influenced by parity
      but not maternal age. CONCLUSION: Haematinic levels, particularly iron are
      related to the rise in serum EPO which occurs during pregnancy. Therefore,
      haematinic deficiency in pregnancy will result in increased stimulation of
      erythroid progenitor cells by erythropoietin. While haematinic supplementation is
      not always prescribed throughout pregnancy, haematinic status must be assessed on
      an individual basis and supplementation provided as required.

PMID- 12801299
TI  - Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron
      stores and the prevalence of iron deficiency and iron overload.
AB  - BACKGROUND AND OBJECTIVES: From 1954 to 1986, flour in Denmark was fortified with
      30 mg carbonyl iron per kilogram. This mandatory enrichment of cereal products
      was abolished in 1987. The aim was to evaluate iron status in the Danish female
      population before and after abolishment of iron fortification. METHODS: Iron
      status, serum ferritin and haemoglobin, was assessed in population surveys in
      1983-1984 comprising 1221 Caucasian women (1089 non-blood-donors, 130 donors) and
      in 1993-1994 comprising 1261 women (1155 non-blood-donors, 104 donors) equally
      distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey,
      median ferritin values in the four age cohorts in non-blood-donors were 44, 57,
      84 and 80 microg/L, and in the 1994 survey 40, 67, 97 and 95 microg/L,
      respectively. In 1984, premenopausal women had median ferritin of 43 microg/L and
      in 1994 of 39 microg/L (NS). In 1984, postmenopausal women had median ferritin of
      75 microg/L and in 1994 of 93 microg/L (P < 0.0001). The prevalence of depleted
      iron stores (ferritin < 16 microg/L) was not significantly different in 1984 and
      1994 either in premenopausal or in postmenopausal women. The prevalence of small
      + depleted iron stores (ferritin <or=32 microg/L) was not significantly different
      in 1984 compared with 1994 either in premenopausal women (35.8% vs. 41.0%) (P =
      0.15) or in postmenopausal women (9.7% vs. 7.4%) (P = 0.15). There was no
      significant difference between the two surveys concerning the prevalence of iron
      deficiency anaemia (ferritin <13 microg/L and haemoglobin <5th percentile for
      iron replete women). From 1984 to 1994, the prevalence of iron overload (ferritin
      >300 microg/L) was unchanged in premenopausal women and had increased from 2.4%
      to 5.5% in postmenopausal women (P = 0.003). During the study period there was an
      increase in body mass index both in premenopausal and postmenopausal women (P =
      0.06 and P = 0.008). Postmenopausal women displayed an increase in alcohol
      consumption (P < 0.0001) and a decrease in tobacco smoking (P < 0.001). In
      premenopausal women, there was a marked increase in the use of non-steroid anti
      inflammatory drugs (P < 0.0001) in the study period, while this was unchanged in
      postmenopausal women. In premenopausal blood donors, median ferritin decreased
      from 1984 to 1994 (36 microg/L vs. 24 microg/L, P < 0.06). In postmenopausal
      blood donors, ferritin was not significantly different from 1984 to 1994 (50
      microg/L vs. 41 microg/L, P = 0.15). CONCLUSION: Abolition of iron fortification
      reduced the median dietary iron intake in Danish women from 12 to 9 mg/d. Despite
      the absence of food iron fortification, from 1984 to 1994, body iron stores were
      unchanged in premenopausal women, whereas iron stores and the prevalence of iron
      overload in postmenopausal women had increased significantly. The reason appears
      to be the changes in dietary habits with a lower consumption of dairy products
      and eggs, which inhibit iron absorption, and a higher consumption of alcohol,
      meat and poultry, containing heme iron and enhancing iron absorption.

PMID- 12801300
TI  - An unusual case of primary effusion lymphoma in a HIV-negative patient not
      pathogenetically associated with HHV8.
AB  - The development of an unusual case of primary pleural effusion in a 90-year-old
      human immunodeficiency virus (HIV)-negative Japanese woman with no identifiable
      tumor mass has been described. Pleural effusion specimens contained large diffuse
      lymphoma cells, with the phenotype and genotype of a B-cell lineage (positive for
      CD20, CD79a and clonal rearrangement of Ig heavy chain) and the c-myc gene
      rearrangement, but were negative for T-cell markers (CD45RO and CD3). The patient
      was negative for human herpes virus 8 (HHV8), Epstein-Barr virus (EBV) and
      hepatitis C virus (HCV), as well as human T-cell lymphotropic virus type-1 (HTLV
      1). The patient died of respiratory failure 5 months after the diagnosis of
      primary effusion lymphoma (PEL), and an autopsy was performed. Autopsy findings
      revealed no evidence of tumor mass or bone marrow involvement of lymphoma cells.
      This case has been considered as a PEL in a HIV-, HHV8-, EBV- and HCV-negative
      patient. Although cytomorphology of lymphoma cells was classified as large-cell
      lymphoma in this case, it is interesting that the present case may represent an
      unusual subset of Burkitt-like disease because of clear B-cell phenotype and c
      myc gene rearrangement.

PMID- 12801301
TI  - Post-transfusion purpura (PTP) and disseminated intravascular coagulation (DIC).
AB  - A 47-yr-old female with acute pancreatitis received four units of fresh frozen
      plasma because of subtle signs of disseminated intravascular coagulation (DIC).
      Seven days later, she developed severe thrombocytopenia. Serological studies
      demonstrated antibodies against HPA-1a together with pan-reactive antibodies
      against platelet glycoproteins (GPIIb-IIIa, GPIb-IX and GPIa-IIa), which was
      consistent with the diagnosis of PTP. The patient was treated with platelet
      transfusions, corticosteroids and intravenous immunoglobulin (IVIG) without
      permanent beneficial effect. After treatment with plasma exchange the platelet
      count increased to normal values.

PMID- 12801302
TI  - Mycobacteria and atopy, 6 years later: a fascinating, still unfinished, business.

PMID- 12801303
TI  - Do anti-leukotriene agents inhibit asthmatic inflammation?

PMID- 12801304
TI  - The cow's milk protein-specific T cell response in infancy and childhood.

PMID- 12801305
TI  - Absence of association between delayed type hypersensitivity to tuberculin and
      atopy in children in The Gambia.
AB  - BACKGROUND: An inverse association between delayed type hypersensitivity to
      tuberculin and atopy has been observed in children, suggesting that exposure to
      mycobacteria may influence the immune response to allergens. OBJECTIVE: To
      investigate the relationship between tuberculin responses and atopy in children
      living in three different environments in The Gambia. METHODS: In this cross
      sectional study a total of 507 school-aged children were recruited from rural,
      urban poor or urban affluent communities. They were assessed for skin responses
      to five common allergens and tuberculin, presence of bacille Calmette-Guerin
      (BCG) scar, presence of intestinal parasites, and total serum IgE. Atopy was
      defined as the presence of a skin prick test response > or = 3 x 3 mm to at least
      one allergen. RESULTS: The overall prevalence of atopy was 33% but there was a
      significant variation among the three study groups. The prevalence of atopy was
      22% in urban poor, 36% in urban affluent, and 43% in rural children. Controlling
      for potential confounding factors, children in the rural community had a
      significantly higher odds ratio, 3.3 (95% confidence interval 1.8-6.0) of being
      atopic than children from the urban poor community. No association between atopy
      and tuberculin response or BCG scar was observed in any of the three groups.
      Serum IgE levels were higher among children of the urban poor group but were not
      associated with tuberculin response or BCG scar in any of the groups. CONCLUSION:
      Environmental factors have an important influence on the development of atopy in
      children in The Gambia but delayed type hypersensitivity to tuberculin is not a
      protective factor.

PMID- 12801306
TI  - Neonatal head circumference, neonatal weight, and risk of hayfever, asthma and
      eczema in a large cohort of adolescents from Sheffield, England.
AB  - BACKGROUND: Neonatal physical characteristics, including head circumference and
      birth weight, have been hypothesized to be markers of in utero thymic
      development. Greater head circumference and lower birth weight have been linked
      in previous studies to subsequent development of asthma, and greater birth weight
      has been associated with subsequent development of eczema. OBJECTIVE: To
      investigate potential associations between neonatal head circumference and weight
      and hayfever, asthma and eczema in a cohort of adolescents from Sheffield,
      England. METHODS: Responses to a questionnaire inquiring about physician
      diagnosed hayfever, asthma and eczema among adolescents in Sheffield, England,
      were linked to previously recorded measurements of weight at birth and at 1 month
      and head circumference at 1 month. Logistic regression methods were used to
      relate diagnoses to neonatal measurements and potential confounders. RESULTS: The
      cohort consisted of 10,809 adolescents, of whom 16.5% reported hayfever, 18.0%
      asthma, and 16.2% eczema. After adjusting for sex, age at the time of the
      questionnaire, maternal age and gestational age at birth, number of older and
      younger siblings, time since birth of next older sibling, neonatal sickness, type
      of neonatal feeding, and maternal and paternal educational backgrounds, hayfever
      was the only disease associated with neonatal measurements. Comparing the highest
      with the lowest fifths of distributions, lifetime prevalence of hayfever was
      positively associated with neonatal head circumference (adjusted odds ratio 1.23,
      95% CI 1.03 to 1.47) and with birth weight (1.17, 0.99 to 1.39). Hayfever was
      inversely related to the ratio of head circumference to birth weight (0.89, 0.75
      to 1.05) and to gestational age. The associations with head circumference and
      birth weight were not substantially altered by further adjustment for gestational
      age. CONCLUSION: Greater neonatal head circumference may be associated with an
      increased risk of hayfever, but the inverse relationship between hayfever
      prevalence and the ratio of head circumference to birth weight challenges the
      prior hypothesis that greater head circumference relative to body mass reflects
      abnormal thymic development in utero, increasing the likelihood of allergic
      sensitization.

PMID- 12801307
TI  - Relationships of allergic sensitization, total immunoglobulin E and blood
      eosinophils to asthma severity in children of the EGEA Study.
AB  - BACKGROUND: Although allergy is highly associated with childhood asthma, it is
      not well known if there is a relationship between the intensity of allergic
      sensitization and asthma severity. OBJECTIVE: The objectives of the study were to
      examine the relationships between several markers of allergy and asthma severity
      in asthmatic children included in the Epidemiological study on the Genetics and
      Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA). METHODS:
      The population comprised 216 asthmatic children below 16 years of age. Total IgE
      and blood eosinophil counts were measured and skin prick tests to 11
      aeroallergens were performed. The intensity of the allergic sensitization was
      assessed by the number of positive skin prick tests and by skin weal sizes.
      Asthma severity was measured with four criteria: a clinical severity score,
      history of hospitalization for asthma, FEV1% predicted and inhaled steroid use in
      the last 12 months. RESULTS: Most of the children were sensitized to at least one
      aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for
      a tendency for a more severe clinical score in non-atopic children. The type and
      intensity of the allergic sensitization were not associated with any criteria of
      asthma severity. Total IgE was significantly increased in children treated with
      inhaled corticosteroids and in children ever hospitalized for asthma (P-values
      0.009 and 0.04, respectively). Eosinophil counts were not related to asthma
      severity. CONCLUSION: Our results suggest that severe childhood asthma may be
      related to a high level of total IgE but not to blood eosinophil counts. The lack
      of positive relationships between both atopy and the intensity of allergic
      sensitization with asthma severity supports the hypothesis of different risk
      factors being associated with asthma and with the severity of asthma.

PMID- 12801308
TI  - Normative data for total serum immunoglobulin E measurements in children of three
      ethnicities.
AB  - BACKGROUND: It is about 20 years since IgE measurements were published for
      children without atopic disease. It is possible that the recent increase in
      atopic disease is reflected in altered measurements in subjects who have no
      clinical expression of atopy. If the measurement of IgE is to be used as a marker
      for atopy to characterize disease categories, contemporary normative data must be
      available. OBJECTIVE: To measure total serum IgE in healthy children of three
      ethnicities born and living in an inner city environment. METHODS: Subjects were
      aged 1 to < or = 12 years, of Afro-Caribbean, Bangladeshi and white British
      ethnicities, with no personal history of current atopic disease. An extra 1 mL of
      blood for the measurement of total serum IgE was collected when blood was taken
      for other purposes or when a surgical procedure was being undertaken. RESULTS:
      Measurements were taken from 151 boys (median age 5.4 years) and 106 girls
      (median age 6.0 years), who included 127 Bangladeshis, 58 Afro-Caribbeans and 72
      white British children. Measurements increased with age but were not related to
      gender or ethnicity. The data were significantly higher than previous
      measurements by sixfold. CONCLUSION: These contemporary normative data allow the
      generation of z scores for total IgE measurements for clinical or epidemiological
      use.

PMID- 12801309
TI  - Caesarean section increases the risk of hospital care in childhood for asthma and
      gastroenteritis.
AB  - OBJECTIVE: To investigate if caesarean section (CS) increases the risk for
      childhood asthma and gastroenteritis with reference made to children born with
      vaginal delivery (VD). METHODS: Retrospective study of data from linked Swedish
      medical service registers--Medical Birth Registry (MBR) and Hospital Discharge
      Registry (HDR). Data were obtained from women without any background/perinatal
      morbidity noted, and from children without any neonatal complications. Children
      that had reached at least 1 year of age and were found in the HDR were considered
      as cases, whereas children not found in the HDR or hospitalized for other causes
      than asthma or gastroenteritis were defined as controls. Odds ratios (OR)
      stratified for year of birth, maternal age, parity and smoking in early pregnancy
      were calculated. Investigations were made comparing the risk for in hospital
      treatment for asthma or gastroenteritis in CS children and in VD siblings of CS
      children. The overall inpatient morbidity in CS and VD children were also
      investigated. RESULTS: The OR for asthma in CS children was 1.31 [95% confidence
      interval (CI) 1.23-1.40]. The same OR, 1.31, was found for gastroenteritis (95%
      CI 1.24-1.38). The OR for CS children having experienced both asthma and
      gastroenteritis was further increased (1.74, 95% CI 1.36-2.23). The risk for
      asthma in VD siblings of CS children was not significantly increased, whereas VD
      siblings experienced a slightly increased risk for gastroenteritis. CS children
      had an increased overall in hospital morbidity when compared to VD children.
      CONCLUSION: There is a significant increase of the risk for developing symptoms
      of asthma and/or gastroenteritis that motivates admission for hospital care in CS
      children older than 1 year. It is speculated that a disturbed intestinal
      colonization pattern in CS children may be a common pathogenic factor.

PMID- 12801310
TI  - Air filtration units in homes with cats: can they reduce personal exposure to cat
      allergen?
AB  - BACKGROUND: Domestic air filtration units have previously been shown to cause a
      dramatic fall in airborne pet allergen levels in homes with pets. Clinical trials
      of air filtration units, however, have failed to reveal a significant beneficial
      effect. Personal pet allergen exposure during air filtration unit use has never
      been measured. OBJECTIVE: To determine the effect of air filtration on inhaled
      cat allergen exposure in homes with cats. METHODS: Nasal air samplers were worn
      to measure personal cat allergen exposure. The study was carried out in five
      homes with cats on 4 separate days examining four experimental conditions (cat
      absent or present, air filtration off or on). The two operators collected four
      baseline samples and two 15-min samples/h over three consecutive hours. Cat
      allergen-bearing particles were detected by immunoblotting and allergen
      concentrations measured by amplified enzyme-linked immunosorbent assay (ELISA).
      RESULTS: There was a significant reduction in the quantity of the inhaled Fel d 1
      when the air cleaner was used with the cat in the room. Fel d 1 halo counts
      (detransformed means) were 29.3 at baseline, 11.8 after 1 h, 10.0 after 2 h and
      14.1 after 3 h, with no change on control days (P = 1.00). With the cat elsewhere
      in the house, a marginal, but statistically significant reduction was observed
      only after 3 h with the use of air cleaner (Fel d 1 halo count: baseline 12.4; 3
      h 5.5; P = 0.01). CONCLUSIONS: The use of air filtration units appears to result
      in a much smaller reduction of inhaled cat allergen exposure than suggested by
      previous studies using standard air samplers. Cat removal remains the best advice
      to cat-allergic patients who experience symptoms upon exposure.

PMID- 12801311
TI  - Early endotoxin exposure and atopy development in infants: results of a birth
      cohort study.
AB  - BACKGROUND: Exposure to endotoxin in childhood is currently discussed to protect
      from the development of allergic diseases. OBJECTIVE: To study the effect of
      early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis
      and wheezing until the age of 2 years in infants with different risk status in
      terms of parental atopy. METHODS: Data of 1942 infants of an ongoing birth cohort
      study were analysed by logistic regression. Endotoxin was measured in settled
      dust of the mothers' mattresses at infants' age of 3 months. Data on allergic
      symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization
      to common food and inhalant allergens was assessed by specific serum IgE.
      RESULTS: High endotoxin levels increased the risk of repeated wheeze [adjusted
      odds ratio (OR) for 4th exposure quartile (Q4) 1.52, 95% confidence interval (CI)
      1.08-2.14], but were associated with neither sensitization to food allergens nor
      atopic dermatitis. Stratification by parental atopy showed that there was an
      association of endotoxin exposure with incidence of repeated wheeze as well as
      with sensitization to inhalant allergens (P for trend = 0.008 and 0.044,
      respectively) only in infants with parental atopy, with the highest risk in the
      4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73;
      sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). CONCLUSION:
      Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to
      increase the risk of atopic reactions to inhalant allergens at the age of 2
      years, especially in infants at risk due to parental atopy. Our data disagree
      with an early protective effect of endotoxin on atopy development until the age
      of 2 years.

PMID- 12801312
TI  - Ozone-induced bronchial epithelial cytokine expression differs between healthy
      and asthmatic subjects.
AB  - BACKGROUND: Ozone (O3) is a common air pollutant associated with adverse health
      effects. Asthmatics have been suggested to be a particularly sensitive group.
      OBJECTIVE: This study evaluated whether bronchial epithelial cytokine expression
      would differ between healthy and allergic asthmatics after ozone exposure,
      representing an explanatory model for differences in susceptibility. METHODS:
      Healthy and mild allergic asthmatic subjects (using only inhaled beta2-agonists
      prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and
      filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h
      after exposure. Biopsies were embedded in GMA and stained with mAbs for
      epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, GRO-alpha,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), fractalkine and ENA
      78. RESULTS: When comparing the two groups at baseline, the asthmatic subjects
      showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the
      epithelial expression of IL-5, GM-CSF, ENA-78 and IL-8 increased significantly in
      asthmatics, as compared to healthy subjects. CONCLUSION: The present study
      confirms a difference in epithelial cytokine expression between mild atopic
      asthmatics and healthy controls, as well as a differential epithelial cytokine
      response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related
      cytokines and neutrophil chemoattractants shown in the asthmatic group may
      contribute to a subsequent worsening of the airway inflammation, and help to
      explain their differential sensitivity to O3 pollution episodes.

PMID- 12801313
TI  - Effects of mediator antagonism on mannitol and adenosine monophosphate
      challenges.
AB  - BACKGROUND: Airway hyper-responsiveness (AHR) to indirect stimuli is a useful non
      invasive surrogate inflammatory marker in the evaluation of asthma, while
      histamine and cysteinyl leukotrienes are important inflammatory mediators.
      OBJECTIVE: To evaluate AHR to indirect bronchoconstrictor stimuli and time taken
      to recover following single doses of montelukast 10 mg and desloratadine 5 mg in
      combination, montelukast 10 mg alone and placebo. METHODS: Fifteen mild-to
      moderate persistent asthmatics completed a randomized, double-blind, cross-over
      study. Patients received encapsulated montelukast 10 mg/desloratadine 5 mg
      combination, montelukast 10 mg alone and placebo, 10-14 h prior to challenge on
      two separate occasions. The mannitol threshold dose, AMP threshold concentration
      and recovery times after challenge were measured along with lung function.
      RESULTS: Compared to placebo, montelukast/desloratadine conferred improvements (P
      < 0.05) in adenosine monophosphate (AMP) threshold concentration and mannitol
      threshold dose: a 3.2-fold (95% CI 2.2-4.6) and 2.4-fold (95% CI 1.7-3.3)
      difference, respectively, while compared to montelukast this amounted to a 2.0
      fold (95% CI 1.2-3.4) and 1.5-fold (95% CI 1.1-2.4) improvement, respectively.
      Montelukast was not significantly different from placebo. Both
      montelukast/desloratadine and montelukast compared to placebo, shortened recovery
      following both challenges (P < 0.05): a 27-min (95% CI 17-37) and 29-min (95% CI
      20-36) reduction, respectively, for AMP, and a 27-min (95% CI 17-37) and 26-min
      (95% CI 17-35) reduction, respectively for mannitol. CONCLUSION: The dissociated
      effects of single doses of montelukast alone but not montelukast/desloratadine
      combination on AHR and recovery time, highlights the relative roles of histamine
      in initiating the bronchoconstrictor response and cysteinyl leukotrienes in
      sustaining it. Similar improvements in AHR and recovery time were observed
      following both indirect bronchoconstrictor stimuli.

PMID- 12801314
TI  - Bronchial responsiveness to adenosine-5'-monophosphate and methacholine as
      predictors for nasal symptoms due to newly introduced allergens. A follow-up
      study among laboratory animal workers and bakery apprentices.
AB  - BACKGROUND: In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine
      5'-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to
      methacholine. In this follow-up study we studied bronchial responsiveness to both
      stimuli as predictors of new-onset airway symptoms. METHODS: We included 118
      laboratory animal workers and bakery apprentices with a work experience of
      maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests
      (SPTs) to common and work allergens, blood eosinophil counting, and bronchial
      challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work
      allergens were repeated. Airway symptoms to common allergens and work allergens
      were defined as nasal symptoms, chest tightness or asthma attack during or after
      contact with either common or work allergen. Bronchial challenge tests were
      analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1), and by
      dose-response-slope (DRS). RESULTS: Fourteen subjects (12%) developed airway
      symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work
      allergens occurred in 64%, and was the strongest predictor of airway symptoms
      [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0-28.6]. Other predictors
      were airway symptoms to common allergens (RR 4.3, 95% CI 1.4-12.8), blood
      hypereosinophilia (RR 4.4, 95% CI 1.2-15.4) and BHR, with a slightly higher risk
      estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1-12.5 and RRmeth
      2.8, 95% CI 1.0-8.5). The difference was more distinct analysing airway
      responsiveness by DRS, for which AMP predicted symptoms better than methacholine
      (P < 0.05). CONCLUSIONS: Pre-existent bronchial inflammation or a preinflammatory
      state marked by AMP (hyper)responsiveness increases the vulnerability to develop
      nasal symptoms.

PMID- 12801315
TI  - Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen
      specific tumour necrosis factor alpha production and nuclear factor kappa B
      nuclear translocation in peripheral blood monocytes from atopic asthmatics.
AB  - BACKGROUND: The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful
      for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1
      antagonists on inhibition of inflammatory cytokine production is yet to be
      determined. OBJECTIVE: The present study was designed to determine the effect of
      pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by
      allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics.
      METHODS: PBM were obtained from normal control (n = 10) and Dermatophagoides
      farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured
      in the presence of Der f allergen. The production of TNF-alpha and nuclear
      translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic
      asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation
      by Der f. The additive effect of pranlukast and dexamethasone was also
      determined. RESULTS: PBM from atopic asthmatics cultured with Der f exhibited a
      significant increase in TNF-alpha production and nuclear translocation of NF
      kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and
      dexamethasone significantly inhibited production of TNF-alpha and nuclear
      translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive
      effect of pranlukast on low-dose dexamethasone was also demonstrated. However,
      LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation.
      CONCLUSION: Our results suggest that pranlukast may inhibit TNF-alpha production
      via suppression of NF-kappa B activation through pathways distinct from cysLTR1
      antagonism.

PMID- 12801316
TI  - Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T
      cells.
AB  - BACKGROUND: Pranlukast is a leukotriene 1 (LT1) receptor antagonist and is
      effective against bronchial asthma. Pranlukast inhibits contraction of the
      tracheal muscle, and thereby antagonizes the binding of LTC4, LTD4 and LTE4.
      However, the action of pranlukast on monocytes/macrophages and T cells is
      unknown. OBJECTIVE: We examined whether or not pranlukast inhibits TNF-alpha
      induced activation of nuclear transcription factor NF-kappa B, a factor that is
      essential for the expression of proinflammatory cytokines, on human monocytic
      1.3% dimethylsulphoxide (DMSO)-differentiated U-937 cells, which have cysteinyl
      LT1 (CysLT1) receptors on their membranes, and T cells (Jurkat), which do not.
      METHODS: We examined whether or not LTC4, LTD4 or LTE4 induced NF-kappa B
      activation in 1.3% DMSO-differentiated U-937 cells by Western blotting. The
      inhibitory effects of pranlukast and MK-571, which is an LTD4 receptor-selective
      antagonist, on TNF-alpha-induced NF-kappa B activation was evaluated by Western
      blotting and flow cytometry, and those on lipopolysaccharide (LPS)-induced
      interleukin-6 (IL-6) production in peripheral blood mononuclear cells (PBMC) were
      evaluated by enzyme-linked immunosorbent assaying. RESULTS: LTC4, LTD4 or LTE4
      did not induce NF-kappa B activation in 1.3% DMSO-differentiated U-937 cells.
      Western blotting demonstrated that 10-5 M pranlukast inhibits NF-kappa B
      activation in 1.3% DMSO-differentiated U-937 and Jurkat cells by about 40% & 30%,
      respectively. Flow cytometry demonstrated that pranlukast and MK-571 inhibit NF
      kappa B activation in 1.3% DMSO-differentiated U-937 and Jurkat cells in a dose
      related manner. Moreover, 10-5 M pranlukast and MK-571 inhibited LPS-induced IL-6
      production in PBMC by about 65% and 15%, respectively. CONCLUSION: Pranlukast and
      MK-571 partially inhibited NF-kappa B activation in 1.3% DMSO-differentiated U
      937 and Jurkat cells, and IL-6 release in PBMC. These findings are consistent
      with the idea that, independently of CysLT1 receptor antagonism, micromolar
      concentrations of pranlukast suppress the production of proinflammatory cytokines
      via inhibition of NF-kappa B activation in monocytes/macrophages and T cells, but
      the contribution of this effect to the anti-inflammatory activity of pranlukast
      at oral therapeutic doses in asthmatic patients is unclear.

PMID- 12801317
TI  - Inhibitory effects of interferon-gamma on the heterologous desensitization of
      beta-adrenoceptors by transforming growth factor-beta 1 in tracheal smooth
      muscle.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta 1) is generally considered
      to play an important role in the pathogenesis of chronic inflammation and
      fibrosis. OBJECTIVE AND METHODS: This study was designed to determine mechanisms
      of reduced responsiveness of guinea-pig tracheal smooth muscle to beta
      adrenoceptor agonists by TGF-beta 1, using isometric tension records and tissue
      cAMP measurement. Moreover, we examined the involvement of the signal
      transduction processes of TGF-beta superfamily in the desensitization of beta
      adrenoceptors. RESULTS: After exposure to 0.2-2000 pm TGF-beta 1 for 4-8 h, the
      inhibitory effects of 1 microm isoprenaline (ISO) and 10 microm forskolin on 1
      microm MCh-induced contraction were markedly reduced in a concentration-dependent
      fashion. The desensitization by TGF-beta 1 was greater against ISO than for
      forskolin. The values of EC75 for the curves for ISO after exposure to the normal
      bathing solution and TGF-beta 1 were 0.039 +/- 0.02 and 0.38 +/- 0.28 microm,
      respectively. The values of EC50 for the curves for forskolin under these
      conditions were 0.50 +/- 0.12 and 0.89 +/- 0.21 microm, respectively. On the
      other hand, the inhibitory effects of phosphodiesterase inhibitors such as
      theophylline and rolipram were not attenuated after exposure to TGF-beta 1.
      Concentration-inhibition curve for ISO was shifted to the right after exposure to
      2000 pm TGF-beta 1 for 8 h more than that curve for forskolin. In contrast, the
      curve for theophylline was not shifted to the right by TGF-beta 1. When the
      tissues were incubated with TGF-beta 1 in the presence of IFN-gamma, an
      intracellular antagonist of TGF-beta signalling, IFN-gamma inhibited the reduced
      response to ISO and forskolin after exposure to TGF-beta 1 in a concentration
      dependent fashion. After exposure to TGF-beta 1, the effects of cAMP accumulation
      of ISO was significantly reduced, however, neither forskolin-nor theophylline
      induced cAMP accumulation was affected. IFN-gamma had no significant effect on
      cAMP accumulation either to ISO or forskolin. CONCLUSIONS: Impairment of the beta
      adrenoceptors/adenylyl cyclase pathway are involved in heterologous
      desensitization of beta-adrenoceptors induced by TGF-beta 1 in airway smooth
      muscle. IFN-gamma functionally suppresses this phenomenon via cAMP-independent
      processes. Phosphodiesterase is still intact under this condition.

PMID- 12801318
TI  - Safety of nasal budesonide in the long-term treatment of children with perennial
      rhinitis.
AB  - BACKGROUND: Intranasal budesonide is an efficacious treatment for perennial
      allergic rhinitis. Long-term effects on safety, particularly in children, need
      further investigation. OBJECTIVE: To investigate the long-term safety of
      intranasal budesonide in children. METHODS: In an open trial, 78 children (5-15
      years) with perennial rhinitis were treated with intranasal budesonide
      pressurized metered dose inhaler 200 microg twice daily (delivered daily dose 256
      microg) for 12 months; 43 children stayed in the study for 12 additional months
      and were switched to aqueous suspension (400 microg delivered daily dose) for 6
      months. Statural growth, bone age, ophthalmologic and rhinoscopic status,
      cortisol and biochemical analyses in blood and urine were monitored during the
      first and second years, and adverse events (AEs) were continuously recorded.
      RESULTS: No significant effects on statural growth and bone age, compared with
      reference values, were observed. Morning plasma cortisol and 24-h urinary
      cortisol were not changed during treatment. Patients reported 195 AEs, most
      commonly nasal dryness (30%), blood-tinged secretions (21%) and, among non-nasal
      AEs, headache (13%). Rhinoscopy revealed no signs of mucosal atrophy, ulceration,
      or candidiasis but some nasal dryness. No treatment-related ophthalmological or
      biochemical aberrations were found. Reduction of blood eosinophils and nasal
      symptom scores, compared with pre-treatment values, indicated the efficacy of
      budesonide treatment. CONCLUSION: Long-term treatment for 1-2 years with
      intranasal budesonide 256-400 microg daily in children with perennial rhinitis
      revealed no negative effects on growth or endogenous cortisol production. Local
      side-effects were mild and patient symptoms decreased.

PMID- 12801319
TI  - Montelukast as an adjuvant to mainstay therapies in patients with seasonal
      allergic rhinitis.
AB  - BACKGROUND: Drug selection for optimal treatment of allergic rhinitis may be
      difficult and involve many diverse factors. OBJECTIVE: To evaluate montelukast,
      in the treatment of patients with seasonal allergic rhinitis, as an adjuvant to
      mainstay therapies, i.e., antihistamines and corticosteroids. METHODS: The study
      was a prospective, three-phased (per lasted 2 weeks) clinical trial. In phase I,
      patients were separated into two groups, based on the predominating symptoms: (1)
      runners (patients with moderate to severe sneezing/itchy, watery nose/itchy,
      watery eyes), and (2) blockers (patients with moderate to severe nasal
      congestion). The runners received antihistamine loratidine 10 mg daily, and the
      blockers received intranasal corticosteroid mometasone furoate 200 microg. In
      phase II, if patients were dissatisfied with the initial treatment, they were
      assigned to receive another study drug additionally. In phase III, for the
      patients unsatisfied with the treatment of loratidine plus mometasone furoate,
      montelukast 10 mg once daily was added. RESULTS: Of the 169 patients who entered
      phase I, 150 could be evaluated for treatment efficacy and safety. There were 108
      runners and 42 blockers. Physicians' and patients' assessments indicated that in
      phase I 58 runners (60.0% of 50 runners) and 36 blockers (33.3% of six blockers)
      were satisfied with their therapy. In phase II, 30 runners (27.7%) and two
      blockers (4.7%) were satisfied with the addition of other study drug. Totally
      62.6% of patients were satisfied at the end of phase I, and 84.0% at the end of
      phase II. Sixteen patients (66.6% of 24 patients) were satisfied with the
      addition of montelukast to the previous two drugs (in total, 10.6% of patients).
      Fourteen patients (12.2%) treated with loratadine, and three patients (0.3%)
      treated with mometasone, reported side-effect. CONCLUSION: The results of this
      trial indicate that 10% of patients with seasonal allergic rhinitis may be
      treated with the supplement of montelukast to mainstay therapy.

PMID- 12801320
TI  - Identification of Cucumisin (Cuc m 1), a subtilisin-like endopeptidase, as the
      major allergen of melon fruit.
AB  - BACKGROUND: Allergenic components in melon extracts have not been described in
      spite of the fact that melon (Cucumis melo) is a frequent allergy-eliciting
      fruit. The aim of this study was to evaluate allergenic components in melon
      extract and to report the identification of cucumisin as a major melon allergen.
      MATERIALS AND METHODS: Sera from 35 patients allergic to melon were selected on
      the basis of clinical symptoms, skin prick tests and oral challenge test.
      Allergenic components were detected by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis and immunoblotting. Molecular characterization of IgE-binding
      bands was performed by N-terminal amino acid sequencing. RESULTS: More than 10
      IgE-binding bands, between 10 and 80 kDa, were identified in melon extract. Out
      of them, four IgE-binding bands were major allergens: 14 kDa, 36 kDa, 54 kDa and
      67 kDa. These major allergens, except 14 kDa band, showed the same N-terminal
      sequence: T-T-R-S-W-D-F-L. Research conducted with protein databases identified
      this N-terminal sequence as cucumisin, an alkaline serine protease, which shares
      structural homology with microbial subtilisin. The molecular mass of the
      identified bands corresponds with different molecular forms of cucumisin produced
      during the processing or degradation of the enzyme: 67 kDa native cucumisin, 54
      kDa mature cucumisin and 36 kDa NH2-terminal cucumisin fragment. CONCLUSION:
      Cucumisin (Cuc m 1) and several N-terminal cucumisin fragments are the major
      allergens of melon. The ubiquitous distribution of this protein family (cucumisin
      like proteases) in many plant species and its high structural similarity suggest
      its potential role as a new panallergen in plant foods.

PMID- 12801321
TI  - Probing the mechanisms of low immunogenicity of a lipocalin allergen, Bos d 2, in
      a mouse model.
AB  - BACKGROUND: Bos d 2, a major bovine allergen of the lipocalin family, stimulates
      very weakly cow dust-asthmatic subjects' peripheral blood mononuclear cells and
      the spleen cells of several inbred mouse strains immunized with the allergen.
      OBJECTIVE: To identify the immune mechanisms accounting for the weak stimulatory
      capacity of Bos d 2. METHODS: The spleen cell responses of BALB/c mice immunized
      with the allergen and with hen egg lysozyme and tetanus toxoid as control
      antigens were examined using several in vitro methods. RESULTS: Analysis of the
      numbers of spleen cells in the antigen-stimulated in vitro cultures with the
      vital dye 7-amino-actinomycin D showed that Bos d 2 induced a smaller expansion
      of cells in comparison with the control antigens. Increased cell death in vitro
      did not account for the weak response against Bos d 2. The number of spleen cells
      reacting against Bos d 2 also proved to be the lowest when they were analysed by
      labelling the stimulated cells with 5-6-carboxyfluorescein diacetate succinimidyl
      ester or by enumerating cytokine-secreting cells by ELISPOT. Eliminating CD8+
      cells in the in vitro culture did not enhance the response against Bos d 2. Bos d
      2 was also the weakest of the antigens to stimulate the production of soluble
      cytokines. Adding IL-2, IL-4 or antibody against TGF-beta in the antigen
      stimulated spleen cell cultures enhanced the proliferative responses against all
      the antigens, whereas adding IL-12 or antibody against IL-4 or IL-10 did not
      enhance the responses. CONCLUSION: The results exclude several mechanisms of
      peripheral tolerance as an explanation for the poor immune response against Bos d
      2, and suggest that the allergen is recognized by a low number of specific T
      cells. The weak immunogenicity of Bos d 2 may be related to its allergenicity.

PMID- 12801322
TI  - Lipoteichoic acid from Staphylococcus aureus enhances allergen-specific
      immunoglobulin E production in mice.
AB  - BACKGROUND: Our previous study demonstrated that lipoteichoic acid (LTA) from
      Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling
      that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously
      with an allergen. However, the effects of LTA on allergen-specific IgE production
      in such sensitized mice have not been elucidated. OBJECTIVE: The purpose of this
      study was to determine the effects of LTA from S. aureus on allergen-specific IgE
      production in mice sensitized percutaneously with a house dust mite antigen (MA).
      METHODS: Mice were sensitized with a single topical application of MA and/or LTA
      to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE
      antibodies in sera from sensitized mice were detected by an enzyme-linked
      immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L
      molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph
      nodes of sensitized mice were analysed by flow-cytometry (FACS). RESULTS:
      Simultaneous sensitization with MA and LTA increased IgE production 3 weeks
      later, significantly more than sensitization with MA alone. FACS analysis of
      CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous
      sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen
      presenting cells such as B lymphocytes and dendritic cells more than
      sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes
      showed that simultaneous sensitization with MA and LTA increased the number of
      CD40L-expressing Th cells more than sensitization with MA alone. CONCLUSION:
      These results suggest that LTA enhances allergen-specific IgE production by a
      mechanism associated with up-regulation of CD40L-expressing Th cells and this
      might explain the role of skin colonization with S. aureus in AD patients.

PMID- 12801323
TI  - Comments regarding 'Marked improvement of the basophil activation test by
      detecting CD203c instead of CD63' by Boumiza et al.

PMID- 12801324
TI  - Cholecystectomy and duodenogastric reflux.

PMID- 12801325
TI  - Sentinel lymph node biopsy.

PMID- 12801326
TI  - Major trauma transfer in Western Australia.
AB  - BACKGROUND: The transfer of critically injured patients in a rural Australian
      setting presents a unique challenge to medical services due to the constraints of
      distance and time. The purpose of this study is to analyse which injuries are
      being transferred, how they occur, pretransfer intervention, transfer methods and
      transfer times. METHODS: The Trauma Registry Database collected data
      prospectively on all major rural trauma cases attending the Royal Perth Hospital
      between August 1994 and January 2000. Patients were divided into rural and
      metropolitan groups on the basis of trauma location, and the latter group used as
      a control. RESULTS: A total of 1275 major trauma patients were treated of which
      566 (44%) were from rural areas. Driver road traffic trauma was the most common
      cause of injury throughout, although most prominent in rural areas (30%vs 18%).
      For rural patients, the Royal Flying Doctor Service was responsible for 440 (79%)
      of transfers of which 83% had a doctor and a nurse escort. The most commonly
      transferred injuries from rural areas were head injury (63%) and thoracic injury
      (55%). A total of 450 (93%) rural patients were transferred to Royal Perth
      Hospital within 24 h of trauma although the mean transfer time was over 9 h.
      CONCLUSIONS: This data produces a realistic framework of how major trauma in
      rural areas is treated in Western Australia. It highlights some areas of good
      practice, such as transfer methods and escorts, but also highlights problem areas
      such as transfer times and pretransfer intervention.

PMID- 12801328
TI  - Outcomes of emergency common bile duct exploration: impact of preoperative
      endoscopic decompression.
AB  - BACKGROUND: Emergency common bile duct exploration (CBDE) is still required in
      patients acutely ill with complicated biliary tract stone disease when endoscopic
      decompression fails to reverse their condition. This study looks at the clinical
      profile of patients requiring emergency CBDE and examines the various factors
      influencing the postoperative outcome. METHODS: Clinical records of patients with
      emergency CBDE in Singapore General Hospital from January 1991 to December 1998
      were reviewed. Factors influencing postoperative outcomes, for example, pre
      existing medical problems, hepatic parameters, the impact of endoscopic
      procedures (if any) and indications for surgery, were correlated with
      postoperative morbidity and 30-day mortality. RESULTS: The records of 100
      patients were available for review. Major indications for emergency CBDE were
      cholangitis (51%) and intraoperative findings of common bile duct obstruction
      during emergency laparotomy (23%). Six patients had emergency CBDE because of
      iatrogenic complication of attempted therapeutic endoscopic retrograde
      cholangiopancreaticography (ERCP) for biliary stones. Overall mortality was 14.0%
      and 8.0% had retained stones. Mortality was significantly influenced by age,
      prior biliary disease, preoperative endoscopic biliary decompression in acute
      cholangitis (33.3%vs 9.4%, P = 0.035) and endoscopic complications. CONCLUSIONS:
      Among patients requiring emergency CBDE, uncomplicated preoperative endoscopic
      biliary decompression benefits patients with acute cholangitis.

PMID- 12801330
TI  - Surgical repair of spontaneous renal allograft rupture: a new procedure.
AB  - BACKGROUND: The purpose of the present paper is to introduce a new surgical
      procedure using the external oblique aponeurosis (EOA) for repair of spontaneous
      renal allograft rupture. METHODS: Thirty-eight cases with spontaneous renal
      allograft rupture were encountered in 1000 consecutive kidney transplants between
      April 1991 and August 2000. Thirty-three cases underwent surgical exploration
      with two grafts undergoing nephrectomy, while a further 31 were repaired using
      the new surgical procedure. The external oblique aponeurosis (EOA) from the
      incision was trimmed into 1 cm x 1 cm square pieces. A 2/0 Dexon suture was
      placed through each piece of the EOA, then through the parenchyma of the kidney
      perpendicular to the rupture. Each suture was then placed through another piece
      of EOA and tied. RESULTS: Two repaired grafts were removed on day 7 and day 10,
      one due to graft re-rupture and another with ischaemia secondary to irreversible
      acute rejection. The graft function of 29 cases had recovered completely at 30
      days following surgical repair with one graft improving rapidly. Thirteen grafts
      were diagnosed as undergoing mild to moderate acute rejection, whereas a further
      20 cases were considered to have acute tubular necrosis on histopathology. The
      allograft survival rate at 1 year and 5 years post grafting was 86% and 64%,
      respectively. No patients died from postoperative complications following repair
      using this procedure. CONCLUSIONS: Spontaneous renal allograft rupture is a
      relatively common post-transplant complication secondary to either acute tubular
      necrosis or acute rejection. This new surgical procedure is proposed as a
      reliable and practical method of repair following graft rupture. Preservation of
      graft function and viability following rupture appears achievable both in the
      medium and long-term.

PMID- 12801331
TI  - Thrombotic complications of venous aneurysms.
AB  - BACKGROUND: Venous aneurysms are rare vascular anomalies that have been reported
      to occur throughout the body. We report a unique variation, namely a thrombosed
      subclavian vein aneurysm. METHODS: A review of the records of patients with
      documented venous aneurysms presenting to the St George Hospital and their
      associated imaging was made. A literature search for articles pertaining to
      venous aneurysms was performed. RESULTS: Four cases of venous aneurysms were
      identified; one subclavian vein, one inferior vena cava and two popliteal. The
      clinical course of these cases is detailed, along with a review of the
      literature. CONCLUSIONS: Venous aneurysms are infrequent findings and indicate
      that the patient is at significant risk of thrombosis. Popliteal vein aneurysms
      should be treated surgically.

PMID- 12801332
TI  - Outcome after intramedullary nailing of femoral shaft fractures.
AB  - BACKGROUND: The results of intramedullary nailing of femoral shaft fractures from
      Australian institutions have not been widely reported. This study examines a
      consecutive group of patients treated at a major metropolitan trauma centre and
      reports on the injury statistics and outcome data, and compares this to
      previously reported results from the literature. METHODS: A total of 101
      fractures in 97 consecutive adult patients were included in the study. Nine
      patients were excluded. At a minimum of 6 months post injury, 54 patients were
      interviewed by telephone and 35 patients presented for clinical review and
      underwent physical examination, computed tomography (CT) scanogram of the lower
      limbs and Short Form 36 questionnaires. RESULTS: Road trauma accounted for 81% of
      injuries and 15% of fractures were open. Of the 54 patients reviewed, 13 (23%)
      required further surgery for delayed or non-union. Of the 35 who presented for
      physical examination, there was poor correlation between perceived leg length
      discrepancy and measured leg length discrepancy on examination or scanogram.
      Presence of a limp correlated with measured leg length discrepancy of more than 1
      cm but did not correlate with rotational abnormality measured on CT scanogram.
      Pain at the hip, thigh or knee was present in 60% of patients. The Short Form 36
      scores for physical functioning, role--physical, bodily pain, general health and
      vitality were all significantly lower than population norms with P values ranging
      from <0.001-0.05. Subgroup analysis comparing isolated femur fracture to multi
      trauma patients for all five of these parameters revealed significant differences
      only in the multi-trauma group. CONCLUSION: The incidence of pain, limp, leg
      length discrepancy and delayed or non-union is higher in this study than in
      previously reported results of intramedullary nailing for femoral shaft
      fractures. This may be due to differences in the patient population, the skill
      level of the operating surgeon, or incomplete follow up.

PMID- 12801333
TI  - Single stage primary anastomosis without colonic lavage for left-sided colonic
      obstruction due to acute sigmoid volvulus: a prospective study of one hundred and
      ninety-seven cases.
AB  - BACKGROUND: The purpose of this study was to examine the feasibility of single
      stage resection and anastomosis for acute left-sided colonic obstruction due to
      acute sigmoid volvulus without intraoperative lavage. Mechanical bowel
      preparation has been shown to be unnecessary for elective colorectal surgery.
      Colonic decompression without intraoperative lavage may simplify operations in
      acute left-sided colorectal obstruction. METHODS: Emergency resection of acute
      sigmoid volvulus was performed. This was followed by primary anastomosis without
      on-table lavage after closed bowel decompression. RESULTS: A total of 197
      patients underwent bowel decompression, resection and primary colonic
      anastomosis. Two patients developed anastomosis leak, requiring re-laparotomy,
      Hartmann's procedure and delayed closure. Two deaths occurred postoperatively;
      these were unrelated to the nature of the surgery. The mean hospital stay was 9.8
      days. CONCLUSION: Primary colonic anastomosis can be safely done for obstructed
      left colon due to acute sigmoid volvulus without intraoperative colonic lavage.

PMID- 12801335
TI  - Epidemiology of abdominal aortic aneurysm in an Asian population.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are common in the Caucasian
      population. Apart from reported differences in the occurrence of AAA in the black
      and white populations, there are few studies on the incidence of AAA in the Asian
      population. METHODS: A prospective database of all patients with AAA seen between
      1996 and 1999, in the South-East Asian state of Sarawak in Borneo Island, was
      analysed. The demographic data included patient's age, sex, ethnic group, date of
      diagnosis, comorbidities, presentations and treatment outcomes. These were
      compared with the state population's demographic statistics. RESULTS: Diagnoses
      of AAA were made in 123 patients during the study period. The male to female
      ratio was 3.5 : 1. The age range was 39-88 years with a median age of 70 years.
      Four patients were younger than 55 years. The incidence rate for the at-risk male
      population older than 50 years was 25.6/100,000. The incidence rate reached
      78.3/100,000 for males older than 70 years. The incidence rate for females older
      than 50 years was 7.6/100,000 and for those older than 70 years it was
      18.7/100,000. All races were affected. Smoking, hypertension or respiratory
      disorders were present in more than 40% of the patients. Half of the patients
      underwent surgical repair. CONCLUSION: This study shows that AAA in this Asian
      population is not uncommon and the incidence is comparable to the Western world.

PMID- 12801336
TI  - Nasal fractures: a study comparing local and general anaesthesia techniques.
AB  - BACKGROUND: The objective of the present study was to examine the outcome of
      nasal fracture reduction under both local anaesthesia and general anaesthesia
      techniques. METHODS: Patient records were obtained from clinic lists of patients
      attending the otolaryngology (ORL) outpatient unit at Wellington Hospital or the
      plastic surgical unit at Hutt Hospital over a 24-month period. To meet criteria
      for inclusion, patients had to have an isolated nasal deformity, be aged 14 years
      or older and be at least 6 months post reduction. Functional and aesthetic
      results were assessed using subjective and objective end outcome measures. A
      questionnaire was developed and used to assess subjective outcomes. The number of
      patients proceeding to open operative correction was used for the objective
      measure, which included septoplasty, septorhinoplasty or rhinoplasty. RESULTS: A
      total of 197 patients had nasal fractures manipulated over this period. One
      hundred and seven were manipulated under general anaesthesia (GA) and 90 were
      manipulated under local anaesthesia (LA). The questionnaire completion rate was
      66%. Patient demographics were statistically similar between the two groups.
      There was no statistical difference in patients" subjective assessment of outcome
      with treatment by GA or LA. More patients preferred to have their fracture
      manipulated under GA but this was not statistically significant. There was no
      significant difference between GA and LA groups in progression to open operative
      correction. CONCLUSIONS: Both LA and GA appear to be acceptable and satisfactory
      methods of anaesthesia in the reduction of simple displaced nasal fracture.

PMID- 12801337
TI  - Duodenogastric reflux after biliary surgery: scintigraphic quantification and
      improvement with erythromycin.
AB  - BACKGROUND: Persistence of dyspeptic symptoms after cholecystectomy or
      choledochoduodenostomy is common. There is -evidence that at least some of these
      symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study
      was to quantify DGR before and after cholecystectomy, with or without
      choledochoduodenostomy, and endoscopic sphincterotomy for common bile duct
      stones, and to assess the effect of erythromycin on the increased DGR. METHODS:
      Forty-seven patients before and after cholecystectomy, 26 after cholecystectomy
      and choledochoduodenostomy and nine after sphincterotomy had postprandial (300 mL
      of fresh milk, 4% fat) duodenogastric reflux measured by 99mTc-hepatic imino
      diacetic acid scintigraphy. Patients with a DGR index (DGRi) >20% were considered
      as having pathological DGR that justifies symptoms, and their DGRi was reassessed
      after administration of 200 mg of erythromycin intravenously. RESULTS: Twenty
      seven patients before cholecystectomy (57%) showed a normal DGRi <7%. In five
      cases DGRi was greater than 20%. After cholecystectomy, duodenogastric refluxes
      increased, so that only 16 patients (32%) showed a normal DGRi, while a DGRi >20%
      was observed in 10 cases. Only eight patients after cholecystectomy and
      choledochoduodenostomy (23%) presented with a DGRi within the normal range. The
      remaining 18 had a DGRi >7%. Five of them exhibited a DGRi >20%. Of the nine
      patients with sphincterotomy, three showed a DGRi >20%. Erythromycin almost
      completely normalized DGRi in all 18 patients with pathological DGR (P < 0.0001).
      CONCLUSIONS: Duodenogastric reflux is common after biliary surgery, including
      endoscopic sphincterotomy. Erythromycin appears to decrease duodenogastric reflux
      to normal levels.

PMID- 12801338
TI  - Impact of core biopsy on the management of screen-detected ductal carcinoma in
      situ of the breast.
AB  - BACKGROUND: Screen-detected ductal carcinoma in situ (DCIS) usually presents as
      clinically impalpable microcalcification. Although core biopsy is well
      established as a diagnostic modality for invasive breast cancers, few reports
      address its impact on the management of screen-detected DCIS. We examined the
      sensitivity of core biopsy in diagnosing screen-detected DCIS, as well as its
      role in facilitating one-step surgery in the community, especially a breast
      conserving approach. METHODS: Through the Monash BreastScreen database, we
      reviewed the management of 148 patients diagnosed with pure DCIS over a 4-year
      period. Particular attention was paid to the sensitivity and surgical margin
      status of 63 patients who underwent initial assessment with core biopsy, compared
      to patients who underwent excisional biopsy or fine needle aspiration cytology
      (FNAC). RESULTS: Core specimens in 63 patients yielded positive histology in 57
      (90%), allowing for breast-conserving surgery in 45 and mastectomy in 12.
      Negative margins were obtained in 73% of those treated by breast-conserving
      surgery, compared to 51% negative margins among those who underwent excisional
      biopsy initially. Overall, 45 of 57 patients with a positive core biopsy
      histology (79%) underwent one-step surgery. Those assessed by FNAC had a 48%
      incidence of non-diagnostic/benign cytology. CONCLUSIONS: Core biopsy facilitates
      one-step surgery for screen-detected DCIS, and potentially reduces the number of
      surgical procedures. Stereotactic core biopsy for suspicious microcalcifications
      should replace hookwire-guided excisional biopsy and FNAC as the diagnostic
      modality of choice.

PMID- 12801339
TI  - Anatomical justification of Belghiti's 'liver hanging manoeuvre' in right
      hepatectomy with anterior approach.
AB  - BACKGROUND: In cases of right hepatectomy for huge tumour encroaching onto the
      diaphragm, the 'anterior approach' is the most common surgical procedure
      undertaken. The 'liver hanging manoeuvre' has been described previously as an
      adjunct to this procedure. It involves the dissection of a retrohepatic avascular
      plane anterior to the surface of the inferior vena cava. A tape is then passed
      through and the liver is resected under suspension. METHODS: Cadaveric specimens
      were used to identify the structural relationship of the avascular plane and also
      to determine whether it is truly avascular. RESULTS: Thirteen cases were
      analysed. The mean length of the avascular tunnel was 6.4 +/- 1.0 cm. The median
      number of accessory hepatic veins within the tunnel was two (zero to three). At
      the caudal half of the tunnel, the median number of veins was two (zero to
      three). As for the cranial half of the tunnel, there were two cases with one vein
      in each. CONCLUSIONS: The key to the liver hanging manoeuvre is to develop the
      retrohepatic tunnel. However, our study showed that it is not absolutely
      avascular. During the blind dissection, there is a chance of damaging a
      retrohepatic vein. This may result in troublesome haemorrhage within the confines
      of the tunnel. Video-assisted dissection of this region may help in
      visualisation, and hence control, in order to avoid bleeding.

PMID- 12801340
TI  - Solid pseudopapillary tumour of the pancreas.
AB  - BACKGROUND: Solid pseudopapillary tumour of the pancreas is a rare pancreatic
      tumour that occurs predominantly in women, with very few cases reported in men.
      This is a tumour with low malignancy potential and surgical resection usually
      results in cure. METHODS: A retrospective review of our experience with solid
      pseudopapillary tumours between April 1992 and December 2000 was undertaken.
      RESULTS: Six patients were identified including one male patient. The median age
      was 30 years, with four patients presenting with abdominal pain and discomfort
      and two patients presenting with palpable abdominal masses. The mean tumour
      diameter was 10.2 cm and the lesions were found mainly in the body and tail of
      the pancreas. Only one patient had tumour at the pancreatic head. One patient had
      a locally invasive disease and another had peritoneal spread. None of the
      patients received adjuvant therapy. The mean follow up was 3.8 years (range: 1.5
      10.0) and all patients were free of recurrence to date. CONCLUSION: SPT is a rare
      tumour with an unclear origin that has a distinct histology and presentation.
      Although preoperative diagnosis is difficult by computed tomography, magnetic
      resonance imaging may potentially improve this situation. In general, this is a
      tumour of very low malignant potential and long-term survival is excellent after
      resection of the tumour.

PMID- 12801342
TI  - Effects of heterotopic bone formation on outcome after hip arthroplasty.
AB  - BACKGROUND: Heterotopic bone formation (HBF) is well established as a frequent
      complication of major hip surgery, but its importance as a cause of impaired
      postoperative outcome is uncertain. METHODS: A systematic overview of all studies
      that reported the association of HBF with the risk of impaired range of movement,
      pain or poor function, late after hip arthroplasty. RESULTS: A computer-based
      search identified 37 relevant studies that included 10,826 individuals. There
      were 30 studies (8305 participants) that assessed the association between HBF and
      range of movement, 14 studies (7420 participants) that assessed the association
      between HBF and pain and 16 studies (5918 participants) that assessed the
      association between HBF and function. Overall, there was a clear positive
      association of HBF with the risk of an impaired range of movement at the hip
      joint and with the risk of a poor functional outcome. The association of HBF with
      pain was unclear. There was evidence of effects of mild-to-moderate HBF on the
      postoperative range of movement. CONCLUSIONS: These results suggest that mild-to
      moderate HBF, not just severe HBF, can influence outcome after major hip surgery.
      HBF may therefore be a more frequent cause of postoperative symptomatology than
      is generally believed. It is possible that effective prophylactic regimens will
      improve outcomes in large numbers of patients.

PMID- 12801341
TI  - Single institution's initial experience with sentinel lymph node biopsy in breast
      cancer patients.
AB  - BACKGROUND: The sentinel lymph node is the first draining node from a cancer
      bearing area and is therefore the first to manifest metastasis. In breast cancer
      it has been shown to predict the axillary status. Axillary dissection provides
      information determining prognosis and need for adjuvant therapy but carries a
      certain morbidity. Our aim was to determine the feasibility of detecting the
      sentinel node in a teaching hospital and whether the sentinel node accurately
      predicts the axillary status. METHODS: All patients with stage I and II breast
      cancer and non-palpable axillary nodes were eligible, including those with
      previous excision biopsy. We excluded pregnant women, those with previous
      axillary surgery and women with advanced breast cancer with enlarged axillary
      nodes. The sentinel node was detected with technetium-99m-labelled tin colloid
      and vital blue dye and removed, and axillary clearance was performed. RESULTS: A
      total of 312 patients were examined from August 1996 to December 1998. The mean
      age was 53 years (range 28-83) and mean tumour size 2.6 cm (range 0.2-9.0). The
      detection rate of the sentinel node was 86%. The sentinel lymph node predicted
      the axillary status with a sensitivity of 83% and specificity of 100%. The false
      negative rate was 16.7%. CONCLUSIONS: Detection of the sentinel lymph node is
      feasible and it can accurately predict the nodal status of the axilla. However,
      the high false-negative rate precludes as yet the use of sentinel lymph node
      biopsy in replacing axillary clearance as the standard of care for breast cancer.

PMID- 12801343
TI  - An economic perspective on evidence-based patient choice in surgery.
AB  - The aim of the present paper is to provide an economic perspective on current and
      emerging issues relating to surgical decision-making. The central issue discussed
      in the paper is choice and how this relates to patient management. The paper
      explores three factors that may influence the nature of choice; they are-
      evidence-based medicine, patient involvement in making choices and the role of
      cost-effectiveness analysis in surgery. Together, these factors are driving a
      shift from the traditional model of care based on medical beneficence to one
      based more on individual patient autonomy. This shift has been described as a
      move towards 'evidence-based patient choice' (EBPC). The concept of EBPC is
      relatively new and ill defined. Yet it encapsulates what is happening now and
      what will occur more dramatically in the future; that is, the nature of the
      relationship between surgeon and patient is changing. We hope that this paper
      will provoke discussion on the concept of EBPC and cost-effectiveness analysis in
      surgical decision-making.

PMID- 12801344
TI  - Sir Thomas Browne: physician 1605-1682 and the Religio Medici.
AB  - Sir Thomas Browne, 1605-1682, a physician of great scholarship, published his
      Religio Medici in 1642 as an expression of his own religious and professional
      beliefs. He had studied in Oxford and then turned to medicine and he pursued
      these studies in the Uni-versities of Montpellier, Padua and Leiden in Europe.
      Returning to Britain, he completed his medical degree and practised in Norwich
      for over three decades. He was considered one of the foremost physicians in
      England, although he did not practise in London, and he was conscious of the need
      for doctors to have a good knowledge of anatomy at a time when, before
      anaesthesia, surgery was becoming more adventurous. He was knighted by King
      Charles II in 1671. The curtailment of anatomy teaching in many undergraduate and
      postgraduate schools of medicine today would not have appealed to Browne. It is
      of growing concern to surgical colleges and academies who are now required to
      provide additional postgraduate anatomy teaching in order to satisfy the
      requirements of their examinations for surgeons.

PMID- 12801345
TI  - Writings of Daniel Turner and his views on the practice of surgery.
AB  - In the Cowlishaw collection there are two publications by Daniel Turner (1667
      1740). These are his Apologia Chyrurgica and an epistle to Dr James Jurin. Turner
      qualified first as a surgeon and later practised as a physician. He was a
      successful author and it has been said that 'His cases are not stated in the most
      delicate terms, nor was politeness among his excellencies'. Both of these
      publications were very critical of the various pretenders who engaged in medical
      practice at that time. A review of these works has been carried out and
      consideration of the type of practice in which these people were engaged.

PMID- 12801346
TI  - Sir Colin MacKenzie: a remarkable legacy!

PMID- 12801347
TI  - Sir William Turner and his studies on the mammalian placenta.
AB  - William Turner was appointed Professor of Anatomy at the University of Edinburgh
      in 1867, and from 1903 until his death in 1916, he was Principal and Vice
      Chancellor. He was an outstanding teacher and many of those he taught went on to
      occupy chairs of anatomy. He published widely on anatomical subjects and one of
      his interests was comparative anatomy and physiology of the placenta. This paper
      takes a brief look at Turner's studies on the anatomical structure of the
      placenta, its comparative anatomy, his thoughts about its physiology and its
      place in the evolutionary process. At the time, these lectures constituted an
      anatomical and physiological classic. At the time Turner prepared his lectures,
      which were delivered in 1875 and 1876, little was known about the gestatory
      process in marsupials or monotremes. These mammals have a very brief period of
      intrauterine gestation and placentation and mention is made of studies that have
      been done in recent times on this subject.

PMID- 12801348
TI  - Foundation lecture. Fracture care of friend and foe during World War I.
AB  - BACKGROUND: In the early years of trench warfare, compound lower limb fractures
      caused by gunshot missiles prompted the -questioning of traditional splintage
      techniques and established evacuation methods. These prejudiced recovery and
      delayed surgery, often by many days, causing a high mortality rate especially for
      open femoral fractures. Importantly, battle weaponry was modified by differences
      in climate and terrain in Mesopotamia, Gallipoli, the Alps and the Northern
      European plain, to manifest differences in wound pathology. In Flanders, the
      static situation limited simple bullet wounds and launched a high percentage of
      jagged shell -fragment injuries complicated by tissue destruction, in-driven
      clothing and metal contaminated with mud, lethal bacteria and spores. From no
      mans-land, soldiers with arm fractures scrambled back unaided, with tibial
      fractures they might hobble between two comrades, but with femoral fractures they
      were helpless unless stretcher bearers arrived. Often they did not, or only after
      a lull in fighting, by which time death from blood loss or exposure supervened.
      Even on a stretcher, poor fracture immobilization and long arduous carries added
      to shock and mortality. Remedies to these deficiencies and observations by
      Australasian, Austrian, British, Canadian, French, German, South African and
      American surgeons are noted. CONCLUSIONS: Trained to treat bullet wounds in open
      terrain, many military medical organizations were slow to adjust to the novel
      challenges associated with trench warfare. However, from 1917 well-trained
      stretcher bearers, efficient application of the Thomas splint, better control of
      haemorrhage and more rapid evacuation with motorized ambulances reduced deaths,
      amputation rates and long-term disability significantly.

PMID- 12801349
TI  - Incomplete excision of basal cell carcinoma.

PMID- 12801350
TI  - Abdominal apoplexy: a potentially fatal enigma.

PMID- 12801351
TI  - Successful conservative management of neutropenic enterocolitis: a report of two
      cases and review of the literature.

PMID- 12801352
TI  - Kimura's disease: upper limb involvement in a Pacific Island man.

PMID- 12801355
TI  - What is the significance of an isolated positive cryptococcal antigen in the
      cerebrospinal fluid of cancer patients?
AB  - We evaluated the significance of an isolated positive cryptococcal antigen titer
      in the cerebrospinal fluid (CSF) of 12 cancer patients. In most of the cases, the
      test had a low titer, was frequently associated with an intracranial malignancy
      and was considered to represent a false-positive result. Hence, an isolated
      cryptococcal antigen in the CSF has an unclear clinical value and must be
      interpreted with caution.

PMID- 12801356
TI  - Antifungal susceptibility of clinical and environmental isolates of Cryptococcus
      neoformans to four antifungal drugs determined by two techniques.
AB  - A total of 64 Cryptococcus neoformans strains, including clinical and
      environmental Brazilian isolates var. neoformans and var. gattii, were tested for
      susceptibility to amphotericin B, 5-flucytosine, fluconazole and itraconazole.
      The tests were performed according to the recommendations of National Committee
      of Clinical Laboratory Standards and the method of macrodilution in liquid medium
      of Shadomy et al. [Manual de Microbiologia Clinica, 4th ed. Buenos Aires:
      Editorial Medica Panamericana, 1987: 1229-38]. For most drugs there was a
      significant difference between the readings taken at 24 and 48 h with both
      methods. When the minimum inhibitory concentrations obtained by the two
      techniques were compared, significant differences were observed for amphotericin
      B and fluconazole. Overall, differences in drug susceptibility with respect to
      the origin of the isolates or the variety of the fungus were not observed. As an
      exception, the gattii variety exhibited a high resistance rate to amphotericin B
      when the technique of Shadomy et al. was applied, a fact possibly related to the
      greater difficulty for treatment of the disease caused by this fungal variety.

PMID- 12801357
TI  - Enzymuria following amphotericin B application in the rat.
AB  - The effect of amphotericin B application on urinary renal tubule enzyme excretion
      was investigated in rats treated with amphotericin B (1.5 mg kg-1 b.i.d., i.v.)
      for 4 days. Application of amphotericin B induced a significant higher daily
      urinary enzyme activity of the renal tubular enzymes N-acetyl-beta
      glucosaminidase (NAG), beta-glucuronidase (GRS), alanine-aminopeptidase (AAP) and
      gamma-glutamyltransferase (GGT) in comparison with controls and sodium
      deoxycholate treated animals as well. A significant increase in the renal
      excretion of NAG, GRS, AAP and GGT occurred after the first day of amphotericin B
      treatment and continued until the fourth day. Following treatment for 4 days with
      amphotericin B urine AAP activity amounted to 69 +/- 19 U g-1 creatinine,
      control: 39 +/- 7 U g-1 creatinine (P < 0.05). After 4 days GGT excretion
      increased to 803 +/- 238 U g-1 creatinine, control: 445 +/- 106 U g-1 creatinine
      (P < 0.05). At the fourth day NAG excretion was 80 +/- 39 U g-1 creatinine,
      control: 23 +/- 5 U g-1 creatinine (P < 0.05) and GRS 724 +/- 604 U g-1
      creatinine (amphotericin B), control: 276 +/- 158 U g-1 creatinine (P < 0.05).
      Treatment with amphotericin B decreased the creatinine clearance significantly:
      0.94 +/- 0.16 ml-1 min-1 vs. control 1.35 +/- 0.29 ml-1min-1 (P < 0.05).
      Fractional sodium and potassium excretion was not influenced by amphotericin B.
      The application of sodium deoxycholate had no influence on urinary renal tubular
      enzyme activity. The results show that amphotericin B application induces early
      enzymuria of renal tubule enzymes suggesting damage of proximal renal tubules.

PMID- 12801358
TI  - Disseminated aspergillosis due to Aspergillus flavus in an experimental model:
      efficacy of azole therapy.
AB  - The aim of this investigation was to create a reproducible experimental model of
      disseminated Aspergillus flavus aspergillosis, and to compare the relative
      therapeutic efficacies of itraconazole and fluconazole in this model. Temporarily
      immunosuppressed male Wistar rats received intravenous challenge by A. flavus
      conidia. Treatment was initiated 24 h later with oral itraconazole (1 mg kg-1 BW
      day-1), oral fluconazole (1 mg kg-1 BW day-1) or excipient only (infected
      untreated rats); this was continued for 10 days. At this time, although 100%
      mortality had occurred among all infected-untreated rats, no mortality was noted
      among the control-uninfected, infected-itraconazole-treated or infected
      fluconazole-treated rats. After killing, essential organs were processed for
      microbiological and histopathological studies. Aspergillus flavus was recovered
      in high colony counts from the organs of infected-untreated rats (lungs > liver >
      brain > kidneys), but in significantly lower colony counts, or not at all, from
      the organs of itraconazole-treated and fluconazole-treated rats.
      Histopathological alterations were pronounced in tissues of infected-untreated
      rats, but less so in treated rats. These data suggest that administration of
      itraconazole or fluconazole sufficiently early may prevent, or retard,
      progression of lesions in disseminated aspergillosis.

PMID- 12801359
TI  - Fluconazole toxicity is independent of oxidative stress and apoptotic effector
      mechanisms in Saccharomyces cerevisiae.
AB  - Fluconazole toxicity was previously shown to require intact mitochondria in
      Saccharomyces cerevisiae, however, the mechanism of mitochondrial-dependent azole
      toxicity is unclear. Here we show that fluconazole toxicity is not attenuated by
      the overexpression of the mitochondrially-acting human antiapoptotic protein Bcl
      2 nor is it increased by the presence of the oxidating agents in S. cerevisiae.
      Our data further support the notion that mitochondrial toxicity in the presence
      of azoles is modulated by the conversion of ergosterol precursors to toxic
      sterols.

PMID- 12801360
TI  - Oral candidosis in patients with removable dentures.
AB  - The prevalence of Candida species with and without denture-related stomatitis
      were evaluated in 167 Jordanian patients. The study revealed that 47 (28%) of the
      patients with denture-related stomatitis were colonized with Candida species
      (clinical group). Candida albicans was responsible for most cases of denture
      related stomatitis (72%), and it was the only species capable of secreting
      aspartic proteinases. The study also indicated that candidal colonization was not
      influenced by predisposing haematological deficiencies, as both the clinical and
      control patient groups showed comparable haematological parameters and the
      differences were not significant (P > 0.05). All Candida species isolates were
      100% susceptible to amphotericin B, while these isolates were less susceptible
      (25-75%) to fluconazole.

PMID- 12801361
TI  - Use of Punica granatum as an antifungal agent against candidosis associated with
      denture stomatitis.
AB  - The aim of this study was to evaluate the use of a gel containing the extract of
      Punica granatum as an antifungal agent against candidosis associated with denture
      stomatitis. Sixty patients with denture stomatitis confirmed by clinical and
      mycologic examination were selected. The patients were randomly allocated in two
      groups of 30 individuals each according to the medication prescribed: group A
      used miconazole (Daktarin(R) gel oral) and group B used a gel of P. granatum
      Linne (pomegranate). Both groups used the medicines three times per day for 15
      days. Forty-eight hours after finishing the treatment the patients were re
      examined and a second set of samples was collected for mycologic examination. The
      medicines were evaluated for their clinical response and negativity for Candida.
      The clinical results showed a satisfactory and regular response in 27 and 21
      subjects of groups A and B, respectively. Negativity of yeasts was observed in 25
      subjects of group A and 23 of group B. It can be concluded that the extract of P.
      granatum may be used as a topical antifungal agent for the treatment of
      candidosis associated with denture stomatitis.

PMID- 12801362
TI  - Sialic acids are absent from the dermatophytes Trichophyton mentagrophytes and
      Trichophyton rubrum.
AB  - Experiments were performed to determine whether sialic acids are expressed in two
      dermatophytes: Trichophyton rubrum and T. mentagrophytes, similarly to other
      fungal pathogens. Chemical extraction of mycelia and microconidia followed by
      high-performance thin-layer chromatography and colorimetric assays were all
      negative for sialic acid. Incubation of dermatophytes in the presence of Limax
      flavus agglutinin, specific for sialic acid, was negative in a fluorescence
      staining test. We have also used other lectins that bind to sialic acid and/or
      other sugar residues, and these ligands coupled to fluorescein strongly stained
      these fungi. Such fluorescence staining was not abolished or reduced when fungi
      were pretreated with sialidase. Different strains of influenza virus which
      recognize sialic acid residues were also used, but no agglutination of the
      dermatophytes was observed. Based on these methods, which successfully revealed
      the presence of sialic acids in other fungal pathogens, we show that these
      monosaccharides do not occur in both dermatophyte species. Thus, sialic acids do
      not seem to play a role in the pathogenicity of these fungi.

PMID- 12801363
TI  - The maintenance and preservation of keratinophilic fungi and related
      dermatophytes.
AB  - A total of 239 fungi belonging to nine genera and 23 species were maintained on
      agar slopes in a refrigerator at +8 +/- 1 degrees C and in sterile distilled
      water, under liquid paraffin, dried on silica gel, in sterile soil at room
      temperature. A limited number has been stored by freeze-drying between 1985 and
      1998. It is recommended that each isolate should be maintained by at least two of
      these methods. The choice of the method will depend to a large extent on the
      equipment and facilities available in the laboratory. It is reported that simple
      methods can be used for preservation of keratinophilic fungi and related
      dermatophytes.

PMID- 12801364
TI  - An epidemiological and clinical study of untreated patients with tinea pedis
      within a company in Japan.
AB  - In this study, we investigated epidemiological and clinical aspects of
      dermatophyte foot infections among employees of one dairy product company located
      in Kanagawa prefecture in central Japan. Sixty-nine of 377 subjects were reported
      having "athlete's foot" in response to a simple questionnaire. A subsequent
      mycological examination revealed 41 untreated patients with tinea pedis and/or
      tinea unguium (89% of subjects examined) and the overall prevalence was estimated
      at 18%. Comparing severity scores of five clinical symptoms (itching, erythema,
      vesicles/pustules, erosion/maceration, and scales) between those untreated
      patients within the subjects and another group of patients who spontaneously
      attended dermatological clinics to treat tinea pedis, itching, erythema, and
      total score were significantly higher in the latter group.

PMID- 12801365
TI  - Dermatomycoses in the Rijeka area, Croatia, before, during and after the war 1990
      1999.
AB  - The frequency of dermatomycoses as well as the spectrum of causative agents in
      the Rijeka area, northwestern part of Croatia, in the periods before and during
      the war (1990-1994) and in the postwar period (1995-1999) were analyzed. A total
      of 20 463 patients with clinically suspected dermatomycoses referred to the
      Department of Dermatovenerology, Clinical Hospital Center Rijeka, was examined.
      In the period from 1990 till 1994, 2462 samples were positive, compared with 2250
      positive samples during the period from 1995 to 1999. The most frequently
      isolated dermatophytes were in both periods Trichophyton mentagrophytes and
      Microsporum canis, followed by Microsporum gypseum, Epidermophyton floccosum,
      Trichophyton verrucosum and in the first period T. rubrum. An intensive change in
      composition of the flora was observed in the postwar period, mainly connected to
      the migration of population from other regions to the Rijeka area. This was
      demonstrated by a disappearance of T. verrucosum and T. rubrum and by an eruptive
      occurrence of Trichophyton violaceum. This antropophilic species became third
      representative in the postwar period, followed by M. gypseum, and E. floccosum.
      Our data were compared with those obtained in the same area in previous studies,
      and with results obtained in other countries.

PMID- 12801366
TI  - Prevalence of tinea capitis in primary schools in Turkey.
AB  - The aim of our study was to determine the prevalence of tinea capitis in Middle
      Anatolia. Between February 2000 and April 2000, a school survey of 4760 primary
      school children was carried out and 34 cases of tinea capitis were clinically
      diagnosed. Sixteen (0.3%) of them were diagnosed both clinically and using
      culture. Eighteen cases (52.9%) were diagnosed microscopically whereas the
      remaining 16 cases (47.0%) had a clinical diagnose. We also isolated and
      identified the following species of fungi causing the infection: Trichophyton
      verrucosum (five cases), T. rubrum (three), T. mentagrophytes var. mentagrophytes
      (three), Microsporum canis (three) and T. tonsurans (two). We detected a higher
      rate of infection than that of the country's average.

PMID- 12801367
TI  - Dermatophytes isolated from domestic animals in Iran.
AB  - Between 1994 and 1998, a total of 790 feather, hair and skin specimens from a
      variety of animals with suspected dermatophytoses were studied, of which 248
      (31.4%) yielded dermatophytes. The most frequent dermatophytes isolated were
      Microsporum canis (38.3%), Trichophyton verrucosum (31.8%), T. mentagrophytes
      (13.3%) and M. gypseum (7.7%). There was a significantly higher proportion of
      positive cultures from cats (54.8%) than dogs (8.2%), and M. canis was the most
      common species isolated (87.2 and 50% respectively). Trichophyton verrucosum was
      the most frequent causative agent of dermatophytoses in ruminants, M. equinum in
      horses, M. gypseum in rabbits, M. gallinae in chickens and T. mentagrophytes in
      pet squirrels.

PMID- 12801368
TI  - Isolation of dermatophytes and other keratinophilic fungi from soils of Jammu,
      India.
AB  - A total of 112 soil samples collected from various areas of Jammu, India, were
      screened for the prevalence of keratinophilic fungi and related dermatophytes.
      From 65 positive samples (58.1%), a total of six genera with 13 species were
      isolated.

PMID- 12801369
TI  - Paracoccidioidomycosis and larynx carcinoma.
AB  - Report of a case of paracoccidioidomycosis associated with a carcinoma: both
      located in the larynx in a patient whose therapeutic response to antifungal
      treatment produced a recovery of physical conditions. This case shows the
      importance of taking into account the diagnosis of paracoccidioidomycosis in all
      patients with problems in the larynx, especially those who inhabit or inhabited
      endemic areas of Paracoccidioides brasiliensis.

PMID- 12801371
TI  - Subcutaneous phaeohyphomycosis on face caused by Cladophialophora bantiana.
AB  - We report the case of a patient suffering from subcutaneous phaeohyphomycosis
      caused by Cladophialophora bantiana. The face of the upper site was involved with
      small, stellate, pyogranulomatous foci and low inflammation. The patient was
      treated by topical and systemic corticosteriod and amphotericin B. After 3 months
      of treatment, the patient showed good response.

PMID- 12801370
TI  - Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole
      plus terbinafine, without the need for radical surgery.
AB  - Scedosporium prolificans infections of normal hosts usually require extensive
      debridement and sometimes amputation to effect cure, due to the intrinsic
      resistance of this species to available antifungal agents. Newer agents have not
      tested favourably. Variable results are obtained with voriconazole, and 100%
      resistance is described with echinocandins. Itraconazole and terbinafine has
      offered synergy against various moulds including S. prolificans. In vivo success
      is reported with the azole/terbinafine combination in S. apiospermum pulmonary
      infection and Pythium insidiosum periorbital cellulitis. We report a case of
      orthopaedic infection in a non-immunocompromised host with S. prolificans, in
      which the combinations of itraconazole/terbinafine and voriconazole/terbinafine
      showed synergy in vitro, and success was achieved without radical surgery, using
      voriconazole and terbinafine.

PMID- 12801372
TI  - Leukocytopenia after administration of itraconazole.

PMID- 12801373
TI  - Liberating the talents: whose talents and for what purpose?

PMID- 12801374
TI  - The creativity challenge.

PMID- 12801375
TI  - Changes in nursing identities: supporting a successful transition.
AB  - This article examines the role of nurse managers in delivering the NHS
      modernization agenda by supporting the development of new and innovative nursing
      roles as proposed in recent health care policy. A study by Ewens (1998) indicates
      that nurses will respond positively to new short-term developments because of the
      ability to re-conceptualize work roles before actually undertaking them, but that
      long-term success will depend upon whether the workplace provides the scope and
      flexibility for integration of new identities into the self-concept. It is argued
      that when nurses find a gap between what they believe their role could be and
      what in reality it is allowed to be they separate their self-concept from their
      work role. In this situation the nurse experiences frustration and disappointment
      and the work role becomes 'untenable', resulting in them either leaving or
      retreating back into traditional professional identities. A discussion is
      provided on the role of nurse managers in the prevention of this negative
      response by supporting innovative work environments that can accommodate the new
      roles envisaged in the current policy. The paper concludes with consideration of
      the current direction of nursing and questions whether this move towards the
      nurse as 'assistant physician' will, in the longer term, be a good thing for
      patients.

PMID- 12801376
TI  - What blocks health visitors from taking on a leadership role?
AB  - Current government documents in the United Kingdom call for all nurses to take on
      a greater leadership role. This paper critically considers some of the management
      factors that block one group of specialist nurses (health visitors) from
      fulfilling their leadership role. Health visitors have a key role to play in
      meeting the public health targets of local primary care trusts, known as local
      health improvement plans. But to take on a greater public health role, health
      visitors need to move away from working independently within separate general
      practitioner surgeries and to work in teams which share the vision and goals of
      the primary care trusts. The paper explores different styles of management that
      promote transformational leadership and relate to practice. It is suggested that
      use of the Servant-Leader model of management should encourage the empowerment of
      staff, and through empowerment health visitors should be able to instigate change
      and become more innovative in their practice. Persistent recruitment and
      retention problems have resulted in little time being available to focus on the
      effectiveness of services. The future management of health visitors will be to
      primarily run the service while supporting staff in accessing and influencing
      those in power.

PMID- 12801377
TI  - Participation of professional categories when reorganizing two hospitals--a
      comparative study and an evaluation.
AB  - BACKGROUND: At one University Hospital in Sweden (Hospital A) a new organization
      had been in effect for 4 years. The main characteristics were patient care
      departments managed by nurses, consisting of five wards serving organ-specific
      centres, which were organized in specialized departments managed by physicians.
      At another University Hospital (Hospital B) a reorganization was in the final
      planning process. DESIGN: This qualitative study evaluated and compared the
      process of planning and preparing reorganization at the two hospitals and
      evaluated the new organization at Hospital A. FINDINGS: Results show that all
      professional categories were involved all through the planning and preparing
      process at Hospital A. At Hospital B only physicians were involved. The goals set
      by the group planning the new organization at Hospital A had been achieved
      regarding cost effectiveness, personnel development, quality improvement in
      nursing care as well as other aspects. Nurses and nurse assistants were, for the
      most part, satisfied with the new organization and if unsatisfied, this was
      because of other factors. Physicians, in most cases, wanted a physician as
      manager on the level between the patient care department and the director.

PMID- 12801378
TI  - Stepping outside the stereotype. A pilot study of the motivations and experiences
      of males in the nursing profession.
AB  - Despite their historical significance to the UK's nursing profession, numbers of
      registered male nurses here have seldom exceeded 10% of the total. This is not an
      immutable principle, given that countries such as the Netherlands manage to
      attract males to the profession in much greater numbers. This paper examines and
      critiques the available literature on males in nursing from both a historical and
      present day perspective. In so doing, it discusses factors such as caring, over
      performance and career progression, and, notions of masculinity. It then moves on
      to outline and discuss an on-going pilot study specifically designed to examine
      the motivations and experiences of a sample of preregistration and
      postregistration male nurses in the UK, across a range of ages and ethnicities.
      The ultimate aim of the study is to produce evidence which will advance the
      recruitment of men to a profession which is currently experiencing severe
      recruitment difficulties. The paper presents themes emerging from the study to
      date, examining the implications these may have for the future management of
      nurse recruitment.

PMID- 12801379
TI  - A source of strength--nurses' perspectives of the perioperative dialogue.
AB  - AIM: To describe nurse anaesthetists' and theatre nurses' experiences of working
      with the perioperative dialogue. BACKGROUND: A new way of working in the
      perioperative context is the 'perioperative dialogue model', which is the meeting
      between the nurse and the patient before, during and after a patient's surgery.
      METHOD: Semi-structured interviews were conducted with 20 nurses, trained in
      working with the perioperative dialogue. Data were analysed according to grounded
      theory. FINDINGS: One core category, 'source of strength', and two main
      categories, 'walking together' and 'creating a caring relation', were defined.
      These represented factors in developing nurses' work and professional competence.
      The nurses became more committed to their work when they came to know the person
      beyond the character of the patient. CONCLUSIONS: The perioperative dialogue is a
      source of strength to the nurses. It is necessary that the organization supports
      nurses in this new way of working.

PMID- 12801380
TI  - Seeking the attitudes and perceptions of the Greek primary-care professionals on
      voluntary work in caring for people with HIV/AIDS.
AB  - BACKGROUND: During the last two decades Greece has moved towards a national
      health system. However, in a country with limited economic resources the
      necessity for reducing the increasing costs of the health care services by an
      effective use of available human resources, such as community volunteers, becomes
      inevitable. This paper reports the findings of a pilot study on attitudes and
      perceptions of primary-care staff towards voluntary work for human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.
      METHODS: Of the 300 primary-care professionals who are serving the health centres
      of the largest area of Athens, a sample of 153 was selected. The population
      surveyed was predominately female (n = 104, 69.3%) and most of them (n = 77,
      50.7%) were between 31 and 40 years of age. A 28-item questionnaire was used,
      especially designed to investigate attitudes and perceptions of primary health
      care (PHC) professionals regarding the contribution of volunteers to HIV/AIDS
      related programmes. RESULTS: Most of the respondents (n = 131, 85.6%) reported
      little or no experience of caring for HIV/AIDS patients and only 14 (9%) reported
      participation in any voluntary programmes. Eighty-eight per cent of patients (n =
      135) consider the participation of volunteers in AIDS programmes as very useful
      and the vast majority of the participants pointed out the usefulness of the
      participation of health professionals and other influencing persons in voluntary
      programmes. Participants also suggested that sharing time with HIV patients and
      families, offering emotional support and practical help and distributing
      information leaflets for the general population should be the volunteers'
      contribution in AIDS-related programmes. The PHC professionals' role in voluntary
      programmes is considered by the 91 respondents (59.5%) as 'planning and
      organizing', for 66 (43.1%), 'coordinating' and for 37 (24.2%), 'supporting'.
      Although the majority of the participants (n = 90, 58.8%) said they would
      participate as a volunteer in an AIDS-related programme, only one-third of the
      total sample (n = 48, 31.4%) agree with the statement that they have a
      professional duty to support such a type of programme. CONCLUSIONS: Primary-care
      workers present little experience in caring for HIV/AIDS patients or
      participating in volunteer programmes and mainly positive attitudes and
      perceptions to voluntary work. Continuing educational programmes together with
      awareness activities may increase the involvement of primary-care professionals
      in the effective management of AIDS in Greece.

PMID- 12801381
TI  - Florence Nightingale as 'mentor of matrons': correspondence with Rachel Williams
      at St Mary's Hospital.
AB  - This paper is based mainly on archival research. It is focused on letters from
      Florence Nightingale to one of her favourites, Rachel Williams, the reforming
      19th century matron of St Mary's Hospital, Paddington, who established the nurse
      training school in 1877. Discussion centres on Miss Nightingale's mentoring of
      Miss Williams, both in terms of personal/pastoral and more objective management
      advice. The discussion is then related to current theories of mentoring in nurse
      management. It would appear that Nightingale and modern mentors follow the same
      main precept of 'having the best interests of the mentored person at heart'.
      Differences relate more to style of expression than to the basic principles of
      mentorship.

PMID- 12801382
TI  - Management of change through force field analysis.
AB  - Today's NHS is rapidly changing, placing more emphasis on the managerial
      responsibilities of ward managers. Managing change is seen as being skilled at
      creating, acquiring and transferring knowledge to reflect new knowledge and
      insights. Defining core concepts is often difficult and requires the drawing on
      models/theories of change for guidance. Guidance from Lewin's (1951) force field
      analysis demonstrates the complexities of the change process and how driving and
      resisting forces were incorporated within the planning and implementation phases.
      Findings outline the benefits of a small scale change for staff, patients and the
      organization when successfully used to introduce a change of shift pattern within
      a progressively busy haematology day unit, in order to meet service demands
      without additional funding. Conclusions have been drawn in relation to the
      process and recommendations for practice made to further enhance care delivery
      within the unit.

PMID- 12801383
TI  - Nurse managers and peer supervision.

PMID- 12801384
TI  - Early diagnosis of Alzheimer's disease: clinical and economic benefits.
AB  - An estimated four million individuals in the United States have Alzheimer's
      disease (AD). This number is expected to more than triple by mid-century. Primary
      care physicians have a key role in evaluating older patients for early signs of
      dementia and in initiating treatment that can significantly retard its
      progression over the maximum period of time. That role and its challenges will
      inevitably grow along with the expected increase in the population aged 65 and
      older. The tendency for physicians to dismiss memory complaints as normal aging
      must be replaced by awareness of the need to assess and possibly intervene. Early
      intervention is the optimal strategy, not only because the patient's level of
      function will be preserved for a longer period, but also because community
      dwelling patients with AD incur less societal cost than those who require long
      term institutional placement. Institutionalization contributes heavily to the
      annual cost of care for AD in the United States, which is estimated to be 100
      billion dollars annually.

PMID- 12801385
TI  - Alzheimer's disease: current pharmacotherapy in the context of patient and family
      needs.
AB  - The objective of this paper is to review current evidence and treatment patterns
      for pharmacotherapy in Alzheimer's disease (AD), with an emphasis on outcomes
      considered important to patients and families. The sources for the information
      are the peer-reviewed literature, Food and Drug Administration-approved package
      labeling for acetylcholinesterase inhibitors (AChEIs), expert opinions expressed
      at the First Annual Dementia Congress, and clinical experience. Three AChEI
      agents are in routine use in the United States. They are considered part of the
      standard of care for patients with mild-to-moderate AD. There are differences in
      metabolism, pharmacokinetics, side effects, and ease of use that may influence
      the prescriber's choice of agent and dosage. The three approved agents have
      similar outcomes in cognition and global clinician ratings of effectiveness in
      double-blind placebo controlled trials. Persistent therapy with effective doses
      of AChEIs is associated with reduced risk for, or delayed, nursing home
      placement, which is a stated priority of AD caregivers. Agents from this class of
      drugs have also been shown to be associated with statistically significant
      preservation of daily function and benefits in treatment of adverse behaviors in
      AD. Numerous additional choices are available to the clinician for
      pharmacotherapy of adverse behaviors. Community-based psychoeducational support
      is also of value to caregivers.

PMID- 12801386
TI  - Vascular dementia: distinguishing characteristics, treatment, and prevention.
AB  - Vascular dementia (VaD) is the second-most-common cause of dementia in the
      elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive
      function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due
      to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the
      following criteria: cognitive loss, often predominantly subcortical; vascular
      brain lesions demonstrated by imaging; a temporal link between stroke and
      dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused
      by large-vessel disease with multiple strokes (multiinfarct dementia) or by a
      single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD
      caused by small-vessel occlusions with multiple lacunas and by hypoperfusive
      lesions resulting from stenosis of medullary arterioles, as in Binswanger's
      disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but
      memory impairment is mild or may not even be present. The cholinesterase
      inhibitors used for AD are also useful in VaD. Prevention strategies should focus
      on reduction of stroke and cardiovascular disease, with attention to control of
      risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and
      hyperhomocysteinemia.

PMID- 12801387
TI  - Medical management of advanced dementia.
AB  - A cure for Alzheimer's disease (AD) is still far off, and clinicians face the
      burden of caring for patients at all stages of dementia for the foreseeable
      future. Those with advanced disease suffer neurological symptoms and signs that
      include incontinence; problems with gait and mobility; marked cognitive,
      language, and functional impairment; and in about 90% of patients, significant
      behavior problems. Dementia precludes the ability to initiate meaningful
      activities or social interactions. Whether patients are resident in the community
      or living in a nursing home, this composite reflects a highly complex medical and
      neuropsychiatric management challenge. Predictable medical conditions also must
      be addressed (i.e., those that accompany dementia, such as parkinsonism, and
      those that are prevalent in any aging population, such as hypertension).
      Clinicians can better address these problems with awareness of current treatment
      options. Placebo-controlled trials of some psychotropic agents have shown modest
      favorable effects on behavior problems. Use of acetylcholinesterase inhibitors
      (AChEIs) to treat cognitive impairment and secondary behavioral symptoms derives
      primarily from results of placebo-controlled clinical trials. Trials in patients
      with moderate to severe AD, outpatients as well as nursing home residents, show
      overall effects similar to those seen in outpatients with milder dementia.
      Treatment with AChEIs may delay institutional placement. Memantine has shown
      benefit in trials in moderate to severe dementia, although it is not yet approved
      in the United States. Emerging data have expanded physicians' ability to use
      pharmacotherapy in patients with advanced dementia. Physicians need to enact the
      principle that something can be done for our afflicted parents and grandparents.

PMID- 12801388
TI  - Pathology and pathways of Alzheimer's disease with an update on new developments
      in treatment.
AB  - As our understanding of the complex pathology of Alzheimer's disease improves,
      more targets for therapy emerge. These include the actions of beta amyloid, the
      inflammatory cascade, pathobiology of tau proteins' conversion to neurofibrillary
      tangles, oxidative neuronal damage, and neurotransmitter depletion. Many agents
      now under investigation target the early stages of the disease process, aiming to
      prevent or slow the development of symptoms. This article reviews the current
      understanding of the course and pathology of Alzheimer's disease as it relates to
      emerging therapies, then summarizes some promising current research directions in
      primary prevention, secondary prevention, and treatment.

PMID- 12801390
TI  - Thinking bigger about research.

PMID- 12801392
TI  - Older men's experiences of living with severe visual impairment.
AB  - BACKGROUND: Little is known about how men react to their health and illness
      experiences. Lack of information about the lives of older men is unfortunate
      considering the anticipated growth of the older male sector of society and the
      fact that older men age differently than older women. One health-related
      experience common to many older men is severe visual impairment caused by macular
      degeneration, a chronic eye disease that affects central vision. Understanding
      the health experiences of older men is imperative if nurses are to provide
      quality care to this growing segment of society. AIM: The purpose of this study
      was to gain an understanding of the experience of severe visual impairment from
      the perspective of older men with macular degeneration. METHOD: A
      phenomenological approach was used to investigate the experience of severe visual
      impairment in eight older men with macular degeneration. Data were gathered
      through audiotaped interviews and analysed using a modified Giorgi method.
      FINDINGS: The resultant general structural description revealed six central
      themes: (1) older men's lives were circumscribed by what they could and could not
      see and could and could not do, (2) cherishing of independence, (3) creation of
      strategies, (4) acknowledgment of the progression of visual impairment, (5)
      confrontation of uncertainties, skepticism, and fears about their diagnosis and
      treatment, and (6) persistence with hope and optimism. CONCLUSIONS: A thorough
      nursing history and assessment must be completed, including information about the
      progression of the visual impairment, strategies used for living with visual
      loss, and presence of other health problems that may complicate life with visual
      impairment. Nurses must be aware that older men with macular degeneration are
      often sceptical about their diagnosis and treatment. Therefore, careful education
      and clear communication are essential.

PMID- 12801393
TI  - Deconstructing risk assessment and management in mental health nursing.
AB  - RATIONALE: Risk assessment and management have a taken a central position in the
      delivery of contemporary mental health services. However, these concepts are
      generally taken-for-granted as necessary and unavoidable aspects of mental health
      nursing practice. This deconstructive analysis explores some of the assumptions
      and values that underpin these concepts. AIMS: The aims of the study were to
      provide a deconstructive analysis of the concepts of risk and risk management,
      and to explore the historical context of mental disorder and the concept of risk,
      the clinical context of risk assessment and management, the cultural, political
      and economic context of risk, and the impact on mental health nursing and
      consumers of mental health services. DESIGN: This paper takes a deconstructive
      approach to the exploration of the historical, clinical, cultural, political and
      economic context of the concept of risk and its assessment and management. This
      is undertaken by providing a critical review of the history of mental illness and
      its relationship to risk, examination of government policy on clinical risk
      management, analysis of a risk assessment model and a discussion of the political
      and economic factors that have influenced the use of risk assessment and
      management in clinical practice. FINDINGS: The concept of risk and its assessment
      and management have been employed in the delivery of mental health services as a
      form of contemporary governance. One consequence of this has been the positioning
      of social concerns over clinical judgement. The process employed to assess and
      manage risk could be regarded as a process of codification, commodification and
      aggregation. In the mental health care setting this can mean attempting to
      control the actions and behaviours of consumers and clinicians to best meet the
      fiscal needs of the organization. CONCLUSION: The mental health nursing
      profession needs to examine carefully its socially mandated role as guardians of
      those who pose a risk to others to ensure that its practice represents its
      espoused therapeutic responsibilities.

PMID- 12801394
TI  - Exploring the beliefs and experiences of potential egg share donors.
AB  - BACKGROUND: To date there are few attitudinal studies of women's experiences of
      egg donation, motivation to donate or their thoughts about eggs donated. Studies
      are predominantly discussed in terms of a specific treatment option and the
      ethical implications of different treatments. These studies are mainly designed
      by professionals working in assisted reproductive technology in line with a
      clinical agenda. AIM: This study aimed to explore the beliefs and experiences of
      potential egg share donors using an interpretative phenomenological methodology
      to equip health care practitioners to deal better with patients' needs and
      desires. METHOD: Open-ended interviews were conducted immediately following
      introductory consultations with 11 potential egg share donors from one fertility
      centre in the United Kingdom (UK). The sample was opportunistic. Data collection
      took 8 months and van Manen's interpretative phenomenological method was used.
      FINDINGS: Analysis revealed six themes of egg sharing: motherhood (the
      predominant theme within which all other themes could be subsumed), context,
      doubt, coping, exchange and empathy. Themes illustrated women's continuation with
      the scheme despite fears about giving away eggs, the parenting skills of
      recipient couples and future repercussions of positive outcomes for donor and
      recipient. CONCLUSIONS: Egg sharing could be seen as a marker of hope. Buoyed up
      by the possibility of a successful outcome, women are prepared to undertake
      repetitive treatment attempts despite continued failure to conceive and knowledge
      of a slim chance of a positive outcome. Implications for practice, policy and
      ethics result in recommendations for more in-depth interview work by independent
      researchers to gain a clearer picture of women's responses to reproductive
      technologies and the development of services in line with patient need and
      individual expectation.

PMID- 12801395
TI  - Ethical issues in qualitative health research with homeless youths.
AB  - BACKGROUND: There is a need for increased guidance for the ethical conduct of
      qualitative research with vulnerable populations such as homeless youths. AIM:
      The purpose of this paper is to provide an overview of the main ethical
      challenges of conducting qualitative research with homeless youths and to propose
      possible solutions to these challenges. METHODS: This paper was informed by a
      review of professional guidelines for the ethical conduct of adolescent health
      research, national (US) and international bioethics bibliographical searches, and
      personal experience with qualitative research with homeless youths. FINDINGS: The
      main ethical challenges of conducting qualitative research with homeless youths
      include establishing and maintaining healthy researcher roles and boundaries,
      addressing the risks of researcher burn-out and safety issues, assuring optimal
      confidentiality, and avoiding sensationalism and voyeurism. CONCLUSION: It is
      important for qualitative researchers who work with vulnerable populations to
      ensure that research is conducted in the most ethical way possible.

PMID- 12801396
TI  - Follow-up for people with cancer: nurse-led services and telephone interventions.
AB  - BACKGROUND: Questions about the suitability of traditional outpatient follow-up
      clinics as a way of providing on-going monitoring for patients following serious
      illness have led to the development of a range of nurse-led services. However,
      there has been little attempt to draw some of this knowledge together formally
      and consider the weight of evidence on the necessity and value of nurse-led
      follow-up. AIM: To provide a review of literature evaluating the impact of nurse
      led follow-up in cancer care, with particular focus on the use and value of
      telephone interventions. METHOD: A literature search was conducted of nursing,
      medical and social science databases and the following keywords: cancer follow
      up, nurse-led follow-up, telephone follow-up, telephone-based interventions and
      telephone survey. The search yielded over 150 papers, of which 37 were relevant
      to this review. FINDINGS: The literature suggests that nurse-led follow-up for
      people with cancer meets their needs for psychological support and information.
      The telephone is identified as a suitable means of providing this kind of
      service. CONCLUSION: This review demonstrates that nurse-led follow-up services
      are acceptable, appropriate and effective. Combined with use of the telephone,
      such services can be an efficient means of maintaining contact with a large
      client group, providing vital support to vulnerable patients during their move
      into aftercare and beyond.

PMID- 12801397
TI  - Self-directed learning in nurse education: a review of the literature.
AB  - RATIONALE: Self-directed learning is essential in assisting nurses to meet the
      challenges presented in today's health care environment. Nurse educators have an
      important role to play in assisting nurses to acquire the skills for self
      directed learning, and to do this they need to understand the concept of self
      directed learning. AIM: The aim of this review is to explore the concept of self
      directed learning and its use in nurse education. METHODS: A review of the
      literature was conducted using CINAHL, Medline and other databases and the
      keywords 'self-directed learning', 'student nurses', 'classroom', 'nursing
      education' and 'adult education'. FINDINGS: The concept of self-directed learning
      is based on the principles of adult education and can take many different
      formats. Self-directed learning has many benefits. However, acquiring the
      necessary skills is dependent on a students' preference and readiness for self
      directed learning and nurse educators' implementation of the concept. In
      implementing self-directed learning, nurse educators become facilitators of
      learning and require ongoing staff development. Not all students are self
      directed and a variety of teaching methods should be used in curricula.
      CONCLUSIONS: A consensus definition of the concept of lifelong learning does not
      exist, and students and teachers may have different perspectives on it. Mature
      students may be more self-directing than school-leavers, and learning styles and
      readiness to learn need to be assessed when judging the appropriateness of using
      self-directed learning approaches. However, there are many potential benefits,
      including increased confidence, autonomy, motivation and preparation for lifelong
      learning.

PMID- 12801398
TI  - A longitudinal cohort study of burnout and attrition in nursing students.
AB  - BACKGROUND: It is well-established that stress is likely to contribute to
      attrition in nursing students. Attrition from nursing programmes and retention of
      nurses in the profession are international concerns and steps are currently being
      taken in the United Kingdom to tackle these issues. AIM: The aim of this study
      was to investigate prospectively the determinants of, and relationships among,
      stress, burnout and attrition in nursing students. METHOD: A longitudinal design
      involving a complete cohort of nursing students was employed, using a battery of
      instruments to measure personality, intelligence, psychological morbidity,
      stress, coping and burnout. Data were gathered on entry, at 12 and 24 months, and
      at the end of the nursing programme. FINDINGS: Students experienced increasing
      levels of stress and use of negative coping mechanisms as the programme
      progressed and psychological morbidity increased. Positive aspects of personality
      were more likely to lead to aspects of burnout, and personality was a more
      important indicator of attrition than cognitive ability. CONCLUSIONS: Stress,
      burnout and attrition may not be directly linked. Personality factors at course
      entry contributed significantly to the prediction of burnout and programme
      completion, but the relationships were not strong enough to be practically
      useful.

PMID- 12801399
TI  - A structured health needs assessment tool: acceptability and effectiveness for
      health visiting.
AB  - BACKGROUND: There is, nominally at least, a universal health visiting service in
      Great Britain, although the frequency of contacts may be severely restricted.
      Debates about whether home visiting should be universal or selective, therefore,
      focus on whether health visitors should use professional judgement or structured
      assessment tools to target attention within their caseload. Research attention
      has focused mainly on unstructured needs assessments and professional judgment or
      the development of assessment tools, so that the views of practitioners using
      structured instruments and their clients are not known. METHODS: A two-phase
      qualitative study examined the acceptability and effectiveness of a structured
      health needs assessment tool (HNAT) implemented in London. Views about the tool
      were elicited from 30 health visitors through telephone interview, and then 21
      assessments were observed and tape-recorded; 19 clients were interviewed after
      the event. Data were evaluated for adequate coverage of views across the target
      population and analysed using the framework approach. FINDINGS: A range of views
      were expressed, but the HNAT caused anxiety and distress to, particularly, the
      most vulnerable clients. The structured format of the tool appeared to encourage
      the health visitors to question instead of listen. It did not help to identify
      all the needs and intruded into normal practice in an insensitive and unhelpful
      way. LIMITATIONS: This study investigated only one form of structured HNAT. These
      are commonly used to prioritize undifferentiated needs of clients who have been
      offered an unsolicited, health promoting service. Our findings therefore do not
      apply to validated instruments used for screening or specific diagnostic purposes
      where a client has requested help with a problem. CONCLUSIONS: Given the problems
      in use and potential for harm, this form of structured assessment tool appears
      unsuitable for routine use to determine the intensity of health visiting
      contacts.

PMID- 12801400
TI  - Career choice in nursing students: gendered constructs as psychological barriers.
AB  - BACKGROUND: Gendered views of nursing remain widespread. This study explores how
      such views may influence student nurses' career aspirations. METHOD: A group of
      preregistration student nurses completed a questionnaire distributed early in
      their first year of study of a 3 year Higher Diploma in Nursing. Data were
      gathered on career aspirations and the perceived gendered nature of a number of
      career options. Gender role orientation and occupational and academic self
      efficacy were also measured using the Bem Sex Role Inventory and an adaptation of
      the Betz and Hackett Self-Efficacy Scale. RESULTS: The results document the
      relative popularity of each specialism within nursing and students' perceptions
      of the gendered nature of each of the various nurse careers. Differences in these
      perceptions as related to gender and gender role identity are also outlined.
      Gender and gender role orientation were found to be predictive of sex-typed
      career aspirations only. CONCLUSION: The psychological barriers that exist for
      both men and women as they pursue careers in nursing need to be addressed if the
      current shortage of nursing personnel across the United Kingdom (UK) is to be
      solved.

PMID- 12801401
TI  - Being professional and being human: one nurse's relationship with a psychiatric
      patient.
AB  - BACKGROUND: The theoretical foundations and professional ideals of psychiatric
      nursing contain built-in contradictions. One central ideal is that nurses should
      use themselves as therapeutic instruments. The expectation that nurses should
      have both a professional and a human function is examined in this study. PURPOSE:
      The purpose of this study was to find out how nurses experience and interpret the
      contradictory demands of being both fellow human being and health professional in
      their work with patients. METHODS: An ethnographic research design including
      participant observation and narrative interviews with nurses working on an acute
      ward of a psychiatric hospital was used. The case of one nurse is analysed and
      discussed. FINDINGS: The study shows that when nurses themselves are 'therapeutic
      instruments', tensions are created. Contradictory demands produce difficult role
      conflicts. Nurses vary in the ways in which they interact with patients. The
      study shows how the nurse's own vulnerability can be a constructive element in
      patient care. It also shows that although the nurse is aware of this, she is also
      critical of her performance, feeling that it falls short of accepted professional
      standards. Her colleagues reinforce these standards. CONCLUSION: The ideal that
      psychiatric nursing should be a balancing act between intimacy and distance,
      between human and professional ways of acting, appears to be too harmonious and
      narrow a one. The study suggests that there is potential for professional
      development if nurses are able to recognize their own vulnerability. Critical
      examination and discussion of conventionally accepted ideals can help develop our
      knowledge of the profession.

PMID- 12801403
TI  - Ira.
AB  - For a quarter of a century in genetics if you said Ira the chances were you meant
      Ira Herskowitz. When he died, on April 28 this year, it left a hole in the fields
      of genetics and genomics the size of the Grand Canyon.

PMID- 12801402
TI  - Risk of valvular heart disease associated with use of fenfluramine.
AB  - BACKGROUND: Estimates of excess risk of valvular heart disease among prior users
      of fenfluramine and dexfenfluramine have varied widely. Two major forms of bias
      appear to contribute to this variability and also result in a systematic under
      estimation of risk. The first, a form of nondifferential misclassification, is
      the result of including background, prevalent cases among both exposed and
      unexposed persons in calculations of risk. The second bias results from not
      considering the relatively short duration of exposure to drugs. METHODS: We
      examined data from all available echocardiographic studies reporting the
      prevalence of aortic regurgitation (AR) and mitral regurgitation (MR) among
      persons exposed to fenfluramine or dexfenfluramine and a suitable control group.
      We also included one study in which previously existing AR or MR had been
      excluded. We corrected for background prevalent cases, estimated incidence rates
      in unexposed persons, and performed a person-years analysis of apparent incidence
      rates based on exposure time to provide an unbiased estimate of relative risk.
      RESULTS: Appearance of new AR was strongly related to duration of exposure (R2 =
      0.75, p < 0.0001). The summary relative risk for mild or greater AR was 19.6 (95%
      CI 16.3-23.5, p < 0.00001); for moderate or greater MR it was 5.9 (95% CI 4.0
      8.6, p < 0.00001). CONCLUSION: These findings provide strong support for the view
      that fenfluramine and dexfenfluramine are potent causal factors in the
      development of both aortic and mitral valvular heart disease.

PMID- 12801405
TI  - The Neurospora crassa genome opens up the world of filamentous fungi.
AB  - The filamentous fungus Neurospora crassa, which has played an important role in
      the development of modern genetics, has several unique genome-defense mechanisms,
      including a process called repeat-induced point mutation. The draft genome
      sequence has revealed several unusual features, which suggest that the evolution
      of N. crassa has been greatly influenced by these defense mechanisms.

PMID- 12801404
TI  - Matrix metalloproteinases: old dogs with new tricks.
AB  - The matrix metalloproteinase family in humans comprises 23 enzymes, which are
      involved in many biological processes and diseases. It was previously thought
      that these enzymes acted only to degrade components of the extracellular matrix,
      but this view has changed with the discovery that non-extracellular-matrix
      molecules are also substrates.

PMID- 12801406
TI  - What makes a mitochondrion?
AB  - Experimental analyses of the proteins found in the mitochondria of yeast, humans
      and Arabidopsis have confirmed some expectations but given some surprises and
      some insights into the evolutionary origins of mitochondrial proteins.

PMID- 12801408
TI  - Assembling a jigsaw puzzle with 20,000 parts.

PMID- 12801407
TI  - The genomics and proteomics of biofilm formation.
AB  - Bacterial communities that are attached to a surface, so-called biofilms, and
      their inherent resistance to antimicrobial agents are a cause of many persistent
      and chronic bacterial infections. Recent genomic and proteomic studies have
      identified many of the genes and gene products differentially expressed during
      biofilm formation, revealing the complexity of this developmental process.

PMID- 12801409
TI  - Translating genome sequences into biological understanding.

PMID- 12801410
TI  - The mosaic structure of the symbiotic plasmid of Rhizobium etli CFN42 and its
      relation to other symbiotic genome compartments.
AB  - BACKGROUND: Symbiotic bacteria known as rhizobia interact with the roots of
      legumes and induce the formation of nitrogen-fixing nodules. In rhizobia,
      essential genes for symbiosis are compartmentalized either in symbiotic plasmids
      or in chromosomal symbiotic islands. To understand the structure and evolution of
      the symbiotic genome compartments (SGCs), it is necessary to analyze their common
      genetic content and organization as well as to study their differences. To date,
      five SGCs belonging to distinct species of rhizobia have been entirely sequenced.
      We report the complete sequence of the symbiotic plasmid of Rhizobium etli CFN42,
      a microsymbiont of beans, and a comparison with other SGC sequences available.
      RESULTS: The symbiotic plasmid is a circular molecule of 371,255 base-pairs
      containing 359 coding sequences. Nodulation and nitrogen-fixation genes common to
      other rhizobia are clustered in a region of 125 kilobases. Numerous sequences
      related to mobile elements are scattered throughout. In some cases the mobile
      elements flank blocks of functionally related sequences, thereby suggesting a
      role in transposition. The plasmid contains 12 reiterated DNA families that are
      likely to participate in genomic rearrangements. Comparisons between this plasmid
      and complete rhizobial genomes and symbiotic compartments already sequenced show
      a general lack of synteny and colinearity, with the exception of some
      transcriptional units. There are only 20 symbiotic genes that are shared by all
      SGCs. CONCLUSIONS: Our data support the notion that the symbiotic compartments of
      rhizobia genomes are mosaic structures that have been frequently tailored by
      recombination, horizontal transfer and transposition.

PMID- 12801411
TI  - Differential gene-expression patterns in genital fibroblasts of normal males and
      46,XY females with androgen insensitivity syndrome: evidence for early
      programming involving the androgen receptor.
AB  - BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes
      from male infertility to complete feminization. Most individuals with AIS carry
      germline mutations of the androgen receptor (AR) that interfere with or ablate
      its function. As genital fibroblasts retain expression of the AR in vitro, we
      used genital skin fibroblasts from normal males and 46,XY females with complete
      AIS due to known AR mutations to gain insights into the role of the AR in human
      genital differentiation. RESULTS: Using DNA microarrays representing 32,968
      different genes, we identified 404 transcripts with significant differences in
      transcription levels between genital skin fibroblasts cultured from normal and
      AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression
      of genes involved in key processes of morphogenesis. On the basis of animal
      studies and human genetic syndromes, several of these genes are known to have
      specific roles in genital differentiation. Remarkably, genital fibroblasts from
      both normal and AIS-affected individuals showed no transcriptional response to
      dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The
      results suggest that in addition to differences in the anatomic origin of the
      cells, androgen signaling during prenatal development contributes to setting long
      lasting, androgen-independent transcriptional programs in genital fibroblasts.
      Our findings have broad implications in understanding the establishment and the
      stability of sexual dimorphism in human genital development.

PMID- 12801412
TI  - A phylogenetic study of cytochrome b561 proteins.
AB  - BACKGROUND: As an antioxidant and cofactor to numerous metabolic enzymes,
      ascorbate has an essential role in plants and animals. Cytochromes b561
      constitute a class of intrinsic membrane proteins involved in ascorbate
      regeneration. Despite their importance in ascorbate metabolism, no evolutionary
      analysis has been presented so far on this newly described protein family.
      RESULTS: Cytochromes b561 have been identified in a large number of
      phylogenetically distant species, but are absent in fungi and prokaryotes. Most
      species contain three or four cytochrome b561 paralogous proteins, and the
      encoding genes usually have four or five exons. At the protein level, sequence
      similarities are rather low between cytochromes b561 within a single species (34
      45% identity), and among phylogenetically distant species (around 30% identity).
      However, particular structural features characterizing this protein family are
      well conserved in members from all species investigated. These features comprise
      six transmembrane helices, four strictly conserved histidine residues, probably
      coordinating the two heme molecules, and putative ascorbate and monodehydro
      ascorbate (MDHA) substrate-binding sites. Analysis of plant cytochromes b561
      shows a separation between those from monocotyledonous and dicotyledonous species
      in a phylogenetic tree. CONCLUSIONS: All cytochromes b561 have probably evolved
      from a common ancestral protein before the separation of plants and animals.
      Their phyletic distribution mirrors the use of ascorbate as primary antioxidant,
      indicating their role in ascorbate homeostasis and antioxidative defense. In
      plants, the differentiation into four cytochrome b561 isoforms probably occurred
      before the separation between monocots and dicots.

PMID- 12801413
TI  - Horizontally transferred genes in plant-parasitic nematodes: a high-throughput
      genomic approach.
AB  - BACKGROUND: Published accounts of horizontally acquired genes in plant-parasitic
      nematodes have not been the result of a specific search for gene transfer per se,
      but rather have emerged from characterization of individual genes. We present a
      method for a high-throughput genome screen for horizontally acquired genes,
      illustrated using expressed sequence tag (EST) data from three species of root
      knot nematode, Meloidogyne species. RESULTS: Our approach identified the
      previously postulated horizontally transferred genes and revealed six new
      candidates. Screening was partially dependent on sequence quality, with more
      candidates identified from clustered sequences than from raw EST data.
      Computational and experimental methods verified the horizontal gene transfer
      candidates as bona fide nematode genes. Phylogenetic analysis implicated
      rhizobial ancestors as donors of horizontally acquired genes in Meloidogyne.
      CONCLUSIONS: High-throughput genomic screening is an effective way to identify
      horizontal gene transfer candidates. Transferred genes that have undergone
      amelioration of nucleotide composition and codon bias have been identified using
      this approach. Analysis of these horizontally transferred gene candidates
      suggests a link between horizontally transferred genes in Meloidogyne and
      parasitism.

PMID- 12801414
TI  - A method to assess compositional bias in biological sequences and its application
      to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes.
AB  - We have derived a novel method to assess compositional biases in biological
      sequences, which is based on finding the lowest-probability subsequences for a
      given residue-type set. As a case study, the distribution of prion-like
      glutamine/asparagine-rich ((Q+N)-rich) domains (which are linked to
      amyloidogenesis) was assessed for budding and fission yeasts and four other
      eukaryotes. We find more than 170 prion-like (Q+N)-rich regions in budding yeast,
      and, strikingly, many fewer in fission yeast. Also, some residues, such as
      tryptophan or isoleucine, are unlikely to form biased regions in any eukaryotic
      proteome.

PMID- 12801415
TI  - Statistical methods for ranking differentially expressed genes.
AB  - In the analysis of microarray data the identification of differential expression
      is paramount. Here I outline a method for finding an optimal test statistic with
      which to rank genes with respect to differential expression. Tests of the method
      show that it allows generation of top gene lists that give few false positives
      and few false negatives. Estimation of the false-negative as well as the false
      positive rate lies at the heart of the method.

PMID- 12801416
TI  - Apoptosis in uterine epithelium and decidua in response to implantation: evidence
      for two different pathways.
AB  - During the initial steps of implantation, the mouse uterine epithelium of the
      implantation chamber undergoes apoptosis in response to the interacting
      blastocyst. With progressing implantation, regression of the decidual cells
      allows a restricted and coordinated invasion of trophoblast cells into the
      maternal compartment. In order to investigate pathways of apoptosis in mouse
      uterine epithelium and decidua during early pregnancy (day 4.5-7.0 post coitum),
      we have investigated different proteins such as TNFalpha, TNF receptor1, Fas
      ligand, Fas receptor1, Bax and Bcl2 as well as caspase-9 and caspase-3 using
      immunohistochemistry. To detect cells undergoing apoptosis the Tunel assay was
      performed. Immunoreactivity for TNFalpha as well as for TNF receptor1 was
      observed exclusively in the epithelium of the implantation chamber and the
      adjacent luminal epithelium from day 4.5 post coitum onwards. In the developing
      decidua the Fas ligand, but not the Fas receptor, was expressed. Bax and Bcl2
      revealed a complementary expression pattern with Bax in the primary and Bcl2 in
      the adjacent decidual zone. Strong immunolabelling for the initiator caspase-9
      was restricted to the decidual compartment, whereas caspase-3 expression
      characterized the apoptotic uterine epithelium. Only some caspase-3 positive
      decidual cells were found around the embryo which correlated to the pattern of
      Tunel staining. Taken together, the apoptotic degeneration of the uterine
      epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas
      the very moderate regression of the decidua did not show the investigated death
      receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a
      different regulation for epithelial versus decidual apoptosis.

PMID- 12801417
TI  - Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison
      to the WOMAC in total knee replacement.
AB  - BACKGROUND: The Knee injury and Osteoarthritis Outcome Score (KOOS) is an
      extension of the Western Ontario and McMaster Universities Osteoarthrtis Index
      (WOMAC), the most commonly used outcome instrument for assessment of patient
      relevant treatment effects in osteoarthritis. KOOS was developed for younger
      and/or more active patients with knee injury and knee osteoarthritis and has in
      previous studies on these groups been the more responsive instrument compared to
      the WOMAC. Some patients eligible for total knee replacement have expectations of
      more demanding physical functions than required for daily living. This encouraged
      us to study the use of the Knee injury and Osteoarthritis Outcome Score (KOOS) to
      assess the outcome of total knee replacement. METHODS: We studied the test-retest
      reliability, validity and responsiveness of the Swedish version LK 1.0 of the
      KOOS when used to prospectively evaluate the outcome of 105 patients (mean age
      71.3, 66 women) after total knee replacement. The follow-up rates at 6 and 12
      months were 92% and 86%, respectively. RESULTS: The intraclass correlation
      coefficients were over 0.75 for all subscales indicating sufficient test-retest
      reliability. Bland-Altman plots confirmed this finding. Over 90% of the patients
      regarded improvement in the subscales Pain, Symptoms, Activities of Daily Living,
      and knee-related Quality of Life to be extremely or very important when deciding
      to have their knee operated on indicating good content validity. The correlations
      found in comparison to the SF-36 indicated the KOOS measured expected constructs.
      The most responsive subscale was knee-related Quality of Life. The effect sizes
      of the five KOOS subscales at 12 months ranged from 1.08 to 3.54 and for the
      WOMAC from 1.65 to 2.56. CONCLUSION: The Knee injury and Osteoarthritis Outcome
      Score (KOOS) is a valid, reliable, and responsive outcome measure in total joint
      replacement. In comparison to the WOMAC, the KOOS improved validity and may be at
      least as responsive as the WOMAC.

PMID- 12801418
TI  - Application of in situ reverse trancriptase-polymerase chain reaction (RT-PCR) to
      tissue microarrays.
AB  - Detection of disease-associated gene transcripts in primary disease tissues is
      frequently confounded by the presence of non-involved cell types. Alternative
      methods of detecting gene expression directly within tissues involve either the
      generation of antibodies, which can be a lengthy process and may suffer from lack
      of specificity, or amplification of reverse-transcribed cDNA in tissue sections
      (in situ RT-PCR). The latter method is highly specific and enables detection of
      transcripts in the cells originally responsible for their synthesis, but is
      highly destructive of tissue structures and can be carried out on only one or a
      few sections per experiment, resulting in low reproducibility. In this study, in
      situ RT-PCR was applied for the first time to commercially available tissue
      section microarrays enabling the examination of up to 70 different samples
      simultaneously. Modifications to the technique are detailed that preserved
      visible tissue and cellular structures and improved transcript detection whilst
      preventing significant generation of artefacts.

PMID- 12801419
TI  - ScanImage: flexible software for operating laser scanning microscopes.
AB  - BACKGROUND: Laser scanning microscopy is a powerful tool for analyzing the
      structure and function of biological specimens. Although numerous commercial
      laser scanning microscopes exist, some of the more interesting and challenging
      applications demand custom design. A major impediment to custom design is the
      difficulty of building custom data acquisition hardware and writing the complex
      software required to run the laser scanning microscope. RESULTS: We describe a
      simple, software-based approach to operating a laser scanning microscope without
      the need for custom data acquisition hardware. Data acquisition and control of
      laser scanning are achieved through standard data acquisition boards. The entire
      burden of signal integration and image processing is placed on the CPU of the
      computer. We quantitate the effectiveness of our data acquisition and signal
      conditioning algorithm under a variety of conditions. We implement our approach
      in an open source software package (ScanImage) and describe its functionality.
      CONCLUSIONS: We present ScanImage, software to run a flexible laser scanning
      microscope that allows easy custom design.

PMID- 12801420
TI  - Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa.
AB  - BACKGROUND: Many filarial nematodes harbour Wolbachia endobacteria. These
      endobacteria are transmitted vertically from one generation to the next. In
      several filarial species that have been studied to date they are obligatory
      symbionts of their hosts. Elimination of the endobacteria by antibiotics
      interrupts the embryogenesis and hence the production of microfilariae. The
      medical implication of this being that the use of doxycycline for the treatment
      of human onchocerciasis and bancroftian filariasis leads to elimination of the
      Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in
      the immunopathology of patients and may contribute to side effects seen after
      antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa
      loa. Since these results have been doubted, and because of the medical
      significance, several independent methods were applied to search for Wolbachia in
      L. loa. METHODS: Loa loa and Onchocerca volvulus were studied by electron
      microscopy, histology with silver staining, and immunohistology using antibodies
      against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The
      results achieved with L. loa and O. volvulus were compared. Searching for
      Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the
      FTSZ cell division protein, and WSP. RESULTS: No Wolbachia endobacteria were
      discovered by immunohistology in 13 male and 14 female L. loa worms and in
      numerous L. loa microfilariae. In contrast, endobacteria were found in large
      numbers in O. volvulus and 14 other filaria species. No intracellular bacteria
      were seen in electron micrographs of oocytes and young morulae of L. loa in
      contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not
      detected by PCR in three male and six female L. loa worms and in two
      microfilariae samples of L. loa. CONCLUSIONS: Loa loa do not harbour obligatory
      symbiotic Wolbachia endobacteria in essential numbers to enable their efficient
      vertical transmission or to play a role in production of microfilariae.
      Exclusively, the filariae cause the immunopathology of loiasis is patients and
      the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be
      used to cure loiais but it probably does not represent a risk for L. loa patients
      when administered to patients with co-infections of onchocerciasis.

PMID- 12801421
TI  - 'A mate or a meal'--pre-gravid behaviour of female Anopheles gambiae from the
      islands of Sao Tome and Principe, West Africa.
AB  - BACKGROUND: Malaria prevalence differs between the two islands that comprise the
      archipelago of Sao Tome and Principe. This may be due to differences in the
      biology of local Anopheles gambiae, the only vector on the islands. Survival rate
      and feeding frequency are two factors influencing vectorial capacity. Anophelines
      generally feed just once per gonotrophic (oviposition) cycle. Newly emerged
      insects, however, may feed two or more times during their first oviposition cycle
      thus increasing the likelihood of becoming infected. The reasons for multiple
      feeding are not clearly understood and it is still uncertain whether the
      behaviour is facultative or obligatory. We, therefore, determined survival and
      sporozoite rates, and examined the behaviour of An. gambiae from the two islands
      during their first gonotrophic cycle. METHODS: The wing size of 1,410, abdominal
      condition of 687, gonotrophic age and mated status of 7,264 female M form An.
      gambiae collected by light-trap, landing catch, resting outdoors or in copula,
      was determined from four sites in the archipelago. Sporozoite rates assessed by
      ELISA in 15,533 females from Sao Tome and 2,111 from Principe were determined.
      RESULTS: Estimated survival rates ranged between 0.834-0.849 per day in Sao Tome
      and 0.801-0.818 per day in Principe. Sporozoite rates of 0.63% in Sao Tome were
      significantly higher than the 0.24% from Principe. Overall 49% of females mated
      on the second night after emergence before feeding, and 51% on the third night
      and thus fed before mating. The likelihood of mating before feeding increased
      with wing size. None of the 3,776 parous insects collected showed evidence of
      recent mating. All but two of the 198 females collected in copula had undeveloped
      ovaries. Mean wing sizes and the number of insects collected in a sentinel light
      trap varied but the proportion of newly emerged insects in the collection did
      not. The estimated survival rate of the smallest insects was lower than other
      size groups, but the overall size distribution of each age group was normal.
      Parous insects were gonotrophically concordant. CONCLUSION: Differences in
      mosquito survival contributed to the lower sporozoite rates and endemicity of
      malaria on Principe compared to Sao Tome. On both islands all newly emerged
      insects blood fed on the second night following emergence but only became
      gonotrophically active on the third night after emergence. Smaller insects had a
      higher 'mortality/emigration' rate than larger ones. We suggest that
      insufficiency of Juvenile Hormone until the third day of adult life is
      responsible for gonotrophic inactivity and that by partitioning mating between
      the second or third day after emergence females maximise their chances of out
      crossing.

PMID- 12801422
TI  - Uptake of proteins and degradation of human serum albumin by Plasmodium
      falciparum-infected human erythrocytes.
AB  - BACKGROUND: Intraerythrocytic malaria parasites actively import obligate
      nutrients from serum and export proteins and lipids to erythrocyte cytoplasm and
      membrane. The import of macromolecules in the malaria parasite has been the
      subject of many debates. To understand the import of macromolecules by the
      parasite, we studied the uptake of proteins by Plasmodium falciparum infected
      human erythrocyte. METHODS: Proteins were biotin labelled individually, purified
      on a gel filtration column and added to uninfected and infected asynchronized
      culture. The uptake of these proteins by malaria parasites was determined by
      western blot analysis of parasite pellet and their different fractions using
      streptavidin-horseradish conjugate. To further confirm this import, we studied
      the uptake of 125I-labelled proteins by western blot analysis as well as used
      direct immunofluorescence method. RESULTS: Here we show that biotin labelled and
      radio-iodinated polypeptides of molecular sizes in the range of 45 to 206 kDa,
      when added in the culture medium, get direct access to the parasite membrane
      through a membrane network by by-passing the erythrocyte cytosol. The import of
      these polypeptides is ATP-dependent as sodium azide treatment blocks this uptake.
      We also show that malaria parasites have the ability to take up and degrade
      biotin labelled human serum albumin, which has been shown to be essential for the
      parasite growth. CONCLUSIONS: These results can be used, as a basis to explore
      the role of human serum albumin in the intraerythrocytic development of
      parasites, and this in turn can be an important adjunct to the development of
      novel antimalarial drugs.

PMID- 12801423
TI  - Characterization of the iron-regulated desA promoter of Streptomyces pilosus as a
      system for controlled gene expression in actinomycetes.
AB  - BACKGROUND: The bioavailability of iron is quite low since it is usually present
      as insoluble complexes. To solve the bioavailability problem microorganisms have
      developed highly efficient iron-scavenging systems based on the synthesis of
      siderophores that have high iron affinity. The systems of iron assimilation in
      microorganisms are strictly regulated to control the intracellular iron levels
      since at high concentrations iron is toxic for cells. Streptomyces pilosus
      synthesizes the siderofore desferrioxamine B. The first step in desferrioxamine
      biosynthesis is decarboxylation of L-lysine to form cadaverine, a desferrioxamine
      B precursor. This reaction is catalyzed by the lysine decarboxylase, an enzyme
      encoded by the desA gene that is repressed by iron. RESULTS: The binding of the
      DmdR (acronym for divalent metal dependent repressor) to the desA promoter in
      presence of Fe2+ or other divalent ions has been characterized. A 51 bp DNA
      fragment of the desA promoter containing the 9 bp inverted repeat was sufficient
      for binding of the DmdR repressor, as observed by the electrophoretic mobility
      shift assay. The desA mobility shift was prevented by neutralizing DmdR with anti
      DmdR antibodies or by chelating the divalent metal in the binding reaction with
      2,2'-dipyridyl. Binding to the desA promoter was observed with purified DmdR
      repressors of Streptomyces coelicolor or Rhodococcus fascians suggesting that
      there is a common mechanism of iron-regulation in actinomycetes. The complete
      desA promoter region was coupled using transcriptional fusions to the amy
      reporter gene (encoding alpha-amylase) in low copy or multicopy Streptomyces
      vectors. The iron-regulated desA promoter was induced by addition of the iron
      chelating agent 2,2'-dipyridyl resulting in a strong expression of the reporter
      gene. CONCLUSIONS: The iron-regulated desA promoter can be used for inducible
      expression of genes in Streptomyces species, as shown by de-repression of the
      promoter when coupled to a reporter gene.

PMID- 12801424
TI  - Optimization of biotinyl-tyramide-based in situ hybridization for sensitive
      background-free applications on formalin-fixed, paraffin-embedded tissue
      specimens.
AB  - BACKGROUND: Over the past five years in situ hybridization techniques employing
      tyramide amplification reagents have been developed and promise the potential
      detection of low/single-copy nucleic acid sequences. However the increased
      sensitivity that tyramide amplification brings about may also lead to problems of
      background staining that confound data interpretation. METHODS: In this study
      those factors enabling background-free biotinyl-tyramide based in situ
      hybridization assay of formalin-fixed paraffin-embedded tissues have been
      examined. SiHa, HeLa and CaSki cell lines known to contain HPV integrated into
      the cell genome, and archival cervical pre-invasive lesions and carcinomas have
      been successfully assessed using biotinylated HPV and centromeric probes.
      RESULTS: The single most important factor both for sensitivity and clean
      background was a tissue unmasking regimen that included treatment with 10 mM
      sodium citrate pH 6.0 at 95 degrees C followed by digestion with pepsin/0.2 M
      HCl. Concentrations both of probe and primary streptavidin-peroxidase conjugate
      and pH of hybridization mix and stringency washes were also critical for
      sensitivity. Certain probes were more associated with background staining than
      others. This problem was not related to probe purity or size. In these instances
      composition of hybridization mix solution was especially critical to avoid
      background. 3-amino-9-ethylcarbazole was preferred over 3,3'-diaminobenzidene as
      a chromogen because background was cleaner and the 1-2 copies of HPV16 integrated
      in SiHa cells were readily demonstrable. HPV detection on metaphase spreads
      prepared from SiHa cells was only successful when a fluorescent detection method
      was combined with tyramide reagent. 'Punctate' and 'diffuse' signal patterns were
      identified amongst tissues consistent with the former representing integration
      and 'diffuse' representing episomal HPV. Only punctate signals were detected
      amongst the cell lines and were common amongst high-grade pre-invasive lesions
      and carcinomas. However it remains to be determined why single/low-copy episomal
      HPV in basal/parabasal cells of low-grade lesions is not also detectable using
      tyramide-based techniques and whether every punctate signal represents
      integration. CONCLUSIONS: A tyramide-based in situ hybridization methodology has
      been established that enables sensitive, background-free assay of clinical
      specimens. As punctate signals characterize HPV in high-grade cervical lesions
      the method may have potential for clinical applications.

PMID- 12801425
TI  - Oligodeoxyribonucleotide probe accessibility on a three-dimensional DNA
      microarray surface and the effect of hybridization time on the accuracy of
      expression ratios.
AB  - BACKGROUND: DNA microarrays are now routinely used to monitor the transcript
      levels of thousands of genes simultaneously. However, the array fabrication
      method, hybridization conditions, and oligodeoxyribonucleotide probe length can
      impact the performance of a DNA microarray platform. RESULTS: We demonstrate
      solution-phase hybridization behavior of probe:target interactions by showing a
      strong correlation between the effect of mismatches in probes attached to a three
      dimensional matrix of a microarray and solution-based, thermodynamic duplex
      melting studies. The effects of mismatches in the probes attached to the
      microarray also demonstrate that most, if not all, of the
      oligodeoxyribonucleotide is available for hybridization. Kinetic parameters were
      also investigated. As anticipated, hybridization signals increased in a
      transcript concentration-dependent manner, and mismatch specificity increased
      with hybridization time. Unexpectedly, hybridization time increased the accuracy
      of fold changes by relieving the compression observed in expression ratios, and
      this effect may be more dramatic for larger fold changes. CONCLUSIONS: Taken
      together, these studies demonstrate that a three-dimensional surface may enable
      use of shorter oligodeoxyribonucleotide probes and that hybridization time may be
      critical in improving the accuracy of microarray data.

PMID- 12801426
TI  - Attitudes of healthcare workers in U.S. hospitals regarding smallpox vaccination.
AB  - BACKGROUND: The United States is implementing plans to immunize 500,000 hospital
      based healthcare workers against smallpox. Vaccination is voluntary, and it is
      unknown what factors drive vaccine acceptance. This study's aims were to estimate
      the proportion of workers willing to accept vaccination and to identify factors
      likely to influence their decisions. METHODS: The survey was conducted among
      physicians, nurses, and others working primarily in emergency departments or
      intensive care units at 21 acute-care hospitals in 10 states during the two weeks
      before the U.S. national immunization program for healthcare workers was
      announced in December 2002. Of the questionnaires distributed, 1,165 were
      returned, for a response rate of 81%. The data were analyzed by logistic
      regression and were adjusted for clustering within hospital and for different
      number of responses per hospital, using generalized linear mixed models and SAS's
      NLMIXED procedure. RESULTS: Sixty-one percent of respondents said they would
      definitely or probably be vaccinated, while 39% were undecided or inclined
      against it. Fifty-three percent rated the risk of a bioterrorist attack using
      smallpox in the United States in the next two years as either intermediate or
      high. Forty-seven percent did not feel well-informed about the risks and benefits
      of vaccination. Principal concerns were adverse reactions and the risk of
      transmitting vaccinia. In multivariate analysis, four variables were associated
      with willingness to be vaccinated: perceived risk of an attack, self-assessed
      knowledge about smallpox vaccination, self-assessed previous smallpox vaccination
      status, and gender. CONCLUSIONS: The success of smallpox vaccination efforts will
      ultimately depend on the relative weight in people's minds of the risk of vaccine
      adverse events compared with the risk of being exposed to the disease. Although
      more than half of the respondents thought the likelihood of a bioterrorist
      smallpox attack was intermediate or high, less than 10% of the group slated for
      vaccination has actually accepted it at this time. Unless new information about
      the threat of a smallpox attack becomes available, healthcare workers'
      perceptions of the vaccine's risks will likely continue to drive their ongoing
      decisions about smallpox vaccination.

PMID- 12801427
TI  - Restoring function after spinal cord injury.
AB  - BACKGROUND: By affecting young people during the most productive period of their
      lives, spinal cord injury is a devastating problem for modern society. A decade
      ago, treating SCI seemed frustrating and hopeless because of the tremendous
      morbidity and mortality, life-shattering impact, and limited therapeutic options
      associated with the condition. Today, however, an understanding of the underlying
      pathophysiological mechanisms, the development of neuroprotective interventions,
      and progress toward regenerative interventions are increasing hope for functional
      restoration. REVIEW SUMMARY: This study addresses the present understanding of
      SCI, including the etiology, pathophysiology, treatment, and scientific advances.
      The discussion of treatment options includes a critical review of high-dose
      methylprednisolone and GM-1 ganglioside therapy. The concept that limited
      rebuilding can provide a disproportionate improvement in quality of life is
      emphasized throughout. CONCLUSIONS: New surgical procedures, pharmacologic
      treatments, and functional neuromuscular stimulation methods have evolved over
      the last decades that can improve functional outcomes after spinal cord injury,
      but limiting secondary injury remains the primary goal. Tissue replacement
      strategies, including the use of embryonic stem cells, become an important tool
      and can restore function in animal models. Controlled clinical trials are now
      required to confirm these observations. The ultimate goal is to harness the
      body's own potential to replace lost central nervous system cells by activation
      of endogenous progenitor cell repair mechanisms.

PMID- 12801428
TI  - Classification and treatment of tardive syndromes.
AB  - BACKGROUND: Tardive syndromes are a group of delayed-onset abnormal involuntary
      movement disorders induced by a dopamine receptor blocking agent. There are
      several phenomenologically distinct types of TS. REVIEW SUMMARY: The term tardive
      dyskinesia has been used to refer to the TS that presents with rapid, repetitive,
      stereotypic movements mostly involving the oral, buccal, and lingual areas.
      Tardive dystonia can be focal, segmental, or generalized. It commonly affects the
      face and neck followed by the arms and trunk. It usually results in retrocollis
      when it involves the neck and trunk arching backwards when it involves the trunk.
      Tardive akathisia is characterized by a feeling of inner restlessness and
      jitteriness with an inability to sit or stand still. Other tardive syndromes
      include tardive tics, myoclonus, tremor, and withdrawal-emergent syndrome. It
      remains unclear whether tardive parkinsonism truly exists. The only way to
      prevent TS is to avoid its etiologic agents. Chronic use of dopamine receptor
      blocking agents should be limited as much as possible to patients with chronic
      psychoses. In general, for mild TS, reducing the neuroleptic dose, switching to
      an atypical agent, or discontinuing antipsychotic treatment altogether in the
      hope of facilitating remission is recommended. For moderate to severe TS,
      tetrabenazine or reserpine may be the most effective agent. Neuroleptics should
      be resumed to treat TD in the absence of active psychosis only as a last resort
      for persistent, disabling, and treatment-resistant TD. CONCLUSIONS: The severity
      of the TS and the absolute need for antipsychotic therapy often dictate the
      treatment approach for this disorder.

PMID- 12801429
TI  - An approach to chronic fatigue syndrome in adults.
AB  - BACKGROUND: The neurologist is often asked to evaluate patients with a chief
      complaint of fatigue. Many neurologists do not believe in the pathologically
      based disease known as chronic fatigue syndrome, yet as a group, neurologists are
      well suited to guide the diagnostic work up of such patients to pinpoint
      treatable disorders in the realm of neurology, general medicine, and psychiatry.
      REVIEW SUMMARY: Every patient should be carefully evaluated for certain medical,
      psychiatric, and neurologic disease that can cause fatigue as the most prominent
      symptom. This is most pressing because new work in virology, immunology, and
      imaging holds promise but still does not provide any diagnostic test or a
      mechanism for the production of these symptoms. Only a few treatments meet with
      even modest success in CFS. The goal of this paper is to provide the clinical
      neurologist with a framework for the investigation and management of this
      challenging group of patients. CONCLUSIONS: Neurologists are typically also
      trained in psychiatry and general medicine, and this is a strong position to
      evaluate the patient with fatigue. Because no presently available test can make
      the diagnosis of CFS, the assessment is vital to seek out more treatable
      illnesses.

PMID- 12801430
TI  - Association of internal carotid artery dissection and chiropractic manipulation.
AB  - BACKGROUND: To determine the relationship between chiropractic manipulative
      therapy and internal carotid artery dissection, a MEDLINE literature search was
      performed for the years 1966 through 2000 using the terms internal carotid
      dissection. Literature that included information concerning causation of ICAD, as
      well as all case studies and series, was selected for review. REVIEW SUMMARY: In
      reviewing the cases of internal carotid dissection potentially related to CMT,
      there were many confounding factors, such as connective tissue aberrations,
      underlying arteriopathy, or coexistent infection, that obscured any obvious cause
      and-effect relationship. To date there are only 13 reported cases of ICAD
      temporally related to CMT. Most ICADs seem to occur spontaneously and progress
      from local symptoms of headache and neck pain to cortical ischemic signs.
      Approximately one third of the reported cases were manipulated by practitioners
      other than chiropractic physicians, and because of the differential risk related
      to major differences in training and practice between practitioners who
      manipulate the spine, it would be inappropriate to compare adverse outcomes
      between practitioner groups. CONCLUSIONS: The medical literature does not support
      a clear causal relationship between CMT and ICAD. Reported cases are exceedingly
      scarce, and none support clear cause and effect.

PMID- 12801431
TI  - Mitochondriopathy mimicking amyotrophic lateral sclerosis.
AB  - BACKGROUND: Mitochondriopathy has been rarely reported to imitate motor neuron
      disease. REVIEW SUMMARY: A 57-year-old, 157-cm-tall woman with clinical and
      electrophysiological features of motor neuron disease since 1993 is reported. She
      also had increased liver function parameters, hypothyroidism, and sinus
      tachycardia. Because her mother and sister had both died from assumed amyotrophic
      lateral sclerosis, familial ALS was diagnosed. On reevaluation, screening for
      superoxide-dismutase gene mutations was negative, but lactate stress testing was
      abnormal and muscle biopsy revealed patchy COX deficiency and abnormal
      mitochondria. Analysis of the muscle mtDNA revealed substitutions in the
      isoleucine tRNA, in the ATPase-6, and in the cytochrome-b gene, respectively.
      Based on these data, the diagnosis of ALS was changed to mitochondriopathy.
      CONCLUSIONS: Mitochondriopathy may mimic ALS, phenotypically and
      electrophysiologically. In patients with an ALS phenotype, slow progression, and
      multisystem involvement, mitochondriopathy should be considered a diagnostic
      possibility.

PMID- 12801432
TI  - Ten most commonly asked questions about the psychiatric aspects of Parkinson's
      disease.

PMID- 12801433
TI  - Patient and family factsheet. Trigeminal neuralgia.

PMID- 12801434
TI  - Repetitive task practice: a critical review of constraint-induced movement
      therapy in stroke.
AB  - BACKGROUND: Constraint-induced (CI) movement therapy (also called forced use by
      some investigators and clinicians) has gained increasing popularity as a
      treatment mode for restoring function in the upper extremities of patients with
      stroke. The purpose of this article is to review the concept of constraint
      induced movement therapy and provide a critical analysis of the existing data.
      REVIEW SUMMARY: The evidence to date offers encouragement for the application of
      this procedure for patients who have some movement recovery out of synergy.
      Success may be contingent on patient cooperation and intense repetitive use with
      applications of retraining through practice and shaping. The extent to which each
      of the latter elements influences the magnitude of recovery is still unclear.
      However, task novelty and challenge seem important to recovery of function. There
      are several methods used to map cortical changes after stroke. At this time,
      transcranial magnetic stimulation is the primary vehicle used to assess motor
      cortical reorganization after CI therapy in humans. CONCLUSIONS: Accumulating
      data indicate that the size of a cortical area representative of a muscle does
      expand and its center of gravity does change with CI therapy.

PMID- 12801436
TI  - Gender issues in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is primarily a disease of premenopausal
      women. Interactions between the disease and the reproductive cycle are important
      to consider for optimal patient management. REVIEW SUMMARY: Sex hormones are
      potent immunomodulators, and their actions may help explain the gender
      distribution seen in MS and other immune-mediated diseases. Preliminary data
      suggest that immune function may vary cyclically as a function of hormonal
      milieu. MS does not affect fertility or the ability to bear children, and
      pregnancy generally has a salutary effect on the disease. Possible teratogenic
      actions of drugs used for symptom management and prophylactic treatment must be
      reviewed when managing patients. CONCLUSIONS: Additional studies are needed to
      delineate the roles of sex hormones as etiologic (and possibly therapeutic)
      agents in MS. Pharmacologic treatment of MS may impact reproductive function.
      Neurologists need to be familiar with these issues to assist their patients in
      choosing therapies and family planning.

PMID- 12801435
TI  - Current management of postherpetic neuralgia.
AB  - BACKGROUND: The herpes zoster rash occurs when a dormant varicella zoster virus
      reactivates in dorsal root and cranial nerve ganglia. Pain that persists in the
      region where this rash occurred after the cutaneous lesions have healed is termed
      postherpetic neuralgia (PHN). A wide variety of therapies has been used with
      varying degrees of success to prevent the occurrence of PHN and to reduce pain
      with established PHN. REVIEW SUMMARY: In this review, we discuss the clinical
      presentation of PHN, current strategies for the prevention and management of this
      disease, and observations that have increased our understanding of the neural
      mechanisms involved in PHN. CONCLUSIONS: Several classes of drugs are effective
      in attenuating the pain and hyperalgesia caused by PHN, but no single drug leads
      to the complete relief of symptoms. Additional research is needed to improve
      treatment strategies and define the role of invasive pain management techniques
      in cases where PHN is associated with intractable pain.

PMID- 12801437
TI  - Chiari type I malformation revisited: diagnosis and treatment.
AB  - BACKGROUND: Chiari type I malformations (Chiari I) are congenital deformities
      where caudal migration of the cerebellar tonsils through the foramen magnum
      compresses the cerebellum and cervicomedullary junction (lower brainstem and
      upper cervical spinal cord). Associations with chronic fatigue syndrome,
      fibromyalgia, orthostatic intolerance, and other neurologic syndromes have been
      proposed along with the current plethora of known symptoms of this disease
      process. In advanced cases, Chiari I malformations can lead to significant
      neurologic deficit and be the cause of permanent nervous system damage. REVIEW
      SUMMARY: This article focuses on the clinical diagnosis and treatment of patients
      with Chiari I, including a discussion on the possible mechanisms of Chiari I with
      a review of present diagnostic tests, indications for treatment, and appraisal of
      surgical outcome. CONCLUSIONS: Future radiological advances and research will
      undoubtedly be directed to better understanding of the pathology of the Chiari
      malformation and more effective medical and surgical treatment.

PMID- 12801439
TI  - Ten most commonly asked questions about headaches associated with spontaneous
      cerebrospinal fluid leaks... with one bonus question!

PMID- 12801438
TI  - Drug-induced parkinsonism.
AB  - BACKGROUND: Drug-induced parkinsonism is common but often unrecognized. In
      addition to neuroleptics, many medications of diverse chemical nature may induce
      or exacerbate parkinsonism REVIEW SUMMARY: Reports in the literature of drug
      induced parkinsonism or of an underlying parkinsonian disorder exacerbated by a
      medication were located using MEDLINE, and pertinent bibliographies were
      reviewed. The range of medications that may induce or exacerbate parkinsonism
      spans the medical specialties. Along with neuroleptics, selective-serotonin
      reuptake inhibitors, lithium, valproic acid, calcium channel blockers,
      antiarrhythmics, procholinergics, chemotherapeutics, amphotericin B, estrogens,
      and others have been implicated. CONCLUSIONS: This review seeks to enhance
      clinicians' knowledge of potential medications producing iatrogenic parkinsonism
      and encourage their vigilance in recognizing it.

PMID- 12801440
TI  - Rehabilitation after a stroke.

PMID- 12801441
TI  - Clinical implications of local renin-angiotensin-aldosterone systems.

PMID- 12801442
TI  - Optimal medical management of angina.
AB  - Coronary artery disease remains one of the principal causes of disability
      worldwide. Its most common manifestation is angina pectoris. Angina occurs due to
      an imbalance between myocardial oxygen demand and supply; it is classically
      precipitated by physical activity, emotion, eating, or cold weather. It is
      defined as stable when its frequency, severity, duration, time of appearance, and
      precipitating factors remain unchanged for 60 days. Treatment of patients with
      stable angina targets a number of factors that underlie its pathophysiology:
      aspirin as an antiplatelet agent, b-blockade to reduce myocardial oxygen demand,
      and additional antianginal drugs when symptoms are incompletely controlled by b
      blockers alone. Furthermore, aggressive treatment of risk factors for the
      development of coronary artery disease confers a significant mortality benefit.
      Unstable angina is defined as symptoms developing at rest, on minimal exertion,
      and of increasing severity, duration, or frequency. It is associated with
      significant mortality; consequently, early assessment and intervention is
      essential to prevent worsening ischemia. Treatment includes close in-patient
      monitoring, administration of antiplatelet and antithrombotic drugs, and a
      combination of b-blockers, calcium antagonists, and intravenous nitrates where
      appropriate. Coronary revascularization should be considered in high-risk
      patients, and when conservative management strategies fail.

PMID- 12801443
TI  - Acute coronary syndromes in patients with renal failure.
AB  - As the rates of obesity and diabetes continue to rise sharply in the United
      States, there is a secondary epidemic of diabetic nephropathy, chronic kidney
      disease, and end-stage renal disease requiring renal replacement therapy.
      Cardiovascular disease is the leading cause of death in patients with renal
      disease. Many sources of information support the concept that the metabolic
      condition caused by renal failure is an independent cardiac risk factor with a
      direct relationship to the pathogenesis of atherosclerosis, acute coronary
      syndromes (ACS), heart failure, and arrhythmias. An estimated glomerular
      filtration rate less than 60 mL/min/1.73 m(2) has consistently been shown to be
      the most powerful predictor of adverse outcomes in ACS. This paper focuses on ACS
      and highlights the major issues with respect to diagnosis and treatment in
      patients with underlying renal failure. Because patients with renal disease are
      routinely excluded from clinical trials of ACS, we draw upon a variety of
      clinical data sets to gather an evidenced-based approach to this important and
      growing population of patients.

PMID- 12801444
TI  - B-type natriuretic peptide in ischemic heart disease.
AB  - B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N
      proBNP) are released from the heart in response to increased wall stress. Assays
      for these peptides are now commercially available, and measurement of BNP and N
      proBNP is becoming commonplace in patients with suspected heart failure. BNP and
      N-proBNP facilitate diagnosis and risk stratification in patients with heart
      failure, and may help guide response to therapy. This review focuses on the
      emerging role of BNP and N-proBNP measurement in patients with acute coronary
      syndromes (ACS). Although experimental studies demonstrate rapid BNP release in
      response to cardiac ischemia, it is unlikely that BNP will be used to diagnose
      cardiac ischemia, because many other conditions are also associated with modest
      BNP elevation. In contrast, BNP holds tremendous promise as a prognostic marker
      in patients with ACS. Studies to date have shown consistently that higher BNP
      levels are associated with worse clinical outcomes, and that BNP provides unique
      information to clinical variables, other biomarkers, and left ventricular
      ejection fraction. Future studies are needed to identify the therapeutic
      implications of BNP elevation in patients with ACS.

PMID- 12801445
TI  - ST-segment monitoring in patients with acute coronary syndromes.
AB  - ST-segment analyses from electrocardiograms during acute coronary syndromes (ACS)
      have repeatedly shown strong mechanistic links to coronary artery patency and
      myocardial reperfusion. In these patients, such analyses have also consistently
      been reported to have close correlations with outcome--correlations superior even
      to those reported for invasive coronary flow measurements and outcome. Continuous
      multilead ST-monitoring of patients with ACS provides accurate and noninvasive
      information on the dynamics of the myocardial reperfusion process over time. This
      information can be used for improved early diagnostic accuracy, evaluation of
      treatment efficacy, early risk-stratification, and can be supportive in clinical
      decision making regarding these patients. Continuous multilead ST-monitoring
      during ACS is no longer a cumbersome source of more nuisance than benefit, but
      can be an accurate and useful tool in multicenter clinical trials, as well as in
      clinical medicine.

PMID- 12801448
TI  - Revised guidelines for the management of non-ST-segment elevation acute coronary
      syndromes.
AB  - Unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI)
      refer to a spectrum of acute severe cardiac disorders characterized by myocardial
      oxygen demand and supply mismatch, caused by atherosclerotic coronary artery
      disease. Patients presenting with acute coronary syndromes represent a major
      medical problem, accounting for 2.5 million hospitalizations and 500000 deaths
      annually in the United States alone. Of these, 1.5 million have a final diagnosis
      of UA, and myocardial infarction (ST-segment and non-ST-segment elevation)
      accounts for the remaining 1 million. The management of UA/NSTEMI presents a
      challenge to the cardiologist because treatment strategies continue to evolve. A
      number of trials have now assessed the safety and efficacy of early
      revascularization strategies in the treatment of patients with UA/NSTEMI, whereas
      others have focused on pharmacologic adjunctive therapy. An optimal single
      strategy encompassing most patients' needs is not clear. This review focuses on
      the revised American College of Cardiology/American Heart Association guidelines
      for the management of patients presenting with UA/NSTEMI.

PMID- 12801449
TI  - Acute coronary syndromes in patients with diabetes mellitus: diagnosis,
      prognosis, and current management strategies.
AB  - The incidence of type-2 diabetes mellitus is rising rapidly both in the United
      States and worldwide. Because of its presence in so many patients with acute
      coronary syndromes, it is becoming essential for cardiologists to understand the
      basic pathophysiology of insulin resistance, its role in the development of type
      2 diabetes, and its association with accelerated atherosclerosis. Because
      diabetes imparts a worse prognosis among patients with acute coronary syndromes,
      these patients warrant aggressive antiplatelet and antithrombotic therapy, as
      well as a more invasive management strategy.

PMID- 12801450
TI  - Dosing considerations and monitoring of low molecular weight heparins and
      glycoprotein IIb/IIIa antagonists in patients with renal insufficiency.
AB  - Glycoprotein IIb/IIIa inhibitors and low molecular heparins are important new
      components of the medical treatment for acute coronary syndromes (ACS). Renal
      insufficiency is a common comorbid condition and high-risk marker for ACS. The
      safety and efficacy of these treatments in ACS are dependent on the
      pharmacokinetics of the specific medication. Even though these treatments have
      been studied in large randomized controlled trials in ACS, there are few
      prospective data regarding their safety or efficacy in renal insufficiency. Most
      have been shown to be safe and effective in mild to moderate degrees of renal
      insufficiency; none have been thoroughly studied in severe renal disease or in
      patients requiring dialysis therapy. Future prospective trials should include
      patients with more severe renal insufficiency, as well as combinations of the
      current recommended therapies.

PMID- 12801451
TI  - Emergency management of hemorrhagic complications in the era of glycoprotein
      IIb/IIIa receptor antagonists, clopidogrel, low molecular weight heparin, and
      third-generation fibrinolytic agents.
AB  - Antithrombotic, antiplatelet, and fibrinolytic agents are the mainstay for the
      management of patients with acute coronary syndromes (ACS). In addition to their
      well-documented efficacy, these pharmacologic agents have the potential for the
      untoward effect of bleeding. Recent data suggest medication errors related to the
      dose, duration, and concomitant use of these agents contribute to increasing the
      risk of hemorrhage in patients treated for ACS. In the event of a major
      hemorrhage, clinicians should be aware of strategies used to reverse the
      pharmacologic effects of the offending agent. This paper critically assesses
      literature directed toward reversal of agents based on drug-specific
      pharmacodynamic and pharmacokinetic parameters.

PMID- 12801454
TI  - When to order cardiovascular magnetic resonance in adults with congenital heart
      disease.
AB  - Cardiovascular magnetic resonance (CMR), where available, contributes to the
      informed management of patients with congenital heart disease. In contrast to
      echocardiography, CMR becomes easier as patients grow. It is versatile and gives
      unrestricted access to the heart and intrathoracic vessels, providing functional
      and structural information. Its relative strengths are discussed, and examples
      are given of congenital conditions in which it provides clinically important
      information. CMR can prevent the need for diagnostic catheterization or expedite
      intervention if indicated, enabling planned, directed procedures. In our
      practice, CMR is used for serial follow-up, investigation of altered symptoms or
      signs, planning of transcatheter or surgical interventions, and for baseline
      assessment after surgery. As CMR becomes more widely available, it will
      contribute increasingly to the lifelong management of patients with congenital
      heart disease.

PMID- 12801455
TI  - Detecting and diagnosing arrhythmias in adults with congenital heart disease.
AB  - Arrhythmias are a major cause of morbidity and mortality in adults with
      congenital heart disease; they can range from occult asymptomatic sinus node
      disease to sudden death. Detecting and diagnosing these arrhythmias presents a
      challenge when caring for these patients. A high index of suspicion is necessary,
      as well as a thorough understanding of the underlying heart defect and subsequent
      surgical interventions. A careful history, noninvasive evaluation, and in some
      cases invasive testing are all necessary to determine arrhythmias in this
      population.

PMID- 12801456
TI  - In vitro susceptibilities of field isolates of Mycoplasma agalactiae to
      oxytetracycline, tylosin, enrofloxacin, spiramycin and lincomycin-spectinomycin.
AB  - The minimum inhibitory concentrations (MICs) of tetracycline, enrofloxacin,
      tylosin, spiramycin and a lincomycin:spectinomycin 1:2 combination, against 24
      Sicilian isolates of Mycoplasma agalactiae, the causative organism of contagious
      agalactia were determined in vitro by a broth dilution method. Enrofloxacin was
      the most effective antimicrobial in vitro with a range of MIC values from 0.125
      to 0.500 microg/ml and an MIC(50) of 0.203 and MIC(90) of 0.365 microg/ml. Using
      the MIC(50) and MIC(90) values the remaining four antimicrobials are ranked in
      order of in vitro effectiveness as follows: tylosin (MIC(50)0.292; MIC(90)0.525
      microg/ml) was slightly more effective than tetracycline (MIC(50)0.296;
      MIC(90)0.533 microg/ml), followed by lincomycin:spectinomycin (MIC(50)0.521;
      MIC(90)0.938 microg/ml) and spiramycin (MIC(50)1.583; MIC(90)2.850 microg/ml).
      MIC values above 1.000 microg/ml were obtained using tetracycline, tylosin and
      spiramycin for some M. agalactiae isolates.

PMID- 12801457
TI  - Effects of probiotics: alone and in a mixture of Biosacc plus Zinc Bacitracin on
      the caecal microflora of Japanese quail.
AB  - The aim of this study was to investigate the effects of two commercially
      available probiotics, alone and in combination with an antibiotic, on the caecal
      flora of Japanese quail (Coturnix coturnix japonica) reared under unstressed
      conditions. Thirty-four 90-day-old Japanese quail were selected for this study.
      The birds were divided into four groups, two groups of nine birds and two groups
      of eight birds. The animals in these groups were given feed containing 0.5 kg per
      tonne of probiotics alone (Protexin or Biosacc), a mixture of probiotic plus
      antibiotic (Biosacc plus Zinc Bacitracin at 0.5 and 0.0525 ppm, respectively),
      and a group where no supplement was added to be used as controls. The total count
      of aerobic bacteria, lactobacilli, enterobacteriaceae, coliforms, enteroccoci,
      salmonellae, sulphite-reducing anaerobic bacteria (clostridia), and pH values in
      the caecal content of the birds were examined. No significant differences were
      detected among the four groups for pH values and bacterial number (p>0.05),
      except for sulphite-reducing anaerobic bacteria (p<0.001). These results suggest
      that the use of probiotics alone and/or a mixture of a probiotic plus antibiotic
      as a feed supplement does not have a major suppressing effect on the majority of
      bacterial groups in the caecal flora of mature, healthy Japanese quail reared in
      unstressed conditions.

PMID- 12801458
TI  - Activities of enzymes in the malate-aspartate shuttle and the isoenzyme pattern
      of lactate dehydrogenase in plasma and peripheral leukocytes of lactating
      Holstein cows and riding horses.
AB  - The activities of the enzymes involved in the malate-aspartate shuttle and
      lactate dehydrogenase (LDH) and the pattern of the isoenzymes of LDH were
      determined in plasma and peripheral leukocytes of lactating Holstein cows and
      thoroughbred riding horses as representative herbivorous animals. In the horse
      plasma, LDH activities were significantly lower and AST activities were
      significantly higher than those in the cow plasma. The specific activities of
      cytosolic malate dehydrogenase (MDH), LDH and AST in the horse leukocytes were
      higher than those in the cows. The cytosolic ratio of MDH/LDH activity (ML ratio)
      in the horse leukocytes was significantly lower than that in the cow leukocytes
      owing to significantly higher activities of LDH. The ML ratio was considered to
      reflect the difference in energy metabolism in leukocytes between cows and
      horses. The plasma LDH isoenzyme patterns of cow and horse showed the
      characteristic as herbivorous animals with dominance of LDH-1, -2 and -3. The LDH
      isoenzyme patterns with dominance of LDH-3 and -4 in the horse leukocytes were
      remarkably different from those in the cow leukocytes. There were significant
      differences in activities of malate-aspartate shuttle enzymes, ML ratio and LDH
      isoenzyme patterns in the cytosolic fractions of leukocytes between the lactating
      cows and the riding horses.

PMID- 12801459
TI  - Health status of a population of nutria (Myocastor coypus) living in a protected
      area in Italy.
AB  - Ninety trapped nutria (Myocastor coypus) from a protected area of Piedmont
      (Italy), including the Po river, were examined for the prevalence for lesions in
      major viscera, selected serum antibodies and enteric bacteria. Coccidial lesions
      in the liver included cholangitis, calcification and necrosis. Renal lesions were
      nonsuppurative interstitial nephritis and a single case of renal adenocarcinoma.
      The lungs had a 41.1% prevalence of nonsuppurative interstitial pneumonia. Ten of
      87 sera (11.5%) had antibodies against Leptospira bratislava, 3 of 87 (3.4%)
      against Leptospira ichterohaemorrhagiae, 15 of 41 (36.6%) against Toxoplasma
      gondii, and antibodies against encephalomyocarditis virus were detected in 5 of
      78 sera (6.4%). All fecal samples were negative for Salmonella, Shigella, and
      Pseudomonas, and growth of enterobacteriaceae was in the normal range.

PMID- 12801460
TI  - Effects of extracellular Ca2+ on phagocytosis and intracellular Ca2+
      concentrations in polymorphonuclear leukocytes of postpartum dairy cows.
AB  - The aim of this study was to determine the effects of extracellular Ca(2+)
      concentration ([Ca(2+)](e)) on phagocytosis and intracellular Ca(2+)
      concentration ([Ca(2+)](i)) in bovine polymorphonuclear leukocytes (PMNs). The
      experiments were performed by using blood samples from parturient paretic and
      clinically normal parturient cows and manipulating the [Ca(2+)](e) in vitro.
      Phagocytosis by PMNs (with and without stimulation with phorbol myristate acetate
      and inhibition with cytochalasin B) and resting [Ca(2+)](i) were significantly
      lower in parturient paretic cows. Repletion of Ca(2+) in the extracellular media
      for the samples from these animals increased phagocytosis and resting
      [Ca(2+)](i). In the blood of clinically normal parturient cows, decreasing the
      [Ca(2+)](e) decreased phagocytosis and resting [Ca(2+)](i) in PMNs, but
      increasing the [Ca(2+)](e) did not affect phagocytosis. These results suggest
      that the hypocalcemic condition of parturient paretic cows in vivo causes
      decreased phagocytosis and resting [Ca(2+)](i) in PMNs, which may partly
      contribute to greater susceptibility to infection.

PMID- 12801461
TI  - The relative effects of supplemental dietary calcium and oxalate on urine
      composition and calcium oxalate relative supersaturation in healthy adult dogs.
AB  - The aim of this study was to establish the relative effects of dietary calcium
      and oxalate (in the form of oxalic acid) on the composition of urine produced by
      healthy adult Cairn Terriers and Miniature Schnauzers. A nutritionally complete
      dry dog food was fed to 7 dogs (4 Cairn terriers and 3 Miniature schnauzers) for
      24 weeks. The dogs were fed the diet alone, or supplemented with six different
      combinations of dietary calcium (as carbonate and sulphate) and oxalate (as
      oxalic acid) commonly found in dry commercially prepared dog foods. Urine pH,
      volume, specific gravity, and concentrations of 12 analytes were measured for
      each dog; urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was
      calculated from these values. The effects of supplemental calcium and oxalate
      were established using two-way analysis of variance and multiple range tests
      (least significant difference); P<0.05 was considered significant. The lowest
      level of dietary calcium and oxalate resulted in the lowest CaOx RSS. The high
      calcium, low oxalate diet resulted in the highest CaOx RSS, a low calcium diet
      with increased dietary oxalate also tended to increase CaOx RSS although results
      were highly variable. Urinary calcium concentration increased significantly with
      dietary calcium; urinary oxalate increased, although inconsistently, with dietary
      oxalic acid only when dietary calcium was low. Measures to reduce both calcium
      and oxalate should be considered when implementing dietary changes to reduce the
      risk of calcium oxalate formation in dogs. A reduction in dietary calcium without
      a concomitant decrease in dietary oxalate may increase the risk of CaOx
      crystallisation in susceptible dogs.

PMID- 12801462
TI  - Hypertrophy of intestinal smooth muscle in cats.
AB  - Pathological findings of four cats with severe and diffuse smooth muscle
      hypertrophy of the small intestine (MHSI) are reported and compared to those of
      five cats with segmental MHSI secondary to neoplastic obstruction and four
      controls. Histology demonstrated a constant association between idiopathic MHSI
      and submucosal fibrosis and chronic lymphoplasmacytic enteritis. Morphometry (gut
      diameter, thickness and area of muscular layers, number and density of smooth
      muscle nuclei) and MIB-1-immunolabelling showed that the thickness increase was
      mostly due to hypertrophy, but hyperplasia was also evident. Microbiology from
      ileal content samples was performed in two cats with primary MHSI, and
      Campylobacter spp. were isolated, which were also demonstrated by
      immunohistochemistry and ultrastructure. The association of chronic enteritis
      with idiopathic MHSI suggests that factors released in intestinal inflammation
      may also act as hypertrophy stimuli for smooth muscle cells.

PMID- 12801463
TI  - Pharmacokinetics of oestriol after repeated oral administration to dogs.
AB  - The aim of the present study was to investigate the pharmacokinetics of oestriol
      in plasma in the dog after repeated oral administration of oestriol tablets, a
      preparation intended for the treatment of urinary incontinence in the bitch. The
      study was performed in six healthy, entire, adult female beagle dogs. The bitches
      were treated once daily with two tablets, containing 1 mg oestriol per tablet,
      for seven consecutive days (days 1-7). Blood samples were taken from the jugular
      vein before treatment, frequently on days 1, 3 and 7 of the treatment period and
      daily just before (C(trough)) and 1 h after dosing (C(t=1h)). During the washout
      period samples were taken at a 24 h interval up to four days post-treatment.
      Oestriol concentrations were determined in plasma by radioimmunoassay.
      Pharmacokinetic parameters, AUC, C(max) and t(max), were determined from the
      plasma concentration-time curves using non-compartmental methods. The between
      animal variation in C(max) and the AUC was high. Individual values of the C(max)
      varied from 206 pg/ml (day 1) to 1128 pg/ml (day 7) and the AUC(0-24h) from 789
      pg x h/ml (day 1) to 5718 pg x h/ml (day 7). t(max) occurred within 1 h. The mean
      C(trough) value was slightly above the pre-treatment level ( 38+/-2 pg/ml vs.
      18+/-5 pg/ml). Within 48 h after the last treatment the concentrations had
      returned to the pre-treatment values. C(max) and C(trough) did not increase
      during the treatment period, indicating that no accumulation occurred. A shoulder
      in the concentration-time curve around 8-12 h after treatment strongly suggested
      the existence of enterohepatic recirculation (EHR). The average relative
      contribution of the EHR to the AUC(0-24h) was estimated to be 22%, 38% and 44% on
      days 1, 3 and 7, respectively. These mean values were calculated from five
      animals per time point, because one dog failed to show EHR on days 1 and 3 and
      was therefore excluded from the calculations.

PMID- 12801464
TI  - The effects of benzimidazole anthelmintics on P4501A in rat hepatocytes and HepG2
      cells.
AB  - Benzimidazole anthelmintics including albendazole, fenbendazole, and mebendazole
      are widely used in veterinary medicine. The effects of these benzimidazoles on
      cytochrome P4501A were investigated in primary cultures of rat hepatocytes and in
      the HepG2 cell line. After incubation of rat hepatocytes and HepG2 for 24-, 48-,
      and 72-h cells with drugs at various concentrations (0.1-50 microM), the enzyme
      activities associated with P4501A1/2 (7-ethoxyresorufin O-deethylation and 7
      methoxyresorufin O-demethylation) were measured. The P4501A1/2 protein levels in
      both model systems were determined by Western blotting. Although all
      benzimidazoles provoked a significant increase of P4501A1/2 protein levels and
      P4501A activities, large differences in the induction response were found which
      was dependent on drug structure, concentration, and model system used. Based on
      the results, relationships between induction potency and structure of drug were
      demonstrated, as well as differences between the in vitro systems used.
      Therefore, pharmacological and toxicological consequences of cytochrome P4501A
      induction by benzimidazole drugs should be taken into account in veterinary
      therapy.

PMID- 12801465
TI  - Respiratory mechanics in conscious swine: effects of face mask, head position and
      bronchoconstriction evaluated by impulse oscillometry.
AB  - Airway obstruction in pigs (sedated or non-sedated) fixed in a sling was studied
      using impulse oscillometry (IOS). (i) Vertical flexion of the pig's head was used
      to simulate an artificial obstruction of the upper airways. (ii) Bronchial
      obstruction was induced by inhaling differing quantities of an aerosol produced
      from 0.33% carbachol solution. The ventilatory pattern was examined by measuring
      respiratory rate (RR) and tidal volume (V(t)). To evaluate respiratory mechanics,
      impedance parameters resistance (R) and reactance (X) as well as coherence (Co)
      were examined, each at frequencies of 5, 10, 15, 20, 25 and 35 Hz. Using a simple
      7-element-model introduced by J. Mead [Physiological Review 41 (1961) 281],
      distal respiratory resistance (R(dist)), proximal airway resistance (R(prox)),
      and additional shunt compliance (C(a)) of the animal's snout and the air inside
      the facemask were evaluated. By fitting this model to the primary measured
      impedance spectra, the influence of the face mask could be eliminated in the
      model calculation to allow assessment of the real respiratory impedance. This
      recalculation made clear that the facemask had an influence on the spectral
      course of R and X, depending on the clinical situation, and the upper frequency
      range was altered the most. Under conditions of (i) upper airway obstruction,
      especially the X values were distorted by facemask almost over the whole
      frequency range. Once the data were corrected for the mask, resistance was
      increased across all frequencies by a fixed amount while reactance was not
      affected. Under (ii) bronchial airway obstruction (bronchospasm) caused the
      resistance spectrum to be increased mainly in the lower frequency range. This
      became visible in both, originally measured impedance spectra and spectra after
      correction of the mask influence. The reactance course (originally measured and
      recalculated) decreased at all frequencies during bronchospasm. Coherence over
      the whole frequency range was lowered at both bronchial and upper airway
      obstruction.

PMID- 12801466
TI  - In vitro characterisation of high and low virulence isolates of equine
      herpesvirus-1 and -4.
AB  - Basic in vitro characteristics of high and low virulence isolates of equine
      herpesviruses-1 and -4 were investigated with particular reference made to the
      Ab4 and V592 isolates of EHV-1 as both have distinct endotheliotropism and
      clinical outcomes in pony challenge studies. Additionally, some EHV-4 isolates
      that showed variations in clinical outcome were included in some experiments. The
      aim of the study was to identify an in vitro characteristic that would
      differentiate strains of known virulence. Such a system could then be applied to
      vaccine and virulence studies as an effective screening tool. Viral growth
      kinetics in a variety of cell culture systems, plaque size, ability to replicate
      in fetal endothelium in organ culture, and sensitivity to acyclovir were
      compared. No reliable marker system that differentiated between higher and lower
      virulence isolates of EHV-1 and EHV-4 was identified.

PMID- 12801467
TI  - Molecular systematics of the North American freshwater bivalve genus Quadrula
      (Unionidae: Ambleminae) based on mitochondrial ND1 sequences.
AB  - A molecular phylogeny of the bivalve genus Quadrula (Unionidae) was constructed
      based on nucleotide sequences of the mitochondrial ND1 gene. Phylogenetic
      analysis of 66 specimens representing 17 of the 20 currently recognized taxa
      within Quadrula, three closely allied species, and 16 outgroup taxa reveals a non
      monophyletic Quadrula due to the placement of Tritogonia verrucosa, 'Fusconaia'
      succissa, and 'Quincuncina' infucata. We suggest that the taxonomic description
      of the genus Quadrula be expanded to include these species. Within the genus, we
      continue to recognize three monophyletic species groups (the quadrula, metanvera,
      and pustulosa species groups), as historically described; however, the pustulosa
      species group must include 'F.' succissa and 'Quincuncina' infucata. Finally,
      while our findings place the monotypic genus Tritogonia within Quadrula, its
      relationship to members within the genus Quadrula remains unresolved.

PMID- 12801468
TI  - Phylogenetic relationships of Pelobatoidea re-examined using mtDNA.
AB  - Pelobatoidea is a clade of ancient anurans with obscure relationships to the
      remaining clades of frogs. We used partial sequences of two mitochondrial genes
      (cytochrome b and 16S RNA) from all Pelobatoidea subclades, including all species
      of Pelobatidae and Pelodytidae and four outgroup taxa (Xenopus, Ascaphus,
      Discoglossus, and Rana), to propose a phylogenetic hypothesis for relationships
      within Pelobatoidea. Maximum likelihood and Bayesian analyses support the
      monophyly of Pelobatoidea, but our hypothesis of internal relationships differs
      substantially from all previous hypotheses. Megophryidae is sister to Pelobates,
      and this clade is sister to Pelodytes. The most basal clade within Pelobatoidea
      is formed by Scaphiopus and Spea. The family Pelobatidae, as previously defined
      is not monophyletic, and it is split into Eurasian spadefoot toads Pelobates
      which retain the name Pelobatidae and North American spadefoot toads Scaphiopus
      and Spea which comprise the revived taxon Scaphiopodidae. Our analysis uncovers
      the existence of morphologically cryptic taxa within previously recognized
      species of the genus Spea and reveals marked genetic differentiation within
      Iberian Pelodytes. We discuss biogeographic implications and the evolution of
      fossoriality in the light of the new phylogenetic hypothesis.

PMID- 12801470
TI  - Molecular phylogeny and biogeography of the wall-lizard Podarcis erhardii
      (Squamata: Lacertidae).
AB  - Erhard's wall lizard, Podarcis erhardii (Sauria: Lacertidae), is highly
      diversified in Greece and especially in the southern Aegean region. Out of the 28
      recognized subspecies, 27 are found in Greece from the North Sporades island
      complex in the North Aegean (grossly south of the 39th parallel) to the island of
      Crete in the South. The species exhibits great morphological and ecological
      plasticity and inhabits many different habitats from rocky islets and sandy
      shores to mountaintops as high as 2000m. By examining intraspecific variability
      at a segment of the mitochondrial gene cytochrome b we have found that that
      extant populations of P. erhardii are paraphyletic. Furthermore, we have found
      that subspecies previously defined on the basis of morphological characteristics
      do not correspond to different molecular phylogenetic clades, so that their
      status should be reconsidered. The DNA based biogeographical and phylogenetic
      history of Podarcis in Southern Greece is congruent with available
      paleogeographic data of the region, which supports the view that DNA sequences
      may be a useful tool for the study of palaeogeography.

PMID- 12801469
TI  - Patterns of diversification in two African forest shrews: Sylvisorex johnstoni
      and Sylvisorex ollula (Soricidae, Insectivora) in relation to paleo-environmental
      changes.
AB  - We analysed the phylogeographic patterns of two congeneric and syntopic species
      of forest shrews and compared them with biogeographical scenarios proposed for
      the Central African tropical forest. Our results, based on 82 partial 16s rRNA
      mitochondrial sequences, suggest that both species must have originated in the
      Plio-Pleistocene and that their haplotype distributions could reflect the effect
      of forest fragmentation and expansion associated with paleoclimatic fluctuations
      during the Pleistocene. However, it seems that the two species responded very
      differently to environmental changes. While Sylvisorex johnstoni populations
      exhibit ancient haplotype segregation that may even represent currently
      unrecognised allopatric species, Sylvisorex ollula haplotypes are much less
      differentiated and suggest that this taxon has undergone a recent range
      expansion. The observed differences between these taxa may be explained by their
      presumably different ecological requirements and colonisation abilities, which in
      turn may be the result of a significant difference in body size between the two
      species. In conclusion, our results suggest that it is necessary to incorporate
      several ecologically well-documented species in studies that attempt to infer
      evolutionary processes from phylogeographic patterns

PMID- 12801471
TI  - Using matK sequence data to unravel the phylogeny of Casuarinaceae.
AB  - Casuarinaceae are a Gondwanic family with a unique combination of morphological
      characters not comparable to any other family. Until recently, the 96 species in
      the family were classified in a single genus, Casuarina s.l. A recent
      morphological revision of the family resulted in the splitting of Casuarina s.l.
      into four genera-Allocasuarina, Casuarina s.s., Ceuthostoma, and Gymnostoma. This
      study uses matK sequence data from 76 species of Casuarinaceae and eight outgroup
      taxa to examine the phylogenetic structure within the Casuarinaceae. The study
      demonstrates the monophyly of the four genera and examines the relationships
      within the family; it tests the validity of the infra-generic subdivision of
      Allocasuarina; it discovers geography-based infra-generic subdivisions within
      Gymnostoma and Casuarina; and, finally, provides a molecular framework on which
      to trace the evolution of xeromorphy in the Casuarinaceae.

PMID- 12801472
TI  - A molecular phylogeny of the Littorininae (Gastropoda: Littorinidae): unequal
      evolutionary rates, morphological parallelism, and biogeography of the Southern
      Ocean.
AB  - A molecular phylogeny is presented for the subfamily Littorininae (including
      representatives of all subgeneric taxa and all members of a group of southern
      temperate species formerly classified as 'Nodilittorina'), based on sequence data
      from two nuclear (18S rRNA, 28S rRNA) and two mitochondrial (12S rRNA, CO1)
      genes. The phylogeny shows considerable disagreement with earlier hypotheses
      derived from morphological data. In particular, 'Nodilittorina' is polyphyletic
      and is here divided into four genera (Echinolittorina, Austrolittorina,
      Afrolittorina new genus, and the monotypic Nodilittorina s.s.). The phylogenetic
      relationships of 'Littorina' striata have been controversial and it is here
      transferred to the genus Tectarius, a surprising relationship for which there is
      little morphological support. The relationships of the enigmatic Mainwaringia
      remain poorly resolved, but it is not a basal member of the subfamily. The two
      living species of Mainwaringia are remarkable for a greatly elevated rate of
      evolution in all four genes examined; it is suggested that this may be connected
      with their protandrous hermaphroditism, which is unique in the family. The
      molecular phylogeny provides a new framework for the adaptive radiation of the
      Littorininae, showing more frequent shifts between habitats and climatic regimes
      than previously suspected, and striking parallelism of morphological characters.
      The fossil record of littorinids is poor, but ages of clades are estimated using
      a calibration based on a Lower Eocene age of the genus Littoraria. Using these
      estimates, the antitropical distribution of Littorina and Afrolittorina is an
      ancient pattern of possibly Cretaceous age. The five members of Austrolittorina
      show a Gondwanan distribution in Australia, New Zealand, and South America. Based
      on the morphological uniformity within this clade, relatively recent (Plio
      Pleistocene) trans-Pacific dispersal events seemed a likely explanation, as
      proposed for numerous other congeneric marine taxa. However, molecular estimation
      of ages of divergence suggest an initial vicariance between Australian and South
      American lineages at 40-73Ma, contemporary with the later stages of fragmentation
      of the Gondwanan supercontinent, followed by more recent (but still mid-Cenozoic)
      dispersal events across the Tasman Sea and the Pacific Ocean. Afrolittorina is
      another Cretaceous clade, now restricted to southern Africa and southern
      Australia, but divergence between these lineages (29-55Ma) post-dates Gondwanan
      fragmentation. Within both Austrolittorina and Afrolittorina all sister-species
      divergences are estimated to fall in the range 10-47Ma, so that there is no
      evidence for speciation events in the Plio-Pleistocene.

PMID- 12801473
TI  - Mitochondrial DNA, morphology, and the phylogenetic relationships of Antarctic
      icefishes (Notothenioidei: Channichthyidae).
AB  - The Channichthyidae is a lineage of 16 species in the Notothenioidei, a clade of
      fishes that dominate Antarctic near-shore marine ecosystems with respect to both
      diversity and biomass. Among four published studies investigating channichthyid
      phylogeny, no two have produced the same tree topology, and no published study
      has investigated the degree of phylogenetic incongruence between existing
      molecular and morphological datasets. In this investigation we present an
      analysis of channichthyid phylogeny using complete gene sequences from two
      mitochondrial genes (ND2 and 16S) sampled from all recognized species in the
      clade. In addition, we have scored all 58 unique morphological characters used in
      three previous analyses of channichthyid phylogenetic relationships. Data
      partitions were analyzed separately to assess the amount of phylogenetic
      resolution provided by each dataset, and phylogenetic incongruence among data
      partitions was investigated using incongruence length difference (ILD) tests. We
      utilized a parsimony-based version of the Shimodaira-Hasegawa test to determine
      if alternative tree topologies are significantly different from trees resulting
      from maximum parsimony analysis of the combined partition dataset. Our results
      demonstrate that the greatest phylogenetic resolution is achieved when all
      molecular and morphological data partitions are combined into a single maximum
      parsimony analysis. Also, marginal to insignificant incongruence was detected
      among data partitions using the ILD. Maximum parsimony analysis of all data
      partitions combined results in a single tree, and is a unique hypothesis of
      phylogenetic relationships in the Channichthyidae. In particular, this hypothesis
      resolves the phylogenetic relationships of at least two species (Channichthys
      rhinoceratus and Chaenocephalus aceratus), for which there was no consensus among
      the previous phylogenetic hypotheses. The combined data partition dataset
      provides substantial statistical power to discriminate among alternative
      hypotheses of channichthyid relationships. These findings suggest the optimal
      strategy for investigating the phylogenetic relationships of channichthyids is
      one that uses all available phylogenetic data in analyses of combined data
      partitions.

PMID- 12801475
TI  - The phylogeographic importance of the Strait of Gibraltar as a gene flow barrier
      in terrestrial arthropods: a case study with the scorpion Buthus occitanus as
      model organism.
AB  - The phylogenetic relationship between Buthus occitanus populations across the
      Strait of Gibraltar was investigated using nuclear 18S/ITS-1 DNA sequences and
      mitochondrial 16S and COI DNA sequences. All analyses showed that the European
      samples are highly separated from North African samples, and also suggest the
      existence of three main groups within this species complex, i.e., an European, an
      Atlas (=Moroccan samples) and a Tell-Atlas group (=Tunisian samples). The
      European clade was subdivided into three distinct subclades. The application of a
      previous calibration of the molecular clock of another buthid species suggested
      that most of the detected mitochondrial DNA lineages including the European
      lineages are about three times older than the re-opening of the Gibraltar Strait,
      and consequently, that other and older vicariant events are responsible for the
      observed phylogeographic structure of this species complex. Concerning the
      Moroccan samples, a discordance between nuclear and mitochondrial gene markers
      was observed. The 18S/ITS-1 gene tree could not resolve the phylogenetic
      relationships among the Moroccan B. occitanus subspecies and the closely related
      species B. atlantis, whereas mitochondrial genes suggested the co-existence of
      several old phylogenetic lineages in Morocco. We hypothesized that this
      difference may be explained by male-biased gene flow and gene conversion at the
      tandemly repeated 18S/ITS-1 gene regions.

PMID- 12801474
TI  - Phylogeny and evolution of developmental mode in temnopleurid echinoids.
AB  - The phylogenetic relationships of 24 nominal species of temnopleurid echinoid
      were established using molecular and morphological data sets. The analysis
      combined sequence data from mitochondrial 16S rRNA and cytochrome c oxidase
      subunit I genes and the nuclear 18S-like small subunit rRNA gene with
      morphological data concerning coronal, lantern, spine, and pedicellarial traits.
      All four data sets contain similar phylogenetic information, although each
      provides support at a different taxonomic level. Two data congruence tests
      (Templeton's test and the incongruence length difference test) suggested no
      significant heterogeneity between the data sets, and all data were combined in a
      total evidence analysis. The resulting well-resolved phylogeny suggests that
      Microcyphus, Amblypneustes, and Holopneustes are not monophyletic genera, and
      that Temnopleurus (Temnopleurus) and Temnopleurus (Toreumatica) are not closely
      related and should not be regarded as subgenera. In contrast to previous
      morphological analyses, Mespilia is found to be more closely related to
      Temnotrema and Toreumatica than it is to Microcyphus. The phylogeny was used to
      test a series of hypotheses about the evolution of developmental patterns. All
      species of Amblypneustes, Holopneustes, and Microcyphus are lecithotrophic, and
      many of these taxa are restricted to southern Australia. Planktotrophy is the
      ancestral condition for the temnopleurids, and the 11 instances of lecithotrophic
      nonplanktotrophy in this clade can be accounted for by a single developmental
      transition that occurred an estimated 4.4-7.4 million years ago, apparently
      before the migration of Microcyphus to southern Australia. The switch to a
      nonplanktotrophic mode of development is unidirectional with no evidence of
      reversals.

PMID- 12801476
TI  - Phylogenetic studies of Ophioglossaceae: evidence from rbcL and trnL-F plastid
      DNA sequences and morphology.
AB  - Ophioglossaceae are a putatively ancient lineage of ferns in which the aerial
      portion of the plant is composed of a single leaf. The simplicity of foliar
      morphology has limited the number of characters available for constructing
      classifications and contributed to taxonomic difficulties at nearly every level
      of classification within the family. Analysis of plastid DNA rbcL sequences from
      36 species representing the diversity of Ophioglossaceae supported the monophyly
      of the family. Intrafamilial relationships were examined using rbcL and trnL-F
      plastid DNA sequences and morphological data. Individual and combined analyses of
      the three data sets revealed two main clades within the family, here termed
      ophioglossoid and botrychioid. In the botrychioid clade, Helminthostachys was
      sister to a broadly defined Botrychium, within which Botrychium in the narrow
      sense of some authors and Sceptridium were sister. Botrypus was paraphyletic,
      with Botrypus virginianus sister to Botrychium plus Sceptridium, and with
      Botrypus strictus sister to all other botrychioid species except
      Helminthostachys. In the ophioglossoid clade, Ophioglossum in the narrow sense
      was sister to Cheiroglossa plus Ophioderma, but relationships within Ophioglossum
      were not well supported.

PMID- 12801477
TI  - Evolving lineages of Symbiodinium-like dinoflagellates based on ITS1 rDNA.
AB  - Symbiodinium-like dinoflagellates have been shown to be a diverse group of
      endosymbionts that associate mutualistically with many kinds of coral reef
      dwellers, including cnidarians, molluscs, and protists. A high number of
      genetically ITS types of symbionts have been reported to date. However, whether
      these recently identified Symbiodinium ITS types indeed represent independent
      evolutionary lineages is still unsettled. Here I tested the null hypothesis that
      certain group of symbionts sampled from different geographical locations are
      derived from a single evolutionary lineage using a nested clade analysis (NCA). I
      analyzed a total of 174 ITS1 sequences from GenBank and pooled them into 74 ITS1
      distinct haplotypes. Using these haplotypes, the statistical parsimony criterion
      produced 23 independent network trees, each one corresponding to a genetically
      independent evolving lineage. Some of these lineages revealed certain degree of
      specificity with some host groups at least at the phylum level. Within the
      previously described 28S-rDNA phylotype A, five ITS1 lineages were resolved.
      Phylotypes B and C resolved each in two ITS1 lineages. The highest ITS1 symbiont
      diversity was observed within the phylotype F, in which 11 lineages were
      resolved. Moreover, most of these lineages were associated uniquely with protist
      hosts from the group of foraminiferans. Here it is suggested that this high
      genetic diversity of endosymbionts associated with foraminiferans is linked with
      the evolution of soritacean foraminifera, which seems to have been driven by
      endosymbiosis. Lastly, the absence of genetic recombination presented in this
      study, suggest a lack of hybridisation at least among the major 28S-rDNA
      phylotypes within Symbiodinium-like dinoflagellates. This supports highly the
      idea that these phylotypes are indeed independent evolutionary units, which
      should be considered at least as different species. Whether they belong to the
      same genus or to different higher taxa still needs to be revised.

PMID- 12801478
TI  - Magnetic resonance-detected subchondral bone marrow and cartilage defect
      characteristics associated with pain and X-ray-defined knee osteoarthritis.
AB  - OBJECTIVE: To assess whether the presence of subchondral bone marrow
      abnormalities (bone marrow edema (BME)) and cartilage defects, determined by
      magnetic resonance imaging (MRI), would explain the difference between painful
      osteoarthritis of the knee (OAK) compared with painless OAK or pain without OAK.
      METHOD: Four groups of women (30 per group), aged 35-55 years, were recruited
      from the southeast Michigan Osteoarthritis cohort (group 1: painful OAK; group 2:
      painless OAK; group 3: knee pain without OAK; and group 4: no OAK or knee pain).
      OAK was defined by a Kellgren-Lawrence score of 2 or greater, while pain was
      based on self-report. BME and cartilage defects were identified from MRI.
      RESULTS: BME lesions were identified in 56% of all knees. BME lesions were four
      times (95% CI=1.7, 8.7) more likely to occur in the painless OAK group as
      compared with the group with pain, but no OAK. BME lesions >1cm were more
      frequent (OR=5.0; 95% CI=1.4, 10.5) in the painful OAK group than all other
      groups. While the frequency of BME lesions was similar in the painless OAK and
      painful OAK groups, there were more lesions, >1cm, in the painful OAK group.
      About 75% of all knees had evidence of some cartilage defect, of which 35% were
      full-thickness defects. Full-thickness cartilage defects occurred frequently in
      painful OAK. One-third of knees with full-thickness defects and 47% of knees with
      cartilage defects involving bone had BME >1cm. Women with radiographic OA, full
      thickness articular cartilage defects, and adjacent subchondral cortical bone
      defects were significantly more likely to have painful OAK than other groups
      (OR=3.2; 95% CI=1.3, 7.6). CONCLUSION: The finding on MRI of subchondral BME
      cannot satisfactorily explain the presence or absence of knee pain. However,
      women with BME and full-thickness articular cartilage defects accompanied by
      adjacent subchondral cortical bone defects were significantly more likely to have
      painful OAK than painless OAK.

PMID- 12801479
TI  - Association of erosive hand osteoarthritis with a single nucleotide polymorphism
      on the gene encoding interleukin-1 beta.
AB  - OBJECTIVE: Certain forms of primary osteoarthritis (OA), particularly those
      affecting hand joints, have a genetic component. Recent studies have shown
      suggestive evidence that hand and knee OA are linked with the interleukin-1 (IL
      1) region on human chromosome 2q. This study was undertaken to assess the
      association of primary OA of the hand (hand OA) with IL-1 region markers.
      METHODS: Sixty-eight US Caucasoid cases and 51 US Caucasoid controls aged 60
      years or older were recruited from the Mid-Atlantic region of the United States.
      Hand OA was classified by American College of Rheumatology (ACR) Clinical
      Criteria, and cases were subjected to radiographic examination for subgrouping.
      Genotyping was done for seven previously described single nucleotide
      polymorphisms (SNPs) of genes for IL-1alpha (encoded by IL1A), IL-1beta (IL1B),
      and the IL-1 receptor antagonist (IL1RN), as well as an IL1RN variable number of
      tandem repeat (VNTR) marker. Six microsatellite markers on other chromosomes
      (null loci) were also typed. RESULTS: The IL1B 5810 G>A SNP genotypes marker were
      not in Hardy-Weinberg equilibrium (p<0.05 in both non-erosive and erosive hand OA
      subgroups). Statistically significant association with the IL1B 5810 AA genotype
      was found in the erosive hand OA subgroup (relative risk 3.8, p=0.007). This IL1B
      5810 AA genotype association was also significant between erosive and non-erosive
      hand OA subjects (relative risk 4.01, p=0.008). As expected, significant linkage
      disequilibrium was present between IL1B 5810 SNP and IL1A (-)889 SNP, other IL1B
      SNPs, and the nearest IL1RN SNP examined. The IL1B 5810A allele occurs most
      frequently on haplotypes with the SNP alleles IL1B 1423C, IL1B 1903T, IL1B 5887C,
      and IL1A (-)889C. Genotypes at null loci failed to show evidence suggesting
      population stratification that might account for spurious association.
      CONCLUSION: Statistical evidence shows association between erosive hand OA and a
      genomic region containing the IL1B 5810 SNP in a US Caucasoid population. This
      supports a potential role for IL-1 in the pathogenesis of a severe phenotype of
      hand OA.

PMID- 12801480
TI  - A static, closed and scaffold-free bioreactor system that permits chondrogenesis
      in vitro.
AB  - OBJECTIVE: To characterise in vitro engineered cartilaginous constructs made
      employing a novel static, scaffold-free and closed chamber system. DESIGN:
      Chondrocytes derived from slaughter age pigs (3-6 months) were seeded at high
      density (20 x 10(6)) into cylindrical chambers (1.0 x 0.5cm) and were maintained
      between an upper and a lower membrane (100 kDa) for 21 days and subsequently
      cultured in open culture for 7 additional days. RESULTS: Viable constructs
      produced were approximately 10 mmx2mm in size and were stable enough to be
      handled by surgical pincers. Histology and electron microscopy evaluations
      revealed a neo-cartilage structure of high cell density with a comprehensive
      extracellular matrix. Predominately collagen type II and negligible amounts of
      collagen types I and X were detected using RT-PCR and SDS-PAGE analyses.
      CONCLUSIONS: In this study, we provide evidence of a scaffold-free system that
      can produce immature hyaline-like cartilaginous constructs suitable for in vivo
      implantation, or that may be useful for in vitro studies of events related to the
      process of chondrogenesis.

PMID- 12801481
TI  - Quantitative assessment of articular cartilage and subchondral bone histology in
      the meniscectomized guinea pig model of osteoarthritis.
AB  - OBJECTIVE: A new image analysis system was employed to quantify the main
      histological parameters reflecting osteoarthritic features, at the cartilage and
      bone levels, in the meniscectomized guinea pig model of osteoarthritis (OA).
      METHODS: Meniscectomized (MNX) and sham-operated (SH) guinea pigs were studied 1
      and 3 months after partial meniscectomy at the medial side of the left knee (n=10
      to 12 animals/group). The left proximal tibias were included in
      methylmethacrylate. Sections were cut and stained with safranin O or Goldner
      trichrome. Parameters were quantified using special programs of a Biocom image
      analyser. The following parameters were evaluated at the medial side of the
      tibia: cartilage thickness (CT); fibrillation index (FI); proteoglycan content
      ratio based on safranin O staining intensities (PC); chondrocyte density (CD);
      bone volume (BV) and subchondral bone plate thickness (SBPT). The degree of user
      interaction varied from manually tracing objects to almost complete computer
      automation. RESULTS: Meniscectomy resulted in significant variations of these
      reproducible histomorphometric parameters both after 1 month (FI: +522%, P<0.01)
      and 3 months (FI: +162%, P<0.001; PC: -36.7%, P<0.001; CD: -31.8%, P<0.001; SBPT:
      +8.7%, P<0.05) post-operation (results expressed as percentage variation of MNX
      vs SH). The linear correlation analysis including data from SH and/or MNX animals
      at the two grouped time points revealed significant r values, in particular
      between cartilage (CT) and subchondral bone parameters (SBPT) (r=-0.41, P<0.01).
      CONCLUSIONS: Contrary to scoring evaluation, this system allowed to show the time
      dependent impact of the pathology with an early fibrillation of the medial tibial
      cartilage appearing as soon as 1 month post-surgery, and the close relationship
      between bone and cartilage parameters during the progression of OA.

PMID- 12801482
TI  - Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase
      3 synthesized by cultured human osteoarthritis articular chondrocytes.
AB  - OBJECTIVE: The functional integrity of articular cartilage is determined by a
      balance between chondrocyte biosynthesis of extracellular matrix and its
      degradation. In osteoarthritis (OA), the balance is disturbed by an increase in
      matrix degradative enzymes and a decrease in biosynthesis of constitutive
      extracellular matrix molecules, such as collagen type II and aggrecan. In this
      study, we examined the effects of the sulfate salt of glucosamine (GS) on the
      mRNA and protein levels of the proteoglycan aggrecan and on the activity of
      matrix metalloproteinase (MMP)-3 in cultured human OA articular chondrocytes.
      DESIGN: Freshly isolated chondrocytes were obtained from knee cartilage of
      patients with OA. Levels of aggrecan and MMP-3 were determined in culture media
      by employing Western blots after incubation with GS at concentrations ranging
      from 0.2 to 200 microM. Zymography (casein) was performed to confirm that effects
      observed at the protein level were reflected at the level of enzymatic activity.
      Northern hybridizations were used to examine effects of GS on levels of aggrecan
      and MMP-3 mRNA. Glycosaminoglycan (GAG) assays were performed on the cell layers
      to determine levels of cell-associated GAG component of proteoglycans. RESULTS:
      Treatment of OA chondrocytes with GS (1.0-150 microM) resulted in a dose
      dependent increase in aggrecan core protein levels, which reached 120% at 150
      microM GS. These effects appeared to be due to increased expression of the
      corresponding gene as indicated by an increase in aggrecan mRNA levels in
      response to GS. MMP-3 levels decreased (18-65%) as determined by Western blots.
      Reduction of MMP-3 protein was accompanied by a parallel reduction in enzymatic
      activity. GS caused a dose-dependent increase (25-140%) in cell-associated GAG
      content. Chondrocytes obtained from 40% of OA patients failed to respond to GS.
      CONCLUSIONS: The results indicate that GS can stimulate mRNA and protein levels
      of aggrecan core protein and, at the same time, inhibit production and enzymatic
      activity of matrix-degrading MMP-3 in chondrocytes from OA articular cartilage.
      These results provide a cogent molecular mechanism to support clinical
      observations suggesting that GS may have a beneficial effect in the prevention of
      articular cartilage loss in some patients with OA.

PMID- 12801483
TI  - Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in
      healthy male volunteers.
AB  - OBJECTIVE: Chondroitin sulfate (CS) has proven to be a valuable therapeutic tool
      as a symptomatic slow-acting drug for the treatment of osteoarthritis after oral
      administration. The aim of this study was to assess the absorption of CS of
      ichthyic origin after oral administration to 20 healthy male volunteers. DESIGN:
      Ichthyic origin CS (from shark cartilage, 4 g) was orally administered to 20
      healthy human volunteers, and then extracted and purified from plasma over a 48 h
      period. The polysaccharide absorbed by oral route was characterized and
      quantified by agarose-gel electrophoretic technique, and densitometric scanning.
      In addition, the percentage of constituent disaccharides and charge density were
      measured. RESULTS: After oral administration, ichthyic CS plasma levels increased
      (more than 120%) with a peak concentration at 8.7h, with the increase reaching
      significance from 4 to 16 h. A significant decrease in the relative amount of non
      sulfated disaccharide was measured (reaching the minimum relative percentage of
      30.86+/-20.79% at 8h). At the same time, 4-sulfated disaccharide increased to a
      maximum of 51.91+/-25.91% at 6h, and 6-sulfated and disulfated disaccharides
      appeared in blood, reaching maximum concentrations of 15.24+/-16.60% at 8h and
      2.93+/-4.82% at 12h, respectively. Concomitantly, the mean charge density rose
      from 0.40+/-0.14 at predose to a maximum of 0.72+/-0.22 and 0.72+/-0.21 measured
      8 and 12h after ichthyic CS administration. CONCLUSIONS: Ichthyic CS is absorbed
      slowly, with a t(max)=8.7+/-4.5h and the C(max)averaged 4.87+/-2.05 microg/ml.
      The differences in the absorption and bioavailability of the various CS
      formulations is strongly influenced by the structure and characteristics, such as
      molecular mass, charge density, and cluster of disulfated disaccharides, of the
      parental molecules.

PMID- 12801485
TI  - Modification of osteoarthritis by pulsed electromagnetic field--a morphological
      study.
AB  - OBJECTIVE: Hartley guinea pigs spontaneously develop arthritis that bears
      morphological, biochemical, and immunohistochemical similarities to human
      osteoarthritis. It is characterized by the appearance of superficial fibrillation
      by 12 months of age and severe cartilage lesions and eburnation by 18 months of
      age. This study examines the effect of treatment with a pulsed electromagnetic
      field (PEMF) upon the morphological progression of osteoarthritis in this animal
      model. DESIGN: Hartley guinea pigs were exposed to a specific PEMF for 1h/day for
      6 months, beginning at 12 months of age. Control animals were treated
      identically, but without PEMF exposure. Tibial articular cartilage was examined
      with histological/histochemical grading of the severity of arthritis, by
      immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting
      enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13)
      and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and
      IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible
      mechanisms of PEMF activity. RESULTS: PEMF treatment preserves the morphology of
      articular cartilage and retards the development of osteoarthritic lesions. This
      observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and
      BC-13, and suppression of the matrix-degrading enzymes, collagenase and
      stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP
      positive cells are increased in response to treatment. PEMF treatment markedly
      increases the number of cells immunopositive to TGFbeta. CONCLUSIONS: Treatment
      with PEMF appears to be disease-modifying in this model of osteoarthritis. Since
      TGFbeta is believed to upregulate gene expression for aggrecan, downregulate
      matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix
      metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF
      favorably affects cartilage homeostasis.

PMID- 12801484
TI  - Effect of cartilage oligomeric matrix protein on mesenchymal chondrogenesis in
      vitro.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) mutations have been
      identified as responsible for two arthritic disorders, multiple epiphyseal
      dysplasia (MED) and pseudoachondroplasia (PSACH). However, the function of COMP
      in chondrogenic differentiation is largely unknown. Our investigation focuses on
      analyzing the function of normal COMP protein in cartilage biology. METHODS AND
      RESULTS: To explore the function of COMP we make use of an in vitro model system
      for chondrogenesis, consisting of murine C3H10T1/2 mesenchymal cells maintained
      as a high-density micromass culture and stimulated with bone morphogenetic
      protein 2 (BMP-2). Under these culture conditions, C3H10T1/2 cells undergo active
      chondrogenesis in a manner analogous to that of embryonic limb mesenchymal cells,
      and have been shown to serve as a valid model system to investigate the
      mechanisms regulating mesenchymal chondrogenesis. Our results indicate that
      ectopic COMP expression enhances several early aspects of chondrogenesis induced
      by BMP-2 in this system, indicating that COMP functions in part to positively
      regulate chondrogenesis. Additionally, COMP has inhibitory effects on
      proliferation of cells in monolayer. However, at later times in micromass
      culture, ectopic COMP expression in the presence of BMP-2 causes an increase in
      apoptosis, with an accompanying reduction in cell numbers in the micromass
      culture. However, the remaining cells retain their chondrogenic phenotype.
      CONCLUSIONS: These data suggest that COMP and BMP-2 signaling converge to
      regulate the fate of these cells in vitro by affecting both early and late stages
      of chondrogenesis.

PMID- 12801486
TI  - Thyroxine stimulates transglutaminase activity in articular chondrocytes.
AB  - OBJECTIVES: Thyroid hormones induce features of the hypertrophic phenotype in
      mature articular chondrocytes as well as in growth plate chondrocytes.
      Hypertrophic chondrocytes are responsible for extracellular matrix
      mineralization, with formation of bone mineral in growth plate cartilage and
      pathologic calcium crystals in aging articular cartilage. Elevated activity
      levels of the two transglutaminase (Tgase) enzymes (type II Tgase and Factor
      XIIIA (FXIIIA)) have recently been described as additional features of
      hypertrophic growth plate chondrocytes. Because Tgases may participate in
      pathologic mineralization in aging cartilage, we explored the effects of thyroid
      hormones on Tgase activity in articular chondrocytes. METHODS: Adult porcine
      articular chondrocytes were incubated with or without 250-750nM L-thyroxine (T4)
      or 10-100 nM 3,3',5-tri-iodothyronine (T3). Tgase activity was measured with a
      standard radiometric assay. The effects of thyroid hormones on protein and mRNA
      levels of type II Tgase and FXIIIA were determined. As Tgase activity can be
      stimulated by proteases, endoproteinase levels were also measured. The mechanisms
      of these effects were explored. RESULTS: T4 (750 nM) or T3 (100 nM) stimulated
      Tgase activity by twofold in articular chondrocytes at 4h and increased the
      percentage of Tgase activity in the extracellular matrix. Chondrocytes rapidly
      converted T4 to T3, but the time course suggests similar mechanisms for T4 and
      T3. T4-induced Tgase activity was suppressed with cycloheximide and protein
      kinase C inhibitors. The effects of T4 on type II Tgase and FXIIIA levels were
      modest, but T4 strongly induced endoproteinase activity in chondrocytes.
      CONCLUSIONS: We report in this study that thyroid hormones increase Tgase
      activity in articular chondrocytes via a non-genomic mechanism, which may involve
      increased endoproteinase secretion.

PMID- 12801488
TI  - Online consultation.

PMID- 12801489
TI  - Complementary medicine research in Exeter: the first decade.

PMID- 12801490
TI  - The effects of homeopathic Argentum nitricum on test anxiety.
AB  - OBJECTIVES: (1) To replicate a study of the efficacy of Argentum nitricum 12X in
      the reduction of test anxiety as demonstrated previously. (2) To investigate the
      correlation between individuals identified to match the A. nitricum profile and
      the reduction of test anxiety. To compare traditionally prepared homeopathic A.
      nitricum 12X with radionically-prepared A. nitricum 12X and placebo. DESIGN: A
      double blind, placebo-controlled, randomised clinical trial with three arms.
      SETTING: The study was conducted at Southern Cross University, Lismore,
      Australia. SUBJECTS: Sixty-two test anxious university students. INTERVENTIONS:
      Subjects were randomised to one of three groups: traditionally prepared
      homeopathic A. nitricum 12X, radionically-prepared A. nitricum 12X, or placebo.
      After screening, each group received treatment twice a day for 4 days after which
      they were re-tested. OUTCOME MEASURES: Primary: The Revised Test Anxiety Scale.
      Secondary: The Test Anxiety Scale; 36-item A. nitricum questionnaire. RESULTS:
      The results of this study did not replicate the Stanton study. No correlation
      between the reduction of test anxiety and the A. nitricum profile was
      demonstrated. No significant differences between treatments were demonstrated.
      CONCLUSION: This study demonstrated that homeopathic A. nitricum 12X does not
      reduce test anxiety in a general population of university students.

PMID- 12801491
TI  - Continuous PC6 wristband acupressure for relief of nausea and vomiting associated
      with acute myocardial infarction: a partially randomised, placebo-controlled
      trial.
AB  - OBJECTIVES: To assess the effectiveness of continuous PC6 acupressure as an
      adjunct to antiemetic drug therapy in the prevention and control of nausea and
      vomiting in the first 24h after myocardial infarction (MI). DESIGN: Partially
      randomised, partially blinded placebo-controlled, exploratory clinical study.
      SETTING: Coronary Care Unit, Torbay Hospital, Torquay, Devon. PARTICIPANTS: A
      total of 301 consecutive patients (205 males, 96 females) admitted following
      acute MI. INTERVENTION: The first 125 patients recruited received no additional
      intervention. Subsequent patients were randomised to receive either continuous
      PC6 acupressure or placebo acupressure. OUTCOME MEASURES: (1) Incidence of post
      MI nausea and/or vomiting, (2) severity of symptoms, (3) use of antiemetic drugs,
      over 24h. RESULTS: There were no significant differences between the groups for
      the whole 24-h treatment period. However, the PC6 acupressure group experienced
      significantly lower incidence of nausea and/or vomiting during the last 20h
      (18%), compared with the placebo (32%) or control (43%) groups (P<0.05). The
      severity of symptoms and the need for antiemetic drugs were also reduced in the
      acupressure group, but these differences were not statistically significant.
      CONCLUSIONS: Continuous 24-h PC6 acupressure therapy as an adjunct to standard
      antiemetic medication for post-MI nausea and vomiting is feasible and is well
      accepted and tolerated by patients. In view of its benefits, further studies are
      worthwhile using earlier onset of treatment.

PMID- 12801492
TI  - Treating dyspepsia with acupuncture and homeopathy: reflections on a pilot study
      by researchers, practitioners and participants.
AB  - OBJECTIVES: For people with dyspepsia who are receiving orthodox general practice
      care, what is the effect on outcome and on NHS costs of adding treatment by a
      choice of acupuncture or homeopathy? This paper describes and reflects upon a
      pilot study with user involvement. DESIGN: A randomised pilot study. Patients
      chose between acupuncture and homeopathy and were then randomised to this
      preference or to the control group of normal GP care. SETTING AND PARTICIPANTS:
      Sixty people with dyspepsia (>/=2 weeks) presenting in one UK general practice
      were recruited in consultations and by letter to those on repeat prescriptions.
      There were few exclusion criteria. The homeopath and the acupuncturist treated
      the patient individually according to their normal practice for up to 6 months.
      After the trial there was a focus group for participants. OUTCOME MEASURES: SF-36
      health survey, Measure Yourself Medical Outcome Profile (MYMOP), and General Well
      being Index (GWBI). Counts of prescriptions, consultations and referrals from
      practice computer records. RESULTS: No trend or significant difference between
      the groups for clinical outcome or NHS costs. Major costs for the 6 months, mean
      (S.D.) cost per patient, were general practitioner consultations pound 8 (18),
      prescriptions pound 64 (73), acupuncture pound 175 (52), homeopathy pound 105
      (33). Participants gave insights and suggestions which will inform the full trial
      design. CONCLUSIONS: Reflection on the pilot study data and experience by
      participants, treating practitioners and researchers led to modifications in the
      design and a sample size calculation. How to demonstrate individual responses to
      treatment remains a problem.

PMID- 12801493
TI  - The long-term effects of auricular therapy using magnetic pearls on elderly with
      insomnia.
AB  - OBJECTIVE: To examine the long-term effect of auricular therapy using magnetic
      pearls administered for the elderly suffering from insomnia. DESIGN: A follow-up
      study after a randomized controlled trial. SETTINGS: Four hostels for the elderly
      in Hong Kong. INTERVENTIONS: This paper focuses on reporting the long-term effect
      of auricular therapy using magnetic pearls in the experimental group of a
      randomized controlled study. Fifteen volunteer participants were followed up at 1
      , 3-, and 6-month intervals after a 3-week treatment course. OUTCOME MEASURES:
      Objective sleep parameters using actigraphic monitoring were collected at
      different intervals of time after the therapy. RESULTS: Results of RANOVA
      demonstrate that there was a significant difference of nocturnal sleep time
      (F(2.30,29.90)=3.63, P<0.05) and marginally differences of sleep efficiency
      (F(4,52)=2.52, P=0.05) at baseline, immediately after the therapy, and at the
      three time intervals at 1, 3 and 6 months. The results illustrate that the mean
      nocturnal sleep time (F=4.95, P=0.30, R(2)=0.91) and the mean sleep efficiency
      (F=13.50, P=0.19, R(2)=0.96) also remained constant over the 6-month follow up
      period. The results of least square polynomial regression analysis also
      illustrate that the mean NST (F=4.95, P=0.30, R(2)=0.91) and the mean sleep
      efficiency (F=13.50, P=0.19, R(2)=0.96) remained constant over the 6-month follow
      up period. CONCLUSION: The results of this follow up study indicate that
      auricular therapy using magnetic pearls could have a long-term effect, at least
      within the observed period of time, on improving the quality as well as the
      quantity of sleep among the elderly.

PMID- 12801494
TI  - Incidence of adverse effects during acupuncture therapy-a multicentre survey.
AB  - INTRODUCTION: Acupuncture is frequently used to treat chronic pain syndromes or
      other chronic diseases. Several hundred reports have been published of life
      threatening adverse events after acupuncture. The aim of our study was to assess
      the adverse effects of acupuncture during a normal treatment routine. METHODS:
      Thirteen general practitioners and outpatient clinics and 16 other practitioners
      were included in a questionnaire survey in Germany. Patient gender and age,
      indications for and method of treatment, and adverse effects were documented by
      the therapists. RESULTS: Four hundred and nine patients receiving 3535
      acupuncture treatment were included. Adverse effects were observed in 402
      treatments (11.4%) in 153 different patients. The main side effects were slight
      haemorrhage (2.9%), haematoma (2.2%), dizziness (1%) and other systemic symptoms
      (2.7%). Other side effects mentioned (all below 1%) were fainting, nausea,
      prolonged DeQi effect (paraesthesia) and increase of pain. In one case, aphasia
      was reported lasting 1h after acupuncture. CONCLUSION: Acupuncture has adverse
      effects, like any therapeutic approach. If it is used according to established
      safety rules and carefully at appropriate anatomic regions, it is a safe
      treatment method.

PMID- 12801495
TI  - Reflexologists' responses to a patient with abdominal pain-a survey on Internet
      advice.
AB  - OBJECTIVE: To generate preliminary data on how individual reflexologists deal
      with patients seeking medical advice on the Internet. DESIGN: E-mail survey
      involving reflexologists who were partly blinded for their advice on the
      Internet. SETTING: Cyberspace. PARTICIPANTS: Two hundred and seventy-seven
      members of the Association of Reflexologists. Of 842 e-mails sent out we received
      323 responses (38% response rate) of which 46 participants later withdrew their
      responses (14% withdrawal rate). INTERVENTION: Participants were asked to advise
      a fictitious patient via e-mail who presented various health problems. MAIN
      OUTCOME MEASURE: Rating of responses according to safety and claims made by
      reflexologist sample. RESULTS: Eighty-five percent of all respondents advised the
      fictitious patient to present the health problems to a medical professional.
      Fifty-eight percent expressed urgency to see a primary care physician or other
      health care professional and 95% pointed out that a diagnosis cannot and should
      not be made by a reflexologist. Twenty-nine percent of responders suggested a
      differential diagnosis or underlying causes for the patient's condition.
      CONCLUSIONS: In this survey reflexologists from the UK Association of
      Reflexologists have responded in an encouraging manner to a fictitious patient's
      request for health advice via electronic mail as only 5% (or possibly 15%) of
      reflexologists from this survey need to be more cautious about the advice they
      give their patients. We hope that our study will further encourage therapists to
      be more cautious giving Internet health advice in the future.

PMID- 12801496
TI  - Attitudes of Hong Kong Chinese to traditional Chinese medicine and Western
      medicine: survey and cluster analysis.
AB  - OBJECTIVES: To determine whether within a cohort of Hong Kong out-patients
      definable subtypes exist based on their attitudes to traditional Chinese medicine
      and Western medicine. DESIGN: Data were collected using a structured
      questionnaire. SETTING: The sample of 503 subjects was recruited at two local
      outpatient clinics in Hong Kong. MAIN OUTCOME MEASURES: The study employs
      demographic variables, illness status, the Chinese-Western Medical Belief Scale,
      trust of physicians and subjects' preferences on consultation fees, attitude of
      health care professional, efficacy of service and waiting time during
      consultation. RESULTS: A cluster analysis yielded three clusters based on their
      attitudes towards traditional Chinese and Western medicine. One cluster, 24% of
      the sample, is noted for being older, poorer, more likely to be female and to
      have chronic conditions; they are sceptical of western physicians. The second
      cluster (63% of the sample) is younger and have considerably more belief in
      Western than traditional Chinese medicine. The third group (14%) is intermediate
      in age and is noted for a marked faith in both forms of medicine. CONCLUSIONS: A
      clear profile of these attitudes of Hong Kong Chinese may benefit health care
      professionals in making appropriate patient-doctor relationships and planning
      patient care.

PMID- 12801497
TI  - Attitudes of GPs towards the provision of acupuncture on the NHS.
AB  - OBJECTIVE: To investigate the attitudes of General Practitioners (GPs) to
      acupuncture, whether they think it should be available on the NHS and, if so, how
      it should be provided. DESIGN: Attitudinal postal survey. SETTING: All 65
      practising GPs in the 12 GP practices of the Melton Rutland & Harborough Primary
      Care Group, UK. RESULTS: A response rate of 83% was achieved. The main findings
      show that 59% of GPs agreed that acupuncture should be available on the NHS, 83%
      agreed that it can be clinically useful and 72% that it can be cost effective.
      Among GPs who acknowledged the potential for an increased role for acupuncture on
      the NHS there was support for the provision of treatment from either medical or
      non-medical practitioners, delivered at either NHS or non-NHS premises, and with
      the NHS providing some, or all, of the required funding. CONCLUSION: The findings
      suggest that a majority of GPs are in favour of acupuncture being more widely
      available on the NHS.

PMID- 12801498
TI  - Can we evaluate electrodermal testing?
AB  - Electrodermal testing (ED testing) is an acupuncture-based approach and was
      developed to refine homeopathic prescriptions. It is currently being used to
      advise patients about their "allergies". The evidence for its use in "allergy
      testing" is limited and often misrepresented. This article addresses the research
      and clinical issues involved in investigating the reliability and validity of
      various ED testing machines.

PMID- 12801499
TI  - Use of animal products in traditional Chinese medicine: environmental impact and
      health hazards.
AB  - Traditional Chinese medicine (TCM) has been increasingly practised in many
      countries of the world. Some recent textbooks of TCM still recommend formulas
      containing various animal tissues such as tiger bones, antelope, buffalo or rhino
      horns, deer antlers, testicles and os penis of the dog, bear or snake bile.
      Usually, animal tissues are combined with medical herbs. In most of the cases,
      the medical use of the preparations is justified in terms of the rules of TCM. So
      far, little research has been done to prove the claimed clinical efficacy of TCM
      animal products. This paper discusses some related ecological, ethico-legal and
      health concerns such as hunting, breeding and trade with endangered species,
      risks of transmission of zoonoses, quality of the products, and alternatives to
      preparations from endangered species.

PMID- 12801500
TI  - The terms 'acupuncture' and 'placebo' should be adequately defined in clinical
      trials.

PMID- 12801504
TI  - Meeting the impact of the traditional herbal medicinal products directive.
      Conference organised by the British Institute of Regulatory Affairs, London, UK,
      January 2003.

PMID- 12801506
TI  - Ubiquitin-independent proteolytic functions of the proteasome.
AB  - The discovery of the 20S proteasome (multicatalytic proteinase complex) was
      followed by the recognition that this multisubunit macromolecule is the
      proteolytic core of the 26S proteasome. Most of the research on extralysosomal
      proteolysis has concentrated on the role of the 26S proteasome in the ubiquitin
      dependent proteolytic pathway. However, little attention has been directed toward
      the possible involvement of the proteasome in ubiquitin-independent proteolysis.
      In the past few years, many publications have provided evidence that both the 20S
      proteasome and the 26S proteasome can degrade some proteins in an ubiquitin
      independent manner. Furthermore, it is becoming clear that demonstration of
      ubiquitin-protein conjugates after exposure of cells to proteasome inhibitors
      does not eliminate the possibility that the same protein can also be degraded by
      the proteasome without ubiquitination. The possible mechanisms of degradation of
      an unmodified protein by the 20S proteasome are discussed. These include
      targeting, protein unfolding, and opening of the gated channel to the catalytic
      sites. It is reasonable to assume that in the future the number of proteins
      recognized as substates of the ubiquitin-independent pathway will continue to
      increase, and that the metabolic significance of this pathway will be clarified.

PMID- 12801507
TI  - Mechanism of simvastatin on induction of heat shock protein in osteoblasts.
AB  - It has recently been reported that 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) stimulate bone formation. However, the mechanism
      of stimulation of bone metabolism by statins is not precisely clarified. In this
      study, we investigated whether simvastatin induces heat shock protein (HSP) 27,
      HSP70, and HSP90 in osteoblast-like MC3T3-E1 cells. Simvastatin increased the
      levels of HSP27 while having little effect on the levels of HSP70 or HSP90. The
      effect of simvastatin on HSP27 accumulation was dose dependent. Cycloheximide
      reduced the accumulation. Simvastatin induced an increase in the levels of mRNA
      for HSP27. Actinomycin D suppressed the mRNA levels. Simvastatin induced the
      phosphorylation of p38 mitogen-activated protein (MAP) kinase among the MAP
      kinase superfamily. SB203580 and PD169316, inhibitors of p38 MAP kinase,
      suppressed the HSP27 accumulation by simvastatin while SB202474, a negative
      control of p38 MAP kinase inhibitor, had no effect. SB203580 reduced the
      simvastatin-increased mRNA levels for HSP27. Lovastatin, another statin, also
      induced the HSP27 accumulation and SB203580 suppressed the HSP27 accumulation.
      These results strongly suggest that statins such as simvastatin do not stimulate
      the induction of HSP70 and HSP90, but do stimulate the induction of HSP27 in
      osteoblasts and that p38 MAP kinase plays a role in this induction.

PMID- 12801508
TI  - Purification and characterization of the aromatic desulfinase, 2-(2'
      hydroxyphenyl)benzenesulfinate desulfinase.
AB  - 2-(2(')-Hydroxyphenyl)benzenesulfinate desulfinase (HPBS desulfinase) catalyzes
      the cleavage of the carbon-sulfur bond of 2-(2(')-hydroxyphenyl)benzenesulfinate
      (HPBS) to form hydroxybiphenyl and sulfite. This is the final step in the
      desulfurization of dibenzothiophene, the organosulfur compound used to study
      biodesulfurization of petroleum middle distillate. HPBS desulfinase was purified
      1600-fold from Rhodococcus IGTS8. The purification was monitored using a
      spectrofluorimetric assay and SDS-PAGE. The pI of HPBS desulfinase is 5.6, the
      temperature optimum is 35 degrees C, and the pH optimum is 7.0. HPBS desulfinase
      has a K(m) of 0.90+/-0.15 microM and a k(cat) of 1.3+/-0.07 min(-1). Several
      analogs were tested for their ability to act as substrates or inhibitors of HPBS
      desulfinase. No alternative substrates and very few inhibitors were identified.
      HPBS desulfinase activity decreases in the presence of Cu(2+) and Zn(2+), while
      no metals significantly enhance enzyme activity. HPBS desulfinase is susceptible
      to tyrosine, tryptophan, and cysteine specific modification agents.

PMID- 12801509
TI  - Amino acid sequence, biochemical characterization, and comparative modeling of a
      nonspecific lipid transfer protein from Amaranthus hypochondriacus.
AB  - Plant nonspecific lipid transfer proteins (nsLTPs) are characterized by their
      ability to bind a broad range of hydrophobic ligands in vitro. Their biological
      function has not yet been elucidated, but they could play a major role in plant
      defense to physical and biological stress. An nsLTP was isolated from Amaranthus
      hypochondriacus seeds and purified by gel filtration and reversed-phase high
      performance liquid chromatography techniques. The molecular mass of the protein
      as determined by mass spectrometry is 9747.29 Da. Data from amino acid sequence,
      circular dichroism and binding/displacement of a fluorescent lipid revealed that
      it belongs to the nsLTP1 family. The protein shows the alpha-helical secondary
      structure typical for plant nsLTPs 1 and shares 40 to 57% sequence identity with
      nsLTPs 1 from other plant species and 100% identity with an nsLTP1 from
      Amaranthus caudatus. A model structure of the protein in complex with stearate
      based on known structures of maize and rice nsLTPs 1 suggests a protein fold
      complexed with lipids closely related to that of maize nsLTP1.

PMID- 12801510
TI  - Inhibition of taurolithocholate 3-sulfate-induced apoptosis by cyclic AMP in rat
      hepatocytes involves protein kinase A-dependent and -independent mechanisms.
AB  - The mechanisms underlying the inhibition of bile acid-induced apoptosis by cyclic
      AMP (cAMP) were studied in 24-h-cultured rat hepatocytes. Taurolithocholate 3
      sulfate (TLCS, 100 micromol/l) led to a sustained activation of mitogen activated
      protein (MAP) kinases (JNK, p38(MAPK), and ERKs), dephosphorylation of protein
      kinase B (PKB), activation of caspases 3 and 8, and hepatocyte apoptosis. cAMP
      prevented TLCS-induced apoptosis, shifted the persistent TLCS-induced MAP kinase
      response to a transient pattern, and prevented PKB dephosphorylation. TLCS
      induced CD95 and TRAIL receptor-2 trafficking to the plasma membrane were
      significantly inhibited. Blockade of protein kinase A (PKA) abolished the
      inhibitory effect of cAMP on TLCS-induced CD95 membrane targeting, but not TRAIL
      receptor-2 membrane targeting, PKB and MAP kinase responses. H89, an inhibitor of
      PKA, had no effect on cAMP-induced inhibition of TLCS-triggered poly(ADP) ribose
      polymerase (PARP) cleavage and caspase activation, but abolished the cAMP-induced
      inhibition of TLCS-triggered TUNEL- and Annexin V staining. It is concluded that
      cAMP inhibits bile acid-induced apoptosis via PKA-dependent and -independent
      mechanisms.

PMID- 12801511
TI  - Phospholipid vesicle fusion induced by saposin C.
AB  - Saposin C is a small Trp-free, multifunctional glycoprotein that enhances the
      hydrolytic activity of acid beta-glucosidase in lysosomes. Saposin C's functions
      have been shown to include neuritogenic/neuroprotection effects and membrane
      fusion induction. Here, the mechanism and kinetics of saposin C's fusogenic
      activity were evaluated by fluorescence spectroscopic methods including
      dequenching, fluorescence resonance energy transfer, and stopped-flow analyses.
      Trp or dansyl groups were introduced as fluorescence reporters into selected
      sites of saposin C to serve as topological probes for protein-protein and protein
      membrane interactions. Saposin C induction of liposomal vesicle enlargement was
      dependent upon anionic phospholipids and acidic pH. The initial fusion burst was
      completed in the timeframe of a few seconds to minutes and was dependent upon the
      unsaturated anionic phospholipid content. Two events were associated with saposin
      C-membrane interaction: membrane insertion of the saposin C terminal helices and
      reorientation of its central helical region. The latter conformational change
      likely exposed a binding site for saposins anchored on vesicles. Addition of
      selected saposin C peptides prior to intact saposin C in reaction mixtures
      abolished the liposomal fusion. These results indicated that saposin-membrane and
      saposin-saposin interactions are needed for the fusion process.

PMID- 12801512
TI  - Chimeric exchanges within the bradykinin B2 receptor intracellular face with the
      prostaglandin EP2 receptor as the donor: importance of the second intracellular
      loop for cAMP synthesis.
AB  - The prostaglandin E2 (PGE(2)) EP2 receptor (EP2R) type is G protein coupled
      (GPCR) and links to Galphas. Through this receptor PGE(2) activates cAMP
      production. The bradykinin (BK) B2 receptor (BKB2R) is also a GPCR but links to
      Galphaq and Galphai and does not activate cAMP production in response to
      bradykinin. In an attempt to convert the BKB2R into a Galphas-linked adenylate
      cyclase-activating receptor we proceeded to make global and discrete motif
      replacements of the intracellular (IC) face of the BKB2R with the corresponding
      regions of the human EP2R. With this approach we produced hybrid receptors which,
      when stably transfected into wild type (WT) Rat-1 cells, bound BK but produced
      cAMP. Replacement of the second loop (IC2), third loop (IC3), the entire C
      terminus, and the distal C terminus resulted in receptors which bound BK.
      However, only the IC2 and IC3 exchanges resulted in cAMP-producing receptors. Of
      these two regions, the IC2 exchange was by far the better cAMP-generating
      receptor, producing cAMP at approximately 6.6-fold above WT BKB2R or
      approximately one fourth the amount produced by WT EP2R-transfected Rat-1 cells.
      Both human and rat EP2R and human beta2-adrenergic receptor exchanges of the IC2
      produced equal quantities of cAMP. Focusing on the rBKB2R/hEP2R IC2 chimeras, the
      region consisting of residues 136-147 (BKB2R residue numbering) proved to contain
      a cAMP-generating motif. Within this region, the proximal six amino acids from
      the EP2R (HPYFYQ) at position 136-141 proved crucial for cAMP production (10-fold
      over WT BKB2R). The distal part of this region, the six residues at 142-147,
      played no role in cAMP production. On the other hand, the ALV motif of the BKB2R
      IC2, residues 133-135, proved important with respect to phosphatydilinositol (PI)
      turnover. Replacing the entire IC2 of BKB2R resulted in poor PI turnover, while
      including the AVL of BKB2R retained approximately half of the WT PI turnover.
      With respect to receptor uptake, all the IC2 mutants endocytosed as WT BKB2R (60%
      in 1h). However, the exchange of the distal and the whole C termini resulted in a
      marked drop in endocytosis (30% in 1h). These results demonstrate that the
      construction of a cAMP-producing BKB2/EP2 receptor hybrid is possible, with the
      IC2 region distal to DRYLALV proving important to Galphas linkage and the LALV
      motif within the IC2 of BKB2R and the region proximal to it proving important for
      Galphaq and Galphai linkage. Additionally, our results confirm the importance of
      the distal C terminus in determining receptor uptake.

PMID- 12801513
TI  - Possible involvement of mitogen-activated protein kinase in the angiotensin II
      induced fibronectin synthesis in renal interstitial fibroblasts.
AB  - Angiotensin II (AT II) is thought to be associated with the development of renal
      interstitial fibrosis. However, the molecular mechanisms of the interstitial
      fibrosis have not been extensively studied. We have examined the role of mitogen
      activated protein kinases (MAPKs) on fibronectin (FN) accumulation in cultured
      normal rat kidney interstitial fibroblasts (NRK 49F cell line). AT II caused dose
      dependent increases in FN accumulation and FN mRNA in these cells. AT II also
      activated the extracellular signal-regulated kinase (ERK) and p38 MAPK in the
      presence of AT II. These increases in FN accumulation and activation of MAPKs
      were inhibited with AT I receptor antagonist (ARB; CV-11974) in renal
      interstitial fibroblasts. The inhibitors against ERK (PD98059) and p38 MAPK
      (SB203580) significantly inhibited AT II-induced increases in FN mRNA. These
      findings suggest that the MAPKs play an important role in AT II-mediated renal
      interstitial fibrosis and that ARB may be useful for preventing renal
      interstitial fibrosis.

PMID- 12801514
TI  - Transport and binding of insulin-like growth factor I through articular
      cartilage.
AB  - This study focused on the role of insulin-like growth factor (IGF) binding
      proteins (IGFBPs) in cartilage on the transport and binding of IGF-I within the
      tissue. We have developed experimental and theoretical modeling techniques to
      quantify and contrast the roles of diffusion, binding, fluid convection, and
      electrical migration on the transport of IGF-I within cartilage tissue. Bovine
      articular cartilage disks were equilibrated in buffer containing 125I-IGF-I and
      graded levels of unlabeled IGF-I. Equilibrium binding, as measured by the uptake
      ratio of 125I-IGF-I in the tissue (free plus bound) to the concentration of
      labeled species in the buffer, was found to be consistent with a first-order
      reversible binding model involving one dominant family of binding sites within
      the matrix. Western ligand blots revealed a major IGF binding doublet around 23
      kDa, which has been previously shown to coincide with IGFBP-6. Diffusive
      transport of 125I-IGF-I through cartilage was measured and found to be consistent
      with a diffusion-limited reaction theoretical model incorporating first-order
      reversible binding. Addition of excess amounts of unlabeled IGF-I during steady
      state transport of 125I-IGF-I resulted in release of bound 125I-IGF-I from the
      tissue, as predicted by the diffusion-reaction model. In contrast, addition of
      the low-affinity Des(1-3)IGF-I analog did not result in release of bound 125I-IGF
      I. Application of electric current was used to augment transport of IGF-I through
      cartilage via electroosmosis and electrophoresis. Taken together, our results
      suggest that a single dominant substrate family, the high-affinity IGFBPs, is
      responsible for much of the observed binding of IGF-I within cartilage. The data
      suggest that intratissue fluid flow, such as that induced by mechanical loading
      of cartilage in vivo may be expected to enhance IGF transport by an order of
      magnitude and that this increment may help to counterbalance the restrictions
      encountered by the immobilization of IGFs by the binding proteins.

PMID- 12801515
TI  - Proteolytic cleavage of the puromycin-sensitive aminopeptidase generates a
      substrate binding domain.
AB  - The puromycin-sensitive aminopeptidase was found to be resistant to proteolysis
      by trypsin, chymotrypsin, and protease V8 but was cleaved into an N-terminal 60
      kDa fragment and a C-terminal 33-kDa fragment by proteinase K. The two proteinase
      K fragments remain associated and retained enzymatic activity. Attempts to
      express the 60-kDa N-terminal fragment in Escherichia coli produced inclusion
      bodies. A hexa-histidine fusion protein of the 60-kDa N-terminal fragment was
      solubilized from inclusion bodies with urea and refolded by removal of the urea
      through dialysis. The refolded protein was devoid of aminopeptidase activity as
      assayed with arginine-beta-naphthylamide. However, the refolded protein bound the
      substrate dynorphin A(1-9) with a stoichiometry of 0.5 mol/mol and a K(0.5) value
      of 50 microM. Dynorphin A(1-9) binding was competitively inhibited by the
      substrate dynorphin B(1-9), but not by des-Tyr(1)-leucine-enkephalin, a poor
      substrate for the enzyme.

PMID- 12801516
TI  - Unique metal dependency of cytosolic alpha-mannosidase from Thermotoga maritima,
      a hyperthermophilic bacterium.
AB  - A putative cytosolic alpha-mannosidase gene from a hyperthermophilic marine
      bacterium Thermotoga maritima was cloned and expressed in Escherichia coli. The
      purified recombinant enzyme appeared to be a homodimer of a 110-kDa subunit. The
      enzyme showed metal-dependent ability to hydrolyze p-nitrophenyl-alpha-D
      mannopyranoside. In the absence of a metal, the enzyme was inactive. Cobalt and
      cadmium supported high activity (60 U/mg at 70 degrees C), while the activity
      with zinc and chromium was poor. Cobalt (0.8 mol) bound to 1 mol monomer with a
      K(d) of 70 microM. The optimum pH and temperature were 6.0 and 80 degrees C,
      respectively. The activity was inhibited by swainsonine, but not by 1
      deoxymannojirimycin, which is in agreement with the features of cytosolic alpha
      mannosidase.

PMID- 12801517
TI  - A protein isolated from Escherichia coli, identified as GroEL, reacts with anti
      beta spectrin antibodies.
AB  - We found that a protein of molecular weight close to 65kDa, present in
      Escherichia coli cells, reacts with anti-beta spectrin antibodies. A method of
      purification of this protein was designed. The method consists of the following:
      nonionic detergent extraction, gel filtration chromatography, ion-exchange
      chromatography using DEAE-Servacell, and two FPLC ion-exchange chromatography
      runs: the first without urea, the second in its presence. This method allowed us
      to obtain a highly purified protein. The results of mass spectrometry analysis
      suggest that the investigated protein is GroEL (Hsp60 Class). Using computer
      programs, by sequence analysis of both proteins we tried to explain why GroEL
      isolated from E. coli reacts with anti-beta spectrin antibodies. Both proteins
      may share a single epitope for the antibodies on their surfaces. Additionally,
      such an assumption is supported by the results of experiments in which antibodies
      interacting with GroEL were obtained from anti-beta spectrin serum and were shown
      to react with both GroEL and beta spectrins.

PMID- 12801519
TI  - Biological and dietary antioxidants protect against DNA nitration induced by
      reaction of hypochlorous acid with nitrite.
AB  - Nitryl chloride, formed by reaction of hypochlorous acid with nitrite, might
      contribute to nitrative damage of biomolecules in addition to peroxynitrite.
      Damage of DNA by these reactive nitrogen oxide species is implicated in
      carcinogenesis associated with chronic infections and inflammation. Nitrated DNA
      adducts, such as 8-nitroguanine and 8-nitroxanthine, are not stable in DNA since
      they undergo spontaneous depurination, leading to apurinic site formation. In
      this report, we investigate the protective effect of biological and dietary
      antioxidants in inhibiting DNA nitration induced by nitryl chloride. The effect
      of inhibition was evaluated by decrease of 8-nitroxanthine and 8-nitroguanine
      formation. Among the 21 compounds examined, dihydrolipoic acid is the most
      effective in preventing DNA nitration, followed by N-acetyl-L-cysteine and folic
      acid. For sulfur-containing compounds, the more highly reduced compounds are
      stronger inhibitors of DNA nitration. The major product of N-acetyl-L-cysteine
      reaction with nitryl chloride is characterized as the (R)-2-acetylamino-3
      sulfopropionic acid, a physiologically irreversible product, suggesting that
      nitryl chloride is a strong oxidizing agent.

PMID- 12801518
TI  - Novel anticoagulant polyethylenimine: inhibition of thrombin-catalyzed fibrin
      formation.
AB  - Hypercoagulability is often associated with a variety of disease states, leading
      to cardiovascular complications. Polyethylenimine (PEI) prolonged prothrombin
      time, demonstrating its anticoagulant potential. In vitro, PEI at low
      concentration (nM) significantly blocked thrombin-catalyzed fibrin formation,
      accounting for its mode of anticoagulation. The uncompetitive inhibition by PEI
      of fibrin formation was independent of the concentration of fibrinogen (FBG),
      thrombin, or NaCl. PEI showed no effect on thrombin amidolytic activity,
      suggesting that the blockade of thrombin interaction with FBG could account for
      the inhibition on fibrin formation. PEI drastically depressed rabbit brain
      thromboplastin procoagulation monitored by a single-stage clotting assay using
      human plasma. In a THP-1 monocytic hypercoagulation model, a 4-h exposure to
      bacterial endotoxin or Ca(2+) ionophore A23187, respectively, resulted in a 5- or
      10-fold enhancement in monocytic tissue factor (mTF) procoagulation. mTF
      hypercoagulation was offset by PEI included in the assay mixture. PEI showed the
      potential to arrest mTF hypercoagulation with IC(50) around 1.2 nM. Using a
      chromogenic assay to dissect the extrinsic pathway, we further assessed whether
      PEI has any effect on other clotting factors. PEI was not an inhibitor for either
      FVIIa or FXa, having no effect on not only the amidolytic but also their
      corresponding functionally catalytic activities. Although PEI upregulated TF
      dependent FVII activation under the low-salt condition, the effective downstream
      inhibition of fibrin formation readily abolished and overrode the upstream
      enhancement, demonstrating the overall anticoagulation. PEI could present a new
      class of anticoagulant.

PMID- 12801520
TI  - Involvement of MAP kinases in TGF-beta-stimulated vascular endothelial growth
      factor synthesis in osteoblasts.
AB  - Transforming growth factor-beta (TGF-beta) reportedly induces vascular
      endothelial growth factor (VEGF) synthesis in osteoblast-like MC3T3-E1 cells. We
      have recently shown that TGF-beta activates p44/p42 mitogen-activated protein
      (MAP) kinase and p38 MAP kinase in these cells. In the present study, we
      investigated the exact mechanism of TGF-beta behind the synthesis of VEGF in
      MC3T3-E1 cells. PD98059 and U-0126, specific inhibitors of MEK, suppressed the
      VEGF synthesis induced by TGF-beta. U-0126 inhibited the TGF-beta-induced p44/p42
      MAP kinase phosphorylation. SB203580 and PD169316, inhibitors of p38 MAP kinase,
      reduced the TGF-beta-stimulated VEGF synthesis. SB202474, a negative control for
      p38 MAP kinase inhibitor, did not affect the VEGF synthesis. A combination with
      PD98059 and SB203580 almost completely suppressed the TGF-beta-induced VEGF
      synthesis. Retinoic acid, which alone failed to affect VEGF synthesis, markedly
      enhanced the VEGF synthesis stimulated by TGF-beta. Retinoic acid enhanced the
      TGF-beta-increased levels of VEGF mRNA. The amplifications by retinoic acid of
      TGF-beta-increased VEGF synthesis and levels of VEGF mRNA were reduced by PD98059
      or SB203580. The combination of PD98059 and SB203580 almost completely suppressed
      the enhancement by retinoic acid of VEGF synthesis induced by TGF-beta. Taken
      together, our results strongly suggest that both p44/p42 MAP kinase and p38 MAP
      kinase take part in TGF-beta-stimulated VEGF synthesis in osteoblasts, and that
      retinoic acid upregulates the VEGF synthesis.

PMID- 12801521
TI  - Epigallocatechin-3-gallate binding to MMP-2 inhibits gelatinolytic activity
      without influencing the attachment to extracellular matrix proteins but enhances
      MMP-2 binding to TIMP-2.
AB  - Although epigallocatechin-3-gallate (EGCg), a dominant component of green tea
      catechins, has been demonstrated to have anti-gelatinase properties, the
      molecular mechanisms by which EGCg blocks gelatinolytic activities remain
      unknown. We investigated whether EGCg may affect matrix metalloproteinase-2 (MMP
      2) binding to native and denatured-type I collagen, and binding to the tissue
      inhibitor of metalloproteinase-2 (TIMP-2). Here, we report that EGCg forms a
      reversible complex with MMP-2, resulting in the inhibition of gelatinolytic
      activity of MMP-2. EGCg had no effect on the MMP-2 binding to immobilized native
      and denatured-type I collagen, but significantly enhanced pro- and activated MMP
      2 binding to TIMP-2, as assessed by immunoprecipitation. These findings provide a
      new understanding of the molecular mechanisms underlying the inhibitory effect of
      EGCg on the gelatinolytic activity of MMP-2.

PMID- 12801522
TI  - S-nitrosylation of thioredoxin mediates activation of apoptosis signal-regulating
      kinase 1.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) was recently discovered as a typical
      member of the mitogen-activated protein (MAP) kinase kinase kinase family, which
      induces apoptosis by activation of c-Jun-N-terminal kinase/p38 MAP kinase
      pathways. In normal cells ASK1 is directly inhibited by thioredoxin (Trx), a 12
      kDa protein ubiquitously expressed in all living cells, which has a variety of
      biological functions related to cell proliferation and apoptosis. Here we found
      that purified Trx is sensitive to S-nitrosylation. Stimulation of HEK-293 cells
      with S-nitrosoglutathione (GSNO) for 2, 4, 8, and 16h also caused Trx S
      nitrosylation, which showed straight correlation with ASK1 activation based on
      Western blot detection of the enzyme, immunoprecipitation assay, and measurement
      of its catalytic activity. These results suggest that S-nitrosylation of Trx
      induces ASK1 activation. Treatment of cells with N-acetyl-cysteine for 2h after
      8h of pretreatment with GSNO caused an increase in glutathione and nullified ASK1
      activation.

PMID- 12801523
TI  - Malignant hematopoietic cell lines: in vitro models for the study of mast cell
      leukemia.
AB  - Mast cells are multifunctional hematopoietic cells producing various
      proinflammatory mediators. They arise in the bone marrow from CD34+ myeloid
      progenitors under the influence of stem cell factor but reside extravascular in
      the tissues. Mastocytosis which is a rare disorder encompasses a heterogeneous
      group of entities characterized by abnormal proliferation and accumulation of
      mast cells, including mast cell leukemia. Progress in understanding the
      (patho)biology of mast cells has been hindered by the lack of genuine model
      systems, such as continuous cell lines. Now the two in vitro models HMC-1 and LAD
      1/2 are available. Cell line HMC-1 was published in 1988; the sister cell lines
      LAD 1 and LAD 2 have been established in 2000. These cell lines were all derived
      from patients with mast cell leukemia-sarcoma. The cell lines have been properly
      authenticated; their immunophenotypic, cytogenetic, molecular, and functional
      features have been described in detail. Taken together, these cell lines
      reproduce faithfully most or all of the characteristics of primary normal or
      malignant cells in so far as these are known. Interest in this rare but
      nevertheless remarkable cell type should gain momentum with the availability of
      model systems.

PMID- 12801524
TI  - Characterization of novel stem cell factor responsive human mast cell lines LAD 1
      and 2 established from a patient with mast cell sarcoma/leukemia; activation
      following aggregation of FcepsilonRI or FcgammaRI.
AB  - Two novel stem cell factor (SCF) dependent human mast cell lines, designated LAD
      1 and 2, were established from bone marrow aspirates from a patient with mast
      cell sarcoma/leukemia. LAD 1 and 2 cells have the ultrastructural features of
      human mast cells, and express FcepsilonRI, CD4, 9, 13, 14, 22, 31, 32, 45, 64,
      71, 103, 117, 132, CXCR4 (CD184), CCR5 (CD195); and intracytoplasmic histamine,
      tryptase and chymase. LAD 1 and 2 do not exhibit activating mutations at codon
      816 of c-kit. Both LAD 1 and 2 release beta-hexosaminidase following FcepsilonRI
      or FcgammaRI aggregation. The availability of these cell lines offers an
      unparalleled circumstance to examine the biology of human mast cells.

PMID- 12801525
TI  - Regulation of PPAR-gamma gene in human promyelocytic HL-60 cell line.
AB  - The present study employed human promyelocytic cell line, HL-60, as an archetype
      model to understand the role of cholesterol receptors (Receptor-C(k) and
      oxysterol-specific receptor-transcription factor LxR-alpha) in the regulation of
      PPAR-gamma gene recognized to control cellular differentiation and apoptosis.
      Such a study revealed that Receptor "C(k)"-dependent signalling pathway not only
      regulates PPAR-gamma gene transcription but also provides ligands for the
      activation of this nuclear receptor superfamily of transcription factors that
      control hematopoiesis. Based upon these and our earlier results, we propose a
      molecular cross-talk pathway between cholesterol-specific cell surface Receptor
      C(k) and nuclear receptors (LxR-alpha and PPAR-gamma), which may add a new
      dimension in the understanding and control of leukemogenesis.

PMID- 12801526
TI  - Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding
      partner for the p70S6 serine/threonine kinase.
AB  - p70S6K is an intracellular serine/threonine kinase that mediates cell cycle
      progression and gene transcription. Immunofluorescent staining shows in factor
      dependent hematopoietic M-07e cells that p70S6K is localized both in the cytosol
      and, after cytokine stimulation, also in the nucleus. We hypothesized that the
      p70S6K might interact with a transcription factor in the nucleus or with other
      proteins in the cytosol besides the S6 protein. By screening a yeast two-hybrid
      HeLa cDNA library with full-length p70S6K cDNA as bait, we identified tumor
      necrosis factor receptor-associated factor (TRAF) 4 as a new binding partner for
      this kinase. TRAF4 is a member of the TRAF family of putative signal-transducing
      proteins. Members of this family are capable of negatively regulating apoptotic
      pathways by inducing the expression of genes that promote cell survival.
      Immunoprecipitation experiments showed that stimulation of receptors of the tumor
      necrosis factor (TNF) family induced the formation of TRAF4/p70S6K complexes.
      Transfection studies showed that TRAF4 functions in p70S6K activation: TNF
      induced phosphorylation of S6, the main intracellular substrate of the kinase, in
      cells stably expressing TRAF4, but not in TRAF4-negative cells. In addition to
      its role in p70S6K activation, we postulate an anti-apoptotic role for TRAF4,
      because the agonistic anti-Fas antibody CH-11 induced apoptosis in untransfected
      HEK-293 cells, but not in TRAF4-expressing HEK-293 cells. IN CONCLUSION: (i) TNF
      receptor activation leads to activation of the p70S6K; (ii) TRAF4 is a mediator
      in this TNF-induced signaling pathway; and (iii) TRAF4 inhibits Fas-induced
      apoptosis.

PMID- 12801527
TI  - In vitro thymidine kinase/ganciclovir-based suicide gene therapy using
      replication defective herpes simplex virus-1 against leukemic B-cell malignancies
      (MCL, HCL, B-CLL).
AB  - A replication defective herpes simplex virus-1 was evaluated as a therapeutic
      vector. Mantle cell lymphoma (MCL), hairy cell leukemia (HCL), and B-cell chronic
      lymphocytic leukemia (B-CLL) were chosen because leukemic cells were collectable
      from peripheral bloods in these diseases. Cells from six MCL, one HCL, and nine B
      CLL were infected in vitro with T0Z.1 at 3 multiplicity of infection (MOI).
      Herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV)-mediated suicide
      gene therapy showed 14.7% of mean tumor killing against leukemic B-cell
      malignancies. The mean tumor-killing effects were 8.7 and 17.1% in MCL and B-CLL,
      respectively. The effect against HCL was 29%. The study indicates that herpes
      simplex virus (HSV)-based gene therapy might be an effective strategy.

PMID- 12801528
TI  - Adenovirus-mediated gene therapy with an antiangiogenic fragment of
      thrombospondin-1 inhibits human leukemia xenograft growth in nude mice.
AB  - Recent investigations support the idea that angiogenesis is involved in the
      pathophysiology of leukemia. Within a given microenvironment, the angiogenic
      response is regulated by a delicate balance of angiogenesis inducers and
      inhibitors. Thrombospondin-1 (TSP-1) is a multifunctional extracellular
      glycoprotein showing angiostatic properties in multiple in vitro and in vivo
      assays. Interestingly, there is also proangiogenic domain in this complex
      molecule. Development of TSP-1 as an antiangiogenic drug has been hindered by
      multiplicity of its functional effects, difficulties in its production and its
      poor pharmacokinetics. The aim of the present study was to establish a
      recombinant adenovirus (ADV.TSP-1(f)) expressing antiangiogenic fragment of TSP-1
      (TSP-1(f)), and to determine the feasibility for use of the adenovirally
      expressed TSP-1(f) in leukemia gene therapy. The results of this investigation
      showed that TSP-1(f) was expressed efficiently in adenovirus-transduced human
      myelogenous leukemia K562 cells. Compared to the controls, although there was
      almost no effect on proliferation of K562 cells in vitro, adenovirus-mediated TSP
      1(f) transduction inhibited the growth of K562 xenografts dramatically.
      Furthermore, the microvessel density (MVD) was much lower in the ADV.TSP-1(f)
      treated tumors compared to the controls. These data support the use of in vivo
      gene delivery approach to produce antiangiogenic fragment of TSP-1 for leukemia
      therapy.

PMID- 12801529
TI  - Involvement of protein phosphatase 2A in interferon-alpha-2b-induced apoptosis in
      K562 human chronic myelogenous leukaemia cells.
AB  - Interferon-alpha (IFN-alpha)-2b is known to have antiproliferative effects on
      hematological malignant cells, especially chronic myelogenous leukaemia (CML).
      However, it can induce cytogenetical remissions in a very small percentage of the
      patients. Also during interferon therapy, resistance can emerge in the CML
      clones. K562 is an in vitro model cell line transformed from a Ph positive CML
      patient. It can be induced to differentiate to granulocytic and/or monocytic
      lineages with certain molecules. IFN-alpha-2b generally exerts its effects on CML
      cells by Janus family kinases (Jak/Stat) pathway, mostly through tyrosine kinase
      system. However, there is almost no data on the relevance of serine/threonine
      (Ser/Thr) protein phosphatase (PP) system in the interferon induced signal
      transduction pathways. In this study, we investigated serine/threonine protein
      phosphatases in the IFN-alpha-2b induced K562 cytotoxicity. Trypan blue dye
      exclusion test and MTT assay were utilised for determining cytotoxicity. IC(50)
      of IFN-alpha-2b on K562 cells was found to be 600IU/ml. However, no
      differentiation was determined by analysis of cell surface antigen expressions.
      Serine/threonine protein phosphatase inhibitors calyculin A (Cal A) and okadaic
      acid (OKA) augmented the IFN-alpha-2b induced cytotoxicity. Apoptosis assay by
      the mono-oligonucleosome detection and acridine orange/propidium iodide dye
      revealed marked apoptosis underlying cytotoxicity. Phosphatase enzyme assay
      revealed a gradual increase in protein phosphatase 2A (PP2A) activity during
      interferon induced cytotoxicity. Conversely, immunoblots showed no change in the
      expression of PP2A catalytic and regulatory subunits. In conclusion, PP2A plays a
      role in IFN-alpha-2b induced apoptosis of K562 cells and should be investigated
      as a new window furthermore.

PMID- 12801530
TI  - Molecular monitoring of responses to DLI and DLI + IFN treatment of post-SCT
      relapses in patients with CML.
AB  - We monitored DLI treatment of 13 post-SCT relapses using quantitative competitive
      (QC) RT-PCR for BCR-ABL (sensitivity 10(-5)) and compared responses to DLI alone
      and DLI in combination with interferon-alpha (IFN). Ten relapses (one blast
      crisis, five cytogenetic and four molecular) were treated with DLI+IFN, three
      relapses (one cytogenetic, two molecular) were treated with DLI alone. Except the
      patient treated in blast crisis, who died, all the patients treated with DLI+IFN
      achieved complete molecular remission, with the median time interval of 3.9
      months (range 0.25-10.5 months). None of the three patients treated with DLI
      alone have achieved complete molecular remission up to now, i.e. 32, 45, and 50
      months after DLI. However, in all of them some decrease of BCR-ABL transcript
      level was detected. Although the retrospective analyses did not confirm that IFN
      improved the response to DLI, our results based on sensitive molecular monitoring
      suggest that DLI effect, at least in some patients, is supported by IFN
      administration.

PMID- 12801532
TI  - Flt-3 and c-kit mutation studies in a spectrum of chronic myeloid disorders
      including systemic mast cell disease.
AB  - We screened 115 patients with chronic myeloid disorders (CMD) for known flt-3 and
      c-kit mutations in both the juxtamembrane (JM) and the activation loop (AL)
      domains. None of the patients displayed flt-3 (JM or AL) or c-kit JM mutations.
      However, the c-kit AL (D816V) mutation was detected in 5 of 16 patients with
      systemic mast cell disease (SMCD) but in none of the remaining 99 patients with
      other CMD. In SMCD, the presence of D816V mutation was significantly associated
      with advanced age, an aggressive clinical course, increased bone marrow mast cell
      content, and chronic myelomonocytic leukemia.

PMID- 12801531
TI  - Expression of bone morphogenetic proteins in acute promyelocytic leukemia before
      and after combined all trans-retinoic acid and cytotoxic treatment.
AB  - We investigated the dynamics of bone morphogenetic protein (BMP) and their
      receptor mRNA expression in relation to combined treatment with all trans
      retinoic acid (ATRA) and chemotherapy in four patients with acute promyelocytic
      leukemia (APL). Reverse transcription-polymerase chain reaction (RT-PCR) analysis
      of the bone marrow cells at diagnosis showed strong expression of BMP-2, -4, and 
      7, and their receptors RIA, RIB, and RII, parallel to the expression of
      promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion gene
      transcripts. Therapeutic clearance of the tumor molecular marker corresponded to
      the absence of BMP expression, suggesting the possible role of BMPs as markers of
      the minimal residual disease (MRD) in APL.

PMID- 12801533
TI  - Risk classification at the time of diagnosis differentially affects the level of
      residual disease in children with B-precursor acute lymphoblastic leukemia after
      completion of therapy.
AB  - We have previously reported that children with B-precursor acute lymphoblastic
      leukemia (ALL) who remained in remission after successfully completing therapy
      had leukemia cells detectable by polymerase chain reaction (PCR) (N Engl J Med
      1997;336(5):317-23). These patients were treated by an institutional protocol
      (P89-04) that lacked the post-remission intensification features of the
      contemporary Berlin-Frankfurt-Munster (BFM) based ALL protocols. In this report,
      we compared residual leukemia levels for patients on the P89-04 (n=15) and BFM
      based Children's Cancer Group (CCG) studies (n=23) and for patients stratified
      according to risk group. Our goal was to establish which risk factors correlated
      with level of residual disease. Patients enrolled on the CCG protocols had lower
      levels of residual disease after completion of therapy than the P89-04 patients
      (P<0.019). Patients with high-risk disease also had lower levels of residual
      disease than patients with low risk disease (P<0.0001). Three-way analysis
      including time off treatment, risk group determined by features at presentation,
      and treatment protocol showed that risk group was the only significant
      independent variable (P<0.001).

PMID- 12801534
TI  - The treatment of multiple myeloma with docetaxel (an ECOG study).
AB  - BACKGROUND: Docetaxel has activity against multiple malignancies. In a previous
      ECOG study of untreated patients with multiple myeloma, paclitaxel was found to
      have mild activity, but had excessive toxicity. Docetaxel was evaluated in
      patients with relapsing or refractory multiple myeloma. METHOD: Well-documented
      patients with relapsing or refractory multiple myeloma, who had received no more
      than two prior combination chemotherapy regimens, were treated with docetaxel 75
      mgm(-2) intravenously over 1h every 3 weeks. Patients were evaluated after two
      and four cycles of treatment. Standard ECOG criteria were used to evaluate for
      response and toxicity. RESULTS: The study accrued 31 patients with 28 eligible
      for response and 30 for toxicity analysis. No objective responses (partial or
      complete) were found. One patient died due to pneumonia. The majority of patients
      (80%) developed grade 3-4 granulocytopenia and 23% experienced grade 3-4
      thrombocytopenia. The median number of cycles was three. The median survival was
      9.9 months. CONCLUSION: Docetaxel was inactive in patients with relapsing or
      refractory multiple myeloma. In addition, at 75 mgm(-2) every 3 weeks, there was
      extensive hematological toxicity. It is unlikely that a change in dose or a
      different schedule would significantly improve response, limit toxicity, and
      improve survival in patients with multiple myeloma.

PMID- 12801535
TI  - LRP overexpression in monocytic lineage.
AB  - The failure to chemotherapy is a multi factorial phenomenon and lung resistance
      protein (LRP) overexpression has already been discussed as implicated in drug
      resistance. But its role is still discussed. In 1996, we studied the expression
      of LRP and P170 (MDR) in a series of leukemias, at the time of diagnosis, by
      immunocytochemical (ICC) method. The observation of a strong and unusual
      expression of LRP in acute myeloid leukemia (AML) with monocytic component led us
      to test (for P170 and LRP) a new series of 47 AML with different FAB subtypes.
      The expression of LRP was scored from 1 to 5 in blast cells and monocytes
      separately. We demonstrate that LRP is not correlated with clinical outcome but
      is statistically related to monoblastic leukemias. Code 5 reaction was found in
      10/13 M5 versus the other FAB subtypes (P<10(-3)). The strongest LRP
      overexpression was also found in chronic myelomonocytic leukemia (four cases),
      reactive monocytosis (three cases) and in a dendritic cell line. In conclusion,
      we report that LRP is rather a marker of monocytic lineage than a prognostic
      index for MDR and we suggest that detection of LRP by ICC could be an argument
      for the diagnosis of monoblastic and monocytic leukemias.

PMID- 12801538
TI  - Quality of life in myelofibrosis with myeloid metaplasia: a cross-sectional
      study.

PMID- 12801539
TI  - Structure of the Cryptosporidium parvum microneme: a metabolically and
      osmotically labile apicomplexan organelle.
AB  - From an EM study of thin sections, the rod-like microneme organelles within
      conventionally glutaraldehyde fixed Cryptosporidium parvum sporozoites have been
      shown to undergo a shape change to a more spherical structure when the
      sporozoites age in vitro for a period of approximately 12 to 24 h. This
      correlates with the shape change of intact sporozoites, from motile hence viable
      thin banana-shaped cells to swollen pear-shaped cells, shown by differential
      interference contrast light microscopy of unstained unfixed and glutaraldehyde
      fixed samples, as well as by thin section EM of fixed sporozoites. From
      negatively stained EM specimens of unfixed and fixed sporozoites the cellular
      shape change has been confirmed as has the rod to sphere micronemal shape change.
      Intact micronemes released directly from sporozoites exclude negative stain and
      appear as smooth-surfaced electron transparent particles. Biochemically purified
      rod-shaped C. parvum micronemes are shown to be fragile organelles that
      inevitably undergo variable damage during isolation, storage and subsequent
      specimen preparation for EM study. In the absence of glutaraldehyde fixation,
      damaged micronemes allow the negative stain to enter and loose their contents and
      during storage undergo a rod-to-sphere shape transformation. Glutaraldehyde-fixed
      micronemes maintain the rod shape; intact fixed micronemes still exclude negative
      stain but damaged micronemes reveal a complex quasi-helical arrangement of
      internal protein within the rod-like micronemes. Loss of this internal organized
      structure appears to be responsible for the micronemal shape change. This
      interpretation has been advanced from mutually supportive data obtained from
      cryoelectron microscopy of unstained vitrified samples, conventional air-dry
      negative staining and cryo-negative staining. Attempts to biochemically
      solubilize the micronemal content by lysis and ultrasonication, and separate it
      from the micronemal membranes, have so far met with limited success as the
      internal material tends to remain as a disorganized cluster of particles upon
      release.

PMID- 12801540
TI  - A new method for preparing powders for transmission electron microscopy
      examination.
AB  - In this paper we describe a novel method to prepare powder specimens for
      transmission electron microscopy examination. The powder samples are embedded in
      a metallic matrix by a route based on the plastic flow of a soft metal, using a
      small laboratory type hand driven hydraulic press. The resulting composites are
      processed with the conventional procedure based on grinding polishing and ion
      beam milling. The resulting TEM specimens have a self-supporting structure, good
      thermal and electrical conductivity while showing a well-polished surface
      resulting from the ion milling process. The method can be applied to a large
      variety of samples with sufficiently strong mechanical properties; a few examples
      are reported. The limits, mainly due to the mechanical toughness of the powder,
      are discussed.

PMID- 12801541
TI  - Phase analysis of superconducting polycrystalline MgB(2).
AB  - Superconducting MgB(2) ceramics were prepared and yield superconducting
      transition temperatures of about 39 K. For covering the various length scales on
      which inhomogeneities appear in MgB(2), electron-probe micro-analysis (EPMA) and
      analytical transmission electron microscopy (TEM) were applied for a phase
      analysis. Particularly useful were the preliminary electron spectroscopic imaging
      (ESI) results in the TEM. It could be shown by EPMA that the microstructure
      consists of a Mg-B-O matrix and boron-rich secondary phases of composition close
      to MgB(12). It was unclear in which form oxygen was present in the
      superconducting matrix. By combining the acquisition of B-K and O-K edge jump
      ratio images and energy-dispersive X-ray spectroscopy in the TEM, we could prove
      that the matrix consists of superconducting MgB(2) and MgO. Most of the MgO
      precipitates and grains appear with diameters between 20 and 300 nm. The size
      distribution of MgO was inhomogeneous and oxygen-rich areas of dimensions >1
      microm were also observed. Edge jump ratio images obtained by ESI were analysed
      for determining the signal values and effects of multiple inelastic scattering.

PMID- 12801542
TI  - Redeposition effects in transmission electron microscope specimens of FeAl-WC
      composites prepared using a focused ion beam.
AB  - Artifacts associated with transmission electron microscope (TEM) specimens
      prepared using a focused ion beam (FIB) are not well understood, especially those
      in non-semiconductor materials. In this paper the extent and origins of artifacts
      associated with redeposition of milled material in TEM specimens of a FeAl--WC
      metal matrix composite prepared by FIB were investigated. Cross-sections were
      prepared normal to an initial FIB cut that allowed direct observation of any
      damage layers, which are believed to be associated with both redeposition of
      sputtered material and amorphisation of the surface of the specimen by the ion
      beam. Techniques for the minimisation of redeposition using either final cleaning
      mills at low accelerating voltages or plasma cleaning were also investigated and
      found to be ineffective in removing or reducing these damaged layers. TEM cross
      sections of specimens treated using low energy mills and plasma cleaning, further
      confirmed that these techniques did little to reduce any redeposited or amorphous
      material.

PMID- 12801543
TI  - Small metal nanoparticle recognition using digital image analysis and high
      resolution electron microscopy.
AB  - In this paper, we present a system developed to identify metal nanoparticles at
      different orientations, using digital image processing and analysis. The correct
      identification is important in nanotechnology, where it is possible to build
      structures for different purposes at the nanometric level. The recognition system
      computes automatically different characteristics such as: nanoparticle area,
      polygons, symmetry and molecular arrays (twins) in order to recognize different
      nanostructures. All these characteristics are obtained through the use of
      morphological, texture (co-occurrence matrix) and region analysis. Complexity
      issues, advantages, and results are presented and discussed.

PMID- 12801544
TI  - [The plastic surgeon and the walls: the confinement of surgery].

PMID- 12801545
TI  - [Poland's syndrome: clinic series and thoraco-mammary reconstruction. Report of
      27 cases].
AB  - The authors evaluate the quality of thoraco-mammary reconstructions in Poland's
      syndrome. There was 34 patients in our serie, and 27 were operating between 1982
      and 2001. There was 19 women and 8 men; the mean age was 19 years (9-40 years).
      Because of the clinical variability, the authors propose a classification of the
      malformation's importance in 3 degrees. In our serie, there is 35% of degree I,
      53% of degree II and 12% of degree III. Each patient had an average of 2 general
      anaesthesias (1-6). For the first operation time, men had translation of the
      homolateral latissimus dorsi muscle flap in 25%, and a thoracic prosthese in 75%.
      Women had mammary prosthese in 50%, expansion prosthese in 20%, mammary prosthese
      and thoracic prosthese in 20%, muscle flap in 10%. The same person analysed the
      results in terms: good, middle or bad. The results are good in 67%, middle in
      22%, poor in 11%. In degree 1, the results are always good; in degree II, they
      are good in 59%, middle in 29% and poor in 12%; in degree III, the results are
      good, middle and poor in 33%.

PMID- 12801546
TI  - [Funnel chest: filling technique with deep custom made implant].
AB  - Through 97 patients over 9 years, the authors present a surgical treatment for
      "funnel chest" using custom-made silicone elastomer prothesis which are deeply
      placed, behind muscle and aponevroses. They justify the choice of this simple and
      non invasive technique, by the fact that this deformation is only morphological
      in most cases or even only inaesthetic with exceptional cardiac or pulmonary
      consequences. Patient's motivation being mainly due to psychological disconfort,
      the non invasive aspect of the technique leads them to choose surgery,
      particularly as results are good and complications seldom.

PMID- 12801547
TI  - [Correction of the congenital malformations of the front chest wall by the
      modelling technique of sternochondroplasty: technique and results on a series of
      14 cases].
AB  - In the congenital malformations of the front chest wall showing depression or
      protrusion, the cardiorespiratory disorders are inconstant and often not linked
      with the distortion. On the other hand psychoaffective repercussions are major in
      adolescents and young adults justifying recourse to surgery with morphological
      and aesthetic aiming. The authors present the technique of modelling
      sternochondroplasty by raising with osteosynthesis by slide fastener-handle of
      Martin-Borrelly, applied to the correction of congenital malformation of the
      front chest wall in young adult, both of protrusion (pectus carinatum), of
      thoraxes in funnel (pectus excavatum) types or of mixed types (pectus arcuatum).
      This surgical replanning intervention is carried out by under-mammary way and
      aims at reestablishing a normal anatomy of the front chest wall. It leads to a
      genuine wide sternochondrocostal volet, which is stabilised by a specific,
      multipurpose, adaptable and reliable osteosynthesis equipment. The results
      obtained on a series of 14 cases are good or excellent in 86% of the cases and
      stable over time in the absence of major complications. A good cooperation of the
      patient is essential to obtain a good result in particular via the continuation
      of musculation exercises after assembly consolidation, possibly associated with
      remote mammary plastic surgery in the event of hypoplasia or of associated
      mammary agenesia.

PMID- 12801548
TI  - [Complete chest wall reconstruction after en bloc excisions with Gore
      Tex/Marlex/Flap sandwich. A retrospective study of 14 cases].
AB  - To assess the results of surgical resection and chest wall reconstruction we
      reviewed our experience with the complete chest wall reconstruction after en bloc
      excisions according to an original algorithm based on the location of the
      thoracic defect. The 14 reconstructions were performed by the senior author. We
      found 5 central, 6 lateral and 3 borders locations. In the central locations with
      a total resection of the sternum the reconstruction was realized by Gore-tex's
      mesh in depth, metal hooks (staples) and Marlex's mesh under a musculocutaneous
      flap of coverage. In case of lateral location the reconstruction was realized by
      Gore-tex's mesh covered with a musculocutaneous flap, the borders locations were
      reconstructed by Marlex's mesh and flap of coverage. The histological diagnoses
      were: one desmoid tumor, eight sarcomas, a recurrence of hepatocarcinoma and four
      recurrences of breast cancer. The superficial coverage performed by latissimus
      dorsis flap 12 for cases and rectus abdominis flap for two cases. All the
      patients were able to produce a spontaneous breath after surgery. Two deaths at
      distance and an infection were to regret. On the whole the algorithm of
      reconstruction according to the location of the defect allows a simplification of
      the indications.

PMID- 12801549
TI  - [Surgery of chest wall tumors].
AB  - The treatment of the chest wall tumors are based on the following principles. The
      surgery is the only curative treatment of the disease and the pain. The pre
      operative assessment may find its beneficial only to eliminate the non surgical
      affections, to foresee the peroperative dangers and to prepare the
      reconstruction. The use of more adapted and better supported prosthesis has
      pushed back today the limits of the resections to the possibilities of covering.
      Finally the quality of the result depends more than one multidisciplinary work
      that technical prowess's of only one operator.

PMID- 12801550
TI  - [About the rational use of intrathoracic transfers. Anatomical and surgical bases
      for the selection of twelve different muscular and omental flaps].
AB  - Because of their rich blood supply and of their original detersive and filling
      properties, the muscular pedicled flaps harvested from the trunk or the omental
      flap elevated from the abdomen may be very usefull to treat large defects or
      major septic problems in pleural, pericardic or mediastinal cavities. We here
      describe the main principles to be followed in such intrathoracic reconstructions
      performed in order to control severe mediastinites, aortic prosthetic infections,
      pleural empyemas and broncho-pleural, tracheo-esophageal or broncho-esophageal
      fistulas. In all these circumstances, the muscular or omental flaps which are
      transferred into the chest are selected according to the recipient field and to
      their respective access to the upper, middle and lower portions of the pleural
      space or mediastinum. Twelve different flaps so appear available to achieve the
      adequate reconstruction, filling or coverage of nine distinct topographic sites.
      Their rational use, based on various anatomical guidelines, allows to prevent or
      to cure efficiently 90% of the infectious or fistular complications frequently
      observed in the postoperative course of aggressive, functional or oncological,
      intrathoracic surgical procedures.

PMID- 12801551
TI  - [Plastic surgery procedures in the treatment of mediastinitis in adult].
AB  - Closed vacuum drainage is becoming the standard technique in most early
      postoperative mediastinitis, open wound treatment being only necessary in case of
      failure of the previous technique or in high grade mediastinitis. The
      reconstruction technique to be chosen depends on both resulting wound
      presentation after debridement and thorax morphology. Mediastinal dead space
      obliteration is a "sine qua non" for success often requiring multiple flap
      transposition. Since 1983, reconstructive procedures were carried out in 205
      patients, of them 95 had bilateral pectoralis major turn-over transposition flaps
      on internal pedicules, following internal mammary artery coronary
      revascularisation in 45. Trapezius and latissimus dorsi were the next most used
      flaps. Transposition of the omentum although especially well suited for torpid
      wounds was to often precluded by bad abdominal risk factors. Conservative closed
      drainage salvaged by reconstructive procedures when necessary has greatly
      improved both survival and functional outcome of these patients.

PMID- 12801552
TI  - [Thoracic ballistic traumatisms. Wounding agents and wound ballistic].
AB  - The adequate care of thoracic ballistic traumatisms implies a good preliminary
      knowledge of wounding agents, and of the principles governing lesion-based
      ballistic, in particular the role played by the meeting with an obstacle which
      modifies the ballistic behaviour of the projectile, with worsened wounding
      effects. Authors describe the principal types of involved projectiles and their
      wound profile applied to the thorax, while stressing the need to treat
      systematically the wound and not the weapon, and on the importance of the choice
      of the surgical exploration way of these lesions, which conditions, as from the
      initial stage, the later choices of the parietal closure and rebuilding methods.
      The importance of parietal disrepair is therefore an essential decisional factor
      in the assumption of responsibility and the definition of the therapeutic
      strategy of these casualties.

PMID- 12801554
TI  - Effect of male age on fertility: evidence for the decline in male fertility with
      increasing age.
AB  - OBJECTIVE: To evaluate the effect of men's age on time to pregnancy (TTP) using
      age at the onset of pregnancy attempts, adjusting for the confounding effects of
      women's age, coital frequency, and life-style characteristics. DESIGN:
      Observational study. SETTINGS: Teaching hospital in Hull, United Kingdom.
      PATIENT(S): Two thousand one hundred twelve consecutive pregnant women.
      INTERVENTION(S): A questionnaire inquiring about TTP, contraceptive use,
      pregnancy planning, previous subfertility, previous pregnancies, age, and
      individual life-style characteristics of both partners. MAIN OUTCOME MEASURE(S):
      Time to pregnancy, conception rates, and relative risk of subfecundity for men
      and women's age groups. RESULTS: As with women's age, increasing men's age was
      associated with significantly rising TTP and declining conception rates. A
      fivefold increase in TTP occurred with men's age >45 years. Relative to men <25
      years old, those >45 years were 4.6-fold and 12.5-fold more likely to have had
      TTP of >1 or >2 years. Restricting the analysis to partners of young women
      revealed similar effects of increasing men's age. Women >35 years were 2.2-fold
      more likely to be subfertile than women <25 years. The results were comparable,
      whether age at conception or at the onset of pregnancy attempts was analyzed, and
      they remained unchanged after adjustment for the confounding factors.
      CONCLUSION(S): Evidence for and quantification of the decline in men's fertility
      with increasing age is provided.

PMID- 12801555
TI  - Predictive value of sperm fluorescence in situ hybridization analysis on the
      outcome of preimplantation genetic diagnosis for translocations.
AB  - OBJECTIVE: To determine whether the proportion of abnormal sperm is predictive of
      the proportion of abnormal embryos from couples in which the males are
      translocation carriers. DESIGN: Controlled clinical study. SETTINGS: Private in
      vitro fertilization (IVF) center. PATIENT(S): Eleven cases of reciprocal
      translocation male carriers. INTERVENTION(S): Blood sample and sperm sample
      collection from each male partner. Embryo biopsy of the embryos produced in each
      cycle. MAIN OUTCOME MEASURE(S): Fluorescence in situ hybridization on lymphocyte
      slides to characterize each translocation case, then fluorescent in situ
      hybridization (FISH) with specific probes for each of the sperm samples.
      Preimplantation genetic diagnosis of the translocations in the 11 cases. RESULTS:
      A correlation was found between the percentage of abnormal gametes and the
      percentage of abnormal embryos, and a predictive equation is proposed for this
      relationship: A = -55 + (1.9 x B), where A is the percentage of abnormal embryos
      and B the percentage of abnormal sperm. CONCLUSION(S): The predictive value of
      the sperm analysis was established. Patients with 65% or less chromosomally
      abnormal sperm have a good chance at conceiving; patients with higher rates would
      need to produce 10 or more good quality embryos to have reasonable chances of
      conceiving.

PMID- 12801556
TI  - Relationship between sperm characteristics and hormonal parameters in normal
      couples.
AB  - OBJECTIVE: To examine the relationships between hormone profiles and semen
      analysis measures and fertility in the male partners of presumed normal couples.
      DESIGN: Prospective clinical study. SETTINGS: Healthy volunteers in an academic
      research environment. PATIENT(S): One hundred forty-five reproductive age couples
      without known risk factors for infertility and who had discontinued contraception
      to achieve pregnancy completed this component of this study. Each couple was
      followed for < or =12 menstrual cycles while they attempted to conceive.
      INTERVENTION(S): Semen quality measures for the first ejaculates were obtained at
      the start of the study along with a single blood sample. Levels of FSH, bioactive
      FSH, inhibin B, LH, and T were measured for each man. MAIN OUTCOME MEASURE(S):
      Semen analysis, FSH, inhibin B, LH, T, and clinical pregnancy. RESULTS:
      Significant positive relationships were observed between the two measures of FSH
      as well as between both of the FSH measures and LH. Follicle-stimulating hormone
      as measured by RIA was significantly negatively correlated with inhibin B.
      Inhibin B showed a marginally significant negative correlation with LH, and LH
      and T had a marginally significant positive correlation. Inhibin B increased
      significantly, and both measures of FSH activity showed significant decreases,
      with increasing levels in several semen quality measures. There was no
      significant relationship between the measured hormones and the pregnant and
      nonpregnant groups or time to pregnancy. CONCLUSION(S): These results contribute
      additional information on the utility of reproductive hormone measurements for
      predicting semen quality in couples without known reduced fertility.

PMID- 12801557
TI  - Fertility in men with testicular germ cell tumors.
AB  - OBJECTIVE: To assess the prevalence of fertility or infertility in men before and
      after treatment for unilateral testicular cancer. The results were compared with
      the lifetime prevalence of infertility in the general population (20%-28%).
      DESIGN: Survey. SETTINGS: University referral center for testicular cancer.
      PATIENT(S): Two hundred twenty-six patients treated for testicular cancer.
      INTERVENTION(S): Questionnaire on fertility and fertility-related factors before
      and after treatment of disease. MAIN OUTCOME MEASURE(S): Prevalence of fertility
      before and after treatment for testicular cancer. RESULT(S): Before the cancer
      was diagnosed, 79 (66%) of 120 couples who attempted to conceive succeeded within
      1 year. After treatment, 38 (43%) of 88 couples conceived within 1 year. Seven
      couples used cryopreserved sperm to conceive a child after treatment. The
      different treatment modalities did not significantly influence the outcome of
      patients' wish for children. Congenital malformations were recorded in
      approximately 4% of the children born before or after treatment. CONCLUSION(S):
      Although the majority of the patients with testicular cancer have a fulfilled
      wish with regard to children, it seems to be more difficult to father a child
      after treatment compared with the case in the general population. Because it is
      not possible to predict which patient will have fertility problems after
      treatment, cryopreservation should be offered to every testicular cancer patient.
      An increased risk for congenital malformations was not observed.

PMID- 12801559
TI  - Relationship between semen cultures, leukospermia, and semen analysis in men
      undergoing fertility evaluation.
AB  - OBJECTIVE: To determine the correlation between semen cultures, semen Gram
      stains, leukospermia, and semen analysis parameters in asymptomatic men
      undergoing fertility evaluation. DESIGN: Prospective clinical study. SETTINGS:
      Infertility clinic at a university teaching hospital. PATIENT(S): Two hundred
      ninety-nine asymptomatic men undergoing fertility evaluation. INTERVENTION(S):
      After an antibacterial skin preparation, all men gave semen specimens for
      culture, Gram stains, semen analysis, and assessment for leukospermia. MAIN
      OUTCOME MEASURE(S): A comparison of the presence or absence of bacteriospermia,
      the specific bacterial isolate, the quantity of bacteriospermia, the presence or
      absence of leukospermia, and semen analysis parameters. RESULT(S): The presence
      or absence of bacteriospermia or leukospermia did not correlate with each other.
      Leukospermia did not correlate with semen parameters. Staphylococcus species was
      the most common isolate (25.4% of all patients) and did not correlate with semen
      parameters or leukospermia. Streptococcus viridans (15.4% of all patients) and
      Enterococcus faecalis (7.4% of all patients) were the next most common isolates
      and were associated with statistically significantly poorer semen quality.
      CONCLUSION(S): Leukospermia is a poor marker for either bacteriospermia or
      impaired semen quality. Staphylococcus species are commonly isolated but appear
      to be innocuous. Streptococcus viridans and Enterococcus faecalis are associated
      with poorer semen quality and may warrant treatment.

PMID- 12801558
TI  - Male smokers have a decreased success rate for in vitro fertilization and
      intracytoplasmic sperm injection.
AB  - OBJECTIVE: Smoking by one or both partners can adversely affect IVF outcome. We
      investigated whether smoking may also play a role in the success rate of
      intracytoplasmic sperm injection (ICSI), in which initial steps of fertilization
      are bypassed. DESIGN: Three hundred one couples (ICSI: 153, IVF: 148)
      participated in 415 treatment cycles (ICSI: 202, IVF: 213). One hundred thirty
      nine men were habitual smokers (ICSI: 71, IVF: 68). Seventy-seven women were
      smokers (ICSI: 41, IVF: 36). Multiple nominal regression analyses of various
      steps of assisted reproduction included smoking status, age, semen parameters,
      and number of embryos transferred. SETTINGS: Reproductive and andrology unit of
      the university. PATIENT(S): Three hundred one couples seeking fertility
      treatment. INTERVENTION(S): Assisted reproduction by in vitro fertilization (IVF)
      or ICSI. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Intracytoplasmic
      sperm injection success (clinical pregnancy) in women with smoking male partners
      was 22% and was 38% with nonsmoking partners. Similar results were seen for IVF,
      with 18% vs. 32%. Multinominal logistic regression analysis revealed smoking in
      men to be a significant predictor of ICSI outcome, along with female age and the
      number of embryos transferred, whereas clinical pregnancies after IVF were
      dependent on smoking in men, number of embryos transferred, sperm motility, and
      female age. Female smoking influenced the number of oocytes retrieved and the
      fertilization rate of oocytes in IVF but not in ICSI. The odds ratio for failure
      of ICSI for male smokers in comparison to male nonsmokers was 2.95 (IVF: 2.65).
      CONCLUSION(S): Smoking by males decreases the success rates of assisted
      reproduction procedures, not only in IVF, but also in ICSI. Apart from putative
      adverse effects during fertilization, altered DNA in spermatozoa might hamper
      development of the embryo.

PMID- 12801560
TI  - Y chromosome microdeletions in infertile men with cryptorchidism.
AB  - OBJECTIVE: To determine whether cryptorchidism associated with azoospermia or
      oligozoospermia may be due to microdeletions of the Y chromosome. DESIGN:
      Controlled clinical study. SETTINGS: Division of Medical Genetics and the
      Andrology Centre, Department of Obstetrics and Gynecology, University Medical
      Center, Ljubljana. PATIENT(S): Ninety men from infertile couples (36
      azoospermics, 35 oligozoospermics, and 19 normozoospermics) with a medical
      history of cryptorchidism. Nineteen excryptorchid patients with cryptorchidism
      and Y chromosome microdeletions among 3099 patients from 14 publications.
      INTERVENTION(S): Collection of semen and blood samples. MAIN OUTCOME MEASURE(S):
      Medical history, testicular volume, sperm characteristics, serum FSH levels,
      testicular histology, presence or absence of Y chromosome microdeletions,
      including all known Y chromosome genes/gene families in the azoospermia factor
      (AZF) region. RESULT(S): Deletions of the Y chromosome were found in 2 out of 71
      cryptorchid patients with azoospermia or oligozoospermia (2.8%). The literature
      review showed that the incidence of microdeletions in infertile patients with
      cryptorchidism is lower in comparison with the general population of infertile
      men (4.9% vs. 8.1%), and that the frequency of cryptorchidism in patients with Y
      chromosome deletions (6 out of 103, 5.8%) is significantly lower in comparison to
      infertile patients without deletions (178 out of 1141, 15.6%). CONCLUSION(S): No
      causal relation exists between Y chromosome microdeletions and cryptorchidism.

PMID- 12801561
TI  - Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the
      semen of men attending an infertility clinic.
AB  - OBJECTIVE: To investigate the prevalence of herpes simplex virus (HSV),
      cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in the semen of men with
      fertility problems. DESIGN: A descriptive clinical study. SETTINGS: Outpatient
      infertility clinic of a private hospital. PATIENT(S): One hundred thirteen men
      attending an infertility clinic in Athens. INTERVENTION(S): Semen samples were
      collected by masturbation. MAIN OUTCOME MEASURE(S): Detection of HSV, CMV, and
      EBV in semen by a nested polymerase chain reaction technique. Complete spermogram
      including sperm count, motility, pH, viscosity, and morphology. RESULT(S): Viral
      DNA was detected by the nested polymerase chain reaction technique in 64 (56.6%)
      of 113 semen samples. Specifically, HSV DNA was detected in 56 (49.5%) semen
      samples, EBV DNA in 19 (16.8%) semen samples, and CMV DNA in 8 (7.1%) semen
      samples. HSV was significantly related to low sperm count and poor motility. In
      contrast, CMV and EBV did not show any association with sperm concentration and
      motility. CONCLUSION(S): Herpes simplex virus seems to play a significant role in
      male infertility, and its early detection by the nested polymerase chain reaction
      technique will permit successful antiviral therapy to increase the possibility
      for fertility restoration and long-term protection of the sperm quality. Finally,
      the detection of herpes viruses within semen will allow better control of the
      transmission of these viruses.

PMID- 12801562
TI  - Psychosocial factors discriminate oligozoospermic from normozoospermic men.
AB  - OBJECTIVE: To compare the profile of psychosocial variables in a group of
      oligozoospermic and normozoospermic men for assessing the hypothesis of a
      relationship between impaired seminal status and psychosocial factors. DESIGN:
      Double-blind investigation of the psychosocial differences between
      oligozoospermics and normozoospermics. SETTINGS: Healthy volunteers in a clinical
      environment. PATIENT(S): Two hundred eighty men attending their first seminal
      examination. INTERVENTION(S): We selected 37 oligozoospermic patients on the
      basis of sperm concentration and 37 normozoospermic controls for comparison.
      OUTCOME MEASURE(S): Differences in alexithymia (difficulty identifying feelings,
      difficulty describing feelings, externally oriented thinking), personality traits
      (extroversion, neuroticism, psychoticism), and coping style toward stressors
      (task-oriented coping, emotion-oriented coping, avoidance-oriented coping) were
      assessed in the two groups. RESULT(S): Wilk's Lambda (.79) of the discriminant
      analysis showed a statistically significant difference between the two groups.
      The following variables met the inclusion criterion in the discriminant function:
      psychoticism and difficulty describing feeling. This analysis also showed a high
      probability of correct classification of oligozoospermic men on the basis of the
      psychosocial variables. CONCLUSION(S): The relationship between psychosocial
      variables and seminal status has been confirmed in a group of oligozoospermic and
      normozoospermic men.

PMID- 12801563
TI  - Total antioxidant capacity in patients with varicoceles.
AB  - OBJECTIVE: To explore a possible molecular defect linked to infertility, studying
      total antioxidant capacity (TAC) of seminal plasma in varicocele (VAR). DESIGN:
      Case-series study. SETTINGS: Volunteers in an academic research environment and
      out-patients in clinical service. PATIENT(S): Twenty-five VAR patients (9
      oligospermic and 16 normospermic) vs 24 non-VAR controls (7 subjects with
      idiopathic oligospermia and 17 normospermic subjects). INTERVENTION(S):
      Evaluation of seminal plasma TAC. MAIN OUTCOME MEASURE(S): TAC was measured using
      myoglobin, as a source of radicals, which interact with a chromogen 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulphonate) (ABTS), whose radical cation is
      spectroscopically detectable. The latency phase (Lag) in the accumulation of ABTS
      cation is proportional to antioxidant concentration. RESULT(S): Lag showed
      significantly greater values in the all VAR patients vs non-VAR subjects.
      Oligospermic-VAR patients showed the greatest values. Lag and sperm motility
      significantly correlated in VAR normospermic patients. Follicle-stimulating
      hormone (FSH) showed significant inverse association with Lag in same group.
      CONCLUSION(S): The augmented Lag values could indicate an ineffective utilization
      of antioxidants in oligospermic-VAR, while in normo-VAR the direct correlation
      between TAC and motility suggest a potential protective role toward sperm
      motility. In the same group, the inverse correlation with FSH suggests that
      greater FSH levels induce a better utilization of antioxidants by spermatozoa.

PMID- 12801564
TI  - Metal chelators change the human sperm motility pattern.
AB  - OBJECTIVE: To investigate the influence of zinc on the generation of motility.
      DESIGN: Prospective study. SETTINGS: Outpatient clinic of the Center of
      Dermatology and Andrology. PATIENT(S): Seventy-three patients and 10 sperm
      donors. INTERVENTION(S): Motile spermatozoa were isolated by swim-up and
      incubated for 1, 2, 4 or 6 hours with DL-penicillamine, 2,3-dimercaptopropan-1
      sulfonate, and meso-2,3-dimercapto-succinimic acid at concentrations of 1, 10,
      and 100 micro mol/L. MAIN OUTCOME MEASURE(S): Motility was analyzed by means of
      computer-assisted semen analysis (CASA). RESULT(S): Significant dose-dependent
      changes in nonlinear motility, progressive motility, and velocity straight line
      (VSL) were observed. After only 1 hour of incubation, nonlinear motility
      decreased, and progressive motility and VSL increased. The percentage of immotile
      spermatozoa was not affected. Time-dependent changes in motility were observed on
      a significantly higher or lower level as compared to the control. Comparing the
      chelators after 2 hours revealed that DL-penicillamine showed the strongest
      effect on the sperm. CONCLUSION(S): The results imply that chelators can
      eliminate at least some part of the zinc from the flagellum. This zinc
      elimination appears to lead to comparable changes of the outer dense fibers as
      seen in vivo during epididymal maturation, finally resulting in improved
      motility.

PMID- 12801566
TI  - Negative effects of increased sperm DNA damage in relation to seminal oxidative
      stress in men with idiopathic and male factor infertility.
AB  - OBJECTIVE: To examine the effects of increased sperm DNA damage in relation to
      seminal oxidative stress in men with idiopathic and male factor infertility.
      Prospective study. SETTINGS: Infertility clinic at a tertiary care academic
      institution. PATIENT(S): Ninety-two infertile men with normal female partners.
      Sixteen fertile donors served as the control group. INTERVENTION(S): Standard
      semen analysis and assessment of levels of seminal oxidative stress. Assisted
      reproductive techniques in 33 of the 92 patients (IUI [n = 19], IVF [n = 10], and
      intracytoplasmic sperm injection [n = 4]). MAIN OUTCOME MEASURE(S): Sperm DNA
      damage by sperm chromatin structure assay. Results were expressed as DNA
      fragmentation index. RESULT(S): Patients were classified as having either
      idiopathic (n = 23) or male factor infertility (n = 69). Patients with idiopathic
      and male factor infertility had significantly higher DNA fragmentation index and
      oxidative stress compared with the case of fertile donors. A clinical pregnancy
      was achieved in 9 (27%) of 33 patients with assisted reproductive techniques.
      Significantly higher DNA fragmentation index and oxidative stress were found in
      men who failed to initiate a pregnancy after assisted reproductive techniques (n
      = 24), compared with the cases of those who succeeded and of the fertile donors.
      DNA fragmentation index was correlated positively with oxidative stress (r =
      0.27), and negatively with fertilization (r = -0.70) and embryo quality (r = 
      0.70). CONCLUSION(S): Sperm DNA damage is significantly increased in men with
      idiopathic and male factor infertility and in men who failed to initiate a
      pregnancy after assisted reproductive techniques. Such an increase may be related
      to high levels of seminal oxidative stress.

PMID- 12801565
TI  - Alpha 6 beta 1 Integrin is a potential clinical marker for evaluating sperm
      quality in men.
AB  - OBJECTIVE: To determine the clinical significance of alpha6beta1 integrin in
      human spermatozoa. DESIGN: Prospective case-controlled study. SETTINGS: Hospital
      infertility clinic in India. PATIENT(S): Sixty-two men undergoing evaluation for
      infertility and 20 healthy, proven-fertile controls were selected.
      INTERVENTION(S): Role of alpha6beta1integrin in sperm quality evaluation was
      determined using semen analysis, cell ELISA, flow cytometry, and in vitro sperm
      egg binding. MAIN OUTCOME MEASURE(S): Determination of sperm-associated
      alpha6beta1 integrin may help in assessing the quality of the human spermatozoa.
      RESULT(S): Expression of alpha6beta1 integrin was significantly low in the
      spermatozoa obtained from subfertile men. Only 35%-40% of spermatozoa from
      fertile men showed a positive reaction to alpha6beta1 antibody. The samples with
      high rate of acrosomal reaction showed a good expression of alpha6beta1 and
      maximum binding to oocyte in an in vitro binding assay. CONCLUSION(S):
      alpha6beta1 Integrin may be used as a clinical marker to evaluate sperm quality.

PMID- 12801567
TI  - Identification of human sperm proteins involved in the interaction with
      homologous zona pellucida.
AB  - OBJECTIVE: To identify human sperm proteins involved in homologous zona pellucida
      (ZP) interaction. DESIGN: Prospective study. SETTINGS: Basic research laboratory.
      PATIENT(S): Semen samples from normozoospermic donors, tissue sections from
      surgical pieces, and ZP from nonfertilized oocytes. INTERVENTION(S): Antibodies
      for sperm proteins (HSE; high salt extract) were developed (anti-HSE) and
      partially characterized. Participation of sperm proteins on ZP-interaction was
      tested with the hemizona assay (HZA). Antigens were immunolocalized in sperm and
      tissues. MAIN OUTCOME MEASURE(S): Sperm and tissue immunostaining; Western
      blotting; and number of sperm bound to the ZP. RESULT(S): Anti-HSE antibodies
      recognized several polypeptides in HSE (9 to 200 kd). Specific antibodies for 49
      and 66 kd proteins (p49, p66) were obtained. Both (anti-p49 and anti-p66) stained
      the head of ejaculated and capacitated sperm. In the HZA, sperm preincubation
      with a mixture of anti-p49 and anti-p66 (100 micro g/mL) resulted in a decrease
      in the number of spermatozoa bound to the ZP. Presence of p66 (10 micro g/mL)
      inhibited sperm-ZP interaction. In contrast, p49 did not alter sperm binding to
      the ZP. Immunohistochemical analysis showed that p66 is present in the
      epididymis. No staining was observed in testicular sections. CONCLUSION(S): We
      found that p66 is an epididymal protein that participates in human sperm
      interaction with homologous ZP.

PMID- 12801568
TI  - Hyaluronic acid binding by human sperm indicates cellular maturity, viability,
      and unreacted acrosomal status.
AB  - OBJECTIVE: To test, both in semen and washed-sperm fractions, whether hyaluronic
      acid (HA) binding is restricted to sperm that have completed cellular maturation.
      DESIGN: Comparisons of sperm in semen and in HA-bound sperm fractions. SETTINGS:
      University-based diagnostic and research andrology laboratory. PATIENT(S): Semen
      samples originated in men being tested for infertility. INTERVENTION(S): The
      attributes of sperm maturity were tested by immunocytochemistry with creatine
      kinase and HspA2 antisera (highlights cytoplasmic retention in diminished
      maturity sperm), aniline blue chromatin staining (detects persistent histones),
      pisum sativum lectin staining (reveals acrosomal integrity), and the FertiLight
      viability kit (highlights viable and nonviable sperm). RESULT(S): All markers of
      sperm maturity and immaturity supported the hypothesis that HA-bound sperm are
      mature. Nonbinding sperm exhibited cytoplasmic and nuclear properties of
      diminished maturity. The acrosomal status of HA-bound sperm was either unreacted
      or slightly capacitated, but not acrosome reacted. Only viable sperm exhibited HA
      binding. CONCLUSION(S): Sperm that are able to bind to HA are mature and have
      completed the spermiogenetic processes of sperm plasma membrane remodeling,
      cytoplasmic extrusion, and nuclear histone-protamine replacement. Hyaluronic acid
      bound sperm show unreacted acrosomes. These studies provide further insights into
      the relationship between spermiogenesis and sperm function.

PMID- 12801569
TI  - Efficacy and pregnancy outcome of two methods of semen preparation for
      intrauterine insemination: a prospective randomized study.
AB  - OBJECTIVE: To examine pregnancy outcome with two methods of semen preparation for
      intrauterine insemination (IUI). DESIGN: Prospective and randomized study.
      SETTINGS: Academic tertiary center. PATIENT(S): Three hundred eleven couples
      undergoing 676 consecutive cycles of assisted conception using IUI.
      INTERVENTION(S): Semen samples collected for IUI were randomized to wash only or
      density gradient centrifugation (DGC) processing. MAIN OUTCOME MEASURE(S):
      Various prepreparation and postpreparation semen parameters were used for IUI.
      The influence of the method of semen processing, and impact of various semen
      parameters and female factors on pregnancy were examined by receiver operating
      characteristics (ROC) curves, logistic regression, and life table analysis.
      RESULT(S): Of the 676 cycles, 88 resulted in conception leading to an overall
      clinical pregnancy rate of 13.0% per cycle and 28.3% per patient with a
      miscarriage rate of 34.0%. Eighty-eight percent of pregnancies occurred in the
      first three cycles of IUI and 95.5% within the first four cycles. The pregnancy
      rate for wash only was 11.6% (37 of 319) and the rate for DGC was 14.3% (51 of
      356). However, in samples with <22 million motile sperm in the inseminate,
      pregnancy rates were 4% for wash and 18% for DGC. The woman's age for both
      methods and the percentage of sperm in the original semen with a velocity of > or
      =80 micro m/s for the wash method influenced pregnancy outcome. CONCLUSION(S):
      Although samples with an acceptable number of motile sperm can be processed
      efficiently by wash only, poor quality semen samples should be processed using
      DGC.

PMID- 12801570
TI  - Sperm recovering efficiency, a mathematical model, is designed to objectively
      evaluate semen processing techniques and methods.
AB  - OBJECTIVE: To propose the sperm recovering efficiency (SRE) model, an equation
      that can be used to objectively quantify the technical skill of individual
      operators processing semen specimens in an andrology laboratory. Additionally,
      this equation can be used to compare different semen processing methods and
      protocols. This model integrates the semen parameters of initial sperm
      concentration, motility, morphology, and final sperm recovery to produce a unique
      number that can be used to compare results. DESIGN: A theoretical and deductive
      analysis. SETTINGS: Private assisted reproductive units. PATIENT(S): None.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Motile progressive and
      morphologically normal sperm concentration. RESULT(S): The SRE is a mathematical
      equation that can be used to compare initial semen parameters to postpreparation
      concentration, progressive motility, and normal morphology. The result is a
      number between 0 and 1. The model constitutes an objective means for determining
      the efficiency of a particular technique (gradients, migration, or filtration) or
      to set up the best conditions for that technique (time, gravities, medium volume,
      and sample volume). Additionally, the SRE permits comparisons between different
      operators, media, lots, laboratory conditions, treatments, and sample parameters.
      It can be used as a tool in laboratory quality control and for multicenter
      studies. CONCLUSION(S): Sperm recovering efficiency (SRE) is an objective method
      to compare the results of semen processing techniques.

PMID- 12801571
TI  - Monitoring technologist reading skills in a sperm morphology quality control
      program.
AB  - OBJECTIVE: The value of sperm morphology as a predictor of a man's fertilizing
      potential has often been challenged because of different classification systems
      used to distinguish between normal and abnormal spermatozoa. The study aimed to
      monitor the reading skills of 53 laboratory technologists who are enrolled in a
      continuous quality control program for sperm morphology assessment. DESIGN:
      Prospective analytical study. SETTINGS: Academic hospital and academic
      institution setting. PATIENT(S): Sperm samples from the sperm donor program and
      andrology technicians from sub-Saharan Africa. INTERVENTION(S): Papanicolaou
      stained sperm slides were prepared and shipped on a quarterly basis to
      participating laboratories. Papanicolaou-prestained sperm morphology slides were
      used as test material for 21 months. MAIN OUTCOME MEASURE(S): Percentage normal
      spermatozoa.A new statistical model was developed to record reading skills of the
      participating technicians. Reading skills were classified as marginal (5.7% of
      cases), good (11.3% of cases), and excellent (83% of cases). RESULT(S):
      Participants maintained their morphological reading skills and agreed with the
      reference laboratory by not exceeding a SD limit of 0.2 to set stringent
      standards for the program. CONCLUSION(S): Technician proficiency can be monitored
      using the results of a quality control program. A continuous quality control
      program can be initiated only after intensive training, because baseline values
      at the onset of the quality control program serves as an internal reference
      value.

PMID- 12801572
TI  - An increased incidence of autosomal aneuploidies in spermatozoa from a patient
      with Klinefelter's syndrome.
AB  - OBJECTIVE: To determine whether there is an increased incidence of autosomal
      aneuploidies in spermatozoa from a subject with nonmosaic Klinefelter's syndrome.
      DESIGN: Analysis of sperm nuclei by fluorescence in situ hybridization. SETTINGS:
      Hospital-based laboratory for reproductive biology. PATIENT(S): A patient with
      Klinefelter's syndrome and a 46,XY fertile man were analyzed. INTERVENTION(S):
      The sperm samples were prepared for fluorescence in situ hybridization. MAIN
      OUTCOME MEASURE(S): The disomy frequencies for chromosomes 7, 9, 13, 18, and 21
      and sex chromosomes were determined using fluorescence in situ hybridization.
      RESULT(S): Significant differences were found in the frequency of disomy for
      chromosomes 13, 18, and 21 between the patient and a normospermic control. No
      significant differences were observed for chromosomes 7 and 9. The frequencies of
      gonosomal abnormalities and diploid spermatozoa were also significantly increased
      in the patient. CONCLUSION(S): Our results indicate that there is an increased
      incidence of autosomal aneuploidies for chromosomes 13, 18, and 21 in the
      spermatozoa from the patient with Klinefelter's syndrome than in the general
      population. Furthermore, most of the studies have also shown an increased
      frequency of autosomal aneuploidy in the spermatozoa from 46,XY males with
      oligozoospermia or oligoasthenoteratozoospermia. Thus, the offspring of the
      patients with Klinefelter's born by intracytoplasmic sperm injection may be at
      higher risk of autosomal aneuploidy due to oligoasthenoteratozoospermia.

PMID- 12801573
TI  - A novel sequence variation in the transactivation regulating domain of the
      androgen receptor in two infertile Finnish men.
AB  - OBJECTIVE: To study a new sequence variant at the beginning of the CAG repeat in
      the exon 1 of the androgen receptor gene. DESIGN: Controlled clinical study.
      SETTINGS: Healthy volunteers in an academic research environment. PATIENT(S):
      Sixty-two Finnish men with spermatogenic failure and 60 controls.
      INTERVENTION(S): ABI PRISM 377 (Applied Biosystems, Foster City, CA) automated
      sequencing. MAIN OUTCOME MEASURE(S): Determining the sequence around the CAG
      repeat of the AR gene. RESULT(S): A new 173A-->T (Q58L) substitution at the
      beginning of the CAG repeat in the transactivation-regulating domain of the
      androgen receptor was found in 2 infertile Finnish men but not in 60 other
      infertile men or 60 controls. CONCLUSION(S): As the polyglutamine tract coded by
      the CAG repeat is crucial to spermatogenesis, the 173A-->T (Q58L) substitution
      might be the cause of infertility in these two Finnish men.

PMID- 12801574
TI  - Birth after intracytoplasmic injection of epididymal sperm from a man with
      congenital bilateral absence of the vas deferens who had a robertsonian
      translocation.
AB  - OBJECTIVE: To present the first case of an infertile male with azoospermia
      related to a congenital bilateral absence of the vas deferens (CBAVD), in which
      mutations within the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene coexist with a robertsonian translocation. DESIGN: Case report. SETTINGS: A
      university hospital. PATIENT(S): A 34-year-old male with a 2-year history of
      primary infertility. INTERVENTION(S): Lymphocytic karyotype, polymerase chain
      reaction (PCR) and allele oligonucleotide-specific hybridization (ASO),
      microsurgical epididymal sperm aspiration (MESA), and intracytoplasmic sperm
      injection (ICSI). MAIN OUTCOME MEASURE(S): Physical examination and semen
      analysis. RESULT(S): Semen analyses revealed azoospermia and a well-recognized
      obstructive phenotype. Analysis of the CFTR gene revealed a compound
      heterozygosity for a 2184 del A + 2183 A --> G mutation on one allele and the 5T
      variant within the polypyrimidine tract of intron 8 on the other allele.
      Cytogenetic analyses revealed a t(13;14)(q10;q10) robertsonian translocation in
      the same patient. Microsurgical epididymal sperm aspiration allowed retrieval of
      a million mature motile spermatozoa, excluding any spermatogenic impairment
      secondary to the genetic abnormalities found in this patient. Epididymal sperm
      was used for an intracytoplasmic sperm injection program, and a normal child was
      born at term. CONCLUSION(S): This case illustrates that two distinct genetic
      defects may coexist, with a variable effect on male fertility but with important
      implications for genetic counseling of the future pregnancy.

PMID- 12801575
TI  - Partial DAZ deletions in a family with five infertile brothers.
AB  - OBJECTIVE: To study the genetic cause of infertility in a family with five
      infertile brothers. DESIGN: Case report. SETTINGS: Center for reproductive
      medicine at a university medical center. PATIENT(S): Five brothers presenting
      with primary infertility due to severely impaired spermatogenesis; also, their
      parents and two other paternally related family members. INTERVENTION(S):
      Fluorescence in situ hybridization and sequence family variant analysis was
      performed in leukocyte DNA to determine the number of deleted in azoospermia
      (DAZ) genes. Linkage analysis was performed for X chromosome inheritance, and
      mitochondrial DNA (mtDNA) was screened for mutations. MAIN OUTCOME MEASURE(S):
      DAZ gene copy number, X chromosome linkage, and mtDNA sequence. RESULT(S): With
      conventional polymerase chain reaction (PCR) analysis, no deletions of the AZFc
      region were found, but with fluorescence in situ hybridization and sequence
      family variant analysis, only two DAZ genes instead of four were detected in all
      individuals tested. The five brothers did not share an identical X chromosomal
      locus, and no mutations were found in the mtDNA of the index patient.
      CONCLUSION(S): A reduced copy number of the DAZ genes is found in five infertile
      brothers with severely impaired spermatogenesis, as well as in their normospermic
      father and in two other fertile paternally related family members. This
      illustrates that the phenotype associated with a reduced copy number of the DAZ
      genes can be extremely variable.

PMID- 12801576
TI  - Successful pregnancy and delivery after calcium ionophore oocyte activation in a
      normozoospermic patient with previous repeated failed fertilization after
      intracytoplasmic sperm injection.
AB  - To describe a successful pregnancy and delivery after calcium ionophore oocyte
      activation in a normozoospermic patient with previous repeated failed
      fertilization after intracytoplasmic sperm injection (ICSI).Case report. In vitro
      fertilization unit in a university affiliated medical center.A couple with 5
      years of unexplained primary infertility who had repeated failed fertilization
      after ICSI. Controlled ovarian hyperstimulation, oocyte pick-up, ICSI, assisted
      oocyte activation with calcium ionophore, embryo culture, and ET. Fertilization
      rate, implantation, pregnancy, and delivery. Assisted oocyte activation with
      calcium ionophore A23187 after ICSI resulted in reasonable fertilization rates in
      three cycles (4/6, 5/16 and 7/20 oocytes). Two pregnancies were achieved; the
      first ended with second trimester miscarriage due to fetal anomaly and the second
      with a delivery of three healthy babies.Calcium ionophore oocyte activation seems
      to be a useful method in cases of repeated failed fertilization after ICSI.

PMID- 12801577
TI  - Successful treatment of anabolic steroid-induced azoospermia with human chorionic
      gonadotropin and human menopausal gonadotropin.
AB  - OBJECTIVE: To document for the first time the successful treatment using human
      chorionic gonadotropin (hCG) and human menopausal gonadotropins (hMG) of anabolic
      steroid-induced azoospermia that was persistent despite 1 year of cessation from
      steroid use. DESIGN: Clinical case report. SETTINGS: Tertiary referral center for
      infertility. PATIENT(S): A married couple with primary subfertility secondary to
      azoospermia and male hypogonadotropic hypogonadism. The husband was a bodybuilder
      who admitted to have used the anabolic steroids testosterone cypionate,
      methandrostenolone, oxandrolone, testosterone propionate, oxymetholone,
      nandrolone decanoate, and methenolone enanthate. INTERVENTION(S): Twice-weekly
      injections of 10,000 IU of hCG (Profasi; Serono) and daily injections of 75 IU of
      hMG (Humegon; Organon) for 3 months. MAIN OUTCOME MEASURE(S): Semen analyses,
      pregnancy. RESULT(S): Semen analyses returned to normal after 3 months of
      treatment. The couple conceived spontaneously 7 months later. CONCLUSION(S):
      Steroid-induced azoospermia that is persistent after cessation of steroid use can
      be treated successfully with hCG and hMG.

PMID- 12801578
TI  - Sperm chromosome aneuploidy analysis in a man with globozoospermia.
AB  - OBJECTIVE: To determine the frequencies of chromosome aneuploidy and diploidy in
      sperm from a male with globozoospermia. DESIGN: Assessment of sperm chromosome
      aneuploidy and diploidy frequencies by multicolor fluorescence in situ
      hybridization (FISH) analysis. SETTINGS: University research laboratory.
      PATIENT(S): An infertile patient with round-headed sperm (globozoospermia).
      INTERVENTION(S): Sperm samples were obtained by masturbation for cytogenetic
      analysis. MAIN OUTCOME MEASURE(S): Aneuploidy and diploidy frequencies were
      assessed by multicolor FISH analysis for chromosomes 1, 15, 21, X, and Y and
      compared with those of five control donors. RESULT(S): A minimum of 10,000 sperm
      was analyzed per chromosome probe, for a total of 30,145 sperm. There was a
      statistically significantly increased frequency of XY disomy in the man with
      globozoospermia compared with the case in normal donors. The frequency of
      aneuploidy for chromosomes 1, 15, 21, XX, and YY was not statistically
      significantly increased. The frequency of diploidy was also not statistically
      significantly different. CONCLUSION(S): A previous report demonstrated an
      increased frequency of chromosome 15 aneuploidy in sperm of a globozoospermia
      patient who fathered a trisomy 15 conceptus. No other report has studied the
      frequency of chromosome 15 aneuploidy in these infertile men. Our study does not
      demonstrate an increased risk for chromosome 15 aneuploidy associated with
      globozoospermia. However, an elevated frequency of XY disomy was discovered,
      which is the most common type of chromosome abnormality observed in sperm of
      infertile men.

PMID- 12801579
TI  - Seminal infection with Ralstonia picketti and cytolysosomal spermophagy in a
      previously fertile man.
AB  - OBJECTIVE: To determine the origin of large plaque-like cellular and acellular
      masses of debris found in the semen of a patient with otherwise normal semen
      quality and secondary infertility. DESIGN: A prospective case study. SETTINGS:
      Academic andrology laboratory. PATIENT(S): Secondary infertility patient
      presenting for routine semen evaluation. INTERVENTION(S): Following diagnosis of
      a seminal infection, the patient was treated with an antibiotic. MAIN OUTCOME
      MEASURE(S): Semen quality parameters, semen culture, and electron microscopy
      identification of cytolysosomal spermophagy. RESULT(S): Semen culture identified
      a rare infection with Ralstonia picketti and electron microscopy showed massive
      neutrophil and cytolysosomal spermophagy. Both were eliminated after antibiotic
      therapy. CONCLUSION(S): This case study documents a rare infection of the
      reproductive tract with Ralstonia picketti. Analysis of large seminal masses
      determined their origin to be primarily from acellular cytolysosomes. The
      presence of such masses in semen should be further evaluated, including semen
      culture.

PMID- 12801580
TI  - Relationship between seminal plasma-soluble transferrin receptor and
      spermatogenesis in azoospermic patients.

PMID- 12801581
TI  - Effects of 24-hour incubation after freeze-thawing on DNA fragmentation of
      testicular sperm from infertile and fertile men.

PMID- 12801582
TI  - Immotilin, a novel sperm immobilizing protein.

PMID- 12801583
TI  - Biochemical and molecular studies of the proacrosin/acrosin system in patients
      with unexplained infertility.

PMID- 12801584
TI  - Low levels of serum inhibin B do not exclude successful sperm recovery in men
      with nonmosaic Klinefelter syndrome.

PMID- 12801585
TI  - Stimulants and other drugs of abuse and their effects on neuropeptides and the
      peptidergic systems. Proceedings of a symposium. Marco Island, Florida, USA. June
      28-29, 2002.

PMID- 12801586
TI  - What we know and what we need to know about the role of endogenous CCK in
      psychostimulant sensitization.
AB  - The unique distribution of CCK and its receptors and its co-localization with
      dopamine makes it ideally situated to pay a role in dopamine-mediated reward and
      psychostimulant sensitization. A number of studies support the hypothesis that
      CCK acting through the CCK 1 and CCK 2 receptors is an endogenous modulator of
      dopamine neurotransmission. Behavioral studies with CCK antagonists and CCK 1
      receptor mutant rats support a role for endogenous CCK in behavioral
      sensitization to psychostimulants. CCK microdialysis studies in the nucleus
      accumbens (NAC) have demonstrated that extracellular CCK is increased in the NAC
      by psychostimulants, providing neurochemical evidence that CCK could be involved
      in the behavioral response to psychostimulants. A model for how CCK may be acting
      in multiple brain regions to foster sensitization is presented and the gaps in
      our knowledge about the role of CCK in psychostimulant sensitization are
      described.

PMID- 12801587
TI  - Neuropeptide-processing carboxypeptidases.
AB  - Neuropeptides are generally produced from precursor proteins by selective
      cleavage at specific sites, usually involving basic amino acids. Enzymes such as
      the prohormone convertases and carboxypeptidase E are highly specific for these
      basic amino acid-containing sites. In addition to this "traditional" pathway,
      several neuropeptides are known to be cleaved at non-basic sites, and the enzymes
      responsible for these cleavages have not been conclusively identified. In a
      recent search for novel members of the metallocarboxypeptidase family, we found
      three human genes. One of these, named "CPA-5," has a specificity for C-terminal
      hydrophobic amino acids and mRNA expression in brain, pituitary, and testis. To
      test whether CPA-5 protein has a distribution pattern in pituitary that is
      consistent with a role for this enzyme in the non-basic processing of
      proopiomelanocortin-derived peptides such as beta-endorphin and
      adrenocorticotropin, we examined the distribution of CPA-5 using
      immunocytochemistry. In the pituitary, CPA-5 is detected in the neurointermediate
      lobe and in scattered cells in the anterior lobe. In the AtT-20 corticotroph cell
      line, CPA-5 has a perinuclear distribution. Taken together, these results are
      consistent with a role for CPA-5 in the intracellular processing of
      proopiomelanocortin-derived peptides at non-basic sites.

PMID- 12801589
TI  - Neurotensin agonists: possible drugs for treatment of psychostimulant abuse.
AB  - Although many neuropeptides have been implicated in the pathophysiology of
      psychostimulant abuse, the tridecapeptide neurotensin holds a prominent position
      in this field due to the compelling literature on this peptide and
      psychostimulants. These data strongly support the hypothesis that a neurotensin
      agonist will be clinically useful to treat the abuse of psychostimulants,
      including nicotine. This paper reviews the evidence for a role for neurotensin in
      stimulant abuse and for a neurotensin agonist for its treatment.

PMID- 12801588
TI  - Peptide and nonpeptide ligands for the nociceptin/orphanin FQ receptor ORL1:
      research tools and potential therapeutic agents.
AB  - The 17-amino acid neuropeptide nociceptin/Orphanin FQ (N/OFQ) was recently
      identified as the endogenous ligand for the opioid receptor-like (ORL1) receptor,
      a fourth member of the classical mu, delta, and kappa opioid receptor family.
      Although ORL1 clearly belongs to the opioid receptor family, it does not bind
      classical opiates and the ORL1-N/OFQ system has pharmacological actions distinct
      from the opioid receptor system. This new ligand-receptor system has generated
      active interest in the opioid community because of its wide distribution and
      involvement in a myriad of neurological pathways. The past two years have
      witnessed tremendous advances in the design and discovery of very potent and
      selective peptide and nonpeptide agonist and antagonist ligands at ORL1. These
      discoveries have facilitated the understanding of the role of the ORL1-N/OFQ
      system in a variety of processes such as pain modulation, anxiety, food intake,
      learning, memory, neurotransmitter release, reward pathways, and tolerance
      development. The ORL1 receptor therefore represents a new molecular target for
      the design of novel agents for anxiety, analgesia, and drug addiction. Indeed,
      there is tremendous interest in the pharmaceutical industry in the development of
      nonpeptide ligands such as the potent ORL1 agonist, Ro 64-6198, as anxiolytics
      and the ORL1 antagonist JTC-801 as novel analgesics. This review presents an
      overview of the various peptide and nonpeptide ORL1 ligands with an emphasis on
      their potential therapeutic utility in various human disorders.

PMID- 12801590
TI  - Conversion of delta-, kappa- and mu-receptor selective opioid peptide agonists
      into delta-, kappa- and mu-selective antagonists.
AB  - 2',6'-Dimethyl substitution of the Tyr(1) residue of opioid agonist peptides and
      deletion of the positively charged N-terminal amino group or its replacement with
      a methyl group has recently been shown to represent a general structural
      modification to convert opioid peptide agonists into antagonists. This conversion
      requires the syntheses of opioid peptide analogues containing either 3-(2,6
      dimethyl-4-hydroxyphenyl)propanoic acid (Dhp) or (2S)-2-methyl-3-(2,6-dimethyl-4
      hydroxyphenyl)propanoic acid [(2S)-Mdp] in place of Tyr(1). Using this approach,
      delta-, kappa- and mu-selective opioid peptide agonist peptides were successfully
      converted into corresponding delta-, kappa- and mu-selective antagonists, whereby
      receptor selectivity was often maintained or even improved. Thus, two (2S)-Mdp(1)
      analogues of the delta-selective cyclic enkephalin analogue H-Tyr-c[D-Pen-Gly
      Phe(pF)-Pen]-Phe-OH turned out to be potent and selective delta antagonists. Most
      successful was the development of kappa antagonists derived from dynorphin A (Dyn
      A), including the highly potent and selective kappa-antagonist [(2S)-Mdp(1)]Dyn
      A(1-11)-NH(2) (dynantin) and the enzymatically stable octapeptide analogue [(2S)
      Mdp(1),MeArg(7),D-Leu(8)]Dyn A(1-8)-NH(2). The (2S)-Mdp(1)-analogues of dynorphin
      B and alpha-neoendorphin also were kappa antagonists and may be useful as
      pharmacological tools in studies of kappa receptor subtypes. Finally, the Dhp(1)
      analogues of the mu-selective cyclic enkephalin analogue H-Tyr-c[N(epsilon
      ),N(beta)-carbonyl-D-Lys(2),Dap(5)]enkephalinamide and of endomorphin-2 were
      moderately potent mu opioid antagonists.

PMID- 12801591
TI  - Design of novel peptide ligands which have opioid agonist activity and CCK
      antagonist activity for the treatment of pain.
AB  - Disease states such as neuropathic pain offer special challenges in drug design
      due to the system changes which accompany these diseases. In this manuscript we
      provide an example of a new approach to drug design in which we have modified a
      potent and selective peptide ligand for the CCK-2 receptor to a peptide which has
      potent agonist binding affinity and bioactivity at delta and mu opioid receptors,
      and simultaneous antagonist activity at CCK receptors. De novo design based on
      the concept of overlapping pharmacophores was a central hypothesis of this
      design, and led to compounds such as H-Tyr-DPhe-Gly-DTrp-NMeNle-Asp-Phe-NH(2)
      (i.e., RSA 601) which have the designed properties.

PMID- 12801592
TI  - Determination of ligand-receptor interactions of cholecystokinin by nuclear
      magnetic resonance.
AB  - To date high resolution structural studies of G protein coupled receptors, with
      the exception of rhodopsin, have not been feasible using conventional
      spectroscopic techniques. To overcome these difficulties, the structural features
      of partial or intact domains of GPCRs have been studied by nuclear magnetic
      resonance spectroscopy and X-ray crystallography. Here, we describe the
      structural characterization of receptor domains from the cholecystokinin 1 and 2
      receptors and the elucidation of intermolecular interactions between the
      extracellular receptor domains and CCK-8 by solution state nmr.

PMID- 12801593
TI  - Interactions of norepinephrine and galanin in the central amygdala and lateral
      bed nucleus of the stria terminalis modulate the behavioral response to acute
      stress.
AB  - Many aspects of drug abuse and addiction share neurobiological substrates with
      the modulatory processes underlying the response and adaptation to acute stress.
      In particular, the ascending noradrenergic system has been implicated in
      facilitating the response to stress, and in stress-induced reinstatement of drug
      seeking behavior. Thus, to better understand the link between stress and
      addictive behaviors, it would be informative to understand better the modulatory
      function of the ascending noradrenergic system, and its interaction with other
      neurotransmitters with which it is closely associated or co-localized, such as
      the neuropeptide galanin. In this paper, we review a series of studies
      investigating the functional interactions of norepinephrine and galanin in
      modulating the behavioral response to acute stress in two components of the
      extended amygdala, the central nucleus of the amygdala and the lateral bed
      nucleus of the stria terminalis. We showed that norepinephrine facilitates
      behavioral reactivity to stress on the elevated plus-maze and social interaction
      tests. However, when stress-induced activation of the noradrenergic system was
      enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was
      recruited in the central amygdala, acting to attenuate the behavioral response to
      stress. By contrast, stress-induced galanin release in the lateral bed nucleus
      appeared to be independent of enhanced noradrenergic activation, and unlike the
      central amygdala, both galanin and norepinephrine facilitated behavioral stress
      reactivity in the bed nucleus. The different modes of interaction and
      differential region- and response-specificity of galanin and norepinephrine
      suggest that a complex neural circuit interconnecting these two regions is
      involved in the modulatory effects of norepinephrine and galanin on the
      behavioral response to stress. Such complexity may allow for flexibility and
      plasticity in stress adaptation, and may also contribute to behavioral changes
      induced by chronic drug administration. Thus, the interaction of galanin and
      norepinephrine may be a viable target for the future development of novel
      therapeutic strategies for treating behavioral disorders related to stress or
      drug abuse.

PMID- 12801595
TI  - CART peptides are modulators of mesolimbic dopamine and psychostimulants.
AB  - CART peptide produces behavioral effects when injected into the VTA or nucleus
      accumbens. In the VTA, the peptide behaves like an endogenous psychostimulant and
      produces increased locomotor activity and conditioned place preference. Since
      this is blocked by dopamine receptor blockers, it presumably involves release of
      dopamine. But in the nucleus accumbens, CART peptide reduces the locomotor
      increasing effects of cocaine. This suggests that the peptide is an interesting
      target for medications development.

PMID- 12801594
TI  - Substance P and cholecystokinin regulate neurochemical responses to cocaine and
      methamphetamine in the striatum.
AB  - The mechanism of action of drugs of abuse like cocaine and amphetamines has been
      studied extensively in the dopamine terminal field areas of the caudate-putamen
      (CPu) and the nucleus accumbens (NAc) of the rodent brain. These brain regions
      contain several neuropeptides that must play important roles in the normal
      physiological functions of these brain regions. The study of neuropeptide
      physiology in the context of the neurobiological responses to drugs of abuse may
      shed some light on the intrinsic mechanism of action of neuropeptides of the CPu
      and the NAc. The neuropeptides substance P (SP) and cholecystokinin (CCK) are
      present in the striatum where they could play an important role regulating the
      effects of psychostimulants like cocaine and amphetamines (methamphetamine [METH]
      is a long acting derivative of d-amphetamine). These highly addictive agents
      induce the release of dopamine (DA) (and other catecholamines) from dopaminergic
      terminals of the striatum. The excessive release of DA in the striatum and the
      NAc has been implicated in the habit-forming properties of these drugs. In order
      to study the contribution of SP and CCK in the striatum during psychostimulant
      treatment, we employed selective non-peptide neurokinin-1 (NK-1) and
      cholecystokinin-2 (CCK-2) receptor antagonists that readily cross the blood brain
      barrier. We infused the neurokinin-1 receptor (NK-1R) antagonist, L-733,060, into
      the striatum of freely moving rats via a microdialysis probe in order to assess
      the effects of SP on cocaine-induced DA overflow in the striatum. Infusion of the
      NK-1R antagonist prior to a systemic injection of cocaine (10 mg/kg i.p.)
      significantly attenuated DA overflow in the striatum. Conversely, infusion of a
      CCK-2 receptor (CCK-2R) antagonist, L-369,293, through the microdialysis probe
      evoked DA overflow in the striatum in the absence of cocaine and potentiated DA
      overflow after a single injection of cocaine (10 mg/kg i.p.). Exposure to METH
      (10 mg/kg 4x at two-hour intervals) produced deficits of dopamine transporters
      (DAT) in mice striatum that are detectable three days after the treatment and are
      long lasting. Pre-treatment (i.p. injections) with the NK-1R antagonist, WIN
      51,708 30 minutes before the 1st and 4th injections of METH prevented the loss of
      DAT in the striatum. Moreover, pre-treatment with the NK-1R antagonist prevents
      METH-induced cell death. Taken together, these results demonstrate that the NK-1R
      and the CCK-2R are important modulators of the actions of the psychostimulants
      cocaine and METH. Neuropeptide receptors represent an important control point
      mediating the effects of the neurotransmitter DA in the striatum of the rodent
      brain.

PMID- 12801596
TI  - Dynorphin and the hypothalamo-pituitary-adrenal axis during fetal development.
AB  - Although dynorphin has long been considered an endogenous opioid peptide with
      high affinity for the kappa-opioid receptor, its biological function remains
      uncertain. The high concentration of dynorphin peptides and kappa-opioid
      receptors in the hypothalamus suggest a possible role for dynorphin in
      neuroendocrine regulation. This review will summarize evidence that support a
      role for dynorphin in regulation of the developing hypothalamo-pituitary-adrenal
      (HPA) axis. Dynorphin can exert dual actions on adrenocorticotropin (ACTH)
      release: (i) via activation of hypothalamic kappa-opioid receptors leading to
      release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP),
      and (ii) via a non-opioid mechanism that involves N-methyl-D-aspartate (NMDA)
      receptors and prostaglandins, and which is not dependent on CRH or AVP. The
      primary site of action of dynorphin and NMDA appears to be the fetal hypothalamus
      or a supra-hypothalamic site. The non-opioid mechanism does not mature until a
      few days prior to parturition and is active for only the brief perinatal period.
      In contrast, the opioid mechanism behaves as a constitutive system with sustained
      activity from prenatal to postnatal life. It is likely that the two mechanisms
      may respond to different stress stimuli and play a different role during
      development.

PMID- 12801597
TI  - Lateral hypothalamic neuropeptides in reward and drug addiction.
AB  - The hypothalamus has been long considered important in feeding and other
      motivated behaviors. The identification of neuropeptides expressed in the
      hypothalamus has initiated efforts to better elucidate the underlying molecular
      mechanisms involved. The neuropeptides orexin and melanin-concentrating hormone
      (MCH) are expressed in the lateral hypothalamus (LH) and have been implicated in
      regulation of feeding behavior. Neurons expressing these neuropeptides have
      extensive projections to regions of the brain important for behavioral responses
      to drugs of abuse, raising the possibility that the pathways may also be
      important in addiction. Regulation of LH intracellular signaling pathways in
      response to drugs of abuse supports a role for the LH neuropeptides in addiction.

PMID- 12801598
TI  - In vitro regulation of corticotropin-releasing hormone.
AB  - Studies involving regulation of corticotropin-releasing hormone (CRH) in vitro
      have been used to validate findings obtained in vivo and more importantly have
      been used as model systems to better understand signalling mechanisms responsible
      for the expression of the CRH gene and peptide. Many in vitro studies examining
      CRH have utilized hypothalamic tissue while a few have focused on the amygdala.
      Clonal cell lines have also been utilized as models of central nervous system CRH
      neurons. Stimuli that have been implicated in regulating hypothalamic CRH
      regulation in vitro include protein kinase A (PKA) and protein kinase C (PKC)
      activators, glucocorticoids, biogenic amines, cytokines and the gaseous
      neurotransmitters. Amygdalar CRH levels in vitro are affected by some of the same
      stimuli that regulate hypothalamic CRH; however there is evidence supporting
      differential regulation of CRH in these two brain regions by some of the same
      stimuli. Only a few studies in aggregate have investigated signal transduction
      mechanisms and these studies have focused on PKA- and glucocorticoid-mediated
      changes in CRH expression. Thus, much more investigative work in better
      understanding CRH regulation in vitro is needed.

PMID- 12801599
TI  - Induction of pain facilitation by sustained opioid exposure: relationship to
      opioid antinociceptive tolerance.
AB  - Opioid analgesics are frequently used for the long-term management of chronic
      pain states, including cancer pain. The prolonged use of opioids is associated
      with a requirement for increasing doses to manage pain at a consistent level,
      reflecting the phenomenon of analgesic tolerance. It is now becoming clearer that
      patients receiving long-term opioid therapy can develop unexpected abnormal pain.
      Such paradoxical opioid-induced pain, as well as tolerance to the antinociceptive
      actions of opioids, has been reliably measured in animals during the period of
      continuous opioid delivery. Several recent studies have demonstrated that such
      pain may be secondary to neuroplastic changes that result, in part, from an
      activation of descending pain facilitation mechanisms arising from the rostral
      ventromedial medulla (RVM). One mechanism which may mediate such pain
      facilitation is through the increased activity of CCK in the RVM. Secondary
      consequences from descending facilitation may be produced. For example, opioid
      induced upregulation of spinal dynorphin levels seem to depend on intact
      descending pathways from the RVM reflecting spinal neuroplasticity secondary to
      changes at supraspinal levels. Increased expression of spinal dynorphin reflects
      a trophic action of sustained opioid exposure which promotes an increased pain
      state. Spinal dynorphin may promote pain, in part, by enhancing the evoked
      release of excitatory transmitters from primary afferents. In this regard,
      opioids also produce trophic actions by increasing CGRP expression in the dorsal
      root ganglia. Increased pain elicited by opioids is a critical factor in the
      behavioral manifestation of opioid tolerance as manipulations which block
      abnormal pain also block antinociceptive tolerance. Manipulations that have
      blocked enhanced pain and antinociceptive tolerance include reversible and
      permanent ablation of descending facilitation from the RVM. Thus, opioids elicit
      systems-level adaptations resulting in pain due to descending facilitation,
      upregulation of spinal dynorphin and enhanced release of excitatory transmitters
      from primary afferents. Adaptive changes produced by sustained opioid exposure
      including trophic effects to enhance pain transmitters suggest the need for
      careful evaluation of the consequences of long-term opioid administration to
      patients.

PMID- 12801600
TI  - Neurotensin: dual roles in psychostimulant and antipsychotic drug responses.
AB  - Central administration of neurotensin (NT) results in a variety of
      neurobehavioral effects which, depending upon the administration site, resemble
      the effects of antipsychotic drugs (APDs) and psychostimulants. All clinically
      effective APDs exhibit significant affinities for dopamine D(2) receptors,
      supporting the hypothesis that an increase in dopaminergic tone contributes to
      schizophrenic symptoms. Psychostimulants increase extracellular dopamine (DA)
      levels and chronics administration can produce psychotic symptoms over time. APDs
      and psychostimulants induce Fos and NT expression in distinct striatal
      subregions, suggesting that changes in gene expression underlie some of their
      effects. To gain insight into the functions of NT, we analyzed APD and
      psychostimulant induction of Fos in NT knockout mice and rats pretreated with the
      NT antagonist SR 48692. In both NT knockout mice and rats pretreated with SR
      48692, haloperidol-induced Fos expression was markedly attenuated in the
      dorsolateral striatum; amphetamine-induced Fos expression was reduced in the
      medial striatum. These results indicate that NT is required for the activation of
      specific subpopulations of striatal neurons in distinct striatal subregions in
      response to both APDs and psychostimulants. This review integrates these new
      findings with previous evidence implicating NT in both APD and psychostimulant
      responses.

PMID- 12801601
TI  - Orphanin FQ/nociceptin: from neural circuitry to behavior.
AB  - Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the "orphan" opioid
      receptor ORL-1 (NOP(1)) was first identified in 1995. In the years since its
      discovery, a large body of evidence has accumulated showing that OFQ/N and its
      receptor are widely distributed in the nervous system, and showing that OFQ/N has
      potent and indiscriminate inhibitory actions on neurons in many regions. However,
      numerous studies investigating the functional role of OFQ/N in physiology or
      behavior have failed to provide a coherent view. Pain and analgesia have been the
      best studied, and administration of OFQ/N is reported to have no effect, to
      produce hyperalgesia, analgesia or anti-hyperalgesia. Effects of OFQ/N receptor
      antagonists have proved similarly contentious. In an attempt to resolve this
      controversy, we investigated the actions of OFQ/N on the activity of
      physiologically characterized neurons in the rostral ventromedial medulla, a
      region with a well-documented role in pain modulation(Heinricher et al., 1997).
      The results of those experiments demonstrate that this peptide is neither "anti
      opioid" or "anti-hyperalgesic". It is simply inhibitory. For this reason, the
      effects seen in functional studies will only be fully understood when examined in
      the context of identified neural circuits.

PMID- 12801602
TI  - High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions.
AB  - The concentration of high density lipoprotein-cholesterol (HDL-C) has been found
      consistently to be a powerful negative predictor of premature coronary heart
      disease (CHD) in human prospective population studies. There is also
      circumstantial evidence from human intervention studies and direct evidence from
      animal intervention studies that HDLs protect against the development of
      atherosclerosis. HDLs have several documented functions, although the precise
      mechanism by which they prevent atherosclerosis remains uncertain. Nor is it
      known whether the cardioprotective properties of HDL are specific to one or more
      of the many HDL subpopulations that comprise the HDL fraction in human plasma.
      Several lifestyle and pharmacological interventions have the capacity to raise
      the level of HDL-C, although it is not known whether all are equally protective.
      Indeed, despite the large body of information identifying HDLs as potential
      therapeutic targets for the prevention of atherosclerosis, there remain many
      unanswered questions that must be addressed as a matter of urgency before
      embarking wholesale on HDL-C-raising therapies as strategies to prevent CHD. This
      review summarises what is known and highlights what we still need to know.

PMID- 12801603
TI  - Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E
      deficient mice.
AB  - Hyperglycemia derived advanced glycation endproducts (AGE) have been implicated
      in diabetic atherosclerosis (AS) but the role of exogenous (dietary) AGE in the
      development of this serious complication is not known. This study evaluates the
      influence of diet-related AGE on AS in genetically hypercholesterolemic
      apolipoprotein E-deficient (apoE(-/-)), streptozotocin-induced diabetic mice.
      Diabetic and non-diabetic apoE(-/-) mice (6-8 weeks old) were randomized into
      either a standard AIN-93G chow (AGE 12,500+/-700 U/mg, termed high-AGE diet, H
      AGE), or the same chow having four to fivefold lower AGE level (L-AGE: 2,700+/
      830 U/mg) based on ELISA. After 2 months of diabetes, compared to the diabetic
      mice fed standard (H-AGE) diet, the AS lesions at the aortic root of the L-AGE
      group were >50% smaller (0.17+/-0.03 vs. 0.31+/-0.05 mm(2), P<0.05). Serum AGE
      were lower in the diabetic L-AGE than in the H-AGE mice (by approximately 53%)
      (P<0.00001), as were in the non-diabetic L-AGE vs. H-AGE groups (P<0.05). No diet
      related changes were noted in plasma glucose, triglycerides, or plasma
      cholesterol. Immunohistochemical comparisons showed markedly suppressed tissue
      AGE, AGE-Receptor-1, -2 and RAGE expression, reduced numbers of inflammatory
      cells, tissue factor, vascular cell adhesion molecule-1 and MCP-1 in the L-AGE
      diabetic group. The findings are supportive of an important link between dietary
      intake of pre-formed glycoxidation products, tissue-incorporated AGE, and
      diabetes-accelerated AS. The marked anti-atherogenic effects of an AGE-restricted
      diet in this model may provide the basis for relevant clinical studies.

PMID- 12801604
TI  - Hypercholesterolemia in pregnant mice does not affect atherosclerosis in adult
      offspring.
AB  - In humans, maternal hypercholesterolemia during pregnancy promotes microscopical
      fatty streaks in the children. The mechanism is unknown. Fatty streaks are
      clinically silent, and many of them regress and never develop into advanced
      atherosclerosis. The aim of this study was to investigate whether
      hypercholesterolemia in pregnant mice induced more advanced atherosclerosis in
      their adult progeny. Hypercholesterolemic (HC) apolipoprotein E knockout (apoE(-/
      )) female mice were mated with normocholesterolemic (NC) wild-type (apoE(+/+))
      males and vice versa. All parents were almost identical genetically except for
      apoE. Therefore, all progeny became genetically identical and heterozygous
      apoE(+/-). They were born of either HC (i.e. apoE(-/-)) or NC (i.e. apoE(+/+))
      mothers. The progeny were killed 6 months after birth and the amount of
      atherosclerosis in the aortic root was assessed. Females developed more
      atherosclerosis than males (P<0.001) but, regardless of sex, maternal
      hypercholesterolemia during pregnancy had no influence on the amount of
      atherosclerosis in adult progeny. Males of HC mothers had lower plasma
      cholesterol levels than males of NC mothers. Thus, in mice, maternal
      hypercholesterolemia during pregnancy does not promote the development of
      advanced atherosclerosis in their adult progeny.

PMID- 12801605
TI  - Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in
      dyslipidemic mice.
AB  - We have shown that the dual domain peptide Ac-hE18A-NH(2), in which LRKLRKRLLR,
      (141-150 region of human apo E) covalently linked to a class A lipid-associating
      domain, is able to associate with apo B-containing lipoproteins and enhance their
      clearance both in vitro and in vivo. We present here the differential effects of
      this peptide on the plasma cholesterol levels in different mouse models. The
      peptide intravenously administered (100 microg) into C57BL/6J mice on atherogenic
      diet, apo E null, and apo E null/LDL-receptor (LDL-R) null double knock out mouse
      models, was able to rapidly reduce plasma cholesterol levels within 2 min, and
      the effect persisted for more than 6 h. The reduction was limited to the VLDL and
      IDL/LDL fractions; HDL was not reduced in any mouse model studied. However, the
      peptide had no effect on the plasma cholesterol levels in C57BL/6J mice on normal
      diet, LDL-R null mice on normal chow, and LDL-R null mice on Western diet.
      Administration to LDL-R null mice of 125I-labelled human lipoproteins incubated
      with peptide resulted in accelerated human VLDL and LDL clearance with associated
      increase of radioactivity in the liver. These results, coupled with our earlier
      in vitro observations, indicate that the Arg-rich peptide-assisted rapid
      clearance of plasma cholesterol in dyslipidemic mice is due to the peptide
      targeting apo B-48-containing atherogenic lipoproteins to the liver for increased
      uptake and degradation.

PMID- 12801606
TI  - Inhibition of oxidized LDL aggregation with the calcium channel blocker
      amlodipine: role of electrostatic interactions.
AB  - Atherogenic low-density lipoproteins (LDL) are characterized by elevations in
      cholesterol content and increased electronegativity, factors that contribute to
      aggregation and foam cell formation. This study was designed to test the effect
      of the positively charged calcium channel blocker (CCB) amlodipine on the
      aggregation properties of oxidized LDL lipids. Large unilamellar vesicles (LUVs)
      (100 nm diameter) labeled with a non-exchangeable marker [3H]cholesteryl
      hexadecyl ether were prepared with lipids extracted from human LDL following
      oxidation. The LUVs were shown to bind, in a reversible fashion, to charged
      diethylaminoethyl Sephadex columns. The addition of amlodipine inhibited binding
      of the oxidized LDL lipids in a dose-dependent fashion with an IC(50) in the
      nanomolar range as a result of its high lipophilicity and positively charged
      amino group (pK(a) of 9.02). The activity of amlodipine was reproduced in model
      membranes that contained fixed amounts of charged phospholipid
      (glycerophospholipid) in a concentration-dependent manner. By contrast, drugs
      lacking a formal positive charge, including CCBs (felodipine, nifedipine,
      diltiazem, verapamil) and an angiotensin-converting enzyme-inhibitor
      (ramiprilate) had no effect on the column binding of the modified,
      electronegative lipids. These effects of amlodipine on LDL lipid aggregation and
      electrostatic properties may represent a novel antiatherosclerotic mechanism of
      action.

PMID- 12801607
TI  - Inhibition of Akt phosphorylation by thrombin, histamine and
      lysophosphatidylcholine in endothelial cells. Differential role of protein kinase
      C.
AB  - The protein kinase Akt is involved in embryonic vascular development and
      neoangiogenesis as well as in several endothelial cell functions, including
      activation of endothelial NO-synthase (eNOS) and promotion of endothelial cell
      survival. We have examined the effects of G-protein activators thrombin and
      histamine as well as lysophosphatidylcholine (LPC) on Akt phosphorylation in
      cultured human umbilical vein endothelial cells (HUVEC). Akt phosphorylation was
      analyzed with the phosphospecific Akt (Ser473) antibody by Western blotting.
      While epidermal growth factor (EGF) was a potent stimulator of Akt
      phosphorylation histamine, thrombin and LPC blocked its activation when used in
      cotreatment with EGF. Following inhibition or downregulation of protein kinase C
      (PKC), the inhibitory effect of both histamine and thrombin on the endothelial
      response to EGF was prevented. Furthermore, stimulation of PKC, using short-term
      12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, markedly inhibited the
      stimulatory effects of EGF on Akt phosphorylation. Rottlerin, an inhibitor of the
      PKCdelta, but not Go6976, which is an inhibitor of alpha, beta, gamma and
      isoforms, reversed the inhibitory effects of histamine. Conversely, inhibition or
      downregulation of PKC did not prevent the inhibitory effect of LPC. Akt
      phosphorylation was also increased by sphingosine 1-phosphate (S1P) treatment and
      this activity was influenced by the various cotreatments in the same way as the
      activation by EGF. Overall, this study demonstrated that the G-protein activators
      thrombin and histamine inhibited both EGF- and S1P-mediated Akt phosphorylation
      in HUVEC by activation of PKCdelta, while the inhibitory effects of LPC were
      independent of PKCdelta.

PMID- 12801608
TI  - Effects of vitamin supplementation and hyperhomocysteinemia on atherosclerosis in
      apoE-deficient mice.
AB  - It has been demonstrated that hyperhomocysteinemia (HHcy) accelerates
      atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. In this study,
      vitamin-defined chow diets were used to induce HHcy in apoE(-/-) mice in an
      attempt to identify possible pathogenic pathways. Six-week-old female apoE(-/-)
      mice were divided into seven groups: vitamin-defined purified chow diet alone
      (control), or same diet supplemented with either D,L-homocysteine (upward arrow
      Hcy) or L-homocystine (upward arrow Hcy-Hcy), or diet high in L-methionine
      (upward arrow Met), or diet high in B-vitamins (upward arrow vitamin), or diets
      deficient in folate (downward arrow folate) or vitamin B(6) ( downward arrow
      B(6)). Eighteen weeks later, plasma total homocysteine (tHcy), lipids and
      atherosclerotic plaque burden (aortic root, aortic arch, and brachiocephalic
      trunk) were measured. tHcy levels were similar in the upward arrow vitamin,
      downward arrow folate, downward arrow B(6) and control groups (9.2-10.1
      micromol/l, NS), but elevated mildly in the upward arrow Hcy-Hcy group (16.1
      micromol/l) and moderately in the upward arrow Met and upward arrow Hcy groups
      (53.6 and 51.5 micromol/l, respectively). Mice in the latter two groups had
      significantly more atherosclerosis in the aortic root. Although B vitamin
      supplementation failed to lower tHcy levels, mice had less atherosclerosis in the
      aortic arch. In summary, dietary methionine and homocysteine, but not
      homocystine, enhanced the development of atherosclerosis. Supplementation with B
      vitamins appeared to confer homocysteine-independent protection against
      atherosclerosis. These results suggest that (1) there may be a threshold level
      below which homocysteine is not atherogenic; (2) the atherogenic effect of HHcy
      may be mediated via an intracellular pathway; and/or (3) the anti-atherogenic
      effect of B vitamins in normohomocysteinemic mice is independent of tHcy levels.

PMID- 12801609
TI  - High glucose alters matrix metalloproteinase expression in two key vascular
      cells: potential impact on atherosclerosis in diabetes.
AB  - Diabetes is a major risk factor for atherosclerosis. Hyperglycemia is an
      underlying contributing factor; however, the mechanisms that mediate the vascular
      complications are not yet fully understood. In the present study, we provide
      evidence that elevated glucose induces discordant matrix metalloproteinase (MMP)
      expression from two key vascular cells, endothelial cells and macrophages. Our
      results clearly indicate that high glucose (25 mM) induced endothelial cell
      expression and activity of the collagenase, MMP-1 and the gelatinase, MMP-2,
      whilst reducing expression of the stromelysin, MMP-3 (P<0.05). Similarly, our
      results show that high glucose (25 mM) induces expression and activity of MMP-9
      from monocyte-derived macrophages (P<0.05). High glucose culture did not affect
      metalloproteinase inhibitor (TIMP-1) expression. Our results suggest for the
      first time that high glucose exposure induced discordant regulation of the
      MMP/TIMP system in vascular cells. The increased MMP-1, MMP-2 and MMP-9
      activities induced by high glucose exposure could promote matrix degradation
      thereby accelerating atherogenesis and potentially reducing plaque stability in
      diabetes.

PMID- 12801610
TI  - Degree of oxidation of low density lipoprotein affects expression of CD36 and
      PPARgamma, but not cytokine production, by human monocyte-macrophages.
AB  - Oxidized low-density lipoprotein (oxLDL) exhibits many atherogenic effects,
      including the promotion of monocyte recruitment to the arterial endothelium and
      the induction of scavenger receptor expression. However, while atherosclerosis
      involves chronic inflammation within the arterial intima, it is unclear whether
      oxLDL alone provides a direct inflammatory stimulus for monocyte-macrophages.
      Furthermore, oxLDL is not a single, well-defined entity, but has structural and
      physical properties which vary according to the degree of oxidation. We tested
      the hypothesis that the biological effects of oxLDL will vary according to its
      degree of oxidation and that some species of oxLDL will have atherogenic
      properties, while other species may be responsible for its inflammatory activity.
      The atherogenic and inflammatory properties of LDL oxidized to predetermined
      degrees (mild, moderate and extensive oxidation) were investigated in a single
      system using human monocyte-derived macrophages. Expression of CD36 mRNA was up
      regulated by mildly- and moderately-oxLDL, but not highly-oxLDL. The expression
      of the transcription factor, proliferator-activated receptor-gamma (PPARgamma),
      which has been proposed to positively regulate the expression of CD36, was
      increased to the greatest degree by highly-oxLDL. However, the DNA binding
      activity of PPARgamma was increased only by mildly- and moderately-oxLDL. None of
      the oxLDL species appeared to be pro-inflammatory towards monocytes, either
      directly or indirectly through mediators derived from lymphocytes, regardless of
      the degree of oxidation.

PMID- 12801611
TI  - Association between the Ala379Val variant of the lipoprotein associated
      phospholipase A2 and risk of myocardial infarction in the north and south of
      Europe.
AB  - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been identified as a
      coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by
      hydrolysing platelet activating factor, and pro-inflammatory generation of
      atherogenic mediators may influence CHD risk. We investigated the association of
      the activity-reducing A379V variant with risk of myocardial infarction (MI) in a
      large European case-control study, which compared 527 post-MI men with 566 age
      matched controls from north and south Europe. Overall, the frequency of the V379
      allele was 0.24 (95%CI 0.21-0.26), with no evidence for differences between
      centres. Homozygosity for the V379 allele was associated with lower risk of MI,
      (Odds Ratio (OR) 0.56, 95%CI 0.32-0.98), maintained after adjustment for
      lifestyle factors and levels of inflammatory risk factors (C-reactive protein,
      fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of
      effect between the centres in the north and south of Europe (P-value for
      interaction=0.80). Since homozygosity for V379 occurs in only 5-6% of subjects,
      this genotype is not a major determinant of population genetic risk of CHD, but
      the association of this genotype with low levels of Lp-PLA(2), strongly support
      the pro-inflammatory causative, and not consequential, role of Lp-PLA(2) in CHD.

PMID- 12801612
TI  - Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response
      to pravastatin therapy.
AB  - Statins decrease cardiovascular morbidity and mortality, essentially, by reducing
      LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol
      concentrations. Environmental and genetic factors are known to affect LDL-C
      response to statins but less is known regarding HDL-C. We have evaluated the
      lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in
      relation to the G/A polymorphism in the promoter region of the apo A-I gene in
      397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the
      study population, 61.7% were homozygous for the G allele and 36% were
      heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele
      homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis).
      However, on segregation by gender and smoking status the effect was significant
      only in non-smoking males. The A allele carriers did not increase their HDL-C
      concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele
      homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response
      between both groups were significant before (P=0.008) and after adjustment for
      confounding variables such as age and baseline HDL-C concentration (P=0.046). We
      conclude that the G/A polymorphism of the apo A-I promoter region affects not
      only baseline HDL-C concentrations but also its response to pravastatin
      treatment.

PMID- 12801613
TI  - Plasminogen activator inhibitor-1 (PAI-1) activity post myocardial infarction:
      the role of acute phase reactants, insulin-like molecules and promoter (4G/5G)
      polymorphism in the PAI-1 gene.
AB  - High PAI-1 levels post acute myocardial infarction (AMI) are associated with a
      poor outcome. Concentrations of insulin-like molecules, proinflammatory cytokines
      and an insertion (5G)/deletion (4G) polymorphism in the promoter of the PAI-1
      gene, all influence circulating PAI-1 levels. We studied the determinants of PAI
      1 in 123 patients immediately following and at 6 months after AMI. Within 24 h of
      AMI, PAI-1 levels were related to those of proinsulin-like molecules but not to
      levels of cytokines (interleukin-1beta, interleukin-6 or tumour necrosis factor
      alpha), to genotype, or to interactions between genotype and cytokine
      concentration. PAI-1 levels 6 months after AMI were related to concentrations of
      interleukin-1beta but not to genotype. We have found no evidence that subjects
      with the 4G/4G polymorphism have higher PAI-1 levels on admission or 6 months
      after AMI. In these patients, levels of PAI-1 are related to concentrations of
      proinsulin-like molecules and of proinflammatory cytokines.

PMID- 12801614
TI  - Correlations of C-reactive protein levels with anthropometric profile, percentage
      of body fat and lipids in healthy adolescents and young adults in urban North
      India.
AB  - OBJECTIVE: To investigate the relationships of sub-clinical inflammation and
      regional and generalized obesity and lipids in adolescent and young adult Asian
      Indians in north India. METHODS: We determined serum levels of C-reactive protein
      (CRP), a marker for sub-clinical inflammation, body mass index (BMI), waist
      circumference (WC), waist-to-hip ratio (W-HR), four skinfolds (biceps, triceps,
      subscapular and suprailiac), percentage of body fat (% BF) and lipid profile in
      377 healthy adolescents and young adults (331 males and 46 females, age range: 14
      25 years). RESULTS: Overweight subjects (BMI>85th percentile), and subjects with
      high values (>85th percentile) of WC and triceps skinfold thickness had
      significantly higher median CRP levels (P=0.04, P=0.001 and P=0.007,
      respectively) as compared with subjects with lower values of the variables.
      Elevated levels of CRP (>2.1 mg/l) were observed in 21.8% of the overweight
      subjects and 24.5% of the subjects with high (>85th percentile) % BF. After
      adjusting for age and gender, the odds ratios (95% CI) for elevated levels of CRP
      were 2.3 (1.1-4.7, P=0.02) for overweight subjects, 2.6 (1.2-5.4, P=0.01) for
      subjects with high % BF, and 3.7 (1.7-7.9, P=0.001) for subjects with high
      triceps skinfold thickness. Levels of CRP correlated significantly with % BF
      (r=0.13, P=0.009), W-HR (r=0.11, P=0.02), biceps skinfolds (r=0.13, P=0.01) and
      triceps skinfolds (r=0.13, P=0.01) for males only. CONCLUSIONS: The observations
      of substantial prevalence of elevated CRP levels in adolescents and young adults
      having increased generalized and abdominal adiposity may be important for the
      development of metabolic syndrome and atherosclerosis in Asian Indian adults.

PMID- 12801615
TI  - Methylenetetrahydrofolate reductase (MTHFR) 677C>T and methionine synthase
      reductase (MTRR) 66A>G polymorphisms: association with serum homocysteine and
      angiographic coronary artery disease in the era of flour products fortified with
      folic acid.
AB  - We analyzed the association between the methylenetetrahydrofolate reductase
      (MTHFR) 677C>T and methionine synthase reductase (MTRR) 66A>G polymorphisms with
      serum homocysteine and with coronary artery disease (CAD) in 504 patients
      undergoing clinically-indicated angiography between July 1998 and January 1999.
      Significant CAD (>/=50% stenosis in >/=one artery, blinded to risk factors) was
      present in 271 patients (54%). Median homocysteine (micromol/l) was 8.8
      (interquartile range: 7.5-10.7). The prevalence of the MTHFR TT, CT, and CC
      genotypes was 11, 44 and 45%, respectively. Median tHcy (with interquartile
      ranges) for the entire population was 8.8 (7.5-10.7), and for the TT, CT, and CC
      genotypes was 9.7 (8.2-11.4), 8.8 (7.5-10.7), and 8.6 (7.3-10.6) micromol/l,
      respectively (P=0.04). On multiple logistic regression analysis, the MTHFR TT
      genotype was associated with hyperhomocysteinemia (adjusted OR=3.57; 95% CI, 1.47
      8.70), but not with significant CAD. The prevalence of the MTRR AA, AG, GG
      genotypes was 19, 50 and 31%, respectively. There were no differences in mean
      homocysteine, prevalence of hyperhomocysteinemia and significant CAD between the
      three genotypes. On multivariate analysis, the MTRR genotypes were not associated
      with serum homocysteine or with significant CAD.

PMID- 12801616
TI  - Abdominal aortic hemodynamic conditions in healthy subjects aged 50-70 at rest
      and during lower limb exercise: in vivo quantification using MRI.
AB  - The prevalence of atherosclerosis in the abdominal aorta increases with age and
      is hypothesized to be related to adverse hemodynamic conditions including flow
      recirculation and low wall shear stress. Exercise has been shown to modulate
      these adverse conditions observed in the infrarenal aorta of healthy young
      subjects at rest. A custom magnetic resonance (MR)-compatible stationary cycle,
      an open MRI, and custom image processing software were used to quantify
      hemodynamic conditions in the abdominal aorta at rest and during cycling exercise
      in healthy subjects aged 50-70 years. The subjects increased their heart rate
      from 63+/-8 bpm at rest to 95+/-12 bpm during cycling exercise. Supraceliac blood
      flow increased from 2.3+/-0.4 to 6.0+/-1.4 l/min (P<0.001) and infrarenal flow
      increased from 0.9+/-0.3 to 4.9+/-1.7 l/min (P<0.001) from rest to exercise. Wall
      shear stress increased from 2.0+/-0.7 to 7.3+/-2.4 dynes/cm(2) at the supraceliac
      level (P<0.001) and 1.4+/-0.8 to 16.5+/-5.1 dynes/cm(2) at the infrarenal level
      (P<0.001) from rest to exercise. Flow and shear oscillations present at rest were
      eliminated during exercise. At rest, these older subjects experienced lower mean
      wall shear stress at the supraceliac level of the aorta and greater oscillations
      in wall shear stress as compared to a group of younger subjects (23.6+/-2.2
      years). Compared to the younger subjects, the older subjects also experienced
      greater increases in mean wall shear stress and greater decreases in wall shear
      stress oscillations from rest to exercise.

PMID- 12801617
TI  - Flow-responsive remodeling after angioplasty is enhanced by high cholesterol
      diet. Prevention with pyrrolidine dithiocarbamate.
AB  - We examined the effects of high cholesterol diet and pyrrolidine dithiocarbamate
      (PDTC) on flow-dependent remodeling after angioplasty. After right common carotid
      balloon-injury, the right external carotid (low flow) or left common carotid
      artery were ligated (high flow) in rabbits fed normal diet, 1% cholesterol diet
      without or with the antioxidant PDTC for 7 days pre- and 7-28 days post-injury.
      Angiographic lumen diameter was significantly greater at 28 days in high flow
      than low flow normal diet animals, attributable on perfusion-fixed vessel
      morphometry to altered remodeling (area within the external elastic lamina: high
      flow 1.85+/-0.24 vs. low flow 1.31+/-0.04 mm(2), P<0.05) rather than differences
      in neointima formation or vessel tone. In animals on 1% cholesterol diet high
      flow remodeling was significantly enhanced (area within the external elastic
      lamina 3.13+/-0.17 mm(2), P<0.05 vs. high flow normal diet) but low flow inward
      remodeling was similar (area within the external elastic lamina 1.29+/-0.07
      mm(2)). Mean Doppler flow velocities (initial/post-ligation/28 day follow-up,
      cm/s) had almost normalized in normal diet animals (high flow 30/49/35, low flow
      32/9/26) but showed overcompensation in 1% cholesterol diet animals (high flow
      32/49/22, low flow 30/11/25). PDTC therapy markedly attenuated remodeling (area
      within the external elastic lamina: high flow 2.20+/-0.18, and low flow 2.00+/
      0.11 both P<0.05 vs. 1% cholesterol diet alone) and flow velocities only
      partially normalized (high flow 26/42/34, low flow 27/7/16). We conclude that
      hypercholesterolemia enhances and PDTC attenuates flow-dependent remodeling after
      angioplasty.

PMID- 12801618
TI  - Cholesterol synthesis and absorption in coronary patients with lipid triad and
      isolated high LDL cholesterol in a 4S subgroup.
AB  - We assumed that assaying serum cholesterol precursors (synthesis markers) and
      plant sterols and cholestanol (absorption markers of cholesterol) reveals
      differences in cholesterol synthesis and absorption in the Finnish 4S subgroup
      divided in high triglyceride-low HDL cholesterol (lipid triad=HTG) and isolated
      high LDL cholesterol (ILDL) groups. Serum squalene and non-cholesterol sterol
      ratios to cholesterol were measured with gas-liquid chromatography at baseline, 6
      weeks, 1 year, and 5 years on simvastatin. Patients with HTG (n=135) exhibited
      features of metabolic syndrome and, in spite of similar serum total and LDL
      cholesterol levels, ratios of synthesis markers were higher and those of
      absorption markers lower than in ILDL (n=133). The latter patients accumulated to
      a subgroup shown earlier to be clinical non-responders to simvastatin in 4S.
      Serum cholesterol reduction by simvastatin only tended to be higher in HTG than
      ILDL. The synthesis marker ratios were markedly reduced, and more effectively in
      HTG than ILDL, while the absorption marker ratios were increased, and for plant
      sterols more in ILDL than HTG. In conclusion, HTG is associated with high
      synthesis and low absorption of cholesterol, these events being opposite in ILDL.
      Synthesis is more effectively reduced by simvastatin in HTG than ILDL in spite of
      similar reduction in serum cholesterol. Patients defined by highest baseline
      absorption marker ratios in ILDL group are poor coronary event-reducers on
      regular simvastatin treatment.

PMID- 12801619
TI  - The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count:
      findings from the Third National Health and Nutrition Examination Survey.
AB  - To examine the association between the metabolic syndrome and C-reactive protein,
      fibrinogen, and leukocyte count, the author did a cross-sectional analysis of
      data from 8570 participants aged >/=20 years from the Third National Health and
      Nutrition Examination Survey (1988-1994). The metabolic syndrome was defined
      using criteria established by the Third Report of the National Cholesterol
      Education Program Expert Panel on Detection, Evaluation, and Treatment of High
      Blood Cholesterol in Adults. The age-adjusted prevalence of having an elevated C
      reactive protein concentration was 29.0% (S.E.: 1.6%) for participants with the
      metabolic syndrome and 12.1% (S.E.: 0.6%) for participants without the metabolic
      syndrome (adjusted odds ratio (OR), 2.80; 95% confidence interval (CI): 2.36,
      3.33). Compared with participants who had no abnormalities, the corresponding
      adjusted ORs were 1.91 (95% CI: 1.27, 2.87), 3.00 (95% CI: 1.96, 4.60), 5.01 (95%
      CI: 3.39, 7.41), 5.97 (95% CI: 3.83, 9.31), and 6.79 (95% CI: 3.55, 12.99) for
      participants with 1, 2, 3, 4, and 5 metabolic abnormalities, respectively.
      Participants with the metabolic syndrome had higher fibrinogen concentrations and
      white blood cell counts than those without this syndrome. Many people with the
      metabolic syndrome have a low-grade inflammation, which may increase their risk
      for future adverse events. A better understanding of the potential consequences
      of the high prevalence of low-grade inflammation among people with the metabolic
      syndrome is needed.

PMID- 12801620
TI  - Atorvastatin markedly improves type III hyperlipoproteinemia in association with
      reduction of both exogenous and endogenous apolipoprotein B-containing
      lipoproteins.
AB  - Remnant lipoproteins are known to promote atherosclerosis especially in patients
      with type III hyperlipoproteinemia (HLP). In the current study, the effects of
      atorvastatin were investigated with special reference to the exogenous and
      endogenous apolipoprotein (apo) B-containing lipoprotein metabolism in type III
      HLP. Four Japanese male patients with type III HLP associated with homozygous
      apoE2 were studied. One-month administration of atorvastatin (20 mg once daily),
      after a 4-week dietary run-in, strikingly reduced serum total cholesterol and
      triglyceride (TG) levels by 52 (P<0.01) and 56% (P<0.05), respectively.
      Atorvastatin further decreased remnant-like particle (RLP)-cholesterol by 73% and
      RLP-TG by 65% (P<0.05), respectively. Distribution analysis by polyacrylamide gel
      disc electrophoresis clearly showed that atorvastatin diminished very low-,
      intermediate- and low-density lipoprotein particles. The relative particle
      diameter of intermediate-density lipoprotein became smaller after atorvastatin
      treatment (P<0.01). Furthermore, ultracentrifugal analysis demonstrated that
      atorvastatin significantly decreased cholesterol, TG and phospholipid
      concentrations in all apoB-containing lipoprotein fractions and very low-density
      lipoprotein (VLDL)-cholesterol/serum TG ratio (P<0.05), implying atorvastatin
      induced reduction of beta-VLDL. Finally, newly developed assays of apoB-48 and
      apoB-100 revealed that atorvastatin markedly reduced these apolipoproteins by 43
      and 52%, respectively (P<0.01), suggesting that atorvastatin decreased the number
      of both exogenous and endogenous apoB-containing lipoproteins. Taken together,
      atorvastatin improves remnant lipoprotein metabolism in type III HLP both in
      quality and in quantity. Atorvastatin can be one of the optimal options for the
      treatment of patients with type III HLP.

PMID- 12801621
TI  - Endothelin type A receptor antagonism restores myocardial perfusion response to
      adenosine in experimental hypercholesterolemia.
AB  - Experimental hypercholesterolemia is characterized by increased endothelin-1 (ET
      1) activity and is associated with an attenuated myocardial perfusion response
      and an inappropriate increase in coronary microvascular permeability during
      episodes of increased myocardial demand. This study was designed to determine the
      effect of chronic selective ET type A (ET(A)) receptor antagonism on coronary
      vascular response to simulated cardiac stress in experimental
      hypercholesterolemia. Twenty-one pigs were randomized to three groups: normal
      diet (N), high-cholesterol diet (HC), and HC diet plus ABT-627, a selective ET(A)
      receptor antagonist, (HC+ABT-627). After 12 weeks, cardiac electron beam computed
      tomography (EBCT) was performed before and during intravenous infusion of
      adenosine, and myocardial perfusion (ml/min per g) and coronary microvascular
      permeability index (arbitrary units) were calculated. Basal myocardial perfusion
      was similar in all groups (N: 0.91+/-0.10; HC: 0.95+/-0.08; HC+ABT-627: 1.03+/
      0.09; P=0.64). Adenosine infusion led to a significant increase in myocardial
      perfusion in the N (1.32+/-0.15; P<0.001) but not in the HC (0.95+/-0.07) group.
      However, in the HC+ABT-627 group, adenosine also significantly increased
      myocardial perfusion (1.33+/-0.12; P=0.001). Basal permeability index did not
      differ between the groups (N: 1.56+/-0.13; HC: 1.34+/-0.19; HC+ABT-627: 1.62+/
      0.10; P=0.38). Adenosine infusion significantly increased permeability index in
      HC pigs (2.29+/-0.22; P<0.001) but not in N (1.71+/-0.21) and HC+ABT-627 (1.82+/
      0.08) pigs. We conclude that chronic selective ET(A) receptor antagonism
      preserves myocardial perfusion response and coronary microvascular integrity
      during episodes of increased myocardial demand in experimental
      hypercholesterolemia, indicating an important role for the endogenous endothelin
      system in this disorder.

PMID- 12801622
TI  - Effect of xuezhikang, a cholestin extract, on reflecting postprandial
      triglyceridemia after a high-fat meal in patients with coronary heart disease.
AB  - The effect of xuezhikang on postprandial triglyceride (TG) level was investigated
      in patients with coronary heart disease (CHD) after a high-fat meal (800 cal; 50
      g fat). Fifty CHD patients were randomly divided into two groups to accept
      xuezhikang (xuezhikang group) 1200 mg/day (600 mg twice daily) or not (control
      group) on the base of routine therapy which included aspirin, metoprolol and
      fosinopril and nitrates during the whole 6 weeks following-up. Xuezhikang
      significantly reduced fasting serum total cholesterol (TC) (-20%), low-density
      lipoprotein cholesterol (LDL-C, -34%), TG (-32%) and apoB (-27%) levels, and
      raised fasting high-density lipoprotein cholesterol (HDL-C, 18%) and apoA-I (13%)
      levels (P<0.001). The postprandial serum TG levels at 2, 4 and 6 h decreased 32,
      38 and 43%, respectively, in xuezhikang group (P<0.001). The TG area under the
      curve over the fasting TG level (TG-AUC) significantly decreased in CHD patients
      accepted xuezhikang with normal (less than 1.7 mmol/l) and elevated (1.74 to 2.92
      mmol/l) fasting TG levels by 45 and 50%, respectively (P<0.001). Routine therapy
      had no significant effect on the fasting and postprandial lipid and
      apolipoprotein levels. The change of TG-AUC was significantly related to the
      changes of fasting TG, TC, LDL-C, and HDL-C levels after the treatment, which
      were related to the changes of fasting apoA-I and apoB levels significantly
      (P<0.001). Xuezhikang was shown to be beneficial in the treatment of reflecting
      postprandial triglyceridemia in CHD patients with normal and mildly elevated
      fasting TG levels.

PMID- 12801623
TI  - Characterization of polymorphic structure of SREBP-2 gene: role in
      atherosclerosis.
AB  - Sterol regulatory element binding proteins (SREBPs) are membrane-bound
      transcription factors that control the metabolism of cholesterol and fatty acids
      in mammalian cells. We postulated that polymorphisms (SNPs) in SREBP-2 gene might
      influence lipid parameters and the risk of coronary atherosclerosis. PCR-SSCP
      analysis and direct sequencing of DNA from 64 asymptomatic hypercholesterolemic
      men revealed seven genetic SREBP-2 SNPs. The genotype distribution of four of
      these SNPs (1668G>T, 1784G>C, 3474T>C and 3705C>T), and their influence on plasma
      lipid values and clinical parameters was studied in 655 asymptomatic men
      previously selected for the presence of at least one cardiovascular risk factor
      (hypertension, hypercholesterolemia, tobacco consumption). No significant
      relation was found with lipid parameters but there was a significant association
      between the 1784G>C polymorphism and intima-media thickness (IMT) measured in 497
      subjects. Thus, a common variation in the SREBP-2 gene is related with early
      stage carotid atherosclerosis in subjects with a risk of cardiovascular events
      without detectable change in plasma lipid levels.

PMID- 12801624
TI  - Haptoglobin elutes from human atherosclerotic coronary arteries--a potential
      marker of arterial pathology.
AB  - BACKGROUND: Molecules which egress from atherosclerotic arteries may function as
      plasma markers of arterial pathology, but such egress has not been proven with
      living human coronary arteries. We hypothesised that proteins eluting from the
      arterial wall may discriminate between atherosclerotic and non-atherosclerotic
      coronary arteries. METHODS AND RESULTS: During cardiac bypass surgery, 155
      sequential fractions of antegradely flushed coronary cardioplegia solution were
      collected by balloon-cuffed catheter from the coronary sinus in subjects with
      angiographically extensive (n=30) or minor (n=7) coronary disease. Although
      plasma was the major source of protein in heavily blood-contaminated samples,
      under conditions of low blood contamination (<0.5 mg/ml red cell Haemoglobin)
      coronary circulation-derived protein was detected. N-terminal sequencing of a
      major 40 kDa band detected by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) demonstrated 100% homology with beta chain of
      Haptoglobin (Hpt). Comparison of perfusates from patients with and without
      significant coronary disease found that the concentration of Hpt was markedly
      increased in perfusates from atherosclerotic coronary arteries (0.099+/-0.017
      microg Hpt/microg Hb) relative to controls (0.016+/-0.008 microg Hpt/microg Hb,
      P=0.0027). Analysis of peripheral plasma samples of the same subjects, and of a
      separate cohort of patients, confirmed greater Hpt in those with angiographic
      coronary disease than in those without disease. CONCLUSIONS: Proteins such as Hpt
      elute from the human coronary vascular bed and may differentiate between arteries
      with minor or extensive atherosclerosis. Although the suitability of Hpt as a
      circulating plasma marker for atherosclerosis remains to be established, the
      approach used in the present study may permit identification of diverse plasma
      detectable markers of atherosclerosis, and the subsequent non-invasive evaluation
      of in vivo arterial pathology.

PMID- 12801625
TI  - Non-high density lipoprotein cholesterol and coronary events during long-term
      statin treatment.

PMID- 12801626
TI  - Additional information on ApoB R3500Q mutation in Spain.

PMID- 12801628
TI  - The 'ORC cycle': a novel pathway for regulating eukaryotic DNA replication.
AB  - The function of the 'origin recognition complex' (ORC) in eukaryotic cells is to
      select genomic sites where pre-replication complexes (pre-RCs) can be assembled.
      Subsequent activation of these pre-RCs results in bi-directional DNA replication
      that originates at or close to the ORC DNA binding sites. Recent results have
      revealed that one or more of the six ORC subunits is modified during the G1 to S
      phase transition in such a way that ORC activity is inhibited until mitosis is
      complete and a nuclear membrane is assembled. In yeast, Cdk1/Clb phosphorylates
      ORC. In frog eggs, pre-RC assembly destabilizes ORC/chromatin sites, and ORC is
      eventually hyperphosphorylated and released. In mammals, the affinity of Orc1 for
      chromatin is selectively reduced during S-phase and restored during early G1
      phase. Unbound Orc1 is ubiquitinated during S-phase and in some cases degraded.
      Thus, most, perhaps all, eukaryotes exhibit some manifestation of an 'ORC cycle'
      that restricts the ability of ORC to initiate pre-RC assembly to the early G1
      phase of the cell cycle, making the 'ORC cycle' the premier step in determining
      when replication begins.

PMID- 12801629
TI  - Characterization of the mouse Abcc12 gene and its transcript encoding an ATP
      binding cassette transporter, an orthologue of human ABCC12.
AB  - We have recently reported on two novel human ABC transporters, ABCC11 and ABCC12,
      the genes of which are tandemly located on human chromosome 16q12.1 [Biochem.
      Biophys. Res. Commun. 288 (2001) 933]. The present study addresses the cloning
      and characterization of Abcc12, a mouse orthologue of human ABCC12. The cloned
      Abcc12 cDNA was 4511 bp long, comprising a 4101 bp open reading frame. The
      deduced peptide consists of 1367 amino acids and exhibits high sequence identity
      (84.5%) with human ABCC12. The mouse Abcc12 gene consists of at least 29 exons
      and is located on the mouse chromosome 8D3 locus where conserved linkage
      homologies have hitherto been identified with human chromosome 16q12.1. The mouse
      Abcc12 gene was expressed at high levels exclusively in the seminiferous tubules
      in the testis. In addition to the Abcc12 transcript, two splicing variants
      encoding short peptides (775 and 687 amino acid residues) were detected. In spite
      of the genes coding for both ABCC11 and ABCC12 being tandemly located on human
      chromosome 16q12.1, no putative mouse orthologous gene corresponding to the human
      ABCC11 was detected at the mouse chromosome 8D3 locus.

PMID- 12801630
TI  - The SCAN domain defines a large family of zinc finger transcription factors.
AB  - The SCAN domain is a highly conserved dimerization motif that is vertebrate
      specific and found near the N-terminus of C(2)H(2) zinc finger proteins (SCAN
      ZFP). Although the function of most SCAN-ZFPs is unknown, some have been
      implicated in the transcriptional regulation of growth factors, genes involved in
      lipid metabolism, as well as other genes involved in cell survival and
      differentiation. Here we utilize a bioinformatics approach to define the
      structures and gene locations of the 71 members of the human SCAN domain family,
      as well as to assess the conserved syntenic segments in the mouse genome and
      identify potential orthologs. The genes encoding SCAN domains are clustered,
      often in tandem arrays, in both the human and mouse genomes and are capable of
      generating isoforms that may affect the function of family members. Twenty-three
      members of the mouse SCAN family appear to be orthologous with human family
      members, and human-specific cluster expansions were observed. Remarkably, the
      SCAN domains in lower vertebrates are not associated with C(2)H(2) zinc finger
      genes, but are contained in large retrovirus-like polyproteins. Collectively,
      these studies define a large family of vertebrate-specific transcriptional
      regulators that may have rapidly expanded during recent evolution.

PMID- 12801631
TI  - Shotgun sequencing and microarray analysis of RDA transcripts.
AB  - Monitoring of differential gene expression is an important step towards
      understanding of gene function. We describe a comparison of the representational
      difference analysis (RDA) subtraction process with corresponding microarray
      analysis. The subtraction steps are followed in a quantitative manner using a
      shotgun cloning and sequencing procedure that includes over 1900 gene sequences.
      In parallel, the enriched transcripts are spotted onto microarrays facilitating
      large scale hybridization analysis of the representations and the difference
      products. We show by the shotgun procedure that there is a high diversity of gene
      fragments represented in the iterative RDA products (92-67% singletons) with a
      low number of shared sequences (<9%) between subsequent subtraction cycles. A non
      redundant set of 1141 RDA clones were immobilized on glass slides and the
      majority of these clones (97%) gave repeated good fluorescent signals in a
      subsequent hybridization of the labelled and amplified original cDNA. We observed
      only a low number of false positives (<2%) and a more than twofold differential
      expression for 32% (363) of the immobilized RDA clones. In conclusion, we show
      that by random sequencing of the difference products we obtained an accurate
      transcript profile of the individual steps and that large-scale confirmation of
      the obtained transcripts can be achieved by microarray analysis.

PMID- 12801632
TI  - Identification of 9 novel transcripts and two RGSL genes within the hereditary
      prostate cancer region (HPC1) at 1q25.
AB  - We applied a systematic bioinformatics approach, followed by careful manual
      inspection and experimental validation to identify additional expressed sequences
      located at the Hereditary Prostate Cancer Region (HPC1) between D1S2818 and
      D1S1642 on chromosome 1q25. All transcripts already described for the 1q25 region
      were identified and we were able to define 11 additional expressed sequences
      within this region (three full-length cDNA clone sequences and eight ESTs),
      increasing the total number of gene count in this region by 38%. Five out of the
      11 expressed sequences identified were shown to be expressed in prostate tissue
      and thus represent novel disease gene candidates for the HPC1 region. Here, we
      report a detailed characterization of these five novel disease gene candidates,
      their expression pattern in various tissues, their genomic organization and
      functional annotation. Two candidates (RGSL1 and RGSL2) correspond to novel
      members of the RGS family, which is involved in the regulation of G-protein
      signaling. RGSL1 and RGLS2 expression was detected by real-time polymerase chain
      reaction in normal prostate tissue, but could not be detected in prostate tumor
      cell lines, suggesting they might have a role in prostate cancer.

PMID- 12801633
TI  - Transfer RNA paralogs: evidence for genetic code-amino acid biosynthesis
      coevolution and an archaeal root of life.
AB  - A search has been performed on 2878 tRNA sequences from 60 different genomes in
      order to detect the existence of closely related 'alloacceptor' tRNAs accepting
      dissimilar amino acids that could be paralogs generated by gene duplications.
      This has led to the identification of extremely conserved tRNA(Phe)-tRNA(Tyr)
      pairs displaying as high as 94% identity between them, and also other potentially
      paralogous tRNA pairs in archaeal species. These paralogous pairs are enriched
      for amino acid pairs belonging to the same amino acid biosynthetic family, thus
      providing evidence for the coevolution of genetic code and amino acid
      biosynthesis. Overall, the genetic distances between alloacceptor tRNAs yield
      estimates of how closely clustered in sequence space are the tRNAs in a genome.
      Among 34 Bacteria, 18 Archaea and 8 Eukarya, Methanopyrus kandleri and Aeropyrum
      pernix have yielded the lowest alloacceptor distances and largest number of
      paralogous pairs. Based on a cluster-dispersion model of tRNA evolution, such
      tight alloacceptor clustering is a measure of primitiveness of tRNA genotypes,
      and places last universal common ancestor (LUCA) between the branches leading to
      these two archaea in the tRNA phylogenetic tree.

PMID- 12801634
TI  - Splicing in murine CABYR and its genomic structure.
AB  - Human calcium-binding tyrosine-phosphorylation regulated protein (CABYR) is a
      polymorphic, testis-specific, calcium binding protein that undergoes tyrosine
      phosphorylation during in vitro capacitation. A protein kinase A (PKA) regulatory
      subunit type II alpha (RII-alpha) homologous domain in the N-terminus,
      phosphorylation dependent Ca(++) binding isoforms, and localization to the
      principal piece of the human sperm tail suggest that CABYR may be involved in
      sperm motility. In this paper, four mouse orthologous cDNAs and the genomic DNA
      of CABYR were cloned, nucleotide and protein sequences of mouse and humans were
      compared, and the genomic organization of the mCABYR gene was analyzed. Human and
      mouse CABYR conserve potential functional motifs including a domain homologous to
      the dimerization interface of cyclic adenosine monophosphate dependent PKA RII
      alpha, 14 PXXP motifs, and regions of homology with extensins and src homology-3
      binding protein 1. mCABYR is arranged into six exons spanning about 14 kb of DNA.
      Mouse CABYR showed several similarities with human CABYR: (1) the protein was
      localized to the principal piece of mouse epididymal spermatozoa; (2) mouse CABYR
      has two coding regions (CR-A and CR-B), with 66 and 82% identity, respectively to
      human; and (3) mCABYR showed the presence of two testis-specific transcripts of
      approximately 1.4 and approximately 2.4 kb. Three murine splice variants were
      identified, two of which spliced into CR-B. Exon 4, present in all human and
      mouse variants and comprising 85% of CR-A appears suitable for targeted deletion.
      The overall 81% nucleotide identity between mouse and human CABYR, the common
      genomic organization, presence of similar testis-specific transcripts,
      localization in the principal piece of tail and occurrence of homologous splice
      variants indicate an authentic murine orthologue of CABYR has been identified.

PMID- 12801635
TI  - Molecular characterization of a new gene, CEAL1, encoding for a carcinoembryonic
      antigen-like protein with a highly conserved domain of eukaryotic translation
      initiation factors.
AB  - Carcinoembryonic antigen (CEA) is a complex immunoreactive glycoprotein belonging
      to a large and heterogeneous group of cross-reacting proteins known as the CEA
      gene family, which contains 29 genes/pseudogenes. CEA is used as a valuable serum
      tumor marker for monitoring response to therapy in patients with various solid
      tumors. Through the positional cloning approach we have identified and
      characterized a CEA-like gene (CEAL1), a novel member of the CEA multigene
      family. We have characterized the complete genomic structure of CEAL1, as well as
      one alternative splice variant and determined its chromosomal localization. The
      new gene is comprised of eight exons, with seven intervening introns and it is
      localized to chromosome 19q13.2 between the markers D19S574 and D19S219,
      approximately 60 kb upstream of the BCL3 gene. The protein-coding region of the
      gene is formed of 903 bp, encoding for a 300-amino-acid polypeptide with a
      predicted molecular weight of 32.6 kDa and isoelectric point of 5.74. The CEAL1
      protein contains two Immunoglobulin-like (Ig-like) transmembrane domains, which
      are present in most of the CEA proteins, as well as one highly conserved domain
      of eukaryotic translation initiation factors. The identified alternative spliced
      variant has one more exon of 134 bp. This splice variant is expected to encode
      for a truncated protein of 142 amino acids with the eIF5A domain and without Ig
      homology domain. CEAL1 mRNA is expressed in a variety of tissues, but highest
      levels are found in the prostate, uterus, fetal brain, mammary, adrenal gland,
      skeletal muscle, small intestine and kidney. CEAL1 is highly expressed in BT-474,
      BT20, T47D and, at much lower levels, in MCF7 breast cancer cell lines. The new
      gene is also highly expressed in the LNCaP prostate cancer cell line. The CEAL1
      gene was found to be down-regulated by dexamethasone in BT-474 breast cancer cell
      lines. Our data suggest that this gene is overexpressed in a subset of ovarian
      cancers which are clinically more aggressive.

PMID- 12801636
TI  - Integration of expression vectors into the ribosomal locus of Trypanosoma cruzi.
AB  - The expression vectors of the protozoan parasite Trypanosoma cruzi pRIBOTEX and
      pTREX harbor a ribosomal promoter that improves gene expression and clone
      selection. Interestingly, the solely presence of this 810 bp long sequence leads
      to the integration of these vectors into the ribosomal locus, even though
      circular plasmids are poorly recombinogenic. Initially, it was suggested that a
      174 bp long ribosomal-specific repeat element present in the ribosomal promoter
      region could be responsible for the genetic exchange. On the contrary, we
      demonstrate that recombination of pTREX occurs within a 86 bp long region located
      120 bp downstream the transcription start point (tsp1) of the ribosomal promoter,
      and it does not depend on the presence of the ribosomal repeat. We also
      determined that a 291 bp segment encompassing the tsp1 and the 86 bp long
      recombination region contains all necessary signals to drive transcription and
      complete recombination into the rRNA locus. Finally, we demonstrate that the
      integration of pTREX derived plasmids into the nuclear genome occurs within the
      first 5 h post-transfection, and that non-integrated copies are rapidly degraded.

PMID- 12801637
TI  - Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin
      receptor-like genes HTR3C, HTR3D and HTR3E.
AB  - For more than 50 years the serotonin system has been the subject of intense
      research. This has provided an exciting insight and led to the discovery of
      multiple drugs targeting serotonin receptors, metabolising enzymes and re-uptake
      sites. During the past few years researchers focussed especially on elucidating
      the complexity of different physiological actions in the serotonergic network. We
      have identified two novel human serotonin 5-hydroxytryptamine type 3 receptor
      like genes, HTR3D and HTR3E, by performing homology searches using the public
      human sequence databases and subsequently cloned the full length cDNAs by 5' and
      3' rapid amplification of complementary DNA ends. Mapping of HTR3D and HTR3E by
      hybridisation, polymerase chain reaction and fluorescence in situ hybridisation
      revealed that both genes together with HTR3C are clustered in a subinterval of
      less than 100 kb on chromosome 3q27. Comparative expression analysis of all HTR3
      genes, namely HTR3A, B, C, D and E showed HTR3D expression to be restricted to
      kidney, colon and liver and HTR3E expression to colon and intestine, whereas all
      other genes are widely expressed in many tissues including brain.

PMID- 12801638
TI  - Characterization of a SNF1 homologue from the phytopathogenic fungus Sclerotinia
      sclerotiorum.
AB  - In yeast, the SNF1 gene product is essential for the release of catabolic
      repression. We report the isolation and characterization of an SNF1 homologue
      from the necrotrophic pathogen Sclerotinia sclerotiorum. Ss snf1 encodes a 765
      amino-acid protein in which the catalytic domain has an overall identity with the
      yeast proteins varying from 55 to 76% while the C-terminal half of Ss SNF1 has a
      weak homology of about 20% with the yeast sequences. Reverse transcription
      polymerase chain reaction showed that its transcripts were weakly and
      constitutively expressed in planta and in vitro regardless of the nature of the
      carbon sources and of the presence or absence of glucose. Expression of Ss snf1
      in yeast cells allowed the snf1 mutant cells to utilize sucrose, raffinose or
      glycerol for growth while expression of the Ss snf1 catalytic domain did not
      restore growth on raffinose or glycerol. Ss SNF1 is structurally homologous to
      Snf1p, suggesting that the interactions between the kinase and the accessory
      subunits to activate the enzymatic complex are conserved in fungi.

PMID- 12801639
TI  - Structural and functional characterization of the zebrafish gene for glial
      fibrillary acidic protein, GFAP.
AB  - Glial fibrillary acidic protein, GFAP, is an astrocyte-specific member of the
      family of intermediate filament proteins which are involved in formation of the
      cytoskeletal structure. We here present a characterization of the zebrafish GFAP
      gene and corresponding protein. The zebrafish GFAP gene have the same exon-intron
      organization as the mammalian orthologoue genes. Comparison of the protein with
      mammalian GFAP shows that the amino acid sequence is highly conserved in the rod
      and tail domains whereas the head domain has diverged. Zebrafish GFAP exhibits
      functional characteristics of an intermediate filament protein such as
      dimerization potential, capacity to assembly into filaments, and cytoskeletal
      localization. Mutations in human GFAP have been associated with a severe
      childhood brain disorder called Alexander disease. Interestingly, the mutations
      affect preferentially amino acid residues of GFAP that are evolutionarily
      conserved. This indicates that a change of functionally core residues in GFAP is
      a prerequisite for the disease phenotype to develop and the initial steps in the
      pathogenesis may thus be modeled in zebrafish.

PMID- 12801640
TI  - Characterization of the human p11 promoter sequence.
AB  - p11 is expressed in many different cell types, and serves a variety of regulatory
      functions. In order to better understand the transcriptional control of this
      protein, the 5' promoter region of the human p11 gene was cloned and sequenced.
      After confirming the transcription start point (TSP) using 5' rapid amplification
      of cDNA ends analysis, the 5' promoter was analysed. The sequence lacks a TATA
      box, but contains a variety of putative regulatory elements. There are two GAS
      sites, two AP-1 sites, two overlapping Sp-1 sites, and a gamma-IRE site clustered
      between -1080 and -1450. There is another cluster of putative regulatory sites
      between the TSP and -550 which contains two Sp-1 sites, two AP-2 sites, one GAS
      site, one NF-kappaB site, an incomplete CAAT box (8/9) and an overlapping Sp-1/AP
      2 site at -17 to -26. Reporter gene constructs containing 4225 and 1498 bases 5'
      of the TSP demonstrated excellent unidirectional transcriptional activity in both
      constructs. Reporter genes containing serial 5' deletions were compared to the 
      1498 construct. The reporter gene which contained base pairs (bp) -36 to +89 had
      almost no activity. The reporter gene containing -188 to +89 had 50% of the -1498
      construct, indicating that this sequence contains at least the minimal promoter.
      The Sp-1/AP-2 site near the transcription start site was studied by
      electrophoretic mobility shift and reporter gene assays. Addition of HeLa cell
      nuclear extract to labeled double-stranded (ds) oligonucleotide containing this
      sequence resulted in a gel shift which was inhibited by excess unlabeled ds
      oligonucleotide and by a consensus cold Sp-1 ds oligonucleotide, indicating
      specific Sp-1 binding. Excess AP-2 or NF-kappaB ds oligonucleotide had no effect
      on nuclear protein binding to the sequence. Mutation of the p11 wild-type Sp-1/AP
      2 sequence eliminated both nuclear protein binding and the sequences ability to
      compete with native sequence for nuclear binding protein. A -1048 to +89 reporter
      construct containing a mutated Sp-1/AP-2 site resulted in a 40% decrease in
      transcriptional activity. Therefore, the 5' flanking sequence of the p11 gene
      exhibits promoter activity which may be localized to a variety of controlling
      regions, of which the proximal Sp-1/AP-2 site appears to be important for basal
      activity via its Sp-1 binding ability.

PMID- 12801641
TI  - Mouse sulphamidase gene: characterization of the promoter region of the gene and
      expression in mouse tissues.
AB  - Sulphamidase is a lysosomal enzyme necessary for the degradation of heparan
      sulphate. The deficiency of this hydrolase causes a disorder known as
      mucopolysaccharidosis type IIIA, characterized by a profound neurological
      deterioration. Human and mouse exon-intron structures were reported without any
      characterization of their promoter regions [DNA Res. 3 (1996) 269; Mamm. Genome
      11 (2000) 436]. The promoter region was isolated and characterized to understand
      the factors affecting the expression of mouse sulphamidase. The 5'-flanking
      region was shown to contain a GC-rich region and putative binding sites for the
      transcription factors SRY, MZF1 and Nkx-2.5 with no TATA or CAAT boxes present.
      The 5' region had promoter activity to drive luciferase gene expression in
      transfected COS cells. The transcription initiation site of mouse sulphamidase
      was mapped to a single adenine residue 355 bases upstream of ATG codon. Northern
      blot analysis revealed differential expression of a major transcript of 4.5 kb in
      all tissues examined. Finally, the 3'-untranslated region of the mouse
      sulphamidase gene was isolated and found to be longer than the region identified
      in the human gene.

PMID- 12801642
TI  - Genomic organization and promoter analysis of the Dnmt3b gene.
AB  - The Dnmt3b gene encodes a de novo DNA methyltransferase that is essential for
      normal mouse development. It is highly expressed in early embryos and embryonic
      stem (ES) cells but downregulated in most adult somatic tissues. To gain insight
      into the regulation of Dnmt3b, we have isolated a mouse genomic bacterial
      artificial chromosome clone that contains the Dnmt3b gene. Complete sequence
      analysis of the clone demonstrated that Dnmt3b consists of at least 24 exons and
      spans 38 kilobases. S1 nuclease analysis identified two adjacent transcriptional
      start sites located downstream of a unique TATA-like element in a CpG island.
      There was an unknown gene which we named mU(3) 17 kb upstream of the Dnmt3b
      locus, and it was transcribed ubiquitously and in the opposite direction of
      Dnmt3b. Transfection analysis revealed that the minimal promoter region
      containing an Sp1 site was active even in somatic cells, and that there were
      several repressor elements within 7.9 kb upstream of Dnmt3b downregulated this
      gene specifically in somatic cells but not in ES cells. These findings provide a
      basis for future detailed studies of the mechanisms controlling Dnmt3b
      expression.

PMID- 12801643
TI  - Identification of a larger form of the histone acetyl transferase Tip60.
AB  - The histone acetyl transferase Tat interactive protein 60kD (Tip60) plays major
      roles in the cellular response to extra- or intra-cellular signalling. Tip60
      activity appears to be tightly regulated in cells through post-translational
      modifications or subcellular localisation of the protein. In addition, several
      alternatively spliced forms of Tip60 have been described. We found here that in a
      significant proportion of cytoplasmic poly adenylated Tip60 mRNAs, the intron 1
      was not excised. Translation of this mRNA would predictably lead to the
      production of a longer Tip60 protein, containing a 33 amino acids insertion four
      amino acids after the ATG. By transient transfection experiments, we could
      demonstrate that this protein was significantly produced. Thus, taken together,
      our results indicate the existence of a longer Tip60 protein. Whether this
      protein could be differentially regulated and could play different roles than the
      classical Tip60 protein is an intriguing possibility.

PMID- 12801644
TI  - Molecular cloning of the pawn locus from Drosophila melanogaster.
AB  - Alleles of pawn have numerous morphological phenotypes, including dark deposits
      on the eye, truncated bristles, and semilethality. The gene encoding the pawn
      locus was cloned. The Pawn protein is predicted to be a large cell adhesion
      molecule with a single transmembrane domain, a short cytoplasmic tail and two
      extracellular epidermal growth factor (EGF)-like repeats. The identity of the
      pawn gene product was confirmed by sequencing the defects in four different pawn
      alleles. Analysis of cDNAs showed a complex genomic structure with two 5'
      untranslated exons and developmental-specific RNA splicing. The gene is expressed
      throughout development with highest expression found in the late embryonic and
      larval stages.

PMID- 12801645
TI  - Characterization of thioredoxin reductase genes (trr1) from Pneumocystis carinii
      and Pneumocystis jiroveci.
AB  - We have characterized the thioredoxin reductase (trr1) genes from Pneumocystis
      carinii and Pneumocystis jiroveci, and have demonstrated that multiple copies of
      an approximately 500 base pair fragment of the trr1 gene are present in P.
      carinii, but not in P. jiroveci. Thioredoxin reductases encoded by the full
      length genes have predicted molecular weights of approximately 35,000 and show
      high homology to yeast Trr1. An NADPH-binding domain with a putative redox active
      site CAVC as well as an flavin-adenine dinucleotide-binding domain are highly
      conserved in both proteins, which were 85% identical. The multicopy trr1 gene
      fragments in P. carinii are not transcribed or expressed. Duplication of the gene
      fragment likely occurred in conjunction with duplication of the kexin homologue,
      protease-1, which is located immediately upstream of the trr1 gene. Thioredoxin
      reductase, an enzyme implicated in the growth, survival and pathogenicity of
      certain microbes, could be a potential target for therapeutic intervention in
      Pneumocystis infection.

PMID- 12801646
TI  - Characterization and tissue expression of acidic fibroblast growth factor binding
      protein homologue in Drosophila melanogaster.
AB  - We have earlier reported a Drosophila protein, which aligned significantly with
      the amino acid sequence of the human acidic fibroblast growth factor
      intracellular binding protein (FIBP). In attempts to further elucidate the
      function of FIBP and its putative role in fibroblast growth factor (FGF)
      signaling we have cloned and characterized FIBP from Drosophila melanogaster
      (DrFIBP). Using comparative sequence analysis of Drosophila and human FIBP genes
      we demonstrate a remarkable conservation of their structural architecture
      suggesting that FIBP from vertebrates and insects are genuine homologues. Reverse
      transcriptase polymerase chain reaction analysis of FIBP mRNA from Drosophila
      revealed differential splicing by intron retention resulting in the production of
      three distinct FIBP transcripts. The retention of the intronic sequences
      introduces termination codons within the mature FIBP mRNA leading to premature
      termination of translation. Analysis of FIBP mRNA distribution in the fruit fly
      suggests that DrFIBP, like its mammalian homologue, is an abundant protein whose
      expression is maintained during embryonic, larval and adult stages. The spatial
      expression pattern investigated by whole mount embryo immunostaining reveals
      expression of FIBP in the developing tracheal system and in ventral midline
      cells, two known sites of FGF signaling in the fruit fly.

PMID- 12801647
TI  - Identification and characterization of two novel human SCAN domain-containing
      zinc finger genes ZNF396 and ZNF397.
AB  - We have identified two novel human SCAN domain genes ZNF396 and ZNF397, which are
      clustered within the region of chromosome 18q12. Three isoforms of ZNF396
      transcript, 1.5, 2.5 and 3.9-kb, are expressed highly in liver. Four isoforms of
      ZNF397 transcript, 1.7, 2.5, 7.0 and 9.0-kb, are expressed in a variety of
      tissues, with varying levels. The SCAN-(C(2)H(2))(X) genes encode two distinct
      proteins due to a unique alternative splicing mechanism. Both ZNF396-fu (full
      zinc fingers) and ZNF397-fu consist of a SCAN domain in the N-terminal region and
      many consecutive C(2)H(2) zinc finger repeats in the C-terminal region. ZNF396-nf
      (no zinc fingers) and ZNF397-nf encode 210 and 198 amino acids, respectively,
      containing the SCAN domain only. ZNF396-fu, ZNF396-nf, ZNF397-fu or ZNF397-nf can
      homo-associate, while ZNF396-fu hetero-associates with ZNF396-nf, and ZNF397-fu
      hetero-associates with ZNF397-nf. ZNF396-nf and ZNF397-nf polypeptides are
      expressed diffusely in the cells, while ZNF396-fu and ZNF397-fu polypeptides
      target specifically to the nuclei. ZNF396-fu, ZNF396-nf and ZNF397-nf can repress
      reporter gene transcription, with ZNF397-nf having the strongest repression
      activity. Deletion analysis revealed that ZNF397-fu is a transcriptional
      activator without its nine zinc finger repeats.

PMID- 12801649
TI  - Turnover of binding sites for transcription factors involved in early Drosophila
      development.
AB  - Despite the importance of cis-regulatory regions in evolution, little is know
      about their evolutionary dynamics. In this report, we analyze the process of
      evolution of binding sites for transcription factors using as a model a well
      characterized system, the Drosophila early developmental enhancers. We compare
      the sequences of eight enhancer regions for early developmental genes between
      Drosophila melanogaster and other two species, Drosophila virilis and Drosophila
      pseudoobscura, searching for the presence/absence of 104 biochemically verified
      binding sites from D. melanogaster. We also modeled the binding specificity of
      each binding site by the use of well-defined positional weight matrices (PWMs).
      The comparisons showed that turnover of binding sites seems to fit a molecular
      clock, at an approximate rate of 0.94% of gain/loss of binding sites per million
      years. This intense turnover affects both high and low affinity binding sites at
      the same extent. Furthermore, the subset of overlapping binding sites is also
      subjected to this high turnover. Conserved binding sites seem to be constrained
      to maintain not only location but also the exact sequence at each particular
      position. Finally, we detected a significant decrease in mean PWM scores for the
      D. virilis binding sites in the case of Hunchback. Possible explanations for this
      fact are discussed.

PMID- 12801651
TI  - Light-illuminated STM studies on photo-absorption in InAs nanowires.
AB  - We fabricated surface InAs nanowires along GaAs giant step structures on GaAs
      (110) vicinal substrates, and their photo-absorption properties were studied by
      scanning tunneling microscopy (STM) under light illumination. In photo-induced
      current detection, it was difficult to identify the photo-absorption signals in
      the InAs nanowires because of the electrical isolation of the surface
      nanostructures from the conductive substrate. On the other hand, optical response
      measurements of differential conductance under small AC bias modulation in STM
      enabled us to obtain the photo-absorption signals from the surface nanostructures
      with avoiding such an electrical isolation problem. We successfully observed
      optical response images of differential conductance with a clear contrast between
      InAs nanowires and surrounding GaAs region by the appropriate tuning of the
      illuminating photon energy to excite the InAs nanowires selectively.

PMID- 12801648
TI  - Characterization of the 5'-flanking region of the rat AJ18 gene.
AB  - Kruppel-associated box (KRAB) domains are present in one-third of all C(2)H(2)
      zinc finger containing proteins, making the KRAB/C(2)H(2) proteins one of the
      largest known families of putative transcription repressors. AJ18 has been
      identified as a novel KRAB/C(2)H(2) gene that is involved in the differentiation
      of osteogenic cells. To study the regulation of expression of the AJ18 gene, the
      5'-flanking region of the AJ18 gene was obtained by screening a rat genomic
      library. This region was sequenced, and the transcription start site mapped by
      primer extension. The AJ18 gene consists of at least four exons, the first exon
      coding for an unusually long 2.3 kb 5'-UTR region. A putative internal ribosome
      entry site, immediately upstream of the translation initiation site, is indicated
      from the complementarity of a 12 nucleotide sequence with a region in the rat 18S
      rRNA. Chimeric constructs encompassing the region surrounding the transcription
      start site (-77-+171), as well as constructs with additional 1.9 kb upstream from
      this region revealed strong transcriptional activity when ligated to a luciferase
      reporter gene and tested in transient transfection assays. This activity was lost
      on deletion of the 5'-flanking region to -77. In addition, transcriptional
      activity was progressively lost with the inclusion of downstream sequences
      extending into the 5'-UTR. Several known response elements for proteins such as
      Runx2, NFkappaB, Smads, Sp1, and Ets1 are retained within the conserved sequences
      of rat and mouse AJ18, which was retrieved from mouse genomic libraries.
      Interestingly, the transcriptional activity was approximately 100-fold higher in
      the osteocarcinoma cell line ROS 2.8/17 compared to the fibroblast-like
      C3H10T1/2. Notably, this is the first gene promoter from the large KRAB/C(2)H(2)
      zinc finger family of proteins to be identified and characterized.

PMID- 12801652
TI  - Spectroscopy of atomic chains with tunneling microscopy.
AB  - Recently, it has been possible to create metallic chains down to seven-atom long.
      This has two implications. Experimentally it is necessary to have algorithms that
      allow converting measured data into microscopic information as, for example,
      processing a current-voltage curve to obtain electronic density of states (DOS).
      From a theoretical standpoint, we have a new framework to test extant theories
      and to further develop them. With this in mind, we present a new theoretical
      solution to the problem of mapping scanning tunneling microscopy current-voltage
      curves into DOS-energy curves. Our model is based on a self-consistent solution
      to the quantum problem of electrons in the presence of an array of attractive
      centers. The problem, being simpler than its three-dimensional counterparts is
      solved exactly for DOS and for the current-voltage curves. The main results are
      that the current-voltage peaks at the position of the energies of the electron in
      the chain and, when an impurity is present in the chain, its chemical information
      can be extracted from the value of analytical curves.

PMID- 12801653
TI  - Dependence of tunneling current through a single molecule of phenylene oligomers
      on the molecular length.
AB  - The electrical properties of single phenylene oligomers were studied in terms of
      the dependence of the tunneling current on the length of the oligomers using self
      assembling techniques and scanning tunneling microscopy (STM). It is important to
      isolate single molecules in an insulating matrix for the measurement of the
      conductivity of the single molecule. We demonstrate here a novel self-assembled
      monolayer (SAM) matrix appropriate for isolation of the single molecules. A
      bicyclo[2.2.2]octane derivative was used for a SAM matrix, in which the single
      molecules were inserted at molecular lattice defects. The isolated single
      molecules of phenylene oligomers inserted in the SAM matrix were observed as
      protrusions in STM topography using a constant current mode. We measured the
      topographic heights of the molecular protrusions using STM and estimated the
      decay constant, beta, of the tunneling current through the single phenylene
      oligomers using a bilayer tunnel junction model.

PMID- 12801654
TI  - The effect of permanent dipole moments of adsorbates upon I-V characteristics of
      a bilayer tunneling junction between self-assembled monolayers on an Au(111)
      substrate and a gold tip.
AB  - It is important to understand an electronic property of an interface between an
      organic material and a metal electrode. In the present work, we measured current
      voltage (I-V) curves of self-assembled monolayers (SAMs) on Au(111) using a
      conducting atomic force microscope (AFM) with chemically modified Au-coated AFM
      tips. This contact resulted in a bilayer junction between the Au(111) substrate
      covered with one SAM and the Au-coated tip with the other SAM. An alkanethiol
      (octanethiol) and benzenemethanethiols with various terminal groups (-H, -CH(3), 
      Cl, -CF(3)) were used as the adsorbates. The shapes of the I-V curves depended on
      the terminal groups. This phenomenon was attributed to the change in the work
      function of gold due to different permanent dipole moments of the terminal
      groups.

PMID- 12801655
TI  - The differential reactivity of octahydridosilsesquioxane on Si(100)-2x1 and
      Si(111)-7x7: a comparative experimental study.
AB  - Scanning tunneling microscopy (STM), in conjunction with X-ray photoemission
      (XPS) and reflection-absorption infrared (RAIRS) spectroscopy, has been used to
      investigate the reaction of octahydridosilsesquioxane clusters (H(8)Si(8)O(12))
      on the Si(100)-2x1 and Si(111)-7x7 surfaces. The clusters exhibit a markedly
      different reactivity upon exposure to the two clean silicon surfaces. STM data is
      presented that, in conjunction with XPS and RAIRS data, provides numerous
      constraints upon possible geometries for the chemisorbed clusters. The sum of the
      data is consistent with a dissociative reaction mechanism on Si(100)-2x1,
      resulting in cluster attachment to the surface via a single vertex. Conversely,
      data of Si(111)-7x7 subject to a saturation exposure of H(8)Si(8)O(12) is
      presented that is highly suggestive of cluster decomposition on the surface.

PMID- 12801656
TI  - Scanning tunneling microscopy of 1, 2, and 3 layers of electroactive compounds.
AB  - Bilayer and trilayer organic films grown on Au(111) were studied by scanning
      tunneling microscopy (STM). Studies were carried out under UHV conditions with
      the sample cooled to either 80 or 100K. Cobalt(II)phthalocyanine [CoPc] was
      deposited from vapor onto Au(111), followed by vanadyl phthalocyanine, VOPc. CoPc
      coverages studied were 0.5 and 1 monolayer, while VOPc coverages were about 0.5
      monolayer. Constant current images were acquired at high tunneling gap
      resistance, of the order of 30GOmega. Two different physical structures were
      observed for VOPc on CoPc, and each had a characteristic I(V) curve indicating
      significantly different unoccupied state density. It is also demonstrated that
      the transmission factor for two layers of VOPc is not simply the product of the
      transmission factors for each layer.

PMID- 12801657
TI  - Scanning tunneling microscopy and spectroscopy investigations of QCA molecules.
AB  - Quantum-dot cellular automata (QCA), a computation paradigm based on the Coulomb
      interactions between neighboring cells. The key idea is to represent binary
      information, not by the state of a current switch (transistor), but rather by the
      configuration of charge in a bistable cell. In its molecular realization, the QCA
      cell can be a single molecule. QCA is ideally suited for molecular implementation
      since it exploits the molecule's ability to contain charge, and does not rely on
      any current flow between the molecules. We have examined using an UHV-STM some of
      the QCA molecules like silicon phthalocyanines and Fe-Ru complexes on Au (111)
      and Si (111) surfaces, which are suitable candidates for the molecular QCA
      approach.

PMID- 12801658
TI  - Ambient STM and in situ AFM study of nitrite reductase proteins adsorbed on gold
      and graphite: influence of the substrate on protein interactions.
AB  - Trimeric Achromobacter cycloclastes Cu-containing nitrite reductase (CuNIR)
      proteins adsorbed on gold and graphite have been studied by ambient STM and in
      situ AFM. STM resolves them individually and in layers, distinguishing the sub
      molecular individual units of the trimer. The Cu atoms are not visible to STM.
      STM shows that individual CuNIR denatures as it adsorbs on Au, although a
      deformed trimeric shape can be identified in some cases. CuNIR forms disordered
      layers on gold. On graphite, ordered self-assembled layers of CuNIR have been
      resolved by in situ AFM and ambient STM forming parallel rows whose separation
      distance corresponds to the size of one of the units of the trimer, 5nm. Ambient
      STM can achieve better resolution than in situ AFM in the images of the layers.
      We observe differences between domains showing the parallel row structure and
      unstructured parts of the CuNIR layer by in situ phase imaging AFM.

PMID- 12801659
TI  - AFM and STM study of beta-amyloid aggregation on graphite.
AB  - Atomic force microscopy (AFM) and scanning tunneling microscopy (STM) have been
      employed in situ and ex situ to directly study the aggregation of beta-amyloid(1
      42) (Abeta42) peptide on hydrophobic graphite. From in situ AFM images, Abeta42
      peptides were seen to aggregate into the sheets that preferred to three
      orientations with characteristic 3-fold symmetry (Proc. Natl. Acad. Sci. USA 96
      (1999) 3688). The sheets were formed by parallel narrow lines with a height of
      0.8-1.0nm and a width of 12-14nm. The narrow lines looked like beaded chains and
      have a right-handed axial periodicity. The high-resolution ex situ AFM and STM
      images showed that some fibrils of beta-amyloid had a characteristic domain
      texture, indicating they were formed through the association of protofibrils and
      monomers. The fibril containing lateral associated filaments that exhibited right
      handed twist was clearly observed in the STM image. These results provide
      important clues to study the detailed structure of beta-amyloid aggregates and
      the mechanism of the Abeta fibrils formation on hydrophobic surface.

PMID- 12801660
TI  - Nano-scale imaging of chromosomes and DNA by scanning near-field optical/atomic
      force microscopy.
AB  - Nano-scale structures of the YOYO-1-stained barley chromosomes and lambda-phage
      DNA were investigated by scanning near-field optical/atomic force microscopy
      (SNOM/AFM). This technique enabled precise analysis of fluorescence structural
      images in relation to the morphology of the biomaterials. The results suggested
      that the fluorescence intensity does not always correspond to topographic height
      of the chromosomes, but roughly reflects the local amount and/or density of DNA.
      Various sizes of the bright fluorescence spots were clearly observed in
      fluorescence banding-treated chromosomes. Furthermore, fluorescence-stained
      lambda-phage DNA analysis by SNOM/AFM demonstrated the possibility of nanometer
      scale imaging for a novel technique termed nano-fluorescence in situ
      hybridization (nano-FISH). Thus, SNOM/AFM is a powerful tool for analyzing the
      structure and the function of biomaterials with higher resolution than
      conventional optical microscopes.

PMID- 12801661
TI  - Probing nanoscale surface enhanced Raman-scattering fluctuation dynamics using
      correlated AFM and confocal ultramicroscopy.
AB  - We have studied the laser-excitation-intensity-dependent and Ag-nanocluster
      interstitial-site-dependent SERS intensity fluctuations under low molecule
      surface coverage of rhodamine 6G and cytochrome c. A new two-channel photon time
      stamping system coupled with atomic force microscopic (AFM), Raman spectroscopic,
      and imaging microscopy was developed and applied to record Raman intensity
      fluctuation trajectories at sub-microsecond resolution correlated with in situ
      characterization of the nanoparticle clusters. Our experimental results suggest
      that the nanoconfinement of the local electromagnetic-field enhancement and the
      interaction of the local field with the molecules, presumably under rotational
      motions, result in nano-Raman fluctuations. The SERS spectral fluctuation was
      pertinent to the nanoscale local enhancement and local interaction of the
      molecules with the surface when the surface coverage of the nanoparticles was
      less than a monolayer, and the nanoscale interstitial space controlled the finite
      number of molecules to contribute the microscopic Raman signal collected from a
      diffraction-limited focus spot. The fluctuation amplitude significantly decreased
      with the number of molecules confined at the nanolocal field. The nano-SERS
      fluctuation dynamics were both photo-induced and spontaneous for rhodamine 6G,
      but only the photo-induced component was observable for cytochrome c. The
      fluctuation dynamics were also found to be highly inhomogeneous at interstitial
      sites with heterogeneous geometries. To interpret the observed nano-SERS
      fluctuation dynamics, we used computer simulation of optical multiple scattering,
      based on multi-sphere scattering Mie theory, and rotational diffusion of
      molecules at an interstitial site, based on a random walk in orientation space.

PMID- 12801662
TI  - Recent advances in magnetic force microscopy.
AB  - During the past ten years magnetic force microscopy (MFM) has become probably the
      most powerful general-purpose method for magnetic imaging. MFM can be applied
      under various environmental conditions and requires only little sample
      preparation. Basic research on magnetic materials as well as the mentioned
      industrial applications create an increasing demand for high-resolution magnetic
      imaging methods. This contribution will review some new concepts which have been
      realized in the field of advanced probe preparation, based on electron beam
      methods in order to improve the spatial resolution beyond 100nm. It is shown that
      the advanced probes allow high-resolution imaging of magnetic fine structures
      within thin film permalloy elements exhibiting a complicated cooperative
      magnetization reversal process. These investigations are of importance for
      various concepts underlying modern magnetic data storage developments.
      Furthermore, we present some developments of MFM to suit the needs of the
      magnetic recording industry.

PMID- 12801663
TI  - Calibration of AFM cantilever spring constants.
AB  - In this paper we present two simple, reliable and readily applicable methods for
      calibrating cantilevers and measuring the thickness of thin gold films. The
      spring constant calibration requires knowledge of the Young's modulus, density of
      the cantilever and resonant frequency. The thickness of thin gold layers was
      determined by measuring changes in the resonant frequency and Q-factor of beam
      shaped AFM cantilevers before and after coating. The techniques for measuring the
      spring constant and thin film thickness provide accuracy on the order of 10-15%.

PMID- 12801664
TI  - Effects of temperature and pressure on microcantilever resonance response.
AB  - The variation in resonance response of microcantilevers was investigated as a
      function of pressure (10(-2)-10(6)Pa) and temperature (290-390K) in atmospheres
      of helium (He) and dry nitrogen (N(2)). Our results for a silicon cantilever
      under vacuum show that the frequency varies in direct proportion to the
      temperature. The linear response is explained by the decrease in Young's modulus
      with increasing the temperature. However, when the cantilever is bimaterial, the
      response is nonlinear due to differential thermal expansion. Resonance response
      as a function of pressure shows three different regions, which correspond to
      molecular flow regime, transition regime, and viscous regime. The deflection in
      flow transition regime resulting from thermal variation has minimal effect on
      frequency. The frequency variation of the cantilever is caused mainly by changes
      in the mean free path of gas molecules.

PMID- 12801665
TI  - Atomic force microscope characterization of a resonating nanocantilever.
AB  - An atomic force microscope (AFM) is used as a nanometer-scale resolution tool for
      the characterization of the electromechanical behaviour of a resonant cantilever
      based mass sensor. The cantilever is actuated electrostatically by applying DC
      and AC voltages from a driver electrode placed closely parallel to the
      cantilever. In order to minimize the interaction between AFM probe and the
      resonating transducer cantilever, the AFM is operated in a dynamic non-contact
      mode, using oscillation amplitudes corresponding to a low force regime. The
      dependence of the static cantilever deflection on DC voltage and of the
      oscillation amplitude on the frequency of the AC voltage is measured by this
      technique and the results are fitted by a simple non-linear electromechanical
      model.

PMID- 12801666
TI  - Studies of tip wear processes in tapping mode atomic force microscopy.
AB  - Tip integrity is crucial to atomic force microscope image quality. Tip wear not
      only compromises image resolution but also introduces artifacts. However, the
      factors that govern wearing have not been systematically studied. The results
      presented here of tip wearing on a rough titanium surface were determined by
      monitoring changes in tip shape and the evolution of histograms of complex
      surface curvatures under different control parameters. In contrast with the
      common assumption that operating at a low set point (the ratio of tapping
      amplitude to free oscillation amplitude) wears the tip quickly, we observed that
      a low set point actually minimizes tip wear on a hard surface regardless of the
      free amplitude. The results can be interpreted qualitatively with theoretical
      calculations based on momentum exchange at tapping impact. Operating at a low set
      point allows more robust scanning than with a high set point (tapping near free
      amplitude), providing a method to slow down tip wear. Another advantage of a low
      set point is that amplitude error grows faster than with a high set point by
      nearly an order of magnitude, permitting an increase in scanning speed.

PMID- 12801667
TI  - In-plane contributions to phase contrast in intermittent contact atomic force
      microscopy.
AB  - Contrast in the phase response of intermittent-contact atomic force microscopy
      (IC-AFM) reveals in-plane structural and mechanical properties of polymer
      monolayers. This result is unexpected, as IC-AFM has previously only been
      considered as a probe of out-of-plane properties. Until now, AFM measurements of
      nanoscale in-plane properties have employed contact mode techniques. In-plane
      property measurements are possible with intermittent contact AFM because there is
      a small but significant component of tip motion parallel to the sample surface.
      This in-plane component of tip displacement is virtually universal in AFM,
      implying that oscillating-tip techniques generally are sensitive to in-plane
      material properties. We present a simple Hertzian model of intermittent-contact
      AFM that includes such an in-plane displacement.

PMID- 12801668
TI  - Use of phase imaging in atomic force microscopy for measurement of viscoelastic
      contrast in polymer nanocomposites and molecularly thick lubricant films.
AB  - Phase contrast microscopy, using an atomic force microscope, is used to detect
      and quantify changes in composition across polymer nanocomposites and molecularly
      thick lubricated surfaces. The technique takes advantage of the contrast in
      viscoelastic (viscous energy dissipation) properties of the different materials
      across the surface. Some materials, especially polymers, are found to display
      viscoelastic behavior. For such materials, the strain response lags the stress by
      a phase angle that is characteristic of the material. In tapping (or intermittent
      contact) mode, phase angle contrast is found to be highly dependent on vibration
      amplitude and mean tip-to-sample distance (setpoint). Phase angle contrast seems
      to be a stronger function of viscoelastic properties at relatively high vibration
      amplitude and low mean tip-to-sample distance. In this regime the effects of
      sample deformation, and thus viscoelastic properties, are dominant. In these
      contrast images, low phase angle corresponds to materials with low viscoelastic
      properties. This technique was used to find fairly reproducible phase angle
      contrast for polyethylene terephthalate (PET) films with embedded ceramic
      particles, metal particle (MP) magnetic tape, and Si(100) with a nonuniform Z-15
      lubricant film. Very little correlation is found between phase angle images and
      friction force images for PET films with embedded ceramic particles and MP tape;
      phase angle images give information that cannot be obtained from topography or
      friction images. A numerical vibration model verifies that viscoelastic
      properties are dominant for high vibration amplitude and low mean tip-to-sample
      distance. For these conditions, the model also verifies that low phase angle
      corresponds to low viscoelastic properties.

PMID- 12801669
TI  - Imaging cobalt nanoparticles by amplitude modulation atomic force microscopy:
      comparison between low and high amplitude solutions.
AB  - In many situations of interest amplitude modulation AFM is characterized by the
      coexistence of two solutions with different physical properties. Here, we compare
      the performance of those solutions in the imaging of cobalt nanoparticles. We
      show that imaging with the high amplitude solution implies an irreversible
      deformation of the nanoparticles while repeated imaging with the low solution
      does not produce noticeable changes in the nanoparticles. Theoretical simulations
      show that the maximum tip-surface force in the high amplitude solution is about
      14nN while in the low amplitude solution is about -4nN. We attribute the
      differences in the high and low amplitude images to the differences in the
      exerted forces on the sample.

PMID- 12801670
TI  - A non-contact mode scanning force microscope optimised to image biological
      samples in liquid.
AB  - Given that biological samples are particularly soft in their natural state and
      that a liquid is the most difficult operating environment for non-contact mode
      scanning force microscopy, the development of a scanning force microscope that is
      optimised to image biological samples in vitro presents significant challenges.
      The performance of the instrument described here has been optimised for such an
      application by incorporating magnetic excitation and active-Q control of the
      cantilever. The application of this instrument has been validated by imaging
      monolayers of immobilised antibodies in liquid and achieving image qualities
      comparable to those achieved in air for such samples.

PMID- 12801671
TI  - Nonlinear dynamic perspectives on dynamic force microscopy.
AB  - Dynamic force microscopy (DFM) utilizes the dynamic response of a resonating
      probe tip as it approaches and retracts from a sample to measure the topography
      and material properties of a nanostructure. We present recent results based on
      nonlinear dynamical systems theory, computational continuation techniques and
      detailed experiments that yield new perspectives and insights into DFM.A dynamic
      model including van der Waals and Derjaguin-Muller-Toporov contact forces
      demonstrates that periodic solutions can be represented as a catastrophe surface
      with respect to the approach distance and excitation frequency. Turning points on
      the surface lead to hysteretic amplitude jumps as the tip nears/retracts from the
      sample. New light is cast upon sudden global changes that occur in the
      interaction potential at certain gap widths that cause the tip to "stick" to, or
      tap irregularly the sample. Experiments are performed using a tapping mode tip on
      a graphite sample to verify the predictions.

PMID- 12801672
TI  - Imaging of lactic acid bacteria with AFM--elasticity and adhesion maps and their
      relationship to biological and structural data.
AB  - The adhesion of lactic acid bacteria to the intestinal epithelium is one of the
      most important factors determining probiotic ability of a bacterial strain.
      Studying bacterial adhesion requires knowledge of the structure and properties of
      the bacterial surface, which can be studied by atomic force microscopy under
      native conditions. The observation of the surface topography of bacteria from the
      species Lactobacillus crispatus, L. helveticus and L. johnsonii shows major
      differences between bacteria having a crystalline-like protein layer as part of
      the cell wall and those without such layers. Force volume images calculated into
      elasticity and adhesion force maps of different bacterial strains show that L.
      crispatus and L. helveticus have a surface with a homogeneous stiffness with no
      adhesion events. This is most likely caused by the S-layer, which completely
      covers the surface of the bacteria. We infer that the absence of adhesion peaks
      is caused by the semi-crystalline character of such protein layers, in agreement
      with the results obtained from electron microscopy. Analysis of a number of L.
      johnsonii strains shows that these bacteria have surface properties which
      strongly differ from the L. crispatus and L. helveticus strains. For L. johnsonii
      DMS20533 and L. johnsonii ATCC33200 high adhesion forces are observed, which can
      be related to a surface rich in polysaccharides. L. johnsonii ATCC332 has lower
      adhesion forces compared to the other two and, furthermore, the surface
      topography shows depressions. We suppose that this strain has a surface pattern
      consisting of crystalline-like proteins alternating with polysaccharide-rich
      domains. The wide variety in surface properties of lactobacilli could well have
      wide-ranging implications for food processing and for health benefits.

PMID- 12801673
TI  - AFM imaging of bacteria in liquid media immobilized on gelatin coated mica
      surfaces.
AB  - Immobilization of particulates, especially biomolecules and cells, onto surfaces
      is critical for imaging with the atomic force microscope (AFM). In this paper,
      gelatin coated mica surfaces are shown to be suitable for immobilizing and
      imaging both gram positive, Staphylococcus aureus, and gram negative, Escherichia
      coli, bacteria in both air and liquid environments. Gelatin coated surfaces are
      shown to be superior to poly-L-lysine coated surfaces that are commonly used for
      the immobilization of cells. This cell immobilization technique is being
      developed primarily for live cell imaging of Rhodopseudomonas palustris. The
      genome of R. palustris has been sequenced and the organism is the target of
      intensive studies aimed at understanding genome function. Images of R. palustris
      grown both aerobically and anaerobically in liquid media are presented. Images in
      liquid media show the bacteria is rod shaped and smooth while images in air show
      marked irregularity and folding of the surface. Significant differences in the
      vertical dimension are also apparent with the height of the bacteria in liquid
      being substantially greater than images taken in air. In air immobilized
      bacterial flagella are clearly seen while in liquid this structure is not
      visible. Additionally, significant morphological differences are observed that
      depend on the method of bacterial growth.

PMID- 12801674
TI  - Atomic force microscopy of nanometric liposome adsorption and nanoscopic membrane
      domain formation.
AB  - Scanning probe microscopy studies of membrane fusion and nanoscopic structures
      were performed using hydrated single lipids and lipid mixtures. Extruded vesicles
      of DMPC and mixtures at various concentrations of DLPC, DPPC and cholesterol were
      deposited on freshly cleaved mica and studied in a fluid environment by AFM. The
      nanostructures formed by these extruded liposomes ranged from isolated
      unilamellar vesicles to flat sheet membranes and were marked influenced by
      thermodynamic phase behavior. For DMPC membrane, intact bilayers exhibited a
      phase transition process in agreement with large bilayer patches. In the DLPC,
      DPPC and cholesterol mixtures, nanoscopic domain diameters ranged from
      approximately 25 to 48nm with height differences of approximately 1.4nm; all
      values were lipid composition-dependent. Our data support and extend previous
      studies of microscopic domains and phase boundaries of the same mixtures in giant
      unilamellar vesicles determined by confocal light microscopy. Our approach for
      preparing and utilizing supported membrane structures is potentially relevant to
      studies of native cell membranes.

PMID- 12801675
TI  - Dynamic force microscopy imaging of native membranes.
AB  - We employed magnetic ACmode atomic force microscopy (MACmode AFM) as a novel
      dynamic force microscopy method to image surfaces of biological membranes in
      their native environments. The lateral resolution achieved under optimized
      imaging conditions was in the nanometer range, even when the sample was only
      weakly attached to the support. Purple membranes (PM) from Halobacterium
      salinarum were used as a test standard for topographical imaging. The hexagonal
      arrangement of the bacteriorhodopsin trimers on the cytoplasmic side of PM was
      resolved with 1.5nm lateral accuracy, a resolution similar to images obtained in
      contact and tapping-mode AFM. Human rhinovirus 2 (HRV2) particles were attached
      to mica surfaces via nonspecific interactions. The capsid structure and 2nm sized
      protein loops of HRV2 were routinely obtained without any displacement of the
      virus. Globular and filamentous structures on living and fixed endothelial cells
      were observed with a resolution of 5-20nm. These examples show that MACmode AFM
      is a favorable method in studying the topography of soft and weakly attached
      biological samples with high resolution under physiological conditions.

PMID- 12801676
TI  - Large fluctuations in the disassembly rate of microtubules revealed by atomic
      force microscopy.
AB  - Atomic force microscopy (AFM) in situ has been used to observe the cold
      disassembly dynamics of microtubules at a previously unrealised spatial
      resolution. Microtubules either electrostatically or covalently bound to
      aminosilane surfaces disassembled at room temperature under buffer solutions with
      no free tubulin present. This process was followed by taking sequential tapping
      mode AFM images and measuring the change in the microtubule end position as a
      function of time, with an spatial accuracy down to +/-20nm and a temporal
      accuracy of +/-1s. As well as giving average disassembly rates on the order of 1
      10 tubulin monomers per second, large fluctuations in the disassembly rate were
      revealed, indicating that the process is far from smooth and linear under these
      experimental conditions. The surface bound rates measured here are comparable to
      the rates for GMPCPP-tubulin microtubules free in solution, suggesting that
      inhibition of tubulin curvature through steric hindrance controls the average,
      relatively low disassembly rate. The large fluctuations in this rate are thought
      to be due to multiple pathways in the kinetics of disassembly with differing rate
      constants and/or stalling due to defects in the microtubule lattice. Microtubules
      that were covalently bound to the surface left behind the protofilaments
      covalently cross-linked to the aminosilane via glutaraldehyde during the
      disassembly process. Further work is needed to quantitatively assess the effects
      of surface binding on protofibril disassembly rates, reveal any differences in
      disassembly rates between the plus and minus ends and to enable assembly as well
      as disassembly to be imaged in the microscope fluid cell in real-time.

PMID- 12801678
TI  - Hybridisation of short DNA molecules investigated with in situ atomic force
      microscopy.
AB  - By introducing the complementary DNA (cDNA) strand to a molecular layer of short
      single stranded DNA (ssDNA), immobilised on a gold surface, we have investigated
      hybridisation between the two DNA strands through the technique of in situ atomic
      force microscopy (AFM). Before introduction of cDNA, the ssDNA molecular layer
      was modulated with the spacer molecule mercaptohexanol (MCH), which makes the
      ssDNA molecules more accessible for hybridisation. With in situ AFM, we have
      monitored the formation of a smooth, mixed molecular layer containing ssDNA and
      MCH. Furthermore, the hybridisation between the two DNA strands has been studied.
      Introduction of the cDNA strand resulted in an increase in smoothness and
      thickness of the molecular layer. Both the increase in order and thickness of the
      molecular layer can be expected if hybridisation occurs, since double stranded
      DNA molecules have a more rigid and elongated structure than ssDNA molecules.

PMID- 12801677
TI  - Imaging stretched single DNA molecules by pulsed-force-mode atomic force
      microscopy.
AB  - The effect of a surface water layer on DNA strands deposited on a substrate was
      studied by atomic force microscopy (AFM). DNA molecules were deposited and
      stretched on chemically modified glass coverslips by a molecular combing method.
      Lambda bacteriophage DNA molecules were aligned on the organosilane-modified
      substrate surfaces by chemical and physical adsorption during the molecular
      combing. The combed DNA molecules were observed in humidity-controlled air and in
      aqueous solutions by pulsed-force-mode AFM (PFM-AFM). Chemical modification of
      cantilevers with an Au-coated tip by organothiol compounds was also applied to
      DNA observation. Mapping adhesive forces in aqueous media was useful to
      discriminate chemically the DNA strands from the substrate surface. The results
      suggest that PFM-AFM can be used widely to image the stretched DNA molecules on
      the silane-modified substrates.

PMID- 12801679
TI  - Intersegmental interactions in supercoiled DNA: atomic force microscope study.
AB  - Intersegmental interactions in DNA facilitated by the neutralization of
      electrostatic repulsion was studied as a function of salt concentration and DNA
      supercoiling. DNA samples with defined superhelical densities were deposited onto
      aminopropyl mica at different ionic conditions and imaged in air after drying of
      the samples. Similar to hydrodynamic data, we did not observe a collapse of
      supercoiled DNA, as proposed earlier by cryo-EM studies. Instead, the formation
      of the contacts between DNA helices within supercoiled loops with no visible
      space between the duplexes was observed. The length of such close contacts
      increased upon increasing NaCl concentration. DNA supercoiling was a critical
      factor for the stabilization of intersegmental contacts. Implications of the
      observed effect for understanding DNA compaction in the cell and for regulation
      DNA transactions via interaction of distantly separated DNA regions are
      discussed.

PMID- 12801680
TI  - Highly ordered thin films prepared with octabutoxy copper phthalocyanine
      complexes.
AB  - Langmuir-Blodgett (LB) films of copper (II) 1,4,8,11,15,18,22,25
      octabutoxyphthalocyanine, nCuPc(OBu)(8), (non-peripheral substitution) and copper
      (II) 2,3,9,10,16,17,23,24-octabutoxyphthalocyanine, pCuPc(OBu)(8), (peripheral
      substitution), were fabricated and characterized by optical spectroscopy and
      scanning probe microscopy. The LB films were transferred onto hydrophilic
      substrates by vertical dipping. Although they posses relatively short polar
      substituents both compounds form smooth, uniform, dense, and highly stable LB
      monolayers composed of linear arrays of cofacial oligomers. The long range
      discotic assemblies of LB and spun cast films of pCuPc(OBu)(8) and nCuPc(OBu)(8)
      posses physical and chemical properties favorable for molecular electronic device
      application.

PMID- 12801681
TI  - Silatrane-based surface chemistry for immobilization of DNA, protein-DNA
      complexes and other biological materials.
AB  - The procedure of surface functionalization based on the use of 1-(3
      Aminopropyl)silatrane (APS) instead of our early procedure utilizing aminopropyl
      triethoxy silane (APTES) is described. Unlike APTES, APS is less reactive and
      extremely resistant to hydrolysis and polymerization at neutral pH. The kinetics
      of DNA adsorption to APS-mica was studied. The results are consistent with a
      diffusion controlled mechanism suggesting that DNA molecules bind irreversibly
      with the surface upon immobilization. This conclusion is supported by the data on
      imaging of supercoiled DNA, the labile conformations of which are very sensitive
      to the conditions at the surface-liquid interface. In addition, we demonstrated
      directly that the segments of DNA molecules could move along the surface if the
      sample is imaged in aqueous solution without drying of the sample. Using the time
      lapse mode of AFM imaging we visualized the transition of purine-pyrimidine
      sequence in supercoiled DNA from intramolecular triple-helical conformation (H
      form) into the B-helix upon the change of pH from acidic (pH 5) to neutral. The
      mechanisms of the H-to-B transitions and the correlation of the local structural
      transitions with a global DNA conformation are discussed.

PMID- 12801682
TI  - Optimisation of sample preparation methods for air imaging of ocular mucins by
      AFM.
AB  - The addition of cations to the imaging buffer for AFM has been previously shown
      to improve the binding of biological molecules to mica. Investigations were
      carried out to find the concentration of NiCl(2) required to immobilize mucin
      molecules on a freshly cleaved mica surface, for imaging using intermittent
      contact in air. Drop-deposition of samples prepared in HEPES buffer with 1, 2 and
      5mM NiCl(2) revealed the sensitivity of the mucin molecules to salt. Dialysis of
      the mucin solutions dramatically reduced the amount of salt present and allowed
      single molecules to be imaged, revealing a variation in thickness along their
      length. Spray deposition of the same mucin solutions produced single molecules
      that, although less affected by co-adsorbed salt, showed a degree of self
      folding. This shows the sensitive balance between HEPES and NiCl(2) required for
      successful imaging of the sub-molecular features of individual mucin molecules.

PMID- 12801684
TI  - A study of topographic effects on chemical force microscopy using adhesive force
      mapping.
AB  - Origins of peak broadening in a histogram of measured adhesive forces were
      studied. The adhesive forces were measured in water by pulsed-force-mode atomic
      force microscopy. One sample was prepared by a microcontact printing method on a
      sputtered gold film with fine grains, on which CH(3)- and COOH-terminated regions
      were produced. Gold surfaces of other samples were chemically modified
      homogeneously by a self-assembling method in solution. Their surfaces were,
      however, topographically different, i.e. (i) an Au(111)-terrace-rich gold film
      prepared by vacuum vapor deposition at high temperature and (ii) sputtered gold
      films on cover glass with different grain sizes obtained by different deposition
      time. These sample surfaces and the probe tip surface were all CH(3)-terminated
      by self-assembled monolayers with CH(3)(CH(2))(19)SH. The main origin of peak
      broadening in the histogram was the topographic effect. Namely, the change in the
      grain sizes and the change in multiplicity of contacts between the tip and
      convexities of the grains resulted in the distribution of the observed adhesive
      forces.

PMID- 12801683
TI  - Chiral discrimination of basic and hydrophobic molecules by chemical force
      spectroscopy.
AB  - Chemical force spectroscopy (CFS) is becoming a powerful technique with which to
      measure intermolecular forces. The prime advantage over other techniques is the
      ability to map spatial distribution of ligands on the surface. We have used CFS
      to explore the binding force of a variety of different chiral molecules in order
      to understand more about the nature of what is a fundamental aspect of chemical
      biology and of central importance in pharmacology.

PMID- 12801685
TI  - Lateral force microscopy profiles for amorphous potentials.
AB  - In this work, the lateral force profiles of the scanning force microscope tip on
      an amorphous surface were simulated with the use of an independent oscillator
      model. The correlation between the lateral force profiles and the surface
      potential were studied as a function of the tip-surface normal force and relative
      scanning velocity. It is shown that the microscope resolution is governed by the
      quotient between the average potential interaction energy and the average elastic
      energy stored before the jumps. We show that there is an optimal velocity with
      which the scanning tip better senses the surface potential and we present its
      scaling laws.

PMID- 12801686
TI  - Nanotribological characterization of molecularly thick lubricant films for
      applications to MEMS/NEMS by AFM.
AB  - Molecularly thick perfluoropolyether (PFPE) films are considered to be good
      protective films for micro/nanoelectromechanical systems (MEMS/NEMS) to reduce
      stiction, friction, and improve their durability. Understanding the
      nanotribological performance and mechanisms of these films are quite important
      for efficient lubrication for MEMS/NEMS devices. These devices are used in
      various operating environments and their effect on friction, adhesion and
      durability needs to be clarified. For this purpose, mobile and chemically bonded
      PFPE films were deposited by dip coating technique. The friction and adhesion
      properties of these films were characterized by atomic force microscopy (AFM).
      The effect of rest time, velocity, relative humidity, and temperature on
      nanotribological properties of these films was studied. Durability of these films
      was also measured by repeated cycling tests. The adhesion, friction mechanisms of
      PFPE at molecular scale, and the mechanisms of the effect of operating
      environment and durability are subject of this paper. This study found that
      adsorption of water, formation of meniscus and its change during sliding,
      viscosity, and surface chemistry properties play a big role on the friction,
      adhesion, and durability of the lubricant films.

PMID- 12801687
TI  - Molecular interaction studies of hemostasis: fibrinogen ligand-human platelet
      receptor interactions.
AB  - The interactions between fibrinogen ligands and platelet receptor
      alpha(IIb)beta(3) were studied under physiological conditions by atomic force
      microscopy (AFM). Two linear peptide sequences in fibrinogen, RGD and
      HHLGGAKQAGDV, play central roles in the regulation of hemostasis and thrombosis
      by facilitating adhesion and aggregation of platelets. In order to measure the
      interactions (i.e., debonding force), oligopeptides, GSSSGaaa, where aaa is 
      RGDSPA or -HHLGGAKQAGDV, were synthesized and grafted on to the surface of AFM
      probe tips. The interaction forces between a peptide-modified AFM probe tip and
      platelet surface were determined from pN to nN levels using AFM force
      measurements. Our results show that the zero kinetic off-rate, K(off)(0), for
      RGDSPA is significantly smaller than that for HHLGGAKQAGDV, under the
      consideration of flexible receptor surfaces. From our analysis, the K(off)(0),
      the single molecular binding energy E(b), and the transition state x(b), were
      extracted from the data, and estimated to be 1.53s(-1), -2.64x10(-20)J and 1.03A
      for the RGD-alpha(IIb)beta(3) system, and 47.58s(-1), 2.67x10(-20), 1.09A for the
      HHLGGAKQAGDV-alpha(IIb)beta(3) system, respectively.

PMID- 12801688
TI  - Mapping of the receptor-associated protein (RAP) binding proteins on living
      fibroblast cells using an atomic force microscope.
AB  - The distribution of the receptor-associated protein (RAP) binding protein and the
      adhesion forces between RAP and its binding protein on living fibroblast cells
      were examined using an atomic force microscope (AFM). The distribution of RAP
      binding protein was obtained on 256 (16x16) locations in 2x2 micro m sections
      over the surface of living cells. The adhesion forces between RAP and the binding
      protein were measured with an AFM tip functionalized with RAP. In the presence of
      RAP in the scanning solution, the number of force curves with large adhesion
      force decreased. These results indicate that the adhesive forces observed here
      represent specific binding between RAP and the binding protein. This method will
      be a useful application of AFM to examine receptors on cell surfaces in high
      resolution.

PMID- 12801689
TI  - Quantification of cell adhesion force with AFM: distribution of vitronectin
      receptors on a living MC3T3-E1 cell.
AB  - Distribution of vitronectin (VN) receptors on a living murine osteoblastic cell
      was successfully measured by atomic force microscopy (AFM). First, the
      distribution of the integrin beta(5) subunit which constitutes a part of the VN
      receptor on the cell was confirmed by conventional immunohistochemistry after
      fixing the cell. To visualize the distribution of the receptor on a living cell
      by an independent and potentially a more quantitative method, the AFM was used
      with a microbead attached to the cantilever tip to increase the area of contact
      and VN was immobilized on the microbead. Force measurements were then performed
      over a large area of a living murine osteoblastic cell using the microbead
      covered with VN.

PMID- 12801690
TI  - An embedded polymer piezoresistive microcantilever sensor.
AB  - We have developed a new type of chemical microsensor based on piezoresistive
      microcantilever technology. In this embedded polymer microsensor, a
      piezoresistive microcantilever is partially "embedded" into a polymeric material.
      Swelling of the polymer upon analyte exposure is measured as a simple resistance
      change in the embedded cantilever. Arrays of these sensors, each employing a
      different polymeric material, provide for the identification of a wide range of
      chemical vapor analytes. Advantages of this system over previous "surface"
      piezoresistive microcantilever chemical sensors include enhanced mechanical
      simplicity (no mechanical approach necessary), greater resistance to shock or
      movement, and lower cost.

PMID- 12801691
TI  - Optimised cantilever biosensor with piezoresistive read-out.
AB  - We present a cantilever-based biochemical sensor with piezoresistive read-out
      which has been optimised for measuring surface stress. The resistors and the
      electrical wiring on the chip are encapsulated in low-pressure chemical vapor
      deposition (LPCVD) silicon nitride, so that the chip is well suited for operation
      in liquids. The wiring is titanium silicide which-in contrast to conventional
      metal wiring-is compatible with the high-temperature LPCVD coating process.

PMID- 12801692
TI  - Quantum size aspects of the piezoresistive effect in ultra thin piezoresistors.
AB  - Proximal probe sensors with an ability to detect extremely small forces (10(-15)
      10(-18)N) play significant role in scanning probe microscopy applications. The
      detection of extremely low forces, require producing micromachined cantilevers
      with as small as possible spring constants, which is considered by the
      optimization of the sensor design. In the last year many papers describing the
      fabrication process of producing ultrathin cantilevers (below 100nm) with
      integrated piezoresistors for deflection read-out have been published. In the
      case of such cantilevers the required thickness of piezoresistors is in the range
      of 50nm. From a quantum mechanical point of view, an electrical carrier transport
      confinement in direction perpendicular to the cantilever surface can be expected
      and in this manner we have to consider the quantum size effect. The goal of the
      project described in this paper is to calculate and determine the piezoresistive
      coefficients in p type Si thin (under 50nm) piezoresistors taking into account
      the quantum size effect and to compare them with the corresponding coefficients
      for bulk material. The calculation of the band structure will use the
      mathematical apparatus of an exact analytical diagonalization six-band k.p model,
      modified with the envelope function approximation. The behaviour of the thin
      piezoresistors employed as integrated deflection read-out will be also discussed.
      Moreover, critical issues in the realization of piezoresistors formed by MOS
      transistor channel will be presented.

PMID- 12801693
TI  - Calibration and examination of piezoresistive Wheatstone bridge cantilevers for
      scanning probe microscopy.
AB  - This paper describes the method of determining the force constant and
      displacement sensitivity of piezoresistive Wheatstone bridge cantilevers applied
      in scanning probe microscopy (SPM). In the procedure presented here, the force
      constant for beams with various geometry is determined based on resonance
      frequency measurement. The displacement sensitivity is measured by the deflection
      of the cantilever with the calibrated piezoactuator stage. Preliminary results
      show that our method is capable of measuring the force constant of Wheatstone
      bridge cantilevers with an accuracy of better than 5% and this is used as
      feedback for improvement of sensor micromachining process.

PMID- 12801694
TI  - Manipulation of microcantilever oscillations.
AB  - Experimental observation of self-sustaining oscillations via a delayed feedback
      system is presented for a rectangular silicon microcantilever. The system is
      modeled as one and two-dimensional damped oscillator and the resulting delay
      differential equations are studied in frequency and time domain. The shortcomings
      of each model are outlined, and an improved formulation of the dynamics of the
      cantilever is presented.

PMID- 12801695
TI  - Observation of Knudsen effect with microcantilevers.
AB  - The Knudsen effect is estimated theoretically and observed experimentally using a
      U-shaped silicon microcantilever. Though Knudsen forces are extremely small in
      most cases involving microcantilevers, there exist situations where these forces
      can be significant and may be important in atomic force microscopy and in
      microelectromechanical systems (MEMS). The criteria for the presence of Knudsen
      forces are outlined and an analytical expression in the form of a linear function
      of the pressure is given for the force in the free molecular regime. The
      experimental results display peaks in the transitional regime while varying
      linearly in the molecular regime.

PMID- 12801696
TI  - A new cantilever system for gas and liquid sensing.
AB  - A novel setup for gas and liquid sensing was developed and tested. It is based on
      both detection of frequency shift and of bending of micro-cantilevers to measure
      mass changes as well as viscosity changes. To drive the cantilevers new
      electrostatic and magnetic actuations were invented with a closed feed-back loop
      which forces the cantilever to oscillate always at its resonance frequency. The
      oscillation is detected via the beam-deflection technique. By measuring the DC
      signal of the photodiode the static bending of the cantilever can be monitored
      simultaneously. The closed feed-back loop propagates a very stable oscillation at
      the resonance frequency and gives a strong increase in the quality factor
      compared to a system without such feed-back loop. Furthermore, it is possible to
      operate this cantilever transducer system in liquids. These cantilever sensors
      hence, show the potential for use in easy-to-use and highly sensitive sensor
      systems for gas and liquid phase chemical and biochemical sensing.

PMID- 12801697
TI  - Enhancing chemi-mechanical transduction in microcantilever chemical sensing by
      surface modification.
AB  - The use of chemically selective thin-film coatings has been shown to enhance both
      the chemical selectivity and sensitivity of microcantilever (MC) chemical
      sensors. As an analyte absorbs into the coating, the coating can swell or
      contract causing an in-plane stress at the associated MC surface. However, much
      of the stress upon absorption of an analyte may be lost through slippage of the
      chemical coatings on the MC surface, or through relaxation of the coating in a
      manner that minimizes stress to the cantilever. Structural modification of MC
      chemical sensors can improve the stress transduction between the chemical coating
      and the MC. Surfaces of silicon MC were modified with focused ion beam milling.
      Sub-micron channels were milled across the width of the MC. Responses of the
      nanostructured, coated MCs to 2,3-dihydroxynaphthalene and a series of volatile
      organic compounds (VOCs) were compared to smooth, coated MCs. The analytical
      figures of merit for the nanostructured, coated MCs in the sensing of VOCs were
      found to be better than the unstructured MCs. A comparison is made with a
      previously reported method of creating disordered nanostructured MC surfaces.

PMID- 12801698
TI  - Monitoring the chemical changes in Pd induced by hydrogen absorption using
      microcantilevers.
AB  - The reactivity of the palladium shaped as a microcantilever is investigated as a
      function of the hydrogen stoichiometry. A small cell holding the microcantilever
      is designed to monitor the deflection and the flexural resonance response from
      high vacuum to a hydrogen gas pressure of several bars. The measurements show
      that the Young's modulus is accurate if the cantilever is thick enough to be
      described by a continuum mechanics approach. The orientation distribution
      function of the palladium grains determined by X-ray diffraction enables to
      correlate Young's modulus measured using microcantilevers with the elastic
      constant tensor issued from the literature. The surface stress induced by the
      dissociation of H(2) in palladium surface depends mainly on the cantilever cross
      section. Cantilever response was found to be extremely sensitive to both the
      palladium lattice expansion induced by the insertion of hydrogen atoms into
      octahedral sites of palladium and the electronic affinity between palladium and
      hydrogen.

PMID- 12801699
TI  - Adsorption-desorption characteristics of explosive vapors investigated with
      microcantilevers.
AB  - Understanding the kinetics of adsorption and desorption of explosive vapors such
      as TNT from surfaces is important in the design of sensors. We report for the
      first time, the adsorption-desorption characteristics of TNT from a Si
      microcantilever exposed to vapors of TNT. It was observed that TNT readily sticks
      to the exposed Si surface with the adsorption kinetics showing an initial
      exponential behavior followed by roughly linear kinetics. It was also observed
      that for cantilever temperatures close to room temperature, TNT desorbs
      spontaneously from the surface with decaying exponential kinetics. Based on the
      known equilibrium partial vapor pressures of TNT, the "effective" sticking
      coefficient for the silicon oxide surface at room temperature under the
      experimental conditions was calculated to be about 0.02. This information can be
      very useful in the design of sensors and that of vapor-delivery systems.

PMID- 12801700
TI  - Performance of interdigitated nanoelectrodes for electrochemical DNA biosensor.
AB  - An electrochemical methodology for bio-molecule sensing using an array of well
      defined nanostructures is presented. We describe the fabrication by e-beam
      lithography of nanoelectrodes consisting of a 100 micro m x 50 micro m area
      containing interdigitated electrodes of 100 nm in width and interelectrode
      distance of 200 nm. Sensitivity and response time of the nanoelectrodes are
      compared to the responses of macro- and microelectrodes. The specificity of the
      sensor is studied by modifying the gold electrodes with DNA. The technique
      enables to characterize both single and double-stranded DNA of 15 nucleotides. A
      special electrochemical cell is adapted to control the temperature and measure
      the DNA concentration by UV analysis. The electrochemical method requires no
      label on the DNA, only redox mediators were used.

PMID- 12801701
TI  - IR imaging using uncooled microcantilever detectors.
AB  - Uncooled bimaterial microcantilever detectors were fabricated and used to obtain
      infrared (IR) images of objects at temperatures ranging from room temperature to
      a few hundred degrees C. Images were obtained using both single 50 micro m x 50
      micro m microcantilever IR detectors and arrays of microcantilever detectors.
      Thermal radiation from the target object was imaged onto the detector and the
      resulting temperature change caused microcantilever bending due to the bimaterial
      effect. This micromechanical bending was measured using two different non-contact
      optical readout techniques and IR images were obtained. A smaller size (20 micro
      m x 20 micro m) microcantilever IR detector was also used to capture IR images of
      near room temperature objects.

PMID- 12801702
TI  - Detection and differentiation of biological species using microcalorimetric
      spectroscopy.
AB  - We report on the application of infrared (IR) microcalorimetric spectroscopy (
      micro -CalSpec) to the identification and detection of trace amounts of
      biological species. Our approach combines principles of photothermal IR
      spectroscopy with ultrasensitive microcantilever (MC) thermal detectors. We have
      obtained photothermal IR spectra for DNA and RNA bases and for Bacillus Cereus
      (an anthrax simulant) in the wavelength range of 2.5-14.5 micro m (4000-690 cm(
      1)). The measurements are accomplished by absorbing biological materials directly
      on a MC thermal detector. The main advantage of the developed micro -CalSpec is
      its unprecedented sensitivity as compared to any of the previously explored IR
      techniques, including FTIR and photothermal FTIR methods. Our results demonstrate
      that <10(-9)g of a biological sample is sufficient to obtain its characteristic
      micro -CalSpec spectrum that contains information-rich chemical (vibrational)
      signatures. This opens up a new opportunity to create inexpensive high-throughput
      analytical systems for biochemical detection.

PMID- 12801703
TI  - AFM lithography of aluminum for fabrication of nanomechanical systems.
AB  - Nanolithography by local anodic oxidation of surfaces using atomic force
      microscopy (AFM) has proven to be more reproducible when using dynamic, non
      contact mode. Hereby, the tip/sample interaction forces are reduced dramatically
      compared to contact mode, and thus tip wear is greatly reduced. Anodic oxidation
      of Al can be used for fabricating nanomechanical systems, by using the Al oxide
      as a highly selective dry etching mask. In our experiments, areas as large as 2
      micro m x 3 micro m have been oxidized repeatedly without any sign of tip-wear.
      Furthermore, line widths down to 10nm have been routinely obtained, by
      optimization of AFM parameters, such as tip/sample distance, voltage and scan
      speed. Finally, AFM oxidation experiments have been performed on CMOS processed
      chips, demonstrating the first steps of fabricating fully functional
      nanomechanical devices.

PMID- 12801704
TI  - Feasibility of tunable MEMS photonic crystal devices.
AB  - Periodic photonic crystal structures channel electromagnetic waves much as
      semiconductors/quantum wells channel electrons. Photonic bandgap crystals (PBC)
      are fabricated by arranging sub-wavelength alternating materials with high and
      low dielectric constants to produce a desired effective bandgap. Photons with
      energy within this bandgap cannot propagate through the structure. This property
      has made these structures useful for microwave applications such as frequency
      selective surfaces, narrowband filters, and antenna substrates when the
      dimensions are on the order of millimeters. They are also potentially very
      useful, albeit much more difficult to fabricate, in the visible/near-infrared
      region for various applications when the smallest dimensions are at the edge of
      current micro-lithography fabrication tools. We micro-fabricated suspended free
      standing micro-structure bridge waveguides to serve as substrates for PBC
      features. These micro-bridges were fabricated onto commercial silicon-on
      insulator wafers. Nanoscale periodic features were fabricated onto these micro
      structure bridges to form a tunable system. When this combined structure is
      perturbed, such as mechanical deflection of the suspended composite structure at
      resonance, there can be a realtime shift in the material effective bandgap due to
      slight geometric alterations due to the induced mechanical stress. Extremely high
      resonance frequencies/device speeds are possible with these very small dimension
      MEMS.

PMID- 12801705
TI  - Mechanical characterization of micro/nanoscale structures for MEMS/NEMS
      applications using nanoindentation techniques.
AB  - Mechanical properties of micro/nanoscale structures are needed to design reliable
      micro/nanoelectromechanical systems (MEMS/NEMS). Micro/nanomechanical
      characterization of bulk materials of undoped single-crystal silicon and thin
      films of undoped polysilicon, SiO(2), SiC, Ni-P, and Au have been carried out.
      Hardness, elastic modulus and scratch resistance of these materials were measured
      by nanoindentation and microscratching using a nanoindenter. Fracture toughness
      was measured by indentation using a Vickers indenter. Bending tests were
      performed on the nanoscale silicon beams, microscale Ni-P and Au beams using a
      depth-sensing nanoindenter. It is found that the SiC film exhibits higher
      hardness, elastic modulus and scratch resistance as compared to other materials.
      In the bending tests, the nanoscale Si beams failed in a brittle manner with a
      flat fracture surface. The notched Ni-P beam showed linear deformation behavior
      followed by abrupt failure. The Au beam showed elastic-plastic deformation
      behavior. FEM simulation can well predict the stress distribution in the beams
      studied. The nanoindentation, scratch and bending tests used in this study can be
      satisfactorily used to evaluate the mechanical properties of micro/nanoscale
      structures for use in MEMS/NEMS.

PMID- 12801706
TI  - Finite element analysis of nanostructures with roughness and scratches.
AB  - Finite element analysis facilitates optimal design of MEMS/NEMS devices for
      reliability. A finite element method (FEM) was developed to analyze the effect of
      types of surface roughness and scratches on stresses of nanostructures. Beams
      with surface roughness in the form of semicircular and grooved asperities in
      varying numbers in the longitudinal direction were considered. In the transverse
      direction semicircular asperities and scratches in varying numbers and with
      different pitch were modeled. Furthermore semicircular asperities were truncated
      both in longitudinal and transverse direction and analyzed. It was observed that
      the asperities and scratches increase the bending tensile stresses which could
      lead to failure of MEMS/NEMS devices. The beam material was assumed to be purely
      elastic, elastic-plastic and elastic-perfectly plastic to observe the variations
      in the bending stresses and displacements for both smooth nanobeam and nanobeam
      with defined roughness. The results of the analysis can be useful to designers to
      develop the most suitable geometry for nanostructures.

PMID- 12801708
TI  - Some non-anomerically C-C-linked carbohydrate amino acids related to leucine
      synthesis and structure determination.
AB  - (5'R)-5'-Isobutyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4
      C-yl]-imidazolidin-2',4'-dione was synthesised starting from methyl 2,3-O
      isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside via methyl 6-deoxy-6
      isopropyl-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose applying the
      Bucherer-Bergs reaction. Its 5'-R configuration was confirmed by X-ray
      crystallography. Corresponding alpha-amino acid-methyl (5R)-5-amino-5-C-carboxy
      5,6-dideoxy-6-isopropyl-alpha-D-lyxo-hexofuranoside (alternative name: 2-[methyl
      (4R)-beta-L-erythrofuranosid-4-C-yl]-D-leucine) was obtained from the above
      hydantoin by acid hydrolysis of the isopropylidene group followed by basic
      hydrolysis of the hydantoin ring. Analogous derivatives with 5S configuration,
      formed in a minority, were also isolated and characterised.

PMID- 12801709
TI  - Synthesis and antitumor activity of new D-galactose-containing derivatives of
      doxorubicin.
AB  - A general scheme of synthesis of antibiotic doxorubicin derivatives is based on
      the 13-dimethyl ketal of 14-bromodaunorubicin (4). The interaction of 4 with
      melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D
      galactopyranosyl)-4-oxybenzaldehyde (12) or 4-O-(2,3,4,6-tetra-O-acetyl-beta-D
      galactopyranosyl)-4-oxybenzaldehyde (13) by reductive alkylation followed by
      hydrolysis of the corresponding intermediate bromoketals produced 3'-N-[alpha-D
      galactopyranosyl-(1-->6)-O-1-deoxy-D-glucit-1-yl]doxorubicin (7), 3'-N-[beta-D
      galactopyranosyl-(1-->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin (8), 3'-N-[3"
      methoxy-4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (16), and 3'-N
      [4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (17). Cytotoxic and
      antitumor activity of the synthesized drug candidates compared to the parent
      doxorubicin was studied using various experimental models, in particular, on mice
      bearing lymphocyte leukemia P-388 at single and multiple i.v. injection regimens.

PMID- 12801710
TI  - Synthesis of S-linked thiooligosaccharide analogues of Nod factors: synthesis of
      new protected thiodisaccharide and thiotrisaccharide intermediates.
AB  - We are investigating the synthesis of thioanalogues of nodulation factors that
      will be resistant to degradation by chitinases. To study the influence of our
      protecting group strategy, the glycosylation of 1,6-anhydro-2-azido-3-O-benzyl-2
      deoxy-beta-D-glucopyranoside (7) with two trichloroacetimidate glycosyl donors
      carrying an azido group at C-2 and either benzyl or benzoyl protecting groups on
      O-3 and O-4 was first attempted under catalysis with BF(3).Et(2)O in toluene.
      While glycosylation with the benzoylated glycosyl donor gave only a poor yield
      (27%) of the disaccharide, a similar reaction with the benzylated donor gave the
      corresponding disaccharide in good yield (77%). Although both products were
      obtained as anomeric mixtures, the benzylated donor led to improved
      stereoselectivity in favor of the desired beta-anomer (alpha:beta 3:7). Based on
      these results, a novel thiotrisaccharide was synthesized via the coupling of 7
      with 6-O-acetyl-4-S-(3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D
      glucopyranosyl)-2-azido-3-O-benzyl-2-deoxy-4-thio-alpha-D-glucopyranosyl
      trichloroacetimidate (25) also newly synthesized. After optimization of the
      reaction conditions, the desired thiotrisaccharide 4-O-[6-O-acetyl-4-S-(3,4,6-tri
      O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D-glucopyranosyl)-2-azido-3-O
      benzyl-2-deoxy-4-thio-beta-D-glucopyranosyl]-1,6-anhydro-2-azido-3-O-benzyl-2
      deoxy-beta-D-glucopyranoside (26beta) was obtained in 57% yield. These conditions
      led to an anomeric mixture in favor of the desired beta-anomer (alpha:beta 1:4.7)
      that was separated from the alpha-anomer by normal-phase HPLC on a PrepNova
      Pack(R) silica gel cartridge. The work described here shows that thiodisaccharide
      glycosyl donors behave quite differently from the analogous O-disaccharide used
      previously to synthesize nodulation factors.

PMID- 12801711
TI  - Characterizing the electrospray-ionization mass spectral fragmentation pattern of
      enzymatically derived hyaluronic acid oligomers.
AB  - Oligosaccharides derived from hyaluronic acid by action of bovine testicular
      hyaluronidase (BTH) (hyaluronate 4-glycanohydrolase, E.C. 3.2.1.35) were
      characterized by mass spectrometry (MS) with electrospray-ionization mass
      spectrometry (ESIMS) and compared with results obtained by matrix-assisted laser
      desorption/ionization. Both oligomers with an odd number and even number of sugar
      units with molecular masses up to 8 kDa were observed in the ESI spectra.
      However, the generation of odd-numbered oligomers is not consistent with the
      regiospecificity of the enzyme and with the MALDI results, which indicated even
      numbered oligomers exclusively. In addition, a third method of characterization,
      high-performance anion-exchange chromatography (HPAEC), showed only even-numbered
      oligomers. Relative intensities of the odd-numbered oligomers demonstrated in
      ESIMS a cone-voltage dependence suggesting the odd-numbered oligomers resulted
      from collisional activation. In order to achieve results by ESI that mirror
      results from other techniques, the cone voltage must be kept low and precisely
      controlled. This study displays the usefulness and possible vulnerabilities of
      ESIMS when utilized for carbohydrate analysis without corroborating data from
      other methods of analysis.

PMID- 12801712
TI  - Structure of the O-specific polysaccharide from the lipopolysaccharide of
      Citrobacter gillenii O11, strain PCM 1540.
AB  - The O-specific polysaccharide of the lipopolysaccharide of Citrobacter gillenii
      PCM 1540 (serogroup O11) consists of D-Glc, D-Man, D-GalNAc, D-GlcNAc, 2
      acetamido-2,6-dideoxy-D-galactose (D-FucNAc) and O-acetyl groups in the ratios
      2:1:1:1:1:1. On the basis of sugar and methylation analyses and Smith-degradation
      along with 1D and 2D 1H and 13C NMR spectroscopy, the following structure of the
      branched hexasaccharide repeating unit was established: [structure: see text].
      Citrobacter werkmanii PCM 1541 belonging to the same serogroup O11 was found to
      have an R-form lipopolysaccharide devoid of the O-specific polysaccharide.

PMID- 12801713
TI  - Synthesis of amylose acetates and amylose sulfates with high structural
      uniformity.
AB  - Amylose triacetate (ATA) dissolved in DMSO was partially deacetylated by 1,6
      hexamethylendiamine, 1,8-octamethylendiamine, 1,12-dodecylmethylendiamine and 1,2
      cyclohexyldiamine (mixture of cis and trans isomers) at 80 degrees C. The
      reaction kinetics of the deacetylation were studied. Differences were found in
      the course of the reaction depending on the type of alkylene diamine (linear or
      cyclic). The isolated amylose acetates were dissolved in DMF and subsequently
      sulfated with sulfamic acid. In the course of the sulfation, the acetyl groups
      acted as protective groups and were completely cleaved after reaction. The
      amylose acetates and sulfates obtained were studied by 13C NMR spectroscopy and
      elemental analysis. It could be shown, that the deacetylation of ATA with the
      described alkylene diamines as well as the subsequent sulfation are highly
      regioselective. By proceeding this reaction scheme it is possible to synthesize 6
      amyloseacetate, 2,6-di-amyloseacetate and 2-amylosesulfate with a high structural
      uniformity.

PMID- 12801714
TI  - Analysis of pyruvylated beta-carrageenan by 2D NMR spectroscopy and reductive
      partial hydrolysis.
AB  - A polysaccharide rich in 4',6'-O-(1-carboxyethylidene)-substituted (i.e.,
      pyruvylated) beta-carrageenan has been prepared by solvolytic desulfation of a
      polysaccharide containing predominantly pyruvylated alpha-carrageenan, which was
      extracted from the red seaweed, Callophycus tridentifer. The 13C and 1H NMR
      chemical shifts of pyruvylated beta-carrageenan have been fully assigned using 2D
      NMR spectroscopic techniques. The 4',6'-O-(1-methoxycarbonylethylidene) group,
      generated during chemical methylation of the polysaccharide, has been shown to
      survive under the conditions of acidic hydrolysis that cleave the 3,6-anhydro
      alpha-D-galactosidic bonds in permethylated samples of both pyruvylated beta- and
      pyruvylated alpha-carrageenans. As a result, two novel pyruvylated carrabiitol
      derivatives have been prepared.

PMID- 12801715
TI  - Activity coefficients of NaCl in trehalose-water and maltose-water mixtures at
      298.15 K.
AB  - The ionic mean activity coefficients of NaCl in trehalose-water and maltose-water
      mixtures have been experimentally determined at 298.15 K from emf measurements by
      electrochemical cell containing ion selective electrodes (ISE): Na-ISE/NaCl (m),
      sugar (Y%), H(2)O (100-Y%)/Cl-ISE. The electrolyte molality (m) ranged between
      0.01 and 3 mol kg(-1), approximately, and the weight percent (Y%) of sugar in the
      mixture of solvents between 0, 10, 20, 30 and 40%. The system is considered as an
      electrolyte in a mixture of solvents and the data have been analysed by using the
      Debye-Huckel and Pitzer equations. The results obtained with both equations are
      in quite agreement with each other. The variation of the fit parameter from both
      equations were studied relative to the change in the dielectric properties of the
      mixture of solvents. Standard free energy of transference were comparatively
      discussed in terms of ion-solvent, ion-ion interactions and the hydration of both
      the electrolyte and the sugar.

PMID- 12801716
TI  - Structure of the O-polysaccharide of Providencia alcalifaciens O21 containing 3
      formamido-3,6-dideoxy-D-galactose.
AB  - The O-polysaccharide (O-antigen) of Providencia alcalifaciens O21 was obtained by
      mild acid degradation of the lipopolysaccharide and studied by chemical methods
      and NMR spectroscopy. It was found that the polysaccharide is built up of
      branched pentasaccharide repeating units with a terminal residue of 3-formamido
      3,6-dideoxy-D-galactose (D-Fuc3NFo) and has the following structure: [structure:
      see text]. Anti-P. alcalifaciens O21 serum cross-reacted with the O-antigen of
      Proteus vulgaris O47, which contains a GalNAc trisaccharide similar to that
      present in the P. alcalifaciens O21 O-polysaccharide.

PMID- 12801717
TI  - Structure of the O-polysaccharide of Proteus vulgaris O44: a new O-antigen that
      contains an amide of D-glucuronic acid with L-alanine.
AB  - The O-polysaccharide of Proteus vulgaris O44, strain PrK 67/57 was studied by 1H
      and 13C NMR spectroscopy, including 2D COSY, TOCSY, ROESY, H-detected 1H, 13C
      HMQC, HMQC-TOCSY and HMBC experiments. The polysaccharide was found to contain an
      amide of D-glucuronic acid with L-alanine [D-GlcA6(L-Ala)], and the following
      structure of the linear pentasaccharide repeating unit was established:
      [structure: see text]. The structural data of the O-polysaccharide and the
      results of serological studies with P. vulgaris O44 O-antiserum showed that the
      strain studied is unique among Proteus bacteria, which is in agreement with its
      classification in a separate Proteus serogroup, O44.

PMID- 12801718
TI  - Splicing goes global.
AB  - Transcriptomics, the analysis of the complement of mRNAs transcribed from a
      cell's genome, currently focuses mainly on mature, processed mRNAs. However,
      posttranscriptional processing of primary transcripts can significantly affect
      both the quantity and the structure of the mature mRNAs and therefore of the
      protein products. Recently, the development of an intron-specific microarray has
      permitted a preliminary analysis of the splicing of all intron-containing
      transcripts in Saccharomyces cerevisiae. Here, we discuss the findings and what
      might be learned from this kind of approach.

PMID- 12801719
TI  - Transcription and the territory: the ins and outs of gene positioning.
AB  - When cells exit mitosis, the neat rod-like chromosomes decondense into their
      interphase state. However, the chromatin threads are not randomly dispersed
      throughout the nucleoplasm. Rather, individual chromosomes appear to be organized
      into discrete, non-overlapping "territories". Current studies attempt to unravel
      how gene loci are organized within these territories, whether their
      subterritorial positions are dependent on transcription, and the extent to which
      the loci can move.

PMID- 12801720
TI  - Quantitative traits in plants: beyond the QTL.
AB  - Phenotypic variation for quantitative traits results from segregation at multiple
      quantitative trait loci (QTL), the effects of which are modified by the internal
      and external environments. Because of their favorable genetic attributes (e.g.
      short generation time, large families and tolerance to inbreeding), plants are
      often used to test new concepts in quantitative trait analysis. Thus far, the
      molecular basis underlying allelic variation at QTL is similar to the identified
      variation for simple mendelian loci; namely, alterations in gene expression or
      protein function. Further comprehensive dissection of complex phenotypes will
      depend on our ability to link genetic components of the QTL variation to genomic
      databases.

PMID- 12801721
TI  - An evolutionary approach reveals a high protein-coding capacity of the human
      genome.
AB  - We developed a new evolutionary method for identifying exons from genomic
      sequences and found 19000 potential coding exons that are absent from all
      existing annotations of the human genome. Of these, 13700 satisfied very
      stringent criteria and can with confidence be considered as novel exons.
      Evidently, a large number of new human genes can be identified using evolutionary
      approaches.

PMID- 12801722
TI  - FlyMove--a new way to look at development of Drosophila.
AB  - Development of any organism requires a complex interplay of genes to orchestrate
      the many movements needed to build up an embryo. Previously, work on Drosophila
      melanogaster has provided important insights that are often applicable in other
      systems. But developmental processes, which take place in space and time, are
      difficult to convey in textbooks. Here, we introduce FlyMove (http://flymove.uni
      muenster.de), a new database combining movies, animated schemata, interactive
      "modules" and pictures that will greatly facilitate the understanding of
      Drosophila development.

PMID- 12801723
TI  - BRCA1: the enigma of tissue-specific tumor development.
AB  - Recent evidence indicates that BRCA1, a gene product associated with breast and
      ovarian cancer susceptibility, is an important component of the cellular response
      to DNA damage. Despite being expressed ubiquitously in adult tissues, germline
      mutations in BRCA1 predispose individuals to breast and ovarian tumors with only
      minor effects on the predisposition to cancer in other sites. The reason for this
      tissue specificity of BRCA1 carcinomas must be found if we are to understand
      fully why these tumors occur and to enable us to design efficient preventive and
      therapeutic regimens. Here I propose that tissue-specific rates of loss of
      heterozygosity in the BRCA1 locus could contribute to tissue specificity in tumor
      development.

PMID- 12801724
TI  - Nonsyndromic X-linked mental retardation: where are the missing mutations?
AB  - Analysis of linkage intervals from 125 unrelated families with nonsyndromic X
      linked mental retardation (NS-XLMR) has revealed that the respective gene defects
      are conspicuously clustered in defined regions of the human X-chromosome, with
      approximately 30% of all mutations being located on the proximal Xp. In 83% of
      these families, underlying gene defects are not yet known. Our observations
      should speed up the search for mutations that are still missing and pave the way
      for the molecular diagnosis of this common disorder.

PMID- 12801725
TI  - The diverse functions of histone acetyltransferase complexes.
AB  - Although histone acetylation has historically been linked to transcription
      activation, recent studies indicate that this modification and the enzymes that
      catalyze it have much broader and diverse functions. Histone acetyltransferase
      complexes are involved in such diverse processes as transcription activation,
      gene silencing, DNA repair and cell-cycle progression. The high conservation of
      the acetyltransferase complexes and their functions illustrates their central
      role in cell growth and development.

PMID- 12801726
TI  - Biased gene conversion: implications for genome and sex evolution.
AB  - Classical genetic studies show that gene conversion can favour some alleles over
      others. Molecular experiments suggest that gene conversion could favour GC over
      AT basepairs, leading to the concept of biased gene conversion towards GC
      (BGC(GC)). The expected consequence of such a process is the GC-enrichment of DNA
      sequences under gene conversion. Recent genomic work suggests that BGC(GC)
      affects the base composition of yeast, invertebrate and mammalian genomes.
      Hypotheses for the mechanisms and evolutionary origin of such a strange
      phenomenon have been proposed. Most BGC(GC) events probably occur during meiosis,
      which has implications for our understanding of the evolution of sex and
      recombination.

PMID- 12801727
TI  - Fox's in development and disease.
AB  - Since the first forkhead (Fox) gene was identified, the importance of this family
      of transcription factors has increased steadily with the discoveries of the
      diverse range of developmental processes that they regulate in eukaryotes. Among
      other processes, the Fox factors are important in the establishment of the body
      axis and the development of tissues from all three germ layers. In this article,
      we present some of the recent data on this gene family with reference to selected
      phenotypes observed in patients and model organisms, and the sensitivity of
      developmental processes to alterations in forkhead gene dosage.

PMID- 12801728
TI  - Phylogeny for the faint of heart: a tutorial.
AB  - Phylogenetic trees seem to be finding ever broader applications, and researchers
      from very different backgrounds are becoming interested in what they might have
      to say. This tutorial aims to introduce the basics of building and interpreting
      phylogenetic trees. It is intended for those wanting to understand better what
      they are looking at when they look at someone else's trees or to begin learning
      how to build their own. Topics covered include: how to read a tree, assembling a
      dataset, multiple sequence alignment (how it works and when it does not),
      phylogenetic methods, bootstrap analysis and long-branch artefacts, and software
      and resources.

PMID- 12801729
TI  - Who will take responsibility for corporate killing?

PMID- 12801730
TI  - Perioperative chemotherapy in locally advanced bladder cancer.

PMID- 12801731
TI  - Cholinergic denervation in diverticular disease.

PMID- 12801732
TI  - Brain and mind: a challenge for WHO.

PMID- 12801733
TI  - Age and the treatment gap in the use of statins.

PMID- 12801734
TI  - Appealing to editors?

PMID- 12801735
TI  - Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: Controversy exists as to whether neoadjuvant chemotherapy improves
      survival in patients with invasive bladder cancer, despite randomised controlled
      trials of more than 3000 patients. We undertook a systematic review and meta
      analysis to assess the effect of such treatment on survival in patients with this
      disease. METHODS: We analysed updated data for 2688 individual patients from ten
      available randomised trials. FINDINGS: Platinum-based combination chemotherapy
      showed a significant benefit to overall survival (combined hazard ratio [HR] 0.87
      [95% CI 0.78-0.98, p=0.016]; 13% reduction in risk of death; 5% absolute benefit
      at 5 years [1-7]; overall survival increased from 45% to 50%). This effect was
      observed irrespective of the type of local treatment, and did not vary between
      subgroups of patients. The HR for all trials, including those using single-agent
      cisplatin, tended to favour neoadjuvant chemotherapy (HR=0.91, 95% CI 0.83-1.01)
      although this tendency was not significant (p=0.084). Although platinum based
      combination chemotherapy was beneficial, there was no evidence to support the use
      of single-agent platinum; indeed, there was a significant difference in the
      effect between these groups of trials (p=0.044). INTERPRETATION: This improvement
      in survival encourages the use of platinum-based combination chemotherapy for
      patients with invasive bladder cancer.

PMID- 12801736
TI  - Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a
      single-blind, randomised, placebo-controlled trial.
AB  - BACKGROUND: Deliberate self-poisoning with yellow oleander seeds is common in Sri
      Lanka and is associated with severe cardiac toxicity and a mortality rate of
      about 10%. Specialised treatment with antidigoxin Fab fragments and temporary
      cardiac pacing is expensive and not widely available. Multiple-dose activated
      charcoal binds cardiac glycosides in the gut lumen and promotes their
      elimination. We aimed to assess the efficacy of multiple-dose activated charcoal
      in the treatment of patients with yellow-oleander poisoning. METHODS: On
      admission, participants received one dose of activated charcoal and were then
      randomly assigned either 50 g of activated charcoal every 6 h for 3 days or
      sterile water as placebo. A standard treatment protocol was used in all patients.
      We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death
      was the primary endpoint, and secondary endpoints were life-threatening cardiac
      arrhythmias, dose of atropine used, need for cardiac pacing, admission to
      intensive care, and number of days in hospital. Analysis was by intention to
      treat. FINDINGS: 201 patients received multiple-dose activated charcoal and 200
      placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%];
      percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in
      favour of the treatment group for all secondary endpoints, apart from number of
      days in hospital. The drug was safe and well tolerated. INTERPRETATION: Multiple
      dose activated charcoal is effective in reducing deaths and life-threatening
      cardiac arrhythmias after yellow oleander poisoning and should be considered in
      all patients. Use of activated charcoal could reduce the cost of treatment.

PMID- 12801737
TI  - Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced
      asthma in children.
AB  - BACKGROUND: A link between exposure to the air pollutant nitrogen dioxide (NO2)
      and respiratory disease has been suggested. Viral infections are the major cause
      of asthma exacerbations. We aimed to assess whether there is a relation between
      NO2 exposure and the severity of asthma exacerbations caused by proven
      respiratory viral infections in children. METHODS: A cohort of 114 asthmatic
      children aged between 8 and 11 years recorded daily upper and lower respiratory
      tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures
      every week for up to 13 months. We took nasal aspirates during reported episodes
      of upper respiratory-tract illness and tested for infection by common respiratory
      viruses and atypical bacteria with RT-PCR assays. We used generalised estimating
      equations to assess the relation between low (<7.5 microg/m3), medium (7.5-14
      microg/m3 ), and high (>14 microg/m3) tertiles of NO2 exposure in the week before
      or after upper respiratory-tract infection and the severity of asthma
      exacerbation in the week after the start of an infection. FINDINGS: One or more
      viruses were detected in 78% of reported infection episodes, and the medians of
      NO2 exposure were 5 (IQR 3.6-6.3), 10 (8.7-12.0), and 21 microg/m3 (16.8-42.9)
      for low, medium, and high tertiles, respectively. There were significant
      increases in the severity of lower respiratory-tract symptom scores across the
      three tertiles (0.6 for all viruses [p=0.05] and >2 for respiratory syncytial
      virus [p=0.01]) and a reduction in PEF of more than 12 L/min for picornavirus
      (p=0.04) for high compared with low NO2 exposure before the start of the virus
      induced exacerbation. INTERPRETATION: High exposure to NO2 in the week before the
      start of a respiratory viral infection, and at levels within current air quality
      standards, is associated with an increase in the severity of a resulting asthma
      exacerbation.

PMID- 12801738
TI  - Smooth muscle cholinergic denervation hypersensitivity in diverticular disease.
AB  - BACKGROUND: Evidence from clinical and laboratory investigations into the causes
      of diverticular disease suggests that disturbances in cholinergic activity are
      important, the effector mechanisms of which have yet to be established. We aimed
      to investigate the role of smooth muscle and neural cholinergic activity in the
      pathogenesis of this disease. METHODS: Two investigators independently did a
      blinded immunohistochemical image analysis of localising antibodies to choline
      acetyltransferase, co-localised with protein gene product (PGP)--a marker of
      general neural tissue-and smooth muscle muscarinic M3 receptors, on three
      histological sections of sigmoid colons from ten patients with diverticular
      disease and ten controls, after resections for rectal tumours. We also did
      isotonic organ bath experiments to assess muscle strip sensitivities to exogenous
      acetylcholine. FINDINGS: In circular muscle, activity of choline
      acetyltransferase was lower in patients with diverticular disease than in
      controls: median percentage surface area of choline acetyltransferase over PGP
      was 17.5% (range 10.0-37.0) in patients with diverticular disease and 47.0% (29.0
      54.0) in controls (p<0.0001). M3 receptors were upregulated in patients with
      diverticular disease compared with controls: the median surface area was 13.2%
      (6.0-23.3) in patients with diverticular disease and 2.5% (1.6-3.7) in controls
      (p<0.0001). The sensitivity to exogenous acetylcholine was increased in patients
      with diverticular disease (mean -log EC(50) 5.6 [SD 0.3]) compared with controls
      (4.9 [0.5]; difference 0.7 [95% CI 0.3-1.1], p=0.006). In longitudinal muscle,
      choline acetyltransferase activity was lower in patients with diverticular
      disease (median 19.5%, range 12.0-30.0) than in controls (47.0%, 35.0-60.0;
      p<0.0001), with upregulation of M3 receptors in diverticular disease
      (diverticular disease 7.8% [1.9-20.4], controls 1.7% [0.8-3.0]; p<0.0001).
      However, sensitivity to exogenous acetylcholine did not differ between the two
      groups (diverticular disease mean 5.6% [SD 0.3], controls 5.2% [0.4]; difference
      0.4% [95% CI -0.02-0.7], p=0.06). INTERPRETATION: Our results suggest that
      cholinergic denervation hypersensitivity can affect smooth muscle. Upregulation
      of smooth muscle M3 receptors might account for specific clinical, physiological,
      and pharmacological abnormalities associated with diverticular disease.

PMID- 12801739
TI  - A warble in Connecticut.

PMID- 12801740
TI  - Estimated early-onset group B streptococcal neonatal disease.
AB  - Estimates of incidence of early-onset group B streptococcal (EOGBS) infection are
      based on blood or cerebrospinal fluid culture-proven cases, which can be falsely
      negative and hence underestimate the true burden of disease. Probable EOGBS
      infection can be defined as colonisation by group B streptococci accompanied by
      features of clinical sepsis. Data collected prospectively in the UK over 1 year
      for neonates who required a septic screen in the first 72 h of life indicated a
      combined rate of definite and probable EOGBS infection of 3.6 per 1000
      livebirths. This estimate indicates a much greater disease burden in the UK than
      that suggested by figures of culture-proven sepsis, and lends support to the need
      for prevention strategies.

PMID- 12801741
TI  - Gynaecomastia in men with chronic myeloid leukaemia after imatinib.
AB  - cKit and platelet-derived growth-factor receptor (PDGFR) are receptor tyrosine
      kinases expressed in the testis, are involved in testosterone production, and are
      inhibited by imatinib. We measured hormone concentrations in 38 men receiving
      imatinib for chronic myeloid leukaemia at baseline and during treatment. Mean
      follow-up was 23.6 months (SD 7.5). We noted seven cases of gynaecomastia (18%,
      95% CI 6-30%). A comparison of hormone concentrations in 21 patients before and
      during treatment showed that patients who developed gynaecomastia had a reduction
      in free testosterone concentrations of 29.53 pmol/L (95% CI 11.63-47.43), while
      patients who did not had a decrease of 6.36 pmol/L (-1.02 to 13.74). In most men
      with chronic myeloid leukaemia studied here, imatinib was associated with a
      reduction in the production of testicular hormones and in some, with the
      development of gynaecomastia.

PMID- 12801742
TI  - Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Abeta to
      physiologically relevant proteolytic degradation.
AB  - The Dutch, Flemish, Italian, and Arctic mutations in the amyloid precursor
      protein (APP) gene encode changes within the sequence of the amyloid beta peptide
      (Abeta) and cause presenile cerebral amyloid angiopathy, cerebral parenchymal
      amyloidosis, or both. These disorders are caused by accumulation of Abeta, with
      no evidence of increased Abeta production. Our results showed that these
      mutations in Abeta make it resistant to proteolytic degradation by neprilysin,
      the peptidase with the most important role in catabolism of Abeta in the brain.
      These mutations in Abeta could thus be pathogenic not only by facilitating
      fibrillogenesis but also by extending the half-life of Abeta in the brain.

PMID- 12801743
TI  - Antiangiogenesis drug promising for metastatic colorectal cancer.

PMID- 12801744
TI  - Labour presses on with health service reforms.

PMID- 12801745
TI  - Global security takes priority over health at G8 summit.

PMID- 12801746
TI  - Enlarged European Union aims for healthy citizens.

PMID- 12801751
TI  - Reproductive health struggles in Nigeria.

PMID- 12801752
TI  - High-altitude illness.
AB  - High-altitude illness is the collective term for acute mountain sickness (AMS),
      high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE).
      The pathophysiology of these syndromes is not completely understood, although
      studies have substantially contributed to the current understanding of several
      areas. These areas include the role and potential mechanisms of brain swelling in
      AMS and HACE, mechanisms accounting for exaggerated pulmonary hypertension in
      HAPE, and the role of inflammation and alveolar-fluid clearance in HAPE. Only
      limited information is available about the genetic basis of high-altitude
      illness, and no clear associations between gene polymorphisms and susceptibility
      have been discovered. Gradual ascent will always be the best strategy for
      preventing high-altitude illness, although chemoprophylaxis may be useful in some
      situations. Despite investigation of other agents, acetazolamide remains the
      preferred drug for preventing AMS. The next few years are likely to see many
      advances in the understanding of the causes and management of high-altitude
      illness.

PMID- 12801753
TI  - Rare congenital disorders, imprinted genes, and assisted reproductive technology.
AB  - CONTEXT: During the past two decades, assisted reproductive technologies (ARTs)
      have revolutionised the treatment of infertility. ARTs now account for between 1%
      and 3% of annual births in many western countries and in-vitro fertilisation
      (IVF) services are growing worldwide. In general, the incidence of abnormalities
      at birth is reassuringly low and children develop normally. Nevertheless, it is
      important to monitor the safety of ARTs as clinical protocols evolve and new
      technologies emerge. STARTING POINT: Three recent studies all report an
      unexpectedly high incidence of Beckwith-Wiedemann syndrome (BWS) in children
      conceived with ARTs. Six of 149 cases were reported from a British BWS registry
      (J Med Genet 2003; 40: 62-64); the same numbers were recorded in a French
      registry (Am J Hum Genet 2003; 72: 1338-41), and a further seven children have
      been reported in the USA (Am J Hum Genet 2003; 72: 156-60). These frequencies are
      extraordinarily high for such a rare congenital condition and such findings are
      reminiscent of reports of sporadic cases of the imprinting disorder, Angelman
      syndrome, which has also been linked with ARTs. WHERE NEXT? Continuing
      surveillance of children conceived with ARTs is needed, including monitoring
      birth defects, development, and cancer. Studies will need to be prospective and
      multicentre, and should include molecular characterisation of epigenetic
      abnormalities, including the methylation status of imprinting control regions
      within imprinted gene clusters.

PMID- 12801754
TI  - Improving the performance of health services: the role of clinical leadership.

PMID- 12801755
TI  - Public health and the human rights of sex workers.

PMID- 12801756
TI  - Can health programmes lead to mistreatment of sex workers?

PMID- 12801757
TI  - Confusion between prostitution and sex trafficking.

PMID- 12801758
TI  - Personal view of SARS: confusing definition, confusing diagnoses.

PMID- 12801759
TI  - Lymphopenia in SARS.

PMID- 12801760
TI  - ASCOT-LLA: questions about the benefits of atorvastatin.

PMID- 12801761
TI  - ASCOT-LLA: questions about the benefits of atorvastatin.

PMID- 12801762
TI  - ASCOT-LLA: questions about the benefits of atorvastatin.

PMID- 12801764
TI  - ASCOT-LLA: questions about the benefits of atorvastatin.

PMID- 12801765
TI  - ASCOT-LLA: questions about the benefits of atorvastatin.

PMID- 12801766
TI  - Lipoproteins and cardiovascular risk.

PMID- 12801767
TI  - Lipoproteins and cardiovascular risk.

PMID- 12801769
TI  - McFarlane's law, critical mass, and clinical research.

PMID- 12801770
TI  - Selection bias introduced by the informed consent process.

PMID- 12801771
TI  - Selection bias introduced by the informed consent process.

PMID- 12801772
TI  - Disabling cough: habit disorder or tic syndrome?

PMID- 12801773
TI  - Disabling cough: habit disorder or tic syndrome?

PMID- 12801775
TI  - Clinical efficacy and toxicity of gefitinib in patients with lung cancer.

PMID- 12801776
TI  - Clinical efficacy and toxiciy of gefitinib in patients with lung cancer.

PMID- 12801777
TI  - Human telomerase RNA mutations and bone marrow failure.

PMID- 12801779
TI  - The death of Lord Carnarvon.

PMID- 12801780
TI  - Just-in-time lectures: SARS.

PMID- 12801783
TI  - The right to quackery.

PMID- 12801785
TI  - Sample collection for DNA analysis: divining nature's answers or discreetly
      nurturing advantage?

PMID- 12801786
TI  - New approach to gene expression analysis.

PMID- 12801787
TI  - Spinach makes a safer anthrax vaccine.

PMID- 12801788
TI  - Drug reactivates genes to inhibit cancer.

PMID- 12801791
TI  - Leroy Hood expounds the principles, practice and future of systems biology.

PMID- 12801792
TI  - Trust me--I'm a doctor!

PMID- 12801793
TI  - Targeting structured nucleic acids with antisense agents.

PMID- 12801794
TI  - Tumor markers: discovery to practice.

PMID- 12801796
TI  - GABA-A receptor subtypes in the brain: a paradigm for CNS drug discovery?
AB  - The clinical importance of benzodiazepines, barbiturates and general anesthetics,
      all of which act through the gamma-aminobutyric acid (GABA)-A neurotransmitter
      receptor, is testament to its significance as a CNS drug target. These drugs were
      all developed before there was any understanding of the diversity of this
      receptor gene family. Recent studies using genetically modified mice and GABA-A
      receptor-subtype-selective compounds have helped to delineate the function of
      some of these subtypes, and have revealed that it might be possible to develop a
      new generation of selective drugs with improved profiles or novel applications.

PMID- 12801797
TI  - Quantitative image analysis: software systems in drug development trials.
AB  - Multi-dimensional image analysis is being used increasingly to arrive at
      surrogate end-points for drug development trials. Various imaging modalities such
      as computed tomography (CT), magnetic resonance imaging (MRI), positron emission
      tomography (PET) and ultrasound are used to analyze treatments for diseases such
      as cancer, multiple sclerosis, osteoarthritis, and Alzheimer's disease. However,
      extracting information from images can be tedious and is prone to high user
      variability. The medical image analysis community is moving towards advanced
      software systems specifically designed for drug development trials. These systems
      can automatically identify the anatomy of interest in medical images
      (segmentation methods), can compare the anatomy over time or between patients
      (registration methods) and allow the quantitative extraction of anatomical
      features and the integration of the data and results into a database management
      system, automatically tracking the changes made to the data (audit trail
      generation). In this article, we present a case study using a prototype system
      that is used for quantifying multiple sclerosis lesions from multivariate MRI.

PMID- 12801798
TI  - Reverse vaccinology.
AB  - Whole-genome sequencing of bacteria and advances in bioinformatics have
      revolutionized the vaccinology field, leading to the identification of potential
      vaccine candidates without the need for cultivating the pathogen. This approach,
      termed "reverse vaccinology", reduces the time and cost required for the
      identification of candidate vaccines and provides new solutions for those
      diseases for which conventional approaches have failed. The first example of the
      potential of reverse vaccinology has been the identification of novel antigens of
      meningococcus B as potential candidates for a novel and effective vaccine. The
      same approach has been successfully applied to other important human pathogens,
      demonstrating the feasibility to develop vaccines against any infectious disease.
      This review focuses on some recent advances in the identification of vaccine
      candidates by mining the genomic sequences of pathogenic bacteria.

PMID- 12801800
TI  - The control of immunity and tolerance by dendritic cell.
AB  - Dendritic cells (DCs) are best known for their roles in host resistance and
      immunogenicity. DCs provide a direct link between innate and adaptive immunity.
      After antigen capture and processing, DCs control the differentiation and
      polarization of T cells. However, there is a danger during the antigen
      presentation because, at the same time DCs are capturing microbial antigens and
      also dying self cells and environmental proteins, to which the immune system must
      not respond. There is good evidence that immature DCs, in the absence of
      infection and inflammation, induce immunological tolerance to innocuous self
      antigens, avoiding then a non-appropriate response to harmless antigens that may
      be presented subsequently when infection strikes.

PMID- 12801801
TI  - Molecular characterization of dendritic cells operating at the interface of
      innate or acquired immunity.
AB  - Dendritic Cells (DC) are natural adjuvants able to elicit specific cellular
      interactions and priming of naive T cells at a mature stage of their
      differentiation. Recent genomic approaches helped defining DC or Langherans Cells
      (LC) in more molecular terms. DC-SIGN, the DC specific ICAM-3 grabbing non
      integrin is a C-type lectin, absent on LC but expressed on dermal, lymph node and
      tonsils DC. DC-SIGN is defined as an ICAM-3 receptor supporting DC mediated-T
      cell proliferation. Moreover, DC-SIGN plays an important role in binding and
      presentation of HIV virions, because DC-SIGN specifically binds the gp120 coat
      protein of HIV.DC-SIGN also plays a part in DC trafficking since it not only
      binds ICAM-3 but also ICAM-2 expressed by many endothelial cells, supporting
      tethering and rolling of DC on endothelium and chemokine induced-transmigration
      of DC across both resting and activated endothelium in vitro. ALCAM (Activated
      Leukocyte Cell Adhesion Molecule) is another cell surface protein expressed by DC
      upon differentiation from monocytes. ALCAM appears to be expressed on activated
      leukocytes and might be involved in inflammatory processes. ALCAM belongs to the
      IgG superfamily of proteins and mediate heterotypic (T cell antigen ligand CD6)
      or homotypic interactions. ALCAM is linked to the cytoskeleton and might play a
      role in DC migration. Measurements of cell/cell contacts at single molecular
      levels using optical traps is a useful tool to investigate intercellular
      interactions.

PMID- 12801802
TI  - Cytokine-driven proliferation and differentiation of human naive, central memory
      and effector memory CD4+ T cells.
AB  - Memory T lymphocytes divide in vivo in the absence of antigen maintaining a pool
      of central memory (T(CM)) and effector memory cells (T(EM)) with distinct
      effector function and homing capacity. We compared human CD4+ naive T, T(CM) and
      T(EM) cells for their capacity to proliferate in response to cytokines, which
      have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded
      with very high efficiency T(EM), while T(CM) were less responsive and naive T
      cells did not respond at all. Dendritic cell (DC)-derived cytokines allowed naive
      T cells to respond selectively to IL-4 and potently boosted the response of T(CM)
      to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rss and the
      common gamma chain (gamma(c)). The ERK and the p38 MAP kinases were selectively
      required for TCR and cytokine-driven proliferation, respectively. Importantly, in
      cytokine-driven cultures T(CM) proliferated and some of the proliferating cells
      acquired effector function and non-lymphoid tissue homing capacity. Ex vivo BrdU
      incorporation experiments showed that both T(CM) and T(EM) proliferated under
      steady state conditions in vivo. Altogether these results provide a plausible
      mechanism for the maintenance of a polyclonal and functionally diverse repertoire
      of human CD4+ memory T cells and for a sustained antigen-independent generation
      of T(EM) from a pool of T(CM) cells.

PMID- 12801803
TI  - Regulation of dendritic cell function by microbial stimuli.
AB  - Dendritic cells (DC) initiate T cell responses and produce cytokines and other
      molecules that can regulate the class adaptive immunity. It is increasingly clear
      that DC in vivo are in a "resting" state and require exogenous signals to transit
      into an "effector" state in which they can prime T cells. Much of this DC
      activation process appears to be regulated by infection. Exposure of murine DC to
      certain pathogens or their products triggers DC migration to T cell areas of
      secondary lymphoid tissues, improves MHC presentation and increases DC co
      stimulatory potential. Pathogen recognition can also initiate cytokine production
      and/or condition DC to produce cytokines in response to subsequent T cell
      feedback signals delivered via CD40 and similar receptors. Recognition of
      pathogens by DC is largely dependent on Toll-like receptors (TLRs).
      Interestingly, mouse splenic CD8alpha+ and CDalpha-CD4- DC have the ability to
      produce either IL-12 p70 or IL-10 depending on the nature of the pathogen
      encountered. In contrast, CD4+ DC seem incapable of producing IL-12 p70. Thus,
      the nature of the pathogen can dictate the type of cytokine that is made by some
      DC subsets, allowing them to prime distinct types of immune responses. Overall,
      DC display significant plasticity in their ability to respond to infection and
      direct adaptive immunity.

PMID- 12801804
TI  - Identification of a new mechanism for bacterial uptake at mucosal surfaces, which
      is mediated by dendritic cells.
AB  - Dendritic cells are potent activators of the immune response. They reside in
      tissues which interface the external environment, but we shall see that they do
      not perform only a passive role by monitoring microorganisms that have entered
      the body. Rather, DC can actively participate to microbial entry across mucosal
      surfaces by creeping between epithelial cells and by internalizing bacteria via
      their dendrites.

PMID- 12801805
TI  - The use of the murine model of infection with Leishmania major to reveal the
      antagonistic effects that IL-4 can exert on T helper cell development and
      demonstrate that these opposite effects depend upon the nature of the cells
      targeted for IL-4 signaling.
AB  - In contrast to mice from the majority of inbred strains, BALB mice develop
      aberrant Th2 responses and suffer progressive disease after infection with
      Leishmania major. These outcomes depend on the production of Interleukin 4,
      during the first 2 d of infection, by CD4+ T cells that express the Vbeta4
      Valpha8 T cell receptors specific for a dominant I-A(d) restricted epitope of the
      LACK antigen from L. major. In contrast to this well established role of IL-4 in
      Th2 cell maturation, we have recently shown that, when limited to the initial
      period of activation of dendritic cells by L. major preceding T cell priming, IL
      4 directs DCs to produce IL-12, promotes Th1 cell maturation and resistance to L.
      major in otherwise susceptible BALB/c mice. Thus, the antagonistic effects that
      IL-4 can have on Th cell development depend upon the nature of the cells (DCs or
      primed T cells) targeted for IL-4 signaling.

PMID- 12801806
TI  - [Immunotherapy based on dendritic cells: from experimentation to clinical
      development].
AB  - Although the DC-based immunotherapy of cancer has been promising in animal
      models, several questions need to be addressed in depth in humans: the generation
      of various types of dendritic cells, the analysis of their potential and the
      immunomonitoring of cancer patients. In our laboratory, our efforts have been
      focused on (i) the study of the cytotoxic activity of dendritic cells; (ii) the
      generation of a novel population of human dendritic cells from monocytes cultured
      in IL-3 and IFN-beta; (iii) the optimisation of the immunostimulatory properties
      of DC using Fas-ligand surexpression or adjuvants promoting DC/gamma-delta T cell
      interaction.

PMID- 12801807
TI  - [Proceedings and abstracts from the Congress of the Francophone Club of Dendritic
      cells, 2001].

PMID- 12801808
TI  - [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular
      disease?. 1. Basic data].
AB  - Recent epidemiological studies have suggested that hyperhomocysteinemia is
      associated with increased risk of vascular disease. Homocysteine is a sulphur
      containing amino acid whose metabolism stands at the intersection of two
      pathways: remethylation to methionine, which requires folate and vitamin B12 (or
      betaine in an alternative reaction); and transsulfuration to cystathionine which
      requires vitamin B6. The two pathways are coordinated by S-adenosylmethionine
      which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase
      (MTHFR) and as an activator of cystathionine beta-synthase (CBS).
      Hyperhomocysteinemia arises from disrupted homocysteine metabolism. Severe
      hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in
      CBS, MTHFR, or in enzymes involved in methyl cobalamine synthesis and
      homocysteine methylation. Mild hyperhomocysteinemia seen in fasting condition is
      due to mild impairment in the methylation pathway (i.e. folate or B12
      deficiencies or MTHFR thermolability). Post-methionine-load hyperhomocysteinaemia
      may be due to heterozygous cystathionine-beta-synthase defect or B6 deficiency.
      Patients with homocystinuria and severe hyperhomocysteinemia develop arterial
      thrombotic events, venous thromboembolism, and more seldom premature
      arteriosclerosis. Experimental evidence suggests that an increased concentration
      of homocysteine may result in vascular changes through several mechanisms. High
      levels of homocysteine induce sustained injury of arterial endothelial cells,
      proliferation of arterial smooth muscle cells and enhance expression/activity of
      key participants in vascular inflammation, atherogenesis, and vulnerability of
      the established atherosclerotic plaque. These effects are supposed to be mediated
      through its oxidation and the concomitant production of reactive oxygen species.
      Other effects of homocysteine include: impaired generation and decreased
      bioavailability of endothelium-derived relaxing factor/nitric oxide; interference
      with many transcription factors and signal transduction; oxidation of low-density
      lipoproteins; lowering of endothelium-dependent vasodilatation. In fact, the
      effect of elevated homocysteine appears multifactorial affecting both the
      vascular wall structure and the blood coagulation system.

PMID- 12801810
TI  - [The double helix: 50 years and always with it! A small step for a helix, a giant
      step for science].

PMID- 12801809
TI  - [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular
      disease? 2. Epidemiological data].
AB  - Elevated plasma total homocysteine (tHcy) is considered as a risk factor for
      occlusive cardiovascular disease (CVD). This concept is based on the observations
      of premature vascular disease in patients with homocystinuria and on the
      association between tHcy and increased risk of CVD in prospective studies.
      However, some observations have raised questions about tHcy as a risk factor.
      First, low risk population based prospective studies tend to indicate a weak
      association or no association between tHcy and CVD. Second, several traditional
      risk factors for CVD are associated with tHcy and may confound the relation
      between tHcy and CVD. Third, the C667T transition of the
      methylenetetrahydrofolate reductase causes a moderate increase in tHcy but no or
      only minor increased CVD risk. Thus, only placebo-controlled intervention studies
      with tHcy-lowering B-vitamins and clinical endpoints can provide additional valid
      arguments for the debate over whether tHcy is a causal CVD risk factor.

PMID- 12801811
TI  - [Extemporaneous histologic examination in infraclinical mammary lesions].

PMID- 12801812
TI  - [Hommage to Professor Claude Helene].

PMID- 12801813
TI  - [G-quadruplex DNA: myth or reality?].
AB  - The peculiar sequence of telomeric DNA, composed of repetitions of the GGTTAG
      motif allows the formation of an unusual DNA conformation based on guanine
      quadruplex (G-quadruplex). Small molecules that bind and stabilize telomeric DNA
      under its G-quadruplex conformation are able to impair telomerase activity.
      Several recent reports have shown that G-quadruplex ligands could block
      telomerase activity in cancer cells and represent a new experimental approach to
      limit cancer growth. The intracellular existence of G-quadruplex structure is
      still controversial, since no direct proof allowed to establish its reality. Many
      sequences of nucleic acids in the mammalian genome are able to form a G
      quadruplex in vitro and several proteins have been described to interact in vitro
      with G-quadruplex. These data indicated that G-quadruplex are members of a family
      of target structures larger than that initially described at telomeres, and
      raised the question of the selectivity and therapeutic index of their ligands in
      the context of an antitumor therapy.

PMID- 12801814
TI  - [From cytogenetics to cytogenomics of brain tumors: 1. Medulloblastoma].
AB  - Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa
      in children. As prognostic factors for this disease are not well-established, it
      seemed important to identify genetic features in these tumors. We present data
      provided by recent studies on conventional cytogenetic, molecular cytogenetic and
      molecular genetic in correlation with prognosis in these tumors.

PMID- 12801815
TI  - [Radiation-induced skin reactions (except malignant tumors)].
AB  - The aim of this work, synthesized from personal case reports and a review of
      literature is to describe cutaneous complications of radiation therapy (except
      radiation-induced cancers): known and frequent such as radiation dermatitis or
      less frequent, beginning or strictly limited on irradiated skin areas: acne,
      infectious diseases, dyskeratosis, Grover's disease, sub-cutaneous pustulosis,
      cutaneous lichen, morphea, autoimmune bullous dermatosis, subacute cutaneous
      lupus erythematosus. Furthermore, we try to precise the physiopathogenic
      mechanisms of these dermatosis and we want to draw the attention on these
      dermatoses which sometimes need a multidisciplinary approach.

PMID- 12801816
TI  - [Cured of testicular cancer].
AB  - Nowadays, testicular cancer can be cured in more than 90 % of patients. Most
      patients we see now as "cured" of testicular cancer were treated either with
      chemotherapy or with radiotherapy. We detail the complete remission criteria and
      the follow-up procedure. We describe the long term toxicities of treatments, the
      risk of second cancer and the carryover of the disease and treatments on long
      term quality of life, sexuality and fertility.

PMID- 12801817
TI  - [Standards, Options and Recommendations for the management of invasive cervical
      cancer patients (non metastastic)].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of French Cancer Centers
      (FNCLCC), the 20 French cancer centers and specialists from French public
      university and general hospitals and private clinics. Its main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To develop, according to
      the definitions of the Standards, Options and Recommendations, clinical practice
      guidelines for the management of invasive cervical cancer patients. Methods :
      Data were identified by searching Medline and the personal reference lists of
      members of the expert groups, then submitted for review to independent reviewers.
      RESULTS: This is a synthesis of the Standards, Options and Recommendations
      elaborated by a working group of experts. Pretherapeutic assessment,
      classification, diagnosis, therapeutic modalities (surgery, radiotherapy,
      radiochemotherapy, chemotherapy), therapeutic strategies by disease stage and
      follow-up are covered. Algorithms for the management of patients are also
      included.

PMID- 12801818
TI  - [The choice of approach in the surgical management of endometrial carcinoma: a
      retrospective serie of 155 cases].
AB  - SETTING: Retrospective study of patients consecutively managed surgically for
      apparent stage I endometrial carcinoma in a comprehensive cancer center, using a
      standardized protocol for the choice of surgical approach: laparoscopically
      assisted vaginal hysterectomy (LAVH) as standard procedure, vaginal surgery in
      apparent stage IA grade 1 or in patients in poor medical condition, laparotomy in
      the case of subserous myometrial involvement at imaging or in patients with
      enlarged uteri or in the presence of a contra-indication to laparoscopy.
      MATERIALS AND METHODS: Excluding 2 patients in whom laparoscopy was converted in
      laparotomy, and 1 patient who had a full laparoscopic hysterectomy, the records
      of 155 patients were reviewed. All patients had a preoperative sonogram, and 74%
      had a preoperative MRI. Preoperative data, preoperative staging, operative data,
      pathological staging, postoperative complications, recurrence and survival were
      recorded. RESULTS: 69 patients (43.6%) had a LAVH procedure (group LAVH), 58
      patients (36.7%) were treated by laparotomy (group TAH), and 28 patients (18%)
      were treated by simple vaginal hysterectomy (group VH). Patients in the vaginal
      group were significantly heavier (VH 91.3 kg 33, range 53-175) than those of the
      other two groups (TAH 76.5 12.7, range 48-142; LAVH 71.1 18.5, range 47-102). The
      number of large (> 10 cm) uteri was significantly greater in the TAH group
      (46.5%) than the LAVH group (26.1%, p = 0.02) or the VH group (14.3%, p = 0.007).
      Myometrial invasion was suspected in 53.6% of the VH group, 72.6% of the LAVH
      group, and 71.4% of the TAH group. Deep myometrial invasion was suspected in no
      patient of the VH group, 14.5% of the LAVH group and 70.7% of the TAH group. The
      LAVH group had a significantly longer mean operative time than the TAH group or
      the VH group. The number of perioperative complications was significantly higher
      in the TAH group (22.4%) compared to the LAVH group (5.6%) and the VH group (0%).
      Blood loss was significantly elevated in the laparotomy group compared to the
      other two groups. The mean number of nodes removed was significantly higher in
      the LAVH group (15.8 7.8, range 4-37) compared to the TAH group (11 5.3, range 2
      25, p = 0.002). Of 155 patients, 100 (64.5%) had correct preoperative staging. In
      19 (12.3%), FIGO stage was overestimated preoperatively, and in 36 (23.2%) the
      FIGO stage was underestimated preoperatively. Survival curves were not found
      significantly different between groups.

PMID- 12801819
TI  - [Accuracy of intraoperative frozen section diagnosis in non palpable breast
      lesions: a series of 791 cases].
AB  - The aim of this study is to estimate the accuracy and reliability of
      intraoperative frozen section of nonpalpable breast lesions. In fact, frozen
      section of palpable breast lesions has proven to be valid, but its use in breast
      infraclinic lesions has been discussed recently, with the publication of European
      recommendations. Diagnosis on frozen section was routinely performed in a serie
      of 791 patients with nonpalpable mammographically detected abnormalities breast
      lesions from January 1990 through July 2000. The initial frozen section diagnoses
      with known mammographic pattern were compared with the diagnoses obtained on
      permanent paraffin sections to estimate the accuracy of frozen sections. Frozen
      section diagnosis was delayed until final diagnosis assessed on permanent
      paraffin sections in only 8 cases (1%). Frozen section diagnoses were accurate in
      744 of 783 cases (95%). The diagnosis was modified on the basis of permanent
      sections in 39 cases; consisting of 39 false negative. No false positive
      diagnosis was noted. Sensitivity and specificity of frozen section diagnoses were
      87,69 and 100, respectively. When the comparison between frozen and permanent
      section was analyzed according to the mammographic pattern, the sensitivity among
      patients with microcalcifications was lower (75,23) than among patients with
      opacities (93,86). When frozen section and permanent section diagnoses were
      related according to the mammographic size ( 10 mm) the sensitivity among
      patients with opacities measuring less than 10 mm was lower (91,75) than among
      patients with opacities larger than 10 mm (95,65) and the sensitivity among
      patients with microcalcifications larger than 10 mm was greater (77,14) than
      among patients with microcalcifications size less than 10 mm (74,28). This
      results are similar to those obtained on palpable breast lesions, and show that
      frozen section is a feasible and reliable procedure in nonpalpable breast
      lesions, particularly more relevant in mammographic opacities than in
      microcalcifications, whatever the lesion size.

PMID- 12801820
TI  - [Clinical practice guidelines in cancerology: comparative study of three decision
      support-systems for breast and prostate cancer in Lorraine french region].
AB  - Oncolor, the French regional cancer network of Lorraine, proposes clinical
      guidelines for the diagnosis, the treatment and the follow-up of cancers. In
      addition to paper documents, two computerized supports, a web site and the
      Kasimir software have been developed to make the use of these guidelines and
      their updating easier. This study aims at evaluating these three tools in breast
      and prostate cancer and to determine if computerized supports provide an
      additional help and an added value. From May to July 2001, 25 physicians of the
      Oncolor network have analysed, by consulting the guidelines on each of the 3
      supports, 23 clinical cases of breast cancer and 22 cases of prostate cancer,
      i.e. in total 1,293 cases. We observe for breast cancer a response rate
      consistent with the guideline significantly higher with the Kasimir software
      compared to paper (87.1% versus 77.8%) or to Internet (87.1% versus 75.8%), an
      optimisation of the recourse to a specialised physician or a pluridisciplinary
      committee and globally a good satisfaction of the users. These results induce us
      to continue with the Kasimir experiment, to develop it for other cancers,
      especially those with a complex management and to evaluate its impact on medical
      practices.

PMID- 12801821
TI  - [Chemotherapy of advanced non-small cell lung neoplasms: a closed debate?].

PMID- 12801822
TI  - [Frequency of cancer in France].
AB  - The most recent cancer mortality and morbidity data available for France are
      presented. In 1999, tumours are the first cause of death among men (87,000
      deaths) and the second most common among women (57,000 deaths) after
      cardiovascular diseases. It is also the most common cause of death in both the
      male and female populations aged 35 to 74. Lung cancer is the most common cause
      of cancer death (21,000) in the male population, and breast cancer is the most
      common cause of death (11,000) in the female population. Cancer mortality rates
      decrease both in the male population since 1987 and in the female population
      since 1950, but the different sites present different trends. The total number of
      cancers diagnosed in 2000 is estimated to be equal to 260,000: 149,000 in the
      male population and 108,000 in the female population. The most frequent cancer
      sites are prostate among men (28,000 cases) and breast among women (37,000
      cases), two sites for which screening activities are in widespread use.

PMID- 12801823
TI  - [Management of dyspnea in the cancer patient].
AB  - Dyspnea is a very common symptom in cancer patients. It is an important symptom
      because it interferes with patient's quality of life and because its treatment is
      often difficult. Dyspnea may be defined as an uncomfortable awareness of
      breathing. Diagnosis relies on physical examination, which intends also to assess
      severity of dyspnea and etiology. In cancer patients many mechanisms may be
      involved: tumor progression, side effects of treatments, associated disease
      especially from cardiac or infectious origin. A specific treatment (whenever it
      is possible) is associated with symptomatic measures. Oxygen therapy is often
      used. Morphine can decrease the sensation of dyspnea by its central effects and
      is useful especially in palliative setting. Benzodiazepines reduce anxiety
      induced by dyspnea. Physiotherapy, support of patient and family must not be
      neglected.

PMID- 12801824
TI  - [Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of
      the management of cancer of the breast].
AB  - Within the past decades there has been major interest in associating the
      paclitaxel into the management of breast cancer patients with a strong
      improvement of clinical results. Moreover, doxorubicin is historically one of the
      major chemotherapeutic agents in breast cancer treatment. So, investigations of
      the combination of the paclitaxel with doxorubicin have logically taken place in
      the strategy of breast cancer management. Also, this association became a
      standard of care neoadjuvantly in locally advanced breast cancer. The aim of this
      review of literature consists to make a special focus on cardiac toxicity
      occurring after doxorubicin and paclitaxel association and to give adequate
      directions for the next future in this promising combination.

PMID- 12801825
TI  - [Gene therapy of childhood cancers: current status and perspectives].
AB  - Despite the extraordinary successes of treatments for paediatric malignancies
      over the last 30 years, almost 30% of patients will remain refractory or will
      relapse after conventional or intensified therapeutic regimen. Even when
      successful, the long-term sequelae of current treatments include severe organ
      toxicity and secondary malignancies. It is becoming evident that cellular and
      gene transfer approaches can induce remissions in some paediatric tumours and may
      be useful adjuvants for others. The most convincing approach to date has been to
      induce antitumour immunity either by rendering tumour cells more immunogenic by
      genetic modification or by improving the effector activity of the host's immune
      cells. These approaches may be expected to become more successful as we learn
      more of the mechanisms tumor cells use to evade the immune response, and exploit
      gene transfer to overcome these tumor-defence mechanisms. Gene transfer may also
      be used to reverse the malignant process, modulate tumour invasiveness or enhance
      the susceptibility of tumour cells to cytotoxic drugs, but these approaches are
      at an earlier stage of development and are limited by vector deficiencies. As
      vector technology improves, and with an improved understanding of the oncogenic
      process we may expect these additional approaches more broadly applied and making
      a significant contribution to the ultimate goal of targeted therapy for
      paediatric malignancy.

PMID- 12801826
TI  - [A symphony for the camptothecins].
AB  - Cancer occurs and it is life that runs off the rails. To restore the melody, the
      oncologist can use an array of pharmacological instruments which he needs to tune
      optimally to reach the maximal efficacy. Camptothecin derivatives, inhibitors of
      topoisomerase I, represent an essential family of the chemotherapeutic arsenal.
      Topotecan and irinotecan have been used in the clinic for a number of years, but
      other potent analogues are appearing and broaden the range of topoisomerase I
      poisons. In this review, we present the main molecular characteristics of the
      second generation of camptothecins (lurtotecan, exatecan, rubitecan, silatecan).
      The future is also evoked with camptothecin derivatives bearing a modified
      lactone ring, in particular the homocamptothecins and the drug diflomotecan,
      which shows promise as an anticancer. The camptothecin partition is disclosed
      here.

PMID- 12801827
TI  - [The sentinel lymph node in cancer of the breast: clinical aspects].
AB  - Sentinel lymph node (SLN) biopsy is effective to assess axillary nodal status and
      avoiding axillary lymph node dissection (ALND) in patients with clinically node
      negative early stage breast cancer. No standardization of the technique has yet
      been established. This review discusses the feasibility, the accuracy and the
      different techniques for this procedure. Although the SLN can be successfully
      identified by either the dye or gamma probe-guided method, its identification is
      facilitated when the two techniques are combined. To increase the sensitivity of
      the pathological examination of the SLN, it is necessary to make multiple step
      sections with hematoxylin and eosin staining immunohistochemistry on permanent
      sections. The intraoperative frozen sections and imprint cytology examinations of
      the SLN may be useful in determining its status, but further studies are needed
      to establish their performance. In clinical practice, routine ALND can be avoided
      for small tumours when the multidisciplinary team has an extensive experience of
      this technique. However, long-term regional control and survival have to be
      studied in prospective randomised trials, before SLN biopsy can replace routine
      ALND as the preferred staging method for women with localized breast cancer.

PMID- 12801828
TI  - [How to improve the initial management of adult patients with tumors of bone and
      soft tissues: the experience of a multidisciplinary committee from the Oncolor
      network before the distribution of regional guidelines].
AB  - Tumors of bone and soft tissues in adults are rare accounting in France for 2000
      to 2500 new cases per year. These tumors are heterogenous and their diagnosis is
      made after first surgery. Therefore, an early pluridisciplinary approach, by
      physicians who have acquired an expertise in this field, is advised before any
      biopsy or surgical resection and at all the further step in the subfrequent
      management. This paper describes the experience of a pluridisciplinary committee,
      specialized in malignant tumors of bone and soft tissues in adults, with a highly
      specialized team which is part of a network in the treatment of cancer in
      Lorraine, the Oncolor network, before the distribution of regional guidelines.
      After a description of the organisation of this committee, we made a
      retrospective analysis of all the cases submitted to these experts advice for the
      first time, between January and December 2000. This study reveals an insufficient
      pluridisciplinary coordination at the initial management, which has been done by
      making regional referentials available, and therefore some errors which lead in
      some cases to inadapted treatment. It underlines therefore the necessity to
      implement more actively the present data of science, and to develop the
      management in multidisciplinary committees. Oncolor aims to harmonize this
      pluridisciplinary approach as well as to diffuse standard recommendations.

PMID- 12801829
TI  - [From San Antonio to Saint-Gallen: reflections of Saint-Paul-de-Venice or how to
      treat breast cancer].

PMID- 12801830
TI  - [Limitations of palliative chemotherapy, application to lung cancer: the point of
      view of hospital pharmacists].
AB  - In our hospital, most of the patients with a cancer received palliative
      chemotherapy. Then, we wanted to know in which conditions these therapies were
      realised and most specially for patients with lung cancer. We noted the stage of
      the disease at the diagnosis, the median survival duration after diagnosis and
      the median time between the last treatment and death. We also noticed the
      chemotherapy incidents: decrease of dosage, postpone or cancel of a treatment,
      change of drugs. For the year 2000, 84 patients received chemotherapy, 30 died
      whom 17 with lung cancer. Diagnosis was done at a metastatic disease (stage IV)
      in 70.6% of patients with lung cancer. Then, median duration between diagnosis
      and death is 4 months, median time between last treatment and death is 13 days.
      Platinium's salts were chiefly used, combined with vinorelbine. 64.7% of patients
      with lung cancer had either toxicity or outlet, and 70.6% received a chemotherapy
      treatment during the last month before death. In our hospital, diagnosis of
      cancers specially lung cancers are late. Then, patients are treated palliatively
      with a small improvement and a not negligible toxicity. Therefore chemotherapy is
      carried on, even if it is hopeless.

PMID- 12801831
TI  - [A cancer research institute: of course and with an European vision as well].

PMID- 12801832
TI  - Erythropoietin therapy: need for rationality and active surveillance.

PMID- 12801833
TI  - When the bullet hits the target.

PMID- 12801834
TI  - Thrombosis and malignancy: an underestimated problem.

PMID- 12801835
TI  - The treatment of venous thromboembolic disorders: new challenges and
      opportunities.

PMID- 12801836
TI  - Homing of peripherally injected bone marrow cells in rat after experimental
      myocardial injury.
AB  - BACKGROUND AND OBJECTIVES: Significant progress has been achieved during the past
      10 years in cell transplantation and recent research has focused on the
      possibility of improving ventricular function after myocardial infarction. Most
      studies in the field of cardiac tissue repair are performed by direct
      intramyocardial injection of cells of different origin. Since this approach
      requires a surgical intervention, in this study we investigated the feasibility
      of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by
      assessing the fate of peripherally injected, purified, labeled cells in
      cryodamaged hearts. DESIGN AND METHODS: Ten donor and ten recipient inbred
      isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous
      transplantation. Myocardial damage was obtained in recipient rats by placing a
      frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze
      thaw injury technique). BMMNCs were purified and labeled with a red fluorescent
      cell dye. Seven days after the injury about 15-25x10(6) cells were infused
      through the femoral vein of recipient rats. Seven days after the infusion, the
      heart, lungs, liver, kidneys, spleen and thymus were harvested to track
      transplanted cells. RESULTS: Labeled cells were found only in the injured area of
      the heart and not in the normal tissue, and a limited number of cells were
      identified in the spleen of all the animals. Most of the labeled cells in the
      infarcted area were Thy-1(+) and some were CD34(+). INTERPRETATION AND
      CONCLUSIONS: Our data suggest that peripherally injected BMMNCs can traffic
      through the circulation to the site of damage; we hypothesize that tissue injury
      leads to the priming of a cytokine cascade acting as chemoattractant for the
      infused cells.

PMID- 12801837
TI  - p53 loss of function enhances genomic instability and accelerates clonal
      evolution of murine myeloid progenitors expressing the p(210)BCR-ABL tyrosine
      kinase.
AB  - BACKGROUND AND OBJECTIVES: The p210 bcr-abl fusion protein has a key role in the
      pathogenesis of chronic myeloid leukemia (CML). However, its influence on disease
      progression to blast crisis is marginal and mostly due to its effect of impairing
      the genomic stability of clonal myeloid progenitors through pathways still
      largely unknown. DESIGN AND METHODS: To elucidate the role of p53 in CML
      progression we generated, from the 32D murine myeloid cell line, several clones
      co-expressing the E6 product gene of human papilloma virus (HPV) 16, which
      abrogates p53 function, and a temperature-sensitive bcr-abl construct encoding a
      fully active p210 protein only at the permissive temperature of 33 degrees C.
      RESULTS: Co-expression of the two proteins resulted in a significant enlargement
      of the G(2)/M phase of cell cycle and in the appearance of a poly-aneuploid cell
      population. Furthermore, with continuous in vitro passages the p210 tyrosine
      kinase became dispensable for growth. Increased levels of cyclin B(1) and
      enhanced activity of its associated cyclin-dependent kinase (cdc2) became
      apparent during the clonal evolution of p210 bcr-abl-transduced 32D cell clones
      lacking p53. INTERPRETATION AND CONCLUSIONS: The acceleration of clonal evolution
      of p210 bcr-abl-transduced 32D myeloid progenitors associated with p53 functional
      abrogation is consistent with oncosuppressor loss having a key role in CML
      progression. This would allow emergence of additional genomic aberrations which
      would lead to the fully transformed phenotype of blast crisis. Deregulated
      activity of the cyclin B1-cdc2 complex may be involved in the loss of temporal co
      ordination of mitotic events and further free the barrier to genomic instability
      of CML clonal myeloid progenitors lacking p53.

PMID- 12801838
TI  - Erythroid bone marrow activity and red cell hemoglobinization in iron sufficient
      beta-thalassemia heterozygotes as reflected by soluble transferrin receptor and
      reticulocyte hemoglobin in content. Correlation with genotypes and Hb A(2)
      levels.
AB  - BACKGROUND AND OBJECTIVES: Ferrokinetic studies and erythroid cell
      ultrastructural studies have indicated some degree of ineffective erythropoiesis
      in heterozygous beta-thalassemia, although a wide case-to-case variation was
      observed. In this study we applied rapid biochemical and hematologic measurements
      to assess erythroid marrow activity (sTfR) and reticulocyte hemoglobin content
      (CHr) in iron-sufficient individuals with heterozygous beta-thalassemia and
      investigated the correlation with the degree of globin polypeptide chain
      imbalance by comparing parameters between beta-thalassemia heterozygotes with
      genotypes of variable severity. DESIGN AND METHODS: We studied 57 iron-sufficient
      adults with heterozygous beta-thalassemia, divided into groups according to
      genotype: group A: beta(silent)-thalassemia heterozygotes, group B: beta(+)
      thalassemia heterozygotes and group C: beta(0)-thalassemia heterozygotes. Twenty
      one hematologically normal individuals served as controls (group D). We measured
      hematologic parameters including CHr with a Bayer-Advia 120 hematology analyzer.
      Hemoglobins were analyzed by high performance liquid chromatography, while
      biochemical parameters of iron status (iron, ferritin, transferrin and sTfR) were
      measured with chemical, luminometric and nephelometric methods. RESULTS: We found
      significant positive correlations between sTfR values for all beta-thalassemia
      heterozygote groups when plotted against Hb A(2) and Hb F levels (r=0.566,
      p<0.0001 and r=0.283, p<0.03, respectively) and significantly negative
      correlation between CHr and Hb A(2) values (r=-0.790, p<0.00001). These data
      reflect the fine association of globin polypeptide chain imbalance with erythron
      expansion and the greater degree of ineffective erythropoiesis in beta
      thalassemia heterozygotes with more severe genotypes. INTERPRETATION AND
      CONCLUSIONS: This study is the first demonstration that sTfR and CHr are useful
      parameters for evaluating the relative severity of different genotypes in
      heterozygous beta-thalassemia.

PMID- 12801839
TI  - Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem
      duplication.
AB  - BACKGROUND AND OBJECTIVES: The biological characteristics and the prognostic
      significance of the internal tandem duplication of the FLT3 (FLT3/ITD) were
      investigated in a series of de novo acute myeloid leukemia (AML) patients. One
      hundred and fifty-six adult patients with AML were included in the study.
      FLT3/ITD was detected in 41 (26%) patients (FLT3/ITD(+)). DESIGN AND METHODS: The
      main differences observed between the groups with and without FLT3/ITD: a higher
      leukocyte count, a raised percentage of a normal karyotype and a more frequent M5
      FAB diagnosis in the FLT3/ITD(+) patients. As regards the immunophenotype
      characteristics the FLT3/ITD(+) group very often expressed monocytic markers
      (CD36 and CD11b) and less commonly immature markers (CD34 and CD117). A
      promyelocytic-like immunophenotype pattern was also detected in a minority of
      these patients(4/36). RESULTS: The FLT3/ITD(+) patients had a shorter overall
      survival, a shorter event-free survival and a higher probability of relapse.
      Minimal residual disease (MRD) was investigated in the FLT3/ITD(+) patients using
      flow cytometry. This technique had a sensitivity of 62% and a specificity of 83%
      in relapse prediction. Minimal residual disease analysis was hampered by the low
      number of patients with detectable aberrant immunophenotype. INTERPRETATION AND
      CONCLUSIONS: A high frequency of changes in the phenotype and/or genotype pattern
      between diagnosis and relapse was detected (5/6). FLT3/ITD is a frequent
      molecular lesion in de novo adult AML and seems to be associated with a monocytic
      differentiation, a high leukocyte count and a poor prognosis. Immunophenotype and
      genotype patterns observed at relapse suggest that the FLT3/ITD(+) blasts may be
      genetically unstable and prone to clonal evolution. FLT3/ITD may not be a
      suitable target for minimal residual disease studies.

PMID- 12801840
TI  - Detection of minimal residual disease in unselected patients with acute myeloid
      leukemia using multiparameter flow cytometry for definition of leukemia
      associated immunophenotypes and determination of their frequencies in normal bone
      marrow.
AB  - BACKGROUND AND OBJECTIVES: Detection of minimal residual disease (MRD) by
      multiparameter flow cytometry is an emerging prognostic factor in patients with
      acute myeloid leukemia (AML). The present analysis aimed at improving the
      applicability of this approach to more patients with AML. DESIGN AND METHODS:
      Bone marrow samples from unselected patients with AML at diagnosis and from
      healthy volunteers were immunophenotyped applying triple-stainings of 31
      antigens. Leukemia-associated immunophenotypes were defined by gating on
      populations displaying an aberrant or infrequent immunophenotype and by applying
      Boolean algebra. The combination of gates obtained was applied to list mode data
      files containing measurements of normal bone marrow samples. Dilution experiments
      of AML samples in normal bone marrow were performed to test the linearity of
      measurements. RESULTS: At least one aberrant/infrequent immunophenotype was
      identified (median, 2; range, 1-5) in all of 68 analyzed AML patients. The median
      frequencies of cells displaying an aberrant/infrequent immunophenotype within
      normal bone marrow ranged from 0.00% to 1.20% (median, 0.07%). Limiting this
      analysis to only the most sensitive aberrant/infrequent immunophenotype per
      patient resulted in frequencies of cells displaying an aberrant/infrequent
      immunophenotype within normal bone marrow ranging from 0.00% to 0.43% (median,
      0.05%). Serial dilution experiments confirmed the linearity of measurements
      (R>0.90 in all cases analyzed). INTERPRETATION AND CONCLUSIONS: The application
      of multiparameter flow cytometry to identify cells displaying an
      aberrant/infrequent immunophenotype and to quantify MRD is feasible in unselected
      patients with AML.

PMID- 12801841
TI  - Lymphotoxin beta expression is high in chronic lymphocytic leukemia but low in
      small lymphocytic lymphoma: a quantitative real-time reverse transcriptase
      polymerase chain reaction analysis.
AB  - BACKGROUND AND OBJECTIVES: The lymphotoxin beta (LTB) gene, localized to the
      major histocompatibility complex region on chromosome 6p21.3, has an important
      role in the formation of germinal center reactions and regulation of immune
      response and apoptosis. Our aim was to determine LTB gene expression in different
      hematologic neoplasias. DESIGN AND METHODS: We determined the expression of LTB
      using quantitative real-time reverse transcriptase polymerase chain reaction (RT
      PCR) on a series of RNA samples from CD3(+) T cells and CD19(+) B cells isolated
      from peripheral blood (n=7); CD19(+) B cells isolated from lymph nodes (n=11) and
      from patients with acute lymphoblastic leukemia (ALL; n=16), acute myeloid
      leukemia (AML; n=43), chronic myeloid leukemia (CML; n=12), mantle cell lymphoma
      (MCL; n=19), chronic lymphocytic leukemia (CLL; n=32) and small lymphocytic
      lymphoma (SLL; n=22). RESULTS: The expression level of LTB in CD3(+) T cells and
      CD19(+) B cells isolated from blood was ten to forty times lower than that in
      normal CD19(+) B cells isolated from lymph nodes. In malignant myeloid cells the
      expression levels were very low, whereas in malignant lymphoid cells the
      expression was higher than in myeloid cells, being highest in MCL and CLL (20.2+/
      14.0 ng/microL and 81.0+/-116.3 ng/microL) and low in SLL (4.5+/-3.6 ng/microL;
      p=0.001). We did not find correlations between LTB expression and hematoclinical
      parameters (risk groups, immunophenotypes and overall survival). INTERPRETATION
      AND CONCLUSIONS: A distinct difference in expression of LTB in CLL and SLL
      indicates that these morphologically similar B-cell malignancies are molecularly
      different. Further studies are needed to investigate the prognostic value of LTB
      and any role that LTB may have in determining whether the malignant B cells
      manifest a leukemia or lymphoma.

PMID- 12801843
TI  - B-cell non-Hodgkin's lymphomas express heterogeneous patterns of
      neovascularization.
AB  - BACKGROUND AND OBJECTIVES: The role of angiogenesis in the growth and survival of
      hematologic malignancies was not clear until recently. We have previously
      demonstrated in beta-cell non Hodgkin's lymphomas (B-NHL), that neoplastic
      progression, as defined by its increasing malignancy grades, is clearly related
      to the degree of angiogenesis. DESIGN AND METHODS: In the present study we used
      transmission electron microscopy to examine the ultrastructural patterns of
      neovascularization in both low and high grade B-NHL). In low grade B-NHL the
      vessel lumen was formed either by endothelial cell body curving or, more
      frequently, by the fusion of intracellular vacuoles in poorly differentiated
      endothelial cells. In high grade B-NHL, on the other hand, the predominant neo
      angiogenic pattern was the formation of a slit-like lumen. A remarkable
      ultrastructural feature in high-grade B-NHL was the intimate relationship between
      endothelial and tumor cells. Both low and high grade B-NHL exhibited development
      of transluminal bridges in larger vessels, leading to the division of the vessel.
      INTERPRETATION AND CONCLUSIONS: These in situ data suggest that the intrinsic
      process of endothelial cell proliferation and vessel formation in the stroma of B
      NHL varies according to the grade of tumor malignancy and point to the important
      role played by the specific organ microenvironment, which determines the extent
      of cancer cell proliferation, angiogenesis and invasion. In fact, the
      microenvironment has an important influence on vascular architecture, i.e., the
      properties of tumor cells can also determine the outcome of the angiogenic
      response. Taken together our findings, which provide quantitative data on
      different vascular patterns in B-NHL, have potential implications for vascular
      targeting and cancer therapy.

PMID- 12801842
TI  - Molecular immunoglobulin/T- cell receptor clonality analysis in cutaneous
      lymphoproliferations. Experience with the BIOMED-2 standardized polymerase chain
      reaction protocol.
AB  - BACKGROUND AND OBJECTIVES: Molecular clonality analysis of immunoglobulin (Ig)
      and T-cell receptor (TCR) genes is a widely used diagnostic tool for
      discrimination between polyclonal, oligoclonal, and monoclonal
      lymphoproliferative skin lesions. We studied Ig/TCR clonality in a series of 60
      patients with an initial suspicion of (primary) cutaneous B- or T-cell lymphoma
      (CBCL/CTCL). Clonality of Ig/TCR gene rearrangements was assessed by Southern
      blot (SB) and polymerase chain reaction (PCR) analysis using standardized PCR
      primers and protocols of the BIOMED-2 Concerted Action BMH4-CT98-3936. The
      obtained PCR products were subjected to heteroduplex (HD) and GeneScan (GS)
      analysis. We compared the data of 154 samples with the histopathologic diagnosis,
      based on the EORTC classification of skin lymphomas. DESIGN AND METHODS:
      Molecular results were largely concordant with histopathology. In 12 CBCL
      patients PCR analysis of Ig gene rearrangements detected clonality in 83% of
      cases whereas SB did so in 92%. Clonal TCR gene rearrangements were detected by
      SB in 68% of CTCL patients, whereas TCRG and TCRB PCR analysis detected clonality
      in 76% and 66% of cases, respectively. PCR GS analysis of TCR rearrangements
      appeared to be slightly more informative than HD analysis. Clonality assessment
      was particularly informative for studying involvement of extracutaneous sites,
      such as regional lymph nodes, peripheral blood, and bone marrow. INTERPRETATION
      AND CONCLUSIONS: Our study shows that the BIOMED-2 multiplex PCR analysis
      strategy is a reliable and useful technique in the diagnostic process of patients
      with an initial suspicion of (primary) CBCL/CTCL and for assessment of
      extracutaneous dissemination, provided that the results are interpreted in the
      context of clinical, histologic and immunophenotypic data.

PMID- 12801844
TI  - Low platelet counts alone do not cause bleeding in an experimental immune
      thrombocytopenic purpura in mice.
AB  - BACKGROUND AND OBJECTIVES: The physiopathogenesis of hemorrhagic phenomena in
      patients with autoimmune thrombocytopenic purpura is associated with low platelet
      levels. In the present work the relation between thrombocytopenia and bleeding
      was examined. The possible participation of endothelial cells in bleeding was
      also investigated. DESIGN AND METHODS: Immune thrombocytopenia and bleeding were
      studied in mice injected with anti-mouse and anti-human platelet polyclonal
      rabbit IgG. Platelet levels were measured at different times and bleeding signs
      were systematically recorded. ANOVA tests were used to compare platelet levels.
      Binding of anti-platelet antibodies to vascular endothelial cells was analyzed by
      immunohistochemistry. RESULTS: Three different doses of anti-platelet IgG caused
      the same low platelet levels, but bleeding occurred only with high doses of anti
      platelet IgG irrespective of the platelet levels. No inflammation around blood
      vessels was observed in paraffin-embedded tissue sections of organs.
      Immunohistochemistry demonstrated anti-platelet antibodies bound to vascular
      endothelium. INTERPRETATION AND CONCLUSIONS: We showed lack of correlation
      between platelet counts and bleeding in a murine model. The binding of anti
      platelet IgG to endothelial cells of small vessels is an indication that antibody
      mediated endothelial activation, in addition to thrombocytopenia, could be
      participating in bleeding.

PMID- 12801845
TI  - Fainting induces an acute increase in the concentration of plasma factor VIII and
      von Willebrand factor.
AB  - BACKGROUND AND OBJECTIVES: von Willebrand factor (VWF) is stored in the Weibel
      Palade bodies of endothelial cells and may be released in response to different
      secretion stimuli such as stress, physical exercise, adrenaline, DDAVP and
      thrombin. DESIGN AND METHODS: We found that fainting can also induce an acute
      increase in plasma VWF and factor FVIII (FVIII) concentrations, following
      observations in two patients with von Willebrand's disease (VWD) who experienced
      a fainting episode during venipuncture for blood collection. RESULTS: One patient
      was classified as having type Vicenza VWD, the other as type 1 VWD; both had
      normal platelet VWF content. After the fainting episode, FVIII and VWF levels
      were significantly higher than the levels in blood samples collected without
      stress; mean increases were 4.35-fold for FVIII, 4-fold for VWF:Ag and 5.3-fold
      for VWF:RCo, with values overshooting the upper limit of the normal range.
      Moreover, the post-fainting plasma VWF multimer pattern was characterized by a
      significant increase in all oligomers with the appearance of unusually large VWF
      multimers, similar to those observed following DDAVP infusion. INTERPRETATION AND
      CONCLUSIONS: These findings demonstrate that fainting acts as a stimulus capable
      of inducing the release of VWF from endothelial cells, and further highlight the
      role of stress in determining hemostatic states potentially favorable to the
      development of thrombotic complications.

PMID- 12801846
TI  - Effect of unfractionated heparin and a low molecular weight heparin (enoxaparin)
      on coagulant activity of cultured human endothelial cells.
AB  - BACKGROUND AND OBJECTIVES: Unfractionated heparin and low molecular weight
      heparins exert their anticoagulant effect by mobilizing tissue factor pathway
      inhibitor (TFPI) from the vascular endothelium into the blood circulation. We
      compared the influence of unfractionated heparin and enoxaparin on the
      anticoagulant function of cultured human endothelial cells. DESIGN AND METHODS:
      Monolayers of human umbilical vein endothelial cells were treated with 10 U/mL
      unfractionated heparin or enoxaparin for different periods of time (30min-48h).
      Endothelial cell procoagulant activity was determined in the cell lysates by a
      chromogenic assay. Endothelial cell tissue factor (TF) and released TFPI and von
      Willebrand factor (vWF) was determined. RESULTS: In short periods of incubation
      (30min-2h), both heparins reduced endothelial cell procoagulant activity, the
      inhibition produced by unfractionated heparin being greater than that induced by
      enoxaparin (p<0.05). However, no variations were observed in TFPI and vWF
      release. With long periods of incubation (24-48h), both unfractionated heparin
      and enoxaparin significantly increased TFPI release (control vs. unfractionated
      heparin, p<0.05-0.001; control vs. enoxaparin, p<0.01-0.001) and also reduced the
      release of vWF in the culture medium, though no variations in endothelial cell
      procoagulant activity or TF content were observed. INTERPRETATION AND
      CONCLUSIONS: Our findings show that unfractionated heparin and enoxaparin exert
      different kinds of effects on endothelial cells. With short incubation periods,
      procoagulant endothelial cell capacity was reduced to a greater extent by
      unfractionated heparin, while after longer periods of incubation enoxapain
      increased the anticoagulant activity of the endothelial cells to a greater degree
      than did unfractionated heparin.

PMID- 12801847
TI  - International and Italian prognostic indices in follicular lymphoma.
AB  - BACKGROUND AND OBJECTIVES: The International Prognostic Index (IPI), initially
      designed for aggressive lymphomas, has been successfully used in patients with
      follicular lymphoma (FL). The Italian Lymphoma Intergroup (ILI) created a new
      prognostic index specific for FL. The aim of this study was to compare which of
      these two indices is more useful when applied to a large group of FL patients.
      DESIGN AND METHODS: Both indices, IPI (age >60 years, extranodal involvement >=2
      sites, elevated lactate dehydrogenase, ECOG >=2, stage >=3) and ILI (age >60
      years, extranodal involvement >=2 sites, elevated lactate dehydrogenase, male
      sex, B symptoms, erythrocyte sedimentation rate >=30 mm 1(st) hour) were
      calculated in a group of 398 FL patients. Overall survival (OS) and progression
      free survival (PFS) associated with each prognostic group were calculated
      according to the Kaplan-Meier method. RESULTS: The overall concordance between
      both indices was 73%. According to the IPI 122 patients (31%) were in the higher
      risk group, whereas according to the ILI 132 (33%) were; concordance between the
      high risk groups was 66%. The 10-years OS and PFS rates after applying the IPI
      system were 73% and 37%, respectively, in the low risk groups; 47% and 26%, in
      the intermediate risk groups and 25% and 2%, in the high risk groups (log
      rank=69.2 and 41.3, respectively; p<0.0001). According to ILI index the 10-year
      OS and PFS were 60% and 34%, respectively, in the low risk groups; 59% and 30%,
      in the intermediate risk groups and 17% and 0%, in the high risk groups (log
      rank=86.6 and 58.5, respectively; p<0.0001). INTERPRETATION AND CONCLUSIONS: Both
      the IPI and ILI index, are useful for classifying FL patients into different risk
      groups. Although it seems that the ILI index has a higher discriminating power
      among groups, significant differences were not observed in identifying FL
      patients with a poor outcome.

PMID- 12801848
TI  - Levels of coagulation factors and venous thromboembolism.
AB  - BACKGROUND AND OBJECTIVES: Altered levels of coagulation factors have been
      included among the abnormalities that may increase the risk of venous
      thromboembolism (VTE) in otherwise healthy subjects. INFORMATION SOURCES:
      According to the studies that have been carried to test this hypothesis only
      elevated levels of factor VIII and fibrinogen emerged as independent risk factors
      for VTE. STATE OF THE ART AND PERSPECTIVES: Although some data indicate that
      elevated levels of factor XI or IX are also determinants for VTE, this awaits
      confirmation.

PMID- 12801849
TI  - The influence of exercise on serum markers of altered erythropoiesis and the
      indirect detection models of recombinant human erythropoietin abuse in athletes.

PMID- 12801850
TI  - Isochromosome 17q in patients with myelodysplastic syndromes: six new cases.

PMID- 12801851
TI  - Evaluation of leukemic contamination in peripheral blood stem cell leukaphereses
      vs bone marrow after consolidation therapy in acute myeloid leukemia: not a
      critical factor in outcome?

PMID- 12801852
TI  - Once weekly recombinant human erythropoietin therapy is very efficient after
      allogeneic peripheral blood stem cell transplantation when started soon after
      engraftment.

PMID- 12801853
TI  - Combination of congenital coagulation disorders: Factor II gene mutation G20210A,
      Factor V Leiden gene mutation G1691A and protein S deficiency. a family study.

PMID- 12801854
TI  - Acute renal cortex necrosis caused by arterial thrombosis during treatment for
      acute promyelocytic leukemia.

PMID- 12801856
TI  - Unusual presentation of Hodgkin lymphoma.

PMID- 12801855
TI  - Fulminant hepatitis subsequent to reactivation of precore mutant hepatitis B
      virus in a patient with lymphoma treated with chemotherapy and rituximab.

PMID- 12801857
TI  - Highly sensitive quantification of human cells in chimeric NOD/SCID mice by real
      time PCR.

PMID- 12801858
TI  - Cardiac surgery and paroxysmal noctural hemoglobinuria.

PMID- 12801859
TI  - Angiopoietins expression by human myeloma cells.

PMID- 12801863
TI  - New analytical techniques for the interpretation of microarray data. Proceedings
      from the NIPS Workshop on Machine Learning Techniques for Bioinformatics. British
      Columbia, Canada, December 2001.

PMID- 12801861
TI  - Quantification of CD34 epitopes in AML.

PMID- 12801864
TI  - Modified nonparametric approaches to detecting differentially expressed genes in
      replicated microarray experiments.
AB  - MOTIVATION: An important goal in analyzing microarray data is to determine which
      genes are differentially expressed across two kinds of tissue samples or samples
      obtained under two experimental conditions. Various parametric tests, such as the
      two-sample t-test, have been used, but their possibly too strong parametric
      assumptions or large sample justifications may not hold in practice. As
      alternatives, a class of three nonparametric statistical methods, including the
      empirical Bayes method of Efron et al. (2001), the significance analysis of
      microarray (SAM) method of Tusher et al. (2001) and the mixture model method
      (MMM) of Pan et al. (2001), have been proposed. All the three methods depend on
      constructing a test statistic and a so-called null statistic such that the null
      statistic's distribution can be used to approximate the null distribution of the
      test statistic. However, relatively little effort has been directed toward
      assessment of the performance or the underlying assumptions of the methods in
      constructing such test and null statistics. RESULTS: We point out a problem of a
      current method to construct the test and null statistics, which may lead to
      largely inflated Type I errors (i.e. false positives). We also propose two
      modifications that overcome the problem. In the context of MMM, the improved
      performance of the modified methods is demonstrated using simulated data. In
      addition, our numerical results also provide evidence to support the utility and
      effectiveness of MMM.

PMID- 12801865
TI  - Statistical adjustment of signal censoring in gene expression experiments.
AB  - MOTIVATION: Numerical output of spotted microarrays displays censoring of pixel
      intensities at some software dependent threshold. This reduces the quality of
      gene expression data, because it seriously violates the linearity of expression
      with respect to signal intensity. Statistical methods based on typically
      available spot summaries together with some parametric assumptions can suggest
      ways to correct for this defect. RESULTS: A maximum likelihood approach is
      suggested together with a sensible approximation to the joint density of the
      mean, median and variance-which are typically available to the biological end
      user. The method 'corrects' the gene expression values for pixel censoring. A by
      product of our approach is a comparison between several two-parameter models for
      pixel intensity values. It suggests that pixels separated by one or two other
      pixels can be considered independent draws from a Lognormal or a Gamma
      distribution. AVAILABILITY: The R/S-Plus code is available at
      http://www.stats.gla.ac.uk/~microarray/software.

PMID- 12801866
TI  - Boosting for tumor classification with gene expression data.
AB  - MOTIVATION: Microarray experiments generate large datasets with expression values
      for thousands of genes but not more than a few dozens of samples. Accurate
      supervised classification of tissue samples in such high-dimensional problems is
      difficult but often crucial for successful diagnosis and treatment. A promising
      way to meet this challenge is by using boosting in conjunction with decision
      trees. RESULTS: We demonstrate that the generic boosting algorithm needs some
      modification to become an accurate classifier in the context of gene expression
      data. In particular, we present a feature preselection method, a more robust
      boosting procedure and a new approach for multi-categorical problems. This allows
      for slight to drastic increase in performance and yields competitive results on
      several publicly available datasets. AVAILABILITY: Software for the modified
      boosting algorithms as well as for decision trees is available for free in R at
      http://stat.ethz.ch/~dettling/boosting.html.

PMID- 12801867
TI  - K-ary clustering with optimal leaf ordering for gene expression data.
AB  - MOTIVATION: A major challenge in gene expression analysis is effective data
      organization and visualization. One of the most popular tools for this task is
      hierarchical clustering. Hierarchical clustering allows a user to view
      relationships in scales ranging from single genes to large sets of genes, while
      at the same time providing a global view of the expression data. However,
      hierarchical clustering is very sensitive to noise, it usually lacks of a method
      to actually identify distinct clusters, and produces a large number of possible
      leaf orderings of the hierarchical clustering tree. In this paper we propose a
      new hierarchical clustering algorithm which reduces susceptibility to noise,
      permits up to k siblings to be directly related, and provides a single optimal
      order for the resulting tree. RESULTS: We present an algorithm that efficiently
      constructs a k-ary tree, where each node can have up to k children, and then
      optimally orders the leaves of that tree. By combining k clusters at each step
      our algorithm becomes more robust against noise and missing values. By optimally
      ordering the leaves of the resulting tree we maintain the pairwise relationships
      that appear in the original method, without sacrificing the robustness. Our k-ary
      construction algorithm runs in O(n(3)) regardless of k and our ordering algorithm
      runs in O(4(k)n(3)). We present several examples that show that our k-ary
      clustering algorithm achieves results that are superior to the binary tree
      results in both global presentation and cluster identification. AVAILABILITY: We
      have implemented the above algorithms in C++ on the Linux operating system.

PMID- 12801868
TI  - Coupled two-way clustering analysis of breast cancer and colon cancer gene
      expression data.
AB  - We present and review coupled two-way clustering, a method designed to mine gene
      expression data. The method identifies submatrices of the total expression
      matrix, whose clustering analysis reveals partitions of samples (and genes) into
      biologically relevant classes. We demonstrate, on data from colon and breast
      cancer, that we are able to identify partitions that elude standard clustering
      analysis. AVAILABILITY: Free, at http://ctwc.weizmann.ac.il.. SUPPLEMENTARY
      INFORMATION: http://www.weizmann.ac.il/physics/complex/compphys/bioinfo2/

PMID- 12801869
TI  - Bagging to improve the accuracy of a clustering procedure.
AB  - MOTIVATION: The microarray technology is increasingly being applied in biological
      and medical research to address a wide range of problems such as the
      classification of tumors. An important statistical question associated with tumor
      classification is the identification of new tumor classes using gene expression
      profiles. Essential aspects of this clustering problem include identifying
      accurate partitions of the tumor samples into clusters and assessing the
      confidence of cluster assignments for individual samples. RESULTS: Two new
      resampling methods, inspired from bagging in prediction, are proposed to improve
      and assess the accuracy of a given clustering procedure. In these ensemble
      methods, a partitioning clustering procedure is applied to bootstrap learning
      sets and the resulting multiple partitions are combined by voting or the creation
      of a new dissimilarity matrix. As in prediction, the motivation behind bagging is
      to reduce variability in the partitioning results via averaging. The performances
      of the new and existing methods were compared using simulated data and gene
      expression data from two recently published cancer microarray studies. The bagged
      clustering procedures were in general at least as accurate and often
      substantially more accurate than a single application of the partitioning
      clustering procedure. A valuable by-product of bagged clustering are the cluster
      votes which can be used to assess the confidence of cluster assignments for
      individual observations. SUPPLEMENTARY INFORMATION: For supplementary information
      on datasets, analyses, and software, consult
      http://www.stat.berkeley.edu/~sandrine and http://www.bioconductor.org.

PMID- 12801870
TI  - Simultaneous gene clustering and subset selection for sample classification via
      MDL.
AB  - MOTIVATION: The microarray technology allows for the simultaneous monitoring of
      thousands of genes for each sample. The high-dimensional gene expression data can
      be used to study similarities of gene expression profiles across different
      samples to form a gene clustering. The clusters may be indicative of genetic
      pathways. Parallel to gene clustering is the important application of sample
      classification based on all or selected gene expressions. The gene clustering and
      sample classification are often undertaken separately, or in a directional manner
      (one as an aid for the other). However, such separation of these two tasks may
      occlude informative structure in the data. Here we present an algorithm for the
      simultaneous clustering of genes and subset selection of gene clusters for sample
      classification. We develop a new model selection criterion based on Rissanen's
      MDL (minimum description length) principle. For the first time, an MDL code
      length is given for both explanatory variables (genes) and response variables
      (sample class labels). The final output of the proposed algorithm is a sparse and
      interpretable classification rule based on cluster centroids or the closest genes
      to the centroids. RESULTS: Our algorithm for simultaneous gene clustering and
      subset selection for classification is applied to three publicly available data
      sets. For all three data sets, we obtain sparse and interpretable classification
      models based on centroids of clusters. At the same time, these models give
      competitive test error rates as the best reported methods. Compared with
      classification models based on single gene selections, our rules are stable in
      the sense that the number of clusters has a small variability and the centroids
      of the clusters are well correlated (or consistent) across different cross
      validation samples. We also discuss models where the centroids of clusters are
      replaced with the genes closest to the centroids. These models show comparable
      test error rates to models based on single gene selection, but are more sparse as
      well as more stable. Moreover, we comment on how the inclusion of a
      classification criterion affects the gene clustering, bringing out class
      informative structure in the data. AVAILABILITY: The methods presented in this
      paper have been implemented in the R language. The source code is available from
      the first author.

PMID- 12801871
TI  - Novel clustering algorithm for microarray expression data in a truncated SVD
      space.
AB  - MOTIVATION: This paper introduces the application of a novel clustering method to
      microarray expression data. Its first stage involves compression of dimensions
      that can be achieved by applying SVD to the gene-sample matrix in microarray
      problems. Thus the data (samples or genes) can be represented by vectors in a
      truncated space of low dimensionality, 4 and 5 in the examples studied here. We
      find it preferable to project all vectors onto the unit sphere before applying a
      clustering algorithm. The clustering algorithm used here is the quantum
      clustering method that has one free scale parameter. Although the method is not
      hierarchical, it can be modified to allow hierarchy in terms of this scale
      parameter. RESULTS: We apply our method to three data sets. The results are very
      promising. On cancer cell data we obtain a dendrogram that reflects correct
      groupings of cells. In an AML/ALL data set we obtain very good clustering of
      samples into four classes of the data. Finally, in clustering of genes in yeast
      cell cycle data we obtain four groups in a problem that is estimated to contain
      five families. AVAILABILITY: Software is available as Matlab programs at
      http://neuron.tau.ac.il/~horn/QC.htm.

PMID- 12801872
TI  - Learning rule-based models of biological process from gene expression time
      profiles using gene ontology.
AB  - MOTIVATION: Microarray technology enables large-scale inference of the
      participation of genes in biological process from similar expression profiles.
      Our aim is to induce classificatory models from expression data and biological
      knowledge that can automatically associate genes with novel hypotheses of
      biological process. RESULTS: We report a systematic supervised learning approach
      to predicting biological process from time series of gene expression data and
      biological knowledge. Biological knowledge is expressed using gene ontology and
      this knowledge is associated with discriminatory expression-based features to
      form minimal decision rules. The resulting rule model is first evaluated on genes
      coding for proteins with known biological process roles using cross validation.
      Then it is used to generate hypotheses for genes for which no knowledge of
      participation in biological process could be found. The theoretical foundation
      for the methodology based on rough sets is outlined in the paper, and its
      practical application demonstrated on a data set previously published by Cho et
      al. (Nat. Genet., 27, 48-54, 2001). AVAILABILITY: The Rosetta system is available
      at http://www.idi.ntnu.no/~aleks/rosetta. SUPPLEMENTARY INFORMATION:
      http://www.lcb.uu.se/~hvidsten/bioinf_cho/

PMID- 12801873
TI  - Gene interaction in DNA microarray data is decomposed by information geometric
      measure.
AB  - MOTIVATION: Given the vast amount of gene expression data, it is essential to
      develop a simple and reliable method of investigating the fine structure of gene
      interaction. We show how an information geometric measure achieves this. RESULTS:
      We introduce an information geometric measure of binary random vectors and show
      how this measure reveals the fine structure of gene interaction. In particular,
      we propose an iterative procedure by using this measure (called IPIG). The
      procedure finds higher-order dependencies which may underlie the interaction
      between two genes of interest. To demonstrate the method, we investigate the
      interaction between the two genes of interest in the data from human acute
      lymphoblastic leukemia cells. The method successfully discovered biologically
      known findings and also selected other genes as hidden causes that constitute the
      interaction. AVAILABILITY: Softwares are currently not available but are possibly
      made available in future at
      http://www.mns.brain.riken.go.jp/~nakahara/DNA_pub.html where all the related
      information is also linked.

PMID- 12801874
TI  - Classification of multiple cancer types by multicategory support vector machines
      using gene expression data.
AB  - MOTIVATION: High-density DNA microarray measures the activities of several
      thousand genes simultaneously and the gene expression profiles have been used for
      the cancer classification recently. This new approach promises to give better
      therapeutic measurements to cancer patients by diagnosing cancer types with
      improved accuracy. The Support Vector Machine (SVM) is one of the classification
      methods successfully applied to the cancer diagnosis problems. However, its
      optimal extension to more than two classes was not obvious, which might impose
      limitations in its application to multiple tumor types. We briefly introduce the
      Multicategory SVM, which is a recently proposed extension of the binary SVM, and
      apply it to multiclass cancer diagnosis problems. RESULTS: Its applicability is
      demonstrated on the leukemia data (Golub et al., 1999) and the small round blue
      cell tumors of childhood data (Khan et al., 2001). Comparable classification
      accuracy shown in the applications and its flexibility render the MSVM a viable
      alternative to other classification methods. SUPPLEMENTARY INFORMATION:
      http://www.stat.ohio-state.edu/~yklee/msvm.htm

PMID- 12801875
TI  - eXPatGen: generating dynamic expression patterns for the systematic evaluation of
      analytical methods.
AB  - MOTIVATION: Experimental gene expression data sets, such as those generated by
      microarray or gene chip experiments, typically have significant noise and
      complicated interconnectivities that make understanding even simple regulatory
      patterns difficult. Given these complications, characterizing the effectiveness
      of different analysis techniques to uncover network groups and structures remains
      a challenge. Generating simulated expression patterns with known biological
      features of expression complexity, diversity and interconnectivities provides a
      more controlled means of investigating the appropriateness of different analysis
      methods. A simulation-based approach can systematically evaluate different gene
      expression analysis techniques and provide a basis for improved methods in
      dynamic metabolic network reconstruction. RESULTS: We have developed an on-line
      simulator, called eXPatGen, to generate dynamic gene expression patterns typical
      of microarray experiments. eXPatGen provides a quantitative network structure to
      represent key biological features, including the induction, repression, and
      cascade regulation of messenger RNA (mRNA). The simulation is modular such that
      the expression model can be replaced with other representations, depending on the
      level of biological detail required by the user. Two example gene networks, of 25
      and 100 genes respectively, were simulated. Two standard analysis techniques,
      clustering and PCA analysis, were performed on the resulting expression patterns
      in order to demonstrate how the simulator might be used to evaluate different
      analysis methods and provide experimental guidance for biological studies of gene
      expression. AVAILABILITY: http://www.che.udel.edu/eXPatGen/

PMID- 12801876
TI  - A statistical problem for inference to regulatory structure from associations of
      gene expression measurements with microarrays.
AB  - MOTIVATION: One approach to inferring genetic regulatory structure from
      microarray measurements of mRNA transcript hybridization is to estimate the
      associations of gene expression levels measured in repeated samples. The
      associations may be estimated by correlation coefficients or by conditional
      frequencies (for discretized measurements) or by some other statistic. Although
      these procedures have been successfully applied to other areas, their validity
      when applied to microarray measurements has yet to be tested. RESULTS: This paper
      describes an elementary statistical difficulty for all such procedures, no matter
      whether based on Bayesian updating, conditional independence testing, or other
      machine learning procedures such as simulated annealing or neural net pruning.
      The difficulty obtains if a number of cells from a common population are
      aggregated in a measurement of expression levels. Although there are special
      cases where the conditional associations are preserved under aggregation, in
      general inference of genetic regulatory structure based on conditional
      association is unwarranted

PMID- 12801877
TI  - Coupled two-way clustering server.
AB  - The CTWC server provides access to the software, CTWC1.00, that implements
      Coupled Two Way Clustering (Getz et al., 2000), a method designed to mine gene
      expression data AVAILABILITY: Free, at http://ctwc.weizmann.ac.il. SUPPLEMENTARY
      INFORMATION: The site has a link to an example which provides figures and
      detailed explanations

PMID- 12801878
TI  - RASCAL: rapid scanning and correction of multiple sequence alignments.
AB  - MOTIVATION: Most multiple sequence alignment programs use heuristics that
      sometimes introduce errors into the alignment. The most commonly used methods to
      correct these errors use iterative techniques to maximize an objective function.
      We present here an alternative, knowledge-based approach that combines a number
      of recently developed methods into a two-step refinement process. The alignment
      is divided horizontally and vertically to form a 'lattice' in which well aligned
      regions can be differentiated. Alignment correction is then restricted to the
      less reliable regions, leading to a more reliable and efficient refinement
      strategy. RESULTS: The accuracy and reliability of RASCAL is demonstrated using:
      (i) alignments from the BAliBASE benchmark database, where significant
      improvements were often observed, with no deterioration of the existing high
      quality regions, (ii) a large scale study involving 946 alignments from the
      ProDom protein domain database, where alignment quality was increased in 68% of
      the cases; and (iii) an automatic pipeline to obtain a high-quality alignment of
      695 full-length nuclear receptor proteins, which took 11 min on a DEC Alpha 6100
      computer AVAILABILITY: RASCAL is available at ftp://ftp-igbmc.u
      strasbg.fr/pub/RASCAL. SUPPLEMENTARY INFORMATION: http://bioinfo-igbmc.u
      strasbourg.fr/BioInfo/RASCAL/paper/rascal_supp.html

PMID- 12801879
TI  - The small-world dynamics of tree networks and data mining in phyloinformatics.
AB  - MOTIVATION: A noble and ultimate objective of phyloinformatic research is to
      assemble, synthesize, and explore the evolutionary history of life on earth. Data
      mining methods for performing these tasks are not yet well developed, but one
      avenue of research suggests that network connectivity dynamics will play an
      important role in future methods. Analysis of disordered networks, such as small
      world networks, has applications as diverse as disease propagation, collaborative
      networks, and power grids. Here we apply similar analyses to networks of
      phylogenetic trees in order to understand how synthetic information can emerge
      from a database of phylogenies. RESULTS: Analyses of tree network connectivity in
      TreeBASE show that a collection of phylogenetic trees behaves as a small-world
      network-while on the one hand the trees are clustered, like a non-random lattice,
      on the other hand they have short characteristic path lengths, like a random
      graph. Tree connectivities follow a dual-scale power-law distribution (first
      power-law exponent approximately 1.87; second approximately 4.82). This unusual
      pattern is due, in part, to the presence of alternative tree topologies that
      enter the database with each published study. As expected, small collections of
      trees decrease connectivity as new trees are added, while large collections of
      trees increase connectivity. However, the inflection point is surprisingly low:
      after about 600 trees the network suddenly jumps to a higher level of coherence.
      More stringent definitions of 'neighbour' greatly delay the threshold whence a
      database achieves sufficient maturity for a coherent network to emerge. However,
      more stringent definitions of 'neighbour' would also likely show improved focus
      in data mining. AVAILABILITY: http://treebase.org

PMID- 12801880
TI  - Modular modeling of cellular systems with ProMoT/Diva.
AB  - MOTIVATION: Need for software to setup and analyze complex mathematical models
      for cellular systems in a modular way, that also integrates the experimental
      environment of the cells. RESULTS: A computer framework is described which allows
      the building of modularly structured models using an abstract, modular and
      general modeling methodology. With this methodology, reusable modeling entities
      are introduced which lead to the development of a modeling library within the
      modeling tool ProMot. The simulation environment Diva is used for numerical
      analysis and parameter identification of the models. The simulation environment
      provides a number of tools and algorithms to simulate and analyze complex
      biochemical networks. The described tools are the first steps towards an
      integrated computer-based modeling, simulation and visualization environment
      Availability: Available on request to the authors. The software itself is free
      for scientific purposes but requires commercial libraries. SUPPLEMENTARY
      INFORMATION: http://www.mpi-magdeburg.mpg.de/projects/promot

PMID- 12801881
TI  - Genescript: DNA sequence annotation pipeline.
AB  - Genescript uses a number of publicly available analysis programs to annotate a
      DNA sequence. It provides an integrated display of results from each program, and
      includes an evidence-based scoring system that gives informative summaries of
      predicted gene models. AVAILABILITY: Genescript is available for download from
      http:://tcag.bioinfo.sickkids.on.ca/genescript/

PMID- 12801882
TI  - PAR-2 agonists induce contraction of murine small intestine through neurokinin
      receptors.
AB  - Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor and is
      expressed throughout the gut. It is well known that PAR-2 participates in the
      regulation of gastrointestinal motility; however, the results are inconsistent.
      The present study investigated the effect and mechanism of PAR-2 activation on
      murine small intestinal smooth muscle function in vitro. Both trypsin and PAR-2
      activating peptide SLIGRL induced a small relaxation followed by a concentration
      dependent contraction. The sensitivity to trypsin was greater than that to SLIGRL
      (EC50 = 0.03 vs. 40 microM), but maximal responses were similar (12.3 +/- 1.6 vs.
      13.7 +/- 1.3 N/cm2). Trypsin-evoked contraction (1 microM) exhibited a rapid
      desensitization, whereas the desensitization of response to SLIGRL was less even
      at high concentration (50 microM). Atropine had no effect on PAR-2 agonist
      induced contractions. In contrast, TTX and capsaicin significantly attenuated
      those contractions, implicating a neurogenic mechanism that may involve capsaicin
      sensitive sensory nerves. Furthermore, contractions induced by trypsin and SLIGRL
      were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR
      48968 alone or were further reduced by combined application of SR-140333 and SR
      48968, indicating the involvement of neurokinin receptors. In addition,
      desensitizing neurokinin receptors with substance P and/or neurokinin A decreased
      the PAR-2 agonist-evoked contraction. We concluded that PAR-2 agonists induced a
      contraction of murine intestinal smooth muscle that was mediated by nerves. The
      excitatory effect is also dependent on sensory neural pathways and requires both
      NK1 and NK2 receptors.

PMID- 12801883
TI  - Enhancement of antral contractions and vagal afferent signaling with synchronized
      electrical stimulation.
AB  - Gastric filling activates vagal afferents involved in peripheral signaling to the
      central nervous system (CNS) for food intake. It is not known whether these
      afferents linearly encode increasing contractions of the antrum during antral
      distension (AD). The aim of this study was to investigate effects of AD and
      electrically enhanced antral contractions on responses of vagal afferents
      innervating the antrum. Single-fiber recordings were made from the vagal
      afferents in anesthetized male Long-Evans rats. Antral contractions were measured
      with a solid-state probe placed in the antrum. A nonexcitatory electrical
      stimulation (NES) inducing no smooth muscle contractions was applied during the
      ascending phase of antral contractions to enhance subsequent antral contractions.
      Fifty-six fibers identified during AD (1 ml for 30 s) were studied through
      different types of mechanical stimuli. Under normal conditions, one group of
      fibers exhibited rhythmic firing in phase with antral contractions. Another group
      of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested
      with NES during multiple-step distension (MSD). NES produced a mean increase in
      antral contraction amplitude (177.1 +/- 35.3%) and vagal afferent firing (21.6 +/
      2.6%). Results show that both passive distension and enhanced antral
      contractions activate distension-sensitive vagal afferents. Responses of these
      fibers increase linearly to enhanced antral contraction induced by NES or MSD up
      to a distending volume of 0.6 ml. However, responses reached a plateau at a
      distending volume >0.8 ml. We concluded that enhanced contraction of the antrum
      can activate vagal afferents signaling to the CNS.

PMID- 12801884
TI  - CRHSP-24 phosphorylation is regulated by multiple signaling pathways in
      pancreatic acinar cells.
AB  - Ca2+-regulated heat-stable protein of 24 kDa (CRHSP-24) is a serine
      phosphoprotein originally identified as a physiological substrate for the Ca2+
      calmodulin regulated protein phosphatase calcineurin (PP2B). CRHSP-24 is a
      paralog of the brain-specific mRNA-binding protein PIPPin and was recently shown
      to interact with the STYX/dead phosphatase protein in developing spermatids
      (Wishart MJ and Dixon JE. Proc Natl Acad Sci USA 99: 2112-2117, 2002).
      Investigation of the effects of phorbol ester (12-o-tetradecanoylphorbol-13
      acetate; TPA) and cAMP analogs in 32P-labeled pancreatic acini revealed that
      these agents acutely dephosphorylated CRHSP-24 by a Ca2+-independent mechanism.
      Indeed, cAMP- and TPA-mediated dephosphorylation of CRHSP-24 was fully inhibited
      by the PP1/PP2A inhibitor calyculin A, indicating that the protein is regulated
      by an additional phosphatase other than PP2B. Supporting this, CRHSP-24
      dephosphorylation in response to the Ca2+-mobilizing hormone cholecystokinin was
      differentially inhibited by calyculin A and the PP2B-selective inhibitor
      cyclosporin A. Stimulation of acini with secretin, a secretagogue that signals
      through the cAMP pathway in acini, induced CRHSP-24 dephosphorylation in a
      concentration-dependent manner. Isoelectric focusing and immunoblotting indicated
      that elevated cellular Ca2+ dephosphorylated CRHSP-24 on at least three serine
      sites, whereas cAMP and TPA partially dephosphorylated the protein on at least
      two sites. The cAMP-mediated dephosphorylation of CRHSP-24 was inhibited by low
      concentrations of okadaic acid (10 nM) and fostriecin (1 microM), suggesting that
      CRHSP-24 is regulated by PP2A or PP4. Collectively, these data indicate that
      CRHSP-24 is regulated by diverse and physiologically relevant signaling pathways
      in acinar cells, including Ca2+, cAMP, and diacylglycerol.

PMID- 12801885
TI  - Differential mechanism and site of action of CCK on the pancreatic secretion and
      growth in rats.
AB  - Recent studies demonstrated that cholecystokinin (CCK) at physiological levels
      stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal
      pathway. This study examined whether chemical ablation of afferent vagal fibers
      influences pancreatic growth and secretion in rats. Bilateral subdiaphragmatic
      vagal trunks were exposed, and capsaicin solution was applied. Pancreatic wet
      weight and pancreatic secretion and growth in response to endogenous and
      exogenous CCK were examined 7 days after capsaicin treatment. Perivagal
      application of capsaicin increased plasma CCK levels and significantly increased
      pancreatic wet weight compared with those in the control rats. Oral
      administration of CCK-1 receptor antagonist loxiglumide prevented the increase in
      pancreatic wet weight after capsaicin treatment. In addition, continuous
      intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and
      pancreatic wet weight after capsaicin treatment. There were no significant
      differences in the expression levels of CCK-1 receptor mRNA and protein in the
      pancreas in capsaicin-treated and control rats. Intraduodenal administration of
      camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in
      control rats but not in capsaicin-treated rats. In contrast, repeated oral
      administrations of camostat or intraperitoneal injections of CCK-8 significantly
      increased pancreatic wet weight in both capsaicin-treated and control rats.
      Present results suggest that perivagal application of capsaicin stimulates
      pancreatic growth via an increase in endogenous CCK and that exogenous and
      endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but
      directly in rats.

PMID- 12801886
TI  - Toxin B of Clostridium difficile activates human VIP submucosal neurons, in part
      via an IL-1beta-dependent pathway.
AB  - This study investigated whether toxin B of Clostridium difficile can activate
      human submucosal neurons and the involved pathways. Isolated segments of human
      colon were placed in organ culture for 3 h in the presence of toxin B or IL
      1beta. Whole mounts of internal submucosal plexus were stained with antibodies
      against c-Fos, neuron-specific enolase (NSE), vasoactive intestinal polypeptide
      (VIP), and substance P (SP). The membrane potential (Vm) response of submucosal
      neurons to local application of toxin B and IL-1beta was determined by a
      multisite optical recording technique. Toxin B (0.1 to 10 ng/ml) increased the
      proportion of c-Fos-positive neurons dose dependently compared with the control.
      In the presence of toxin B (10 ng/ml), most c-Fos-positive neurons were
      immunoreactive for VIP (79.8 +/- 22.5%) but only 19.4 +/- 14.0% for SP. Toxin B
      induced a rapid rise in IL-1beta mRNA level and a sixfold increase in IL-1beta
      protein in supernatant after 3 h of incubation. c-Fos expression induced by toxin
      B was reduced dose dependently by IL-1 receptor antagonist (0.1-10 ng/ml). IL
      1beta significantly increased c-Fos expression in submucosal neurons compared
      with the control (34.2 +/- 10.1 vs. 5.1 +/- 1.3% of NSE neurons). Microejection
      of toxin B had no effect on the Vm of enteric neurons. Evidence of a direct
      excitatory effect of IL-1beta on Vm was detected in a minority of enteric
      neurons. Therefore, toxin B of C. difficile activates VIP-positive submucosal
      neurons, at least in part, via an indirect IL-1beta-dependent pathway.

PMID- 12801887
TI  - PG-mediated closure of paracellular pathway and not restitution is the primary
      determinant of barrier recovery in acutely injured porcine ileum.
AB  - Small bowel epithelium is at the frontline of intestinal barrier function.
      Restitution is considered to be the major determinant of epithelial repair,
      because function recovers in parallel with restitution after acute injury. As
      such, studies of intact mucosa have largely been replaced by migration assays of
      cultured epithelia. These latter studies fail to account for the simultaneous
      roles played by villous contraction and paracellular permeability in recovery of
      barrier function. NSAIDs result in increased intestinal permeability and disease
      exacerbation in patients with inflammatory bowel disease (IBD). Thus we examined
      the reparative attributes of endogenous PGs after injury of ileal mucosa by
      deoxycholate (6 mM) in Ussing chambers. Recovery of transepithelial electrical
      resistance (TER) from 20-40 Omega.cm2 was abolished by indomethacin (Indo),
      whereas restitution of 40-100% of the villous surface was unaffected despite
      concurrent arrest of villous contraction. In the presence of PG, resident crypt
      and migrating epithelial cells were tightly apposed. In tissues treated with
      Indo, crypt epithelial cells had dilated intercellular spaces that were
      accentuated in the migrating epithelium. TER was fully rescued from the effects
      of Indo by osmotic-driven collapse of the paracellular space, and PG-mediated
      recovery was significantly impaired by blockade of Cl- secretion. These studies
      are the first to clearly distinguish the relative contribution of paracellular
      resistance vs. restitution to acute recovery of epithelial barrier function.
      Restitution was ineffective in the absence of PG-mediated paracellular space
      closure. Failure of PG-mediated repair mechanisms may underlie barrier failure
      resulting from NSAID use in patients with underlying enteropathy.

PMID- 12801889
TI  - Functional role of the NPxxY motif in internalization of the type 2 vasopressin
      receptor in LLC-PK1 cells.
AB  - Interaction of the type 2 vasopressin receptor (V2R) with hormone causes
      desensitization and internalization. To study the role of the V2R NPxxY motif
      (which is involved in the clathrin-mediated endocytosis of several other
      receptors) in this process, we expressed FLAG-tagged wild-type V2R and a Y325F
      mutant V2R in LLC-PK1a epithelial cells that have low levels of endogenous V2R.
      Both proteins had a similar apical (35%) and basolateral (65%) membrane
      distribution. Substitution of Tyr325 with Phe325 prevented ligand-induced
      internalization of V2R determined by [3H]AVP binding and immunofluorescence but
      did not prevent ligand binding or signal transduction via adenylyl cyclase.
      Desensitization and resensitization of the V2R-Y325F mutation occurred
      independently of internalization. The involvement of clathrin in V2R
      downregulation was also shown by immunogold electron microscopy. We conclude that
      the NPxxY motif of the V2R is critically involved in receptor downregulation via
      clathrin-mediated internalization. However, this motif is not essential for the
      apical/basolateral sorting and polarized distribution of the V2R in LLC-PK1a
      cells or for adenylyl cyclase-mediated signal transduction.

PMID- 12801888
TI  - Phosphorylation of threonine 276 in Smad4 is involved in transforming growth
      factor-beta-induced nuclear accumulation.
AB  - Smad4, the common Smad, is central for transforming growth factor (TGF)-beta
      superfamily ligand signaling. Smad4 has been shown to be constitutively
      phosphorylated (Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A,
      Oeda E, Tamaki K, Hanai J, Heldin C-H, Miyazono K, and ten Dijke P. EMBO J 16:
      5353-5362, 1997), but the site(s) of phosphorylation, the kinase(s) that performs
      this phosphorylation, and the significance of the phosphorylation of Smad4 are
      currently unknown. This report describes the identification of a consensus ERK
      phosphorylation site in the linker region of Smad4 at Thr276. Our data show that
      ERK can phosphorylate Smad4 in vitro but not Smad4 with mutated Thr276. Flag
      tagged Smad4-T276A mutant protein accumulates less efficiently in the nucleus
      after stimulation by TGF-beta and is less efficient in generating a
      transcriptional response than Smad4 wild-type protein. Tryptic phosphopeptide
      mapping identified a phosphopeptide in Smad4 wild-type protein that was absent in
      phosphorylated Smad4-T276A mutant protein. Our results suggest that MAP kinase
      can phosphorylate Thr276 of Smad4 and that phosphorylation can lead to enhanced
      TGF-beta-induced nuclear accumulation and, as a consequence, enhanced
      transcriptional activity of Smad4.

PMID- 12801890
TI  - Presence of Ca2+-dependent K+ channels in chemosensory cilia support a role in
      odor transduction.
AB  - Olfactory receptor neurons (ORNs) respond to odorants with changes in the action
      potential firing rate. Excitatory responses, consisting of firing increases, are
      mediated by a cyclic AMP cascade that leads to the activation of cationic
      nonselective cyclic nucleotide-gated (CNG) channels and Ca2+-dependent Cl- (ClCa)
      channels. This process takes place in the olfactory cilia, where all protein
      components of this cascade are confined. ORNs from various vertebrate species
      have also been shown to generate inhibitory odor responses, expressed as
      decreases in action potential discharges. Odor inhibition appears to rely on Ca2+
      dependent K+ (KCa) channels, but the underlying transduction mechanism remains
      unknown. If these channels are involved in odor transduction, they are expected
      to be present in the olfactory cilia. We found that a specific antibody against a
      large conductance KCa recognized a protein of approximately 116 kDa in Western
      blots of purified rat olfactory ciliary membranes. Moreover, the antibody labeled
      ORN cilia in isolated ORNs from rat and toad (Caudiverbera caudiverbera). In
      addition, single-channel recordings from inside-out membrane patches excised from
      toad chemosensory cilia showed the presence of 4 different types of KCa channels,
      with unitary conductances of 210, 60, 12, and 29 and 60 pS, high K+-selectivity,
      and Ca2+ sensitivities in the low micromolar range. Our work demonstrates the
      presence of K+ channels in the ORN cilia and supports their participation in odor
      transduction.

PMID- 12801891
TI  - Biophysical properties and ionic signature of neuronal progenitors of the
      postnatal subventricular zone in situ.
AB  - Previous studies have reported the presence of neuronal progenitors in the
      subventricular zone (SVZ) and rostral migratory stream (RMS) of the postnatal
      mammalian brain. Although many studies have examined the survival and migration
      of progenitors after transplantation and the factors influencing their
      proliferation or differentiation, no information is available on the
      electrophysiological properties of these progenitors in a near-intact
      environment. Thus we performed whole cell and cell-attached patch-clamp
      recordings of progenitors in brain slices containing either the SVZ or the RMS
      from postnatal day 15 to day 25 mice. Both regions displayed strong
      immunoreactivity for nestin and neuron-specific class III beta-tubulin, and
      recorded cells displayed a morphology typical of the neuronal progenitors known
      to migrate throughout the SVZ and RMS to the olfactory bulb. Recorded progenitors
      had depolarized zero-current resting potentials (mean more depolarized than -28
      mV), very high input resistances (about 4 GOmega), and lacked action potentials.
      Using the reversal potential of K+ currents through a cell-attached patch a mean
      resting potential of -59 mV was estimated. Recorded progenitors displayed Ca2+
      dependent K+ currents and TEA-sensitive-delayed rectifying K+ (KDR) currents, but
      lacked inward K+ currents and transient outward K+ currents. KDR currents
      displayed classical kinetics and were also sensitive to 4-aminopyridine and alpha
      dendrotoxin, a blocker of Kv1 channels. Na+ currents were found in about 60% of
      the SVZ neuronal progenitors. No developmental changes were observed in the
      passive membrane properties and current profile of neuronal progenitors. Together
      these data suggest that SVZ neuronal progenitors display passive membrane
      properties and an ionic signature distinct from that of cultured SVZ neuronal
      progenitors and mature neurons.

PMID- 12801892
TI  - Somatosympathetic reflexes from the low back in the anesthetized cat.
AB  - In the appendicular skeleton, substantial evidence demonstrates that
      somatosensory input from deep tissues including limb muscles and joints elicits
      somatosympathetic reflexes. Much less is known about the presence and
      organization of these reflexes from the axial skeleton. We determined if
      mechanical loading of the lumbar spine and lumbar paraspinal muscle irritation
      reflexively affects postganglionic sympathetic nerve discharge (SND) to the
      spleen and kidney. In 27 alpha-chloralose-anesthetized cats, the L2-4 multifidus
      muscles were injected with the inflammatory irritant mustard oil (20%, 60 microl
      total) and a vertebral load (100% body weight) was applied dorsal-ventral at the
      L3 spinous process. Mustard oil injection alone without vertebral loading (n = 7)
      increased mean splenic SND (60%), renal SND (30%), and heart rate (HR; 52 bpm).
      Mustard oil injection accompanied by the vertebral load (n = 7) increased mean
      splenic SND (55%), renal SND (16%), and HR (27 bpm). Blood pressure changes were
      biphasic and could not account for these changes. When the vertebral load
      accompanied mustard oil, the increases in splenic SND, renal SND, and HR remained
      elevated in a pattern significantly different from when the vertebral load was
      absent. Vehicle injection combined with the mechanical load (n = 3) did not
      change any of the autonomic responses. Similarly, mustard oil injection combined
      with a mechanical load did not change these responses when either the medial
      branches of the dorsal rami from T11-L5 had been cut (n = 4) or when the spinal
      cord had been transected between the second and third cervical vertebrae (n = 6).
      The results indicate that inflammatory stimulation of multifidus muscle in the
      low back evokes a somatosympathetic reflex integrated supraspinally in the upper
      cervical spinal cord or higher. The reflex's afferent arm travels in the medial
      branch of the dorsal ramus, and its efferent arm can affect sympathetic outflow
      to the spleen and the kidney as well as HR and BP. A static mechanical load
      applied to the lumbar spine accompanying the inflammatory stimulus appears to
      sustain the inflammatory-induced reflex activity.

PMID- 12801893
TI  - Nonspatial saccade-specific activation in area LIP of monkey parietal cortex.
AB  - We present evidence that neurons in the lateral intraparietal area (LIP) of
      monkey posterior parietal cortex (PPC) are activated by the instruction to make
      an eye movement, even in the complete absence of a spatial target. This study
      employed a visually guided motor task that dissociated the type of movement to
      make (saccade or reach) from the location where the movement was to be made.
      Using this task, animals were instructed to prepare a specific type of movement
      prior to knowing the spatial location of the movement target. We found that 25%
      of the LIP neurons recorded in two animals were activated significantly more by
      the instruction to prepare a saccade than by the instruction to prepare a reach.
      This finding indicates that LIP is involved in more than merely spatial attention
      and provides further evidence for nonspatial effector-specific signal processing
      in the dorsal stream.

PMID- 12801894
TI  - Excitatory and inhibitory intensity tuning in auditory cortex: evidence for
      multiple inhibitory mechanisms.
AB  - The intensity tuning of excitatory and suppressive domain frequency response
      areas was investigated in 230 cat primary auditory cortical and 92 posterior
      auditory field neurons. Suppressive domains were explored using simultaneous 2
      tone stimulation with one tone at the best excitatory frequency. The intensity
      tuning of excitatory and suppressive domains was negatively correlated,
      supporting the hypothesis that inhibitory sidebands are related to excitatory
      domain intensity tuning. To further test this hypothesis, we compared the slopes
      of the edges of suppressive bands to the intensity tuning of excitatory domains.
      Edges of suppressive bands next to excitatory domains had slopes significantly
      more slanted toward the excitatory area in neurons with intensity-tuned
      excitatory domains. This relationship was not observed for suppressive band edges
      not next to the excitatory domain (e.g., the lower edge of lower suppressive
      bands). This indicates that intensity tuning ultimately observed in the
      excitatory domain results from overlapping excitatory and inhibitory inputs. In
      combination with results using forward masking, our results suggest that there
      are separate early and late sources of inhibition contributing to cortical
      frequency response areas, and only the early-stage inhibition contributes to
      excitatory domain intensity tuning.

PMID- 12801895
TI  - Relating network synaptic connectivity and network activity in the lobster
      (Panulirus interruptus) pyloric network.
AB  - The lobster pyloric network has a densely interconnected synaptic connectivity
      pattern, and the role individual synapses play in generating network activity is
      consequently difficult to discern. We examined this issue by quantifying the
      effect on pyloric network phasing and spiking activity of removing the Lateral
      Pyloric (LP) and Ventricular Dilator (VD) neurons, which synapse onto almost all
      pyloric neurons. A confounding factor in this work is that LP and VD neuron
      removal alters pyloric cycle period. To determine the effects of LP and VD neuron
      removal on pyloric activity independent of these period alterations, we altered
      network period by current injection into a pyloric pacemaker neuron,
      hyperpolarized the LP or VD neuron to functionally remove each from the network,
      and plotted various measures of pyloric neuron activity against period with and
      without the LP or VD neuron. In normal physiological saline, in many (or most)
      cases removing either neuron had surprisingly little effect on the activity of
      its postsynaptic partners, which suggests that under these conditions these
      neurons play a relatively small role in determining pyloric activity. In the
      cases in which removal did alter postsynaptic activity, the effects were
      inconsistent across preparations, which suggests that either despite producing
      very similar neural outputs, pyloric networks from different animals have
      different cellular and synaptic properties, or some synapses contribute to
      network activity only under certain modulatory conditions, and the "baseline"
      level of modulatory influence the network receives from higher centers varies
      from animal to animal.

PMID- 12801896
TI  - Defensive movements evoked by air puff in monkeys.
AB  - Electrical stimulation of two connected cortical areas in the monkey brain, the
      ventral intraparietal area (VIP) in the intraparietal sulcus and the polysensory
      zone (PZ) in the precentral gyrus, evokes a specific set of movements. In one
      interpretation, these movements correspond to those typically used to defend the
      body from objects that are near, approaching, or touching the skin. The present
      study examined the movements evoked by a puff of air aimed at various locations
      on the face and body of fascicularis monkeys to compare them to the movements
      evoked by stimulation of VIP and PZ. The air-puff-evoked movements included a
      movement of the eyes from any initial position toward a central region and a
      variety of stereotyped facial, shoulder, head, and arm movements. These movements
      were similar to those reported on stimulation of VIP and PZ. One difference
      between the air-puff-evoked movements and those evoked by stimulation of VIP and
      PZ is that the air puff evoked an initial startle response (a bilaterally
      symmetric spike in muscle activity) followed by a more sustained, lateralized
      response, specific to the site of the air puff. In contrast, stimulation of VIP
      and PZ evoked mainly a sustained, lateralized response, specific to the site of
      the receptive fields of the stimulated neurons. We speculate that VIP and PZ may
      contribute to the control of defensive movements, but that they may emphasize the
      more spatially specific reactions that occur after startle.

PMID- 12801897
TI  - Depolarization block of neurons during maintenance of electrographic seizures.
AB  - Epileptic seizures are associated with neuronal hyperactivity. Here, however, we
      investigated whether continuous neuronal firing is necessary to maintain
      electrographic seizures. We studied a class of "low-Ca2+" ictal epileptiform
      bursts, induced in rat hippocampal slices, that are characterized by prolonged (2
      15 s) interruptions in population spike generation. We found that, during these
      interruptions, neuronal firing was suppressed rather than desynchronized.
      Intracellular current injection, application of extracellular uniform electric
      fields, and antidromic stimulation showed that the source of action potential
      disruption was depolarization block. The duration of the extracellular potassium
      transients associated with each ictal burst was not affected by disruptions in
      neuronal firing. Application of phenytoin or veratridine indicated a critical
      role for the persistent sodium current in maintaining depolarization block. Our
      results show that continuous neuronal firing is not necessary for the maintenance
      of experimental electrographic seizures.

PMID- 12801898
TI  - Stimulus specificity and temporal dynamics of working memory for visual motion.
AB  - When asked to compare two moving stimuli separated by a delay, observers must not
      only identify stimulus direction but also store it in memory. We examined the
      properties of this storage mechanism in two macaque monkeys by sequentially
      presenting two random-dot stimuli, sample and test, in opposite hemifields and
      introducing a random-motion mask during the delay. The mask interfered with
      performance only at the precise location of the test, 100-200 ms after the start
      of the delay, and when its size and speed matched those of the remembered sample.
      This selective interference suggests that the representation of the motion
      stimulus in memory preserves its direction, speed, and size and is most fragile
      shortly after the completion of the encoding phase of the task. This precise
      preservation of sensory attributes of the motion stimulus suggests that the
      neural mechanisms involved in the processing of visual motion may also be
      involved in its storage.

PMID- 12801899
TI  - Protracted development of responses to whisker deflection in rat trigeminal
      ganglion neurons.
AB  - The rodent whisker-to-barrel pathway constitutes a major model system for
      studying experience-dependent brain development. Yet little is known about
      responses of neurons to whisker stimulation in young animals. Response properties
      of trigeminal ganglion (NV) neurons in 2-, 3-, and 4-week-old and adult rats were
      examined using extracellular single-unit recordings and controlled whisker
      stimuli. We found that the receptive field size of NV neurons is mature in 2-week
      old animals while response latencies, magnitudes, and angular tuning continue to
      develop between 2 weeks of age and adulthood. At the earliest time recorded, NV
      neurons respond to stimulation of only one whisker and can be characterized as
      slowly or rapidly adapting (SA, RA). The proportion of SA and RA neurons remains
      constant during development. Consistent with known on-going myelination of NV
      axons, response latencies decrease with age, becoming adult-like during the third
      and fourth postnatal weeks for RA and SA neurons, respectively. Unexpectedly, we
      found that evoked response magnitudes increase several-fold during development
      becoming adult-like only during the fourth postnatal week. In addition, RA
      neurons become less selective for whisker deflection angle with age. Maturation
      of response magnitude and angular tuning is consistent with developmental changes
      in the mechanical properties of the whisker, the whisker follicle, and the
      surrounding tissues. The findings indicate that whisker-derived tactile inputs
      mature during the first postnatal month when whisker-related cortical circuits
      are susceptible to long-term modification by sensory experience. Thus normal
      developmental changes in sensory input may influence functional development of
      cortical circuits.

PMID- 12801900
TI  - Recruitment order of cat abducens motoneurons and internuclear neurons.
AB  - Abducens neurons undergo a dose-dependent synaptic blockade (either disinhibition
      or complete blockade) when tetanus neurotoxin (TeNT) is injected into the lateral
      rectus muscle at either a low (0.5) or a high dose (5 ng/kg). We studied the
      firing pattern and recruitment order in abducens neurons both in control and
      after TeNT injection. The eye position threshold for recruitment of control
      abducens neurons was exponentially related to the eye position and velocity
      sensitivities. We also found a constancy of recruitment threshold for different
      eye movement modalities (spontaneous, optokinetic, and vestibular). Exponential
      relationships were found, as well, for eye velocity sensitivity during saccades
      and for position and velocity sensitivities during the vestibulo-ocular reflex.
      Likewise, inverse relationships were found between recruitment threshold or
      position sensitivity with the antidromic latency in control abducens neurons.
      These relationships, however, did not apply following TeNT treatment. Neuronal
      firing after TeNT appeared either disinhibited (low dose) or depressed (high
      dose), but the relationships between neuronal sensitivities and recruitment still
      applied. However, the pattern of recruitment shifted toward the treated side as
      more inputs were blocked by the low- and high-dose treatments, respectively.
      Nonetheless, although the recruitment-to-sensitivity relationships persisted
      under the TeNT synaptic blockade, we conclude that synaptic inputs are
      determinant for establishing the recruitment threshold and recruitment spacing of
      abducens motoneurons and internuclear neurons.

PMID- 12801901
TI  - Psychophysical investigation of an auditory spatial illusion in cats: the
      precedence effect.
AB  - The precedence effect (PE) describes several spatial perceptual phenomena that
      occur when similar sounds are presented from two different locations and
      separated by a delay. The mechanisms that produce the effect are thought to be
      responsible for the ability to localize sounds in reverberant environments.
      Although the physiological bases for the PE have been studied, little is known
      about how these sounds are localized by species other than humans. Here we used
      the search coil technique to measure the eye positions of cats trained to saccade
      to the apparent locations of sounds. To study the PE, brief broadband stimuli
      were presented from two locations, with a delay between their onsets; the delayed
      sound meant to simulate a single reflection. Although the cats accurately
      localized single sources, the apparent locations of the paired sources depended
      on the delay. First, the cats exhibited summing localization, the perception of a
      "phantom" sound located between the sources, for delays < +/-400 micros for
      sources positioned in azimuth along the horizontal plane, but not for sources
      positioned in elevation along the sagittal plane. Second, consistent with
      localization dominance, for delays from 400 micros to about 10 ms, the cats
      oriented toward the leading source location only, with little influence of the
      lagging source, both for horizontally and vertically placed sources. Finally, the
      echo threshold was reached for delays >10 ms, where the cats first began to
      orient to the lagging source on some trials. These data reveal that cats
      experience the PE phenomena similarly to humans.

PMID- 12801902
TI  - Hyperpolarization-activated current Ih disconnects somatic and dendritic spike
      initiation zones in layer V pyramidal neurons.
AB  - Layer V pyramidal cells of the somatosensory cortex operate with two spike
      initiation zones. Subthreshold depolarizations are strongly attenuated along the
      apical dendrite linking the somatic and distal dendritic spike initiation zones.
      Sodium action potentials, on the other hand, are actively back-propagating from
      the axon hillock into the apical tuft. There they can interact with local
      excitatory input leading to the generation of calcium action potentials. We
      investigated if and how back-propagating sodium action potentials alone, without
      concomitant excitatory dendritic input, can initiate calcium action potentials in
      the distal dendrite. In acute slices of the rat somatosensory cortex, layer V
      pyramidal cells were studied under current-clamp with simultaneous recordings
      from the soma and the apical dendrite. A train of four somatic action potentials
      had to reach high frequencies to induce calcium action potentials in the dendrite
      ("critical frequency," CF approximately 100 Hz). Depolarization in the dendrite
      reduced the CF, while hyperpolarization increased it. The CF depended on the
      presence of the hyperpolarization-activated current Ih: blockade with 20 microM 4
      (N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)
      reduced the CF to 68% of control. If the neurons were stimulated with noisy
      current injections, leading to in-vivo-like irregular spiking, no calcium action
      potentials were induced in the dendrite. However, after Ih channel blockade,
      calcium action potentials were frequently seen. These data suggest that Ih
      prevents initiation of the dendritic calcium action potential by proximal input
      alone. Dendritic calcium action potentials may therefore represent a unique
      signature for coincident somatic and dendritic activation.

PMID- 12801903
TI  - Distribution and function of GABAB receptors in spider peripheral
      mechanosensilla.
AB  - The mechanosensilla in spider exoskeleton are innervated by bipolar neurons with
      their cell bodies close to the cuticle and dendrites attached to it. Numerous
      efferent fibers synapse with peripheral parts of the mechanosensory neurons, with
      glial cells surrounding the neurons, and with each other. Most of these efferent
      fibers are immunoreactive to gamma-aminobutyric acid (GABA), and the sensory
      neurons respond to agonists of ionotropic GABA receptors with a rapid and
      complete inhibition. In contrast, little is known about metabotropic GABAB
      receptors that may mediate long-term effects. We investigated the distribution of
      GABAB receptors on spider leg mechanosensilla using specific antibodies against 2
      proteins needed to form functional receptors and an antibody that labels the
      synaptic vesicles on presynaptic sites. Both anti-GABAB receptor antibodies
      labeled the distal parts of the sensory cell bodies and dendrites but anti
      GABABR1 immunoreactivity was also found in the axons and proximal parts of the
      cell bodies and some glial cells. The fine efferent fibers that branch on top of
      the sensory neurons did not show GABAB receptor immunoreactivity but were densely
      labeled with anti-synapsin and indicated synaptic vesicles on presynaptic
      locations to the GABAB receptors. Intracellular recordings from sensory neurons
      innervating the slit sensilla of the spider legs revealed that application of
      GABAB receptor agonists attenuated voltage-activated Ca2+ current and enhanced
      voltage-activated outward K+ current, providing 2 possible mechanisms for
      controlling the neurons' excitability. These findings support the hypothesis that
      GABAB receptors are present in the spider mechanosensilla where their activation
      may modulate information transmission.

PMID- 12801904
TI  - A newly identified buccal interneuron initiates and modulates feeding motor
      programs in aplysia.
AB  - Despite considerable progress in characterizing the feeding central pattern
      generator (CPG) in Aplysia, the full complement of neurons that generate feeding
      motor programs has not yet been identified. The distribution of neuropeptide
      containing neurons in the buccal and cerebral ganglia can be used as a tool to
      identify additional elements of the feeding circuitry by providing distinctions
      between otherwise morphologically indistinct neurons. For example, our recent
      study revealed a unique and potentially interesting unpaired PRQFVamide (PRQFVa)
      containing neuron in the buccal ganglion. In this study, we describe the
      morphological and electrophysiological characterization of this novel neuron,
      which we designate as B50. We found that activation of B50 is capable of
      producing organized rhythmic output of the feeding CPG. The motor programs
      elicited by B50 exhibit some similarities as well as differences to motor
      programs elicited by the command-like cerebral-to-buccal interneuron CBI-2. In
      addition to activating the feeding CPG, B50 may act as a program modulator.

PMID- 12801905
TI  - Impact of expected reward on neuronal activity in prefrontal cortex, frontal and
      supplementary eye fields and premotor cortex.
AB  - In several regions of the macaque brain, neurons fire during delayed response
      tasks at a rate determined by the value of the reward expected at the end of the
      trial. The activity of these neurons might be related either to the internal
      representation of the appetitive value of the expected reward or to motivation
      dependent variations in the monkey's level of motor preparation or motor output.
      According to the first interpretation, reward-related activity should be most
      prominent in areas affiliated with the limbic system. According to the second
      interpretation, it should be most prominent in areas affiliated with the motor
      system. To distinguish between these alternatives, we carried out single-neuron
      recording while monkeys performed a memory-guided saccade task in which a visual
      cue presented early in each trial indicated whether the reward would be large or
      small. Neuronal activity accompanying task performance was monitored in the
      dorsolateral prefrontal cortex (PFC), the frontal eye field (FEF), a transitional
      zone caudal to the frontal eye field (FEF/PM), premotor cortex (PM), the
      supplementary eye field (SEF), and the rostral part of the supplementary motor
      area (SMAr). The tendency for neuronal activity to increase after cues that
      predicted a large reward became progressively stronger in progressively more
      posterior areas both in the lateral sector of the frontal lobe (PFC < FEF <
      FEF/PM < PM) and in the medial sector (SEF < SMAr). The very strong reward
      related activity of premotor neurons was presumably attributable to the monkey's
      motivation-dependent level of motor preparation or motor output. This finding
      points to the need to determine whether reward-related activity in other
      nonlimbic brain areas, including dorsolateral prefrontal cortex and the dorsal
      striatum, genuinely represents the value of the expected reward or,
      alternatively, is related to motivational modulation of motor signals.

PMID- 12801906
TI  - Production of mouse ES cells homozygous for Cdk5-phosphorylated site mutation in
      c-Src alleles.
AB  - c-Src-null mutants have not provided a full understanding of the cellular
      functions of c-Src, reflecting the functional redundancy among Src family
      members. c-Src is phosphorylated by cyclin-dependent kinase 1 (Cdk1) and Cdk5 at
      Ser75 in the unique amino terminal c-Src-specific domain. The specific roles of c
      Src may be assessed by establishing mouse embryonic stem (ES) cells homozygous
      for a point mutation at Ser75. Mammalian homozygous cultured cells with a point
      mutation, however, have not yet been produced by gene targeting. Here we show an
      efficient procedure for producing ES cell clones bearing a homozygous Ser75 to
      Asp mutation in the c-src gene. This procedure was developed by combining two
      previously reported strategies: our procedure for introducing a point mutation
      into one allele with no exogenous sequence, and the high-geneticin (G418)
      selection procedure for introducing a mutation into both alleles. The mutant
      clones expressed the same levels of c-Src protein and autophosphorylation
      activity as wild-type cells, but the mutant c-Src was not phosphorylated on Ser75
      during mitosis. This procedure is feasible for generating cells homozygous for a
      subtle mutation in most genes, and is expected to be applicable to other somatic
      cell lines.

PMID- 12801907
TI  - Inhibitory effects of green tea catechins on the activity of human matrix
      metalloproteinase 7 (matrilysin).
AB  - Inhibitory effects of green tea catechins and their derivatives on the matrilysin
      catalyzed hydrolysis of a synthetic substrate, (7-methoxycoumarin-4-yl)acetyl-L
      Pro-L-Leu-Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl]-L-Ala-L
      Arg-NH(2) [MOCAc-PLGL(Dpa)AR], were examined. The 10 catechins examined were
      classified into three groups according to their inhibition potency. Catechins
      with a galloyl group at the 3 position, including a major component of green tea
      catechin, (-)-epigallo-3-catechin gallate [(-)-EGCG], were the most potent
      inhibitors and inhibited matrilysin in a non-competitive manner with K(i) values
      of 0.47-1.65 micro M. The inhibitory potency of (-)-EGCG was not influenced by
      the presence of an inhibitor, ZnCl(2), suggesting that the inhibitions of
      matrilysin by (-)-EGCG and by ZnCl(2) might be independent of each other. The
      inhibitory effects of green tea catechins suggest that a high intake of green tea
      might be effective for the prevention of tumor metastasis and invasion in which
      matrilysin is concerned.

PMID- 12801908
TI  - Production of a functional catalytic antibody ScFv-NusA fusion protein in
      bacterial cytoplasm.
AB  - Functional expression of catalytic antibodies in the cytoplasm of E. coli is
      potentially of great interest in searching for new catalysts by genetic
      selection. Herein, a catalytic antibody single chain Fv (ScFv) 14D9, which
      catalyzes a highly enantioselective protonation, was expressed as a NusA fusion
      protein under the T7 promoter. A functional disulfide-containing ScFv fusion
      protein was obtained in the oxidizing environment of bacterial cytoplasm. The
      14D9 ScFv could not be overexpressed alone without NusA fusion. The highly
      soluble NusA protein most likely retards aggregate formation of ScFv and
      indirectly supports correct folding and disulfide bridge formation in the fusion
      construct ScFv-NusA. The ScFv-NusA fusion product shows highly enantioselective,
      specific, hapten inhibited catalytic activity comparable to its parent monoclonal
      antibody, 14D9. The NusA fusion method might be generally helpful for functional
      antibody expression in vivo and for the new development of biocatalysts by
      genetic selection.

PMID- 12801909
TI  - Critical enhancer region to which AhR/ARNT and Sp1 bind in the human CYP1B1 gene.
AB  - Cytochrome P450 (CYP) 1B1 is known to be induced by polycyclic aromatic
      hydrocarbons including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The
      constitutive and TCDD-inducible transcriptional expression of human CYP1B1 is
      known to be cell-specific. In order to identify the cis-elements that cell
      specifically regulate the constitutive and TCDD-inducible transcription of
      CYP1B1, we constructed luciferase reporter plasmids containing a series of
      deletions of the XRE core sequence in the 5'-flanking region of the human CYP1B1
      gene. Luciferase assays were performed with MCF-7 (breast carcinoma), HepG2
      (hepatocellular carcinoma), LS-180 (colon carcinoma), and OMC-3 (ovarian
      carcinoma) cells. Although there were large differences in the relative
      luciferase activity and inducibility between these four cell lines, the
      contribution of each reporter construct was similar. Constitutive expression
      increased with the regulatory elements that are present at -910 to -852 and -1652
      to -1243. Potential enhancer elements for TCDD-induction were located from -1022
      to -852 including three XREs, XRE3 at -853, XRE4 at -940, and XRE5 at -989. Gel
      shift analyses revealed binding of the AhR/ARNT heterodimer to XRE2 at -834, XRE3
      at -853, XRE6 at -1024, and XRE7 at -1490. In addition, the binding of a nuclear
      transcriptional factor, Sp1, near XRE2 and XRE8 was observed. It was suggested
      that mutual interaction of XRE2 and XRE3 is important for transcriptional
      regulation, and that the Sp1 binding to the Sp1-like motif (-824) enhances both
      the constitutive and inducible transcriptional activities of the human CYP1B1
      gene.

PMID- 12801910
TI  - pH- and salt-dependent self-assembly of human Rad51 protein analyzed as
      fluorescence resonance energy transfer between labeled proteins.
AB  - Human HsRad51 protein assembles on a DNA molecule through cooperative binding and
      forms a long filament for homologous recombination. We have characterized the
      self-assembly of HsRad51 by measuring the fluorescence resonance energy transfer
      from the fluorescein-labeled protein to the rhodamine-labeled protein. Self
      assembly quickly reached equilibrium and can be described by the head-to-tail
      polymerization of monomers, like that of its procaryotic homologue, RecA. It
      depended strongly on pH and was inhibited by high salt concentrations, indicating
      that ionic interactions between negatively and positively charged aminoacid
      residues are important. By contrast, neither ATP nor ADP significantly affected
      the reaction.

PMID- 12801912
TI  - Molecular cloning of a cDNA for the human phospholysine phosphohistidine
      inorganic pyrophosphate phosphatase.
AB  - We previously reported the isolation from bovine liver of a novel 56-kDa
      inorganic pyrophosphatase named phospholysine phosphohistidine inorganic
      pyrophosphate phosphatase (LHPPase). It is a unique enzyme that hydrolyzes not
      only oxygen-phosphorus bonds in inorganic pyrophosphate but also nitrogen
      phosphorus bonds in phospholysine, phosphohistidine and imidodiphosphate in
      vitro. In this study, we determined the partial amino acid sequence of the
      purified bovine LHPPase. To investigate whether humans have the same enzyme, we
      isolated a cDNA clone from a HeLa cell cDNA library that encodes for the human
      homologue of LHPPase. Although its sequence does not include the consensus
      sequence of a typical inorganic pyrophosphatase, it does contain a similar
      sequence of the active site in other phosphatases such as protein-tyrosine
      phosphatase, dual-specific phosphatase and low molecular weight acid phosphatase.
      Human LHPPase was highly expressed in the liver and kidney, and moderately in the
      brain. The recombinant protein was produced in E. coli. Its ability to hydrolyze
      oxygen-phosphorus bonds and nitrogen-phosphorus bonds was confirmed. The
      enzymatic characteristics of this human protein were similar to those of purified
      bovine LHPPase. Thus, we concluded that the cDNA encoded the human counterpart of
      bovine LHPPase.

PMID- 12801911
TI  - Regulation of ERK-mediated signal transduction by p38 MAP kinase in human
      monocytic THP-1 cells.
AB  - SB 203580 has been widely used to specifically shut down the p38 MAP kinase
      dependent pathway, although it is capable of inducing c-Raf kinase activity in
      cells. The present study demonstrates that SB 203580 activates members of the ERK
      cascade, c-Raf, MEK, and ERK, in human monocytic THP-1 cells. The activation of
      these kinases was sustained for at least 24 h after SB 203580 treatment and was
      also observed in U937 cells, suggesting that c-Raf efficiently transduces the
      signal even in the presence of the inhibitor in these cells. However, the
      expression of ERK cascade-dependent genes, such as c-fos and IL-1beta, was
      extremely limited. Analysis of the cellular distribution of ERK in SB 203580
      treated cells indicated that nuclear translocation of phosphorylated ERK was
      impaired. Also, nuclear translocation of ERK induced by 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) was inhibited by SB 239063, which does not associate
      with c-Raf and is highly selective for p38 MAP kinase. In addition, the forced
      expression of the dominant negative mutant of p38 MAP kinase suppressed serum
      responsive element-dependent transactivation induced by TPA. These results
      suggest that the steady-state level of p38 MAP kinase activity modulates ERK
      signaling.

PMID- 12801913
TI  - A novel rat orthologue and homologue for the Drosophila crooked neck gene in
      neural stem cells and their immediate descendants.
AB  - The crooked neck (crn) gene of Drosophila melanogaster encodes a scaffold protein
      carrying multiple tetratricopeptide repeat (TPR) motifs, and its mutation results
      in a reduction in the number of neuroblasts and lethality during larval stages.
      Here, we isolated two structurally related genes from a rat embryonic brain cDNA
      library. One gene is the rat orthologue of crn, which encodes 690 amino acids
      including 16 copies of TPR. The other gene, ATH55, encodes an 855 amino acid
      protein including 21 TPR motifs, which presumably represents a rat crn homologue
      and an orthologue of human XAB2. Both genes are highly expressed in embryonic
      brain but their expressions decrease during development. ATH55-like
      immunoreactivity is present in the ventricular zone and newly formed cortical
      plate, while CRN-like immunoreactivity is more abundant in a younger ventricular
      zone. In agreement, both proteins were found to be enriched in cultured neural
      stem cells and to decrease in response to cell differentiation signals. As
      indicated for the yeast CRN-like protein, ATH55 and CRN immunoreactivities were
      both recovered in the nuclear fraction and detected in the splicing complex
      carrying pre-mRNA. These findings suggest that both TPR-motif-containing proteins
      are involved in RNA processing of mammalian neural stem cells and their immediate
      descendants.

PMID- 12801914
TI  - Expression of Tom34 splicing isoforms in mouse testis and knockout of Tom34 in
      mice.
AB  - The 34-kDa translocase of the outer mitochondrial membrane (Tom34) is a putative
      mammalian-specific factor involved in protein import into mitochondria. We
      analyzed the genomic sequence of the mouse Tom34 gene and found it has two
      alternative initial exons. Using reverse transcription and the polymerase chain
      reaction (RT-PCR), we found that these two mRNAs differs only in the 5'-proximal
      sequences corresponding to the two initial exons (exon 1a and 1b). Tom34 mRNA
      with exon 1a (Tom34a) is expressed ubiquitously, while that with exon 1b (Tom34b)
      is expressed only in mature testicular germ cells. To explore the in vivo
      function of Tom34 proteins, we generated Tom34-deficient mice by targeted
      disruption. The Tom34(-/-) mice were viable and grew normally and had a normal
      Mendelian inheritance pattern. Male as well as female Tom34(-/-) mice were
      fertile. In vitro-preprotein import into isolated mitochondria showed no apparent
      difference between Tom34(-/-) and wild-type mice. These results indicate that
      Tom34 is dispensable for mouse growth and development under optimal conditions.

PMID- 12801915
TI  - Vascular endothelial growth factor principally acts as the main angiogenic factor
      in the early stage of human osteoblastogenesis.
AB  - Vascular endothelial growth factor (VEGF)-mediated angiogenesis is essential for
      bone formation. However, the effect of VEGF on osteoblastic cells during
      osteoblastogenesis is still controversial. The aim of this study was to clarify
      the relationship between osteoblastic cells derived from human mesenchymal stem
      cells (MSCs) and VEGF in the early stage of osteoblastic differentiation.
      Continuous dexamethasone treatment with a low concentration stimulated
      osteoblastogenesis of MSCs and the expression of VEGF121 mRNA. The VEGF secretion
      from osteoblastic cells also increased along with osteoblastogenesis. Neuropilin
      1, which mainly binds VEGF165, was detected at all stages during early
      osteoblastogenesis, but VEGF receptor-1 and -2 were not detected on RT-PCR
      analyses. In this study, VEGF had no direct effect on the proliferation of
      osteoblastic cells. However, the secreted VEGF in the conditioned medium of
      osteoblastic cells exhibited high angiogenic power as to endothelial cell
      proliferation. Our findings indicated that VEGF121 principally acts as the main
      angiogenic factor in the early stage of human osteoblastogenesis. The present
      study also demonstrated the differential expression of VEGF121 during
      osteoblastogenesis. The increase of VEGF in the early stage might be a useful
      marker of induction of bone formation due to human MSCs.

PMID- 12801916
TI  - Molecular cloning, expression, and characterization of a novel class of
      synaptotagmin (Syt XIV) conserved from Drosophila to humans.
AB  - Synaptotagmins (Syts) represent a large family of putative membrane trafficking
      proteins found in various species from different phyla. In this study, I
      identified a novel class of Syt (named Syt XIV) conserved from Drosophila to
      humans and its highly related molecule, Strep14 (Syt XIV-related protein).
      Although both Syt XIV and Strep14 belong to the C-terminal-type (C-type) tandem
      C2 protein family, only Syt XIV has a single transmembrane domain at the N
      terminus and a putative fatty-acylation site just downstream of the transmembrane
      domain. Biochemical analyses have indicated that Syt XIV is a Ca(2+)-independent
      Syt (e.g., Syts VIII, XII, and XIII) and that, like other Syt family proteins, it
      is capable of forming a Ca(2+)-independent oligomer. Unlike other Syt isoforms,
      however, expression of Syt XIV and Strep14 mRNA is highly restricted to mouse
      heart and testis and absent in the brain, where most other Syts are abundantly
      expressed, suggesting that Syt XIV and Strep14 may be involved in membrane
      trafficking in specific tissues outside the brain. I also identified all of the C
      type tandem C2 proteins in humans, the mouse, the fruit fly, a nematode, a plant,
      and a yeast and discuss the molecular evolution of the C-type tandem C2 protein
      families, including the Syt family, the Syt-like protein (Slp) family, and the
      Doc2 family.

PMID- 12801917
TI  - Purification and characterization of geranylgeranylglyceryl phosphate synthase
      from a thermoacidophilic archaeon, Thermoplasma acidophilum.
AB  - We purified a geranylgeranylglyceryl phosphate (GGGP) synthase from Thermoplasma
      acidophilum by several steps of chromatography. Based on the proteinase-fragment
      mass-pattern analysis of the SDS-PAGE band of the partially purified protein, the
      DNA sequence encoding the protein was identified from the whole genome sequence
      database of the species. The gene encoding GGGP synthase in T. acidophilum was
      cloned after PCR amplification of the gene from the genomic DNA. The recombinant
      enzyme was expressed in Escherichia coli and purified. A single band with a
      molecular mass of 27 kDa was obtained by SDS-PAGE analysis. The apparent native
      molecular mass of the enzyme was about 50 kDa based on gel filtration
      chromatography, suggesting that the enzyme is active as a homodimer. As the GGGP
      synthase from Methanobacterium thermoautotrophicum has been reported as a
      pentamer, the enzymes of the two organisms have different oligomeric structures.
      Other characteristics, including substrate specificity, are similar for the GGGPs
      of these organisms.

PMID- 12801918
TI  - Localization of calpain 3 in human skeletal muscle and its alteration in limb
      girdle muscular dystrophy 2A muscle.
AB  - Calpain 3/p94, the skeletal muscle-specific isoform of the calpain large subunit
      family, is a protein product of the gene responsible for limb-girdle muscular
      dystrophy type 2A (LGMD2A). Through yeast two-hybrid experiments, calpain 3 has
      been shown to bind to titin in myofibrils [Sorimachi et al. (1995) J. Biol. Chem.
      270, 31158-31162]. However, because of extensive autolysis activity, calpain 3
      localization in skeletal muscle has been undefined. In this study, we generated a
      polyclonal antibody against an N-terminal 98-amino-acid calpain 3 fragment, which
      is not homologous to the corresponding regions of other conventional calpains.
      This antibody stained myofibrils with a unique repeated doublet-pattern. Confocal
      microscopic observation with marker antibodies confirmed that calpain 3 is
      localized in the N2 region of myofibrils. Furthermore, using this antibody, we
      examined the localization of calpain 3 in LGMD2A muscles.

PMID- 12801919
TI  - The P5 activator of a group IC ribozyme can replace the P7.1/7.2 activator of a
      group IA ribozyme.
AB  - The P5 or P7 extensions in the group I intron ribozyme serve as "modular
      activator units" by stabilizing the conserved core of the ribozyme. The P5
      extension of a group IC1 intron was introduced to a barely active group IA2
      intron lacking its original P7 extension. The inserted P5 extension significantly
      activated the chimeric construct. Because the CYT-18 protein factor is also known
      to activate mutant group IA2 and IC1 introns lacking their P7 and P5 extensions,
      respectively, the RNA and protein activator units function in an analogous
      manner.

PMID- 12801920
TI  - Enzymological characterization of EpoA, a laccase-like phenol oxidase produced by
      Streptomyces griseus.
AB  - Laccase is an enzyme that catalyzes the oxidation of phenolic compounds by
      coupling the reduction of oxygen to water. While many laccases have been
      identified in plant and fungal species, enzymes of prokaryotic origin are poorly
      known. Here we report the enzymological characterization of EpoA, a laccase-like
      extracytoplasmic phenol oxidase produced by Streptomyces griseus. EpoA was
      expressed and purified with an Escherichia coli host-vector system as a
      recombinant protein fused with a C-terminal histidine-tag (rEpoA).
      Physicochemical analyses showed that rEpoA comprises a stable homotrimer
      containing all three types of copper (types 1-3). Various known laccase
      substrates were oxidized by rEpoA, while neither syringaldazine nor guaiacol
      served as substrates. Among the substrates examined, rEpoA most effectively
      oxidized N,N-dimethyl-p-phenylenediamine sulphate with a Km value of 0.42 mM.
      Several metal chelators caused marked inhibition of rEpoA activity, implying the
      presence of a metal center essential for the oxidase activity. The pH and
      temperature optima of rEpoA were 6.5 and 40 degrees C, respectively. The enzyme
      retained 40% activity after preincubation at 70 degrees C for 60 min. EpoA-like
      activities were detected in cell extracts of 8/40 environmental actinomycetes
      strains, which suggests that similar oxidases are widely distributed among this
      group of bacteria.

PMID- 12801921
TI  - The formation of the 7-carboxyheptyl radical from 13-hydroperoxy-9,11
      octadecadienoic acid catalyzed by hemoglobin and myoglobin under anaerobic
      conditions.
AB  - Methemoglobin (MetHb), oxyhemoglobin (oxyHb), metmyoglobin (metMb), and
      oxymyoglobin (oxyMb) catalyze formation of the 7-carboxyheptyl and pentyl
      radicals from 13-hydroperoxy-9,11-octadecadienoic acid. The relative HPLC-ESR
      peak height of the pentyl radical to the 7-carboxyheptyl radical was found to
      depend on the oxygen concentration in the reaction mixture. Under aerobic
      conditions, the 7-carboxyheptyl radical was predominant for the reaction mixture
      with ferrous ions (or cytochrome c, metHb, or metMb). On the other hand, under
      anaerobic conditions, the pentyl radical was predominant for the reaction mixture
      with ferrous ions (or cytochrome c), but the 7-carboxyheptyl radical was still
      predominant for the reaction mixture with metHb (or metMb), suggesting that metHb
      (or metMb) catalyzes the reaction through a mechanism different from that in the
      case of ferrous ions (or cytochrome c). In order to explain the above results, a
      mechanism, in which molecular oxygen is not involved, is proposed for the
      formation of the 7-carboxyheptyl radical in the reaction mixture of 13-HPODE with
      metHb (or metMb) under anaerobic conditions.

PMID- 12801922
TI  - Partial specific volume and adiabatic compressibility of G-actin depend on the
      bound nucleotide.
AB  - We determined the partial specific volume and partial specific adiabatic
      compressibility of either ATP- or ADP-bound monomeric actin in the presence of
      Ca(2+) by measuring the density of and sound velocity in a monomeric actin
      solution at 18 degrees C. The partial specific volume of ATP-bound monomeric
      actin, equal to 0.744 cm(3)/g, which is exceptionally high among globular
      proteins, was reduced to 0.727 cm(3)/g when the tightly bound ATP was replaced
      with ADP. Associated with this, the adiabatic compressibility of ATP-bound
      monomeric actin, equal to 8.8 x 10(-12) cm(2)/dyne, decreased to 5.8 x 10(-12)
      cm(2)/dyne, which is a common value for globular proteins. These results
      suggested that an extraordinarily soft global conformation of ATP-bound monomeric
      actin is packed into a compact mass associated with the hydrolysis of bound ATP.
      When monomeric actin was limitedly proteolyzed at subdomain 2 with subtilisin,
      the nucleotide-dependent flexibility of the global conformation of monomeric
      actin was lost.

PMID- 12801923
TI  - Neutralization of toxic heme by Plasmodium falciparum histidine-rich protein 2.
AB  - Plasmodium falciparum histidine-rich protein 2 (PfHRP2) has been suggested to be
      an initiator of the polymerization of heme, which is produced as by-product on
      the digestion of hemoglobin, and a promoter of the H(2)O(2)-induced degradation
      of heme in food vacuoles of the malarial parasite. In this work, we have designed
      PfHRP2 model peptides, R18 and R27 (18 and 27 residues, respectively), and used
      them for optical and electron spin resonance spectroscopic measurements to
      confirm that the axial ligands of the heme-PfHRP2 complex are the nitrogenous
      donors derived from the imidazole moieties of histidine residues of PfHRP2. In
      addition, we revealed that the affinities of R18 and R27 for heme (K(d) = 2.21 x
      10(-6) M and 0.71 x 10(-6) M, respectively) might be as high as that of PfHRP2
      (K(d) = 0.94 x 10(-6) M). The R27 peptide can remove heme from membrane
      intercalated heme and inhibit heme-induced hemolysis. Therefore, we suggest
      another function of PfHRP2: it may play an important role in the neutralization
      of toxic heme in the parasite cytoplasm and infected erythrocytes by removing
      heme from heme-bound membranes or reducing heme-induced hemolysis.

PMID- 12801924
TI  - The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc
      regulated zinc transporter in mice.
AB  - The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc
      metabolism acrodermatitis enteropathica. To understand its role in zinc
      homeostasis, we examined the function and expression of mouse ZIP4. This gene
      encodes a well conserved eight-transmembrane protein that can specifically
      increase the influx of zinc into transfected cells. Expression of this gene is
      robust in tissues involved in nutrient uptake, such as the intestines and
      embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc
      deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these
      tissues, whereas injection of zinc or increasing zinc content of the diet rapidly
      reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at
      the apical surface of enterocytes and visceral endoderm cells. These results
      provide compelling evidence that ZIP4 is a zinc transporter that plays an
      important role in zinc homeostasis, a process that is defective in acrodermatitis
      enteropathica in humans.

PMID- 12801925
TI  - On the role of the Escherichia coli RNA polymerase sigma 70 region 4.2 and alpha
      subunit C-terminal domains in promoter complex formation on the extended -10
      galP1 promoter.
AB  - Bacterial promoters of the extended -10 class contain a single consensus element,
      and the DNA sequence upstream of this element is not critical for promoter
      activity. Open promoter complexes can be formed on an extended -10 Escherichia
      coli galP1 promoter at temperatures as low as 6 degrees C, when complexes on most
      promoters are closed. Here, we studied the contribution of upstream contacts to
      promoter complex formation using galP1 and its derivatives lacking the extended 
      10 motif and/or containing the -35 promoter consensus element. A panel of E. coli
      RNA polymerase holoenzymes containing two, one, or no alpha-subunit C-terminal
      domains (alpha CTD) and either wild-type sigma 70 subunit or sigma 70 lacking
      region 4.2 was assembled and tested for promoter complex formation. At 37 degrees
      C, alpha CTD and sigma 70 region 4.2 were individually dispensable for promoter
      complex formation on galP1 derivatives with extended -10 motif. However, no
      promoter complexes formed when both alpha CTD and sigma 70 region 4.2 were
      absent. Thus, in the context of an extended -10 promoter, alpha CTD and sigma 70
      region 4.2 interactions with upstream DNA can functionally substitute for each
      other. In contrast, at low temperature, alpha CTD and sigma 70 region 4.2
      interactions with upstream DNA were found to be functionally distinct, for sigma
      70 region 4.2 but not alpha CTD was required for open promoter complex formation
      on galP1 derivatives with extended -10 motif. We propose a model involving sigma
      70 region 4.2 interaction with the beta flap domain that explains these
      observations.

PMID- 12801926
TI  - Role of the Reverse Transcriptase, Nucleocapsid Protein, and Template Structure
      in the Two-step Transfer Mechanism in Retroviral Recombination.
AB  - Template switching during reverse transcription promotes recombination in
      retroviruses. Efficient switches have been measured in vitro on hairpin
      containing RNA templates by a two-step mechanism. Pausing of the reverse
      transcriptase (RT) at the hairpin base allowed enhanced cleavage of the initial
      donor RNA template, exposing regions of the cDNA and allowing the acceptor to
      base pair with the cDNA. This defines the first or docking step. The primer
      continued synthesis on the donor, transferring or locking in a second step. Here
      we determine the enzyme-dependent factors that influence template switching by
      comparing the RTs from human immunodeficiency virus, type 1 (HIV-1), and equine
      infectious anemia virus (EIAV). HIV-1 RT promoted transfers with higher
      efficiency than EIAV RT. We found that both RTs paused strongly at the base of
      the hairpin. While stalled, HIV-1 RT made closely spaced cuts, whereas EIAV RT
      made only a single cut. Docking occurred efficiently at the multiply cut but not
      at the singly cut site. HIV-1 nucleocapsid (NC) protein stimulated strand
      transfers. It improved RNase H activity of both RTs. It allowed the EIAV RT to
      make a distribution of cuts, greatly stimulating docking at the base of the
      hairpin. Most likely, it also promoted strand exchange, allowing transfers to be
      initiated from sites throughout the hairpin. Minor pause sites beyond the base of
      the hairpin correlated with the locking sites. The strand exchange properties of
      NC likely promote this step. We present a model that explains the roles of RNase
      H specificity, template structure, and properties of NC in the two-step transfer
      reaction.

PMID- 12801927
TI  - Inhibition of interleukin-4-induced class switch recombination by a human
      immunoglobulin Fc gamma-Fc epsilon chimeric protein.
AB  - Immunoglobulin E (IgE) is important in mediating human allergic diseases. We
      tested the hypothesis that a human Ig Fc gamma-Fc epsilon bifunctional chimeric
      protein, GE2, would inhibit IgE class switch recombination (CSR) by co
      aggregating B-cell CD32 and CD23. Indeed, GE2 directly inhibited epsilon germ
      line transcription, subsequent CSR to epsilon and IgE protein production. This
      CSR inhibition was dependent on CD23 binding and the phosphorylation of
      extracellular signal-related kinase (ERK), and it was mediated via suppression of
      interleukin-4-induced STAT6 phosphorylation. Treatment with PD98059, a specific
      inhibitor of mitogen-activated protein kinase kinase 1 (MAPKK1 (MEK1)) and MEK2
      reversed the ability of GE2 to decrease CSR and STAT6 phosphorylation. GE2
      stimulation induced ERK phosphorylation, whereas it did not alter the
      phosphorylation of c-Jun N-terminal kinase or p38 MAPK. The ability of GE2 to
      block human isotype switching to epsilon, in addition to its already demonstrated
      ability to inhibit mast cell and basophil function, suggests that it will provide
      an important novel benefit in the treatment of IgE-mediated diseases.

PMID- 12801928
TI  - Regulation of Cdc25A half-life in interphase by cyclin-dependent kinase 2
      activity.
AB  - Cdc25A regulates cell cycle progression, has oncogenic and anti-apoptotic
      activity, and is over-expressed in many human tumors. Phosphorylation by Chk1 and
      Cds1/Chk2 down-regulates Cdc25A levels in response to genotoxic stresses.
      Nevertheless, it remains unclear whether Chk1 and Cds1/Chk2 are uniquely
      responsible for regulating Cdc25A stability during interphase or if other kinase
      activities contribute. Here we report that treatment of HeLa cells with the
      cyclin-dependent kinase inhibitor roscovitine caused a concentration- and time
      dependent increase in Cdc25A protein levels. Transfection with dominant-negative
      Cdk mutants demonstrated that only a Cdk2 mutant increased Cdc25A protein levels;
      Cdk1 and Cdk3 mutants had no effect. The increased Cdc25A protein levels were the
      result of an increase in the half-life of the protein; no increase in Cdc25A mRNA
      levels was observed. These results demonstrate Cdk2 kinase activity contributes
      to the labile nature of Cdc25A during interphase and redefine the nature of the
      Cdc25A-Cdk2 autoamplification feedback loop.

PMID- 12801929
TI  - Polyadenylation regulates the stability of Trypanosoma brucei mitochondrial RNAs.
AB  - Polyadenylation of RNAs plays a critical role in modulating rates of RNA turnover
      and ultimately in controlling gene expression in all systems examined to date. In
      mitochondria, the precise mechanisms by which RNAs are degraded, including the
      role of polyadenylation, are not well understood. Our previous in organello pulse
      chase experiments suggest that poly(A) tails stimulate degradation of mRNAs in
      the mitochondria of the protozoan parasite Trypanosoma brucei (Militello, K. T.,
      and Read, L. K. (2000) Mol. Cell. Biol. 21, 731-742). In this report, we
      developed an in vitro assay to directly examine the effects of specific 3'
      sequences on RNA degradation. We found that a salt-extracted mitochondrial
      membrane fraction preferentially degraded polyadenylated mitochondrially and non
      mitochondrially encoded RNAs over their non-adenylated counterparts. A poly(A)
      tail as short as 5 nucleotides was sufficient to stimulate rapid degradation,
      although an in vivo tail length of 20 adenosines supported the most rapid decay.
      A poly(U) extension did not promote rapid RNA degradation, and RNA turnover was
      slowed by the addition of uridine residues to the poly(A) tail. To stimulate
      degradation, the poly(A) element must be located at the 3' terminus of the RNA.
      Finally, we demonstrate that degradation of polyadenylated RNAs occurs in the 3'
      to 5' direction through the action of a hydrolytic exonuclease. These experiments
      demonstrate that the poly(A) tail can act as a cis-acting element to facilitate
      degradation of T. brucei mitochondrial mRNAs.

PMID- 12801930
TI  - Activation of human acid sphingomyelinase through modification or deletion of C
      terminal cysteine.
AB  - One form of Niemann-Pick disease is caused by a deficiency in the enzymatic
      activity of acid sphingomyelinase. During efforts to develop an enzyme
      replacement therapy based on a recombinant form of human acid sphingomyelinase
      (rhASM), purified preparations of the recombinant enzyme were found to have
      substantially increased specific activity if cell harvest media were stored for
      several weeks at -20 degrees C prior to purification. This increase in activity
      was found to correlate with the loss of the single free thiol on rhASM,
      suggesting the involvement of a cysteine residue. It was demonstrated that a
      variety of chemical modifications of the free cysteine on rhASM all result in
      substantial activation of the enzyme, and the modified cysteine responsible for
      this activation was shown to be the C-terminal residue (Cys629). Activation was
      also achieved by copper-promoted dimerization of rhASM (via cysteine) and by C
      terminal truncation using carboxypeptidase Y. The role of the C-terminal cysteine
      in activation was confirmed by creating mutant forms of rhASM in which this
      residue was either deleted or replaced by a serine, with both forms having
      substantially higher specific activity than wild-type rhASM. These results
      indicate that purified rhASM can be activated in vitro by loss of the free thiol
      on the C-terminal cysteine via chemical modification, dimerization, or deletion
      of this amino acid residue. This method of activation is similar to the cysteine
      switch mechanism described previously for matrix metalloproteinases and could
      represent a means of posttranslational regulation of ASM activity in vivo.

PMID- 12801931
TI  - Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in
      CD44-expressing tumor cells.
AB  - CD44 is an adhesion molecule that serves as a cell surface receptor for several
      extracellular matrix components, including hyaluronan (HA). The proteolytic
      cleavage of CD44 from the cell surface plays a critical role in the migration of
      tumor cells. Although this cleavage can be induced by certain stimuli such as
      phorbol ester and anti-CD44 antibodies in vitro, the physiological inducer of
      CD44 cleavage in vivo is unknown. Here, we demonstrate that HA oligosaccharides
      of a specific size range induce CD44 cleavage from tumor cells. Fragmented HA
      containing 6-mers to 14-mers enhanced CD44 cleavage dose-dependently by
      interacting with CD44, whereas a large polymer HA failed to enhance CD44
      cleavage, although it bound to CD44. Examination using uniformly sized HA
      oligosaccharides revealed that HAs smaller than 36 kDa significantly enhanced
      CD44 cleavage. In particular, the 6.9-kDa HA (36-mers) not only enhanced CD44
      cleavage but also promoted tumor cell motility, which was completely inhibited by
      an anti-CD44 monoclonal antibody. These results raise the possibility that small
      HA oligosaccharides, which are known to occur in various tumor tissues, promote
      tumor invasion by enhancing the tumor cell motility that may be driven by CD44
      cleavage.

PMID- 12801932
TI  - Antagonistic effects of beta-site amyloid precursor protein-cleaving enzymes 1
      and 2 on beta-amyloid peptide production in cells.
AB  - The deposition of extracellular beta-amyloid peptide (A beta) in the brain is a
      pathologic feature of Alzheimer's disease. The beta-site amyloid precursor
      protein cleaving enzyme 1 (BACE1), an integral membrane aspartyl protease
      responsible for cleavage of amyloid precursor protein (APP) at the beta-site,
      promotes A beta production. A second integral membrane aspartyl protease related
      to BACE1, referred to as beta-site amyloid precursor protein cleaving enzyme 2
      (BACE2) has also been demonstrated to cleave APP at the beta-cleavage site in
      transfected cells. The role of endogenous BACE2 in A beta production remains
      unresolved. We investigated the role of endogenous BACE2 in A beta production in
      cells by selective inactivation of its transcripts using RNA interference. We are
      able to reduce steady state levels for mRNA for each enzyme by >85%, and protein
      amounts by 88-94% in cells. Selective inactivation of BACE1 by RNA interference
      results in decreased beta-cleaved secreted APP and A beta peptide secretion from
      cells, as expected. Selective inactivation of BACE2 by RNAi results in increased
      beta-cleaved secreted APP and A beta peptide secretion from cells. Simultaneous
      targeting of both enzymes by RNA interference does not have any net effect on A
      beta released from cells. Our observations of changes in APP metabolism and A
      beta are consistent with a role of BACE2 in suppressing A beta production in
      cells that co-express both enzymes.

PMID- 12801933
TI  - The MEK/ERK pathway acts upstream of NF kappa B1 (p50) homodimer activity and Bcl
      2 expression in a murine B-cell lymphoma cell line. MEK inhibition restores
      radiation-induced apoptosis.
AB  - In a previously published report (Kurland, J. F., Kodym, R., Story, M. D.,
      Spurgers, K. B., McDonnell, T. J., and Meyn, R. E. (2001) J. Biol. Chem. 276,
      45380-45386), we described the NF kappa B status for two murine B-cell lymphoma
      cell lines, LY-as (apoptosis-sensitive) and LY-ar (apoptosis-refractory) and
      provided evidence that NF kappa B1 (p50) homodimers contribute to the expression
      of Bcl-2 in the LY-ar line. In the present study, we investigated the upstream
      signals leading to p50 homodimer activation and Bcl-2 expression. We found that
      in LY-ar cells, ERK1 and ERK2 were constitutively phosphorylated, whereas LY-as
      cells had no detectable ERK1 or ERK2 phosphorylation. Treatment of LY-ar cells
      with the MEK inhibitors PD 98059, U0126, and PD 184352 led to a loss of
      phosphorylated ERK1 and ERK2, a reversal of nuclear p50 homodimer DNA binding,
      and a decrease in Bcl-2 protein expression. Similarly, activation of the MEK/ERK
      pathway in LY-as cells by phorbol ester led to Bcl-2 expression that could be
      blocked by PD 98059. Furthermore, treatment of LY-ar cells with tumor necrosis
      factor-alpha, an I kappa B kinase activator, did not alter the suppressive effect
      of PD 98059 on p50 homodimer activity, suggesting an I kappa B kinase-independent
      pathway for p50 homodimer activation. Lastly, all three MEK inhibitors sensitized
      LY-ar cells to radiation-induced apoptosis. We conclude that the MEK/ERK pathway
      acts upstream of p50 homodimer activity and Bcl-2 expression in this B-cell
      lymphoma cell system and suggest that the use of MEK inhibitors could be useful
      clinically in combination with ionizing radiation to treat lymphoid malignancies.

PMID- 12801934
TI  - Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced
      tau protein phosphorylation.
AB  - The Alzheimer's disease pathogenic peptide, beta-amyloid42 (A beta 42), induces
      tau protein phosphorylation. Because hyperphosphorylated tau is a consistent
      component of neurofibrillary tangles, a pathological hallmark of Alzheimer's
      disease, we investigated the signaling molecules involved in A beta 42-induced
      tau phosphorylation. We show that A beta 42 elicited rapid and reversible tau
      protein phosphorylation on three proline-directed sites (Ser-202, Thr-181, and
      Thr-231) in systems enriched in alpha 7 nicotinic acetylcholine receptors (alpha
      7nAChR) including serum-deprived human SK-N-MC neuroblastoma cells and
      hippocampal synaptosomes. Although alpha 7nAChR agonists induced similar
      phosphorylation, pretreatment with antisense-alpha 7nAChR oligonucleotides (in
      cells) or alpha 7nAChR antagonists (in cells and synaptosomes) attenuated A beta
      induced tau phosphorylation. Western analyses showed that the mitogen-activated
      kinase cascade proteins, ERKs and c-Jun N-terminal kinase (JNK-1), were
      concomitantly activated by A beta 42, and their respective kinase inhibitors
      suppressed A beta-induced tau phosphorylation. More importantly, recombinant
      activated ERKs and JNK-1 could differentially phosphorylate tau protein in vitro.
      Thus, the alpha 7nAChR may mediate A beta-induced tau protein phosphorylation via
      ERKs and JNK-1.

PMID- 12801935
TI  - Novel mechanism of bacteriocin secretion and immunity carried out by lactococcal
      multidrug resistance proteins.
AB  - A natural isolate of Lactococcus lactis was shown to produce two narrow spectrum
      class II bacteriocins, designated LsbA and LsbB. The cognate genes are located on
      a 5.6-kb plasmid within a gene cluster specifying LmrB, an ATP-binding cassette
      type multidrug resistance transporter protein. LsbA is a hydrophobic peptide that
      is initially synthesized with an N-terminal extension. The housekeeping surface
      proteinase HtrA was shown to be responsible for the cleavage of precursor peptide
      to yield the active bacteriocin. LsbB is a relatively hydrophilic protein
      synthesized without an N-terminal leader sequence or signal peptide. The
      secretion of both polypeptides was shown to be mediated by LmrB. An L. lactis
      strain lacking plasmid-encoded LmrB and the chromosomally encoded LmrA is unable
      to secrete either of the two bacteriocins. Complementation of the strain with an
      active LmrB protein resulted in restored export of the two polypeptides across
      the cytoplasmic membrane. When expressed in an L. lactis strain that is sensitive
      to LsbA and LsbB, LmrB was shown to confer resistance toward both bacteriocins.
      It does so, most likely, by removing the two polypeptides from the cytoplasmic
      membrane. This is the first report in which a multidrug transporter protein is
      shown to be involved in both secretion and immunity of antimicrobial peptides.

PMID- 12801936
TI  - Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking
      Raf-1 interaction with Ras.
AB  - Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on
      serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). We show here
      that phosphorylation of all three sites blocks Raf-1 binding to Ras.GTP in vivo
      and that cAMP stimulates binding of 14-3-3 proteins to Ser233 and Ser259. We also
      show that Raf-1 and protein kinase A (PKA) form a complex in vivo that is
      disrupted by cAMP and that ablation of PKA by use of small interfering RNA blocks
      phosphorylation by cAMP. The ability of PKA to block Raf-1 activation is ablated
      by the PKA inhibitor H89. These studies suggest that Raf-1 and cAMP form a
      signaling complex in cells. Upon activation of PKA, Raf-1 is phosphorylated and
      14-3-3 binds, blocking Raf-1 recruitment to the plasma membrane and preventing
      its activation.

PMID- 12801937
TI  - European survey of vancomycin-resistant enterococci in at-risk hospital wards and
      in vitro susceptibility testing of ramoplanin against these isolates.
AB  - A survey in eight European countries, including 13 hospitals, of vancomycin
      resistant enterococci (VRE) in at-risk hospital wards (such as the ICU and the
      haematology ward) was performed in 2001, and the in vitro susceptibility of the
      isolates ramoplanin and other drugs was tested. A total of 1314 non-duplicate
      clinical enterococcal isolates were collected, and 38 (2.9%) were vancomycin
      resistant: 27 Enterococcus faecium and 11 Enterococcus faecalis; 35 VanA and
      three VanB phenotypes. Rates of VRE among clinical enterococcal isolates varied
      between 0 and 1.7% for the participating countries, except the UK (10.4%) and
      Italy (19.6%). One hundred and twenty-three (3.5%) VRE were found among 3499
      stool samples tested for the presence of these organisms: 111 (3.2%) E. faecium
      and 12 (0.3%) E. faecalis; 114 (3.3%) VanA and nine (0.3%) VanB phenotypes. Rates
      of intestinal colonization with VRE varied between 0 and 1.2% for the
      participating countries, except Italy (7.5%) and the UK (32.6%). In vitro
      susceptibility testing showed that the Italian and UK VRE are multi-resistant
      (including resistance to ampicillin and high-level resistance to gentamicin and
      streptomycin), and that ramoplanin was active against all strains of VRE, with an
      MIC90 of 0.5 mg/L for clinical isolates. Pulsed-field gel electrophoresis showed
      that the high prevalence of VRE in the Italian and UK centres was related to the
      monoclonal emergence and spread of three centre-specific clones. This survey
      suggests that in some centres in Europe, a similar situation may be encountered
      to that in the USA (monoclonal spread of multi-resistant VRE in at-risk wards).

PMID- 12801938
TI  - Clinical impact of vancomycin-resistant enterococci.
AB  - In humans, vancomycin-resistant enterococci (VRE) most commonly result in
      intestinal colonization, which does not result in symptoms, may persist for a
      long time and serves as a reservoir for transmission of VRE to other patients.
      Certain VRE-colonized patients are at risk of infection, including haematology
      and oncology patients, patients in intensive care units and recipients of solid
      (especially abdominal) organ transplants. Controlling the spread of VRE
      colonization and preventing colonized patients from becoming infected are
      important aims. Ramoplanin is a member of a new class of antimicrobial agents; it
      may have a role in preventing infection in patients colonized with VRE.

PMID- 12801939
TI  - Therapeutic and preventative options for the management of vancomycin-resistant
      enterococcal infections.
AB  - Enterococci are naturally resistant to a wide range of antimicrobial agents. In
      addition, some enterococci, known as vancomycin-resistant enterococci (VRE) have
      become resistant to glycopeptide antibiotics. The therapeutic options for VRE
      infections are therefore very limited. New antimicrobials have been developed
      that are active against VRE, such as linezolid and quinupristin/dalfopristin.
      Others, e.g. tigecycline, daptomycin and oritavancin, are in the later stages of
      development. However, resistance has already been detected to some of these
      agents. Some success has been enjoyed through the application of older
      antibiotics against VRE. The lack of therapeutic options has led to the
      consideration of measures to prevent infection with VRE. In addition to standard
      infection control procedures such as isolation and hand washing, decolonization
      of the gastrointestinal tract has been investigated as a method for the
      prevention of VRE infection in vulnerable patient groups. Several decolonization
      regimens have been investigated. These include the use of ramoplanin, a new
      glycolipodepsipeptide antibiotic that has features that particularly suit it for
      decolonization. Ramoplanin is not absorbed from the gastrointestinal tract, has
      potent bactericidal activity against Gram-positive organisms and limited side
      effects. These features and current clinical evidence suggest that ramoplanin may
      have a role in future gastrointestinal decolonization regimens.

PMID- 12801940
TI  - Ramoplanin: a novel antimicrobial agent with the potential to prevent vancomycin
      resistant enterococcal infection in high-risk patients.
AB  - The prevention of vancomycin-resistant Enterococcus (VRE) colonization and
      infection continues to be a high priority for clinicians. An oral antimicrobial
      agent that reduces or eliminates VRE gastrointestinal colonization could be
      useful for preventing VRE infection in selected patients. Ramoplanin, a
      glycolipodepsipeptide, is the first in a new class of antimicrobials. It has
      excellent in vitro activity against vancomycin-resistant Enterococcus faecium and
      Enterococcus faecalis. It is orally administered, and not absorbed systemically.
      In clinical trials, VRE gastrointestinal colonization was reduced to undetectable
      levels in 80-90% of patients during receipt of ramoplanin. A randomized, double
      blinded, placebo-controlled multicentre study is currently being conducted to
      determine whether ramoplanin will prevent VRE bloodstream infection in oncology
      patients who are neutropenic due to treatment for a haematological malignancy or
      a bone marrow/stem cell transplant.

PMID- 12801942
TI  - A change at the tiller.

PMID- 12801943
TI  - Gut and mind.
AB  - Obesity is a growing epidemic, causally associated with a number of serious
      medical conditions, including diabetes mellitus, coronary heart disease, and
      several cancers. The gut hormones ghrelin and peptide YY are secreted from the
      gut in response to changes to nutritional status. While food intake is stimulated
      by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology
      of ghrelin and peptide YY are discussed, focusing on the adaptive changes in
      diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important
      therapeutic targets in the quest to find an effective antiobesity treatment.

PMID- 12801944
TI  - A randomised prospective comparison of the Flamingo Wallstent and Ultraflex stent
      for palliation of dysphagia associated with lower third oesophageal carcinoma.
AB  - BACKGROUND: Covered metallic oesophageal stents offer effective palliation of
      malignant oesophageal strictures. However, first generation devices were
      associated with a high rate of migration, particularly when used in the lower
      oesophagus. AIM: To compare the rate of complications and palliative effect of
      two newer covered metallic oesophageal stents. PATIENTS AND METHODS: We performed
      a prospective randomised study using two of these newer stent designs in the
      treatment of malignant lower third oesophageal tumours. Fifty three patients with
      dysphagia due to inoperable oesophageal carcinoma involving the lower third of
      the oesophagus were randomly selected to receive either a Flamingo covered
      Wallstent (Boston Scientific Inc., Watertown, Massachusetts, USA) or an Ultraflex
      covered stent (Boston Scientific Inc.). Dysphagia was scored on a five point
      scale, recorded before stent insertion, the day after, and at least one month
      later at follow up. Technical success, early and late complications (perforation,
      migration, severe gastro-oesophageal reflux, haematemesis, and reobstruction due
      to tumour overgrowth) were also recorded. RESULTS: In both stent groups, a
      significant improvement in dysphagia score was seen both the next day post
      stenting and at late follow up (p<0.05). No significant difference was seen in
      the improvement in dysphagia between the two groups (p>0.1). The frequency of
      complications encountered in the two groups was similar. Three patients in the
      Ultraflex group required two stents at primary stenting. CONCLUSION: The two
      types of stent are equally effective in the palliation of dysphagia associated
      with lower third oesophageal malignancy and the complication rates associated
      with their use are comparable.

PMID- 12801945
TI  - Host gastric Lewis expression determines the bacterial density of Helicobacter
      pylori in babA2 genopositive infection.
AB  - BACKGROUND AND AIMS: We tested if host gastric Lewis antigens and the babA2
      genotype of Helicobacter pylori correlated with clinicohistological outcome.
      METHODS: We enrolled 188 dyspeptic patients (45 with duodenal ulcer, 45 with
      gastric ulcer, and 98 with chronic gastritis) with H pylori infection, proved by
      culture and gastric histology, reviewed by the updated Sydney system. Gastric
      expression of Lewis (Le) antigens Le(a), Le(b), Le(x), and Le(y) was determined
      immunochemically to determine intensity (range 0-3). The corresponding 188 H
      pylori isolates were screened for babA2 genotype by polymerase chain reaction.
      RESULTS: All H pylori isolates had a positive babA2 genotype. We identified Le(a)
      in 33.5%, Le(b) in 72.9%, Le(x) in 86.2%, and Le(y) in 97.4% of biopsies from
      these 188 patients. Patients who expressed Le(b) had a higher H pylori density
      than those who did not express Le(b) (p<0.001). Among 139 patients who expressed
      Le(b), H pylori density increased with a higher Le(b) intensity (p<0.05). Gastric
      atrophy decreased with Le(b) intensity and thus resulted in lower H pylori
      density in the antrum (p<0.05). For the 49 patients without gastric Le(b)
      expression, H pylori density was positively related with Le(x) and Le(a)
      expression (p<0.05). CONCLUSIONS: Taiwanese H pylori isolates are 100% babA2
      genopositive. Gastric Le(b) as well as Le(x) intensity may be major determinants
      of H pylori density. While lacking gastric Le(b) expression, Le(x) and Le(a) were
      closely related to H pylori colonisation.

PMID- 12801941
TI  - Guidelines for the investigation of chronic diarrhoea, 2nd edition.

PMID- 12801947
TI  - Risk of cancers of the oesophagus and stomach by histology or subsite in patients
      hospitalised for pernicious anaemia.
AB  - BACKGROUND: Although pernicious anaemia is an established risk factor for stomach
      cancer, data by anatomical subsite are not available. Moreover, a previous
      suggestion of a link to increased risk of oesophageal cancer needs further
      exploration. METHODS: We followed 21 265 patients hospitalised for pernicious
      anaemia in Sweden from 1965 to 1999 for an average of 7.1 years. Standardised
      incidence ratio (SIR) adjusted for sex, age, and calendar year was used to
      estimate relative risk, using the Swedish nationwide cancer incidence rates as
      reference. RESULTS: Significant excess risks for squamous cell carcinoma of the
      oesophagus, and stomach cancer distal to the cardia, were observed in pernicious
      anaemia patients (SIR 3.3 (95% confidence interval (CI) 2.4-4.4); SIR 2.4 (95% CI
      2.1-2.7), respectively). The excess risks increased with increasing follow up
      duration. Among distal stomach cancers, the most conspicuous excess risk was for
      carcinoid tumours (SIR 26.4 (95% CI 14.8-43.5)). Compared with the general
      population, no significant increased risk was observed for adenocarcinoma of the
      oesophagus (SIR 1.7 (95% CI 0.7-3.4)) or gastric cardia (SIR 1.2 (95%CI 0.6
      2.0)). CONCLUSIONS: Achlorhydria following type A atrophic gastritis is
      associated with an elevated risk of adenocarcinoma of the non-cardia stomach, and
      surprisingly, with a risk of oesophageal squamous cell carcinoma. In contrast, no
      significant association, either positive or negative, was found with oesophageal
      or cardia adenocarcinoma. The mechanism for the observed increased risk of
      oesophageal squamous cell carcinoma warrants further study.

PMID- 12801946
TI  - 13C urea breath test (UBT) in the diagnosis of Helicobacter pylori: why does it
      work better with acid test meals?
AB  - BACKGROUND: Acid test meals may improve the accuracy of the (13)C urea breath
      test (UBT). This has been attributed to changes in gastric emptying rather than
      to the effects of gastric pH on Helicobacter pylori urease. AIMS: To determine
      whether enhancement of (13)CO(2) excretion in the UBT in H pylori infected
      volunteers by acidification of a test meal is due to a delay in gastric emptying.
      METHODS: Urease activity in vitro was measured in intact bacteria and in
      bacterial homogenates. Urease activity in vivo was assessed by means of the UBT.
      Eleven H pylori infected subjects underwent UBTs with neutral Ensure (pH 7.0),
      acidified Ensure (pH 3.0), and apple juice (pH 3.0). Gastric emptying was
      assessed by (13)C sodium acetate breath test. RESULTS: From pH 7 to pH 3, the in
      vitro urease activity of intact bacteria increased sixfold. In contrast, urease
      activity of bacterial homogenates was inactivated by low pH. In vivo, urease
      activity, as measured by the UBT 20 minutes after meal ingestion, was higher with
      apple juice (delta (13)CO(2)=21.1; p=0.03) and acidified Ensure (delta
      (13)CO(2)=25.5; p=0.01) than with neutral Ensure (delta (13)CO(2)=12.5). Gastric
      emptying was faster with apple juice (T(max)=36.7 (8) minutes) but not with
      acidified Ensure (T(max)=63.3 (5) minutes; p=0.06) than with neutral Ensure
      (T(max)=65.0 (3) minutes; p=0.04). CONCLUSIONS: The higher UBT found with
      acidified compared with neutral test meals was independent of the emptying rates
      of the test meals but may have been due to medium acidity dependent activation of
      intra-bacterial urease in intact H pylori.

PMID- 12801948
TI  - Mortality study of 18 000 patients treated with omeprazole.
AB  - BACKGROUND: The long term safety of potent gastric acid suppressive therapy has
      yet to be established. METHOD: General practice record review at a median
      interval of 26 months followed by retrieval of details of all deaths within four
      years using the UK National Health Service Central Registers in 17 936 patients
      prescribed omeprazole in 1993-1995. Death rates were compared with general
      population rates. RESULTS: Records of 17 489 patients (97.5%) were examined. A
      total of 12 703 patients received further scripts for antisecretory drugs, 8097
      for omeprazole only (65.6%): 3097 patients have died. All cause mortality was
      higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals
      (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth
      year. There were significant mortality increases in the first year, falling to or
      below population expectation by the fourth year, for deaths ascribed to neoplasms
      (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13
      1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001).
      Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43);
      p<0.0001) persisted, although reduced. Increased mortality rates for cancers of
      the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI
      0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19);
      p<0.01) seen in the first year had disappeared by the fourth year but that for
      cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year
      1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of
      oesophageal cancer had the disease present at registration. Twenty seven of those
      remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or
      oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred
      in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and
      five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No
      relationships were detected with numbers of omeprazole scripts received.
      CONCLUSIONS: Increases in mortality associated with treatment are due to pre-
      existing illness, including pre-existing severe oesophageal disease. There was no
      evidence of an increased risk of oesophageal adenocarcinoma in those without
      oesophageal mucosal damage recorded at registration.

PMID- 12801949
TI  - Antagonism of ghrelin receptor reduces food intake and body weight gain in mice.
AB  - BACKGROUND AND AIMS: Ghrelin, an endogenous ligand for growth hormone
      secretagogue receptor (GHS-R), is an appetite stimulatory signal from the stomach
      with structural resemblance to motilin. We examined the effects of the gastric
      peptide ghrelin and GHS-R antagonists on energy balance and glycaemic control in
      mice. MATERIALS AND METHODS: Body weight, fat mass, glucose, insulin, and gene
      expression of leptin, adiponectin, and resistin in white adipose tissue (WAT)
      were measured after repeated administrations of ghrelin under a high fat diet.
      Gastric ghrelin gene expression was assessed by northern blot analysis. Energy
      intake and gastric emptying were measured after administration of GHS-R
      antagonists. Repeated administration of GHS-R antagonist was continued for six
      days in ob/ob obese mice. RESULTS: Ghrelin induced remarkable adiposity and
      worsened glycaemic control under a high fat diet. Pair feeding inhibited this
      effect. Ghrelin elevated leptin mRNA expression and reduced resistin mRNA
      expression. Gastric ghrelin mRNA expression during fasting was increased by a
      high fat diet. GHS-R antagonists decreased energy intake in lean mice, in mice
      with diet induced obesity, and in ob/ob obese mice; it also reduced the rate of
      gastric emptying. Repeated administration of GHS-R antagonist decreased body
      weight gain and improved glycaemic control in ob/ob obese mice. CONCLUSIONS:
      Ghrelin appears to be closely related to excess weight gain, adiposity, and
      insulin resistance, particularly under a high fat diet and in the dynamic stage.
      Gastric peptide ghrelin and GHS-R may be promising therapeutic targets not only
      for anorexia-cachexia but also for obesity and type 2 diabetes, which are
      becoming increasingly prevalent worldwide.

PMID- 12801950
TI  - Duodenal expression of iron transport molecules in untreated haemochromatosis
      subjects.
AB  - BACKGROUND AND AIMS: In HFE associated hereditary haemochromatosis, the duodenal
      enterocyte behaves as if iron deficient and previous reports have shown increased
      duodenal expression of divalent metal transporter 1 (DMT1) and iron regulated
      gene 1 (Ireg1) in affected subjects. In those studies, many patients had
      undergone venesection, which is a potent stimulus of iron absorption. Our study
      investigated duodenal expression of DMT1 (IRE and non-IRE), Ireg1, hephaestin,
      and duodenal cytochrome-b (Dyctb) in untreated C282Y homozygous haemochromatosis
      patients, iron deficient patients, and iron replete subjects. METHODS: Total RNA
      was extracted from duodenal biopsies and expression of the iron transport genes
      was assessed by ribonuclease protection assay. RESULTS: Expression of DMT1 (IRE)
      and Ireg1 was increased 3-5-fold in iron deficient subjects compared with iron
      replete subjects. Duodenal expression of DMT1 (IRE) and Ireg1 was similar in
      haemochromatosis patients and iron replete subjects but in haemochromatosis
      patients with elevated serum ferritin concentrations, both DMT1 (IRE) and Ireg1
      expression were inappropriately increased relative to serum ferritin
      concentration. Hephaestin and Dcytb levels were not upregulated in
      haemochromatosis. DMT1 (IRE) and Ireg1 levels showed significant inverse
      correlations with serum ferritin concentration in each group of patients.
      CONCLUSIONS: These findings are consistent with DMT1 (IRE) and Ireg1 playing
      primary roles in the adaptive response to iron deficiency. Untreated
      haemochromatosis patients showed inappropriate increases in DMT1 (IRE) and Ireg1
      expression for a given level of serum ferritin concentration, although the actual
      level of expression of these iron transport genes was not significantly different
      from that of normal subjects.

PMID- 12801951
TI  - Seroprevalence, correlates, and characteristics of undetected coeliac disease in
      England.
AB  - OBJECTIVE: To examine the seroprevalence, correlates, and characteristics of
      undetected coeliac disease in a large adult population sample in Cambridge, UK.
      METHODS: The Cambridge General Practice Health Study invited individuals from 12
      general practices, aged 45-76 years, to attend for a health survey that included
      a bone density measurement, between 1990 and 1995. A total of 7550 participants'
      serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of
      undetected coeliac disease was based on EMA positivity. Differences between EMA
      positive and negative participants of various physiological correlates and
      reported characteristics were estimated by multivariate logistic and linear
      regression and adjusted for age, sex, social class, and smoking behaviour.
      RESULTS: The seroprevalence of undetected coeliac disease in this general
      population sample aged 45-76 was 1.2% (95% confidence interval (CI) 0.9-1.4). EMA
      positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08),
      were more likely to have reported their general health as being "good or
      excellent" (odds ratio (OR) 1.76 (95% CI 0.90-3.46)), and were less likely to
      report being a current smoker (OR for current versus never 0.36 (95% CI 0.14
      0.90)) than EMA negative participants. EMA positivity was associated with an 8%
      reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean
      haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected
      serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis
      in EMA positive participants (OR 3.1 (95% CI 1.3-7.2)) and of mild anaemia (OR
      4.6 (95% CI 2.5-8.2)) compared with EMA negative participants. CONCLUSIONS:
      Undetected coeliac disease is likely to affect approximately 1% of the population
      of England aged 45-76 years, a value similar to several other countries. Those
      affected report "better health" but they do have an increased risk of
      osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular
      risk profile that may afford protection from ischaemic heart disease and stroke.

PMID- 12801952
TI  - Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal
      degeneration: pathological findings and management.
AB  - Delayed gastric emptying can be due to muscular, neural, or humoral
      abnormalities. In the absence of an identified cause, gastroparesis is labelled
      as idiopathic. We present the case of a patient with severe idiopathic
      gastroparesis. Pharmacological approaches failed, as well as reduction in gastric
      emptying resistance with pyloric injection of botulinum toxin and pyloroplasty.
      Therefore, subtotal gastrectomy was performed. Histological and
      immunohistochemical study of the resected specimen showed hypoganglionosis,
      neuronal dysplasia, and a marked reduction in both myenteric and intramuscular
      interstitial cells of Cajal. To our knowledge, this is the first time these rare
      histological findings have been described in a patient with idiopathic
      gastroparesis.

PMID- 12801953
TI  - Influence of body posture on intestinal transit of gas.
AB  - BACKGROUND: Patients describe that body posture may affect their abdominal
      bloating, distension, and flatulence, but whether changes in position have
      objectively demonstrable effects, either beneficial or deleterious, has not been
      investigated. AIM: To determine the effect of body posture, upright versus
      supine, on intestinal transit of gas loads. SUBJECTS: Eight healthy subjects
      without gastrointestinal symptoms. METHODS: In each subject a gas mixture was
      continuously infused into the jejunum (12 ml/min) for three hours, and gas
      evacuation, clearance of a non- absorbable gaseous marker, perception, and
      abdominal girth were measured. Paired studies were randomly performed in each
      subject on separate days in the upright and supine positions. RESULTS: In the
      upright position, intestinal gas retention was much smaller than when supine (13
      (52) ml v 146 (75) ml retention at 60 minutes, respectively; p<0.05), and
      clearance of the gas marker was expedited (72 (10)% clearance v 49 (16)% at 60
      minutes, respectively; p<0.05). The gas challenge test was well tolerated both in
      the upright and supine positions without abdominal distension. CONCLUSION: Body
      posture has a significant influence on intestinal gas propulsion: transit is
      faster in the upright position than when supine.

PMID- 12801954
TI  - Double blind, placebo controlled trial of two probiotic strains in interleukin 10
      knockout mice and mechanistic link with cytokine balance.
AB  - BACKGROUND: Prophylactic efficacy against colitis following lactobacillus
      consumption in interleukin 10 (IL-10) knockout (KO) mice has been reported.
      Whether this applies equally to other probiotic strains is unknown, and the
      mechanism is unclear. AIMS: (1) To compare the effect of feeding Lactobacillus
      salivarius subspecies salivarius 433118 and Bifidobacterium infantis 35624
      against placebo on enterocolitis, the intestinal microflora, and (2) to compare
      the systemic immunological response to in vitro microbial challenge in probiotic
      fed and control IL-10 KO mice. METHODS: Three groups of 10 IL-10 KO mice were fed
      fermented milk products containing Lb salivarius 433118 at 10(9) CFU/ml, B
      infantis 35624 at 10(8) CFU/ml, and unmodified milk, respectively, for 19 weeks.
      Faecal samples were taken at regular intervals to confirm gut transit, recovery
      of fed probiotics, and to assess the impact on the microflora. At sacrifice, the
      bowels were histologically scored. Cytokine production from Peyers' patches and
      splenocytes was measured in vitro by ELISA. RESULTS: Faecal recovery of
      probiotics was confirmed in all probiotic fed mice but not in controls. Colonic
      and caecal inflammatory scores were significantly decreased in both groups of
      probiotic fed mice (p<0.05). Proinflammatory cytokine production by Peyers'
      patches and splenocytes was significantly reduced in probiotic fed animals
      whereas transforming growth factor beta (TGF-beta) levels were maintained.
      CONCLUSION: Both Lactobacillus salivarius 433118 and Bifidobacterium infantis
      35624 significantly attenuate colitis in this murine model. Attenuation of
      colitis is associated with a reduced ability to produce Th1-type cytokines
      systemically and mucosally, while levels of TGF-beta are maintained.

PMID- 12801955
TI  - Local delivery of adenoviral vectors encoding murine interleukin 10 induces
      colonic interleukin 10 production and is therapeutic for murine colitis.
AB  - INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1
      T cell mediated colitis with many similarities to Crohn's disease. Daily
      injections of IL-10 are unable to induce remission in mice with established
      disease. In contrast, we have shown previously that intravenous administration of
      adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and
      leads to long term disease suppression with profound systemic immunoregulatory
      changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces
      localised colonic IL-10 expression without systemic immune suppression, and
      assess its therapeutic efficacy in IL-10-/- mice with established colitis.
      RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL- 10-/
      mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates
      harvested one week later. IL-10-/- mice with established colitis treated with an
      enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission
      whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS)
      treated mice developed progressive disease. After four weeks, the histological
      score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of
      Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In
      addition, the stool concentration of IL-1beta over the four week experiment was
      significantly higher in mice treated with saline or Adv0 than in those treated
      with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis
      in IL-10-/- mice without the systemic effects seen after intravenous
      administration. Gene therapy strategies using adenoviral vectors encoding
      immunoregulatory cytokines may prove to be a potent approach to the treatment of
      chronic inflammatory diseases such as Crohn's disease.

PMID- 12801956
TI  - Live probiotics protect intestinal epithelial cells from the effects of infection
      with enteroinvasive Escherichia coli (EIEC).
AB  - BACKGROUND: The colonic epithelium maintains a life long reciprocally beneficial
      interaction with the colonic microbiota. Disruption is associated with mucosal
      injury. AIMS: We hypothesised that probiotics may limit epithelial damage induced
      by enteroinvasive pathogens, and promote restitution. METHODS: Human intestinal
      epithelial cell lines (HT29/cl.19A and Caco-2) were exposed to enteroinvasive
      Escherichia coli (EIEC 029:NM), and/or probiotics (Streptococcus thermophilus
      (ST), ATCC19258, and Lactobacillus acidophilus (LA), ATCC4356). Infected cells
      and controls were assessed for transepithelial resistance, chloride secretory
      responses, alterations in cytoskeletal and tight junctional proteins, and
      responses to epidermal growth factor (EGF) stimulation. RESULTS: Exposure of cell
      monolayers to live ST/LA, but not to heat inactivated ST/LA, significantly
      limited adhesion, invasion, and physiological dysfunction induced by EIEC.
      Antibiotic killed ST/LA reduced adhesion somewhat but were less effective in
      limiting the consequences of EIEC invasion of cell monolayers. Furthermore, live
      ST/LA alone increased transepithelial resistance, contrasting markedly with the
      fall in resistance evoked by EIEC infection, which could also be blocked by live
      ST/LA. The effect of ST/LA on resistance was accompanied by maintenance (actin,
      ZO-1) or enhancement (actinin, occludin) of cytoskeletal and tight junctional
      protein phosphorylation. ST/LA had no effect on chloride secretion by themselves
      but reversed the increase in basal secretion evoked by EIEC. EIEC also reduced
      the ability of EGF to activate its receptor, which was reversed by ST/LA.
      CONCLUSIONS: Live ST/LA interact with intestinal epithelial cells to protect them
      from the deleterious effect of EIEC via mechanisms that include, but are not
      limited to, interference with pathogen adhesion and invasion. Probiotics likely
      also enhance the barrier function of naive epithelial cells not exposed to any
      pathogen.

PMID- 12801957
TI  - Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a
      randomised controlled trial.
AB  - BACKGROUND: Tumour necrosis factor production is increased in the mucosa of
      patients with active ulcerative colitis. The benefits of infliximab in Crohn's
      disease are established. We investigated its efficacy in ulcerative colitis.
      METHODS: We conducted a randomised placebo controlled trial of infliximab (5
      mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions
      were given at weeks 0 and 2. Disease activity and quality of life were recorded
      over eight weeks of follow up. Remission was defined as an ulcerative colitis
      symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not
      in remission were offered open label infliximab 10 mg/kg and reviewed two weeks
      later. RESULTS: After two weeks, there was no statistically significant
      difference between the infliximab and placebo groups in the proportion of
      patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval
      (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were
      39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement
      in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82,
      Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v
      30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was
      not significantly different between the groups (p=0.22 and 0.3, respectively,
      Mann-Whitney U test). Twenty eligible patients were given open labelled
      infusions. Remission was achieved in 3/11 (27%) patients initially treated with
      infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data
      do not support the use of infliximab in the management of moderately active
      glucocorticoid resistant ulcerative colitis.

PMID- 12801958
TI  - Fluorescence endoscopy for the detection of low and high grade dysplasia in
      ulcerative colitis using systemic or local 5-aminolaevulinic acid sensitisation.
AB  - BACKGROUND AND AIMS: Longstanding ulcerative colitis (UC), especially in the
      presence of epithelial dysplasia, is associated with an increased risk of
      developing cancer. As dysplasia is not visible during routine endoscopy, at least
      40-50 random biopsies in four quadrants every 10 cm are recommended. Fluorescence
      endoscopy after sensitisation with 5-aminolaevulinic acid (5-ALA) was assessed
      for the detection of dysplasia in ulcerative colitis by taking optical guided
      biopsies. 5-ALA is converted intracellularly into the sensitiser protoporphyrin
      IX which accumulates selectively in neoplastic tissue allowing the detection of
      dysplasia by typical red fluorescence after illumination with blue light.
      METHODS: In 37 patients with UC, 54 examinations were performed with fluorescence
      endoscopy after oral (20 mg/kg) or local (either with an enema or by spraying the
      mucosa with a catheter) sensitisation with 5-ALA. A total of 481 biopsies of red
      fluorescent (n=218) and non-fluorescent (n=263) areas of the colonic mucosa were
      taken. RESULTS: Forty two biopsies in 12 patients revealed either low grade
      (n=40) or high grade (n=2) dysplasia. Sensitivity of fluorescence for dysplastic
      lesions was excellent and ranged from 87% (95% confidence interval (CI) 0.73
      1.00) to 100% (95% CI 1.00-1.00) after local sensitisation, in contrast with only
      43% (95% CI 0.17-0.69) after systemic administration. Specificity did not differ
      for both forms of local sensitisation (enema 51% (95% CI 0.44-0.57) and spray
      catheter 62% (95% CI 0.51-0.73)); after systemic sensitisation specificity was
      73% (95% CI 0.69-0.83). Negative predictive values of non-fluorescent mucosa for
      exclusion of dysplasia were very high; 89% after systemic sensitisation and 98
      100% after local sensitisation. Positive predictive values were 13% and 14% after
      local sensitisation with enema and spray catheter, and 21% after oral
      sensitisation with 20 mg/kg ALA. The overall number of biopsies per examination
      was less than five from fluorescent positive areas. CONCLUSION: Fluorescence
      endoscopy after 5-ALA sensitisation is a possible tool to visualise dysplastic
      lesions in ulcerative colitis using 5-ALA sensitisation. Local sensitisation is a
      promising alternative approach compared with systemic administration of 5-ALA. A
      randomised controlled study is now indicated to compare the efficacy of
      endoscopic fluorescence detection with the standard technique of four quadrant
      random biopsies.

PMID- 12801959
TI  - Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of
      the human pancreas.
AB  - BACKGROUND: The exocrine pancreas secretes large volumes of isotonic fluid, most
      of which originates from the ductal system. The role of aquaporin (AQP) water
      channels in this process is unknown. METHODS: Expression and localisation of
      known AQP isoforms was examined in normal human pancreas, pancreatic
      adenocarcinoma, and pancreatic cell lines of ductal origin (Capan-1, Capan-2, and
      HPAF) using reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. RESULTS: Messenger RNAs for AQP1, -3, -4, -5, and -8 were
      detected in normal pancreas and in pancreatic adenocarcinoma. The cell lines
      expressed AQP3, -4, and -5 but lacked AQP1 and AQP8. Immunohistochemistry of
      normal pancreas revealed that AQP1 is strongly expressed in centroacinar cells
      and in both the apical and basolateral domains of intercalated and intralobular
      duct epithelia. AQP1 expression declined with distance along the small
      interlobular ducts and was not detectable in larger interlobular ducts. AQP3 and
      AQP4 were not detectable by immunohistochemistry. AQP5 was observed at the apical
      membrane of intercalated duct cells and also in duct associated mucoid glands.
      AQP8 was confined to the apical pole of acinar cells. Both AQP1 and AQP5 were
      colocalised with cystic fibrosis transmembrane conductance regulator (CFTR) at
      the apical membrane of intercalated duct cells. CONCLUSIONS: AQP1 and AQP5 are
      strongly expressed in the intercalated ducts of the human pancreas. Their
      distribution correlates closely with that of CFTR, a marker of ductal electrolyte
      secretion. This suggests that fluid secretion is concentrated in the terminal
      branches of the ductal tree and that both AQP1 and AQP5 may play a significant
      role.

PMID- 12801960
TI  - Expression and regulation of scavenger receptor class B type I (SR-BI) in gall
      bladder epithelium.
AB  - BACKGROUND AND AIMS: Biliary lipid absorption by the gall bladder mucosa and the
      cholesterol content of the gall bladder wall appear to play a role in cholesterol
      gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates
      cellular cholesterol uptake, we studied its expression in human and murine gall
      bladders, its regulation by increased biliary lipid content, and its role in gall
      stone formation. METHODS AND RESULTS: Using immunohistochemistry, SR-BI was found
      in the apical domain of human gall bladder epithelial cells. Immunoblotting of
      isolated membranes from gall bladder epithelial cells showed a specific signal
      for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall
      bladder epithelium. Using western blot analysis, an inverse relationship was
      observed between biliary cholesterol concentration and SR-BI expression in murine
      gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI
      deficient mice, gall bladder wall cholesterol content and gall stone formation
      were not found to be dependent on SR-BI expression. CONCLUSIONS: (i) SR-BI is
      expressed in both human and murine gall bladder epithelium; (ii) biliary
      cholesterol hypersecretion is associated with decreased gall bladder SR-BI
      expression in mice; and (iii) murine SR-BI is not essential in controlling gall
      bladder wall cholesterol content and gall stone formation during diet induced
      cholelithiasis.

PMID- 12801961
TI  - Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the genetic
      aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known
      cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease.
      PATIENTS AND METHODS: Sixty nine Finnish ICP patients were prospectively
      interviewed for a family history of ICP, and clinical features were compared in
      patients with familial ICP (patients with a positive family history, n=11) and
      sporadic patients (patients with no known family history of ICP, n=58). For
      molecular genetic analysis, 16 individuals from two independently ascertained
      Finnish ICP families were genotyped for the flanking markers for BSEP, FIC1, and
      MDR3. RESULTS: The pedigree structures in 16% (11/69) of patients suggested
      dominant inheritance. Patients with familial ICP had higher serum
      aminotransferase levels and a higher recurrence risk (92% v 40%). Both
      segregation of haplotypes and multipoint linkage analysis excluded BSEP, FIC1,
      and MDR3 genes in the studied pedigrees. Additionally, the MDR3 gene, previously
      shown to harbour mutations in ICP patients, was negative for mutations when
      sequenced in four affected individuals from the two families. CONCLUSIONS: These
      results support the hypothesis that the aetiology of ICP is heterogeneous and
      that ICP is due to a genetic predisposition in a proportion of patients. The
      results of molecular genetic analysis further suggest that the previously
      identified three cholestasis genes are not likely to be implicated in these
      Finnish ICP families with dominant inheritance.

PMID- 12801962
TI  - Ten year incidence of HCV infection in northern Italy and frequency of
      spontaneous viral clearance.
AB  - BACKGROUND: Little is known of the incidence of hepatitis C virus (HCV)
      infection, and the frequency of spontaneous viral clearance in the general
      population is unknown. We conducted an epidemiological study in two Apennine
      towns in northern Italy. METHODS: Anti-HCV (ELISA and RIBA third generation) and
      HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult
      general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context
      of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV
      positive subjects and sex and age matched controls were recalled in order to
      identify risk factors for acquiring HCV infection and to assess the family
      composition of anti-HCV+ subjects. RESULTS: For 1646 subjects, sera were
      available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57
      (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were
      recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty
      three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for
      44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of
      alanine aminotransferase with respect to controls (p<0.005), as did subjects
      infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven
      of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV
      RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to
      families containing more than one infected member. Married couples accounted for
      10 of these 16 subjects. In four of these five married couples, HCV genotype was
      identical in the two spouses. CONCLUSIONS: In rural northern Italy, the adult
      incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings
      suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab.
      Interfamilial transmission seems to have a role in the spread of infection.

PMID- 12801963
TI  - Impact of human immunodeficiency virus (HIV) infection on the progression of
      liver fibrosis in hepatitis C virus infected patients.
AB  - OBJECTIVES: To compare the rate of hepatic fibrosis progression in hepatitis C
      virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected
      patients, and to identify factors that may influence fibrosis progression.
      PATIENTS AND METHODS: A total of 153 HCV infected and 55 HCV-HIV coinfected
      patients were identified from two London hospitals. Eligible patients had known
      dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver
      biopsy, which was graded using the Ishak score. Univariate and multivariate
      logistic regression analyses were used to identify factors associated with
      fibrosis progression rate and the development of advanced fibrosis (stages 3 and
      4). RESULTS: The estimated median fibrosis progression rate was 0.17 units/year
      (interquartile range (IQR) 0.10-0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07
      0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from
      HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at
      infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase
      (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy
      were all independently associated with more rapid fibrosis progression. ALT was
      correlated with histological index (r=0.35, p<0.001). A CD4 cell count < or =250
      x 10(6)/l was independently associated with advanced liver fibrosis (odds ratio
      5.36 (95% confidence interval 1.26-22.79)) and was also correlated with a higher
      histological index (r=-0.42, p=0.002). CONCLUSION: HIV infection modifies the
      natural history of HCV by accelerating the rate of fibrosis progression by 1.4
      fold, and the development of advanced fibrosis threefold. A low CD4 cell count
      was independently associated with advanced disease and correlated with higher
      histological index, which suggests that early antiretroviral therapy may be of
      benefit in slowing HCV progression in coinfected patients.

PMID- 12801964
TI  - Enhanced renal ammonia excretion following volume expansion in patients with well
      compensated cirrhosis of the liver.
AB  - BACKGROUND AND AIMS: In patients with cirrhosis, hepatic encephalopathy is often
      precipitated by dehydration. This study tests the hypothesis that volume
      expansion in cirrhotic patients increases renal ammonia excretion. PATIENTS AND
      METHODS: Sixteen well compensated cirrhotic patients (mean Pugh score 6.7 (SEM
      0.4)) were studied after an overnight fast. One litre of 0.9% saline was
      administered to patients intravenously over one hour. Plasma and urinary ammonia
      and sodium, renal plasma flow (RPF), glomerular filtration rate (GFR), plasma
      renin activity (PRA), and angiotensin II (ANG II) were measured before, during,
      and two hours after saline infusion. RESULTS: Saline infusion resulted in a
      significant reduction in plasma ammonia (93 (SEM 7) to 56 (4) micromol/l; p<0.05)
      and RPF and GFR increased (p<0.05). Urinary ammonia excretion increased (p<0.05)
      significantly. There was a significant reduction in ANG II and PRA (p<0.05 for
      each) and the change in ammonia excretion correlated directly with the change in
      urinary sodium excretion (p<0.007), ANG II (p<0.002), and PRA (p<0.01). The mean
      increase in urinary ammonia excretion during the observation period was 1.08
      mmol. Assuming a volume of distribution of 45 litres, the corresponding change in
      whole body ammonia during the same period was 1.67 mmol. CONCLUSION: The results
      of this study suggest that volume expansion reduces plasma ammonia concentration
      by increasing ammonia excretion and reducing ammoniagenesis.

PMID- 12801965
TI  - Hepatic 31P MRS in rat models of chronic liver disease: assessing the extent and
      progression of disease.
AB  - BACKGROUND: Hepatic adenosine triphosphate (ATP) levels are an accurate
      reflection of functioning hepatic mass following surgical resections and acute
      liver injury. OBJECTIVE: To determine whether hepatic ATP levels can serve as a
      non-invasive means of documenting progression of chronic liver disease to
      cirrhosis. METHODS: In vivo phosphorus-31 magnetic resonance spectroscopy ((31)P
      MRS) was performed in three animal models of chronic liver disease. Sixty six
      adult Sprague- Dawley rats were subjected to either thioacetamide, carbon
      tetrachloride (CCl(4)), or common bile duct ligation (CBDL) to induce liver
      disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples,
      and liver biopsies (when appropriate) were obtained throughout and/or on
      completion of the study. RESULTS: Over the course of the chronic liver disease, a
      progressive decrease in hepatic ATP levels was consistently observed in each
      model. The findings were most striking when end stage liver disease (cirrhosis)
      was established. The reduction in hepatic ATP levels correlated with significant
      changes in serum albumin concentrations (CCl(4) and CBDL models) and the extent
      of hepatocyte loss seen histologically (all models). CONCLUSION: The results of
      this study indicate that during progression of chronic liver disease to
      cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition,
      changes in hepatic ATP levels correlate with changes in liver function and
      histology. Thus hepatic (31)P MRS provides a non-invasive means of documenting
      the severity and progression of parenchymal and cholestatic models of chronic
      liver disease in rats.

PMID- 12801966
TI  - Increased tumour necrosis factor alpha production in mesenteric lymph nodes of
      cirrhotic patients with ascites.
AB  - BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with
      bacterial translocation may participate in circulatory alterations of cirrhosis.
      AIM: To investigate whether cirrhotic patients present an increased local
      generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph
      nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis
      factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive
      reverse transcription-polymerase chain reaction, and by enzyme immunoassay and
      immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not
      different between cirrhotics and controls. Protein and mRNA TNF levels in
      mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05).
      Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics.
      Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than
      patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF
      levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh
      score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin
      and blood TNF levels. The strongest association, confirmed by multivariate
      analysis, was with the presence of ascites (p<0.001). Bacterial infections after
      transplantation, mainly by enteric bacteria, were only detected in patients with
      high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION:
      Patients with advanced liver cirrhosis, and especially with ascites, have
      increased local production of TNF in mesenteric lymph nodes that, in common with
      experimental cirrhosis, may also be induced by bacterial translocation.

PMID- 12801969
TI  - Caution with the use of cyclosporin in pregnancy.

PMID- 12801967
TI  - ATP binding cassette transporter gene expression in rat liver progenitor cells.
AB  - BACKGROUND AND AIM: Liver regeneration after severe liver damage depends in part
      on proliferation and differentiation of hepatic progenitor cells (HPCs). Under
      these conditions they must be able to withstand the toxic milieu of the damaged
      liver. ATP binding cassette (ABC) transporters are cytoprotective efflux pumps
      that may contribute to the preservation of these cells. The aim of this study was
      to determine the ABC transporter phenotype of HPCs. METHODS: HPC activation was
      studied in rats treated with 2- acetylaminofluorene (2-AAF) followed by partial
      hepatectomy (PHx). ABC transporter gene expression was determined by real time
      detection reverse transcription-polymerase chain reaction in isolated HPCs,
      hepatocytes, cholangiocytes, and cultured progenitor cell-like RLF phi 13 cells
      and by immunohistochemistry of total liver samples. ABC transporter efflux
      activity was studied in RLF phi 13 cells by flow cytometry. RESULTS: 2-AAF/PHx
      treated animals showed increased hepatic mRNA levels of the genes encoding
      multidrug resistance proteins Mdr1b, Mrp1, and Mrp3. Immunohistochemistry
      demonstrated expression of Mrp1 and Mrp3 proteins in periportal progenitor cells
      and of the Mdr1b protein in periportal hepatocytes. Freshly isolated Thy-1
      positive cells and cultured RLF phi 13 progenitor cells highly expressed Mrp1 and
      Mrp3 mRNA while the hepatocyte specific transporters Mdr2, Bsep, Mrp2, and Mrp6
      were only minimally expressed. Blocking Mrp activity by MK-571 resulted in
      accumulation of the Mrp specific substrate carboxyfluorescein in RLF phi 13
      cells. CONCLUSION: HPCs express high levels of active Mrp1 and Mrp3. These may
      have a cytoprotective role in conditions of severe hepatotoxicity.

PMID- 12801970
TI  - Coeliac disease: is case finding the correct ethical and logistical approach?

PMID- 12801971
TI  - Severe polyneuropathy complicating active Crohn's disease: rapid response to
      Infliximab.

PMID- 12801972
TI  - Guidelines for colonoscopic screening in acromegaly are inconsistent with those
      for other high risk groups.

PMID- 12801973
TI  - Multiple focal nodular hyperplasia of the liver in a patient with prostatic
      cancer.

PMID- 12801974
TI  - Transient ischaemic colitis following an aeroplane flight.

PMID- 12801975
TI  - New imaging techniques: promise or passe.

PMID- 12801976
TI  - Epigenetic characteristics of bovine donor cells for nuclear transfer: levels of
      histone acetylation.
AB  - Donor cell type, cell-cycle stage, and passage number of cultured cells all
      affect the developmental potential of cloned embryos. Because acetylation of the
      histones on nuclear chromatin is an important aspect of gene activation, the
      present study investigated the differences in histone acetylation of bovine
      fibroblast and cumulus cells at various passages and cell-cycle stages. The
      acetylation was qualitatively analyzed by epifluorescent confocal microscopy and
      quantitatively by immunofluorescent flow cytometry. Specifically, we studied
      levels of histone H4 acetylated at lysine 8 and histone H3 acetylated at lysine
      18; acetylation at these lysine residues is among the most common for these
      histone molecules. We also studied levels of linker histone H1 in donor cells.
      Our results show that stage of cell cycle, cell type, and number of cell passages
      all had an effect on histone content. Histone H1 and acetyl histone H3 increased
      with cell passage (passages 5-15) in G0/G1- and G2/M-stage cumulus and fibroblast
      cells. We also found that acetyl histone H4 was lower in early versus late cell
      passages (passage 5 vs. 15) for G0/G1-stage cumulus cells. In both cell types
      examined, acetyl histones increased with cell-cycle progression from G0/G1 into
      the S and G2/M phases. These results indicate that histone acetylation status is
      remodeled by in vitro cell culture, and this may have implications for nuclear
      transfer.

PMID- 12801977
TI  - Characterization of histone H2A.X expression in testis and specific labeling of
      germ cells at the commitment stage of meiosis with histone H2A.X promoter
      enhanced green fluorescent protein transgene.
AB  - To study the complex molecular mechanisms of mammalian spermatogenesis, it would
      be useful to be able to isolate cells at each stage of differentiation,
      especially at the stage in which the cells switch from mitosis to meiosis.
      Currently, no useful marker proteins or gene promoters specific to this important
      stage are known. We report here a transgenic mouse line that under the control of
      the promoter for a histone variant, H2A.X, expressed an enhanced green
      fluorescent protein (EGFP) in cells at the stage of the mitosis-meiosis switch.
      Endogenous H2A.X is expressed in type A spermatogonia through meiotic prophase
      spermatocytes in testis and in some somatic cells. However, despite the fact that
      its expression was driven by the H2A.X promoter, the EGFP expressed in the
      transgenic mice specifically labeled only the intermediate spermatogonia stage
      through the meiotic prophase spermatocyte stage in transgenic mice containing the
      -600-base pair H2A.X promoter/EGFP construct. Type A spermatogonia and somatic
      cells of other organs were not labeled. This expression pattern made it possible
      to isolate living cells from the testis of the transgenic mice at the stage of
      the mitosis-meiosis switch in spermatogenesis using EGFP fluorescence.

PMID- 12801978
TI  - Fertility and germline transmission of donor haplotype following germ cell
      transplantation in immunocompetent goats.
AB  - Transplantation of spermatogonial stem cells into syngeneic or immunosuppressed
      recipient mice or rats can result in donor-derived spermatogenesis and fertility.
      Recently, this approach has been employed to introduce a transgene into the male
      germline. Germ-cell transplantation in species other than laboratory rodents, if
      successful, holds great promise as an alternative to the inefficient methods
      currently available to generate transgenic farm animals that can produce
      therapeutic proteins in their milk or provide organs for transplantation to
      humans. To explore whether germ-cell transplantation could result in donor
      derived spermatogenesis and fertility in immunocompetent recipient goats, testis
      cells were transplanted from transgenic donor goats carrying a human alpha-1
      antitrypsin expression construct to the testes of sexually immature wild-type
      recipient goats. After puberty, sperm carrying the donor-derived transgene were
      detected in the ejaculates of two out of five recipients. Mating of one recipient
      resulted in 15 offspring, one of which was transgenic for the donor-derived
      transgene. This is the first report of donor cell-derived sperm production and
      transmission of the donor haplotype to the next generation after germ-cell
      transplantation in a nonrodent species. Furthermore, these results indicate that
      successful germ-cell transplantation is feasible between immunocompetent,
      unrelated animals. In the future, transplantation of genetically modified germ
      cells may provide a more efficient alternative for production of transgenic
      domestic animals.

PMID- 12801979
TI  - Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and
      promotes primordial follicle development.
AB  - The growth and development of follicles within the ovary are highly dependent on
      autocrine and paracrine signaling involving growth factors from granulosa cells,
      theca cells, stromal interstitial cells, and the oocytes. The growth factor bone
      morphogenetic protein-4 (BMP-4) and its receptor (BMPR-IB) have been detected in
      ovaries, and a mutation in BMPR-IB has been associated with abnormal ovulation
      rate. The objective of the current study was to examine the role that BMP-4 plays
      in the early stages of primordial follicle development. Ovaries from 4-day-old
      rats were placed into a whole-ovary organ culture system for 2 wk to investigate
      the effect that treatment with exogenous BMP-4 has on early follicle development.
      BMP-4-treated ovaries had a significantly higher proportion of developing primary
      follicles and fewer arrested primordial follicles than did untreated controls.
      This indicates that BMP-4 promotes primordial follicle development and the
      primordial-to-primary follicle transition. Ovaries were also treated with
      neutralizing antibody against BMP-4 to determine effects of removing endogenously
      produced BMP-4. Interestingly, ovaries treated with BMP-4 antibody were markedly
      smaller than controls. This was associated with a progressive loss of oocytes and
      primordial follicles, a progressive increase in cellular apoptosis, and an
      accompanying loss of normal ovarian tissue morphology over time.
      Immunocytochemistry localized BMP-4 protein to isolated stromal cell populations,
      selected stromal cells (i.e., pretheca cells) associated with developing
      primordial follicles, and the basement membrane of follicles. Ovaries were
      treated with BMP-4 and RNA collected after organ culture to determine whether BMP
      4 signaling affects expression of other growth factors. Kit ligand and basic
      fibroblast growth factor expression was unchanged, but TGFalpha expression was
      decreased in whole ovaries. Taken together, these data suggest that BMP-4 plays
      an important role in promoting the survival and development of primordial
      follicles in the neonatal ovary.

PMID- 12801980
TI  - Variant of perivitelline membrane glycoprotein ZPC of Japanese quail (Coturnix
      japonica) lacking its cytoplasmic tail exhibits the retention in the endoplasmic
      reticulum of Chinese hamster ovary (CHO-K1) cells.
AB  - Avian perivitelline membrane, an investment homologous to the mammalian zona
      pellucida, is composed of at least two glycoproteins. Our previous studies
      demonstrated that one of its components, ZPC, which is synthesized in the ovarian
      granulosa cells, is secreted after carboxy-terminal proteolytic processing, and
      this event is a prerequisite event for ZPC secretion in quail. In the present
      study, we examined the role of the cytoplasmic tail, which is successfully
      removed after proteolytic processing, in membrane transport, proteolytic
      processing, and the secretion of quail ZPC. In pursuit of this, we produced a
      truncated ZPC mutant lacking the cytoplasmic tail located in its C-terminus and
      examined its expression in the mammalian cell line. Western blot analyses
      demonstrated that the cytoplasmic tail-deficient ZPC was neither secreted nor
      underwent proteolytic processing in the cells. Immunofluorescence analysis and
      the acquisition of resistance to endoglycosidase H digestion of the cytoplasmic
      tail-deficient ZPC demonstrated that the deletion of the cytoplasmic tail
      interferes with the intracellular trafficking of the protein from the endoplasmic
      reticulum to the Golgi apparatus. These results indicate that the cytoplasmic
      tail of quail ZPC might possess the determinant responsible for the efficient
      transport of the newly synthesized ZPC from the endoplasmic reticulum to the
      Golgi apparatus.

PMID- 12801981
TI  - Amino acid transport regulates blastocyst implantation.
AB  - Mouse blastocyst outgrowth in vitro and probably implantation in vivo require
      amino acid signaling via the target of rapamycin (TOR) pathway. This signaling
      does not simply support protein synthesis and trophoblast differentiation.
      Rather, it regulates development of trophoblast protrusive activity and may act
      as a developmental checkpoint for implantation. Moreover, intracellular amino
      acids per se are insufficient to elicit TOR signaling. Instead, de novo transport
      of amino acids, and particularly of leucine, stimulate mTOR activity at the
      blastocyst stage. The activity of the broad-scope and yet leucine-selective amino
      acid transport system B0,+ could produce such increases in intracellular amino
      acid concentrations. For example, system B0,+ uses a Na+ gradient to drive amino
      acid uptake, and the Na+ concentration in uterine secretions increases by nearly
      two-fold about 18 h before implantation. The resultant mTOR signaling could
      trigger polyamine, insulin-like growth factor II, and nitric oxide production in
      blastocysts and the increased cell motility sometimes associated with synthesis
      of these bioactive molecules.

PMID- 12801982
TI  - Determination of onset of apoptosis in granulosa cells of the preovulatory
      follicles in the bonnet monkey (Macaca radiata): correlation with mitogen
      activated protein kinase activities.
AB  - During reproductive life, only a selected few ovarian follicles mature and
      ovulate, while the vast majority of follicles undergo a degenerative process
      called atresia. Recent studies have indicated that follicular atresia is mediated
      through apoptosis of follicular granulosa cells. The objectives of the present
      study were to determine the time of onset of apoptosis in granulosa cells of
      preovulatory follicles and to evaluate the consequences of gonadotropin
      withdrawal on mitogen-activated protein (MAP) kinase activities. Bonnet monkeys
      (Macaca radiata) undergoing controlled ovarian stimulation cycles were utilized
      for stimulation of multiple follicles, and granulosa cells were retrieved from
      preovulatory follicles at 24, 48, 72, and 96 h after stopping gonadotropin
      treatment. Serum and follicular fluid estradiol concentrations were highest at 24
      h but declined precipitously (P < 0.05) to reach the lowest concentrations at 96
      h; however, progesterone concentrations during this period did not increase,
      indicating the absence of luteinization. Quantitative analysis of genomic DNA by
      3'-end labeling revealed the presence of low-molecular-weight fragments from 48 h
      onward, but by agarose gel electrophoresis, DNA laddering could be visualized
      only after 72 h. Messenger RNA expression for Bax, caspase-2, and caspase-3
      increased with the onset of apoptosis. Immunoblot analysis of MAP kinases in
      lysates of granulosa cells (48-72 h) indicated increased (P < 0.05) levels of
      phosphorylated extracellular response kinase-1 and -2, Jun N-terminal kinase
      (JNK)-1 and -2, and p38. However, in vitro kinase assay data indicated that only
      phospho-JNK and -p38 activities were higher at 72 h compared to 24 h. These
      results demonstrate that granulosa cells of preovulatory follicles undergo
      apoptosis and that increased activities of phospho-JNK and -p38 are correlated
      with apoptosis in the primate.

PMID- 12801983
TI  - Trehalose-enhanced fluidity of the goat sperm membrane and its protection during
      freezing.
AB  - In an attempt to find a suitable freezing method for goat semen, two experiments
      were conducted to study the influence of trehalose on the cryopreservation of
      goat spermatozoa. In experiment 1, goat spermatozoa were frozen in trehalose
      extender (0.375 M) alone (100%) or at different combinations of trehalose with
      Tris-citric acid-glucose (TCG) extender (0%, 25%, 50%, 75%). Final concentrations
      of 20% (v:v) egg yolk and 4% (v:v) glycerol were employed in the extenders
      (osmolality = 370, pH = 7). Sperm motility was assessed using a computer-assisted
      sperm analysis system and acrosome integrity was assessed using fluorescein
      isothiocyanate-labeled peanut agglutinin (FITC-PNA). The sperm-motility
      parameters improved significantly by increasing the concentration of trehalose (P
      < 0.05) and significantly high recovery rates for the motility parameters were
      also achieved by a high concentration of trehalose (P < 0.05). Motility of the
      frozen-thawed spermatozoa after a 3-h incubation improved significantly with
      increasing concentrations of trehalose in the extender (P < 0.05). The 75% and
      100% trehalose extenders yielded a significant increase in the percentage of
      spermatozoa with intact acrosome (P < 0.05). In experiment 2, merocyanine 540/Yo
      Pro staining was used to study the influence of trehalose on membrane fluidity
      compared with that of sucrose and TCG. Percentage of cells with high merocyanine
      fluorescence was significantly higher in spermatozoa treated with trehalose than
      sucrose or TCG (P < 0.05), indicating a significantly highest membrane fluidity
      of sperm samples extended with trehalose solution. We thus conclude that the
      substitution of a Tris-citric acid diluent composition with trehalose
      significantly improves the freezability of goat spermatozoa. Furthermore, the
      cryoprotective effects of trehalose observed in this study may be due to enhanced
      sperm membrane fluidity before freezing.

PMID- 12801984
TI  - Effects of donor cell type and genotype on the efficiency of mouse somatic cell
      cloning.
AB  - Although it is widely assumed that the cell type and genotype of the donor cell
      affect the efficiency of somatic cell cloning, little systematic analysis has
      been done to verify this assumption. The present study was undertaken to examine
      whether donor cell type, donor genotype, or a combination thereof increased the
      efficiency of mouse cloning. Initially we assessed the developmental ability of
      embryos that were cloned from cumulus or immature Sertoli cells with six
      different genotypes (i.e., 2 x 6 factorial). Significantly better cleavage rates
      were obtained with cumulus cells than with Sertoli cells (P < 0.005, two-way
      ANOVA), which probably was due to the superior cell-cycle synchrony of cumulus
      cells at G0/G1. After embryo transfer, there was a significant effect of cell
      type on the birth rate, with Sertoli cells giving the better result (P < 0.005).
      Furthermore, there was a significant interaction (P < 0.05) between the cell type
      and genotype, which indicates that cloning efficiency is determined by a
      combination of these two factors. The highest mean birth rate (10.8 +/- 2.1%) was
      obtained with (B6 x 129)F1 Sertoli cells. In the second series of experiments, we
      examined whether the developmental ability of clones with the wild-type genotype
      (JF1) was improved when combined with the 129 genotype. Normal pups were cloned
      from cumulus and immature Sertoli cells of the (129 x JF1)F1 and (JF1 x 129)F1
      genotypes, whereas no pups were born from cells with the (B6 x JF1)F1 genotype.
      The present study clearly demonstrates that the efficiency of somatic cell
      cloning, and in particular fetal survival after embryo transfer, may be improved
      significantly by choosing the appropriate combinations of cell type and genotype.

PMID- 12801985
TI  - Tumor necrosis factor alpha in the bovine oviduct during the estrous cycle:
      messenger RNA expression and effect on secretion of prostaglandins, endothelin-1,
      and angiotensin II.
AB  - Tumor necrosis factor (TNF) alpha is an important physiological mediator of cell
      to-cell communication. Recent observations suggest that TNFalpha is involved in
      the control of reproductive functions. The present study examined the role of
      TNFalpha in the secretion of factors involved in regulating smooth muscle
      contraction, such as prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha),
      endothelin-1 (ET-1), and angiotensin II (Ang II), as it was in the original by
      the cow oviduct at different stages of the estrous cycle using an in vitro
      microdialysis system. Expression of mRNA for TNFalpha and its receptors (TNFalpha
      R) was also evaluated. For microdialysis, the lumen of a portion (length, 10 cm)
      of the each oviductal segment was implanted with a dialysis capillary membrane,
      and TNFalpha (100 ng/ml) was infused for 4-8 h during a 16-h incubation period.
      The microdialysis system maintains cell-to-cell integrity and cell-to-cell
      communication, and it enables real-time observation of physiological changes in
      the luminal release of different substances. Concentrations of PG, ET-1, and Ang
      II in 4-h fractions were measured using second-antibody enzyme immunoassays.
      Infusion of TNFalpha stimulated oviductal secretion of PG, ET-1, and Ang II
      during the follicular and postovulatory stages, but not during the luteal stage.
      Expression of TNFalpha, TNFalpha-R type I, and TNFalpha-R type II mRNA was
      detected in the bovine oviduct by reverse transcription-polymerase chain
      reaction. High expression of both TNFalphaR types and ligands was detected during
      the follicular and postovulatory stages, whereas low expression was detected
      during the luteal stage. The results of the present study provide, to our
      knowledge, the first direct evidence that TNFalpha stimulates PG, ET-1, and Ang
      II secretion and that up-regulation of the TNFalpha system occurs in the cow
      oviduct during the periovulatory period. In conclusion, the TNFalpha system may
      optimize the release of contraction-related substances and modulate local
      contraction to regulate the oviductal transport of the gametes and embryo.

PMID- 12801986
TI  - Mimicking the events of menstruation in the murine uterus.
AB  - Menstruation and endometrial regeneration occur during every normal reproductive
      cycle in women and some Old World primates. Many of the cellular and molecular
      events of menstruation have been identified by correlative or in vitro studies,
      but the lack of a convenient model for menstruation in a laboratory animal has
      restricted functional studies. In this study, a mouse model for menstruation
      first described by Finn in the 1980s has been modified for use in a commonly used
      inbred strain of mouse. A decidual stimulus was applied into the uterine lumen of
      appropriately primed mice and leukocyte numbers and apoptosis were examined over
      time following progesterone withdrawal. Endometrial tissue breakdown was
      initiated after 12-16 h, and by 24 h, the entire decidual zone had been shed. Re
      epithelialization was nearly complete by 36 h and the endometrium was fully
      restored by 48 h. Leukocyte numbers increased significantly in the basal zone by
      12 h after progesterone withdrawal, preceding stromal destruction. Stromal
      apoptosis was detected by TUNEL staining at 0 and 12 h but decreased by 16 h
      after progesterone withdrawal. This mouse model thus mimics many of the events of
      human menstruation and has the potential to assist in elucidation of the
      functional roles of a variety of factors thought to be important in both
      menstruation and endometrial repair.

PMID- 12801987
TI  - Fine structural cytochemical analysis of homologous chromosome recognition,
      alignment, and pairing in Guinea pig spermatogonia and spermatocytes.
AB  - The nuclei of guinea pig spermatogonia and spermatocytes were studied by means of
      quantitative autoradiography and electron microscopic methods such as high
      resolution cytochemistry, immunocytochemistry, and in situ hybridization. Our
      observations reveal, in the nucleus of spermatogonia type B, small lampbrush
      structures of extended chromatin not found in nonmeiotic cells. During meiotic
      interphase, pairs of parallel lampbrush structures become associated by numerous
      filaments. The formation of the synaptonemal complex is simultaneous with the
      extension of chromosomal axes in a continuous leptotene-zygotene stage. Some
      chromosomes do not recognize their homologs before the onset of the leptotene
      zygotene stage and undergo classical leptotene and zygotene stages. The
      immunocytochemical localization of Dmc1 and Rad51 supports the idea that these
      proteins are not involved in homology search and final pairing.
      Immunolocalization of DNA, RNA polymerase II, heterogeneous nuclear
      ribonucleoproteins, small nuclear ribonucleoproteins, and the trimethyl-guanosin
      cap of small nuclear RNAs suggests that the chromatin of lampbrush structures
      transcribe hnRNA and that splicing is scarce. The results of quantitative
      autoradiography after [3H]uridine labeling show an intense transcription
      accompanied by a very slow export of RNA. In situ hybridization demonstrates the
      presence of RNA in the regions of homology recognition and pairing. These results
      lead us to propose that the RNA synthesized in the lampbrush structures is
      involved in the process of homology searching and recognition.

PMID- 12801988
TI  - Evidence that gonadotropin-releasing hormone (GnRH) II stimulates luteinizing
      hormone and follicle-stimulating hormone secretion from monkey pituitary cultures
      by activating the GnRH I receptor.
AB  - Mammalian gonadotropin-releasing hormone (GnRH) I is the neuropeptide that
      regulates reproduction. In recent years, a second isoform of GnRH, GnRH II, and
      its highly selective type II GnRH receptor were cloned and identified in monkey
      brain, but its physiological function remains unknown. We sought to determine
      whether GnRH II stimulates LH and FSH secretion by activating specific receptors
      in primary pituitary cultures from male monkeys. Dispersed pituitary cells were
      maintained in steroid-depleted media and stimulated with GnRH I and/or GnRH II
      for 6 h. Cells were also treated with Antide (Bachem, King of Prussia, PA), a
      GnRH I antagonist, to block gonadotropin secretion. In monkey as well as rat
      pituitary cultures, GnRH II was a less effective stimulator of LH and FSH
      secretion than was GnRH I. In both cell preparations, Antide completely blocked
      LH and FSH release provoked by GnRH II as well as GnRH I. Furthermore, the
      combination of GnRH I and GnRH II was no more effective than either agonist
      alone. These results indicate that GnRH II stimulates FSH and LH secretion, but
      they also imply that this action occurs through the GnRH I receptor. The GnRH II
      receptors may have a unique function in the monkey brain and pituitary other than
      regulation of gonadotropin secretion.

PMID- 12801989
TI  - Dramatic expansion of germinal stem cells by ectopically expressed human glial
      cell line-derived neurotrophic factor in mouse Sertoli cells.
AB  - Although the mammalian germinal stem cell (GSC) provides a good model to
      investigate the regulation of stem cells, the small number of these cells
      currently available hampers elucidation of the regulatory mechanism. Here, we
      show the dramatic amplification of GSCs in mouse testis following transfection of
      human glial cell line-derived neurotrophic factor cDNA into Sertoli cells using
      an efficient, in vivo electroporation technique. Transplantation analysis
      demonstrated not only GSC enrichment but also differentiation from stem cells
      into sperm. The GSC population, as estimated using a colony-formation assay, was
      approximately 20-fold greater than in cryptorchid testis, or approximately 500-
      to 1000-fold greater than in normal adult testis. This system should provide
      sufficient quantities of GSCs to accelerate our understanding of GSC properties,
      regulation mechanisms, and behavior control.

PMID- 12801990
TI  - Characterization of the interleukin-1beta system during porcine trophoblastic
      elongation and early placental attachment.
AB  - Conceptus-uterine communication is established during trophoblastic elongation
      when the conceptus synthesizes and releases estrogen, the maternal recognition
      signal in the pig. Interleukin-1beta (IL-1beta) is a differentially expressed
      gene during rapid trophoblastic elongation in the pig. The current investigation
      determined conceptus and endometrial changes in gene expression for IL-1beta, IL
      1 receptor antagonist (IL-1Rant), IL-1 receptor type 1 (IL-1RT1), and IL-1
      receptor accessory protein (IL-1RAP) in developing peri- and postimplantation
      conceptuses as well as uterine endometrium collected from cyclic and pregnant
      gilts. Conceptus IL-1beta gene expression was enhanced during the period of rapid
      trophoblastic elongation compared with earlier spherical conceptuses, followed by
      a dramatic decrease in elongated Day 15 conceptuses. IL-1RT1 and IL-1RAP gene
      expression was greater in Day 12 and 15 filamentous conceptuses compared with
      earlier morphologies while IL-1Rant gene expression was unchanged by conceptus
      development. The uterine lumenal content of IL-1beta increased during the process
      of trophoblastic elongation on Day 12. Uterine IL-1beta content declined on Day
      15, reaching a nadir by Day 18 of pregnancy. IL-1beta gene expression in porcine
      conceptuses was temporally associated with an increase in endometrial IL-1RT1 and
      IL-1RAP gene expression in pregnant gilts. Endometrial IL-1beta and IL-1Rant gene
      expression were lowest during Days 10-15 of the estrous cycle and pregnancy. The
      temporal expression of IL-1beta during conceptus development and the initiation
      of conceptus-uterine communication suggests conceptus IL-1beta synthesis plays an
      important role in porcine conceptus elongation and the establishment of pregnancy
      in the pig.

PMID- 12801991
TI  - Changes in the expression of calcitonin receptor-like receptor, receptor activity
      modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy,
      labor, and by steroid hormone treatments.
AB  - Calcitonin gene-related peptide (CGRP) and its related peptide, adrenomedullin
      (AM), are potent smooth muscle relaxants in a variety of tissues. The CGRP has
      been reported to play an important role in maintaining uterine relaxation during
      pregnancy. We have previously reported that CGRP-induced uterine relaxation was
      gestationally regulated. Calcitonin receptor-like receptor (CRLR), a seven-domain
      transmembrane protein functions as CGRP-A receptor, in association with receptor
      activity-modifying protein (RAMP) 1, a single-domain transmembrane protein,
      whereas CRLR and RAMP2 or RAMP3 constitute a receptor for AM. In the present
      investigation, we examined the mRNA expression of CRLR, RAMP1, RAMP2, and RAMP3
      in rat uterus (n = 8) by reverse transcriptional analysis and polymerase chain
      reaction to assess the changes in the expression of CGRP-A- and AM-receptor
      components during pregnancy and labor and by steroid hormone treatments in adult
      ovariectomized rats. The changes in mRNA are expressed relative to the 18S mRNA
      in the uterus of rats at various stages: nonpregnant, pregnant on Day 18,
      spontaneous labor at term, Day 2 postpartum, and in pregnant rats on treatment
      with RU486. Ovariectomized rats treated for 3 days twice daily s.c. with
      estradiol-17beta (2.5 microg/injection), progesterone (2 mg/injection), and the
      combination of estradiol-17beta and progesterone (same doses as above) were also
      examined for the expression of various receptor components. Results showed that
      mRNA expression of the receptor components was significantly higher (P < 0.001
      for CRLR, P < 0.01 for RAMP1, P < 0.05 for RAMP2, and P < 0.01 for RAMP3) in
      pregnant compared to nonpregnant rats. Except for RAMP3, expression of all the
      other three genes decreased significantly (P < 0.05) during labor. A progesterone
      antagonist, RU486 significantly decreased (P < 0.01 for CRLR, P < 0.05 for RAMP1,
      RAMP2, and RAMP3) all the receptor components during pregnancy. In adult
      ovariectomized rats, progesterone caused significant increases in CRLR (P <
      0.001), RAMP1 (P < 0.05), and RAMP2 (P < 0.01). Levels of RAMP3 were unaffected
      by the progesterone treatment. Estradiol-17beta treatment decreased all of the
      four receptor components significantly (P < 0.01 for CRLR, P < 0.05 for RAMP1,
      RAMP2, and RAMP3). Our results demonstrate that both CGRP and AM may play a role
      in uterine quiescence during pregnancy and that their receptor components are
      regulated by the steroid hormones.

PMID- 12801992
TI  - Developmental and molecular aberrations associated with deterioration of
      oogenesis during complete or partial follicle-stimulating hormone receptor
      deficiency in mice.
AB  - Targeted disruption of the mouse FSH receptor gene (FSH-R) that mediates the
      action of the FSH results in a gene dose-related ovarian phenotype in the
      developing as well as the adult animal. While null females (FORKO) are sterile,
      the haplo-insufficient mice experience early reproductive senescence. The purpose
      of this study was to first record changes in oocyte development in the null FORKO
      and haplo-insufficient mice. Oocyte growth is significantly retarded in the null
      mutants with thinner zona pellucida in preantral follicles, but thicker zona
      pellucida in secondary follicles. This morphometric change indicates
      developmental aberrations in coordination of the germ cell (oocyte) and the
      somatic granulosa cell (GC) compartments. Markers for primordial germ cell
      proliferation and oocyte growth, such as the c-Kit/Kit-ligand and bone
      morphogenetic protein-15 (BMP-15) were downregulated in both null and +/-
      ovaries, suggesting disrupted communication between oocyte and GCs. Extensive
      changes in the expression of other oocyte-specific gene products like the zona
      pellucida glycoproteins (zona pellucida A, B, and C) indicate major alteration in
      the extracellular matrix surrounding the germ cells. This led to leaky germ cells
      that allowed infiltration of somatic cells. These results show that the loss of
      FSH-R signaling alters the follicular environment, where oocyte-granulosa
      interactions are perturbed, creating an out-of-phase germ cell and somatic cell
      development. We believe that these data provide an experimental paradigm to
      explore the mechanisms responsible for preserving the structural integrity and
      quality of oocytes at different ages.

PMID- 12801993
TI  - Dynamics of ovarian development in the FORKO immature mouse: structural and
      functional implications for ovarian reserve.
AB  - Adult Follitropin Receptor Knockout (FORKO) female mice are infertile and
      estrogen deficient. In order to understand the peri/postnatal developmental
      changes, we have now characterized the structural and molecular aberrations by
      comparing several markers of follicular development in 2-, 10-, and 24-day-old
      wild-type and FORKO females. By Day 24, FORKO mice have 40%-50% smaller uteri and
      vaginas. Estradiol is undetectable but testosterone and LH levels are already
      elevated at this age. FORKO ovaries are 45% smaller, indicating a postnatal or
      perinatal deficit consequent to FSH receptor ablation. This is attributable to
      decreased numbers of growing follicles and reduced diameter. Developmental
      markers, such as Mullerian inhibiting substance, GATA-4, estrogen receptor beta,
      and androgen receptor, were differentially expressed in granulosa cells. In the 2
      day-old mutant neonates, a faster recruitment process was noted that later slowed
      down, impeding development of follicles. This is noteworthy in light of the
      controversy regarding the direct role of FSH/receptor system as a determinant of
      small and preantral follicle development in rodents. As the pool of nongrowing
      primordial follicles specifies the duration of female fertility and timing of
      reproductive senescence, we believe that the postnatal FORKO female mouse could
      help in exploring the signals that impact on early folliculogenesis. In addition,
      our data suggest that the FSH/receptor system is a major contributor to the
      formation and recruitment of the nongrowing pool of follicles as early as
      Postnatal Day 2 in the mouse.

PMID- 12801994
TI  - Sp1 and Sp3 Are important regulators of AP-2gamma gene transcription.
AB  - AP-2gamma is a member of the AP-2 transcription factor family, is highly enriched
      in the trophoblast cell lineage, and is essential for placental development. In
      an effort to identify factors regulating AP-2gamma gene expression, we isolated
      and characterized the promoter and 5'-flanking region of the mouse and human AP
      2gamma genes. The transcription start site of the mouse AP-2gamma gene was mapped
      by primer extension and 5' rapid amplification of cDNA ends. Deletion analysis of
      the 5'-flanking region revealed a 704-base pair (bp) sequence located
      approximately 6 kilobases (kb) upstream of the transcription start site that is
      required for enhanced expression in trophoblast cells. Additional gene transfer
      studies showed that basal promoter activity resides within a highly conserved,
      approximately 200-bp DNA sequence located immediately upstream of the
      transcription start site. The conserved region is highly GC-rich and lacks
      typical TATA or CCAAT boxes. Multiple potential Sp- and AP-2-binding sites are
      clustered within this region. Electrophoretic mobility shift assays demonstrated
      that Sp1 and Sp3 bind to three sites in the promoter region of the mouse AP
      2gamma gene. Combined mutation of the three putative Sp sites reduced promoter
      activity by 80% in trophoblast and nontrophoblast cells, demonstrating the
      functional importance of these sites in regulating AP-2gamma gene expression. In
      summary, we have identified a potential trophoblast cell-specific regulatory
      element located approximately 6 kb upstream of the murine AP-2gamma gene
      transcription start site, and we have shown that Sp1 and Sp3 bind to cis
      regulatory elements located in the promoter proximal region and contribute to
      basal promoter activity.

PMID- 12801996
TI  - Reduced intrafollicular androstenedione and estradiol levels in early-treated
      prenatally androgenized female rhesus monkeys receiving follicle-stimulating
      hormone therapy for in vitro fertilization.
AB  - Five early-treated and four late-treated prenatally androgenized and five normal
      female rhesus monkeys were studied to determine whether prenatal testosterone
      propionate exposure beginning Gestational Days 40-44 (early-treated) or 100-115
      (late-treated) affects follicular steroidogenesis during recombinant human FSH
      (rhFSH) treatment. All monkeys underwent rhFSH injections, without human
      chorionic gonadotropin administration, followed by oocyte retrieval. Serum FSH,
      LH, estradiol (E2), progesterone (P), 17alpha-hydroxyprogesterone (17 OHP),
      androstenedione (A4), testosterone, and dihydrotestosterone were measured basally
      during rhFSH therapy and at oocyte retrieval. Follicle fluid (FF) sex steroids,
      oocyte fertilization, and embryo development were analyzed. Circulating FSH, E2,
      17 OHP, A4, and dihydrotestosterone levels increased similarly in all females.
      Serum LH levels decreased from basal levels in normal and late-treated prenatally
      androgenized females but were unchanged in early-treated prenatally androgenized
      females. Serum P levels at oocyte retrieval were comparable with those before FSH
      treatment in all females. All prenatally androgenized females showed reduced FF
      levels of A4 and E2 but not P or dihydrotestosterone. Intrafollicular T
      concentrations also were significantly lower in late-treated compared with early
      treated prenatally androgenized females or normal females. In early-treated
      prenatally androgenized females, but not the other female groups, intrafollicular
      A4 and E2 levels were reduced in follicles containing oocytes that failed
      fertilization or produced zygotes with cleavage arrest before or at the five- to
      eight-cell embryo stage. Therefore, in monkeys receiving rhFSH therapy alone
      without human chorionic gonadotropin administration, early prenatal
      androgenization reduced FF concentrations of E2 and A4 in association with
      abnormal oocyte development, without having an effect on P, testosterone, or
      dihydrotestosterone concentrations.

PMID- 12801995
TI  - Gene expression profiling of the effects of castration and estrogen treatment in
      the rat uterus.
AB  - The development and functions of female reproductive tissues are regulated by the
      actions of two major sex steroid hormones, estrogen and progesterone. To
      investigate estrogen-dependent gene expression in the rat uterus, we studied the
      effect of ovariectomy with or without estrogen treatment on the uterine
      expression of 3000 genes using cDNA microarrays. Many genes were regulated by
      either treatment, but only few were reciprocally regulated by these contrasting
      treatments. The present study confirms previous findings and identifies several
      genes with expressions not previously known to be influenced by estrogen. These
      genes include follistatin-related protein, Thy-1 glycoprotein, alpha-fodrin,
      CD24, immediate early response 5, insulin-like growth factor-binding protein 2,
      growth response protein CL-6 (INSIG-1), ladinin1, class I major
      histocompatibility complex heavy chain, lactadherin, ezrin, and Fas-activated
      serine/threonine kinase. Because of their function as regulators of proliferation
      and apoptosis, CD24, insulin-like growth factor-binding protein 2, and Fas/Fas
      ligand were examined further by immunohistochemical expression and tissue
      localization analysis. Our analysis confirms a contrasting regulation of these
      gene products by ovariectomy and estrogen treatment. The present study identifies
      novel mediators of estrogen actions in the uterus and provides genome-wide
      expression data from which novel hypotheses regarding uterine function can be
      generated.

PMID- 12801997
TI  - Mechanisms of action of transforming growth factor beta on the expression of
      follicle-stimulating hormone receptor messenger ribonucleic acid levels in rat
      granulosa cells.
AB  - The present study was undertaken to identify the mechanisms underlying the effect
      of transforming growth factor (TGF) beta on FSH receptor (FSH-R) in rat granulosa
      cells. Compared to the control, the treatment of granulosa cells with TGFbeta (10
      ng/ml) increased FSH-R mRNA transcripts (5.5 and 2.4 kilobases) in a time
      dependent manner, with a maximum increase of approximately 2-fold at 48 h. We
      then investigated whether the effect of TGFbeta on FSH-R mRNA levels was the
      result of increased transcription and/or altered mRNA stability. To determine
      whether the FSH-R 5'-flanking region plays a role in directing FSH-R mRNA
      expression, the proximal area of the FSH-R 5'-flanking regions were inserted into
      an expression vector, pGL-Basic, which contains luciferase as the receptor gene,
      and the resulting plasmids were transiently transfected into rat granulosa cells.
      The FSH (30 ng/ml) significantly enhanced the activity of 1862 base pairs of the
      FSH-R 5'-flanking region, but treatment with TGFbeta did not significantly
      influence the activity induced by FSH. On the other hand, the decay curves for
      FSH-R mRNA transcript in primary granulosa cells showed a significant increase in
      half-life after the addition of TGFbeta. Transforming growth factor beta
      stimulates the expression of follistatin mRNA accumulation in a dose- and time
      dependent manner. Treatment with activin produced a substantial increase in FSH-R
      mRNA level. Concurrent treatment with follistatin neutralized this activin effect
      on FSH-R mRNA, as reported, although concurrent treatment with follistatin did
      not affect TGFbeta-induced FSH-R mRNA. Therefore, the profile of the TGFbeta
      effect on FSH-R mRNA granulosa cells may be caused by the increased stability of
      FSH-R mRNA and insensitivity to the follistatin.

PMID- 12801998
TI  - Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and
      correlates with severe spermatozoan head and midpiece malformation, impaired
      binding to the zona pellucida, and oocyte penetration.
AB  - The members of the nectin/CD155 gene family represent a growing class of novel
      cell adhesion molecules of the immunoglobulin superfamily. In the present study,
      we describe the generation of a mouse line lacking a functional nectin-2 gene
      (nectin-2LacZ/LacZ) and analyze the resulting male-specific infertility
      phenotype. Although nectin-2LacZ/LacZ males produced normal amounts of motile
      spermatozoa, scanning electron microscopy revealed severe malformations of the
      spermatozoan head and midpiece. Besides a 4-fold reduction in migration of nectin
      2LacZ/LacZ spermatozoa to the oviducts, in vitro binding to zona-intact mouse
      oocytes was reduced 6-fold. On the other hand, nectin-2LacZ/LacZ spermatozoa
      bound to zona-free hamster oocytes at near-wild type levels but, remarkably,
      failed to penetrate. In addition to the previously reported expression of nectin
      2 and nectin-3 at Sertoli-spermatid junctions and of nectin-2 at inter-Sertoli
      cell junctions, we also found nectin-2 to localize at apical cell-cell junctions
      of the epididymal epithelium. Expression analysis of a LacZ knockin gene into the
      defunct nectin-2 gene in nectin-2LacZ/LacZ mice provided additional support for
      our earlier conjecture that in normal testis, nectin-2 is produced exclusively by
      Sertoli cells. Finally, we found Sertoli-spermatid junctions in nectin-2LacZ/LacZ
      mice to be virtually devoid of the actin-bundling protein espin, suggesting that
      ectoplasmic specializations fail to form in the absence of nectin-2. Our
      functional analyses indicate that the infertility phenotype of nectin-2-deficient
      male mice is caused by a combination of reduced migration to the oviduct,
      spermatozoa-zona binding, and sperm-oocyte fusion. We corroborate our previous
      description of a heterotypic adhesion complex between Sertoli cells and elongated
      spermatids that is maintained by nectin-2 and nectin-3, respectively.

PMID- 12801999
TI  - In vitro MR imaging of regulated gene expression.
AB  - PURPOSE: To design and evaluate a construct that allows regulated expression of
      the magnetic resonance (MR) imaging reporter gene human tyrosinase under control
      of the tetracycline response element. MATERIALS AND METHODS: A breast cancer cell
      line (MCF-7) was transfected with a plasmid that codes for the tetracycline
      controlled transactivator and a new construct. In this construct, the reporter
      gene human tyrosinase is under control of the tetracycline response element, thus
      allowing suppression of gene expression by adding doxycycline (tetracycline
      switched off). A reverse transcription polymerase chain reaction was conducted to
      evaluate gene expression. Additionally, immunohistochemical investigation of
      tyrosinase and melanin staining was undertaken to analyze the presence of these
      molecules. After culture in an iron- and holotransferrin-enriched medium, cells
      were imaged in a 1.0-T clinical MR imager by using a surface coil and T1-weighted
      spin-echo and gradient-echo sequences. RESULTS: Two stable transfected cell
      clones were established. Cells cultured with doxycycline showed no background
      expression of the human tyrosinase gene, whereas withdrawal of doxycycline
      resulted in detectable tyrosinase messenger RNA expression. Gene expression
      results in a detectable tyrosinase protein level and melanin content. Increased
      signal intensity on T1-weighted MR images in cells that expressed the reporter
      gene was observed in comparison to genetically identical cells with the reporter
      gene switched off. CONCLUSION: Our construct enables MR imaging of regulated
      tyrosinase gene expression in vitro.

PMID- 12802000
TI  - Quantitative CT indexes in idiopathic pulmonary fibrosis: relationship with
      physiologic impairment.
AB  - PURPOSE: To determine whether measurements of skewness, kurtosis, and mean lung
      attenuation on thin-section computed tomographic (CT) histograms in patients with
      idiopathic pulmonary fibrosis (IPF) correlate with pulmonary physiologic
      abnormality in a nonspirometrically controlled multicenter study. MATERIALS AND
      METHODS: The authors analyzed baseline digital thin-section CT data from 144
      patients with IPF who enrolled in a double-blind placebo-controlled clinical
      effectiveness trial of interferon beta 1a in the treatment of IPF. All patients
      underwent thin-section CT in the supine position at full inspiration. The lungs
      were isolated by using a semiautomated thresholding technique, with an upper
      threshold of -200 HU. An attenuation correction algorithm was used. Pulmonary
      function tests (PFTs) included forced vital capacity, total lung capacity, forced
      expiratory volume in 1 second, and diffusing lung capacity. Univariate and
      multiple correlation and regression statistical analyses were used to determine
      relationships between histogram features and results of PFTs. RESULTS: Moderate
      correlations existed between histogram features and PFT results. Kurtosis showed
      the greatest degree of correlation with physiologic abnormality (r = 0.53, P
      <.01). Strength of correlation increased with exclusion of suboptimal scans but
      did not change significantly after application of an attenuation correction
      algorithm. Attenuations for lungs, gas, and soft tissue varied considerably
      between scanner manufacturers. Kurtosis alone provided predictions of pulmonary
      function that were virtually as good as those from all histogram features
      combined. CONCLUSION: Thin-section CT histograms of the lungs were found to
      correlate with results of PFTs in patients with IPF, which supports the claim
      that histogram features can be used as valid indexes of IPF in a
      multiinstitutional nonspirometrically controlled study.

PMID- 12802001
TI  - Clinically suspected constrictive pericarditis: MR imaging assessment of
      ventricular septal motion and configuration in patients and healthy subjects.
AB  - PURPOSE: To assess ventricular septal motion and quantify the septal
      configuration in patients clinically suspected of having constrictive
      pericarditis (CP), and to compare these patients with healthy subjects and with
      patients who have other diastolic heart abnormalities such as restrictive
      cardiomyopathy (RCM). MATERIALS AND METHODS: In 41 patients clinically suspected
      of having CP and 12 healthy subjects, magnetic resonance (MR) imaging yielded
      information about cardiac morphology and function. On short-axis cine MR images,
      septal motion was assessed, and the septal and left ventricular free wall (LVFW)
      radii of curvature were quantified and normalized to end systole. Abnormal
      diastolic septal motion was expressed in terms of the largest difference in
      normalized radius between the septum and the LVFW. Analysis of variance was used
      to identify significant differences in septal shape among subject groups.
      RESULTS: Left-sided septal flattening was identified in 17 of the 21 patients
      with surgically proven CP, in none of the 20 patients without CP, and in none of
      the healthy subjects. CP without septal flattening was present on the left side
      (n = 1), on the right side (n = 1), and at the atrioventricular grooves (n = 2).
      Abnormal septal motion yielded a sensitivity of 81% (17 of 21 patients),
      specificity of 100% (20 of 20 patients), accuracy of 90% (37 of 41 patients),
      positive predictive value of 100% (17 of 17 patients), and negative predictive
      value of 83% (20 of 24 patients) in the detection of CP. The maximal difference
      in normalized radius of curvature between the septum and the LVFW in the patients
      with CP was significantly different from that in the patients without CP (P
      <.001) and that in the healthy subjects (P <.001). CONCLUSION: Abnormal diastolic
      septal motion is a frequent phenomenon of CP. If present in patients suspected of
      having CP, this finding is helpful in distinguishing CP from RCM.

PMID- 12802002
TI  - Trigeminal neuralgia: evaluation of neuralgic manifestation and site of
      neurovascular compression with 3D CISS MR imaging and MR angiography.
AB  - PURPOSE: To evaluate three-dimensional (3D) constructive interference in steady
      state (CISS) magnetic resonance (MR) imaging and MR angiography with multiplanar
      reconstruction (MPR) for detection of neurovascular compression (NVC) in patients
      with trigeminal neuralgia and to evaluate the relationship between clinical
      symptoms related to trigeminal branches and those related to the site of
      trigeminal nerve compression. MATERIALS AND METHODS: Fifty-four consecutive
      patients with trigeminal neuralgia were examined at 3D CISS imaging and MR
      angiography with a 1.5-T MR system. Original transverse and four reformatted
      images were used for image interpretation. Vascular contact with the trigeminal
      nerve at the root entry zone (REZ) was determined, and the nature of the involved
      vessels was identified. The position of the blood vessel compressing the nerve
      was classified into cranial, caudal, medial, or lateral sites. Statistical
      analysis was performed with the chi2 test or the Fisher exact test between two
      groups and with the chi2 test among more than two groups. RESULTS: In 12 of 15
      patients who underwent surgery, the artery that was considered a responsible
      vessel at 3D CISS imaging and MR angiography was confirmed as such. In the other
      three patients, the vein was the responsible vessel, which was detected only at
      3D CISS imaging. Sixteen (89%) of 18 patients with symptoms related to the
      maxillary division had NVC at the medial site of the REZ, while 16 (76%) of 21
      patients with symptoms related to the mandibular division had NVC at the lateral
      site (P <.001, chi2 test). CONCLUSION: 3D CISS MR imaging with MPR is useful in
      the detection of NVC in patients with trigeminal neuralgia, compared with MR
      angiography. A close relationship was found between the region of neuralgic
      manifestation and the site of trigeminal nerve compression.

PMID- 12802003
TI  - Blood flow quantification with contrast-enhanced US: "entrance in the section"
      phenomenon--phantom and rabbit study.
AB  - PURPOSE: To investigate changes in destruction-replenishment curves (in vitro and
      in vivo) that result from microbubble destruction in feeding vessels that pass
      through the imaging plane before microbubbles enter the region of interest (ROI).
      MATERIALS AND METHODS: During continuous injections of an ultrasonographic
      contrast agent, nonlinear gray-scale images were obtained in vitro in the
      longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100,
      200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two
      rabbits (two kidneys). Destruction-replenishment curves were obtained for the
      dialysis cartridge in ROIs located immediately after the entrance of the
      microbubbles into the image plane and further from the entrance, after
      microbubbles had traveled across the complete length of the imaging plane.
      Replenishment curves were also obtained from ROIs in the rabbit kidneys at the
      level of segmental arteries, distal interlobar arteries, and the cortex. RESULTS:
      The ROIs immediately after the entrance of the microbubbles in the image plane of
      the dialysis cartridge and in the segmental artery of the kidney followed a
      typical exponential function, A(1 - e-alphat). Early portions of curves obtained
      in ROIs filled with microbubbles that had already passed through the image plane
      of the dialysis cartridge or in the renal cortex were not well described by such
      a function. The shape of the curve and the variations as a function of flow rate
      can be explained by means of a mathematical model based on indicator-dilution
      theory. CONCLUSION: When the feeding vessels of an ROI travel across the
      ultrasound field before they reach the measurement region, the typical shape of
      the replenishment curve is modified (reduced velocity parameter and plateau).

PMID- 12802004
TI  - MR imaging findings in spinal infections: rules or myths?
AB  - PURPOSE: To systematically evaluate magnetic resonance (MR) imaging findings
      described as being indicative of spinal infection in patients with proven spinal
      infection. MATERIALS AND METHODS: Contrast material-enhanced spinal MR images
      obtained in 46 consecutive patients (22 women, 24 men; mean age, 58.2 years) with
      culture or histologic examination results positive for spinal infection were
      systematically evaluated by two observers. Tuberculous and postoperative
      infections were excluded. Disk signal intensity and disk height, presence of the
      nuclear cleft, vertebral signal intensity alterations, endplate erosions on T1
      weighted MR images, and presence of paraspinal or epidural inflammation were
      evaluated. Patient charts and surgical reports were reviewed. RESULTS: In the 44
      patients with disk infection, MR imaging criteria with good to excellent
      sensitivity included presence of paraspinal or epidural inflammation (n = 43,
      97.7% sensitivity), disk enhancement (n = 42, 95.4% sensitivity), hyperintensity
      or fluid-equivalent disk signal intensity on T2-weighted MR images (n = 41, 93.2%
      sensitivity), and erosion or destruction of at least one vertebral endplate (n =
      37, 84.1% sensitivity). Effacement of the nuclear cleft was only applicable in 18
      patients (n = 15, 83.3% sensitivity). Criteria with low sensitivity included
      decreased height of the intervertebral space (n = 23, 52.3% sensitivity) and disk
      hypointensity on T1-weighted MR images (n = 13, 29.5% sensitivity). Involvement
      of several spinal levels occurred in seven (16%) patients. Other spinal
      infections included isolated vertebral osteomyelitis (n = 1) and primary epidural
      abscess (n = 1). CONCLUSION: Most MR imaging criteria commonly used to diagnose
      disk infections offer good to excellent sensitivity. In atypical manifestations
      of proven spinal infections, however, some of the classically described MR
      imaging criteria may not be observed.

PMID- 12802005
TI  - Atrial septal defects in pediatric patients: noninvasive sizing with
      cardiovascular MR imaging.
AB  - PURPOSE: To evaluate phase-contrast magnetic resonance (MR) imaging for sizing of
      secundum atrial septal defects (ASDs) and inflow MR angiography for detection of
      associated venous anomalies in pediatric patients with inconclusive transthoracic
      echocardiographic (TTE) results. MATERIALS AND METHODS: Sixty-five children (mean
      age, 5.4 years +/- 2.7 [SD]) with ASD and inconclusive TTE results underwent
      phase-contrast MR imaging. Defect size and rim distances measured on MR imaging
      sections obtained in the ASD plane and from the defect to the venae cavae, aortic
      root, and atrioventricular valves were compared with transesophageal
      echocardiographic (TEE) findings (n = 30) during transcatheter closure or
      surgical measurements (n = 40) by using Bland-Altman analysis. Inflow MR
      angiography was compared with invasive cine angiocardiography for detection of
      associated venous anomalies. RESULTS: For ASD size, mean differences were less
      than 1 mm between MR imaging and TEE measurements (with upper and lower limits of
      agreement between 2.3 and -3.3 mm) and were between 1.2 and -1.6 mm between MR
      imaging and surgical measurements (with upper and lower limits of agreement
      between 4.7 and -5.2 mm). Septal rim measurements at MR imaging agreed fairly
      well with TEE and surgical results. Septal length was overestimated at MR imaging
      versus TEE (mean difference, 3.0 mm; upper and lower limits of agreement, between
      8.0 and -2.8 mm), but MR imaging septal length measurements agreed with surgical
      results. Rim distance to coronary sinus was difficult to assess. MR imaging
      enabled referral of 25 of 30 patients for successful transcatheter closure; five
      patients were found to have too large defects after balloon sizing. Multiple ASDs
      and/or associated vascular anomalies in 17 of 65 patients were clearly identified
      at MR imaging, compared with results of TEE, surgery, and cardiac
      catheterization. CONCLUSION: In children with ASD and inconclusive TTE results,
      MR imaging can enable determination of defect size, rim distances to adjacent
      structures, and venous connections.

PMID- 12802006
TI  - Cost-effectiveness of PET in the diagnosis of Alzheimer disease.
AB  - PURPOSE: To evaluate the cost-effectiveness of positron emission tomography (PET)
      in the diagnosis of Alzheimer disease (AD) in community-dwelling patients with
      mild or moderate dementia who present to specialized AD centers. MATERIALS AND
      METHODS: A decision-analytic model was used to compare costs and quality-adjusted
      life years (QALYs) associated with strategies involving single photon emission
      computed tomography (SPECT), dynamic susceptibility-weighted contrast material
      enhanced magnetic resonance (MR) imaging, and PET as functional imaging adjuncts
      to the standard clinical work-up. Sensitivity analyses were performed to examine
      changes in test characteristics, health-related quality-of-life survey
      instruments, therapeutic effectiveness, and treatment rules. RESULTS: The use of
      PET to confirm the results of the standard clinical work-up cost more but yielded
      fewer benefits than a strategy in which dynamic susceptibility-weighted contrast
      enhanced MR imaging was substituted for the typically performed structural
      computed tomography. This relationship remained stable in scenarios in which
      standard diagnostic work-up accuracy, drug treatment effectiveness, and version
      of the Health Utilities Index were altered. Dynamic susceptibility-weighted
      contrast-enhanced MR imaging cost US dollars 598800 per QALY gained (range, US
      dollars 74400 to US dollars 1.9 million per QALY), compared with the cost of the
      standard diagnostic work-up. Treating all patients with dementia was the dominant
      imaging strategy, except when side effects in patients with non-AD-related
      dementia were modeled. In all scenarios, SPECT yielded fewer benefits than other
      strategies at a higher cost. CONCLUSION: PET may have high diagnostic accuracy,
      but adding it to the standard diagnostic regimen at AD clinics would yield
      limited, if any, benefits at very high costs.

PMID- 12802007
TI  - Stepwise cytoskeletal polarization as a series of checkpoints in innate but not
      adaptive cytolytic killing.
AB  - Cytolytic killing is a major effector mechanism in the elimination of virally
      infected and tumor cells. The innate cytolytic effectors, natural killer (NK)
      cells, and the adaptive effectors, cytotoxic T cells (CTL), despite differential
      immune recognition, both use the same lytic mechanism, cytolytic granule release.
      Using live cell video fluorescence microscopy in various primary cell models of
      NK cell and CTL killing, we show here that on tight target cell contact, a
      majority of the NK cells established cytoskeletal polarity required for effective
      lytic function slowly or incompletely. In contrast, CTLs established cytoskeletal
      polarity rapidly. In addition, NK cell killing was uniquely sensitive to minor
      interference with cytoskeletal dynamics. We propose that the stepwise NK cell
      cytoskeletal polarization constitutes a series of checkpoints in NK cell killing.
      In addition, the use of more deliberate progression to effector function to
      compensate for inferior immune recognition specificity provides a mechanistic
      explanation for how the same effector function can be used in the different
      functional contexts of the innate and adaptive immune response.

PMID- 12802008
TI  - Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase that can
      regulate cell survival and proliferation.
AB  - Protein tyrosine phosphatase RQ (PTPRQ) was initially identified as a protein
      tyrosine phosphatase (PTPase)-like protein that is upregulated in a model of
      renal injury. Here we present evidence that, like PTEN, the biologically
      important enzymatic activity of PTPRQ is as a phosphatidylinositol phosphatase
      (PIPase). The PIPase specificity of PTPRQ is broader than that of PTEN and
      depends on different amino acid residues in the catalytic domain. In vitro, the
      recombinant catalytic domain of PTPRQ has low PTPase activity against tyrosine
      phosphorylated peptide and protein substrates but can dephosphorylate a broad
      range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5
      trisphosphate and most phosphatidylinositol monophosphates and diphosphates.
      Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring.
      PTPRQ does not have either of the basic amino acids in the catalytic domain that
      are important for the PIPase activity of PTEN or the sequence motifs that are
      characteristic of type II phosphatidylinositol 5-phosphatases. Instead, the
      PIPase activity depends on the WPE sequence present in the catalytic cleft of
      PTPRQ, and in the "inactive" D2 domains of many dual-domain PTPases, in place of
      the WPD motif present in standard active PTPases. Overexpression of PTPRQ in
      cultured cells inhibits proliferation and induces apoptosis. An E2171D mutation
      that retains or increases PTPase activity but eliminates PIPase activity,
      eliminates the inhibitory effects on proliferation and apoptosis. These results
      indicate that PTPRQ represents a subtype of the PTPases whose biological
      activities result from its PIPase activity rather than its PTPase activity.

PMID- 12802009
TI  - Male Japanese quails with female brains do not show male sexual behaviors.
AB  - During embryonic development, gonadal steroid hormones (androgens and estrogens)
      are thought to organize the sexual differentiation of the brain in the
      heterogametic sexes of higher vertebrates (males in mammals, females in birds).
      Brain differentiation of the homogametic sexes is thought to proceed by default,
      not requiring sex hormones for sex-specific organization. In gallinaceous birds
      such as the Japanese quail, female brain organization is thought to develop via
      estrogen-dependent demasculinization of a default male brain phenotype. We
      performed male donor-to-female host (MF), female-to-male (FM), male-to-male (MM),
      and female-to-female (FF) isotopic, isochronic transplantation of the forebrain
      primordium in Japanese quail embryos before gonadal differentiation had occurred;
      brain chimeras had a forebrain (including the hypothalamus) originating
      exclusively from donor cells. MM, FF, and MF chimeras all showed sexual behavior
      governed by the genetic sex of the host. In contrast, FM chimeras (genetically
      female forebrain, all other tissues genetically male) showed no mounting and only
      rudimentary crowing behavior. Although MM, FF, MF, and FM chimeras all showed
      host-typical production of steroid hormones during embryonic life, only FM
      chimeras were hypogonadal, had atypical low levels of circulating testosterone in
      adulthood, and showed reduction (crowing) or absence (mounting) of reproductive
      behaviors. Morphological features of the medial preoptic nucleus (a sexually
      dimorphic brain area) also were not male-like in FM males. These data demonstrate
      a brain-intrinsic, genetically determined component that organizes the sex
      typical production of gonadal hormones in adulthood and call for a reevaluation
      of the mechanisms underlying brain sexual differentiation in other higher
      vertebrate species.

PMID- 12802011
TI  - Efficient biotinylation and single-step purification of tagged transcription
      factors in mammalian cells and transgenic mice.
AB  - Proteomic approaches require simple and efficient protein purification
      methodologies that are amenable to high throughput. Biotinylation is an
      attractive approach for protein complex purification due to the very high
      affinity of avidin/streptavidin for biotinylated templates. Here, we describe an
      approach for the single-step purification of transcription factor complex(es)
      based on specific in vivo biotinylation. We expressed the bacterial BirA biotin
      ligase in mammalian cells and demonstrated very efficient biotinylation of a
      hematopoietic transcription factor bearing a small (23-aa) artificial peptide
      tag. Biotinylation of the tagged transcription factor altered neither the
      factor's protein interactions or DNA binding properties in vivo nor its
      subnuclear distribution. Using this approach, we isolated the biotin-tagged
      transcription factor and at least one other known interacting protein from crude
      nuclear extracts by direct binding to streptavidin beads. Finally, this method
      works efficiently in transgenic mice, thus raising the prospect of using
      biotinylation tagging in protein complex purification directly from animal
      tissues. Therefore, BirA-mediated biotinylation of tagged proteins provides the
      basis for the single-step purification of proteins from mammalian cells.

PMID- 12802010
TI  - T-bet is required for optimal production of IFN-gamma and antigen-specific T cell
      activation by dendritic cells.
AB  - IFN-gamma is well known as the signature cytokine of CD4+ T helper 1, CD8+, and
      natural killer cells, but recent studies demonstrate that antigen-presenting
      cells, in particular dendritic cells (DCs), are another potent source for this
      proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma
      expression in CD4+ T cells, was reported recently to be expressed in human
      monocytes and myeloid DCs. In this study we investigate the role of T-bet in this
      important cell type. The development, differentiation, and activation of bone
      marrow and splenic DCs were unimpaired in mice lacking T-bet. However, T-bet was
      essential for the optimal production of IFN-gamma by both CD8alpha+ and CD8alpha-
      DCs. T-bet-deficient DCs were significantly impaired in their capacity to secrete
      IFN-gamma after both stimulation with IL-12 alone or in combination with IL-18.
      Further, T-bet-/- DCs were impaired in their ability to activate the T helper 1
      program of adoptively transferred antigen-specific T cells in vivo. The rapid up
      regulation of T-bet by IFN-gamma in DCs coupled with a function for DC-derived
      IFN-gamma in T cell activation may constitute a positive feedback loop to
      maximize type 1 immunity.

PMID- 12802013
TI  - Genes encoding putative natural killer cell C-type lectin receptors in teleostean
      fishes.
AB  - Mammalian natural killer (NK) cells are cytotoxic lymphocytes that express
      receptors specific for MHC class I molecules. The NK cell receptors belong to two
      structurally unrelated families, the killer cell Ig-like receptors and the killer
      cell C-type lectin receptors. We describe a cDNA clone derived from the bony
      (cichlid) fish Paralabidochromis chilotes and show that it encodes a protein
      related to the CD94/NK cell group 2 (NKG2) subfamily of the killer cell C-type
      lectin receptors. The gene encoding this receptor in a related species,
      Oreochromis niloticus, has a similar structure to the human CD94/NKG2 genes and
      is a member of a multigene cluster that resembles the mammalian NK cell gene
      complex. Thus, the CD94/NKG2 subfamily of NK cell receptors must have arisen
      before the divergence of fish and tetrapods and may have retained its function
      (possibly monitoring the expression of MHC class I molecules) for >400 million
      years.

PMID- 12802014
TI  - Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain
      induces granulocytic differentiation of HL60 cells.
AB  - Glycosphingolipids form glycosphingolipid signaling microdomains. Here, we report
      an unrecognized type of phosphatidylglucoside (PhGlc)-based lipid microdomain in
      HL60 cells. Treatment of cells with rGL-7, which preferentially reacts with
      PhGlc, induced differentiation of HL60 cells. This was manifested by the
      appearance of nitroblue tetrazolium-positive cells together with CD38 expression
      and c-Myc down-regulation. We determined the molecular mechanisms underlying
      early stages of signal transduction. rGL-7 treatment induced rapid tyrosine
      phosphorylation of Src family protein kinases Lyn and Hck. Reduction of
      endogenous cholesterol after application of methyl-beta-cyclodextrin suppressed
      rGL-7-stimulated tyrosine phosphorylation. Phosphorylated proteins and PhGlc
      colocalized in the Triton X-100 insoluble, light buoyant density fraction after
      sucrose gradient ultracentrifugation of HL60 cell lysates. This suggests PhGlc
      based microdomain is involved in GL-7 signaling. Ligation of known components of
      microdomains, such as sphingomyelin and ganglioside GM1, with corresponding
      antibodies failed to induce differentiation and tyrosine phosphorylation. These
      results show that PhGlc constitutes a previously undescribed lipid signaling
      domain, and the glucose residue of PhGlc is critical for organization of the
      carbohydrate-dependent signaling domain involved in cellular differentiation of
      HL60 cells.

PMID- 12802015
TI  - Direct molecular haplotyping of long-range genomic DNA with M1-PCR.
AB  - Haplotypes, combinations of several phase-determined polymorphic markers, are
      extremely valuable for studies of disease association and chromosome evolution.
      Here we describe a technique called M1-PCR (M for "multiplex" and 1 for "single
      copy DNA molecules") that enables direct molecular haplotyping of several
      polymorphic markers separated by as many as 24 kb. A genomic DNA sample first is
      diluted to approximately single-copy. The haplotype is directly determined by
      simultaneously genotyping several polymorphic markers in the same reaction with a
      multiplex PCR and base extension reaction. This approach does not rely on
      pedigree data and does not require previous amplification of the entire genomic
      region containing the selected markers.

PMID- 12802012
TI  - Origin and evolutionary process of the CNS elucidated by comparative genomics
      analysis of planarian ESTs.
AB  - Among the bilateral animals, a centralized nervous system is found in both the
      deuterostome and protostome. To address the question of whether the CNS was
      derived from a common ancestor of deuterostomes and protostomes, it is essential
      to know kinds of genes existed in the CNS of the putative common ancestor and to
      trace the evolutionary divergence of genes expressed in the CNS. To answer these
      questions, we took a comparative approach using different species, particularly
      focusing on one of the lower bilateral animals, the planarian (Platyhelminthes,
      Tricladida), which is known to possess a CNS. We determined the nucleotide
      sequence of ESTs from the head portion of planarians, obtaining 3,101
      nonredundant EST clones. As a result of homology searches, we found that 116
      clones had significant similarity to known genes related to the nervous system.
      Here, we compared these 116 planarian EST clones with all ORFs of the complete
      genome sequences of the human, fruit fly, and nematode, and showed that >95% of
      these 116 nervous system-related genes, including genes involved in brain or
      neural morphogenesis, were commonly shared among these organisms, thus providing
      evidence at the molecular level for the existence of a common ancestral CNS.
      Interestingly, we found that approximately 30% of planarian nervous system
      related genes had homologous sequences in Arabidopsis and yeast, which do not
      possess a nervous system. This implies that the origin of nervous system-related
      genes greatly predated the emergence of the nervous system, and that these genes
      might have been recruited toward the nervous system.

PMID- 12802016
TI  - piggyBac-based insertional mutagenesis in the presence of stably integrated P
      elements in Drosophila.
AB  - P element-mediated mutagenesis has been used to disrupt an estimated 25% of genes
      essential for Drosophila adult viability. Mutation of all genes in the fly
      genome, however, poses a problem, because P elements show significant hotspots of
      integration. In addition, advanced screening scenarios often require the use of P
      element-based tools like the generation of germ-line mosaics using FLP
      recombinase-mediated recombination or gene misexpression using the UAS/Gal4
      system. These techniques are P element-based and can therefore not be combined
      with the use of P elements as mutagenic agents. To circumvent these limitations,
      we have developed an insertional mutagenesis system using non-P element
      transposons. An enhanced yellow fluorescent protein-marked piggyBac-based mutator
      element was mobilized by a piggyBac specific transposase source expressed from a
      Hermes-based jump-starter transposon marked with enhanced cyan fluorescent
      protein. In a pilot screen, we have generated 798 piggyBac insertions on FRT
      bearing third chromosomes of which 9% have sustained a putatively piggyBac
      related lethal hit. The FRTs present on the target chromosome remained stably
      integrated during the screen and could subsequently be used to generate germ-line
      clones associated with maternal and zygotic phenotypes. PCR-based analysis of
      insertion loci shows that 57% of the insertions are in genes for which no P
      element insertions have been reported. Our data demonstrate the potential of this
      technique to facilitate the quest for saturation mutagenesis of the Drosophila
      genome. The system is Drosophila nonspecific and potentially applicable in a
      broad spectrum of nonmodel organisms.

PMID- 12802017
TI  - Impairment of reward-related learning by cholinergic cell ablation in the
      striatum.
AB  - The striatum in the basal ganglia-thalamocortical circuitry is a key neural
      substrate that is implicated in motor balance and procedural learning. The
      projection neurons in the striatum are dynamically modulated by nigrostriatal
      dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal
      acetylcholine (ACh) in learning behaviors, however, remains to be fully
      clarified. In this investigation, we examine the involvement of intrastriatal ACh
      in different categories of learning by selectively ablating the striatal
      cholinergic neurons with use of immunotoxin-mediated cell targeting. We show that
      selective ablation of cholinergic neurons in the striatum impairs procedural
      learning in the tone-cued T-maze memory task. Spatial delayed alternation in the
      T-maze learning test is also impaired by cholinergic cell elimination. In
      contrast, the deficit in striatal ACh transmission has no effect on motor
      learning in the rota-rod test or spatial learning in the Morris water-maze test
      or on contextual- and tone-cued conditioning fear responses. We also report that
      cholinergic cell elimination adaptively up-regulates nicotinic ACh receptors not
      only within the striatum but also in the cerebral cortex and substantia nigra.
      The present investigation indicates that cholinergic modulation in the local
      striatal circuit plays a pivotal role in regulation of neural circuitry involving
      reward-related procedural learning and working memory.

PMID- 12802018
TI  - Allosteric control of internal electron transfer in cytochrome cd1 nitrite
      reductase.
AB  - Cytochrome cd1 nitrite reductase is a bifunctional multiheme enzyme catalyzing
      the one-electron reduction of nitrite to nitric oxide and the four-electron
      reduction of dioxygen to water. Kinetics and thermodynamics of the internal
      electron transfer process in the Pseudomonas stutzeri enzyme have been studied
      and found to be dominated by pronounced interactions between the c and the d1
      hemes. The interactions are expressed both in dramatic changes in the internal
      electron-transfer rates between these sites and in marked cooperativity in their
      electron affinity. The results constitute a prime example of intraprotein control
      of the electron-transfer rates by allosteric interactions.

PMID- 12802019
TI  - A multistep mechanism for the activation of rearrangement in the immune system.
AB  - Rearrangement of immune receptor loci is a developmentally controlled process
      that takes place exclusively in lymphoid cells. We have used a stable
      transfection system in pre-B cells to show that DNA methylation brings about
      histone underacetylation, histone H3(K9) methylation, DNaseI resistance, and
      strong inhibition of both transcription and recombination. Strikingly, this
      repression is maintained in dividing cells even after removal of the original
      methyl groups responsible for its establishment, but in this state, rearrangement
      can now be induced by reacetylation of local histones using the drug Trichostatin
      A. This same combination of demethylation and histone acetylation is also
      required to activate germline transcription and recombination from the endogenous
      kappa locus in vivo. These results indicate that the regulation of rearrangement
      is carried out by a multilayered synergistic process.

PMID- 12802020
TI  - TSG101 interaction with HRS mediates endosomal trafficking and receptor down
      regulation.
AB  - Down-regulation of mitogenic signaling in mammalian cells relies in part on
      endosomal trafficking of activated receptors into lysosomes, where the receptors
      are degraded. These events are mediated by ubiquitination of the endosomal cargo
      and its consequent sorting into multivesicular bodies that form at the surfaces
      of late endosomes. Tumor susceptibility gene 101 (tsg101) recently was found to
      be centrally involved in this process. Here we report that TSG101 interacts with
      hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), an early
      endosomal protein, and that disruption of this interaction impedes endosomal
      trafficking and endocytosis-mediated degradation of mitogenic receptors.
      TSG101/HRS interaction occurs between a ubiquitin-binding domain of TSG101 and
      two distinct proline-rich regions of HRS, and is modulated by a C-terminal TSG101
      sequence that resembles a motif targeted in HRS. Mutational perturbation of
      TSG101/HRS interaction prevented delivery of epidermal growth factor receptor
      (EGFR) to late endosomes, resulted in the cellular accumulation of ubiquitinated
      EGFR in early endosomes, and inhibited ligand-induced down-regulation of EGFR.
      Our results reveal the TSG101 interaction with HRS as a crucial step in endocytic
      down-regulation of mitogenic signaling and suggest a role for this interaction in
      linking the functions of early and late endosomes.

PMID- 12802021
TI  - Hodgkin's disease--clinical trials and travails.

PMID- 12802022
TI  - Ambulatory blood-pressure monitoring in clinical practice.

PMID- 12802023
TI  - Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone
      caproate.
AB  - BACKGROUND: Women who have had a spontaneous preterm delivery are at greatly
      increased risk for preterm delivery in subsequent pregnancies. The results of
      several small trials have suggested that 17 alpha-hydroxyprogesterone caproate
      (17P) may reduce the risk of preterm delivery. METHODS: We conducted a double
      blind, placebo-controlled trial involving pregnant women with a documented
      history of spontaneous preterm delivery. Women were enrolled at 19 clinical
      centers at 16 to 20 weeks of gestation and randomly assigned by a central data
      center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or
      weekly injections of an inert oil placebo; injections were continued until
      delivery or to 36 weeks of gestation. The primary outcome was preterm delivery
      before 37 weeks of gestation. Analysis was performed according to the intention
      to-treat principle. RESULTS: Base-line characteristics of the 310 women in the
      progesterone group and the 153 women in the placebo group were similar. Treatment
      with 17P significantly reduced the risk of delivery at less than 37 weeks of
      gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in
      the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to
      0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs.
      30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to
      0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6
      percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]).
      Infants of women treated with 17P had significantly lower rates of necrotizing
      enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.
      CONCLUSIONS: Weekly injections of 17P resulted in a substantial reduction in the
      rate of recurrent preterm delivery among women who were at particularly high risk
      for preterm delivery and reduced the likelihood of several complications in their
      infants.

PMID- 12802024
TI  - Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for
      advanced Hodgkin's disease.
AB  - BACKGROUND: Faced with unsatisfactory results of treatment for advanced Hodgkin's
      disease, we investigated three combinations of chemotherapy. METHODS: From 1993
      to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed
      Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were
      randomly assigned to receive eight cycles of cyclophosphamide, vincristine,
      procarbazine, and prednisone alternating with doxorubicin, bleomycin,
      vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or
      increased-dose BEACOPP, each followed by local radiotherapy when indicated.
      Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results.
      RESULTS: For the final analysis, 1195 of 1201 patients could be evaluated: 260 in
      the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose
      BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The
      rate of freedom from treatment failure at five years was 69 percent in the COPP
      ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose
      BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP
      group and P<0.001 for the comparison of the increased-dose BEACOPP group with the
      COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall
      survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for
      the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the
      comparison of the BEACOPP group with the increased-dose BEACOPP group, and
      P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP
      group). Rates of early progression were significantly lower with increased-dose
      BEACOPP than with COPP-ABVD or standard BEACOPP. CONCLUSIONS: Increased-dose
      BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD.

PMID- 12802025
TI  - Involved-field radiotherapy for advanced Hodgkin's lymphoma.
AB  - BACKGROUND: The use of involved-field radiotherapy after chemotherapy for
      advanced Hodgkin's lymphoma is controversial. METHODS: We randomly assigned
      patients with previously untreated stage III or IV Hodgkin's lymphoma who were in
      complete remission after hybrid chemotherapy with mechlorethamine, vincristine,
      procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP-ABV) to
      receive either no further treatment or involved-field radiotherapy. Radiotherapy
      consisted of 24 Gy to all initially involved nodal areas and 16 to 24 Gy to all
      initially involved extranodal sites. Patients in partial remission were treated
      with 30 Gy to nodal areas and 18 to 24 Gy to extranodal sites. RESULTS: Of 739
      patients, 421 had a complete remission; 161 of these patients were assigned to no
      further treatment, and 172 to involved-field radiotherapy. The median follow-up
      was 79 months. The five-year event-free survival rate was 84 percent in the group
      that did not receive radiotherapy and 79 percent in the group that received
      involved-field radiotherapy (P=0.35). The five-year overall survival rates were
      91 and 85 percent, respectively (P=0.07). Among the 250 patients in partial
      remission after chemotherapy, the five-year event-free and overall survival rates
      were 79 and 87 percent, respectively. CONCLUSIONS: Involved-field radiotherapy
      did not improve the outcome in patients with advanced-stage Hodgkin's lymphoma
      who had a complete remission after MOPP-ABV chemotherapy. Radiotherapy may
      benefit patients with a partial response after chemotherapy.

PMID- 12802026
TI  - Prognostic value of ambulatory blood-pressure recordings in patients with treated
      hypertension.
AB  - BACKGROUND: It is uncertain whether ambulatory blood-pressure measurements
      recorded for 24 hours in patients with treated hypertension predict
      cardiovascular events independently of blood-pressure measurements obtained in
      the physician's office and other cardiovascular risk factors. METHODS: We
      assessed the association between base-line ambulatory blood pressures in treated
      patients and subsequent cardiovascular events among 1963 patients with a median
      follow-up of 5 years (range, 1 to 66 months). RESULTS: We documented new
      cardiovascular events in 157 patients. In a Cox proportional-hazards model with
      adjustment for age, sex, smoking status, presence or absence of diabetes
      mellitus, serum cholesterol concentration, body-mass index, use or nonuse of
      lipid-lowering drugs, and presence or absence of a history of cardiovascular
      events, as well as blood pressure measured at the physician's office, higher mean
      values for 24-hour ambulatory systolic and diastolic blood pressure were
      independent risk factors for new cardiovascular events. The adjusted relative
      risk of cardiovascular events associated with a 1-SD increment in blood pressure
      was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory
      systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for
      ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent
      confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during
      the nighttime. For ambulatory diastolic blood pressure, the corresponding
      relative risks of cardiovascular events associated with a 1-SD increment were
      1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence
      interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40).
      CONCLUSIONS: In patients with treated hypertension, a higher ambulatory systolic
      or diastolic blood pressure predicts cardiovascular events even after adjustment
      for classic risk factors including office measurements of blood pressure.

PMID- 12802027
TI  - Itraconazole to prevent fungal infections in chronic granulomatous disease.
AB  - BACKGROUND: Chronic granulomatous disease is a rare disorder in which the
      phagocytes fail to produce hydrogen peroxide. The patients are predisposed to
      bacterial and fungal infections. Prophylactic antibiotics and interferon gamma
      have reduced bacterial infections, but there is also the danger of life
      threatening fungal infections. We assessed the efficacy of itraconazole as
      prophylaxis against serious fungal infections in chronic granulomatous disease.
      METHODS: Thirty-nine patients at least 5 years old (6 female and 33 male; mean
      age, 14.9 years) were enrolled in a randomized, double-blind, placebo-controlled
      study. After the initially assigned treatment, each patient alternated between
      itraconazole and placebo annually. Patients 13 years of age or older and all
      patients weighing at least 50 kg received a single dose of 200 mg of itraconazole
      per day; those less than 13 years old or weighing less than 50 kg received a
      single dose of 100 mg per day. The primary end point was severe fungal infection,
      as determined by histologic results or culture. RESULTS: One patient (who had not
      been compliant with the treatment) had a serious fungal infection while receiving
      itraconazole, as compared with seven who had a serious fungal infection while
      receiving placebo (P=0.10). No patient receiving itraconazole but five patients
      receiving placebo had a superficial fungal infection. No serious toxic effects
      were noted, although one patient had a rash and another had elevated results on
      liver-function tests; both of these effects resolved with the discontinuation of
      itraconazole. CONCLUSIONS: Itraconazole prophylaxis appears to be an effective
      and well-tolerated treatment that reduces the frequency of fungal infections in
      chronic granulomatous disease, but monitoring for long-term toxic effects is
      warranted.

PMID- 12802028
TI  - Images in clinical medicine. Lymphoma-associated "ivory rib".

PMID- 12802029
TI  - How can we prevent Lyme disease?

PMID- 12802030
TI  - Aromatase inhibitors in breast cancer.

PMID- 12802031
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 18-2003. A 15-year-old girl with pain in the left leg and back,
      pruritus, and thoracic lymphadenopathy.

PMID- 12802032
TI  - Progesterone and preterm delivery--deja vu all over again.

PMID- 12802033
TI  - Clinical trials and rare diseases.

PMID- 12802034
TI  - Yeast, flies, worms, and fish in the study of human disease.

PMID- 12802035
TI  - Celecoxib versus diclofenac and omeprazole to prevent recurrent ulcer bleeding.

PMID- 12802036
TI  - Aspirin and the prevention of colorectal cancer.

PMID- 12802037
TI  - Adefovir dipivoxil for hepatitis B e antigen-positive chronic hepatitis B.

PMID- 12802038
TI  - Case 9-2003: mediastinal germ-cell tumor.

PMID- 12802039
TI  - Calcified left ventricular aneurysm.

PMID- 12802040
TI  - The right to health and the nevirapine case in South Africa.

PMID- 12802041
TI  - A 20-hour treatment for acute acetaminophen overdose.

PMID- 12802042
TI  - The presenting manifestations of Lyme disease and the outcomes of treatment.

PMID- 12802043
TI  - No association between mutations in the human androgen receptor GGN repeat and
      inter-sex conditions.
AB  - The functional role of the GGN repeat in the human androgen receptor gene is
      unknown, although mutations in this region have been found in patients with inter
      sex conditions. We have investigated the prevalence of GGN mutations in the
      androgen receptor in the Swedish population and their relation to male
      reproductive function. A physical examination and semen analysis was carried out
      in 223 men under medical examination before military service and in 94 men
      referred due to infertility and having sperm concentrations <5 x 10(6)/ml. The
      GGN and CAG repeats in the androgen receptor gene were directly sequenced. Both
      populations contained two predominant alleles of 23 and 24 GGN repeats, 83.8 and
      90.5% respectively. Four mutations, three in the conscripts and one among the
      infertile men, were found, resulting in three GGC to GGT substitutions and one
      GGT to GGC substitution. None of the men presented with genital abnormalities,
      but two conscripts had low ejaculate volumes (0.3 and 0.9 ml). All men carrying a
      mutation also had GGN lengths >or=24. Three subjects with GGN >24, with no
      mutations and with normal seminal volumes, were also found. Our findings indicate
      that point mutations in the GGN repeat are frequently found in the general male
      population (1.3%; 95% CI: 0.3-3.9%), but are usually not associated with profound
      changes in the male phenotype.

PMID- 12802044
TI  - Idiopathic infertility: susceptibility of spermatozoa to in-vitro capacitation,
      in the presence and the absence of palmitylethanolamide (a homologue of
      anandamide), is strongly correlated with membrane polarity studied by Laurdan
      fluorescence.
AB  - Capacitation is a widely investigated process, which induces sperm plasma
      membrane changes resulting in its increased affinity for the zona pellucida. The
      fluorescent probe Laurdan, localized only within the plasma membrane of
      spermatozoa, is particularly useful to evaluate bilayer polarity in this part of
      the cell. According to a previous study, sperm membranes from oligozoospermic and
      some normozoospermic subjects (defined according to World Health Organization
      criteria), are characterized by low polarity (high Laurdan exGP(340)), while the
      spermatozoa from the remaining normozoospermic men show a larger polarity (low
      exGP(340)). In this paper, Laurdan was used to study membrane changes occurring
      during in-vitro capacitation, on sperm membranes from oligozoospermic and
      normozoospermic subjects. Results indicated that cells with high exGP(340) show a
      different susceptibility to Ca(2+)-induced capacitation in vitro, as compared
      with cells with low exGP(340). Palmitylethanolamide, physiologically present in
      human reproductive tracts, affects the time-course of in-vitro capacitation,
      increasing the rate of this process only in the cells with a lower membrane
      polarity.

PMID- 12802045
TI  - Plasma membrane and vesicular monoamine transporters in normal endometrium and
      early pregnancy decidua.
AB  - The uterus is innervated by adrenergic sympathetic fibres, and the endometrium
      has a capability for endogenous monoamine synthesis. Extracellular monoamine
      levels are regulated primarily through re-uptake by specific membrane-bound
      transporter proteins dopamine transporter (DAT), norepinephrine transporter (NET)
      and serotonin transporter (SERT). Intracellular storage of monoamines involves
      vesicular transporter proteins (VMAT1 and VMAT2). This study explored gene
      expression of the monoamine transporters in normal endometrium throughout the
      menstrual cycle and early decidua. In-situ hybridization histochemistry revealed
      three general classes of expression patterns: (i). epithelial expression of NET
      mRNA; (ii). increasing stromal expression of VMAT2 mRNA in the proliferative
      phase; and (iii). increasing epithelial expression of VMAT2 mRNA during the
      secretory phase. Real time PCR showed low expression levels of NET in all phases
      of the endometrial cycle and a higher expression of VMAT2 mRNA in the mid
      secretory phase. Our results suggest that several monoamine transporters may have
      menstrual cycle phase-specific functions in endometrial biology by maintaining
      adequate levels of monoamines. Re-uptake and regulated release of monoamines may
      also modulate several steps of the reproductive processes such as embryo
      implantation and decidua formation.

PMID- 12802046
TI  - Modulation of placental vascular endothelial growth factor by leptin and hCG.
AB  - Vascular endothelial growth factor (VEGF) has been identified as an endothelium
      specific mitogen and inducer of angiogenesis and endothelial cell survival.
      Leptin and hCG have also been suggested as possible regulators of angiogenesis in
      various models. In-vivo and in-vitro assays revealed that leptin has an
      angiogenic activity and that the vascular endothelium is a target for leptin.
      Thus, we hypothesized that products of cytotrophoblastic cells may play a role in
      placental angiogenesis and we therefore investigated the effects of leptin and
      hCG on cytotrophoblast VEGF secretion. We incubated cytotrophoblastic cells (CTB)
      with recombinant human leptin (rhLept) (0-4 pg/ml) or hCG (0-30000 IU/ml) for 4
      h. rhLept significantly stimulated hCG (P = 0.0045) and decreased VEGF release (P
      = 0.0008) by CTB in a concentration-dependent manner. On the other hand,
      increasing concentrations of hCG (0-30000 IU/ml), induced a significant
      inhibition of leptin secretion (P = 0.0028) and a marked dose-dependent
      stimulation of VEGF(165) secretion (P < 0.0001). We observed an increase of >1000
      fold in basal trophoblastic VEGF secretion with physiological concentrations of
      hCG in vitro. An inhibitory effect of hCG on trophoblastic leptin secretion was
      also observed, suggesting that hCG might exert a possible negative feedback on
      trophoblastic release of leptin. We hypothesize that trophoblastic products such
      as hCG and leptin are probably involved in the control of VEGF secretion at the
      maternal-fetal interface.

PMID- 12802047
TI  - The minisequencing method: an alternative strategy for preimplantation genetic
      diagnosis of single gene disorders.
AB  - We have applied a new method of genetic analysis, called 'minisequencing', to
      preimplantation genetic diagnosis (PGD) of monogenic disorders from single cells.
      This method involves computer-assisted mutation analysis, which allows exact base
      identity determination and computer-assisted visualization of the specific
      mutation(s), and thus facilitates data interpretation and management. Sequencing
      of the entire PCR product is unnecessary, yet the same qualitative
      characteristics of sequence analysis are maintained. The main benefit of the
      minisequencing strategy is the use of a mutation analysis protocol based on a
      common procedure, irrespective of the mutations involved. To evaluate the
      reliability of this method for subsequent application to PGD, we analysed PCR
      products from 887 blastomeres including 55 PGD cases of different genetic
      diseases, such as cystic fibrosis, beta-thalassaemia, sickle cell anaemia,
      haemophilia A, retinoblastoma, and spinal muscular atrophy. Minisequencing was
      found to be a useful technique in PGD analysis, due to its elevated sensitivity,
      automation, and easy data interpretation. The method was also efficient,
      providing interpretable results in 96.5% (856/887) of the blastomeres tested.
      Fifteen clinical pregnancies resulted from these PGD cases; conventional prenatal
      diagnosis confirmed all the PGD results, and 10 healthy babies have already been
      born. Its applicability to PGD could be helpful, particularly in cases in which
      the mutation(s) involved are difficult to assess by restriction analysis or other
      commonly used methods.

PMID- 12802048
TI  - Detailed investigation of factors influencing amplification efficiency and allele
      drop-out in single cell PCR: implications for preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) of single gene disorders relies on PCR
      based tests performed on single cells (polar bodies or blastomeres). Despite the
      use of increasingly robust protocols, allele drop-out (ADO; the failure to
      amplify one of the two alleles in a heterozygous cell) remains a significant
      problem for diagnosis using single cell PCR. In extreme cases ADO can affect >40%
      of amplifications and has already caused several PGD misdiagnoses. We suggest
      that an improved understanding of the origins of ADO will allow development of
      more reliable PCR assays. In this study we carefully varied reaction conditions
      in >3000 single cell amplifications, allowing factors influencing ADO rates to be
      identified. ADO was found to be affected by amplicon size, amount of DNA
      degradation, freezing and thawing, the PCR programme, and the number of cells
      simultaneously amplified. Factors found to have little or no affect on ADO were
      local DNA sequence, denaturing temperature (94 or 96 degrees C) and cell type.
      Consideration of the causal factors identified during this study should permit
      the design of PGD protocols that experience little ADO, thus improving the
      accuracy of PGD for single gene disorders.

PMID- 12802049
TI  - Specific detection of deleted and non-deleted dystrophin exons together with
      gender assignment in preimplantation genetic diagnosis of Duchenne muscular
      dystrophy.
AB  - We have developed a preimplantation genetic diagnosis (PGD) strategy for Duchenne
      muscular dystrophy (DMD) allowing the simultaneous amplification of four exons
      (6, 8, 28 and 32) of the dystrophin gene together with ZFX/ZFY genes for gender
      determination. Preliminary experiments were carried out on 215 single lymphocytes
      from male and female individuals. Amplification rates ranged from 90.2% for exon
      6 to 96.7% for exons 8 and 32. At least four of the five sequences were
      successfully amplified in 95.8% of single cells, and sexing was possible in
      98.5%. This 5-plex assay was found to be robust enough to be used in a PGD
      clinical procedure and was therefore applied to a family whose female partner was
      a heterozygous carrier of a large deletion extending from exon 21 to exon 34 of
      the dystrophin gene. We have thus analysed two exons located in the deleted
      region of the gene, two non-deleted exons used as intrasample controls, and
      ZFX/ZFY genes. Cleavage stage embryo biopsy followed by PCR resulted in transfer
      of three unaffected embryos. The advantage of the present approach is to identify
      and subsequently transfer unaffected male embryos in addition to female embryos,
      and is now applicable to all families displaying a deletion involving at least
      one of these exons.

PMID- 12802050
TI  - Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A.
AB  - Charcot-Marie-Tooth (CMT) disease is the 'common' name for a range of hereditary
      peripheral neuropathies. CMT1 is the most common form and is transmitted in an
      autosomal dominant manner. CMT1A maps to chromosome 17p11.2 and is caused, in the
      majority of cases, by a 1.5 Mb DNA duplication, that includes the peripheral
      myelin protein 22 (PMP) gene. This paper reports on preimplantation genetic
      diagnosis (PGD) for CMT1A in five couples. The CMT1A duplication was detected by
      fluorescent PCR analysis using polymorphic (CA)n markers localized within the
      duplication. Single-cell PCR on blastomeres allowed genetic analysis of embryos
      obtained after ICSI. Only healthy unaffected embryos were transferred to the
      uterus. PCR experiments with single EBV-transformed lymphoblasts or with research
      blastomeres allowed the evaluation of amplification efficiencies, as well as
      contamination and allele drop-out (ADO) rates for each PCR protocol. Three
      simplex PCR protocols (using one primer pair) and two duplex PCR protocols (using
      two primer pairs) were developed for CMT1A. Additionally, a protocol using all
      three primer pairs in triplex was also established. Thirteen clinical ICSI-PGD
      cycles were performed for five couples (12 simplex PCR cycles and one duplex PCR
      cycle), resulting in seven embryo transfers. Three singleton pregnancies ensued
      in two couples and three healthy babies were delivered. This report describes
      different fluorescent PCR-based tests which allow efficient and accurate single
      cell level detection of the CMT1A duplication. On the basis of the presence of
      the healthy allele of the affected parent-to-be (and/or absence of the affected
      one), healthy embryos can be selected for transfer. The assays are suitable for
      PGD for other couples who present with the same CMT1A duplication [depending on
      their informativity for the (CA)n markers available] as described here.

PMID- 12802051
TI  - Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory
      light chain of myosin II.
AB  - Citron kinase is a Rho-effector protein kinase that is related to Rho-associated
      kinases of ROCK/ROK/Rho-kinase family. Both ROCK and citron kinase are suggested
      to play a role in cytokinesis. However, no substrates are known for citron
      kinase. We found that citron kinase phosphorylated regulatory light chain (MLC)
      of myosin II at both Ser-19 and Thr-18 in vitro. Unlike ROCK, however, citron
      kinase did not phosphorylate the myosin binding subunit of myosin phosphatase,
      indicating that it does not inhibit myosin phosphatase. We found that the
      expression of the kinase domain of citron kinase resulted in an increase in MLC
      di-phosphorylation. Furthermore, the kinase domain was able to increase di
      phosphorylation and restore stress fiber assembly even when ROCK was inhibited
      with a specific inhibitor, Y-27632. The expression of full-length citron kinase
      also increased di-phosphorylation during cytokinesis. These observations suggest
      that citron kinase phosphorylates MLC to generate di-phosphorylated MLC in vivo.
      Although both mono- and di-phosphorylated MLC were found in cleavage furrows, di
      phosphorylated MLC showed more constrained localization than did mono
      phosphorylated MLC. Because citron kinase is localized in cleavage furrows,
      citron kinase may be involved in regulating di-phosphorylation of MLC during
      cytokinesis.

PMID- 12802052
TI  - NZO-3 expression causes global changes to actin cytoskeleton in Madin-Darby
      canine kidney cells: linking a tight junction protein to Rho GTPases.
AB  - We previously demonstrated that exogenous expression of a truncated form of the
      tight junction protein ZO-3 affected junctional complex assembly and function.
      Current results indicate that this ZO-3 construct influences actin cytoskeleton
      dynamics more globally. We show that expression of the amino-terminal half of ZO
      3 (NZO-3) in Madin-Darby canine kidney cells results in a decreased number of
      stress fibers and focal adhesions and causes an increased rate of cell migration
      in a wound healing assay. We also demonstrate that RhoA activity is reduced in
      NZO-3-expressing cells. We determined that ZO-3 interacts with p120 catenin and
      AF-6, proteins localized to the junctional complex and implicated in signaling
      pathways important for cytoskeleton regulation and cell motility. We also provide
      evidence that NZO-3 interacts directly with the C terminus of ZO-3, and we
      propose a model where altered interactions between ZO-3 and p120 catenin in NZO-3
      expressing cells affect RhoA GTPase activity. This study reveals a potential link
      between ZO-3 and RhoA-related signaling events.

PMID- 12802053
TI  - A high-order trans-membrane structural linkage is responsible for mitochondrial
      genome positioning and segregation by flagellar basal bodies in trypanosomes.
AB  - In trypanosomes, the large mitochondrial genome within the kinetoplast is
      physically connected to the flagellar basal bodies and is segregated by them
      during cell growth. The structural linkage enabling these phenomena is unknown.
      We have developed novel extraction/fixation protocols to characterize the links
      involved in kinetoplast-flagellum attachment and segregation. We show that three
      specific components comprise a structure that we have termed the tripartite
      attachment complex (TAC). The TAC involves a set of filaments linking the basal
      bodies to a zone of differentiated outer and inner mitochondrial membranes and a
      further set of intramitochondrial filaments linking the inner face of the
      differentiated membrane zone to the kinetoplast. The TAC and flagellum
      kinetoplast DNA connections are sustained throughout the cell cycle and are
      replicated and remodeled during the periodic kinetoplast DNA S phase. This
      understanding of the high-order trans-membrane linkage provides an explanation
      for the spatial position of the trypanosome mitochondrial genome and its
      mechanism of segregation. Moreover, the architecture of the TAC suggests that it
      may also function in providing a structural and vectorial role during replication
      of this catenated mass of mitochondrial DNA. We suggest that this complex may
      represent an extreme form of a more generally occurring
      mitochondrion/cytoskeleton interaction.

PMID- 12802054
TI  - Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that
      attaches GPI-anchors to proteins.
AB  - Many eukaryotic proteins are anchored to the cell surface via
      glycosylphosphatidylinositol (GPI), which is posttranslationally attached to the
      carboxyl-terminus by GPI transamidase. The mammalian GPI transamidase is a
      complex of at least four subunits, GPI8, GAA1, PIG-S, and PIG-T. Here, we report
      Chinese hamster ovary cells representing a new complementation group of GPI
      anchored protein-deficient mutants, class U. The class U cells accumulated mature
      and immature GPI and did not have in vitro GPI transamidase activity. We cloned
      the gene responsible, termed PIG-U, that encoded a 435-amino-acid hydrophobic
      protein. The GPI transamidase complex affinity-purified from cells expressing
      epitope-tagged-GPI8 contained PIG-U and four other known components. Cells
      lacking PIG-U formed complexes of the four other components normally but had no
      ability to cleave the GPI attachment signal peptide. Saccharomyces cerevisiae
      Cdc91p, with 28% amino acid identity to PIG-U, partially restored GPI-anchored
      proteins on the surface of class U cells. PIG-U and Cdc91p have a functionally
      important short region with similarity to a region conserved in long-chain fatty
      acid elongases. Taken together, PIG-U and the yeast orthologue Cdc91p are the
      fifth component of GPI transamidase that may be involved in the recognition of
      either the GPI attachment signal or the lipid portion of GPI.

PMID- 12802055
TI  - Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition
      of human colonic organoids.
AB  - An epithelial-mesenchymal transition (EMT) characterizes the progression of many
      carcinomas and it is linked to the acquisition of an invasive phenotype. Given
      that the tumor microenvironment is an active participant in tumor progression, an
      important issue is whether a reactive stroma can modulate this process. Using a
      novel EMT model of colon carcinoma spheroids, we demonstrate that their
      transforming-growth factor-beta1 (TGF-beta)-induced EMT is accelerated
      dramatically by the presence of activated macrophages, and we identify tumor
      necrosis factor-alpha (TNF-alpha) as the critical factor produced by macrophages
      that accelerates the EMT. A synergy of TNF-alpha and TGF-beta signaling promotes
      a rapid morphological conversion of the highly organized colonic epithelium to
      dispersed cells with a mesenchymal phenotype, and this process is dependent on
      enhanced p38 MAPK activity. Moreover, exposure to TNF-alpha stimulates a rapid
      burst of ERK activation that results in the autocrine production of this cytokine
      by the tumor cells themselves. These results establish a novel role for the
      stroma in influencing EMT in colon carcinoma, and they identify a selective
      advantage to the stromal presence of infiltrating leukocytes in regulating
      malignant tumor progression.

PMID- 12802056
TI  - Basolateral cycling mediated by a lumenal domain targeting determinant.
AB  - All identified basolateral sorting signals of integral membrane proteins are
      cytoplasmically disposed, suggesting that basolateral targeting is mediated
      exclusively by direct interaction with vesicle coat components. Here, we report
      that GPP130, a cis-Golgi protein that undergoes endosome-to-Golgi retrieval using
      the late endosome-bypass pathway in nonpolarized cells, cycles via the
      basolateral membrane in polarized MDCK cells. Significantly, the membrane
      proximal lumenal domain of GPP130, which mediates GPP130 localization and
      trafficking in nonpolarized cells, was both necessary and sufficient for
      basolateral cycling in MDCK cells. The use of lumenal determinants for both
      basolateral cycling and endosome-to-Golgi retrieval suggests that a novel
      receptor-mediated mechanism operates at both the trans-Golgi network and distal
      sites to sort GPP130 along the late-endosome-bypass retrieval pathway in
      polarized cells.

PMID- 12802057
TI  - Controlled damage in thick specimens by multiphoton excitation.
AB  - Controlled damage by light energy has been a valuable tool in studies of cell
      function. Here, we show that the Ti:Sapphire laser in a multiphoton microscope
      can be used to cause localized damage within unlabeled cells or tissues at
      greater depths than previously possible. We show that the damage is due to a
      multiphoton process and made wounds as small as 1 microm in diameter 20 microm
      from the surface. A characteristic fluorescent scar allows monitoring of the
      damage and identifies the wound site in later observations. We were able to
      lesion a single axon within a bundle of nerves, locally interrupt organelle
      transport within one axon, cut dendrites in a zebrafish embryo, ablate a mitotic
      pole in a sea urchin egg, and wound the plasma membrane and nuclear envelope in
      starfish oocytes. The starfish nucleus collapsed approximately 1 h after
      wounding, indicating that loss of compartmentation barrier makes the structure
      unstable; surprisingly, the oocyte still completed meiotic divisions when exposed
      to maturation hormone, indicating that the compartmentalization and translocation
      of cdk1 and its regulators is not required for this process. Multiphoton
      excitation provides a new means for producing controlled damage deep within
      tissues or living organisms.

PMID- 12802058
TI  - Centrin4p, a novel mammalian centrin specifically expressed in ciliated cells.
AB  - Centriole assembly plays an important role in centrosome duplication during the
      cell cycle and is a prerequisite for cilia formation during the differentiation
      of ciliated cells. In spite of numerous investigations, the molecular machinery
      that governs centriole/basal body formation remains enigmatic. Recent reports
      suggest that the ubiquitously expressed mammalian centrins, centrin2p and
      centrin3p, could be involved in the centriole duplication process. To better
      understand the specific functions of these proteins, we performed a systematic
      search for novel mammalian centrins. We isolated a cDNA and the corresponding
      gene coding for a novel murine centrin, centrin4p, which is more closely related
      to centrin2p. Like centrin2p, centrin4p accumulates to centrioles and
      procentrioles when ectopically expressed in HeLa cells. However, centrin4p
      possesses two splice variants that do not localize to centrioles, suggesting a
      posttranscriptional regulation mechanism. We also observed that centrin4p does
      not share the same centriolar targeting properties with centrin2p and 3p,
      indicating that these proteins could recognize different centriolar partners.
      Centrin4 mRNA possesses a restricted expression profile and is only detected in
      brain, kidney, lung, and ovary. In brain, centrin4p is exclusively expressed in
      ependymal and choroidal ciliated cells where it is localized to basal bodies.
      Together, our present data suggest that centrin4p could be more specifically
      involved in basal bodies assembly or in a subsequent step of ciliogenesis.

PMID- 12802060
TI  - Dual prenylation is required for Rab protein localization and function.
AB  - The majority of Rab proteins are posttranslationally modified with two
      geranylgeranyl lipid moieties that enable their stable association with
      membranes. In this study, we present evidence to demonstrate that there is a
      specific lipid requirement for Rab protein localization and function.
      Substitution of different prenyl anchors on Rab GTPases does not lead to correct
      function. In the case of YPT1 and SEC4, two essential Rab genes in Saccharomyces
      cerevisiae, alternative lipid tails cannot support life when present as the sole
      source of YPT1 and SEC4. Furthermore, our data suggest that double geranyl
      geranyl groups are required for Rab proteins to correctly localize to their
      characteristic organelle membrane. We have identified a factor, Yip1p that
      specifically binds the di-geranylgeranylated Rab and does not interact with mono
      prenylated Rab proteins. This is the first demonstration that the double
      prenylation modification of Rab proteins is an important feature in the function
      of this small GTPase family and adds specific prenylation to the already known
      determinants of Rab localization.

PMID- 12802059
TI  - The AP-1 clathrin-adaptor is required for lysosomal enzymes sorting and
      biogenesis of the contractile vacuole complex in Dictyostelium cells.
AB  - Adaptor protein complexes (AP) are major components of the cytoplasmic coat found
      on clathrin-coated vesicles. Here, we report the molecular and functional
      characterization of Dictyostelium clathrin-associated AP-1 complex, which in
      mammalian cells, participates mainly in budding of clathrin-coated vesicles from
      the trans-Golgi network (TGN). The gamma-adaptin AP-1 subunit was cloned and
      shown to belong to a Golgi-localized 300-kDa protein complex. Time-lapse analysis
      of cells expressing gamma-adaptin tagged with the green-fluorescent protein
      demonstrates the dynamics of AP-1-coated structures leaving the Golgi apparatus
      and rarely moving toward the TGN. Targeted disruption of the AP-1 medium chain
      results in viable cells displaying a severe growth defect and a delayed
      developmental cycle compared with parental cells. Lysosomal enzymes are
      constitutively secreted as precursors, suggesting that protein transport between
      the TGN and lysosomes is defective. Although endocytic protein markers are
      correctly localized to endosomal compartments, morphological and ultrastructural
      studies reveal the absence of large endosomal vacuoles and an increased number of
      small vacuoles. In addition, the function of the contractile vacuole complex
      (CV), an osmoregulatory organelle is impaired and some CV components are not
      correctly targeted.

PMID- 12802061
TI  - Ykt6p is a multifunctional yeast R-SNARE that is required for multiple membrane
      transport pathways to the vacuole.
AB  - Intracellular membrane fusion requires that membrane-bound soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins on
      both vesicle and target membranes form a highly specific complex necessary to
      bring the membranes close in space. Ykt6p is a yeast R-SNARE protein that has
      been implicated in retrograde transport to the cis-Golgi compartment. Ykt6p has
      been also been found to fractionate with vacuole membranes and participate in a
      vacuolar SNARE complex in homotypic vacuole fusion. To investigate the role of
      Ykt6p in membrane traffic to the vacuole we generated temperature-sensitive
      mutations in YKT6. One mutation produces an early Golgi block to secretion, and
      overexpression of the SNARE protein Sft1p suppresses the growth and secretion
      defects of this mutation. These results are consistent with Ykt6p and Sft1p
      participating in a SNARE complex associated with retrograde transport to the cis
      Golgi. A second set of mutations in YKT6 specifically affects post-Golgi membrane
      traffic to the vacuole, and the effects of these mutations are not suppressed by
      Sft1p overexpression. Defects are seen in carboxypeptidase Y sorting, alkaline
      phosphatase transport, and aminopeptidase I delivery, and in one mutant,
      overexpression of the SNARE protein Nyv1p suppresses the alkaline phosphatase
      transport defect. By mutationally separating early and late requirements for
      Ykt6p, our findings have revealed that Ykt6p is a R-SNARE protein that functions
      directly in the three biosynthetic pathways to the vacuole.

PMID- 12802062
TI  - Membrane targeting of Rab GTPases is influenced by the prenylation motif.
AB  - Rab GTPases are regulators of membrane traffic. Rabs specifically associate with
      target membranes via the attachment of (usually) two geranylgeranyl groups in a
      reaction involving Rab escort protein and Rab geranylgeranyl transferase. In
      contrast, related GTPases are singly prenylated by CAAX prenyl transferases. We
      report that di-geranylgeranyl modification is important for targeting of Rab5a
      and Rab27a to endosomes and melanosomes, respectively. Transient expression of
      EGFP-Rab5 mutants containing two prenylatable cysteines (CGC, CC, CCQNI, and CCA)
      in HeLa cells did not affect endosomal targeting or function, whereas mono
      cysteine mutants (CSLG, CVLL, or CVIM) were mistargeted to the endoplasmic
      reticulum (ER) and were nonfunctional. Similarly, Rab27aCVLL mutant is also
      mistargeted to the ER and transgenic expression on a Rab27a null background
      (Rab27aash) did not rescue the coat color phenotype, suggesting that Rab27aCVLL
      is not functional in vivo. CAAX prenyl transferase inhibition and temperature
      shift experiments further suggest that Rabs, singly or doubly modified are
      recruited to membranes via a Rab escort protein/Rab geranylgeranyl transferase
      dependent mechanism that is distinct from the insertion of CAAX-containing
      GTPases. Finally, we show that both singly and doubly modified Rabs are extracted
      from membranes by RabGDIalpha and propose that the mistargeting of Rabs to the ER
      results from loss of targeting information.

PMID- 12802063
TI  - Actin dynamics is controlled by a casein kinase II and phosphatase 2C interplay
      on Toxoplasma gondii Toxofilin.
AB  - Actin polymerization in Apicomplexa protozoa is central to parasite motility and
      host cell invasion. Toxofilin has been characterized as a protein that sequesters
      actin monomers and caps actin filaments in Toxoplasma gondii. Herein, we show
      that Toxofilin properties in vivo as in vitro depend on its phosphorylation. We
      identify a novel parasitic type 2C phosphatase that binds the Toxofilin/G-actin
      complex and a casein kinase II-like activity in the cytosol, both of which
      modulate the phosphorylation status of Toxofilin serine53. The interplay of these
      two molecules controls Toxofilin binding of G-actin as well as actin dynamics in
      vivo. Such functional interactions should play a major role in actin
      sequestration, a central feature of actin dynamics in Apicomplexa that underlies
      the spectacular speed and nature of parasite gliding motility.

PMID- 12802064
TI  - Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of
      chemotaxing cells.
AB  - Recent studies have demonstrated that PH domains specific for PI(3,4,5)P3
      accumulate at the leading edge of a number of migrating cells and that PI3Ks and
      PTEN associate with the membrane at the front and back, respectively, of
      chemotaxing Dictyostelium discoideum cells. However, the dependence of
      chemoattractant induced changes in PI(3,4,5)P3 on PI3K and PTEN activities have
      not been defined. We find that bulk PI(3,4,5)P3 levels increase transiently upon
      chemoattractant stimulation, and the changes are greater and more prolonged in
      pten- cells. PI3K activation increases within 5 s of chemoattractant addition and
      then declines to a low level of activity identically in wild-type and pten-
      cells. Reconstitution of the PI3K activation profile can be achieved by mixing
      membranes from stimulated pi3k1-/pi3k2- cells with cytosolic PI3Ks from
      unstimulated cells. These studies show that significant control of chemotaxis
      occurs upstream of the PI3Ks and that regulation of the PI3Ks and PTEN cooperate
      to shape the temporal and spatial localization of PI(3,4,5)P3.

PMID- 12802065
TI  - Direct interaction with nup153 mediates binding of Tpr to the periphery of the
      nuclear pore complex.
AB  - Tpr is a 267-kDa protein forming coiled coil-dominated homodimers that locate at
      the nucleoplasmic side of the nuclear pore complex (NPC). The proteins that
      tether Tpr to this location are unknown. Moreover, the question whether Tpr
      itself might act as a scaffold onto which other NPC components need to be
      assembled has not been answered to date. To assess Tpr's role as an architectural
      element of the NPC, we have studied the sequential disassembly and reassembly of
      NPCs in mitotic cells, paralleled by studies of cells depleted of Tpr as a result
      of posttranscriptional tpr gene silencing by RNA interference (RNAi). NPC
      assembly and recruitment of several nucleoporins, including Nup50, Nup93, Nup96,
      Nup98, Nup107, and Nup153, in anaphase/early telophase is shown to precede NPC
      association of Tpr in late telophase. In accordance, cellular depletion of Tpr by
      RNAi does not forestall binding of these nucleoporins to the NPC. In a search for
      proteins that moor Tpr to the NPC, we have combined the RNAi approach with
      affinity-chromatography and yeast two-hybrid interaction studies, leading to the
      identification of nucleoporin Nup153 as the binding partner for Tpr. The
      specificity of this interaction is demonstrated by its sensitivity to Tpr amino
      acid substitution mutations that abolish Tpr's ability to adhere to the NPC and
      affect the direct binding of Tpr to Nup153. Accordingly, cellular depletion of
      Nup153 by RNAi is shown to result in mislocalization of Tpr to the nuclear
      interior. Nup153 deficiency also causes mislocalization of Nup50 but has no
      direct effect on NPC localization of the other nucleoporins studied in this
      investigation. In summary, these results render Tpr a protein only peripherally
      attached to the NPC that does not act as an essential scaffold for other
      nucleoporins.

PMID- 12802066
TI  - Perlecan up-regulation of FRNK suppresses smooth muscle cell proliferation via
      inhibition of FAK signaling.
AB  - We previously reported that fully assembled basement membranes are nonpermissive
      to smooth muscle cell (SMC) replication and that perlecan (PN), a basement
      membrane heparan sulfate proteoglycan, is a dominant effector of this response.
      We report here that SMC adhesion to basement membranes, and perlecan in
      particular, up-regulate the expression of focal adhesion kinase-related nonkinase
      (FRNK), a SMC-specific endogenous inhibitor of FAK, which subsequently suppresses
      FAK-mediated, ERK1/2-dependent growth signals. Up-regulation of FRNK by perlecan
      is actively and continuously regulated. Relative to the matrix proteins studied,
      the effects are unique to perlecan, because plating of SMCs on several other
      basement membrane proteins is associated with low levels of FRNK and
      corresponding high levels of FAK and ERK1/2 phosphorylation and SMC growth.
      Perlecan supports SMC adhesion, although there is reduced cell spreading compared
      with fibronectin (FN), laminin (LN), or collagen type IV (IV). Despite the
      reduction in cell spreading, we report that perlecan-induced up-regulation of
      FRNK is independent of cell shape changes. Growth inhibition by perlecan was
      rescued by overexpressing a constitutively active FAK construct, but
      overexpressing kinase-inactivated mutant FAK or FRNK attenuated fibronectin
      stimulated growth. These data indicate that perlecan functions as an endogenously
      produced inhibitor of SMC growth at least in part through the active regulation
      of FRNK expression. FRNK, in turn, may control SMC growth by downregulating FAK
      dependent signaling events.

PMID- 12802067
TI  - Constriction and Dnm1p recruitment are distinct processes in mitochondrial
      fission.
AB  - Mitochondria undergo cycles of fusion and fission crucial for organelle
      homeostasis. Fission is regulated partially by recruitment of the large GTPase
      Dnm1p to the outer mitochondrial membrane. Using three-dimensional time-lapse
      fluorescence imaging of Saccharomyces cerevisiae cells, we found that Dnm1p-EGFP
      appears and disappears at "hot spots" along mitochondrial tubes. It forms patches
      that convert rapidly into different shapes regardless of whether mitochondrial
      fission ensues or not. Moreover, the thickness of the mitochondrial matrix
      displays frequent temporal fluctuations apparently unrelated to fission or to
      recruitment of Dnm1p-EGFP. These results suggest that mitochondrial fission
      requires coordination of at least two distinct processes.

PMID- 12802068
TI  - p120 Catenin is required for growth factor-dependent cell motility and scattering
      in epithelial cells.
AB  - Cadherin-mediated cell-cell adhesion is dynamically modulated during epithelial
      mesenchymal transition triggered by activation of receptor tyrosine kinases (RTK)
      in epithelial cells. Several cadherin-binding proteins have been identified that
      control cell-cell adhesion. However, the mechanisms by which intercellular
      adhesion and cell motility are coregulated are still unknown. Here, we delineate
      a hitherto uncharted cooperation between RTKs, RhoA GTPase, and p120 catenin in
      instructing a motile behavior to epithelial cells. We found that expression of an
      N-terminus-deleted p120 catenin in a variety of epithelial cell types, including
      primary keratinocytes, effectively competes for endogenous p120 at cadherin
      binding sites and abrogates EGF-stimulated cell motility as well as HGF-induced
      cell scattering. The deleted mutant also inhibits the PI3K-dependent RhoA
      activation ensuing receptor activation. Conversely, we also show that the ectopic
      expression of full-length p120 in epithelial cells promotes cytoskeletal changes,
      stimulates cell motility, and activates RhoA. Both motogenic response to p120 and
      RhoA activation require coactivation of signaling downstream of RTKs as they are
      suppressed by ablation of the Ras/PI3K pathway. These studies demonstrate that
      p120 catenin is a necessary target of RTKs in regulating cell motility and help
      define a novel pathway leading to RhoA activation, which may contribute to the
      early steps of metastatic invasion.

PMID- 12802069
TI  - Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with
      intermediate filaments is mediated by distinct sequences within their COOH
      terminus.
AB  - The bullous pemphigoid antigen 1 (BP230) and desmoplakin (DP) are members of the
      plakin protein family of cytolinkers. Despite their homology, their COOH termini
      selectively bind distinct intermediate filaments (IFs). We studied sequences
      within their COOH termini required for their interaction with the epidermal
      keratins K5/K14, the simple epithelial keratins K8/K18, and type III IF vimentin
      by yeast three-hybrid, cell transfection, and overlay assays. The results
      indicate that BP230 interacts with K5/K14 but not with K8/K18 or vimentin via a
      region encompassing both the B and C subdomains and the COOH extremity, including
      a COOH-terminal eight-amino-acid stretch. In contrast, the C subdomain with the
      COOH-terminal extremity of DP interacts with K5/K14 and K8/K18, and its linker
      region is able to associate with K8/K18 and vimentin. Furthermore, the potential
      of DP to interact with IF proteins in yeast seems to be regulated by
      phosphorylation of Ser 2849 within its COOH terminus. Strikingly, BP230 and DP
      interacted with cytokeratins only when both type I and type II keratins were
      present. The head and tail domains of K5/K14 keratins were dispensable for their
      interaction with BP230 or DP. On the basis of our findings, we postulate that (1)
      the binding specificity of plakins for various IF proteins depends on their
      linker region between the highly homologous B and C subdomains and their COOH
      extremity and (2) the association of DP and BP230 with both epidermal and simple
      keratins is critically affected by the tertiary structure induced by
      heterodimerization and involves recognition sites located primarily in the rod
      domain of these keratins.

PMID- 12802070
TI  - Centrosomes split in the presence of impaired DNA integrity during mitosis.
AB  - A well-established function of centrosomes is their role in accomplishing a
      successful mitosis that gives rise to a pair of identical daughter cells. We
      recently showed that DNA replication defects and DNA damage in Drosophila embryos
      trigger centrosomal changes, but it remained unclear whether comparable
      centrosomal responses can be provoked in somatic mammalian cells. To investigate
      the centrosomal organization in the presence of impaired DNA integrity, live and
      ultrastructural analysis was performed on gamma-tubulin-GFP and EGFP-alpha
      tubulin-expressing Chinese hamster ovary cells. We have shown that during mitosis
      in the presence of incompletely replicated or damaged DNA, centrosomes split into
      fractions containing only one centriole. This results in the formation of
      multipolar spindles with extra centrosome-like structures. Despite the extra
      centrosomes and the multipolarity of the spindles, cells do exit from mitosis,
      resulting in severe division errors. Our data provide evidence of a novel
      mechanism showing how numerous centrosomes and spindle defects can arise and how
      this can lead to the formation of aneuploid cells.

PMID- 12802071
TI  - Cyclin D1 governs adhesion and motility of macrophages.
AB  - The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that
      phosphorylates and inactivates the retinoblastoma protein, thereby promoting cell
      cycle progression. Cyclin D1 is overexpressed in hematopoetic and epithelial
      malignancies correlating with poor prognosis and metastasis in several cancer
      types. Because tumor-associated macrophages have been shown to enhance malignant
      progression and metastasis, and cyclin D1-deficient mice are resistant to
      oncogene-induced malignancies, we investigated the function of cyclin D1-/- bone
      marrow-derived macrophages. Cyclin D1 deficiency increased focal complex
      formation at the site of substratum contact, and enhanced macrophage adhesion,
      yielding a flattened, circular morphology with reduced membrane ruffles.
      Migration in response to wounding, cytokine-mediated chemotaxis, and
      transendothelial cell migration of cyclin D1-/- bone marrow-derived macrophages
      were all substantially reduced. Thus, apart from proliferative and possible
      motility defects in the tumor cells themselves, the reduced motility and
      invasiveness of cyclin D1-/- tumor-associated macrophages may contribute to the
      tumor resistance of these mice.

PMID- 12802072
TI  - Dynamin regulates focal exocytosis in phagocytosing macrophages.
AB  - Phagocytosis in macrophages is thought to involve insertion of cytoplasmic
      vesicles at sites of membrane expansion before particle ingestion ("focal"
      exocytosis). Capacitance (Cm) measurements of cell surface area were biphasic,
      with an initial rise indicative of exocytosis followed by a fall upon
      phagocytosis. Unlike other types of regulated exocytosis, the Cm rise was
      insensitive to intracellular Ca2+, but was inhibited by guanosine 5'-O-(2
      thio)diphosphate. Particle uptake, but not Cm rise, was affected by
      phosphatidylinositol 3-kinase inhibitors. Inhibition of actin polymerization
      eliminated the Cm rise, suggesting possible coordination between actin
      polymerization and focal exocytosis. Introduction of anti-pan-dynamin IgG blocked
      Cm changes, suggesting that dynamin controls focal exocytosis and thereby
      phagocytosis. Similarly, recombinant glutathione S-transferase*amphiphysin-SH3
      domain, but not a mutated form that cannot bind to dynamin, inhibited both focal
      exocytosis and phagocytosis. Immunochemical analysis of endogenous dynamin
      distribution in macrophages revealed a substantial particulate pool, some of
      which localized to a presumptive endosomal compartment. Expression of enhanced
      green fluorescent protein*dynamin-2 showed a motile dynamin pool, a fraction of
      which migrated toward and within the phagosomal cup. These results suggest that
      dynamin is involved in the production and/or movement of vesicles from an
      intracellular organelle to the cell surface to support membrane expansion around
      the engulfed particle.

PMID- 12802073
TI  - Endocytosis of a glycosylphosphatidylinositol-anchored protein via clathrin
      coated vesicles, sorting by default in endosomes, and exocytosis via RAB11
      positive carriers.
AB  - Recently, proteins linked to glycosylphosphatidylinositol (GPI) residues have
      received considerable attention both for their association with lipid
      microdomains and for their specific transport between cellular membranes. Basic
      features of trafficking of GPI-anchored proteins or glycolipids may be explored
      in flagellated protozoan parasites, which offer the advantage that their surface
      is dominated by these components. In Trypanosoma brucei, the GPI-anchored variant
      surface glycoprotein (VSG) is efficiently sorted at multiple intracellular
      levels, leading to a 50-fold higher membrane concentration at the cell surface
      compared with the endoplasmic reticulum. We have studied the membrane and VSG
      flow at an invagination of the plasma membrane, the flagellar pocket, the sole
      region for endo- and exocytosis in this organism. VSG enters trypanosomes in
      large clathrin-coated vesicles (135 nm in diameter), which deliver their cargo to
      endosomes. In the lumen of cisternal endosomes, VSG is concentrated by default,
      because a distinct class of small clathrin-coated vesicles (50-60 nm in diameter)
      budding from the cisternae is depleted in VSG. TbRAB11-positive cisternal
      endosomes, containing VSG, fragment by an unknown process giving rise to
      intensely TbRAB11- as well as VSG-positive, disk-like carriers (154 nm in
      diameter, 34 nm in thickness), which are shown to fuse with the flagellar pocket
      membrane, thereby recycling VSG back to the cell surface.

PMID- 12802074
TI  - A novel dynein light intermediate chain colocalizes with the retrograde motor for
      intraflagellar transport at sites of axoneme assembly in chlamydomonas and
      Mammalian cells.
AB  - The assembly of cilia and flagella depends on bidirectional intraflagellar
      transport (IFT). Anterograde IFT is driven by kinesin II, whereas retrograde IFT
      requires cytoplasmic dynein 1b (cDHC1b). Little is known about how cDHC1b
      interacts with its cargoes or how it is regulated. Recent work identified a novel
      dynein light intermediate chain (D2LIC) that colocalized with the mammalian
      cDHC1b homolog DHC2 in the centrosomal region of cultured cells. To see whether
      the LIC might play a role in IFT, we characterized the gene encoding the
      Chlamydomonas homolog of D2LIC and found its expression is up-regulated in
      response to deflagellation. We show that the LIC subunit copurifies with cDHC1b
      during flagellar isolation, dynein extraction, sucrose density centrifugation,
      and immunoprecipitation. Immunocytochemistry reveals that the LIC colocalizes
      with cDHC1b in the basal body region and along the length of flagella in wild
      type cells. Localization of the complex is altered in a collection of retrograde
      IFT and length control mutants, which suggests that the affected gene products
      directly or indirectly regulate cDHC1b activity. The mammalian DHC2 and D2LIC
      also colocalize in the apical cytoplasm and axonemes of ciliated epithelia in the
      lung, brain, and efferent duct. These studies, together with the identification
      of an LIC mutation, xbx-1(ok279), which disrupts retrograde IFT in Caenorhabditis
      elegans, indicate that the novel LIC is a component of the cDHC1b/DHC2 retrograde
      IFT motor in a variety of organisms.

PMID- 12802075
TI  - XBX-1 encodes a dynein light intermediate chain required for retrograde
      intraflagellar transport and cilia assembly in Caenorhabditis elegans.
AB  - Intraflagellar transport (IFT) is a process required for flagella and cilia
      assembly that describes the dynein and kinesin mediated movement of particles
      along axonemes that consists of an A and a B complex, defects in which disrupt
      retrograde and anterograde transport, respectively. Herein, we describe a novel
      Caenorhabditis elegans gene, xbx-1, that is required for retrograde IFT and
      shares homology with a mammalian dynein light intermediate chain (D2LIC). xbx-1
      expression in ciliated sensory neurons is regulated by the transcription factor
      DAF-19, as demonstrated previously for genes encoding IFT complex B proteins. XBX
      1 localizes to the base of the cilia and undergoes anterograde and retrograde
      movement along the axoneme. Disruption of xbx-1 results in cilia defects and
      causes behavioral abnormalities observed in other cilia mutants. Analysis of
      cilia in xbx-1 mutants reveals that they are shortened and have a bulb like
      structure in which IFT proteins accumulate. The role of XBX-1 in IFT was further
      confirmed by analyzing the effect that other IFT mutations have on XBX-1
      localization and movement. In contrast to other IFT proteins, retrograde XBX-1
      movement was detected in complex A mutants. Our results suggest that the DLIC
      protein XBX-1 functions together with the CHE-3 dynein in retrograde IFT,
      downstream of the complex A proteins.

PMID- 12802076
TI  - p38 Mitogen-activated protein kinase mediates cell death and p21-activated kinase
      mediates cell survival during chemotherapeutic drug-induced mitotic arrest.
AB  - Activation of the mitotic checkpoint by chemotherapeutic drugs such as taxol
      causes mammalian cells to arrest in mitosis and then undergo apoptosis. However,
      the biochemical basis of chemotherapeutic drug-induced cell death is unclear.
      Herein, we provide new evidence that both cell survival and cell death-signaling
      pathways are concomitantly activated during mitotic arrest by microtubule
      interfering drugs. Treatment of HeLa cells with chemotherapeutic drugs activated
      both p38 mitogen-activated protein kinase (MAPK) and p21-activated kinase (PAK).
      p38 MAPK was necessary for chemotherapeutic drug-induced cell death because the
      p38 MAPK inhibitors SB203580 or SB202190 suppressed cell death. Dominant-active
      MKK6, a direct activator of p38 MAPK, also induced cell death by stimulating
      translocation of Bax from the cytosol to the mitochondria in a p38 MAPK-dependent
      manner. Dominant active PAK suppressed this MKK6-induced cell death. PAK seems to
      mediate cell survival by phosphorylating Bad, and inhibition of PAK in
      mitotically arrested cells reduced Bad phosphorylation and increased apoptosis.
      Our results suggest that therapeutic strategies that suppress PAK-mediated
      survival signals may improve the efficacy of current cancer chemotherapies by
      enhancing p38 MAPK-mediated cell death.

PMID- 12802077
TI  - Opposing roles of integrin alpha6Abeta1 and dystroglycan in laminin-mediated
      extracellular signal-regulated kinase activation.
AB  - Laminin-integrin interactions can in some settings activate the extracellular
      signal-regulated kinases (ERKs) but the control mechanisms are poorly understood.
      Herein, we studied ERK activation in response to two laminins isoforms (-1 and 
      10/11) in two epithelial cell lines. Both cell lines expressed beta1-containing
      integrins and dystroglycan but lacked integrin alpha6beta4. Antibody perturbation
      assays showed that both cell lines bound to laminin-10/11 via the alpha3beta1and
      alpha6beta1 integrins. Although laminin-10/11 was a stronger adhesion complex
      than laminin-1 for both cell lines, both laminins activated ERK in only one of
      the two cell lines. The ERK activation was mediated by integrin alpha6beta1 and
      not by alpha3beta1 or dystroglycan. Instead, we found that dystroglycan-binding
      domains of both laminin-1 and -10/11 suppressed integrin alpha6beta1-mediated ERK
      activation. Moreover, the responding cell line expressed the two integrin alpha6
      splice variants, alpha6A and alpha6B, whereas the nonresponding cell line
      expressed only alpha6B. Furthermore, ERK activation was seen in cells transfected
      with the integrin alpha6A subunit, but not in alpha6B-transfected cells. We
      conclude that laminin-1 and -10/11 share the ability to induce ERK activation,
      that this is regulated by integrin alpha6Abeta1, and suggest a novel role for
      dystroglycan-binding laminin domains as suppressors of this activation.

PMID- 12802078
TI  - Importin beta-depending nuclear import pathways: role of the adapter proteins in
      the docking and releasing steps.
AB  - Nuclear imports of uridine-rich small nuclear ribonucleoprotein (U1 snRNP) and
      proteins with classical nuclear localization signal (cNLS-protein) are mediated
      by importin beta. However, due to the presence of different import signals, the
      adapter protein of the imported molecules and importin beta is different for each
      pathway. Although the adapter for cNLS-protein is importin alpha, the adapter for
      U1 snRNP is snurportin1 (SPN1). Herein, we show that the use of distinct adapters
      by importin beta results in differences at the docking and releasing step for
      these two import pathways. Nuclear pore complex (NPC) docking of U1 snRNP but not
      of cNLS-protein was inhibited by an anti-CAN/Nup214 antibody. Thus, the initial
      NPC-binding site is different for each pathway. Pull-down assays between
      immobilized SPN1 and two truncated forms of importin beta documented that SPN1
      and importin alpha have different binding sites on importin beta. Importin beta
      fragment 1-618, which binds to SPN1 but not to importin alpha, was able to
      support the nuclear import of U1 snRNPs. After the translocation through the NPC,
      both import complexes associated with the nuclear side of the NPC. However, we
      found that the nature of the importin beta-binding domain of the adapters
      influences the release of the cargo into the nucleoplasm.

PMID- 12802079
TI  - COPI recruitment is modulated by a Rab1b-dependent mechanism.
AB  - The small GTPase Rab1b is essential for endoplasmic reticulum (ER) to Golgi
      transport, but its exact function remains unclear. We have examined the effects
      of wild-type and three mutant forms of Rab1b in vivo. We show that the inactive
      form of Rab1b (the N121I mutant with impaired guanine nucleotide binding) blocks
      forward transport of cargo and induces Golgi disruption. The phenotype is
      analogous to that induced by brefeldin A (BFA): it causes resident Golgi proteins
      to relocate to the ER and induces redistribution of ER-Golgi intermediate
      compartment proteins to punctate structures. The COPII exit machinery seems to be
      functional in cells expressing the N121I mutant, but COPI is compromised, as
      shown by the release of beta-COP into the cytosol. Our results suggest that Rab1b
      function influences COPI recruitment. In support of this, we show that the
      disruptive effects of N121I can be reversed by expressing known mediators of COPI
      recruitment, the GTPase ARF1 and its guanine nucleotide exchange factor GBF1.
      Further evidence is provided by the finding that cells expressing the active form
      of Rab1b (the Q67L mutant with impaired GTPase activity) are resistant to BFA.
      Our data suggest a novel role for Rab1b in ARF1- and GBF1-mediated COPI
      recruitment pathway.

PMID- 12802080
TI  - Septins, under Cla4p regulation, and the chitin ring are required for neck
      integrity in budding yeast.
AB  - CLA4, encoding a protein kinase of the PAK type, and CDC11, encoding a septin,
      were isolated in a screen for synthetic lethality with CHS3, which encodes the
      chitin synthase III catalytic moiety. Although Ste20p shares some essential
      function with Cla4p, it did not show synthetic lethality with Chs3p. cla4 and
      cdc11 mutants exhibited similar morphological and septin localization defects,
      including aberrant and ectopic septa. Myo1p, which requires septins for
      localization, formed abnormally wide rings in cla4 mutants. In cultures started
      with unbudded cells, an inhibitor of Chs3p activity, nikkomycin Z, aggravated the
      abnormalities of cla4 and cdc11 mutants and gave rise to enlarged necks at the
      mother-bud junction, leading to cell death. It is concluded that Cla4p is
      required for the correct localization and/or assembly of the septin ring and that
      both the septin ring and the Chs3p-requiring chitin ring at the mother-bud neck
      cooperate in maintaining the neck constricted throughout the cell cycle, a vital
      function in budding yeast.

PMID- 12802081
TI  - Continuous equilibration of phosphatidylcholine and its precursors between
      endoplasmic reticulum and mitochondria in yeast.
AB  - In Saccharomyces cerevisiae phosphatidylcholine (PC) is synthesized in the ER and
      transported to mitochondria via an unknown mechanism. The transport of PC
      synthesized by the triple methylation of phosphatidylethanolamine was
      investigated by pulsing yeast spheroplasts with l-[methyl-3H]methionine, followed
      by a chase with unlabeled methionine and subcellular fractionation. During the
      pulse, increasing amounts of PC and its mono- and dimethylated precursors (PMME
      and PDME, respectively) appear in similar proportions in both microsomes and
      mitochondria, with the extent of incorporation in microsomes being twice that in
      mitochondria. During the chase, the [3H]-methyl label from the precursors
      accumulates into PC with similar kinetics in both organelles. The results
      demonstrate that transport of methylated phospholipids from ER to mitochondria is
      1) coupled to synthesis, 2) not selective for PC, 3) at least as fast as the
      fastest step in the methylation of PE, and 4) bidirectional for PMME and PDME.
      The interorganellar equilibration of methylated phospholipids was reconstituted
      in vitro and did not depend on ongoing methylation, cytosolic factors, ATP, and
      energization of the mitochondria, although energization could accelerate the
      reaction. The exchange of methylated phospholipids was reduced after pretreating
      both microsomes and mitochondria with trypsin, indicating the involvement of
      membrane proteins from both organelles.

PMID- 12802082
TI  - MyoD distal regulatory region contains an SRF binding CArG element required for
      MyoD expression in skeletal myoblasts and during muscle regeneration.
AB  - We show here that the distal regulatory region (DRR) of the mouse and human MyoD
      gene contains a conserved SRF binding CArG-like element. In electrophoretic
      mobility shift assays with myoblast nuclear extracts, this CArG sequence,
      although slightly divergent, bound two complexes containing, respectively, the
      transcription factor YY1 and SRF associated with the acetyltransferase CBP and
      members of C/EBP family. A single nucleotide mutation in the MyoD-CArG element
      suppressed binding of both SRF and YY1 complexes and abolished DRR enhancer
      activity in stably transfected myoblasts. This MyoD-CArG sequence is active in
      modulating endogeneous MyoD gene expression because microinjection of
      oligonucleotides corresponding to the MyoD-CArG sequence specifically and rapidly
      suppressed MyoD expression in myoblasts. In vivo, the expression of a transgenic
      construct comprising a minimal MyoD promoter fused to the DRR and beta
      galactosidase was induced with the same kinetics as MyoD during mouse muscle
      regeneration. In contrast induction of this reporter was no longer seen in
      regenerating muscle from transgenic mice carrying a mutated DRR-CArG. These
      results show that an SRF binding CArG element present in MyoD gene DRR is
      involved in the control of MyoD gene expression in skeletal myoblasts and in
      mature muscle satellite cell activation during muscle regeneration.

PMID- 12802083
TI  - Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent
      hyphal-like growth.
AB  - Morphogenesis in the fungal pathogen Candida albicans is an important virulence
      determining factor, as a dimorphic switch between yeast and hyphal growth forms
      can increase pathogenesis. We identified CaCDC5, a cell cycle regulatory polo
      like kinase (PLK) in C. albicans and demonstrate that shutting off its expression
      induced cell cycle defects and dramatic changes in morphology. Cells lacking
      CaCdc5p were blocked early in nuclear division with very short spindles and
      unseparated chromatin. GFP-tagged CaCdc5p localized to unseparated spindle pole
      bodies, the spindle, and chromatin, consistent with a role in spindle elongation
      at an earlier point in the cell cycle than that described for the homologue Cdc5p
      in yeast. Strikingly, the cell cycle defects were accompanied by the formation of
      hyphal-like filaments under yeast growth conditions. Filament growth was
      determinate, as the filaments started to die after 24 h. The filaments resembled
      serum-induced hyphae with respect to morphology, organization of cytoplasmic
      microtubules, localization of nuclei, and expression of hyphal-specific
      components. Filament formation required CaCDC35, but not EFG1 or CPH1. Similar
      defects in spindle elongation and a corresponding induction of filaments occurred
      when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to
      act as a direct repressor of hyphal growth, the data suggest that a target of
      CaCdc5p function is associated with hyphal-like development. Thus, an internal,
      cell cycle-related cue can activate hyphal regulatory networks in Candida.

PMID- 12802084
TI  - Ezrin regulates E-cadherin-dependent adherens junction assembly through Rac1
      activation.
AB  - Ezrin, a membrane cytoskeleton linker, is involved in cellular functions,
      including epithelial cell morphogenesis and adhesion. A mutant form of ezrin,
      ezrin T567D, maintains the protein in an open conformation, which when expressed
      in Madin-Darby canine kidney cells causes extensive formation of lamellipodia and
      altered cell-cell contacts at low cell density. Furthermore, these cells do not
      form tubules when grown in a collagen type I matrix. While measuring the activity
      of Rho family GTPases, we found that Rac1, but not RhoA or Cdc 42, is activated
      in ezrin T567D-expressing cells, compared with cells expressing wild-type ezrin.
      Together with Rac1 activation, we observed an accumulation of E-cadherin in
      intracellular compartments and a concomitant decrease in the level of E-cadherin
      present at the plasma membrane. This effect could be reversed with a dominant
      negative form of Rac1, N17Rac1. We show that after a calcium switch, the delivery
      of E-cadherin from an internalized pool to the plasma membrane is greatly delayed
      in ezrin T567D-producing cells. In confluent cells, ezrin T567D production
      decreases the rate of E-cadherin internalization. Our results identify a new role
      for ezrin in cell adhesion through the activation of the GTPase Rac1 and the
      trafficking of E-cadherin to the plasma membrane.

PMID- 12802085
TI  - Spindle formation in Aspergillus is coupled to tubulin movement into the nucleus.
AB  - In many important organisms, including many algae and most fungi, the nuclear
      envelope does not disassemble during mitosis. This fact raises the possibility
      that mitotic onset and/or exit might be regulated, in part, by movement of
      important mitotic proteins into and out of the nucleoplasm. We have used two
      methods to determine whether tubulin levels in the nucleoplasm are regulated in
      the fungus Aspergillus nidulans. First, we have used benomyl to disassemble
      microtubules and create a pool of free tubulin that can be readily observed by
      immunofluorescence. We find that tubulin is substantially excluded from
      interphase nuclei, but is present in mitotic nuclei. Second, we have observed a
      green fluorescent protein/alpha-tubulin fusion in living cells by time-lapse
      spinning-disk confocal microscopy. We find that tubulin is excluded from
      interphase nuclei, enters the nucleus seconds before the mitotic spindle begins
      to form, and is removed from the nucleoplasm during the M-to-G1 transition. Our
      data indicate that regulation of intranuclear tubulin levels plays an important,
      perhaps essential, role in the control of mitotic spindle formation in A.
      nidulans. They suggest that regulation of protein movement into the nucleoplasm
      may be important for regulating mitotic onset in organisms with intranuclear
      mitosis.

PMID- 12802086
TI  - Timing relationships between prosodic and segmental control in Osaka Japanese
      word accent.
AB  - This paper examines onset times of prosodic and segmental transitions with
      corresponding sternohyoid muscle activity in the speech of Osaka Japanese. The
      synchronization between prosodic and segmental control occurs in words combining
      a close vowel followed, directly or indirectly, by an open vowel with High-Low
      accent, including words with devoiced accented vowels. Both segmental and
      prosodic control mechanisms are associated with the activity of the sternohyoid
      muscle. We discuss how the observed segmental-prosodic timing relation can be
      interpreted in terms of muscle contraction control.

PMID- 12802087
TI  - Does babbling sound native? Listener responses to vocalizations produced by
      Swedish and American 12- and 18-month-olds.
AB  - Previous studies of infants' babbling have reported contradictory results as to
      the extent and timing of discernible phonetic influences of the ambient language.
      In the present experiment, five experienced phoneticians were asked to listen for
      ambient language effects on vocalizations produced by American and Swedish 12-
      and 18-month-olds (with 8 children in each language and age group), and to
      motivate their decisions in terms of word or phonetic cue perception. Group
      results indicated that listeners did not perceive effects of ambient language on
      pure babbles for either of the two age groups, whereas a clear effect appeared in
      both age groups given a more liberal definition of babbling. This is taken to
      suggest that results of ambient language listening tests may depend crucially on
      judgments of vocalizations' word status. As compared to the group trends,
      listener responses to individual children's vocalizations did not indicate that a
      majority of either 12- or 18-monthers were sufficiently native-sounding to be
      reliably identified on the basis of ambient language. A closer analysis of
      listeners' use of phonetic cues indicated that one single phonetic property, the
      grave tonal word accent, was discerned by most listeners in vocalizations
      produced by the Swedish 18-monthers; this property was also discerned by one
      listener in vocalizations produced by Swedish 12-monthers. This result is
      consistent with the generally held belief in the primacy of tonal features in
      phonetic acquisition, and with experimental evidence indicating that Swedish
      mothers tend to enhance word accent contours in baby talk. In the final section
      of the paper, the results are discussed with a view to reconcile competing
      theories of babbling development, notably the 'babbling drift' and the
      'independence' hypotheses.

PMID- 12802088
TI  - Corpora analyses of frequency of schwa deletion in conversational American
      English.
AB  - This study utilized two conversational speech databases to generate statistics
      about the frequency of occurrence of schwa deletion. Overall, the results showed
      a low frequency of schwa deletion in conversational American English. We
      investigated a number of factors that could have a potential effect on the
      propensity to delete schwa. The most pervasive factor was stress environment (pre
      stress vs. post-stress), which showed a greater frequency of schwa deletion in
      the post-stress environment. The results are discussed with reference to
      processing spoken words and the role for corpus statistics in constraining models
      of word recognition.

PMID- 12802089
TI  - Experiences of a short vocal training course for call-centre customer service
      advisors.
AB  - It is commonly known that occupational voice users suffer from voice symptoms to
      varying extents. The purpose of this study was to find out the effects of a short
      (2-day) vocal training course on professional speakers' voice. The subjects were
      38 female and 10 male customer advisors, who mainly use the telephone during
      their working hours at a call centre. The findings showed that although the
      subjects did not suffer from severe voice problems, they reported that the short
      vocal training course had an effect of some of the vocal symptoms they had
      experienced. More than 50% of the females and males reported a decrease in the
      feeling of mucus and the consequent need to clear the throat, and diminished
      worsening of their voice. Over 60% thought that voice training had improved their
      vocal habits and none reported a negative influence of the course on their voice.
      Females also reported a reduction of vocal fatigue. The subjects were further
      asked to respond to 23 statements on how they experienced the voice training in
      general. The statements 'I learned things that I didn't know about the use of
      voice in general' and 'I got useful and important knowledge concerning my work'
      were highly assessed by both females and males. The results suggest that even a
      short vocal training course might affect positively the self-reported well-being
      of persons working in a vocally loading occupation. However, to find out the long
      term effects of a short training course, a follow-up study would need to be
      carried out.

PMID- 12802090
TI  - Comparability of perceptual analysis of speech characteristics in Australian and
      Swedish speakers with multiple sclerosis.
AB  - The aims of the present study were to compare the perceptual assessments of
      deviant speech signs (dysarthria) exhibited by Australian and Swedish speakers
      with multiple sclerosis (MS) and to explore whether judgements of dysarthria
      differed depending on whether the speakers and the judges spoke the same or
      different languages. Ten Australian and 10 Swedish individuals with MS (matched
      as closely as possible for age, gender, progression type and severity of
      dysarthria) were assessed by 2 Australian and 2 Swedish clinically experienced
      judges using a protocol including 33 speech parameters. Results show that the
      following perceptual dimensions were identified by both pairs of judges in both
      groups of speakers to a just noticeable or moderate degree: imprecise consonants,
      inappropriate pitch level, reduced general rate, and glottal fry. The reliability
      (Spearman rank-order correlation) of the consensus ratings from the Australian
      and the Swedish judges was high, with a mean rho of 85.7 for the Australian
      speakers and mean rho of 84.3 for the Swedish speakers. The most difficult
      perceptual parameters to assess (i.e. to agree on) included harshness, level of
      pitch and loudness, precision of consonants and general stress pattern. The study
      indicated that perceptual assessments of speech characteristics in individuals
      with MS are informative and can be achieved with high inter-judge reliability
      irrespective of the judge's knowledge of the speaker's language.

PMID- 12802091
TI  - Hypothesis of whiplike motion as a possible traumatizing mechanism in vocal fold
      vibration.
AB  - The mucosal waves on the vibrating vocal folds may move in anterior-posterior,
      mediolateral and in caudal-cranial direction. This article discusses the possible
      significance of the vertical movement from the point of view of mechanical stress
      in phonation and the formation of vocal fold traumas. It is hypothesized that in
      certain conditions the vocal folds may behave in cranial direction like a quasi
      free end of a long lash producing very rapid vibratory waves (e.g. the waves in a
      whiplash). This could be detrimental to the tissue structure. The role of
      phonation type in enhancing/diminishing this effect will also be discussed.

PMID- 12802092
TI  - Effects of two types of tongue strengthening exercises in young normals.
AB  - This pilot study examines the effects of two types of tongue strengthening
      exercises on tongue function measures of strength and endurance in a group of 31
      healthy young subjects. Subjects underwent baseline and 1 month post-baseline
      assessments of tongue function and were randomized to one of three groups,
      including: (1) no exercise; (2) exercise group receiving standard tongue strength
      exercises using a tongue depressor, and (3) exercise group receiving tongue
      strengthening exercises using the Iowa Oral Performance Instrument. Results
      revealed a significantly greater change in maximum tongue strength in the group
      that received any treatment compared with the group receiving no treatment (p =
      0.04). Results provide support for the theory that tongue strengthening exercises
      improve tongue strength in healthy young subjects.

PMID- 12802093
TI  - Identification of differentially expressed genes associated with colorectal
      cancer liver metastasis.
AB  - The molecular mechanisms underlying successful metastasis of primary colorectal
      tumour to the liver remain unknown. We have used suppression subtractive
      hybridisation (SSH) and reverse Northern dot blot analysis to profile the mRNA
      expression patterns of a primary colorectal cancer and its liver metastasis.
      After SSH and reverse Northern dot blot analysis, differential expression was
      confirmed in 17 clones from the forward, and 13 clones from the reverse
      subtracted cDNA library. Four clones showed no significant sequence identities
      with any known sequences in the GenBank data base and likely to represent novel
      genes whose up- or down-regulation is associated with colorectal liver
      metastasis. Interestingly, one of the 13 down-regulated clones displayed 99%
      sequence identity with the BRCA1 tumour suppressor gene. Since promoter
      methylation is a direct cause of transcription silencing of the BRCA1 gene in
      approximately 10-20% of human breast cancer we further investigated its promoter
      methylation status in ten primary colorectal tumour samples, but revealed no
      evidence of promoter methylation.

PMID- 12802094
TI  - Determination of regional bone blood flow by means of fluorescent microspheres
      using an automated sample-processing procedure.
AB  - The determination of regional blood flow utilizing fluorescent microspheres (FMs)
      is an established method for numerous organs. Recent progress, in particular the
      automation of sample processing, has further improved this method. However, the
      FM method (reference sample technique), which allows repetitive measurement of
      regional organ blood flow, has so far not been used for the determination of
      blood flow in bone. The aim of the present study was to establish FM for the
      quantification of regional bone blood flow (RBBF). Female, anesthetized New
      Zealand rabbits (n = 6) received left ventricular injections of different amounts
      of FM at six subsequent time points. In order to examine the precision of RBBF
      determination, two different FM species were injected simultaneously at the sixth
      injection. At the end of the experiments the femoral and tibial condyles of each
      hind limb were removed and the fluorescence intensity in the tissue samples was
      measured by an automated procedure. In an in vitro study we have shown that acid
      digestion of the crystalline matrix has no effect on the fluorescence
      characteristics of FM. The determination of the number of spheres per tissue
      sample revealed that depending on the tissue sample size up to 3 x 10(6)
      spheres/injection were necessary to obtain about 400 microspheres in the
      individual bone samples. RBBF values of the tibial and femoral condyles did not
      differ at various injection intervals. The tibial blood flow values varied
      between 6.6 +/- 1.1 and 8.5 +/- 1.4 ml/min/100 g and were significantly higher
      than those of the femur (4.3 +/- 1.1 to 6.0 +/- 1.8 ml/min/100 g). The bone blood
      flow values obtained by simultaneous injection of two FM species correlated
      significantly (r = 0.96, slope = 1.06, intercept = 0.05), the mean difference was
      0.39 +/- 1.11 ml/min/100 g. Our data demonstrate that the measurement of RBBF by
      means of FM allows a valid determination of RBBF.

PMID- 12802095
TI  - Evaluation of a preclinical model of bone metastasis for the study of adoptive
      immunotherapy.
AB  - The development of new therapeutic strategies for the treatment of bone
      metastases strongly depends on the availability of valid animal models. In this
      paper, we evaluate a preclinical model of bone metastases using a technique of
      tumor cell injection into the left heart ventricle of mice to study the efficacy
      of adoptive immunotherapy. Using flow cytometric analysis and histopathological
      and radiological examination, we investigated whether this experimental model of
      bony metastases using two murine cell lines of melanoma and breast cancer would
      be suitable for the study of adoptive immunotherapy for these diseases. We
      further report that anti-CD3-activated and IL-2-expanded tumor vaccine draining
      lymph node cells cause regression of tumor metastases, including bone metastases,
      following adoptive transfer to mice bearing 3-day metastases from the D5 melanoma
      cell line. These promising early results lead us to conclude the following: (1).
      this model of experimental bone metastases is suitable for the study of
      immunotherapy, and (2). further studies are warranted to extend these promising
      early findings of the therapeutic effects of adoptive immunotherapy in this
      animal model.

PMID- 12802096
TI  - Benefits of intraluminal injection of glutamine for intestinal mucosa during
      ischemia-reperfusion.
AB  - BACKGROUND: We investigated the effect of intraluminal glutamine on the
      intestinal mucosa in the presence of ischemia-reperfusion injury (IRI). METHODS:
      Six blind sacs were created in the small bowel (3 at the jejunum and 3 at the
      ileum) in 10 Wistar rats. The lateral sacs of both bowel regions were submitted
      to IRI (30/30 min), while the medial sacs were left free to receive blood supply.
      In the lateral sacs, a solution containing either saline plus 4% glutamine or
      pure saline was injected at the bowel lumen. No fluid was injected in the medial
      sacs. RESULTS: Both at the jejunum and at the ileum, the score of the mucosal
      injury was higher in saline-injected sacs than in either glutamine-injected or
      control sacs. There was a significantly greater number of neutrophils in the sacs
      treated with saline than in the other two groups of sacs. CONCLUSION: Glutamine
      protects the mucosa and diminishes the accumulation of neutrophils at the lamina
      propria of the small bowel in IRI.

PMID- 12802098
TI  - Evaluation of quality in patient-controlled analgesia provided by an acute pain
      service.
AB  - Institutions with quality management programs need to evaluate the quality of
      perioperative pain management as well as other aspects of the health service.
      With the development of anesthesia-based pain services, improvement in this field
      has been reported. In this prospective study performed in a university hospital,
      we used a Postoperative Pain Therapy Assessment Questionnaire to quantify the
      effectiveness of pain therapy and factors affecting the degree of satisfaction
      and also to pinpoint areas that need improvement. A total of 915 patients who
      received patient-controlled analgesia for postoperative pain were included in the
      study; it seems to be the largest patient population from a single hospital. Data
      were collected as part of the hospital's quality improvement activities. By
      analyzing the questionnaires, we found that patients were satisfied with the pain
      therapy performed under the guidance of anesthesiologists, but predictors of
      satisfaction such as pain intensity and side effects (nausea, vomiting,
      constipation and difficulty in walking) decreased patient satisfaction
      considerably. Patients are aware of the fact that health care givers take
      postoperative care seriously and they do not want any untoward effects
      interrupting their postoperative care. They are trying to participate in the
      decision making and also to learn more about pain medicine.

PMID- 12802097
TI  - Role of granulocyte-macrophage colony-stimulating factor on apoptosis induced by
      ischemia-reperfusion in the intestinal epithelium.
AB  - BACKGROUND: To evaluate the effect of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) on ischemia-reperfusion-induced apoptosis in the intestinal
      epithelium. METHODS: In this study, 50 male Wistar albino rats were used. After
      midline laparotomy superior mesenteric artery (SMA) was identified only in the
      sham group, while 60 min of ischemia and 2 h of reperfusion were performed in the
      control group. In the treatment groups, after 15, 30 and 60 min of ischemia,
      respectively, 1 microg/kg GM-CSF was administered subcutaneously, followed by 2 h
      of reperfusion. Malondialdehyde (MDA), campothecin (CAM), an indicator of DNA
      fragmentation, and histopathology were evaluated in the intestinal mucosa.
      RESULTS: Tissue MDA levels were found significantly high in all groups at various
      times of ischemia and 2 h of reperfusion compared with the sham group (p <
      0.001). Administration of GM-CSF following 60 min of ischemia caused a
      significant increase in the MDA levels compared with the control group (6430 +/-
      725 vs. 4174 +/- 565 nmol/g protein for jejunum. 7576 +/- 618 vs. 4938 +/- 809
      nmol/g protein for ileum, p < 0.05). Intestinal ischemia and reperfusion resulted
      in a significant increase in tissue CAM levels (p < 0.05). The highest CAM value
      was found in the group in which 60 min of ischemia and 2 h of reperfusion were
      performed (50 +/- 3.2 ng/ml for jejunum, 52.8 +/- 2.7 ng/mg for ileum). Compared
      with the control group, GM-CSF administration following 1 h of ischemia
      aggravated the tissue injury. CONCLUSIONS: Apoptosis was induced in the small
      intestine by ischemia-reperfusion. GM-CSF increased the apoptosis of intestinal
      epithelial cells and exacerbated mucosal injury due to ischemia-reperfusion.

PMID- 12802099
TI  - Experimental study using PTFE (Goretex) patches for replacement of the
      oesophageal wall.
AB  - BACKGROUND: The purpose of this study was to evaluate tolerance and integration
      of expanded polytetrafluoroethylene patches used to replace loss of a fragment of
      the complete oesophageal wall in rats of the Wistar strain. METHODS: The
      experiment was performed on 10 Wistar rats. Those surviving the experiment were
      killed 7-28 days after surgery. RESULTS: None of these animals showed signs of
      peritonitis. The patch was not visible macroscopically. After examination under
      the microscope, we observed that the material had undergone phagocytosis by
      macrophages, and there was scar tissue covering the epithelium. CONCLUSION: It is
      possible to successfully suture a polytetrafluoroethylene patch to the
      oesophageal wall in Wistar rats as a prosthetic replacement of a wall fragment.

PMID- 12802100
TI  - 'On-line' alterations of contralateral jugular blood gas profile during carotid
      clamping.
AB  - The aim of this work was to record the metabolic status of the brain (pH, PCO(2)
      and PO(2)) during carotid endarterectomy (CEA), with the use of an intravascular
      multiparameter sensor (Paratrend 7) via retrograde catheterization of the
      contralateral jugular vein. Twenty-four patients with ASA grades II and III
      scheduled for CEA were included in the study. After induction of anesthesia, the
      contralateral internal jugular vein was punctured retrogradely and the sensor was
      introduced. During clamping, pH became persistently more acidotic (7.34-7.31; p <
      0.05), PCO(2) was elevated (43.2-46.8 mm Hg; p < 0.05) while most of the patients
      showed a non-significant decrease in PjvO(2)/SjvO(2) (jv = jugular venous).
      Correlation with clamping time or stump pressure was not significant. Unclamping
      was followed by a short period (5- 9 min) of decrease in pH and elevation of
      PCO(2) (7.30-7.22; p < 0.05, and 48.0-52.5 mm Hg; p < 0.05, respectively).
      PjvO(2) was significantly elevated (51.8-58.0 mm Hg; p < 0.001) after the
      restoration of flow. The study suggests that local CO(2) creates conditions for
      compensation of flow after the application of a carotid clamp. We consider that
      this monitoring technique, after further validation, may provide useful
      information.

PMID- 12802101
TI  - Is intraluminal clip application an appropriate treatment for iatrogenic gastric
      perforation?
AB  - BACKGROUND: The standard treatment of iatrogenic perforation has been an urgent
      operation. Recently, endoscopic clip application was recommended particularly for
      iatrogenic perforations. This study was designed to investigate the usage of
      surgical clips for gastric perforations. METHOD: Forty male rats were allocated
      to four groups. Following a midline laparotomy, a 5-mm gastrotomy was made at the
      fundic part of the stomach and through this ostomy a pre-pyloric perforation was
      created in all groups. In group I, the perforation site was closed with
      polypropylene sutures. In group II, the perforation site was closed
      extraluminally by vascular surgical clips. In group III, the perforation site was
      closed intraluminally by the same number of clips. In group IV, control group,
      the perforation site was left open. The animals were sacrificed on the 4th
      postoperative day. The healing of the perforation site was evaluated by the
      bursting pressure and the hydroxyproline content of the suture line. RESULTS:
      Measurements revealed no differences in bursting pressure and hydroxyproline
      levels between the intraluminal clip application group (group III) and the group
      in which the perforation site was left open (group IV) (p > 0.05). Higher
      bursting pressures and hydroxyproline levels were observed in groups I and II
      compared to control group (p < 0.05). CONCLUSIONS: These results suggest that
      gastric perforations are not strengthened by intraluminal clip application.
      Further detailed clinical studies are necessary in order to conclude that
      intraluminal clip application is an appropriate treatment for iatrogenic
      perforation.

PMID- 12802103
TI  - The impact of intestinal ischaemia-reperfusion on caerulein-induced oedematous
      experimental pancreatitis.
AB  - BACKGROUND: Intestinal ischaemia is a feature of severe acute pancreatitis. It is
      not known whether intestinal ischaemia and reperfusion contributes to the
      progression from mild to severe pancreatitis. AIM: The aim of this study was to
      examine the impact of intestinal ischaemia-reperfusion on caerulein-induced
      oedematous experimental pancreatitis. METHOD: Male Wistar rats (n = 48) were
      randomised to 6 experimental groups: controls (CO), saline infusion (S), saline
      infusion and intestinal ischaemia-reperfusion (SIR), caerulein infusion (C),
      caerulein and sham operation (CS), and caerulein infusion with intestinal
      ischaemia reperfusion (CIR). Caerulein was infused over 6 h to induce mild
      oedematous pancreatitis. Clamping the superior mesenteric artery for 10 min
      induced mild intestinal ischaemia. The reperfusion time was 24 h. The primary end
      point was histology of the pancreas at 24 h. RESULTS: There was no significant
      difference in histologic severity of pancreatitis at 24 h (Kruskal-Wallis, p =
      0.37). CONCLUSION: The severity of acute oedematous pancreatitis was not
      increased by 10 min of intestinal ischaemia followed by 24 h of reperfusion.

PMID- 12802102
TI  - Omental transposition decreases ischemic brain damage examined in a new ischemia
      model.
AB  - PURPOSE: The aim of this study was to determine whether omental transposition at
      the time of focal cerebral ischemia can decrease ischemic brain damage produced
      in dogs, in a new ischemia model, which had been described by us. METHODS: In
      group 1 (n = 5), the left internal carotid artery and arterial circle of the
      brain (posterior communicating artery in humans) were occluded permanently. In
      group 2 (n = 5), additionally to this ischemia model, omental transposition was
      performed simultaneously. In the postoperative early period (first 24 h), single
      photon emission computed tomography (SPECT) and in the late period (72-96 h)
      SPECT and magnetic resonance imaging (MRI) of the brain were performed. Mann
      Whitney U, paired t and Wilcoxon signed rank tests were used for statistical
      analyses, and p < 0.05 was considered significant. RESULTS: The dogs had a
      neurological score (NS) of 3.6 +/- 0.5 and 3.4 +/-0.5 in groups 1 and 2,
      respectively, in the early period (p > 0.05). In the late period, the dogs had an
      NS of 4.4 +/- 0.5 and 5.6 +/- 0.5 in groups 1 and 2, respectively (p < 0.05). The
      NS of each group differed significantly between the early and late period (p <
      0.05). Early SPECT imaging showed 50 +/- 7.0% and 52 +/- 8.4% hypoperfusion
      corresponding to the left middle cerebral artery territory in groups 1 and 2,
      respectively (p > 0.05). In the late period, the degree of hypoperfusion
      decreased to 34 +/- 5.5% and 12 +/- 4.8% in groups 1 and 2, respectively (p <
      0.05). The degree of hypoperfusion in both groups changed significantly between
      the early and late period (p < 0.05). In T(1)- and T(2)-weighted MRI images, the
      volume of the lesion in group 1 was significantly greater than in group 2 (p <
      0.001). CONCLUSION: In our new ischemia model, simultaneous omental transposition
      is helpful in reversing the neurologic deficit and cerebral ischemic damage.

PMID- 12802104
TI  - Productivity, time management--right!

PMID- 12802105
TI  - A mothers orders: hide nothing.

PMID- 12802106
TI  - Back to basics: the Medicare Plan of Care.
AB  - The home health Plan of Care (POC) provides the primary means of communication
      among care providers, is used by regulatory bodies to assess many aspects of
      compliance, and serves as the road map for care delivery. This article focuses on
      requirements for Medicare POC that assure specificity, comprehensiveness, detail,
      and measureable goals.

PMID- 12802107
TI  - New OASIS Q&A's From the 2003 CMS OEC Conference: Part 1--M0010-M0430.

PMID- 12802109
TI  - A primer on ICD-9-CM coding.
AB  - Complete and accurate ICD-9-CM coding is important because coded data are used
      for a variety of purposes. This article provides a primer for home care
      clinicians and managers to master this essential function.

PMID- 12802110
TI  - How a wound resource team saved expenses and improved outcomes.
AB  - The authors describe how the Visiting Nurse Service of New York developed an
      interdisciplinary wound resource team, based on the need to integrate new wound
      care research and products and prepare for PPS. Outlining the change process, the
      reader can learn the dynamics, benefits, and outcomes of effective team
      collaboration that could be replicated in any agency.

PMID- 12802111
TI  - Medication management: an evidence-based model that decreases adverse events.
AB  - Four diverse home care agencies are implementing a new Medication Management
      Model that has proven effective in preventing medication errors in elderly
      patients. The Model, available to all agencies, consists of advice from a
      consultant pharmacist to the attending nurse based on established guidelines. The
      Model's benefits for clinicians, agencies, and patients and how agencies can use
      it are described in this article.

PMID- 12802112
TI  - Recent court rulings.

PMID- 12802114
TI  - The effectiveness of a "restorative" model of care for home care patients.

PMID- 12802115
TI  - Project CHARM: an HIV prevention program for adolescent mothers.
AB  - Effects were examined of a human immunodeficiency virus (HIV) prevention program
      for adolescent mothers offered in pregnant minor and parenting programs in Los
      Angeles County. The sample included young women (N = 497) of predominantly poor,
      Latina backgrounds who had complete data from baseline to the one-year follow-up.
      The treatment group demonstrated statistically significant improvements in AIDS
      knowledge and intentions to use condoms, and fewer sex partners at the six-month
      follow-up as compared to the control group. Findings related to the effects of
      the intervention on theoretical variables provide some support for selected
      concepts from Social Cognitive Theory and the Theory of Reasoned Action.

PMID- 12802116
TI  - An ethnically sensitive and gender-specific HIV/AIDS assessment of African
      American women: a comparative study of urban and rural American communities.
AB  - A prevention program that promotes attitudinal and behavioral change has been
      repeatedly recommended as an effective measure for community prevention and
      control of HIV/AIDS. Within the past decade, disease control programs among
      African Americans have shown no significant changes, as HIV/AIDS and related
      infections continue as the leading causes of death and disability in this
      population. It is particularly acute among African American females who, although
      representing only 13.9% of the United States female population, presently account
      for over 60% of all AIDS cases among females in the United States. The epidemic
      nature of the disease in this group poses the issue of African American women's
      rights and underscores their physical, emotional and sociocultural vulnerability
      to HIV/AIDS. This study used an open-ended attitude, knowledge, feelings, and
      behavior questionnaire (AKFBQ) survey approach to assess knowledge and various
      HIV/AIDS high-risk attitudinal and behavioral factors that affect the incidence,
      mortality, and morbidity of HIV/AIDS among women in specific urban centers and
      rural communities in the United States. Data analysis showed no differences in
      factors favoring rate of infection and level of spread of HIV/AIDS among the
      women in both the urban and rural communities. Although level of knowledge was
      higher among the urban subjects than rural ones, their beliefs,
      attitude/feelings, and potential for behavioral change did not differ
      significantly among women in the two communities. This article advocates both an
      ethnically sensitive and gender-specific HIV/AIDS intervention program for
      African American women and a more active involvement in and participation of
      African American leaders, parents, and faith-based communities in AIDS control
      efforts for African Americans.

PMID- 12802117
TI  - The relationship between eating disorder attitudes and the risk of cardiovascular
      disease.
AB  - The purpose of this study was to examine the relationship between eating disorder
      (ED) attitudes and the risk of cardiovascular disease (CVD). Forty women (M age =
      18.85) agreed to participate in this study. A regression analysis was used to
      statistically examine this relationship. The criterion variable was the risk of
      CVD. The predictor variables were the Eating Disorder Inventory-2 subscales.
      Drive for thinness and body dissatisfaction accounted for 45% (adjusted R(2)
      =.449) of the variance in the participant's CVD risk score. The knowledge gained
      from this study of this relationship would be beneficial to health care
      professionals responsible for primary and secondary prevention.

PMID- 12802119
TI  - Relationships between cigarette smoking and weight control in young women.
AB  - While multiple risk factors are associated with smoking, body weight concern is a
      significant risk factor for smoking among young women, including adolescents.
      This article explores the relationship between frequency of smoking and weight
      loss strategies among a nationally representative sample of high school females
      (n = 7,828). Adjusted odds ratios were generated for smoking, weight goals, and
      weight loss strategies, controlling for demographics. Daily smokers were two to
      four times more likely to fast, use pills, and purge to control their weight than
      nonsmokers. Tobacco control efforts for young women must address the influence of
      weight concern on smoking in this population.

PMID- 12802118
TI  - Breast and cervical cancer screening practices among Hispanic and non-Hispanic
      women residing near the United States-Mexico border, 1999-2000.
AB  - This study examined the breast and cervical cancer screening practices of
      Hispanic and non-Hispanic women (n = 3,568) in counties that approximate the US
      southern border region. According to the Health Resources Services Administration
      (HRSA), border counties are those in which any part of the county is within 100
      kilometers (62.14 miles) of the border. The study used data from Behavioral Risk
      Factor Surveillance System (BRFSS) surveys of adults aged > or = 18 years
      conducted in 1999 and 2000. The study looked at recent use of mammography and the
      Papanicolaou (Pap) test. Hispanic women were less likely to have had a recent
      mammogram or Pap test as compared with non-Hispanic women in border counties, and
      as compared with Hispanic and non-Hispanic women in nonborder counties of Texas,
      New Mexico, Arizona, and California combined, and with other women in the United
      States. Results underscore the need for continued efforts to ensure that
      medically underserved women who live in the border region have access to cancer
      screening services.

PMID- 12802120
TI  - Attachment experiences in women with breast cancer.
AB  - Research into relational experiences of cancer patients suggests possible links
      between attachment processes and cancer. Women with and without breast cancer
      were assessed regarding attachment history and early loss, closeness to parents,
      and adult attachment. Women with breast cancer reported significantly higher
      incidences of insecure histories and early loss, and scored significantly higher
      on avoidant attachment than women without cancer. The women in the cancer group
      also scored significantly lower on closeness to parents than women in the
      noncancer group. These findings are preliminary and indicate that more research
      is needed to understand the role that attachment may play in a multidimensional,
      biopsychosocial model of cancer.

PMID- 12802121
TI  - Jails as important but constrained venues for addressing women's health.
AB  - Women in US jails have many social and health risks that merit attention from
      public health agencies. This article: (1) reviews national and local data on this
      population for indicators of social disadvantage and of several health
      risks/conditions (substance abuse, risky sex, and mental illness), (2) describes
      the impact of federal mandatory sentencing for drug violations and recent
      developments in states on the numbers of incarcerated women, (3) outlines the
      similarities and differences between jails and prisons, focusing on
      characteristics of jails that facilitate and constrain intervention and
      evaluation activities, and (4) adds lessons learned in six years of experience in
      county and state jails in Texas.

PMID- 12802124
TI  - Surviving breast cancer: the role of complementary therapies.
AB  - Early detection and efficacious treatment have prolonged the lives of women
      diagnosed with breast cancer. Although many of these women have survived more
      than 5 years, there is minimal knowledge of their use of complementary and
      alternative medical (CAM) treatments. A qualitative focus group study was
      conducted with 66 breast cancer survivors, ranging in age from 32 to 85 years,
      with time since diagnosis 2 to 28 years. This article will discuss specific
      reasons breast cancer survivors reported for using CAM, the ways in which breast
      cancer survivors blended these therapies with conventional Western medicine, and
      health care providers' roles in supporting breast cancer survivors' use of CAM
      approaches.

PMID- 12802125
TI  - Mindfulness meditation, anxiety reduction, and heart disease: a pilot study.
AB  - Heart disease is the leading cause of death among Americans each year, yet the
      misperception still exists that cardiovascular disease is not a serious health
      problem for women. Evidence indicates that anxiety contributes to the development
      of heart disease. The primary purpose of this study was to assess the
      effectiveness of Kabat-Zinn's mindfulness-based stress reduction program to
      reduce anxiety in women with heart disease. Anxiety, emotional control, coping
      styles, and health locus of control were compared in a treatment and control
      group of women with heart disease. Post-intervention analyses provide initial
      support for beneficial effects of this program.

PMID- 12802126
TI  - Current status of mind-body interventions for vascular complications of diabetes.
AB  - Impaired peripheral blood flow causes complications, disabilities, expenses, and
      deaths among persons with diabetes mellitus. Many individuals suffer from lower
      extremity pain, reduced functional status, and impaired quality of life. Current
      conventional treatments include lifestyle modification, exercise, medication, and
      surgery. However, these approaches are often impractical or insufficient. Thermal
      biofeedback, however, alone or in conjunction with other mind-body techniques,
      improves peripheral circulation, pain, neuropathy, ulcer healing, ambulatory
      activity, and quality of life. It is noninvasive, inexpensive, and consistent
      with community-based approaches to diabetes self-management. As an adjunct to the
      medical management of diabetes, thermal biofeedback may help ameliorate some of
      the vascular complications.

PMID- 12802127
TI  - The role of complementary and alternative therapies in managing rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that is
      characterized by joint stiffness in the morning, symmetric joint swelling, and
      generalized fatigue. Given the limitations of medical treatment and the ongoing
      problems with symptom management, it is not at all surprising that many
      individuals with RA turn to complementary and alternative medicine (CAM)
      therapies. This article provides a brief overview of what is known about CAM use
      in RA, presents information on a few of the most popular therapies, and
      recommends further resources for nurses who work with individuals with RA.

PMID- 12802128
TI  - A holistic programmatic approach to natural hormone replacement.
AB  - With an unprecedented number of women reaching midlife, the impact of menopause
      has become a significant public health issue. Recent findings have left women and
      practitioners questioning traditional hormone replacement therapy (HRT) and
      searching for reasonable alternatives. Growing numbers of women in this country
      are choosing to use natural progesterone and estrogen to treat symptoms of
      menopause. This article describes a program that focuses on education, client
      participation, and alternative methodology to support individualized HRT therapy
      using natural compounded bio-identical hormones.

PMID- 12802129
TI  - Meditation as a complementary therapy in cancer.
AB  - The number of cancer patients seeking complementary therapies to deal with their
      disease has increased steadily in recent decades. Complementary therapies can be
      helpful to cancer patients because they address some of the pervasive
      psychosocial difficulties associated with this disease. One mind-body technique
      is meditation. While programs using meditation have been developed for specific
      health populations, such as heart disease and addictions, an equivalent, well
      established program for cancer patients is lacking. This article reviews the
      literature and proposes a complementary meditation program designed specifically
      for use with cancer patients.

PMID- 12802130
TI  - Association of complementary and alternative medicine use, demographic factors,
      and perimenopausal symptoms in a multiethnic sample of women: the ENDOW study.
AB  - Complementary and alternative medicine (CAM) use is common in the United States,
      particularly among middle-aged women for symptoms commonly reported during
      perimenopause. The study examined the relationship between women's report of
      perimenopausal symptoms and the use of CAM and socioeconomic or cultural factors.
      The prevalence of CAM use was 33%; approximately 94% reported use of CAM
      therapies and 23% used CAM practitioners. Those who used CAM were younger and
      better educated; more often they reported pelvic pain and painful intercourse.
      The only demographic factor to predict use of alternative medicine was education.

PMID- 12802137
TI  - Assessing assets in racially diverse, inner-city youths: psychometric properties
      of the search institute asset questionnaire.
AB  - Asset assessment of adolescents is becoming increasingly common in communities.
      The purpose of this study was to assess the validity and reliability of the
      "Profiles of Student Life," the most commonly used asset assessment
      questionnaire. In this study, 435 Midwestern, inner-city, primarily African
      American (77%) students completed the instrument, with 288 completing it twice
      for stability reliability. Principal components analysis did not support
      construct validity of the categories as identified by the Search Institute. Both
      internal consistency and stability reliabilities were poor to mediocre for the
      various categories. The use of the Profiles of Student Life instrument may not be
      useful in community assessment with inner city, racially diverse populations.

PMID- 12802138
TI  - Assessment of a pilot video's effect on physical activity and heart health for
      young children.
AB  - This article assessed the effects of a video, "Dynamotion," on children's
      knowledge, self-efficacy, and attitude about physical activity and heart health.
      A quasi-experimental design was used; 12 classrooms (grades K-2) were assigned to
      intervention (N = 116) or comparison (N = 92) groups. Students completed a 9-item
      pre- and posttest; only the intervention group was exposed to the video, during
      which qualitative assessments were made. Repeated measures analyses were used to
      detect changes. Overall, the intervention group had greater gains in knowledge
      and self-efficacy than did the comparison group (p < 0.001), and they seemed to
      enjoy the video. The results suggest that exposure to a short, interactive,
      educational video may promote health among young children.

PMID- 12802139
TI  - Assessing the effectiveness of a community-based media campaign targeting
      physical inactivity.
AB  - The goal of this study was to develop, implement, and evaluate a community-based
      effort addressing the problem of physical inactivity. Using Prochaska's
      Transtheoretical Model as a guide, community members developed television and
      worksite media messages focusing on the benefits and barriers of physical
      activity and on increasing self-efficacy. The media campaign was effective in
      changing perceived barriers, perceived benefits, and self-efficacy surrounding
      physical activity and had an unexpected effect of changing behavior. It was
      reasoned that the success of the campaign might have been because of its unique
      local flavor. Seeing local community members participate in physical activity may
      motivate people to comply with the media messages.

PMID- 12802140
TI  - Telehealth for elders and their caregivers in rural communities.
AB  - The use of technological strategies in providing care for patients and their
      families at distant locations has been available since the 1950s. Today's
      telehealth approaches are proposed to offer considerable promise for enhanced
      service delivery in rural and other underserved communities. Technology-based
      delivery methods, such as videophone skill training, and one- and two-way
      interactive computer networks, are envisioned as contributors for improving rural
      residents' access to services, individualizing rural health care, increasing
      rural health practitioners' continuing education opportunities, and improving
      quality and cost-efficiency of care.

PMID- 12802141
TI  - Faith community nursing: parish nursing/health ministry collaboration model in
      central Texas.
AB  - Collaboration provides a unique opportunity for a variety of people and
      organizations to promote faith community nursing. With emphasis on holistic
      nursing, stewardship, and interpreting the dialogue between faith and health,
      educated nurses acting as health educators, planners, and counselors can aid in
      meeting the health needs and in promoting the well-being of their faith
      communities.

PMID- 12802142
TI  - MDON: a network of community partnerships.
AB  - This model for strengthening diabetes care in communities teams the public health
      system with the professional and lay community to address prevention, early
      detection, and treatment of diabetes. This article describes how the Michigan
      Diabetes Outreach Network (MDON) develops local, regional, and statewide
      partnerships to increase professional and public knowledge and to improve care
      delivery for this chronic and complex disease.

PMID- 12802143
TI  - A community-based free nursing clinic's approach to management of health problems
      for the uninsured: the hepatitis C example.
AB  - Poverty, as an outgrowth of lack of opportunity in employment, basic education,
      affordable housing, and racism, directly affects disparities in health status.
      Health care providers are challenged to identify and overcome systemic barriers
      to health services for the poorest patients. This article describes the
      population of patients and the model of care offered by the Wald Community
      Nursing Center, a free nurse-managed clinic in Baltimore, Maryland. Hepatitis C
      infection is used to illustrate the confounding factors of a costly, chronic
      health problem and the interventions that have been instituted to overcome them.

PMID- 12802144
TI  - Wellness general of the United States: a creative approach to promote family and
      community health.
AB  - This article offers a creative approach to promote family and community health,
      beginning with the conversion of the office of Surgeon General of the United
      States into the Wellness General of the United States. The content ranges from
      federal initiatives to promote quality health research to individuals and
      families who will be the beneficiaries at medical clinics and community health
      programs. The proposal recommends changes to institutions and policies, including
      junk food taxes, the National Institutes of Health, the United States Preventive
      Services Task Force, the Healthy People 2010 initiative, the Health Plan Employer
      Data and Information Set, the Medicare Coverage Advisory Committee, state health
      mandates, local health plans, community medical clinics, and community health
      programs. The goal is to stimulate ideas and actions among policymakers,
      researchers, practitioners, educators, and students.

PMID- 12802146
TI  - Sex, drugs, and marketing.

PMID- 12802147
TI  - Welcome to SARS hell.

PMID- 12802149
TI  - It was a shock.

PMID- 12802150
TI  - Smallpox compensation legislation passes.

PMID- 12802151
TI  - Milagros.

PMID- 12802152
TI  - West Nile virus: a growing challenge.

PMID- 12802153
TI  - Topical local anesthetics.

PMID- 12802154
TI  - Are all syringes created equal?

PMID- 12802155
TI  - Cardiac arrest: the effect on the brain.

PMID- 12802156
TI  - Like a patient etherized upon a table.

PMID- 12802159
TI  - ECT controversy.

PMID- 12802161
TI  - A change of plans.

PMID- 12802162
TI  - Postmenopausal hormone replacement therapy for the primary prevention of chronic
      conditions: recommendations and rationale.

PMID- 12802163
TI  - From the USNS Comfort.

PMID- 12802164
TI  - Scent of a workplace.

PMID- 12802165
TI  - TASIT: A new clinical tool for assessing social perception after traumatic brain
      injury.
AB  - OBJECTIVE: To develop a clinically sensitive test of social perception for people
      with traumatic brain injury (TBI). DESIGN: An assessment tool comprising
      videotaped vignettes and response probes was developed in successive stages and
      tested on both normal participants and those with TBI. SUBJECTS: A total of 169
      normal adults and 7 adults with severe TBI (pilot studies), 283 normal adults,
      and 12 people with severe TBI (main studies). MAIN OUTCOME MEASURES: "The
      Awareness of Social Inference Test" (TASIT) comprises videotaped vignettes of
      everyday social interactions and has three parts, each with alternate forms. The
      Emotion Evaluation Test (EET) assesses recognition of spontaneous emotional
      expression (happy, surprised, sad, anxious, angry, disgusted, and neutral). The
      Social Inference-Minimal (SI-M) test assesses comprehension of sincere versus
      sarcastic exchanges, whereas the Social Inference-Enriched test (SI-E) assesses
      lies versus sarcasm. In both SI-M and SI-E speaker demeanor (voice, facial
      expression) indicate the intended meaning of the exchange. In addition, the SI-E
      vignettes have other contextual clues that reveal the speakers' intentions.
      Performance on SI-E and SI-E is assessed via four standard questions per item
      probing for understanding of the emotions, intentions, beliefs, and meanings of
      the speakers and their exchanges. RESULTS: Groups taken from the pool of 283
      normal adults achieved a high level of performance on all aspects of the test
      with some influence from both education and intelligence. The 12 people with TBI
      were poorer at judging emotions than were matched controls, with particular
      difficulties recognizing neutral items, fear, and disgust. They were as capable
      as matched controls when understanding sincere exchanges and lies but had
      difficulty with sarcasm. CONCLUSIONS: TASIT is straightforward for people with a
      normal range of social skills while being sensitive to social perception deficits
      after traumatic brain injury.

PMID- 12802166
TI  - Incidence, characteristics, and predictive factors for Dysphagia after pediatric
      traumatic brain injury.
AB  - OBJECTIVE: (1) To establish an incidence figure for dysphagia in a population of
      pediatric traumatic brain injury (TBI) cases; (2) to provide descriptive data on
      the admitting characteristics, patterns of resolution, and outcomes of children
      with and without dysphagia after TBI; and (3) to identify any factors present at
      admission that may predict dysphagia. PARTICIPANTS: A total of 1,145 children
      consecutively admitted to an acute care setting for traumatic brain injury
      between July 1995 and July 2000. MAIN OUTCOME MEASURE: Medical parameters
      relating to dysphagia based on medical chart review. RESULTS: (1) Dysphagia
      incidence figure of 5.3% across all pediatric head injury admissions. Incidence
      figures of 68% for severe TBI, 15% for moderate TBI, and only 1% for mild brain
      injury. (2) Statistically significant differences were found between the
      dysphagic and nondysphagic subgroups on the variables of length of stay, length
      of ventilation, Glasgow Coma Scale (GCS), computed tomography classification,
      duration of speech pathology intervention, supplemental feeding duration,
      duration until initiation of oral intake (DIOF), duration to total oral intake
      (DTOF), and period of time from the initiation of intake until achievement of
      total oral intake (DI-TOF). (3) Significant predictive factors for dysphagia
      included GCS < 8.5 and a ventilation period in excess of 1.5 days. CONCLUSION:
      The provision of incidence data and predictive factors for dysphagia will enable
      clinicians in acute care settings to allocate resources necessary to deal with
      the predicted number of dysphagia cases in a pediatric population, and assist in
      predicting patients who are at risk for dysphagia following TBI. Early detection
      of patients with swallowing dysfunction will be aided by these data, in turn
      helping to facilitate effective medical and speech pathology intervention via
      assisting the reduction of medical complications such as aspiration pneumonia.

PMID- 12802167
TI  - Reliability of ratings on the Glasgow Outcome Scales from in-person and telephone
      structured interviews.
AB  - OBJECTIVE: To determine test-retest reliability and interrater reliability for
      structured interviews for the Glasgow Outcome Scale (GOS) using in-person and
      telephone contact. METHODS: Study 1: Thirty head-injured patients were
      interviewed face-to-face and then reinterviewed by telephone a few days later by
      the same rater. Study 2: Fifty-six head-injured patients were interviewed by
      telephone and then face-to-face interviews were carried out by a different person
      up to 1 month later. Agreement between ratings on the GOS and the extended GOS
      (GOSE) in each of the studies was assessed using the kappa statistic weighted
      with quadratic weights. RESULTS: Values of kappa(w) for the test-retest
      reliability study were.92 for both GOS and GOSE, and for interrater reliability
      study were.85 for the GOS and.84 for the GOSE. CONCLUSIONS: The findings indicate
      good test-retest and interrater reliability for the structured interviews. In
      most circumstances a structured interview over the telephone can provide a
      reliable assessment of the GOS, and can safely be substituted for in person
      contact.

PMID- 12802168
TI  - Constraint-induced movement therapy for hemiplegic children with acquired brain
      injuries.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of constraint-induced
      movement therapy (CIMT) for impaired upper extremity (UE) function in children
      with acquired brain injury (ABI). DESIGN: Multiple case studies. SETTING:
      Inpatient pediatric rehabilitation. PARTICIPANTS: Seven consecutive ABI
      rehabilitation admissions with hemiparesis were recruited without regard to
      injury etiology, age, or cognitive capacities. MAIN OUTCOME MEASURE: The actual
      amount of use test (AAUT) was used to evaluate change in UE function. AAUT amount
      of use (AOU) and quality of movement (QOM) scales were obtained at baseline and
      follow-up. RESULTS: AOU and QOM item improvements were significant, as were
      changes in activities of daily living. The effect sizes for these changes were
      large. CONCLUSIONS: Stringent CIMT training, previously only implemented with
      adults, can be used effectively with children when everyday elements of a child's
      life are integrated into adult protocols. The use of child-friendly UE shaping
      exercises, "pushed into" activities by professional therapists as well as trained
      teachers, paraprofessionals, and parents, was supported. Effects of impairment,
      injury, and behavior on outcomes are discussed. Larger controlled studies with
      additional outcome measures are indicated.

PMID- 12802169
TI  - Perceptual and instrumental analysis of laryngeal function after traumatic brain
      injury in childhood.
AB  - OBJECTIVE: To investigate laryngeal function and phonatory disturbance in
      children with traumatic brain injury (TBI), using both perceptual and
      instrumental techniques. DESIGN AND PARTICIPANTS: The performance of 16
      individuals with moderate to severe TBI acquired in childhood and 16
      nonneurologically impaired control subjects was compared on a battery of
      perceptual (Frenchay Dysarthria Assessment, speech sample analysis) and
      instrumental (Aerophone II, laryngograph) assessments. RESULTS AND CONCLUSIONS:
      As a group, the children with TBI demonstrated normal, or only minimally impaired
      laryngeal function, when compared with the control group, which contrasts with
      the significant laryngeal impairment noted in adults after TBI. Several reasons
      for the different findings in relation to laryngeal function in adults and
      children after TBI are postulated: (1) differing types of injury usually incurred
      by adults and children may result in a relatively decreased degree of neurologic
      impairment in these children, (2) differences in recovery potential between
      adults and children, and (3) the pediatric larynx is still developing, hence it
      may be better able to compensate for any impairment incurred.

PMID- 12802170
TI  - The use of the BNI screen for higher cerebral functions in assessing
      disorientation after traumatic brain injury.
AB  - OBJECTIVE: To examine the use of the Barrow Neurological Institute Screen for
      Higher Cerebral Functions (BNIS) in assessing disorientation in patients with
      traumatic brain injury (TBI) during the acute phases of rehabilitation. DESIGN:
      Persons with TBI (n = 65) were compared with patients with spinal cord injury
      (SCI; n = 18) and to controls (n = 35). SETTING: Inpatient neurorehabilitation
      unit. OUTCOME MEASURES: Orientation items from the BNIS measuring time (day,
      month, date of month, year) and place (city and hospital). RESULTS: TBI patients
      showed a significantly greater proportion of incorrect responses to time and
      place compared with the SCI and normal control groups. There was a greater
      accuracy on orientation to place compared with orientation to time, and date of
      month produced the lowest rate of accuracy in all three groups. The single best
      predictor of disorientation to time was increasing age, and increasing age was
      most associated with disorientation to date of month. CONCLUSIONS: The BNIS was
      shown to be a sensitive measure of disorientation in TBI patients and yielded
      similar patterns of performance as documented by other measures.

PMID- 12802171
TI  - North Star Project: reality orientation in an acute care setting for patients
      with traumatic brain injuries.
AB  - OBJECTIVE: The North Star Project is an acute care rehabilitation approach for
      patients with moderate and severe traumatic brain injuries. This patient-centered
      project uses the concepts of Reality Orientation Therapy to develop a unique
      approach that focuses "environment," "consistency" and "standardization" to
      promote a total team effort. Patients, treatment staff and members of the
      patient's family collaborate in a unified bedside protocol that stimulates
      orientation, encourages patients' appropriate interactions and aims to decrease
      the length of post-traumatic amnesia. Development of materials, protocols,
      training and outcome measurement initiatives are described.

PMID- 12802173
TI  - Taste transduction: appetizing times in gustation.
AB  - Taste receptors cells sample the chemical composition of ingested material in
      order to provide the initial sensory information to facilitate decisions
      regarding its eventual acceptance or rejection. Ion channels, ionotropic and
      metabotropic receptors have been implicated in the initial events of transduction
      but until recently their identification has proven difficult. Recent advances in
      the identification and functional characterization of mammalian taste receptors
      has greatly increased our understanding of the pathways for the transduction of
      taste stimuli. This basic information will be critical to answer longstanding
      questions regarding the coding of taste information and may help elucidate the
      role of the taste system in the control of food intake.

PMID- 12802174
TI  - Selectively reduced regional cortical volumes in post-traumatic stress disorder.
AB  - Different subterritories of anterior cingulate cortex (ACC) and adjacent
      ventromedial frontal cortex have been shown to serve distinct functions. This
      scheme has influenced contemporary pathophysiologic models of psychiatric
      disorders. Prevailing neurocircuitry models of post-traumatic stress disorder
      (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as
      well as amygdala and hippocampus. In the current study, cortical parcellation of
      magnetic resonance imaging data was performed to test for volumetric differences
      in pregenual ACC and SC, between women with PTSD and trauma-exposed women without
      PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC
      volumes. These results are consistent with contemporary schemes regarding
      functional and structural dissection of frontal cortex, and suggest specific
      regional cortical pathology in PTSD.

PMID- 12802175
TI  - Long-lasting induction of Notch2 in the hippocampus of kainate-treated adult
      mice.
AB  - Notch proteins are involved in cell fate specification during development in
      tissues including brain. Little is known about their function in adulthood.
      Recently, Notch receptors have been hypothesized to play a role in
      neurodegeneration and in particular in Alzheimer's disease (Notch1) and CADASIL
      (Notch3). Here we show that another family member (Notch2) is constitutively
      expressed in adult mouse hippocampus in DG and not in CA1 and CA3 neurons.
      Treatment with kainic acid resulted in marked Notch2 induction in pyramidal
      neurons of CA1 and in a subpopulation of CA3 neurons surviving the lesion and
      protein expression was still detectable 6 weeks after drug treatment. These
      results suggest Notch2 involvement in the response of postmitotic neurons to
      excitotoxic stimuli.

PMID- 12802176
TI  - Error-rate-related caudate and parietal cortex activation during decision making.
AB  - The role of cortical and subcortical structures in processing success or failure
      in decision-making situations is unclear. Functional neuroimaging (fMRI) during a
      two-choice prediction task was used to investigate the relationship between error
      rate-related behavioral changes during decision-making and activation patterns in
      the caudate and parietal cortex. Success-related activation was found in caudate
      and parietal cortex during a two-choice prediction task. At low error rates,
      participants utilized success-related behavioral strategies rate by decreasing
      switching responses and increasing response predictability, which were associated
      with activation changes in the caudate and parietal cortex. Therefore, less
      response switching and increased response predictability during decision making
      can be directly related to the degree of activation in the caudate and posterior
      parietal cortex.

PMID- 12802177
TI  - Differential subcellular localization of phosphorylated neurofilament and tau
      proteins in degenerating neurons of the human entorhinal cortex.
AB  - A panel of novel monoclonal antibodies was tested on the human entorhinal cortex
      for the recognition of age- and disease-related changes of neurofilament proteins
      (NF). Several antibodies identified phosphorylated NF-H subunit, which occurred
      preferentially in those aged between 60 and 80 years and were localized in
      degenerating neurons. Such neurons also contained neurofibrillary tangles, but
      neurofilament aggregates did not co-localize with tangles, nor did the quantity
      nor the number of NF-positive neurons correlate with the severity of Alzheimer's
      disease. This points to a susceptibility of NF in a subset of neurons for
      phosphorylation- and metabolically related morphological changes during
      neurodegeneration.

PMID- 12802178
TI  - Reduction but not cleavage of poly(ADP-ribose) polymerase during stress-mediated
      cell death in the rat hippocampus.
AB  - Sustained stress induces neuronal atrophy and death, especially in the
      hippocampus, which impairs hippocampal function. However, underlying mechanisms
      of stress-induced neuronal damage have not been precisely defined. We analyzed
      the molecular events related to apoptosis in the hippocampus of rats exposed to
      immobilization stress. Terminal dUTP nick end-labeling exhibited positive nuclei
      in the hippocampus of stressed rats, indicating DNA fragmentation. RT-PCR and
      Western blot analyses showed that immobilization stress increased and decreased
      the expression of pro-apoptotic gene bax and anti-apoptotic bcl-2 genes,
      respectively. Western blot analysis demonstrated that the characteristic 85 kDa
      apoptotic fragment of poly(ADP-ribose) polymerase (PARP) was not observed in the
      hippocampus subjected to immobilization stress. The amount of PARP protein was
      significantly reduced following stress. This study may provide a novel insight
      into molecular mechanisms implicated in hippocampal damage associated with
      stress.

PMID- 12802179
TI  - JNK pathway is required for retinoic acid-induced neurite outgrowth of human
      neuroblastoma, SH-SY5Y.
AB  - Neurite outgrowth is a central event of neuronal differentiation that proceeds in
      multiple processes requiring various cellular factors. Here we demonstrated that
      c-Jun N-terminal kinase 1 (JNK1) plays an essential role in RA-induced neurite
      outgrowth of SH-SY5Y cells. Treatment of SH-SY5Y cells with RA induced a strong
      activation of JNK1 within 10 min, and the immediate increase of JNK1 activity
      returned to the basal level in an hour. The second surge of JNK1 activity was
      observed around 1 day after RA treatment, which coincided with the period of
      extensive neurite outgrowth. Interestingly, phospho-JNK was concentrated in the
      nucleus of cells during the early induction, whereas it was distributed into
      neurite processes during the delayed second activation period. In SH-SY5Y
      carrying a dominant negative form of SEK1, an upstream kinase of JNK1, both early
      and late inductions of JNK1 activity were repressed along with RA-induced neurite
      outgrowth. These results suggest that JNK1 plays an essential role in RA-induced
      neuronal differentiation of SH-SY5Y cells.

PMID- 12802180
TI  - Differential expression patterns of mGluR1 alpha in monkey nigral dopamine
      neurons.
AB  - The expression pattern of metabotropic glutamate receptor 1alpha (mGluR1alpha)
      was immunohistochemically investigated in substantia nigra dopaminergic neurons
      of the macaque monkey. In normal monkeys, mGluR1alpha immunoreactivity was weakly
      observed in the dorsal tier of the substantia nigra pars compacta (SNc-d) where
      calbindin-D28k-containing dopaminergic neurons invulnerable to parkinsonian
      degeneration are specifically located. On the other hand, mGluR1alpha was
      strongly expressed in the ventral tier of the substantia nigra pars compacta (SNc
      v). In monkeys treated with the parkinsonism-inducing drug, 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP), mGluR1alpha expression was decreased in
      dopaminergic neurons in the SNc-v that were spared its toxic action. These
      results suggest that mGluR1alpha expression may be involved at least partly in
      the vulnerability of dopaminergic neurons to parkinsonian insults.

PMID- 12802181
TI  - DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the
      primate brain.
AB  - Disrupted in Schizophrenia-1 (DISC1) was identified as truncated by a balanced
      translocation segregating with schizophrenia and other major mental illness in a
      large Scottish family. As a step in evaluating the function of DISC1 and its
      potential role in human schizophrenia, we have determined its regional expression
      in the primate brain by in situ hybridization. DISC1 expression is highly
      localized, with most prominent expression in the dentate gyrus of the hippocampus
      and lateral septum, and lower levels of expression in the cerebral cortex,
      amygdala, paraventricular hypothalamus, cerebellum, interpeduncular nucleus, and
      subthalamic nucleus. Given that many of these regions have been implicated in
      schizophrenia pathogenesis, these results suggest brain circuits through which
      DISC1 truncation may predispose to schizophrenia.

PMID- 12802182
TI  - Faces evoke spatially differentiated patterns of BOLD activation and
      deactivation.
AB  - Using fMRI techniques sensitive to blood oxygen-level dependent (BOLD) contrast,
      we measured brain activity in participants (n=8) as they viewed images of faces
      presented periodically within a continuously changing montage of common objects.
      Consistent with prior studies, we identified regions of ventral extrastriate
      cortex, primarily in the fusiform and inferior temporal gyri and nearby cortex,
      that were activated by faces as measured by an increase in BOLD signal. In
      addition, we made the novel observation that faces deactivated other areas of
      ventral extrastriate cortex, primarily in the lingual and parahippocampal gyri
      and medial to activations. These deactivated regions, identified by a decrease in
      BOLD signal, may reflect populations of neurons that decrease their activity when
      faces appear, possibly as a consequence of category-specific inhibition.

PMID- 12802183
TI  - Localized morphological brain differences between English-speaking Caucasians and
      Chinese-speaking Asians: new evidence of anatomical plasticity.
AB  - Deformation field morphometry was applied to magnetic resonance images to detect
      differences in brain shape between English-speaking Caucasians and Chinese
      speaking Asians. Anatomical differences between these two groups were limited to
      gyri in the frontal, temporal and parietal lobes, which are known (through
      functional imaging studies) to differentiate Chinese speakers from English
      speakers. We interpret these anatomical differences as evidence of neural
      plasticity shaped by the process of language acquisition during childhood. While
      anatomical plasticity due to manual skill acquisition (e.g. in musicians) has
      been established, to our knowledge this is the first report of a brain anatomical
      difference attributable to a learned cognitive strategy.

PMID- 12802184
TI  - Kinetic variability of AMPA receptors among olfactory bulb neurons in culture.
AB  - AMPA receptors, which are composed of four subunits (GluR1-4), help mediate
      synaptic transmission at most excitatory synapses in the brain. Their subunit
      composition influences the kinetics of AMPA receptor deactivation and
      desensitization, thus, the efficacy of synaptic transmission. Immunohistochemical
      data suggest that AMPA receptor subunit expression in the olfactory bulb (OB)
      follows a distinct laminar and cellular distribution. However, little is known
      about the kinetic properties of AMPA receptors on OB neurons. In this study, we
      used kinetic analysis and pharmacologic methods to demonstrate that the rate and
      extent of desensitization of OB AMPA receptors vary within and between neuronal
      subtypes. Such variability suggests that a broad functional diversity of AMPA
      receptors contributes to olfactory information processing.

PMID- 12802185
TI  - Neural correlates of shape from shading.
AB  - Psychophysical studies have shown that human observers resolve shape-from-shading
      ambiguities by assuming that light is coming from above-left. Using event-related
      potentials (ERPs), we measured the processing time of the perception of an
      ambiguous shaded pattern. We found that the N2 component followed the change of
      perceived shape with stimulus orientation. We also found that the P1 component in
      occipital and temporal areas was correlated with the observers' idiosyncratic
      bias for light source position. The precocity of the correlated ERP components
      suggests that the light source is represented early in the visual system.
      Altogether, our results indicate that shape-from-shading is a mostly bottom-up
      mechanism.

PMID- 12802186
TI  - Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks
      treatment.
AB  - Clinical, neurophysiological and neuroimaging data suggest that chronic tinnitus
      resembles neuropsychiatric syndromes characterised by focal brain activation. Low
      frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed
      as an efficient method in treating brain hyperexcitability disorders. In one
      patient suffering from chronic tinnitus, [18F]deoxyglucose PET revealed increased
      metabolic activity in a circumscript area of the left primary auditory cortex
      (PAC). The effect of MRI and PET guided neuronavigated 1 Hz rTMS of this area was
      evaluated in a single-blind, sham-controlled, cross-over manner, followed by a 4
      week open treatment. Following active stimulation there was a remarkable effect,
      enduring several weeks, on tinnitus sensation, which was paralleled by altered
      cortical excitability. These findings suggest that neuronavigated rTMS of
      increased PAC activity might offer a new option for treating auditory phantom
      perceptions like chronic tinnitus.

PMID- 12802187
TI  - The role of the central nucleus of the amygdala in nociception and aversion.
AB  - The role of the central nucleus of the amygdala in nociception--conditioned and
      unconditioned aversion--was studied. Rats received microinjection of vehicle or
      the N-type Ca2+ channel blocker omega-conotoxin GVIA (0.2 microg/250 nl) into the
      central amygdaloid nucleus prior to intra-plantar injection of formalin,
      ultrasound exposure or immediately prior to the acquisition phase of an aversive
      conditioning trial. Intra-amygdala omega-conotoxin GVIA resulted in an earlier
      onset of nociceptive response to formalin and increased nociceptive behaviour
      during the first 5 min. Omega-conotoxin GVIA significantly reduced conditioned
      freezing behaviour with no effect on ultrasound-induced unconditioned aversive
      behaviour. These data indicate that N-type Ca2+ channels in the central
      amygdaloid nucleus play a role in mediating behavioural responses to nociceptive
      and conditioned aversive stimuli.

PMID- 12802188
TI  - Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to
      colorectal distention.
AB  - The purpose of this study was to examine the effect of cutaneous inflammation on
      the responses of viscerosomatic convergent dorsal horn neurons to graded
      colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of
      single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to
      CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous
      inflammation induced by intradermal injection of capsaicin in the receptive field
      (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the
      RF induced an increase in the spontaneous activity of dorsal horn neurons, an
      expansion in the size of their RF and facilitated their responses to cutaneous
      stimuli. An injection placed in the center of the RF attenuated the responses to
      noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in
      the responses to CRD but not to cutaneous stimuli. These results indicate that
      the inhibitory effects, evoked by cutaneous inflammation, can modulate the
      responses of dorsal horn neurons to CRD, independent of its effect on the
      responses to cutaneous mechanical stimuli.

PMID- 12802189
TI  - Extracellular glutamate decrease in accumbens following cued food delivery.
AB  - This study examined the effects of cued vs non-cued food delivery/consumption on
      extracellular glutamate and dopamine in the nucleus accumbens of food-deprived
      rats. Animals that always received a food pellet following a series of auditory
      tones showed a significant decrease in extracellular glutamate following food
      consumption, whereas animals that had not been previously exposed to tone-food
      pairing did not (p<0.05). In contrast, extracellular dopamine was significantly
      increased in the nucleus accumbens during the first time period after food
      consumption (p<0.05) regardless of whether animals had been exposed to prior tone
      food pairing. Results suggest that food delivery/consumption is associated with a
      decrease in accumbal glutamate if food delivery has been previously paired with
      predictive environmental cues.

PMID- 12802190
TI  - CEP-1347 promotes survival of NGF responsive neurones in primary DRG explants.
AB  - CEP-1347 inhibits the signalling pathway of c-jun-N-terminal kinase, and is
      neuroprotective in vivo and in vitro. Embryonic chick dorsal root ganglion
      neurones are dependent on NGF for survival and neurite outgrowth; NGF withdrawal
      results in apoptotic cell death. We examined the neuroprotective and neurite
      outgrowth promoting activity of CEP-1347 in dissociated DRG neurones and in
      primary DRG explants. CEP-1347 was as effective as NGF in promoting survival of
      dissociated DRG neurones, but caused only limited neurite outgrowth from DRG
      explants. When NGF was subsequently added to CEP-1347 treated explants, the
      outgrowth increased to a similar level to explants which had received NGF
      throughout. CEP-1347 may be a useful tool to maintain viable DRG explants to
      allow evaluation of neurite outgrowth promoting compounds and dissection of
      survival and neurite outgrowth signalling pathways.

PMID- 12802191
TI  - Oligodendroglial-derived stress signals recruit microglia in vitro.
AB  - Rat oligodendrocytes cultured without the essential survival factors serum and
      insulin die over a 48 h period. Analysis of supernatants from these dying
      cultures reveals a microglial chemokine released in advance of significant cell
      death. The observed microglial chemotactic effect is dose-dependent and not due
      to release of cellular debris. Interferon (IFN)-gamma activated microglia are
      more sensitive to the microglial chemokine. We show in co-culture that recruited
      non-activated microglia can enhance oligodendroglial survival whereas IFN-gamma
      activation of microglia induces contact-dependent oligodendroglial death. Thus,
      whilst the initial recruitment of microglia by stressed oligodendroglia may
      represent part of a survival process engaged by injured cells, this does not
      necessarily ensure survival.

PMID- 12802192
TI  - Phobic postural vertigo: body sway during vibratory proprioceptive stimulation.
AB  - Phobic postural vertigo patients might rely more on proprioceptive than visual
      cues to regulate stance. We tested 14 phobic postural vertigo patients and 24
      healthy subjects with posturography during quiet stance and periods of vibratory
      proprioceptive calf muscle stimulation, both with eyes open and closed. During
      quiet stance phobic postural vertigo patients showed higher torque variance than
      healthy subjects, especially above 0.1 Hz. Vibratory proprioceptive stimulation
      increased the differences between healthy subjects and phobic postural vertigo
      patients. The patients were less able to use vision to counteract vibration
      induced movements. Phobic postural vertigo patients are more sensitive to
      proprioceptive disturbances than healthy subjects are, and less apt to use visual
      information to control upright stance. This might be part of an anxious mode of
      balance control.

PMID- 12802193
TI  - Selective deficit in no-go performance induced by blockade of prefrontal cortical
      alpha 2-adrenoceptors in monkeys.
AB  - Two monkeys (Macaca mulatta) were trained to make a go response (go to touch a
      computer screen) when a red signal (go signal) was presented or a no-go response
      (inhibit the screen-touching action) when a green signal (no-go signal) was
      given. The alpha2-adrenergic antagonist yohimbine was infused locally,
      bilaterally and continuously for 8 days into the prefrontal cortex (PFC) by using
      mini-osmotic pump. The no-go but not go performance was selectively impaired
      during the 8-day administration of yohimbine: the monkeys showed an inability to
      inhibit the touching response to the no-go signal, indicating that there was a
      deficit in the inhibitory ability of the animals. Similar infusion of saline into
      the same cortical area was without effect. The present study provides behavioral
      pharmacological evidence that alpha2-adrenoceptors in the PFC are involved in the
      neural mechanisms underlying response inhibition.

PMID- 12802194
TI  - Effects of morphine on mechanical allodynia in a rat model of central neuropathic
      pain.
AB  - We examined whether morphine reduced the behavioral signs of neuropathic pain
      below level induced by T13 spinal hemisection in rats. In order to examine the
      effect of morphine on the mechanical allodynia, morphine alone, morphine with
      naloxone and saline were administered intraperitoneally and intrathecally and
      behavioral tests were conducted. In systemic injection, mechanical allodynia was
      reduced only when a higher concentration of morphine (5 mg/kg) was used.
      Intrathecally injected morphine (0.5, 1, 2, 5 microg) reduced mechanical
      allodynia dose-dependently. It is suggested that systemic morphine has limited
      effect on mechanical allodynia but direct spinal administration of morphine is
      more effective in controlling central pain following spinal cord injury.

PMID- 12802195
TI  - Increased cortical excitability in human deception.
AB  - Deception is a cognitive process in humans and animals which is not well
      understood. Most studies on lie detection have focused on emotional components
      associated with deception. We employed transcranial magnetic stimulation of the
      motor cortex in conjunction with a constrained question answer protocol for the
      first time to show increased cortical excitability in generating deceptive
      responses, in contrast with truthful responses. This may be due to increased
      cognitive activity in the motor and premotor connections. Our findings
      corroborate functional imaging studies and may have future implications in
      evaluating lie detection.

PMID- 12802196
TI  - Suppression of apoptosis occurs in the cochlea by sound conditioning.
AB  - Apoptosis plays a critical role in the pathogenesis of noise-induced hearing
      loss. The goal of this study was to determine if apoptotic pathways are
      suppressed by sound conditioning. Sound conditioning is a pretreatment to low
      level non-damaging sound that protects against a subsequent damaging acoustic
      trauma. Sound conditioning protects against hair cell death and thereby preserves
      hearing after a subsequent acoustic trauma. Using a combination of
      immunocytochemical and Western blotting techniques we show that acoustic trauma
      causes the release of cytochrome c from the mitochondria into the cytoplasm, and
      a decrease in bcl-2 immunoreactivity in the outer hair cells. Sound conditioning
      was found to trigger a protection against these detrimental changes. These data
      suggest that bcl-2 plays an important role in the regulation of hair cell death,
      and provides evidence that bcl-2 acts as an inducible neuroprotective gene that
      is upregulated by sound conditioning.

PMID- 12802197
TI  - Divergence in the upstream signaling of nerve growth factor (NGF) and epidermal
      growth factor (EGF).
AB  - The early response of mammalian cells to growth factors consists of a combination
      of protein assemblages and kinase cascades. In the study of how signal
      specificity of different growth factors is determined, PC12 cells represent an
      elective experimental model to compare the signaling of differentiative nerve
      growth factor (NGF) and mitogenic epidermal growth factor (EGF). Focusing on Shc
      as established regulator of the Ras-ERK cascade, whose sustained activation is
      known to critically shape the neuronal differentiation of PC12 cells, the present
      manuscript describes two novel sources of divergence in the signaling of NGF and
      EGF: a differential phosphorylation of p66-Shc at early time points and a
      differential duration in the recruitment of the overall pool of Shc.

PMID- 12802198
TI  - Homotopic glial regulation of striatal projection neuron differentiation.
AB  - We have studied the differentiation of striatal projection neurons in co-culture
      with expanded glia from different regions of the embryonic mouse telencephalon.
      Our results show that when striatal progenitors are cultured on glia derived from
      the same region as they originate (i.e. the lateral ganglionic eminence), the
      neurons formed exhibit long processes. This is not the case when the cells are co
      cultured with glia derived from the adjacent telencephalic region, the medial
      ganglionic eminence. Moreover, expression of the striatal projection neuron
      marker, dopamine- and cAMP-regulated phosphoprotein (DARPP-32) was significantly
      enhanced in neurons cultured on the homotopic glia. Thus, glial cultures derived
      from the lateral ganglionic eminence positively regulate the differentiation of
      striatal projection neurons in vitro.

PMID- 12802199
TI  - Interhemispheric relationships in 4- to 14-year-old children pointing to lateral
      targets.
AB  - Some developmental changes in movement control are not monotonic during
      childhood, which leads us to question how hemispheric relationships develop since
      they are closely involved with visuo-manual coordination. We tested right-handed
      children between 4 and 14 years of age performing pointing movements with the
      right and left hand towards visual targets located in the right and left
      hemifield. The analysis of movement parameters showed a left hand advantage in
      reaction time, but this is mainly due to the contralateral movements relative to
      the semifield of target presentation, suggesting that hemispheric asymmetry is
      not achieved even in older children. Interhemispheric transfer was evaluated
      through the difference between crossed (opposite hand and hemifield side) and
      uncrossed (same hand and hemifield side) movements. The difference was
      significant at all ages, and decreased with age between 4-6 and 7-9 years. It
      moved from early asymmetry in favor of the left-to-right interhemispheric
      transfer to adult-like symmetry at 10-14 years. The long development of
      hemispheric specificity and interhemispheric communication suggested by our
      results might be associated to asynchronous development of various processes
      involved in visuo-motor coordination, leading to qualitative changes in visually
      directed movement during childhood described in the literature.

PMID- 12802200
TI  - Correlations, feature-binding and population coding in primary visual cortex.
AB  - To test the hypothesis that correlated neuronal activity serves as the neuronal
      code for visual feature binding, we applied information theory techniques to
      multiunit activity recorded from pairs of V1 recording sites in anaesthetised
      cats while presenting either single or separate bar stimuli. We quantified the
      roles of firing rates of individual channels and of cross-correlations between
      recording sites in encoding of visual information. Between 89 and 96% of the
      information was carried by firing rates; correlations contributed 4-11% extra
      information. The distribution across the population of either correlation
      strength or correlation information did not co-vary systematically with changes
      in perception predicted by Gestalt psychology. These results suggest that firing
      rates, rather than correlations, are the main element of the population code for
      feature binding in primary visual cortex.

PMID- 12802201
TI  - Assessing disease onset and progression in the SOD1 mouse model of ALS.
AB  - SOD1 transgenic mice are the most widely used animal model of amyotrophic lateral
      sclerosis (ALS). In addition to providing valuable insights into the pathogenesis
      of ALS, these animals are used intensively in many laboratories as an in vivo
      model for investigating novel therapeutic interventions towards this devastating
      motorneuron disease. Such pre-clinical studies require objective and reliable
      quantification of the clinical phenotype of individual mice, most importantly of
      the neuromuscular abnormalities. Here we compare four parameters of the clinical
      phenotype: motor signs, body weight, rotarod performance and paw grip endurance
      for their usefulness in monitoring the SOD1 mouse model. We found that paw grip
      endurance is a sensitive and inexpensive alternative to the widely used rotarod
      test.

PMID- 12802202
TI  - Identification of genes showing differential expression in anorexia mutant mouse.
AB  - Differential display (DD) PCR was applied to identify genes regulated by anorexia
      (anx) in mouse brain. Of the four apparently differentially expressed genes,
      three (H2-H4) had high homology with known genes such as apoptotic protease
      activating factor 1 (Apaf 1), adenylate cyclase 6 (Adcy 6), and myelin
      proteolipid protein (PLP). H1, designated as HIPA1, had a homology with unknown
      function gene fragments. Northern blot analysis confirmed HIPA1 expression
      induced by anorexia. A 1579 bp full-length cDNA of HIPA1 was isolated from a
      mouse brain cDNA library using a probe from the differentially displayed H1
      fragment. Sequence analysis showed that HIPA1 had 98.7% homology to mouse
      hippocampus cDNA. In situ hybridization demonstrated that the HIPA1 mRNA was
      highly up-regulated in the hippocampus of anx/anx mouse brain.

PMID- 12802203
TI  - Vanilloid receptor TRPV1 is not activated by vanilloids applied intracellularly.
AB  - The vanilloid receptor TRPV1 is a ligand-gated cation channel that can be
      activated by capsaicin, acids and noxious heat. For vanilloids, a stretch of
      approximately 8 amino acids in the vicinity of the TM3 region on the cytosolic
      side of TRPV1 and R114 and E761 in the N- and C-cytosolic tails, respectively,
      has been shown to be critical for capsaicin binding and channel activation. Here,
      we report that intracellular application of vanilloids is insufficient for
      activating TRPV1 channels in HEK293T cells. Pipette solution (ICS) for recording
      membrane currents was supplemented with 50 microM capsaicin (n=14) or 1 microM
      resiniferatoxin (RTX) (n=39) and the responses induced by extracellular capsaicin
      (1 microM) or RTX (100 nM) were recorded at intervals >50% of that needed for
      diffusion of Lucifer yellow from the pipette to reach maximum fluorescence (n=7).
      We found that all cells with expressed TRPV1 exhibited a similar sensitivity to
      vanilloids irrespective of whether the membrane currents were recorded with
      electrodes filled with ICS containing capsaicin or RTX or only with control ICS.
      We suggest that, in addition to intracellularly located agonist recognition sites
      of TRPV1, there is at least one resides on the extracellular side, which needs to
      be occupied to activate the channel.

PMID- 12802204
TI  - Caffeic acid produces antidepressive- and/or anxiolytic-like effects through
      indirect modulation of the alpha 1A-adrenoceptor system in mice.
AB  - We previously reported that caffeic acid produce antidepressive- and/or
      anxiolytic-like effects in two different types of stress models. It has recently
      been reported that caffeic acid affects the alpha1A-adrenoceptor system. The
      present study examined whether the alpha1A-adrenoceptor system is involved in the
      antidepressive- and/or anxiolytic-like effects of caffeic acid. Caffeic acid
      reduced the duration of immobility and freezing of mice produced by forced
      swimming and conditioned fear stress, respectively. These effects of caffeic acid
      were suppressed by the alpha1- and alpha1A-adrenoceptor antagonists. However,
      caffeic acid did not alter the binding of [3H]prazosin to alpha1A-adrenoceptor in
      mouse cortical membranes. These results suggest that indirect modulation of the
      alpha1A-adrenoceptor system may be involved in the antidepressive- and/or
      anxiolytic-like effects of caffeic acid.

PMID- 12802205
TI  - A new methodology to define the equilibrium value function in the kinetics of
      (in)activation gates.
AB  - A voltage-gated ion channel is fundamental in generation and propagation of
      electrical signals in the excitable membranes. Dynamics of (in)activation gates
      of the ion channel is modeled by first-order kinetics. The equilibrium value
      function is crucial in the kinetics of the (in)activation gates for fitting
      experimental data. We present a new methodology to define the equilibrium value
      function based on the lowest approximation of the cluster variation method and
      the static properties in the molecular field approximation. The methodology
      allows for exploration of the gating dynamics.

PMID- 12802206
TI  - Vestibular compensation: analysis of postural re-arrangement as a control index
      for unilateral vestibular deficit.
AB  - Patients with an acute unilateral vestibular lesion show an impaired balance
      control. The initial presentation is vertigo followed by postural instability;
      but with time, the global balance functions can be completely restored by a
      process called vestibular compensation. The aim of our study was to evaluate
      short and long-term variations of postural parameters in 20 patients affected by
      vestibular neuritis (VN), and to compare these patients to 20 normal individuals
      using computerized static posturography (CSP) along with patient feedback
      throughout the spectral frequency analysis. This analysis showed in patients with
      no residual dizziness a frequency shift of body sway from low to middle
      frequencies as a probable expression of the compensatory strategies used by the
      central nervous system. On the other hand, patients with persistence of postural
      instability did not show any frequency shift. Our results seem to provide an
      early index of a proper occurring compensation so that we can adjust therapeutic
      protocols according to each patient's functional modifications.

PMID- 12802207
TI  - Awareness of action in schizophrenia.
AB  - An abnormal sense of agency is among the most characteristic yet perplexing
      positive symptoms of schizophrenia. Schizophrenics may either attribute the
      consequences of their own actions to the intentions of others (delusions of
      influence), or may perceive themselves as causing events which they do not in
      fact control (megalomania). Previous reports have often described inaccurate
      agency judgements in schizophrenia, but have not identified the disordered neural
      mechanisms or psychological processes underlying these judgements. We report the
      perceived time of a voluntary action and its consequence in eight schizophrenic
      patients and matched controls. The patients showed an unusually strong binding
      effect between actions and consequences. Specifically, the temporal interval
      between action and consequence appeared shorter for patients than for controls.
      Patients may overassociate their actions with subsequent events, experiencing
      their actions as having unusual causal efficacy. Disorders of agency may reflect
      an underlying abnormality in the experience of voluntary action.

PMID- 12802208
TI  - Functional characterisation of nucleoside transport in rat brain endothelial
      cells.
AB  - Multiple nucleoside transport systems exist in the body yet the subtypes
      functional at the blood-brain barrier (BBB) have not been fully investigated. We
      have employed RBE4 immortalised rat brain endothelial cells to functionally
      identify the carrier subtypes involved in nucleoside transfer between blood and
      brain. Uptake in RBE4 cells was partially sodium dependent, indicating the
      presence of both equilibrative and concentrative systems. Uptake of adenosine via
      equilibrative transporters was sensitive to nitro-benzylmercaptopurine riboside,
      which showed biphasic inhibition. Uptake of [3H]-adenosine via concentrative
      transporters was studied using the subtype-specific inhibitors thymidine (cit),
      formycin-B (cif) and tubercidin (cib) and was significantly reduced by thymidine
      and formycin-B but not by tubercidin. This study suggests that nucleoside
      transport at the in situ BBB may be mediated by ei and es equilibrative
      transporters and by cit and cif concentrative transporters.

PMID- 12802209
TI  - Triptolide inhibits TNF-alpha, IL-1 beta and NO production in primary microglial
      cultures.
AB  - Microglia are believed to participate in the mediation of neurodegeneration
      through producing a variety of cytotoxic factors upon activation. Pharmacological
      intervention in microglial activation may therefore exert a neuroprotective
      effect. In exploring pharmacological agents that can affect microglial
      activation, we found in this study that triptolide possesses a powerful
      inhibitory influence over microglia. Pretreatment with triptolide was able to
      dose-dependently reduce the lipopolysaccharide (LPS)-induced nitrite accumulation
      and tumor necrosis factor-alpha and interleukin-1beta release from LPS-activated
      microglia as revealed by Griess reaction and ELISA, respectively. Triptolide
      reduced LPS-stimulated mRNA expression of all three inflammatory factors. The
      results obtained from this study demonstrate that triptolide can inhibit
      inflammatory responses of microglia to inflammatory stimulation via a mechanism
      involving the inhibition of the synthesis and release of inflammatory factors.

PMID- 12802210
TI  - ACOEM evidence-based statement: noise-induced hearing loss.

PMID- 12802211
TI  - ELISA measurement of stachylysin in serum to quantify human exposures to the
      indoor mold Stachybotrys chartarum.
AB  - The goal of this research was to develop a measurable indicator of human exposure
      to Stachyborys chartarum. Antibodies were produced against the hemolytic agent
      stachylysin obtained from the mold S. chartarum. These antibodies were used to
      develop two enzyme-linked immunosorbent assay methods for the analysis of
      stachylysin in human and rat sera and environmental samples. Stachylysin was
      measured in rat pups that received nasal instillations of S. chartarum conidia
      but not in control rat serum. Stachylysin in the serum of five human adults
      exposed to S. chartarum in water-damaged environments was 371 ng/mL but none was
      detected in the control serum. Stachylysin was also quantified in spore,
      wallboard, mycelial, and dust samples. The measurement of stachylysin may be a
      useful indicator in assessing human exposure to S. chartarum and in determining
      the presence of this indoor mold.

PMID- 12802212
TI  - Assessment of the scientific basis for genetic testing of railroad workers with
      carpal tunnel syndrome.
AB  - In 2000, approximately 20 railroad track workers who filed injury reports or
      compensation claims for carpal tunnel syndrome were tested by their employer for
      two genetic traits to determine the work relatedness of the condition. The
      testing involved deletions, variants, or mutations in the genetic coding for
      peripheral myelin protein (PMP22) and transthyretin (TTR). This article is an
      assessment of whether there is a scientific basis for such testing. A review of
      the scientific literature indicated that neither the scientific basis nor the
      population validity of the PMP22 or TTR tests for carpal tunnel syndrome were
      adequately established before use on railroad track workers in 2000. Although
      ethical and legal issues may predominate in this case, the absence of a
      compelling scientific basis undermines the decision to conduct the tests.

PMID- 12802214
TI  - Pharmaceuticals and worker productivity loss: a critical review of the
      literature.
AB  - Many chronic illnesses that affect the working population can cause losses in
      productivity. The extent to which these productivity losses can be reduced by
      pharmacological treatment is of particular interest to employers, who bear the
      productivity costs and subsidize the cost of employees' health care. In the past
      several years, the effects of pharmaceuticals on productivity losses have been
      tested in numerous studies, including randomized, double-blind, placebo
      controlled trials. In this article, we summarize and critically review these
      studies and, where appropriate, provide quantitative overviews. The evidence is
      very good for about a dozen drug classes that pharmaceuticals reduce productivity
      losses caused by respiratory illnesses (ie, asthma, allergic disorders,
      bronchitis, upper respiratory infections, and influenza) diabetes, depression,
      dysmenorrhea, and migraine. We also discuss the calculation of productivity
      costs, reductions in which may partially or completely offset the costs of
      treatment. This information should be helpful to occupational physicians who are
      increasingly providing recommendations on employer benefit plan designs and
      pharmaceutical benefits.

PMID- 12802213
TI  - Association between dioxins/furans exposures and incinerator workers' hepatic
      function and blood lipids.
AB  - This study examined the effects of dioxins/furans on blood lipids and hepatic
      function and assessed potential interaction between hepatitis B virus (HBV)
      infection and dioxins on hepatic function for 133 male workers of municipal waste
      incinerators. We found that total cholesterol levels in workers with blood
      dioxins/furans levels of 15.4-59.0 pg TEQ/g lipid (high-exposure workers)
      averaged 13.5 mg/dL higher than workers with 5.5-15.3 pg TEQ/g lipid (low
      exposure workers). The adjusted odds ratio for total cholesterol abnormality
      (>220 mg/dL) was 2.8 (95% confidence interval = 1.0-7.9) between high and low
      exposure workers. High-exposure workers showed consistently, although not
      statistically significantly, higher abnormality in gamma-glutamyltransferase (>52
      U/L), alanine aminotransferase (>41 U/L), and aspartate aminotransferase (>37
      U/L) than did low-exposure workers. However, there was no statistically
      significant interaction between dioxins/furans and HBV on these hepatic enzymes
      among incinerator workers.

PMID- 12802215
TI  - Association between exposure to workplace secondhand smoke and reported
      respiratory and sensory symptoms: cross-sectional study.
AB  - The purpose of this work was to assess the relation between exposure to
      secondhand smoke (SHS) at work and reported respiratory and sensory symptoms. A
      cross-sectional telephone survey of 382 nonsmoking indoor workers in Victoria,
      Australia was used. After controlling for potential confounders, exposure to SHS
      at work for part of the day was significantly associated with an increased risk
      of wheeze (OR = 4.26), frequent cough (OR = 2.26), sore eyes (OR = 3.77), and
      sore throat (OR = 2.70). Among workers who had not experienced a cold in the past
      4 weeks, we found strong dose-response relationships between increasing levels of
      exposure to SHS at work and morning cough, frequent cough, sore eyes and sore
      throat, and a positive relationship for wheeze. These findings provide compelling
      evidence that nonsmoking indoor workers are adversely affected by exposure to SHS
      at work and underline the importance of workplace smoke-free policies in
      protecting the health of workers.

PMID- 12802216
TI  - Occupational differences in levels of anxiety and depression: the Hordaland
      Health Study.
AB  - The literature on anxiety and depression in work life is scarce. This study
      examined if and how levels of anxiety and depression differed between
      occupations. The study encompassed 17384 workers with occupations classified
      according to ISCO-88 (COM) from the population-based Hordaland Health Study.
      Levels of anxiety and depression were assessed by the anxiety and depression
      subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D,
      respectively). Main analytical method was univariate analysis of variance. Both
      HADS-A and HADS-D scores differed significantly between occupaional groups. HADS
      levels showed a distinct and inverse association with skill levels, most strongly
      observed for HADS-D scores in men. The relationship between skill levels and
      depression caseness was equally strong. Elementary occupations consistently
      showed higher-than-average HADS scores. The strength of the associations between
      depression score/caseness and skill levels are of clinical significance.
      Screening for depression should be considered in low-skill occupations.

PMID- 12802217
TI  - Occupation and adult gliomas in the San Francisco Bay Area.
AB  - The etiology of gliomas is not well understood. Some jobs might involve sustained
      and elevated exposures to carcinogens. This study compares lifetime job histories
      of 879 glioma cases diagnosed between August 1991 to April 1994 and May 1997 to
      August 1999 in the San Francisco Bay Area and 864 controls. Logistic analyses
      compared longest and ever held occupations of 1 year or more for all astrocytic
      and nonastrocytic cases and controls overall with adjustment for age, gender, and
      ethnicity and separately for men and women. Two-fold or higher or statistically
      significant elevated odds ratios were found overall and in men among those with
      longest held occupations, as firefighters, physicians, material moving equipment
      operators, and janitors; such elevated odds ratios were also observed for longest
      held occupations among male motor vehicle operators and personal service workers
      and female messengers, legal/social service workers, electronic equipment
      operators, painters, and food processors. Odds ratios of 0.50 or less, but not
      statistically significant, were found for those with longest held jobs as
      writers/journalists, biological scientists, paper workers, mechanics, chemists,
      and photographers/photoprocessors. This study supports previously observed
      occupational associations and is one of the few studies with sufficient numbers
      to separately analyze occupations by gender.

PMID- 12802218
TI  - Allergic sensitization, symptoms, and lung function among bakery workers as
      compared with a nonexposed work population.
AB  - Only few studies have assessed relative risks on occupational asthma and allergy
      among bakery workers, and none of them have included respiratory and work-related
      symptoms as well as sensitization to occupational allergens and pulmonary
      function. A random sample of 246 workers from traditional and industrial bakeries
      in two regions of Belgium were compared with a reference population of 251
      workers from a petrochemical plant in the same region. Data on skin test
      positivity, symptoms, and lung function were collected by standardized
      procedures. Differences between the two subpopulations were analyzed using
      multiple logistic and linear regression analyses. On average, bakery workers did
      not more often have skin test positivity than reference workers (39.4% and 42.6%,
      respectively). However, bakery workers had a strongly increased risk of
      sensitization to specific bakery allergens (OR 22.0, 95% CI = 6.3-77.1.), whereas
      their risks of positive skin tests to common allergens, including wheat pollen
      and storage mite, were significantly decreased (OR 0.6, 95% CI = 0.4-0.9). Bakery
      workers had significantly more often respiratory and work-related symptoms.
      Accordingly, they had lower lung function parameters. Atopy and sensitization to
      bakers' allergens were independent and additional risk factors for work-related
      symptoms. Bakery workers are at increased risk of respiratory and allergic
      symptoms and skin test reactivity to specific bakers' allergens wheat flour and
      alpha-amylase. Wheat pollen and storage mite should not be regarded as baker's
      allergens. Nevertheless, pulmonary function of bakery workers can be
      characterized as mild airway obstruction only.

PMID- 12802219
TI  - Shade tobacco and green tobacco sickness in Connecticut.
AB  - The prevalence of Green Tobacco Sickness (GTS) among shade tobacco farmworkers in
      Connecticut is unknown. We conducted a study to determine the prevalence of GTS
      in farmworkers working in shade tobacco fields who presented for clinical care at
      medical student-run clinics. A retrospective chart review of the tobacco workers
      seen at Farmworkers' Clinics during 2001 was instituted in this study. Although
      GTS was not clinically diagnosed in any of the patients, we found 15% diagnoses
      that could be attributed to possible GTS by ICD-9 code review. Using a stricter
      GTS case definition, the frequency rate decreased to 4%. Nonsmokers were
      significantly more likely than smokers to report GTS-like symptoms (P < 0.01).
      Isolated symptoms of headache and dizziness were significantly more frequent
      among nonsmokers than smokers (P < 0.05). In conclusion, cases of possible GTS
      were found in Connecticut shade tobacco workers. Nonsmokers were more at risk to
      have possible GTS than smokers.

PMID- 12802220
TI  - Gender as a moderator of memory after traumatic brain injury in children.
AB  - OBJECTIVE: To explore the possibility that gender has a moderating effect on
      memory after pediatric traumatic brain injury (TBI). DESIGN: Controlled group
      study. Gender effects between and within groups were evaluated by means of effect
      size comparisons and hierarchical regression analysis. SETTING: Regional
      rehabilitation center. PARTICIPANTS: Seventy children with TBI, selected from a 4
      year series of consecutive referrals, and 70 demographically matched controls.
      MAIN OUTCOME MEASURES: Screening version of the Wide Range Assessment of Memory
      and Learning (WRAML-S) and the Wechsler Intelligence Scale for Children-Third
      Edition (WISC-III). RESULTS: Boys with TBI performed worse than girls with TBI,
      and worse than their counterparts in the control group, on the WRAML-S. There was
      no gender effect in the control group. Gender explained an additional 9% of the
      variance in WRAML-S performance over and above injury severity and age variables.
      However, gender differences were largely attenuated when speed of information
      processing, as assessed by the WISC-III, was used as a covariate. CONCLUSION: The
      effect of TBI on children's memory appears to be moderated by gender and may be
      mediated by speed of information processing.

PMID- 12802221
TI  - Rural versus urban social support seeking as a moderating variable in traumatic
      brain injury outcome.
AB  - OBJECTIVE: To investigate personal beliefs about seeking social support following
      traumatic brain injury (TBI) and the relationship of these appraisals to
      demographic and injury variables, social integration, and quality of life
      ratings. SETTING: The central region of a Midwest state. PARTICIPANTS: Fifty-six
      adults with TBI who were more than 6 months postinjury and living in the
      community. MAIN OUTCOME MEASURES: The Hesitation Scale, a 20-item survey that
      assesses reasons that people might hesitate to reach out to others in the
      community, and portions of the Living Life After Traumatic Brain Injury Scale.
      RESULTS: Negative attitudes and beliefs about seeking social support were
      significantly related to lower perceptions of social support, lower ratings of
      quality of life, longer time since injury, being divorced or separated, and
      living in an urban area. Predictors of higher quality of life ratings included
      more positive appraisals about seeking social support, living in a rural area,
      and the ability to engage in productive activity. CONCLUSIONS: Positive outcomes
      after TBI appear to be moderated by living in a rural area, which is associated
      with more openness to seeking social supports and contributes to better quality
      of life.

PMID- 12802222
TI  - Moderating factors in return to work and job stability after traumatic brain
      injury.
AB  - OBJECTIVE: To examine job stability moderating variables and develop a postinjury
      work stability prediction model. DESIGN: Multicenter analysis of individuals with
      traumatic brain injury (TBI) who returned for follow-up at 1, 2, and 3, or 4
      years postinjury, were of working age (between 18 and 62 years of age at injury),
      and were working preinjury. SETTING: Six National Institute on Disability and
      Rehabilitation Research TBI Model System centers for coordinated acute and
      rehabilitation care. PARTICIPANTS: A total of 186 adults with TBI were included
      in the study. MAIN OUTCOME MEASURES: Job stability was categorized as stably
      employed (employed at all 3 follow-up intervals); unstably employed (employed at
      one or two of all three follow-up intervals); and unemployed (unemployed at all
      three follow-up intervals). RESULTS: After injury, 34% were stably employed, 27%
      were unstably employed, and 39% were unemployed at all three follow-up intervals.
      Minority group members, people who did not complete high school, and unmarried
      people were more likely to be unemployed. Driving independence was highly
      influential and significantly related to employment stability. A discriminant
      function analysis, which included age, length of unconsciousness and Disability
      Rating Scale scores at 1 year postinjury, accurately predicted job stability
      groupings. CONCLUSION: Data analysis provided evidence that employment stability
      is predictable with a combination of functional, demographic, and injury severity
      variables. Identification of people at risk for poor employment outcomes early on
      can facilitate rehabilitation planning and intervention.

PMID- 12802223
TI  - A longitudinal study of compensation-seeking and return to work in a treated mild
      traumatic brain injury sample.
AB  - OBJECTIVE: In patients with mild traumatic brain injury (MTBI), to assess: (1)
      changes in financial compensation-seeking status over time and (2) the
      relationship between compensation-seeking and return to work. DESIGN:
      Longitudinal evaluation of financial compensation-seeking status (i.e., at
      intake, 3 months postinjury, and 12 months postinjury) and relationship of such
      status to return to work. SETTING: Outpatient rehabilitation clinic. SUBJECTS:
      Ninety-seven patients with MTBI. MAIN OUTCOME MEASURES: Compensation-seeking
      status at 3 and 12 months and days taken to return to preinjury vocational
      activity. RESULTS: Those in litigation at intake generally continued to be in
      litigation at 3 and 12 months postinjury. Those seeking or receiving compensation
      via administrative means (e.g., sick pay or workers' compensation) at intake were
      generally not seeking or receiving compensation by 3 months or later, as was the
      case for most of those not seeking any financial compensation at intake. Patients
      seeking or receiving financial compensation via litigation and/or administrative
      means at intake took longer to return to work than did people who were not
      seeking or receiving compensation at intake. CONCLUSION: The present study design
      does not allow for determination of the reasons for the strong relationship
      between financial compensation-seeking soon post-MTBI and a slow return to work.
      However, the strength of the present findings indicates that the presence or
      absence of financial compensation-seeking soon post-MTBI should be routinely
      evaluated when return to work is an issue.

PMID- 12802224
TI  - Demographic, medical, and psychiatric factors in work and marital status after
      mild head injury.
AB  - OBJECTIVE: To explore factors associated with long-term outcomes of work and
      marital status in individuals who had experienced a mild head injury (MHI), as
      well as those who had not. DESIGN: Population-based study using logistical
      regression analyses to investigate the impact of preinjury characteristics on
      work and marital status. PARTICIPANTS: Two groups of Vietnam-era Army veterans:
      626 who had experienced a MHI an average of 8 years before examination, and 3,896
      who had not. MAIN OUTCOME MEASURES: Demographic characteristics, concurrent
      medical conditions, early life psychiatric problems, loss of consciousness (LOC),
      and interactions among these variables were used to predict current work and
      marital status. RESULTS: Multiple variables were associated with work and marital
      status in the sample with MHI, accounting for approximately 23% and 17% of the
      variance in these two outcome variables, respectively. In contrast, the same
      factors accounted for significantly less variance in outcome in the sample
      without a head injury-13.3% and 9.4% for work and marital status, respectively.
      CONCLUSIONS: These findings suggest a more potent role for and increased
      vulnerability to the influence of demographic, medical, and psychiatric factors
      on outcomes after a MHI. That is, MHI itself moderates the influence of preinjury
      characteristics on work and marital status. In addition, in those who had a MHI,
      moderator relationships were found between education and LOC for both work and
      marital status. Similarly, complex moderator relationships among race, region of
      residence, and LOC were found for both work and marital status outcomes.

PMID- 12802225
TI  - Parent-adolescent interactions after traumatic brain injury: their relationship
      to family adaptation and adolescent adjustment.
AB  - OBJECTIVE: To examine changes in parent-adolescent interactions after traumatic
      brain injury (TBI) and their relationship to parent and adolescent adjustment.
      DESIGN: Concurrent cohort, cross-sectional study. Analysis of variance was used
      to examine group differences and regression analysis to assess associations
      between interactional measures and concurrent adjustment. SETTING: Four hospitals
      in north-central Ohio. PARTICIPANTS: Adolescents with severe TBI (25), moderate
      TBI (22), and orthopedic injuries (35) and their parents. MAIN OUTCOME MEASURES:
      Observer ratings of parent-adolescent interactions, Conflict Behavior
      Questionnaire (CBQ), Family Burden of Injury Interview (FBII), Brief Symptom
      Inventory (BSI), Family Assessment Device (FAD), Child Behavior Checklist,
      Vineland Adaptive Behavior Scale, and Children's Depression Inventory. RESULTS:
      No group differences were found on ratings of parent-adolescent interaction or
      the parent or child CBQ. However, observed criticism/coldness and self-rated
      conflict had stronger associations with the FBII, BSI, and FAD in the severe TBI
      group than in the orthopedic injury group, suggesting that conflict is more
      disruptive after TBI. Ratings of criticism/coldness and parent and adolescent CBQ
      scores were also associated with parent and adolescent adjustment. CONCLUSIONS:
      Results support the utility of observational measures in assessing dyadic
      interactions after TBI.

PMID- 12802226
TI  - The use of atypical antipsychotics in traumatic brain injury.
AB  - The use of antipsychotic medication in treating individuals with traumatic brain
      injury (TBI) has been controversial. Much of the caution derives from animal
      studies (and limited human data) with regard to typical antipsychotics. Of note,
      however, is that similar assumptions have been made about the newer generation of
      atypical antipsychotics as well. Because these agents have different mechanisms
      of action as well as different neurotransmitter targets, this may very well be
      unwarranted. In this article, mechanisms of action of typical and atypical
      antipsychotics are discussed, with particular attention paid to their use in TBI.
      Indications and contraindications are presented, and recommendations are made for
      the responsible prescribing of antipsychotic medications after TBI.

PMID- 12802227
TI  - Ginseng.

PMID- 12802229
TI  - A campaign for a "cure".

PMID- 12802228
TI  - Traumatic brain injury: depression, neurogenesis, and medication management.

PMID- 12802235
TI  - Positive supports for people who experience behavioral and cognitive disability
      after brain injury: a review.
AB  - BACKGROUND: Behavioral and cognitive problems are among the most common and
      troubling consequences of traumatic brain injury. Furthermore, behavioral and
      cognitive challenges typically interact in complex ways, necessitating an
      integrated approach to intervention and support. OBJECTIVES: This article reviews
      literature on behavioral outcome in children and adults with traumatic brain
      injury, traditional approaches to behavioral intervention and cognitive
      rehabilitation, and the history, principles, and assessment and treatment
      procedures associated with context-sensitive, support-oriented approaches to
      behavioral and cognitive intervention. We propose a clinical framework that
      integrates cognitive and behavioral intervention themes.

PMID- 12802236
TI  - Context-sensitive behavioral supports for young children with TBI: short-term
      effects and long-term outcome.
AB  - OBJECTIVE: To investigate the effects of a multicomponent cognitive-behavioral
      intervention on the challenging behavior of two young children with growing
      behavioral concerns after traumatic brain injury. DESIGN: Single-subject reversal
      designs were used to document the effects of the intervention on the specific
      dependent variables. In addition, qualitative data were collected to determine
      the children's long-term outcome and staff evaluations of the intervention.
      PARTICIPANTS: Both children were normally developing before injury at age 5
      years. Both experienced increasing behavior problems as expectations in school
      escalated. MAIN OUTCOME MEASURES: Quantitative data included frequency and
      intensity of aggression and amount of work completed. Qualitative data included
      children's general engagement in school work and peer interaction and staff
      evaluations of the intervention. INTERVENTION: The intervention included
      components of positive behavior supports, cognitive supports, and an executive
      function routine. RESULTS: The targeted challenging behaviors were reduced to
      near zero with decreased intensity. Long-term outcome was positive. CONCLUSIONS:
      These results illustrate the potential for successfully treating behavior
      disorders in young children with traumatic brain injury using a support-oriented
      intervention that combines behavioral and cognitive components.

PMID- 12802238
TI  - The safe management of physical aggression using multi-element positive practices
      in community settings.
AB  - BACKGROUND: Behavioral strategies often are used with people with acquired brain
      injury. Most involve the application of contingent reinforcement and punishment
      for selected behaviors or teaching important skills to overcome the challenging
      behaviors. However, consequential intervention and other strategies that depend
      on new learning may be precluded when working with individuals with significant
      short-term memory impairment. MAIN OUTCOME MEASURES: The present case study
      reports the results of non-consequential strategies based on a positive, multi
      element model to address physical aggression and other related problems for such
      an individual. RESULTS: Support did not involve the use of aversive consequences
      for challenging behaviors nor the use of physical management/restraint. The
      identified problems were effectively and safely addressed and community living in
      close proximity to his family was maintained. CONCLUSIONS: The implications of
      this approach for the support of people who face similar challenges are
      discussed, including the ability to address serious problems such as physical
      aggression without resorting to aversive procedures.

PMID- 12802237
TI  - Intensive positive behavior supports for adolescents with acquired brain injury:
      long-term outcomes in community settings.
AB  - BACKGROUND: Based on the technologies of applied behavior analysis and person
      centered planning, positive behavior support is a process for designing and
      implementing proactive behavioral interventions with the goal of positive
      lifestyle changes. PARTICIPANTS: The two adolescents who received the intensive,
      longitudinal, multicomponent intervention had experienced escalating behavior
      challenges over several years after brain injury in early childhood. MAIN OUTCOME
      MEASURES: Quantitative data included episodes of aggression and property
      destruction. Qualitative data included intensity of supports, family involvement,
      peer relationships, medication regime, vocational status, educational status,
      community access, and self-help skills. RESEARCH DESIGN: A long-term, natural
      environment, case-study method was used. RESULTS: The targeted challenging
      behaviors were reduced to zero. In addition, the participants' domains of
      activity increased and self-management improved even as supports were
      systematically withdrawn. CONCLUSIONS: These results illustrate the potential for
      successfully treating extreme chronic behavior disorders after childhood brain
      injury.

PMID- 12802239
TI  - "Errorless" rehabilitation: strategies of proactive intervention for individuals
      with brain injury and their children.
AB  - BACKGROUND: Individuals with brain injury are prone to severe behavior problems
      related to various postinjury variables, including confusion, emotional distress,
      fear of challenging activity, and loss of skills to access desired outcomes.
      OBJECTIVES: This article proposes the use of a new model, errorless
      rehabilitation, to improve rehabilitation outcomes by systematically focusing on
      graduated and success-based exposure of clients with brain injury to increasingly
      demanding circumstances, to provide them with the ability to tolerate and manage
      the natural environment. MAIN OUTCOME MEASURES: Research on difficulties parents
      with brain injury experience with their children is subsequently reviewed and a
      new approach (based on the same principles as Errorless Rehabilitation) to
      treatment of parent-child relationship issues after brain injury is described.
      CONCLUSIONS: A case study of a father with brain injury and his oppositional son
      is presented to demonstrate a specific application of this model for enhancing
      the quality of life of parents with such impairments.

PMID- 12802240
TI  - Blunt versus penetrating violent traumatic brain injury: frequency and factors
      associated with secondary conditions and complications.
AB  - OBJECTIVE: To compare types and frequency of medical complications and
      comorbidities associated with violence-related penetrating traumatic brain injury
      (TBI) as compared to violence-related blunt TBI. METHOD: Data were collected
      prospectively at four medical centers participating in the TBI Model Systems
      (TBIMS) of Care project. A total of 317 individuals met the inclusion criteria
      for the TBIMS (i.e., showed evidence of a TBI, were age 16 or older, presented to
      the TBIMS emergency department within 24 hours of injury, and received acute and
      rehabilitation services within the model system). MAIN OUTCOME MEASURES:
      Frequency of medical complications and comorbid diseases. RESULTS: Patients with
      penetrating injuries suffered significantly higher rates of respiratory failure
      (P =.004), pneumonitis/pneumonia, (P =.002), skull fracture (P =.001),
      cerebrospinal fluid leak (P =.0005), and hypotonia (P =.001) than did patients
      with blunt injuries. Prediction of complications and comorbidities via multiple
      regression revealed that a penetrating violent injury and the severity of injury
      were independent predictors of a higher rate of medical complications, whereas
      age and gender did not account for unique variance in the equation. CONCLUSIONS:
      Penetrating injuries are associated with higher rates of certain medical
      complications, especially to the pulmonary and central nervous systems. Acute
      care physicians and physiatrists must be prepared to treat these complications
      more often in patients with penetrating injuries.

PMID- 12802241
TI  - Comparison of the Community Integration Questionnaire, the Craig Handicap
      Assessment and Reporting Technique, and the Disability Rating Scale in traumatic
      brain injury.
AB  - OBJECTIVE: To examine the concurrent validity of the Community Integration
      Questionnaire (CIQ) in assessing outcomes in traumatic brain injury (TBI) by
      comparing it with two widely used and well-validated measurements of
      rehabilitation outcome. DESIGN: A retrospective relational study of the
      concurrent validity of the CIQ, Craig Handicap Assessment and Reporting Technique
      (CHART), and Disability Rating Scale (DRS). SETTING: A postacute rehabilitation
      facility. PARTICIPANTS: Seventy patients with a medical diagnosis of TBI admitted
      between April 1996 and October 1998 participated in the study. RESULTS: CIQ and
      CHART provide ratings that are similar in several areas to those provided by the
      DRS. Correlation (r) among total scores and subscales for all three instruments
      ranged from 0.021 to 0.671 (P <.01). Correlation between CIQ and CHART is
      stronger than that between CIQ and DRS or between CHART and DRS, and the
      correlation between CHART and DRS is stronger than that between CIQ and DRS.
      CONCLUSION: The CIQ appears to be the most appropriate instrument in quantifying
      rehabilitation outcome in patients with TBI at the participatory (handicap)
      level. The findings of this study can help clinicians gain a greater
      understanding of the nature, redundancy, and gaps among functional outcome
      measures. Monitoring outcomes can also help clinicians better understand the
      effectiveness of interventions.

PMID- 12802242
TI  - Retrospective assessment of rehabilitation outcome after traumatic brain injury:
      development and utility of the functional independence level.
AB  - OBJECTIVE: To develop a measure suitable for retrospective analysis of
      qualitative brain injury outcome data, the Functional Independence Level (FIL),
      and document its reliability, validity, and utility. DESIGN: Retrospective
      analysis of existing records, with inclusion based on availability of records,
      and quantitative or qualitative documentation of functional status at a minimum
      of 1.5 years after injury. SETTING: Statewide acute and postacute rehabilitation
      facilities, as part of a State Head Injury Program. PARTICIPANTS: A total of 338
      individuals, with documented moderate to severe traumatic brain injury; primarily
      males ages 16 to 45. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) at
      discharge from primary rehabilitation, Living Situation and Functional
      Independence Level coded from information in postacute rehabilitation reports, at
      an average of approximately 6 years after injury. RESULTS: Inter-rater
      reliability coefficients for FIL ratings extracted from rehabilitation records,
      and between retrospective and in vivo assessments were highly significant. DRS
      scores at discharge from primary rehabilitation predicted a significant amount of
      variance in FIL scores at an average of 5 years after injury, and DRS scores
      remained a stable and significant predictor of FIL scores as the time period
      between discharge from rehabilitation and outcome ratings increased to 10 years
      after injury. FIL ratings were significantly lower for individuals living in
      residential facilities than those living with their families, as compared to
      living alone. CONCLUSIONS: The FIL is a reliable and useful tool for
      retrospective and prospective assessments of rehabilitation outcome. Gains made
      during primary rehabilitation by people with severe traumatic brain injury are
      generally maintained at long-term follow up. Retrospective ratings using the DRS
      and FIL can help guide postacute rehabilitation planning within state or regional
      head injury programs.

PMID- 12802243
TI  - Early cognitive and affective sequelae of traumatic brain injury: a study using
      the BNI Screen for Higher Cerebral Functions.
AB  - OBJECTIVE: To demonstrate that the Barrow Neurological Institute (BNI) Screen for
      Higher Cerebral Functions (BNIS) can be used to briefly assess cognitive and
      affective disturbances during the acute stages after traumatic brain injury
      (TBI). DESIGN AND OUTCOME MEASURES: People with TBI were administered the BNIS
      during the first 60 days after injury and their performance compared to a
      convenience sample of control subjects used in the standardization of the BNIS.
      SETTING: Inpatient units of a neurological institute and medical center.
      SUBJECTS: Forty-two individuals with moderate-to-severe TBI and 21 control
      subjects. RESULTS: Compared to patients with TBI, control subjects performed
      significantly better on the BNIS total and all subtest scores. TBI patients were
      best classified by poor performance on measures of affect disturbance and
      impaired awareness. Stepwise discriminant analysis identified disturbances in
      memory, awareness, and affect as contributing most to the classification of an
      individual as having TBI. CONCLUSIONS: Both cognitive and affective disturbances
      can be directly assessed during the early stages after significant TBI. The BNIS
      can be used for this purpose and help document that TBI specifically affects
      memory, awareness, and affect during its early stages and should be addressed in
      rehabilitation.

PMID- 12802244
TI  - Telerehabilitation support for families at home caring for individuals in
      prolonged states of reduced consciousness.
AB  - OBJECTIVE: To investigate the use of telerehabilitation to support families
      caring at home for individuals with prolonged states of reduced consciousness.
      DESIGN: A comparison group approach. PARTICIPANTS: Participants were recruited
      from a special program that is part of a Model Systems brain injury program
      located in the Southeast. Five patients, ranging from Rancho 1 to Rancho 3 were
      discharged home with family members as the primary caregivers. PROCEDURES:
      Participant families were followed for 4 to 8 weeks via videophone. Follow-up
      telephone surveys were conducted with a family member 6 to 9 months after
      discharge and compared with a similar group that had not received the videophone
      follow-up. MAIN OUTCOME MEASURES: Present living status, number of emergency room
      visits, number of hospitalizations, the caregivers' perceptions of functional
      status and care needs, readmission for rehabilitation and perceived family needs
      as measured by the Family Needs Questionnaire (FNQ). RESULTS: More patients in
      the videoconferencing group were still living at home and had returned for
      rehabilitation. On the FNQ, families in the videophone group reported more of
      their needs met than families in the comparison group. CONCLUSIONS: The use of
      videoconferencing to bridge the transition to home for families caring for a
      family member at the Rancho 1 to Rancho 3 level may assist families in
      successfully caring for the individual in the home and reducing the number of
      perceived family needs.

PMID- 12802245
TI  - Cognitive rehabilitation: a goal-planning approach.
AB  - BACKGROUND: This case study describes a 33-year-old man who sustained a severe
      head injury with cerebrovascular complications in a road traffic accident.
      METHOD: His rehabilitation program focused on the everyday problems he faced as a
      result of cognitive deficits resulting from his brain injury. Twelve goals were
      set after negotiations between the man, his wife, and the rehabilitation team.
      RESULTS: All goals were achieved by the end of his program. We describe how they
      were achieved and provide data for three goals in particular. We discuss the
      advantages of a goal planning approach in cognitive or neuropsychological
      rehabilitation.

PMID- 12802246
TI  - Use of a portable voice organizer to remember therapy goals in traumatic brain
      injury rehabilitation: a within-subjects trial.
AB  - OBJECTIVE: To test the efficacy of a portable voice organizer in helping people
      with traumatic brain injury (TBI) to recall therapy goals and plans discussed
      with their clinical case managers. DESIGN: Prospective within-subjects trial, in
      which individualized therapy goals were randomly assigned to intervention or no
      intervention. SETTING: Comprehensive postacute TBI rehabilitation program.
      PARTICIPANTS: Ten people with moderate to severe TBI enrolled from 3 months to 18
      years after injury. OUTCOME MEASURE: Memory for therapy goals. Clinicians
      generated statements describing six current therapy goals, half of which were
      randomly assigned to be recorded on a voice organizer during the next case
      management session. Participants selected three times per day to listen to the
      recorded goals, prompted by an alarm. One-week recall was tested using both free-
      and cued-recall formats. RESULTS: Recorded goals were recalled better than
      unrecorded goals and appeared to be associated with better awareness or follow
      through with therapy objectives. CONCLUSION: Portable electronic devices have the
      potential to assist with treatment areas beyond tasks involving prospective
      memory.

PMID- 12802247
TI  - The cytochrome p-450 drug metabolizing enzyme system: an overview of potential
      clinically important drug interactions.

PMID- 12802249
TI  - Neuropsychological technologies in rehabilitation.
AB  - OBJECTIVE: To provide an introduction and a conceptual context for the articles
      presented in this special edition of the Journal of Head Trauma Rehabilitation on
      neuropsychological technologies. SUMMARY: Many clinical assessments in
      neuropsychology are metamorphosing from a psychometric search for a lesion to a
      functional image of the working brain. Behavioral probes increasingly employ
      technology to provide more ecologically valid stimuli to elicit diagnostically
      relevant responses. Intervention strategies include an expanding range of
      assistive devices and technologically based treatments. The advent of the
      microprocessor and discipline specific programming have allowed certain aspects
      of rehabilitation practice to incorporate these new assessment and intervention
      strategies. For example, the development of neuropsychological technologies has
      already lead to computer based prosthetics and orthotics, cognitive probes with
      millisecond accurate links to functional imaging, virtual reality managed
      ecological assessments, cognitive retraining, assistive devices, and online, and
      "real-time" database-driven evaluations. Emerging technologies offer the
      potential for personal, portable, everyday brain imaging and rehabilitation
      systems. Few psychologists, physiatrists, or allied health professionals are
      formally trained in technological development. What has emerged thus far is a
      collection of individual efforts that remain to be integrated into more
      comprehensive tools for the rehabilitation professions. The selective history of
      neuropsychological technologies presented here is meant to illustrate past
      difficulties in the emergence of this sub-specialty and point to new applications
      and technological integration that may prove fruitful. The convergence of
      neuroengineering, adaptive assessments, everyday neuroimaging, neuroinformatics,
      and educational neuroimaging, presage such future developments in
      neuropsychological technologies.

PMID- 12802250
TI  - Virtual reality and neuropsychology: upgrading the current tools.
AB  - BACKGROUND: Virtual reality (VR) is an evolving technology that has been applied
      in various aspects of medicine, including the treatment of phobia disorders, pain
      distraction interventions, surgical training, and medical education. These
      applications have served to demonstrate the various assets offered through the
      use of VR. OBJECTIVE: To provide a background and rationale for the application
      of VR to neuropsychological assessment. METHODS: A brief introduction to VR
      technology and a review of current ongoing neuropsychological research that
      integrates the use of this technology. CONCLUSIONS: VR offers numerous assets
      that may enhance current neuropsychological assessment protocols and address many
      of the limitations faced by our traditional methods.

PMID- 12802251
TI  - Applications of computer-based neuropsychological assessment.
AB  - OBJECTIVES: To present current applications of computer-based neuropsychological
      assessment, including the assessment of sports-related concussion, symptom
      validity testing, and the remote administration of tests through the Internet.
      PROBLEM AREAS: If computer-based assessment benefits are to become popularized, a
      few issues will need to be addressed: the development of psychometric data based
      on comparisons with long-standing empirically sound test measures; additional
      validation of measures by parties not involved in their commercial development;
      increased focus on ecological validity; exploration of the usefulness of remote
      data storage and automated posting to databases; and improved documentation of
      specific computer hardware and software used in experimental methods.
      CONCLUSIONS: Beyond ease of administration and data collection, computer-based
      assessment offers benefits over paper-and-pencil measures in the form of
      millisecond timing accuracy, reliable and randomized presentation of stimuli over
      multiple trials and repeat administrations, and unobtrusive measurement of
      cognitive skills and response times during all aspects of the assessment process.

PMID- 12802252
TI  - Functional magnetic resonance imaging technology and traumatic brain injury
      rehabilitation: guidelines for methodological and conceptual pitfalls.
AB  - OBJECTIVES: To illuminate the current methodological and conceptual pitfalls
      inherent in conducting functional magnetic resonance imaging (fMRI) research with
      individuals who have sustained traumatic brain injury (TBI) and to discuss
      appropriate remedies. The aim is describe fMRI research, its limitations, and how
      to best use this technology to examine TBI. DISCUSSION: The topics discussed in
      this article include issues regarding signal detection, brain activation
      measurement, head movement, and sources of signal artifact. Issues surrounding
      data interpretation and the importance of analyzing the brain as a connected
      neural network is also discussed. Finally, problems with spatial normalization
      when examining individuals with TBI are reviewed. CONCLUSIONS: To date, there is
      a scarcity of research applying fMRI technology to the study of TBI. However,
      because it is a noninvasive procedure with high availability in hospital settings
      across the country, the next decade of TBI research will likely include a
      proliferation of this form of investigation. At this time, much work is needed to
      better understand how to optimally use this technology to examine the effects of
      TBI on behavior. For fMRI to enhance TBI research it will be imperative to
      establish valid research protocols and reliable methods of data interpretation.

PMID- 12802253
TI  - The benefits of a cognitive orthotic in brain injury rehabilitation.
AB  - BACKGROUND: Properly designed software can be compensatory, and possibly
      remedial, for people with significant deficits from traumatic brain injury (TBI).
      OBJECTIVE: This article will provide a historical overview of the use of
      microcomputers in brain injury rehabilitation. Emphasis will be placed on the
      evolution of compensatory assistive technology for overcoming cognitive
      impairments, with theoretical discussion of the design considerations for an
      effective cognitive orthotic. CONCLUSIONS: Discussion will focus on findings and
      observations made with a particular multifunction cognitive orthotic system to
      assist people with TBI in the performance of ecologically relevant activities.
      Additional observations will address the impact of the current US health care
      environment on technological innovation.

PMID- 12802254
TI  - Historical review of computer-assisted cognitive retraining.
AB  - OBJECTIVES: This article details the introduction and development of the use of
      microcomputers as adjuncts to traditional cognitive rehabilitation of persons
      with acquired brain injury. SUMMARY: The initial application of video games as
      therapeutic recreation in the late 1970s was soon followed in the early 1980s by
      the use of the first personal computers and available educational software. By
      the mid-1980s, both the IBM PC and Macintosh platforms were established, along
      with simplified programming languages that allowed individuals without extensive
      technical expertise to develop their own software. Several rehabilitation
      clinicians began to produce and market specially written cognitive retraining
      software for one or the other platform. Their work was detailed and reviewed, as
      was recently released software from commercial sources. The latter discussion
      included the latest developments in the rehabilitation applications of personal
      digital assistants and related organizing, reminding, and dictation devices. A
      summary of research on the general and specific efficacy of computer-assisted
      cognitive retraining illustrated the lingering controversy and skepticism that
      have been associated with this field since its inception. CONCLUSIONS: Computer
      assisted cognitive retraining (CACR) can be an effective adjunct to a
      comprehensive program of cognitive rehabilitation. Training needs to be focused,
      structured, monitored, and as ecologically relevant as possible for optimum
      effect. Transfer or training or generalizability of skills remains a key issue in
      the field and should be considered the key criterion in evaluating whether to
      initiate or continue CACR.

PMID- 12802255
TI  - Development and validation of a web-based screening tool for monitoring cognitive
      status.
AB  - OBJECTIVES: We acquired normative data for an Internet neurocognitive screening
      tool, the Cognitive Stability Index (CSI), and investigated its validity both for
      initial assessment and for detecting significant change. PARTICIPANTS: Normative
      data on a nationally representative sample of 284 individuals aged 18 to 89.
      Validity data was obtained for outpatient groups of mild-to-moderate TBI,
      attention deficit/hyperactivity disorder (AD/HD), and Alzheimer's disease.
      RESULTS: The CSI subtests resolve to four factors: attention, processing speed,
      motor speed, and memory with acceptable psychometric properties. Patterns of
      scores obtained by three groups of patient-participants provided reasonable
      evidence of clinical validity for screening and monitoring change. CONCLUSIONS:
      An Internet-based system holds promise for applying complex statistical models
      for routine monitoring of cognitive function.

PMID- 12802256
TI  - Educational neuroimaging: a proposed neuropsychological application of near
      infrared spectroscopy (nIRS).
AB  - OBJECTIVE: To provide a description of an emerging neuroimaging methodology, near
      infrared spectroscopy (nIRS), and a potential educational application of the
      unique aspects of this technology. SUMMARY: nIRS is documented for its potential
      as a personal, portable, brain imaging system that may prove useful for cerebral
      monitoring in applied settings such as home, school, and work. The basis of nIRS
      brain imaging is reviewed, with summary descriptions of optical and neurovascular
      issues as well as a brief comparison to other brain imaging methodologies. Recent
      developments in nIRS technology are discussed, including ongoing validation
      efforts and potential applications for neuropsychologists. We describe one
      potential application of nIRS (i.e., educational neuroimaging) as an illustration
      of the use of nIRS technology and the potential expansion of the
      neuropsychologist's role in the educational setting. CONCLUSION: nIRS holds the
      potential of opening new clinical questions and opportunities for
      neuropsychologists, and may provide a low-cost means of repeatable, neurovascular
      monitoring in nonmedical settings.

PMID- 12802257
TI  - Light-dependent redistribution of visual arrestins and transducin subunits in
      mice with defective phototransduction.
AB  - PURPOSE: The light-dependent redistribution of phototransduction components in
      photoreceptor cells plays a role in light adaptation. Upon illumination, rod and
      cone arrestins (Arr and cArr) translocate from the inner to the outer segments
      while transducin subunits (Talpha, Tbetagamma) translocate in the opposite
      direction. The underlying translocation mechanisms are unclear. This study
      examines these previously demonstrated translocation in mice with defective
      phototransduction. METHODS: The distribution of Arr, cArr, Talpha, and Tbetagamma
      was examined using immunoblotting and immunocytochemistry in dark- and light
      adapted single knockout mice lacking G-protein coupled receptor kinase 1 (Grk1-/
      ) and double knockout mice lacking GRK1 and transducin alpha subunit (Grk1-/
      /Gnat1-/-), or lacking GRK1 and arrestin (Grk1-/-/Arr-/-). RESULTS: Arr
      redistributed in the light to the outer segments in Grk1-/- mice as well as in
      Grk1-/-/Gnat1-/- double knockout retinas. Immunoblotting revealed that
      approximately 25-50% of Arr associated with the membrane in light-adapted wild
      type, Grk1-/- and Gnat1-/-/Grk1-/- mouse retinas. In contrast, cArr did not
      stably associate with light-adapted membranes in either wild-type or Grk1-/-
      retinas under our experimental conditions, but redistributed to the cone outer
      segments in a light-dependent manner. The redistribution of transducin subunits
      to the inner segments in light occurred in both wild-type and Grk1-/-/Arr-/-
      double knockout photoreceptors. However, Tbetagamma subunits did not redistribute
      in the absence of Talpha, suggesting that transducin only translocates as an
      intact heterotrimer. CONCLUSIONS: We conclude that in rods, Arr redistribution
      requires neither rhodopsin phosphorylation nor phototransduction, suggesting the
      presence of another light-dependent pathway to trigger translocation. In cones,
      the light-dependent movement of cArr appears to be independent of stable
      association with the cone pigments. The light-dependent translocations of Arr and
      transducin subunits in opposite directions appear to be based on independent
      mechanisms.

PMID- 12802259
TI  - Leadership challenges for carotid disease in the 21st century.

PMID- 12802258
TI  - Effect of curcumin on galactose-induced cataractogenesis in rats.
AB  - PURPOSE: Curcumin, the active principle of turmeric, has been shown to have both
      antioxidant and hypoglycemic activity in vitro and in vivo. The purpose of this
      study was to investigate the effect of curcumin on the onset and maturation of
      galactose induced cataract. METHODS: Sprague-Dawley rats (21 days old) were
      divided into 5 groups. The control group (A) received an AIN-93 diet, the
      galactose group (B) received 30% galactose in the diet, the test groups (C and D)
      received the B group diet plus 0.002% and 0.01% curcumin respectively, and group
      (E) received the control diet plus 0.01% curcumin, all for a period of 4 weeks.
      Cataract progression due to galactose feeding was monitored by slit lamp
      microscope and classified into 4 stages. At the end of the experiment biochemical
      parameters such as lipid peroxidation, aldose reductase (AR), sorbitol
      dehydrogenase (SDH), reduced glutathione, protein content, and protein carbonyls
      were measured in the lens. Advanced glycated end products (AGE) and protein
      oxidation were measured by AGE and tryptophon fluorescence respectively.
      Crystallin profile was analyzed by size exclusion chromatography (HPLC). RESULTS:
      Slit lamp microscope observations indicated that curcumin at 0.002% (group C)
      delayed the onset and maturation of cataract. In contrast even though there was a
      slight delay in the onset of cataract at the 0.01% level (group D), maturation of
      cataract was faster when compared to group B. Biochemical analysis showed that
      curcumin at the 0.002% level appeared to exert antioxidant and antiglycating
      effects, as it inhibited lipid peroxidation, AGE-fluorescence, and protein
      aggregation. Though the reasons for faster onset and maturation of cataract in
      group D rats was not clear, the data suggested that under hyperglycemic
      conditions higher levels of curcumin (0.01%) in the diet may increase oxidative
      stress, AGE formation, and protein aggregation. However, feeding of curcumin to
      normal rats up to a 0.01% level did not result in any changes in lens morphology
      or biochemical parameters. CONCLUSIONS: These results suggest that curcumin is
      effective against galactose-induced cataract only at very low amounts (0.002%) in
      the diet. On the other hand at and above a 0.01% level curcumin seems to not be
      beneficial under hyperglycemic conditions, at least with the model of galactose
      cataract.

PMID- 12802260
TI  - Management of infected grafts and mycotic aneurysms of the aorta using
      cryopreserved homografts.
AB  - OBJECTIVE: To evaluate the efficacy of the treatment of infected prosthetic
      grafts and mycotic aneurysms of the aorta with cryopreserved homografts.
      MATERIALS AND METHODS: Between April 1994 and May 2002, 15 cryopreserved aortic
      homografts were used in 13 patients in the thoracic and abdominal aortic position
      with supplementary omental or pectoral muscle wrapping for infected grafts
      (n=11), and mycotic aneurysms (n=2) (mean age: 57.5). RESULTS: One patient died
      due to multiorgan failure and the other due to postoperative cerebral hemorrhage
      (15.38%). Another patient died four months after the operation due to septic
      arthritis, and coronary heart disease. Ten patients are still alive without
      evidence of infection (76.92%) during a follow up of 44+/-23.03 (range 4-71)
      months. CONCLUSION: The use of cryopreserved homografts with supplementary
      omentum and/or muscle flap coverage, assures an anatomical reconstruction with
      good results in this difficult group of patients.

PMID- 12802261
TI  - Long-term effectiveness of operative procedures for Stanford type A aortic
      dissections.
AB  - BACKGROUND: To evaluate long-term effectiveness of strategies for managing the
      aortic root and distal aorta in type A dissections. METHODS: From 1990 to 1999,
      50 patients (32 men, 64.07%; 18 women, 36.0%; mean age 57.4 y +/- 11.1) underwent
      operation for ascending aortic dissection. Surgical strategies included aortic
      root replacement with a composite graft (21/50; 42.0%), valve replacement with
      supracoronary ascending aortic graft (3/50, 6%), and valve preservation or repair
      (26/50; 52.0%). RESULTS: Overall hospital mortality rate was 18.0%. Follow-up was
      completed for 47 patients (94.0%) and ranged from 1 month to 10.5 years (mean
      28.8 months). Actuarial survival for patients discharged from the hospital was
      84% at 1 year, 75% at 5 years, and 66% at 10 years. There was no significant
      difference between the various procedures regarding mortality, neurological
      complications, long term survival and proximal re-operations. The ascending aorta
      alone was replaced in 8/50 patients (16%), ascending and hemiarch in 30/50
      patients (60%) and arch and proximal descending aorta in 12/50 patients (24%)
      Hospital mortality (11.5, 20.0 and 16.7% respectively; p > 0.05) and 5- and 10
      year survival (p > 0.05) were not statistically dependent on the extension of the
      resection distally. Residual distal dissection was not associated with a decrease
      in late survival. With regard to emergency surgery (36/50) there was no
      significant difference in hospital mortality (p > 0.05) and 5 year survival (p >
      0.05) between those who had undergone coronary angiography (19/36; 52.8%) on the
      day of surgery with those who had not (17/36; 47.2%). CONCLUSIONS: Preservation
      or repair of the aortic valve can be recommended in the majority of patients with
      type A dissection. Distal extension of the resection does not increase surgical
      risk. Residual distal dissection does not decrease late survival. Preoperative
      coronary angiography may not affect survival in patients undergoing emergency
      surgery.

PMID- 12802262
TI  - Natural history of the ectatic aorta.
AB  - OBJECTIVES: To define the natural history of ectatic abdominal aortas and to
      assess the clinical need for follow-up. DESIGN: Abdominal aortas were considered
      ectatic if they were diffusely and irregularly dilated with a diameter less than
      3 cm. Ectatic aortas were identified either by AAA screening or as incidental
      findings. Patients who had only one scan were excluded from the study. Clinical
      data were analysed. SETTING: Two district general hospitals in Wales and England.
      SUBJECTS: 116 patients (90 men). RESULTS: : The median age of patients was 71
      years (range 48-90). Co-existing risk factors included hypertension (75), IHD
      (22), PVD (8), diabetes (3), COAD (14), stroke (5), popliteal aneurysm (1),
      malignant disease (3) and 4 had a family history of AAA. The median follow-up was
      24 months (range 5-72). The median and maximum growth rate of the ectatic aortas
      were 0.65 and 14.4 mm/year respectively. In three patients the expansion rate was
      more than 5 mm/year. In 22 patients the ectatic aorta became aneurysmal, reaching
      a diameter greater than 3 cm. There were no ruptures and no elective repairs. Two
      deaths occurred due to IHD. CONCLUSIONS: : This study demonstrates that if
      ectatic aortas do expand they do so very slowly. However, 22 of the 116 (19%)
      became aneurysmal in a follow-up of two years. Once identified ectatic aortas
      should be scanned at intervals of three years.

PMID- 12802263
TI  - Operative risk factors of type A aortic dissection: analysis of 252 consecutive
      patients.
AB  - OBJECTIVE: We examined operative risk factors for postoperative death after
      surgery for acute type A aortic dissection. METHODS: Between 1974 and 1999, 252
      patients, 163 men and 89 women (mean+/-SD age, 58+/-12 years) underwent surgery
      for acute type A aortic dissection. Fifty-eight (23.0%) were in cardiogenic shock
      at time of surgery. Most patients underwent ascending aorta replacement which was
      combined with aortic valve replacement by means of a composite graft in 30
      (11.9%) patients and an isolated aortic valve replacement in 16 (6.3%) patients.
      RESULTS: The overall operative mortality rate was 25.0% (n=63); 27.0% for
      patients operated upon with aortic cross-clamping, 23.7% after deep hypotherm
      circulatory arrest and 23.3% after antegrade selective cerebral perfusion (ASCP)
      (p=0.73). Multivariate analysis revealed iatrogenic dissection (p=0.0096, odds
      ratio=5.7), preoperative cardiopulmonary resuscitation (p=0.0095, odds ratio=5.5)
      and every quarter of an hour longer extracorporeal circulation (p=0.049, odds
      ratio=1.1) as independent risk factors for operative mortality. Aortic valve
      replacement or Bentall procedure (p=0.0185, odds ratio=0.3) were protective
      factors. There were 44 new postoperative strokes: 4.7% in the group operated upon
      with and 20.1% in the group without ASCP (p=0.01). CONCLUSION: In order to avoid
      cardiogenic shock and preoperative cardiopulmonary resuscitation, patients with
      acute type A aortic dissection should be treated promptly. The choice to use an
      aortic valve prosthesis or Bentall procedure when applicable seems to benefit the
      postoperative early survival. The risk of new postoperative neurological events
      might be reduced by avoiding the appliance of an aortic cross-clamp and by using
      ASCP.

PMID- 12802264
TI  - Endoluminal aortic shunting for distal perfusion during thoracic aortal cross
      clamping in a pig model.
AB  - PURPOSE OF THE STUDY: To investigate the haemodynamic properties of a direct
      endovascular aortic shunt to maintain distal aortic perfusion as an alternative
      of a distal shunt (left-left-, Gott shunt) in thoracic aortic aneurysm repair.
      METHODS: A shunt was developed and tested in an in vitro model which should be
      capable of transporting a flow of 3-4 L/min with a decrease in blood pressure <
      20 mmHg. Thereupon the shunt was tested in an in vivo experiment in six pigs to
      assess the possibility of its use with normal distal blood pressure. The shunt
      was inserted in the thoracic aorta and stayed in place for 1.5 h. Parameters were
      measured at six time intervals to assess organ perfusion, -function, cardiac
      output, proximal- and distal blood pressure and aortic- and shunt flow. PRINCIPLE
      FINDINGS: The mean blood flow through the shunt was 2.5 L/min. The difference of
      the mean blood pressure over the shunt was on average 14.20 mmHg. Parameters for
      coagulation disturbance and organ ischaemia were tested. The decrease in mean
      thrombocyte count was 299-158 (p<0.02). The venous lactate and the venous
      mesenteric lactate as parameters for intestinal ischemia did not increase
      significantly. No significant changes occurred in angiotensin II levels.
      Pulsatile flow was maintained but significantly suppressed (60%) distal from the
      shunt. The clamp time needed to insert the shunt and the venous mesenteric
      lactate, as well as the venous lactate, showed high correlation, r(s) = 0.9
      (p<0.05) and r(s) = 0.94 (p<0.01). This also accounted for the 2nd clamp time,
      both r(s) = 0.95 (p<0.05). CONCLUSION: The shunt is capable of transporting a
      blood flow of 2-4 L/min with an acceptable decrease in distal blood pressure.
      However, the time, needed to insert the shunt, was significantly associated with
      parameters of organ ischaemia.

PMID- 12802265
TI  - EuroSCORE overestimates the cardiac operative risk.
AB  - INTRODUCTION: It was the purpose of our study to assess the validity of EuroSCORE
      (European system for cardiac operative risk evaluation) in our patient
      population. MATERIALS AND METHODS: Between March 1999 and August 2001,
      information on risk factors and mortality was collected for 1123 consecutive
      adult patients undergoing heart surgery with cardiopulmonary bypass. EuroSCORE
      was used for risk stratification. Mean age +/- standard deviation was 58.6 +/-
      10.9 and 29.1% of the patients were female. The area under the receiver operating
      characteristic (ROC) curve was calculated as an index for the predictive value of
      the scoring system. RESULTS: The area under the ROC curve was 0.824 for all
      patients and 0.828 for the isolated CABG subgroup which shows an excellent
      predictive ability. When the scoring system was applied in low, medium, and high
      risk groups, there was no overlap between 95% confidence intervals of observed
      and expected mortality in all three groups both for the isolated CABG cases and
      for all patients. Decreased left ventricular ejection fraction, emergent
      operation, and preoperative unstable angina requiring i.v. nitrate treatment were
      significant predictive variables for early mortality. CONCLUSION: EuroSCORE is a
      simple and objective system for predicting the risk of heart surgery. The
      predictive power of the EuroSCORE is excellent, however it seems that mortality
      is considerably overestimated by this score.

PMID- 12802266
TI  - Integrated approach to off-pump coronary artery bypass surgery.
AB  - BACKGROUND: The Off-Pump Coronary Artery Bypass (OPCAB) technique is becoming
      more popular in many cardiac units throughout the world. This relatively new
      technique has prompted surgeons and anaesthetists to review and modify the
      routine approach to Coronary Artery Bypass Surgery (CABG). In this study we
      reviewed and analysed the outcome of an integrated anaesthetic and surgical peri
      operative approach that allowed routine use of OPCAB and avoided the use of
      cardiopulmonary bypass (CPB). METHODS: We reviewed and analysed the data on the
      first consecutive 285 patients who were operated on using the OPCAB technique.
      These represent our initial experience with applying the OPCAB technique non
      selectively for all patients over a period of 16 months. RESULTS: All patients
      had at least 2-vessel disease. 807 grafts were performed (mean 2.8 per patient)
      of which 647 (80%) were arterial (mean 2.3 per patient). 179 (63%) patients
      underwent total arterial revascularization. Eight patients required
      cardiopulmonary bypass; all other operations were completed off-pump.
      Complications--mortality 3 (1%); renal failure 24 (8%); stroke 3 (1%) and atrial
      fibrillation 60 (21%). CONCLUSION: This retrospective analysis shows that
      provided a combined and integrated anaesthetic and surgical approach is used,
      beating heart technique for CABG can be safely offered to all patients with a
      good outcome.

PMID- 12802268
TI  - The frequency of pleural effusions after Bellovac drainage following coronary
      bypass grafting.
AB  - BACKGROUND: A common postoperative complication after CABG with internal mammary
      artery (IMA) harvest is the evolution of a pleural effusion. Our aim was to see
      if the intra-operative insertion of a Bellovac drain to the pleural cavity, with
      drainage continuing for 4-days post operation, eliminates the complication of
      pleural effusion. METHODS: Using our computerised audit database, 500 consecutive
      patients were identified who had undergone CABG including at least one internal
      mammary graft by a single consultant at Blackpool Victoria Hospital. All these
      patients received Bellovac drainage for 4 days on the side of the harvested IMA.
      The chest X-ray reports were retrospectively collected from the hospital computer
      databases. The 4-day post-operative, and the 6-week post-operative films were
      found. In the cases where no consultant radiologist report was found J.D.
      reviewed the film, and any abnormalities were also reviewed by R.W.J.M. RESULTS:
      Out of 500 radiographs, six patients (1.2%) died, 25 patients had no traceable
      record of a chest X-ray, 434 patients had an entirely normal chest X-ray and 461
      patients had no effusion at 6 weeks. Six patients had a small effusion at 6
      weeks, two had a moderate effusion successfully treated conservatively, and no
      patients had a pleural effusion that required drainage. CONCLUSION: In patients
      undergoing coronary arterial bypass grafting with internal mammary artery
      harvest, the intra-operative insertion of a Bellovac drain on the side of the
      harvested IMA reduces the risk of postoperative pleural effusions

PMID- 12802267
TI  - CABG 15-years after left pneumonectomy: feasibility of off-pump approach.
AB  - We report the case of a 70-year-old man who underwent off-pump coronary artery
      bypass grafting 15-years after left pneumonectomy. He had significant two-vessel
      coronary artery disease. Comorbidities included poor ventricular function and
      impaired respiratory function. Operative risks in this clinical setting is
      increased. Our patient underwent off-pump CABG x 2. Thoracic epidural analgesia
      was also used to facilitate post-operative recovery. The patient was extubated an
      hour after the end of the procedure. The role of off-pump surgery in this high
      risk population and the use of stabilizing devices in these extreme anatomical
      situations is discussed.

PMID- 12802269
TI  - Aortoventriculoplasty in a patient with complex left ventricular outflow tract
      obstruction, mitral valve stenosis and aneurysm of the ascending aorta.
AB  - We describe a new method of aortoventriculoplasty in a patient with calcified
      mitral stenosis, aortic valvular stenosis, severe left ventricular outflow tract
      obstruction, and aneurysm of the ascending aorta. This complex pathology was
      successfully treated with replacement of both the valves and a tubular dacron
      graft. The proximal end of the dacron tube was tailored as a patch for the repair
      of the ventricular septum and the aortic root, and the distal end was anastomosed
      to the distal ascending aorta. The patient had an uneventful recovery and
      postoperative echocardiography showed no significant residual gradient on the
      left ventricular outflow tract.

PMID- 12802270
TI  - High output cardiac failure due to iatrogenic A-V fistula in scar: a report of a
      case and review of the literature.

PMID- 12802271
TI  - Survival for three years after intramyocardial high malignant non-Hodgkin
      lymphoma.

PMID- 12802274
TI  - c-Cbl is a critical modulator of the Ron tyrosine kinase receptor.
AB  - Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein
      (MSP), activates multiple signaling pathways by recruiting several positive
      regulators to a multifunctional docking site. Here we show that stimulation by
      MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the
      multifunctional docking site as well as to a juxtamembrane tyrosine
      autophosphorylation site. c-Cbl recruitment to these two sites results in
      polyubiquitylation of Ron molecules, which are subsequently sorted for
      endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and
      its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl
      are found also in physical complexes that include Grb2, these associations are
      insufficient for productive ubiquitylation of Ron. Our results shed light on the
      mechanism of receptor desensitization mediated by c-Cbl and its binding partner
      Grb2.

PMID- 12802275
TI  - Beta-catenin expression in Dupuytren's disease: potential role for cell-matrix
      interactions in modulating beta-catenin levels in vivo and in vitro.
AB  - Dupuytren's disease (DD) is a superficial fibromatosis of the hand. Although the
      molecular mechanisms responsible for this disease are unknown, recent studies
      suggest that beta-catenin may be a key factor involved in fibromatosis. In this
      study, we analysed the in vivo and in vitro expression levels of beta-catenin in
      DD, using surgical specimens and primary cell lines. Although no somatic
      mutations (exon 3) of beta-catenin were detected, Western blot analysis revealed
      high levels of beta-catenin in diseased palmar fascia, and low to undetectable
      levels of beta-catenin in patient-matched normal palmar fascia.
      Immunohistochemistry analysis showed high levels of beta-catenin expression
      within the disease fascia, as well as cytoplasmic and nuclear accumulations of
      the protein. Immunoprecipitation of beta-catenin from seven patient lesions
      showed the protein to be tyrosine phosphorylated. Lastly, Western analysis of
      three patient-matched (disease and normal fascia) primary cell cultures showed
      significantly elevated levels of beta-catenin in disease cells cultured in three
      dimensional collagen lattices. This is the first extensive in vivo and in vitro
      characterization of beta-catenin in DD, and the first to suggest that the
      extracellular matrix may play an important role in modulating beta-catenin
      stability in DD.

PMID- 12802276
TI  - Regulation of Hoxb2 by APL-associated PLZF protein.
AB  - The PLZF gene is translocated in a subset of all-trans-retinoic acid resistant
      acute promyelocytic leukaemia (APL) cases, encodes a DNA binding transcription
      factor and is expressed highly in haematopoietic progenitor cells as well
      developing central nervous system (CNS). The spatially restricted and temporally
      dynamic pattern of PLZF expression in the developing CNS suggested that it might
      play a role in the circuitry regulating hindbrain segmentation. We have now
      identified a PLZF binding site (PLZF-RE) in an enhancer region of Hoxb2 that
      itself is required for directing high-level expression in rhombomers 3 and 5 of
      the developing hindbrain. The wild-type r3/r5 enhancer linked to a heterologous
      promoter was responsive to regulation by PLZF, and this activity was lost in
      variants containing a mutated PLZF-RE. Compared with the wild-type protein, the
      binding of the APL-associated reciprocal RARalpha-PLZF fusion to PLZF-RE was much
      stronger, suggesting that the N-terminal PLZF sequences missing from the fusion
      may play a role in the regulation of DNA binding. Consistent with this, the N
      terminal POZ domain was required for cooperative binding of PLZF to a
      multimerized PLZF-RE. In the context of the r3/r5 enhancer, the PLZF-RE
      cooperated for PLZF binding with an additional A/T-rich motif positioned
      downstream of the PLZF-RE. This A/T motif was previously shown to be essential
      for the regulation of Hoxb2 expression in r3 and r5 in cooperation with another
      Kruppel-like zinc finger protein Krox 20. The presence of both the PLZF-RE and
      the A/T-rich motif was required for a maximal effect of PLZF on a heterologous
      promoter and was essential in vivo to direct the expression of a lacZ reporter in
      the chick neural tube. Hence, both PLZF and Krox20 cooperate with a common A/T
      motif in mediating in vivo activity of the Hoxb2 enhancer. Our findings indicate
      that Hoxb2 is a direct target for regulation by PLZF in the developing CNS and
      suggest that deregulation of Hox gene expression may contribute to APL
      pathogenesis.

PMID- 12802277
TI  - Attenuation of the TGF-beta-Smad signaling pathway in pancreatic tumor cells
      confers resistance to TGF-beta-induced growth arrest.
AB  - We have investigated the mechanism whereby tumor cells become resistant to the
      antiproliferative effects of transforming growth factor (TGF)-beta, while
      maintaining other responses that can lead to increased malignancy and
      invasiveness. TGF-beta signaling results in nuclear accumulation of active Smad
      complexes which regulate transcription of target genes. Here we show that in two
      pancreatic carcinoma cell lines, PT45 and Panc-1, that are resistant to TGF-beta
      induced growth arrest, the TGF-beta-Smad signaling pathway is attenuated compared
      with epithelial cells that are sensitive to the antiproliferative effects of TGF
      beta (HaCaT and Colo-357). In PT45 and Panc-1 cells, active Smad complexes remain
      nuclear for only 1-2 h compared with more than 6 h in HaCaT and Colo-357 cells.
      The attenuated pathway in PT45 and Panc-1 cells correlates with low levels of TGF
      beta type I receptor and results in an altered expression profile of TGF-beta
      inducible genes required for cell cycle arrest. Most significantly, expression of
      the CDK inhibitor, p21(Cip1/WAF1), which is required for TGF-beta-induced growth
      arrest in these cells, is not maintained. Moreover, we show that artificially
      attenuating the TGF-beta-Smad signaling pathway in HaCaT cells is sufficient to
      prevent TGF-beta-induced growth arrest. Our results demonstrate that the duration
      of TGF-beta-Smad signaling is a critical determinant of the specificity of the
      TGF-beta response.

PMID- 12802278
TI  - Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation.
AB  - Transformation suppressor Pdcd4 is downregulated in transformed (Tx) mouse
      epidermal JB6 RT101 cells relative to transformation-resistant (P-) and
      susceptible (P+) variants. Whether Pdcd4 downregulation is necessary not only to
      induce transformation but also to maintain tumor phenotypes has not been
      determined previously. In the present study, overexpression of Pdcd4 cDNA in
      stably transfected RT101 cells resulted in 40% fewer anchorage-independent
      colonies that were smaller in size than the vector control colonies, indicating
      that elevated Pdcd4 expression is sufficient to suppress tumor phenotype.
      Transient transfection of Pdcd4 expression plasmid and 4 x AP-1 reporter gene
      showed that activation of AP-1-dependent transcription was inhibited by Pdcd4
      expression in a concentration-dependent manner. In contrast, Pdcd4 did not
      inhibit serum response element-dependent transcription, indicating specificity.
      In a Gal4 fusion assay, Pdcd4 specifically inhibited activation of c-Jun and c
      Fos activation domains, but did not inhibit activation of JunB, JunD, Fra-1, or
      Fra-2. Gel mobility shift assay demonstrated that c-Jun is the major component
      detected in the AP-1 complex in RT101 cells. Previous studies suggested that AP-1
      activity is required for maintaining the transformed phenotype in RT101 cells.
      Thus, Pdcd4 suppresses tumor phenotype by inhibiting AP-1-dependent
      transcription, possibly through inhibiting c-Jun and c-Fos activation.

PMID- 12802279
TI  - Protein kinase inhibitor 2-aminopurine overrides multiple genotoxic stress
      induced cellular pathways to promote cell survival.
AB  - 2-Aminopurine (2-AP) is an adenine analog shown to cause cells to bypass chemical
      and radiation-induced cell cycle arrest through as-yet unidentified mechanisms.
      2-AP has also been shown to act as a kinase inhibitor. Tumor suppressor p53 plays
      an important role in the control of cell cycle and apoptosis in response to
      genotoxic stress. We were interested in examining the effect of 2-AP on p53
      phosphorylation and its possible consequences on checkpoint control in cells
      subjected to various forms of DNA damage. Here, we show that 2-AP suppresses p53
      phosphorylation in response to gamma radiation, adriamycin, or ultraviolet
      treatment. This is partly explained by the ability of the kinase inhibitor to
      inhibit ATM or ATR activities in vitro and impair ATM- or ATR-dependent p53
      phosphorylation in vivo. However, 2-AP is also capable of inhibiting p53
      phosphorylation in cells deficient in ATM, DNA-PK, or ATR suggesting the
      existence of multiple pathways by which this kinase inhibitor modulates p53
      activation. Biologically, the 2-AP-mediated inhibition of p53 stabilization
      enables wild-type p53-containing cells to bypass adriamycin-induced G(2)/M
      arrest. In the long term, however, 2-AP facilitates cells to resist DNA damage
      induced cell death independently of p53.

PMID- 12802280
TI  - Inactivation of hTERT transcription by Tax.
AB  - Telomerase expression is the hallmark of tumor cells in which this
      ribonucleoprotein complex preserves chromosome integrity by maintaining telomere
      length and thereby prevents cell death. However, recent data support a role of
      the combination of p53 and telomerase inactivation in initiating genetic
      instability that promotes malignant transformation. Through its pleiotropic
      effects on infected T-cell metabolism, the human T-cell leukemia virus type 1
      (HTLV-1) oncoprotein Tax plays a central role in leukemogenesis. Here, we show
      that Tax inhibits human telomerase reverse transcriptase (hTERT) transcription,
      which is the rate-limiting factor of telomerase activity. This inhibitory effect,
      that occurs in competition with c-Myc through a canonical c-Myc binding site
      within the hTERT promoter, results in a decreased telomerase activity of Tax
      expressing cells. This is the first demonstration of hTERT inhibition by an
      oncogene. Tax, which is only expressed in preleukemic cells, triggers infected T
      cell cycle and keeps these cells cycling while inactivating p53. We propose that,
      in combination with these effects, hTERT repression by Tax at an early phase of
      carcinogenesis might contribute to the massive ploidy changes associated with the
      development of HTLV-1-associated malignancies.

PMID- 12802281
TI  - Combination of microdissection and microarray analysis to identify gene
      expression changes between differentially located tumour cells in breast cancer.
AB  - Comparison of gene expression changes between cancer cells at the periphery and
      in the centre of breast cancers was performed using a combination of
      microdissection and microarray analysis. Cancer cells from the two areas were
      pooled separately from five patients with ductal carcinoma in situ and separately
      from five patients with frankly invasive cancer. Limited total RNA, 100-200 ng,
      from this microdissected tissue required use of the Atlas SMART trade mark Probe
      Amplification Kit to synthesize and amplify cDNA and make (33)P-labelled probes.
      Probes were then hybridized to Atlas Human Cancer 1.2 Arrays containing 1176
      known genes. Triplicate analysis revealed that 22 genes changed their expression
      levels in the periphery relative to the central region: 15 upregulated and seven
      downregulated (arbitrary threshold of 1.5-fold or greater). Differences in RNA
      levels were confirmed by quantitative real-time PCR for two of the genes and by
      changes in protein levels, detected by immunohistochemistry, for a couple of
      representative gene products. Thus, changes in gene expression associated with
      variation in microanatomical location of neoplastic cells can be detected within
      even small developing tumour masses.

PMID- 12802283
TI  - New benzo(b)thiophenesulphonamide 1,1-dioxide derivatives induce a reactive
      oxygen species-mediated process of apoptosis in tumour cells.
AB  - In this work, we describe the process of cell death induced by a series of new
      benzo(b)thiophenesulphonamide 1,1-dioxide derivatives (BTS) that have been
      selected as candidate antineoplastic drugs. Human leukaemic CCRF-CEM cells
      incubated with BTS undergo a typical apoptotic process that includes cell
      shrinkage, phosphatidylserine translocation to the cell surface, mitochondrial
      dysfunction, caspase activation, chromatin condensation and internucleosomal DNA
      degradation. Mitochondrial alterations included dissipation of the mitochondrial
      membrane potential, oxidation of the phospholipid cardiolipin, release of
      cytochrome c and uncoupling of the mitochondrial respiratory chain, leading to a
      decrease of the intracellular ATP pool. Activation of caspase-8, -9 and -3 takes
      place during BTS-induced apoptosis. Either the addition of the specific caspase-8
      inhibitor Z-IETD-fmk, or the overexpression of the antiapoptotic protein Bcl-2
      significantly prevented BTS-induced apoptosis, suggesting the involvement of both
      caspase-8-regulated and mitochondria-dependent signalling pathways in this
      process. BTS induce a significant increase in the production and accumulation of
      intracellular reactive oxygen species (ROS) that can be observed within minutes
      after drug addition. Moreover, cytochrome c release, caspase-3 activation and
      cell death can be completely abrogated by a previous incubation with the
      antioxidant N-acetyl-cysteine. These results suggest that ROS are essential
      mediators in BTS-induced apoptosis.

PMID- 12802282
TI  - BRCA1 shifts p53-mediated cellular outcomes towards irreversible growth arrest.
AB  - The tumor suppressor protein BRCA1 has been shown to enhance p53 transcription,
      whereas activated p53 represses BRCA1 transcription. To further understand the
      functional interaction of these proteins, we investigated the role of BRCA1 in
      p53-induced phenotypes. We found that BRCA1 when subjected to forced expression
      acts synergistically with wild-type p53, resulting in irreversible growth arrest,
      as shown by VhD mouse fibroblast cells expressing a temperature-sensitive mutant
      of p53. Furthermore, reintroduction of both BRCA1 and p53 into BRCA1(-/-)/p53(-/
      ) mouse embryonic fibroblasts markedly increased the senescence phenotype
      compared to that induced by p53 alone. In particular, we found that BRCA1
      expression attenuated p53-mediated cell death in response to gamma-irradiation.
      Moreover, microarray screening of 11 000 murine genes demonstrated that a set of
      genes upregulated by p53 is enhanced by coexpression of BRCA1 and p53, suggesting
      that BRCA1 and p53 exert a promoter selectivity leading to a specific phenotype.
      Taken together, our results provide evidence that BRCA1 is involved in p53
      mediated growth suppression rather than apoptosis.

PMID- 12802284
TI  - Metastatic lymph node 64 (MLN64), a gene overexpressed in breast cancers, is
      regulated by Sp/KLF transcription factors.
AB  - MLN64, is invariably coamplified and coexpressed with erbB-2 in breast cancers.
      The human MLN64 and ERBB2 genes are positioned at less than 50 kb from each
      other, on chromosome 17q12. To understand the molecular basis of MLN64
      overexpression in cancer, the genomic region containing the MLN64 and ERBB2 genes
      was isolated and mapped. The two genes, DARPP32 and Telethonin, flanking MLN64
      respectively on its centromeric and telomeric sides, although coamplified, are
      not overexpressed in breast cancer cells, indicating that gene amplification is
      not sufficient to allow overexpression. The MLN64 minimal promoter was isolated
      and found to be a housekeeping gene promoter containing four potential Sp1
      binding elements. Using Sp1-deficient Drosophila SL2 cells, MLN64 promoter
      activity was induced in a dose-dependent manner by exogenous Sp1 addition.
      Furthermore, mutation of each individual Sp1 element resulted in a significant
      decrease in reporter gene activity, indicating that all the Sp1 binding elements
      are functional and act together to promote gene expression. Since the ERBB2
      promoter is also positively regulated by Sp1, this study indicates that MLN64 and
      ERBB2 genes share common transcriptional controls together with a physical link
      on chromosome 17q. We speculate that, in addition to the oncogenic potential of
      erbB-2 overexpression, the unbalanced action of MLN64 contributes to the poor
      clinical outcome of breast tumors bearing this amplified region.

PMID- 12802285
TI  - IL-10 signaling via IL-10E1 is dependent on tyrosine phosphorylation in the IL
      10R alpha chain in human primary prostate cancer cell lines.
AB  - Interleukin 10 (IL-10) stimulates rapid nuclear translocation and binding of a 22
      kDa protein, termed interleukin 10 enhancer 1 (IL-10E1), to a novel enhancer
      element (i.e. HTE-1) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene
      to upregulate TIMP-1 expression. IL-10E1 signaling involves tyrosine
      phosphorylation of the IL-10R JAK1 (Janus kinase) and TYK2 (tyrosine kinase)
      receptor kinases and tyrosine phosphorylation of two tyrosine moieties (Y57 and
      Y62) of a LIM domain of the IL-10E1 protein. In this paper, the studies showed
      that two tyrosine residues (Tyr(446) and Tyr(496)) located in the cytoplasmic
      domain of the IL-10R alpha chain were required for receptor function, and for
      phosphorylation and activation of IL-10E1. Immunoprecipitation studies revealed
      that 12 amino-acid peptides encompassing either of these two tyrosine residues in
      phosphorylated form coprecipitated IL-10E1 and blocked ligand-dependent IL-10E1
      phosphorylation in a cell-free system. In contrast, peptides containing serine
      substitutions for Tyr(446) and Tyr(496), and tyrosine-phosphorylated peptides
      containing Tyr(230) or Tyr(252/259) did not prevent IL-10E1 activation or
      signaling. To confirm these observations in vivo, fusion protein constructs were
      made between a modified form of green fluorescent protein or GFP and the intact
      IL-10E1 protein (IL-10E1-MmGFP) and n-terminal peptides of the IL-10E1 protein
      (i.e. nt-nls-MmGFP and mutant sequences identified as nt-nls mC61-MmGFP and nt
      nls mY57/mY62-MmGFP peptides). Confocal microscopy revealed that IL-10 triggered
      transport to the nucleus of IL-10E1-MmGFP, nt-nls-MmGFP, and nt-nls mC61-MmGFP by
      10-30 min in HPCA-10a (human prostrate cancer cells; derived from Gleason sum 10
      tumor tissue) cells. IL-10 failed to induce nuclear translocation of the
      mY57/mY62-MmGFP peptides with point mutations of the two tyrosine groups.
      Coinjection of nt-nls-MmGFP with the IL-10R Tyr(446) and Tyr(496) amino-acid
      residues completely blocked ligand signaling. Coinjection of peptides containing
      either serine substitutions for Tyr(446) and Tyr(496) or Tyr(230) and
      Tyr(252/259) failed to block nt-nls-MmGFP signaling. The data demonstrate that IL
      10E1 is directly recruited to the ligand-activated IL-10R by binding to specific
      phosphotyrosine groups which control tyrosine phosphorylation of the LIM domain
      of the IL-10E1 protein (i.e. Y57/Y62 groups) and IL-10E1 activation.

PMID- 12802286
TI  - Molecular processes of chromosome 9p21 deletions in human cancers.
AB  - Interstitial deletions of the chromosome 9p21 segment encoding the p16/CDKN2A
      tumor suppressor gene (i.e., 9p21 deletions) are frequently observed in a variety
      of human cancers. A majority of these deletions in lymphoid leukemia have been
      indicated to be mediated by illegitimate V(D)J recombination. In the present
      study, to elucidate the molecular processes of 9p21 deletions in nonlymphocytic
      malignancies, breakpoints for these deletions were analysed in 21 lung cancer
      cell lines and 32 nonlymphocytic cancer cell lines of nine other histological
      types. In all, 32 breakpoints in 21 lung cancer cell lines and 56 breakpoints in
      32 nonlung cancer cell lines were mapped in a 450-kb segment encompassing the
      CDKN2A locus with a 10-kb resolution. The largest number of breakpoints (i.e.,
      seven breakpoints in lung cancer and 12 breakpoints in nonlung cancers) was
      mapped in a 10-kb region containing the CDKN2A gene. More precise mapping of
      these seven and 12 breakpoints revealed that none of these breakpoints were
      located within 50-bp intervals to each other in this 10 kb region. Cloning and
      sequencing of breakpoints in 18 representative cell lines (six lung and 12
      nonlung cancers) further revealed that there were no significant homologies among
      breakpoints in these 18 cell lines. In 11 (61%) cell lines, 1-5-bp nucleotides
      were overlapped at breakpoint junctions. These results indicate that DNA double
      strand breaks triggering 9p21 deletions do not occur at specific DNA sequences,
      although they preferentially occur in or near the CDKN2A locus. It was also
      indicated that two broken DNA ends are rejoined by nonhomologous end-joining
      repair, preferentially utilizing microhomologies of DNA ends, in the occurrence
      of 9p21 deletions.

PMID- 12802287
TI  - Hemizygosity of Nf2 is associated with increased susceptibility to asbestos
      induced peritoneal tumours.
AB  - Biallelic NF2 gene inactivation is frequently found in human malignant
      mesothelioma. In order to assess whether NF2 hemizygosity may enhance
      susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma
      developed in mice presenting a heterozygous mutation of the Nf2 gene
      (Nf2(KO3/+)), after intraperitoneal inoculation of crocidolite fibres. Asbestos
      exposed Nf2(KO3/+) mice developed tumoural ascites and mesothelioma at a higher
      frequency than their wild-type (WT) counterparts (P&<0.05). Six out of seven
      mesothelioma cell lines established from neoplastic ascitic fluids of Nf2(KO3/+)
      mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein
      expression was found in these cells. The results show the importance of the NF2
      gene in mesothelial oncogenesis, the potential association of asbestos exposure
      and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may
      be a susceptibility factor to asbestos.

PMID- 12802288
TI  - Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic
      carcinoma.
AB  - Recently, we have characterized the Ras association domain family 1A gene
      (RASSF1A) at the segment 3p21.3, which is frequently lost in variety of human
      cancers and epigenetically inactivated in many types of primary tumors, such as
      lung, breast, kidney, prostate and thyroid carcinomas. Here, we investigated the
      methylation status of the RASSF1A CpG island promoter in the pathogenesis of
      pancreatic cancer. RASSF1A hypermethylation was detected in 29 out of 45 (64%)
      primary adenocarcinomas, in 10 out of 12 (83%) endocrine tumors and in eight out
      of 18 (44%) pancreatitis samples. In seven out of eight pancreas cancer cell
      lines, RASSF1A was silenced and was retranscribed after treatment with 5-aza-2'
      deoxycytidine. Additionally, we analysed the aberrant methylation frequency of
      cell cycle inhibitor p16(INK4a) and K-ras gene mutations in the pancreatic
      samples. p16 inactivation was detected in 43% of adenocarcinomas, in 17% of
      neuroendocrine tumors, in 18% of pancreatitis and in 63% of pancreas cancer cell
      lines. K-ras mutations were detected in 16 out of 45 (36%) primary
      adenocarcinomas. Pancreatic adenocarcinomas with K-ras mutation have
      significantly less RASSF1A methylation and vice versa (P=0.001, chi(2) test). In
      conclusion, our data indicate that inactivation of the RASSF1A gene is a frequent
      event in pancreatic cancer and suggest an inverse correlation between RASSF1A
      silencing and K-ras activation.

PMID- 12802289
TI  - Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into
      the human telomerase reverse transcriptase (hTERT) gene in liver and cervical
      cancers.
AB  - Chronic infections with the hepatitis B virus (HBV) and high-risk human
      papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma
      (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that
      almost invariably integrate into the host genome in invasive tumors. The viral
      integration sites occur throughout the genome, leading to the presumption that
      there are no preferred sites of integration. A number of viral integrations have
      been shown to occur within the vicinity of important cancer-related genes. In
      studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and
      three HPV integrations into the human telomerase reverse transcriptase (hTERT)
      gene. Detailed characterization of the integrations revealed that four
      integrations occurred within the hTERT promoter and upstream region and the fifth
      integration occurred in intron 3 of the hTERT gene. None of the integrations
      altered the hTERT coding sequence and all resulted in juxtaposition of viral
      enhancers near hTERT, with potential activation of hTERT expression. Our work
      supports the hypothesis that the sites of oncogenic viral integration are
      nonrandom and that genes at the sites of viral integration may play important
      roles in carcinogenesis.

PMID- 12802290
TI  - Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative
      transcriptional targets using cDNA microarray expression profiling of genetically
      defined Wilms' tumors.
AB  - The Wilms' tumor suppressor gene, WT1, functions as a transcriptional regulator
      that represses or activates the expression of a variety of putative target genes.
      However, it is not clear which genes are the biological targets of WT1, nor which
      cellular pathway(s) is critically altered in tumors as a result of WT1 mutation.
      To investigate in vivo the role of WT1 as a transcription factor in Wilms'
      tumors, we used cDNA microarrays to compare the expression of putative WT1 target
      genes in a set of 15 primary Wilmstumors carrying WT1-inactivating mutations
      versus a set of 16 tumors with no WT1 mutations. We hypothesized that the
      expression of direct downstream targets of WT1 that are relevant to tumor
      development would differ between these two genetically distinct sets of tumors.
      Using the Atlas Human Cancer 1.2 cDNA arrays to quantitate gene expression in the
      31 tumors, we found that the expression of one WT1 putative target gene, c-MYC,
      statistically significantly differed between the two sets of tumors and was
      upregulated in WT1-mutant tumors. This increase of relative gene expression for c
      MYC was confirmed using real-time reverse transcription-polymerase chain
      reaction. The differential expression of another putative target gene, EGR1,
      approached significance and was also upregulated in WT1-mutant tumors. These
      data, in addition to the coexpression of c-MYC and WT1 in embryonic renal
      mesenchyme, strongly suggest that c-MYC is a biologically relevant target of WT1
      in Wilmstumors.

PMID- 12802291
TI  - From red peril to red tape.

PMID- 12802292
TI  - Debate, what debate?

PMID- 12802293
TI  - Astronomers leap to defence of extra seconds in time debate.

PMID- 12802294
TI  - Public input sought on transgenic farming.

PMID- 12802295
TI  - All change as Argentina's science leader keeps his job.

PMID- 12802297
TI  - Quake triggers research expedition.

PMID- 12802296
TI  - Monsoon rains start to ease India's drought.

PMID- 12802298
TI  - Physicists doubt that 'corking' could help baseball's big hitter.

PMID- 12802299
TI  - Prairie-dog model offers hope of tackling monkeypox virus.

PMID- 12802300
TI  - Pumping row erodes hopes for underground lab.

PMID- 12802301
TI  - Car-safety lobby on collision course with researchers.

PMID- 12802302
TI  - Pollution fears put work at neutrino laboratory on hold.

PMID- 12802304
TI  - Russia's bioweapons labs: Still out in the cold.

PMID- 12802305
TI  - Rapid climate change: Gas leak!

PMID- 12802306
TI  - Why should we help politicians to wage war?

PMID- 12802307
TI  - DNA discoveries through crystallography.

PMID- 12802312
TI  - Functional information: Molecular messages.

PMID- 12802314
TI  - Meteoritics: A question of timing.

PMID- 12802317
TI  - High-energy physics: Into the fifth dimension.

PMID- 12802315
TI  - Human evolution: Out of Ethiopia.

PMID- 12802319
TI  - Astrophysics: Superficial resonance.

PMID- 12802318
TI  - Cognitive neuroscience: Practice doesn't make perfect.

PMID- 12802320
TI  - Evolutionary biology: Genes to make new species.

PMID- 12802321
TI  - Obituary: Harmon Craig (1926-2003).

PMID- 12802323
TI  - Super-tough carbon-nanotube fibres.

PMID- 12802324
TI  - Avian metabolism: Costs of migration in free-flying songbirds.

PMID- 12802325
TI  - Reticular synthesis and the design of new materials.
AB  - The long-standing challenge of designing and constructing new crystalline solid
      state materials from molecular building blocks is just beginning to be addressed
      with success. A conceptual approach that requires the use of secondary building
      units to direct the assembly of ordered frameworks epitomizes this process: we
      call this approach reticular synthesis. This chemistry has yielded materials
      designed to have predetermined structures, compositions and properties. In
      particular, highly porous frameworks held together by strong metal-oxygen-carbon
      bonds and with exceptionally large surface area and capacity for gas storage have
      been prepared and their pore metrics systematically varied and functionalized.

PMID- 12802326
TI  - Adaptive evolution drives divergence of a hybrid inviability gene between two
      species of Drosophila.
AB  - Speciation--the splitting of one species into two--occurs by the evolution of any
      of several forms of reproductive isolation between taxa, including the intrinsic
      sterility and inviability of hybrids. Abundant evidence shows that these hybrid
      fitness problems are caused by incompatible interactions between loci: new
      alleles that become established in one species are sometimes functionally
      incompatible with alleles at interacting loci from another species. However,
      almost nothing is known about the genes involved in such hybrid incompatibilities
      or the evolutionary forces that drive their divergence. Here we identify a gene
      that causes epistatic inviability in hybrids between two fruitfly species,
      Drosophila melanogaster and D. simulans. Our population genetic analysis reveals
      that this gene--which encodes a nuclear pore protein--evolved by positive natural
      selection in both species' lineages. These results show that a lethal hybrid
      incompatibility has evolved as a by-product of adaptive protein evolution.

PMID- 12802327
TI  - The magnetic field of an isolated neutron star from X-ray cyclotron absorption
      lines.
AB  - Isolated neutron stars are highly magnetized, fast-rotating objects that form as
      an end point of stellar evolution. They are directly observable in X-ray
      emission, because of their high surface temperatures. Features in their X-ray
      spectra could in principle reveal the presence of atmospheres, or be used to
      estimate the strength of their magnetic fields through the cyclotron process, as
      is done for X-ray binaries. Almost all isolated neutron star spectra observed so
      far appear as featureless thermal continua. The only exception is 1E1207.4-5209
      (refs 7-9), where two deep absorption features have been detected, but with
      insufficient definition to permit unambiguous interpretation. Here we report a
      long X-ray observation of the same object in which the star's spectrum shows
      three distinct features, regularly spaced at 0.7, 1.4 and 2.1 keV, plus a fourth
      feature of lower significance, at 2.8 keV. These features vary in phase with the
      star's rotation. The logical interpretation is that they are features from
      resonant cyclotron absorption, which allows us to calculate a magnetic field
      strength of 8 x 10(10) G, assuming the absorption arises from electrons.

PMID- 12802328
TI  - Contemporaneous formation of chondrules and refractory inclusions in the early
      Solar System.
AB  - Chondrules and calcium-aluminium-rich inclusions (CAIs) are preserved materials
      from the early history of the Solar System, where they resulted from thermal
      processing of pre-existing solids during various flash heating episodes which
      lasted for several million years. CAIs are believed to have formed about two
      million years before the chondrules. Here we report the discovery of a chondrule
      fragment embedded in a CAI. The chondrule's composition is poor in 16O, while the
      CAI has a 16O-poor melilite (Ca, Mg, Al-Silicate) core surrounded by a 16O-rich
      igneous mantle. These observations, when combined with the previously reported
      CAI-bearing chondrules, strongly suggest that the formation of chondrules and
      CAIs overlapped in time and space, and that there were large fluctuations in the
      oxygen isotopic compositions in the solar nebula probably synchronizing
      astrophysical pulses.

PMID- 12802329
TI  - Generation of nonclassical photon pairs for scalable quantum communication with
      atomic ensembles.
AB  - Quantum information science attempts to exploit capabilities from the quantum
      realm to accomplish tasks that are otherwise impossible in the classical domain.
      Although sufficient conditions have been formulated for the physical resources
      required to achieve quantum computation and communication, there is a growing
      understanding of the power of quantum measurement combined with the conditional
      evolution of quantum states for accomplishing diverse tasks in quantum
      information science. For example, a protocol has recently been developed for the
      realization of scalable long-distance quantum communication and the distribution
      of entanglement over quantum networks. Here we report the first enabling step in
      the realization of this protocol, namely the observation of quantum correlations
      for photon pairs generated in the collective emission from an atomic ensemble.
      The nonclassical character of the fields is demonstrated by the violation of an
      inequality involving their normalized correlation functions. Compared to previous
      investigations of non-classical correlations for photon pairs produced in atomic
      cascades and in parametric down-conversion, our experiment is distinct in that
      the correlated photons are separated by a programmable time interval (of about
      400 nanoseconds in our initial experiments).

PMID- 12802330
TI  - Ultrafast terahertz probes of transient conducting and insulating phases in an
      electron-hole gas.
AB  - Many-body systems in nature exhibit complexity and self-organization arising from
      seemingly simple laws. For example, the long-range Coulomb interaction between
      electrical charges has a simple form, yet is responsible for a plethora of bound
      states in matter, ranging from the hydrogen atom to complex biochemical
      structures. Semiconductors form an ideal laboratory for studying many-body
      interactions of electronic quasiparticles among themselves and with lattice
      vibrations and light. Oppositely charged electron and hole quasiparticles can
      coexist in an ionized but correlated plasma, or form bound hydrogen-like pairs
      called excitons. The pathways between such states, however, remain elusive in
      near-visible optical experiments that detect a subset of excitons with vanishing
      centre-of-mass momenta. In contrast, transitions between internal exciton levels,
      which occur in the far-infrared at terahertz (1012 s(-1)) frequencies, are
      independent of this restriction, suggesting their use as a probe of electron-hole
      pair dynamics. Here we employ an ultrafast terahertz probe to investigate
      directly the dynamical interplay of optically-generated excitons and unbound
      electron-hole pairs in GaAs quantum wells. Our observations reveal an unexpected
      quasi-instantaneous excitonic enhancement, the formation of insulating excitons
      on a 100-ps timescale, and the conditions under which excitonic populations
      prevail.

PMID- 12802331
TI  - The 'zero charge' partitioning behaviour of noble gases during mantle melting.
AB  - Noble-gas geochemistry is an important tool for understanding planetary processes
      from accretion to mantle dynamics and atmospheric formation. Central to much of
      the modelling of such processes is the crystal-melt partitioning of noble gases
      during mantle melting, magma ascent and near-surface degassing. Geochemists have
      traditionally considered the 'inert' noble gases to be extremely incompatible
      elements, with almost 100 per cent extraction efficiency from the solid phase
      during melting processes. Previously published experimental data on partitioning
      between crystalline silicates and melts has, however, suggested that noble gases
      approach compatible behaviour, and a significant proportion should therefore
      remain in the mantle during melt extraction. Here we present experimental data to
      show that noble gases are more incompatible than previously demonstrated, but not
      necessarily to the extent assumed or required by geochemical models. Independent
      atomistic computer simulations indicate that noble gases can be considered as
      species of 'zero charge' incorporated at crystal lattice sites. Together with the
      lattice strain model, this provides a theoretical framework with which to model
      noble-gas geochemistry as a function of residual mantle mineralogy.

PMID- 12802332
TI  - Pleistocene Homo sapiens from Middle Awash, Ethiopia.
AB  - The origin of anatomically modern Homo sapiens and the fate of Neanderthals have
      been fundamental questions in human evolutionary studies for over a century. A
      key barrier to the resolution of these questions has been the lack of substantial
      and accurately dated African hominid fossils from between 100,000 and 300,000
      years ago. Here we describe fossilized hominid crania from Herto, Middle Awash,
      Ethiopia, that fill this gap and provide crucial evidence on the location, timing
      and contextual circumstances of the emergence of Homo sapiens. Radioisotopically
      dated to between 160,000 and 154,000 years ago, these new fossils predate classic
      Neanderthals and lack their derived features. The Herto hominids are
      morphologically and chronologically intermediate between archaic African fossils
      and later anatomically modern Late Pleistocene humans. They therefore represent
      the probable immediate ancestors of anatomically modern humans. Their anatomy and
      antiquity constitute strong evidence of modern-human emergence in Africa.

PMID- 12802333
TI  - Stratigraphic, chronological and behavioural contexts of Pleistocene Homo sapiens
      from Middle Awash, Ethiopia.
AB  - Clarifying the geographic, environmental and behavioural contexts in which the
      emergence of anatomically modern Homo sapiens occurred has proved difficult,
      particularly because Africa lacked adequate geochronological, palaeontological
      and archaeological evidence. The discovery of anatomically modern Homo sapiens
      fossils at Herto, Ethiopia, changes this. Here we report on stratigraphically
      associated Late Middle Pleistocene artefacts and fossils from fluvial and lake
      margin sandstones of the Upper Herto Member of the Bouri Formation, Middle Awash,
      Afar Rift, Ethiopia. The fossils and artefacts are dated between 160,000 and
      154,000 years ago by precise age determinations using the 40Ar/39Ar method. The
      archaeological assemblages contain elements of both Acheulean and Middle Stone
      Age technocomplexes. Associated faunal remains indicate repeated, systematic
      butchery of hippopotamus carcasses. Contemporary adult and juvenile Homo sapiens
      fossil crania manifest bone modifications indicative of deliberate mortuary
      practices.

PMID- 12802334
TI  - The remarkable inefficiency of word recognition.
AB  - Do we recognize common objects by parts, or as wholes? Holistic recognition would
      be efficient, yet people detect a grating of light and dark stripes by parts.
      Thus efficiency falls as the number of stripes increases, in inverse proportion,
      as explained by probability summation among independent feature detectors. It is
      inefficient to detect correlated components independently. But gratings are
      uncommon artificial stimuli that may fail to tap the full power of visual object
      recognition. Familiar objects become special as people become expert at judging
      them, possibly because the processing becomes more holistic. Letters and words
      were designed to be easily recognized, and, through a lifetime of reading, our
      visual system presumably has adapted to do this as well as it possibly can. Here
      we show that in identifying familiar English words, even the five most common
      three-letter words, observers have the handicap predicted by recognition by
      parts: a word is unreadable unless its letters are separately identifiable.
      Efficiency is inversely proportional to word length, independent of how many
      possible words (5, 26 or thousands) the test word is drawn from. Human
      performance never exceeds that attainable by strictly letter- or feature-based
      models. Thus, everything seen is a pattern of features. Despite our virtuosity at
      recognizing patterns and our expertise from reading a billion letters, we never
      learn to see a word as a feature; our efficiency is limited by the bottleneck of
      having to rigorously and independently detect simple features.

PMID- 12802335
TI  - Control of dynamic CFTR selectivity by glutamate and ATP in epithelial cells.
AB  - Cystic fibrosis is caused by mutations in cystic fibrosis transmembrane
      conductance regulator (CFTR), an anion channel. Phosphorylation and ATP
      hydrolysis are generally believed to be indispensable for activating CFTR. Here
      we report phosphorylation- and ATP-independent activation of CFTR by cytoplasmic
      glutamate that exclusively elicits Cl-, but not HCO3-, conductance in the human
      sweat duct. We also report that the anion selectivity of glutamate-activated CFTR
      is not intrinsically fixed, but can undergo a dynamic shift to conduct HCO3- by a
      process involving ATP hydrolysis. Duct cells from patients with DeltaF508 mutant
      CFTR showed no glutamate/ATP activated Cl- or HCO3- conductance. In contrast,
      duct cells from heterozygous patients with R117H/DeltaF508 mutant CFTR also lost
      most of the Cl- conductance, yet retained significant HCO3- conductance. Hence,
      not only does glutamate control neuronal ion channels, as is well known, but it
      can also regulate anion conductance and selectivity of CFTR in native epithelial
      cells. The loss of this uniquely regulated HCO3- conductance is most probably
      responsible for the more severe forms of cystic fibrosis pathology.

PMID- 12802336
TI  - Pathogen-induced systemic plant signal triggers DNA rearrangements.
AB  - Plant genome stability is known to be affected by various abiotic environmental
      conditions, but little is known about the effect of pathogens. For example,
      exposure of maize plants to barley stripe mosaic virus seems to activate
      transposable elements and to cause mutations in the non-infected progeny of
      infected plants. The induction by barley stripe mosaic virus of an inherited
      effect may mean that the virus has a non-cell-autonomous influence on genome
      stability. Infection with Peronospora parasitica results in an increase in the
      frequency of somatic recombination in Arabidopsis thaliana; however, it is
      unclear whether effects on recombination require the presence of the pathogen or
      represent a systemic plant response. It is also not clear whether the changes in
      the frequency of somatic recombination can be inherited. Here we report a
      threefold increase in homologous recombination frequency in both infected and non
      infected tissue of tobacco plants infected with either tobacco mosaic virus or
      oilseed rape mosaic virus. These results indicate the existence of a systemic
      recombination signal that also results in an increased frequency of meiotic
      and/or inherited late somatic recombination.

PMID- 12802338
TI  - Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide
      intermediate.
AB  - The second messenger hydrogen peroxide is required for optimal activation of
      numerous signal transduction pathways, particularly those mediated by protein
      tyrosine kinases. One mechanism by which hydrogen peroxide regulates cellular
      processes is the transient inhibition of protein tyrosine phosphatases through
      the reversible oxidization of their catalytic cysteine, which suppresses protein
      dephosphorylation. Here we describe a structural analysis of the redox-dependent
      regulation of protein tyrosine phosphatase 1B (PTP1B), which is reversibly
      inhibited by oxidation after cells are stimulated with insulin and epidermal
      growth factor. The sulphenic acid intermediate produced in response to PTP1B
      oxidation is rapidly converted into a previously unknown sulphenyl-amide species,
      in which the sulphur atom of the catalytic cysteine is covalently linked to the
      main chain nitrogen of an adjacent residue. Oxidation of PTP1B to the sulphenyl
      amide form is accompanied by large conformational changes in the catalytic site
      that inhibit substrate binding. We propose that this unusual protein modification
      both protects the active-site cysteine residue of PTP1B from irreversible
      oxidation to sulphonic acid and permits redox regulation of the enzyme by
      promoting its reversible reduction by thiols.

PMID- 12802337
TI  - Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.
AB  - Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30)
      is a hormone secreted by adipocytes that acts as an antidiabetic and anti
      atherogenic adipokine. Levels of adiponectin in the blood are decreased under
      conditions of obesity, insulin resistance and type 2 diabetes. Administration of
      adiponectin causes glucose-lowering effects and ameliorates insulin resistance in
      mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and
      diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by
      an increase in fatty-acid oxidation through activation of AMP kinase and PPAR
      alpha. Here we report the cloning of complementary DNAs encoding adiponectin
      receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is
      abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly
      expressed in the liver. These two adiponectin receptors are predicted to contain
      seven transmembrane domains, but to be structurally and functionally distinct
      from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of
      AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they
      serve as receptors for globular and full-length adiponectin, and that they
      mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty
      acid oxidation and glucose uptake by adiponectin.

PMID- 12802339
TI  - Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B.
AB  - Protein tyrosine phosphatases regulate signal transduction pathways involving
      tyrosine phosphorylation and have been implicated in the development of cancer,
      diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests
      that the cellular redox state is involved in regulating tyrosine phosphatase
      activity through the reversible oxidization of the catalytic cysteine to
      sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic
      (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we
      report the crystal structures of the regulatory sulphenic and irreversible
      sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an
      important enzyme in the negative regulation of the insulin receptor and a
      therapeutic target in type II diabetes and obesity. We also identify a sulphenyl
      amide species that is formed through oxidation of its catalytic cysteine.
      Formation of the sulphenyl-amide causes large changes in the PTP1B active site,
      which are reversible by reduction with the cellular reducing agent glutathione.
      The sulphenyl-amide is a protective intermediate in the oxidative inhibition of
      PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols
      and signal a unique state of the protein.

PMID- 12802341
TI  - Wrapped in red tape.

PMID- 12802342
TI  - With the United States on high alert over the possibility of bioterror attacks,
      epidemiologists are in huge demand.

PMID- 12802343
TI  - The Bowman lecture. Towards an understanding of age-related macular disease.

PMID- 12802344
TI  - Ultrasound biomicroscopic evaluation of the traumatized eyes.
AB  - PURPOSE: To review causes for performing an ultrasound biomicroscopic (UBM)
      examination in traumatized eyes, to present common UBM findings of 109 eyes with
      a history of ocular trauma and to compare these findings according to the type of
      the trauma. MATERIALS AND METHODS: A total of 109 eyes with a history of
      mechanical ocular trauma, which underwent an UBM examination between December
      1996 and April 2002, were evaluated retrospectively. All cases were classified
      according to the criteria of the Ocular Trauma Classification Group and UBM
      findings were reviewed. For statistical ana- lyses, chi(2) test and Fisher's
      exact test were used. RESULTS: UBM examinations were performed for the evaluation
      of the zonules before cataract surgery (49.5%), examination of the anterior
      segment in the presence of media opacities (32.1%), detection of suspected ocular
      foreign bodies (10.1%) and the evaluation of ocular hypotony (8.3%). In all, 67
      eyes (61.5%) had a closed-globe injury, whereas 42 (38.5%) had an open-globe
      injury. The most common UBM findings in a closed-globe injury were zonular
      deficiency (64.2%), angle recession (43.3%), iridodialysis (17.9%), and
      dislocated lens (16.4%). The most common UBM findings in an open-globe injury
      were zonular deficiency (54.8%), iridodialysis (26.2%), peripheral anterior
      synechiae (PAS) (26.2%), and iridocorneal adhesion (19%). Among the common UBM
      findings, the angle recession was significantly higher (P<0.001) in closed-globe
      injury group and PAS formation was significantly higher (P<0.05) in open-globe
      injury group. CONCLUSIONS: UBM is particularly superior to other methods in the
      evaluation of the zonular status, angle recession, cyclodialysis, and the
      detection of small superficial and intraocular foreign bodies.

PMID- 12802345
TI  - Expression of CD18, CD49b, CD49c and CD49e on lens anterior capsules in human
      cataracts.
AB  - PURPOSE: To examine the lens epithelial cells obtained from the anterior lens
      capsules removed during cataract surgery and detect various subclasses of the
      cell surface adhesion molecules known as integrins. METHODS: The circular
      sections of anterior capsules with attached lens epithelial cells (LECs) were
      obtained during cataract surgery from 28 patients. The lens capsules were
      immunohistochemically stained. RESULTS: CD49b CD49c, CD49e, and CD18 were
      detected in varying degrees in specimens obtained from human cataractous lenses.
      The positive percentages were 33, 75, 33, and 20%, respectively. The most
      striking feature was the increasing staining profiles towards the edges of the
      capsules (away from the central part of the lens capsules) for CD49c, suggesting
      that the LECs showed higher immunoreactivity for this antibody. The
      immunoreactivity for CD49b and CD49e was weaker. This was absent for CD18 in the
      central part of the lens capsules. CONCLUSION: The positive expression of
      antibodies suggests that specific integrin subunits were expressed in LECs of
      human cataracts. These results suggest that lens epithelial cells expressing
      CD49b, CD49c, CD49e, and CD18 might be precursors in the process of anterior lens
      epithelial cell (A cell) adhesion, and hence play a role in anterior capsule
      opacification or in subsequent migration and a possible role in posterior capsule
      opacification.

PMID- 12802346
TI  - Efficacy of incisional vs punch biopsy in the histological diagnosis of
      periocular skin tumours.
AB  - AIMS: The aim of this study was to compare the accuracy of incisional and punch
      biopsy techniques in obtaining correct histological diagnosis of periorbital
      eyelid tumours. The technique of punch biopsy is presented and described in
      detail. METHODS: A retrospective analysis was made of 20 consecutive incisional
      biopsies and 20 consecutive punch biopsies. In each case, the histology obtained
      at biopsy was compared with that identified at the time of tumour excision.
      RESULTS: A total of 40 consecutive biopsies on 38 patients were analysed. The
      first 20 were incisional; the second 20 were punch biopsies. Of the 20 incisional
      biopsy specimens, 19 were confirmed accurate at the time of excision of the
      lesion. Of the 20 punch biopsies, 17 were confirmed accurate at the time of
      excision. These correspond to accuracy rates of 95 and 85%, respectively.
      CONCLUSIONS: Both incisional and punch biopsy techniques have relatively high
      accuracy rates and there is a high concordance between tissue diagnoses made by
      each of these techniques. Incisional techniques should preferably be performed on
      any atypical lesion. Punch biopsy is a quick and simple procedure. It is easy to
      perform in an outpatient environment and requires a minimum of surgical equipment
      and no specific surgical skills. If the site of biopsy is carefully chosen, this
      simple technique provides tissue specimens of adequate size and quality for
      accurate histology and is a most useful adjunct in the management of periocular
      tumours.

PMID- 12802347
TI  - Corneal surface changes in keratoconjunctivitis sicca. Part I: The surface
      proper. A non-contact photomicrographic in vivo study in the human cornea.
AB  - PURPOSE: To describe corneal surface changes in keratoconjunctivitis sicca (KCS).
      METHODS: In all 23 patients with KCS were examined with the slit lamp and
      photographed by non-contact photomicrography. RESULTS: Without staining, grey
      surface cells and small epithelial cysts were visible. Application of fluorescein
      sodium resulted in two types of micropunctuate (15-30 microm) staining, a
      nonfluorescent (yellow/brown) and a fluorescent (green) one, in brilliantly green
      staining of cysts, and in enlarging fluorescent (green) flecks (70-1600 microm)
      with propensity to confluence. The flecks often developed in inconspicuous areas
      and showed abnormal subsurface cells. Application of rose bengal resulted in more
      or less intensively red-stained cells measuring about 30 mm in diameter, often
      less (15-20 microm), with or without a centrally located nucleus, individual or
      gathered in small groups or larger patches, and in confluent staining. Smaller
      and larger cells, with or without nuclei, weakly or strongly stained, were often
      located close to each other. The smaller green flecks showed a few centrally
      located red-stained cells, and the larger ones showed many almost uniform small
      red-stained nucleated ones. CONCLUSIONS: Corneal epithelial surface disease in
      the present KCS patients consisted of unspecific features-such as increased light
      reflecting property (grey cells), disruptions of intercellular junctions
      (micropunctuate green fluorescein staining), pathological dye uptake
      (micropunctuate yellow/brown fluorescein and red rose bengal stainings), and
      epithelial oedema (microcysts)--and also of features that seemed to be disease
      specific. Such features were, with fluorescein sodium, focal disruptions of the
      epithelial barrier function manifesting in enlarging green flecks, and, with rose
      bengal, abundant nucleated cells, particularly small ones organised in foci. The
      nature of the abnormal subsurface cells present in the areas of the green flecks,
      and the mechanisms behind the focal involvement are unclear.

PMID- 12802348
TI  - Corneal surface changes in keratoconjunctivitis sicca. Part II: The mucus
      component. A non-contact photomicrographic in vivo study in the human cornea.
AB  - PURPOSE: Description of mucus on the corneal surface and in the precorneal tear
      film in keratoconjunctivitis sicca (KCS). METHODS: In all, 24 patients with KCS
      examined with slit lamp and by non-contact photomicrography. RESULTS: Material
      interpreted as mucus seemed to exist in three varieties: one optically dense,
      light reflecting, and with definite forms (fine threads, variously thick and long
      strands, sheet-like structures); one appearing as small clumps or patches of
      light-reflecting material adhering to the corneal surface; and one amorphous. All
      were present either per se, or in various combinations, with or without adherent
      cell debris. The mucus attached to abnormal (stainable) corneal surface cells.
      CONCLUSIONS: The formed material strongly resembles formed mucus found in samples
      from normal conjunctival surface; the light-reflecting clumps or patches adhering
      to the surface are possibly of the same origin. The nature of the amorphous
      material is unclear. Adherence of formed mucus to the corneal surface seems to be
      related to the presence of abnormal (stainable) surface cells.

PMID- 12802349
TI  - Effects of fibrovascular traction and pooling of tears on corneal topographic
      changes induced by pterygium.
AB  - AIM: To investigate the effects of fibrovascular traction and the pooling of
      tears at the pterygium apex on the corneal topographic changes induced by
      pterygium. METHODS: A total of 16 eyes of 14 cases with primary pterygium were
      included in the study. A computerized corneal topography system was used for
      corneal topography examinations. Baseline keratographs were taken two times at
      straight gaze. A repeat corneoscope photograph was immediately obtained in
      temporal gaze. Then the tears at the pterygium apex were dried with a cellulose
      sponge, and a new corneoscope photograph was immediately obtained without
      allowing one to blink. Corneal topographic maps (numeric maps) were divided into
      301 fields in 24 meridians. One colour was allocated to each field, representing
      its mean refractive power for all groups. In all eyes, keratometric astigmatism
      at the 3 mm central cornea and total mean corneal refractive power were found.
      Data were compared using paired-samples two-tailed t-tests. RESULTS: Keratometric
      astigmatism at the 3 mm central cornea was significantly reduced at the temporal
      gaze (3.10+/-2.34 D, t=3.40, P=0.027) and dried eyes (2.12+/-1.01 D, t=4.74,
      P=0.001) according to the first baseline measurement (4.31+/-1.91 D) of the total
      mean corneal refractive power was found to be 43.45+/-1.28 D (39.29-45.87) at the
      first baseline measurement. There was no change at the temporal gaze (43.54+/
      1.06 D, P>0.05). However, the total corneal refractive power was significantly
      higher in dried eyes (44.26+/-0.93 D, t=34.92, P<0.001). The steepest region of
      corneal topography was a superior quadrant, and the flattest area was a nasal
      quadrant at the baseline. At the temporal gaze, the cornea was significantly
      flatter in the superior and inferior sides of the pterygium meridian. After dried
      pooling of tears, topographic abnormalities returned, and the cornea became more
      uniform and symmetric. CONCLUSION: We conclude that the pooling of tears at the
      pterygium apex plays an important role, but fibrovascular traction has no effect
      on the corneal topographical changes induced by pterygium.

PMID- 12802350
TI  - Is screening with digital imaging using one retinal view adequate?
AB  - PURPOSE: To compare the detection of diabetic retinopathy from digital images
      with slit-lamp biomicroscopy, and to determine whether British Diabetic
      Association (BDA) screening criteria are attained (>80% sensitivity, >95%
      specificity, &<5% technical failure). METHODS: Diabetics referred for screening
      were studied in a prospective fashion. A single 45 degrees fundus image was
      obtained using the nonmydriatic digital camera. Each patient subsequently
      underwent slit-lamp biomicroscopy and diabetic retinopathy grading by a
      consultant ophthalmologist. Diabetic retinopathy and maculopathy was graded
      according to the Early Treatment of Diabetic Retinopathy Study. RESULTS: A total
      of 145 patients (288 eyes) were identified for screening. Of these, 26% of eyes
      had diabetic retinopathy, and eight eyes (3%) had sight-threatening diabetic
      retinopathy requiring treatment. The sensitivity for detection of any diabetic
      retinopathy was 38% and the specificity 95%. There was a 4% technical failure
      rate. There were 42/288 false negatives and 10/288 false positives. Of the 42
      false negatives, 18 represented diabetic maculopathy, 20 represented peripheral
      diabetic retinopathy and four eyes had both macular and peripheral changes. Three
      eyes in the false-negative group (1% of total eyes) had sight-threatening
      retinopathy. There was good concordance between the two consultants (79%
      agreement on slit-lamp biomicroscopy and 84% on digital image interpretation).
      CONCLUSION: The specificity value and technical failure rate compare favourably
      with BDA guidelines. The low sensitivity for detection of any retinopathy
      reflects failure to detect minimal maculopathy and retinopathy outside the 45
      degrees image. This could be improved by an additional nasal image and careful
      evaluation of macular images with a low threshold for slit-lamp biomicroscopy if
      image quality is poor.

PMID- 12802351
TI  - Visual perception during phacoemulsification cataract surgery under subtenons
      anaesthesia.
AB  - AIM: The aim of this study was to record the subjective visual experience of
      patients during phacoemulsification and intraocular lens implantation under
      subtenons anaesthesia. METHODS: Prospective, nonrandomised, cohort, postoperative
      questionnaire based study. Patients selected underwent routine
      phacoemulsification and intraocular lens implantation under regional subtenons
      anaesthesia. chi(2) and Fisher's exact tests (two-tail) were used to evaluate the
      data. RESULTS: A total of 104 patients were selected, 38 (36.5%) were male and 66
      (63.5%) were female. The mean age of patients was 74.0+/-8.8 years. In all, 87.5%
      saw light during the operation with 9.6% finding this painful. Photophobia was
      highest among younger patients (P=0.002). Coloured lights were seen by 56.7% and
      13.5% found the visual experience frightening. Frightening visual experiences
      were significantly associated with the perception of colour (P=0.005) and
      photophobia (P=0.003). A volume of anaesthetic greater than 4 m was associated
      with a significant reduction in anxiety as a result of the visual experience
      (P=0.003). None of the other visual phenomena recorded were associated with a
      frightening visual experience. CONCLUSIONS: Patients undergoing regional
      anaesthesia experience a wide variety of visual sensations during cataract
      surgery. Perception of colour and volumes of anaesthetic less than 4 m appear to
      be associated with the visual experience being more frightening. Detailed
      preoperative counselling is mandatory. It should include comprehensive
      information about visual perception during the procedure relieving the patients
      from unnecessary distress.

PMID- 12802352
TI  - Residual debris as a potential cause of postphacoemulsification endophthalmitis.
AB  - AIM: To examine residual debris within sterilised instruments prior to cataract
      surgery. METHODS: (i) Flushings from 32 sets of phacoemulsification instruments,
      sterilised according to hospital routine protocols, were taken preoperatively and
      analysed by scanning electron microscopy (SEM). (ii) A total of 16 sets of
      flushings from a different institute were collected-with separation of samples
      collected from phacoemulsification and those from irrigation-aspiration (IA)
      instruments-and analysed in the same way. (iii) A total of 15 sets of flushings
      were collected from instruments where an automated flushing system was used prior
      to sterilisation. RESULTS: (i)In the first study, 62% were clean, 16% were
      moderately contaminated and 22% were severely contaminated. Various contaminants
      were identified including lens capsule and cells, man-made fibres, squamous
      cells, bacteria, fungal elements, diatoms, red blood cells and proteinaceous
      material. (ii) In the second study, the results were similar and contamination of
      both phacoemulsification and IA instruments was shown. (iii) The third study
      showed that although a decrease in contamination followed automated flushing,
      contamination was not completely eliminated. CONCLUSIONS: Although all equipment
      had been sterilised, pyrogenic material was still present. These findings
      emphasise the importance of meticulous cleaning of all surgical equipment in
      which biological debris can remain.

PMID- 12802353
TI  - Intraocular lymphoma: a series of 14 patients with clinicopathological features
      and treatment outcomes.
AB  - AIMS: To assess the clinical features, pathology, mortality (systemic outcome)
      and ocular complications (visual outcome) of a cohort of patients treated for
      intraocular lymphoma. METHODS: Retrospective case analysis of medical records and
      review of pathology of a consecutive series of patients presenting with
      intraocular lymphoma in Melbourne over 11 years between 1990 and 2000.
      Categorical factors influencing survival were examined by the Kaplan-Meier
      estimator and groups compared with the log rank test. RESULTS: A total of 14
      patients were included. The median age of onset of symptoms was 62.5 years. Most
      were male (64%) and had bilateral eye involvement (64%). The commonest
      presentation was vitritis in 12 patients, with a median delay of 4 months before
      diagnosis. In all, 10 patients had B-cell lymphoma, three patients T-cell
      lymphoma and one null-cell. Four patients had prior systemic lymphoma. Eight
      patients had primary central nervous system non-Hodgkin's lymphoma (PCNSL).
      Treatment included combined radiation to the eye and chemotherapy in 10 patients.
      Complications of radiotherapy included cataract in five (50%), dry eyes in four
      (40%), punctate keratopathy in two (20%), radiation retinopathy in two (20%), and
      optic atrophy in one (10%). A total of 11 patients died of lymphoma (79%). One
      has residual ocular disease, while two have survived for more than 5 years from
      initial presentation. Although currently disease free, one of these has a poor
      visual outcome with acuity less than 6/60 secondary to ocular complications of
      treatment. CONCLUSIONS: Our study had 29% with prior systemic lymphoma, 57%
      associated with PCNSL and 14% with intraocular disease only. Overall survival is
      low (21%) and relapses common in those surviving beyond 12 months. Visual outcome
      in survivors is very poor due, in large part, to significant complications from
      radiotherapy.

PMID- 12802354
TI  - Central serous chorioretinopathy as a complication of postcardiac transplant
      corticosteroid therapy.

PMID- 12802355
TI  - Multifocal asymptomatic retinal pigment epithelial detachments in neurosyphilis.

PMID- 12802356
TI  - Spontaneous suprachoroidal haemorrhage associated with high myopia and aspirin.

PMID- 12802358
TI  - Lipogranuloma of the nasolacrimal system, an iatrogenic and preventable entity.

PMID- 12802357
TI  - Closure of cyclodialysis cleft using diode laser.

PMID- 12802359
TI  - The diagnosis of autosomal dominant late-onset retinal degeneration in two
      sisters.

PMID- 12802360
TI  - Ocular coloboma and radial aplasia: syndrome or association.

PMID- 12802361
TI  - Interferon-associated retinopathy.

PMID- 12802362
TI  - Intraepithelial sebaceous gland carcinoma with pagetoid spread presenting as
      marginal keratitis: a case report.

PMID- 12802363
TI  - Pubic lice effectively treated with Pilogel.

PMID- 12802364
TI  - Rapid bilateral sequential visual loss secondary to optic canal metastases in
      prostatic carcinomatosis.

PMID- 12802365
TI  - OCT vitreoretinal interface patterns.

PMID- 12802366
TI  - Acute posterior multifocal placoid pigment epitheliopathy associated with
      adenovirus infection.

PMID- 12802367
TI  - Homonymous hemianopia and driving.

PMID- 12802369
TI  - Congenital nasolacrimal duct obstruction requiring external
      dacryocystorhinostomies in a child with foetal valproate syndrome.

PMID- 12802370
TI  - Primary retinal detachment surgery.

PMID- 12802371
TI  - The association between the use of tourniquet during operation and the
      development of pulmonary thromboembolism and deep vein thrombosis.

PMID- 12802372
TI  - [Management of regular exercise in pregnant women].
AB  - In recent years with ever-increasing numbers of pregnant women wanting to
      participate in sport activities, the question as to how safe maternal exercise is
      for mother and fetus has become more important. The effects of pregnancy on
      maternal cardio-respiratory system include increases in oxygen consumption,
      cardiac output, heart rate, stroke volume, and plasma volume. The increase in
      oxygen reserve seen in early pregnancy is reduced later, suggesting that maternal
      exercise may present a greater physiological stress in the third trimester. The
      aims of this article are 1) to comment on the evidence relating to the health
      risks and benefits of physical activity for pregnant women and their unborn
      fetuses and 2) to realize guidelines for management of maternal exercise. In the
      absence of either obstetric or medical complications, pregnant women can continue
      to exercise and derive related benefits. The type, intensity, frequency, and
      duration of the exercise seem to be important determinants of its beneficial
      effects. Evidence suggests that weight-bearing exercise produces a greater
      decrease in oxygen reserve than non weight-bearing exercise. Furthermore, to
      maintain a heart rate below 150 beats per minute during pregnancy, the intensity
      of weight-bearing exercise must be reduced. In addition, depending on the
      individual's needs and the physiologic changes associated with pregnancy, women
      may have to modify their specific exercise regimens. Although increases in the
      frequency of uterine contractions have been observed during physical activities,
      changes are often minimal. In response to moderate exercise, the increase in
      frequency of uterine contractions is gestation dependent and significant in the
      third but not in the second trimester. The physiological adaptations to exercise
      during pregnancy appear to protect the fetus from potential harm and, while an
      upper level of safe activity has not been established, the benefits of continuing
      to be active during pregnancy appear to outweigh any potential risks. All
      decisions about participation in physical activity during pregnancy should
      however be made by women in consultation with their medical advisers.

PMID- 12802373
TI  - Evaluation of the neurotoxicity of paclitaxel and carboplatin by current
      perception threshold in ovarian cancer patients.
AB  - OBJECTIVES: Combination chemotherapy consisting of paclitaxel and carboplatin has
      recently started to be given as the regimen of first choice for epithelial
      ovarian cancer. One of its side effects, however, is neurotoxicity, and this
      neurotoxicity has been reported to be the dose-limiting factor. Since it is
      necessary to measure the severity of the neurotoxicity objectively and
      quantitatively, we evaluated it on the basis of current perception threshold
      (CPT) values, which is easy and non-invasive. METHOD: Sixteen patients with
      epithelial ovarian cancer were given paclitaxel (175 mg/m(2), 3 hours) and
      carboplatin (area under the curve of 5) every three weeks, and the CPT values
      were measured at two sites on the day before and several times after
      administration. RESULTS: All patients exhibited mild neurotoxicity, but it was
      never so severe that chemotherapy could not be continued. The CPT values peaked
      on day 4 during one course of chemotherapy, but decreased thereafter and returned
      almost to the baseline by three weeks, in the same way as the patients'
      complaints. The CPT values decreased with the number of courses, and patients'
      complaints gradually increased. The CPT values increased more in the cases
      previously treated with cisplatin than in the other cases. These changes were
      seen at 2,000 Hz, which generally corresponds to large, myelinated nerves.
      CONCLUSION: There were correlations between the changes in the patients' CPT
      values and their degree of neurotoxicity. We expect to be able to predict severe
      neurotoxicity and evaluate the effect of drug therapy for neurotoxicity by
      measuring CPT values.

PMID- 12802374
TI  - Is transvaginal ultrasonography at mid-trimester useful for predicting early
      spontaneous preterm birth?
AB  - Numerous reports have examined the relationship between sonographically
      determined cervical length and spontaneous preterm birth. Moreover, large
      screening studies have consistently demonstrated that the shorter the cervical
      length, the higher the rate of spontaneous preterm delivery. However, the
      sensitivity and positive predictive value of the cervical length for detecting
      preterm birth were low. Subsequently, we developed a new sonographic parameter
      termed "cervical gland area (CGA)". The purpose of this study was to determine
      whether sonographic cervical findings (shortened cervical length or absence of
      CGA) at 16 - 19 weeks' gestation could predict spontaneous preterm birth. The
      absence of CGA as compared to the shortened cervical length showed a higher
      sensitivity (75.0% vs. 50.0%) and a significantly elevated positive predictive
      value (54.5% vs. 8.3%) for preterm birth before 32 weeks' gestation. It was
      concluded that the absence of CGA was a novel and useful sonographic parameter
      for predicting early spontaneous preterm birth.

PMID- 12802375
TI  - Psychiatric intervention for Japanese Nationals in New York.
AB  - This study examined the characteristics of Japanese patients who required
      psychiatric intervention through the Consulate-General Japan in New York. The
      findings show that 61.5% of cases were tourists in contrast with 38.5% who were
      residents. Seventy three point one percent of all cases had psychiatric disorders
      prior to traveling to the United States. Seventy one point two had schizophrenia,
      and 48.1% required intervention within one week stay in the United States. The
      study indicated cultural elements had little influence on their psychiatric
      crises. The dominant cases, which were schizophrenics who traveled because of
      their delusional symptoms, were consistent with cases of "voyage pathologique".
      It was also suggested that cases with personality disorders are increasing in
      number. And we inferred that cases with substance-related disorders, particularly
      among young illegal residents, must be present in greater numbers.

PMID- 12802376
TI  - Fetal plasma prostaglandin F(2alpha) and cortisol responses to high-dose
      endotoxin administration in fetal goats.
AB  - Intrauterine inflammation/infection has been associated with prenatal mortality
      and morbidity. However, few studies have been performed to investigate how the
      fetus responds to intrauterine inflammation/infection in utero. In the present
      study, fetal plasma prostaglandin (PG) F(2alpha) and cortisol responses to high
      dose fetal endotoxin administration were evaluated in late gestation goats (n=8).
      After 160 microg/kg of fetal weight of endotoxin (Escherichia coli, O111:B4
      lipopolysaccharide) administration via the fetal jugular vein over a 5-min
      period, fetal plasma PGF(2alpha) and cortisol levels, fetal blood gases and pH
      were measured periodically. After endotoxin administration, fetal plasma cortisol
      levels significantly increased to 9.5+/-0.8 ng/mL and 9.3+/-0.7 ng/mL after 1 and
      3h, respectively (p<0.05) and plasma PGF(2alpha) levels did not change throughout
      the study. These results suggest that absent PGF(2alpha) and attenuated cortisol
      responses to high-dose fetal endotoxin administration, relative to the adult, may
      be a self-protective mechanism that diminishes premature delivery and fetal
      asphyxia.

PMID- 12802377
TI  - Coronary artery bypass grafting without cardiopulmonary bypass: a five-year
      experience.
AB  - The current drive to practice less invasive surgery is changing surgical practice
      towards safer and simpler procedures. The practice of coronary artery bypass
      grafting (CABG) on a beating heart without cardiopulmonary bypass (CPB), off-pump
      CABG or OPCAB, has been gaining great attention as an alternative approach to
      conventional CABG. Since the first adoption of OPCAB in 1997 at our department,
      181 patients have undergone OPCAB. OPCAB was indicated for patients who were
      possibly at risk for CPB, i.e., those who were elderly, who had a history of
      cerebrovascular disease, whose ascending aorta was severely atherosclerotic with
      calcification, whose respiratory function was compromised, or whose renal
      function was compromised. A patient with a concomitant malignant neoplastic
      disorder was also a candidate for OPCAB because of the possible deleterious
      effect of CPB on the immune system. More recently, when the coronary anatomy was
      suitable for OPCAB, even in younger or less risky patients, OPCAB was indicated.
      The OPCAB procedure was performed through a median sternotomy in 146 patients
      (80.6%), a left thoracotomy in 27 (14.9%), a subxiphoid approach in 6 and a
      combined one in 2. One hundred and eleven patients (61.3%) received 1 or 2 grafts
      (Group I) and 70 (38.7%) received 3 or more grafts (Group II). The number of
      grafted vessels in Group II patients was 3 to 5 with a mean of 3.44. The mean
      operative time was 163 minutes in Group I and 209.5 minutes in Group II. The
      frequency of the use of arterial grafts such as LITA, RITA and RA was
      significantly higher in Group II than in Group I. Death occurred in 3 patients
      with acute coronary syndrome who had to undergo urgent surgery. Angiographic
      examination was performed within 3 months, postoperatively, in 98 patients
      (54.1%) revealing the overall patency rate of each graft: LITA82/83 (98.8%), RITA
      33/33 (100%), GEA 15/16 (93.8%), RA 20/20 (100%), and SVG 15/16 (93.8%). We
      conclude that, in light of our 5-year experience, off-pump CABG on a beating
      heart can be safely and effectively performed, with acceptable angiographic
      results even in patients with multi-vessel coronary disease requiring multiple
      revascularization. This procedure enables us to perform successful coronary
      bypass surgery for those who otherwise would not have been candidates for
      conventional CABG.

PMID- 12802378
TI  - Effects of maternal oxygen supplementation on fetal oxygenation and lipid
      peroxidation following a single umbilical cord occlusion in fetal goats.
AB  - Maternal oxygen supplementation is commonly performed to improve fetal
      oxygenation and acid-base balance during fetal asphyxia. The efficiency of this
      treatment is controversial, which may be associated with the production of oxygen
      free radicals and lipid peroxidation. However, only a few studies have been
      performed to evaluate these issues. To clarify them, we investigated the effects
      of maternal oxygen supplementation on fetal oxygenation and lipid peroxidation
      following fetal asphyxia in late gestation goats. We measured fetal blood gases,
      pH and plasma malondialdehyde (MDA), one of the endproducts of lipid
      peroxidation, before, during and after fetal asphyxia with and without maternal
      oxygenation in late gestation goats. Fetal asphyxia was induced by a single total
      umbilical cord occlusion of 3 minutes' duration, and maternal oxygenation was
      initiated at 20 min before the cord occlusion and terminated at 20 min after the
      release of cord occlusion. Maternal oxygen supplementation resulted in a
      significant increase in fetal PaO(2) before and after the cord occlusion
      (p<0.05). During the cord occlusion, the extents of hypoxia and acidemia were not
      changed by maternal oxygen supplementation. Fetal plasma MDA levels before
      maternal oxygen supplementation averaged 0.80+/-0.04 micromol/L, significantly
      increased after the initiation of maternal oxygen supplementation (1.11+/-0.07
      micromol/L), and further increased following fetal asphyxia (1.28+/-0.06
      micromol/L), and after the release of the cord occlusion (1.58+/-0.7
      micromol/L)(p<0.05). These values were significantly higher than those in fetuses
      without oxygenation. We conclude that maternal oxygen supplementation increased
      fetal oxygenation but caused a concomitant increase in lipid peroxidation in the
      fetus.

PMID- 12802379
TI  - Characteristic prenatal ultrasonographic findings of patent urachus: a case
      report.
AB  - A characteristic prenatal ultrasonographic finding of patent urachus is
      described. Routine obstetrical ultrasonography first revealed a cystic mass in
      the umbilical cord at 16 weeks of gestation. The mass spontaneously decreased in
      size and was undetectable at full term on serial ultrasound examination. The male
      newborn infant was delivered uneventfully at 38 weeks of gestation, weighing
      2,774 g. He was noted to void urine from the umbilicus soon after birth, and the
      diagnosis of patent urachus was confirmed. On the 8th day of life, complete
      surgical removal of the urachus was performed, and the postoperative course was
      uneventful. An umbilical cystic mass which diminishes in size over the course of
      pregnancy is a sugesstive prenatal sonographic finding for urachal anomalies.

PMID- 12802380
TI  - The longitudinal course of two cases with cretinism diagnosed after adolescence.
AB  - In Japan, mass screening tests on newborns for Cretinism have been performed
      since 1984, Cretinism is a very rare condition. We report the clinical course and
      complications of longitudinal thyroid hormone replacement therapy (liothyronine
      sodium: T3) of two women with Cretinism and ectopic thyroid gland for the past 33
      years until 2001. They were born in April 1951 (Case 1) and in January 1952 (Case
      2). On admission in June 1968, they were 17 and 16 years old. They had short
      stature, mental retardation, macroglossia, saddle nose, retardation of bone
      maturation, edematous face, coexistence of permanent teeth and deciduous teeth,
      abdominal distention, hypotonia, anemia, hypophosphatemia and
      hypercholesterolemia. After admission, Case 2 had an appendectomy for
      appendicitis. She was found to have a right ovarian cyst, but was not operated
      upon. Later, the right ovarian cyst disappeared during thyroid hormone
      replacement therapy. The complication in this case was NIDDM. Over secretion of
      thyroid hormone in for example, hyperthyroidism sometimes induces NIDDM. On their
      admission, a levothyroxine sodium (T4: Thyradin S) was unavailable in Japan, so
      we had no choice but to treat them with liothyronine sodium for thyroid hormone
      replacement therapy. We suspect that liothyronine sodium replacement therapy
      probably induced NIDDM. They experienced improved bone maturation, anemia,
      hypophsphatemia and hypercholesterolemia, but their intellectual and mental
      disabilities were not improved.

PMID- 12802381
TI  - One-step insertion of an expandable metallic stent for unresectable common bile
      duct carcinoma.
AB  - BACKGROUND: This report describes a one-step insertion of an expandable metallic
      stent to treat obstructive jaundice due to unresectable common bile duct
      carcinoma. METHODS: A percutaneous transhepatic cholangiogram is obtained, and
      the bile duct obstruction is negotiated with a guide wire. After advancing the
      catheter into the duodenum, contrast material is injected to measure the length
      of the stenosis. After an expandable metallic stent is positioned, an external
      biliary drainage catheter is left in place to provide temporary drainage. The
      catheter is removed after stent patency is confirmed after 3 days. CONCLUSIONS:
      One-step insertion of an expandable metallic stent for biliary obstruction is a
      useful method that shortens hospitalization. Once it has been decided to use
      stent palliation, the stent should be inserted without undue delay to maximize
      symptomatic relief and cost benefits.

PMID- 12802382
TI  - [The present status of nutritional therapy after gastrectomy according to the
      commentary for the guideline of gastric cancer therapy].

PMID- 12802383
TI  - [A case of multicentric bronchio-alveolar cell carcinomas with mild improvement
      during clinical course].
AB  - It is very important for clinicians to recognize that some lung cancers,
      especially among the bronchiolo-alveolar cell carcinomas (BAC), rarely show mild
      improvement in opacity during the clinical course. We would like to present a 63
      year-old woman who demonstrated very unusual exacerbation and improvement in lung
      opacity during 7 years of follows up. The abnormal chest shadows pointed out in
      an initial screening checkup and in a following chest CT presented 4 nodules in
      both lung fields; 2 of them appeared to have cavities. One of these nodules
      showed a definitely reduced size in a chest CT taken after one year of follow up
      study. We therefore determined it was probably not malignant of this time. But,
      after seven years the patient revisited our institute complaining of
      bronchorrhea. The chest CT taken immediately revealed increased size of each
      nodule and progression to pulmonary consolidation of the right lower lobe. A
      transebroncheal biopsy led to a diagnosis of bronchiolo-alveolar cell carcinoma
      pathologically. The incidence of BAC has recently shown a remarkable increase and
      radiological images of these tumors are various. It is important, therefore, to
      consider the possibility of BAC for differential diagnose of cases presenting
      abnormal pulmonary shadows.

PMID- 12802385
TI  - Age-related changes in electrical reactions of rat aorta endothelium elicited by
      acetylcholine and ATP.
AB  - Age-related changes in some electrophysiological parameters of the endothelium in
      isolated rat aorta were studied. In comparison with young rats (6 months),
      resting potential of the endothelium in aged rats (24-26 months) was
      significantly higher and varied in a wider range. The electrical responses of
      intact endothelium of isolated aorta to acetylcholine were typical and regular in
      young rats, while in aged rats these responses were irregular and atypical. It is
      hypothesized that atypical electrical responses of the endothelium to
      acetylcholine and ATP in aged animals result from functional clustering
      associated with disturbances in electrical contacts between endotheliocytes. We
      hypothesize that the age-related decrease in NO production is related to
      disturbances of electrical properties of endothelial membrane.

PMID- 12802384
TI  - Gaseous superoxide potentiation of the effect of nonnarcotic analgesics in low
      doses.
AB  - The action of inhalation of gaseous superoxide on the effects of low doses of
      nonnarcotic analgesics was studied on volunteers in the little finger compression
      test. After administration of placebo, inhalation of gaseous superoxide produced
      a negligible transient decrease in pain tolerance threshold. Inhalation of
      gaseous superoxide potentiated the effects of threshold doses of novalgin and
      aspirin and prolonged their action, but did not modulate the analgesic effect of
      diclofenac. It is assumed that the potentiating effect of superoxide on the
      action of analgesics is related to inhibition of monoamine oxidases leading to
      accumulation of monoamines in the brain.

PMID- 12802386
TI  - Mechanisms of adaptation to flow reactions in rats after systemic blood arrest.
AB  - The rats survived 10- or 15-min systemic blood flow arrest were exposed to
      various extreme factors within the following 2 months. It was found that the
      processes leading to functional isolation of CNS play a protective role: they
      moderate behavioral response to acute stress and alleviate the degree of neuron
      damage induced by long-term stress during acquisition of a complex food-procuring
      reflex.

PMID- 12802387
TI  - Peculiarities of the development of analgesic effect during transcutaneous
      dynamic electrical stimulation.
AB  - The effect of transcutaneous dynamic electrical neurostimulation on the
      development of analgesia was studied in behavioral and electrophysiological
      experiments on rats. A 30-min dynamic electrical stimulation elevated the
      nociception threshold in tail-flick and hot plate tests, increased the threshold
      of the late nociceptive flexor reflex, and decreased the number of bursts in the
      response. Intraperitoneal injection of naloxone (2 mg/kg) abolished the analgesic
      effect of dynamic electrical neurostimulation. It is concluded that the key role
      in reflex analgesia during dynamic electrical neurostimulation is played by the
      endogenous cerebral opioid system, which inhibits the nociceptive signals
      traveling to CNS via unmyelinated C-fiber afferents.

PMID- 12802388
TI  - Stress-limiting effect of dehydroepiandrosterone sulfate and its mechanism.
AB  - Dehydroepiandrosterone sulfate prevented the increase in corticosterone level in
      rats induced by repeated exposure to stress. The mu-opioid receptor blocker
      naltrexone administered in a dose of 0.1 mg/kg 20 min before treatment with
      dehydroepiandrosterone sulfate abolished the effect of this agent.
      Dehydroepiandrosterone sulfate and naltrexone had no effect on rats after acute
      stress.

PMID- 12802389
TI  - Effects of dynorphin A(1-13) on DNA synthesis and free radical oxidation in
      respiratory organs of newborn albino rats pretreated with NG-nitro-L-arginine
      methyl ester.
AB  - Dynorphin A(1-13) increased the number of DNA-synthesizing epitheliocytes in the
      bronchi and inhibited free radical oxidation in the lungs of newborn albino rats.
      Pretreatment with NG-nitro-L-arginine methyl ester not only abolished, but also
      reversed the effect of this peptide.

PMID- 12802390
TI  - Effects of central endothelin-1 in normotensive and spontaneously hypertensive
      rats.
AB  - Changes in blood pressure and sympathetic nerve activity induced by local
      injection of endothelin-1 into the rostroventrolateral medulla were studied in
      narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive
      WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a
      transient increase in blood pressure and sympathetic nerve activity followed by
      progressive hypotension and bradycardia. Pretreatment with ETB-receptor
      antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while
      pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1
      abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor
      blockade was most effective in normotensive rats. Our findings suggest that
      cardiovascular disorders in SHRSP rats can be related to peculiarities in the
      rostroventrolateral medullar endothelin system.

PMID- 12802391
TI  - Nitric oxide and HSP70 proteins during normal pregnancy, gestosis, and
      preclinical gestosis.
AB  - We measured the content of NO metabolites in blood plasma and urine and
      concentration of HSP70 proteins in the plasma and leukocytes from 126 women with
      normal pregnancy, gestosis, and preclinical gestosis. In women with gestosis
      accompanied by NO deficiency the concentration of HSP70 proteins in the plasma
      increased more significantly than in leukocytes. These changes are an important
      marker of endothelial dysfunction and reflect the severity of cell damage during
      this disorder. The decrease in excretion of NO in the urine and increase in HSP70
      protein content in leukocytes and plasma characterize endothelial dysfunction in
      women with preclinical gestosis.

PMID- 12802392
TI  - Desynchronosis and erosive and ulcerative lesions of the stomach in rats active
      or passive in the open-field test: effect of exogenous melatonin.
AB  - We studied the effect of a phase shift in circadian rhythms (desynchronosis) on
      the development of erosive and ulcerative lesions in the gastric mucosa in male
      Wistar rats with different behavioral activity in the open-field test. The
      animals kept under conditions of natural or shifted light-dark cycle were
      untreated or intraperitoneally received physiological saline (1 ml) and melatonin
      (1 or 2 mg/kg). Desynchronosis induced gastric ulcers in active rats not
      receiving injections or intraperitoneally injected with physiological saline. No
      gastric ulcers were found in passive animals kept under shifted light-dark cycle.
      Melatonin induced gastric ulcers in passive animals kept under natural light-dark
      cycle. Gastric ulcers were not found in active rats subjected to desynchronosis
      and receiving melatonin. Our results indicate that treatment with melatonin for
      the correction of changes induced by shifts in the light-dark cycle should be
      performed taking into account individual behavioral characteristics.

PMID- 12802393
TI  - Changes in DNA synthesis and morphometric indexes of the myocardium in albino
      rats treated with angiotensin II.
AB  - Autoradiography with 3H-thymidine showed that angiotensin II injected
      intraperitoneally to newborn albino rats from the 2nd to 6th day of life
      stimulates DNA synthesis in the myocardium of the left ventricle and increased
      the area of cardiomyocytes and number and area of nucleoli. Two weeks after
      treatment the area of cardiomyocytes and the number of nucleoli increased, while
      the count of PCNA-positive nuclei remained unchanged. Immunohistochemical assay
      for vimentin showed that the ratio between the number of cardiomyocytes and
      connective tissue cells remained unchanged. In 45-day-old rats (38 days after
      treatment) the intensity of DNA synthesis and morphometric indexes of the
      myocardium did not differ from the control. Fivefold treatment of adult rats with
      angiotensin II increased the number and area of nucleoli, but had no effect on
      the count of connective tissue cells.

PMID- 12802394
TI  - Structure of C-reactive protein excreted in urine during acute rejection
      episodes.
AB  - During acute rejection of renal allografts C-reactive protein is excreted in
      urine in a monomeric form. We developed an immunochemical method for detecting
      monomeric C-reactive protein in human physiological fluids, which is based on
      latex agglutination.

PMID- 12802396
TI  - Riboflavin content in male spermoplasm.
AB  - Riboflavin concentration in male spermoplasm depends on consumption of vitamin B2
      and is 3-50 times higher than in the blood plasma, depending on the riboflavin
      status. Normal levels of riboflavin content in the spermoplasm were evaluated by
      investigating the metabolic relationship between riboflavin concentration in the
      spermoplasm and blood plasma and the relationship between riboflavin saturation
      of the spermoplasm and the duration of treatment with vitamin B2. Both methods
      yielded close values: 60-130 and 85-96 ng/ml, hence, 80 ng/ml can be taken for
      the lower normal threshold level of riboflavin in the spermoplasm.

PMID- 12802395
TI  - Dual effects of endogenous DNases on transcriptionally active and inactive
      chromatin.
AB  - Experiments on resting hepatocytes with inactive c-fos gene and active albumin
      gene. We revealed that DNA of the transcribed gene is less susceptible to the
      influence of endogenous Ca2+/Mg(2+)-dependent DNases in matrix-associated and
      highly soluble chromatin fractions. In the fraction of low soluble chromatin
      active gene was more accessible for DNases. Our results indicate that activity of
      endogenous DNases can change in the transcribed gene locus.

PMID- 12802397
TI  - Antimutagenic and antioxidant activities of crown compounds in comparison with
      the effects of garlic extract.
AB  - Antimutagenic activity of N-carboxyalkyl derivatives of aza- and benzoazacrown
      compounds was revealed and antimutagenic activity of garlic extract was
      confirmed. Specific genoprotective effect of crown compounds towards the effects
      of various mutagens was demonstrated. The antimutagenic effect of these compounds
      was not realized via antioxidant mechanisms, while the protective effect of
      garlic extract was associated with its antioxidant and reparative activities.

PMID- 12802398
TI  - Effect of amiodarone on the dynamics of mechanical restitution of rat papillary
      muscles.
AB  - We studied the effect of amiodarone (class III antiarrhythmic drug) on the
      dynamics of mechanical restitution of rat papillary muscle. Amiodarone produced a
      weak negative inotropic effect and stimulated potentiation of contractility of
      the muscle preparation after short-term (4-60 sec) cessation of its electrical
      stimulation. On the other hand, the time of attaining half-maximum amplitude of
      contractions after amiodarone treatment did not differ from the control. Analysis
      of curves presenting the drop of potentiation of muscle preparation contractility
      after resumption of regular electrical stimulation after 60-sec arrest until
      attaining a stable level showed that the amplitude returned to the initial level
      by the 9thcontraction-relaxation cycle both in the control and after amiodarone
      treatment. Coefficient of the drop of contraction amplitude potentiation was
      virtually the same in the two groups. Presumably, amiodarone does not modulate
      calcium-binding capacity of the sarcoplasmic reticulum, but improves Ca retention
      in the sarcoplasmic reticulum stores.

PMID- 12802399
TI  - Effect of Semax peptide on survival of cultured rat pheochromocytoma cells during
      oxidative stress.
AB  - We studied the effects of Semax (antiinsulin peptide with neuroprotective effect)
      on the survival of cultured rat pheochromocytoma cell after oxidative stress
      induced by short-term incubation with hydrogen peroxide. Studies with fluorescent
      dyes propidium iodide and Hoechst 33258 showed that cell incubation with hydrogen
      peroxide led to the formation of damaged cells with characteristic signs of
      necrosis. Semax dose-dependently reduced the number of cells damaged by oxidative
      stress. The efficiency of Semax depended on the time of its addition to the
      culture medium. The results suggest that the neuroprotective effect of Semax in
      ischemic stroke can be due to its capacity to protect neurons from damage caused
      by oxidative stress.

PMID- 12802400
TI  - Location and intensity of IL-8 and TGF-beta2 mRNA production in the fimbrial
      compartment of fallopian tubes and IL-10 in the endometrium in patients with
      pyoinflammatory adnexal diseases.
AB  - The location and level of IL-8 and TGF-beta2 expression in the fimbrial
      compartment of fallopian tubes and IL-10 expression in the endometrium of women
      with pyoinflammatory adnexal diseases were studied by in situ hybridization.
      These diseases are associated with considerable changes in the levels of local
      production of these cytokines. Inflammatory infiltration and epithelial cells
      were most active producers of IL-9 and TGF-beta2 in the fimbrial compartment of
      fallopian tubes, while in the endometrium IL-10 gene was expressed at a high
      level primarily in the glandular epithelial cells.

PMID- 12802401
TI  - Study of Candida albicans strains isolated from women with various forms of
      vaginal candidiasis.
AB  - Adhesive activity of Candida albicans towards vaginal epitheliocytes is hormone
      dependent. Two types of C. albicans adhesins sensitive to polyphenyloxidase and
      asparaginase were detected. Laser irradiation nonspecifically modulated both
      adhesin types. Population relationships between fungi and lactobacilli in
      patients with vaginal candidal infection and in C. albicans carriers were
      studied. Genodiagnostic method for identification of C. albicans and
      morphogenesis-associated genes of these yeast-like fungi was approved.

PMID- 12802402
TI  - Delayed effect of antileukemic polychemotherapy on cell death and proliferation
      during remission of acute lymphoblastic leukemia in children.
AB  - The effect of programmed antileukemic drug therapy on cells of the tumor clone is
      not selective, and the drugs affect also intact bone marrow and peripheral blood
      cells. The cytotoxic effect of antitumor therapy is attained through triggering
      apoptosis and does not depend on the type of drug therapy. The treatment induces
      long-lasting changes in spontaneous cell death processes. The disturbances in the
      kinetics of cell death caused by drug therapy are compensated by changes in
      proliferative activity of bone marrow cells.

PMID- 12802403
TI  - Dynamics of precursor cell composition in bone marrow culture derived from mice
      deficient by tumor necrosis factor.
AB  - Hemopoiesis in a long-term bone marrow culture derived from mice deficient for
      tumor necrosis factor was maintained for more than 130 weeks, which was 4 times
      longer than in cultures from wild type mice. The dynamics of hemopoietic
      precursor cells of different maturity was studied in the suspension fraction of
      the culture. The incidence of granulocyt-macrophage precursor cells and cell
      forming cobblestone areas was studied by the method of limiting dilutions in
      culture. In contrast to cultures derived from wild type mice, in long-term bone
      marrow culture derived from tumor necrosis factor deficient mice, first, the
      incidence of early precursor cells gradually increased and then the incidence of
      all precursor cells sharply increased.

PMID- 12802405
TI  - Morphofunctional characteristics of antigen-presenting cells in lymph node in
      mice with experimental West Nile fever.
AB  - Pronounced transformation of cells in mesenteric lymph nodes, mainly in the
      thymus-independent zone and sinuses, was detected in albino mice experimentally
      infected with West Nile fever (strain 986). Maximum antigen-presenting activity
      was exhibited by activated macrophages, minimum activity--by dendritic cells of
      lymphoid follicles.

PMID- 12802404
TI  - Phenobarbital modifies antitumor effect of cyclophosphamide depending on the type
      of tumor cell death caused by it.
AB  - Antitumor effect of cyclophosphamide on LS and P388 tumors is realized via
      apoptosis and on HA-1 and Krebs-2 tumors resistant to apoptosis via necrosis of
      tumor cells. Phenobarbital induction of cyclophosphamide-metabolizing enzymes
      decreases and cimetidine inhibition potentiates the effect of cyclophosphamide on
      LS and P388 cells and does not modulate the effect on HA-1 and Krebs-2 cells.
      Presumably, apoptosis and necrosis of tumor cell are induced by different
      cyclophosphamide metabolites.

PMID- 12802406
TI  - Is replication of hepatitis C virus a marker of activity of infectious process?
      (Findings of polymerase chain reaction and morphological analysis of liver biopsy
      specimens).
AB  - Comparative study of replication markers of hepatitis C virus in various
      biological substrates and evaluation of activity of chronic HCV infection in
      liver biopsy specimens showed that replication of hepatitis C virus and the
      number of HCV-infected hepatocytes did not promote liver damage in chronic
      hepatitis C. These findings indicate that the expression of antiviral reactions
      by liver parenchyma cells plays the key role in the morphogenesis of HCV
      infection.

PMID- 12802407
TI  - Constitution and anthropometric parameters in indigenous population of Southern
      Altai Mountains.
AB  - Analysis of anthropometric parameters of 645 indigenous residents of Southern
      Altai Mountains belonging to two subethnic groups (165 Telengites and 480 Altai
      Kizhi) revealed constitutional characteristics distinguishing these groups from
      each other and from Europeans. Differences in body length and weight,
      distribution by constitution types, sexual dimorphism, and AB0 blood groups were
      detected. The specific features of constitution together with environmental
      factors can determine predisposition of individuals belonging of these subethnic
      groups to some diseases.

PMID- 12802408
TI  - Morphometric characteristics of liver acini in dogs with acute cholecystitis.
AB  - Morphometric analysis of the liver in dogs with acute cholecystitis revealed
      specific alterations in liver acini in various forms of acute cholecystitis.

PMID- 12802409
TI  - Experimental validation of videoendoscopic isolation and occlusion of the
      bloodflow in open ductus arteriosus.
AB  - The potentialities of videoendoscopic isolation and extravasal occlusion of large
      vessels with titanium clips were studied in acute and chronic experiments on 36
      animals and anatomic studies on 5 human cadavers. The number and optimal sites
      for insertion of trocars and disposition of instruments and thoracoscope for
      isolation of open ductus arteriosus were determined. A method for videoendoscopic
      isolation of vessels is developed and possible complications and measures for
      their liquidation evaluated. High efficiency and low traumatism of
      videoendoscopic operation are proven under condition of strict adherence to
      methodology and sufficient qualification of the surgeon in endosurgical
      manipulations.

PMID- 12802410
TI  - Genome of brain neurons in organization of systemic mechanisms of behavior.
AB  - Here we review the mechanisms underlying systemic regulation of the genome in
      brain nerve cells. Expression of early and late behavioral genes is regulated by
      systemic processes in dominant functional systems. The main elements of this
      molecular and genetic cascade are similar during learning and development.

PMID- 12802412
TI  - Effect of oxotremorine on resting membrane potential and cell volume in skeletal
      muscle fibers in rats after in vivo blockade of NO-synthase.
AB  - Denervation of rat phrenic muscle or block of NO-synthase in vivo increased the
      cross-section area of muscle fibers and decreased membrane resting potential.
      Oxotremorine prevented the development of denervation-induced or denervation-like
      (i.e. induced by NO-synthase blockade) membrane depolarization and increase of
      the cross-sectional area of muscle fibers. Pirenzepine abolished the effects of
      oxotremorine. It was concluded that non-quantal acetylcholine can be involved in
      the regulation of skeletal muscle fiber volume via activation of M1 muscarinic
      receptors followed by NO synthesis.

PMID- 12802411
TI  - Effect of antibodies to morphine on synaptic plasticity of the hippocampus.
AB  - Incubation of hippocampal slices with antibodies to morphine did not change the
      total excitatory postsynaptic potential of mossy fibers, but markedly facilitated
      long-term posttetanic potentiation. Culturing of the organotypic hippocampal
      culture in the presence of 10 microM morphine increased the total excitatory
      postsynaptic potential of mossy fibers and reduced the probability of long-term
      posttetanic potentiation.

PMID- 12802413
TI  - Antiapoptotic effect of heat adaptation in cultured cells.
AB  - Heat adaptation of cultured rat cardiomyoblasts and mouse myoblasts protected
      these cells from damage produced by staurosporine and attenuated metabolic
      disturbances. Heat adaptation inhibited apoptotic, but not necrotic cell death.
      The mechanism of antiapoptotic adaptive protection was not associated with
      prevention of mitochondrial depolarization, because heat adaptation not only
      induced depolarization of mitochondria, but also intensified this process under
      conditions of staurosporine-induced damage.

PMID- 12802414
TI  - Direct and cross-protective effects of heat adaptation in cultured cells.
AB  - The model of 6-day dosed heat adaptation was developed on cultured rat H9c2
      cardiomyoblasts and mouse C2c12 myoblasts. Heat adaptation produced a direct
      protective effect and increased the resistance of cells to heat shock. The cross
      protective effect of heat adaptation was manifested in an increase in the
      resistance to staurosporine-induced damage. Heat adaptation did not protect cells
      from oxidative damage. As differentiated from adaptation of the organism, heat
      adaptation produces direct and cross-protective effects that develop due to the
      action of environmental factors in the absence of neurohumoral agents. It should
      be emphasized that the cross-protective effect of heat adaptation in cultured
      cells is specific to a certain type of damage.

PMID- 12802415
TI  - Protective effect of carnosine on Cu,Zn-superoxide dismutase during impaired
      oxidative metabolism in the brain in vivo.
AB  - Natural hydrophilic antioxidant carnosine protects cerebral cytosolic Cu,Zn
      superoxide dismutase (SOD) under conditions of oxidative stress in various in
      vivo models: short-term hypobaric hypoxia in rats and accumulation of age-related
      changes in senescence-accelerated mice (SAMP). Administration of carnosine
      preventing Cu,Zn-SOD inactivation reduced mortality in rats and prolonged average
      life span in SAMP-mice.

PMID- 12802416
TI  - Use of HLDF-6 peptide for correction of disturbances in the endogenous opioid
      system in offspring of morphine-tolerant animals.
AB  - We studied the effect of bioactive peptide HLDF-6 on functional activity of the
      endogenous antinociceptive system in the offspring of morphine-tolerant animals.
      Disturbances in this system included changes in the thermonociceptive threshold
      and enkephalinase A activity in various brain structures. The peptide acted as a
      potent regulator of the homeostasis in systems responsible for the synthesis and
      catabolism of endogenous opioids. HLDF-6 effectively corrected disorders of the
      endogenous antinociceptive system.

PMID- 12802417
TI  - Water status and LPO in rat tissues during massive blood loss and irradiation
      with He-Ne laser.
AB  - We revealed a relationship between water balance and LPO in the myocardium,
      liver, and blood plasma during massive blood loss and irradiation with He-Ne
      laser. Low-intensity laser irradiation of the plasma inhibits LPO and normalizes
      water balance in rat tissues during massive blood loss.

PMID- 12802418
TI  - The leading role of membrane Ca(2+)-ATPase in recovery of Ca(2+) homeostasis
      after glutamate shock.
AB  - Combined blockade of Na(+)/Ca(2+) exchange, Ca(2+) uptake by mitochondria and
      endoplasmic reticulum usually does not prevent recovery of the basal level of
      intracellular Ca(2+) after 1-min action of glutamate (100 microM) or K(+) (50
      mM). However, replacement of Ca(2+) with Ba(2+), which cannot be transported by
      Ca(2+)-ATPase, considerably delayed the decrease in intracellular Ba(2+) after
      its rise caused by glutamate or potassium application in all examined cells,
      which attest to an important role of Ca(2+)-ATPase in Ca(2+) extrusion after the
      action of glutamate or K(+).

PMID- 12802419
TI  - A complex of antioxidant vitamins effectively inhibits free-radical oxidation of
      LDL phospholipids in blood plasma and membrane structures of the liver and
      myocardium.
AB  - Antioxidant effect of a complex preparation including antioxidant vitamins C, E,
      provitamin A and selenium was studied on the model of Cu(2+)-initiated free
      radical oxidation of LDL isolated from human blood plasma. The antioxidant effect
      of combined administration of alpha-tocopherol+ascorbic acid and alpha
      tocopherol+beta-carotene is far more pronounced that the antioxidant effect of
      individual components of these cocktails. Moreover, in the model system the
      combined action of all antioxidant components completely inhibited free-radical
      oxidation of LDL. A 30-day course of peroral administration of antioxidant
      vitamin cocktail and selenium to rats pronouncedly enhanced the antioxidant
      potential of liver and completely suppressed free-radical processes in the
      myocardium. It is suggested that preparations containing antioxidant vitamins and
      selenium can be perspective for prevention and complex therapy of
      atherosclerosis.

PMID- 12802420
TI  - Macrophage-granulocyte colony-stimulating factor and fibroblast growth factor in
      the blood of patients with hyperlipoproteinemia.
AB  - Solid-phase ELISA revealed increased content of macrophage-granulocyte colony
      stimulating factor and basic fibroblast growth factor in the serum of
      hyperlipoproteinemic patients.

PMID- 12802421
TI  - Apoptosis in fimbriae of fallopian tubes and endometrium in pyoinflammatory
      adnexal diseases.
AB  - In patients with pyoinflammatory adnexal diseases moderate or intense DNA
      degradation was observed in the majority of epithelial, stromal, and inflammatory
      infiltration cell in inflammatory foci in the fimbrial compartment of fallopian
      tubes without signs of tissue destruction. Expression of TNFR1 gene increased 2.7
      fold and expression of Fas gene decreased 3.1-fold compared to intact
      endosalpinx, which indicates induction of apoptosis triggered by tumor necrosis
      factor-alpha and inhibition of the Fas-dependent pathway. No signs of apoptosis
      were detected in the endometrium. Generalized apoptosis in the fimbrial
      compartment of the tubes can be a mechanism limiting the inflammatory process.

PMID- 12802422
TI  - The state of the immune system in thyroidectomized rats.
AB  - Disorders in the immune system manifesting in decreased weight and cellularity of
      lymphoid organs, decreased count of large granular lymphocytes, suppression of
      the immune response and metabolic activity of macrophages were observed in
      experimental animals 1-6 months after thyroidectomy. The intensity of these
      disorders depends on the period elapsed after the surgery. These disorders can
      result from not only changes in the levels of the pituitary-thyroid hormones, but
      also disturbances in the endocrine function of the thymus in thyroidectomized
      animals.

PMID- 12802423
TI  - Cow milk angiogenin induces cytokine production in human blood leukocytes.
AB  - Angiogenin isolated from cow milk induces the production of cytokines IL-1beta,
      IL-6, and TNF-alpha in human leukocytes; the level of production of each cytokine
      depends on the concentration of the preparation, and the dynamics of production
      depends on the time from the beginning of induction. Simultaneous treatment with
      angiogenin and phytohemagglutinin had an additive effect on the production of
      cytokines, the time of this effect manifestation being individual for each
      cytokine.

PMID- 12802424
TI  - Characteristics of interphase chromatin in hippocampal neurons in rats with
      different excitability of the nervous system exposed to stress at different time
      of the day.
AB  - The structural (number and area of chromocenters) and optical (relative optical
      density of chromocenters) characteristics of condensed chromatin in hippocampal
      CA3 neurons in rats differing by excitability of the nervous system (intact and
      exposed to short-term emotional painful stress) depended on the time of the day
      and genotypical characteristics of the experimental animals. The detected changes
      were independent, which attests to specificity of mechanisms determining these
      features and/or can be attributed to structural and functional heterogeneity of
      condensed chromatin (heterochromatin, euchromatin, etc.).

PMID- 12802425
TI  - Lentivirus vector can integrate in the genome and exist and replicate in the cell
      as an episome.
AB  - Lethally irradiated mice were reconstituted with few purified primitive
      hemopoietic stem cells containing sequences of a gene encoding green fluorescent
      protein. The gene was transferred using a lentivirus vector. The presence of the
      marker gene in splenocyte colonies derived from the bone marrow of reconstituted
      mice and in cells of other hemopoietic and non-hemopoietic organs was studied
      during the life. It was shown that the lentivirus vector can persist for a long
      time and replicate in hemopoietic cells as an episome.

PMID- 12802426
TI  - Functional association of immediate early gene c-fos with nuclear matrix.
AB  - Accumulation of c-fos gene locus DNA in the nuclear matrix of hepatocyte nuclei
      was observed during induction of c-fos with cycloheximide. No enhanced
      association with the nuclear matrix was detected for inactive immunoglobulin gene
      locus. The use of endogenous DNAses allows isolation of nuclear matrix
      preparations enriched with transcribing chromatin.

PMID- 12802427
TI  - Partial elimination of lymphocytes in mice with Ehrlich carcinoma.
AB  - Elimination of about 30% lymphocyte population was observed in female Balb/c mice
      on day 11 after transplantation of Ehrlich carcinoma in comparison with animals
      without tumor. It was hypothesized that the eliminated population can block the
      tumor growth. Studies of the temporal and quantitative parameters of lymphocyte
      elimination with consideration for tumor size are considered to be perspective.
      The described model can be used for studies of immunodeficiency in animals with
      tumors.

PMID- 12802428
TI  - Local expression of cytokine genes in uterine adnexa and endometrium of women
      with pyoinflammatory adnexal diseases.
AB  - Changes in the local expression of IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL
      12, IL-15, IL-18, TNF-alpha, IFN-gamma- and TGF-beta(2) genes in the uterine
      adnexa and endometrium were studied in women with pyoinflammatory adnexal
      diseases. Examination of tissue specimens from the uterine adnexa involved in
      inflammation revealed a direct correlation in the levels of mRNA production
      between IL-6 and IL-10 (r=0.93, p<0.1), IL-6 and IL-4 (r=0.96, p<0.01), IL-10 and
      IL-4 (r=0.91, p<0.01), IL-12 and IFN-gamma (r=0.98, p<0.01). Expression of IL-4
      gene increased 5.1-fold (p=0.001), IL-6 2-fold (p=0.007), IL-8 90.2-fold
      (p=0.009), IL-10 2.9-fold (p=0.008), IL-12 2.3-fold (p=0.3), and TGF-beta(2) gene
      10.3-fold (p=0.1). In the endometrium of women with pyoinflammatory adnexal
      diseases only IL-10 gene expression increased (15.6-fold, p=0.007).

PMID- 12802429
TI  - Tissue hypoxia and intestinal dysbiosis in children with tuberculosis.
AB  - We studied the role of autochthonous microflora from body cavities in the
      development of tissue hypoxia and instability of cell membranes. In children with
      tuberculosis dysbiosis manifested in nonspecific quantitative changes in the
      intestinal microflora and the presence of coxsackievirus antigens in the urine.
      DNA-containing viruses with pronounced immunosuppressive activity (e.g.,
      herpesvirus, measles virus, and rubella virus) were found in most children.
      Microbiological and virological changes were accompanied by the appearance of
      laboratory signs for tissue hypoxia, which included inhibition of Krebs cycle
      dehydrogenases and alpha-glycerophosphate pathway in blood lymphocytes.
      Regression analysis revealed a relationship between the content of
      extraintestinal coxsackieviruses and inactivation of alpha-glycerophosphate
      dehydrogenase, succinate dehydrogenase and ratio of facultatively anaerobic
      bacteria in microbiocenosis, and expression of acid phosphatase and total
      population of malonate-positive enterobacteria, staphylococci, yeasts, and
      enterococci.

PMID- 12802430
TI  - Morphological and stereological characteristics of myocardial remodeling in aged
      spontaneously hypertensive SHR rats.
AB  - Myocardial remodeling in SHR rats with age-related hypertrophy was characterized
      by elimination of cardiomyocytes, their hypertrophy, and marked increase in the
      volume of the connective tissue. The count of cardiomyocytes with contracture
      injuries and subsegmental contractures increased, and pronounced perivascular and
      interstitial sclerosis developed in the hypertrophic myocardium of SHR rats.
      Damage to the microcirculatory bed manifested in degenerative changes and
      destruction of some endotheliocytes. Signs of atypical intracellular regeneration
      in myofibrils and impairment of their longitudinal orientation were revealed in
      cardiomyocytes in the late stage of compensatory hypertrophy.

PMID- 12802431
TI  - NO-ergic neurons of rat nucleus gracilis during acute pain.
AB  - Histochemical staining for NADPH diaphorase showed that the number of NO-ergic
      neurons in the nucleus gracilis of rat brain increased within the first few hours
      of pain stimulation. Initially, the changes were noted on the side of lesion, but
      then involve both halves of the nucleus. It was assumed that nucleus gracilis
      participates in processing of acute pain information.

PMID- 12802432
TI  - Structure and function of the thymus during adaptation of rats to
      hypergravitation.
AB  - Five-day exposure to hypergravitation (2g) induced structural and functional
      changes in the thymus: intensification of cell destruction and inhibition of
      mitotic activity of lymphocytes in all functional components of the organ. This
      leads to a significant (2-fold) decrease in thymus weight, area of the thymus
      cortex on histological section, blurring of the corticomedullary interface
      because of lymphocyte depletion of the cortical matter. The size and number of
      thymic bodies decrease 3.4 times compared to the control. This indicates that by
      day 5 of continuous hypergravitation (2g) exposure the lymphoid tissue does not
      completely adapt to hypergravitation.

PMID- 12802433
TI  - Structural and metabolic characteristics of liver acini in dogs with acute
      cholecystitis.
AB  - Structural and metabolic changes in liver tissue in dogs with acute cholecystitis
      were studied by histological, histoenzymatic, and biochemical methods. It was
      found that the development of destructive inflammatory processes in the
      gallbladder wall induces morphological damage to the liver tissue, which
      correlates with metabolic disorders in this organ and leads to liver dysfunction.

PMID- 12802434
TI  - Functional morphology of blind and other processes in the lymph capillary system.
AB  - "Blind" lymph capillaries of the diaphragmatic tendon center were studied in
      normal rabbits and after injections of India ink, yellow cadmium, chicken
      erythrocyte suspensions, and whole chicken blood into the abdominal cavity. Three
      groups of blind capillaries differing by morphological and functional signs were
      distinguished. Some blind capillaries can deposit foreign particles. The process
      of intracapillary endothelial growth is described.

PMID- 12802435
TI  - Pathohistological and ultrastructural study of systemic vasculopathy (Fabry
      disease).
AB  - Pathomorphological analysis of skin biopsy specimens from patients with Fabry
      disease showed edema and mucoid swelling of vascular walls in the skin,
      pronounced telangiectasias, endotheliocyte degeneration and death, compensatory
      proliferation of pericytes, and mast cell hyperplasia. Ultrastructural study
      revealed transformation of vascular cells (endotheliocytes and pericytes) into
      depocytes accumulating large specific polymorphic granules of varying electron
      density with fine regular striation, which is pathognomonic for Fabry disease.
      The complex of these structural changes is interpreted as manifestation of
      systemic vasculopathy.

PMID- 12802436
TI  - Morphology of the cerebellum in the progeny of female rats exposed to long-term
      emotional stress before pregnancy.
AB  - The structure of the cerebellum was studied in 40-day-old progeny of female rats
      exposed to 3-week emotional stress and mated with intact males after 10 days and
      in controls (progeny of intact females). The cerebellum in the experimental group
      was smaller, the nucleus and cytoplasm of Purkinje cells were smaller, the
      concentration of RNA in their cytoplasm and increased, the percentage of dark
      Purkinje cells increased, and the concentration of lipids in the molecular
      cortical layer and white matter decreased.

PMID- 12802437
TI  - The volume of diagnostic information and coefficient of examination completeness
      during pericardial inflammation.
AB  - The volume of diagnostic information during pericardial inflammation in small
      animals was calculated.

PMID- 12802438
TI  - Age-associated endocrine dysfunctions and approaches to their correction.
AB  - This review discusses age-specific functional changes in different components of
      the endocrine system (pituitary, epiphysis, adrenals, and gonads), their role in
      aging and age-specific diseases, and possible approaches to correction of
      endocrine disorders and prevention of accelerated aging.

PMID- 12802439
TI  - Acetylcholine and ATP hyperpolarize endothelium via activation of different types
      of Ca(2+)-activated K+ channels.
AB  - Experiments on rat thoracic aorta showed that ATP and acetylcholine hyperpolarize
      endothelial cell via selective activation of low (SK) and intermediate (IR)
      conductance Ca(2+)-activated K(+)channels, respectively. It was hypothesized that
      ATP- and acetylcholine-activated Ca(2+)-signals are spatially separated and
      generated in plasma membrane regions with predominant localization of SK- and IR
      channels, respectively.

PMID- 12802440
TI  - Changes in caval blood flow and right atrial pressure in response to
      catecholamines.
AB  - The type and magnitude of changes in blood flow in the anterior (cranial) and
      posterior (caudal) caval veins and shifts in the mean right atrial pressure
      induced by catecholamines (epinephrine and norepinephrine) were studied in acute
      experiments on cats. It was found that irrespective of right atrial pressure
      shifts, the increase in the blood flow in the anterior vena cava was more
      pronounced than in the posterior vena cava and was determined by blood
      redistribution due to more pronounced increase in vascular resistance in the
      abdominal aorta basin.

PMID- 12802441
TI  - Effect of ionic medium on carbacholine-induced membrane depolarization in
      lumbricus terrestris somatic muscle cells.
AB  - Carbacholine depolarizes Lumbricus terrestris myocyte membrane. Addition of
      verapamil, tetrodotoxin, removal of K(+), Cl(-), and Ca(2+), and replacement of
      Ca(2+)with Mn(2+)in the bathing solution did not prevent the carbacholine-induced
      decrease in resting potential, but in a sodium-free medium carbacholine was
      ineffective. It was hypothesized that depolarization of the sarcolemma resulting
      from activation of cholinomimetic-sensitive channel-receptor complex of the
      Lumbricus terrestris somatic muscle cells is primarily determined by sodium
      permeability of the membrane.

PMID- 12802442
TI  - Effect of thyrotropin-releasing hormone on the development of cardiac arrhythmias
      during stimulation of sensorimotor cortex in cats.
AB  - Preliminary intravenous injection of thyrotropin-releasing hormone in a dose of
      20  g/kg to cats with developing myocardial ischemia during stimulation of the
      cerebrocortical sensorimotor zone had a pronounced antiarrhythmic effect.

PMID- 12802443
TI  - Thermoregulatory reactions to cooling in rats with hereditary arterial
      hypertension.
AB  - Experiments on rats with hereditary stress-induced arterial hypertension showed
      that hypertension shortened the latency and increased the amplitude of
      constrictive reaction of skin blood vessels to rapid cooling characterized by
      more rapid and considerable increase in blood norepinephrine content compared to
      slow cooling. Decreased thermal threshold of metabolic reaction suggests that
      arterial hypertension is accompanied by changes in both the vascular walls and
      tissues involved in metabolic reaction to cooling.

PMID- 12802444
TI  - Role of leukotrienes in stress-induced damage to the heart.
AB  - Experiments on rabbits with epinephrine-induced damage to the heart showed that
      progression of necrotic degenerative processes in the myocardium is augmented by
      increased content of prostaglandin F(2alpha)and predominance of constrictive over
      vasodilatory effects in the E and F(2alpha)prostaglandin system. Twenty-four
      hours after injection of epinephrine we observed an increase in blood
      concentrations of myofibrillar fraction of creatine phosphokinase, serotonin and
      histamine, and the F(2alpha)/E prostaglandin ratio. The concentration of
      leukotriene B(4)increased during the urgent adaptation period, which correlated
      with a decrease in elastic properties of erythrocytes. In vitro passage of
      erythrocytes through a 2.5-micro capillary sieve sharply decreased, which played
      an important role in the progression of myocardial and cerebral hypoxia and
      ischemia. Myocardial necrosis and endothelial dysfunction developed 24 h later
      aggravate these pathological shifts.

PMID- 12802446
TI  - Effect of radiation on prothrombin interactions with cell membrane fragments.
AB  - Binding of (125)I-labeled prothrombin to normal and radiation-damaged (1 and 3.5
      Gy) fragments of cell membranes was studied. Irradiation significantly increased
      adsorption capacity of cell membranes for (125)I-prothrombin. It was concluded
      that phase rearrangement of phospholipids serves as the molecular basis for
      increased thrombogenicity of cell membranes.

PMID- 12802445
TI  - Effects of oxytocin and prostaglandin F(2alpha) (enzaprost) on platelet
      aggregation.
AB  - The effects of uterotonic agents (oxytocin and enzaprost) on platelet aggregation
      in pregnant and nonpregnant women were studied by low-angle light scattering. In
      nonpregnant women oxytocin produced different effects on ADP-induced platelet
      aggregation: potentiation at low (<200 nM) and inhibition at high (>400 nM) ADP
      concentrations. In pregnant women oxytocin did not modulate ADP-induced platelet
      aggregation or this effect was negligible. Enzaprost competitively inhibited ADP
      induced platelet aggregation in all examined women (inhibition constant 84.8+/
      25.7 nM).

PMID- 12802447
TI  - Relative binding activity of new antigestagens with progesterone receptors in
      human hyperplastic endometrium.
AB  - We determined the content and binding capacity of progesterone receptors in the
      endometrium of patients with adenomatous and fibroid polyps, adenocystic
      hyperplasia, and atypical hyperplasia before and after gestagen therapy.
      Hyperplasia of the endometrium was accompanied by changes in affinity of
      cytosolic progesterone receptors for antigestagens, which provides the
      possibility of individual correction of hormone therapy.

PMID- 12802448
TI  - Effect of nooglutil on benzodiazepine withdrawal syndrome and binding of 3H
      spiperone with D2 receptors in rat striatum.
AB  - A new nootropic preparation nooglutil (N-(5-oxynicotinoyl)-L-glutamic acid), a
      positive modulator of AMPA receptors for glutamate, administered
      intraperitoneally in a dose of 70 mg/kg reduced anxiety of rats in the Vogel
      conflict test after 24-h withdrawal from chronic diazepam treatment (4 mg/kg
      intraperitoneally for 45 days). Nooglutil (5 nM-750 microM) had no effect on in
      vitro binding of (3)H-spiperone in intact rats. Systemic administration of 50
      mg/kg nooglutil in vivo increased the dissociation constant and density of
      D(2)receptors. Increasing the dose to 100 mg/kg abolished this effect. Our
      findings suggest that nooglutil produces an indirect effect on the brain
      dopaminergic system under normal and pathological conditions and this effect is
      probably mediated via the glutamatergic system.

PMID- 12802449
TI  - Use of zafirlucast, cysteine-containing leukotriene antagonist, in epinephrine
      induced heart injury.
AB  - Combination of preventive and repeated (after 12 h) injections of zafirlucast in
      a daily dose of 40 mg/kg to animals with epinephrine-induced heart injury
      essentially decreased the content of leukotriene C(4), but did not prevent the
      increase of leukotriene B(4)content in the blood, though decreased its content in
      comparison with the level observed 24 h after epinephrine injection by 11%. Two
      injections of zafirlucast had a favorable impact on serotonin content in the
      myocardium (this parameter decreased by 19%), promoted a decrease in epinephrine
      content and normalization of the norepinephrine/epinephrine ratio, did not change
      prostaglandin content and ratio, and slightly decreased histamine content in the
      myocardium. The effect of zafirlucast can be explained by a decrease of oxidative
      stress. Zafirlucast decreased blood content of myofibrillar fraction of creatine
      phosphokinase (by 22%) and slightly improved elastic characteristics of
      erythrocytes. These results suggest that zafirlucast can be added to combined
      therapy of necrotic, stress-induced, hypoxic, and ischemic injuries of the
      myocardium.

PMID- 12802450
TI  - Effect of Erysod (erythrocyte superoxide dismutase) on blood concentration of
      reactive oxygen species in patients with severe burns and burn shock.
AB  - The dynamics of blood concentrations of reactive oxygen species and LPO products
      in patients with thermal injuries of different severity was studied. Monitoring
      of these parameters by chemiluminescent and spectrophotometric techniques helps
      to predict the course of burn shock and prevent complications. Erysod (0.004%
      solution, 33-66 microg/min, daily dose 24-32 mg) added to antishock infusion
      therapy during the early periods after injury suppressed generation of free
      radicals (by 20% after 15 min and by 30-40% after 24 h), promoted normalization
      of their contents, and reduced damage to visceral organs during acute period of
      thermal injury.

PMID- 12802451
TI  - Effect of natural biocorrector Namivit on free-radical processes in abdominal
      delivery.
AB  - Free-radical oxidation parameters were measured in the blood of women during
      preparation to cesarean section and postoperative period and in the umbilical
      blood and placenta. A course of biocorrector Namivit before the intervention
      prevented intensification of free-radical processes in the mother-placenta-fetus
      system.

PMID- 12802452
TI  - Detection of Chlamydophila pneumoniae in mouse respiratory ciliated epithelium
      using targeted sections of the lung tissue.
AB  - Chlamiophila pneumoniae were detected in targeted sections of mouse lung tissue
      by means of transmission electron microscopy and immunofluorescent staining.
      Incorporation of microorganisms into the axonemal matrix of cilia was observed 24
      h after infection. The ciliary axoneme was characterized by pronounced swelling.
      At the late stages Chlamiophila pneumoniae were present in cytoplasmic vacuoles.
      Structural abnormalities and dysfunction of mucociliary clearance followed by
      incorporation of Chlamiophila pneumoniae into the cytoplasm of epitheliocytes
      were revealed in the early stage of infection. The proposed method allows
      studying the very early events of Chlamiophila pneumoniae infection.

PMID- 12802453
TI  - Interferon system in women with genital papillomavirus infection receiving
      immunomodulatory therapy.
AB  - The interferon system was studied in women with genital papillomavirus infection.
      In most patients the interferon system was activated, while the ability of
      lymphocytes to respond to inductors decreased. Laserotherapy and immunomodulatory
      therapy with larifan, ridostin, and viferon for 1 month normalized blood
      interferon concentration (39.4% patients) and interferon-gamma production by
      lymphocytes in response to inductors (87.9% patients). After laser monotherapy
      these parameters returned to normal only in 13.2 and 7.6% patients, respectively.
      Correlation and regression analyses showed that changes in the interferon system
      were synchronized after immunomodulatory therapy. These data indicate that
      immunomodulatory therapy produces a complex effect on the interferon system.
      Measurements of blood interferon level can be used to predict the effect of
      further treatment with interferon-gamma inductors.

PMID- 12802454
TI  - Expression of cytokine genes in adhesions on uterine tubes.
AB  - We studied expression of genes of interleukins, interferon-gamma, tumor necrosis
      factor-alpha, and transforming growth factor-beta(2) in adhesions on uterine
      tubes. In tubal adhesions the intensity of production of mRNA for proinflammatory
      cytokines, antiinflammatory cytokine interleukin-10, and regulator of cell
      proliferation surpassed that in normal tissues by 2.5-7.4, 2.2, and 50.2 times,
      respectively. Correlations were found between production of mRNA for tumor
      necrosis factor-alpha and transforming growth factor-beta(2), interleukin-12, and
      interferon-gamma and interleukin-12 and transforming growth factor-beta(2). Our
      results suggest that expression of these genes during adhesion formation is
      regulated by the feedback mechanism.

PMID- 12802455
TI  - Structural and functional characteristics of lymphocytes in chronic carriers of
      tick-borne encephalitis virus.
AB  - Study of the surface phenotype, structure of plasma membrane, and activity of DNA
      repair system in peripheral blood lymphocytes from patients with different
      clinical forms of tick-borne encephalitis associated with long persistence of the
      virus revealed a pronounced imbalance between lymphocyte subpopulations,
      increased microviscosity of the plasma membrane lipid phase, and decreased
      activity of the DNA repair system in lymphocytes.

PMID- 12802456
TI  - Spontaneous death of bone marrow and peripheral blood cells during remission of
      acute lymphoblastic leukemia in children.
AB  - Programmed antileukemic chemotherapy is associated with prolonged cytotoxic
      effects on not only tumor cells, but on intact bone marrow and peripheral blood
      cells as well. The maximum spontaneous cell death is observed immediately after
      the end of therapy. It decreases with time after therapy, but does not reach the
      level observed in healthy subjects and does not depend on the type of therapy.
      The percentage of dead cells in peripheral blood directly correlates with the
      percentage of dead cells in the bone marrow. The processes of cell death in the
      peripheral blood and bone marrow are synchronous and parallel.

PMID- 12802457
TI  - Expression of cytokine genes in blood mononuclear cells in women with
      pyoinflammatory diseases of adnexa uteri.
AB  - Production of interleukin, interferon-gamma, and transforming growth beta(2)
      factor mRNA in peripheral blood mononuclear cells was studied in women with
      pyoinflammatory diseases of adnexa uteri. Predominant expression of Th1
      proinflammatory cytokine genes in patients was demonstrated. Production of
      interleukins 4 and 8 mRNA decreased 200- and 60-fold, respectively, in comparison
      with that in healthy women. One month and a half after extirpation of fallopian
      tubes the cytokine production in blood mononuclear cells shifted towards
      antiinflammatory cytokines, expression of interleukin-8 gene returned to normal,
      and expression of interleukin-4 gene increased.

PMID- 12802458
TI  - Inductive activity of retinal peptides.
AB  - We studied the effect of retinal polypeptide Retinalamin on multipotent
      ectodermal cells of the early gastrula of Xenopus laevis. Neuronal
      differentiation of the early gastrula ectoderm including the brain, retina, and
      pigment epithelium depended on Retinalamin concentration.

PMID- 12802459
TI  - Modification of the uterotropic effect produced by estrogens in aging rats.
AB  - We studied the influence of various methods for correction of age-related changes
      (administration of N-acetyl-L-cysteine, vitamins C and E, melatonin, and
      carnosine and swimming training) on the realization of estrogens effects in
      ovariectomized rats. The proliferation index in the endometrium decreased in 12
      14-month-old control animals. The weight of the uterus, percentage of "comets",
      and average length of their tail in estradiol-treated rats far surpassed the
      corresponding parameters in control animals. Administration of melatonin and N
      acetyl-L-cysteine and swimming training corrected these genotoxic abnormalities.
      Our results indicate that aging induces incomplete variant of the phenomenon for
      switching of estrogen's effects (increase in the severity of genotoxic damage
      without facilitation of the hormonal effect). These methods for correction of age
      related changes have not only common, but also distinguishing characteristics
      compared to correction of changed induced by drinking of ethanol in various
      concentrations, whole body gamma-irradiation, and exposure to tobacco smoke.

PMID- 12802460
TI  - Ultrastructural characteristics of cell populations in the gastric and duodenal
      mucosa during psoriasis.
AB  - In biopsy specimens of the gastric and duodenal mucosa from patients with
      psoriasis we revealed severe degenerative and dystrophic changes in cells of the
      surface and glandular epithelium with destruction of functionally important
      cytoplasmic organelles. The stroma of the gastric mucosa was characterized by
      hyperplasia of the lymphoid tissue, formation of numerous lymphoid follicles, and
      destruction of the endothelium in microvessels. These changes are interpreted as
      the syndrome of regenerative and plastic insufficiency.

PMID- 12802461
TI  - Allergic dermatoses associated with chronic opisthorchiasis during antihelminthic
      therapy.
AB  - We studied skin biopsy specimens from patients with allergic dermatoses
      associated with opisthorchiasis. Structural changes in the epidermis and derma
      were presented by degenerative and destructive changes in epitheliocytes with a
      pronounced membranolytic component, hemodynamic disturbances in the derma,
      disorganization of the connective tissue, and progressive fibrosis. Combination
      therapy including antihelmintic drug produced a positive effect, which was
      associated with induction of regenerative processes in basal epidermal cells,
      stabilization of the basal membrane, and normalization of the dermoepidermal
      junction. Our findings indicate that opisthorchiasis plays an important role in
      the pathogenesis of allergic dermatoses.

PMID- 12802462
TI  - Changes in myocardial metabolism and ultrastructure of myocardial microvessels
      during pharmacological and cold cardioplegia under hypothermic conditions without
      perfusion.
AB  - A combination of pharmacological and cold cardioplegia in with hypothermia
      without perfusion in open-heart surgery guarantee the reversible character of
      shifts in energy and free radical balance in the myocardium. However, this
      procedure can impair coronary micricirculation due to structural and functional
      changes in microvessel endothelium. Our results demonstrate that new
      cytoprotective approaches are extremely needed for cardiac protection during
      surgery.

PMID- 12802463
TI  - Morphological criteria for normalization of menstrual function in women with
      spontaneous abortion.
AB  - Normalization of the menstrual function in women with spontaneous abortion
      receiving sorbent and bioresonance (extremely high-frequency) therapy was
      evaluated by morphological criteria (correspondence of structural changes in the
      endometrium to the phase of the menstrual cycle). The absence of microvilli and
      cilia on the apical surface of surface and glandular epitheliocytes, presence of
      intranuclear tubules and giant mitochondria in the cytoplasm, and signs of
      apocrine secretion in epitheliocytes attested to the luteal phase of the cycle.

PMID- 12802464
TI  - Effect of injection of testosterone derivatives to pregnant rats on the brain of
      their one-day offspring.
AB  - Intramuscular injection of Sustanon-250, a drug with testosterone derivatives of
      various action rate and duration, to rats on day 19 of gestation affected brain
      development in their offspring. This effect manifested in greater brain weight
      and neocortex thickness, smaller density of neurons in the developing cortical
      layer V, and larger size of these neurons and their nuclei and cytoplasm in
      comparison with control neonatal rats. These data attest to accelerated cerebral
      development in the offspring of experimental rats in comparison offspring of
      control rats.

PMID- 12802465
TI  - Modeling of thermal skin injury for the development of local treatment drugs.
AB  - The paper describes simple and reliably reproducible methods of inducing
      superficial and deep skin burns (both infected and non-infected) in rats, which
      model IIIa and IIIb degree burns in humans. These methods reduce the costs and
      accelerate the development of local preparations.

PMID- 12802466
TI  - Extravasal occlusion of large vessels with titanic clips: efficiency,
      indications, and contraindications.
AB  - The mechanism of extravasal occlusion of blood vessels with titanic clips
      "Atrauclip" and "Ligaclip extra" was studied in order to reveal indications and
      contraindications to their use. Occlusion with the clips of both types was
      ineffective in vessels with a diameter of >7.0 mm. Arteritis or the presence of
      an intravascular occlusion facility in the vessel were also the contraindications
      for clip occlusion. In overcases the procedure of occlusion with titanic clips
      was efficient and atraumatic.

PMID- 12802467
TI  - [Congresses: virtual versus traditional].

PMID- 12802468
TI  - [Reimbursement of the PET in oncology in Europe: a questionnaire based survey].
AB  - AIM: The discussion in Germany about the reimbursement of the (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in oncology should make
      use of the experience from the other European countries. METHOD: A questionnaire
      was sent to 23 PET-institutions in Europe, outside from Germany, in January 2003.
      The questions were about the number of PET-institutions, the regulations for
      reimbursement, the accepted indications, the recognized types of PET-machines and
      the level of reimbursement. RESULTS: 16 PET-institutions from 10 different
      countries answered. The relation of PET-institutions to inhabitants ranged from
      1:500,000 (B) and 1:1,000,000 (D, A, CH) to approximately 1:4,000,000 (I, E, F,
      NL). In Belgium, the Netherlands, France, Great Britain, Italy, Finland,
      Switzerland, and Spain reimbursement was possible and a broad spectrum of
      indications was accepted, respectively. The reimbursement was not restricted to
      official indications. In Germany and Austria PET was not generally covered for
      the patients insured by the national health insurance. An annual sum of
      approximately 450,000 euro was granted to the recognized PET-institutions in
      Belgium and France. In Denmark the clinics and their PET-centres were owned by
      the government, PET was part of the clinical routine oncology. If PET was
      separately covered the average level of reimbursement for the whole-body PET
      using a full-ring detector was 1200 euro. The reimbursement of the coincidence
      gammacamera differed from the "dedicated" PET in most European countries.
      CONCLUSION: In Europe there is an increasing tendency to cover the well
      documented PET indications in oncology.

PMID- 12802469
TI  - Imaging small animals with positron emission tomography.
AB  - During the past few years many research centers have successfully applied their
      knowledge of positron emission tomography (PET) to construct PET scanners which
      are dedicated to image small animals such as rats and mice. Although there are
      many in-house built systems which are used in laboratory environments, only a few
      of them are commercially available at this time. This review will give an
      overview of dedicated animal PET systems with their technical description and
      main physical characteristics. Graphical analysis of spatial resolution against
      absolute sensitivity allows a comparison of the most important characteristics of
      each camera. The quadHIDAC, a PET scanner recently installed at the Department of
      Nuclear Medicine, University Hospital Munster, acquires images with sub
      millimeter spatial resolution. A (18)F-FDG whole body image of a mouse with small
      structures like the left ventricle of the heart clearly visualized, demonstrates
      its excellent spatial resolution.

PMID- 12802470
TI  - [18F-Deoxyglucose PET for the staging of oesophageal cancer: influence of
      histopathological subtype and tumour grading].
AB  - AIM: Evaluation of the influence of histopathologic sub-types and grading of
      primaries of oesophageal cancer, relative to their size and location, on the
      uptake of (18)F-deoxyglucose (FDG) as measured by positron emission tomography
      (PET). METHODS: 50 consecutive patients were evaluated. There were four drop-outs
      due to previous surgical and/or chemotherapeutical treatments and thus in 46
      patients (28 squamous cell carcinomas and 18 adenocarcinomas) a pretherapeutic
      PET evaluation of the primary including a standard uptake value (SUV) was
      obtained. In 42 cases data on tumour grading were available also. RESULTS:
      Squamous cell carcinomas (SCC) were in 7/13/8 cases located in the proximal,
      medial and distal part of the oesophagus, respectively the grading was Gx in 3, G
      2 in 12, G2-3 in 7, and G3 in 6 cases. The SUV(max) showed a mean of 6.5+/-2.8
      (range 1.7-13.5). Adenocarcinomas (ACA) were located in the medial oesophagus in
      two cases and otherwise in its distal parts. Grading was Gx in one, G2 in 4, G2-3
      in 3, G3 in 3, G3-4 in 3, and G4 in one case. The mean SUV(max) was 5.2+/-3.2
      (range 1-13.6) and this was not significantly different from the SCC. Concerning
      the tumour grading there was a slight, statistically not relevant trend towards
      higher SUV(max) in more dedifferentiated cancer. DISCUSSION: SCC and ACA of the
      oesophagus show no relevant differences in the FDG-uptake. While there was a
      significant variability of tumour uptake in the overall study group, a
      correlation of SUV and tumour grading was not found.

PMID- 12802471
TI  - [Bone scintigraphy and clinical outcome in rheumatoid gonarthritis].
AB  - AIM: For evaluation of the effect of radiosynoviorthesis (RSO) on the early and
      delayed uptake of (99m)Tc-biphosphonates and its relation to clinical outcome we
      studied these variables before and after radiosynoviorthesis performed on 41
      knees affected by rheumatoid arthritis. METHOD: Thirty-seven patients with
      rheumatoid gonarthritis were treated by intraarticular injection with 185 MBq
      yttrium-90 citrate. In four of them both knees were treated so that 41 therapies
      were evaluated. On the average 35 days before and 120 days after
      radiosynoviorthesis, the early and delayed uptake of (99m)Tc-diphosphonate (DPD)
      was measured with a planar gamma camera. Early and late DPD uptake was quantified
      as a ratio between count values derived from rectangular ROIs placed on the knee
      treated and on the ipsilateral thigh. The severity of clinical symptoms was
      assessed on two 3-point rating scales averaged. RESULTS: 30 of the 41 cases
      favorably responded to radiosynoviorthesis. There was a significant correlation
      between clinical outcome and pretherapeutic early DPD uptake (EDU) (p<0.05), but
      not between outcome and pretherapeutic late DPD uptake (DDU). In the whole group,
      EDU decreased in approximately 76% of cases after therapy (p<0.05), DDU in 54%
      (p>0.05). In 25 of the 30 responders EDU decreased; EDU increased or remained
      constant in five of the eleven non-responders. The correlation between outcome
      and the difference in EDU was significant (r = 0.344; p<0.05). There was no such
      significant relationship between the difference between pre- and posttherapeutic
      DDU and clinical course. CONCLUSION: Three-phase bone scintigraphy may contribute
      to predict and assess the success of radiosynovior-thesis in rheumatoid arthritis
      of the knee joint.

PMID- 12802472
TI  - Myocardial indium-111-antimyosin uptake in essential hypertension.
AB  - AIM: Evaluation of myocardial uptake of (111)In-anti-myosin antibodies in
      patients with essential hypertension for the verification of our hypothesis that
      it may increase in stage 1 in the left ventricle as a result of myocardial
      damage. PATIENTS, METHODS: Twelve men (mean age: 59+/-2.4 years) suffering from
      angina like symptoms and essential hypertension in clinical stage 1 according to
      the JNC-VI criteria were included into the study. These patients showed normal
      perfusion as revealed by thallium-201 myocardial study and coronary angiography.
      Left ventricular mass index was determined in echocardiography. Planar antimyosin
      images were obtained 48 h after the intravenous injection of the tracer. Heart to
      lung ratios were calculated as a parameter of myocardial tracer uptake using
      appropriate region of interests; values>1.52 were considered as abnormal.
      RESULTS: We observed increased anti-myosin uptake (mean: 1.71+/-0.12) consistent
      with myocardial damage in 11 of 12 patients. Nine of 12 patients had a left
      ventricular hypertrophy with left ventricular mass index values (mean: 131
      g/m(2)+/-9.48) above 115 g/m(2). Heart to lung ratio was correlated significantly
      to left ventricular mass index (r = 0.902, p<0.001) and duration of hypertension
      (r = 0.948, p<0.001). CONCLUSION: Our results suggest that (111)In-antimyosin
      imaging may indicate myocyte damage in early phases of hypertensive heart
      disease.

PMID- 12802473
TI  - [Beta-radiation exposure at the finger tips during the radionuclide synovectomy].
AB  - AIM: The radiation synovectomy is a widespread therapeutic option in rheumatoid
      arthritis. However, data for the beta-radiation exposure are rare. The aim of
      this study was to determine the personal dose equivalent H(P) (0.07) of the skin
      of the hands. METHODS: Thermo-luminescence detectors (TLDs) were attached at all
      fingertips of the therapist, the radiochemist and the nurse. In summary, the
      measurement of beta-exposure occurred in 155 joints at 6 days with different
      radio-nuclides ((169)Er, (186)Re, (90)Y). RESULTS: The greatest beta exposure
      were show at the forefinger (L-Ff) and thumb (L-Th) of the left hand, with which
      the therapist (right hander) fixed the injection needle. In 52 treated finger
      joints (1204 MBq (169)Er), 29 treated large joints (2405 MBq (186)Re) and 15
      treated knees (3100 MBq (90)Y) we found a cumulative beta exposure over all
      radionuclides of 190 mSv at L-Ff and 48 mSv at L-Th. The specific beta exposure
      for the individual radio-nuclides showed beta exposures of 0.56 mu Sv/MBq for
      (169)Er and 1.52 mu Sv/MBq for (186)Re-186 at the L-Ff. With using a manipulator
      the beta-exposure ((90)Y) could reduced from 22,09 to 0.42 mu Sv/MBq at the L-Ff.
      The greatest beta exposures for the radiochemist was 119 mSv at the L-Ff for all
      radionuclides. CONCLUSION: In usual techniques of radiation synovectomy the (90)Y
      produced the greatest part of radiation exposure. Especially at the L-Ff it might
      exceed the German limit for the official dosimetry service at the skin ( section
      sign 55 Strl-SchV). Using a holding forceps we can keep the legal rules and can
      reduce considerably the beta exposure.

PMID- 12802474
TI  - [Guideline for in vivo- and in vitro procedures for thyroid diseases (version
      2)].
AB  - The version 2 of the guideline for diagnostic standards of thyroid disorders is
      an update of the guideline published in 1999 and describes standards of in vitro
      and in vivo procedures. The following statements are modified: In vitro
      procedures: When measurement of the TSH-receptor antibodies is indicated, the
      guideline recommends the use of a second generation assay (recombinant human TSH
      receptor as antigen). The functional assay sensitivity for the measurement of
      thyroglobulin should reach a value < or =1 ng/ml. Molecular genetic tests (RET
      proto-oncogene) are indicated in patients with a newly diagnosed medullary
      thyroid cancer and in the relatives of patients with hereditary medullary thyroid
      cancer. In vivo procedures: The sonographic examination should use a probe with a
      frequency of at least 7.5 MHz. Indications for the thyroid scintigraphy: nodule
      size > or =1 cm in diameter, autonomous goitre/nodule with clinical or
      subclinical hyperthyroidism, necessity of a differentiation between Graves'
      disease and chronic lymphocytic thyroiditis, therapy control after a definitive
      treatment and - in individual cases - the follow-up of untreated autonomous
      nodules.

PMID- 12802475
TI  - [Procedure guideline for radioiodine test (version 2)].
AB  - The version 2 of the procedure guideline for radioiodine test is an update of the
      guideline published in 1999. The following statements were added or modified: The
      procedure guideline discusses the pros and cons of a single measurement or of
      repeated measurements of the iodine-131 uptake and their optimal timing.
      Different formulas are described when one, two or three values of the radioiodine
      kinetic are available. The probe with a sodium iodide crystal, alternative or
      additionally the gamma-camera using the ROI-technique are instrumentations for
      the measurement of iodine-131 uptake. A possible source of error is an
      inappropriate measurement (sonography) of the target volume. The patients'
      preparation includes the withdrawal of antithyroid drugs 2-3 days before
      radioiodine administration. The patient has to avoid iodine-containing medication
      and the possibility of additives of iodide in vitamin- or electrolyte
      supplementation has to be considered.

PMID- 12802476
TI  - [Procedure guideline for thyroid scintigraphy (version 2)].
AB  - The version 2 of the procedure guideline for thyroid scintigraphy is an update of
      the procedure guideline published in 1999. The procedure guideline considers the
      current amendment of legislative rules (Richtlinie Strahlenschutz in der Medizin
      2002). Indication and use of radiopharmaceuticals have to be confirmed by the
      specialist in nuclear medicine. Activities of 75 MBq technetium-99m, respectively
      of 10 MBq iodine-123 should not be exceeded without an individual justification.
      The interpretation of the scintigraphy requires the knowledge of the patients'
      history, the palpation of the neck, the laboratory parameters, and of the
      sonography. The interpretation of the technetium-99m uptake requires the
      knowledge of TSH concentration.

PMID- 12802477
TI  - [Procedure guideline for iodine-131 whole-body scintigraphy for differentiated
      thyroid cancer (version 2)].
AB  - The version 2 of the procedure guideline for iodine-131 whole-body scintigraphy
      for differentiated thyroid cancer is an update of the procedure guideline
      published in 1999. The following statements are added or modified: The two
      alternatives of an endogenous TSH-stimulation by the withdrawal of the thyroidal
      hormone medication and of an exogenous TSH-stimulation by the injection of the
      recombinant human TSH (rhTSH) have an equal sensitivity for the diagnostic use of
      radioiodine and for the measurement of thyroglobulin. Image acquisition under
      rhTSH is obtained approximately 48 h after the radioiodine administration, while
      an interval of about 72 h is preferred under endogenous TSH-stimulation. If
      iodine-negative metastases are expected, the feasibility of scintigraphy using
      (99m)Tc sestamibi or preferably positron emission tomography using (18)F
      fluorodeoxyglucose should be considered. The sensitivity of FDG-PET is increased
      by TSH-stimulation. Before planning the iodine-131 scintigraphy the patient has
      to avoid iodine-containing medication and the possibility of additives of iodine
      in vitamin- and electrolyte-supplementation has to be considered.

PMID- 12802478
TI  - Distribution of antigenic oligomannosyl side chains in the cell wall mannans of
      several strains of Candida tropicalis.
AB  - In order to clarify the distribution of antigenic oligomannosyl side chains in
      the cell wall mannans of the pathogenic yeast Candida tropicalis, the chemical
      structure of mannans isolated from four C. tropicalis strains was investigated
      using nuclear magnetic resonance, two-dimensional homonuclear Hartmann-Hahn (2D
      HOHAHA) spectroscopy. Two-dimensional maps of the 2D-HOHAHA clearly showed the
      distribution of oligomannosyl side chains in the mannans. The linear side chain
      Manalpha1-3Manalpha1-(2Manalpha1-)(n)2Man [n> or =2] is present in the mannans
      from C. tropicalis IFO 0589 and IFO 1400, but not in the mannans from IFO 0199
      and IFO 1647. The mannan of IFO 0589 is the only mannan with the branched side
      chains, Manalpha1-3[Manalpha1-6]Manalpha1-(2Manalpha1-)(n)2Man and Manalpha1
      2Manalpha1-3[Manalpha1-6]Manalpha1-(2Manalpha1-)(n)2Man [n> or =2]. However, this
      mannan lacked the phosphate group and the beta-1,2-linked oligomannosyl side
      chain which are features of this group. The mannans of the C. tropicalis strains
      IFO 0589 and IFO 1400 possessed the side chains containing an alpha-1,3-linked
      mannose residue previously observed in Candida albicans.

PMID- 12802479
TI  - Improved vectors for transcriptional/translational signal screening in
      corynebacteria using the melC operon from Streptomyces glaucescens as reporter.
AB  - The tyrosinase operon ( melC) from Streptomyces glaucescens was cloned and
      functionally expressed in Brevibacterium lactofermentum and Corynebacterium
      glutamicum under the control of the promoter of the kan gene from Tn 5.
      Recombinant corynebacterial cells containing the tyrosinase operon produced
      melanin on agar plates and in liquid culture when supplemented with copper and
      tyrosine. A conjugative bifunctional replacement vector for
      transcriptional/translational signal screening (pEMel-1) was constructed using
      expression of the melC operon from S. glaucescens, which can be used for cloning
      promoter sequences as EcoRI- NdeI fragments. When the DNA fragments with promoter
      activity such as cspBp or trpp were inserted into pEMel-1, B. lactofermentum
      harboring the chimeric plasmids produced melanin at different stages of growth,
      allowing temporal detection of promoter activity. The vector was also used to
      detect the activity of a Streptomyces promoter ( xysAp), which was inactive in B.
      lactofermentum, after PCR mutagenesis. The melC operon can be used for the
      visual, inexpensive (compared to the high price of starch azure for amylase
      detection), and non-selective (in contrast to the kan or cat genes) screening of
      several thousand clones at high colony density without killing of the
      transformants due to the presence of iodine (as in the case of amylase assay).

PMID- 12802480
TI  - Genetic diversity of fast-growing rhizobia that nodulate soybean ( Glycine max L.
      Merr).
AB  - The fast-growing Rhizobium sp. strain NGR234, isolated from Papua New Guinea, and
      13 strains of Sinorhizobium fredii, isolated from China and Vietnam, were
      fingerprinted by means of RAPD, REP, ERIC and ARDRA. ERIC, REP and RAPD markers
      revealed a considerable genetic diversity among fast-growing rhizobia. Chinese
      isolates showed higher levels of diversity than those strains isolated from
      Vietnam. ARDRA analysis revealed three different genotypes among fast-growing
      rhizobia that nodulate soybean, even though all belonged to a subcluster that
      included Sinorhizobium saheli and Sinorhizobium meliloti. Among S. fredii
      rhizobia, two strains, SMH13 and HH303, might be representatives of other species
      of nitrogen-fixing organisms. Although restriction analysis of the nifD- nifK
      intergenic DNA fragment confirmed the unique nature of Rhizobium sp. strain
      NGR234, several similarities between Rhizobium sp. strain NGR234 and S. fredii
      USDA257, the ARDRA analysis and the full sequence of the 16S rDNA confirmed that
      NGR234 is a S. fredii strain. In addition, ARDRA analysis and the full sequence
      of the 16S rDNA suggested that two strains of rhizobia might be representatives
      of other species of rhizobia.

PMID- 12802481
TI  - Novel thermo-acidophilic bacteria isolated from geothermal sites in Yellowstone
      National Park: physiological and phylogenetic characteristics.
AB  - Moderately thermophilic acidophilic bacteria were isolated from geothermal (30-83
      degrees C) acidic (pH 2.7-3.7) sites in Yellowstone National Park. The
      temperature maxima and pH minima of the isolates ranged from 50 to 65 degrees C,
      and pH 1.0-1.9. Eight of the bacteria were able to catalyze the dissimilatory
      oxidation of ferrous iron, and eleven could reduce ferric iron to ferrous iron in
      anaerobic cultures. Several of the isolates could also oxidize tetrathionate. Six
      of the iron-oxidizing isolates, and one obligate heterotroph, were low G+C gram
      positive bacteria ( Firmicutes). The former included three Sulfobacillus-like
      isolates (two closely related to a previously isolated Yellowstone strain, and
      the third to a mesophilic bacterium isolated from Montserrat), while the other
      three appeared to belong to a different genus. The other two iron-oxidizers were
      an Actinobacterium (related to Acidimicrobium ferrooxidans) and a
      Methylobacterium-like isolate (a genus within the alpha -Proteobacteria that has
      not previously been found to contain either iron-oxidizers or acidophiles). The
      other three (heterotrophic) isolates were also alpha-Proteobacteria and appeared
      be a novel thermophilic Acidisphaera sp. An ARDREA protocol was developed to
      discriminate between the iron-oxidizing isolates. Digestion of amplified rRNA
      genes with two restriction enzymes ( SnaBI and BsaAI) separated these bacteria
      into five distinct groups; this result was confirmed by analysis of sequenced
      rRNA genes.

PMID- 12802482
TI  - ADP-dependent glucokinase from the hyperthermophilic sulfate-reducing archaeon
      Archaeoglobus fulgidus strain 7324.
AB  - The hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus strain
      7324 has been shown to degrade starch via glucose using a modified Embden
      Meyerhof pathway. The first enzyme of this pathway, ADP-dependent glucokinase,
      was purified 600-fold to homogeneity. The enzyme is a monomeric protein with an
      apparent molecular mass of 50 kDa. It had a temperature optimum at 83 degrees C
      and showed a significant thermostability up to 100 degrees C. The enzyme was
      highly specific for ADP and glucose as substrates; it did not use ATP, CDP, UDP,
      or GDP as phosphoryl donors, or mannose, fructose and fructose 6-phosphate as
      phosphoryl acceptors (at 80 degrees C). Only glucosamine was phosphorylated at
      significant rates. The apparent K(m) values for ADP and glucose (at 50 degrees C)
      were 0.07 mM and 0.78 mM, respectively; the apparent V(max) value was about 50
      U/mg at 50 degrees C and 350 U/mg at 80 degrees C. Divalent cations were required
      for maximal activity; Mn(2+), Mg(2+ )and Ca(2+), which were most effective, could
      be replaced partially by Cu(2+), Ni(2+), Co(2+) and Zn(2+). The N-terminal amino
      acid sequence (42 amino acids) of ADP-dependent glucokinase was almost identical
      to that of ADP-dependent glucokinase from Thermococcus litoralis. In the genome
      of the closely related Archaeoglobus fulgidus strain VC16 a homologous gene for
      ADP-dependent glucokinase could not be identified.

PMID- 12802483
TI  - Liver transplantation for metastatic colon adenocarcinoma: report of a case with
      10 years of follow-up without recurrence.
AB  - Because of dismal mid-term and long-term results, secondary liver cancer is
      considered an absolute contra-indication to cadaveric liver transplantation, with
      the relative exception of metastases of symptomatic neuro-endocrine cancers. The
      authors present in this report the case of a patient who has been enjoying 10
      years of cancer-free survival after liver transplantation as rescue therapy for
      acute liver failure after liver resection for isolated hepatic metastasis of
      colon adenocarcinoma. This case shows that in some highly selected cases, liver
      transplantation may be curative in patients with liver metastases of colon
      carcinoma.

PMID- 12802484
TI  - Cefazolin does not accelerate gastric emptying in the critically ill.
AB  - OBJECTIVE: To evaluate the effect of intravenous cefazolin on gastric emptying
      measured by the C-13 octanoic acid breath test. DESIGN: Prospective, double
      blind, cross-over, randomised, placebo-controlled trial. SETTING: Mixed
      multidisciplinary intensive care unit in a university hospital. PATIENTS:
      Fourteen critically ill, mechanically ventilated patients. INTERVENTIONS: After a
      4-h fast patients received either 50 mg cefazolin or 20 ml saline over 20 min
      immediately prior to measurement of gastric emptying. The next day the study was
      repeated with the alternative therapy. MEASUREMENTS AND RESULTS: Breath samples
      were analysed for the concentration of (13)CO2 by mass spectrometer, and the
      gastric emptying coefficient (GEC) and half-emptying time (t(50)) were
      calculated. Results are mean (standard deviation). Data were analysed with the
      paired t-test (saline vs cefazolin). Two patients were excluded for technical
      problems. Twelve patients remained (six male/six female), aged 57 (+/-16) years,
      with an APACHE II score of 20 (+/-8). Both GEC and t(50) were unchanged after
      administration of cefazolin compared with placebo (t(50) cefazolin, 138 (+/-54)
      vs saline 122 (+/-46) min, P=0.32; GEC cefazolin 3.27 (+/-0.83) vs saline 3.55
      (+/-0.6), P=0.24). Two patients had abnormal t(50) after saline and five after
      cefazolin. There was no order effect of the study day. CONCLUSION: In
      mechanically ventilated patients, cefazolin had no effect on gastric emptying.
      These data do not support the use of low-dose cefazolin as a pro-kinetic agent in
      critically ill patients.

PMID- 12802485
TI  - Prediction of prolonged ventilatory support in blunt thoracic trauma patients.
AB  - OBJECTIVE: To identify predictors of prolonged (>7 days) mechanical ventilation
      (MV) in patients with blunt thoracic trauma. DESIGN: Prospective analysis of
      consecutive patients. SETTING: Adult intensive care unit (ICU) in a teaching,
      tertiary-care hospital. PATIENTS AND PARTICIPANTS: Sixty-nine patients (53 men,
      16 women) with thoracic trauma having a median age of 35 (range 17-85) years and
      a median injury severity score (ISS) of 29 (range 14-41) were enrolled in the
      present study. Associated injuries included head-neck (77%), extremities (72%),
      external (67%), abdomen-pelvis (67%), and face (55%). INTERVENTIONS: Patient
      surveillance and data collection. MEASUREMENTS AND RESULTS: Thirty-three (48%) of
      the 69 patients required prolonged ventilatory support, ranging in duration from
      8 to 38 (median 18) days. Logistic regression analysis revealed that advancing
      age (odds ratio=1.04, p=0.04), severity of head injury (odds ratio=1.92,
      p=0.008), and bilateral thoracic injuries (odds ratio=12.80, p<0.0001) were
      significant and independent predictors of long-lasting MV. In contrast, gender,
      injuries affecting the other body regions (face, abdomen-pelvis, extremities, and
      external), laparotomy in patients with abdominal injury, or PaO(2)/FIO(2) on
      admission in the ICU, were unrelated to prolonged MV. CONCLUSIONS: In thoracic
      trauma patients admitted in the ICU, prolonged mechanical ventilation was
      primarily determined by presence of bilateral chest injuries, age, and degree of
      neurotrauma. This information may help in planning the long-term care of such
      patients.

PMID- 12802486
TI  - Effect of propofol on adhesion of activated platelets to leukocytes in human
      whole blood.
AB  - OBJECTIVE: To investigate the effect of propofol and its solvent Intralipid on
      the adhesion of activated platelets to leukocytes in vitro. DESIGN AND SETTING:
      Prospective study in an experimental laboratory. PARTICIPANTS: Sixteen healthy
      volunteers. INTERVENTIONS: Whole blood was incubated for 60 min with propofol (4,
      40 micro g/ml), an equal volume of Intralipid 10% or phosphate-buffered saline
      (PBS). After stimulation with adenosine-5-diphosphate (ADP) platelet-leukocyte
      adhesion and platelet surface expression of P-selectin, GPIb and fibrinogen
      binding to platelets were evaluated by flow cytometry. MEASUREMENTS AND RESULTS:
      The 4 micro g/ml concentration of propofol did not alter binding of platelets to
      leukocytes, expression of P-selectin, GPIb and fibrinogen binding to platelets.
      The 40 micro g/ml concentration of propofol reduced spontaneous and ADP-induced
      formation of platelet-neutrophil conjugates compared with PBS and the equal
      volume of Intralipid. In addition, binding of ADP-activated platelets to
      monocytes were also inhibited by 40 micro g/ml propofol. Following incubation
      with propofol, platelets showed reduced binding of fibrinogen in the unstimulated
      and ADP-stimulated blood samples as well as a lower percentage of platelets with
      bound fibrinogen. Effects dependent on the solvent Intralipid were enhanced
      adhesion of platelets to monocytes in comparison with propofol (40 micro g/ml)
      and PBS. CONCLUSION: In clinically used concentrations, propofol does not alter
      the adhesion of platelets to leukocytes in vitro. At ten-fold anesthetic
      concentration propofol reduced the formation of platelet-neutrophil and platelet
      monocyte conjugates. We suggest that this effect is due to an inhibition of
      fibrinogen-binding to platelets by propofol. These effects were all independent
      of the propofol carrier Intralipid.

PMID- 12802487
TI  - Noninvasive pressure support versus proportional assist ventilation in acute
      respiratory failure.
AB  - BACKGROUND: Although conventional pressure ventilation (PSV) decreases the rate
      of intubation in acute respiratory failure, patient-ventilator dyssynchrony is a
      frequent cause of failure. In proportional assist ventilation (PAV), pressure is
      applied by the ventilator in proportion to the patient-generated volume and flow;
      therefore, there is automatic synchrony between the patient's effort and the
      ventilatory cycle. OBJECTIVE: The aim of this study was to compare the effects of
      PSV and PAV during noninvasive ventilation in the treatment of acute respiratory
      failure. DESIGN: Prospective randomised study. SETTING: A multidisciplinary 24
      bed intensive care unit of an acute-care teaching hospital in Alicante, Spain.
      PATIENTS. This study included 117 consecutive adult patients with acute
      respiratory failure randomised to noninvasive ventilation delivered by PSV ( n =
      59) or PAV ( n = 58). MEASUREMENTS AND RESULTS: There were no statistically
      significant differences between patients assigned to each mode of ventilation
      with regard to baseline parameters and aetiological diagnoses of acute
      respiratory failure. With regard to outcome data, no significant differences were
      observed between PSV and PAV in the frequency of intubation (37% vs 34%),
      mortality rate (29% vs 28%), and mean length of stay. Subjective comfort (0-10
      visual analogue scale) was rated higher and intolerance occurred less frequently
      (3.4% vs 15%, P = 0.03) in the PAV than in the PSV mode. CONCLUSIONS: Although
      PAV seems more comfortable and intolerance occurred less frequently, no major
      differences exist in terms of physiological improvement or in terms of outcomes
      when comparing PSV and PAV.

PMID- 12802489
TI  - Unexpected left main stem bronchus cardiac output measurement.

PMID- 12802488
TI  - Red blood cell rheology in sepsis.
AB  - Changes in red blood cell (RBC) function can contribute to alterations in
      microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and
      neutrophil deformability impair the passage of these cells through the
      microcirculation. While the role of leukocytes has been the focus of many studies
      in sepsis, the role of erythrocyte rheological alterations in this syndrome has
      only recently been investigated. RBC rheology can be influenced by many factors,
      including alterations in intracellular calcium and adenosine triphosphate (ATP)
      concentrations, the effects of nitric oxide, a decrease in some RBC membrane
      components such as sialic acid, and an increase in others such as 2,3
      diphosphoglycerate. Other factors include interactions with white blood cells and
      their products (reactive oxygen species), or the effects of temperature
      variations. Understanding the mechanisms of altered RBC rheology in sepsis, and
      the effects on blood flow and oxygen transport, may lead to improved patient
      management and reductions in morbidity and mortality.

PMID- 12802490
TI  - Case report medication error: oral antibiotics and simethicone accidentally
      injected intravenously.

PMID- 12802491
TI  - Noninvasive positive pressure ventilation delivered by helmet vs. standard face
      mask.
AB  - OBJECTIVE: This bench and human study compared large and small helmets with face
      mask (FM) for delivery of noninvasive positive pressure ventilation. DESIGN: A
      lung simulator was employed, and the human study involved six healthy subjects.
      We evaluated a continuous high-flow (CPAPHF), low flow (CPAPLF), ventilator
      (CPAPVENT) CPAP, and pressure support ventilation (PSV 10 and 20 cmH2O). In the
      human study we used CPAPHF, CPAPVENT, and PSV 5 cmH2O. PEEP was 5 cmH2O.
      MEASUREMENTS: In the bench study during CPAP we measured the negative airway
      pressure time product (areaCPAP), i.e., the area of airway pressure (Paw) under
      PEEP and during PSV the pressure airway time product (areaPSV), i.e., the area of
      Paw from onset to end of inspiratory flow. In the human study we measured the
      breathing pattern and work of breathing (WOB). RESULTS: In the bench study during
      CPAPLF the helmets had a lower areaCPAP than the FM, while during CPAPHF the
      three interfaces had similar areaCPAP. Using CPAPVENT and PSV the FM reduced
      areaCPAP and increased areaPSV compared to helmets. At 20 cmH2O of PSV using
      helmets areaPSV was similar to that obtained at 10 cmH2O of PSV using the FM. In
      human study using CPAPHF and CPAPVENT the tree interfaces had similar effects on
      breathing pattern and WOB, while using PSV the FM reduced WOB more than helmets.
      CONCLUSIONS: During CPAPLF helmets were more efficient than FM, while during
      CPAPHF the three interfaces were comparable. Using CPAPVENT and PSV, FM was more
      efficient than helmets

PMID- 12802492
TI  - HLA-DR as a marker for increased risk for systemic inflammation and septic
      complications after cardiac surgery.
AB  - OBJECTIVE: This study investigated the predictive value of a decrease in monocyte
      HLA-DR expression as an early marker for postoperative SIRS and septic
      complications. We hypothesized that decreased HLA-DR levels in the first 24 h
      after cardiac surgery is not related to postoperative SIRS/sepsis. We also
      compared HLA-DR levels of patients with postoperative complications to those with
      an uncomplicated course. DESIGN AND SETTING: Prospective observational study in a
      tertiary care postoperative intensive care unit. PATIENTS: Eighty five
      consecutive patients undergoing cardiac surgery. MEASUREMENTS AND RESULTS:
      Expression of HLA-DR on monocytes was analyzed by flow cytometry using a new
      quantitative and well standardized technique. Arterial blood samples were
      collected before induction of anesthesia, immediately after admission to the ICU,
      and on the first postoperative day. Postoperative HLA-DR expression was
      significantly decreased in all patients. There were no significant differences in
      HLA-DR expression during the first 24 h after surgery in patients with
      uncomplicated course and those developing SIRS or septic complications.
      CONCLUSIONS: In patients undergoing cardiac surgery the monitoring of pre- and
      immediate postoperative HLA-DR levels during the first 24 h does not help to
      predict increased risk for postoperative SIRS/sepsis or infectious complications.

PMID- 12802494
TI  - Atopic eczema in early childhood could be protective against Type 1 diabetes.
AB  - AIMS/HYPOTHESIS: According to the Th1/Th2 paradigm Type 1 diabetes and atopic
      diseases are assumed to be mutually exclusive on the individual level. We
      analysed the association between Type 1 diabetes and atopic diseases in a case
      control design in order to test the hypothesis that atopic diseases in early
      childhood could protect against Type 1 diabetes. METHODS: We carried out a
      nationwide population-based case-control study enrolling 760 cases newly
      diagnosed with Type 1 diabetes under five years of age between July 1992 and
      December 1995 and 1871 controls randomly selected from the general population and
      individually matched on sex, age and place of residence. Information on atopic
      diseases was obtained by a mailed parent-administered questionnaire. Data were
      analysed by multivariate logistic regression adjusting for potential confounders
      (family history of diabetes, social status, duration of overall breast feeding,
      number of children in family, maternal age at delivery). RESULTS: Atopic eczema
      was less frequent in diabetic (13.3%) than in non-diabetic children (18.0%) and
      was significantly associated with a reduced risk of Type 1 diabetes. The adjusted
      odds ratio was 0.71 (95% CI 0.53-0.96). Hay fever and asthma were not
      significantly associated with diabetes risk (OR 0.98 (95% CI 0.47-2.01) and 1.46
      (95% CI 0.70-3.06), respectively). CONCLUSION/INTERPRETATION: In this large
      population-based case-control study in pre-school children an inverse association
      was observed between atopic eczema and Type 1 diabetes. Thus, in accordance with
      the Th1/Th2 paradigm development of atopic eczema in early childhood could be
      protective against childhood Type 1 diabetes.

PMID- 12802493
TI  - ACE-inhibitors but not endothelin receptor blockers prevent podocyte loss in
      early diabetic nephropathy.
AB  - AIMS/HYPOTHESIS: It was the aim of our study to investigate the influence of a
      selective ET-A receptor antagonist LU 135252 alone and in combination with the
      ACE-inhibitor, trandolapril on podocyte number and morphology in streptozotocin
      diabetic rats. METHODS: Male Sprague-Dawley rats were injected with 65 mg
      streptozotocin i.v. and subsequently developed diabetes. Animals were left
      untreated or received daily either trandolapril (0.3 mg/kg body weight), LU
      135252 (50 mg/kg body weight) or a combination of both. After 6 months the
      experiment was terminated. Glomerular geometry and cellularity were assessed by
      stereological techniques. Protein expression of TGF-beta, ET-1, PDGF-AB,
      fibronectin, desmin and alpha-smooth muscle cell actin was investigated by
      immunohistochemistry. RESULTS: The mean number of podocytes per glomerulus was
      lower (86+/-17 vs. 138+/-25; p<0.05) and mean podocyte volume was higher in
      untreated diabetic animals than in non-diabetic controls. Only ACE-i alone and in
      combination, but not ET(A)-RB alone prevented loss of podocytes and podocyte
      hypertrophy. In diabetic rats, increased numbers of PCNA positive and p27(kip1)
      positive cells (mainly podocytes) were reduced by all treatments, but only ACE-i
      decreased numbers of desmin positive podocytes and tubulointerstitial expression
      of TGF-beta. Albuminuria was increased in untreated diabetes and was prevented
      only by ACE-i and combination treatment. CONCLUSION/INTERPRETATION: Podocyte
      hypertrophy and degeneration is an early event in diabetic nephropathy leading to
      a loss of podocytes. Treatment with an ACE-i, but not with an ET(A)-RB, prevented
      the development of albuminuria as well as damage and loss of podocytes. The well
      known anti-proteinuric effect of ACE-i is presumably due at least in part to
      conservation of podocyte structure. Increased plasma endothelin-1 (ET-1)
      concentrations and urine excretion of ET-1 have been documented in patients with
      diabetes and proteinuria [1]. It has been shown that experimental diabetes
      mellitus increases renal ET-1 gene transcription [2]. To assess the relevance of
      the ET-system in the pathogenesis of renal structural changes in the model of the
      STZ-induced diabetic rat we compared the effect of an ET(A)-receptor specific
      antagonist with the well known beneficial effect of an ACE-i, especially on
      podocyte cell number and morphology.

PMID- 12802496
TI  - Keratinocyte growth factor and beta-cell differentiation in human fetal
      pancreatic endocrine precursor cells.
AB  - AIMS AND HYPOTHESIS: Keratinocyte growth factor (KGF) is a member of the heparin
      binding fibroblast growth factor family with a high degree of specificity for
      epithelial cells in vitro and in vivo. Our aim was to study the effect of KGF on
      beta-cell growth and differentiation on islet-like cell clusters derived from
      human fetal pancreas. METHODS: We investigated the effects of KGF, in vitro, on
      beta-cell differentiation from undifferentiated pancreatic precursor cells and in
      vivo after transplantating human fetal pancreatic cells into athymic rats treated
      with KGF. RESULTS: Treatment of islet-like cell clusters with KGF in vitro did
      not change the number of insulin producing cells, as measured by the measurement
      of insulin content or DNA. The in vivo treatment of recipient rats with KGF
      increased the number of beta cells within the grafts 8 weeks after
      transplantation. At this time, glucose-stimulated insulin secretion was evaluated
      by glucose stimulation tests in rats bearing the transplants. Measurements of
      human C-peptide concentrations after glucose challenge showed that the newly
      differentiated beta cells in the KGF-treated group were functionally competent as
      opposed to the control group, where the graft failed to release insulin
      appropriately. CONCLUSION/INTERPRETATION: These findings suggest that in vivo,
      KGF is capable of inducing human fetal beta-cell expansion. The growth promoting
      effect of KGF on beta cells occurred mainly through the activation of ductal cell
      proliferation and their subsequent differentiation into beta cells.

PMID- 12802495
TI  - Evidence for an important role of perilipin in the regulation of human adipocyte
      lipolysis.
AB  - AIMS/HYPOTHESIS: We investigated the role of the adipocyte-specific protein
      perilipin for lipolysis in humans. METHODS: Perilipin protein content and
      lipolysis rates were measured in human subcutaneous fat cells of non-obese (n=10)
      and obese (n=117) women. Single nucleotide polymorphisms in the perilipin gene
      were examined in obese subjects. RESULTS: Basal and noradrenaline-induced rates
      of lipolysis were two to fourfold increased (p<0.01) and perilipin protein
      content decreased 50% (p=0.005) in adipocytes of the obese women. In subjects
      matched for body mass index and fat-cell volume, a high rate of lipolysis was
      associated with a low adipocyte content of perilipin (p=0.01). Adipocyte content
      of perilipin was inversely correlated with the circulating concentrations of
      glycerol (r=0.62) and non-esterified fatty acids (n=0.49). A gene polymorphism
      (rs891460 A/G) in intron 6 was common. In AA subjects basal and noradrenaline
      induced lipolysis were 50 to 100% times more rapid (p</=0.01) and the adipocyte
      perilipin content was about 80% reduced (p=0.005) as compared to GG carriers.
      Intermediate values were found in AG carriers. CONCLUSIONS/INTERPRETATION:
      Perilipin seems important for the regulation of lipolysis in human fat cells.
      Obesity and a polymorphism in the perilipin gene associate with decreased protein
      content of perilipin and increased basal (unstrained) and noradrenaline-induced
      lipolysis. Low perilipin content also associate with high in vivo lipolytic
      activity. Perilipin could be a factor behind impaired lipolysis in insulin
      resistant conditions.

PMID- 12802497
TI  - Compensatory hypochloraemic alkalosis in diabetic ketoacidosis.

PMID- 12802498
TI  - Glutamine:fructose-6-phosphate aminotransferase enzyme activity is necessary for
      the induction of TGF-beta1 and fibronectin expression in mesangial cells.
AB  - AIMS/HYPOTHESIS: Increased flux through the hexosamine biosynthetic pathway with
      glutamine:fructose-6-phosphate aminotransferase (GFAT) as a rate-limiting enzyme
      has been linked to the enhanced bioactivity of the prosclerotic cytokine TGF
      beta1, a key mediator in the development of diabetic nephropathy and possibly
      other diabetic angiopathies. In this study we investigated the effect of enhanced
      expression of wild-type GFAT and two enzymatically inactive GFAT mutants on TGF
      beta1 synthesis in mesangial cells. METHODS: Mutated human GFAT expression
      vectors were prepared by PCR-site directed mutagenesis. Wild-type and mutated
      vectors were transfected into human embryonic kidney 293 cells and mesangial
      cells and GFAT enzyme activity was assessed by formation of glucosamine-6
      phosphate. Production of TGF-beta1 and fibronectin protein was examined by ELISA.
      RESULTS: Mutation of histidine 577 or lysine 676 to alanine led to a complete
      loss of GFAT enzyme activity. An increased concentration of wild-type GFAT in
      mesangial cells enhanced both TGF-beta1 and fibronectin production 1.5-fold,
      while mesangial cells transfected with the mutated GFAT constructs showed no
      effect. CONCLUSION/INTERPRETATION: The data indicate that the hexosamine pathway
      mediated induction of TGF-beta1 synthesis in mesangial cells is dependent on GFAT
      enzyme activity. Our results add to previous observations showing that the
      hexosamine pathway could increase the transcriptional activity of nuclear
      proteins leading to enhanced cytokine synthesis.

PMID- 12802499
TI  - Distribution of HERV-LTR elements in HLA-DQB1 alleles: comments on the article by
      Bieda et al.

PMID- 12802500
TI  - Multiple autoantibodies as predictors of Type 1 diabetes in a general population.

PMID- 12802501
TI  - Downregulation of carnitine acyltransferases and organic cation transporter OCTN2
      in mononuclear cells in healthy elderly and patients with myelodysplastic
      syndromes.
AB  - Changes in key enzymes of oxidative metabolism at the mitochondrial level are
      known to be associated with the aging process, apoptosis, and many diseases.
      Considering the risk of acquiring a myelodysplastic syndrome (MDS) with age, the
      aim of this study was to quantify mRNA synthesis of the carnitine
      palmitoyltransferases (CPT1 and CPT2), carnitine acetyltransferase (CRAT), human
      specific microsomal CPT, and OCTN2 (organic cation transporter) in mononuclear
      cells of healthy humans of different age groups and MDS patients. Using
      quantitative reverse transcriptase real-time PCR we compared mRNA synthesis of
      the above mentioned enzymes in mononuclear cells from peripheral blood of 23
      healthy persons (mean age 45 years), 9 blood and 22 bone marrow samples of 31 MDS
      patients with varying proportions of apoptotic cells (mean age 78 years), and
      blood samples of 30 age-matched controls. In addition, plasma carnitine levels
      were determined. Compared to younger adults, there was a 50% downregulation of
      CPT1 in elderly persons and in MDS patients. Reduction in CRAT, CPT 2, and OCTN2
      was more than 85%. Reduction in microsomal CPT was more pronounced in MDS
      patients than in age-matched controls (96% vs. 43%). In MDS bone marrow cells
      there was a negative correlation of CPT1 and CRAT with the relative proportion of
      apoptotic cells. Plasma carnitine values were similar in all groups. The
      described reduction in transcription of different genes in blood cells which is
      well known in different tissues may reflect a systemic signaling process,
      associated with aging, apoptosis, and MDS.

PMID- 12802502
TI  - Androgen receptor independent cardiovascular action of the antiandrogen
      flutamide.
AB  - We have previously shown that flutamide (specific antagonist of the androgen
      receptor) has antihypertensive effects. In the present study we examined the
      mechanisms of flutamide action in the vasculature. The vascular effects of
      flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats
      and from rats or mice lacking a functional androgen receptor ( tfm, testicular
      feminization mutation). The effect of flutamide on coronary flow was tested in
      isolated hearts. In addition, male hypertensive rats with tfm mutation were
      treated with flutamide, and blood pressure was monitored. Flutamide induced a
      relaxation of rat aortae from all the strains used (maximum relaxation at 10
      microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary
      flow. The aortic relaxation to flutamide was abolished by endothelium removal, or
      by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but
      not by calmodulin inhibition. Flutamide treatment attenuated the development of
      hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide
      produces direct vasodilation by inducing release of NO from the endothelium and
      causes subsequent activation of soluble guanylyl cyclase in an active androgen
      receptor independent manner. This response may contribute to the observed
      antihypertensive actions of flutamide.

PMID- 12802503
TI  - Evaluation of Aspergillus niger as host for virus-like particle production, using
      the hepatitis B surface antigen as a model.
AB  - The filamentous fungus Aspergillus niger was transformed with the hepatitis B
      virus S gene encoding the major viral envelope protein under control of the
      constitutive A. nidulans glyceraldehyde-3-phosphate dehydrogenase ( gpdA)
      promoter. Approximately seven copies of the expression cassette were integrated
      on the genome, resulting in high-level transcription of the S gene. Production of
      the 24-kDa S protein and a 48-kDa S protein dimer in the membrane-associated
      protein fraction of the recombinant A. niger strain was shown through Western
      analysis. Electron microscopy of partially purified recombinant S protein
      revealed the formation of spherical pseudoviral particles with a diameter of 22
      nm. The production level of hepatitis B pseudoviral particles was estimated to be
      0.4 mg/l culture, which compares favourably with the reported levels initially
      obtained in yeast, indicating the potential of the Aspergillus expression system
      as an alternative, cost-effective vaccine production system.

PMID- 12802504
TI  - Differential regulation of genes encoding manganese peroxidase (MnP) in the
      basidiomycete Ceriporiopsis subvermispora.
AB  - We previously identified and characterized three mnp genes coding for manganese
      peroxidase (MnP) in the white rot fungus Ceriporiopsis subvermispora. In this
      work, we assessed transcript levels of mnp genes in liquid cultures of this
      fungus grown under various conditions. In the absence of Mn(2+), mnp1 and mnp2
      mRNA were detected by Northern hybridization, irrespective of the lack of
      extracellular MnP activity. Addition of Mn(2+) to the cultures led to a marked
      increase in both transcripts, the highest titers being observed at 10 micro M
      Mn(2+). mnp1 mRNA was not detected at Mn(2+ )concentrations above 80 micro M,
      whereas mnp2 mRNA was still observed at 320 micro M Mn(2+). Differential
      regulation of these genes was confirmed by the addition of Cu(2+), Zn(2+), Ag(+)
      and Cd(2+). These metal ions dramatically elevated both transcripts and also
      allowed the detection of the mnp3 transcript. In most cases, the increase in mRNA
      levels was partially abolished by the simultaneous presence of Mn(2+), although
      the latter was strictly required to detect extracellular MnP activity. However,
      the lignin-related compound syringic acid specifically increased the mnp1
      transcript, although only in the absence of Mn(2+). These results indicate that
      there is no clear correlation between mnp mRNA levels and MnP activity. In
      addition, they strongly suggest that Mn(2+) plays a post-transcriptional role
      which is essential for the presence of active MnP in the extracellular fluid.

PMID- 12802505
TI  - Malo-ethanolic fermentation in Saccharomyces and Schizosaccharomyces.
AB  - Yeast species are divided into the K(+) or K(-) groups, based on their ability or
      inability to metabolise tricarboxylic acid (TCA) cycle intermediates as sole
      carbon or energy source. The K(-) group of yeasts includes strains of
      Saccharomyces, Schizosaccharomyces pombe and Zygosaccharomyces bailii, which is
      capable of utilising TCA cycle intermediates only in the presence of glucose or
      other assimilable carbon sources. Although grouped together, these yeasts have
      significant differences in their abilities to degrade malic acid. Typically,
      strains of Saccharomyces are regarded as inefficient metabolisers of
      extracellular malic acid, whereas strains of Sch. pombe and Z. bailii can
      effectively degrade high concentrations of malic acid. The ability of a yeast
      strain to degrade extracellular malic acid is dependent on both the efficient
      transport of the dicarboxylic acid and the efficacy of the intracellular malic
      enzyme. The malic enzyme converts malic acid into pyruvic acid, which is further
      metabolised to ethanol and carbon dioxide under fermentative conditions via the
      so-called malo-ethanolic (ME) pathway. This review focuses on the enzymes
      involved in the ME pathway in Sch. pombe and Saccharomyces species, with specific
      emphasis on the malate transporter and the intracellular malic enzyme.

PMID- 12802506
TI  - Unpaired genes do not silence their paired neighbors.
AB  - During meiotic chromosome pairing, a loop of unpaired DNA induces the silencing
      of all paired and unpaired homologous DNA via meiotic silencing, an RNA-mediated
      post-transcriptional gene-silencing mechanism. To test the effect of unpaired DNA
      on adjacent genes, we constructed strains containing the DNA of a transformation
      marker integrated immediately downstream of the Ascospore maturation-1 ( Asm-1)
      gene and tested whether this unpaired DNA silences asm-1(+). We conclude that
      unpaired downstream DNA has no effect on Asm-1 expression during meiosis or
      ascospore development, which suggests that the silencing signal produced by
      unpaired DNA does not propagate onto adjacent paired regions.

PMID- 12802507
TI  - Expression of the cercosporin toxin resistance gene ( CRG1) as a dicistronic mRNA
      in the filamentous fungus Cercospora nicotianae.
AB  - The CRG1 gene in Cercospora nicotianae encodes a transcription factor and is
      required for cercosporin toxin resistance and production. Cloning and sequencing
      of the downstream region of the CRG1 gene led to the discovery of an adjacent
      gene ( PUT1) encoding a putative uracil transporter. Expression of CRG1 and PUT1
      as assessed by Northern analysis indicated that, in addition to the expected
      monocistronic mRNAs (2.6 kb and 2.0 kb, respectively), a common 4.5-kb mRNA could
      be identified, using either a CRG1 or a PUT1 gene probe. The 2.6-kb transcript
      identified only by the CRG1 probe was expressed constitutively, whereas the 2.0
      kb transcript identified only by the PUT1 probe was differentially expressed in
      various media. Four cDNA clones containing CRG1, PUT1, and the CRG1- PUT1
      intergenic region were identified as part of the products from the 4.5-kb
      transcript. Both the 4.5-kb and 2.6-kb transcripts were not detectable in three
      crg1-disrupted mutants, using the CRG1 probe. The 2.0-kb transcript, but not the
      4.5-kb one was detected using the PUT1 probe in the three crg1-disrupted mutants.
      Taken together, we conclude that the 4.5-kb transcript is a dicistronic mRNA of
      both CRG1 and PUT1 in the fungus C. nicotianae. This is the first example of a
      dicistronic mRNA identified in filamentous fungi.

PMID- 12802508
TI  - Intravesical administration of doxorubicin to swine bladder using magnetically
      targeted carriers.
AB  - PURPOSE: The feasibility of using magnetic targeted carriers (MTC) to deliver
      doxorubicin intravesically was studied in normal swine bladder. MTCs are
      microparticles consisting of metallic iron and activated carbon. Doxorubicin is
      adsorbed to the activated carbon component of the MTCs (MTC-DOX) while the iron
      component provides magnetic susceptibility. This technology is designed for site
      specific delivery of a drug to a tumor in the presence of an externally applied
      magnetic field in order to achieve prolonged release of high localized drug
      concentrations by retention of MTCs in the region of interest. An intravesical
      route of administration was evaluated as intravesical chemotherapy is used in the
      treatment of bladder cancer. METHODS: The urethras of six swine were catheterized
      and Foley catheters were placed in their bladders. The effects of doses ranging
      from 10 to 80 mg doxorubicin adsorbed onto 300 to 800 mg MTCs were studied. A 30
      min period of magnetic targeting immediately followed dosing, in which an
      external magnet was placed on the skin surface over a predetermined site on the
      bladder. The subsequent retention and distribution of test material was evaluated
      by measurement of doxorubicin levels in plasma and histopathological examination
      of the bladder following treatment. Blood samples were taken prior to treatment
      and at 15 and 30 min after infusion for measurement of doxorubicin. The bladder
      was drained and rinsed thoroughly following the procedure. RESULTS: Plasma
      doxorubicin concentrations were less than the assay limit of detection (10 ng/ml)
      during the 30 min following dosing. MTCs were found within the bladder walls,
      predominantly at the targeted site where they were present at greater depths
      within the layers of the epithelium. The study results show that MTC-DOX can be
      targeted and retained within specific locations in the bladder using magnetic
      targeting. CONCLUSIONS: MTC delivery may allow greater exposure and specific
      deposition of drug at a defined site over intravesical administration of
      doxorubicin alone. The feasibility of this novel method of drug delivery was
      demonstrated and the results support further study for its potential use in
      treating bladder cancer.

PMID- 12802509
TI  - What is the arcuate eminence?
AB  - A study was made of 100 homogeneous CT scans of the petrous part of the temporal
      bone to determine whether or not the arcuate eminence (AE) is a good landmark for
      the superior semicircular canal (SSCC) in the suprapetrous approach to the
      internal acoustic meatus which is used in the extirpation of acoustic neuromas.
      Direct measurements were made on consecutive coronal sections, 1 mm thick. The AE
      was absent from the petrous surface in 15% of cases. It corresponded to the
      relief of the SSCC in 37% of cases; laterally, however, it was separated from the
      petrous cortex by bone whose thickness varied from 0.5 to 5 mm. Finally, in 48%
      of cases, the AE was not a good landmark for the canal although nonetheless it
      participated in the development of this bulge in 46% of cases, always lying
      towards the medial border of the pneumatized eminence. In addition, study of the
      coronal sections with MRI allowed us to confirm that the AE does not routinely
      correspond to the imprint of a temporal sulcus. The AE, whose presence on the
      petrous surface is due to the combined effects of the SSCC, the air cells of the
      petrous part of the temporal bone and the temporal sulci, is only a good guide to
      the SSCC in 37% of cases and should not be considered as a reliable surgical
      landmark.

PMID- 12802510
TI  - Anatomic feasibility of creating an inferior epigastric arterio-venous fistula to
      develop the internal thoracic artery with a view to coronary grafting.
AB  - Arterio-venous fistulae increase the diameter of their feeding artery. It may be
      advantageous to increase the diameter of the internal thoracic artery before its
      use for coronary grafting. A fistula applied directly to the internal thoracic
      artery may compromise its subsequent use as a coronary graft and is technically
      difficult and invasive. However, in view of the continuity between the internal
      thoracic artery and the inferior epigastric artery, it is possible to achieve the
      same effect by constructing a fistula on the latter. The purpose of this work was
      to determine, in a cadaveric study, the feasibility of carrying out an arterio
      venous fistula on the inferior epigastric artery so as to increase the caliber of
      the internal thoracic artery before coronary grafting. A morphologic study of the
      inferior epigastric artery and its vein and their relations as well as the
      feasibility of such a fistula was carried out on 10 cadavers. The epigastric
      artery measured 12.35+/-1.2 cm in length. Its diameter decreased from its origin
      towards it termination from 3.16+/-0.26 cm to 1.76+/-0.18 cm. There was a
      constant connection between the inferior and superior epigastric arteries. This
      connection was single in 30% of cases, double in 50% and through an anastomotic
      plexus of more than two vessels in 20%. The mean number of anastomotic
      connections was 1.8. The epigastric vein was constant with a diameter of 0.75+/
      0.06 mm at its origin and only sufficiently large to carry out a fistula at its
      termination (2.6+/-0.9 mm). In conclusion, this study indicates that it should be
      relatively simple to create a fistula between the inferior epigastric artery and
      either the inferior epigastric vein or the external iliac vein.

PMID- 12802511
TI  - Vascular anatomy for right colon lymphadenectomy.
AB  - Since the superior mesenteric artery (SMA) mostly originates on the left side of
      the superior mesenteric vein (SMV), the ileocolic artery (ICA) and the right
      colic artery (RCA) cross the SMV. Understanding the three-dimensional relation of
      these vessels is important for dissecting these arteries to their origin. Hence,
      we conducted a study of the vascular anatomy of the right colon in 27 cadavers.
      The RCA was separate from the SMA in eight cases (30%). The RCA passed the SMV
      either anteriorly (5 cases, 63%) or posteriorly (3 cases, 38%). In seven (88%) of
      these eight cases, the ICA was posterior to the SMV. The ICA was identified in
      all 27 cases, and passed the SMV anteriorly in nine cases (33%) and posteriorly
      in 18 cases (67%). Thus, the ICA and the RCA may pass on either side of the SMV.
      The surgeon must dissect the arteries with the SMV, being aware of both
      possibilities.

PMID- 12802512
TI  - Anatomical basis for the interposition of a gastric pouch between the ileum and
      the anus after total proctocolectomy.
AB  - After a total proctocolectomy, ileoanal continuity is achieved by an ileal pouch
      anal anastomosis. This anastomosis is not possible when the ileum cannot reach
      the anus. To avoid definitive ileostomy in this circumstance, we devised a
      gastric pouch, taken from the left half of the vertical portion of the stomach,
      vascularized by the right gastroepiploic pedicle, then interposed it between the
      ileum and the anus. The aim of this anatomical study on seven cadavers was to
      estimate the capacity of this gastric pouch to reach the anus. The distance
      between the caudal edge of the pubic symphysis and the apex of the pouch was
      measured. It is accepted that an ileal pouch always reaches the anus without
      tension if it comes down 6 cm below the caudal edge of the pubic symphysis. The
      apex of the gastric pouch reached a mean of 13.3 cm (range 10-18 cm) below the
      caudal edge of the pubic symphysis. This technique was then performed on four
      patients. The apex of the gastric pouch reached a mean of 12.5 cm (range 10-14
      cm) below the caudal edge of the pubic symphysis and always reached the anus.
      These findings emphasize that a gastric pouch interposed between the ileum and
      the anus after a total proctocolectomy has an excellent capacity to reach the
      anus without tension.

PMID- 12802513
TI  - Discomallear and malleomandibular ligaments: anatomical study and clinical
      applications.
AB  - Phylogenesis, ontogenesis and anatomy show the existence of two discomallear and
      malleomandibular ligaments, arising from the first branchial arch and uniting the
      middle ear with the temporomandibular joint and to the mandible. The intra
      articular discomallear ligament is the involuted tendon of the lateral pterygoid
      muscle on the primitive quadrato-articular joint. The malleomandibular ligament
      is the fibrous remnant of Meckel's cartilage. In the physiology of the
      temporomandibular joint, the discomallear ligament alone limits the anterior
      movement of the disc. Its stretching accompanies disco-condylar disunity,
      hyperlaxity and temporomandibular dislocation. The malleomandibular ligament,
      wrongly limited to its sphenomandibular part in classic anatomy, has no
      physiological role. However, it can be responsible for the dislocation of the ear
      ossicle chain after disarticulation or temporomandibular trauma. These two
      ligaments do not play any role in otological manifestations in dysfunction of the
      manducatory apparatus.

PMID- 12802514
TI  - Stabilized subcutaneous transposition of the ulnar nerve.
AB  - We treated 50 patients (average age 47.9 years) with a stabilized subcutaneous
      transposition of the ulnar nerve. The average follow-up period was 42.4 months.
      The indication was cubital tunnel syndrome in 19 patients and injuries around the
      elbow in 31 patients. Postoperatively, satisfactory results were obtained in all
      the patients, and there was no complication or aggravation of the preoperative
      symptoms. None of the patients experienced slipping back of the nerve to the
      cubital tunnel. In the 31 patients with injuries around the elbow, there was only
      one patient with transient aggravation of parasthaesiae in the ulnar nerve
      region. Stabilized subcutaneous transposition is a simple and less invasive
      procedure that can facilitate decompression and prevent slipping back of the
      nerve. This procedure also can be applied to patients with injuries around the
      elbow that require ulnar nerve transfer.

PMID- 12802516
TI  - Subtrochanteric metastatic lesions treated with the long gamma nail.
AB  - From 1996 to 2002, 39 consecutive intramedullary reconstructions (three
      bilateral) in 36 patients were performed in a group of subtrochanteric femoral
      metastatic bone disease using the long gamma nail (LGN). Reconstruction was
      performed prophylactically in 28 femurs and, for actual fractures in 11. All
      patients achieved good functional results with pain relief and improved mobility.
      No major intraoperative complication or long-term mechanical failures were
      observed. Minor technical, medical and implant related complications were seen in
      14 patients. The LGN is a valuable intramedullary reconstruction device with good
      functional outcome for the treatment of subtrochanteric femoral metastatic bone
      disease.

PMID- 12802517
TI  - Operative treatment of chronic Achilles tendinopathy.
AB  - Seventy-six patients with Achilles tendinopathies (n=86) operated between 1980
      and 1995 were retrospectively evaluated at an average follow-up of 13 (5-21)
      years. Total or gross partial ruptures were excluded. Patients' average age at
      surgery was 38 (18-58) years. The majority of patients were active in competitive
      or recreational sports. Tendinopathies were classified in peritendinitis,
      tendinosis, insertional tendinopathies, and mixed forms. The surgical technique
      depended entirely on the pathology encountered. For 32 cases of peritendinitis,
      results were excellent in 26, good in four, and poor in two. For eight cases of
      tendinosis, results were excellent in four and good in four. For 34 cases of
      insertional tendinopathy, results were excellent in 22, good in four, fair in
      four, and poor in four. For 12 cases of mixed tendinopathies, results were
      excellent in ten and good in two. Forty-nine patients (52 cases) were able to
      return to sport at the desired level.

PMID- 12802518
TI  - The effects of alphaGalCer-induced TCRValpha24 Vbeta11(+) natural killer T cells
      on NK cell cytotoxicity in umbilical cord blood.
AB  - PURPOSE: The first objective of this study was to investigate in vitro effects of
      alpha-galactosylceramide (alphaGalCer) on the proliferation of umbilical cord
      blood (UCB) natural killer T (NKT) cells and enhancement of their cytotoxicity.
      The second one is to examine whether purified NKT cells could affect the
      cytotoxicity of UCB-NK cells either in the presence or absence of dendritic cells
      (DCs). METHODS: Mononuclear cells (MNCs) from UCB were cultured for 2 weeks in
      the presence of IL-2 (100 U/ml), with or without alphaGalCer. The effect of
      neutralizing monoclonal antibodies (MoAb) against TCRValpha24 and CD1d was also
      examined. TCRValpha24 Vbeta11 double positive NKT cells were purified by FACS
      sorter and then cocultured with syngeneic isolated UCB(-)CD56(+)NK cells in
      either the presence or absence of DCs. The cytotoxicity against various malignant
      cell targets and cytokine production was determined. RESULTS: The addition of
      alphaGalCer induced human NKT cells to proliferate in UCB-MNCs to a greater
      extent than in adult PB-MNCs. However, it suppressed the cytotoxic activity
      against malignant cell targets. Anti-TCRValpha24 and CD1d MoAb recovered the
      cytotoxicity by inhibiting the proliferation of UCB-NKT cells. NKT cells
      cocultured with auto-DCs significantly increased NK cell cytotoxicity against
      K562, and Raji cells and produced IFN-gamma at much higher levels than UCB-NKT
      cells alone. CONCLUSION: In UCB samples, alphaGalCer-pulsed DCs and NKT cells
      acted together to enhance NK cytotoxicity in vitro.

PMID- 12802519
TI  - Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with
      adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM
      stage and clinical outcome.
AB  - INTRODUCTION: Recent studies have indicated that the cytokines produced by CD4(+)
      T helper type 1 (T(h)1) and type 2 (T(h)2) cells are critically important in
      antitumour immunity and perhaps clinical outcome. From this perspective, we
      investigated the immunocompetence of patients with previously untreated cancer of
      the oesophagus or oesophagogastric junction (OGJ) in relation to stage of disease
      and postoperative survival. METHODS: Blood samples were taken prior to surgery
      from 32 patients with adenocarcinoma of the oesophagus or OGJ. Ten healthy
      volunteers served as normal controls. T-cell and monocyte subpopulations were
      determined using flow cytometry. Monocyte as well as T(h)1- and T(h)2-lymphocyte
      cytokine levels were assessed in stimulated whole blood cultures. RESULTS:
      Absolute T-cell and monocyte (subset) counts as well as monocyte cytokine levels
      were similar among patients and controls. Production of T(h)1-type cytokines was
      higher in patients than in controls (IFN-gamma, p=0.01; IL-2, p=0.05), whereas
      T(h)2-type cytokine levels were comparable (IL-4, p=0.5; IL-13, p=0.3). T-cell
      CD4(+)/CD8(+) ratios decreased as pTNM stage worsened (stage I/II vs stage
      III/IV, p=0.009). Of all measured immunological parameters, only IL-2 production
      significantly affected both overall survival ( p=0.015) and disease-free survival
      ( p=0.0062). High IL-2 levels corresponded with a favourable prognosis.
      CONCLUSIONS: Patients awaiting surgery for adenocarcinoma of the oesophagus or
      oesophagogastric junction demonstrated a shift in the T(h)1/T(h)2 balance-in
      favour of T(h)1-compared with healthy volunteers. The ability of T cells to
      produce IL-2 was related to survival indicating a crucial role of T(h)1-type
      cells in antitumour immunosurveillance.

PMID- 12802520
TI  - Malignant fatty tumors: classification, clinical course, imaging appearance and
      treatment.
AB  - Liposarcoma is a relatively common soft tissue malignancy with a wide spectrum of
      clinical presentations and imaging appearances. Several subtypes are described,
      ranging from lesions nearly entirely composed of mature adipose tissue, to tumors
      with very sparse adipose elements. The imaging appearance of these fatty masses
      is frequently sufficiently characteristic to allow a specific diagnosis, while in
      other cases, although a specific diagnosis is not achievable, a meaningful
      limited differential diagnosis can be established. The purpose of this paper is
      to review the spectrum of malignant fatty tumors, highlighting the current
      classification system, clinical presentation and behavior, treatment and spectrum
      of imaging appearances. The imaging review will emphasize CT scanning and MR
      imaging, and will stress differentiating radiologic features.

PMID- 12802521
TI  - Fibroid in the buttock: an unexpected diagnosis.
AB  - Uterine leiomyomas (fibroids) are very common lesions with well-described imaging
      features. We present an unusual case of a fibroid which presented in the buttock
      with atypical clinical and imaging features in a woman who had had a previous
      hysterectomy. Despite extensive imaging and biopsies, the diagnosis was not
      suspected until pathological evaluation of the resected mass. The differential
      diagnosis for such a lesion, and the imaging and pathological features of
      fibroids, including atypical and parasitic leiomyomas, are discussed.

PMID- 12802522
TI  - Alagille syndrome: case report with bilateral radio-ulnar synostosis and a
      literature review.
AB  - We report a case of Alagille syndrome (arteriohepatic dysplasia) with the unusual
      radiological abnormality of synostosis of the proximal portions of the radius and
      ulna bilaterally, a manifestation which, to our knowledge, has not previously
      been described in a specific patient in the English language literature. We also
      describe additional features of the syndrome in the same patient and review the
      published literature on radiological manifestations of this condition.

PMID- 12802523
TI  - Familial occurrence of osteoid osteoma.
AB  - Familial occurrence of osteoid osteoma is an exceedingly rare event. This paper
      describes the second report of this event, where two siblings presented with this
      lesion in the same location, the proximal left femur. They both presented at 6
      years of age, but 3 years apart.

PMID- 12802524
TI  - Water-lily sign on MR imaging of primary intramuscular hydatidosis of sartorius
      muscle.
AB  - Primary hydatidosis of muscle is very rare and can cause a variety of diagnostic
      problems, especially in the absence of typical radiologic findings. This is the
      report of a case of primary intramuscular hydatid cyst in a 35-year-old woman,
      who presented with a 1-year history of a painless lump in the distal left thigh.
      The authors document the pathognomonic water-lily sign that has not previously
      been reported in a case of intramuscular hydatid disease.

PMID- 12802525
TI  - Characteristics of fungal phytases from Aspergillus fumigatus and Sartorya
      fumigata.
AB  - Aspergillus fumigatus phytase has previously been identified as a phytase with a
      series of favourable properties that may be relevant in animal and human
      nutrition, both for maximising phytic acid degradation and for increasing mineral
      and amino acid availability. To study the natural variability in amino acid
      sequence and its impact on the catalytic properties of the enzyme, we cloned and
      overexpressed the phytase genes and proteins from six new purported A. fumigatus
      isolates. Five of these phytases displayed < or= 2 amino acid substitutions and
      had virtually identical stability and catalytic properties when compared with the
      previously described A. fumigatus ATCC 13073 phytase. In contrast, the phytase
      from isolate ATCC 32239 ( Sartorya fumigata, the anamorph of which was identified
      as A. fumigatus) was more divergent (only 86% amino acid sequence identity), had
      a higher specific activity with phytic acid, and displayed distinct differences
      in substrate specificity and pH-activity profile. Finally, comparative
      experiments confirmed the favourable stability and catalytic properties of A.
      fumigatus phytase.

PMID- 12802526
TI  - The challenge of multidrug resistance: actual strategies in the development of
      novel antibacterials.
AB  - Bacterial resistance against established antibiotics is becoming an increasingly
      important global healthcare problem. Despite enormous efforts, the number of
      therapeutically useful compounds that emerge from chemical derivatisation
      programs, which aim at circumventing mechanisms of resistance, is continuously
      decreasing and no truly novel class of compound has been introduced into therapy
      for nearly four decades. Hopes are now set on a thorough elucidation of bacterial
      cell functions to identify new bacterial target sites, and on the development of
      novel compounds with alternative modes of action. The pursuit of these strategies
      is rendered possible by employment of biotechnologically based methods such as in
      vivo modification of biosynthetic routes in antibiotic-producing organisms, large
      scale screening assays with isolated bacterial targets, the molecular profiling
      of bacterial genomes and proteomes, and the development and clinical use of
      biochips as diagnostic tools for rapid identification and characterization of
      pathogenic strains. As one of the most promising class of compounds known to date
      with unique modes of action that escape most known mechanisms of resistance,
      peptic agents have recently came under the focus of anti-infective research, just
      as extracellular signalling molecules (autoinducer) have emerged as new bacterial
      target sites.

PMID- 12802527
TI  - Biosynthesis of fructo-oligosaccharides by Sporotrichum thermophile during
      submerged batch cultivation in high sucrose media.
AB  - Biosynthesis of fructo-oligosaccharides (FOS) was observed during growth of the
      thermophilic fungus Sporotrichum thermophile on media containing high sucrose
      concentrations. Submerged batch cultivation with the optimum initial sucrose
      concentration of 250 g/l allowed the production of 12.5 g FOS/l. The FOS mixture
      obtained was composed of three sugars, which were isolated by size-exclusion
      chromatography. They were characterized by acid hydrolysis and HPLC as 1-kestose,
      6-kestose and neokestose. The mechanism of osmotic adaptation of S. thermophile
      was investigated and sugars and amino acids were found to be the predominant
      compatible solutes. The fungus accumulated glutamic acid, arginine, alanine,
      leucine and lysine, in order to balance the outer osmotic pressure. Fatty acid
      analysis of the membrane lipids showed a relatively high percentage of
      unsaturated lipids, which is known to be associated with high membrane fluidity.

PMID- 12802528
TI  - A chitinase with high activity toward partially N-acetylated chitosan from a new,
      moderately thermophilic, chitin-degrading bacterium, Ralstonia sp. A-471.
AB  - A moderately thermophilic bacterium, strain A-471, capable of degrading chitin
      was isolated from a composting system of chitin-containing waste. Analysis of the
      16S rDNA sequence revealed that the bacterium belongs to the genus Ralstonia. A
      thermostable chitinase A ( Ra-ChiA) was purified from culture fluid of the
      bacterium grown in colloidal chitin medium. Purification of the enzyme was
      achieved mainly by exploiting its binding to the colloidal chitin. The molecular
      mass of the enzyme was estimated to be 70 kDa and the isoelectric point
      approximately 4.7. N-terminal amino acid sequencing revealed a sequence of
      ADPYLKVAYYP, which had high homology (66% identity) with that of chitinase A1
      from Bacillus circulans WL-12. The pH and temperature optima were determined to
      be 5.0 and 70 degrees C, respectively. The enzyme was classified as a retaining
      glycosyl hydrolase and was most active against partially N-acetylated chitosans.
      Its activities towards the partially N-acetylated chitosans, i.e. chitosan 7B,
      chitosan 8B, and chitosan 9B, were about 11-fold, 9-fold, and 5-fold higher than
      towards colloidal chitin, respectively. Ra-ChiA cleaved (GlcNAc)6 almost
      exclusively into (GlcNAc)2. Activation of Ra-ChiA was observed by the addition of
      1 mM Cu2+, Mn2+, Ca2+, or Mg2+. Degradation of the partially N-acetylated
      chitosan produced oligosaccharides with a degree of polymerization ranging from 1
      8; these are products that offer potential application for functional
      oligosaccharide production.

PMID- 12802529
TI  - Exudate gums: occurrence, production, and applications.
AB  - This paper presents a review of the industrially most relevant exudate gums: gum
      arabic, gum karya, and gum tragacanth. Exudate gums are obtained as the natural
      exudates of different tree species and exhibit unique properties in a wide
      variety of applications. This review covers the chemical structure, occurrence
      and production of the different gums. It also deals with the size and relative
      importance of the various players on the world market. Furthermore, it gives an
      overview of the main application fields of the different gums, both food and non
      food.

PMID- 12802530
TI  - Screening of tetrachlorodibenzo- p-dioxin-degrading fungi capable of producing
      extracellular peroxidases under various conditions.
AB  - Forty-six pulp-bleaching fungi were screened for production of key enzymes for
      conversion of polychlorinated dibenzo-p-dioxins--lignin peroxidase (LiP),
      manganese peroxidase (MnP), and manganese-independent peroxidase (MiP)--under
      various conditions that would allow their utilization in the environment. Of 38
      MnP-producing strains with MiP activity, 22 produced LiP. Three of the new
      isolates, Bjerkandera sp. strains MS191, MS325, and MS1167, were the best
      producers of the three different peroxidases, and had reasonable growth rates.
      The most promising Bjerkandera sp. strain, MS325, exhibited significant levels of
      LiP and MnP activities under various conditions, e.g., nutrient nitrogen
      sufficient or -limited conditions, conditions with or without Mn(II), and changes
      in temperature (15-37 degrees C). Furthermore, the ability of this strain to
      degrade 1,3,6,8-tetrachlorodibenzo- p-dioxin was confirmed. The results presented
      here indicate that utilization of Bjerkandera sp. strain MS325 on a practical
      scale in the environment has several advantages over many white rot fungi, which
      produce extracellular peroxidases only under specific conditions such as nutrient
      limitation.

PMID- 12802532
TI  - Changes in structure, activity and metabolism of aerobic granules as a microbial
      response to high phenol loading.
AB  - Four column-type sequential aerobic sludge blanket reactors were fed with phenol
      as the sole carbon and energy source and operated at loading rates of 1.0, 1.5,
      2.0 and 2.5 kg phenol m(-3) day(-1). The results indicated that phenol loading
      exerted a profound influence on the structure, activity and metabolism of the
      aerobic granules. Compact granules with good settling ability were maintained at
      loadings up to 2.0 kg phenol m(-3) day(-1), and structurally weakened granules
      with enhanced production of extracellular polymers and proteins and significantly
      lower hydrophobicities were observed at the highest loading of 2.5 kg phenol m(
      3) day(-1). Specific oxygen uptake rate, catechol 2,3-dioxygenase (C23O) and
      catechol 1,2-dioxygenase (C12O) activities peaked at a loading of 2.0 kg phenol
      m(-3) day(-1), and declined thereafter. Granules degraded phenol completely in
      all four reactors, mainly through the meta cleavage pathway as C23O activities
      were significantly higher than C12O activities. At the highest loading applied,
      the anabolism and catabolism of microorganisms were regulated such that phenol
      degradation proceeded exclusively via the meta pathway, apparently to produce
      more energy for overstimulation of protein production against phenol toxicity.
      This work contributes to a better understanding of the ability of aerobic
      granules to handle high-strength industrial wastewaters containing chemicals that
      are normally inhibitory to microbial growth.

PMID- 12802531
TI  - Metabolic flux analysis of pykF gene knockout Escherichia coli based on 13C
      labeling experiments together with measurements of enzyme activities and
      intracellular metabolite concentrations.
AB  - Metabolic flux analysis based on 13C-labeling experiments followed by the
      measurement of intracellular isotope distribution using both 2D NMR and GC-MS was
      carried out to investigate the effect of pyruvate kinase (pyk) gene knockout on
      the metabolism of Escherichia coli in continuous culture. In addition, the
      activities of 16 enzymes, and the concentrations of 5 intracellular metabolites,
      were measured as a function of time in batch culture as well as continuous
      culture. It was found that flux through phosphoenol pyruvate carboxylase and
      malic enzyme were up-regulated in the pykF- mutant as compared with the wild
      type, and acetate formation was significantly reduced in the mutant. In addition,
      flux through the phosphofructose kinase pathway was reduced and that through the
      oxidative pentose phosphate (PP) pathway increased in the mutant. This was
      evidenced by the corresponding enzyme activities, and the increase in the
      concentrations of phosphoenol pyruvate, glucose-6-phosphate and 6
      phosphogluconate, etc. It was also found for continuous cultivation that the
      enzyme activities of the oxidative PP and Entner-Doudoroff pathways increased as
      the dilution rate increased for the pykF- mutant. To clarify the metabolism
      quantitatively, it was found to be quite important to integrate the information
      on intracellular metabolic flux distribution, enzyme activities and intracellular
      metabolite concentrations.

PMID- 12802533
TI  - Development of a bisphenol A-adsorbing yeast by surface display of the
      Kluyveromyces yellow enzyme on Pichia pastoris.
AB  - A novel surface-engineered strain of yeast Pichia pastoris was constructed that
      displays at its surface Kluyveromyces lactis Yellow Enzyme (KYE) fused to the C
      terminal half of Saccharomyces cerevisiae alpha-agglutinin. The expression of the
      fusion protein was controlled by the AOX1-promoter. The new strain showed an
      increased sorption of the xenoestrogen Bisphenol A (BPA). It was shown that
      sorption of BPA depended on the presence of methanol in the growth medium and on
      the pH of the binding assays. The binding kinetics were typical for binding at a
      surface. The present results demonstrate that the alpha-agglutinin surface
      display system can be used in the yeast P. pastoris.

PMID- 12802534
TI  - Improved recovery of active recombinant laccase from maize seed.
AB  - Lignolytic enzymes such as laccase have been difficult to over-express in an
      active form. This paper describes the expression, characterization, and
      application of a fungal laccase in maize seed. The transgenic seed contains
      immobilized and extractable laccase. Fifty ppm dry weight of aqueously
      extractable laccase was obtained, and the remaining solids contained a
      significant amount of immobilized laccase that was active. Although a portion of
      the extractable laccase was produced as inactive apoenzyme, laccase activity was
      recovered by treatment with copper and chloride. In addition to allowing the
      apoenzyme to regain activity, treatment with copper also provided a partial
      purification step by precipitating other endogenous corn proteins while leaving
      >90% of the laccase in solution. The data also demonstrate the application of
      maize-produced laccase as a polymerization agent. The apparent concentration of
      laccase in ground, defatted corn germ is approximately 0.20% of dry weight.

PMID- 12802535
TI  - Lassoed liver.

PMID- 12802536
TI  - Cerebral manifestations, hemihypertrophy and lymphoedema of one leg in a child
      with epidermal nevus syndrome (Schimmelpenning-Feuerstein-Mims).
AB  - The report focuses on a rare variant form of epidermal nevus syndrome (ENS)
      (Schimmelpenning-Feuerstein-Mims syndrome) describing lesions involving the skin,
      eyes, skeleton, heart and brain in an 11-year-old boy. Despite his evident brain
      pathology, the boy lacks neurological symptoms and mental retardation. We
      describe his unusual MRI appearances and radiographic skeletal findings. To our
      knowledge this is the first report of ENS with lymphoedema occurring together in
      the same individual.

PMID- 12802537
TI  - The impact of bladder shape on the ultrasonographic measurement of bladder volume
      in children.
AB  - BACKGROUND: US is used for non-invasive assessment of bladder shape and for
      calculation of bladder volume. OBJECTIVE: To evaluate the impact of bladder shape
      on the accuracy of US estimation of bladder volume in children and to calculate
      formulas for US estimation of volume for different bladder shapes. MATERIALS AND
      METHODS: US was performed in 146 children (94 girls, 52 boys, age range 9 months
      to 17 years, median 7.9 years) referred for urodynamic investigation. Three
      bladder diameters were measured, and bladder shapes were categorized as round,
      ellipsoid, cuboid, triangular and undefined. Urine was collected, and total
      bladder volume calculated. Correction coefficients (k) were calculated for the
      whole sample and for each bladder shape using linear regression analysis.
      RESULTS: Round bladder shape was present in 23%, 25% showed a cuboid shape, 21%
      an ellipsoid shape, 25% a triangular shape, and 6% had an undefined shape.
      Correction (regression) coefficient (k) for the whole sample was 0.66 (SE =
      0.011); for round bladder 0.561 (SE = 0.013), cuboid bladder 0.923 (SE = 0.012),
      ellipsoid bladder 0.802 (SE = 0.006), triangular bladder 0.623 (SE = 0.007), and
      for undefined shape 0.749 (SE = 0.048). Mean percentage errors when using
      different correction coefficients were significantly lower than errors when using
      k = 0.5 applied to our data. CONCLUSIONS: Bladder shape has considerable impact
      on the accuracy of US estimation of bladder volume in children. Correction
      coefficients should be used for volume measurements of different bladder shapes.

PMID- 12802538
TI  - Abdominal ultrasonographic findings in patients with sickle-cell anaemia and
      thalassaemia intermedia.
AB  - BACKGROUND: The high prevalence and heterogeneity of clinical and haematological
      phenotypes of sickle-cell anaemia and thalassaemia intermedia (TI) syndromes in
      the Greek population constitute a major challenge in routine medical practice.
      PURPOSE: To investigate the spectrum and prevalence of abdominal US findings in
      these patients. MATERIALS AND METHODS: The study included 105 patients, 13
      homozygous for sickle-cell anaemia (S/S) and 92 with TI syndromes (Th/S,
      beta(thal)/beta(thal )or beta(thal)/deltabeta(thal)). The patients' ages ranged
      from 1 to 54 years, with 49 males and 56 females. RESULTS: At the time of the
      examination, 41% of the patients had undergone splenectomy and 23.8% had
      undergone cholecystectomy. The most frequent US findings (percentages refer to
      all patients) were: hepatomegaly (70.5%), splenomegaly (48.6%) and cholelithiasis
      (20%). A bright liver was identified in 3.8% and focal hepatic lesions were
      present in two patients of the TI group. Functional disorders of the gallbladder
      concerned mainly patients with sickle-cell syndromes. Of those with S/S, 30.8%
      had a shrunken spleen. An echogenic pancreas was identified in one patient in
      each group. Increased renal echogenicity was observed in 17.6% of patients with
      sickle-cell syndromes. One case of polycystic kidney disease was diagnosed and
      coexisted with S/S. CONCLUSIONS: The value of US imaging in detecting
      complications of sickle-cell and TI syndromes is still debated. To our knowledge,
      there are no previous reports concerning the frequency and spectrum of abdominal
      US findings in patients with these syndromes.

PMID- 12802539
TI  - Thoracic malignant peripheral nerve sheath tumour mimicking a pleural tumour: a
      rare pedunculated appearance.
AB  - A malignant peripheral nerve sheath tumour (MPNST) generally occurs in adults and
      often in patients with neurofibromatosis-1 (NF-1). We present a rare case of a
      huge thoracic MPNST arising from the intercostal nerve in a 12-year-old girl
      without NF-1. In addition to the unusual occurrence in a child without NF-1, MRI
      demonstrated a unique pedunculated appearance mimicking a pleural tumour. In this
      report, we present the CT and MRI findings of our case, together with the
      histopathological findings, and review previous reports.

PMID- 12802540
TI  - Moyamoya disease in a child with previous acute necrotizing encephalopathy.
AB  - A previously healthy 24-day-old boy presented with a 2-day history of fever and
      had a convulsion on the day of admission. MRI showed abnormal signal in the
      thalami, caudate nuclei and central white matter. Acute necrotising
      encephalopathy was diagnosed, other causes having been excluded after biochemical
      and haematological analysis of blood, urine and CSF. He recovered, but with
      spastic quadriparesis. At the age of 28 months, he suffered sudden deterioration
      of consciousness and motor weakness of his right limbs. MRI was consistent with
      an acute cerebrovascular accident. Angiography showed bilateral middle cerebral
      artery stenosis or frank occlusion with numerous lenticulostriate collateral
      vessels consistent with moyamoya disease.

PMID- 12802541
TI  - The use of silver nitrate for chemical de-epithelialization and urothelialization
      of intestine in a rabbit model of augmentation cystoplasty.
AB  - Urinary tract reconstruction using bowel segments can result in complications
      such as electrolyte abnormalities, infections, stones and cancer. Intestinal
      mucosa is the primary site responsible for these complications. De
      epithelialization of the mucosa and subsequent urothelialization might alleviate
      these problems. We recently reported our success in de-epithelialization and
      subsequent uroepithelialization of intestinal segments using 10 g/100 ml AgNO(3)
      solution in a rat model of augmentation. In this study, chemical de
      epithelialization of a colonic segment was attempted using 10 g/100 ml AgNO(3)
      solution in a rabbit model of augmentation. Sigmoid cystoplasty was performed in
      20 male New Zealand rabbits using a 6 cm patch of sigmoid colon. There were two
      groups, including one group of five rabbits (control, group 1) that underwent
      augmentation alone, while another group (15 rabbits, treatment group or group 2)
      was treated with 10 g/100 ml AgNO(3 )solution before augmentation. Control
      rabbits were killed at the week 8 of experimentation. Treatment rabbits were
      killed at 2-, 4-, 6- and 8-week intervals. Immediately before augmentation and at
      the end of the 8 week experimental period each rabbit underwent cystometry. De
      epithelialization of the bowel epithelium without urothelialization was apparent
      in the treatment rabbits killed at 2 and 4 weeks. Histological analysis revealed
      almost complete urothelialization of the augmented sections treated with 10 g/100
      ml AgNO(3 )solution at the end of the 6 and 8 week of experimental periods. The
      preoperative and postoperative bladder capacities increased substantially in all
      groups. There was no obvious histologic difference in the amount of collagen
      present in the augmented tissues in any of the experimental groups. The present
      study confirmed that the treatment of intestinal segments with 10 g/100 ml AgNO(3
      )solution led to chemical de-epithelialization and urothelialization of the
      augmented segments. This procedure could, theoretically, have applications to
      human surgery.

PMID- 12802542
TI  - Immunocytochemical distribution of nitric oxide synthase in the human seminal
      vesicle: a light and electron microscopical study.
AB  - Although nitric oxide (NO) has been proven to be one of the most important non
      adrenergic, non-cholinergic mediators in the control of human reproductive tract
      organs, to date information on the significance of NO-mediated signal
      transduction in the control of human seminal vesicle (SV) function is still
      sparse.()Recent investigations have underlined the significance of NO in the
      maintenance of sperm capacitation and viscosity of the seminal plasma as well as
      in the control of mammalian seminal vesicle smooth muscle tone. In order to
      further investigate the functional impact of NO on the regulation of normal SV
      function, we examined the distribution of NADPH-diaphorase (NADPH-d), endothelial
      nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in the
      cellular anatomy of human SV by means of light and electron microscopical
      immunocytochemistry (LM, EM) in combination with the tyramide signal
      amplification technique. Human SV were obtained from 15 patients who had
      undergone surgery for pelvic malignancies (carcinoma of the prostate or urinary
      bladder). SV specimens were fixed, sectioned and examined by LM and EM for the
      presence of NAPDH-d, eNOS and nNOS using specific antibodies and advanced
      staining procedures. LM revealed a dense NADPH-d reaction in glandular epithelial
      structures, whereas no substantial labeling was detected in the fibromuscular
      stroma. EM showed that the NADPH-d reaction product was abundantly detectable
      attached to membranes of the endoplasmic reticulum, mitochondria and the nuclei
      of glandular epithelial cells. nNOS staining was found in nerve fibers branching
      within the SV tissue. eNOS staining was present in small vessels but was only
      observed to a minor degree in glandular and subglandular structures and the
      smooth muscle stroma. Our results support the hypothesis that human SV is a site
      of NO production. The distribution of NADPH-d may give rise to the speculation
      that NO is mainly involved in the regulation of SV secretory activity. The sparse
      correlation between NADPH-d-, eNOS- and nNOS-staining might hint at the existence
      of a previously unidentified NOS isoform in human SV.

PMID- 12802543
TI  - Spiral versus J-shaped coils for neurovascular embolisation-an in-vitro study.
AB  - Our purpose was to compare the characteristics of J-shaped detachable platinum
      coils with those of spiral coils in in-vitro vascular models. J-shaped coils
      consist of distal semicircular and proximal straight segments, the latter
      extending for most of the length of the coil. Spiral coils have a helical shape
      memory and are thus limited in expansion. In in-vitro silicone vascular models
      simulating intracranial aneurysms and dural arteriovenous fistulae, we compared J
      shaped and spiral coils with regard to ease of delivery, anchoring and folding
      patterns, and stability in various types of vascular lumen. Delivery and
      retrieval were comparable. In large and irregular aneurysms and venous sinuses, J
      shaped coils could form a more complex basket which conformed to the shape of the
      vascular cavity. The J-shaped coil was always in contact with the vessel wall. In
      wide-necked aneurysms, coil protrusion was more frequent with J-shaped coils,
      while spiral coils tended to stay compact and circular. Arteries were occluded in
      a shorter segment with spiral coils. J-shaped coils were safe and superior for
      large and irregular aneurysms or sinuses. Spiral coils were preferable for
      spherical aneurysms and segmental occlusion of arteries.

PMID- 12802544
TI  - Zonal frequency analysis of infarct extent. Part II: anterior and posterior
      cerebral artery infarctions.
AB  - The object of the study was to test the hypotheses that analysis of the anatomic
      zones affected by single anterior (A), posterior (P), and middle (M) cerebral
      artery (CA) infarcts, and by dual- and triple-vessel infarcts, will disclose (i)
      sites most frequently involved by each infarct type (peak sites), (ii) sites most
      frequently injured by multiple different infarct types (vulnerable zones), and
      (iii) anatomically overlapping sites in which the relative infarct frequency
      becomes equal for two or more different infarct types and/or in which infarct
      frequency shifts greatly between single and multivessel infarcts (potential
      border zones). Precise definitions of each vascular territory were adopted. CT
      and MRI studies from 20 ACA, 20 PCA, three dual ACA-PCA, and four triple ACA-PCA
      MCA infarcts were mapped onto a standard template (Part I). Relative infarct
      frequencies in each zone were analyzed within and across infarct types to
      identify the centers and peripheries of each infarct type, the zones most
      frequently affected by multiple different infarct types, the zones where relative
      infarct frequency was equal for different infarcts, and the zones where infarct
      frequency shifted markedly from single- to multiple-vessel infarcts. Zonal
      frequency analysis provided quantitative data on the relative infarct frequency
      in each anatomic zone for each infarct type. It displayed zones of peak infarct
      frequency for each infarct, zones more vulnerable to diverse types of infarct,
      peripheral "overlap" zones of equal infarct frequency, and zones where infarct
      frequency shifted markedly between single- and multiple-vessel infarcts. It is
      concluded that the hypotheses are correct.

PMID- 12802545
TI  - High-resolution 3D T2-weighted fast spin echo: new applications in the orbit.
AB  - Recent developments have made available for ophthalmologic MR imaging a very high
      resolution 3D fast spin echo T2 (3D FSE T2) sequence, which runs in a standard
      head coil. A modification of this technique, 3D FSEz T2, uses a zero-filled slice
      interpolation method during post-processing to further improve spatial
      resolution. We describe the technique and share our early clinical observations
      in patients with ocular masses. Briefly, the additional information from the 3D
      FSEz T2 resulted in a change in diagnosis from the conventional imaging series in
      11 of (41%) 27 studies, usually through the identification of previously treated
      retinoblastoma lesions. The new sequence significantly increased diagnostic
      confidence in six (38%) of the remaining 16 cases, usually through better
      anatomical detail and lesion conspicuity, and did not change interpretation in 10
      cases. Such an approach improves diagnostic confidence and may eliminate the need
      for a dedicated surface coil examination.

PMID- 12802546
TI  - Embolisation of intracranial meningiomas without subsequent surgery.
AB  - In an open, prospective study, we embolised intracranial meningiomas in seven
      patients, without subsequent surgery. Follow-up over a mean of 20 months included
      serial neurological examination, MRI and MR spectroscopy. Clinically,
      embolisation had no adverse effects. Symptomatic patients showed clinical
      improvement. On MRI marked tumour shrinkage occurred after embolisation in six
      patients, and was most pronounced during the first 6 months. In a young boy the
      tumour was unchanged despite complete angiographic devascularisation.
      Embolisation without subsequent surgery may cause substantial tumour shrinkage
      and thus be used in selected in patients. However, thorough follow-up is
      mandatory to ascertain the effects of embolisation.

PMID- 12802547
TI  - Comparison of contrast-enhanced T1-weighted and 3D constructive interference in
      steady state images for predicting outcome after hearing-preservation surgery for
      vestibular schwannoma.
AB  - We compared contrast-enhanced T1-weighted and 3D constructive interference in
      steady state (CISS) sequences for demonstrating possible prognostic factors in
      hearing-preservation surgery for vestibular schwannoma. We studied 22 patients
      with vestibular schwannomas having hearing-preservation surgery. Postoperatively
      six (27%) had a facial palsy and eight (36%) had hearing loss. There was a
      significant correlation between the size of the tumour and facial palsy (r=
      0.72). Both techniques adequately demonstrated all tumours. Involvement of the
      fundus of the internal auditory canal (IAC) and a small distance between the
      lateral border of the tumour and the fundus were correlated significantly with
      hearing loss (r=-0.81 and -0.75, respectively). The 3D-CISS sequence, by virtue
      of its high contrast resolution was superior to T1-weighted images ( P<0.05) for
      detection of the fundal involvement. The direction of displacement of the facial
      nerve did not correlate with facial palsy or hearing loss. We think that 3D-CISS
      images better show the features influencing surgical outcome, but that contrast
      enhanced T1-weighted images are required for diagnosis.

PMID- 12802549
TI  - The broken escalator phenomenon. Aftereffect of walking onto a moving platform.
AB  - We investigated the physiological basis of the 'broken escalator phenomenon',
      namely the sensation that when walking onto an escalator which is stationary one
      experiences an odd sensation of imbalance, despite full awareness that the
      escalator is not going to move. The experimental moving surface was provided by a
      linear motor-powered sled, moving at 1.2 m/s. Sled velocity, trunk position,
      trunk angular velocity, EMG of the ankle flexors-extensors and foot-contact
      signals were recorded in 14 normal subjects. The experiments involved, initially,
      walking onto the stationary sled (condition Before). Then, subjects walked 20
      times onto the moving sled (condition Moving), and it was noted that they
      increased their walking velocity from a baseline of 0.60 m/s to 0.90 m/s. After
      the moving trials, subjects were unequivocally warned that the platform would no
      longer move and asked to walk onto the stationary sled again (condition After).
      It was found that, despite this warning, subjects walked onto the stationary
      platform inappropriately fast (0.71 m/s), experienced a large overshoot of the
      trunk and displayed increased leg electromyographic (EMG) activity. Subjects were
      surprised by their own behaviour and subjectively reported that the 'broken
      escalator phenomenon', as experienced in urban life, felt similar to the
      experiment. By the second trial, most movement parameters had returned to
      baseline values. The findings represent a motor aftereffect of walking onto a
      moving platform that occurs despite full knowledge of the changing context. As
      such, it demonstrates dissociation between the declarative and procedural systems
      in the CNS. Since gait velocity was raised before foot-sled contact, the findings
      are at least partly explained by open-loop, predictive behaviour. A cautious
      strategy of limb stiffness was not responsible for the aftereffect, as revealed
      by no increase in muscle cocontraction. The observed aftereffect is unlike others
      previously reported in the literature, which occur only after prolonged
      continuous exposure to a sensory mismatch, large numbers of learning trials or
      unpredictable catch trials. The relative ease with which the aftereffect was
      induced suggests that locomotor adaptation may be more impervious to cognitive
      control than other types of motor learning.

PMID- 12802550
TI  - Effect of target-distractor similarity on FEF visual selection in the absence of
      the target.
AB  - We tested the hypothesis that frontal eye field (FEF) visual activity integrates
      visual information with a template of a target by examining whether a target that
      is not present in a search display influences the target selection in FEF. Neural
      activity was recorded in FEF of macaque monkeys performing visual search for a
      singleton target defined by color or direction of motion. The target remained
      constant throughout, but not across experimental sessions. Trials with
      distractors dissimilar to the target were interleaved with trials with
      distractors similar to the target. The hypothesis was tested by measuring the
      magnitude of activity in randomly interleaved trials with the target absent and
      only distractors in the display. We found that the response to the distractors
      was significantly greater when presented with displays consisting of distractors
      that resembled the absent target than when presented with displays consisting of
      distractors most different from the absent target. The influence of target
      distractor similarity on FEF activity was also observed when the target was
      present, as reported previously. These data suggest that a template of the absent
      target can influence the selection process in FEF. This provides more direct
      evidence that FEF integrates visual information and knowledge of the target to
      determine the goal of a saccade.

PMID- 12802551
TI  - Interactions between inputs from adjacent digits in somatosensory thalamus and
      cortex of the raccoon.
AB  - Interactions between somatosensory afferents arriving from different points in
      the periphery play an important role in sensory discrimination and also provide
      the substrate for plasticity following peripheral injury. To examine the extent
      and time course of such interactions, extracellular recordings were made from
      neurons in the primary somatosensory cortex and the ventroposterior lateral
      thalamus of anesthetized raccoons. Interactions between adjacent digits were
      studied using the conditioning-test paradigm in which a test pulse was delivered
      to the digit containing the neuron's receptive field (the on-focus digit) at
      various intervals following conditioning stimulation of an adjacent, off-focus
      digit. Off-focus stimulation produced predominantly inhibition of the test
      response with a maximum effect at 20-40 ms in both cortex and thalamus. The mean
      inhibition was approximately twice as large in the thalamus as in the cortex.
      Recordings were made in other animals after unmyelinated C fibers had been
      destroyed in the on-focus digit by subcutaneous injection of capsaicin. This
      resulted in a doubling of the responses evoked by the test stimulus in both
      regions, but the spontaneous discharge rate was not changed. The amount of
      inhibition produced in the cortex was unchanged by capsaicin treatment, but was
      reduced in the thalamus compared to control animals. This indicates that
      capsaicin-sensitive peripheral afferents provide a tonic control over interdigit
      inhibition in the thalamus.

PMID- 12802552
TI  - Abducens conditioning in in vitro turtle brain stem without cerebellum requires
      NMDA receptors and involves upregulation of GluR4-containing AMPA receptors.
AB  - Previous work showed that in vitro abducens eyeblink classical conditioning of
      turtle brain stem-cerebellum preparations involved NMDA-mediated mechanisms and
      redistribution of GluR4-containing AMPA receptors in the abducens motor nuclei.
      Since conditioning can be obtained in brain stem preparations without the
      cerebellum, we examined whether similar mechanisms were involved during
      conditioning of the brain stem alone. The results showed that conditioning could
      not be induced in the presence of the NMDA receptor antagonist dl-2-amino-5
      phosphonovaleric acid (AP-5) and that abducens nerve conditioned responses, once
      initiated in normal saline, were significantly attenuated in the presence of AP
      5. The effects of AP-5 did not generally depress physiological responsiveness of
      preparations because some abducens nerve reflexes were not significantly reduced
      by the compound. GluR4-containing AMPA receptors in the abducens motor nuclei
      were significantly upregulated and positively correlated with the levels of
      conditioning similar to that of preparations having an intact cerebellum.
      Furthermore, increased GluR4 subunits after brain stem conditioning was confirmed
      by Western blot analysis. These results suggest that NMDA receptor-mediated
      mechanisms and GluR4 upregulation may mediate in vitro abducens eyeblink
      classical conditioning and that these mechanisms reside in the brain stem
      eyeblink circuitry.

PMID- 12802553
TI  - Two phases of short-interval intracortical inhibition.
AB  - Short-interval intracortical inhibition (SICI) is a widely used method to study
      cortical inhibition, and abnormalities have been found in several neurological
      and psychiatric disorders. Previous studies suggested that SICI involves two
      phases and the first phase may be explained by axonal refractoriness. Our
      objectives are to further investigate the mechanisms of the two phases of SICI.
      SICI was studied in 11 normal volunteers by a paired transcranial magnetic
      stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold
      conditioning stimulus (80% resting motor threshold for rest condition and 95%
      active motor threshold for active condition) followed by a suprathreshold test
      stimulus at interstimulus intervals (ISIs) of 1-4.5 ms in steps of 0.5 ms. Motor
      evoked potentials (MEPs) were recorded from the right first dorsal interosseous
      muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and
      4 mV MEPs at rest were studied with the target muscle relaxed and during 20%
      maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms
      for the rest condition and the difference among ISIs was reduced with voluntary
      contraction. SICI increased with larger test MEP amplitude and decreased with
      voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation
      and this is likely related to short-interval intracortical facilitation. For rest
      SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than
      from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI
      at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and
      2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully
      explained by axonal refractoriness and synaptic inhibition may be involved. SICI
      is a complex phenomenon and inhibition at different ISIs may be mediated by
      different inhibitory circuits.

PMID- 12802554
TI  - Multitasking costs in close-head injury patients. A fine-grained analysis.
AB  - The issue of whether severe close-head injury (CHI) patients suffer from
      disproportionate dual-task deficits compared with matched controls was
      investigated in two experiments. In the first experiment, either one or three
      masked letters were presented at the center of a monitor, followed by a pure tone
      at variable stimulus-onset asynchronies (SOAs). In half of the blocks of trials,
      the task on the letters required a delayed report of the letters at the end of
      each trial; in the other half of the blocks, the letters had to be ignored. The
      tone task always required an immediate manual response based on the tone pitch.
      In the second experiment, either three masked letters or three masked digits were
      presented with equal probability in each trial, followed by a tone at variable
      SOAs. The task required the delayed report of the characters only if they were
      letters, or ignoring the characters if they were digits. In both experiments, CHI
      patients and matched controls both exhibited an SOA-locked slowing of the
      reaction time (RT) to the tone: When characters had to be encoded for delayed
      report, tone RT increased progressively as SOA was decreased. The SOA effect on
      tone RT was more pronounced for CHI patients than for controls, suggesting that a
      substantial component of the slower processing time for CHI patients was related
      to a selective increase at a central stage of processing shared by the two tasks.
      Implications for models of the CHI effects on human performance are discussed.

PMID- 12802555
TI  - Bilateral impact of unilateral visual cortex lesions on the superior colliculus.
AB  - We examined the functional impact of a long-standing, unilateral primary visual
      cortex lesion on the superior colliculus (SC) using radiolabeled 2-deoxyglucose
      (2DG) as a marker of neural activity. In accord with known corticotectal
      connectivity and functional influence, 2DG uptake in the superficial layers of
      the ipsilesional SC was decreased. We also found a decrease in the superficial
      layers of the contralesional SC. These data suggest that modifications in
      activity in one SC can have a substantial influence on activity in its
      contralateral partner, and that processing in one visual hemifield does not occur
      independently of processing of signals in the opposite hemifield. The effects are
      not mediated by the contralateral hemisphere but are probably mediated by
      intercollicular circuitry.

PMID- 12802556
TI  - 'Side-effects': intrinsic and task-induced asymmetry in bimanual rhythmic
      coordination.
AB  - Multifrequency coordination studies have shown the importance of hand-role in
      addition to hand-preference in bimanual rhythmic coordination. In these studies,
      hand-role has been defined by the task of the individual hands (moving fast or
      slow). In the present study, the hands were coordinated at the same frequency and
      hand-role was defined by the asymmetry of the coordination pattern. Eleven
      consistent left-handers and 13 consistent right-handers tapped three patterns
      (anti-phase, left-gallop, right-gallop) in four visual feedback conditions (no
      feedback, left-hand feedback, right-hand feedback, full feedback). The analysis
      focused on phase shifts, phase variability, intertap interval variability, and
      correlations between intertap intervals. The manipulation of visual feedback had
      only minor effects. In the anti-phase pattern, a symmetric coupling mechanism was
      found. The results support the idea that coordination in the gallop pattern is
      governed by a hierarchical control mechanism. In contrast to the multifrequency
      studies, however, successful control in the gallop is not dependent on a hand
      arrangement that accommodates the preferred hand as the leading hand. An
      adjustment to the model of Summers et al. (1993, J Exp Psychol Hum Percept
      Perform 19:416-428) is presented for the case of the gallop pattern.

PMID- 12802557
TI  - Automated coupling of capillary-HPLC to matrix-assisted laser
      desorption/ionization mass spectrometry for the analysis of small molecules
      utilizing a reactive matrix.
AB  - This study describes the application of a novel, reactive matrix for the mass
      spectral analysis of steroids by capillary-high performance liquid chromatography
      (capillary-HPLC) coupled to matrix-assisted laser desorption/ionization (MALDI).
      The mass spectral analysis of steroids was accomplished after fully automated
      peak deposition of chromatographic peaks onto MALDI targets. The seven
      corticosteroids used as test compounds were: triamcinolone, prednisone,
      cortisone, fludrocortisone, dexamethasone, deoxycorticosterone, and budesonide.
      They were separated using a PepMap C(18) (3 microm particle size, 100 A pore
      width) column at five different concentration levels of 25, 15, 7.5, 2.5 and 1
      ng/microL, and the peaks were detected at a wavelength of 237 nm. The column
      effluent was mixed with 2,4-dinitrophenylhydrazine (DNPH) directly following the
      UV detector. The chromatographic peaks were then deposited onto the MALDI target
      with a robotic micro-fraction collector triggered by the UV detector signals. A
      special hydrophobic surface coating allowed the deposition of up to 4 microL (up
      to 90 % of the chromatographic peak volume) onto one sample spot. The compounds
      were then identified by MALDI mass spectrometry. Depending on the nature of the
      analyte, radical cations ([M](+.)) and sodium adduct ions ([M+Na](+)) of the
      steroids as well as protonated steroid-dinitrophenylhydrazone derivatives
      ([M(D)+H](+)) were detected in positive ion mode. The detection limits were
      between 0.5 and 15 ng injected with capillary-HPLC-MALDI-TOF-MS and between 0.3
      and 3 ng on target with MALDI-TOF when deposited manually.

PMID- 12802559
TI  - Amperometric biosensor with HRP immobilized on a sandwiched nano-Au / polymerized
      m-phenylenediamine film and ferrocene mediator.
AB  - An amperometric biosensor has been developed for the determination of H(2)O(2) in
      plant samples. Horseradish peroxidase (HRP) is immobilized on a sandwiched nano
      Au particle / m-phenylenediamine polymer film by glutaraldehyde cross-linking.
      The film is formulated on the carbon paste electrode (CPE) blended with ferrocene
      as an electron transfer mediator. On the low concentration range, the current
      response is related to the H(2)O(2) concentration linearly from 0 to 8x10(-6) M
      with a detection limit of 1.3x10(-7) M. On a wider concentration range of 8x10(
      6) to 1.4x10(-4) M, the reciprocal of current response is linearly related to the
      reciprocal of H(2)O(2) concentration. The apparent Michaelis-Menten constant
      (K(m)(app)) was calculated to be 0.0334 mM. The sensor has been tested by
      determining H(2)O(2) concentration in plant leaf samples.

PMID- 12802560
TI  - Comparison of alternative and conventional extraction techniques for the
      determination of zearalenone in corn.
AB  - Naturally contaminated corn samples of different origin were extracted using two
      conventional techniques (blending and shaking) and three alternative approaches
      (ultrasonic extraction, accelerated solvent extraction, and microwave-assisted
      extraction). Use of the same extraction mixture for all trials enabled the
      efficiency of the various extraction techniques to be compared. Extracts were
      filtered and directly analyzed by LC-ESI-MS, without further clean-up. The yield
      from the alternative extraction techniques showed efficiency to be higher than
      for conventional techniques. In particular, microwave-assisted extraction was
      slightly superior to other techniques.

PMID- 12802561
TI  - Application of time-resolved in-situ X-ray absorption spectroscopy in solid-state
      chemistry.
AB  - Time-resolved X-ray absorption spectroscopy (TR-XAS) possesses excellent
      capabilities to reveal quantitative phase composition and average valence
      together with the evolution of the local structure of a system under dynamic
      reaction conditions. The work discussed here focused on time-resolved in-situ XAS
      investigations aiming, first, at understanding structural evolution under dynamic
      conditions and, second, at revealing properties of the system studied not
      available from investigations under stationary conditions. Hence, not only was
      the local structure of a material studied under reaction conditions, but
      characteristic properties of the reaction, such as reaction intermediates or the
      kinetics of the reaction, were also elucidated. The solid-gas reactions presented
      here clearly demonstrate the potential of TR-XAS investigations to extend the
      suitability of XAS for in-situ studies in solid-state chemistry to investigations
      under dynamic conditions.

PMID- 12802562
TI  - Online SAXS investigations of polymeric hollow fibre membranes.
AB  - Polymeric membranes are used in industrial and analytical separation techniques.
      In this study small-angle X-ray scattering (SAXS) with synchrotron radiation has
      been applied for in-situ characterisation during formation of polymeric
      membranes. The spinning of a polyetherimide (PEI) hollow fibre membrane was
      chosen for investigation of dynamic aggregation processes during membrane
      formation, because it allows the measurement of the dynamic equilibrium at
      different distances from the spinning nozzle. With this system it is possible to
      resolve structural changes in the nm-size range which occur during membrane
      formation on the time-scale of milliseconds. Integral structural parameters, like
      radius of gyration and pair-distance distribution, were determined. Depending on
      the chosen spinning parameters, e.g. the flow ratio between polymer solution and
      coagulant water, significant changes in the scattering curves have been observed.
      The data are correlated with the distance from the spinning nozzle in order to
      get information about the kinetics of membrane formation which has fundamental
      influence on structure and properties of the membrane.

PMID- 12802564
TI  - Sustained modelling ability of artificial neural networks in the analysis of two
      pharmaceuticals (dextropropoxyphene and dipyrone) present in unequal
      concentrations.
AB  - An improvement is presented on the simultaneous determination of two active
      ingredients present in unequal concentrations in injections. The analysis was
      carried out with spectrophotometric data and non-linear multivariate calibration
      methods, in particular artificial neural networks (ANNs). The presence of non
      linearities caused by the major analyte concentrations which deviate from Beer's
      law was confirmed by plotting actual vs. predicted concentrations, and observing
      curvatures in the residuals for the estimated concentrations with linear methods.
      Mixtures of dextropropoxyphene and dipyrone have been analysed by using linear
      and non-linear partial least-squares (PLS and NPLSs) and ANNs. Notwithstanding
      the high degree of spectral overlap and the occurrence of non-linearities, rapid
      and simultaneous analysis has been achieved, with reasonably good accuracy and
      precision. A commercial sample was analysed by using the present methodology, and
      the obtained results show reasonably good agreement with those obtained by using
      high-performance liquid chromatography (HPLC) and a UV-spectrophotometric
      comparative methods.

PMID- 12802563
TI  - X-ray absorption spectroscopy to analyze nuclear geometry and electronic
      structure of biological metal centers--potential and questions examined with
      special focus on the tetra-nuclear manganese complex of oxygenic photosynthesis.
AB  - X-ray absorption spectroscopy (XAS) has become a prominent tool for the element
      specific analysis of transition metals at the catalytic center of metalloenzymes.
      In the present study the information content of X-ray spectra with respect to the
      nuclear geometry and, in particular, to the electronic structure of the protein
      bound metal ions is explored using the manganese complex of photosystem II
      (PSIII) as a model system. The EXAFS range carries direct information on the
      number and distances of ligands as well as on the chemical type of the ligand
      donor function. For first-sphere ligands and second-sphere metals (in
      multinuclear complexes), the determination of precise distances is mostly
      straightforward, whereas the determination of coordination numbers clearly
      requires more effort. The EXAFS section starts with an exemplifying discussion of
      a PSII spectrum data set with focus on the coordination number problem.
      Subsequently, the method of linear dichroism EXAFS spectroscopy is introduced and
      it is shown how the EXAFS data leads to an atomic resolution model for the tetra
      manganese complex of PSII. In the XANES section the following aspects are
      considered: (1) Alternative approaches are evaluated for determination of the
      metal-oxidation state by comparison with a series of model compounds. (2) The
      interpretation of XANES spectra in terms of molecular orbitals (MOs) is
      approached by comparative multiple-scattering calculations and MO calculations.
      (3) The underlying reasons for the oxidation-state dependence of the XANES
      spectra are explored. Furthermore, the potential of modern XANES theory is
      demonstrated by presenting first simulations of the dichroism in the XANES
      spectra of the PSII manganese complex.

PMID- 12802565
TI  - Recent synchrotron radiation microdiffraction experiments on polymer and
      biopolymer fibers.
AB  - The status of synchrotron radiation (SR) microdiffraction techniques developed at
      the ID13 beamline of the European Synchrotron Radiation Facility (ESRF) is
      reviewed for polymer and biopolymer fiber applications. Beam sizes in the
      micrometer-range have been used to study the local structure of whole fibers such
      as viscose-rayon or poly(p-phenylene terephthalamide). The possibilities for in
      situ studies during stretching, extrusion, or indentation will be discussed.

PMID- 12802566
TI  - Diamond paste-based electrodes for determination of Cr(III) in pharmaceutical
      compounds.
AB  - A new class of monocrystalline diamond paste-based electrodes is proposed for the
      determination of chromium(III) at trace levels in vitamins. Three types of
      monocrystalline diamond-natural diamond 1mu (natural diamond), synthetic diamond
      50mu (synthetic-1), and synthetic diamond 1mu (synthetic-2)-were used for
      electrode construction. The linear concentration ranges are between 10(-10) and
      10(-8); 10(-9) and 10(-7), and 10(-10) to 10(-8) mol L(-1), with limits of
      detection of 10(-12), 10(-12), and 10(-11) mol L(-1), when natural diamond,
      synthetic-1, and synthetic-2, respectively, are used as electrode materials. For
      electrodes based on natural diamond and synthetic-1 it was found that Cr(III)
      yields a peak at about +0.275+/-0.015 V (vs. Ag/AgCl) within a predetermined
      positive potential range situated between +0.4 and +0.2 V, while for the
      electrode based on synthetic-2 the peaks are found at +0.300+/-0.015 V (vs.
      Ag/AgCl). The proposed method is reliable for the determination of chromium(III)
      at trace levels in two vitamin tablets (RSD<0.2%).

PMID- 12802567
TI  - Chromatographic behavior of cadmium in an ion-pair reversed-phase micro HPLC
      system and its application to the determination of bio-available cadmium in soil
      samples.
AB  - A novel reversed phase ion-pair micro HPLC system with on-line fluorescence
      detection has been developed systematically and studied for the determination of
      cadmium in its bio-available fractions of soil samples. In this system, a micro
      ODS column of 1.0 mm i.d.x150 mm length and a mobile phase containing 6 mmol L(
      1) 8-hydroxyquinoline 5-sulphonic acid (HQS), 3 mmol L(-1) cetyltrimethylammonium
      bromide (CTMABr), 10 mmol L(-1) acetic acid-acetate buffer (pH 5.1) as well as
      50% acetonitrile at 50 microL min(-1) flow rate were employed to determine
      cadmium with a 2 microL flow cell through its fluorescence at 518 nm under 338 nm
      excitation. Furthermore, the composition of Cd-HQS chelate formed on the column
      was confirmed to be [Cd(HQS)(2)](2-) through a log-log plot method, and then
      combined with the ion-pair reagent by the electrostatic force under the
      chromatographic condition proposed. With such a method, the detection limit of
      cadmium was 8.48 ng mL(-1) (3sigma) with 1 microL sample injection, and the
      linear range for the determination of cadmium was 30-800 ng mL(-1) (R(2)=0.992).
      This method has been successfully applied to determination of cadmium in its bio
      available fractions of BCR-483 and soil samples without interference from other
      coexistent metal ions. The RSD (n=6) was less than 7.3%. The results were in
      agreement with the indicative value for BCR-483 and those for the soil samples
      obtained by ICP-MS with a pretreatment of bis(1,1,3,3-tetramethylbutyl)
      phosphinic acid extraction.

PMID- 12802568
TI  - Determination of low levels of free fibres of chrysotile in contaminated soils by
      X-ray diffraction and FTIR spectroscopy.
AB  - A new analytical method for the determination of low levels (0.01-1 wt%) of free
      fibres of chrysotile in contaminated clayey, sandy and sandy-organic soils is
      described. The detection limit of 0.01 wt% is reached with an enrichment of free
      fibres of chrysotile in the sample using a standard laboratory elutriator for
      sedimentation analysis. The chrysotile quantitative determination is performed
      both by X-ray powder diffraction, using the internal standard and reference
      intensity ratio methods, and by Fourier-transform infrared absorption
      spectroscopy. The procedure can be successfully applied to different soils after
      removal, by a thermal treatment, of the matrix components which can interfere.
      This straightforward method fulfils the request of public institutions and
      private companies for an appropriate quantitative determination of chrysotile
      free fibres in contaminated soils.

PMID- 12802569
TI  - Pressurized wet digestion in open vessels.
AB  - The High Pressure Asher (HPA-S) was adapted with a Teflon liner for pressurized
      wet digestion in open vessels. The autoclave was partly filled with water
      containing 5% (vol/vol) hydrogen peroxide. The digestion vessels dipped partly
      into the water or were arranged on top of the water by means of a special rack
      made of titanium or PTFE-coated stainless steel. The HPA-S was closed and
      pressurized with nitrogen up to 100 bars. The maximum digestion temperature was
      250 degrees C for PFA vessels and 270 degrees C for quartz vessels. Digestion
      vessels made of quartz or PFA-Teflon with volumes between 1.5 mL (auto sampler
      cups) and 50 mL were tested. The maximum sample amount for quartz vessels was 0.5
      1.5 g and for PFA vessels 0.2-0.5 g, depending on the material. Higher sample
      intake may lead to fast reactions with losses of digestion solution. The samples
      were digested with 5 mL HNO(3) or with 2 mL HNO(3)+6 mL H(2)O+2 mL H(2)O(2). The
      total digestion time was 90-120 min and 30 min for cooling down to room
      temperature. Auto sampler cups made of PFA were used as digestion vessels for
      GFAAS. Sample material (50 mg) was digested with 0.2 mL HNO(3)+0.5 mL H(2)O+0.2
      mL H(2)O(2). The analytical data of nine certified reference materials are also
      within the confidential intervals for volatile elements like mercury, selenium
      and arsenic. No cross contamination between the digestion vessels could be
      observed. Due to the high gas pressure, the diffusion rate of volatile species is
      low and losses of elements by volatilisation could be observed only with diluted
      nitric acid and vessels with large cross section. In addition, cocoa, walnuts,
      nicotinic acid, pumpkin seeds, lubrication oil, straw, polyethylene and coal were
      digested and the TOC values measured. The residual carbon content came to 0.2-10%
      depending on the sample matrix and amount.

PMID- 12802570
TI  - Determination of hydroxyl radical by capillary electrophoresis and studies on
      hydroxyl radical scavenging activities of Chinese herbs.
AB  - High-performance capillary electrophoresis (CE) with electrochemical detection
      (ED) was employed to determine hydroxyl radicals in the Fenton reaction. Hydroxyl
      radicals can react with salicylic acid to produce 2,3-dihydroxy benzoic acid and
      2,5-dihydroxy benzoic acid, which can be analyzed by CE-ED. Based on this
      principle, hydroxyl radicals were determined indirectly. In a 20 mmol/L phosphate
      running buffer (pH 7.4), 2,3-dihydroxy benzoic acid and 2,5-dihydroxy benzoic
      acid would elute simultaneously from the capillary within 6 min. As the working
      electrode, a 300 microm diameter carbon-disk electrode exhibits good responses at
      +0.60 V (vs. SCE) for the two analytes. Peak currents of the two analytes are
      additive. Excellent linearity was obtained in the concentration range from
      1.0x10(-3) mol/L to 5.0x10(-6) mol/L for 2,3-dihydroxy benzoic acid. The
      detection limit (S/N=3) was 2.0x10(-6) mol/L. This method was successfully
      applied for studying hydroxyl radical scavenging activities of Chinese herbs. It
      is testified that Apocynum Venetum L., Jinkgo bibola L., Morus alba L. and
      Rhododendron dauricum L. have strong hydroxyl radical scavenging activities.

PMID- 12802571
TI  - Preconcentration using diethylenetriaminetetraacetic acid-functionalized
      polysiloxane (DETAP) for determination of molybdenum(VI) in seawater by ICP-OES.
AB  - This paper reports a new method for preconcentration and separation of trace
      amounts of molybdenum in seawater samples prior to determination by inductively
      coupled plasma-atomic emission spectroscopy (ICP-OES).
      Diethylenetriaminetetraacetic acid-functionalized polysiloxane (DETAP) was
      synthesized by carboxymethylation of amino groups on triamine immobilized
      polymer, which was prepared by modification of 3-chloropropylpolysiloxane with
      diethylenetriamine. The resulting polysiloxane is highly selective and efficient
      in chelating Mo(VI) at trace levels. It can be used as a column packing material.
      The polysiloxane column can be reused over ten times without losing its original
      properties, so it is suitable for preconcentration of molybdenum species in
      seawater samples before determination. The parameters governing the
      characteristics of polysiloxane for adsorption of Mo(VI) were investigated. These
      include the effect of pH, amount of polysiloxane, equilibrium time, adsorption
      isotherm, maximum adsorption capacity, interfering ions, flow rate, capacity for
      reuse, and desorption. The precision of the preconcentration method, calculated
      as the relative standard deviation of seawater samples, was 3%. The
      preconcentration factor was 100. The detection limit, defined as 3 times the
      standard deviation of five replicate measurements of the blank sample at pH 3,
      was 0.17 microg L(-1). Measurement results for standard reference materials were
      in good agreement with the certified values [(CRMs), NASS-2 Seawater (Open Ocean)
      and CASS-2 Seawater (Coastal)].

PMID- 12802572
TI  - Determination of mercury in SRM crude oils and refined products by isotope
      dilution cold vapor ICP-MS using closed-system combustion.
AB  - Mercury was determined by isotope dilution cold-vapor inductively coupled plasma
      mass spectrometry (ID-CV-ICP-MS) in four different liquid petroleum SRMs. Samples
      of approximately 0.3 g were spiked with stable (201)Hg and wet ashed in a closed
      system (Carius tube) using 6 g of high-purity nitric acid. Three different types
      of commercial oils were measured: two Texas crude oils, SRM 2721 (41.7+/-5.7 pg
      g(-1)) and SRM 2722 (129+/-13 pg g(-1)), a low-sulfur diesel fuel, SRM 2724b
      (34+/-26 pg g(-1)), and a low-sulfur residual fuel oil, SRM 1619b (3.5+/-0.74 ng
      g(-1)) (mean value and 95% CI). The Hg values for the crude oils and the diesel
      fuel are the lowest values ever reported for these matrices. The method detection
      limit, which is ultimately limited by method blank uncertainty, is approximately
      10 pg g(-1) for a 0.3 g sample. Accurate Hg measurements in petroleum products
      are needed to assess the contribution to the global Hg cycle and may be needed in
      the near future to comply with reporting regulations for toxic elements.

PMID- 12802573
TI  - Measurement of the perfection of nanoscale multilayers.
AB  - In modern materials science the characterisation of nanostructures is becoming
      increasingly important. For measurement of the quality of nanoscale multilayer
      arrangement with high spatial resolution a method is described that is based on
      the broadening of the spots in the Fourier transformation of transmission
      electron microscopic images of multilayer cross-sections. Using this method on
      Si/Ge superlattices with periodic lengths between 4 and 12 nm it could be
      quantitatively shown that the layer perfection decreases with increasing periodic
      length. The transition from elastic to plastic deformation between the Si and Ge
      layers at larger periodic lengths can be the reason for this behaviour.

PMID- 12802574
TI  - Optical sensor for carbon dioxide combining colorimetric change of a pH indicator
      and a reference luminescent dye.
AB  - A new optical CO(2) sensor based on the luminescence intensity change of the
      europium(III) complex tris(thenoyltrifluoroacetonato) europium(III) dihydrate
      ([Eu(tta)(3)]) caused by the absorption change of various pH indicators-thymol
      blue, phenol red, or cresol red-with CO(2) was developed and its CO(2) sensing
      properties were investigated. For all the CO(2) sensors using pH indicators the
      observed luminescence intensity from [Eu(tta)(3)] at 613 nm increased with
      increasing CO(2) concentration. The linear calibration method based on the plot
      of (I(100)-I(0))/(I-I(0)) versus the inverse of CO(2) concentration was
      suggested, where I(0) and I(100) were luminescence intensities at 613 nm of the
      CO(2) sensor film in 100% nitrogen and 100% gaseous CO(2). In all cases the plots
      showed good linearity and the correlation factors of the plots, r(2), were 0.991
      for thymol blue, 0.990 for phenol red, and 0.998 for cresol red. The slopes of
      the plots (A/B) for thymol blue, phenol red, and cresol red were 2.2, 5.2, and
      9.0%, respectively. The response times of the CO(2) sensor film were 4.0 s for
      thymol blue, 4.4 s for phenol red, and 8.8 s for cresol red for switching from
      nitrogen to CO(2), and the recovery times of films were 36 s for thymol blue,
      39.2 s for phenol red, and 56.6 s for cresol red for switching from CO(2) to
      nitrogen. The signal changes were fully reversible and hysteresis was not
      observed during the measurements. The highly sensitive CO(2) sensor was developed
      using thymol blue as an indicator for the CO(2)-sensing probe.

PMID- 12802575
TI  - A thorough study of the surface wax of apple fruits.
AB  - The composition of the surface waxes of three apple ( Malus domesticaL.)
      cultivars ("Florina", "Golden B" and "Ozark Gold") has been studied by means of
      spectroscopic and GC-MS analysis of the class-fractionated mixture of components.
      Odd n-alkanes, mainly C(27) and C(29) molecules, are prevalent in the saturated
      fraction. Small concentrations of alkenes were also found; the C(28:1) component
      is strongly (72%) in excess over the other 1-alkenes. Straight-chain esters
      (mainly of palmitic acid) of saturated primary alcohols (C(18)-C(30)) were also
      detected; whereas the acyl moiety is made up essentially of an even number of
      carbons, the alcohol counterpart does not exhibit this characteristic. Aldehydes
      are present (C(20)-C(30)) with the homologue patterns C(26)-C(30) most strongly
      represented. Straight-chain free secondary alcohols characterize the waxes of
      "Florina" and "Ozark Gold"; the hydroxy function is located far from the
      extremity of the carbon framework. Outstanding is the presence of three alcohols
      with 29 carbon centres. These alcohols are accompanied by free straight-chain
      primary alcohols, mainly with even-numbered carbon chains in the range C(26)
      C(30). Free fatty acids are present; all of have a framework of even-numbered
      carbon chains mainly in the range C(16)-C(20). C(18:1) (oleic acid) is well
      represented.

PMID- 12802576
TI  - A toxicity view of the pesticide picloram when immobilized onto a silica gel
      surface.
AB  - The pesticide picloram (4-amino-3,5,6-trichloropicolinic acid) was anchored onto
      silica gel to yield a new surface. Isothermal microcalorimetry was applied to
      study the toxic effects caused to microbial activity of a typical Brazilian
      agricultural soil by application of free and immobilized picloram. The activity
      of the microorganisms in 1.50 g of soil sample was stimulated by addition of 6.0
      mg of glucose plus 6.0 mg of ammonium sulfate under 34.8% controlled humidity at
      298.15+/-0.02 K. The activity was recorded through power-time curves for
      increasing amounts of the active principle, varying from zero to 10.00 microg g(
      1). The increasing amounts of picloram, either free or immobilized, caused a
      decrease of the original thermal effect. The calorimetric data showed that the
      anchored pesticide presented a much lower toxic effect than the free picloram on
      the microbial activity.

PMID- 12802577
TI  - Nanostructure evolution studies of bulk polymer materials with synchrotron
      radiation: progress in method development.
AB  - The prospects of a modern analysis of nanostructure evolution during the
      processing of polymer materials by means of scattering from synchrotron radiation
      are demonstrated in examples. The beam sources have gained stability, shortages
      are located in beamline setups and in method development for the quantitative
      analysis of voluminous data sets. By using the proposed multidimensional chord
      distribution function (CDF) analysis method, nanostructure information from small
      angle X-ray scattering (SAXS) data are extracted and visualised. The method can
      be automated if the beamline setup is able to deliver a full data set with simple
      constraints. In this case even a simultaneous data evaluation is possible (while
      one pattern is accumulated, the previous one is analysed). The advantages of the
      method are demonstrated in a study of the straining of a thermoplastic elastomer.
      The possibilities of an automated analysis are demonstrated in an investigation
      of the crystallisation behaviour of high-pressure injection-moulded polyethylene
      (HPIM-PE). The achievable results of nanostructure analysis of polymer materials
      are discussed. It is shown that the time-resolved SAXS of polymer materials
      studied during a transformation and analysed by the CDF method is not just a
      powerful tool to investigate the relationship between structure and properties of
      materials; the information that can be gained concerning the processes that
      control nanostructure evolution is equally important. In the future the
      enlightenment of such relationships may help to tailor polymer materials with
      respect to their properties and, beyond that, to improve assessments concerning
      their aging.

PMID- 12802578
TI  - Relation between choice of ethanol concentration and response rates under
      progressive- and fixed-ratio schedules: studies with rhesus monkeys.
AB  - RATIONALE: A fundamental problem in the study of drugs as reinforcers is the
      evaluation of a drug's relative reinforcing effects and changes in such effects.
      Relative reinforcing effects can be measured by determining the preference for
      one drug dose relative to another drug dose. However, in IV drug self
      administration studies technical limitations make direct comparisons between drug
      doses difficult. An alternative procedure is to measure the relative persistence
      of behavior across increases in schedule size. OBJECTIVE: To develop a more rapid
      method to measure the relative persistence of behavior. Instead of increasing the
      schedule size across sessions, schedule size was increased within sessions by use
      of a progressive-ratio schedule (PR). METHODS: Male rhesus monkeys orally self
      administered ethanol during daily 3-h sessions. At each concentration responding
      was measured with fixed-ratio (FR) 8 schedules to obtain baseline values.
      Subsequently behavior was studied with a PR schedule. Relative persistence of
      behavior was calculated by dividing the mean response rate under the PR schedule
      by the mean response rate under the FR8 schedules. To compare these findings with
      results of choice between concentrations, monkeys were given concurrent access to
      pairs of ethanol concentrations. RESULTS: The relative persistence of behavior
      increased with increases in drug concentration. When two concentrations were
      concurrently available, the higher concentration maintained higher response
      rates. CONCLUSIONS: The relative persistence of behavior can be efficiently
      measured by dividing the response rate under the PR schedule by the response rate
      under the FR schedule. Measures of relative persistence corresponded well with
      measures of choice and show that relative reinforcing effects increase as dose
      increases.

PMID- 12802579
TI  - In vitro relaxation of vascular smooth muscle by atropine: involvement of K+
      channels and endothelium.
AB  - Cumulative addition of atropine to the organ bath containing endothelium-intact
      (+E) rat aorta, which was precontracted with phenylephrine (PE, 1 microM) and
      subsequently relaxed with carbachol (1 microM), caused biphasic changes in the
      vascular contractility of +E rat aortic rings. Low concentrations of atropine (10
      nM-1.0 microM) caused progressive restoration of contraction to PE; whereas at
      higher concentrations (1-100 microM), atropine caused progressive relaxation.
      Atropine-induced aortic relaxation was significantly inhibited upon endothelium
      removal by either rubbing or saponin treatment, but considerable relaxation still
      persisted in the range of 30-100 microM atropine. Similar findings were also
      obtained when the nitric oxide (NO) generation was inhibited with 300 microM NO
      synthase inhibitor, L-NAME. Atropine-induced relaxation was also observed when 5
      hydroxytryptamine (5-HT) was used as the agonist and the atropine-relaxation was
      more potent at lower concentrations of PE and 5-HT. However, atropine had no
      effect on the contraction elicited by KCl or prostaglandin F(2 alpha). Also,
      atropine-induced relaxation was not affected by indomethacin (1-10 microM),
      nicotine (10-100 microM) or hexamethonium (30 microM). Pretreatment of +E aorta
      with tetraethylammonia (TEA, 3-10 mM) or 4-aminopyridine (4-AP, 1-3 mM) showed
      prominent inhibitory effect on atropine-induced relaxation; on the other hand,
      preincubation with glibenclamide (1-10 microM), BaCl(2) (1-30 microM) or 2 microM
      charybdotoxin and apamin, had little effect on the relaxation induced by
      atropine. When added to tissues after relaxation to atropine, TEA and 4-AP
      concentration-dependently reversed the relaxation in -E aorta, whereas in +E
      aorta, TEA up to 30 mM and 4-AP up to 10 mM only partially affected atropine
      induced relaxation. Although TEA and 4-AP potentiated the PE-contraction, such
      potentiation is unlikely to contribute to the change in sensitivity to atropine
      induced relaxation, since in the presence of 15 mM KCl, which also potentiated PE
      contraction to a comparable extent, the atropine-relaxation remains unchanged.
      Scopolamine also acts like atropine, except that the effect of scopolamine was
      smaller than that of atropine and is primarily endothelium-dependent. Atropine
      induced relaxation also occurs in medium artery (renal artery) and small muscular
      artery (mesenteric artery). In conclusion, atropine-relaxation is mediated in
      part via voltage-dependent K(+) channels in both smooth muscle and endothelium
      and forms the mechanistic basis for the observed vasodilation, reduced blood
      pressure and facial flushing following atropine overdose.

PMID- 12802580
TI  - Effect of cytochrome P-450 inhibition on tetrahydrofuran-induced hepatocellular
      proliferation in female mice.
AB  - The studies presented were designed to investigate the effects of cytochrome P450
      inhibition on tetrahydrofuran-induced hepatocellular proliferation in female
      B6C3F(1) mice. Groups of female B6C3F(1) mice were exposed to dynamic atmospheres
      containing tetrahydrofuran (THF) concentrations of 0, 5,400 or 15,000 mg/m(3) for
      6 h per day, for 5 consecutive days. One-half of the animals in each THF exposure
      group were pretreated with the cytochrome P450 inhibitor 1-aminobenzotriazole
      (ABT) at 100 mg/kg (i.p.) 1 h before the start of each THF exposure period.
      Treatment with THF at 15,000 mg/m(3) caused marked microsomal enzyme induction in
      the liver. The cytochrome P450 content was nearly doubled (+98%),
      pentoxyresorufin-O-depentylase (PROD) and ethoxyresorufin-O-deethylase (EROD)
      activities were increased by 600% and 160%, respectively. ABT pretreatment
      effectively blocked microsomal enzyme induction at 15,000 mg/m(3). THF exposure
      had no effect on the subcellular morphology of hepatocytes, whereas ABT
      pretreatment caused centrilobular fatty change. THF at 15,000 mg/m(3) caused
      increased cell proliferation in zone 3 (central vein region) of the liver
      (according to Rappaport), as indicated by a significantly higher PCNA
      (Proliferating Cell Nuclear Antigen) labelling index, but there were no effects
      at 5,400 ppm. ABT pretreatment prior to THF exposure at 15,000 mg/m(3) caused an
      exacerbated proliferative response of mouse liver, significantly higher PCNA
      labelling indices being observed in zones 2 (midzonal region) and 3. The
      exacerbated proliferative response of mouse liver under conditions of inhibited
      THF metabolism suggests that the mitogenic effects are related to prevailing THF
      tissue concentrations and not to the generation of THF oxidative metabolite(s).

PMID- 12802581
TI  - Tamoxifen: 28-day oral toxicity study in the rat based on the Enhanced OECD Test
      Guideline 407 to detect endocrine effects.
AB  - The main objective of this 28-day oral gavage toxicity study in the rat was to
      investigate which of the current and/or additional parameters of the OECD Test
      Guideline 407 would reliably and sensitively detect the endocrine-mediated
      effects of the nonsteroidal antiestrogen tamoxifen. In addition, as this study
      was performed using two subgroups of five animals of each sex run concurrently,
      it enabled an assessment of the intralaboratory reproducibility while also
      assessing the potential value of using ten animals of each sex per group instead
      of using the standard five animals of each sex per group stipulated by the
      current guideline. Tamoxifen was administered daily by gavage to groups of 7-week
      old Wistar rats for at least 28 days at dose levels of 5, 30, or 200 microg/kg
      body weight. Additional parameters specified in the enhanced OECD Test Guideline
      407 were spermatozoa enumeration and morphology of the cauda epididymis, hormonal
      analysis of the thyroid-stimulating hormone (TSH), triiodothyronine (T3) and
      thyroxine (T4) levels, monitoring of the estrous cycle during week 4 of treatment
      to ensure females were in diestrus on the day of terminal sacrifice, organ weight
      of ovary, uterus, thyroid gland, prostate gland (ventral and dorsolateral parts),
      seminal vesicles with coagulation glands and pituitary gland, and microscopic
      investigation of the pituitary gland, vagina, mammary gland, seminal vesicles
      with coagulating glands, epididymis, and prostate gland (ventral and dorsolateral
      parts). Overall, 200 microg/kg per day was considered to be the Maximum Tolerated
      Dose (MTD) in both sexes, resulting in a marked reduction of body weight gain,
      together with slight effects on clinical signs, hematology, plasma chemistry, and
      microscopic changes in some endocrine tissues. Five micrograms per kilogram per
      day represented the No Observed Adverse Effect Level (NOAEL) in males and the No
      Observed Effect Level (NOEL) in females. At the intermediate dose level (30
      microg/kg per day), the current OECD Test Guideline 407 was appropriate to detect
      the specific endocrine-related changes induced by tamoxifen in females, based on
      the histopathology findings observed in the ovary and the uterus. The additional
      parameters which were found to be changed in females (thyroid hormone levels,
      ovary and uterus weights, and histopathology of vagina) provided supplementary
      information further confirming tamoxifen-mediated endocrine effects. In males,
      when data from the current Test Guideline 407 were considered at the intermediate
      dose level, specific endocrine effects were only indicated on the basis of the
      histopathology findings observed in the prostate gland. The additional parameters
      examined which were found to be changed (prostate gland and seminal vesicle
      weights, and histopathology of seminal vesicle and mammary gland) were necessary
      to confirm the specific tamoxifen-mediated endocrine effects. Hence, amongst the
      additional parameters contained in the enhanced OECD Test Guideline 407, organ
      weights and histopathological examination of endocrine-related organs were the
      most helpful in confirming the detection of tamoxifen-mediated endocrine effects.
      The reproducibility evaluation showed that a group size of five animals of each
      sex consistently allowed the detection of endocrine effects with the current Test
      Guideline in both sexes at the high dose level and in females at the intermediate
      dose level. Doubling the animal number from five to ten of each sex per dose
      level did not notably increase the sensitivity of detection of endocrine-mediated
      effects.

PMID- 12802582
TI  - Autoimmune subepidermal bullous skin diseases: the impact of recent findings for
      the dermatopathologist.
AB  - In recent years improved knowledge of the mechanisms of intercellular and cell
      matrix adhesion has led to better understanding of the blistering process in many
      bullous dermatoses. The wide characterisation of adhesion molecules has partially
      changed some traditional views and invariably has made the routine work of the
      pathologist more complex. If understanding cell-cell cohesion structures such as
      desmosomes and adherens junctions is complex enough, the cell-matrix adhesion
      structures, such as hemidesmosomes and their structural analogues on the basement
      membrane and superficial dermis, are even more complex. Defects of such
      structures cause the subepidermal bullous diseases in which there has been most
      characterisation of the adhesion molecules and has also led to the discovery of
      new diseases (e.g. p200 pemphigoid). Most of the antigens are also the targets
      for mutations seen in patients with the inherited type of epidermolysis bullosa,
      a group of rare blistering genodermatoses. Another important aspect of bullous
      skin conditions is the more accurate definition of the role of the different
      inflammatory cells involved in triggering, development and maintenance of these
      diseases. Recent studies have outlined the important role of T-cell lymphocytes
      and their cytokines in their pathogenesis. All these studies, based mainly on
      highly sophisticated ultrastructural and molecular biology techniques, have
      updated our knowledge of the pathogenesis of blistering diseases. Nevertheless,
      the diagnostic characterisation of bullous diseases remains sometimes difficult,
      and some pathological features and mechanisms still represent an enigma. Diseases
      such as bullous pemphigoid and cicatricial pemphigoid, or anti-laminin
      cicatricial pemphigoid and acquired bullous epidermolysis share the same
      molecular target but have very different clinical manifestations. Explaining this
      phenomenon, probably linked to different expressions of MHC, is one of the
      challenges for the future.

PMID- 12802583
TI  - Tissue microarray technology: validation in colorectal carcinoma and analysis of
      p53, hMLH1, and hMSH2 immunohistochemical expression.
AB  - Tissue microarray technology enables the analysis of hundreds of specimens by
      arranging numerous 0.6-mm tissue core biopsy specimens into a single paraffin
      block. Validation studies are necessary to evaluate the representativeness of
      small disks taken from the original tissue. We validated the tissue microarray
      technology in colorectal carcinoma by analyzing the immunohistochemical
      expression of proteins involved in the two main pathways of colorectal
      carcinogenesis: p53 protein for loss of heterozygosity tumors, hMLH1 and hMSH2
      proteins for microsatellite instability (MSI) tumors. We compared in 30
      colorectal carcinomas (15 MSI(-) and 15 MSI(+)), 8 microarrays disks, and the
      whole section of the block from which they were derived. Tumoral tissue was
      present in 95.7% of the microarray disks. The analysis of three disks per case
      was comparable to the analysis of the whole section in 99.6% (p53), 98.8%
      (hMLH1), and 99.2% (hMSH2) of cases. In the second part we applied the tissue
      microarray technology to 263 consecutive cases of colorectal carcinoma, sampled
      by three cores. We showed that 48.5% overexpressed p53 and 8.7% lost hMLH1 or
      hMSH2. Tissue microarray technology, validated in colorectal carcinoma, appears
      as a useful research tool for rapid analysis of the clinical interest of
      molecular alterations.

PMID- 12802584
TI  - Involvement of DNase gamma in apoptotic DNA fragmentation in histiocytic
      necrotizing lymphadenitis.
AB  - DNA fragmentation induced by endonucleases is a hallmark of apoptotic process.
      One of the endonucleases responsible for apoptotic DNA fragmentation has been
      identified as DNase gamma. It has been suggested that massive nuclear debris
      observed in histiocytic necrotizing lymphadenitis (HNL, Kikuchi disease) results
      mainly from apoptosis of T-lymphocytes rather than necrosis. To identify the role
      of DNase gamma in apoptotic foci of HNL paraffin embedded tissue sections of HNL
      and lymphadenopathy with hyperplastic germinal centers and paracortex in the neck
      lymph nodes were immunohistochemically stained for DNase gamma and the results
      compared with the reactivity of TdT-mediated dUTP nick end labeling (TUNEL).
      Immunoreactivity for DNase gamma was detected in fragmented and condensed nuclei
      found abundantly in HNL as well as TUNEL reactivity. Moreover, the ratio of DNase
      gamma immunoreactivity to TUNEL reactivity, which represents probability of
      apoptosis relevant to DNase gamma, was higher in foci of nuclear debris in HNL
      than in the hyperplastic paracortex in lymphadenopathy including T-cell
      apoptosis. Our findings suggest that apoptosis detected in HNL depends more
      specifically upon DNase gamma than apoptosis in the hyperplastic paracortex of
      lymphadenopathy, and that the dysregulation of DNase gamma activation is involved
      in apoptosis in HNL.

PMID- 12802585
TI  - Amyloid in surgical pathology.
AB  - Amyloid is defined as a proteinaceous tissue deposit that shows a typical green
      birefringence in polarized light after staining with Congo red, the presence of
      non-branching linear fibrils of indefinite length with a mean diameter of 10 nm,
      and a distinct X-ray diffraction pattern consistent with Pauling's model of a
      cross beta-fibril. Amyloid may deposit locally or may present as a systemic
      disease. The origin of amyloid is diverse: 25 different fibril proteins have been
      described so far. The precursor proteins differ from each other in their primary
      structures and functions. The only common denominator is the propensity to form
      anti-parallel cross beta-fibrils under certain circumstances. Early diagnosis of
      amyloid is still a major challenge in surgical pathology. Histological proof can
      be obtained using Congo-red staining and polarization microscopy. However, small
      deposits may be difficult to discern, and sensitivity can be improved using
      fluorescence microscopy. Classification of amyloid is mandatory, since amyloid is
      treatable and different treatment regimens are applied to different amyloid
      diseases. This review focuses on the epidemiology, clinical features, pathology
      and diagnosis of amyloid in surgical pathology.

PMID- 12802586
TI  - Analysis of chromosomal copy number changes and oncoprotein expression in primary
      central nervous system lymphomas: frequent loss of chromosome arm 6q.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare disease. A small number
      of cytogenetic studies of PCNSL have been conducted and several reports have been
      published on associated molecular and protein expression data. We combined these
      approaches in a series of eight PCNSL cases, analyzing the chromosomal
      abnormalities using comparative genomic hybridization (CGH), testing for Epstein
      Barr virus (EBV) involvement by in situ hybridization for EBER, assessing
      expression of p53, Bcl-2, Bcl-6 and CD10 by means of immunohistochemistry, and
      screening for mutations of the TP53 gene by DGGE. TP53 gene mutations and EBV
      expression were not detected. Most of the cases showed p53, Bcl-6 and Bcl-2
      protein expression. CGH revealed DNA copy number changes in all eight cases. The
      most frequent changes were gains of chromosome 12 (63%), chromosome 18 (50%) and
      20q (38%), and loss of chromosome arm 6q (75%). No correlation between protein
      expression and chromosomal abnormalities was found in these eight cases. Although
      gains of chromosome 12, 18 and 20q and loss of 6q have also been reported in
      systemic diffuse large B-cell lymphomas, the frequency of 6q deletion is clearly
      higher in PCNSL. This creates a similarity to primary lymphomas of the testes
      that also frequently have deletions of 6q. This suggests that suppressor genes
      located on chromosome 6q may play a role in the development of lymphomas at
      immunoprivileged sites, like the CNS.

PMID- 12802587
TI  - Developmental expression of XEEL, a novel molecule of the Xenopus oocyte cortical
      granule lectin family.
AB  - We have isolated cDNA clones from a Xenopus laevis embryo library that encode a
      predicted translation product of 342 amino acids containing a signal sequence for
      secretion. The predicted protein has 62-70% amino acid identity with the Xenopus
      oocyte cortical granule lectin (XCGL), the mouse intelectin, the human HL
      1/intelectin and HL-2. Onset of gene expression occurs by gastrulation, and the
      transcripts localize in non-ciliated epidermal cells all over the tailbud
      embryos. The results suggest that the molecule, designated XEEL ( Xenopus
      embryonic epidermal lectin), is a novel XCGL family molecule secreted from the
      embryonic epidermis.

PMID- 12802588
TI  - Expression of FoxE and FoxQ genes in the endostyle of Ciona intestinalis.
AB  - We have analyzed the expression patterns of two Fox genes, FoxE and FoxQ, in the
      ascidian Ciona intestinalis. Expression of Ci-FoxE was specific to the endostyle
      of adults, being prominent in the thyroid-equivalent region of zone 7. Ci-FoxQ
      was expressed in several endodermal organs of adult ascidians, such as the
      endostyle, branchial sac and esophagus. In the endostyle, the pattern of Ci-FoxQ
      expression was similar to that of CiTTF-1, being prominent in the thyroid
      equivalent regions of zones 7 and 8. Therefore, these Fox genes may perform
      thyroid-equivalent functions in the ascidian endostyle.

PMID- 12802590
TI  - Skin-conditioning products in occupational dermatology.
AB  - Moisturizers are frequently used in the prevention of occupational contact
      dermatitis. This review discusses their chemistry and mode of action. Methods to
      prove their preventive efficacy are presented. In addition to pharmacological
      efficacy, subjective factors that influence application of the products and
      compliance come into play. In conclusion, moisturizers are only one element of
      skin-disease prevention at the workplace that should be viewed as a complex,
      inter-dependent system. The efficacy of the complete, integrated system of
      occupational skin care has to be proven.

PMID- 12802591
TI  - No influence of short-term exposure to 50-Hz magnetic fields on cognitive
      performance function in human.
AB  - OBJECTIVES: To examine whether 50-Hz magnetic fields acutely influence cognitive
      performance function in humans. METHODS: The exposure experiment was conducted in
      a wooden room with three-axis coils. Twenty young subjects were exposed to
      circularly polarized 50-Hz/20-mu T magnetic fields for 55 min, during which they
      were requested to perform four cognitive performance tests for evaluation of
      simple reaction time, time and accuracy of choice reaction, time perception, and
      figure perception. RESULTS: No subject detected the existence of the field.
      Statistical analysis revealed no significant influence of the exposure on the
      results of the tests. CONCLUSIONS: The results indicate that extremely low
      frequency electromagnetic fields in the occupational environment are unlikely to
      interfere with human brain function so much as to lower working efficiency or
      accuracy.

PMID- 12802592
TI  - Intermittent extremely low frequency electromagnetic fields cause DNA damage in a
      dose-dependent way.
AB  - OBJECTIVES: Epidemiological studies have reported an association between exposure
      to extremely low frequency electromagnetic fields (ELF-EMFs) and increased risk
      of cancerous diseases, albeit without dose-effect relationships. The validity of
      such findings can be corroborated only by demonstration of dose-dependent DNA
      damaging effects of ELF-EMFs in cells of human origin in vitro. METHODS: Cultured
      human diploid fibroblasts were exposed to intermittent ELF electromagnetic
      fields. DNA damage was determined by alkaline and neutral comet assay. RESULTS:
      ELF-EMF exposure (50 Hz, sinusoidal, 1-24 h, 20-1,000 mu T, 5 min on/10 min off)
      induced dose-dependent and time-dependent DNA single-strand and double-strand
      breaks. Effects occurred at a magnetic flux density as low as 35 mu T, being well
      below proposed International Commission of Non-Ionising Radiation Protection
      (ICNIRP) guidelines. After termination of exposure the induced comet tail factors
      returned to normal within 9 h. CONCLUSION: The induced DNA damage is not based on
      thermal effects and arouses concern about environmental threshold limit values
      for ELF exposure.

PMID- 12802593
TI  - Immunohistochemical study of caspase-3-expressing cells within the pancreas of
      non-obese diabetic mice during cyclophosphamide-accelerated diabetes.
AB  - During insulin-dependent diabetes mellitus, immune cells infiltrate pancreatic
      islets progressively and mediate beta cell destruction over a prolonged
      asymptomatic prediabetic period. Apoptosis may be a major mechanism of beta cell
      loss during the disease. This process involves a proteolytic cascade in which
      upstream procaspases are activated which themselves activate downstream caspases,
      including caspase-3, a key enzyme involved in the terminal apoptotic cascade.
      Here dual-label immunohistochemistry was employed to examine the intra-islet
      expression, distribution and cellular sources of active caspase-3 in the non
      obese diabetic (NOD) mouse given cyclophosphamide to accelerate diabetes. NOD
      mice were treated at day 95 and caspase-3 expression was studied at days 0, 4, 7,
      11 and 14. Its expression was also correlated with advancing disease and compared
      with age-matched NOD mice treated with diluent alone. At day 0 (=day 95), caspase
      3 immunolabelling was observed in several peri-islet and intra-islet macrophages,
      but not in CD4 and CD8 cells and only extremely rarely in beta cells. At day 4,
      only a few beta cells weakly expressed the enzyme, in the absence of significant
      insulitis. At day 7, caspase-3 expression was observed in a small proportion of
      intra-islet macrophages. At day 11, there was a marked increase in the number of
      intra-islet macrophages positive for caspase-3 while only a few CD4 cells
      expressed the enzyme. At day 14, caspase-3 labelling became prominent in a
      significant proportion of macrophages. Only a few CD4 and CD8 cells expressed the
      enzyme. Capase-3 labelling was also present in a proportion of macrophages in
      perivascular and exocrine regions. Surprisingly, beta cell labelling of caspase-3
      at days 11 and 14 was rare. At this stage of heightened beta cell loss, a
      proportion of intra-islet interleukin-1beta-positive cells coexpressed the
      enzyme. Caspase-3 was also observed in numerous Fas-positive cells in heavily
      infiltrated islets. During this late stage, only a proportion of caspase-3
      positive cells contained apoptotic nuclei, as judged by terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labelling (TUNEL). We conclude that during
      cyclophosphamide-accelerated diabetes in the NOD mouse, the predominant
      immunolabelling of caspase-3 in intra-islet macrophages suggests that apoptosis
      of macrophages may be an important mechanism for its elimination. The virtual
      absence of caspase-3 immunolabelling in most beta cells even during heightened
      beta cell loss supports their rapid clearance following their death during
      insulin-dependent diabetes mellitus.

PMID- 12802594
TI  - Localization of brain-type fatty acid-binding protein in Kupffer cells of mice
      and its transient decrease in response to lipopolysaccharide.
AB  - Brain-type fatty acid-binding protein (B-FABP) was localized in Kupffer cells of
      liver of postnatal day 10 (P10) and older mice in immunolight and electron
      microscopy as well as by in situ hybridization histochemistry. The immunoreaction
      products were localized in the cytoplasmic matrix but not within the nucleus.
      After peritoneal injection of lipopolysaccharide (LPS), the immunoreaction for B
      FABP decreased markedly in Kupffer cells at 1 h postinjection and thereafter
      gradually recovered to the preinjection level by 24 h postinjection, although no
      decrease in the mRNA expression was detected in Northern blotting throughout the
      course after the injection. The specific localization of B-FABP, but not the
      other FABPs, in Kupffer cells, and its rapid decrease after LPS injection suggest
      the intimate involvement of B-FABP in Kupffer cells in the inflammatory reaction,
      probably through mediation of n-3 polyunsaturated fatty acids, which are strong
      binders of B-FABP.

PMID- 12802595
TI  - Perfusion-Perls and -Turnbull methods supplemented by DAB intensification for
      nonheme iron histochemistry: demonstration of the superior sensitivity of the
      methods in the liver, spleen, and stomach of the rat.
AB  - Perfusion-Perls and -Turnbull methods supplemented by the intensification with
      3,3'-diaminobenzidine (+ DAB) enabled stronger and more extensive staining of
      nonheme iron than the Perls + and Turnbull + DAB methods carried out on tissue
      sections fixed with 10% formalin in 0.9% saline or PBS. The section- and
      perfusion-Perls + DAB methods are not specific for the demonstration of nonheme
      ferric iron but also stain nonheme ferrous iron. However, owing to its high
      sensitivity, the perfusion-Perls + DAB method would provide useful information
      about nonheme iron deposition regardless of oxidation states in normal and
      pathological conditions. The perfusion-Turnbull + DAB method is specifically
      demonstrable of nonheme ferrous iron and the results from this method showed
      significant stores of nonheme ferrous iron in the hepatocytes, Kupffer cells,
      splenic macrophages, and gastric parietal cells of the rat. Since nonheme ferrous
      iron is considered to be critically involved in free radical generation, the
      perfusion-Turnbull + DAB method would visualize such populations of cells that
      are at risk from free radical damage.

PMID- 12802596
TI  - Immunohistochemical expressions of mGluR5, P2Y2 receptor, PLC-beta1, and IP3R-I
      and -II in Merkel cells in rat sinus hair follicles.
AB  - We previously found that Merkel cells (MCs) of the rat and monkey show a strong
      immunoreaction of the alpha-subunit of Gq protein. The Galphaq-subunit isoform
      activates isozymes of phospholipase C-beta (PLC-beta), which produces inositol
      (1,4,5)-triphosphate (IP3) which mobilizes intracellular Ca(++) from calcium
      stores via IP3 receptors. Glutamate and adenosine triphosphate (ATP), which are
      candidates for neurotransmitters in Merkel endings, are known to couple to
      Galphaq. Although MCs showed positive immunoreactions of metabotropic glutamate
      receptor 5 (mGluR5) in our preliminary study, these cells were not reactive to
      all antibodies to PLC-beta isozymes. We, therefore, reinvestigated
      immunohistochemical affinities to MCs of antibodies to PLC-beta isozymes and
      mGluRs using frozen sections of rat sinus hair follicles that were briefly
      postfixed in formaldehyde. We also studied the immunohistochemical expressions of
      P2Y receptors for ATP and IP3 receptor subtypes using similar sections. Merkel
      cells showed positive immunoreactions of PLC-beta1 and mGluR5. It was also found
      that MCs show positive immunoreactions of P2Y2, IP3R-I, and IP3R-II receptors.
      These results suggest that the Galphaq isoform in MCs couples to both the P2Y2
      receptor and mGluR5 and regulates the intracellular Ca(++) concentration via the
      PLC-beta-IP3 cascade.

PMID- 12802599
TI  - Structure and vascularization of the acetabular labrum with regard to the
      pathogenesis and healing of labral lesions.
AB  - INTRODUCTION: The aim of this study is to examine the structure and
      vascularization of the acetabular labrum with regard to the pathogenesis and
      healing of labral tears. MATERIALS AND METHODS: The labral tissue was
      characterized immunohistochemically and under light microscopy; the collagen
      fibril texture was demonstrated by scanning electron microscopy after temporary
      staggered maceration of the tissue; and the vascularization of the acetabular
      labrum was studied immunohistochemically using antibodies against laminin.
      RESULTS: The peripheral aspect of the acetabular labrum consists of dense
      connective tissue. The internal layer consists of type II collagen-positive
      fibrocartilage. Scanning electron microscopy revealed three distinct layers in
      the acetabular labrum: (1) the articular surface was covered by a meshwork of
      thin fibrils; (2) beneath the superficial network, there is a layer of lamella
      like collagen fibrils; (3) the majority of the collagen fibrils are oriented in a
      circular manner. Blood vessels enter the labrum from the adjacent joint capsule.
      The distribution of vessels within the labrum is not homogenous. Blood vessels
      can be detected only in the peripheral one-third of the labrum. The internal part
      is avascular. CONCLUSION: The result of this study demonstrates that the
      structure of the acetabular labrum is highly significant for the direction of
      traumatic and dysplastic labral lesions. The biomechanical analysis of the
      structure suggests that the labrum is stressed by compressive load. Therefore,
      excision or removal of the labrum may alter physiological functions such as
      enhancing joint stability and load distribution. The vascular pattern identified
      should encourage surgeons to develop repair strategies of peripheral labral tears
      to maintain its functions in the hip.

PMID- 12802598
TI  - Analysis of radiation-induced DNA double-strand breaks misrepair is not
      compromized by broken DNA in human fibroblasts.
AB  - It has been suggested that the technique for measuring repair fidelity of
      radiation-induced DNA double-strand breaks (DSBs) using Southern blotting and
      hybridization to defined regions of the genome could be compromised by broken or
      poorly-digested DNA. Since misrepair of DNA DSBs is an important aspect of
      radiation-induced chromosome aberrations, mutations, and cell killing, we checked
      for such a supposition in non-transformed human fibroblasts. DSB misrepair was
      assessed in a NotI-cleavable DNA fragment of 3.2 Mbp located on the long arm of
      chromosome 21 and detected by D21S1 probe. We hypothesized that the suggested DNA
      degradation, whether spurious in nature or the results of irradiation-induced
      phenomena such as apoptosis and/or necrosis, should be detectable with or without
      NotI restriction enzyme treatment. When the DNA embedded in agarose plugs was
      separated by electrophoresis without prior NotI restriction, no significant
      difference was observed in the relative amount of migrating DNA between the
      control (no irradiation) and 24 h of repair following 80 Gy irradiation.
      Furthermore, only about 10% of the total signal was located below the 3.2 Mbp
      band. This suggests that the amount of DNA fragmentation due to biological
      (apoptosis or necrosis) or technical processes was negligible. The Tunel assay
      supported these results, as there was little to no apoptosis detectable in these
      fibroblasts up to 24 h after irradiation. We conclude that in primary human
      fibroblasts, the NotI method for measuring radiation-induced misrepair is not
      compromised by DNA degradation.

PMID- 12802600
TI  - Treatment of distal radioulnar joint disorders with a modified Sauve-Kapandji
      procedure: long-term outcome with special attention to the DASH Questionnaire.
AB  - INTRODUCTION: An intact distal radioulnar joint (DRUJ) is essential for normal
      functioning of the upper limb. Osteoarthritis of the DRUJ often leads to ulnar
      wrist pain, limitation of forearm rotation and reduced grip strength, all of
      which limit activities of daily living. Once the joint is damaged, salvage
      procedures are recommended. MATERIALS AND METHODS: Between 1986 and 1996 a
      modified Sauve-Kapandji procedure was performed in 117 patients with painfully
      limited forearm rotation and osteoarthritis of the distal radioulnar joint
      (DRUJ). Of the 117 patients, 73 women and 32 men, whose ages at operation ranged
      from 22 to 74 years (average 58 years), were retrospectively reviewed clinically
      and radiologically 8 years (range 5-12 years) after the operation. The DASH
      questionnaire was used with 53 patients, 43 patients were accepted for the study,
      and 10 were excluded. RESULTS: Forearm rotation improved in all patients, ulnar
      wrist pain was reduced in 97% of the patients, and 9% had mild pain at the
      proximal ulnar stump. Grip strength improved from a preoperative mean of 38% to a
      postoperative mean of 55% compared with the contralateral side. The mean DASH
      score was 28 points (range 0-53 points). In all cases the arthrodesis fused
      within 8 weeks. The radiographs showed approximation between the proximal ulna
      stump and the radius compared with the preoperative situation in 74% of the
      patients. CONCLUSION: Our clinical and radiological findings suggest that the
      Sauve-Kapandji procedure is indicated in symptomatic, non-reconstructable
      disorders of the DRUJ. The DASH questionnaire provides a general view of the
      functional outcome after the Sauve-Kapandji procedure. The DASH questionnaire is
      very helpful in evaluating the effect of the Sauve-Kapandji procedure on the
      entire upper limb.

PMID- 12802597
TI  - Effects of the plasticiser DEHP on lung of newborn rats: catalase
      immunocytochemistry and morphometric analysis.
AB  - Experimental administration of di-(2-ethylexyl)-phthalate (DEHP), a plasticiser
      employed in the fabrication of polyvinyl chloride (PVC), causes increases in
      lipid metabolising enzymes along with marked peroxisomal proliferation. The
      effects are found in several mammalian tissues, of which the rodent liver is the
      most responsive target. Leakage of DEHP from PVC devices is favoured by high
      temperature and contact with lipid-containing biological fluids. Since preterm
      babies are currently ventilated through endotracheal PVC tubes, it seemed
      worthwhile to investigate DEHP effects on immature mammalian lung. In this
      research, female rats were fed with DEHP in the last week of pregnancy and after
      delivery, and lungs were excised from 2-day-old pups. At this age, in fact, rat
      lung histological features closely resemble those found in 24- to 36-week-old
      human fetuses. In treated animals, morphometric analysis of histological
      parameters revealed a dramatic decrease in the number of parenchymal airspaces,
      together with significant increases in their mean size. Moreover, cytochemical
      detection of the peroxisomal marker catalase revealed an increase in the number
      of type II pneumocytes. Our findings closely resemble abnormal histological
      features observed in autoptic lung specimens from children affected with chronic
      lung diseases.

PMID- 12802603
TI  - Synovial sarcoma--unusual presentation with cerebral hemorrhage.
AB  - INTRODUCTION: Soft-tissue sarcomas account for 1% of all malignancies in adults.
      Typical symptoms comprise a growing and painless mass. Occasionally, the
      diagnosis is facilitated by secondaries. MATERIALS AND METHODS: Here we report
      the first case presented with intracranial hemorrhage caused by a metastasis of a
      previously unknown synovial sarcoma. The 74-year-old female patient was under
      anticoagulation for recurrent thrombosis of the right popliteal vein due to
      compression by the sarcoma, misdiagnosed as Baker's cyst. The brain metastasis
      was resected, and after an incisional biopsy of the suspected tumor, which
      confirmed the diagnosis of a synovial sarcoma, an above knee amputation was
      performed because of the invasion of the neurovascular structures in the
      popliteal fossa. RESULTS: The patient died 11 months after the initial event from
      pulmonary and further brain metastases. CONCLUSION: Brain metastases are seldom
      the primary factor in the management of advanced synovial sarcoma. Initially, the
      primary tumor was thought to be a benign cyst; we therefore recommend a
      biopsy/excision of lesions greater than 5 cm in size and with growth tendency to
      allow appropriate treatment.

PMID- 12802604
TI  - A patient with self-inflicted injuries of the cervical vertebrae and spinal cord.
AB  - INTRODUCTION: We encountered a patient with methamphetamine addiction who had
      self-inflicted injuries of the cervical vertebrae and spinal cord. MATERIALS AND
      METHODS: The patient hit his head on the wall many times and showed abnormal
      behavior due to the addiction. Radiograph and CT revealed cervical vertebral
      injuries. Clinical findings indicated that the injuries had affected the spinal
      cord. RESULTS: Conservative treatment was performed because reduction of the
      cervical vertebrae was good.

PMID- 12802605
TI  - 4-repeat tauopathy sharing pathological and biochemical features of corticobasal
      degeneration and progressive supranuclear palsy.
AB  - We report a 67-year-old man with 4-repeat (4R) tauopathy sharing both features of
      corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP).
      Although CBD and PSP have a common pathological feature that 4R tau accumulates
      in neurons and glia, recent pathological studies have confirmed differences
      between the two disorders. Clinical features of the present case were
      asymmetrical apraxia, parkinsonism, memory disturbance, disorientation and left
      limb myoclonus with a 5-year history. Pathological features were the widespread
      occurrence of 4R tau-positive structures including pre-tangles, neurofibrillary
      tangles, astrocytic plaques, tufted astrocytes, coiled bodies and argyrophilic
      threads. Biochemically, immunoblotting of insoluble tau demonstrated the low
      molecular fragments of 37 kDa and 33 kDa observed in typical CBD and PSP,
      respectively, in addition to the presence of 4R tau isoforms. The present case
      shared tau-related pathological and biochemical features of CBD and PSP. These
      findings support that CBD and PSP are closely associated disorders having a
      pathogenesis common to 4R tauopathy.

PMID- 12802606
TI  - A novel aspartate protease gene, ALP56, is related to morphological features of
      colorectal adenomas.
AB  - BACKGROUND AND AIMS: The recently identified aspartate protease gene ALP56 is up
      regulated in human malignant tumors, including colorectal cancers, but the
      relationship remain unclear between ALP56 gene expression and clinicopathological
      findings, as well as when genetic alterations in ALP56 occur during the
      colorectal adenoma-carcinoma sequence. We therefore investigated expression of
      ALP56 mRNA in various human colorectal tissues. MATERIALS AND METHODS: We
      examined 18 colorectal adenomas 22 cancers, and 24 adjacent normal mucosal
      samples from patients undergoing conventional resection or endoscopic mucosal
      resection. Expression of ALP56 mRNA was determined by quantitative reverse
      transcription polymerase chain reaction. RESULTS: Up-regulation of ALP56 gene
      transcription was observed in both adenomas and cancers compared to normal
      mucosa. ALP56 expression in exophytic adenomas was significantly greater than in
      flat adenomas. CONCLUSION: ALP56 may contribute to colorectal adenoma formation
      and to an exophytic growth pattern in these adenomas.

PMID- 12802607
TI  - Adriamycin effects on the chick embryo.
AB  - Adriamycin is an anthracycline, anti-neoplastic drug with known teratogenic
      effects on foetal rats in what is known as the Adriamycin rat model (ARM). This
      includes conditions similar to those in newborn humans, known collectively as the
      VACTERL association. This comprises vertebral (V), anorectal (A), cardiac (C),
      tracheoesophageal (TE), renal (R) and limb (L) anomalies. We designed this study
      to test the hypothesis that the administration of Adriamycin to chick embryos
      would cause similar anomalies to those in the VACTERL association seen in the
      ARM. Fertilized Ross eggs received Adriamycin doses from 2-50 microg into the air
      sac and from 0.9-6 microg into the albumin. Administration varied from day 0-3
      (D(0-3)) with D(0) being the first day of incubation. Control eggs received
      saline. Embryos were incubated at 38 degrees C and a relative humidity of 70%.
      Embryos were recovered on D(14), paraffin-embedded and transverse sections
      studied for morphological abnormalities. In the air sac group ( n=142), 71% of
      Adriamycin embryos survived versus 86% of controls (n=29). In the albumin group
      (n=121), 42% of Adriamycin embryos survived versus 55% of controls (n=69). No
      embryos demonstrated anomalies consistent with the VACTERL association. Ventral
      defects affected 1% of surviving Adriamycin embryos versus 4% of controls in the
      air sac group. In the albumin group, 19.8% of surviving Adriamycin embryos had
      ventral defects compared to 15.7% of surviving controls. Anophthalmia affected 1%
      of the surviving embryos in the Adriamycin air sac group and 2% of the Adriamycin
      albumin group. No controls developed anophthalmia. Exencephaly affected 2% of the
      survivors in the Adriamycin air sac group but none of the albumin group or
      controls. The administration of Adriamycin to chick embryos in comparable doses
      and times to those used in the ARM does not appear to produce comparable effects
      in relation to developmental anomalies, such as the VACTERL association. Despite
      examining different administration routes and mimicking the ARM, by giving
      Adriamycin to embryos at gastrulation, we were unable to re-create the anomalies
      seen in the ARM.

PMID- 12802608
TI  - Pediatric sand aspiration: case report and literature review.
AB  - Sand aspiration is a rare but life-threatening event that occurs in the pediatric
      and adult populations after cave-ins or near drownings. We report the case of a
      10-year-old boy who suffered from aspiration of particulate matter after being
      buried in sand. In addition, we performed a literature review regarding similar
      cases and their treatment of aspiration of significant amounts of particulate
      matter. Treatment of the victims ranges from conservative to very aggressive. The
      treatment employed is dictated by the patient's current condition and the
      services available to the physician.

PMID- 12802609
TI  - Identification of brain malformations: neuropathological approach.
AB  - INTRODUCTION: The sophistication of prenatal brain imaging (US, MRI) has awakened
      interest in fetal neuropathology and changed the concept of brain malformations,
      defined until recently through descriptive terms and considered as senseless
      accidents of development. Usually, most CNS malformations are documented from a
      clinical and radiological point of view. However, only a detailed
      neuropathological study permits their exact phenotype to be established, which is
      instrumental for a precise diagnosis and cause analysis. DISCUSSION: After
      pregnancy termination for fetal malformations (or prenatal death) full autopsy
      and frozen tissue storage for DNA analysis are mandatory. The delay between death
      and autopsy should be limited because of the rapid autolysis of brain tissue.
      Detailed neuropathological and cause analysis have made it clear that each brain
      malformation is phenotypically "unique" and causally heterogeneous. Molecular
      studies have shown that mutations in different genes involved in a signaling
      pathway may result in a similar malformation. In addition, signaling pathways may
      be a possible target of toxic agents, which will mimic the genetic causes of
      malformations. These findings have raised growing interest in the early
      patterning of the developing nervous system in humans and its molecular
      controlling pathways. Consequently, brain malformations are now evaluated with
      special regard to their mechanism and cause analysis, considering fetal,
      maternal, and placental pathology. The predictive value of this multidisciplinary
      approach is now well demonstrated and has led, in some conditions, to gene
      identification, which is crucial for genetic counseling. It permits a prenatal
      molecular diagnosis as early as the 10-12th gestational week on chorionic villus
      sampling.

PMID- 12802610
TI  - Uptake and metabolism of pyrrolizidine alkaloids in Longitarsus flea beetles
      (Coleoptera: Chrysomelidae) adapted and non-adapted to alkaloid-containing host
      plants.
AB  - Several Longitarsus flea beetle species sequester pyrrolizidine alkaloids
      acquired from their Asteraceae and Boraginaceae host plants. We carried out
      feeding and injection experiments using radioactively labeled pyrrolizidine
      alkaloids to investigate the physiological mechanisms of uptake, metabolism and
      storage of alkaloids in adult beetles. We examined six Longitarsus species
      belonging to different phylogenetic clades in a comparative approach. All species
      that accepted pyrrolizidine alkaloids in a preceding food choice study showed the
      ability both to store pyrrolizidine alkaloid N-oxides and to metabolize tertiary
      pyrrolizidine alkaloids into their N-oxides. Regardless of whether the beetles'
      natural host plants contain pyrrolizidine alkaloids or not, these species were
      found to possess an oxidizing enzyme. This oxygenase appears to be specific to
      pyrrolizidine alkaloids: [3H]Atropine and [14C]nicotine, two alkaloids not
      related to pyrrolizidine alkaloids, were neither stored nor N-oxidized by any of
      the tested species. One species, L. australis, that strictly avoids pyrrolizidine
      alkaloids behaviorally, exhibited a lack of adaptations to pyrrolizidine
      alkaloids on a physiological level as well. After injection of tertiary
      [14C]senecionine, beetles of this species neither N-oxidized nor stored the
      compounds, in contrast to L. jacobaeae, an adapted species that underwent the
      same treatment. L. jacobaeae demonstrated the same efficiency in N-oxidation and
      storage when fed or injected with tertiary [14C]senecionine.

PMID- 12802611
TI  - The correlation of preoperative CT, MR imaging, and clinical staging (FIGO) with
      histopathology findings in primary cervical carcinoma.
AB  - The aim of this study was to compare the preoperative findings of
      abdominal/pelvic CT and MRI with the preoperative clinical International
      Federation of Obstetrics and Gynecology (FIGO) staging and postoperative
      pathology report in patients with primary cancer of the cervix. Thirty-six
      patients with surgical-pathological proven primary cancer of the cervix were
      retrospectively studied for preoperative staging by clinical examination, CT, and
      MR imaging. Studied parameters for preoperative staging were the presence of
      tumor, tumor extension into the parametrial tissue, pelvic wall, adjacent organs,
      and lymph nodes. The CT was performed in 32 patients and MRI (T1- and T2-weighted
      images) in 29 patients. The CT and MR staging were based on the FIGO staging
      system. Results were compared with histological findings. The group is consisted
      of stage 0 (in situ):1, Ia:1, Ib:8, IIa:2, IIb:12, IIIa:4, IVa:6, and IVb:2
      patients. The overall accuracy of staging for clinical examination, CT, and MRI
      was 47, 53, and 86%, respectively. The MRI incorrectly staged 2 patients and did
      not visualize only two tumors; one was an in situ (stage-0) and one stage-Ia
      (microscopic) disease. The MRI is more accurate than CT and they are both
      superior to clinical examination in evaluating the locoregional extension and
      preoperative staging of primary cancer of the cervix.

PMID- 12802612
TI  - Imaging diagnosis of perforated jejunal diverticulitis.

PMID- 12802614
TI  - Mn-DPDP-enhanced 24-h delayed-scan MRI of hepatocellular carcinoma is correlated
      with histology.

PMID- 12802615
TI  - Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing
      activatable macromolecular optical probe.
AB  - The aim of this study was to validate the use of near infrared fluorescence
      imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An
      optical contrast probe that is activated by cystein proteases, such as cathepsin
      B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to
      quantitate the uptake of the optical probe in lymphatic tissue, the
      biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen
      Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.)
      with the NIRF-probe (2 micromol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and
      imaged 24 h after injection. Signal intensities and target-to-background ratios
      of various lymph nodes were measured by manual regions of interest (ROIs).
      Additional signal intensity measurements were performed of excised lymph nodes
      (n=21) from i.v. injected mice (24 h after injection) and compared with excised
      lymph nodes (n=8) of non-injected mice. The probe employed in this study was
      lymphotropic with approximately 3-4% accumulation in lymph nodes (3.4+/-0.8%
      ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a
      significant increase in lymph node fluorescence signal from baseline 26+/-7.6
      arbitary units (AU) to 146+/-10.9 AU (p<0.0001). A significant increase in lymph
      node fluorescence signal was also seen in vivo throughout the body after i.v.
      injection (96+/-7.8 AU) and/or regionally after s.c. injection (141+/-11.5 AU) in
      comparison with baseline autofluorescence (26+/-7.6 AU). Target-to-background
      ratio was significantly higher after s.c. injection (6.6%+/-0.81) compared with
      i.v. injection (4.8+/-0.67%). Detection and visualization of lymph nodes is
      feasible by NIRF imaging using a cystein-protease sensitive optical probe.

PMID- 12802616
TI  - MR imaging-guided axillary node biopsy for breast cancer: initial findings.
AB  - The aim of this study was to evaluate the usefulness and feasibility of
      preoperative sentinel node needle biopsy of the breast under guidance of open MR
      imaging, a method that we developed. Nine patients with breast cancer in whom the
      axillary lymph nodes were not palpable underwent preoperative sentinel node
      needle biopsy under real-time MR imaging guidance. The sentinel nodes were
      identified before the biopsy using CT and MR imaging. Diagnostic ability of this
      method was compared with that of the operative diagnosis. Sentinel nodes were
      correctly identified in all 9 patients. The MR imaging-guided sentinel node
      needle biopsy was performed for all of the 9 patients, and, in 7 (77.8%) of the
      9, a specimen sufficient for pathologic evaluation was obtained; and in 6,
      whether malignancy existed was precisely diagnosed. No serious complications were
      noted. This experience indicates the possibility of a precise diagnosis of
      whether the sentinel node in breast cancer is benign or malignant without
      surgery.

PMID- 12802617
TI  - Anterior axial ultrasound in monitoring infants with Pavlik harness.
AB  - Real-time ultrasonography has been used for diagnosis and screening of
      developmental dysplasia of the hip for several years. If diagnostic criteria are
      well established, the use of sonography in follow-up of treated infants remains
      extremely variable. The aims of this study were (a). to describe the normal
      sonographic anatomy of the infant abducted hip on an anterior axial view, and
      (b). to define the role of this approach in the follow-up of developmental
      dysplasia treated by Pavlik harness. Thirty-eight patients with Pavlik harness
      had anterior axial sonograms in addition to their usual clinical and sonographic
      follow-up. Normal anatomy was inferred from the examination of 25 clinically
      proven normal hips in the same population. The best criterion of a normal
      positioning of the femoral head appears to be the alignment of the pubic bone and
      the femoral metaphysis. Pavlik harness was the only treatment in 32 patients. It
      was directly efficient in 22, after readjustment in 10 patients. Reduction was
      shown by anterior sonography in all of them. In 6 children, sonography showed no
      reduction and subsequent treatment by closed or open reduction was carried out.
      Anterior axial sonogram can show reduction of a dislocated hip in children with
      Pavlik harness, but it does not evaluate its stability. It helps optimize the
      settings of the harness, and may predict a poor outcome, but it does not identify
      the cause of non-reducibility.

PMID- 12802618
TI  - Multiplex PCR for simultaneous detection of enterococcal genes vanA and vanB and
      staphylococcal genes mecA, ileS-2 and femB.
AB  - The experimental transfer of the vanA gene cluster from Enterococcus faecalis to
      Staphylococcus aureus has raised fears about the occurrence of such genetic
      transfer in clinical isolates of methicillin-resistant staphylococci. Recently,
      infections by a S. aureus strain carrying the enterococcal vancomycin resistance
      vanA gene cluster were reported. The possible emergence and dissemination of
      these strains is a serious health threat and makes optimization of prevention
      strategies and fast detection methods absolutely necessary. In the present study,
      we developed a PCR protocol for simultaneous detection of enterococcal vanA and
      vanB genes, the staphylococcal methicillin and mupirocin resistance markers mecA
      and ileS-2, and identification of S. aureus. As no vancomycin-resistant S. aureus
      isolates were available for our study, we used mixtures of enterococcal and
      staphylococcal colonies that harbored the different resistance markers to show
      that these genes could be detected simultaneously. This protocol could be used to
      facilitate the detection and identification of predictable S. aureus or
      methicillin-resistant strains carrying vanA or vanB.

PMID- 12802619
TI  - A longitudinal follow-up using the high trans-scrotal approach for inguinal and
      scrotal abnormalities in boys.
AB  - The popular incision for surgical approach to pediatric inguinal pathologies has
      been the suprapubic transverse inguinal incision. Yet alternative incisions may
      be considered. A prospectively randomized study of a consecutive series of 256
      male infants and children with various inguinal pathologies (mainly indirect
      inguinal hernias) were treated surgically using the "high trans-scrotal skin
      crease incision," over a period of 84 months (7 years) and were compared and
      found to be clinically better than age- and sex-matched 278 controls with
      suprapubic transverse inguinal incisions for wound healing/infection, edema,
      seroma, hematoma, malpositioning or atrophy of testes and recurrence of the
      primary pathology. The results in the study group were cosmetically and
      clinically more favorable, and better than the control group. Nosocomial
      infections, complications of incarceration, and emergency surgery have resulted
      in an acceptable morbidity rate of approximately 5%. Popularized use of the high
      trans-scrotal incision and further clinical experience is recommended to
      facilitate even better results.

PMID- 12802620
TI  - A novel incision for groin pathologies in children: the low inguinal groove
      approach.
AB  - BACKGROUND: The traditional approach to pediatric inguinal pathologies has been
      the suprapubic transverse inguinal incision. Alternative incisions for better
      cosmetic results may be considered. MATERIALS AND METHODS: The recently defined
      "low inguinal groove incision" was used in a consecutive series of 483 children
      having indirect groin hernias, hydroceles, and palpable undescended testes, etc.
      The neonates, infants, and children were operated on as elective day surgery
      cases. RESULTS: All children ended with excellent cosmetic and functional
      results. There were no complications or morbidity apart from a recurrence of an
      inguinal hernia in a 7 year-old boy. In addition to the series of girls reported
      earlier, this novel surgical incision has further been employed in boys with
      excellent results.

PMID- 12802622
TI  - Effects of a vegetable extract from Lupinus albus (LU105) on the production of
      matrix metalloproteinases (MMP1, MMP2, MMP9) and tissue inhibitor of
      metalloproteinases (TIMP1, TIMP2) by human gingival fibroblasts in culture.
AB  - This study examined the effects of a vegetable extract from Lupinus albus (LU105)
      on MMPs and TIMPs secreted by human gingival fibroblasts in culture. LU105 was
      extracted from seeds of L. albus and is freely soluble in water. Gelatin
      zymography showed that control human gingival fibroblasts maintained in culture
      for 48 h express pro-MMP2 (progelatinase A) in the culture medium while the
      active form of MMP2 (gelatinase A), the active form of MMP9 (gelatinase B), and
      pro-MMP9 (progelatinase B) are not detected. Fibroblasts derived from inflamed
      gingiva expressed in the culture medium increased amounts of pro-MMP2
      (progelatinase A) compared with controls and significant amounts of pro-MMP9
      (progelatinase B). LU105 diminished the expression by gingival fibroblasts
      derived from inflamed tissue of both pro-MMP2 and pro-MMP9. Furthermore LU105 did
      not modify the amount of TIMP2 expressed in culture by controls or by gingival
      fibroblasts derived from inflamed tissue. TIMP1 and MMP1 significantly decreased
      when LU105 was added in the culture media of gingival fibroblasts derived from
      inflamed tissue compared with control fibroblasts. Thus LU105 seems to offer an
      opportunity to restore a correct balance between MMP2, MMP9, MMP1, and their
      natural inhibitors, i.e., TIMP1 and TIMP2 in human inflamed gingiva.

PMID- 12802623
TI  - Two types of plastid ftsZ genes in the liverwort Marchantia polymorpha.
AB  - Two types of ftsZ genes (MpftsZ1 and MpftsZ2) were isolated from the liverwort
      Marchantia polymorpha by degenerate reverse transcription PCR. The MpFtsZ1 and
      MpFtsZ2 proteins are predicted to localize in chloroplasts. Genomic Southern
      analysis suggested that each ftsZ gene is a single-copy nuclear gene. Northern
      analysis confirmed that both genes are active. A phylogenetic tree constructed
      with the deduced MpFtsZ amino acid sequences suggests that MpFtsZ1 and MpFtsZ2
      can be classified into the plant chloroplastic FtsZ1 and FtsZ2 families,
      respectively. This result suggests that two ftsZ families exist universally in
      land plants. The determination of the intron structures of both MpftsZ genes
      supported this hypothesis. The transformation of a sense MpftsZ2 overexpression
      construct into M. polymorpha produced a large chloroplast phenotype in a
      transgenic plant. The mean number of chloroplasts was 38.2 (standard deviation,
      21.4; n = 200) in epidermal cells of wild-type plants, whereas the mean number of
      chloroplasts was 7.4 (standard deviation, 4.4; n = 200) in the transgenic plant.
      Southern analysis showed that the cauliflower mosaic virus 35S promoter- MpftsZ2
      construct was inserted in at least three positions. Northern analysis suggested
      that the high accumulation of MpftsZ2 mRNA blocked plastid division.
      Determination of the chlorophyll content and the chlorophyll fluorescence
      parameters suggested that the macrochloroplasts function like chloroplasts in
      wild-type plants under normal light conditions. However, the transgenic plant
      grew more slowly than did wild-type plants.

PMID- 12802624
TI  - Localization of sucrose synthase and callose in freeze-substituted secondary-wall
      stage cotton fibers.
AB  - Methods for cryogenic fixation, freeze substitution, and embedding were developed
      to preserve the cellular structure and protein localization of secondary-wall
      stage cotton (Gossypium hirsutum L.) fibers accurately for the first time.
      Perturbation by specimen handling was minimized by freezing fibers still attached
      to a seed fragment within 2 min after removal of seeds from a boll still attached
      to the plant. These methods revealed native ultrastructure, including numerous
      active Golgi bodies, multivesicular bodies, and proplastids. Immunolocalization
      in the context of accurate structure was accomplished after freeze substitution
      in acetone only. Quantitation of immunolabeling identified sucrose synthase both
      near the cortical microtubules and plasma membrane and in a proximal exoplasmic
      zone about 0.2 microm thick. Immunolabeling also showed that callose (beta-1,3
      glucan) was codistributed with sucrose synthase within this exoplasmic zone.
      Similar results were obtained from cultured cotton fibers. The distribution of
      sucrose synthase is consistent with its having a dual role in cellulose and
      callose synthesis in secondary-wall-stage cotton fibers.

PMID- 12802625
TI  - Multiple activities of a novel substance, dictyopyrone C isolated from
      Dictyostelium discoideum, in cellular growth and differentiation.
AB  - We report that a novel substance named dictyopyrone C (DPC) has remarkable
      effects on growth and differentiation of Dictyostelium discoideum Ax-2 cells, in
      a dose-dependent manner. In the presence of 3-15 microM DPC, differentiation of
      starving Ax-2 (clone MS) cells was greatly enhanced in submerged culture, when
      vegetative MS cells were harvested at the mid-late-exponential growth phase (>3 x
      10(6) cells per ml) and starved. In contrast, DPC above 30 microM markedly
      impaired the progression of differentiation including cell aggregation, most of
      starved cells being round after 3-4 h of DPC application and then lysed during
      further incubation. In the presence of 30 microM DPC however, MS cells that had
      been harvested at the early exponential growth phase (<5 x 10(5) cells per ml)
      and starved became neither round nor lysed and exhibited rather enhanced
      differentiation. Essentially the same results were obtained in cultures of
      starved cells on nonnutrient agar. With respect to the DPC effect on MS cells
      growing in axenic medium, cell lysis and growth inhibition by DPC at
      concentrations higher than 15 microM were realized in the mid-late-exponential
      growth-phase cells (>3 x 10(6) cells per ml) but not in the early-exponential
      growth-phase cells (<5 x 10(5) cells per ml). Moreover, analysis using
      synchronized MS cells has demonstrated that the DPC effect changes in a cell
      cycle-dependent manner. In contrast to such unique DPC actions, the pyrone ring
      of DPC had no effects on growth and differentiation within the range of 3-120
      microM tested. These findings strongly suggested the importance of the combined
      structure of the pyrone ring and the linear carbon chain in revelation of the DPC
      activities.

PMID- 12802627
TI  - Strict paternal transmission of mitochondrial DNA of Chlamydomonas species is
      explained by selection against maternal nucleoids.
AB  - The non-Mendelian inheritance of organelle DNA is common in most plants and
      animals. Here we examined inheritance mechanisms involved in the transfer of
      mitochondrial DNA. We successively backcrossed (to F(5)) two interfertile strains
      of the unicellular isogamous haploid algae Chlamydomonas reinhardtii and
      Chlamydomonas smithii to match nuclear backgrounds and examine transmission
      patterns of mitochondrial DNA by PCR analysis of cob gene sequences.
      Mitochondrial DNA was strictly transmitted paternally. To investigate the
      behavior of parental mitochondrial DNA, we used F(5) progeny to form zygotes and
      isolated single zygotes. The results showed selective disappearance of maternal
      mitochondrial nucleoids occurred between 3 and 6 h after zygote formation.

PMID- 12802626
TI  - Polarity establishment requires dynamic actin in fucoid zygotes.
AB  - Previous work has demonstrated that actin plays important roles in axis
      establishment and polar growth in fucoid zygotes. Distinct actin arrays are
      associated with fertilization, polarization, growth, and division, and agents
      that depolymerize actin filaments (cytochalasins, latrunculin B) perturb these
      stages of the first cell cycle. Rearrangements of actin arrays could be
      accomplished by transport of intact filaments and/or by actin dynamics involving
      depolymerization of the old array and polymerization of a new array. To
      investigate the requirement for dynamic actin during early development, we
      utilized the actin-stabilizing agent jasplakinolide. Immunofluorescence of actin
      arrays showed that treatment with 1-10 microM jasplakinolide stabilized existing
      arrays and induced polymerization of new filaments. In young zygotes, a cortical
      actin patch at the rhizoid pole was stabilized, and in some cells supernumerary
      patches were formed. In older zygotes that had initiated tip growth, massive
      filament assembly occurred in the rhizoid apex, and to a lesser degree in the
      perinuclear region. Treatment disrupted polarity establishment, polar secretion,
      tip growth, spindle alignment, and cytokinesis but did not affect the maintenance
      of an established axis, mitosis, or cell cycle progression. This study suggests
      that dynamic actin is required for polarization, growth, and division.
      Rearrangements in actin structures during the first cell cycle are likely
      mediated by actin depolymerization within old arrays and polymerization of new
      arrays.

PMID- 12802628
TI  - Cytological evidence for preservation of mitochondrial and plastid DNA in the
      mature generative cells of Chlorophytum spp. (Liliaceae).
AB  - Following 4',6-diamidino-2-phenylindole staining of mature pollen grains of
      Chlorophytum comosum, fluorescence microscopy confirmed that cytoplasmic
      nucleoids (DNA aggregates) were present in the generative cells, which indicated
      the possibility of biparental cytoplasmic inheritance. Electron and immuno
      electron microscopy showed that both plastids and mitochondria were present in
      the generative cells, and both organelles contained DNA. These results indicate
      that mitochondria and plastids of C. comosum have the potential for biparental
      inheritance. Similar results were obtained with mature pollen grains of C.
      chinense. Therefore, we conclude the coincident biparental inheritance for
      mitochondria and plastids in the members of the genus Chlorophytum.

PMID- 12802629
TI  - Possible involvement of energy metabolism in the change of cytoplasm organization
      induced by a protein phosphatase inhibitor, calyculin A, in root hair cells of
      Limnobium stoloniferum.
AB  - In root hair cells of Limnobium stoloniferum, transvacuolar strands disperse and
      cytoplasmic spherical bodies (CSBs) emerge upon treatment with a protein
      phosphatase inhibitor, calyculin A (CA), whose effects were previously shown to
      be canceled by simultaneous treatment of the cells with a nonselective protein
      kinase inhibitor, K-252a. CSB formation is also suppressed by latrunculin B (LB)
      or cytochalasin D, actin filament depolymerization drugs, or 2,3-butanedione
      monoxime, an inhibitor of myosin activity. To confirm the involvement of myosin
      activity in CSB formation induced by CA, we examined the effect of an inhibitor
      of energy metabolism, NaN3, on CSB formation in root hair cells pretreated
      simultaneously with CA and LB. In the presence of CA-LB, CSB formation was
      suppressed due to the depolymerization of actin filaments. When these drugs were
      removed, the actin filaments recovered and CSBs emerged even in the presence of K
      252a. These results indicated that the phosphorylation level in the cells is
      elevated during the CA-LB treatment and that a phosphorylation level sufficient
      for the CSB formation was sustained even after CA removal. On the other hand, CSB
      formation after simultaneous treatment with CA and LB was significantly
      suppressed in the presence of NaN3. In such cells, actin filament bundles
      recovered, although their organization was random. The present and previous
      results suggested that myosin activity is necessary for CSB formation induced by
      CA, and that myosin regulated by phosphorylation-dephosphorylation is implicated
      in the organization of the actin cytoskeleton in root hair cells.

PMID- 12802630
TI  - Involvement of microtubules in rhizoid differentiation of Spirogyra species.
AB  - Some species of Spirogyra form rosette-shaped or rod-shaped rhizoids in the
      terminal cell of the filaments. In the present study, we analyzed an involvement
      of microtubules (MTs) in rhizoid differentiation. Before rhizoid differentiation,
      cortical MTs were arranged transversely to the long axis of cylindrical cells,
      reflecting the diffuse growth. At the beginning of rhizoid differentiation, MTs
      were absent from the extreme tip of the terminal cell. In the other area of the
      cell, however, MTs were arranged transversely to the long axis of the cell. In
      the fully differentiated rosette-shaped rhizoid, MTs were randomly organized.
      However, at a younger stage of rosette-shaped rhizoids, MTs were sometimes
      arranged almost transversely in the lobes of the rosette. In the rod-shaped
      rhizoid, MTs were arranged almost transversely. MT-destabilizing drugs (oryzalin
      and propyzamide) induced swelling of rhizoids, and neither rosette-shaped nor rod
      shaped rhizoids were formed. The role of MTs in rhizoid differentiation was
      discussed.

PMID- 12802631
TI  - Behavior of storage lipids during development and germination of olive ( Olea
      europaea L.) pollen.
AB  - The presence of abundant oil bodies in the mature olive pollen grain has led us
      to focus on the behavior of these lipid bodies during pollen development and in
      vitro pollen germination. The appearance, increase, and accumulation of lipid
      bodies have been determined by following the sequential development of the pollen
      grain. Semithin slices of anthers and pollen grains were stained with Sudan Black
      B in order to identify neutral lipids. Ultrastructural studies were also carried
      out. Our results show a notable increase in lipid bodies between the young-pollen
      grain stage and the mature-pollen-grain stage. Substantial polarization of lipid
      bodies was observed after 1 or 2 h of pollen incubation in germination medium.
      During pollen tube growth, the lipid bodies are located near the germinative
      aperture after 3 h of incubation, as well as inside the pollen tube, thus
      suggesting that the lipid bodies move from the pollen grain to the pollen tube.
      After 7 h of germination the presence of lipid bodies inside the pollen tube is
      no longer substantial. Our results support the idea that lipid bodies are
      involved in pollen germination, stigma penetration, and pollen tube growth. These
      results are discussed in connection with their implications for the pollen
      germination process.

PMID- 12802632
TI  - Actomyosin is involved in the plasmolytic cycle: gliding movement of the
      deplasmolyzing protoplast.
AB  - The leaf cells of Chlorophytum comosum seem to have the ability to regulate their
      protoplast volume and shape during the plasmolytic cycle. This phenomenon was
      morphologically expressed by the stabilization of the plasmolyzed protoplast
      volume and shape within 1-5 min after the immersion of the leaf segments in the
      plasmolytic fluid and temporarily at the onset of deplasmolysis. During the
      latter stage the plasmolyzed protoplast rounded up and assumed a perfectly convex
      shape and glided into the cell lumen along the cell axis. This gliding movement
      was active, nonsaltatory, and conducted with a constant velocity and lasted for a
      short time. During this movement the protoplast volume did not change
      appreciably. As far as we know, this movement has not been described so far.
      Deplasmolysis proceeded and was rapidly completed when the protoplast stopped
      moving. Leaf cells which have been affected by an antiactin filament drug or
      myosin inhibitors lost their ability to regulate the volume and shape of the
      plasmolyzing protoplast. In addition, the gliding protoplast movement was also
      inhibited in the treated cells. These data show for the first time that the
      actomyosin system is involved in the mechanism of volume regulation during the
      plasmolytic cycle and that it underlies the gliding movement of the
      deplasmolyzing protoplast.

PMID- 12802633
TI  - Postmeiotic cytokinesis and pollen aperture number determination in eudicots:
      effect of the cleavage wall number.
AB  - In eudicot postmeiotic tetrads, apertures are usually joined in pairs in highly
      conserved areas. These appear to be located at the last points of contact
      persisting at the end of cytokinesis between the cytoplasm of the future
      microspores. In order to investigate the relationship between cytokinesis and
      aperture formation, aperture distribution within postmeiotic tetrads and the
      progression of meiosis were studied in Nicotiana tabacum cv. Ambalema. This
      variety (inbred line) produces about 85% tricolporate pollen and 15%
      tetracolporate pollen grains. In addition, about 7% of tetrads are composed of
      four equal-sized microspores and a supernumerary pseudomicrospore of small size
      and an equal proportion of tetrads exhibit unpaired apertures (these apertures
      are not joined in pairs within tetrads). Observation of cytokinesis indicates
      that both unpaired apertures and pseudomicrospores could result from the
      persistence of late communications between microsporocytes. Observations of
      tetrads indicate that an increase in the number of elements that are separated
      during cytokinesis is correlated with an increase in microspore aperture number.
      All data converge to support the hypothesis that aperture site determination is
      partly controlled by the number of walls formed to separate the different
      elements of the tetrad.

PMID- 12802635
TI  - Cytoskeletal 10 nm filaments in cells of the algal phyla Chlorophyta, Charophyta,
      and Chrysophyta and their developmentally regulated and species-specific
      association with prosomes.
AB  - 10 nm diameter filaments were observed in whole-mount preparations of algae of
      diverse phyla: Acetabularia acetabulum and A. major (Chlorophyta), Chara
      australis and Nitella flexilis (Charophyta), and Poterioochromonas malhamensis
      (Chrysophyta). A polyclonal antibody raised against a basic, 50 kDa DNA-binding
      protein of A. acetabulum stains the filaments of A. acetabulumand and A. major as
      well as of C. australis and N. flexilis. While in the perinuclear region of A.
      acetabulumand and A. major and throughout the cytoplasm of P. malhamensis the 10
      nm filaments have a smooth appearance, in the stalk of A. acetabulumand and A.
      major they are densely covered by globular structures; in C. australis and N.
      flexilis they are less frequently associated with such material. The morphology
      of a part of the globular particles is quite reminiscent of prosomes. A
      monoclonal antibody elicited against prosomes isolated from A. acetabulum indeed
      decorates the globular particles on the A. acetabulum and A. major filaments. The
      possible role of these filament-particle associations is discussed.

PMID- 12802634
TI  - Iron deficiency enhances the levels of ascorbate, glutathione, and related
      enzymes in sugar beet roots.
AB  - The effects of Fe deficiency stress on the levels of ascorbate and glutathione,
      and on the activities of the enzymes ferric chelate reductase, glutathione
      reductase (EC 1.6.4.2), ascorbate free-radical reductase (EC 1.6.5.4) and
      ascorbate peroxidase (EC 1.11.1.11), have been investigated in sugar beet ( Beta
      vulgaris L.) roots. Plasma membrane vesicles and cytosolic fractions were
      isolated from the roots of the plants grown in nutrient solutions in the absence
      or presence of Fe for two weeks. Plants responded to Fe deficiency not only with
      a 20-fold increase in root ferric chelate reductase activity, but also with
      moderately increased levels of the general reductants ascorbate (2-fold) and
      glutathione (1.6-fold). The enzymes of the ascorbate-glutathione cycle in roots
      were also affected by Fe deficiency. Glutathione reductase activity was enhanced
      1.4-fold with Fe deficiency, associated to an increased ratio of reduced to
      oxidized glutathione, from 3.1 to 5.2. The plasma membrane fraction from iron
      deficient roots showed 1.7-fold higher ascorbate free-radical reductase activity,
      whereas in the cytosolic fraction the enzyme activity was not affected by Fe
      deficiency. The activity of the cytosolic hemoprotein ascorbate peroxidase
      decreased approximately by 50% with Fe deprivation. These results show that sugar
      beet responds to Fe deficiency with metabolic changes affecting components of the
      ascorbate-glutathione cycle in root cells. This suggests that the ascorbate
      glutathione cycle would play certain roles in the general Fe deficiency stress
      responses in strategy I plants.

PMID- 12802636
TI  - Lumbosacral fusion using the Boucher technique in combination with a
      posterolateral bone graft.
AB  - This study evaluates the clinical and radiological results of using the facet
      screw fixation technique described by Boucher in combination with a
      posterolateral fusion rather than a posterior fusion for symptomatic degenerative
      disease of the lumbosacral junction. It is a retrospective review of 38
      consecutive patients with an average follow-up of 28 months. Radiologically, all
      patients had a solid fusion. Clinically, 23 patients (60%) had excellent results,
      11 patients (29%) good results, 3 patients (8%) fair results and 1 patient (3%)
      had a poor result. There were no neurological complications. The findings support
      the view that the Boucher technique of facet joint fixation in combination with a
      posterolateral fusion is a safe and effective method of dealing with chronic
      symptoms relating to degenerative changes at the lumbosacral junction. The
      authors stress the importance of patient selection and attention to operative
      technique if the clinical results are to correlate with the results of fusion.

PMID- 12802637
TI  - Vesicoureteral reflux: comparison between urosonography and radionuclide
      cystography.
AB  - Our aim was to compare contrast-enhanced color Doppler voiding urosonography
      (VUS) and direct radionuclide voiding cystography (DRVC) to determine the
      usefulness of ultrasonography (US) in the detection and grading of vesicoureteral
      reflux (VUR). In this study, the two techniques were performed simultaneously on
      a group of 64 children referred for the evaluation of VUR. DRVC detected VUR in
      54/128 ureterorenal units, and VUS confirmed reflux in 44 (81%). Only in two
      cases was the reflux not confirmed by DRVC (97% specificity). Ten units with
      minimal grade I VUR detected by DRVC were not identified by VUS. For
      identification of grade II and III reflux, sensitivity of VUS reached 100%. Ten
      units with grade I VUR at DRVC presented grade II at VUS. Eleven units with grade
      II VUR at DRVC presented grade III at VUS. In conclusion, contrast-enhanced VUS
      is a useful diagnostic tool for the detection of VUR in children. Our data
      suggest a higher diagnostic accuracy of urosonography compared to radionuclide
      cystography in the determination of the grade of VUR; this may have significant
      consequences on the management of young patients affected by VUR.

PMID- 12802638
TI  - Expression of glucocorticoid receptors in mononuclear cells in nephrotic
      syndrome.
AB  - Coulter flow cytometry was used to determine glucocorticoid receptors (GCR) in
      the peripheral blood cells of patients with nephrotic syndrome. The expression of
      GCR in the lymphocytes (CD3/GCR) and monocytes (CD14/GCR) of peripheral blood of
      23 (age 4.9+/-2.7 years) children with steroid-sensitive nephrotic syndrome was
      assessed before treatment (proteinuria >50 mg/kg per 24 h), after 4-6 weeks of
      prednisone treatment, without proteinuria, and in remission, without proteinuria
      and without any treatment. Before treatment the expression of CD3/GCR was 61.8+/
      18.3% and CD14/GCR 43.6.8+/-20.3%; this did not differ from the results of the
      normal control group ( P>0.05). However, after treatment GCR expression in
      lymphocytes was 50% ( P<0.001) and in monocytes about 20% lower ( P<0.05). In
      remission, the GCR expression increased and did not differ from the results
      before treatment ( P>0.05). A positive correlation between the serum cortisol
      concentration and the expression of CD3/GCR was found ( r=0.504, P=0.02). In
      summary, we report that in children with steroid-sensitive nephrotic syndrome,
      prednisone treatment causes the temporary decrease of the expression of GCR in
      lymphocytes. A positive correlation between GCR expression and serum cortisol was
      found. A decrease in GCR expression in monocytes did not correlate with cortisol
      concentration.

PMID- 12802639
TI  - Lymphomatoid granulomatosis in a renal transplant patient.
AB  - Lymphomatoid granulomatosis is a rare angiocentric and angiodestructive pulmonary
      angiitis considered as a variant of the lymphoproliferative disorder group.
      Patients with organ transplantation are at an increased risk for post-transplant
      lymphoproliferative disorders secondary to their immunosuppression. However,
      lymphomatoid granulomatosis has rarely been described in patients with renal
      transplantation. It often presents with severe pulmonary signs. We describe a
      case whose initial presentation was an isolated VIth nerve palsy. We review the
      radiological and pathological findings and discuss the etiopathogenesis and
      therapeutic options of this particular lymphoproliferative disorder. With careful
      and stepwise reduction in her immunosuppression, our patient showed a complete
      disappearance of her lymphomatoid granulomatosis, and she is clinically well more
      than 3 years after the diagnosis, with good kidney function.

PMID- 12802640
TI  - BK virus-associated renal problems--clinical implications.
AB  - BK virus (BKV), a human polyomavirus, infects most of the human population, but
      clinically relevant infections are usually limited to individuals who are
      immunosuppressed. After primary infection, BKV remains latent in the kidneys and
      can be reactivated in immune deficiency conditions, including transplantation. As
      primary infection occurs in childhood, BKV may be particularly important in the
      pediatric transplant population. BKV is associated with tubulointerstitial
      nephritis and ureteric stenosis in renal transplant recipients and hemorrhagic
      cystitis in bone marrow transplant recipients. There are increasing reports of
      BKV causing nephropathy and cystitis in non-renal solid organ transplant
      recipients and other immunodeficiency diseases. This might be related to the use
      of more potent immunosuppressive regimens or increasing awareness of BKV as an
      important pathogen. Diagnosis of BKV disease is by biopsy. Histopathological
      changes in renal biopsy specimens may mimic rejection or drug toxicity, but BKV
      nuclear inclusions can be seen. Treatment is by reduction of immunosuppression.
      Antiviral agents such as cidofovir are showing promise. BKV DNA polymerase chain
      reaction in blood or biopsy may be helpful in monitoring therapy. The impact of
      BKV disease in children is not well understood and prospective studies are needed
      to elucidate this further. This article reviews the current understanding of BKV
      associated renal problems.

PMID- 12802641
TI  - Technique for introducing large composite mesh while performing laparoscopic
      incisional hernioplasty.

PMID- 12802642
TI  - Long-term outcome and health-related quality of life after laparoscopic and open
      colectomy for benign disease.
AB  - BACKGROUND: The benefits of laparoscopic colectomy (LC) vs open colectomy (OC)
      for the treatment of benign disease have not yet been clearly demonstrated with
      regard to long-term consequences and health-related quality of life (HRQL). The
      aim of this study was to compare LC and OC in terms of outcome and HRQL and to
      determine whether a generic nonspecific instrument for HRQL assessment is valid
      in postoperative follow-up. METHODS: Forty-nine patients who underwent LC for
      elective right hemicolectomy (RH) or sigmoid resection (SR) for benign polyps or
      uncomplicated diverticular disease between 1992 and 2000 were evaluated and
      compared to 50 controls treated by OC in the same period. All patients were
      evaluated by postal questionnaire to determine recurrence rates and surgery
      related complications. HRQL was assessed by the SF-36 Physical and Mental
      Component Summary Score (PCS, MCS) and by the SF-36 Health Survey, which measures
      eight different health-quality domains, including physical and social functioning
      (PF, SF), general health perception (GH), physical and emotional role limitations
      (RP, RE), body pain (BP), vitality (VT), and mental health (MH). RESULTS: The LC
      and OC patients were similar in age, gender, body mass index (BMI), American
      Society of Anesthesiologists (ASA) classification, and diagnosis. There were
      significant differences between the two groups in resection type (26 RH:23 SR in
      LC vs 16 RH:34 SR in OC, p = 0.03) and length of follow-up (median, 39 and 53.5
      months, respectively, p = 0.04), but neither parameter was predictive of the main
      SF-36 scores (PCS and MCS). There were no differences between the groups in
      recurrence rates (8% in LC vs 11% in OC) or surgery-related complications,
      including incisional hernias (16.3% in LC vs 17% in OC) and small bowel
      obstructions (2% in LC vs 10.4% in OC). None of the eight SF-36 Health Survey
      domains or the PCS or MCS scores showed significant differences between LC and OC
      patients in HRQL. However, occurrence of hernia after surgery was predictive of
      lower SF-36 scores, specifically in PF (p = 0.047), GH (p = 0.045), SF (p =
      0.047), MH (p = 0.041), and MCS (p = 0.037). In addition, small bowel obstruction
      was significantly associated with lower scores in BP (p = 0.008), GH (p = 0.008),
      SF (p = 0.013), RE (p = 0.026), MH (p = 0.003), and MCS (p = 0.003). CONCLUSION:
      LC was not different from OC for selected indications that measure long-term
      outcome and HRQL. SF-36 appears to be an appropriate instrument to measure
      postoperative HRQL, showing responsiveness to changes in objective outcome
      measures.

PMID- 12802643
TI  - Redefining gastroesophageal reflux (GER).
AB  - BACKGROUND: The detection of gastroesophageal reflux (GER) has to date been
      limited to acid exposure observed on 24-h pH monitoring. It is clear, however
      that nonacid reflux can be a significant clinical problem. Recently, as impedance
      technology with the capacity to detect all types of reflux (acid, nonacid,
      liquid, mixed, and air) has been developed. METHODS: Seventeen asymptomatic
      healthy volunteers underwent combined 24-h pH and impedance testing. In all
      patients, pH was measured at 5 cm above the lower esophageal sphincter (LES), and
      simultaneous impedance changes were recorded at 3, 5, 7, 9, 15, and 17 cm above
      the LES. Refluxes were classified as acid (drop in pH <4 for >5 sec), Nonacid,
      short acid, or nonacid delta based on chemical properties; they were further
      classified as liquid, mixed, or gas based on the physical refluxate detected by
      impedance changes. The height of the reflux entering the esophagus was classified
      as distal (<5 cm), intermediate (5-9 cm), or proximal (9-17 cm). RESULTS: A total
      of 868 reflux events were characterized. Fifty-nine percent of them were not
      conventional acid reflux and could only be detected by impedance changes. Less
      than 2% of the events that were detected by a fall in pH to <4 were not detected
      by impedance changes. Pure liquid reflux was seen in 35.4%, a mixed pattern in
      36.3%, and a gas reflux in 26.7%. Liquid was confined to the distal esophagus in
      30%; it reached the midesophagus in 58% and the proximal esophagus in 11%.
      CONCLUSIONS: Over half of GER events are not detected by pH studies. Liquid
      reflux reaches the mid and proximal esophagus 69% of the time and gas nearly
      always does (92%). The additional information provided by impedance technology is
      likely to have a major impact on the understanding and clinical management of
      patients with gastroesophageal reflux disease (GERD).

PMID- 12802644
TI  - A prospective randomized study of prophylactic antibiotics in elective
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Elective laparoscopic cholecystectomy (LC) has a low risk for
      infective complications, but many surgeons still use prophylactic antibiotics.
      The use of prophylactic antibiotics for LC is inconsistent and varies widely
      among surgeons. METHODS: We performed a prospective double-blind randomized study
      of prophylactic antibiotics in elective LC. Antibiotics were was given first
      before the operation and then again 24 h afterward. Group A ( n = 49) received 2
      g of cefotaxime; group B ( n = 43) received 10 ml of isotonic sodium chloride
      solution. A sample of bile was withdrawn by direct gallbladder puncture for
      anaerobic and aerobic cultures. Age, sex, weight, duration of surgery (DOS),
      presence of diabetes mellitus, American Society of Anesthesiologists (ASA)
      classification, gallbladder rupture, bile and/or stone spillage, gallbladder
      histological findings, findings from bile cultures positive for bacteria,
      episodes of colic within 30 days before surgery, length of stay (LOS), and number
      of septic complications were recorded for both groups. RESULTS: There was no
      differences between the two groups in terms of sex, weight, DOS, ASA score,
      gallbladder rupture, bile and/or stone spillage, gallbladder histological
      findings, findings from bile cultures positive for bacteria, or LOS. One
      infection occurred in the antibiotic prophylaxis group (2.04%); in the patients
      not receiving antibiotics, there was one other infection (2.32%). There was no
      statistical difference between the two groups in infective complications.
      CONCLUSION: In patients undergoing elective LC, antibiotic prophylaxis is
      justified only in high-risk patients. In all other patients, antibiotic
      prophylaxis does not seem to affect the incidence of postoperative infective
      complications. In low-risk patients, eliminating the unnecessary use of
      prophylactic antibiotics would result in a cost reduction; moreover, it would
      lower the risk of adverse reaction and reduce microbial resistance.

PMID- 12802645
TI  - Early postnatal behavior deficits after maternal carbon dioxide pneumoperitoneum
      during pregnancy.
AB  - BACKGROUND: In this study, we tested the hypothesis that maternal
      pneumoperitoneum produces early postnatal behavior deficits in the offspring.
      METHODS: Time-dated pregnant guinea pigs were exposed to 45 min of carbon dioxide
      (CO2) pneumoperitoneum at a pressure of 7 mmHg. There was no manipulation of the
      control animals. On postnatal days (PND) 10 and 20, the behavior of their
      offspring was assessed by monitoring the locomotor activity of each of the pups
      in a 1 x 1 m chamber demarcated into 100 squares. Locomotor data was log
      transformed and expressed as mean values (SD). RESULTS: At PND 10,
      pneumoperitoneum offspring exhibited significantly higher levels of locomotor
      activity than the offspring of controls (1.81 +/- 0.48 vs 1.33 +/- 0.78). The
      pneumoperitoneum pups continued to exhibit hyperactive behavior at PND 20 (1.83
      +/- 0.72 vs 1.20 +/- 0.72). CONCLUSIONS: Maternal pneumoperitoneum produces
      postnatal hyperactivity in guinea pig offspring, suggesting that there may be
      long-term consequences associated with the physiologic changes produced in the
      fetus during CO2 insufflation.

PMID- 12802647
TI  - Risk for laparoscopic fenestration of liver cysts.
AB  - BACKGROUND: Laparoscopic fenestration is considered the best treatment for
      symptomatic simple liver cysts. Conversely, the laparoscopic approach for the
      management of hydatid simple liver cysts is not widely accepted because of the
      risk for severe complications. Despite improvement in imaging techniques, the
      probability of preoperatively mistaking a hydatid liver cyst for a simple liver
      cyst remains about 5%. Therefore, laparoscopic fenestration, planned for a liver
      cyst could be performed unintentionally for an undiagnosed hydatid liver cyst.
      METHODS: From January 2000 to January 2001, 15 patients with a diagnosis of liver
      cyst underwent laparoscopy for fenestration. In all cases preoperative serologic
      and imaging assessment had excluded hydatid liver cyst. To further exclude
      hydatid liver cyst, preliminary aspiration of the cyst with assessment of cystic
      fluid characteristics was performed. RESULTS: In two patients with presumedly
      simple liver cyst, hydatid liver cyst was diagnosed instead at laparoscopy by
      aspiration of cystic fluid. The procedure was converted to laparotomy with
      subtotal pericystectomy. CONCLUSIONS: The risk of misdiagnosing a hydatid liver
      cyst for a simple liver cyst, especially in the presence of a solitary cyst,
      should be considered before laparoscopic fenestration is performed.
      Intraoperative aspiration of cyst fluid before fenestration can minimize this
      risk, thus avoiding severe intraoperative and late complications.

PMID- 12802646
TI  - Safety and efficacy of laparoscopic radiofrequency ablation of hepatocellular
      carcinoma in patients with liver cirrhosis.
AB  - BACKGROUND: The optimal treatment for hepatocellular carcinoma (HCC) is surgical
      resection. However, only a small percentage of patients are operative candidates.
      Percutaneous radiofrequency interstitial thermal ablation (RITA) has been shown
      to be efficacious in the treatment of unresectable HCC. Recent advances in
      laparoscopic ultrasound have greatly improved the accuracy in detecting
      intrahepatic HCC nodules, many of which were missed by computed tomography. Our
      objective was to introduce a novel operative combination of laparoscopic
      ultrasound with laparoscopic RITA in the treatment of HCC. METHODS: Eighty-eight
      patients with HCC in liver cirrhosis were submitted to laparoscopic RITA under
      sonographic guide. Most patients were in Child's A class of liver function.
      Patients with large tumors (> 5 cm), portal vein thrombosis, or severe liver
      disease (Child's C class) were excluded. RESULTS: The laparoscopic RITA procedure
      was completed in 86 of 88 patients (98% feasibility rate). Laparoscopy with
      laparoscopic ultrasound identified 23 new malignant lesions (27%) in comparison
      with the results of preoperative imaging. A total of 127 lesions were treated by
      RITA. There was no operative mortality. Sixty-one patients had no complication
      (71%). After a mean follow-up of 14.3 +/- 11.6 months, a complete response with a
      100% necrosis was achieved in 70 of 83 patients examined (86%). During follow-up,
      9 patients (11%) locally recurred at the RITA site and 38 patients (46%) had new
      malignant nodules. CONCLUSIONS: Laparoscopic RITA of HCC proved to be a safe and
      effective technique in the short term. This technique may be indicated when the
      percutaneous approach to the lesion is very difficult or if the patient is too
      ill to undergo laparotomy.

PMID- 12802648
TI  - CO2 promotes plasminogen activator inhibitor type 1 expression in human
      mesothelial cells.
AB  - BACKGROUND: Previous observations have indicated that CO2 insufflation increases
      peritoneal plasminogen activator inhibitor type 1 (PAI-1) expression. METHODS:
      Primarily cultured human peritoneal mesothelial cells were exposed to either
      flowing or pressurized CO2 for 90 min. Unexposed cultures served as controls.
      Samples of cell culture media were taken at 0, 5, and 24 h after exposure to
      measure media pH, PAI-1, and tissue-type plasminogen activator (t-PA) protein
      release. Simultaneous samples were taken to measure PAI-1 and t-PA mRNA
      expression. RESULTS: Mesothelial cells exposed to flowing CO2 released more PAI-1
      than those exposed to pressurized CO2 ( p < 0.001) and controls ( p < 0.001).
      Cells exposed to flowing CO2 had an increased PAI-1 mRNA expression at 5 h.
      CONCLUSIONS: CO2 increased mesothelial cell PAI-1 expression involving a
      transcriptional mechanism. These findings might provide a mechanism for adhesion
      formation and cancer progression following laparoscopic surgery.

PMID- 12802649
TI  - Abdominal symptoms: do they disappear after cholecystectomy?
AB  - OBJECTIVE: To evaluate the effect of cholecystectomy in patients with gallstones
      on preoperative abdominal symptoms. METHODS: A systematic search was made of the
      Medline database in combination with reference checking. Articles were excluded
      if patients aged <18 years, symptom relief rates could not be calculated, if
      follow-up after cholecystectomy was less than 1 month, or when the included
      patients were at extraordinary risk for a complicated outcome. Potential
      differences in relief rates due to patient selection, retrospective versus
      prospective design, duration of follow-up, or intervention were analyzed using
      logistic regression. RESULTS: The pooled relief rate for "biliary pain" was high
      92% (95% confidence interval 86 to 96%). Symptom relief rates were consistently
      higher in studies that included acute cholecystectomies. For upper abdominal pain
      -without restrictions for intensity or duration--pooled relief rates ranged from
      72% (66 to 77%) after elective cholecystectomy, to 86% (83 to 91%) after acute
      cholecystectomy. The relief rate of food intolerance was higher in studies with a
      follow-up < or =12 months (88%, 76 to 91%) compared to studies with a follow-up
      of more than 12 months (65%, 55 to 74%). CONCLUSION: In almost all patients with
      gallstones biliary pain disappeared after cholecystectomy. There is insufficient
      evidence, however, that this relief was due to cholecystectomy. Relief rates of
      other isolated symptoms were low in patients with an elective cholecystectomy. A
      proper evaluation of the effectiveness of cholecystectomy in terms of abdominal
      symptom relief rates requires a randomized trial.

PMID- 12802650
TI  - Depth cue reliance in surgeons and medical students.
AB  - BACKGROUND: Depth perception is reduced in endoscopic surgery, although little is
      known about the effect this has on surgical performance. METHODS: To assess the
      role of depth cues, 45 subjects completed tests of depth cue reliance. Surgical
      skill was assessed using the Minimally Invasive Surgical Trainer-Virtual Reality,
      a previously validated laparoscopic simulator. RESULTS: We could demonstrate no
      difference in cue reliance for three depth cues--namely stereo, texture, and
      outline--between surgeons and medical students. Greater dominance on stereo for
      medical students was a positive finding and a negative finding for the surgeons
      when correlated with surgical performance. CONCLUSIONS: We suggest that surgeons
      learn to adapt to the nonstereo environment in MIS, and this is the first study
      to show evidence of this phenomenon. This difference in stereo reliance is a
      reflection of the experience that surgeons have with laparoscopy compared with
      medical students, who have none.

PMID- 12802651
TI  - Percutaneous fetoscopic tracheal balloon occlusion in sheep.
AB  - BACKGROUND: In order to minimize maternal trauma from current techniques for
      temporary fetoscopic tracheal occlusion, we tried to develop a percutaneous
      fetoscopic technique in sheep. METHODS: In nine ewes between 77 and 128 days of
      gestation, the amniotic cavity was entered percutaneously. Each fetus was
      positioned and the feasibility of fetal laryngoscopy and percutaneous fetoscopic
      tracheal balloon occlusion was assessed. RESULTS: Percutaneous intraamniotic
      access, fetal positioning, oropharyngeal sheath insertion, and fetoscopic
      laryngoscopy were achieved in all nine fetal sheep. Following some technical
      modifications to the working channel of the fetoscope, percutaneous fetoscopic
      tracheal balloon occlusion was successfully achieved in the last seven sheep.
      CONCLUSION: Percutaneous fetoscopic balloon occlusion of the fetal trachea can
      effectively and safely be achieved in sheep. Because intraamniotic spatial
      relationships, fetal position, and umbilical cord length are technically less
      favorable in sheep, our operative techniques might be feasible in humans even if
      difficult intraamniotic conditions are encountered.

PMID- 12802653
TI  - Prospective randomized trial of laparoscopic (transabdominal preperitoneal) vs
      open (mesh) repair for bilateral and recurrent inguinal hernia.
AB  - BACKGROUND: Laparoscopic hernia repair excites controversy because its benefits
      are debatable and critics claim it is attended by serious complications. The one
      group of patients in whom benefits may outweigh the perceived disadvantages are
      those with bilateral or recurrent inguinal hernias. METHOD: One hundred twenty
      patients with bilateral or recurrent hernias were randomized to either
      laparoscopic transabdominal preperitoneal (TAPP) or open mesh repair. Patients
      completed a well-being questionnaire prior to and following surgery together with
      a visual analog pain score. Patients were followed up clinically at 1 and 3
      months and thereafter by their general practitioner. RESULTS: Age and sex
      distribution was similar in the two groups. Laparoscopic TAPP hernia was quicker
      (40 vs 55 min; p < 0.001), less painful (visual analog pain score, 2.8 vs 4.3; p
      = 0.003) and allowed earlier return to work (11 vs 42 days; p < 0.001) compared
      to open mesh repair. CONCLUSION: This trial demonstrates that laparoscopic hernia
      repair via the TAPP route offers significant benefit to patients undergoing
      bilateral or recurrent inguinal hernia repair.

PMID- 12802652
TI  - Scoring system to predict asymptomatic choledocholithiasis before laparoscopic
      cholecystectomy. A matched case-control study.
AB  - BACKGROUND: The purpose of this prospective study was to evaluate if a recently
      proposed score system based on six preoperative parameters [history of colic pain
      and/or jaundice, dyspepsia, cholecystitis, ultrasound (US), evidence of common
      bile duct stones (CBDS), number and size of gallbladder stones at US, level of
      serum glutamic oxalacetic transaminase and/or alkaline phosphatase is effective
      in the selection of patients undergoing laparoscopic cholecystectomy (LC) with
      asymptomatic CBDS and could allow a significant reduction of the total number of
      preoperative examinations. METHODS: In the case group, 408 patients were
      categorized into low-, medium-, and high-risk classes and underwent,
      respectively, no further preoperative assessment of the bile duct, intravenous
      cholangiography (IVC), and endoscopic retrograde cholangiography (ERC).
      Intraoperative cholangiography (IOC) was performed whenever the surgeon was in
      doubt as to biliary anatomy or bile duct clearance. These patients were compared
      with 408 retrospectively matched patients (control group) undergoing routine
      preoperative IVC and/or ERC. RESULTS: In the case group, significantly lower
      numbers of IVC (120 vs 392) and IOC (3 vs 16) were performed ( p < 0.005),
      whereas no difference in the total number of ERCs was noted. One patient in the
      control group had retained CBDS detected during follow-up evaluation, whereas
      none occurred in the case group. CONCLUSION: The proposed scoring system allows
      selective use of IVC, ERC, and/or IOC in patients undergoing elective LC.

PMID- 12802654
TI  - A prospective endoscopic study of retropubic vascular anatomy in 121 patients
      undergoing endoscopic extraperitoneal inguinal hernioplasty.
AB  - BACKGROUND: A sound knowledge of retropubic pelvic vascular anatomy is pivotal to
      the successful performance of endoscopic total extraperitoneal (TEP) inguinal
      hernioplasty. The objective of the current study was to evaluate the incidence
      and anatomy of iliopubic and aberrant obturator vessels. METHODS: Between July
      2001 and March 2002, a prospective endoscopic evaluation of retropubic vascular
      anatomy was performed on patients who underwent TEP. Endoscopic photographs of
      the vasculature overlying the superior pubic ramus in the recruited patients were
      captured on a computer. RESULTS: The retropubic vascular anatomy of 121 patients,
      who underwent either unilateral (n = 100) or bilateral (n = 21) TEP was examined.
      The iliopubic artery and vein were invariably present in every patient, and
      traversed along the iliopubic tract toward the pubic symphysis. The aberrant
      obturator artery was present in 31 pelvic halves, giving an overall incidence of
      22%. The aberrant obturator vein existed between the external iliac and obturator
      venous system in 27% (n = 38) of the 141 pelvic halves examined. The overall
      incidence of corona mortis, in the form of either an aberrant obturator vein or
      artery, was 40% (n = 56). CONCLUSIONS: Iliopubic vein and artery are universal
      findings in every patient. Both aberrant obturator artery and vein cross the
      superior pubic rami, and are therefore susceptible to injuries during dissection
      of the Bogros space and stapling of the mesh onto Cooper's ligament. Awareness of
      these aberrant vessels will help to reduce bleeding and subsequent morbidity.
      Tracing along the aberrant vessel can easily identify the obturator foramen,
      which is an anatomic landmark that indicates an adequate inferior dissection of
      the preperitoneal space.

PMID- 12802655
TI  - Seroma following endoscopic extraperitoneal inguinal hernioplasty.
AB  - BACKGROUND: Because it mimics a postoperative recurrence of hernia, seroma has
      been a concern to patients. There has been no consensus on the management of this
      condition after endoscopic totally extraperitoneal inguinal hernioplasty (TEP).
      The objectives of the present study were to evaluate the incidence and treatment
      of seroma after TEP. Risk factors for the development of seroma were also
      examined. METHODS: A total of 450 consecutive patients who underwent TEP between
      June 1999 and May 2002 were recruited. All data were collected prospectively. The
      outcomes of patients who developed seromas were compared to those without this
      postoperative complication. Regression analysis was performed to identify
      independent risk factors for seroma formation. RESULTS: The overall incidence of
      seroma formation was 7.2% ( n = 40). The postoperative recovery of patients was
      not influenced by the development of seroma. The mean size of the seromas was 3.8
      cm. Adopted treatment strategies included observation ( n = 29), oral lysozyme (
      n = 10), and percutaneous aspiration ( n = 3), but neither of the two
      interventions appeared to be effective. The seromas resolved spontaneously by an
      average of 2.4 (mean) months. Significant clinical factors associated with seroma
      formation included old age, large hernial defects, an extension of the hernia
      into the scrotum, and the presence of a residual distal indirect sac. By logistic
      regression, a large hernial defect and an extension of the hernia into the
      scrotum were found to be independent risk factors for seroma formation.
      CONCLUSIONS: Although seroma is a frequent minor morbidity after TEP, it has no
      impact on postoperative recovery. Because all seromas invariably resolve,
      expectant treatment with observation is recommended. Inguinoscrotal hernia
      carries a four-fold increased risk of developing seroma after TEP.

PMID- 12802656
TI  - Unusual presentations of spilled gallstones.
AB  - Perforation of the gallbladder with resultant spillage of gallstones is not an
      uncommon occurrence. Spillage is reported to occur in 6% to 40% of laparoscopic
      cholecystectomies. Although not generally considered a significant problem,
      retained gallstones may cause serious complications years after the operation,
      with a clinical presentation that often is confusing. We report two cases of
      unusual complications from spilled gallstones. The first patient presented with
      clinical and radiologic findings of acute appendicitis 8 years after the
      laparoscopic cholecystectomy. The second patient presented with spontaneous
      erosion of spilled gallstones through the back 2 years and 9 months after the
      laparoscopic cholecystectomy. The literature is reviewed, and the management of
      spilled gallstones is discussed briefly. Although the complication rate is low,
      every effort should be made to retrieve spilled gallstones, and the event should
      be recorded in detail in the operative record. Obligatory conversion to an open
      procedure is not necessary.

PMID- 12802657
TI  - Increased transperitoneal bacterial translocation in laparoscopic surgery.
AB  - BACKGROUND: The indications for laparoscopic surgery have expanded to include
      diseases possibly associated with peritonitis such as appendicitis, perforated
      peptic ulcers, and diverticulitis. The safety of carbon dioxide (CO2)
      pneumoperitoneum in the presence of peritonitis has not been proved. Our previous
      investigations demonstrated increased bacteremia associated with CO2
      insufflation. In effort to clarify the relative effects of intraabdominal
      pressure and type of gas, this study was designed to measure bacterial
      translocation with different gases at different pressures of pneumoperitoneum.
      METHODS: For this study, 110 rats were given intraperitoneal bacterial
      innoculations with Escherichia coli and equally divided into five groups of 20
      animals each. The study groups included a control group with no pneumoperitoneum
      administered (n = 30), insufflation at a commonly used pressure of 14 mmHg with
      helium (n = 20) and CO2 (n = 20), and low insufflation at 3 mmHg with helium (n =
      20) and CO2 (n = 20) in an effort to minimize influences related to pressure.
      Blood cultures were checked at 15-min intervals for the first 45 min, then hourly
      thereafter for a total of 165 min after peritoneal inoculation with 2 x 10(7) E.
      coli. RESULTS: There is increased risk of bacterial translocation in comparing
      groups that underwent pneumoperitoneum with those that did not in the rat
      peritonitis model. Furthermore, these findings are dependent on the presence or
      absence of gas, but not necessarily on the type of gas used for insufflation. In
      the low-pressure groups of both gases (helium and CO2), bacterial translocation
      was significantly increased, as compared with the control group. Low pressure
      also was associated with increased bacterial translocation, as compared with high
      pressure, but beyond 30 min of insufflation, no significant differences were
      apparent. CONCLUSIONS: The risk of bacterial translocation in the E. coli rat
      peritonitis model is increased with insufflation using CO2 or helium, and this
      effect is more significant at lower pressures (3 mmHg) than at higher pressures
      (14 mmHg). However, no clinically applicable conclusions regarding the relative
      effects from type of gas or insufflation pressures could be confirmed.

PMID- 12802658
TI  - Endoscopic sphincterotomy for cholangitis after recent coronary artery bypass
      graft surgery.
AB  - It is particularly attractive to perform endoscopic retrograde
      cholangiopancreatography (ERCP) with sphincterotomy for cholangitis due to common
      bile duct stone because of the increased morbidity and mortality of the
      alternative therapy of choledochal exploration. The safety of therapeutic ERCP
      after recent myocardial injury is unknown since there are only five previously
      reported cases. Three patients underwent therapeutic ERCP after recent coronary
      artery bypass graft surgery for indication of recent cholangitis due to
      choledochal stones. Initially, the cholangitis was managed medically in all
      patients. Endoscopic sphincterotomy (ES) was performed 11, 17, and 14 days after
      coronary artery bypass graft surgery. The calculi were successfully extracted by
      sweeping the choledochus with a balloon-tipped catheter or basket in all cases.
      During ERCP the vital signs remained stable; no cardiac arrhythmias, hemorrhage,
      or pulmonary complications occurred. Our study demonstrates that therapeutic ERCP
      is not absolutely contraindicated after recent myocardial injury and suggests
      that ES is preferable to surgery for cholangitis due to common bile duct stones.

PMID- 12802659
TI  - Resection of presacral ganglioneurofibroma by laparoscopy.
AB  - BACKGROUND: Tumors of the retrorectal space are rare. They comprise a
      heterogeneous group of benign or malignant tumors that cause similar symptoms due
      to their location in presacral space. If possible, complete surgery excision is
      the therapy of choice mainly through a sacral, abdominal-sacral, or a pure
      abdominal or perineal axis. CASE REPORT: A 15-year-old asymptomatic patient was
      diagnosed with a retrouterine tumor during her first gynecological examination.
      Magnetic resonance imaging of the pelvis showed a 10 x 8.5 x 7-cm encapsulated
      presacral tumor. Retrorectal ganglioneurofibroma was removed by laparoscopy with
      preservation of the sympathetic and parasympathetic nerves and the sacral roots
      of the ischiadic nerves. No sensory or motoric dysfunction of the legs, bladder,
      or rectum was observed postoperatively. CONCLUSION: This is the first case report
      of a complete endoscopic removal of large presacral ganglioneurofibroma in an
      asymptomatic woman.

PMID- 12802660
TI  - Laparoscopic treatment of pancreatic insulinoma.
AB  - Laparoscopy and laparoscopic ultrasonography (LUS) have been proposed for the
      diagnosis and treatment of pancreatic insulinoma. We present for cases of
      pancreatic insulinoma approached by laparoscopy guided by LUS. In three cases,
      insulinomas were in the pancreatic body and in one case in the pancreatic head.
      All lesions were detected preoperatively by abdominal US and confirmed by
      computed tomography. Laparoscopy was performed under general anesthesia. LUS was
      performed using a 10-mm flexible probe. In two cases the adenoma was enucleated
      using scissors and electrocoagulation, major vessels were controlled using clips,
      and enucleation was completed using a 30-mm endo-GIA. In one case a laparoscopic
      distal pancreatectomy with spleen preservation was performed. In one case the
      adenoma was deep in the pancreatic head; minilaparotomy was performed and the
      adenoma enucleated. Patients were discharged in good health 5-7 days after
      surgery. The postoperative course was complicated in one case of enucleation by
      peripancreatic fluid collection that was treated percutaneously. Our experience
      confirms that accurate localization followed by excision of tumors via the
      laparoscopic approach constitute a significant advance in the management of
      insulinoma.

PMID- 12802661
TI  - Laparoscopic extraperitoneal excision of a nerve sheath tumor of the spermatic
      cord.
AB  - A 60-year-old male presented with a nontender irreducible mass in the right
      groin. Examination revealed swelling in the inguinal canal in the region of the
      deep inguinal ring. He underwent laparoscopic, extraperitoneal exploration of the
      spermatic cord, where a soft tissue tumor was identified and excised.
      Histological examination confirmed a nerve sheath tumor. Nerve sheath tumors are
      uncommon neoplasms of peripheral nerves, which theoretically can arise from any
      nerve fiber but have only been described in the spermatic cord in three reports
      in the literature. We are not aware of any reports describing their excision
      either laparoscopically or by the extraperitoneal route.

PMID- 12802662
TI  - Combined laparoscopic-assisted right hemicolectomy and low anterior resection for
      synchronous colorectal carcinomas.
AB  - BACKGROUND: Two cases of combined laparoscopic- assisted right hemicolectomy and
      low anterior resection for malignancy are presented to illustrate the technical
      aspects of performing two concurrent laparoscopic-assisted bowel resections with
      sequential anastomosis. Although there are similarities with laparoscopic
      assisted total proctocolectomy, the need for complete mesenteric dissection in
      two areas, removal of two separate specimens containing malignancy, and the need
      for two anastomoses raise unique technical considerations which include port
      placement, sequence of dissection, choice of specimen extraction sites, specimen
      handling, and sites for extracorporeal anastomosis. METHODS: Operative notes,
      operative videotapes, and hospital inpatient and outpatient records were reviewed
      for both patients. RESULTS: Laparoscopic-assisted combined resection was
      completed in both patients. In both cases, laparoscopic total mesorectal excision
      was performed. Maximum incision length was 6 cm. Both patients were ready for
      discharge on postoperative day 3. CONCLUSION: Combined laparoscopic assisted
      right colectomy and low anterior resection can be performed for synchronous
      colorectal malignancies with curative intent.

PMID- 12802663
TI  - A thoracoscopic view of the nerve of Kuntz.
AB  - The nerve of Kuntz and alternate neural pathways (ANPs) have long been considered
      crucial for upper limb sympathetic supply. However, at thoracoscopy, these
      structures are neither consistently identified nor searched for. This is probably
      reflective of the effectiveness of an isolated second thoracic ganglionectomy for
      upper limb sympathectomy. We present the case of a 19-year-old male who underwent
      a second thoracic ganglionectomy for palmar hyperhidrosis. On the left side,
      approximately 2.5 cm lateral to the typically located sympathetic chain, a
      filamentous structure (one-quarter the diameter of the sympathetic chain),
      identified as the nerve of Kuntz, was noted coursing across the neck of the
      second rib.

PMID- 12802664
TI  - PicSOr: an objective test of perceptual skill that predicts laparoscopic
      technical skill in three initial studies of laparoscopic performance.
AB  - BACKGROUND: Laparoscopic surgery requires surgeons to infer the shape of 3-D
      structures, such as the internal organs of patients, from 2-D displays on a video
      monitor. Recent evidence indicates that the issue is not resolved by the use of
      contemporary 3-D camera systems. It is therefore crucial to find ways of
      measuring differences in aptitude for recovering 3-D structure from 2-D images,
      and assessing its impact on performance. Our aim was to test empirically for a
      relationship between laparoscopic ability and the perceptual skill of recovering
      information about 3-D structures from 2-D monitor displays. METHODS: Participants
      in three studies completed a simulated laparoscopic cutting task as well as the
      Pictorial Surface Orientation (PicSOr)3 Test. In studies 1 (n = 48) and 2 (n =
      32) both groups were laparoscopic novices, and in study 3 (n = 34) 18 of the
      participants were experienced laparoscopic surgeons. FINDINGS: All three studies
      showed that PicSOr consistently predicted the laparoscopic performance of
      participants on the laparoscopic cutting task (study 1, r = 0.5, p < 0.0003;
      study 2, r = 0.5, p < 0.004; and study 3, r = 0.42, p = 0.017). Furthermore, it
      was also a significant predictor of laparoscopic surgeons' performance (r = 0.54,
      p = 0.047). INTERPRETATIONS: This is the first objective perceptual psychometric
      test to reliably predict laparoscopic technical skills. PicSOr provides a tool
      for assessing which trainees have the potential to learn minimal access surgery.

PMID- 12802665
TI  - Laparoscopic cholecystectomy under spinal anesthesia with nitrous oxide
      pneumoperitoneum: a feasibility study.
AB  - BACKGROUND: Spinal anesthesia has been successfully used to perform various
      laparoscopic procedures. However, laparoscopic cholecystectomy under spinal
      anesthesia has not been reported. Is this feasible? METHODS: Ten successive
      laparoscopic cholecystectomies were performed under spinal anesthesia. The
      surgical technique was modified using nitrous oxide insufflation, lower levels of
      intraabdominal pressure, modified trocar sites, and minimal surgical
      manipulation. We used spinal anesthesia by intrathecal hyperbaric 10-12 mg
      bupivacaine with 10 microg fentanyl to give an anesthetic level at T8-T6.
      RESULTS: The mean age was 39.3 years and there were four females. Only one
      patient was converted to general anesthesia due to intolerable shoulder pain. One
      patient vomited intraoperatively. Nine patients considered the procedure well
      tolerated under spinal anesthesia. The mean operative time was 47.4 min.
      Postoperatively, there were minimal pain and no vomiting. CONCLUSIONS:
      Laparoscopic cholecystectomy can be performed successfully under spinal
      anesthesia and is well tolerated.

PMID- 12802666
TI  - Laparoscopic gastric banding.
AB  - INTRODUCTION: Laparoscopic gastric banding (LGB) is currently the most popular
      purely restrictive bariatric operation in Europe and many other countries. It has
      a low operative morbidity, but is associated with a substantial late complication
      rate. Many late complications have been attributed to technical errors or to the
      learning curve. The aim of this paper is to present our results with gastric
      banding after the learning curve in order to disclose the true incidence of long
      term complications. METHODS: LGB was introduced in our department in December
      1995. Thirty patients were operated on until June 1997 using the early banding
      technique (band within the lesser sac), at which time the surgical technique was
      slightly modified in order to place the band above the lesser sac. Then another
      300 patients underwent LGB using either the Lapband or the SAGB system. This
      report focuses on the latter patients. All the data were collected prospectively.
      RESULTS: The series includes 300 patients (257 women and 43 men) with a mean age
      of 38.3 years (19-64). The mean initial weight was 119.2 kg (57-179), initial
      body mass index (BMI) was 43.3 kg/m2 (21-64), and initial excess weight was 96.5%
      (0-191). The mean duration of surgery was 90 min, decreasing over time to a mean
      of 75 min for the last 50 cases. Early overall morbidity was 6.6%. Major
      complications occurred in 7 patients (2.3%). Excess weight loss (EWL) was at
      least 50% in 66% of the patients after 2 years, averaging 60%, with no
      substantial change until 4 years, and the BMI stabilized between 30 and 31 kg/m2.
      Forty-nine patients developed a total of 52 long-term complications, of which 23
      (7.6%) were related only to the port or catheter. Band erosion occurred in 17
      (5.6%), pouch dilatation with slippage in 8 (2.6%), and infection in 4 (1.3%)
      patients. Fifty-five reoperations were necessary. Twenty-five of these were
      related only to the port. The band was removed from 26 (9%) patients, of whom 17
      were converted to Roux-en-Y gastric bypass. CONCLUSIONS: LGB gives satisfactory
      results in terms of weight loss in about two-thirds of the patients. Even beyond
      the learning curve, the long-term morbidity is not negligible, but is acceptable
      compared to other procedures such as vertical banded gastroplasty. Conversion to
      gastric bypass is possible when complications occur and can be performed when the
      band is removed in most cases.

PMID- 12802667
TI  - Comparison of adhesion formation associated with Pro-Tack (US Surgical) versus a
      new mesh fixation device, Salute (ONUX Medical).
AB  - BACKGROUND: We evaluated efficacy and associated adhesion formation of an
      innovative mesh fixation device versus the helical tack device and analyzed two
      implantation techniques. METHODS: Six purpose-bred female hounds were evaluated
      in this 90-day survival study. Six 4-cm round patches of 1-mm thick DualMesh were
      fixed to the abdominal wall with either 10 Pro-Tack or 10 Salute constructs in
      each patch. Zero to 4 additional patches were implanted with only Salute
      constructs. RESULTS: Adhesion severity scores were significantly higher for
      middle left abdominal wall sites versus lower right and upper left sites. The
      adhesion dissection score was higher for group T (Pro-Tack) versus group S
      (Salute). CONCLUSION: No significant effects occurred with adhesion extent
      scores, but group T developed denser adhesions. The second analysis determined
      that no significant differences existed relevant to secondary Salute placement,
      although the total score approached significance (p < 0.09). Salute equipment was
      easier to handle and allowed repositioning of the patch during operation.

PMID- 12802668
TI  - Multimodality treatments with endoscopic mucosal resection of esophageal squamous
      cell carcinoma with submucosal invasion.
AB  - BACKGROUND AND STUDY AIMS: A standard treatment for esophageal squamous cell
      carcinoma (SCC) with submucosal invasion is considered to be radical resection at
      present. In this study, we evaluated the efficacy of multimodality treatments
      with endoscopic mucosal resection (EMR) of esophageal SCC with submucosal
      invasion. METHOD: Eighteen cases of SCC with submucosal invasion were treated
      with EMR. Lymphatic invasion was found in 11 cases (67%), and there were no cases
      of blood vessel invasion. EMR was performed prior to any other treatment.
      Chemotherapy and/or radiotherapy were added if indicated by the histopathological
      features. RESULTS: There were no cases of local recurrence. Lymph-node recurrence
      was detected in 1 case treated with EMR alone. There were no cases of cancer
      death. The overall survival rate was 83% in all patients. CONCLUSIONS:
      Multimodality treatments with EMR were effective in treating esophageal SCC with
      submucosal invasion.

PMID- 12802669
TI  - Long-term results of major bile duct injury associated with laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Major bile duct injury (MBDI) is the most serious complication
      associated with laparoscopic cholecystectomy (LC). This study reports on long
      term outcomes and clinical factors which predicted the outcome of 25 patients
      with LC-associated MBDI. METHODS: Twenty-five consecutive patients receiving
      either primary (n = 11) or redo (n = 14) biliary reconstructive surgery at Cathay
      General Hospital for LC-associated MBDI were prospectively followed for 2 to 10
      (mean, 4.5) years to assess their long-term outcomes. Twelve clinical factors
      relevant to their outcomes were analyzed. RESULTS: There was no mortality.
      Although the 1-year postoperative results were successful in 23 patients (92%),
      the mid- to long-term outcomes were successful in only 17 patients (68%). Eight
      patients (32%) developed biliary strictures at an average of 3.3 years
      postoperatively and required subsequent reoperation or biliary stenting.
      Statistical comparison of 12 risk factors between the successful and unsuccessful
      groups revealed that two were significant, namely, repair performed by a
      nonreferral surgeon (p = 0.02) and repair at a stage with recent active
      inflammation (p = 0.04). A serum alkaline phosphatase level greater than 400 IU
      in the sixth postoperative month was highly correlated with long-term nonsuccess
      (p = 0.01). CONCLUSIONS: Only 68% of patients with LC-associated MBDI who
      underwent reconstructive surgery at our institution had long-term success. A
      serum alkaline phosphatase level above 400 IU in the sixth postoperative month
      was predictive of nonsuccess. For better long-term results, repair should be
      performed by the referral surgeon at a stage without coexisting active
      inflammation.

PMID- 12802670
TI  - Extirpation of mass-screened adrenal neuroblastomas by retroperitoneoscopy.
AB  - BACKGROUND: A mass-screened neuroblastoma (MSN) shows low-grade malignancy.
      Although the tumor is small, open laparotomy requires a large incision. PURPOSE:
      Extirpation by retroperitoneoscopy (ER) was performed in children with MSN to
      reduce the surgical stress. METHODS: The indications for ER were (1) MSN
      originating from the adrenal gland and (2) a tumor size of less than 4 cm.
      Between January 2000 and June 2002, 6 children (mean age: 8.5 +/- 0.6 months)
      underwent ER. RESULTS: All children successfully underwent ER and no conversion
      of laparoscopy to open surgery was required. The only complication in one patient
      was a peritoneal tear. Oral intake was possible in all children the day after the
      operation. No port site metastasis or local recurrence was observed during follow
      up (15 to 29 months). CONCLUSIONS: Adrenal MSN less than 4 cm were successfully
      extirpated by ER. This method has the advantage of allowing patients an early
      return to eating and has no risk of postoperative ileus. ER is an available
      surgical technique for children with MSN less than 4 cm.

PMID- 12802671
TI  - Herbivore host plant selection: whitefly learns to avoid host plants that harbour
      predators of her offspring.
AB  - Evidence is accumulating that herbivorous arthropods do not simply select host
      plants based on their quality, but also on the predation risk associated with
      different host plants. It has been suggested that herbivores exclude plant
      species with high predation risk from their host range. This assumes a constant,
      predictable predation risk as well as a rather static behaviour on the part of
      the herbivore; plants are ignored irrespective of the actual predation risk. We
      show that adult females of a small herbivore, the whitefly Bemisia tabaci, can
      learn to avoid plants with predatory mites that attack only juvenile whiteflies,
      while they accept host plants of the same species without predators. Predatory
      mites disperse more slowly than whiteflies; they cannot fly and walk from plant
      to plant. Hence, by avoiding plants with predators, the whiteflies create a
      temporary refuge for their offspring. We suggest that the experience of arthropod
      herbivores with risks associated with host plants plays an important role in
      their host plant selection.

PMID- 12802672
TI  - Hot rocks or no hot rocks: overnight retreat availability and selection by a
      diurnal lizard.
AB  - I used radio telemetry to determine the effects of substrate size and composition
      on overnight retreat site selection by western fence lizards (Sceloporus
      occidentalis). In watersheds of northern California (USA), these lizards occupy
      two habitat types differing in substrate characteristics: rocky cobble bars found
      in the dry, active channels of rivers and grassy upland meadows. Rocky
      substrates, found almost exclusively on cobble bars, provided warmer potential
      retreat sites than all available retreat sites on meadows during the first 5 h of
      inactivity. Only cobble and sand substrates provided retreats with temperatures
      within the preferred daily active range (32-36 degrees C) during the inactive
      period for these lizards (1900-0900 hours). Females on a cobble bar used rocks as
      retreats on >90% of nights during the breeding season whereas females on a meadow
      used wood (>70% of nights) and burrows (>25% of nights). In contrast to females,
      cobble bar males used rocks significantly less frequently (<70%) and slept in the
      open air significantly more frequently (25% vs. <1%). Cobble bar females further,
      showed a significant preference for cobbles 15 cm thick, whereas the rocks used
      by males did not differ significantly in thickness from those measured in
      randomly placed transects. Rocks 15 cm thick were the warmest retreats commonly
      available on this habitat type. Thus, thermal microenvironments available to and
      chosen by gravid female lizards differ considerably between river and non-river
      habitats.

PMID- 12802673
TI  - Trophic partitioning in tropical rain forest birds: insights from stable isotope
      analysis.
AB  - Bird communities reach their highest taxonomic and trophic diversity in tropical
      rain forest, but the use of different foraging strategies to meet food
      requirements in such competitive environments is poorly understood. Conventional
      dietary analyses are poorly suited to investigate dietary patterns in complex
      systems. We used stable carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) isotope
      analysis of whole blood to examine avian trophic patterns and sources of diet in
      the tropical rain forest of Los Tuxtlas, Veracruz, Mexico. We used stable
      nitrogen isotope analysis to delineate trophic levels, and stable carbon isotope
      analysis to distinguish the relative contribution of C-3 and CAM/C-4 ultimate
      sources of proteins to diets. There was large inter- and intraspecific variation
      in whole blood delta(13)C and delta(15)N values in 23 species of birds. Stable
      nitrogen isotope analysis separated birds into several trophic levels, including
      species that obtained their dietary protein mostly from plants, insects or a
      combination of both food sources. Stable carbon isotope analysis showed that most
      birds fed on C3-based foods but Stub-tailed Spadebills (Platyrinchus cancrominus)
      included C-3- and C-4/CAM-specialist individuals. Our analyses provided insights
      into the nutritional contribution of plant and animal sources of protein and
      distinguish their photosynthetic origin over relatively long average time
      periods.

PMID- 12802674
TI  - Top-down and bottom-up processes in grassland and forested streams.
AB  - The influence of predatory fish on the structure of stream food webs may be
      altered by the presence of forest canopy cover, and consequent differences in
      allochthonous inputs and primary production. Eight sites containing introduced
      brown trout ( Salmo trutta) and eight sites that did not were sampled in the Cass
      region, South Island, New Zealand. For each predator category, half the sites
      were located in southern beech (Nothofagus) forest patches (range of canopy
      cover, 65-90%) and the other half were in tussock grassland. Food resources used
      by two dominant herbivores-detritivores were assessed using stable isotopes.
      (13)C/(12)C ratios were obtained for coarse particulate organic matter (CPOM),
      fine particulate organic matter (FPOM), algal dominated biofilm from rocks, and
      larvae of Deleatidium (Ephemeroptera) and Olinga (Trichoptera). Total abundance
      and biomass of macroinvertebrates did not differ between streams with and without
      trout, but were significantly higher at grassland sites than forested sites.
      However, taxon richness and species composition differed substantially between
      trout and no-trout sites, irrespective of whether streams were located in forest
      or not. Trout streams typically contained more taxa, had low biomass of predatory
      invertebrates and large shredders, but a high proportion of consumers with cases
      or shells. The standing stock of CPOM was higher at forested sites, but there was
      less FPOM and more algae at sites with trout, regardless of the presence or
      absence of forest cover. The stable carbon isotope range for biofilm on rocks was
      broad and encompassed the narrow CPOM and FPOM ranges. At trout sites, carbon
      isotope ratios of Deleatidium, the most abundant invertebrate primary consumer,
      were closely related to biofilm values, but no relationship was found at no-trout
      sites where algal biomass was much lower. These results support a role for both
      bottom-up and top-down processes in controlling the structure of the stream
      communities studied, but indicate that predatory fish and forest cover had
      largely independent effects.

PMID- 12802675
TI  - Recovery of a northern New England salt marsh plant community from winter icing.
AB  - High latitude salt marsh plant communities are frequently exposed to conspicuous
      winter ice disturbances, which trigger secondary succession. In this paper, we
      document the recovery of a northern New England salt marsh from a severe winter
      icing event in 1998. Ice disturbances that killed plants but that left the
      underlying peat intact recovered rapidly. However, ice damage that killed plants
      and removed the underlying peat, led to areas of physiologically harsh edaphic
      conditions, specifically waterlogged and anoxic soils that limited plant
      recolonization. A transplant experiment revealed that only the most stress
      tolerant plants were capable of invading the most stressful portions of ice
      disturbances. A second experiment that artificially dried disturbance patches
      accelerated patch recovery. These data suggest that recovery from intense ice
      disturbance is dependent on stress-tolerant plants invading edaphically harsh
      disturbances, eventually facilitating the recolonization of the community. This
      process likely takes longer than a decade for full recovery to occur in the areas
      where both plants and the peat base are removed.

PMID- 12802676
TI  - Reproductive energy investment in corals: scaling with module size.
AB  - In colonial modular organisms, differences in module size and colony growth
      patterns among species have the potential to impose varying constraints on
      reproductive investment. Here, we compare reproductive output among seven
      morphologically different species of spawning reef corals, and analyse the
      relationship between reproductive output and module (polyp) size. Reproductive
      output ranged between 132 and 384 J cm(-2), with lipid constituting the key
      indicator of energy investment. Lipid decreased by 85-100%, whereas protein and
      carbohydrate were relatively invariant between pre- and post-spawning tissues in
      all species, representing 1-15% and <1%, respectively, of the energy investment
      to reproductive output. The ratio of energy content in reproductive to somatic
      tissues (gonadosomatic index, GSI) varied among species from 0.20 (Symphyllia
      recta) to 1.31 (Acropora tenuis), the latter being the highest value reported for
      any iteroparous marine invertebrate. Surprisingly, small-polyped species
      (Acropora, Montipora) had 2- to 6-fold higher GSIs than large-polyped ones
      (Lobophyllia, Symphyllia). Energy equivalents of tissues increased with the 1.50
      1.76 power of polyp diameter for somatic tissues and with the 1.42-1.80 power of
      polyp diameter for reproductive output. In both cases, increases in energy
      equivalents with polyp diameter were less than the scaling exponent of 3
      predicted for an isometric relationship between tissue volume (or mass) and polyp
      diameter, indicating significant constraints of space, design or physiological
      energetics with increasing polyp size. We hypothesise that such constraints have
      played a key role in the evolution of modularity in cnidarians.

PMID- 12802677
TI  - Legume presence increases photosynthesis and N concentrations of co-occurring non
      fixers but does not modulate their responsiveness to carbon dioxide enrichment.
AB  - Legumes, with the ability to fix atmospheric nitrogen (N), may help alleviate the
      N limitations thought to constrain plant community response to elevated
      concentrations of atmospheric carbon dioxide (CO(2)). To address this issue we
      assessed: (1) the effects of the presence of the perennial grassland N(2 )fixer,
      Lupinus perennis, on biomass accumulation and plant N concentrations of nine
      species plots of differing plant composition; (2) leaf-level physiology of co
      occurring non-fixing species (Achillea millefolium, Agropyron repens, Koeleria
      cristata) in these assemblages with and without Lupinus; (3) the effects of
      elevated CO(2) on Lupinus growth and symbiotic N(2) fixation in both monoculture
      and the nine-species assemblages; and (4) whether assemblages containing Lupinus
      exhibit larger physiological and growth responses to elevated CO(2 )than those
      without. This study was part of a long-term grassland field experiment (BioCON)
      that controls atmospheric CO(2) at current ambient and elevated (560 micromol
      mol(-1)) concentrations using free-air CO(2) enrichment. Nine-species plots with
      Lupinus had 32% higher whole plot plant N concentrations and 26% higher total
      plant N pools than those without Lupinus, based on both above and below ground
      measurements. Co-occurring non-fixer leaf N concentrations increased 22% and mass
      based net photosynthetic rates increased 41% in plots containing Lupinus compared
      to those without. With CO(2) enrichment, Lupinus monocultures accumulated 32%
      more biomass and increased the proportion of N derived from fixation from 44% to
      57%. In nine-species assemblages, Lupinus N derived from fixation increased
      similarly from 43% to 54%. Although Lupinus presence enhanced photosynthetic
      rates and leaf N concentrations of co-occurring non-fixers, and increased overall
      plant N pools, Lupinus presence did not facilitate stronger photosynthetic
      responses of non-fixing species or larger growth responses of overall plant
      communities to elevated CO(2). Non-fixer leaf N concentrations declined similarly
      in response to elevated CO(2) with and without Lupinus present and the
      relationship between net photosynthesis and leaf N was not affected by Lupinus
      presence. Regardless of the presence or absence of Lupinus, CO(2) enrichment
      resulted in reduced leaf N concentrations and rates of net photosynthesis.

PMID- 12802678
TI  - Sources of variation in consumer-diet delta 15N enrichment: a meta-analysis.
AB  - Measurements of delta15N of consumers are usually higher than those of their
      diet. This general pattern is widely used to make inferences about trophic
      relationships in ecological studies, although the underlying mechanisms causing
      the pattern are poorly understood. However, there can be substantial variation in
      consumer-diet delta15N enrichment within this general pattern. We conducted an
      extensive literature review, which yielded 134 estimates from controlled studies
      of consumer-diet delta15N enrichment, to test the significance of several
      potential sources of variation by means of meta-analyses. We found patterns
      related to processes of nitrogen assimilation and excretion. There was a
      significant effect of the main biochemical form of nitrogenous waste: ammonotelic
      organisms show lower delta15N enrichment than ureotelic or uricotelic organisms.
      There were no significant differences between animals feeding on plant food,
      animal food, or manufactured mixtures, but detritivores yielded significantly
      lower estimates of enrichment. delta15N enrichment was found to increase
      significantly with the C:N ratio of the diet, suggesting that a nitrogen-poor
      diet can have an effect similar to that already documented for fasting organisms.
      There were also differences among taxonomic classes: molluscs and crustaceans
      generally yielded lower delta15N enrichment. The lower delta 15N enrichment might
      be related to the fact that molluscs and crustaceans excrete mainly ammonia, or
      to the fact that many were detritivores. Organisms inhabiting marine environments
      yielded significantly lower estimates of delta15N enrichment than organisms
      inhabiting terrestrial or freshwater environments, a pattern that was influenced
      by the number of marine, ammonotelic, crustaceans and molluscs. Overall, our
      analyses point to several important sources of variation in delta15N enrichment
      and suggest that the most important of them are the main biochemical form of
      nitrogen excretion and nutritional status. The variance of estimates of delta15N
      enrichment, as well as the fact that enrichment may be different in certain
      groups of organisms should be taken into account in statistical approaches for
      studying diet and trophic relationships.

PMID- 12802679
TI  - Increased variation in mtDNA in patients with familial sensorineural hearing
      impairment.
AB  - Analyses of mitochondrial DNA (mtDNA) sequences have revealed non-neutral
      patterns, suggesting that many amino acid mutations in animal mtDNA may be mildly
      deleterious, but this has not been verified in human clinical series. Since
      sensorineural hearing impairment (SNHI) is a common manifestation in many of the
      syndromes caused by mutations in mtDNA, this may be regarded as the phenotype of
      choice in attempts to detect mutations that may have a mildly deleterious effect
      on mitochondrial function. We selected 32 subjects from among 117 unrelated SNHI
      patients with SNHI in maternal relatives by means of family history, determined
      the entire coding region sequence of mtDNA and compared the sequence variation
      with that in 32 haplogroup-matched controls taken at random from 192 Finnish
      sequences. The 32 control sequences differed from the remaining 160 sequences by
      36+/-9 substitutions (mean +/- SD), while the difference for the 32 patients was
      58+/-4 substitutions ( P=0.005 for difference; Wilcoxon signed rank test).
      Differences were also found in the number of new haplotypes and new non
      synonymous mutations or mutations in tRNA or rRNA genes. A total of 12 rare mtDNA
      variants were detected in the patients, and only 3 of these were considered to be
      neutral in effect. It is proposed that increased sequence variation in mtDNA may
      be a genetic risk factor for SNHI, and the increased frequency of rare haplotypes
      in these patients points to the presence of mildly deleterious mutations in
      mtDNA.

PMID- 12802680
TI  - Lung cancer risk in germline p53 mutation carriers: association between an
      inherited cancer predisposition, cigarette smoking, and cancer risk.
AB  - We recently observed a significantly increased risk for lung cancer in carriers
      of p53 germline mutations. Because cigarette smoking is known to play an
      important role in increasing the risk for lung cancer in the general population,
      we wanted to determine the role of cigarette smoking in lung cancer risk in
      people with a genetic susceptibility based on a p53 germline mutation. We studied
      1263 people from 97 families enrolled in a cohort study of families
      systematically ascertained through childhood soft-tissue sarcoma patients treated
      at the M.D. Anderson Cancer Center, University of Texas, between 1944 and 1975.
      We assessed the incidence of lung and smoking-related cancers in 33 carriers of
      germline p53 mutations and in 1,230 noncarriers to determine whether there was an
      association between an inherited cancer predisposition, cigarette smoking, and
      cancer risk. We analyzed the association between cigarette smoking, mutation
      status, and lung and other smoking-related cancers by the Kaplan-Meier method and
      the Cox proportional hazards model with adjustments for birth year, race, and
      sex. In the hazards model, we incorporated a robust variance estimation to adjust
      for familial correlation. We observed an increased risk of a variety of
      histological types of lung cancer in the carriers of the p53 germline mutation.
      Mutation carriers who smoked had a 3.16-fold (95% confidence interval =1.48-6.78)
      higher risk for lung cancer than the mutation carriers who did not smoke. Our
      results demonstrate that cigarette smoking significantly increases lung cancer
      risk in carriers of a germline p53 mutation. This finding could be useful in
      designing strategies for early detection and treatment of lung and smoking
      related cancers in individuals with this inherited cancer predisposition.

PMID- 12802681
TI  - Differential expression of six novel peroxidase cDNAs from cell cultures of
      sweetpotato in response to stress.
AB  - Six peroxidase (POD) cDNAs were isolated from suspension cultures of sweetpotato
      (Ipomoea batatas) by cDNA library screening, and their expression was
      investigated with a view to understanding the physiological functions of each POD
      in relation to environmental stress. The gene products encoded by these cDNAs
      could be divided into two groups, anionic PODs (SWPA4, SWPA5, SWPA6) and basic
      PODs (SWPB1, SWPB2, SWPB3), on the basis of the predicted pI values of the mature
      proteins. RT-PCR analysis revealed that the six POD genes showed diverse
      expression patterns in various tissues of intact plants, a various stages of
      growth in suspension cultures, and in leaf tissues exposed to different stresses.
      The six genes from which they were derived are predominantly expressed in
      cultured cells of sweetpotato. Thus, transcripts of swpa4 were not detected in
      any tissues of the intact plant. The genes swpa6 and swpb1 were highly expressed
      in root tissues, whereas swpa6 and swpb3 were highly expressed in stem tissues.
      During suspension culture, the expression patterns of the six genes differed from
      each other. The level of swpa4, swpa5, swpb2 and swpb3 transcripts progressively
      increased during culture, whereas swpa6 and swpb1 showed high expression levels
      regardless of the age of the culture. In leaf tissues the six POD genes responded
      differently to various abiotic stresses. In particular, swpa4 was highly induced
      by several abiotic stresses, including exposure to hydrogen peroxide (440 mM) or
      NaCl (100 mM), and wounding of leaf tissues, suggesting that this POD gene is
      inducible by many stresses. Based on the different expression patterns of these
      POD genes, we propose that each POD may have different enzymatic properties and
      physiological functions during cell growth and development.

PMID- 12802682
TI  - Recombinant Duffy binding-like-alpha domains of Plasmodium falciparum erythrocyte
      membrane protein 1 elicit antibodies in rats that recognise conserved epitopes.
AB  - Plasmodium falciparum parasites remodel the surface of human erythrocytes on
      invasion by the insertion of parasite-derived proteins in knob-like protrusions.
      P. falciparum erythrocyte membrane protein 1 (PfEMP-1), a variant surface
      antigen, has been shown to be anchored in these knobs and mediates adhesion to
      various host endothelial receptors. These proteins also undergo clonal antigenic
      variation as a means of immune evasion. Duffy binding-like-alpha(DBL-alpha)
      domain together with the cysteine-rich interdomain region form the head structure
      of the PfEMP1 molecule. In this report, we used ten different recombinant DBL
      alpha fusion proteins expressed in Escherichia coli to generate antibodies in
      experimental animals. Five out of ten recombinant DBL-alpha fusion proteins were
      immunogenic and induced antibodies that reacted with conserved peptides derived
      from PfEMP1. Indirect immunofluorescence assay was used to localise PfEMP-1-DBL
      alpha expressed in parasitised erythrocytes. Positive fluorescence reactivity was
      observed within the cytoplasm and with membrane structures but not on the surface
      of intact P. falciparum-infected erythrocytes.

PMID- 12802683
TI  - Amplified fragment length polymorphism analyses of Eimeria spp.: an improved
      process for genetic studies of recombinant parasites.
AB  - Application of the amplified fragment length polymorphism (AFLP) technique to
      genetic mapping studies requires high quality DNA as a template. In the case of
      Eimeria spp., this has previously been in the form of chromosomal DNA obtained
      from purified sporozoites recovered from large numbers of oocysts (generally up
      to 2 x 10(8)). In order for the AFLP technique to be more easily applied to
      studies on the genetics of Eimeria maxima, for which only smaller numbers of
      oocysts are available, a simplified, more efficient method for the recovery of
      genomic DNA from small numbers of oocysts was developed. Our new method should
      also be useful for genetic analyses of other coccidial parasites and for the
      recovery of AFLP-quality DNA from other pathogens.

PMID- 12802684
TI  - Haematuria, transient proteinuria, serpiginous-border skin rash, and cardiomegaly
      in a 10-year-old girl. Diagnosis: Acute post-streptococcal glomerulonephritis
      associated with acute rheumatic pericarditis.

PMID- 12802685
TI  - The growing skull fracture, a rare complication of paediatric head injury.

PMID- 12802686
TI  - Liver failure in a neonate with congenital adrenal hyporesponsiveness.

PMID- 12802687
TI  - Cow milk allergy presenting as colitis.

PMID- 12802688
TI  - Accidental hypothermia in an infant with Prader-Willi syndrome.

PMID- 12802689
TI  - Placentation in the alpaca Lama pacos.
AB  - Reproduction in South American camelids is poorly studied. To extend our
      knowledge of the development and cellular physiology of the placenta in the
      alpaca Lama pacos, we have examined specimens from day 150 of pregnancy to term.
      Morphological investigations using light, transmission and scanning electron
      microscopy, the histochemical localization of iron, alkaline and acid phosphatase
      activity, and the immunodetection of placental lactogen hormone were performed.
      Throughout pregnancy there was a progressive increase in the depths of folds on
      the uterine mucosa surface together with a thickening of the endometrium.
      Glandular cells exhibited PAS and acid phosphatase (AcP) positive secretion
      granules. In the chorion, giant trophoblast polyploid cells gradually became more
      numerous and larger. Non-giant cells exhibited positive granules for PAS,
      alkaline phosphatase (AkP) reaction and immunostaining for bovine placental
      lactogen hormone (PLH). SDS -PAGE electrophoresis and Western blotting procedures
      also confirmed the presence of a bovine PLH-like glycoprotein in the fetal alpaca
      placenta. Over the glandular openings, the chorion formed typical areolae, where
      the trophoblast exhibited AcP and PAS positive reactions. At these sites, the
      fetal endothelial cells contained iron-storage granules in their cytoplasm. The
      trophoblast-epithelial interface exhibited a complex microvillous
      interdigitation, in which an AkP reaction was very prominent. The chorionic
      capillaries progressively indented adjacent trophoblast cells. These data suggest
      that although the epitheliochorial alpaca placenta is diffuse, various
      trophoblast cell types and specialized areas of the maternofetal interface give
      the placenta micro-regional functions where histiotrophic nutrition, hormone
      production and molecular exchange are prevalent.

PMID- 12802690
TI  - Lectin histochemistry of the lymphoid organs of the chicken.
AB  - Cellular interactions within the immune system are in part mediated via the
      carbohydrate-rich coat of the cell membrane, the glycocalyx, of which the
      terminal carbohydrate residues are of particular functional importance. Thus,
      these carbohydrate residues from thymus, bursa of Fabricius, spleen and bone
      marrow of 2- and 30-day-old chickens were investigated by lectin histochemistry.
      In the thymus, mannose as well as N-acetyl-glucosamine (glcNAc)-specific lectins
      labelled macrophages, epithelial reticulum cells and lymphocytes within the
      cortex. In the bursa of Fabricius, the brush border of the lining epithelium, the
      macrophages and the endothelium were labelled by mannose-specific lectins. The
      follicle-associated epithelium was labelled by a broad spectrum of lectins.
      Epithelial cells that separated the cortex from the medulla and large mononuclear
      cells in the cortex were only being labelled by N-acetyl-galactosamine (galNAc)
      specific and glcNAc-specific lectins, respectively. In the spleen, lymphocytes of
      the peri-ellipsoid lymphocyte sheaths and macrophages of the red pulp were
      labelled by lectins of nearly all sugar specificities. In general, glycotopes of
      these organs were more intensively labelled in the 2-day-old chicken than in the
      30-day-old chicken, indicating changes in glycotope expression during post
      hatching development. Thus, cells of the avian immune system are as rich and
      diverse in their lectin binding sites as their mammalian counterparts, indicating
      that similar carbohydrate lectin interactions between cells and matrices take
      place in birds as well.

PMID- 12802691
TI  - Deviations from the diffusion tensor model as revealed by contour plot
      visualization using high angular resolution diffusion-weighted imaging (HARDI).
AB  - The standard diffusion tensor model is limited in its ability to provide detailed
      information about multidirectional fiber architecture in human white matter.
      Additional directional acquisition of diffusivity properties with high angular
      resolution diffusion-weighted imaging (HARDI) acquisition schemes may deliver
      more information on areas with fiber crossings than standard DTI. However,
      representation of the additional information and the rating and visualization of
      fiber complexity is challenging. We used projection 2D-plots in combination with
      a HARDI acquisition scheme of 129 diffusion directions and compared the spherical
      diffusion variance index (SDI) with the relative anisotropy index (RAI). In
      normal controls, white matter areas with unidirectional fiber arrangement and
      areas with more complex fiber composition were identified with this approach.
      HARDI confirms and can visualize deviations from the tensor-like representation,
      thereby providing information on fiber structure complexity, which may be of
      considerable interest for clinical studies.

PMID- 12802693
TI  - Intraventricular administration of recombinant tissue plasminogen activator for
      intraventricular hemorrhage in the newborn.
AB  - Intraventricular hemorrhage remains associated with high mortality and morbidity.
      Its most serious complication is posthemorrhagic hydrocephalus caused by multiple
      small blood clots obstructing the arachnoid villi. We treated three newborn
      infants (one term, two preterm) with posthemorrhagic hydrocephalus using
      recombinant tissue plasminogen activator, a thrombolytic agent, injected into the
      ventricles with a spinal needle. Sufficient fibrinolysis was achieved in these
      preterm patients. They all survived, and shunt surgery was only required in one.
      No adverse reactions or side effects have occurred. Intraventricular fibrinolysis
      with tissue plasminogen activator seems to be safe and effective for the
      treatment of intraventricular hemorrhage. However, controlled studies are needed
      for assessing treatment efficiency.

PMID- 12802697
TI  - Growth hormone secretagogues: past, present and future.
AB  - Growth hormone-releasing peptides (GHRPs) or growth hormone secretagogues (GHSs)
      of peptide or non-peptide structure are able to stimulate growth hormone
      secretion. They act through a growth hormone-releasing hormone
      (GHRH)/somatotropin release inhibiting factor (SRIF) independent pathway. A
      receptor able to bind to these compounds was cloned in 1996, and a natural ligand
      of this receptor, named ghrelin, was characterized in 1999. The potential
      therapeutic value of such compounds is considerable as they offer an alternative
      therapy for treatment of deficiency in growth hormone secretion. As growth
      hormone (GH) also participates in many anabolic effects, interest in these
      compounds is increasing and many clinical applications are expected in the
      future.

PMID- 12802695
TI  - Recurrent hemorrhage after initially complete occlusion of intracranial
      aneurysms.
AB  - Recurrent hemorrhage in the case of incompletely treated aneurysms is well known.
      The authors present a series of patients in whom rebleeding occurred in spite of
      totally occluded aneurysms. During a period of 12 years, 1170 patients with
      intracranial aneurysms were treated using either clipping (n=727) or coiling
      (n=443). In 11 of them, intracranial rebleeding occurred, in seven of whom
      routine post-treatment angiography revealed total aneurysm occlusion before the
      appearance of rehemorrhage. Further analysis focused on these seven patients.
      Their recurrent aneurysm ruptures happened with a mean latency of 9.5 months
      (range 21 h-48 months) from initial treatment. All aneurysms belonged to the
      anterior circulation. Three patients underwent primary clipping, and four
      experienced coiling first. The intracranial hemorrhages appeared mainly as
      intracerebral hematomas. The angiographically documented recurrent aneurysm
      configurations were caused by clip slippage (n=2), coil compaction (n=3), or coil
      migration/dislocation (n=1). In one case with primary surgery, clip slippage was
      possible but not confirmed by intraoperative view, because the patient died
      before therapeutic intervention. Two patients did not undergo therapy because of
      their poor clinical condition and died. Four of the remaining patients underwent
      clipping of the recurrent lesions, and one had recoiling. Final outcome was
      excellent/good in only two patients. The mainly poor outcome after rebleeding was
      caused by the high incidence of intracerebral hemorrhage.

PMID- 12802698
TI  - Non-HIV antivirals - a review of the recent patent literature.
AB  - This review covers the non-HIV antiviral patent literature from December 2001 to
      April 2002. Most of the patent applications describe new compounds for the
      treatment of hepatitis C virus (HCV) by inhibition of the NS3 serine protease.
      Several examples of both nucleoside and non-nucleoside inhibitors of the HCV
      polymerase NS5B have been reported. Hepatitis B virus (HBV) therapy continues to
      be dominated by nucleoside analogs, but several non-nucleoside HBV polymerase
      inhibitors have also been reported. In addition, a number of patents describing
      non-nucleoside inhibitors of the human cytomegalovirus (HCMV), the herpes simplex
      virus (HSV-1 and HSV-2) and the varicella zoster virus (VZV) DNA polymerase are
      also reviewed. A number of patents that appeared in 2002 hold promise for the
      treatment of respiratory syncytial virus (RSV) with small molecule inhibitors.
      Various approaches to the treatment of hepatitis D virus (HDV), picornaviruses
      and the human papilloma virus (HPV) are also described.

PMID- 12802699
TI  - Bortezomib (millennium pharmaceuticals).
AB  - Bortezomib is a ubiquitin proteasome inhibitor under development by Millennium
      Pharmaceuticals (formerly LeukoSite Inc) for the potential treatment of various
      solid tumors [312219], [392555]. In the first quarter of 2001, Millennium
      initiated two phase II trials evaluating bortezomib for multiple myeloma (MM). A
      phase II trial in patients with chronic lymphocytic leukemia (CLL) was initiated
      in June 2001 [400636], [412848]. By November 2001, the agent was in a number of
      phase I trials and combination studies for various solid tumors, including
      prostate, pancreatic and colorectal carcinoma [412700], [429923], [435062],
      [452675]. In June 2002, bortezomib was awarded Fast Track status by the FDA
      [453557], and in the same month pivotal phase III trials evaluating bortezomib in
      MM were initiated in the US, Canada and Europe [454446].

PMID- 12802700
TI  - Naltrexone depot (DrugAbuse Sciences).
AB  - DrugAbuse Sciences is developing naltrexone depot, a sustained-release (SR)
      injectable formulation of naltrexone for the potential treatment of alcoholism
      and opiate addiction. This formulation was developed to help alcoholics and
      heroin addicts overcome the problems with compliance experienced with the daily
      administered tablet form of naltrexone [322165]. Phase III trials of naltrexone
      depot for the treatment of alcoholics and phase II trials of naltrexone depot for
      injectable suspension (Naltrel) for the treatment of opiate addiction are ongoing
      [426301].

PMID- 12802701
TI  - Tryptase inhibitors - review of the recent patent literature.
AB  - The past several years has seen research increasingly focused around the
      inhibition of tryptase, a mast cell protease implicated in a myriad of pro
      inflammatory responses. Although few compounds have reached the clinic, several
      monobasic and multibasic small molecules have emerged as promising candidates as
      a treatment for asthma and other allergic and inflammatory disorders. This
      summary reviews recent patent activity of tryptase inhibitors and briefly
      outlines recent tryptase inhibitor literature and clinical updates.

PMID- 12802702
TI  - Gastrin and gastrin receptor ligands - a review of recent patent literature.
AB  - The peptide hormone gastrin is involved in the regulation of acid secretion in
      the stomach and acts as a growth hormone in the stomach. Although gastrin
      receptors are expressed in many tumors throughout the body, the clinical
      significance of this is still unknown. Despite considerable efforts from many
      pharmaceutical organizations for over a decade, there is as yet no commercially
      available gastrin ligand. This review covers the patent literature relating both
      to novel gastrin ligands and to new applications of gastrin and its ligands,
      including gastrin antibodies, between April 1998 and April 2002.

PMID- 12802703
TI  - Lucinactant (Discovery Laboratories).
AB  - Discovery Laboratories Inc (formerly Acute Therapeutics Inc (ATI) is developing
      lucinactant, originally identified at the Scripps Research Institute and
      sublicensed from Johnson & Johnson, for the potential treatment of respiratory
      diseases [174059], [357077], [361765], [422819]. The company anticipated filing
      an NDA for lucinactant in 2002, and by March 2002, lucinactant was in two pivotal
      phase III international trials for respiratory distress syndrome (RDS) in
      premature infants, a phase III trial for meconium aspiration syndrome (MAS) in
      full-term infants, and a phase II trial for acute lung injury/acute respiratory
      distress syndrome (ALI/ARDS) in adults. The company expected to complete trials
      by late 2003 [400846], [445166]. In February 2002, lucinactant was awarded Orphan
      Drug product designation in Europe for the treatment of ALI, which incorporates
      ARDS [440083]. By April 2001, Orphan Drug status in the US had been granted for
      lucinactant for MAS [301112], RDS and ARDS [404160]. The FDA also designated the
      drug a Fast Track product for the treatment of MAS [302120] and ARDS [301562],
      [302176], [404160].

PMID- 12802704
TI  - Nesiritide (Scios).
AB  - Nesiritide is a recombinant B-type (brain) natriuretic peptide developed by Scios
      for the potential treatment of congestive heart failure (CHF). In August 2001,
      the product was approved and launched in the US for the intravenous treatment of
      patients with acute decompensated congestive heart failure (ADCHF) who have
      dyspnea at rest or at minimal activity [418946], [420072]. By March 2002, Scios'
      European development partner, GlaxoSmithKline, expected to file a Marketing
      Authorization Application (MAA) for nesiritide in Europe in 2002 [446957].

PMID- 12802705
TI  - Calpains inhibitors--a review of the recent patent literature.
AB  - Calpain inhibitors prevent proteolytic degradation of cellular proteins due to
      activation of calcium-activated cysteine proteases (calpains). As a class, they
      show promising cytoprotective activity in a variety of disorders where the final
      common pathway is increased intracellular concentrations of calcium, activation
      of calpain-mediated protein degradation, and subsequent cell death. These
      disorders include cerebral stroke, cerebral and spinal cord trauma, and
      myocardial infarction.

PMID- 12802706
TI  - Dipeptidyl peptidase IV inhibitors.
AB  - The patent literature for dipeptidyl peptidase IV (DPP-IV) inhibitors for the
      period of January 2001 to May 2002 is reviewed. There has been increased interest
      in DPP-IV inhibitors since their potential for the treatment of diabetes was
      identified. This review will focus on reversible inhibitors of the enzyme, for
      which the primary interest has been for use in the treatment of Type II diabetes.
      The majority of the new chemical entities reported are dipeptide-like inhibitors
      that mimic the preferred substrates and the best of these display nanomolar
      activity. There have been fewer reports of non-peptide inhibitors suggesting that
      it is much more difficult to identify new classes of inhibitors. In addition to
      new chemical entities this review will cover new indications for DPP-IV
      inhibitors that have been identified using previously reported inhibitors as
      research tools.

PMID- 12802707
TI  - DX-890 (Dyax).
AB  - Dyax (formerly Protein Engineering Corp) and Debiopharm are developing DX-890, an
      inhibitor of human neutrophil elastase (HNE), for the potential treatment of
      pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary
      disease (COPD) [242806]. In December 1999, Debiopharm initiated phase I trials
      with an aerosol formulation of DX-890; studies were completed by October 2000
      [350718], [352554], [387155]. By August 2000, DX-890 was in phase II evaluation
      for the potential treatment of CF [378625], and in May 2002, Dyax planned to
      initiate a further study, in children with CF, within the year [451044]. By June
      2002, phase II trials in CF were ongoing in France and Spain, with results
      expected soon after this date [454485]. In September 2000, JP Morgan predicted a
      2005 launch for this drug, with estimated sales in that year of 23 US dollars
      million rising to 63 million US dollars in 2007 [397766].

PMID- 12802708
TI  - ONO-1714 (Ono).
AB  - Ono Pharmaceuticals is developing ONO-1714, a selective inducible NO synthase
      modulator, for the potential treatment of sepsis and hypotension. By March 1999,
      ONO-1714 had entered phase I trials [354023]. By June 2002, a phase II trial in
      hypotension during dialysis was ongoing in Japan and clinical pharmacology trials
      were underway in the UK [446138]. In August 1999, Lehmann Brothers gave ONO-1714
      a 10% probability of reaching the market with an expected launch in 2004. Sales
      were expected to peak at 50 million US dollars in 2012 [349228].

PMID- 12802709
TI  - Relationship between tumor necrosis factor-alpha genotype and success of emergent
      cerclage.
AB  - The guanine to adenine substitution at the -308 position in the tumor necrosis
      factor-alpha (TNF-alpha) gene promoter region results in a 5-fold greater
      cytokine response to an inciting event. We investigated whether this polymorphism
      is associated with cervical incompetence and adverse pregnancy outcome after
      emergent cerclage. Women with a diagnosis of cervical incompetence requiring an
      emergent cerclage between 15 and 24 weeks were enrolled. Women without pregnancy
      complications were recruited as controls. DNA extraction from peripheral blood
      and polymerase chain reaction (PCR) amplification of a 144-base pair segment of
      the TNF-alpha gene were performed with subsequent sequencing. Twenty-three women
      underwent emergent cerclage and participated in the study, 13 (57%) of whom
      delivered after 28 weeks. Twenty-three women served as controls. There were no
      differences in the TNF-alpha polymorphism between women with cervical
      incompetence and controls or between women with cervical incompetence who
      delivered before versus after 28 weeks. The TNF-alpha polymorphism was not
      associated with cervical incompetence or with delivery prior to 28 weeks in women
      who received an emergent cerclage.

PMID- 12802710
TI  - Location of accessory connection in infants presenting with supraventricular
      tachycardia in utero: clinical correlations.
AB  - The most common mechanism of fetal tachycardia is orthodromic reciprocating
      tachycardia utilizing an accessory atrioventricular connection, however, data
      regarding accessory connection location in patients with fetal tachycardia is
      limited. To investigate the location of accessory connections in fetal
      tachycardia, postnatal transesophageal electrophysiology studies were performed
      at one institution over a 10-year period in 24 infants with documented fetal
      tachycardia. The 18 infants with inducible orthodromic reciprocating tachycardia
      were grouped according to accessory connection location, and groups were compared
      regarding prenatal presentation and clinical course. Left-sided connections were
      found in 13 (72%) patients, while accessory connection location could not be
      determined in the remaining 5 (28%) patients. The presence of a left-sided
      accessory connection was associated with sustained tachycardia, depressed
      ventricular function, and the need for antiarrhythmic therapy in utero. No other
      difference in clinical or electrophysiologic data was found between groups. Our
      findings indicate that a high proportion of patients with fetal tachycardia have
      left-sided accessory connections, and a left-sided connection may adversely
      affect fetal hemodynamics and cardiac output.

PMID- 12802711
TI  - Congenital partial pericardial defect in a neonate: a case report.
AB  - This report describes a neonate with congenital partial absence of the
      pericardium associated with hypoplastic left heart syndrome. The patient
      presented with severe heart failure caused by a hypoplastic left ventricle. The
      infant died at 15 hours of age because of intractable congestive heart failure.
      Necropsy revealed, in addition to a hypoplastic left ventricle, a transverse
      biventricular constriction suggestive of partial absence of the pericardium. In
      addition to cardiovascular malformations, a left hydronephrosis and a bicornuate
      uterus was found. We report a rare clinical entity and review the literature.

PMID- 12802712
TI  - Staphylococcus aureus outbreaks among newborns: new frontiers in an old dilemma.
AB  - The acquisition of Staphylococcus aureus by the newborn in the early neonatal
      period is common. Most such acquisitions are not followed by infection, although
      the potential for serious infection increases in the intensive care unit setting.
      Attack rates for infection are quite variable, but outbreaks have occurred on
      many occasions. Although some bacterial virulence factors, such as exfoliative
      toxins, are associated with outbreaks, most epidemic strains do not have well
      defined virulence factors that can be incriminated. There are many possible
      control measures, but the implementation of these are balanced by the existing
      circumstances and perceived cost. As methicillin-resistant S. aureus (MRSA)
      becomes endemic in hospital settings, these bacteria are becoming much more
      common in nursery outbreaks. Over time, antibiotic selection and enhanced disease
      causation will lead to the evolution of hypervirulent MRSA clones. The latter
      will become an increasing problem unless effectively controlled.

PMID- 12802713
TI  - Expired nitric oxide in the newborn with high risk of perinatal infection.
AB  - The objective of this study is to determine expired nitric oxide (expNO) in the
      first 3 days of life in relation to: hours of life, gestational age, type of
      labor, and risk of perinatal infection. Our hypothesis has been that expNO
      increases in newborns with high risk of perinatal infection. Total expNO was
      measured in 166 newborns: 108 healthy (63 full-term and 45 preterm), 30 with low
      risk of perinatal infection, and 28 with high risk of perinatal infection treated
      with antibiotics but without positive hemoculture. Expired gas was collected
      using a face mask and NO concentration was determined by chemiluminescence. Total
      expNO neither correlated with gestational age, birth weight or serum NOx, nor
      changed after cesarean section, but was related to hours of life. Total expNO in
      the < or = 36-hour subgroups (median, interquartile range) was higher in the high
      risk perinatal infection newborns ( n = 8; 5.33 (4.5-7.2) nL/min*Kg) than in
      healthy newborns ( n = 59; 4.13 (3.5-4.7) nL/min*kg) or low-risk perinatal
      infection newborns ( n = 18; 3.99 (3.4-4.7) nL/min*kg). In the 37 to 72-hour
      subgroups there were also differences between healthy newborns ( n = 49; 4.68
      (4.1-5.3) nL/min*kg) or low-risk perinatal infection newborns on the one hand ( n
      = 12, 4.55 (3.9-5.2) nL/min*kg) and high risk perinatal infection newborns on the
      other ( n = 20; 9.69 (7.6-11.1) nL/min*kg). Then, total expNO increased in
      newborns with high risk of perinatal infection, regardless of hours of life.

PMID- 12802714
TI  - Congenital spine tuberculosis: early diagnosis by imaging studies.
AB  - Perinatal/congenital tuberculosis is a rare entity, even in human
      immunodeficiency virus (HIV) endemic populations, and is uniformly fatal if
      untreated. The liver and the lungs are the most commonly involved organs in this
      variety of tuberculosis and the spine is a rare site. We report the first case of
      spine tuberculosis with paravertebral abscess in a neonate who was only 3 weeks
      of age. The imaging studies, namely radiography, sonography, computed tomography
      (CT)-guided aspiration and magnetic resonance imaging (MRI), facilitated rapid
      diagnosis and early institution of chemotherapy. We highlight the role of imaging
      evaluation in the diagnostic armamentarium for tuberculosis of the newborn, as
      early diagnosis followed by appropriate treatment resulted in an excellent
      recovery in our patient.

PMID- 12802715
TI  - Neonatal invasive candidiasis: a prospective multicenter study of 118 cases.
AB  - A prospective multicenter study was conducted to assess the epidemiology of
      neonatal invasive candidiasis in Spain. In a total of 20,565 admissions to the 27
      participating neonatal units over an 18-month period, systemic candidiasis was
      diagnosed in 118 (0.57%) neonates. Candida species were isolated from the blood
      in 79 infants, from the urine in 33, and from the cerebrospinal fluid in 4; in 2
      cases, histologic evidence of deep tissue candidiasis was found at autopsy. Very
      low-birth-weight (VLBW) infants (< or = 1500 g) showed a significantly higher
      incidence of systemic candidiasis (4.8%) than infants weighing > 1500 g (0.2%) (
      p < 0.001). Candida albicans was the most frequent species (52.5%) followed by C.
      parapsilosis (23.7%), and C. tropicalis (7.6%). Only seven infants were treated
      with amphotericin B (initial dose 0.18 +/- 0.3 mg/kg, maximal daily dose 1.7 +/-
      0.9 mg/kg) but treatment was stopped in three of them (43%) due to
      nephrotoxicity. Liposomal amphotericin B was given to 81 neonates and
      amphotericin B lipid complex to 29. There were no differences in mortality rate
      and in the incidence of adverse effects in relation to treatment with liposomal
      amphotericin B or amphotericin B lipid complex. The mortality rate was 10.2% and
      all deaths occurred in the VLBW cohort with candidemia.

PMID- 12802716
TI  - A comparative study on the skin penetration of pure tryptanthrin and tryptanthrin
      in Isatis tinctoria extract by dermal microdialysis coupled with isotope dilution
      ESI-LC-MS.
AB  - The indolo[2,1- b]quinazoline alkaloid tryptanthrin has recently been identified
      as a pharmacologically active compound in Isatis tinctoria, with potent dual
      inhibitory activity on prostaglandin and leukotriene synthesis. To investigate
      the skin penetration of tryptanthrin from solutions of pure compound and Isatis
      extracts, we developed and validated a cutaneous microdialysis model using ex
      vivo pig foreleg. Microdialysis was performed by placing linear probes in the
      dermis of the skin in situ, and tryptanthrin concentrations in the dialysates
      were determined by isotope dilution electrospray ionization LC-MS in the selected
      ion mode. Measurable concentrations of tryptanthrin were detected 30 min after
      application. A dose-dependent increase in tryptanthrin concentrations in the
      dialysate was observed for the Isatis extracts, but not for pure tryptanthrin.
      Microscopic analysis showed that the pure compound crystallized from the solution
      but remained in an amorphous state in the extracts.

PMID- 12802717
TI  - Effectiveness and tolerability of a standardized phytodrug derived from Solanum
      chrysotrichum on Tinea pedis: a controlled and randomized clinical trial.
AB  - Superficial mycosis such as Tinea pedis affects between 10 and 15% of the
      population and is amongst the top ten reasons for visiting the doctor in Mexico.
      The vegetal species Solanum chrysotrichum has been, for many years, widely used
      in Mexican traditional medicine for the treatment of fungal foot infections. This
      paper illustrates the results of a controlled and randomized, double-blind
      clinical trial, which compared the therapeutic effect and the tolerability of a
      standardized phytodrug from S. chrysotrichum (experimental group) with 2%
      ketoconazole (control group), applied externally (4 weeks) to 101 patients
      diagnosed with Tinea pedis. After the treatment, the results showed a clinical
      effectiveness (> or = 75% improvement of signs and symptoms) of 96.08 % for the
      group treated with the S. chrysotrichum extract and 91.67% for the ketoconazole
      group (chi 2, p > 0.38); the mycologic effectiveness (direct examination and
      negative culture) was 78.43 % and 77.78%, respectively (chi 2, p > 0.94); whilst
      the tolerability was 100% for both treatments. The therapeutic successes
      (clinical and mycologic effectiveness plus tolerability) was 74.51% with the
      experimental treatment and 69.44% with the control (chi 2, p > 0.60). These
      results support the safety and effectiveness of Solanum chrysotrichum
      standardized phytodrug for the treatment of Tinea pedis.

PMID- 12802718
TI  - Inhibition of xanthine oxidase by phenolic conjugates of methylated quinic acid.
AB  - The caffeoyl conjugates of prenylhydroquinone glucoside and of quinic acid,
      either in the carboxyl-free or carboxymethyl forms, isolated from Phagnalon
      rupestre (Asteraceae), showed inhibitory activity on lipid peroxidation induced
      by Fe 2+/ascorbate and by CCl4/NADPH in rat liver microsomes, with IC50 values
      ranging from 3 to 11 microM. After having demonstrated their effect on the
      xanthine oxidase-regulated superoxide production, the active compounds were
      tested for the direct inhibition of this enzyme. Methylated dicaffeoylquinic
      conjugates competitively inhibited the enzyme and the highest potency was
      obtained for the 4,5-diester, with an IC50 value of 3.6 microM, nearly ten times
      lower than that of the 3,5-analogue. In conclusion, the presence of the caffeoyl
      moiety is essential for both the antiperoxidative and radical scavenging
      activities, and the methylation of the quinic carboxyl group enhances the potency
      on xanthine oxidase inhibitory activity.

PMID- 12802719
TI  - Antitumor activity of balsam fir oil: production of reactive oxygen species
      induced by alpha-humulene as possible mechanism of action.
AB  - The antitumor activity of the essential oil of Abies balsamea (balsam fir oil)
      was evaluated against several solid tumor cell lines including MCF-7, PC-3, A
      549, DLD-1, M4BEU and CT-26. Balsam fir oil was found to be active against all
      the solid tumor cell lines tested, with GI 50 values ranging between 0.76 and 1.7
      mg/mL. The oil was analyzed by GC-MS and the cytotoxicity of each oil constituent
      was determined. Balsam fir oil is essentially constituted of monoterpenes tau; 96
      %) and some sesquiterpenes. All the compounds tested were inactive (tau; 250
      microM) except for alpha-humulene (GI50 = 55 to 73 microM) which thus seems
      responsible for the cytotoxicity of the oil. We also tested the cytotoxicity of
      caryophyllene oxide, which proved inactive, and gamma-caryophyllene which was
      found to be active against all solid tumor cell lines tested. We evaluated the
      effects of balsam fir oil and alpha-humulene on the cellular glutathione (GSH)
      content and on the production of reactive oxygen species (ROS). Balsam fir oil
      and alpha-humulene induced a dose- and time-dependent decrease in cellular GSH
      content and an increase in ROS production. These results suggest that GSH
      depletion and ROS production may be implicated in the cytotoxicity of alpha
      humulene and balsam fir oil.

PMID- 12802720
TI  - Inhibitory effects of furanocoumarins isolated from the roots of Angelica
      dahurica on prostaglandin E2 production.
AB  - We have isolated five furanocoumarins, byakangelicin, phellopterin, imperatorin,
      isoimperatorin, and oxypeucedanin methanolate, from the roots of Angelica
      dahurica (Umbelliferae) and prepared five semi-synthesized compounds by the
      partial reduction of each isolated furanocoumarin, and the effects of these
      compounds on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2 ) production
      in rat peritoneal macrophages were examined. Among these compounds, imperatorin
      showed the most potent inhibitory activity on the LPS-induced PGE2 production. It
      also inhibited the LPS-induced expressions of cyclooxygenase (COX)-2 and
      microsomal prostaglandin E synthase (mPGES). These findings suggest that the
      inhibitory effect of furanocoumarins on the LPS-induced PGE2 production is due to
      the inhibition of the expression of COX-2 and mPGES.

PMID- 12802721
TI  - Antimicrobial and antioxidant activities of three Mentha species essential oils.
AB  - The present study describes the antimicrobial activity and free radical
      scavenging capacity (RSC) of essential oils from Mentha aquatica L., Mentha
      longifolia L., and Mentha piperita L. The chemical profile of each essential oil
      was determined by GC-MS and TLC. All essential oils exhibited very strong
      antibacterial activity, in particularly against Esherichia coli strains. The most
      powerful was M. piperita essential oil, especially towards multiresistant strain
      of Shigella sonei and Micrococcus flavus ATTC 10,240. All tested oils showed
      significant fungistatic and fungicidal activity [expressed as minimal inhibitory
      concentration (MIC) and minimal fungicidal concentration (MFC) values,
      respectively], that were considerably higher than those of the commercial
      fungicide bifonazole. The essential oils of M. piperita and M. longifolia were
      found to be more active than the essential oil of M. aquatica. Especially low MIC
      (4 microL/mL) and MFC (4 microL/mL) were found with M. piperita oil against
      Trichophyton tonsurans and Candida albicans (both 8 microL/mL). The RSC was
      evaluated by measuring the scavenging activity of the essential oils on the 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and OH radicals. All examined essential oils
      were able to reduce DPPH radicals into the neutral DPPH-H form, and this activity
      was dose-dependent. However, only the M. piperita oil reduced DPPH to 50 % (IC50
      = 2.53 microg/mL). The M. piperita essential oil also exhibited the highest OH
      radical scavenging activity, reducing OH radical generation in the Fenton
      reaction by 24 % (pure oil). According to GC-MS and TLC (dot-blot techniques),
      the most powerful scavenging compounds were monoterpene ketones (menthone and
      isomenthone) in the essential oils of M. longifolia and M. piperita and 1,8
      cineole in the oil of M. aquatica.

PMID- 12802722
TI  - Antifungal, antiprotozoal, cytotoxic and piscicidal properties of Justicidin B
      and a new arylnaphthalide lignan from Phyllanthus piscatorum.
AB  - Using activity against Candida albicans as a lead, the bioactivity-guided
      fractionation of the dichloromethane extract of Phyllanthus piscatorum led to the
      isolation of the arylnaphthalide lignan justicidin B (1), which was found to be
      present in high amounts, and a new C-11 hydroxylated derivative that we named
      piscatorin (2). We provide evidence that justicidin B (1) is the main active
      principle of P. piscatorum, showing the same biological effects that were found
      for the raw extracts. Justicidin B inhibited the growth of the pathogenic fungi
      Aspergillus fumigatus (MIC > or = 1 microg/mL), Aspergillus flavus (MIC > or = 12
      microg/mL), and Candida albicans (MIC > or = 4 microg/mL), but was not effective
      against Cryptococcus neoformans and Blastoschizomyces capitatus. Justicidin B
      also exhibited strong activity against the trypomastigote form of Trypanosoma
      brucei rhodesiense (IC50 = 0.2 microg/mL) and moderate activity against
      Trypanosoma cruzi (IC50 = 2.6 microg/mL). Testing against Plasmodium falciparum
      showed only weak activity. This is the first report on the in vitro fungicidal
      and antiprotozoal effects of justicidin B. In addition, both compounds exhibited
      a non-specific cytotoxicity in neoplastic and primary cell cultures. No
      antibacterial effects were detected. Both compounds were piscicidal against zebra
      fish and it is shown for the first time that piscatorin (2) and justicidin B (1)
      are the piscicidal principles of P. piscatorum, exhibiting a potency that is
      comparable to rotenone.

PMID- 12802723
TI  - The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia
      rutaecarpa in mice.
AB  - Recently, the authors reported that evodiamine, a major alkaloidal principle of
      Evodia fruits (Evodia rutaecarpa, Rutaceae), had vanilloid receptor agonistic
      activity comparable to capsaicin. In spite of the similarities in the actions of
      evodiamine and capsaicin in vitro, the effects of evodiamine on sensory neurons
      in vivo had not been investigated. We demonstrate here that evodiamine sensitizes
      and desensitizes the capsaicin-sensitive sensory afferents in mice, resulting in
      nociceptive action and antinociceptive actions. The nociceptive action (paw
      licking behaviour) was dose dependently induced by intradermal injection (i.d.)
      of evodiamine to the hind paw and was suppressed by the co-treatment with
      capsazepine, a vanilloid receptor specific agonist, in a dose-dependent manner.
      The treatment with higher dosages of evodiamine showed sustained antinociceptive
      effects. The acetic acid-induced writhing was significantly suppressed by the
      intraperitoneal evodiamine administration 3 days before, without any observable
      effects on spontaneous motor activity. The response of the isolated ileum from
      the mice with or without high dosages of evodiamine administration indicated the
      sensory neuron specific desensitizing effect of evodiamine. The isolated ileum
      from vehicle-treated mice contracted in response to both the sensory nerve
      stimulation by 10 microM capsaicin and the mimicked vagal stimulation by 2 microM
      carbachol. However, the isolated ileum from evodiamine-treated mice lost its
      response to sensory nerve stimuli but retained its response to vagus nerve
      stimuli. The suppression of acetic acid-induced writhing and the desensitization
      of visceral sensory neurons strongly correlated [regression coefficient (r) =
      0.955]. Thus, we demonstrate that evodiamine shows the analgesic action by
      desensitizing sensory nerves.

PMID- 12802724
TI  - Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies.
AB  - Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from
      Carthamus tinctorius L. markedly extended the coagulation time in mice and
      exhibited a significant antithrombotic effect in rats. The present study was
      conducted to demonstrate further its neuroprotective effects on cerebral ischemic
      injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY)
      rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological
      deficit scores followed by the treatment with a single dose of HSYA. Furthermore,
      the infarction area of the brain was assessed in the brain slices. In vitro, the
      effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate
      and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage.
      The results in vivo showed that sublingular vein injection of HSYA at doses of
      3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with
      focal cerebral ischemic injury by significantly decreasing neurological deficit
      scores and reducing the infarct area compared with the saline group, HSYA at a
      dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg.
      Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a
      neuroprotective effect, however, with no significant difference when compared
      with the saline group. Results in vitro showed that HSYA significantly inhibited
      neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in
      cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on
      glutamate-mediated neuron injury was much better than that of HSYA on NaCN
      induced neuron damage. All these findings suggest that HSYA might act as a
      potential neuroprotective agent useful in the treatment in focal cerebral
      ischemia. Abbreviations. HSYA:hydroxysafflor yellow A TTC:2,3,5
      triphenyltetrazolium chloride MTT:3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliumbromide DMEM:Dulbecco's modified Eagle medium FCS:Fetal calf
      serum MCAO:middle cerebral artery occlusion ECA:external carotid artery
      ICA:internal carotid artery LDH:lactate dehydrogenase NMDA: N-methyl- D-aspartate

PMID- 12802725
TI  - Diterpenoid and phenolic glycosides from the roots of Rhododendron molle.
AB  - Two new grayanane diterpenoid glucosides, rhodomosides A (1), B (2) and two new
      phenolic glycosides 3, 4 together with a known glucosyringic acid (5) were
      isolated from the roots of Rhododendron molle G. Don (Ericaceae). Their
      structures were elucidated on the basis of spectral analysis. Compounds 3, 4 and
      5 were found to inhibit the proliferation of murine B lymphocytes in vitro, while
      compound 3 also showed stimulatory activity on the proliferation of murine T
      lymphocytes in vitro.

PMID- 12802726
TI  - New cytotoxic oleanane saponins from the infructescences of Polyscias amplifolia
      from the Madagascar rainforest.
AB  - Bioassay-guided fractionation of an ethanolic extract of the infructescences of
      Polyscias amplifolia resulted in the isolation of two new oleanolic acid
      saponins, polyfoliolides A (1) and B (2), in addition to the two known saponins 3
      O-beta-D-galactopyranosyloleanolic acid (3) and 3-O-beta-D-galactopyranosyl-(1-
      >4)-beta-D-galactopyranosyloleanolic acid (4). The structures of the two new
      compounds were established as 3-O-beta- D-galactopyranosyl-(1-->4)-beta-D
      xylopyranosyloleanolic acid (1) and 3-O-beta-D-galactopyranosyl-(1-->4)-alpha-L
      arabinopyranosyloleanolic acid (2) on the basis of extensive 1D and 2D NMR
      spectroscopic data interpretation and chemical conversions. All the isolated
      compounds showed weak cytotoxicity against A2780 human ovarian cancer cell line,
      with IC50 values in the range 6.7 to 10.8 microg/mL.

PMID- 12802727
TI  - Simultaneous analysis of seventeen chemical ingredients of Ligusticum chuanxiong
      by on-line high performance liquid chromatography-diode array detector-mass
      spectrometry.
AB  - An on-line high performance liquid chromatography (HPLC)-diode array detector
      (DAD)-mass spectrometry (MS) analytical method has been developed to
      simultaneously separate and identify seventeen main constituents of Chuanxiong (
      Ligusticum chuanxiong Hort.), a traditional Chinese medicinal herb. In three
      Chuanxiong samples, nine compounds were unequivocally determined as vanillin (1),
      ferulic acid (2), senkyunolide I (4), senkyunolide H (5), senkyunolide A (6),
      coniferyl ferulate (7), Z-ligustilide (8), neocnidilide (9) and 3
      butylidenephthalide (10) by comparing their t R, UV, and MS data with those
      obtained for the authentic compounds. Furthermore, additional eight compounds
      were tentatively identified as senkyunolide J (11), senkyunolide F (12), 3
      butylphthalide (13), cnidilide (14), riligustilide (15) or Z,Z'-6,8',7,3'
      diligustilide (16), tokinolide B (17), levistolide A (18) and senkyunolide P
      (19), based on their MS data and the comparison of their UV spectra with the
      published references. This is the first report to describe the development of an
      on-line HPLC-DAD-MS method to simultaneously analyse seventeen main constituents
      present in Chuanxiong and to construct the chemical profiles of various
      Chuanxiong samples.

PMID- 12802728
TI  - Quantification of the flavonoid glycosides in Passiflora incarnata by capillary
      electrophoresis.
AB  - Capillary electrophoresis has been applied for the separation and quantification
      of the flavonoids in Passiflorae herba. Separations were performed using 25 mM
      sodium borate with 20 % methanol (pH 9.5). For the quantification quercetin 3-O
      arabinoside was used as internal standard. The method was applied to the
      determination of the flavonoid glycosides in 10 different commercial samples of
      the drug and showed similar flavonoid patterns, but differences concerning the
      single and total amounts of flavonoids. The total flavonoid contents determined
      with the new method correlated satisfactorily with those achieved by the
      spectrophotometric assay according to the European Pharmacopoeia.

PMID- 12802729
TI  - Kinobeon A as a potent tyrosinase inhibitor from cell culture of safflower: in
      vitro comparisons of kinobeon A with other putative inhibitors.
AB  - Kinobeon A is produced from cell cultures of the medicinal plant, safflower.
      Mushroom tyrosinase activity was inhibited in a concentration-dependent manner
      when treated with kinobeon A using L-tyrosine or L-3,4-dihydroxyphenylalannine (L
      DOPA) as substrates. IC50 values were 22 microM (substrate: L-tyrosine) and 27
      microM (L-DOPA). Inhibition of human tyrosinase activity also increased with
      increasing concentrations of kinobeon A using L-DOPA as the substrate, with an
      IC50 value of 2.5 microM. Kinobeon A was a more potent competitive inhibitor than
      kojic acid, arbutin or L-ascorbic acid for both mushroom and human tyrosinase as
      determined from Lineweaver-Burk plots. These results suggested that kinobeon A
      could be a potent natural tyrosinase inhibitor.

PMID- 12802731
TI  - New cytotoxic sesquiterpene lactones from Warionia saharae.
AB  - Cytotoxicity-guided fractionation of the methanol soluble part of the
      dichloromethane extract of the leaves of Warionia saharae led to the isolation of
      the two new guaianolide-type sesquiterpene lactones, 5 alpha H-3 beta,4 beta
      epoxy-14-oxo-guaia-1(10),11(13)-dien-6 alpha,12-olide (1), 5 alpha H-2 beta,4
      beta-epoxy-3 alpha-hydroxy-guaia-1(10),11(13)-dien-6 alpha,12-olide (6), and the
      new eudesmane type sesquiterpene 1 beta,6 alpha-dihydroxycostic acid ( 4). In
      addition, the known sesquiterpene lactones 5 alpha H-2 beta-hydroxyguaia
      3(4),10(14),11(13)-trien-6 alpha,12-olide (2), reynosin (3), 5 alpha H-1 alpha,10
      alpha:3 alpha,4 alpha-diepoxyguaia-11(13)-en-6 alpha,12-olide (5), and
      dehydroleucodin (7) were isolated together with the known flavone hispidulin.
      Cytotoxicity testing of the sesquiterpene lactones against the KB cancer cell
      line (ATCC CCL17) revealed IC50 values of 3.5 (1), 2.6 ( 2), 2.7 ( 3), 4.3 ( 5),
      3.6 ( 6), and 1.3 (7) microg/mL. Compound 4 was not active up to 20 microg/mL.

PMID- 12802730
TI  - Torilin from Torilis japonica, as a new inhibitor of testosterone 5 alpha
      reductase.
AB  - The methanolic extract of the fruits of Torilis japonica showed a potent
      inhibition against 5 alpha-reductase activity in vitro. Bioassay-guided
      fractionation of the methanol extract of the fruits followed by repeated silica
      gel chromatography led to the isolation of an active principle and its structure
      was identified as torilin on the basis of spectroscopic data. Torilin (IC50 =
      31.7 +/- 4.23 microM) showed a stronger inhibition of 5 alpha-reductase than
      alpha-linolenic acid (IC50 = 160.3 +/- 24.62 microM) but was weaker than
      finasteride. (IC50 = 0.38 +/- 0.06 microM). Simple guaiane-type compounds, such
      as (-)-guaiol and guaiazulene showed weak inhibitory effects on the 5 alpha
      reductase activity with IC50 values of f 81.6 microM and 100.8 microM,
      respectively, while azulene was not active. These results suggest that both
      degrees of unsaturation and the side-chain in the guaiane skeleton are important
      for the manifestation of 5 alpha-reductase inhibition.

PMID- 12802732
TI  - Studies on di- and triterpenoids from Salvia staminea with cytotoxic activity.
AB  - A new ursane-type triterpenoid, 3 beta,11 alpha,21 alpha-trihydroxyurs-12-ene,
      named salvistamineol (1), has been isolated from the methanol extract of Salvia
      staminea. In addition to 1, the methanol extract yielded four known compounds and
      the acetone extract yielded twelve known compounds consisting of two
      sesquiterpenes, six diterpenoids, a triterpenoid, two steroids and one flavone.
      DNA damaging properties of the extracts and some isolated diterpenes were
      investigated against three yeasts and only taxodione gave a positive response and
      also showed the highest cytotoxic activity against a panel of cell lines among
      the investigated compounds in this study.

PMID- 12802733
TI  - Antimicrobial diterpenes from the seeds of Cephalotaxus harringtonia var.
      drupacea.
AB  - Six diterpenes, including two new natural products, were isolated from the seeds
      of Cephalotaxus harringtonia. The new metabolites were characterised as 8 beta
      hydroxy-9(11),13-abietadien-12-one and 5,6-didehydroferruginol, while the known
      compounds were identified as ferruginol, sugiol, 6,12-dihydroxyabieta-5,8,11,13
      tetraen-7-one, and abieta-8,11,13-trien-7 beta-ol. These compounds were studied
      in vitro for their antimicrobial activity against clinically isolated bacteria
      and Candida strains. Ferruginol and 6,12-dihydroxyabieta-5,8,11,13-tetraen-7-one
      showed antimicrobial activity against Gram-positive bacteria. None of the six
      diterpenes was active against the Gram-negative organisms and yeasts tested.

PMID- 12802734
TI  - In vitro trypanocidal activity of triterpenes from miconia species.
AB  - The bioassay-guided fractionation of methylene chloride extracts of Miconia
      fallax DC. and Miconia stenostachya DC. led to the isolation of five triterpene
      acids. The triterpenes ursolic acid, oleanolic acid and gypsogenic acid were
      active against blood trypomastigote forms of Trypanosoma cruzi. In contrast, the
      acetyl and methyl ester derivatives were not found to potentiate the trypanocidal
      activity. These results suggest the importance of the polar groups for activity.

PMID- 12802735
TI  - Antioxidant activity of maslinic acid, a triterpene derivative obtained from Olea
      europaea.
AB  - We investigated the effect of maslinic acid (a triterpene derivative obtained
      from olive pomace), on the susceptibility of plasma or hepatocyte membranes to
      lipid peroxidation (LPO), induced respectively by the hydroxyl radical (OH*)
      generated by Fe2+/H2O2 ex vivo and by the system Fe3+/ascorbate in vitro;
      moreover, three groups of animals used in the plasma study were pretreated with
      CCl4 (to generate CCl3-*). Endogenous plasma lipoperoxide levels and
      susceptibility to LPO were decreased in rats treated with maslinic acid, after
      exposure to OH* by Fe2+/H2O2 (Fenton reaction). Co-incubation with maslinic acid
      prevented hepatocyte membrane LPO as shown by the reduction of TBARS. In
      conclusion, maslinic acid may offer some advantages in the resistance of
      oxidative stress in the animals.

PMID- 12802738
TI  - Embryoidogenesis and plant regeneration from leaf tissue of Gloriosa superba.
AB  - The induction, maturation and germination of embryoids from leaf tissue of
      Gloriosa superba L. were developed by exploiting solid and liquid culture.
      Nodular calli were obtained from SH medium supplemented with 2,4-D and 2iP. In
      solid culture, the nodular calli when transferred to 2,4-D along with glycerol
      gave the best response (68.4 %) in embryoid induction after 20 days. After two
      subcultures at 7-day intervals in a medium with thiamine instead of glycerol, the
      embryoids matured. When mature embryoids were transferred to BAP and IBA medium,
      they gave rise to plantlets with single shoots and roots. In liquid culture, the
      medium supplemented with NAA and L-glutamine with continuous agitation, the
      embryoidogenic calli produced embryoids (85 %) after 21 days. The mature
      embryoids began to turn green and produced shoots and elongated "radicles" after
      35 days.

PMID- 12802736
TI  - Anti-inflammatory action of legume isoflavonoid sophoricoside through inhibition
      on cyclooxygenase-2 activity.
AB  - Soy is a main source of isoflavonoids which are of high dietary intake for the
      oriental population. In this study, the anti-inflammatory action of
      sophoricoside, an isoflavone glycoside isolated from immature fruits of Sophora
      japonica L. (Leguminosae), has been demonstrated. When administered orally at >
      100 mg/kg or injected intravenously at > 10 mg/kg, sophoricoside showed
      significant reduction of carrageenin-induced paw edema in mice. Sophoricoside has
      been identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with
      an IC50 value of 3.3 microM.

PMID- 12802737
TI  - Variation of podophyllotoxin in leaves of Eastern Red Cedar (Juniperus
      virginiana).
AB  - Leaves of Eastern red cedar (Juniperus virginiana L. Cupressaceae) have been
      reported to contain podophyllotoxin, a pharmaceutical compound used to
      manufacture drugs for treatment of cancer, rheumatoid arthritis, genital warts,
      psoriasis, and multiple sclerosis. Podophyllotoxin content of leaves of immature,
      mature male, and mature female plants (approximately 1.45 mg x g -1) was
      significantly higher than that of leaves of juvenile plants (0.60 mg x g -1).
      Sampling date also affected podophyllotoxin content. Leaves harvested in January
      and April exhibited higher podophyllotoxin contents (1.56 and 1.45 mg x g -1,
      respectively) than leaves harvested in February and June (1.06 and 1.08 mg x g 
      1, respectively). There was no obvious pattern or trend in the data due to
      sampling date. There was no significant interaction between plant type and
      sampling date. These results indicate that foliage of mature Eastern red cedar, a
      waste product of the lumber industry, could be a low-yielding, but relatively
      stable, source of podophyllotoxin.

PMID- 12802739
TI  - Absolute configuration of keisslone, a new antimicrobial metabolite from
      Keissleriella sp. YS4108, a marine filamentous fungus.
AB  - In order to purify enough material for establishing the absolute stereochemistry
      of the new antifungal metabolite 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)
      heptenyl]-2,3-dihydronaphthalen-1(4H)-one produced by Keissleriella sp., a marine
      filamentous fungus (strain number: YS 4108), a repeated growth and fractionation
      of the fungal culture was performed to give instead a new antimicrobial
      metabolite, keisslone (1), the structure of which was elucidated on the basis of
      spectral analyses including homo- and hetero-nuclear correlation NMR experiments
      (HMQC, COSY, NOESY and HMBC). The absolute configuration of metabolite 1 was
      determined mainly by its CD data and NOESY spectrum. The compound 1 was shown to
      be inhibitory against the human pathogenic fungi Candida albicans, Trichophyton
      rubrum and Aspergillus niger with MICs of 50, 70, 40 microg/mL, respectively. In
      order to purify enough material for establishing the absolute stereochemistry of
      the new antifungal metabolite 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)
      heptenyl]-2,3-dihydronaphthalen-1(4 H)-one produced by Keissleriella sp., a
      marine filamentous fungus (strain number: YS 4108), a repeated growth and
      fractionation of the fungal culture was performed to give instead a new
      antimicrobial metabolite, keisslone (1), the structure of which was elucidated on
      the basis of spectral analyses including homo- and hetero-nuclear correlation NMR
      experiments (HMQC, COSY, NOESY and HMBC). The absolute configuration of
      metabolite 1 was determined mainly by its CD data and NOESY spectrum. The
      compound 1 was shown to be inhibitory against the human pathogenic fungi Candida
      albicans, Trichophyton rubrum and Aspergillus niger with MICs of 50, 70, 40
      microg/mL, respectively.

PMID- 12802740
TI  - Separation and determination of coumarins in the root bark of three citrus plants
      by micellar electrokinetic capillary chromatography.
AB  - A micellar electrokinetic capillary chromatography (MEKC) method for the
      determination of xanthyletin and xanthoxyletin in the roots bark of three Citrus
      plants was developed for the first time. The electrophoresis buffer was 10 mmol/L
      sodium borate containing 50 mmol/L sodium dodecyl sulfate, 20% (v/v) acetonitrile
      and 10 % (v/v) methanol (pH 9.8). The correlation coefficients of the calibration
      curves for xanthyletin and xanthoxyletin are 0.9993 and 0.9999, respectively,
      over the concentration ranges (16.0-800.0 mg/L; 8.0-400.0 mg/L).

PMID- 12802741
TI  - [Effect of molsidomine on rheological parameters and the incidence of
      cardiovascular events].
AB  - BACKGROUND AND OBJECTIVE: In-vitro studies revealed that nitric oxide (NO) may
      affect rheological parameters. We studied the effect of highly-dosed NO-donor
      molsidomine on blood rheology and the impact of rheological parameters on the
      incidence of severe cardiovascular events. PATIENTS AND METHODS: In this
      randomized, placebo-controlled and double-blind trial 166 patients (60 +/- 10
      years) with stable angina pectoris and coronary intervention received molsidomine
      3 x 8 mg t. i. d. (controlled release tablets) or placebo for 6 months. Patients
      with inflammatory/neoplastic disorders or elevated values of C-reactive protein
      were excluded from analysis. A rheological profile (plasma viscosity, blood
      viscosity, aggregation and flexibility of erythrocytes, filtrability of
      leukocytes, fibrinogen levels) was done initially and after 6 months. Adverse
      cardiovascular events (death, myocardial infarction, stroke, coronary/peripheral
      revascularization) were recorded during 12 months. Furthermore, the impact of
      rheological parameters regarding the occurrence of severe cardiovascular events
      (death, myocardial infarction, stroke) was evaluated during a follow-up of median
      38 months. RESULTS: The data of 137 patients (n = 71 placebo, n = 66 molsidomine)
      were analysed. The difference of rheological parameters between the two
      measurements did not vary between the two groups. Analysis of event-free survival
      with Kaplan-Meier technique revealed no difference between the two groups.
      Multivariate Cox regression analysis with adjustment for diabetes mellitus,
      smoking and therapy with statin showed a significant association of fibrinogen
      and plasma viscosity with the occurrence of severe cardiovascular events.
      CONCLUSION: Treatment with molsidomine 3 x 8 mg/day for 6 months does not improve
      blood rheology or reduce cardiovascular events. But elevated levels of fibrinogen
      and plasma viscosity were associated with the occurrence of severe cardiovascular
      events.

PMID- 12802742
TI  - [The medical profession against Anglicization in medicine. Results of a survey].
AB  - BACKGROUND AND OBJECTIVE: The growing Anglicization of the German language
      especially affects medicine. This is true not only in medical research but also
      for congresses and publications. This leads to far-reaching consequences also for
      continuing medical education. This questionnaire study obtained the opinions by a
      selected group of doctors attending a general medical congress. METHODS:
      Questionnaires were distributed to 365 attendees of the 51. Doctors' Congress in
      Berlin in June 2002. In addition 345 questionnaires were sent to doctors working
      at 3 university clinics, 27 clinics at teaching hospitals and 9 at communal
      clinics throughout Germany. Answers were divided by work place (clinical or non
      clinical) and age. RESULTS: There were 360 respondents (188 non-clinical, 172
      clinical; 51.1%): 20% reported good self appraised knowledge of written and
      spoken English. 84.7% were against English as the only language at meetings of
      German medical societies, while 98.3% were against it for national congresses
      (except for foreign guests). 84.3% agreed that German and English should be the
      languages, both of talks and discussions, at international congresses held in
      Germany. English as the language of specialist journals was less strongly
      rejected by young respondents. There was no age-related difference regarding the
      other questions. CONCLUSIONS: The respondents considered it as self-evident that
      German be the only language at German national congresses and of journals by
      German publishers directed at German doctors, but certain exception were
      acceptable. At international congresses held in Germany, both German and English
      are equally acceptable in order to avoid a large part of the interested German
      medical community being disadvantaged in their acquisition of medical-scientific
      information were English to be the sole language.

PMID- 12802743
TI  - [Thin-walled apical ventricular aneurysm associated with hypertrophic obstructive
      cardiomyopathy].
AB  - HISTORY AND ADMISSION FINDINGS: A 73-year-old patient presented for routine
      follow-up examination for pre-diagnosed hypertrophic obstructive cardiomyopathy
      (HOCM). The patient's history included arterial hypertension and dyspnea on
      exertion. INTERVENTIONS: Echocardiography revealed a large apical aneurysm, which
      had vastly increased in size over the past six months. Further evaluation by
      cardiac magnetic resonance (NMR) imaging confirmed the aneurysm and demonstrated
      a wall thickness of no more than 2 mm. TREATMENT AND COURSE: Due to the rapid
      increase in size in addition to the extremely thin wall diameter the risk of
      spontaneous rupture was considered high and the patient was referred to surgical
      therapy. Echocardiographic and NMR-findings were confirmed intraoperatively. The
      aneurysm was resected and the postoperative progress was uneventful. CONCLUSION:
      Aneurysms of the apical left ventricle can result from an underlying HOCM. In
      case of rapid increase of the aneurysm, aneurysmectomy should be performed.

PMID- 12802744
TI  - [A 47-year-old man with "pure autonomic failure" and pernicious anemia].
AB  - HISTORY AND CLINICAL FINDINGS: A 47-year-old man with a known and substituted
      vitamin B12 deficiency presented with increasing symptoms associated with
      orthostatic hypotension, neck pain and micturitional and visual disturbances.
      CLINICAL AND LABORATORY TESTS: Catecholamines were strongly reduced in plasma and
      urine. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: A pure autonomic failure was
      diagnosed and therapy with fludrocortisone, yohimbine and erythropoetine was
      started. Symptoms with the exception of micturitional disturbances improved
      strongly. CONCLUSIONS: Multiple-drug treatment of pure autonomic failure is
      successful. The prognosis is good.

PMID- 12802745
TI  - [Risperidone].

PMID- 12802746
TI  - [Acute and chronic inflammatory neuropathies--diagnosis].

PMID- 12802747
TI  - ["Ecstasy" (MDMA): pharmacology, toxicology, and treatment of acute
      intoxication].

PMID- 12802748
TI  - Ceftriaxone compared with sodium penicillin g for treatment of severe
      leptospirosis.
AB  - A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was
      conducted from July 2000 through December 2001 to compare the clinical efficacies
      of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis.
      A total of 173 patients with severe leptospirosis were randomly assigned to be
      treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or
      intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86). The
      primary outcome was time to fever resolution. Survival analysis demonstrated that
      the median duration of fever was 3 days for both groups. Ten patients (5 in each
      group) died of leptospirosis infection. There were no statistically significant
      differences in the duration of organ dysfunction. Ceftriaxone and sodium
      penicillin G were equally effective for the treatment of severe leptospirosis.
      Once-daily administration and the extended spectrum of ceftriaxone against
      bacteria provide additional benefits over intravenous penicillin.

PMID- 12802749
TI  - A mountain out of a molehill: do we treat acute leptospirosis, and if so, with
      what?

PMID- 12802750
TI  - Comparison of 12-month courses of interferon-alpha-2b-lamivudine combination
      therapy and interferon-alpha-2b monotherapy among patients with untreated chronic
      hepatitis B.
AB  - We compared the use of prolonged synchronous combination therapy with interferon
      (IFN)-alpha-2b and lamivudine with the use of IFN-alpha-2b monotherapy in
      patients with untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis
      B virus (HBV) infection. Thirty-three patients received therapy with lamivudine
      (100 mg daily) and IFN-alpha-2b (10 million U 3 times per week) for 12 months; 16
      patients received IFN-alpha-2b alone (10 million U 3 times per week for 12
      months). The primary end point was sustained suppression of HBV DNA and HBeAg
      seroconversion, which was observed in 15 (45%) of 33 patients treated with
      combination therapy and in 3 (19%) of 16 patients treated with monotherapy
      (P=.133). Both therapeutic regimens were well tolerated. Combination therapy
      increased the rate of sustained suppression of HBeAg and resulted in significant
      improvement in Knodell histologic activity index scores, compared with
      monotherapy. However, there was no significant difference in rates of sustained
      suppression between the 2 groups at the end of follow-up.

PMID- 12802751
TI  - Efficacy and safety of oral pleconaril for treatment of colds due to
      picornaviruses in adults: results of 2 double-blind, randomized, placebo
      controlled trials.
AB  - The novel capsid-binding antiviral pleconaril inhibits in vitro replication of
      most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2
      parallel randomized, double-blind, placebo-controlled trials. Among 1363
      picornavirus-infected participants (65%) in the studies combined, the median time
      to alleviation of illness was 1 day shorter for pleconaril recipients than for
      placebo recipients (P<.001). Cold symptom scores and frequency of picornavirus
      cultured from nasal mucus specimens were lower among pleconaril recipients by day
      2 of treatment. No treatment effects were seen in those without picornavirus
      infection. Pleconaril was associated with a higher incidence of nausea (6% vs.
      4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol
      levels and platelet counts, compared with baseline measurements. A subsequent 6
      week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes,
      which metabolize a variety of drugs, including ethinyl estradiol. Early
      pleconaril treatment was well tolerated and significantly reduced the duration
      and severity of colds due to picornaviruses in adults.

PMID- 12802752
TI  - Monocyte and lymphocyte apoptosis resistance in acute and chronic brucellosis and
      its possible implications in clinical management.
AB  - This study evaluated the level of susceptibility of monocytes and lymphocytes to
      spontaneously induced and CH11-induced apoptosis in 16 patients with Brucella
      infection. The expression of some immunological and apoptotic markers was
      evaluated. Before therapy, monocytes showed a high level of resistance to
      spontaneously induced or CH11-induced apoptosis in all patients. In patients with
      acute infection, this resistance persisted for 10-20 days after treatment was
      initiated, then decreased; in chronically infected patients, it persisted after
      45 days of treatment. Lymphocytes were also more resistant to CH11-induced
      apoptosis. The level of activated CD8(+) T lymphocytes was high in patients with
      acute infection. The data indicate that the CD95-mediated apoptotic pathway is
      not involved in CH11 resistance. Lymphocytes are not infected by Brucella, so
      their resistance to apoptosis may be due to a soluble factor released by infected
      monocytes. The evaluation of levels of susceptibility to CH11-induced apoptosis
      in monocytes may be used to test the effectiveness of the therapy.

PMID- 12802753
TI  - Prophylaxis against dialysis catheter-related bacteremia with a novel
      antimicrobial lock solution.
AB  - Catheter-related bacteremia, a frequent complication in patients who are
      undergoing hemodialysis, may be prevented by eradication of the catheter biofilm.
      Catheter lock solution (CLS) is an investigational preparation containing
      taurolidine, a biocompatible antimicrobial agent, and citrate, an anticoagulant
      agent. CLS was instilled into the catheter lumens after each dialysis session for
      20 catheter-dependent hemodialysis patients. Catheter outcomes were compared with
      those observed in 30 concurrent control patients whose catheters were instilled
      with heparin. Bacteremia-free survival at 90 days was higher among patients who
      received CLS than among control patients who received heparin (94% vs. 47%;
      P<.001). Unassisted catheter patency (without tissue plasminogen activator
      instillation) was lower among patients who received CLS than among control
      patients (32% vs. 76%; P<.001). CLS dramatically reduces the frequency of
      catheter-related bacteremia among patients undergoing hemodialysis, although
      there is an increased requirement for thrombolytic interventions to maintain
      catheter patency.

PMID- 12802754
TI  - Consent and compensation: a social compact for smallpox vaccine policy in the
      event of an attack.
AB  - In the event of a widespread biological attack involving smallpox, it may not
      only be morally permissible, but morally obligatory, to dispense with the
      ordinary requirements of informed consent for vaccination. The government should
      also commit to educating the public about the vaccine, distributing the vaccine
      efficiently and fairly, and ensuring access to health care to those who
      experience adverse events as a result of vaccination. In addition, the government
      should provide a program of financial compensation for any persons who experience
      permanent disability as a consequence of vaccination and for the families of
      those who die as a result of vaccination.

PMID- 12802755
TI  - Pandemic influenza and the global vaccine supply.
AB  - Use of influenza vaccine is increasing, especially in developing countries. Yet
      most of the world's influenza vaccine is produced by companies located in 9
      developed countries. When the threat of an influenza pandemic appears, the
      traditional approach to providing interpandemic vaccines will not be able to meet
      the global demand for pandemic vaccine. Several steps must be taken to address
      this problem, including the use of reverse genetics to prepare seed strains for
      vaccine production, the undertaking of clinical studies to define the
      characteristics of candidate "pandemic-like" vaccines and vaccination schedules,
      the development of procedures for global vaccine registration, the expansion of
      recommendations and reimbursement for interpandemic vaccination, the country
      specific reporting of vaccine use and forecasts of future vaccine needs, and the
      negotiation of political agreements that will ensure the adequate production and
      equitable distribution of pandemic vaccine throughout the world.

PMID- 12802756
TI  - Vaccination for pandemic influenza and severe acute respiratory syndrome: common
      issues and concerns.

PMID- 12802757
TI  - Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for
      treatment of chronic hepatitis C in human immunodeficiency virus-coinfected
      patients.
AB  - An open-label, randomized trial was conducted to compare the efficacy and safety
      of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management
      of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus
      (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN
      alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks,
      followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31
      patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22
      weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients).
      Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week
      12. Sustained virological response was achieved in 10 patients (15%; 6 in group A
      and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3
      log(10) copies/mL between inclusion and week 4 were associated with virological
      response. In conclusion, the combination of conventional IFN-alpha-2a and
      ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.

PMID- 12802758
TI  - Adherence to directly observed antiretroviral therapy among human
      immunodeficiency virus-infected prison inmates.
AB  - Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection
      is commonly used in correctional settings; however, the efficacy of DOT for
      treating HIV infection has not been determined. We prospectively assessed
      adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates
      who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self
      report, pill count, electronic monitoring caps, and, for DOT only, medication
      administration records. Overall, median adherence was 90%, as measured by pill
      count; 86%, by electronic monitoring caps; and 100%, by self-report. Adherence,
      as measured by electronic monitoring caps, was >90% in 32% of the subjects. In
      91% of cases, adherence, as measured by medication administration records, was
      greater than that recorded by electronic monitoring caps for the same medications
      administered by DOT. Objective methods of measurement revealed that adherence to
      antiretroviral regimens administered wholly or in part by DOT was <or=90% in more
      than one-half of the patients. Different methods used to measure adherence
      revealed significantly different levels of adherence. These findings suggest that
      use of DOT does not ensure adherence to antiretroviral therapy.

PMID- 12802759
TI  - Effect of physician specialty on counseling practices and medical referral
      patterns among physicians caring for disadvantaged human immunodeficiency virus
      infected populations.
AB  - Data regarding the care and management of human immunodeficiency virus (HIV)
      infected patients provided by infectious diseases (ID)-trained physicians,
      compared with data for care and management provided by other specialists, are
      limited. Here, we report results of a self-administered survey sent to 317
      physicians (response rate, 76%) in 4 metropolitan areas of the United States who
      were identified as providing care to disadvantaged HIV-infected patients. ID
      trained physicians who responded that they strongly agreed or somewhat agreed
      that they had enough time to care for their HIV-infected patients were more
      likely than were non-ID-trained physicians to provide therapy-adherence
      counseling. Physicians with >or=50 patients in care and ID-trained physicians
      were less likely to always discuss condom use and risk reduction for HIV
      transmission. Factors significantly associated with referring rather than
      treating HIV-infected patients with hypertension or diabetes included having <50
      patients in care, being an ID-trained physician, and practicing in a private
      practice. These results suggest the need for targeted physician training on the
      importance of HIV transmission prevention counseling, increasing the duration of
      patient visits, and improving strategies for generalist-specialist comanagement
      of HIV-infected patients.

PMID- 12802760
TI  - A review of low-dose ritonavir in protease inhibitor combination therapy.
AB  - The pharmacokinetics of protease inhibitors center around the microsomal enzyme
      cytochrome P-450 3A4. As a potent inhibitor of this enzyme, ritonavir can
      increase the bioavailability and half-life of coadministered protease inhibitors.
      Evidence suggests that increased exposure to protease inhibitors is clinically
      relevant. Antiretroviral treatment with low-dose ritonavir-boosted lopinavir,
      indinavir, and saquinavir has durable virological activity and shows impressive
      immune reconstitution. Although tolerable in most cases, gastrointestinal side
      effects, hepatotoxicity, and blood lipid abnormalities remain relevant issues.
      Additional study will elucidate the advantages and disadvantages of twice-daily,
      low-dose ritonavir-boosted regimens and determine whether once-daily regimens
      based on this principle will have a lasting role in clinical practice.

PMID- 12802761
TI  - Exercise and vitamin E intake are independently associated with metabolic
      abnormalities in human immunodeficiency virus-positive subjects: a cross
      sectional study.
AB  - We investigated the relationship among habitual exercise, diet, and the presence
      of metabolic abnormalities (body fat redistribution, dyslipidemia, and insulin
      resistance) in a cross-sectional study of 120 human immunodeficiency virus (HIV)
      infected subjects with use of bivariate and multivariate regression-analysis
      models. Total and aerobic exercise were significantly and negatively associated
      with fasting plasma triglyceride levels in the entire sample and in the fat
      redistribution group. Inverse associations between total or aerobic exercise and
      insulin resistance were suggestive but did not achieve statistical significance.
      Diastolic blood pressure was significantly and inversely associated with
      supplemental or total but not habitual dietary intake of vitamin E. In
      conclusion, exercise and vitamin E intake were independently and negatively
      associated with several phenotypic manifestations of HIV-associated metabolic
      syndrome, whereas other macro- or micronutrients did not have comparable
      significance.

PMID- 12802762
TI  - Isolated antibody to hepatitis B core antigen in human immunodeficiency virus
      type-1-infected individuals.
AB  - We screened 651 human immunodeficiency virus (HIV)-1-infected subjects for
      hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen
      (anti-HBs). Of a total of 387 subjects who tested negative for both HBsAg and
      anti-HBs, 142 underwent further testing for isolated presence of antibody to
      hepatitis B core antigen (anti-HBc). Of these 142 subjects, 60 (42%) tested
      positive for anti-HBc (isolated anti-HBc). Individuals coinfected with HIV-1 and
      hepatitis C virus (HCV) were more likely to have isolated anti-HBc than were
      subjects with HIV-1 alone (80% vs. 16%, respectively). Our findings suggest that
      individuals with HIV-1/HCV coinfection for whom there is no serological evidence
      for hepatitis B virus when screened with HBsAg and anti-HBs will be positive for
      anti-HBc in >75% of cases. A screening strategy that tests only for HBsAg and
      anti-HBs in HIV-1-infected patients will miss a large number of individuals with
      isolated anti-HBc.

PMID- 12802763
TI  - Vancomycin-intermediate Staphylococcus aureus with phenotypic susceptibility to
      methicillin in a patient with recurrent bacteremia.
AB  - Vancomycin-intermediate Staphylococcus aureus (VISA) are an emerging problem. We
      observed a statistically significant inverse relationship in the MICs of
      vancomycin and oxacillin in S. aureus isolates from a patient undergoing
      hemodialysis who received 26 weeks of treatment with vancomycin during November
      1999 through April 2000. All isolates were mecA positive and were
      indistinguishable by pulsed-field gel electrophoresis. The evolving
      susceptibility patterns of this strain highlight the challenges of detecting and
      treating VISA infections.

PMID- 12802764
TI  - The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic
      fever in Iran.
AB  - We compared the mortality rate among patients suspected of having Crimean-Congo
      hemorrhagic fever (CCHF) who received treatment with oral ribavirin and those who
      did not. Ninety-seven (69.8%) of 139 treated patients suspected of having CCHF
      survived, and 61 (88.9%) of 69 treated patients with confirmed CCHF survived. The
      efficacy of oral ribavirin was 80% among patients with confirmed CCHF and 34%
      among patients suspected of having CCHF. Considering the limitations of
      observational studies, we conclude that oral ribavirin is an effective treatment
      for the hemorrhagic form of CCHF.

PMID- 12802765
TI  - Successful treatment of coccidioidal meningitis with voriconazole.
AB  - A previously healthy 47-year-old man with coccidioidal meningitis had fluconazole
      treatment failure and developed severe symptoms, multiple cranial nerve palsies,
      and brain-stem inflammation visible on magnetic resonance imaging (MRI). High
      dose voriconazole therapy resulted in gradual resolution of almost all signs and
      symptoms, normalization of cerebrospinal fluid, and clearing of brain-stem edema
      seen on MRI. The patient had photosensitivity after 10 weeks of treatment, but
      this improved when the voriconazole dose was lowered. Continuous voriconazole
      therapy kept coccidioidal meningitis in complete remission in this patient for >2
      years.

PMID- 12802766
TI  - Serious thrombocytopenia due to dengue hemorrhagic fever treated with high
      dosages of immunoglobulin.

PMID- 12802767
TI  - Prevalence and optimal detection of C. upsaliensis in stool specimens.

PMID- 12802769
TI  - Dedicated catheter lumens for parenteral nutrition.

PMID- 12802771
TI  - Safety evaluations of drugs containing artemisinin derivatives for the treatment
      of malaria.

PMID- 12802773
TI  - Reiter's syndrome as a manifestation of an immune reconstitution syndrome in an
      HIV-infected patient: successful treatment with doxycycline.

PMID- 12802774
TI  - Unilateral brachial plexopathy associated with West Nile virus
      meningoencephalitis.

PMID- 12802775
TI  - Treatment recommendations for bacterial vaginosis in pregnant women.

PMID- 12802777
TI  - Very rapid evolution of infection with hepatitis C virus transmitted by an
      accidental needlestick.

PMID- 12802778
TI  - No evidence for a major risk of roseolovirus vertical transmission during
      pregnancy.

PMID- 12802779
TI  - Incidence of multidrug-resistant tuberculosis in urban and rural India and
      implications for prevention.
AB  - We compared the incidence of multidrug resistance in 150 consecutive
      Mycobacterium tuberculosis isolates obtained from a rural center (in Sakawar,
      India) and an urban tertiary care center (in Mumbai, India). The study highlights
      an alarmingly high percentage of multidrug-resistant M. tuberculosis isolates in
      Mumbai (51%) as compared with that at the rural center (2%).

PMID- 12802780
TI  - Severe community-acquired pneumonia with acute hypoxemic respiratory failure due
      to primary infection with Chlamydia pneumoniae in a previously healthy adult.
AB  - Community-acquired pneumonia due to Chlamydia pneumoniae is associated with a
      benign clinical course. Severe, life-threatening pneumonia is rare and occurs
      only in immunocompromised hosts. We report a case of severe pneumonia complicated
      by acute hypoxemic respiratory failure due to primary infection with C.
      pneumoniae in a previously healthy 46-year-old woman.

PMID- 12802781
TI  - Severe hepatotoxicity associated with rifampin-pyrazinamide preventative therapy
      requiring transplantation in an individual at low risk for hepatotoxicity.
AB  - We report a case of severe hepatotoxicity associated with rifampin-pyrazinamide
      preventative therapy that required liver transplantation in a closely monitored,
      human immunodeficiency virus-uninfected individual who had no risk for
      hepatotoxicity. Because hepatotoxicity associated with this treatment appears to
      be idiosyncratic, we recommend closer monitoring of liver enzyme levels than do
      the Centers for Disease Control and Prevention guidelines, as well as at least
      temporary interruption of treatment during any elevation of liver enzyme levels
      greater than the normal value.

PMID- 12802782
TI  - Human immunodeficiency virus infection with human granulocytic ehrlichiosis
      complicated by symptomatic lactic acidosis.
AB  - Lactic acidosis has been reported as a complication associated with
      antiretroviral therapy; in particular, usually with use of nucleoside reverse
      transcriptase inhibitors. We describe a human immunodeficiency virus (HIV)
      infected patient with a history of lipodystrophy who presented with hepatic
      insult associated with documented human granulocytic ehrlichiosis (HGE). Despite
      a normal serum lactate level before the onset of acute coinfection, the patient
      developed symptomatic hyperlactatemia while receiving appropriate treatment for
      HGE. To date, this is the first presentation of symptomatic hyperlactatemia in a
      patient with HIV infection and HGE.

PMID- 12802783
TI  - Haplotype block partition with limited resources and applications to human
      chromosome 21 haplotype data.
AB  - Recent studies have shown that the human genome has a haplotype block structure
      such that it can be decomposed into large blocks with high linkage disequilibrium
      (LD) and relatively limited haplotype diversity, separated by short regions of
      low LD. One of the practical implications of this observation is that only a
      small fraction of all the single-nucleotide polymorphisms (SNPs) (referred as
      "tag SNPs") can be chosen for mapping genes responsible for human complex
      diseases, which can significantly reduce genotyping effort, without much loss of
      power. Algorithms have been developed to partition haplotypes into blocks with
      the minimum number of tag SNPs for an entire chromosome. In practice,
      investigators may have limited resources, and only a certain number of SNPs can
      be genotyped. In the present article, we first formulate this problem as finding
      a block partition with a fixed number of tag SNPs that can cover the maximal
      percentage of the whole genome, and we then develop two dynamic programming
      algorithms to solve this problem. The algorithms are sufficiently flexible to
      permit knowledge of functional polymorphisms to be considered. We apply the
      algorithms to a data set of SNPs on human chromosome 21, combining the
      information of coding and noncoding regions. We study the density of SNPs in
      intergenic regions, introns, and exons, and we find that the SNP density in
      intergenic regions is similar to that in introns and is higher than that in
      exons, results that are consistent with previous studies. We also calculate the
      distribution of block break points in intergenic regions, genes, exons, and
      coding regions and do not find any significant differences.

PMID- 12802784
TI  - A haplotype implicated in schizophrenia susceptibility is associated with reduced
      COMT expression in human brain.
AB  - The gene encoding catechol-O-methyltransferase (COMT) is a strong candidate for
      schizophrenia susceptibility, owing to the role of COMT in dopamine metabolism,
      and the location of the gene within the deleted region in velocardiofacial
      syndrome, a disorder associated with high rates of schizophrenia. Recently, a
      highly significant association was reported between schizophrenia and a COMT
      haplotype in a large case-control sample (Shifman et al. 2002). In addition to a
      functional valine-->methionine (Val/Met) polymorphism, this haplotype included
      two noncoding single-nucleotide polymorphisms (SNPs) at either end of the COMT
      gene. Given the role of COMT in dopamine catabolism and that deletion of 22q11
      (containing COMT) is associated with schizophrenia, we postulated that the
      susceptibility COMT haplotype is associated with low COMT expression. To test
      this hypothesis, we have applied quantitative measures of allele-specific
      expression using mRNA from human brain. We demonstrate that COMT is subject to
      allelic differences in expression in human brain and that the COMT haplotype
      implicated in schizophrenia (Shifman et al. 2002) is associated with lower
      expression of COMT mRNA. We also show that the 3' flanking region SNP that gave
      greatest evidence for association with schizophrenia in that study is transcribed
      in human brain and exhibits significant differences in allelic expression, with
      lower relative expression of the associated allele. Our results indicate that
      COMT variants other than the Val/Met change are of functional importance in human
      brain and that the haplotype implicated in schizophrenia susceptibility is likely
      to exert its effect, directly or indirectly, by down-regulating COMT expression.

PMID- 12802787
TI  - Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: Methods
      and power analysis.
AB  - This is the first of three articles on a meta-analysis of genome scans of
      schizophrenia (SCZ) and bipolar disorder (BPD) that uses the rank-based genome
      scan meta-analysis (GSMA) method. Here we used simulation to determine the power
      of GSMA to detect linkage and to identify thresholds of significance. We
      simulated replicates resembling the SCZ data set (20 scans; 1,208 pedigrees) and
      two BPD data sets using very narrow (9 scans; 347 pedigrees) and narrow (14
      scans; 512 pedigrees) diagnoses. Samples were approximated by sets of affected
      sibling pairs with incomplete parental data. Genotypes were simulated and
      nonparametric linkage (NPL) scores computed for 20 180-cM chromosomes, each
      containing six 30-cM bins, with three markers/bin (or two, for some scans).
      Genomes contained 0, 1, 5, or 10 linked loci, and we assumed relative risk to
      siblings (lambda(sibs)) values of 1.15, 1.2, 1.3, or 1.4. For each replicate,
      bins were ranked within-study by maximum NPL scores, and the ranks were averaged
      (R(avg)) across scans. Analyses were repeated with weighted ranks
      ((sqrt)N[genotyped cases] for each scan). Two P values were determined for each
      R(avg): P(AvgRnk) (the pointwise probability) and P(ord) (the probability, given
      the bin's place in the order of average ranks). GSMA detected linkage with power
      comparable to or greater than the underlying NPL scores. Weighting for sample
      size increased power. When no genomewide significant P values were observed, the
      presence of linkage could be inferred from the number of bins with nominally
      significant P(AvgRnk), P(ord), or (most powerfully) both. The results suggest
      that GSMA can detect linkage across multiple genome scans.

PMID- 12802789
TI  - The interaction of thymidylate synthase expression with p53-regulated signaling
      pathways in tumor cells.
AB  - Thymidylate synthase (TS) is a chemotherapeutic target for the fluoropyrimidine 5
      fluorouracil (5-FU) and antifolate tomudex (TDX). Using the MCF-7 breast cancer
      line, we have developed a cell line with inducible TS expression termed M7TS90.
      Inducible TS expression in this line resulted in a moderate (approximately 3
      fold) increase in 5-FU 50% inhibitory concentration at 72 hours (IC-50(72 h))
      dose and a dramatic (approximately 24-fold) increase in the IC-50(72 h) dose of
      TDX, but did not affect chemosensitivity to cisplatin, oxaliplatin, irinotecan,
      and paclitaxel. In the absence of drug treatment, inducible TS expression had no
      effect on expression of the p53 tumor suppressor gene. However, TS induction
      abrogated p53, p21, Fas, and Bak induction in response to TDX, but not 5-FU.
      Similarly, downregulation of Bcl-2 was reversed by inducible TS expression in
      TDX, but not 5-FU-treated cells. Our results indicate that inducible TS
      expression in M7TS90 cells modulates p53 and p53 target gene expression in
      response to TDX, but not 5-FU.

PMID- 12802790
TI  - Cyclooxygenase-2 inhibitors in colorectal cancer.
AB  - Cyclooxygenase (COX) enzyme-dependent arachidonic acid metabolites occupy key
      positions in important physiologic processes such as immunity, reproduction, and
      vascular integrity. Large retrospective and prospective population-based studies
      have shown that the use of both nonselective, nonsteroidal anti-inflammatory
      drugs and selective COX-2 inhibitors are associated with decreased colorectal
      cancer incidence and mortality rate. A majority of animal studies provide strong
      evidence that prevention of intestinal tumors is more efficiently accomplished by
      COX-2 selective inhibition rather than by COX-1 suppression. The inducible COX-2
      isoform is overexpressed in colorectal tissues and is associated with critical
      events of tumorigenesis. COX-2 expression correlates with expression of
      angiogenic factors and new blood vessel formation. Inhibition of COX-2 favors
      apoptosis and causes a dose-dependent decline of tumor growth and metastasis in
      these models. These data, together with the fact that COX-2 inhibitors cause less
      toxic side effects compared with nonselective nonsteroidal anti-inflammatory
      drugs, render these new compounds promising candidates in chemoprevention and
      treatment of colorectal cancer. Results from initial clinical trials suggest that
      COX-2 inhibitors may be able to reduce the polyp burden in patients with familial
      polyposis coli. However, further clinical studies are needed to evaluate whether
      COX-2 inhibition will be effective in all types of colorectal tumor tissues. This
      is especially true for neoplastic lesions that express COX-2 at a lower level
      (eg, hereditary nonpolyposis colorectal cancer) and for colorectal tumors of
      patients with inflammatory bowel disease. In summary, COX-2 inhibitors represent
      a new and very promising group of chemotherapeutic agents with great potential
      for both colorectal cancer prevention and treatment.

PMID- 12802785
TI  - Genome scan meta-analysis of schizophrenia and bipolar disorder, part III:
      Bipolar disorder.
AB  - Genome scans of bipolar disorder (BPD) have not produced consistent evidence for
      linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18
      BPD genome scan data sets in an effort to identify regions with significant
      support for linkage in the combined data. The two primary analyses considered
      available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder
      BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks
      weighted for sample size. A "broad" model (i.e., adding recurrent major
      depression) and unweighted analyses were also performed. No region achieved
      genomewide statistical significance by several simulation-based criteria. The
      most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very
      narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally
      significant P values were observed in adjacent bins on chromosomes 9p and 18p-q,
      across all three disease models on chromosomes 14q and 18p-q, and across two
      models on chromosome 8q. Relatively few BPD pedigrees have been studied under
      narrow disease models relative to the schizophrenia GSMA data set, which produced
      more significant results. There was no overlap of the highest-ranked regions for
      the two disorders. The present results for the very narrow model are promising
      but suggest that more and larger data sets are needed. Alternatively, linkage
      might be detected in certain populations or subsets of pedigrees. The narrow and
      broad data sets had considerable power, according to simulation studies, but did
      not produce more highly significant evidence for linkage. We note that meta
      analysis can sometimes provide support for linkage but cannot disprove linkage in
      any candidate region.

PMID- 12802786
TI  - Genome scan meta-analysis of schizophrenia and bipolar disorder, part II:
      Schizophrenia.
AB  - Schizophrenia is a common disorder with high heritability and a 10-fold increase
      in risk to siblings of probands. Replication has been inconsistent for reports of
      significant genetic linkage. To assess evidence for linkage across studies, rank
      based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia
      genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with
      the bins ranked by linkage scores (1 = most significant) and the ranks averaged
      across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected
      casess]). A permutation test was used to compute the probability of observing, by
      chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the
      same place (first, second, etc.) in the order of average ranks in each
      permutation (P(ord)). The GSMA produced significant genomewide evidence for
      linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage
      were also met (clusters of nominally significant P values that did not occur in
      1,000 replicates of the entire data set with no linkage present): 12 consecutive
      bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p,
      11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05,
      additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q.
      There is greater consistency of linkage results across studies than has been
      previously recognized. The results suggest that some or all of these regions
      contain loci that increase susceptibility to schizophrenia in diverse
      populations.

PMID- 12802791
TI  - Development of ZD1839 in colorectal cancer.
AB  - Colorectal cancer is one of the most frequent human malignancies. Therapeutic
      options are mainly limited to chemotherapy with 5-fluorouracil in various
      schedules or in combination with irinotecan and oxaliplatin; however, novel
      approaches are also in development. These new agents specifically attack
      molecular targets involved in tumor biology. One such target is the epidermal
      growth factor receptor (EGFR), which is highly expressed in many tumors and is
      associated with a poor prognosis. The EGFR plays a key role in cell proliferation
      and has been implicated in several processes that mediate cancer progression.
      ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor that has
      shown extensive preclinical activity and favorable tolerability in advanced
      clinical trials in a variety of tumors. In colorectal cancer cells, ZD1839 has
      shown both in vitro and in vivo antitumor activity as monotherapy or in
      combination with cytotoxic agents such as paclitaxel and irinotecan. Preclinical
      data have also shown that ZD1839 reverses resistance to irinotecan and enhances
      its efficacy by improving oral bioavailability. These studies indicate that EGFR
      inhibition by ZD1839 may have a valuable role in the treatment of colorectal
      cancer, and clinical studies in patients with colorectal cancer are ongoing.

PMID- 12802792
TI  - Development of the epidermal growth factor receptor inhibitor OSI-774.
AB  - The epidermal growth factor receptor (EGFR) is a transmembrane receptor involved
      in the regulation of a complex array of essential biological processes such as
      cell proliferation and survival. Dysregulation of the EGFR signaling network has
      been frequently reported in multiple human cancers and has been associated with
      the processes of tumor development, growth, proliferation, metastasis, and
      angiogenesis. Inhibition of the EGFR was associated with antitumor effects in
      preclinical models. On the basis of these data, therapeutics targeting the EGFR
      were explored in clinical trials. OSI-774 is a small-molecule selective inhibitor
      of the EGFR tyrosine kinase. In preclinical studies, OSI-774 inhibited the
      phosphorylation of the EGFR in a dose-dependent and concentration-dependent
      manner resulting in cell cycle arrest and induction of apoptosis. In in vivo
      studies, this agent caused tumor growth inhibition and showed synergistic effects
      when combined with conventional chemotherapy. Subsequent single-agent phase I
      studies and phase I studies in combination with chemotherapy showed that the
      agent has a good safety profile and induced tumor growth inhibition in a
      substantial number of patients with a variety of different solid tumors.
      Preliminary reports from phase II studies confirmed the excellent tolerability of
      OSI-774 and showed encouraging preliminary activity. Phase III studies have
      either been completed or are ongoing in several tumor types such as lung cancer
      and pancreatic cancer. In summary, OSI-774 is a novel inhibitor of the EGFR
      tyrosine kinase that has shown promising activity in initial studies and is
      currently undergoing full development as an anticancer drug.

PMID- 12802793
TI  - Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK
      222584.
AB  - PTK787/ZK 222584 (PTK/ZK) is an oral potent and selective inhibitor of the
      vascular endothelial growth factor (VEGF)-mediated Flt-1 and KDR receptor
      tyrosine kinases. PTK/ZK has been shown to reduce growth and microvasculature in
      subcutaneously implanted human tumor xenografts in nude mice. A clinical
      difficulty in evaluating angiogenesis inhibitors has been the usefulness of
      conventional study endpoints. Therefore, dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) has been studied as a pharmacodynamic marker of
      efficacy of PTK/ZK. Phase I studies are under way evaluating the optimum dose and
      schedule of oral PTK/ZK administered continuously to patients with advanced
      cancers of types known to overexpress VEGF. To date, particularly in patients
      with liver metastases from colorectal cancer treated with PTK/ZK, DCE-MRI has
      been a useful predictor of the biological response of VEGF-receptor inhibition.
      Toxicities have been manageable and have included lightheadedness, ataxia,
      nausea, vomiting, and hypertension. Stabilization of disease for >/= 6 months has
      been seen in heavily pretreated patients receiving PTK/ZK at higher doses.
      Preliminary data suggest that PTK/ZK can be administered safely on a continuous
      daily dosing schedule, efficacy data look promising, and DCE-MRI correlates with
      biological response. DCE-MRI will be used to guide dose optimization of PTK/ZK
      and perhaps of other angiogenesis inhibitors in future studies.

PMID- 12802794
TI  - Inhibition of vascular endothelial growth factor in the treatment of colorectal
      cancer.
AB  - Angiogenesis is essential for tumor growth and metastasis and is a promising
      target in the search for new anti-neoplastic agents. Angiogenesis is a tightly
      regulated process dependent on the complex interplay between inhibitory and
      stimulatory angiogenic factors. Vascular endothelial growth factor is one of the
      best characterized of the pro-angiogenic growth factors, and multiple strategies
      have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody
      developed against vascular endothelial growth factor, has shown initial
      preclinical and clinical activity. This review will outline the conceptual basis
      of anti-angiogenic therapy, discuss the critical role of vascular endothelial
      growth factor, and summarize the available data on the use of bevacizumab in
      colorectal cancer.

PMID- 12802795
TI  - EPO906 (epothilone B): a promising novel microtubule stabilizer.
AB  - EPO906 (epothilone B) is a potent member of a new class of microtubule
      stabilizing cytotoxic agents known as epothilones. Although structurally
      unrelated to the clinically validated taxanes, EPO906 acts similarly to promote
      the formation and stabilization of microtubules, arresting proliferating cells in
      mitosis, and eventually causing cell demise by apoptosis. In preclinical studies,
      EPO906 has shown anticancer activity both in vitro and in vivo against several
      cancer types, including models that are paclitaxel-resistant. Importantly, in
      contrast to the taxanes, EPO906 retained activity against cancer cells either
      overexpressing the P-glycoprotein efflux pump or bearing tubulin mutations. Two
      phase I studies with EPO906 were conducted to determine the safety and maximal
      tolerated dose on two different dosing schedules: weekly and every 3 weeks.
      Diarrhea was the dose-limiting toxicity on both schedules. Tumor responses were
      seen in colorectal cancer as well as a variety of other tumor types, such as
      breast, ovarian, lung, and carcinoid in these two phase I trials. Based on the
      promising results from phase I studies, phase II studies in numerous indications
      are ongoing.

PMID- 12802796
TI  - Signaling inhibition with radiation in colorectal cancer: clinical trials.
AB  - Ras has been shown to increase radiation resistance. Thus, upstream and
      downstream pathways from Ras could be targets for manipulation of
      radiosensitivity. Epidermal growth factor receptor (EGFR) expression and Akt
      phosphorylation are also associated with the response to radiation. A
      retrospective study evaluating EGFR and Akt in patients treated with
      multimodality therapy found a significant association between P-Akt and treatment
      failure. Moreover, these data are strengthened by in vitro studies showing that
      inhibition of EGFR, Ras, PI3K, and Akt radiosensitized cancer cell lines. We have
      previously shown that PI3K is a mediator of Ras-induced radiation resistance. We
      now suggest that EGFR, which is upstream of PI3K, may also mediate resistance
      through a common pathway. In addition to EGFR and Ras, PTEN can also regulate the
      PI3K pathway. Identifying a common signal for EGFR, Ras, or PTEN that results in
      radiation resistance may uncover targets for developing molecular-based
      radiosensitization protocols for tumors resistant to radiation and thus improve
      local control.

PMID- 12802797
TI  - Optimal use of the combination of irinotecan and 5-fluorouracil.
AB  - 5-Fluorouracil (5-FU) and irinotecan are now widely used for the treatment of
      advanced colorectal cancer. The drugs work by different mechanisms, and colon
      cancers do not generally manifest cross-resistance to the two agents when they
      are used serially. Most recently, combination regimens with irinotecan, 5-FU, and
      leucovorin have produced survival benefits superior to 5-FU and leucovorin. In
      Europe, irinotecan is most frequently combined with an infusion regimen of 5-FU,
      whereas in the United States bolus 5-FU has been favored until recently. The
      regimen, commonly known as IFL or the Saltz regimen, consists of irinotecan,
      bolus 5-FU, and leucovorin given weekly for 4 weeks and then repeated in 6-week
      cycles. Two intergroup trials reported a significant 60-day mortality rate with
      the IFL regimen, leading to the description of both a gastrointestinal syndrome
      and a vascular syndrome. Vigorous management of the gastrointestinal syndrome is
      now recommended. Furthermore, there are data to suggest that the infusion 5-FU
      combination with irinotecan appears to produce a similar survival advantage to
      IFL with less overall severe toxicity based on cumulative European data for
      patients with advanced colorectal cancer. Future directions include the testing
      of a complex array of new agents and the incorporation of laboratory predictors
      of survival and response as a component of clinical trial design.

PMID- 12802798
TI  - Current status of oxaliplatin in colorectal cancer.
AB  - Novel platinum compounds have been sought with the goal of identifying molecules
      active in cisplatin-resistant cancers such as colorectal cancer. Some 30 years
      ago it was shown that varying the structure of the coordination complex could
      enhance the activity of platinum compounds against preclinical models. The
      diaminocyclohexane ligand, now embodied in the structure of oxaliplatin, was the
      most promising of a series of such analogues. Oxaliplatin has recently been
      approved in the United States for the treatment of refractory colorectal cancer.
      Studies in the initial treatment of advanced disease indicate that its activity
      when used in combination with 5-fluorouracil (5-FU) is at least as good as
      standard therapy for this stage of the disease. Novel combinations have been
      reported in phase II studies, and adjuvant trials have been completed in the
      United States and Europe. It is reasonable to conclude that there are now two
      accepted regimens for the treatment of colorectal cancer, irinotecan/5-FU and
      oxaliplatin/5-FU. Early studies using both regimens sequentially are of interest,
      and phase I trials of three-drug combinations have been presented. Current
      efforts are directed toward individualizing therapy through predictive analyses
      of the targets and metabolic pathways of all three agents in pharmacogenetic and
      pharmacogenomic studies.

PMID- 12802799
TI  - Practical considerations in the use of oral fluoropyrimidines.
AB  - Since its synthesis over 40 years ago, several studies including patients with
      colorectal cancer have shown that prolonged exposure to 5-fluorouracil (5-FU) is
      associated with better antitumor activity and decreased toxicity. However, the
      use of continuous-infusion 5-FU is costly and is associated with the need for a
      catheter and infusion pump. The use of an oral formulation of 5-FU allows
      protracted exposure without the inconvenience and cost of intravenous continuous
      infusion regimens. Capecitabine is a rationally designed fluoropyrimidine that
      can be given orally and uses the high concentration of thymidine phosphorylase
      within cancer cells to concentrate heavily within the tumor. Two large randomized
      studies that included patients with metastatic colorectal cancer have shown
      superior response rates for capecitabine compared with bolus regimens of 5-FU
      with equal times to progression, overall survival, and duration of response.
      Because of its favorable toxicity profile and the efficacy shown in early trials,
      capecitabine is currently being investigated in the adjuvant setting and in
      combination with radiotherapy and with other chemotherapy agents.

PMID- 12802802
TI  - Arsenite induces delayed mutagenesis and transformation in human osteosarcoma
      cells at extremely low concentrations.
AB  - Arsenite is a human multisite carcinogen, but its mechanism of action is not
      known. We recently found that extremely low concentrations (</=0.1 microM) of
      arsenite transform human osteosarcoma TE85 (HOS) cells to anchorage-independence.
      In contrast to other carcinogens which transform these cells within days of
      exposure, almost 8 weeks of arsenite exposure are required for transformation. We
      decided to reexamine the question of arsenite mutagenicity using chronic exposure
      in a spontaneous mutagenesis assay we previously developed. Arsenite was able to
      cause a delayed increase in mutagenesis at extremely low concentrations (</=0.1
      microM) in a dose-dependent manner. The increase in mutant frequency occurred
      after almost 20 generations of growth in arsenite. Transformation required more
      than 30 generations of continuous exposure. We also found that arsenite induced
      gene amplification of the dihydrofolate reductase (DHFR) gene in a dose-dependent
      manner. Since HOS cells are able to methylate arsenite at a very low rate, it was
      possible that active metabolites such as monomethylarsonous acid (MMA(III))
      contributed to the delayed mutagenesis and transformation in these cells.
      However, when the assay was repeated with MMA(III), we found no significant
      increase in mutagenesis or transformation, suggesting that arsenite-induced
      delayed mutagenesis and transformation are not caused by arsenite's metabolites,
      but by arsenite itself. Our results suggest that long-term exposure to low
      concentrations of arsenite may affect signaling pathways that result in a
      progressive genomic instability.

PMID- 12802801
TI  - Cell-cycle deregulation in BALB/c 3T3 cells transformed by 1,2-dibromoethane and
      folpet pesticides.
AB  - The cell-transforming potential of 1,2-dibromoethane and folpet, two widely used
      agricultural pesticides that are potential sources of environmental pollution,
      has been previously ascribed to their promoting activity. In this study, we
      investigated whether BALB/c 3T3 transformation by these chemicals was associated
      with the deregulation of signals involved in cell-cycle progression and in cell
      cycle checkpoint induction. We found that two BALB/c 3T3 cell clones transformed
      by in vitro medium-term (8-week) exposure to the carcinogens had a constitutive
      acceleration of cell transition from G(1) to S phase and an abrogation of the
      radiation-induced G(1)/S checkpoint. These events involved multiple signals; in
      particular, the inhibitors of cyclin/cyclin-dependent kinase complexes p21 and
      p27 were significantly down-modulated and the positive regulators of cell-cycle
      progression cyclin D(3) and E were up-modulated. As anticipated for cells where
      the G(1)/S checkpoint was abrogated, the transformed cells exhibited a
      significant reinforcement of the radiation-induced G(2)/M checkpoint, the only
      checkpoint remaining to protect genomic integrity. However, cyclin A(1) and B(1)
      coexpression and cyclin A(1) overexpression were found despite the G2 arrest in
      irradiated cells and these signals likely attenuate the G(2)/M checkpoint. These
      alterations to normal cell cycling may promote the emergence of both numerical
      and structural chromosomal abnormalities and their tolerance. Such a condition
      could play a key role in neoplastic transformation and be crucial in tumor
      progression. Furthermore, cyclin A(1) overexpression may play an autonomous role
      in the neoplastic transformation of BALB/c 3T3 cells, as it does in other cell
      types of mesenchymal origin.

PMID- 12802803
TI  - Analysis of 8-hydroxydeoxyguanosine 5'-monophosphate (8-OH-dGMP) as a reliable
      marker of cellular oxidative DNA damage after gamma-irradiation.
AB  - In order to improve 8-hydroxyguanine (8-OH-Gua) detection in DNA, we digested
      isolated DNA with nuclease P1 and analyzed for 8-hydroxydeoxyguanosine 5'
      monophosphate (8-OH-dGMP) using a high-performance liquid chromatography system
      equipped with an electrochemical detector (HPLC-ECD). The amount of 8-OH-Gua in
      the DNA was expressed as the ratio of 8-OH-dGMP to deoxycytidine monophosphate
      (dCMP). Using this analysis, the background level of 8-OH-Gua in DNA from human
      lung carcinoma cells (A549) was several-fold lower than that obtained by a
      previous method. A549 cells were exposed to 20-60 Gy of gamma-radiation and an
      increase in 8-OH-Gua concentration was observed with increasing gamma-ray dose
      (0.3 residues per 10(7) dCMP per Gy). Moreover, by an immunohistochemical
      procedure using a commercial FITC-kit, 8-OH-Gua was clearly detected in A549
      cells and the fluorescence intensity of cells with oxidative DNA damage increased
      with the doses of gamma-irradiation. Using an endonuclease nicking assay, we also
      found that gamma-rays decreased 8-OH-Gua repair activity. The results indicate
      that 8-OH-dGMP is a useful and sensitive marker for estimating oxidative damage
      in DNA.

PMID- 12802804
TI  - Positive correlation between the frequency of micronucleated cells and dysplasia
      in Papanicolaou smears.
AB  - Most cancers arise in epithelial tissues and these tissues are typically the
      targets of the carcinogens responsible for the tumors. Exfoliated epithelial
      cells have traditionally been used for cancer screening by cytopathologists and
      these cells also can be used for biomonitoring of genotoxic effects in humans.
      Cervical cancer results from the progression of preinvasive precursor lesions,
      called low-grade squamous intraepithelial lesions (LGSILs), to high-grade
      squamous intraepithelial lesions (HGSILs). The gradient from low to high-grade
      lesions is characterized by increasing nuclear atypia and the failure of cellular
      differentiation in progressively more superficial levels of the epithelium. These
      phenotypic changes are hypothesized to be accompanied by increased genetic
      instability that can be documented using the micronucleus (MN) assay in
      exfoliated cervical cells. A retrospective study was performed to investigate the
      frequency of micronucleated cells in cervical smears from women at high risk for
      developing cervical cancer. Papanicolaou (Pap) smears from 275 women previously
      studied at a cancer clinic were coded and analyzed for the frequency of
      micronucleated cells. LGSIL, HGSIL, and invasive carcinoma smears had
      significantly higher frequencies than normal and ASCUS (abnormal squamous cells
      of undetermined origin) smears. HGSIL or severely dysplastic smears had the
      highest frequency of micronucleated cells (although not significantly higher than
      LGSIL smears), an observation that that could be useful in confirming these types
      of lesions. The results indicate that the MN frequency in exfoliated cervical
      cells may be an additional criterion for establishing cervical cancer risk.

PMID- 12802805
TI  - Altered expression of zinc finger proteins, ADAMs, and integrin-related proteins
      following treatment of cultured human cells with a low concentration of N-methyl
      N'-nitro-N-nitrosoguanidine.
AB  - Proteomic analysis is an important approach to characterize the proteome and
      study protein functions. It is also a powerful screening method for detecting
      unexpected alterations in protein expression that may be overlooked by
      conventional biochemical techniques. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      is an alkylating agent that can induce nontargeted mutagenesis in treated cells,
      although the mechanism remains unclear. Using an efficient proteomic method, we
      identified several cellular proteins that are responsive to low-concentration
      MNNG treatment in human FL cells. After MNNG treatment, whole cellular proteins
      were separated using two-dimensional gel electrophoresis and visualized by silver
      staining; the digitized images then were analyzed with 2D analysis software. More
      than 60 proteins showed significant changes in MNNG-treated cells compared to
      control cells (DMSO treatment). Thirty-one proteins only detected in MNNG-treated
      or control cells were subjected to in-gel digestion with trypsin and identified
      by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass
      spectrometry using peptide mass fingerprinting. Eighteen of theses proteins have
      been identified, including several zinc finger proteins, two members of the ADAMs
      (a disintegrin and metalloprotease domain) family, and two integrins. Most of
      these proteins have unknown functions and their involvement in the cellular
      responses to alkylating agents have not been reported. Therefore, our findings
      may offer new insights into the mechanisms of low-concentration MNNG-induced
      nontargeted mutagenesis and these proteins may serve as new biomarkers for
      detecting exposure of human populations to environmental carcinogens.

PMID- 12802806
TI  - Genotoxicity of surface water treated with different disinfectants using in situ
      plant tests.
AB  - Disinfection of surface drinking water, in particular water chlorination, results
      in many by-products with potential genotoxic and/or carcinogenic activity. In the
      present study, we evaluated the genotoxicity of surface water after treatment
      with different disinfectants by means of in situ plant genotoxicity assays
      (micronucleus and chromosomal aberration tests) which can detect both clastogenic
      and aneugenic effects. The study was carried out at a pilot plant using lake
      water after sedimentation and filtration. This water supplied four stainless
      steel basins: three basins were disinfected with sodium hypochlorite, chlorine
      dioxide, and peracetic acid and the fourth basin containing untreated lake water
      was used as a control. Plants were exposed in situ in the basins. The study was
      carried out using water collected in different seasons over a period of about 1
      year in order to assess the treatments in different physical and chemical lake
      water conditions. The micronucleus test in root cells of Vicia faba (Vicia
      faba/MCN test) revealed genotoxicity in many samples of disinfected water. The
      micronucleus test in Tradescantia pollen cells and the chromosome aberration test
      in root cells of Allium cepa showed genotoxic effects only in some disinfected
      samples, but also revealed genotoxicity in raw water. The results of the study
      indicated that the Vicia faba/MCN test was the most sensitive plant assay for
      disinfected water and that peracetic acid disinfection produced similar or lower
      genotoxicity than sodium hypochlorite or chlorine dioxide treatment.

PMID- 12802807
TI  - Mutagenicity, antioxidant potential, and antimutagenic activity against hydrogen
      peroxide of cashew (Anacardium occidentale) apple juice and cajuina.
AB  - Fresh and processed cashew (Anacardium occidentale) apple juice (CAJ) are among
      the most popular drinks in Brazil. Besides their nutritional benefits, these
      juices have antibacterial and antitumor potential. The chemical constituents of
      both the fresh juice and the processed juice (cajuina) were analyzed and
      characterized as complex mixtures containing high concentrations of vitamin C,
      various carotenoids, phenolic compounds, and metals. In the present study, these
      beverages exhibited direct and rat liver S9-mediated mutagenicity in the
      Salmonella/microsome assay with strains TA97a, TA98, and TA100, which detect
      frameshifts and base pair substitution. No mutagenicity was observed with strain
      TA102, which detects oxidative and alkylating mutagens and active forms of
      oxygen. Both CAJ and cajuina showed antioxidant activity as determined by a total
      radical-trapping potential assay. To test whether this antioxidant potential
      might result in antimutagenesis, we used a variation of the Salmonella/microsome
      assay that included pre-, co-, and posttreatment of hydrogen peroxide-exposed
      Salmonella typhimurium strain TA102 with the juices. CAJ and cajuina protected
      strain TA102 against mutation by oxidative damage in co- and posttreatments. The
      antimutagenic effects during cotreatment with hydrogen peroxide may be due to
      scavenging free radicals and complexing extracellular mutagenic compounds. The
      protective effects in posttreatment may be due to stimulation of repair and/or
      reversion of DNA damage. The results indicate that CAJ and cajuina have
      mutagenic, radical-trapping, antimutagenic, and comutagenic activity and that
      these properties can be related to the chemical constituents of the juices.

PMID- 12802808
TI  - Improvement of the Spi- assay for mutations in gpt delta mice by including
      magnesium ions during plaque formation.

PMID- 12802809
TI  - Seasonal variations in the onset of childhood leukemia/lymphoma: April 1996 to
      March 2000, Shiraz, Iran.
AB  - Infection has long been suspected as a possible factor in the aetiology of
      leukemia and lymphoma, one of the most common malignancies in children. Since
      most viral infections have seasonal variations of onset, if seasonal trends in 1
      month of diagnosis of leukemia and lymphoma could be proved, this would be
      supportive evidence for an infectious aetiology. A total of 367 cases in the
      Hospitals of Shiraz University of Medical Sciences, from April 1996 through March
      2000, who were diagnosed as having acute lymphocytic leukemia (ALL), acute
      myeloblastic leukemia (AML), Burkitt's lymphoma (BL) chronic myeloblastic
      lymphoma (CML), Hodgkin's disease (HD) or non-Burkitt's type non-Hodgkin's
      lymphoma (NBNHL) were analysed. The month of appearance of the first symptom and
      the date of diagnosis were recorded. ALL demonstrated statistically significant
      monthly variation in the date of appearance of the first symptom (p < 0.05; peak
      in October) and the date of diagnosis (p < 0.05; peak in November). Seasonal
      variation was demonstrated in the date of the first appearance of symptoms in BL
      (p < 0.042), and in the date of diagnosis in AML (p < 0.049). There was no
      statistically significant seasonal variation in the month of diagnosis for other
      groups. Analysis based on the date of the first symptoms and the date of
      diagnosis for ALL patients, using summer-winter ratios, also showed a significant
      winter excess (p < 0.001). Our data provide modest support for an autumn-winter
      peak in the diagnosis of childhood ALL, underlying mechanisms that account for
      these patterns are likely to be complex and need more definitive studies.

PMID- 12802810
TI  - Increasing incidence of non-Hodgkin's lymphoma in Canada, 1970-1996: age-period
      cohort analysis.
AB  - Previous studies have shown that the incidence of non-Hodgkin's lymphoma (NHL)
      has increased in many parts of the world in recent decades. Using data obtained
      from the Canadian Cancer Registry, the present study examined time trends in NHL
      incidence in Canada between 1970 and 1996 and the effects of age, period of
      diagnosis and birth cohort on incidence patterns for each sex separately. Results
      showed that overall age-adjusted incidence rates increased substantially, from
      7.3 and 5.2 per 100,000 in 1970-1971 to 14.0 and 10.0 per 100,000 in 1995-1996 in
      males and females, respectively. Diffuse lymphoma was the major histological
      subtype, accounting for approximately 76% of NHL cases over the 27-year period.
      The data suggest that period effects have played a major role, although birth
      cohort effects may also have been involved. Sex-specific patterns of the
      incidence were similar over the time period of diagnosis but were distinct among
      recent birth cohorts. In conclusion, there is in fact a marked increase in NHL in
      Canada which cannot be explained in terms of improvements in diagnosis, changes
      in NHL classification and the increase in AIDS-associated NHL alone. The birth
      cohort effect in NHL suggests that changes in risk factors may have contributed
      to the observed increase.

PMID- 12802811
TI  - The effects of STI571 on antigen presentation of dendritic cells generated from
      patients with chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia is caused by the acquisition of the reciprocal
      (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion
      protein showed higher and aberrant tyrosine kinase activity. The inhibition of
      the tyrosine kinase activity of the protein represents a specific therapeutic
      strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2
      phenylaminopyrimidine class that selectively inhibits the tyrosine kinase
      activity of the Abl protein tyrosine kinase. In this study, we evaluated the
      effects of STI571 on antigen presentation of dendritic cells generated from the
      patients with CML. The data showed that by the addition of STI571 the dendritic
      cells derived from CML clone showed an increased expression of CD1a, CD83, CD80
      and CD86 by flow cytometry analysis and showed more intense abilities of
      allogeneic antigen presentation by mixed leukocyte culture, compared with the
      control cells without STI571. Our results suggested that STI571 not only has a
      direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect
      effect associated with increased anti-leukemic immunological function due to an
      intensified antigen presentation.

PMID- 12802812
TI  - Chylous effusions complicating lymphoma: a serious event with octreotide as a
      treatment option.
AB  - Chylous effusions have an identical appearance to milk and occur when the
      thoracic duct is blocked. Since chyle represents direct absorption of fat from
      the small intestine lacteals, it is rich in fat, calories, vitamins and
      immunoglobulins. Drainage of this milk-like fluid from any cavity (chest or
      abdomen) results in rapid weight loss and profound cachexia. The recognition of
      this milk-like fluid as chyle is urgent for the implementation of the correct
      treatment. In adults, lymphoma is one of the commonest malignancies to cause
      blockages in the thoracic duct. Once the diagnosis is made, conservative
      treatment with strict dietary adjustment often fails to prevent weight loss or
      resolve the underlying cause. Since the condition is uncommon, no guidelines
      exist. Many surgeons recommend early surgical intervention before the patient
      becomes too weak. Surgery may also fail. We report the case of a 62-year-old man
      with chylous effusions and a weight loss of 30 kg. The nature of the effusion was
      unrecognized for the first 16 weeks. Upon diagnosis, dietary adjustment was made
      and a lymphangiogram organized with a view to surgery. Literature searches
      revealed two cases in which somatostatin was used after surgical procedures
      failed. We therefore used octreotide (a synthetic analogue of somatostatin). We
      report complete resolution of the condition within 72 h leading to the resumption
      of a normal diet and discharge within 2 weeks.

PMID- 12802813
TI  - Psychosomatic liaison service in hematological oncology: need for
      psychotherapeutic interventions and their realization.
AB  - Empirical investigations examining the psychosocial distress and need for care of
      inpatients with hematological malignancies are rare. Little is known about the
      use of psychotherapeutic interventions in routine care. To evaluate the
      psychosocial distress of hemato-oncological inpatients, the need for
      psychotherapeutic interventions and their realization in the framework of a
      psychosomatic liaison service has been assessed. Seventy-two patients from two
      hematological oncology wards underwent psychodiagnostic interviews and completed
      self-rating instruments, elucidating mental disorders, psychosocial distress,
      coping strategies, quality of life, treatment motivation and psychotherapeutic
      interventions. Using ICD-10 criteria, mental and behavioural disorders were
      diagnosed in 53% of patients. Professional assessment indicated a need for
      psychotherapeutic treatment in 49%, while 38% of the patients wished to receive
      psychological support. Actual intervention occurred for all patients in the bone
      marrow transplantation unit and for 23% of patients in the general hemato
      oncological ward. There is considerable need for psychotherapeutic treatment
      which can only be handled within the framework of a liaison service in close
      cooperation with oncologists, nurses and mental health specialists.

PMID- 12802814
TI  - Power calculations for large multi-arm placebo-controlled studies of dichotomous
      outcomes.
AB  - Several statistical methods can be used to test for differences in placebo
      controlled dichotomous multi-arm studies. These tests include linear and
      quadratic trends, Dunnett's test, Hochberg's test, and the overall chi-square
      test. We computed the power of these tests under a wide variety of alternatives.
      For two arms versus a control, the power was computed exactly. For more than two
      arms, the power was calculated from 100000 simulations per alternative. Against
      monotonic alternatives, the linear trend test tended to be superior. Against
      convex alternatives, the quadratic trend test tended to be superior. Against
      general alternatives, Dunnett's test, Hochberg's test, and the overall chi-square
      test were superior and had very similar power curves. The Hochberg test was
      generally less powerful than Dunnett's test but the difference was offset by its
      increased power to reject multiple hypotheses. These results remained nearly
      constant over a wide range of sample sizes, average event rates and average
      effect sizes.

PMID- 12802815
TI  - Assessing the appropriateness of combining economic data from multinational
      clinical trials.
AB  - Because of the potential for large variability among countries in the utilization
      and cost of health care resources, it is important to assess the appropriateness
      of combining economic data across the countries in a multinational clinical
      economic trial. We show how available tests for interaction can be applied to
      economic endpoints, including cost-effectiveness ratios and net health benefits.
      This analysis includes a characterization of possible interactions being
      quantitative or qualitative in nature. In the absence of interaction, a pooled
      estimate of the economic endpoint should be representative of the participating
      countries. We explore the analytic issues by further analysing data from the
      Scandinavian Simvastatin Survival Study (4S).

PMID- 12802816
TI  - Confidence intervals for the 50 per cent response dose.
AB  - Confidence intervals for the 50 per cent response dose are usually computed using
      either the Delta method or Fieller's procedure. Recently, confidence intervals
      computed by inverting the asymptotic likelihood ratio test have also been
      recommended. There is some controversy as to which of these methods should be
      used. By means of an extensive simulation study we examine these methods as well
      as confidence intervals obtained by the approximate bootstrap confidence (ABC)
      procedure and an adjusted form of the likelihood ratio based confidence
      intervals.

PMID- 12802817
TI  - Implications of genetic traits on vaccine efficacy.
AB  - Literature on genetic screening in the community suggests that people having
      specific genotypes may either get or protect from infection, for example,
      malaria, human papilloma virus, and haemophilic influenza, for which vaccines are
      either already developed or being targeted. In such a situation, the evaluation
      of the efficacy of vaccine in the community needs to be examined with caution. In
      this paper, I present a method for the estimation of vaccine efficacy (VE) in the
      presence of genetic traits/component (theta) and the sample size required to
      estimate the 95 per cent CI with a given relative width for the estimated vaccine
      efficacy. Considering true efficacy ranging from 40 to 80 per cent and the
      possible values of the genetic component (theta) ranging from 0 to 60 per cent,
      the VE was estimated. The 95 per cent confidence intervals (CI) for the estimated
      VE for relative widths (R) 1.0 and 0.1 were computed. The sample sizes required
      for each of the unvaccinated and vaccinated cohorts were computed for estimating
      the 95 per cent CI for given incidence rates in the unvaccinated (Iu) cohort. In
      the presence of genetic traits I found that the VE was consistently
      overestimated. There existed change in the location as well as the asymmetry of
      the 95 per cent CIs over the point estimate of VE. The sample size required for
      estimating 95 per cent CI of VE was substantially reduced, resulting in savings.
      The more the genetic component (theta) affecting disease in the community, the
      more the savings in sample size. I examined the above estimators for (i) VE, (ii)
      95 per cent CI for VE and (iii) sample size required for estimating 95 per cent
      CI of VE using the real-life data from the Haemophilus influenzae type b vaccine
      trial conducted in Finland and the global genetic structure of encapsulated H.
      influenza. Because of escalated VE and large savings in sample size for
      estimating the 95 per cent CI for VE, I recommend that the design should consider
      the genetic component that causes/protects from infection/disease for the
      evaluation of efficacy of vaccine in the field.

PMID- 12802818
TI  - Comparing HLA antigen frequencies between two groups of patients.
AB  - For diseases that involve the immune system, the alleles of the human leukocyte
      antigen (HLA) complex can play a major role. For example, if responsiveness to
      therapy is immunologically mediated, one would think that responders and non
      responders might tend to have different HLA alleles. However, comparing the
      frequencies between the two groups of patients at each allele can introduce a
      substantial multiple comparisons problem as the number of alleles is large. This
      paper proposes an efficient two-stage procedure for identifying alleles that may
      mediate response. In the first-stage, the distribution of all alleles for the
      patients are compared to a reference population and a few alleles are selected.
      These candidate alleles are then compared between the two groups of patients
      using a modest Bonferroni correction. The two-stage procedure strongly controls
      the type I error rate as the first-stage selection is statistically independent
      of the second-stage tests. We analyse a cohort of patients with bone marrow
      failure who are classified as responders or non-responders to immunosuppressive
      therapy. Published in 2003 by John Wiley & Sons, Ltd.

PMID- 12802819
TI  - A probability model for the meiosis I non-disjunction fraction in numerical
      chromosomal anomalies.
AB  - Numerical chromosome abnormalities (aneuploidies) are among the most common known
      causes of mental retardation and the leading cause of pregnancy loss in humans.
      They primarily arise by the process of meiotic non-disjunction. We still know
      very little about the contribution of genetic and environmental causes for non
      disjunction in humans. In order to increase our understanding of the epidemiology
      of human trisomies, it is necessary to establish the proportion of cases
      occurring in the first or second division of meiosis. Trisomic patients will
      display, in study of microsatellite typed by the polymerase chain reaction (PCR),
      three fragment peaks of equal intensity, two fragments at an average 2:1 dosage
      or one individual fragment. In this work we describe a statistical approach for
      estimation of the fraction of meiosis I non-disjunctions (F) in the absence of
      the parental information. First we determine a probability model for the number
      of peaks in a polymorphic microsatellite locus, which is a function of F. Based
      on this model, we obtain a maximum likelihood estimator for F, using the observed
      proportion of one, two and three allele patterns in trisomic individuals. Relying
      on the properties of maximum likelihood theory, we also calculate the asymptotic
      variance and confidence intervals for F. Owing to the fact that the samples of
      trisomic patients are limited in number, the use of asymptotic theory may be
      compromised. Thus, we employ the bootstrap technique to build confidence
      intervals for F and compare the results with those obtained from the normal
      theory. This estimator that dispenses the need to study parents opens the
      possibility of using archival material for comparative epidemiological studies of
      Down's syndrome and other aneuploidies. In this paper we propose a probability
      model to estimate the fraction of meiosis I non-disjunction, F, by only using the
      proportion of allele patterns of trisomy individuals, while traditional methods
      require typing pericentromeric markers from those affected and their parents.

PMID- 12802820
TI  - REML and ML estimation for clustered grouped survival data.
AB  - Clustered grouped survival data arise naturally in clinical medicine and
      biological research. For example, in a randomized clinical trial, the variable of
      interest is the time to occurrence of a certain event with or without a new
      treatment and the data are collected from possibly correlated subjects from
      independent clusters. However it is sometimes impossible or too expensive to
      monitor the experimental subjects continuously. The subjects are examined
      regularly and the continuous survival data are thus grouped into a discrete time
      scale. With such a design, researchers are mainly interested in the effectiveness
      of the new treatment as well as the correlation among subjects from the same
      cluster, namely the intracluster correlation. This paper suggests a random
      effects approach to the estimation of the regression parameter with various
      choices of regression model and also the dependence parameter which characterizes
      the intracluster correlation. Time dependent covariates can be accommodated in
      the proposed model, and the estimation procedure will not be further complicated
      with large cluster sizes. The proposed method is applied to the data from the
      Diabetic Retinopathy Study, the objective of which is to evaluate the
      effectiveness of laser photocoagulation in delaying or preventing the onset of
      blindness in the left and right eyes of individuals with diabetes-associated
      retinopathy. The intracluster correlation using a grouped proportional hazards
      regression model can be estimated and the relationship between the regression
      parameter estimates based on the random effects approach and the marginal
      approach using a dynamic logistic regression model are discussed. Results from a
      simulation study of the proposed method are also presented.

PMID- 12802821
TI  - Bias correction of two-state latent Markov process parameter estimates under
      misclassification.
AB  - A discretely observed two-state process may misclassify the state of an
      unobservable continuous-time, two-state Markov process. We examine the behaviour
      of maximum likelihood transition probability estimates as functions of known
      misclassification probabilities. Since maximum likelihood estimators are not
      available in closed form, we provide two alternatives for bias-adjusted
      estimation. In the case of large samples, the asymptotic bias is quantified and
      estimators are constructed iteratively using transition counts and specified
      misclassification probabilities. For finite samples, we provide an approximation
      based on partial derivatives. Estimators that are bias-adjusted to a first
      approximation are easily constructed and may serve well when misclassification
      probabilities are known to be small. Simulation studies reveal the effect of
      misclassification on estimation. Repeated diagnostic testing data illustrate the
      approaches.

PMID- 12802822
TI  - Comparing longitudinal binary outcomes in an observational oral health study.
AB  - Observational studies continue to be recognized as viable alternatives to
      randomized trials when making treatment group comparisons, in spite of drawbacks
      due mainly to selection bias. Sample selection models have been proposed in the
      economics literature, and more recently in the medical literature, as a method to
      adjust for selection bias due to observed and unobserved confounders in
      observational studies. Application of these models has been limited to cross
      sectional observational data and to outcomes that are continuous in nature. In
      this paper we extend application of these models to include longitudinal studies
      and binary outcomes. We apply a two-stage probit model using GEE to account for
      correlated longitudinal binary chewing difficulty outcomes. Chewing difficulty
      was measured every six months during a 24-month period between two groups of
      subjects: those either receiving or not receiving dental care. Dental care use
      was measured at six-month intervals as well. Results from our proposed model are
      compared to results using a standard GEE model that ignores the potential
      selection bias introduced by unobserved confounders. In this application,
      accounting for selection bias made a major difference in the substantive
      conclusions about the outcomes of interest. This is due in part to an adverse
      selection phenomenon in which those most in need of treatment (and consequently
      most likely to benefit from it) are actually the ones least likely to seek
      treatment. Our application of sample selection models to binary longitudinal
      observational outcome data should serve as impetus for increased utilization of
      this promising set of models to other health outcomes studies.

PMID- 12802823
TI  - Confidence limits for the ratio of two rates based on likelihood scores: non
      iterative method.
AB  - This paper describes a method for creating a confidence interval for the ratio of
      rates using the score statistic. This non-iterative and easy to apply procedure
      produces confidence intervals that are suitable for use with Poisson data and
      simulation results indicate that it is close to the nominal level for a wide
      range of scenarios.

PMID- 12802824
TI  - Confidence limits for the ratio of two rates based on likelihood scores: non
      iterative method.

PMID- 12802825
TI  - The fight against HIV/AIDS: opportunities and challenges.

PMID- 12802827
TI  - Low absolute CD4 counts in Ethiopians.
AB  - The CD4+ T-lymphocyte count is a widely used marker of HIV disease progression.
      The marker also plays a crucial role in determining therapeutic interventions in
      HIV infections, especially with the initiation and monitoring of antiretroviral
      therapy and prophylactic treatment for opportunistic infections. In general,
      immunological studies done thus far on adult Ethiopians revealed that, healthy
      HIV-negative Ethiopians exhibit significantly decreased values for absolute CD4
      counts than other populations. However, it remains to be illucidated whether
      Ethiopian AIDS patients develop opportunistic infections at much lower CD4 values
      than AIDS patients from Western countries, and whether Ethiopian HIV infected
      patients progress to AIDS more rapidly. Thus, establishing locally appropriate
      standard CD4 values is important in order to implement certain prophylactic or
      therapeutic interventions in our setting. Most of these studies are reported on
      international journals, which are hardly accessible to the Ethiopian
      medical/scientific community. The aim of this mini-review is, therefore, to
      provide the local scientific community and clinicians with the available
      information.

PMID- 12802826
TI  - HIV-1 seroprevalence and subtypes in police recruits from Afar regional state,
      Ethiopia.
AB  - Surveillance for HIV-1 prevalence and subtypes in Afar Region, Ethiopia was
      performed among police recruits in the year 2000, by unlinked anonymous testing.
      Of 408 samples tested, 26 (6.4%) appeared positive for HIV-1 antibodies. There
      was a trend for higher HIV-1 seroprevalence in women (9.5%, 9/95) than men (5.4%,
      17/313), which was significant in one of the 5 administrative areas: Zone 4 (p =
      0.01). Around the principal transportation route connecting Addis Ababa to the
      harbor of Djibouti there was a significantly (p = 0.03) higher HIV-1
      seroprevalence of 12.7% (14/110) than elsewhere in Afar Region. In addition, 13
      (34%) of the 29 administrative sub-areas (woredas) of Afar Region delivered HIV-1
      positive police recruits. Prevalence of syphilis antibodies was 7.4% (30/408),
      increasing by age, correlating with HIV-1 positive serology (p = 0.001) and with
      23.3% (7/30) active cases. Of 22 specimens sequenced, 12 had gp120 V3 regions
      from Ethiopian subtype C, 9 subtype C' and 1 subtype A. In conclusion, even in
      very remote areas in Ethiopia, such as Afar Region, the HIV-1 epidemic is
      established, being primarily of subtype C. Regular HIV-1 surveillances will be
      necessary to guide action to prevent further spread in this vulnerable area.

PMID- 12802828
TI  - Delayed clearance of Plasmodium falciparum in patients with human
      immunodeficiency virus co-infection treated with artemisinin.
AB  - We investigated the effect of artemisinin on the rate of clearance of Plasmodium
      falciparum in patients with or without human immunodeficiency virus (HIV) co
      infection. Initial mean (+/- SEM) parasite density was not different between HIV
      infected and HIV-uninfected groups (27,486 +/- 2,643 versus 32,892 +/- 6,583,
      respectively; P = 0.55). The mean (+/- SEM) time to clear 75% and 90% of the
      parasites was 23.1 hr +/- 1.8 and 29.3 hr +/- 1.9, respectively, for the HIV
      seropositive patients compared with 16.0 hr +/- 1.4 and 20.8 hr +/- 1.4,
      respectively for the HIV seronegative patients (P = 0.0075 and 0.0026,
      respectively). By 32 hr, almost all (6/7) HIV positive patients remained
      parasitemic in contrast with 2/12 HIV seronegative patients. Moreover, the mean
      parasite density was almost 12-fold higher in the HIV seropositive patients than
      in the HIV seronegative patients at the same period (1789 +/- 616 versus 150 +/-
      118, respectively; P = 0.0037). Overall, the mean parasite clearance time was
      37.7 hr +/- 2.1 in the HIV seropositive group and 30.0 hr +/- 2.1 in those who
      were HIV seronegative (P = 0.0284). Whereas mean fever clearance time was 40.6 hr
      +/- 2.4 for the HIV seropositive group, it was 28.7 hr +/- 1.2 for those who were
      HIV seronegative (P = 0.0001). These observations are compatible with the
      hypothesis that the host's immunity affects the activity of antimalarial drugs,
      and our data suggest for the first time that clearance of P. falciparum after
      administration of artemisinin is delayed in patients with HIV co-infection.

PMID- 12802829
TI  - Evaluation of rapid assays for screening and confirming HIV-1 infection in
      Ethiopia.
AB  - To evaluate a simple and rapid testing strategy to diagnose HIV infection in
      Ethiopia, we subjected a panel of 688 sera with known HIV serologic status
      (confirmed by ELISA/WB or double ELISA) to 3 rapid assays: Determine HIV-1/2,
      Capillus HIV-1/2 and Serocard HIV. Samples were obtained from participants in a
      cohort study on HIV-infection (72%), from tuberculosis patients (18%) and from
      participants in surveillance studies among police recruits and commercial sex
      workers (10%). The panel consisted of 249 HIV-1 positive samples, of which 68
      were HIV-1 subtype C and 1 HIV-1 subtype A, and 439 HIV-1 negative samples.
      Determine and Capillus were 100% sensitive and 99.8% specific, Serocard was 100%
      sensitive and specific. On retrospective evaluation, both parallel (samples
      tested simultaneously by two rapid assays) and serial (samples tested by two
      consecutive rapid assays) testing algorithms were 100% sensitive and specific
      when compared to ELISA/WB or double ELISA testing strategy. In conclusion rapid
      assays have high sensitivity and specificity. HIV serodiagnosis based on rapid
      assays may therefore be a valuable alternative in voluntary counselling and
      testing centres and in facilities where sophisticated laboratories are not
      available.

PMID- 12802830
TI  - Leishmaniases and HIV/AIDS co-infections: review of common features and
      management experiences.
AB  - The visceral and the different spectrum of cutaneous leishmaniases have been
      incriminated to be among the opportunistic infections co-existing with HIV/AIDS.
      In co-infections, leishmaniases surface in high prevalence, present frequently
      atypically, pose difficulties to be detected by routine diagnostic tests, most
      often result in an unfavorable response to treatment, frequent relapses and in
      premature deaths. Such presentations and management difficulties shall be
      highlighted in this review. To extract information on the scope of manifestations
      and responses to management, literature was surveyed utilizing the Pub Med
      electronic literature search. In due course, pertinent characteristics surfacing
      in HIV/AIDS and leishmaniasis co-infections comprising of clinical presentations
      and parasitological and serological findings were tracked. Investigation options,
      management approaches, outcomes of various treatment regimen and other
      intervention strategies were as well explored. Visceral leishmaniasis and HIV-1
      are both associated with a depression of T cell response and similar disturbances
      of cytokine networks. The appearance of HIV has led to numerous atypical clinical
      manifestations of leishmaniasis among immunocompromised patients to include,
      recurrences, lingual, cervical, esophageal, mucocutaneous and presentations in
      other unusual sites. The common clinical presentations of the disease might not
      always be present being masked by other associated opportunistic infections.
      Spleen aspiration is more sensitive in immuno-competent visceral visceral
      leishmaniasis suspects, however, bone marrow aspirate remains the safest and the
      most frequently employed diagnostic technique in co-infected patients. Several
      species of Leishmania are incriminated in affecting HIV infected subjects,
      including formerly unknown zymodemes. In spite of the high number of reported
      cases of HIV-related VL, the treatment of choice, the best dosage and the
      duration of therapy appear not to be properly established. The pentavalent
      antimonials still remain the first line of therapy for co-infected cases.
      Amphotericin-B, especially the liposome formulation (Ambisome) was found to be
      relatively less toxic and more potent compared to pentamidine. A broad spectrum
      of other drugs have as well been used. The widespread use of HAART are envisaged
      to contribute to a progressive decrease in the morbidity and mortality of HIV
      associated visceral leishmaniasis. There is no effective chemoprophylaxis or
      immuno-prophylaxis to prevent leishmanial infection. In the events of co
      infections with HIV/AIDS, the need for policy provisions to control both diseases
      needs to be underlined. It is as well of a paramount importance that factors
      influencing co-infection are understood for effective treatment against
      leishmaniasis in co-infected patients. The need for improved diagnostic tests and
      new more effective and less toxic drugs is also apparent.

PMID- 12802831
TI  - Antiretroviral therapy and resistance to antiretroviral drugs.
AB  - Slightly more than a decade after the discovery of HIV as the causative agent of
      AIDS, effective therapies against this virus have become available. Because of a
      large degree of cross-resistance among antiretroviral agents in the same class
      (nRTIs, NNRTIs, or PIs), once a therapy has failed virologically, future
      therapeutic options with currently available drugs are limited, however. Poor
      tolerability and toxicity may also compromise the long-term prospects of
      antiretroviral therapy. Nevertheless, benefits of antiretroviral therapy far
      outweigh the downsides and efforts to scale up responsible use of antiretroviral
      agents in developing countries are a priority in the fight against HIV/AIDS. This
      paper presents an overview of antiretroviral therapy and resistance to
      antiretroviral drugs.

PMID- 12802832
TI  - Building capacity for cardiovascular nursing research in Canada.

PMID- 12802833
TI  - Connecting for Health researching with community.

PMID- 12802834
TI  - The uncertain journey: women's experiences following a myocardial infarction.
AB  - Current literature indicates that women, and society in general, do not see
      coronary heart disease (CHD) as a serious concern for women. This lack of
      recognition seems, in part, to be related to a lack of research involving women
      as participants and in developing nursing knowledge specific to women and CHD.
      Although existing literature provides valuable insight into cardiac recovery, it
      does not clearly explore women's perceptions of their experiences in the early
      home convalescent recovery process following a myocardial infarction (MI). This
      study reports on the supportive-educative experiences of eight English speaking
      women, ages 33-61, in their early recovery process following an MI. Inductively
      generated data analysis has provided a means to understand the process of
      recovery from the perspective of these participants. Inherent in the
      participants' words, as they discussed their journeys with recovery, was an
      overwhelming sense of uncertainty while living with heart disease. For these
      women, their socially constructed knowledge dictated that women, and in
      particular, young women, did not experience heart attacks, and was, therefore, in
      conflict with their realities. The contradiction between the 'truths learned from
      others' and their MI experiences influenced, and was influenced by, the
      subsequent emerging themes of a 'rude awakening,' 'disconnected knowing,' and
      'reconnecting self.' Feminist research challenges tradition and offers nursing an
      opportunity to explore and investigate issues of importance to our profession in
      a different way. Nurses, as well as other health care professionals, need to be
      aware of the social construction of cardiac illness and women's experiences, as
      this knowledge has great implications for patient care from prevention to
      rehabilitation within the cardiac experience. Based on the results of this study,
      implications for nursing education, research and practice are discussed.

PMID- 12802835
TI  - White coat hypertension in treated hypertensives: a three year follow-up study.
AB  - Patients who participated in an initial study in a hypertension outpatient clinic
      in a tertiary care hospital in Western Canada were approached three years later
      to participate in a follow-up study. The aim of this study was to describe
      changes, over three years, in office (OBP) and ambulatory blood pressure and
      blood pressure load (BPL) in a group of treated hypertensives, with and without
      white coat hypertension (WCH). In the initial study, 103 consecutive patients
      with OBP over 140/90 (either/both), despite being prescribed two or more
      antihypertensive drugs, were divided into groups based on average daytime
      ambulatory blood pressures (DABP). Sustained hypertension was defined as DABP >
      140/90 (both) and WCH as DABP < 135/85 (both). All others were defined as
      borderline hypertension. In 1998, we repeated office and DABP readings in 79 of
      the original 103 patients. Daytime BPL decreased significantly over the three
      years of the study for those originally categorized as sustained hypertension [78
      + 21 to 50 + 34 for systolic BPL (p = < 0.001) and 75 + 21 to 41 + 29 for
      diastolic BPL (p = < 0.001)]. Similarly, BPL fell in borderline hypertensives
      while BPL remained low, but increased somewhat, for WCH. OBP declined in all
      groups; thus, from a medical standpoint, this supports the argument that all
      those diagnosed with hypertension based on the OBP should remain on
      antihypertensive treatment. For nurses counselling patients with WCH, it provides
      a cautionary note that these patients, if already on antihypertensive medication,
      should probably continue treatment as WCH does not appear to be stable over time.

PMID- 12802836
TI  - Heart failure: an overview of consensus guidelines and nursing implications.
AB  - Heart failure affects more than 350,000 Canadians and costs over $1 billion
      annually for inpatient care alone. Consensus guidelines have been developed to
      guide care and improve quality of life based on current evidence or best
      practice. This article will provide a brief overview of medications and lifestyle
      modifications described in guidelines developed by the American College of
      Cardiology/American Heart Association, the Canadian Cardiovascular Society, the
      Heart Failure Society of America, and the European Society of Cardiology.
      Medications for treating heart failure can be divided into two groups: those with
      a mortality benefit (angiotensin converting enzyme inhibitor, beta-blockers, and
      selective aldosterone receptor antagonists), and those that improve symptoms
      (diuretics and cardiac glycosides). Nursing implications include careful
      assessment of volume status, vital signs, monitoring electrolyte and renal
      function, as well as spacing of medications. Nurses play a key role in assisting
      patients to identify their lifestyle habits that require modifications,
      ultimately improving their quality of life and decreasing hospital readmissions.
      Education focusing on self-care activities, diet, rest, and exercise enables
      patients to retain a sense of control in their lives.

PMID- 12802837
TI  - Self-administered cardiac medication program evaluation.
AB  - For patients to manage their medication regimens at home, adequate preparation is
      required prior to hospital discharge. Self-administered medication programs are a
      strategy for improving medication knowledge and regimen adherence. The purpose of
      this study was to evaluate the effectiveness of a self-administered cardiac
      medication program on patients knowledge of and adherence to their medication
      regimen. Patient and nurse satisfaction with the self-administered medication
      program were assessed. A comparison group, repeated measures design was used in
      which patients received nurse-administered medications (n = 172) or self
      administered medications (n = 178). Data were collected at admission, discharge,
      and 2, 6, and 16 weeks post-discharge. Outcome variables were medication
      knowledge, medication adherence, and program satisfaction. Patients in the self
      administered medication group had significantly higher medication knowledge
      scores over time compared to those in the nurse-administered medication group.
      There was no statistically significant difference between groups on medication
      adherence. The self-administered medication group reported significantly higher
      levels of satisfaction and had significantly fewer medication errors and
      medication-related problems compared to the nurse-administered medication group.

PMID- 12802838
TI  - Publishing your findings.
AB  - The road to publication often seems complicated for newer authors. Therefore, in
      this column, the authors will clarify the publication process. Topics including
      why publication is important, choosing a journal, preparing the manuscript-as
      well as some tips for writing and understanding and responding to peer review-are
      addressed.

PMID- 12802839
TI  - Effects of chlordiazepoxide (Librium) during pregnancy and lactation.
AB  - The decision to use psychotropic drugs during pregnancy and lactation must depend
      upon considerations of teratogenicity, effects on fetal and neonatal behavior and
      development, and a concern for the health and safety of the mother. Pregnancy
      itself can exacerbate anxiety symptoms, as well as alter the pharmacokinetics of
      antianxiety drugs; it thus presents a special problem to the clinician treating
      anxiety disorder in women. Since almost all psychotropic drugs cross the
      placenta, the use of medications during pregnancy and lactation requires critical
      attention to the timing of exposure, dosage, duration of use, and fetal
      susceptibility. Risk to the mother and fetus can be reduced with a number of
      simple strategies, including monotherapy with the lowest effective, multiple dose
      of a drug for the shortest period necessary and avoidance of exposure to
      Benzodiazepines (BZDs) during the first trimester, since this is when the
      developing fetus is most vulnerable to the toxic effects of most agents. This
      literature review highlights information from various sources regarding risks for
      pregnant and lactating mothers to long acting BZDs, especially Chlordiazepoxide.

PMID- 12802840
TI  - Progressive multifocal leukoencephalopathy in a patient with chronic myelogenous
      leukemia.
AB  - A 42-year-old man with chronic myelogenous leukemia presented to the hospital
      with hip pain. After undergoing surgical repair for a hip fracture, he developed
      aphasia, facial droop and fever. He was initially diagnosed with a stroke. A
      lumbar puncture excluded common infections, and an ELISA test for HIV was
      negative. Serial MRI scans revealed a progressive demyelinating pattern.
      Polymerase chain reaction performed on cerebrospinal fluid was positive for the
      JC virus (JC are the initials of the first person diagnosed with this virus). The
      patient was treated with cidofovir but died before a full course could be
      administered. JC virus is present in most adult hosts but is only harmful in
      immuno-compromised hosts. The active form of the disease is known as progressive
      multifocal leukoencephalopathy. This is the first reported case of a patient
      developing progressive multifocal leukoencephalopathy. with chronic myelogenous
      leukemia as the only underlying condition.

PMID- 12802841
TI  - Role of pharmacodynamics in designing dosage regimens for beta-lactams.

PMID- 12802842
TI  - Three new drugs for hyperlipidemia.

PMID- 12802843
TI  - Are living wills useful? In search of a new paradigm.
AB  - Living wills are written by patients to direct physicians and loved ones as to
      the medical care they want in the event of catastrophic illness that is
      accompanied by inability to communicate their wishes. We outline recent data
      suggesting that living wills are poorly understood by patients who have them and
      that the usefulness of these documents in the clinical arena is extremely
      limited. Potential solutions for current deficiencies in end-of-life care and
      decision-making are discussed.

PMID- 12802844
TI  - Mark Twain and his family's health: Livy Clemens' neurasthenia in the gilded age
      and chronic fatigue syndrome of today.
AB  - Our purpose is to compare and contrast the 19th century diagnosis and disease
      neurasthenia with the contemporary illness known as Chronic Fatigue Syndrome. The
      health of Mark Twain's wife, Olivia (Livy) Clemens, will then be discussed and
      evaluated with respect to these two medical conditions.

PMID- 12802845
TI  - A letter to the parents of a patient whose name I have forgotten.

PMID- 12802846
TI  - Legislators, involvement, and PACs.

PMID- 12802847
TI  - The structure of DNA: a fiftieth birthday.

PMID- 12802848
TI  - Qualidigm conducts health care quality improvement activities in Connecticut.

PMID- 12802849
TI  - Re: Hemorrhagic angiomyolipoma and tuberous sclerosis complex: a case report.
      Recognizing the needs of a growing population of adults with tuberous sclerosis
      complex.

PMID- 12802850
TI  - Destructive forces.

PMID- 12802851
TI  - Nursing and respite care services for ventilator-assisted children.
AB  - Home care for children requiring life-sustaining technological interventions has
      become an increasingly common alternative to long-term hospitalization since the
      1970s. The Ventilator Assisted Children's Home Program, a state-funded program in
      the Commonwealth of Pennsylvania, has provided services to more than 600 infants
      and children requiring mechanical ventilation and their families. Under this
      program, children have the opportunity to live at home with their families and
      receive quality medical care. However, over time, parents and nurses have
      acknowledged that this care can often be stressful and overwhelming. Nursing and
      respite care services in the home environment can provide these families with
      extremely valuable supports.

PMID- 12802852
TI  - Searching for the heart of home care. The Bayada Way Project.

PMID- 12802853
TI  - Lighting the way: improving the way children die in America.
AB  - The death of an infant or child is a special sorrow, leaving a devastating and
      enduring impact that demands of us the very best we can offer to prevent and
      relieve suffering--for the child as well as the family. Pediatric end-of-life
      care is very different from adult palliative and hospice care and thus requires
      specialized knowledge and training to address the unique needs of these patients.
      In the wake of a recent Institute of Medicine (IOM) report on palliative and end
      of-life care for children, there is a momentous opportunity to shed light on the
      scarcity of palliative and hospice care services for infants and children. A new
      coalition of pediatric hospice and palliative care leaders has been formed to
      serve as a unified voice for the leaders in the field, and the parents and
      children with which they work. This article examines the work of the coalition,
      the unique nature of pediatric end-of-life care, and the opportunities to effect
      change afforded by the release of the IOM report.

PMID- 12802854
TI  - Pediatric end-of-life care: coming of age?
AB  - In the United States alone, 75,000-100,000 children die each year, and an
      additional one million are seriously ill with progressive medical conditions.
      However, very few end-of-life programs target children's special needs.
      Introducing support and palliative care early into a child's final journey is key
      to alleviating distress for both child and parent. This article reviews several
      programs which tackle the difficult issue of pediatric end-of-life care.

PMID- 12802855
TI  - A tribute to Pedro Jose "Joe" Greer: physician to the poor. Interview by Val J
      Halamandaris.

PMID- 12802856
TI  - A tribute to Edward L. Schneider. Interview by Val J. Halamandaris.

PMID- 12802858
TI  - Bill to provide respite for caregivers introduced.

PMID- 12802857
TI  - Motivating yourself and others.

PMID- 12802859
TI  - Marketing pediatric specialty programs.

PMID- 12802860
TI  - Helping patients avoid repeat hospital admissions.

PMID- 12802861
TI  - Pediatric care: the next frontier of home care.

PMID- 12802862
TI  - Outside in. Award-winning designs integrate natural elements.

PMID- 12802863
TI  - City living seniors. The summit: a contemporary campus for modern-minded elderly.

PMID- 12802864
TI  - Free to be. A barrier-free design makes residents at home indoors and out.

PMID- 12802865
TI  - It takes a village. The Waveny Care Center brings back classic small town feel.

PMID- 12802866
TI  - A context for wellness. Old world charm arrives in modern Dallas through
      Edgemere.

PMID- 12802867
TI  - Over the bridge ... nothing beats old fashioned, mother nature-like therapy.

PMID- 12802868
TI  - Common interests. Innovation is the key for these winning renovation projects.

PMID- 12802869
TI  - Mood music. When it comes to helping residents experience the joy of music,
      nothing beats a live show.

PMID- 12802870
TI  - The evolution of sex differences in spatial ability.
AB  - It is widely believed that male mammals have better spatial ability than females.
      A large number of evolutionary hypotheses have been proposed to explain these
      differences, but few species have been tested. The authors critically review the
      proposed evolutionary explanations for sex differences in spatial cognition and
      conclude that most of the hypotheses are either logically flawed or, as yet, have
      no substantial support. Few of the data exclusively support or exclude any
      current hypotheses. The hypothesis with the strongest support proposes that range
      size was the selection pressure that acted to increase spatial ability. The
      authors suggest ways in which these hypotheses could be tested by presenting
      explicit predictions and suggesting suitable test species or conditions.

PMID- 12802871
TI  - Olfactory and/or visual cues for spatial navigation through ontogeny: olfactory
      cues enable the use of visual cues.
AB  - This study analyzed the spatial memory capacities of rats in darkness with visual
      and/or olfactory cues through ontogeny. Tests were conducted with the homing
      board, where rats had to find the correct escape hole. Four age groups (24 days,
      48 days, 3-6 months, and 12 months) were trained in 3 conditions: (a) 3 identical
      light cues; (b) 5 different olfactory cues; and (c) both types of cues, followed
      by removal of the olfactory cues. Results indicate that immature rats first take
      into account olfactory information but are unable to orient with only the help of
      discrete visual cues. Olfaction enables the use of visual information by 48-day
      old rats. Visual information predominantly supports spatial cognition in adult
      and 12-month-old rats. Results point out cooperation between vision and olfaction
      for place navigation during ontogeny in rats.

PMID- 12802872
TI  - Differential involvement of nucleus accumbens shell and core subregions in
      maternal memory in postpartum female rats.
AB  - Maternal memory refers to the long-term retention of maternal responsiveness as a
      consequence of animals' prior experiences with their young. This study examined
      the relative roles of 2 subregions of the nucleus accumbens (NA; shell and core)
      in maternal memory in rats. NA shell lesions either before or immediately after a
      short experience significantly disrupted maternal memory, but lesions after a 24
      hr maternal experience had no effect. NA core lesions had no significant impact
      on maternal memory. Cycloheximide (a protein synthesis inhibitor) at a high dose
      (25 micrograms/microliter) infused in the NA shell immediately after 1 hr of
      maternal experience also significantly disrupted maternal memory, whereas
      infusions in the medial preoptic area had no effect. It was concluded that the NA
      shell, but not the NA core, is involved in the consolidation of maternal memory.

PMID- 12802873
TI  - Establishment of a preference by the newborn lamb for its mother: the role of
      opioids.
AB  - Mother-young relationships in sheep are characterized by individual recognition
      and a rapidly developing exclusive bond. The authors examined the role of opioids
      in establishment of the lamb's preference for its mother. Newborn lambs received
      the opioid receptor antagonist naltrexone (0.0, 1.5, or 3.0 mg/kg i.p.), and
      lambs were tested at 24 hr and 48 hr of age. At 24 hr, controls spent
      significantly more time near the mother than near an alien ewe; no significant
      difference was obtained for the naltrexone-treated groups. The effect of
      naltrexone persisted at 48 hr. No other significant behavioral difference was
      observed. Results support the hypothesis that opioids mediate the establishment
      of mother preference and the view that positive affect associated with social
      attachment and maternal care may be modulated by opioids.

PMID- 12802874
TI  - Vasopressin and the transmission of paternal behavior across generations in
      mated, cross-fostered Peromyscus mice.
AB  - The role of arginine vasopressin (AVP) in the nongenomic transfer of paternal
      behavior from fathers to offspring was examined in Peromyscus. Male California
      mice (P. californicus) exposed to fewer retrievals by white-footed mouse (P.
      leucopus) foster parents displayed fewer retrievals of biological offspring. In
      contrast, white-footed mice were retrieved equally rarely by California mouse
      foster parents and by biological parents and displayed no changes in pup
      retrieval behavior. AVP-immunoreactive staining in the bed nucleus of the stria
      terminalis may predict paternal behavior because it correlated positively with
      retrievals and with a score consisting of huddling, grooming, and time inside the
      nest. The authors discuss AVP as a possible mechanism by which early experience
      shapes adult paternal behavior.

PMID- 12802875
TI  - SEE locomotor behavior test discriminates C57BL/6J and DBA/2J mouse inbred
      strains across laboratories and protocol conditions.
AB  - Conventional tests of behavioral phenotyping frequently have difficulties
      differentiating certain genotypes and replicating these differences across
      laboratories and protocol conditions. This study explores the hypothesis that
      automated tests can be designed to quantify ethologically relevant behavior
      patterns that more readily characterize heritable and replicable phenotypes. It
      used SEE (Strategy for the Exploration of Exploration) to phenotype the locomotor
      behavior of the C57BL/6 and DBA/2 mouse inbred strains across 3 laboratories. The
      2 genotypes differed in 15 different measures of behavior, none of which had a
      significant genotype-laboratory interaction. Within the same laboratory, most of
      these differences were replicated in additional experiments despite the test
      photoperiod phase being changed and saline being injected. Results suggest that
      well-designed tests may considerably enhance replicability across laboratories.

PMID- 12802876
TI  - Short-term beta-amyloid vaccinations do not improve cognitive performance in
      cognitively impaired APP + PS1 mice.
AB  - Prior work demonstrated that beta-amyloid (A beta) immunotherapy for 8 months
      prevented cognitive impairment in 16-month-old APP + PS1 transgenic mice. In the
      present study, 4 immunizations administered biweekly to cognitively impaired 16
      month-old transgenic mice could not reverse deficits in working memory or
      reference memory in the radial arm water maze or in visual platform recognition,
      possibly because of inadequate antibody exposure. Nontransgenic mice showed
      cognitive savings between the 16- and 18-month test periods, but the transgenic
      groups did not. These results suggest that a longer period of active
      immunotherapy, or passive immunization, may be required to provide sufficient
      antibody titers to improve cognition in older transgenic mice. A beta-based
      immunotherapy for Alzheimer's disease will likely be more successful
      prophylactically than therapeutically.

PMID- 12802877
TI  - Age-related deficits in mice performing working memory tasks in a water maze.
AB  - This study determined whether mice exhibit spatial working memory deficits with
      increased age. C57BL/6JNia mice of 3 different ages were tested in the Morris
      water maze with 2 protocols designed to assess immediate and delayed working
      memory abilities. Young mice required multiple trials in order to show
      improvements in the working memory task. Deficits in immediate working memory
      were detected in both 10- and 24- to 26-month-old mice. Reference memory deficits
      and declines in performance in the delayed working memory task were only seen in
      24- to 26-month-olds. This increased susceptibility of immediate working memory
      processes to the aging process in mice may be related to their need for more
      rehearsal in the water maze than other species.

PMID- 12802878
TI  - Wheel access duration in rats: I. Effects on feeding and running.
AB  - The effects of 0-, 2-, and 24-hr wheel access on the pattern of running, feeding,
      and weight were explored over 24 days in 3 groups of 8 male rats. Both 2 and 24
      hr of wheel access suppressed feeding by about 15% for about 8 days before
      feeding gradually returned to normal. Weight in these 2 groups was similar and
      was suppressed for the 24 days. Like the pattern seen with drug self
      administration (S. H. Ahmed & G. F. Koob, 1998, 1999), running levels stayed low
      with short, 2-hr daytime wheel access, but with long, 24-hr access, rats' running
      escalated over days to chronically high levels. These results may have relevance
      for the understanding of addiction and anorexia nervosa.

PMID- 12802879
TI  - Cortisol variation in humans affects memory for emotionally laden and neutral
      information.
AB  - In a test of the effects of cortisol on emotional memory, 90 men were orally
      administered placebo or 20 or 40 mg cortisol and presented with emotionally
      arousing and neutral stimuli. On memory tests administered within 1 hr of
      stimulus presentation, cortisol elevations caused a reduction in the number of
      errors committed on free-recall tasks. Two evenings later, when cortisol levels
      were no longer manipulated, inverted-U quadratic trends were found for
      recognition memory tasks, reflecting memory facilitation in the 20-mg group for
      both negative and neutral information. Results suggest that the effects of
      cortisol on memory do not differ substantially for emotional and neutral
      information. The study provides evidence of beneficial effects of acute cortisol
      elevations on explicit memory in humans.

PMID- 12802880
TI  - Selective effects of triazolam on memory for emotional, relative to neutral,
      stimuli: differential effects on gist versus detail.
AB  - Benzodiazepines are known to reduce learning and memory performance, presumably
      through their facilitation of GABAergic neurotransmission, but the effects of
      these drugs specifically on memory for emotional material has not been addressed
      in humans. The effects of a benzodiazepine (triazolam, 0.25 mg) on nonincidental
      memory for emotional stimuli were assessed in 20 healthy volunteers (10 female).
      Triazolam reduced the normally facilitative effect of emotion on memory. The drug
      specifically affected memory for the gist of stimuli while leaving detail memory
      relatively unaffected. This pattern of performance is similar to that seen in
      patients with amygdala damage. Results suggest an effect of GABAergic
      neurotransmission at the level of the amygdala on memory modulation.

PMID- 12802881
TI  - Scopolamine impairs human recognition memory: data and modeling.
AB  - Eight subjects studied a set of complex visual images after administration of 0.4
      mg scopolamine. Another 8 subjects performed the same task without drug
      administration. On a subsequent item recognition test, subjects rated, on a 5
      point scale, their confidence that the studied pictures and an equal number of
      unstudied lures were actually presented. Results showed that scopolamine affected
      responses to studied items, but not unstudied lures, demonstrating an unambiguous
      effect of scopolamine on recognition memory. To describe the scopolamine-injected
      subjects' data, the authors constructed a new model of 2-process recognition that
      includes the A. P. Yonelinas (1994) model as a limiting case. The model analysis
      suggests that scopolamine affected both familiarity and recollection. In
      particular, scopolamine did not affect the frequency with which recollection took
      place, but rather, affected the amount of recollected information.

PMID- 12802882
TI  - Regional brain variations of cytochrome oxidase staining during olfactory
      learning in the honeybee (Apis mellifera).
AB  - Regional brain variations of cytochrome oxidase (CO) staining were analyzed in
      the honeybee (Apis mellifera) after olfactory conditioning of the proboscis
      extension reflex. Identification of brain sites where stimuli converge was done
      by precise image analysis performed in antennal lobes (AL) and mushroom bodies
      (MB). In Experiment 1, bees received 5 odorant stimulations that induced a
      transient decrease of CO activity in the lateral part of the AL. In Experiment 2,
      bees were trained with 5-trial olfactory conditioning. CO activity transiently
      increased in the lips of the MB calyces. There was also a delayed increase in the
      lateral part of the AL. An olfactory stimulus presented alone and an odor paired
      to a sucrose stimulation are treated by different pathways, including both AL and
      MB.

PMID- 12802883
TI  - The role of telencephalic NMDA receptors in avoidance learning in goldfish
      (Carassius auratus).
AB  - Studies with goldfish (Carassius auratus) have suggested that N-methyl-D
      aspartate (NMDA) receptors are concentrated most densely in the telencephalon, a
      simple structure homologous to the limbic structure of higher vertebrates. The
      present study investigated the amnestic effects of microinjections of the NMDA
      receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) to the
      goldfish telencephalon on avoidance conditioning. Results showed that
      microinjections of D-AP5 before training impaired avoidance learning at doses
      that did not impair performance processes. High-performance liquid chromatography
      measurements showed that D-AP5 was detected only in the telencephalon following
      microinjections. Thus, D-AP5 impaired avoidance learning through its interaction
      with telencephalic NMDA receptors in goldfish. Furthermore, microinjections of D
      AP5 to the goldfish telencephalon immediately following training did not impair
      memory consolidation of avoidance conditioning.

PMID- 12802884
TI  - Temporal and spatial aspects of an environmental stimulus influence the dynamics
      of behavioral regulation of the Aplysia siphon-withdrawal response.
AB  - Exposure to turbulence, an environmental stimulus, produces behavioral adaptation
      in the Aplysia siphon-withdrawal response (SWR). The authors show that the
      duration and spatial extent of turbulence influence adaptation recovery. In terms
      of duration, recovery in whole animals and reduced preparations (tail, siphon,
      and CNS) was more rapid after longer exposures to turbulence (10 min) than after
      briefer exposures (10 s-5 min). In terms of spatial extent, recovery in reduced
      preparations was more rapid after diffuse turbulence (tail and siphon together)
      compared with focal turbulence (siphon alone). Furthermore, spatial extent and
      duration interact: Duration regulates recovery only when turbulence is diffuse.
      Results suggest that SWR adaptation reflects a composite of cellular processes,
      including short-term synaptic enhancement in L30 inhibitory interneurons.

PMID- 12802885
TI  - Role of the anterior cingulate cortex in the control over behavior by Pavlovian
      conditioned stimuli in rats.
AB  - To investigate the contribution of the anterior cingulate cortex (ACC) to
      stimulus-reward learning, rats with lesions of peri- and postgenual ACC were
      tested on a variety of Pavlovian conditioning tasks. Lesioned rats learned to
      approach a food alcove during a stimulus predicting food, and responded normally
      for conditioned reinforcement. They also exhibited normal conditioned freezing
      and Pavlovian-instrumental transfer, yet were impaired at autoshaping. To resolve
      this apparent discrepancy, a further task was developed in which approach to the
      food alcove was under the control of 2 stimuli, only 1 of which was followed by
      reward. Lesioned rats were impaired, approaching during both stimuli. It is
      suggested that the ACC is not critical for stimulus-reward learning per se, but
      is required to discriminate multiple stimuli on the basis of their association
      with reward.

PMID- 12802886
TI  - Entorhinal cortex lesions disrupt the transition between the use of intra- and
      extramaze cues for navigation in the water maze.
AB  - This study with rats examined the effects of excitotoxic lesions to the
      entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze
      cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a
      disruption to the use of extramaze cues, but not intramaze cues, whereas EC
      lesions had no effect on the use of these cues when they were encountered for the
      first time. However, prior navigation training in which 1 type of cue was
      relevant disrupted navigation with the other type in rats with EC lesions.
      Results show that the EC contributes to the processing of spatial information,
      but that this contribution is most apparent when there is a conflict between 2
      sources of navigational cues in the water maze.

PMID- 12802887
TI  - Impairment of radial maze delayed nonmatching after lesions of anterior thalamus
      and parahippocampal cortex.
AB  - This study compared the effects of lesions damaging hippocampus-related pathways
      in anterior thalamus (AT) and parahippocampal (PH) cortex on allocentric spatial
      memory. Rats were trained to perform radial maze delayed nonmatching (DNM) with
      random selection of arms to prevent egocentric solutions. After experimental
      treatment (control, excitotoxic AT, radiofrequency PH, or combined AT-PH
      lesions), rats were retrained for 30 sessions from 2 to 8 weeks after surgery.
      Results showed comparable impairments for AT and PH lesions that added without
      interaction in the combined AT-PH group. During chronic recovery, the AT-PH group
      exhibited delay-dependent deficits comparable to previous results for hippocampal
      lesions. Thus, AT and PH lesions appear to have separate effects that together
      disrupt hippocampus-dependent spatial memory.

PMID- 12802889
TI  - Odor tracking in rats with orbital frontal lesions.
AB  - Rats track self-, conspecific, and artificial odors to locate food. The orbital
      frontal cortex has been implicated in olfactory behavior, but whether it plays a
      role in a species-typical behavior, such as odor-guided navigation, has not been
      studied. Rats were trained to track 1 of 3 different odors deposited on a string.
      After rats were reliably tracking a scented string, they received a series of 2-
      and 3-odor discrimination tests. Next, all the rats received bilateral aspiration
      lesions of the orbital frontal cortex and experienced the same sequence of tasks.
      Rats learned to track and discriminate between different odors reliably. These
      results suggest that other areas of the brain mediate odor-guided navigation
      following damage to the orbital frontal cortex.

PMID- 12802888
TI  - Gustatory thalamus lesions eliminate successive negative contrast in rats:
      evidence against a memory deficit.
AB  - Successive negative contrast is the exaggerated reduction of licking that occurs
      when rats expecting a high-value reward are given a low-value reward. This effect
      is typically investigated with a 24-hr retention interval between access periods.
      The present experiment tested the hypothesis that the absence of successive
      negative contrast in rats with bilateral lesions of the gustatory thalamus (GT)
      is due to a memory deficit. The results argue against this hypothesis by showing
      that, irrespective of retention-interval duration (7.5 min, 15 min, 45 min, 180
      min, or 24 hr), lesioned rats failed to show successive negative contrast. As
      such, the data are consistent with the alternative view that GT lesions
      specifically disrupt the reward comparison mechanism that underlies successive
      negative contrast.

PMID- 12802890
TI  - Novel objects in a holeboard probe the role of the locus coeruleus in curiosity:
      support for two modes of attention in the rat.
AB  - Idazoxan, an alpha 2 adrenoceptor antagonist (2 mg/kg), enhanced novel object
      investigation in a holeboard in rats as previously reported (V. Devauges & S. J.
      Sara, 1990). Two weeks of 10 min/day in 37 degrees C water increased dopamine
      beta-hydroxylase staining density in the locus coeruleus but did not enhance
      novel object investigation. In contrast to idazoxan, however, the warm water
      treatment increased rearing, center entries, and activity, a pattern previously
      described during tonic infusion of norepinephrine into the hippocampus.
      Correlations among dopamine-beta-hydroxylase measures and behavior reinforced
      these tonic norepinephrine/behavior associations. The behavioral effects across
      the idazoxan and warm water experiments support G. Aston-Jones et al.'s (1999) 2
      modes of attention hypothesis for locus coeruleus function: Phasic locus
      coeruleus activity promotes focused attention; tonic locus coeruleus activity
      promotes scanning attention.

PMID- 12802891
TI  - Kindling-induced emotional behavior in male and female rats.
AB  - Modeling fear in animals is a critical approach for identifying the neural
      mechanisms involved in human disorders such as generalized anxiety and panic.
      Amygdala kindling has proven useful in this regard because it produces dramatic
      increases in fearful behavior. The purpose of this experiment was to compare the
      behavioral effects of kindling in male and female rats. Compared with the sham
      stimulated rats, the kindled male and female rats showed similar increases in
      fearful behavior, with some sex differences in fear-related open-field activity.
      They also showed decreased immobility in the forced-swim test and increased
      sucrose consumption. These results suggest that kindling-induced fear is
      generally similar in male and female rats and that kindling does not appear to
      induce depression-like behavior.

PMID- 12802893
TI  - Effects of hippocampal lesions in overshadowing and blocking procedures.
AB  - The effects of ibotenic acid lesions of the hippocampus on overshadowing and
      blocking were examined in a Pavlovian appetitive conditioning experiment with
      rats. In a standard test of performance to the overshadowed or blocked target
      stimulus, sham-lesioned rats displayed both of these stimulus-selection
      phenomena. Rats with hippocampal lesions showed normal blocking, but no
      overshadowing. Subsequent inhibitory learning about the target stimulus was
      slower after overshadowing or blocking procedures than after a control procedure
      in sham-lesioned rats, but not in lesioned rats. These results suggest that
      exposure to these procedures can induce hippocampally mediated losses in
      conditioned stimulus associability (learning rate parameter), even when those
      losses are not a major determinant of the stimulus-selection effects themselves.

PMID- 12802892
TI  - Bivalent effects of MK-801 on ethanol-induced sensitization do not parallel its
      effects on ethanol-induced tolerance.
AB  - The relationship between the effects of the N-methyl-D-aspartate (NMDA)
      antagonist MK-801 on acute responses to ethanol and its ability to block ethanol
      sensitization and tolerance was examined in DBA/2J mice. Cross-sensitization
      between these drugs was also studied. Repeated administration of 0.1 mg/kg MK-801
      with ethanol potentiated, whereas 0.25 mg/kg attenuated, sensitization to
      ethanol's locomotor stimulant effects; rearing was similarly affected. There was
      evidence for cross-sensitization between ethanol and 0.25 mg/kg MK-801. MK-801
      potentiated ethanol's ataxic effects in the grid test, but had no effect on
      tolerance to this effect. MK-801's effects on ethanol sensitization appeared to
      be related to its own behavioral effects, rather than NMDA receptor blockade per
      se. Further, these studies demonstrate dissociation between ethanol sensitization
      and tolerance.

PMID- 12802894
TI  - [The neuroblastoma, "enfant terrible" among pediatric tumors].
AB  - Neuroblastoma belongs to the group of small blue round cell tumors and originates
      in precursor cells of the sympathetic neural tissue. This tumor occurs at the
      pediatric age and has fascinated and intrigued both clinicians and researchers
      because of its variable and often unpredictable clinical behaviour. Indeed, the
      clinical outcome of neuroblastoma patients not only depends on the clinical
      extension of the disease, but also on other factors including age at diagnosis,
      presence or absence in the tumor cells of molecular and biological
      characteristics with prognostic value (e.g. amplification of the oncogene MYCN,
      frequently associated with chromosome 1p-deletion is predictive for poor survival
      chance). In 1983 an abdominal stage 3 neuroblastoma was diagnosed in a 9-months
      old boy. He died of the disease 3 years later. Karyotyping studies in this
      patient revealed a constitutional chromosome translocation t(1;17) with a
      breakpoint involving the terminal part of the chromosome 1p arm. We hypothesized
      that this patient was predisposed to the development of neuroblastoma because he
      carried in all his somatic cells a chromosomal abnormality involving the region
      frequently deleted in neuroblastoma tumor cells. We assumed that the chromosomal
      translocation breakpoints might indicate the regions harbouring genes involved in
      neuroblastoma development. A somatic cell fusion experiment was performed between
      the patient's fibroblasts (the only remaining source of patient material) and a
      fast growing Chinese hamster ovary cell line to assure the possibilities to
      perform further research. These somatic cell hybrids indeed contained the human
      translocation chromosomes. Further characterization of the translocation
      breakpoints by FISH (fluorescent in situ hybridisation) resulted in the
      identification of NPPA (formerly PND, the gene for pronatriodilatine) and A12M2
      (an adenovirus integration site) as flanking markers for the 1p breakpoint. The
      17q breakpoint was located between the NF1 (neurofibromatosis 1) gene and the
      SCYA7 (harboring the gene encoding the monocyte chemotactic protein-3). Starting
      from these markers chromosome walking experiments furthered the characterization
      of the chromosomal breakpoint regions and enabled to identify breakpoint
      overlapping cosmids. Sequence analysis of these markers is ongoing and will
      reveal if the breakpoint regions indeed harbour a gene involved in neuroblastoma
      development.

PMID- 12802895
TI  - Vascular targeting: a potential additional anti-cancer treatment.
AB  - Our preclinical in vivo investigations were aimed to evaluate the potential of
      selectively targeting the tumour vasculature as an additional anti-cancer
      strategy. Using a clinical angiography method and the tumour growth delay assay,
      the efficacy of the vascular targeting compound combretastatin A-4 phosphate was
      demonstrated in rat rhabdomyosarcomas: specifically, an inverse efficacy as
      compared to radio- or chemotherapy was measured when comparing small and large
      tumours. The combination of this vascular targeting compound with ionising
      radiation indicated, depending on the timing and the sequence, a potential
      benefit. Within the limits of our experiments, no significant increase in tumour
      growth delay was measured when TNP-470 anti-angiogenesis was given after the
      combretastatin A-4 phosphate treatment. The use of the vascular targeting agent
      did advance the in vivo application of a non-apathogenic anaerobe Clostridium
      transfer system of therapeutic proteins. A strong improvement of the selective
      expression of cytosine deaminase in the tumour microenvironment was observed,
      even with very small tumours. In summary, the present preclinical results
      demonstrate several advantages from the introduction of vascular targeting next
      to classical and novel anti-cancer therapies.

PMID- 12802896
TI  - [Tests for robustness of biomedical and pharmaceutical analytic methods].
AB  - In biomedical and pharmaceutical analysis, especially in the analyses executed in
      the pharmaceutical industry, the quality of the results obtained is strictly
      evaluated and controlled. Therefore, newly developed methods of analysis are
      subjected to a strict and vast method validation. One of the validation criteria
      studied is the determination of the robustness of the method. This is done by
      means of a robustness test. In this manuscript the different steps required to
      set up and interpret a robustness test are discussed and illustrated with a
      number of examples.

PMID- 12802898
TI  - The share of suicide in injury deaths in the South African context:
      sociodemographic distribution.
AB  - This study describes the sociodemographic distribution of suicide deaths compared
      with other injury deaths in South Africa. Cross-sectional data for 26,354 cases
      were extracted from an injury surveillance database. These included all manners
      of injury death from 10 mortuaries for 1999-2000 (approximately 18-20% coverage
      of all injury deaths per year). They were used to examine the distribution of
      suicide across different sex, race and age groupings, and the relative
      involvement of alcohol across manners of death. The share of suicide as a cause
      of death was comparable for males and females, but varied considerably across
      races and age groups. It was twice as high for Whites as for Asians, and four
      times as high as for Coloureds and Blacks. For all races except Whites, suicides
      were concentrated in the younger age groups. Only among Whites was the proportion
      of alcohol-positive suicides higher or comparable with that for other manners of
      death. While homicides and unitentional injury deaths outnumbered suicides
      overall, the relative importance of suicide in some social groups is reason for
      concern. South Africa is a country undergoing profound transformations, and
      differences in the distribution of suicide across sociodemographic groups deserve
      attention.

PMID- 12802899
TI  - Trends in serum cholesterol and lifestyle indicators in Members of the Finnish
      Parliament.
AB  - OBJECTIVE: To examine the extent that public health promotion activity is
      reflected in life styles of national decision makers, by analysing trends in
      coronary heart disease risk factors in Members of the Finnish Parliament (MPs).
      METHODS: The MPs were studied at the beginning of two subsequent 4-year
      parliamentary periods between 1991 and 1999. The studies included analyses of
      serum total cholesterol and high-density lipoprotein (HDL) cholesterol, and a
      questionnaire about alcohol, smoking and physical activity. RESULTS: Serum total
      cholesterol was above the national recommendation of 5.0 mmol/l in 85% of the
      male MPs and 62% of the female MPs. The mean level of serum total cholesterol
      increased in female MPs during the 4-year follow-up period (P < 0.05), and male
      MPs showed an increase in mean HDL cholesterol (P < 0.001). The mean body mass
      index increased in both male (P < 0.01) and female (P < 0.01) MPs during the same
      period. Alcohol consumption, smoking and physical activity were unchanged during
      follow-up. CONCLUSIONS: From the public health perspective, serum cholesterol is
      too high in most MPs, and the level in males is above the national average. Both
      males and females put on weight during the parliamentary period, and male MPs
      also showed an increase in HDL cholesterol, which may be explained by other
      lifestyle factors.

PMID- 12802900
TI  - Transport policy and health inequalities: a health impact assessment of
      Edinburgh's transport policy.
AB  - Health impact assessment (HIA) can be used to examine the relationships between
      inequalities and health. This HIA of Edinburgh's transport policy demonstrates
      how HIA can examine how different transport policies can affect different
      population groupings to varying degrees. In this case, Edinburgh's economy is
      based on tourism, financial services and Government bodies. These need a good
      transport infrastructure, which maintains a vibrant city centre. A transport
      policy that promotes walking, cycling and public transport supports this and is
      also good for health. The HIA suggested that greater spend on public transport
      and supporting sustainable modes of transport was beneficial to health, and
      offered scope to reduce inequalities. This message was understood by the City
      Council and influenced the development of the city's transport and land-use
      strategies. The paper discusses how HIA can influence public policy.

PMID- 12802901
TI  - Factors related to occurrence of hip fracture during a fall on the hip.
AB  - Recently, it has been shown that hip fractures can be effectively prevented by
      use of hip protectors. To determine who would gain most benefit from use of hip
      protectors, we conducted a study with the aim to clarify factors that contribute
      to the occurrence of fracture in individuals who fall on their hip. Hip fracture
      patients were compared with individuals who had fallen on their hip without
      sustaining a fracture. The study group consisted of 123 consecutive hip fracture
      patients aged 70 years or over (mean age 82 years, female 82 years and male 80
      years). The control group comprised 132 individuals (mean age 81 years, female 81
      years and male 80 years) obtained from a prospective study on falls, who had
      experienced a fall that caused a visible soft tissue injury (bruise or wound) at
      the hip or gluteal region without sustaining a fracture. Patients were questioned
      about associated diseases, medications, place of residence, walking ability, need
      for locomotor aids and some activities in daily living (ADL). Patients who
      sustained a hip fracture were more likely to be women, living in long-term
      institutional care, using neuroleptics, dependent in ADL and had more history of
      previous stroke with hemiparesis, more Parkinsonism and lower body mass indexes
      (BMI) than those who did not sustain a fracture on fall on the hip. According to
      a logistical regression model, institutional residence, low BMI and history of
      stroke with hemiplegic status differed between fracture cases and controls.
      Institutional residence, low BMI and history of hemiplegic stroke discriminate
      hip fracture patients from fallers who sustain a soft tissue injury on the hip
      region. In clinical practice, patients who have these characteristics would be
      potential candidates to use hip protectors and other preventive measures.

PMID- 12802902
TI  - The effects of smoking on birthweight-for-gestational-age curves in teenage and
      adult primigravidae.
AB  - OBJECTIVE: To compare the effect of smoking on the birthweight-for-gestational
      age curves of teenage and adult primigravidae. METHODS: A retrospective analysis
      of the perinatal database at the Liverpool Women's Hospital for the years 1997
      1999 for teenage and adult primigravidae. RESULTS: Records on 1157 primigravidae
      were available. There were no significant differences between the mean
      birthweight (3220 g +/- 666 vs 3244 g +/- 680, P = 0.43) and the proportion with
      low birthweight (LBW) babies (8.9% vs 10.6%, P = 0.39) between teenage and adult
      primigravidae, respectively. The percentage of women who smoked increased from
      the middle class (Townsend score -6- - 3) to the working class group (Townsend
      score +4- + 12) for both teenagers (33.3-51.3%) and adults (6.9-29.6%). The mean
      birthweight of babies of smoking mothers was significantly lower than for non
      smoking mothers (3112 g +/- 639 vs 3327 g +/- 663, P = 0.00002). The birthweight
      for-gestational-age pattern was lower at all gestational ages for smoking mothers
      in both the teenage and adult groups. Risk of LBW was significantly increased in
      teenagers who smoked (10.8% vs 3.9%, P < 0.01), but not in adult smokers.
      CONCLUSION: Lower birthweights at all gestational ages were observed in babies of
      teenage and adult mothers who smoked.

PMID- 12802903
TI  - Empirical modelling of population sampling: lessons for designing sentinel
      surveillance.
AB  - BACKGROUND: In order to consider the practical viability of 1% sentinel area
      surveillance for health information in resource-poor settings where complete
      registration is unrealistic, the effects of different sampling procedures on the
      representativeness of 1% population samples have been investigated. METHODS:
      Using the 1991 census of England as a basis for modelling, 20 1% samples, each
      incorporating seven key parameters, were drawn at random from the overall dataset
      by each of eight different sampling procedures. Each sample was compared with the
      'gold standard' of the overall census results, enabling comparisons between the
      different sampling procedures. RESULTS: Representativeness of the 1% samples
      varied considerably between parameters and sampling procedures. At one extreme,
      the proportion of males in the population was distributed such that different
      sampling methods had little effect. On the other hand, samples of a heterogeneous
      parameter such as the proportion of non-whites in the population depended greatly
      on the procedure used. Sampling smaller administrative units tended to be more
      accurate. However, sampling units using probability proportional to size
      generally gave less representative samples. Stratifying urban and rural
      populations in the samples had little effect. Multistage sampling, emulating
      typical demographic surveillance sites, also generally gave less representative
      samples. CONCLUSIONS: It is possible to achieve representative data by taking 1%
      of a national population in a sentinel surveillance approach, but sampling design
      can have an important influence on the outcome. This modelling supports the
      concept of 1% sentinel surveillance for health information in poorer settings,
      where complete data are unavailable.

PMID- 12802905
TI  - Sero-epidemiology of hepatitis B infection in an urban paediatric population in
      Turkey.
AB  - The hepatitis B virus (HBV) seroprevalence rate is known to be 25-60% in Turkey
      with the highest prevalence in the east and south-east. There are insufficient
      data on sero-epidemiology of HBV infection in children living in East Turkey. The
      objective of this study was to estimate the seroprevalence of HBV infection in 6
      17 year olds living in the largest city in East Turkey, and to correlate the
      serological results with epidemiological data. A total of 1091 serum samples were
      tested for hepatititis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs)
      and antibody to hepatitis B core antigen (anti-HBc) using a commercially
      available enzyme-linked immunosorbent assay. The overall seroprevalence rate was
      9.7% and was correlated with age (P = 0.011). No statistical difference was
      detected between subjects with or without risk factors (P = 0.77). The
      seroprevalence of HBsAg was 1.8%, and it was higher in children with a low socio
      economic status (P = 0.047). The educational status of the parents and sibling
      size did not affect the rate of total seroprevalence or HBsAg seroprevalence.
      Although we found that the HBV seroprevalence rate in East Turkey was not as high
      as reported previously, we emphasize the importance of screening children in
      order to identify asymptomatic patients in Turkey until HBV infection is entirely
      eradicated with vaccination programmes.

PMID- 12802904
TI  - Hepatitis C seroprevalence among newly incarcerated inmates in the Texas
      correctional system.
AB  - The seroprevalence of hepatitis C (HCV) infection was examined among a sample of
      incoming inmates in the Texas Department of Criminal Justice (TDCJ) prison
      system. Rates were compared across demographic factors and three types of prison
      facilities: substance abuse felony punishment units (SAFPs), state jails and
      prisons. The study sample consisted of 3712 incoming inmates incarcerated for any
      duration, dating from 1 November 1998 to 31 May 1999. Among males, inmates
      entering SAFPs and state jails had comparable HCV infection rates (29.7 and
      27.0%, respectively) to those entering prisons (27.3%). Among females, inmates
      entering prisons had a higher rate of infection (48.6%) than those entering state
      jails (35.1%) or SAFPs (38.3%). For both genders, blacks exhibited a lower
      overall infection rate than whites and Hispanics, and HCV seroprevalence
      increased in a stepwise fashion with age. All subgroups of TDCJ inmates,
      including those held in alternative correctional facilities, exhibited HCV
      infection rates that were comparable with previous reports of inmate populations,
      but dramatically higher than general community samples. Given that most inmates
      held in alternative facilities will return to the general community in a short
      period of time, understanding the HCV infection rates in these subgroups holds
      particular public health relevance.

PMID- 12802907
TI  - Putting the public back into public health. Part I. A re-definition of public
      health.
AB  - The practice of public health has been criticized as being too involved with a
      narrow, managerial agenda focused on health care rather than the wider horizons
      of public good. Public accountability is central to the practice of public
      health, but is not mentioned in current definitions. We offer a new definition
      that recognizes the centrality of the public, and which should help public health
      professionals interpret their own role: 'Use of theory, experience and evidence
      derived through the population sciences to improve the health of the population,
      in a way that best meets the implicit and explicit needs of the community (the
      public)'.

PMID- 12802906
TI  - Reasons for non-vaccination during national immunization days: a case study in
      Istanbul, Turkey.
AB  - OBJECTIVE: The member states of the 41st World Health Assembly agreed to aim for
      the global eradication of polio by the year 2000. Turkey adopted this goal and
      made substantial progress. In this report, we present the results of a coverage
      and risk factor survey conducted to evaluate vaccine delivery during the 1999
      national immunization days (NIDs) in a large district of Istanbul, Turkey. This
      study provides important information regarding risk factors and reasons for non
      vaccination during the NIDs, defines rumours about the NIDs, and provides
      estimates of vaccination coverage. SETTING AND PARTICIPANTS: A survey was
      conducted 3-10 days after the second round of 1999 NIDs using the standard
      expanded programme on immunization cluster survey method, for each of 10 health
      centre areas in Umraniye. In total, 2102 children were included in the analysis.
      RESULTS: The vaccination coverage rate was 82.2%. Logistic regression analysis
      showed increased risk of non-vaccination in people who did not know the purpose
      of the NIDs, who had not had contact with a mobile vaccination team, who were
      unvaccinated in the first round of 1999 NIDs and who lived in the area of the
      Central Health Centre. Use of primary-level state healthcare facilities for
      routine childhood immunizations, and living in the area of the Adem Yavuz Health
      Centre had significant positive effects on vaccination. CONCLUSIONS: To achieve
      better results, better publicity of national campaigns using mass media, and
      improved use of mobile teams, are necessary.

PMID- 12802908
TI  - Putting the public back into public health. Part II. How can public health be
      accountable to the public?
AB  - The practice of public health involves the application of evidence to improving
      population health, and should be accountable to the public. Accountability to the
      public can be considered either at the individual doctor-patient interface or
      through population-level policy making. The public, at both patient and
      population levels, should join the professionals at each stage of the 'population
      health evidence cycle'-in asking for, collecting, understanding and using
      evidence. A greater appreciation of the non-professional, public perspective
      would represent a substantial commitment to transforming our understanding and
      needs for different kinds of evidence required to improve the health of the
      population.

PMID- 12802909
TI  - Recent advances in the treatment of infant acute myeloid leukemia.
AB  - Infant acute myeloid leukemia (AML) of less than 12 months old is generally
      characterized by a high incidence of acute monoblastic or myelomonoblastic
      leukemia with hyperleukocytosis and extramedullary involvement. Most of the
      leukemic cells have 11q23 translocations, which lead to the MLL gene
      rearrangements. The MLL gene rearrangements occur at a high frequency in
      monoblastic subtype, hyperleukocytosis or young age in infant AML. Compared with
      acute lymphoblastic leukemia, however, it remains unknown whether prenatal origin
      exists in the pathogenesis of infant AML. Recently, the treatment outcome of
      infant AML has been clarified by two study groups, which confirmed the effect of
      intensive chemotherapy including repeated cycles of cytarabine and anthracyclines
      for infant AML. Presence of the MLL gene rearrangements, gender, age and white
      blood cell count showed no influence on the outcome of infant AML. The allogeneic
      hematopoietic stem cell transplantation (HSCT) remains the treatment of choice
      for infant AML when a matched related donor is available. Monitoring of minimal
      residual disease by real-time PCR is a useful technique to predict the outcome or
      efficacy of the treatment in infant AML. Although intensive chemotherapy and/or
      allogeneic HSCT have cured most AML infants, some still relapse and ultimately
      die. A need remains for future development by exploiting the unusual biologic
      properties of leukemic progenitor cells expressing the abnormal MLL gene product.

PMID- 12802910
TI  - Predicting long-term survival in multiple myeloma patients following
      autotransplants.
AB  - Multiple myeloma is a B-cell malignancy with a highly variable outcome. Despite
      the marked recent improvements in its management, especially due to the
      widespread application of high-dose treatment and autologous stem cell
      transplantation, relapses eventually occur in the majority of patients.
      Systematic research at University of Arkansas over the last 10 years, has
      revealed that the absence of unfavorable cytogenetic abnormalities (deletion of
      chromosome 13 and hypodiploidy), low beta-2 microglobulin levels prior to
      transplant, a normal lactate dehydrogenase level at diagnosis and early
      application of high-dose treatment (< 12 months of preceding standard treatment)
      define a subgroup of myeloma patients with a high likelihood of long (> 5 years)
      event-free survival; a sizable minority of these patients may be considered
      cured. Recognition of the importance of these prognostic factors should lead to
      routine cytogenetic evaluation of all patients and early referral to specialized
      transplant centers. Furthermore, patients with less favorable outcome should be
      identified early in their disease course and should be managed with novel and
      hopefully more effective treatments.

PMID- 12802911
TI  - Prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg
      carriers with hemato-oncological neoplasias treated with chemotherapy.
AB  - Reactivation of hepatitis B virus (HBV) infection is well documented complication
      of cytotoxic or immunosuppressive therapy in asymptomatic HBV carriers. Its
      clinical manifestation include fulminant hepatitis which may result in fatal
      liver failure. With the more widespread use of chemotherapy and hematopoietic
      stem cell transplantation, the problem of delivering potentially harmful
      treatment to HBV carriers is becoming increasingly frequent. Until recently the
      management of HBV reactivation has been mainly supportive. With the introduction
      of lamivudine, a highly effective nucleoside analogue against HBV with an
      excellent toxicity profile has become available. However, in light of the
      possibility that its prolonged use may foster the emergence of mutant lamivudine
      resistant HBV strain, caution is required before recommending its widespread use.
      The present review briefly addresses the epidemiological, pathogenetic and
      clinical aspects of HBV reactivation as well the predisposing factors to its
      development. The results obtained with lamivudine both as treatment and as
      prophylaxis of hepatic flares are analysed in detail in order to provide a
      rational basis for clinical decisions before treating HBV carriers with
      chemotherapy.

PMID- 12802912
TI  - Biological significance of the different erythropoietic factors secreted by
      normal human early erythroid cells.
AB  - Evidence is accumulating that autocrine/paracrine regulatory mechanisms play an
      important role in regulating normal hematopoiesis. To support this, various
      growth factors, cytokines and chemokines are expressed and secreted by normal
      early and differentiated hematopoietic cells. In this review, we summarize recent
      advances in the identification and understanding of the role of
      autocrine/paracrine axes in normal human erythropoiesis. We will also address a
      biological significance of the secretion of (i) metalloproteinases which in
      addition to growth factors and cytokines are secreted by normal erythroid cells
      and (ii) membrane-derived microvesicles (MV), that are shed from the surface of
      maturating erythroblasts/reticulocytes, and as we postulate may also play a role
      in intercellular communication. We hypothesize that all these factors together
      play an important role in a crosstalk between erythroid cells and their
      environment. A better understanding of intercellular crosstalk operating in
      normal erythropoiesis and of the mechanisms regulating synthesis of these
      endogenously produced factors may allow us to develop more efficient therapeutic
      strategies to treat various erythropoietic disorders.

PMID- 12802913
TI  - Platelet-activating factor and normal or leukaemic haematopoiesis.
AB  - Platelet-activating factor (PAF), a phospholipid mediator with a wide range of
      actions on mature leukocytes, acts directly during early human haematopoiesis by
      affecting the growth of haematopoietic progenitors and indirectly, by modulating
      cytokine synthesis by bone marrow stromal cells. At this time, its role during
      leukaemic diseases remains speculative. The lack of membrane PAF receptor (PAF-R)
      on leukaemic blasts suggest that this receptor represents a marker of mature
      cells and its membrane induction a consequence of cell maturation. While the
      couple PAF/PAF-R has been largely studied using B cell lines, few results are
      available using B cells of patients with haematopoietic malignancies casting some
      doubts concerning the potential role (if any) of this molecule during leukaemic
      diseases.

PMID- 12802914
TI  - In vitro chemosensitivity testing of selected myeloid cells in acute myeloid
      leukemia.
AB  - In several studies different chemosensitivity assays have been examined in acute
      myeloid leukemia (AML). Some have shown that in vitro chemosensitivity testing is
      an independent prognostic factor but so far no one has been able to show that the
      use of these methods can improve treatment outcome. In an attempt to improve in
      vitro chemosensitivity testing in AML we wanted to establish and evaluate a new
      flow cytometry chemosensitivity assay. After 4 days of incubation viable
      mononuclear myeloid cells were identified by the exclusion of propidium iodide in
      CD13 or CD33 positive cells. Sixty-eight samples from 64 AML patients were
      included. In this study, we showed that the flow cytometry method is feasible in
      AML and we also found some correlations to clinical data. The secondary AML at
      diagnosis showed an in vitro resistance to etoposide and amsacrine that was
      significantly higher compared to de novo AML at diagnosis (p = 0.04 and p =
      0.02). When AML patients at diagnosis were compared to resistant disease/relapse
      patients there was a significantly higher effect of ara-C in the diagnosis group
      (p = 0.03). Responders and non-responders were compared in vitro but we found no
      significant differences. In vitro mitoxantrone was more effective in multidrug
      resistance (MDR) negative cells compared to MDR positive cells (p < 0.01). This
      new method is feasible and makes it possible to selectively evaluate the effect
      of cytotoxic drugs in myeloid cells. Further studies with a larger group of
      patients are needed to evaluate the predictive value of the assay.

PMID- 12802915
TI  - The detection of flow cytometric G-CSF receptor expression and it's effect on
      therapy in acute myeloid leukemia.
AB  - The aim of this study was to evaluate G-CSF receptor (G-CSFr) expression on
      myeloid blasts, its prognostic significance and role in growth factor use and the
      safety and efficacy of G-CSF in the treatment of AML. Expression of G-CSFr,
      CD11a, CD11b, CD11c, CD13, CD33 and CD34 were analyzed with flow cytometry in 101
      patients with AML aged 15-60 years. Results were reported as a percentage of
      positive cells. G-CSFr expression rate was found to be higher in M2 and M3 but
      lower in M5, M6 phenotypes, and in secondary leukemia. Patients were randomized
      for G-CSF use. Of 101 cases 51 received G-CSF. The overall remission rate was
      68.7%. G-CSF use did not seem to have any effect on the remission rates. The
      median time to reach neutrophil counts > or = 1000/microliter in cases receiving
      G-CSF was 23 days, and 28 days in the control group (p < 0.01). G-CSF
      significantly reduced the number of febrile days (p < 0.01). Early and late
      relapses of 8 and 16 were observed during follow-up which was not effected by G
      CSF use. In patients who were G-CSFr(+), G-CSF use did not alter overall survival
      rate. Univariate and multivariate analysis have revealed that not sex, G-CSF use
      or G-CSFr but age, FAB subtype and performance status at diagnosis were the
      important factors on both overall and disease free survival. We have demonstrated
      no beneficial effect of G-CSFr analysis on in vivo G-CSF use.

PMID- 12802916
TI  - Correlation between cell size and CD38 expression in chronic lymphocytic
      leukaemia.
AB  - Both CD38 expression and increased cell size are features of B-lymphocyte
      activation and have been implicated as adverse prognostic factors in B-cell
      chronic lymphocytic leukaemia (CLL). We therefore examined the relationship
      between these two variables by FACS analysis in 140 consecutive CLL patients.
      Using the mean forward-angle light scatter (FSC) as a measure of cell size,
      circulating B lymphocytes were found to be significantly larger in "CD38
      positive" cases (those in which the antigen was expressed in at least 20% of the
      malignant cells) as compared with "CD38-negative" patients (p = 0.029).
      Furthermore, within individual cases B lymphocytes expressing CD38 were, on
      average, significantly larger than cells that did not express the antigen (p <
      0.0001). Finally, when B lymphocytes of individual "CD38-positive" cases were
      arbitrarily divided into large and small subpopulations using their mean FSC as a
      cut-off, CD38 was found to be more frequently expressed on the larger cells (p <
      0.0001). This strong positive correlation between CD38 expression and cell size
      implicates cell activation as a possible underlying determinant of both tumour
      cell phenotype and clinical outcome in CLL.

PMID- 12802917
TI  - ACOD, a modified CHOP regimen for elderly patients with aggressive non-Hodgkin's
      lymphoma.
AB  - The aim of this study is to verify the feasibility and the clinical activity of a
      new CHOP-like schedule (ACOD) with a fractionated days 1 and 8 administration in
      elderly patients. This regimen was chosen in the attempt to allow a sufficient
      dose intensity (DI) of each drug with better compliance. Fifty-two patients, (74
      years, median age), with diffuse large B cell non-Hodgkin's lymphoma were
      retrospectively evaluated. Patients received ADM 25 mg/sqm, CTX 500 mg/sqm, VCR
      1.2 mg/sqm (max 2 mg intravenously) days 1 and 8 and PDN 50 mg orally, days 1-8.
      Results showed that 54% of patients reached a complete remission, 21% a partial
      remission with an overall response rate of 75%. Two-thirds of the patients
      received at least 70% of the planned dose of cyclophosphamide and doxorubicin and
      50% of vincristine and prednisone. The median duration of follow up was 12.6
      months (range 0.7-61.4). The estimated median OS was 15.2 months (95%CI = [11.6,
      not estimable]); the estimated median PFS was 5.7 months (95%CI = [5.12, not
      estimable]). After 2 years, the proportion of patients alive was 47% (95%CI = 34
      64%) and the proportion of patients free from progression was 39% (95%CI = 27
      57%). Grade 3-4 leukopenia was observed in 61% of patients with 11% of febrile
      neutropenia. In conclusion, the ACOD chemotherapy regimen seems safe and feasible
      in elderly patients. This schedule allowed a sufficient DI of chemotherapic
      agents with clinical results very similar to those recorded with the standard
      CHOP regimen in young adults.

PMID- 12802918
TI  - Characterization of T-cell non-Hodgkin's lymphoma and its association with
      Epstein-Barr virus in Pakistani patients.
AB  - This study analyzes the prevalence of T-cell non-Hodgkin's lymphoma (T-NHL) in a
      major referral center of Pakistan and its association with Epstein-Barr virus
      (EBV). Ninety-two cases of T-NHL were characterized on the basis of morphology,
      immunohistochemistry and genetic features. The prevalence of T-NHL was 22.2% of
      the total NHLs diagnosed during the eight years period (1992-1999). Polymerase
      chain reaction (PCR) technique was used to assess T-cell clonality in paraffin
      embedded tissues of known T-NHL. Amplifiable DNA was isolated from all the cases,
      which were further studied for T-cell receptor (TcR)-beta, gamma, delta, and IgH
      chain gene rearrangements. Out of 92 cases 51 cases showed clonal product and 33
      demonstrated polyclonal smear for beta, gamma, or delta chain genes,
      respectively, whereas 8 cases exhibited IgH chain gene rearrangement for FR2
      region. This study demonstrated frequent presence of EBV in T-NHL (55.4%) by PCR,
      which were further tested for the localization of the virus by in situ
      hybridization (ISH). The extent of polymorphism in EBV genome was studied by
      single stranded conformation polymorphism (SSCP) technique for Bam HI E, K, N and
      Z regions. Hypervariability in Bam HI K, and N regions was noticeably higher
      compared to E or Z regions. In conclusion, our study demonstrated that the
      prevalence of T-NHL in Pakistan is slightly higher to that reported for Western
      communities. In addition, the frequency of EBV genome in T-NHL is intermediate as
      compared to other studies. No association was established between EBV variants
      differentiated on the basis of sequence heterogeneity in Bam HI K, N, E and Z
      regions with the manifestation of different subsets of T-NHL.

PMID- 12802919
TI  - Poor mobilization of peripheral blood stem cells is a risk factor for worse
      outcome in lymphoma patients undergoing autologous stem cell transplantation.
AB  - The effect of poor blood stem cells mobilization on the outcome of autologous
      stem cell transplantation (ASCT) has not been well studied. Our aim is to
      evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing
      ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's
      lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability
      to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume
      aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and
      group 2 = good mobilizers. The poor mobilizers received lower median transplant
      CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001),
      were more heavily pretreated (P = 0.01), and required higher number of aphereses
      for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in
      groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival
      (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis
      showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6),
      elevated LDH before transplant, and poor mobilization were significant prognostic
      factors for poor PFS, while only the first three were significant for worse OS.
      Multivariate analysis using these same four factors revealed that number of pre
      transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P =
      0.0007) were the only independent predictive factors for worse overall outcome.
      In conclusion, our data show that poor mobilization could indicate poor outcome
      in lymphoma patients undergoing ASCT, however, it is more likely to be a
      reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re
      infused in this group of patients.

PMID- 12802920
TI  - Extranodal marginal zone B-cell lymphoma of MALT-type of the lung: single-center
      experience with 12 patients.
AB  - The lung is a relatively rare site for mucosa-associated lymphoid tissue (MALT)
      lymphomas: we report the largest available single-center series of patients with
      this presentation. From August 1992 to October 2000, 12 patients with untreated
      primary low-grade MALT lymphoma of the lung were submitted either to chemotherapy
      alone (n = 8), surgery alone (n = 2) or surgery plus chemotherapy (n = 2). At
      diagnosis, 6 (50%) were asymptomatic and 6 (50%) had nonspecific pulmonary
      symptoms. The most common radiologic findings were a pulmonary infiltrate (7
      cases) and a mass lesion (5 cases). Histological diagnosis was obtained with
      transbronchial lung biopsy/bronchoalveolar lavage (BAL) (6 cases), with
      transthoracic needle biopsy (1 case), or an open thoracotomy (5 cases). All
      patients had stage IE. All 12 (100%) achieved complete remission; 3 (25%) local
      recurrences were observed. The global 6-year survival rate was 100% with a
      relapse-free survival rate of 50%. In conclusion, these data underline the
      diagnostic utility of BAL and the therapeutic efficacy of a chemotherapeutic
      strategy based on regimens such as N-CVP in the context of localized MALT
      lymphoma of the lung.

PMID- 12802921
TI  - Primary ovarian lymphoma: report of cases and review of literature.
AB  - Primary female reproductive system lymphomas are distinctly uncommon. We report
      two cases with primary ovarian non Hodgkin's lymphoma (NHL) having unilateral
      involvement in one case while the other had bilateral ovarian involvement. Both
      cases initially presented with ovarian enlargement. The median size of the tumour
      was 5.8 x 5 cm2. Histologically, by using the WHO classification, one lesion was
      classified as diffuse small B cell phenotype of intermediate grade and the other
      as diffuse high grade, B cell phenotype. On the basis of staging studies and
      clinical follow up, we conclude that both of the neoplasms in the report arose in
      the ovary. Both of the patients are disease free at 24 months and 6 months of
      follow up respectively, following excision and chemotherapy. We conclude that
      that the complete remission and failure free survival of patients with ovarian
      NHL treated with appropriate treatment appear to be similar to that of patients
      with extranodal NHL.

PMID- 12802922
TI  - Treatment of relapsing refractory diffuse large cell lymphoma after matched
      unrelated donor bone marrow transplant with immunosuppression withdrawal and
      rituximab.
AB  - A 31-year-old man with a diffuse large-cell lymphoma in first refractory relapse
      received a bone marrow transplant (BMT) from a matched unrelated donor using
      CAMPATH-1H, carmustine, etoposide, cytarabine and melphalan as conditioning
      regimen, and methotrexate and tacrolimus for graft-versus-host disease (GVHD)
      prophylaxis. The transplant was complicated by grade II skin acute GVHD. Lymphoma
      relapse occurred 4 months post-transplant. Immunosuppression withdrawal plus
      rituximab induced a complete response. He remains in complete remission (CR) 11
      months post-immunosuppression withdrawal and 15 months post-transplant.

PMID- 12802924
TI  - Customized mitogen or antibody treatments enhance the sensitivity of lymphoid
      tumors to 5-fluorouracil in vitro and in vivo.
AB  - Despite impressive cure rates for certain leukemias and lymphomas, lymphoid
      tumors are responsible for thousands of deaths per year. Refractory disease
      remains difficult to control, encouraging the development of new treatment
      options. 5-fluorouracil (5-FU) has been successfully used to control (or cure) a
      variety of tumors, but has been only rarely applied to tumors of the lymphoid
      lineage. Here we demonstrate that the effects of 5-FU on lymphoid tumors can be
      enhanced by the concomitant binding of cellular membrane molecules with mitogen
      or antibody. When used in combination with 5-FU, mitogen treatments: (i) enhance
      the association of drug with cells, (ii) reduce cell proliferation in vitro and
      (iii) inhibit cell growth in a mouse B-cell tumor model.

PMID- 12802923
TI  - Alterations of mRNA splicing in primary effusion lymphomas.
AB  - Primary effusion lymphoma (PEL) is a unique form of malignant lymphoma associated
      with infection by the Kaposi's sarcoma-associated herpesvirus (KSHV)/human
      herpesvirus-8 (HHV-8). The majority of PELs also contain the EBV genome. Although
      viral infection is believed to play a critical role in the pathogenesis of PEL,
      it has been suggested that additional molecular lesions are required for the
      development of PEL. Alternative splicing of pre-mRNA is an important mechanism in
      the regulation of cellular and viral gene expression. Deregulation of pre-mRNA
      splicing may shift the gene expression balance and lead to the development of
      cancer. In order to investigate mRNA splicing in PELs, we examined mRNA splicing
      of three genes, DNA polymerase beta (pol beta), Bcl-x and CD45, in eight PEL cell
      lines. We found that the average variant percentage of pol beta in PEL cell lines
      is two times higher than in peripheral blood mononuclear cells (PBMC) and that
      the variant pattern of genes bcl-x and CD45 is quite different in PEL cell lines
      than in PBMC. In addition, we also found that the percentage of variant pol beta
      increased two-fold in PBMC following Epstein-Barr virus (EBV) infection.
      Therefore, viral infection may contribute to mRNA alternative splicing in PEL. In
      order to explore the mechanism by which viral infection affects mRNA splicing, we
      also examined the roles of genes KS-SM, SM and EBERs and viral copies in mRNA
      splicing. Our findings indicate that various factors acting as positive or
      negative regulators may be involved in mRNA alternative splicing caused by viral
      infection. In conclusion, mRNA splicing in PEL can be altered by viral infection
      and this alteration may contribute to the pathogenesis of PEL.

PMID- 12802925
TI  - A novel c-kit positive biphenotypic acute leukemia cell line, TMBL-1, carrying a
      p53 point mutation.
AB  - We established and characterized a c-kit positive cell line from the bone marrow
      of a patient with biphenotypic acute leukemia (BAL). The cell line, designated
      TMBL-1, carried a His-175 mutant p53. The immunophenotype of the primary leukemia
      cells at diagnosis was cytoplasmic CD3+, CD7+, CD13+, CD33-, interleukin-7 (IL-7)
      receptor+ and c-kit -. However, leukemia cells in relapse and TMBL-1 cells were
      CD33+ and c-kit +. Immunophenotypically, TMBL-1 is a BAL cell line that
      coexpresses T-lymphoid and myeloid markers which fulfill the criteria of the
      European Group for the Immunological Characterization of Leukemia. Stem cell
      factor (SCF), a key regulator of hematopoiesis signaling through c-kit, enhanced
      the proliferation of TMBL-1 cells. Direct sequencing revealed the conversion at
      codon 175 of the p53 gene in the TMBL-1 cells. Primary leukemia cells in relapse
      also carried the same point mutation but not at diagnosis. Moreover, TMBL-1 cells
      are sensitive to paclitaxel, which could induce p53-independent apoptosis. The
      biphenotypic features and p53 mutation may be associated with progression to a
      more malignant type. This cell line may provide new information on the role of
      SCF in the overlapping area between early T-lymphoid/myeloid cells, and help in
      the design of new therapies targeted towards p53 mutations.

PMID- 12802926
TI  - Hodgkin's type of Richter's syndrome in familial chronic lymphocytic leukemia
      treated with cladribine and cyclophosphamide.
AB  - Second malignancies are frequent complications in patients with chronic
      lymphocytic leukemia (CLL). Hodgkin's disease (HD) has been observed in
      approximately 0.5% of the patients with CLL and is known as Hodgkin's type
      Richter's syndrome (H-RS). We present a 64-year-old male patient with a familial
      history of CLL who developed H-RS in abdominal lymph nodes 6 years after CLL
      diagnosis and 18 months after treatment with cladribine (2-CdA) and
      cyclophosphamide. HD was diagnosed by fine needle aspiration. The disease was
      refractory to treatment with two courses of CHOP and three courses of ABVD
      chemotherapy. In the current literature we found case reports of only 6 patients
      with H-RS who were treated with fludarabine (FA) before transformation, and, to
      our knowledge the presented patient is the first to develop H-RS after treatment
      with 2-CdA combined with cyclophosphamide. He is also the first published patient
      with familial CLL in whom this complication developed.

PMID- 12802927
TI  - Chronic myeloid leukemia associated with B-cell chronic lymphocytic leukemia:
      evidence of two separate clones as shown by combined cell-sorting and
      fluorescence in situ hybridisation.
AB  - The simultaneous occurrence of Philadelphia positive chronic myeloid leukemia
      (Ph+ CML) and B-cell chronic lymphocytic leukemia (B-CLL) is a rare event which
      raises the possibility that the two malignant clones derive from a common, or
      distinct, malignant stem cells. In this study, we used combined CD19-based cell
      sorting and fluorescence in situ hybridisation (FISH) to investigate whether or
      not the BCR-ABL fusion gene was present in the malignant B-cells of a patient who
      presented a Ph+ CML/B-CLL association. The CD19+ cells lacked the BCR-ABL
      rearrangement whereas all CD19-cells exhibited the fusion gene. This result
      demonstrates that B-cell transformation occurred in a Ph-B-cell subset.

PMID- 12802928
TI  - Pulmonary alveolar proteinosis in a patient with acute lymphoid leukemia
      regression after G-CSF therapy.
AB  - Pulmonary alveolar proteinosis (PAP) is the intra-alveolar accumulation of
      periodic-acid schiff (PAS) positive material. PAP is one of the underrecognized
      causes of pulmonary infiltrates in patients with hematologic malignancies. Here,
      we present a patient with acute lymphoid leukemia (ALL) in first remission that
      developed fever and diffuse pulmonary infiltrates during the neutropenic stage of
      consolidation chemotherapy. The histopathologic examination of bronchoalveolar
      lavage (BAL) fluid and transbronchial biopsy specimen demonstrated the presence
      of PAS-positive eosinophilic material. Empirical antibiotherapy and granulocyte
      colony stimulating factor (G-CSF) were given. After the correction of neutropenia
      with G-CSF, the patient's fever disappeared, acute phase reactants decreased,
      pulmonary infiltrates resolved. We present this case because it was the first
      patient in whom the correction of neutropenia with G-CSF was followed by
      resolution of PAP.

PMID- 12802929
TI  - MALT lymphoma at the base of the tongue developing without any background of
      immunodeficiency or autoimmune disease.
AB  - We report a very rare case of a mucosa-associated lymphoid tissue (MALT) lymphoma
      of the base of the tongue. A 61-year-old woman was admitted to our hospital for
      further examination of a 12 mm x 15 mm x 5 mm tongue tumor. Histological
      examination of the tumor revealed a marked lymphoepithelial lesion. Lymphoma
      cells expressed CD5(-), CD10(-), CD19(+), CD20(+) on the surface of the cells by
      fluorescence activated cell sorter, and the genotypic analysis of the tumor cells
      revealed the presence of immunoglobulin heavy chain rearrangement and the absence
      of BCL-2 gene rearrangement by southern blot hybridization. Furthermore, neither
      the t(11;18) (q21;q21) translocation nor trisomy 3 was detected in lymphoma cells
      by fluorescence in situ hybridization method. The tongue tumor was completely
      resected and no recurrence has been noted in the 13 months to date.

PMID- 12802931
TI  - Multiple complete remissions in a patient with acute myeloid leukemia (M4eo) with
      low-dose cytosine arabinoside and all-trans retinoic acid.
AB  - A 54-year-old female with acute myeloid leukemia (AML) (FAB M4eo) was treated at
      second relapse with a combination of low-dose cytosine arabinoside (LDAraC) (20
      mg b.i.d. subcutaneously) and all-trans retinoic acid (ATRA) (45 mg/m2/d orally)
      on days 1-10. The patient achieved a complete hematological remission after the
      first cycle and was consolidated with three similar cycles at four-week
      intervals. Subsequently, the patient relapsed several times. Altogether seven
      complete hematological remissions including some cytogenetic remissions were
      induced with the same regimen. The patient survived 81 months after the start
      with LDAraC-ATRA regimen. This low-toxicity regimen may be useful in some
      patients with poor-risk AML.

PMID- 12802930
TI  - Successful treatment with Erwinia L-asparaginase for recurrent natural killer/T
      cell lymphoma.
AB  - We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after
      autologous peripheral blood stem cell transplantation (auto-PBSCT) and was
      successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase.
      A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed
      as having nasal type NK/T cell lymphoma on the basis of histopathological and
      flowcytometric findings of tumor, revealing diffuse infiltration of atypical
      lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but
      not CD3. He had tumor infiltration in the bone marrow and at the right lower lung
      field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and
      prednisolone) therapy, the patient achieved complete remission and received high
      dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg
      10 months later. Despite salvage chemotherapy, followed by local irradiation and
      surgical amputation, a tumor recurred at the left upper gingiva 10 days after.
      Using E. coli L-asparaginase (6000 U/m2/day), the tumor regressed, fever was
      alleviated and the serum lactate dehydrogenase decreased to normal range after
      several days. The asparagine synthetase expression in tumor cells was
      immunohistochemically negative on paraffin-embedded tissues. Because of the
      anaphylactoid reaction developing after E. coli L-asparaginase, alternative
      Erwinia L-asparaginase (6000 U/m2/day) was administered, resulting in regression
      of tumor and fever lysis. L-asparaginase is a promising agent for the treatment
      of NK/T cell lymphoma.

PMID- 12802932
TI  - Intravascular lymphoma presenting with cauda equina syndrome: treated with CHOP
      and rituxan.

PMID- 12802933
TI  - Severe autoimmune hemolytic anemia following rituximab therapy in a patient with
      a lymphoproliferative disorder.
AB  - Rituximab (chimeric anti-CD20 IgG1 monoclonal antibody) is effective in the
      treatment of relapsed/refractory low-grade lymphomas of B-cell origin as well as
      in diffuse large B-cell lymphoma. Several reports also demonstrated the efficacy
      of rituximab for the treatment of autoimmune cytopenia, especially for cold
      agglutinin disease. We report the first case, to our knowledge, of rituximab
      related autoimmune hemolytic anemia. The pathophysiological mechanisms remain
      unknown, although the drug could act through massive cytokines liberation after
      destruction of CD20 positive cells by rituximab.

PMID- 12802934
TI  - Successful treatment with intermediate dose cytosine arabinoside for
      myelodysplastic syndrome with acute myelofibrosis.

PMID- 12802935
TI  - Multiple myeloma associated with systemic lupus erythematosus.
AB  - A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is
      presented; the lupus diagnosis was put together with the diagnosis of myeloma but
      the symptoms had commenced a few years before. The putative mechanisms underlying
      this unusual combination are discussed.

PMID- 12802936
TI  - Early second leukaemia in a patient with successfully treated acute promyelocytic
      leukaemia.

PMID- 12802937
TI  - Imaging and anatomy of the normal intracranial venous system.
AB  - The intracranial venous system is a complex three-dimensional structure that is
      often asymmetric and considerably more variable than the arterial anatomy. The
      traditional approach has been to evaluate venous phase of catheter angiography.
      However, non-invasive imaging is now playing a greater role in evaluating the
      intracranial venous system in both healthy and diseased states. MR angiography,
      and especially Gd-enhanced 3D MRA, has recently emerged and offers excellent
      visualization of venous morphology from multiple orientations. An overview of the
      current non-invasive MRA methods and their applications has been provided during
      depiction of normal venous anatomy.

PMID- 12802938
TI  - Venous variations of the brain and cranial vault.
AB  - Vascular anomalies involving both intra- and extra-cranial structures are more
      common than previously thought. It is important to evaluate the brain and its
      coverings carefully when imaging cervicofacial vascular malformations. Scientific
      knowledge regarding developmental mechanisms responsible for blood vessel
      formation is increasing rapidly and, hopefully, will contribute to better
      understanding of these clinical and imaging "patterns."

PMID- 12802939
TI  - Intracranial cavernous malformations.
AB  - Cavernous malformations are commonly being recognized on CT and MR imaging in
      both asymptomatic and symptomatic patients. The diagnosis of CMs can often be
      made on MR imaging based on the characteristic morphology of the subacute and
      chronic blood products. An atypical appearance of a CM in the setting of a recent
      hemorrhage requires follow-up imaging to confirm the diagnosis. Deep CMs have a
      significant clinical event rate that justifies close follow up or surgical
      treatment if possible.

PMID- 12802940
TI  - Hydrovenous disorders in pediatric intracranial arteriovenous fistula.
AB  - High-flow AVFs are a challenging problem in the pediatric age group. Venous
      occlusive changes develop as part of the dynamic response to these fistulas. The
      development of adequate venous collateral flow circumvents the destructive
      sequelae of longstanding venous hypertension. Without adequate collaterals,
      venous hypertension develops. Venous hypertension interferes with CSF resorption,
      resulting in increased brain water. Ventriculomegaly and tonsillar prolapse
      commonly develop and are reversible if therapeutic intervention is done in a
      timely fashion. If left untreated, chronic venous ischemic changes develop, which
      result in delay in important developmental milestones.

PMID- 12802941
TI  - Venous congestive encephalopathy related to cranial dural arteriovenous fistulas.
AB  - Cranial DAVFs present with a wide spectrum of clinical findings from pulsatile
      tinnitus alone to intracranial hemorrhage and NHND. The neurologic sequelae are a
      consequence of venous hypertension and venous congestion. DAVFs with CVR can
      present with or develop a VCE that can be recognized on MR imaging as a diffuse
      T2 hyperintensity in the deep white matter of the cerebral or cerebellar
      hemispheres. The T2 hyperintensity has a characteristic peripheral enhancement.
      The telltale sign on MR imaging is the plethora of prominent pial vessels on the
      surface of the brain that are the engorged cortical veins participating in the
      cortical venous reflux. Selective angiography is critical for the accurate
      assessment of the CVR. DAVFs with CVR require prompt treatment, either
      endovascular alone or a combination of endovascular treatment and surgery.

PMID- 12802942
TI  - Venous manifestations of spinal arteriovenous fistulas.
AB  - Spinal dural AVFs, the most common type of spinal arteriovenous malformations,
      are symptomatic because of venous hypertension and congestion. This has been
      referred to as venous congestive myelopathy. The typical MRI findings that
      reflect venous congestive myelopathy include peripheral T2 hypointensity that
      outlines a T2 hyperintensity within a swollen spinal cord. Enlarged perimedullary
      vessels are typically present. Contrast-enhanced MRA has become instrumental in
      localizing the site of these fistulas. Spinal epidural AVFs and the perimedullary
      spinal cord AVFs may also present with a congestive myelopathy and have similar
      findings on MRI. Angiography remains the gold standard for characterization of
      the angioarchitecture of spinal vascular malformations. [figure: see text]
      Multidisciplinary treatment planning is mandatory and requires knowledge of the
      natural history of these vascular lesions.

PMID- 12802943
TI  - Radiologic findings and clinical significance of venous compartment of brain
      arteriovenous shunts.
AB  - The venous compartment of brain AVS is closely related to the development of
      various clinical consequences, including hemorrhage, seizure, and neurologic
      deficit. Therefore, understanding the venous etiology of the clinical symptoms
      and the imaging characteristics of partial or complete venous outlet thrombosis
      is critical for the proper management of patients with brain AVSs.

PMID- 12802944
TI  - Sinovenous thrombosis in children.
AB  - Sinus thrombosis in children is increasingly recognized; however, the diagnosis
      is still frequently missed. Children may have an increased incidence of this
      disorder compared with adults, and neonates are at greatly increased risk
      compared with older children. Childhood CSVT carries significant long-term
      sequelae that include death or neurologic deficits in nearly 50% of cases.
      Neonates are not spared from these sequelae. At present, the approach to
      treatment is empiric but in the past decade treatment with anti-coagulants is
      supported by the unacceptable rates of adverse outcomes, the pathophysiology of
      CSVT, and the data supporting the efficacy and safety of anti-coagulation for
      adult CSVT. Among the most significant current and future developments in
      childhood CSVT is the evolution of accurate, noninvasive and economical
      neuroimaging techniques. The latter techniques have the potential to increase the
      detection rate of childhood CSVT, improve our understanding of the
      pathophysiology and define important subgroups of patients who best respond to
      treatment. An international interest in childhood CSVT is developing and, in the
      next decade, will enable the necessary multi-national clinical trials to provide
      evidence-based treatments and decrease the adverse outcomes.

PMID- 12802945
TI  - Cerebral venous thrombosis in adults: the role of imaging evaluation and
      management.
AB  - Clinical suspicion and excellent neuroimaging are crucial in making a diagnosis
      of CVT. Intravascular or dural sinus thrombus can be visualized on CT and MRI.
      Brain edema and intracranial hemorrhage that do not conform to an arterial
      territory are frequently evident on CT and MRI. Heparin treatment is accepted as
      the first-line treatment of CVT. Endovascular treatment for management of CVT is
      usually reserved for selected cases after failure of anticoagulation.

PMID- 12802946
TI  - Teaching an old dog new tricks.

PMID- 12802947
TI  - Maximizing a transport platform through computer technology.
AB  - One of the most recent innovations coalescing computer technology and medical
      care is the further development of integrated medical component technology
      coupled with a computer subsystem. One such example is the self-contained patient
      transport system known as the Life Support for Trauma and Transport (LSTAT(tm)).
      The LSTAT creates a new transport platform that integrates the most current
      medical monitoring and therapeutic capabilities with computer processing
      capacity, creating the first "smart litter". The LSTAT is built around a computer
      system that is network capable and acts as the data hub for multiple medical
      devices and utilities, including data, power, and oxygen systems. The system logs
      patient and device data in a simultaneous, time-synchronized, continuous format,
      allowing electronic transmission, storage, and electronic documentation. The
      third-generation LSTAT includes an oxygen system, ventilator, clinical point-of
      care blood analyzer, suction, defibrillator, infusion pump, and physiologic
      monitor, as well as on-board power and oxygen systems. The developers of LSTAT
      and other developers have the ability to further expand integrative component
      technology by developing and integrating clinical decision support systems.

PMID- 12802948
TI  - Using Lewin's force field analysis in implementing a nursing information system.
AB  - Change is a regular occurrence in the healthcare environment. The computerization
      of nursing systems is one aspect of the changes taking place in the information
      revolution. As a result, nurses have widely varying attitudes toward computers
      and change in the workplace. To transition the nursing team effectively from one
      system to another, the nurse informaticist must be aware of the factors that
      encourage and those that impede the change. Strategies must be developed to
      assist nurses in moving forward with the transition. This article presents a
      theoretical discussion of how Lewin's Force Field Analysis Model could be applied
      in the practice setting to implement a nursing information system successfully.

PMID- 12802949
TI  - Computers in patient education.
AB  - Nurses in practice have an increasing need to become aware of the computer-based
      resources available and the evidence regarding their use in the process of
      patient education. This synthesis of the literature examines research related to
      computer-based patient education. A particular focus is placed on the nurse
      clinician's perspective and the role of the nurse as a patient educator in the
      digital age. Two primary healthcare database resources, MEDLINE and CINAHL, were
      selected for review of the current literature. A listing of articles related to
      the use of computer technology in patient education was obtained from both of
      these databases. The search strategy included exploding the subject heading terms
      "computer" and "patient education," and included articles from 1971 to 2001.
      Computer-based patient education is an effective strategy for improving
      healthcare knowledge and clinical outcomes. Computer-based learning can be
      tailored to the individual's age and specific learning needs. Furthermore,
      although access to computer-based resources continues to be a barrier for some,
      socioeconomic disparities have no reported impact on patients' abilities to use
      computer-based technologies effectively.

PMID- 12802950
TI  - Criteria used by nurses to evaluate practice-related information on the World
      Wide Web.
AB  - Existing criteria used to evaluate information on the World Wide Web often are
      not related to nursing, especially in relation to clinical and evidence-based
      practice. Published criteria have been found orientated to the health-consumer,
      medicine, or general information. In this study, the process by which nurses
      evaluate practice-related information and the associated evaluative nursing
      criteria were investigated using a grounded theory approach. In the first stage
      of this ongoing investigation, semistructured interviews were used to collect
      data from UK postregistration nursing students. The findings from this initial
      study provided indications of the process and the criteria for evaluating
      information on the World Wide Web. Participating students identified intuition as
      part of the evaluative process. They identified some criteria similar to existing
      standards, but critically, with additional criteria that are nursing practice
      related. Because these new criteria are significant for evaluating nursing
      information, further refinement of these findings is being undertaken through the
      next stage of the research program.

PMID- 12802951
TI  - Home care nurses' attitudes toward computers. A confirmatory factor analysis of
      the Stronge and Brodt instrument.
AB  - Point-of-care technology for home care use will be the final step in enterprise
      wide healthcare electronic communications. Successful implementation of home care
      point-of-care technology hinges upon nurses' attitudes toward point-of-care
      technology and its use in clinical practice. This study addresses the factors
      associated with home care nurses' attitudes using Stronge and Brodt's Nurse
      Attitudes Toward Computers instrument. In this study, the Nurses Attitudes Toward
      Computers instrument was administered to a convenience sample of 138 nurses
      employed by a large midwestern home care agency, with an 88% response rate.
      Confirmatory factor analysis corroborated the Nurses Attitudes Toward Computers'
      3-dimensional factor structure for practicing nurses, which was labeled as
      nurses' work, security issues, and perceived barriers. Results from the
      confirmatory factor analysis also suggest that these 3 factors are internally
      correlated and represent multiple dimensions of a higher order construct labeled
      as nurses' attitudes toward computers. Additionally, two of these factors,
      nurses' work and perceived barriers, each appears to explain more variance in
      nurses' attitudes toward computers than security issues. Instrument reliability
      was high for the sample (.90), with subscale reliabilities ranging from 86 to 70.

PMID- 12802952
TI  - Epidemiology of toxoplasmosis.

PMID- 12802953
TI  - [Ophthalmologic aftercare of congenital toxoplasmosis].

PMID- 12802954
TI  - Congenital toxoplasmosis: therapeutic strategies.

PMID- 12802955
TI  - [Congenital toxoplasmosis: different preventative strategies].

PMID- 12802956
TI  - Official recommendations and strategy for prevention of congenital toxoplasmosis
      in Germany.

PMID- 12802957
TI  - Prevention of congenital toxoplasmosis in Austria.

PMID- 12802958
TI  - Screening for toxoplasmosis during pregnancy: the situation in Belgium.

PMID- 12802959
TI  - Current situation regarding toxoplasmosis in Finland.

PMID- 12802960
TI  - [Prevention of congenital toxoplasmosis: official recommendations and management
      in France].

PMID- 12802961
TI  - Failure to implement a preventive strategy against congenital toxoplasmosis in
      Italy.

PMID- 12802962
TI  - Prevention of congenital toxoplasmosis in Norway.

PMID- 12802963
TI  - [Legal dispositions and preventive strategies in congenital toxoplasmosis in
      Portugal].

PMID- 12802964
TI  - Congenital toxoplasma infection in the UK.

PMID- 12802965
TI  - [Multidisciplinary approach to congenital toxoplasmosis. Differences in European
      strategies].

PMID- 12802967
TI  - [Prenatal biological diagnosis of congenital toxoplasmosis: value and limits].

PMID- 12802966
TI  - [Diagnosis and methods. The mother: evaluation of risks and data collection.
      Serology].

PMID- 12802968
TI  - [Ultrasonographic signs of congenital toxoplasmosis].

PMID- 12802969
TI  - [Congenital toxoplasmosis: neonatal biological diagnosis and surveillance].

PMID- 12802970
TI  - [Clinical management of congenital toxoplasmosis].

PMID- 12802971
TI  - [Toxoplasmosis polymorphism and its clinical consequences].

PMID- 12802972
TI  - Public health heros.

PMID- 12802973
TI  - New skills for a new age: leading the introduction of public health concepts in
      healthcare curricula.
AB  - Health policy in the UK is going through significant changes. At the heart of the
      transformation is a dedicated focus on public health. The new primary-care-based
      health system will not only be premised on a specialist public health workforce,
      but also on broader based public-health-oriented health professionals. Within
      primary care, widening the foundation of health professionals with public health
      competencies suggests that higher education bodies will need to adapt their
      curricula to an approach that highlights population-based health principles,
      preventive philosophy, and public health concepts and methods. The first part of
      this paper describes the mapping of the public health content of healthcare
      curricula at one university in England, based on the 10 public health standard
      areas of competencies of the Faculty of Public Health Medicine. The second part
      examines, through the findings of a strengths, weaknesses, opportunities, threats
      (SWOT) analysis, the factors that advocates for a public-health-oriented
      educational strategy must examine before embarking on the instigation and
      development of public health concepts in the healthcare curricula. The aspects
      that necessitate consideration include strengths such as the prevailing policy,
      market forces, commitment, and motivation to the effort, and the availability of
      resources, information and external contacts. Features such as political drive
      and advocacy, interest in the education debate, collaborative links through joint
      working and partnerships, and ongoing internal reforms and restructuring could
      all act as opportunities. However, resistance and anxiety are to be expected, the
      operationalization of the effort and empowerment of those leading it need to be
      thought about, and issues of control and interests are critical. The presence of
      conflicting priorities and competition or the lack of vision and directives, or
      uncertainty about change, could act as threats and barriers to the effort. If
      shifting the 'traditional' healthcare curricula to a more 'innovative' public
      health-oriented one is to be a success, administrators of educational change will
      need to take into account a 'melange' of factors and stakeholders involved in a
      gradual and incremental process.

PMID- 12802974
TI  - The use of pharmacy immunization services in rural communities.
AB  - Pharmacies have been recommended as alternative sites for the delivery of
      immunization services, especially to medically underserved adults and children in
      inner cities and rural areas. Currently, 35 of 50 states in the USA have
      legalized the administration of vaccines by pharmacists on the basis of certain
      training requirements and specific protocols. Since the role of pharmacists is
      expected to expand, it is important to assess the factors that would enable them
      to improve the delivery of immunization services and the acceptance of these
      services by communities. It is particularly important for pharmacists to have
      knowledge of community circumstances and be able to respond to community needs.
      This case study of a pharmacy immunization programme (PIP) in rural West Virginia
      assessed how well pharmacists were aware of community circumstances and which
      community factors affected the utilization of pharmacy-delivered immunizations.
      Our findings suggest that although pharmacists played important roles as
      facilitators, hosts and motivators in PIP, they overestimated the trust placed in
      them by community members. The convenient locations of pharmacies and the
      convenient times when they offered immunization services were found to be the
      determining factors of mothers' decisions to take their children to these places
      for their vaccinations. The study concludes that as the use of pharmacies as
      sources of immunization is expected to continue to expand, pharmacists should
      take these factors into consideration when they decide to offer immunizations.

PMID- 12802975
TI  - The public health function in central and eastern Europe.
AB  - This paper provides a description of the structure and function of public health
      within seven central and eastern European countries. The information was gathered
      from senior figures within public health in these countries, who came together at
      a European Union (EU)-funded seminar on public health which aimed to share recent
      developments in the public health function in their countries, and to develop a
      shared vision of the future for public health across an (eventually) much
      enlarged and united EU. An essential starting point for this was a clear
      understanding of how public health operates within each of the countries
      involved. The information gathered and presented here suggests that the countries
      of central and eastern Europe included in this survey have much in common with
      current EU member states, in that public health is held to be of national
      importance. On the whole, they share similar priorities. The organization of the
      public health function varies quite considerably and variations of degrees of
      central and local control are manifested. There is also variation in the
      relationship between the 'health' and 'environmental' aspects of public health.
      In some countries, these are distinctly separate areas of activity, whereas in
      others they are integrated. All countries acknowledge that public health practice
      is a multidisciplinary activity, but this is not necessarily backed up with
      unified systems for co-ordinated education, training and development, open to
      all. Continued cross-Europe discussion, exchange of information on the
      development of the public health function, and collaboration on training,
      education and development in public health will be of mutual benefit and is
      essential if high standards in public health practice are to be achieved and
      maintained across the whole of the European region.

PMID- 12802976
TI  - Health education: a case for resuscitation.
AB  - Health education is the component of health promotion designed to achieve
      learning related to health or illness. While often described by other names, an
      educational element features in nearly all health promotion activities. Unlike
      most other public health actions, it focuses on voluntarism and frequently on the
      individual. Health education and the resources devoted to it grew rapidly in the
      latter half of the 20th century. However, in the 1970s, many health educators
      started to question its value. They criticized it as being excessively concerned
      with disease, victim blaming, politically naive and increasing health
      inequalities. While promoting knowledge and skills for health was included as one
      of the five principles of health promotion in the World Health Organization's
      Ottawa charter, it received much less attention than the other four principles.
      Health education was also criticized as being ineffective. Methods for evaluating
      health education are hotly contested but there is evidence that some education
      interventions are effective. Current health strategies continue to advocate
      prevention through health education, and workers in many different settings are
      expected to ensure that health education is provided. These front-line educators
      should be able to look to those who specialize in health promotion to support
      their educational activities. This paper argues that the worth of health
      education compared with other forms of health promotion has been grossly
      underestimated and it is time to re-assert its importance.

PMID- 12802977
TI  - Does car ownership reflect socio-economic disadvantage in rural areas? A cross
      sectional geographical study in Wales, UK.
AB  - It is widely believed that area-based deprivation indices that include the car
      ownership census variable are poor indicators of deprivation in rural areas since
      car ownership is a necessity of rural life. In this cross-sectional geographical
      study, we assess whether the relation between lack of car ownership and socio
      economic deprivation varies between urban and rural enumeration districts of
      Wales, UK. We classified the 6376 census enumeration districts in Wales into
      rural (1636, 26%) and urban (4740, 74%), using the Office for National
      Statistics' classification based on land use. Rank correlation coefficients
      between the proportion of households with no car and a range of other proxy
      deprivation census variables were strongly positive in urban and the most densely
      populated rural enumeration districts. However, these correlations were weaker in
      sparsely populated rural enumeration districts, with a declining trend across
      deciles of population density. Exclusion of the car ownership variable from the
      Townsend index of deprivation re-categorized rural enumeration districts as more
      deprived and urban enumeration districts as less deprived compared with the
      standard Townsend index. Our results suggest that lack of car ownership is a poor
      proxy for social deprivation in the most sparsely populated rural areas of Wales,
      and therefore, deprivation indices that include the car ownership variable are
      less valid for use in rural areas.

PMID- 12802978
TI  - An outbreak of Legionnaire's disease among visitors to a fair in Belgium in 1999.
AB  - This paper describes an outbreak of Legionnaire's disease at Kapellen in Belgium
      among visitors of the annual fair. The investigation started on 13th November
      1999 after a respiratory physician notified the health authorities of the
      province of Antwerp of presumptive cases of legionellosis. The annual commercial
      fair at Kapellen, a small town in northern Belgium, was held 10 days previously
      and attracted 50,000 visitors. Stand employees (professionals or volunteers),
      technical staff of the hall and visitors at the fair were affected cases. An
      exploratory case-control study was conducted to trace the source of the epidemic.
      To complete the inventory study and to evaluate other risk factors, a cohort
      study of exhibitors and staff was conducted. Ninety-three people met the case
      definition, 41 of whom were considered as confirmed, 14 as presumptive cases and
      38 as possible/clinical cases. Five people died. Further testing at the reference
      laboratory confirmed all strains to be Legionella pneumophila serogroup 1. The
      sensitivity for culture was low (29.2%), and sensitivity for seroconversion was
      high (90.9%). For urinary antigen test, a sensitivity with Biotest EIA of 65.6%
      was found, and the sensitivity of polymerase chain reaction (PCR) was 85.7%. In
      all cases, the individual had visited the fair. Those individuals working in the
      central areas of the tent, near the aerosol-producing devices, were at higher
      risk of disease. Legionella was detected by PCR on swabs of the surfaces of the
      whirlpool. Although not fully proven, an aerosol-producing device was the most
      probable source of the outbreak.

PMID- 12802979
TI  - An analysis of calls to an out-of-hours palliative care advice line.
AB  - An advice line was set up by a specialist palliative care hospice to improve the
      provision of out-of-hours palliative care to primary care teams, i.e. from 17.00
      to 09.00 h during the week and at weekends and bank holidays. A senior member of
      nursing staff or medical staff answered all calls. During the first year of
      operation, 98 calls were received. The majority of callers were GPs (55%) and
      community nurses (34%). The advice requested was largely related to management of
      pain and the use of opiates, e.g. breakthrough dose of opiates and conversion of
      drugs to syringe drivers. Recommendations from this study include the provision
      of continuing education on management of terminally ill patients, and improved
      communication between primary care teams, providers of out-of-hours primary care
      and specialist palliative care teams.

PMID- 12802980
TI  - Residence, delivery and referral patterns of infants and fetuses with birth
      defects delivered in Hawaii, 1986-1999.
AB  - Information on residence, delivery and referral patterns is useful to a birth
      defects program for allocation of resources, predicting where deliveries may have
      occurred, and estimating the impact of altering geographic inclusion criteria.
      The purpose of this study was to describe the residence, delivery and referral
      patterns for infants and fetuses with birth defects delivered in Hawaii. Data
      were obtained from the Hawaii Birth Defects Program and included birth defects
      cases delivered between 1986 and 1999 with known delivery residence and place of
      delivery. Of 12,873 total cases, 171 (1%) were delivered to out-of-state
      residents. Of the remaining 12,702 cases delivered to residents in the four
      Counties of Hawaii, 9905 (78%) were to City and County of Honolulu residents and
      2797 (22%) were to residents of Hawaii, Kauai and Maui Counties. Of the cases
      delivered to City and County of Honolulu residents, 9903 were delivered in that
      County. Of the cases delivered to residents of the other three Counties, 591
      (21%) were referred to the City and County of Honolulu for delivery, and 1602
      (57%) were referred to the City and County of Honolulu for any reason. Honolulu
      delivery referral rates and total referral rates for cases delivered to Hawaii,
      Kauai and Maui County residents were higher with prenatal diagnosis of a birth
      defect (59 and 87%, respectively) and elective termination (70 and 85%,
      respectively), and varied among 53 different types of birth defect (0-83% and 23
      100%, respectively).

PMID- 12802981
TI  - Rapid assessment of the prevalence of lower limb clinical rickets in Bangladesh.
AB  - This study attempted to measure the prevalence of lower limb clinical rickets
      using a rapid assessment methodology in Cox's Bazaar, a coastal district of
      Bangladesh. The study populations were drawn from 28 random villages representing
      all seven 'thanas' (subdistricts) of the district. Data were collected on 25,891
      children and young people aged 1-20 years in two phases. In the first phase, 30
      trained, local, non-medical people listed 490 children suffering from visible
      signs of any physical disability. To achieve this, they demonstrated a
      multicolored poster showing the features of lower limb clinical rickets to key
      informants in the villages. In the second phase, two teams of medically trained
      people (physicians), each with one male and one female, validated the above cases
      for rickets. They verified and validated 278 cases in five thanas. Due to
      inclement weather and floods, they could not visit the other two thanas. Based on
      these data, the adjusted prevalence rates for lower limb clinical rickets were
      calculated to be 931 per 100,000 population (95% confidence intervals 795-1067).
      The prevalence was highest (1215) in children aged 1-4 years and lowest (498)
      amongst 17-20 year olds. Females had lower prevalence than males. Based on the
      study experience, a quick investigation using a similar methodology was performed
      in five other districts (Sunamganj, Noakhali, Bhola, Jessore and Gaibandha), and
      clinical signs of lower limb rickets were found in Sunamganj and Jessore. It thus
      indicates that rickets may be endemic, not only in Cox's Bazaar but also in some
      other parts of Bangladesh. The methodology used for this study was found to be
      rapid, simple, replicable and inexpensive.

PMID- 12802982
TI  - [External ear melanoma].
AB  - Cutaneous melanomas are the tumours that have increased more their incidence in
      the last fifty years. Melanomas arising from the external auditory canal are
      extraordinariously unfrequent. These tumours show an aggressive and silent
      behaviour, and due to this the diagnosis is frequently made in an advanced stage.
      A male with a malignant melanoma arising from his left external auditory canal
      was attended in our department, suspecting an epidermoid carcinoma. The clinical
      findings and the extension of the lesion required a lateral temporal bone
      resection, parotidectomy and neck dissection to achieve a total resection. We
      present a review of the literature about this entity and an analysis of the
      incidence, significance of the lymph node metastases and value of the elective
      neck dissection.

PMID- 12802983
TI  - [Mastoid osteoma].
AB  - The osteomas of the mastoids are slow growing benign tumors, made predominantly
      of mature bone. Clinically these tumors are asymptomatic, except for cosmetic
      deformities, and they are usually casual radiological findings. Surgical
      treatment is indicated for symptomatic osteomas. In Spain only sixteen cases of
      extracanalicular osteoma have been described in the literature. Two new cases are
      reported and a review of the literature is presented.

PMID- 12802984
TI  - [Technical aspects in endoscopic surgery of frontal mucopyocele].
AB  - The term mucocele is applied to define a chronic, expanding, mucosa-lined lesion
      of the paranasal sinus characterized by mucous retention that can be infected
      becoming a mucopyocele. Until recently the majority of patients with
      frontoethmoidal mucoceles were treated through an external approach, however,
      selected cases of mucoceles can be approached endoscopically, decreasing the
      morbidity associated to external approaches. We report the case of a frontal
      mucopyocele with rapid expansion and erosion of the anterior wall. Surgical
      aspects and postoperative follow-up are described.

PMID- 12802985
TI  - [Unusual presentation forms of Wegener's disease].
AB  - Wegener's granulomatosis may appear with the classic granulomatous necrotizing
      vasculitis affecting both high and low airway and renal glomerule, and rarely
      small vessels in any other location. In this way we may find generalized and
      localized forms of the disease. Three atypical cases of the disease are reported.
      The first one as a limited form with only airway affection. The second one as an
      unusual case of otitis with progressive affection of I, II, V, VI, VII and VIII
      cranial nerves. The third one was a generalized case with sinusitis and orbital
      pseudotumor. Both first and second cases have been controlled for a very long
      period of time of 22 and 14 years respectively, and none of them has presented
      any other location of the disease.

PMID- 12802986
TI  - [Upper dysphagia due to a chemotherapy resistant Burkitt's lymphoma in a lingual
      tonsil].
AB  - The higher incidence of immunosuppressive status is increasing in the last years
      the diagnosis of tumours of unusual location and behaviour. We present the case
      of a HIV-seropositive 41 years-old woman, bearing of high dysphagia and
      pharyngolalic voice. The exploration showed a tumour emerging in lingual tonsil
      and spreading out to hypopharynx and larynx. No lymph nodes were observed. Its
      resistance to chemotherapy made necessary its surgical removal.

PMID- 12802987
TI  - [Laryngeal sarcoidosis: a case report].
AB  - Sarcoidosis is a chronic multisystemic granulomatosis of unknown etiology that
      affects mainly young adults. It characterized by bilateral hiliar adenopathies
      interstitial pulmonary infiltrate, and cutaneous and ocular lesions. Localization
      in upper respiratory tract is infrequent. In the present report we describe a 26
      year-old male with a three-month history of a globus sensation, hoarse voice,
      loud snoring and obstructive sleep apnoea, because of a laryngeal noncaseating
      granulomatous infiltration. The diagnosis is made through the history, the
      radiology and the pathological examination. Treatment is symptomatic, due to its
      tendency to a spontaneous regression. The treatment is based on corticosteroids
      by systemic or aerosol routes. Micro surgical excision and tracheotomy may be
      useful in selected patients.

PMID- 12802988
TI  - [Laryngeal chondro-radionecrosis].
AB  - Laryngeal chondroradionecrosis is a complication following radiotherapy for
      laryngeal tumours that may appear many years after the treatment. We present the
      case of a 78 year old man, that come to the Accident and Emergency department
      with a prelaryngeal mass and hemoptysis. He had been treated 17 years before with
      radiotherapy for a vocal cond carcinoma. Posteriorly the lesion did a cutaneous
      fistula with complete laryngeal exposition and torpid evolution. Post
      radiotherapy necrosis in the larynx is a serious complication though not a common
      one. A tumour recurrence needs to be excluded and even in this case a total
      laryngectomy is mandatory as it will end in total loss of laryngeal function.

PMID- 12802989
TI  - [Parotid tuberculosis following intravesical BCG instillation: a case report].
AB  - First case of parotid gland tuberculosis publicated to date is presented after
      intravesical instillation of BCG for a superficial bladder cancer. The diagnosis
      of the parotid gland tuberculosis is difficult because it is usually
      indistinguishable from a neoplasm. Combined fine-needle aspiration cytology with
      PCR or LCR amplification of mycobacterial DNA could be a good diagnostic tool
      avoiding an open biopsy.

PMID- 12802990
TI  - [Thyroid actinomycosis: a case report].
AB  - Actinomycosis is nowadays a not very common festered chronic infection.
      Cervicofacial actinomycosis is the most frequent clinical form, and it is due in
      most cases to Actinomyces israelii. Thyroid actinomycosis has been scarcely
      described in the literature. The lesions, that are characterized to be notably
      indurated and to contain multiple abscesses that drain to the surface through
      sinus tracts, frequently simulate other infective clinical entities and often
      neoplasms, therefore the diagnosis is delayed in the time. From a case of thyroid
      actinomycosis diagnosed and treated in our service which was initial diagnosed as
      a thyroid neoplasm, we revise the cases described in the literature and we make a
      point in the difficulty to arrive to the diagnosis of this entity.

PMID- 12802991
TI  - [Hibernoma: a rare case of cervical mass].
AB  - The hibernoma is an uncommon benign tumor thought to arise from the vestiges of
      the fetal brown fat. The term hibernoma is derived from the microscopic
      similarity of this tumor to the glandular brown adipose tissue occurring in the
      organs of hibernation of certain animal species. There are reported about 100
      hibernomas in the literature world wide and only a small number of them are in
      the neck. We report the case of a 33 years old male with a 20 months history of a
      painless mass in his right neck.

PMID- 12802992
TI  - [Spontaneous cervical emphysema and pneumomediastinum with voice disorders].
AB  - Spontaneous cervical emphysema and pneumomediastinum, occurring in the absence of
      previous disorders or provocating factors, is very rare. The predominant symptoms
      are retroesternal pain, dyspnea, dysphagia and neck pain. The diagnosis is
      established radiologically. The evolution is generally good and conservative
      therapy leads to recovery in most patients. We present an unusual case of
      pneumomediastinum, cervical and retropharyngeal emphysema that spread to cavum;
      the suspected symptom was voice alteration as reported by the parents.

PMID- 12802994
TI  - [A little bit of history].

PMID- 12802993
TI  - [Consequences of the bilateral vagus nerve section at a cervical level].
AB  - We present the consequences corresponding to a bilateral section of the main
      trunk of vagus nerve at cervical level in a patient with an oropharyngeal
      carcinoma with bilateral neck nodes. As a consequence of the bilateral resection
      of both vagus nerves during neck dissections, as well as motor and sensitive
      damage of the larynx and pharynx, we could observe affection of the normal tone
      of the oesophagus, stomach and duodenum which forced to enteral nutrition by
      direct jejunal access, and a disorder of the cardiac rhythm due to loss of the
      parasympathetic innervation appeared.

PMID- 12802995
TI  - [Vital anxiety and its treatment. 1953].

PMID- 12802996
TI  - [Differential diagnosis: a difference between depressive manic disorder and
      catatonia. 1924].

PMID- 12802997
TI  - [Psychoanalytical data in a case of obsessive doubt. 1923].

PMID- 12802998
TI  - [On cataplexy and particularly on cataplexy in wakefulness. 1928].

PMID- 12802999
TI  - [Constitution factors and their revealing value in the analysis of behavior
      disorders. 1927].

PMID- 12803000
TI  - [The Salpetriere school: J.M. Charcot, psycho-physiologist. 1950].

PMID- 12803001
TI  - [Practical psychotherapy. General fundamentals. 1952].

PMID- 12803002
TI  - [The treatment of the writer's cramp by relaxation (the process of healing from
      the beginning of the relaxing experience). 1956].

PMID- 12803003
TI  - [Lithium in psychiatry. I. Therapeutic and preventive properties. 1971].

PMID- 12803004
TI  - [Animal neuroses and human psychiatry. 1957].

PMID- 12803005
TI  - Surgical anatomy of the thyroid and parathyroid glands.
AB  - From a surgical viewpoint there are several critical anatomic structures that lie
      in close proximity to the thyroid gland. These critical structures include the
      recurrent laryngeal nerves, the superior laryngeal nerves, and the parathyroid
      glands. Successful thyroid surgery depends on the technical skill of the surgeon
      to identify and preserve these vital structures.

PMID- 12803006
TI  - Thyroid physiology and thyroid function testing.
AB  - The art and science of medicine has changed so much in the last 40 years, not
      only in the manner that physicians treat medical diseases but also in how they
      diagnose them. Technological advances have made it possible to have a test for
      almost anything. These technological advances, however, are important
      contributing factors to the rising cost of healthcare. More than ever, cost
      containment is an important element in all aspects of patient care. Minimizing
      costly diagnostic imaging and laboratory tests is essential in keeping healthcare
      costs reasonable but these tests should not be excluded at the risk of
      compromising patient care. For patients with thyroid disorders, the multiplicity
      of tests available do not make diagnoses more accurate or treatment more
      effective. A single test, the sensitive thyrotropin assay, most eloquently allows
      an organized, streamlined approach to the diagnoses and management of patients
      with thyroid disease. Even the most technologically advanced tests that are
      available cannot replace the clinical skills of the physician. Clinical acumen
      combined with the judicious use of diagnostic testing is one of the most
      important elements in diagnosing and treating a patient.

PMID- 12803007
TI  - Evaluation of a thyroid nodule.
AB  - Solitary thyroid nodules are common entities and the majority of these are
      benign. The main goal in evaluating these nodules is to identify the [figure: see
      text] nodules with malignant potentials. A multitude of diagnostic tests is
      available to the clinician. FNA biopsy is now considered the gold standard
      diagnostic test in the evaluation of a thyroid nodule. Ultrasound and nuclear
      scans are also useful tests, but are best used in conjunction with FNA. Clinical
      decisions are often based on the results of the FNA. A diagram of the clinical
      decision process based on FNA findings is presented in Fig. 1. Despite the
      clinical advantages that are provided by the FNA results, the clinician should
      not dismiss the importance of other clinical prognostic indicators to optimize
      timely treatment.

PMID- 12803008
TI  - Multinodular goiter.
AB  - MNG is a common clinical problem. Though most goiters are benign and
      asymptomatic, they may cause concern when they create compressive symptoms,
      develop autonomous functioning nodules, or form suspicious nodules. Diagnostic
      evaluation should include clinical evaluation, laboratory tests including TSH,
      and consideration of additional evaluation and imaging when there exists
      suspicion of complicating factors or risk of malignancy. In nontoxic MNG,
      suppression therapy or serial clinical exams and TSH values are appropriate in an
      asymptomatic, nonsuspicious goiter. In toxic MNG, treatment of the resulting
      thyrotoxicosis followed by RAI or surgery is indicated. When compressive
      symptoms, risk of malignancy, or cosmetic deformity develops, surgery also may be
      indicated.

PMID- 12803009
TI  - Inflammatory thyroid disorders.
AB  - Inflammatory thyroid disorders encompass a broad spectrum of diseases that are
      generally self-limited, and relatively easy to diagnose and manage. Autoimmune
      subtypes are by far the most commonly encountered diagnoses and create the most
      confusion because of simultaneous overlap and the potential for interconversion
      among the subtypes. The otolaryngologist will frequently see these disorders and
      provide valued consultative care and surgical intervention as needed.

PMID- 12803010
TI  - Well-differentiated carcinoma of the thyroid.
AB  - Thyroid cancer will be diagnosed in more than 20,000 individuals in the United
      States in 2002. Approximately 16,000 of these patients will be women. During the
      same year, an estimated 1300 deaths from thyroid cancer are expected. The various
      types of thyroid cancer include papillary carcinoma, follicular carcinoma,
      Hurthle cell carcinoma, medullary carcinoma, anaplastic carcinoma, and thyroid
      lymphoma. Papillary, follicular, and Hurthle cell carcinoma are considered well
      differentiated thyroid cancers and constitute the focus of this article.

PMID- 12803012
TI  - Rare tumors of the thyroid gland.
AB  - Although the vast majority of thyroid cancers are well-differentiated and carry
      an excellent prognosis, several rare tumors occasionally involve the thyroid
      gland and require unique treatment paradigms. Anaplastic carcinoma of the thyroid
      is an extremely aggressive neoplasm that is generally best managed with surgery
      followed by a multimodality regimen of radiotherapy and chemotherapy. Squamous
      cell carcinoma of the thyroid often mimics the clinical course of anaplastic
      carcinoma and is best treated with aggressive surgery followed by postoperative
      radiotherapy. Treatment and prognosis of lymphoma of the thyroid varies depending
      upon the specific pathological subtype, with combination chemotherapy and
      radiation therapy used primarily. Sarcomas of the thyroid are primarily managed
      with surgery, although radiation and chemotherapy are indicated in some cases.

PMID- 12803011
TI  - Medullary thyroid cancer.
AB  - Medullary thyroid cancer is a rare neoplasm that arises from the parafollicular C
      cells. It occurs in a sporadic form, or less commonly as a hereditary form, as
      part of multiple endocrine neoplasia syndromes types 2A and 2B. The RET proto
      oncogene is currently the primary factor that is implicated in the hereditary
      forms of this neoplasm. The knowledge about the genetic makeup of the neoplasm
      impacts upon management as it allows for screening, early detection, and
      prophylactic treatment. Surgery is the main modality that offers a cure. This
      entails a total thyroidectomy and vigilant management and surveillance of the
      neck. Prognosis of patients with MTC is variable, but the more constant factors
      that affect it are the stage of disease and the age of the patient. The emerging
      molecular genetic understanding of this malignancy will provide the foundation
      for prognostic and therapeutic decision-making in the future. Interdisciplinary
      management by surgeons, endocrinologists, pathologists, radiotherapists,
      radiologists, and medical oncologists should be sought.

PMID- 12803014
TI  - Postoperative management of differentiated thyroid cancer.
AB  - The large numbers of studies on the postoperative management of differentiated
      thyroid carcinoma allows us to use adjuvant treatment and follow-up studies more
      selectively based on patient risk for recurrence and mortality. Recurrent
      differentiated thyroid carcinoma is more easily and more effectively treated with
      early diagnosis. With this in mind, patients who are at high risk for life
      threatening recurrent disease should be treated aggressively and followed up
      expectantly. In these patients, adjuvant treatment with 131I ablation and thyroid
      hormone suppression is appropriate. External irradiation may be considered,
      especially for patients with postoperative residual disease. Close follow-up with
      stimulated thyroglobulin and 131I whole body scans should be performed to
      facilitate early detection of recurrent disease. Low-risk patients may be
      effectively treated with more conservative management. 131I ablation has not
      resulted in improved survival in these patients. Follow-up with serum
      thyroglobulin after initial negative 131I whole body scan may be appropriate in
      these patients. Management of patients at intermediate risk remains
      controversial. Recombinant human thyrotropin allows us to obtain stimulated serum
      thyroglobulin and promises the ability to perform 131I ablation and whole body
      scan without the need for thyroid hormone withdrawal. Functional radionuclide
      imaging, such as FDG PET, now allows us to localize recurrent disease in patients
      with elevated serum thyroglobulin but negative 131I scan.

PMID- 12803013
TI  - Evaluation and management of a solitary thyroid nodule in a child.
AB  - Although an uncommon clinical entity, a pediatric patient with a solitary thyroid
      nodule requires a thorough assessment because of the increased incidence of
      thyroid carcinoma in this population. In the future, one may expect the
      widespread clinical use of genetic markers in identifying children, who are at
      risk for, or who have developed, thyroid carcinomas, with the hopes that these
      molecular markers will lead to the prevention, or earlier detection and cure, of
      these malignancies.

PMID- 12803015
TI  - Surgical considerations and controversies in thyroid and parathyroid surgery.
AB  - The techniques of thyroid surgery have been fully elucidated in several surgical
      texts and atlases. This article discuss surgical pearls of thyroid and
      parathyroid surgery. We discuss preoperative, intraoperative, and postoperative
      considerations and controversies for both procedures.

PMID- 12803016
TI  - Complications of thyroid and parathyroid surgery.
AB  - Today most complications of thyroid and parathyroid surgery are related to either
      metabolic derangements or injury to the recurrent laryngeal nerves. Other
      complications include superior laryngeal nerve injury, infection, airway
      compromise, and bleeding. Although the principal goal of thyroid and parathyroid
      surgery is the prevention of these complications, prompt recognition and
      intervention will minimize morbidity and provide the patient with the best chance
      of a satisfactory outcome.

PMID- 12803017
TI  - Current issues in hyperparathyroidism.
AB  - There has been a shift in the referral patterns in recent years that has resulted
      in increasing numbers of patients being referred to surgeons with a diagnosis of
      hypercalcemia rather than primary hyperparathyroidism. The surgeon must perform a
      thorough history, including medications, and laboratory assessment, including
      serum calcium and parathyroid hormone measurements. A 24-hour urinary calcium
      excretion should be routinely ordered to exclude FHH. After the diagnosis of
      primary hyperparathyroidism is made, preoperative localization studies will
      benefit 78% to 90% of patients, with sestamibi scan being the most commonly used.

PMID- 12803018
TI  - Surgical management of the parathyroids.
AB  - The recent advance of intraoperative PTH monitoring combined with preoperative
      localization techniques allow for minimally invasive parathyroid surgery in 75%
      to 85% of cases. In cases where a single adenoma is identified, minimally
      invasive techniques should result in a need for repeat surgery in only 2% of
      cases. The cost of intraoperative PTH assays of localization and gamma probes
      limits their availability. Complications of parathyroidectomy are uncommon, but
      appropriate management is important, particularly for patients with hypocalcemia.

PMID- 12803019
TI  - [Caring for a often marginalized population].

PMID- 12803020
TI  - Hospitals face their own insurance crisis.

PMID- 12803021
TI  - This Forbes' magazine is loaded for combat.

PMID- 12803022
TI  - JCAHO to begin all-random hospital inspections in 2006.

PMID- 12803023
TI  - Sleeping with the enemy: understanding and influencing physician behavior.

PMID- 12803024
TI  - Improving the strategic value of hospital-owned practices.

PMID- 12803025
TI  - FDA proposes new rules that would require barcoding and new reporting procedures.

PMID- 12803026
TI  - Exploring a new alternative to hospital/physician joint ventures.

PMID- 12803027
TI  - Hospital/physician collaboration strategies in radiology.

PMID- 12803028
TI  - Transforming healthcare quality.

PMID- 12803030
TI  - Imaging in the second century: the introduction of functional imaging.

PMID- 12803029
TI  - A medical student is elected to the presidency.

PMID- 12803031
TI  - Positron emission tomography (PET): the basics.

PMID- 12803032
TI  - PET: oncological applications.

PMID- 12803033
TI  - Neurologic PET.

PMID- 12803034
TI  - Cardiac applications of positron emission tomography (PET).

PMID- 12803035
TI  - Future advances and applications in positron emission tomography.

PMID- 12803036
TI  - Certificate of need process: an assessment of the need for PET.

PMID- 12803037
TI  - Damp housing conditions and asthma in Rhode Island.

PMID- 12803038
TI  - The verbiage of obesity.

PMID- 12803039
TI  - Testing your diagnostic skills. Case no. 1. Odontogenic keratocyst.

PMID- 12803040
TI  - Testing your diagnostic skills. Case no. 2. Granular cell tumor.

PMID- 12803041
TI  - Members help needy children, make outreach program a success.

PMID- 12803042
TI  - Volunteers create healthy smiles during special day of giving.

PMID- 12803043
TI  - [L-Glutamate oxidase from Streptomyces cremeus 510 MGU: effect of nitrogen
      sources on enzyme secretion].
AB  - Effect of nitrogen sources (organic complexes and mineral salts) on L-glutamate
      oxidase synthesis by Streptomyces cremeus 510 MGU was studied. Optimal enzyme
      production was not provided by any single nitrogen source. The most effective
      combination of nitrogen sources (soy flour, peptone, ammonium sulfate) was
      elaborated by the mathematical planning method. The results of experiment allowed
      to enhance biosynthesis of extracellular L-glutamate oxidase to 2.4-2.6 U/mL. It
      was shown that L-glutamate oxidase of Streptomyces cremeus 510 MGU is highly
      specific to substance and is stable during storage of filtrated culture with pH
      6.8-9.0.

PMID- 12803045
TI  - [Antagonistic activity of lactic acid bacteria against pathogens localized
      outside the gastrointestinal tract].
AB  - Our research has proved that lactic acid bacteria possess the wide spectrum of
      antimicrobial activity. They inhibit the growth of not only agents of intestinal
      infections but also diseases located outside the gastrointestinal tract.

PMID- 12803044
TI  - [Effect of fosfidomycin on development of various infections in mice].
AB  - Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of
      isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a
      certain protective effect on mice experimentally infected with tularemia, tiphus
      or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was
      not observed when the animals were given 1 mg of fosmidomycin per capita twice a
      day. Under oxidative conditions an ESR signal of long living nitroxil free
      radicals were registered in the water solution of fosmidomycin. The radicals are
      supposed to be involved in the therapeutic effect of the antibiotic.

PMID- 12803046
TI  - [Itraconazole (Orungal) in the treatment of mycotic infections in oncologic
      patients].
AB  - Clinical and microbiological activity of itraconazole (Orungal, solution for oral
      use, "Janssen-Cilag") for treatment of oncological patients with inhospital
      infections associated with candida was evaluated. The trial included 50 patients
      with oncological pathology of respiratory tract, as representatives of risk group
      for candida contamination. Two groups of patients were formed: when candida
      contamination was proved patients of the test group were treated by antifungal
      agent itraconazole (Orungal, "Janssen-Cilag"). Patients in control group were
      treated by fluconazole (Diflazon, "KRKA") according to standard therapy regime.
      When no clinical efficacy was achieved patients in both groups were treated by
      amphotericin B (Fungizone, "Bristol-Myers Squibb"). Clinical efficacy was
      demonstrated at 13 patients and microbiological efficacy (pathogen elimination)
      at 12 patient of 14 of itraconazole group. Clinical efficacy was demonstrated at
      9 patients and microbiological efficacy at 7 of 11 patients of fluconazole group.
      Treatment with amphotericin B was effective at all 4 patients treated with this
      antibiotic, microbiological effect was demonstrated for 3 patients of the group.
      Frequency of side effects was significantly less in itraconazole group. The
      course price was also significantly lower at itraconazole group. All this data
      are important for elaboration of optimal pharmaco economic policy regarding
      inhospital infections at critical care units.

PMID- 12803047
TI  - [Azithromycin: general properties and regimen optimization based on
      pharmacokinetic and pharmacological parameters].

PMID- 12803048
TI  - [Membranotropic compounds and preparations affecting earlier stages of HIV
      infection].

PMID- 12803049
TI  - [Severe acute respiratory syndrome (SARS)].
AB  - On November 2002, 305 cases of atypical pneumonia appeared in southern China. In
      February 2003, cases were reported in Hong Kong and from there the disease spread
      to many other countries, mainly, China, Hong Kong, Singapore, Vietnam and Toronto
      in Canada. The syndrome was defined as Severe Acute Respiratory Syndrome SARS),
      and a person is suspected of having SARS if he/she became ill after November 1
      2002, has a fever exceeding 38 degrees C, has symptoms of a respiratory disease
      and was in a risk area or in close contact with a SARS patient within ten days
      prior the appearance of symptoms. The World Health Organization has received
      reports of 4,836 cases, of which 293 persons have died. Most were family members
      or medical staff treating the patient, persons who came into close and prolonged
      contact with the patient. The estimated incubation period is two days to one
      week. Symptoms of the disease include fever, shortness of breath and cough. Ten
      percent of patients afflicted with SARS require artificial breathing. The
      mortality rate is 6-7%. A novel coronavirus is associated with this outbreak, and
      the evidence indicates that this virus has an etiologic role in SARS. Infection
      is transmitted from person to person through direct or close contact with
      airborne droplets or personal objects of an infected person. Patients must be
      isolated and treated by contact and airborne isolation. Treatment consists of
      support care and artificial respiration when required. The use of anti-viral
      medications has not yet proven effective.

PMID- 12803050
TI  - [Why viral (SARS, Ebola and AIDS) epidemics now?].
AB  - In the last three decades we have seen several viral (and bacterial; i.e. TB)
      epidemics which took place at an era where we would have expected the eradication
      of many infectious diseases. There are many hypotheses to explain this paradox;
      1) Is it the hygiene theory, namely extensive use of wide spread and too potent
      antibiotics which eliminate protective infecting agent? And hence the beneficial
      effect of probiotics? Is it the widespread use of vaccine? Is it a mistake or a
      terror acts of leakage of viral mutant from research or other laboratories? Be it
      as it may, the globalization and the employment of long distance flights make the
      spread easy to extreme points in the globe (Shanghai-Toronto). The new
      epidemiology? Immunology fields will have to deal with these novel aspects to
      combat and to prevent more events.

PMID- 12803051
TI  - [Laparoscopic anterior lumbar interbody spinal fusion].
AB  - The technique of Laparoscopic Anterior Lumbar Interbody Spinal Fusion (ALIF) has
      been developed in recent years for treating patients with spondylolisthesis,
      symptomatic degenerative disc disease and as salvage for failed posterior spinal
      fusion. The authors have performed 23 laparoscopic ALIF procedures with the close
      cooperation of spine and laparoscopic surgeons. This collaboration resulted in
      the successful laparoscopic completion of 87% of our cases. Postoperative length
      of stay was 2 days and patients required only minimal amounts of oral pain
      medications. Fourteen patients (70%) achieved excellent long term pain relief
      while 3 patients subsequently required an additional posterior fusion. There was
      only one major complication of bleeding from an ileac vein. Our results, similar
      to the results published by others, demonstrate the feasibility and effectiveness
      of laparoscopic ALIF. Further proof is still necessary to determine whether this
      procedure carries significant advantages vis-a-vis the open anterior or
      retroperitoneal approach.

PMID- 12803052
TI  - [Thiamine deficiency among Chinese workers in Israel].
AB  - The death of a 23-year-old Chinese construction worker in southern Israel from
      refractory metabolic acidosis after presenting symptoms of edema and loss of
      sensation in his legs raised the suspicion of Beriberi disease. As thiamine
      deficiency was suspected, two other Chinese workers from the same construction
      site, who also complained of pain and swelling in their legs were tested and
      found to have a significant deficiency. In addition 56.5% of 46 Chinese workers
      at the site were found to have a thiamine deficiency without any significant
      clinical symptoms. A nutritional evaluation demonstrated a lack of thiamine in
      the workers diet due to a limited variety of food, their dietary preferences, and
      cooking style. There was also a lack of attention given to providing essential
      nutrients including thiamine by their employees. Clinicians must be aware that
      thiamine deficiency and beriberi disease may be common in this apparently healthy
      population.

PMID- 12803053
TI  - [Complaints in mental health services in Israel: a one year-study].
AB  - Despite the growing awareness of mental patients of their rights, the number of
      complaints is still under-represented for different reasons including the
      patients' fear that they will be 'punished' because of their complaints or their
      lack of knowledge concerning the correct procedure and the appropriate address
      for issuing their complaint. This article presents the summary of one year's work
      (year 2001), on the complaints and letters we received at the Forensic Psychiatry
      Unit, Mental Health Services, Ministry of Health, from the general public, mental
      health patients, their families or Advocacy Agencies concerning mental patients'
      rights. We analyzed the complaints according to the topic, the process and the
      results of our interventions. The data collected on the complaints show that most
      of the complainants were the patients themselves, especially males and adults.
      Most of the complaints dealt with the patients' dissatisfaction with the type of
      treatment received, in that it did not match their expectations. Fifty percent of
      the complaints involved treatment received at psychiatric hospitals and 34% of
      the complaints were related to out-patient treatment. Sixty-five percent of
      complainants wrote a single complaint during the year 2001. Our intervention and
      reply to the complainants was completed within a month in 66% of the cases. We
      conclude suggesting different ways to improve this important service.

PMID- 12803054
TI  - [Pyogenic liver abscess--an unusual presentation of colonic villous adenoma].
AB  - A pyogenic liver abscess is a final common pathway of many pathologic processes,
      mainly suppurative cholangitis or suppurative pyephlebitis, arising from
      abdominal or pelvic infection. There are many other etiologies, and some
      abscesses are idiopathic-namely, cryptogenic abscess. We present a case of a man
      with a pyogenic liver abscess. This was the clue for the diagnosis of a large but
      clinically silent villous adenoma of the colon. Colonic tumors, manifested
      clinically as an hepatic abscess, in the absence of liver metastases, are very
      uncommon. This is the first description of a villous adenomatous tumor with such
      a presentation.

PMID- 12803055
TI  - [Driver drowsiness--are physicians at a special risk?].
AB  - BACKGROUND: Sleepiness at the wheel is the main cause of approximately a fifth of
      road traffic accidents. The driver will often feel drowsy before the accident,
      therefore preventive measures can be taken in order to stay alert. AIM: To
      estimate sleepiness among sleep deprived drivers and to explore methods they use
      to stay alert. METHODS: We choose three professions at increased risk of
      sleepiness: physicians working night shifts, night shift nurses and hi-tech
      workers who work 12 hours or more a day at least twice a week. The subjects
      answered an anonymous questionnaire concerning past involvement in road accidents
      or "near misses", known risk factors for road accidents and methods used to fight
      sleepiness, as well as some demographic data. RESULTS: A total of 115 drivers (38
      physicians, 37 nurses and 40 hi-tech workers) participated in this study. The
      average age was 36.0 + 7.9 years and 53% males. Thirteen percent had been
      involved in road accidents as drivers in the last year, 53% of them remember that
      the accident was due to sleepiness or fatigue. Thirty-seven percent remember at
      least one occasion of "near accident" due to sleepiness. Driving in the
      "dangerous" hours was positively associated with "near accidents" (69% vs. 29%, p
      < 0.001) and in accidents (17% vs. 11% P = NS). Physicians were involved in "near
      accidents" (p < 0.005) more often. The most frequent methods used to overcome
      sleepiness were: listening to the radio (86.1%), opening the window (65.2%) and
      turning on the air conditioning in the car (57.4%). CONCLUSION: Driving whilst
      sleepy is an important contributor to road accidents. It seems that sleep
      deprived workers and especially physicians working in shifts, are at an increased
      risk. This issue should receive a higher priority as part of preventive medicine
      among physicians themselves and their patients.

PMID- 12803056
TI  - [The effect of time on the perception of dyspnea following inhaled long-acting
      bronchodilator].
AB  - STUDY OBJECTIVES: To assess the effect of time on the change in the perception of
      dyspnea (POD) following inhalation of long-acting bronchodilator. PATIENTS AND
      METHODS: Spirometry and the POD were measured in 32 asthmatic patients, with
      moderate asthma, before and following inhalation of placebo, and salmeterol. The
      POD was measured while breathing against progressive loads, using a visual
      analogue scale (VAS). RESULTS: The highest FEV1 levels and the lowest POD were
      measured one hour after salmeterol inhalation. Although the mean FEV1 remained
      close to its peak value for at least six hours following the inhalation of
      salmeterol, there was a gradual statistically significant increase in the POD.
      CONCLUSIONS: Following inhalation of long-acting bronchodilator (LABD) there is
      relationship between the increase in the FEV1 and the decrease in POD. With time
      there is a gradual increase in the perception of dyspnea regardless of the FEV1.

PMID- 12803057
TI  - [Clinical manifestations of "Hunger Disease" among children in the ghettos during
      the Holocaust].
AB  - The harsh life in the ghettos were characterized by overcrowding, shortage of
      supplies (e.g. money, sanitation, medications), poor personal hygiene, inclement
      weather and exhaustion. Under these conditions, morbidity was mainly due to
      infectious diseases, both endemic and epidemic outbreaks with a high mortality
      rate. The dominant feature was hunger. Daily caloric allowance was 300-800, and
      in extreme cases (i.e. Warsaw ghetto) it was only 200 calories. The food was
      lacking important nutrients (e.g. vitamins, trace elements) leading to protean
      clinical expression, starvation and death. The clinical manifestations of
      starvation were referred to as "the Hunger Disease", which became the subject of
      research by the medical doctors in the ghettos, mainly in the Warsaw ghetto in
      which a thorough documentation and research were performed. The first victims of
      hunger were children. First they failed to thrive physically and later mentally.
      Like their elders, they lost weight, but later growth stopped and their
      developmental milestones were lost with the loss of curiosity and motivation to
      play. The mortality rate among babies and infants was 100%, as was described by
      the ghetto doctors: "when the elder children got sick, the small ones were
      already dead...". In the last weeks of the ghettos there were no children seen in
      the streets. In this article the environmental conditions and daily life of
      children in the ghettos are reviewed, and the manifestations of "Hunger Disease"
      among them is scrutinized.

PMID- 12803058
TI  - [Glycoprotein 2b3a inhibitors for acute coronary syndromes: what the trials tell
      us].
AB  - Glycoprotein 2b3a inhibitors represent a promising class of antiplatelet
      medications. Their use in acute coronary syndromes and in patients undergoing
      percutaneous coronary intervention has been the subject of a number of large
      controlled trials, including tens of thousands of patients. These trials examined
      their efficacy, the difference between the various agents, their influence on
      thrombotic events, whether it is justified to use them in patients with acute
      coronary syndromes, and the relationship between these medications and early
      versus aggressive intervention. Platelet GP 2b3a receptor inhibitors seem to have
      a larger effect in patients who have had a primary coronary intervention than in
      those with acute coronary syndromes. In patients with acute coronary syndromes,
      treatment should probably be limited to those considered at high risk: recurrent
      angina, dynamic ST segment changes, or elevated troponin values. The use of
      GP2b3a receptor inhibitors during angioplasty and in patients with acute coronary
      syndromes decreases mortality and the incidence of myocardial infarction, but
      increases the risk of bleeding.

PMID- 12803059
TI  - [Functional transcranial Doppler].
AB  - Transcranial Doppler is an ultrasonic technique, which demonstrates the blood
      flow velocity in the intracranial arteries. Functional Transcranial Doppler
      (fTCD) is a method of comparing the cerebral blood flow velocities of different
      arteries demonstrated simultaneously in both hemispheres. The examination is
      performed before and after fulfilling certain motor and sensory functions and
      execution of cognitive tasks. The rationale behind this method is discussed as it
      is applied in each of those functions. It must be stressed that there is a
      different role of the fTCD in the anterior vs the posterior circulation systems.
      Whereas many studies prove good efficacy with use of middle cerebral artery and
      anterior cerebral artery method, the role of the vertebrobasilar system method is
      unclear. In addition, although visual functions can be demonstrated well by
      examination of the posterior cerebral arteries, only few evidences of efficacy
      were published concerning vertebral and basilar artery functions. However, fTCD
      is useful, easy to perform and presents a very cost effective method for
      demonstration of cerebral blood flow changes during and after completing
      cognitive and motor tasks. The tests can be used in healthy persons, as well as
      in patients with neurological diseases and during rehabilitation period.

PMID- 12803060
TI  - [Application of Ilizarov method in maxillofacial treatment].
AB  - Distraction osteogenesis is becoming the treatment of choice for the surgical
      correction of hypoplasias of the maxillofacial skeleton. The mandible can be
      elongated by intraoral or extraoral devices. The intraoral devices are smaller,
      do not leave an external scar and do not cause social inconvenience to the
      patient. The main disadvantages are less control of vector and the need for a
      second operation for removal. The most important factors of mandibular
      distraction are planning of distraction, location of the osteotomy, control of
      vector of lengthening and type of distraction device. In the maxilla, our
      experience with three types of maxillary distraction is discussed: 1) the rigid
      extraoral distraction, 2) the surgically assisted protraction and 3) the
      intraoral method. In the last years, distraction osteogenesis was applied in the
      treatment of obstructive sleep apnea. The method has several advantages over
      other methods, mainly in treatment of young children in order to improve airway
      and to decannulate tracheostomy. Alveolar distraction osteogenesis poses a new
      challenge in reconstructing atrophic alveolar bone with no need to harvest bone
      graft or to use bone substitutes. The advantages and problematic issues of
      alveolar distraction such as vector control of distraction are described. The
      intraoral method should always be considered first. However, in severely
      hypoplastic patients, when three-dimensional correction is necessary, the
      extraoral device has an advantage over the intraoral device. In the future, the
      issues to consider will be improvement of osteotomies by endoscopy, development
      of smaller multidirectional devices, improvement of bone quality by cytokines and
      growth factors in order to shorten the time of device bearing by the patients.

PMID- 12803061
TI  - [Jimson weed poisoning].
AB  - Datura stramonium abuse causes a potentially lethal anticholinergic intoxication.
      Today, with the internet widely available, our youth are potentially exposed to
      partial and quite often dangerous information that systematically disregards the
      danger of Datura use. The authors suspect that without educational efforts
      regarding the dark side of Datura use, we shall see a rise in poisoning by this
      dangerous substance. This review outlines the general management of the
      intoxication.

PMID- 12803062
TI  - [Can MR angiography (MRA) replace conventional diagnostic angiography?].
AB  - Magnetic Resonance Angiography (MRA) is a reliable and accurate tool for imaging
      the vascular tree. In the current state of the art, most of the vascular
      pathologies can be accurately diagnosed by MRA using MR machines equipped with
      very fast pulse sequences and highly sensitive gradients. This modality can
      replace conventional angiography and the use of iodine, thus reducing the
      morbidity of invasive iodinated contrast based procedures.

PMID- 12803063
TI  - [E-commerce of pharmaceuticals].
AB  - The emergence of the Internet as a new communications and information technology
      caused major social and cultural changes. The dramatic increase in accessibility
      and availability of information empowered the consumer by closing the information
      gap between the consumer and different suppliers. The objective of this article
      is to review many new internet-supported applications related to the
      pharmaceutical market. E-commerce is divided into two major components: Business
      to Consumer (B to C), and Business to Business (B to B). The main applications in
      B to C are dissemination of medical and drug information, and the sale of drugs
      through the Internet. Medical information on the Internet is vast and very
      helpful for patients, however, its reliability is not guaranteed. Online
      pharmacies increase the accessibility and availability of drugs. Nevertheless,
      several obstacles such as security of the data provided (both financial and
      clinical) prevent the widespread use of online pharmacies. Another risk is the
      health authorities' inability to regulate Internet sites effectively. Therefore,
      unregulated sale of prescription drugs, fake or substandard, often occurs on the
      Internet. B to B relates to physicians, clinics, hospitals, HMO's and
      pharmaceutical companies. There is a vast number of applications ranging from
      clinical research, marketing and sales promotion, to drug distribution and
      logistics. In conclusion, the Internet is dynamic and has contributed to the
      development of numerous new applications in the field of pharmaceuticals.
      Regulatory authorities should be active in developing new policies that will deal
      with those new Internet-based applications.

PMID- 12803064
TI  - [Thyroid orbitopathy].
AB  - Thyroid Orbitopathy (T.O) is the most common orbital disease caused by a systemic
      illness. The clinical manifestations of T.O are a result of inflammation, edema
      and scarring of orbital tissue, and include exophthalmos, soft tissue edema, lid
      retraction, chemosis, exposure keratitis that can lead to corneal ulceration and
      perforation, ocular motility disorders and strabismus, and compressive optic
      neuropathy. T.O is an autoimmune disease but the exact etiology is yet to be
      revealed. Most cases resolve spontaneously without the need for medical or
      surgical intervention, but more severe cases may result in devastating visual and
      cosmetic results. In recent years, there has been a significant progress in the
      understanding of the disease and the medical and surgical treatment of T.O. This
      work reviews new aspects of T.O and it's surgical treatment, and include clinical
      photographs of patients operated on in our department.

PMID- 12803065
TI  - [Witches saints and other diseases].
AB  - Salem, was the site at which Massachusetts was established in 1632, however, it
      is more famous for the witch-hunt that took place there 60 years later by some
      riotous puritans. Several teenaged girls that were struck by delirious fits and
      seizures captured the center of the stage. The local physicians, who could not
      come up with a medical solution, explained the strange phenomenon as witchcraft.
      The new world's moral code was brought to trial along with 20 innocent men who
      were accused, convicted and executed for the crime of practicing witchcraft. In
      this article we will try to acquit these men by introducing historical, medical
      and circumstantial evidence that ergot and alkaloids substances, produced by a
      mold called Claviceps purpura, may have been responsible for an intoxication that
      could account for the events of Salem 1692. Furthermore, we will try to explain
      how this ergot intoxication, also referred to as Saint Anthony's fire, has had a
      crucial influence on modern history including the Black Death plague that struck
      Europe since the 14th century.

PMID- 12803066
TI  - The genesis of flash photolysis.
AB  - A brief account is given of the construction of the first flash photolysis
      apparatuses at Cambridge and their application to gas phase systems.

PMID- 12803067
TI  - Flash photolysis and triplet states and free radicals in solution.
AB  - A personal account is given of the development of microsecond flash photolysis in
      George Porter's laboratory at Cambridge in the early 1950s. This made possible,
      for the first time, the observation of the absorption spectra of the lowest
      triplet states of many polycyclic aromatic hydrocarbons in fluid solutions. The T
      T transitions were found to be very intense with oscillator strengths approaching
      unity in many cases. Detailed kinetic studies showed that triplet state decay was
      first order and viscosity dependent and strongly quenched by dissolved oxygen.
      Several aromatic free radicals such as benzyl were also observed in liquid
      solution for the first time. The advent of the laser in the early 1960s made it
      possible to extend flash photolysis studies to the ns and ps and eventually the
      fs time range. Such studies have revolutionized the study of excited states and
      free radicals and have made possible advances in the understanding of the
      dynamics of chemical and biological systems that would have been unimaginable 60
      years ago.

PMID- 12803068
TI  - Photochemical molecular devices.
AB  - The concept of a macroscopic device can be extended to the molecular level by
      designing and synthesising (supra)-molecular species capable of performing
      specific functions. Molecular devices operate via electronic and/or nuclear
      rearrangements and, like macroscopic devices, need energy to operate and signals
      to communicate with the operator. The energy needed to make a device work can be
      supplied as chemical energy, electrical energy, or light. Luminescence is one of
      the most useful techniques to monitor the operation of molecular-level devices.
      The extension of the concept of a device to the molecular level is of interest,
      not only for basic research, but also for the growth of nanoscience and the
      development of nanotechnology. Molecular-level devices should find applications
      in information storage, display, and processing; in the long run, they are
      expected to lead to the construction of molecular-based (chemical) computers. In
      this perspective article, some of the most recent achievements in the field of
      photochemical molecular devices will be illustrated, with particular reference to
      (i) devices for photoinduced energy or electron transfer; (ii) devices for
      information processing based on photochemical or photophysical processes; (iii)
      devices designed to obtain extensive conformational changes upon photoexcitation
      (photochemically driven molecular machines).

PMID- 12803069
TI  - Ruthenium(II)-tris-bipyridine/titanium dioxide codoped zeolite Y photocatalysts:
      II. Photocatalyzed degradation of the model pollutant 2,4-xylidine, evidence for
      percolation behavior.
AB  - A considerably arduous test of a novel class of composite materials consisting of
      [Ru(bpy)3]2+ and TiO2 codoped zeolites Y is presented here. The [Ru(bpy)3]2+ and
      TiO2 codoped zeolites Y served as photocatalysts in the oxidation of the model
      compounds 2,4-dimethylaniline (2,4-xylidine) by H2O2 in an acidic aqueous medium.
      Zeolite-embedded TiO2 (nano)particles play an important role in the degradation
      mechanism. The first step in this complex mechanism is the photoelectron transfer
      from photoexcited [Ru(bpy)3]2+*, located inside the supercage of zeolite Y, to a
      neighboring TiO2 nanoparticle. During this electron transfer process, electron
      injection into the conduction band of TiO2 is achieved. The second decisive step
      is the reaction of this electron with H2O2, which was previously chemisorbed at
      the surface-region of the TiO2 nanoparticles. In this reaction, a TiO2 bound
      hydroxyl radical (TiO2-HO.) is created. This highly reactive intermediate
      initiates then the oxidation of 2,4-xylidine, which enters the zeolites framework
      in its protonated form (Hxyl+). The formation of 2,4-dimethylphenol as first
      detectable reaction product indicated that this oxidation proceeds via an
      electron transfer mechanism. Furthermore, [Ru(bpy)3]3+, which was created in the
      initiating photoelectron transfer reaction between [Ru(bpy)3]2+* and TiO2, also
      takes place in the oxidation of Hxyl+. [Ru(bpy)3]2+ is recycled in that reaction,
      which also belongs to the group of electron transfer reactions. In addition to
      the primary steps of this particular Advanced Oxidation Process (AOP), the
      dependence of the efficiency of the 2,4-xylidine degradation as a function of the
      [Ru(bpy)3]2+ and TiO2 loadings of the zeolite Y framework is also reported here.
      The quenching of [Ru(bpy)3]2+* by H2O2 as well as the photocatalytic activity of
      the [Ru(bpy)3]2+ and TiO2 codoped zeolite Y catalysts both follow a distinct
      percolation behavior in dependence of their TiO2 content.

PMID- 12803070
TI  - TiO2-promoted mineralization of organic sunscreens in water suspension and sodium
      dodecyl sulfate micelles.
AB  - The photostability of the widely used UVB sunscreen agents 2'-ethylhexyl-2-cyano
      3-phenylcinnamate (1), 2-hydroxy-4-methoxybenzophenone (2), octyl salicilate (3),
      and 2'-ethylhexyl-4-methoxycinnamate (4) has been investigated under UVA
      irradiation in the absence and presence of TiO2, an inorganic filter commonly
      employed in combination with organic filters in sunscreen preparations. In the
      absence of TiO2, 1-3 are photostable and 4 undergoes the expected E-Z
      isomerization; the presence of TiO2 caused mineralization of the organic filters
      and, surprisingly, the process is noticeably faster in the presence of surfactant
      than in sunscreen and water suspensions. The results indicate that in water
      suspension, mineralization is likely to occur on or near the TiO2 particle
      surface; when the organic sunscreens are segregated in the micelle core, reactive
      radicals, produced during TiO2-promoted degradation of the micellar system, may
      participate in sunscreen degradation. In addition, a pre-fluorescent probe for
      carbon-centered radical detection, 4-(3-hydroxy-2-methyl-4-quinolineoxy)-2,2,6,6
      tetramethylpiperidine-1-oxyl free radical or QT (5), was employed to demonstrate
      that carbon-centered radicals are evolved during micelle degradation and may
      participate in the mineralization of sunscreens.

PMID- 12803071
TI  - Ultrafast charge separation and radiationless relaxation processes from higher
      excited electronic states of directly linked porphyrin-acceptor dyads.
AB  - We have investigated photoinduced electron transfer (ET) and related processes
      from the higher excited electronic state (S2) of Zn-porphyrin-imide acceptor
      directly linked supramolecular systems (ZP-I) designed especially for the
      critical studies of the energy gap law (EGL) of the charge separation (CS) from
      the S2 state, effects of solvent dynamics and intramolecular vibrations on this
      CS, and competition or cooperation between this CS and S2-->S1 conversion, etc.
      In this study, we have confirmed the modification of the EGL for the CS from S2
      induced by the change of solvent polarity by comparing the EGL in toluene
      solution with that in THF, i.e. the EGL in toluene extends over a wider range of
      the energy gap for CS in the inverted region and becomes somewhat similar to the
      case of the weak coupling limit of an intramolecular radiationless transition.
      Moreover, we have compared the rate constants (lambda p) of the S1 state
      formation by the S2 excitation with the decay rate constants (lambda 1) of the S2
      state in the ZP-I series and have also examined solvent polarity effects on these
      rate constants comparing THF and toluene solutions. Our studies have revealed
      that S1 formation by S2 excitation occurs mainly due to the CS in S2 followed by
      charge recombination (CR) producing S1, and these processes are affected by the
      modification of EGL owing to the solvent polarity, resulting in the smaller
      lambda p in toluene.

PMID- 12803072
TI  - Direct proof of electron transfer in a rigid first generation triphenyl amine
      core dendrimer substituted with a peryleneimide acceptor.
AB  - The combination of nanosecond transient absorption experiments and single photon
      timing experiments proved the occurrence of an electron transfer process in the
      triphenyl amine core dendrimer, N1P1, by demonstrating the presence of an ion
      pair absorption for N1P1 in solvents of medium polarity. By means of femtosecond
      transient absorption measurements the rise time of this ion-pair absorption
      dominated by the radical anion absorption could be determined, resulting in a
      value of 180 ps in MeTHF and 138 ps in THF. Furthermore, in femtosecond
      fluorescence upconversion as well as in monochromatic femtosecond transient
      absorption, a few ps component was resolved which was assigned to a vibrational
      and solvent relaxation process of the locally excited singlet state of the
      peryleneimide.

PMID- 12803073
TI  - Time-dependent density functional theory treatment of the first UV absorption
      band in all-transoid permethyloligosilanes SinMe2n + 2 (n = 2-8, 10).
AB  - The TD B3LYP/6-311G(d,p) method slightly overestimates the excitation energies of
      the first UV absorption band of the all-transoid conformers of SinMe2n + 2 (n = 2
      8, 10), deduced from temperature-dependent measurements on conformer mixtures in
      hydrocarbon solvents, by a nearly constant amount (approximately 2000 cm-1). The
      TD B3LYP/6-31G(d) results are less satisfactory. The first band is calculated to
      be due to a sigma pi * excitation in Si2Me6 and to a superposition of overlapping
      sigma sigma * and sigma pi * excitations in the longer oligosilanes. The sigma pi
      * excitation is calculated to lie a little below the sigma sigma * excitation up
      to Si4Me10, the two transitions are nearly degenerate in Si5Me12, and the sigma
      sigma * excitation drops increasingly below the sigma pi * as the chain length is
      extended. The dipole strength of the sigma sigma * excitation grows by 4.8 D2 (D
      = debye) per added SiSi bond (more slowly up to n = 5) and the calculation
      overestimates it by a factor of about three. The sigma pi * excitation is
      computed to carry no or almost no oscillator strength, but as noted earlier by
      others, its presence is critical for the interpretation of the observed
      thermochromism. Upon cooling below room temperature, the first absorption maximum
      is blue-shifted in short chains and red-shifted in long chains. Unlike the prior
      investigators, we attribute the blue shift to the disappearance of hot bands
      built on the sigma pi * origin using intensity borrowing sigma-pi mixing
      vibrations (b1 in Si3Me8). As usual, the red shift is attributed to the
      disappearance of twisted conformers, which have higher calculated sigma sigma *
      excitation energies.

PMID- 12803074
TI  - Quantitative rate constants for the reaction of dyes and alkenes with alpha
      hydroxyalkyl radicals, measured by laser flash photolysis.
AB  - Rate constants are measured for the addition reactions of 1-hydroxy-1-cyclohexyl
      (1HC) and 2-hydroxy-2-propyl (2HP) radicals to 7 alkenes and for the 1-electron
      reduction of 16 organic dyes by 1HC, and a subset of 5 of these dyes by 2HP. This
      was done to determine to what extent the many reported rate constants for
      reactions of 2-hydroxy-2-propyl radicals (2HP) may be used to predict the rates
      of reactions of other tertiary alpha-hydroxy-alkyl radicals, and to give a better
      understanding of the factors that control dye reduction. The dyes were chosen to
      represent a wide range of dye types (azo, anthraquinone, phthalocyanine, triaryl
      methane, indocyanine and azine dyes). Radicals were produced by laser flash
      photolysis of the corresponding tertiary alpha-hydroxyketone giving carbonyl and
      tertiary alpha-hydroxy-alkyl radicals. Control experiments with a bis
      acylphosphine oxide were carried out which clearly demonstrated that the carbonyl
      radicals did not interfere with the kinetics. On average the addition and
      reduction rate constants for 1HC are only 20% lower than for 2HP. Larger
      decreases are observed for sterically congested alkenes due to the increased
      steric bulk of 1HC. The rate constants for 1-electron reduction of the dyes are
      in the range 4 x 10(7) to 6 x 10(9) mol-1 1 s-1 and may be predicted, reasonably
      well using the Marcus equation with a reorganisation energy, lambda = 182 kJ mol
      1.

PMID- 12803075
TI  - Primary photoreactions of phylloquinone (vitamin K1) and plastoquinone-1 in
      solution.
AB  - The photoreactions of electron transport quinones vitamin K1 (1) and
      plastoquinone-1 (2) were studied by picosecond pump-probe spectroscopy,
      nanosecond flash photolysis, step-scan FTIR spectroscopy, and by irradiation in
      glassy solvents at 77 K with optical and EPR detection. In polar solvents, charge
      transfer from the beta,gamma-double bond to the quinone moiety initiates
      intramolecular proton transfer from the side chain, k = 2.7 x 10(11) s-1,
      yielding 1,3-quinone methide diradicals, which establish a metastable equilibrium
      between the singlet and the triplet state. Subsequent proton transfer through the
      solvent forms 1,2-quinone methides. In apolar solvents the predominant primary
      photoreaction is formation of cyclic 'preoxetane' diradicals (kform > 3 x 10(11)
      s-1, kdecay approximately 1 x 10(9) s-1), which revert to a photostationary E/Z
      mixture of the starting materials, unless they are trapped by oxygen. The
      beta,gamma-double bond in the isoprenoid side chain thus provides two efficient
      deactivation processes, which prevent the intermolecular photoreactions commonly
      observed with the parent quinones. A combined mechanistic scheme rationalizes the
      known photoreactions of 1, 2 and related compounds in solution.

PMID- 12803076
TI  - Interaction of the allophycocyanin core complex with photosystem II.
AB  - Allophycocyanin core complexes were purified from the thermophilic cyanobacterium
      Thermosynechococcus elongatus and analysed by negative-stain electron microscopy
      and single-particle averaging. The purified complex was found to consist of three
      allophycocyanin cylinders. The single-particle analysis of end-on views of the
      complex revealed a mirror axis, indicative of two-fold symmetry. This observation
      allowed the assignment of the allophycocyanin base cylinders and the
      identification of their potential interaction sites with the thylakoid membrane
      and with the photosystem II reaction centre in particular. The T. elongatus
      allophycocyanin core projection map, together with published information on the
      structure of photosystem II for the same organism, was used to construct a model
      for the allophycocyanin core-photosystem II dimer supercomplex, from which
      docking sites between both complexes are suggested. The implications of this
      association for energy transfer from allophycocyanin to photosystem II are
      discussed.

PMID- 12803078
TI  - Spectroscopy of photoinduced charge-transfer reactions between tetrasulfonated
      aluminium phthalocyanine and methyl viologen.
AB  - Interactions between tetrasulfonated aluminium phthalocyanine (AlPcTS4-) and
      methyl viologen (Mv2+) have been studied in water and ethanol solutions using
      several experimental techniques. UV-visible absorption and fluorescence
      spectroscopies show that ion-pair complexes occur in ethanol, disappearing in
      more polar environments such as water. Time-resolved fluorescence spectroscopy
      (picosecond timescale) reveals the existence of several emissive species in
      ethanol solutions, of which one of the components is attributed to the charge
      transfer complex (AlPcTS4-)(Mv2+)2, another to higher-order aggregates and yet
      another to the isolated AlPcTS4- molecule. The AlPcTS4- emission is quenched by
      Mv2+, leading to transient diffusion in the fluorescence decay kinetics. On the
      other hand, the emissive complex has an exponential decay with a relatively long
      lifetime (above 1 ns). Time-resolved absorption measurements did not reveal the
      existence of radicals in aqueous solution, even on the picosecond timescale. The
      spectra reveal the presence of excited singlet state AlPcTS4-, which decays via
      the triplet excited state back to the ground state.

PMID- 12803077
TI  - The photophysics of fac-[Re(CO)3(dppz)(py)]+ in CH3CN: a comparative picosecond
      flash photolysis, transient infrared, transient resonance Raman and density
      functional theoretical study.
AB  - The photophysical properties of fac-[Re(CO)3(dppz)(py)]+ (1, where dppz =
      dipyrido[3,2-a: 2',3'-c]phenazine) in CH3CN have been investigated using a series
      of complementary techniques including visible and infrared transient absorption
      and resonance Raman spectroscopy on the picosecond and nanosecond timescales. The
      results confirm previous reports that the lowest-lying emissive state in 1 is a
      triplet intra-ligand (3IL) state localised on the dppz ligand and have provided
      detailed information on the dynamics of 1 upon photoexcitation, including the
      relative energies of the excited state species encountered and the electronic
      distribution within these. If the dppz ligand is viewed in terms of
      phenanthroline (phen) and phenazine (phz) moieties, the emissive state is
      probably more accurately described as a 3 pi-->pi *(phz) IL state. The picosecond
      studies have shown that this emissive state is formed, at least in part, within
      30 ps of excitation from a precursor, which is possibly a 3 pi-->pi *(phen) IL
      state. On the nanosecond timescale, TRIR has been employed to elucidate further
      dynamics and reveal the presence of an energetically close-lying state in
      equilibrium with the emissive state. This has tentatively been assigned as being
      3d pi(Re)-->pi *(phz) metal-to-ligand charge transfer (MLCT) in nature. A summary
      of the photophysics is proposed in the form of a Jablonski scheme. Time dependent
      density functional theory (TD-DFT) calculations support the relative ordering and
      suggested electronic character of the excited state species involved.

PMID- 12803079
TI  - Triplet energies and the singlet oxygen quenching mechanism for 7H-pyrazolo[5,1
      c]-1,2,4-triazole azomethine dyes.
AB  - Analysis of triplet energy transfer rate constants gives the triplet energies of
      six 7H-pyrazolo[5,1-c]-1,2,4-triazole azomethine dyes, with lambda max values in
      the range 546-633 nm in ethanol, to lie in the range 115-88 kJ mol-1. Energy
      transfer rates from porphyrin and phthalocyanine sensitisers can be well
      approximated using the Balzani equation with a zero or small reorganization
      energy, and a transmission coefficient ca. 1/1000 that of the fully adiabatic
      value. A comparison of data on triplet energies of azomethine dyes suggests a
      relationship between the dye absorption energies and triplet energies of the
      form: ET = 0.69(+/- 0.04)(E lambda max)-33(+/- 9) kJ mol-1. A detailed study of
      the quenching of 1O2* by one of the dyes shows that this reaction is accompanied
      by isomerisation of the dye. This is interpreted as strong indirect evidence for
      an energy transfer mechanism for the process, a conclusion which is supported in
      a general way by the value of the 1O2* quenching rate constant.

PMID- 12803080
TI  - Deactivation processes of the lowest excited state of [UO2(H2O)5]2+ in aqueous
      solution.
AB  - A detailed analysis of the photophysical behaviour of uranyl ion in aqueous
      solutions at room temperature is given using literature data, together with
      results of new experimental and theoretical studies to see whether the decay
      mechanism of the lowest excited state involves physical deactivation by energy
      transfer or a chemical process through hydrogen atom abstraction. Comparison of
      the radiative lifetimes determined from quantum yield and lifetime data with that
      obtained from the Einstein relationship strongly suggests that the emitting state
      is identical to that observed in the lowest energy absorption band. From study of
      the experimental rate and that calculated theoretically, from deuterium isotope
      effects and the activation energy for decay support is given to a deactivation
      mechanism of hydrogen abstraction involving water clusters to give uranium(v) and
      hydroxyl radicals. Support for hydroxyl radical formation comes from electron
      spin resonance spectra observed in the presence of the spin traps 5,5-dimethyl-1
      pyrroline N-oxide and tert-butyl-N-phenylnitrone and from literature results on
      photoinduced uranyl oxygen exchange and photoconductivity. It has previously been
      suggested that the uranyl emission above pH 1.5 may involve an exciplex between
      excited uranyl ion and uranium(v). Evidence against this mechanism is given on
      the basis of quenching of uranyl luminescence by uranium(v), together with other
      kinetic reasoning. No overall photochemical reaction is observed on excitation of
      aqueous uranyl solutions, and it is suggested that this is mainly due to
      reoxidation of UO2+ by hydroxyl radicals in a radical pair. An alternative
      process involving oxidation by molecular oxygen is analysed experimentally and
      theoretically, and is suggested to be too slow to be a major reoxidation pathway.

PMID- 12803081
TI  - Ultrashort-lived excited states of aminophthalimides in fluid solution.
AB  - The Sn-->S0 ultraviolet fluorescence spectra (270-380 nm) of 4-aminophthalimide
      (4AP) and its N-methyl derivative 4-amino-N-methylphthalimide (4ANMP) are
      reported, following the absorption of two laser pulses. In polar but non-hydrogen
      bonding solvents, both molecules exhibit a principal emission maximum near 290
      nm, whereas solutions in hydrogen-bonding solvents display two prominent emission
      bands, near 300 and 350 nm. The relative intensities of these bands depend on
      solvent type and, in a pump-probe experiment, on the wavelengths and temporal
      spacing of two ultrashort pulses. Experiments covering the range approximately
      0.1-100 ps showed evidence for at least two distinct ultrashort relaxation
      processes, the rates of which depend on solvent. Fluorescence upconversion
      experiments at < 0.2 ps resolution have shown that the longer-duration process
      correlates with the fluorescence Stokes shift, and provide evidence that the
      solvent-dependent shift of the S1-->S0 fluorescence spectrum is reflected in the
      fluorescence quantum efficiency of a nearby electronic state.

PMID- 12803082
TI  - Excited state dynamics and rapid internal conversion in a stable dipole molecule.
AB  - The excited singlet state of an azomethine ylide or 'stable dipole' exhibits an
      ultrafast radiationless relaxation after femtosecond laser excitation. These
      transients are observed before the excited state decays in an almost
      activationless manner, the barrier is 440 cm-1, to the ground state with a 1.5 ps
      lifetime. Cooling of the hot ground state is also apparent in the transient
      absorption data and in methanol decays with a 5.7 ps lifetime. The viscosity
      dependence of the fluorescence yield and lifetime in different solvents is small
      and far less pronounced than in triphenylmethane dyes. Surprisingly, the excited
      state decay is not due to twisting about the C-N bond of the ylide but it is
      caused by buckling of one of the rings as the nitrogen atom changes character
      from sp2 to sp3 hybridisation.

PMID- 12803083
TI  - Preparation and characterisation of novel thick sol-gel titania film
      photocatalysts.
AB  - The preparation and characterization of thick (9 microns), clear, mechanically
      robust and photocatalytically active films of nanocrystalline anatase titania are
      described. XRD and SEM analysis show the films comprise 13 nm particles of
      anatase TiO2. Thin (54 nm) films of the 'paste' TiO2, along with sol-gel titania
      films made by a more traditional route are also prepared and characterised. All
      titania films mediate the photocatalytic destruction of stearic acid with a
      quantum yield of 0.0016 +/- 0.0003, using either 365 nm (i.e. BLB) or 254 nm
      (germicidal) light. P25 TiO2 films also appear to mediate the same process with a
      similar formal quantum efficiency. Of all the films tested, the thick paste TiO2
      films are the most ideally suited for use with near UV light, for reasons which
      are discussed. All the titania films tested exhibit photoinduced
      superhydrophilicity.

PMID- 12803084
TI  - Non-covalent dendrimer-porphyrin interactions: the intermediacy of H-aggregates?
AB  - The interaction of anionic meso-tetrakis(4-sulfonatophenyl)porphyrin (TSPP) with
      poly(amidoamine) (PAMAM) dendrimers of generations 2 and 4 in aqueous solution
      was investigated with steady-state absorption and fluorescence techniques. At low
      dendrimer concentrations, the formation of low absorptive/emissive species occurs
      in these systems. With an increase of dendrimer concentration, the porphyrins
      rearrange at the dendritic outer shell and the absorption and emission spectra
      suggest the presence of H-aggregates of TSPP. These aggregates dissociate to
      yield monomeric complexed species in the limit of high dendrimer concentration,
      which presents very similar spectra for both generations studied. On the other
      hand, the emission of the same systems at pH 2 shows significant differences
      between dendrimer generations. While for generation 2 the fluorescence spectra
      practically coincide with that of the diacid TSPP and its J-aggregate, for
      generation 4 the spectra obtained are similar to that at high pH. This was
      interpreted according to a morphologic transition in PAMAM dendrimers around
      generation 3, to give a more compact structure, which provides a hydrophobic
      environment for the associated TSPP. At low pH, an increase in J-aggregation is
      observed in the dendrimer's presence. Aging effects were observed, in particular
      for the systems where different aggregated forms of TSPP coexist, showing that
      for intermediate dendrimer concentrations these are thermodynamically labile
      systems.

PMID- 12803085
TI  - Fluorescence quenching of Acridine Orange in microemulsions induced by the non
      steroidal anti-inflammatory drug Piroxicam.
AB  - The singlet excited-state quenching of Acridine Orange (AO) by methyl viologen
      (MV2+) and the non-steroidal anti-inflammatory drug Piroxicam (Prx), incorporated
      in sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/isooctane/water and Triton X-100
      (Trx-100)/cyclohexane-hexanol/water (w/o) microemulsions, was followed by steady-
      and transient-state fluorescence. The water content was varied by using different
      values of omega 0 (omega 0 = [H2O]/[S]) at fixed AOT (0.1 M) and Trx-100 (0.2 M)
      concentrations. In AOT, MV2+ resides at the interface, while Prx partitions
      between the interface and bulk water, but considerably biased towards the latter
      compared to AO. The quenching process efficiency increases with increasing omega
      0, but reaches a diffusional value similar to that of free water only for the
      case of Prx, underlining the electrostatic effect of the AOT interface. The
      quenching process in Trx-100 microemulsions is more efficient for Prx than for
      MV2+, pointing to a similar polyoxyethylene intra-chain location for the former
      and AO. In both cases, data obtained allowed the microviscosity of the aqueous
      interior at different omega 0 to be extrapolated and indicate an increase in eta
      w values with water content, reflecting changes in the shape of Trx-100
      microemulsions, which occur at omega 0 = 8.

PMID- 12803086
TI  - The fluorescence and photostabilities of naturally occurring isoflavones.
AB  - The 5,7-dihydroxyisoflavones do not emit detectable fluorescence and are
      significantly more photostable than the two 7-hydroxy-5-deoxyisoflavones,
      daidzein and formononetin. The latter isoflavones emit fluorescence that depends
      on the basicity of the solution and the polarity of the solvent. Comparison of
      the spectral distributions of the emission in methanol in the presence and
      absence of base indicates that it originates from the conjugate anion excited
      singlet states. The fluorescence of daidzein and formononetin exhibit large
      Stokes shifts to longer wavelengths in methanol, ethanol, hexanol and
      acetonitrile and the magnitudes of these shifts increase with solvent polarity.
      This indicates that the emission originates from excited singlet states with much
      larger dipole moments than those of the corresponding ground states. Values of
      8.3 D and 6.5 D were determined for daidzein and formononetin respectively. The
      photostabilities of formononetin and daidzein both increase with increasing
      solvent polarity and in corresponding solvents, the photostability of daidzein is
      higher than that of formononetin, behaviour which is attributed to the greater
      antioxidant activity of daidzein.

PMID- 12803087
TI  - Calculation of triplet-triplet energy transfer rates from emission and absorption
      spectra. The quenching of hemicarcerated triplet biacetyl by aromatic
      hydrocarbons.
AB  - The kinetics of triplet-triplet (T-T) energy transfer have been analysed with a
      view to linking theories of chemical reactions (involving the rupture and
      formation of bonds) with theories of processes, such as electron transfer or
      energy transfer, which preserve chemical bonding. As for the latter, our analysis
      does not support the claim that, of the two rival expressions for T-T energy
      transfer, both rooted in the golden rule, only one is applicable to electron
      transfer or T-T transfer. Though the two expressions do reflect different
      standpoints, the distinction is eroded by the assumption of a delta-function
      distribution for the vibrational spectrum. It is shown that theories of chemical
      reactions also furnish estimates of Franck-Condon factors; rates of chemical
      reactions and chemical processes are both related to the properties (strengths
      and lengths) of the reactive bonds, but differ in the mode of energy dissipation.
      The relationship between the rates of reactions and processes presents new
      possibilities for a unified view of chemical reactivity.

PMID- 12803088
TI  - [Nurse management of cancer patients?].

PMID- 12803089
TI  - [The role of paclitaxel in the first line treatment of cancer of the ovary?].

PMID- 12803090
TI  - From forensics to dementia: proposed nursing education legislation.

PMID- 12803091
TI  - Funding reductions threaten to lock out nursing students.

PMID- 12803092
TI  - Update: smallpox vaccination program.

PMID- 12803093
TI  - Workplace safety update: latex allergy.

PMID- 12803094
TI  - What can we do to reduce the rate of medical errors?

PMID- 12803095
TI  - Smoking, quitting, and relapse in surgical patients: a simple, clinic-based
      assessment and intervention that works.
AB  - This paper presents an overview of the current clinical practice guidelines for
      tobacco dependency and application in surgical patients in clinic settings. The
      paper covers the nursing care including assessment of tobacco dependency,
      verification of smoking status, easy-to-use paper and pencil tests and
      instruments, assessing stage of change, and developing a plan. Discussion also
      provides ways to help with relapse and sustaining long-term change.

PMID- 12803096
TI  - Self-esteem and cosmetic surgery: is there a relationship between the two?
AB  - This article addresses the correlation between a patient's self-esteem and the
      demand for and use of cosmetic surgery. The greater purpose of this article is to
      broaden nurses' understanding of the profound influence of self-esteem as it
      relates to cosmetic surgery patients and their decision to have surgery.

PMID- 12803097
TI  - Report to the PSNCB directors: examination administrations from October 2001
      through April 2002.

PMID- 12803098
TI  - Microwave ovens in the OR.

PMID- 12803099
TI  - No profession is without risk: what one state is doing ... Kentucky.

PMID- 12803100
TI  - Mixing medicines, herbs, food, and surgery.

PMID- 12803102
TI  - New software tool links quality with lower costs.

PMID- 12803101
TI  - Are you monitoring these critical performance metrics?

PMID- 12803104
TI  - California IPA coasting on these rates, but still tweaking model.

PMID- 12803103
TI  - AHA data offer insights into hospital cost, utilization trends.

PMID- 12803105
TI  - Thrombophilia: hereditary and acquired in cardiovascular disease.

PMID- 12803106
TI  - Differences in significance of drug resistance mechanisms between adult and
      childhood acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is now curable in 60-80% of children. In
      adults, in spite of adopting treatment protocols based on therapy for childhood
      ALL, the disease is still curable in 30-40% of patients only. These worse results
      of therapy may be due to the induction of various cell defence mechanisms, such
      as activation of P-glycoprotein, which protects man against xenobiotics. Among a
      number of various multi-drug resistance mechanisms, differences between adults
      and children with ALL have been found only for higher P-glycoprotein expression
      and possibly more often p53 gene mutations in adults. Induction of expression of
      drug resistance proteins during chemotherapy and co-existence of various
      mechanisms are common phenomena in adult ALL. Differences in resistance to
      different drugs might contribute to the impact of age on the outcome of ALL. The
      underlying mechanisms for these differences are still largely unknown; however,
      knowledge about drug resistance mechanisms can lead to new therapeutic options.

PMID- 12803107
TI  - Effect of tresperimus on ex vivo expansion of CD34+CD38(-)-enriched cord blood
      cells.
AB  - Tresperimus, an analogue of 15-deoxyspergualine (15-DSG), has been found, in
      rodents, to induce a potent state of tolerance after organ and bone marrow
      allografts. In a previous study, we have reported that tresperimus at the optimal
      concentration of 0.5 microgram/ml supports the clonogenic potential of human cord
      blood CD34+ cells. Dose dependent inhibition of clonogenesis was also observed
      with complete reversibility following drug withdrawal. In this study, we tested
      the effect of 0.5 microgram tresperimus/ml on ex vivo expansion of primitive
      human cord blood CD34+CD38- cells. Our findings revealed that the total number of
      expanded cells was decreased in the presence of tresperimus. However, the
      multipotential and erythroid colonies were significantly increased in the
      presence of tresperimus compared with control cultures done without the test
      drug. Progenitor cell morphology was comparable in both test and control
      cultures. The telomerase activity was consistently lower in tresperimus-treated
      hematopoietic progenitors than in control cultures. These results suggest that
      tresperimus preserves primitive CD34+CD38- cells in a state of high potentiality
      while limiting the total number of their differentiated progeny. Bearing in mind
      that the test drug supports the clonogenic potential of CD34+ cells, the overall
      findings emphasize the importance of assessing the effect of tresperimus on in
      vivo long-term hematopoiesis which could predict the potential clinical use of
      tresperimus in the prevention of graft-versus-host disease in recipients of
      allogeneic bone marrow.

PMID- 12803108
TI  - Plasticity: advantages over cloning and gene therapy.

PMID- 12803109
TI  - The role of L-carnitine on a restricted number of myeloid leukemia progenitor
      cells: generation of atypical cell types.
AB  - AIM: Since cellular maturation largely depends on lipid metabolism, we examined
      whether L-carnitine (L-C), a substance involved in these biochemical pathways, is
      able to promote differentiation of the promyelocytic cell line HL-60. METHODS:
      Differentiation was assessed by marker analysis, morphology,
      immunohistochemistry, proliferation and cellular activity assays. RESULTS: L-C
      increases HLA-DR and CD14 surface antigens, while morphologic and marker analysis
      of the treated cells reveals the presence of monocytes, neutrophiles and few
      dendritic cells. What is important, however, is the induction of cells that have
      an atypical to this pathway allure staining positive for the neurofilament 3A10
      monoclonal antibody, specific for nerve cells and the anti-p75 (Nerve Growth
      Factor Receptor) monoclonal antibody. The events described concern active and, at
      the same time, not proliferative senescent cells. CONCLUSIONS: L-C exerts its
      differentiation action on a certain fraction of the leukemic population yielding
      a non-negligible number of atypical for the myeloid lineage cells. These findings
      complement earlier and recent reports that describe the generation of cells of a
      different lineage irrelevant to their parent line of differentiation indicating
      that the hemopoietic pool appears to be the source of any kind of cell types
      according to the stimulus provided. Thus, in the context of the plasticity theory
      it appears that the HL-60 cell line also possess the potential to differentiate
      towards unexpected pathways.

PMID- 12803110
TI  - Experience with predeposition of autologous blood in elective orthopaedic and
      plastic surgery: the role of oral iron medication.
AB  - The risk of transmission of transfusion-associated infections, mainly AIDS, led
      to the increased use of autologous transfusion by four methods: predeposition of
      autologous blood, haemodilution, intraoperative and postoperative blood salvage.
      We started a program of autologous predeposition at blood transfusion centre of
      Saint Andrews General Hospital of Patras in co-operation with orthopaedic and
      plastic surgery in 1992. To date, 617 autologous units have been collected from
      257 patients undergoing various operations. Our protocol was as follows: the
      minimum Hb value before each donation was 12 g/dl, body weight over 50 kg, age 18
      70 years and 8-10 day intervals between donations. The exclusion criteria were
      anaemia, evidence of blood loss, renal disease, chronic and acute inflammatory or
      malignant disorders, pregnancy and lactation. We chose 40 patients with
      haemoglobin values of 13-15 g/dl and ferritin levels > 50 ng/ml, who gave three
      autologous units. They were separated in two groups of twenty patients. Those in
      group 1 received 300 mg of elemental iron in three daily oral doses, while the
      others in group 2 received no iron medication. We studied haematologic variables,
      reticulocytes and ferritin levels in both groups before each autologous donation.
      We also studied the possible complications and their incidence in patients over
      60 years old. According to our results, haematologic variables such as Hb, mean
      corpuscular Hb (MCH), mean corpuscular volume (MCV) and reticulocytes were not
      influenced by oral iron therapy. We observed a slight increase in MCV in both
      study groups which means the production of larger red blood cells. We also
      noticed a higher decrease of ferritin in patients with no iron therapy, but
      without a fall of ferritin levels under the normal values. We conclude that oral
      iron therapy in non-iron deficient patients undergoing a moderate program of
      three autologous units is not necessary. In addition, autologous blood donation
      is also feasible in patients over 60 years old without severe complications.

PMID- 12803111
TI  - Quantitative, functional, morphological and ultrastructural recovery of platelets
      as predictor for cryopreservation.
AB  - Cryopreservation of platelets is of great interest, since it could extend the
      shelf life of therapeutic platelet concentrates and facilitate stockpiling and
      inventory control in blood banking. Despite the use of many cryopreservation
      procedures the optimal cryopreservation procedure is not defined yet. We have
      compared the cryopreservation of human platelets by various protocols employing
      controlled-rate and non-controlled-rate freezing procedures in combination with
      different concentrations of DMSO (6% and 10%) or 5% DMSO + 6% HES combination.
      After storage for 1 to 3 months, samples were thawed and analyzed. Measurements
      included cell recovery, platelet viability according to hypotonic shock response
      (HSR), platelet aggregation with ADP, morphological and ultrastructural
      properties of defrozen platelets. Our findings show that the application of our
      original procedure for controlled-rate freezing consisting of six cooling steps
      (cooling rate 1 degree C/min) with compensation of released heat of fusion
      (cooling rate 2 degrees C/min) has significantly influenced the quality of thawed
      platelets. At the same time, a concentration of 6% DMSO proved to be the most
      effective. In summary, cryopreservation of human platelets using controlled-rate
      freezing procedure in combination with lower (6%) DMSO concentration resulted in
      less damage from freezing and higher recovered function of platelets.

PMID- 12803112
TI  - High pretreatment interleukin-10 is an independent predictor of poor failure-free
      survival in patients with Hodgkin's lymphoma.
AB  - AIM: The aim of this study was to investigate the relationship of pretreatment
      serum IL-10 (sIL-10) levels with known prognostic factors and with failure-free
      survival (FFS) in patients with Hodgkin's lymphoma (HL). PATIENTS AND METHODS:
      Interleukin-10 (IL-10) levels were measured in the sera of 36 untreated patients
      with HL and were subsequently correlated with clinical and laboratory prognostic
      parameters as well as with FFS. RESULTS: 36 untreated HL patients (21 men, median
      age 31 (18-62) years) were studied. Of the subjects, 19 (52.7%) had elevated IL
      10 levels (> or = 10 pg/ml). High IL-10 correlated with bulky disease, high serum
      lactate dehydrogenase (LDH) and leukocytosis (P = 0.015 for all three variables).
      High IL-10 (P = 0.015) and low serum albumin (P = 0.001) were associated with
      worse FFS, but only high IL-10 emerged as an independent predictor of inferior
      FFS in multivariate analysis (P = 0.04, hazard ratio 2.21, 95% CI 1.12-14.67).
      Median FFS of IL-10-positive patients (30 (12-47) months) was significantly
      shorter compared to that of IL-10-negative ones (39 (12-58) months, log-rank test
      P = 0.0185). CONCLUSIONS: IL-10 was found to be elevated in approximately half of
      untreated patients with HL, to correlate with bulky disease, high LDH and
      leukocytosis and to be an independent predictor of FFS.

PMID- 12803113
TI  - The effect of leptin on engraftment in patients undergoing peripheral blood stem
      cell transplantation.
AB  - AIM AND BACKGROUND: To evaluate the alterations of serum leptin levels during
      stem cell transplantation and its possible role in engraftment. Thirty-two
      patients (19 male, 13 female) with various hematological and solid tumors and 28
      healthy subjects (15 male, 13 female) as a control group were enrolled in the
      study. METHODS: Serum leptin levels were measured on the day before administering
      G-CSF, at the time of leukapheresis harvest, on day +1st and +7th after
      transplantation and on the day of leukocyte engraftment. RESULTS: There was no
      significant difference in serum leptin levels between patients (mean +/- SEM,
      11.62 +/- 2.75 ng/ml) before transplantation and control groups (9.79 +/- 1.73
      ng/ml). Pre-G-CSF (baseline) level of serum leptin (11.62 +/- 2.75 ng/ml) was
      significantly decreased to 7.73 +/- 2.02 ng/ml at the time of apheresis harvest
      (P = 0.0029). Later, serum leptin levels increased to 16.75 +/- 3.26 ng/ml on day
      +1 after transplantation (P < 0.0001). Subsequently serum leptin levels both on
      day +7th posttransplant (12.11 +/- 2.17 ng/ml) and leukocyte engraftment day
      (9.26 +/- 1.50 ng/ml) were gradually decreased. There was no correlation between
      the serum leptin levels and the leukocyte or platelet engraftment. CONCLUSION:
      The present study concludes that serum leptin level does not change remarkably
      during peripheral blood stem cell transplantation and no association exists
      between circulating leptin levels and the onset of engraftment suggesting that
      circulating serum leptin does not have a significant direct influence on
      engraftment.

PMID- 12803114
TI  - Total skin electron beam therapy for cutaneous T-cell lymphoma: Turkish
      experience with translational technique.
AB  - Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. In our
      department, between January 1995 to January 2001, we treated eleven patients with
      mycosis fungoides by total body skin electron irradiation to evaluate its
      influence. According to our knowledge, our department is the only center in
      Turkey capable of applying total skin electron beam therapy. Total skin electron
      beam therapy was applied by using the "translational technique". Daily doses (4
      Gray) were given in a total of seven fractions according to the conventional
      fractionation scheme. There were 6 patients with stage I disease, 3 patients with
      stage II and 2 patients with stage IV disease. Except stage IV patients, we
      obtained good cutaneous results. According to our observation, in early stage
      mycosis fungoides total body skin electron irradiation can provide good cutaneous
      response, but for stage IV only moderate pallation can be obtained.

PMID- 12803115
TI  - Nutrition and acute leukemia in adults: relation to remission rate and survival.
AB  - Because malnutrition may augment myelotoxicity of antileukemic drugs, we tested
      whether changes of the nutritional state during first remission induction
      chemotherapy were related to remission rates and times. Thirty-seven adult
      patients, average 49 years (range 15-74), with acute leukemia were studied during
      first remission induction chemotherapy. Weight changes were classified into one
      of four separate groups, ranging from minimal weight changes to > 10 kg loss. The
      patients were followed until death or complete remission. During the induction
      period, patients lost (in mean) 5.1 kg body weight, had severe neutropenia (i.e.,
      less than 0.1 x 10(9)/1) and fever for 25-26% of this time. Patients exhibiting
      moderate weight reduction (i.e., 2-5.9 and 6-9.9 kg; n = 22) were neutropenic and
      febrile for 23% of the induction period; they displayed the highest remission
      rates, 90 and 92%, respectively. In contrast, patients in the minimal or maximal
      weight change groups (i.e. a loss of < 2 kg; n = 8, or > 10 kg; n = 7), showing
      shortest or longest duration of neutropenia (20% and 36%, respectively) and fever
      (25% and 42%), had the lowest remission rates, 50 and 63%, respectively. By
      logistic regression analyses, change of weight and time with fever were
      associated with remission rates. However, none of these variables were related to
      remission times. We may conclude that in adult acute leukemia patients a moderate
      weight loss (together with intermediate duration of neutropenia and fever) was
      associated with the highest remission rates.

PMID- 12803116
TI  - Bone marrow involvement in sarcoidosis: an analysis of 50 bone marrow samples.
AB  - The incidence of bone marrow involvement in sarcoidosis patients and changes in
      their peripheral blood parameters have been investigated. Out of 92 patients
      diagnosed with sarcoidosis at our center between 1994 and 2002, 50 (54.3%) gave
      consent for a bone marrow biopsy and were included into our study. The clinical
      features, peripheral blood parameters and bone marrow biopsy findings of the
      patients were analysed. Of these 50 patients, 39 were females and 11 were males
      (median age 37 years, range 16-62). Anemia was detected in 11 (22%) cases, and
      both anemia and leucopenia in 3 (6%). In 10% (5 patients; 3 males, 2 females) of
      the patients, bone marrow biopsy revealed noncaseatified granulomas. Sarcoidosis
      patients with bone marrow involvement had higher incidences of extrapulmonary
      involvement, leucopenia-lymphopenia and anemia than those without involvement (P
      values were 0.05, 0.001 and 0.06, respectively). Of the 11 patients with anemia,
      3 had involvement of the bone marrow by sarcoidosis and 7 had iron deficiency
      anemia. As a result, bone marrow involvement should be considered in sarcoidosis
      patients with anemia, leucopenia-lymphopenia, and also extrapulmonary
      involvement.

PMID- 12803117
TI  - Invasive pulmonary aspergillosis following bone marrow transplantation: risk
      factors and diagnostic aspect.
AB  - AIM: To describe the clinical features and diagnostic aspects of invasive
      pulmonary aspergillosis (IPA) following bone marrow transplantation (BMT).
      METHODS: Retrospective review of the medical records of all BMT recipients in
      whom Aspergillus spp. were isolated from the lower respiratory tract. The
      diagnosis of IPA was definite when the fungus was demonstrated by histological
      examination or culture of lung tissue obtained by biopsy or autopsy. The
      diagnosis was probable when Aspergillus spp. were isolated by culture of BAL or
      sputum, with compatible clinical and radiologic picture. RESULTS: There were 27
      patients with IPA post-BMT (81% allo versus 19% auto). The diagnosis was made
      median of 20-week posttransplanttation: 67% had GVHD, 59% were on
      immunosuppressive therapy and 89% were on corticosteroids. Only 11% had severe
      neutropenia (ANC < 500). The clinical symptoms were nonspecific, and
      radiologically the commonest manifestations were nodules with or without
      cavitation 34%. The diagnosis of IPA was definite in 11 patients (41%): 6 by open
      lung biopsy, 1 by CT-guided biopsy, 1 by BAL and brain biopsy and 3 by autopsy.
      The diagnosis was probable in 16 (59%): 6 by BAL, 7 by sputum culture and 3 both.
      Aspergillus spp. were recovered from 10/17 (59%) patients who had BAL and 10/15
      (67%) who had sputum culture. 25 patients were treated with antifungal agents (19
      amphtericin B alone, 4 amphotericin B and itraconacole, 2 variconazole). 16/27
      (59%) died a median of 15.5 days after the diagnosis of IPA. 5 had documented
      evidence of disseminated disease, most commonly to brain. CONCLUSION: IPA is an
      important problem following BMT. Allogeneric transplant, GVHD, immuno-suppressive
      and corticosteroid therapy are the main risk factors. BAL and sputum examination
      are helpful in making the diagnosis in the appropriate clinical setting. Although
      the mortality associated with IPA remains high, however it is lower than what was
      previously reported.

PMID- 12803118
TI  - Hematopoiesis during acute Toxoplasma gondii infection in mice.
AB  - We studied hematopoiesis in bone marrow and blood of CBA mice following infection
      with Toxoplasma gondii. Our data showed that acute infection with the virulent RH
      strain was associated with leucopenia, thrombocytopenia and bone marrow
      hypoplasia while, in spite of the infection-induced damage of the granulocyte
      cell lineage, in bone marrow stimulated production of granulocytes was revealed.
      In peripheral blood, T. gondii infection caused a significant decrease in the
      total number of white blood cells, reticulocytes and platelets. However, the
      relative proportion of granulocytes and lymphocytes was changed in favor of
      granulocytes, as compared to pre-infection levels. The functional activity of
      granulocytes was also increased. The bone marrow alterations were characterized
      by a decrease in the total number of nucleated cells due to the reduced numbers
      in all cell compartments of erythroid and megakaryocytic lineage, as well as in
      the number of mature granulocytes and lymphocytes. In contrast, femoral
      granulocytic proliferative compartments, colony forming unite granulocyte
      macrophage (CFU-GM) and morphologically recognizable proliferative granulocytes
      (PG), exhibited stimulated granulopoiesis, while the number of mature monocytes
      was close to the control value. In summary, we have shown that acute T. gondii
      infection results in profound alterations of the hematopoietic system that
      markedly contribute to the clinical onset of the disease and the, ultimately
      lethal, outcome.

PMID- 12803119
TI  - Isolation of bound thrombin consisting of thrombin and fibrin N-terminal fragment
      from clot lysate.
AB  - It has been reported that thrombin is liberated from fibrin clots by the action
      of fibrinolytic enzymes. It has also been reported that the liberated thrombin
      complexes with fibrin fragment E or (DD)E, which are denoted as bound thrombin.
      However, bound thrombin has not been isolated from clot lysate, and the
      structural characteristics of isolated bound thrombin have not been specified. In
      this study, we attempted to isolate the bound thrombin from clot lysate and to
      clarify its structural features. Rabbit fibrinogen was clotted with bovine
      thrombin, and clot lysate was prepared with urokinase. The bound thrombin was
      isolated from clot lysate by serial chromatography using a Sepharose 4B column
      immobilizing an anti-bovine thrombin antibody and a Sepharose 4B column
      immobilizing an anti-rabbit fibrinogen antibody. SDS-PAGE under unreduced
      conditions demonstrated that there were two different protein bands in the
      isolated bound thrombin. On a C4 reverse-phase HPLC, the bound thrombin from clot
      lysate was resolved by 4 M urea into alpha-thrombin and a fibrin fragment, the N
      terminal regions of which were identified as alpha-, beta- and gamma-chains.
      Thus, in the bound thrombin, thrombin molecule would bind to rabbit fibrin
      fragment consisting of N-terminal central domain.

PMID- 12803120
TI  - Thrombophilic markers in patients with congenital bleeding disorders.
AB  - We have studied the presence or absence of thrombophilic markers in 59 patients
      with congenital bleeding disorders. Theoretically, the coexistence of coagulation
      factor deficiency and thrombophilia in patients with haemophilia may cause the
      bleeding tendency to decline. In 8 cases we have found thrombophilic marker
      positivity, in 7 patients APC resistance and in 1 patient protein S deficiency
      has been revealed. The presence of thrombophilic markers did not affect the
      frequency of bleeding episodes or the development of haemophilic arthropathy. The
      factor concentrate utilization, however, was lower in the group carrying
      thrombophilic markers, which indicates that the bleeding episodes were less
      severe. Relying on the strength of these findings, the medicinal influencing of
      inhibitor mechanisms may present itself as a potential therapy.

PMID- 12803121
TI  - Polymorphism analysis in the COLIA1 gene of patients with thalassemia major and
      intermedia.
AB  - beta-Thalassemia, an inherited blood disorder, mainly affects people from the
      Mediterranean region. This life-threatening anemia is so severe that regular
      blood transfusions and iron-chelating therapy is obligatory throughout life.
      Commonly occurring complications, especially in adult patients, are osteopenia
      and osteoporosis. Osteoporotic fractures are strongly associated with bone
      density, which is under polygenic control. Type I collagen, which is encoded by
      the COLIA1 and COLIA2 genes, is the major protein in the bone. A G-->T
      polymorphism in the regulatory region of the COLIA1 gene at a recognition site
      for transcription factor Sp1 has been strongly associated with osteoporotic
      fractures. In this study, the G-->T polymorphism is screened in 42 beta
      thalassemia major and 10 beta-thalassemia intermedia patients. 64.3% of the beta
      thalassemia patients were heterozygotes for G/T (Ss) polymorphism and 35.7% were
      homozygous for G/G (SS), 60% of the beta-thalassemia intermedia patients were
      heterozygous (Ss) and 40% were homozygous (ss). The number of heterozygotes in
      the beta-thalassemia major group was significantly higher, compared to the
      control group (F = 13.615, P = 0.001). The number of heterozygotes in beta
      thalassemia intermedia group was also significantly higher, compared to the
      control group (F = 5.158, P = 0.029). Patients who are G/T heterozygotes (Ss) at
      the polymorphic Sp1 site have a lower bone mineral density than G/G homozygotes
      (SS) (P = 0.01).

PMID- 12803122
TI  - Refrigerated storage decreases the white blood cell count and influences the
      stability of automated differential on the Sysmex SE-9000.

PMID- 12803123
TI  - Type I Gaucher's disease with homozygous R463C mutation without neurological
      involvement.
AB  - Gaucher's disease is an inherited glycolipid storage disorder, caused by a
      deficiency of the catabolic enzyme glucocerebrosidase. Frequently, N370S and
      L444P of mutations are observed. R463C (i.e., 1504C-->T) mutation may predict
      neurological involvement in Gaucher's disease. We report a 36-year-old Turkish
      man with type I Gaucher's disease with homozygous R463C mutation without
      neurological involvement.

PMID- 12803124
TI  - Autoimmune haemolytic anaemia as the presenting manifestation of agnogenic
      myeloid metaplasia.
AB  - We report an unusual case of a 40-year-old female patient with a severe case of
      direct Coombs positive haemolytic anaemia, moderate hepatomegaly and marked
      splenomegaly. Her initial response to steroids was transient and was rapidly
      followed by a relapse. Therefore, she underwent splenectomy both as a therapeutic
      measure and to rule out an underlying lymphoproliferative disorder.
      Histopathological examination of the excised spleen, as well a liver biopsy,
      revealed extensive extramedullary haematopoiesis, while significant marrow
      fibrosis was noted in a trephine biopsy sample. These findings confirmed the
      concomitant diagnosis of agnogenic myeloid metaplasia with myelofibrosis.

PMID- 12803125
TI  - Chronic myeloid leukemia in a patient with colon adenocarcinoma.
AB  - A 62-year-old male patient who developed Philadelphia chromosome-positive chronic
      myeloid leukemia (CML) after cisplatin and 5-fluorouracil treatment for colon
      adenocarcinoma is reported. CML has been described after therapy for other
      malignancies, but no case of CML has been reported following treatment for colon
      carcinoma. It is not clear whether the development of CML after colon
      adenocarcinoma represents a therapy-related secondary malignancy, a coincidence,
      or an increased susceptibility to secondary malignancies due to the malignant
      process itself. Here we reported a case with colon adenocarcinoma and later
      developing CML which is not reported so far in according to our knowledge.

PMID- 12803127
TI  - Rare, late complications in a patient with Hodgkin's disease.
AB  - We report a unique case of a cured Hodgkin's disease patient who developed
      several complications decades after mantle and neck radiation therapy. First on
      the right, then years later on the left side of the neck a pharyngocutaneous
      fistula developed complicated by rupture of the carotid arteries on both sides
      necessitating their ligation. The fistula on the right side was successfully
      closed by plastic surgery, but the one on the left side is still a problem as
      severe hypoperfusion of the brain limits therapeutic possibilities. We discuss
      the relationships between the treatment for Hodgkin's disease and subsequent
      complications as well as treatment of these complications.

PMID- 12803126
TI  - Severe hyperglycemia as a complication of big ICE chemotherapy in a patient with
      acute myeloblastic leukemia.
AB  - BACKGROUND: Big ICE chemotherapy (consisting of Idarubicin, high dose Cytosine
      arabinoside and Etoposide), has proven its efficacy in the treatment of patients
      with relapse/refractory acute myeloblastic leukemia. In this case report, we
      present a patient developing the complication of severe hyperglycemia following
      administration of big ICE because of a relapse of acute myeloblastic leukemia.
      CASE REPORT: When a 41-year-old woman with acute myeloblastic leukemia in relapse
      was treated using the big ICE protocol, because of lack of efficacy of other
      chemotherapy regimens. On the 7th day and 9th day of chemotherapy, glycemia was
      13.2 mmol/l and 25.8 mmol/l, respectively. Hyperglycemia was controlled with
      continuous regular insulin infusion and neutralization of parenteral nutrition
      solution with regular insulin. After the regulation of the glycemia, regular
      insulin was injected four times daily. Following days, hematological remission
      was obtained and requirement of insulin becomes less and glycemia decreased to
      the normal levels. CONCLUSION: Severe hyperglycemia/diabetes mellitus likely due
      to chemotherapy may develop in patients with acute leukemia. This may have a
      negative effect on mortality and morbidity. For this reason, these patients
      should be followed closely.

PMID- 12803128
TI  - Hepatosplenic gamma delta T-cell lymphoma with leukemic phase successfully
      treated with 2-chlorodeoxyadenosine.
AB  - An unusual case of hepatosplenic gamma delta T-cell lymphoma with leukemic phase
      in a 39-year-old woman is reported. At the first presentation she had
      splenomegaly and pancytopenia diagnosed as hypersplenia treated by splenectomy.
      Subsequently, she developed hepatomegaly and progressive neoplastic
      lymphocytosis. The bone marrow showed a sinusoidal infiltrate of medium-sized
      cells. Flowcytometric analysis of peripheral blood mononuclear cells demonstrated
      expression of CD3, CD7, CD16, CD56 antigens and T-cell receptor gamma delta. A
      monoclonal TCR gamma- and beta-chain gene rearrangement were detected by
      polymerase chain reaction. The patient was treated by traditional chemotherapy
      and alpha-interferon, unsuccessfully. Therefore, 2-chlorodeoxyadenosine was
      introduced resulting in a complete remission for 6 months. The reported case
      demonstrates the usefulness of 2-chlorodeoxyadenosine in treatment of
      hepatosplenic gamma delta T-cell lymphoma.

PMID- 12803129
TI  - Vena cava superior syndrome due to sternal plasmacytoma in the course of systemic
      myeloma.
AB  - Here we present a patient with multiple myeloma course. The first clinical
      manifestation was superior vena cava syndrome due to a huge sternal plasmocytoma.
      The patient was treated with a combination of high dose radiotherapy and
      autologous peripheral blood stem cell transplantation. We suggest careful
      evaluation of these patients with respect to aggressive therapy.

PMID- 12803130
TI  - Angiocentric lymphomatoid granulomatosis and severe hypogammaglobulinaemia.
AB  - Angiocentric lymphomatoid granulomatosis is a rare lymphoproliferative disease,
      mainly associated with pulmonary manifestation. Its origin is unknown, but
      Epstein-Barr virus may be one of the etiological factors. A 51-year-old male had
      an abdominal laparotomy in 1994 and a large granulomatous mass was removed from
      behind the cecum. No specific therapy was administered. In February 1998 multiple
      pulmonary lesions were found by X-ray and thoracoscopic biopsy was made. The
      histopathological diagnosis was angiocentric lymphomatoid granulomatosis. The
      patient received 6 cycles of CHOP chemotherapy, with which a complete remission
      was achieved. A consistent severe hypogammaglobulinaemia was detected, so the
      diagnosis of common variable immunodeficiency (CVID) was established. The
      diagnosed CVID was the probable causative factor of the angiocentric lymphomatoid
      granulomatosis. After the CHOP treatment, the patient is on intravenous
      immunoglobulin substitution and is well up to today.

PMID- 12803131
TI  - Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in
      three Indian families.
AB  - Congenital methemoglobinemia is a relatively rare clinical disorder characterized
      by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or
      deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH
      MR). NADH-MR deficiency leads to two different types of recessive congenital
      methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR
      deficiency is restricted only to the red blood cells. In type II, cyanosis is
      associated with severe mental retardation and neurological impairment. The
      objective of this study is to establish the cause of cyanosis in our cases of
      congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed
      spectrophotometrically. Spectral analysis of the hemolysate treated with
      potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on
      starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR
      deficiency was detected in 3 families. There was a history of consanguinity in
      one of these cases. The three propositi presented with breathlessness, fever and
      peripheral cyanosis. There was no history of cardiac illness or exposure to drugs
      and chemicals. There were no signs and symptoms of mental retardation. The
      presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced
      glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1
      to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in
      three unrelated cases (age 4 months to 6 years) where the activity of the enzyme
      was 30-40% of normal. These three cases of congenital methemoglobinemia are due
      to type-I NADH-MR deficiency without mental retardation.

PMID- 12803132
TI  - Heterozygous methylene tetrahydrofolate reductase mutation with mild
      hyperhomocysteinemia associated with deep vein thrombosis.
AB  - Hyperhomocysteinemia is known to be associated with arterial occlusive vascular
      disease and venous thrombosis. Here we report a young ethnic Omani patient with
      recurrent venous thrombosis who was found to be heterozygous for the C677T
      mutation in the enzyme methyltetrahydrofolate reductase (MTHFR). Moderate
      hyperhomocysteinemia was also documented in the presence of normal red cell
      folate and serum B12 levels. No other marker usually associated with hereditary
      thrombophilia could be demonstrated in the patient, despite extensive
      investigations on multiple occasions.

PMID- 12803133
TI  - The use of granulocyte colony-stimulating factor in a neutropenic renal
      transplant recipient.
AB  - Leukopenia occurring after kidney transplantation is a very dangerous condition.
      It may increase the risk of severe infections which might lead to septicemia or
      may result in graft loss because the dose of immunosuppressants must be reduced,
      so it must be diagnosed and treated as soon as possible. The use of recombinant
      granulocyte colony-stimulating factor (G-CSF) in renal transplant recipients is a
      new therapeutic approach. This factor is successful in producing a rise in
      neutrophil count without adverse effect on renal function. We report the
      successful use of G-CSF in a renal transplant recipient in whom neutropenia
      developed following pulmonary fungal infection.

PMID- 12803134
TI  - Beta-alanine acts on glycine receptors in the rat sacral dorsal commissural
      neurons.
AB  - Whole-cell current responses to bath application of beta-alanine (beta-ALA) were
      investigated in neurons acutely dissociated from the rat sacra! dorsal
      commissural nucleus (SDCN) using the nystatin perforated patch recording
      configuration under voltage-clamp conditions. beta-ALA activated inward currents
      in a concentration-dependent manner over the range of 10-3000 microM with an EC50
      of 80.8 microM. The reversal potential of beta-ALA-activated currents (I beta
      ALA) was close to the Cl- equilibrium potential. Strychnine and the chloride
      channel blocker picrotoxin suppressed the I beta-ALA in a concentration-dependent
      manner with the IC50 values of 0.19 microM and 343.6 microM, respectively. At the
      concentration of 3 microM, strychnine was sufficient to completely block 100
      microM beta-ALA response, whereas it did not show a suppression of GABA response.
      In contrast, bicuculline, a potent GABAA receptor antagonist, at concentrations
      up to 10 microM, a dose that could block the GABA response completely, had little
      or no effect on I beta-ALA. Furthermore, the I beta-ALA was not affected by a
      preceding GABA response, but rather cross-desensitized with that evoked by
      glycine. The results indicate that beta-ALA activates the strychnine-sensitive
      glycine receptors in the SDCN neurons, and suggest that beta-ALA may act as a
      functional neurotransmitter in the mammalian SDCN.

PMID- 12803135
TI  - Cortical dysplasia, temporal atrophy, mental retardation, dysmorphic facies, and
      partial epilepsy: an EEG and dynamic susceptibility contrast (DSC) MRI study in a
      new possible genetic syndrome.
AB  - We report the case of a 24-year-old female with partial epilepsy, mental
      retardation, and dysmorphic facies. In EEG, a high spiking rate (HSR) was evident
      with abnormalities in the right frontal region. Morphological MRI showed a left
      temporo-mesial sclerosis and a cortical dysplasia localized in the right frontal
      cortex. Dynamic susceptibility contrast (DSC) MRI showed hyperperfusion in right
      frontal region and hypoperfusion in left fronto-temporal region. Left fronto
      temporal hypoperfusion is consistent with temporo-mesial sclerosis. Right frontal
      hyperperfusion is related to the cortical dysplasia area with HSR. HSR may
      resemble both electroencephalographic and perfusional ictal pattern. DSC MRI is
      useful in the evaluation of regions involved in the genesis of ictal and
      interictal epileptiform activity. Furthermore, we hypothesize that our patient
      would be affected by a new possible genetic syndrome.

PMID- 12803136
TI  - Effects of exercise on somatosensory-evoked potentials.
AB  - The aim of this study was to investigate the effect of acute and regular exercise
      on somatosensory-evoked potentials (SEP). The study group was designed as 9
      female and 7 male volleyball players, and the control group as 9 female and 7
      male sedentary students. The P1 and P2 latency and amplitude values were measured
      by tibial nerve stimulation on both lower extremities in the study groups before
      and after exercise on a treadmill. Intra-group comparison was made to evaluate
      the acute effects of exercise, and inter-group comparison for the chronic effects
      of it. Statistically significant difference was determined in pre-exercise right
      P2 amplitudes and post-exercise left P2 latencies of female volleyball players
      and sedentary girls. There was significant difference between only the pre
      exercise left P2 latency when comparison was made between the sportsmen and
      sedentary male subject groups. There were significant differences between the pre
      exercise left P1 and P2 latency values of sportswomen and right P2 amplitudes of
      sedentary female subjects. There was no significant difference between left P2
      latency values of sportsmen and sedentary male subjects. In conclusion, it was
      determined that acute and regular exercise shortened the latency of sensory
      evoked potentials while decreasing their amplitudes. When evaluating the sensory
      evoked potentials in electrophysiology laboratories, the exercise capacity and
      physical activity levels of the subjects should be considered.

PMID- 12803137
TI  - Fiber structure of optic nerve in cadmium-exposed diabetic rats: an
      ultrastructural study.
AB  - This study aimed to show ultrastructural effects of diabetes and cadmium on the
      optic nerve. We used 52 healthy Swiss albino male rats. They were divided into
      four groups: control (C), diabetic (D), cadmium, (Cd), and diabetic with cadmium
      (D + Cd). The diabetic condition was created by intravenous injection of 5 mg
      alloxan/100 g. Intraperitoneal CdCl2(2 mg kg/week) was given to Cd and D + Cd
      groups for two months. At the end of the experimental period, animals were
      sacrificed and the optic nerves were dissected at the front level of chiasma
      opticum. The tissue samples were investigated by using light and electron
      microscopic techniques. It was found that both diabetes and Cd intoxication cause
      myelin disorganization and organelle destruction in axoplasm and cytoplasm of
      glia. The results suggested that Cd increases the oxidative stress induced by
      diabetes, by disturbing some enzymatic mechanisms.

PMID- 12803138
TI  - Hypothalamic digoxin and hemispheric chemical dominance--relation to the
      pathogenesis of senile osteoporosis, degenerative osteoarthritis, and
      spondylosis.
AB  - The isoprenoid pathway produces three key metabolites: i) digoxin (a membrane
      sodium-potassium ATPase inhibitor which can regulate intracellular
      calcium/magnesium ratios), ii) dolichol (which regulates N-glycosylation of
      proteins), and iii) ubiquinone (a free radical scavenger), all of which are
      important in bone and joint metabolism. The pathway was assessed in senile
      osteoporosis, spondylosis, and osteoarthritis. Digoxin could possibly play a role
      in the genesis of cerebral dominance because it can regulate multiple
      neurotransmitter systems. The pathway was also assessed in individuals of
      differing hemispheric dominance for comparison and to find out the role of
      cerebral dominance in the pathogenesis of these diseases. The plasma/serum
      activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, and
      tryptophan/tyrosine catabolic patterns, as well as RBC Na(+)-K+ ATPase activity,
      were measured in the above mentioned groups. The glycoconjugate metabolism, free
      radical metabolism, and membrane composition were also studied. The pathway was
      upregulated with increased digoxin synthesis in patients with spondylosis and
      osteoarthritis. In this group of patients, the glycoconjugate levels and dolichol
      levels were increased and lysosomal stability reduced. The ubiquinone levels were
      low and free radicals increased in spondylosis and osteoarthritis. On the other
      hand, in senile osteoporosis, the isoprenoid pathway was downregulated and
      digoxin synthesis reduced. The glycoconjugate and dolichol levels were low and
      lysosomal stability increased. The ubiquinone levels were increased and free
      radical production increased in senile osteoporosis. The significance of these
      changes in the pathogenesis of osteoarthritis, spondylosis, and osteoporosis is
      discussed. The hyperdigoxinemic state is seen in osteoarthritis and spondylosis
      and in right hemispheric dominance. The hypodigoxinemic state is seen in left
      hemispheric dominance and senile osteoporosis. Hemispheric dominance plays a
      crucial role in deciding the predisposition to bone and joint diseases. Right
      hemispheric chemical dominance predisposes to spondylosis and osteoarthritis.
      Left hemispheric chemical dominance predisposes to osteoporosis.

PMID- 12803140
TI  - Hypothalamic digoxin, hemispheric chemical dominance, and spirituality.
AB  - The isoprenoid pathway was assessed in atheistic and spiritually inclined
      individuals. The pathway was also assessed in individuals with differing
      hemispheric dominance to assess whether hemispheric dominance has a correlation
      with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin,
      RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan
      catabolic patterns were assessed in spiritual/atheistic individuals and in those
      differing hemispheric dominance. In spiritually-inclined individuals, there was
      increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity,
      increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and
      decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The
      pattern in spiritually-inclined individuals correlated with right hemispheric
      chemical dominance. In atheistic individuals there was decreased digoxin
      synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan
      catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine
      catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic
      individuals correlated with that obtained in left hemispheric chemical dominance.
      Hemispheric chemical dominance and hypothalamic digoxin could regulate the
      predisposition to spirituality or atheism.

PMID- 12803139
TI  - Hypothalamic digoxin, hemispheric chemical dominance, and Alzheimer's disease.
AB  - This study assessed the changes in the isoprenoid pathway and the consequences of
      its dysfunction in Alzheimer's disease (AD). The isoprenoid pathway and digoxin
      status were also studied for comparison in individuals of differing hemispheric
      dominance to find the role of cerebral dominance in the genesis of Alzheimer's
      disease. There was elevation in plasma HMG CoA reductase activity, serum digoxin,
      and dolichol levels, and a reduction in serum magnesium, RBC membrane Na(+)-K+
      ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin,
      strychnine, nicotine, and quinolinic acid were elevated, while serum tyrosine,
      morphine, dopamine, and noradrenaline were decreased. The total serum
      glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading
      enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum
      glycolipids were elevated in Alzheimer's disease. HDL cholesterol was reduced and
      free fatty acids increased. The RBC membrane glycosaminoglycans, hexose, and
      fucose residues of glycoproteins and cholesterol were reduced, while phospholipid
      increased. The activity of all free radical scavenging enzymes, concentration of
      glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased
      significantly in Alzheimer's disease, while the concentration of lipid
      peroxidation products and NO increased. The hypomagnesemia-related NMDA
      excitotoxicity, ubiquinone deficiency related mitochondrial dysfunction, and
      altered glycoconjugates/lysosomal stability could contribute to the pathogenesis
      of Alzheimer's disease. The biochemical patterns, including hyperdigoxinemia
      observed in Alzheimer's disease, correlated with those obtained in right
      hemispheric chemical dominance. Right hemispheric chemical dominance is a
      predisposing factor for Alzheimer's disease.

PMID- 12803141
TI  - Executive function in young Colombian adults.
AB  - The aim of this article was to observe the correlation between executive function
      (EF) variables, and to determine the factor structure of the EF in young
      university students, as mathematical models for supporting its multidimensional
      structure. Participants were both males and females, aged 16 to 21 years (N =
      100) and with normal Full Scale IQ selected in a randomized and representative
      approach in private universities of Medellin, Colombia. They were students of
      verbal, visual-spatial, and mathematical careers. An executive function
      assessment battery was applied and which included: Wisconsin Card Sorting Test
      (WCST), Trail Making Test (TMT) A and B, verbal fluency test (FAS) by phonologic
      and semantic cues, and Stroop's conflict word/color test. The results were as
      follows: An orthogonal structure of five factors, which explained 74.9% of the
      variance, was found. Factor 1 was formed by WCST variables (organization and
      flexibility), and explained 25.8% of the variance. Errors from the Stroop reading
      and naming were assigned to factor 2, which explained 17.3% of the variance.
      Factor 3 was the time for executing Stroop's test, and explained 13.1% of the
      variance. Factor 4 was TMT A and B (10.1%). Factor 5 was verbal fluency (8.5% of
      the variance). In conclusion, executive function in young university students was
      conformed by five orthogonal cognitive dimensions.

PMID- 12803142
TI  - Sex and handedness differences in hearing durations of the right and left ears in
      healthy young adults.
AB  - The aim of this work was to study the sex and handedness differences in hearing
      durations of the right and left ears in healthy young adults. The hearing
      durations were assessed using a modified Rinne test. The hearing durations of
      both the right and left ears were longer in males than females. In right-handers,
      the hearing duration of the right ear was longer than that of the left ear; in
      left-handers, the hearing duration of the left ear was longer than that of the
      right ear. These results suggest a male superiority in auditory perceptual
      acuity; a left-ear advantage in left-handers may result in the superiority of non
      right-handers in musical tasks.

PMID- 12803143
TI  - Utility analysis for clinical decision-making in small treatment settings.
AB  - Data-driven clinical decision-making can be difficult in settings that service
      relatively few patients because of the small samples available, the patients'
      potential dissimilarity from participants in published research, and highly
      limited resources. This study was designed to demonstrate how utility analyses
      might assist clinical decision-making in small treatment settings and provide
      data for promoting programmatic improvements. Data came from a study to identify
      rural juvenile delinquents suspected to not benefit from residential behavioral
      treatment. A prospective correlational design was used with data from a
      midwestern juvenile criminal justice residential unit in which about 30 males
      were treated annually. Outcomes included treatment performance measures and
      number of delinquent offenses during the year after treatment. Utility analyses
      suggested that delinquents who were less likely to benefit from residential
      treatment could be identified a priori using a modified Psychopathy Checklist,
      Revised. Cost utility analysis estimated $180,000 less would be spent on
      residential treatment as a result of selecting residents based on the
      pretreatment assessment. This money might be reallocated toward alternative
      intervention for delinquents who are not likely to benefit from the residential
      treatment. More importantly, results suggested specific alternative interventions
      for the delinquents who were less likely to benefit from the treatment by
      providing direct links to existing literature. Advantages of utility analysis
      research include strong external validity, minimal interference with treatment
      during data collection, results that estimate clinical and practical
      significance, and results that are easily communicated to laymen.

PMID- 12803144
TI  - Effects of serial visuomotor tasks on contingent negative variation.
AB  - We evaluated contingent negative variation (CNV) in 15 right-handed normal
      subjects who performed simple finger extension(NB) or skilled finger movement
      task with visual guidance (B). When subjects performed serial tasks of NB-B1
      (first block of B)-B2 (second block of B), the CNV amplitudes were larger in BI
      compared with NB at the left frontoparietal leads for early CNV, at widely
      distributed areas for the middle CNV and at the left frontopatietal and right
      frontal leads for late CNV. The present results suggest that the frontoparietal
      area involving the prefrontal and sensorimotor cortices, plays an important role
      in visuomotor learning.

PMID- 12803145
TI  - Protecting the smallest among us.

PMID- 12803146
TI  - Preparing a female collegiate athlete for anterior cruciate ligament
      reconstruction and rehabilitation.
AB  - An anterior cruciate ligament injury is common among athletes involved in sports
      where cutting or sudden changes of position occur. This is a case study of a
      female collegiate athlete who sustained an anterior cruciate ligament injury,
      with a small meniscus tear, and decides on a course of surgery. Questions she has
      about the initial injury, as well as subsequent questions concerning
      reconstructive surgery using a patellar graft and the course of rehabilitation,
      are answered. A chart of her rehabilitation protocol is provided.

PMID- 12803147
TI  - Life satisfaction and its correlates in older women with osteoarthritis.
AB  - PURPOSE: To identify the relationships among functional disability, chronic daily
      stress, coping strategies, beliefs about personal control, social support, and
      life satisfaction in older women with osteoarthritis. DESIGN: A descriptive,
      correlational design was used. SAMPLE: The study participants were 107 women aged
      60 years or older. METHOD: Study participants completed six survey questionnaires
      and a demographic form. FINDINGS: Bivariate correlational analyses showed that
      older women with poorer functional ability experienced greater chronic daily
      stress, reported more frequent use of emotion-focused coping strategies, and had
      a higher chance health locus of control. A hierarchic regression analysis
      revealed that the perceived social support and internal health locus of control
      significantly contributed to the prediction of life satisfaction after
      demographic, illness-related, and stress-related variables were controlled.
      IMPLICATIONS: Stress management strategies matched to the participants' style of
      coping process can increase their sense of control over their health and enhance
      their social networks and activities.

PMID- 12803148
TI  - Heart failure management in the elderly postoperative patient.
AB  - As the population ages, the elderly will account for a significant portion of
      surgical cases. These patients have age-related cardiovascular changes and can
      suffer from multiple chronic disease conditions. Congestive heart failure is a
      chronic condition that afflicts nearly five million Americans. It is the most
      common diagnosis among patients 65 years or older, with 8% to 10% of senior
      citizens having this chronic disease. A comprehensive understanding of the
      pathophysiology, assessment, and management strategies of congestive heart
      failure will give the orthopaedic nurse the knowledge needed to help minimize the
      morbidity and mortality associated with this disease.

PMID- 12803149
TI  - Shaken baby syndrome.
AB  - Shaken baby syndrome is a significant cause of infant morbidity and mortality and
      is widely recognized in the medical literature. Classic signs include retinal
      hemorrhage, subdural or subarachnoid hemorrhage, and associated fractures. Most
      victims are younger than 6 months old and have been affected by violent shaking
      with rapid angular deceleration and possible terminal impact. This article
      summarizes issues related to clinical presentation, diagnosis, risk factors, and
      interventions for healthcare professionals.

PMID- 12803151
TI  - A comprehensive review of spinal arachnoiditis.
AB  - Spinal arachnoiditis is an insidious disease caused by an inflammatory process of
      the arachnoid membrane resulting from many possible causes, such as myelograms
      with oil-based radiographic contract agents and multiple back surgeries.
      Diagnosis is based on symptoms and magnetic resonance imaging. Arachnoiditis can
      also mimic the symptoms of other diseases, such as spinal cord tumors, cauda
      equina syndrome, arachnoiditis ossificans, and syringomyelia. Unfortunately,
      there is no cure, only treatment of the chronic symptoms. It is an incurable
      disease that can cause minor to severe symptoms from unexplained rashes to
      neurologic defects.

PMID- 12803150
TI  - Uncertainty in illness. An integrative review.
AB  - The purpose of this article is to report an integrative review of uncertainty in
      the illness experience, describe the uncertainty in illness theory, and to
      discuss the importance of assessing the appraisal of uncertainty experienced in
      illness with individuals and families faced with illness.

PMID- 12803152
TI  - Tired blood. Part 1.
AB  - "Tired blood" is a common term used to describe anemia because of the association
      between fatigue, often the first sign of anemia, and the idea that it has
      "something to do with blood." Today, millions of people have diagnosed anemia,
      and millions more with chronic diseases are at risk for developing anemia. Anemia
      is not a specific disease; rather, it is an indication that something has either
      disturbed the maturation of essential red blood cells or interfered with the
      oxygen carry capacity of red cells. In this two-part series about tired blood,
      the etiology and pathophysiology of selected forms of anemia are discussed and
      pharmacotherapy designed to address the condition of anemia is identified. Part 1
      addresses anemia related to red blood cell development, and Part 2 explores the
      physiology of hemoglobin-related anemia and inherited anemia.

PMID- 12803153
TI  - Lumbar herniated nucleus pulposus.

PMID- 12803154
TI  - Certified practice: we owe it to our patients and ourselves.

PMID- 12803155
TI  - Nurse camp for a cause.

PMID- 12803156
TI  - Safe, secure staff provides better care.

PMID- 12803157
TI  - Point-of-care testing: not always waived.
AB  - Learn what the Joint Commission's standards require of waived testing and how
      it's regulated by organizational policy.

PMID- 12803158
TI  - New rules keep EMTALA in check.
AB  - Recently proposed rules on the interpretation of EMTALA maintain the law's
      intention while protecting staff by limiting its ever-increasing application.

PMID- 12803159
TI  - Number crunching with variable budgets.
AB  - Variable budgeting allows managers to support a resource management plan that
      provides for efficient staffing and patient care.

PMID- 12803160
TI  - Every breath you take.
AB  - Recent advancements to ventilators and interface choices have increased
      noninvasive positive pressure ventilation usage in long-term and intensive care
      settings.

PMID- 12803161
TI  - A new assessment tool: fetal oxygen saturation monitoring.
AB  - Pulse oximetry technology enables clinicians to obtain intrauterine fetal oxygen
      saturation levels.

PMID- 12803162
TI  - Magnet status attracts Russia.
AB  - Follow the efforts of Moscow's Central Clinical Hospital as it prepares a project
      demonstration for the Magnet Nursing Services Recognition Program of the American
      Nurses Credentialing Center.

PMID- 12803163
TI  - Cut the clutter with cycle time reduction.
AB  - Users of cycle time reduction create process maps to identify and eliminate
      wasted resources. Consider implementing a similar process to streamline your
      facility's nursing model.

PMID- 12803164
TI  - Solve the policy and procedure puzzle.
AB  - Explore the merits of forming a multidisciplinary policy and procedure team to
      simplify processes.

PMID- 12803165
TI  - New frequencies, new monitoring technology.
AB  - Regulatory changes in available frequencies for wireless patient monitoring
      require many hospitals to implement new monitoring systems. Choose the best
      features of current technology, while allowing for future advances in both on-
      and off-site patient monitoring.

PMID- 12803166
TI  - From classroom to CCU.
AB  - Consider these issues when hiring new nurses into positions usually reserved for
      seasoned staff.

PMID- 12803167
TI  - Building dream teams.

PMID- 12803168
TI  - Risk for fracture in women with low serum levels of thyroid-stimulating hormone.
AB  - BACKGROUND: Biochemical evidence of hyperthyroidism may be associated with low
      bone mass, particularly in older postmenopausal women, but no prospective studies
      of thyroid function and subsequent fracture risk have been done. OBJECTIVE: To
      examine the association between low levels of thyroid-stimulating hormone (TSH)
      and fracture in older women. DESIGN: Prospective cohort study with case-cohort
      sampling. SETTING: Four clinical centers in the United States. PATIENTS: 686
      women older than 65 years of age from a cohort of 9704 women recruited from
      population-based listings between 1986 and 1988. MEASUREMENTS: Baseline
      assessment of calcaneal bone mass, spine radiography, and history of thyroid
      disease. Spine radiography was repeated after a mean follow-up of 3.7 years;
      nonspine fractures were centrally adjudicated. Thyroid-stimulating hormone was
      measured in sera obtained at baseline from 148 women with new hip fractures, 149
      women with new vertebral fractures, and a subsample of 398 women randomly
      selected from the cohort. RESULTS: After adjustment for age, history of previous
      hyperthyroidism, self-rated health, and use of estrogen and thyroid hormone,
      women with a low TSH level (0.1 mU/L) had a threefold increased risk for hip
      fracture (relative hazard, 3.6 [95% CI, 1.0 to 12.9]) and a fourfold increased
      risk for vertebral fracture (odds ratio, 4.5 [CI, 1.3 to 15.6]) compared with
      women who had normal TSH levels (0.5 to 5.5 mU/L). After adjustment for TSH
      level, a history of hyperthyroidism was associated with a twofold increase in hip
      fracture (relative hazard, 2.2 [CI, 1.0 to 4.4]), but use of thyroid hormone
      itself was not associated with increased risk for hip fracture (relative hazard,
      0.5 [CI, 0.2 to 1.3]). CONCLUSIONS: Women older than 65 years of age who have low
      serum TSH levels, indicating physiologic hyperthyroidism, are at increased risk
      for new hip and vertebral fractures. Use of thyroid hormone itself does not
      increase risk for fracture if TSH levels are normal.

PMID- 12803169
TI  - Advancing HIV prevention: new strategies for a changing epidemic--United States,
      2003.

PMID- 12803170
TI  - Proceedings of the Meeting of Geriatric Endocrinology. Parma, Italy. November 12
      13, 2001.

PMID- 12803171
TI  - Evidence-based haemostasis. Proceedings of a symposium. Dublin, Ireland. November
      9-11, 2001.

PMID- 12803172
TI  - Treatment and final disposition of health care waste has increased considerably
      during the past few years.

PMID- 12803173
TI  - The signal and the trap: targeted delivery and retention of proteins in the
      mitochondrion.

PMID- 12803174
TI  - Cancer gene therapy: lessons learned from experiences with chemotherapy.

PMID- 12803175
TI  - Febrile respiratory tract illness in a 3-month old infant.

PMID- 12803176
TI  - Proceedings of the Health, Communication, and Aging Research Symposium on Cancer
      Communication. George Mason University, Fairfax, Virginia, USA. February, 2002.

PMID- 12803177
TI  - Proceedings of the Scientific Symposium on Vaccination against Influenza. Kemi,
      Finland. March 22, 2002.

PMID- 12803178
TI  - Nutrition as a preventative strategy against adverse pregnancy outcomes.
      Proceedings of a consultative meeting. Oxford, United Kingdom. July 18-19, 2002.

PMID- 12803179
TI  - Abstracts of the 18th Meeting of the European Intestinal Transport Group. Egmond
      aan Zee, The Netherlands. September 28-October 1, 2002.

PMID- 12803180
TI  - Complementary/alternative medicine in gynecology: no simple messages please!

PMID- 12803181
TI  - Hypoglycemia 2001: from research to practice. Proceedings of a symposium. Assisi,
      Italy. May 26-29, 2001.

PMID- 12803183
TI  - Abstracts of the Third Conference on Stem Cell Gene Therapy: biology and
      technology. Rockville, Maryland, USA. March 21-23, 2002.

PMID- 12803182
TI  - Abstracts of the III International Conference on Familial Mediterranean Fever and
      Hereditary Inflammatory Disorders. Montpellier, France. September 2002.

PMID- 12803184
TI  - [Medicine from the greenhouse?].

PMID- 12803185
TI  - [Can an intracranial aneurysm burst through an outside influence?].

PMID- 12803186
TI  - [Should a diabetic diet contain sugar?].

PMID- 12803187
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 12803188
TI  - National Hormone and Peptide Program. National Institute of Diabetes and
      Digestive and Kidney Diseases. Peptide hormones, subunits, antisera & other
      reagents available.

PMID- 12803189
TI  - Estrogens: molecular and clinical aspects in health and disease. Proceedings of
      the congress "Estrogen 2001." Modena, Italy. May 21-22, 2001.

PMID- 12803190
TI  - Abstracts from the XXXIV Annual Meeting of the Argentine Association of
      Experimental Pharmacology. Tandil, Argentina. November 24-27, 2002.

PMID- 12803191
TI  - Multistate outbreak of monkeypox--Illinois, Indiana, and Wisconsin, 2003.
AB  - CDC has received reports of patients with a febrile rash illness who had close
      contact with pet prairie dogs and other animals. The Marshfield Clinic,
      Marshfield, Wisconsin, identified a virus morphologically consistent with a
      poxvirus by electron microscopy of skin lesion tissue from a patient, lymph node
      tissue from the patient's pet prairie dog, and isolates of virus from culture of
      these tissues. Additional laboratory testing at CDC indicated that the causative
      agent is a monkeypox virus, a member of the orthopoxvirus group. This report
      summarizes initial descriptive epidemiologic, clinical, and laboratory data,
      interim infection-control guidance, and new animal import regulations.

PMID- 12803192
TI  - HIV testing--United States, 2001.
AB  - As of December 2001, a cumulative total of 816,149 cases of acquired
      immunodeficiency syndrome (AIDS) had been reported to CDC (1). One of CDC's
      national human immunodeficiency virus (HIV)--prevention goals for 2005 (Goal 2)
      is to increase the proportion of HIV-infected persons in the United States who
      know they are infected from an estimated 70% to 95% (2). A goal of the new CDC
      initiative, Advancing HIV Prevention: New Strategies for a Changing Epidemic, is
      to ensure that every HIV-infected person has the opportunity to be tested and has
      access to state-of-the-art medical care and prevention services needed to prevent
      HIV transmission (3). To characterize the prevalence of HIV-antibody testing
      among U.S. adults, CDC analyzed data from the 2001 Behavioral Risk Factor
      Surveillance System (BRFSS). The findings document variability in HIV testing
      prevalence by area and by sex within areas, underscoring the ongoing need to
      promote voluntary HIV counseling and testing that will provide persons with early
      knowledge of their HIV status and offer them access to appropriate counseling and
      treatment.

PMID- 12803193
TI  - Varicella-related deaths--United States, 2002.
AB  - Varicella is a vaccine-preventable disease that can be fatal. During 2002, state
      health departments notified CDC about nine fatal cases of varicella in adults and
      children. This report summarizes clinical data for one adult and one child,
      reported from Kansas and Illinois, respectively. Both patients were susceptible,
      unvaccinated, and exposed to unvaccinated children with varicella. These deaths
      highlight the importance of implementing strategies recommended for varicella
      disease prevention (1,2), including child care and school vaccination
      requirements, and underscore the need for improving varicella death surveillance.

PMID- 12803194
TI  - Update: severe acute respiratory syndrome--Toronto, Canada, 2003.
AB  - Severe acute respiratory syndrome (SARS) was first recognized in Toronto in a
      woman who returned from Hong Kong on February 23, 2003 (1). Transmission to other
      persons resulted subsequently in an outbreak among 257 persons in several Greater
      Toronto Area (GTA) hospitals. After implementation of provincewide public health
      measures that included strict infection-control practices, the number of
      recognized cases of SARS declined substantially, and no cases were detected after
      April 20. On April 30, the World Health Organization (WHO) lifted a travel
      advisory issued on April 22 that had recommended limiting travel to Toronto. This
      report describes a second wave of SARS cases among patients, visitors, and health
      care workers (HCWs) that occurred at a Toronto hospital approximately 4 weeks
      after SARS transmission was thought to have been interrupted. The findings
      indicate that exposure to hospitalized patients with unrecognized SARS after a
      provincewide relaxation of strict SARS control measures probably contributed to
      transmission among HCWs. The investigation underscores the need for monitoring
      fever and respiratory symptoms in hospitalized patients and visitors,
      particularly after a decline in the number of reported SARS cases.

PMID- 12803195
TI  - [Hemorrhagic stroke antithrombotic drugs].

PMID- 12803196
TI  - Update: severe acute respiratory syndrome--United States, June 11, 2003.
AB  - CDC continues to work with state and local health departments, the World Health
      Organization (WHO), and other partners to investigate cases of severe acute
      respiratory syndrome (SARS). This report updates SARS cases reported worldwide
      and in the United States, and describes the eighth probable U.S. SARS case with
      laboratory evidence of SARS-associated coronavirus (SARS-CoV) infection.

PMID- 12803197
TI  - Surveillance data from swimming pool inspections--selected states and counties,
      United States, May--September 2002.
AB  - Swimming is the second most popular exercise activity in the United States, with
      approximately 360 million annual visits to recreational water venues (1). This
      exposure increases the potential for the spread of recreational water illnesses
      (RWIs) (e.g., cryptosporidiosis, giardiasis, and shigellosis). Since the 1980s,
      the number of reported RWI outbreaks has increased steadily (2). Local
      environmental health programs inspect public and semipublic pools periodically to
      determine compliance with local and state health regulations. During inspections
      for regulatory compliance, data pertaining to pool water chemistry, filtration
      and recirculation systems, and management and operations are collected. This
      report summarizes pool inspection data from databases at six sites across the
      United States collected during May 1--September 1, 2002. The findings underscore
      the utility of these data for public-health decision making and the need for
      increased training and vigilance by pool operators to ensure high-quality
      swimming pool water for use by the public.

PMID- 12803199
TI  - Progress toward poliomyelitis eradication--Southern Africa, 2001-March 2003.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis
      globally, substantial progress has been made in all World Health Organization
      (WHO) regions, and three regions (Americas, European, and Western Pacific) are
      classified as polio-free. The African Region comprises four epidemiologic blocks
      (Central, Eastern, Southern, and Western). The Southern African block comprises
      14 countries--10 on the mainland (Angola, Botswana, Lesotho, Malawi, Mozambique,
      Namibia, South Africa, Swaziland, Zambia, and Zimbabwe) and four in the Indian
      Ocean (Comoros, Madagascar, Mauritius, and Seychelles)--with a combined total
      population in 2002 of approximately 120 million persons. This report summarizes
      polio eradication efforts in the Southern African block during January 2001-March
      2003, which indicate the possible interruption of wild poliovirus (WPV)
      transmission and underscore the need to sustain polio eradication efforts.

PMID- 12803198
TI  - Update: influenza activity--United States and worldwide, 2002-03 season, and
      composition of the 2003-04 influenza vaccine.
AB  - In collaboration with the World Health Organization (WHO), its collaborating
      laboratories, state and local health departments, health-care providers, and
      vital statistic registries, CDC conducts surveillance to monitor influenza
      activity and to detect antigenic changes in the circulating strains of influenza
      viruses. During the 2002-03 influenza season, influenza A (H1), A (H3N2), and B
      viruses co-circulated in the Northern Hemisphere. Human infections with avian
      influenza A (H5N1) and A (H7N7) viruses were reported in Hong Kong and the
      Netherlands, respectively. In the United States, the 2002-03 influenza season was
      mild; influenza A (H1) and B viruses circulated widely, and the predominant virus
      varied by region and time of season. This report summarizes influenza activity in
      the United States and worldwide during the 2002-03 influenza season and describes
      the composition of the 2003-04 influenza vaccine.

PMID- 12803200
TI  - Update: severe acute respiratory syndrome--United States, June 4, 2003.
AB  - CDC continues to work with state and local health departments, the World Health
      Organization (WHO), and other partners to investigate cases of severe acute
      respiratory syndrome (SARS). This report updates SARS cases reported worldwide
      and in the United States and summarizes changes in CDC's recommendations for
      travel to Singapore and Hong Kong and the resulting modification to the interim
      U.S. case definition for SARS.

PMID- 12803201
TI  - [Third cranial nerve palsy and Legionnaire's disease].

PMID- 12803202
TI  - [Sensory re-innervation in implants of the digits].

PMID- 12803203
TI  - [Degree of independence and cost of ischaemic stroke].

PMID- 12803204
TI  - [Is it necessary to do arteriography before indicating carotid endarterectomy?].

PMID- 12803205
TI  - [Cognitive impairment, clinic forms and progression in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis-related cognitive impairment is an important
      clinical dimension of the disease by virtue of its prevalence and its functional
      significance. It is directly related to cerebral multiple sclerosis pathology,
      but relatively independent of physical impairment. DEVELOPMENT: Thus, the
      assessment of neuropsychologic outcomes complements the assessment of physical
      outcomes in multiples sclerosis clinical trials. Neuropsychologic measures
      fulfill most of the criteria identified for an optimal multiple sclerosis
      clinical outcome measure. Major drawbacks to their current use in assessing
      clinical trial outcomes are the heterogeneity inherent in neuropsychological test
      performance(both cross-sectionally and longitudinally), and limitations in our
      knowledge about the evolution of multiple sclerosis- related cognitive impairment
      and the psychometric properties of specific measures over time. At this point in
      time, we cannot identify the single "best" measure for assessing neuropsychologic
      change in multiple sclerosis patients, and we cannot specify what constitutes
      clinically significant change. Analyses of neuropsychologic data from recently
      completed trial will soon provide an empirical basis for selecting measures to
      use in future multiple sclerosis clinical trials and specifying criteria for
      clinically significant change on these measures.

PMID- 12803206
TI  - The side effects of incompetency labeling and the implications for mental health
      law.
AB  - In addition to labeling people as mentally ill, the law often labels them as
      incompetent to exercise certain rights or to play particular roles. Indeed, under
      the broad dicta of Zinermon v. Burch, incompetency labeling may increase
      dramatically. This article uses principles of social and cognitive psychology to
      examine the effects of incompetency labeling. Such labeling is shown to produce
      potentially serious adverse effects. It often alters the way others view and
      react to the labeled individual and affects his or her self-esteem and self
      concept in ways that may inhibit performance, diminish motivation, and depress
      mood. After analyzing those negative side effects of incompetency labeling, the
      article examines the implications of these findings for mental health law and
      makes a number of proposals for changing the law in order to avoid or minimize
      these adverse effects.

PMID- 12803207
TI  - Therapeutic jurisprudence and the civil rights of institutionalized mentally
      disabled persons: hopeless oxymoron or path to redemption?
AB  - This article examines, from a therapeutic jurisprudence (TJ) perspective, the
      rights of institutionalized mentally disabled persons to determine whether TJ is
      compatible with positions advancing civil rights and liberties, and whether
      lawyers for such individuals should look more closely to TJ as a source of
      rights. It concludes (a) that despite harsh criticisms of mental disability law
      reform, most of the important decisions in the areas of involuntary civil
      commitment, right to treatment, and right to refuse treatment law have a strong
      TJ component and (b) that TJ analyses may be the appropriate tool to reinvigorate
      this area of mental disability law.

PMID- 12803208
TI  - Foreword: planning for the future through advance directive instruments.
AB  - The Foreword traces the development of advance directive instruments and
      discusses their legal enforceability and many benefits. Despite their advantages,
      advance directives remain underused and are frequently ignored by service
      providers. The contributors to this special issue discuss why this is so and
      offer and debate a variety of remedial proposals. They analyze the various legal,
      clinical, ethical, and practical issues presented by the use of advance
      directives for health and mental health care and examine new directions in their
      application. The Foreword describes the organization of this special issue,
      summarizes the articles it contains, and comments on their significance.

PMID- 12803209
TI  - Personhood, patienthood, and clinical practice: reassessing advance directives.
AB  - This article considers 2 major critiques of advance directives and offers a
      defense to each of them. The 1st critique is philosophical in nature and
      maintains that the moral authority of an advance directive is undercut by a
      failure of personal identity to survive the loss of decisional capacity. The
      response in this article is that this critique relies on a flawed and disfavored
      concept of persons and their persistence over time. The 2nd critique, pragmatic
      in nature, argues that advance directives cannot be authoritative because the
      requisite elements of an informed consent to or refusal of treatment are rarely
      present, and many such instruments are ambiguous. The author argues that if the
      creation of advance directives, as a form of advance care planning, is made an
      integral aspect of clinical practice, many more patients will elect to execute
      directives, and those directives will not be ambiguous.

PMID- 12803210
TI  - Making advance directives meaningful.
AB  - Advance directives have been criticized as impractical and/or ineffective, but
      very little of the criticism differentiates among diverse types of advance
      directives. The thesis of this article is that carefully drawn documents can be
      effective. The inadequacy of the advance directive mechanism to date flows in
      part from documents that are too vague and uninformative. People preparing
      advance directives are usually seeking to define a level of intolerable indignity
      at which death becomes preferable. By focusing on the elements of indignity that
      commonly trouble dying persons, drafters of advance directives can prepare forms
      that are relevant and meaningful to most people. The author examines the efforts
      of some existing forms to define intolerable indignity and suggests a different
      approach. That approach is a unique values profile geared to helping people
      describe what is, for them, an intolerably deteriorated status.

PMID- 12803211
TI  - [Editorial comment: factor V Leiden mutation].

PMID- 12803212
TI  - [Editorial comment: are additional EEG leads necessary in evaluation of inferior
      myocardial infarction?].

PMID- 12803213
TI  - Celecoxib versus diclofenac and omeprazole to prevent recurrent ulcer bleeding.

PMID- 12803214
TI  - Celecoxib versus diclofenac and omeprazole to prevent recurrent ulcer bleeding.

PMID- 12803215
TI  - [Editorial comment: lipoprotein (a) and coronary artery disease].

PMID- 12803216
TI  - Durable powers of attorney as a substitute for conservatorship: lessons for
      advance directives.
AB  - The author traces the evolution of the use of durable powers of attorney and
      reviews problems of guardianship, the guardianship reform movement, and the
      advent of durable powers of attorney as a response.

PMID- 12803217
TI  - Aspirin and the prevention of colorectal cancer.

PMID- 12803218
TI  - [History of homeopathy in Hungary 1820-1990].
AB  - This article tells the story of homeopathy in Hungary. After Hahnemann's
      discovery the theory found enthusiastic followers even in Hungary. The first
      generation of homeopathic physicians (Pal Almasi Balogh, Jozsef Bakody, Gyorgy
      Forgo and others) established a successful practice, although the doctrine had
      been banned in the Habsburg Empire from 1819 onwards. Thanks to the activity of
      the so-called second generation (Ferenc Hausmann, Istvan Vezekenyi Horner)
      Hahnemann's main work, the Organon was translated into Hungarian (1830) and the
      first homeopathic hospitals were founded in Koszeg (1833) and in Gyongynos
      (1838). In 1837 the order banning homeopathical practice was removed, and in 1844
      the Hungarian Parliament decided to establish a homeopathic department at the
      University of Pest. In 1847 Dome Argenti published his extradinarily successful
      homeopathic book Homeopathic Treatment of Various Illnesses". In the 1860s a new
      generation of physicians (Tihamer Almasi Balogh, Lorant Hausmann, Abraham
      Szontagh and others) published the first Hungarian homeopathic periodicals the
      Hasonszenvi Kozlony and the Hasonszenvi Lapok and, at the same time, they founded
      the Society of Hungarian Homeopathic Physicians (1865), too. In 1870 the first
      homeopathic hospital, the Elisabethinum, opened its gates, and at the University
      of Pest two different homeopathic departments began to operate. At the end of the
      century however, homeopathy entered into a period of decline, due to the
      resistance of the conventional physicians and the successes of conventional
      medicine. Between the two World Wars only Gusztav Schimert and his circle
      substained the theory and practice in Hungary, so successfully that in 1935 the
      International League of Homeopathy held its congress in Budapest. After the
      Second World War Schimert emigrated, and homeopathy was informally banned in
      Hungary (although the practice itself survived in secrecy). The Society of
      Hungarian Homeopathical Physicians was re-established only in 1991.

PMID- 12803220
TI  - Optimal use of orders not to intervene and advance directives.
AB  - More rigorous efforts in advance care planning are required in order to tailor
      end-of-life care to the preferences of patients so that they can experience a
      satisfactory last chapter of their lives. There is need for better availability
      and tracking of advance directives, and more uniform adoption of form documents
      that can be honored in every state. The discouraging evidence of inadequate end
      of-life decision making indicates the necessity of several improvement
      strategies. In response to this need, the Council on Ethical and Judicial Affairs
      of the American Medical Association has examined this issue again and presents
      the following report and recommendations.

PMID- 12803221
TI  - Advance directives.
AB  - There is significant confusion about the topic of advance directives (ADs),
      stimulated by the increasing realization that the current AD instruments probably
      have little salutary clinical effect. The instruments themselves are almost
      certainly part of the problem. In most cases they are too simple and narrowly
      focused, and one, the Medical Directive, is pointlessly complex. Seven
      suggestions are proposed for creating more adequate AD forms. The American
      Medical Association's recent report on ADs is disappointingly superficial and
      does not usefully diagnose or suggest solutions for the problems in this area of
      clinical practice.

PMID- 12803222
TI  - When is pulmonary function test needed?

PMID- 12803223
TI  - Eliciting patient preferences in today's health care system.
AB  - The American Medical Association Council on Ethical and Judicial Affairs
      recommends that physicians discuss advance directives with their patients and the
      patients' proxies. The council could have gone further by recognizing the
      difficulties physicians will encounter in trying to implement its proposal in a
      managed health care system. There is an undeniable need for caregiver
      participation in end-of-life planning, but the health care system must recognize
      and support implementation of the council's recommendations to make that
      possible. More explicit recognition of this fact on the part of the council would
      have helped physicians attempt to comply with its recommendations.

PMID- 12803224
TI  - Overlooked down under.

PMID- 12803225
TI  - Recognizing Chagas' disease.

PMID- 12803226
TI  - Unmasking a hot dialysis issue.

PMID- 12803227
TI  - Keeping an eye on calcium levels.

PMID- 12803228
TI  - Completing advance directives for health care decisions: getting to yes.
AB  - The concept of advance directives for health care decision making has been
      judicially condoned, legislatively promoted, and systematically implemented by
      health care institutions, yet the execution rate of advance directives remains
      low. Physicians should discuss with their patients advance care planning
      generally and end-of-life issues specifically, preferably when patients are in
      good health and not when they face an acute medical crisis. The physician
      hospital relationship poses particular challenges for the optimal implementation
      of advance directives that must be addressed. Hospital administrators must
      improve education of patients and physicians on the value of such documents as
      well as internal mechanisms to ensure better implementation of directives. Health
      insurance plans may be better able to ensure optimal gathering and implementation
      of directives. Patients must become more familiar and more comfortable with
      advance care planning and the reality of death and dying issues. Full acceptance
      of the value of directives ultimately rests on achieving full participation of
      all involved--providers, patients, families, and payors--in this most profound
      process.

PMID- 12803229
TI  - Maggot debridement therapy: a living cure.

PMID- 12803230
TI  - End-of-life algorithms.
AB  - Tools and strategies for eliciting patient preferences for end-of-life care are
      often absent, of poor quality, or ignored. The American Medical Association's
      Council on Ethical and Judicial Affairs has proposed new guidelines for the
      "optimal use" of advance directives. The guidelines urge the use of detailed work
      sheets in "tailoring end-of-life care to patients' preferences" and suggest a
      process to be followed by physicians in educating patients about death and dying.
      However, these well-intentioned guidelines face 3 key obstacles: the negative
      consequences of "ritualizing" end-of-life planning, physicians' inclination to
      disdain and to delegate to others communication about end-of-life preferences,
      and the tardiness of medical pedagogy in emphasizing end-of-life care and
      communication as crucial for the success of future physicians.

PMID- 12803231
TI  - Multimodal distribution versus logarithmic transformation of thyroid volumes in
      adolescents: detection of subgroup with subclinical thyroid disorders and its
      impact on the assessment of the upper limit of normal thyroid volumes.
AB  - Our objective was to evaluate whether there is a multimodal distribution of
      thyroid volume (ThV) in iodine-replete adolescents and to examine the relation
      between excessive ThV and the presence of thyroid hypoechogenicity (HE), serum
      thyroperoxidase antibodies (anti-TPO) and TSH levels >4.5 mU/l. ThV was measured
      by ultrasound in adolescents aged 13 yr (N = 1083) and 17 yr (N = 1089) from 22
      schools in 6 districts of eastern Slovakia and expressed as ml and ml/m2 body
      surface area. For each age group the multimodal distribution of ThV values was
      tested by computing their frequency at intervals of 0.5 m/m2 and plotting the
      cumulative frequency on a probability scale in which each segment with normal
      distribution should give a straight line. In all examined subjects the HE was
      evaluated by ultrasound; in 924 (42.5%) of those anti-TPO was estimated by
      radioimmunoassay and TSH by immuno-electrochemiluminiscent assay. The medians of
      urinary iodine found in 55-164 spot urine samples from each of 6 districts (total
      number = 1003) were 126-142 microg/l, indicating an iodine-replete status. There
      was a trimodal distribution of ThV in each group, 80-85% in the lowest, 10-15% in
      the middle, and 5-7% in the upper segments. In the 10th ThV decile of the 17-yr
      group the frequency of HE (33/109 = 30.3%), anti-TPO (13/62 = 21.0%) and TSH
      (6/62 = 9.7%) was significantly higher than that in the 1st-9th decile (71/980 =
      7.2%, P<0.001; 23/482 = 4.8%, P<0.001 and 5/482 = 1.0%, P<0.001, resp.). Similar
      differences were found in the 13-yr group (21/109 = 19.2% vs. 58/974 = 5.9%,
      P<0.001 for HE, 5/60 = 8.3% vs. 3/320 = 0.9%, P<0.001 for anti-TPO and 2/64 =
      3.1% vs. 4/317 = 1.3% (not significant) for TSH >4.5 mU/l. Thus in the 10% of
      subjects with the highest ThV, the frequency of HE and anti-TPO was 4-5 times
      higher than in the remaining 90%. Our data indicate that an epidemiological
      evaluation of a large population of adolescents can detect a group with early
      signs of thyroid dysfunction (e.g. excessive ThV, increased frequency of HE, anti
      TPO and TSH >4.5% mU/l), although such dysfunction may not be clinically
      apparent. This contrasts with numerous earlier reports which used a logarithmic
      transformation of the data in similar ThV sets, thus making the data appear
      homogeneous (unimodal) and with a normal distribution and obscuring the true
      multimodal distribution. This further prevents recognition of subjects with
      evidence of disordered thyroid status which thus become falsely included into a
      normal range.

PMID- 12803232
TI  - Factors affecting bone mineral density in hemodialysis patients with diabetic
      nephropathy.
AB  - BACKGROUND: It remains undetermined whether bone mineral density (BMD) of
      hemodialysis (HD) patients with diabetes mellitus (DM) is reduced or not. The
      present study was performed to compare BMD between HD patients with DM and
      chronic glomerulonephritis (CGN). We analyzed the factors which affected BMD of
      139 patients with chronic HD enrolled in this cross-sectional study. METHODS: BMD
      of forearm [1/3-radius (R) and ultradistal (UD)-R] were measured by dual-energy x
      ray absorptiometry. RESULTS: 1/3R-BMD and UDR-BMD of DM patients were comparable
      to those of CGN patients. In DM patients, body mass index (BMI) was positively
      correlated with UDR-BMD, serum levels of PTH and creatinine were negatively
      correlated with 1/3R-BMD, and serum level of beta2-microglobulin (betaMG) was
      positively correlated with UDR-BMD. In CGN patients, duration of HD and height
      were negatively correlated with 1/3R- and UDR-BMD, serum levels of uric acid and
      triglyceride were positively correlated with 1/3R- and UDR-BMD, and serum level
      of total cholesterol was positively correlated with UDR-BMD. In stepwise
      regression analysis, BMI and serum levels of creatinine and betaMG were selected
      for UDR-BMD in DM patients, although serum PTH level was selected for 1/3R-BMD.
      CONCLUSION: BMD at forearm was comparable between DM and CGN in HD patients. The
      factors affecting BMD seemed to be different between DM and CGN.

PMID- 12803233
TI  - Octreotide-sensitive ectopic ACTH production by islet cell carcinoma with
      multiple liver metastases.
AB  - We report a 21-year-old woman with ectopic ACTH syndrome due to islet cell
      carcinoma with multiple liver metastases. On admission, she showed Cushingoid
      appearance (moon face, central obesity etc.) and had acute respiratory distress
      syndrome due to pneumocystis carinii pneumonia. Laboratory examination revealed
      marked elevations of plasma ACTH (735 pg/ml) and cortisol (145 microg/dl) with a
      profound hypokalemia (2.0 mEq/l). She was found to have multiple masses in the
      liver and a solid mass in the tail of pancreas by abdominal computerized
      tomography scanning. Treatment with octreotide successfully reduced elevated
      plasma ACTH and cortisol levels, and she received frequent transhepatic arterial
      embolization and chemotherapy. The primary pancreatic tumor was surgically
      removed, revealing islet cell carcinoma which contained high content of ACTH (100
      microg/g wet weight) and abundantly expressed proopiomelanocortin and
      somatostatin receptor subtype-2 mRNAs as determined by Northern blot analysis.
      Postoperatively, she was free from symptoms for almost one year. However,
      progressive enlargement of multiple liver metastases refractory to chemotherapy
      led her to decide on total hepatectomy and liver transplantation from her father.
      After liver transplantation, she remained almost free from symptoms for almost
      one year. However, metastases developed to the mediastinal and paraaortic lymph
      nodes as detected by 111[In] pentetreotide scintigraphy. Eleven months after
      liver transplantation, she was again treated with octreotide and, 16 months
      after, with metyrapone, both of which were effective in reducing ACTH and
      cortisol levels, respectively, until she died of acute respiratory failure. This
      case of a young female patient with ectopic ACTH-producing islet cell carcinoma
      of the pancreas was quite unique in that she survived for 5 years despite the
      acute onset and rapid progression of the multiple liver metastases at least in
      part due to the long-lasting favorable response to octreotide and living-related
      liver transplantation.

PMID- 12803234
TI  - Role of Na+ and Ca2+ channels in the preoptic LH surge generating mechanism in
      proestrous rats.
AB  - We studied whether Na+ and Ca2+ channels are involved in the neural mechanism
      responsible for the surge of gonadotropin-releasing hormone (GnRH) in proestrous
      rats. In experiment 1, female rats in proestrus were i.p. injected at 1345 h with
      pentobarbital sodium (35 mg/kg) to block spontaneous surge of LH and electrical
      stimulation was applied between 1400 and 1600 h to the preoptic area (POA)
      together with POA injection of 0.5 microl saline containing the Na+ channel
      blocker tetrodotoxin (TTX) at a concentration of 1 microM, 2 microM, or 5 microM.
      Since 5 microM TTX completely blocked the increase in serum LH concentrations
      evoked by the POA stimulation, we used this concentration in experiment 2 to
      observe the TTX effect on the spontaneous LH surge. In experiment 2, bilateral
      injections of 1.5 microl of 5 microM TTX at 1430 h in the POA in proestrous rats
      postponed the peak time and reduced the peak level of the LH surge. In experiment
      3, bilateral injections of 1.5 microl of 5 microM L-type Ca2+ channel blocker
      nifedipine at 1430 h in the POA completely blocked the LH surge. Since the cell
      bodies of GnRH neurons are primarily concentrated in the POA in rats, these
      results suggest that both voltage-sensitive Na+ channels and Ca2+ channels
      contribute to the generation of action potentials at GnRH cell bodies for the
      surge release of GnRH.

PMID- 12803235
TI  - Cushing's syndrome due to bilateral adrenocortical adenomas with unique
      histological features.
AB  - Cushing's syndrome due to bilateral cortisol-secreting adenomas rarely occurs. We
      present a case of Cushing's syndrome due to bilateral adenomas. Both adenomas had
      distinct cell compositions, and were compared with emphasis on
      immunohistochemical and enzyme histochemical analysis for cytochrome P450(11beta)
      and 3beta-hydroxysteroid dehydrogenase (3betaHSD). A 37 year-old female was
      diagnosed with ACTH-independent Cushing's syndrome based on physical findings and
      hormonal evaluation. High-resolution CT scan showed bilateral adrenocortical
      adenomas and atrophied glands. 131I-methylnorcholesterol incorporation into both
      glands suggested both adenomas were functional. Clinical diagnosis prior to
      surgery was ACTH-independent Cushing's syndrome due to functioning bilateral
      adenomas. The left adrenal gland was totally resected, while the right one was
      partially resected by laparoscopic approach. Both adenomas were black on cut
      sections, and were comparatively evaluated by immunohistochemical and enzyme
      histochemical analysis for P450(11beta) and 3betaSD. The left adenoma was 1.6 cm
      in diameter and had a complex cellular composition and enzyme expression similar
      to that of primary pigmented nodular adrenocortical disease (PPNAD), while the
      right adenoma was 1.8 cm in diameter with compact cells typical of a solitary
      cortisol-producing adenoma. Adjacent bilateral adrenal cortex showed marked
      atrophy, but contained several micronodules. Serum cortisol levels, both at basal
      and after a low dodexamethasone, normalized thirteen months after surgery. In
      conclusion, the present case of Cushing's syndrome with bilateral adrenal
      adenomas demonstrated for the first time the simultaneous occurrence of two
      distinct adenomas, an ordinary cortisol-producing adenoma and a PPNAD-like
      adenoma. Further case reports of multiple adrenal adenomas should be well
      analyzed to clarify whether the results from this case represent a new subgroup
      of ACTH-independent Cushing's syndrome.

PMID- 12803236
TI  - Mortality in 154 surgically treated patients with acromegaly--a 10-year follow-up
      survey.
AB  - To determine the effects of surgery and adjuvant therapy on the mortality rate of
      Japanese patients with acromegaly, 154 surgically treated patients were followed
      until death or December 2000. Mean follow-up period was 10.0 +/- 6.5 (SD) years.
      Postoperative GH levels, mean values of GH levels measured in the first
      postoperative month, were <2.5 ng/mL in 73 (47.4%), 2.5-5.0 ng/mL in 50 (32.5%),
      and >5.0 ng/mL in 31 patients (20.1%). Three of 123 patients with postoperative
      GH levels <5.0 ng/mL underwent a second transsphenoidal surgery (TSS), the other
      120 received no further treatment. Additional treatments, including second TSS,
      medical treatment, and gamma-knife irradiation for residual tumor, were
      administered to 25 of 31 patients whose postoperative GH was >5.0 ng/mL. Among
      the total 154 patients surveyed, 11 (7.1%) died during the follow-up period. The
      standard mortality ratio (SMR) was 1.17, not different from age- and sex-matched
      controls. The SMR of the 72 patients with postoperative GH <2.5 ng/mL was better
      than that of the 51 patients whose postoperative GH was 2.5-5.0 ng/mL (1.09 vs.
      1.64); however, the difference was not statistically significant. In conclusion,
      TSS and adequate adjuvant treatment decreased the excess mortality rate of
      acromegalics to nearly the same level as that of the general Japanese population.

PMID- 12803237
TI  - HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm.
AB  - It is generally known that even with permanent sections, the differential
      diagnosis between follicular adenoma and follicular carcinoma is often difficult
      to determine. It is not unusual to encounter patients diagnosed with benign
      follicular adenoma whose diagnoses have to be changed to malignancies because of
      recurrence or metastasis. As the monoclonal antibody HBME-1 produced by
      mesothelioma cells has been shown to have reactivity in thyroid carcinomas, we
      investigated the diagnostic usefulness of HBME-1 in follicular neoplasms.
      Immunohistochemical staining for HBME-1 was performed on 205 various thyroid
      tumors using the labeled streptavadin biotin peroxidase method. When hematoxylin
      eosin (HE) staining was performed again for this study and all cases were
      examined in accordance with the WHO Histological Classifications 2nd Edition,
      87.2% (54/62) of adenomatous goiter and 72.6% (45/62) of follicular adenoma were
      negative. On the other hand, 84.6% (33/39) of follicular carcinoma and 97.2%
      (35/36) of papillary carcinoma were positive. All anaplastic (2/2) and medullary
      (4/4) carcinoma were negative. Examination in follicular neoplasms had a
      sensitivity of 84.6%, specificity of 72.6%, positive predictive value of 66.0%
      and overall accuracy of 77.2%. Among the cases treated as follicular adenoma
      clinically, the diagnosis of 13 cases was changed to follicular carcinoma, and 6
      cases to papillary carcinoma for this study. These cases showed strong HBME-1
      positivity. Two of the follicular carcinoma cases experienced recurrence. We
      conclude that immunohistochemical staining with HBME-1 may be useful clinically
      to pick out cases with a high risk of recurrence in follicular carcinoma, and
      that benign adenoma cases need close follow-up.

PMID- 12803238
TI  - Virilizing adrenocortical adenoma with Cushing's syndrome, thyroid papillary
      carcinoma and hypergastrinemia in a middle-aged woman.
AB  - We report a rare case of virilizing adrenocortical adenoma complicated with
      Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia. A 45-year
      old woman had a history of amenorrhea for 10 years, hypertension for 8 years, and
      diabetes mellitus for 3 years. Physical examination showed a masculinized woman
      with severe hirsutism, male-like baldness, deep voice, acne in the precordia, and
      clitorism. Plasma testosterone, DHEA-S and urinary 17-KS were high, and plasma
      cortisol level was it at the upper limit of the normal range, but it did not show
      a diurnal rhythm nor was suppressed by 2 and 8 mg of dexamethasone. Abdominal CT
      scan showed a left adrenal tumor (4.5 cm in size). Adrenal scintigram revealed
      uptake of the tracer on the left side, and plasma cortisol concentration was high
      in a blood sample from the left adrenal vein. Left adrenalectomy was performed.
      Histopathological features of resected adrenal tumor were consistent with those
      of adrenocortical adenoma, consisting of tumor cells with eosinophilic compact
      cytoplasm. Immunohistochemical staining for steroidogenic enzymes showed
      reactivity for P450sec, 3 beta-HSD, P450c17, P450c21 and P450c11. Plasma
      testosterone and cortisol levels decreased to the normal range postoperatively.
      The patient was also found to have a papillary thyroid carcinoma and
      hypergastrinemia. Our patient is a rare case of virilizing adrenocortical adenoma
      associated with Cushing's syndrome, thyroid papillary carcinoma, and
      hypergastrinemia.

PMID- 12803239
TI  - Physiologic role of decidual beta1 integrin and focal adhesion kinase in
      embryonic implantation.
AB  - Implantation refers to a series of interactions between embryo and endometrium
      including hatching, attachment, and outgrowth. We investigated the expression and
      function of beta1 integrin and focal adhesion kinase (FAK) in human decidual
      cells during implantation. Immunofluorescent staining localized beta1 integrin to
      surfaces of cultured decidual cells. Double staining for beta1 integrin and
      mediators of intracellular signaling involving beta1 integrin, such as FAK and
      vinculin, colocalized beta1 integrin with these substances, suggesting that human
      decidual cells express beta1 integrin in the focal adhesion region. We next
      investigated the actions of beta1 integrin and FAK in implantation by co
      culturing mouse embryos and human decidual cells. Mouse blastocysts attached to
      cultured decidual cells after embryo hatching, usually within 24 h of culture
      initiation. Blastocysts attached to decidual cells exhibited extensive outgrowth
      at 48 h. Treatment of decidual cells with an antibody against beta1 integrin or
      with an antisense FAK oligonucleotide did not affect hatching or attachment of
      blastocysts, but either one could inhibit outgrowth. Thus, it was concluded that
      human decidual beta1 integrin and FAK participate in this final step of
      implantation.

PMID- 12803240
TI  - Expression of Fas/Fas-ligand, Bcl-2 protein and apoptosis in extravillous
      trophoblast along invasion to the decidua in human term placenta.
AB  - There are two local subtypes of extravillous trophoblast (EVT): one is the
      proliferative phenotype of EVT, which primarily consists of proximal cells and
      the other is the invasive phenotype of EVT, which is composed mainly of distal
      cells of cell columns. The mechanism of invasion of EVT to the decidua remains
      obscure. In order to elucidate the potential role of apoptosis along the invasion
      of EVT to the decidua, we have assessed the expression of apoptosis-regulating
      proteins including Fas antigen (Fas), Fas-ligand (Fas-L) and Bcl-2 protein, and
      apoptosis in the proliferative phenotype of EVT and the invasive phenotype of EVT
      in term (37 to 38 wk) placenta Fas, Fas-L and Bcl-2 protein expression were
      examined by avidin/biotin immunoperoxidase method. Apoptosis was assessed by in
      situ DNA 3'-end labeling method. Appearance of apoptotic nuclei in EVT was also
      examined by transmission electron microscopy. Mean percentage of apoptosis
      positive nuclei in the invasive phenotype of EVT was significantly higher than
      that in the proliferative phenotype of EVT. Transmission electron microscopy
      revealed the presence of apoptotic nuclei in the invasive phenotype of EVT.
      Immunohistochemical analyses revealed that Fas and Fas-L expression in the
      invasive phenotype of EVT were more abundant than those in the proliferative
      phenotype of EVT, while Bcl-2 protein expression in the invasive phenotype of EVT
      was less abundant than that in the proliferative phenotype of EVT. The present
      findings suggest that Fas/Fas-L and Bcl-2 protein expression participate in the
      regulation of apoptosis in EVT along the invasion to the decidua, and that the
      increased occurrence of apoptosis in the invasive phenotype of EVT may be
      attributable to the increased expressions of Fas and Fas-L and decreased
      expression of Bcl-2 protein in those cells in term placentas.

PMID- 12803241
TI  - The higher immunoreactivity to ACE (angiotensin converting enzyme) in patients
      with type 2 diabetes mellitus than in non-diabetic individuals.
AB  - In a random sample of 200 patients with type 2 diabetes mellitus,
      immunoreactivities to ACE (angiotensin converting enzyme) were measured by ELISA.
      Immunoreactivities were positive for 129 (64.5%) patients, and were positive in
      30 (83.3%) out of 36 patients in the early stage of clinical diabetic
      nephropathy. Serum ACE activity in rabbits immunized with ACE decreased to 50% of
      the control level after 7 months (78.0 +/- 3.8 IU/L/37 degrees C, basal, 42.0 +/-
      5.0 at 7 months and 33.3 +/- 3.5 IU/L/37 degrees C at 8 months, respectively).
      When rabbit serum containing antiACE antibodies was mixed, after heat-treatment
      at 56 degrees C for 30 min, with normal human serum, the ACE activity was reduced
      in a concentration-dependent manner. These results suggested that anti-ACE
      autoantibody may be present in patients with type 2 diabetes mellitus. However,
      the absence of data on the epitope for the antibody does not allow any conclusion
      except that the immunoreactivities to ACE are higher in type 2 diabetic patients
      than in non-diabetic individuals.

PMID- 12803242
TI  - Functional giant parathyroid cyst with high concentration of CA19-9 in cystic
      fluid.
AB  - A 63-year-old man was admitted to our hospital for the evaluation of
      hypercalcemia and anterior neck mass. Laboratory findings revealed hypercalcemia,
      hypophosphatemia, and hypercalciuria, as well as elevated serum levels of
      parathyroid hormone (PTH) and alkaline phosphatase. Computerized tomography and
      magnetic resonance images showed that the mass contained a cystic area.
      Parathyroid scintigraphy using either 99mTc-sestamibi alone or 201Tl-chloride in
      conjunction with 99mTc-pertechnetate for thyroid image subtraction showed uptake
      of the radioactivity into the cyst wall, suggesting that the mass originated from
      the parathyroid. Fine needle aspiration biopsy revealed that the cyst fluid was
      serous and bloody with extremely high concentrations of both PTH and CA19-9. The
      patient was diagnosed as primary hyperparathyroidism caused by parathyroid cyst
      and cervical exploration was performed. The cyst was dissected away along with
      the right lobe of the thyroid gland. After tumor removal, serum calcium and PTH
      levels were normalized. Histological study showed that the tumor possessed
      malignant potential with capsular invasion as well as moderate cellular atypia
      with trabecular pattern in arrangement. Parathyroid cells in the wall of the
      cystic tumor were immunostained positively for CA19-9, suggesting that CA19-9 in
      the cyst fluid was produced from the cells.

PMID- 12803244
TI  - A case of fulminant type 1 diabetes with transiently positive anti-GAD
      antibodies.
AB  - A subtype of idiopathic type 1 diabetes with a rapid onset and no diabetes
      related antibodies has been recently advocated as non-autoimmune fulminant type 1
      diabetes. However, it is not definite yet that this subtype is always caused by
      non-autoimmune mechanism. A 48-year-old man was admitted to our hospital because
      of high plasma glucose and renal insufficiency. Laboratory findings were as
      follows: plasma glucose 1052 mg/dL, urinary ketone bodies (+/-), arterial blood
      pH 7.44, bicarbonate 23.8 mmol/L, base excess 0.3 mmol/L, plasma osmolality 342
      mOsm/L, serum creatinine 2.1 mg/dL, blood urea nitrogen 69.7 mg/dL, and serum
      creatine kinase 1024 IU/L, giving a diagnosis of acute renal failure secondary to
      rhabdomyolysis associated with diabetes. Urinary C-peptide reactivity was 4.7
      microg/day. The level of HbAlc was 7.0%, not so high as compared to that of
      plasma glucose, indicating an aggravation of diabetes within the recent short
      period. Antibodies to islet cell antigen, IA-2 and insulin were negative, while
      those to glutamic acid decarboxylase (GAD) were positive at 13.1 U/mL, which were
      negative half a year and two years and a half later. Serum amylase level was
      within normal range at admission, increased to 380 IU/L and normalized in 4 to 5
      weeks as serum creatinine lowered. These data are compatible to the diagnosis of
      fulminant type 1 diabetes. However, the present case is different from others in
      positive antibodies to GAD at admission that turned to be negative subsequently.
      Considering our results and others together, further investigations are necessary
      to clarify whether all cases of fulminant type 1 diabetes are non-autoimmune or
      some of them are caused by autoimmune mechanism.

PMID- 12803243
TI  - Rhabdomyolysis in a patient with hypothyroidism.
AB  - We describe a case of rhabdomyolysis associating hypothyroidism. Hypothyroidism
      frequently leads to myalgias, muscle stiffness, cramps and sometimes elevated
      levels of muscle enzymes, but rhabdomyolysis is quite rare. This report describes
      a case of rhabdomyolysis associating hypothyroidism in a 19-year old man. Muscle
      enzyme levels were typical of rhabdomyolysis. Muscle biopsy and electromyographic
      findings were compatible with hypothyroid myopathy. Muscle functions completely
      recovered with levothyroxine therapy. The present case represents rhabdomyolysis
      secondary to undiagnosed hypothyroidism in a developed stage which manifests
      itself with rhabdomyolysis.

PMID- 12803246
TI  - Sequencing batch biofilter operation for treatment of methyl ethyl ketone (MEK)
      contaminated air.
AB  - Biofiltration is increasingly used as a method for decontaminating gas streams
      containing low concentrations of biodegradable volatile organic compounds. In
      typical biofilter installation control is quite passive and is often restricted
      to adjustment of the medium's moisture content or nutrient supply. Although
      inexpensive, such operation limits implementation of engineering decisions that
      could improve performance during normal operation orallow effective handling of
      the short-term variations in the waste stream typical of industrial operations.
      This paper describes how sequencing batch operation can be applied to biofilters
      designed and operated as controlled, unsteady-state, periodic processes for the
      destruction of gas-phase contaminants. In the studies described herein, the
      impact of sequencing batch operation was assessed in a methylethyl ketone
      degrading biofilter over a 130-day period. The biofilter was packed with a
      polyurethane foam medium that contained activated carbon. Methyl ethyl ketone and
      carbon dioxide concentrations were monitored during both normal steady loading
      conditions and short-term, unsteady-state transient loading conditions (i.e.,
      shock loading). A gas stream containing 106 ppm, methyl ethyl ketone was used for
      normal loading studies, and several model shock loads consisting of 530 ppm,
      methyl ethyl ketone for a duration of one hour were used to assess system
      response to transient loads. Data are presented which clearly demonstrate that
      sequencing batch operation can be successfully applied to biofilters treating
      methyl ethyl ketone contaminated air streams. Such operation can increase an
      operator's ability to minimize contaminant emission during transient periods of
      elevated contaminant loading.

PMID- 12803245
TI  - Relationship between exercise training-induced increase in insulin sensitivity
      and adiponectinemia in healthy men.
AB  - Circulating concentrations of adiponectin, an adipocyte-derived protein, are
      increased by thiazolidinediones and by weight reduction, accompanied with
      improvement in insulin sensitivity. The effect of exercise training, another
      therapy to increase insulin sensitivity (SI), on adiponectinemia is currently
      unclear. The present study was undertaken to clarify whether exercise training
      induced increase in SI is related to changes in adiponectinemia in healthy men.
      Twelve healthy non-obese men underwent ergometer training at lactate threshold
      (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified
      intravenous glucose tolerance test was performed before and at 16 h and 1 week
      after the last training session to determine SI using a minimal-model approach.
      Serum levels of adiponectin were determined at the same time. After the exercise
      training, VO2max and LT were significantly increased by 7.2% and 22.3% (P<0.01),
      while BMI and body fat mass remained unchanged. SI was significantly increased at
      16 h after the last training session (from 7.0 +/- 3.1 to 9.6 +/- 3.6 [x 10(-4) x
      (microU/ml)(-1) x min(-1)], P<0.01), but returned toward the basal levels at 1
      week after the cessation of the training. Serum adiponectin concentrations before
      the training (20.9 +/- 7.4 microg/ml) were positively correlated with SI. The
      concentrations were slightly but significantly decreased at 16 h (17.2 +/- 6.6
      microg/ml, P<0.05), and returned to the basal values at 1 week after the
      training. From these results, it can be concluded that exercise training-induced
      increase in SI is not dependent on the increase in adiponectinemia in healthy
      men.

PMID- 12803247
TI  - Acid neutralisation capacity of accelerated carbonated stainless steel slag.
AB  - The acid neutralisation capacity test is widely used to assess the long-term
      performance of waste materials prior to disposal. Samples of fixed mass are
      exposed to increasing additions of nitric add in sealed containers and the
      resultant pH is plotted as a titration curve. In this work, the add
      neutralisation capacity test was used in the assessment of an accelerated
      carbonated stainless steel slag. Difficulties arose in applying the test
      procedure to this material. This was largely because of the raised pressure from
      significant volumes of released carbon dioxide trapped in the sealed sample
      containers, causing an alteration to leachate pH values. Consequently, the add
      neutralisation capacity test was modified to enable testing of samples in
      equilibrium with the atmosphere. No adverse effects on the results from testing
      of a carbonate free material were recorded.

PMID- 12803248
TI  - Impact of landfill leachate on anaerobic digestion of sewage sludge.
AB  - The feasibility of mesophilic anaerobic co-digestion of landfill leachate and
      sewage sludge was examined in a bench-scale experiment. Three complete-mix, flow
      through digesters were operated in a semi-continuous mode. During both phases of
      research all digesters received 500 ml d(-1) of raw sludge and Reactor 1 was
      always the control reactor--fed sludge only. During Phase 1, leachate volumes
      less than 12% of the sludge volume were fed to Reactors 2 and 3. During Phase 2
      larger amounts of leachate were added, exceeding 20% of sludge volume which led
      to an overall decrease in the hydraulic residence time of the digesters. All
      reactors achieved stable operation, which indicated that the co-digestion of
      sewage sludge and landfill leachate is feasible During Phase 1, an increase in
      the average daily methane production from 2.5 l d(-1) to 3.1 l d(-1) and 3.2 l d(
      1) was observed; the biomethanation production (BMP) increased from 0.46 to 0.6
      m3 - 0.7 m3 CH4 (kg VS rem.)(-1). The average volatile solids reduction (VSR)
      increased from 46.1% to 48.6% and 49.0%. In Phase 2, the total methane production
      in the control reactor was significantly higher, at 4.6 l d(-1), while the
      addition of larger, by volume, amounts of leachate, decreased the methane
      production to 4.3 l d(-1) and 4.2 l d(-1), respectively. The average BMP values
      were 0.8, 0.87, and 0.81 m3 CH4 (kg VS rem.)(-1), respectively. In Phase 2,
      leachate addition decreased the average VSR from 51% to 49% and 45.6%. After
      calculating that leachate addition to digesters would not increase heavy metal
      concentrations in the produced biosolids it was concluded that mesophilic
      anaerobic co-digestion of sewage sludge and landfill leachate is feasible, and
      provides a promising alternative to aerobic co-treatment.

PMID- 12803249
TI  - Evaluation of a single-residence biological wastewater treatment system with
      thermal biosolids destruction.
AB  - An aerobic package residential wastewater treatment system was evaluated to
      determine process performance while connected to a single-family residence. Three
      components of the study were: 1) long-term (5-month) performance, 2) 24-hour
      performance track studies, and 3) enhanced loading study. For the long-term
      performance and enhanced loading study hourly influent and effluent samples were
      collected and composited on a flow-averaged basis. Short-term fluctuations in
      flow and mass loading rates were evaluated from the hourly discrete samples. The
      long-term average removals for CBOD5, TSS, and inorganic N were 97.3, 97.8
      percent, and 89.6 percent, respectively, with average effluent concentrations of
      5.7, 5.9, and 2.2 mg l(-1). To prevent biosolids buildup in the system and to
      eliminate the need for frequent sludge removal a thermal process is incorporated
      into the system for biosolid ash conversion. Periodic spikes of influent mass
      loading rates persisted in the treatment system at time scales of one hour or
      less. Treatment process peformance, evaluated from 24-hour composite samples, was
      not affected by the highly variable infuent concentrations and flow rates
      experienced in the study single-family household. Average monthly power
      consumption for aeration, thermal processing of accumulated biosolids, and
      biomass re-circulation was 132 kWh per month, or about 4.4 kWh per day.

PMID- 12803250
TI  - Effects of trace element addition on volatile fatty acid conversions in anaerobic
      granular sludge reactors.
AB  - The effect of the addition of trace elements on the conversion of a mixture of
      volatile fatty adds (Acetate, Propionate, Butyrate, in a ratio 3:1:1) by
      anaerobic granular sludge was investiated. Two Upflow Anaerobic Sludge Bed
      reactors (pH 7, ranging 30 degrees C) were operated for 140 days at an organic
      loading rate from 2 g COD l(-1) d(-1) up to 10 g COD l(-1) d(-1) and a hydraulic
      retention time of 12 hours. One reactor (R1) was supplied with a trace metal
      cocktail in the basal medium, whereas trace metals were omitted from the influent
      of the second reactor (R2). As a result, the trace metal concentration in the
      granules from R2 steadily decreased at a rate of 48 microg metal g(-1) TS d(-1)
      down to 35% of their initial value. In contrast, trace metals accumulated in
      granules present in R1. At the end of the experiment, the COD removal
      efficiencies were 99 and 77% for, respectively, the control (R1) and deprived
      (R2) reactors. This difference was due to lack of propionate conversion by sludge
      from R2. No difference in the acetate and butyrate conversion capacity of both
      reactors was observed. The conversion of acetate, propionate and methanol were
      stimulated by the continuous addition of metals to the influent, a sludge of R1
      had higher maximum specific activity values compared to sludge of R2. However,
      both sludges had a similar maximum specific activity with butyrate. Surprisingly,
      maximum specific activity tests using individual trace metals showed that the
      addition of a particular trace element in the activity test medium did not affect
      the degradation rates of aspecific substrate, i.e. acetate, propionate, butyrate
      and methanol.

PMID- 12803251
TI  - Environmental assessment of cement/foundry sludge products.
AB  - This work deals with the environmental assessment of products based on cement and
      a waste from a cast iron activity. The waste is a foundry sludge from wastewater
      treatment previously characterized. This industrial waste shows a high water
      content (62.4%) and a hazardous behavior due to its metallic content mainly Zn
      (16.5%), together with a low fraction of organic pollutants, mainly phenolic
      compounds. The feasibility of immobilizing both typs of contaminants was studied
      using Portland cement as binder at different cement/waste ratios. The parameters
      of environmental control were the ecotoxicity and mobilization of zinc and
      phenolic compounds, all determined on the basis of compliance leaching tests. The
      acid neutralization capacity of the cement/waste products was measured in order
      to obtain information on their buffering capacity. Experimental results from
      chemical analysis of leachates led to a non ecotoxic character of cement/waste
      products Although the metallic ions were mobilized within the cement mattices,
      the organic matter did not allow the formation of monolithic forms and an
      efficient immobilization of phenolic compounds. Concerning the acid
      neutralization capacity, this parameter was shown to depend mainly on the
      quantity of cement, although a decrease in alkalinity was observed when the
      amount of water in the cement/waste products increased.

PMID- 12803252
TI  - Determination of organic matter in grinding sludges by UV spectrophotometry.
AB  - The aim of this paper is to determinate the total organic matter content of
      grinding sludges by a simple and fast methodology based on a solvent extraction
      followed by a UV spectrophotometry analysis. Several UV spectra exploitation
      methods are used. The multiwavelength deconvolution procedure provides
      quantitative results in good accordance with those obtained by a gravimetric
      method, possibly underestimated and enables a separate quantification of the
      cuttings fluids and the lubricants in the sludges. The normalisation procedure
      and the search of isobestic points provide important qualitative information on
      the evolution and on the composition of the oils used in metal processing.
      Therefore, this study is a first step for the development of a tool for the
      characterisation of organic matter in grinding sludges.

PMID- 12803253
TI  - Determination of the hydraulic residence time in a trickling biofilter filled
      with organic matter.
AB  - Biofiltration process using peat as media has been shown to be efficient for the
      treatment of agroindustrial, chemical and municipal effluents. However,
      determining the hydraulic retention time of this process is difficult due to many
      factors. Generally tracer techniques are used, but they measure the molecular
      retention time instead of the hydraulic retention time; and depending on the
      case, the results can be wrong. In order to contribute to solving this problem,
      the objective of this research was to find a trustworthy and adequate technique
      to determine the hydraulic retention time for a process using a very adsorbent
      filter bed material (peat). An overview of the hydraulic behaviour of a peat bed
      filter related to their particular structural composition is presented. Then,
      based on these characteristics, two different techniques to determine the
      hydraulic retention time were developed and tested. The first, an indirect
      modified tracing technique and, the second, a direct one which determines the
      volume of liquid in treatment into the filter bed through the establishment of a
      relation between the volume of porosity and the volume of empty spaces (or not
      occupied by liquid) into the filter bed. The results obtained showed that the
      proposed techniques gave similar results and proved adequate.

PMID- 12803254
TI  - Removal of heavy metals from waste waters by vermiculites.
AB  - The sorbent behaviour of (natural and exfoliated) vermiculite minerals was
      studied with respect to metal cations (Ni, Cu, Cd) commonly present in waste
      waters of the metal finishing industry. The Langmuir model was found to describe
      the sorption processes well, showing the maximum sorption capacities of natural
      vermiculite to be high enough (bCd = 26.0 mg g(-1); performed bCd = 23.5 mg g(
      1); bNi = 19.3 mg g(-1)) for its use in metal waste water purification systems to
      be feasible. The column studies performed with this mineral show that a large
      volume of metal solutions with similar concentrations to those usually present in
      waste waters can be purified down to the legal limit of waste. These positive
      results are ratified when real waste waters are used at lab-scale as well as at
      semi-industrial scale, validating the use of this mineral as a cost-effective
      treatment to purify such waste waters.

PMID- 12803255
TI  - Factors affecting washout in intermittently feed upflow anaerobic reactors:
      experimental tests and modelling.
AB  - This paper reports the results of experimental investigations carried out on a
      full-scale ABR and on a pilot UASB to determine biomass washout for various
      intermittent feed conditions. Particularly, the tests aimed to determine the
      extent to which sludge washout is affected by such factors as: daily flow
      distribution; upflow velocity; concentration and sedimentation properties of the
      biomass. Moreover, in order to obtain a tool to estimate sludge washout in
      different influent flow conditions, a simulation model of the sludge transport
      phenomena in the uplow anaerobic reactors is proposed. The results showed that
      when the influent flow is interrupted for long periods (above 1 hour), once it is
      resumed considerable losses of biomass into the effluent were found, independent
      of the upflow velocity. In contrast with shorter periods, regular sludge
      expansion took place even with very high upflow velocities (up to 4 m h(-1)),
      giving rise to limited sludge washout and high removal efficiencies.

PMID- 12803256
TI  - Heavy metal stabilization by means of innovative alumino-silicate matrix.
AB  - Powdered tuff mixed with NaOH solution has been hydrothermally cured at
      temperatures ranging from 90 to 150 degrees C. Hardening takes place due to the
      formation of an amorphous binding phase. At the lowest temperature tested a non
      autoclaved process can be carried out. Values of unconfined compressive strength
      were found to vary from 15.5 MPa to 28.9 MPa depending on reaction conditions.
      The matrix was tested as a binder for the stabilization of model systems
      containing cadmium, chromium and lead and for a real system containing a
      secondary lead smelter slag. The stabilization process was tested from both the
      environmental and technological points of view by means of leahcing tests and
      compressive strength measurement. Basic characterization leaching tests carried
      out with the model systems showed that metal release from hardened paste is below
      1%. Compliance leaching test carried out with the real system showed that lead
      release is below the limit set by law. From the technological pont of view, it
      was found that unconfined compressive strength is always higher for the real
      system. Specifically, this system showed compressive strength increasing with
      slag content to values exceeding 86.5 MPa.

PMID- 12803257
TI  - Pyrolysis of composite plastic waste.
AB  - Several different composite plastics were pyrolysed in a fixed bed reactor at
      final temperatures between 350 and 800 degrees C. The composites studied were
      polyester, phenolic, epoxy, vinylester, polypropylene and PET resins, reinforced
      with glass and/or carbon fibre. The product yields of oil gas and solid residue
      were determined together with a detailed composition of the derived gases. There
      was evidence to suggest that calcium carbonate filler, present in the polyester
      and phenolic composites, decomposed to form carbon dioxide at 800 degrees C,
      which was subsequently involved in char gasification reactions. Polyester,
      phenolic and epoxy composites generated highly aromatic, oxygenated condensable
      products. There was no noticeable correlation between the composition of these
      products and the final pyrolysis temperature. The tensile strength of recovered
      glass fibre was lower than that of virgin fibre and decreased markedly as the
      final pyrolysis temperature increased from 650 to 800 degrees C.

PMID- 12803258
TI  - Human immobilization: is the experience in Moscow just the beginning?

PMID- 12803259
TI  - Fluid therapy in sepsis with capillary leakage.
AB  - Sepsis is associated with a profound intravascular fluid deficit due to
      vasodilatation, venous pooling and capillary leakage. Fluid therapy is aimed at
      restoration of intravascular volume status, haemodynamic stability and organ
      perfusion. Circulatory stability following fluid resuscitation is usually
      achieved in the septic patient at the expense of tissue oedema formation that may
      significantly influence vital organ function. The type of fluid therapy,
      crystalloid or colloid, in sepsis with capillary leakage remains an area of
      intensive and controversial discussion. The current understanding of the
      physiology of increased microvascular permeability in health and sepsis is
      incomplete. Furthermore, there is a lack of appropriate clinical study end-points
      for fluid resuscitation. This review considers critically the clinical and
      experimental data analysing the assessment of capillary leakage in sepsis and
      investigating the effects of different fluid types on increased microvascular
      permeability in sepsis.

PMID- 12803260
TI  - Pattern of renal dysfunction associated with myocardial revascularization surgery
      and cardiopulmonary bypass.
AB  - BACKGROUND AND OBJECTIVE: A variable incidence rate of renal dysfunction (3-35%)
      after cardiac surgery with cardiopulmonary bypass has been reported. The aim was
      to define the typical pattern of renal dysfunction that follows coronary surgery
      with cardiopulmonary bypass using albumin, immunoglobulin (IgG), alpha1
      microglobulin and beta-glucosaminidase (beta-NAG) excretion as indicators.
      METHODS: Twenty patients with preoperative normal renal function, defined by
      plasma creatinine, creatinine clearance, fractional excretion of sodium and renal
      excretion of proteins, undergoing elective myocardial revascularization surgery
      with cardiopulmonary bypass, were prospectively studied. Variables recorded were
      demographic and haemodynamic variables, duration of cardiopulmonary bypass and
      aortic clamping, intra- and postoperative urine output, plasma creatinine
      concentration, creatinine clearance and excretion of sodium, albumin, IgG, beta
      glucosaminidase (beta-NAG), and alpha1-microglobulin. Measurements were made
      preoperatively, immediately before and then during and immediately after
      cardiopulmonary bypass, and again at 1, 24, 72 h, 7 and 40 days following
      surgery. RESULTS: Albumin and IgG excretion rose significantly during
      cardiopulmonary bypass (P < 0.05), remaining at these levels at 24 h
      postoperatively. An increase of alpha1-microglobulin and beta-NAG concentrations
      was observed during cardiopulmonary bypass (P < 0.05), which were maintained
      until the seventh postoperative day and remained elevated in some patients at the
      40th postoperative day. This correlated with preoperative diabetes mellitus (P <
      0.001), low cardiac output after cardiopulmonary bypass (P < 0.001) and the
      duration of stay in the intensive care unit (P < 0.001). CONCLUSIONS: The pattern
      of renal dysfunction after cardiopulmonary bypass for myocardial
      revascularization is characterized by temporary renal dysfunction at both
      glomerular and tubular levels with an onset within 24 h of surgery and which
      lasts between 24 h and 40 days, respectively, following surgery.

PMID- 12803261
TI  - Bispectral index monitoring in patients undergoing cardiac surgery under
      cardiopulmonary bypass.
AB  - BACKGROUND AND OBJECTIVE: Monitoring the depth of anaesthesia by the bispectral
      index facilitates the titration of anaesthetic drugs during operation as well as
      assisting in early recovery. We planned to use this index to control the
      administration of anaesthetic agents in order to stabilize haemodynamics and
      promote recovery from anaesthesia in patients undergoing cardiac surgery with
      cardiopulmonary bypass. METHODS: Thirty adult patients undergoing valve
      replacement or coronary artery grafting under cardiopulmonary bypass were studied
      in a prospective, randomized, controlled study. Bispectral index monitoring was
      used in all patients. Patients received isoflurane anaesthesia and boluses of
      morphine: in the study group, anaesthetic depth was controlled using the
      bispectral index and clinical variables. In the control group, the bispectral
      index monitor could not be viewed by the anaesthesiologist. Bispectral index,
      mean arterial pressure and heart rate were noted every 5 min, and the incidence
      of hypotension, hypertension, tachycardia and bradycardia also noted. The time to
      recovery, when patients started obeying commands, was also recorded. RESULTS:
      Patients in the study group had significantly less hypertension and tachycardia
      (P < 0.05) than those in the control group. The time to recovery of consciousness
      was less in the study group than in the control group (n.s., P > 0.05). The
      bispectral index rose significantly in the control group at the time of
      institution and termination of cardiopulmonary bypass (P < 0.05). CONCLUSIONS:
      Anaesthesia controlled by bispectral index monitoring decreases the incidence of
      haemodynamic disturbances and facilitates titration of anaesthetic agents during
      cardiopulmonary bypass and thus may assist recovery from anaesthesia.

PMID- 12803262
TI  - Cerebral vascular reactivity response to anaesthetic induction with propofol in
      patients with intracranial space-occupying lesions and vascular malformations.
AB  - BACKGROUND AND OBJECTIVE: In clinical trials, autoregulation and carbon dioxide
      reactivity are preserved during propofol anaesthesia. Paradoxical increases of
      blood flow velocity during induction of anaesthesia could be demonstrated in
      patients with brain tumours. This study evaluates the effects of propofol on
      cerebral blood flow velocity in patients undergoing surgery for brain tumours and
      vascular malformations. METHODS: Changes in cerebral blood flow velocity after
      the administration of propofol were assessed using bilateral 2 MHz transcranial
      Doppler probes in 47 patients undergoing surgery for brain tumours and in 22
      patients undergoing surgery for aneurysms and angiomas. RESULTS: Flow reduction
      after propofol was slightly less pronounced on the side of the tumour; in
      patients with cerebrovascular lesions, no difference between the two sides was
      detectable. After the administration of propofol a flow increase was present on
      the side of the tumour in 2 patients. In 3 patients with angiomas, the flow
      decrease after the administration of propofol was less pronounced on the side of
      the angioma. Neither observation gave statistical proof of abnormality.
      CONCLUSIONS: The flow changes after propofol may give a hint of cerebrovascular
      reactivity. Further investigations should focus on combined measurements of
      cerebral autoregulation and carbon dioxide reactivity and should focus on
      patients with impaired consciousness to test for reliability.

PMID- 12803263
TI  - Propofol versus remifentanil for monitored anaesthesia care during colonoscopy.
AB  - BACKGROUND AND OBJECTIVE: We conducted an open, prospective, randomized study to
      compare the efficacy, safety and recovery characteristics of remifentanil or
      propofol during monitored anaesthesia care in patients undergoing colonoscopy.
      METHODS: Forty patients were randomly assigned to receive either propofol (1 mg
      kg(-1) followed by 10 mg kg (-1) h(-1), n = 20) or remifentanil (0.5 microg kg(
      1) followed by 0.2 microg kg(-1) min(-1), n = 20). The infusion rate was
      subsequently adapted to clinical needs. RESULTS: In the propofol group, arterial
      pressure and heart rate decreased significantly from the baseline. These
      variables remained unchanged in the remifentanil group, but hypoventilation
      occurred in 55% of patients. Early recovery was delayed in the propofol group (P
      < 0.002). Recovery of cognitive and psychomotor functions was faster in the
      remifentanil group. Fifteen minutes after anaesthesia, the Digit Symbol
      Substitution Test score was 28.6 +/- 12.8 versus 36.2 +/- 9.4 and the Trieger Dot
      Test score was 25.6 +/- 8.1 versus 18.7 +/- 4.1 in the propofol and remifentanil
      groups, respectively (both P < 0.05). Patient satisfaction, using a visual
      analogue scale, was higher in the propofol group (96 +/- 7 versus 77 +/- 21, P <
      0.001). CONCLUSIONS: Remifentanil proved efficient in reducing pain during
      colonoscopy. Emergence times were shorter and the recovery of cognitive function
      was faster with remifentanil compared with propofol. Remifentanil provided a
      smoother haemodynamic profile than propofol; however, the frequent occurrence of
      remifentanil-induced hypoventilation requires the cautious administration of this
      agent.

PMID- 12803264
TI  - Comparison between the Datex-Ohmeda M-NMT module and a force-displacement
      transducer for monitoring neuromuscular blockade.
AB  - BACKGROUND AND OBJECTIVE: The Datex-Ohmeda neuromuscular transmission module (M
      NMT) is a new monitor that is part of the AS/3 anaesthesia monitor. It
      incorporates a mechanosensor, which is a piezoelectric polymer attached to the
      hand. The module was compared with a force transducer in 30 patients requiring
      neuromuscular blockade. METHODS: Anaesthesia was induced with fentanyl and
      propofol, and tracheal intubation was performed without muscle relaxants.
      Neuromuscular blockade was assessed by the test module on one arm and the force
      transducer on the other arm. When the response to train-of-four stimulation had
      been stable in both arms for 3 min, rocuronium 0.2 mg kg(-1) was injected
      intravenously. During recovery from blockade, the train-of-four ratio was
      measured in 15 patients, and the ratio of response to double-burst stimulation in
      the other 15 patients. Data analysis was by difference plots. RESULTS: Both
      devices had acceptable coefficients of repeatability. The M-NMT module was biased
      by + 1.3% (upper limit of agreement 14.2%, lower limit -12.9%) for the recovery
      of the train-of-four ratio, and by + 1.09% (17%, -16%) for the recovery of double
      burst stimulation ratio. CONCLUSIONS: The Datex-Ohmeda M-NMT gives measurements
      that are repeatable and gives good enough correspondence with a force transducer
      that it can be used clinically to assess recovery of neuromuscular blockade, but
      the limits of agreement rule out research applications.

PMID- 12803265
TI  - Time required to achieve a stable cuff pressure by repeated aspiration of the
      cuff during anaesthesia with nitrous oxide.
AB  - BACKGROUND AND OBJECTIVE: When the endotracheal tube cuff is repeatedly aspirated
      to avoid excessive cuff pressure during nitrous oxide anaesthesia, a stable cuff
      pressure is eventually achieved. We assessed the time required to achieve a
      stable cuff pressure after repeated cuff deflation. METHODS: During 67% nitrous
      oxide and oxygen anaesthesia, air-filled cuffs of a standard tracheal tube
      (Mallinckrodt Hi-Contour) were repeatedly deflated every 30 min for the first 3
      or 4 h to inhibit excessive pressure (Groups Def-3 or Def-4, respectively, n = 10
      for each); the cuff pressure was monitored for an additional 3 h. In some
      patients, the study was terminated at 1, 2, 3 and 4 h (n = 6 for each). RESULTS:
      Cuff pressure in Group Def-3, but not in Group Def-4, > 22 mmHg after stopping
      cuff aspiration. Intracuff nitrous oxide concentrations increased during repeated
      cuff deflation and increased further in Group Def-3 during an additional 3 h
      (from 39.8 +/- 4.7% to 44.3 +/- 3.8%; P < 0.05), whereas intracuff nitrous oxide
      concentrations at 4 h were not different from those in Group Def-4 at the end of
      the study (43.7 +/- 4.5% versus 42.3 +/- 4.8%; P = 0.579). CONCLUSIONS: When the
      air-filled cuff of the standard endotracheal tube is repeatedly deflated every 30
      min for 4 h, but not for only 3 h, during nitrous oxide anaesthesia, a stable
      cuff pressure can be achieved without further deflation of the cuff. Our data
      also suggest that achieving an equilibrating nitrous oxide concentration in the
      cuff provides a subsequent stable cuff pressure.

PMID- 12803266
TI  - Clinical test to confirm tracheal intubation: a new method to confirm
      endotracheal intubation in the absence of capnography.
AB  - BACKGROUND AND OBJECTIVE: Advancing an uncut endotracheal tube into the right
      main bronchus produces unilateral breath sounds. We wanted to test the validity
      of using this method to distinguish oesophageal from tracheal intubation.
      METHODS: Forty-two patients were randomized into two groups. The first group was
      randomized to receive an endotracheal tube that was advanced into the right main
      bronchus. The second group of patients had their tracheas intubated as normal and
      then a second endotracheal tube was placed in the oesophagus. Blinded observers
      were then asked to decide by auscultation if the patients had unilateral breath
      sounds or not and if they were bronchial and therefore to decide if endotracheal
      intubation had occurred. RESULTS: Ninety-one per cent of patients (95% CI 0.71
      0.99) intubated in the right main bronchus were correctly identified by
      unilateral breath sounds confirming the usefulness of this test. CONCLUSIONS:
      Advancing an endotracheal tube into the right main bronchus and auscultation of
      unilateral breath sounds is a useful way of confirming tracheal intubation.

PMID- 12803267
TI  - Preliminary experience of combined peri- and retrobulbar block in surgery for
      penetrating eye injuries.
AB  - BACKGROUND AND OBJECTIVE: Regional anaesthesia has not been recommended as an
      anaesthetic method for penetrating eye injuries because it is suspected to
      aggravate the injury already present. After having successfully managed the
      treatment of a penetrating eye injury under combined peri- and retrobulbar block
      in an ASA IV patient, it was decided to evaluate this anaesthetic method further
      in the treatment of such emergency cases. METHODS: Twenty adult patients with
      penetrating eye injuries with a maximum wound length of 8 mm extending up to 4 mm
      posteriorly from the limbus were operated on under combined peri- and retrobulbar
      anaesthesia. Eighteen patients receiving general anaesthesia served as controls.
      RESULTS: The mean (range) volume injected for a satisfactory peribulbar
      retrobulbar block was 7.4 (6.5-8.0) mL, six patients needed an additional
      retrobulbar injection before surgery (2.9, range 2-4, mL). All patients receiving
      regional anaesthesia were satisfied with the anaesthetic method and the surgeons
      considered the surgical conditions as good. No problems relating to local
      anaesthesia were observed or reported by any of the patients. CONCLUSIONS: In the
      hands of an experienced anaesthesiologist and under certain conditions, regional
      anaesthesia appears to be suitable for adult patients having penetrating eye
      injuries.

PMID- 12803268
TI  - Oral premedication with fentanyl may be a safe and effective alternative to oral
      midazolam.
AB  - BACKGROUND AND OBJECTIVE: Although midazolam is commonly given orally to infants
      and small children for premedication, the taste is sometimes unacceptable even
      when mixed with syrup. We tested the efficacy and safety of oral fentanyl
      compared with oral midazolam in a randomized open-label study. METHODS: Fifty-one
      children, aged 12-107 months and weighing 10-25 kg, were randomly assigned to
      fentanyl or midazolam treatment groups. Midazolam (5 mg) or fentanyl (0.1 mg) was
      given orally from a small bottle with a small orifice 30 min before transfer to
      the preoperative holding room. The excitation-sedation conditions of the patients
      were assessed before and after general anaesthesia. RESULTS: The preoperative
      scores did not differ significantly between the two groups. No major
      complications were observed in either group. Postoperative vomiting occurred in 5
      of 27 (18.5%) patients treated with oral fentanyl and in none of 24 of those
      treated with midazolam. CONCLUSIONS: Oral administration of fentanyl 30 min
      before entrance to the holding room for an operation from a bottle with a small
      orifice is a premedication option for children between 1 and 8 yr of age.

PMID- 12803269
TI  - Pain on injection of propofol: comparison of metoprolol with lidocaine.
AB  - BACKGROUND AND OBJECTIVE: Pain is often experienced when propofol is injected,
      and intravenous lidocaine is often effective in preventing such pain. We decided
      to determine whether metoprolol, given before the injection of propofol, is as
      effective as lidocaine in reducing the incidence and severity of the pain.
      METHODS: Ninety patients scheduled for elective surgery under general anaesthesia
      were randomly allocated to one of three groups to receive either metoprolol 2 mg,
      lidocaine 20 mg or saline 2 mL before any propofol was injected. Each patient was
      given one of these agents intravenously via a 20-G cannula on the dorsum of the
      hand whilst the venous drainage was occluded manually, at the middle of the
      forearm, for 45 s. After the occlusion was released, propofol 2.0-2.5 mg kg(-1),
      at room temperature, was injected at 2 mL (20 mg) every 4 s. Pain was assessed
      verbally and scored as none (0), mild (1) or severe (2). RESULTS: The incidence
      of severe pain in the control group (56.7%) was significantly higher than in the
      metoprolol and lidocaine groups (16.6 and 10%, respectively). The number of
      patients who were free of pain was significantly higher in those who had been
      given either metoprolol or lidocaine. CONCLUSIONS: Pretreatment with intravenous
      metoprolol was equally as effective as lidocaine in reducing the pain associated
      with propofol injection.

PMID- 12803271
TI  - Posterior subgluteal approach to block the sciatic nerve: the controversy of
      'which came first, the chicken or the egg' is alive.

PMID- 12803270
TI  - Preoperative oral celecoxib versus preoperative oral rofecoxib for pain relief
      after thyroid surgery.
AB  - BACKGROUND AND OBJECTIVE: The study compared the analgesic efficacy and safety of
      two preoperatively administered cyclo-oxygenase-2 inhibitors, celecoxib and
      rofecoxib. METHODS: Ninety adult patients undergoing thyroid surgery were divided
      into three groups (each n = 30). They were given a single oral dose of placebo,
      celecoxib 200 mg or rofecoxib 50 mg 1 h before induction of anaesthesia. All
      patients received a standard anaesthetic. Intraoperative blood loss was measured.
      Pain scores, sedation scores, heart rate, mean arterial pressure and respiratory
      rate were noted at 0, 1, 2, 4, 6, 12 and 24 h postoperatively. Analgesic
      (meperidine) requirements and adverse effects were recorded during the first
      postoperative 24 h. RESULTS: Compared with placebo, pain scores were
      significantly lower with rofecoxib at all time points (P < 0.05) and were
      significantly lower with celecoxib (P < 0.05) during the first 4 h. Pain scores
      were significantly lower with rofecoxib compared with celecoxib at 6, 12 and 24 h
      (P < 0.05). The average cumulative 24 h meperidine dose was significantly lower
      with both celecoxib (54.9 +/- 34.4mg) and rofecoxib (42.8 +/- 40.9 mg) compared
      with placebo (76.8 +/- 6.2 mg) (P < 0.01 and P < 0.001, respectively). There were
      no differences in the intraoperative blood loss, heart rate, mean arterial
      pressure, respiratory rate, sedation scores and incidence of adverse effects
      among groups. CONCLUSIONS: The preoperative administration of rofecoxib 50 mg and
      less so of celecoxib 200 mg provide a significant analgesic benefit with regard
      to postoperative pain relief and decrease in additional opioid requirements after
      thyroid surgery.

PMID- 12803273
TI  - Spontaneous intracranial hypotension treated with a cervical epidural blood
      patch.

PMID- 12803272
TI  - Breath interval as a continuous measure of opioid effects of intravenous fentanyl
      and alfentanil.

PMID- 12803274
TI  - Pharyngeal necrosis with the laryngeal mask airway.

PMID- 12803275
TI  - More resistance than normal: equipment checks revisited.

PMID- 12803276
TI  - In vivo studies on possible health consequences of genetically modified food and
      feed--with particular regard to ingredients consisting of genetically modified
      plant materials.
AB  - This synopsis reviews published in vivo studies on possible health consequences
      of genetically modified food and feed where the ingredients in question have
      consisted of genetically modified plant materials. The following, however, have
      not been taken into consideration:--ingredients consisting of genetically
      modified microorganisms or parts of animals/fish--ingredients produced by/from
      genetically modified organisms but without any DNA present--studies on
      consequences for the environment or biodiversity--in vitro studies or computer
      simulations. According to a Norwegian report "Gen-mat" (NOU 2000:29), and a more
      recent search in Medline and Citations Index, to our knowledge a total of ten
      studies have been published on the health effects of GM-foods and feeds. In this
      minireview the data made available in these published studies is discussed.

PMID- 12803277
TI  - The (ir)relevance of framing nutrition education messages.
AB  - Persuasive health education messages can either stress the positive consequences
      of performing a healthy behaviour (gain-frame) or the negative consequences of
      not performing a healthy behaviour (loss-frame). Based on studies on topics such
      as sun protection and breast self-examination there is evidence that messages in
      different action frames may differ in persuasive effects. Three randomised
      controlled trials were conducted to test framing effects in nutrition education
      on specific nutrition-related attitudes and intentions. In study 1, effects of
      gain-framed and loss-framed messages were studied among 152 adult education
      students on attitudes and intentions related to fat, fruit and vegetable
      consumption. In study 2 we confronted 149 regular students with differently
      framed messages related to a (more or less fictive) preventive dietary behaviour
      that was expected to be unknown to the study population, intake of flavonoids and
      risk for chronic disease. The impact on attitudes and intentions to use flavonoid
      enriched spreads was studied. In study 3 we studied the effects of differently
      framed messages on attitudes and intentions related to more immediate and more
      personally relevant diet nutrition behaviour: folic acid supplement use before
      and during pregnancy among 100 female students. No significant differences in
      attitudes or intentions to perform the preventive nutrition behaviours were found
      between the gain-frame conditions and the loss-frame conditions in all three
      studies. The (lack of) effects were not moderated by factors such as perceived
      personal relevance, credibility or novelty of the information, or the perceived
      importance of the topic addressed. The results of the present studies suggest
      that action-frame choice has a very limited impact on the effectiveness of
      nutrition education in changing precautionary motivation.

PMID- 12803278
TI  - A study on under five nutritional status and its determinants in a semi-rural
      community of Ile-Ife, Osun State, Nigeria.
AB  - Ten variables were assessed as they influence the under five (U5) nutritional
      status of children at Oranfe, a semi-rural community in Ife East Local Government
      Area of Osun state, Nigeria. The two types of protein energy malnutrition (PEM)
      that are prevalent in the community are stunting and wasting. Of the 230 children
      assessed using Waterlow's technique, 23% and 22.6% were stunted and wasted
      respectively. The results confirmed that mothers' educational level, age, parity,
      types of family and children's immunization status and age are some of the key
      determinants of nutritional status of U5 children. The intensification of
      exclusive breast feeding, female education, a compulsory food demonstration unit
      in all health centres, use of complementary feeds from 7 months upwards, growth
      monitoring and promotion are some of the strategies to reduce the high prevalence
      of PEM in both rural and urban areas of developing countries.

PMID- 12803279
TI  - Breakfast food patterns among urban and rural Croatian schoolchildren.
AB  - The aim of this study was to report breakfast food patterns among the rural and
      urban Croatian schoolchildren in the post-war socioeconomic changes. A
      quantitative Food Frequency Questionnaire was used. Subjects were 7-18 year old
      schoolchildren (815 from urban and 375 from rural areas). The average energy
      intake was 27.5 and 23.0% of the Recommended Dietary Allowance (RDA) in the urban
      and rural area respectively. Urban subjects tend to choose healthier options when
      older, while the rural subjects displayed the opposite (significantly correlated
      age with energy intake (% RDA) and dietary fibre intake (% of 'age + 5' rule).
      The same applied to age versus iron intake (urban positive, rural negative
      correlation). Breakfasts providing 20-30% RDA for energy and more than 300 mg of
      calcium were consumed by 20.7 and 32.4% of the urban and rural subjects
      respectively. Cereal products and milk and dairy products were the major
      breakfast constituents everywhere. Meat and its products, and eggs seem to be
      uncommon breakfast foods. The urban subjects had a more adequate energy intake at
      breakfast, but better food choices were observed among rural subjects.

PMID- 12803280
TI  - An advanced artificial intelligence tool for menu design.
AB  - The computer-assisted menu design still remains a difficult task. Usually
      knowledge that aids in menu design by a computer is hard-coded and because of
      that a computerised menu planner cannot handle the menu design problem for an
      unanticipated client. To address this problem we developed a menu design tool,
      MIKAS (menu construction using incremental knowledge acquisition system), an
      artificial intelligence system that allows the incremental development of a
      knowledge-base for menu design. We allow an incremental knowledge acquisition
      process in which the expert is only required to provide hints to the system in
      the context of actual problem instances during menu design using menus stored in
      a so-called Case Base. Our system incorporates Case-Based Reasoning (CBR), an
      Artificial Intelligence (AI) technique developed to mimic human problem solving
      behaviour. Ripple Down Rules (RDR) are a proven technique for the acquisition of
      classification knowledge from expert directly while they are using the system,
      which complement CBR in a very fruitful way. This combination allows the
      incremental improvement of the menu design system while it is already in routine
      use. We believe MIKAS allows better dietary practice by leveraging a dietitian's
      skills and expertise. As such MIKAS has the potential to be helpful for any
      institution where dietary advice is practised.

PMID- 12803281
TI  - The natural cure of coronary heart disease.
AB  - Following the development of coronary heart disease in 1989 I was introduced to
      an alumnus of the Pritikin Longevity Center in California and I adopted the
      regimen of diet and exercise. Within five months I was able to abandon all
      medication and was symptom free. My medical colleagues maintained that, because I
      had recovered, the Consultant's diagnosis must have been wrong--there can be no
      cure of coronary heart disease by lifestyle changes alone. As a result of my
      experience I decided to review the literature to study the natural history of
      coronary heart disease. My findings strongly suggest that the increase in
      incidence in the last hundred years from virtually nil to epidemic proportions is
      due to lifestyle changes and that the disease can be reversed. I list a number of
      doctors who have influenced large numbers of people to change their lifestyles
      with great success. They have utilised mainly plant-based diets whose composition
      is the same or similar to that which Pritikin originally used and which is still
      extant at the Longevity Center. I conclude by suggesting that the possibility of
      reversal of coronary heart disease has profound implications for its treatment
      with enormous potential savings for the National Health Service.

PMID- 12803282
TI  - Effect of domestic processing and cooking methods on total, HCl extractable iron
      and in vitro availability of iron in bathua and fenugreek leaves.

PMID- 12803283
TI  - The effects of chocolates given by patients on the well-being of nurses and their
      support staff.
AB  - Chocolate has a number of extremely appealing sensory qualities, and often are
      given by patients to those working in hospital wards as a token of their
      gratitude. This study examines whether this has any harmful effects. Eighty nine
      qualified nurses, 21 ward assistants, and 18 nursing students completed a
      structured questionnaire, showing that on average 5.4 chocolates were eaten each
      day. About 2/3 of the recipients ate 1-5 chocolates a day, while a few (3%) ate
      more than 20 per day. The most common reason given for eating them was simply
      because they were there. However, a quarter felt that a healthier alternative
      would be an adequate alternative gift. Around a third of those surveyed felt that
      the chocolates had a detrimental effect on their well-being. It is unlikely that
      chocolates will ever be scarce on hospital wards because there is a never-ending
      supply from grateful patients. Consequently, it will be difficult to restructure
      the chocolate-eating habits of those working on hospital wards.

PMID- 12803284
TI  - The influence of teent (Capparis decidua) on human plasma triglycerides, total
      lipids and phospholipids.
AB  - Teent is an unripe fruit of Ker (Capparis decidua) a xerophytic bush. It contains
      15.1% protein and 42.88% fibre. Being a rich source of fibre, the process for
      preparation of teent powder and other recipes were standardized for feeding
      hyperlipidemic subjects. The diet of 15 hyperlipidemic adults (40-60 yrs.) was
      supplemented with teent for three months and plasma triglycerides, total lipids
      and phospholipids were analysed before and at the end of the experiment.
      Significant reductions in plasma triglycerides, total lipids and phospholipids
      concentration were noticed.

PMID- 12803285
TI  - Human evolution.

PMID- 12803286
TI  - Asthma.

PMID- 12803287
TI  - Neural network for photoplethysmographic respiratory rate monitoring.
AB  - The reflection mode photoplethysmographic (PPG) signal was studied with the aim
      of determining respiratory rate. The PPG signal includes respiratory synchronous
      components, seen as frequency modulation of the heart rate (respiratory sinus
      arrhythmia), amplitude modulation of the cardiac pulse and respiratory-induced
      intensity variations (RIIVs) in the PPG baseline. PPG signals were recorded from
      the foreheads of 15 healthy subjects. From these signals, the systolic wave-form,
      diastolic waveform, respiratory sinus arrhythmia, pulse amplitude and RIIVs were
      extracted. Using basic algorithms, the rates of false positive and false negative
      detection of breaths were calculated separately for each of the five components.
      Furthermore, a neural network was assessed in a combined pattern recognition
      approach. The error rates (sum of false positive and false negative breath
      detections) for the basic algorithms ranged from 9.7% (pulse amplitude) to 14.5%
      (systolic waveform). The corresponding values for the neural network analysis
      were 9.5-9.6%. These results suggest the use of a combined PPG system for
      simultaneous monitoring of respiratory rate and arterial oxygen saturation (pulse
      oximetry).

PMID- 12803288
TI  - Respiratory variations in the reflection mode photoplethysmographic signal.
      Relationships to peripheral venous pressure.
AB  - Photoplethysmography (PPG) is a non-invasive optical way of measuring variations
      in blood volume and perfusion in the tissue, used in pulse oximetry for instance.
      Respiratory-induced intensity variations (RIIVs) in the PPG signal exist, but the
      physiological background is not fully understood. Respiration causes variations
      in the blood volume in the peripheral vascular bed. It was hypothesised that the
      filling of peripheral veins is one of the important factors involved. In 16
      healthy subjects, the respiratory synchronous variations from a PPG reflection
      mode signal and the peripheral venous pressure (PVP) were recorded. Variations of
      tidal volume, respiratory rate and contribution from abdominal and thoracic
      muscles gave significant and similar amplitude changes in both RIIV and the
      respiratory variation of PVP (p<0.01). The highest amplitudes of both signals
      were found at the largest tidal volume, lowest respiratory rate and during mainly
      thoracic breathing, respectively. The coherence between PVP and RIIV signals was
      high, the median (quartile range) being 0.78 (0.42). Phase analysis showed that
      RIIV was usually leading PVP, but variations between subjects were large.
      Although respiratory-induced variations in PVP and PPG showed a close correlation
      in amplitude variation, a causal relationship between the signals could not be
      demonstrated.

PMID- 12803289
TI  - Analysis and processing of laser Doppler perfusion monitoring signals recorded
      from the beating heart.
AB  - Laser Doppler perfusion monitoring (LDPM) can be used for monitoring myocardial
      perfusion in the non-beating heart. However, the movement of the beating heart
      generates large artifacts. Therefore the aim of the study was to develop an LDPM
      system capable of correlating the laser Doppler signals to the cardiac cycle and
      to process the signals to reduce the movement artifacts. Measurements were
      performed on three calves, both on the normal beating heart and during occlusion
      of the left anterior descending coronary artery (LAD). The recorded LDPM signals
      were digitally processed and correlated to the sampled ECG. Large variations in
      the output (perfusion) and DC signals during the cardiac cycle were found, with
      average coefficients of variation of 0.36 and 0.14 (n = 14), respectively.
      However, sections with a relatively low, stable output signal were found in late
      diastole, where the movement of the heart is at a minimum. Occlusion of the LAD
      showed the importance of recording the laser Doppler signals at an appropriate
      point in the cardiac cycle, in this case late systole, to minimise movement
      artifacts. It is possible to further reduce movement artifacts by increasing the
      lower cutoff frequency when calculating the output signal.

PMID- 12803290
TI  - On-line monitoring of solutes in dialysate using wavelength-dependent absorption
      of ultraviolet radiation.
AB  - The aim of the study was to assess the wavelength dependence of the UV absorbance
      during monitoring of different compounds in the dialysate. UV absorbance was
      determined by using a double-beam spectrophotometer on dialysate samples taken at
      pre-determined times during dialysis, over a wavelength range of 180-380 nm.
      Concentrations of several removed substances, such as urea, creatinine, uric
      acid, phosphate and beta2-microglobulin, were determined in the blood and in the
      spent dialysate samples using standard laboratory techniques. Millimolar
      extinction coefficients, for urea, creatinine, monosodium phosphate and uric acid
      were determined during laboratory bench experiments. The correlation between UV
      absorbance and substances both in the dialysate and in the blood was calculated
      at all wavelengths. A time-dependent UV absorbance was determined on the
      collected dialysate samples from a single dialysis session over a wavelength
      range of 200-330 nm. The highest contribution from observed compounds relative to
      the mean value of the absorbance was found around 300 nm and was approximately
      70%. The main contribution to the total absorbance from uric acid was confirmed
      at this wavelength. The highest correlation for uric acid, creatinine and urea
      was obtained at wavelengths from 280 nm to 320 nm, both in the spent dialysate
      and in the blood. The wavelength region with the highest correlation for
      phosphate and beta2-microglobulin, with a suitable UV-absorbance dynamic range,
      was from 300 to 330 nm. In the wavelength range of 220-270 nm the highest
      absorbance sensitivity for the observed substances was obtained. A suitable
      wavelength range for instrumental design seems to be around 290-330 nm. The
      relatively high correlation between UV absorbance and the substances in the spent
      dialysate and in the blood indicates that the UV-absorbance technique can
      estimate the removal of several retained solutes known to accumulate in dialysis
      patients.

PMID- 12803292
TI  - Precision, comfort and mechanical performance of the Quadriso-tester, a
      quadriceps force measuring device.
AB  - The mechanical performance, repeatability and comfort of the Quadriso-tester,
      which assesses isometric knee extensor muscle strength, were examined. Twenty
      healthy subjects and 20 patients treated for unilateral anterior ligamenta
      cruciata insufficiency were tested. Intra-rater repeatability was determined by
      the testing and retesting of subjects and calculation of the intra-class
      correlation coefficient and the mean difference between test and retest values.
      The comfort level was determined a questionnaire. Measuring time was recorded,
      and the relationship between knee angle and extension moment was plotted.
      Strength and stiffness were determined using the finite element method. Intra
      rater repeatability was high; the intra-class correlation coefficient of the
      right and left leg was 0.90 and 0.91, respectively; the coefficient of variation
      was 6.4 and 6.0%, respectively. The median comfort score of the healthy subjects
      was 7, and that of the patients was 9. Measuring time remained within 30 min.
      Misalignment of the knee and sidebar axis disturbed the relationship between knee
      angle and extension moment Strength and stiffness were higher than required. In
      conclusion, the Quadriso-tester is a comfortable and fast device to determine
      quadriceps force with a high repeatability. The knee and sidebar axis should be
      well aligned.

PMID- 12803291
TI  - Large-scale expansion of mammalian neural stem cells: a review.
AB  - A relatively new approach to the treatment of neurodegenerative diseases is the
      direct use of neural stem cells (NSCs) as therapeutic agents. The expected demand
      for treatment from the millions of afflicted individuals, coupled with the
      expected demand from biotechnology companies creating therapies, has fuelled the
      need to develop large-scale culture methods for these cells. The rapid pace of
      discovery in this area has been assisted through the use of animal model systems,
      enabling many experiments to be performed quickly and effectively. This review
      focuses on recent developments in expanding human and murine NSCs on a large
      scale, including the development of new serum-free media and bioreactor
      protocols. In particular, engineering studies that characterise important scale
      up parameters are examined, including studies examining the effects of long-term
      culture of NSCs in suspension bioreactors. In addition, recent advances in the
      human NSC system are reviewed, including techniques for the evaluation of NSC
      characteristics.

PMID- 12803293
TI  - Systematic characterisation of silicon-embedded accelerometers for
      mechanomyography.
AB  - Silicon soft suction sockets (roll-on sleeves) currently used in passive
      prostheses for below-elbow amputees could also be used in externally powered
      prostheses, enhancing their functionality and comfort. However, as it is
      extremely difficult to hold currently used electromyography (EMG) sensors in
      place reliably within a silicon socket, an alternative measurement of muscular
      activity as the control input is necessary. Mechanomyography (MMG) is the
      epidermal measurement of the low-frequency vibrations produced by a contracting
      muscle. MMG sensors do not have to be in direct contact with the skin. Moreover,
      the embedding of sensors in the roll-on sleeve may also solve attachment issues,
      making sensor placement flexible. Therefore the objective was to determine the
      feasibility of recording MMG signals using silicon-embedded, micro-machined
      accelerometers. Fifteen embedded accelerometers were excited with predefined
      vibration patterns. The signal-to-noise ratio (SNR) and frequency response of
      each sample were measured and compared with those of non-embedded accelerometers.
      The SNR of embedded samples (approximately equal to 19 dB) was significantly
      higher than that of non-embedded samples (approximately equal to 12 dB), owing to
      the considerable mechanical damping effect of the silicon in the 300-900 Hz
      bandwidth (p=0.0028). This has implications for the application of silicon
      embedded accelerometers for externally powered prosthesis control.

PMID- 12803294
TI  - Detection of daily physical activities using a triaxial accelerometer.
AB  - Triaxial accelerometers have been employed to monitor human movements in a
      variety of circumstances. The study considered the use of data from a single
      waist-mounted triaxial accelerometer to distinguish between activity states and
      rest A method using acceleration magnitude was applied to data collected from 26
      normal subjects performing sit-to-stand and stand-to-sit transitions and walking.
      The effects of three parameters were investigated: the length n of a smoothing
      median filter, the width w of the averaging window used to process the signal and
      the value of the acceleration magnitude threshold th. These were found to be
      inter-related, and sets of parameters that resulted in accurate discrimination
      were determined by the relationship between th and the product of w and n, and by
      the relationship between n and w. The subjects were randomly divided into control
      (N = 13) and test (N = 13) groups. Optimum parameter sets were determined using
      the control group. Eleven sets of parameters yielded the same optimum results of
      a sensitivity of 1.0 and a specificity of 0.96 in the control group. Upon
      application to the test group, using these parameters, the system successfully
      distinguished between activity and rest, giving sensitivities greater than 0.98
      and specificities between 0.88 and 0.94.

PMID- 12803295
TI  - Signal processing technique for non-invasive real-time estimation of cardiac
      output by inductance cardiography (thoracocardiography).
AB  - Inductance cardiography (thoracocardiography) non-invasively monitors changes in
      stroke volume by recording ventricular volume curves with an inductive
      plethysmographic transducer encircling the chest at the level of the heart.
      Clinical application of this method has been hampered, as data analysis has not
      been feasible in real time. Therefore a novel, real-time signal processing
      technique for inductance cardiography has been developed. Its essential concept
      consists in performance of multiple tasks by several, logically linked signal
      processing modules that have access to common databases. Based on these
      principles, a software application was designed that performs acquisition,
      display, filtering and ECG-triggered ensemble averaging of inductance signals and
      separates cardiogenic waveforms from noise related to respiration and other
      sources. The resulting ventricular volume curves are automatically analysed.
      Performance of the technique for monitoring cardiac output in real time was
      compared with thermodilution in four patients in an intensive care unit. The bias
      (mean difference) among 76 paired thoracocardiographic and thermodilution derived
      changes in cardiac output was 0%; limits of agreement (+/- 2 SD of the bias) were
      +/- 25%. It is concluded that the proposed signal processing technique for
      inductance cardiography holds promise for non-invasive, real-time estimation of
      changes in cardiac output.

PMID- 12803296
TI  - Non-invasive imaging of optical parameters of biological tissues.
AB  - The normalised back-scattered intensity (NBI) profiles at various locations on
      the forearms of ten human subjects were obtained by moving the multi-probe of a
      laser reflectometer. The statistical analysis of the NBI data showed that the
      variation in the NBI was significantly higher at the ulnar region compared with
      that at other regions. For determination of the scattering (mus) and absorption
      (mus) coefficients and the anisotropy parameter g at each location on the
      forearm, these profiles were matched with the NBI profiles simulated by a Monte
      Carlo procedure (chi(2)0.99). For the reconstruction of images of variation of
      these parameters, the averaged values of mua, mus, and g at all locations on the
      forearms of the subjects were determined. The absorption coefficient had a
      minimum (1.92 cm(-1)) and maximum (2.21cm(-1)) at the wrist and the lateral
      region of the forearm, respectively. The scattering coefficient had a maximum
      (194 cm(-1)) at the medial side and near the elbow, and a minimum (186 cm(-1)) at
      the lateral side of the forearm. Similar changes in the anisotropy parameter were
      also observed. By interpolation of the data of each parameter on a 100 x 100
      image matrix and after median filtering, colour-coded images of the variation in
      the optical parameters were constructed. These images could be useful for
      diagnostic and therapeutic applications of lasers.

PMID- 12803297
TI  - Hepatic bipolar radiofrequency ablation creates coagulation zones close to blood
      vessels: a finite element study.
AB  - Radiofrequency (RF) ablation has become an important means of treatment of non
      resectable primary and metastatic liver tumours. Recurrence of treated tumours is
      associated with cancer cell survival next to blood vessels. The paper examines
      the performance of classical monopolar, and two configurations of bipolar, RF
      ablation using a LeVeen ten-prong catheter. Finite element method models of
      monopolar and bipolar configurations were created at 5 mm distance from a vessel
      of the size of a typical portal vein (10 mm diameter). In one bipolar
      configuration, the probes were oriented in the same axial direction (asymmetric
      configuration); in the second bipolar configuration, the two probes were facing
      each other (symmetric configuration). The distribution of temperature and current
      density was analysed for three different flow conditions: normal flow, reduced
      flow due to portal hypertension and high flow. For normal flow, the distance
      between the formed coagulation zone and the blood vessel was 1.8 mm for
      monopolar, 1 mm for asymmetric bipolar, and 0.2 mm for symmetric bipolar,
      configurations. Symmetric bipolar RF ablation creates coagulation zones
      significantly closer to blood vessels compared with monopolar RF ablation. This
      may reduce tumour cell survival next to blood vessels and reduce recurrence
      rates.

PMID- 12803298
TI  - Combined near-infrared spectroscopy and multifrequency bio-impedance
      investigation of skin alterations in diabetes patients based on multivariate
      analyses.
AB  - A group of 34 diabetic men, with different degrees of diabetes complications,
      including skin changes, were studied by near-infrared (NIR) spectroscopy and
      total body multi-frequency bio-impedance analyses (MFBIA-body). Skin reflectance
      spectra were measured with a fibre-optic probe in four locations (sites): hand,
      arm, leg and foot. As control subjects, a group of 23 healthy males were also
      measured. A combined multivariate analysis of the two types of spectrum was
      performed. It was concluded that the NIR method has the potential to detect
      diabetes-related skin conditions and also that the combination of the two
      techniques provides a higher potential for classification and discrimination of
      the skin conditions, with correct classification increasing from 63% to 85%.

PMID- 12803299
TI  - Single motor unit analysis from spatially filtered surface electromyogram
      signals. Part I: spatial selectivity.
AB  - The aim of the study was to compare experimentally, on the basis of single motor
      unit (MU) activities, the selectivity of different spatial filters commonly used
      to detect surface electromyogram (EMG) signals. Surface EMG signals were recorded
      from the biceps brachii and the upper trapezius muscle of five subjects using a
      two-dimensional (2D) electrode array consisting of 16 pin electrodes. The
      subjects performed isometric contractions at different elbow angles and shoulder
      abduction and flexion. The same monopolar surface EMG signals were filtered using
      longitudinal single and double differential, transverse single and double
      differential and normal double differential filters. From the single MU action
      potentials, extracted by automatic EMG decomposition, indexes of transverse
      (perpendicular with respect to the fibre direction) and longitudinal (along the
      fibre direction) selectivity were computed. The number of detected MUs was 46 for
      the upper trapezius, with the arms held in the sagittal plane, and 52 when the
      arms were held in the frontal plane; 85 MUs were identified from the biceps
      brachii contractions. The results showed that transverse selectivity was
      significantly higher for the 2D and transverse one-dimensional (1D) filters with
      respect to the 1D longitudinal filters, whereas longitudinal selectivity was
      higher (i.e. MU action potentials were shorter) for the 2D filter and the
      longitudinal double differential filter. In particular, the relative attenuation
      of potential amplitude moving 5 mm from the source was, on average (for the two
      muscles), 16.5% for the least selective filter in the transverse direction
      (longitudinal single differential) and 35.7% for the most selective one in the
      same direction (transverse double differential). The MU action potential duration
      was, on average, 13.8 ms for the most selective filter in the longitudinal
      direction (longitudinal double differential) and 18.7 ms for the least selective
      one (transverse double differential). The normal double differential filter
      resulted in spatial selectivity indexes that ware not statistically different in
      the two directions from those of the best filters in each direction.

PMID- 12803300
TI  - Single motor unit analysis from spatially filtered surface electromyogram
      signals. Part 2: conduction velocity estimation.
AB  - The aim of the study was to compare experimentally conduction velocity (CV)
      estimates obtained with different estimation methods based on surface
      electromyogram (EMG) signals detected using five spatial filters. The filters
      investigated were the longitudinal single and double differential, transverse
      single and double differential, and normal double differential. The same surface
      EMG signals detected as described in Part 1 were used in this work. CV was
      estimated with four commonly used delay estimation techniques, i.e. from the
      distance between the peak values of two waveforms (with and without polynomial
      interpolation around the peak), and by the maximum likelihood estimate (MLE)
      based on two or more surface EMG channels. The average standard deviation of CV
      estimation (for all the MUs and the two muscles together) was 0.61 m s(-1) and
      0.79 m s(-1) for the peak method, with and without interpolation, respectively,
      and 0.50 m s(-1) and 0.31 m s(-1) for the MLE method, from two and more surface
      EMG channels, respectively. Moreover, the mean of CV estimates varied by as much
      as 1 m s(-1) depending on the spatial filter used and the method adopted for CV
      estimation. Considering the dependence on the spatial filter only, the average
      (over all estimation methods) CV estimates obtained with the five spatial filters
      were 4.32 m s(-1) (normal double differential), 4.23 m s(-1) (longitudinal double
      differential), 4.61 m s(-1) (transverse double differential), 4.64 m s(-1)
      (transverse single differential) and 4.03 m s(-1) (longitudinal single
      differential). It was concluded that the comparison of single MU CV values
      obtained in different studies is critical if different spatial filters and
      processing techniques are used for their estimation. Higher estimates of CV were
      attributed to a smaller reduction in non-travelling signal components and thus
      were assumed to be positively biased.

PMID- 12803301
TI  - Bluetooth wireless database for scoliosis clinics.
AB  - A database system with Bluetooth wireless connectivity has been developed so that
      scoliosis clinics can be run more efficiently and data can be mined for research
      studies without significant increases in equipment cost. The wireless database
      system consists of a Bluetooth-enabled laptop or PC and a Bluetooth-enabled
      handheld personal data assistant (PDA). Each patient has a profile in the
      database, which has all of his or her clinical history. Immediately prior to the
      examination, the orthopaedic surgeon selects a patient's profile from the
      database and uploads that data to the PDA over a Bluetooth wireless connection.
      The surgeon can view the entire clinical history of the patient while in the
      examination room and, at the same time, enter in any new measurements and
      comments from the current examination. After seeing the patient, the surgeon
      synchronises the newly entered information with the database wirelessly and
      prints a record for the chart. This combination of the database and the PDA both
      improves efficiency and accuracy and can save significant time, as there is less
      duplication of work, and no dictation is required. The equipment required to
      implement this solution is a Bluetooth-enabled PDA and a Bluetooth wireless
      transceiver for the PC or laptop.

PMID- 12803302
TI  - Biological and mechanical quality of red blood cells cultured from human
      umbilical cord blood stem cells.
AB  - Human umbilical cord blood (CB) has moved from the status of biological waste to
      that of a valuable source of haematopoietic stem (HS) cells. There are
      potentially three major clinical applications for HS cells and ex vivo-expanded
      HS cells: reconstitution of haematopoiesis in patients undergoing chemotherapy;
      gene therapy (e.g. in thalassaemia, sickle cell anaemia); and large-scale
      production of mature blood cells. Erythropoiesis is accomplished by highly
      complex interactions of haematopoietic progenitor cells, stromal cells and
      cytokines in the bone marrow. Among them, erythropoietin is the principal
      regulator. Ex vivo cell culture experiments to obtain mature red blood cells were
      the focus of this study. Attempts to elucidate appropriate medium components and
      amounts of haematopoietic growth factors were successful: enucleated and
      haemoglobin-filled erythroid cells were obtained from primitive HS cells.
      Dimethylsulphoxide (DMSO) was found to be of particular importance as an
      efficient differentiation inducer. The differentiation process was followed
      microscopically and by fluorescence-activated cell sorting (FACS). Using the
      micropipette aspiration technique, the elastic properties of erythroid cells were
      evaluated as erythropoiesis progressed. Discocyte-like cells, comprising
      reticulocytes and finally differentiated red blood cells, showed an about ten
      fold higher membrane shear modulus compared with control cells.

PMID- 12803303
TI  - Altered impedance during pigment aggregation in Xenopus laevis melanophores.
AB  - Melanophores are dark-brown pigment cells located in the skin of amphibia, fish
      and many invertebrates. The skin colour of these organisms is regulated by the
      translocation of pigment organelles, and the pigment distribution can be altered
      by external stimuli. The ability to change colour in response to stimuli makes
      these cells of interest for biosensing applications. It was investigated whether
      pigment aggregation in Xenopus laevis melanophores can be detected by impedance
      measurements performed in transparent microvials. The results show that cell
      attachment, cell spreading and pigment aggregation all resulted in impedance
      changes, seen particularly at the highest frequency tested (10 kHz). The
      mechanisms behind the impedance changes were investigated by the addition of
      latrunculin or melatonin, both of which cause pigment aggregation. The
      latrunculin-induced aggregation was associated with cell area decrease and
      filamentous actin (F-actin) breakdown, processes that can influence the
      impedance. Lack of F-actin breakdown and an increase in cell area during
      melatonin-induced aggregation suggest that some other intracellular process also
      contributes to the impedance decrease seen for melatonin. It was shown that
      impedance measurements reflect not only cell attachment and cell spreading, but
      also intracellular events.

PMID- 12803304
TI  - Tissue engineering of the intervertebral disc with cultured annulus fibrosus
      cells using atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS
      scaffold).
AB  - The objective of the study was to investigate the regeneration of intervertebral
      discs after laser discectomy using tissue engineering procedures. Annulus
      fibrosus (AF) cells from the intervertebral discs of Japanese white rabbits were
      cultured in an atelocollagen honeycomb-shaped scaffold with a membrane seal
      (ACHMS scaffold), to produce a high-density, three-dimensional culture for up to
      3 weeks. Although the DNA content in the scaffold increased at a lower rate than
      that in the monolayer culture, expression of type II collagen and
      glycosaminoglycan accumulation in the scaffold were at higher levels than in the
      monolayer. The AF cells that had been cultured in the scaffold for 7 days were
      allografted into the lacunae of intervertebral discs of recipients (40 rabbits,
      14-16 weeks old; average weight, 3.2 kg), whose nucleus pulposus (NP) had been
      vaporised with an ICG dye-enhanced laser. The allografted cultured AF cells
      survived and produced hyaline-like cartilage. Furthermore, the narrowing of the
      intervertebral disc space of the cell-containing scaffold insertion groups was
      significantly inhibited after 12 post-operative weeks.

PMID- 12803305
TI  - Enhanced functions of osteoblasts on nanostructured surfaces of carbon and
      alumina.
AB  - It is of the utmost importance to increase the activity of bone cells on the
      surface of materials used in the design of orthopaedic implants. Increased
      activity of such cells can promote either integration of these materials into
      surrounding bone or complete replacement with naturally produced bone if
      biodegradable materials are used. Osteoblasts are bone-producing cells and, for
      that reason, are the cells of interest in initial studies of new orthopaedic
      implants. If these cells are functioning normally, they lay down bone matrix onto
      both existing bone and prosthetic materials implanted into the body. It is
      generally accepted that a successful material should enhance osteoblast function,
      leading to more bone deposition and, consequently, increased strength of the
      interface between the material and juxtaposed bone. The present study provided
      the first evidence of greater osteoblast function on carbon and alumina
      formulations that mimic the nano-dimensional crystal geometry of hydroxyapatite
      found in bone.

PMID- 12803306
TI  - The significance of quality of life in health care.
AB  - This paper compares a traditional biomedical model with an outcomes model for
      evaluating health care. The traditional model emphasizes diagnosis and disease
      specific outcomes. In contrast, the outcomes model emphasizes life expectancy and
      health-related quality of life. Although the models are similar, they lead to
      different conclusions with regard to some interventions. For some conditions,
      diagnosis and treatment may reduce the impact of a particular disease without
      extending life expectancy or improving quality of life. Older individuals with
      multiple co-morbidities may not benefit from treatments for a particular disease
      if competing health problems threaten life or reduce quality of life. In
      preventive medicine, diagnosis of disease is made more difficult because of
      ambiguity, uncertainty, lead-time bias, and length bias. In some circumstances,
      successful diagnosis and treatment may actually reduce life expectancy or overall
      life quality. Example applications of the outcomes model from clinical policy
      analysis, individual decision making and shared decision-making are offered. The
      outcomes model has received little attention in dental health care but may have
      parallels to applications in other areas of medicine.

PMID- 12803307
TI  - Measuring quality of life in the mentally ill.
AB  - It has been our experience that it is easier to measure quality of life among
      persons with serious mental illness than it is to intervene to improve it. This
      article presents background and historical context of service delivery to persons
      with severe mental illness. We then examine approaches to assessing outcomes of
      services, especially quality of life. We conclude with an illustration and
      discussion of dilemmas in measuring quality of life in this vulnerable
      population.

PMID- 12803308
TI  - Social support and quality of life.
AB  - Social support is a broad term, which includes the supportive ways that different
      people behave in the social environment. Structural measures of the environment
      deal with the mere existence of social relationships. Functional measures refer
      to the resources that people within an individual's social network provide.
      Structural support shows a linear relation to quality of life; the functional
      aspects of support demonstrate the stress-buffering hypothesis. One of the main
      focuses of this article is to help researchers determine what aspects of social
      relationships or what types of support need to be measured and to consider the
      mechanisms by which support might influence quality of life. Also addressed is
      how to translate the correlational research on social support and quality of life
      into the field of support interventions, taking into account individual and
      situational differences.

PMID- 12803309
TI  - Family burden and quality of life.
AB  - Providing care to family members dealing with chronic illness may result in
      feelings of burden or strain for caregivers that can diminish their quality of
      life. This article examines objective and subjective dimensions of family burden,
      and the extent to which illness characteristics and contextual variables have
      been found to contribute to caregiver stress for different chronic illnesses.
      After discussing some of the problems in the conceptualization and measurement of
      caregiving burden, it suggests several important directions for future research,
      including further clarification of generic versus specific factors affecting
      caregiver burden, greater understanding of contextual variables, the impact of
      other roles, and examining changes in caregiving demands over the illness course.

PMID- 12803310
TI  - The impact of behavior on quality of life.
AB  - The focus of my article centers on two main issues: why exercise is important and
      how to help people succeed in an exercise program that initially fails. In
      keeping with the theme of the conference, in the eye of the beholder, I thought
      that I might begin my talk with an orientation stemming from views by the late
      philosopher of science, Thomas Kuhn. Kuhn, who coined the phrase paradigm shift,
      referred, in his paper on the Essential Tension [The Third University of Utah
      Research Conference on the Identification of Scientific Talent, Salt Lake City:
      University of Utah Press, 1959], to the German term, einstellungen, as a way of
      seeing and interpreting objects in our world. Each person has a personal way of
      seeing based upon training, orientation, experiences, and daily problems. In my
      field, we have spent the last 20 years trying to reach a consensus about the
      benefits of physical activity. Yet, during that time we have known that only 10
      25% of adults living in free market societies are active enough in their leisure
      time to reap those benefits. Hopefully, now we will follow Kuhn's advice and also
      consider the idea of pre-consensus, in which we diverge from existing policies to
      forge new policies designed to better deliver physical activity to the population
      to enhance the quality of life.

PMID- 12803311
TI  - Studies of the inner life: the impact of spirituality on quality of life.
AB  - This article defines spirituality and relates the importance of spirituality to
      understanding quality of life. Spirituality is examined through organizational
      religious activities, non-organizational activities and/or as an expression of
      faith. Spirituality as a variable in the study of quality of life is not a new
      concept; however, it has returned to the scene during recent years, and has gone
      through an evolutionary process.

PMID- 12803314
TI  - Measuring health: improving the validity of health assessments.
AB  - A large number of test batteries, instruments, indices and scales promise to
      provide reliable and valid information about an individual's health status. It is
      often neglected, however, that the data gathered using these measures are based
      entirely on self-reports and are susceptible to a variety of biasing factors.
      This is of particular concern for health research because many questions are
      inherently ambiguous and require considerable interpretive work on the part of
      the respondent. A single term may cover a wide range of health-related symptoms,
      experiences, or events, making health-related questions highly susceptible to
      contextual influences. This article discusses a number of possible influences on
      individual responses and suggests several determinants of self-report validity.
      The paper is organized into two major parts. The first part demonstrates that the
      validity of survey responses can be enhanced substantially when knowledge about
      conversational dynamics is taken into account during the design stage of the
      questionnaire. The second part argues that respondents are motivated and able to
      provide valid information about their overall health status. The validity of
      global single-item measures of health status is examined, and a cognitive model
      is introduced that outlines how subjective health evaluations are made.

PMID- 12803312
TI  - Personality and quality of life: the importance of optimism and goal adjustment.
AB  - This article concerns the relations between personality and quality of life. In
      the first part, we discuss different conceptualizations of personality and
      quality of life. We argue that personality affects quality of life by influencing
      how people approach and react to critical life situations. In the second part, we
      address the beneficial role played by two individual difference variables in
      promoting quality of life: dispositional optimism and goal adjustment. Literature
      is reviewed demonstrating that dispositional optimism facilitates subjective well
      being and good health, mediated by a person's coping behaviors. In addition, we
      discuss studies that examine people who confront unattainable goals. The reported
      evidence supports the conclusion that individual differences in people's
      abilities to adjust to unattainable goals are associated with a good quality of
      life.

PMID- 12803315
TI  - Quality of life and end-of-life decisionmaking.
AB  - Since 1976, when the New Jersey Supreme Court decided the Karen Ann Quinlan case
      (In re Quinlan, 355 A.2d 647 (NJ), 1976 cert. denied, 429 US 922, 1976), it has
      been apparent that the concept of quality of life is fundamental to end-of-life
      decisionmaking. Yet there has been a great deal of reluctance by courts--which
      have been the primary engine of lawmaking in end-of-life matters--to use this
      concept overtly.

PMID- 12803313
TI  - The case for domains of function in quality of life assessment.
AB  - Over the past 20 years, there has been a growing interest in the inclusion of
      health-related quality of life (HRQL) measures to assess the effects of a
      condition and/or its therapies on a person's health. In response to this
      interest, methods to assess health status and HRQL have proliferated. There are
      now a number of valid and reliable instruments available for use in research
      investigations, which are the culmination of years of research with various
      populations, and reflect the target populations' perceptions of their health
      status and HRQL. In this article, we provide a definition of HRQL and its
      dimensions; describe types of HRQL instruments; discuss variations in how HRQL
      measures are scored and how these methods influence the interpretation of
      results; briefly describe utility measures; and summarize by discussing basic
      issues in the selection of HRQL instruments for research investigations.

PMID- 12803316
TI  - Melatonin and immune function: hype or hypothesis?
AB  - Outside of the tropics, the combined challenge of food shortage and low
      temperature makes winter a particularly difficult time for reproduction and
      survival. Traditionally, vertebrate physiologists interested in seasonal
      phenomena have focused on reproduction and largely ignored survival. Our goal is
      to emphasize a new dimension to the study of seasonality by shifting the focus
      from reproduction to immune function and survival. Our hypothesis is that
      mechanisms enhancing immune function have evolved that enable individuals to
      anticipate predictable seasonal challenges that may adversely affect immunity.
      Stated differently, we visualize seasonal variations in survival as the
      interaction between two factors: the suppression of immune response due to
      changing energetic conditions and an endogenous rhythm of enhancement of immune
      response that is dependent on photoperiod, clocks, and melatonin. In this
      article, we review evidence of photoperiod influences on seasonal changes in
      immune function within the context of energy allocation. Further, we also examine
      mounting evidence that the pattern of melatonin secretion, mediated by
      photoperiod, directly influences immune function.

PMID- 12803317
TI  - Effects of IL-12 and IL-23 on antigen-presenting cells at the interface between
      innate and adaptive immunity.
AB  - Recent evidence from different experimental systems has demonstrated that
      autocrine activation of antigen-presenting cells (APCs) may be important at the
      initiation of an immune response, and that a specific set of cytokines may meet
      the dual needs of activating APCs and priming and/or maintaining the antigen
      specific T-cell response. Composite factors with p40, including IL-12 (p40/p35)
      and IL-23 (p40/p19), may be two such immunoregulatory cytokines, their effects
      encompassing actions on both myeloid APCs and T cells. However, although both
      cytokines enhance the Th1 costimulatory functions of APCs, and IL-23 does induce
      IL-12 from APCs, their effects, which in part overlap, can be differentiated from
      one another. This review summarizes recent data on the actions of IL-12 and IL-23
      on dendritic cells and macrophages at the interface between innate and adaptive
      immunity.

PMID- 12803318
TI  - Immune-mediated oligodendrocyte injury in multiple sclerosis: molecular
      mechanisms and therapeutic interventions.
AB  - In this review, new insights into the immunopathogenesis of multiple sclerosis
      (MS) are discussed, with special focus on the potential mechanisms leading to
      neuroinflammation in MS--that is, the role of autoreactive T cells, infections,
      and neurodegenerative events. Oligodendrocytes are considered to be the target of
      autoimmune inflammation in the CNS of MS patients. Some important features of
      oligodendrocyte biology are discussed, together with the molecular mechanisms
      that are potentially involved in oligodendrocyte injury. These include injury
      mechanisms that might be executed by the adaptive and innate immune system, via
      cytokines and/or oligodendrocyte receptors, or as a consequence of nitrative and
      oxidative stress, and excitotoxicity. The mode of cell death of oligodendrocytes
      in MS is discussed, in addition to the mechanisms of axonal injury as observed in
      pathology- and imaging-based studies. Finally, recent progress in therapeutic
      strategies that may interfere with these pathological processes are reviewed,
      with a focus on repair strategies, such as gene therapy, antibody-mediated
      remyelination, and stem cell therapy.

PMID- 12803319
TI  - Immunological effects of thalidomide and its chemical and functional analogs.
AB  - Thalidomide has recently shown considerable promise in the treatment of a number
      of conditions, such as leprosy and cancer. Its effectiveness in the clinic has
      been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell
      costimulatory and antiangiogenic activity. Novel compounds with improved
      immunomodulatory activity and side effect profiles are also being evaluated.
      These include selective cytokine inhibitory drugs (SelCIDs), with greatly
      improved TNF-alpha inhibitory activity, and immunomodulatory drugs (IMiDs) that
      are structural analogs of thalidomide, with improved properties. A third group
      recently identified within the SelCID group, with phosphodiesterase type 4
      independent activity, is in the process of being characterized in laboratory
      studies. This review describes the emerging immunological properties of
      thalidomide, from a historical context to present-day clinical applications, most
      notably in multiple myeloma but also in other cancers, inflammatory disease, and
      HIV. We also describe the laboratory studies that have led to the
      characterization and development of SelCIDs and IMiDs into potentially clinically
      relevant drugs. Early trial data suggest that these novel immunomodulatory
      compounds may supercede thalidomide to become established therapies, particularly
      in certain cancers. Further evidence is required, however, to correlate the
      clinical efficacy of these compounds with their known immunomodulatory,
      antiangiogenic, and antitumor properties.

PMID- 12803320
TI  - Cross-presentation of antigens by dendritic cells.
AB  - T lymphocytes recognize antigen presented on the surface of antigen-presenting
      cells byMHC class I and class II molecules. Classically, MHC class I molecules
      present self- or pathogen-derived antigens that are synthesized within the cell,
      whereas exogenous antigens derived via endocytic uptake are loaded onto MHC class
      II molecules for presentation to CD4+ T cells. It is becoming increasingly clear
      that some dendritic cells are also specialized to process exogenous antigens into
      the MHC class I pathway for presentation to CD8+ T cells. This process is known
      as cross-presentation. It provides a mechanism that can drive dendritic cells to
      generate either tolerance to self-antigens or immunity to pathogens. The cells
      responsible for, and mechanisms underlying, this decision between tolerance and
      immunity via cross-presentation has become the focus of intense study to
      determine how various dendritic cell subsets effect the different outcomes.

PMID- 12803321
TI  - Transcriptional analysis of tumor-specific T-cell responses in cancer patients.
AB  - Over the last decade, tumor immunology in general and tumor immunotherapy in
      particular have made important progress. Thanks to the discovery of tumor
      associated antigens (TAA), and the consequent development of active-specific
      immunization protocols, TAA-specific T-cell responses can now be induced
      reproducibly in cancer patients. However, clinical responses directly ascribable
      to TAA-specific T cells occur only occasionally. It is not clear why TAA-specific
      T cells do not eliminate tumor cells in vivo. This paradoxical coexistence of
      antigen-bearing tumor cells and antigen-specific T cells constitutes a critical
      point of current investigation. In recent years, protein-ligand interaction-based
      methods aimed at the identification and characterization of T cells using
      antibodies (cell surface phenotyping, intracellular and secreted cytokine
      detection), or HLA-peptide multimers, have significantly improved the analysis of
      TAA-specific T cells. These methods, however, seem to have reached the limit of
      their usefulness. Transcriptional analysis may add sensitivity and resolution and
      may provide global pictures of the multifactorial requirements for an efficient
      immune response against tumors. In this review, we describe the use of molecular
      genetic methods, such as real time qRT-PCR, cDNA microarrays, and TCR repertoire
      analysis. In addition, we describe techniques for high-fidelity messenger RNA
      amplification that allow high-throughput analysis of samples obtained from
      minimal sources, such as HLA/peptide tetramer sorted antigen-specific T cells,
      laser capture dissection, or fine needle aspirates. Recent work discussed in this
      review summarizes the complementarity of transcriptional analysis as an essential
      tool that, in addition to conventional methods, may deepen and broaden the
      characterization of tumor-specific T cells.

PMID- 12803322
TI  - Variation within the human killer cell immunoglobulin-like receptor (KIR) gene
      family.
AB  - The killer cell immunoglobulin-like receptors (KIR) form a family of highly
      homologous immune receptors that regulate the response of natural killer (NK)
      cells and some T cells. The genetics of the human KIR family is reviewed in this
      article. In human populations, diversity in KIR genotype arises from variations
      in gene content and allelic polymorphism. Comparisons of 81 human KIR sequences
      reveal past events ofgene duplication and recombination, and indicate that
      individual KIR genes have diversified from the influence of natural selection.
      Comparison and compilation of population studies reveal extensive KIR genotype
      variability within human populations and among them. Genomic analysis shows the
      KIR genes to be close to each other and separated by homologous sequences that
      promote haplotype diversification through assymetric recombination. In contrast,
      homologous recombination appears favored at a unique sequence in the center of
      the KIR locus, and much haplotypic diversity can be explained by recombination
      between a limited number of gene-content motifs in the centromeric and telomeric
      halves of the locus. The importance of NK cells for early defenses against
      infection suggests that human KIR genotype diversity is the accumulated
      consequence of a history of numerous and successive selective episodes by
      different pathogens on human NK-cell responses.

PMID- 12803323
TI  - Measuring emigration of human thymocytes by T-cell receptor excision circles.
AB  - Recent advances in characterizing thymic function confirm the importance of
      thymus to T-cell diversity in the periphery of both children and adults during
      both health and disease. Lack of a marker to identify human recent thymic
      emigrants (RTEs) is the biggest hurdle to accurately characterizing and
      quantifying thymic output. T-cell receptor excision circles (TRECs) are used as
      an assay to measure RTE levels. Controversy exists, however, as to whether TREC
      concentrations reflect the number of RTEs or are mainly altered by peripheral T
      cell division and death. In this review, we first summarize recent data on the
      human thymus and RTEs. On the basis of both experimental and mathematical
      analyses, we characterize factors that influence TREC dynamics in the periphery
      and elucidate primary elements that induce a decline in TREC concentrations
      during normal aging and HIV-1 infection. Our findings suggest that T-cell
      dynamics are key to the accuracy of TREC concentrations as a useful measurement
      of human RTEs.

PMID- 12803324
TI  - Moderate ischemic mitral regurgitation and coronary artery bypass surgery: effect
      of mitral repair on clinical outcome.
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal management of moderate (grade 2-3+)
      ischemic mitral regurgitation (MR) at the time of coronary artery bypass grafting
      (CABG) remains the subject of controversy. The study aim was to determine whether
      mitral repair associated with CABG is preferable to CABG alone in patients with
      moderate ischemic MR, in terms of intermediate outcome. METHODS: Among 60
      patients with moderate ischemic MR, 30 who underwent CABG plus mitral repair were
      compared with 30 others who underwent CABG alone. All patients underwent follow
      up echocardiographic and clinical examinations between 12 and 36 months after
      surgery. The decision to repair the valve during surgery was totally at the
      surgeons' discretion. RESULTS: Preoperatively, both groups were substantially
      homogeneous. Patients who had CABG plus mitral repair had a lower NYHA functional
      class at intermediate follow up, and fewer signs and symptoms of heart failure.
      On multivariate analysis, mitral repair proved to be a protective factor for the
      development of heart failure. The preoperative size of the mitral annulus was
      seen to be a risk factor for subsequent heart failure events. At intermediate
      follow up, echocardiographic parameters were significantly better in the mitral
      repair group (left ventricular volume smaller, ejection fraction and pulmonary
      artery pressure improved). CONCLUSION: The results of this case-control study
      showed that, in a homogeneous series of patients with moderate ischemic MR,
      repair of the mitral valve at the time of CABG leads to a better clinical status
      due to an improved hemodynamic profile.

PMID- 12803325
TI  - Edge-to-edge repair for functional mitral regurgitation: an echocardiographic
      study of the hemodynamic consequences.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to characterize changes in
      mitral valve area and flow, and left ventricular (LV) size and function,
      following edge-to-edge (E-E) repair for severe functional mitral regurgitation
      (MR). The possibility that preoperative dobutamine stress echocardiography (DSE)
      might be used to predict post-repair recovery in LV function was also examined.
      METHODS: Seventeen patients underwent preoperative transthoracic echocardiography
      (TTE) and DSE, intraoperative transesophageal echocardiography, and three-month
      postoperative TTE. RESULTS: After repair, mitral valve area was reduced from 8.5
      +/- 1.9 cm2 to 3.8 +/- 0.9 cm2 by planimetry (p < 0.0001) and to 2.9 +/- 0.9 cm2
      by pressure half-time. Valve area by pressure half-time correlated with the
      planimetered area (r = +0.55), but was consistently lower (p = 0.004). Sixxteen
      of 17 patients had mean transmitral gradients <5 mmHg. Postoperative LV end
      diastolic diameter improved from 72 +/- 11 to 64 +/- 10 mm (p < 0.01), and end
      systolic diameter from 56 +/- 14 to 46 +/- 12 mm (p < 0.05). Mean ejection
      fraction improved from 25 +/- 12% before repair to 38 +/- 17% after repair (p <
      0.02) in patients with evidence of LV function improvement on DSE, but was
      unchanged (15 +/- 5% versus 17 +/- 5%, p = NS) in patients without evidence of
      improvement. Postoperatively, 13 patients had no or mild MR, and two patients had
      moderate MR. There was one perioperative death. CONCLUSION: E-E repair, in
      combination with ring annuloplasty, reduces LV cavity dimensions and functional
      MR severity, without causing significant valve stenosis. Improvement on DSE may
      predict those patients in whom EF will improve following repair.

PMID- 12803326
TI  - Decreased plasma brain natriuretic peptide levels after a successful maze
      procedure.
AB  - BACKGROUND AND AIM OF THE STUDY: Previous reports indicate that plasma levels of
      atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in
      atrial fibrillation (AF), but decrease after successful direct current (DC)
      cardioversion. Although the maze procedure is the only curative therapy for AF,
      the effects on atrial and left ventricular function remain unclear. The study aim
      was to determine whether plasma ANP and BNP levels decrease after the maze
      procedure in patients with mitral valve disease. METHODS: Twenty-seven patients
      either with (n = 23) or without (n = 4) AF underwent mitral valve surgery; of
      these patients, 13 underwent a maze procedure for chronic AF. Blood samples and
      echocardiographic data were obtained before and at one year after surgery.
      RESULTS: Ten patients with AF achieved sinus rhythm (SR) or junctional rhythm
      after the maze procedure. In patients subjected to mitral valve surgery, mean
      plasma levels of ANP and BNP were 59.8 +/- 11.9 and 139.2 +/- 53.7 pg/ml,
      respectively. ANP and BNP plasma levels fell significantly after surgery (to 32.1
      +/- 4.1 and 46.7 +/- 10.2 pg/ml, respectively; p = 0.04 and p = 0.004). In
      patients with successful maze procedure, plasma levels of BNP and left
      ventricular end-diastolic dimension (LVDd) were significantly decreased by 35.7%
      and 82.7% compared with preoperative values (BNP, 35.7 +/- 4.9% for SR versus
      83.4 +/- 9.6% for AF, p = 0.008; LVDd, 82.7 +/- 3.7% for SR versus 97.0 +/- 3.2%
      for AF, p = 0.0159). CONCLUSION: A successful maze procedure significantly
      decreased LVDd and plasma levels of BNP after surgery. These results show that
      the maze procedure is effective in improving left ventricular diastolic
      dysfunction for a mid-term period in patients with mitral valve disease.

PMID- 12803327
TI  - Alterations in left ventricular curvature and principal strains in dilated
      cardiomyopathy with functional mitral regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: Functional mitral regurgitation (FMR) is
      increasingly recognized as a left ventricular (LV) disease. Dilated
      cardiomyopathy (DCM) is commonly accompanied by FMR and reduction of LV torsion.
      Therapeutic targets for DCM include LV size reduction, altered LV shape,
      elimination of MR, and increasing LV torsion. It was hypothesized that, in
      addition to increasing LV size, DCM with FMR would alter normal LV shape and
      reduce and alter the direction of principal strains across the LV wall. This
      hypothesis was tested by measuring changes in epicardial and endocardial 2-D
      principal strains and regional radii of curvature accompanying tachycardia
      induced cardiomyopathy in ovine hearts. METHODS: Radio-opaque marker arrays were
      implanted into the left ventricle of eight sheep, including one subepicardial
      triangle and one subendocardial triangle in the anterior wall of the left
      ventricle. At one week postoperatively, biplane videofluoroscopy was used to
      determine marker dynamics. Rapid ventricular pacing was then instituted until FMR
      and signs of heart failure developed, and fluoroscopy was repeated.
      Circumferential LV radii of curvature were determined from marker triplets.
      RESULTS: DCM changed the normal epicardial oval LV cross-section to a more
      circular configuration. The endocardium maintained its normal circular shape as
      the left ventricle dilated. Deformations of the triangles from end-diastole to
      end-systole were determined, and the magnitude and direction of 2-D principal
      strains calculated. DCM was associated with decreased magnitude of both
      epicardial (-0.095 +/- 0.055 versus -0.040 +/- 0.032, p = 0.006) and endocardial
      (-0.117 +/- 0.047 versus -0.073 +/- 0.037, p = 0.023) principal strains. DCM
      reduced the angle of epicardial but not endocardial principal strain. CONCLUSION:
      DCM with FMR is associated with LV dilation, circularization of the normally oval
      equatorial circumferential LV epicardium, transmural reduction in principal
      strain, and decrease in angle of principal epicardial strain. These changes
      contribute to a reduction in the net torsional moment and may guide the
      development of reverse remodeling procedures for the dilated, failing ventricle
      with FMR.

PMID- 12803328
TI  - Mitral leaflet geometry perturbations with papillary muscle displacement and
      annular dilatation: an in-vitro study of ischemic mitral regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: Perturbations of leaflet geometry are the final
      end point through which left ventricular (LV) ischemia causes incomplete mitral
      leaflet closure and resultant mitral regurgitation (MR). Geometric
      inconsistencies observed with valvular or subvalvular structural alterations
      raise several questions. METHODS: A new in-vitro LV flexible bag model was
      developed in order to visualize and analyze leaflet geometric changes under
      simulated pathological ischemic MR conditions. RESULTS: Papillary muscle (PM)
      displacement and annular dilatation decreased leaflet coaptation length, leading
      to significant MR. Symmetrical PM displacement shifted the coaptation line
      towards the leaflet edges and created central gaps along this line. Asymmetric PM
      displacement generated diametrically uneven coaptation with a tent-shaped leaflet
      at the tethered PM side, while the leaflet bulged at the opposite side towards
      the left atrium. CONCLUSION: Leaflet geometry during systole is affected by
      subvalvular structures. Asymmetric PM displacement, which may occur in regional
      or acute myocardial infarction, induces irregular deformation of the leaflet's
      coaptation line and, as a result, MR at the tethered side. Direct visualization
      of leaflet perturbation under these simulated pathological conditions may promote
      understanding of mechanisms present in ischemic MR.

PMID- 12803329
TI  - Mitral complex lesions following vagal stimulation in rabbits: relationship
      between the direction of mitral regurgitation jet and the site of mitral complex
      lesions.
AB  - BACKGROUND AND AIM OF THE STUDY: Cervical vagal stimulation in rabbits frequently
      causes bigeminy due to premature ventricular contractions, which is followed by
      systolic murmur and mitral regurgitation (MR). Peculiar lesions of the mitral
      valves, mitral annulus and papillary muscles frequently develop within a week.
      The study aim was to identify the relationship between the direction of MR jet
      and the site of mitral complex lesions in this experimental model of MR. METHODS:
      Color Doppler echocardiography was performed on anesthetized rabbits to examine
      MR, with simultaneous electrocardiographic monitoring. The animals in which the
      MR jet following cervical vagal stimulation streamed forward or backward alone in
      the left atrium were dissected on the day of vagal stimulation (n = 11) or one
      week later (n = 14), and their mitral complex lesions examined. RESULTS: Among 11
      animals dissected on the day of vagal stimulation, six of seven in which the MR
      jet streamed backward in the left atrium showed marked bleeding only in the
      anterior mitral leaflet, and three of four in which the MR jet streamed forward
      showed marked bleeding only in the posterior mitral leaflet. Among 14 animals
      dissected one week later, eight of 10 in which the MR jet streamed backward
      showed marked lesions only in the anterior mitral leaflet or anterior papillary
      muscle, and three of four in which the MR jet streamed forward, showed marked
      lesions only in the posterior leaflet or posterior papillary muscle. CONCLUSION:
      A close relationship was detected between the direction of MR jet and the site of
      mitral complex lesion, suggesting that mitral valve prolapse might be, at least
      in part, the cause of MR.

PMID- 12803330
TI  - Gender differences in left ventricular function in patients with isolated aortic
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Hypertrophic response of the left ventricle to
      systolic overload in aortic stenosis appears to be gender-dependent. METHODS: To
      examine gender-related differences in left ventricular (LV) function in patients
      with isolated severe aortic stenosis, 145 patients (65 women, 80 men; mean age 66
      +/- 8 years; range: 50 to 89 years) with aortic valve area <0.8 cm2 who underwent
      cardiac catheterization were studied. No patient had associated myocardial,
      coronary or other valve disease; patients with diabetes mellitus and systemic
      hypertension were excluded. RESULTS: No significant differences were seen in
      aortic valve area between men and women. Neither were there any significant
      gender-related differences in LV end-systolic and end-diastolic volumes, LV end
      diastolic pressure, LV mass indexed by body surface area, LV mass:volume ratio,
      LV mass:height ratio, elastic stiffness constant, ejection fraction, pulmonary
      wedge pressure, pulmonary arteriolar resistance and preload. Women showed
      significantly higher mean transaortic gradient, LV peak systolic pressure and
      peak systolic stress, end-systolic stress:end-systolic volume ratio, heart rate
      and cardiac index. In the subgroup of patients with LV pressure >199 mmHg, the
      mass:volume ratio was increased in men compared with women; of note, the
      mass:volume ratio in women was not increased in this subgroup compared with the
      general population. LV pump function in this subgroup was normal and did not
      differ between men and women. CONCLUSION: Although no clear-cut difference in
      hemodynamic parameters was seen, there was a trend towards a less compensatory
      increase in LV mass in females.

PMID- 12803331
TI  - QT interval dispersion analysis in patients with aortic valve stenosis: a
      prospective study.
AB  - BACKGROUND AND AIM OF THE STUDY: QT interval dispersion (QTd) was analyzed in
      patients with aortic valve stenosis, and the relationship investigated between
      QTd, age, gender, hypertension, presence of significant coronary artery stenosis
      and left ventricular (LV) hypertrophy assessed by echocardiography. Results were
      also compared between survivors and patients who had cardiac arrest or died
      before, during or soon after cardiac surgery. METHODS: The group comprised 535
      consecutive patients (217 women, 318 men; mean age 59 +/- 11 years; range: 20-81
      years) with significant aortic valve stenosis before valve replacement. The
      control group comprised 35 healthy subjects (12 women, 23 men; mean age 51 +/- 11
      years; range: 28-74 years). RESULTS: Mean QTd was 29 +/- 10 ms in controls and 59
      +/- 24 ms in patients (p < 0.001). Gender had no impact on QTd. QTd was increased
      in men with significant coronary artery stenosis, and independently related
      strongly with ECG parameters (QTmax, heart rate) and weakly with age and degree
      of LV hypertrophy. In patients with cardiac arrest or those who died (n = 14),
      QTd was increased compared to that in survivors (71 +/- 22 versus 59 +/- 24 ms; p
      = 0.05), and QTd >70 ms was observed more frequently (p = 0.02; odds ratio 3.4,
      1.16-10.0). CONCLUSION: QTd is abnormally increased in two-thirds of patients
      with aortic valve stenosis, and is increased in men with concomitant coronary
      artery disease. QTd >70 ms significantly increased the risk of cardiac arrest or
      death perioperatively. QTd was only weakly related with age and degree of LV
      hypertrophy, but QTmax and heart rate had a greater impact. QT dispersion
      analysis has limited clinical value in patients with aortic stenosis.

PMID- 12803332
TI  - Pressure-volume loops in patients with aortic stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Preoperative left ventricular (LV) function is
      the strongest predictor of outcome after valve replacement for aortic stenosis
      (AS). Although pressure-volume analysis with the conductance catheter technique
      can provide detailed information on LV systolic and diastolic function, this
      technique has not yet been used in AS patients. The present study examined the
      potential use of LV function measurements using pressure-volume analysis with a
      conductance catheter during surgery for AS. METHODS: In six patients with severe
      symptomatic AS, a conductance catheter was placed under transesophageal
      echocardiographic guidance in the left ventricle via the right superior pulmonary
      vein. RESULTS: The procedure was successful in all patients and lengthened the
      duration of surgery by <30 min, but with no increase in bypass or aortic cross
      clamp times. Pressure-volume analysis showed that systolic function was normal in
      all patients (ejection fraction 42-59%, end-systolic elastance 1.6-4.5 mmHg/ml),
      while diastolic dysfunction was found in all patients (Tau 32-96 ms, LV end
      diastolic pressure 7-42 mmHg, atrial kick 25-60%). After valve replacement,
      systolic function improved, but diastolic function did not. CONCLUSION: The
      conductance catheter placed via the pulmonary vein can determine LV systolic and
      diastolic dysfunction in detail in an individual patient with AS before and after
      valve replacement. The technique may be used to extend diagnostic data from less
      invasive modalities and to determine prognosis in the individual patient.

PMID- 12803333
TI  - Plasma levels of brain natriuretic peptide in various forms of obstruction to the
      left ventricular outflow tract.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship
      between plasma concentrations of brain natriuretic peptide (BNP) and the type or
      degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The
      relationship between BNP plasma level and pressure gradient (PG) in the LVOT and
      LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in
      the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had
      aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive
      cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled
      ventricular septum. Three patients with AS showed LV systolic dysfunction
      (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak
      systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic
      arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and
      HOCM patients, there was a significant positive correlation between BNP and LVPSP
      (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without
      LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p =
      0.001), but no correlation was found between BNP and LVWth in patients with HOCM.
      In AS patients including systolic LV dysfunction, BNP was negatively correlated
      with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and
      LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is
      closely associated with severity of stenosis in patients with HOCM, but mainly
      with severity of stenosis and also degree of LV systolic dysfunction in patients
      with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed
      stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with
      uneven myocardial hypertrophy).

PMID- 12803334
TI  - Prospective study of hemodynamic performances of standard ATS and AP-ATS valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Following aortic valve replacement (AVR), a
      residual transprosthetic gradient can develop which has detrimental long-term
      effects, especially with regard to left ventricular mass regression and
      subsequent mortality. The Advanced Performance-ATS valve (AP-ATS) was developed
      to overcome this potential patient-prosthesis mismatch. In the present study, the
      early postoperative transprosthetic gradient was determined after AVR with ATS
      valves 18 to 25, to confirm the promise of superior hemodynamic performance of
      the AP series and to define respective indications. METHODS: This prospective
      study included 302 consecutive patients operated on for AVR between December 1997
      and December 2000. In all patients, body surface area (BSA), associated with mean
      transprosthetic gradient and paravalvular leaks (measured echocardiographically)
      was monitored, between the 5th and 8th postoperative days. RESULTS: A
      significantly lower mean transprosthetic gradient was found for size 22 and 24
      valves, compared with size 23 and 25 valves. Results for size 18 and 20 valves
      were in concordance with those obtained for size 22 and 24 valves. For size 23
      valves the mean gradient was significantly higher when the BSA was >1.9 m2, but
      the use of size 22 valves in these patients overcame this potential patient
      prosthesis mismatch. No patient was reoperated on for paravalvular leakage, and
      no greater degree of paravalvular leakage was found with AP-ATS than with
      Standard ATS valves. CONCLUSION: These results confirm the global good
      hemodynamic performances of Standard ATS and especially of the AP-ATS valves.
      However, the significantly lower mean gradient found in the AP-ATS valves
      recommends their use in patients with larger BSA.

PMID- 12803335
TI  - Hemodynamic performance of the Medtronic ADVANTAGE prosthetic heart valve in the
      aortic position: echocardiographic evaluation at one year.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the
      echocardiographic Doppler-derived hemodynamic results at one-year follow up at a
      single center for patients receiving the Medtronic ADVANTAGE aortic prosthetic
      heart valve. This study was part of a multi-center, prospective clinical
      evaluation of the ADVANTAGE bileaflet mechanical heart valve. METHODS:
      Echocardiographic data were obtained one year postoperatively from 40 patients
      who underwent aortic valve replacement between November 1999 and March 2000. Data
      collected were in accordance with the Food and Drug Administration guidelines for
      clinical trials. RESULTS: The in-vivo mean pressure gradients for valves
      implanted in the aortic position ranged from 11.2 mmHg for size 21 valves to 6.1
      mmHg for size 29 valves, and the corresponding in-vivo effective orifice area
      ranged from 1.5 to 3.6 cm2. CONCLUSION: Early results of the study showed
      hemodynamic performance of the ADVANTAGE aortic valve to be comparable with that
      of other bileaflet valves in current clinical use.

PMID- 12803336
TI  - The Mosaic bioprosthesis in the aortic position: seven years' results.
AB  - BACKGROUND AND AIM OF THE STUDY: The Mosaic bioprosthesis is a stented porcine
      aortic valve, which combines glutaraldehyde fixation with zero-pressure and root
      pressure techniques and anti-mineralization treatment with amino-oleic acid for
      improved hemodynamics and tissue durability. The study aim was to collect
      intermediate-term data of the Mosaic bioprosthesis in the aortic position, the
      first device having been implanted in February 1994 at the authors' institution.
      METHODS: A total of 100 patients (49 females, 51 males) underwent aortic valve
      replacement with the Mosaic bioprosthesis between February 1994 and May 1999.
      Mean age at implant was 73.4 +/- 7.3 years. Concomitant procedures were performed
      in 40.0% of cases. Patients were followed up within 30 days postoperatively,
      after six months, and at annual intervals thereafter. Mean follow up was 3.8
      years (range: 0.1-7.1 years); total follow up was 383.1 patient-years (pt-yr) and
      100% complete. RESULTS: Early mortality (< or = 30 days) was 3.0%; late mortality
      was 4.6%/pt-yr, including a valve-related mortality of 0.6%/pt-yr. Freedom from
      event at seven years was 96.8 +/- 1.8% for thromboembolic events, 97.2 +/- 2.0%
      for thrombosed bioprosthesis, 96.6 +/- 2.6% for structural valve deterioration,
      98.2 +/- 1.8% for nonstructural dysfunction, 95.9 +/- 2.0% for anti
      thromboembolic hemorrhage, 98.9 +/- 1.1% for endocarditis, and 93.9 +/- 3.2% for
      reoperation/explant. After one year, the mean systolic pressure gradient was 15.3
      +/- 6.7, 14.5 +/- 5.7, 12.7 +/- 4.1 and 12.9 +/- 4.8 mmHg for 21, 23, 25 and 27
      mm valves respectively; the effective orifice area (EOA) was 1.4 +/- 0.4, 1.7 +/-
      0.4, 1.8 +/- 0.4 and 2.6 +/- 0.4 cm2 for 21, 23, 25 and 27 mm valves
      respectively; and the EOA index was 0.8 +/- 0.3, 0.9 +/- 0.2, 0.9 +/- 0.2 and 1.3
      +/- 0.1 cm2/m2 respectively. The mean left ventricular mass index was decreased
      significantly, from 159.7 +/- 56.8 g/m2 to 137.3 +/- 40.8 g/m2, for all valve
      sizes after one year. CONCLUSION: Clinical and hemodynamic performance of the
      Mosaic bioprosthesis was highly satisfactory during the first seven years after
      clinical introduction.

PMID- 12803338
TI  - Pregnancy after mechanical mitral valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Forty-six pregnancies among 32 patients after
      mitral valve replacement (MVR) were reviewed. Prosthetic valve-related
      complications, and outcome of pregnancy including feto-maternal mortality and
      morbidity for different anticoagulation regimens are presented and discussed.
      METHODS: Among 521 women of fertile age undergoing MVR with a St. Jude Medical
      mechanical prosthesis, 32 patients developed a total of 46 pregnancies. Average
      patient follow up was 5 +/- 4 years (range: 10 months-17 years); total follow up
      was 155 patient years (pt-yr). Follow up commenced at onset of the first
      pregnancy. RESULTS: Ten-year Kaplan-Meier survival estimate was 94 +/- 6%; 10
      year freedom from valve-related events was 33 +/- 14%. Rates for embolism,
      anticoagulation-related bleeding and mechanical valve thrombosis were 4.5%, 3.2%
      and 2.6% per pt-yr, respectively. Among 30 patients receiving uninterrupted low
      dose oral warfarin plus aspirin throughout pregnancy, three had normal
      deliveries, two had premature births, one had a low birth weight, seven had
      spontaneous abortions, and 17 had therapeutic abortions. By contrast, among eight
      patients who discontinued anticoagulation despite medical advice, seven had
      normal-term deliveries without thromboembolic complications, and spontaneous
      abortion occurred in one patient. Of the five women taking low molecular-weight
      heparin regimen, three had normal deliveries, one had a premature birth, and one
      an abortion. Two patients taking warfarin replaced by heparin in the first
      trimester and in the last two weeks, had term deliveries. One of these women
      developed left atrial thrombus in the third trimester while receiving heparin;
      after switching back to warfarin, the thrombus dissolved spontaneously. Another
      patient on heparin throughout the gestation had an uneventful gestation period
      that resulted in term delivery. There were four cases of prosthetic valve
      thrombosis during the postpartum period; all of these developed in women who
      ceased anticoagulation during pregnancy. CONCLUSION: There were no congenital
      malformations or maternal mortality/morbidity during pregnancy in this series of
      20 live births, probably due to the low-dose anticoagulation regimen used.
      However, anticoagulation cessation was associated with a high prosthetic valve
      thrombosis rate in the postpartum period, even when a new-generation prosthetic
      valve of unique design and expected low thrombogenicity was implanted.

PMID- 12803337
TI  - Reduction of mechanical heart valve thrombosis through a clinical audit.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves implanted
      at four cardiothoracic centers were followed up in a hospital in Eastern India.
      Despite successful surgery and regular hospital visits, long-term survival was
      compromised by anticoagulation-related complications. METHODS: Systematic
      analysis revealed under-anticoagulation in most patients. Thrombosis risk in 80
      patients on regular follow up from 1989 to 1997 was 8.68 per 100 patient years
      (pt-yr). The incidence of both thrombotic and bleeding complications was reported
      as less than two per 100 pt-yr, when prothrombin time was consistently in the
      range of INR 2.5 to 3.9. In targeting this low event rate, impediments to optimum
      anticoagulation in the local set-up were identified. International Normalized
      Ratio (INR) was introduced to report prothrombin time (PT). Patients and doctors
      were educated about drug and diet interactions with oral anticoagulants (OAC) and
      the early features of valve thrombosis. Treatment protocols were evolved. The
      impact of the remedial measures was studied in 81 patients (64 old, 17 new) over
      a total of 254 pt-yr of follow up, from 1998 to 2001. RESULTS: Thrombosis risk
      was reduced from 8.68 to 5.12 per 100 pt-yr, while non-fatal bleeding events
      increased from 0.28 to 1.96 per 100 pt-yr. Due to early recognition of occlusive
      prosthetic valve thrombosis and institution of fibrinolytic therapy, fatal events
      were reduced from 3.8 per 100 pt-yr to none for four consecutive years
      (statistically significant at 99% CI). CONCLUSION: The clinical audit proved to
      be a valuable tool for understanding the problems in health care delivery, and
      bringing about improvement.

PMID- 12803339
TI  - Thrombolytic treatment of right atrial thrombus in Behcet's disease under
      guidance of serial transesophageal echocardiography.
AB  - The case is presented of a 26-year-old man with Behcet's disease in whom a large
      and highly mobile right atrial thrombus was detected. Gradual lysis was achieved
      after two successive infusions of 1,500,000 units of streptokinase guided by
      serial transthoracic and transesophageal echocardiography.

PMID- 12803341
TI  - Bioprosthetic tissue calcification: influence of blood contact and arterial
      pressure. an experimental study in rats and sheep.
AB  - BACKGROUND AND AIM OF THE STUDY: Several animal models are currently used to
      study bioprosthetic tissue calcification. The study aim was to evaluate the
      influence of species and environmental factors (blood contact and arterial
      pressure) on valve tissue mineralization. METHODS: Glutaraldehyde-fixed porcine
      cusps and aortic wall samples were implanted subcutaneously in rats (n = 6) and
      sheep (n = 18). In sheep, similar samples were also implanted into the jugular
      vein (blood contact) and carotid artery (blood contact and arterial pressure).
      Tissue was explanted at intervals up to three months and evaluated
      macroscopically, and by X-radiography, light and electron microscopy and calcium
      content measurement. RESULTS: After eight weeks in the subcutaneous position,
      glutaraldehyde-fixed cusps were severely calcified in rats, but not in sheep
      (78.6 +/- 28.3 and 0.3 +/- 0.5 microg Ca/mg, respectively; p <0.001). Aortic wall
      samples were calcified in both species, but less in sheep (p <0.001). In sheep,
      blood contact without arterial pressure (venous implants) significantly increased
      the calcification of cusp and even more of aortic wall tissue. Arterial pressure
      had no effect on calcification of aortic wall tissue. CONCLUSION: Major inter
      species inconsistencies were found in valve tissue calcification after
      subcutaneous implantation. In sheep, blood contact increased tissue calcification
      significantly, mainly in aortic wall samples. Arterial pressure did not enhance
      mineralization of aortic wall tissue.

PMID- 12803340
TI  - Aortic valve allograft structural deterioration is associated with a subset of
      antibodies to human leukocyte antigens.
AB  - BACKGROUND AND AIM OF THE STUDY: The association between aortic valve allograft
      dysfunction in patients with long-term follow up and human leukocyte class 2
      antigen donor/recipient mismatch suggests that elements of the anti-donor immune
      response penetrate and damage the aortic valve allograft. An aortic valve
      allograft recipient cohort was studied to determine whether presence of recipient
      antibodies to donor human leukocyte class 1 or 2 antigen was associated with
      shorter time to aortic valve allograft dysfunction. METHODS: Both donor and
      recipient human leukocyte antigen (HLA) type, HLA antibody information and
      echocardiography data were available for 148 recipients of cryopreserved aortic
      valve allografts between 1986 and 1998. Structural deterioration of the aortic
      valve allograft was defined as at least moderate aortic stenosis or regurgitation
      by echocardiography. Recipient sera were assayed for anti-HLA (class 1 and 2)
      antibodies using three assays: complement-dependent cytotoxicity (CDC) on T- and
      B-lymphocyte panels (CDC PRA); flow cytometry using HLA-coated beads (Flow PRA);
      and an ELISA using HLA-coated microwells. The donor specificity of anti-class 1
      and 2 HLA antibodies was determined on T- and B-cell panels using CDC.
      Associations between the results of the three assays and donor-specific class 1
      and 2 antibodies and time to structural deterioration were analyzed using Kaplan
      Meier curves of freedom from structural deterioration. Cox proportional-hazards
      were used to determine independent predictors of time to structural
      deterioration. RESULTS: Patients highly positive for HLA class 2 antibodies using
      an ELISA had a significant association (p = 0.007) with shorter time to aortic
      valve allograft structural deterioration using both a log rank test and Cox
      proportional-hazards analysis. Patients (n = 15) with donor-specific antibodies
      to class 2 antigen (DR antigens) had significantly more structural deterioration
      (p = 0.035) than those without specific antibodies. CONCLUSION: The association
      between aortic valve allograft structural deterioration and high titer human
      leukocyte class 2 antigen antibodies, a subset detected by ELISA adds further
      information about the link between HLA class 2 mismatch and structural
      deterioration. Further studies are needed to confirm the importance of class 2
      antibodies on outcome, and to determine by which method these antibodies should
      be detected. Potential recipients with pre-existing antibodies of these specific
      types might be expected to sustain accelerated allograft damage.

PMID- 12803342
TI  - Paravalvular leaks around prosthetic valves implanted in the mitral position:
      technical refinements of the ovine model.
AB  - BACKGROUND AND AIM OF THE STUDY: Currently, the sheep model is preferred for
      preclinical in-vivo evaluation of prosthetic heart valves implanted in the mitral
      position. In sheep, the anatomy and tissue characteristics in, and around, the
      native mitral valve's posterior commissure (12:00-3:00 quadrant) makes valve
      implantation technically challenging. As the majority of non-infectious
      paravalvular leaks occurred in this quadrant, the surgical technique was modified
      to offer greater exposure of the annulus in this region and permit more accurate
      placement of sutures. METHODS: A total of 223 valve implantations (138
      bioprostheses, 85 mechanical valves) performed between 1991 and 1998 using the
      sheep model was retrospectively reviewed. No evidence of endocarditis was found,
      indicating that etiology of the leaks was due to surgical technique. The
      incidence of paravalvular leak in the 12:00-3:00 quadrant was compared with that
      in all other quadrants, both before and after the surgical technique change.
      RESULTS: The incidence of paravalvular leak was 33% (28/85) for mechanical valves
      and 13.8% (19/138) for bioprosthetic valves. Leaks in the 12:00-3:00 quadrant
      accounted for 82% (14/17) of those occurring before the surgery change, and only
      43% (13/30) afterwards. Before the change, the incidence of paravalvular leak was
      20.3% (14/69) in the 12:00-3:00 position, and 4.3% (3/69) in the non-12:00-3:00
      quadrants. After the change, incidence in the 12:00-3:00 position fell to 8.4%
      (13/154; p < 0.05), but that in other quadrants was not significantly affected.
      Analysis by valve type showed that leak incidence in the 12:00-3:00 quadrant fell
      from 20.3% (12/59) to 3.8% (3/79) in the bioprosthesis group (p < 0.05), and from
      20.0% (2/10) to 13.3% (10/75) in the mechanical valve group (p = 0.56). In all
      other quadrants there was no statistically significant change in either groups.
      CONCLUSION: Technical refinement of surgery has led to a reduced incidence of
      paravalvular leak in the 12:00-3:00 quadrant, thereby providing a standard by
      which to compare prostheses implanted in the mitral position. These data should
      also assist in improving prosthetic heart valve design by enabling device-related
      complications to be distinguished from model-related complications.

PMID- 12803343
TI  - Bubble formation on St. Jude Medical mechanical heart valves: an in-vitro study.
AB  - BACKGROUND AND AIM OF THE STUDY: Bubble formation in blood, which has been
      observed during valve closure in patients with mechanical heart valves (MHVs),
      raises concern because of cognitive changes and potential activation of blood
      elements associated with thromboembolic phenomena. Bubble formation in the
      vicinity of MHVs has been described previously; the present in-vitro study was
      undertaken to quantitate bubbles leaving the heart and entering the systemic
      circulation, and to gain a closer perspective of this phenomenon and its
      potential clinical implications. METHODS: Experiments were performed in a left
      heart pulsed flow simulator with 29 mm mitral and 23 mm aortic St. Jude Medical
      MHVs; mitral and aortic bioprosthetic valves were used as controls. De-aerated
      water was pumped through the left heart pulsed flow simulator at a fixed rate of
      70 beats/min and at different cardiac outputs. Bubble numbers and sizes were
      monitored photographically at the simulator exit. RESULTS: Numbers of bubbles per
      frame generated in MHVs in the mitral position ranged from 8 to 14 at cardiac
      outputs of 3 to 6.5 1/min; this corresponded to gas volumetric flow rates of 330
      to 830 mm3/min. The number of bubbles per frame for the aortic MHV was 3 to 7,
      reflecting the less severe flow conditions and milder valve closure impact. The
      diameter of bubbles generated by the mitral valve was almost uniform (0.45 mm),
      while bubble diameters in the aortic valve ranged from 0.36 to 0.69 mm.
      CONCLUSION: Bubble formation was found to be an inherent flaw of the present
      generation of MHVs, and this problem should be addressed in future valve designs.

PMID- 12803345
TI  - Questioning practices in health care research: the contribution of social surveys
      to the creation of knowledge.

PMID- 12803344
TI  - Endocarditis due to Peptostreptococcus anaerobius: case report and literature
      review of peptostreptococcal endocarditis.
AB  - Infective endocarditis caused by anaerobic streptococci occurs rarely, and only
      five cases have been described in detail, with two additional cases mentioned in
      a review of anaerobic infective arthritis. All have resulted from infection
      caused by peptostreptococci. Another case of anaerobic gram-positive endocarditis
      caused by Peptostreptococcus anaerobius has recently been encountered. The
      patient was successfully treated with a beta-lactam for six weeks, plus
      gentamicin (to which the organism was resistant in vitro) for two weeks. In
      reviewing these six cases, all but one involved a prosthetic valve, and in three
      instances the organism was isolated only from the infected valve. In four of six
      patients the aortic valve was involved, and five of the six survived with
      appropriate antimicrobial therapy. Embolic phenomena were confirmed in only one
      patient, who also manifested the only non-diagnostic echocardiogram.

PMID- 12803346
TI  - Survival of hemodialysis patients: modeling differences in risk of dialysis
      centers.
AB  - OBJECTIVE: Dialysis is the most common renal replacement therapy for patients
      with end stage renal disease. This paper considers survival of dialysis patients,
      aiming to assess quality of renal replacement therapy at dialysis centers in Rio
      de Janeiro, Brazil, and to investigate differences in survival between health
      facilities. METHODS: A Cox proportional hazards model, allowing for time-varying
      covariates and prevalent data, was the basic method used to analyze the survival
      of 11,579 patients on hemodialysis in 67 health facilities in Rio de Janeiro
      State from January 1998 until August 2001, using data obtained from routine
      information systems. A frailty random effects model was applied to investigate
      differences in mortality between health centers not explained by measured
      characteristics. RESULTS: The individual variables associated with the outcome
      were age and underlying disease, with diabetes being the main isolated risk
      factor. Considering covariates of the health unit, two factors were associated
      with performance: bigger units had on average better survival times than smaller
      ones and units which offered cyclic peritoneal dialysis performed less well than
      those that did not. There were significant frailty effects among centers, with
      relative risks varying between 0.24 and 3.15, and an estimated variance of 0.43.
      CONCLUSIONS: Routine assessment based on health registries of the outcome of any
      high technology medical treatment is extremely important in maintaining quality
      of care and in estimating the impact of changes in therapies, units, and patient
      profiles. The frailty model allowed estimation of variation in risk between
      centers not attributable to any measured covariates. This can be used to guide
      more specific investigation and changes in health policies related to renal
      transplant therapies.

PMID- 12803348
TI  - Common types of medication errors on long-term psychiatric care units.
AB  - OBJECTIVE: This multi-center study identified the most frequent types of
      medication errors in long-term psychiatric care hospitals. SETTING: Japan. DESIGN
      AND STUDY PARTICIPANTS: We asked 132 units in 44 Japanese psychiatric hospitals
      to introduce an in-patient incident reporting system on potential adverse drug
      events (PADEs) for the period 1 October to 30 November 2000. We analyzed types of
      PADE, outcomes, and characteristics of patients, staff, and units. RESULTS: We
      received 221 PADE incident reports from 85 units of 44 hospitals. One-quarter
      (24.9%) of the incidents were intercepted before reaching patients. The frequency
      of monitoring of the patients by clinical staff in response to medication errors
      increased by 8.1%. Wrong drug administration, i.e. giving a drug to a patient
      that was not the drug prescribed for that patient, was the most common type of
      incident (35.7%). Logistic regression analysis revealed that wrong drug
      administration occurred more frequently on units with either fewer registered
      nurses, or two or more patients with the same (or similar) name staying on the
      same unit. Incident reporters evaluated wrong drug administration as being
      potentially more serious than the other types of medication error. Wrong drug
      administration was seen more frequently in units with no patient name printed on
      medication drug pouches. CONCLUSIONS: Wrong drug administration was the most
      common type of PADE, and may result in more serious consequences than others.
      Even a simple organizational quality improvement effort, in which printed
      patients' names are placed on the drug pouch (not only with each prescription but
      with each drug administration), could reduce risk to patients from adverse
      outcomes due to medication errors.

PMID- 12803349
TI  - Indicators of quality of in-patient psychiatric treatment: the patients' view.
AB  - OBJECTIVES: The object of this study was to find out from psychiatric in-patients
      which aspects of care and treatment they considered important and how satisfied
      they were with these. DESIGN: One hundred and ninety-four in-patients were asked
      to rate the importance of, and their satisfaction with, 22 different aspects of
      in-patient care and treatment. The questionnaire, developed for the purpose of
      the study after a pilot phase including professional care givers and patients,
      contained 92 items and was returned by 52% of all discharged patients from the
      Psychiatric university hospital during a 3-month period. RESULTS: Patients made a
      clear distinction between aspects of treatment they considered important and
      aspects they were satisfied with. Ranked of highest importance were various
      therapeutic relationships, and respect for their rights and privileges. They were
      satisfied with their relationships with clinical staff but dissatisfied with
      medication. CONCLUSION: A well differentiated assessment of importance and
      satisfaction has implications for the evaluation of the quality of psychiatric
      care, for specific methods of treatment, and for the improvement of in-patient
      psychiatric care.

PMID- 12803347
TI  - Validation and application of an instrument for measuring patient relatives'
      perception of quality of geriatric care.
AB  - OBJECTIVE: To test and validate a questionnaire concerning patient relatives'
      perception of the quality of geriatric care. DESIGN: Three anonymous
      questionnaire studies. SETTINGS: A community-based geriatric care organization
      and a university hospital in Sweden. STUDY PARTICIPANTS: Three hundred and
      eighteen relatives of patients within the geriatric care organization and 38
      relatives of patients at the university hospital. MAIN OUTCOME MEASURES: A
      questionnaire composed of eight quality of care indices and an overall quality
      rating. Reliability and validity estimates were compared between the results from
      the three surveys. RESULTS: Internal reliability estimates for all indices were
      >0.65 and consistent over time. Inter-index correlations were >0.60 between
      certain indices, indicating some overlap. Second order factor analysis resulted
      in three distinct index groupings: personnel, relative's role, and care content.
      These three dimensions summarize relatives' perceptions of the quality of
      geriatric care. CONCLUSIONS: There is a need for a confidential patient
      relatives' questionnaire in geriatric care. The results revealed good
      questionnaire reliability and validity. The questionnaire needs to be tested in
      larger, independent samples in order to validate the indices further.

PMID- 12803350
TI  - Progress in the implementation of Quality Management in Dutch health care: 1995
      2000.
AB  - OBJECTIVES: Policymakers and researchers in all countries like to know whether
      the implementation of Quality Management (QM) in health care is proceeding
      satisfactorily. Longitudinal surveys can reveal whether sufficient progress is
      being made. The main objective of the study was to investigate the progress in QM
      in Dutch health care organizations during the period 1995-2000. A second
      objective was to explore whether the progress in QM was related to subsectors of
      care and/or to cultural characteristics of health care organizations. DESIGN AND
      PARTICIPANTS: The study has a descriptive longitudinal design, based on repeat
      measurements in 1995 and 2000. Empirical data about QM activities in health care
      organizations were gathered using a questionnaire. The analyses are based on data
      from the 474 health care organizations that participated in the study in 1995 and
      2000. SETTING: Participants in the study were organizations from all subsectors
      of health care, including providers of home care, nursing homes, hospitals, and
      other care sectors. MAIN OUTCOME MEASURES: Outcome measures are 46 distinct QM
      activities, which were listed in the questionnaire. RESULTS: Two-thirds of the
      organizations had made progress in the implementation of QM activities. A mean of
      25 QM activities per organization was found in 2000 compared with 20 in 1995.
      More care providers had set up a client council and had carried out patient
      satisfaction surveys. Home care organizations had made twice as much progress as
      many other health care organizations. However, nearly one-third of the health
      care organizations showed a decline in QM activities. Patient organizations were
      less often involved in the development of quality criteria and protocols.
      Progress in QM was weakly related to the dedicated and flexible attitude of
      employees and a non-hierarchical decision-making structure. CONCLUSION: The study
      demonstrates that the implementation of QM activities can be monitored at the
      national level and that differences between subsectors of care can be assessed.
      The decline in QM activities in one-third of the organizations needs to be
      researched further.

PMID- 12803351
TI  - Assessing residents' prescribing behavior in renal impairment.
AB  - OBJECTIVE: Although fitting orders to renal function avoids overdosage and
      therefore iatrogenic risk, dosage adjustment is rarely made. The objective of
      this study was to assess residents' prescribing behavior in renal impairment,
      through a standardized simulated clinical setting. METHOD: This criterion
      referenced study was carried out in a French teaching hospital. The hospital had
      118 residents; 71 of them were asked to complete a questionnaire including four
      vignettes, simulating drug prescription in four 'patients' with various degrees
      of renal impairment (16 orders). The patients had an order of gentamicin sulfate,
      diclofenac sodium, and amlodipine bensylate. For each drug, the resident could
      maintain the order, discontinue the order, or change the dosage. A fourth drug,
      enalapril maleate, was to be started, with three possible dosages and the
      possibility of not prescribing it. The reference chosen for assessment was the
      Vidal dictionary, which corresponds to the Physician's Desk Reference and is the
      French reference for prescription. RESULTS: All the residents approached for the
      survey accepted the offer to complete the questionnaire. Among the 16 simulated
      orders, the median number of appropriate orders per resident was nine.
      Considering the renal function of their patients, 62% of residents wrote an
      inappropriate order for gentamicin, 42% wrote an inappropriate order for
      didofenac, and 52% wrote an inappropriate order for enalapril. Although no
      adjustment to renal function was required, 28% of the residents decreased the
      dosage of amlodipine and ordered an underdose. CONCLUSION: Considering the
      iatrogenic risk related to the lack of dosage adjustment, attention should be
      drawn to increasing residents' awareness of dosage adjustment in renal impairment
      and to providing them with better information on patients' renal function.

PMID- 12803352
TI  - Patient satisfaction with primary health care services in the United Arab
      Emirates.
AB  - OBJECTIVE: This study evaluated the suitability of a patient satisfaction
      questionnaire to survey health care consumers of traditional Arabic background.
      DESIGN: A cross-sectional survey using an Arabic language questionnaire that drew
      upon concepts of patient satisfaction measurement in Western research literature.
      All participants were interviewed once by experienced interviewers to ascertain
      their levels of satisfaction with their health care service. SETTING: Patient
      satisfaction was compared between the only resource-intensive clinic (RIC) in the
      United Arab Emirates and one resource-thrifty clinic (RTC) located in an adjacent
      suburb and serving essentially the same population. STUDY PARTICIPANTS: A random
      sample of patients attending the RIC and RTC over a 5-day period. MAIN OUTCOME
      MEASURES: Six domains of patient satisfaction were measured. RESULTS: Compared
      with the RTC (n = 125), the RIC (n = 156) scored significantly higher in
      continuity (P = 0.001), comprehensiveness (P < 0.001), health education (P =
      0.05), effectiveness (P = 0.001), and overall satisfaction (P < 0.001), while
      accessibility (P = 0.130) and humaneness (P = 0.102) were not significantly
      different. Humaneness scored the highest and continuity the lowest at both
      clinics. Older people's satisfaction was higher for comprehensiveness but
      otherwise the same as those who were younger. More highly educated people's
      satisfaction was lower for effectiveness, but otherwise the same as those who
      were less educated. Men and women had equal levels of satisfaction. CONCLUSIONS:
      The significantly higher patient satisfaction in the RIC compared with the RTC
      was a strong a priori expectation, suggesting that this satisfaction
      questionnaire is a useful quality assurance tool in this setting.

PMID- 12803353
TI  - Using standardized patients to measure professional performance of physicians.
AB  - OBJECTIVE: To determine the nature of inaccuracies likely to occur when
      standardized patients (SPs) are used to measure physician behaviour and to
      evaluate the potential impact of these inaccuracies on estimates of physician
      performance. DESIGN: Secondary analysis from a randomized controlled trial.
      SETTING: Family physicians' offices. STUDY PARTICIPANTS: Eighteen individuals,
      each portraying one of two patient scenarios, made a total of 179 visits to 92
      family physicians who were participating in a separate randomized controlled
      trial to evaluate the impact of an educational workshop on implementation of
      preventive guidelines. MAIN OUTCOME MEASURES: Accuracy of SPs' portrayal of the
      assigned scenarios and accuracy of their coding of physician performance,
      determined on the basis of audiotapes of the visits and correlated with
      indicators of physicians' preventive practices. RESULTS: Accuracy of portrayal of
      the patient scenario was 84.8% for the male SPs and 93.5% for the female SPs.
      Inaccuracies in portrayal had no impact on physician performance scores. Accuracy
      of coding of physician performance was 90.5% for the female SPs (kappa = 0.66)
      and 90.1% for the male SPs (kappa = 0.68). Coding inaccuracies occurred most
      frequently for assessment of alcohol consumption and advice against smoking.
      CONCLUSION: SPs can provide valid information about physicians' professional
      performance. However, standardization of their activities must not be taken for
      granted. It may be more difficult to obtain standardized coding for counselling
      activities, an aspect of physician visits for which SPs are particularly
      appropriate.

PMID- 12803354
TI  - Good practice in the conduct and reporting of survey research.
AB  - Survey research is sometimes regarded as an easy research approach. However, as
      with any other research approach and method, it is easy to conduct a survey of
      poor quality rather than one of high quality and real value. This paper provides
      a checklist of good practice in the conduct and reporting of survey research. Its
      purpose is to assist the novice researcher to produce survey work to a high
      standard, meaning a standard at which the results will be regarded as credible.
      The paper first provides an overview of the approach and then guides the reader
      step-by-step through the processes of data collection, data analysis, and
      reporting. It is not intended to provide a manual of how to conduct a survey, but
      rather to identify common pitfalls and oversights to be avoided by researchers if
      their work is to be valid and credible.

PMID- 12803355
TI  - Epidemiology of occupational asthma.
AB  - Information gathered through epidemiologic studies of occupational asthma is
      useful for the establishment of prevalence or incidence data for public health
      purposes, which can be used to determine which industry or workplace requires
      assistance from preventive services. These studies address etiologic questions
      regarding exposure and host risk factors. They can establish an exposure-response
      relationship that provides scientific basis for setting environmental control
      measures. They also examine the effectiveness of preventive 5 control measures.
      In the conduct of epidemiologic studies of occupational asthma, choosing the type
      of study to answer the study question is important. Observational studies have
      predominated in studies of occupational asthma. Although these types of studies
      have provided much useful data, they are associated with the problem of the
      healthy-worker effect. In the future, use of more robust epidemiologic study
      designs should foster a greater understanding of occupational asthma.

PMID- 12803356
TI  - Differential diagnosis of occupational asthma.
AB  - Confidently establishing the diagnosis of occupational asthma (OA) is a
      complicated undertaking, because it requires that the patient's asthma symptoms
      are caused exclusively (or at least in large part) by occupational exposures.
      Asthma is a common disease, and the differential diagnosis of asthma is a
      frequently discussed subject that includes common and uncommon disorders. This
      article presents a broad characterization of OA, including the elements necessary
      to establish a diagnosis. Differential diagnosis also is discussed.

PMID- 12803357
TI  - Toxicologic considerations in workplace exposures.
AB  - The evaluation of a potential toxic exposure requires a detailed patient
      evaluation in addition to consideration of the specific chemical substance, route
      of exposure, duration and intensity of exposure, and documentation of the
      pathologic consequences.

PMID- 12803358
TI  - Occupational rhinitis.
AB  - This article aims to define occupational rhinitis, classify its various causes,
      review the steps in its diagnosis, and describe its nonpharmacologic and
      pharmacologic principles of management. Occupational rhinitis frequently coexists
      with asthma but also occurs alone. Although it does not have the same impact as
      occupational asthma, occupational rhinitis causes distress, discomfort, and work
      inefficiency. By concentrating on the patient's workplace, the clinician has an
      opportunity to practice preventive medicine: to recognize substances in the
      patient's micro- and macroenvironment that are causing the problems and then to
      intervene by altering the environment or removing the patient from the
      environment.

PMID- 12803359
TI  - Occupational allergies caused by latex.
AB  - Allergy to natural rubber latex is an important cause of occupational allergy in
      healthcare workers. Disposable medical gloves are the major reservoir of latex
      allergens, particularly powdered gloves, in healthcare delivery settings.
      Diagnosis of latex allergy requires a history of exacerbation of cutaneous,
      respiratory, ocular, or systemic signs and symptoms after exposure to natural
      rubber latex products; and evidence of sensitization by patch testing, skin
      testing, measurement of latex-specific IgE antibodies, or challenge testing.
      Optimal management of latex allergy involves education concerning cross-reacting
      allergens, reduction of cutaneous or mucosal contact with dipped rubber products,
      and minimization of exposure to latex aeroallergens in work environments.

PMID- 12803361
TI  - Occupational asthma caused by high-molecular-weight substances.
AB  - More than 250 agents that are encountered in the workplace have been shown to
      induce asthma in susceptible individuals. It is estimated that 2% to 15% of cases
      of asthma may be occupational. High-molecular-weight substances, such as plant
      and animal proteins, enzymes, and large carbohydrate molecules, can induce IgE
      mediated occupational asthma. The incidence of disease varies among industries
      and is dependent on the physiochemical properties of the agent, the level and
      duration of exposure, industrial hygiene, engineering practices, and host
      factors. Risk factors, common high-molecular-weight workplace antigens,
      diagnosis, treatment, and prognosis are discussed.

PMID- 12803360
TI  - Occupational asthma caused by exposure to low-molecular-weight chemicals.
AB  - Chemical agents cause approximately 40% of cases of occupational asthma (OA).
      Diagnosis of OA caused by chemicals relies on the demonstration of decrements in
      lung function at the workplace or during a controlled specific inhalation
      challenge to the suspect chemical agent. Evaluation of workers is accomplished
      best with a stepwise algorithmic approach and while the worker is symptomatic and
      still exposed at work. An early diagnosis followed by cessation of exposure can
      result in asthma remission and is likely to prevent progression to chronic
      disabling obstructive disease.

PMID- 12803362
TI  - Provocation studies in the diagnosis of occupational asthma.
AB  - Specific and nonspecific provocation studies, although not always essential for
      diagnosing OA, help confirm the diagnosis and identify the offending agent.
      Nonspecific bronchial challenge testing is used to detect airway
      hyperresponsiveness and to clarify the nature of the patient's symptoms.
      Pharmacologic bronchoconstrictor agents (eg, methacholine, histamine) most
      commonly are used for the challenge, but nonisotonic aerosols, exercise and
      hyperventilation also can show airway hyperresponsiveness. Nonspecific challenges
      usually are done in the laboratory, but can be done at the workplace if emergency
      equipment is available. A comparison of results obtained at and away from the
      workplace (at least 1 week apart) may be helpful in diagnosing OA. Specific
      bronchial challenge testing is considered the gold standard for OA diagnosis. It
      can be crucial in helping physicians, employers, and employees make decisions
      about continued employment, compensation, career changes, and treatment. Testing
      can pinpoint new industrial agents that cause OA, enabling dissemination of
      information on its hazards to the public and within the industry. The nature of
      the agent determines the type of protocol that is used for testing. Agents can be
      in the form of dusts, powders, aerosols, vapors gases, and animal dander.
      Exposure can be as simple as having patients simulate their work activities, or
      as complicated as using special challenge chambers with controlled environments
      and precise delivery of agents. Performing control challenges with a component
      that is separate from the test agent is essential to avoid false-positive
      results. The timing, duration, and dosing of exposure depend on the type of
      reaction that has been experienced previously, the nature of the agent, and the
      patient's baseline airway hyperresponsiveness. Serial spirometry and observation
      often are done for up to 8 hours to monitor early and late reactions. SBC testing
      should be performed in the proper medical setting in which emergency equipment
      available and should be administered only by healthcare personnel who are trained
      and experienced in the procedures. Safety of the patient is the primary
      consideration.

PMID- 12803363
TI  - Occupational contact dermatitis.
AB  - Skin reactions are common in the workplace. The skin, which constantly is exposed
      to chemicals and industrial processes, develops inflammatory reactions, most
      commonly dermatitis, which may have an allergic or irritant basis. The
      epidemiology, pathophysiology, and clinical features of common occupational
      dermatoses are discussed. Irritant, allergic, and urticarial contact reactions
      are compared, and their clinical features are outlined. Important occupational
      irritants and allergens, their sources, and the industries in which they most
      commonly are found are listed. The prognosis and therapy of these occupational
      reactions are examined.

PMID- 12803364
TI  - Indoor air quality and health does fungal contamination play a significant role?
AB  - Fungal contamination in buildings can vary greatly, and their presence in a
      dwelling does not necessarily constitute exposure. Measurement of mold spores and
      fragments varies depending on the methodology and instruments used. Meaningful
      comparison of data is rarely possible. The presence of a specific immune response
      to a fungal antigen only connotes that exposure to one or more related species
      has occurred, but not that there is a symptomatic clinical state. The response of
      individuals to indoor bioaerosols is complex and depends on age, gender, state of
      health, genetic makeup, and degree and time of bioaerosol exposure. In general,
      mold contamination in buildings is associated with incursion of water or
      moisture, which should be remedied as efficiently as possible. When disease
      occurs, it more likely is related to transient annoyance or irritational
      reactions. Allergic symptoms may be related to mold proliferation in the home
      environment. Because molds are encountered both indoors and outdoors, it is
      difficult to determine where the sensitivity initially arose and if the response
      is solely provoked by either an indoor or outdoor source. As an indoor allergen,
      mold is considered to be an infrequent participant in the induction of allergic
      disease when compared with housedust mites, animal dander, and cockroach
      allergens. Infection in healthy individuals is rare and usually is caused by an
      outdoor source. Building-related disease caused by mycotoxicosis has not been
      proved in the medical literature.

PMID- 12803365
TI  - Environmental sensitivity.
AB  - The concept of environmental sensitivity is popular among a small group of
      physicians who believe that exposure to low levels of numerous environmental
      chemicals can cause a disease with numerous symptoms but no objective physical or
      laboratory abnormalities. The condition lacks a clear definition. Numerous
      theories that have been offered to explain the condition encompass immunotoxic,
      allergic, autoimmune, neurotoxic, cytotoxic, metabolic, behavioral, psychiatric,
      iatrogenic, and sociologic mechanisms. Environmental sensitivity has many
      features in common with other controversial syndromes, such as the chronic
      fatigue syndrome. Patients with environmental sensitivity frequently are
      subjected to unproven and unnecessary diagnostic tests and therapeutic
      modalities. In spite of the lack of physical illness and absence of pathology,
      patients often experience extreme disability, because their symptoms are
      triggered by common environmental exposures. The phenomenon of environmental
      sensitivity needs to be evaluated critically using scientifically sound methods.
      The practice of clinical ecology encompasses the practices of environmental
      sensitivity and its theories. Most methods of diagnosis and treatment have been
      disproved, and the concepts underlying these theories are not scientific.
      Alternative means of diagnosis and management are presented.

PMID- 12803366
TI  - Good prospects for genetic and molecular epidemiologic studies in the European
      Journal of Epidemiology.

PMID- 12803367
TI  - Drug safety epidemiology: time for Europe to start using this instrument.

PMID- 12803368
TI  - Coffee drinking: the rationale for treating it as a potential effect modifier of
      carcinogenic exposures.
AB  - Clinical and epidemiological studies on cancer etiology seldom treat coffee
      drinking as a potential effect modifier. Yet caffeine exerts significant effects
      upon a large variety of physiologic, cellular and molecular systems. Caffeine,
      'the world's most popular drug', is also a fundamental research tool, widely used
      in clinical studies on drug metabolism, and in experimental studies on cell cycle
      checkpoints, DNA repair, and apoptosis, among many other. Caffeine can profoundly
      alter cell cycle checkpoint function and several mechanisms of DNA repair, as
      well as carcinogen metabolism. The impact of caffeine on cell cycle checkpoint
      function occurs in spite of it being nonmutagenic in traditional mutagenesis
      assays. A complex body of biologic evidence suggests that caffeine-containing
      beverages can both enhance and antagonise potentially carcinogenic exposures.
      However, most pathways leading to the ultimate effects in human beings remain
      unknown. It is unclear whether any of the hundreds of compounds contained in
      coffee and tea exert a direct and significant carcinogenic effect per se in any
      human tissue at usual conditions of use. Reasons exist to consider that coffee
      may sometimes be an indirect, positive confounder. The study of interactions
      between caffeine-containing beverages and environmental agents in well defined
      groups of healthy and diseased people could yield new insights into checkpoint
      signal transduction and other mechanisms of carcinogenesis. Information on the
      use of caffeine-containing beverages should more often be integrated in studies
      on the role of gene-environment interactions in the pathogenesis of cancer.

PMID- 12803369
TI  - Role of epidemiologic information system in sudden death prevention among
      Croatia's haemodialysis patients.
AB  - The main aim of Croatia's epidemiological information system is to enable the
      monitoring of infectious diseases as well as to enable necessary interventions.
      Its 24-hour epidemiologic alert mechanism made it possible for initial reports of
      sudden death clusters in haemodialysis units to reach epidemiologists on the
      night of 12 October 2001. The alert about the sudden deaths among haemodialysis
      patients in two hospitals has prompted us to do an epidemiological inquiry during
      that night and early the next morning. It looked at suspicions of a possible link
      between Baxter Plivadial P-15 lot 2001F075 dialyser and these deaths. As the
      suspicion was based on a small amount of data, it needed confirmation from a
      countrywide inquiry involving the other 40 haemodialysis units. A phone inquiry
      showed that 23 haemodialysis deaths occurred on 8-13 October 2001. It suggested
      that also dialyser of a different type and lot (P-18 2001B17R) should be
      incriminated. During the inquiry (October 13), all haemodialysis units were
      informed of the suspicions regarding incriminated dialysers, and of the necessity
      of temporary withdrawal of these from use. The withdrawal on 13 October of
      incriminated dialysers stopped the deaths among haemodialysis patients. No more
      such sudden deaths have been recorded since that could be linked either to the
      described period or to this clinical picture.

PMID- 12803370
TI  - Cardiovascular mortality and calcium and magnesium in drinking water: an
      ecological study in elderly people.
AB  - BACKGROUND: Previous studies found relations between cardiovascular mortality and
      minerals in drinking water, but the major works considered water hardness or
      neglected the differences between adults and elderly. Drinking water is an
      important source of calcium in the elderly particularly because of increased
      needs and decreased consumption of dairy products. METHODS: We collected
      informations about all deaths (14,311) occurring in 69 parishes of the South-West
      of France during 7 years (1990-1996). We obtained the causes of deaths from a
      special service of INSERM for each death, with age at death and sex. The exposure
      value was supplied by administrative source (DDASS) and by measurement surveys.
      We use an extra-Poisson variation model to take into account the heterogeneity of
      the population of these parishes. RESULTS: A significant relationship was
      observed between calcium and cardiovascular mortality with a RR: 0.90 for non
      cerebrovascular causes and RR: 0.86 for cerebrovascular (when calcium is higher
      than the second tercile: 94 mg/l). We found a protective effect of magnesium
      concentrations between 4 and 11 mg/l with a RR: 0.92 for non-cerebrovascular and
      RR: 0.77 for cerebrovascular mortality, as compared to concentrations lower than
      4 mg/l. CONCLUSIONS: These findings strongly suggest a potential protective dose
      effect relation between calcium in drinking water and cardiovascular causes. For
      magnesium, a U-shape effect is possible, especially for cerebrovascular
      mortality.

PMID- 12803371
TI  - Serum lipid levels in an Iranian adults population: Tehran Lipid and Glucose
      Study.
AB  - Data from 6246 participants aged 20-64 years (2339 males and 3907 females) in the
      cross-sectional phase of Tehran Lipid and Glucose Study (February 1999-May 2000)
      were used to determine distribution of serum lipid levels after 12-14 hour
      overnight fast. Mean total cholesterol (TC) concentration was 210 mg/dl. TC was
      significantly greater in females than males, 213 and 206 mg/dl, respectively (p <
      0.0001). Thirty-one percent of population had TC values between 200 and 239 and
      24% had values of 240 mg/dl or greater. Mean low-density lipoprotein cholesterol
      (LDL-C) was 129 and 135 mg/dl in males and females, respectively (p < 0.0001).
      Twenty-seven percent had LDL-C values between 130 and 159 and 23% had values 160
      mg/dl or greater. The mean triglycerides (TGs) values were 190 and 162 mg/dl for
      males and females, respectively (p < 0.0001). The mean high-density lipoprotein
      cholesterol (HDL-C) was 39 in males and 45 mg/dl in females (p < 0.0001). The
      results showed higher levels of TC, LDL-C and TGs and slightly lower HDL-C in
      Tehranian adults than other studies in the industrialized countries.

PMID- 12803372
TI  - Physical activity patterns in 50-59 year men in France and Northern Ireland.
      Associations with socio-economic status and health behaviour.
AB  - BACKGROUND: This study aimed to compare physical activity patterns and their
      associations with socio-economic status (SES) and health behaviour in two
      countries at contrasting risk for coronary heart disease (CHD). METHODS: This
      paper is a cross-sectional analysis of 7359 French and 2398 Northern Irish 50-59
      year men of the PRIME cohort. Net energy expenditure due to physical activity
      (PAE) was assessed by means of the MOSPA-Q taking high-intensity recreational
      activities into account. SES was evaluated by educational attainment and material
      conditions. Different behavioural factors (smoking, alcohol intake and healthy
      eating patterns) were considered. RESULTS: The prevalence of walking or cycling
      to work was greater in Northern Ireland (p < 10(-5)) whereas leisure PAE (p < 10(
      5)) and high-intensity leisure-time activity (p < 10(-5)) were higher in France.
      Education was positively associated with leisure-time PAE in Northern Ireland but
      negatively in France. However education in both countries and material conditions
      in France were favourably associated with the regular practice of high-intensity
      recreational activities. Alcohol consumption was positively associated with
      leisure PAE in France only (p < 10(-3)). A weak negative association was also
      observed between smoking and leisure-time activities while healthy eating
      patterns were associated with greater physical activity in both countries.
      CONCLUSIONS: Physical activity patterns and their relationships with SES and
      alcohol consumption differ in France and in Northern Ireland. Our results
      underline the need to focus on low socio-economic groups for health promotion
      but, also, to adapt strategies to promote physical activity according to cultural
      differences between countries. Our results also show that healthy behaviours tend
      to cluster in middle-aged men.

PMID- 12803373
TI  - Epidemiological survey of melanoma in the Auvergne region (France): is there an
      increased incidence in Auvergne?
AB  - To assess the efficiency of melanoma screening and prevention campaigns in the
      Auvergne region (France), cases of melanoma have been recorded since 1st June
      1998. The epidemiological follow-up of melanoma was carried out using two
      sentinel networks; one involving the pathologists, and the other, the
      dermatologists of the region. Incidence was calculated using the capture
      recapture method, by cross-matching the data supplied by both dermatologists and
      pathologists. Between June 1st 1998 and December 31st 2000, 363 cases of melanoma
      were recorded. The crude incidence rate of melanoma per 100,000 person-years was
      17.1 for all melanomas and 14.6 for invasive melanomas. These rates of incidence
      were higher than the estimated national rate of France, and were close to
      incidences found in countries of Northern Europe. This might be explained by an
      increase in screening for melanoma, by more precise estimation of the incidence
      due to the capture-recapture method, or by geographic factors (mountainous area).
      An answer may be provided by following the variation in time of incidence and
      thickness of melanomas; the increase in the number of thin (low Breslow index)
      melanomas corresponding with increased screening.

PMID- 12803374
TI  - Tuberculous meningitis in adults in Turkey: epidemiology, diagnosis, clinic and
      laboratory [corrected].
AB  - A retrospective study was performed to assess the epidemiology, diagnosis,
      clinic, and laboratory of the patients with tuberculous meningitis (TBM) in a
      multicentral study. The medical records of adult cases with TBM treated at 12
      university hospitals throughout Turkey, between 1985 and 1998 were reviewed using
      a standardized protocol. The diagnosis of TMB was established with the clinical
      and laboratory findings and/or microbiological confirmation in cerebrospinal
      fluid (CSF). The non-microbiologically confirmed cases were diagnosed with five
      diagnostic sub-criteria which CSF findings, radiological findings, extra-neural
      tuberculosis, epidemiological findings and response to antituberculous therapy. A
      total of 469 patients were included in this study. Majority of the patients were
      from Southeast Anatolia (164 patients, 35.0%) and (108 patients, 23.0%) from East
      Anatolia regions. There was a close contact with a tuberculous patient in 88 of
      341 patients (25.8%) and with a tuberculous family member in 53 of 288 patients
      (18.4%). BCG scar was positive in 161 of 392 patients (41.1%). Tuberculin skin
      test was done in 233 patients and was found to be negative in 75. Totally 115
      patients died (24.5%) of whom 23 died in 24 hour after admittance. The diagnosis
      was confirmed with clinical findings and CSF culture and/or Ziehl-Nelson staining
      in 88 patients (18.8%). Besides clinical criteria, there were three or more
      diagnostic sub-criteria in 252 cases (53.7%), two diagnostic sub-criteria in 99
      cases (21.1%), and any diagnostic sub-criteria in 30 patients (6.4%). Since TBM
      is a very critical disease, early diagnosis and treatment may reduce fatal
      outcome and morbidity.

PMID- 12803375
TI  - An epidemiological study on Verotoxin-producing Escherichia coli (VTEC) infection
      among population of northern region of Iran (Mazandaran and Golestan provinces).
AB  - Faecal samples from 3268 randomly selected inhabitants of two provinces in the
      northern region of Iran were screened to detect Verotoxin-producing Escherichia
      coli (VTEC) using colony sweep polymyxin-B extraction method. Non-sorbitol
      fermentation phenotype and slide agglutination with O157 and H7 antisera used to
      detect this serotype. We found that 0.7% of the population were infected with
      VTEC, however none of the isolates belonged to O157:H7 serotype. We also found
      that children < 6 years of age were at highest risk of infection with VTEC (p <
      0.05). Moreover, a significant association was found between the VTEC and
      diarrhoeal cases at the same age group (p < 0.001). Overall distribution of the
      VTEC isolates in the general population was found to be random, though a kind of
      clustered distribution could be noticed.

PMID- 12803377
TI  - Investigation in Central Italy of the possible association between Cryptococcus
      neoformans var. Gattii and Eucalyptus camaldulensis.
AB  - The authors present a worldwide review of isolations of Cryptococcus neoformans,
      var. neoformans and C. neoformans var. gattii from animals and vegetation,
      referring in particular to the already well-known association of the former
      variety with Eucalyptus camaldulensis. They then review the Italian situation
      relative to this association and their studies carried out in Central Italy: in
      Latina (Lazio), Pisa, Viareggio and Lake Massaciuccoli (Tuscany). From the 256 E.
      camaldulensis trees examined C. neoformans var. gattii was not isolated. An E.
      camaldulensis tree situated in the nature reserve on Lake Massaciuccoli proved to
      be positive for C. neoformans var. neoformans. This variety was isolated from the
      leaves, flowers, bark and the debris at the foot of the tree, suggesting that it
      had colonized the entire tree and that it was capable of developing not only on
      its usual habitat (bird guano, soil rich with guano) but also on Eucalyptus
      trees. The identity of the isolates was confirmed by their genomic profiles
      obtained by random amplification polymorphic DNA (RAPD) with the primer (GACA)4.
      The presence of a single genotype indicates a sole source of contamination,
      perhaps brought by a bird coming from a contaminated environment.

PMID- 12803376
TI  - Serosurvey among Mediterranean spotted fever patients of a new spotted fever
      group rickettsial strain (Bar29).
AB  - Mediterranean spotted fever is an endemic disease in Catalonia, Spain. A new
      spotted fever group (SFG) rickettsial strain (Bar29) of unknown pathogenicity for
      humans was isolated by our group, in 1996, from the dog brown tick, Rhipicephalus
      sanguineus. Interestingly, Rickettsia conorii was not isolated in this study. The
      aim of the present study was to assess the possible pathogenic role of the Bar29
      strain. To this purpose, serum samples from 15 patients with Mediterranean
      spotted fever were obtained and tested by immunofluorescence for antibodies
      against four related rickettsial strains (R. conorii, R. africae, R. massiliae,
      and Bar29). Eight of the studied sera reacted at high titers with only R. conorii
      and Bar29 antigens. For five of the eight sera, the titers against Bar29 were
      clearly higher than for R. conorii. Four of these sera were also studied by
      Western blot immunoassay to confirm a specific response. Two of these sera
      reacted with the high-molecular-mass specific proteins of Bar29 as well as with
      the low-molecular-mass region (LPS antigen) whereas their reactions with R.
      conorii were located only on bands of the LPS. This specific response would
      support the possible pathogenic role of the Bar29 strain for humans. According to
      this finding, spotted fever caused by R. conorii and rickettsial strain Bar29 may
      be present in our area. The epidemiological implications of spotted fever caused
      by R. conorii and by rickettsial strain Bar29 in the Catalonia deserve further
      studies with isolation and characterization of more rickettsial strains.

PMID- 12803379
TI  - Molecular epidemiology of Norwalk-like virus (NLV) outbreaks occurring in Kyushu
      Japan between 1988 and 1993.
AB  - In nine outbreaks that occurred in the Kyushu district between 1988 and 1993, we
      determined the nucleotide sequences of Norwalk-like virus (NLV) gene fragments
      amplified by RT-PCR and molecular-epidemiologically analyzed the NLV epidemics.
      It is known that the NLV strains isolated from nine outbreaks of acute
      gastroenteritis, were divided into five clusters consisting of two genogroups.
      Described by the year of outbreaks, the genogroup-1 (Norwalk-like virus group)
      was prevalent in 1988, 1989, and 1992, the genogroup-2 (snow mountain-like virus
      group) was detected in 1988, 1989, and 1993. Especially it was revealed that
      various strains of NLV were prevalent in the Kyushu district from 1988 to 1989.
      Epidemics of the Norwalk-like strain continued to be prevalent in 1992 (FP/7/92),
      and the strains very close to OSAP 18 continued to be prevalent in 1993 (FP/8/93,
      FP/9/93). Although the strains belonging to Norwalk virus (KY89) in the genogroup
      1 and belonging to P1B (OSAP 18) in the genogroup-2 were detected for a prolonged
      period from 1988 to 1992/ 1993, the homology in these strains was very close, and
      this study shows that a high homogeneity was conserved in these strains. It was
      revealed that various strains of NLV were prevalent in the Kyushu district from
      1988 to 1989.

PMID- 12803378
TI  - Invasive Haemophilus influenzae disease: an ecological study of sociodemographic
      risk factors before and after the introduction of Hib conjugate vaccine.
AB  - This study examines the impact of H. influenzae type b (Hib) conjugate vaccine on
      sociodemographic risk factors for invasive H. influenzae disease in the 2 years
      before and immediately after the introduction of Hib conjugate vaccine. An
      ecological study design was used and cases were identified using active
      surveillance employing several surveillance systems. The study population
      comprised all children aged < 5 years resident in the West Midlands, an English
      health region, with laboratory confirmed invasive disease 2 years before (1990
      1992) and 2 years after (1992-1994) the introduction of Hib conjugate vaccine.
      Selected sociodemographic variables derived from the UK census were obtained for
      all census enumeration districts in the region. Each variable was then ranked and
      divided into six categories. Linear associations between disease rates and
      sociodemographic variables were examined. Overall, there was a significant
      reduction in the incidence of invasive H. influenzae disease. In the pre
      conjugate vaccine era there were trends of decreasing disease incidence with
      increasing child population density (p = 0.012) and total population density (p =
      0.0023). In the post-conjugate vaccine period, total population density (p =
      0.0275) remained significant and a trend of increasing disease incidence with
      increasing population mobility (p = 0.0012) was seen. Although Hib conjugate
      vaccine has resulted in a dramatic reduction in disease incidence changes in
      sociodemographic risk factors were identified in the post-conjugate vaccine
      period, particularly population mobility. Our results may have implications for
      current and future vaccine strategies.

PMID- 12803380
TI  - Hypercholesterolemia underdiagnosis and undertreatment in psychiatric patients in
      Italy.

PMID- 12803381
TI  - Four years of monitoring for viral haemorrhagic septicaemia virus in marine
      waters around the United Kingdom.
AB  - Between 1995 and 1998, marine fish from around the coast of the UK were collected
      and samples analysed for viral haemorrhagic septicaemia virus (VHSV) using cell
      culture isolation methods. In 1997 and 1998 the samples were also analysed for
      VHSV by reverse transcription PCR (RT-PCR). A total of 1867 fish of 11 species
      were tested, but VHSV was isolated on only 1 occasion, from herring Clupea
      harengus, in 1996. However, despite VHSV not being isolated in 1997 and 1998, in
      both years samples of herring from the west and south coasts of England produced
      positive signals in the RT-PCR, and in 1997 cod from the east coast of England
      also produced positive signals in the RT-PCR. These results are believed to be
      true indications of the presence of VHSV nucleic acid in the fish. In 1997,
      birnaviruses from Serogroup B1 were isolated from herring (a previously
      unrecorded host for the virus) and cod Gadus morhua, and a birnavirus from
      Serogroup A2 was also isolated from cod. In 1998, an aquareovirus was isolated
      from haddock Melanogrammus aeglefinus, a previously unrecorded host for the
      virus.

PMID- 12803382
TI  - Experimental bacteriophage-mediated virulence in strains of Vibrio harveyi.
AB  - Vibriosis is a major disease problem in prawn aquaculture. Until now there has
      been no clear explanation why some strains of Vibrio are pathogenic, while others
      are not. This study demonstrated that the presence of the bacteriophage V.
      harveyi myovirus like (VHML) may confer virulence to V. harveyi Strain 642. This
      was demonstrated by infecting naive avirulent V. harveyi Strains 12, 20, 45 and
      645 with the bacteriophage and converting them into virulent strains. The
      previously naive strains of Vibrio infected with Bacteriophage VHML from V.
      harveyi Strain 642 demonstrated up-regulation of haemolysin, up-regulation of
      protein excretion, additional proteins which were recognised as toxic proteins
      from Strain 642 by monoclonal antibodies specific to the exotoxin sub-units, and
      a significant increase in mortality of larval Penaeus monodon. It was concluded
      that Bacteriophage VHML conferred virulence to V. harveyi Strains 12, 20, 45 and
      645 and that Bacteriophage VHML either fully or partly confers virulence in V.
      harveyi Strain 642.

PMID- 12803383
TI  - Co-infection by a yeast-like organism in Hematodinium-infected European edible
      crabs Cancer pagurus and velvet swimming crabs Necora puber from the English
      Channel.
AB  - During the winter months, edible crabs Cancer pagurus and velvet swimming crabs
      Necora puber from the English Channel can harbour infections by a Hematodinium
      sp. dinoflagellate. This parasite is responsible for a highly pathological
      condition known as 'Pink Crab Disease' (PCD) in the edible crab. In the current
      study, a high proportion (between 25 and 100%) of Hematodinium-infected edible
      and velvet swimming crabs captured from 2 sites in the English Channel also
      harboured a systemic infection by a yeast-like organism. This is the first report
      of such an infection in crabs. Budding yeast-like cells were observed
      intracellularly in circulating haemocytes and free in the host plasma. These
      cells stained positively with silver and periodic acid-Schiff (PAS) reactions.
      Despite an apparent haemocytopoenia in Hematodinium-infected crabs, haemocytic
      encapsulation of yeast-like cells was evident, while no such response was
      observed against Hematodinium sp. plasmodia. It is hypothesised that Hematodinium
      infection in these crabs may either increase the likelihood of secondary
      infections via an indirect suppression of the host immune system, or
      alternatively, decrease the likelihood of competitive growth inhibition by
      stimulating the host immune system to encapsulate and destroy secondary
      pathogens. Results are discussed with regard to the likely identity of the yeast
      like organism, and the role of secondary pathogens in the eventual mortality of
      Hematodinium-infected hosts.

PMID- 12803384
TI  - Ultrastructural details of the xenoma of Loma myrophis (phylum Microsporidia) and
      extrusion of the polar tube during autoinfection.
AB  - Xenomas of the recently described new microsporidian species Loma myrophis
      parasitizing the gut tissue of the Amazonian fish Myrophis platyrhynchus (family
      Ophichthidae) were described by light- and transmission-electron microscopy. The
      xenoma consisted of a thin fibrillar wall that surrounded a hypertrophic host
      cell cytoplasm containing numerous microsporidian developmental stages and
      spores. Several spores showed different stages of natural extrusion of the polar
      tube. Numerous longitudinal and transverse sections of the extruded polar tubes
      were observed in developing life-cycle stages (spores excepted), the nucleus of
      hypertrophic host cell, the xenoma wall and surrounding fibroblasts. The extruded
      polar tubes were projected in all directions with no preferential orientation.
      These aspects suggested that autoinfection occurred within this xenoma.

PMID- 12803385
TI  - Mikrocytos roughleyi taxonomic affiliation leads to the genus Bonamia
      (Haplosporidia).
AB  - Microcell-type parasites of oysters are associated with a complex of diseases in
      different oyster species around the world. The etiological agents are protists of
      very small size that are very difficult to characterize taxonomically. Associated
      lesions may vary according to the host species, and their occurrence may be
      related to variations in tissue structure. Lesion morphology cannot be used to
      distinguish the different agents involved. Ultrastructural observations on
      Mikrocytos roughleyi revealed similarities with Bonamia spp., particularly in
      regard to the presence of electron-dense haplosporosomes and mitochondria, whose
      absence from M. mackini also indicate that M. roughleyi and M. mackini are not
      congeneric. A partial small subunit (ssu) rRNA gene sequence of M. roughleyi was
      determined. This partial sequence, 951 nucleotides in length, has 95.2 and 98.4%
      sequence similarities with B. ostreae and B. exitiosus ssu rDNA sequences,
      respectively. Polymorphisms among the ssu rDNA sequences of B. ostreae, B.
      exitiosus and M. roughleyi allowed identification of restriction enzyme digestion
      patterns diagnostic for each species. Phylogenetic analysis based on the ssu rDNA
      data suggested that M. roughleyi belongs in the phylum Haplosporidia and that it
      is closely related to Bonamia spp. On the basis of ultrastructural and molecular
      considerations, M. roughleyi should be considered a putative member of the genus
      Bonamia.

PMID- 12803386
TI  - Molecular detection of the oyster parasite Mikrocytos mackini, and a preliminary
      phylogenetic analysis.
AB  - The protistan parasite Mikrocytos mackini, the causative agent of Denman Island
      disease in the oyster Crassostrea gigas in British Columbia, Canada, is of wide
      concern because it can infect other oyster species and because its life cycle,
      mode of transmission, and origins are unknown. PCR and fluorescent in situ
      hybridization (FISH) assays were developed for M. mackini, the PCR assay was
      validated against standard histopathological diagnosis, and a preliminary
      phylogenetic analysis of the M. mackini small-subunit ribosomal RNA gene (SSU
      rDNA) was undertaken. A PCR designed specifically not to amplify host DNA
      generated a 544 bp SSU rDNA fragment from M. mackini-infected oysters and
      enriched M. mackini cell isolates, but not from uninfected control oysters. This
      fragment was confirmed by FISH to be M. mackini SSU rDNA. A M. mackini-specific
      PCR was then designed which detected 3 to 4x more M. mackini infections in 1056
      wild oysters from Denman Island, British Columbia, than standard histopathology.
      Mikrocytos mackini prevalence estimates based on both PCR and histopathology
      increased (PCR from 4.4 to 7.4%, histopathology from 1.2 to 2.1%) when gross
      lesions were processed in addition to standard samples (i.e. transverse sections
      for histopathology, left outer palp DNA for PCR). The use of histopathology and
      tissue imprints plus PCR, and standard samples plus observed gross lesions,
      represented a 'total evidence' approach that provided the most realistic
      estimates of the true prevalence of M. mackini. Maximum parsimony and
      evolutionary distance phylogenetic analyses suggested that M. mackini may be a
      basal eukaryote, although it is not closely related to other known protistan
      taxa.

PMID- 12803387
TI  - Small subunit ribosomal DNA characterization of an unidentified
      aurantiactinomyxon form and its oligochaete host Tubifex ignotus.
AB  - In this study, the small subunit (18S) ribosomal DNA gene from an
      aurantiactinomyxon form of unknown taxonomic position (A1) and from its aquatic
      oligochaete host (Tubifex ignotus) were characterized. Molecular sequence
      information on A1 was obtained to allow comparisons of this gene with known
      sequences from known myxosporean forms, and therefore to investigate possible
      relationships between this organism and its alternate myxosporean stage. Sequence
      data for the oligochaete host, together with morphological features, will allow
      reliable identification of this species in the future. Sequence data derived from
      the 18S DNA gene and data from other related or non-related organisms were
      analyzed and used to construct a phylogenetic tree. Phylogenetic studies provided
      an insight into the taxonomic position of A1. Sequence similarities within the
      18S rDNA A1 gene and compared organisms indicated that A1 was most closely
      related to members of the sub-order Variisporina (Myxidium lieberkuehni [Ml] and
      Sphaerospora oncorhynchi [So]). Clustering of the 3 organisms in the same branch
      was well supported by high bootstrap values (81%). A1 showed higher similarities
      with sequences of Ml (approximately 80%) than with So (approximately 79%).
      Myxosporean sequence analysis indicated that phylogenetic arrangements do not
      support traditional classification based on morphological criteria of the spores,
      but rather support arrangement by tissue location. Marine actinosporeans
      Triactinomyxon sp. and Tetraspora discoidea were found to be associated with
      Platysporinid myxosporeans, supporting previous findings. In this study, 18S rDNA
      sequence data are generated for first time for the aquatic oligochaete T.
      ignotus. Phylogenetic 18S rDNA gene analyses performed with T. ignotus support
      and confirm existing morphological and molecular phylogenetic studies. Paraphyly
      of the Tubificidae family was noticed.

PMID- 12803388
TI  - Host-parasite relationships: occurrence and effect of the parasitic isopod
      Mothocya epimerica on sand smelt Atherina boyeri in the Mesolongi and Etolikon
      Lagoons (W. Greece).
AB  - The parasite-host relationship between Mothocya epimerica, Costa 1851 (Isopoda:
      Flabellifera: Cymothoidae) and sand smelt Atherina boyeri (Osteichthyes:
      Atherinidae) fish populations were studied in the Mesolongi and Etolikon Lagoons
      (W. Greece). Prevalence varied during the year from 12.5% in November to 52.5% in
      September; overall mean prevalence was 41.9%. Parasite size increased with host
      size. Infections did not have a significant effect on the host's body condition,
      such as length-weight relationship, gonadosomatic index, hepatosomatic index and
      relative condition factor. Histological damage to the host was observed on the
      gills (especially in the second and third and arches upon which the female
      parasite rests her abdomen). The physiological cost resulting from this infection
      seems to be little and probably does not constitute a serious threat for
      individual host survival.

PMID- 12803389
TI  - High variation in repetitive DNA fragment length for white spot syndrome virus
      (WSSV) isolates in Thailand.
AB  - White spot syndrome virus (WSSV) presently causes the most serious losses to
      shrimp farmers worldwide. Earlier reports of high DNA sequence homology among
      isolates from widely separated geographical regions suggested that a single virus
      was the cause. However, we have found surprisingly high variation in the number
      of 54 bp DNA repeats in ORF94 (GenBank AF369029) from 55 shrimp ponds (65 shrimp
      samples) experiencing WSSV outbreaks in Thailand in 2000 and 2002. These were
      detected by PCR amplification using primers ORF94-F and ORF94-R flanking the
      repeat region. Altogether, 12 different repeat groups were found (from 6 to 20
      repeats) with 8 repeats being most frequent (about 32%). Extracts prepared from
      individual shrimp in the same outbreak pond belonged to the same repeat group
      while those collected at the same time from separate WSSV outbreak ponds, or from
      the same ponds at different times, usually belonged to different repeat groups.
      This suggested that different outbreaks were caused by different WSSV isolates.
      In contrast to the highly variable numbers of repeats, sequence variation within
      the repeat region was confined to either T or G at Position 36. These variations
      may be useful for epidemiological studies on the local and global movement of
      WSSV, since there is high variation in the number of repeats (good for local
      studies) but little sequence change (good for global studies).

PMID- 12803390
TI  - Infection by Parvicapsula sp. (Myxozoa) is associated with mortality in sea-caged
      Atlantic salmon Salmo salar in northern Norway.
AB  - In March 2002, 3 seawater farms in northern Norway experienced high mortality
      among Atlantic salmon postsmolts. A myxosporean parasite assigned to the genus
      Parvicapsula was detected in the pseudobranchs of diseased fish, and extensive
      destruction of this organ was observed. The parasite was also found in the gills,
      liver and kidney of some fish. Based on host species, spore morphology, and the
      unusual site preference of the parasite, it is likely that it represents a
      hitherto undescribed species. The diseased fish had been transferred to seawater
      in September 2001, and it is believed that the infection took place shortly after
      exposure to seawater. The source of infection is unknown.

PMID- 12803391
TI  - A dramatic approach to management: Shakespeare, Stratford and SPVS 2003.

PMID- 12803392
TI  - Any questions?

PMID- 12803393
TI  - Systemic uptake of buprenorphine by cats after oral mucosal administration.
AB  - The plasma concentration of buprenorphine was measured by radioimmunoassay in six
      female cats after the administration of 0.01 mg/kg (0.033 ml/kg) buprenorphine
      hydrochloride solution into the side of the cat's mouth. Blood samples were taken
      through a preplaced jugular catheter before and one, two, four, six, 10, 15, 30,
      45 and 60 minutes, and two, four, six, 12 and 24 hours after the dose was
      administered. The buprenorphine was accepted well by all the cats and did not
      cause salivation or vomiting. Its median peak plasma concentration was 7.5 ng/ml
      and was reached after 15 minutes. The pharmacokinetic data were similar to the
      pharmacokinetic data obtained after the intramuscular and intravenous
      administration of buprenorphine to cats from the same colony, suggesting that the
      mucosal route of administration should be as effective as intravenous and
      intramuscular injections. In addition, the pH of the oral cavity of 26 cats was
      measured with pH paper, and 100 cat owners were asked their preferred method of
      administering drugs to cats. The pH of the cats' mouths was between 8 and 9, and
      the technique preferred by the cat owners was the use of drops placed in the
      mouth.

PMID- 12803394
TI  - Treatment of gastric ulceration in 10 standardbred racehorses with a pectin
      lecithin complex.
AB  - The severity of the erosive and ulcerative lesions of the squamous gastric mucosa
      in 10 standardbred racehorses in training was classified according to a standard
      scoring system. Each horse was then treated orally for 30 days with 50 g/100 kg
      bodyweight daily of a pectin-lecithin complex mixed into the feed. At the end of
      the period of treatment, the gastric lesions were re-evaluated gastroscopically
      and the scores were compared with those assigned at the previous evaluation. In
      three of the horses the gastric ulcerations had healed completely, and in six
      others the lesions had improved significantly.

PMID- 12803395
TI  - Enhancement of the immune response and virological protection of calves against
      bovine herpesvirus type 1 with an inactivated gE-deleted vaccine.
AB  - Four immunisation protocols based on inactivated and attenuated commercially
      available marker vaccines for bovine herpesvirus type 1 (BHV-1) were compared.
      The first group of calves were vaccinated with an attenuated vaccine administered
      intranasally and an inactivated vaccine injected subcutaneously, four weeks
      apart; the second group were vaccinated twice with the attenuated vaccine, first
      intranasally and then intramuscularly; the third group were vaccinated twice
      subcutaneously with the inactivated vaccine; and the fourth group were vaccinated
      twice intramuscularly with the attenuated vaccine. A control group of calves were
      not vaccinated. The cellular and humoral immune responses were highest in the two
      groups which received at least one injection of the inactivated vaccine.
      Virological protection was observed in all the vaccinated groups after a
      challenge infection and reactivation by treatment with dexamethasone, but the
      calves which received one dose of the inactivated vaccine as a booster or two
      doses of the inactivated vaccine excreted significantly less of the challenge
      virus than the calves which were vaccinated only with the attenuated preparation.

PMID- 12803396
TI  - Acid-base balance in field cases of bovine babesiosis.

PMID- 12803397
TI  - In vitro fertilisation of mature canine ova.

PMID- 12803398
TI  - Urethral diverticulum in a calf with XX/XY chimerism.

PMID- 12803399
TI  - Cutaneous haemangioma in a cow.

PMID- 12803400
TI  - Oral nematode infection of tarantulas.

PMID- 12803401
TI  - Supply of POMs.

PMID- 12803402
TI  - FMD control strategies.

PMID- 12803403
TI  - Severe teat lesions in a sheep flock.

PMID- 12803404
TI  - Pain in fish.

PMID- 12803405
TI  - Global suicide rates.

PMID- 12803406
TI  - Migration status and limiting long-standing illness: a longitudinal study of
      women of childbearing age in Sweden.
AB  - BACKGROUND: Despite a number of studies focusing on the health of immigrants, our
      knowledge of the risk of limiting long-standing illness (LLSI)) in migrant women
      of reproductive age is restricted. METHODS: A simple random sample of 5037
      Swedish-born and 629 foreign-born women (aged 20-41 at the first occasion) were
      interviewed over the periods 1983-1990 and 1991-1998. The risk of LLSI was
      estimated by applying logistic regression for correlated data. RESULTS: First
      generation labour-migrant women (OR=1.86) and refugee women (OR=1.75) had an
      increased risk of LLSI compared to Swedish-born women. The risk decreased only
      marginally (OR=1.64 and 1.48, respectively) after adjustment for marital status,
      socio-economic status, feelings of insecurity and the longitudinal effect of age.
      Women without employment, with a low attained level of education, without
      children, with feelings of insecurity or poor economic resources showed a high
      risk of LLSI. Similar results were observed when second-generation women were
      compared to Swedish-born women. However, immigrant women's health did not
      deteriorate more than that of Swedish-born women. CONCLUSIONS: First- and second
      generation immigrant women of reproductive age had an increased risk of LLSI,
      compared to their Swedish counterparts. Furthermore, immigrant women's health did
      not become proportionally worse than the health of Swedish women during the 8
      year period.

PMID- 12803407
TI  - Violence against pregnant women in developing countries: review of evidence.
AB  - Domestic violence among pregnant women is a global health issue. This study
      systemically reviews the literature to estimate the prevalence of violence
      against pregnant women in developing countries. Prevalence of violence among
      pregnant women in developing countries ranges from 4% to 29%. The main risk
      factors found for abuse during pregnancy were belonging to a low-income group,
      low education in both partners, and unplanned pregnancy. Low birth as a
      consequence of violence is observed. The vulnerability of pregnant women to
      violence, and to their consequences is an alarming public health issue in
      developing countries and calls for the design and implementation of better
      preventive strategies.

PMID- 12803408
TI  - Suicide mortality in the European Union.
AB  - BACKGROUND: There are an estimated one million completed suicides per year
      worldwide. As a response to increasing concern about suicide within Europe, the
      EUROSAVE (European Review of Suicide and Violence Epidemiology) study was
      undertaken to examine recent trends in the epidemiology of suicide and self
      inflicted injury mortality in the European Union (EU). METHODS: Suicide and self
      inflicted injury mortality data for the 15 EU countries for the years 1984-1998
      were obtained from the World Health Organisation (WHO), the European Statistical
      Office of the European Commission (EUROSTAT) and national statistical agencies.
      Data were also obtained for a second group of deaths classified as 'undetermined'
      or 'other violence'. Age-standardized mortality rates were calculated and
      examined for trends over time. RESULTS: Finland had the highest suicide rate,
      while Greece had the lowest for the latest available year (1997). Age
      standardized suicide rates tended to be lowest in the Mediterranean countries.
      Significant downward linear time trends in suicide mortality were observed in
      most countries, although rates varied markedly between countries. Both Ireland
      and Spain displayed significant upward linear trends in suicide mortality.
      Portugal had the highest rate of undetermined deaths both in 1984 and 1998 while
      Greece had the lowest in both 1984 and 1997. Five countries (including Ireland
      and Spain) showed significant downward trends in deaths due to undetermined
      causes whereas Belgium and Germany showed borderline significant upward linear
      trends in deaths due to undetermined causes. CONCLUSIONS: Although suicide rates
      in most countries seem to be decreasing, the validity of the data is uncertain.
      Misclassification may contribute to the geographical and temporal variation in
      suicide rates in some EU countries but it does not explain the phenomenon. More
      detailed research comparing suicide-recording procedures and practices across the
      EU is required. In the absence of adequate EU wide data on suicide epidemiology,
      effective prevention of this distressing phenomenon is likely to remain elusive.

PMID- 12803409
TI  - Examining geographic patterns of mortality: the atlas of mortality in small areas
      in Spain (1987-1995).
AB  - BACKGROUND: Small-area mortality atlases have been demonstrated to be a useful
      tool for both showing general geographical patterns in mortality data and
      identifying specific high-risk locations. In Spain no study has so far
      systematically examined geographic patterns of small-area mortality for the main
      causes of death. This paper presents the main features, contents and potential
      uses of the Spanish Atlas of Mortality in small areas (1987-1995). METHODS:
      Population data for 2,218 small areas were drawn from the 1991 Census. Aggregated
      mortality data for 14 specific causes of death for the period 1987-1995 were
      obtained for each small area. Empirical Bayes-model-based estimates of age
      adjusted relative risk were displayed in small-area maps for each
      cause/gender/age group (0-64 or 65 and over) combination using the same range of
      values (i.e. septiles) and colour schemes. RESULTS: The 'Spanish Atlas of
      Mortality' includes multiple choropleth (area-shaded) small-area maps and graphs
      to answer different questions about the data. The atlas is divided into three
      main sections. Section 1 includes the methods and comments on the main maps.
      Section 2 presents a two-page layout for each leading cause of death by gender
      including 1) a large map with relative risk estimates, 2) a map that indicates
      high- and low-risk small areas, 3) a graph with median and interquartile range of
      relative risk estimates for 17 large regions of Spain, and 4) relative-risk maps
      for two age groups. Section 3 provides specific information on the geographical
      units of analysis, statistical methods and other supplemental maps. CONCLUSION:
      The 'Spanish Atlas of Mortality' is a useful tool for examining geographical
      patterns of mortality risk and identifying specific high-risk areas. Mortality
      patterns displayed in the atlas may have important implications for research and
      social/health policy planning purposes.

PMID- 12803410
TI  - Use of butter and cheese in 10 European countries: a case of contrasting
      educational differences.
AB  - BACKGROUND: This paper aims to analyse socioeconomic variation in the use of
      cheese and butter in Europe by reviewing existing dietary surveys. It explores
      whether socioeconomic differences in the intake of these foods follow a similar
      pattern in all countries. METHODS: An overview of available studies on
      socioeconomic differences in food habits in Europe over the period 1985-1997 was
      performed. Twenty studies from 10 countries included information on cheese and
      butter. A simple directional vote-counting method was used to register the
      association between educational level and consumption of cheese and butter
      (animal fat) for each study. FAO's food balance sheets were used to classify the
      countries according to consumption trends of these foodstuffs. RESULTS: In all
      countries higher social classes used more cheese than lower classes. The results
      for butter were less consistent. In the Nordic countries higher social classes
      used less butter than lower ones. In the other countries an opposite pattern or
      no differences could be observed. However, in countries where the use of both
      butter and animal fats could be analysed, animal fats were used more by the lower
      social classes. CONCLUSIONS: Higher and lower socioeconomic groups have different
      sources of saturated fats. Higher social classes use more cheese whereas lower
      social classes use more butter or animal fats. This can be observed especially in
      countries where the consumption of cheese is increasing and that of butter
      decreasing. Higher social classes prefer modern foods, lower classes traditional
      foods.

PMID- 12803411
TI  - Influenza vaccination in old adults in Spain.
AB  - BACKGROUND: to describe population patterns of influenza vaccination, and to
      analyse the effect of a set of demographic, socio-economic status, lifestyles,
      health status, and health services variables, on the likelihood of being
      vaccinated in the those > or = 65 years. METHODS: Cross-sectional study. From the
      1997 National Health Survey those > or = 65 years old were selected. Adjusted
      odds ratios were calculated through multiple logistic regression models,
      reporting having an influenza vaccination last season as a dependent variable.
      RESULTS: A total sample of 1148 was analysed: 51.3% of subjects reported having
      received a vaccination last year. Adjusted odds ratios showed that the risk of
      not having been vaccinated was higher for people from 65-69 years (OR: 1.70; 95%
      CI [1.32-2.19]), women (OR: 1.48; 95% CI [1.14-1.92]), residents in cities of
      more than 1 million inhabitants (OR: 1.74; 95% CI [1.12-2.70]), smokers (OR:
      1.92; 95% CI [1.24-2.96]), having high-risk chronic conditions (OR: 1.41; 95% CI
      [1.08-1.85]), and for those whose last physician visit was between 2 weeks and 6
      months ago (OR: 1.40; 95% CI [1.07-1.85]), and more than 6 months ago (OR: 2.13;
      95% CI [1.52-2.98]). CONCLUSION: Influenza vaccination levels are sub-optimal.
      Factors that have been identified as barriers to receiving this effective
      intervention are: younger age, female sex, less contact with the health care
      system, smokers, and not having high-risk chronic conditions. No effect was found
      for socio-economic status or variables related with health, functional status or
      other health-related behaviours. This study may contribute to identifying
      population groups who could be targeted for health promotion interventions aimed
      to improve their influenza vaccination uptake.

PMID- 12803412
TI  - On the use of administrative databases to support planning activities: the case
      of the evaluation of neonatal case-mix in the Emilia-Romagna region using DRG and
      APR-DRG classification systems.
AB  - There are several versions of the Diagnosis Related Group (DRG) classification
      systems that are used for case-mix analysis, utilization review, prospective
      payment, and planning applications. The objective of this study was to assess the
      adequacy of two of these DRG systems--Medicare DRG and All Patient Refined DRG-
      to classify neonatal patients. The first part of the paper contains a descriptive
      analysis that outlines the major differences between the two systems in terms of
      classification logic and variables used in the assignment process. The second
      part examines the statistical performance of each system on the basis of the
      administrative data collected in all public hospitals of the Emilia-Romagna
      region relating to neonates discharged in 1997 and 1998. The Medicare DRG are
      less developed in terms of classification structure and yield a poorer
      statistical performance in terms of reduction in variance for length of stay.
      This is important because, for specific areas, a more refined system can prove
      useful at regional level to remove systematic biases in the measurement of case
      mix due to the structural characteristics of the Medicare DRGs classification
      system.

PMID- 12803413
TI  - Analysis of some variables concerning guidelines adopted in a hospital in Milan:
      quantity, quality and physicians' attitude; which is the reciprocal influence of
      these factors?
AB  - BACKGROUND: Starting in 1998 the Italian NHS promoted the adoption of practice
      guidelines without, however, launching directions on how they should be produced
      and adopted. The aim of the current work was to explore the relationship between
      number and quality of guidelines and physicians' attitudes towards them. METHODS:
      All documents named 'guidelines' adopted after 1998 by each unit at the San Paolo
      Hospital (SPH), a 600-bed university hospital were collected. The quality of
      these guidelines was assessed according to a seven point scale looking at
      methodological quality and completeness of reporting. A 16-item questionnaire was
      delivered to all physicians of the SPH investigating barriers affecting their
      attitude towards adopting guidelines. The correlation between quantity and
      quality of guidelines and physicians' attitude was explored. RESULTS: In total,
      319 documents from 19 units were examined. The overall quality varied across
      units and was generally poor (range: 0.5-3 items satisfied per guideline). Of the
      392 physicians sampled, 301 filled in the questionnaire, and a positive attitude
      to guidelines was found. None of the relationships analysed--quantity, quality
      and attitude--turned out to be significantly associated. CONCLUSIONS: This study
      highlights contrasting results. The number of recorded documents and physicians'
      attitude indicate a vivacious interest in guidelines even if the quantitative
      production was extremely variable among units and the quality was unsatisfactory.
      This scenario may suggest a transition period in which the lack of a solid
      methodological background in the production and adoption of guidelines runs into
      the need to be compliant to a new rule.

PMID- 12803414
TI  - Early detection of psychosocial problems in adolescents: how useful is the Dutch
      short indicative questionnaire (KIVPA)?
AB  - BACKGROUND: Psychosocial problems, such as behavioural, emotional, and
      educational problems, are highly prevalent among children and adolescents. Early
      treatment may reduce these problems, if accurately identified. Validated
      questionnaires may support identification. The aim of this study is to assess the
      psychometric qualities of such a questionnaire, the Short Indicative
      Questionnaire for Psychosocial problems among Adolescents (KIVPA,) and to
      determine whether it is suitable for and adds to the early detection of
      psychosocial problems among adolescents. METHODS: Data came from a national
      sample of 1,440 Dutch adolescents, using the KIVPA, the Child Behavior Checklist
      (CBCL), and the Youth Self-Report (YSR). Of these, 1,248 provided data on all
      questionnaires (77.8%). The scale structure of the KIVPA was assessed; its
      sensitivity and specificity using CBCL, YSR and referral for psychosocial
      problems as criteria; and its contribution to detecting CBCL and YSR problems.
      RESULTS: The KIVPA is mostly uni-dimensional but the variance explained by its
      main factor is relatively low. The total KIVPA score discriminates between
      adolescents with and without problems on the three criteria. Using a clinical YSR
      total problem score as criterion, sensitivity and specificity are 0.82 and 0.85,
      respectively, at the proposed cut-off (area under the ROC curve: 0.92; 95%
      confidence interval (CI) 0.90-0.95). The odds ratio of a clinical YSR score for
      an elevated KIVPA score is 29.1 (95% CI: 14.4-59.1), although the KIVPA mainly
      covers internalizing problems. CONCLUSION: The KIVPA has added value in the early
      detection of internalizing psychosocial problems, but is not sufficiently
      efficient.

PMID- 12803415
TI  - Changes and determinants in cigarette smoking prevalence in southwestern France,
      1985-1997.
AB  - OBJECTIVE AND METHODS: Smoking trends were assessed in southwestern France for
      the period 1985-1997 using data from the MONICA population surveys conducted in
      the Toulouse region. RESULTS: Smoking prevalence decreased in men and remained
      stable in women, with the exception of age group 35-44 years (stabilization in
      men, increase in women). In both genders, prevalence of ex-smokers increased.
      Higher educational level was negatively associated with smoking in men and
      positively associated in women; in both genders, older age was negatively
      associated with smoking. CONCLUSIONS: In southwestern France, the decrease or
      stabilization in smoking prevalence is due to an increase in ex-smokers rather
      than in never smokers.

PMID- 12803416
TI  - Knowledge and attitudes of economically disadvantaged women regarding exposure to
      environmental tobacco smoke: a Michigan, USA study.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) is a global public
      health problem which is particularly acute in groups where smoking rates are
      higher than in the general population. A study was undertaken to investigate
      knowledge, attitudes and preventive efforts with regard to exposure to ETS in a
      sample of economically disadvantaged women residing in Michigan, USA. METHODS:
      Analysis-of-variance techniques were used to investigate how knowledge, attitudes
      and preventive efforts regarding exposure to ETS relate to demographic variables
      such as smoking status, ethnicity, education, employment, and income; and
      analysis-of-covariance techniques were applied to determine the degree to which
      knowledge, attitudes, age, smoking status, ethnicity, education, employment,
      income and home environment predict these women's preventive efforts regarding
      exposure to ETS. RESULTS: Generally, women with no high school diploma and women
      who were smokers were less knowledgeable about the adverse health effects of
      exposure to ETS, had worse attitudes concerning exposure to ETS and were less
      likely to take preventive steps to limit their exposure to ETS than were women
      who had more formal education or who were nonsmokers, respectively. The primary
      predictors of preventive efforts were knowledge, attitudes and smoking status.
      CONCLUSIONS: The results suggest that educational efforts focusing on increasing
      knowledge and improving attitudes regarding exposure to ETS, as well as providing
      practical strategies for limiting exposure to ETS, should be developed and
      delivered to at-risk populations.

PMID- 12803418
TI  - The physician/care provider and politics: life and society viewed from different
      angles: a cross-cultural issue.
AB  - PREAMBLE: This article is written by the "Medecin cantonal" (Chief Medical
      Officer) of the Swiss Canton of Vaud (capital city, Lausanne). Under the Swiss
      Constitution, responsibility for most health-related issues lies with the
      Cantons. The "Medecin cantonal" is the medical advisor to the health minister and
      the cantonal government. His or her traditional role concerned the organisation
      of health care delivery, such as the distribution of hospitals and licencing of
      practitioners, as well as health promotion, school health and disaster
      preparedness. However this has changed considerably in the face of health
      threats, such as HIV/AIDS and the rise in drug addiction. These bring new and
      complex challenges, and in particular bioethical concerns. In this personal view
      the author discusses his experience at this intersection between medicine, health
      care, the exercise of public authority, politics and civil society. In particular
      he reflects on how physicians and politicians have different perspectives on the
      circumstances of collective life.

PMID- 12803417
TI  - Ministerial challenges: post-conflict, post-election issues in Kosovo's health
      sector.
AB  - BACKGROUND: On 17 November 2001, less than 900 days after the end of one of the
      largest population displacements since 1945, the, Kosovo electorate voted for
      their new self-government. An Assembly was formed in 2001 and a Health Minister,
      Dr Numan Balic, appointed in March 2002. He has inherited a health service that
      still reels from many years of neglect while it struggles to implement an
      ambitious health reform programme. METHODS: An analysis of UNMIK Regulations and
      available grey literature within Kosovo has formed the basis of material for this
      article. In addition, the authors collected, by informal interview, the opinions
      of international and Kosovars actively employed within the health sector. The
      authors would wish to acknowledge the contribution of Dr Hannu Vuori, Principal
      International Officer, Ministry of Health, Kosovo for his insight and
      suggestions. RESULTS: The analysis reveals that the current health system is
      inequitable and inefficient. The health sector reforms initiated by the
      international community are desperately needed: it is purported that one-in-three
      Kosovars cannot afford to access health care when ill. However, the combined
      legacy of neglect, the current status of the health service and the new Assembly
      regulations present significant challenges to health reform. CONCLUSIONS: Under
      the gaze of the newly formed Assembly, as well as the watchful eye of the United
      Nations Interim Administrative Mission in Kosovo, the Minister will take on the
      arduous responsibility of governing the Kosovo health sector. In any context
      implementing reform is difficult, in Kosovo it may be even more so and the
      international community should not exclusively focus on other world-trouble spots
      when many challenges remain to be addressed.

PMID- 12803419
TI  - The fundamental processes in ecology: a thought experiment on extraterrestrial
      biospheres.
AB  - Ecological science is often organised as a hierarchical series of entities:
      genes, individuals, populations, species, communities, ecosystems and biosphere.
      Here, I consider an alternative process-based approach to ecology, and analyse
      the nature of the fundamental processes in ecology. These fundamental processes
      are discussed in the context of the following question: 'for any planet with
      carbon-based life, which persists over geological time scales, what are the
      minimum set of ecological processes that must be present?' I suggest that the
      following processes would be present on any such planet: energy flow, multiple
      guilds, ecological trade-offs leading to within-guild biodiversity, ecological
      hypercycles, merging of organismal and ecological physiology, carbon
      sequestration and possibly photosynthesis. Nutrient cycling is described as an
      emergent property of these fundamental processes. I discuss reasons why a
      biosphere based on a single species with no nutrient cycling is very unlikely to
      exist. I also describe the concept of 'Gaian effect'. This suggests that some
      processes will always tend to extend the lifespan of a biosphere in which they
      develop (positive Gaian effect) while others could either increase or decrease
      (negative Gaian effect) such a lifespan. These ideas are discussed in the context
      of astrobiology, ecosystem services, conservation biology and Gaia theory.

PMID- 12803420
TI  - Climatic variability and the evolution of insect freeze tolerance.
AB  - Insects may survive subzero temperatures by two general strategies: Freeze
      tolerant insects withstand the formation of internal ice, while freeze-avoiding
      insects die upon freezing. While it is widely recognized that these represent
      alternative strategies to survive low temperatures, and mechanistic understanding
      of the physical and molecular process of cold tolerance are becoming well
      elucidated, the reasons why one strategy or the other is adopted remain unclear.
      Freeze avoidance is clearly basal within the arthropod lineages, and it seems
      that freeze tolerance has evolved convergently at least six times among the
      insects (in the Blattaria, Orthoptera, Coleoptera, Hymenoptera, Diptera and
      Lepidoptera). Of the pterygote insect species whose cold-tolerance strategy has
      been reported in the literature, 29% (69 of 241 species studied) of those in the
      Northern Hemisphere, whereas 85 % (11 of 13 species) in the Southern Hemisphere
      exhibit freeze tolerance. A randomization test indicates that this predominance
      of freeze tolerance in the Southern Hemisphere is too great to be due to chance,
      and there is no evidence of a recent publication bias in favour of new reports of
      freeze-tolerant species. We conclude from this that the specific nature of cold
      insect habitats in the Southern Hemisphere, which are characterized by oceanic
      influence and climate variability must lead to strong selection in favour of
      freeze tolerance in this hemisphere. We envisage two main scenarios where it
      would prove advantageous for insects to be freeze tolerant. In the first,
      characteristic of cold continental habitats of the Northern Hemisphere, freeze
      tolerance allows insects to survive very low temperatures for long periods of
      time, and to avoid desiccation. These responses tend to be strongly seasonal, and
      insects in these habitats are only freeze tolerant for the overwintering period.
      By contrast, in mild and unpredictable environments, characteristic of habitats
      influenced by the Southern Ocean, freeze tolerance allows insects which
      habitually have ice nucleators in their guts to survive summer cold snaps, and to
      take advantage of mild winter periods without the need for extensive seasonal
      cold hardening. Thus, we conclude that the climates of the two hemispheres have
      led to the parallel evolution of freeze tolerance for very different reasons, and
      that this hemispheric difference is symptomatic of many wide-scale disparities in
      Northern and Southern ecological processes.

PMID- 12803421
TI  - Chloride ATPase pumps in nature: do they exist?
AB  - Five widely documented mechanisms for chloride transport across biological
      membranes are known: anion-coupled antiport, Na+ and H(+)-coupled symport, Cl-
      channels and an electrochemical coupling process. These transport processes for
      chloride are either secondarily active or are driven by the electrochemical
      gradient for chloride. Until recently, the evidence in favour of a primary active
      transport mechanism for chloride has been inconclusive despite numerous reports
      of cellular Cl(-)-stimulated ATPases coexisting, in the same tissue, with uphill
      ATP-dependent chloride transport. Cl(-)-stimulated ATPase activity is a
      ubiquitous property of practically all cells with the major location being of
      mitochondrial origin. It also appears that plasma membranes are sites of Cl(-)
      stimulated ATPase pump activity. Recent studies of Cl(-) -stimulated ATPase
      activity and ATP-dependent chloride transport in the same plasma membrane system,
      including liposomes, strongly suggest a mediation by the ATPase in the net
      movement of chloride up its electrochemical gradient across the plasma membrane
      structure. Contemporary evidence points to the existence of Cl(-)-ATPase pumps;
      however, these primary active transporters exist as either P-, F- or V-type
      ATPase pumps depending upon the tissue under study.

PMID- 12803422
TI  - Formation of dermal skeletal and dental tissues in fish: a comparative and
      evolutionary approach.
AB  - Osteichthyan and chondrichthyan fish present an astonishing diversity of skeletal
      and dental tissues that are often difficult to classify into the standard
      textbook categories of bone, cartilage, dentine and enamel. To address the
      question of how the tissues of the dermal skeleton evolved from the ancestral
      situation and gave rise to the diversity actually encountered, we review previous
      data on the development of a number of dermal skeletal elements (odontodes, teeth
      and dermal denticles, cranial dermal bones, postcranial dermal plates and scutes,
      elasmoid and ganoid scales, and fin rays). A comparison of developmental stages
      at the tissue level usually allows us to identify skeletogenic cell populations
      as either odontogenic or osteogenic on the basis of the place of formation of
      their dermal papillae and of the way of deposition of their tissues. Our studies
      support the evolutionary affinities (1) between odontodes, teeth and denticles,
      (2) between the ganoid scales of polypterids and the elasmoid scales of teleosts,
      and (3) to a lesser degree between the different bony elements. There is now
      ample evidence to ascertain that the tissues of the elasmoid scale are derived
      from dental and not from bony tissues. This review demonstrates the advantage
      that can be taken from developmental studies, at the tissue level, to infer
      evolutionary relationships within the dermal skeleton in chondrichthyans and
      osteichthyans.

PMID- 12803423
TI  - Early tetrapod relationships revisited.
AB  - In an attempt to investigate differences between the most widely discussed
      hypotheses of early tetrapod relationships, we assembled a new data matrix
      including 90 taxa coded for 319 cranial and postcranial characters. We have
      incorporated, where possible, original observations of numerous taxa spread
      throughout the major tetrapod clades. A stem-based (total-group) definition of
      Tetrapoda is preferred over apomorphy- and node-based (crown-group) definitions.
      This definition is operational, since it is based on a formal character analysis.
      A PAUP* search using a recently implemented version of the parsimony ratchet
      method yields 64 shortest trees. Differences between these trees concern: (1) the
      internal relationships of aistopods, the three selected species of which form a
      trichotomy; (2) the internal relationships of embolomeres, with Archeria
      crassidisca and Pholiderpeton scut collapsed in a trichotomy with a clade formed
      by Anthracosaurus russelli and Pholiderpeton attheyi; (3) the internal
      relationships of derived dissorophoids, with four amphibamid species forming an
      unresolved node with a clade consisting of micromelerpetontids and
      branchiosaurids and a clade consisting of albanerpetontids plus basal crown-group
      lissamphibians; (4) the position of albenerpetontids and Eocaecilia micropoda,
      which form an unresolved node with a trichotomy subtending Karaurus sharovi,
      Valdotriton gracilis and Triadobatrachus massinoti; (5) the branching pattern of
      derived diplocaulid nectrideans, with Batrachiderpeton reticulatum and
      Diceratosaurus brevirostris collapsed in a trichotomy with a clade formed by
      Diplocaulus magnicornis and Diploceraspis burkei. The results of the original
      parsimony run--as well as those retrieved from several other treatments of the
      data set (e.g. exclusion of postcranial and lower jaw data; character
      reweighting; reverse weighting)--indicate a deep split of early tetrapods between
      lissamphibian- and amniote-related taxa. Colosteids, Crassigyrinus, Whatcheeria
      and baphetids are progressively more crownward stem-tetrapods. Caerorhachis,
      embolomeres, gephyrostegids, Solenodonsaurus and seymouriamorphs are
      progressively more crownward stem-amniotes. Eucritta is basal to temnospondyls,
      with crown-lissamphibians nested within dissorophoids. Westlothiana is basal to
      Lepospondyli, but evidence for the monophyletic status of the latter is weak.
      Westlothiana and Lepospondyli form the sister group to diadectomorphs and crown
      group amniotes. Tuditanomorph and microbrachomorph microsaurs are successively
      more closely related to a clade including proximodistally: (1) lysorophids; (2)
      Acherontiscus as sister taxon to adelospondyls; (3) scincosaurids plus
      diplocaulids; (4) urocordylids plus aistopods. A data set employing cranial
      characters only places microsaurs on the amniote stem, but forces remaining
      lepospondyls to appear as sister group to colosteids on the tetrapod stem in
      several trees. This arrangement is not significantly worse than the tree topology
      obtained from the analysis of the complete data set. The pattern of sister group
      relationships in the crownward part of the temnospondyl-lissamphibian tree re
      emphasizes the important role of dissorophoids in the lissamphibian origin
      debate. However, no specific dissorophoid can be identified as the immediate
      sister taxon to crown-group lissamphibians. The branching sequence of various
      stem-group amniotes reveals a coherent set of internested character-state changes
      related to the acquisition of progressively more terrestrial habits in several
      Permo-Carboniferous forms.

PMID- 12803424
TI  - Electrophysiological analysis of context effects in Alzheimer's disease.
AB  - Event-related potentials elicited by semantically associated and unassociated
      word pairs embedded in congruous and semantically anomalous spoken sentences were
      recorded from patients with Alzheimer's disease (AD) and healthy older and young
      controls as a means of examining the nature, time course, and relation between
      word and sentence context effects. All groups demonstrated lexical priming in
      nonsensical sentences, but it was earlier in the young (200-600 ms) than in the
      older controls (600-800 ms), and even later in the probable AD patients (800
      1,000 ms). Moreover, processing in both the elderly and AD groups benefited
      disproportionately from a meaningful sentence context. The results do not accord
      well with either a strictly structural or a strictly functional account of the
      semantic impairments in AD.

PMID- 12803425
TI  - Facilitating acquisition and transfer of a continuous motor task in healthy older
      adults and patients with Alzheimer's disease.
AB  - This study examined the acquisition and transfer of a fine motor skill, namely
      the rotary pursuit, in 99 patients with Alzheimer's disease (AD) and 100 normal
      controls (NCs). To identify optimal learning strategies, the authors had
      participants practice the rotary pursuit under constant, blocked, random, or no
      training conditions. Transfer was assessed using speeds that were different from
      those practiced during acquisition. AD patients and NCs receiving constant
      practice outperformed their peers in the blocked and random conditions during
      acquisition. Whereas all 3 types of practice facilitated transfer in the NCs, AD
      patients only benefited from constant practice. The inability of the AD patients
      to benefit from variable practice suggests that these individuals may have
      difficulty accessing and/or forming motor schemas.

PMID- 12803426
TI  - Redundancy gain in the acallosal brain.
AB  - The authors measured simple reaction time (RT) to visual stimuli, presented
      either singly to 1 or the other visual field or in bilaterally presented pairs,
      to 2 women with callosal agenesis. The stimuli were either white against a black
      background or gray against an equiluminant yellow background. RTs to bilateral
      pairs were decreased beyond predictions based on a simple race between
      independent unilateral processes, implying interhemispheric neural summation.
      This effect was enhanced under equiluminance in the participant M.M. whose
      anterior commissure was within normal limits, but not in the participant J.P.
      whose anterior commissure was enlarged. The anterior commissure may act, relative
      to its size, to inhibit cortical activation to bilateral pairs, which then acts
      to decrease subcortical neural summation.

PMID- 12803427
TI  - Bilateral eye movements enhance the retrieval of episodic memories.
AB  - Two experiments examining effects of eye movements on episodic memory retrieval
      are reported. Thirty seconds of horizontal saccadic eye movements (but not smooth
      pursuit or vertical eye movements) preceding testing resulted in selective
      enhancement of episodic memory retrieval for laboratory (Experiment 1) and
      everyday (Experiment 2) events. Eye movements had no effects on implicit memory.
      Eye movements were also associated with more conservative response biases
      relative to a no eye movement condition. Episodic memory improvement induced by
      bilateral eye movements is hypothesized to reflect enhanced interhemispheric
      interaction, which is associated with superior episodic memory (S. D. Christman &
      R. E. Propper, 2001). Implications for neuropsychological mechanisms underlying
      eye movement desensitization and reprocessing (F. Shapiro, 1989, 2001), a
      therapeutic technique for posttraumatic stress disorder, are discussed.

PMID- 12803428
TI  - Working memory in mild Alzheimer's disease and early Parkinson's disease.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) impair working memory (WM).
      It is unclear, however, whether the deficits seen early in the course of these
      diseases are similar. To address this issue, the authors compared the performance
      of 22 patients with mild AD, 20 patients with early PD and without dementia, and
      112 control participants on tests of inhibition, short-term memory, and 2
      commonly administered tests of WM. The results suggest that although mild AD and
      early PD both impair WM, the deficits may be related to the interruption of
      different processes that contribute to WM performance. Early PD disrupted
      inhibitory processes, whereas mild AD did not. The WM deficits seen in patients
      with AD may be secondary to deficits in other cognitive capacities, including
      semantic memory.

PMID- 12803429
TI  - Sexual-orientation-related differences in verbal fluency.
AB  - This study examined the performance of 60 heterosexual men, 60 gay men, 60
      heterosexual women, and 60 lesbians on 3 tests of verbal fluency known to show
      gender differences: letter, category, and synonym fluency. Gay men and lesbians
      showed opposite-sex shifts in their profile of scores. For letter fluency, gay
      men outperformed all other groups; lesbians showed the lowest scores. For
      category fluency, gay men and heterosexual women jointly outperformed lesbians
      and heterosexual men. Finally, gay men outperformed all other groups on synonym
      fluency, whereas lesbians and heterosexual men performed similarly. A difference
      between heterosexual men and women was demonstrated on category and synonym
      fluency only. The findings implicate within-sex differences in the functioning of
      the prefrontal and temporal cortices.

PMID- 12803430
TI  - Executive function, memory, and learning in Tourette's syndrome.
AB  - Young people with Tourette's syndrome (TS) alone, TS plus attention
      deficit/hyperactivity disorder (+ADHD), or TS plus obsessive-compulsive disorder
      (+OCD) were compared with a healthy control group on a set of measures of
      executive functioning, memory, and learning. The TS-alone group was impaired on
      one executive measure involving inhibition and strategy generation but did not
      differ significantly from the healthy control group on other measures. The
      TS+ADHD group showed impairment on several executive measures. There was no
      evidence of impairment in implicit aspects of memory and learning for any of the
      TS groups. The findings are discussed in terms of the frontostriatal hypothesis
      of TS and the contribution of comorbid symptomatology.

PMID- 12803431
TI  - A meta-analytic review of the sensitivity of the Wisconsin Card Sorting Test to
      frontal and lateralized frontal brain damage.
AB  - The author conducted 2 meta-analyses on the Wisconsin Card Sorting Test (WCST).
      The 1st compared participants with frontal lobe damage to those with posterior
      brain damage, whereas the 2nd compared participants with left and right frontal
      damage. Effect sizes based on the difference between groups were calculated for
      WCST variables and a composite measure. Effect sizes for these variables, except
      nonperseverative errors, indicated significantly poorer performance for
      participants with frontal damage. There were no significant differences for the
      left versus right comparisons. Moderator analyses using the composite measure for
      the frontal versus nonfrontal analyses indicated that the largest effect size was
      for dorsolateral damage. Though this study indicates that the WCST is sensitive
      to frontal lobe damage, caveats are discussed.

PMID- 12803432
TI  - Imitative response tendencies in patients with frontal brain lesions.
AB  - It is widely accepted that patients with frontal lesions have problems inhibiting
      automatic response tendencies. Whereas inhibition deficits of overlearned
      responses have been extensively investigated using interference tasks like the
      Stroop task (J. R. Stroop, 1935), it is controversial whether patients with
      frontal brain lesions also have problems inhibiting imitative responses. Using an
      interference paradigm, the present study investigated imitative response
      tendencies in patients with frontal lesions. In addition, it tested whether
      patients deficient in the inhibition of imitative responses correspondingly have
      problems inhibiting overlearned responses. It was found that the group with
      frontal lesions displayed significantly stronger imitative response tendencies
      than the group with nonfrontal lesions. Furthermore, it was shown that the
      inhibition of imitative responses is functionally unrelated to Stroop
      interference.

PMID- 12803433
TI  - Inhibition of ongoing responses following frontal, nonfrontal, and basal ganglia
      lesions.
AB  - The authors investigated the role of the frontal lobes and the basal ganglia in
      the inhibition of ongoing responses. Seventeen patients with frontal lesions
      (FG), 20 patients with lesions outside the frontal cortex (NFG), 8 patients with
      lesions to the basal ganglia (BG), and 20 orthopedic controls (OG) performed the
      stop-signal task that allows the estimation of the time it takes to inhibit an
      ongoing reaction (stop signal reaction time [SSRT]). The FG and the BG showed
      significantly longer SSRTs than the OG. Within the FG, patients with right and
      bilateral lesions showed significantly longer SSRTs than patients with left
      lesions. Results provide evidence for a role of the frontal lobes and the basal
      ganglia in the inhibition of ongoing responses.

PMID- 12803435
TI  - On the use of scaling and clustering in the study of semantic deficits.
AB  - In the past decade, several studies have used scaling and clustering techniques
      to document semantic storage deficits in patients with Alzheimer's disease and in
      schizophrenia. In this article the authors argued that many of the conclusions
      drawn from these studies are unjustified by the data. They reviewed the
      methodology used in these studies and presented data from simulation studies to
      further investigate the validity of their conclusions. The authors elaborate on
      the criteria needed to exclude alternative accounts of the data and present
      empirical data from patients with Alzheimer's disease and normal control
      participants to demonstrate that analyses of the patients' proximity data do not
      provide unambiguous evidence for a generalized semantic storage deficit.

PMID- 12803434
TI  - Delayed nonmatch-to-sample performance in HIV-seropositive and HIV-seronegative
      polydrug abusers.
AB  - Working memory (WM) deficits are common in HIV-seropositive (HIV+) individuals
      and can be amplified by manipulating a variety of task parameters, such as
      increasing memory load or information complexity. The authors investigated the
      role of timing in HIV-associated WM defects by varying the amount of time
      required to maintain information online while holding memory load and information
      complexity constant. The authors studied 50 HIV+ and 35 HIV-seronegative (HIV-)
      polydrug abusers abstinent at testing and well-matched on demographic variables.
      The HIV- group outperformed the HIV+ group across all stimulus-response time
      delays. HIV-associated WM defects are not critically dependent on the amount of
      time stimulus representations must be maintained and might be attributed to
      impaired encoding or retrieval of stimulus representations.

PMID- 12803436
TI  - Things aren't as bad as they seem: a comment on Storms et al. (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003)
      criticized the use of scaling techniques, in proposing "semantic storage
      deficits" in Alzheimer's disease and schizophrenic patients in some studies,
      arguing that most reported multidimensionalscaling (MDS) models for patients were
      not adequately fit and did not differ from models generated by random data. The
      studies cited by G. Storms et al. were reexamined and all available data relevant
      to their claim were compared. A more complete review revealed somewhat different
      conclusions; it showed that many of the MDS models seem to meet the criteria of
      adequate fit, and it does not seem to support the notion that patients'
      performance is close to random. Suggestions are made to improve the validity of
      scaling analysis in neuropsychological studies.

PMID- 12803438
TI  - What are the causes of reduced fit in scaling and clustering studies of semantic
      proximity data, and how else to measure them: a comment on Storms et al. (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) noted
      that the goodness-of-fit indices for scaling and clustering solutions of
      proximity data from populations with hypothesized semantic deficits tend to be
      reduced in comparison with control participants, and that this precludes an
      unambiguous interpretation of such data. However, this effect is not necessarily
      as inconsistent with the proposal of semantic degradation in these groups, or as
      consistent with explanations in terms of access or attentional problems, as is
      suggested by G. Storms et al. Also, although performance on word fluency tasks is
      certainly constrained by the ability to access stored information, there are ways
      in which this confounding influence may be controlled for in the study of
      semantic deficits.

PMID- 12803437
TI  - Structure versus processing deficits in Alzheimer's disease, a matter of degree:
      a comment on Storms et al. (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) argued
      that multidimensional scaling studies are ill-suited for investigating semantic
      deficits in individuals diagnosed with dementia of the Alzheimer type (DAT)
      because such individuals show great inter- and intraindividual variability in
      their proximity judgments. Discussed in this commentary are (a) the possible role
      of attentional set in producing inconsistent performance across trials, (b) the
      implications of attentional factors on the structure versus process debate, and
      (c) the inevitable semantic degradation following severe progression of the
      disease. A framework is presented for considering nonlinear performance
      differences as a function of attentional demands of the task, vulnerability of
      the semantic representation, and progression of the disease.

PMID- 12803439
TI  - Taking the thumbs off the multidimensional scales in the debate on semantic
      memory and Alzheimer's disease: a comment on Storms et al. (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) bring
      into focus at least 3 important issues. First, the performance of even simple
      tasks may be affected by several basic cognitive processes. Second, the
      statistical variance that these processes contribute to task performance may be
      different for a group of participants with neuropsychological deficits than for
      normal control particpants. Third, claims regarding the nature of semantic memory
      in Alzheimer's disease (AD) reflect indeterminacy about the nature and assessment
      of semantic memory itself. Critically, their analysis suggests that the T.
      Shallice and E. K. Warrington (1979) criteria widely used to operationalize the
      semantic memory deficit in AD be carefully scrutinized and reevaluated.

PMID- 12803440
TI  - New directions in the study of semantic deficits: a comment on Storms et al.
      (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstaeten, and P. P. De Deyn (2003) have
      provided an important critique of the use of multidimensional scaling (MDS) to
      evaluate semantic knowledge in Alzheimer's disease. If MDS is to be used with
      semantic proximity data (in spite of well-documented reasons for not doing so),
      at minimum, the issues raised in G. Storms et al. should be considered. A few
      criticisms of the target article are presented. Then, the manner in which key
      points from the article, along with a consideration of such factors affecting
      proximity elicitation as semantic domains, tasks, and the experimental context,
      could be applied to correct certain shortcomings in the literature are discussed.

PMID- 12803441
TI  - Is there madness in the method? A comment on Storms et al. (2003).
AB  - G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. De Deyn (2003) offer a
      critique of multidimensional scaling studies purporting to reveal systematic
      semantic deficits in Alzheimer's disease and other syndromes which, in contrast
      to prior claims, demonstrates that patient performance is indiscriminable from
      random data. The argument is an indictment against the conclusions drawn by
      previous researchers; but a consideration of the materials used in these studies
      suggests that the problem may not lie in the method per se, but in poor stimulus
      design. In all of the similarity judgment tasks reviewed, stimulus items were
      differentiated solely on the basis of subtle conceptual distinctions of the sort
      known to be most vulnerable to semantic impairment. Thus, one would not expect
      systematic responding from semantically impaired patients to begin with. An
      alternative design is suggested.

PMID- 12803442
TI  - Question hard, answer simply: a comment on Storms et al. (2003).
AB  - It seems clear that, for whatever reasons, the dementia of the Alzheimer type
      patient group (as well as other patient groups) exhibits behavior that is
      different from the normal control group. G. Storms, T. Dirikx, J. Saerens, S.
      Verstraeten, and P. P. De Deyn (2003) rightfully argue that the observed behavior
      (similarity judgments) does not tell us the source (cause) of the differences
      between the 2 groups. Rather, the focus of the study should be placed more on
      finding the ways the 2 groups are different. They also point out various
      methodological problems in some of the previous attempts to characterize the
      nature of the differences. Further methodological issues in G. Storms et al.'s
      study are examined.

PMID- 12803443
TI  - Clarifying today's coding and compliance issues. Treatment delivery
      clarification.

PMID- 12803445
TI  - Strategic planning: the first step in the planning process.
AB  - Strategic planning is a systematic process through which an organization builds
      commitment among key stakeholders to goals and priorities which are essential to
      its mission and vision, and responsive to the operating environment. Strategic
      planning is the first step in a comprehensive planning process that also includes
      business planning and implementation planning. If all three steps are carried out
      in sequence, strategic planning can be a very effective means of educating the
      stakeholders about where the cancer program is and where it is going, gaining
      support and commitment for the direction that the cancer program will take, and
      assuring that everyone's expectations can be managed effectively. Unfortunately,
      some organizations and cancer program leaders misunderstand the process. Too
      often, strategic planning is used as a stand-alone activity. This article will
      describe what strategic planning is, how it should smoothly lead into business
      planning and implementation planning, and how to avoid the pitfalls that
      sometimes arise during the strategic planning effort.

PMID- 12803444
TI  - Report from the American College of Oncology Administrators' (ACOA) liaison to
      the American College of Surgeons Commission on Cancer (ACoS-CoC). New cancer
      program standards highlighted.

PMID- 12803446
TI  - Empowering the staff to assist in planning and developing a freestanding
      radiation oncology cancer center.

PMID- 12803447
TI  - Planning for patient privacy and hospitability: a must do in oncology care.
AB  - The number one design challenge in the healthcare environment is the patient
      room. This space is one of the primary functional areas impacting hospital design
      and, quite often, the place of greatest controversy. This controversy is due to
      the length of time the patient spends in the room (compared to other areas), the
      amount of overall space required and the time dedicated to patient room
      utilization, maintenance, general arrangement and overall efficiency. In
      addition, there is a growing list of room types to be considered, many are of the
      ambulatory care, short stay and observation category. Other room types beyond the
      routine medical/surgical room include Intensive Care, Coronary Care, Surgical
      Intensive Care, Skilled Nursing, Rehabilitation and Oncology Care as well as more
      intensive Bone Marrow Transplantation, for example. Major features of the
      traditional acute care patient room require the space to be flexible,
      convertible, expandable and, most importantly, hospitable. For many, many years
      the patient room was considered a shared space with multiple beds and multiple
      users. The term semi-private has been used to describe the traditional two-bed
      and, sometimes 4-bed patient room. This article will address the programmatic
      elements of an inpatient area, the room and its functional components along with
      some examples for comparative purposes. For the oncology patient, the development
      of a family-focused, private room is mandatory. The private room is more
      flexible, less expensive to operate, safer and environmentally more appealing for
      the patient, family and staff.

PMID- 12803448
TI  - Meeting the challanges in today's outpatient oncology setting: a case study.
AB  - Physicians and staff in outpatient oncology settings are feeling besieged as
      healthcare trends accelerate. One of these is to provide a greater number and
      variety of treatments on an outpatient basis. The second is the shift from
      indemnity insurance to a managed care environment to help control the costs. The
      challenge at the Center for Cancer Care at OSF Saint Anthony Medical Center in
      Rockford, Illinois, was to create processes that increased efficiency, dealt with
      expanded patient caseloads, improved the level of care provided and took into
      account the shortage of oncology nurses.

PMID- 12803449
TI  - Midwest takes integration all the way home.

PMID- 12803450
TI  - Risk profiles of adolescent girls who were victims of dating violence.
AB  - The prevalence of dating violence, as well as its relationship to potential risk
      factors, was examined among a nationally representative sample of 9th-through
      12th-grade U.S. females (N = 7,824) who completed the 1999 Youth Risk Behavior
      Survey. The dependent variable was physical dating violence; the independent
      variables were violence, suicide, substance use, and sexual risk behavior.
      Unadjusted odds ratios (OR) and 95% confidence intervals were examined, and
      multivariate logistic regression analysis was conducted to identify the most
      significant risk factors. It was found that nearly one in ten of the adolescent
      girls reported dating violence. Twelfth-grade girls had the highest prevalence of
      dating violence. Girls who were victims of dating violence were more likely to be
      involved in other violent behaviors, to report extreme sadness and suicidal
      actions, to use illicit substances, and to engage in risky sexual behavior.
      Multivariate analysis revealed that dating violence was associated with
      sad/hopeless feelings (OR = 2.13), binge drinking (OR = 1.96), cocaine or
      inhalant use (OR = 2.90), multiple sex partners (OR = 2.38), nonuse of condoms
      (OR = 1.53), and ethnicity, specifically being Black (OR = 2.32) or Hispanic (OR
      = 1.82). These findings provide further evidence that there is a clustering of
      risk factors among certain adolescents, specifically girls who experience dating
      violence.

PMID- 12803451
TI  - Effects of parenting, father absence, and affiliation with delinquent peers on
      delinquent behavior among African-American male adolescents.
AB  - This study examined the effects of different aspects of parenting, father
      absence, and affiliation with delinquent peers on delinquent behavior in a cohort
      of African-American male adolescents. One round of survey data was collected from
      the youths' mothers or mother surrogates (N = 175) and two rounds of survey data
      were collected from the adolescents themselves. Analyses revealed that mothers'
      perceived control of sons' behavior was a deterrent of delinquent behavior, while
      other aspects of parenting (e.g., mother-son communication and relations) were
      not. The effect of mothers' perceived control was not mediated by adolescents'
      affiliation with delinquent peers. The effects of mothers' parenting variables
      and peer affiliation did not vary significantly by family structure, but
      socioeconomic disadvantage was more strongly associated with delinquent behavior
      in father-absent families. Though parenting effects were modest, this study
      suggests that African-American male adolescents are less likely to engage in
      delinquent behavior if they are closely monitored and supervised by their
      parents.

PMID- 12803452
TI  - Academic performance, popularity, and depression predict adolescent substance
      use.
AB  - Eighty-nine high school seniors completed a questionnaire on their feelings and
      activities, including their use of drugs. Adolescents with a low grade point
      average, high popularity, and high depression were more likely to smoke
      cigarettes, drink alcohol, and smoke marijuana than were their peers. Cigarette
      and alcohol use predicted marijuana use, which in turn predicted cocaine use.

PMID- 12803453
TI  - The Sexual Communication Scale: a measure of frequency of sexual communication
      between parents and adolescents.
AB  - This study reports on the psychometric properties of a brief instrument that can
      be used in research or practice to measure the frequency of communication about
      sexual matters between parents and adolescents: The Sexual Communication Scale
      (SCS). The instrument was designed to assess communication between a
      mother/mother-figure and an adolescent and between a father/father-figure and an
      adolescent. The instrument, which contains 20 items for mothers and the same 20
      for fathers, addresses sexual topics ranging from dating to sexual intercourse to
      homosexuality to HIV/AIDS. The sample used to establish reliability and validity
      of the SCS consisted of 158 males and females, who were primarily Caucasian,
      suburban, low to upper middle socioeconomic status, and in the 9th through 12th
      grades. Factor analyses revealed a strong unidimensional construct. Further,
      internal consistency was found to be very high. In sum, the SCS demonstrated
      adequate psychometric properties.

PMID- 12803454
TI  - The relationship between depression and smoking in adolescents.
AB  - The literature suggests that smokers are more likely to be depressed, while
      people who are depressed are more likely to smoke. The purpose of the present
      study was to determine the strength of the relationship between smoking,
      depression, intention to smoke, and several psychosocial and environmental
      factors. The participants (98 high school and college students aged 16 to 19
      years) completed a paper-and-pencil questionnaire consisting of the Multiscore
      Depression Inventory (MDI) and items regarding smoking behavior as well as
      psychosocial and environmental factors. Correlation, stepwise regression, and
      discriminant analyses were then conducted. It was found that participants were
      more likely to smoke if their parents smoked, if their scores on the MDI
      indicated instrumental helplessness and social isolation/withdrawal, or if they
      were older. Participants were more likely to state intention to smoke in the
      future if they had MDI scores indicating instrumental helplessness, if they were
      older, if their parents smoked, if their MDI scores indicated social intro
      version, or if they resided with a guardian. Participants were also more likely
      to have smoked for more years if their parents smoked or if their scores on the
      MDI indicated instrumental helplessness. Further, participants were more likely
      to have scores on the MDI indicative of higher depression levels if they had low
      grades or if their parents smoked.

PMID- 12803455
TI  - Self-reported delinquency among Alberta's youth: findings from a survey of 2,001
      junior and senior high school students.
AB  - This article draws on data from a 1999 survey on youth victimization, crime and
      delinquency in Alberta conducted by the Canadian Research Institute for Law and
      the Family in collaboration with researchers from the University of Alberta. The
      survey included 2,001 youth attending Grades 7 to 12 in public and Catholic
      schools in selected urban and rural areas in the province. Analyses focus on self
      reported past-year delinquency. Statistically significant results were found for
      relationships between extent of delinquency and gender, grade level, psychosocial
      problems (as measured by conduct, hyperactivity, and emotional problems), and
      extent of past-year victimization. For low/moderate delinquency, females were
      comparable to males, and even reported slightly higher rates for low/moderate
      violence-related delinquency. Younger students were more likely to indicate
      engaging in violence-related delinquency, while older students were more likely
      to report property-related delinquent acts. Overall, Grade 9 students had the
      highest rates of delinquency. For personal characteristics, a high score on
      conduct problems was most strongly correlated with moderate/high delinquency. The
      relationship between high levels of delinquency and victimization was stronger
      for violence-related delinquency than for property-related delinquency.

PMID- 12803456
TI  - Understanding depressed mood in the context of a family-oriented culture.
AB  - This study examined the contribution of individual and family variables to
      depressive symptoms among youths in a family-centered culture. Participants were
      262 Mexican adolescents (mean age = 15.9 years). At the individual level, gender
      (being female) and higher levels of perceived stressfulness of life events and
      ruminative coping style were correlated with higher frequency of depressive
      symptoms. At the family level, higher levels of perceived parental warmth and
      acceptance and parental monitoring were correlated with lower levels of depressed
      mood, whereas higher levels of parent-adolescent conflict were associated with
      greater frequency of depressive symptoms. Regression analyses confirmed our
      prediction that both individual factors (gender, ruminative coping) and family
      factors (parental warmth and parental monitoring) would make unique contributions
      to depressive symptoms. The model comprised of individual and family variables
      accounted for 50% of the variance in depressed mood. Moreover, parental warmth
      and acceptance attenuated the impact of ruminative coping style on adolescents'
      depressive symptomatology. Findings are discussed in relation to previous
      research on adolescents in another family-centered culture (China), and
      directions for future research are proposed.

PMID- 12803457
TI  - Adolescent coping in different Chinese family environments.
AB  - This study explored the relationship between family environment and adolescent
      coping in a Chinese sample. Four family types were identified with cluster
      analysis: (a) conflict-control, (b) structured, cohesive, expressive, and
      recreation-oriented, (c) structured, cohesive, and low conflict, and (d)
      unstructured and low control. Families with high cohesion, expressiveness,
      organization, low conflict, and low to medium level of control were associated
      with a more constructive coping style. Chinese adolescents tended to (a) mobilize
      personal resources, (b) seek help from social resources, and (c) adopt a
      philosophy of doing nothing as their major coping style when they had a positive
      perception of their family environment. This coping style was termed "fatalistic
      voluntarism." Finally, boys' coping behaviors were somewhat different from
      girls'. Girls tended to rely more on social support, whereas boys tended to avoid
      the problem or engage in blaming.

PMID- 12803458
TI  - School vandalism: individual and social context.
AB  - Six hundred Israeli students responded to a questionnaire dealing with five
      motives for participating in vandalism: anger/frustration, boredom, erosion,
      aesthetics, and catharsis (Cohen, 1984). As we did not find a coherent pattern,
      we created a variable comprising all five motives: general motivation. Four
      factors accounted for motivation to participate in destructive behavior:
      perceived level of vandalism at school, attitude toward school, attitude toward
      teacher, and school anxiety. Punishment, father's level of education, sense of
      hope, and class level did not have an effect on motivation to participate in
      vandalism. It was concluded that the social context is a crucial element in
      school vandalism.

PMID- 12803459
TI  - "I want to read stuff on boys": white, Latina, and black girls reading seventeen
      magazine and encountering adolescence.
AB  - This study is based on interviews with four focus groups consisting of fourteen
      white, Latina, and black girls, ages 13 to 16 years, from diverse backgrounds.
      The objectives of the study are to gain insight into what forum girls use to
      learn about the adolescent experience and to examine teenage girls' views of
      their sexuality and femininity. The girls' discussion of their lives and
      perceptions of the teen magazine Seventeen reveal a displacement of female
      sexuality. The magazine's message to teenage girls of gaining self-worth through
      emphasized femininity seems to resonate with these girls regardless of class and
      race. We conclude that responsible adults need to challenge the distorted media
      images of adolescent development and teenage girls' sexuality.

PMID- 12803460
TI  - Motivations and attitudes affecting high school students' choice of foreign
      language.
AB  - There are some foreign languages that enjoy great status in the United States,
      while other foreign languages are rarely represented at the high school level.
      The present study explored the following questions: Why do students choose to
      take a particular foreign language? Do students gravitate toward it because it is
      widely thought to be the easiest language to learn or because they perceive
      greater career opportunities with proficiency in this particular language, or is
      it simply because there are more classes offered? As long as foreign language
      study is elective in high schools and as long as a variety of languages are
      offered, the answers to these questions will remain important for foreign
      language educators, especially in schools where the various language programs
      compete with one another for student enrollments and the programs' ultimate
      survival.

PMID- 12803461
TI  - Labeling and delinquency.
AB  - The present study examined a procedure for measuring perceived labeling. An index
      comprised of six contrasting descriptive adjectives was used to measure
      incarcerated youths' perceived negative labeling from the perspective of parents,
      teachers, and peers. The results provided partial support for the hypothesis that
      juveniles who choose a greater number of negative labels for their self-concepts
      will report more frequent delinquent involvement. Labeling variables were
      significant predictors of general and serious delinquency but did not predict
      drug-related offenses.

PMID- 12803462
TI  - Isolation of the enhanced neurovirulent HSV-1 strains from Korean patients.
AB  - Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus which has latency
      in human. In this study, we isolated various HSV-1 strains, named KHS, from the
      skin lesions of Korean patients and characterized the specific features of each
      strain. We found that KHS strains produced small, cell associated and
      nonsyncycial plaques in Vero cells. We classified KHS strains into two
      substrains, KHS 1 which had highly condensed plaques and KHS 2 which had less
      condensed plaques. Since gD protein of HSV-1 plays important roles in viral
      plaque formation, we determined the nucleotide sequences of gD genes of KHS
      strains. According to deduced amino acid sequences of gD protein in KHS strains
      compared with prototype strains KOS and F, we found that gD of KHS strains have
      more putative O-glycosidic sites, serine in KHS 1 and threonine in KHS 2,
      respectively. To find out the establishment of viral latency, we infected each
      virus strain into eyes of mice and carried out trigerminal ganglia explanting
      experiment. We found that both KHS strains established latent infections stably
      just as did the prototype KOS and F strains. The eye swab experiments were
      carried out to check the viral replication in vivo. KHS 1 exhibited a longer
      shedding time in eyes of mice. We also found that KHS 1 has a higher neurotropic
      affinity by determining the time it took for the virus to reach the trigerminal
      ganglia from the eyes. Currently, we are studying the possible mechanism of high
      neuroinvasiveness of KHS 1 strain.

PMID- 12803463
TI  - Immunological and regulatory functions of uninfected and virus infected immature
      and mature subtypes of dendritic cells--a review.
AB  - In 1868, dendritic cells (DCs) were discovered in human skin by Paul Langerhans
      using gold staining. These cells were named Langerhans cells (LCs) after their
      discoverer who, due to their dendrites, regarded them as neurons. One hundred and
      eleven years were to pass until it was discovered that in vertebrates these cells
      originate in the bone marrow as monocytes. In the 1980s, DC research was mostly
      carried out on DCs that are present in different tissues of mice and humans.
      These studies revealed that after interaction with foreign antigens, skin LCs/DCs
      migrate through the lymph vessels to the draining lymph nodes and induce the two
      arms of the immune response. The isolation of DCs from tissue cell suspensions
      opened the way to studies on the cells' surface proteins and their ability to
      stimulate immune responses. During the 1990s, studies revealed the role of DCs in
      the activation of naive T cells in the lymph nodes and the regulatory properties
      of DCs in lymph nodes, thymus, gut, and spleen. Part A of the review deals with
      the DC system of human and mice and immunological and regulatory functions of
      subsets of DCs in the skin with reference to migrating and stationary DCs, as
      well as the connection between DCs and the nervous system. Furthermore, the
      origin of both follicular DCs that are present in lymphoid tissues and thymic DCs
      are discussed. Part B is devoted to virus infections of DCs with an emphasis on
      infections caused by human herpes viruses. Part C presents the modulation of DC
      gene expression in response to the influenza virus. Contemporary research focuses
      on the role of DCs in the immune systems of vertebrates. Moreover, studies are
      being conducted on the regulatory functions of DCs by tissue cells in different
      organs of vertebrates.

PMID- 12803464
TI  - Milestones in the research on skin epidermal Langerhans/dendritic cells (LCs/DCs)
      from the discovery of Paul Langerhans 1868-1989.
AB  - Almost 100 years elapsed after the discovery of dendritic cells in the human skin
      epithelium by Paul Langerhans in 1868 until the initiation of research on those
      cells was reinitiated. The present paper provides the milestones in the research
      on Langerhans/dendritic cells (LCs/DCs) between 1960 and 1989. This historical
      review will explain how researchers gradually discovered the role of the bone
      marrow-derived dendritic cells in the immune response. The paper is an appendix
      to the manuscript entitled: "Immunological and regulatory functions of uninfected
      and infected immature and mature subtypes of dendritic cells" (Virus Genes 26:
      119-130, 2003).

PMID- 12803465
TI  - Phylogenetic relationships of West Nile viruses isolated from birds and horses in
      Israel from 1997 to 2001.
AB  - In November 1997, an outbreak of a neuroparalytic disease caused by West Nile
      (WN) virus was diagnosed in young goose flocks. Domestic geese were similarly
      affected in the late summer and fall of 1998, 1999, 2000 and 2001. WN viruses
      were also isolated from migratory and wild birds and horses in 1998-2001. A 1278
      bp sequence of the envelope gene of 24 Israeli WN virus isolates was compared
      with those of seven isolates from Africa, Europe and New York. As a result, the
      Israeli isolates could then be grouped into two clusters. The 15 avian and three
      equine from 1997-2001 in the first cluster of viruses were shown to be identical
      to WN-NY99, while the second cluster comprised one goose isolate from 1998 and
      two goose and two pigeon isolates from 2000. These closely resembled the most
      recent Old World isolates, and indicate that at least two WN genotypes were co
      circulating in the region during this time.

PMID- 12803466
TI  - Identification and classification of the Spodoptera littoralis
      nucleopolyhedrovirus inhibitor of apoptosis gene.
AB  - Baculoviruses possess two types of genes that suppressed apoptosis, p35 and
      inhibitor of apoptosis (iap). In this study we report the isolation and
      identification of an inhibitor of apoptosis gene Sliap in the genome of the
      Spodoptera littoralis nucleopolyhedrovirus (SINPV). The Sliap sequence predicted
      a 15 kDa polypeptide with only one BIR domain and a RING finger, both motifs
      characteristic of the IAP family of proteins, and a third specific acidic-rich
      motif. These characteristics, shared with the Spodoptera littura NPV IAP2/3,
      Epiphyas postvittana NPV IAP4, Lymantria dispar NPV IAP and Orgyia pseudotsugata
      NPV IAP4 (Orf 107) allowed us to classify them in a new homology group (IAP-4).
      Sliap was able to delay, but not to suppress, apoptosis induced by replication of
      a recombinant AcMNPV deficient in p35. In SINPV infected-SF9 cells Sliap was
      expressed earlier than sl-p49 suggesting that its role at the initiation of
      infection was to delay the apoptotic response of the host.

PMID- 12803468
TI  - Epstein-Barr virus DNA is detected in peripheral blood mononuclear cells of EBV
      seronegative infants with infectious mononucleosis-like symptoms.
AB  - We demonstrated Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear
      cells (PBMCs) from infants with infectious mononucleosis- (IM) like symptoms.
      Thirteen of the 17 patients did not have EBV antibodies; however, EBV DNA was
      detected in 8 PBMC from the 13 seronegative patients by PCR. The 4 patients were
      retested in 6-12 months later. Three patients were still seronegative; however
      EBV DNA wasnot detected. One patient seroconverted and EBV DNA could still be
      detected. The transcript of EBNA1 was detected in one patient, but neither EBNA2
      nor LMP2A were detected in all PBMC from the 4 tested patients. Type 1 EBV DNA
      was detected in 5 PBMC of 7 tested patients, and type 2 EBV DNA was detected in
      type 1 positive PBMC of one patient as well. The IL-1 beta polymorphism that is
      reported to be one of the immunological factors of EBV seronegativity revealed no
      difference in IM-like patients. These results indicated that EBV infection occurs
      in EBV-seronegative IM-like infants; however, the modes of infection are clearly
      different from IM.

PMID- 12803469
TI  - Molecular characterisation of three avian paramyxovirus type 1 isolated from
      pigeons in France.
AB  - Three avian Paramyxovirus type 1 (aPMV-1) isolated from pigeons duringpigeon
      paramyxovirosis outbreaks were molecularly characterised by sequencing parts of
      the six genes (NP, P, M, F, HN and L) of each strain. Virulent 99143 isolate was
      found to be very closely related to non-pathogenic vaccine strains of aPMV-1,
      even for its F protein cleavage site motif. Strains 99299 and 99106, typical
      pigeon paramyxovirus type 1 (pPMV-1) variants, exhibited between 10% and 20%
      difference with aPMV-1 at the nucleotide level. The aPMV-1 specific pattern of
      eight amino acids in the intracellular domain of HN protein was found different
      by one residue for these two isolates, and might represent a specific pattern for
      pPMV-1. The unique sequence of the polycistronic P gene editing site of 99299 and
      99106 was characterised by four instead of three cytosine residues, and might so
      have an influence on the expression level of the three proteins encoded by P.
      This work is also the first to provide molecular data on NP, P and L genes of
      typical pPMV-1.

PMID- 12803470
TI  - A human vaccine strain of lamb rotavirus (Chinese) NSP4 gene: complete nucleotide
      sequence and phylogenetic analyses.
AB  - A lamb strain of rotavirus has recently been licensed for use in China as a live
      vaccine to prevent rotavirus diarrhea in children. As rotavirus NSP4, especially
      the cytotoxic domain alone is considered to be associated with diarrhea, we
      sequenced gene segment 10, which encodes NSP4, of lamb rotavirus. Comparative
      analyses was performed to identify differences from human rotavirus strains, that
      might be associated with attenuation, and to ascertain whether the lamb rotavirus
      gene fits among the NSP4 of other sequenced rotavirus strains. Our comparative
      nucleotide sequence analysis suggests its close identity (91.17% homology) with
      that of group-A equine rotavirus (strain HI23). Multiple alignment of the deduced
      amino acid sequence of lamb NSP4 with that of other group A rotaviruses
      demonstrated homology ranging from 63.42% with that of porcine YM strain to
      93.71% with equine HI23 strain of rotavirus. A group A-specific NSP4 monoclonal
      antibody recognized the glycosylated and unglycosylated forms of the protein from
      virus-infected lysates, suggesting a well-conserved group-specificity of the lamb
      NSP4. Phylogenetic analysis of the lamb rotavirus gene, with 60 other NSP4 gene
      sequences of human and animal rotavirus strains, demonstrated that the lamb
      rotavirus strain belongs to genotype A. Comparative analysis also revealed that
      although it is a vaccine strain, the NSP4 cytotoxic domain of lamb strain
      demonstrated an overall amino acid conservation similar to that of other strains,
      whose NSP4 alone causes diarrhea in animal models. These results taken together
      with our previous observations clearly reaffirm the idea that the attenuation
      phenotype of rotaviruses does not involve NSP4 cytotoxic domain, perhaps due to
      the suppression of NSP4 cytotoxic activity by other rotaviral proteins.

PMID- 12803467
TI  - Evolution and diversity of HIV-1 in Africa--a review.
AB  - The HIV/AIDS pandemic represents a major development crisis for the African
      continent, which is the worst affected region in the world. Currently, almost 30
      of the 42 million people infected with HIV worldwide live in Africa. AIDS in
      humans is caused by two lentiviruses, HIV-1 and HIV-2, which entered the human
      population by zoonotic transmissions from at least two different African primate
      species. Extensive phylogenetic analyses of partial and full-length genome
      sequences have helped to gain insights into the evolutionary biology and
      population dynamics of HIV. One of the major characteristics of HIV is its rapid
      evolution, which has resulted in substantial genetic diversity amongst different
      isolates, the majority of which are represented in Africa. Genetic variability of
      HIV and any consequent phenotypic variation poses a significant challenge to
      disease control and surveillance in different geographic regions of Africa. This
      review focuses on the origins and evolution of HIV, current classification and
      diversity of HIV isolates in Africa and provides an extensive account of the
      geographic distribution of HIV types, groups, and subtypes in each of the 49
      African countries. Numerous epidemiological studies have provided a picture of
      HIV distribution patterns in most countries in Africa, and these show increasing
      evidence of the importance of HIV-1 recombinants. In particular, this review
      highlights that our current understanding of HIV distribution in Africa is
      incomplete and inadequately represents the diversity of the virus, and
      underscores the need for ongoing surveillance.

PMID- 12803471
TI  - Cloning and sequencing of complete cDNA of Japanese encephalitis virus YL strain
      in Taiwan.
AB  - We determined the complete nucleotide sequence of the YL strain of Japanese
      encephalitis virus and its amino acid sequence was deduced. Our results displayed
      that the genome of YL strain contained a single open reading frame of 10,296
      nucleotides (nts) which was flanked by untranslated region (UTR) containing 95
      bases at the 5'-end and 586 bases at the 3'-end, respectively. Comparison of
      sequences showed that the overall amino acid sequence and 3' UTR of YL were
      similar to those of the virulent strain JaGAr0l. However, some significant amino
      acid differences of viral envelope (E) protein were observed between YL and
      JaGAr01; the amino acid sequence of E protein in YL strain possessed RGG(387-389)
      tripeptide instead of RGD(387-389) in JaGAr01 and in other strains; and another
      amino acid is K(138) in YL, not E(138) found in others. These differences
      suggested that the YL strain impairs in viral attachment to the cell surface and
      loses neuroinvasiveness, and therefore this strain was used as a live attenuated
      vaccine.

PMID- 12803473
TI  - Cloning and sequence analysis of the nucleocapsid gene of porcine epidemic
      diarrhea virus Chinju99.
AB  - The nucleocapsid (N) gene of the porcine epidemic diarrhea virus (PEDV) Chinju99
      which was previously isolated in Chinju, Korea was cloned and sequenced to
      establish the information for the development of genetically engineered
      diagnostic reagents. Also, sequences of the nucleotides and deduced amino acids
      of the Chinju99 N gene were analyzed by alignment with those of CV777 and Brl/87.
      The nucleotide sequence encoding the entire N gene open reading frame (ORF) of
      Chinju99 was 1326 bases long and encoded a protein of 441 amino acids with
      predicted M(r) of 49 kDa. It consisted of 405 adenine (30.5%), 293 cytosine
      (22.1%), 334 guanines (25.2%) and 294 thymines (22.2%) residues. The Chinju99 N
      ORF nucleotide sequence was 96.5% and 96.4% homologous with that of the CV777 and
      Brl/87, respectively. The Chinju99 N protein revealed 96.8% amino acid identity
      with that of Brl/87 and CV777, respectively. The amino acid sequence contained
      seven potential sites for threonine (T)- or serine (S)-linked phosphorylation by
      each protein kinase C and casein kinase II.

PMID- 12803474
TI  - Anopheles gambiae genome: perspectives for malaria control.
AB  - Malaria, a disease that infects 300 million people throughout the world and kills
      more than a million people, mostly children in sub-Saharan Africa, involves three
      organisms. The human host where the disease is seen, the protozoan Plasmodium
      parasite and the mosquito. The parasite is transmitted to humans only by the
      mosquito vector, which in sub-Saharan regions is generally Anopheles gambiae.
      Malaria along with AIDS and tuberculosis are killing large numbers of people and
      crippling the economies of the affected African countries. Though an enormous
      effort has been made during the past twenty years to develop vaccines to block
      malaria in humans, the incidence of the disease is increasing in Africa. The
      reasons for this development include a breakdown in mosquito control related to
      increased insecticide resistance, as well as increased parasite resistance to
      antimalarial drugs. It is clear that new methods of Anopheles mosquito control
      are needed to ameliorate the medical and economic situation in sub-Saharan
      Africa. As a step toward new malaria control methods, the international
      Plasmodium falciparum and Anopheles gambiae consortia have carried out the full
      genome sequencing of the most deadly malaria parasite and the most efficient
      vector. These, combined with the human genome sequence, provide the genomic
      infrastructure for a better understanding of the complex interactions within the
      malaria triad. This essay discusses possible strategies as to how the Anopheles
      genome can contribute to malaria control.

PMID- 12803472
TI  - Matrix protein gene sequence analysis of avian paramyxovirus 1 isolates obtained
      from pigeons.
AB  - The matrix protein gene was cloned and sequenced for several recent isolates of
      avian paramyxovirus type 1 (APMV-1). Specifically, isolates from pigeons and
      doves, members of the Columbidae family were examined. APMV-1 is the causative
      agent of Newcastle disease and the virus is associated with disease among a
      diverse number of avian species. Newcastle disease virus (NDV) isolates from
      pigeons have also been classified as pigeon paramyxovirus type 1 (PPMV-1). Matrix
      protein gene sequences for PPMV-1 isolates clustered together as a group relative
      to isolates from other species phylogenetically. However, there were also
      isolates from pigeons or doves that grouped with APMV-1 isolates from other
      species. This indicates that PPMV-1 may be circulating among Columbidae members
      as a distinct lineage, but that these avian species may also harbor other NDV
      strains as well. Of particular interest was a dove isolate from Europe that had
      an aberrant fusion protein cleavage site and was an outlying member
      phylogenetically between the two major groups of APMV-1 isolates.

PMID- 12803475
TI  - Malaria parasites and red blood cells: from anaemia to transmission.
AB  - Malaria parasites, Plasmodium spp., invade and exploit red blood cells during
      their asexual expansion within the vertebrate host. The parasite has evolved a
      suite of adaptive mechanisms enabling optimal exploitation of the host blood cell
      environment, avoiding host destruction, maintaining a parasite reservoir of
      infection and producing sexual transmission stages to infect mosquitoes. The
      highly variable nature of the host blood environment, both over the course of an
      infection and as a result of other parasitic infections, has selected for the
      evolution of considerable phenotypic plasticity in the parasite's response to its
      environment, particularly those phenotypes concerning transmission of the
      parasite to mosquitoes. With the evolution of human society, human malaria
      disease is becoming an increasingly urban problem. This imposes different
      selection pressures on the parasite. The extent to which the parasite is truly
      plastic over the short term rather than adaptive over the long term will
      determine the urban epidemiology of malaria and is essential for developing
      appropriate control methods. Understanding the adaptive nature of malaria
      parasites is thus vital for anticipating the future visage of urban human
      malaria.

PMID- 12803476
TI  - Identification of the Anopheles gambiae ATP-binding cassette transporter
      superfamily genes.
AB  - The Anopheles gambiae genome sequence has been analyzed to find ATP-binding
      cassette protein genes based on deduced protein similarity to known family
      members. A nonredundant collection of 44 putative genes was identified including
      five genes not detected by the original Anopheles genome project machine
      annotation. These genes encode at least one member of all the human and
      Drosophila melanogaster ATP-binding protein subgroups. Like D. melanogaster, A.
      gambiae has subgroup ABCH genes encoding proteins different from the ABC proteins
      found in other complex organisms. The largest Anopheles subgroup is the ABCC
      genes which includes one member that can potentially encode ten different
      isoforms of the protein by differential splicing. As with Drosophila, the second
      largest Anopheles group is the ABCG subgroup with 12 genes compared to 15 genes
      in D. melanogaster, but only 5 genes in the human genome. In contrast, fewer ABCA
      and ABCB genes were identified in the mosquito genome than in the human or
      Drosophila genomes. Gene duplication is very evident in the Anopheles ABC genes
      with two groups of four genes, one group with three genes and three groups with
      two head to tail duplicated genes. These characteristics argue that the A.
      gambiae is actively using gene duplication as a mechanism to drive genetic
      variation in this important gene group.

PMID- 12803477
TI  - Network approaches to genome annotation and the challenge of Anopheles gambiae.
AB  - The rapid advancement of current sequencing projects has provided significant
      challenges for the swift and accurate processing, integration and analysis of
      biological data. Such challenges will only become greater as a new round of
      organisms, both well known and obscure, await sequencing and further study. While
      perhaps less well studied at the molecular level than Drosophila melanogaster,
      the recently sequenced mosquito, Anopheles gambiae, provides an example of what
      will be faced by many of these awaiting projects. This review presents a brief
      overview of some of the challenges associated with these future genome projects
      (including Anopheles) as well as a description of recent computational approaches
      that utilize genome context for the prediction of gene and/or protein function.
      Such approaches show promise not only for the study of Anopheles, but also in the
      study of biological processes in general.

PMID- 12803478
TI  - Telomeres and telomerase in aging, regeneration and cancer.
AB  - The finding that telomere shortening limits the replicative lifespan of primary
      human cells has fueled speculations that telomere shortening plays a role during
      aging and regeneration of tissues in vivo. Support for this hypothesis comes from
      studies showing telomere shortening in a variety of human tissues as a
      consequence of aging and chronic disease. Studies in telomerase-deficient mice
      have given first experimental support that telomere shortening limits the
      replicative potential of organs and tissues in vivo and have identified
      telomerase as a promising target to treat regenerative disorders induced by
      telomere shortening. A potential downside of such an approach could be the
      development of malignant tumors, which has been linked to reactivation of
      telomerase in human cancers. In telomerase-deficient mice, telomere shortening
      showed a dual role in tumorigenesis, enhancing the initiation of tumors by
      induction of chromosomal instability but inhibiting tumor progression by
      induction of DNA-damage responses. The success in using telomerase activation for
      the treatment of regenerative disorders could depend on which of the mechanisms
      of telomere shortening is dominantly effecting carcinogenesis.

PMID- 12803479
TI  - Differentiation of CD34+ cells from human cord blood and murine bone marrow is
      suppressed by C6 beta-chemokines.
AB  - Several recently identified chemokines, Lkn-1, CKbeta8-1, MRP-2, and Mu C10 (MRP
      1), are classified as C6 beta-chemokines. All of these chemokines have been found
      to suppress colony formation by bone marrow (BM) myeloid progenitors. Since cord
      blood (CB), like BM, contains CD34-positive cells, we examined the effects of
      these chemokines on CD34+ cells isolated from human CB. Lkn-1 and CKbeta8-1
      suppressed colony formation by multi-potential granulocyte erythroid mega
      karyocyte macrophages (CFU-GEMM), granulocyte-macrophages (CFU-GM), and erythroid
      (BFU-E) cells among the CD34+ cells from CB. CC chemokine receptor 1 (CCR1) that
      is known to be a receptor for Lkn-1 and CKbeta8-1 in neutrophils, monocytes, and
      lymphocytes, was also present on the surface of CD34+ cells from CB. Taken
      together these results suggest that Lkn-1 and CKbeta8-1 are active in inhibiting
      myeloid progenitor cells from both BM and CB. Macrophage inflammatory protein
      related protein-2 (mMRP-2) and Mu C10 (mMRP-1), which are murine C6 beta
      chemokines, also inhibited colony formation by CB CD34+ cells. The inhibitory
      activity of these chemokines suggests that they may protect hematopoietic
      progenitors from the cytotoxic effects of the antiblastic drugs used in cancer
      therapy.

PMID- 12803480
TI  - Expression of the mitochondrial ATPase6 gene and Tfam in Down syndrome.
AB  - We investigated the expression of the mitochondrial ATPase6 gene whose product is
      active in oxidative phosphorylation (OXPHOS), and compared it to the expression
      of Tfam, an important regulator of the transcription and replication of mtDNA.
      Our aim was to examine a possible relation between mitochondrial gene expression
      and Down syndrome. The expression of ATPase6 and Tfam was analyzed by RT-PCR
      amplification of the mRNA in cultured amniocytes from Down syndrome and normal
      fetuses. The band intensities obtained were normalized against those of HPRT. The
      Down syndrome fetuses were found to have lower ATPase6 and Tfam expression than
      the normal fetuses. This finding suggests that mitochondrial dysfunction
      resulting from decreased ATPase6 and Tfam expression during meiotic oocyte
      maturation of oocytes might affect ATP generation and cause the nondisjunctional
      error. Hence this study suggests that mitochondrial dysfunction may be associated
      with the developmental mechanism of Down syndrome.

PMID- 12803481
TI  - The hierarchical relationship among the spitz/Egfr signaling genes in cell fate
      determination in the Drosophila ventral neuroectoderm.
AB  - The spitz class and Egfr signaling (spi/Egfr) genes are required for the proper
      establishment of cell fate in the Drosophila ventral neuroectoderm. We
      investigated the role of the central nervous system (CNS) midline cells, and the
      hierarchical relationship among the spi/Egfr genes, in this process by analyzing
      the spatial and temporal expression of several of the genes in selected spi/Egfr
      mutants. Our analysis showed that expression of all the spi/Egfr genes is
      severely reduced in the single-minded (sim) mutant, and ectopically induced in en
      Gal4/UAS-sim embryos. This result indicates that sim acts upstream of all the
      other spi/Egfr genes. The CNS midline cells regulate rhomboid (rho) expression in
      the ventral neuroectoderm and activate the EGFR signaling pathway. We also found
      that argos (aos) and orthodenticle (otd) act downstream of pointed (pnt), and
      that aos represses expression of otd in the lateral neuroectoderm to establish
      differential cell fates in the ventral neuroectoderm. Our findings suggest the
      following hierarchical relationship among the spi/Egfr genes: [see text].

PMID- 12803482
TI  - Modification and inactivation of human Cu,Zn-superoxide dismutase by
      methylglyoxal.
AB  - Methylglyoxal (MG) has been identified as an intermediate in non-enzymatic
      glycation, and increased levels have been reported in patients with diabetes. In
      this study, the effect of MG on the structure and function of human Cu,Zn
      superoxide dismutase (SOD) was investigated. MG modifies Cu,Zn-SOD, as indicated
      by the formation of fluorescent products. When Cu, Zn-SOD was incubated with MG,
      covalent crosslinking of the protein increased progressively. MG-mediated
      modification of Cu,Zn-SOD led to loss of enzymatic activity and release of copper
      ions from the protein. Radical scavengers inhibited the crosslinking of Cu,Zn
      SOD. When Cu,Zn-SOD that had been exposed to MG was analyzed, glycine, histidine,
      lysine, and valine residues were found to be particularly sensitive. It is
      suggested that oxidative damage to Cu,Zn-SOD by MG may perturb cellular
      antioxidant defense systems and damage cells. This effect may account, in part,
      for organ deterioration in diabetes.

PMID- 12803483
TI  - Accumulation of microtubule-associated proteins in the hippocampal neurons of
      seizure-sensitive gerbils.
AB  - We have carried out a chronological and comparative analysis of microtubule
      associated protein 1A (MAP1A) and microtubule-associated protein 2 (MAP2)
      immunoreactivities in the hippocampi of seizure-resistant (SR) and seizure
      sensitive (SS) gerbils. These animals represent excellent genetic models of
      epilepsy associated with different sequelae of spontaneous seizures. Both MAP1A
      and MAP2 immunoreactivities were detected in the granule cell layer and in the
      hilar neurons of SR gerbils. In contrast with the SR gerbils, some neurons
      containing MAPs immunoreactivities were scattered in the molecular layer of the
      dentate gyrus as well as being concentrated in the hilar neurons in the SS
      gerbils. An increase in MAP1A immunoreactivity was evident in the perikarya of
      the dentate gyrus at 30 min postictal, whereas MAP2 immunoreactivity decreased.
      MAP1A immunoreactivity in the hilar neurons declined significantly by 3 h
      postictal, whereas MAP2 immunoreactivity increased. These results suggest that
      the immunoreactivity of MAPs in the hippocampal complex differs between SR and SS
      gerbils, and that this difference may be the results of seizure activity.

PMID- 12803484
TI  - Cloning, mutagenesis, and expression of the acetylcholinesterase gene from a
      strain of Musca domestica; the change from a drug-resistant to a sensitive
      enzyme.
AB  - Insect acetylcholinesterase (AChE) is known to be a primary target of
      organophosphorus and carbamate insecticides. However chronic exposure to these
      chemicals has led to resistance to applied insecticides, due usually to mutation
      of the AChE gene. Analysis of the AChE gene (hm) of Musca domestica (the
      housefly), which is cloned in this report, reveals the relationship between
      mutation and insecticide resistance. The 2,076 bp hm encodes a mature protein of
      612 amino acids (67 kDa), and an 80 residue signal peptide. Unlike the enzyme of
      'sensitive' strains, the AChE used in this study was resistant to the
      organophosphorus insecticide, trichlorphon. DNA sequencing showed that this AChE
      is identical to that of the sensitive strains with the exception of three amino
      acids Met-82, Ala-262, and Tyr-327. Site-directed mutagenesis of the Ala-262 and
      Tyr-327 residues largely restored sensitivity to the insecticide, suggesting that
      these two residues are the key structural elements controlling sensitivity. In
      addition to these residues, Glu-234 and Ala-236 in the conserved sequence FGESAG
      are thought to play a role in modulating sensitivity to organophosphorus
      insecticides.

PMID- 12803485
TI  - The structure of the rat ameloblastin gene and its expression in amelogenesis.
AB  - Ameloblastin (also designated amelin and sheathlin) is an enamel matrix protein
      expressed within the ameloblast lineage. In this study we analyzed the structure
      of the rat ameloblastin gene and characterized its subtypes. The promoter
      sequence contains several E-box-like elements, and consensus sequences for AP1
      and SP1. The gene is about 6 kb in length and contains 12 exons. Exon 1 was
      mapped by primer extension and encodes 90 bp of 5' untranslated leader sequence,
      followed by the coding sequences of exon 2 (309 bp), alternatively spliced exon
      3a (45 bp), exon 3b (198 bp), exon 4 (36 bp), exon 5 (60 bp), exon 6 (45 bp),
      exon 7 (150 bp), and exon 8 (448 bp) containing coding sequence (426 bp) and 3'
      untranslated sequence (22 bp), followed by exon 9 (39 bp); exon 10 (143 bp); exon
      11 (342 bp); and exon 12. Exon 3a, encoding YEYSLPVHPPPLPSQ, has a potential SH3
      binding domain. Analysis of ameloblastin subclones showed that exon 3a and 11
      were potential alternative splicing sites, producing 4 types of ameloblastin
      mRNA, from which ameloblastin I and II could be translated. Using in situ
      hybridization, immunohistochemistry, Western blot and RT-PCR methods we found
      that ameloblastin II, containing exon 3a, was more strongly expressed at the late
      maturation stage of ameloblasts than at the secretory stage, while a common probe
      for both ameloblastin subtypes showed wide expression throughout the
      presecretory, secretory and postsecretory stages. From the above results we
      propose that ameloblastin II plays an important role in the mineralization of
      ameloblasts during the maturation stages.

PMID- 12803486
TI  - A Salmonella typhimurium rfaE mutant recovers invasiveness for human epithelial
      cells when complemented by wild type rfaE (controlling biosynthesis of ADP-L
      glycero-D-mannoheptose-containing lipopolysaccharide).
AB  - Invasion of host cells is essential for the pathogenicity of Salmonella. The
      author's group has recently reported the cloning of the rfaE gene of Salmonella
      typhimurium, previously implicated in biosynthesis of the lipopolysaccharide
      (LPS)-inner core [Jin et al. (2001); Kim (2002)]. The product of the rfaE gene is
      involved in ADP-L-glycero-D-manno-heptose biosynthesis. rfaE mutants synthesize
      heptose-deficient LPS (Re-LPS) consisting only of lipid A and 3-deoxy-D-manno
      octulosonic acid (KDO). Mutants that make incomplete LPS are rough mutants and
      "deep-rough" mutants affected in the heptose region of the inner core have
      reduced growth rate and increased sensitivity to high temperature.
      Complementation of S. typhimurium rfaE mutant strain SL1102 (rfaE543) with rfaE
      demonstrated conclusively that this gene restored the smooth phenotype, and the
      LPS produced by the complemented strain was indistinguishable from that of wild
      type smooth strains. In vitro infection experiments showed that complementation
      with rfaE permitted invasion of human Chang epithelial cells, larynx epidermal
      carcinoma HEp-2 cells and intestinal epithelial Henle-407 cells. These data imply
      that the structure of the LPS that is synthesized is critical for Salmonella
      invasiveness.

PMID- 12803487
TI  - The effect of brain-derived neurotrophic factor on neuritogenesis and synaptic
      plasticity in Aplysia neurons and the hippocampal cell line HiB5.
AB  - Brain-derived neurotrophic factor (BDNF) plays a key role in the differentiation
      and neuritogenesis of developing neurons, and in the synaptic plasticity of
      mature neurons, in the mammalian nervous system. BDNF binds to the receptor
      tyrosine kinase TrkB and transmits neurotrophic signals by activating neuron
      specific tyrosine phosphorylation pathways. However, the neurotrophic function of
      BDNF in Aplysia neurons is poorly understood. We examined the specific effect of
      BDNF on neurite outgrowth and synaptic plasticity in cultured Aplysia neurons and
      a multipotent rat hippocampal stem cell line (HiB5). Our study indicates that
      mammalian BDNF has no significant effect on the neuritogenesis, neurotransmitter
      release, excitability, and synaptic plasticity of cultured Aplysia neurons in our
      experimental conditions. In contrast, BDNF in combination with platelet-derived
      growth factor (PDGF) increases the length of the neurites and the number of spine
      like structures in cells of HiB5.

PMID- 12803488
TI  - NADPH dehydrogenase-mediated respiratory electron transport in thylakoid
      membranes of the cyanobacterium Synechocystis sp. PCC 6803 is inactive in the
      light.
AB  - Non-photochemical redox changes of the plastoquinone pools in darkness were
      investigated in the cyanobacterium Synechocystis sp. PCC 6803 by monitoring
      changes in Chl fluorescence yield during light-to-dark transitions. The
      inhibitors rotenone and mercury with or without 1 mM succinate fully suppressed
      the post-illumination increase in Chl fluorescence in both NADPH dehydrogenase
      defective (M55) and deltaCtaI cells. The latter cells lack subunit I of
      cytochrome aa3-type cytochrome c oxidase. These results strongly suggest that
      NADPH dehydrogenase plays the major role in electron donation in the non-photo
      chemical reduction of plastoquinone. The rising phase of post-illumination Chl
      fluorescence in both wild type pretreated with KCN, and deltaCtaI cells, was
      significantly slowed by low light illumination. We detected comparable
      photochemical levels of both photosystem (PS) II and PSI during steady state
      illumination in wild type and deltaCtaI cells. From these results, we suggest
      that respiratory electron flow involved in the non-photochemical redox change of
      plastoquinone is not likely to occur in the light.

PMID- 12803489
TI  - Cbl competitively inhibits epidermal growth factor-induced activation of
      phospholipase C-gamma1.
AB  - Phospholipase C-gamma1 (PLC-gamma1) plays pivotal roles in cellular growth and
      proliferation through its two Src homology (SH) 2 domains and its single SH3
      domain, which interact with signaling molecules in response to various growth
      factors and hormones. However, the role of the SH domains in the growth factor
      induced regulation of PLC-gamma1 is unclear. By peptide-mass fingerprinting
      analysis we have identified Cbl as a binding protein for the SH3 domain of PLC
      gamma1 from rat pheochromatocyte PC12 cells. Association of Cbl with PLC-gamma1
      was induced by epidermal growth factor (EGF) but not by nerve growth factor
      (NGF). Upon EGF stimulation, both Cbl and PLC-gamma1 were recruited to the
      activated EGF receptor through their SH2 domains. Mutation of the SH2 domains of
      either Cbl or PLC-gamma1 abrogated the EGF-induced interaction of PLC-gamma1 with
      Cbl, indicating that SH2-mediated translocation is essential for the association
      of PLC-gamma1 and Cbl. Overexpression of Cbl attenuated EGF-induced tyrosine
      phosphorylation and the subsequent activation of PLC-gamma1 by interfering
      competitively with the interaction between PLC-gamma1 and EGFR. Taken together,
      these results provide the first indications that Cbl may be a negative regulator
      of intracellular signaling following EGF-induced PLC-gamma1 activation.

PMID- 12803490
TI  - Blockade of calcium entry accelerates arsenite-mediated apoptosis in rat
      cerebellar granule cells.
AB  - Arsenical exposure can cause defects in the central nervous system, yet the
      underlying cellular and molecular mechanisms are largely unknown. We have
      recently demonstrated that sodium arsenite induces apoptosis of cultured cortical
      and cerebellar neurons, suggesting that arsenite-induced neuronal apoptosis may
      contribute to at least some of its neurotoxic effects. Here we investigated the
      effect of Ca2+ on arsenite-mediated cerebellar granule neuron death. Sodium
      arsenite induced apoptosis in cerebellar neurons which were maintained in the
      presence of serum and depolarizing concentrations of potassium chloride (25 mM
      KCI). Under these conditions, inhibition of calcium entry by N-methyl-D-aspartate
      (NMDA) receptor blocker DL-aminophosphonovalerate (APV) or calcium channel
      antagonist nifedipine increased arsenite-induced apoptosis, while APV or
      nifedipine alone had little effect on cell viability. In cortical neurons or
      cerebellar neurons maintained at low potassium (5 mM), arsenite also induced
      apoptosis. However, the addition of APV or nifedipine did not alter levels of
      arsenite-induced apoptosis. These data suggest that arsenite-mediated apoptosis
      is regulated by intracellular calcium levels.

PMID- 12803491
TI  - Angiogenesis and white blood cell proliferation induced in mice by injection of a
      prolactin-expressing plasmid into muscle.
AB  - Prolactin (PRL) is a pituitary hormone involved in a broad spectrum of
      physiological processes, including lactation, development, and immune function.
      To further investigate the in vivo roles of PRL, rat PRL cDNA, fused to the
      cytomegalovirus promoter, was introduced into mouse muscle by direct injection.
      Prolactin mRNA and protein were detected in the muscle following injection. As a
      result the number of white blood cells (WBC) increased. When injection was
      combined with adrenalectomy there was an even greater increase. The augmentation
      of WBCs persisted for at least 20 days after injection of the rPRL plasmid either
      on its own and after injection combined with adrenalectomy. The increase in WBCs
      was accompanied in both cases by an increase in blood cell DNA content. We also
      observed an increase in heart volume, particularly of the left ventricle.
      Evidence of marked angiogenesis was found in the testis of rPRL- injected mice.
      New blood vessels were first found at 8 weeks of age and fully developed blood
      vessels with complex branching patterns were found after 11 weeks. When PRL fused
      with EGFP was introduced into mice by intramuscular injection, the EGFP localized
      to areas of the testis that corresponded to the sites of new blood vessel
      formation. PRL inhibited this binding. Taken together, our data reveal that
      intramuscularly expressed PRL augments WBC numbers and induces formation of new
      blood vessels in the testis, suggesting important roles for PRL in hematopoiesis
      and angiogenesis. They also indicate that direct intramuscular injection of naked
      DNA can be used effectively to study the function of secreted proteins, including
      endocrine signaling molecules.

PMID- 12803492
TI  - Cellular localization of pituitary adenylate cyclase-activating polypeptide in
      the rat testis.
AB  - Several growth factors are critical regulators of testicular development.
      Recently, pituitary adenylate cyclase-activating polypeptide (PACAP) has been
      shown to promote the differentiation and proliferation of various cell types and
      to stimulate the release of vascular endothelial growth factor during tissue
      growth. The present study aimed to evaluate the possible expression of PACAP in
      immature and adult rat testes by Northern blot analysis, in situ hybridization,
      and immunohistochemistry. PACAP transcripts were detected in both immature and
      adult tissues, but the level of PACAP expression depended on the age of the
      animal. It was expressed in the peritubular and interstitial cells of the 14-day
      old testis and in seminiferous tubules of the 90-day-old-testis. It was strongly
      expressed in blood vessels at 14 days, moderately at 28 days and only weakly at
      90 days. These results suggest that PACAP contributes to the growth and
      differentiation of peritubular and interstitial cells, and of blood vessels,
      during testicular development.

PMID- 12803493
TI  - Chloroplast inheritance patterns in Actinidia hybrids determined by single
      stranded conformation polymorphism analysis.
AB  - The inheritance patterns of the chloroplast genomes of the Actinidia hybrids A.
      eriantha (male parent) x A. chinensis (female parent) and A. chinensis (male
      parent) x A. melanandra (female parent) were analyzed using single-strand
      conformation polymorphism (SSCP) analysis of the trnL-trnF and psbA-trnH
      intergenic spacers. This showed that the artificial hybrids between A. eriantha
      and A. chinensis all had the haplotype of their male parent. Alignment of the
      sequences of A. eriantha and A. chinensis revealed four substitutions and one
      insertion (GATTC) in trnL-trnF and two substitutions in psbA-trnH. In contrast,
      the haplotypes of the artificial hybrids between A. chinensis and A. melanandra
      had the same patterns as their female parent. Alignment of the entire region of
      A. chinensis and A. melanandra revealed 12 substitutions: 1 in trnL-trnF and 11
      in psbA-trnH. However, no sequence variation in the trnL-trnF and psbA-trnH
      intergenic spacers was found. We have developed a simple screening method for
      detecting the inheritance patterns of Actinidia chloroplast DNA haplotypes using
      SSCP analysis of the trnL-trnF and psbA-trnH intergenic spacers. Our findings
      indicate that the inheritance of the chloroplast genome in Actinidia hybrids
      differs according to the species selected.

PMID- 12803494
TI  - Dissecting the role of peptides in the immune response: theory, practice and the
      application to vaccine design.
AB  - Analytical biochemistry and synthetic peptide based chemistry have helped to
      reveal the pivotal role that peptides play in determining the specificity,
      magnitude and quality of both humoral (antibody) and cellular (cytotoxic and
      helper T cell) immune responses. In addition, peptide based technologies are now
      at the forefront of vaccine design and medical diagnostics. The chemical
      technologies used to assemble peptides into immunogenic structures have made
      great strides over the past decade and assembly of highly pure peptides which can
      be incorporated into high molecular weight species, multimeric and even branched
      structures together with non-peptidic material is now routine. These structures
      have a wide range of applications in designer vaccines and diagnostic reagents.
      Thus the tools of the peptide chemist are exquisitely placed to answer questions
      about immune recognition and along the way to provide us with new and improved
      vaccines and diagnostics.

PMID- 12803495
TI  - Alpha-aminoxy acids as building blocks for the oxime and hydroxylamine
      pseudopeptide links. Application to the synthesis of human elastase inhibitors.
AB  - The aminoxy acids NH2-O-C(alpha)HR-CO2H are much more easily obtained in the
      enantiomerically pure form than the analogous hydrazino acids NH2-NH-C(alpha)HR
      CO2H, and it has been shown that the isosteric amidoxy psi[CO-NH-O] and hydrazide
      psi[CO-NH-NH] amide surrogates Induce two quite similar gamma-like folded
      structures. An aminoxy acid can also be N-coupled to a peptide aldehyde to give
      the aldoxime psi[CH = N-O] link or to a peptide ketone to form the ketoxime
      psi[CR= N-O] link. The former can be further reduced into the hydroxylamine
      psi[CH2-NH-O] link which gives rise to reduced amidoxy peptides. The structural
      properties Induced by these amide surrogates were studied, using IR and NMR
      spectroscopy, paying particular attention to the Z/E-isomerism of the oxime link.
      In order to investigate their inhibitory potency, the three amide surrogates were
      introduced in the Pro3-Val4 and Val4-Ala5 position of Z-Ala1-Ala2-Pro3-Val4-Ala5
      Ala6-NHiPr, a substrate which is cleaved in the Val4-Ala5 position by human
      leukocyte elastase (HLE). The [Val4psi[CO-NH-O]Ala5] analogue was still a
      substrate, while the [Pro3psi[CO-NH-O]Val4] and [Val4psi[CH = N-O]Ala5]
      pseudopeptides acted as HLE competitive inhibitors.

PMID- 12803496
TI  - Antitumour activity and specificity as a function of substitutions in the
      lipophilic sector of helical lactoferrin-derived peptide.
AB  - A peptide L5 (PAWRKAFRWAWRMLKKAA), derived from the N-terminal alpha-helical
      region of bovine lactoferrin (LFB 14-31), that is highly active against several
      tumour cell lines was reported earlier. In this study, a number of L5 analogues
      were designed in order to investigate how subsequent replacements of the aromatic
      amino acids in L5 with three amino acids representing different structural
      parameters influenced antitumour activity and tumour cell specificity relative to
      normal human cells. The Trp residues were substituted by Lys, Ile or Ala, while
      the Phe residue was substituted with Ala. The resulting peptides were
      investigated for their activity against prokaryotic cells, four tumour cell
      lines, human lung fibroblasts and human erythrocytes. Most of the peptides were
      highly active against both E. coli and S. aureus. The peptides were more active
      against the tumour cell lines than against normal eukaryotic cells but the
      activity against normal fibroblasts varied more among the peptides than did their
      antitumour activities. The results revealed that aromatic residues located
      opposite the cationic sector in L5 were more critical for antitumour activity
      than were aromatic residues located adjacent to the cationic sector. The
      biological responses for the peptides against tumour cell lines, fibroblasts, S.
      aureus (but not E. coli), were highly correlated with the amino acid descriptors
      used in our QSAR model. The result obtained from the QSAR study identified
      specific structural features that were important for lytic activity and membrane
      specificity. Certain structural properties in positions 3, 9 and 11 were shown to
      be important for antitumour activity, while additional structural properties in
      position 7 were found to be important with respect to tumour cell specificity.
      This information may offer a possibility for de novo design of an antitumour
      peptide with an improved therapeutic index.

PMID- 12803497
TI  - Efficient protocols for the synthesis of enantiopure gamma-amino acids with
      proteinogenic side chains.
AB  - The synthesis of enantiopure gamma-substituted gamma-amino acids with
      proteinogenic side chains, starting from the corresponding natural alpha-amino
      acids, was studied. N-Protected amino aldehydes containing various protective
      groups were prepared from the corresponding amino alcohols by oxidation with
      NaOCl in the presence of AcNH-TEMPO and directly reacted with methyl, benzyl and
      tert-butyl phosphoranylidene acetate to produce alpha,beta-unsaturated gamma
      amino esters. Simultaneous hydrogenation of the double bond and removal of either
      the benzyl or benzyloxycarbonyl group led to N- or C-protected gamma-amino acids
      in high yield. The enantiomeric purity was studied by 1H NMR analysis of Mosher
      amides and chiral HPLC analysis.

PMID- 12803498
TI  - HCV induced renal disease.

PMID- 12803499
TI  - The role of growth factors on renal tubular cells submitted to hypoxia and
      deprived of glucose.
AB  - BACKGROUND: In acute renal failure (ARF) renal tubular cell death and detachment
      can be induced by necrotic and apoptotic mechanisms. Several studies have
      demonstrated some benefits of the use of growth factors in experimental models of
      ARF. METHODS: MDCK cells were cultured in a glucose-free medium for 24h and were
      submitted to hypoxia (PO2 around 35 mmHg) for additional 24 h. To evaluate the
      possible protective role of growth factors, EGF, IGF-I or HGF were added to the
      medium (20 ng mL). LDH release, viability (acridine orange and ethidium bromide
      dyes) and quantification of apoptotic cells (Hoechst 33342 dye fluorescence) were
      determined. RESULTS: In the injury group, an increase on LDH release (60% vs. 3%)
      and on number of apoptotic cells (22% vs. 0.2%) which was associated with a
      reduced cell viability (61% vs. 94%) when compared with controls. Only HGF, not
      EGF or IGF-I, was able to protect cells from injury. HGF caused a significant
      reduction on LDH release (30%) and on number of apoptotic cells (5%), with an
      increase on viability cellular (79%). CONCLUSIONS: HGF decreases cell death on
      MDCK cells after hypoxic-induced injury, probably acting in both necrotic and
      apoptotic mechanisms.

PMID- 12803500
TI  - Early manifestation of nephropathy in rats with arterial calcinosis.
AB  - In vascular smooth muscle, calcium overload is a highly pathogenic event, which
      increases with advancing age. An increase in the calcium content of arterial wall
      may be produced in rats by treatment with vitamin D3. The aim of this study was
      to evaluate the renal clearance of sulfanilamide (a model organic anion,
      preferentially eliminated by the kidneys) and other parameters of global renal
      function in rats with arterial calcinosis. Arterial calcinosis was produced in
      adult rats by means of a single dose of vitamin D3 (300,000 UI/kg bw, i.m.) 5
      days before the experiment. Treated rats showed a large increase in calcium
      content of aortic tissue and an increase in systolic arterial pressure. No
      modifications were observed in plasma calcium levels and in plasma lipid
      profiles. Statistically significant decrements were observed in renal clearance
      of sulfanilamide, in renal blood flow, in fractional excretion of sodium and
      potassium. A slight decrease, not statistically different, was observed in the
      glomerular filtration rate. Rats with arterial calcinosis also showed an
      increment of total calcium levels in renal tissue, in fractional excretion of
      calcium and in the expression of organic anion transporter 1 (OAT1). Histological
      studies revealed tubular alterations. In summary, modifications in hemodynamics
      and tubular parameters are early manifestations of nephropathy in rats with
      arterial calcinosis, some of which may account for the changes observed in
      organic anions renal depuration. It is important to mention that the decrease in
      clearance of organic anions were seen in spite of the increase in expression of
      OAT1.

PMID- 12803501
TI  - Prophylactic effect of lipoic acid against adriamycin-induced peroxidative
      damages in rat kidney.
AB  - Adriamycin (ADR), which is widely used in the treatment of various neoplastic
      conditions, exerts toxic effects in many organs. The present study was designed
      to investigate the effect of lipoic acid (LA) against acute ADR induced
      peroxidative damages in rat kidney. The study was carried out with adult male
      albino rats of Wistar strain, which comprised of one control and three
      experimental groups. Group I rats served as controls. Group II rats received ADR
      (7.5mg/kg body weight) intravenously through the tail vein. Group III rats were
      given LA (75 mg/kg body weight) intraperitoneally. Group IV rats were given LA
      one day before the administration of ADR. Rats subjected to ADR administration
      showed a decline in the thiol capacity of the cell accompanied by high
      malondialdehyde (MDA) levels along with lowered activities of catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GPx) glutathione (GSH) and
      GSH metabolizing enzymes (glutathione reductase (GR), glucose-6-phosphate
      dehydrogenase (G6PD)). However no significant change was observed in the activity
      of glutathione-S-transferees (GST). Pretreatment with LA showed considerable
      changes over oxidative stress parameters. Nephrotoxic damage was evident from the
      decrease in the activities of gamma-glutamyl transferase (gamma-GT) and beta
      glucuronidase (beta-GLU), which were reverted upon LA pretreatment. CONCLUSION:
      This study has highlighted the beneficial effects of LA pretreatment in reversing
      the damages caused by ADR, by bringing about an improvement in the reductive
      status of the cell.

PMID- 12803502
TI  - Repetitive brief ischemia: intermittent reperfusion during ischemia ameliorates
      the extent of injury in the perfused kidney.
AB  - Acute renal failure commonly follows reduced renal perfusion or ischemia.
      Reperfusion is essential for recovery but can itself cause functional and
      structural injury to the kidney. The separate contributions of ischemia and of
      reperfusion were examined in the isolated perfused rat kidney. Three groups were
      studied: brief (5 min) ischemia, 20 min ischemia, and repetitive brief ischemia
      (4 periods of 5 min) with repetitive intervening reperfusion of 5 min. A control
      group had no intervention, the three ischemia groups were given a baseline
      perfusion of 30 min before intervention and all groups were perfused for a total
      of 80 min. In addition, the effects of exogenous *NO from sodium nitroprusside
      and xanthine oxidase inhibition by allopurinol were assessed in the repetitive
      brief ischemia-reperfusion model. Brief ischemia produced minimal morphological
      injury with near normal functional recovery. Repetitive brief ischemia
      reperfusion caused less functional and morphological injury than an equivalent
      single period of ischemia (20 min) suggesting that intermittent reperfusion is
      less injurious than ischemia alone over the time course of study. Pretreatment
      with allopurinol improved renal function after repetitive brief ischemia
      reperfusion compared with the allopurinol-untreated repetitive brief ischemia
      reperfusion group. Similarly, sodium nitroprusside reduced renal vascular
      resistance but did not improve the glomerular filtration rate or sodium
      reabsorption in the repetitive brief ischemia-reperfusion model. Thus, these
      studies show that the duration of uninterrupted ischemia is more critical than
      reperfusion in determining the extent of renal ischemia-reperfusion injury and
      that allopurinol, in particular, counteracts the oxidative stress of reperfusion.

PMID- 12803503
TI  - Scrub typhus: a frequently overlooked cause of acute renal failure.
AB  - Acute renal failure associated with scrub typhus infection is not rare as
      previously thought. The possibility of scrub typhus should be borne in mind when
      patients present with fever and varying degrees of acute renal failure,
      particularly if an eschar exists, along with a history of environmental exposure
      in an area like Taiwan, where scrub typhus is endemic. Prompt diagnosis and the
      use of appropriate antibiotics can rapidly alter the clinical course of the
      disease and prevent the development of serious or fatal complications. To
      illustrate the above point, this study reports 3 cases of scrub typhus associated
      with acute renal failure. They were seen at Chang Gung Memorial Hospital in a 2
      year interval. Case 1 was referred from district hospital with clinical features
      of multiple organ dysfunctions, including shock, fever, acute respiratory
      failure, acute renal failure, and acute hepatitis. Case 2 was admitted with the
      chief problems of shock, fever, acute renal failure, and DIC. Case 3 visited our
      outpatient clinic due to fever, maculopapular rash and acute renal failure. In
      all these patients, the diagnosis was confirmed using immunofluorescence
      techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or
      greater. Notably, despite having varying degrees of acute renal deterioration,
      the patients responded very well to doxycycline therapy and recovered completely.
      Additionally, a total of 4 similar cases of scrub typhus associated with acute
      renal failure were reviewed from the past literature.

PMID- 12803505
TI  - Effect of membrane composition on cytokine production and clinical symptoms
      during hemodialysis: a crossover study.
AB  - BACKGROUND: Intradialytic symptoms including hypotension have been reported
      during dialysis and it has been suggested that these are related to the release
      of cytokines like IL-1beta and TNFalpha by blood mononuclear cells when they get
      activated either due to contact with the dialyzer membrane or by compliment
      activation. OBJECTIVE: To study the relationship between hemodialysis symptoms,
      cytokine production, and dialyzer membrane composition. METHOD: In a randomized
      prospective crossover study, 20 ESRD patients on maintenance hemodialysis were
      studied over cuprophan (CU) and polysulfone (PS) low flux dialyzer membranes for
      three weeks each undergoing a biweekly dialysis schedule of 4 h sessions. Serial
      IL-1beta and TNFalpha levels were measured over 0, 15, 240 min during the first
      use of the dialyzer for all patients on both membranes. Intradialytic symptoms
      were monitored in a total of 240 dialysis sessions. RESULTS: IL-1beta levels
      increased from 16.6 +/- 2.2 to 64.8 +/- 25.1 pg/mL on CU and 21.5 +/- 3.7 to
      103.5 +/- 30.7 pg/mL on PS membrane over the 4-h dialysis session. Similarly
      TNFalpha increased from 42.8 +/- 4.5 to 354.9 +/- 80.4 pg/mL on CU and 117.1+/-
      53.7 to 387.0 +/- 78.0 pg/mL on PS membrane. IL-1beta levels increased
      significantly with PS membrane while TNFalpha rise was significant with both the
      membranes. Nausea was the most common symptom occurring in 138 dialysis sessions
      (57.5%). Vomiting, chest pain, fever, chills, and breathlessness occurred
      significantly more during dialysis with CU membrane as compared with PS membrane
      (P < 0.01). Nausea, cramps, back pain, itching, restlessness, post dialysis
      fatigue, and hypotension did not differ between the two membranes. The mean rise
      in the cytokine levels during the first 15 min of sessions where the symptoms
      occurred, when compared with the mean rise in sessions where the symptoms did not
      occur, did not reveal any significant difference. Cytokine release did not
      correlate with the occurrence of intradialytic symptoms. CONCLUSION: Both CU and
      PS membranes increase circulating cytokine levels. More intradialytic clinical
      symptoms are seen in dialysis with CU as compared with PS membrane but the rise
      in cytokines IL-1beta and TNFalpha does not appear to be responsible for them.

PMID- 12803504
TI  - Lipid profile before and after renal transplantation--a longitudinal study.
AB  - BACKGROUND: The data on lipid profile in renal transplant recipients from the
      Indian subcontinent is scant. METHODS: Lipid profile was studied in 30
      consecutive patients of end stage renal disease before renal transplantation (0
      month) and prospectively posttransplantation at 1, 3, and 6 months. The results
      were compared with 30, age and sex matched, healthy controls. All the patients
      received triple immunosuppression (prednisolone, azathioprine and cyclosporine).
      RESULTS: Pretransplantation, the hypertriglyceridemia and hypercholesterolemia
      was present in 20% and 7% of the patients and the difference (elevation) in the
      mean values of various lipid fractions was not significant compared to healthy
      controls except a fall in HDL (p < .01). After renal transplantation, there was a
      significant elevation in the mean values of total cholesterol, triglycerides,
      VLDL, and LDL cholesterol at 1, 3, and 6 months. HDL cholesterol levels remained
      significantly lower as compared to healthy controls. Although, the mean values of
      serum triglycerides and cholesterol were significantly higher in diabetic end
      stage renal disease compared to nondiabetic ESRD, however there was insignificant
      difference in the lipid profile amongst diabetic and nondiabetic renal allograft
      recipients. CONCLUSION: Our data shows distinct elevation in the lipids and
      lipoproteins after renal transplantation and immunosuppressive drugs seem to be
      the culprit.

PMID- 12803506
TI  - Using cuffed and tunnelled central venous catheters as permanent vascular access
      for hemodialysis: a prospective study.
AB  - BACKGROUND: Adequate care of a hemodialysis patient requires constant attention
      to the need to maintain vascular access (VA) patency. VA complications are the
      main cause of hospitalization in hemodialysis patients. The native arteriovenous
      fistula (NAVF), synthetic arteriovenous grafts fistula (GAVF) and silastic cuffed
      central venous catheters (CVCs) are used for permanent vascular access (PVA).
      CVCs are primary the method of choice for temporary access. But using this access
      modality is increasing more and more for PVA in elderly hemodialysis patients and
      when other PVA is not possible. The primary aim of this study is to investigate
      survivals and complications of the CVCs used for long-term VA. METHODS: We
      prospectively looked at 92 CVCs (Medcomp Ash Split Cath, 14 FR x 28 cm (Little,
      M.A.; O'Riordan, A.; Lucey, B.; Farrell, M.; Lee, M.; Conlon, P.J.; Walshe, J.J.
      A prospective study of complications associated with cuffed, tunnelled
      hemodialysis catheters. Nephrol. Dial. Transplant. 2001, 16 (11), 2194-2200) with
      Dacron cuff) inserted in 85 (50 females, 35 males) chronic hemodialysis patients
      (the mean age: 56.6 +/- 14.1 years) from July 1999 to January 2002. The overall
      survival and complications were followed up. Furthermore, the patients were
      evaluated for demographic and clinical characteristics. Data were analysed by chi
      square, Wilcoxon rank and Kaplan-Meier survival tests. RESULTS: The median
      duration of CVC survival was 289 days (range: 10-720). Eleven (11.9%) CVCs were
      removed due to complications. In 79 (92.9%) patients, 1, in 5 (5.8%) patients, 2
      and in 1 patient, 3 CVCs were inserted. Of the 85 patients, 56 have CVCs
      functioning. In addition, 27 (31.76%) patients have CVCs functioning for over 12
      months, 17 (20%) patients have CVCs functioning for 6 months. The total incidence
      of CVC related infections was 0.82 episodes/1000 catheter days. Besides,
      thrombosis was occurred in 10 (10.8%) CVCs. The most frequent indications for CVC
      removal were patient death (69.4%), thrombosis (16.6%) and CVC-related infections
      (13.8%). CONCLUSIONS: CVCs are primarily used for temporary access. But this
      study indicates that CVC may be a very useful alternative permanent vascular
      access for hemodialysis patients when other forms of vascular access are not
      available.

PMID- 12803507
TI  - Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric
      renal diseases.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is produced mainly
      by tubular epithelial cells in kidney and contributes to renal interstitial
      inflammation and fibrosis. More recently, we have demonstrated that urinary MCP-1
      excretion is increased in proportion to the degree of albuminuria (proteinuria)
      and positively correlated with urinary N-acetylglucosaminidase (NAG) levels in
      type 2 diabetic patients. Based on these findings, we have suggested that heavy
      proteinuria, itself, probably aggravates renal tubular damage and accelerates the
      disease progression in diabetic nephropathy by increasing the MCP-1 expression in
      renal tubuli. In the present study, to evaluate whether urinary MCP-1 excretion
      is increased in the proteinuric states not only in diabetic nephropathy but also
      in other renal diseases, we examined urinary MCP-1 levels in IgA nephropathy
      patients with macroalbuminuria (IgAN group; n = 6), and compared the results with
      the data obtained from type 2 diabetic patients with overt diabetic nephropathy
      (DN group; n = 23) and those without diabetic nephropathy (non-DN group; n = 27).
      Urinary MCP-1 excretion levels in non-DN, DN, IgAN groups were 157.2 (52.8
      378.5), 346.1 (147.0-1276.7), and 274.4 (162.2-994.5) ng/g creatinine, median
      (range), respectively. Expectedly, urinary MCP-1 and NAG excretion levels in DN
      and IgAN groups were significantly elevated as compared with non-DN group.
      Therefore, we suggest that MCP-1 expression in renal tubuli is enhanced in
      proteinuric states,irrespective of the types of renal disease, and that increased
      MCP-1 expression probably contributes to renal tubular damage in proteinuric
      states.

PMID- 12803509
TI  - Improvement of clinical outcome by early nephrology referral in type II diabetics
      on hemodialysis.
AB  - OBJECTIVES: To evaluate the influence of early nephrology referral on clinical
      outcome in type II diabetes mellitus patients on maintenance hemodialysis
      dialysis. PATIENTS AND METHODS: This study retrospectively analyzed the type II
      diabetic patients entering our PD program from February 1988 to June 2001.
      Patients who were presented to a nephrologist more than 6 months before starting
      dialysis were defined as early referral (ER). Patients were considered late
      referral (LR) if they were transferred to the nephrology department within 6
      months before initial dialysis. RESULTS: Hundred and fifteen type II diabetic
      patients receiving HD for at least 3 months were enrolled in this study. Sixteen
      of the 53 patients (46.1%) were in the ER group and 62 of the 115 (53.9%) were in
      the LR group. In univariate analysis by Cox proportional hazards mode, the early
      referral (Exp (Coef) = 0.423, p < 0.01), good glycemic control (Exp (Coef) =
      0.16, p < 0.05), and age at dialysis (Exp (Coef) = 1.026, p < 0.05 (had
      significantly influenced the patient survival. The residual renal function in the
      ER group, estimated by creatinine clearance (Ccr), significantly exceeded that of
      the LR group (ER vs. LR: 4.46 +/- 1.56 vs. 2.51 +/- 1.70 mL/min, p < 0.001). The
      patients with early referral had significantly better survival (p < 0.05). Five
      year survival improved significantly in the early referral group compared to the
      late referral group (ER: 72.4%; LR: 35.2%, p < 0.05). CONCLUSIONS: We demonstrate
      that the time of referral before starting dialysis is a predictor of survival for
      type II diabetics on HD. Patients with early referral are associated with longer
      survival. The beneficial effect might be associated with the timely initiation of
      the chronic HD program. These results suggest that early referral before dialysis
      is important in determining the long-term prognosis in type II diabetics on HD.

PMID- 12803508
TI  - Low dose intravenous ascorbic acid for erythropoietin-hyporesponsive anemia in
      diabetic hemodialysis patients with iron overload.
AB  - BACKGROUND: Recent report demonstrates that inadequate iron mobilization and
      defective iron utilization may cause recombinant erythropoieitin (rEPO)
      hyporesponsiveness in hemodialysis (HD) patients with iron overload. The effect
      of intravenous ascorbic acid (IVAA) in HD patients selected on the basis of iron
      overload and EPO resistance also has been proven. However, it is uncertain
      whether IVAA still works in diabetic ESRD patients with hyperferritinemia.
      Therefore, the aim of this study focusing on diabetic ESRD patients was to
      analyze the potential effect of low dose IVAA on improvement of anemia and
      erythropoiesis-related parameters when compared with control period. PATIENTS AND
      METHOD: This study consisted of 22 chronic hemodialysis patients with type II
      diabetes in a single dialysis unit. In studies of this type, all eligible
      patients are followed up, but the primary comparison is still between different
      sequentially treatment including control period and post-IVAA period in same
      patients. IVAA patients received ascorbic acid, 100 mg each administered
      intravenously three times per week for eight weeks of treatment and four months
      of post-treatment follow-up. RESULTS: The demographic characteristics of 22
      diabetic uremic patients show that mean age is 63.6 +/- 10.2 years old. The ratio
      of sex (M/F) = 10/12. Mean duration of HD is 46.7 +/- 33.2 months. As for the
      urea kinetic study between these two periods including KT/V, nPCR, and URR, there
      is no significantly different. As for anemia-related parameters, Hb and Hct
      increased significantly in post-IVAA period after 3 months compared with control
      period, while MCV did not increase significantly. Serum ferritin significantly
      decreased at study completion. The same situation is for iron. As for TS, it
      significantly increased at one month and further markedly increased at subsequent
      three months. CONCLUSION: This study has demonstrated that short-term low dose
      IVAA therapy can facilitate iron release from reticuloendothelial system but also
      increase iron utilization in diabetic hemodialysis patients with iron overload.
      Therefore, IVAA is a potential adjuvant therapy to treat erythropoeitin
      hyporesponsive anemia in iron-overloaded patients.

PMID- 12803510
TI  - Combination of pentoxifylline with angiotensin converting enzyme inhibitors
      produces an additional reduction in microalbuminuria in hypertensive type 2
      diabetic patients.
AB  - OBJECTIVE: To investigate the anti proteinuric effect of pentoxifylline in
      diabetic patients, we prospectively studied in 25 hypertensive type 2 diabetic
      patients with persistent microalbuminuria and normal renal function the impact of
      combining pentoxifylline with an angiotensin converting enzyme inhibitor,
      lisinopril, on urinary albumin excretion and compared the results with those
      obtained in a control group of 25 type 2 diabetic patients treated with
      lisinopril only. MATERIAL AND METHODS: Fifty hypertensive type 2 diabetic
      patients with persistent microalbuminuria (31 males and 19 females, aged between
      47-73 years) were randomly assigned to two groups. Group A received lisinopril 10
      mg/day, while group B was given lisinopril 10 mg/day and pentoxifylline 600
      mg/day for nine months. There were no significant differences between serum
      creatinine, HbA1c, blood pressure and urinary albumin excretion in both groups (p
      > 0.05). RESULTS: Serum creatinine, creatinine clearance, blood pressure, HbA1c
      levels did not change significantly during the study. Urinary albumin excretion
      decreased from 228 +/- 28 to 148 +/- 15 mg/day in group A (p < 0.05). In group B
      urinary albumin excretion decreased from 219 +/- 26 to 128 +/- 12 mg/day (p <
      0.05). Pentoxifylline and lisinopril combination caused a significant additional
      reduction in urinary albumin excretion when compared to lisinopril regimen (p <
      0.05). CONCLUSIONS: Our findings suggest that the combination of pentoxifylline
      with an angiotensin converting enzyme inhibitor in hypertensive type 2 diabetic
      patients with persistent microalbuminuria causes a significant reduction in
      urinary albumin excretion and this effect seems independent from blood pressure
      and glycemic control.

PMID- 12803512
TI  - Glomerular endothelial dysfunction and hemodynamic maladjustment in
      vesicoureteric reflux.
AB  - A structural defect of the non-vascular component of a nephron namely
      vesicoureteric reflex (VUR) can induce injury to the vascular component, which is
      reflected by the alteration in intrarenal hemodynamics. A mild alteration in
      intrarenal hemodynamics was observed in grades I-II VUR which revealed (a) mild
      reductions in renal plasma flow (RPF) 543 +/- 104 mL/min/1.73 m2; in peritubular
      capillary flow (PTCF) 438 +/- 103mL/min/1.73 m2; in glomerular filtration rate
      (GFR) 105 +/- 19 mL/min/1.73 m2 and in ultrafiltration coefficient (KFG) 0.04 +/-
      0.01 mL/s/mmHg; (b) normal values of filtration fraction (FF) 0.2 +/- 0.04, of
      intraglomerular hydrostatic pressure (PG) 50 +/- 0.3 mmHg, and of afferent
      arteriolar resistance (RA) 2261 +/- 718 dyne s cm(-5); and (c) a slight elevation
      of efferent arteriolar resistance (RE) 3914 +/- 962 dyne s cm(-5). In contrast, a
      moderately severe alteration in intrarenal hemodynamics was observed in severe
      VUR (grades III up) which revealed greater reductions in RPF 267 +/- 114
      mL/min/1.73 m2, in PTCF 195 +/- 90 mL/min/1.73 m2, in GFR 72 +/- 34 mL/min/1.73
      m2 and in KFG 0.03 +/- 0.01 mL/s/mmHg; and elevation of PG 53 +/- 2 mmHg, of
      filtration fraction 0.27 +/- 0.07, of RA 4557 +/- 2340 dyne s cm(-5) and of RE
      9417 +/- 4163 dyne s cm(-5). Such an alteration in intrarenal hemodynamics
      observed in severe VUR induces both intraglomerular hypertension (elevated PG)
      and an exaggeratedly reduced PTCF. This intrarenal hemodynamic defect is due to
      the glomerular endothelial dysfunction and its hemodynamic maladjustment. In
      accordance with the preceding information, treatment to correct the hemodynamic
      maladjustment is likely to improve renal function and prevent renal disease
      progression.

PMID- 12803511
TI  - The effect of erythropoietin therapy and hemoglobin levels on the immune response
      to Engerix-B vaccination in chronic kidney disease.
AB  - BACKGROUND: Patients undergoing chronic hemodialysis have an increased risk of
      acquiring hepatitis B infection. Only 43-66% of dialysis patients develop
      effective anti-HBs titers after vaccination. AIM: To evaluate the effect of
      recombinant erythropoietin (rEPO) therapy and basal hemoglobin levels on the
      outcome of the immune response to four doses of IM 40 microg Engerix-B
      vaccination in hemodialysis and chronic kidney disease (CKD) patients before
      starting replacement therapy. SUBJECTS AND METHODS: One hundred and three
      patients were included in the study: 34 hemodialysis patients treated with rEPO
      (Group A), 36 predialytic patients who did not treated with rEPO (Group B) and 33
      predialytic patients treated with rEPO (Group C). Plasma creatinine in
      predialytic patients was 2-7 mg/dL. All patients' HBsAg and anti-HBs antibodies
      were negative. Patients were immunized with IM 40 microg Engerix-B at 0, 1, 3,
      and 6 months. Anti-HBs titers were measured at 7th month. RESULTS: Eighty seven
      point one percent of patients from group C developed protective anti-HBs titers
      compared with 69.4% from group B and 44.1% from group A (p = 0.001). Patients
      from all groups with baseline hemoglobin levels above 11 gr/dL developed
      protective anti-HBs titers significantly more than patients with baseline
      hemoglobin levels below 11 gr/dL (p < 0.05). CONCLUSION: Predialytic patients
      treated with rEPO and with hemoglobin levels higher than 11 gr/dL had
      significantly better immune response outcomes to Engerix-B vaccination.
      Immunization against hepatitis B infection should be considered at early stages
      of CKD prior to the deterioration in kidney functions and the development of
      renal anemia.

PMID- 12803513
TI  - Adrenal insufficiency due to isolated adrenocorticotropin deficiency complicated
      by autosomal recessive polycystic kidney disease.
AB  - We describe a 29-old-year Japanese man with autosomal recessive polycystic kidney
      disease who was frequently hypoglycemic. Insulinoma as a cause of hypoglycemia
      was denied because the ratio of plasma immunoreactive insulin to glucose was low.
      Adrenal insufficiency was diagnosed because of the low urinary excretion of 17
      hydroxycorticosteroids, and both blunted responses of plasma cortisol to an
      intravenous injection of adrenocorticotropin and of plasma adrenocorticotropin to
      an intravenous injection of human corticotropin releasing hormone were observed,
      although basal plasma concentrations of cortisol and adrenocorticotropin were
      normal. The elusion profile of plasma sample from our patient chromatographed on
      a Sephadex G-75 column showed two peaks of (1-39)-ACTH and beta-lipotropin, with
      no evidence of high molecular weight form of ACTH. The plasma concentrations of
      thyroid stimulating hormone and growth hormone were within the normal range.
      These findings indicated that this patient with autosomal recessive polycystic
      kidney disease was associated with adrenal insufficiency due to isolated
      adrenocorticotropin deficiency.

PMID- 12803514
TI  - Staphylococcal pericarditis in a chronic renal failure patient.
AB  - A 34-year-old female with end-stage renal disease was admitted for severe
      metabolic acidosis, uremic encephalopathy, pericarditis and severe anemia
      following a bout of acute gastroenteritis. She improved on aggressive medical
      management including intensive hemodialysis and was initiated onto maintenance
      heparin-free hemodialysis (twelve hours per week) and discharged. After a week,
      she presented with fever with chills and rigors for three days, was toxic,
      severely orthopenic and had a pulsus paradoxus of 36 mmHg. Echocardiography
      suggested cardiac tamponade. Aspiration revealed frank pus with polymorphonuclear
      predominance and Staphylococcus aureus on culture. CT of the thorax revealed
      pericardial effusion. In the absence of any obvious septic foci, concomitant
      pleuro-pulmonary sepsis, mediastinal or intra-abdominal pathology; a diagnosis of
      "acute primary purulent pericarditis" was made. Patient was put on parenteral
      antibiotics-ceftriaxone and metrogyl. Vancomycin was added after sensitivity
      results. Pericardial drainage was required initially. After toxemia improved,
      paradox decreased and fever subsided, the pericardial catheter was removed and
      antibiotics continued for a period of four weeks. Maintenance hemodialysis was
      continued during hospital stay and after discharge.

PMID- 12803515
TI  - Refractory hypertension and anemia in end-stage renal disease: an unusual
      manifestation of Kimura's disease.
AB  - Hypertension and anemia are common in uremic patients. This article describes a
      35-year-old uremic Taiwanese who was admitted to our hospital with refractory
      hypertension and refractory anemia following chronic hemodialysis for more than
      two years. He was diagnosed with Kimura's disease finally. Refractory
      hypertension and refractory anemia were noted over two years before an enlarged
      inguinal lymph node was observed. The symptoms lead to the diagnosis of Kimura's
      disease. Unlike most cases, refractory hypertension and refractory anemia were
      first noted before the inguinal mass and eosinophilia were presented. The
      inflammatory parameters increased when the disease was active. Steroid treatment
      was conducted, and the symptoms including hypertension and anemia promptly
      decreased. To the authors' knowledge, this case is for first one in which
      Kimura's disease has induced refractory hypertension and anemia in an ESRD
      patient and in which these symptoms rapidly subsided following steroid treatment.
      The activity of Kimura's disease is closely related refractory hypertension,
      suggesting that inflammation may be involved in refractory hypertension and
      anemia in a dialytic patient with Kimura's disease.

PMID- 12803516
TI  - Acute graft dysfunction due to pyelonephritis: value and safety of graft biopsy.

PMID- 12803517
TI  - Intermittent automatic veno-venous hemofiltration (IVVHF) and potassium removal:
      possible role in hyperkalemia.

PMID- 12803534
TI  - Biological motion as a cue for the perception of size.
AB  - Animals as well as humans adjust their gait patterns in order to minimize energy
      required for their locomotion. A particularly important factor is the constant
      force of earth's gravity. In many dynamic systems, gravity defines a relation
      between temporal and spatial parameters. The stride frequency of an animal that
      moves efficiently in terms of energy consumption depends on its size. In two
      psychophysical experiments, we investigated whether human observers can employ
      this relation in order to retrieve size information from point-light displays of
      dogs moving with varying stride frequencies across the screen. In Experiment 1,
      observers had to adjust the apparent size of a walking point-light dog by placing
      it at different depths in a three-dimensional depiction of a complex landscape.
      In Experiment 2, the size of the dog could be adjusted directly. Results show
      that displays with high stride frequencies are perceived to be smaller than
      displays with low stride frequencies and that this correlation perfectly reflects
      the predicted inverse quadratic relation between stride frequency and size. We
      conclude that biological motion can serve as a cue to retrieve the size of an
      animal and, therefore, to scale the visual environment.

PMID- 12803535
TI  - Neither here nor there: localizing conflicting visual attributes.
AB  - Natural visual scenes are a rich source of information. Objects often carry
      luminance, colour, motion, depth and textural cues, each of which can serve to
      aid detection and localization of the object within a scene. Contemporary
      neuroscience presumes a modular approach to visual analysis in which each of
      these attributes are processed within ostensibly independent visual streams and
      are transmitted to geographically distinct and functionally dedicated centres in
      visual cortex (van Essen & Maunsell, 1983; Zihl, von Cramon & Mai, 1983; Maunsell
      & Newsome, 1987; Tootell, Hadjikhani, Mendola, Marrett & Dale, 1998). In the
      present study we ask how the visual system localizes objects within this
      framework. Specifically, we investigate how the visual system assigns a unitary
      location to objects defined by multiple stimulus attributes, where such
      attributes provide conflicting positional cues. The results show that conflicting
      sources of visual information can be effortlessly combined to form a global
      estimate of spatial position, yet, this conflation of visual attributes is
      achieved at a cost to localization accuracy. Furthermore, our results suggest
      that the visual system assigns more perceptual weight (Landy, 1993; Landy &
      Kojima, 2001) to visual attributes which are reliably related to object contours.

PMID- 12803536
TI  - Distribution of the presynaptic calcium sensors, synaptotagmin I/II and
      synaptotagmin III, in the goldfish and rodent retinas.
AB  - Synaptic vesicle exocytosis is triggered by rises in calcium up to 100 microM at
      the site of vesicle fusion. The synaptic vesicle proteins synaptotagmin 1 and 2
      (Syt I and Syt II) bind calcium at similarly high concentrations and have been
      proposed as the calcium sensors for fast neurotransmitter release. However, 1
      microM calcium produces tonic transmitter release at photoreceptor and bipolar
      cell synapses in the goldfish retina, suggesting that these synapses use a higher
      affinity calcium sensor. Immunofluorescent staining with a panel of Syt I/II
      antibodies detected Syt I/II in both photoreceptor and bipolar cell terminals of
      the rodent retina. By contrast, no staining of either photoreceptor or protein
      kinase C (PKC)-labeled bipolar cell terminals was detected in the goldfish retina
      with any of the Syt I/II antibodies. The high affinity calcium sensor
      synaptotagmin 3 (Syt III) was localized to the synaptic layers of both goldfish
      and rodent retinas; however, while Syt III was associated with PKC-labeled
      bipolar cell terminals in the goldfish retina, it did not co-localize with PKC in
      the mouse retina. These results suggest that, unlike in their mammalian
      counterparts, synaptic vesicle exocytosis in goldfish photoreceptor and bipolar
      cell terminals utilizes a calcium sensor other than Syt I/II, possibly Syt III.

PMID- 12803537
TI  - Contour interpolation by vector-field combination.
AB  - We model the visual interpolation of missing contours by extending contour
      fragments under a smoothness constraint. Interpolated trajectories result from an
      algorithm that computes the vector sum of two fields corresponding to different
      unification factors: the good continuation (GC) field and the minimal path (MP)
      field. As the distance from terminators increases, the GC field decreases and the
      MP field increases. Viewer-independent and viewer-dependent variables modulate GC
      MP contrast (i.e., the relative strength of GC and MP maximum vector magnitudes).
      Viewer-independent variables include the local geometry as well as more global
      properties such as contour support ratio and shape regularity. Viewer-dependent
      variables include the retinal gap between contour endpoints and the retinal
      orientation of their stems. GC-MP contrast is the only free parameter of our
      field model. In the case of partially occluded angles, interpolated trajectories
      become flatter as GC-MP contrast decreases. Once GC-MP contrast is set to a
      specific value, derived from empirical measures on a given configuration, the
      model predicts all interpolation trajectories corresponding to different types of
      occlusion of the same angle. Model predictions fit psychophysical data on the
      effects of viewer-independent and viewer-dependent variables.

PMID- 12803538
TI  - Spatiotemporal relationships in a dynamic scene: stereomotion induction and
      suppression.
AB  - We establish the existence of purely stereoscopic motion induction, i.e.,
      perceived depth motion induced into a fixed-disparity target by disparity changes
      in a surround region. The stimuli were dynamic autostereograms consisting of a
      target and a surround, both consisting of horizontal lines of discs. We explored
      the stereomotion induction process by (i) direct estimation of the perceived
      distance moved, (ii) a cancellation technique with compensatory target motion,
      and (iii) extension of the compensatory motion into the zone beyond the null
      point. Adding compensatory stereomotion to the target reduced the induced motion
      experience to a null point. Beyond the cancellation point, two surprising results
      were obtained; perceived motion in the target increased, while the surround
      stereomotion perception was almost suppressed over a wide range of disparity
      changes (reciprocal stereomotion suppression). A model of the target/surround
      interactions was developed in the context of dynamic organization principles
      operating in stereomotion perception and misperception.

PMID- 12803539
TI  - Prediction of size distribution of lipid-peptide-DNA vector particles using Monte
      Carlo simulation techniques.
AB  - Concerns with insertional mutagenesis for retrovirus and immunogenicity for
      adenovirus have motivated research into development of non-viral vectors that can
      safely deliver desired gene constructs to target cells in tissues and organs.
      Many non-viral vectors suffer from unacceptably poor in vivo cell transfection
      and low transgene expression. Evidence suggests that cell transfection is linked
      to particle size - vector particles below about 200 nm are considered desirable.
      Experimental measurements indicate, however, that vector particles are
      susceptible to significant aggregation under most conditions of pH and ionic
      strength, including physiological conditions, although there are currently no
      means of predicting the kinetics of aggregation. The present paper addresses this
      challenge by presenting a mathematical framework based on the Monte Carlo
      simulation techniques for modelling the dynamics of aggregation. The approach is
      used to simulate the evolution of particle-size distribution for an integrin
      targeting lipid-peptide-DNA vector system in buffers of different pH and ionic
      strength. The simulations required two input parameters, including the initial
      size distribution of the particles and a fitting parameter (alpha). Comparison of
      simulations with experimental data showed that alpha was closely related to the
      zeta potential of the particles in the buffer medium, making simulations fully
      predictive. The modelling approach may be used in other vector systems.

PMID- 12803540
TI  - Genomic identification and biochemical characterization of a second
      spermidine/spermine N1-acetyltransferase.
AB  - In the polyamine back-conversion pathway, spermine and spermidine are first
      acetylated by spermidine/spermine N(1) -acetyl-transferase (SSAT-1) and then
      oxidized by polyamine oxidase to produce spermidine and putrescine respectively.
      Herein we apply homology-search methods to identify novel sequences belonging to
      a second SSAT, SSAT-2, with a chromosomal location at 17p13.1, which is distinct
      from SSAT-1 at Xp22. Human SSAT-2 cDNA derived from small-cell lung carcinoma was
      deduced to encode a 170-amino-acid protein having 46% sequence identity and 64%
      sequence similarity with SSAT-1. When transiently transfected into HEK-293 cells,
      SSAT-1 decreased spermidine and spermine pools by approximately 30%, while, at
      the same time, significantly increasing putrescine, N (1)-acetylspermidine, N (1)
      acetylspermine and N (1), N (12)-diacetylspermine pools. By contrast, transfected
      SSAT-2 had no effect on intracellular polyamine or acetylated polyamine pools.
      When enzyme activity was assayed on enzyme extracts from transfected cells, both
      SSAT-1 and SSAT-2 demonstrated much higher acetylating activity than vector
      transfected cells. The data suggest that, in intact cells, SSAT-2 may be
      compartmentalized or it may be inefficient at low intracellular polyamine
      concentrations. By substituting candidate substrates in the enzyme assay, we
      determined that SSAT-1 shows the substrate preference
      norspermidine=spermidine>>spermine> N (1)-acetylspermine>putrescine, whereas SSAT
      2 shows the preference norspermidine>spermidine=spermine>> N (1)
      acetylspermine=putrescine. Analysis of mRNA levels in cell lines and ESTs
      (expressed sequence tags) from various tissues by digiNorthern (a web-based tool
      for virtually displaying expression profiles of query genes based on EST
      sequences) indicated that SSAT-1 tends to be more widely and highly expressed
      than SSAT-2. While SSAT-1 mRNA was inducible by polyamine analogues in a variety
      of cell lines, SSAT-2 was not. The existence of an active, but possibly
      sequestered, SSAT-2 enzyme suggests that, under certain conditions, it may be
      recruited into basal or perturbed polyamine metabolism.

PMID- 12803541
TI  - Gamma III-crystallin is the primary target of glycation in the bovine lens
      incubated under physiological conditions.
AB  - Several mechanisms have been proposed for the way in which glucose and its
      metabolites cause cataract, retinopathy and other complications of diabetes, the
      most convincing being glycation. Glycation, the reaction of sugars with free
      amino groups of proteins, is one of a variety of non-enzymic post-translational
      modifications. The aim of the present study was to identify some of the most
      reactive proteins in the lens when incubated under physiological conditions.
      Fresh intact bovine lenses were incubated with [14C]glucose in a conventional
      tissue-culture medium with added antibiotics. After 3 and 6 days of incubation,
      the water-soluble proteins were separated by size-exclusion chromatography.
      Glycated proteins from the water-soluble fractions were separated by using a
      sugar affinity column (Affi-Gel 601). Then the radioactive fractions were
      identified on SDS/polyacrylamide gels. In addition, the whole bovine lenses were
      incubated with 10 mM fructose and glucose for 3 and 6 days. The glycated proteins
      from the water-soluble fractions in parallel with the radioactive fractions were
      separated by affinity chromatography, and were identified further by amino-acid
      sequencing. A progressive uptake of radioactive label showed that the majority of
      proteins incorporating both glucose and fructose were water-soluble fractions.
      Chromatography and SDS/polyacrylamide gel results showed that alpha- and gamma
      crystallin and some proteins of a mean molecular mass of 36-37 kDa incorporated
      sugars early during incubation. After 6 days of incubation, more crystallins were
      glycated compared with 3 days, in particular beta-crystallin. Affinity
      chromatography results indicated that proteins with subunit masses of 36 kDa and
      20 kDa were possibly radiolabelled at an early stage. The purified glycated
      proteins following incubation with both glucose and fructose, which corresponded
      to 20 kDa and 36 kDa bands on SDS/polyacrylamide gels, were sequenced by Edman
      degradation. N-terminal sequences of both 20 kDa bands were Gly-Lys-Ile-Thr,
      characteristic of gamma-crystallins, but the N-termini of both 36 kDa bands were
      blocked. Further sequencing after digestion of 36 kDa bands with trypsin and
      running on HPLC revealed that the glucose sample gave the peptide sequences as
      Gly-Glu-Tyr-Pro-Asp-Tyr-Gln-Gln and Tyr-Glu-Leu-Pro-Asn-Tyr-Arg, which match with
      bovine gammaIIIb-crystallin. The peptide sequence Tyr-Glu-Leu-Pro-Asn-Tyr-Arg is
      only present in the published sequence of bovine gammaIIIb-crystallin and not in
      any other type of gamma-crystallin. The fructose sample gave the peptide
      sequences Ile-Thr-Phe-Tyr-Glu-Asp-Arg, Arg-Gly-Asp-Tyr-Pro-Asp-Tyr-Gln-Gln-Trp,
      Gln-Tyr-Leu-Leu-Arg and Val-Val-Asp-Leu-Tyr, which all matched with bovine
      gammaIIIa-crystallin. The sequence Val-Val-Asp-Leu-Tyr only appears in the
      sequence of bovine gammaIIIa-crystallin. gammaIII-Crystallin is the most
      susceptible lens protein to glycation. The primary target of glucose is gammaIIIb
      crystallin, whereas that of fructose is gammaIIIa-crystallin. The early glycation
      of gammaIII-crystallin by glucose and fructose could result in structural
      alterations, leading to aggregation of crystallin and eventually cataract
      formation.

PMID- 12803542
TI  - The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced
      and processed by a furin-like proprotein convertase.
AB  - Epilysin (MMP-28) is a recently identified member of the matrix metalloproteinase
      (MMP) family. To explore the expression of epilysin in vivo and to gain insight
      into its biological functions, we have cloned the mouse epilysin cDNA and
      determined its expression. The amino acid sequence of the mouse protein is 85%
      identical with the human sequence and contains conserved features such as an RKKR
      furin-activation sequence following the prodomain. Unexpectedly, we found two
      alternatively spliced forms of the epilysin mRNA lacking 30 and 72 nt at the
      beginning of the seventh exon coding for part of the haemopexin domain.
      Expression of recombinant epilysin in HT-1080 fibrosarcoma cells indicated that
      epilysin was secreted as a major 48 kDa form and a minor 58 kDa form. Expression
      of the 58 kDa form was increased by a synthetic furin inhibitor at the expense of
      the 48 kDa form, suggesting that furin cleaves and activates epilysin. Epilysin
      mRNA was detected in a number of mouse tissues, with the highest expression in
      the lung, placenta, heart and uterus, and lower levels in the testis and
      gastrointestinal tract. The wide expression of epilysin in intact, healthy
      tissues suggests that this MMP functions in physiological tissue homoeostasis and
      turnover.

PMID- 12803545
TI  - Sphingosine-1-phosphate receptor subtype-specific positive and negative
      regulation of Rac and haematogenous metastasis of melanoma cells.
AB  - We have recently reported that S1P (sphingosine-1-phosphate) differentially
      regulates cellular Rac activity and cell migration in either a positive or a
      negative direction via distinct G-protein-coupled receptor subtypes, i.e.
      S1P1/Edg1 (endothelial differentiation gene) and S1P2/Edg5 respectively, when
      each of the S1P receptor subtypes is expressed in CHO (Chinese-hamster ovary)
      cells. In B16F10 mouse melanoma cells, in which S1P2, but not the other S1P
      receptor subtypes, is endogenously expressed, S1P inhibited cell migration with
      concomitant inhibition of Rac and stimulation of RhoA in dose-dependent manners.
      Overexpression of S1P2 in the melanoma cells resulted in potentiation of S1P
      inhibition of both Rac and cell migration. In contrast, overexpression of S1P1
      led to stimulation of cell migration, particularly at the lower S1P
      concentrations. Treatment of B16F10 cells with S1P inhibited lung metastasis 3
      weeks after injection into mouse tail veins. Intriguingly, overexpression of S1P2
      greatly potentiated the inhibition of metastasis by S1P, whereas that of S1P1
      resulted in aggravation of metastasis. Suppression of cellular Rac activity by
      adenovirus-transduced expression of N17Rac, but not N19RhoA, strongly inhibited
      cell migration in vitro and lung metastasis in vivo. These results provide the
      first evidence that G-protein-coupled receptors could participate in the
      regulation of metastasis, in which ligand-dependent, subtype-specific regulation
      of the cellular Rac activity is probably critically involved as a mechanism.

PMID- 12803544
TI  - Oxidation of thioanisole and p-methoxythioanisole by lignin peroxidase: kinetic
      evidence of a direct reaction between compound II and a radical cation.
AB  - The reaction of H2O2 with thioanisole and p-methoxythioanisole catalysed by
      lignin peroxidase from Phanerochaete chrysosporium has been studied
      spectrophotometrically under turnover and single turnover conditions with a
      stopped-flow apparatus. Pre-formed lignin peroxidase compounds I and II are each
      able to react with the sulphides to form a sulphide radical cation. The radical
      cation is then converted into the sulphoxide either by reaction with the medium
      or by reaction with compound II. This is the first report of a direct reaction
      between compound II and the substrate radical cation. With thioanisole,
      significant enantiomeric selectivity and high oxygen incorporation in the
      sulphoxide are obtained because compound II is preferentially reduced by the
      enzyme-bound thioanisole radical cation compared with the neutral substrate. By
      contrast, with p-methoxythioanisole, the data imply formation of an intermediate
      ternary complex comprising compound II, radical cation and neutral substrate,
      such that a chain of electron transfer reactions starting from neutral molecule
      and progressing to oxidized haem via substrate radical cation is facilitated,
      yielding the native enzyme and two molecules of p-methoxythioanisole radical
      cation as products. The reactions of compounds I and II with sulphides imply
      flexing of the apoprotein moiety during catalysis.

PMID- 12803547
TI  - Degradation of the main components of cellulose-paint thinner by the mould
      Scopulariopsis brevicaulis cultured on rice hulls.
AB  - AIMS: Biodegradation of the main components of the cellulose-paint thinner
      (toluene, acetone, isopropanol and xylenes) by Scopulariopsis brevicaulis,
      isolated from a thinner biodegradation microbial consortium was investigated.
      METHODS AND RESULTS: Our results showed that 90% of S. brevicaulis conidia
      survived after 4 weeks in a cellulose-paint thinner saturated atmosphere. The
      mould was able to grow under these environmental conditions with a low
      development of conidia. The biodegradation potential of S. brevicaulis was
      established with and without support material (rice hulls). Biodegradation
      without support was very limited, <10% for all the components quantified. There
      was notable thinner biodegradation when the fungus was grown on rice hulls.
      CONCLUSIONS: Our results suggest the potential use of fungi in biofiltration
      systems employed in biodegradation of the main components of the cellulose-paint
      thinner. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of
      volatile organic compounds biodegradation by this fungal species.

PMID- 12803548
TI  - Identification of heterofermentative lactobacilli isolated from pig faeces by
      numerical analysis of total soluble cell protein patterns and RAPD-PCR.
AB  - AIMS: The study deals with a number of heterofermentative Lactobacillus strains
      isolated from pig faeces and their identification. METHODS AND RESULTS: SDS-PAGE
      of total soluble cell proteins and RAPD-PCR profiles were used to identify the
      strains isolated from pig faeces. Protein profiles obtained with SDS-PAGE
      revealed that 15 strains clustered at r >or= 0.78 with Lactobacillus buchneri and
      nine strains at r >or= 0.77 with two reference strains of Lactobacillus reuteri.
      The identity of the strains was confirmed with RAPD-PCR. CONCLUSIONS: Numerical
      analysis of protein profiles and RAPD-PCR proved valuable in the differentiation
      of Lactobacillus spp. isolated from pig faeces. SIGNIFICANCE: This is the first
      report on the association of Lact. buchneri with pig faeces.

PMID- 12803546
TI  - Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and
      amlexanox.
AB  - Hsp90 (heat-shock protein 90) alone can act to prevent protein aggregation and
      promote refolding in vitro, but in vivo it operates as a part of a multichaperone
      complex, which includes Hsp70 and cohort proteins. Since the physiological
      function of Hsp90 is not yet fully understood, the development of specific
      antagonists might open new lines of investigation on the role of Hsp90. In an
      effort to discover Hsp90 antagonists, we screened many drugs and found that the
      anti-allergic drugs DSCG (disodium cromoglycate) and amlexanox target Hsp90. Both
      drugs were found to bind directly wild-type Hsp90 via the N- and C-terminal
      domains. Both drugs strongly suppressed the in vitro chaperone activity of native
      Hsp90 towards citrate synthase at 1.5-3.0 microM. Amlexanox suppressed C-terminal
      chaperone activity in vitro, but not N-terminal chaperone activity, and inhibited
      the association of cohort proteins, such as cyclophilin 40 and Hsp-organizing
      protein, to the C-terminal domain of Hsp90. These data suggest that amlexanox
      might disrupt the multichaperone complex, including Hsp70 and cohort proteins,
      both in vitro and in vivo. Although DSCG inhibited the in vitro chaperone
      activity of the N-terminal domain, the drug had no effect either on the C
      terminal chaperone activity or on the association of the cohort proteins with the
      C-terminus of Hsp90. The physiological significance of these interactions in vivo
      remains to be investigated further, but undoubtedly must be taken into account
      when considering the pharmacology of anti-allergic drugs. DSCG and amlexanox may
      serve as useful tools for evaluating the physiological significance of Hsp90.

PMID- 12803549
TI  - Destruction of Bacillus anthracis strain Sterne 34F2 spores in postal envelopes
      by exposure to electron beam irradiation.
AB  - AIMS: To determine the irradiation dose necessary to reduce the populations of
      Bacillus anthracis spores in a dry medium in postal envelopes. METHODS AND
      RESULTS: Bacillus anthracis Sterne 34F2 spores were dispersed in non-fat dry milk
      and then placed into standard business postal envelopes. The spores were treated
      with a sequence of irradiation doses to determine the decimal reduction value
      (D10) in kiloGrays (kGy). The average D10 value was 3.35 +/- 0.02 kGy.
      CONCLUSIONS: An irradiation dose of 40.2 kGy would be required to result in a
      process equivalent to the thermal canning process (12 D10 reduction) to eliminate
      Clostridium botulinum spores. SIGNIFICANCE AND IMPACT OF THE STUDY: Irradiation
      is an effective means of reducing or eliminating B. anthracis spores in a dry
      medium in postal envelopes.

PMID- 12803550
TI  - Overlapping role of the outer membrane cytochromes of Shewanella oneidensis MR-1
      in the reduction of manganese(IV) oxide.
AB  - AIM: To determine if the outer membrane (OM) cytochromes OmcA and OmcB of the
      metal-reducing bacterium Shewanella oneidensis MR-1 have distinct or overlapping
      roles in the reduction of insoluble manganese(IV) oxide. METHODS AND RESULTS: The
      gene replacement mutant (OMCA1) which lacks OmcA was partially deficient in
      Mn(IV) reduction. Complementation of OMCA1 with a vector (pVK21) that contains
      omcB but not omcA restored Mn(IV) reduction to levels that were even greater than
      those of wild-type. Examination of the OM of OMCA1/pVK21 revealed greater than
      wild-type levels of OmcB protein and specific haem content. CONCLUSIONS:
      Overexpression of OmcB can compensate for the absence of OmcA in the reduction of
      insoluble Mn(IV) oxides. Therefore, there is at least a partial overlap in the
      roles of these OM cytochromes in the reduction of insoluble Mn(IV) oxide.
      SIGNIFICANCE: The overlapping roles of these two cytochromes has important
      implications for understanding the mechanism by which MR-1 reduces insoluble
      metal oxides. There is no obligatory sequential electron transfer from one
      cytochrome to the other. They could both potentially serve as terminal reductases
      for extracellular electron acceptors.

PMID- 12803551
TI  - Modelling the individual cell lag phase. Isolating single cells: protocol
      development.
AB  - AIMS: To develop a protocol to isolate single cells in wells of a microtitre
      plate, having a high certainty of individual cells, combined with a sufficient
      yield. METHODS AND RESULTS: Single cells were obtained using 1/2 dilution series
      in microtitre plates. Seventy-two Lactococcus lactis dilution series were checked
      by plate counting. When the last five columns of the plates were observed, the
      chance of having one single cell was 80%, while the yield was 75 wells containing
      cells. A simulation model confirmed these results. This method was compared with
      the commonly applied method. CONCLUSIONS: This method makes it possible to
      combine a higher chance of having one cell in a microtitre well with a slightly
      higher yield. SIGNIFICANCE AND IMPACT OF THE STUDY: A tool is developed to
      isolate single cells to provide a suitable base for investigating and modelling
      the individual cell lag phase.

PMID- 12803552
TI  - Effect of feed gas composition of gas discharge plasmas on Bacillus pumilus spore
      mortality.
AB  - AIMS: To investigate the effect of gas composition on the sensitivity of Bacillus
      pumilus spores to gas plasmas. METHODS AND RESULTS: Inert gas plasmas, oxygen
      based plasmas and various moisturized air plasmas were used to inactivate B.
      pumilus spores in low gas pressure of 50 Pa. Although the treatment temperature
      did not exceed 55 degrees C when exciting these plasmas, spore survival varied
      widely depending on the composition of the gas feed. Higher spore mortality was
      acquired by inert gases of low molecular weight except for helium. The highest
      spore mortality (4.54log reduction) was obtained when air with a 0.05 molar
      fraction of water vapour was used as the plasma carrier gas. CONCLUSIONS: Water
      molecules in the plasma carrier gas play a significant role in inactivation of B.
      pumilus spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This strong inactivation
      may occur through hydroxyl free radicals generated from the moisturized air
      plasma.

PMID- 12803553
TI  - Effects of mixtures of lauric and myristic acid on rumen methanogens and
      methanogenesis in vitro.
AB  - AIMS: To identify the most effective mixture of non-esterified lauric (C12) and
      myristic (C14) acid in suppressing ruminal methanogenesis, and to investigate
      their effects on the methanogenic population. METHODS AND RESULTS: C12/C14
      mixtures were incubated with rumen fluid using the Hohenheim gas test apparatus.
      Methane production and the numbers of Archaea declined with an increasing
      proportion of C12. With a 2 : 1 proportion of C12/C14, the maximum methane
      suppressing effect (96%) was achieved similar to that with C12 alone. The
      proportions of the individual methanogenic orders of total methanogens were
      altered by varying the C12/C14 ratio. CONCLUSIONS: Although C14 alone had no
      effect on methanogenesis, C14 enhanced the methane-suppressing effect of C12 in
      certain mixtures. SIGNIFICANCE AND IMPACT OF THE STUDY: The results support
      strategies for an environment-friendly ruminant nutrition as it was demonstrated
      that part of the less palatable C12 could be replaced by C14 without losing its
      methane-suppressing potential.

PMID- 12803554
TI  - Measurement of fungi by an indirect conductimetric assay.
AB  - AIMS: To investigate the growth of fungi using an indirect conductimetric assay
      and derive, experimentally and theoretically, the relationship between microbial
      concentration and electrical conductivity change. METHODS AND RESULTS: The
      indirect assay, in which change in electrical conductivity of an alkaline
      solution (NaOH) is produced by absorption of CO2 from microbial metabolism, was
      conducted with the Bactometer (bioMerieux, Marcy-l'Etoile, France) for the
      enumeration of fungi. A linear relationship was obtained between detection time
      and logarithmic initial microbial concentration. This indirect assay used growth
      media, which could not be used in the direct conductimetric assay, to monitor
      fungal growth. CONCLUSIONS: The indirect assay does not depend on the growth
      media and the turbidity of sample and could offer a simple and rapid assay for
      the measurement of fungal growth under various conditions. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The indirect assay is applicable for rapid detection of
      fungi, estimation of the growth rate and evaluation of antifungal activity.

PMID- 12803543
TI  - RecQ helicases: suppressors of tumorigenesis and premature aging.
AB  - The RecQ helicases represent a subfamily of DNA helicases that are highly
      conserved in evolution. Loss of RecQ helicase function leads to a breakdown in
      the maintenance of genome integrity, in particular hyper-recombination. Germ-line
      defects in three of the five known human RecQ helicases give rise to defined
      genetic disorders associated with cancer predisposition and/or premature aging.
      These are Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome,
      which are caused by defects in the genes BLM, WRN and RECQ4 respectively. Here we
      review the properties of RecQ helicases in organisms from bacteria to humans,
      with an emphasis on the biochemical functions of these enzymes and the range of
      protein partners that they operate with. We will discuss models in which RecQ
      helicases are required to protect against replication fork demise, either through
      prevention of fork breakdown or restoration of productive DNA synthesis.

PMID- 12803555
TI  - Survivability and long-term preservation of bacteria in water and in phosphate
      buffered saline.
AB  - AIMS: To evaluate the suitability of using sterile water and phosphate-buffered
      saline (PBS) for preservation of bacteria pathogenic to plants or humans. METHODS
      AND RESULTS: The stationary-phase bacterial cells collected from rich agar media
      were transferred to 10 ml of sterile water or PBS (pH 7.2) containing KH2PO4,
      15.44 microm; NaCl, 1.55 mm; Na2HPO4, 27.09 microm in a screw-cap tube. The tubes
      were sealed with parafilm membranes and stored in the dark and at room
      temperature. Almost all the bacteria tested (148 strains), including Pseudomonas
      fluorescens, P. viridiflava, Erwinia spp., Xanthomonas campestris, Cytophaga
      johnsonae, Salmonella spp., Yersinia enterocolitica, Escherichia coli O157:H7,
      Listeria monocytogenes and Staphylococcus aureus, survived in water for at least
      several months and up to 16 years. A vast majority of the Gram-negative bacteria
      tested survived equally well in water and in PBS for at least 30 weeks. However,
      the populations of two Gram-positive bacteria [G(+)], L. monocytogenes and Staph.
      aureus, declined more rapidly in water than in PBS. CONCLUSIONS: Plant- and human
      pathogenic bacteria can be preserved in pure water or PBS for several years. G(+)
      bacteria appear to survive better in PBS than in water. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The method described here is a simple and economical means for
      preservation of bacterial cultures, which is especially useful for laboratories
      not equipped with the lyophilizer or ultra-low freezer. Long-term survival of
      food-borne pathogens in water underlines the importance of water as a potential
      vehicle for transmitting the diseases.

PMID- 12803556
TI  - Influence of pH drop on both nisin and pediocin production by Lactococcus lactis
      and Pediococcus acidilactici.
AB  - AIMS: To develop a kinetic model for describing the specific effect of pH drop on
      nisin and pediocin production in whey. METHODS AND RESULTS: The effect of pH drop
      on both bacteriocin productions was tested in non-buffered whey and whey buffered
      at initial pH 6.3 with 0.03, 0.10 and 0.25 mol l-1 of potassium hydrogen
      phthalate-NaOH. An accurate description of the experimental data of nisin and
      pediocin obtained at different pH drops is obtained with the proposed model.
      CONCLUSIONS: The proposed model was able to typify both bacteriocins as pH
      dependent primary metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: The decisive
      role of pH drop for bacteriocin production on whey was demonstrated and modelled.
      This study contributes to a better understanding of underlying metabolic
      regulatory mechanisms, which could facilitate the optimization of bacteriocin
      production for upscaling.

PMID- 12803557
TI  - PCR detection of Actinobacillus pleuropneumoniaeapxIV gene in formalin-fixed,
      paraffin-embedded lung tissues and comparison with in situ hybridization.
AB  - AIMS: Formalin-fixed, paraffin-embedded lung tissues from pigs experimentally
      infected with 12 Actinobacillus pleuropneumoniae serotypes were used to develop
      nested PCR for the detection of apxIV gene. METHODS AND RESULTS: The PCR results
      from formalin-fixed, paraffin-embedded tissues were compared with in situ
      hybridization. The apxIV gene was detected in formalin-fixed, paraffin-embedded
      lung tissues from all 39 pigs experimentally infected with 12 A. pleuropneumoniae
      serotypes by nested PCR. In situ hybridization produced a distinct positive
      signal in all 39 pigs experimentally infected with 12 A. pleuropneumoniae
      serotypes. Agreement rates between nested PCR and in situ hybridization were 100%
      for the detection of apxIV gene in formalin-fixed paraffin-embedded lung tissues.
      Acceptable PCR signals were detected from lung tissues fixed for periods up to
      180 days. CONCLUSIONS: The apxIV gene is species-specific rather than serotype
      specific and is therefore an important diagnostic marker. The nested PCR assay
      would be a useful method for the detection of apxIV gene to diagnose A.
      pleuropneumoniae infection when formalin-fixed tissues are submitted.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirmed the possibility of
      using formalin-fixed, paraffin-embedded tissues for the diagnosis of A.
      pleuropneumoniae infection in pigs.

PMID- 12803558
TI  - Bacteriocidal effects and inhibition of cell separation of cinnamic aldehyde on
      Bacillus cereus.
AB  - AIMS: In this study, bacteriocidal effects of cinnamic aldehyde on Bacillus
      cereus were investigated. METHODS: The bacterial culture or cell suspension in
      0.85% NaCl was treated with cinnamic aldehyde at a concentration of 0.3 ml l(-1).
      Viable cells were counted on a nutrient agar plate. Protein leakage from the cell
      was determined using a protein dye. Cell morphology was observed using a scanning
      electron microscope. RESULTS: Bacillus cereus cells were the most sensitive to
      cinnamic aldehyde among four different food-borne pathogens. When the cells were
      treated with 0.3 ml l(-1) of cinnamic aldehyde, the viable counts decreased about
      6 log cycles after 6 h of incubation. The bacterial cells remained unlysed
      although they were killed by cinnamic aldehyde. Treatment of cinnamic aldehyde to
      the exponential phase cells resulted in no significant protein leakage but strong
      inhibition of cell separation. CONCLUSIONS: The present findings suggest that
      cinnamic aldehyde exhibits bacteriocidal effects and inhibition of cell
      separation on B. cereus. SIGNIFICANCE AND IMPACT OF THE STUDY: These data
      represent an interesting background for a possible mechanism for antibacterial
      effects of cinnamic aldehyde.

PMID- 12803559
TI  - Nested PCR for detection of mutans streptococci in dental plaque.
AB  - AIMS: Mutans streptococci such as Streptococcus mutans and Streptococcus sobrinus
      have been implicated in human dental caries. In an attempt to develop a rapid and
      sensitive method for detecting Strep. mutans and Strep. sobrinus in dental
      plaque, a nested PCR amplification based on the 16S rRNA gene was employed.
      METHODS AND RESULTS: A universal set of PCR primers for bacterial 16S rRNA gene
      was introduced for the first PCR, and then two sets of primers specific for the
      16S rRNA gene sequences of either Strep. mutans or Strep. sobrinus were used for
      the second PCR. Eighteen plaque samples were analyzed, and a nested PCR was shown
      to be more sensitive for detecting Strep. mutans and Strep. sobrinus than direct
      PCR. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The 16S rRNA gene-based
      nested PCR method is a rapid and sensitive method for the detection of mutans
      streptococci, and may also be suitable for carrying out large-scale studies on
      the cariogenicity of mutans streptococci.

PMID- 12803560
TI  - Two-dimensional environmental profiles of growth, deoxynivalenol and nivalenol
      production by Fusarium culmorum on a wheat-based substrate.
AB  - AIMS: To determine the effect of interacting conditions of water activity (aw,
      0.99-0.85), temperature (15, 25 degrees C) and time (40 days) on growth and
      production of the mycotoxins deoxynivalenol (DON) and nivalenol (NIV) by Fusarium
      culmorum on a wheat-based agar medium. METHODS AND RESULTS: Fusarium culmorum
      grew optimally at 0.995aw and minimally at 0.90 at both 15 and 25 degrees C. No
      growth was observed at <0.90aw. Overall, temperature, aw and their interaction
      had a statistically significant effect on the growth rate of F. culmorum.
      Production of both DON and NIV were over a much narrower range (0.995-0.95aw)
      than that for growth. The highest concentrations of DON and NIV levels were
      produced at 0.995aw and 0.981aw at 25 degrees C, respectively, after 40 days of
      incubation. Statistically, aw, temperature and incubation time, and aw x
      temperature and temperature x incubation time had a statistically significant
      effect on DON/NIV production. CONCLUSIONS: This is the first detailed report on
      the two-dimensional environmental profiles for DON/NIV production by F. culmorum
      in the UK. SIGNIFICANCE AND IMPACT OF THE STUDY: As part of a hazard analysis
      critical control point (HACCP) approach, this type of information is critical in
      monitoring critical control points for prevention of DON/NIV entering the wheat
      production chain.

PMID- 12803561
TI  - Enhanced secretion of heterologous cyclodextrin glycosyltransferase by a mutant
      of Bacillus licheniformis defective in the D-alanylation of teichoic acids.
AB  - AIMS: To examine whether inactivation of the dlt operon and increased charge
      density of the wall enhances secretion of heterologous proteins in industrial
      strains of Bacillus licheniformis. METHODS AND RESULTS: The dltA gene of B.
      licheniformis was cloned, sequenced and mutated by inserting a chloramphenicol
      acetyl transferase (cat) gene cassette. The mutation facilitated growth in the
      late exponential growth phase, increased endogenous autolysis and decreased
      resistance to a cationic peptide, polylysine. It was observed that dltA mutation
      increased the production of cyclodextrin glycosyltransferase (CGTase) by 1.5- to
      sevenfold depending on the growth phase, but decreased the production of
      penicillinase by twofold. CONCLUSIONS AND SIGNIFICANCE: The results suggest that
      the d-alanylation of teichoic acids is an element that can be used to improve the
      production of some secretory proteins in industrial applications based on this
      important industrial microorganism.

PMID- 12803562
TI  - Erythrina poeppigiana-derived phytochemical exhibiting antimicrobial activity
      against Candida albicans and methicillin-resistant Staphylococcus aureus.
AB  - AIMS: To screen five phytochemicals isolated from Erythrina poeppigiana
      (Leguminosae) for antimicrobial activity against both Candida albicans and
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: Roots of
      E. poeppigiana were macerated with acetone and the chloroform-soluble fraction of
      the residue was subjected to repeated silica gel column chromatography using
      various eluting solvents. Structures of the isolated compounds were determined by
      extensive spectroscopic studies. Each compound was dissolved in dimethyl
      sulphoxide and added to agar plates (final concentration: 1.56-100 microg ml(-1))
      and minimum inhibitory concentrations (MICs) against C. albicans and MRSA were
      determined. Spectral data indicated the presence of three different types of
      phytochemicals; isoflavonoids (erypoegin A, demethylmedicarpin and sandwicensin),
      alpha-methyldeoxybenzoin (angolensin) and cinnamylphenol (erypostyrene). While
      all compounds showed anti-MRSA activity in this concentration range,
      isoflavonoids and alpha-methyldeoxybenzoin failed to inhibit the growth of C.
      albicans. Erypostyrene (E-1-[2-hydroxy-4-methoxy-5-(gamma,gamma
      dimethylallyl)benzyl]-2-(4-hydroxyphenyl)ethylene) exhibited not only the highest
      anti-MRSA activity (MIC value of 6.25 microg ml(-1)) but also anti-candidal
      potency (MIC value of 50 microg ml(-1)). The compound reduced viable cell numbers
      of C. albicans and MRSA by approximately 1 of 2000 and 1 of 1000 after 1 h
      incubation at each MIC, respectively. CONCLUSIONS: A new cinnamylphenol,
      erypostyrene, possessed anti-candidal and anti-MRSA activity. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Erypostyrene could be a leading candidate for development of
      antimicrobial agents with anti-candidal and anti-MRSA activity.

PMID- 12803563
TI  - Fungicidal and anti-aflatoxigenic effects of the essential oil of Cymbopogon
      citratus (DC.) Stapf. (lemongrass) against Aspergillus flavus Link. isolated from
      stored rice.
AB  - AIMS: To develop a natural fungicide against aflatoxigenic fungi, to protect
      stored rice, using the essential oil of lemongrass. METHODS AND RESULTS:
      Aspergillus flavus Link. was isolated from stored rice and identified as an
      aflatoxigenic strain. Lemongrass oil was tested against A. flavus and the test
      oil was fungistatic and fungicidal against the test pathogen at 0.6 and 1.0 mg
      ml(-1), respectively. Aflatoxin production was completely inhibited at 0.1 mg ml(
      1). The results obtained from the thin layer chromatographic bioassay and gas
      chromatography indicated citral a and b as the fungicidal constituents in
      lemongrass oil. During the fumigant toxicity assay of lemongrass oil, the
      sporulation and the mycelial growth of the test pathogen were inhibited at the
      concentrations of 2.80 and 3.46 mg ml(-1), respectively. CONCLUSION: Lemongrass
      oil could be used to manage aflatoxin formation and fungal growth of A. flavus in
      stored rice. SIGNIFICANCE AND IMPACT OF THE STUDY: Currently, fungicides are not
      used to control fungal pests or mycotoxin production on stored rice. Rice treated
      with the essential oil of lemongrass could be used to manage fungal pests as well
      as the insect pests in stored rice. The essential oil is chemically safe and
      acceptable to consumers, as synthetic chemical fungicides can cause adverse
      health effects to consumers.

PMID- 12803567
TI  - Self-medication: from European regulatory directives to therapeutic strategy.
AB  - Self medications are drugs which can be used without a physician's advice or
      supervision. There is a clear emerging patient demand for efficient drugs
      available without prescription. This review summarizes the regulatory rules
      regarding the status of self-medication drugs in Europe and describes some
      situations where specific clinical trials are needed for a new drug to be
      registered as a self medication. These drugs not only have to offer a very
      positive safety profile but also a well-established level of efficacy. A
      nonprescription drug can only be proposed in situations where the patient himself
      can make a self-assessment of the medical condition and its follow-up. These
      products must be safe even in the event of incorrect use and must offer clear and
      complete information contributing to a proper use, i.e. a definition of
      situations where a physician's advice is necessary. For registration as an 'over
      the-counter' drug, specific efficacy trials may be conducted in real self
      medication situation especially when the target populations, the dosage or the
      indications in self medication are not the same as those evaluated previously
      when the drug in question had prescription status. Specific pharmacovigilance is
      needed and the patient, pharmacist and physician encouraged to report any adverse
      events. A safety survey may be necessary in some situations such as insomnia or
      emergency contraception. It is important for the patient, pharmacist and public
      health in general to distinguish the efficient and safe self medications from the
      nonvalidated, nonevaluated alternative medicines.

PMID- 12803568
TI  - Drug metabolism and disposition in children.
AB  - Key factors undergoing maturational changes accounting for differences in drug
      metabolism and disposition in the pediatric population compared with adults are
      reviewed. Gastric and duodenal pH, gastric emptying time, intestinal transit
      time, bacterial colonization and probably P-glycoprotein are important factors
      for drug absorption, whereas key factors explaining differences in drug
      distribution between the pediatric population and adults are membrane
      permeability, plasma protein concentration and plasma protein characteristics,
      endogenous substances in plasma, total body and extracellular water, fat content,
      regional blood flow and probably P-glycoprotein, mainly that present in the gut,
      liver and brain. As far as drug metabolism is concerned, important differences
      have been found in the pediatric population compared with adults both for phase I
      enzymes [oxidative (e.g. cytochrome CYP3A7 vs. CYP3A4 and CYP1A2), reductive and
      hydrolytic enzymes] and phase II enzymes (e.g. N-methyltransferases and
      glucuronosyltransferases). Finally, key factors undergoing maturational changes
      accounting for differences in renal excretion in the pediatric population
      compared with adults are glomerular filtration and tubular secretion. It would be
      important to generate information on the developmental aspects of renal P
      glycoprotein and of other renal transporters as done and still being done with
      the different isozymes involved in drug metabolism.

PMID- 12803569
TI  - Gastrointestinal effects of nonsteroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) causes extensive damage to the
      gastrointestinal (GI) tract. The underlying mechanisms of gastric injury include
      topical irritant actions that disrupt the epithelial barrier, as well as the
      inhibition of cyclo-oxygenase (COX), which is predominantly the COX-1 isoform in
      the mucosa. This damage can be attenuated by antisecretory agents or by mucosal
      protective agents such as the synthetic prostanoids or nitric oxide (NO) donors.
      Compounds designed to attenuate topical irritancy, or have protective agents
      incorporated, such as NO-containing NSAIDs, the CINODs (cyclo-oxygenase
      inhibiting NO-donating drugs) show reduced mucosal injury. NSAIDs also cause
      injury in the small intestine, which appears to result from initial COX
      inhibition, with subsequent translocation of indigenous bacteria, induction of NO
      synthase and production of the cytotoxic moiety, peroxynitrite. The COX-2
      selective agents, the coxibs, which inhibit prostanoid biosynthesis at
      inflammatory sites, but not the endogenous protective prostanoids in the gut
      formed by COX-1, have proved so far to be a successful therapeutic approach to
      reducing NSAIDs GI damage. The clinical outcome of the use of the second
      generation of coxibs, and the newer NO NSAIDs is now awaited.

PMID- 12803570
TI  - Different vascular responsiveness to angiotensin II in two normotensive rat
      strains.
AB  - Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to
      present differences in stimuli responses involving the renin-angiotensin system
      and in cardiovascular responses to an acoustic startle stimulus. Here we compared
      the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred
      rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious
      rats, before and after a neurohumoral blockade obtained by successive
      administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor
      antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a
      constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280
      ng/kg were injected randomly. Average dose-response curves were established.
      After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3
      mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800
      microL/min, i.v.) were used to reflect arterial wall structure. The maximal
      systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were
      higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for
      SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type
      1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344
      and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP
      level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37
      +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response
      to ANG II mediated by AT1 receptors is compatible with a high number of AT1
      receptors in this strain. In F344, the exaggerated systolic and PP responses to
      ANG II and the higher MBP level after hydralazine most likely reflect a
      structural modification of the arterial wall such as hypertrophic remodelling in
      F344.

PMID- 12803571
TI  - Antihypertensive effects of the essential oil of Alpinia zerumbet and its main
      constituent, terpinen-4-ol, in DOCA-salt hypertensive conscious rats.
AB  - The present study investigated the hypotensive responses to intravenous (i.v.)
      treatment with the essential oil of Alpinia zerumbet (EOAZ) and its main
      constituent, terpinen-4-ol (Trp-4-ol), in the experimental model of
      deoxycorticosterone-acetate (DOCA)-salt hypertensive rat. In both DOCA-salt
      hypertensive and uninephrectomized, normotensive rats, i.v. bolus injections of
      EOAZ (1-20 mg/kg) or Trp-4-ol (1-10 mg/kg) decreased mean aortic pressure (MAP)
      in a dose-related manner. However, hypotensive responses to Trp-4-ol were
      significantly greater than those evoked by the same doses of EOAZ (1-10 mg/kg).
      Treatment with DOCA-salt significantly enhanced the maximal percentage decreases
      in MAP evoked by EOAZ or Trp-4-ol. Likewise, both maximal percentage and absolute
      decreases in MAP elicited by i.v. injection of the ganglion blocker,
      hexamethonium (30 mg/kg), were significantly greater in DOCA-salt hypertensive
      than in control rats. In DOCA-salt hypertensive rats, neither hexamethonium (30
      mg/kg, i.v.) nor methylatropine (1 mg/kg, i.v.) pretreatment affected the
      enhancement of EOAZ-induced hypotension. These results show that i.v. treatment
      with either EOAZ or Trp-4-ol dose-dependently decreases blood pressure in
      conscious DOCA-salt hypertensive rats, and this action is enhanced when compared
      with uninephrectomized controls. This enhancement could be related mainly to an
      increase in EOAZ-induced vascular smooth muscle relaxation rather than to
      enhanced sympathetic nervous system activity in this hypertensive model. The data
      further support our previous hypothesis that hypotensive effects of EOAZ are
      partially attributed to the actions of Trp-4-ol.

PMID- 12803572
TI  - Effect of drugs on cholesterol crystallization in an artificial bile model and
      relation of this effect to drug binding to albumin.
AB  - Substances that can affect the crystallization of cholesterol from human bile and
      consequently the gallstone formation have been given considerable attention. We
      improved the model system for testing cholesterol crystallization-affecting
      activity (promoting or inhibiting) of substances and used it for some drugs that
      are excreted into bile. Besides other factors natural lipid-protein complexes
      isolated from the native human bile have been shown to be responsible for
      nucleation and fast crystal growth in cholesterol supersaturated model bile.
      Artificial lipid-protein complex of taurolithocholate, human serum albumin and
      Ca2+ (TLTC-HSA-Ca2+) exhibited a lower crystallization activity than both the
      artificial lipid-protein complexes of taurodeoxycholate, human serum albumin and
      Ca2+ and the lipid-protein complex isolated from native human bile. The model
      bile supplemented with this artificial lipid-protein complex (TLTC-HSA-Ca2+)
      formed a convenient system for testing of various substances (drugs) for their
      crystallization-affecting activity. From the 20 tested drugs, which could occur
      at least in small amounts in human bile, the highest crystallization-promoting
      activity was found for complexes with ampicillin, butorphanol and colchicine.
      Complexes with tetracycline, thioridazine and doxycycline were the strongest
      inhibitors. The drugs, which had some effect on cholesterol crystallization,
      affected somehow the artificial lipid-albumin complex by displacing its
      components. Interactions of different drugs with HSA and its artificial complexes
      with the conjugated bile salt and Ca2+ ions were followed by absorption
      spectroscopy to observe displacement interactions. On the basis of these
      experiments we could classify drugs into four groups which differ by their
      effects on spectral characteristics of complexes.

PMID- 12803573
TI  - Ultrastructural clues for glutamate-induced necrosis in parietal and cerebellar
      neurons.
AB  - Glutamate excitotoxicity has been postulated to underlie the neuronal death that
      occurs after ischemia. The most sensitive tissues to ischemic injury are
      hippocampus and cerebellum, whereas cerebrum is more resistant. We studied the
      glutamate-induced ultrastructural alterations in rat parietal and cerebellar
      neurons comparatively. We observed that glutamate (45 min, 10-7 m) causes
      considerable nuclear, mitochondrial and cytoplasmic changes in both the neuron
      types. Mitochondrial and nuclear changes were particularly more severe in
      cerebellar granular, than the ones in parietal neurons. It has been concluded
      that glutamate induces necrotic changes in both parietal and cerebellar neurons.
      But cerebellar cortex was found to be more sensitive to glutamate excitotoxicity
      than cerebral cortex. We suggest that mitochondrial damage is, probably, an
      important factor in neuron necrosis, which is mediated by glutamate
      excitotoxicity.

PMID- 12803574
TI  - The [14C-N-methyl]-erythromycin breath test dosimetry complies with the French
      regulations for radiation safety.
AB  - The [14C-N-methyl]-erythromycin breath test (14C-ERMBT) is one of the most
      valuable probes for liver cytochrome P450-3A4 activity in humans. In order to
      extend the use of this test in France, we herein provide safety data regarding
      either patient dosimetry or worker exposure to [14C-N-methyl]-erythromycin. In
      order to determine the maximum radiation exposure for patient and nuclear
      medicine technician following one intravenous 14C-ERMBT [111 kiloBequerel (kBq)],
      we have used the dosimetric data gathered in animal studies and extrapolated to
      humans using a weight-based method, approximate data provided by the French
      Society of Radioprotection and erythromycin pharmacokinetics in humans,
      considering always the worst conditions for the patient and worker exposure
      determination. The radioactivity administered to a patient after one 14C-ERMBT
      was equal to 108.8 kBq (i.e. 98% of the total radioactivity in the 14C
      erythromycin vial) leading to a patient effective dose of 20 microsievert
      (microSv) and a maximum effective dose after 14CO2 inhalation by the exposed
      worker of 16 microSv compared with a mean individual annual effective dose from
      natural and artificial radioactivity exposure of 3500 microSv in France. The 14C
      ERMBT is safe and complies with the European regulations regarding the
      administration of 14C-labelled compounds in humans. It can therefore be used in
      clinical research in France without any particular safety requirement.

PMID- 12803575
TI  - Two novel methods for the determination of CYP1A2 activity using the
      paraxanthine/caffeine ratio.
AB  - Cytochrome P450 1A2 (CYP1A2) plays an important role in drug metabolism.
      Provocation with caffeine is used to estimate CYP1A2 activity, but in most tests
      a long period of caffeine abstinence has to be taken into account. We compared
      two novel methods with the currently applied test. The pharmacokinetic (PK)
      parameters of caffeine and paraxanthine were estimated in eight caffeine-taking
      healthy volunteers by fitting serum concentration-time data to a two-compartment
      PK model. Then a three-step approach was followed. Step 1: The caffeine
      administration regimens of three provocation methods, which differ by their
      periods of abstinence, together with the PK parameters of each volunteer, were
      entered in a PK simulation program and the molecular ratio of the
      paraxanthine/caffeine concentration (P/C molratio) of each method was estimated
      for the individual volunteers. Step 2: For each method a relationship for the
      population between the caffeine clearance (Clc) and the corresponding P/C
      molratio was empirically established. Step 3: The true caffeine clearance (Clc
      tr) of each volunteer, as found by fitting the individual PK curve, was compared
      for all three methods with the clearance estimated from the individual P/C
      molratio using the relationship of step 2. The predictive values for Clc of the
      three methods did not differ significantly from Clc tr. For the three methods the
      values for bias were 6.7, 4.3 and 3.1%, respectively and for precision they were
      12.3, 20.6 and 17.8%. We conclude that the two novel methods of caffeine
      provocation show good predictive performance for Clc when compared with the
      conventional method. Abstaining from caffeine for a long period is not necessary
      to estimate CYP1A2 activity (using the P/C molratio) accurately.

PMID- 12803576
TI  - Differences in the effects of extended-release aspirin and plain-formulated
      aspirin on prostanoids and nitric oxide in healthy volunteers.
AB  - This study was designed to evaluate the effects of extended-release aspirin on
      platelet aggregation and the production of prostanoids and nitric oxide. The
      participants in this double blind, randomized and crossover study were 20 healthy
      volunteers. Interventions were 150 mg of plain-formulated aspirin (PFASA) and 150
      mg of extended-release aspirin (ERASA). Blood samples were collected before and
      10, 20, 60, 120, 240, 480 and 1440 min after the first dose; 3, 7 and 14 days
      after daily administration and 24 h after the last dose. The main measures were
      platelet aggregometry, thromboxane B2, 6-keto-prostaglandin (PG) F1alpha and
      nitric oxide in each control. Platelet aggregation was inhibited by 50% with
      ERASA, and by 77% with PFASA. No differences were found in chronic treatment.
      Thromboxane B2 was inhibited more by the latter (51-67%), but 90% inhibition was
      observed in both groups after 3 days. The levels of 6-keto-PGF1alpha was reduced
      by 20% with ERASA and by 58% with PFASA. Nitric oxide production increased in
      both groups, but after 24 h, and 7-14 days, elevated concentrations of nitric
      oxide were found only in the ERASA. The antiplatelet effects of ERASA provide
      pharmacological advantages (greater prostacyclin synthesis and prolonged increase
      in nitric oxide production) over those provided by the plain formulation.

PMID- 12803577
TI  - Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French
      populations.
AB  - Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the
      metabolism of different drugs with low therapeutic index such as oral
      anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic
      allelic variants. The frequency of these alleles in different ethnic populations
      is extremely variable. In this study, we compared the frequencies of CYP2C9
      allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians
      living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and
      the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1,
      CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as
      lower as the French subjects, but three times higher than Korean (0.036 vs.
      0.011). The CYP2C9*2 allele could be detected in only one Chinese subject,
      whereas it represented the major allelic variant in French Caucasians. The low
      frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does
      not justify their detection in clinical practice, unlike French Caucasians.

PMID- 12803578
TI  - Caffeine as a promoter of analgesic-associated nephropathy--where is the
      evidence?
AB  - Individual groups of nephrologists - in their responsibility for their patients -
      initiated a most controversial discussion whether or not caffeine - coformulated
      to analgesics - might initiate or sustain analgesic overdosing. The original
      sources (data) of such suspicion have got lost during the debate of the last two
      decades. Therefore, it seemed to be appropriate to investigate the original data
      background and the reasons why nephrologists started to suspect caffeine as a
      stimulant of analgesic overdosing by employing a systematic and exhaustive review
      of primary nephrological publications. Their selection followed a precise
      selection plan, including all epidemiological studies on analgesic-associated
      nephropathy, the original papers of all groups having been involved in those
      studies, further originals from the mainly involved countries (academically,
      politically), and any literature thereof cited as a proof. The following results
      emerged from the investigation: (i) The epidemiological studies warranted no
      conclusion about a role of caffeine in prompting excessive analgesic use. (ii)
      The identified groups of nephrologists provided not substantial data to advocate
      the said suspicion, except for the observation of a preferential choice of
      phenacetin-containing combinations, especially powder preparations. (iii) Only
      two cited original data sources revealed drug-seeking behaviour with phenacetin
      containing preparations which subsided, after phenacetin was banned from the
      respective markets. Conclusively, it appears that there is no substantial data to
      support a pivotal role of caffeine in initiating or sustaining analgesic
      overdosing. However, there is strong data that phenacetin, by its psychotropic
      properties, may have caused drug-seeking behaviour and thus led to analgesic
      overdosing. This conclusion is convincingly supported by thorough pharmacokinetic
      investigations. Note: All caffeine-related statements within the reviewed
      literature have been collected in tables (referred to as Table SX) which are
      provided in full text for check on the following website:
      http://www.blackwellpublishing.com/products/journals/suppmat/FCP/FCP174/FCP174sm.
      tm

PMID- 12803579
TI  - Free radicals and cardiac arrhythmias following coronary surgery: actors of the
      drama or bystanders of the spectacle?

PMID- 12803580
TI  - Cardiac complications after elective major vascular surgery.
AB  - Cardiac complications are the major cause of perioperative and late mortality and
      morbidity in patients undergoing elective major vascular surgery. This review
      focuses on the pathophysiology of perioperative complications, risk assessment
      and risk reduction strategies, all related to cardiovascular disease. Patients
      without cardiac risk factors are considered to be at low risk and no additional
      evaluation for coronary artery disease is recommended; beta-adrenergic blockers
      may reduce perioperative cardiac events; patients with one or more risk factors
      represent an intermediate to high-risk population. beta-Adrenergic blockers
      should be prescribed to all patients and coronary revascularization should be
      reserved for patients who have a clearly defined need for revascularization
      independent of the need for vascular surgery.

PMID- 12803581
TI  - Citation classics in anaesthesia and pain journals: a literature review in the
      era of the internet.
AB  - BACKGROUND: The number of citations an article receives reflects its scientific
      impact. The introduction of internet-based resources to search and access
      articles has made it possible to review even whole scientific areas. This study
      identifies the top 50 most-cited articles over the last 25 years in specialty
      journals dedicated to anaesthesia and pain, respectively. METHODS: Twenty-two
      journals listed in The Science Citation Index Expanded in the field of
      anaesthesiology and nine major medical journals were screened using the cited
      reference option to identify articles cited more than 100 times between 1986 and
      2002. The top 50 articles in specialty journals and the top 10 articles in major
      medical journals concerning anaesthesia and pain were retrieved for further
      analysis. RESULTS: The most-cited articles in specialty journals were published
      from 1986 to 1997 and received a mean of 222 (anaesthesia) and 279 (pain)
      citations. Sixty-seven institutions produced the most-cited articles and of those
      28 were located outside North America. The articles were published in six
      journals led by the Journal of Pain (50 articles) and Journal of Anaesthesiology
      (39 articles). Forty-seven articles were classified as related to clinical
      experience, 33 were review articles, and 20 discussed basic science. CONCLUSION:
      To make an article a possible 'citation classic' in anaesthesiology, it should be
      published in one of six leading journals and originate from an established
      institute in North America. Internet resources to publish and cite the literature
      have to date not advanced any article published in the last 5 years to the top
      100 list.

PMID- 12803582
TI  - The work, duties and prestige of Finnish anesthesiologists: patients' view.
AB  - BACKGROUND: Patients' awareness of the medical qualifications and duties of
      anesthesiologists outside the operating theatres may be limited. How are
      anesthesiologists ranked with regard to prestige and academic qualifications
      among other hospital employees? METHODS: One hundred and sixty operative patients
      were interviewed in one tertiary care center and another secondary care center in
      Finland. RESULTS: Nearly all (90%) of the patients knew that anesthesiologists
      are medical doctors and that they work in operation theatres (87%). Many patients
      thought that anesthesiologists do not work in pain clinics (41%), obstetric
      departments (36%) and in the departments of radiology (68%), in ambulances (58%)
      and in research work (46%). Anesthesiologists were ranked second after surgeons
      with regard to prestige among health service professionals. CONCLUSIONS: Patients
      knew the medical qualification of anesthesiologists very well. The work of
      anesthesiologists was highly appreciated, but the duties outside the operation
      theatres were poorly known.

PMID- 12803584
TI  - Detection of organ ischemia during hemorrhagic shock.
AB  - BACKGROUND: In a porcine hemorrhagic shock model we aimed to determine: (a)
      whether blood flow to the intestine and kidney was more reduced than cardiac
      output; (b) whether parameters of anaerobic metabolism correlated with regional
      blood flow; and (c) whether metabolic parameters in intestine, kidney and
      skeletal muscles detected a compromised metabolic state at an earlier stage than
      did systemic parameters. METHODS: In an animal research laboratory at a
      university hospital six domestic pigs were subjected to volume-controlled
      hemorrhage. Every 30 min samples of blood were withdrawn. Systemic and regional
      hemodynamic parameters and tissue levels of PCO2 were monitored. Whole body and
      organ-specific oxygen consumption (VO2) and veno-arterial (VA) differences of
      lactate, glucose, potassium (K+), PCO2, H+ and base excess (BE) were calculated
      every 30 min. RESULTS: With progressive hemorrhage, intestinal blood flow
      decreased to the same extent as cardiac output, whereas the reduction in renal
      blood flow was more pronounced. We found a concomitant reduction in VO2 (onset of
      supply dependent metabolism) in intestine, kidney and skeletal muscles. In
      muscular tissue PCO2 increased to levels three times higher than baseline, while
      renal and intestinal PCO2 increased eightfold. Supply dependency was associated
      with a concomitant increase in VA CO2 and VA H+. Also, VA lactate increased,
      mostly in intestine and least in skeletal muscle. Intestinal and renal VA K+
      increased, while muscular VA K+ decreased. Arterial lactate and H+ increased
      considerably, whereas arterial BE decreased. CONCLUSION: With progressive
      hemorrhage, renal blood flow, but not intestinal and skeletal muscle blood flow,
      was reduced more than cardiac output. Supply dependent oxygen metabolism (VO2)
      and organ acidosis occurred simultaneously in the three organs, despite
      differences in blood flow reductions. Organ ischemia coincided with a pronounced
      change in arterial lactate and systemic acid base parameters.

PMID- 12803583
TI  - Effects of different steroid treatment on reperfusion-associated production of
      reactive oxygen species and arrhythmias during coronary surgery.
AB  - BACKGROUND: During conventional cardiac surgery ischemia and reperfusion may
      cause excessive production of reactive oxygen species leading to tissue damage
      including early arrhythmias. We therefore assessed the kinetics of markers of
      radical stress including oxidized and reduced glutathione (GSSG/GSH), oxidized
      proteins (PCG) and malondialdehyde (MDA), and tested the hypothesis that
      different steroid treatments inhibit these markers and early reperfusion
      associated supraventricular and ventricular extrasystolic beats. METHODS: In a
      randomized, controlled, blinded, prospective trial 36 patients received a
      preoperative infusion of methylprednisolone (MP, 15 mg kg-1, n = 12), tirilazad
      mesylate (TM, 10 mg kg-1, n = 12) or placebo (PL, NaCl, n = 12). Coronary sinus
      and arterial blood was drawn at baseline and 2, 5, 15, 30, 60 and 240 min after
      aortic declamping. Holter-ECG analysis was used to identify arrhythmias. RESULTS:
      Cardiac GSSG release occurred very early (< 15 min) and was not significantly
      attenuated by either drug treatment. Cardiac PCG production showed biphasic
      increases, lasted > 4 h and was significantly reduced only by TM. Cardiac MDA
      release was short (< 30 min) and significantly reduced by MP and TM. Neither
      treatment had a significant influence on the early occurrence of ventricular or
      supraventricular arrhythmias. The number of patients needing cardioversions or
      defibrillations also were not different. CONCLUSIONS: The results indicate that
      cardiac production of reactive oxygen species occurs after reperfusion in humans
      and is not inhibited by steroid treatment. Steroid treatment effectively reduces
      lipid peroxidation during cardiac surgery but has no influence on arrhythmias.

PMID- 12803585
TI  - Recombinant human erythropoietin in preoperative autologous blood donation did
      not influence the haemoglobin recovery after surgery.
AB  - BACKGROUND: Recombinant human erythropoietin in combination with preoperative
      autologous blood donation is an established regime for avoiding allogenic blood
      transfusions. The aim of the study was to determine endogenous erythropoietin
      production and haemoglobin recovery after preoperative autologous blood donation
      and surgery, with or without recombinant human erythropoietin treatment. METHODS:
      Thirty-eight patients having total hip joint replacement surgery were randomised
      to receive either autologous blood transfusion (control group) or autologous
      transfusion plus preoperative recombinant human erythropoietin treatment (EPO
      group). Haemoglobin, haematocrit, erythropoietin and reticulocyte concentrations
      were repeatedly analysed, before, during, and after surgery. RESULTS: No
      significant differences were found between the groups regarding haemoglobin,
      haematocrit, and erythropoietin, but the reticulocyte count increased
      significantly more in the EPO group. There was no difference in the requirement
      for allogeneic blood transfusions between the groups. The baseline haemoglobin
      was >13 g dL-1 in all but four patients. CONCLUSIONS: In patients with normal
      preoperative haemoglobin levels, recombinant human erythropoietin treatment did
      not improve haemoglobin levels, or reduce the need for allogenic blood
      transfusion. There were no differences in serum erythropoietin concentrations
      between the groups. We question whether recombinant human erythropoietin
      treatment facilitates preoperative autologous blood donation in patients with
      normal haemoglobin levels.

PMID- 12803586
TI  - A practice survey on vasopressor and inotropic drug therapy in Scandinavian
      intensive care units.
AB  - BACKGROUND: This practice survey was performed to analyse the indications for use
      of vasopressor/inotropic drugs, preferred drugs and doses as well as concomitant
      monitoring and desired haemodynamic target values in Scandinavian ICUs. An
      internet-based reporting system was implemented. METHODS: A total of 223 ICUs
      were identified in the Scandinavian countries and invited to participate in a one
      day point-prevalence study. An internet-based database was constructed and a
      practice survey protocol designed to identify haemodynamic monitoring,
      indications for vasopressor/inotropic drug-therapy, fluids used for volume
      loading, pretreatment circulatory state, actual and targeted haemodynamic
      variables. Patients were eligible for the study if on vasopressor/inotropic drug
      therapy for more than 4 h. RESULTS: A total of 114 ICUs participated. A total of
      114 adult patients matched the inclusion criteria. Sixty-seven per cent of the
      patients had received vasopressor/inotropic drug-treatment for >24 h and 32%
      received more than one drug. Arterial hypotension (92%) and oliguria (50%) were
      most common indications. Fluid loading prior to therapy was reported in 87% of
      patients. Dopamine (47%) and noradrenaline (44%) were the most commonly used
      drugs followed by dobutamine (24%). No other drug exceeded 6%. Non-catecholamine
      drugs were rarely used even in cardiac failure patients. Invasive arterial
      pressure was monitored in 95% of patients, pulmonary artery catheters were used
      in 19%. Other cardiac output monitoring techniques were used in 8.5% of the
      patients. CONCLUSION: Dopamine and noradrenaline seem to be the most commonly
      used inotropic/vasopressor drugs in Scandinavia. Traditional indications for
      inotropic/vasopressor support as hypotension and oliguria seem to be most common.
      Invasive monitoring was used in almost all patients, whereas a limited use of
      pulmonary artery catheters was noted. The internet-based reporting system proved
      to be an efficient tool for data collection.

PMID- 12803587
TI  - Respiratory burst activity of polymorphonuclear cells is dependent on the cell
      preparation technique.
AB  - BACKGROUND: Controversial results have been reported regarding the effect of
      anaesthetics on superoxide anion production during the respiratory burst (RB) of
      polymorphonuclear cells (PMN). The differences could be caused by the cell
      preparation methods and the aim of this study was to compare two techniques.
      METHODS: RB activity was measured in cell suspensions isolated with the single
      step Ficoll procedure and in unfractionated whole blood. Two concentrations of
      propofol (therapeutic and 10-fold of this, 6 microg ml-1 or 60 microg ml-1) were
      investigated after cell preparation with both methods. RB was stimulated with
      Escherichia coli (E. coli), phorbol 12-myristate 13-acetate (PMA) or N-formyl
      methionyl-leucyl-phenylalanine (fMLP) and measured by means of fluorescence
      intensity in a flow cytometer. RESULTS: The percentage of PMNs in whole blood
      which generate superoxide anions in response to fMLP was significantly lower (2.5
      +/- 0.7%; mean +/- SEM) than that in Ficoll isolated cell suspensions (15.1 +/-
      1.7%). Incubation with propofol led to a concentration-related decrease of RB
      activity in Ficoll separated PMNs after both PMA and fMLP stimulation. No
      significant effect of propofol was observed on the RB in PMA stimulated whole
      blood samples. CONCLUSION: The results suggest that the influence of cell
      preparation methods should be considered when the in vitro effects of
      anaesthetics on PMN functions are studied with flow cytometric methods.

PMID- 12803588
TI  - Low plasma glutamine after multiple trauma: relationship with intracellular
      glutamine in polymorphonuclear neutrophils during prolonged ICU stay.
AB  - BACKGROUND: Aim of the study was to evaluate whether low plasma glutamine (GLN)
      is related to low intracellular GLN in stress-affected cells such as
      polymorphonuclear neutrophil (PMN). We hypothesized, that because low plasma GLN
      is assumed to have an impact on clinical outcome, stress-affected cells may also
      show low GLN contents. METHODS: Thirty-nine consecutive severely injured trauma
      patients staying at least 10 days at a surgical intensive care unit (ICU) of a
      university hospital were separated into two groups: group one (n = 16) with low
      plasma GLN (< 420 micromol/l in average during ICU stay), and group two (n = 23)
      with normal plasma GLN. Initial blood samples for GLN analyses were collected
      within 24 h of admission at ICU. Further blood samples were taken on days 5 and
      10 at 08:00 hours. RESULTS: Patients in both groups showed no differences
      regarding demographic data, surgical interventions or infections. Acute
      physiology and chronic health evaluation (APACHE) II and the sequential organ
      failure assessment (SOFA) score and mortality rate were also comparable. During
      the study period, intracellular PMN GLN contents and concentrations did not
      differ between both groups. On the first day, intracellular PMN GLN content in
      the low plasma GLN group peaked at 5.01 +/- 3.06 x 10(-16) mol and in normal
      plasma GLN group at 4.73 +/- 2.57 x 10(-16) mol above the level of healthy
      individuals. In both groups, content decreased significantly towards the end of
      the observation period (group one: 2.79 +/- 1.59 x 10(-16) mol and group two:
      2.63 +/- 1.71 x 10(-16) mol). A correspondent course could be observed for cell
      volumes. In contrast, variation of intracellular GLN concentrations remained
      within the reference range throughout the observation period: group one 836 +/-
      510 micromol/l on day 1 and 582 +/- 331 micromol/l on day 10, and group two 788
      +/- 428 micromol/l on day 1 and 548 +/- 356 micromol/l on day 10. No correlation
      between plasma GLN and intracellular GLN was found in either group. CONCLUSION:
      No association between low plasma GLN and low intracellular GLN in PMN was found
      in a cohort of severely injured trauma patients with a minimum stay of 10 days at
      ICU.

PMID- 12803590
TI  - Is there a risk of sensitization and allergy to chlorhexidine in health care
      workers?
AB  - BACKGROUND: In Denmark, chlorhexidine is the standard disinfectant in most
      hospitals and health care workers are repeatedly exposed to it. The aim of this
      study was to establish whether there is a risk of sensitization and allergy to
      chlorhexidine from this type of exposure. METHODS: Two hundred and forty-eight
      doctors, nurses and auxiliary staff were invited to participate in the study. One
      hundred and four individuals took part in the full study including skin tests and
      a questionnaire and a further 74 individuals filled in the questionnaire giving a
      total of 178 questionnaires (72%). Patch tests with chlorhexidine gluconate 1%
      and chlorhexidine acetate 1% were performed looking for type IV (delayed type)
      allergy. A prick test with chlorhexidine gluconate 0.5% and an intradermal test
      with chlorhexidine 0.0002% were performed looking for type I (immediate type)
      allergy. RESULTS: There were no positive tests in any of the 104 individuals
      tested (99% confidence interval 0-4.9%). There was a predominance of females in
      both groups and the overall median age was 42 years (28-63). No one in the group
      not tested reported to have a verified or suspected allergy to chlorhexidine.
      CONCLUSION: In this first study to examine the risk of type I and type IV allergy
      to chlorhexidine in health care workers with daily exposure to chlorhexidine, we
      did not identify allergies to chlorhexidine in any of the 104 individuals tested
      or in the additional 74 individuals who completed the questionnaire. We conclude
      that an allergy to chlorhexidine in health care workers is likely to be rare.

PMID- 12803589
TI  - Milrinone improves lung compliance in patients receiving mechanical ventilation
      for cardiogenic pulmonary edema.
AB  - BACKGROUND: Cardiogenic pulmonary edema is a frequent cause of respiratory
      failure. We investigated whether milrinone improved lung compliance. METHODS: We
      selected 10 patients with respiratory failure due to severe cardiogenic pulmonary
      edema to receive mechanical ventilation. Patients were administered a bolus
      injection of milrinone (50 microg kg-1) over 10 min, followed by continuous
      intravenous infusion (0.5 microg kg-1 min-1). Lung compliance, blood gas values,
      hemodynamic parameters, and sample plasma milrinone levels were assessed over 120
      min after the onset of the continuous infusion of milrinone. RESULTS: Ten min
      following milrinone infusion, dynamic compliance (Cdyn) and static compliance
      (Cst) increased from 37 +/- 12 to 42 +/- 12 ml cmH2O-1 and from 40 +/- 13 to 45
      +/- 12 ml cmH2O-1, respectively (P < 0.01). Plasma milrinone levels reached a
      therapeutic level for vasodilator and positive inotropic effect at 10 min after
      milrinone infusion. A significant decrease in mean pulmonary artery pressure and
      pulmonary artery wedge pressure occurred simultaneously with an increase in
      respiratory system compliance. However, an increase in cardiac index was observed
      later than these changes. There were significant correlations between the mean
      pulmonary artery pressure and Cdyn (r = -0.39, P < 0.01) and Cst (r = -0.38, P <
      0.01). CONCLUSIONS: Milrinone-induced improvement in lung compliance along with
      an improvement of hemodynamics was found together with an inverse relationship
      between compliance and mean pulmonary artery pressure.

PMID- 12803591
TI  - Influences on serum concentrations of morphine, M6G and M3G during routine
      clinical drug monitoring: a prospective survey in 300 adult cancer patients.
AB  - BACKGROUND: In order to make treatment decisions physicians should have knowledge
      about the relations between patient characteristics and drug disposition. Dose,
      route of administration, gender, age and renal function are reported to influence
      the serum concentrations of morphine, morphine-6-glucurnide (M6G) and morphine-3
      glucuronide (M3G) during chronic treatment of cancer pain. These factors,
      however, are not evaluated in studies with a sample size sufficient to explore
      predictive factors. METHODS: Three hundred consecutive morphine users admitted
      because of a malignant disease were recruited. The relations of serum
      concentrations of morphine, M6G and M3G to patient characteristics (gender, age,
      weight, renal function, liver function, dose, route of administration) were
      explored, and regression analysis performed to investigate whether these
      characteristics predicted serum concentrations obtained during routine clinical
      drug monitoring. RESULTS: Morphine dose was associated with serum concentrations
      of morphine (r = 0.69), M6G (r = 0.76) and M3G (r = 0.76). Oral morphine resulted
      in higher dose-adjusted M6G and M3G serum concentrations compared with s.c.
      morphine. Creatinine serum concentrations correlated with serum concentrations of
      M6G and M3G. Dose and route of administration predicted morphine serum
      concentrations, while dose and renal function predicted M6G and M3G serum
      concentrations. Age was an additional factor predicting M3G concentrations. Dose
      was the only factor that explained a clinically significant part of the observed
      variability. CONCLUSION: Patient characteristics predict only minor parts of the
      variability of morphine, M3G and M6G serum concentrations observed during routine
      clinical drug-monitoring in cancer patients.

PMID- 12803592
TI  - Effective pain relief from intra-articular saline with or without morphine 2 mg
      in patients with moderate-to-severe pain after knee arthroscopy: a randomized,
      double-blind controlled clinical study.
AB  - BACKGROUND: Intra-articular (IA) morphine has given good and prolonged pain
      relief in some studies when given at the end of arthroscopic procedures in the
      knee joint. However, similar studies have not been able to document any local
      analgesic effect of morphine. A large number of the negative studies have not
      demonstrated any assay sensitivity. We have documented that around 40% of
      patients have only very mild or no pain after arthroscopic procedures in the knee
      joint. This obviously is a confounding factor, reducing assay sensitivity when
      all patients are included in IA morphine studies. METHOD: By leaving a soft
      catheter IA in 57 patients and including only patients who developed moderate-to
      severe pain within 1 h after an arthroscopic procedure in the knee joint under
      general anaesthesia, we included 40 patients. These patients had a mean pre
      treatment baseline pain of about 50/100 on a 100-mm visual analogue scale (VAS)
      for pain intensity. A randomized, double-blind controlled comparison of saline 10
      ml with or without morphine 2 mg followed. Test drugs were administered through
      the IA catheter. Pain intensity and pain relief, consumption of rescue analgesics
      and global evaluation of effect and adverse effects were measured up to 36 h
      thereafter. RESULTS: Pain intensity decreased from about 50 to about 10-15/100 in
      both groups and the sum of pain intensity differences at 2 and 22 h was not
      significantly different between the two groups. Global evaluation of effects and
      adverse effects, as well as consumption of rescue analgesics during 36 h after
      arthroscopic procedures, were also similar in the two groups. CONCLUSIONS: Only
      70% of 57 patients had pain of moderate-to-severe intensity within 1 h after an
      arthroscopic procedure of the knee joint under general anaesthesia. IA injection
      of saline 10 ml and saline 10 ml with morphine 2 mg were both associated with
      pain relief. These findings may have implications for interpretations of a
      majority of published studies on IA morphine.

PMID- 12803593
TI  - EMLA does not permit pain-free retrobulbar injection.
AB  - BACKGROUND: Retrobulbar injection can be associated with significant pain, due to
      both needle insertion and deposition of the local anaesthetic solution. The local
      anaesthetic cream EMLA (eutectic mixture of local anaesthetics) which contains a
      mixture of lignocaine and prilocaine has been shown to reduce the pain associated
      with skin puncture. The efficacy of EMLA in alleviating the pain of retrobulbar
      injection for cataract surgery was assessed in this study. METHODS: In this,
      randomised double-blind study, EMLA (n = 53) or lignocaine 5% ointment (n = 50)
      was administered to the inferior orbital margin at least 45 min before
      retrobulbar block in 103 patients. Pain assessed during retrobulbar block was
      marked subjectively by the patient on a 10-point numerical rating scale. RESULTS:
      Median verbal pain scores were 3.0 with an interquartile range of 1.5-6.5 in the
      control group and 3.50 with an interquartile range of 2.0-6.0 in the EMLA(R)
      group (P = 0.67). There was no significant difference between the EMLA group and
      the lignocaine ointment group according to this pain assessment. CONCLUSION: EMLA
      does not permit pain-free retrobulbar injection.

PMID- 12803595
TI  - Effects of intra-abdominal CO2-insufflation on normal and impaired myocardial
      function: an experimental study.
AB  - BACKGROUND: Intra-abdominal pressure (IAP) elevation during CO2-pneumoperitoneum
      increases cardiac afterload and may enhance dysfunction of the already
      compromised heart. This study focused on the effects of acute IAP increases on
      left and right ventricular loadings and contractility in the heart with impaired
      global function. METHODS: Impairment of myocardial function (IMF) was
      pharmacologically induced in 16 pigs by administration of halothane and
      propranolol, while baseline arterial pressure was maintained by intravenous
      phenylephrine. Intra-abdominal pressure was gradually increased by 10 mmHg up to
      30 mmHg in the supine position (IMF group 1, n = 8) or in a head-down tilted
      position (IMF group 2, n = 8). In two control groups with normal myocardial
      function, IAP was also increased in the supine position or the head-down tilted
      position. Cardiac function in all groups was assessed by epicardial
      echocardiography, intraventricular pressure measurements and pulmonary artery
      catheterization. RESULTS: The increase in IAP was accompanied by a transient rise
      in LV end-systolic wall stress and reduced cardiac output significantly by 16-24%
      in all groups. In the IMF groups, LV end-diastolic transmural pressure increased
      by 34-60% to peak values of 24 mmHg, while cross-sectional LV end-diastolic areas
      remained unchanged. Increases in right ventricular end-diastolic volume and
      decreases in right ventricular ejection fraction as well as in cardiac output
      were most pronounced at IAP 20 mmHg and significantly stronger in both IMF groups
      than in the control groups (P < 0.001). CONCLUSION: Following the acute elevation
      of IAP, the right ventricular volume load shifted more extensively in the IMF
      groups than in the animals with normal myocardial function. Myocardial function
      in the impaired heart may worsen during IAP elevation due to right ventricular
      load alterations rather than a LV afterload increase.

PMID- 12803594
TI  - Intraoperative changes in arterial oxygenation during volume-controlled
      mechanical ventilation in modestly obese patients undergoing laparotomies with
      general anesthesia.
AB  - BACKGROUND: In obese patients, arterial oxygenation can be greatly impaired
      during general anesthesia. Both avoidance of denitrogenation and application of
      positive end-expiratory pressure (PEEP) during mechanical ventilation may be
      effective in preventing such impairment of arterial oxygenation. METHODS: We
      studied 28 obese/overweight and seven non-obese (BMI < 25 kg x m-2) patients who
      underwent laparotomies with general anesthesia (i.e. isoflurane with or without
      nitrous oxide). During anesthesia, their lungs were mechanically ventilated at a
      rate of 10 breaths x min-1 with a constant flow, inspiratory-to-expiratory ratio
      1 : 2, and tidal volume approximately 10 ml x kg-1. The obese/overweight patients
      were allocated to four different groups in terms of denitrogenation and
      application of PEEP (7 cm H2O) during the ventilation (n = 7 each). In the non
      obese patients, their denitrogenated lungs were ventilated without application of
      PEEP. Arterial gas analyses were performed before induction of anesthesia, and
      30, 90, 150 and 210 min after tracheal intubation. The ratio of PaO2 to FiO2 was
      calculated as an index of arterial oxygenation. RESULTS: No significant changes
      in the PaO2/FiO2 ratio were observed throughout the study in the non-obese
      patients and in the obese/overweight patients whose non-denitrogenated lungs were
      ventilated with PEEP. In the obese/overweight patients whose lungs were
      ventilated after denitrogenation or without application of PEEP, significant
      decreases in the PaO2/FiO2 ratio were observed 30 and 90 min after tracheal
      intubation. CONCLUSIONS: In obese or overweight patients under general
      anesthesia, it may be advisable to avoid denitrogenation and apply PEEP during
      mechanical ventilation in order to minimize the impairment of arterial
      oxygenation.

PMID- 12803596
TI  - Resistive load of laryngeal mask airway and ProSeal laryngeal mask airway in
      mechanically ventilated patients.
AB  - BACKGROUND: The ProSeal Laryngeal Mask Airway (PLMA) ventilation tube is narrower
      and shorter than the standard Laryngeal Mask Airway (LMA) and is without the
      vertical bars at the end of the tube. In this randomized, crossover study, PLMA
      and LMA resistances were compared. METHODS: Respiratory mechanics was calculated
      in 26 anesthetized, mechanically ventilated patients with both LMA and PLMA. The
      laryngeal mask positioning was fiberoptically evaluated. Differences in the
      respiratory mechanics of the LMA and the PLMA were attributed to the differences
      between the laryngeal masks. RESULTS: In the total study population the airway
      resistance was 1.5 +/- 2.6 hPa.l-1.s-1 (P = 0.005) higher with the PLMA than with
      the LMA. During the PLMA use, the peak expiratory flow reduced by 0.02 +/- 0.05 l
      min-1 (P = 0.046), the expiratory resistance increased by 0.6 +/- 1.3 hPa.l-1.s-1
      (P = 0.022), and the time constant of respiratory system lengthened by 0.09 +/-
      0.18 s (P = 0.023). These differences doubled when the LMA was better positioned
      than the PLMA, whereas they disappeared when the PLMA was positioned better than
      the LMA. CONCLUSIONS: The standard LMA offers a lower resistive load than the
      PLMA. Moreover, the fitting between the laryngeal masks and the larynx, as
      fiberoptically evaluated, plays a major role in determining the resistive
      properties of these devices.

PMID- 12803597
TI  - Concordance between trifluoroacetic acid and hepatic protein trifluoroacetylation
      after disulfiram inhibition of halothane metabolism in rats.
AB  - BACKGROUND: Cytochrome P4502E1(CYP2E1)-mediated oxidation of halothane to a
      reactive intermediate (trifluoroacyl chloride) that covalently binds to hepatic
      proteins forming trifluoroacetylated neoantigens is believed to be the initiating
      event in a complex immunologic cascade culminating in antibody formation and
      severe hepatic necrosis ('halothane hepatitis') in susceptible patients.
      Trifluoroacyl chloride may also hydrolyze to the stable metabolite
      trifluoroacetic acid (TFA). CYP2E1 inactivation by disulfiram or its primary
      metabolite, diethyldithiocarbamate, inhibits human halothane oxidation to TFA in
      vitro and in vivo. Nevertheless, disulfiram effects on hepatic protein
      trifluoroacetylation by halothane in vivo are unknown. This investigation tested
      the hypotheses that disulfiram prevents halothane-dependent protein
      trifluoroacetylation in vivo, and that TFA represents a biomarker for hepatic
      protein trifluoroacetylation. METHODS: Rats were pretreated with isoniazid
      (CYP2E1 induction), isoniazid followed by disulfiram (CYP2E1 inhibition), or
      nothing (controls), then anesthetized with halothane or nothing (controls).
      Plasma and urine TFA were quantified by ion HPLC; hepatic microsomal TFA-proteins
      were analyzed by Western blot. RESULTS: CYP2E1 induction increased both TFA and
      TFA-protein formation compared with uninduced halothane-treated rats. Disulfiram,
      even after CYP2E1 induction, nearly abolished both TFA and TFA-protein formation.
      Pretreatments similarly affected both TFA and TFA-protein formation across all
      groups. CONCLUSIONS: Disulfiram inhibition of CYP2E1-mediated halothane oxidation
      prevents hepatic protein trifluoroacetylation. Based on the concordance between
      TFA and TFA-protein formation, TFA appears to be a valid biomarker for TFA
      protein formation. Disulfiram inhibition of human halothane oxidation in vivo,
      previously assessed by diminished TFA formation, probably also confers inhibition
      of hepatic TFA-protein formation.

PMID- 12803598
TI  - Fentanyl decreases propofol requirement for laryngeal mask airway insertion.
AB  - BACKGROUND: Since fentanyl is a potent depressant of the upper airway reflex,
      preadministration of fentanyl may facilitate insertion of the laryngeal mask
      airway (LMA) using propofol. Accordingly, we tested the hypothesis that fentanyl
      pretreatment would reduce the dose of propofol required for the LMA insertion.
      METHODS: Forty-one healthy patients without sedative premedication were randomly
      assigned to either fentanyl group, receiving fentanyl 2 microg kg-1
      intravenously, or control group, receiving equal volumes of normal saline. Then,
      3 ml of 2% lidocaine was given intravenously to alleviate pain associated with
      propofol administration. Thirty s after the fentanyl or saline injection, a
      predetermined dose of 1% propofol was given at a rate of 100 mg min-1. Insertion
      of the LMA was attempted 90 s after the completion of the propofol injection. The
      dose of propofol given to a particular patient was determined by the response of
      the preceding patient in that group to a higher or lower dose, using the up-and
      down method. The first patient in each group received 2.5 mg kg-1 of propofol,
      while the step-size was 0.25 mg kg-1. Patients responses were assessed by a
      blinded observer. RESULTS: ED50 and ED95 of propofol requirements were
      significantly less in the fentanyl group (0.82, 1.17 mg kg-1, respectively) than
      those in the control group (2.39, 2.62 mg kg-1, P < 0.001). CONCLUSION: Our
      results indicate that preadministration of fentanyl 2 microg kg-1 decreases the
      propofol requirement for the LMA insertion.

PMID- 12803599
TI  - Aseptic meningitis during combined continuous spinal and epidural analgesia.
AB  - Continuous spinal analgesia (CSA) offers considerable advantages: (1) it requires
      10% of the local anesthetic; (2) it may be instituted after patient positioning,
      thus minimizing the potential for cardiovascular instability; and (3) with low
      doses of dilute short-acting local anesthetic, the recovery period is shortened
      (1). Continuous spinal analgesia has been used for various procedures such as
      surgery and cancer pain control. However, CSA has not gained wide popularity
      because of its possible complications, such as headache, nerve injury, infection
      and accidental removal or migration of the catheter. Although real possibilities,
      these complications have been rarely documented. We describe an episode of
      aseptic meningitis during combined CSA and EA.

PMID- 12803600
TI  - Fatal lipoid pneumonia due to bronco-aspiration of isoparaffin after ingestion of
      an organophosphate insecticide.
AB  - A 66-year-old-male patient with a history of depression voluntarily ingested
      around 400 ml of an insecticide composed of 5% methylparathion, 75% isoparaffin,
      8% etoxylated oleic acid, 4% 1,2,4-trimethylbenzene, 6% naphtha, 1% 1,3,5-
      trimethylbenzene, 0.4% propylbenzene and 0.3% xylene. The patient was conscious
      and alert at admission. Gastric lavage was performed and activated charcoal
      administered. There were no clinical symptoms of organophospate ingestion despite
      reduced concentrations of erythrocyte and plasma cholinesterase. Chest X-ray
      showed pulmonary infiltrate compatible with bronco-aspiration. The patient
      evolved to respiratory failure refractory to treatment and died from multiorganic
      failure 23 days after ingesting the insecticide. The pathological findings
      included a pulmonary fibrosis in the alveolar spaces which caused enlargement of
      the intra-alveolar septa. Abundant lipin-laden macrophages were observed within
      the alveolar spaces. We review the most relevant aspects of cases of fatal lipoid
      pneumonia and point out that on occasion severe or fatal intoxication is due to
      the substances accompanying the active ingredients.

PMID- 12803601
TI  - The possible neuroprotective effect of laudanosine, an atracurium and
      cisatracurium metabolite.

PMID- 12803603
TI  - Paraplegia in association with spinal/epidural anaesthesia caused by unrecognised
      vertebral metastasis.

PMID- 12803604
TI  - Anesthesiologist's role in bowel relaxation for artificial bladder construction.

PMID- 12803607
TI  - Structural requirements for the perception of ambient temperature signals in
      homeothermic heat production of skunk cabbage (Symlocarpus foetidus).
AB  - The spadix of skunk cabbage, Symplocarpus foetidus, is capable of maintaining an
      internal temperature of around 20 degrees C even when the ambient temperature
      drops to around 0 degrees C. To determine the crucial structure that is required
      for detection of ambient temperature signals, detailed measurements of the
      temperatures of the spadix were made under field conditions. The spadix
      temperature was well regulated even when the spathe or the leaf of the plant was
      removed. Furthermore, maintenance of the temperature of the central stalk at
      either 10 or 20 degrees C had no effect on the thermoregulation when the ambient
      temperature increased from 10 to 25 degrees C or decreased from 20 to 8 degrees
      C. Therefore, it seemed that the heat production in the spadix required neither
      the spathe, the leaf, nor the central stalk for perception of the external
      temperature signals. Finally, analysis of sugar composition in xylem exudates
      showed that the concentrations of sucrose, glucose, and fructose, all of which
      are potential energy sources of thermogenesis, did not change significantly at
      different ambient temperatures. It is concluded that the spadix is a unique organ
      in which the perception of ambient temperature signals and heat production occurs
      in S. foetidus.

PMID- 12803608
TI  - Root structure and cellular chloride, sodium and potassium distribution in
      salinized grapevines.
AB  - X-ray microanalysis was used to study the patterns of K+, Na+ and Cl-
      accumulation in salinized (25 mm NaCl) and non-salinized grapevine (Vitis) roots.
      The aim was to determine whether NaCl affects patterns of Cl- accumulation
      differentially in the roots of a Cl--excluding genotype and a non-excluding
      genotype. Two regions of fibrous roots were analysed: (1) a region 2-3 mm
      basipetal to the root tip; and (2) a region of the root 10-12 mm basipetal to the
      root tip where the outermost layer is the hypodermis. The ion contents of the
      hypodermis, cortex, endodermis and pericycle vacuoles were analysed. Data were
      also collected from the cytoplasm of the endodermal and pericycle cells. The
      analyses showed that the ion profiles of the hypodermis and the endodermis were
      significantly different from those of the cortex and pericycle. The hypodermis
      and endodermis had higher K+ and lower Na+ and Cl- than surrounding cells. Some
      changes due to salinity such as increased K+ concentrations in the hypodermis
      were also noted. Chloride concentrations did not differ between the genotypes in
      the hypodermis, across the cortex or in the endodermis, but were higher in the
      pericycle of the excluder in comparison with the non-excluding genotype. However,
      K+/Na+ ratios of the cortex and endodermis were higher in the excluder. The
      pericycle cells exhibited the greatest ability to sequester Na+ and Cl- in
      vacuoles. Overall the data show cell-type-specific ion accumulation patterns and
      small but significant differences were found between genotypes. The possibility
      that these accumulation patterns arise from differences in uptake properties of
      cell types and/or result from the spatial distribution of the cell types along
      the competing symplastic and apoplastic ion transport pathways across the root is
      discussed.

PMID- 12803609
TI  - On the progressive enrichment of the oxygen isotopic composition of water along a
      leaf.
AB  - A model has been derived for the enrichment of heavy isotopes of water in leaves,
      including progressive enrichment along the leaf. In the model, lighter water is
      preferentially transpired leaving heavier water to diffuse back into the xylem
      and be carried further along the leaf. For this pattern to be pronounced, the
      ratio of advection to diffusion (Peclet number) has to be large in the
      longitudinal direction, and small in the radial direction. The progressive
      enrichment along the xylem is less than that occurring at the sites of
      evaporation in the mesophyll, depending on the isolation afforded by the radial
      Peclet number. There is an upper bound on enrichment, and effects of ground
      tissue associated with major veins are included. When transpiration rate is
      spatially nonuniform, averaging of enrichment occurs more naturally with
      transpiration weighting than with area-based weighting. This gives zero average
      enrichment of transpired water, the modified Craig-Gordon equation for average
      enrichment at the sites of evaporation and the Farquhar and Lloyd (In Stable
      Isotopes and Plant Carbon-Water Relations, pp. 47-70. Academic Press, New York,
      USA, 1993) prediction for mesophyll water. Earlier results on the isotopic
      composition of evolved oxygen and of retro-diffused carbon dioxide are preserved
      if these processes vary in parallel with transpiration rate. Parallel variation
      should be indicated approximately by uniform carbon isotope discrimination across
      the leaf.

PMID- 12803610
TI  - Alterations in Cd-induced gene expression under nitrogen deficiency in Hordeum
      vulgare.
AB  - The inter-relation between nitrogen availability and cadmium toxicity was studied
      in roots of barley seedlings with emphasis on the analysis of expression of 10
      selected genes relevant for growth in the presence of toxic Cd concentrations.
      The response to Cd exposure differed quantitatively or qualitatively for the 10
      genes in dependence of the N supply. Transcripts of glutathione synthase,
      glutathione reductase, glutathione peroxidase and dehydroascorbate reductase were
      measured as parameters involved in antioxidant defence, metallothionein,
      phosphoenolpyruvate carboxylase and phytochelatin synthase (PCS) were analysed as
      genes related to heavy metal binding, and vacuolar ATPase subunits VHA-E and VHA
      c and a NRAMP-transporter as genes being implicated in Cd transport.
      Reprogramming of the Cd response was most obvious for PCS and NRAMP whose
      transcript levels were unaltered and down-regulated, respectively, in the
      presence of Cd at adequate N, but strongly up-regulated upon Cd exposure under
      conditions of nitrogen deficiency. Different responses to Cd at varying N supply
      were also seen for the antioxidant genes. The results on gene expression are
      discussed in context with the changes in biochemical parameters, and underline
      the importance of evaluating the general growth conditions of a plant when
      discussing its specific response to a stressor such as Cd. The sequence of the
      nramp cDNA was filed at the EMBL/GenBank/DDBJ Databases under the accession
      number AJ514946.

PMID- 12803611
TI  - Is there an optimal root architecture for nitrate capture in leaching
      environments?
AB  - Little is known about root architectural attributes that aid the capture of
      nitrate from coarse-textured soil profiles of high leaching potential. In this
      study, a range of root architectures from the herringbone to the dichotomous
      structure were simulated, and their capacity to take up nitrate leaching through
      a sandy profile was recorded. All root systems had equal total volume at each
      point in time, and so were considered cost equivalent. These simulations showed
      that the root architecture likely to maximize nitrate capture from sandy soils
      (under the Mediterranean rainfall pattern experienced in Western Australia) is
      one that quickly produces a high density of roots in the top-soil early in the
      season, thereby reducing total nitrate leached with opening season rains, but
      also has vigorous taproot growth, enabling access to deep-stored water and
      leached nitrate later in the season. This is the first published, spatially
      explicit attempt to assess the ability of different root architectures equivalent
      in cost, to capture nitrate from a spatially and temporally heterogeneous soil
      environment.

PMID- 12803612
TI  - Up-regulation of the leaf mitochondrial and peroxisomal antioxidative systems in
      response to salt-induced oxidative stress in the wild salt-tolerant tomato
      species Lycopersicon pennellii.
AB  - The response of the antioxidative systems of leaf cell mitochondria and
      peroxisomes of the cultivated tomato Lycopersicon esculentum (Lem) and its wild
      salt-tolerant related species Lycopersicon pennellii (Lpa) to NaCl 100 mM stress
      was investigated. Salt-dependent oxidative stress was evident in Lem mitochondria
      as indicated by their raised levels of lipid peroxidation and H2O2 content
      whereas their reduced ascorbate and reduced glutathione contents decreased.
      Concomitantly, SOD activity decreased whereas APX and GPX activities remained at
      control level. In contrast, the mitochondria of salt-treated Lpa did not exhibit
      salt-induced oxidative stress. In their case salinity induced an increase in the
      activities of superoxide dismutase (SOD), ascorbate peroxidase (APX),
      monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and
      glutathione-dependent peroxidase (GPX). Lpa peroxisomes exhibited increased SOD,
      APX, MDHAR and catalase activity and their lipid peroxidation and H2O2 levels
      were not affected by the salt treatment. The activities of all these enzymes
      remained at control level in peroxisomes of salt-treated Lem plants. The salt
      induced increase in the antioxidant enzyme activities in the Lpa plants conferred
      cross-tolerance towards enhanced mitochondrial and peroxisomal reactive oxygen
      species production imposed by salicylhydroxamic acid (SHAM) and 3-amino-1,2,4
      triazole (3-AT), respectively.

PMID- 12803613
TI  - Increases of chlorophyll a/b ratios during acclimation of tropical woody
      seedlings to nitrogen limitation and high light.
AB  - According to the theory of optimal nitrogen partitioning within a leaf, the
      chlorophyll (Chl) a/b ratio is expected to increase when leaf N content
      decreases. Here, we report the first empirical support for this prediction. The
      Chl a/b ratio increased while Chl content decreased in response to N limitation
      in photosynthetic cotyledons and leaves of seedlings of four tropical woody
      species in the Bignoniaceae. The responses of all four species were in the same
      direction, but differed in magnitude. For Tabebuia rosea, the species that
      exhibited the greatest increase in Chl a/b ratios (up to values of 5.9), detailed
      photosynthetic characteristics were also examined. Light and N availability were
      positively correlated with the light- and CO2-saturated photosynthetic O2
      evolution rate, as well as with leaf carboxylation capacity (Vcmax) and electron
      transport rate (Vj). Severe N limitation and high light did not cause chronic
      photo-inhibition (i.e. no change in quantum yield or in dark-acclimated Fv/Fm).
      The observed change in the ratio of Vcmax to leaf N in response to N availability
      was consistent with likely functional reasons for change in the Chl a/b ratio.
      Adjustment of the Chl a/b ratio was apparently an integral feature of acclimation
      to high light conditions and low N availability.

PMID- 12803614
TI  - Role of abscisic acid in cadmium tolerance of rice (Oryza sativa L.) seedlings.
AB  - Changes in abscisic acid (ABA) contents in Cd-treated rice (Oryza sativa L.)
      seedlings of two cultivars were investigated. On treatment with CdCl2, the ABA
      content rapidly increased in the leaves and roots of Cd-tolerant cultivar (cv.
      Tainung 67, TNG67) but not in the Cd-sensitive cultivar (cv. Taichung Native 1,
      TN1). The reduction of transpiration rate of TN1 caused by Cd was less than that
      of TNG67. Exogenous application of ABA reduced transpiration rate, decreased Cd
      content, and enhanced Cd tolerance of TN1 seedlings. Exogenous application of the
      ABA biosynthesis inhibitor, fluridone, reduced ABA accumulation, increased
      transpiration rate and Cd content, and decreased Cd tolerance of TNG67 seedlings.
      Fluridone effect on Cd toxicity of TNG67 seedlings was reversed by the
      application of ABA. The roles of endogenous ABA in Cd tolerance of rice seedlings
      are discussed and suggested.

PMID- 12803615
TI  - Responses of selected birch (Betula pendula Roth) clones to ozone change over
      time.
AB  - A long-term free air ozone fumigation experiment was conducted to study changes
      in physiological ozone responses during tree ontogeny and exposure time in ozone
      sensitive and tolerant clones of European white birch (Betula pendula Roth),
      originated from south and central Finland. The trees were grown in soil in
      natural microclimatic conditions under ambient ozone (control) and 1.4-1.7 x
      ambient (elevated) ozone from May 1996 to October 2001, and were measured for
      stem and foliage growth, net photosynthesis, stomatal conductance, stomatal
      density, visible injuries, foliar starch content and bud formation. After 6 years
      of exposure, the magnitude of ozone-induced growth reductions in the sensitive
      clone was 12-48% (significant difference), levels similar or greater than those
      reported earlier for 2- and 3-year-old saplings undergoing shorter exposures. In
      the tolerant clone, growth of these larger trees was reduced by 1-38%
      (significant difference in stem volume), although the saplings had previously
      been unaffected. In both clones, ozone stress led to significantly reduced leaf
      level net photosynthesis but significantly increased stomatal conductance rates
      during the late summer, resulting in a lower carbon gain for bud formation and
      the onset of visible foliar injuries. Increasing ozone sensitivity with duration
      of exposure was explained by a change in growth form (relatively reduced foliage
      mass), a lower photosynthesis to stomatal conductance ratio during the late
      summer, and deleterious carry-over effects arising from the reduced number of
      over-wintering buds.

PMID- 12803616
TI  - An apoplastic mechanism for short-term effects of rare earth elements at lower
      concentrations.
AB  - The short-term effects of rare earth elements on pollen germination and tube
      growth were tested. Concentrations of 2.5 approximately 20 micro m
      lanthanum(La3+) or cerium (Ce3+)increased pollen germination and pollen tube
      growth, whereas concentrations higher than 40 micro m La3+ and Ce3+ inhibited
      this process. The most effective concentration of La3+ needed for promotion
      shifted from 10 to 40 micro m, depending on the Ca2+ concentration in the medium.
      Calmodulin (CaM) antagonist W7-agarose and anti-CaM antibody depressed La3+
      promoted pollen germination and tube growth in a dose-dependent manner. La3+-CaM
      complexes (La3+-CaM) increased pollen germination and tube growth more than CaM
      or La3+ alone. Pertussis toxin (PTX) inhibited La3+-promoted pollen germination
      and tube growth. Cholera toxin (CTX) partially recovered the inhibition of the
      above La3+-promoted process by the anti-CaM antibody. Concentrations of 10-7
      approximately 10-9 m La3+-CaM increased GTPase activity inside plasma membrane
      vesicles of the pollen tube, but apo-CaM or La3+ alone had no positive effects.
      The results suggest that apoplastic CaM may be involved in the promotion effects
      of lower concentrations of La3+ on pollen germination and tube growth, and the
      heterotrimeric G-protein on the plasma membrane may transduce La3+-activated CaM
      signalling. The present studies provide an apoplastic mechanism for short-term
      effects of rare earth elements at lower concentrations in the pollen system.

PMID- 12803617
TI  - Rapid microalgal metabolism of selenate to volatile dimethylselenide.
AB  - An axenically cultured isolate of single-celled freshwater microalgae (Chlorella
      sp.) metabolized toxic selenate to volatile dimethylselenide at exceptionally
      high rates when transferred from mineral-nutrient solution to water for 24 h. The
      Se-volatilization rates were orders of magnitude higher than those similarly
      measured for wetland macroalgae and higher plants. Ninety percent of 20 micro m
      selenate supplied to the microalgae incubated without nutrients was removed
      through accumulation and volatilization. Additions of 1 mm sulphate but not
      nitrate, inhibited Se accumulation and volatilization so that only 1.8% of the
      supplied selenate was removed. The microalgae cultured in nutrient solution
      without sulphate showed increased 35S-sulphate-transporter activity. Selenium K
      edge X-ray absorption spectroscopy of selenate-treated microalgae cultured with
      or without mineral nutrients, showed that 87% of the selenate accumulated during
      24 h was reductively metabolized to intermediate organic compounds such as
      selenomethionine and selenocystine. This is in complete contrast to higher plants
      that show very limited reduction of selenate. It appears that high rates of Se
      accumulation and volatilization by the sulphate-deprived microalgae resulted from
      reduced competition with chemically analogous sulphate ions for selenate uptake
      via up-regulated sulphate/selenate transporters and rapid reductive metabolism of
      selenate. Hyper-volatilization of selenate by microalgal cells may provide a
      novel detoxification response.

PMID- 12803618
TI  - Differential expression of three members of the AMT1 gene family encoding
      putative high-affinity NH4+ transporters in roots of Oryza sativa subspecies
      indica.
AB  - In order to investigate the molecular basis of high-affinity ammonium absorption
      by roots of rice plants (Oryza sativa subspecies indica) the expression patterns
      of three members of the AMT1 family of genes in rice seedling roots in response
      to altered nitrogen provision and diurnal changes in irradiance were examined.
      The 13NH4+ influx and transcript levels of OsAMT1.1 in roots decreased several
      fold within 48 h when plants acclimated to 10 micro m external NH4+ for 3 weeks
      were transferred to 10 mm NH4+. Likewise when plants acclimated in 10 mm NH4+
      were transferred to 10 micro m NH4+, there was an equally rapid up-regulation of
      OsAMT1.1 and 13NH4+ influx in the roots. Changes in transcript abundance of
      OsAMT1.2 following these treatments were approximately 50% less than in OsAMT1.1,
      and changes of OsAMT1.3 expression were even less. By contrast, in response to
      the diurnal changes of irradiance, root transcript abundance of OsAMT1.3 and
      15NH4+ influx increased approximately three-fold late in the photoperiod, whereas
      OsAMT1.1 and OsAMT1.2 exhibited only modest changes. The present results suggest
      that high-affinity NH4+ influx is differentially regulated at the transcriptional
      level through the expression of three members of the OsAMT1 family of genes in
      roots of rice seedlings in response to changes of N status and daily irradiance.
      In general, these findings are in agreement with earlier observations in
      Arabidopsis and tomato.

PMID- 12803619
TI  - Three pathogen-inducible genes encoding lipid transfer protein from pepper are
      differentially activated by pathogens, abiotic, and environmental stresses.
AB  - The three cDNA clones, CALTPI, CALTPII, and CALTPIII, corresponding to pepper
      lipid transfer protein (LTP) genes were isolated from a pepper (Capsicum annuum)
      cDNA library from hypersensitive response (HR) lesions of leaves infected with
      Xanthomonas campestris pv. vesicatoria. The CALTP genes are well conserved in
      their coding region with 57-72% identity at the amino acid level, but display 72
      83% identity at the nucleotide sequence level. The transcripts of the three CALTP
      genes differentially accumulated in pepper leaf, stem, and fruit tissues infected
      by X. campestris pv. vesicatoria, Phytophthora capsici and Colletotrichum
      gloeosporioides. The CALTP genes were also strongly induced in the systemic,
      upper leaves after immunization on lower leaves by either pathogenic or non
      pathogenic bacteria. In situ hybridization results showed that the CALTPI mRNA
      was localized in phloem cells of vascular tissues in pepper leaf, stem and fruit
      tissues after pathogen infection. CALTPI and CALTPIII genes were predominantly
      expressed in various pepper tissues infected by pathogens, while infection by P.
      capsici and C. gloeosporioides did not induce the transcription of the CALTPII
      gene. Ethylene, methyl jasmonate and abscisic acid induced CALTPI and III gene
      expression in pepper leaves. Drought, high salinity, low temperature and wounding
      stresses also induced the expression of the CALTPI and CALTPIII genes in a
      similar manner. In contrast, only high salinity induced the CALTPII expression
      that was not generally affected by abiotic and other environmental stimuli. When
      compared with each other and with LTPs from other plants, CALTPI is more
      distantly related than CALTPII and CALTPIII sequences, indicating that the three
      pepper CALTP genes represent two different classes. These results thus show that
      CALTPI and CALTPIII genes, although different in sequence structure, are
      transcriptionally activated in pepper tissues by pathogen infection as well as
      abiotic and environmental stresses.

PMID- 12803620
TI  - Cross-talk between calcium and reactive oxygen species originated from NADPH
      oxidase in abscisic acid-induced antioxidant defence in leaves of maize
      seedlings.
AB  - The signal interactions between calcium (Ca2+) and reactive oxygen species (ROS)
      originated from plasma membrane NADPH oxidase in abscisic acid (ABA)-induced
      antioxidant defence were investigated in leaves of maize (Zea mays L.) seedlings.
      Treatment with ABA led to significant increases in the activity of plasma
      membrane NADPH oxidase, the production of leaf O2-, and the activities of several
      antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate
      peroxidase (APX) and glutathione reductase (GR). However, such increases were
      blocked by the pretreatment with Ca2+ chelator EGTA or Ca2+ channel blockers La3+
      and verapamil, and NADPH oxidase inhibitors such as diphenylene iodonium (DPI),
      imidazole and pyridine. Treatment with Ca2+ also significantly induced the
      increases in NADPH oxidase activity, O2- production and the activities of
      antioxidant enzymes, and the increases were arrested by pretreatment with the
      NADPH oxidase inhibitors. Treatment with oxidative stress induced by paraquat,
      which generates O2-, led to the induction of antioxidant defence enzymes, and the
      up-regulation was suppressed by the pretreatment of Ca2+ chelator and Ca2+
      channel blockers. Our data suggest that a cross-talk between Ca2+ and ROS
      originated from plasma membrane-bound NADPH oxidase is involved in the ABA signal
      transduction pathway leading to the induction of antioxidant enzyme activity, and
      Ca2+ functions upstream as well as downstream of ROS production in the signal
      transduction event in plants.

PMID- 12803621
TI  - Leaf-level phenotypic variability and plasticity of invasive Rhododendron
      ponticum and non-invasive Ilex aquifolium co-occurring at two contrasting
      European sites.
AB  - To understand the role of leaf-level plasticity and variability in species
      invasiveness, foliar characteristics were studied in relation to seasonal average
      integrated quantum flux density (Qint) in the understorey evergreen species
      Rhododendron ponticum and Ilex aquifolium at two sites. A native relict
      population of R. ponticum was sampled in southern Spain (Mediterranean climate),
      while an invasive alien population was investigated in Belgium (temperate
      maritime climate). Ilex aquifolium was native at both sites. Both species
      exhibited a significant plastic response to Qint in leaf dry mass per unit area,
      thickness, photosynthetic potentials, and chlorophyll contents at the two sites.
      However, R. ponticum exhibited a higher photosynthetic nitrogen use efficiency
      and larger investment of nitrogen in chlorophyll than I. aquifolium. Since leaf
      nitrogen (N) contents per unit dry mass were lower in R. ponticum, this species
      formed a larger foliar area with equal photosynthetic potential and light
      harvesting efficiency compared with I. aquifolium. The foliage of R. ponticum was
      mechanically more resistant with larger density in the Belgian site than in the
      Spanish site. Mean leaf-level phenotypic plasticity was larger in the Belgian
      population of R. ponticum than in the Spanish population of this species and the
      two populations of I. aquifolium. We suggest that large fractional investments of
      foliar N in photosynthetic function coupled with a relatively large mean, leaf
      level phenotypic plasticity may provide the primary explanation for the invasive
      nature and superior performance of R. ponticum at the Belgian site. With
      alleviation of water limitations from Mediterranean to temperate maritime
      climates, the invasiveness of R. ponticum may also be enhanced by the increased
      foliage mechanical resistance observed in the alien populations.

PMID- 12803622
TI  - Contrasting strategies for UV-B screening in sub-Arctic dwarf shrubs.
AB  - The content and distribution of UV-absorbing phenolic compounds was investigated
      in leaves of three species of Vaccinium co-existing at a site in north Sweden.
      Vaccinium myrtillus L., Vaccinium vitis-idaea L., and Vaccinium uliginosum L.
      exhibit markedly different strategies, in terms of localization and content of
      leaf phenolics and in their responses to UV-B enhancement. Plants were exposed to
      either ambient radiation or to enhancement of UV-B corresponding to 15% (clear
      sky) depletion of stratospheric ozone for approximately 10 years prior to
      commencement of this study. Vaccinium myrtillus contained the highest
      concentration of methanol-extractable UV-B-absorbing compounds, which was
      elevated in plants exposed to enhanced UV-B. Fluorescence and confocal laser
      scanning microscopy showed that these compounds were distributed throughout the
      leaf, and were particularly concentrated in chlorophyll-containing cells. In V.
      vitis-idaea, most phenolic compounds were cell wall-bound and concentrated in the
      walls of the epidermis; this pool increased in response to UV-B enhancement. It
      is suggested that these two plants represent extreme forms of two divergent
      strategies for UV-B screening, the different responses possibly being related to
      leaf longevity in the two species. The response of V. uliginosum was intermediate
      between the other two, with high concentrations of cell wall-bound phenolics in
      the epidermis but with this pool decreasing, and the methanol-soluble pool
      tending to increase, after exposure to enhanced UV-B. One explanation for this
      response is that this plant is deciduous, like V. myrtillus, but has leaves that
      are structurally similar to those of V. vitis-idaea.

PMID- 12803623
TI  - Cell-specific measurement of cytosolic glutathione in poplar leaves.
AB  - The level of glutathione (GSH) in plants is important in defence reactions
      against biotic and abiotic stresses and can place considerable demand of the
      sulphur assimilation pathway. Enzymes involved in sulphur assimilation and GSH
      metabolism are not evenly distributed between different subcellular compartments
      or between different cell types in leaves or roots; however, there is little
      information on the effect that such asymmetries have on the actual GSH
      concentration in each compartment or cell type. In the present study in situ
      labelling with monochlorobimane (MCB) in combination with confocal laser scanning
      microscopy was used to quantify GSH in each of the main cell types of poplar
      leaves from fluorescence of the GSB conjugate formed. Comparison of results from
      the in situ approach with total GSH levels measured in vitro by high-performance
      liquid chromatography suggested that only the cytosolic GSH pool was labelled
      using this approach. This suggests that an appropriate GST was not present within
      the chloroplasts to catalyse the conjugation reaction and that chloroplastic GSH
      does not rapidly exchange with the cytoplasmic pool under the conditions of the
      assay. Cytosolic GSH levels were between 0.2 and 0.3 mm for both photosynthetic
      and non-photosynthetic (epidermal) cell types in wild-type poplar leaves.
      Cytosolic levels increased by around two-fold in transgenic poplars over
      expressing bacterial gamma-glutamylsynthetase (gamma-ECS) in the cytosol of all
      cell types, but there was no concomitant increase in the chloroplastic GSH pool.

PMID- 12803624
TI  - Microsatellite variation within and among North American lineages of Phragmites
      australis.
AB  - Over the past century, the spread of the common reed (Phragmites australis) has
      had a dramatic impact on wetland communities across North America. Although
      native populations of Phragmites persist, introduced invasive populations have
      dominated many sites and it is not clear if the two types can interbreed. This
      study compares patterns of differentiation in 10 microsatellite loci among North
      American and European Phragmites individuals with results obtained from
      sequencing of noncoding chloroplast DNA. Three population lineages (native,
      introduced and Gulf Coast) were previously identified in North America from
      chloroplast DNA and similar structuring was found in the nuclear genome. Each
      lineage was distinguished by unique alleles and allele combinations and the
      introduced lineage was closely related to its hypothesized source population in
      Europe. Size homoplasy and diagnostic base substitutions distinguishing lineages
      were evident at several loci, further emphasizing that native, introduced and
      Gulf Coast North American Phragmites lineages are genetically distinct. Gene flow
      between lineages was low and invasive introduced populations do not represent a
      hybrid population type.

PMID- 12803625
TI  - Population genetics of the endangered Knysna seahorse, Hippocampus capensis.
AB  - The evolutionary history of the endangered Knysna seahorse, Hippocampus capensis,
      and the extent of gene flow among its three known populations, were investigated
      using 138 mitochondrial DNA control region sequences. Similarly high levels of
      genetic diversity were found in two of the populations (Knysna and Keurbooms
      Estuaries), whereas diversity in the third population (Swartvlei Estuary) was
      lower. Although most haplotypes are shared between at least two populations,
      based on the haplotype frequency distributions the three assemblages constitute
      distinct management units. The extant population structure of H. capensis
      suggests that the Knysna seahorse originated in the large Knysna Estuary. The
      presence of seahorses in the two smaller estuaries is either the result of a
      vicariance event at the beginning of the present interglacial period,
      colonization of the estuaries via the sea, or a combination of the two.

PMID- 12803626
TI  - Parental tracking in the postfire wood decay ascomycete Daldinia loculata using
      highly variable nuclear gene loci.
AB  - The origin of the male and female gametes involved in fertilization events within
      a local population of the postfire wood decay ascomycete Daldinia loculata was
      investigated by genotyping the mycelia growing in the wood and the sexual
      ascospores, using three highly variable nuclear gene loci. The study was
      conducted in a geographically isolated burned forest site in southern Sweden. An
      intensive sampling was performed by collecting stromata containing ascospores and
      wood samples containing mycelia. In total, from 32 mapped burned birches,
      cultures of 22 haploid genets from decayed wood and six ascospores from each of
      19 stromata were isolated and analysed. In 80% of the investigated burned
      branches, only one genet was found. From the analysis of the ascospore genotypes,
      we detected 30 fertilization events and 60% of them were the result of mating
      between conidia (clonal propagules) acting as male gametes and the genets in the
      branches representing the female gametes. The male parents producing the conidia
      were detected within the same local population as the female parents in 27% of
      the fertilization events and originated either from the same branch or from
      different trees located at 0.5-36 m away from the female parents. In 33% of the
      fertilization events, conidia originated from three male parents that were not
      found within the local population sampled. These parents could be anywhere inside
      or outside the sampled area. For the remaining fertilization events, we could not
      rule out the ascospores or the conidia as fertilizing propagules. No strong
      evidence for fertilization by recombinant propagules (ascospores) was detected in
      this study. The pyrophilous insect species associated with conidia of D. loculata
      are suggested to be essential vectors for the realization of the sexual cycle of
      this fungal species. By feeding on the conidia and flying between nearby trees
      inhabiting wood decay mycelia, these insects allow the transfer of conidia and
      therefore the opposite mating types to meet within a localized burned forest
      site.

PMID- 12803627
TI  - Fine-scale genetic structure of two carabid species with contrasted levels of
      habitat specialization.
AB  - Using microsatellite markers, we compared the genetic structure of populations of
      two carabid species, one described as a generalist (commonly found in forest and
      in open habitats) and the other known as a forest specialist. Both species were
      sampled in the same forest plots, which were separated from each other by either
      open or forested areas. At the local scale considered (13.6 km separating the
      most distant plots), genetic differentiation was substantial for both species
      studied, but populations of the forest specialist Carabus punctatoauratus
      appeared to be more spatially structured than those of C. nemoralis. Isolation by
      distance analyses showed that nonforested areas are partial barriers to gene flow
      for both species studied, although more clearly for the forest specialist.
      Between and within forests, dispersal capacity of the generalist C. nemoralis was
      shown to be higher than that of the specialist C. punctatoauratus.

PMID- 12803628
TI  - Population genetics of an invasive species, Heracleum mantegazzianum:
      implications for the role of life history, demographics and independent
      introductions.
AB  - The population genetic structure of an invasive, nonindigenous riparian weed
      (Heracleum mantegazzianum) in the northeast of England was investigated using
      microsatellite DNA markers. Data were used to assess the size and frequency of
      introductions into three catchments and the subsequent spread. We sampled 13
      populations, including a remote population (Perivale, London) for comparison.
      Five loci were screened and considerable variation was found. Results revealed
      greater overall variation between populations from different catchments than
      those in the same catchment, and suggested the generation of population structure
      in the relatively short time since the initial introduction. Between-catchment
      variation may reflect population structure generated by local founders as the
      species spread and may indicate a large initial founder population at the time of
      the introduction into Britain, or multiple introductions. Within-catchment
      variation was consistent with expectations based on the water-borne dispersal of
      seeds in this species, and the relatively small dispersal range of likely
      pollinators. Independent introductions stand out in some cases as exceptions to
      the general pattern. Taken together the results are consistent with a relatively
      large initial founder population, and the subsequent spread of the species in
      local founder populations, followed by some level of inbreeding within local
      populations and novel introductions in some localities.

PMID- 12803629
TI  - Effects of Wolbachia on mtDNA variation in two fire ant species.
AB  - Wolbachia are endosymbiotic bacteria that infect arthropods. As they are
      maternally transmitted, the spread of Wolbachia variants within host populations
      may affect host mtDNA evolution. We sequenced a portion of the mitochondrial
      cytochrome oxidase I gene from numerous individuals of two Wolbachia-infected
      fire ant species, Solenopsis invicta and S. richteri, to determine how these
      bacteria influence patterns of mtDNA variation. As predicted, there was a strong
      association between Wolbachia strain and host mtDNA lineage within and between
      these fire ant species. However, there was no consistent association between the
      presence of Wolbachia and a reduction in mtDNA diversity. Moreover, patterns of
      mtDNA variation within Wolbachia-infected populations did not differ consistently
      from neutral expectations, despite our prediction that strong positive selection
      acting on Wolbachia influences the evolutionary dynamics of other cytoplasmic
      genomes. Specifically, while values of Tajima's D consistently were less than
      zero for all six samples of fire ants harbouring Wolbachia, MacDonald-Kreitman
      tests suggested that the patterns of variation were different from those expected
      under neutrality in only two of the samples. We conclude that these neutrality
      tests do not unambiguously reveal a clear effect of Wolbachia infection on
      patterns of mtDNA variation and substitution in fire ants. Finally, consistent
      with an earlier study, our data revealed the presence of two divergent mtDNA
      haplotype lineages and Wolbachia strains within S. invicta. Recognition of these
      two lineages has important consequences for interpreting patterns of mtDNA
      evolution and genetic differentiation between conspecific social forms of this
      species.

PMID- 12803630
TI  - From connectivity to isolation: genetic consequences of population fragmentation
      in capercaillie across Europe.
AB  - The capercaillie inhabits a continuous range in large parts of the Palearctic
      boreal forest, but is patchily distributed in temperate Europe. An ongoing
      population decline, largely related to human land use changes, has been most
      pronounced in central and western Europe, where some local populations have
      become extinct. In this study, we document the genetic differentiation of
      capercaillie populations at different stages along a gradient of spatial
      structuring from high connectivity (continuous range in the boreal forest) to a
      metapopulation systems (Alps) and recent (central Europe) and historic (Pyrenees)
      isolation. Four hundred and sixty individuals from 14 sample sites were genotyped
      at 10 polymorphic microsatellite loci to assess genetic structure and variation
      of capercaillie populations across its European range. As expected,
      differentiation was least pronounced within the continuous range in the boreal
      forest. Within the metapopulation system of the Alps, differentiation was less
      than among the isolated populations of central Europe (Black Forest,
      Fichtelgebirge, Thuringia, Vosges). In the long-isolated population of the
      Pyrenees, and the recently isolated populations of central Europe, genetic
      diversity was significantly reduced compared with the Alps and boreal forest. Our
      results agree with the concept of a gradual increase in genetic differentiation
      from connectivity to isolation, and from recent to historic isolation.
      Anthropogenic habitat deterioration and fragmentation thus not only leads to
      range contractions and extinctions, but may also have significant genetic and
      evolutionary consequences for surviving populations. To maintain high levels of
      genetic variation in species in fragmented habitats, conservation should aim at
      securing connectivity between spatially distinct populations.

PMID- 12803631
TI  - The phylogeography of dusky dolphins (Lagenorhynchus obscurus): a critical
      examination of network methods and rooting procedures.
AB  - We investigated the phylogeography and evolutionary history of dusky dolphins
      (Lagenorhynchus obscurus) using DNA sequences of the full mitochondrial
      cytochrome b gene in 124 individuals from the putative stocks off Peru, Argentina
      and Southwest Africa. While genetic differentiation within oceans is surprisingly
      low, there is no evidence for recent female gene flow between Atlantic and
      Pacific waters. Highest genetic variability in terms of sequence divergence and
      number of haplotypes is found in the Atlantic. Our analyses also indicate that
      the eastern South Pacific dusky dolphins stock should be considered a separate
      management unit. Given the high level of mortality experienced by the Peruvian
      dusky dolphin in local fishery activities, these findings have important
      implications for an objective management of the species. Furthermore, we analysed
      our mitochondrial sequence data with several widely used network estimation and
      rooting methods. The resulting intraspecific gene genealogies and rooting
      inferences exhibited substantial differences, underlying the limitations of some
      algorithms. Given that scientific hypotheses and management decisions depend
      strongly on inferred tree or network topologies, there is a clear need for a
      systematic comparative analysis of available methods. Finally, the present study
      indicates that (i) the dusky and the Pacific white-sided dolphins are sister
      species and (ii) not only the Westwind Drift hypothesis but also other models of
      dispersion are compatible with the current geographical distribution of dusky
      dolphins.

PMID- 12803632
TI  - Bimodal run distribution in a northern population of sockeye salmon (Oncorhynchus
      nerka): life history and genetic analysis on a temporal scale.
AB  - Life history variation and genetic differentiation were analysed in sockeye
      salmon in Klukshu River, Yukon Canada over 7 years (1994-2000). Sockeye salmon
      return to the Klukshu River in two distinct runs, with a small 'early run' in
      June-August, and a larger 'late run' in August-September. A maximum likelihood
      test for clusters indicated that the return frequency distribution was bimodal in
      all the years analysed. Life history differences (fork length, sex ratio, age at
      maturity, fresh- and saltwater residency times) were found between the early and
      late runs; however, inconsistent patterns suggest that environmental effects
      outweigh, or strongly interact with, genetic effects for the life history
      characters evaluated. Analysis of variation at eight microsatellite loci showed
      that the early and late runs are genetically differentiated in all years examined
      (exact test). FST estimates between runs within years were significantly greater
      than zero (range: 0.018-0.041) for all years except one (0.004). The genetic
      variance explained by early vs. late runs (2.27%) was twice the variance among
      years (1.16%) based on analysis of molecular variance. Our neighbour-joining tree
      showed early and late runs generally clustering separately, indicating higher
      gene flow among the early or late run fish across years relative to between-run
      gene flow. Two years did not fit the general clustering pattern; although the
      early and late runs in 1995 and 2000 were genetically differentiated, they
      clustered separately from the rest of the groups. We cannot offer a definitive
      explanation for these anomalies; however, an analysis of possible cryptic
      population structure in early and late runs indicated that at least a few fish
      strayed between the runs in each year, and the highest rate of mixing was in 1995
      and 2000. Our data indicate that the runs are at least partially reproductively
      isolated as a result of temporal and/or spatial isolating mechanisms. Such
      reproductive isolation has important implications for conservation and management
      of the Klukshu sockeye salmon, and make them an evolutionarily interesting group
      because of parallels with incipient speciation.

PMID- 12803633
TI  - Landscape location affects genetic variation of Canada lynx (Lynx canadensis).
AB  - The effect of a population's location on the landscape on genetic variation has
      been of interest to population genetics for more than half a century. However,
      most studies do not consider broadscale biogeography when interpreting genetic
      data. In this study, we propose an operational definition of a peripheral
      population, and then explore whether peripheral populations of Canada lynx (Lynx
      canadensis) have less genetic variation than core populations at nine
      microsatellite loci. We show that peripheral populations of lynx have fewer mean
      numbers of alleles per population and lower expected heterozygosity. This is
      surprising, given the lynx's capacity to move long distances, but can be
      explained by the fact that peripheral populations often have smaller population
      sizes, limited opportunities for genetic exchange and may be disproportionately
      affected by ebbs and flows of species' geographical range.

PMID- 12803634
TI  - Post-ice age recolonization and differentiation of Fucus serratus L.
      (Phaeophyceae; Fucaceae) populations in Northern Europe.
AB  - The seaweed Fucus serratus is hypothesized to have evolved in the North Atlantic
      and present populations are thought to reflect recolonization from a southern
      refugium since the last glacial maximum 18 000-20 000 years bp. We examined
      genetic structure across several spatial scales by analysing seven microsatellite
      loci in populations collected from 21 localities throughout the species' range.
      Spatial auto-correlation analysis of seven microsatellite loci revealed no
      evidence for spatial clustering of alleles on a scale of 100 m despite limited
      gamete dispersal in F. serratus of approximately 2 m from parental individuals.
      Pairwise theta analysis suggested that the minimal panmictic unit for F. serratus
      was between 0.5 and 2 km. Isolation by distance was significant along some
      contiguous coastlines. Population differentiation was strong within the Skagerrak
      Kattegat-Baltic Seas (SKB) (global theta= 0.17) despite a short history of
      approximately 7500 years. A neighbour-joining tree based on Reynold's distances
      computed from the microsatellite data revealed a central assemblage of
      populations on the Brittany Peninsula surrounded by four well-supported clusters
      consisting of the SKB, the North Sea (Ireland, Helgoland), and two populations
      from the northern Spanish coast. Samples from Iceland and Nova Scotia were most
      closely aligned with northwest Sweden and Brittany, respectively. When sample
      sizes were standardized (N = 41), allelic diversity was twofold higher for
      Brittany populations than for populations to the north and threefold higher than
      southern populations. The Brittany region may be a refugium or a recolonized
      area, whereas the Spanish populations most likely reflect present-day edge
      populations that have undergone repeated bottlenecks as a consequence of
      thermally induced cycles of recolonization and extinction.

PMID- 12803635
TI  - Hybridization and Rorippa austriaca (Brassicaceae) invasion in Germany.
AB  - Introgressive hybridization between the invasive Rorippa austriaca and the native
      R. sylvestris in Germany has been studied using chloroplast DNA (trnL intron) and
      amplified fragment length polymorphism. Three hybrid zones between the invasive
      and native species were located in the Ruhr Valley (Mulheim) and at the River
      Main near Wurzburg (Randersacker, Winterhausen). In each hybrid zone
      hybridization was indicated by additivity of region-specific amplified fragment
      length polymorphism markers proving independent hybridization events. The hybrids
      were either morphologically intermediate (R. x armoracioides) or were close to R.
      sylvestris. The trnL intron of R. austriaca is characterized by a species
      specific deletion. This diagnostic chloroplast marker of R. austriaca was
      detected in three individuals of R. sylvestris providing evidence for
      introgression of the invasive chloroplast into the native species. Bidirectional
      introgression of R. austriaca markers into R. sylvestris and of R. sylvestris
      markers into R. austriaca was detected in the amplified fragment length
      polymorphism analysis. Some of the invasive R. austriaca populations showed high
      within-population variation. A possible association among introgression, within
      population variation and invasion success is discussed. The morphologically
      intermediate hybrid R. x armoracioides is currently spreading in northern
      Germany. It forms large populations without its parent species R. austriaca and
      R. sylvestris. It is concluded that hybridization between invasive R. austriaca
      and native R. sylvestris may lead to the evolution of a new invasive species R. x
      armoracioides.

PMID- 12803636
TI  - Wolbachia and genetic variability in the birdnest blowfly Protocalliphora sialia.
AB  - Wolbachia are widespread cytoplasmically inherited bacteria that induce various
      reproductive alterations in host arthropods, including cytoplasmic
      incompatibility (CI), an incompatibility between sperm and egg that typically
      results in embryonic death. CI has been invoked as a possible mechanism for
      reproductive isolation and speciation in arthropods, by restricting gene flow and
      promoting maintenance (and evolution) of genetic divergence between populations.
      Here we investigate patterns of Wolbachia infection and nuclear and mitochondrial
      differentiation in geographical populations of the birdnest blowfly
      Protocalliphora sialia. Blowflies in western North America are infected with two
      A-group Wolbachia, with some individuals singly and others doubly infected.
      Individuals in eastern North America mostly show single infections with a B-group
      Wolbachia. Populations in the Midwest are polymorphic for infections and show A-
      or B-group infection. There is a low level of mitochondrial divergence and
      perfect concordance of mitochondrial haplotype with infection type, suggesting
      that two Wolbachia-associated selective sweeps of the mitochondrion have occurred
      in this species. Amplified fragment length polymorphism analysis of nuclear
      genetic variation shows genetic differentiation between the eastern-Midwestern
      and western populations. Both Midwestern and eastern flies infected with A
      Wolbachia show eastern nuclear genetic profiles. Current results therefore
      suggest that Wolbachia has not acted as a major barrier to gene flow between
      western and eastern-Midwestern populations, although some genetic differentiation
      between A-Wolbachia infected and B-Wolbachia infected individuals in eastern
      Midwestern populations cannot be ruled out.

PMID- 12803637
TI  - Historical biogeography of the catfish genus Hypostomus (Siluriformes:
      Loricariidae), with implications on the diversification of Neotropical
      ichthyofauna.
AB  - Tropical South America possesses the largest ichthyofauna of any continental
      region. To test whether palaeohydrological changes may have been the causes of
      such diversification, the 'hydrogeological' hypothesis, the phylogenetic
      relationships of 51 representatives of the catfish genus Hypostomus
      (Siluriformes: Loricariidae) were inferred using mitochondrial D-loop haplotype
      sequences. Specimens were collected in all main tropical South American rivers
      systems east to the Andes. The major interrelationships found with the D-loop
      data were confirmed with a subset of 21 species using complete internal
      transcribed spacer (ITS) region sequences. The phylogenetic analysis indicate
      that the genus Hypostomus can be divided into four monophyletic clades. The
      historical biogeographical analysis of each of these clades allows the
      identification of seven major cladogenetic events. Using calibrated D-loop and
      ITS molecular clocks, date estimations were attributed to each of these
      cladogenetic events allowing a linkage between four of them with documented
      hydrogeological changes. Comparisons with published distribution patterns of
      unrelated fish groups indicate that several of the reconstructed and dated
      hydrogeological-cladogenetic events may have acted at a large scale on the
      diversification of Neotropical freshwater fish fauna during late Tertiary.

PMID- 12803640
TI  - The demographic history of the New Zealand short-tailed bat Mystacina tuberculata
      inferred from modified control region sequences.
AB  - Short-tailed bats Mystacina tuberculata were widespread throughout the forest
      that dominated prehuman New Zealand, but extensive deforestation has restricted
      them to scattered populations in forest fragments. In a previous study, the
      species' intraspecific phylogeny was investigated using multiple mitochondrial
      gene sequences. Six phylogroups were identified with estimated divergences of
      0.93-0.68 Ma. In the current study, the phylogeographical structure and
      demographic history of the phylogroups were investigated using control region
      sequences modified by removing homoplasic sites. Phylogeographical structure in
      the North Island was generally consistent with an isolation-by-distance dispersal
      model. Coalescent-based analyses (i.e. mismatch distributions, skyline plots,
      lineage dispersal analysis and nested clade analysis) indicated that the three
      phylogroups found in central and southern North Island expanded before the last
      glacial maximum, presumably during interstadials when Nothofagus forest was most
      extensive. Genetic structure within a central North Island hybrid zone was
      consistent with range expansion from separate refugia following reforestation
      after catastrophic volcanic eruptions. Phylogeographical structure in the South
      Island was consistent with southern populations originating during rapid
      southward range expansion from refugia in northern South Island following
      postglacial reforestation of the South Island 10-9 kya.

PMID- 12803638
TI  - The evolution of extreme shell shape variation in the land snail Ainohelix
      editha: a phylogeny and hybrid zone analysis.
AB  - Ainohelix editha from Hokkaido, Japan, exhibit great geographical variation in
      their shell morphology. In particular, A. editha in two quite separate locations,
      Shimamaki and Samani, are striking because they are extremely flat and have a
      sharp keel, whereas at adjacent sites the shells are globular or depressed
      globular. We used mitochondrial 16S rRNA and nuclear ITS-2 sequences to infer a
      phylogeny among 47 snails from 29 locations. Snails from the two keeled-flat
      populations clustered separately in the phylogeny, suggesting that this unusual
      shell form could have evolved independently. A morphological analysis of shells
      collected along a transect between keeled-flat and globular snail sites showed a
      cline for shell shape and the angle of the keel. Two different mtDNA lineages
      were found across the transect, with a cline for an ITS-2 single nucleotide
      polymorphism. Together, the results may suggest a lack of reproductive isolation
      between keeled-flat and globular snails, with possible introgression by
      hybridization.

PMID- 12803639
TI  - Genetic identification of two sibling species of Lutzomyia longipalpis (Diptera:
      Psychodidae) that produce distinct male sex pheromones in Sobral, Ceara State,
      Brazil.
AB  - Lutzomyia longipalpis, the main sandfly vector for New World visceral
      leishmaniasis is a complex of an as yet undefined number of sibling species. At
      present, there is no consensus on the status (single species vs. species complex)
      of Brazilian populations. We applied five microsatellite loci to test the
      hypothesis that L. longipalpis occurs as two sympatric cryptic species in Sobral,
      Ceara State, Brazil as predicted by male sex pheromone chemotypes described
      previously for field specimens from this site [S-9-methyl-germacrene-B (9MGB) and
      a cembrene compound]. Abdominal spot morphology corresponds with pheromone type
      at this locality (9MGB in '1 spot' males and cembrene in '2 spot' males).
      Genotype data from 190 wild-caught L. longipalpis specimens collected in October
      1999 and April 2001 were used to estimate genetic differentiation between the two
      sex pheromone populations and sampling dates. No significant (P > 0.05) genetic
      differences were found between the 1999 and 2001 9MGB samples (theta = 0.018; RST
      = -0.005), and genetic differentiation was low between the cembrene collections
      (theta = 0.037, P < 0.05; RST = -0.043, P > 0.05). By contrast, highly divergent
      allelic frequencies (largely at two microsatellite loci) corresponded to
      significant (P > 0.05) genetic differentiation (theta = 0.221; RST = 0.215) for
      all comparisons between samples with different pheromones. When pheromone samples
      were pooled across sample date, genetic differentiation was high (theta = 0.229;
      P < 0.001; Nem = 0.84). The allele frequency distribution at each of the five
      microsatellite loci was similar for males and females from the two collection
      years. Two of these loci showed highly divergent allele frequencies in the two
      sex pheromone populations. This was reflected in the highly significant genetic
      differentiation obtained from the male genotypes, between populations producing
      different pheromones (theta = 0.229-0.268; P < 0.0001 for the 2001 and theta =
      0.254-0.558; P < 0.0001 for the 1999 collections, respectively). Similar results
      were obtained when the females, assigned to a pheromone type, were included in
      the analysis. Both a Bayesian analysis of the data set and a population
      assignment test provided strong evidence for two distinct populations
      corresponding to pheromone type. Given its genotype, the probability of assigning
      a 9MGB male to the original 9MGB population was 100% once the two years'
      collections were pooled. For cembrene-producing '2 spot' males this probability
      although still high, was lower than for 9MGB males, at 86%. This microsatellite
      data together with previously reported reproductive isolation between the two
      Sobral populations confirm that premating barriers are important in speciation of
      L. longipalpis.

PMID- 12803641
TI  - Nuclear markers, mitochondrial DNA and male secondary sexual traits variation in
      a newt hybrid zone (Triturus vulgaris x T. montandoni).
AB  - The smooth and the Montandon's newts (Triturus vulgaris and T. montandoni) are
      genetically similar sister species with highly divergent male secondary sexual
      traits involved in complex courtship behaviour. Their parapatric ranges overlap
      at moderate elevations in the Carpathian Mountains where they hybridize readily.
      Here we present a detailed study of genetic and morphological variation in
      populations from the area of sympatry. Analysis of variation at seven nuclear
      markers, mtDNA and male sexual secondary traits was complemented with an
      ecological survey of breeding sites characteristics. Extensive hybridization was
      revealed with back-cross individuals similar to either parental species
      predominating among hybrids. The hybrid zone exhibited a mosaic pattern: the
      genetic composition of the populations was correlated only weakly with their
      geographical position. No association with habitat type was found. Departures
      from Hardy-Weinberg proportions, significant linkage disequilibria and bimodal
      distribution of genotypes suggest strongly that assortative mating is an
      important factor shaping the genetic composition of hybrid populations. The
      pattern of cytonuclear disequilibria did not indicate much asymmetry in
      interspecific matings. Changes in the frequency of nuclear markers were highly
      concordant, whereas mtDNA showed much wider bidirectional introgression with 14%
      excess of T. montandoni haplotype. We argue that the mosaic structure of the newt
      hybrid zone results mainly from stochastic processes related to extinction and
      recolonization. Microgeographical differences in mtDNA introgression are
      explained by historical range shifts. Since morphologically intermediate males
      were underrepresented when compared to hybrid males identified by genetic
      markers, sexual selection acting against the morphological intermediates is
      implied. We discuss the implications of these findings in the context of
      reinforcement of prezygotic isolation in newts.

PMID- 12803642
TI  - Determinants of intracolonial relatedness in Pogonomyrmex rugosus (Hymenoptera;
      Formicidae): mating frequency and brood raids.
AB  - The genus Pogonomyrmex is one of three ant genera with an effective mating
      frequency (me) > 2.0. We developed microsatellites to determine me for P. rugosus
      because mating frequency of P. rugosus was known only from observational data
      which do not allow an estimate of me. We genotyped 474 workers from 20 colonies
      for two microsatellite loci. Observed mating frequencies ranged from 3 to 12 and
      me for P. rugosus was 4.71. Observed patriline frequencies were significantly
      different from the expected patriline frequencies generated with a simulated data
      set under the assumption of equal patriline representation. The available mating
      frequency data and phylogenetic information of the genus Pogonomyrmex suggest
      that multiple mating is the ancestral state in the North American Pogonomyrmex
      sensu stricto. Established P. rugosus colonies raid and destroy smaller
      conspecific colonies. During these raids ant workers were observed carrying pupae
      and larvae from the raided colony into the nest of the raiding colony. However,
      it was not clear whether raided brood emerged in the raiding colony and were
      subsequently recruited into the work force (intraspecific slavery) or were used
      as food (predation). Our analyses indicate 6 of 14 field colonies contained
      foreign P. rugosus workers (43%). The range of the intracolonial frequency of
      foreign workers collected directly from the nest entrance was between 4 and 28%.

PMID- 12803643
TI  - Parentage assignment detects frequent and large-scale dispersal in water voles.
AB  - Estimating the rate and scale of dispersal is essential for predicting the
      dynamics of fragmented populations, yet empirical estimates are typically
      imprecise and often negatively biased. We maximized detection of dispersal events
      between small, subdivided populations of water voles (Arvicola terrestris) using
      a novel method that combined direct capture-mark-recapture with microsatellite
      genotyping to identify parents and offspring in different populations and hence
      infer dispersal. We validated the method using individuals known from trapping
      data to have dispersed between populations. Local populations were linked by high
      rates of juvenile dispersal but much lower levels of adult dispersal. In the
      spring breeding population, 19% of females and 33% of males had left their natal
      population of the previous year. The average interpopulation dispersal distance
      was 1.8 km (range 0.3-5.2 km). Overall, patterns of dispersal fitted a negative
      exponential function. Information from genotyping increased the estimated rate
      and scale of dispersal by three- and twofold, respectively, and hence represents
      a powerful tool to provide more realistic estimates of dispersal parameters.

PMID- 12803644
TI  - The role of environment in shaping the genetic diversity of the subalpine
      mosquito, Aedes rusticus (Diptera, Culicidae).
AB  - The relative involvement of larval dietary tolerance to the leaf-litter toxic
      polyphenols in shaping population genetic structure of the subalpine mosquito
      Aedes rusticus was examined. This was compared with other parameters such as
      geographical range, type of vegetation surrounding the breeding site, and
      occurrence of annual larvicidal treatments. Population genetic structure was
      analysed at 10 presumed neutral polymorphic isoenzyme loci. Toxicological
      comparisons involved standard bioassays performed on larvae fed on toxic
      decomposed leaf litter. Significant overall genetic differentiation was observed
      among the 22 studied populations and within the five defined geographical groups.
      Analysis of molecular variance revealed an absence of relation between genetic
      and environmental parameters, genetic variance being essentially found within
      populations. This suggested that the larval dietary tolerance to the toxic leaf
      litter and the other studied parameters poorly influence population genetic
      structure. The local adaptation of subalpine mosquito populations to the
      surrounding vegetation thus appears as a labile trait. Such a dynamic adaptation
      is also suggested by the correlation between geographical and toxicological
      distances and the correlation between dietary tolerance to the leaf-litter toxic
      polyphenols and annual larvicidal treatments.

PMID- 12803645
TI  - Latitudinal divergence of common frog (Rana temporaria) life history traits by
      natural selection: evidence from a comparison of molecular and quantitative
      genetic data.
AB  - The relative roles of natural selection and direct environmental induction, as
      well as of natural selection and genetic drift, in creating clinal latitudinal
      variation in quantitative traits have seldom been assessed in vertebrates. To
      address these issues, we compared molecular and quantitative genetic
      differentiation between six common frog (Rana temporaria) populations along an
      approximately 1600 km long latitudinal gradient across Scandinavia. The degree of
      population differentiation (QST approximately 0.81) in three heritable
      quantitative traits (age and size at metamorphosis, growth rate) exceeded that in
      eight (neutral) microsatellite loci (FST = 0.24). Isolation by distance was clear
      for both neutral markers and quantitative traits, but considerably stronger for
      one of the three quantitative traits than for neutral markers. QST estimates
      obtained using animals subjected to different rearing conditions (temperature and
      food treatments) revealed some environmental dependency in patterns of population
      divergence in quantitative traits, but in general, these effects were weak in
      comparison to overall patterns. Pairwise comparisons of FST and QST estimates
      across populations and treatments revealed that the degree of quantitative trait
      differentiation was not generally predictable from knowledge of that in molecular
      markers. In fact, both positive and negative correlations were observed depending
      on conditions where the quantitative genetic variability had been measured. All
      in all, the results suggest a very high degree of genetic subdivision both in
      neutral marker genes and genes coding quantitative traits across a relatively
      recently (< 9000 years) colonized environmental gradient. In particular, they
      give evidence for natural selection being the primary agent behind the observed
      latitudinal differentiation in quantitative traits.

PMID- 12803646
TI  - AFLP utility for population assignment studies: analytical investigation and
      empirical comparison with microsatellites.
AB  - Individual-based population assignment tests have thus far mainly relied on the
      use of microsatellite loci. However, the logistic difficulty of screening large
      numbers of loci required to reach sufficient statistical power hampers the
      usefulness of microsatellites in situations of weak population structuring.
      Amplified fragment length polymorphisms (AFLP) represents an alternative for
      overcoming this logistical issue as the technique allows the user to characterize
      a much larger number of loci with a comparable analytical effort. In this study,
      an assignment test based on maximum likelihood for dominant markers was used to
      investigate the potential usefulness of AFLP for population assignment. We also
      compared assignment success achieved with AFLP with that obtained using
      microsatellites in a case study of low population differentiation involving
      whitefish (Coregonus clupeaformis) sympatric ecotypes. The analytical
      investigation showed that the minimum number of AFLP loci required to reach an
      assignment success of 95% stood within values that are easily achievable in many
      situations. This also showed how assignment success varied according to the
      number of AFLP loci used, their absolute frequency and their frequency
      differential and sampling errors, as well as the number of putative source
      populations. The case study showed that given a comparable analytical effort in
      the laboratory, AFLP were much more efficient than the microsatellite loci in
      discriminating the source of an individual among putative populations. AFLP
      resulted in higher assignment success at all levels of stringency and the log
      likelihood differences between populations obtained with AFLP for each individual
      were much larger than those obtained with microsatellites. These results indicate
      that research involving individual-based population assignment methods should
      benefit importantly from the use of AFLP markers, especially in systems
      characterized by weak population structuring.

PMID- 12803647
TI  - Calibrating phylogenetic species formation in a threatened insect using DNA from
      historical specimens.
AB  - Museum specimens from the late 19th and early 20th centuries were surveyed for
      the single nucleotide polymorphism identified previously and used to diagnose
      populations of the federally threatened Northeastern Beach Tiger Beetle Cicindela
      d. dorsalis (Coleoptera: Carabidae). Widespread polymorphism was revealed
      throughout the historical range of this species, suggesting a relatively recent
      anthropogenic character fixation event associated with the extinction and
      fragmentation of populations. Implications for the phylogenetic species criterion
      and for the reintroduction of individuals to formerly occupied sites are
      discussed.

PMID- 12803648
TI  - A new approach to detecting mixed families.
AB  - There are several analyses in evolutionary ecology which assume that a family of
      offspring has come from only two parents. Here, we present a simple test for
      detecting when a batch involves two or more subfamilies. It is based on the fact
      that the mixing of families generates associations amongst unlinked marker loci.
      We also present simulations illustrating the power of our method for varying
      numbers of loci, alleles per locus and genotyped individuals.

PMID- 12803649
TI  - Population size estimation in Yellowstone wolves with error-prone noninvasive
      microsatellite genotypes.
AB  - Determining population sizes can be difficult, but is essential for conservation.
      By counting distinct microsatellite genotypes, DNA from noninvasive samples
      (hair, faeces) allows estimation of population size. Problems arise because
      genotypes from noninvasive samples are error-prone, but genotyping errors can be
      reduced by multiple polymerase chain reaction (PCR). For faecal genotypes from
      wolves in Yellowstone National Park, error rates varied substantially among
      samples, often above the 'worst-case threshold' suggested by simulation.
      Consequently, a substantial proportion of multilocus genotypes held one or more
      errors, despite multiple PCR. These genotyping errors created several genotypes
      per individual and caused overestimation (up to 5.5-fold) of population size. We
      propose a 'matching approach' to eliminate this overestimation bias.

PMID- 12803650
TI  - The use of nuclear and mitochondrial single nucleotide polymorphisms to identify
      cryptic species.
AB  - There is growing interest in the use of single nucleotide polymorphisms for
      evolutionary and population genetics. We tested the efficacy of one of the
      available single nucleotide polymorphism techniques, single-base extension, in
      distinguishing four cryptic species of Microtus. Sequence data were available for
      these species at nuclear and mitochondrial loci and their identity could be
      independently confirmed using karyotypes. We found that the development and
      optimization of single nucleotide polymorphisms required extensive effort, and
      that the method accurately identified the correct nucleotide at single nucleotide
      polymorphism sites approximately 90% of the time at the conserved nuclear locus.
      Correct identification rates were much lower at the highly variable mitochondrial
      locus.

PMID- 12803651
TI  - Molecular evidence for deep phylogenetic divergence in Mandrillus sphinx.
AB  - Mandrills (Mandrillus sphinx) are forest primates indigenous to western central
      Africa. Phylogenetic analysis of 267 base pairs (bp) of the cytochrome b gene
      from 53 mandrills of known and 17 of unknown provenance revealed two
      phylogeographical groups, with haplotypes differentiated by 2.6% comprising seven
      synonymous transitions. The distribution of the haplotypes suggests that the
      Ogooue River, Gabon, which bisects their range, separates mandrill populations in
      Cameroon and northern Gabon from those in southern Gabon. The haplotype
      distribution is also concordant with that of two known mandrill simian
      immunodeficiency viruses, suggesting that these two mandrill phylogroups have
      followed different evolutionary trajectories since separation.

PMID- 12803652
TI  - Interleukin-1 (IL-1) system gene expression in granulosa cells: kinetics during
      terminal preovulatory follicle maturation in the mare.
AB  - BACKGROUND: A growing body of evidences suggests that the ovary is a site of
      inflammatory reactions, and thus, ovarian cells could represent sources and
      targets of the interleukin-1 (IL-1) system. The purpose of this study was to
      examine the IL-1 system gene expressions in equine granulosa cells, and to study
      the IL-1beta content in follicular fluid during the follicle maturation. For this
      purpose, granulosa cells and follicular fluids were collected from the largest
      follicle at the early dominance stage (diameter 24 +/- 3 mm) or during the
      preovulatory maturation phase, at T0 h, T6 h, T12 h, T24 h and T34 h after
      induction of ovulation. Cells were analysed by RT-PCR and follicular fluids were
      studied by gel electrophoresis and immunoblotting. RESULTS: We demonstrated that
      interleukin-1beta (IL-1beta), interleukin-1 receptor 2 (IL-1R2) and interleukin-1
      receptor antagonist (IL-1RA) genes are expressed in equine granulosa cells. We
      observed that the IL-1beta and IL-1RA mRNA content changed in granulosa cells
      during the terminal follicular maturation whereas IL-1R2 mRNA did not vary. In
      follicular fluid, IL-1beta content fluctuated few hours after induction of
      ovulation. CONCLUSIONS: The expression of IL-1beta gene in granulosa cells and
      the follicular fluid IL-1beta content seem to be regulated by gonadotropins
      suggesting that IL-1beta could be an intermediate paracrine factor involved in
      ovulation.

PMID- 12803653
TI  - HLA-A and -B alleles and haplotypes in 240 index patients with common variable
      immunodeficiency and selective IgG subclass deficiency in central Alabama.
AB  - BACKGROUND: We wanted to quantify HLA-A and -B phenotype and haplotype
      frequencies in Alabama index patients with common variable immunodeficiency
      (CVID) and selective IgG subclass deficiency (IgGSD), and in control subjects.
      METHODS: Phenotypes were detected using DNA-based typing (index cases) and
      microlymphocytotoxicity typing (controls). RESULTS: A and B phenotypes were
      determined in 240 index cases (114 CVID, 126 IgGSD) and 1,321 controls and
      haplotypes in 195 index cases and 751 controls. Phenotyping revealed that the
      "uncorrected" frequencies of A*24, B*14, B*15, B*35, B*40, B*49, and B*50 were
      significantly greater in index cases, and frequencies of B*35, B*58, B*62 were
      significantly lower in index cases. After Bonferroni corrections, the frequencies
      of phenotypes A*24, B*14, and B*40 were significantly greater in index cases, and
      the frequency of B*62 was significantly lower in index cases. The most common
      haplotypes in index cases were A*02-B*44 (frequency 0.1385), A*01-B*08 (frequency
      0.1308), and A*03-B*07 (frequency 0.1000), and the frequency of each was
      significantly greater in index cases than in control subjects ("uncorrected"
      values of p < 0.0001, 0.0252, and 0.0011, respectively). After performing
      Bonferroni corrections, however, the frequency of A*02-B*44 alone was
      significantly increased in probands (p < 0.0085). Three other haplotypes were
      also significantly more frequent in index cases (A*03-B*14, A*31-B*40, and A*32
      B*14). The combined frequencies of three latter haplotypes in index patients and
      control subjects were 0.0411 and 0.0126, respectively ("uncorrected" value of p <
      0.0002; "corrected" value of p = 0.0166). Most phenotype and haplotype
      frequencies in CVID and IgGSD were similar. 26.7% of index patients were HLA
      haploidentical with one or more other index patients. We diagnosed CVID or IgGSD
      in first-degree or other relatives of 26 of 195 index patients for whom HLA-A and
      -B haplotypes had been ascertained; A*01-B*08, A*02-B*44, and A*29-B*44 were most
      frequently associated with CVID or IgGSD in these families. We conservatively
      estimated the combined population frequency of CVID and IgGSD to be 0.0092 in
      adults, based on the occurrence of CVID and IgGSD in spouses of the index cases.
      CONCLUSIONS: CVID and IgGSD in adults are significantly associated with several
      HLA haplotypes, many of which are also common in the Alabama Caucasian
      population. Immunoglobulin phenotype variability demonstrated in index cases and
      family studies herein suggests that there are multiple gene(s) on Ch6p or other
      chromosomes that modify immunoglobulin phenotypes of CVID and IgGSD. The
      estimated prevalence of CVID and IgGSD in central Alabama could be reasonably
      attributed to the fact that many HLA haplotypes significantly associated with
      these disorders are also common in the general population.

PMID- 12803654
TI  - Quality control in colorectal cancer screening: systematic microbiological
      investigation of endoscopes used in the NORCCAP (Norwegian Colorectal Cancer
      Prevention) trial.
AB  - BACKGROUND: Endoscopic colorectal cancer (CRC) screening is currently implemented
      in many countries. Since endoscopes cannot be sterilised, the transmission of
      infectious agents through endoscopes has been a matter of concern. We report on a
      continuous quality control programme in a large-scale randomised controlled trial
      on flexible sigmoidoscopy screening of an average-risk population. Continuously,
      throughout a two-year screening period, series of microbiological samples were
      taken from cleaned ready-to-use endoscopes and cultured for bacterial growth.
      RESULTS: 8573 endoscopies were performed during the trial period. Altogether, 178
      microbiological samples (2%) were taken from the biopsy channels and surfaces
      from the endoscopes. One sample (0.5%) showed faecal contamination (Enterobacter
      cloacae), and 25 samples (14%) showed growth of environmental bacteria.
      CONCLUSIONS: Growth of bacteria occurs in a clinical significant number of
      samples from ready-to-use endoscopes. Pathogenic bacteria, however, were found
      only in one sample. Improvement of equipment design and cleaning procedures are
      desirable and continuous microbiological surveillance of endoscopes used in CRC
      screening is recommended.

PMID- 12803656
TI  - Myasthenia gravis.
AB  - BACKGROUND: In myasthenia gravis (MG), the prototypic autoimmune disease,
      antibodies against acetylcholine receptors impair neuromuscular transmission and
      produce weakness. Although recognized for several hundred years, it has only been
      over the last three decades that effective treatments have become available for
      MG. REVIEW SUMMARY: This review summarizes the principles of normal neuromuscular
      transmission, the clinical features of MG, and the tests available for its
      diagnosis. The current treatments for MG are discussed, including possible
      mechanisms of action and a discussion of potential adverse effects. When
      available, evidence-based justification for individual treatment options is
      given, and areas of controversy identified. CONCLUSIONS: Significant improvements
      in the diagnosis and management of MG have been made over the last several
      decades. The available treatments either improve neuromuscular transmission
      directly, or suppress or modulate the pathogenic immune response in MG. Treatment
      is highly individualized and must take into account the severity of disease, the
      presence of other diseases, and the kinetics of response for the available
      treatments. This requires detailed knowledge of the mechanisms of action and
      possible adverse effects for each treatment. However, despite an optimistic
      outlook with modern treatment, the management of MG continues to be plagued by
      lack of efficacy in some, and significant adverse effects in most MG patients.

PMID- 12803655
TI  - The construction and use of bacterial DNA microarrays based on an optimized two
      stage PCR strategy.
AB  - BACKGROUND: DNA microarrays are a powerful tool with important applications such
      as global gene expression profiling. Construction of bacterial DNA microarrays
      from genomic sequence data using a two-stage PCR amplification approach for the
      production of arrayed DNA is attractive because it allows, in principal, the
      continued re-amplification of DNA fragments and facilitates further utilization
      of the DNA fragments for additional uses (e.g. over-expression of protein). We
      describe the successful construction and use of DNA microarrays by the two-stage
      amplification approach and discuss the technical challenges that were met and
      resolved during the project. RESULTS: Chimeric primers that contained both gene
      specific and shared, universal sequence allowed the two-stage amplification of
      the 3,168 genes identified on the genome of Synechocystis sp. PCC6803, an
      important prokaryotic model organism for the study of oxygenic photosynthesis.
      The gene-specific component of the primer was of variable length to maintain
      uniform annealing temperatures during the 1st round of PCR synthesis, and
      situated to preserve full-length ORFs. Genes were truncated at 2 kb for efficient
      amplification, so that about 92% of the PCR fragments were full-length genes. The
      two-stage amplification had the additional advantage of normalizing the yield of
      PCR products and this improved the uniformity of DNA features robotically
      deposited onto the microarray surface. We also describe the techniques utilized
      to optimize hybridization conditions and signal-to-noise ratio of the
      transcription profile. The inter-lab transportability was demonstrated by the
      virtual error-free amplification of the entire genome complement of 3,168 genes
      using the universal primers in partner labs. The printed slides have been
      successfully used to identify differentially expressed genes in response to a
      number of environmental conditions, including salt stress. CONCLUSIONS: The
      technique detailed here minimizes the cost and effort to replicate a PCR
      generated DNA gene fragment library and facilitates several downstream processes
      (e.g. directional cloning of fragments and gene expression as affinity-tagged
      fusion proteins) beyond the primary objective of producing DNA microarrays for
      global gene expression profiling.

PMID- 12803657
TI  - Hyperperfusion encephalopathies: hypertensive encephalopathy and related
      conditions.
AB  - BACKGROUND: Hypertensive encephalopathy (HTE) is a syndrome typified by headache,
      seizures, and neurologic signs associated with increased systemic blood
      pressures; edema in the subcortical white matter is seen on imaging studies and
      is usually reversible, although infarction or hemorrhage may supervene. Based on
      previous work, we theorize that HTE is associated with increased perfusion to the
      brain. Syndromes related to HTE may also be encountered in clinical situations in
      which perfusion to the brain is acutely increased without systemic hypertension
      (i.e., after treatment of high-grade carotid stenoses or large intracranial
      arteriovenous malformations, or in high altitude mountain sickness). We therefore
      refer to these conditions more generally as hyperperfusion encephalopathies
      (HPE). REVIEW SUMMARY: The clinical and radiographic data of 110 patients
      (average age, 50.1 years) who presented at the Brigham and Women's Hospital with
      clinical and radiographic signs of HPE were reviewed; 104 had systemic
      hypertension and 6 had postcarotid endarterectomy hyperperfusion syndrome. Edema
      involved the subcortical white matter and occasionally the cortex in all
      patients. In patients with systemic hypertension, the edema was usually bilateral
      and located predominantly in the occipital lobes; other brain regions included
      the parietal lobes, posterior frontal lobes, cerebellum, and splenium of the
      corpus callosum. The six patients with postcarotid endarterectomy hyperperfusion
      syndrome had edema in the hemisphere ipsilateral to the operated side involving
      the anterior and middle cerebral artery territories. The edema in HPE was
      associated with: increased low attenuation on CT; decreased T(1) and increased
      T(2) signal on MR imaging; increased cerebral perfusion on single emission
      computed tomography (SPECT) and perfusion MR imaging;did not show restricted
      diffusion on MR imaging. The syndrome resolved completely in most cases after the
      administration of antihypertensive agents, although rarely small infarcts and
      hemorrhages occurred. Three patients with thrombocytopenia developed large fatal
      intracranial hemorrhages. CONCLUSION: The symptoms of HPE are usually
      nonspecific, but the radiographic findings are consistent. Treatment should be
      instituted rapidly and patients should be followed until the condition resolves
      either clinically or radiographically; hemorrhagic complications, although rare,
      can be serious.

PMID- 12803658
TI  - Treatment of ruptured intracranial aneurysms by embolization with controlled
      detachable coils.
AB  - BACKGROUND: Neurosurgical clipping used to be the standard method of occluding
      intracranial aneurysms, but controlled detachable coils are increasingly used to
      obliterate aneurysms by endosaccular packing. REVIEW SUMMARY: A systematic review
      of observational studies on embolization with coils showed in patients with a
      ruptured aneurysm a complete occlusion in 52% of aneurysms, independence at
      follow-up in 89% of patients, and a procedure related mortality of 1.1%. There is
      no consensus with regard to the indications for surgical or endovascular
      treatment. A recently published randomized trial on early coiling versus early
      operation did not show any differences in clinical outcome after 3 and 12 months,
      but the small number of patients included precludes firm conclusions. Comparisons
      between endovascular and surgical treatment should not only address safety and
      clinical outcome, but also the long-term angiographic results and the risk of
      recurrent hemorrhage after treatment. In current practice, many patients with a
      basilar bifurcation aneurysm are treated by embolization with coils. In many
      patients with a middle cerebral artery aneurysm operation is the preferred
      treatment. For all other aneurysm locations preference for coiling or clipping
      depends on the clinical condition of the patient, the configuration of the
      aneurysm, and on the experience and skills of the local endovascular and
      neurosurgical team. CONCLUSIONS: Endovascular treatment of intracranial aneurysms
      has gained widespread acceptance. Preference for coiling or clipping depends on
      patient and aneurysm characteristics, and on the local expertise.

PMID- 12803659
TI  - The spectrum of ectopic motor nerve behavior: from fasciculations to
      neuromyotonia.
AB  - BACKGROUND: Ectopic impulses in motor nerves generate clinically and
      electromyographically detectable activity in muscle. These discharges occur in
      the form of isolated fasciculations, as persistent muscle activity in the form of
      myokymia and neuromyotonia, or in fulminant contractions of individual muscles in
      the form of a cramp. In the last 20 years, new studies have helped establish the
      relationship of fasciculations with cramps and neuromyotonia and have identified
      common pathophysiologic mechanisms. REVIEW SUMMARY: Current evidence suggests
      that both cramps and fasciculations originate primarily in the most distal motor
      nerve terminals. In this portion of the axon, the overlying Schwann cells do not
      form a myelin sheath and the blood-nerve barrier is relatively porous. The
      terminal axon is studded with receptors to monitor the release of
      neurotransmitters. Under certain stresses, reinnervation, ionic imbalances, motor
      nerve disease, or pharmacologic challenge, ectopic impulses arise and create
      visible, but sporadic fasciculations. Other circumstances, including muscle
      shortening and dehydration, give rise to more frequent and localized
      fasciculations that can erupt into a painful muscle cramp. The most unusual motor
      ectopic phenomena involves rapidly recurrent discharges in multiple motor nerves,
      giving rise to grouped fasciculations, including myokymia and neuromyotonia.
      Recent studies have implicated toxins, and autoimmune and genetic mechanisms in
      the generation of neuromyotonic and myokymic syndromes. Plasma exchange,
      carbamazepine, and phenytoin have proven helpful in select cases. CONCLUSION:
      These findings indicate that motor nerve hyperexcitability is a fruitful subject
      of clinical and laboratory investigation and that treatment based on underlying
      mechanisms proves beneficial.

PMID- 12803660
TI  - Serum tumor necrosis factor-alpha in Guillain-Barre syndrome and its relation to
      plasma exchange.
AB  - BACKGROUND: To correlate the serum tumor necrosis factor-alpha (TNFalpha)
      concentrations before, during and following plasma exchange in patients with
      Guillain-Barre syndrome (GBS). In this prospective study, 21 GBS patients were
      selected. Patients in clinical stages III to V were subjected to plasma exchange.
      The control group included equal numbers of age-matched patients with other
      neurological diseases and healthy voluntary blood donors. A sandwich ELISA method
      was applied to estimate serum TNFalpha concentrations in test and control groups.
      REVIEW SUMMARY: Twelve GBS patients had elevated serum TNFalpha levels that
      ranged between 74 and 182 pg/mL. All 12 GBS patients showed a steady decrease in
      the TNFalpha concentration following plasma exchange and also showed a positive
      correlation with neurological recovery. CONCLUSIONS: We conclude that serum
      TNFalpha concentrations are elevated in 57.1% of GBS patients and TNFalpha level
      decreases following plasma exchange.

PMID- 12803661
TI  - Tension-type headache.

PMID- 12803662
TI  - Informed consent, competency, and the neurologist.
AB  - BACKGROUND: Obtaining informed consent to treatment is an important medical-legal
      and clinical aspect of neurological practice. REVIEW SUMMARY: This review
      discusses the doctrine of informed consent and its role in neurological practice.
      We first provide an overview of the informed consent doctrine and discuss its
      historical origins and current modern form. The three component elements of
      informed consent--being informed, voluntary, and competent--are presented, with a
      focus placed on the competency element. The increasingly important role of
      informed consent in everyday neurological practice is profiled, with particular
      emphasis on patients with dementia. Recent empirical research is presented on
      loss of consent capacity (competency) in patients with Alzheimer's disease and
      Parkinson's disease. Finally, a conceptually based approach to clinical
      assessment of competency is presented to assist neurologists dealing with these
      issues. CONCLUSIONS: The increasing prevalence of patients with neurodegenerative
      disorders in neurological practice heightens the importance of obtaining valid
      informed consent to treatment.

PMID- 12803663
TI  - Delirium.
AB  - BACKGROUND: Delirium is a serious and often undetected neuropsychiatric syndrome.
      Failure to recognize and manage delirium can lead to longer hospital stays and
      increased morbidity and mortality, especially among the elderly. REVIEW SUMMARY:
      This article reviews definitions and diagnosis. The Diagnostic and Statistical
      Manual of Mental Disorders, 4th edition, and the International Statistical
      Classification of Diseases and Related Health Problems, 10th edition, criteria
      are quite similar in their diagnostic criteria. Risk factors include advanced
      age, preexisting brain disease or cognitive impairment, multiple medications, and
      severe medical problems. Delirium in the elderly can be more subtle and recovery
      more prolonged. Diagnosis is more complex if there is already an underlying
      dementia. An organized approach should be used to discover etiology and in
      ordering appropriate laboratory studies. At the cellular level, delirium is
      considered to be a reversible disregulation of neuronal membrane function. This
      involves a selective vulnerability of certain populations of neurons and
      neurotransmitter dysfunction. Practical treatment issues are reviewed.
      CONCLUSIONS: Despite advances, delirium is usually still diagnosed at the
      bedside. Having an organized approach to diagnosis and understanding the
      underlying pathophysiology should help with overall evaluation and treatment.

PMID- 12803664
TI  - Posterior cortical atrophy.
AB  - BACKGROUND: The term posterior cortical atrophy (PCA) was introduced in 1988 to
      describe five patients with fairly homogeneous, but otherwise unclassified,
      symptoms. These patients showed signs of a slowly progressive dementia bearing
      behavioral and physiologic similarities to Alzheimer's disease, but with notable
      distinctions. Specifically, PCA is characterized by an early onset of visual
      agnosia, followed by some or all components of Balint's syndrome, Gerstmann's
      syndrome, and transcortical sensory aphasia. REVIEW SUMMARY: In this review, the
      history, epidemiology, pathophysiology, neurobehavioral aspects, assessment
      (including neurologic and neuropsychologic), differential diagnosis, and
      treatment recommendations for this disorder are reviewed. CONCLUSIONS: As
      originally defined, PCA appears to be a clinically homogeneous syndrome. The
      cluster of symptoms that are common to virtually all examined cases evidences
      this. Although the behavioral and cognitive properties of the disorder are well
      established, many aspects of PCA remain unclear. Specifically, available research
      and understanding of PCA epidemiology and treatment are highly inadequate. In
      fact, the majority of such information regarding PCA is derived from studies of
      Alzheimer's disease. To a lesser extent, Pick's disease and Creutzfeldt-Jakob
      disease research have also provided insight into the underpinnings of PCA. Until
      PCA is categorically defined as a variant or subgroup of these other
      neurodegenerative disorders, however, such derivations are merely speculations.

PMID- 12803665
TI  - Neuralgic amyotrophy: clinical features and diagnostic evaluation.
AB  - BACKGROUND: Neuralgic amyotrophy is an uncommon neurologic syndrome of unknown
      etiology involving the brachial plexus, which is manifest by shoulder and arm
      pain, weakness, and sensory loss. Because of the diversity and variability of the
      initial features and similarity to other neurologic and non-neurologic disorders,
      patients may initially present to internists, orthopedic surgeons, or
      pulmonologists, and may be initially diagnosed with an alternative disorder.
      REVIEW SUMMARY: Neuralgic amyotrophy occurs at an annual incidence rate of 1 to 2
      cases per 100,000 population. The disorder is most common in adulthood, but
      patients of any age may be affected. Pain is the most common initial symptom and
      is followed by weakness and sensory loss in the distribution of a single nerve or
      diffuse regions of the brachial plexus. Although the exact etiology is unknown,
      many associated factors, such as immunizations, minor trauma, infectious
      diseases, pregnancy, and surgical procedures have been associated with the
      development of the disorder. Evaluation with electrodiagnostic and radiographic
      studies is useful in confirming the diagnosis and excluding alternative
      disorders. No treatment has been definitively proven to improve the course of the
      disorder; however, the overall prognosis is good, with approximately 90% of
      patients demonstrating significant improvement. CONCLUSIONS: Neuralgic amyotrophy
      is an important, potentially debilitating disorder, which may present to
      physicians in multiple specialties. Awareness of this disorder may preclude
      unnecessary testing or surgical procedures and can guide toward appropriate
      treatment with physical therapy. Counseling patients about the overall good
      prognosis can help appease patients' anxiety about a more sinister diagnosis or
      course.

PMID- 12803666
TI  - The neurologic consequences of eclampsia.
AB  - BACKGROUND: Toxemia of pregnancy (preeclampsia/eclampsia) is a syndrome
      characterized by pregnancy-induced hypertension, edema, and proteinuria, although
      it is often associated with more generalized multisystem abnormalities that
      affect the nervous system, the liver, kidneys, and coagulation. For the most
      part, preeclampsia/eclampsia is a reversible process that almost always improves
      after delivery of the baby. Despite recent advances in diagnosis and management,
      eclampsia remains the second most common cause of maternal death in the United
      States. Because of the often severe repercussions on the nervous system,
      neurologists can make important contributions to the management of patients with
      eclampsia. Although preeclampsia is largely under the purview of obstetrics,
      neurologists can provide input to the management of intracranial vascular
      problems, seizures, and raised intracranial pressure. Input on the severity and
      nature of neurologic problems will enable the obstetrician to determine whether
      to expedite or to delay child birth. REVIEW SUMMARY: There is an increasing body
      of evidence on the associated endothelial dysfunction, breakdown of the blood
      brain barrier, and failure of cerebrovascular autoregulation with vasospasm,
      ischemia, and cerebral edema. Therapy is directed at controlling blood pressure,
      giving magnesium sulfate to treat the preeclamptic/eclamptic process itself, and
      instituting antiseizure medicines (e.g., diazepam or phenytoin) when uncontrolled
      seizures or status epilepticus supervene. CONCLUSION: Cerebrovascular accidents
      occur more frequently in young women during pregnancy and the puerperium, and
      there is an unmet need for basic and clinical research directed at the
      pathophysiology of the eclamptic process so as to provide more directed therapy.

PMID- 12803667
TI  - Patient and family fact sheet. Alternative and complementary medicine.

PMID- 12803668
TI  - HTLV-1 and its neurological complications.
AB  - BACKGROUND: Since its discovery in 1980, human T-cell lymphotropic virus type-1
      (HTLV-1) has been associated with a number of neurological diseases. The
      distribution of HTLV-1-associated neurological disease is worldwide. In endemic
      areas, up to 30% of the population may be infected with HTLV-1; however, only a
      small percentage of infected persons develops neurological disease. REVIEW
      SUMMARY: In 1986, HTLV-1 infection was reported in patients of chronic
      progressive myelopathy of uncertain etiology, and the disease entity was called
      HTLV-1-associated myelopathy/tropical spastic paraparesis. Recently, HTLV-1
      infection has been associated with polymyositis and uveitis. Interestingly, a
      single patient may display more than one syndrome. Although other neurological
      syndromes occur in HTLV-1-infected individuals, there is not enough epidemiologic
      data that show a strong association. Treatment of HTLV-1-associated neurological
      disease is challenging, and well-controlled studies are lacking. CONCLUSION: As
      neurologists and other scientists begin to understand the pathophysiology of HTLV
      1 infection, improved therapies should be developed. Randomized trials with
      longer follow-up are required to understand the effect of treatment on disability
      and quality of life.

PMID- 12803669
TI  - The pathophysiology of migraine.
AB  - BACKGROUND: Migraine results from episodic changes in central nervous system
      physiologic function in hyperexcitable brain manifested by abnormal energy
      metabolism, lowered threshold for phosphene generation, and increased contingent
      negative variation. Human functional magnetic resonance imaging and
      magnetoencepholography data strongly suggest that aura is caused by cortical
      spreading depression. REVIEW SUMMARY: Brain hyperexcitability may be caused by
      low magnesium levels, mitochondrial abnormalities with abnormal phosphorylation
      of adenosine 5'-diphosphate, a dysfunction related to nitric oxide, or calcium
      channelopathy. Low magnesium can result in opening of calcium channels, increased
      intracellular calcium, glutamate release, and increased extracellular potassium,
      which may in turn trigger cortical spreading depression. Mitochondrial
      dysfunction has been suggested by a low phosphocreatine:Pi ratio and a possible
      response by migraine patients to riboflavin prophylaxis. Nitroglycerine
      administration results in a delayed migraine-like headache in migraine patients
      but not in control patients, and a nonspecific nitric oxide synthase inhibitor
      aborted migraine at 2 hours in the majority of tested migraine patients compared
      to controls. Many patients with familial hemiplegic migraine have a missense
      mutation in the P/Q calcium channel, so that this form of migraine, at least, is
      associated with a demonstrable calcium channelopathy. CONCLUSIONS: The generation
      of migraine occurs centrally in the brain stem, sometimes preceded by cortical
      spreading depression and aura. Activation of the trigeminovascular system
      stimulates perivascular trigeminal sensory afferent nerves with release of
      vasoactive neuropeptides, resulting in vasodilation and transduction of central
      nociceptive information. There is then a relay of pain impulses to central second
      and third-order neurons and activation of brain stem autonomic nuclei to induce
      associated symptoms.

PMID- 12803670
TI  - Management of acute cervical spinal cord injury.
AB  - BACKGROUND: Spinal cord injury affects approximately 10,000 new persons each year
      in the United States. Motor vehicle crashes, violence, and falls are the most
      common causes. The purpose of this review is to provide a rational management
      strategy for treating acute cervical spinal cord injuries. REVIEW SUMMARY:
      History-taking in these patients should focus on a few key points. Physical
      examination consists of determining the level of the lesion by a tailored motor,
      sensory, and reflex examination. An algorithm for the judicious use of plain
      radiographs, computed tomography scans, and emergent magnetic resonance imaging
      is presented. Management goals include protection of uninjured tissue,
      restoration of reversibly injured tissue, and achieving alignment and permanent
      spinal stability. The role of early surgery and high-dose steroids are discussed.
      CONCLUSION: Maximizing neurological function after cervical spinal cord injuries
      relies on rapid diagnosis and appropriate management. Although prognosis
      generally remains poor, recent advances in the basic sciences offer hope for the
      future.

PMID- 12803671
TI  - Tensilon and the diagnosis of myasthenia gravis: are we using the Tensilon test
      too much?
AB  - BACKGROUND: Tensilon (edrophonium chloride) is a reversible acetylcholinesterase
      inhibitor used in the diagnosis of myasthenia gravis, diagnosis and treatment of
      arrhythmias, detection of early digitalis toxicity, reversal of neuromuscular
      blockade, and other medical conditions. Toxicity associated with Tensilon use has
      appeared in the literature for decades. REVIEW SUMMARY: This review discusses the
      risks of Tensilon and the information practitioners should know before
      administering the drug. We review the literature regarding serious toxicity of
      this drug and offer recommendations for its safe use. CONCLUSIONS: A careful
      medication history should be taken before the administration of Tensilon.
      Additionally, physicians should be aware of appropriate alternative methods of
      diagnosis before choosing to administer Tensilon. Physicians should be aware of
      the clinical situations where the Tensilon test no longer is indicated.

PMID- 12803672
TI  - Ataxias of childhood.
AB  - BACKGROUND: This review examines the causes of ataxias in children. It is a
      relatively common manifestation of neurological diseases in children. The
      etiology of ataxia covers a broad range, from infections to rare hereditary
      metabolic diseases. A systematic approach is required to make the correct
      diagnosis. REVIEW SUMMARY: The more common causes of ataxias in children are
      discussed in detail. The importance of recognizing potentially reversible
      conditions such as vitamin E deficiency and Refsum's disease is stressed. Recent
      advances in molecular genetics of some of the chronic ataxias are discussed. The
      importance of categorizing diseases based on the duration of symptoms and
      associated signs is discussed. Treatment options are mentioned. CONCLUSION:
      Ataxia is a common mode of presentation of cerebellar, posterior column, and
      vestibular disease in children. Awareness of the spectrum of disease entities
      that cause ataxia in childhood may lead to better diagnosis.

PMID- 12803673
TI  - A medical mystery. Atrophy of the caudate nuclei characteristic of Huntington's
      disease.

PMID- 12803674
TI  - Patient and family fact sheet. Peripheral neuropathy.

PMID- 12803675
TI  - Causes and management of thunderclap headache: a comprehensive review.
AB  - BACKGROUND: Thunderclap headache (or sudden severe headache) is an uncommon type
      of headache. Recognition and accurate diagnosis of this headache are important,
      because there is often a serious underlying brain disorder. SUMMARY: In this
      article, causes and management of thunderclap headache are discussed. In the
      primary care setting, there is a serious cause in one third of patients, but in
      the hospital setting, up to two thirds of patients have a serious underlying
      brain disorder. Clues in history and physical examination can point to a possible
      serious underlying cause of thunderclap headache, such as subarachnoid
      hemorrhage, intracranial hematoma, or cerebral venous thrombosis. The remaining
      patients with thunderclap headache, however, have a primary headache disorder,
      such as migraine or (less frequently) tension headache with an unusual sudden
      onset, exertional headache, coital headache, cough headache, or cluster headache.
      The concept of thunderclap headache as a distinct clinical entity is discussed,
      with implications for its evaluation. Present radiological techniques are
      reviewed with regard to their diagnostic utility in detecting a serious brain
      disorder. CONCLUSIONS: Thunderclap headache is an uncommon type of headache, and
      a serious underlying cause should be excluded.

PMID- 12803676
TI  - Approved and future pharmacotherapy for multiple sclerosis.
AB  - BACKGROUND: Pharmacotherapy for relapsing-remitting multiple sclerosis (MS)
      advanced with the demonstration that interferon beta and glatiramer acetate
      improve the clinical course of this disease. Mitoxantrone is the first drug
      approved by the Food and Drug Administration for treatment of secondary
      progressive MS. Despite this progress, the agents presently available are only
      partially effective, are difficult to administer, and may have significant side
      effects. Several orally administered immunomodulatory agents are presently being
      evaluated for treatment of MS. One class of drugs, HMG CoA inhibitors (statins),
      is safe and well-tolerated and could become another mainstay of MS therapy.
      REVIEW SUMMARY: This article reviews the clinical evidence for approved MS
      therapies and discusses their mechanisms of action. Furthermore, the clinical and
      laboratory data suggesting a potential role for statins in MS therapy are
      discussed. CONCLUSIONS: Although treatment with interferon beta, glatiramer
      acetate, and mitoxantrone, the approved therapies, provide important treatment
      options for patients with relapsing-remitting MS and secondary progressive MS,
      the potential benefits of other medications, including statins, should be
      explored in controlled clinical trials.

PMID- 12803677
TI  - A practical approach to the diagnosis and management of MELAS: case report and
      review.
AB  - BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis with stroke-like
      episodes (MELAS) is a mitochondrial disorder and an important diagnostic
      consideration in the young patient with nonhemorrhagic stroke. Its presentation
      is varied and diagnosis is based on early recognition of the clinical features
      and correct interpretation of laboratory and radiologic studies. SUMMARY: In this
      article, we report a patient with MELAS and review the clinical, laboratory, and
      neuroradiologic features of the condition. In the young patient with multiple
      stroke-like episodes in different vascular territories and neuroradiologic
      features of transient abnormalities in varying regions, laboratory testing for
      MELAS must be performed. The presence of ragged red fibers in skeletal muscle and
      biochemical demonstration of defects in mitochondrial respiratory enzymes
      strongly support the diagnosis. Molecular genetic testing for abnormalities in
      mitochondrial DNA will confirm the diagnosis. The importance of a thorough
      assessment of family history is also emphasized. The basic principles of
      mitochondrial genetics and the common point mutations and rearrangements of
      mitochondrial DNA associated with MELAS are reviewed. Although treatment options
      are limited, several therapeutic agents have been studied. CONCLUSIONS: The
      diagnosis of MELAS should be considered in the young patient with stroke,
      especially when accompanied by other clinical features such as seizures,
      encephalopathy, and muscle weakness. Laboratory evaluation can provide an
      accurate diagnosis, especially when the appropriate mitochondrial DNA studies are
      performed. Genetic counseling should be provided to patients with MELAS
      associated with mitochondrial DNA point mutations. Better understanding of the
      molecular basis of the condition may result in the development of effective
      treatment strategies.

PMID- 12803678
TI  - Corticosteroid treatment of mitochondrial encephalomyopathies.
AB  - BACKGROUND: Mitochondrial encephalopathy with lactic acidosis and stroke-like
      symptoms (MELAS) is a multisystem disorder characterized by stroke-like episodes,
      seizures, dementia, headaches,evidence of mitochondrial myopathy. Lactic acidosis
      and ragged red fibers are often present. A variety of therapies have been used
      with inconclusive and disappointing results. There have been very few cases of
      MELAS reported as corticosteroid responsive. SUMMARY: A 27-year-old healthy man
      was hospitalized with recurrent generalized tonic-clonic seizures, intractable
      headaches, and stroke-like symptoms. These symptoms improved after the initiation
      of corticosteroid treatment. Multiple attempts to taper corticosteroids were
      followed by clinical relapse. Genetic testing in this patient revealed a point
      mutation at nt 3243 of the mitochondrial tRNA gene, confirming the diagnosis of
      MELAS. The patient died 1 year later after an episode of status epilepticus.
      Corticosteroid therapy in individual MELAS patients has been associated with
      clinical improvement. Discrepancy exists with regard to corticosteroid type,
      dose, route of administration, length of therapy, patient population, and
      clinical and metabolic parameters to follow during corticosteroid therapy.
      CONCLUSIONS: Corticosteroid therapy may be beneficial during acute exacerbation
      of MELAS.

PMID- 12803679
TI  - Babinski sign.
AB  - Despite all of the medical advances, Babinski sign has proved reliable in precise
      localization of central nervous system dysfunction. It is well accepted that
      Babinski sign is indicative of dysfunction of fibers within the pyramidal tract.
      Joseph Francois Felix Babinski first described the clinical significance of the
      reflex in 1896. He showed that the extensor plantar response was indicative of
      pyramidal dysfunction and that it was absent in hysteria. He also illustrated
      that it was present in infancy and transiently appeared in epilepsy and
      strychnine poisoning. Babinski also pointed to the existence of "formes frustes"
      of his reflex and recognized its occasional absence in patients with other
      clinical signs of pyramidal lesions. The sign emerges when the dysfunction of the
      pyramidal tract involves the fibers that project on motoneurons of foot muscles
      and is mediated by extensor hallucis longus. Babinski sign may not be present
      acutely after transverse lesions of the spinal cord or acute brain lesions
      because of temporary inexcitability of spinal motoneurons.

PMID- 12803680
TI  - Advice for caregivers.

PMID- 12803681
TI  - Intraoperative neuromonitoring.
AB  - BACKGROUND: Intraoperative neuromonitoring (IONM) has been a valuable part of
      surgical procedures for over 25 years. Insight into the nervous system during
      surgery provides critical information to the surgeon allowing reversal or
      avoidance of neural insults. REVIEW SUMMARY: Electrophysiological tests including
      electroencephalography, electromyography, and multiple types of evoked potentials
      (somatosensory, auditory, and motor) are monitored during surgeries that involve
      risk to the nervous system. Deterioration of signals suggests a surgical insult
      and is associated with an increased risk of postoperative deficit. Intraoperative
      identification of this risk allows corrective action. In addition, IONM teams
      make use of their armamentarium of tests to evaluate anatomy or function of the
      nervous system in response to specific questions posed by the surgical team.
      CONCLUSIONS: Intraoperative recordings are now a routine part of many surgical
      procedures. Their correct application leads to improved surgical outcome.

PMID- 12803682
TI  - Disease-modifying therapy in multiple sclerosis: strategies for optimizing
      management.
AB  - BACKGROUND: The objective for this article is to highlight several challenges
      faced by patients and providers in the utilization of disease-modifying agent
      (DMA) therapy in multiple sclerosis (MS) and to offer practical management
      strategies that can effectively mitigate or even prevent limiting adverse
      reactions and enhance treatment compliance. REVIEW SUMMARY: Our discussion will
      be limited to the use of interferon beta1a (Avonex, Rebif), interferon beta1b
      (Betaseron), and glatiramer acetate (Copoxane) as these are the primary agents
      used in the United States for primary disease-modifying therapy in relapsing
      forms of MS. Some of the recommendations contained herein are derived from
      evidence-based studies, while others are contingent upon our collective clinical
      experiences. At the University of Texas Southwestern Medical Center at Dallas and
      Texas Neurology in Dallas we actively follow approximately 5000 MS patients. The
      majority of our patients with relapsing-remitting MS (RRMS) or secondary
      progressive MS (SPMS) are treated with one of the currently available DMAs. Our
      experience with these patients, and the challenges they face in continuing long
      term treatment, constitutes the basis of our proposed treatment strategies. As
      part of this effort we formulated an assessment and intervention instrument that
      can be used in the clinic and by telephone to enhance compliance and minimize
      adverse events. CONCLUSION: A comprehensive treatment approach to the utilization
      of disease-modifying therapy in MS can serve to optimize the management of our
      patients and effectively meet the challenges that arise during the course of
      treatment.

PMID- 12803683
TI  - Review: small-fiber neuropathy.
AB  - BACKGROUND: Most peripheral neuropathies involve large as well as small-fiber
      dysfunction. A small subset of neuropathies present with restricted or
      predominant small-fiber involvement. REVIEW SUMMARY: In this review, we discuss
      the differential diagnosis, clinical presentation, evaluation, and treatment of
      small-fiber neuropathies. Although these neuropathies are rare, their
      differential diagnosis is broad, and includes many disorders, including
      metabolic, toxic, inflammatory, infectious, and genetic etiologies. As small
      fibers subserve pain and autonomic functions, these neuropathies usually present
      with pain and temperature loss, painful dysesthesias, autonomic dysfunction, or a
      combination. These neuropathies are especially challenging as nerve conductions
      and EMG, which help guide the evaluation of most peripheral neuropathies, may
      have normal findings in patients with small-fiber neuropathies. Other specialized
      studies, including tests of autonomic function, intraepidermal nerve fiber
      analysis, and quantitative sensory testing, are often required to confirm the
      presence of a small-fiber neuropathy. In some cases, the underlying etiology can
      be directly treated. In most, management is limited to symptomatic treatment of
      sensory and autonomic dysfunction. CONCLUSION: Small-fiber neuropathies are a
      heterogeneous group of disorders. They vary in etiologies and require special
      attention, as many disorders are rare and the differential diagnosis is broad.
      Evaluation is often extensive and may need pathologic specimen. Many patients
      respond to symptomatic therapy, but some are difficult to treat.

PMID- 12803684
TI  - Gait disorders.
AB  - BACKGROUND: Disorders of gait and mobility are common neurologic abnormalities of
      aging and can have disastrous consequences. Etiology is multifactorial, and
      normal age-related changes are difficult to distinguish from those resulting from
      the disease. REVIEW SUMMARY: Gait evaluation with special techniques provides
      scientific understanding of physiologic mechanisms, but experienced clinicians
      can make diagnoses based on general medical and neurologic history and physical
      examination. Details to observe include posture, length of stride, width of base,
      speed and fluidity of motion, arm swing, bilateral symmetry of motor activity,
      and neurologic signs. Gait disorders are classified into lowest-level, middle
      level, and highest-level disorders. In lowest-level gait disorders, only one
      major afferent system (visual, proprioceptive, or vestibular) is affected and the
      disturbance is usually self-limited or compensated. Middle-level disorders
      include myelopathy from cervical spondylosis; spastic hemiparetic gait from
      unilateral impairment of the corticospinal tract; gaits associated with movement
      disorders; and dystonic, choreic, hemiballistic, and cerebellar ataxic gaits.
      Highest-level gait disorders include cautious gait, subcortical dysequilibrium,
      frontal dysequilibrium, isolated gait ignition failure, frontal gait, primary
      progressive freezing gait, and psychogenic gait disorders. CONCLUSIONS: A
      treatable cause can often be found. Physical therapy with gait evaluation and
      training is recommended. Medication must be kept to a minimum.

PMID- 12803685
TI  - Frontotemporal dementia classification and neuropsychiatry.
AB  - BACKGROUND: Frontotemporal dementia (FTD) is a syndrome encompassing the clinical
      expression of frontal or temporal lobe degeneration. The many clinical phenotypes
      of FTD include primary progressive aphasias and a more common frontotemporal
      degeneration with less marked language alteration but significant behavioral
      changes. SUMMARY: This paper describes the clinical progression of
      neuropsychiatric symptoms among 62 predominantly behavioral presentations and 30
      language presentations of FTD. Disinhibition and depression became common for
      both subject groups over the course of illness. Significantly more cases
      presenting with behavioral changes had apathy and disinhibition. CONCLUSIONS:
      Language presentations of FTD had longer latency to onset of distinct
      neuropsychiatric changes but eventually converge with the phenotype initially
      affected with behavioral change. Clinicians should anticipate such
      neuropsychiatric changes, prepare families for the course of illness in patients
      with either clinical presentation,treat symptomatically with psychotropic
      medications to help families cope with behaviorally disturbed patients.

PMID- 12803686
TI  - Epilepsy genetics.
AB  - BACKGROUND: Epilepsy genetics is a complex and rapidly expanding field that
      involves the contributions and collaborative efforts of geneticists, molecular
      biologists, epidemiologists, and clinicians. REVIEW SUMMARY: This article first
      provides a background review of basic terminology and contributions from the
      fields of epilepsy, genetics, and genetic epidemiology. It further describes the
      evidence for the genetic basis of epilepsy and enumerates the linkage findings
      and epilepsy susceptibility genes reported to date. It then addresses existing
      knowledge about the genetics of electroencephalogram abnormalities and their
      relationship to clinical epilepsy. Finally, it gives guidelines for genetic
      counseling, with attention to patients' frequently asked questions. CONCLUSIONS:
      This review provides a framework for understanding current and future
      investigations in the field of epilepsy genetics and a way to assist and educate
      individuals and families living with epilepsy.

PMID- 12803687
TI  - Management of large hemispheric strokes in the neurological intensive care unit.
AB  - BACKGROUND: Patients with large hemispheric strokes frequently develop neurologic
      deterioration secondary to cerebral edema. Despite supportive care in the
      intensive care unit and traditional forms of therapy for cerebral edema, they
      have a high morbidity and mortality. New forms of therapy are being investigated
      to improve outcome in these patients. REVIEW SUMMARY: This article begins with a
      discussion of the clinical and radiologic features of large hemispheric strokes.
      The role of increased intracranial pressure in neurologic deterioration and the
      predictors of outcome in these patients are reviewed. The various therapeutic
      options for management of cerebral edema in these patients, including the role of
      osmotic therapy, hypothermia, and hemicraniectomy, are explored. CONCLUSIONS:
      Neurologic deterioration in patients with large hemispheric strokes necessitates
      admission to the intensive care unit for management of the airway, blood
      pressure, and cerebral edema. New promising therapies, such as hemicraniectomy
      and hypothermia, need to be further evaluated to define their role in the
      management of these patients.

PMID- 12803688
TI  - Neuromuscular problems in musicians.
AB  - BACKGROUND: Musicians are an occupational (or avocational) group that may on
      occasion have highly specific health care problems apparently caused by or
      adversely affecting instrumental performance. Neurologists have been intimately
      involved in the development of a burgeoning interest in these disorders and,
      because of the nature of the most common symptoms, neurologists can expect to be
      called upon to evaluate such patients. REVIEW SUMMARY: In this review, the most
      common playing-related disorders are discussed. These include the regional pain
      syndromes, primarily involving the neck and upper extremity, the focal
      neuropathies, again predominantly involving the upper extremity, and the focal
      dystonias or occupational cramps, which typically affect the hand or the cranial
      innervated muscles involved in the embouchure (the relationship of the facial
      musculature to the mouthpiece of the instrument). Risk factors contributing to
      the development of these disorders are reviewed, the diagnostic approach is
      described, and the management of these playing-related problems is summarized.
      Aspects in which the instrumental musician may differ from other patients
      commonly seen by the neurologist, particularly with respect to the types of
      problems seen, methods of evaluation, and therapeutic strategies, are emphasized.
      CONCLUSIONS: Many unanswered questions remain in each of these areas.
      Neurologists and neuroscientists are in an excellent position to help fill the
      voids in our knowledge base. It is hoped that the reader will be stimulated to
      participate in this effort.

PMID- 12803689
TI  - Diagnosis and treatment of neurally mediated syncope.
AB  - BACKGROUND: Syncope is caused by a severe but reversible reduction in blood flow
      to the brain stem neurons responsible for supporting consciousness (reticular
      activating system). Neurally mediated syncope, also referred to as vasovagal or
      reflex syncope, is the most frequent cause of loss of consciousness in apparently
      normal subjects. REVIEW SUMMARY: Neurally mediated syncope is believed to be a
      reflex response with afferent, central, and efferent pathways. Characteristic
      autonomic changes in neurally mediated syncope are an increase in parasympathetic
      efferent activity causing bradycardia and a reduction in sympathetic
      vasoconstrictor outflow causing vasodilatation. Premonitory symptoms, such as
      nausea, diaphoresis, abdominal discomfort, and blurred vision, are caused by
      autonomic activation and are distinguishing features of neurally mediated
      syncope. Neurally mediated syncope frequently has a characteristic trigger,
      although this may not be apparent. Testing orthostatic tolerance during passive
      head-up tilt is the best available diagnostic procedure to evaluate patients with
      syncope in whom a cardiac cause has been excluded. In many cases, once the
      diagnosis of neurally mediated syncope is confirmed, it may suffice to reassure
      the patient and teach him to avoid known triggers and to recognize and act upon
      early warning symptoms. Because subjects with neurally mediated syncope may
      potentially be sodium depleted, increasing salt intake can be beneficial in
      improving their orthostatic intolerance. CONCLUSIONS: Neurally mediated syncope
      is the most common form of syncope in healthy adults. The best diagnostic tools
      are the clinical history and passive head-up tilt. The best treatment strategies
      are the avoidance of triggering factors as well as intravascular volume
      expansion.

PMID- 12803691
TI  - Huntington's disease.

PMID- 12803690
TI  - Decompression illness in divers: a review of the literature.
AB  - BACKGROUND: Neurologists may be consulted to diagnose and treat the severe
      neurologic injuries that can occur in divers with decompression illness (DCI).
      REVIEW SUMMARY: Subclinical bubbles form during normal diving activity. DCI, a
      diffuse and multifocal process, results when bubbles cause symptoms by exerting
      mass effect in tissues, or obstructing venous or arterial flow. The lower
      thoracic spinal cord is a commonly affected area of the central nervous system.
      The most commonly described form of brain DCI is cerebral arterial gas embolism
      with middle cerebral artery or vertebrobasilar distribution involvement. Bubbles
      exert secondary damage to the vascular endothelium, causing activation of
      numerous biochemical cascades. CONCLUSIONS: Divers can develop DCI on very short
      dives or in shallow water, even when adhering to protocols. DCI should be
      strongly considered when divers experience pain after diving. Any neurologic
      symptoms after a dive are abnormal and should be attributed to DCI. Even doubtful
      cases should be treated immediately with hyperbaric oxygen (HBO), after a chest x
      ray to rule out pneumothorax. The Divers Alert Network should be contacted for
      emergency consultation. Delay to treatment can worsen outcome; however, the
      overwhelming majority of divers respond to HBO even days to weeks after injury.
      Although DCI is a clinical diagnosis, magnetic resonance imaging, somatosensory
      evoked potentials, single-photon emission tomography, and neuropsychologic
      testing help to document disease and monitor response to therapy. Divers should
      be treated with HBO until they reach a clinical plateau. Complete relief of
      symptoms occurs in 50% to 70% of divers; 30% have partial relief.

PMID- 12803692
TI  - Evaluation and management of the driver with dementia.
AB  - BACKGROUND: The number of older adult drivers with dementia is expected to
      increase over the next few decades. This increase raises public and personal
      safety concerns given the higher crash rates of drivers with a dementing illness.
      However, the identification of drivers with a dementia who may be at risk for a
      crash is difficult, particularly for those in the early stages of dementia.
      REVIEW SUMMARY: Studies examining the correlation of dementia with driving
      outcomes such as motor vehicle crashes are reviewed. The strengths and weaknesses
      of recent consensus statements, published to assist clinicians in evaluating
      drivers with a dementia, are discussed. The authors also review common practices
      currently in use by physicians to identify at-risk drivers, including mental
      status examinations, global dementia rating scales, specialist referral, medical
      evaluations, and the use of caregiver reports and other proxy measures. Legal
      issues, based on the role of the physician, are reviewed along with suggestions
      for driving cessation and education for the caregiver and family. CONCLUSIONS: In
      patients with mild to moderate dementia, the literature indicates that physicians
      would have difficulty in identifying which individuals should not drive.
      Performance-based measures of driving skills, such as on-road driving tests, are
      recommended as a means of assessing driving competency.

PMID- 12803693
TI  - New antiepileptic drugs.
AB  - BACKGROUND: Eight novel anticonvulsant drugs have been introduced in the United
      States in the past 10 years, as well as two new intravenous preparations of
      anticonvulsant drugs. The role of each in the treatment of patients with epilepsy
      is being refined as experience and research data accumulate. REVIEW SUMMARY:
      Gabapentin, tiagabine, and oxcarbazepine are effective for partial seizures,
      whereas felbamate, lamotrigine, topiramate, levetiracetam, and zonisamide treat
      both partial and generalized seizure types. In general, these newer agents differ
      from older agents by relative lack of drug-drug interactions, and many show
      improved tolerability compared with phenytoin and carbamazepine. Each has
      distinguishing features that can prove useful in specific clinical situations.
      Despite limited Food and Drug Administration indications, all are useful in
      monotherapy under certain circumstances. Fosphenytoin avoids the adverse effects
      of intravenous phenytoin vehicle, and intravenous valproate represents a much
      needed option in patients who require rapid loading of this medication.
      CONCLUSIONS: The greater number of antiseizure drugs available today makes it
      possible to tailor treatment to individual patient needs, allowing more patients
      to be free of debilitating adverse effects. Additionally, some patients can
      achieve complete seizure freedom even after failing one or more other
      antiepileptic drugs.

PMID- 12803694
TI  - Clinical review: the differential diagnosis of pain in the quiet eye.
AB  - BACKGROUND: Eye pain, periorbital and retro-orbital pain, and headache or facial
      pain referred to the orbital region are common presenting complaints. REVIEW
      SUMMARY: In this review, we discuss the etiologies of eye pain in the quiet eye,
      which is defined clinically as one with a clear cornea without redness or
      irritation of the conjunctiva or sclera. CONCLUSIONS: The causes of eye pain may
      be divided into two groups: (1) those associated with abnormal localizing
      ophthalmologic and neuro-ophthalmologic findings (including trigeminal
      neuropathies);(2) those with a normal ophthalmologic and neurologic examinations.
      The latter group is further divided into the following subgroups: (1) specific
      short-lasting or long-lasting headache or eye pain syndromes; (2) pain referred
      to the eye from other pathologic processes (secondary eye pain) sometimes distant
      from structures concerned with vision; and (3) pain from orbital, superior
      orbital fissure, cavernous sinus, or intracranial infiltrative, neoplastic, or
      inflammatory disease processes with normal ophthalmologic and neuro
      ophthalmologic exam. Unfortunately, in some patients, no etiology for the pain
      syndrome is discerned and one is left with a diagnosis of idiopathic eye pain,
      eye strain, or atypical facial pain.

PMID- 12803695
TI  - Hepatitis C: a review of its neurologic complications.
AB  - BACKGROUND: Hepatitis C viral (HCV) infection is common in the general population
      and can cause disease in the nervous system. This article reviews the neurologic
      complications associated with this virus. REVIEW SUMMARY: A vasculitic neuropathy
      is the most firmly linked neurologic illness associated with HCV infection. This
      type of neuropathy occurs frequently in the presence of cryoglobulinemia. HCV is
      considered the most common cause of cryoglobulinemia. Other types of neuropathy
      have been rarely reported with HCV infection and this association is less firm.
      In the central nervous system, vasculitis causing stroke appears to complicate
      HCV infection, usually in the setting of cryoglobulinemia. Several reports of
      myelitis, encephalitis,lymphoma are reviewed. HCV may be the etiologic virus of
      progressive encephalomyelitis with rigidity; a rare disorder similar to stiff-man
      syndrome although different because it is progressive and fatal. Treatment of the
      neurologic complications associated with HCV infection is summarized.
      CONCLUSIONS: HCV infection is being increasingly recognized as a probable cause
      of a variety of neurologic disorders. Systematic study of the various therapeutic
      options remains unexplored.

PMID- 12803696
TI  - Neurologic complications of transplantation.
AB  - BACKGROUND: Organ transplantation is one of the most dynamic fields in medicine
      and has evolved into a life-saving option for thousands of patients with
      previously fatal conditions. The posttransplantation clinical course is
      frequently associated with neurologic complications that are usually related to
      pretransplant morbidity, the surgical procedure of transplantation,
      immunosuppression, and opportunistic infection. REVIEW SUMMARY: Neurologic
      complications of organ transplantation may be divided into complications common
      to all types of allografts and complications that are specific for a particular
      type of organ transplantation. The most common complications include seizures,
      opportunistic central nervous system (CNS) infection, metabolic encephalopathy,
      stroke, intracranial hemorrhage, and drug-related adverse events. Opportunistic
      CNS infection may have a subtle presentation and should not be overlooked, as the
      consequences of delayed treatment may be grave. Neurotoxicity of
      immunosuppressive agents is also a frequent cause of neurologic complications and
      may occur in the setting of normal serum drug levels. The clinical course of
      transplant patients is frequently complex, requiring close cooperation between
      the transplant team and specialty consultants. Prolonged survival of transplant
      patients will shift the focus of neurologic complications from acute,
      perioperative to chronic complications of immunosuppression. CONCLUSIONS:
      Neurologic complications of organ transplantation are commonly related to
      opportunistic infection or neurotoxicity of immunosuppressive agents, requiring
      careful titration of immunosuppression. Timely diagnosis of CNS infection or
      other causes of neurologic dysfunction may significantly improve recovery and
      outcome in these patients.

PMID- 12803697
TI  - Sleep disorders.

PMID- 12803698
TI  - Optimal treatment of superficial bladder cancer in 1994.
AB  - Bladder cancer, one of the first cancers associated with industrialization, is
      not unexpectedly increasing in incidence throughout the world. Despite the
      increasing incidence of bladder cancer, mortality has actually decreased in
      recent years. In advanced and metastatic bladder cancer, the
      platinum/methotrexate-based combination of chemotherapy may be responsible for
      this improved survival. However, chemotherapy appears not to have influenced
      survival in patients with superficial disease. Increasing evidence suggests that
      bacillus calmette-Guerin immunotherapy can reduce both disease progression and
      mortality.

PMID- 12803699
TI  - Results and review of EORTC prospective randomized trials for the treatment of
      prostatic carcinoma.
AB  - Since its formation in the 1976, the European Organization for Research and
      Treatment of Cancer Genitourinary group has completed six phase III trails and
      six phase II trials in prostate cancer. Although these studies did not have a
      very strong influence on the management of prostate cancer worldwide or even in
      Europe, they did help investigators to design better studies and to gain some
      insight into the natural disease of the tumor.

PMID- 12803700
TI  - A patient's goal-directed approach to erectile dysfunction and Peyronie's
      disease.
AB  - Because both erectile dysfunction and Peyronie's disease are functional diseases
      and not life-threatening, I believe their diagnosis and treatment can be tailored
      according to the patient's general health, treatment goals and expectations.
      Therefore, I have proposed and used this patient's goal-directed approach in my
      practice for several years with generally satisfactory results.

PMID- 12803701
TI  - Professional liability problems for urologists.
AB  - This article will consist of three segments. There will be a short introductory
      review of trends and activities at the Canadian Medical Protective Association.
      This will be followed by a discussion of current professional liability problems
      facing Canadian urologists. Finally, two emerging issues of special interest to
      urologists will be presented.

PMID- 12803702
TI  - Age-specific reference ranges for serum prostate-specific antigen.
AB  - As more is learned about the biomolecular properties and physiology of the
      glycoprotein, prostate-specific antigen, its clinical usefulness with regard to
      the diagnosis and management of prostate cancer also will improve. Recent
      advances, including the development of the concepts of prostate-specific antigen
      density and velocity as well as the discovery that prostate-specific antigen
      exists in the serum in several molecular forms, will further improve the clinical
      utility of this tumor marker. The even more recent discovery that the serum
      prostate-specific antigen is dependent upon age also has the potential to enhance
      the clinical usefulness of this tumor marker with regard to the early detection
      of prostate cancer.

PMID- 12803703
TI  - Current hypospadias techniques.
AB  - Our experience with hypospadias surgery has changed over the recent five-year
      period. We are using less preputial tubularized island flaps for urethral
      replacement and more onlay island flap procedures. Approximately, 20% of
      hypospadias occurs from the penoscrotal junction to the perineum, while 30% occur
      in the mid portion of the penis. Fifty percent are distal penile or subcoronal
      (Figure1). There are different operative procedures to repair these varying types
      of hypospadias.

PMID- 12803705
TI  - Guest editorial.

PMID- 12803704
TI  - Surgery for female stress urinary incontinence.
AB  - With the advent of magnetic resonance imaging, the treatment of female
      incontinence has undergone a renaissance. This change has primarily been due to
      superior understanding of anatomy and function of the supports of the urethra,
      bladder neck and bladder base in the female pelvis.

PMID- 12803706
TI  - Impact of pathologic extraprostatic disease on local and systemic progression
      following radical prostatectomy.
AB  - Fifty patients underwent radical prostatectomy for localized prostate cancer
      (Stages A2, B) between 1977 and 1982. Surgical specimens were examined for tumor
      grade and extraprostatic extension of the disease. Forty-one of the 50 patients
      had capsular involvement (82%), 26 (52%) positive margins and 14 (28%) seminal
      vesicular involvement. Six patients progressed locally, six systematically and
      three both. Eight patients progressed at five years and an additional seven at
      ten years. In all 15 progressors tumor involved the capsule yet four patients
      with capsular involvement alone progressed. Eleven of the 26 patients (42%) with
      positive margins progressed. Five of the 14 patients (37%) with seminal vesicle
      involvement progressed, all five had positive margins as well. None of the
      patients with disease confined within the capsule progressed. Gleason score for
      non-progressors ranged between three and nine with a median of six while for
      progressors it ranged between five and nine with a median of seven. Long rank
      test and Cox Proportional Hazard Model statistical analysis were employed among
      all the factors: capsular involvement, positive margins, positive seminal
      vesicles and grade of tumor. Positive margins was the only statistically
      significant factor affecting local progression of the disease in both univariate
      and multivariate analysis at a 95% confidence (p=0.04). All factors were
      statistically insignificant in affecting systemic progression (p>0.5).

PMID- 12803707
TI  - Hereditary prostate cancer in Nova Scotia.
AB  - A case control study of 244 prostate cancer patients and 240 of their female
      partners was performed. The study sample was generated by the following methods:
      1) an advertisement was placed in two newspapers with province-wide distribution
      2) all Nova Scotia urologists were asked to identify patients with a positive
      family history and 3) consecutive patients treated for prostate cancer in an
      ambulatory setting were contacted by telephone. Seven men and 27 women did not
      know their family history. Patients with a positive family history (43/237, 18%)
      became case group. Wives who had family members affected by prostate cancer
      (16/213, 7.5%) comprised the control group. Both cases and controls completed a
      standardized questionnaire by mail or telephone. The heredity variant of prostate
      cancer accounted for 5 %, the familial 12% and the sporadic 83% of cases studied
      and 0%, 9% and 91%, respectively of the control group. The odds ratio calculated
      for first-and second-degree relatives was 2.73 (95% confidence interval, 1.49
      5.01). The mean age at diagnosis of these cases was 68 years. There was not a
      statistically significant difference between the familial (69 years) and
      hereditary (67 years) subgroups' mean age at diagnosis (p=0.4). Most men with
      prostate cancer in the Nova Scotia population sample were affected by the
      sporadic variant. Small but important groups were affected by familial or
      hereditary types. Identification of these families will have important
      implications for screening and gene mapping studies.

PMID- 12803709
TI  - Transition zone carcinoma of the prostate.
AB  - Transition zone carinoma of the prostate can present a difficult diagnostic
      challenge. This entity should be considered in patients who have high prostate
      specific antigens (PSA) in relation to prostate volume and negative transrectal
      ultrasounds and ultrasound-guided biopsies. A transurethral biopsy of the
      prostate may be necessary to obtain the diagnosis.

PMID- 12803708
TI  - Urinary retention in sexually abused women.
AB  - Urinary retention is generally believed to be the result of neurogenic or non
      neurogenic problems. In men, it is often caused by benign prostatic hypertrophy
      which can be treated by transurethral surgery.1 In women, however, studies have
      shown that urinary retention is usually caused by detrusor dysfunction rather
      than obstruction. Surgery on the urethra or bladder neck is, therefore,
      inappropriate and ineffective. Once the cause of retention has been determined
      (i.e whether neurogenic or non-neurogenic in origin), appropriate treatment can
      be decided upon. The most common neurogenic problems are diabetes mellitus,
      multiple sclerosis and spinal cord pathologies.(1) Patients with non-neurogenic
      etiology associated with urinary retention are often found to have psychosocial
      problems that inhibit detrusor activity causing psychogenic retention.1-4 Studies
      have found that woman with a history of psychosis, depression and stress/anxiety
      have a higher incidence of urinary retention than woman with no history of such
      conditions. Psychological problems involving the loss of loved one, recent
      marriage break-up, abortion, pelvic surgery, etc. have been found to contribute
      to the incidence of urinary retention. There is another group of women who may or
      may not exhibit psychological problems associated with psychogenic urinary
      retention, but who may develop the same physical manifestations. These women have
      been sexually abused and have not fully resolved or realized the trauma of the
      assault. This paper looks at four cases or urinary retention in sexually abused
      woman, the treatments used and the results and conclusions obtained.

PMID- 12803710
TI  - Benign scrotal inclusion cyst of the male perineum: an unusual post-operative
      complication.
AB  - Common complications after cystourethrectomy include wound infection, pneumonia,
      pyelonephritis and ureteral obstruction. No perineal cysts have been reported. We
      describe a perineal cystiic mass excised 14 years after cystourethrectomy. The
      cyst was lined by keratinizing stratified squamous epithelium with prominent rete
      ridges and basal pigmentation. A subjacent, concentric layer of smooth muscle was
      evident. An eccrine sweat gland was present in the cyst wall. Taken together, the
      features strongly suggest a scrotal inclusion cyst, a hitherto undescribed
      entity. Although rare, this lesion could masquerade as a local recurrence of
      carcinoma.

PMID- 12803711
TI  - Editorial.

PMID- 12803712
TI  - Interstitial brachytherapy for penile carcinoma: an alternative to amputation.
AB  - From 1987 to 1994, 15 patients with penile saquamous cell carcinoma were referred
      to the Ottawa Regional Cancer Centre. Seven had already been managed surgically.
      The other eight were treated with interstitial implantation. Mean age was 58
      years (range 39-80). Two patients had previous incomplete local excision and six
      had biopsy only, with tumor from 1.5 to 4 cm in diameter. Six tumors were located
      on the glans, one on the corona and one at the base. All were clinically node
      negative. Six patients were implanted using a rigid technique with a fixed array
      of steel needles in pre-drilled plexiglass templates, and two with flexible nylon
      tubing. Implants were manually afterloaded with Iridium-192 wire. The prescribed
      dose of 60-65 Gy was delivered in 2.5-5.5 days. Local tumor control is 100% at a
      mean follow-up of 37 months (range 6-64). One patient died of metastases at 15
      months with the primary controlled. The remaining seven patients are alive
      without evidence of disease. Six who were sexually active, continue to be so. One
      patient has a urethral stricture requiring dilatations. Cosmesis is generally
      good: mild to moderate hypopigmentation, telangiectasia and fibrosis may develop
      at the implant site. Intersititial brachytherapy for T1 or minimally invasive T2
      penile squamous cell cercinoma up to 4 cm in diameter provides excellent local
      control with preservation of function and is a viable alternative to amputation.

PMID- 12803713
TI  - Upper urinary tract videourodynamics: a more complete Whitaker test.
AB  - A modification of the Whitaker test is described using only a single nephrostomy
      tube for both inflow and pressure measurement. The technique also includes
      ureteral transit time and fluoroscopic imaging. This technique has been used in
      ten patients, all of whom had symptoms and/or imaging suggesting obstruction.
      Five patients had no obstruction on testing with true renal pelvic pressures </=
      10 cm of H20 at all times. Five patients were obstructed (four distally and one
      proximally) with true renal pelvic pressure >20cm. This technique requires only
      one access port into the renal pelvis. The addition of fluoroscopy and ureteral
      transit time considerably aided our interpretation of the test. These
      modifications have made the Whitaker test more complete.

PMID- 12803714
TI  - Racial influence in renal stone disease: a Saskatchewan story.
AB  - Data was obtained from two separate governement sources in an effort to review
      the prevalence of kidney stone disease in the province of Saskatchewan for the
      years 1983-1988 inclusive. The data revealed a statistally significant difference
      in prevalence rate among different ethnic groups within the population.
      Aboriginal people were found to have a prevalence rate approximately one-third
      that of the nonaboriginal (non-native) population. A renal stone episode
      prevalence of 0.858 per 1000 population compared to 0.222 per 1000 population in
      aboriginal people (p.<.001). The reasons for this difference could not be
      retrospectively associated with geographical variation. A discussion of other
      possible causes in association is offered, but it is felt that, in the end, more
      research into this area is required.

PMID- 12803715
TI  - Venovenous bypass in renal cell carcinoma with caval tumor thrombus.
AB  - We describe two patients with a T3bN2M0 renal cell carcinoma with caval extension
      to the hepatic veins in which we successfully utilized extracorporeal
      femoralaxillary venovenous bypass for tumor thrombus resection. The inherent
      advantage of this modified venovenous bypass are discussed with a current review
      of the literature.

PMID- 12803716
TI  - An unusual pelivc mass: cystic fibroadenoma of the prostate.
AB  - Cystic fibroadenoma is an extremely rare benign lesion of the prostate. Herein we
      report a case of such a lesion in a 52-year-old man initially thought to have
      locally advanced prostate cancer.

PMID- 12803717
TI  - Caring for the "orphan" cancers.

PMID- 12803718
TI  - Prostate-related symptoms in Canadian men 50 years of age and older: attitudes
      and consulting behaviors.
AB  - The objectives of this study were (1) to characterize the knowledge about the
      prostate gland, the attitudes towards the prostate problems, medications and
      physicians and the consulting behaviors of Canadian men 50 years of age or older;
      and, (2) to identify individual groupings based on these characteristics. A
      population-based, epidemiologic study of Canadian men 50 years of age or older,
      identified by a modified random digit dialing method, was undertaken via home
      telephone interviews. A total of 19 359 calls yielded a probability sample of 508
      Canadian men 50 years of age or older who could participate in the study. A
      cluster analysis was conducted to determine whether respondents could be
      categorized based on their responses and attitudes. The results of the study
      indicate that many educational opportunities exist with regard to urinary
      complaints of men 50 years of age or older. Furthermore, it may be possible to
      identify individuals who will be more difficult than others to educate and treat.

PMID- 12803719
TI  - Plant extracts in the medical management of benign prostatic hyperplasia: fact or
      fiction?
AB  - The objective of this study was to critically review the published literature on
      the role of phytotherapeutic agents and phytosterols (also referred to as plant
      extracts) in the medical management of benign prostatic hyerplasia. Data sources
      included a bibliographic database that was searched to retrieve articles on
      benign prostatic hyperplasia with a time constraint of 1985-1993. Indexing terms
      used included plant extracts, phytosterols, cernilton, paraprost and medical
      management. Studies selected were randomized trials incorporating plant extracts.
      English abstracts were reviewed for articles published in other languages and
      these reviews are noted. English articles were critically reviewed based on study
      design, patient selection, length of follow up, postulated mechanisms of action
      and benign prostatic hyperplasia subjective and objective outcome measures. A
      number of plant extracts are being used in the management of benign prostatic
      hyperplasia, predominantly in Europe. These plant extracts, which are
      biochemically heterogenous, have been found to act through a variety of
      mechanisms: an anti-inflammatory effect, a decrease in globulin, a direct
      cytotoxic effect, anti-prolactin activity and bladder compliance modification.
      More importantly, these plant extracts have not been associated with the side
      effects of chemical castration. Their alleged efficacy may be based upon a
      mechanism which is currently not understood and a combination of these extracts
      with accepted medications may have the potential of improving the overall
      efficacy of medical therapy in the treatment of benign prostatic hyperplasia.
      Despite the shortcomings of the published trials, there is enough evidence to
      warrant additional study in the form of randomized control trials using
      scientific validated outcome measures. Using validated scores with patients of
      mild to moderate symptomatology would help to further elucidate the relative
      efficacy of cernilton, curbicin and permixon.

PMID- 12803720
TI  - Pathological review of female patients undergoing cystectomy for cancer of the
      bladder.
AB  - The female patient undergoing cystectomy for invasive cancer of the bladder
      usually has some form of diversion to the skin. Recently, in the male patient
      there has been a major shift from cutaneous diversion to functioning orthotopic
      urethral reservoirs so that the patient can void per urethra. We were intrigued
      by Bartsch's anatomical studies of the female urethra. With this new information,
      it seemed feasible to perform the orthotopic urethral diversion in the female. In
      order to have guidelines in choosing which patients could undergo cystectomy
      preserving the urethra, we reviewed the pathological findings on female patients
      undergoing cystectomy at Vancouver General Hospital for 10 years.

PMID- 12803721
TI  - Pediatric urethropelvic junction obstruction - an update.
AB  - Maternal-fetal ultrasound has dramatically increased the detection of
      asymptomatic ureteropelvic junction obstruction. Techniques to assess obstruction
      and function in the pediatric kidney are imperfect and only recently have
      diuretic renography and ultrasound been standardized. Considerable controversy
      has arisen regarding the need for and appropriate timing of surgical correction
      in pediatric asymptomatic ureteropelvic junction obstruction. Experimental
      research has suggested that the reninangiotensin system and perhaps growth
      factors play a role in the response to congenital asymptomatic ureteropelvic
      junction obstruction. Until several large-scale prospective clinical studies in
      North America and Britain come to fruition, many aspects of this condition will
      remain poorly understood.

PMID- 12803722
TI  - Fournier's gangrene: nine cases of necrotizing infection of the male genitalia.
AB  - Between 1989 and 1993, nine patients with Fournier's gangrene presented to our
      institution. The mean patient age was 66 years. The source of infection was
      dermal in five cases, urethral in three cases and rectal in one case. Potential
      contributing factors included diabetes mellitus in six cases, alcohol abuse in
      four cases and drug-induces immunosuppression in two cases. In every patient,
      tissue cultures revealed mixed aerobic and anaerobic infections. All patients
      were treated initially with aggressive surgical debridement and culture-specific
      intravenous antibiotics. One patient required multiple debridements.
      Reconstruction by split-thickness skin grafts was performed in eight cases and
      one healed by secondary intention. There were no deaths due to progressive
      infection. The mortality rate was 11% with six month follow-up. The favorable
      outcome of patients in this series supports the current recommendation for early,
      aggressive surgical debridement and culture-specific, intravenous antibiotic
      therapy.

PMID- 12803723
TI  - Localized amyloidosis of the urethra presenting as painful erection.
AB  - Localized amyloidosis of the urethra is a rare condition that usually produces
      obstructive voiding symptoms and /or hematuria. We report the unique case of a
      man who presented with painful erections. He was managed successfully by local
      endoscopic excision.

PMID- 12803724
TI  - The BPH marketplace.

PMID- 12803725
TI  - Asymptomatic microscopic hematuria.
AB  - The detection of microscopic hematuria on routine urinalysis in a patient with no
      urological symptoms presents the urologist with a management dilemma. Many
      authors1-6 have recommended intravenous pyelography (IVP) or renal ultrasound,
      and cystourethroscopy as the minimum investigation in all patients with this
      finding. While recognizing that microscopic hematuria may represent an early sign
      of a life threatening but curable urological cancer, urologists are also aware
      that a full urological investigation in most of these patients will not detect a
      life-threatening lesion. Under these circumstances, it is understandable that the
      urologist may be reluctant to subject every patient asymptomatic microscopic
      hematuria to an IVP and cystourethroscopy. Factors that may influence the
      urologist include the recognition that a certain number of erythrocytes (RBCs) in
      the urine may be accepted as within normal limits, and associated elements in the
      urine such as protein, or red cell or granular casts suggest a glomerular as
      opposed to a urological cause for the hematuria. The purpose of this review is to
      clarify our understanding of the normal limits of microscopic hematuria, to
      review recently introduced techiniques that may be helpful in determining that
      the hematuria is of glomerular origin, and to examine the data on which
      recommendations for patients investigation is advisable, it is necessary to
      address the question of which investigation are most appropriate, and whether
      under any circumstances, any investigations can be safely omitted.

PMID- 12803726
TI  - Efficacy of cranberry in prevention of urinary tract infection in a susceptible
      pediatric population.
AB  - The objective of the study was to evaluate liquid cranberry products as
      prophylaxis against bacterial urinary tract infection in a pediatric neuropathic
      bladder population. Forty cases managed by clean intermittent catheterization
      with or without pharmacotherapy were enrolled in a randomized single-blind cross
      over study. Subjects ingested 15 mL/kg/day of cranberry cocktail or water for six
      months followed by the reverse for another six months. Initial catheter urine
      samples and subsequent monthly and interim cultures were obtained. Associated
      symptoms were recorded along with follow-up attendance/compliance registry. The
      number of negative culture months to the number of months contributed was
      tabulated and compared between interventions. Individual, cumulative and
      antimicrobial subset analysis was performed. Twenty one patients completed the
      study;12 dropped out for reasons related to the cranberry (taste, caloric load
      and cost); seven patients dropped out for other reasons (parents too busy, death,
      no stated reason). Wilcoxon matched-pairs Signed-ranks analysis revealed no
      difference between intervention periods (2-tailed P=.5566 [whole group]; p=.2845
      [antimicrobial subset]) with respect to infection. Fewer infections were observed
      in nine patients taking cranberry juice and in nine patients given water; no
      difference was noted in three. Liquid cranberry products, on a daily basis, at
      the dosage employed, did not have any effect greater than that of water in
      preventing urinary tract infections in this pediatric neuropathic bladder
      population.

PMID- 12803727
TI  - Multiple biopsies of the prostatic bed following radical prostatectomy to assess
      accuracy of reported resection margins.
AB  - Selected biopsies were obtained from the prostatic bed following radical
      prostatectomy in 35 patients with clinically localized prostate cancer in order
      to address and understand the high incidence of positive resection margins. The
      biopsies were obtained from the urethra, bladder neck and left and right
      posterolateral regions of the patient's prostatic bed after the specimen was
      removed. Pathologically 28 out of 35 (80%) had positive resection margins, yet
      only five out of 35 patients (14.2%) had positive prostatic bed biopsies
      (residual tumors). None of the patients with negative pathological margins had
      positive bed biopsies. The urethra was the most common site of residual tumor.
      Gleason score was comparable in those with negative or positive biopsies. Tumor
      volume and prostatic-specific antigen level were highest in those with positive
      prostatic bed biopsies. We recommend routine four-point prostatic bed biopsies
      following radical prostatectomy.

PMID- 12803728
TI  - A vesicouterine fistula caused by catheterization during delivery.
AB  - We report a case of a vesicouterine fistula occurring after catheterization
      during delivery in a women who had two previous Caesarian sections. Fistulae
      between the bladder and uterus are rare; they have been reported after prolonged
      and neglected labor 1 and after caesarian section. 2 This case followed catheter
      penetration of the bladder and thinned cervix during delivery.

PMID- 12803729
TI  - Orchidectomy and hormonal therapy of prostate cancer.
AB  - The objective of this study is to document the use of hormonal therapies in
      treating prostate cancer in Ontario in the last decade. Drug utilization data
      were extracted from the Ontario Drug Benefit Program, while surgical orchidectomy
      rates were calculated from Hospital Medical Records Institute data. The
      provincial rate of orchidectomy showed a 55% relative increase from 1981 to 1991.
      There was a 6.4-fold variation in orchidectomy rates among counties in Ontario.
      As well, the expenditures on new hormonal therapies rose 38-fold between 1985 and
      1990, and doubled between 1990 and 1992. There was no consistent relationship
      between use of orchidectomy and hormonal drug therapy at the county level. We
      conclude that both forms of hormonal therapy have increased in Ontario. The wide
      variation in surgical orchidectomy rates observed in Ontario suggests differences
      in practice styles and possible medical uncertainty. Guidelines for the hormonal
      therapy of prostate cancer may be a helpful step forward for practitioners and
      patients.

PMID- 12803730
TI  - Microscopic hematuria - dealing with the dilemma.

PMID- 12803731
TI  - The effects of GPIIb-IIIa antagonists and a combination of three other
      antiplatelet agents on platelet-leukocyte interactions.
AB  - The effects of the GPIIb-IIIa antagonists abciximab and MK-852 on platelet
      leukocyte interactions in vitro were studied and the results compared with those
      obtained with a combination of aspirin, dipyridamole and AR-C69931 (Asp/Dip/AR
      C). Platelet-monocyte (P/M) and platelet-neutrophil (P/N) conjugate formation
      increased when blood was stirred or a platelet agonist was added. Leukocyte
      activation also occurred as judged by expression of surface tissue factor antigen
      and CD11b. Abciximab and MK-852 potentiated P/M, especially when collagen was
      used. They also increased the amount of tissue factor on the monocytes, but not
      CD11b. The Asp/Dip/AR-C did not enhance P/M or tissue factor exposure. Augmented
      tissue factor expression on monocytes in the presence of a GPIIb-IIIa antagonist
      may be relevant to the increased mortality associated with trials of such
      antagonists when given orally in patients with vascular disease. The Asp/Dip/AR-C
      was superior to abciximab and MK-852 in inhibiting platelet and leukocyte
      function.

PMID- 12803732
TI  - Atorvastatin affects C-reactive protein levels in patients with coronary artery
      disease.
AB  - BACKGROUND: Elevated levels of C-reactive protein (CRP) are considered to be one
      of the indicators of poor prognosis in coronary artery disease (CAD). The aim of
      this study was to evaluate anti-inflammatory effects of atorvastatin in patients
      with CAD by measuring serum CRP levels. METHODS: After measuring the baseline
      levels of CRP and lipid fractions, the patients were divided into two groups. In
      Group A (n = 46), atorvastatin (20 mg/day) was administered in addition to
      classic antianginal treatment (beta-blocker, nitrate and aspirin). In Group B (n
      = 32), the usual antianginal treatment was continued. Following 4 weeks of
      treatment the same measurements were repeated. RESULTS: In Group A, CRP decreased
      from 20.3 mg/dl (95% CI, 9-31.8) to 10.8 mg/dl (95% CI, 2.7-18.9) (p < 0.001). In
      Group B, CRP decreased from 17 mg/dl (95% CI, 13.1-21) to 12.8 mg/dl (95% CI, 9.7
      15.9) (p < 0.01). The decrease in group A was more than in group B (p = 0.003).
      CONCLUSIONS: In patients with CAD, atorvastatin exerted an anti-inflammatory
      effect represented by decreasing CRP levels. This effect was independent of the
      change in low density lipoprotein cholesterol (LDL-C) or high density lipoprotein
      cholesterol (HDL-C) levels.

PMID- 12803733
TI  - Are the metabolic effects of rosiglitazone influenced by baseline glycaemic
      control?
AB  - OBJECTIVE: To compare the metabolic effects of rosiglitazone, an antidiabetic
      agent of the thiazolidinedione class, in patients with type 2 diabetes with fair
      to moderate glycaemic control (glycosylated haemoglobin (HbA(lc)) < 9%) and poor
      glycaemic control (HbA(lc) > or = 9%). RESEARCH DESIGN AND METHODS: Data were
      pooled from two 26-week, randomised, placebo-controlled, double-blind studies of
      rosiglitazone (4 and 8 mg/day). RESULTS: After 26 weeks of treatment, HbA(lc) was
      significantly reduced (p < 0.05) compared with baseline and placebo in patients
      taking rosiglitazone 8 mg/day for both HbA(lc) stratifications, with greater
      reductions in patients with baseline HbA(lc) > or = 9%. After 26 weeks of
      treatment, reductions in fasting plasma glucose (FPG) were significant (p < 0.05)
      compared with baseline and placebo in both rosiglitazone treatment groups for
      both HbA(lc) stratifications, with greater reductions in the group with poor
      glycaemic control. Rosiglitazone significantly improved insulin sensitivity (p <
      0.05) compared with baseline in patients with baseline HbA(lc) < 9%.
      Rosiglitazone significantly improved beta-cell function (p < 0.05) compared with
      baseline with more improvement in the group with baseline HbA(lc) > or = 9%.
      These improvements were statistically significant compared with placebo,
      regardless of HbA(lc) stratification. CONCLUSION: Rosiglitazone significantly
      improved HbA(lc) and FPG levels in patients with type 2 diabetes, with the
      greatest improvements observed in patients with baseline HbA(lc) levels > or =9%.

PMID- 12803734
TI  - Post-traumatic stress disorder: symptom profiles in men and women.
AB  - OBJECTIVE: To investigate the symptom frequencies of a relatively large sample of
      post-traumatic stress disorder (PTSD) sufferers and compare male and female
      symptom profiles. RESEARCH DESIGN AND METHODS: A total of 103 consecutive
      attendees at a clinic for PTSD were examined using a checklist of DSM-IV PTSD
      characteristics. The presence and absence of all symptoms was evaluated in a
      research interview. Some additional symptoms were also routinely asked about,
      such as mood lability, substance use, sex drive or libido. Symptom profiles of
      male and female sufferers of PTSD were compared using the chi-squared statistical
      test. MAIN OUTCOME MEASURES: Structured interview using checklist of DSM-IV PTSD
      characteristics. RESULTS: Certain symptoms were present in more than 30% of
      sufferers. Symptom frequencies for anxiety, insomnia, distressing and recurrent
      dreams, flashback imagery and intrusive thoughts, irritability, poor
      concentration, avoidance behaviour and detachment all reached frequencies above
      70%. Some symptoms (such as inability to recall parts of the trauma and
      restricted affect) occurred in no more than 35% of sufferers. CONCLUSIONS: Men
      are significantly more likely than women to suffer with irritability (p < 0.05)
      and to use alcohol to excess (p < 0.05). Symptoms tend to follow an acute stress
      reaction, occur early and persist for many months. A case is made for restricting
      the diagnosis to the most prevalent symptoms and for including some often
      overlooked symptoms in the diagnostic guidelines, namely low mood, mood lability,
      and impaired libido.

PMID- 12803735
TI  - Value of rilmenidine therapy and its combination with perindopril on blood
      pressure and left ventricular hypertrophy in patients with essential hypertension
      (VERITAS).
AB  - OBJECTIVES: The primary objective was to assess the effects of rilmenidine
      monotherapy and in combination with perindopril on blood pressure (BP) in
      patients assessed with grade 1 or 2 essential hypertension. The study also
      examined the effects of 2-year rilmenidine monotherapy on left ventricular
      hypertrophy (LVH) and on diastolic function of the left ventricle, along with the
      effects of rilmenidine on left ventricular mass index in hypertensive patients
      with no LVH, and the relationship between BP reduction and any change in LVH.
      RESEARCH DESIGN AND METHODS: Mild-to-moderate hypertensive patients (n = 500)
      were enrolled in a multicentre 2-year open study and treated with rilmenidine (1
      2 mg per day) monotherapy or rilmenidine plus perindopril (2, 4 or 8 mg per day)
      if control of hypertension was not achieved with rilmenidine monotherapy within
      12 weeks. Blood pressure was recorded at regular intervals by the investigators
      and LVH measured by centralised single-blind echocardiographic reading. RESULTS:
      Rilmenidine monotherapy (average dose 1.42 mg) produced a significant decrease in
      BP from the baseline of 163 +/- 10/100 +/- 5 mmHg to 134 +/- 10/86 +/- 7 mmHg at
      1 year and to 136 +/- 10/84 +/- 7 mmHg at 2 years (p < 0.001 for both). In 188
      patients with LVH, the left ventricular mass index was significantly reduced from
      161.4 +/- 30.5 to 131.3 +/- 26.5 at 1 year and to 134.1 +/- 26.0 g/m(2) at 2
      years (p < 0.001 for both). Addition of perindopril to those patients whose BP
      was not normalised by rilmenidine monotherapy after 12 weeks further decreased BP
      significantly from 150 +/- 13/93 +/- 8 mmHg to 142 +/- 14/89 +/- 7 mmHg at the
      end of the 2nd year. CONCLUSIONS: Long-term rilmenidine monotherapy was shown to
      be efficient in controlling BP and in reducing LVH. The addition of perindopril
      to rilmenidine monotherapy proved to be effective and well tolerated in those
      patients who did not respond to rilmenidine alone.

PMID- 12803736
TI  - The development of an oral antidiabetic combination tablet: design, evaluation
      and clinical benefits for patients with type 2 diabetes.
AB  - Type 2 diabetes is a chronic and progressive disease. Oral antidiabetic
      monotherapies directly address only one defect as their primary mechanism of
      action, and do not control blood glucose sufficiently well to meet current
      glycaemic targets. In consequence, most patients need combination therapy within
      a few years. However, the co-administration of two or more oral antidiabetic
      drugs may render treatment regimens difficult to follow. Combining oral
      antidiabetic agents into a single tablet provides a means of intensifying
      antidiabetic therapy while supporting good patient compliance. An insulin
      sensitiser and an insulin secretagogue represent a rational oral antidiabetic
      combination, as they address the dual endocrine defects of insulin resistance and
      impaired beta-cell function in type 2 diabetes. Nevertheless, the components of a
      combination tablet must be carefully chosen. Metformin (an insulin sensitiser)
      and glibenclamide (an insulin secretagogue) are well supported by decades of
      clinical evidence, and the pharmacokinetics of these agents support twice-daily
      co-administration. The final technical challenge is to optimise their delivery
      within a single-tablet combination. A recently-introduced metformin-glibenclamide
      combination tablet (Glucovance) has been extensively studied in well-designed
      clinical trials, where it has been shown to be more effective than its component
      monotherapies in controlling fasting and postprandial glycaemia. This treatment
      provides a case study in the development of a single-tablet oral antidiabetic
      combination, in terms of the pharmacokinetic issues facing the development of
      this preparation, and the implications of the pharmacokinetic properties of the
      components of the combination tablet on their pharmacodynamic actions and risk
      benefit profile.

PMID- 12803737
TI  - Treatment of mild-to-moderate hypertension with calcium channel blockers: a
      multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine.
AB  - BACKGROUND: Hypertension is one of the most important causes of cardiovascular
      disease, and treatment of hypertension leads to a significant reduction in
      cardiovascular mortality and morbidity. Although calcium channel blockers are
      regarded as an important part of the therapeutic armamentarium against
      cardiovascular diseases, and are among the most frequently prescribed
      antihypertensive medications, concern has been aroused about these drugs,
      particularly the short-acting dihydropyrldine derivatives. However, the value of
      nifedipine GITS(Adalat-Crono), the long-acting dihydropyrldine, is in need of
      being re-established. OBJECTIVE: To compare the effectiveness, safety and
      tolerability of once-daily nifedipine and amlodipine treatment in patients with
      mild-to-moderate essential hypertension. DESIGN: Randomised multicentre trial
      with an open comparison of treatments for 12 weeks, with a preceding placebo run
      in period of 2 weeks (patients on beta-blockers at the time of enrollment entered
      a mandatory 2-week wash-out period before being allowed In the placebo run-in
      period;this wash-out period was one week for patients using any antihypertensive
      medication other than beta-blockers). SETTING: Nine centres (all university
      hospitals) in Turkey. PATIENTS: 155 patients with essential
      hypertension(diastolic blood pressure 95-109 mmHg). INTERVENTIONS: Initial
      treatment (step 1) consisted of 30 mg nifedipine GlTS (n = 76; (Adalat-Crono
      tablets), or 5 mg amlodipine (n = 79; Norvasct5-mg tablets), either administered
      once daily, as a morning dose, or f the blood pressure was not below 140/90 mmHg,
      or the reduction In diastolic blood pressure was lower than 10 mmHg after a
      treatment period of 6 weeks, the dose was increased (Step 2) to 60 mg once daily
      in the nifedipine group, or 10 mg once daily in the amlodipine group. MAIN
      EFFICACY PARAMETER: Diastolic blood pressure at trough after 12 weeks of active
      compound therapy adjusted to baseline. RESULTS: After 12 weeks of treatment, the
      mean diastolic blood pressure was 83.1 and 81.9 mmHg,in the nifedipine and
      amlodipine groups, respectively (p = 0.436). The mean decrease in systolic blood
      pressure (28.5 +/- 11.9 and 28.2 +/- 11.2 mmHg in the nifadipine and amlodipine
      groups, respectively) and the mean decrease in diastolic blood pressure (16.4A +/
      7.0 and 17.5 +/- 6.9 mmHg in the nifedipine and amlodipine groups,
      respectively), as well as the responder rates (88.1%and 92.1%, in the nifediplne
      and amlodipine groups, respectively) were comparable at the end of the study. No
      significant differences between groups were detected In the efficacy parameters
      assessed in this study. Both drugs were well tolerated. The overall incidence of
      adverse events was 7.9% in the nifadipine group and 10.1% In the amlodipine
      group. However, more patients discontinued treatment prematurely in the
      amlodipine group (13 patients; 19.7%), than in the nifedipine group (four
      patients; 5.6%). CONCLUSIONS: The results of this study demonstrated that once
      daily nifedipine in GITS formation and amlodipine are comparably safe and
      effective treatment options in patients with mild-to-moderate essential
      hypertension.

PMID- 12803738
TI  - Retroperitoneal haematoma and tinzaparin.

PMID- 12803739
TI  - HIV transmission through breastfeeding: problems and prevention.
AB  - The greatest burden of HIV infection in women and their children is
      disproportionately borne by the poorest countries, especially in sub-Saharan
      Africa. Breastfeeding is a major health-promoting factor for infants and children
      in developing countries but the risk of mother-to-child transmission (MTCT) of
      HIV by this route is challenging traditional practices and health policies in low
      resource countries. Maternal and infant factors contributing to the risk of MTCT
      through breastfeeding are still poorly understood and not well researched.
      Factors identified include: advanced clinical stages of infection in the mother;
      high maternal plasma HIV-1 load; presence of mastitis; and infant oral thrush. In
      many developing countries, international agencies are providing support and
      recommendations for preventing MTCT of HIV-1 by breastfeeding. Preventive
      strategies supported by WHO/UNICEF and charitable agencies in some sentinel
      centres in sub-Saharan Africa include routine antenatal voluntary counselling and
      testing (VCT), PCR testing of infants of seropositive mothers at 6 weeks of age,
      various combinations of a shortened period (3-6 mths) of exclusive breastfeeding,
      perinatal administration of antiretrovirals (ARV) such as nevirapine and
      provision of affordable and safe infant replacement feeds (presently given free
      by UNICEF in some centres). Many problems, however, have hindered effective
      implementation of these interventions. In many poor communities, even where VCT
      facilities are available, acceptance of HIV testing is low because there is fear
      of stigmatisation by the spouse, family or community and compliance with complex
      drug regimens is therefore poor. Other problems include the exorbitant cost of
      antiretroviral drugs, inadequately resourced health care systems and
      unavailability or poor acceptance of safe breast-milk alternatives. The rate of
      mixed feeding is high and so the risk of MTCT is increased. Continued promotion
      of exclusive breastfeeding for at least 6 months, irrespective of HIV status,
      followed by a properly prepared, high energy, nutritious complementary diet, with
      the possibility of early weaning to an animal milk formula, still appears to be
      the most appropriate option for the poor in countries with high levels of MTCT
      not deriving any benefit from the above strategies. While a longer period of
      breastfeeding would probably increase the risk of MTCT in vulnerable communities,
      a shorter duration would certainly increase infant morbidity and mortality.
      Results of investigations of the efficacy of ARV for protecting the infants of
      HIV-infected mothers during the breastfeeding period are awaited.

PMID- 12803740
TI  - Growth patterns and survival rates of twins in a rural area of Ghana: a follow-up
      study from birth to adulthood.
AB  - This prospective and descriptive study was conducted to evaluate the growth and
      survival of twins during childhood and adolescence in the Agogo area of Ghana. It
      describes the outcome in 422 twin children born between 1969 and 1981. By 3 years
      of age, 40 (9.5%) of them had not reported again, fifteen of the remaining 382
      had died and 367 (96%) were still alive. In 1993 and 2001, at 12-26 years of age,
      33 children could not be traced; of the remaining 349 children, 17 more had died
      and 317 (91%) were still alive. Incremental weight gain in the 1st year of life
      was approximately 0.17 kg/month less than that of a reference group of USA twins.
      However, growth velocity was similar in the 2nd and 3rd years. From 6 to 36
      months of age, Agogo twins were 0.9-1.3 kg lighter than a reference group of
      Agogo singletons. In both males and females, the physiological growth spurt of
      puberty occurred approximately 2 years later than in Agogo singletons. By
      adulthood, mean heights and weights, particularly of female twins, still lagged
      behind those of the local reference group. Twins have a good chance of surviving
      childhood although they can be considered to be at high risk, particularly during
      the 1st year of life. Up to adulthood, growth potential seems to be less than
      that of their singleton counterparts.

PMID- 12803741
TI  - Hearing impairment in children with impacted cerumen.
AB  - The aim of this study was to determine whether children in whom impacted cerumen
      had been removed were at greater risk of hearing impairment than those without a
      history of impacted cerumen. A retrospective study was conducted in 113 subjects
      and their pair-matched controls taken from a population of 359 randomly selected
      school entrants who received otoscopic, audiometric and tympanometric
      evaluations. It was found that children from whom impacted cerumen had been
      removed were more likely to have hearing loss (p = 0.0001), and of a more
      permanent nature (p = 0.002). They were also likely to have more otitis media
      with effusion (OME) (p = 0.045). Children with a history of impacted cerumen are
      therefore at greater risk of subsequent hearing problems and of a more permanent
      nature than those without, notwithstanding the removal of such impacted cerumen.
      The prevention of cerumen impaction should be of significant public health
      concern in the management of hearing impairment in children, especially where
      there is no routine and systematic screening for hearing disorders.

PMID- 12803742
TI  - Urinary tract infection in febrile children with sickle cell anaemia in Ibadan,
      Nigeria.
AB  - A prospective study to determine the prevalence of bacteriuria and bacterial
      isolates in the urine of febrile children with sickle cell anaemia (SCA) was
      carried out at University College Hospital, Ibadan. Altogether, 171 febrile
      children (aged 1-15 years) with SCA and 171 age- and sex-matched controls were
      studied. After obtaining a history of the illness from the parents or guardians,
      each child was physically examined and a mid-stream urine specimen collected and
      subjected to microscopy and culture. The prevalence of bacteriuria in children
      with SCA was 21.6% compared with 15.8% in the controls. Escherichia coli and
      Klebsiella species were the predominant isolates from the urine, accounting for
      64.9% and 18.9%, respectively, of the isolates from the SCA group and 63% and
      22.2%, respectively, in the controls. In the SCA group, significant bacteriuria
      also occurred with other conditions such as pneumonia and osteomyelitis. Urinary
      tract infection (UTI) is common in children with SCA. Routine screening for it is
      therefore recommended during febrile illnesses. Children with fever from other
      overt causes, however, should not be exempted from the urine screening procedure
      in case there might be concomitant UTI.

PMID- 12803743
TI  - Counting respiratory rate in infants under 2 months: comparison between
      observation and auscultation.
AB  - The World Health Organization's global programme for the control of acute
      respiratory infections relies on counting respiratory rate (RR) by observing
      abdominal and chest movements in order to diagnose pneumonia. However, few
      studies on the reliability of the observation method have been published. We
      counted RR simultaneously by observation and auscultation in 100 healthy infants
      at 1, 2, 4, 6 and 8 weeks of age for 15, 30 and 60 sec, and compared RRs obtained
      by the two methods. In all the age groups studied, the co-efficients of variation
      for the RRs recorded by observation or auscultation were similar. The mean RR by
      observation was higher by 1-3 breaths/min than mean RR by auscultation (p <
      0.001). The 95% confidence interval (+/-2 SD) for the difference between RR by
      the two methods ranged from +5 to -8 breaths/min for RR counted for 1 full
      minute. Our data support the assumption that observation is as reliable as
      auscultation for counting RR.

PMID- 12803744
TI  - A review of neurological disorders presenting at a paediatric neurology clinic
      and response to anticonvulsant therapy in Gambian children.
AB  - A clinical review of 128 children presenting at the paediatric neurology clinic
      of the Royal Victoria Hospital, The Gambia was conducted between July 2001 and
      January 2002. The aim was to assess the spectrum and burden of neurological
      disease presenting at this tertiary-level clinic and to evaluate the
      effectiveness of anticonvulsant therapy. The principal clinical diagnoses most
      frequently made were seizures (57%), neuromotor problems (15%) and developmental
      delay (11%). Many children also had associated developmental delay or learning
      difficulties (55%), speech and language problems (42%) and physical disability
      (36%). Although 65% were considered to need assistance in the community, only 11%
      were receiving such help. There were 73 children with seizures, 80% of whom had a
      greater than 50% reduction in seizure frequency following the start of simple
      anticonvulsant medication. Of the children who had experienced more than 100
      convulsions during the previous year, only 50% responded similarly to treatment.
      This review emphasises the need for improved community services and accessible
      medical care for children with neurological problems in West Africa.

PMID- 12803745
TI  - A child with neurobrucellosis.
AB  - An 11-year-old boy presented with chronic meningitis followed by acute flaccid
      paralysis. The aetiology remained uncertain until the brucellar serology test
      became positive and there was a good response to specific antimicrobial therapy.
      Nerve conduction studies confirmed a proximal radiculopathy. Awareness of the
      condition and performance of the appropriate tests will differentiate
      neurobrucellosis from other chronic central nervous system infections.

PMID- 12803746
TI  - Bilateral pneumothorax complicating miliary tuberculosis in children: case report
      and review of the literature.
AB  - An 11-year-old boy presented with a 4-week history of fever and 2 weeks later
      developed a cough with breathlessness. His chest X-ray showed bilateral miliary
      shadows with pneumothorax on the left side. While on antituberculous therapy
      which was started on admission, he developed right-sided pneumothorax with
      significant collapse of the left lung. He was managed by tube thoracotomy with
      underwater seal but died 4 hours after the procedure was completed.

PMID- 12803749
TI  - Introduction: Cultures of child health in Britain and the Netherlands in the
      twentieth century.

PMID- 12803750
TI  - Vigorous, pure and vulnerable: Child health and citizenship in the Netherlands
      since the end of the nineteenth century.

PMID- 12803747
TI  - Oedema and ascites associated with acute diarrhoea caused by giardia.

PMID- 12803751
TI  - Child health, national fitness, and physical education in Britain, 1900-1940.

PMID- 12803752
TI  - Educational reform, citizenship and the origins of the School Medical Service.

PMID- 12803753
TI  - Child health, commerce and family values: the domestic production of the middle
      class in late-nineteenth and early-twentieth century Britain.

PMID- 12803754
TI  - Health and the medicalisation of advice to parents in the Netherlands, 1890-1950.

PMID- 12803755
TI  - 'Grown-up children': understandings of health and mental deficiency in Edwardian
      England.

PMID- 12803756
TI  - Mulock Houwer's 'Education for responsibility': a chapter from the Dutch history
      of institutional upbringing.

PMID- 12803757
TI  - The healthy citizen of empire or juvenile delinquent?: Beating and mental health
      in the UK.

PMID- 12803758
TI  - Children's emotional well-being and mental health in early post-second world war
      britain: the case of unrestricted hospital visiting.

PMID- 12803759
TI  - The problem of sex education in the Netherlands in the twentieth century.

PMID- 12803760
TI  - 'Tall, spanking people': the idealisation of adolescents in a Dutch therapeutic
      community.

PMID- 12803761
TI  - In the name of the child beyond.

PMID- 12803762
TI  - Pharmaceutical strategies to prevent ventilator-associated pneumonia.
AB  - The increasing incidence of hospital-acquired (nosocomial) infection is a
      disturbing phenomenon resulting in significant patient mortality and putting
      considerable strain on healthcare budgets and personnel. One particularly serious
      aspect of nosocomial infection is that of ventilator-associated pneumonia (VAP).
      This arises in patients who receive mechanical ventilation within the intensive
      care unit. The quoted incidence of VAP varies widely (5-67%) and the reported
      mortality of patients with VAP is in the range of 24-71%. This review will
      examine the many factors that account for these wide ranges reported, including
      the patient population under investigation, the causative organism, the method of
      diagnosis, interventions employed and preventative strategies. The use of
      bioactive and drug-impregnated biomaterials for endotracheal tube construction is
      discussed as novel approaches to the prevention of VAP.

PMID- 12803763
TI  - Intestinal drug absorption and bioavailability: beyond involvement of single
      transport function.

PMID- 12803764
TI  - Thermal gelation of aqueous curdlan suspension: preparation of curdlan jelly.
AB  - Curdlan jelly was prepared by heating an aqueous curdlan suspension at 70 degrees
      C for 5 min. Theophylline, as a model drug, was entrapped in the jelly network.
      Curdlan jelly had a hardness comparable with that of commercially available jelly
      for confectionary. Syneresis was observed for 8 days after the preparation and
      was not detected during the experimental term from the gel prepared from 10% w/v
      curdlan suspension. Release of theophylline from the jellies was sustained, and
      was increasingly delayed with an increase in the curdlan concentration. An
      aqueous curdlan suspension was studied by means of differential scanning
      calorimetry (DSC) up to 80 degrees C and down to -25 degrees C, and subsequent re
      heating to 30 degrees C. Enthalpy increased with the concentration of curdlan,
      while the temperature at the onset of the endothermic peak decreased with the
      concentration of curdlan. The enthalpy due to thermal gelation of 1 mg curdlan
      was 12.2 mJ. An increase in curdlan concentration decreased the enthalpy and
      lowered the onset temperature of the endothermic peak during the DSC re-heating
      scan. The results are due to an increase in the amount of non-freezing water and
      freezing bound water and a decrease in free water. The number of water molecules
      entrapped in the curdlan jelly as non-freezing water was 8.1 per glucopyranose
      residue.

PMID- 12803766
TI  - Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene
      deliveries: effects on serum stability and transfection efficiency.
AB  - In this study, we modified cationic liposomes either by polyethylene glycol (PEG)
      grafting or PEG-adding methods, and compared the physical properties of
      transfection complexes and transfection efficiency in-vitro and prolonged
      circulation in-vivo. The PEG-grafted transfection complexes were prepared by
      mixing plasmid DNA with PEG-grafted cationic liposomes, which were composed of
      DSPE-PEG 2000 and cationic lipids. The PEG-added transfection complexes were
      prepared by adding DSPE-PEG 2000 to the mixture of cationic liposomes and plasmid
      DNA. The particle sizes of the PEG-modified transfection complexes (approximately
      200 nm) changed a little over 4 weeks compared with the conventional transfection
      complexes. In the presence of serum, the transfection efficiency of the
      conventional transfection complexes was lowered whereas the transfection
      efficiency of the PEG-modified transfection complexes was maintained. Moreover,
      the transfection efficiency of the conventional transfection complexes was
      significantly reduced when they were stored. However, the transfection efficiency
      was stable for the PEG-modified transfection complexes, even after two weeks of
      storage. Of the in-vitro transfection efficiencies, there was no difference
      between PEG-grafted and PEG-added transfection complexes. When the conventional,
      PEG-grafted, and PEG-added transfection complexes were administered into mice by
      the tail vein, the PEG-added transfection complexes showed a prolonged
      circulation of plasmid DNA compared with other transfection complexes. These
      results suggest that the PEG-added transfection complexes could be a useful non
      viral vector because of their simplicity in preparation, enhanced stability and
      prolonged circulation compared with the conventional transfection complexes.

PMID- 12803765
TI  - Can the USP paddle method be used to represent in-vivo hydrodynamics?
AB  - Experiments in-vitro and in dogs were conducted to find in-vitro hydrodynamic
      conditions that can be used to represent gastrointestinal motility patterns.
      Specifically, the dissolution performance of micronised and coarse-grade
      felodipine (a poorly soluble, neutral, lipophilic drug) was studied in a
      biorelevant medium in the USP paddle apparatus at various paddle speeds. Ratios
      of percentage dissolved (slower:faster rev min(-1)) were calculated pairwise.
      These ratios were then compared with AUC ratios obtained in a corresponding
      pharmacokinetic study in Labradors, in which the absorption of both the
      micronised and coarse-grade felodipine had been compared under two
      gastrointestinal hydrodynamic conditions. Using a paddle speed combination of 75
      and 125 rev min(-1) to represent the motility patterns in response to
      administration of normal saline and 5% glucose, respectively, the in-vitro ratios
      (75:125 rev min(-1) dissolution ratio was 91% for the micronised and 46% for the
      coarse-grade powder) showed good agreement with the pharmacokinetic data (saline
      to-glucose absorption ratio was 98% for the micronised and 46% for the coarse
      grade powder). It was concluded that, provided an appropriate composition is
      chosen for the dissolution test, the USP paddle apparatus can be used to reflect
      variations in hydrodynamic conditions in the upper gastrointestinal tract.

PMID- 12803767
TI  - Design and validation of a dynamic flow model simulating encrustation of
      biomaterials in the urinary tract.
AB  - A number of models exist for assessing encrustation on biomaterials employed as
      devices in the urinary tract. However, static urine models are suitable only for
      assessment of biomaterials residing in the bladder and the dynamic models
      available suffer from a number of disadvantages, notably their complexity and
      limitation to short-term assessment. The dynamic model described herein is a
      relatively simple design incorporating the ability to assess a large number of
      biomaterials in replicate fashion and over long periods of time. The biomaterials
      tested in the dynamic model conform to the urethral catheter and ureteral stent
      devices that experience urine flow within the urinary tract. The model was
      initially validated using Percuflex as a test biomaterial. The mass of calcium
      and magnesium, representing hydroxyapatite and struvite encrustation,
      respectively, on Percuflex was detected by atomic absorption spectrometry. No
      significant differences in encrustation levels were detected either between
      vessels or between biomaterial positions on any mandrel within the vessels,
      indicating the suitability of the dynamic model for reproducible determination of
      biomaterial encrustation. The dynamic model was then used to compare the
      encrustation of biomaterials commonly employed in urinary-tract devices, namely
      polyurethane, Percuflex and silicone. Calcium and magnesium levels on
      polyurethane and Percuflex were shown to be statistically similar, whereas
      silicone exhibited significantly reduced encrustation. When, subsequently,
      comparisons were made of biomaterial encrustation between the dynamic model and a
      static model, calcium and magnesium levels arising from the latter model were
      significantly higher on each of the biomaterials. However, the same rank order of
      encrustation resistance was observed for the biomaterials in both models, with
      silicone performing better than polyurethane or Percuflex. The prediction of in
      vivo performance based on in-vitro models of encrustation is often difficult,
      although the model described provides a more accurate method for assessing the
      potential of novel and existing biomaterials for use in urinary medical devices
      requiring flow of urine.

PMID- 12803768
TI  - Effect of severe protein-calorie malnutrition on the penetration kinetics of
      trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats.
AB  - This study shows the effect that severe malnourishment has on the kinetics of
      antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old,
      were randomly divided into eight groups. Five groups of experimental rats were
      severely malnourished (SM) and three further groups were considered well
      nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole
      (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart
      puncture and five organs were extracted 0-24 h after the administration of the
      drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in
      fluids. The elimination half-life for trimethoprim from plasma was longer in SM
      rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in
      SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P
      < 0.05). Tissue penetration was much higher for trimethoprim, with penetration
      indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case
      of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657
      for SM rats. Similarly, the penetration ratio to muscle and heart tissue was
      lower in SM rats. However, penetration to kidney, lung, liver and spleen was
      greater in SM rats. It is evident that severe SM decreases the capacity of
      trimethoprim more importantly than sulfamethoxazole biotransformation.

PMID- 12803769
TI  - The increased intestinal absorption rate is responsible for the reduced hepatic
      first-pass extraction of propranolol in rats with cisplatin-induced renal
      dysfunction.
AB  - The mechanisms responsible for the increased bioavailability of propranolol in
      renal dysfunction were investigated in rats. Experimental acute renal failure
      (ARF) was induced by intraperitoneal injection of cisplatin (5 mg kg(-1)). ARF
      induced a significant increase in blood propranolol concentration after intra
      intestinal administration. The extent of bioavailability (F) of propranolol at an
      intestinal dose of 15 mg kg(-1) was 16.4% and 26.9% in control and ARF rats,
      respectively, and the F value at a 37.5 mg kg(-1) dose was 54.7% and 81.4% in
      control and ARF rats, respectively. In contrast, the blood propranolol
      concentration following intraportal infusion was not increased significantly in
      ARF rats. The hepatic first-pass extraction (E(h)) was dose-dependent and
      saturable: E(h) of propranolol in control rats was 58.0% and 18.3% at 8 and 20 mg
      kg(-1), respectively, and E(h) in ARF rats was 50.8% and 19.9% at 8 and 20 mg kg(
      1), respectively. The initial absorption rate of propranolol from the intestine
      in ARF rats was significantly greater compared with control rats. These results
      indicated that the increased bioavailability of propranolol in rats with
      cisplatin-induced renal dysfunction was mainly a result of the increased
      absorption rate in the intestine followed by the partial saturation of hepatic
      first-pass metabolism.

PMID- 12803770
TI  - Estimation of absorption parameters from the non-steady-state phase in the rat
      gut perfusion model.
AB  - The aim of the study was to calculate absorption parameters, including
      permeability coefficients (P(app)), from the non-steady-state portion of the
      outflow to inflow concentration ratio vs time profiles and compare them with
      those obtained via the more traditionally used steady-state phase. The rat in
      situ intestinal perfusion method was used. The compounds studied, diclofenac and
      macrogol 4000 (polyethylene glycol (PEG) 4000), were perfused at four different
      flow rates (0.1-2.0 mL min(-1)). The estimates of P(app) from the non-steady
      state data were systematically lower for both compounds. The non-steady-state
      analysis gave estimates of the intestinal radius, r. The internal diameter of the
      intestine segment increased as the flow rate increased. When this effect was
      taken into account similar P(app) estimates were obtained by the two approaches.
      Thus the convention of using a constant value of intestinal radius in the steady
      state equation leads to an over estimate of the P(app) when high flow rates are
      employed. The different trends observed, between P(app) and perfusate flow rate,
      for the two compounds, macrogol 4000 and diclofenac, may be linked to increased
      surface area and exposure to membrane pores of larger size. The longitudinal
      spreading coefficient, De, increased with flow rate and was approximately 1000
      times greater than that estimated for molecular diffusion. The high values
      obtained were consistent with the non-smooth biological surface and peristaltic
      movement present in-vivo.

PMID- 12803771
TI  - Direct, differential-equation-based in-vitro-in-vivo correlation (IVIVC) method.
AB  - A new, differential equation-based in-vitro-in-vivo correlation (IVIVC) method is
      proposed that directly relates the time-profiles of in-vitro dissolution rates
      and in-vivo plasma concentrations by using one- or multi-compartment
      pharmacokinetic models and a corresponding system of differential equations. The
      rate of in-vivo input is connected to the rate of in-vitro dissolution through a
      general functional dependency that allows for time scaling and time shifting. A
      multiplying factor that accounts for the variability of absorption conditions as
      the drug moves along is also incorporated. Two data sets incorporating slow-,
      medium-, and fast-release formulations were used to test the applicability of the
      method, and predictive powers were assessed with a leave-one-formulation-out
      approach. All fitted parameters had realistic values, and good or acceptable fits
      and predictions were obtained as measured by plasma concentration mean squared
      errors and percent AUC errors. Introduction of step-down functions that account
      for the transit of the dosage form past the intestinal sites of absorption proved
      useful. By avoiding the integral transforms used in the existing deconvolution-
      or convolution-based IVIVC models, the present method can provide increased
      transparency, improved performance, and greater modelling flexibility.

PMID- 12803772
TI  - Quantitative structure-activity relationship (QSAR) analysis of cationic
      complexes of heart perfusion imaging agents and subsequent proposition of two
      different uptake mechanisms.
AB  - Some physicochemical and quantum-chemical discriptors of two series of cationic
      complexes of heart perfusion imaging agents ([(99m)Tc(I)(NO)Cl(PL)(2)](+) and
      [(99m)Tc-Mine](+) series) have been obtained using a semi-empirical quantum
      mechanics method - ZINDO/1. Quantitative structure-activity relationships (QSARs)
      between these descriptors and heart uptake were investigated by multiple linear
      regression analysis method, as the result of which, several equations were
      obtained. Fairly complete new heart uptake mechanisms, redox mechanism for
      [(99m)Tc(I)(NO)Cl(PL)(2)](+) series and passively transport mechanism for
      [(99m)Tc-Mine](+) series are proposed based on the results shown in the
      equations.

PMID- 12803773
TI  - Synthesis and hydrolytic behaviour of 2-mercaptoethyl ibuprofenate-polyethylene
      glycol conjugate as a novel transdermal prodrug.
AB  - Thiolated derivatives of ibuprofen and its polyethylene glycol ester were
      synthesized via condensation of 2-mercaptoethyl ibuprofenate with carboxy
      terminated polyethylene glycol. The release of ibuprofen from this polymeric
      prodrug has been studied under conditions simulating those encountered in the
      skin. The polymeric prodrug of ibuprofen was found to undergo pH-dependent
      hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH
      8.5 (15% at pH 7.4) after 48 h at 37 degrees C. The polymer-drug conjugate was
      subjected to enzymatic hydrolysis in human plasma. The polymer showed
      considerable enzymatic hydrolysis (68% after 48 h). The results showed that the
      polymeric prodrug model of non-steroidal anti-inflammatory drugs (NSAIDs)
      described here can be used in topical formulations of NSAIDs. It is expected that
      the novel thiol derivative will have both enhanced transdermal penetration and
      stability to oxidation which make it a suitable candidate for transdermal
      formulations.

PMID- 12803774
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit vascular smooth muscle
      cell proliferation via differential effects on the cell cycle.
AB  - Abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role
      in the pathogenesis of both atherosclerosis and restenosis. Recent studies
      suggest that high-dose salicylates, in addition to inhibiting cyclooxygenase
      activity, exert an antiproliferative effect on VSMC growth both in-vitro and in
      vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAIDs) exert
      similar antiproliferative effects on VSMCs, and do so via a common mechanism of
      action, remains to be shown. In this study, we demonstrate that the NSAIDs
      aspirin, sodium salicylate, diclofenac, ibuprofen, indometacin and sulindac
      induce a dose-dependent inhibition of proliferation in rat A10 VSMCs in the
      absence of significant cytotoxicity. Flow cytometric analyses showed that
      exposure of A10 cells to diclofenac, indometacin, ibuprofen and sulindac, in the
      presence of the mitotic inhibitor, nocodazole, led to a significant G0/G1 arrest.
      In contrast, the salicylates failed to induce a significant G1 arrest since flow
      cytometry profiles were not significantly different from control cells. Cyclin A
      levels were elevated, and hyperphosphorylated p107 was present at significant
      levels, in salicylate-treated A10 cells, consistent with a post-G1/S block,
      whereas cyclin A levels were low, and hypophosphorylated p107 was the dominant
      form, in cells treated with other NSAIDs consistent with a G1 arrest. The
      ubiquitously expressed cyclin-dependent kinase (CDK) inhibitors, p21 and p27,
      were increased in all NSAID-treated cells. Our results suggest that diclofenac,
      indometacin, ibuprofen and sulindac inhibit VSMC proliferation by arresting the
      cell cycle in the G1 phase, whereas the growth inhibitory effect of salicylates
      probably affects the late S and/or G2/M phases. Irrespective of mechanism, our
      results suggest that NSAIDs might be of benefit in the treatment of certain
      vasculoproliferative disorders.

PMID- 12803775
TI  - Involvement of inwardly rectifying K+ channels in secretory responses of human
      ileal mucosa.
AB  - In acute secretory diarrhoea the primary event driving fluid secretion is a
      transcellular, electrogenic, serosal to mucosal transport of chloride ions. Such
      transport requires the maintenance of an electrically negative cell membrane
      voltage, which is achieved through a basolateral outward leakage of potassium
      ions. The aim of this study was to investigate the nature of K(+) channel
      involvement in facilitating secretory processes in the human ileum. Muscle
      stripped mucosal preparations of human ileal mucosa were set up in Ussing
      chambers for recording short-circuit current and transmucosal conductance.
      Escherichia coli heat-stable toxin and vasoactive intestinal peptide (VIP)
      produced concentration-dependent increases in short-circuit current. Responses to
      the heat-stable toxin were unaffected by basolateral application of 4
      aminopyridine (5 mM), glibenclamide (10 microM) or a combination of charybdotoxin
      (0.3 microM) plus apamin (0.3 microM). However, basolateral barium (0.2-5 mM)
      caused a concentration-dependent inhibition. Responses to VIP were similarly
      affected by barium (0.05-1 mM). These results suggested that electrogenic
      chloride transport by human ileal mucosa required the presence of basolateral
      K(+) channels. The use of selective K(+)-channel inhibitors and low
      concentrations of barium suggested that the channels involved might be of the
      inwardly rectifying type.

PMID- 12803776
TI  - Pharmacological characterization of MP349, a novel 5-HT1A-receptor antagonist
      with anxiolytic-like activity, in mice and rats.
AB  - The purpose of this study was to further characterize the pharmacological effects
      of MP349 (trans-1-(2-methoxyphenyl)-4-(4-succinimidocyclohexyl)piperazine), a new
      serotonin 5-HT(1A) postsynaptic receptor antagonist, using several biochemical
      and behavioural assays. The silent 5-HT(1A)-receptor antagonist WAY 100635 (N-[2
      [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide)
      was used as a reference compound in in-vivo tests, and diazepam served as
      standard anxiolytic drug in animal models of anxiety. In this study we showed
      that MP349 bound with moderate affinity (K(i) = 234 nM) for alpha(1)
      adrenoceptors, and with very low affinity (K(i) > 2600 nM) for 5-HT(2A), dopamine
      D(1), D(2) and benzodiazepine receptors. The effects of MP349 on presynaptic 5
      HT(1A) receptors were studied in two models (mice and rats). Like WAY 100635,
      MP349 antagonized the hypothermia induced by the 5-HT(1A)-receptor agonist 8
      hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT) in mice. Neither MP349 nor WAY
      100635 administered alone induced hypothermia. In a rat microdialysis study,
      MP349 (like WAY 100635) did not affect 5-HT dialysate level in the prefrontal
      cortex; however, when given before 8-OH-DPAT, it inhibited the decrease in 5-HT
      release induced by the 5-HT(1A )agonist. The data demonstrated that MP349 behaved
      like a functional antagonist of presynaptic 5-HT(1A) receptors. The potential
      anxiolytic activity of MP349 and reference drugs was examined in a conflict
      drinking test in rats, a plus-maze test in rats and a four-plate test in mice.
      MP349 and WAY 100635 produced anxiolytic-like effects, though somewhat weaker
      than those induced by diazepam, and only in the case of diazepam the anxiolytic
      like effects were dose-dependent. Moreover, MP349 administered in doses inducing
      anxiolytic-like effects did not disturb the locomotor activity (open field test)
      or locomotor coordination (rota-rod test) of rats. These and earlier results
      indicated that MP349 was an antagonist of 5-HT(1A) receptors which exhibited
      anxiolytic-like activity in an animal model of anxiety.

PMID- 12803777
TI  - Thiomersal enhances the binding of histamine to the H1 receptor, but not
      histamine-stimulated inositol phosphate formation.
AB  - Thiomersal (thimerosal) was a weak inhibitor of the binding of [(3)H]mepyramine
      to histamine H(1) receptors in guinea-pig cerebellar membranes (11 +/- 1%
      inhibition at 10 microM, 32 +/- 3% inhibition at 300 microM). However, in the
      concentration range 3-30 microM, thiomersal enhanced the binding of histamine to
      the H(1) receptor, as reflected by the displacement of curves of histamine
      inhibition of [(3)H]mepyramine binding to lower concentrations, without any
      change in the Hill coefficient. The ratio of the IC50 values (the concentration
      giving 50% inhibition) in the absence and presence of thiomersal increased from
      1.8 with 3 microM to 3.6 with 30 microM thiomersal. There was no consistent
      effect of thiomersal at concentrations of 30 microM and below on curves of
      mepyramine inhibition of [(3)H]mepyramine binding. In the presence of 10 microM
      thiomersal histamine-induced accumulation of inositol phosphates in U373 MG
      astrocytoma cells was partially inhibited (37 +/- 8% inhibition of the maximum
      response), without any significant change in the EC50 (the concentration giving
      the half maximal response) for histamine. Thus although histamine binding was
      potentiated by thiomersal, there was no potentiation of an H(1) receptor-mediated
      functional response.

PMID- 12803778
TI  - Protective effect of Artemisia douglasiana Besser extracts in gastric mucosal
      injury.
AB  - The aim of this work was to evaluate markers of oxidative stress in ethanol
      induced gastric ulcers and the protective antioxidant activity in-vivo of
      Artemisia douglasiana Besser extracts in ethanol-treated rats. Ethanol-induced
      oxidative damage is believed to be associated with generation of reactive oxygen
      molecules, which leads to oxidative stress. A. douglasiana is used in folk
      medicine as a cytoprotective agent against peptic ulcer. Different bioassays were
      performed: in-vivo stomach chemiluminescence, tert-butyl hydroperoxide initiated
      chemiluminescence (in-vitro chemiluminescence), total antioxidant capacity (TRAP)
      and catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      activity in stomach homogenates. When ethanol (3 g kg(-1)) was administered, the
      in-vivo chemiluminescence increased by 107%, in-vitro chemiluminescence by 108%,
      SOD by 130% (P < 0.001), and catalase and TRAP decreased by 43 and 59% (P < 0.05
      and 0.001, respectively). A. douglasiana (400 mg kg(-1)) pretreatment decreased
      in-vivo chemiluminescence by 41% (P < 0.05), in-vitro chemiluminescence by 66% (P
      < 0.001) and SOD by 56% (P < 0.001) and increased catalase by 14% and TRAP by
      168% (P < 0.001, respectively) but GPx activity was not significantly different
      from the ethanol group. These results illustrate the significant antioxidant
      activity of A. douglasiana extract in-vivo and in-vitro.

PMID- 12803779
TI  - In-vitro and in-vivo antibacterial activity evaluation of a polyurethane matrix.
AB  - Various in-vitro and in-vivo methods for evaluation of the duration of
      antibacterial activity were compared using a controlled-release polyurethane
      matrix developed for the prevention of surface bacterial adhesion and growth.
      Cefadroxil was incorporated into this polyurethane matrix by a solvent casting
      method before the matrix was coated with polyurethane in tetrahydrofuran
      solution. The release of cefadroxil from the matrix into distilled water at 37
      degrees C was measured by HPLC. The morphological change of matrices before and
      after release studies was investigated by scanning electron microscopy (SEM). The
      duration of antimicrobial activity of the matrix against Escherichia coli and
      Staphylococcus aureus was evaluated by measuring the diameters of the inhibition
      zone and the optical density of the broth. The matrices were also implanted
      subcutaneously in rats and the duration of the antibacterial activity was
      determined by measuring the inhibition zone. The results showed that duration of
      antibacterial activity of the polyurethane matrix was successfully determined in
      vitro by these methods, and the results differed from the conventional in-vitro
      release study. It was also possible to determine the duration of action of the
      matrix in-vivo by implanting the matrix in rats, and then measuring the
      antibacterial activity of the matrix at predetermined time intervals. While a
      good correlation was observed between the in-vitro and in-vivo methods used in
      this study to evaluate the duration of the antibacterial activity of the
      polymeric matrix, the conventional in-vitro release study did not coincide with
      these results.

PMID- 12803781
TI  - The Royal National Throat, Nose and Ear Hospital in World War II: a reminiscence.
AB  - The author describes his personal reminiscences of the Royal National, Throat,
      Nose and Ear Hospital during World War II. Many of the colourful characters of
      this era are discussed.

PMID- 12803780
TI  - Three-dimensional computer-aided endoscopic sinus surgery.
AB  - Three-dimensional computer-aided surgery adds a 'third-dimension' to endoscopic
      sinus surgery. The images it provides have the potential to provide the surgeon
      with further information that might result in safer and more effective surgery
      with less surgical morbidity. The gold test, as yet untested, will be whether the
      technique leads to fewer revision procedures and complications as a result of
      more complete and safe initial surgery. Its greatest asset lies in reinforcing
      the surgeons' estimate of an instrument's position in a difficult anatomical
      area. It can augment the learning curve and enhance teaching and training in
      endoscopic sinus surgery but it is not a substitute for a thorough knowledge of
      paranasal sinus anatomy.

PMID- 12803782
TI  - Surgical intervention in middle-ear cholesterol granuloma.
AB  - Eleven patients who had been surgically treated from 1988 to 1999 were
      retrospectively reviewed in order to evaluate the efficacy of ventilation tube
      insertion and mastoidectomy with, or without, mastoid obliteration for
      intractable middle-ear cholesterol granuloma. The mean age registered was 17.2
      years at the time of surgical treatment. All cases were unilaterally affected.
      Five ears were treated with simple mastoidectomy coupled with the insertion of a
      ventilation tube, while six others had additional mastoid obliteration. The
      hearing prognosis was excellent with an improved post-operative hearing level of
      16.5 dB (cf. pre-operative 37.7 dB). However, morphological prognosis revealed
      two ears had a residual perforated tympanic membrane without otorrhoea after
      displacement of the ventilation tube. Of the remaining nine ears with intact
      placement of the ventilation tube, five had dry ears while four had occasional
      otorrhoea. Although the morphological prognosis was incomplete, treatments
      involving at least an insertion of a ventilation tube with thorough mastoidectomy
      were thought to be necessary.

PMID- 12803783
TI  - Transmission of heat to the vestibule during revision stapes surgery using a KTP
      laser: an in vitro study.
AB  - The transmission of heat to the vestibule during revision stapes surgery with a
      piston in situ has been studied using a KTP laser in an in vitro model. A type K
      thermocouple was placed around the medial of each piston tested in a 'vestibule'
      filled with saline. The effect of laser hits on fluoroplastic, fluoroplastic-wire
      and stainless steel stapes prostheses was investigated. The effect of adding
      blood to the operative field, of introducing a vein graft to seal the stapedotomy
      and of vaporizing soft tissue in the oval window were also examined. Greater
      temperature rises occurred with stainless steel than with the other piston types
      and smaller rises occurred when there was a vein graft in situ. The maximum
      temperature rise recorded was 2.6 degrees C. We conclude that the use of the KTP
      laser to clear soft tissue from the oval window is safe when operated at the
      power levels recommended by the manufacturer.

PMID- 12803784
TI  - Labyrinthine fistula: a complication of chronic suppurative otitis media.
AB  - A labyrinthine fistula is a frequent complication of long-standing unsafe chronic
      suppurative otitis media. It is characterized by a slowly progressive erosion of
      the bony labyrinth. In this paper we present our observations regarding the
      diagnosis and management in 50 patients with unsafe chronic suppurative otitis
      media with labyrinthine fistula.

PMID- 12803785
TI  - Posture changes in diabetes mellitus.
AB  - The weight distribution and postural sway was measured in diabetic subjects with,
      and without, neuropathy, and then compared with age and sex matched non-diabetic
      subjects using a cheap and highly portable sway plate - SwayWeigh. The SwayWeigh
      was found to be very practical and the results obtained confirmed the increased
      postural sway in the absence of proprioceptive information in neuropathy
      subjects. The study shows that peripheral neuropathy increases the postural sway
      especially in the absence of visual clues but this did not result in postural
      strategies causing significant limb load asymmetry.

PMID- 12803786
TI  - A new and simple modification of the prosthetic voice restoration technique.
AB  - Several problems have been observed when performing the classic endoscopic
      technique for voice restoration following laryngectomy. An easy and safe method
      is described for the insertion of a Provox voice prosthesis using a Yankauer
      tonsil suction tube and an antrum trocar with an irrigation cannula.

PMID- 12803787
TI  - An evaluation of functional outcomes (speech, swallowing) in patients attending
      speech pathology after head and neck cancer treatment(s): results and analysis at
      12 months post-intervention.
AB  - We have earlier reported establishing a computerized database to audit functional
      outcomes in patients who underwent head and neck cancer treatment in Victoria,
      Australia and attended speech pathology services from April 1997-April 1999. This
      paper presents the statistical analyses and results from this study. Speech
      pathologists collected, prospectively, functional outcome data on 293 patients
      who underwent head and neck cancer treatment, and sent these for analysis to La
      Trobe University. Clinician and patient assessments of outcomes: speech,
      swallowing, activity, pain, employment, health, QOL status were made. Initial
      data on 293 patients were collected and data on mortality and morbidity were
      compiled at three, six and 12 months post-treatment. Within twelve months, 74
      patients had died. Three, six and/or 12-month follow-up data was available on 219
      patients, with both clinician and patient assessments of status completed. The
      status forms are presented as appendices to this paper. Complete status forms on
      179 patients at 12 months were obtained. This clinical audit of functional
      outcomes represents the first study of this kind, collecting data from speech
      pathologists and patients in a multi-centre study of patients with head and neck
      cancer. We present data to demonstrate optimal recovery of function at six
      months, such that this may represent a good reference point for reporting and
      comparison of functional outcomes.

PMID- 12803789
TI  - The comparison of an empiric proton pump inhibitor trial vs 24-hour double-probe
      Ph monitoring in laryngopharyngeal reflux.
AB  - Laryngopharyngeal reflux (LPR), which is defined as the backflow of gastric
      contents into the upper aerodigestive tract, is a relatively common disorder.
      However, its diagnosis still poses many problems. Twenty-four-hour double-probe
      pH monitoring is currently the diagnostic test of choice, but it has many
      disadvantages. Thus, an empiric trial of antireflux therapy has been suggested as
      an alternative method for diagnosis. The purpose of this article is to evaluate
      the validity of this alternative method in the management of LPR. The study group
      consisted of 36 patients with symptoms and physical findings suggesting LPR. The
      control subjects were 23 healthy adults. Twenty-four-hour double-probe pH
      monitoring was performed both in the study group and the control group, and the
      results were compared. In addition, the symptoms and physical findings in the
      study group was scored by the modified reflux symptom index (MRSI) and reflux
      finding score (RFS) at four intervals: before the start of therapy and at the
      second, fourth and sixth months of the therapy. The results of the 24-hour double
      probe pH monitoring showed no significant difference between the study and the
      control groups (p>0.05). In the study group, the MRSI before the therapy was
      13.6+/-4.4. This index improved significantly to 4.3+/-1.9 at the second month;
      to 1.5+/-0.6 at the fourth month, and to 0.5+/-0.2 at the sixth month of the
      therapy (p<0.05). The RFS before the start of the therapy was 14.8+/-3.8; and it
      improved significantly to 7.7+/-3.8 at the second month; to 4.5+/-2.3 at the
      fourth month, and to 1.4+/-0.9 at the sixth month of the therapy (p<0.05). The
      significant improvement in the MRSI and the RFS during the course of proton pump
      inhibitor therapy relates the patients' symptoms and physical findings to LPR.
      This implies the validity of the method, not only in the treatment of LPR, but in
      the diagnosis of this disorder, as well. Unfortunately, 24-hour double-probe pH
      monitoring has failed to differentiate LPR patients from healthy individuals.

PMID- 12803790
TI  - Repair of anterior floor of mouth defects by a central or paramedian island
      tongue flap.
AB  - One method for restoring the anterior floor of mouth defects resulting from T(1)
      and especially T(2) cancer excision involves the creation of a myomucosal island
      flap from the dorsal median portion of the tongue and transferring it as a
      transit flap to the floor of the mouth. We are not the first to advocate this
      method. In this paper we present a previously unreported, slightly modified
      technique utilizing this tongue flap. The modification consists of a 90 degrees
      twisting of the flap to achieve a more appropriate adaptation to the defect. In
      the case of spreading carcinoma from the floor of the mouth to the central
      portion of the tongue, a similar paramedian one-sided tongue flap was created
      instead of a central island tongue flap. Our present experience consists of a
      small series of 12 patients. The procedures were successful in all patients. No
      remarkable disturbances of speech or deglutition were observed in any of the
      patients. There were two complications: one haematoma and one partial necrosis of
      the tip of the tongue. In our opinion, the reconstruction of the anterior floor
      of mouth defects using a central island tongue flap has not gained the popularity
      it deserves.

PMID- 12803791
TI  - Occult bronchogenic carcinoma presenting as metastasis to the site of a bone
      anchored hearing aid.
AB  - The first report of a patient with metastatic bronchogenic carcinoma of the skin
      surrounding the abutment of a bone anchored hearing aid (BAHA) is presented.
      Complications of bone anchored hearing implantation have been well documented to
      date. We present a 68-year-old lady who presented with an unusual skin lesion
      surrounding the abutment of her BAHA. This was the first presentation of her
      bronchogenic tumour. We also review the literature regarding cutaneous metastasis
      and complications of BAHA.

PMID- 12803788
TI  - Is the routine use of antibiotics justified in adult tonsillectomy?
AB  - Pain and secondary haemorrhage are the commonest complications of adult
      tonsillectomy, occurring mostly in the community. This is a randomized, double
      blind, placebo-controlled, prospective trial of the effect of perioperative
      amoxycillin on these complications. The incidence and severity of post-operative
      haemorrhage was measured. For the first 10 post-operative days patients provided
      a linear pain score, a record of GP visits, and their use of additional
      antibiotics and analgesics. Of 95 patients considered: 23 suffered a secondary
      haemorrhage; 54 consulted their general practitioner (GP) because of pain;
      additional antibiotics were used by at least 31 and additional analgesics by at
      least 41. No significant differences were demonstrated between the active and
      placebo groups for any of these measures. This study demonstrates that secondary
      haemorrhage is common after adult tonsillectomy. Post-operative pain remains a
      major problem requiring frequent GP consultations. There appears to be no
      justification for the routine use of perioperative antibiotics.

PMID- 12803792
TI  - Bilateral sudden sensorineural hearing loss caused by Charcot-Marie-Tooth
      disease.
AB  - Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy
      (HMSN) is a relatively common neurological syndrome, which has seldom been
      associated with hearing dysfunction, particularly sudden sensorineural hearing
      loss (SNHL). Families with autosomal dominant, autosomal recessive and X-linked
      forms of inheritance have been described. Sudden sensorineural hearing loss is a
      frustrating and frightening condition, especially if the hearing loss is
      bilateral. Regarding the site of the lesion, the evidence from the literature on
      HMSN suggests that either the VIIIth nerve or central auditory pathways are
      primarily involved in patients with hearing loss. We report the first case in the
      English literature of a patient with Charcot-Marie-Tooth type II disease
      presenting bilateral SNHL in the course of his disease. The patient was
      hospitalized for 15 days, and undergoing treatment without any audiological
      improvement. Detailed clinical, audiological and laboratory examination was
      performed. The aetiology and prognostic indicators of bilateral SNHL are
      discussed, as well as, the incidence of hearing loss in CMT patients.

PMID- 12803793
TI  - Maxillary sinus mucocele presenting as a late complication of a maxillary
      advancement procedure.
AB  - Paranasal sinus mucoceles are benign, locally expansile cyst-like masses that are
      filled with mucus and lined with epithelium. Less than one per cent of them
      involve the maxillary sinus. Most of these are late complications of a Caldwell
      Luc procedure. A case is presented of a 31-year-old woman with a maxillary sinus
      mucocele who had undergone a Le Fort I maxillary advancement procedure 15 years
      previously - a complication never previously reported.

PMID- 12803794
TI  - Primary sinonasal non-Hodgkin's lymphoma masquerading as chronic rhinosinusitis:
      an issue of routine histopathological examination.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the sinonasal tract is uncommon.
      Morphologically and radiographically, sinonasal lymphomas are difficult to
      distinguish from other malignant neoplasms or non-neoplastic processes. However,
      there is no general consensus about the need of routine histopathological
      examination for nasal polyps among otolaryngologists. We present a case of
      primary sinonasal NHL mimicking chronic rhinosinusitis and debate the issue of
      routine histopathological examination. We suggest that all tissues removed from
      the sinonasal tract during surgery must be submitted for histopathological
      examination. Failure to do so may miss diagnosis and delay appropriate treatment.

PMID- 12803795
TI  - Focal mucinosis: clinical and histological features of an unusual condition.
AB  - Mucinoses constitute a diverse group of disorders that have in common the
      deposition of basophilic, finely granular and stringy material in the connective
      tissues of the dermis (known as dermal mucinoses); this also can occur in the
      hair follicles (follicular mucinoses) and finally in the epidermis (epithelial
      mucinoses). We present the clinical and histological findings of a case of focal
      mucinosis in a 76-year-old man who was otherwise fit and healthy. A literature
      review revealed a sparse number of such cases none of which was reported in the
      ENT literature. Focal cutaneous mucinosis is a benign condition but the authors
      believe it is of local and systemic interest to the Otolaryngologist as an
      addition to his or her armentarium of diagnoses.

PMID- 12803796
TI  - Eosinophilic angiocentric fibrosis.
AB  - Eosinophilic angiocentric fibrosis of the upper respiratory tract is a rare
      disorder of unknown aetiology. Despite characteristic histological findings, the
      aetiology and management of this lesion remain unclear. We describe a case of
      nasal eosinophilic angiocentric fibrosis and discuss possible demographic and
      aetiological patterns.

PMID- 12803797
TI  - Bilateral vocal fold palsy caused by chronic motor axonal neuropathy.
AB  - The authors report a first case of chronic motor axonal neuropathy involving ENT
      manifestations, in a 64-year-old male presenting with gait difficulties, effort
      dyspnoea and dysphonia. Eleven months after the first symptoms, he developed
      severe hypoventilation, limb weakness and bilateral vocal fold palsy and had to
      be intubated for respiratory failure. The diagnosis of chronic motor axonal
      neuropathy was suspected on clinical and electrophysiological grounds. The
      patient improved dramatically after a five-day course of 0.4 g/kg intravenous
      immunoglobulin. He is still being treated with methylprednisolone 0.5 mg/kg every
      other day and remains stable. We conclude the bilateral vocal fold palsy may be
      associated with chronic motor axonal neuropathy and that the immunosuppressive
      treatment may be effective in such cases.

PMID- 12803798
TI  - Disseminated septicaemic melioidosis: an unusual presentation of masticator space
      infection.
AB  - Melioidosis is an infectious disease caused by a saprophytic bacterium,
      Burkholderia pseudomallei. It is endemic to Southeast Asia and Northern
      Australia. The spectrum of melioidosis in humans varies from sub-clinical to
      overwhelming protean manifestations resembling other acute and chronic bacterial
      infections. Disseminated septicaemia melioidosis presenting as a masticator space
      infection is reported here. This is germane to those treating diabetic patients
      with deep neck infections living in, or having visited, areas endemic for B.
      pseudomallei.

PMID- 12803800
TI  - Trans-mastoid needle aspiration for otogenic brain abscesses.

PMID- 12803799
TI  - Synchronous bilateral mucoepidermoid carcinoma of the parotid gland.
AB  - It is rare for a parotid gland tumour to arise bilaterally, the most common
      example being Warthin's tumour. Furthermore, it is rare for a parotid gland
      cancer to occur bilaterally. Here, we describe a case of synchronous bilateral
      mucoepidermoid carcinoma arising in the parotid gland. A case of bilateral facial
      nerve dysfunction is presented in which aggressive surgery failed to save the
      life of a 48-year-old man. This is the first such case reported in the available
      English literature.

PMID- 12803801
TI  - Study of the interaction of structurally similar bioactive compounds by thin
      layer chromatography.
AB  - The interaction between steroids and cholesterol is studied by reversed-phase
      thin-layer chromatography (TLC) using TLC plates impregnated by cholesterol and
      methanol-water mixtures as the eluents. The R(M) values obtained are in linear
      correlation with the methanol concentration of the eluent. The slope obtained
      from the linear regression analysis, which is characteristic of the strength of
      interaction, is determined. Stepwise regression and principal component analysis
      are carried out to find a relationship between the physicochemical parameters of
      steroid drugs and the strength of the interaction, which is followed by nonlinear
      mapping and cluster analysis to visualize the obtained results. The results show
      that steric and electronic parameters of the steroid drugs have a significant
      effect on the strength of the interaction between these structurally similar
      molecules.

PMID- 12803802
TI  - Determination of antibacterial flomoxef in serum by capillary electrophoresis.
AB  - A determination method of flomoxef (FMOX) concentration in serum by capillary
      electrophoresis is developed. Serum samples are extracted with acetonitrile.
      After pretreatment, they are separated in a fused-silica capillary tube with a 25
      mM borate buffer (pH 10.0) as a running buffer that contains 50mM sodium dodecyl
      sulfate. The FMOX and acetaminophen (internal standard) are detected by UV
      absorbance at 200 nm. Linearity (0-200 mg/L) is good, and the minimum limit of
      detection is 1.0 mg/L (S/N = 3). The relative standard deviations of intra- and
      interassay variability are 1.60-4.78% and 2.10-3.31%, respectively, and the
      recovery rate is 84-98%. This method can be used for determination of FMOX
      concentration in serum.

PMID- 12803803
TI  - HPLC analysis of metabolically produced formaldehyde.
AB  - Radiolabelled (-)-deprenyl is orally administered to rats, and urinary
      elimination of radiolabelled formaldehyde is detected. The separation is
      performed using high-performance liquid chromatography on octadecyl-silica
      stationary phase. Both the radioactivity and the UV absorbance of the
      dinitrophenylhydrazine formaldehyde peak are determined. Formaldehyde generation
      takes place by N-demethylation. Low levels of formaldehyde may have a beneficial
      role in counterbalancing the oxidative stress of the everyday person's life.

PMID- 12803804
TI  - Capillary electrophoretic behaviors of pharmacologically active xanthones from
      Securidaca inappendiculata with beta-cyclodextrin as a buffer additive.
AB  - The capillary electrophoretic (CE) behaviors of ten xanthones in the presence of
      beta-cyclodextrin (CD) are investigated, and apparent analyte-selector binding
      constants between beta-CD and the xanthones in the CE running buffer are
      calculated to elucidate the migration order. Also, the separation selectivity
      with beta-CD additive is compared with that of sulfated beta-CD additive. It is
      indicated that beta-CD can greatly change the separation selectivity of
      xanthones, and the electrophoretic behaviors of xanthones are rather different
      when using beta-CD from that when using sulfated beta-CD as an additive.

PMID- 12803805
TI  - Feasibility of enhancing high-performance liquid chromatography using microwave
      radiation.
AB  - High-performance liquid chromatography (HPLC) is the most versatile of the
      chromatographic techniques because it is applicable to a wide variety of
      analytes. Unfortunately, liquid mobile phases have relatively low diffusivities.
      A novel approach is presented for increasing the diffusivity of a liquid mobile
      phase. The method advocated in this study is the first process that has been
      described by which it is possible to increase the diffusivity of a liquid while
      having essentially no effect on other physical properties of the liquid, such as
      the temperature or solvating power. It is demonstrated that it is possible to
      sharpen peaks, in an HPLC separation, by the application of microwave radiation.

PMID- 12803806
TI  - Gas chromatography-mass spectrometry-single ion monitoring measurement of 11-nor
      delta 9-tetrahydrocannabinol-carboxylic acid in urine.
AB  - Gas chromatography combined with mass spectrometry is used to determine the
      urinary elimination of 11-nor-Delta(9)-tetrahydrocannabinol-carboxylic acid.
      Single ion monitoring of both 11-nor-Delta(9)-tetrahydrocannabinol-carboxylic
      acid and the internal standard (11-nor-Delta(9)-tetrahydrocannabinol-carboxylic
      D9) offers selective and sensitive measurement. In order to check the method and
      the results, we employ 11-nor-Delta(9)-tetrahydrocannabinol-carboxylic acid
      glucuronide as an external standard. Our study also demonstrates that the wall of
      the glass liner (glass tube) in the injector retards the active compound, which
      makes it imperative to replace the glass insert after each run. Otherwise, the
      value of the drug measured in subsequent runs will decrease because more of this
      compound will adhere to the glass walls.

PMID- 12803807
TI  - Simultaneous determination of four heavy metal ions in tobacco and tobacco
      additive by online enrichment followed by RP-HPLC and microwave digestion.
AB  - A new method for the simultaneous determination of tin, lead, cadmium, and
      mercury in tobacco and tobacco additive by reversed-phase high-performance liquid
      chromatography combined with microwave digestion and an online enrichment
      technique is developed. The tin, lead, cadmium, and mercury ions are precolumn
      derivatized with tetra-(4-dimethylaminophenyl)-porphyrin (T(4)-DMAPP) to form
      color chelates. The Sn-T(4)-DMAPP, Hg-T(4)-DMAPP, Cd-T(4)-DMAPP, and Pb-T(4)
      DMAPP chelates are absorbed onto the front of the enrichment column using a
      buffer solution of 0.05 mol/L pyrrolidine-acetic acid (pH = 10.0) as the mobile
      phase. After the concentration is finished (by switching the six-port switching
      valve) the retained chelates are back-flushed by the mobile phase and move to the
      analytical column. The chelate separation on the analytical column is
      satisfactory using gradient elution with methanol (containing 0.05 mol/L
      pyrrolidine-acetic acid buffer salt, pH = 10.0) and tetrahydrofuran (containing
      0.05 mol/L pyrrolidine-acetic acid buffer salt, pH = 10.0). The linearity range
      is 0.01-120 micro g/L for each metal ion. The detection limits (S/N = 3) of tin,
      lead, cadmium, and mercury are 0.6, 0.8, 0.5, and 0.6 ng/L, respectively. This
      method is applied to the determination of tin, lead, cadmium, and mercury in
      tobacco and it's additive with good results.

PMID- 12803808
TI  - Photolysis of NSAIDs. I. photodegradation products of carprofen determined by LC
      ESI-MS.
AB  - A solution of carprofen in methanol at a concentration of 2.74 x 10(-2) mg/mL is
      subjected to photoirradiation using a Hanovia 200-W high-pressure Hg lamp for 9
      h. In total, seven photodegradation products are separated, and their
      quasimolecular ions are subsequently determined online using a liquid
      chromatography (LC)-electrospray ionization (ESI)-mass spectrometry (MS) method.
      The high-performance LC consists of an Inertsil 5 ODS-80A (2.1- x 150-mm) column.
      The mobile phase is initially CH(3)CN. NH(4)OAc (20mM in de-ionized H(2)O) is
      43:57 (v/v), and after 14 min it is CH(3)CN. NH(4)OAc (20mM in de-ionized H2O) is
      54: 46 (v/v). The UV detector was set at 260 nm. The parameters of LC-MS for mass
      determination involves an atmospheric pressure ionization electron spray
      interface with a negative mode of polarity (ESI(-)). The chemical structures of
      the degradants are elucidated based on the mass-to-charge ratio of the
      quasimolecular ions and the molecular weight changes by comparison with the
      parent drug (carprofen). The degradation proceeds via an initial dechlorination.
      A dechlorination or esterification reaction is competed with decarboxylation.
      This finding is in accordance with our previously reported result of first order
      photodecomposition kinetics for carprofen.

PMID- 12803809
TI  - GC Behavior of disaccharide trimethylsilyl oximes.
AB  - Twenty-five disaccharides are converted to trimethylsilyl oximes and injected on
      two capillary columns of different polarities (methyl and phenyl-methyl
      silicone). Their Kovats retention indices are determined at three temperatures.
      Multivariate data analysis is used in order to obtain relations between retention
      and some structural features. Phenylmethyl silicone have better chromatographic
      characteristics for the assayed compounds. The two columns can provide useful
      chromatographic information when a very complex disaccharide mixture has to be
      analyzed.

PMID- 12803810
TI  - Fast HPLC with a silica-based monolithic ODS column.
AB  - Fast high-performance liquid chromatography is becoming routine in laboratories
      that require high throughput or for combinatorial libraries. Reduced analysis
      time is commonly achieved by using shorter columns and higher flow rates. Shorter
      columns require smaller particles in order to maintain efficiency. However,
      smaller particles increase backpressure, which limits both column length and
      higher flow rates for typical LC pumps. This disadvantage has been addressed by
      the emergence of monolithic liquid chromatographic columns (1). Unlike particle
      base columns, monolithic columns consist of a continuous rod-shaped porous
      network with a bimodal pore distribution. In this study, a commercially available
      50- x 4.6-mm silica-based octadecyl silane monolithic column (Chromolith SpeedROD
      RP18e, EM Science, Gibbstown, NJ) was used to separate a seven-component test
      mixture with a wide range of polarity. The primary goals of this investigation
      were: (a) to study the chemistry (selectivity) of the new silica-based monolithic
      columns and (b) to study their run-to-run and column-to-column performance
      (retention times and peak areas). The selectivity (alpha factor) is a ratio of
      partition coefficients and, if comparable for a variety of solutes, would mean
      that methods could be readily transferred between particulate and monolithic
      columns.

PMID- 12803811
TI  - Solute-solvent interactions from gas chromatographic activity coefficients and
      the solvation parameter model for nitrogen-containing stationary phases.
AB  - Infinite dilution gas-liquid chromatographic activity coefficients (gamma) and
      excess thermodynamic molar partial magnitudes [Gibbs energy (G(E)), enthalpy
      (H(E)), and entropy (S(E))] for 37 solutes of varied polarity on four stationary
      phases with -NH groups are obtained from partition coefficients taken from
      literature. Relationships between G(E) and S(E) with the 37 solutes' structure in
      terms of the molecular connectivity index ((1)chi(v)) are investigated.
      Correlations of solute-solvent interactions calculated in light of the solvation
      parameter model for selected solutes and stationary phases are tested. The effect
      of the solute's structure, expressed as the molecular connectivity index, on the
      nonpolar (cavity formation and dispersion interaction) [c+l. log L(16)] and the
      effect of the dipole moment and of the activity coefficient on the dipolarity
      polarizability interaction (spi(2)(H)) are studied. The correlation between the
      nonpolar interaction with the athermal activity coefficient on the nonpolymeric
      stationary phases is also attempted. In addition, the influence of the stationary
      phase polarity on the solute-stationary phase interactions for a series of
      solutes is studied.

PMID- 12803812
TI  - Foundation literacy acquisition in European orthographies.
AB  - Several previous studies have suggested that basic decoding skills may develop
      less effectively in English than in some other European orthographies. The
      origins of this effect in the early (foundation) phase of reading acquisition are
      investigated through assessments of letter knowledge, familiar word reading, and
      simple nonword reading in English and 12 other orthographies. The results confirm
      that children from a majority of European countries become accurate and fluent in
      foundation level reading before the end of the first school year. There are some
      exceptions, notably in French, Portuguese, Danish, and, particularly, in English.
      The effects appear not to be attributable to differences in age of starting or
      letter knowledge. It is argued that fundamental linguistic differences in
      syllabic complexity and orthographic depth are responsible. Syllabic complexity
      selectively affects decoding, whereas orthographic depth affects both word
      reading and nonword reading. The rate of development in English is more than
      twice as slow as in the shallow orthographies. It is hypothesized that the deeper
      orthographies induce the implementation of a dual (logographic + alphabetic)
      foundation which takes more than twice as long to establish as the single
      foundation required for the learning of a shallow orthography.

PMID- 12803813
TI  - Victimization in the school and the workplace: are there any links?
AB  - We examine whether reported roles in school bullying, and victimization in the
      workplace, are connected; the influence of victim coping strategies at school;
      and sex differences. A questionnaire was completed by 5,288 adults from various
      workplace venues in Great Britain. We analysed two questions on school
      experiences (participant role; coping strategies if bullied) and questions on
      workplace bullying (experiences of being bullied). We found a significant
      relationship between reported roles in school bullying, and experience of
      workplace victimization. The highest risk of workplace victimization was for
      those who were both bullies and victims at school (bully/victims), followed by
      those who were only victims. An analysis of relative risk of workplace bullying,
      given being a victim at school plus using various coping strategies, revealed an
      increased risk for the strategies 'tried to make fun of it', and 'did not really
      cope'. Women were at slightly higher risk of getting bullied at work, but there
      were no interactions with roles at school, and only one interaction with coping
      strategies. This is the first study to report an association between school and
      workplace bullying. Victims at school are more at risk of workplace
      victimization, but the especial risk for 'bully/victims' supports other
      indications that this particular category of school pupils should be a focus of
      concern. The findings also suggest that school pupils who consistently cannot
      cope with bullying, or try to make fun of the bullying, are more at risk for
      later problems in the workplace. However, associations are modest; many victims
      of school bullying are not being victimized in later life, and the results also
      suggest important contextual or environmental effects on risks of victimization.

PMID- 12803814
TI  - Erroneous verbalizations and risk taking at video lotteries.
AB  - This study examined the effect of erroneous perceptions verbalized by a game
      accomplice on participants' gambling. The sample consisted of 22 men and 10
      women, aged 18 and older, who did not show excessive gambling problems, but who
      had played video lotteries at least once during the last 6 months. The
      participants were randomly assigned into one of three groups, where they gambled
      in the presence of an accomplice who verbalized three types of perceptions: (1)
      the accomplice emitted erroneous thoughts about gambling, (2) the accomplice
      verbalized adequate thoughts about gambling, or (3) the accomplice did not speak.
      Results showed that players exposed to an accomplice's erroneous verbalizations
      took significantly more risks than players in the other two groups. Erroneous
      perceptions appear to be easily transmissible and have impacts on gambling
      behaviour. The practical and theoretical implications of these results are
      discussed.

PMID- 12803815
TI  - An investigation into alleged 'hauntings'.
AB  - In cases of alleged hauntings, a large number of seemingly trustworthy witnesses
      consistently report experiencing unusual phenomena (e.g. apparitions, sudden
      changes in temperature, a strong sense of presence) in certain locations. The two
      studies reported here explored the psychological mechanisms that underlie this
      apparent evidence of 'ghostly' activity. The experiments took place at two
      locations that have a considerable reputation for being haunted-Hampton Court
      Palace (Surrey, England) and the South Bridge Vaults (Edinburgh, Scotland). Both
      studies involved participants walking around these locations and reporting where
      they experienced unusual phenomena. Results revealed significantly more reports
      of unusual experiences in areas that had a reputation for being haunted. This
      effect was not related to participants' prior knowledge about the reputation of
      these areas. However, the location of participants' experiences correlated
      significantly with various environmental factors, including, for example, the
      variance of local magnetic fields and lighting levels. These findings strongly
      suggest that alleged hauntings may not necessarily represent evidence for
      'ghostly' activity, but could be, at least in part, the result of people
      responding to 'normal' factors in their surroundings.

PMID- 12803816
TI  - Mental undoing of actions and inactions in the absence of counterfactuals.
AB  - Three studies investigated the emotional impact of actions and inactions in the
      long term when no counterfactuals were provided. Using the investment scenario,
      Byrne and McEleney (2000) showed that people did not regret inaction more than
      action in the long term when they knew the counterfactuals of both. In the
      present Experiments 1 and 2, it was found that when both counterfactuals were not
      known, people still judged that actions would be regretted more than inactions
      not only in the short term but also in the long term. In Experiment 3, the actor
      and the non-actor were judged separately. As expected, no emotional difference
      was found between them, but the actor was attributed worse feelings in the long
      term than in the short term.

PMID- 12803817
TI  - The effects of morphology on the processing of compound words: evidence from
      naming, lexical decisions and eye fixations.
AB  - The use of lexemes during the recognition of spatially unified familiar English
      compounds was examined in naming, lexical decision and sentence-reading tasks by
      manipulating beginning and ending lexeme frequencies while controlling overall
      compound frequencies. All tasks revealed robust ending lexeme frequency effects,
      with compound processing being more effective when the ending lexeme was a high
      frequency word. Beginning lexeme frequency effects were more elusive and
      dependent on task demands. Eye movements, recorded during sentence reading, also
      indicated that the effects of ending lexemes occurred after the first fixation
      during compound viewing. Together, the results suggest either that the ending
      lexeme is used as an access code to locate the meaning of the full compound word
      or that its meaning is coactive with the meaning of the full compound.

PMID- 12803818
TI  - The relationship between self-reports of imagery and spatial ability.
AB  - A puzzling question arising from imagery research is why no relationship has been
      found between self-reports of imagery and performance on spatial tests thought to
      require the use of imagery. To investigate this, spatial ability, measured by
      performance on two spatial tests, was compared with performance on the Vividness
      of Visual Imagery Questionnaire (VVIQ; Marks, 1973) and a newly constructed
      imagery questionnaire. The choice of items and ratings for the new questionnaire
      was based on Kosslyn's (1980, 1994) theories of the imagery system. Ratings on
      the new questionnaire consistently correlated significantly with performance on
      the spatial tests, whereas ratings from the VVIQ did not. The new ratings
      captured more of the imagery process than ratings of vividness alone, but the
      largest change depended upon the type of item imagined. Ratings of items of the
      same type as used on the spatial tests predicted performance on the spatial
      tests, whereas vividness ratings of items recalled or constructed from long-term
      memory did not. Participants can successfully introspect on several different
      properties of their images, and their ratings do predict performance on tasks
      thought to require imagery. The large effect of item type raises questions about
      the predictive value of existing models of the imagery system especially in
      relation to the role of phenomenological properties of our images.

PMID- 12803819
TI  - Repeated measures one-way ANOVA based on a modified one-step M-estimator.
AB  - Wilcox, Keselman, Muska and Cribbie (2000) found a method for comparing the
      trimmed means of dependent groups that performed well in simulations, in terms of
      Type I errors, with a sample size as small as 21. Theory and simulations indicate
      that little power is lost under normality when using trimmed means rather than
      untrimmed means, and trimmed means can result in substantially higher power when
      sampling from a heavy-tailed distribution. However, trimmed means suffer from two
      practical concerns described in this paper. Replacing trimmed means with a robust
      M-estimator addresses these concerns, but control over the probability of a Type
      I error can be unsatisfactory when the sample size is small. Methods based on a
      simple modification of a one-step M-estimator that address the problems with
      trimmed means are examined. Several omnibus tests are compared, one of which
      performed well in simulations, even with a sample size of 11.

PMID- 12803820
TI  - Dynamical system approach to factor analysis parameter estimation.
AB  - A new unified approach to solving and studying the factor analysis parameter
      estimation problem is proposed. The maximum likelihood and least squares
      formulations of factor analysis are considered. The approach leads to globally
      convergent procedures for simultaneous estimation of the factor analysis
      parameters. The method presented necessarily leads to proper factor analysis
      estimations.

PMID- 12803821
TI  - A method of moments technique for fitting interaction effects in structural
      equation models.
AB  - The desire to fit structural equation models containing an interaction term has
      received much methodological attention in the social science literature. This
      paper presents a technique for the cross-product structural model that utilizes
      factor score estimates and results in closed-form moments-type estimators. The
      technique, which does not require normality for the underlying factors, was
      originally introduced in a very general form by Wall and Amemiya (2000) for any
      polynomial structural model. In this paper, the practical implementation of this
      method, including standard error estimation, is presented specifically for the
      cross-product model. The procedure is applied to an example from
      social/behavioural epidemiology where the flexibility of the cross-product model
      provides a useful description of the underlying theory. A simulation study is
      also presented comparing the method of moments for the cross-product model with
      three other procedures.

PMID- 12803822
TI  - Stochastic EM for estimating the parameters of a multilevel IRT model.
AB  - An item response theory (IRT) model is used as a measurement error model for the
      dependent variable of a multilevel model. The dependent variable is latent but
      can be measured indirectly by using tests or questionnaires. The advantage of
      using latent scores as dependent variables of a multilevel model is that it
      offers the possibility of modelling response variation and measurement error and
      separating the influence of item difficulty and ability level. The two-parameter
      normal ogive model is used for the IRT model. It is shown that the stochastic EM
      algorithm can be used to estimate the parameters which are close to the maximum
      likelihood estimates. This algorithm is easily implemented. The estimation
      procedure will be compared to an implementation of the Gibbs sampler in a
      Bayesian framework. Examples using real data are given.

PMID- 12803823
TI  - An enhanced branch-and-bound algorithm for a partitioning problem.
AB  - This paper focuses on the problem of developing a partition of n objects based on
      the information in a symmetric, non-negative dissimilarity matrix. The goal is to
      partition the objects into a set of non-overlapping subsets with the objective of
      minimizing the sum of the within-subset dissimilarities. Optimal solutions to
      this problem can be obtained using dynamic programming, branch-and-bound and
      other mathematical programming methods. An improved branch-and-bound algorithm is
      shown to be particularly efficient. The improvements include better upper bounds
      that are obtained via a fast exchange algorithm and, more importantly, sharper
      lower bounds obtained through sequential solution of submatrices. A modified
      version of the branch-and-bound algorithm for minimizing the diameter of a
      partition is also presented. Computational results for both synthetic and
      empirical dissimilarity matrices reveal the effectiveness of the branch-and-bound
      methodology.

PMID- 12803824
TI  - Bootstrap approach to inference and power analysis based on three test statistics
      for covariance structure models.
AB  - We study several aspects of bootstrap inference for covariance structure models
      based on three test statistics, including Type I error, power and sample-size
      determination. Specifically, we discuss conditions for a test statistic to
      achieve a more accurate level of Type I error, both in theory and in practice.
      Details on power analysis and sample-size determination are given. For data sets
      with heavy tails, we propose applying a bootstrap methodology to a transformed
      sample by a downweighting procedure. One of the key conditions for safe bootstrap
      inference is generally satisfied by the transformed sample but may not be
      satisfied by the original sample with heavy tails. Several data sets illustrate
      that, by combining downweighting and bootstrapping, a researcher may find a
      nearly optimal procedure for evaluating various aspects of covariance structure
      models. A rule for handling non-convergence problems in bootstrap replications is
      proposed.

PMID- 12803825
TI  - An asymptotic partial correlation test for the Goodman-Kruskal lambda.
AB  - Goodman and Kruskal introduced a measure of predictive association when
      predicting the category of a variable A from a category of a variable B. This
      measure, denoted lambda, is the asymmetric proportional reduction in error
      measure in predicting an individual's A category that can be eliminated by using
      knowledge of the B classification. It takes values on the unit interval, with a
      zero value meaning no predictive gain, while a value of unity indicates a perfect
      predictive association between A and B. A test of H(0): lambda = 0 versus H(1):
      lambda > 0 is analogous to a test for the significance of the correlation
      coefficient. A test of the partial lambda coefficient, which is analogous to a
      test of the partial correlation coefficient, answers the question of whether
      knowledge of an additional third (or higher) classification or categorical
      variable results in a significant increase in predicting the variable A. Suich
      and Turek developed an exact test for the partial lambda coefficient, but only
      for the situation where the predicted categorical variable A is dichotomous. The
      present paper completes the previous work by developing an asymptotic test where
      the predicted category A is any polytomous variable.

PMID- 12803826
TI  - A fast method for choosing the numbers of components in Tucker3 analysis.
AB  - Recently, Timmerman and Kiers proposed an effective procedure for choosing the
      numbers of components in Tucker3 analysis, a kind of component analysis of three
      way data. The procedure, however, is rather time-consuming, relying on very many
      complete Tucker3 analyses. Here, an alternative procedure is proposed, which
      basically relies on a single, quick analysis of the three-way data set. In a
      simulation study it was found that the new procedure is comparable in its effect
      to the original procedure.

PMID- 12803827
TI  - Evaluation of global testing procedures for item fit to the Rasch model.
AB  - Two types of global testing procedures for item fit to the Rasch model were
      evaluated using simulation studies. The first type incorporates three tests based
      on first-order statistics: van den Wollenberg's Q(1) test, Glas's R(1) test, and
      Andersen's LR test. The second type incorporates three tests based on second
      order statistics: van den Wollenberg's Q(2) test, Glas's R(2) test, and a non
      parametric test proposed by Ponocny. The Type I error rates and the power against
      the violation of parallel item response curves, unidimensionality and local
      independence were analysed in relation to sample size and test length. In
      general, the outcomes indicate a satisfactory performance of all tests, except
      the Q(2) test which exhibits an inflated Type I error rate. Further, it was found
      that both types of tests have power against all three types of model violation. A
      possible explanation is the interdependencies among the assumptions underlying
      the model.

PMID- 12803828
TI  - Bayesian model selection for mixtures of structural equation models with an
      unknown number of components.
AB  - This paper considers mixtures of structural equation models with an unknown
      number of components. A Bayesian model selection approach is developed based on
      the Bayes factor. A procedure for computing the Bayes factor is developed via
      path sampling, which has a number of nice features. The key idea is to construct
      a continuous path linking the competing models; then the Bayes factor can be
      estimated efficiently via grids in [0, 1] and simulated observations that are
      generated by the Gibbs sampler from the posterior distribution. Bayesian
      estimates of the structural parameters, latent variables, as well as other
      statistics can be produced as by-products. The properties and merits of the
      proposed procedure are discussed and illustrated by means of a simulation study
      and a real example.

PMID- 12803829
TI  - Pairwise multiple comparisons: a model comparison approach versus stepwise
      procedures.
AB  - Researchers in the behavioural sciences have been presented with a host of
      pairwise multiple comparison procedures that attempt to obtain an optimal
      combination of Type I error control, power, and ease of application. However,
      these procedures share one important limitation: intransitive decisions.
      Moreover, they can be characterized as a piecemeal approach to the problem rather
      than a holistic approach. Dayton has recently proposed a new approach to pairwise
      multiple comparisons testing that eliminates intransitivity through a model
      selection procedure. The present study compared the model selection approach (and
      a protected version) with three powerful and easy-to-use stepwise multiple
      comparison procedures in terms of the proportion of times that the procedure
      identified the true pattern of differences among a set of means across several
      one-way layouts. The protected version of the model selection approach selected
      the true model a significantly greater proportion of times than the stepwise
      procedures and, in most cases, was not affected by variance heterogeneity and non
      normality.

PMID- 12803831
TI  - Ubiquinone: cholesterol's reclusive cousin.
AB  - Coenzyme Q(10) (CoQ(10)) is the predominant form of ubiquinone in man. CoQ(10)
      functions as an electron carrier in the mitochondrial respiratory chain as well
      as serving as an important intracellular antioxidant. Lowered blood and tissue
      concentrations of CoQ(10) have been reported in a number of diseases, although
      whether this deficiency is the cause or an effect of the disease remains largely
      unresolved. Some studies have reported lowered plasma CoQ(10) concentrations
      after statin drug treatment of hypercholesterolaemic patients. However, a
      deficiency in CoQ(10) status has yet to be demonstrated in patients experiencing
      the rare myotoxic side-effects of these drugs. Most clinical investigations
      assessing the therapeutic potential of CoQ(10) have focused on cardiovascular
      disease, specifically congestive heart failure. Although a number of studies have
      reported clinical improvement in congestive heart failure patients after CoQ(10)
      supplementation to standard therapy, concerns about the design of these studies
      coupled to the small number of patients involved have limited their acceptance.
      Assessment of CoQ(10) status is generally based on plasma measurements. As plasma
      concentrations are influenced by a number of physiological factors and may not
      represent cellular concentrations, platelets, lymphocytes and fibroblasts may
      provide suitable alternatives for these measurements.

PMID- 12803832
TI  - The effect of temporal variation in biochemical markers of trisomy 21 across the
      first and second trimesters of pregnancy on the estimation of individual patient
      specific risks and detection rates for Down's syndrome.
AB  - BACKGROUND: In a previous study we examined the changes in the median multiple of
      the median (MoM) with gestation of free beta human chorionic gonadotrophin (F
      beta-hCG), total human chorionic gonadotrophin (ThCG), alpha-fetoprotein (AFP)
      and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's
      syndrome pregnancies. Results showed that there was a significant temporal
      variation of the MoM for each marker. In this paper, we assess the impact of this
      temporal shift on the estimation of patient-specific risks and the detection
      rates (DRs) for Down's syndrome pregnancies. METHODS: Individual patient-specific
      risks, DRs and false positive rates were estimated using statistical modelling
      techniques and computer simulations. The data for these simulations were the
      regressed mean log(10) analyte MoMs, marker standard deviations (as log(10) MoM)
      and correlation coefficients derived from the analysis of over 1000 cases of
      Down's syndrome and 150,000 unaffected pregnancies between 6 and 20 weeks of
      gestation reported in our previous study. Two models were compared: the classical
      constant median separation model, which assumes no variation in median shift with
      gestation (model 1), and a variable median separation model (model 2), which
      takes account of the changes in median shift with gestation as described in our
      previous study. RESULTS: When individual patient-specific risks calculated for
      various MoM values using model 1 were compared with those derived from model 2,
      considerable differences in risk estimates were observed for all marker
      combinations, particularly in the first trimester. Using a 1 in 250 cut-off risk,
      DRs at each gestation in the second trimester for the AFP+F beta-hCG combination
      were maximized at 14-17 weeks of gestation and were virtually identical at 63-65%
      for model 1 and model 2. A similar trend was observed for the AFP+ThCG
      combination, with an optimum gestational range of 15-18 weeks and DRs of 66-68%.
      In the first trimester, using a 1 in 250 cut-off risk, DRs were more variable
      with gestation for the prime marker combination of F beta-hCG+PAPP-A, varying
      from 73% at 8 weeks to 65% at 13 weeks with model 1 and from 75% to 66% with
      model 2. CONCLUSION: Risk algorithms should take into account temporal variation
      in marker MoMs in order to produce accurate patient-specific risks. This also
      helps to maximize DRs, particularly when samples are taken out with the optimal
      gestational range.

PMID- 12803834
TI  - Urinary PC-1 activity in patients with type 1 diabetes mellitus.
AB  - BACKGROUND: Insulin resistance characterizes type 1 diabetes mellitus with
      nephropathy. The molecular mechanisms of insulin resistance are not completely
      understood. Recently some advances have been made in identification of
      transmembrane glycoprotein PC-1 as a potential factor of insulin resistance.
      METHODS: We measured urinary excretion of PC-1 (alkaline phosphodiesterase I), a
      potential factor of insulin resistance, and N-acetyl-beta-D-glucosaminidase
      (NAGA) in 62 type 1 diabetic patients with different damage to the kidney.
      RESULTS: In newly detected type 1 diabetes patients, before insulin therapy,
      urine PC-1 excretion was significantly increased (P<0.05) over the control level.
      However, in patients after 12.4 years of therapy, urinary PC-1 was significantly
      decreased (P<0.05). Decreased urine PC-1 activity (P<0.05) was found also in type
      1 diabetes patients with microalbuminuria and manifest nephropathy, including
      those with renal failure. Urinary NAGA excretion was found to be significantly
      increased (P=0.001) in all but the group of type 1 diabetes patients without
      nephropathy. CONCLUSION: This study of urinary PC-1 in patients with type 1
      diabetes shows increased excretion in newly detected patients with poor glycaemic
      control, but decreased excretion in patients with micro-/macroalbuminuria as well
      as in those without apparent kidney damage. In patients with primary
      glomerulonephritis, urinary excretion of PC-1 was significantly decreased and
      that of NAGA significantly increased compared with the excretion in healthy
      controls.

PMID- 12803833
TI  - Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2
      diabetes treated with metformin, gliclazide or glibenclamide.
AB  - BACKGROUND: Insulin resistance is a key feature of type 2 diabetes mellitus.
      Plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor
      tyrosine kinase, and has been implicated in the pathogenesis of insulin
      resistance. METHODS: Urinary excretion of PC-1 was determined in 45 newly
      detected, obese diabetic patients treated with metformin (16 patients),
      gliclazide (14 patients) or glibenclamide (15 patients). Urinary N-acetyl-beta-D
      glucosaminidase (NAGA), a lysosomal enzyme, was determined as a marker of tubular
      damage in diabetes. RESULTS: Basal urinary PC-1 excretion in all three groups of
      diabetic patients was at the level of healthy controls. Treatment with oral
      hypoglycaemic drugs did not change significantly the group level or the number of
      patients in each group with increased PC-1 activity. Urinary excretion of NAGA in
      patients with type 2 diabetes was not statistically different from the control
      level. Metformin and gliclazide treatment did not change significantly the group
      levels of NAGA excretion. However, glibenclamide treatment produced an increased
      urinary NAGA excretion in the whole group, and in about twice as many patients as
      in the pre-treatment period.

PMID- 12803835
TI  - An audit of the laboratory interpretation of growth hormone response to insulin
      induced hypoglycaemia in the assessment of short stature in children.
AB  - INTRODUCTION: Measurement of serum growth hormone (GH) concentration in response
      to insulin-induced hypoglycaemia remains an important investigation in the
      assessment of pituitary disease. METHODS: In this audit, laboratories were
      presented with aliquots of sera with GH concentrations likely to be found in an
      insulin stress test (IST). They were invited to analyse the specimens for GH and
      comment on their results. RESULTS AND DISCUSSION: A number of laboratories
      appeared to be using out-of-consensus cut-off concentrations that sometimes were
      unrelated to the bias of their GH assay. The specimens were chosen to mimic those
      seen in an IST that was clearly not indicative of GH deficiency, so there was
      reasonable consensus in the interpretation of results. However, five laboratories
      (9.6%) did indicate that their results were equivocal.

PMID- 12803836
TI  - Measurement of cardiac troponin I in striated muscle using three experimental
      methods.
AB  - BACKGROUND: Qualitative and quantitative measures of cardiac troponin I (cTnI) in
      striated muscle have been reported as part of diverse investigations. However,
      there is disparity in the literature regarding the findings of these analyses.
      The cTnI molecule can exist in phosphorylated, non-phosphorylated, reduced, non
      reduced, complexed or non-complexed forms. Each of these forms can change the
      antigenicity of cTnI, resulting in different antibody-antigen interactions in
      different experimental formats, thereby giving rise to the disparities in the
      literature. METHODS: cTnI in heart and skeletal muscles were investigated by
      three techniques employing the same specific cTnI antibodies: the recently
      revised Dade-Behring Dimension RXL assay, immunoblotting and
      immunohistochemistry. RESULTS: cTnI was detected in heart muscle but not skeletal
      muscle using the quantitative assay and immunoblotting. Unexpectedly, using the
      same antibodies, cTnI was not immunolocalized to either heart or skeletal muscle.
      CONCLUSION: The antibody-cTnI interaction might be impeded on fixed
      immunohistochemistry sections. Our findings reflect those of a previous study,
      showing that cTnI was not detected in skeletal muscle extracts using a
      quantitative assay. The behaviour of cTnI antibodies varies depending on
      experimental design. Conclusions drawn from experiments using qualitative methods
      cannot necessarily be extrapolated to the quantitative assay and vice versa.

PMID- 12803837
TI  - Interference caused by the contents of serum separator tubes in the Vitros CRP
      assay.
AB  - BACKGROUND: We have observed discrepancies between C-reactive protein (CRP)
      measured in serum prepared from a serum separator tube (SST) and that obtained
      from a plain tube, when using the Vitros CRP assay. Our study aimed at
      elucidating the cause of these discrepancies. METHODS: Eighty-seven specimens
      from hospitalized patients with various types of inflammatory disease were
      analysed using a fixed-point immuno-rate method on a Vitros CRP slide. The serum
      was prepared simultaneously in both vacuum and SSTs. We also performed mixing
      tests by adding 47 samples of serum prepared from plain tubes to SSTs and
      incubating for 15 min before CRP analysis. RESULTS: Lower values of CRP were
      found in serum prepared from plain tubes than in serum from SSTs. Addition of
      serum prepared from plain tubes to SSTs and incubating for 15 min increased the
      CRP values significantly. The ratio of CRP measured in serum prepared from plain
      tubes and from SSTs did not differ significantly from the ratio obtained when
      serum was prepared in a plain tube then added to an SST. DISCUSSION: We propose
      that SSTs can adsorb some macromolecules that form complexes with CRP. The
      addition of SST gel to serum results in the release of CRP molecules from these
      complexes, which enhances the antigen-antibody reaction on the Vitros CRP slide
      and increases the measured CRP concentrations.

PMID- 12803838
TI  - Comparison of perfusate activities of glutathione S-transferase, alanine
      aminopeptidase and fatty acid binding protein in the assessment of non-heart
      beating donor kidneys.
AB  - BACKGROUND: With a universal shortage of donor organs, screening and selection of
      marginal kidneys from non-heart-beating donors (NHBDs) provides a valuable source
      for transplantation. Pre-transplant viability assessment is based on a
      combination of flow characteristics and assessment of ischaemic tissue injury
      during NHBD kidney machine perfusion by measurement of total glutathione S
      transferase (GST) activity. Successful viability screening has facilitated 69
      renal transplants from 60 NHBDs within our transplant centre since 1998, with a
      first-year graft survival of 90.5%. METHODS: We have investigated alanine
      aminopeptidase (Ala-AP) and fatty acid binding protein (FABP) as alternative
      biochemical markers to GST for pre-transplantation viability assessment. They
      were measured, together with GST, in tissue perfusate samples from machine
      perfused kidneys from controlled and uncontrolled NHBDs. RESULTS: During machine
      perfusion, a parallel response was seen for each of the three markers in the
      perfusates of controlled and uncontrolled NHBD kidneys over the 4-h perfusion. A
      highly significant correlation was obtained between GST and Ala-AP activities
      (P<0.0001) and between GST activity and FABP concentration (P<0.0001) in
      corresponding samples. CONCLUSION: In this study, GST, Ala-AP and FABP represent
      equivalent biochemical markers in terms of their ability to quantitate renal
      tissue injury in human NHBD kidneys. However, there may be some advantage in
      using all three analytes to provide complementary information on kidney allograft
      viability.

PMID- 12803839
TI  - A sensitive and practical competitive radioassay for plasma biotin.
AB  - BACKGROUND: Biotin is a water-soluble vitamin which plays an important
      biochemical role in a variety of carboxylase-mediated metabolic reactions.
      Determination of biotin status for the diagnosis of biotin deficiency is crucial.
      METHODS: We describe a solid-phase protein-binding assay involving
      [(125)I]iodostreptavidin as a tracer for the determination of biotin in plasma.
      The assay was conducted in one step by incubation of a fixed amount of
      [(125)I]iodostreptavidin as binding reagent with varying amounts of biotin,
      diluted in biotin-free plasma (standard curve) or unknown samples in tubes
      previously coated with biotin linked to goat antirabbit IgG. Increasing amounts
      of biotin in the standard or unknown samples in tubes previously coated with
      biotin occupy more sites on iodostreptavidin, resulting in fewer counts bound to
      tubes. The effects of the incubation time and temperature on the competitive
      binding of biotin with iodostreptavidin were tested. RESULTS: The detection limit
      of the plasma assay for biotin was 100 pmol/L. Only 100 microL of plasma were
      necessary for the assay, which was performed within 6 h. The dilutions of plasma
      and synthetic biotin gave a parallel response. Plasma biotin levels ranged from
      0.49 to 1.33 nmol/L (mean 0.76 nmol/L) in healthy subjects. The intra and inter
      assay coefficients of variation were 3.5% and 10%, respectively, at a
      concentration of 0.27 nmol/L. CONCLUSIONS: This assay was suitable for the direct
      measurement of biotin in human plasma and was robust and sensitive enough for
      screening for biotin deficiency.

PMID- 12803840
TI  - A novel method for measuring serum ornithine carbamoyltransferase.
AB  - BACKGROUND: Serum ornithine carbamoyltransferase is a diagnostic marker of
      hepatic disorders due to its localization in periportal mitochondria. METHODS: We
      have developed a new method for the determination of serum ornithine
      carbamoyltransferase. It is based on the reverse reaction of ornithine
      carbamoyltransferase, using ornithine-ketoacid aminotransferase, Delta(1)
      pyrroline-5-carboxylate dehydrogenase and glutamate dehydrogenase, which together
      convert citrulline through ornithine to glutamate. The glutamate is then
      quantitatively measured using glutamate oxidase and Trinder's reagent. RESULTS:
      The results obtained by this method agreed well with those obtained using the
      diacetylmonoxime method as a gold standard [correlation coefficient (r) = 0.973
      P<0.001]. The endogenous amino acids sensitive to this method in serum
      (glutamate, ornithine and Delta(1)-pyrroline-5-carboxylate) were eliminated by
      the initial futile reaction. The new method appears to be more accurate at low
      levels of ornithine carbamoyltransferase activity than the diacetylmonoxime
      method. CONCLUSIONS: Here we report a new method for serum ornithine carbamoyl
      transferase assay which might be useful for clinical diagnosis of hepatic
      disorders, including hepatic cancer.

PMID- 12803841
TI  - Definitive angiographic detection of subarachnoid haemorrhage compared with
      laboratory assessment of intracranial bleed in CT-negative patients.
AB  - BACKGROUND: Between 2.5% and 5% of cases of subarachnoid haemorrhage (SAH) give
      negative results for computed tomography (CT) scanning. Recent UK guidelines make
      recommendations as to standardization of laboratory methodology for the detection
      of SAH in individuals with a negative CT scan. We have compared this approach
      with our routine assessment using first-order derivative spectrophotometry, a
      recently reported iterative computer prediction model and measurement of
      cerebrospinal fluid (CSF) ferritin concentration. All methods were judged against
      cerebral angiography as the definitive means of determining patient outcome.
      METHODS: Scanning spectrophotometry of CSF is necessary for both the UK
      guidelines and our in-house method. Absorbance measurements at 360, 405, 414 and
      455 nm are required for the computer model. CSF ferritin concentration was
      measured using a serum method on a DPC Immulite 2000. This gave a value of <12
      microg/L for normal CSF. Ethical approval and informed patient consent to
      additional investigation were obtained. RESULTS: The sensitivity and specificity
      for the UK guidelines method, derivative spectrophotometry (in-house), iterative
      computer model and CSF ferritin were, respectively: 0.8, 1.0; 0.9, 1.0; 0.9, 0.5;
      1.0, 0.78. CONCLUSION: First-order derivative spectrophotometry had best
      concordance with angiography. Combination of this with CSF ferritin measurement
      may improve sensitivity, although the zero-order method recommended in the UK
      guidelines for the detection of an intracranial bleed is more amenable and has
      comparable performance.

PMID- 12803842
TI  - Laboratory results in the elderly: the Sydney Older Persons Study.
AB  - BACKGROUND: The use of laboratory intervals based on younger and healthier
      populations is of questionable validity in older populations. The aim of this
      study was to examine haematological and biochemical profiles in a sample of
      community-dwelling older people and to study the impact of age, disease,
      disability and medications. METHODS: Basic haematological and biochemical values
      were obtained for 338 survivors of a random sample of community-living people
      aged 75 years or over at time of recruitment. These values were compared to the
      laboratory reference intervals and the effects of age, disease, medication and
      disability examined. RESULTS: The distribution of the 35 parameters measured
      differed from those described by the laboratory reference intervals in all but
      four of the variables. The values showed few significant age associations but did
      show associations with disease, disability and drug use. CONCLUSIONS:
      Abnormalities identified in haematological and biochemical testing are not due to
      age but to age-related illnesses. This is contrary to previous studies reporting
      a change in haematological and biochemical parameters purely on the basis of age.
      In the presence of abnormalities, identification and clarification of disease
      states should be made.

PMID- 12803843
TI  - Hypercarotenaemia or hypercarotenoidaemia.
AB  - BACKGROUND: Serum carotenoids consist of a variety of different compounds.
      Xanthoderma may result from an increased concentration of any of the carotenoids.
      METHODS AND RESULTS: High-performance liquid chromatography of serum carotenoids
      shows that a normal chromatogram contains mainly beta-carotene, lutein and
      lycopene. Serum alpha- and beta-carotene, beta-cryptoxanthin, lycopene, lutein
      and zeaxanthin were found to be increased in the investigation of
      hypercarotenaemia. CONCLUSION: Patients presenting with possible xanthoderma
      should have a dietary history taken and serum sent for carotenoid analysis.

PMID- 12803844
TI  - Retrospective analysis of abnormal 24-h urinary free catecholamine concentration
      in screening for phaeochromocytoma.
AB  - BACKGROUND: Patients with hypertension often have increased 24-h excretion of
      urinary free catecholamines (UFCA) compared with normotensive patients, but the
      extent to which beta-blockade and other antihypertensive agents affect 24-h UFCA
      concentrations remains unclear. Consequently, many patients with slightly
      elevated 24-h UFCA concentrations are not adequately investigated for the
      presence of phaeochromocytoma. METHOD: We undertook a retrospective study on
      patients with at least one abnormal 24-h urinary collection of adrenaline (Adr),
      noradrenaline (NA) or dopamine (DA) between July 1997 and December 1999 to assess
      these issues. RESULTS: Of the 168 patients identified with raised 24-h UFCA
      concentrations, 106 with hospital notes were audited. Of the 46 patients whose
      values were more than twice the upper reference limit, 24 had their result
      confirmed with a repeat sample and only 10 underwent computed tomography or m
      iodobenzylguanidine scanning. Two patients of these 10 had a phaeochromocytoma.
      We observed that hypertension correlated with significantly increased NA
      excretion compared with normotensive patients (median value 490+/-222 nmol per 24
      h versus 304+/-229 nmol per 24 h, P<0.005). Patients on beta-blockers showed a
      trend towards significantly increased NA excretion (P=0.08). CONCLUSIONS: Many
      patients with abnormal 24-h UFCA excretion are not thoroughly investigated for
      the presence of phaeochromocytoma. NA concentration is significantly raised above
      the reference limit for patients with hypertension, and the use of beta-blockers
      showed a trend towards a further elevation in NA concentrations. Care must
      therefore be taken when interpreting abnormal NA concentrations in patients with
      hypertension or in those taking beta-blockers.

PMID- 12803845
TI  - Comparison of lipid and non-lipid markers of atherosclerosis in arterial versus
      venous blood.
AB  - BACKGROUND: Early studies have suggested that there may be differences in the
      concentration of lipoprotein particles and their associated apolipoproteins in
      arterial and venous blood and that this gradient might explain a proclivity to
      develop atherosclerotic lesions. The aim of this study was to use current methods
      of analysis to determine levels of these components, including particle densities
      and several common inflammatory markers in arterial and venous blood. METHODS:
      Samples of arterial and venous blood were obtained nearly simultaneously in 26
      patients undergoing right and left heart catheterization. Analyses were performed
      using enzymatic, immunoturbidimetric and ultracentrifugation assays. RESULTS:
      Data obtained for total cholesterol, triglyceride, HDL-cholesterol, LDL
      cholesterol, HDL and LDL particle density, high sensitivity C-reactive protein,
      serum amyloid-A and apoprotein B-100 concentrations in arterial and venous blood
      did not demonstrate any significant difference in the means. CONCLUSION: Arterial
      and venous blood can be used interchangeably to study the effect of blood
      concentrations of common soluble surrogate markers of atherosclerosis.

PMID- 12803846
TI  - Clinical biochemical tissue monitoring during ischaemia and reperfusion in major
      vascular surgery.
AB  - BACKGROUND: Major vascular surgery with aortic cross-clamping is associated with
      temporary ischaemia of the lower limb due to lack of tissue blood flow. The
      present study was designed to determine if the short-term changes in cellular
      metabolism occurring during this situation can be detected by subcutaneous
      microdialysis. It was also hoped to ascertain if this new technique is useful in
      the continuous bedside monitoring of metabolism during aortic surgery. METHODS:
      In a controlled clinical study 20 patients undergoing elective aortic surgery
      were monitored using microdialysis probes that were inserted in the subcutaneous
      tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial
      fluid was obtained and the concentrations of glucose and lactate during lower
      limb ischaemia and during reperfusion were measured and compared with
      concentrations observed in fluid obtained from the non-ischaemic control tissue.
      RESULTS: Circulatory occlusion caused an immediate and significant decrease in
      the glucose/lactate ratio from 3.1+/-1.3 to 0.48+/-0.5 (P<0.05) that returned to
      preocclusion values within 2 h of commencing reperfusion. CONCLUSION: We suggest
      that microdialysis may be used both to assess acute changes in tissue metabolism
      during ischaemic periods and also to act as an additional tool for the detection
      of peri-operative acute variations in limb blood flow.

PMID- 12803847
TI  - Vitamin A deficiency presenting as night blindness during pregnancy.
AB  - We describe a patient with a 6-year history of pancreatic malabsorption following
      surgical subtotal pancreatectomy. She presented at 33 weeks of pregnancy with
      night blindness as a result of vitamin A deficiency. She had had two successful
      pregnancies 9 and 8 years previously, giving birth to a healthy baby boy on each
      occasion. We suggest that patients with long-term malabsorption due to intestinal
      or pancreatic disease should have vitamin A status checked prior to and during
      pregnancy so that prompt supplementation can be commenced if necessary. The
      possibility that vitamin A deficiency may be contributing to anaemia present in
      pregnancy should also be considered.

PMID- 12803848
TI  - Severe hypercalcaemia secondary to isolated adrenocorticotrophic hormone
      deficiency and subacute thyroiditis.
AB  - Severe hypercalcaemia is usually due to either neoplastic disease or primary
      hyperparathyroidism. Rarer causes do exist, and exceptionally these may occur
      concomitantly. We describe the case of a 45-year-old man who presented in a
      debilitated state with severe hypercalcaemia (total serum calcium 3.56 mmol/L,
      albumin 35 g/L) and suppressed serum parathyroid hormone concentration. It was
      initially suspected that he had neoplastic disease, but routine thyroid function
      tests demonstrated evidence of thyrotoxicosis [thyroid-stimulating hormone <0.05
      mU/L (0.15-3.5); free thyroxine 75 pmol/L (8-27); total tri-iodothyronine 7.0
      nmol/L (1.0-2.6)], which was probably secondary to a silent or subacute
      thyroiditis. After extensive investigation, it was established that the patient
      also had isolated adrenocorticotrophic hormone deficiency, presumably secondary
      to lymphocytic hypophysitis. Glucocorticoid therapy resulted in a dramatic
      improvement in the patient's clinical state and 1 year later he remained
      euthyroid and normocalcaemic.

PMID- 12803849
TI  - Prolactin and macroprolactin: a case report of hyperprolactinaemia highlighting
      the interpretation of discrepant results.
AB  - Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass
      complexes of prolactin) to various degrees. Therefore it is generally assumed
      that the widely differing results by methods that measure both moieties to a
      differing extent are due to the presence of macroprolactin. We present a case
      which challenges such an assumption and suggest that precipitation by
      polyethylene glycol is the most reliable screen for identifying macroprolactin
      (and/or interfering antibodies if present).

PMID- 12803853
TI  - Monitoring the chloroquine sensitivity of Plasmodium vivax from Calcutta and
      Orissa, India.
AB  - Chloroquine-resistant Plasmodium vivax malaria was first reported in India in
      1995. This report led to the round-the-year monitoring, in Calcutta (West Bengal)
      and Mayurbhanj district (northern Orissa), of the in-vivo sensitivity of local P.
      vivax to chloroquine (CQ). Between January 1998 and December 2001, 800 cases with
      microscopically confirmed P. vivax malaria were enrolled in the study. Each was
      given CQ in the regimen recommended both by the Government of India and the World
      Health Organization (i.e. a total of 25 mg/kg, over 3 days). Only six cases, of
      the 480 who completed the scheduled 28 days of follow-up, failed to clear their
      parasitaemias by day 5. Even these six cases had only low-level parasitaemias on
      day 5, and all were aparasitaemic by day 7. In the study area, despite the wide
      spread abuse of CQ and the increasingly frequent reports of CQ-resistant P.
      falciparum, CQ appears to remain an effective drug in the treatment of P. vivax.

PMID- 12803854
TI  - The chemotherapy of rodent malaria. LXI. Drug combinations to impede the
      selection of drug resistance, part 4: the potential role of 8-aminoquinolines.
AB  - The influence of combinations containing the blood schizontocides chloroquine
      (CQ) or mefloquine (MEF), together with the 8-aminoquinolines (8AQ) primaquine
      (PQ) or the new, long-acting compound, tafenoquine (TAF), on the rate of
      selection of resistance to the individual compounds was examined using the
      asexual, intra-erythrocytic stages in rodent malaria models. The two main
      procedures used were a 'serial technique' (ST) and the '2%- relapse technique'
      (2%RT). The ST provided evidence for the contention that a combination with PQ
      slowed the selection of resistance to CQ or MEF; it has been shown previously
      that synergism exists between CQ and either PQ or TAF in rodent malaria. Data
      obtained with the 2%RT, and three parasite lines derived from Plasmodium berghei
      N (the 238B line), P. chabaudi ASS (the 238C line) or P. yoelii ssp. NS (the 238Y
      line), indicated that resistance to TAF used alone is acquired rapidly under drug
      pressure and that this resistance is stable when selection pressure is removed.
      In the 2%RT, resistance to CQ developed when another line of P. chabaudi (AS15)
      was exposed to that compound alone, although more slowly than the development of
      resistance to TAF in the 238C line. However, treatment of a TC line of P.
      chabaudi, developed in a 2%RT using a combination of CQ with TAF, led to little
      resistance to either compound. A totally unforeseen phenomenon was the appearance
      of a high level of resistance to CQ in the 238C line of P. chabaudi that had been
      exposed only to TAF; this was not observed with the 238B or 238Y lines. Attention
      has been refocused recently on the use of 8AQ for prophylaxis in man. It remains
      to be determined if resistance in the asexual intra-erythrocytic forms is carried
      over to the other stages of the malarial life-cycle, especially the hepatic, pre
      erythrocytic schizonts. The implications of the present results for the possible
      clinical deployment of 8AQ in the future are discussed. It is concluded that,
      whereas use of an 8AQ alone carries a high risk of selecting resistance,
      combinations containing 8AQ may have a place in the protection of blood
      schizontocides that are to be deployed in endemic areas. Furthermore, the
      inherent gametocytocidal action of the 8AQ should promote the reduction of
      transmission.

PMID- 12803855
TI  - In-vitro uptake of vitamin A by Plasmodium falciparum.
AB  - The vitamin-A uptake of Plasmodium falciparum was investigated by culturing a
      standard isolate of the parasite (FCR-3) with (3)H-labelled vitamin A, at
      concentrations of the vitamin corresponding to those normally present in human
      serum. The (3)H-labelled vitamin A accumulated in the parasites from each culture
      in a parasitaemia-dependent manner. The radioactivity detected in the parasites
      increased with parasite maturation from the ring to the late-trophozoite stage.
      In addition, most of the radioactivity incorporated into the parasite cells was
      in the cytoplasm. The accumulation of vitamin A in the cytoplasm of late
      trophozoites indicates that P. falciparum may use vitamin A, from its human host,
      as an antioxidant, to protect itself from oxidative stress while intra
      erythrocytic. The amount of the vitamin taken up by the parasite in vitro is
      small compared with the deficit that sometimes causes severe hypovitaminosis A in
      malaria cases. Consumption of vitamin A by the parasites together with the
      systemic decreases in non-enzymatic antioxidants that are seen in malaria may
      together cause this characteristic hypovitaminosis.

PMID- 12803856
TI  - Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not
      only in the monocytes of visceral leishmaniasis cases but also in cultured THP1
      cells.
AB  - Apparently for the first time, the peripheral blood monocytes of individuals with
      active visceral leishmaniasis (VL) have been found to show reduced expression of
      interferon gamma receptor-1 (IFNGR1). Since interferon gamma is the main cytokine
      responsible for defence against leishmanial parasites, it was thought possible
      that effective antileishmanial drugs may up-regulate IFNGR1. Confocal microscopy
      confirmed that monocytes from VL patients who had been treated, with sodium
      antimony gluconate (SAG), did display IFNGR1 up-regulation. To see if this effect
      could be mimicked in vitro, IFNGR1 expression was investigated using a human
      macrophage cell line (THP1), northern blotting and confocal microscopy. When the
      THP1 cells were treated with SAG or pentamidine, their expression of the receptor
      was increased. This drug-induced up-regulation was more intense if the
      macrophages were infected with Leishmania donovani than if they were left
      uninfected. The possibility that at least some antileishmanial drugs act by up
      regulating IFNGR1 expression needs to be explored further. A good model for
      investigating the mechanisms of action of antileishmanial drugs might be based on
      the THP1 cell line.

PMID- 12803857
TI  - Therapeutic evaluation of free and nanocapsule-encapsulated atovaquone in the
      treatment of murine visceral leishmaniasis.
AB  - The activities of free atovaquone (ATV) and of poly(D,L-lactide) nanocapsules
      loaded with the drug, in the treatment of mice with visceral leishmaniasis caused
      by Leishmania infantum, were compared. Each mouse was infected intravenously with
      2x10(7) promastigotes, on day 0. On days 15, 17 and 19, most of the infected mice
      were treated either with free ATV, in a dimethylsulphoxide/cremophor/water
      mixture, or with the ATV-loaded nanocapsules (at, respectively, 0.2-1.6 and 0.125
      1.0 mg ATV/kg, on each treatment day). The rest of the mice were left untreated,
      as controls. All the mice were killed on day 21 and dissected so that their
      livers and spleens could be weighed. The liver parasite burdens, evaluated using
      the Stauber method, indicated that the ATV-loaded nanocapsules were significantly
      more effective than the free drug. In nanocapsules, for example, a total dose of
      3.0 mg ATV/kg reduced liver burdens by 71.3%, whereas treatment with a higher
      total dose of the free drug (4.8 mg/kg) only cut the number of liver parasites by
      34.4%. The dose-response data indicated that livers would have been cleared of
      parasites if the nanocapsule preparation had been given as three doses each
      equivalent to 3 mg ATV/kg, whereas the maximum suppression possible with the free
      drug would have been about 61%, whatever the dose.

PMID- 12803858
TI  - Hantavirus infection in people inhabiting a highly endemic region of the Gran
      Chaco territory, Paraguay: association with Trypanosoma cruzi infection,
      epidemiological features and haematological characteristics.
AB  - The seroprevalences of anti-hantavirus antibodies were determined in 712
      individuals (551 Indians, 140 Mennonites of German ancestry, and 21 Paraguayans
      of Spanish ancestry) inhabiting a region of western Paraguay in the Gran Chaco
      territory of South America. The overall seroprevalence of hantavirus infection
      among the 712 subjects, who were aged 2-80 years, was 42.7% (45.2% in the Indians
      and 34.2% in the non-Indians). Of the 672 subjects also checked for antibodies
      against Trypanosoma cruzi, 226 (33.6%) were seropositive for this protozoan
      parasite. The results of a multivariate regression analysis indicated that, after
      adjusting for age, sex, setting of residence (rural/urban) and infection with the
      human T-cell leukaemia/lymphoma virus type II (HTLV-II), a T. cruzi-seropositive
      individual was 1.73 times more likely to be hantavirus seropositive than a T.
      cruzi-seronegative individual. Living in a rural setting increased the risk of
      being hantavirus seropositive 2.17-fold. In both the Indians and non-Indian
      subpopulations, hantavirus seroprevalence increased with age in both sexes, but
      only in the non-Indian supopulation was this increase significantly greater in
      males than in females. Hantavirus seropositivity was significantly associated
      with thrombocytosis, even after adjusting for the relevant confounders.

PMID- 12803859
TI  - Inhibition of the transcription of the Escherichia coli O157:H7 genes coding for
      shiga-like toxins and intimin, and its potential use in the treatment of human
      infection with the bacterium.
AB  - Reverse-transcription PCR (RT-PCR) was used to assess the effects, in vitro, of
      rifampicin on the transcription of the eaeA, stx1 and stx2 genes (coding for
      intimin and shiga-like toxins I and II, respectively) of seven strains of
      Escherichia coli O157:H7 associated with human infection. Each strain was found
      to possess all three genes and, in the absence of rifampicin, all seven strains
      transcribed eaeA and stx2 (three strains did not transcribe their stx1 genes).
      Transcription of all three genes was inhibited (as witnessed by a negative result
      in the RT-PCR), however, when the strains were incubated, at 37 degrees C, with
      rifampicin at 4 microg/ml (found to be the minimum concentration of this
      antimicrobial agent that inhibited the multiplication of E. coli O157:H7). The
      results of an assay based on reversed passive latex agglutination (RPLA) revealed
      that exposure of the bacteria to 4 microg rifampicin/ml led to a 12-fold decrease
      in the release of shiga-like toxin I and a 16-fold decrease in the release of
      shiga-like toxin II. As rifampicin is capable of inhibiting the in-vitro
      transcription of the genes encoding the shiga-like toxins and intimin attachment
      protein of E. coli O157:H7, it may be useful in the treatment of human infections
      with strains of this bacterium. Studies are now underway to assess the in-vitro
      and in-vivo effects of rifampicin, at both transcription-inhibitory and
      bactericidal concentrations, on E. coli O157:H7. The effects of other agents on
      the inhibition of the expression or activity of the shiga-like toxins and intimin
      attachment protein will also be determined.

PMID- 12803860
TI  - The impact of vector control on Triatoma dimidiata in the Guatemalan department
      of Jutiapa.
AB  - In 2000, a national control operation against the triatomine vectors of
      Trypanosoma cruzi, based on house spraying with residual pyrethroid insecticides,
      was initiated in Guatemala. The impact of the operation against Triatoma
      dimidiata in the most heavily infested department, Jutiapa, was evaluated by pre-
      and post-spraying surveys of the vector populations. Of the houses checked for
      Tri. dimidiata in the baseline surveys, 18.3% were found to be infested with the
      bug, and in 12.1% of the villages investigated more than half of the houses were
      found to be infested. The later survey was conducted after 24,250 houses and
      their associated peridomestic structures (in the 336 villages in which >5% of the
      houses had been found infested in the pre-spraying survey) had been sprayed. As a
      result of just this one round of spraying, the mean percentage of houses found
      infested in each of the villages surveyed twice fell from 36.0% to 8.9%. After
      the spraying, the percentage of houses infested in each sprayed village was never
      >50%, and the houses in 35.2% of the sprayed villages that were re-surveyed
      appeared to have been completely cleared of triatomine bugs. Re-infestation and
      colonization were mainly observed inside the houses, probably indicating that
      some indoor bugs survived the spraying round. If the department of Jutiapa is to
      be freed and kept free from domestic infestation, the efficacy of the insecticide
      spraying needs to be improved, spraying techniques need to be reviewed, and
      insecticides need to be re-applied at regular intervals. An effective vector
      surveillance system (preferably one in which community participation is
      encouraged) is also essential.

PMID- 12803861
TI  - Measuring the job performance of district health managers in Latin America.
AB  - In resource-poor countries, district health managers (DHM) have gained importance
      as health systems have become decentralized. Although the roles and key functions
      of DHM have been described in the literature, there appears to have been no
      analysis of what they are really doing. In this context, the knowledge and job
      performance of 218 DHM from nine Latin American countries were investigated. The
      study was based on 12 performance indicators, two self-administered
      questionnaires (which included internal consistency tests), formal and informal,
      check interviews in the work place, and direct observations of the DHM. The DHM
      investigated were found to be particularly weak in systems management (community
      involvement and intersectoral co-operation), monitoring activities and the
      systematic organization of meetings. They were rarely involved in the
      identification of priority health problems or of high-risk groups, and failed to
      use health-service indicators sufficiently for the analysis of the district
      health system. The managers were stronger in relation to the organization of
      technical meetings and the development and implementation of local health plans.
      Factors associated with good management performance were a favourable
      organizational structure (including written job descriptions and support from the
      authorities), 'decision power' (i.e. the ability to select and appoint new staff
      ) and a good knowledge of the local situation. In Latin America, at least, DHM
      need to be better prepared, supervised and supported.

PMID- 12803862
TI  - Retinal changes in adults with cerebral malaria.

PMID- 12803863
TI  - Babesia microti infection of anthropophilic ticks (Ixodes ricinus) in Hungary.

PMID- 12803864
TI  - Footcare among lymphoedema patients attending a filariasis clinic in South India:
      a study of knowledge and practice.

PMID- 12803865
TI  - A randomized comparison of chloroquine and chloroquine plus ketotifen in the
      treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.
AB  - The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has
      created urgent needs for the evaluation of alternative antimalarial drugs that
      are effective, safe, readily available and affordable. Ketotifen, a histamine
      H(1)-receptor antagonist that reverses CQ resistance in P. falciparum in vitro,
      may potentially enhance the effects of CQ in vivo. The effects of oral treatment
      with CQ alone (30 mg/kg base given over 3 days) were compared with those of this
      CQ regimen combined with ketotifen fumarate (0.25 mg at presentation followed by
      0.125 mg/kg every 8 h for 5 days). The subjects were 145 children aged 1-10 years
      who were suffering from acute, symptomatic, uncomplicated, P. falciparum malaria:
      74 given CQ alone and 71 given CQ plus ketotifen (CQK). Although the mean fever
      clearance time was significantly shorter following treatment with CQK than after
      treatment with CQ alone, all other therapeutic responses were similar in the two
      treatment groups. Among siblings in whom there was clustering of infections, the
      likelihood of cure was also similar in the two treatment groups. Retreatment of
      17 CQ-treatment failures with CQK produced a cure in six children, and
      retreatment of 22 CQK-treatment failures with CQK produced a cure in eight
      children. Retreatment of all drug failures with a combination of amodiaquine plus
      pyrimethamine-sulfadoxine resulted in complete clearance of parasitaemia and
      symptoms within 2-3 days and a cure 'rate' of 100% on day 28. The prevalences and
      intensities of gametocytaemias on day 3 or days 3, 7 and/or 14 combined were
      similar in the two groups. Adverse drug reactions were always tolerable, and
      limited to pruritus, gastro-intestinal disturbances, drowsiness and weight gain;
      the latter two adverse effects were significantly more frequent in those treated
      with CQK than in those given CQ alone. Haematological and biochemical parameters
      were not adversely affected by either treatment regimen. The findings indicate
      that - at least at the dosing regimen used in the present study and among
      children with acute, uncomplicated, P. falciparum malaria from Ibadan - the
      addition of ketotifen to CQ produced little or no significant enhancement of the
      antimalarial effect of CQ.

PMID- 12803866
TI  - Molecular survey of Plasmodium falciparum resistance in south-eastern Iran.
AB  - In south-eastern Iran, the sulfadoxine-pyrimethamine (SP) combination has been
      used to treat malaria caused by chloroquine-resistant Plasmodium falciparum. To
      explore the molecular basis of antimalarial resistance in this region, the dhfr,
      dhps and pfcrt genes of 50 clinical isolates of P. falciparum, collected from
      cases of uncomplicated malaria in 2000-2001, were checked for the point mutations
      that appear associated with SP or chloroquine (CQ) resistance. The results of the
      study, which was based on a PCR followed by DNA sequencing, indicated that all 50
      isolates presented the DHFR S108N mutation associated with pyrimethamine
      resistance. Seven isolates (14%) had a triple DHFR mutation (S108N, N51I, C59R)
      and 32 (64%) had a double mutation in this domain. Thirty-nine isolates (78%) had
      the wild-type DHFR 51 codon but only 15 (30%) had the wild-type DHFR 59 codon.
      Eleven isolates (22%) only had the DHFR S108N mutation. All isolates had the wild
      type DHPS 436 and 540 codons and all but two of the isolates had the wild-type
      DHPS 437 codon. All isolates but one had the PFCRT K76T mutation associated with
      CQ treatment failure. The results of this preliminary investigation indicate that
      SP may remain the treatment of choice for cases of uncomplicated malaria in south
      eastern Iran.

PMID- 12803867
TI  - Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive
      malarious splenomegaly and acute haemolysis.
AB  - A cluster of 16 cases of hyper-reactive malarious splenomegaly (HMS) with severe,
      acute haemolysis, from an isolated, Venezuelan, Yanomami population, was
      prospectively investigated. Nine (69%) of the 13 HMS sera investigated but only
      one (7%) of 14 control sera (P < 0.005) contained elevated titres (of at least
      1:32) of complement-fixing IgM cold agglutinins (CA). The CA detected had
      specificity for both the I and i blood-group antigens (with a relative
      predominance of anti-I) and wide thermal stability. The mean reciprocal CA titre
      was much higher for the HMS sera than for the control samples (59.16 v. 2.28; P <
      0.001). Indirect tests for antiglobulin were positive for two of the 13 HMS cases
      (but none of 14 controls) investigated; all of the direct tests for antiglobulin
      gave negative results. The seven HMS cases checked, using an assay based on a
      nested PCR which amplified species-specific ribosomal sequences from Plasmodium
      vivax or P. falciparum, each yielded the PCR product that indicated P. vivax
      infection. However, only six (25%) of the 24 control samples (collected, at the
      same time as the HMS samples, from asymptomatic adults from the same Yanomami
      population) were PCR-positive (P < 0.001). In some cases at least, the acute
      severe episodes of haemolysis occasionally seen in HMS appear to be associated
      with an auto-immune, cold-agglutinin-mediated response triggered by non-patent
      parasitaemias.

PMID- 12803868
TI  - Use of a rapid, single-round, multiplex PCR to detect malarial parasites and
      identify the species present.
AB  - A new, rapid assay, based on a single-round, multiplex PCR, can be used to detect
      Plasmodium falciparum, P. vivax, P. malariae or P. ovale in human blood. The PCR,
      which targets the conserved 18S small-subunit RNA genes of the parasites, not
      only permits a malarial infection to be detected but also allows each Plasmodium
      species present to be identified, even in cases of mixed infection.

PMID- 12803869
TI  - Types of arrhythmia among cases of American trypanosomiasis, compared with those
      in other cardiology patients.
AB  - The frequencies of each type of arrythmia were investigated, by age and sex,
      among 3056 Brazilian patients with cardiac arrhythmia. Each patient investigated
      had been tested serologically for American trypanosomiasis and 1013 had been
      found seropositive for the disease. In general, the seropositive 'chagasic'
      patients were each likely to be suffering from more types of arrhythmia than the
      seronegative 'non-chagasic', with means of 1.81 and 1.03 types/patient,
      respectively. Right-branch bundle blocks (RBBB), ventricular extrasystoles (VE)
      and left anterior hemiblocks (LAHB) were the commonest cardiac arrhythmias among
      the chagasic patients, and each of these types of arrhythmia (alone or with other
      types of arrythmia) was more frequent in the chagasic patients than the non
      chagasic. The incidence of RBBB among the arrhythmic varied significantly with
      age in the non-chagasic patients (increasing with age among both the males and
      females) but not among the chagasic subjects. When the frequencies of each type
      of arrythmia and each combination of types were compared, the co-occurrence of
      RBBB and another type of arrhythmia was almost indicative of American
      trypanosomiasis (occurring in 30.6% of the chagasic subjects but only 2.6% of the
      non-chagasic). Similarly, only 0.4% of the non-chagasic patients but 7.4% of the
      chagasic had RBBB, VE and LAHB concurrently. However, the frequencies of RBBB in
      isolation (i.e. with no other, concurrent, electrocardiographic abnormality), VE
      in isolation, or LAHB in isolation were not significantly different in the
      chagasic and non-chagasic patients.

PMID- 12803870
TI  - Domestic animals as reservoirs for sleeping sickness in three endemic foci in
      south-eastern Uganda.
AB  - The persistence of sleeping sickness (human African trypanosomiasis) in some
      areas of south-eastern Uganda has necessitated further investigations, focusing
      mainly on domestic animals as reservoirs of this disease in three agro-ecological
      zones. The inter-zone differences in the prevalences of trypanosome infection
      among cattle (P < 0.001) and pigs (P < 0.001) were significant. Overall, 5.0% of
      the cattle, 13.9% of the pigs and 0.4% of the small ruminants investigated were
      found to be infected with parasites of the Trypanosoma brucei subgroup. The
      results of blood incubation infectivity tests (BIIT) indicated that all of the T.
      brucei-subgroup isolates from cattle in Kamuli district (zone I) were human-serum
      sensitive. Of the zone-I pigs found infected, however, almost all (82.5%) were
      considered to be infected with T. brucei and many (30.2%) carried human-serum
      resistant T. brucei. Pig-tsetse-human appears to be a major transmission cycle in
      zone I. In Mukono district (zone II), 10.5% and 26.1% of the T. brucei isolates
      from cattle and pigs, respectively, were human-serum-resistant, indicating that
      cattle-tsetse-human and pig-tsetse-human are major transmission cycles in zone
      II. In Tororo district (zone III), 47.3% of the T. brucei isolates from cattle
      were human-serum-resistant but there were no T. brucei isolates from pigs,
      indicating that cattle-tsetse-human is the major transmission cycle.
      Interestingly, as the only T. brucei isolate from sheep in zone III was human
      serum-resistant, there may also be a sheep-tsetse-human cycle. In south-eastern
      Uganda, control efforts must be designed to eliminate the parasites not only from
      cattle but also from pigs and small ruminants.

PMID- 12803871
TI  - Failure of an ointment based on IR3535 (ethyl butylacetylaminopropionate) to
      prevent an outbreak of cercarial dermatitis during swimming races across Lake
      Annecy, France.
AB  - Cercarial dermatitis, a re-emerging disease world-wide, may affect those engaged
      in water sports. Many of those who swim in the annual cross-lake races at Annecy
      in France, for example, develop such dermatitis. In an attempt to see whether
      ethyl butylacetylaminopropionate (IR3535) would protect swimmers from the
      dermatitis, the exposed skin on the right side of each of 78 participants in the
      cross-lake races of 2001 was treated with IR3535-based ointment. When contacted
      by telephone during the week following the races, 64 (82%) of the subjects
      reported that they had developed cercarial dermatitis. Subjects with a past
      history of cercarial dermatitis were more likely to report an attack in 2001 than
      those who said that they had never had such dermatitis prior to 2001 (P=0.001).
      The skin lesions were scattered all over the body in 89% of the cases and limited
      to the left side of the body in 11%. Of the 63 cases who reported time of onset,
      32 (51%) had noticed lesions within an hour of the race. The mean duration of
      clinical manifestations was 4.8 days (range=30 min-18 days). The clinical
      manifestations were significantly more severe in the subjects aged >16 years than
      in the younger subjects, although these two age-groups swam in separate races.
      Thirty-one of the affected subjects attempted to cure their dermatitis, using any
      of five different treatments. Overall, the results were disappointing, with the
      IR3535-based ointment, which had initially been developed as an insect repellent,
      appearing to offer little, if any, protection against cercarial dermatitis.

PMID- 12803872
TI  - The co-administration of ivermectin and albendazole--safety, pharmacokinetics and
      efficacy against Onchocerca volvulus.
AB  - A randomized, double-blind, placebo-controlled trial was conducted, to determine
      whether the co-administration of ivermectin with albendazole is safe and more
      effective against Onchocerca volvulus than ivermectin alone, and whether a
      significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis
      patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or
      the combination. Safety was determined from the results of detailed clinical and
      laboratory examinations before treatment, during hospitalization and on day 30.
      Microfilaricidal efficacy was estimated from the reductions in skin counts
      between day 0 (pretreatment) and day 30. To determine efficacy against the adult
      worms, two independent observers examined histology slides prepared from nodules
      excised on day 180; changes in the skin counts of skin microfilariae between days
      30 and 365 provided additional indicators of the level of adulticidal activity.
      Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined
      over 72 h post-treatment. The co-administration of ivermectin with albendazole
      did not produce more severe adverse effects than ivermectin alone. Both nodule
      examiners found that the combination was not macrofilaricidal and that it was not
      clearly superior to ivermectin alone in the effects on reproductive activity;
      this was supported by the similar efficacy of the two regimens in the suppression
      of skin microfilariae. There was no significant pharmacokinetic interaction.
      Although the co-administration of ivermectin with albendazole appears safe, it
      offers no advantage over ivermectin alone in the control of onchocerciasis. The
      combination does not require an alteration in the dosage of either component.

PMID- 12803873
TI  - Human infection with Wuchereria bancrofti in Matara, Sri Lanka: the use, in
      parallel, of an ELISA to detect filaria-specific IgG4 in urine and of ICT card
      tests to detect filarial antigen in whole blood.
AB  - The ICT card test to detect circulating filarial antigen and an ELISA that
      detects filaria-specific urinary IgG(4) were each used to screen 473 subjects
      from a community in Sri Lanka where Wuchereria bancrofti is endemic. When the ICT
      test was used as the gold standard, the ELISA was found to have a sensitivity of
      91.2%. However, far more of the subjects were found ELISA-positive than ICT
      positive (76.5% v. 31.1%). The youngest children studied (aged 1-10 years) were
      similar to the adult subjects in terms of the prevalence of antigenaemia (33.8%)
      and the prevalence (72.1%) and concentration of filaria-specific IgG(4) in their
      urine. Therefore, especially as urine samples are easier, less painful and safer
      to collect than blood samples, the ELISA may be particularly useful to screen
      very young and school-age children, to estimate current levels of transmission in
      a particular area.

PMID- 12803874
TI  - Infection with hepatitis B and C viruses and human retroviruses (HTLV-I and HIV)
      among high-risk Lebanese patients.
AB  - Three groups of Lebanese patients (haemophiliacs, patients on cycled cancer
      chemotherapy who were regularly receiving blood transfusions, and intravenous
      drug users) and a control group of healthy blood donors were checked for markers
      of infection with hepatitis viruses (B and C) and human retroviruses (HIV and
      HTLV-I). Compared with the controls, all three groups of patients were more
      likely to be seropositive for antibody to hepatitis C virus (anti-HCV), and the
      haemophiliacs and cancer patients (but not the relatively young drug users) were
      more likely to be seropositive for hepatitis B virus (HBV). All the haemophiliacs
      and cancer patients found to be carrying the surface antigen of HBV (HBsAg)
      and/or to be seropositive for anti-HCV had given the same result when tested
      before the screening of blood and blood products for HBsAg and anti-HCV became
      routine practice in Lebanon (a decade before the present study). The four
      intravenous drug users (IVDU) found seropositive for HBV (two cases) or anti-HCV
      (two cases) had seroconverted in the 2 years prior to the present study. In
      addition to highlighting the problem of HCV infection among IVDU, the present
      results emphasise the need for the careful screening of donated blood for all
      blood-borne viruses, and for the exclusive use of disposable equipment in the
      management of cancer patients. The anti-HBV vaccination of IVDU is recommended
      but only the results of further clinical evaluation will show whether the similar
      vaccination of patients on cycled cancer chemotherapy is of value. Although none
      of the patients or controls was found positive for anti-HIV-1, anti-HIV-2 or anti
      HTLV-I, the routine screening of blood and blood products for these viruses
      (particularly for HIV) should remain mandatory.

PMID- 12803875
TI  - Sandflies (Diptera: Psychodidae) in the Bar area of Montenegro (Yugoslavia).
AB  - The species and ecology of sandflies present in the coastal district of Bar,
      which lies in Montenegro, an endemic focus of visceral leishmaniasis (VL), were
      investigated in 1996-1999. A mean of 10 cases of VL and a greater number of viral
      infections (some of which are attributed to pathogens transmitted by sandflies)
      are diagnosed each year in this district. Phlebotomus papatasi, P. perfiliewi, P.
      tobbi, P. neglectus and Sergentomyia minuta were collected, P. perfiliewi being
      recorded for the first time in Montenegro. The ecology and distribution of each
      of these five species are described and their role, if any, in the transmission
      of Leishmania to humans is discussed.

PMID- 12803876
TI  - Trichuris trichiura infection is associated with the multiplicity of Plasmodium
      falciparum infections, in Thailand.

PMID- 12803877
TI  - Aggregated oviposition in Simulium ochraceum s.l. (Diptera: Simuliidae), an
      important neotropical vector of Onchocerca volvulus.

PMID- 12803878
TI  - The spread of Biomphalaria pfeifferi in the Niger River valley, Niger.

PMID- 12803879
TI  - Towards antibacterial strategies: studies on the mechanisms of interaction
      between antibacterial peptides and model membranes.
AB  - Lipopolysaccharides (LPSs) play a dual role as inflammation-inducing and as
      membrane-forming molecules. The former role attracts significantly more attention
      from scientists, possibly because it is more closely related to sepsis and septic
      shock. This review aims to focus the reader's attention to the other role, the
      function of LPS as the major constituent of the outer layer of the outer membrane
      of Gram-negative bacteria, in particular those of enterobacterial strains. In
      this function, LPS is a necessary component of the cell envelope and guarantees
      survival of the bacterial organism. At the same time, it represents the first
      target for attacking molecules which may either be synthesized by the host's
      innate or adaptive immune system or administered to the human body. The
      interaction of these molecules with the outer membrane may not only directly
      cause the death of the bacterial organism, but may also lead to the release of
      LPS into the circulation. Here, we review membrane model systems and their
      application for the study of molecular mechanisms of interaction of peptides such
      as those of the human complement system, the bactericidal/permeability-increasing
      protein (BPI), cationic antibacterial peptide 18 kDa (CAP18) as an example of
      cathelicidins, defensins, and polymyxin B (PMB). Emphasis is on electrical
      measurements with a reconstitution system of the lipid matrix of the outer
      membrane which was established in the authors' laboratory as a planar asymmetric
      bilayer with one leaflet being composed solely of LPS and the other of the
      natural phospholipid mixture. The main conclusion, which can be drawn from these
      investigations, is that LPS and in general its negative charges are the dominant
      determinants for specific peptide-membrane interactions. However, the detailed
      mechanisms of interaction, which finally lead to bacterial killing, may involve
      further steps and differ for different antibacterial peptides.

PMID- 12803880
TI  - C2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage
      cells through down-regulating the activation of Akt.
AB  - The effect of C(2)-ceramide, a membrane-permeable ceramide analogue, on nitric
      oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was
      studied. The non-toxic concentration of C(2)-ceramide inhibited LPS-induced NO
      production. It was due to the attenuated expression of the inducible type of NO
      synthase (iNOS). C(2)-ceramide did not influence the phosphorylation of a series
      of mitogen-activated protein (MAP) kinases in response to LPS. On the other hand,
      C(2)-ceramide down-regulated the phosphorylation of Akt in LPS-stimulated RAW
      264.7 cells, followed by the impairment of nuclear factor (NF)-kappaB activation.
      Moreover, the Akt dominant-negative mutant inhibited LPS-induced NO production.
      C(2)-ceramide was suggested to inhibit LPS-induced NO production through down
      regulating the activation of Akt.

PMID- 12803881
TI  - Continuous cardiac output and hemodynamic monitoring: high temporal correlation
      between plasma TNF-alpha and hemodynamic changes during a sepsis-like state in
      cancer immunotherapy.
AB  - Through continuous cardiac output monitoring, we investigated the temporal
      relationship between hemodynamic changes and plasma cytokines in a cancer patient
      who developed collateral sepsis to immunotherapy. A 52-year-old male with
      metastatic renal cell carcinoma received interleukin-2 (IL-2) infusion completing
      72 h of administration. The patient developed 3 sepsis-like states including
      systemic inflammatory response syndrome (SIRS), shock, and multiple organ
      dysfunction syndrome (MODS). Hemodynamic parameters including systemic vascular
      resistance index (SVRI), left ventricular stroke work index (LVSWI) and cardiac
      index (CI) were measured over 60 h. Peripheral blood was drawn when SVRI dropped
      20% in the patient and plasma cytokines including TNF-alpha, IL-6 and IL-1beta
      were measured using ELISA. After 60 h of immunotherapy, the patient showed a
      63.4% decrease in SVRI, 54.5% decrease in LVSWI and 65.4% increase in CI. The
      evaluation of systemic cytokines revealed different kinetic patterns: (i) a
      sustained increase in TNF-alpha levels through all 3 sepsis-like states; (ii) IL
      6 increased preferentially during SIRS and shock, while up/down-responses were
      found during MODS; (iii) IL-1beta was undetectable during the entire study
      period. A high temporal relationship between hemodynamic changes and plasma TNF
      alpha, but not IL-6, was found. Although there are factors other than cytokines
      that can alter vascular resistance, this finding could represent an approach to
      evaluate the course of hemodynamia and probably the systemic cytokine expression
      after IL-2 administration in renal cancer.

PMID- 12803882
TI  - Endotoxin boosts the vascular endothelial growth factor (VEGF) in rabbits.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine that greatly increases
      vascular permeability and thereby promotes hypovolemia. The present study
      examines whether the plasma VEGF concentration is increased by a bolus injection
      of endotoxin 20 microg/kg in 30 rabbits, and whether the response is modified by
      vitamin A, which doubles the endotoxin clearance. The results show that endotoxin
      stimulates a gradual increase in the VEGF concentration to a peak 5 h later which
      is approximately 100 times higher than the baseline concentration. No
      statistically significant difference was found between the rabbits that received
      no further treatment (n = 10) and the ones that were given 1000 IE/kg of vitamin
      A intravenously 1 h before (n = 10) or after (n = 10) the endotoxin. The rise in
      VEGF correlated with the development of fever, and the VEGF concentrations were
      higher in animals with a severely affected physical status as judged by the
      breathing pattern and changes in posture or reactivity. In conclusion, release of
      VEGF is part of the cytokine response to endotoxin with a peak occurring 5 h
      after a bolus injection, and the rise is pronounced also in the presence of a
      high endotoxin clearance.

PMID- 12803883
TI  - Endotoxin tolerance: is there a clinical relevance?
AB  - Beeson (1946) first defined endotoxin tolerance as a reduced endotoxin-induced
      fever following repeated injections of typhoid vaccine. Freudenberg and Galanos
      (1988) demonstrated that endotoxin tolerance that can protect against a lethal
      challenge of lipopolysaccharide (LPS) involves the participation of macrophages.
      Evans and Zuckerman (1991) reported a role for glucocorticoids in endotoxin
      tolerance. Prostaglandins, interleukin-(IL-)10, and transforming growth factor
      beta are other players of in vivo endotoxin tolerance. Dramatic reduction of
      plasma tumor necrosis factor (TNF) (Mathison et al. 1990) and other cytokines in
      response to LPS parallels endotoxin tolerance. The reduced capacity to produce
      TNF and other cytokines can be mimicked in vitro by pretreatment of monocytes or
      macrophages with LPS. It is not a specific phenomenon and can be induced by other
      agents or events. Cross-tolerance between LPS, TLR2 specific ligands, IL-1 and
      TNF has been regularly reported. A similar loss of LPS-reactivity has been
      repeatedly reported in leukocytes of septic patients and in patients with non
      infectious systemic inflammation response syndrome (SIRS; e.g. surgery, trauma,
      cardiac arrest and resuscitation, etc.). Studies on cellular signaling within
      leukocytes from septic and SIRS patients reveal numerous alterations of the
      activation pathways reminiscent of those observed in endotoxin-tolerant cells.
      While endotoxin tolerance prevents severity of infections and ischemia
      reperfusion damage, it has been suggested that the immune dysregulation observed
      in SIRS patients was associated with an enhanced sensitivity to nosocomial
      infections. In conclusion, in vitro and in vivo endotoxin tolerance, either
      experimental or due to clinical status, are similar but not identical.

PMID- 12803884
TI  - Differences in the mechanism of nitric oxide production between mouse vascular
      endothelial cells and macrophages.
AB  - The detailed mechanism of NO production in mouse vascular endothelial cells, END
      D, was studied. The NO production in END-D cells was triggered by gamma
      interferon (IFN-gamma), but not LPS. However, LPS augmented the NO production in
      IFN-gamma-stimulated END-D cells. A high level of NO production was due to the
      expression of an inducible type of NO synthase (iNOS) in those cells. A
      significant amount of NO was detected 18 h after IFN-gamma stimulation,
      accompanied by the delayed iNOS expression. The JAK/STAT signal pathway mediated
      IFN-gamma-induced NO production, but did not participate in the LPS-induced
      augmentation. Further, no activation of nuclear factor (NF)-kappaB was involved
      in the NO production in END-D cells stimulated with either IFN-gamma and/or LPS.
      The mechanism of NO production in END-D cells was suggested to be different from
      that in mouse macrophages. The differential regulation of NO production in mouse
      vascular endothelial cells and macrophages is discussed.

PMID- 12803885
TI  - Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and
      plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins.
AB  - Sepsis-induced changes in human plasma decrease LPS association with monocytes by
      regulating dynamic interactions among LPS, monocytes, and plasma lipoproteins. In
      the physiological environment of undiluted human serum, we have found that: (i)
      LPS binds transiently to monocytes and is released into plasma lipoproteins; (ii)
      the release of LPS from monocytes is dependent upon lipoprotein acceptors and is
      enhanced by soluble CD14 (sCD14); and (iii) both lipoproteins and sCD14 can
      attenuate cytokine responses in monocytes that have already bound LPS. Whereas
      LPS binding protein (LBP) also inhibited LPS responses after LPS had bound to
      monocytes, this did not require extensive release of cell-bound LPS as was
      observed with sCD14. In the serum of septic patients, both free LPS and monocyte
      bound LPS were usually transferred to lipoproteins at an accelerated rate. In
      spite of a sharp decline in HDL levels, HDL remained the dominant LPS acceptor in
      many severely septic patients, whereas in some cases LPS binding shifted largely
      to a non-HDL lipoprotein fraction that co-eluted according to size with very low
      density lipoprotein (VLDL). Preliminary data suggest that these lipoproteins have
      a very low density, and they contain apolipoprotein E and higher than normal
      proportions of the total lipoprotein cholesterol, phospholipid, apolipoprotein B,
      and serum amyloid A. The data suggest that the VLDL fraction contains acute phase
      lipoproteins of significantly altered composition that can replace HDL as the
      dominant LPS acceptor during sepsis when HDL levels are low.

PMID- 12803887
TI  - Lessons from an LPS-deficient Neisseria meningitidis mutant.
AB  - In the pathogen Neisseria meningitidis, a completely LPS-deficient but viable
      mutant can be obtained by insertional inactivation of the lpxA gene, encoding UDP
      GlcNAc acyltransferase required for the first step of lipid A biosynthesis. The
      expression and assembly of integral outer membrane proteins in the absence of LPS
      is largely unaffected. However, the expression of iron limitation-inducible, cell
      surface-exposed lipoproteins is greatly reduced. Major changes were seen in the
      phospholipid composition, with a shift towards PE and PG species containing
      mostly shorter chain, saturated fatty acids. The presence of the capsular
      polysaccharide turned out to be essential for viability without LPS. The
      immunogenicity of outer membrane proteins in mice was greatly reduced for the LPS
      deficient mutant, showing the importance of LPS as an internal adjuvant in such
      vaccines. Stimulation of MM6 cells and peripheral blood mononuclear cells showed
      that induction of TNF-alpha by whole meningococci was greatly reduced for the LPS
      deficient mutant. However, even without LPS the mutant strain could still induce
      a significant inflammatory response.

PMID- 12803886
TI  - Macrophage migration inhibitory factor (MIF) regulates host responses to
      endotoxin through modulation of Toll-like receptor 4 (TLR4).
AB  - The cytokine macrophage migration inhibitory factor (MIF) has emerged recently as
      an important mediator of inflammation and innate immunity. MIF is rapidly
      released by macrophages after stimulation with microbial products and pro
      inflammatory cytokines and, in turn, stimulates the production of pro
      inflammatory mediators by immune cells. Immunoneutralization of MIF or deletion
      of the Mif gene was shown to protect animals from lethal endotoxemia,
      staphylococcal toxic shock and septic shock in experimental models of bacterial
      peritonitis. To investigate the function of MIF in innate immunity, we studied
      the response of macrophages expressing reduced levels of MIF to microbial
      products. These cells were generated by transduction of an antisense MIF
      adenovirus or by stable transfection with an antisense MIF plasmid or were
      obtained from MIF-knockout mice. MIF-deficient macrophages were shown to be
      hyporesponsive to stimulation with LPS and Gram-negative bacteria. The defect was
      associated with a down-regulation of Toll-like receptor 4 (TLR4), the signal
      transducing molecule of the LPS receptor complex. Immunoneutralization of
      extracellular MIF decreased TLR4 expression and responses of macrophages to LPS,
      indicating that MIF may exert autocrine effects. These findings identify an
      important role for MIF in innate immunity and provide a rationale for the
      development of anti-MIF strategy for the treatment of patients with Gram-negative
      septic shock.

PMID- 12803888
TI  - Reproductive strategies in snakes.
AB  - Snakes of both sexes display remarkable flexibility and diversity in their
      reproductive tactics. Many features of reproduction in female snakes (such as
      reproductive mode and frequency, seasonality and multiple mating) allow flexible
      maternal control. For example, females can manipulate not only the genotypes of
      their offspring (through mate choice or enhanced sperm competition) but also the
      phenotypes of their offspring (through allocation 'decisions', behavioural and
      physiological thermoregulation, and nest-site selection). Reliance on stored
      energy ('capital') to fuel breeding results in low frequencies of female
      reproduction and, in extreme cases, semelparity. A sophisticated vomeronasal
      system not only allows male snakes to locate reproductive females by following
      scent trails, but also facilitates pheromonally mediated mate choice by males.
      Male-male rivalry takes diverse forms, including female mimicry and mate
      guarding; combat bouts impose strong selection for large body size in males of
      some species. Intraspecific (geographical) variation and phenotypic plasticity in
      a wide array of reproductive traits (offspring size and number; reproductive
      frequency; incidence of multiple mating; male tactics such as mate guarding and
      combat; mate choice criteria) provide exceptional opportunities for future
      studies.

PMID- 12803889
TI  - Evolution of sexual dimorphism in the olfactory brain of Hawaiian Drosophila.
AB  - In the fruitfly, Drosophila melanogaster, mate choice during courtship depends on
      detecting olfactory cues, sex pheromones, which are initially processed in the
      antennal lobe (AL), a primary olfactory centre of the brain. However, no sexual
      differences in the structure of the AL have been found in Drosophila. We compared
      the central brain anatomy of 37 species of Drosophilidae from the islands of the
      Hawaiian archipelago, uncovering an extreme sexual dimorphism within the AL in
      which two out of the 51 identifiable glomeruli were markedly enlarged in males. A
      phylogeny indicated that the sexual dimorphism of the homologous glomeruli arose
      0.4-1.9 Myr ago independently in two species groups of Hawaiian endemic
      Drosophilidae. The corresponding glomeruli in D. melanogaster were also found to
      be sexually dimorphic. The formation of glomeruli of male size is prevented by
      the ectopic expression of female-type transformer (tra) cDNA in males, indicating
      that the glomerular sexual dimorphism is under the control of the sex
      determination cascade of genes. It is suggested that a defined set of glomeruli
      in Drosophila can enlarge in response to sex-determination genetic signals, the
      mutations of which may result in species differences in sexual dimorphism of the
      brain.

PMID- 12803890
TI  - Evolution as a critical component of plankton dynamics.
AB  - Microevolution is typically ignored as a factor directly affecting ongoing
      population dynamics. We show here that density-dependent natural selection has a
      direct and measurable effect on a planktonic predator-prey interaction. We kept
      populations of Brachionus calyciflorus, a monogonont rotifer that exhibits
      cyclical parthenogenesis, in continuous flow-through cultures (chemostats) for
      more than 900 days. Initially, females frequently produced male offspring,
      especially at high population densities. We observed rapid evolution, however,
      towards low propensity to reproduce sexually, and by 750 days, reproduction had
      become entirely asexual. There was strong selection favouring asexual
      reproduction because, under the turbulent chemostat regime, males were unable to
      mate with females, produced no offspring, and so had zero fitness. In replicated
      chemostat experiments we found that this evolutionary process directly influenced
      the population dynamics. We observed very specific but reproducible plankton
      dynamics which are explained well by a mathematical model that explicitly
      includes evolution. This model accounts for both asexual and sexual reproduction
      and treats the propensity to reproduce sexually as a quantitative trait under
      selection. We suggest that a similar amalgam of ecological and evolutionary
      mechanisms may drive the dynamics of rapidly reproducing organisms in the wild.

PMID- 12803891
TI  - Functional consequences of genetic diversity in Strongyloides ratti infections.
AB  - Parasitic nematodes show levels of genetic diversity comparable to other taxa,
      but the functional consequences of this are not understood. Thus, a large body of
      theoretical work highlights the potential consequences of parasite genetic
      diversity for the epidemiology of parasite infections and its possible
      implications for the evolution of host and parasite populations. However, few
      relevant empirical data are available from parasites in general and none from
      parasitic nematodes in particular. Here, we test two hypotheses. First, that
      different parasitic nematode genotypes vary in life-history traits, such as
      survivorship and fecundity, which may cause variation in infection dynamics.
      Second, that different parasitic nematode genotypes interact within the host
      (either directly or via the host immune system) to increase the mean reproductive
      output of mixed-genotype infections compared with single-genotype infections. We
      test these hypotheses in laboratory infections using genetically homogeneous
      lines of Strongyloides ratti. We find that nematode genotypes do vary in their
      survivorship and fecundity and, consequently, in their dynamics of infection.
      However, we find little evidence of interactions between genotypes within hosts
      under a variety of trickle- and single-infected infection regimes.

PMID- 12803892
TI  - Melanic body colour and aggressive mating behaviour are correlated traits in male
      mosquitofish (Gambusia holbrooki).
AB  - Correlated traits are important from an evolutionary perspective as natural
      selection acting on one trait may indirectly affect other traits. Further, the
      response to selection can be constrained or hastened as a result of correlations.
      Because mating behaviour and body colour can dramatically affect fitness, a
      correlation between them can have important fitness ramifications. In this work,
      melanic (black) male mosquitofishes (Gambusia holbrooki) with temperature
      sensitive body-colour expression are bred in captivity. Half of the sons of each
      melanic sire are reared at 19 degrees C (and express a black body colour) and
      half are reared at 31 degrees C (and express a silver body colour). The two
      colour morphs are placed in the same social setting and monitored for behavioural
      differences. Mating behaviour and colour are correlated traits. Mating behaviour
      differs markedly between the two phenotypes, despite high genetic relatedness.
      Melanic (black) phenotypes are more aggressive towards females, chasing them and
      attempting more matings than their silver siblings. Females avoid melanic-male
      mating attempts more than silver-male mating attempts. When males with
      temperature-sensitive colour expression are melanic and aggressive, they probably
      experience a very different selective regime in nature from when they are silver
      and less aggressive. Under some conditions (e.g. predation), melanic coloration
      and/or aggression is advantageous compared with silver coloration and/or less
      aggressive behaviour. However, under different conditions (e.g. high-frequency
      melanism), melanism and/or aggression appears to be disadvantageous and melanic
      males have reduced survival and reproduction. Selective advantages to each morph
      under different conditions may enable the long-term persistence of this
      temperature-sensitive genotype.

PMID- 12803893
TI  - From individual control to majority rule: extending transactional models of
      reproductive skew in animal societies.
AB  - Transactional concession models of social evolution explain the reproductive skew
      within groups by assuming that a dominant individual completely controls the
      allocation of reproduction to other group members. The models predict when the
      dominant will benefit from donating parcels of reproduction to other members in
      return for peaceful cooperation. Using linear programming methods, we present a
      'majority-rules' model in which the summed actions of all society members, each
      with equal power, completely determine the reproductive share of any single
      member. The majority-rules model predicts that, despite the diffusion of power, a
      'virtual dominant' (a dominant lacking special behavioural power) will emerge and
      that the reproductive skew will be exactly that predicted if the virtual dominant
      were to control completely the group's reproductive partitioning. The virtual
      dominant is the individual to which group members have the maximum average
      genetic relatedness. This result greatly broadens the applicability of
      transactional models of reproductive skew to social groups of any size, such as
      large-colony eusocial insects, and explains why queens in such colonies can
      achieve reproductive domination without any behavioural enforcement. Moreover,
      the majority-rules model unifies transactional-skew theory with models of worker
      policing and even generates a new theory for the cooperation among somatic cells
      in a multicellular organism.

PMID- 12803894
TI  - Augmented discounting: interaction between ageing and time-preference behaviour.
AB  - Discounting occurs when an immediate benefit is systematically valued more highly
      than a delayed benefit of the same magnitude. It is manifested in physiological
      and behavioural strategies of organisms. This study brings together life-history
      theory and time-preference theory within a single modelling framework. We
      consider an animal encountering reproductive opportunities as a random process.
      Under an external hazard, optimal life-history strategy typically prioritizes
      immediate reproduction at the cost of declining fertility and increasing
      mortality with age. Given such ageing, an immediate reproductive reward should be
      preferred to a delayed reward because of both the risk of death and declining
      fertility. By this analysis, ageing is both a consequence of discounting by the
      body and a cause of behavioural discounting. A series of models is developed,
      making different assumptions about external hazards and biological ageing. With
      realistic ageing assumptions (increasing mortality and an accelerating rate of
      fertility decline) the time-preference rate increases in old age. Under an
      uncertain external hazard rate, young adults should also have relatively high
      time-preference rates because their (Bayesian) estimate of the external hazard is
      high. Middle-aged animals may therefore be the most long term in their outlook.

PMID- 12803895
TI  - The limits to cost-free signalling of need between relatives.
AB  - Theoretical models have demonstrated the possibility of stable cost-free
      signalling of need between relatives. The stability of these cost-free equilibria
      depends on the indirect fitness cost of cheating and deceiving a donor into
      giving away resources. We show that this stability is highly sensitive to the
      distribution of need among signallers and receivers. In particular, cost-free
      signalling is likely to prove stable only if there is very large variation in
      need (such that the least-needy individuals stand to gain much less than the most
      needy individuals from additional resources). We discuss whether these conditions
      are likely to be found in altricial avian breeding systems--the most intensively
      studied instance of signalling of need between relatives. We suggest that cost
      free signalling is more likely to prove stable and will provide parents with more
      information during the earlier phases of chick growth, when parents can more
      easily meet the demands of a brood (and chicks are more likely to reach
      satiation). Later, informative yet cost-free signalling is unlikely to persist.

PMID- 12803897
TI  - Good foragers can also be good at detecting predators.
AB  - The degree to which foraging and vigilance are mutually exclusive is crucial to
      understanding the management of the predation and starvation risk trade-off in
      animals. We tested whether wild-caught captive chaffinches that feed at a higher
      rate do so at the expense of their speed in responding to a model sparrowhawk
      flying nearby, and whether consistently good foragers will therefore tend to
      respond more slowly on average. First, we confirmed that the time taken to
      respond to the approaching predator depended on the rate of scanning: as head-up
      rate increased so chaffinches responded more quickly. However, against
      predictions, as peck rate increased so head-up rate increased and mean length of
      head-up and head-down periods decreased. Head-up rate was probably dependent on
      peck rate because almost every time a seed was found, a bird raised its head to
      handle it. Therefore chaffinches with higher peck rates responded more quickly.
      Individual chaffinches showed consistent durations of both their head-down and
      head-up periods and, therefore, individuals that were good foragers were also
      good detectors of predators. In relation to the broad range of species that have
      a similar foraging mode to chaffinches, our results have two major implications
      for predation/starvation risk trade-offs: (i) feeding rate can determine
      vigilance scanning patterns; and (ii) the best foragers can also be the best at
      detecting predators. We discuss how our results can be explained in mechanistic
      terms relating to fundamental differences in how the probabilities of detecting
      food rather than a predator are affected by time. In addition, our results offer
      a plausible explanation for the widely observed effect that vigilance continues
      to decline with group size even when there is no further benefit to reducing
      vigilance.

PMID- 12803896
TI  - Lizard threat display handicaps endurance.
AB  - Honest-signalling theory asserts that threat displays reliably advertise
      attributes that influence fighting success. Endurance, as measured by treadmill
      performance, predicts the outcome of agonistic interactions among lizards. If
      threat displays in lizards function to advertise endurance capacity then
      variation in threat displays should correlate with endurance. I tested this
      prediction for the duration of threat posturing in male side-blotched lizards
      (Uta stansburiana) and examined whether threat displays act as quality handicaps,
      reliable signals that expend the attribute that is advertised. Individual
      variation in the duration of threat posturing correlated with endurance, while an
      experimental reduction of endurance diminished the duration of threat posturing.
      As expected of a quality handicap, endurance fell below baseline after display
      production. A restriction of aerobic metabolism can account for this effect. In
      threat posturing, lateral compression of the thorax may interfere with
      respiration or with circulation, limiting aerobic metabolism and causing a
      compensatory increase in anaerobic metabolism, thereby generating lactate and
      diminishing locomotor capacity. Concentrations of lactate measured after display
      production were higher than baseline, consistent with the proposed mechanism. By
      restricting aerobic metabolism, the threat posture can act as a quality handicap,
      simultaneously advertising and expending the endurance capacity of displaying
      lizards.

PMID- 12803898
TI  - Combined large and small subunit ribosomal RNA phylogenies support a basal
      position of the acoelomorph flatworms.
AB  - The phylogenetic position of the phylum Platyhelminthes has been re-evaluated in
      the past decade by analysis of diverse molecular datasets. The consensus is that
      the Rhabditophora + Catenulida, which includes most of the flatworm taxa, are not
      primitively simple basal bilaterians but are related to coelomate phyla such as
      molluscs. The status of two other groups of acoelomate worms, Acoela and
      Nemertodermatida, is less clear. Although many characteristics unite these two
      groups, initial molecular phylogenetic studies placed the Nemertodermatida within
      the Rhabditophora, but placed the Acoela at the base of the Bilateria, distant
      from other flatworms. This contradiction resulted in scepticism about the basal
      position of acoels and led to calls for further data. We have sequenced large
      subunit ribosomal RNA genes from 13 rhabditophorans + catenulids, three acoels
      and one nemertodermatid, tripling the available data. Our analyses strongly
      support a basal position of both acoels and nemertodermatids. Alternative
      hypotheses are significantly less well supported by the data. We conclude that
      the Nemertodermatida and Acoela are basal bilaterians and, owing to their unique
      body plan and embryogenesis, should be recognized as a separate phylum, the
      Acoelomorpha.

PMID- 12803899
TI  - Long-time storage of song types in birds: evidence from interactive playbacks.
AB  - In studies of birdsong learning, imitation-based assays of stimulus memorization
      do not take into account that tutored song types may have been stored, but were
      not retrieved from memory. Such a 'silent' reservoir of song material could be
      used later in the bird's life, e.g. during vocal interactions. We examined this
      possibility in hand-reared nightingales during their second year. The males had
      been exposed to songs, both as fledglings and later, during their first full song
      period in an interactive playback design. Our design allowed us to compare the
      performance of imitations from the following categories: (i) songs only
      experienced during the early tutoring; (ii) songs experienced both during early
      tutoring and interactive playbacks; and (iii) novel songs experienced only during
      the simulated interactions. In their second year, birds imitated song types from
      each category, including those from categories (i) and (ii) which they had failed
      to imitate before. In addition, the performance of these song types was different
      (category (ii) > category (i)) and more pronounced than for category (iii) songs.
      Our results demonstrate 'silent' song storage in nightingales and point to a
      graded influence of the time and the social context of experience on subsequent
      vocal imitation.

PMID- 12803900
TI  - Rates of species introduction to a remote oceanic island.
AB  - The introduction of species to areas beyond the limits of their natural
      distributions has a major homogenizing influence, making previously distinct
      biotas more similar. The scale of introductions has frequently been commented on,
      but their rate and spatial pervasiveness have been less well quantified. Here, we
      report the findings of a detailed study of pterygote insect introductions to
      Gough Island, one of the most remote and supposedly pristine temperate oceanic
      islands, and estimate the rate at which introduced species have successfully
      established. Out of 99 species recorded from Gough Island, 71 are established
      introductions, the highest proportion documented for any Southern Ocean island.
      Estimating a total of approximately 233 landings on Gough Island since first
      human landfall, this equates to one successful establishment for every three to
      four landings. Generalizations drawn from other areas suggest that this may be
      only one-tenth of the number of pterygote species that have arrived at the
      island, implying that most landings may lead to the arrival of at least one
      alien. These rates of introduction of new species are estimated to be two to
      three orders of magnitude greater than background levels for Gough Island, an
      increase comparable to that estimated for global species extinctions (many of
      which occur on islands) as a consequence of human activities.

PMID- 12803901
TI  - Punishment and reputation in spatial public goods games.
AB  - The puzzle of the emergence of cooperation between unrelated individuals is
      shared across diverse fields of behavioural sciences and economics. In this
      article we combine the public goods game originating in economics with
      evolutionary approaches traditionally used in biology. Instead of pairwise
      encounters, we consider the more complex case of groups of three interacting
      individuals. We show that territoriality is capable of promoting cooperative
      behaviour, as in the case of the Prisoner's Dilemma. Moreover, by adding
      punishment opportunities, the readiness to cooperate is greatly enhanced and
      asocial strategies can be largely suppressed. Finally, as soon as players carry a
      reputation for being willing or unwilling to punish, highly cooperative and fair
      outcomes are achieved. This group-beneficial result is obtained, intriguingly, by
      making individuals more likely to exploit their co-players if they can get away
      with it. Thus, less-cooperative individuals make more-cooperative societies.

PMID- 12803902
TI  - Structural rRNA characters support monophyly of raptorial limbs and paraphyly of
      limb specialization in water fleas.
AB  - The evolutionary success of arthropods has been attributed partly to the
      diversity of their limb morphologies. Large morphological diversity and increased
      specialization are observed in water flea (Cladocera) limbs, but it is unclear
      whether the increased limb specialization in different cladoceran orders is the
      result of shared ancestry or parallel evolution. We inferred a robust among-order
      cladoceran phylogeny using small-subunit and large-subunit rRNA nuclear gene
      sequences, signature sequence regions, novel stem-loops and secondary structure
      morphometrics to assess the phylogenetic distribution of limb specialization. The
      sequence-based and structural rRNA morphometric phylogenies were congruent and
      suggested monophyly of orders with raptorial limbs, but paraphyly of orders with
      reduced numbers of specialized limbs. These results highlight the utility of
      complex molecular structural characters in resolving ancient rapid radiations.

PMID- 12803903
TI  - A private ultraviolet channel in visual communication.
AB  - Although private communication is considered an important diversifying force in
      evolution, there is little direct behavioural evidence to support this notion.
      Here, we show that ultraviolet (UV) signalling in northern swordtails
      (Xiphophorus) affords a channel for communication that is not accessible to their
      major predator, Astyanax mexicanus, the Mexican tetra. Laboratory and field
      behavioural experiments with swordtails (X. nigrensis) and predators (A.
      mexicanus) demonstrate that male UV ornamentation significantly increases their
      attractiveness to females but not to this predator, which is less sensitive to
      UV. UV reflectance among swordtail species correlates positively with tetra
      densities across habitats, and visual contrast estimates suggest that UV signals
      are highly conspicuous to swordtails in their natural environment. Cross-species
      comparisons also support the hypothesis that natural selection drives the use of
      UV communication. We compared two species, one with high (X. nigrensis) and one
      with low (X. malinche) Mexican tetra densities. Xiphophorus nigrensis males
      reflect significantly more UV than X. malinche, exhibit significant UV sexual
      dimorphism, and UV is a salient component of the sexual communication system. In
      X. malinche, however, males reflect minimally in the UV, there is no UV sexual
      dimorphism, and UV does not play a part in its communication system.

PMID- 12803904
TI  - Reductions in total body fat decrease humoral immunity.
AB  - Mounting an immune response requires substantial energy, and it is well known
      that marked reductions in energy availability (e.g. starvation) can suppress
      immune function, thus increasing disease susceptibility and compromising
      survival. We tested the hypothesis that moderate reductions in energy
      availability impair humoral immunity. Specifically, we examined the effects of
      partial lipectomy (LIPx) on humoral immunity in two seasonally breeding rodent
      species, prairie voles (Microtus ochrogaster) and Siberian hamsters (Phodopus
      sungorus). Animals received bilateral surgical removal of epididymal white
      adipose tissue (EWATx), inguinal white adipose tissue (IWATx) or sham surgeries
      and were injected with the antigen keyhole limpet haemocyanin (KLH) either four
      or 12 weeks after surgery. In prairie voles, serum anti-KLH immunoglobulin G
      (IgG) did not differ significantly at four weeks. At 12 weeks, serum IgG was
      significantly reduced in IWATx, but not EWATx animals, compared with sham
      operated animals. In Siberian hamsters, both IWATx and EWATx animals reduced
      serum IgG at four weeks. At 12 weeks, EWATx hamsters displayed a significant
      compensatory increase in IWAT pad mass compared with sham-operated hamsters, and
      serum IgG no longer differed from sham-operated animals. There was no significant
      increase in EWAT in IWATx hamsters compared with sham animals and IgG remained
      significantly reduced in IWATx hamsters. These results suggest that reductions in
      energy availability can impair humoral immunity.

PMID- 12803905
TI  - Expanding comparative-advantage biological market models: contingency of
      mutualism on partners' resource requirements and acquisition trade-offs.
AB  - We expand the comparative-advantage biological market-modelling framework to show
      how differences between partners, both in their abilities to acquire two
      resources and in their requirements for those resources, can affect the net
      benefit of participating in interspecific resource exchange. In addition, the
      benefits derived from resource trading depend strongly on the nature of the trade
      off between the acquisition of one resource and the acquisition of another,
      described here by the shape (linear, convex or concave) of the resource
      acquisition constraints of the individuals involved. Combined with previous
      results, these analyses provide a suite of predictions about whether or not
      resource exchange is beneficial for two heterospecific individuals relative to a
      strategy of non-interaction. The benefit derived from resource exchange depends
      on three factors: (i) relative differences between the partners in their resource
      acquisition abilities; (ii) relative differences between the partners in their
      resource requirements; and (iii) variation in the shape of resource acquisition
      trade-offs. We find that such an explicit consideration of resource requirements
      and acquisition abilities can provide useful and sometimes non-intuitive
      predictions about the benefits of resource exchange, and also which resources
      should be traded by which species.

PMID- 12803906
TI  - Site-specific selfish genes as tools for the control and genetic engineering of
      natural populations.
AB  - Site-specific selfish genes exploit host functions to copy themselves into a
      defined target DNA sequence, and include homing endonuclease genes, group II
      introns and some LINE-like transposable elements. If such genes can be engineered
      to target new host sequences, then they can be used to manipulate natural
      populations, even if the number of individuals released is a small fraction of
      the entire population. For example, a genetic load sufficient to eradicate a
      population can be imposed in fewer than 20 generations, if the target is an
      essential host gene, the knockout is recessive and the selfish gene has an
      appropriate promoter. There will be selection for resistance, but several
      strategies are available for reducing the likelihood of it evolving. These genes
      may also be used to genetically engineer natural populations, by means of
      population-wide gene knockouts, gene replacements and genetic transformations. By
      targeting sex-linked loci just prior to meiosis one may skew the population sex
      ratio, and by changing the promoter one may limit the spread of the gene to
      neighbouring populations. The proposed constructs are evolutionarily stable in
      the face of the mutations most likely to arise during their spread, and
      strategies are also available for reversing the manipulations.

PMID- 12803907
TI  - The scent of age.
AB  - In many species, older males are often preferred mates because they carry 'good'
      genes that account for their viability. How females discern a male's age is a
      matter of question. However, for animals that rely heavily on chemical
      communication there is some indication that an animal's age can be determined by
      its scent. To investigate whether there are changes in body odours with age, and
      if so their composition, mice were trained in a Y-maze to discriminate urine
      odours of donor mice of different ages: Adult (3-10 months old) and Aged (more
      than 17 months old). Trained mice could discriminate between these two age groups
      by odour alone. To determine the chemical basis for these discriminations,
      studies were performed using gas chromatography and mass spectrometry. These
      analyses demonstrated differences in the ratio of urinary volatiles with age. The
      most prominent differences involved significantly greater amounts of 2
      phenylacetamide and significantly lower amounts of methylbutyric acids in Aged
      animals relative to Adult animals. Fractionating and manipulating the levels of
      these compounds in the urine demonstrated that the mice can distinguish age based
      on variation in amounts of these specific compounds in the combined urine.

PMID- 12803908
TI  - Phenotypically plastic adjustment of sex allocation in a simultaneous
      hermaphrodite.
AB  - Sex allocation theory for simultaneous hermaphrodites predicts an influence of
      the mating group size on sex allocation. Mating group size may depend on the size
      of the group in which an individual lives, or on the density, but studies to date
      have not distinguished between the two factors. We performed an experiment in
      which we raised a transparent simultaneous hermaphrodite, the flatworm
      Macrostomum sp., in different group sizes (pairs, triplets, quartets and octets)
      and in different enclosure sizes (small and large). This design allows us to
      differentiate between the effects of group size and density. After worms reached
      maturity we determined their reproductive allocation patterns from microscopic
      images taken in vivo. The results suggest that the mating group size is a
      function of the group size, and not of the density. They support the shift to
      higher male allocation in larger mating groups predicted by sex allocation
      theory. To our knowledge, this is the first study that unambiguously shows
      phenotypically plastic sex allocation in response to mating group size in a
      simultaneous hermaphrodite.

PMID- 12803909
TI  - Sexual growth dimorphism affects birth sex ratio in house mice.
AB  - We present the first empirical evidence that mammalian sex-ratio deviations
      result from variation in adult-weight sexual dimorphism via correlated effects on
      blastocyst development. Two selection lines of mice exhibiting high and low
      sexual dimorphism in adult weight showed correlated sexual weight differences at
      birth and at weaning, caused by relatively decelerated growth of males in the low
      line from before birth. The sex ratio at birth was significantly female-biased in
      the low line, and significantly lower than in the highly dimorphic line.
      Concomitantly, blastomere numbers were at significantly higher variance in the
      low than in the highly dimorphic line, owing to an increased frequency of slowly
      growing blastocysts. Since low-dimorphism mice produced more corpora lutea and
      more female pups than the high-dimorphism mice, but not more males, birth sex
      ratio bias most parsimoniously resulted from the loss of slowly growing male
      blastocysts. This is in agreement with the observation that sex-ratio skews in
      mammals arise when timing of uterine responsiveness (i.e. its temporally limited
      capacity for implantation) varies in relation to sex-specific embryonic growth
      rates. Hence, natural mammalian sex-ratio variation that stems from developmental
      asynchrony might be a by-product of natural selection for sexual dimorphism in
      adult weight.

PMID- 12803910
TI  - Frequency-dependent variation in reproductive success in Narcissus: implications
      for the maintenance of stigma-height dimorphism.
AB  - Negative frequency-dependent selection is a major selective force maintaining
      sexual polymorphisms. However, empirical demonstrations of frequency-dependent
      reproductive success are rare, particularly in plants. We investigate this
      problem by manipulating the frequencies of style morphs in a natural population
      of Narcissus assoanus, a self-incompatible herb with style-length dimorphism and
      intra-morph compatibility. We predicted that the reproductive success of morphs
      would vary negatively with their frequency because of the effects of morph
      specific differences in sex-organ position on patterns of pollen transfer. This
      prediction was generally supported. The fruit and seed set of the two morphs did
      not differ significantly in plots with 1 : 1 morph ratios. However, short-styled
      plants produced significantly fewer seeds than long-styled plants in monomorphic
      plots, and significantly more seeds than long-styled plants in plots with 'long
      biased' morph ratios. These patterns indicate that in the absence of
      physiological barriers to intra-morph mating, negative frequency-dependent
      selection contributes to the maintenance of stylar polymorphism through inter
      morph pollen transfer. Our experimental results also provide insights into the
      mechanisms governing the biased style-morph ratios in populations of Narcissus
      species.

PMID- 12803911
TI  - Fruit set of highland coffee increases with the diversity of pollinating bees.
AB  - The worldwide decline of pollinators may negatively affect the fruit set of wild
      and cultivated plants. Here, we show that fruit set of the self-fertilizing
      highland coffee (Coffea arabica) is highly variable and related to bee
      pollination. In a comparison of 24 agroforestry systems in Indonesia, the fruit
      set of coffee could be predicted by the number of flower-visiting bee species,
      and it ranged from ca. 60% (three species) to 90% (20 species). Diversity, not
      abundance, explained variation in fruit set, so the collective role of a species
      rich bee community was important for pollination success. Additional experiments
      showed that single flower visits from rare solitary species led to higher fruit
      set than with abundant social species. Pollinator diversity was affected by two
      habitat parameters indicating guild-specific nesting requirements: the diversity
      of social bees decreased with forest distance, whereas the diversity of solitary
      bees increased with light intensity of the agroforestry systems. These results
      give empirical evidence for a positive relationship between ecosystem functions
      such as pollination and biodiversity. Conservation of rainforest adjacent to
      adequately managed agroforestry systems could improve the yields of farmers.

PMID- 12803912
TI  - Forest management is associated with physiological stress in an old-growth forest
      passerine.
AB  - We investigated how physiological stress in an area-sensitive old-growth forest
      passerine, the Eurasian treecreeper (Certhia familiaris), is associated with
      forest fragmentation and forest structure. We found evidence that the
      concentrations of plasma corticosterone in chicks were higher under poor food
      supply in dense, young forests than in sparse, old forests. In addition,
      nestlings in large forest patches had lower corticosterone levels and a better
      body condition than in small forest patches. In general, corticosterone levels
      were negatively related to body condition and survival. We also found a decrease
      in corticosterone levels within the breeding season, which may have been a result
      of an increase in food supply from the first to the second broods. Our results
      suggest that forest fragmentation may decrease the fitness of free-living
      individual treecreepers.

PMID- 12803913
TI  - Colony insularity through queen control on worker social motivation in ants.
AB  - We investigated the relative contribution of the queen and workers to colony
      nestmate recognition cues and on colony insularity in the Carpenter ant
      Camponotus fellah. Workers were either individually isolated, preventing contact
      with both queen and workers (colonial deprived, CD), kept in queenless groups,
      allowing only worker-worker interactions (queen deprived, QD) or in queenright
      (QR) groups. Two weeks post-separation QD and QR workers were amicable towards
      each other but both rejected their CD nestmates, which suggests that the queen
      does not measurably influence the colony recognition cues. By contrast,
      aggression between QD and QR workers from the same original colony was apparent
      only after six months of separation. This clearly demonstrates the power of the
      Gestalt and indicates that the queen is not a dominant contributor to the
      nestmate recognition cues in this species. Aggression between nestmates was
      correlated with a greater hydrocarbon (HC) profile divergence for CD than for QD
      and QR workers, supporting the importance of worker-worker interactions in
      maintaining the colony Gestalt odour. While the queen does not significantly
      influence nestmate recognition cues, she does influence colony insularity since
      within 3 days QD (queenless for six months) workers from different colony origins
      merged to form a single queenless colony. By contrast, the corresponding QR
      colonies maintained their territoriality and did not merge. The originally
      divergent cuticular and postpharyngeal gland HC profiles became congruent
      following the merger. Therefore, while workers supply and blend the recognition
      signal, the queen affects worker-worker interaction by reducing social motivation
      and tolerance of alien conspecifics.

PMID- 12803914
TI  - Unravelling dispersal patterns in an expanding population of a highly mobile
      seabird, the northern fulmar (Fulmarus glacialis).
AB  - The northern fulmar (Fulmarus glacialis) is an abundant seabird whose Northeast
      Atlantic population has expanded dramatically over the past 100 years.
      Archaeological evidence suggests that Iceland and St Kilda were the ancestral
      populations from which essentially all other colonies in the region were derived.
      We collected samples from seven breeding colonies around the North Atlantic and
      used mitochondrial DNA analysis to ask whether population structure was present
      and, if so, where there was evidence about which colony was the dominant source
      population. Our data reveal a pattern consistent with isolation by distance,
      suggesting that, even though capable of flying great distances, most birds return
      to breed either at their own or neighbouring colonies. Interestingly, although
      most colonizers appear to have come originally from Iceland, our analysis also
      identifies St Kilda as a possible source. However, this secondary pattern appears
      to be largely an artefact, and can be attributed to the low haplotype diversity
      on St Kilda which yields a much clearer isolation by distance signal than that
      generated by birds dispersing from Iceland, where haplotype diversity is
      extremely high. Consequently, we urge caution when interpreting patterns in which
      populations vary greatly in the genetic diversity they harbour.

PMID- 12803915
TI  - The last dicynodont: an Australian Cretaceous relict.
AB  - Some long-forgotten fossil evidence reveals that a dicynodont (mammal-like
      reptile of the infraorder Dicynodontia) inhabited Australia as recently as the
      Early Cretaceous, ca. 110 Myr after the supposed extinction of dicynodonts in the
      Late Triassic. This remarkably late occurrence more than doubles the known
      duration of dicynodont history (from ca. 63 Myr to ca. 170 Myr) and betrays the
      profound impact of geographical isolation on Australian terrestrial faunas
      through the Mesozoic. Australia's late-surviving dicynodont may be envisaged as a
      counterpart of the ceratopians (horned dinosaurs) in Cretaceous tetrapod faunas
      of Asia and North America.

PMID- 12803918
TI  - Formation of functional cell membrane domains: the interplay of lipid- and
      protein-mediated interactions.
AB  - Numerous cell membrane associated processes, including signal transduction,
      membrane sorting, protein processing and virus trafficking take place in membrane
      subdomains. Protein-protein interactions provide the frameworks necessary to
      generate biologically functional membrane domains. For example, coat proteins
      define membrane areas destined for sorting processes, viral proteins self
      assemble to generate a budding virus, and adapter molecules organize
      multimolecular signalling assemblies, which catalyse downstream reactions. The
      concept of raft lipid-based membrane domains provides a different principle for
      compartmentalization and segregation of membrane constituents. Accordingly, rafts
      are defined by the physical properties of the lipid bilayer and function by
      selective partitioning of membrane lipids and proteins into membrane domains of
      specific phase behaviour and lipid packing. Here, I will discuss the interplay of
      these independent principles of protein scaffolds and raft lipid microdomains
      leading to the generation of biologically functional membrane domains.

PMID- 12803917
TI  - Biosynthesis and degradation of mammalian glycosphingolipids.
AB  - Glycolipids are a large and heterogeneous family of sphingolipids that form
      complex patterns on eukaryotic cell surfaces. This molecular diversity is
      generated by only a few enzymes and is a paradigm of naturally occurring
      combinatorial synthesis. We report on the biosynthetic principles leading to this
      large molecular diversity and focus on sialic acid-containing glycolipids of the
      ganglio-series. These glycolipids are particularly concentrated in the plasma
      membrane of neuronal cells. Their de novo synthesis starts with the formation of
      the membrane anchor, ceramide, at the endoplasmic reticulum (ER) and is continued
      by glycosyltransferases of the Golgi complex. Recent findings from genetically
      engineered mice are discussed. The constitutive degradation of glycosphingolipids
      (GSLs) occurs in the acidic compartments, the endosomes and the lysosomes. Here,
      water-soluble glycosidases sequentially cleave off the terminal carbohydrate
      residues from glycolipids. For glycolipid substrates with short oligosaccharide
      chains, the additional presence of membrane-active sphingolipid activator
      proteins (SAPs) is required. A considerable part of our current knowledge about
      glycolipid degradation is derived from a class of human diseases, the
      sphingolipidoses, which are caused by inherited defects within this pathway. A
      new post-translational modification is the attachment of glycolipids to proteins
      of the human skin.

PMID- 12803919
TI  - The fate and function of glycosphingolipid glucosylceramide.
AB  - In higher eukaryotes, glucosylceramide is the simplest member and precursor of a
      fascinating class of membrane lipids, the glycosphingolipids. These lipids
      display an astounding variation in their carbohydrate head groups, suggesting
      that glycosphingolipids serve specialized functions in recognition processes. It
      is now realized that they are organized in signalling domains on the cell
      surface. They are of vital importance as, in their absence, embryonal development
      is inhibited at an early stage. Remarkably, individual cells can live without
      glycolipids, perhaps because their survival does not depend on glycosphingolipid
      mediated signalling mechanisms. Still, these cells suffer from defects in
      intracellular membrane transport. Various membrane proteins do not reach their
      intracellular destination, and, indeed, some intracellular organelles do not
      properly differentiate to their mature stage. The fact that glycosphingolipids
      are required for cellular differentiation suggests that there are human diseases
      resulting from defects in glycosphingolipid synthesis. In addition, the same
      cellular differentiation processes may be affected by defects in the degradation
      of glycosphingolipids. At the cellular level, the pathology of glycosphingolipid
      storage diseases is not completely understood. Cell biological studies on the
      intracellular fate and function of glycosphingolipids may open new ways to
      understand and defeat not only lipid storage diseases, but perhaps other diseases
      that have not been connected to glycosphingolipids so far.

PMID- 12803920
TI  - Generation of CD1 tetramers as a tool to monitor glycolipid-specific T cells.
AB  - CD1 molecules are beta(2)m-associated HLA class-I-like glycoproteins which have
      the unique ability to present glycolipid and phospholipid antigens to specific T
      lymphocytes. To study the biology of CD1 and its role in human disease we
      developed novel techniques for generation of recombinant CD1/lipid complexes by
      in vitro refolding. Fluorescent tetrameric complexes made from soluble
      recombinant CD1d/alpha-galactosylceramide complexes allowed highly sensitive and
      specific ex vivo and in vitro detection and functional characterization of novel
      human T-lymphocyte populations. Furthermore, protein crystals were obtained from
      soluble recombinant CD1b/beta(2)m-proteins loaded either with
      phosphatidylinositol or ganglioside GM2, which led to the first atomic structure
      determination of a CD1/lipid complex. The analysis of these crystal structures
      clarified how CD1b molecules can bind lipid ligands of different size, and
      revealed a broader spectrum of potential CD1b ligands than previously predicted.

PMID- 12803921
TI  - Glycosphingolipid functions: insights from engineered mouse models.
AB  - Glycosphingolipids are remarkable for their structural complexity and their
      distinctive patterns that mark different tissues and stages of development. The
      physiological functions of glycosphingolipids are likely to be profound and are
      only beginning to emerge. Much of this new information is due to the study of
      mutant mice lacking specific sets of glycosphingolipids, the topic of this
      review.

PMID- 12803922
TI  - Endocytic trafficking of glycosphingolipids in sphingolipid storage diseases.
AB  - In this review, recent studies of membrane lipid transport in sphingolipid (SL)
      storage disease (SLSD) fibroblasts are summarized. Several fluorescent
      glycosphingolipid (GSL) analogues are internalized from the plasma membrane via
      caveolae and are subsequently transported to the Golgi complex of normal
      fibroblasts, while in 10 different SLSD cell types, these lipids accumulate in
      endosomes and lysosomes. Additional studies have shown that cholesterol
      homeostasis is perturbed in multiple SLSDs secondary to accumulation of
      endogenous SLs, and that mis-targeting of the GSLs is regulated by cellular
      cholesterol. Golgi targeting of GSLs internalized via caveolae is dependent on
      microtubules and phosphoinositide 3-kinase(s) and is inhibited by expression of
      dominant-negative rab7 and rab9 constructs. Overexpression of wild-type rab7 or
      rab9 (but not rab11) in Niemann-Pick C fibroblasts results in correction of lipid
      trafficking defects, including restoration of Golgi targeting of fluorescent
      lactosylceramide and endogenous GM1 ganglioside (monitored by the transport of
      fluorescent cholera toxin), and a dramatic reduction in accumulation of
      intracellular cholesterol. These results suggest an approach for restoring normal
      lipid trafficking in this, and perhaps other, SLSD cell types, and may provide a
      basis for future therapy of these diseases.

PMID- 12803923
TI  - Neurobiology and cellular pathogenesis of glycolipid storage diseases.
AB  - Disorders of lysosomal metabolism often involve the accumulation of specific
      types of glycolipid, particularly gangliosides, because of either degradative
      failure or other currently unknown mechanisms. Although the precise role of
      gangliosides in cells remains enigmatic, the presence of specific abnormalities
      secondary to ganglioside accumulation in lysosomal diseases has suggested
      important biological functions. Chief among these is the growth of new dendrites
      on particular classes of mature neurons secondary to an increase in GM2
      ganglioside. That GM2 has also been shown to be elevated in normal immature
      neurons coincident with dendritic sprouting provides a compelling argument that
      this ganglioside plays a role in dendritic initiation. This discovery has led to
      the search for other regulators of dendritic differentiation that may in some way
      be linked to the expression and/or function of GM2 ganglioside. Principal
      candidates that have emerged include tyrosine kinase receptors, small GTPases and
      calcium/calmodulin-dependent protein kinase II. Understanding the mechanism
      underlying ectopic dendritogenesis in lysosomal diseases can be expected to
      generate significant insight into the control of dendritic plasticity in normal
      brain. The detrimental aspects of ganglioside accumulation in storage diseases as
      well as the potential link between gangliosides and dendritogenesis also provide
      a strong rationale for developing pharmacological means to manipulate ganglioside
      expression in neurons.

PMID- 12803924
TI  - Biochemistry of glycosphingolipid storage disorders: implications for therapeutic
      intervention.
AB  - The physiological importance of the degradative processes in lysosomes is
      revealed by the existence of at least 40 distinct inherited diseases, the so
      called lysosomal storage disorders. Most of these diseases are caused by a
      deficiency in a single lysosomal enzyme, or essential cofactor, and result in the
      lysosomal accumulation of one, or sometimes several, natural compounds. The most
      prevalent subgroup of the lysosomal storage disorders is formed by the
      sphingolipidoses, inherited disorders that are characterized by excessive
      accumulation of one or multiple (glyco)sphingolipids. The biology of
      glycosphingolipids has been extensively discussed in other contributions during
      this symposium. This review will therefore focus in depth on (type 1) Gaucher
      disease, a prototypical glycosphingolipidosis. The elucidation of the primary
      genetic defect, being a deficiency in the lysosomal glucocerebrosidase, is
      described. Characterization of glucocerebrosidase at protein and gene level has
      subsequently opened avenues for therapeutic intervention. The development of
      successful enzyme replacement therapy for type 1 Gaucher disease is discussed.
      Attention is also paid to the alternative approach of substrate modulation using
      orally administered inhibitors of glucosylceramide synthesis. Novel developments
      about the monitoring of age of onset, progression and correction of disease are
      described. The remaining challenges about pathophysiology of
      glycosphingolipidoses are discussed in view of further improvements in therapy
      for these debilitating disorders.

PMID- 12803925
TI  - Enzyme replacement therapy: conception, chaos and culmination.
AB  - Soon after the enzymatic defects in Gaucher disease and in Niemann-Pick disease
      were discovered, enzyme replacement or enzyme supplementation was proposed as
      specific treatment for patients with these and related metabolic storage
      disorders. While relatively straightforward in concept, successful implementation
      of this approach required many years of intensive effort to bring it to fruition.
      Procedures were eventually developed to produce sufficient quantities of the
      requisite enzymes for clinical trials and to target therapeutic enzymes to lipid
      storing cells. These achievements led to the development of effective enzyme
      replacement therapy for patients with Gaucher disease and for Fabry disease.
      These demonstrations provide strong incentive for the application of this
      strategy for the treatment of many human disorders of metabolism.

PMID- 12803926
TI  - Gene therapy: prospects for glycolipid storage diseases.
AB  - Lysosomal storage diseases comprise a group of about 40 disorders, which in most
      cases are due to the deficiency of a lysosomal enzyme. Since lysosomal enzymes
      are involved in the degradation of various compounds, the diseases can be further
      subdivided according to which pathway is affected. Thus, enzyme deficiencies in
      the degradation pathway of glycosaminoglycans cause mucopolysaccharidosis, and
      deficiencies affecting glycopeptides cause glycoproteinosis. In glycolipid
      storage diseases enzymes are deficient that are involved in the degradation of
      sphingolipids. Mouse models are available for most of these diseases, and some of
      these mouse models have been used to study the applicability of in vivo gene
      therapy. We review the rationale for gene therapy in lysosomal disorders and
      present data, in particular, about trials in an animal model of metachromatic
      leukodystrophy. The data of these trials are compared with those obtained with
      animal models of other lysosomal diseases.

PMID- 12803928
TI  - Substrate reduction therapy in mouse models of the glycosphingolipidoses.
AB  - Substrate reduction therapy uses small molecules to slow the rate of glycolipid
      biosynthesis. One of these drugs, N-butyldeoxynojirimycin (NB-DNJ), shows
      efficacy in mouse models of Tay-Sachs, Sandhoff and Fabry diseases. This offers
      the prospect that NB-DNJ may be of therapeutic benefit, at least in the juvenile
      and adult onset variants of these disorders. The infantile onset variants will
      require an additional enzyme-augmenting modality if the pathology is to be
      significantly improved. A second drug, N-butyldeoxyglactonojirimycin, looks very
      promising for treating storage diseases with neurological involvement as high
      systemic dosing is achievable without any side-effects.

PMID- 12803927
TI  - Small-molecule therapeutics for the treatment of glycolipid lysosomal storage
      disorders.
AB  - Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging
      group of human diseases to treat. Although these disorders appear to be monogenic
      in origin, where the catalytic activity of enzymes in GSL catabolism is impaired,
      the clinical presentation and severity of disease are heterogeneous. Present
      attitudes to treatment demand individual therapeutics designed to match the
      specific disease-related gene defect; this is an acceptable approach for those
      diseases with high frequency, but it lacks viability for extremely rare
      conditions. An alternative therapeutic approach termed 'substrate deprivation' or
      'substrate reduction therapy' (SRT) aims to balance cellular GSL biosynthesis
      with the impairment in catalytic activity seen in lysosomal storage disorders.
      The development of N-alkylated iminosugars that have inhibitory activity against
      the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic
      cells, ceramide-specific glucosyltransferase, offers a generic therapeutic for
      the treatment of all glucosphingolipidoses. The successful use of N-alkylated
      iminosugars to establish SRT as an alternative therapeutic strategy has been
      demonstrated in in vitro, in vivo and in clinical trials for type 1 Gaucher
      disease. The implications of these studies and the prospects of improvement to
      the design of iminosugar compounds for treating Gaucher and other GSL lysosomal
      storage disorders will be discussed.

PMID- 12803929
TI  - Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease.
AB  - Glycosphingolipid (GSL) lysosomal storage disorders are inherited enzyme
      deficiencies that result in pathological lysosomal accumulation of glycolipids,
      with widespread clinical consequences. Type 1 Gaucher disease is the commonest of
      these; the deficient enzyme in this condition is glucocerebrosidase. Clinical
      manifestations include hepatosplenomegaly, thrombocytopenia, anaemia, recurrent
      infections and skeletal lesions. The condition can be treated with intravenous
      enzyme replacement therapy (ERT). Substrate reduction therapy is a new approach
      in which glycolipid accumulation is counteracted not by replacing the deficient
      enzyme but by reducing the substrate level to better balance residual activity of
      the deficient enzyme. Miglustat is an inhibitor of glucosylceramide synthase, a
      key enzyme in GSL synthesis. Oral administration of miglustat to patients with
      type 1 Gaucher disease attenuates the synthesis of glucocerebroside, the
      substrate of the deficient glucocerebrosidase. In the first clinical study,
      patients with type 1 Gaucher disease who had enlargement of the liver or spleen
      and (if present) the spleen at baseline received 12 months treatment with oral
      miglustat. There were mean decreases in liver and spleen volumes of 12% (7.9
      16.4, p < 0.001) and 19% (14.3-23.7, p < 0.001), respectively. Mean haemoglobin
      increased by 0.26 g dl(-1) (-0.5-0.57, not statistically significant) and
      platelet count by 8.3 x 10(9) l(-1) (1.9-14.7, p = 0.014).

PMID- 12803930
TI  - Gaucher disease and the clinical experience with substrate reduction therapy.
AB  - Gaucher disease is caused by an enzymatic defect with consequent accumulation of
      glucocerebroside. Type I, the non-neuronopathic form, is rather common and
      panethnic. Patients may present with hepatosplenomegaly, anaemia,
      thrombocytopenia and skeletal or lung involvement. Enzyme replacement therapy
      ameliorates disease symptoms and signs; however, it involves lifelong intravenous
      therapy, is costly and is incapable of crossing the blood-brain barrier.
      Substrate reduction with N-butyldeoxynojirimycin (OGT 918) is a harbinger of oral
      iminosugars for glycolipid storage disorders. Long-term data in the seminal trial
      (100 mg three times per day), demonstrate safety and efficacy in adult type I
      patients naive to enzyme therapy, and suggest its application in patients
      unwilling or unable to receive enzyme replacement and tolerating side effects,
      including diarrhoea, weight loss, tremor and peripheral neuropathy (mostly
      reversible with dose reduction or withdrawal). Dose dependency was demonstrated
      with 50 mg three times per day. In patients stabilized on enzyme therapy switched
      from or in combination with enzyme, no deterioration in disease parameters was
      seen but side effects were as above. Although efficacy is less dramatic than
      enzyme treatment, it may be that plateaux are achieved asymptotically so
      therapeutic outcomes with OGT 918 may ultimately be comparable. Yet, given the
      above side effects and the lack of long-term experience, patients with very mild
      manifestations would probably not be appropriate candidates.

PMID- 12803931
TI  - Future perspectives for glycolipid research in medicine.
AB  - Medical interest in glycolipids has been mainly directed to the rare and complex
      glycosphingolipid storage disorders that are principally caused by unitary
      deficiencies of lysosomal acid hydrolases. However, glycolipids are critical
      components of cell membranes and occur within newly described membrane domains
      known as lipid rafts. Glycolipids are components of important antigen systems and
      membrane receptors; they participate in intracellular signalling mechanisms and
      may be presented to the immune system in the context of the novel CD1 molecules
      present on T lymphocytes. A knowledge of their mechanism of action in the control
      of cell growth and survival as well as developmental pathways is likely to shed
      light on the pathogenesis of the glycosphingolipid storage disorders as well as
      the role of lipid second messengers in controlling cell mobility and in the
      mobilization of intracellular calcium stores (a biological role widely postulated
      particularly for the lysosphingolipid metabolite sphingosine 1-phosphate). Other
      sphingolipid metabolites such as ceramide 1-phosphate may be involved in
      apoptotic responses and in phagocytosis and synaptic vesicle formation. The
      extraordinary pharmaceutical success of enzymatic complementation for Gaucher's
      disease using macrophage-targeted human glucocerebrosidase has focused further
      commercial interest in other glycolipid storage diseases: the cost of targeted
      enzyme therapy and its failure to restore lysosomal enzymatic deficiencies in the
      brain has also stimulated interest in the concept of substrate reduction therapy
      using diffusible inhibitory molecules. Successful clinical trials of the
      iminosugar N-butyldeoxynojirimycin in type 1 Gaucher's disease prove the
      principle of substrate reduction therapy and have attracted attention to this
      therapeutic method. They will also foster important further experiments into the
      use of glycolipid synthesis inhibitors for the severe neuronopathic
      glycosphingolipidoses, for which no definitive treatment is otherwise available.
      Future glycolipid research in medicine will be directed to experiments that shed
      light on the role of sphingolipids in signalling pathways, and in the
      comprehensive characterization and their secretory products in relation to the
      molecular pathogenesis of the storage disorders; experiments of use to improve
      the efficiency of complementing enzymatic delivery to the lysosomal compartment
      of storage cells are also needed. Further systematic screening for inhibitory
      compounds with specific actions in the pathways of glycosphingolipid biosynthesis
      will undoubtedly lead to clinical trials in the neuronopathic storage disorders
      and to wider applications in the fields of immunity and cancer biology.

PMID- 12803932
TI  - A historical perspective of the glycosphingolipids and sphingolipidoses.
AB  - Glycosphingolipids are a polysaccharide chain between 1 and 40 carbohydrate
      residues long glycosidically linked to ceramide (a long-chain aliphatic amino
      alcohol or sphingoid) that is embedded in the cell plasma membrane with the
      carbohydrate moiety on the outside. The sphingoid imparts rigidity to the
      membrane and the carbohydrate tails protect the cell surface and have functions
      in relation to cell adhesion, growth, regulation, differentiation, cell
      interaction, recognition and signalling. They provide adhesion sites for
      pathogens and change during oncogenic transformation. Ceramide is also a
      component of sphingomyelin. Glycosphingolipids are degraded by lysosomal
      hydrolysis. The sphingolipidoses are a series of diseases in which mutations
      affecting the enzymes catalysing the last 11 steps of this process causing
      abnormal compounds proximal to the metabolic block to accumulate
      intralysosomally. Thus, they are a sub-group of the lysosomal storage diseases.
      The degradation of sphingolipids containing three or less carbohydrate residues
      requires a sphingolipid activator protein and mutations affecting these proteins
      also cause abnormal glycosphingolipid storage. With one exception (Fabry disease,
      which is X linked) the sphingolipidoses are inherited autosomally. The phenotypic
      manifestations of the individual sphingolipidoses are variable although the more
      severe variants are usually the better known. They have generally been regarded
      as untreatable but notable therapeutic advances are being made by enzyme
      replacement therapy and regulating the rate of glycosphingolipid synthesis by
      inhibiting UDP-glucose-N-acylsphingosine D-glucosyl transferase (CerGlcT), which
      is the first reaction on the pathway of glycosphingolipid synthesis. The
      compounds used are N-alkylated iminosugars whose glucose and galactose
      stereochemistries inhibit CerGlcT. Prenatal and carrier state diagnosis, genetic
      counselling and the abortion of affected foetuses are reducing the incidence of
      some of the most severe sphingolipidoses in certain high-incidence populations.

PMID- 12803933
TI  - Exclusively young offenders: providing dedicated adolescent sexual clinics in
      English young offender institutions.

PMID- 12803936
TI  - Demand for sexual health services during the Olympic Games: both sides of the
      Sherman effect.
AB  - To determine the impact of the Olympic Games the Sydney Sexual Health Centre
      database was accessed for demographic, health care utilization, and morbidity
      variables for two periods of interest: 15-29 September 2000 (the 'Olympic
      period'), and 1-30 September 1999 ('1999 comparison period'). Differences were
      tested by chi-square statistics and by calculation of odds ratios (ORs) using
      SPSS. During the Olympic period twice as many of the new patients had arrived in
      Australia that year (35% c.f. 18%: OR 2.46, 95% CI 1.49-4.05, P=0.0002). Per
      attendance the proportion with symptoms or a known sexually transmitted infection
      (STI) contact was higher during the Games (29% c.f. 16% OR 1.67, 95% CI 1.1.27
      2.21, P=0.0002) and there was a marginally higher yield of bacterial STIs (6%
      c.f. 3%: OR 1.83, 95% CI 1.06-3.13 P=0.03). The normal clinic population was
      replaced by an increased proportion of symptomatic patients who were recent
      arrivals in Australia.

PMID- 12803935
TI  - Attitudes about human papillomavirus vaccine in young women.
AB  - Human papillomavirus (HPV) vaccines are under investigation, but little is known
      about attitudes regarding vaccination. The aims of this study were to identify
      attitudes about and intention to receive an HPV vaccine in young women using a
      theory-based model. Young women (n=52, mean age 25 years, range 18-30 years, 35%
      Black/Non-Hispanic) completed a survey assessing knowledge, attitudes about HPV
      vaccination, and risk behaviours. Associations between attitudes and intention to
      receive the vaccine were assessed using Mann-Whitney U or chi-square tests.
      Subjects reported positive attitudes about receiving an HPV vaccine and high
      intention to receive the vaccine both for themselves and their daughters.
      Variables associated significantly with intention included knowledge (P=0.004),
      personal beliefs about vaccination (P=0.004), belief that others would approve of
      vaccination (P=0.005), and higher number of sexual partners (P=0.028).
      Information on attitudes about HPV vaccination and predictors of intention to
      receive a vaccine may guide immunization initiatives for young adults.

PMID- 12803937
TI  - Anogenital warts contributing to the risk of squamous intraepithelial lesions
      among HIV-positive women of Sao Paulo, Brazil.
AB  - Unsafe sexual practices may expose HIV-positive women to high-grade squamous
      intraepithelial lesions (SIL) and to infection with oncogenic human
      papillomavirus (HPV) types. A cross sectional study of 141 HIV-positive women was
      designed to evaluate risk factors for the development of cervico-vaginal SIL and
      HPV-DNA detection/typing. Uni- and multivariate forward stepwise analysis was
      used to determine the relationship between risk variables and HPV infection and
      between risk behaviour, HPV and HIV infection with development of SIL. Univariate
      analysis showed that HPV-DNA infection was related to previous and recurrent
      anogenital warts, male genital warts and cytological alteration. For final
      multivariate analysis, both HPV type (undetermined- and high-risk, OR=29.3 and
      112.0, respectively) were statistically associated (P=0.019) with high-grade
      cervico-vaginal SIL. The presence of anogenital warts as well as high- and
      undetermined-risk HPV infection may alert to cyto/histopathological alterations.
      These results point out the importance of the use of barrier methods and routine
      early genitoscopy/treatment for HIV-infected partners.

PMID- 12803938
TI  - The management of penile intraepithelial neoplasia in genitourinary medicine.
AB  - The incidence of reporting of penile intraepithelial neoplasia (PIN) by
      genitourinary medicine clinics in the UK is rare. The reporting of higher
      incidence, in most international studies, is suggestive of under-diagnosis of PIN
      lesions in the UK, which leads to improper therapy and follow-up. A systematic
      literature review is undertaken, regarding the current state of management of PIN
      and the possible avenues of improvement in the diagnosis and follow-up. The role
      of genitourinary medicine clinics is examined, in view of the high number of
      patients that present with genital dermatological conditions, in whom there are
      patients with non-identified PIN lesions. The notable increase in reporting of
      vulval intraepithelial neoplasia has been associated with an increase in vulval
      cancer, especially in younger patients. The possibility of a similar trend in
      penile lesions needs to be observed and the association between high risk human
      papillomavirus (HPV) types, and genital intraepithelial neoplasia and cancer, is
      recognized and therefore an increased incidence in the diagnosis of HPV
      associated lesions must be considered.

PMID- 12803939
TI  - All STDs are not created equal: an analysis of the differential effects of sexual
      behaviour changes on different STDs.
AB  - The same sexual behaviours that transmit HIV are implicated in the transmission
      of certain other STDs, including chlamydia, gonorrhoea, and syphilis.
      Consequently, it is often assumed that preventive methods that are effective
      against HIV should be equally effective against other STDs. The purpose of this
      study was to examine this assumption. We applied a mathematical model of HIV/STD
      transmission to empirical data from a large HIV prevention intervention that
      stressed sexual behaviour change. We modelled the effects of two behavioural
      strategies - reducing the number of sex partners and increasing condom use-on the
      proportionate change in intervention participants' cumulative risk of acquiring
      HIV or a highly-infectious STD, such as gonorrhoea. The results of this modelling
      exercise indicate that decreasing the number of partners is a more effective
      strategy for reducing STD risk than it is for HIV risk. In contrast, condoms are
      somewhat more effective at reducing the cumulative transmission risk for HIV than
      for highly infectious STDs. The protection provided by condoms for multiple acts
      of intercourse critically depends on the infectiousness of the STD. The results
      of this study suggest caution in extrapolating from one STD to another, or from
      one behavioural risk reduction strategy to another.

PMID- 12803940
TI  - Routine questioning about non-consenting sex: a survey of practice in
      Australasian sexual health clinics.
AB  - The objectives of the study were, 1. To ascertain if sexual health physicians and
      practitioners believe a question concerning a past history of non-consensual sex
      should be asked routinely and are asking it. 2. To identify whether sexual health
      services have established protocols to integrate this question into practice. 3.
      To identify the barriers to this becoming part of a routine sexual health
      history. A questionnaire covering demographics, protocols and practice around
      asking the question and reasons for not asking was sent to all (20) sexual health
      clinics in New Zealand and 7 sexual health clinics in Australia, inviting
      participation from all staff who took routine sexual health histories. Twenty
      seven sexual health clinics participated with a total of 122 (69% response rate)
      questionnaires completed and returned. One hundred and thirteen (93%)
      participants believed it was a relevant question to ask. Seventy-eight (63%) said
      asking the question was encouraged, and routinely or mostly asked the question.
      Only 40 (33%) identified their workplace had a written policy and 52 (43%) had
      not received specific training in asking the question. The majority who asked
      routinely said their client never or rarely objected and that it did not often
      add significantly to the time. The main reasons for not asking were the belief it
      was nothing to do with the person's presenting complaint, concern the client
      would find it too disturbing, inadequate training, and lack of time. Sexual
      health clinics should develop protocols and guidelines and provide appropriate
      training to ensure that routine questioning about non-consenting sex is
      integrated into safe practice.

PMID- 12803941
TI  - Street outreach for HIV prevention: effectiveness of a state-wide programme.
AB  - Street outreach is considered a key HIV prevention strategy in the United States.
      To determine whether street outreach to prevent HIV infection as practised by
      state-funded community-based organizations (CBOs) is effective in promoting
      condom use, we conducted an evaluation using a quasi-experimental design. Twenty
      one CBOs involved in street outreach conducted cross-sectional surveys assessing
      risk behaviour and exposure to outreach activities in 66 intervention and 13
      comparison areas in Louisiana over a 2-year period. Surveys were collected from
      4950 persons at intervention sites and 1597 persons at comparison sites. After
      controlling for demographic characteristics and sexual risk factors, persons in
      intervention sites were more likely to use condoms than persons in comparison
      sites [odds ratio 1.37 (95% confidence interval 1.20, 1.56; P<0.001)]. Contact
      with an outreach worker mediated condom use. The mechanism of effect may be
      related to direct contact with an outreach worker and condom distribution rather
      than to broader community mobilization.

PMID- 12803942
TI  - Previous STI and risk of HIV infection in men.
AB  - To determine the prevalence of a previous history of sexually transmitted
      infection (STI) and its influence as a risk factor for HIV infection among men
      tested for HIV, data from men having a voluntary HIV test at the STI Unit of
      Barcelona during a 6-month period of 1998 were analysed. Descriptive and logistic
      regression analysis were done to examine the prevalence of previous STI and
      factors associated with HIV infection. Prevalences of HIV were 5.6% in
      homo/bisexual and 0.5% in heterosexual men (P<0.001). Risk factors for HIV were
      STI history: odds ratio (OR)=8.7 and homo/bisexual behaviour: OR=6.6; 19.8% of
      heterosexuals had a history of STI compared with 44.2% of homo/bisexual men
      (P<0.01). A previous STI was associated with HIV seropositivity in homosexual
      men.

PMID- 12803943
TI  - Sexual behaviour and social class in Australian women.
AB  - Sexual behaviour is determined by social, cultural and personal factors. Sexual
      behaviour studies have been conducted in many countries. However, information
      from Australia is limited. This study was conducted in Obstetrics Department,
      Westmead Hospital, Sydney. Questionnaire-derived demographic and behavioural
      characteristics for public and private patients were compared using bivariate and
      logistic regression analyses. Of the patients, 3036 were public, and 595 private.
      On bivariate analysis some significant differences were private patients more
      likely to be born in Australia and have a higher education level whereas public
      patients were more likely to have had a greater number of lifetime sexual
      partners and younger age at first sex. Public patients were more likely to be
      herpes simplex virus type 2 (HSV-2) antibody positive (12%) than private patients
      (6%). On logistic regression significant variables included country of birth,
      being HSV-2 antibody positive, and age at first sex. A number of sexual and
      social variables were significantly different, comparing patients in the public
      and private sectors. Evaluation of interventions to reduce the sexual risk to
      women in the public sector should be considered, including encouraging young
      women to delay their sexual debut, and reducing the number of sexual partners.

PMID- 12803945
TI  - Systemic and discoid lupus erythematosus in HIV-infected patients treated with
      highly active antiretroviral therapy.
AB  - Although HIV infection is often associated with several rheumatic diseases, the
      coexistence of this retroviral infection and systemic lupus erythematosus (SLE)
      is extremely uncommon. Generally, HIV-related immunosuppression improves SLE
      symptoms, and antiretroviral therapy may lead to an autoimmune disease flare
      subsequent to the increase of circulating CD4+ cell number. Two HIV-infected
      female patients with SLE and discoid lupus erythematosus (DLE) diagnosed a few
      months after the highly active antiretroviral therapy initiation, are described.
      To our knowledge, this is the second case of DLE and the twenty-seventh case of
      SLE reported to date in association with HIV infection.

PMID- 12803944
TI  - Hydroxyurea in combination with didanosine and stavudine in antiretroviral
      experienced HIV-infected subjects with a review of the literature.
AB  - The safety and efficacy of hydroxyurea with didanosine in combination with
      stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced
      patients was investigated. Entry criteria included HIV-1 infected, NRTI
      experienced adults, with CD4(+) counts 50-550 cells/mm(3) and viral loads
      >or=12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day
      (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty
      one HIV-1 subjects with mean bDNA viral load 1x10(5) log(10) copies/mL and mean
      CD4(+) T-cell counts of 231 cells/mm(3) were enrolled. A 1.3 log(10) decrease in
      mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in
      a more rapid response to therapy compared with prior zidovudine use. Side effects
      consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in
      four subjects and resolved upon withdrawal of therapy. This non-randomized study
      in subjects with a mean CD4(+) T-cell count of 230 cells/mm(3) demonstrates the
      antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to
      therapy need to be followed closely. The results support the need for a
      randomized, prospective study to determine the safety and efficacy of hydroxyurea
      plus didanosine in antiretroviral-experienced patients with CD4(+) cell counts
      below 300 cells/mm(3).

PMID- 12803946
TI  - Screening for non-gonococcal urethritis.

PMID- 12803947
TI  - The funding and organization of infection control in NHS hospital trusts: a study
      of infection control professionals' views.
AB  - The problems associated with hospital-acquired infection have been causing
      increasing concern in England in recent years. This paper reports the results of
      a nationwide survey of hospital infection control professionals' views concerning
      the organizational structures used to manage and obtain funding for control of
      infection. A complex picture with significant variation between hospitals
      emerges. Although government policy dictates that specific funding for hospital
      infection control is formally made available, it is not always the case that
      infection control professionals have adequate resources to undertake their roles.
      In some cases this reflects the failure of hospitals' infection control budgetary
      mechanisms; in others it reflects the effects of decentralizing budgets to
      directorate or ward level. Some use was made of informal mechanisms either to
      supplement or to substitute for the formal ones. But almost all infection control
      professionals still believed they were constrained in their ability to protect
      the hospital population from the risk of infectious disease. It is clear that
      recent government announcements that increased effort will be made to support
      local structures and thereby improve the control of hospital acquired infection
      are to be welcomed.

PMID- 12803948
TI  - Perceived access in a managed care environment: determinants of satisfaction.
AB  - With increasing competition in the local and regional healthcare markets, and
      growing interest in assessing the effectiveness of services and patient outcomes,
      satisfaction measures are becoming prominent in evaluating the performance of the
      healthcare system. This study examines the independent effect of predisposing,
      enabling and medical need factors on perceived access to care with particular
      focus on insurance plans. A survey questionnaire is developed to investigate
      access limitations at three levels: (1) the health plan, (2) the individual
      provider(s) and (3) the healthcare organization. In addition, shortage of
      providers, residents' perceptions of their health status, satisfaction with
      access to care and socio-demographic indicators are incorporated into the
      analysis. Multivariate logistic regression is used to assess the independent
      effects of the above factors on a dichotomous dependent variable--residents'
      overall satisfaction with access to healthcare services. The most salient
      determinants of overall satisfaction with access to care were the type of health
      insurance plan, cost of insurance premiums, co-payments, difficulty with
      obtaining referrals, self-rated general health, the opportunity cost of taking
      time to see a provider (measured by the loss of hourly wages), marital status and
      the age factor over 80 years.

PMID- 12803949
TI  - Tools of the trade: a comparative analysis of approaches to priority setting in
      healthcare.
AB  - In many countries, local managers and clinicians have been given responsibility
      to set health priorities and allocate resources accordingly. Although tools have
      been suggested for use in aiding this process, knowledge of these tools within
      health regions is lacking and comparative analysis in the literature is limited.
      Several approaches to priority setting are critiqued from both practical and
      theoretical perspectives, and a tangible way forward for such activity is
      provided. The approaches analysed include: needs assessment, core services,
      economic evaluation including quality-adjusted life year league tables, and
      programme budgeting and marginal analysis (PBMA). Needs assessment fails to
      recognize underlying economic principles of opportunity cost and the margin,
      while core services ignores the margin and has had limited impact in practice.
      Economic evaluations can consider marginal costs and benefits, but cannot always
      be used to inform decisions in a timely manner. PBMA is based on underlying
      economic principles and can pragmatically respond to objectives related to both
      efficiency and equity. Although PBMA is not without challenges, from an economic
      perspective, it does seem to "get the thinking right", and, importantly, as a
      process, can incorporate some of the other approaches to priority setting
      discussed in this paper.

PMID- 12803950
TI  - Barriers to evidence-based decision making among Polish healthcare managers.
AB  - The 1999 reform of the Polish healthcare system revealed deficiencies in the
      research base and a lack of organized systems of information provision.
      Professionals who most need effective information systems are policymakers and
      healthcare managers. The main aim of the described study was to obtain data
      describing the needs, preferences and limitations of healthcare managers as
      information users, and to identify environmental factors influencing their
      information behaviour. A national postal survey was conducted and supplemented
      with information collected during focus groups, semi-structured interviews and
      through analysis of relevant policy documents. The target population included
      hospital chief executives, medical directors, head nurses and directors of the
      institutions responsible for health services planning and purchasing. Target
      institutions were drawn systematically from official lists, stratified by regions
      of the country and hospital reference level. The interviews were conducted with
      primary care unit managers and with Ministry of Health officials. National health
      strategy and directives, cost-effectiveness analyses of interventions and
      clinical practice guidelines emerged as information of primary importance to
      respondents. The main barriers to effective information behaviour were found to
      be: attitudes towards research activity, lack of appropriately processed data,
      lack of skills enabling information seeking and appraisal, inappropriate format
      of publications, ineffective dissemination of information and absence of services
      facilitating access to evidence. The current information environment of
      healthcare managers, together with their attitude towards information and
      deficiencies in information skills, appear to serve as a barrier to evidence
      based practice in the Polish healthcare system.

PMID- 12803951
TI  - Why is high-tech healthcare at home purchasing underdeveloped and what could be
      done to improve it?
AB  - Executive Letter (95)5 initiated a change of health policy preventing general
      practitioners (GPs) from prescribing packages of "high-tech healthcare at home"
      (HTHC). From 1 April 1995, district health authorities were required to establish
      contracts to purchase such care. Several reasons were behind this policy change
      including the belief that contracting would improve service quality by
      encouraging competition between potential suppliers, securing better value for
      money, and establishing service specifications and monitoring mechanisms. Our
      survey of 98 health authorities, however, highlighted that contracting for home
      total parenteral nutrition, intravenous antibiotics for patients with cystic
      fibrosis, intravenous chemotherapy and continuous ambulatory peritoneal dialysis
      is largely undeveloped. The majority of districts contracted with historic
      providers and authorities freely admitted that they did not know whether they
      were obtaining value for money or a service of adequate quality. Only three
      districts had developed a strategy for purchasing HTHC as required by the
      Executive Letter, and only 17 had plans to re-examine their approach. Contracting
      for HTHC presents practical problems, including the complexity of the process and
      the significant time demands for efficient and effective contracting. Phase two
      of this research sought to produce a "guide to good practice" for health
      authorities wishing to re-examine and improve their purchasing. We conducted case
      study analyses in districts that had made effective progress and those that had
      encountered difficulties, drawing upon lessons learned. We reported our findings
      to the NHS Executive and supplemented this with a "toolbox" that included sample
      documents covering areas such as tendering, monitoring mechanisms, service
      specifications and different purchasing approaches.

PMID- 12803952
TI  - Accessibility of selected hospitals and medical procedures by means of aerial and
      transit network-based measures.
AB  - OBJECTIVE: This report investigates the use of linear and travelled route
      (transit network-based) distances in estimating the accessibility of hospitals to
      patients, for some selected hospital admission diagnostics. METHODS: For patients
      admitted to 14 public hospitals in Rio de Janeiro City, during 1996, under the
      ICD-9 headings "Complications of Pregnancy, Childbirth and the Puerperium" and
      "Disorders of the Circulatory System", average distances between the patient's
      district of residence and hospital of admission were calculated (both as
      Euclidean and as network-based distances). Data were obtained from the country's
      public health data processing agency. Geographic co-ordinates were obtained for
      districts of residence from the postal codes of the patients' residences.
      Distances were estimated with the TransCAD Geographical Information System, based
      on a map of the city transit network. There were 8654 patients admitted under the
      "Complications of Pregnancy" heading and 3439 under "Disorders of Circulatory
      System". RESULTS: Variations of up to a factor of 5.3, and up to 34 km, could be
      identified between linear and network estimates. CONCLUSION: While recognizing
      that network estimates have advantages, the literature on accessibility
      frequently argues that aerial estimates are a good approximation for those. The
      present results show that this is not necessarily the case.

PMID- 12803953
TI  - Estimating a state-space model from point process observations.
AB  - A widely used signal processing paradigm is the state-space model. The state
      space model is defined by two equations: an observation equation that describes
      how the hidden state or latent process is observed and a state equation that
      defines the evolution of the process through time. Inspired by neurophysiology
      experiments in which neural spiking activity is induced by an implicit (latent)
      stimulus, we develop an algorithm to estimate a state-space model observed
      through point process measurements. We represent the latent process modulating
      the neural spiking activity as a gaussian autoregressive model driven by an
      external stimulus. Given the latent process, neural spiking activity is
      characterized as a general point process defined by its conditional intensity
      function. We develop an approximate expectation-maximization (EM) algorithm to
      estimate the unobservable state-space process, its parameters, and the parameters
      of the point process. The EM algorithm combines a point process recursive
      nonlinear filter algorithm, the fixed interval smoothing algorithm, and the state
      space covariance algorithm to compute the complete data log likelihood
      efficiently. We use a Kolmogorov-Smirnov test based on the time-rescaling theorem
      to evaluate agreement between the model and point process data. We illustrate the
      model with two simulated data examples: an ensemble of Poisson neurons driven by
      a common stimulus and a single neuron whose conditional intensity function is
      approximated as a local Bernoulli process.

PMID- 12803954
TI  - Sequential Bayesian decoding with a population of neurons.
AB  - Population coding is a simplified model of distributed information processing in
      the brain. This study investigates the performance and implementation of a
      sequential Bayesian decoding (SBD) paradigm in the framework of population
      coding. In the first step of decoding, when no prior knowledge is available,
      maximum likelihood inference is used; the result forms the prior knowledge of
      stimulus for the second step of decoding. Estimates are propagated sequentially
      to apply maximum a posteriori (MAP) decoding in which prior knowledge for any
      step is taken from estimates from the previous step. Not only do we analyze the
      performance of SBD, obtaining the optimal form of prior knowledge that achieves
      the best estimation result, but we also investigate its possible biological
      realization, in the sense that all operations are performed by the dynamics of a
      recurrent network. In order to achieve MAP, a crucial point is to identify a
      mechanism that propagates prior knowledge. We find that this could be achieved by
      short-term adaptation of network weights according to the Hebbian learning rule.
      Simulation results on both constant and time-varying stimulus support the
      analysis.

PMID- 12803956
TI  - Gamma rhythmic bursts: coherence control in networks of cortical pyramidal
      neurons.
AB  - Much evidence indicates that synchronized gamma-frequency (20-70 Hz) oscillation
      plays a significant functional role in the neocortex and hippocampus. Chattering
      neuron is a possible neocortical pacemaker for the gamma oscillation. Based on
      our recent model of chattering neurons, here we study how gamma-frequency
      bursting is synchronized in a network of these neurons. Using a phase oscillator
      description, we first examine how two coupled chattering neurons are
      synchronized. The analysis reveals that an incremental change of the bursting
      mode, such as from singlet to doublet, always accompanies a rapid transition from
      antisynchronous to synchronous firing. The state transition occurs regardless of
      what changes the bursting mode. Within each bursting mode, the neuronal activity
      undergoes a gradual change from synchrony to antisynchrony. Since the sensitivity
      to Ca(2+) and the maximum conductance of Ca(2+)-dependent cationic current as
      well as the intensity of input current systematically control the bursting mode,
      these quantities may be crucial for the regulation of the coherence of local
      cortical activity. Numerical simulations demonstrate that the modulations of the
      calcium sensitivity and the amplitude of the cationic current can induce rapid
      transitions between synchrony and asynchrony in a large-scale network of
      chattering neurons. The rapid synchronization of chattering neurons is shown to
      synchronize the activities of regular spiking pyramidal neurons at the gamma
      frequencies, as may be necessary for selective attention or binding processing in
      object recognition.

PMID- 12803957
TI  - Manhattan world: orientation and outlier detection by Bayesian inference.
AB  - This letter argues that many visual scenes are based on a "Manhattan" three
      dimensional grid that imposes regularities on the image statistics. We construct
      a Bayesian model that implements this assumption and estimates the viewer
      orientation relative to the Manhattan grid. For many images, these estimates are
      good approximations to the viewer orientation (as estimated manually by the
      authors). These estimates also make it easy to detect outlier structures that are
      unaligned to the grid. To determine the applicability of the Manhattan world
      model, we implement a null hypothesis model that assumes that the image
      statistics are independent of any three-dimensional scene structure. We then use
      the log-likelihood ratio test to determine whether an image satisfies the
      Manhattan world assumption. Our results show that if an image is estimated to be
      Manhattan, then the Bayesian model's estimates of viewer direction are almost
      always accurate (according to our manual estimates), and vice versa.

PMID- 12803960
TI  - The time-organized map algorithm: extending the self-organizing map to
      spatiotemporal signals.
AB  - The new time-organized map (TOM) is presented for a better understanding of the
      self-organization and geometric structure of cortical signal representations. The
      algorithm extends the common self-organizing map (SOM) from the processing of
      purely spatial signals to the processing of spatiotemporal signals. The main
      additional idea of the TOM compared with the SOM is the functionally reasonable
      transfer of temporal signal distances into spatial signal distances in
      topographic neural representations. This is achieved by neural dynamics of
      propagating waves, allowing current and former signals to interact
      spatiotemporally in the neural network. Within a biologically plausible
      framework, the TOM algorithm (1) reveals how dynamic neural networks can self
      organize to embed spatial signals in temporal context in order to realize
      functional meaningful invariances, (2) predicts time-organized representational
      structures in cortical areas representing signals with systematic temporal
      relation, and (3) suggests that the strength with which signals interact in the
      cortex determines the type of signal topology realized in topographic maps (e.g.,
      spatially or temporally defined signal topology). Moreover, the TOM algorithm
      supports the explanation of topographic reorganizations based on time-to-space
      transformations (Wiemer, Spengler, Joublin, Stagge, & Wacquant, 2000).

PMID- 12803961
TI  - New conditions on global stability of Cohen-Grossberg neural networks.
AB  - In this letter, we discuss the dynamics of the Cohen-Grossberg neural networks.
      We provide a new and relaxed set of sufficient conditions for the Cohen-Grossberg
      networks to be absolutely stable and exponentially stable globally. We also
      provide an estimate of the rate of convergence.

PMID- 12803963
TI  - Feedback in hypothesis testing: an ERP study.
AB  - We used event-related potentials (ERPs) to probe the effects of feedback in a
      hypothesis testing (HT) paradigm. Thirteen college students serially tested
      hypotheses concerning a hidden rule by judging its presence or absence in
      triplets of digits and revised them on the basis of an exogenous performance
      feedback. ERPs time-locked to performance feedback were then examined. The
      results showed differences between responses to positive and negative feedback at
      all cortical sites. Negative feedback, indicating incorrect performance, was
      associated to a negative deflection preceding a P300-like wave. Spatiotemporal
      principal component analysis (PCA) showed the interplay between early frontal
      components and later central and posterior ones. Lateralization of activity was
      selectively detectable at frontal sites, with a left frontal dominance for both
      positive and negative feedback. These results are discussed in terms of a
      proposed computational model of trial-to-trial feedback in HT in which the
      cognitive and emotive aspects of feedback are explicitly linked to putative
      mediating brain mechanisms. The properties of different feedback types and
      feedback-related deficits in depression are also discussed.

PMID- 12803962
TI  - Representation of change: separate electrophysiological markers of attention,
      awareness, and implicit processing.
AB  - Awareness of change within a visual scene only occurs in the presence of focused
      attention. When two versions of a complex scene are presented in alternating
      sequence separated by a blank mask, unattended changes usually remain undetected,
      although they may be represented implicitly. To test whether awareness of change
      and focused attention had the same or separable neurophysiological substrates,
      and to search for the neural substrates of implicit representation of change, we
      recorded event-related brain potentials (ERPs) during a change blindness task.
      Relative to active search, focusing attention in the absence of a change enhanced
      an ERP component over frontal sites around 100-300 msec after stimulus onset, and
      in posterior sites at the 150-300 msec window. Focusing attention to the location
      of a change that subjects were aware of, replicated those attentional effects,
      but also produced a unique positive deflection in the 350-600 msec window,
      broadly distributed with its epicenter in mediocentral areas. The unique
      topography and time course of this latter modulation, together with its
      dependence on the aware perception of change, distinguishes this "awareness of
      change" electrophysiological response from the electrophysiological effects of
      focused attention. Finally, implicit representation of change elicited a distinct
      electrophysiological event: Unaware changes triggered a positive deflection at
      the 240-300 msec window, relative to trials with no change. Overall, the present
      data suggest that attention, awareness of change, and implicit representation of
      change may be mediated by separate underlying systems.

PMID- 12803964
TI  - Temporal modulation of spatial tactile extinction in right-brain-damaged
      patients.
AB  - Unilateral and bilateral electrotactile stimuli were delivered to both hands of
      11 right-brain-damaged (RBD) patients with left tactile extinction and 20 healthy
      subjects. Bimanual stimuli could be presented simultaneously or with varying
      stimulus onset asynchronies (SOAs). Subjects indicated their detection of
      unilateral or bilateral stimuli, their judgements of whether stimuli were
      simultaneous or successive, and, in the latter case, which side came first. In
      RBD patients, extinction was maximal with simultaneous presentations and
      decreased as SOA increased. With short SOAs, omissions of left-sided stimuli
      occurred with both right-side and left-side stimulus precedence, suggesting a
      forward and backward interference of the right stimulus on the processing of the
      left stimulus within a time window of at least 100 msec. In contrast, there was
      no interference of the left stimulus on the detection of the right stimulus.
      Unlike controls, extinction patients rarely expressed simultaneity judgements,
      but those that were produced tended to be veridical or nearly so, like in normal
      controls. Whereas controls expressed generally accurate judgements of right or
      left precedence, patients showed a bias toward a right precedence and a maximal
      uncertainty between left-first and right-first choices when the left stimulus had
      a lead between 100 and 200 msec. The results are consistent with the hypothesis
      that, as in other sensory modalities, tactile extinction is associated with an
      abnormal persistent bias of attention toward the ipsilesional side that delays
      the processing of contralesional stimuli. However, the finding that both
      extinction and explicit judgements of simultaneity tended to occur with
      simultaneous bilateral stimuli suggest the presence of some residual neural
      capacity to detect precise temporal coincidence.

PMID- 12803965
TI  - Effects of form familiarity on perception of words, pseudowords, and nonwords in
      the two cerebral hemispheres.
AB  - Previous investigations of hemispheric processes of word perception provide a
      mixed picture of the sensitivity of each hemisphere to the familiarity of the
      visual form of lateralized displays. We investigated this issue by presenting
      words, pseudowords, and nonwords briefly to either the left (LH) or right (RH)
      hemisphere in lowercase, uppercase, and a matched, unfamiliar mixed-case form,
      and used an eye tracker to ensure central fixation and the Reicher-Wheeler task
      to suppress influences of stimulus asymmetry. Familiarity of form exerted a
      substantial effect on perception. In particular, perception of LH and RH displays
      of words, pseudowords, and nonwords was least accurate for mixed case,
      intermediate for upper case, and most accurate for lowercase. However, form had
      no effect on the LH advantage observed for words, pseudowords, and nonwords,
      indicating that form affected processing in both hemispheres to a similar extent.
      Moreover, LH and RH displays both showed that mixed case disrupted performance
      most for words, and more for pseudowords than for nonwords, indicating the
      sensitivity to form shown by each hemisphere reflected more than a general
      perceptual process. Implications for the role of form familiarity in hemispheric
      processing of words are discussed.

PMID- 12803966
TI  - Short-term reorganization of auditory analysis induced by phonetic experience.
AB  - Sine wave replicas of spoken words can be perceived both as nonphonetic auditory
      forms and as words, depending on a listener's experience. In this study, brain
      areas activated by sine wave words were studied with fMRI in two conditions: when
      subjects perceived the sounds spontaneously as nonphonetic auditory forms ("nive
      condition") and after instruction and brief practice attending to their phonetic
      attributes ("informed condition"). The test items were composed such that half
      replicated natural words ("phonetic items") and the other half did not, because
      the tone analogs of the first and third formants had been temporally reversed
      ("nonphonetic items"). Subjects were asked to decide whether an isolated tone
      analog of the second formant (T2) presented before the sine wave word (T1234) was
      included in it. Experience in attending to the phonetic properties of the
      sinusoids interfered with this auditory matching task and was accompanied by a
      decrease in auditory cortex activation with word replicas but not with the
      acoustically matched nonphonetic items. Because the activation patterns elicited
      by equivalent acoustic test items depended on a listener's awareness of their
      phonetic potential, this indicates that the analysis of speech sounds in the
      auditory cortex is distinct from the simple resolution of auditory form, and is
      not a mere consequence of acoustic complexity. Because arbitrary acoustic
      patterns did not evoke the response observed for phonetic patterns, these
      findings suggest that the perception of speech is contingent on the presence of
      familiar patterns of spectral variation. The results are consistent with a short
      term functional reorganization of auditory analysis induced by phonetic
      experience with sine wave replicas and contingent on the dynamic acoustic
      structure of speech.

PMID- 12803967
TI  - Reasoning, models, and images: behavioral measures and cortical activity.
AB  - The goal of this study was to investigate the neurocognitive processes of mental
      imagery in deductive reasoning. Behavioral studies yielded four sorts of verbal
      relations: (1) visuospatial relations that are easy to envisage both visually and
      spatially; (2) visual relations that are easy to envisage visually but hard to
      envisage spatially; (3) spatial relations that are hard to envisage visually but
      easy to envisage spatially; and (4) control relations that are hard to envisage
      both visually and spatially. In three experiments, visual relations slowed the
      process of reasoning in comparison with control relations, whereas visuospatial
      and spatial relations yielded inferences comparable to those of control
      relations. An experiment using functional magnetic resonance imaging showed that
      in the absence of any correlated visual input (problems were presented
      acoustically via headphones), all types of reasoning problems evoked activity in
      the left middle temporal gyrus, in the right superior parietal cortex, and
      bilaterally in the precuneus. In the prefrontal cortex, increased activity was
      found in the middle and inferior frontal gyri. However, only the problems based
      on visual relations also activated areas of the visual association cortex
      corresponding to V2. The results indicate that cortical activity during reasoning
      depends on the nature of verbal relations. All relations elicit mental models
      that underlie reasoning, but visual relations in addition elicit visual images.
      This account resolves inconsistencies in the previous literature.

PMID- 12803968
TI  - Dissociating explicit and implicit category knowledge with fMRI.
AB  - Neuroimaging of healthy volunteers identified separate neural systems supporting
      the expression of category knowledge depending on whether the learning mode was
      intentional or incidental. The same visual category was learned either
      intentionally or implicitly by two separate groupsof participants. During a
      categorization test, functional magnetic resonance imaging (fMRI) was used to
      compare brain activity evoked by category members and nonmembers. After implicit
      learning, when participants had learned the category incidentally, decreased
      occipital activity was observed for novel categorical stimuli compared with
      noncategorical stimuli. In contrast, after intentional learning, novel
      categorical stimuli evoked increased activity in the hippocampus, right
      prefrontal cortex, left inferior temporal cortex, precuneus, and posterior
      cingulate. Even though the categorization test was identical in the two
      conditions, the differences in brain activity indicate differing representations
      of category knowledge depending on whether the category had been learned
      intentionally or implicitly.

PMID- 12803969
TI  - Human cerebellum: surface-assisted cortical parcellation and volumetry with
      magnetic resonance imaging.
AB  - We describe a system of surface-assisted parcellation (SAP) of the human
      cerebellar cortex derived from neural systems functional and behavioral anatomy.
      This system is based on MRI and preserves the unique morphologic and topographic
      features of the individual cerebellum. All major fissures of the cerebellum were
      identified and traced in the flattened representation of the cerebellar cortex
      using the program "FreeSurfer." Parcellation of the cerebellar cortex followed
      using the fissure information in conjunction with landmarks using the program
      "Cardviews" to create 64 gyral-based cerebellar parcellation units. Computer
      assisted algorithms enable the execution of the cerebellar parcellation procedure
      as well as volumetric measurements and topographic localization. The SAP
      technique makes it possible to represent multimodal structural and functional
      imaging data on the flattened surface of the cerebellar cortex as illustrated in
      one functional MRI experiment.

PMID- 12803970
TI  - A cortical mechanism for triggering top-down facilitation in visual object
      recognition.
AB  - The majority of the research related to visual recognition has so far focused on
      bottom-up analysis, where the input is processed in a cascade of cortical regions
      that analyze increasingly complex information. Gradually more studies emphasize
      the role of top-down facilitation in cortical analysis, but it remains something
      of a mystery how such processing would be initiated. After all, top-down
      facilitation implies that high-level information is activated earlier than some
      relevant lower-level information. Building on previous studies, I propose a
      specific mechanism for the activation of top-down facilitation during visual
      object recognition. The gist of this hypothesis is that a partially analyzed
      version of the input image (i.e., a blurred image) is projected rapidly from
      early visual areas directly to the prefrontal cortex (PFC). This coarse
      representation activates in the PFC expectations about the most likely
      interpretations of the input image, which are then back-projected as an "initial
      guess" to the temporal cortex to be integrated with the bottom-up analysis. The
      top-down process facilitates recognition by substantially limiting the number of
      object representations that need to be considered. Furthermore, such a rapid
      mechanism may provide critical information when a quick response is necessary.

PMID- 12803971
TI  - Subcortical loop activation during selection of currently relevant memories.
AB  - Clinical studies on spontaneous confabulation and imaging studies with healthy
      subjects indicate that the anterior limbic system, in particular, the
      orbitofrontal cortex (OFC), is necessary to adjust thought and behavior to
      current reality. It appears to achieve this by continuously suppressing activated
      memories that do not pertain to ongoing reality, even before their content is
      consciously recognized. In the present study, we explored through what anatomical
      connections the OFC exerts this influence. Healthy subjects were scanned with
      H(2)(15)O PET as they performed four blocks of continuous recognition tasks, each
      block composed of a different type of stimuli (meaningful designs, geometric
      designs, words, nonwords). Within each block, three runs composed of exactly the
      same picture series, arranged in different order each time, were made. Subjects
      were asked to indicate item recurrences only within the currently ongoing run and
      to disregard familiarity from previous runs. In the combined first runs, in which
      all items were initially new and responses could be based on familiarity
      judgement (with repeated items) alone, we found medial temporal and right
      orbitofrontal activation. In the combined third runs, when all items were already
      known and selection of currently relevant memories was required, we found left
      orbitofrontal activation contingent with distinct activation of the ventral
      striatum, head and body of the caudate nucleus, substantia nigra, and medial
      thalamus. The study indicates that the OFC influences the cortical representation
      of memories through subcortical connections including the basal ganglia and the
      thalamus. The data are compatible with a role of the dopaminergic reward system
      in the monitoring of ongoing reality in thinking.

PMID- 12803972
TI  - Facilitation of implicit motor learning by weak transcranial direct current
      stimulation of the primary motor cortex in the human.
AB  - Transcranially applied weak direct currents are capable of modulating motor
      cortical excitability in the human. Anodal stimulation enhances excitability,
      cathodal stimulation diminishes it. Cortical excitability changes accompany motor
      learning. Here we show that weak direct currents are capable of improving
      implicit motor learning in the human. During performance of a serial reaction
      time task, the primary motor cortex, premotor, or prefrontal cortices were
      stimulated contralaterally to the performing hand. Anodal stimulation of the
      primary motor cortex resulted in increased performance, whereas stimulation of
      the remaining cortices had no effect. We conclude that the primary motor cortex
      is involved in the acquisition and early consolidation phase of implicit motor
      learning.

PMID- 12803973
TI  - Application of proteomics technology to the field of neurotrauma.
AB  - Near-completion of the Human Genome Project has stimulated scientists to begin
      looking for the next step in unraveling normal and abnormal functions within
      biological systems. Consequently, there is new focus on the role of proteins in
      these processes. Proteomics is a burgeoning field that may provide a valuable
      approach to evaluate the post-traumatic central nervous system (CNS). Although we
      cannot provide a comprehensive assessment of all methods for protein analysis,
      this report summarizes some of the newer proteomic technologies that have
      propelled this field into the limelight and that are available to most
      researchers in neurotrauma. Three technical approaches (two-dimensional gel
      electrophoresis, direct analysis by mass spectrometry, including two-dimensional
      chromatography coupled to mass spectrometry and isotope coded affinity tags, and
      antibody technologies) are reviewed, and their advantages and disadvantages
      presented. A discussion of proteomic technology in the context of brain and
      spinal cord trauma follows, addressing current and future challenges. Proteomics
      will likely be very useful for developing diagnostic predictors after CNS injury
      and for mapping changes in proteins after injury in order to identify new
      therapeutic targets. Neurotrauma results in complex alterations to the biological
      systems within the nervous system, and these changes evolve over time.
      Exploration of the "new nervous system" that follows injury will require methods
      that can both fully assess and simplify this complexity.

PMID- 12803974
TI  - Increased hippocampal CA3 vulnerability to low-level kainic acid following
      lateral fluid percussion injury.
AB  - This study was designed to determine whether a secondary increase in neuronal
      activity induced by a low dose of kainic acid (KA), a glutamate analogue,
      exacerbates the anatomical damage in hippocampal regions following a mild lateral
      fluid percussion (LFP) brain injury. KA (9 mg/kg) was injected intraperitoneally
      in LFP-injured rats (n = 16) 1 h post-trauma. The neuronal loss in the CA3, CA4,
      and hilar regions at 7 days was quantified by two-dimensional cell counts.
      Hippocampal activation 15 min following KA injection was assessed by measuring
      local glucose metabolic rates (lCMR(glc)). Following LFP + KA, the ipsilateral
      side exhibited a 62.7%, 75.7%, and 52.1% decrease in the number of CA3, CA4 and
      hilar neurons, respectively, compared to naive rats (n = 3). These CA3 and CA4
      neuronal counts were also significantly decreased compared to LFP + saline (n =
      5) and sham + KA (n = 9) groups. The median Racine Score, used to rate the
      severity of behavioral seizures, was 4 in LFP + KA and 2 in sham + KA groups (p <
      0.015), suggesting a reduction in seizure threshold following injury. lCMRglc in
      CA3 following LFP + KA was 121.8 +/- 2.0 (mean +/- SE) ipsilaterally and 71.5 +/-
      5.4 contralaterally (p < 0.0012). No changes were found in the BBB permeability
      as measured by [(14)C]aminoisobutyric acid in CA3, CA4, and hilar regions. We
      conclude that the presence of low-level KA 1 h after LFP dramatically increases
      the extent of hippocampal activation and induces a striking loss of ipsilateral
      CA3 and CA4 pyramidal neurons. Neuronal excitation during a time of cellular
      vulnerability may trigger or amplify the cycle of secondary damage in
      functionally impaired, but potentially viable, tissue.

PMID- 12803976
TI  - Age-dependent differences in glutathione peroxidase activity after traumatic
      brain injury.
AB  - Children younger than 4 years old have worse outcome after traumatic brain injury
      (TBI) compared to older children and adults. This increased susceptibility may in
      part be due to differences in the response to oxidative stress. We hypothesized
      that the immature brain does not have an adequate compensatory response to injury
      from oxidative stress. To begin to address this hypothesis, we first compared the
      general dimensions and water content in postnatal day 21 (P21) and adult murine
      brain in the naive state as well as after injury (edema). We examined glutathione
      peroxidase (GPx ) activity in cortical and subcortical regions in P21 and adult
      murine brain following a controlled cortical impact. Brain dimensions including
      areas of the mantle and hemispheres were similar in each of these groups. The
      thickness of the cortical mantle was significantly greater in the immature brain
      as compared to the mature brain (p = 0.01, respectively). Brain edema was
      assessed through changes in water content, and the response to oxidative
      challenge was identified by changes in GPx activity. The P21 brain was similar in
      vulnerability to posttraumatic brain edema when compared to adult. GPx activity
      in the adult brain was increased within 24 h post-injury in the cortex, thalamus
      and hippocampus (ANOVA, p < 0.05), whereas there was no compensatory increase in
      GPx activity in P21 brain, although baseline levels had reached adult levels
      developmentally. These findings support our hypothesis and illuminate the
      important role of oxidative stress after TBI in the immature brain that warrants
      further study.

PMID- 12803977
TI  - Low-dose prostacyclin improves cortical perfusion following experimental brain
      injury in the rat.
AB  - It was recently shown that prostacyclin at a low dose reduces cortical cell death
      following brain trauma in the rat. Conceivably, prostacyclin with its
      vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing
      properties improved a compromised perfusion caused by post-traumatic
      vasoconstriction, microthrombosis and increased microvascular permeability. The
      objective of the present study was therefore to investigate the hemodynamic
      effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid
      percussion brain injury or a sham procedure, animals were treated with a
      continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1),
      or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area
      product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or
      48 h of treatment. Blood flow values in the injured cortex were transiently
      reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma
      from a corresponding value of about 1.6 mL x min(-1) in the sham group, with
      recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent
      increase in blood flow which reached statistical significance 48 h following
      trauma. Brain water content and PS increased in the injured cortex post trauma
      and the higher dose of prostacyclin increased these parameters further at 48 h
      compared to the vehicle group (p < 0.05). The latter effects of prostacyclin
      cannot be attributed to an increase in permeability, as prostacyclin did not
      influence PS or brain water content following sham trauma. In fact prostacyclin
      has been shown to have permeability-decreasing properties. We conclude that
      prostacyclin improves cortical perfusion following brain trauma. The simultaneous
      aggravation of brain edema can be explained by an increased surface area, perhaps
      in combination with increased capillary hydrostatic pressure.

PMID- 12803975
TI  - Temporal alterations in cellular Bax:Bcl-2 ratio following traumatic brain injury
      in the rat.
AB  - Cell death/survival following CNS injury may be a result of alterations in the
      intracellular ratio of death and survival factors. Using immunohistochemistry,
      Western analysis and in situ hybridization, the expression of the anti-cell death
      protein, Bcl-2, and the pro-cell death protein, Bax, was evaluated following
      lateral fluid-percussion (FP) brain injury of moderate severity (2.3-2.6 atm) in
      adult male Sprague-Dawley rats. By 2 h post-injury, a marked reduction of
      cellular Bcl-2-immunoreactivity (IR) and a mild decrease in cellular Bax IR were
      observed in the temporal and occipital cortices, and in the hippocampal CA3
      ipsilateral to the site of impact. These decreases in Bcl-2 and Bax IR appeared
      to precede the overt cell loss in these regions that was evident at 24 h.
      Immunoblot analysis supported the immunohistochemical data, with a modest but
      significant reduction in the intensities of both the Bcl-2 and Bax protein bands
      at 2 h (p < 0.05 compared to sham levels). However, the Bax:Bcl-2 ratio increased
      significantly at 2 h (2.28 +/- 0.13) and remained elevated up to 7 days (2.05 +/-
      0.13) post-injury compared to sham-injured control tissue (1.62 +/- 0.10, p <
      0.05). Furthermore, cortical, but not hippocampal, levels of Bax protein
      increased by 25% (p < 0.05 compared to sham-injured controls) at 24 h post
      injury, and returned to control levels by 7 days. In situ hybridization analysis
      of Bax mRNA revealed increased cellular grain density in the injured cortex (p <
      0.05 compared to sham-injured brains), but not in the CA3 region of the injured
      hippocampus. No injury-induced changes in the expression of Bcl-2 mRNA were
      observed in any brain region. Taken together, these data suggest that the
      association between regional post-traumatic cell death and alterations in the
      cellular ratio of Bcl-2 and Bax may be, in part, due to alterations in mRNA
      and/or protein expression of the Bcl-2 family of proteins.

PMID- 12803979
TI  - Patient selection for clinical trials: the reliability of the early spinal cord
      injury examination.
AB  - Patients with incomplete spinal cord injuries can spontaneously recover motor
      function. Because of this, phase I and II trials of invasive interventions for
      acute spinal cord injury will likely involve neurologically complete injuries. It
      is therefore important to reliably identify complete injuries as early as
      possible. We examined the reliability of the early examination in motor complete
      spinal cord injuries by retrospectively analyzing the stability of baseline
      neurological status determined within 2 days of injury in 103 subjects. Baseline
      neurological status was compared to neurological status at follow-up, preferably
      within one week (101 of 103 subjects). When available (n = 68), neurological
      status at 1 year or later was also compared. Overall, 6.2% (5/81) of motor
      complete, sensory complete (ASIA A) subjects converted to motor complete, sensory
      incomplete status (ASIA B) between the initial and follow-up assessments;
      however, none exhibited motor recovery (ASIA C or D). At initial follow-up, 9.3%
      (4/43) of ASIA A subjects with factors affecting examination reliability were
      reclassified as ASIA B injuries compared to 2.6% (1/38) of ASIA A subjects
      without such factors. At year 1 or later, 6.7% (2/30) of ASIA A subjects without
      factors affecting exam reliability, converted to ASIA B status. None developed
      volitional motor function below the zone of injury. For subjects with factors
      affecting exam reliability, 17.4% (4/23) of ASIA A subjects converted to
      incomplete status and 13.0% (3/23) regained some motor function by one year or
      later (ASIA C or D). These data suggest that it is possible to identify within 48
      h of injury, a subset of patients with a negligible chance for motor recovery who
      would be suitable candidates for future clinical trials of invasive treatments.

PMID- 12803978
TI  - A novel dehydroepiandrosterone analog improves functional recovery in a rat
      traumatic brain injury model.
AB  - The purpose of this study was to investigate the efficacy of a novel steroid,
      fluasterone (DHEF, a dehydroepiandrosterone (DHEA) analog), at improving
      functional recovery in a rat model of traumatic brain injury (TBI). The lateral
      cortical impact model was utilized in two studies of efficacy and therapeutic
      window. DHEF was given (25 mg/kg, intraperitoneally) at the initial time point
      and once a day for 2 more days. Study A included four groups: sham injury,
      vehicle treated (n = 22); injured, vehicle treated (n = 30); injured, pretreated
      (5-10 min prior to injury, n = 24); and injured, posttreated (initial dose 30 min
      postinjury, n = 15). Study B (therapeutic window) included five groups: sham
      injury, vehicle treated (n = 17); injured, vehicle treated (n = 26); and three
      posttreatment groups: initial dose at 30 min (n = 18), 2 h (n = 23), or 12 h (n =
      16) postinjury. Three criteria were used to grade functional recovery. In study
      A, DHEF improved beam walk performance both with pretreatment (79%) and 30-min
      posttreatment group (54%; p < 0.01, Dunnett vs. injured vehicle). In study B, the
      12-h posttreatment group showed a 97% improvement in beam walk performance (p <
      0.01, Dunnett). The 30-min and 12-h posttreatment groups showed a decreased
      incidence of falls from the beam, which reached statistical significance (p <
      0.05, Dunnett). Tests of memory (Morris water maze) and neurological reflexes
      both revealed significant improvements in all DHEF treatment groups. In cultured
      rat mesangial cells, DHEF (and DHEA) potently inhibited interleukin-1beta-induced
      cyclooxygenase-2 (COX2) mRNA and prostaglandin (PGE2) production. In contrast,
      DHEF treatment did not alter injury-induced COX2 mRNA levels in the cortex or
      hippocampus. However, DHEF (and DHEA) relaxed ex vivo bovine middle cerebral
      artery preparations by about 30%, with an IC(50) approximately 40 microM. This
      was a direct effect on the vascular smooth muscle, independent of the endothelial
      cell layer. Fluasterone (DHEF) treatments improved functional recovery in a rat
      TBI model. Possible mechanisms of action for this novel DHEA analog are
      discussed. These findings suggest an exciting potential use for this agent in the
      clinical treatment of traumatic brain injury.

PMID- 12803980
TI  - Morphological characterization of photochemical graded spinal cord injury in the
      rat.
AB  - This study characterizes the histological and immunohistochemical changes in the
      adult rat spinal cord following photochemically induced spinal cord lesions. The
      spinal cord was exposed by laminectomy (T12-L1 vertebrae) and bathed with 1.5%
      rose bengal solution for 10 min. The excess dye was removed by saline rinse and
      the spinal cord was irradiated with "cold" light for 0, 1, 2.5, 5, and 10 min in
      different groups of rats. After 15 days a graded loss of spinal tissue was
      observed according to photoinduction times. Animals irradiated for 1 min showed
      spinal cavities involving the dorsal funiculi. The cavity became progressively
      larger, involving dorsal horns in animals irradiated for 2.5 min, together with
      the dorsolateral funiculi in animals irradiated for 5 min and the ventrolateral
      funiculi in those irradiated for 10 min, with loss of gray matter in these three
      groups. Changes in GFAP-, CGRP-, proteoglycan- and calbindin-immunoreactivity
      were observed in all lesioned groups when compared with control spinal cords.
      Hypertrophied and heavily GFAP- and proteoglycan-stained astrocytes were seen in
      irradiated spinal cords. Reactive microglial cells were also found. Both
      astroglial and microglial reactions paralleled the severity of the spinal cord
      lesion. A significant loss of CGRP-immunoreactive somas was seen in animals
      irradiated for 10 min, whereas the wider distribution of calbindin-positive
      neurons was found in lesioned rats. In spinal cord sections from animals
      illuminated for 5 min and perfused 60 min postillumination, light and electron
      microscopy showed cytotoxic edema with astrocytic swelling, red blood cell
      extravasation, and myelin degradation.

PMID- 12803981
TI  - Functional and electrophysiological characterization of photochemical graded
      spinal cord injury in the rat.
AB  - This study characterizes by functional and electrophysiological methods changes
      following photochemically induced injuries to the spinal cord in adult rats. The
      spinal cord was exposed by laminectomy and bathed with 1.5% rose bengal solution
      for 10 min (T12-L1 vertebrae). The excess dye was removed by saline rinse and the
      spinal cord was irradiated with "cold" light for 0, 1, 2.5, 5, and 10 min in
      different groups of rats. During the first 15 days postlesion, locomotion
      activity, pain sensibility, motor and somatosensory evoked potentials, and motor
      and nerve action potentials were evaluated. Graded locomotor and nociceptive
      recovery was observed in irradiated rats depending on the photoinduction time. At
      15 days, the amplitude of motor and sensory evoked potentials was significantly
      lower in irradiated groups with respect to control rats. The amplitude of
      compound muscle action potentials and of reflex H wave after sciatic nerve
      stimulation decreased significantly in irradiated animals with respect to control
      rats, while the latency did not show significant differences. In irradiated
      groups, significant differences were seen between pre- and postoperative values
      for most functional and electrophysiological parameters analyzed. A significant
      negative relationship was found between the area of cystic cavity of the spinal
      cord and the functional and electrophysiological impairment.

PMID- 12803982
TI  - Postischemic hypothermia inhibits the generation of hydroxyl radical following
      transient forebrain ischemia in rats.
AB  - A small reduction of body temperature during reperfusion following cerebral
      ischemia has been known to ameliorate neuronal injury. However, the mechanisms
      underlying postischemic hypothermia-induced neuroprotection are poorly
      understood. The burst of reactive oxygen species (ROS) formation that occurs
      during reperfusion has been documented to be involved in ischemic neuronal
      degeneration. In this study, we investigated the effect of postischemic
      hypothermia on ROS production following transient forebrain ischemia using an in
      vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid
      artery occlusion combined with hemorrhagic hypotension for 20 min in male Wistar
      rats. The body temperature was kept at 37 degrees C during ischemia and
      controlled at either 32 degrees C or 37 degrees C after reperfusion. The amount
      of hydroxyl radical produced in striatum was evaluated by measurement of 2,3- and
      2,5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation.
      We also measured the extracellular concentration of xanthine, while determining
      striatal blood flow by the hydrogen clearance technique. In animals whose
      postischemic body temperature was maintained at 37 degrees C, the levels of 2,3-
      and 2,5-DHBA significantly increased after reperfusion. The peak levels of 2,3-
      and 2,5- DHBA were 2.9-fold and 2.7-fold increased above the corresponding
      baseline values, respectively. Postischemic hypothermia completely inhibited the
      hydroxyl radical formation. Likewise, xanthine formation was also inhibited by
      postischemic hypothermia. In contrast, striatal cerebral blood flow was not
      altered by temperature modulation during reperfusion. These results suggest that
      inhibition of ROS production accompanied with suppression of xanthine formation
      is implicated in the neuroprotection of postischemic hypothermia.

PMID- 12803984
TI  - Laparoscopic radical nephrectomy: financial disincentives by the Health Care
      Financing Administration.
AB  - BACKGROUND AND PURPOSE: Laparoscopic radical nephrectomy is a minimally invasive
      alternative to open radical nephrectomy. We have noticed that since the beginning
      of 2001, when the Current Procedural Terminology (CPT) code 50545 became
      available for laparoscopic nephrectomy, the reimbursement for the laparoscopic
      operation was significantly lowered. This led us to survey 25 laparoscopic
      urologic surgeons to assess trends in reimbursement from all over the United
      States. MATERIALS AND METHODS: During this period, the records of reimbursements
      for radical nephrectomy were available from a single practice to compare that for
      the open and laparoscopic techniques. The 19 open and 10 laparoscopic operations
      were entered in a database for statistical analysis. Endourologists around the
      country also were polled on the subject. RESULTS: The average reimbursement for
      an open radical nephrectomy was $1581 +/- 325 (SD), while the average
      reimbursement for a laparoscopic radical nephrectomy was $1192 +/- 184. Twenty
      five polled endourologists had noted similar reductions in reimbursement for
      laparoscopic procedures. Many of those polled had participated in the Specialty
      Society Relative Value Unit (RVU) survey for laparoscopic radical nephrectomy and
      stated that their recommendations were that the value be considered greater than
      that of the open counterpart. CONCLUSION: The highly significant difference in
      reimbursement reflects a financial disincentive to surgeons performing
      laparoscopic procedures. It is obvious that in the U.S., the Health Care
      Financing Administration (now the Centers for Medicare and Medicaid Services) is
      devaluating all surgical procedures, and financial pressures of this type are
      disturbing.

PMID- 12803985
TI  - Is telesurgery a new reality? Our experience with laparoscopic and percutaneous
      procedures.
AB  - BACKGROUND: Minimally invasive surgery offers many advantages, but its correct
      practice is associated with a steep learning curve. Telesurgery allows a surgeon
      at a remote site to guide and teach surgeons at a primary site by utilizing
      robotic devices, telecommunications, and video technology, thereby reducing
      complications. PATIENTS AND METHODS: From September 1998 to July 2000, 17
      procedures were telementored between two sites 9230 km apart: a primary operating
      room at the Policlinico Casilino "Tor Vergata" University of Rome and a remote
      site at the Johns Hopkins Medical Institutions in Baltimore. Of these procedures,
      14 were laparoscopic cases: 8 spermatic vein ligations, 2 retroperitoneal renal
      biopsies, 3 simple nephrectomies, and 1 pyeloplasty. Three procedures were
      carried out to obtain percutaneous renal access. All procedures were performed
      with the help of two robots: the first robot, AESOP, for the orientation of the
      laparoscope, and the second one, PAKY, to perform the percutaneous renal access.
      In addition to the robotic device, the system provided four ISDN lines, a PC with
      dedicated software to manage the connection, audio and video connections, an
      external video camera with a panoramic view of the operating room, and remote
      control of the electrocautery and the Telestrator. RESULTS: All the procedures
      were accomplished with an uneventful postoperative course. Ten operative cases
      were telementored successfully. In five cases, it was not possible to establish a
      connection to the remote site, and two procedures were converted to open surgery
      because of intraoperative complications. The time delay of the image transmission
      was <1 second. CONCLUSION: This preliminary experience has demonstrated the
      feasibility of international telementoring. It could provide education to
      surgeons and decrease the likelihood of complications attributable to
      inexperience with new techniques.

PMID- 12803986
TI  - Technical evolution of laparoscopic radical prostatectomy after 450 cases.
AB  - BACKGROUND AND PURPOSE: In 1998, laparoscopic radical prostatectomy with primary
      access to the seminal vesicles was introduced. In 1999, we developed a
      laparoscopic technique similar to the classic retropubic radical prostatectomy.
      We focus here on the continuous technical evolution of our technique. PATIENTS
      AND METHODS: From March 1999 to May 2002, we performed 450 laparoscopic radical
      prostatectomies. All important data of the patients; data concerning the
      performance of the procedure, including technical modifications, conversion,
      reintervention, and complication rate; as well as follow-up information were
      documented contemporaneously. The patients were divided into three groups of 150
      individuals each in order to analyze the influence of the technical evolution of
      the procedure. Additionally, we studied the transferability of our technique,
      comparing the learning curves of the three surgeons involved in the program.
      RESULTS: The technical modifications included the routine use of a voice
      controlled robot (AESOP) for the camera, exposure of the apex with 120 degrees
      retracting forceps, a free-hand suturing technique instead of the Endostitch
      device for the dorsal vein complex, 5-mm clipping instead of bipolar coagulation
      for the nerve-sparing technique, initial 6 o'clock suturing of the urethra before
      complete division, control of the prostatic pedicles by use of 12-mm Hemo-lok
      clips instead of the Ultracision or Endo-GIA, the bladder neck-sparing technique
      in cases of T(1c) and T(2a) tumors, and interrupted instead of continuous sutures
      for the vesicourethral anastomosis. All these modifications resulted in a
      significant decrease in operating time and the rates of transfusion, open
      conversion, and reintervention. The introduction of the nerve-sparing technique
      increased the number of tumor-positive margins. The mean operating time of the
      third surgeon was significantly less than that of the first surgeon, but the
      transfusion, conversion, and reintervention rates did not differ significantly
      among the surgeons. CONCLUSIONS: Laparoscopic radical prostatectomy has undergone
      continuous technical evolution resulting in a significant improvement of the
      operative results. Although we were able to demonstrate the transferability of
      this difficult procedure, we feel that it should be performed only at centers of
      expertise.

PMID- 12803987
TI  - Single-center comparison of laparoscopic pyeloplasty, Acucise endopyelotomy, and
      open pyeloplasty.
AB  - PURPOSE: To compare Acucise endopyelotomy (Applied Medical, Irvine, California),
      laparoscopic pyeloplasty, and open pyeloplasty in the treatment of ureteropelvic
      junction (UPJ) obstruction. PATIENTS AND METHODS: A retrospective review of all
      adult patients undergoing surgical correction of UPJ obstruction between December
      1999 and August 2001 at Vanderbilt University Medical Center was performed.
      Patients undergoing UPJ correction with Acucise endopyelotomy (N = 9),
      laparoscopic pyeloplasty (N = 16), and open pyeloplasty (N = 7) were compared in
      regard to demographic information, operative data, recovery parameters, cost
      data, and outcome (as determined by diuretic renography, the Whitaker test, or
      both). RESULTS: Success rates of 56%, 94%, and 86% were obtained for Acucise
      endopyelotomy, laparoscopic pyeloplasty, and open pyeloplasty, respectively.
      There were no differences between the Acucise endopyelotomy and laparoscopic
      pyeloplasty groups in age, American Society of Anesthesiology (ASA) score, length
      of follow-up, estimated blood loss (EBL), hospital stay, total hospital cost, or
      analgesic requirement. The Acucise patients demonstrated shorter operating times
      (1.7 v 3.3 hours; P < 0.001) and time to oral intake (7.9 v 16 hours; P = 0.008)
      than the laparoscopic pyeloplasty group. When the laparoscopic pyeloplasty
      patients were compared with the open pyeloplasty patients, there was no
      difference in operative time, EBL, time to oral intake, or total hospital costs.
      The laparoscopically treated patients demonstrated significantly lower analgesic
      requirements (27.2 v 124.2 mg of morphine sulfate equivalent; P = 0.02) and
      shorter hospital stays (1.4 v 3.0 days; P = 0.03) than the open surgery patients.
      The Acucise patients demonstrated shorter operative time (1.7 v 3.4 hours; P <
      0.001), shorter hospital stay (1.3 v 3.0 days; P = 0.02), and lower analgesic
      requirement (22.4 v 124.2 mg of morphine sulfate equivalent; P = 0.02) than the
      open surgery patients. CONCLUSIONS: Laparoscopic pyeloplasty achieves a success
      rate equal to that of open pyeloplasty while providing a recovery similar to that
      obtained with Acucise endopyelotomy and is gaining popularity as the treatment of
      choice for UPJ obstruction.

PMID- 12803988
TI  - Single-center comparison of purely laparoscopic, hand-assisted laparoscopic, and
      open radical nephrectomy in patients at high anesthetic risk.
AB  - BACKGROUND AND PURPOSE: The laparoscopic approach for management of high-risk
      patients with renal-cell carcinoma (RCC) may reduce perioperative and
      postoperative morbidity. The aim of this study was to compare the outcome of
      purely laparoscopic radical nephrectomy (LRN), hand-assisted laparoscopic radical
      nephrectomy (HALRN), and open radical nephrectomy (ORN) for renal tumors in a
      population of patients at high risk for perioperative complications. PATIENTS AND
      METHODS: All patients undergoing radical nephrectomy for presumed RCC between
      August 1999 and August 2001 at Vanderbilt University Medical Center and having an
      American Society of Anesthesiologists (ASA) score of >/=3 were reviewed. Patients
      with known metastasis, local invasion, caval thrombi, or additional simultaneous
      surgical procedures were excluded from analysis. Thirteen patients underwent LRN,
      eight patients underwent HALRN, and 26 underwent ORN. The patient demographics
      were similar in the three groups. The groups were compared with regard to
      intraoperative and postoperative parameters. Statistical analysis was done using
      chi-square testing for categorical variables and analysis of variance (ANOVA) for
      continuous variables. Differences in outcomes were examined using ANOVA and
      Dunnett's T for pairwise comparisons. RESULTS: The ASA 4 patients had
      significantly longer hospital stays and total hospital costs than the ASA 3
      patients. The mean operative time in the ASA 3 patients was similar in the three
      groups: 2.8 hours, 2.8 hours, and 2.5 hours for the LRN, HALRN, and ORN patients,
      respectively. Both the LRN patients (22.9 mg of morphine sulfate equivalent) and
      the HALRN patients (42.1 mg) required less pain medication than the open surgery
      patients (97.7 mg). When the total hospital costs were compared, LRN was less
      costly than HALRN ($6089 v $7678; P = 0.57) and open surgery ($6089 v $7694; P =
      0.04). The complication rate in the LRN, HALRN, and ORN group was 0%, 25%, and
      27%, respectively, although the differences were not statistically different (P =
      0.12). CONCLUSIONS: Both LRN and HALRN can be performed safely in patients with
      significant comorbid conditions. Careful preoperative preparation, intraoperative
      monitoring, and awareness of laparoscopy-induced oliguria can preclude
      inadvertent overhydration, hemodilution, and congestive heart failure. Both LRN
      and HALRN result in less pain medication requirement and faster return to oral
      intake than ORN, and LRN results in fewer perioperative complications than HALRN
      or ORN in patients at high perioperative risk. The LRN technique has a 21% lower
      total cost than both HALRN and ORN.

PMID- 12803989
TI  - Phase I trial of a temporary ureteral drainage stent.
AB  - BACKGROUND AND PURPOSE: The temporary ureteral drainage stent (TUDS; Boston
      Scientific/Microvasive, Natick, MA) is a biodegradable device that is designed to
      maintain patency for 48 hours with gradual softening and spontaneous expulsion
      thereafter. We evaluated the durability, patency, and safety of TUDS in a Phase I
      clinical trial. PATIENTS AND METHODS: Eighteen stone patients requiring
      sequential percutaneous nephrolithotomies (PNL) for complex stone disease
      underwent antegrade TUDS placement following initial percutaneous treatment.
      Nineteen devices were placed in 21 attempts, with one patient undergoing
      bilateral TUDS placement. Day 2 nephrostograms were performed to allow assessment
      of stent status and to demonstrate antegrade flow. Stents were removed at the
      time of the secondary PNL (day 2 or 3). RESULTS: No complications occurred during
      TUDS placement. On day 2, 1 stent had passed into the bladder. Eleven stents were
      completely intact, with seven others partially intact. Day 2 ureteral patency was
      demonstrated in all 19 stented ureters. Eighteen TUDS were removed completely
      during the secondary PNL with one incident of partial retention. All stent
      material had passed out of the body in all patients by 1 month. No adverse events
      were attributable to the TUDS. CONCLUSIONS: The TUDS appears to facilitate
      ureteral drainage for at least 48 hours after placement. Although occasional
      stent tail detachments were noted, these did not interfere with device function.
      The safety profile of TUDS was favorable, with no complications attributable to
      the device itself. A larger prospective clinical study in patients receiving TUDS
      placed retrograde after uncomplicated ureteroscopic manipulation appears
      appropriate on the basis of these initial findings.

PMID- 12803990
TI  - Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers
      and its relation to urinary oxalate.
AB  - BACKGROUND AND PURPOSE: Oxalobacter formigenes is an anaerobic commensal colonic
      bacterium capable of degrading oxalate through the enzyme oxalyl-CoA
      decarboxylase. It has been theorized that individuals who lack this bacterium
      have higher intestinal oxalate absorption, leading to a higher urinary oxalate
      concentration and an increased risk of calcium oxalate urolithiasis. We performed
      a prospective, controlled study to evaluate O. formigenes colonization in calcium
      oxalate stone formers and to correlate colonization with urinary oxalate and
      other standard urinary stone risk factors. PATIENTS AND METHODS: Thirty-five
      first-time calcium oxalate stone formers were compared with 10 control subjects
      having no history of urolithiasis and a normal renal ultrasound scan. All
      subjects underwent standard metabolic testing by submitting serum and 24-hour
      urine specimens. In addition, all subjects submitted stool samples for culture
      and detection of O. formigenes by Xentr(ix) O. formigenes Monitor. RESULTS:
      Intestinal Oxalobacter was detected in only 26% of the stone formers compared
      with 60% of the controls (p < 0.05). Overall, the average urinary oxalate
      excretion by the two groups was similar (38.6 mg/day v 40.8 mg/day). Among stone
      formers, however, there were statistically higher urinary oxalate concentrations
      in O. formigenes-negative patients compared with those testing positive (41.7
      mg/day v 29.4 mg/day) (p = 0.03). Furthermore, all 10 stone formers with
      hyperoxaluria (>44 mg/day) tested negative for O. formigenes (p < 0.05).
      CONCLUSIONS: Calcium oxalate stone formers have a low rate of colonization with
      O. formigenes. Among stone formers, absence of intestinal Oxalobacter correlates
      with higher urinary oxalate concentration and an increased risk of hyperoxaluria.
      Introduction of the Oxalobacter bacterium or an analog of its enzyme oxalyl-CoA
      decarboxylase into the intestinal tract may be a treatment for calcium oxalate
      stone disease.

PMID- 12803991
TI  - In vitro analysis of stone fragmentation ability of the FREDDY laser.
AB  - BACKGROUND AND PURPOSE: The Frequency-Doubled Double-Pulse Nd:Yag) (FREDDY) laser
      (World of Medicine, Berlin Germany) is a short-pulsed, double-frequency solid
      state laser with wavelengths of 532 and 1064 nm. This low-power, low-cost laser
      was developed for intracorporeal lithotripsy. We designed an experimental set-up
      to test its fragmentation efficiency at different energy and frequency settings.
      MATERIALS AND METHODS: Forty previously weighed plaster-of-Paris stone phantoms
      were divided into four groups in order to test fragmentation at 5 and 10 Hz for 2
      and 4 minutes. A hands-off underwater laboratory set-up including a holder to
      keep the stone phantom in contact with the quartz laser fiber was utilized. The
      280-microm laser fiber was cleaved and stripped between runs to ensure optimal
      energy delivery. After fragmentation was completed, all of the stone fragments
      remaining within the holder were allowed to desiccate for 48 hours and reweighed.
      Fragmentation was measured as the percentage weight loss. RESULTS: Stone phantoms
      fragmented at 5 Hz for 2 minutes sustained a mean 24% loss of weight, whereas the
      4-minute treatment at 5 Hz reduced stone weight by 54%. Treatment at 10 Hz for 2
      minutes demonstrated results similar to those of stones treated for 4 minutes at
      5 Hz, reducing stone weight by 51%. Fragmentation at 10 Hz for 4 minutes revealed
      a 64% loss of mass, less than expected for these power settings. Fiber
      deterioration observed at the higher energy settings may be the cause of the
      reduced stone-fragmentation efficiency. CONCLUSIONS: Fragmentation with the
      FREDDY laser in the 5 Hz, 4 minutes and 10 Hz, 2 minutes protocols is comparable,
      suggesting that stone fragmentation correlates well with the total energy
      delivered to the stone. The slight drop in fragmentation efficiency at 10 Hz, 4
      minutes is most likely explained by fiber damage occurring consistently at these
      higher energy settings. The safety profile and low investment and running costs
      of this laser are advantages that suggest the laser warrants further clinical
      trials.

PMID- 12803992
TI  - Use of bipolar laparoscopic forceps to occlude and transect the retroperitoneal
      vasculature: a porcine model.
AB  - BACKGROUND AND PURPOSE: Surgical clips are commonly employed during laparoscopic
      radical nephrectomy to ligate perihilar vessels reliably, yet these clips can
      interfere with the application of a vascular stapler to major vessels,
      potentially leading to catastrophic hemorrhage. We assessed the efficacy of the
      PlasmaKinetic trade mark (PK) bipolar cutting forceps (Gyrus Medical,
      Minneapolis, MN) as a single modality in coagulating and dividing the
      retroperitoneal vessels in a swine model. MATERIALS AND METHODS: Three 40- to 50
      kg domestic swine (six renal units) underwent celiotomy and retroperitoneal
      exposure. The inferior vena cava (IVC) and the renal, gonadal, and iliac vessels
      were isolated, and, using 5- and 10-mm forceps, coagulated and divided. The mean
      diameter of the renal vein was 8.7 mm, the renal artery 6.5 mm, and the IVC 14
      mm. RESULTS: Hemostasis was achieved consistently using the 5-mm and 10-mm PK
      Cutting Forceps on the renal artery, renal vein, and gonadal vein. The 10-mm
      forceps coagulated the iliac veins and IVC 83% of the time with only a single
      application. Larger vessels or vessels with higher inherent vascular pressure
      required additional applications of the device to achieve hemostasis. All animals
      were hemodynamically stable through division of the IVC, as measured by heart
      rate and pulse oximetry. No complications were noted with the device or using the
      cutting element. CONCLUSIONS: The PK bipolar cutting forceps appear to be
      effective in controlling and dividing the renal hilar vessels and larger low
      pressure vessels of the porcine retroperitoneum, with no gross damage to adjacent
      structures. Although further studies are necessary before use during laparoscopic
      nephrectomy in humans, these results are promising. Bipolar cutting forceps may
      prove to be a safe, cost-effective, and time-saving device with numerous
      applications during urologic laparoscopy.

PMID- 12803993
TI  - Fluorescence resonance energy transfer analysis of the RANTES polymorphisms -403G
      --> A and -28G --> C: evaluation of both variants as susceptibility factors to
      HIV type 1 infection in the Spanish population.
AB  - The identification of genetic factors predisposing or protecting against HIV-1
      infection has been an important aim in AIDS research. Two of these factors are
      located in the promoter region of the CCL5 gene, which encodes the RANTES
      (regulated on activation, normal T cells expressed and secreted) chemokine, an
      inhibitor agent for M-tropic HIV-1 strains. More specifically, the role of single
      nucleotide polymorphisms (SNPs) -403G --> A and -28C --> G has been evaluated in
      the course of HIV-1 infection in several populations with different genetic,
      geographic, and ethnic backgrounds. Here we present a fast, simple, reliable, and
      efficient method for the simultaneous genotyping of these two CCL5 variants. A
      case-control study has been performed to evaluate the role of -403G --> A and 
      28C --> G as susceptibility factors for HIV-1 infection in the Spanish
      population. No differences have been found in the allelic frequencies of either
      variant or in the haplotype/genotype distribution between patients and controls.
      These data would be consistent with a lack of association between these SNPs and
      HIV-1 infection in our population.

PMID- 12803994
TI  - Identification of a transmission chain of HIV type 1 containing drug resistance
      associated mutations.
AB  - We have investigated a potential transmission chain of HIV-1 with drug resistance
      associated mutations between three individuals over a period of 5 years by use of
      cloning and sequencing of viral genes, and phenotypic characterization. Viruses
      containing reverse transcriptase drug resistance-associated mutations were
      transmitted sequentially between three homosexual men (A, B, and C), and
      persisted in one individual for at least 4 years, despite intermittent therapy
      and reduced viral replicative capacity compared with wild-type strains. Clonal
      analysis of the envelope gene from semen and blood virus showed that the virus
      transmitted to patient C was more closely related to virus from the semen than
      the blood of patient B. Our data suggest that HIV variants with drug resistance
      associated mutations can persist following primary infection, despite intervening
      antiretroviral therapy, and subsequently sexually transmitted. We provide "proof
      of principle" that such mutations can therefore become "fixed" within the
      circulating virus pool.

PMID- 12803995
TI  - Rate, causes, and clinical implications of presenting with low CD4+ cell counts
      in the era of highly active antiretroviral therapy.
AB  - Of patients attending HIV clinics, neither the proportion with CD4(+) cell counts
      below 200 cells/microl, and therefore at risk for developing opportunistic
      infections (OIs), nor the reasons for the persistence of low CD4(+) cell counts
      are well known in the era of highly active antiretroviral therapy (HAART). In an
      effort to gather data concerning this issue, the charts of all outpatients who
      attended two reference HIV clinics in Spain throughout the year 2001 were
      retrospectively reviewed. Of 1897 subjects, 213 (11%) had at least one CD4(+)
      cell count determination below 200 cells/microl during 2001. The main reasons for
      presenting with low CD4(+) cell counts were as follows: (1) poor treatment
      adherence, 64 (30%); (2) poor immune recovery despite complete virus suppression
      for longer than 1 year on HAART, 47 (22%); (3) virologic failure under HAART, 33
      (15%); (4) no antiretroviral therapy, 23 (11%); (5) initiation of HAART within
      the current year in subjects with very low CD4(+) cell counts, 17 (8%); (6)
      impediment in using HAART due to toxicity, 17 (8%); and (7) drug-induced
      myelotoxicity, 12 (6%). During the period under review, one or more OIs developed
      in 52 of the 213 (24%) patients with low CD4(+) cell counts. They occurred more
      frequently in subjects who were naive for antiretroviral drugs or who initiated
      therapy recently (RR, 6.45; 95% CI, 2.43-17.12; p < 0.001), and conversely tended
      to be less frequent among subjects with poor immune reconstitution despite
      complete virologic suppression while on HAART (RR 0.86; 95% CI, 0.28-2.62; p =
      0.79). A lower lifetime CD4(+) cell count nadir was associated with a greater
      risk of developing an OI (RR, 0.98; 95% CI, 0.97-0.99; p < 0.001). We conclude
      that, despite the availability of HAART, more than 10% of patients currently
      attending HIV clinics have CD4(+) cell counts <200 cells/microl, and continue to
      be at risk for developing OIs. Poor treatment adherence and lack of immune
      recovery despite complete virus suppression while on HAART account for more than
      half of cases.

PMID- 12803996
TI  - Patterns of gene expression in peripheral blood mononuclear cells of rhesus
      macaques infected with SIVmac251 and exhibiting differential rates of disease
      progression.
AB  - Using the Affymetrix HuGeneFL GeneChip, the global expression patterns of genes
      in the peripheral blood mononuclear cells (PBMCs) of rhesus macaques, infected
      with SIVmac251 and exhibiting rapid, typical, or slow rates of disease
      progression, were examined. Assessments of the change in gene expression (fold
      change), the temporal coordination of gene expression (self-organizing map
      analysis), and the similarities and significant differences in gene expression
      across the groups were performed on samples taken before infection and 3 and 7
      weeks postinfection. An upregulation of the p27 interferon-inducible gene and of
      genes associated with cellular activation and immune response was observed in all
      three groups. Rapidly progressing animals exhibited a modest number of genes with
      a change in expression of 3-fold or greater, typically progressing animals
      exhibited the greatest number, and slowly progressing animals exhibited the
      fewest. Self-organizing map cluster analysis indicated that rapidly progressing
      animals exhibited the least coordinated gene expression over the three study time
      points, typically progressing animals exhibited a moderate degree, and animals
      with slow progression exhibited the most coordinated gene expression. Mann
      Whitney U analysis indicated that differences in gene expression were most
      pronounced between the rapidly and slowly progressing groups and least pronounced
      between the rapidly and typically progressing animals. These observations
      elucidate distinct features of gene expression in animals with different rates of
      disease progression.

PMID- 12803997
TI  - Early viral load and CD4+ T cell count, but not percentage of CCR5+ or CXCR4+
      CD4+ T cells, are associated with R5-to-X4 HIV type 1 virus evolution.
AB  - HIV-1 infection is established by CCR5-utilizing (R5) variants, and CXCR4
      utilizing (X4) variants emerge in approximately 50% of infected patients. We
      studied the role of CCR5 and CXCR4 expression before and 1 and 5 years after
      seroconversion in HIV-1 disease in a prospective study of 102 seroconverters.
      High percentages of CCR5(+) cells among total cells (relative hazard [RH], 2.55;
      95% confidence interval [95% CI], 0.99-6.52), but not among CD45RO(-)CD4(+) and
      CD45RO(+)CD4(+) cells preseroconversion and among total cells and CD45RO(-)CD4(+)
      cells (RH, 2.70; 95% CI, 1.06-6.92 and RH, 3.54; 95% CI, 1.27-9.90, respectively)
      5 years after seroconversion were associated with more rapid progression to AIDS.
      One year after seroconversion, high percentages of CXCR4(+) cells among total and
      CD45RO(-)CD4(+) cells were associated with delayed development of X4 variants
      (RH, 0.49; 95% CI, 0.20-1.21 and RH, 0.41; 95% CI, 0.17-1.02, respectively),
      whereas no association was observed for the percentage of CCR5(+) cells. In a
      larger study population, high early serum viral RNA and low CD4(+) T cell numbers
      were associated with more rapid development of X4 variants. Our results exclude
      target cell availability as a driving force for R5-to-X4 virus phenotype
      evolution.

PMID- 12803998
TI  - The relationships between substance abuse, psychosocial variables, and natural
      killer cell enumeration and function in HIV-infected and high-risk uninfected
      adolescents.
AB  - This report examines the relationship between substance use, psychosocial
      stressors, and natural killer (NK) cell enumeration and function in HIV-infected
      and high-risk uninfected adolescents. We studied the association of demographic
      characteristics; self-report measures of alcohol, tobacco, and marijuana use; and
      self-report measures of psychosocial stressors (depressive symptoms, anxiety)
      with three immune outcomes: NK (CD3(-)CD16(+)CD56(+)) absolute counts, lytic
      units per peripheral blood mononuclear cells (PBMCs), and lytic units per NK
      cell. In addition, we determined the association of HIV disease stage,
      antiretroviral therapy (ART), CD4(+) T-cell count, and viral load with these
      outcomes in the subset of HIV-infected adolescents. METHODS: This cross-sectional
      analysis reports on data collected during a longitudinal observational study of
      adolescents (the REACH Study). A cross-sectional analysis was performed with data
      from the first visit for each subject that met criteria for concurrent (within 3
      days) assessment of NK number and function, substance use, and psychosocial data.
      The data set represented 501 subjects. Analyses were performed separately for the
      HIV-seropositive and seronegative adolescents. In the HIV-seronegative
      population, there were no significant predictors of NK cell count and only female
      gender was significantly associated with CD3(-)CD16(+)CD56(+) NK lytic units per
      PBMC. Analysis of the HIV-seronegative cohort also showed that black race was
      significantly associated with higher lytic units per NK cell. RESULTS: In HIV
      seropositive adolescents, we observed an association of female gender with lower
      NK cell number and lytic units per PBMC, but not with lytic units per NK cells.
      Current use of one or two antiretroviral drugs was predictive of lower NK
      numbers. This drug effect was also noted in the functional assay per PBMC but not
      per NK cell. Increasing worry scores and no marijuana use over the past 3 months
      were associated with lower functional NK measures per PBMC in HIV-seropositive
      youth. Laboratory-confirmed recent marijuana use was highly predictive of
      increased lytic activity calculated per NK cell. These effects were not observed
      in similar analyses of data from HIV-seronegative adolescents. Depressive
      symptoms, assessed with an epidemiologic screening tool, were not found to be
      predictive of NK cell number or function in either the HIV-seronegative or the
      HIV-seropositive subset. These findings document associations between substance
      abuse, psychosocial variables, and NK numbers and function in adolescents.

PMID- 12803999
TI  - Enhancement of immune responses to an HIV env DNA vaccine by a C-terminal segment
      of listeriolysin O.
AB  - An effective vaccine against AIDS should induce both cellular and humoral immune
      responses. Here we report that immunization of mice with a DNA plasmid encoding a
      chimeric protein consisting of HIV89.6 Env gp140 and the listeriolysin O (LLO) C
      terminal segment (59 amino acids) significantly enhanced both humoral and
      cellular immune responses against the HIV89.6 Env protein. Plasmid DNA expression
      vectors with genes codon-optimized for mammalian expression were synthesized for
      HIV89.6 gp140 as well as for chimeric protein gp140-LLO, in which the coding
      sequence for the C-terminal 59 amino acids of LLO were fused in frame to the 3'
      end of the codon-optimized gene for gp140. All plasmid vectors produced high
      levels of protein expression, and the gp140-LLO chimeric protein was cleaved and
      secreted as efficiently as gp140. Analysis of humoral immune responses by ELISA
      showed that the chimeric gp140-LLO construct induced higher antibody responses
      than the gp140 construct in immunized mice, more notably in the IgG2a antibody
      subtype. Intracellular cytokine staining and flow cytometry analysis showed that
      the gp140-LLO construct induced significantly higher levels of cytotoxic T
      lymphocyte immune responses against the HIV 89.6 Env protein than those observed
      with the gp140 construct. Our results thus demonstrate that the C-terminal
      segment of LLO can be effectively employed to enhance both cellular and humoral
      immune responses against the HIV89.6 Env antigen in the context of a DNA vaccine.

PMID- 12804000
TI  - Covert vertical transmission of feline immunodeficiency virus.
AB  - Covert vertical transmission of feline immunodeficiency virus (FIV), the feline
      counterpart of human immunodeficiency virus type 1 (HIV-1), was identified in
      kittens born to FIV-infected cats. DNA PCR detected FIV gag and env sequences in
      tissues from kittens nonviable at birth, and in viable kittens monitored
      postnatally and necropsied at either 11 weeks or 1 year of age. Although FIV DNA
      was detected in initial blood samples from all 16 viable kittens, viral DNA
      became increasingly difficult to detect over time and infectious virus could
      rarely be demonstrated. Only maternal FIV antibody was detected in kitten plasma
      during the entire postnatal observation period, and kittens remained healthy,
      with normal CD4:CD8 T cell ratios at >14 months of age. Thus, mother-to-offspring
      FIV exposure, occurring in utero and postnatally, can result in covert infection
      in kittens with virus sequestered and contained in tissue sites. These findings
      appear directly relevant to suspected transient HIV infections and reports of HIV
      specific cellular immune responses in highly exposed seronegative adults and
      uninfected infants born to HIV-positive women.

PMID- 12804001
TI  - HIV type 1 DNA development during long-term supervised therapy interruption.
AB  - We studied the pattern of HIV-1 DNA development and the association to other HIV
      related factors during long-term supervised therapy interruption (LT-STI).
      Fifteen patients were treated with long-time protease inhibitor-based
      antiretroviral therapy (PI-ART). They had HIV-1 RNA at <50 copies/ml over 33.4
      (SD 9.5) months and CD4(+) cell counts of 875 (SD 415) x 10(6)/liter. A real-time
      polymerase chain reaction, amplifying fragments of the HIV-1 pol gene and the
      human albumin gene simultaneously, was used to quantify HIV-1 DNA molecules in
      CD4(+) cells. The quantity of HIV-1 DNA in CD4(+) cells increased during LT-STI
      in all 15 patients, with an average doubling time of 2 months. Tentatively, three
      patterns were observed: rapid initial increase with subsequent stabilizing
      levels, rapid continuous increase, and slow increase. The HIV-1 DNA slope was
      positively related to the HIV-1 RNA maximum and steady state level and the
      baseline HIV-1 DNA value. It was inversely related to the decrease in CD4(+)
      cells both before the start of PI-ART and during the LT-STI. To conclude, HIV-1
      DNA persists in infected CD4(+) cells despite long-term effective PI-ART and will
      increase after therapy interruption. The most important clinical predictor of
      long-term STI failure was the rapid CD4(+) cell decline before PI-ART. In
      patients with a steep pre-PI-ART slope it may be prudent to continue treatment
      and not initiate therapy interruption.

PMID- 12804002
TI  - Simian immunodeficiency virus infection of CD4+CD8+ T cells in a macaque with an
      unusually high peripheral CD4+CD8+ T lymphocyte count.
AB  - We assessed the possible role in vivo CD4(+) CD8(+) T cells as a viral reservoir
      for simian immunodeficiency virus (SIV), in a macaque with 50% CD4(+) CD8(+) T
      cells in peripheral blood. During primary infection (day 14) of this rhesus
      macaque with the pathogenic SIVmac251 strain, proviruses were detected at similar
      frequencies in CD4(+) CD8(+) T cells (1/10) and CD4(+) T cells (1/10) and at a
      lower frequency in CD8(+) T cells (1/800). On day 235, no viral DNA was detected
      in CD8(+) cells, despite the persistent high viral load, indicating that CD8(+)
      cells do not constitute a reservoir during the chronic phase of SIV infection.
      Infection induced early lymphopenia of CD4(+), CD4(+) CD8(+), and CD8(+) cells;
      only the CD8(+) cell population returned to initial levels and expanded further.
      We found that CD4(+) CD8(+) T cells expressed the costimulatory CD28 molecule
      less and were more prone to die in vitro after phytohemagglutinin/interleukin 2
      stimulation than were CD4(+) T cells. Taken together, massive death of CD4(+)
      CD8(+) T cells during acute stages of SIV infection may explain why CD8(+) T
      cells did not represent a major reservoir for SIV at the onset of infection.

PMID- 12804003
TI  - Tropism-restricted neutralization by secretory IgA from parotid saliva of HIV
      type 1-infected individuals.
AB  - In this study we examined secretory IgA, isolated from the parotid saliva of 10
      HIV-1-infected subjects, for its ability to influence HIV-1 infection of
      peripheral blood mononuclear cells with two R5 and two X4 primary isolates.
      Salivary IgA from four subjects was found to inhibit both R5 viruses but not the
      X4 viruses. In another subject, salivary IgA inhibited both X4 viruses but not
      the R5 viruses. The specificity of these antibodies seemed to be directed
      against, but not restricted to, gp160 and gp120. Compared with subjects whose
      salivary IgA did not inhibit HIV-1 infection, subjects who displayed neutralizing
      activity were in relatively early stages of disease and had CD4(+) T cell counts
      greater than 200 cells/microl. Our data indicate the presence of tropism-specific
      (more frequently R5-specific) neutralizing antibodies in HIV-1-infected subjects.
      Because mucosal transmission of HIV-1 occurs exclusively in R5 viruses, and X4
      viruses often emerge in established infection and account for viral persistence
      later in disease, our data suggest a potential role for secretory IgA in
      preventing viral transmission, but a less likely effect on chronic infection.

PMID- 12804004
TI  - Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear
      cells from HIV-seropositive individuals is associated with interleukin 12
      receptor beta 2 upregulation.
AB  - Interleukin 12 (IL-12) production is believed to be impaired in individuals with
      HIV infection and this impairment manifests early in disease, when the CD4(+)
      cell counts are within normal values. The reduced antigen-specific and mitogen
      stimulated T cell-proliferative responses that occur in HIV infection can be
      corrected by the addition of recombinant human interleukin 12 (rhIL-12). As the
      IL-12 receptor (IL-12R) is central to the IL-12 signaling pathway, we examined
      whether the augmentation of antigen-specific proliferation of HIV(+) peripheral
      blood mononuclear cells (PBMCs) related to altered IL-12R expression. rhIL-12
      augmented antigen-specific proliferation of HIV(+) PBMCs but not of HIV(-) PBMCs.
      Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of
      these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell
      surface as detected by flow cytometry. However, examination of mRNA showed that
      both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs
      when compared with HIV(-) PBMCs. After mitogen activation there was an increase
      in IL-12R beta 1 expression on the cell surface of HIV(+) and HIV(-) PBMCs and
      this level was not altered by coculture with rhIL-12 or interferon gamma (IFN
      gamma). However, coculture of phytohemagglutinin (PHA)-activated HIV(+) or HIV(-)
      PBMCs with rhIL-12 (but not IFN-gamma) increased IL-12R beta 2 expression on the
      cell surface of both populations. Examination at the message level showed a
      correction of IL-12R beta 1 to normal levels with activation that was further
      enhanced by rhIL-12 coculture for both the HIV(+) and HIV(-) PBMCs. However,
      although the level of IL-12R beta 2 for the HIV(+) PBMCs was normalized by PHA,
      rhIL-12 caused a further augmentation. This information provides a strong link
      between IL-12R upregulation, and the significant improvement in antigen-specific
      HIV-proliferative responses seen with the addition of rhIL-12. It also reveals
      that the dysfunction in IL-12R expression seen in cells from HIV(+) patients
      occurs at the transcriptional level. In addition, we provide further evidence
      that IL-12R beta 1 and IL-12R beta 2 regulation in human PBMCs is independent of
      IFN-gamma.

PMID- 12804005
TI  - Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)
      infected Thai patients with different rates of disease progression.
AB  - Identification of immune correlates associated with disease progression will
      provide information for HIV-1 vaccine design in countries such as Thailand, where
      the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study,
      plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype
      E-infected Thai patients with different rates of disease progression, based on
      CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower
      progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated
      with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In
      progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and
      gp41 Ab did not change significantly in either group. Both CD4-binding site
      (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody
      (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary
      isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p <
      0.001). Increased NAb over time was observed more frequently in SPs as compared
      with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross
      clade antibody-dependent cellular cytotoxicity was demonstrated in both groups.
      These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a
      predictive marker of disease progression, as described for subtype B.
      Furthermore, in subtype E-infected patients, slower progressors retain the immune
      competence to develop new antibody responses to Env over time; these evolving
      responses may contribute to prolonged survival during HIV-1 disease progression.

PMID- 12804006
TI  - The expression of P-glycoprotein and cellular kinases is modulated at the
      transcriptional level by infection and highly active antiretroviral therapy in a
      primate model of AIDS.
AB  - The beneficial effects of highly active antiretroviral therapy (HAART) in HIV
      infected patients may be limited by inadequate compliance and viral resistance,
      but also by host cell factors, such as P-glycoprotein (P-gp) and intracellular
      kinases involved in the phosphorylation of nucleoside reverse transcriptase
      inhibitors. We investigated the effects of infection and HAART (zidovudine [AZT],
      lamivudine [3TC], and indinavir [IDV] on the expression of P-gp and cell kinases
      involved in the phosphorylation of AZT and 3TC in SHIV89.6P-infected cynomolgus
      macaques. Under unstimulated conditions, we observed a decrease in P-gp mRNA
      levels in the peripheral blood and lymph node mononuclear cells of infected
      macaques, which was accentuated by HAART. SHIV infection also resulted in the
      overexpression of thymidine kinase mRNA, which was abolished by HAART. In
      conclusion, retroviral infection and HAART modulate in vivo at the
      transcriptional level the expression of host cell factors that may affect the
      efficacy of HAART.

PMID- 12804007
TI  - Peptide from Tat basic domain shows striking similarity to a region of human T
      cell transcription factor 1.

PMID- 12804009
TI  - An imbalance in antioxidant defense affects cellular function: the
      pathophysiological consequences of a reduction in antioxidant defense in the
      glutathione peroxidase-1 (Gpx1) knockout mouse.
AB  - Aerobic cells are subjected to damaging reactive oxygen species (ROS) as a
      consequence of oxidative metabolism and/or exposure to environmental toxins.
      Antioxidants limit this damage, yet peroxidative events occur when oxidant stress
      increases. This arises due to increased radical formation or decreased
      antioxidative defenses. The two-step enzymatic antioxidant pathway limits damage
      to important biomolecules by neutralising superoxides to water. However, an
      imbalance in this pathway (increased first-step antioxidants relative to second
      step antioxidants) has been proposed as etiological in numerous pathologies. This
      review presents evidence that a shift in favor of hydrogen peroxide and/or lipid
      peroxides has pathophysiological consequences. The involvement of antioxidant
      genes in the regulation of redox status, and ultimately cellular homeostasis, is
      explored in murine transgenic and knockout models. The investigations of Sod1
      transgenic cell-lines and mice, as well as Gpx1 knockout mice (both models favor
      H(2)O(2) accumulation), are presented. Although in most instances accumulation of
      H(2)O(2) affects cellular function and leads to exacerbated pathology, this is
      not always the case. This review highlights those instances where, for example,
      increased Sod1 levels are beneficial, and indicates a role for superoxide
      radicals in pathogenesis. Studies of Gpx1 knockout mice (an important second-step
      antioxidant) lead us to conclude that Gpx1 functions as the primary protection
      against acute oxidative stress, particularly in neuropathological situations such
      as stroke and cold-induced head trauma, where high levels of ROS occur during
      reperfusion or in response to injury. In summary, these studies clearly highlight
      the importance of limiting ROS-induced cellular damage by maintaining a balanced
      enzymatic antioxidant pathway.

PMID- 12804010
TI  - Inhibition of protein hydroperoxide formation by protein thiols.
AB  - Studies on plasma and cells exposed to hydroxyl and peroxyl radicals have
      indicated that there are few inhibitors of protein hydroperoxide formation. We
      have, however, observed a small variable lag period during bovine serum albumin
      (BSA) oxidation by 2-2' azo-bis-(2-methyl-propionamidine) HCl (AAPH) generated
      peroxyl radicals, where no protein hydroperoxide was formed. The addition of free
      cysteine to BSA during AAPH oxidation also produced a lag phase suggesting
      protein thiols could inhibit protein hydroperoxide formation. The selective
      reduction of thiols on BSA by beta-mercaptoethanol treatment caused the
      appearance of a lag period where no protein hydroperoxide was formed during the
      AAPH mediated oxidation. Increasing free thiol concentration on the BSA increased
      the lag period. Protein hydroperoxide formation began when the protein thiol
      concentration dropped below one thiol per BSA molecule. It is unlikely that the
      lag period is due to gross structural alteration of the reduced protein since
      blocking the free thiols with N-ethyl maleimide eliminated the lag in protein
      hydroperoxide formation. Protein thiols were found to be ineffective in
      inhibiting hydroxyl radical-mediated protein hydroperoxide formation during X-ray
      radiolysis. Evidence is given for protein thiol oxidation occurring via a free
      radical mediated chain reaction with both free cysteine and protein bound thiol.
      The data suggest that reduced protein thiol groups can inhibit protein
      hydroperoxide formation by scavenging peroxyl radicals.

PMID- 12804011
TI  - Identification of multiple transcripts for antioxidant protein 2 (Aop2):
      differential regulation by oxidative stress and growth factors.
AB  - Antioxidant protein 2 is a unique member of the thiol-specific antioxidant family
      of proteins known to reduce reactive oxygen species in the presence of thiol
      containing electron donors. It is also a candidate atherosclerosis susceptibility
      gene in mice. In the present study, we sought to characterize the transcripts of
      this gene, and determine which, if any, are regulated by conditions associated
      with oxidative stress. We have identified multiple Aop2 transcripts by Northern
      blot, each exhibiting a unique tissue distribution. These include the previously
      reported 1.47 kb major transcript, two alternative Aop2 transcripts found
      exclusively in liver, and a testis-specific transcript believed to be the highly
      related intronless gene Aop2-rs1. Treatment of a murine hepatocyte cell line with
      glucose oxidase led to the specific and transient induction of the 1.47 kb
      transcript, while the 3.1 kb transcript was regulated by serum deprivation and re
      stimulation with either keratinocyte growth factor or serum in a time-dependent
      manner. Since these ROS-inducing stimuli involve different mechanisms of action
      and cellular responses, our data suggest that alternative Aop2 transcripts may
      play distinct roles in different oxidative stress responses, and possibly in
      atherosclerosis.

PMID- 12804012
TI  - Protection of endogenous beta-carotene in LDL oxidized by oxygen free radicals in
      the presence of supraphysiological concentrations of melatonin.
AB  - This study was designed to evaluate the effect of high concentrations of
      melatonin on the peroxidation of human low density lipoproteins (LDLs) initiated
      by O(2)(*-) and ethanol-derived peroxyl radicals (RO(2)(*)) from water gamma
      radiolysis in the presence of ethanol. LDL (3 g/l; total LDL concentration) was
      oxidized in the absence of melatonin or in its presence at three concentrations
      (50 x 10(-6), 100 x 10(-6) or 250 x 10(-6) mol/l) in ethanol. Radiolytic yields
      (i.e. number of mole consumed or produced per Joule) of the markers of lipid
      peroxidation were determined (i.e. decrease in the endogenous antioxidants alpha
      tocopherol and beta-carotene, formation of conjugated dienes and of
      thiobarbituric acid-reactive substances [TBARS]). Melatonin decreased the yields
      of lipid peroxidation products and delayed the onset of the propagation phase for
      conjugated dienes and TBARS in a concentration-dependent manner. Nevertheless,
      melatonin did not protect endogenous alpha-tocopherol against peroxyl-induced
      oxidation (probably due to a lower scavenging capacity than that of alpha
      tocopherol towards peroxyl radicals), but delayed the consumption of LDL
      endogenous beta-carotene and decreased its rate of disappearance. The effect of
      melatonin seemed to be the highest for a melatonin concentration of 250 x 10(-6)
      mol/l.

PMID- 12804014
TI  - Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the
      macrophage-synthesised pterin, 7,8-dihydroneopterin.
AB  - Human macrophages release the pterin, 7,8-dihydroneopterin when exposed to the
      immune stimulant gamma-interferon (IFN-gamma). Previous in vitro studies have
      shown 7,8-dihydroneopterin is a potent antioxidant, which inhibits copper- and
      peroxyl-radical mediated low-density lipoprotein (LDL) oxidation. Using THP-1
      cells, a human derived monocyte-like cell line, we have found that low micromolar
      concentrations of 7,8-dihydroneopterin inhibit cell mediated oxidation of LDL, as
      measured by electrophoretic mobility, alpha-tocopherol loss, and lipid oxidation.
      Stimulation of the THP-1 cells with IFN-gamma caused a significant reduction in
      the cells' ability to oxidise LDL. The extracellular pterin concentration
      increased from 0 to 16 nM with IFN-gamma stimulation, while the intracellular
      concentration increased from 0.21 to 1.69 nmol/mg cell protein.

PMID- 12804013
TI  - Inhibition of benzoyl peroxide and ultraviolet-B radiation induced oxidative
      stress and tumor promotion markers by cycloartenol in murine skin.
AB  - The chemopreventive potential of cycloartenol on benzoyl peroxide and UVB
      radiation-induced cutaneous tumor promotion markers and oxidative stress in
      murine skin is assessed. Benzoyl peroxide treatment (20 mg/animal/0.2 ml acetone)
      and UVB radiation (0.420 J/m(2)/s) caused a decrease in the activities of
      cutaneous antioxidant enzymes namely, catalase, glutathione peroxidase,
      glutathione reductase, glucose-6-phosphate dehydrogenase, phase II metabolizing
      enzyme such as glutathione-S-transferase and quinone reductase and depletion in
      the level of cutaneous glutathione. There was also enhancement in cutaneous
      microsomal lipid peroxidation, xanthine oxidase activity, [(14)C]-ornithine
      decarboxylase activity and [(3)H]-thymidine incorporation into cutaneous DNA.
      Cycloartenol was topically applied prior to the application of benzoyl peroxide
      at dose levels of 0.2 mg and 0.4 mg/kg body weight in acetone, which resulted in
      significant inhibition of epidermal ornithine decarboxylase activity and DNA
      synthesis (P < 0.001). There was also significant reduction of lipid peroxidation
      and xanthine oxidase activity (P < 0.001). In addition, the depleted levels of
      glutathione, inhibited activities of antioxidant and phase II metabolizing
      enzymes, were also recovered to a significant level (P < 0.001). The data
      indicate that cycloartenol is an effective chemopreventive agent in skin
      carcinogenesis.

PMID- 12804015
TI  - Efficacy of soyfoods and soybean isoflavone supplements for alleviating
      menopausal symptoms is positively related to initial hot flush frequency.
AB  - Soy has received attention as an alternative to conventional hormone replacement
      therapy (HRT) largely because it is a unique dietary source of isoflavones.
      Isoflavones are diphenolic compounds that have both hormonal and nonhormonal
      properties and are considered to be selective estrogen receptor modulators. The
      estrogen-like effects of isoflavones in combination with the low reported
      frequency of hot flushes in Japan has prompted investigation of the effect of soy
      on menopausal symptoms. The purpose of this review is to evaluate the efficacy of
      soyfoods and isoflavone supplements for the alleviation of hot flushes. Nineteen
      trials (13 using a parallel design) involving more than 1,700 women were
      identified. Six trials were excluded from analysis: two that involved breast
      cancer patients, two that reported data on severity but not hot flush frequency,
      one that was not blinded, and one that did not include a control group. Based on
      a simple regression analysis of the remaining data set (13 trials), there was a
      statistically significant relationship (P =.01) between initial hot flush
      frequency and treatment efficacy. Initial hot flush frequency explained about 46%
      of the treatment effects, and hot flush frequency decreased by about 5% (above
      placebo or control effects) for every additional initial hot flush per day in
      women whose initial hot flush frequency was five or more per day. Although
      conclusions based on this analysis should be considered tentative, the available
      data justify the recommendation that patients with frequent hot flushes consider
      trying soyfoods or isoflavone supplements for the alleviation of their symptoms.

PMID- 12804016
TI  - Effect of D-003 on isoproterenol-induced myocardial necrosis in rats.
AB  - D-003 is a mixture of high-molecular-weight aliphatic primary acids purified from
      sugar cane wax with antiplatelet and cholesterol-lowering effects. Cardiac
      lesions induced by isoproterenol (ISO) are characterized by myocardial necrosis
      and exudative infiltration. The objective of this study was to determine whether
      D-003 shows protective effects against ISO-induced myocardial necrosis in rats.
      Effects of orally administered single doses of D-003 (25-400 mg/kg) and
      acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5-200
      mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were
      investigated. D-003 administered as single doses dose-dependently decreased
      necrosis area, percent of infarct area, and the presence of polymorphonuclear
      cells (PMNs) in myocardial tissue, but only the reductions induced by 200 and 400
      mg/kg were significant. Oral acute treatment with ASA also decreased necrosis
      area and percent of infarct area, but the occurrence of PMNs was unchanged. D-003
      administered repeatedly for 10 days also decreased all myocardial necrosis
      indicators in a dose-dependent manner, with results effective from 25 mg/kg to
      the highest dose tested, indicating that the repeated dose scheme was more
      effective to prevent the damage. It is concluded that D-003 shows a protective
      effect on the myocardial necrosis induced by ISO in rats.

PMID- 12804017
TI  - Reduction of cancer risk by consumption of selenium-enriched plants: enrichment
      of broccoli with selenium increases the anticarcinogenic properties of broccoli.
AB  - Plant-based diets and phytochemicals present in plants are associated with
      decreased risk of cancer. Brassica species, and broccoli in particular, are
      associated with reduced risk of several important cancers. Selenium (Se) is an
      essential nutrient that is covalently bound in a number of different chemical
      forms found in plants. Broccoli accumulates Se many-fold beyond the concentration
      of Se in the soil, and the chemical form of Se in broccoli is similar to the
      chemical form in high-Se garlic, a food with unique chemoprotective properties.
      Se from broccoli grown to accumulate more than 500 micro g Se/g did not
      accumulate in rat tissues or increase glutathione peroxidase enzyme activity to
      the same extent as Se salts or seleno-amino acids. Se from high-Se broccoli
      decreased the incidence of aberrant crypts in rats with chemically induced colon
      cancer by more than 50%, compared with controls. Se from high-Se broccoli also
      decreased the incidence of mammary tumors in rats treated with 7,12
      dimethylbenz(a)anthracene (DMBA) and tumor number and volume in APC(min) mice.
      These results suggest that development of methods to increase the natural
      accumulation of Se in broccoli may greatly enhance its health-promoting
      properties.

PMID- 12804018
TI  - Use of vitamins, minerals, and other dietary supplements by 17- and 18-year-old
      students in Korea.
AB  - Various types of dietary supplements (DS) are popularly taken by young
      individuals. We surveyed 1,190 Korean senior high school third grade students for
      their DS use, motivational factors for this use, and potential dietary
      consequences of vitamin/mineral supplement (VMS) use. The use prevalence of DS
      including VMS, tonic medicines, manufactured health food supplements, cordial
      food supplements, and drink rehabilitators-was 54%. VMS were taken most
      frequently, followed by tonic medicines and manufactured health food supplements.
      VMS use was highest in individuals who had a significant concern for their
      overall health and in those from families with a high socioeconomic level and
      with parental use of DS. Total daily study time of DS users was only slightly
      longer than that of nonusers. The VMS most frequently used were vitamin C and
      multivitamins. More than 46% of other DS users, and 58% of VMS users, had
      increased their intake of supplements during third grade relative to the previous
      year. VMS users had a more positive view of the potential health benefit of VMS
      than did nonusers. Vitamin and mineral intakes from VMS occurred over a wide
      range, with mean intakes typically exceeding the Korean and Canadian-U.S.
      Recommended Dietary Allowances. For a significant number of individuals, intakes
      of vitamin A, niacin, folic acid, vitamin C, calcium, iron, and zinc exceeded the
      Tolerable Upper Intake Levels. Given the widespread use of DS by older teenagers,
      the contribution of these supplements to their overall health and well-being is a
      subject that clearly merits additional study.

PMID- 12804019
TI  - Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate
      metabolic enzymes in alloxan-induced diabetic rats.
AB  - The effects of Gymnema montanum, an endangered plant used in the ancient period
      of India, on blood glucose, plasma insulin, and carbohydrate metabolic enzymes
      were studied in alloxan diabetic rats. Administration of alcoholic extract of G.
      montanum leaves (50, 100, 200 mg/kg body weight) to alloxan diabetic rats for 3
      weeks reduced the blood glucose level. Administration of G. montanum leaf extract
      (GLEt) at 200 mg/kg body weight significantly decreased the blood glucose levels
      and significantly increased the plasma insulin levels. This clearly shows the
      antidiabetic efficacy of GLEt, which was better than that of glibenclamide.

PMID- 12804020
TI  - Safety of an astaxanthin-rich Haematococcus pluvialis algal extract: a randomized
      clinical trial.
AB  - A growing body of scientific literature indicates that astaxanthin is a more
      powerful antioxidant than other carotenoids and vitamin E and may confer numerous
      health benefits. The purpose of this investigation was to conduct a human safety
      study with a Haematococcus pluvialis algal extract with high levels of
      astaxanthin. Thirty-five healthy adults age 35-69 years were enrolled in a
      randomized, double-blind, placebo-controlled trial of 8 weeks' duration. All
      participants took three gelcaps per day, one at each meal. Nineteen participants
      received gelcaps with an algal extract in safflower oil, containing 2 mg of
      astaxanthin each (treatment); 16 participants received gelcaps containing
      safflower oil only (placebo). Blood pressure and blood chemistry tests, including
      a comprehensive metabolic panel and cell blood count, were conducted at the
      beginning of the trial and after 4 and 8 weeks of supplementation. No significant
      differences were detected between the treatment and the placebo groups after 8
      weeks of supplementation with the algal extract in the parameters analyzed,
      except for serum calcium, total protein, and eosinophils (P <.01). Although the
      differences in these three parameters were statistically significant, they were
      very small and are of no clinical importance. These results reveal that 6 mg of
      astaxanthin per day from a H. pluvialis algal extract can be safely consumed by
      healthy adults.

PMID- 12804021
TI  - Antibacterial activity of berry fruits used for culinary purposes.
AB  - Increasing interest in the health benefits of various culinary berries has led to
      investigation of their antibacterial activity. Commercial raspberry,
      blackcurrant, cranberry, and blackberry cordials (100% fruit) as well as fresh
      berries were assessed for their ability to inhibit the growth of various bacteria
      and the yeast Candida albicans. Three of the six raspberry cordials and the
      blackcurrant cordial inhibited all 12 bacteria and C. albicans at dilutions of
      1:5. Bacteria showed varying susceptibilities to the remaining cordials. All
      cordials inhibited the growth of Mycobacterium phlei. Of the fresh berries,
      mulberries and boysenberries did not inhibit any bacteria, and the remaining
      berries inhibited the growth of varying numbers of bacteria. There was no
      correlation between gram-positive or gram-negative bacterial status and
      susceptibility to the berries. It is suggested that the antibacterial activity of
      these berries may be of benefit as a means of water purification for suspect
      water supplies or to enhance shelf life when incorporated into food products.

PMID- 12804022
TI  - Effect of sumach (Rhus coriaria L.) extracts on the oxidative stability of peanut
      oil.
AB  - The antioxidant activities of sumach (Rhus coriaria L.) extracts and butylated
      hydroxyanisole (BHA) at various concentrations were tested in natural peanut oil
      stored at 65 degrees C for 35 days. The concentrations (weight/volume) of
      extracts added into oil were 1.0%, 3.0%, and 5.0%, and those of BHA were 0.1%,
      0.3%, and 0.5%. Antioxidant effect was determined by the measurement of peroxide
      value. After 7 days of storage, BHA and extracts of sumach were active in varying
      degrees against autoxidation of peanut oil, compared with the control test (P
      <.01). The sumach extracts generally inhibited the formation of hydroperoxide, as
      did BHA. After 28 days of storage, antioxidant effects of extracts were
      significantly decreased when compared with BHA. The decrease in the antioxidant
      activity of extracts might have resulted from the decrease of polyphenolic
      constituents. The results showed that high concentrations can enhance the potency
      of the antioxidant effect of sumach extract.

PMID- 12804023
TI  - Avatars in clinical psychology: a framework for the clinical use of virtual
      humans.
AB  - Early applications of virtual reality (VR) technology in psychological
      assessment, treatment, and research have yielded promising results. In
      particular, an increasing number of studies analyze the unique features of the
      experience made by patients during their exposure to virtual environments.
      However, the majority of these studies explore how patients navigate in the
      virtual spaces and interact with virtual objects. Only a few of them investigate
      the features of inhabited virtual environments, where real people and autonomous
      virtual humans are able to interact and to cooperate. In particular, there is a
      lack of discussion of the role that such autonomous virtual humans could have in
      VR-aided psychotherapy. The main goal of this paper is to identify a framework
      for future research in this area. Three levels of analysis are identified. The
      purpose of the first two levels is the identification of the key "physical"
      features (e.g., appearance, structure) and "internal" characteristics (e.g.,
      behavior, degree of autonomy, perceptual capabilities) needed by an effective
      simulation. The third level is concerned with the evaluation of the interaction
      characteristics required for a successful relationship between the patient and
      the virtual human.

PMID- 12804024
TI  - The illusion of presence in immersive virtual reality during an fMRI brain scan.
AB  - The essence of immersive virtual reality (VR) is the illusion it gives users that
      they are inside the computer-generated virtual environment. This unusually strong
      illusion is theorized to contribute to the successful pain reduction observed in
      burn patients who go into VR during woundcare (www.vrpain.com) and to successful
      VR exposure therapy for phobias and post-traumatic stress disorder (PTSD). The
      present study demonstrated for the first time that subjects could experience a
      strong illusion of presence during an fMRI despite the constraints of the fMRI
      magnet bore (i.e., immobilized head and loud ambient noise).

PMID- 12804025
TI  - The relationship between internet activities and depressive symptoms in a sample
      of college freshmen.
AB  - An Internet survey of college freshmen at a mid-Atlantic mid-sized university was
      conducted during the spring of 2002 to determine the impact of Internet
      activities on social support and well-being. Results obtained from the survey
      allow examination of the impact of amount of time performing different types of
      Internet activities on depressive symptoms, as measured by the Iowa version of
      the Center for Epidemiologic Studies Depression Scale (CES-D) via a semi
      elasticity ordinary least squares regression model. Results indicate that
      increased e-mail and chat room/instant messaging (IM) hours are associated with
      decreased depressive symptoms, while increased Internet hours for shopping,
      playing games, or research is associated with increased depressive symptoms. The
      implications of these results for institutions of higher education, and Internet
      and health researchers are discussed.

PMID- 12804026
TI  - Internet over-users' psychological profiles: a behavior sampling analysis on
      internet addiction.
AB  - What kinds of psychological features do people have when they are overly involved
      in usage of the internet? Internet users in Korea were investigated in terms of
      internet over-use and related psychological profiles by the level of internet
      use. We used a modified Young's Internet Addiction Scale, and 13,588 users (7,878
      males, 5,710 females), out of 20 million from a major portal site in Korea,
      participated in this study. Among the sample, 3.5% had been diagnosed as internet
      addicts (IA), while 18.4% of them were classified as possible internet addicts
      (PA). The Internet Addiction Scale showed a strong relationship with
      dysfunctional social behaviors. More IA tried to escape from reality than PA and
      Non-addicts (NA). When they got stressed out by work or were just depressed, IA
      showed a high tendency to access the internet. The IA group also reported the
      highest degree of loneliness, depressed mood, and compulsivity compared to the
      other groups. The IA group seemed to be more vulnerable to interpersonal dangers
      than others, showing an unusually close feeling for strangers. Further study is
      needed to investigate the direct relationship between psychological well-being
      and internet dependency.

PMID- 12804027
TI  - How does schema theory apply to real versus virtual memories?
AB  - Schemas are cognitive frameworks that guide memory, aide in the interpretation of
      events, and influence how we retrieve stored memories. The purpose of this study
      was to explore how schemas operate in a well-known environment and to examine
      whether or not schemas operate differently in real versus virtual environments.
      Twenty-four undergraduate students from a small liberal arts college in the
      northeast participated for course credit. Two identical offices (a real office
      and a virtual office) were created and filled with eight consistent and eight
      inconsistent items. Each participant explored either the real office or the
      virtual office for 20 seconds without any knowledge that their memory would be
      tested. After leaving the office, participants completed a recognition task and a
      short demographic questionnaire. Overall sensitivity and higher confidence in
      recognition memory scores was found for inconsistent compared to consistent
      items. Greater support for the consistency effect was observed in this study and
      interpreted in terms of the dynamic memory model and the schema-plus-correction
      model. The results also demonstrate that virtual reality paradigms may produce
      similar outcomes compared to the real world in terms of some memory processes,
      but additional design factors must be considered if the researcher's goal is to
      create equivalent paradigms.

PMID- 12804028
TI  - The process of sharing social support in cyberspace.
AB  - Mutual support is an interactional communication process. Taking an interactional
      approach to support requires group participants be viewed not only as targets and
      recipients but also as sources and providers of various types of support. An
      analysis was performed on the interactions of a group listserve and model of
      online interactional support. The aim was to explore the communication process
      children follow. The analysis revealed self-disclosure was used in the support
      group in three distinct ways. Its function for the support recipient is to
      initiate a transactional relationship with another member for the purpose of
      attracting social support through the open expression of concerns and
      frustrations. It is then used by the support provider to demonstrate that coping
      is possible for the recipient through the reciprocal self-disclosure of similar
      concerns and situations with which the member has successfully dealt. The third
      use of self-disclosure was to share reciprocal social companionship
      relationships.

PMID- 12804029
TI  - Flow-based model of computer hackers' motivation.
AB  - Hackers' psychology, widely discussed in the media, is almost entirely unexplored
      by psychologists. In this study, hackers' motivation is investigated, using the
      flow paradigm. Flow is likely to motivate hackers, according to views expressed
      by researchers and by hackers themselves. Taken as granted that hackers
      experience flow, it was hypothesized that flow increases with the increase of
      hackers' competence in IT use. Self-selected subjects were recruited on
      specialized web sources; 457 hackers filled out a web questionnaire. Competence
      in IT use, specific flow experience, and demographic data were questioned. An on
      line research was administered within the Russian-speaking community (though one
      third of Ss are non-residents of Russian Federation); since hacking seems to be
      international, the belief is expressed that the results are universal. The
      hypothesis is not confirmed: flow motivation characterizes the least and the most
      competent hackers, and the members of an intermediate group, that is, averagely
      competent Ss report the "flow crisis"-no (or less) flow experience. Two differing
      strategies of task choice were self-reported by Ss: a step-by-step increase of
      the difficulty of choices leads to a match of challenges and skills (and to
      preserving the flow experience); putting choices irrespective of the likelihood
      of solution leads to a "flow crisis." The findings give productive hints on
      processes of hackers' motivational development. The flow-based model of computer
      hackers' motivation was developed. It combines both empirically confirmed and
      theoretically possible ways of hackers' "professional" growth.

PMID- 12804030
TI  - The subjective sense of presence, emotion recognition, and experienced emotions
      in auditory virtual environments.
AB  - Realistic aural rendering of events in mediated environments is becoming an
      increasingly important aspect in many multi-modal applications. In a between
      group experiment with 45 participants, it was studied how ratings of presence (a
      sense of being in the mediated environment), emotional reactions to the auditory
      environment, and emotion recognition vary as a function of number of audio
      channels (mono, stereo, and six-channel reproduction). The results showed that
      stereo and six-channel reproduction resulted in significantly stronger changes in
      emotional reactions than the mono condition. Further, six-channel reproduction
      received the highest ratings of presence and emotional realism. Taken together,
      the result suggested that both emotional reactions and ratings of presence
      increase with spatialized sound. Further, emotional reactions and presence were
      highly correlated. The results are discussed in relation to theories of mediated
      presence and emotional reactions in an attempt to further delineate the concept
      of presence.

PMID- 12804031
TI  - Fund-raising on the web: the effect of an electronic door-in-the-face technique
      on compliance to a request.
AB  - In an attempt to test the door-in-the-face (DITF) technique in a computer
      mediated context, 1,607 men and women taken at random in various e-mail lists
      were solicited to visit a web site for the profit of a humanitarian organization.
      In DITF condition, subjects were first solicited by an exaggerated request and,
      after refusing, were solicited for a small donation. In control condition the
      donation solicitation was formulated directly. In all the cases, the request was
      manipulated by the order of the successive HTML pages of the site. Results show
      that the DITF procedure increase compliance to the last request. The theoretical
      implication of the effect of this technique in a computer-communication context
      is discussed.

PMID- 12804032
TI  - Child of the internet: perceptions of creativity in e-identities.

PMID- 12804033
TI  - Factors influencing clicking of banner ads on the WWW.
AB  - This paper explores various factors influencing the clicking of banner ads on the
      WWW. The study indicates that several important variables affect the clicking of
      banner ads: (1) level of product involvement, (2) congruency between the content
      of a vehicle and the product category of a banner ad, (3) attitude toward the
      vehicle, and (4) overall attitude toward web advertising. For methodology, this
      study employed a between-group experimental design and measured real click
      through rates with the aid of an online data collection technology called
      FileMaker Pro. Results of logistic regressions show that people are more likely
      to click banner ads if they are highly involved with products, perceive high
      synergy between web pages and ads, have a favorable attitude toward a vehicle, or
      have a favorable attitude toward web advertising in general. A total of 756
      subjects participated in this research.

PMID- 12804035
TI  - Analysis of a mitochondrial apoptotic pathway using Bid-targeted ribozymes in
      human MCF7 cells in the absence of a caspase-3-dependent pathway.
AB  - In normal cells, tumor necrosis factor-alpha (TNF-alpha) activates caspase 8 in
      both mitochondrion-dependent and mitochondrion-independent apoptotic pathways. It
      is believed that these two pathways converge, with resultant activation of
      effector caspases, such as caspase 6 and caspase 7. However, the precise
      mechanism of the activation of caspases 6 and 7 remains unknown. In this study,
      in order to focus on the mitochondrion-dependent pathway, we employed MCF7 human
      breast carcinoma cells, which do not have a functional mitochondrion-independent
      (caspase 3-dependent) pathway. We specifically targeted the transcript of Bid, a
      proapoptotic facilitator that is a substrate of caspase 8 in the mitochondrial
      pathway. In the TNF-alpha-treated MCF7 cells that expressed Bid-targeted
      ribozymes, the release of cytochrome c and the activation of caspase 9, but not
      of caspase 8, was delayed. Furthermore, the proteolysis of procaspase 7 was also
      delayed in Bid ribozyme-expressing cells. Because MCF7 cells are caspase 3
      deficient, the direct cross-talk between caspase 8 and caspase 3 does not take
      place. Therefore, it became clear for the first time that caspase 9 by itself can
      activate caspase 7 in the absence of the caspase 3-dependent pathway in TNF-alpha
      induced apoptosis by the use of specific ribozymes.

PMID- 12804036
TI  - Sequence, chemical, and structural variation of small interfering RNAs and short
      hairpin RNAs and the effect on mammalian gene silencing.
AB  - Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in
      mammalian cells and guide mRNA degradation in the process of RNA interference
      (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3
      cells, we investigated the positional variation of siRNA-mediated gene silencing.
      We find cell-type-dependent global effects and cell-type-independent positional
      effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells
      but displayed a very similar pattern of positional variation of lamin A/C
      silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA
      duplexes reduced the protein expression by at least 90%, and only 2 duplexes
      reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb
      gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand
      and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of
      the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate
      and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not
      significantly affect silencing efficiency, although cytotoxic effects were
      observed when every second phosphate of an siRNA duplex was replaced by
      phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for
      lamin A/C silencing as a function of stem length and loop composition. As long as
      the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19
      29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin
      started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly
      active.

PMID- 12804037
TI  - Delivery of antisense oligonucleotide to the cornea by iontophoresis.
AB  - We wished to evaluate the potential of iontophoresis to promote the delivery of
      antisense oligonucleotides (ODN) directed at the vascular endothelial growth
      factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence
      (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally
      administered to rat eyes, and their fate within the anterior segment was studied.
      Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats
      were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM)
      were delivered by iontophoresis (300 microA for 5 minutes) using a specially
      designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM)
      were delivered using the same applicator, but no electrical current was applied.
      In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior
      to the application of ODNs (20 microM), and iontophoresis electrical current was
      delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM)
      iontophoresis application (300 microA for 5 minutes) and were used for ODN
      integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours
      after a single ODN application and studied. Topically applied ODNs using the same
      iontophoresis applicator but without current do not penetrate the cornea and
      remain confined to the superficial epithelial layer. ODNs delivered with
      transcorneoscleral iontophoresis penetrate into all corneal layers and are also
      detected in the iris. In corneas with neovascularization, ODNs were particularly
      localized within the vascular endothelial cells of the stroma. ODNs extracted
      from eye tissues 24 hours after iontophoresis remained unaltered. The
      iontophoresis current did not cause any detectable ocular damage under these
      conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment
      of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF
      R2 may be used for the design of specific antiangiogenic strategy in diseases of
      the cornea.

PMID- 12804038
TI  - Rapid identification of antisense mRNA-expressing clones using strand-specific RT
      PCR.
AB  - Transfection of full-length antisense cDNA is used frequently to achieve stable
      downregulation of gene expression. However, screening for clones that express the
      antisense mRNA is complicated by the presence of endogenous sense mRNA. Thus,
      clones usually are screened for downregulation of the target protein by Western
      blotting, which can be time consuming. Here, we used strand-specific RT-PCR to
      identify antisense-expressing clones, which can then be screened for protein
      downregulation. This approach allows earlier identification of potentially useful
      clones and cuts down on the number of clones to be screened by Western blotting.

PMID- 12804039
TI  - Preclinical studies targeting normal and leukemic hematopoietic cells with
      Yttrium-90-labeled anti-CD45 antibody in vitro and in vivo in nude mice.
AB  - A study was undertaken to investigate the suitability of using a high affinity
      (Kd = 1.1 nM) anti-CD45 monoclonal antibody for delivering the high energy beta
      particle emitting isotope (90)Y to lymphohematopoietic target cells in vivo. The
      antibody, AHN-12, recognized the tyrosine phosphatase CD45 expressed on the
      surface of normal and malignant hematopoietic cells and studies showed that it
      reacted with both CD45-expressing normal peripheral blood cells and leukemia
      cells from patients. The antibody was readily labeled with (90)Y using the highly
      stable chelate 1B4M-DTPA and the radioimmunoconjugate was designated (90)Y-anti
      CD45. The agent selectively bound to CD45(+) B cell line Daudi, but not CD45(-)
      control cells and significantly (p = 0.007) more bound to Daudi tumors growing in
      athymic nude mice than did a control non-reactive antibody. Moreover,
      biodistribution data correlated well to an anti-Daudi effect observed against
      established tumors in nude mice. The effect was dose dependent and irreversible
      with the best results in mice receiving a single dose of 137 microCi (90)Y-anti
      CD45. These mice displayed a significantly (p < 0.0095) better anti-tumor effect
      than a control (90)Y-labeled antibody and survived over 135 days with no evidence
      of tumor. Histology studies showed no significant injury to kidney, liver, or
      small intestine even at 254 microCi, the highest dose tested. Because
      radiolabeled anti-CD45 antibody can be used to deliver radiation selectively to
      lymphohematopoietic tissue, these data indicate that this agent may be used to
      improve treatment of hematopoietic malignancies, particularly leukemia and
      lymphoma, when combined with hematopoietic stem cell transplantation in a future
      clinical trial.

PMID- 12804040
TI  - Effect of gelatins on human cancer cells in vitro.
AB  - Three types of gelatins were tested for their antiproliferative activities in
      vitro against three human tumor cell lines (K-562; erythroleukemia, HCT-15; colon
      carcinoma, AGS; gastric carcinoma) with viable cell count and tritium-thymidine
      ((3)H-TdR) uptake by those cells. Porcine skin (PS) gelatin exerted the strongest
      antiproliferative activity of all three gelatins. Bovine bone (BB) gelatin did
      not exert such an activity. PS gelatin exerted antiproliferative activity against
      K-562 cells also in a serum-free medium. The serum-free medium contains two
      growth factors, insulin and transferrin, as well as nutrients. The activity of PS
      gelatin was not interfered by addition of insulin and transferrin to the medium.
      Effect of diluting a K-562 cell-concentration on the activity of PS gelatin was
      tested. Diluting the cell concentration did not affect the activity of PS
      gelatin. Moreover, the conditioned medium in which K-562 cells had been cultured
      did not stimulate the proliferation of K-562 cells. In conclusion, PS gelatin
      suppress the proliferation of human tumor cell lines in vitro. The
      antiproliferative activity of PS gelatin might not be attributed to trapping
      growth factors or autocrine mediators.

PMID- 12804041
TI  - Effects of 13-cis-retinoic acid on chemoimmunotherapy of metastatic renal cell
      carcinoma--results of a retrospective analysis.
AB  - Chemoimmunotherapy (CIT) with interleukin-2, interferon-alpha2a, and 5
      fluorouracil is an accepted treatment option of metastatic renal cell carcinoma
      (mRCC). Because of the enhancement of the antiproliferative effects of interferon
      alpha2a, 13-cis-retinoic acid (13-CRA) might be of potential usefulness for
      immunotherapy. We have investigated the effect of 13-CRA in patients treated with
      chemoimmunotherapy. Seventy-two patients with mRCC and a Karnofsky performance
      index > or = 80% were retrospectively analyzed. Thirty-six patients received
      chemoimmunotherapy and 36 other patients were treated similarly but with addition
      of daily 60 mg 13-CRA. Response was assessed according to the UICC criteria.
      Survival was calculated by Kaplan Meier estimation and compared with the log-rank
      test. In the CIT group objective remissions occurred in 34.3% (95% CI 19.1-52.2)
      and stabilizations in 42.9% (median follow-up 16 months). In the CIT plus 13-CRA
      group, objective remissions were seen in 26.4% (95% CI 12.9-44.4) and
      stabilizations in 50% (median follow-up 17 months). One- and three-year survival
      rates were 76% and 32% in the CIT group and 82% and 37% in the CIT plus 13-CRA
      group. The combination of CIT and 13-CRA did not significantly differ in
      objective remissions and estimated survival compared with CIT. Our retrospective
      data suggest that 13-CRA does not enhance the therapeutic efficacy of CIT in mRCC
      patients with a good performance status.

PMID- 12804042
TI  - Radiation dosimetry results from a Phase II trial of ibritumomab tiuxetan
      (Zevalin) radioimmunotherapy for patients with non-Hodgkin's lymphoma and mild
      thrombocytopenia.
AB  - This was a 30-patient Phase II trial of reduced-dose (90)Y ibritumomab tiuxetan
      (Zevalin) RIT for patients with low-grade, follicular, or transformed B-cell NHL
      and mild thrombocytopenia. Patients were given an imaging dose of (111)In-labeled
      ibritumomab tiuxetan for dosimetry measurements. One week later, patients were
      administered a therapeutic dose of 0.3 mCi/kg (11 MBq/kg) (90)Y ibritumomab
      tiuxetan. Both (111)In- and (90)Y-labeled ibritumomab tiuxetan doses were
      preceded by an infusion of 250 mg/m(2) rituximab (Rituxan, MabThera) an unlabeled
      chimeric anti-CD20 antibody, to clear peripheral blood B cells and improve
      biodistribution of the radiolabeled antibody. For all 30 patients, normal organ
      and red marrow radiation absorbed doses were well below protocol-defined limits
      of 2000 cGy and 300 cGy, respectively. Median radiation absorbed doses were 48
      cGy to red marrow (range: 6.5-95 cGy), 393 cGy to liver (range: 92-1581 cGy), 522
      cGy to spleen (range: 165-1711 cGy), 162 cGy to lungs (41-295 cGy), and 14 cGy to
      kidneys (0.03-65 cGy). Though most correlative analyses were negative, certain
      analyses demonstrated a statistically significant correlation between the
      severity or duration of thrombocytopenia and pharmacokinetic or dosimetric
      parameters. These correlations were not consistent across the total patient
      population, and therefore, could not be exploited to predict hematologic
      toxicity.

PMID- 12804043
TI  - An overview of attenuation and scatter correction of planar and SPECT data for
      dosimetry studies.
AB  - A number of factors impact the accuracy of activity quantitation in planar and
      single photon emission computed tomographic (SPECT) imaging. Two important such
      factors are attenuation and scattering in the medium containing the activity. The
      first removes photons which otherwise would have been included in the images, and
      the second adds events to the images from photons which would not have otherwise
      been imaged. A number of methods have been developed to compensate for these
      biases to activity quantitation. This review will briefly introduce planar
      quantitation which is commonly used for dosimetric purposes, and then present a
      slightly more detailed overview of SPECT quantitation which is arguably more
      accurate. It will conclude by cautioning users of commercial reconstruction
      software to validate it for quantitation before using it for dosimetric purposes.

PMID- 12804044
TI  - Impact of scatter and attenuation corrections for iodine-131 two-dimensional
      quantitative imaging in patients.
AB  - This study assessed the impact of scatter and attenuation corrections on the
      estimated activity delivered to whole body and liver in five patients included in
      a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical,
      transmission images were acquired with the Transmission Attenuation Correction -
      Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed
      list mode at least four times after injection. 20% window and scatter-corrected
      images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated.
      Whole-body activity was calculated 1-h after injection (and compared with
      injected activity). Cumulated activities in whole body and liver were determined
      according to the geometric mean approach. The mean relative error made in
      estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections.
      Taking scatter into account led to underestimation, but reduced the influence of
      patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation
      correction led to a large overestimation, whether used alone (155.2+/-39.0%) or
      associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and
      TEW). Compared to the geometric mean alone, scatter correction led to a reduction
      of cumulated activities of around 45% for whole body and less than 30% for liver.
      Attenuation correction had a more marked impact, particularly for liver where
      estimated cumulated activity increased from 150 to 300%. Preliminary scatter
      correction limited the increase to 100% for DEW and 150% for TEW in liver and to
      25% for both DEW and TEW in whole body. Although this would probably be different
      at the organ level, the calculation of whole-body activity without scatter and
      attenuation correction gave the lowest biases. But from a scientific point of
      view, this cannot be a satisfactory method. Attenuation correction has a greater
      impact than scatter correction. The association of both corrections is not
      sufficient to obtain accurate absolute quantification. Other factors limit planar
      quantification with iodine-131, notably auto-absorption of sources, septal
      penetration of high-energy photons through the collimator and superimposition of
      sources.

PMID- 12804045
TI  - Calibration of a radioactive ink-based stack phantom and its applications in
      nuclear medicine.
AB  - This paper describes a stack phantom useful for imaging complex activity
      distributions. It is based on images printed with radioactive ink using a
      commercial ink-jet printer. The application for the phantom is in the evaluation
      of planar and SPECT scintillation camera images and for validation of Monte Carlo
      simulated images. The accuracy in generating the activity distributions on paper
      sheets is especially important. Here we describe the calibration procedure for
      the ink-jet printer. The goal of the printer calibration is to find the
      relationship between the digital image count (voxel grey level) and its
      corresponding activity on the paper sheets (radioactivity). The relationship
      between the voxel grey level and the radioactivity on the paper sheets (measured
      by scanning technique and well counter) was found to be logarithmic, and a 3rd
      degree polynomial was found to fit the relationship. The distribution of
      radioactivity in the ink cartridge was investigated by pinhole SPECT. The
      distribution of (99m)Tc solution was found to be homogeneous in the ink solution.
      Experimental studies were done directly on Monte Carlo simulated heart images
      from the NCAT phantom. The result showed that the simulated images are similar to
      the images measured using the ink-jet technique. This stack phantom could be a
      promising solution with an advantage that the exact geometry generated in Monte
      Carlo could be imitated in the phantom. The phantom is a very flexible device and
      clearly much more versatile than conventional phantoms which have a fixed
      geometry and spatial limitation.

PMID- 12804046
TI  - Comparison of methods for predicting myelotoxicity for non-marrow targeting I-131
      antibody therapy.
AB  - Although marrow suppression is usually the dose-limiting toxicity in non-marrow
      ablative radionuclide therapy, calculated marrow dose has rarely been used for
      prescribing the radioactivity to be administered. This study assesses the
      correlation of myelotoxicity with mCi/m(2), patient-specific lean body dose,
      marrow dose from blood and body of reference man, or from blood and body using
      the patient-specific mass. Fourteen prostate cancer patients were treated with
      (131)I-CC49. Radioactivity in blood and body was determined and used to calculate
      their contributions to the marrow dose. Platelet nadir expressed as percentage
      (%) of the initial baseline was used as an indicator for myelotoxicity.
      Correlation between platelet nadir (%) and myelotoxicity predictors was
      evaluated. Platelet nadirs (%) varied substantially (5-33%) for a small range of
      injected radioactivity/m(2) (68-78 mCi/m(2), 2.5-2.9 GBq/m(2)). Patient-specific
      total body dose based on lean body mass exhibited a weak correlation (r = 0.48)
      with platelet nadir. Marrow dose from blood and body of reference man had a
      better correlation (r = 0.73). Patient-specific marrow dose from blood and body
      (or lean body) had a similar correlation (r = 0.74 or 0.73). Radioactivity in the
      remainder of the body contributed only 28% of the total dose, and thus changes to
      this dose component had small impact on total marrow dose. Marrow dose was a
      better predictor for myelotoxicity than mCi/m(2) or lean total body dose in this
      non-marrow targeting (131)I-antibody therapy with high blood contributions to
      total dose.

PMID- 12804047
TI  - Crypt cell dosimetry for 99Tcm-sestamibi in a new small intestinal dosimetry
      model.
AB  - The aim of the study was to calculate the absorbed dose to the crypt cells in the
      small intestine from (99)Tc(m)-sestamibi excreted through the intestinal tract.
      The absorbed dose was calculated taking into consideration the biodistribution of
      the radiopharmaceutical in the small intestinal wall and its contents, based on
      data gathered in rats. Absorbed dose calculations were performed using a new
      intestinal model in which S values for crypt cells are given both for the
      intestinal wall and for the intestinal contents as source organs. A maximum of 6%
      of the injected activity was found to be located in the intestinal wall at 30
      minutes after injection and 13% in the intestinal contents at 2 h, resulting in
      an absorbed dose of 8.9 microGy/MBq to the crypt cells. Assuming the activity to
      be located only in the wall, we calculate an absorbed dose to the crypt cells 2.5
      times higher than if all the activity is assumed to be present in the intestinal
      contents. Using the new intestinal dosimetry model, together with detailed
      biokinetic data for the radiopharmaceutical from animal studies, it is possible
      to calculate the absorbed dose to the crypt cells, which is not possible when
      using external imaging.

PMID- 12804048
TI  - Dosimetry of high dose skeletal targeted radiotherapy (STR) with 166Ho-DOTMP.
AB  - A study was undertaken to determine the maximum tolerated dose of (166)Ho-DOTMP
      that could be administered safely, without negatively impacting marrow re
      engraftment, in patients with multiple myeloma treated with melphalan prior to
      transplant. Ho-166 DOTMP is a tetraphosphonate that localizes rapidly to bone
      surface. The Ho-166 physical half-life is 26.8 hr and the maximum beta energy is
      1.8 MeV. Standard dosimetry models were adapted for radiation absorbed dose
      estimates using data obtained from whole body counting of the low abundance
      photons emitted by (166)Ho. Eighty-three patients received high dose (166)Ho
      DOTMP followed by melphalan and transplant of peripheral blood stem cells. Twenty
      five patients also received 8 Gy total body radiation (TBI). Dosages administered
      ranged from 460 to 4476 mCi (166)Ho-DOTMP. Marrow dose was derived using the
      assumption that all radioactivity not excreted by 20 hours was localized to the
      bone surfaces, and applying the Eckerman bone and marrow dose model to the
      calculated bone residence times. The dosimetry of the urinary bladder and kidneys
      was important because of the rapid excretion of the non-targeted radioactivity
      via the urinary pathway. The dynamic bladder model was used for bladder wall
      surface dose, and the ICRP 53 kinetic model was used to model kidney kinetics
      with an additional blood component included. Marrow doses ranged from 13 to 59 Gy
      and successful hematapoietic recovery occurred. Bladder doses ranged from 4.7 to
      157 Gy. Hemorrhagic cystitis occurred in some patients who received more than 40
      Gy to the bladder wall surface. Bladder irrigation was successful in protecting
      patients from bladder toxicity. Kidney doses ranged from 0.5-7.9 Gy. Kidney
      toxicity in the form of thrombotic microangiopathy with renal dysfunction was
      observed, with the severity being related to Ho-166-DOTMP radiation dose and
      probably the dose rate as well. In a future trial, kidney dosimetry will be
      assessed using early serial gamma camera imaging and modifications will be
      implemented to reduce renal toxicity.

PMID- 12804049
TI  - Impact of interpatient pharmacokinetic variability on design considerations for
      therapy with radiolabeled MAbs.
AB  - Radionuclides provide biologically-distributed vehicles for radiotherapy of
      multifocal cancer. Two algorithms, fixed vs individualized, have been used to
      prescribe the therapeutic dose of radionuclide (GBq) for the patient. The
      individualized method for prescribing radionuclide dose takes variations in drug
      pharmacokinetics into consideration, whereas the fixed method depends, in part,
      on documentation that there is little interpatient pharmacokinetic variability
      for the radiolabeled drug. Two data bases, selected to compare iodine-131((131)I)
      and indium-111((111)In) labeled MAbs, were used to assess interpatient
      pharmacokinetic variability and its impact on radionuclide dose prescription.
      Pharmacokinetic data obtained over 7 days for non-Hodgkins lymphoma (NHL)
      patients given (131)I-Lym-1 (n = 46) or (111)In-Lym-1 (n = 13) were used to
      obtain cumulated activities. Although (131)I-Lym-1 often showed greater
      interpatient variability, (111)In-Lym-1 showed several-fold variability for many
      tissues. Both (131)I- and (111)In-Lym-1 had sufficient interpatient variability
      to be significant for radionuclide dose prescription, depending on the dose
      limiting critical tissue. Interpatient variability exceeded intra- and
      interoperator variability and intrapatient variability over time for a single
      institution. In summary, the magnitude of interpatient pharmacokinetic
      variability for (131)I- and (111)In-Lym-1 suggested that an optimally safe and
      effective therapy can be best achieved when radionuclide dose is influenced by
      estimated radiation dose, if the latter is reproducible from institution to
      institution.

PMID- 12804050
TI  - Three-dimensional dose model for the comparison of 177Lu-HuCC49DeltaCH2 and 177Lu
      HuCC49 radioimunotherapy in mice bearing intraperitoneal xenografts.
AB  - Uptake and dose distributions in peritoneal LS174T colon tumor xenografts were
      compared for a humanized construct of the CC49 (HuCC49) high-affinity anti-TAG-72
      monoclonal antibody and a construct with the CH2 region deleted (HuCC49DeltaCH2),
      both labeled with (177)Lu using a PA-DOTA bifunctional chelating agent and
      injected in the peritoneum. Tumors were resected and serially sectioned at 1 h, 4
      h, 24 h, and 48 h postinjection. Between 5 and 24 (average 16) sections were
      retained per tumor for autoradiography. The typical section interval was 340
      microm and thickness was 16 microm. Tumor sections were air dried and placed on
      film and/or phosphor screen. Section images were digitized at 100 microm
      resolution electronically (phosphor screen) or by laser densitometer (film).
      Section images were used to generate tumor surface descriptions and activity
      distributions by reconstructing the activity densities in three dimensions. Three
      dimensional dose-rate calculations, performed using a point kernel for (177)Lu,
      were used to prepare radial histograms describing the variation in dose rate as a
      function of distance from the tumor center to surface. At early times
      postinjection, the (177)Lu-HuCC49DeltaCH2 antibody displayed higher dose rates
      near the tumor surface compared to the (177)Lu-HuCC49 antibody. At 24 h
      postinjection, dose rate distributions appeared similar for both antibodies and
      more uniform than at earlier times. The (177)Lu-HuCC49DeltaCH2 antibody indicated
      improved uniformity at 48 h postinjection. Cell survival calculations based on
      the three-dimensional dose rate distributions favored (177)Lu-HuCC49DeltaCH2 for
      equal injection activities. However the most significant effect was the greater
      injected dose tolerated for the (177)Lu-HuCC49DeltaCH2 antibody based on
      equivalent estimated bone marrow dose.

PMID- 12804051
TI  - Evaluation of (111)In labeled somatostatin analogs for targeted therapy of
      somatostatin receptor positive tumors.

PMID- 12804052
TI  - Additional radiation absorbed dose estimates for Zevalin radioimmunotherapy.
AB  - Zevalin (ibritumomab tiuxetan) radioimmunotherapy is a novel treatment for non
      Hodgkin's lymphoma (NHL). The Zevalin regimen includes 5 mCi (111)In-labeled
      Zevalin on Day 1, followed by serial anterior and posterior planar gamma images
      for imaging or dosimetry. On Day 8, patients receive 0.4 mCi/kg (90)Y Zevalin for
      radioimmunotherapy. Both Zevalin doses are preceded by 250 mg/m(2) rituximab to
      clear peripheral B cells and improve biodistribution of the radiolabeled
      antibody. In a 143-patient, Phase III, randomized study, the Zevalin regimen
      produced a significantly higher overall response rate than rituximab for relapsed
      or refractory, low-grade, follicular, or transformed NHL (80% versus 56%, p =
      0.02). Fifteen patients from the Zevalin arm of this study were randomly selected
      for additional radiation dosimetry. (90)Y residence times were calculated from
      (111)In image analysis data. MIRDOSE3.1 radiation absorbed dose estimates to
      normal tissues were highest for spleen, testes, and liver, with considerably
      lower doses reaching heart, lung, intestines, red marrow, and kidneys. Radiation
      absorbed doses to organs and marrow were within a safe range following
      administration of 0.4 mCi/kg (90)Y Zevalin.

PMID- 12804053
TI  - Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus
      concomitant administration of timolol and dorzolamide.
AB  - The purpose of this study was to compare the efficacy of the fixed-combination
      solution of timolol 0.5%/dorzolamide 2% with the concomitant administration of
      its components, timolol 0.5% twice a day and dorzolamide 2% twice a day. Ninety
      eight patients adequately controlled with a concomitant regimen of timolol and
      dorzolamide were switched to the fixed-combination regimen of the same
      components. Intraocular pressures at baseline and 4 weeks after the change in
      regimen were recorded. The mean baseline intraocular pressure (IOP) was 16.0 +/-
      5.6 mmHg. Four weeks after the change in medication to the fixed-combination
      regimen, the mean IOP was 14.5 +/- 5.6 mmHg. The mean IOP change from baseline
      was -1.5 +/- 3.9 mmHg. The difference between the two treatment modalities was
      found to be statistically significant (p-value < 0.001). Eighty-one (83%)
      patients were considered successfully switched after 4 weeks of fixed-combination
      therapy, and seventeen eyes (17%) were deemed unsuccessful because a rise in IOP
      was detected. In conclusion, the fixed combination of timolol 0.5%/dorzolamide 2%
      twice a day provided equivalent or better intraocular pressure reduction in most
      patients who were successfully controlled on concomitant administration of its
      components, timolol and dorzolamide.

PMID- 12804054
TI  - The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl
      trinor PGF2alpha by human and rabbit ocular tissue.
AB  - Bimatoprost (Lumigan), the ethyl amide derivative of the potent prostaglandin FP
      agonist 17-phenyl-trinor PGF(2alpha), has been reported to be a member of a
      pharmacologically unique class of ocular hypotensive agents. To confirm that
      bimatoprost, which is intrinsically active as an FP prostaglandin agonist, is
      also a prostaglandin analog prodrug, the hydrolysis of bimatoprost by ocular
      tissues was studied by incubating solutions containing bimatoprost with either
      human or rabbit ocular tissue. The ethyl amide group of bimatoprost was
      hydrolyzed by rabbit and human cornea, iris/ciliary body and Thasclera to produce
      the expected carboxylic acid product, 17-phenyl-trinor PGF(2alpha). The rate of
      hydrolysis by human and rabbit cornea and iris/ciliary body is similar, whereas
      the rate of hydrolysis by the sclera is slower in humans than in rabbits. These
      studies show that human and rabbit ocular tissue (cornea, iris/ciliary body and
      sclera) can convert bimatoprost to the potent prostaglandin FP agonist 17-phenyl
      trinor PGF(2alpha). Separate in vitro studies clearly show that both bimatoprost
      and 17-phenyl-trinor PGF(2alpha) have affinity for and are agonists at the human
      FP receptor. Taken together, the data strongly suggests that the ocular
      hypotensive effect of bimatoprost can be attributed to its activity as a
      prostaglandin receptor agonist either directly or through its role as a
      prostaglandin agonist prodrug.

PMID- 12804055
TI  - Effect of changing from concomitant timolol pilocarpine to bimatoprost
      monotherapy on ocular blood flow and IOP in primary chronic angle closure
      glaucoma.
AB  - The aim of the present prospective masked study was to assess the effect of
      bimatoprost monotherapy on ocular blood flow and intraocular pressure (IOP) in
      eyes of primary chronic angle closure glaucoma patients already on concomitant
      timolol and pilocarpine. Thirty two patients of bilateral primary chronic angle
      closure glaucoma (PCACG) on topical timolol 0.5% twice a day and pilocarpine 2%
      three times daily were switched over to bimatoprost 0.03% once daily in both
      eyes. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) were
      recorded before and after starting bimatoprost and were followed up every four
      weeks for three months. Bimatoprost had statistically significant (p < 0.05) mean
      IOP reduction from 19.3 +/- 6.6 to 13.5 +/- 4.5 mmHg (30.5%) and there was
      improvement from 858 +/- 260 to 1261 +/- 321 microL/min (46.8%) in mean pulsatile
      ocular blood flow (p < 0.05). Conjunctival hyperemia (32%) was the most common
      adverse effect of bimatoprost. Bimatoprost 0.03% monotherapy improved ocular
      blood flow and provided a better diurnal IOP control than concomitant timolol
      pilocarpine in eyes with primary chronic angle closure glaucoma and was found to
      be well tolerated.

PMID- 12804056
TI  - Intraocular adenosine levels in normal and ocular-hypertensive patients.
AB  - PURPOSE: Adenosine receptors modulate several ocular responses; however, our
      understanding of factors that influence ocular extracellular adenosine levels is
      limited. The objective of this study was to evaluate how changes in intraocular
      pressure (IOP) influence endogenous levels of the purines adenosine and inosine,
      in the aqueous humor of normal and ocular-hypertensive patients. PATIENTS AND
      METHODS: Informed consent was obtained from 51 individuals undergoing cataract
      extraction or glaucoma surgical procedures. IOP was measured immediately prior to
      surgery. At the start of the surgical procedure, an aqueous sample of 75-100
      microL was obtained. Purine levels were determined by reverse-phase HPLC.
      RESULTS: In normotensive individuals, mean aqueous adenosine and inosine levels
      were 5.2 +/- 1.1 and 19.4 +/- 2.2 ng/100 microL, respectively. No significant
      correlation between IOP and purine concentration was measured in this group. In
      ocular hypertensive individuals, the mean aqueous adenosine and inosine
      concentration was significantly elevated when compared to normotensive
      individuals. In the ocular hypertensive individual, this elevation in adenosine
      level was significantly correlated with IOP (r(2) = 0.42). CONCLUSIONS: These
      results demonstrate that in ocular hypertensive individuals, aqueous adenosine
      concentration is correlated with IOP. As the activation of adenosine receptors
      can modulate IOP and retinal blood flow, adenosine release during periods of
      ocular hypertension may play an important role in the physiological responses to
      elevated IOP.

PMID- 12804057
TI  - Nicotine applied by transdermal patch induced HSV-1 reactivation and ocular
      shedding in latently infected rabbits.
AB  - The identification of factors involved in herpes virus latency and reactivation
      is critical to a better understanding of the mechanisms essential to viral
      neuroinvasiveness and neurovirulence. Recurrent episodes of ocular herpes
      infections cause irreversible corneal scarring and are the primary cause of loss
      of vision due to an infectious agent in industrialized countries. In this study,
      we examined the ability of nicotine, a compound known to be involved in stress
      associated immunomodulation and recognized as one of the most frequently used
      addictive agents, to induce ocular shedding in rabbits latently infected with
      herpes simplex virus type 1 (HSV-1) strain McKrae. New Zealand white rabbits
      latently infected with HSV-1 at 3-4 weeks post-inoculation were randomly divided
      into two groups. The corneas of all rabbits were free of lesions as verified by
      slit lamp biomicroscopy. One group received nicotine by transdermal patch (21
      mg/day) for 20 days and the other group served as the control. Reactivation data
      were obtained by detection of virus in tear film collected by ocular swabbing
      performed concurrently with the administration of nicotine. Compilation of data
      from three separate experiments demonstrated that 16.5% (258/1560) of the swabs
      taken from rabbits treated with nicotine were positive for virus, compared with
      8.3% (53/639) of swabs taken from controls. Rabbits receiving nicotine exhibited
      a significantly (P < 0.0001) higher rate of ocular shedding than controls. The
      concentration of nicotine in the serum was determined at various times (0-24 hrs)
      after new patch replacement. Peak (average) serum level of nicotine was obtained
      8 hours after patch replacement and exhibited a broad range of values (0.233
      microg/mL-6.21 microg/mL). These results suggest that an initial systemic
      exposure to nicotine significantly increases HSV-1 reactivation. Further studies
      are needed to reveal any effects of nicotine dependency and nicotine withdrawal
      on herpesvirus reactivation.

PMID- 12804058
TI  - Potentiation of acetylcholine action by huperzine-A and physostigmine on some
      vertebrate effectors, including human iris sphincter muscle.
AB  - The main objective of this investigation was to compare the acetylcholine
      potentiating action of huperzine-A with acetylcholinesterase inhibitor
      physostigmine on the frog rectus abdominus muscle, rat phrenic nerve diaphragm
      preparation, guinea pig ileum and human iris sphincter muscle. In vitro on the
      frog rectus abdominus muscle, microM of each alkaloid, incubated for 10 min,
      shifted the acetylcholine concentration response curve to the left. At EC(50)
      level, physostigmine potentiated acetylcholine response by 4-fold. The
      potentiation by huperzine-A was 40-fold. The acetylcholine maximum effect,
      relative to the control, increased to approximately 130% by each alkaloid.
      Neurally mediated twitch contraction of the rat diaphragm, a skeletal muscle at 1
      microM was also potentiated more by huperzine-A than that by physostigmine.
      Neuromuscular block by (+)-tubocurarine was reversed more easily by huperzine-A
      than that by physostigmine. On guinea pig ileum, a 30 nM concentration of each
      alkaloid incubated for 5 min potentiated acetylcholine (10 nM) by 42%, and 33%
      for huperzine-A and physostigmine respectively. The difference in potentiation
      between the alkaloids was not significant. At 300 nM of each alkaloid, intrinsic
      indirect contractions were observed on the ileum, where the rate of contraction
      by huperzine-A was faster than that by physostigmine. On the iris sphincter,
      huperzine-A and physostigmine produced a concentration-dependent effect. Maximum
      effect after each alkaloid was achieved at 30 microM. Potentiation of
      acetylcholine response by 0.3 microM huperzine-A after a 10-min incubation was
      greater than that achieved by physostigmine at an equivalent concentration on the
      contralateral iris sphincter. In summary, huperzine-A exhibits greater
      acetylcholine potentiating activity on vertebrate muscles than that produced by
      physostigmine. The results are discussed in relation to the potential therapeutic
      value of huperzine-A.

PMID- 12804059
TI  - Tolerance of ocular iontophoresis in healthy volunteers.
AB  - To evaluate ocular tolerance, healthy volunteers were iontophoresed transclerally
      using novel OcuPhor trade mark hydrogel drug delivery applicators filled with
      balanced salt solution. In this three-period crossover study in 24 male and
      female subjects, 16 subjects received 0 mA and two of the following DC currents:
      0.1, 0.5., 1.0, 2.0, 3.0, or 4.0 mA for 20 min; 6 subjects received 3 mA for 20
      min and 1.5 mA for 40 min (both equivalent to 60 mAmin total charge). Safety and
      tolerance were determined by subjective VAS and objective ophthalmic assessments.
      Subjects were evaluated before and up to 22 hr after dosing. The applicators were
      well-tolerated and no clinically significant changes in symptomology or in
      ophthalmic assessments were seen following exposure to 0-3.0 mA for 20 min or 1.5
      mA for 40 min. At 4.0 mA 2 of 4 subjects reported a burning sensation under the
      applicator during dosing which resolved by 22 hr post-dose; superficial changes
      in fluorescein staining were observed at 1 hr, but not at 22 hr. The OcuPhor
      trade mark system has promise for noninvasive drug delivery to the eye.

PMID- 12804060
TI  - Effects of ketotifen 0.025% and lodoxamide 0.1% on eosinophil infiltration into
      the guinea pig conjunctiva in a model of allergic conjunctivitis.
AB  - The effects of ketotifen and lodoxamide on eosinophil infiltration were assessed
      in a guinea pig model of allergic conjunctivitis. The two active treatments were
      coded in this masked study in which 30 male guinea pigs, sensitized to chicken
      egg albumin (ovalbumin), were randomly assigned to one of three groups: Group 1,
      instillation of 0.9% NaCl into the conjunctival sac of both eyes; Group 2,
      instillation of 0.025% ketotifen into the left eye and 0.9% NaCl into the right
      eye; Group 3, instillation of 0.1% lodoxamide into the left eye and 0.9% NaCl
      into the right eye. Ovalbumin was administered topically to each eye, except in
      Group 1 where it was only applied to the left eye. (111)In-oxine labeled
      eosinophils were injected into the jugular vein of each guinea pig; the animals
      were sacrificed 17 hours after ovalbumin had been applied. The level of
      radioactivity in the ketotifen- and lodoxamide-treated eyes was approximately 60%
      of that in the saline-treated eyes. Moreover, the mean level of radioactivity in
      the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of
      radioactivity in the saline-treated eye of Group 1, which had not been exposed to
      allergen. These results indicate that the therapeutic effects of ketotifen and
      lodoxamide in allergic conjunctivitis may be partly mediated by an inhibitory
      effect on eosinophils.

PMID- 12804061
TI  - Ganciclovir release rates in vitreous from different formulations of 1-O
      hexadecylpropanediol-3-phospho-ganciclovir.
AB  - PURPOSE: To determine the optimal formulation of lipid prodrug, 1-O
      hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV), for intravitreal delivery.
      METHODS: Equal concentrations of crystalline or liposomal HDP-P-GCV were exposed
      to rabbit whole vitreous, core vitreous, peripheral vitreous, human plasma, and
      heat inactivated rabbit vitreous, and the samples were incubated at 37 degrees C
      for one week. Aliquots were taken at day 1, 2, 3, and 7 and subjected to HPLC
      analysis for conversion to GCV. RESULTS: The resultant concentration of GCV from
      crystalline HDP-P-GCV in vitreous was 198 +/- 49 microM (n = 3) at day 1 and 1253
      +/- 248 microM (n = 3) at day 7. The resultant concentration of GCV from the
      liposomal formulation of HDP-P-GCV in vitreous was much lower, yielding a
      concentration of 66 +/- 7 microM (n = 3) at day 1 and 243 +/- 39 microM (n = 3)
      at day 7 (P < 0.001, t Test). When the crystalline HDP-P-GCV was incubated with
      heat-inactivated vitreous, the detectable GCV concentrations were low (22 microM)
      and did not increase over time. The concentration of GCV detected from the
      crystalline HDP-P-GCV in the core vitreous was 19.69 +/- 3.84 microM (n = 3) at
      day 1 and 1537.36 +/- 177.14 microM (n = 3) at day 7. The concentration of GCV
      released from crystalline HDP-P-GCV in peripheral vitreous was 32.86 +/- 5.07
      microM (n = 3) at day 1 and 1805.78 +/- 327.94 microM (n = 3) at day 7.
      Detectable GCV concentration from both core and peripheral vitreous samples
      increased over time, however, the magnitude of GCV release from peripheral
      vitreous samples was higher (P < 0.05, t Test). CONCLUSION: In vitreous, HDP-P
      GCV as a crystalline formulation was converted to GCV more rapidly than liposomal
      formulation of HDP-P-GCV. Vitreous cells may play an important role in the
      metabolism of either formulation of HDP-P-GCV delivered into vitreous.

PMID- 12804062
TI  - Pharmacokinetic profile of topical flunarizine in rabbit eye and plasma.
AB  - The purpose of this study was to determine the aqueous humor, cornea, iris
      ciliary body, retina and plasma levels and pharmacokinetics of a new topical
      formulation containing 0.05% flunarizine upon single drop application. Albino
      rabbits were used and tissue samples were collected at 15, 30, 60, 120 and 240
      min after instillation. Drug concentrations in ocular tissues and plasma were
      measured by gas chromatography assay. After single dose application peak levels
      of drug were achieved at 15 min in cornea and at 30 min in aqueous humor, iris
      ciliary body and retina. Unilateral topical flunarizine caused a significant
      reduction of intraocular pressure in rabbits. The pharmacokinetic profile showed
      a good ocular bioavailability of the drug providing that the new topical
      formulation containing 0.05% flunarizine reach the target tissues at effective
      concentrations and therefore may be use in the treatment of glaucoma.

PMID- 12804063
TI  - Intraocular availability of topically applied mycophenolate mofetil in rabbits.
AB  - The efficacy of mycophenolate mofetil (MMF), a prodrug of mycophenolic acid
      (MPA), in high risk keratoplasties and ocular immune-mediated diseases has been
      shown in recent years. As peroral administration of MMF can cause various side
      effects, topical application should be considered. This study investigates the
      intraocular availability of MMF and MPA in the rabbit eye. An eye drop solution
      (MMF-CD; 1% MMF/10% hydroxypropyl-beta-cyclodextrin (HP-beta-CD)) or a 1% aqueous
      suspension (MMF-SP) was instilled into the lower cul-de-sac of the right eye of
      each rabbit. Rabbits (each group: n = 4) were put down after 30, 60 and 240 min.
      Aqueous humor, vitreous, cornea, sclera, conjunctiva, iris-ciliary-body, and
      plasma were isolated. Several extraction procedures were performed in order to
      quantify the drug by HPLC. The aqueous humor concentration of the active
      metabolite MPA was 24 microg/mL after 30 min for both preparations. The ratio of
      the MPA concentrations after 30, 60, and 240 min was 1 : 2 : 0.07 for MMF-CD and
      1 : 0.6 : 0.04 for MMF-SP, respectively. MPA levels in the cornea were 90.78 /
      56.90 / 4.08 x 10(-6) microg/microg for MMF-CD, whereas MMF-SP resulted in MPA
      levels of 102.65 / 31.18 / 2.59 x 10(-6) microg/microg at the three time points.
      As a high concentration of the active drug MPA in cornea and aqueous humor is
      desired, e.g. following corneal transplantation, the MMF/HP-beta-CD formulation
      could be an useful topical treatment. Furthermore, the present study shows that
      MMF-CD is superior to MMF-SP by increasing intraocular availability.

PMID- 12804064
TI  - Truncated chicken interleukin-1beta with increased biologic activity.
AB  - Chicken interleukin-1beta (ChIL-1beta) is synthesized as a precursor molecule
      that unlike its mammalian counterpart, lacks a typical caspase-1 cleavage site.
      Therefore, it was unclear if proteolytic cleavage of ChIL-1beta can occur and if
      cleavage might modulate the biologic activity of this cytokine. Using an avian
      indicator cell line that carries an NF-kappaB-regulated luciferase reporter gene,
      we established a sensitive and highly specific bioassay for ChIL-1beta.
      Experiments with a rabbit antiserum indicated that the NF-kappaB-stimulating
      activity in supernatants of lipopolysaccharide (LPS)-treated chicken HD-11
      macrophages is largely due to IL-1beta and that proteolytic processing of natural
      and recombinant ChIL-1beta is not very efficient. Functional analyses further
      revealed that cDNAs for either full-length or N-terminally truncated chicken ChIL
      1beta yielded active cytokine. A truncated molecule that closely resembled
      putative mature ChIL-1beta exhibited more than 100-fold enhanced biologic
      activity after expression in mammalian cells, indicating that precursor cleavage
      is indeed of critical importance for maximal activity.

PMID- 12804065
TI  - TNF-alpha and growth hormone resistance in patients with chronic liver disease.
AB  - Liver cirrhosis is characterized by a severe impairment of the growth
      hormone/insulin-like growth factor-1 (GH-IGF-1) axis, that is, acquired GH
      resistance. The condition of the GH-IGF-1 axis in the phase of chronic liver
      disease (CLD) preceding cirrhosis, however, remains uncertain. The origin of GH
      resistance during CLD is multifactorial, and to date, the liver functional mass
      is considered to play a major role. Although proinflammatory cytokines, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, were found
      to be elevated in patients with CLD and were shown to induce a state of GH
      resistance in other disease models, their involvement in the pathogenesis of GH
      resistance during CLD has never been investigated. We characterized the GH-IGF-1
      axis by analyzing the individual components of the axis (GH, IGF-1, IGF-binding
      protein-3 [IGFBP-3], acid-labile subunit [ALS]) and the corresponding ratios
      (GH/IGF-1, GH/IGFBP-3, and GH/ALS) and verified the links with circulating
      proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), in 34 patients with
      CLD and 12 healthy controls. Evolution of CLD from chronic hepatitis (CH, n = 17)
      to cirrhosis (CIR, n = 17) was associated with a progressive increase of GH
      resistance indices (e.g., GH/IGF-1 ratio: controls 0.5 +/- 0.9, CH 15.9 +/- 31.2,
      p < 0.01 vs. controls; CIR 188.4 +/- 282.7 mU/nmol, p < 0.001 vs. CH and
      controls), indicating its onset also in the early stages of CLD. The progressive
      increase in GH resistance indices matched the increase of circulatory TNF-alpha
      (e.g., TNF-alpha vs. GH/IGF-1, r = 0.54, p < 0.001). A similar trend was found
      for IL-6 without reaching statistical significance (r = 0.23, p = 0.13). We found
      undetectable levels of IL-1beta in our sample of patients and controls. We
      conclude that proinflammatory cytokines play an important role in the
      pathogenesis of GH resistance in CLD, but TNF-alpha is a major factor. In
      addition, GH resistance is present in CLD from the early stages. These results
      could begin new therapeutic lines of attack in the management of CLD.

PMID- 12804066
TI  - Inflammatory mediators and skeletal muscle injury: a DNA microarray analysis.
AB  - Traumatic skeletal muscle injury causes a specific sequence of cellular events
      consisting of degeneration, inflammation, regeneration, and fibrosis. The role of
      early posttraumatic mechanisms, including acute inflammatory response, in muscle
      repair is not well understood. In the present study, oligonucleotide microarray
      analyses were used to examine the candidate genes that are involved in these
      early events of the muscle injury/repair process. cDNA was prepared from the
      injured and control tibialis anterior (TA) muscle of mice 24 h postinjury and
      labeled with the fluorescent dye Cy5 or Cy3 prior to hybridization to a DNA
      microarray. The microarray analysis, including 732 genes, was conducted in
      triplicate, and we describe only genes modulated by the injury showing a
      differential expression (both increased and decreased) 1.7-fold or greater (p <
      0.05) from control uninjured TA muscle. Selected expression patterns were
      confirmed by other gene expression detection methods, including real-time reverse
      transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA)
      or immunohistochemistry detection methods. The upregulated genes (2.8%) were
      mainly associated with inflammation, oxidative stress, and cell proliferation,
      whereas the downregulated genes (3.2%) were related to metabolic and cell
      signaling pathways. In addition, the study suggested that chemokines, such as
      monocyte chemoattractant protein-1 (MCP-1), associated with monocyte/macrophage
      influx and activation, are abundantly expressed in postinjured muscle, and they
      might play a role in traumatic muscle injury/recovery processes.

PMID- 12804067
TI  - Synergistic antiviral activity of human interferon combinations in the hepatitis
      C virus replicon system.
AB  - The use of type I interferon (IFN), in combination with ribvirin, to treat
      chronic hepatitis C virus (HCV) infection has many drawbacks that prevent
      widespread application, ultimately leading to a significant unmet clinical need.
      Potential improvements in IFN therapy through targeted delivery, molecular
      alteration, and combination with other agents are ongoing in an attempt to
      decrease adverse effects and increase efficacy. In this report, the HCV replicon
      cell culture system was used to assess potential synergistic antiviral effects of
      multiple IFN species when administered in combination. Quantitative analysis of
      HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and
      qualitative analysis of HCV protein expression were used to measure the antiviral
      efficacy of individual and combination IFN treatments, and synergistic responses
      of IFN combinations were determined through statistical analysis of the TaqMan
      results. We found that when administered simultaneously, type I/II IFN
      combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in
      dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN
      beta) demonstrated a slightly antagonistic profile. The synergistic effect is
      likely due to differential cell surface receptors and signaling pathways employed
      by types I and II IFNs. Conversely, all type I IFN species bind the same receptor
      and signal through similar pathways, possibly accounting for the nearly additive
      response observed. In support of this hypothesis, IFN treatment resulted in
      differential induction of Stat1 phosphorylation at Tyr 701. In conclusion,
      simultaneous type I/II IFN combination treatment may allow an overall decreased
      effective IFN dose, which may reduce the side effect profiles that hinder current
      therapy.

PMID- 12804070
TI  - Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the
      glutathione theory.

PMID- 12804068
TI  - IFN-gamma induction of osteopontin expression in human monocytoid cells.
AB  - Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)-containing cytokine that
      increases macrophage expression of the Th1 cytokines interferon-gamma (IFN-gamma)
      and interleukin-12 (IL-12), and downregulates macrophage expression of IL-10. OPN
      has been implicated in the clearance of mycobacterial infection and in granuloma
      formation. We previously showed decreased OPN expression in the granulomas of
      patients with disseminated mycobacterial infection in the setting of mutation of
      the IFN-gamma receptor-1 (IFNGR-1). These data suggested that IFN-gamma
      critically regulates OPN expression during mycobacterial infection. Herein, we
      characterize the effect of IFN-gamma stimulation on OPN expression by human
      monocytoid cells. By Western blot, ELISA, and Northern blot analysis, IFN-gamma
      treatment of THP-1 cells was shown to induce OPN mRNA and protein expression in a
      time-dependent and dose-dependent manner. The human OPN promoter was amplified by
      PCR using human genomic DNA as a template and transfected into THP-1 cells.
      Compared with control, OPN promoter activity increased by 15-fold after treatment
      with IFN-gamma. Similar induction of OPN was seen in IFN-gamma-stimulated primary
      human blood monocytes. These data show that IFN-gamma stimulates OPN expression
      from monocytoid cells and suggest that OPN may function in a positive feedback
      loop in Th1 inflammation, increasing expression of IFN-gamma, which itself
      upregulates the OPN gene.

PMID- 12804072
TI  - Treating Tibetan refugees in New York City: the healing work of a fellow refugee.

PMID- 12804073
TI  - "Quality profiling" for complementary medicine: the example of a hospital for
      traditional Chinese medicine.
AB  - OBJECTIVE: The goal of the methodological approach of "quality profiling" for
      complementary and alternative medicine (CAM) is to offer an empirical database
      that would enable different participants in the health care system to evaluate
      the quality of a medical provider. METHODS: Quality profiling is a structured way
      of describing quality on the levels of infra-structure, patients, medical
      interventions, outcomes, and quality assurance related to one specific provider.
      As part of a program called "quality management and research," this type of
      profiling constitutes one basic step for generating knowledge in terms of
      evidence-based medicine as well as confidence-based medicine. Quality profiling
      is exemplified by a hospital for Traditional Chinese Medicine in Germany. Within
      1 year all in-patients were included in the database using questionnaires for
      physicians and patients at the time of admission, discharge from the hospital,
      and follow-up inquiries at intervals up to 1 year after discharge. The frequency
      of diagnostic and therapeutic interventions was recorded daily. RESULTS: Data for
      1036 patients (mean age 53 years old, 73% female) were analyzed. The most
      frequent diagnostic categories were musculoskeletal disorders (30%) and
      neurologic disorders (26%). Therapeutic effects were shown in various outcome
      measures such as reduced intensity of complaints, improved quality of life,
      increased satisfaction in lifestyle areas, and fewer days off work. In 6.5% of
      the subjects, adverse events (mostly of minor severity) were recorded.
      CONCLUSIONS: Quality profiles can serve as a basic tool for evaluating provider
      quality when the results are compared with either a predefined standard or with
      profiles of other providers who are offering similar medical services.

PMID- 12804074
TI  - Enhanced nitric oxide concentrations and expression of nitric oxide synthase in
      acupuncture points/meridians.
AB  - OBJECTIVES: The objectives of this study were to examine the distributions of
      nitric oxide (NO) in the skin points (acupoints)/meridian regions and determine
      whether neuronal nitric oxide synthase (nNOS) protein levels were associated with
      NO concentrations in the areas. DESIGN: Low skin resistance points (LSRP) on the
      skin surface in response to electrical stimuli were performed in anesthetized
      adult rats. The skin together with subcutaneous tissue was isolated in meridian
      regions from PC 2 to 6, BL 36 to 57, CV 3 to 22, and GV 2 to 14. Control skin
      tissues were obtained in the areas close to related meridians without containing
      LSRP. Concentrations of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total NO(2)(
      ) plus NO(3)(-) (NO(x)(-)) were quantified in the skin tissues, micropunches of
      brain nuclei, and blood vessels in a blinded fashion. Western blots were also
      conducted using polyclonal anti-nNOS and anti-endothelial nitric oxide synthase
      (eNOS) antibody in the skin tissues. RESULTS: NO(x)(-) and NO(3)(-)
      concentrations were higher (45 +/- 8% and 43 +/- 7% in the CV, 47 +/- 7% and 51
      +/- 9% in the BL, and 47 +/- 8% and 45 +/- 6% in the PC) than those in control
      regions (p < 0.05, n = 6). NO(x)(-) concentrations are 2- to 3-fold greater in
      skin tissues than those in brain regions and blood vessels (p < 0.05, n = 6-8).
      nNOS protein levels were consistently increased in the skin regions of BL, PC,
      and GV meridians compared with their controls (p < 0.05, n = 5-7) but endothelial
      NO synthase expression was not changed. CONCLUSION: This is the first evidence
      showing that NO contents and nNOS expression are consistently higher in the skin
      acupoints/meridians associated with low electric resistance. The results suggest
      that enhanced NO in the acupoints/meridians is generated from multiple resources
      including neuronal NOergic system, and NO might be associated with
      acupoint/meridian functions including low electric resistance.

PMID- 12804075
TI  - Weak extremely high frequency microwaves affect pollen-tube emergence and growth
      in kiwifruit: pollen grain irradiation and water-mediated effects.
AB  - OBJECTIVE: This study was designed to evaluate the effects of weak-intensity
      extremely high frequency (EHF) microwaves in a model system-the plant organism
      pollen grain-lacking the placebo effect, available in large populations, to
      ensure accurate statistical analysis, and whose sensitivity is closely relevant
      to animal and human biology. DESIGN: This study was blinded using an in vitro
      pollen germination technique. SUBJECTS AND STUDY INTERVENTIONS: Pollen of
      kiwifruit (Actinidia deliciosa) was either directly irradiated or grown in a
      medium prepared with irradiated water, using a CromoStim 2000, (PromoPharma,
      Republic of San Marino) designed for EHF microwave resonance therapy (MRT). It
      produces weak intensity EHF radiations (40-78 GHz), either continuous wave (cw)
      or modulated, at a 10 Hz-frequency, with infrared (IR) carried to 635-950 nm, and
      with an impedance (IPD) of 10(-21) W/Hz cm(2) and a power supply from 0 to 20 mW.
      OUTCOME MEASUREMENTS: Pollen-tube emergence was expressed as a percent of grains
      producing a tube and tube elongation was measured at 4 hours of incubation by a
      turbidimetric assay (A(500)) of cultures, expressed as the net absorbance
      increase over time 0. RESULTS: At days 2 and 4 during aging, both percent of
      germination and tube growth significantly and consistently improved over controls
      in kiwifruit pollen grains irradiated for 30 minutes at day 0 at 10 Hz frequency
      with the CromoStim 2000. Highly significant effects, either stimulant or
      inhibitory, were also observed on kiwifruit pollen (stressed or not) growing in a
      medium prepared with water previously irradiated either cw or modulated.
      Irradiated water affected pollen germination immediately and even after several
      days following EHF treatment. CONCLUSIONS: Either direct or indirect EHF
      irradiation performed by the CromoStim 2000 is effective on pollen growth
      processes. In both cases, water seemed to play a primary role. According to the
      quantum electrodynamical coherence theory, our work could also have implications
      for homeopathy, suggesting a key to explain the efficacy of high dilutions and
      succussion procedures.

PMID- 12804076
TI  - Electrodermal measurements for monitoring the effects of a qigong workshop.
AB  - OBJECTIVES: Electrodermal measurements with a Ryodoraku instrument were used to
      monitor the effects of a 2-day qigong workshop on the body energy of
      participants. METHODS: Measurements were made of the relative electrical
      conductivity of 24 acupuncture points on the wrists and feet of 29 subjects. Each
      subject was measured in the morning and afternoon of each day, and the subjects
      served as their own control. RESULTS: The standard deviation of the mean values
      of the Ryodoraku responses of individuals and of the group were less in the
      afternoons than in the mornings with p-values of 0.004 and 0.0001 for the first
      and second days, respectively. The decreases in the values of the standard
      deviations indicate that the balance of the body energy of individuals and the
      group had improved, presumably as a result of the workshop. We also found that
      all Ryodoraku responses were significantly greater in the afternoons than in the
      mornings, a result that is attributed to a circadian rhythm. CONCLUSIONS: The
      improved balance of qi energy in the body of the participants indicates that
      qigong practice has the potential to improve health. Electrodermal measurements
      for monitoring Eastern and Western therapies are discussed.

PMID- 12804077
TI  - Effect of aromatics on lung mucociliary clearance in patients with chronic
      airways obstruction.
AB  - BACKGROUND: Complementary and alternative medicine have become an increasingly
      topical theme in respiratory medicine. Aromatics are a commonly used ingredient
      in a number of proprietary medicines. It is well established that lung mucus
      clearance is impaired in patients with chronic airways obstruction. This study
      investigated whether aromatics delivered by inunction could be objectively shown
      to enhance lung clearance. METHODS: We studied 12 patients with chronic
      bronchitic with a mean standard error (SE) age of 67 (2) years (mean [SE] tobacco
      consumption history of 64 [12] pack-years). We used a randomized, single-blinded,
      placebo-controlled crossover trial within patient design assessing the effect of
      7.5 g of aromatics inunction (compared to a "no-treatment baseline" and to a
      petrolatum "placebo") on lung mucus clearance measured by a standard radioaerosol
      technique. RESULTS: Aromatic treatment significantly enhanced clearance at two
      time points 30 (p < 0.05) and 60 (p < 0.02) minutes postradioaerosol inhalation
      but had no demonstrable further effect over the following 5 hours despite further
      application of the inunction. The clearance improvement (relative to a baseline)
      observed during the first hour of testing was significantly correlated (p < 0.01)
      with the concentration level of aromatics. CONCLUSION: Our data, thus, provide
      objective evidence of a positive effect of aromatics inunction on mucus clearance
      in chronic airways obstruction.

PMID- 12804078
TI  - Effect of ozone therapy on muscle oxygenation.
AB  - BACKGROUND AND OBJECTIVE: Ozone therapy is being used to treat ischemic
      disorders. However, the underlying mechanisms for the success are unknown and the
      therapy has not been accepted fully within conventional medicine. This study
      sought to assess the effect of ozone therapy on resting muscle oxygenation.
      PATIENTS AND DESIGN: Twenty-three (23) patients and 3 volunteers were recruited
      for this prospective study. Systemic ozone therapy was administered by
      autohemotransfusion on three alternate days over 1 week. Tissue oxygenation
      (mmHg) was directly measured in the tibialis anterior muscle using polarographic
      needle electrodes before and after the first and the third ozone therapy session.
      RESULTS: Globally, the differences in oxygenation were not statistically
      significant but there was a significant decrease in the percentage of low
      oxygenated values (pO(2) < 5 mmHg) following ozone sessions (p < 0.02). The
      change in muscle oxygenation following ozone therapy was inversely correlated
      with age (r = -0.398; p = 0.044) and with the initial (baseline pretherapy)
      muscle oxygenation values (r = -0.644; p < 0.001), indicating that the more
      poorly oxygenated muscles benefited most from the therapy. A significant (p =
      0.031) higher oxygenation in these tissues was observed 48 hours after the second
      session. CONCLUSIONS: Ozone therapy can modify oxygenation in resting muscles,
      particularly of those that are most hypoxic. Our results suggest that ozone
      therapy could be used effectively as a complementary treatment of hypoxic and
      ischemic syndromes and that the therapy warrants further investigation for
      possible application in other clinical conditions.

PMID- 12804079
TI  - Sexual effects of puncturevine (Tribulus terrestris) extract (protodioscin): an
      evaluation using a rat model.
AB  - OBJECTIVE: Apart from its claims for improvement of sexual functions in men, the
      puncturevine plant (Tribulus terrestris: TT) has long been considered as an
      energizer and vitalizer in the indigenous system of medicine. Sexual behavior and
      intracavernous pressure (ICP) measurements were taken in rats to scientifically
      validate the claim of TT [containing protodioscin (PTN)] as an aphrodisiac.
      MATERIALS AND METHODS: Forty sexually mature male Sprague-Dawley rats were
      randomly divided into four groups of 10 each. Group I served as a control group
      and groups II, III, and IV were treated with three different doses of TT extract
      (2.5, 5 and 10 mg/kg body weight, respectively), orally, once daily for 8 weeks.
      Weight was recorded and the rats from all four groups were subjected to sexual
      behavior studies with primed females and various parameters namely mount and
      intromission frequencies (MF and IF, respectively), mount, intromission and
      ejaculation latencies (ML, IL, and EL, respectively) as well as postejaculatory
      interval (PEI) were recorded. In addition, blood pressure and ICP were recorded
      for all rats at the end of study. RESULTS: Increases in body weight (by 9, 23,
      and 18% for groups II, III & IV) and ICP (by 43% and 26% for groups III and IV)
      were statistically significant compared to the control group. Increases in MF (by
      27% and 24%) and IF (by 19% and 22%) for the groups III and IV were statistically
      significant. Decreases in ML (by 16%, 23%, and 22% for groups II, III, and IV)
      and PEI (by 20% for group III) were statistically significant compared to the
      control. CONCLUSIONS: The weight gain and improvement in sexual behavior
      parameters observed in rats could be secondary to the androgen increasing
      property of TT (PTN) that was observed in our earlier study on primates. The
      increase in ICP which confirms the proerectile aphrodisiac property of TT could
      possibly be the result of an increase in androgen and subsequent release of
      nitric oxide from the nerve endings innervating the corpus cavernosum.

PMID- 12804080
TI  - The effect of dilution on the rate of hydrogen peroxide production in honey and
      its implications for wound healing.
AB  - OBJECTIVE: Honey is an effective antiseptic wound dressing, mainly the result of
      the antibacterial activity of hydrogen peroxide that is produced in honey by the
      enzyme glucose oxidase. Because the rate of production of hydrogen peroxide is
      known to vary disproportionately when honey is diluted, and dilution of honey
      dressings will vary according to the amount of wound exudate, it is important to
      know more about the production of hydrogen peroxide at different concentrations
      of honey. DESIGN: The rates of hydrogen peroxide production by honey with respect
      to honey dilution were measured in eight different samples of honey from six
      different floral sources. SETTINGS: Honey Research Unit, Waikato University,
      Hamilton, New Zealand. MAIN RESULTS: The maximum levels of accumulated hydrogen
      peroxide occurred in honey solutions diluted to concentrations between 30% and
      50% (v/v) with at least 50% of the maximum levels occurring at 15-67% (v/v). This
      is equivalent to a 10 cm x 10 cm dressing containing 20 mL of honey becoming
      diluted with 10 to 113 mL of wound exudate. Maximum levels of hydrogen peroxide
      reached in the diluted honeys were in the range of 1-2 mmol/L. CONCLUSION:
      Significant antibacterial activity can be maintained easily when using honey as a
      wound dressing, even on a heavily exuding wound. Concentrations of hydrogen
      peroxide generated are very low in comparison to those typically applied to a
      wound, thus, cytotoxic damage by hydrogen peroxide is very low.

PMID- 12804081
TI  - Medical students' attitudes about complementary and alternative medicine.
AB  - OBJECTIVE: To compare the attitudes about complementary and alternative medicine
      (CAM) of medical students from two different medical schools and at different
      stages of their medical training (first and third years). DESIGN: Four-group,
      cross-sectional, self-administered survey study. SETTINGS AND SUBJECTS: Three
      hundred and eleven (311) students from two British medical schools (Newcastle and
      London). OUTCOME MEASURES: Self-reported knowledge of, attitudes about, and
      beliefs about CAM. RESULTS: Third-year students thought CAM overall was less
      effective than first-year students and also were significantly less interested in
      training in CAM techniques. The 43 attitude statements factored into six
      interpretable factors. A medical school x year ANOVA on the factor scores showed
      many results consistent with the first part of the study. First-year students
      seemed more eager to be taught CAM than third-year students, and students at
      Newcastle were more positive about CAM than those at University College London.
      CONCLUSIONS: Education at medical school does influence attitudes to CAM. As
      their orthodox medical training proceeds, medical students seem to increase their
      skepticism about CAM.

PMID- 12804082
TI  - Safety and efficacy of a traditional herbal medicine (Throat Coat) in symptomatic
      temporary relief of pain in patients with acute pharyngitis: a multicenter,
      prospective, randomized, double-blinded, placebo-controlled study.
AB  - OBJECTIVE: To investigate the safety and efficacy of Throat Coat) (Traditional
      Medicinals,) Sebastopol, CA), a traditional demulcent herbal tea, in comparison
      with a placebo tea in the symptomatic treatment of acute pharyngitis. DESIGN:
      Multicenter, prospective, randomized, double-blinded, placebo-controlled, two
      armed, parallel-group clinical trial. SETTINGS: Three primary care clinics in
      Duluth, MN, Madison, WI, and Middleton, WI. SUBJECTS: Patients of both genders
      (>or=18 years of age) with clinical diagnoses of acute pharyngitis.
      INTERVENTIONS: Patients (n = 60) were randomly assigned to receive 5-8 oz of
      Throat Coat (n = 30) or a placebo (n = 30), four to six times daily. The study
      period was 2 to 7 days with a window for the follow-up visit of 2-10 days
      accounting for the variable duration of sore throat symptoms. OUTCOME MEASURES:
      Primary efficacy parameter: sum of pain intensity differences (SPID) for pain in
      throat on swallowing, calculated as the area under the curve (AUC) of pain
      intensity difference scores (assessed at 1 minute, 5 minutes, 10 minutes, 15
      minutes, 20 minutes, and 30 minutes after treatment). Secondary efficacy
      parameter: total pain relief (TOTPAR), calculated as the AUC from time 0
      (baseline) to 30 minutes of pain relief (assessed at 1 minute, 5 minutes, 10
      minutes, 15 minutes, 20 minutes, and 30 minutes). RESULTS: Compared to placebo,
      intensity of throat pain when swallowing was significantly reduced by Throat Coat
      in intention to treat and valid for efficacy analysis (VEA). Significant
      differences in change from baseline pain were observed at 5 min (p = 0.007), 10
      min (p = 0.005), 15 minutes (p = 0.01), 20 minutes (p = 0.05), and 30 minutes (p
      = 0.04) after completion of the first dose (VEA analysis). There was a
      statistically significant improvement of SPID in the Throat Coat-treated group:
      Least square means +/- standard error of the means (SEM) of SPID were -16.5 +/-
      13.9 in the placebo group and -43.8 +/- 11.9 in the Throat Coat-treated group (p
      = 0.012). TOTPAR was also significantly higher in the Throat Coat-treated group:
      Least square means +/- SEM of TOTPAR were 32.4 +/- 12.8 in the placebo group and
      53.6 +/- 10.9 in the Throat Coat-treated group (p = 0.031). This study shows that
      Throat Coat is significantly superior to placebo and provided a rapid, temporary
      relief of sore throat pain in patients with pharyngitis.

PMID- 12804083
TI  - Considerations relating to the epidemiology of human immunodeficiency virus
      infection: the impact of bacterial antigens and consequences for treatment.
AB  - OBJECTIVE: A treatment for patients with human immunodeficiency virus/acquired
      immune deficiency syndrome (HIV/AIDS) is presented, which is based on an
      isopathic method that appears to be effective in eliminating bacterial antigens
      from the body. The concept is based on a new hypothesis concerning the outbreak
      and spread of AIDS in Africa and worldwide. SUBJECTS AND DESIGN: Laboratory data
      are presented from five European and seven African patients with HIV. RESULTS:
      Oral administration of ultra-low doses of a lysate of Staphylococcus aureus Cowan
      I (12c potency) resulted in a significant increase of CD4 T-cell subsets and
      CD4/CD8 ratios in patients with HIV infection as well as in advanced stages of
      HIV disease, concomitant with the improvement of clinical HIV-related symptoms.
      CONCLUSIONS: Based on epidemiologic data, the beginning of the African AIDS
      epidemic is related-to time, place, and circumstances-to the initial large-scale
      introduction of antibiotics in areas of Central Africa that would later comprise
      the AIDS belt. It is concluded that certain antimicrobial agents can enhance the
      formation of persistent bacterial superantigens, which may indicate a link
      between asymptomatic HIV carriers and the development of AIDS. According to this
      view, superantigens and bacterial cell wall components remaining in the body
      after antibiotic treatment cause a permanent activation of the immune system and
      would thus favor T-cell infection and viral replication in HIV-infected
      individuals.

PMID- 12804084
TI  - Goethean science: an alternative approach.
AB  - This paper considers the science of the poet Goethe as furnishing a complementary
      epistemology for complementary and alternative medicine (CAM), standing alongside
      and very different from conventional scientific methodology. Through reference to
      key texts it explores the phenomenological "science of qualities" that aims to
      allow the scientist, through robust training, to appreciate and intuit the
      wholeness inherent in nature, so that Goethe could claim the human being to be
      the most sensitive instrument. Goethe's color theory-a challenge to Newtonian
      thinking-and his study of plants are explored to illustrate a profoundly
      different way of looking at nature that celebrates the subjective and relational
      as a route to perceiving the whole. Ideas toward application of Goethe's approach
      within CAM are considered and the relevance of this approach as an alternative
      methodological enquiry toward consideration of wholeness and healing are offered.

PMID- 12804085
TI  - Global herbal medicine: a critique.
AB  - Herbal medicine finds itself at a crossroads. If it continues to become
      mainstreamed in a commodity-driven health industry, its focus will change from
      craft-based tradition to globalized industry. On the other hand, if the
      fundamental importance of tradition to indigenous and nonindigenous medicine is
      respected, ecologic and cultural issues arise. Central here are the issues
      associated with control of both land and culture. Many indigenous cultures and
      their local ecologies are currently threatened by globalization. Historically,
      successful large corporations have neither respected the environment nor easily
      acknowledged indigenous claims to land and intellectual property, so no easy
      resolution of these conflicts seems likely. Our case study of Mapuche medicine
      allows us to explore the social and cultural conflicts that many practising
      herbalists experience. We argue that because of the basic contradictions
      involved, the protection of cultures and ecologies that underpin the discipline
      must be made a clear priority. We argue that local cultural traditions are
      clearly at odds with a globalizing herbal industry.

PMID- 12804086
TI  - A table-driven, full-sensitivity similarity search algorithm.
AB  - Searching a database for a local alignment to a query under a typical scoring
      scheme, such as PAM120 or BLOSUM62 with affine gap costs, is a computation that
      has resisted algorithmic improvement due to its basis in dynamic programming and
      the weak nature of the signals being searched for. In a query preprocessing step,
      a set of tables can be built that permit one to (a) eliminate a large fraction of
      the dynamic programming matrix from consideration and (b) to compute several
      steps of the remainder with a single table lookup. While this result is not an
      asymptotic improvement over the original Smith-Waterman algorithm, its complexity
      is characterized in terms of some sparse features of the matrix and it yields the
      fastest software implementation to date for such searches.

PMID- 12804087
TI  - Estimating dataset size requirements for classifying DNA microarray data.
AB  - A statistical methodology for estimating dataset size requirements for
      classifying microarray data using learning curves is introduced. The goal is to
      use existing classification results to estimate dataset size requirements for
      future classification experiments and to evaluate the gain in accuracy and
      significance of classifiers built with additional data. The method is based on
      fitting inverse power-law models to construct empirical learning curves. It also
      includes a permutation test procedure to assess the statistical significance of
      classification performance for a given dataset size. This procedure is applied to
      several molecular classification problems representing a broad spectrum of levels
      of complexity.

PMID- 12804088
TI  - The mutation process of microsatellites during the polymerase chain reaction.
AB  - We build a mathematical model for the mutation process of microsatellites during
      polymerase chain reaction (PCR) using the theory of branching processes. Based on
      the model, we develop a method to estimate the mutation rate of microsatellites
      per PCR cycle and the probability of expansion by maximizing a quasi-likelihood
      of the observed data. We show by simulations that the proposed estimation method
      can accurately recover the relationship between the mutation rate and number of
      repeat units. The theoretical basis for the proposed method is also given. We
      apply the method to experimental data on poly-A and poly-CA repeats.

PMID- 12804089
TI  - Statistical methods for analyzing microarray feature data with replications.
AB  - Expression levels in oligonucleotide microarray experiments depend on a
      potentially large number of factors, for example, treatment conditions, different
      probes, different arrays, and so on. To dissect the effects of these factors on
      expression levels, fixed-effects ANOVA methods have previously been proposed.
      Because we are not necessarily interested in estimating the specific effects of
      different probes and arrays, we propose to treat these as random effects. Then we
      only need to estimate their means and variances but not the effect of each of
      their levels; that is, we can work with a much reduced number of parameters and,
      consequently, higher precision for estimating expression levels. Thus, we
      developed a mixed-effects ANOVA model with some random and some fixed effects. It
      automatically accounts for local normalization between different arrays and for
      background correction. The method was applied to each of the 6,584 genes
      investigated in a microarray experiment on two mouse cell lines, PA6/S and PA6/8,
      where PA6/S enhances proliferation of Pre B cells in vitro but PA6/8 does not. To
      detect a set of differentially expressed genes (multiple testing problem), we
      applied the method of controlling the false discovery rate (FDR), which
      successfully identified 207 genes with significantly different expression levels.

PMID- 12804090
TI  - Discovering simple regions in biological sequences associated with scoring
      schemes.
AB  - Let A denote an alphabet consisting of n types of letters. Given a sequence S of
      length L with v(i) letters of type i on A, to describe the compositional
      properties and combinatorial structure of S, we propose a new complexity function
      of S, called the reciprocal complexity of S, as C(S) = (i=1) product operator (n)
      (L/nv(i))(vi) Based on this complexity measure, an efficient algorithm is
      developed for classifying and analyzing simple segments of protein and nucleotide
      sequence databases associated with scoring schemes. The running time of the
      algorithm is nearly proportional to the sequence length. The program DSR
      corresponding to the algorithm was written in C++, associated with two parameters
      (window length and cutoff value) and a scoring matrix. Some examples regarding
      protein sequences illustrate how the method can be used to find regions. The
      first application of DSR is the masking of simple sequences for searching
      databases. Queries masked by DSR returned a manageable set of hits below the E
      value cutoff score, which contained all true positive homologues. The second
      application is to study simple regions detected by the DSR program corresponding
      to known structural features of proteins. An extensive computational analysis has
      been made of protein sequences with known, physicochemically defined nonglobular
      segments. For the SWISS-PROT amino acid sequence database (Release 40.2 of 02-Nov
      2001), we determine that the best parameters and the best BLOSUM matrix are,
      respectively, for automatic segmentation of amino acid sequences into nonglobular
      and globular regions by the DSR program: Window length k = 35, cutoff value b =
      0.46, and the BLOSUM 62.5 matrix. The average "agreement accuracy (sensitivity)"
      of DSR segmentation for the SWISS-PROT database is 97.3%.

PMID- 12804091
TI  - Protein family classification using sparse markov transducers.
AB  - We present a method for classifying proteins into families based on short
      subsequences of amino acids using a new probabilistic model called sparse Markov
      transducers (SMT). We classify a protein by estimating probability distributions
      over subsequences of amino acids from the protein. Sparse Markov transducers,
      similar to probabilistic suffix trees, estimate a probability distribution
      conditioned on an input sequence. SMTs generalize probabilistic suffix trees by
      allowing for wild-cards in the conditioning sequences. Since substitutions of
      amino acids are common in protein families, incorporating wild-cards into the
      model significantly improves classification performance. We present two models
      for building protein family classifiers using SMTs. As protein databases become
      larger, data driven learning algorithms for probabilistic models such as SMTs
      will require vast amounts of memory. We therefore describe and use efficient data
      structures to improve the memory usage of SMTs. We evaluate SMTs by building
      protein family classifiers using the Pfam and SCOP databases and compare our
      results to previously published results and state-of-the-art protein homology
      detection methods. SMTs outperform previous probabilistic suffix tree methods and
      under certain conditions perform comparably to state-of-the-art protein homology
      methods.

PMID- 12804092
TI  - DNA library design for molecular computation.
AB  - A novel approach to designing a DNA library for molecular computation is
      presented. The method is employed for encoding binary information in DNA
      molecules. It aims to achieve a practical discrimination between perfectly
      matched DNA oligomers and those with mismatches in a large pool of different
      molecules. The approach takes into account the ability of DNA strands to
      hybridize in complex structures like hairpins, internal loops, or bulge loops and
      computes the stability of the hybrids formed based on thermodynamic data. A
      dynamic programming algorithm is applied to calculate the partition function for
      the ensemble of structures, which play a role in the hybridization reaction. The
      applicability of the method is demonstrated by the design of a twelve-bit DNA
      library. The library is constructed and experimentally tested using molecular
      biology tools. The results show a high level of specific hybridization achieved
      for all library words under identical conditions. The method is also applicable
      for the design of primers for PCR, DNA sequences for isothermal amplification
      reactions, and capture probes in DNA-chip arrays. The library could be applied
      for integrated DNA computing of twelve-bit instances of NP-complete combinatorial
      problems by multi-step DNA selection in microflow reactors.

PMID- 12804093
TI  - Error-tolerant pooling designs with inhibitors.
AB  - Pooling designs are used in clone library screening to efficiently distinguish
      positive clones from negative clones. Mathematically, a pooling design is just a
      nonadaptive group testing scheme which has been extensively studied in the
      literature. In some applications, there is a third category of clones called
      "inhibitors" whose effect is to neutralize positives. Specifically, the presence
      of an inhibitor in a pool dictates a negative outcome even though positives are
      present. Sequential group testing schemes, which can be modified to three-stage
      schemes, have been proposed for the inhibitor model, but it is unknown whether a
      pooling design (a one-stage scheme) exists. Another open question raised in the
      literature is whether the inhibitor model can treat unreliable pool outcomes. In
      this paper, we answer both open problems by giving a pooling design, as well as a
      two-stage scheme, for the inhibitor model with unreliable outcomes. The number of
      pools required by our schemes are quite comparable to the three-stage scheme.

PMID- 12804094
TI  - Reducing the time complexity of the derandomized evolution strategy with
      covariance matrix adaptation (CMA-ES).
AB  - This paper presents a novel evolutionary optimization strategy based on the
      derandomized evolution strategy with covariance matrix adaptation (CMA-ES). This
      new approach is intended to reduce the number of generations required for
      convergence to the optimum. Reducing the number of generations, i.e., the time
      complexity of the algorithm, is important if a large population size is desired:
      (1) to reduce the effect of noise; (2) to improve global search properties; and
      (3) to implement the algorithm on (highly) parallel machines. Our method results
      in a highly parallel algorithm which scales favorably with large numbers of
      processors. This is accomplished by efficiently incorporating the available
      information from a large population, thus significantly reducing the number of
      generations needed to adapt the covariance matrix. The original version of the
      CMA-ES was designed to reliably adapt the covariance matrix in small populations
      but it cannot exploit large populations efficiently. Our modifications scale up
      the efficiency to population sizes of up to 10n, where n is the problem
      dimension. This method has been applied to a large number of test problems,
      demonstrating that in many cases the CMA-ES can be advanced from quadratic to
      linear time complexity.

PMID- 12804095
TI  - Qualms regarding the optimality of cumulative path length control in CSA/CMA
      evolution strategies.
AB  - Cumulative step-size adaptation (CSA) based on path length control is regarded as
      a robust alternative to the standard mutative self-adaptation technique in
      evolution strategies (ES), guaranteeing an almost optimal control of the mutation
      operator. This paper shows that the underlying basic assumption in CSA--the
      perpendicularity of expected consecutive steps--does not necessarily guarantee
      optimal progress performance for (mu/mu(I), lambda) intermediate recombinative
      ES.

PMID- 12804096
TI  - Locally-adaptive and memetic evolutionary pattern search algorithms.
AB  - Recent convergence analyses of evolutionary pattern search algorithms (EPSAs)
      have shown that these methods have a weak stationary point convergence theory for
      a broad class of unconstrained and linearly constrained problems. This paper
      describes how the convergence theory for EPSAs can be adapted to allow each
      individual in a population to have its own mutation step length (similar to the
      design of evolutionary programing and evolution strategies algorithms). These are
      called locally-adaptive EPSAs (LA-EPSAs) since each individual's mutation step
      length is independently adapted in different local neighborhoods. The paper also
      describes a variety of standard formulations of evolutionary algorithms that can
      be used for LA-EPSAs. Further, it is shown how this convergence theory can be
      applied to memetic EPSAs, which use local search to refine points within each
      iteration.

PMID- 12804097
TI  - General schema theory for genetic programming with subtree-swapping crossover:
      part I.
AB  - This is the first part of a two-part paper which introduces a general schema
      theory for genetic programming (GP) with subtree-swapping crossover. The theory
      is based on a Cartesian node reference system which makes it possible to describe
      programs as functions over the space N(2) and allows one to model the process of
      selection of the crossover points of subtree-swapping crossovers as a probability
      distribution over N(4). In Part I, we present these notions and models and show
      how they can be used to calculate useful quantities. In Part II we will show how
      this machinery, when integrated with other definitions, such as that of variable
      arity hyperschema, can be used to construct a general and exact schema theory for
      the most commonly used types of GP.

PMID- 12804098
TI  - Modification point depth and genome growth in genetic programming.
AB  - The evolutionary computation community has shown increasing interest in arbitrary
      length representations, particularly in the field of genetic programming. A
      serious stumbling block to the scalability of such representations has been
      bloat: uncontrolled genome growth during an evolutionary run. Bloat appears
      across the evolutionary computation spectrum, but genetic programming has given
      it by far the most attention. Most genetic programming models explain this
      phenomenon as a result of the growth of introns, areas in an individual which
      serve no functional purpose. This paper presents evidence which directly
      contradicts intron theories as applied to tree-based genetic programming. The
      paper then uses data drawn from this evidence to propose a new model of genome
      growth. In this model, bloat in genetic programming is a function of the mean
      depth of the modification (crossover or mutation) point. Points far from the root
      are correspondingly less likely to hurt the child's survivability in the next
      generation. The modification point is in turn strongly correlated to average
      parent tree size and to removed subtree size, both of which are directly linked
      to the size of the resulting child.

PMID- 12804099
TI  - Identification and characterization of a novel large insertion/deletion
      polymorphism of 1464 base pair in the human thyroglobulin gene.
AB  - We identified a novel large insertion/deletion (Indel) polymorphism of 1464 bp
      localized in intron 18 of the human thyroglobulin gene. Data from sequence showed
      a high A+T content (62%), two 17-bp long motif repeats, and three different types
      of 10-bp long palindromic sequences. The comparison between these 1464 bp and
      sequences deposited in National Center for Biotechnology Information
      (NCBI)/GenBank database exhibit a nonsignificant degree of homology with any
      previously described sequences. The long polymerase chain reaction (PCR) method
      was used to amplify the genomic DNA region containing intron 17/exon 18/intron
      18/exon 19/intron 19 by primers situated in the introns 17 and 19. The
      amplification generates two fragments of 3.5 and 5.0 kb that correspond to the
      exclusion or inclusion of a 1464-bp segment, respectively. Both variants are thus
      widely represented in the human population; giving allele frequencies of 0.56
      (insertion) and 0.44 (deletion). Finally, the polymorphism was confirmed by
      sequence analysis of the 5.0- and 3.5-kb amplified fragments.

PMID- 12804100
TI  - Increase in immunoglobulin G3-secreting cells in intractable Graves' disease.
AB  - Isotype switching of immunoglobulin (Ig)-secreting cells is regulated by a set of
      cytokines. In the present study, we studied the relation between the number of
      peripheral blood mononuclear cells spontaneously secreting IgG, IgM, IgA, and
      their subclasses and the disease severities in autoimmune thyroid diseases. Ig
      secreting cells were measured by enzyme-linked immunospot (ELISPOT) assay in 99
      euthyroid patients with Graves' disease (GD) or Hashimoto's disease (HD) and 13
      normal subjects. The number of IgG3-secreting cells was significantly higher in
      patients with intractable GD who had been undergoing treatment with antithyroid
      drugs for more than 5 years but who did not go into remission than in patients
      with GD in remission. This number correlated significantly with the serum level
      of thyrotropin receptor antibody (TRAb) in all patients with GD. These data
      suggest that the number of IgG3-secreting cells whose isotype switching is
      stimulated by interleukin (IL)-10 and IL-4 may be related to the disease severity
      of GD and to the level of TRAb after long-term treatment with antithyroid drugs.

PMID- 12804101
TI  - Thyroid stunning.
AB  - Debates regarding thyroid stunning-a phenomenon whereby a diagnostic dose of
      radioiodine decreases uptake of a subsequent therapeutic dose by remnant thyroid
      tissue or by functioning metastases-have been fueled by inconsistent research
      findings. Quantitative studies evaluating radioiodine uptake and qualitative
      studies using visual observations both compare thyroid function on the diagnostic
      scan (DxSCAN) versus the posttreatment whole-body scan (RxWBS). The variability
      of findings may be the result of a lack of consensus in clinical nuclear medicine
      regarding many parameters of radioiodine usage including the need to obtain a
      pretreatment diagnostic scan, appropriate therapeutic dose, time between therapy
      dose administration and DxSCAN, and how successful ablation is measured. In the
      studies considered in this review, those that used (123)I rather than (131)I for
      DxSCAN, allowed less time to elapse between diagnostic and therapy dose, and more
      time between therapy dose and RxWBS (at least 1 week), did not observe stunning.
      However, groups that recognized stunning did not demonstrate any difference in
      outcomes (determined by successful first-time ablation). Whether stunning is a
      temporary phenomenon whereby stunned tissue eventually rejuvenates, or whether
      observed stunning actually constitutes "partial ablation," is yet to be
      delineated.

PMID- 12804102
TI  - Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years
      after their first discovery: unresolved questions.
AB  - Ten years after the first description of activating mutations in the thyroid
      stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning
      thyroid adenomas, there is general agreement in assigning a major pathogenic role
      of this genetic abnormality, acting via the constitutive activation of the cAMP
      pathway, in both the growth and functional characteristic of these tumours. From
      the beginning, however, the pathophysiological and clinical relevance of somatic
      TSHR mutations has been debated and some arguments still exist against a fully
      causative role of these mutations and the practical value of detecting these
      mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some
      major issues will be examined herein, including (a) the frequency of TSHR
      alterations in various reports showing that the genetic abnormality underlying
      the pathogenesis of a substantial subset of thyroid tumours has yet to be
      identified; (b) the limitations of the present experimental models, which suggest
      greater caution in the interpretation of in vitro results; (c) the still
      unresolved question of absence of genotype-phenotype correlation. Clarification
      of these issues may hopefully provide new and useful tools for improving the
      clinical management of this disease.

PMID- 12804103
TI  - Bone metabolism in patients with differentiated thyroid carcinoma receiving
      suppressive levothyroxine treatment.
AB  - AIM: Patients with differentiated thyroid carcinoma (DTC) must receive
      suppressive levothyroxine (LT(4)) therapy for the rest of their lives. The
      literature, however, presents conflicting results on how this affects bone
      metabolism. The aim of this study was to assess the influence of the estrogen
      status and LT(4) therapy, in particular LT(4) dosage in micrograms per kilograms
      (microg/kg), on bone metabolism in female patients with DTC. MATERIAL AND
      METHODS: Three markers of bone metabolism (C-terminal telopeptide of type I
      collagen in serum [SCTx]; N-terminal telopeptide of type I collagen in urine [U
      NTx]; and osteocalcin [OC]) were investigated in four groups: group REF (healthy
      premenopausal female controls), group DTC-ES (premenopausal women with DTC and
      normal estrogen levels), group DTC-ED (postmenopausal women with DTC and estrogen
      deficiency), and group DTC-HRT (postmenopausal women with DTC undergoing hormone
      replacement therapy [HRT]). All patients with DTC were on a well-adjusted
      suppressive LT(4) therapy with TSH levels 0.1 mU/L or less. RESULTS: In group DTC
      ES bone turnover was comparable to group REF, whereas in group DTC-ED, all three
      markers were significantly increased as compared to groups REF and DTC-ES. In
      group DTC-HRT, the HRT normalized U-NTx and OC. However, in this group S-CTx was
      not completely normalized by HRT in all patients, although also significantly
      lowered compared to group DTC-ED. The analysis of LT(4 )dosage per kilogram
      showed that premenopausal DTC-patients had increased markers of bone metabolism
      if LT(4) dosage exceeded 2.6 microg/kg. Estrogen-deficient patients with DTC,
      however, had a much lower critical LT(4) dosage, above which increased markers of
      bone metabolism were seen. CONCLUSION: A well-adjusted suppressive LT(4) therapy
      of less than 2.6 microg/kg and normal estrogen levels do not seem to increase
      bone metabolism in estrogen-sufficient patients with DTC. The normalization of an
      estrogen deficiency by HRT or other antiresorptive therapies and minimal
      suppressive dosages of LT(4) are attempts to optimize the care of patients with
      DTC. In postmenopausal patients with DTC and patients with DTC who require LT(4)
      dosages in excess of 2.6 microg/kg, the information provided by markers of bone
      metabolism may help to prevent bone damage.

PMID- 12804104
TI  - The effects of triiodothyronine on bone metabolism in healthy ambulatory men.
AB  - The purpose of the present study was to determine the effects of supraphysiologic
      doses of triiodothyronine (T(3)) on skeletal metabolism, calcium balance, and the
      calciotropic hormones. Seven healthy, lean men were studied in an inpatient
      metabolic unit over a 63-day period. All volunteers received oral T(3) at doses
      of 50-75 microg/d. There was a prompt and sustained increase in calciuria and an
      overall net negative calcium balance. The pattern of changes in serum
      osteocalcin, urinary deoxypyridinoline (DPD)/creatinine ratio, and serum bone
      specific alkaline phosphatase indicated an early increase in bone resorption
      followed by a late, incomplete compensatory increase in bone formation.
      Cumulative net calcium loss was 18.5 +/- 5.4 g over the 63-day treatment period,
      averaging 218.5 +/- 41.4 mg/d. This represents 0.22% +/- 0.075% of the total
      skeletal calcium content. The cumulative net calcium loss over the 63-day
      treatment period was highly correlated with the change in DPD (r = -0.95, p =
      0.001). Prompt increases in corrected serum calcium values resulted in serum
      intact parathyroid hormone (iPTH) levels decreasing by 30.4% (p = 0.08). Bone
      mineral density showed no change. We conclude that T(3) accelerates bone turnover
      and that bone formation does not increase acutely to prevent bone loss.

PMID- 12804105
TI  - Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with
      subclinical hypothyroidism: effect of treatment with levothyroxine.
AB  - The increased risk for ischemic heart disease (IHD) associated with subclinical
      hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited
      information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a
      significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by
      apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate
      the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy
      controls as well as the influence of levothyroxine substitution therapy on Lp(a)
      values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69
      patients with SH before and after restoration of a euthyroid state and in 83 age-
      and gender-matched healthy controls. Apo(a) isoform size was determined by sodium
      dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and
      development via chemiluminescence. Patients with SH exhibited increased Lp(a)
      levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]),
      but this was not because of differences in the frequencies of apo(a) phenotypes.
      There was no association between thyrotropin (TSH) and Lp(a) levels in patients
      with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high
      (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a)
      concentrations were higher in patients than in the control group (median values
      26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p <
      0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a)
      levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect
      was mainly evident in patients with LMW apo(a) isoforms associated with high
      baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL
      pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even
      though a causal effect of thyroid dysfunction on Lp(a) was not clearly
      demonstrated in patients with SH, levothyroxine treatment is beneficial,
      especially in patients with increased baseline Lp(a) levels and LMW apo(a)
      isoforms.

PMID- 12804106
TI  - An observation trial without surgical treatment in patients with papillary
      microcarcinoma of the thyroid.
AB  - The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has
      resulted in a marked increase in the number of patients with papillary
      microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this
      sophisticated tool. On the other hand, it is debatable whether patients with
      papillary microcarcinoma should always undergo surgery after diagnosis, because a
      high incidence of occult papillary carcinoma has been observed in autopsy
      studies. Thus, we proposed observation without surgical therapy as a treatment
      option in 732 patients diagnosed with papillary microcarcinoma by the above
      technique from 1993 to 2001. One hundred sixty-two patients chose observation and
      were classified as the observation group. During the follow-up period for
      patients in the observation group, more than 70% of tumors either did not change
      or decreased in size compared to their initial size at diagnosis. They enlarged
      by more than 10 mm in 10.2%, and lymph node metastasis in the lateral
      compartments appeared in only 1.2% of patients during follow-up. On the other
      hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the
      observation group who underwent surgery after a period of follow-up were
      classified as the surgical treatment group. Of these 626 patients, lymph node
      dissection was performed in 594 patients, and metastasis was confirmed
      histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients.
      In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years
      after surgery. Our preliminary data suggest that papillary microcarcinomas do not
      frequently become clinically apparent, and that patients can choose observation
      while their tumors are not progressing, although they are pathologically
      multifocal and involve lymph nodes in high incidence.

PMID- 12804107
TI  - Prevalence of cancer in follicular thyroid nodules: is there still a role for
      intraoperative frozen section analysis?
AB  - The optimal surgical management of follicular thyroid nodules and the
      effectiveness of frozen section (FS) analysis in planning the operation are still
      controversial. In this study, we reviewed the prevalence of cancer in 309
      consecutive patients (230 females, 79 males, aged 42 +/- 13 years) with
      follicular nodules at fine-needle aspiration cytology (FNAC) and the efficacy of
      FS evaluation in selecting cancers. On the whole, the prevalence of cancer was
      20.1%; the occurrence of follicular variants of papillary cancer (14.9%) was
      threefold higher than follicular cancers (5.2%). The presence of atypical
      features at FNAC selected nodules with a significantly higher prevalence of
      cancer (46.7%, p = 0.01). FS analysis was performed in 142 patients and
      recognized only 8 of 27 (30%) cancers, one fourth of them with atypia at FNAC. In
      conclusion, this study confirms a 20% overall prevalence of malignancy in
      patients with follicular thyroid nodules. The association of cell atypia with a
      follicular pattern may define a subgroup of nodules more likely to be malignant.
      FS was seldom effective in recognizing cancer confirming the doubt on its cost
      effectiveness in planning the surgical approach. Protocols aimed at a better
      cytologic identification of follicular variants of papillary cancer should be
      considered.

PMID- 12804108
TI  - Autonomous thyroid nodules visualized by positron emission tomography with 18F
      fluorodeoxyglucose: a case report and review of the literature.
AB  - A 41-year-old white female underwent a positron emission tomography with (18)F
      fluorodeoxyglucose (FDG-PET) scan as part of staging follow-up for breast cancer.
      Focal FDG uptake was noted in the right neck. Further evaluation revealed only
      thyroid nodules and subclinical hyperthyroidism. A sodium pertechnetate thyroid
      scan showed two "hot" nodules in the right thyroid lobe corresponding to the
      focal uptake visualized on FDG-PET scan. Technetium-99m uptake was suppressed in
      the remaining thyroid gland. The patient underwent a subtotal thyroidectomy.
      Histopathologic evaluation revealed two hyperplastic nodules in each thyroid
      lobe. We review the literature with regard to FDG-PET imaging of normal and
      diseased thyroid tissue.

PMID- 12804109
TI  - Malignant teratoma of the thyroid: aggressive chemoradiation therapy is required
      after surgery.
AB  - Malignant teratoma of the thyroid gland is exceedingly rare in adults. Many of
      the cases previously reported in the medical literature have fatal outcomes
      because of spread of tumor refractory to treatment. We report a case of primary
      malignant teratoma of the thyroid in a 37-year-old woman. She was treated
      successfully with a combination of surgery, postoperative cis-platinum-based
      chemotherapy and radiation therapy to the neck, with long-term follow-up (10
      years). This case and the modern experience of combined modality therapy in
      extragonadal germ cell tumors of the thyroid and other sites illustrate that
      these tumors should be managed aggressively in order to achieve best results.

PMID- 12804110
TI  - A giant goiter in the 21st century.

PMID- 12804111
TI  - Pemberton's sign associated with a large multinodular goiter.

PMID- 12804112
TI  - A new case of resistance to thyroid hormone caused by a de novo P453T mutation in
      the thyroid hormone receptor gene in an Israeli child.

PMID- 12804114
TI  - Interaction in vitro of type III intermediate filament proteins with Z-DNA and B
      Z-DNA junctions.
AB  - The selection of DNA fragments containing simple d(GT)(n) and composite d(GT)(m).
      d(GA)(n) microsatellites during affinity binding of mouse genomic DNA to type III
      cytoplasmic intermediate filaments (cIFs) in vitro, and the detection of such
      repeats, often as parts of nuclear matrix attachment region (MAR)-like DNA, in
      SDS-stable DNA-vimentin crosslinkage products isolated from intact fibroblasts,
      prompted a detailed study of the interaction of type III cIF proteins with left
      handed Z-DNA formed from d(GT)(17) and d(CG)(17) repeats under the topological
      tension of negatively supercoiled plasmids. Although d(GT)(n) tracts possess a
      distinctly lower Z-DNA-forming potential than d(CG)(n) tracts, the filament
      proteins produced a stronger electrophoretic mobility shift with a plasmid
      carrying a d(GT)(17) insert than with plasmids containing different d(CG)(n)
      inserts, consistent with the facts that the B-Z transition of d(GT)(n) repeats
      requires a higher negative superhelical density than that of d(CG)(n) repeats and
      the affinity of cIF proteins for plasmid DNA increases with its superhelical
      tension. That both types of dinucleotide repeat had indeed undergone B-Z
      transition was confirmed by S1 nuclease and chemical footprinting analysis of the
      plasmids, which also demonstrated efficient protection by cIF proteins from
      nucleolytic and chemical attack of the Z-DNA helices as such, as well as of the
      flanking B-Z junctions. The analysis also revealed sensibilization of nucleotides
      in the center of one of the two strands of a perfect d(CG)(17) insert toward S1
      nuclease, indicating cIF protein-induced bending of the repeat. In all these
      assays, vimentin and glial fibrillary acidic protein (GFAP) showed comparable
      activities, versus desmin, which was almost inactive. In addition, vimentin and
      GFAP exhibited much higher affinities for the Z-DNA conformation of brominated,
      linear d(CG)(25) repeats than for the B-DNA configuration of the unmodified
      oligonucleotides. While double-stranded DNA was incapable of chasing the Z-DNA
      from its protein complexes, and Holliday junction and single-stranded (ss)DNA
      were distinguished by reasonable competitiveness, phosphatidylinositol (PI) and,
      particularly, phosphatidylinositol 4,5-diphosphate (PIP(2)) turned out to be
      extremely potent competitors. Because PIP(2) is an important member of the
      nuclear PI signal transduction cascade, it might exert a regulatory influence on
      the binding of cIF proteins to Z- and other DNA conformations. From this
      interaction of cIF proteins with Z- and bent DNA and their previously detected
      affinities for MAR-like, ss, triple helical, and four-way junction DNA, it may be
      concluded that the filament proteins play a general role in such nuclear matrix
      associated processes as DNA replication, recombination, repair, and
      transcription.

PMID- 12804115
TI  - Stability of Nucleolin protein as the basis for the differential expression of
      Nucleolin mRNA and protein during serum starvation.
AB  - Nucleolin is a nucleolar phosphoprotein that plays a direct role in ribosome
      biogenesis. Our aim was to determine how its activity as a growth-promoting
      factor is coordinated with, if not regulated by, the cell cycle machinery. In
      serum starting and then rescuing these cells with serum, we found that the
      protein level did not drop in the same way that the mRNA level did. In addition,
      although the mRNA level rises during the immediate period during serum rescue,
      the protein level remained the same. We found that the protein level was
      maintained after serum starvation as a result of high stability. There was no
      selective enhanced translation of the remaining amount of Nucleolin mRNA. With
      regard to the constancy in protein level despite the rise in mRNA level during
      serum rescue, there is no concomitant degradation of newly synthesized or old
      protein and synthesis of new protein. Because Nucleolin has been documented to
      bind mRNA, APP mRNA being one among them, we propose a autoregulatory model in
      which Nucleolin regulates the translation of Nucleolin mRNA, such that during a
      period of excess protein, translation is inhibited through direct binding of
      Nucleolin protein to its mRNA.

PMID- 12804116
TI  - Characterization of the ftsZ gene from Ehrlichia chaffeensis, Anaplasma
      phagocytophilum, and Rickettsia rickettsii, and use as a differential PCR target.
AB  - Degenerate primers corresponding to highly conserved regions of previously
      characterized ftsZ genes were used to PCR amplify a portion of the ftsZ gene from
      the genomic DNA of Ehrlichia chaffeensis (ftsZ(Ech)), Anaplasma phagocytophilum
      (ftsZ(Ap)), and Rickettsia rickettsii (ftsZ(Rr)). Genome walking was then used to
      amplify the 5' and 3' termini of the genes. The DNA sequences of the resulting
      amplification products yielded open reading frames coding for proteins with
      molecular masses of 42.0, 45.7, and 48.3 kDa for A. phagocytophilum, E.
      chaffeensis, and R. rickettsii, respectively. These homologs are 20 to 70 amino
      acids longer than the FtsZ proteins characterized in bacteria such as Escherichia
      coli and Bacillus subtilis, but do not possess the large extended carboxyl
      termini found in the FtsZ proteins of Bartonella, Rhizobium, and Agrobacterium
      species. The functional domains important for FtsZ activity are conserved within
      the ehrlichial and rickettsial FtsZ protein sequences. The R. rickettsii FtsZ
      sequence is highly homologous to the FtsZ protein previously described for
      Rickettsia prowazekii (89% identity), and identical to the FtsZ protein of
      Rickettsia conorii. The percent identity observed between the A. phagocytophilum
      and E. chaffeensis FtsZ proteins is only 79% and is particularly low in the
      carboxyl-terminal region (15.8% identity). Primers were designed to PCR amplify a
      portion of the variable carboxyl-terminal region of the ftsZ gene, and used to
      differentiate each agent based on the size of the amplicons: A. phagocytophilum,
      278 bp; E. chaffeensis, 341 bp; and Rickettsia spp., 425 bp.

PMID- 12804117
TI  - Identification and characterization of a consensus DNA binding element for the
      zinc finger transcription factor TIEG/EGRalpha.
AB  - TGFbeta-Inducible Early Gene (TIEG) and the alternatively-transcribed Early
      Growth Response Gene alpha (EGRalpha) share a Cys(2)His(2) three-zinc finger
      region with high homology to Sp1 within its zinc finger region. Three-zinc finger
      transcription factors bind to GC-rich sequences, with small variations in
      consensus sequence between subfamilies. In this work, a consensus sequence was
      identified for TIEG/EGRalpha by expressing and purifying the zinc finger region
      of the protein, and using this to select a binding site from a random
      oligonucleotide library by iterative cycles of nitrocellulose filter binding and
      PCR. A fusion of the TIEG/EGRalpha with the VP16 activation domain supported
      transcription from this site when cloned in front of a heterologous promoter.
      Mutational analysis of the binding site identified a GT-rich core (5'-GGTGTG-3')
      that was necessary for binding, with mutations outside of this region causing
      only a small to moderate decrease in binding.

PMID- 12804118
TI  - Analysis of DNase I-hypersensitive sites in the chromatin of the chicken
      C/EBPbeta gene reveals multiple cis-regulatory elements.
AB  - CCAAT box/enhancer binding protein beta (C/EBPbeta), a member of the basic region
      leucine zipper (bzip) class of transcription factors, plays important roles
      during differentiation of certain cell types, such as liver cells, fat cells and
      myelomonocytic cells. C/EBPbeta is highly expressed in these cell types, and
      activates specific genes during their differentiation. In the hematopoietic
      system, C/EBPbeta expression is restricted to the myelomonocytic lineage. To
      investigate the molecular basis of the cell-type specific expression of the
      C/EBPbeta gene in hematopoietic cells we have cloned the chicken C/EBPbeta gene
      and mapped DNase I hypersensitive sites (DHS) in the vicinity of the gene, using
      myelomonocytic as well as other cell types. We show that there are multiple
      nuclease-sensitive sites, most of which are cell-type specific, suggesting that
      they might act as cell-type specific cis-regulatory DNA elements. To study the
      possible function of these elements we have constructed reporter genes containing
      these sequences and analyzed their activity in different cell types. Our results
      show that several of the nuclease-sensitive regions act as cis-acting stimulatory
      elements in myelomonocytic but not in other cells. Taken together, our data
      suggest that the expression of the C/EBPbeta gene in myelomonocytic cells is
      controlled by multiple cell-type specific cis-acting sequences located both
      upstream and downstream of the gene.

PMID- 12804119
TI  - First complete nucleotide sequence and heterologous gene organization of the two
      rRNA operons in the phytoplasma genome.
AB  - Phytoplasmas are cell-wallless Gram-positive low G + C bacteria belonging to the
      Mollicutes that inhabit the cytoplasm of plants and insects. Although
      phytoplasmas possess two ribosomal RNA (rrn) operons, only one has been fully
      sequenced. Here, we determined the complete nucleotide sequence of both rrn
      operons (designated rrnA and rrnB) of onion yellows (OY) phytoplasma. Both
      operons have rRNA genes organized as 5'-16S-23S-5S-3' with very highly conserved
      sequences; the 16S, 23S, and 5S rRNA genes are 99.9, 99.8, and 99.1% identical
      between the two operons. However, the organization of tRNA genes in the upstream
      region from 16S rRNA gene and in the downstream region from 5S rRNA gene differs
      markedly. Several promoter candidates were detected upstream from both operons,
      which suggests that both operons are functional. Interestingly, both have a
      tRNA(Ile) gene in the 16S-23S spacer region, while the reported rrnB operon of
      loofah witches' broom phytoplasma does not, indicating heterogenous gene
      organization of rrnB within phytoplasmas. The phytoplasma tRNA gene organization
      is similar to that of acholeplasmas, a closely related mollicute, and different
      from that of mycoplasmas, another mollicute. Moreover, the organization suggests
      that the rrn operons were derived from that of a related nonmollicute bacterium,
      Bacillus subtilis. This data should shed light on the evolutionary relationships
      and phylogeny of the mollicutes.

PMID- 12804120
TI  - A major constituent of green tea, EGCG, inhibits the growth of a human cervical
      cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of
      gene expression.
AB  - A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known
      to possess antiproliferative properties. In this study, we investigated the
      anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical
      cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation
      of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory
      effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose
      (ID)(50) of approximately 35 microM. When CaSki cells were further tested for
      EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at
      100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was
      observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at
      35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When
      CaSki cells were tested for their gene expression using 384 cDNA microarray, an
      alteration in the gene expression was observed by EGCG treatment. EGCG
      downregulated the expression of 16 genes over time more than twofold. In
      contrast, EGCG upregulated the expression of four genes more than twofold,
      suggesting a possible gene regulatory role of EGCG. This data supports that EGCG
      can inhibit cervical cancer cell growth through induction of apoptosis and cell
      cycle arrest as well as regulation of gene expression in vitro. Furthermore, in
      vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an
      additional option for a new and potential drug approach for cervical cancer
      patients.

PMID- 12804121
TI  - Psychopharmacology news.

PMID- 12804122
TI  - Reimbursement, managed care, finances, and contracting issues.

PMID- 12804123
TI  - Methodological issues and controversies in clinical trials with child and
      adolescent patients with bipolar disorder: report of a consensus conference.
AB  - OBJECTIVE: To achieve consensus among researchers, pharmaceutical industry
      representatives, federal regulatory agency staff, and family advocates on a
      template for clinical trials of acute mania/bipolar disorder in children and
      adolescents. METHOD: The American Academy of Child and Adolescent Psychiatry, in
      collaboration with Best Practice, convened a group of experts from the key
      stakeholder communities (including adult psychiatrists with expertise in bipolar
      disorder) and assigned them to workgroups to examine core methodological issues
      surrounding the design of clinical trials and, ultimately, to generate a
      consensus statement encompassing: (1) inclusion/exclusion criteria, (2)
      investigator training needs and site selection, (3) assessment and outcome
      measures, (4) protocol design and ethical issues unique to trials involving
      children/adolescents, and (5) regulatory agency perspectives on these
      deliberations. RESULTS: Conference participants reached agreement on 18 broad
      methodological questions. Key points of consensus were to assign priority to
      placebo-controlled studies of acute manic episodes in children and adolescents
      aged 10-17 years, who may or may not be hospitalized, and who may or may not
      suffer from common comorbid psychiatric disorders; to require that specialist
      diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to
      monitor interviewer and rater competency over the course of the trial using
      agreed upon standards; and to develop new tools for assessment, including scales
      to measure aggression/rage and cognitive function, while using the best available
      instruments (e.g., Young Mania Rating Scale) in the interim. CONCLUSIONS:
      Methodologically rigorous, large-scale clinical trials of treatment of acute
      mania are urgently needed to provide information regarding the safety and
      efficacy, in youth, of diverse agents with potential mood-stabilizing properties.

PMID- 12804124
TI  - Methylphenidate treatment in children with borderline IQ and mental retardation:
      analysis of three aggregated studies.
AB  - OBJECTIVE: To determine response of low-IQ children with attention deficit
      hyperactivity disorder (ADHD) symptoms to methylphenidate (MPH). METHODS: An
      aggregated analysis was conducted in 90 children with low IQ who received the
      same dose regimen of MPH in three independent, placebo-controlled studies. Active
      drug and placebo were given from 2 to 4 weeks each. Outcome measures included
      teacher and parent ratings on standardized behavior scales (mean n = 84),
      performance on computer-controlled cognitive-motor tests (n = 62), and measures
      of cardiovascular response (n = 85). RESULTS: Both teachers and parents rated the
      children consistently as being improved on subscales assessing attention,
      overactivity, and conduct problems. Some 44% of the subjects showed at least a
      30% reduction compared with placebo on teacher ratings. MPH improved accuracy on
      several cognitive tests, response speed was increased on some, and seat activity
      declined for one of three tests; heart rate was mildly increased (3.9
      beats/minute) with MPH. Analyses of IQ and mental age as moderator variables
      suggested that lower functional level (especially lower IQ) may be associated
      with a less favorable response to MPH. CONCLUSIONS: Children with low IQ and ADHD
      clearly respond to MPH, but their rate of beneficial response appears to be well
      under that of normal-IQ children and more varied. Different attentional
      mechanisms may moderate response to psychostimulants.

PMID- 12804125
TI  - Rate dependency revisited: understanding the effects of methylphenidate in
      children with attention deficit hyperactivity disorder.
AB  - Although stimulants are widely prescribed for the treatment of attention deficit
      hyperactivity disorder (ADHD), their calming effects are not easily understood.
      One hypothesis derived from preclinical studies is that stimulants exert "rate
      dependent" effects that are inversely related in magnitude and direction to the
      baseline rate of activity or distraction. Previously, compelling support for this
      hypothesis has been lacking. We provide preliminary evidence that methylphenidate
      exerts rate-dependent behavioral effects in children with ADHD. Activity and
      attention were quantified in children with ADHD tested on placebo and different
      doses of methylphenidate using objective measures. Higher doses altered activity
      and attentiveness in a rate-dependent manner after correction for regression-to
      the-mean artifacts. These findings illustrate a clear inverse association between
      symptom severity and degree of therapeutic response that is crucial for our
      understanding of stimulant effects and effective clinical treatment of ADHD.

PMID- 12804126
TI  - Atomoxetine pharmacokinetics in children and adolescents with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: Atomoxetine is indicated for the treatment of attention deficit
      hyperactivity disorder in children, adolescents, and adults. This study was
      conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics
      of atomoxetine in pediatric patients. METHODS: This was an open-label, dose
      titration study in pediatric patients with attention deficit hyperactivity
      disorder. Eligible patients could elect to participate in a single-dose or steady
      state discontinuation pharmacokinetic evaluation including serial plasma sample
      collection over 24 hours. Plasma concentrations of atomoxetine, 4
      hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an
      atmospheric pressure chemical ionization liquid chromatography/mass
      spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated
      using noncompartmental analysis. RESULTS: Twenty-one cytochrome P450 2D6
      extensive metabolizer patients participated in these single-dose and steady-state
      pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma
      concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and
      3.28 hours after a single dose and at steady state, respectively. Minimal
      accumulation occurred in plasma after multiple twice-daily dosing in extensive
      metabolizer pediatric patients, as expected based on single-dose
      pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in
      area under the curve were observed. CONCLUSIONS: The pharmacokinetics of
      atomoxetine in extensive metabolizer patients were well characterized over a wide
      range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients
      and adult subjects were similar after adjustment for body weight.

PMID- 12804127
TI  - Increased amygdala: hippocampal volume ratios associated with severity of anxiety
      in pediatric major depression.
AB  - BACKGROUND: Neurobiologic abnormalities in the temporal lobe, particularly medial
      temporolimbic circuits, have been implicated in the pathogenesis of major
      depressive disorder (MDD). Although MDD commonly emerges during childhood and
      adolescence, to our knowledge, no prior study has examined temporal lobe anatomy
      in pediatric patients with MDD near the onset of illness before treatment.
      METHODS: Volumetric magnetic resonance imaging scans were conducted in 23
      psychotropic drug-naive pediatric patients with MDD, aged 8-17 years, and 23 case
      matched healthy comparison subjects. RESULTS: Pediatric patients with MDD had
      significantly larger left (14%) and right (11%) amygdala:hippocampal volume
      ratios than controls. Increased left and right amygdala:hippocampal volume ratios
      were associated with increased severity of anxiety but not increased severity of
      depression or duration of illness. CONCLUSION: These results suggest that
      alterations in amygdala:hippocampal volume ratios in pediatric MDD may more
      reflect severity of associated anxiety than depression. These results underscore
      the importance of assessment for comorbidity in the study of MDD.

PMID- 12804128
TI  - Long-term safety, tolerability, and clinical efficacy of quetiapine in
      adolescents: an open-label extension trial.
AB  - Quetiapine is a novel, atypical antipsychotic agent that has been shown to
      provide long-term efficacy without serious adverse effects in adults. This is the
      first study of the extended use of quetiapine in adolescents. Five boys and 5
      girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n =
      7) or bipolar disorder with psychotic features (n = 3) were eligible for entry
      into this single-site, 88-week, open-label trial. Subjects had completed a
      pharmacokinetic study over 23 days, during which the dosage of quetiapine was
      increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day)
      (McConville et al. 2000). In the open-label extension of this trial, which
      followed directly after this trial, a physician's choice design allowed for
      flexible dose titration of quetiapine by the study physician to an optimal dose
      for each patient, with ending doses ranging from 300 mg/day to 800 mg/day.
      Concomitant medications, especially for anxiety and/or manic symptoms, were
      allowed as deemed necessary. Tolerability and safety were assessed using clinical
      laboratory tests, physical examinations, measurements of vital signs, interviews
      for selective symptomatology, and electrocardiograms. Psychiatric measurements
      included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global
      Impression (CGI) scale, and the modified Scale for the Assessment of Negative
      Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and
      the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved
      significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence
      of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase
      in mean weight and body mass index at week 64. This long-term study suggests that
      quetiapine is a well-tolerated antipsychotic agent that is efficacious for the
      treatment of symptoms of selected psychotic disorders in adolescents.

PMID- 12804129
TI  - Effectiveness of melatonin in the treatment of sleep disturbances in children
      with Asperger disorder.
AB  - Sleep disturbances are common in patients with Asperger disorder. Although these
      sleep problems are often persistent and may significantly impair the child's
      daytime well-being, no treatment studies have been reported. In this open
      clinical trial, the effectiveness of melatonin was studied in a sample of 15
      children with Asperger disorder (13 boys, 2 girls) aged 6-17 years using several
      questionnaires and actigraph measurements. They included assessments of sleep
      quality, tiredness, and behavior. Melatonin (3 mg/day) was used for 14 days. All
      the measurements were made three times: before the treatment period, during the
      treatment (days 12-14), and 3 weeks after the discontinuation of the treatment.
      The sleep patterns of all the children improved, and half of them displayed
      excellent responses to melatonin. In particular, actigraphically measured sleep
      latency decreased from 40.02 +/- 24.09 minutes to 21.82 +/- 9.64 minutes (p =
      0.002), whereas sleep duration remained steady at 477.40 +/- 55.56 minutes and
      480.48 +/- 50.71 minutes. Despite the short duration of the treatment, behavioral
      measures also displayed a significant improvement, and most of the effect
      disappeared after the discontinuation of the melatonin (p = 0.001). In
      conclusion, melatonin may provide an interesting new and well-tolerated treatment
      option for children with Asperger disorder suffering from chronic insomnia.
      However, these results must be confirmed in a controlled study.

PMID- 12804130
TI  - Hyperglycemia from olanzapine treatment in adolescents.
AB  - The increasing use of olanzapine for treating adolescent patients has brought
      with it greater awareness of the recognized side effects of this medication,
      especially weight gain. Of the reports of glucose dysregulation related to
      olanzapine therapy, only a few pertain to adolescents. We present five cases: two
      youths who consequently suffered from overt diabetes and three who responded with
      glucose dysregulation. According to the Naranjo probability scale, the relation
      of this phenomenon to olanzapine therapy is "probable." We consider the findings
      of the presented case series as justification for regular metabolic follow-up for
      apparently healthy adolescents receiving olanzapine therapy.

PMID- 12804131
TI  - High-dose methylphenidate treatment of attention deficit hyperactivity disorder
      in a preschooler.
AB  - Although attention deficit hyperactivity disorder is thought to be present in
      preschoolers, there are no clear guidelines for dosing stimulant medications in
      this population. This is a case of a 4-year-old boy who was given 108 mg/day
      extended-release methylphenidate (OROS) MPH) (6.1 mg/kg/day) by his caregiver
      with notable behavioral improvement. However, weight loss incurred due to the
      anorexic side effect of the medication led the clinician to decrease his dose to
      72 mg/day OROS MPH (3.7 mg/kg/day). The case highlights that some young children
      with attention deficit hyperactivity disorder treated with MPH may require higher
      doses than would be predicted by weight-based dosing. An increased frequency of
      side effects associated with high doses of MPH necessitates that the clinician
      balance the positive behavioral response of the medication with adverse side
      effects in determining ideal dose.

PMID- 12804132
TI  - Risperidone-associated ejaculatory and urinary dysfunction in male adolescents.
AB  - We report two male adolescents who developed partial or complete retrograde
      ejaculation during risperidone treatment. Additionally, one patient complained of
      bladder outflow obstruction, and the other reported a reduced ejaculatory volume
      and decreased viscosity of semen. On rechallenge with risperidone, patient A
      showed a prompt recurrence of the ejaculatory dysfunction. The side effects were
      highly disturbing and led to reduced treatment compliance in both patients. The
      impact of risperidone, a strong alpha(1)-receptor antagonist, on the adrenergic
      system might induce retrograde ejaculation by altering the sympathetic tonus,
      allowing semen to pass retrogradely into the bladder during ejaculation. The
      reduced ejaculatory volume may be caused by risperidone-induced
      hyperprolactinemia. Clinicians should regularly inquire about sexual dysfunction
      and symptoms suggestive of hyperprolactinemia before starting risperidone
      treatment and regularly thereafter.

PMID- 12804133
TI  - Urinary incontinence with donepezil treatment in hospitalized children and
      adolescents with attention deficit hyperactivity disorder.

PMID- 12804134
TI  - Treating selective serotonin reuptake inhibitor-induced behavioral activation
      with valproate.

PMID- 12804135
TI  - Inability to immunize patients with metastatic melanoma using plasmid DNA
      encoding the gp100 melanoma-melanocyte antigen.
AB  - Immunization with plasmid DNA represents a theoretically attractive method for
      increasing T cell responses against cancer antigens. We administered plasmid DNA
      encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients
      with metastatic melanoma and evaluated immunologic and clinical responses.
      Patients were randomized to receive plasmid DNA either intradermally (n = 10) or
      intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of
      several subcentimeter cutaneous nodules. All other patients had progressive
      disease. Of 13 patients with cells available before and after immunization, no
      patient exhibited evidence of the development of anti-gp100 cell responses using
      in vitro boost assays. The same assays were capable of demonstrating immunologic
      precursors after immunization with fowl poxvirus encoding gp100 or with gp100
      peptides. We were thus unable to demonstrate significant clinical or immunologic
      responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen.

PMID- 12804136
TI  - Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells
      combined with tumor-derived gp96 inhibit tumor growth in mice.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF)-based cancer cell
      vaccines have been shown to be potent inducers of antitumor immunity in several
      murine models, but the antitumor effects on established tumors have been minimal.
      Conversely, the major role of the heat shock protein gp96, localized in the
      endoplasmic reticulum (ER), is to act as a molecular chaperone to assist the
      folding of nascent polypeptide chains in the ER. gp96 derived from tumor cells
      elicits specific protective immunity against parental tumors, presumably through
      the transport of tumor-specific peptides to antigen-presenting cells and the
      maturation of dendritic cells (DCs). However, the therapeutic effects of tumor
      derived gp96 on established tumors have not been promising. The present study
      analyzes the therapeutic effects of GM-CSF gene-transduced Lewis lung cancer
      (LLC/GM) cells combined with LLC-derived gp96 on established wild-type LLC tumors
      in immunocompetent C57BL/6 mice. Therapy with either irradiated LLC/GM cells or
      LLC-derived gp96 barely affected established LLC tumor growth. The antitumor
      effect was significantly enhanced when 1 microg of LLC-derived gp96 was
      administered together with 1 x 10(6) irradiated LLC/GM cells (p < 0.05). The
      antitumor effects of irradiated LLC/GM cells and LLC-derived gp96 required mainly
      CD8(+) T cells. Spleen cells obtained from mice vaccinated with irradiated LLC/GM
      cells and LLC-derived gp96 showed specific CD8 cytotoxic activities against LLC
      cells (specific lysis rate of approximately 28%). This antibody response was not
      associated with a synergic effect of the combination therapy. Moreover, draining
      lymph nodes from mice immunized with irradiated LLC/GM cells and LLC-derived gp96
      contained more migrating mature CD11c(+) cells (higher levels of CD86 and major
      histocompatibility complex [MHC] class II molecules) compared with those from any
      other immunization protocols. These results suggest that the combination of
      irradiated LLC/GM cells and tumor-derived gp96 has potential as a new immunogene
      therapeutic strategy against lung cancer.

PMID- 12804137
TI  - Safety and efficiency of modulating paracellular permeability to enhance airway
      epithelial gene transfer in vivo.
AB  - We evaluated the safety of agents that enhance gene transfer by modulating
      paracellular permeability. Lactate dehydrogenase (LDH) and cytokine release were
      measured in polarized primary human airway epithelial (HAE) cells after lumenal
      application of vehicle, ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'
      tetraacetic acid (EGTA), sodium caprate (C10), or sodium laurate (C12). Lung
      toxicity was assessed after tracheobronchial instillation to murine airways and
      the relative ability of these agents to enhance in vivo adenoviral gene transfer
      was evaluated. Lumenal C12 increased LDH release in vitro, but C10 and EGTA did
      not. Increased levels of interleukin 8 (IL-8) were secreted from EGTA-pretreated
      cystic fibrosis HAE cells after apical application of Pseudomonas aeruginosa
      (10(8) CFU/ml), whereas IL-8 secretion from C10- and C12-pretreated cells was not
      different from controls. In vivo toxicity studies demonstrated no effect of EGTA,
      C10, or C12 on weight gain, lung edema, or bronchoalveolar lavage fluid (BALF)
      albumin. EGTA increased BALF cell counts, neutrophils, and murine (m) macrophage
      inflammatory protein 2, mKC, mIL-6, and mIL-1 beta levels. C10 had no effect on
      BALF cell counts or LDH, but increased murine tumor necrosis factor alpha. C12
      increased BALF LDH, neutrophils, and mIL-6 levels. Histopathological analysis
      revealed mild focal lung inflammation more frequently in the EGTA, C10, and C12
      groups than in vehicle controls, with greater intensity in the C12 group relative
      to the other groups. C10 and C12 also increased airway responsiveness to
      methacholine challenge compared with control and EGTA groups. Adenoviral gene
      transfer to murine trachea in vivo was enhanced more efficiently by C10 than by
      C12 or EGTA. Thus, the different toxicities may permit the selection of agents
      that enhance gene transfer with minimal adverse effects.

PMID- 12804138
TI  - In vivo ligand-inducible regulation of gene expression in a gutless adenoviral
      vector system.
AB  - Transcriptional regulation that is rapid, reversible, and repeatedly inducible
      would greatly enhance the safety and efficacy of many gene therapy strategies. We
      developed a chimeric ligand-inducible regulation system based on the human
      estrogen receptor. This system has two components, the responsive promoter
      driving expression of the transgene of interest, and the ligand-inducible
      chimeric transcription factor. The transcription factor is composed of a novel
      DNA binding domain and a modified estrogen receptor ligand-binding domain. A
      point mutation in the ligand-binding domain significantly reduces estrogen
      binding while allowing binding of the estrogen antagonist, tamoxifen. We used a
      gutless adenoviral vector system and incorporated both components into two
      separate vectors. A single gutless vector encoding both system components was
      also generated. The tamoxifen-mediated induciblity of transgene expression of the
      gutless vector system was compared in vitro and in vivo with the analogous
      components incorporated into early generation, E1/E2a/E3-deficient adenoviral
      vectors. In normal mice, both the gutless vector and early generation systems
      displayed inducibility in the presence of tamoxifen. Importantly, the gutless
      vector system was inducible to extremely high levels, at least four times over a
      2-month period. In contrast, the early generation vector system was inducible
      only once. Furthermore, the early generation system displayed significant
      toxicity, as evidenced by extremely high liver enzyme levels, abnormal liver
      pathology, and rapid loss of vector DNA from the liver, while the gutless vector
      system displayed minimal toxicity. These data directly demonstrate the improved
      in vivo function of the tamoxifen-inducible transcriptional regulation system in
      the context of the gutless adenoviral vectors.

PMID- 12804139
TI  - Radiation improves intratumoral gene therapy for induction of cancer vaccine in
      murine prostate carcinoma.
AB  - Our goal was to convert murine RM-9 prostate carcinoma cells in vivo into antigen
      presenting cells capable of presenting endogenous tumor antigens and triggering a
      potent T-helper cell-mediated immune response essential for the generation of a
      specific antitumor response. We showed that generating the major
      histocompatibility complex (MHC) class I+/class II+/Ii- phenotype, within an
      established subcutaneous RM-9 tumor nodule, led to an effective immune response
      limiting tumor growth. This phenotype was created by intratumoral injection of
      plasmid cDNAs coding for interferon gamma, MHC class II transactivator, and an
      antisense reverse gene construct (RGC) for a segment of the gene for Ii protein (
      92,97). While this protocol led to significant suppression of tumor growth, there
      were no disease-free survivors. Nevertheless, irradiation of the tumor nodule on
      the day preceding initiation of gene therapy yielded 7 of 16 mice that were
      disease-free in a long-term follow up of 57 days compared to 1 of 7 mice
      receiving radiotherapy alone. Mice receiving radiotherapy and gene therapy
      rejected challenge with parental RM-9 cells and demonstrated specific cytotoxic T
      cell activity in their splenocytes but not the mouse cured by radiation alone.
      These data were reproduced in additional experiments and confirmed that tumor
      irradiation prior to gene therapy resulted in complete tumor regression and
      specific tumor immunity in more than 50% of the mice. Increasing the number of
      plasmid injections after tumor irradiation induced tumor regression in 70% of the
      mice. Administering radiation before this novel gene therapy approach, that
      creates an in situ tumor vaccine, holds promise for the treatment of human
      prostate carcinoma.

PMID- 12804140
TI  - Adenovirus serotype 5 fiber shaft influences in vivo gene transfer in mice.
AB  - Adenoviral vectors used in gene therapy are predominantly derived from adenovirus
      serotype 5 (Ad5), which infects a broad range of cells. Ad5 cell entry involves
      interactions with the coxsackie-adenovirus receptor (CAR) and integrins. To
      assess these receptors in vivo, we mutated amino acid residues in fiber and
      penton that are involved in receptor interaction and showed that CAR and
      integrins play a minor role in hepatic transduction but that integrins can
      influence gene delivery to other tissues. These data suggest that an alternative
      entry pathway exists for hepatocyte transduction in vivo that is more important
      than CAR or integrins. In vitro data suggest a role for heparan sulfate
      glycosaminoglycans (HSG) in adenovirus transduction. The role of the fiber shaft
      in liver uptake was examined by introducing specific amino acid changes into a
      putative HSG-binding motif contained within the shaft or by preparing fiber shaft
      chimeras between Ad5 and Ad35 fibers. Results were obtained that demonstrate that
      the Ad5 fiber shaft can influence gene transfer both in vitro and to the liver in
      vivo. These observations indicate that the currently accepted two-step entry
      pathway, which involves CAR and integrins, described for adenoviral infection in
      vitro, is not used for hepatic gene transfer in vivo. In contrast, alpha(v)
      integrins influence gene delivery to the lung, spleen, heart, and kidney. The
      detargeted vector constructs described here may provide a foundation for the
      development of targeted adenoviral vectors.

PMID- 12804141
TI  - Antibody-mediated targeting of replication-competent retroviral vectors.
AB  - Replication-competent murine leukemia virus (MLV) vectors can be engineered to
      achieve high efficiency gene transfer to solid tumors in vivo and tumor
      restricted replication, however their safety can be further enhanced by
      redirecting tropism of the virus envelope. We have therefore tested the targeting
      capability and replicative stability of ecotropic and amphotropic replication
      competent retrovirus (RCR) vectors containing two tandem repeats from the
      immunoglobulin G-binding domain of Staphylococcal protein A inserted into the
      proline-rich "hinge" region of the envelope, which enables modular use of
      antibodies of various specificities for vector targeting. The modified envelopes
      were efficiently expressed and incorporated into virions, were capable of
      capturing monoclonal anti-HER2 antibodies, and mediated efficient binding of the
      virus-antibody complex to HER2-positive target cells. While infectivity was
      markedly reduced by pseudotyping with targeted envelopes alone, coexpression of
      wild-type envelope rescued efficient cellular entry. Both ecotropic and
      amphotropic RCR vector/anti-HER2 antibody complexes achieved significant
      enhancement of transduction on murine target cells overexpressing HER2, which
      could be competed by preincubation with excess free antibodies. Interestingly,
      HER2-expressing human breast cancer cells did not show enhancement of
      transduction despite efficient antibody-mediated cell surface binding, suggesting
      that target cell-specific parameters markedly affect the efficiency of post
      binding entry processes. Serial replication of targeted vectors resulted in
      selection of Z domain deletion variants, but reduction of the overall size of the
      vector genome enhanced its stability. Application of antibody-mediated targeting
      to the initial localization of replication-competent virus vectors to tumor sites
      will thus require optimized target selection and vector design.

PMID- 12804142
TI  - Clinical protocol. Intra-Lesional rF-B7.1 versus rF-TRICOM vaccine in the
      treatment of metastatic cancer.

PMID- 12804144
TI  - Potentiated gene delivery to tumors using herpes simplex virus/Epstein-Barr
      virus/RV tribrid amplicon vectors.
AB  - The development and use of gene transfer techniques creates an opportunity to
      achieve better treatment modalities for numerous disease entities. Promising
      results for treatment in tumor cells in culture and in small animal models have
      been reported. Nevertheless, the lack of widespread vector distribution
      throughout tumor tissue is one of the current limitations for successful clinical
      application of gene therapy paradigms. The use of migratory tumor cells
      themselves as vector delivery vehicles may allow wider vector distribution in
      tumors. In addition, continuous release of retrovirus vectors on-site could
      generate a high local virion concentration over an extended time period with
      consequent increases in transduction efficiency. In this paper, we present in
      culture and in vivo data of a herpes simplex virus-Epstein-Barr virus hybrid
      amplicon vector containing retrovirus vector components (tribrid vector) that
      allows conversion of tumor cells into retroviral producer cells. With this
      method, we were able to achieve a local fourfold amplification of stable
      transgene expression in tumors. The application of this system, which can
      integrate a transgene cassette into tumors with therapeutic bystander effects,
      could increase the local amplification effect to a level of clinical relevance.

PMID- 12804145
TI  - The role of capsid-endothelial interactions in the innate immune response to
      adenovirus vectors.
AB  - Adenovirus (Ad) vectors can produce inflammatory responses at high doses.
      Intravenous administration of an Ad vector expressing green fluorescent protein
      (AdGFP) to naive mice induced a biphasic pattern of liver cytokine/chemokine gene
      expression over 7 days. Tumor necrosis factor alpha (TNF-alpha), macrophage
      inflammatory protein 2 (MIP-2), and interferon gamma-inducible protein 10 (IP-10)
      genes were upregulated, with two distinct peaks of mRNA expression occurring at 6
      hr and 5 days. The administration of transcription-defective AdGFP particles
      induced the early but not the late peak of chemokine/cytokine gene expression,
      confirming that Ad vector-induced inflammation is capsid dependent in the early
      phase and transcription dependent in the late phase. To determine the role of
      adenoviral capsid motifs in the early phase, capsid-modified Ad vectors were
      employed. The intravenous administration of the RGD-deleted Ad vector AdL.PB*,
      the fiber mutant AdL.F*, or the double mutant AdL.F*PB* induced similar levels of
      cytokine/chemokine expression compared with the wild-type vector AdLuc. Kupffer
      cell blockade significantly reduced liver TNF-alpha, MIP-2, and IP-10 gene
      expression and liver inflammation after the administration of AdL.PB* or
      AdL.F*PB*. Fluorescence microscopy of AdLuc- and AdL.PB*-transduced liver at 1 hr
      revealed localization of Ad vectors to liver sinusoids in Kupffer cell-depleted
      mice. AdL.PB* induced less E-selectin and VCAM-1 gene expression in liver,
      confirming reduced endothelial activation in mice receiving RGD-deleted Ad
      vectors. In vitro studies of endothelial cells demonstrated reduced transduction
      and endothelial activation by AdL.PB* compared with AdLuc. These results
      demonstrate that adenovirus capsid RGD motifs are required for efficient
      transduction and endothelial cell activation. Altering vector tropism represents
      a feasible strategy to modulate the innate response to Ad vectors in nontargeted
      tissues.

PMID- 12804146
TI  - Binding of adenoviral fiber knob to the coxsackievirus-adenovirus receptor is
      crucial for transduction of fetal muscle.
AB  - Adenoviral (Ad) infection involves attachment mediated by the Ad fiber protein
      binding to the coxsackievirus-adenovirus receptor (CAR) of a target cell and
      internalization facilitated by the interaction of the Ad penton base protein with
      alpha(v) integrins. To understand the relative importance of the Ad binding and
      internalization steps for the transduction of fetal skeletal muscle, we used a
      panel of genetically modified vectors that specifically ablate the fiber-CAR
      interaction (AdL.F*), the penton base-alpha(v) integrin interaction (AdL.PB*), or
      both (AdL.PB*F*) to transduce embryonic day 16 (E-16) mouse muscle in vivo and
      primary E-16 muscle cells in vitro. Quantification of transgene expression and
      vector genome copies revealed a striking absence of E-16 muscle transduction by
      AdL.F* and AdL.PB*F*. In contrast, fetal muscle transduction with AdL.PB* was not
      significantly different than with the unmodified vector. Similar results were
      observed with in vitro Ad infection studies in primary E-16 muscle cells. From
      these data we conclude that the fiber-CAR interaction is important for the
      transduction of fetal muscle by Ad vectors. The high dependence on fiber-CAR
      binding will impact the development of strategies for Ad vector retargeting to
      achieve muscle-specific transduction in utero.

PMID- 12804147
TI  - Long-term high-level reconstitution of NADPH oxidase activity in murine X-linked
      chronic granulomatous disease using a bicistronic vector expressing gp91phox and
      a Delta LNGFR cell surface marker.
AB  - A murine model of X-linked chronic granulomatous disease (X-CGD), an inherited
      immune deficiency with absent phagocyte NADPH oxidase activity caused by defects
      in the gp91(phox) gene, was used to evaluate a bicistronic retroviral vector in
      which expression of human gp91(phox) and a linked gene for Delta LNGFR, a
      truncated form of human low-affinity nerve growth factor receptor, are under the
      control of a spleen focus-forming virus long-terminal repeat (LTR). Four
      independent cohorts of 11-Gy irradiated X-CGD mice (total, 22 mice) were
      transplanted with or without preselection of transduced X-CGD bone marrow (BM).
      Transplanted mice had high-level correction of neutrophil gp91(phox) expression
      and reconstitution of NADPH oxidase activity. Expression lasted for at least 14
      months in primary transplants, and persisted in secondary and tertiary
      transplants. Both gp91(phox) and Delta LNGFR were detected on circulating
      granulocytes, lymphocytes, lymphoid, and (for Delta LNGFR) red blood cells. Mice
      receiving transduced bone marrow [BM] preselected ex vivo for Delta LNGFR
      expression had high-level (= 80%) reconstitution with transduced cells, with an
      improved fraction of oxidase-corrected neutrophils posttransplant. Analysis of
      secondary and tertiary CFU-S showed that silencing of individual provirus
      integrants can occur even after preselection for Delta LNGFR prior to
      transplantation, and that persistent provirus expression was associated with
      multiple integration sites in most cases. No obvious adverse consequences of
      transgenic protein expression were observed.

PMID- 12804149
TI  - Transferring the financial risks of pharmaceutical benefits from a large health
      care provider in Argentina to a consortium of pharmaceutical companies.
AB  - OBJECTIVE: The National Institute of Social Services for Retirees and Pensioners
      (NISSRP) is a nationwide health care financing agency and service provider in
      Argentina. Among its services, the NISSRP provides outpatient drug coverage to
      more than 3.3 million beneficiaries, mainly senior citizens and disabled persons.
      In 1997, to help cope with its rising costs, the NISSRP agreed to transfer the
      risk for the cost of outpatient medications and cancer-treatment drugs to a
      consortium of pharmaceutical companies in exchange for a fixed monthly payment.
      The objective of this study was to determine the impact that this new approach
      had on three things: (1) the level of expenditures for the medicines that were
      included in the agreement, (2) the pattern of nonrational prescribing for NISSRP
      beneficiaries, and (3) this pattern's relationship with macroeconomic variables
      and the pattern of prescribing for Argentina as a whole. METHODS: We compared
      outpatient-medicine consumption in 1999 with consumption before the agreement
      went into effect. RESULTS: The actual amount that NISSRP beneficiaries spent out
      of-pocket climbed from US$ 336.13 million in 1996 to US$ 473.36 million in 1999,
      an increase of almost 41%. The nominal amount "spent" by the NISSRP in 1999 was
      US$ 601.11 million, versus a real amount of US$ 374.75 million in 1996, an
      "increase" of 60% (that increase for the NISSRP was only theoretical since the
      agreement specified the fixed monthly amount that the NISSRP would have to pay to
      the pharmaceutical consortium). In contrast with the increased real spending by
      NISSRP beneficiaries, Argentina's economy remained stable over the assessed
      period, with the consumer price index even falling by 0.8%. We found high levels
      of nonrational drug use in the NISSRP system in both 1996 and 1999, indicating a
      serious ongoing problem. CONCLUSIONS: An agreement with pharmaceutical companies,
      like the one we have described, might add an element of financial predictability
      for institutions such as the NISSRP. However, such an agreement can easily result
      in an increased economic burden for health care beneficiaries, and without any
      improvement in the services that they receive. This type of agreement requires
      extensive mechanisms for control, follow-up, and updating, and it also risks
      making nonrational drug prescribing the accepted rule. While perhaps feasible,
      the requirements for this kind of agreement are actually very difficult to put
      into place, requiring additional efforts from institutions such as the NISSRP.

PMID- 12804150
TI  - [Resistance to antimicrobials and combination therapy assessment in neonatal
      sepsis].
AB  - OBJECTIVES: To estimate antibiotic resistance among bacterial strains isolated
      from patients with neonatal sepsis from January 1994 through December 1998, and
      to assess the predictive value of the checkerboard method for selecting treatment
      with combination antibiotic therapy in seriously ill patients. METHODS: The study
      of strain susceptibility was carried out by microdilution in broth, and the
      checkerboard method in broth trays was used to assess the efficacy of antibiotic
      combination therapy. RESULTS: Fifty per cent of the strains of coagulase-negative
      Staphylococcus spp. and 37% of S. aureus strains, which are the main pathogens
      involved in neonatal sepsis, were resistant to methycillin. Of these strains,
      94.5% were resistant to several antibiotics. Four strains of coagulase-negative
      Staphylococcus spp. and one strain of Enterococcus faecium were resistant to
      vancomycin (minimal inhibitory concentration = 128 micro g/mL). We noted a high
      probability of clinical efficacy (P < 0.01) with antibiotic combinations having a
      synergistic effect in vitro, whereas antagonic reactions were seen in close
      association with a highly significant probability of clinical therapeutic
      failure. DISCUSSION: The main cause of neonatal sepsis in the Neonatal Intensive
      Care Unit at "America Arias" Hospital in Havana, Cuba, were strains of
      Staphylococcus resistant to methycillin and other antibiotics. In seriously ill
      patients (according to policy established at this institution), the first line of
      treatment is a combination of an aminoglycoside antibiotic and a beta-lactamic
      antibiotic. This study showed that the clinical efficacy of combination
      antibiotic therapy is not determined by the resistance pattern of the strain and
      that good clinical results can be attained, in all likelihood, when a synergistic
      effect can be shown in vitro.

PMID- 12804151
TI  - [Prevalence of and risk factors for cigarette smoking among adolescents in South
      America: a systematic literature review].
AB  - OBJECTIVE: To describe the prevalence of teenage smoking and the factors
      associated with smoking in this age group in South America. METHODS: Searches for
      articles concerning teenage smoking in Latin America were conducted in two
      bibliographic databases: MEDLINE (1966-2002) and Latin American and Caribbean
      Literature on the Health Sciences ("LILACS") (1982-2002). We also reviewed
      governmental and nongovernmental documents and Web sites. From the 315 articles
      that we identified, we considered 45 to be relevant for this paper. RESULTS: In
      each of the countries that we studied, there was often a wide range found in
      prevalence levels, depending in part on the particular age range studied and on
      the definition of smokers that was used. The leading risk factor for teenage
      smoking was smoking among siblings and friends. Additional risk factors were poor
      academic performance, being older, male gender, having paid work, and having
      parents who were separated. CONCLUSIONS: Additional population-based studies with
      teenagers should be carried out, and more uniform criteria for defining smokers
      should be developed.

PMID- 12804152
TI  - [The quality of outpatient services in health facilities in Hidalgo, Mexico, from
      the users' perspective].
AB  - OBJECTIVE: To identify and assess factors associated with the quality of health
      care in hospital outpatient services within the state of Hidalgo, Mexico, based
      on a user survey. METHODS: We performed a cross-sectional, comparative,
      analytical study of 15 public hospitals within the state of Hidalgo, Mexico. The
      sample, which was made up of 9 936 interviewees (power: 85%; significance level:
      95%) was randomly selected among users of outpatient services between July 1999
      and December 2000. We looked at the quality of care using a Likert-type scale.
      The statistical analysis consisted of inconditional logistic regression. RESULTS:
      The quality of care was perceived as being good by 71,37% of users surveyed and
      as bad by 28,63%. Poor quality was primarily perceived in institutions belonging
      to the social security system (39,41% vs. 19,42% in other institutions). Of those
      surveyed, 84,94% said they were satisfied with the care they received, and 49,2%
      said they expected to get better care. In all, 16% claimed they would return to
      the same hospital only because they had no other choice, and 2% said they would
      never return. A higher educational level and a better income showed a direct
      association with the perception of poor quality and discontent with the lenghty
      waiting period (odds ratio [OR]: 2,3; 95% CI: 2,02 to 2,82) and with the
      physician's discourteous attitude (OR: 4,22; 95% CI: 3,6-4,8). CONCLUSIONS: They
      main factors that determine poor quality in health care, according to users, are
      lengthy waiting times before being ushered in, incomplete physical examination
      and diagnosis, difficulty of getting an appointment, and poor treatment on the
      part of services staff.

PMID- 12804153
TI  - Epidemiological aspects of human and canine visceral leishmaniasis in Venezuela.
AB  - OBJECTIVE: To report recent data on the distribution of human and canine visceral
      leishmaniasis (VL) in Venezuela, and to highlight problems associated with
      effective control measures. METHODS: We report the number of cases, incidence
      rate, age and sex distribution, and mortality rates for human VL (HVL) for the
      period of 1995 through 2000, based on National Registry of Leishmaniasis data. We
      carried out serological studies on a total of 3 025 domestic dogs from the 12
      states in Venezuela reporting cases of human VL in this 1995-2000 period and also
      from the state of Yaracuy, where cases were reported earlier during the decade of
      the 1990s. RESULTS: From 1995 through 2000, 242 cases of HVL were reported from
      12 states, in various sections of Venezuela. There was a relatively stable
      national incidence rate of 0.2 cases per 100 000 persons per year. Of the 242
      cases, 26.0% were from Margarita Island, one of the three islands that make up
      the state of Nueva Esparta (Margarita Island was the only one of the Nueva
      Esparta islands that had HVL cases). Over the 1995-2000 period, the annual
      incidence rates for Nueva Esparta ranged from 1.7 to 3.8 cases per 100 000
      population. Males in Venezuela were more frequently affected (59.5%) than were
      females (40.5%). In terms of age, 67.7% of the VL patients were </= 4 years of
      age, and 80.6% were younger than 15 years. The mortality rate among the persons
      with VL was 7.85% during the 1995-2000 period. Serological screening with rK39
      antigen of 1 217 dogs from Margarita Island found a 28.5% positivity rate
      (testing of dogs was not done on the two other islands of Nueva Esparta). In
      contrast, the rate was 2.8% in the 1 808 samples from dogs from 12 states on the
      mainland. CONCLUSIONS: Human and canine VL are unevenly distributed in Venezuela.
      The distribution may reflect such factors as differences among the states in
      human population density, vector density, and the presence or absence of other
      trypanosomatidae. Particularly high infection rates in very young children as
      well as in domestic dogs occur in semiurban communities of Nueva Esparta, where
      other human-infecting trypanosomatidae have not been reported. Control measures
      related to limiting canine infection might contribute to disease control where VL
      infections are frequent. Reducing VL mortality requires increased awareness among
      medical professionals of the possibility of VL in the differential diagnosis of
      hepato-splenic syndromes, particularly in children.

PMID- 12804154
TI  - [Analysis of an outbreak of viral meningitis in the province of Tucuman,
      Argentina].
AB  - OBJECTIVE: To confirm the occurrence of an outbreak of viral meningitis in 1996
      in the province of Tucuman, Argentina, and to study the outbreak's
      epidemiological characteristics. METHODS: We analyzed information from the
      National Epidemiological Surveillance System of the Ministry of Health (MOH) of
      Argentina for 1994-1998 that had been provided by the MOH's Bureau of
      Epidemiology. We calculated incidence rates using population estimates for the
      years 1994-1998 developed by the National Statistics and Census Institute, based
      on the 1991 census. We studied frequencies with contingency tables, using the chi
      square method with Yates' correction. Results were considered significant when P
      < 0.05. RESULTS: We confirmed the occurrence of an outbreak of 189 cases of viral
      meningitis between 11 February and 18 May 1996. The incidence of cases in Tucuman
      province increased between 1995 and 1996, from 0.5 to 19.3 cases per 100 000
      person-years. That 1996 rate in Tucuman was significantly higher than what was
      seen in the rest of the country (2.8 cases per 100 000 person-years). Of the 189
      cases, 142 of them (75.1%) occurred in children less than 9 years old. Out of 111
      samples studied, 65 of them (58.6%) were enterovirus-positive. Through reverse
      transcription-nested polymerase chain reaction, enteroviruses were found in 66.3%
      (53/80) of the cases studied by this method, versus in only 29.6% (24/81) of the
      cases studied through viral isolation. In the 22 samples that were serotyped,
      echovirus type 4 was identified in 15 of them (68%): 5 by isolation, 3 by
      sequencing, and 7 by both methods. During the Tucuman outbreak, at least 56% of
      the cases were hospitalized. This viral meningitis outbreak shows the capacity of
      enteroviruses to spread and cause disease. CONCLUSIONS: The use of molecular
      methods makes it possible to rapidly diagnose the etiological virus and to better
      control an outbreak. Recognizing this outbreak in Tucuman sooner could have
      averted the majority of the hospitalizations and the indiscriminate use of
      antibiotics.

PMID- 12804157
TI  - [The International Association of Tobacco Growers attacks WHO].
AB  - The International Association of Tobacco Growers (IATG) has publicly blamed WHO's
      tobacco control policies for a decline in the amount of land where tobacco is
      grown in the Americas and for the fact that many farmers have lost a way to make
      a living. Contrary to these allegations, the surface of land where tobacco is
      grown and the production of tobacco have increased between 1990 and 2000 (from
      471 975 to 505 636 hectares and from 703 431 to 868 302 metric tons,
      respectively). Furthermore, the IATG's internal documents point to the cause of
      the declining harvests observed in some countries as being the drop in prices
      that has been triggered by surplus production on a global scale. According to
      internal documents belonging to the tobacco industry, the IATG is a public
      relations agency that was created by the industry as its spokesman in developing
      countries in an effort to curb tobacco control initiatives. WHO aims to reduce
      the use of tobacco products and the morbidity and mortality that are attributable
      to such use, a measure which will have no impact on the current generation of
      tobacco growers because, even if the prevalence of smoking does decline, the
      total number of smokers will continue to grow due to the overall increase in the
      size of the population.

PMID- 12804158
TI  - World Health Assembly to consider global treaty on tobacco control. 2003.

PMID- 12804159
TI  - Adverse reaction potential of three measles-mumps-rubella combination vaccines.

PMID- 12804161
TI  - Quantitative ecology of ticks as a basis for transmission models of tick-borne
      pathogens.
AB  - Tick population ecology is the basis of spatiotemporal variation in the risk of
      infection by tick-borne pathogens. The continental distribution of tick-borne
      encephalitis (TBE) in Europe is statistically associated with a specific pattern
      of the seasonal dynamics of Ixodes ricinus, and a particular characteristic of
      the seasonal land surface temperature profile. A tick population model would
      allow us to move from this statistical analysis to a biological, process-based
      model for TBE virus and the many other pathogens vectored by Ixodes spp. ticks in
      Europe and the United States. Long-term field data on I. ricinus are analyzed to
      provide empirical estimates of rates of the major demographic processes,
      development, questing, attachment to hosts, and mortality.

PMID- 12804162
TI  - The Lyme disease vaccine takes its toll.
AB  - Vaccination with Borrelia burgdorferi outer surface protein (Osp) A can induce a
      protective response against Lyme disease and serves as a model to understand the
      generation of protective immune responses against the spirochete. The innate
      response to pathogens is activated by specific Toll-like receptors (TLRs) that
      recognize distinct pathogen-associated molecular patterns. TLR2 is of particular
      interest for B. burgdorferi research because TLR2 recognizes several pathogen
      associated molecular patterns, including lipoproteins. TLR2 may form heterodimers
      with TLR6 to identify diacylated lipoproteins, while TLR2 works in concert with
      TLR1 to recognize triacylated lipoproteins such as OspA. We will discuss the role
      of TLR1/2 in the development of responses to OspA in TLR1-and TLR2-deficient
      mice, and in selected individuals that received the OspA vaccine. While > 95% of
      human OspA-based Lyme disease vaccine recipients develop OspA antibodies, a very
      small group of individuals did not develop detectable humoral responses against
      OspA. We demonstrated that this hyporesponsiveness to OspA vaccination was
      associated with decreased cell surface expression of TLR1. Moreover, TLR1- and
      TLR2-deficient mice did not develop significant levels of OspA antibodies
      following vaccination with OspA, providing a correlation with human
      hyporesponsiveness to OspA. These data suggest that defects in the TLR1/2
      signaling pathway are associated with an impaired ability to generate antibodies
      following immunization with OspA lipoprotein.

PMID- 12804163
TI  - Direct detection methods for Lyme Borrelia, including the use of quantitative
      assays.
AB  - Direct detection of Borrelia burgdorferi sensu lato, the etiologic agent of Lyme
      borreliosis, is the most reliable laboratory diagnostic tool. Several methods
      have been developed for direct detection of B. burgdorferi in infected vectors,
      host tissues, and clinical specimens from patients with Lyme borreliosis. These
      include microscope-based assays, antigen detection assays, in vitro cultivation,
      and nucleic acid-based detection of B. burgdorferi. The sensitivity and
      specificity of these methods depend on various factors and are also variable
      among laboratories. To date, only in vitro cultivation of B. burgdorferi has been
      widely accepted to confirm clinical diagnosis of Lyme borreliosis. Nevertheless,
      various polymerase chain reaction-based molecular assays have shown increasing
      significance in the laboratory diagnosis of Lyme borreliosis because of their
      high sensitivity, specificity, and capability for quantification and typing of
      spirochetes in clinical specimens. In this review, the currently available
      methods for direct detection of B. burgdorferi in clinical samples and
      quantitative analysis of spirochete load in different biological sources are
      discussed.

PMID- 12804164
TI  - Diagnosis of human granulocytic ehrlichiosis: state of the art.
AB  - Human granulocytic ehrlichiosis is an emerging zoonosis caused by Anaplasma
      phagocytophilum and transmitted through the bite of infected Ixodes scapularis.
      It is prevalent in the Midwest and Northeast United States and also in Europe,
      and it presents as a nonspecific febrile illness a few days after a tick bite
      usually between late spring and fall. Most cases present in adult patients with a
      mild form of the disease, although it can be severe with multiorgan failure,
      particularly in the elderly and in the immunocompromised. Routine laboratory
      abnormalities include leukopenia with a left shift, lymphopenia, and
      thrombocytopenia. These abnormalities are more frequently present during the
      first week of illness and then tend to normalize; therefore their absence should
      not exclude the diagnosis. Specific tests to confirm the diagnosis during the
      acute phase include microscopic detection of morulae in granulocytes, culture of
      A. phagocytophilum, and polymerase chain reaction. Of these methods, culture
      appears to have the greatest sensitivity during the acute phase prior to
      antimicrobial treatment. Serology has an important role in the confirmation of
      the diagnosis when used in paired specimens and when high cutoff titers by
      indirect fluorescence antibody assay (> or = 640) are used to diagnose a recent
      infection.

PMID- 12804165
TI  - Nervous system Lyme disease.
AB  - Nervous system involvement in Lyme borreliosis is a much-feared, often
      misunderstood disorder. Both the peripheral and central nervous systems may be
      involved, typically in a multifocal, patchy fashion, perhaps suggesting a
      vasocentric mechanism. Clinical manifestations vary widely, depending on the site
      and severity of involvement. Although neurologic manifestations observed in
      Europe differ somewhat from those reported in the United States, there are also
      striking similarities, permitting some generalization of information obtained in
      each population. In general, diagnosis of neurologic disease requires objective
      evidence of nervous system damage, and must be differentiated from both
      psychiatric disorders and metabolic encephalopathies, both of which typically
      occur in the absence of significant neurologic damage or infection. Laboratory
      confirmation of nervous system involvement by Borrelia burgdorferi has
      limitations. However, neurophysiologic testing of the peripheral nervous system,
      imaging of the neuraxis, and examination of the cerebrospinal fluid can all be
      informative. In contrast, to date functional brain imaging has been of limited
      specificity. Treatment with one of several straightforward antimicrobial
      regimens, typically 2-4 weeks in duration, generally results in microbiologic
      cure. Although some symptoms may persist after this, the data do not suggest that
      these are responsive to further antimicrobial therapy.

PMID- 12804166
TI  - Diversity of Ixodes-borne Borrelia species--clinical, pathogenetic, and
      diagnostic implications and impact on vaccine development.
AB  - Among Borrelia spirochetes carried by hard ticks belonging to the various Ixodes
      species, at least 10 species can be distinguished. Of these, Borrelia burgdorferi
      sensu stricto is involved in human Lyme borreliosis in North America and Europe,
      and Borrelia garinii and Borrelia afzelii in human disease in Europe and Asia.
      The pathogenetic significance of the other species is uncertain. Although some of
      the Borrelia species are restricted to certain tick species, Ixodes ricinus, the
      vector of Lyme borreliosis in Europe, can be infested by at least five different
      species, including all three pathogenic species. There is evidence that different
      Borrelia species are preferentially found in different hosts: In Europe, B.
      afzelii is frequently found in small mammals, whereas B. garinii and Borrelia
      valaisiana are often found in birds. This could very well be related to
      differential sensitivity of these species to complement-mediated bactericidal
      activity of different hosts. Borrelial complement regulator acquiring proteins,
      among them OspE or Erp proteins, bind to host factor H and related proteins, and
      this binding protects against activation of complement by the spirochetal
      surface. The binding is different for proteins originating from different species
      and is also depending on the host origin of factor H. In Europe, B. garinii is
      mainly found in neuroborreliosis, whereas in skin disease B. afzelii is more
      frequently found. The reason is unclear. The majority of human sera cross-react
      between proteins of different Borrelia species, but some sera react only with
      proteins from one of the species. This holds especially for reactivity with OspC.
      A vaccine against B. burgdorferi sensu stricto has been licensed, but was
      recently redrawn from the market because of commercial reasons. A vaccine
      protecting against all three pathogenic species is not yet available.

PMID- 12804167
TI  - Controlled trials of antibiotic treatment in patients with post-treatment chronic
      Lyme disease.
AB  - Some patients have persistence of profound fatigue, myalgias, arthralgias without
      arthritis, dysesthesia/paresthesia, and mood and memory disturbances after
      standard courses of antibiotic treatment for Lyme disease. This constellation of
      symptoms has been variously referred to as "chronic Lyme disease," "post-Lyme
      disease syndrome," and "post-treatment chronic Lyme disease." Persistent symptoms
      have been reported in patients who are seropositive for IgG antibodies against
      Borrelia burgdorferi as well as in patients who are seronegative. The cause or
      causes of persistent symptoms in these patients have not been clearly defined and
      are controversial. Because of the temporal association of these symptoms with
      infection with B. burgdorferi, some patients have been treated with prolonged
      courses of antibiotics. Case reports and uncontrolled trials have reported the
      efficacy of prolonged antibiotic therapy, often with relapse of the symptoms
      after discontinuation of therapy. To date, only one randomized, placebo
      controlled, double-blind trial of antibiotic therapy for these patients has been
      published. An abstract of a second placebo-controlled trial of antibiotic therapy
      in a smaller cohort has also been presented. This paper will describe this
      patient population in detail and will review the clinical, microbiological, and
      selected biochemical and immunologic parameters and their responses to antibiotic
      treatment in the setting of a controlled trial.

PMID- 12804168
TI  - Epidemiology and impact of coinfections acquired from Ixodes ticks.
AB  - Ixodes scapularis and other ticks in the Ixodes ricinus complex may transmit
      multiple pathogens, but research on coinfections has been limited. Coinfections
      occur with varying frequency in ticks, but single infections are more common than
      dual infections. The proportion of I. scapularis or I. ricinus ticks coinfected
      with both Borrelia burgdorferi sensu lato and Anaplasma phagocytophila is
      generally low, ranging from < 1% to 6% in six geographic areas. A higher
      prevalence of tick coinfection (26%) has been reported in Westchester County, New
      York. Genetic variants of the human disease-causing strain of A. phagocytophila
      are present in some tick populations, and they may affect the risk of coinfection
      or clinical illness. The proportion of Ixodes ticks coinfected with B.
      burgdorferi and Babesia microti has ranged from 2% in New Jersey to 19% on
      Nantucket Island, Massachusetts. In humans, cross-sectional seroprevalence
      studies have found markers of dual infection in 9-26% of patients with a tick
      borne infection, but such studies often fail to distinguish simultaneous
      coinfection from sequential infections. Several studies have prospectively
      assessed the occurrence of acute coinfection. Among patients with a confirmed
      tick-borne infection, coinfection rates as high as 39% have been reported. The
      most commonly recognized coinfection in most of the eastern United States is Lyme
      borreliosis (LB) and babesiosis, accounting for approximately 80% of
      coinfections. LB and human granulocytic ehrlichiosis coinfections are less
      common, occurring in 3-15% of patients with a tick-borne infection in Connecticut
      or Wisconsin. Studies of clinical outcomes suggest that patients with acute
      Babesia coinfection have more severe symptoms and a longer duration of illness
      than patients with LB alone, but the risk of spirochete dissemination is similar.
      Coinfections can modify the immune response and alter the severity of arthritis
      in animal models. Future coinfection research should focus on long-term clinical
      outcomes, the role of genetic variants, immunologic effects, and the potential
      role of Bartonella species as tick-borne pathogens.

PMID- 12804169
TI  - Toll-like receptor 2 plays a pivotal role in host defense and inflammatory
      response to Borrelia burgdorferi.

PMID- 12804170
TI  - Long-term outcomes of persons with Lyme disease.

PMID- 12804171
TI  - Successful stem cell mobilization with stem cell factor and granulocyte colony
      stimulating factor in patients with solid tumors failing conventional
      mobilization with chemotherapy and G-CSF.

PMID- 12804172
TI  - Response to "On the ethics of therapeutic cloning".

PMID- 12804173
TI  - The origin and development of the immune system with a view to stem cell therapy.
AB  - Careful study of the phylogeny and ontogeny of the three components of the immune
      system reveals that the macrophage, lymphatic, and hematopoietic systems
      originate independently of each other. Chronologically, the most ancient is the
      macrophage system, which arises in the coelomic cavity as mesenchymal ameboid
      cells having the properties to recognize self from non-self and to ingest foreign
      particles. The lymphatic system later develops from the endoderm of pharyngeal
      pouches, where the thymic anlage differentiates. The lymphocytes that originate
      here seed all lymphatic organs and retain the ability to divide and thereby form
      multiple colonies (lymphatic nodules) in the respiratory and digestive tract;
      further diversification of lymphocytes follows after confrontation with antigens.
      The last component of the immune system to appear is the hematopoietic system,
      which originates from the splanchnic mesoderm of the yolk sac as hematogenic
      tissue, containing hemangioblasts. The hematogenic tissue remains attached to the
      outer wall of the vitelline vessels, which provides an efficient mechanism for
      introducing the hematogenic tissue into the embryo. In an appropriate
      microenvironment, the hemangioblasts give rise to sinusoidal endothelium and to
      hemocytoblasts - the bone marrow stem cells for erythrocytes, myeloid cells, and
      megakaryocytes. The facts and opinions presented in this article are not in
      agreement with the currently accepted dogma that a common "hematolymphatic stem
      cell" localized in the marrow generates all of the cellular components of blood
      and the immune system.

PMID- 12804174
TI  - Infectious complications in patients receiving mobilization chemotherapy for
      autologous peripheral blood stem cell collection.
AB  - The purpose of this retrospective study was to evaluate infectious complications
      in patients receiving mobilization chemotherapy for stem cell collection prior to
      autologous peripheral blood stem cell transplantation. An additional goal was to
      evaluate risk factors associated with the development of infectious
      complications. At the Medical College of Georgia BMT center, 54 patients were
      administered mobilization chemotherapy for the purpose of collecting stem cells
      between June, 1997, and May, 2002. All patients received Filgrastim in addition
      to chemotherapy, and 50 of 54 patients received prophylactic acyclovir,
      fluconazole, and ciprofloxacin until neutrophil recovery. The median duration to
      neutrophil recovery was 11 days. Fourteen of 54 (26%) patients developed
      fever/infections during the mobilization phase. One patient developed both a
      catheter-related infection and Clostridium difficile colitis, increasing the
      total number of infectious episodes to 15. Twelve patients had a documented site
      of infection whereas 2 patients had neutropenic fever with no identifiable
      source. Eight of the 15 (55%) infections were Gram-positive catheter infections.
      All the patients were treated successfully with antibiotics. No systemic fungal
      infections were identified and none of the patients died from complications
      related to mobilization chemotherapy. Logistic regression was applied for
      univariate and multivariate analysis and showed that age, sex, diagnosis,
      neutrophil recovery, disease status, use of salvage chemotherapy, and
      mobilization regimen used did not affect the infection rate. In our series of 54
      patients, 14 patients developed fever/infections during mobilization. Although
      there is a substantial risk of infectious complications among patients who
      receive mobilization chemotherapy, it is not clear that prophylactic antibiotics
      decrease infectious complications. Because the vast majority of infections are
      Gram-positive catheter infections, it appears reasonable to employ Gram-positive
      prophylaxis. Controlled studies should be conducted to define the optimum
      mobilization regimens as well as the optimum combination of prophylactic
      antibiotics.

PMID- 12804175
TI  - The risk of infection transmission from blood progenitor cell concentrates.
AB  - The possibility of infection transmission by infusion of cryopreserved peripheral
      blood stem cells concentrates or bone marrow is well known. For this reason the
      European Blood and Marrow Transplantation Group (EBMT) and International Society
      for Haemotherapy and Graft Engineering (ISHAGE) standards include a panel of
      serological tests to be performed in donors and patients with the aim to lower
      the likelihood of infection transmission. The study was performed on a group of
      71 patients and 22 donors. No laboratory signs of active infection were found in
      15 donors (13 related, 2 unrelated), i.e., in 68.2% and in 55 patients (77.5%).
      The active infection from herpes viruses was the most common (in patients 13, in
      donors 7). Hepatitis B was found in only one case. The cytomegalovirus (CMV)
      immunoglobulin G (IgG) test was the most common marker of previous infection, and
      it was found in 14 donors and 55 patients. We can conclude that the rate of
      clinically unsuspected infections in donors and patients, including cases
      requiring immediate treatment among the patient groups, is relatively high and
      fully justifies the practice of prophylactic serological testing using the whole
      palette of tests according to EBMT and ISHGE in both autologous and allogenous
      transplantations of hematopoietic stem cells.

PMID- 12804176
TI  - Macrophage-stimulating protein cooperates with erythropoietin to induce colony
      formation and MAP kinase activation in primary erythroid progenitor cells.
AB  - We have shown that Fv2, the Friend virus susceptibility 2 locus, encodes a
      naturally occurring amino-terminally truncated form of the STK receptor tyrosine
      kinase (Sf-Stk). Sf-Stk appears to interact with the viral glycoprotein gp55 and
      drive erythropoietin (Epo)-independent expansion of Friend virus-infected
      erythroblasts. Presumably, Sf-Stk provides signals that cooperate with EpoR
      signaling to induce the polyclonal expansion of infected cells. In this report,
      we show that macrophage-stimulating protein (MSP), the ligand for full-length
      STK, can also cooperate with Epo to enhance burst-forming units-erythroid (BFU-E)
      formation. To evaluate the signals induced by MSP/STK in primary erythroid
      progenitor cells, we adapted a method for the expansion of murine bone marrow
      mononuclear cells. The expanded progenitor cells express STK and respond to MSP
      in a colony assay. Furthermore, we demonstrate that low doses of MSP and Epo
      stimulation of the expanded cells cooperate to induce the phosphorylation of MAP
      kinase. Using the MEK inhibitor PD98059, we show that the activation of ERK is
      required for the enhanced BFU-E formation in response to MSP. These findings
      suggest that MSP has the ability to enhance erythroid colony formation in
      response to Epo, and that this response is dependent on the ability of MSP to
      induce the MAP kinase pathway.

PMID- 12804177
TI  - Preferential ex vivo expansion of megakaryocytes from human cord blood CD34+
      enriched cells in the presence of thrombopoietin and limiting amounts of stem
      cell factor and Flt-3 ligand.
AB  - The high proliferative potential of cord blood (CB) stem cells and the
      identification of the key factor of megakaryopoiesis, thrombopoietin (TPO),
      permit the ex vivo expansion of megakaryocytes (MKs) for possible use in early
      post-transplant support of patients and the production of functional platelets
      for transfusion. However, culture conditions for the generation of adequate MKs
      for this purpose are not yet optimized. Therefore, we sought to define the
      mixture of early-acting cytokines and TPO that would promote the expansion of MK
      progenitors over other lineages and result in overall better MK expansion and
      platelet yields. CB CD34(+)-enriched cells were cultured in serum-free medium for
      17 days in presence of TPO alone or in various combinations with early-acting
      cytokines used at different concentrations and addition times. MK expansion and
      polyploidy and platelet production were monitored by flow cytometry analysis
      using specific surface markers (CD41 and CD42b) and propidium iodide labeling.
      Our results showed that the use of high concentrations of stem cell factor (SCF)
      and Flt-3 ligand (FL) in early CB TPO-supplemented cultures was more favorable to
      monocytic and granulocytic cell expansion. However, we observed that their
      presence in limiting amounts was required for the preferential expansion of MK
      progenitors. The addition of SCF, FL, TPO, and interleukin-6 (IL-6) at high
      concentrations in secondary cultures of these expanded MKs resulted in optimal MK
      proportion (approximately 25% of MKs) and expansion (>300 MK per seeded cell),
      highest proportions of polyploid MKs (22% of mature MKs > or = 8N), and best
      platelet yields. Our results indicate that TPO-induced MK progenitors are more
      sensitive to early-acting cytokines than non-MK cells. We propose that MKs
      generated in the optimized conditions, in combination with immature
      stem/progenitor cells, could prove useful for the short-term platelet recovery
      following CB transplantation.

PMID- 12804178
TI  - Phenotypic and immunologic characteristics of docetaxel-mobilized peripheral
      blood stem cells in mice.
AB  - Effective mobilization of peripheral blood stem cells is vital for
      transplantation of patients after high-dose chemotherapy and provides a
      convenient source of stem cells for genetic engineering and other studies, but
      optimal mobilization strategies have not been defined. Recent studies show that
      in the presence of recombinant human granulocyte colony-stimulating factor (rhG
      CSF), docetaxel (DXT) is an effective mobilization agent. This study was
      performed to evaluate the phenotype and immunologic properties of DXT-mobilized
      stem cells. Administration of DXT + rhG-CSF to normal C57Bl/6 mice induced a 75
      fold increase in blood hematopoietic progenitors and a significant increase in
      both CD3(+) (T cell) and DX5(+) [natural killer (NK)] cells when compared to
      untreated mice. The cytotoxicity of DXT + rhG-CSF-mobilized cell populations
      against YAC-1 and B16F10 cell lines was not significantly different from that of
      untreated mice. When compared to cyclophosphamide + rhG-CSF, DXT + rhG-CSF
      mobilized cell populations yielded a greater number of T and NK cells, with
      significantly higher cytotoxic effector function. These results suggest that DXT
      + rhG-CSF-mobilized PBSCs retain potent immunologic capacity with a high number
      of the functional cellular subsets than those normally present in peripheral
      blood, which may be important in maintaining the antitumor immunity after
      transplantation.

PMID- 12804179
TI  - Characterization of multiple CD34+ cell populations in cord blood.
AB  - Unlike granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood,
      which show a single homogeneous population of CD34(+) cells, umbilical cord blood
      (CB) CD34(+) cells are present as multiple populations, CD34(regular) and
      CD34(bright) (the latter comprising 7.0-58.2% of the total CD34(+) cells), using
      the ProCOUNT trade mark procedure or with anti-CD34 labeling of immunoselected
      cells. The CD34(regular) population contains cells with high forward scatter
      (CD34(regular)FSC(high)) and with low forward scatter (CD34(regular) FSC(low)).
      Immunomagnetically selected CD34(+) cells, sorted into CD34(regular),
      CD34(regular) FSC(high), CD34(regular)FSC(low), and CD34(bright) cell
      populations, were used in in vitro assays: only the CD34(regular)FSC(high)
      population transmigrated and showed growth of colony-forming unit (CFU) and long
      term culture initiating cells (LTC-IC) colonies. The absolute number of CD34(+)
      cells in CB samples was determined by ProCOUNT trade mark and Stem Kit trade mark
      enumeration protocols. In liquid stored CB units, ProCOUNT trade mark and Stem
      Kit trade mark count differences are accounted for by the enumeration of
      CD34(bright) cells. Differences between ProCOUNT trade mark and Stem Kit trade
      mark counts using cryopreserved/thawed samples are accounted for by increased
      CD34(regular) FSC(low) cell numbers (2.0 +/- 1.4% in liquid stored and 27.8 +/-
      14.6% in cryopreserved/thawed samples). The ProCOUNT trade mark assay includes
      the nonfunctional CD34(bright) and CD34(regular)FSC(low) cells as part of the
      CD34(+) cell count, thereby elevating the absolute number of CD34(+) cells. Using
      the Stem Kit trade mark assay method of gating, CD34(bright) and
      CD34(regular)FSC(low) cells are not counted. Our data indicate that the
      CD34(regular)FSC(high) cell population has functional characteristics based on
      the in vitro assays and a more accurate count of these cells can be achieved
      using the Stem Kit trade mark assay.

PMID- 12804180
TI  - Homocysteine and prothrombin fragment 1+2 levels in patients with veno-occlusive
      disease after stem cell transplantation.
AB  - Veno-occlusive disease (VOD) of the liver remains a major complication after
      hematopoietic stem cell transplantation (SCT). VOD is thought to develop after
      hepatic endothelial cells are damaged by high-dose chemotherapy or radiation,
      causing microthrombosis in hepatic venules. However, the precise mechanisms
      leading to VOD are not well defined, and a diagnosis is often difficult to
      establish. It is also difficult to predict which patients are most likely to
      develop VOD. Elevated levels of homocysteine (HC) have been associated with
      thrombosis, and prothrombin fragment 1 + 2 (F1 + 2) is a measurable marker for
      coagulation. Therefore, we performed a prospective cohort study to determine if
      HC or F1 + 2 levels could be used to predict the development of VOD prior to SCT,
      or to help establish a diagnosis of VOD in association with other clinical
      parameters. Plasma levels of these factors were measured before conditioning and
      serially for 21 days after SCT in 42 consecutive patients undergoing SCT. Eleven
      of 26 allogeneic SCT recipients developed VOD, whereas no autologous SCT
      recipient (n = 16) developed VOD (p = 0.008). In patients who developed VOD, HC
      levels were consistently higher than those seen in non-VOD patients after day 7
      of SCT. Patients with VOD also had higher levels of F1 + 2 after SCT, although
      this marker was less consistently elevated over time. A logistic regression model
      that evaluated all serial measures of HC and F1 + 2 showed a moderate sensitivity
      and specificity in diagnosing VOD in allogeneic SCT patients, but neither marker
      was useful to predict development of VOD when tested prior to SCT.

PMID- 12804181
TI  - Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells.
AB  - BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian
      myeloblastosis virus. The constitutively high v-myb expression interferes with
      the terminal differentiation of BM2 cells, but these cells can be induced to
      differentiate into macrophage-like cells by phorbol esters. Histone acetylation
      plays an important role in regulation of transcription and is particularly
      relevant to the regulation and pathology of hematopoiesis. In the present study,
      we examined the contribution of elevated histone acetylation to the
      differentiation of BM2 cells. Inhibition of the activity of endogenous histone
      deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing
      cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons.
      TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated
      its transcription activation capability. This suggests that chromatin remodeling
      can be significantly engaged in regulation of proliferation and differentiation
      of leukemic cells.

PMID- 12804183
TI  - An in vitro model for grafting of hematopoietic stem cells predicts bone marrow
      reconstitution of myeloablative mice.
AB  - Homing and engraftment of hematopoietic stem cells (HSCs) to bone marrow (BM) is
      a complex process that primarily depends on the cell-surface expression of
      adhesion molecules on stem and stromal cells. Here we report an in vitro model
      for homing of stem cells on pre-established stromal layer; the stroma-adhered
      cells were found to engraft, multiply, and differentiate in BM of age-matched
      mice. In vitro study revealed that initially the adhesion of BM cells on
      irradiated stroma was increased with time, and it attained a peak at 2 h of
      contacts. During that time, 44.1 +/- 6.5% (n = 8) cells were adhered, and this
      value was maintained up to 6 x 10(6) cells. The adhered cell fraction was
      enriched by 3.9-, 2.5-, and 1.7-fold Sca-1, colony forming cell (CFC), and
      cobblestone area forming cells (CAFC), respectively, as compared to the fresh BM
      cells. These adhered cells homed to BM with an engraftment efficiency of 11.8 +/-
      2.5% (n = 6). The homed cells reconstituted BM of myeloablative mice by self
      renewing and differentiating into myeloid cells. Overall, a simple in vitro model
      system has been described to study homing and grafting of HSCs that can be
      deployed to any possible experimental conditions to investigate the interactions
      between stromal and stem cells.

PMID- 12804182
TI  - Influence of anti-thymocyte globulin as part of the conditioning regimen on
      immune reconstitution following matched related bone marrow transplantation.
AB  - The aim of this work was to analyze the influence of anti-thymocyte globulin
      (ATG) as part of the conditioning regimen on immune reconstitution following
      matched related bone marrow transplantation. The rate and pattern of the recovery
      of total lymphocytes, natural killer (NK) cells, and several T and B cell subsets
      were determined in 38 patients for more than 2 years following BMT. We compared
      two patient groups: the first comprised 19 patients after matched related BMT
      without ATG prevention for graft-versus-host disease (GVHD) and the second
      contained 19 patients after matched related BMT with ATG treatment for GVHD
      prophylaxis. We observed impaired immune reconstitution in the ATG group in
      comparison with the non-ATG group, indicating a significant influence of ATG on
      immune recovery for several months after BMT.

PMID- 12804184
TI  - Ethical issues and the commercialization of embryo culture media.

PMID- 12804185
TI  - Designer babies - are they a reality yet?

PMID- 12804186
TI  - Adolescent sexual and reproductive health.
AB  - This paper assesses how young people and adolescents are defined within each
      country according to its laws and policies. Additionally, the reproductive health
      situation of adolescents varies with gender and age. Age of onset of intercourse,
      age of marriage and child bearing, use of contraception, and the status of women
      in society all vary with country and region of the world. These variations have
      direct implications for the population's reproductive health, with potential
      consequences leading to disability, infertility, sexual violence and abuse, and
      even death. Nutritional status, access to educational opportunities, access to
      reproductive health services and commodities, and some life style behaviours such
      as alcohol, tobacco and other drug abuse, may all have an impact on the future
      reproductive health of the current and the next generations.

PMID- 12804187
TI  - Heparin binding-epidermal growth factor improves blastocyst hatching and
      trophoblast outgrowth in the golden hamster.
AB  - The effect of heparin binding-epidermal growth factor (HB-EGF) on the in-vitro
      development of hamster 8-cell embryos was investigated. Supplementation of HB-EGF
      to culture medium accelerated zona escape of blastocysts (63 +/- 9% compared with
      33 +/- 9% after 36 h; P < 0.05). Complete zona escape of blastocysts persisted
      even after 48 h (61 +/- 11% versus 30 +/- 4%) and 60 h (75 +/- 6% versus 42 +/-
      8%). Addition of anti-HB-EGF antibody drastically reduced the percentage of zona
      escaped-blastocysts (30.0 +/- 5.0% versus 92.3 +/- 2.8%; P < 0.05).
      Interestingly, a significant increase in the area of trophoblast outgrowth
      occurred in the presence of HB-EGF (116 x 10(3) +/- 8 x 10(3) microm(2) versus 74
      x 10(3) +/- 8 x 10(3) microm(2) at 48 h; P < 0.05). This, however, was not due to
      an increased number of trophectodermal cells in HB-EGF-treated blastocysts.
      Immunoreactive HB-EGF was localized in blastocysts and uterine sections, visible
      by intense immunostaining in the luminal epithelium, particularly on the apical
      surface. Moreover, the expression of HB-EGF in the uterus was maximum on day 4 of
      pregnancy, coinciding with the timing of zona escape and implantation. The
      receptor of HB-EGF, viz. EGF receptor was also detected in blastocysts and the
      luminal epithelium of day 4 pregnant uterus. These results show that HB-EGF
      improves blastocyst hatching and trophoblast outgrowth in hamsters.

PMID- 12804188
TI  - Mitochondrial DNA point mutation in human oocytes is associated with maternal
      age.
AB  - Mitochondrial DNA (mtDNA) point mutations are known to accumulate in an age
      dependent fashion in somatic tissues. This study investigated whether a point
      mutation (T414G) in the mtDNA control region was present in oocytes from women of
      advanced age. In all, 66 non-viable discarded human oocytes were analysed for the
      presence of a T414G transversion mutation. DNA sequence analysis confirmed the
      presence of this mutation in one oocyte from 11 patients between the ages of 26
      and 36 years (n = 23), compared to 17 oocytes from 10 patients between the ages
      of 37 and 42 years (n = 43). The younger group exhibited this mtDNA point
      mutation in only 4.4% of oocytes compared to 39.5% from the older group (P <
      0.01). Therefore, single human oocytes contain the mtDNA T414G transversion point
      mutation that accumulates in an age-dependent manner. The potential significance
      of this point mutation may be its association with reproductive senescence.
      Furthermore, since this mutation exists in the control region of the mtDNA it may
      affect the regulation of mtDNA transcription and replication during oocyte and
      post-embryonic development.

PMID- 12804189
TI  - One hundred and three concurrent IVF successes for donors and recipients who
      shared eggs: ethical and practical benefits of egg sharing to society.
AB  - Egg sharing is a form of egg donation where complete strangers can collaborate
      anonymously to overcome their involuntary childlessness. In a retrospective
      analysis, results of egg sharing treatments were analysed in 37 consecutive
      donors and 39 recipients who had achieved concurrent success following IVF
      treatment. The interval between being accepted onto the programme and receiving
      treatment was less than 6 months for most patients. Births of 103 infants are
      expected. Multiple pregnancy rates were high and equivalent in both the groups
      (donors 32.4%, recipients 25.6%) despite the original number of eggs available
      being halved at egg collection and equal numbers being allocated to donors and
      recipients. On average fewer than six eggs were required for the birth of each
      baby. More successes are expected in time as 33 couples (43.4%) have their excess
      embryos stored for future use. The programme avoided the need to advertise for
      donors. This had particular significance for members of minority ethnic groups.
      It is surmised that promotion of concurrent treatment of egg sharers and
      recipients will attract funds from insurance providers or health boards who are
      unimpressed by IVF treatments with indifferent success rates and runaway costs.
      In the event of such funds materializing, meagre NHS resources for IVF treatment
      could be better focused. Overall, the benefit derived from applying the
      simultaneous treatment of anonymous donors and recipients is so compelling as to
      make it the preferred IVF option for qualifying couples.

PMID- 12804190
TI  - Design, beauty and differentiation: the human fetus during the first trimester of
      gestation.

PMID- 12804191
TI  - Introduction to anatomy and physiology of human conception.
AB  - Anatomical and physiological concepts of human reproduction currently in use have
      been developed over generations, following clinical and basic research guidelines
      that preceded modern technology. The application of new forms of research over
      recent decades, as in the case of molecular biology, has contributed to a more in
      depth and accurate understanding of the interaction of each of the inter- and
      intracellular structures in the mechanics of human physiology. On the other hand
      the use of non-human primate models has provided invaluable information in the
      reproductive field. The information obtained through models and techniques that
      have changed over time has led to concepts that continue to have the same
      validity as when they were first described. The principal objective of this
      review is to develop an understanding of the physiological processes applied in
      the anatomical sphere, taking as a reference the fact that it is impossible to
      understand reproductive mechanics in terms of static phenomena, but rather they
      should be understood as dynamic and changing processes adaptable to the
      conditions of each individual's surroundings.

PMID- 12804192
TI  - Human menopause delay.

PMID- 12804193
TI  - Exciting times for gene knockout and homologous recombination.

PMID- 12804195
TI  - A well-taken opportunity for double blessing.

PMID- 12804194
TI  - Designer babies - are they a reality yet? Case report: simultaneous
      preimplantation genetic diagnosis for Fanconi anaemia and HLA typing for cord
      blood transplantation.

PMID- 12804196
TI  - Severe haemophilia following use of donor eggs: implications for screening of
      prospective donors.
AB  - Oocyte donation has become a common treatment modality for a range of infertility
      conditions. The Shared Egg Donation (SED) scheme is one of various strategies
      that now exist to try and overcome shortages, that have invariably occurred from
      the very success of oocyte donation procedures. Despite a reassuring positive
      profile that has been demonstrated, some residual concerns still exist with
      regard to the SED programme. We report the first case of severe haemophilia
      following use of donor eggs in the SED scheme. The case has not only illustrated
      potential problems that can occur with egg donation schemes, but also suggested a
      plausible model on which to base future management of similar cases. The case
      furthermore illustrates that there is no substitute for 'good practice' in
      ensuring those risks and concerns of egg donation programmes are kept to
      acceptable limits.

PMID- 12804197
TI  - Blood biochemistry and endocrinology in the human fetus between 11 and 17 weeks
      of gestation.
AB  - Fetal blood was obtained in 35 normal pregnancies undergoing termination for
      psychosocial reasons between 11 and 17 weeks of gestation. Biochemical and
      endocrinological analyses were performed on each sample including concentrations
      of urea, creatinine, beta-microglobulin total protein, electrolytes, enzymes,
      alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG), thyroid stimulating
      hormone (TSH), thyroxin binding globulin (TBG), total thyroxin (TT4) and free
      thyroxin (FT4). The results were compared with values in maternal serum obtained
      at the same time. Fetal serum contained significantly higher concentrations of
      iron, beta-microglobulin, alkaline phosphatase (ALP), aspartate amniotransferase
      (AST), AFP, HCG and TSH and lower concentration of total protein, TBG and TT4
      than maternal serum. Significant positive linear relationships were found between
      gestational age and the concentration of fetal serum total protein, ALP, TBG and
      FT4. Significant negative linear relationships were observed between gestational
      age and fetal serum beta-microglobulin and iron concentration. There were no
      significant correlations between fetal and maternal values. These data indicate
      that fetal blood biochemistry is not directly related to placental transfer and
      that the proteins and enzymes found inside the gestational sac are essentially of
      feto-placental origin with minimal contribution from the maternal protein
      metabolism. The comparison of coelomic fluid composition at 10-13 weeks with that
      of fetal serum at 11-17 weeks suggests that the anatomical changes in the human
      materno-fetal interface architecture between the early and late pregnancy periods
      could have a direct impact on materno-fetal transfer pathways.

PMID- 12804198
TI  - Preimplantation diagnosis for ornithine transcarbamylase deficiency.
AB  - Ornithine transcarbamylase (OTC) deficiency is a severe X-linked metabolic
      disorder leading to hyperammonaemia and death shortly after birth. Prenatal
      diagnosis for OTC deficiency is available, but may require termination of
      pregnancy if affected. Thus there is a need for an option for pre-pregnancy
      testing, to pre-select OTC deficiency-free embryos for transfer, thus avoiding
      prenatal diagnosis and pregnancy termination. Preimplantation genetic diagnosis
      (PGD) for OTC deficiency has been developed, using sequential first and second
      polar body analysis; it was applied in a woman carrying the R26Q mutation in the
      exon 1 of OTC gene. The first and second polar bodies were removed following
      maturation and fertilization of oocytes in a standard IVF protocol, and analysed
      using a multiplex nested PCR. R26Q mutation was tested simultaneously with linked
      markers in six zygotes, resulting in detection of the embryos with a mutation
      free maternal contribution; these were transferred back to the patient, yielding
      pregnancy and birth of a healthy child. This is the first PGD for OTC deficiency
      resulting in the birth of an unaffected child.

PMID- 12804201
TI  - Summaries for students, patients and lay readers.

PMID- 12804199
TI  - Biochemical and functional aspects of gonadotrophin-releasing hormone and
      gonadotrophins.
AB  - Reproductive function in mammals is governed by the hypothalamic-pituitary
      gonadal axis, which conforms a functional unit. Sexual maturation and the
      subsequent development of reproductive competence depend on the precise and
      coordinated function of this axis. The components of the reproductive axis
      communicate each other through endocrine signals. The hypothalamus synthesizes
      gonadotrophin-releasing hormone or GnRH, which in turn stimulates synthesis and
      secretion of the pituitary gonadotrophins, follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH). The ovarian follicles and the interstitial and Sertoli
      cells of the testis are the targets for these pituitary signals. Under
      gonadotrophic stimulation, the gonads produce and secrete several steroid and non
      steroid (polypeptide) factors, which in turn regulate in different ways the
      function of the hypothalamic-pituitary axis. An episodic and pulsatile mode of
      secretion of hormonal signals characterize (as in other endocrine systems) the
      function of the reproductive axis, particularly that of the hypothalamic
      pituitary unit. The target cell response, and consequently the harmonic function
      of the corresponding gland, will depend on the adequate dynamics of this
      pulsatile secretion. The function of each component of the reproductive axis is
      strongly influenced by locally-produced signals acting either in a paracrine or
      autocrine manner; these particular signals represent fine-tuning regulation
      systems that eventually amplify or restrain the magnitude of response to a
      particular endocrine signal, providing additional mechanisms for tissue
      homeostasis and a better functional plasticity of the target gland. The design
      and rational use of novel therapeutic strategies for an optimal exogenously
      controlled reproductive function largely depend on the detailed knowledge of the
      hypothalamic-pituitary-gonadal axis function and the structure and mechanism of
      action of those factors and signals involved in its regulation.

PMID- 12804202
TI  - Reproductive health of women in developing countries.

PMID- 12804204
TI  - Summaries for students, patients and lay readers.

PMID- 12804203
TI  - Medical ethics in the melting pot: still strict for IVF but possibly soon also
      for other clinical disciplines.

PMID- 12804206
TI  - Medical management of male infertility.
AB  - The medical management of male infertility has a precise role to play.
      Inappropriate use of drugs, apart from not promoting fertility, may actually
      predispose to infertility. Gonadotoxic or gametotoxic drugs should be avoided if
      possible. If potentially toxic drugs are used for a medical condition, suitable,
      less or non-toxic alternatives should be used. Where medical management is not
      possible, instead of wasting time and money on expensive unproven therapies,
      early recourse to assisted reproduction must be sought.

PMID- 12804207
TI  - Chromosome abnormalities in 1255 cleavage-stage human embryos.
AB  - The relationship was examined between chromosome abnormalities in cleavage stage
      human embryos and maternal age, embryo morphology and development rate. Embryos
      that were classified as suboptimal for transfer from patients undergoing IVF
      treatment were disaggregated, and all or most of their cells were fixed for
      analysis by fluorescence in-situ hybridization. Chromosomes X, Y, 13, 18 and 21,
      and in some instances 16 were examined. A total of 731 non-viable embryos was
      analysed. An increase in chromosome abnormalities with decreasing embryo
      competence and increasing maternal age was shown. Compared with an earlier study,
      the major difference was that polyploidy (P<00.01) and aneuploidy were previously
      more common. After pooling results, it was found that aneuploidy increased with
      maternal age, from 3.1% in embryos from 20-34 years old patients to 17% in
      patients 40 years or older. Also, aneuploidy occurred more frequently in embryos
      with good morphology and development rate than in embryos developing poorly. In
      contrast, dysmorphic and slowly developing or arrested embryos had significantly
      more polyploidy and mosaicism than normally developing embryos. Clear
      associations between maternal age and aneuploidy, and between cleavage anomalies
      and mosaicism have been established in non-viable embryos. Arrested embryos were
      mostly polyploid. Moreover, polyploidy was found more frequently in embryos
      analysed on day 4, suggesting that developmentally compromised embryos became
      arrested in extended culture. A slightly higher aneuploidy rate in the earlier
      study may be attributed to differences in hormonal stimulation, which also
      resulted in different numbers of oocytes recruited and matured.

PMID- 12804208
TI  - Is the aged rat ear more susceptible to noise or styrene damage than the young
      ear?
AB  - Noise- and styrene-induced hearing and hair cell loss were studied in young (3
      months) and aged (24-26 months) Long-Evans rats. The animals were exposed 6 h/d,
      5 d/w for 4 weeks to (a) broadband noise centered at 8 kHz (92 or 97dB SPL), or
      b) styrene (700 ppm). Auditory sensitivity was tested by recording evoked
      potentials from the inferior colliculus. Histological analyses of the organ of
      Corti, stria vascularis, and the spiral ganglions were also performed. Aged
      controls showed outer hair cell (OHC) loss at the basal and apical regions of the
      organ of Corti, and an increase in pigmentation concomitant to a decrease in
      vascularization of the stria vascularis, along with elevated thresholds relative
      to young controls. The 92-dB noise caused similar threshold shifts in both age
      groups, whereas the 97-dB noise caused more threshold shifts in the aged group
      compared to the young group. Recovery of the hearing thresholds depended both on
      the intensity of the noise and on the age of the animals. Aged rats had minimal
      hair cell loss as a result of styrene exposure, whereas young animals showed
      significant OHC loss, particularly in third row. Despite significant loss of
      OHCs, the young subjects showed styrene-induced threshold shifts only at high
      frequencies. In summary, the data show that : (a) there is an influence of age on
      both noise-induced and styrene-induced threshold shift and hair cell loss in rats
      and (b) the cochlea appear to have a redundancy in the number of OHCs, thus
      threshold shift does not necessarily occur with significant OHC loss.

PMID- 12804209
TI  - Qualitative responses of children to environmental noise.
AB  - Results from recent quantitative research consistently demonstrate that children
      are a high risk group, vulnerable to the adverse effects of noise exposure,
      especially effects on cognitive performance, motivation and annoyance. The aims
      of the two qualitative studies reported in this paper are to explore children's
      a) perception of noise exposure; b) perceived risk of and attitudes towards noise
      pollution; c) coping strategies; and d) the annoyance response. The Millennium
      Conference Study involved focus group interviews with an international sample
      (n=36) unselected by exposure. The West London Schools Study involved individual
      interviews, conducted with a purposively selected sample (n=18) exposed to
      aircraft noise. The children in the focus groups reported being most affected by
      neighbours' noise and road traffic noise, whereas children exposed to aircraft
      noise were most affected by aircraft noise. As expected, the impact of noise
      pollution on everyday activities (e.g. schoolwork, homework and playing) was
      larger for the children exposed to high levels of aircraft noise compared with
      the low noise exposed children and focus group samples. The range of coping
      strategies that children employed to combat noise exposure in their lives was
      dependent upon the amount of control they had over the noise source. The
      emotional response of children describing the annoyance reaction to noise was
      consistent with adult reactions and it would seem that child noise annoyance is
      the same construct. Future research should employ qualitative methods to
      supplement quantitative investigations.

PMID- 12804210
TI  - The effects of chronic aircraft noise exposure on children's cognition and
      health: 3 field studies.
AB  - This article provides a review of three of the most important field studies to
      have examined the non-auditory effects of chronic aircraft noise exposure on
      children's cognition and health. The design of each of the studies is outlined,
      relevant methodological issues are highlighted and the findings from the studies
      are reported. Effects are reported on annoyance and quality of life, motivation
      and helplessness, stress responses as indexed by neuroendocrine tests and blood
      pressure measurements. In terms of cognitive performance, effects are reported on
      reading, attention and long-term and working memory.

PMID- 12804211
TI  - Respiratory and dermatological diseases in children with long-term exposure to
      road traffic immissions.
AB  - The pathogenesis of allergies can be stimulated by adjuvant effects--i.e. air
      pollutants such as NO(2) and particles from diesel exhausts as well as noise--the
      latter especially during night-time. During sleep, noise signals which are
      associated with danger (i.e. lorry noise) have the potential to trigger stress
      reactions even if the noise level is low. Increases of cortisol in the first half
      of the night seem to play an important role. In a blind interview study, the
      combined effects of chronic exposure to traffic related air pollution and noise,
      upon the risk of skin and respiratory diseases in children were studied. All
      children between 5-12 years, who had consulted one of two participating
      paediatricians were included in the study. The paediatricians diagnoses of 400
      children were analysed together with their parents answers regarding the density
      of road traffic on their street and several confounding factors. Multiple
      regression analyses resulted in relative risks of asthma, chronic bronchitis and
      neurodermitis, which increased significantly with increasing traffic load. A
      comparison with the literature on such effects caused by air pollution alone,
      showed that traffic noise during the night might have an adjuvant effect on the
      pathogenesis of the mentioned diseases.

PMID- 12804212
TI  - The sound exposure of the audience at a music festival.
AB  - During the Paleo Festival in Nyon, Switzerland, which took place from 24th to
      29th July 2001, ten volunteers were equipped each evening with small sound level
      meters which continuously monitored their sound exposure as they circulated among
      the various festival events. Sound levels at the mixing console and at the place
      where people are most heavily exposed (in front of the speakers) were measured
      simultaneously. In addition, a sample of 601 people from the audience were
      interviewed over the six days of the festival and asked their opinion of sound
      level and quality, as well as provide details of where in the arena they
      preferred to listen to the concerts, whether they used ear plugs, if they had
      experienced any tinnitus, and if so how long it had persisted. The individual
      sound exposure during a typical evening was on average 95 dB(A) although 8% of
      the volunteers were exposed to sound levels higher then 100 dB(A). Only 5% of the
      audience wore ear plugs throughout the concert while 34% used them occasionally.
      While some 36% of the people interviewed reported that they had experienced
      tinnitus after listening to loud music, the majority found both the music quality
      and the sound level good. The sound level limit of 100 dB(A) at the place where
      the people are most heavily exposed seems to be a good compromise between the
      public heath issue, the demands of artists and organisers, and the expectations
      of the public. However, considering the average sound levels to which the public
      are exposed during a single evening, it is recommended that ear plugs be used by
      concert-goers who attend more than one day of the festival.

PMID- 12804213
TI  - Prevention of adverse effects of noise on children.
AB  - This article presents findings from a European project co-ordinated by the
      National Institute of Public Health, Denmark. The project "Children and noise-
      prevention of adverse effects" was partly financed by the European Commission
      Programme on Pollution-related Diseases and included partners or consultants from
      six European Union Member States: Denmark, Germany, Italy, the Netherlands,
      Sweden and the United Kingdom. The project used a definition of noise based on
      children's special development and provides examples of good practice on how to
      prevent the harmful effects of noise in children's daily settings. The settings
      analysed were day-care centres, primary schools and discotheques. Two methods
      were applied to obtain the effective examples of noise prevention or noise
      reduction: reviewing existing research and interviewing key people with knowledge
      and experience that has not yet appeared in the literature. A range of cases of
      preventing the adverse effects of noise assessed before and after the
      intervention provide a number of good practices, including information and
      awareness-raising campaigns and the identification of key concepts and key
      players in the prevention of noise. The examples of good practice have been
      effective in reducing noise, reducing the effects of noise, increasing the
      awareness of the importance of noise reduction or increasing action to reduce
      noise. The examples are based on a common format for reviewing preventive
      measures and can serve as direct inspiration for action to prevent noise in
      children's daily settings.

PMID- 12804214
TI  - The International Network on Children's Health, Environment and Safety (INCHES).

PMID- 12804215
TI  - Policy Interpretation Network on Children's Health and Environment (PINCHE).

PMID- 12804216
TI  - Observations of noise exposure through the use of headphones by radio announcers.
AB  - This study examined the potential risk of hearing loss by commercial radio
      announcers. This risk is developed through the regular use of headphones. These
      headphones are used to monitor broadcast transmission and communication
      information from program producers. To our knowledge there are no published
      studies of the noise exposure of radio announcers. The experimental method
      utilised a headphone parallel to the one in use mounted on a wideband, artificial
      ear. A Sound Level Meter was then used to measure the sound level and then
      calculate the exposure level. Depending on the feedback level applied to their
      headphones radio announcers are exposed to potentially damaging levels of noise.
      Levels measured correlate with results from other studies of long-term average
      speech spectrum and voice level measurements.

PMID- 12804217
TI  - Large-scale simulations of concentrated emulsion flows.
AB  - Applications of the newly developed hybrid of the boundary integral and
      economical multipole techniques to large-scale dynamical simulations of
      concentrated emulsion flows of deformable drops are considered. For N = O(10(2)
      10(3)) drops in a periodic cell with O(10(3)) boundary elements per drop, the
      method has two to three orders of magnitude gain over a standard boundary
      integral method at each time-step, thus making long-time large-scale dynamical
      simulations feasible. In the steady shear flow, large systems N >/= O(10(2)) are
      imperative for convergence at high drop volume fractions c >/= 0.5. At high
      concentrations, most of the shear thinning occurs for nearly non-deformed drops;
      at c approximately 0.55 and small capillary numbers, phase transition is observed
      in dynamical simulations. In sedimentation of deformable drops from a homogeneous
      initial state, even larger N >/= O(10(3)) are required to accurately describe the
      Koch-Shaqfeh type of instability in a wide time range with N up to 1200 and
      ensemble averaging over the initial conditions. The dynamics of the average
      sedimentation rate is studied versus concentration c for matching viscosities
      lambda = 1; for a Bond number of 1.75, systems with c approximately 0.25 are
      found to be most unstable. Additionally, a low drop-to-medium-viscosity ratio
      system, lambda = 0.1, is more unstable than those with lambda = 0.25 and lambda =
      1. In the third application, buoyancy- or gravity-driven motion of a large
      bubble/drop through a concentrated emulsion of neutrally buoyant drops is studied
      by simulations. For a size ratio of two, convergent (box-size independent)
      results for the bubble/drop settling velocity are obtained in simulations with N
      </= 800.

PMID- 12804218
TI  - Film flow of a suspension down an inclined plane.
AB  - A method is developed for simulating the film flow of a suspension of rigid
      particles with arbitrary shapes down an inclined plane in the limit of vanishing
      Reynolds number. The problem is formulated in terms of a system of integral
      equations of the first and second kind for the free-surface velocity and the
      traction distribution along the particle surfaces involving the a priori unknown
      particle linear velocity of translation and angular velocity of rotation about
      designated centres. The problem statement is completed by introducing scalar
      constraints that specify the force and torque exerted on the individual
      particles. A boundary-element method is implemented for solving the governing
      equations for the case of a two-dimensional periodic suspension. The system of
      linear equations arising from numerical discretization is solved using a
      preconditioner based on a particle-cluster iterative method recently developed by
      Pozrikidis (2000 Engng Analysis Bound. Elem. 25, 19-30). Numerical investigations
      show that the generalized minimal residual (GMRES) method with this
      preconditioner is significantly more efficient than the plain GMRES method used
      routinely in boundary-element implementations. Extensive numerical simulations
      for solitary particles and random suspensions illustrate the effect of the
      particle shape, size and aspect ratio in semi-finite shear flow, and the effect
      of free-surface deformability in film flow.

PMID- 12804219
TI  - Solid-solid contacts due to surface roughness and their effects on suspension
      behaviour.
AB  - Solid-solid contacts due to microscopic surface roughness in viscous fluids were
      examined by observing the translational and rotational behaviours of a suspended
      sphere falling past a lighter sphere or down an inclined surface. In both cases,
      a roll-slip behaviour was observed, with the gravitational forces balanced by not
      only hydrodynamic forces but also normal and tangential solid-solid contact
      forces. Moreover, the nominal separation between the surfaces due to microscopic
      surface roughness elements is not constant but instead varies due to multiple
      roughness scales. By inverting the system, so that the heavy sphere fell away
      from the lighter sphere or the plane, it was found that the average nominal
      separation increases with increasing angle of inclination of the plane or the
      surface of the lighter sphere from horizontal; the larger asperities lift the
      sphere up from the opposing surface and then gravity at large angles of
      inclination is too weak to pull the sphere back down to the opposing surface
      before another large asperity is encountered. The existence of microscopic
      surface roughness and solid-solid contacts is shown to modify the rheological
      properties of suspensions. For example, the presence of compressive, but not
      tensile, contact forces removes the reversibility of sphere-sphere interactions
      and breaks the symmetry of the particle trajectories. As a result, suspensions of
      rough spheres exhibit normal stress differences that are absent for smooth
      spheres. For the conditions studied, surface roughness reduces the effective
      viscosity of a suspension by limiting the lubrication resistance during near
      contact motion, and it also modifies the suspension microstructure and
      hydrodynamic diffusivity.

PMID- 12804220
TI  - Film depth and concentration banding in free-surface Couette flow of a
      suspension.
AB  - The film depth of a free-surface suspension flowing in a partially filled
      horizontal concentric-cylinder, or Couette, device has been studied in order to
      assess its role in the axial concentration banding observed in this flow. The
      flow is driven by rotation of the inner cylinder. The banding phenomenon is
      characterized by particle-rich bands which under flow appear as elevated regions
      at the free surface separated axially by regions dilute relative to the mean
      concentration. The concentric cylinders studied had outer radius R(o) = 2.22 cm
      and inner radii R(i) = 0.64, 0.95 and 1.27 cm; the suspension, of bulk particle
      volume fraction phi = 0.2 in all experiments described, was composed of particles
      of either 250-300 microm diameter or less than 106 microm diameter, with the
      suspending fluid an equal density liquid of viscosity 160 P. The ratio of the
      maximum to the minimum particle volume fraction along the axis in the segregated
      condition varies from O(1) to infinite. The latter case implies complete
      segregation, with bands of clear fluid separating the concentrated bands. The
      film depth has been varied through variation of the filled fraction, f, of the
      annular gap between the cylinders and through the rotation rate. Film depth was
      analysed by edge detection of video images of the free surface under flow, and
      the time required for band formation was determined for all conditions at which
      film depth was studied. The film depth increases roughly as the square root of
      rotation speed for f = 0.5. Band formation is more rapid for thicker films
      associated with more rapid rotation rates at f = 0.5, whereas slower formation
      rates are observed with thicker films caused by large f, f > 0.65. It is observed
      that the film depth over the inner cylinder grows prior to onset of banding, for
      as yet unknown reasons. A mechanism for segregation of particles and liquid in
      film flows based upon 'differential drainage' of the particle and liquid phase in
      the gravity-driven flow within the film over the inner cylinder is formulated to
      describe the onset of concentration fluctuations. This model predicts that
      suspension drainage flows lead to growth of fluctuations in phi under regions of
      negative surface curvature.

PMID- 12804221
TI  - Influence of particles on the transition to turbulence in pipe flow.
AB  - We investigate by experiment the influence of suspended solids upon the
      transition to turbulence in pipe flow. The particles are monodisperse and
      neutrally buoyant with the liquid. The role of the particles on the transition
      depends upon both the volume fraction, phi, and particle size. Below a critical
      particle diameter, particles alter the transition to larger critical Reynolds
      numbers for all phi. In contrast to this, larger particles move the transition to
      smaller Reynolds numbers for small phi, but they delay the transition at larger
      concentration.

PMID- 12804222
TI  - Assessment of the local stress state through macroscopic variables.
AB  - Macroscopic quantities beyond effective elastic tensors are presented that can be
      used to assess the local state of stress within a composite in the linear elastic
      regime. These are presented in a general homogenization context. It is shown that
      the gradient of the effective elastic property can be used to develop a lower
      bound on the maximum pointwise equivalent stress in the fine-scale limit. Upper
      bounds are more sensitive and are correlated with the distribution of states of
      the equivalent stress in the finescale limit. The upper bounds are given in terms
      of the macrostress modulation function. This function gauges the magnitude of the
      actual stress. For 1 </= p < infinity, upper bounds are found on the limit
      superior of the sequence of L(p) norms of stresses associated with discrete
      microstructure in the fine-scale limit. Conditions are given for which upper
      bounds can be found on the limit superior of the sequence of L(infinity) norms of
      stresses associated with the discrete microstructure in the fine-scale limit. For
      microstructure with oscillation on a sufficiently small scale we are able to give
      pointwise bounds on the actual stress in terms of the macrostress modulation
      function.

PMID- 12804223
TI  - On the homogenized behaviour of reinforced and other Bingham composites.
AB  - A recently developed (Ponte Castaneda 2002 J. Mech. Phys. Solids 50, 737-757)
      'second-order' nonlinear homogenization method is used to estimate the
      constitutive response of reinforced and other Bingham composites. For the special
      case of rigidly reinforced Bingham composites with overall isotropy (in two
      dimensions), the results show that the homogenized response of such materials is
      not strictly Bingham. Thus, instead of a purely linear incremental response
      beyond the relevant threshold (yield) stress, the response is strongly nonlinear
      just after yield and asymptotes to a purely linear incremental response only at
      sufficiently large stress or strain-rate levels. This phenomenon is linked to the
      presence of strong fluctuations of the strain-rate field in the composite at the
      onset of yield.

PMID- 12804224
TI  - Random formation, inelastic response and scale effects in paper.
AB  - We consider the constitutive law of paper and its relation to a spatially
      inhomogeneous, random paper structure, the so-called formation. Under biaxial
      tensile loading, paper may be taken as an elastic-plastic hardening material,
      modelled here by a hyperbolic tangent law. The fact that paper is a quasi-two
      dimensional solid offers a chance to inspect its formation via a basis-weight
      distribution (mass per unit area), and then carry out cross-correlations of two
      planar fields: the formation versus the strain (or stress) field resulting from a
      fine-mesh finite-element simulation of a sheet of paper subjected to a specified
      in-plane loading. The simulation requires an assumption of constitutive
      coefficients as a function of formation, and the higher the resultant cross
      correlation, the better the assumed constitutive law. With this methodology we
      conclude that the higher the basis-weight, the higher the local stiffness and
      strength of the paper (on millimetre scales) in two very different cases: a
      Crayola sketch-paper and a paperboard. We next set up a Boolean model of paper
      formation, where each grain plays the role of a floc of cellulose fibres. First,
      we employ a computational-mechanics fibre-network model to demonstrate the
      effects of formation on non-uniform strain fields in the elastic regime. Moving
      on to the inelastic regime, we treat flocs as continuum ellipses, and, employing
      the resulting relation between formation and constitutive coefficients, we study
      scale-dependent homogenization of paper and establish that the representative
      volume element in the sense of Hill (1963 J. Mech. Phys. Solids 11, 357-372) is
      approximately reached on scales about 10 times larger than the floc size.

PMID- 12804225
TI  - Explicit relations between elastic and conductive properties of materials
      containing annular cracks.
AB  - The impact of annular cracks on the effective elastic and conductive properties
      of a material is analysed. The compliance contribution tensor of an annular crack
      - the quantity that determines the increase in compliance of a solid due to
      introduction of such a crack - is derived analytically. The resistivity
      contribution tensor of an annular crack is calculated numerically. It is shown
      that an effective circular crack, i.e. a crack which yields the same change in
      elastic/conductive properties of a material as the given annular crack, can be
      chosen to match both of these tensors. Using this result, the explicit relation
      between elastic and conductive properties of a material containing annular cracks
      is obtained. The relation is derived using a non-interaction approximation.
      Applicability of the derived formulae to real materials (to plasma-sprayed
      coatings, in particular) is discussed.

PMID- 12804226
TI  - Systematic design of phononic band-gap materials and structures by topology
      optimization.
AB  - Phononic band-gap materials prevent elastic waves in certain frequency ranges
      from propagating, and they may therefore be used to generate frequency filters,
      as beam splitters, as sound or vibration protection devices, or as waveguides. In
      this work we show how topology optimization can be used to design and optimize
      periodic materials and structures exhibiting phononic band gaps. Firstly, we
      optimize infinitely periodic band-gap materials by maximizing the relative size
      of the band gaps. Then, finite structures subjected to periodic loading are
      optimized in order to either minimize the structural response along boundaries
      (wave damping) or maximize the response at certain boundary locations
      (waveguiding).

PMID- 12804227
TI  - Genetic design of solids possessing a random-particulate microstructure.
AB  - There exists a variety of difficulties in the computational design of macroscopic
      solid material properties formed by doping a homogeneous base matrix material
      with randomly distributed particles having different properties. Three primary
      problems are (1) the wide array of free microdesign variables, such as particle
      topology, property phase contrasts and volume fraction, which render the
      associated objective functions to be highly non-convex; (2) that the associated
      objective functions are not differentiable with respect to design variables,
      primarily due to prescribed constraints, such as prespecified restrictions on the
      microscale stress-field behaviour; and (3) the effective responses of various
      finite-sized samples, of equal volume but of different random particle
      distributions, exhibit mutual fluctuations, leading to amplified noise in
      optimization strategies where objective function sensitivities or comparisons are
      needed. The focus of this paper is the development of a statistical genetic
      algorithm which can handle difficulties due to non-convexity, lack of regularity
      and size effects. Theoretical properties of the overall approach are
      investigated. Semi-analytical and large-scale numerical examples, involving
      finite-element type discretizations, are given to illustrate its practical
      application.

PMID- 12804229
TI  - A variational formulation of three-dimensional steady water waves.
AB  - We are concerned with a three-dimensional layer of a perfect and irrotational
      liquid of density one (e.g. water) in a gravity field pointing vertically
      downwards. The layer is of infinite depth and bounded above by a free surface.
      Babenko developed a variational theory of steady periodic two-dimensional water
      waves without surface tension, and the aim of this paper is to extend Babenko's
      formulation to three-dimensional steady periodic waves.

PMID- 12804230
TI  - Non-existence of solitary water waves in three dimensions.
AB  - In the subject of free-surface water waves, solitary waves play an important role
      in the theory of two-dimensional fluid motions. These are steady solutions to the
      Euler equations that are localized, positively elevated above the mean fluid
      level and travelling at velocities with supercritical Froude number. They provide
      a stable mechanism in bodies of water for transport of mass, momentum and energy
      over long distances. In this paper, we prove that in the three- (or higher-)
      dimensional problem of surface water waves, there do not exist any localized
      steady positive solutions to the Euler equations.

PMID- 12804231
TI  - Steady two-layer flows over an obstacle.
AB  - Nonlinear waves in a forced channel flow of two contiguous homogeneous fluids of
      different densities are considered. Each fluid layer is of finite depth. The
      forcing is due to an obstruction lying on the bottom. The study is restricted to
      steady flows. First a weakly nonlinear analysis is performed. At leading order
      the problem reduces to a forced Korteweg-de Vries equation, except near a
      critical value of the ratio of layer depths which leads to the vanishing of the
      nonlinear term. The weakly nonlinear results obtained by integrating the forced
      Korteweg-de Vries equation are validated by comparison with numerical results
      obtained by solving the full governing equations. The numerical method is based
      on boundary integral equation techniques. Although the problem of two-layer flows
      over an obstacle is a classical problem, several branches of solutions which have
      never been computed before are obtained.

PMID- 12804232
TI  - Long-time asymptotics of the Navier-Stokes and vorticity equations on R(3).
AB  - We use the vorticity formulation to study the long-time behaviour of solutions to
      the Navier-Stokes equation on R(3). We assume that the initial vorticity is small
      and decays algebraically at infinity. After introducing self-similar variables,
      we compute the long-time asymptotics of the rescaled vorticity equation up to
      second order. Each term in the asymptotics is a self-similar divergence-free
      vector field with Gaussian decay at infinity, and the coefficients in the
      expansion can be determined by solving a finite system of ordinary differential
      equations. As a consequence of our results, we are able to characterize the set
      of solutions for which the velocity field satisfies ||u(.,t)||(L(2)) = o(t(-5/4))
      as t-->+ infinity. In particular, we show that these solutions lie on a smooth
      invariant submanifold of codimension 11 in our function space.

PMID- 12804233
TI  - A dimension-breaking phenomenon in the theory of steady gravity-capillary water
      waves.
AB  - The existence of a line solitary-wave solution to the water-wave problem with
      strong surface-tension effects was predicted on the basis of a model equation in
      the celebrated 1895 paper by D. J. Korteweg and G. de Vries and rigorously
      confirmed a century later by C. J. Amick and K. Kirchgassner in 1989. A model
      equation derived by B. B. Kadomtsev and V. I. Petviashvili in 1970 suggests that
      the Korteweg-de Vries line solitary wave belongs to a family of periodically
      modulated solitary waves which have a solitary-wave profile in the direction of
      motion and are periodic in the transverse direction. This prediction is
      rigorously confirmed for the full water-wave problem in the present paper. It is
      shown that the Korteweg-de Vries solitary wave undergoes a dimension-breaking
      bifurcation that generates a family of periodically modulated solitary waves. The
      term dimension-breaking phenomenon describes the spontaneous emergence of a
      spatially inhomogeneous solution of a partial differential equation from a
      solution which is homogeneous in one or more spatial dimensions.

PMID- 12804234
TI  - Gravity travelling waves for two superposed fluid layers, one being of infinite
      depth: a new type of bifurcation.
AB  - In this paper, we study the travelling gravity waves in a system of two layers of
      perfect fluids, the bottom one being infinitely deep, the upper one having a
      finite thickness h. We assume that the flow is potential and the dimensionless
      parameters are the ratio between densities rho = rho(2)/rho(1) and lambda =
      gh/c(2). We study special values of the parameters such that lambda(1 - rho) is
      near 1(-), where a bifurcation of a new type occurs. We formulate the problem as
      a spatial reversible dynamical system, where U = 0 corresponds to a uniform state
      (velocity c in a moving reference frame), and we consider the linearized operator
      around 0. We show that its spectrum contains the entire real axis (essential
      spectrum), with, in addition, a double eigenvalue in 0, a pair of simple
      imaginary eigenvalues +/-ilambda at a distance O(1) from 0, and for lambda(1 -
      rho) above 1, another pair of simple imaginary eigenvalues tending towards 0 as
      lambda(1 - rho) --> 1(+). When lambda(1 - rho) <or= 1, this pair disappears into
      the essential spectrum. The rest of the spectrum lies at a distance at least O(1)
      from the imaginary axis. We show in this paper that for lambda(1 - rho) close to
      1(-) there is a family of periodic solutions similar to that in the Lyapunov
      Devaney theorem (despite the resonance due to the point 0 in the spectrum).
      Moreover, showing that the full system can be seen as a perturbation of the
      Benjamin-Ono equation, coupled with a nonlinear oscillation, we also prove the
      existence of a family of homoclinic connections to these periodic orbits,
      provided that these ones are not too small.

PMID- 12804235
TI  - On the energetic stability of solitary water waves.
AB  - We study solutions of the water-wave problem for a fluid layer of finite depth in
      the presence of gravity and surface tension. We use the canonical Hamiltonian
      formulation by Zakharov in terms of the surface elevation and the trace of the
      velocity potential on the surface. With a new continuity result for the Dirichlet
      Neumann operator in terms of the surface as a function in H(1)(R), we show
      conditional energetic stability of the trivial solution in certain regions of the
      parameter space. In the same region we obtain stability of solitary waves under
      the additional assumption that the second variation of the energy has only one
      negative eigenvalue. The latter assumption is shown to be fulfilled for the small
      amplitude solitary waves first constructed by Amick & Kirchgassner.

PMID- 12804236
TI  - Forty years on from Aerobee 150: a personal perspective.
AB  - X-ray astronomy has evolved from a chance beginning 40 years ago to become a
      major branch of observational astronomy, underpinning a revolution in high-energy
      astrophysics. The intervening development can be seen in three phases, starting
      in the 1960s with a decade of pioneering exploration with sounding rockets, and
      consolidated by further discoveries with a series of dedicated small satellites,
      led by Uhuru, building up to NASA's HEAO-1 and Einstein Observatory missions in
      1978-1981. The remaining years of the last century saw X-ray astronomy become a
      broad international effort with strong contributions from Europe and Japan
      balancing a temporary loss of momentum in the NASA programme. A brief account of
      those early years in X-ray astronomy is given, from a personal (UK) perspective,
      as an introduction to the review of the current status of the discipline, which
      was the subject of the Discussion Meeting.

PMID- 12804237
TI  - X-ray spectroscopy of astrophysical plasmas.
AB  - We provide a qualitative review of key X-ray spectral diagnostics of
      astrophysical plasmas. We begin with a brief discussion of the two major types of
      equilibria, collisional ionization and photoionization, and then consider the
      behaviour of hydrogen-like, helium-like, iron L-shell and iron K-shell
      transitions for these separate cases. Where possible, we discuss explicit
      examples using high-resolution spectra acquired by the grating instruments on the
      Chandra and XMM-Newton observatories.

PMID- 12804238
TI  - X-rays from stars.
AB  - More than two years of observation with Chandra and XMM-Newton has provided a
      rich harvest of new results on the physics of stellar coronae and winds. High
      resolution X-ray spectroscopy in particular has opened new windows to the
      structure, the dynamics and the composition of stellar atmospheres. The present
      paper presents selected results from the areas of hot and cool stars and star
      formation, summarizing new views of the thermal structure and energy release in
      stellar coronae, observations of magnetically active brown dwarfs, the structure
      of winds in hot stars, the physics in colliding-wind binary systems, and X-rays
      from protostars and stellar jets.

PMID- 12804239
TI  - X-ray observations of accreting white-dwarf systems.
AB  - Accretion in white-dwarf binary systems can occur through discs, accretion
      columns or a combination of these, depending on the magnetic field of the white
      dwarf. Recent high-quality X-ray observations with the XMM-Newton and Chandra
      observatories have significantly advanced our understanding of the physics of the
      accretion process, and place severe tests on our existing models. There have been
      some surprises, such as the strong dependence of atmospheric heating on accretion
      rate. However, we believe that we are now confident that we understand in general
      the physical processes in the accretion region, although some complicating
      factors, such as absorption, remain. We also discuss new developments in ultra
      short-period white-dwarf binary systems.

PMID- 12804240
TI  - Accretion flows in X-ray binaries.
AB  - I review the X-ray observations of galactic accreting black holes and neutron
      stars and interpretations of these in terms of solutions of the accretion flow
      equations.

PMID- 12804241
TI  - Recent X-ray observations of supernova remnants.
AB  - The imaging and spectral capabilities of the Chandra X-ray Observatory and XMM
      Newton are extremely well suited for studying the remnants of supernovae. High
      resolution imaging over the band 0.1-10 keV maps the detailed structure of the
      supernova remnant, delineates the forward and reverse shock fronts and
      facilitates proper motion studies of the expanding material. High-resolution
      spectroscopy enables detailed diagnostics of the emitting plasma, including
      temperatures, ionization balance and abundances. Spectroscopy also reveals
      Doppler velocities along the line of sight. Most powerful is the capability for
      imaging spectroscopy, which can probe the progressive ionization at the shock
      fronts, the elemental distribution in the ejecta, and Doppler imaging. Examples
      are drawn from recent studies of oxygen-rich supernova remnants of various ages.

PMID- 12804242
TI  - Luminous X-ray sources in spiral and star-forming galaxies.
AB  - For studies of discrete X-ray source populations in nearby galaxies, high spatial
      resolution is a key to making progress. Now, for the first time, using the
      Chandra X-ray observatory, we are able to study these source populations in
      detail for galaxies beyond M31 and our local group galaxies. Analysis of
      accretion-driven and supernova-related discrete sources provides a new
      perspective on the evolution of galactic stellar populations, as well as giving
      insights into the physical mechanisms operating in individual cases. A
      particularly intriguing area, which we are only just beginning to address, is the
      nature of the most X-ray-luminous sources that are being discovered in many
      spiral and star-forming galaxies.

PMID- 12804243
TI  - Cosmological constraints from Chandra observations of galaxy clusters.
AB  - Chandra observations of rich, relaxed galaxy clusters allow the properties of the
      X-ray gas and the total gravitating mass to be determined precisely. Here, we
      present results for a sample of the most X-ray luminous, dynamically relaxed
      clusters known. We show that the Chandra data and independent gravitational
      lensing studies provide consistent answers on the mass distributions in the
      clusters. The mass profiles exhibit a form in good agreement with the predictions
      from numerical simulations. Combining Chandra results on the X-ray gas mass
      fractions in the clusters with independent measurements of the Hubble constant
      and the mean baryonic matter density in the Universe, we obtain a tight
      constraint on the mean total matter density of the Universe, Omega(m), and an
      interesting constraint on the cosmological constant, Omega(Lambda). We also
      describe the 'virial relations' linking the masses, X-ray temperatures and
      luminosities of galaxy clusters. These relations provide a key step in linking
      the observed number density and spatial distribution of clusters to the
      predictions from cosmological models. The Chandra data confirm the presence of a
      systematic offset of ca. 40% between the normalization of the observed mass
      temperature relation and the predictions from standard simulations. This finding
      leads to a significant revision of the best-fit value of sigma(8) inferred from
      the observed temperature and luminosity functions of clusters.

PMID- 12804244
TI  - Clusters of galaxies: a cosmological probe.
AB  - The constraints on cosmological parameters presently obtained and those that can
      be obtained from X-ray cluster surveys are presented. Extremely strong bounds on
      the values of Omega, Lambda, sigma(8) and the power spectrum of fluctuations, as
      well as constraints on the equation of state of dark energy, can be determined.
      Recent Advanced Satellite for Cosmology and Astrophysics and XMM results on the
      chemical composition of clusters show that the Fe abundance is not universal, but
      is correlated with cluster mass and central gas density. The Si, S and Fe
      abundances do not resemble those seen in Milky Way Halo stars or those in the
      Lyman-limit galaxies. The XMM RGS abundances for gas in elliptical galaxies are
      subsolar and the abundance pattern is not alpha-element rich, in contradiction
      with all models of elliptical-galaxy gas abundances.

PMID- 12804245
TI  - X-rays from active galactic nuclei: relativistically broadened emission lines.
AB  - The X-ray spectra of many Seyfert 1 galaxies show an iron-K emission line. Some
      of these lines are broad and skew, reflecting the rapid motion of the accreting
      gas together with the deep gravitational potential of the central black hole. The
      observational evidence for broad iron lines is reviewed, from ASCA to recent
      Chandra and XMM-Newton spectra. Examples are shown from MCG-6-30-15, for which
      line variability is discussed. Current results indicate that we are studying
      accretion flows well within 6GM/c(2).

PMID- 12804246
TI  - Obscured active galactic nuclei: the hidden side of the X-ray Universe.
AB  - Most active galactic nuclei (AGN) are 'obscured', i.e. the nucleus is hiding
      behind a screen of absorbing material. The advantage of having the nucleus
      obscured is to make easier the observations of those emission components which
      originate in circumnuclear matter outside the absorbing regions, because in this
      case they are not outshone by the nuclear emission. This is particularly
      important in X-rays, where spatial resolution is (with the notable exception of
      Chandra) poorer than in the optical, and the study of circumnuclear regions is
      often based on spectral analysis only. The properties of circumnuclear matter, in
      the light of recent high spectral and/or angular resolution Chandra and XMM
      Newton observations, are reviewed and discussed in the framework of the
      unification model. Recent discoveries of X-ray obscured Seyfert 1, and of X-ray
      loud but optically normal galaxies, are calling for a revision of the unification
      model. Obscured AGN have also a cosmological relevance. Not only are they a
      fundamental ingredient of synthesis models of the cosmic X-ray background (XRB),
      but provide a link between the XRB and the cosmic infrared background.

PMID- 12804247
TI  - The Chandra Deep Field-North Survey and the cosmic X-ray background.
AB  - Chandra has performed a 1.4 Ms survey centred on the Hubble Deep Field-North (HDF
      N), probing the X-ray Universe 55-550 times deeper than was possible with pre
      Chandra missions. We describe the detected point and extended X-ray sources and
      discuss their overall multi-wavelength (optical, infrared, submillimetre and
      radio) properties. Special attention is paid to the HDF-N X-ray sources, luminous
      infrared starburst galaxies, optically faint X-ray sources and high-to-extreme
      redshift active galactic nuclei. We also describe how stacking analyses have been
      used to probe the average X-ray-emission properties of normal and starburst
      galaxies at cosmologically interesting distances. Finally, we discuss plans to
      extend the survey and argue that a 5-10 Ms Chandra survey would lay key
      groundwork for future missions such as XEUS and Generation-X.

PMID- 12804248
TI  - Hunting the first black holes.
AB  - Deep X-ray surveys have shown that the cosmic X-ray background (XRB) is largely
      due to the accretion onto supermassive black holes, integrated over the cosmic
      time. The Rontgensatellit (ROSAT), Chandra and XMM-Newton satellites have
      resolved more than 80% of the 0.1-10 keV X-ray background into discrete sources.
      Optical spectroscopic identifications are ca. 90% and 60% complete, for the
      deepest ROSAT and Chandra/XMM-Newton surveys, respectively, and show that the
      sources producing the bulk of the X-ray background are a mixture of obscured
      (type-1) and unobscured (type-2) active galactic nuclei (AGN), as predicted by
      the XRB population-synthesis models, following the unified AGN scenarios. The
      characteristic hard spectrum of the XRB can be explained if most of the AGN are
      heavily absorbed and, in particular, a class of highly luminous type-2 AGN, so
      called QSO-2s, exist. The Chandra and XMM-Newton satellites have recently
      detected several examples of QSO-2s. The space density of the X-ray selected AGN,
      as determined from ROSAT surveys, does not seem to decline as rapidly as that of
      optically selected QSOs; however, the statistics of the high-redshift samples is
      still rather poor. The new Chandra and XMM-Newton surveys at significantly
      fainter fluxes are starting to provide additional constraints here, but the
      preliminary observed redshift distribution peaks at much lower redshifts (z = 0.5
      1) than the predictions based on the ROSAT data. Nevertheless, there is an
      indication of a decline of the space density of X-ray-selected AGN at redshifts
      above four.

PMID- 12804249
TI  - X-ray astronomy in the new millennium: a summary.
AB  - Recent X-ray observations have had a major impact on topics ranging from proto
      stars to cosmology. They have also drawn attention to important and general
      physical processes that currently limit our understanding of thermal and non
      thermal X-ray sources. These include unmeasured atomic astrophysics data
      (wavelengths, oscillator strengths, etc.), basic hydromagnetic processes (e.g.
      shock structure, reconnection), plasma processes (such as electron-ion
      equipartition and heat conduction) and radiative transfer (in discs and accretion
      columns). Progress on these problems will probably come from integrative studies
      that draw upon observations, throughout the electromagnetic spectrum, of
      different classes of source. X-ray observations are also giving a new perspective
      on astronomical subjects, like the nature of galactic nuclei and the evolution of
      stellar populations. In addition, they are helping us to address central
      cosmological questions, including the measurement of the matter content of the
      Universe, understanding its overall luminosity density, describing its chemical
      evolution and locating the first luminous objects. X-ray astronomy has a healthy
      future with several international space missions under construction and in
      development.

PMID- 12804251
TI  - Predictions of extreme precipitation and sea-level rise under climate change.
AB  - Two aspects of global climate change are particularly relevant to river and
      coastal flooding: changes in extreme precipitation and changes in sea level. In
      this paper we summarize the relevant findings of the IPCC Third Assessment Report
      and illustrate some of the common results found by the current generation of
      coupled atmosphere-ocean general circulation models (AOGCMs), using the Hadley
      Centre models. Projections of changes in extreme precipitation, sea-level rise
      and storm surges affecting the UK will be shown from the Hadley Centre regional
      models and the Proudman Oceanographic Laboratory storm-surge model. A common
      finding from AOGCMs is that in a warmer climate the intensity of precipitation
      will increase due to a more intense hydrological cycle. This leads to reduced
      return periods (i.e. more frequent occurrences) of extreme precipitation in many
      locations. The Hadley Centre regional model simulates reduced return periods of
      extreme precipitation in a number of flood-sensitive areas of the UK. In
      addition, simulated changes in storminess and a rise in average sea level around
      the UK lead to reduced return periods of extreme high coastal water events. The
      confidence in all these results is limited by poor spatial resolution in global
      coupled models and by uncertainties in the physical processes in both global and
      regional models, and is specific to the climate change scenario used.

PMID- 12804252
TI  - Evidence for trends in UK flooding.
AB  - Recent major flooding in the UK has raised concern that climate change is causing
      increases in flood frequency and flood magnitude. This paper considers whether UK
      flood data provide evidence of increasing trends in fluvial floods. The analysis
      examines both local and national flood series and investigates the effect of
      climate variability on trend detection. The results suggest that there have been
      trends towards more protracted high flows over the last 30-50 years, but that
      this could be accounted for as part of climatic variation rather than climate
      change. There is no statistical evidence of a long-term trend in flooding over
      the last 80-120 years. Thus, although climate change could be influencing floods,
      direct analysis of flood records does not yet provide proof.

PMID- 12804253
TI  - Developments in radar and remote-sensing methods for measuring and forecasting
      rainfall.
AB  - Over the last 25 years or so, weather-radar networks have become an integral part
      of operational meteorological observing systems. While measurements of rainfall
      made using radar systems have been used qualitatively by weather forecasters, and
      by some operational hydrologists, acceptance has been limited as a consequence of
      uncertainties in the quality of the data. Nevertheless, new algorithms for
      improving the accuracy of radar measurements of rainfall have been developed,
      including the potential to calibrate radars using the measurements of attenuation
      on microwave telecommunications links. Likewise, ways of assimilating these data
      into both meteorological and hydrological models are being developed. In this
      paper we review the current accuracy of radar estimates of rainfall, pointing out
      those approaches to the improvement of accuracy which are likely to be most
      successful operationally. Comment is made on the usefulness of satellite data for
      estimating rainfall in a flood-forecasting context. Finally, problems in coping
      with the error characteristics of all these data using both simple schemes and
      more complex four-dimensional variational analysis are being addressed, and are
      discussed briefly in this paper.

PMID- 12804254
TI  - The challenge of predicting flash floods from thunderstorm rainfall.
AB  - A major characteristic of the hydrometeorology of semi-arid regions is the
      occurrence of intense thunderstorms that develop very rapidly and cause severe
      flooding. In summer, monsoon air mass is often of subtropical origin and is
      characterized by convective instability. The existing observational network has
      major deficiencies for those regions in providing information that is important
      to run-off generation. Further, because of the complex interactions between the
      land surface and the atmosphere, mesoscale atmospheric models are currently able
      to reproduce only general features of the initiation and development of
      convective systems. In our research, several interrelated components including
      the use of satellite data to monitor precipitation, data assimilation of a
      mesoscale regional atmospheric model, modification of the land component of the
      mesoscale model to better represent the semi-arid region surface processes that
      control run-off generation, and the use of ensemble forecasting techniques to
      improve forecasts of precipitation and run-off potential are investigated. This
      presentation discusses our ongoing research in this area; preliminary results
      including an investigation related to the unprecedented flash floods that
      occurred across the Las Vegas valley (Nevada, USA) in July of 1999 are discussed.

PMID- 12804255
TI  - Reinforcing flood-risk estimation.
AB  - Flood-frequency estimation is inherently uncertain. The practitioner applies a
      combination of gauged data, scientific method and hydrological judgement to
      derive a flood-frequency curve for a particular site. The resulting estimate can
      be thought fully satisfactory only if it is broadly consistent with all that is
      reliably known about the flood-frequency behaviour of the river. The paper takes
      as its main theme the search for information to strengthen a flood-risk estimate
      made from peak flows alone. Extra information comes in many forms, including
      documentary and monumental records of historical floods, and palaeological
      markers. Meteorological information is also useful, although rainfall rarity is
      difficult to assess objectively and can be a notoriously unreliable indicator of
      flood rarity. On highly permeable catchments, groundwater levels present
      additional data. Other types of information are relevant to judging hydrological
      similarity when the flood-frequency estimate derives from data pooled across
      several catchments. After highlighting information sources, the paper explores a
      second theme: that of consistency in flood-risk estimates. Following publication
      of the Flood estimation handbook, studies of flood risk are now using digital
      catchment data. Automated calculation methods allow estimates by standard methods
      to be mapped basin-wide, revealing anomalies at special sites such as river
      confluences. Such mapping presents collateral information of a new character. Can
      this be used to achieve flood-risk estimates that are coherent throughout a river
      basin?

PMID- 12804256
TI  - Floods: some probabilistic and statistical approaches.
AB  - Some of the many statistical aspects of floods are discussed and some new results
      are given on a number of features. The probability theory of extreme values is
      briefly reviewed and its potential for applications outlined. The peaks-over
      threshold method of estimation is compared with the direct use of annual maxima
      and some theoretical comparisons of efficiency are given. The effect of trend on
      the distribution of maxima is analysed in terms of a simple theoretical model
      distinguishing the effects of trend in mean level and of trend in dispersion. An
      empirical Bayes method for pooling information from a number of sources is
      described and illustrated, and related to the procedures recommended in the Flood
      estimation handbook. In the final section, a range of further issues is outlined.

PMID- 12804257
TI  - Progress in and prospects for fluvial flood modelling.
AB  - Recent floods in the UK have raised public and political awareness of flood risk.
      There is an increasing recognition that flood management and land-use planning
      are linked, and that decision-support modelling tools are required to address
      issues of climate and land-use change for integrated catchment management. In
      this paper, the scientific context for fluvial flood modelling is discussed,
      current modelling capability is considered and research challenges are
      identified. Priorities include (i) appropriate representation of spatial
      precipitation, including scenarios of climate change; (ii) development of a
      national capability for continuous hydrological simulation of ungauged
      catchments; (iii) improved scientific understanding of impacts of agricultural
      land-use and land-management change, and the development of new modelling
      approaches to represent those impacts; (iv) improved representation of urban
      flooding, at both local and catchment scale; (v) appropriate parametrizations for
      hydraulic simulation of in-channel and flood-plain flows, assimilating available
      ground observations and remotely sensed data; and (vi) a flexible decision
      support modelling framework, incorporating developments in computing, data
      availability, data assimilation and uncertainty analysis.

PMID- 12804258
TI  - Advances in real-time flood forecasting.
AB  - This paper discusses the modelling of rainfall-flow (rainfall-run-off) and flow
      routeing processes in river systems within the context of real-time flood
      forecasting. It is argued that deterministic, reductionist (or 'bottom-up')
      models are inappropriate for real-time forecasting because of the inherent
      uncertainty that characterizes river-catchment dynamics and the problems of model
      over-parametrization. The advantages of alternative, efficiently parametrized
      data-based mechanistic models, identified and estimated using statistical
      methods, are discussed. It is shown that such models are in an ideal form for
      incorporation in a real-time, adaptive forecasting system based on recursive
      state-space estimation (an adaptive version of the stochastic Kalman filter
      algorithm). An illustrative example, based on the analysis of a limited set of
      hourly rainfall-flow data from the River Hodder in northwest England,
      demonstrates the utility of this methodology in difficult circumstances and
      illustrates the advantages of incorporating real-time state and parameter
      adaption.

PMID- 12804259
TI  - Advances in urban-drainage management and flood protection.
AB  - Since the beginning of modern urban drainage in the 19th century, the sole
      objective has been to get rid of sewage and storm water in the best possible way
      and design the systems according to accepted standards. In recent decades,
      advanced methods have been developed not only to refine the design but also
      especially to enable the assessment of hydraulic performance and pollutant
      emissions. Consequently, urban drainage has become part of an integrated approach
      concerning flood protection as well as ecological aspects for whole watersheds.
      Another major change concerns the management of urban systems: simple structural
      maintenance has been replaced by interactive operational management and control
      of the systems in order to make better use of the facilities. Rehabilitation has
      become a multi-objective task. This paper looks at today's basic principles of
      urban drainage and tomorrow's potential advances, and deals with their relevance
      to flood protection.

PMID- 12804260
TI  - Coastal modelling for flood defence.
AB  - This paper reviews practices and trends in hydrodynamic and statistical analyses
      and modelling in the Netherlands with regard to the risk of coastal flooding. We
      restrict ourselves to the physical phenomena of tides, storm surges and wind
      waves. We first give a brief outline of established policy in the Netherlands
      regarding accepted levels of risk of flooding, and current changes therein. This
      is followed by a summary of a statistical reanalysis of historical storm-surge
      data combined with numerical hydrodynamic modelling, aimed at improved estimates
      of probabilities of occurrence of extreme water levels along the Dutch coast.
      Recent developments concerning the physical and numerical modelling of inundation
      of low-lying areas are presented. State-of-the-art modelling of wind waves in
      coastal areas is also reviewed. Research issues in the area of coastal modelling
      for flood defence are indicated.

PMID- 12804261
TI  - Estuarine flooding and managed retreat.
AB  - The concentration of industrial, residential and agricultural activity on the
      lowlands surrounding our estuaries has led to an increasing problem of flood risk
      in these areas. However, flood hazards have been, in large part, the result of
      past human interference in the estuary system and as such may be reduced by more
      enlightened management. This paper examines the problems of flood risk and
      discusses some of the research that has been conducted into its alleviation. In
      particular, it concentrates attention on the programme of 'managed retreat' in
      the UK, which attempts to restore previously reclaimed areas in order to reduce
      flooding and other hazards of the estuarine system.

PMID- 12804262
TI  - Ecological response to and management of increased flooding caused by climate
      change.
AB  - River channels and their flood plains are among the most naturally dynamic
      ecosystems on earth, in large part due to periodic flooding. The components of a
      river's natural flood regime (magnitude, frequency, duration and timing of peak
      flows) interact to maintain great habitat heterogeneity and to promote high
      species diversity and ecosystem productivity. Flood regimes vary within and among
      rivers, depending on catchment size, geology and regional hydroclimatology.
      Geographic variation in contemporary flood regimes results in river-to-river
      variation in ecosystem structure, and therefore in potential river ecosystem
      response to increased future flooding. The greater the deviation in flood regime
      from contemporary or recent historical conditions, the greater the expected
      ecological alteration. Ecological response will also depend on how extensively
      humans have altered natural river dynamics through land-use practices. Examples
      of human-caused changes in flood regime (e.g. urbanization, agricultural
      practices) provide analogues to explore the ecological implications of region
      specific climate change. In many settings where humans have severely modified
      rivers (e.g. through leveeing), more frequent larger floods will work to re
      establish connections with severed flood-plain and riparian wetlands in human
      dominated river valleys. Developing and implementing non-structural flood
      management policies based on ecological principles can benefit river ecosystems,
      as well as human society.

PMID- 12804263
TI  - Vulnerability to flooding: health and social dimensions.
AB  - This paper presents research results on the impacts that floods can have on the
      people affected, thus complementing the existing data on the monetary losses
      liable to occur in flood events. Both datasets should be used when deciding on
      investment in flood defence measures. We report on research on the vulnerability
      of flood-affected communities to adverse health effects, and the development of
      an index of community vulnerability based on extensive focus-group research and
      secondary-source census data.

PMID- 12804264
TI  - How can we learn to live with rivers? The findings of the Institution of Civil
      Engineers Presidential Commission on flood-risk management.
AB  - In the wake of the floods of 1998 and 2000 the Government invited the Institution
      of Civil Engineers (ICE) to carry out a technical review of flood-risk management
      in England and Wales and to consider the most appropriate approaches to flood
      risk management for the 21st century. The findings of this Commission are
      published in the ICE report Learning to live with rivers. Further information on
      the Commission and its work is available at www.icenet.org.uk/presidential.htm.
      This paper provides an introduction to the need for such a review and the scope
      of the Commission's work. A summary of the findings of the Commission are
      presented along with key recommendations for improved flood-risk management in
      the future.

PMID- 12804265
TI  - Floods in a changing climate: a review.
AB  - This paper begins with an analysis of flooding as a natural disaster for which
      the solutions to the environmental, social and economic problems are essentially
      those of identifying and overcoming hazards and vulnerability, reducing risk and
      damaging consequences. Long-term solutions to flooding problems, especially in a
      changing climate, should be sought in the wider context of developing more
      sustainable social organization, economics and technology. Then, developments are
      described of how scientific understanding, supported by practical modelling, is
      leading to predictions of how human-induced changes to climatic and geological
      conditions are likely to influence flooding over at least the next 300 years,
      through their influences on evaporation, precipitation, run-off, wind storm and
      sea-level rise. Some of the outstanding scientific questions raised by these
      problems are highlighted, such as the statistical and deterministic prediction of
      extreme events, the understanding and modelling of mechanisms that operate on
      varying length- and time-scales, and the complex interactions between biological,
      ecological and physical problems. Some options for reducing the impact of
      flooding by new technology include both improved prediction and monitoring with
      computer models, and remote sensing, flexible and focused warning systems, and
      permanent and temporary flood-reduction systems.

PMID- 12804266
TI  - New science from high-performance computing: an introduction.

PMID- 12804267
TI  - Promise and challenge of high-performance computing, with examples from molecular
      modelling.
AB  - Computational modelling is one of the most significant developments in the
      practice of scientific inquiry in the 20th century. During the past decade,
      advances in computing technologies have increased the speed of computers by a
      factor of 100; an increase of a factor of 1000 can be expected in the next
      decade. These advances have, however, come at a price, namely, radical change(s)
      in computer architecture. Will computational scientists and engineers be able to
      harness the power offered by these high-performance computers to solve the most
      critical problems in science and engineering? In this paper, we discuss the
      challenges that must be addressed if we are to realize the benefits offered by
      high-performance computing. The task will not be easy; it will require revision
      or replacement of much of the software developed for vector supercomputers as
      well as advances in a number of key theoretical areas. Because of the pace of
      computing advances, these challenges must be met by close collaboration between
      computational scientists, computer scientists and applied mathematicians. The
      effectiveness of such a multidisciplinary approach is illustrated in a brief
      review of NWCHEM, a general-purpose computational chemistry code designed for
      parallel supercomputers.

PMID- 12804268
TI  - Computational physics: a perspective.
AB  - Computing comprises three distinct strands: hardware, software and the ways they
      are used in real or imagined worlds. Its use in research is more than writing or
      running code. Having something significant to compute and deploying judgement in
      what is attempted and achieved are especially challenging. In science or
      engineering, one must define a central problem in computable form, run such
      software as is appropriate and, last but by no means least, convince others that
      the results are both valid and useful. These several strands are highly
      interdependent. A major scientific development can transform disparate aspects of
      information and computer technologies. Computers affect the way we do science, as
      well as changing our personal worlds. Access to information is being transformed,
      with consequences beyond research or even science. Creativity in research is
      usually considered uniquely human, with inspiration a central factor. Scientific
      and technological needs are major forces in innovation, and these include
      hardware and software opportunities. One can try to define the scientific needs
      for established technologies (atomic energy, the early semiconductor industry),
      for rapidly developing technologies (advanced materials, microelectronics) and
      for emerging technologies (nanotechnology, novel information technologies). Did
      these needs define new computing, or was science diverted into applications of
      then-available codes? Regarding credibility, why is it that engineers accept
      computer realizations when designing engineered structures, whereas predictive
      modelling of materials has yet to achieve industrial confidence outside very
      special cases? The tensions between computing and traditional science are
      complex, unpredictable and potentially powerful.

PMID- 12804269
TI  - Simulation of the strong interaction.
AB  - In the Standard Model (SM) of particle physics, quarks are permanently confined
      by the strong interaction into bound states called hadrons. The values of some
      parameters, such as the quark masses and the strengths of the decays of one quark
      flavour into another, cannot be measured directly and must be deduced from
      experiments on hadrons. This requires calculations of the strong-interaction
      effects within the bound states, which are only possible using numerical
      simulations of quantum chromodynamics (QCD), the quantum field theory of the
      strong interaction. In conjunction with experimental data from B factories over
      the next few years, QCD simulations may provide clues to physics beyond the SM.
      The simulations are computationally intensive and, for the past 20 years, have
      exploited leading-edge computing technology. This continues today, with a project
      to develop a 10 Tflops computer for QCD costing less than 1 US dollar per Mflops.

PMID- 12804270
TI  - Computational challenges in atomic, molecular and optical physics.
AB  - Six challenges are discussed. These are the laser-driven helium atom; the laser
      driven hydrogen molecule and hydrogen molecular ion; electron scattering (with
      ionization) from one-electron atoms; the vibrational and rotational structure of
      molecules such as H(3)(+) and water at their dissociation limits; laser-heated
      clusters; and quantum degeneracy and Bose-Einstein condensation. The first four
      concern fundamental few-body systems where use of high-performance computing
      (HPC) is currently making possible accurate modelling from first principles. This
      leads to reliable predictions and support for laboratory experiment as well as
      true understanding of the dynamics. Important aspects of these challenges
      addressable only via a terascale facility are set out. Such a facility makes the
      last two challenges in the above list meaningfully accessible for the first time,
      and the scientific interest together with the prospective role for HPC in these
      is emphasized.

PMID- 12804271
TI  - New challenges in quantum chemistry: Quests for accurate calculations for large
      molecular systems.
AB  - As quantum chemistry plays a more and more central role in many complicated
      chemical problems, it has become necessary to obtain accurate results for large
      molecular systems. Conventional quantum chemistry methods are either too
      expensive to apply to large systems or too approximate for the results to be
      reliable, and they fail to satisfy this requirement. A variety of different
      approaches is being developed with the aim of achieving this goal: local
      correlation methods; divide-and-conquer methods; linear-scaling density
      functional methods based on the fast multipole and other approximations;
      effective potential methods; and hybrid methods. ONIOM (our N-layered integrated
      molecular orbital plus molecular mechanics method), developed by the authors, is
      a hybrid method in which a large molecular system is divided into onion-skin-like
      layers, and different quantum chemistry/molecular mechanics methods are used for
      different parts of the system; the results are combined to extrapolatively
      estimate the results of high-level calculation for the real system. Several
      applications of ONIOM will be discussed.

PMID- 12804272
TI  - Simulations of biomolecules: Characterization of the early steps in the pH
      induced conformational conversion of the hamster, bovine and human forms of the
      prion protein.
AB  - As computer power increases, so too does the range of interesting biomolecular
      phenomena and properties that can be simulated. It is now possible to simulate
      complicated protein conformational changes at ambient or physiological
      temperatures. In this regard, we are attempting to map the conformational
      transitions of the normal, cellular prion protein (PrP(C)) to its infectious
      scrapie isoform (PrP(Sc)), which causes neurodegenerative diseases in many
      mammals. These two forms have identical sequences and are conformational isomers,
      with heightened formation of beta-sheet structure in the scrapie form. Conversion
      can be triggered by lowering the pH, but thus far it has been impossible to
      characterize the conformational change at high resolution using experimental
      methods. Therefore, to investigate the effect of acidic pH on PrP conformation,
      we have performed molecular-dynamics simulations of hamster, human and bovine
      forms of the prion protein in water at neutral and low pH. In all cases the core
      of the protein is well maintained at neutral pH. At low pH, however, the protein
      is more dynamic, and the sheet-like structure increases both by lengthening of
      the native beta-sheet and by addition of a portion of the N-terminus to widen the
      sheet by another 2-3 strands.

PMID- 12804273
TI  - Application of high-throughput computing in bioinformatics.
AB  - We describe the challenges faced when developing a Linux/PC-based cluster to
      apply bioinformatics algorithms to the rapidly increasing raw genomics data
      available. The calculations, which take around two months to complete, result in
      a powerful resource that can be used for data mining--most obviously for the
      human genome. Our current infrastructure consists of a 1314 node cluster with
      1734 processors supporting both production and research. This paper highlights
      the problems in achieving high data throughput with such systems and shows that
      raw computer power is only one component of a complex problem.

PMID- 12804274
TI  - Data Grids: a new computational infrastructure for data-intensive science.
AB  - Twenty-first-century scientific and engineering enterprises are increasingly
      characterized by their geographic dispersion and their reliance on large data
      archives. These characteristics bring with them unique challenges. First, the
      increasing size and complexity of modern data collections require significant
      investments in information technologies to store, retrieve and analyse them.
      Second, the increased distribution of people and resources in these projects has
      made resource sharing and collaboration across significant geographic and
      organizational boundaries critical to their success. In this paper I explore how
      computing infrastructures based on Data Grids offer data-intensive enterprises a
      comprehensive, scalable framework for collaboration and resource sharing. A
      detailed example of a Data Grid framework is presented for a Large Hadron
      Collider experiment, where a hierarchical set of laboratory and university
      resources comprising petaflops of processing power and a multi-petabyte data
      archive must be efficiently used by a global collaboration. The experience gained
      with these new information systems, providing transparent managed access to
      massive distributed data collections, will be applicable to large-scale, data
      intensive problems in a wide spectrum of scientific and engineering disciplines,
      and eventually in industry and commerce. Such systems will be needed in the
      coming decades as a central element of our information-based society.

PMID- 12804275
TI  - High-performance computing in computational fluid dynamics: progress and
      challenges.
AB  - Computational fluid dynamics (CFD) is by far the largest user of high-performance
      computing (HPC) in engineering. The main scientific challenge is the need to gain
      a greater understanding of turbulence and its consequences for the transfer of
      momentum, heat and mass in engineering applications, including aerodynamics,
      industrial flows and combustion systems. Availability of HPC has led to
      significant advances in direct numerical simulation (DNS) of turbulence and
      turbulent combustion, and has encouraged the development of large-eddy simulation
      (LES) for engineering flows. The statistical data generated by DNS have provided
      valuable insight into the physics of many turbulent flows and have led to rapid
      improvements in turbulence and combustion modelling for industry. Nevertheless,
      major challenges remain and the computational requirements for turbulence
      research, driven by well-established physical scaling laws, are likely to remain
      at the limit of the available HPC provision for some time to come.

PMID- 12804277
TI  - Computationally intensive econometrics using a distributed matrix-programming
      language.
AB  - This paper reviews the need for powerful computing facilities in econometrics,
      focusing on concrete problems which arise in financial economics and in
      macroeconomics. We argue that the profession is being held back by the lack of
      easy-to-use generic software which is able to exploit the availability of cheap
      clusters of distributed computers. Our response is to extend, in a number of
      directions, the well-known matrix-programming interpreted language Ox developed
      by the first author. We note three possible levels of extensions: (i) Ox with
      parallelization explicit in the Ox code; (ii) Ox with a parallelized run-time
      library; and (iii) Ox with a parallelized interpreter. This paper studies and
      implements the first case, emphasizing the need for deterministic computing in
      science. We give examples in the context of financial economics and time-series
      modelling.

PMID- 12804276
TI  - The ab initio simulation of the Earth's core.
AB  - The Earth has a liquid outer and solid inner core. It is predominantly composed
      of Fe, alloyed with small amounts of light elements, such as S, O and Si. The
      detailed chemical and thermal structure of the core is poorly constrained, and it
      is difficult to perform experiments to establish the properties of core-forming
      phases at the pressures (ca. 300 GPa) and temperatures (ca. 5000-6000 K) to be
      found in the core. Here we present some major advances that have been made in
      using quantum mechanical methods to simulate the high-P/T properties of Fe
      alloys, which have been made possible by recent developments in high-performance
      computing. Specifically, we outline how we have calculated the Gibbs free
      energies of the crystalline and liquid forms of Fe alloys, and so conclude that
      the inner core of the Earth is composed of hexagonal close packed Fe containing
      ca. 8.5% S (or Si) and 0.2% O in equilibrium at 5600 K at the boundary between
      the inner and outer cores with a liquid Fe containing ca. 10% S (or Si) and 8% O.

PMID- 12804278
TI  - The computational challenges of Earth-system science.
AB  - The Earth system--comprising atmosphere, ocean, land, cryosphere and biosphere-
      is an immensely complex system, involving processes and interactions on a wide
      range of space- and time-scales. To understand and predict the evolution of the
      Earth system is one of the greatest challenges of modern science, with success
      likely to bring enormous societal benefits. High-performance computing, along
      with the wealth of new observational data, is revolutionizing our ability to
      simulate the Earth system with computer models that link the different components
      of the system together. There are, however, considerable scientific and technical
      challenges to be overcome. This paper will consider four of them: complexity,
      spatial resolution, inherent uncertainty and time-scales. Meeting these
      challenges requires a significant increase in the power of high-performance
      computers. The benefits of being able to make reliable predictions about the
      evolution of the Earth system should, on their own, amply repay this investment.

PMID- 12804279
TI  - Simulating the formation of cosmic structure.
AB  - A timely combination of new theoretical ideas and observational discoveries has
      brought about significant advances in our understanding of cosmic evolution.
      Computer simulations have played a key role in these developments by providing
      the means to interpret astronomical data in the context of physical and
      cosmological theory. In the current paradigm, our Universe has a flat geometry,
      is undergoing accelerated expansion and is gravitationally dominated by
      elementary particles that make up cold dark matter. Within this framework, it is
      possible to simulate in a computer the emergence of galaxies and other structures
      from small quantum fluctuations imprinted during an epoch of inflationary
      expansion shortly after the Big Bang. The simulations must take into account the
      evolution of the dark matter as well as the gaseous processes involved in the
      formation of stars and other visible components. Although many unresolved
      questions remain, a coherent picture for the formation of cosmic structure is now
      beginning to emerge.

PMID- 12804280
TI  - The origins of the concept of interference.
AB  - The concept of interference is implicit in Newton's explanation of the anomaly of
      the tides in the Gulf of Tongkin, but Thomas Young was the first to generalize
      the principle and to apply it to compound tides, to auditory beats, and to the
      colours of thin films. In his Bakerian Lecture, delivered on 12 and 19 November
      1801, he was able to accurately derive the wavelengths of particular hues from
      Newton's measurements of the colours of thin plates. The first printed statement
      of the generalized principle of interference appears in the Syllabus for his
      Royal Institution lectures, which was published early in 1802. His celebrated two
      slit experiment is first described in his Course of Lectures on Natural
      Philosophy and the Mechanical Arts of 1807.

PMID- 12804281
TI  - Noise, anti-noise and fluid flow control.
AB  - This paper celebrates Thomas Young's discovery that wave interference was
      responsible for much that is known about light and colour. A substantial
      programme of work has been aimed at controlling the noise of aerodynamic flows.
      Much of that field can be explained in terms of interference and it is argued in
      this paper that the theoretical techniques for analysing noise can also be seen
      to rest on interference effects. Interference can change the character of wave
      fields to produce, out of well-ordered fields, wave systems quite different from
      the interfering wave elements. Lighthill's acoustic analogy is described as an
      example of this effect, an example in which the exact model of turbulence
      generated noise is seen to consist of elementary interfering sound waves; waves
      that are sometimes heard in advance of their sources. The paper goes on to
      describe an emerging field of technology where sound is suppressed by
      superimposing on it a destructively interfering secondary sound; one designed and
      manufactured specifically for interference. That sound is known as anti-sound, or
      anti-noise when the sound is chaotic enough. Examples are then referred to where
      the noisy effect to be controlled is actually a disturbance of a linearly
      unstable system; a disturbance that is destroyed by destructive interference with
      a deliberately constructed antidote. The practical benefits of this kind of
      instability control are much greater and can even change the whole character of
      flows. It is argued that completely unnatural unstable conditions can be held
      with active controllers generating destructively interfering elements. Examples
      are given in which gravitational instability of stratified fluids can be
      prevented. The Kelvin-Helmholtz instability of shear flows can also be avoided by
      simple controls. Those are speculative examples of what might be possible in
      future developments of an interference effect, which has made anti-noise a useful
      technology.

PMID- 12804282
TI  - Interference effects and phase sensitivity in hearing.
AB  - This paper reviews interference effects in the auditory system, particularly
      effects occurring in the outer ear and the inner ear (cochlea). Sounds enter the
      ear canal both directly and after reflections from the pinna. This results in
      complex spectral patterns, which vary systematically with the direction of
      incidence of the sound source relative to the head. Evidence is described
      indicating that these spectral patterns are used in the localization of sounds in
      space. The cochlea behaves like a limited-resolution frequency analyser. When the
      components of a complex sound are closely spaced in frequency, they can interfere
      on the basilar membrane (BM) within the cochlea. Interference effects on the BM
      are complex, as they are influenced by a physiologically active mechanism which
      introduces strong nonlinearities, including level-dependent amplification.
      Interference effects on the BM play a role in many aspects of auditory
      perception, including the perception of consonance and dissonance, the perception
      of pitch, the perception of changes in phase, and the perception of timbre.
      Interference effects in the cochlea may also play a role in producing the
      spectral regularity observed in sounds reflected from the ear (otoacoustic
      emissions).

PMID- 12804283
TI  - From structure to mechanism: electron crystallographic studies of
      bacteriorhodopsin.
AB  - Bacteriorhodopsin is a protein found in cell membranes of the organism H.
      salinarum, where it functions as an efficient light-driven proton pump. Because
      bacteriorhodopsin is one of the simplest ion pumps known in biology, it has been
      the subject of intensive investigations over the last three decades, using
      methods spanning the range from femtosecond spectroscopy and crystallography to
      biochemistry and molecular biology. Here, we focus on the structural basis for
      the function of this protein, with primary emphasis on the contributions of
      electron microscopy and crystallography towards unravelling the mechanism of
      vectorial proton pumping.

PMID- 12804284
TI  - Phase recovery and lensless imaging by iterative methods in optical, X-ray and
      electron diffraction.
AB  - Thomas Young's quantitative analysis of interference effects provided the
      confidence needed to revive the wave theory of light, and firmly established the
      concept of phase in optics. Phase plays a similarly fundamental role in matter
      wave interferometry, for which the field-emission electron microscope provides
      ideal instrumentation. The wave-particle duality is vividly demonstrated by
      experimental 'Young's fringes' using coherent electron beams under conditions in
      which the flight time is less than the time between particle emission. A brief
      historical review is given of electron interferometry and holography, including
      the Aharonov-Bohm effect and the electron Sagnac interferometer. The simultaneous
      development of phase-contrast imaging at subnanometre spatial resolution has
      greatly deepened our understanding of atomic processes in biology, materials
      science and condensed-matter physics, while electron holography has become a
      routine tool for the mapping of electrostatic and magnetic fields in materials on
      a nanometre scale. The encoding of phase information in scattered farfield
      intensities is discussed, and non-interferometric, non-crystallographic methods
      for phase retrieval are reviewed in relationship to electron holography. Examples
      of phase measurement and diffraction-limited imaging using the hybrid input
      output iterative algorithm are given, including simulations for soft X-ray
      imaging, and new experimental results for coherent electron and visible-light
      scattering. Image reconstruction is demonstrated from experimental electron and
      visible-light Fraunhofer diffraction patterns. The prospects this provides for
      lensless imaging using particles for which no lenses exist (such as neutrons,
      condensates, coherent atom beams and X-rays) are discussed. These new
      interactions can be expected to provide new information, perhaps, for example, in
      biology, with the advantage of less damage to samples.

PMID- 12804285
TI  - Electron interference: mystery and reality.
AB  - Interference of electron waves has developed from a fascinating phenomenon in
      basic physics to a key method for the highly sophisticated investigation of both
      electric and magnetic structures in solid-state materials. After more than 20
      years of development, electron holography in the transmission electron microscope
      is now a very powerful technique for the analysis of micro-fields down to atomic
      dimensions. The applications extend from highly sensitive measurements in
      semiconductor technology to the quantitative characterization of atomic
      structures.

PMID- 12804286
TI  - Neutrino oscillations.
AB  - The wave theory of light, and in particular the principle of interference, was
      formulated by Thomas Young in 1801. In the 20th century, the principle of
      interference was extended to the quantum mechanical wave functions describing
      matter. The phenomenon of quantum mechanical interference of different neutrino
      states, neutrino oscillations, has provided one of the most exciting developments
      in high energy particle physics of the last decade. Observations of the flavour
      oscillations of neutrinos produced by distant sources, such as from the core of
      the Sun, provide compelling evidence that neutrinos have mass. This article
      describes the main features and the most significant experimental observations of
      this unusual application of the principle of interference.

PMID- 12804287
TI  - Construction of a high-resolution moire interferometer for investigating
      microstructural displacement fields in materials.
AB  - A high-magnification moire interferometer has been constructed with a spatial
      resolution of the order of 1 microm to measure the local in-plane displacement
      field associated with a material's microstructure. Laser illumination passes
      through phase-stepping optics and is delivered to the microscope head by
      polarization-preserving single-mode optical fibres. The head itself is a compact
      unit consisting of collimating optics, an objective lens and a charge coupled
      device (CCD) camera. Thin-phase gratings are cast onto the sample surface with a
      compliant epoxy resin and coated with ca. 5 nm of gold to enhance the fringe
      contrast and reduce speckle noise. By switching between the laser illumination
      and white-light illumination, the underlying microstructure is viewed in exact
      registration with the measured displacement fields. The application of the
      instrument is illustrated here by visualization of displacement fields in polymer
      bonded explosives (PBXs) during deformation to failure. PBXs are highly filled
      polymers consisting of up to 95% by weight crystalline explosive bound in a
      variety of polymeric binders. The mechanical properties of PBXs are highly
      dependent on the microstructure, and moire interferometry is an ideal tool for
      investigating the relationship between the 1-100 microm sized crystals and the
      displacement fields. Methods such as this are required if computer models of
      inhomogeneous materials are to be accurately validated.

PMID- 12804288
TI  - A review of recent work in sub-nanometre displacement measurement using optical
      and X-ray interferometry.
AB  - This paper reviews recent work in the field of displacement measurement using
      optical and X-ray interferometry at the sub-nanometre level of accuracy. The
      major sources of uncertainty in optical interferometry are discussed and a
      selection of recent designs of ultra-precise, optical-interferometer-based,
      displacement measuring transducers presented. The use of X-ray interferometry and
      its combination with optical interferometry is discussed.

PMID- 12804289
TI  - The application of interferometry to optical astronomical imaging.
AB  - In the first part of this review we survey the role optical/infrared
      interferometry now plays in ground-based astronomy. We discuss in turn the
      origins of astronomical interferometry, the motivation for its development, the
      techniques of its implementation, examples of its astronomical significance, and
      the limitations of the current generation of interferometric arrays. The second
      part focuses on the prospects for ground-based astronomical imaging
      interferometry over the near to mid-term (i.e. 10 years) at optical and near
      infrared wavelengths. An assessment is made of the astronomical and technical
      factors which determine the optimal designs for imaging arrays. An analysis based
      on scientific capability, technical feasibility and cost argues for an array of
      large numbers of moderate-sized (2 m class) telescopes rather than one comprising
      a small number of much larger collectors.

PMID- 12804290
TI  - Interference effects in femtosecond spectroscopy.
AB  - This article aims to provide a short synopsis of interference effects connected
      with ultrafast laser pulses, where 'ultrafast' is defined as ca. 100 fs or
      faster. The discussion is divided into three parts: the first shows how
      interference between waves is responsible for generation of light pulses in the
      femtosecond and attosecond time domains; the second describes characterization of
      ultrafast pulses by different interferometric techniques, including diffraction
      of femtosecond light by a double slit; and the final section discusses selected
      measurements of interference phenomena created and probed with femtosecond time
      resolution, with an emphasis on experiments in atomic physics. The article
      attempts to illustrate how wave-like interference is a unifying concept that
      pervades much of physics on a femtosecond time-scale.

PMID- 12804291
TI  - Exuberant interference: rainbows, tides, edges, (de)coherence...
AB  - Young's pioneering studies of interference have led to fundamental developments
      in wave physics. Supernumerary rainbows were the first example of diffraction
      associated with caustics. Cotidal lines (connecting places where the tide is high
      at a given time) were the first example of wavefronts in the modern sense
      (pattern of phase contours (arg psi(1) + psi(2)) of the superposition of waves
      psi(1) and psi(2), rather than the superposed patterns of the separate phases arg
      psi(1) and arg psi(2)), and led to the discovery of phase singularities. Edge
      diffracted waves extend the range of asymptotic methods applied to waves and
      continue to find diverse and unexpected applications. Young's understanding of
      the conditions for observing interference are now part of decoherence theory,
      which explains, for example, the emergence of the classical world from the
      quantum world.

PMID- 12804292
TI  - Time-resolved diffraction and interference: Young's interference with photons of
      different energy as revealed by time resolution.
AB  - We present time-resolved diffraction and two-slit interference experiments using
      a streak camera as a detector for femtosecond pulses of photons. These
      experiments show how the diffraction pattern is built by adding frames of a few
      photons to each frame. It is estimated that after 300 photons the diffraction
      pattern emerges. With time resolution we can check the speed of light and put an
      upper limit of 2 ps at our resolution to the time for wave function collapse in
      the quantum measurement process. We then produce interference experiments with
      photons of different energies impinging on the slits, i.e. we know which photon
      impinges on each slit. We show that for poor time resolution, no interference is
      observed, but for high time resolution, we have interference that is revealed as
      beats of 100 GHz frequency. The condition for interference is that the two pulses
      should overlap spatially at the detector, even if the pulses have different
      energies but are generated from the same pulse of the laser. The interference
      seems to be in agreement with classical theory at first sight. However, closer
      study and analysis of the data show deviations in the visibility of the
      interference fringes and of their phase. These experiments are discussed in
      connection with quantum mechanics and it may be concluded that the time
      resolution provides new data for understanding the longstanding and continuing
      arguments on wave-particle duality initiated by Newton, Young, Fresnel, Planck
      and others. A thought experiment is presented in the appendix to try to
      distinguish the photons at the detector by making it sensitive to colour.

PMID- 12804293
TI  - Young's experiment and the finiteness of information.
AB  - Young's experiment is the quintessential quantum experiment. It is argued here
      that quantum interference is a consequence of the finiteness of information. The
      observer has the choice of whether that information manifests itself as path
      information or in the interference pattern or partly in both to the extent
      defined by the finiteness of information.

PMID- 12804295
TI  - Have sudden large releases of methane from geological reservoirs occurred since
      the Last Glacial Maximum, and could such releases occur again?
AB  - Methane emissions from geological reservoirs may have played a major role in the
      sudden events terminating glaciation, both at the start of the Bolling/Allerod
      and also at the end of the Younger Dryas. These reservoirs include Arctic methane
      hydrates and also methane hydrate stored in offshore marine sediments in tropical
      and temperate latitudes. Emissions from hydrate stores may have resonated with
      tropical wetland emissions, each reinforcing the other. Because methane is such a
      powerful greenhouse gas, much smaller emissions of methane, compared with carbon
      dioxide, are required in order to have the same short-term impact by climate
      forcing. The methane-linked hypothesis has much geological support from sea-floor
      evidence of emission. However, Greenland ice-core records have been interpreted
      as showing methane as a consequential factor, rather than the leader, of change.
      This interpretation can be challenged on the grounds that temperature gradients
      in Greenland ice record local changes and local timing of a step-like shift in
      weather fronts, while methane concentrations record changes on a hemispheric and
      global scale. There are large remaining hydrate reservoirs in the Arctic and in
      shelf sediments globally, and there is substantial risk of further emissions.

PMID- 12804296
TI  - The alkenone-CO2 proxy and ancient atmospheric carbon dioxide.
AB  - Cenozoic climates have varied across a variety of time-scales, including slow,
      unidirectional change over tens of millions of years, as well as severe,
      geologically abrupt shifts in Earth's climatic state. Establishing the history of
      atmospheric carbon dioxide is critical in prioritizing the factors responsible
      for past climatic events, and integral in positioning future climate change
      within a geological context. One approach in this pursuit uses the stable carbon
      isotopic composition of marine organic molecules known as alkenones. The
      following report represents a summary of the factors affecting alkenone carbon
      isotopic compositions, the underlying assumptions and accuracy of short- and long
      term CO(2) records established from these sedimentary molecules, and their
      implications for the controls on the evolution of Cenozoic climates.

PMID- 12804297
TI  - The carbon isotope composition of ancient CO2 based on higher-plant organic
      matter.
AB  - Carbon isotope ratios in higher-plant organic matter (delta(13)C(plant)) have
      been shown in several studies to be closely related to the carbon isotope
      composition of the ocean-atmosphere carbon reservoir, and, in particular, the
      isotopic composition of CO(2). These studies have primarily been focused on
      geological intervals in which major perturbations occur in the oceanic carbon
      reservoir, as documented in organic carbon and carbonates phases (e.g. Permian
      Triassic and Triassic-Jurassic boundary, Early Toarcian, Early Aptian, Cenomanian
      Turonian boundary, Palaeocene-Eocene Thermal Maximum (PETM)). All of these
      events, excluding the Cenomanian-Turonian boundary, record negative carbon
      isotope excursions, and many authors have postulated that the cause of such
      excursions is the massive release of continental-margin marine gas-hydrate
      reservoirs (clathrates). Methane has a very negative carbon isotope composition
      (delta(13)C, ca. 60 per thousand ) in comparison with higher-plant and marine
      organic matter, and carbonate. The residence time of methane in the ocean
      atmosphere reservoir is short (ca. 10 yr) and is rapidly oxidized to CO(2),
      causing the isotopic composition of CO(2) to become more negative from its
      assumed background value (delta(13)C, ca. -7 per thousand ). However, to date,
      only the Early Toarcian, Early Aptian and PETM are well-constrained chronometric
      sequences that could attribute clathrate release as a viable cause to create such
      rapid negative delta(13)C excursions. Notwithstanding this, the isotopic analysis
      of higher-plant organic matter (e.g. charcoal, wood, leaves, pollen) has the
      ability to (i) record the isotopic composition of palaeoatmospheric CO(2) in the
      geological record, (ii) correlate marine and non-marine stratigraphic
      successions, and (iii) confirm that oceanic carbon perturbations are not purely
      oceanographic in their extent and affect the entire ocean-atmosphere system. A
      case study from the Isle of Wight, UK, indicates that the carbon isotope
      composition of palaeoatmospheric CO(2) during the Mid-Cretaceous had a background
      value of 3 per thousand, but fluctuated rapidly to more positive (ca. +0.5 per
      thousand ) and negative values (ca. 10 per thousand ) during carbon cycle
      perturbations (e.g. carbon burial events, carbonate platform drowning, large
      igneous province formation). Hence, fluctuations in the carbon isotope
      composition of palaeoatmospheric CO(2) would compromise our use of palaeo-CO(2)
      proxies that are dependent on constant carbon isotope ratios of CO(2).

PMID- 12804298
TI  - Carbon dioxide and climate over the past 300 Myr.
AB  - The link between atmospheric CO(2) levels and global warming is an axiom of
      current public policy, and is well supported by physicochemical experiments, by
      comparative planetary climatology and by geochemical modelling. Geological tests
      of this idea seek to compare proxies of past atmospheric CO(2) with other proxies
      of palaeotemperature. For at least the past 300 Myr, there is a remarkably high
      temporal correlation between peaks of atmospheric CO(2), revealed by study of
      stomatal indices of fossil leaves of Ginkgo, Lepidopteris, Tatarina and
      Rhachiphyllum, and palaeotemperature maxima, revealed by oxygen isotopic
      (delta(18)O) composition of marine biogenic carbonate. Large and growing
      databases on these proxy indicators support the idea that atmospheric CO(2) and
      temperature are coupled. In contrast, CO(2)-temperature uncoupling has been
      proposed from geological time-series of carbon isotopic composition of palaeosols
      and of marine phytoplankton compared with foraminifera, which fail to indicate
      high CO(2) at known times of high palaeotemperature. Failure of carbon isotopic
      palaeobarometers may be due to episodic release of CH(4), which has an unusually
      light isotopic value (down to -110 per thousand, and typically -60 per thousand
      delta(13)C) and which oxidizes rapidly (within 7-24 yr) to isotopically light
      CO(2). Past CO(2) highs (above 2000 ppmv) were not only times of catastrophic
      release of CH(4) from clathrates, but of asteroid and comet impacts, flood basalt
      eruptions and mass extinctions. The primary reason for iterative return to low
      CO(2) was carbon consumption by hydrolytic weathering and photosynthesis, perhaps
      stimulated by mountain uplift and changing patterns of oceanic thermohaline
      circulation. Sequestration of carbon was promoted in the long term by such
      evolutionary innovations as the lignin of forests and the sod of grasslands,
      which accelerated physicochemical weathering and delivery of nutrients to fuel
      oceanic productivity and carbon burial.

PMID- 12804299
TI  - Comparison of clay mineral stratigraphy to other proxy palaeoclimate indicators
      in the Mesozoic of NW Europe.
AB  - This paper reviews the opportunities and pitfalls associated with using clay
      mineralogical analysis in palaeoclimatic reconstructions. Following this,
      conjunctive methods of improving the reliability of clay mineralogical analysis
      are reviewed. The Mesozoic succession of NW Europe is employed as a case study.
      This demonstrates the relationship between clay mineralogy and palaeoclimate.
      Proxy analyses may be integrated with clay mineralogical analysis to provide an
      assessment of aridity-humidity contrasts in the hinterland climate. As an
      example, the abundance of kaolinite through the Mesozoic shows that, while
      interpretations may be difficult, the Mesozoic climate of NW Europe was subject
      to great changes in rates of continental precipitation. We may compare
      sedimentological (facies, mineralogy, geochemistry) indicators of
      palaeoprecipitation with palaeotemperature estimates. The integration of clay
      mineralogical analyses with other sedimentological proxy indicators of
      palaeoclimate allows differentiation of palaeoclimatic effects from those of sea
      level and tectonic change. We may also observe how widespread palaeoclimate
      changes were; whether they were diachronous or synchronous; how climate, sea
      level and tectonics interact to control sedimentary facies and what palaeoclimate
      indicators are reliable.

PMID- 12804300
TI  - Cryptic species of planktonic foraminifera: their effect on palaeoceanographic
      reconstructions.
AB  - Shells of planktonic foraminifera recovered from marine sediments provide a
      multitude of important palaeoproxies. Most of these proxies are based on the
      assumption that each morphospecies of planktonic foraminifera represents a
      genetically continuous species with a unique habitat. Recent discovery of
      hitherto hidden genetic diversity among modern planktonic foraminifera has
      significant repercussions on palaeoproxies derived from their fossil shells. We
      have compiled all available data on this genetic diversity. To date, 33 cryptic
      genetic types were found in 9 out of the 22 sequenced morphospecies of modern
      planktonic foraminifera. An examination of this database suggests that cryptic
      genetic diversity may be a prevalent pattern among modern planktonic
      foraminifera, but that the total number of cryptic genetic types per
      morphospecies is not large and that most genetic types show a non-random pattern
      of distribution in the oceans. Using modern distribution data from the Atlantic
      Ocean as constraints, the relationship between abundances of three genetic types
      of Globigerina bulloides and sea-surface temperature has been modelled and this
      model has been applied to a database of species counts in Atlantic coretops (761
      samples). Trials with artificial neural networks (ANNs), the modern analogue
      technique and Imbrie-Kipp transfer functions showed that the splitting of G.
      bulloides into three genetic types resulted in substantial reduction in the
      prediction error rate (by 5 to 34%) and that this improvement was by far greatest
      in ANN trials (on average more than 20%). We conclude that such a large reduction
      in error rate occurred because the models resonated with a real pattern in the
      original data. This study indicates that genetic diversity among planktonic
      foraminifera may become more of a gift than malaise to palaeoproxies. If it
      becomes possible to distinguish these genetic types in the fossil record, the
      accuracy of proxies based on planktonic foraminifera will indeed substantially
      increase.

PMID- 12804301
TI  - Potential and limitations of Sr/Ca ratios in coccolith carbonate: new
      perspectives from cultures and monospecific samples from sediments.
AB  - The Sr/Ca ratio of coccoliths was recently proposed as a potential indicator of
      past growth rates of coccolithophorids, marine algae, which play key roles in
      both the global carbonate and carbon cycles. We synthesize calibrations of this
      proxy through laboratory culture studies and analysis of monospecific coccolith
      assemblages from surface sediments. Cultures of coccolithophorids Helicosphaera
      carteri, Syracosphaera pulchra and Algirospira robusta confirm a 1-2% increase in
      Sr/Ca per degrees C previously identified in Emiliania huxleyi and Gephyrocapsa
      oceanica. This effect is not due merely to increases in growth rate with
      temperature and must be considered in palaeoceanographic studies. In light
      limited cultures of E. huxleyi, Calcidiscus leptoporus and G. oceanica at
      constant temperature, coccolith Sr/Ca ratios vary by 10% across the range of
      possible growth and calcification rates for a given species. Among different
      species under similar culture conditions, Sr/Ca ratios vary by 30%. Although the
      highest ratios are in the cells with highest calcification and organic carbon
      fixation rates, at lower rates there is much scatter, indicating that different
      mechanisms control interspecific and intraspecific coccolith Sr/Ca variations. In
      field studies in the Equatorial Pacific and Somalia coastal region, coccolith
      Sr/Ca correlates with upwelling intensity and productivity. A more dynamic
      response is observed in larger coccoliths like C. leptoporus (23-55% variation in
      Sr/Ca) than in smaller coccoliths of G. oceanica or Florisphaera profunda (6-15%
      variation in Sr/Ca). This response suggests that, despite temperature effects,
      coccolith Sr/Ca has potential as an indicator of coccolithophorid productivity.
      If the variable Sr/Ca response of different species accurately reflects their
      variable productivity response to upwelling (and not different slopes of Sr/Ca
      with productivity), coccolith Sr/Ca could provide useful data on past changes in
      coccolith ecology. The mechanism of coccolith Sr/Ca variations remains poorly
      understood but is probably more closely tied to biochemical cycles during carbon
      acquisition than to chemical kinetic effects on Sr incorporation in the calcite
      coccolith crystals.

PMID- 12804302
TI  - Luminescence intensity in coral skeletons from Mona Island in the Caribbean Sea
      and its link to precipitation and wind speed.
AB  - This study investigates the potential of using changes of interannual
      luminescence intensity in hermatypic Montastraea coral skeletons in the
      northeastern Caribbean as a proxy of precipitation and (trade) wind speed. In
      order to find wavelength pairs that are well suited to detect variations in the
      concentration of incorporated terrestrial humic substances in coral skeletons,
      and thus to reconstruct past run-off and rainfall, three-dimensional excitation
      emission matrix fluorescence spectra of seawater samples were investigated on
      their relationships to local precipitation. Three prominent excitation-emission
      peaks at 310/430, 425/480 and 390/530 nm were identified. The fluorescence
      intensities of the wavelength pair 310/430 nm showed a weak relationship, while
      the wavelength pairs at 425/480 and 390/530 nm showed strong relationships with
      local precipitation. Variations in luminescence intensities from scans on the
      coral surface along the growth axis using the wavelengths identified were then
      compared with instrumental records of regional precipitation and wind speed. In
      the coral skeleton as well, the wavelength pairs at 425/480 and 390/530 nm were
      more strongly correlated with regional precipitation and wind speed. This
      indicates that these two wavelength pairs are well suited to reconstruct past
      precipitation and wind speed. In order to evaluate the use as a proxy of trade
      wind variability in the Caribbean, tropical Atlantic region, variations in
      luminescence intensity were compared with a record of trade wind variability from
      the southern Caribbean. The two records are strongly correlated, which suggests
      that luminescence intensity in coral skeletons, at least from Mona Island, can be
      used as proxy of trade wind variability and precipitation.

PMID- 12804303
TI  - Towards a European tephrochronological framework for Termination 1 and the Early
      Holocene.
AB  - The record of deposition of tephras in Europe and the North Atlantic during the
      period 18.5-8.0 (14)C ka BP (the Last Termination and Early Holocene) is
      reviewed. Altogether, 34 tephras originating from four main volcanic provinces
      (Iceland, the Eifel district, the Massif Central and Italy) have been identified
      so far in geological sequences spanning this time-interval. Most of the records
      have been based, until very recently, on observations of visible layers of
      tephras. Here, we report on the potential for extending the areas over which some
      of the tephras can be traced by the search for layers of micro-tephra, which are
      not visible to the naked eye, and on the use of geochemical methods to correlate
      them with known tephra horizons. This approach has greatly extended the area in
      Northern Europe over which the Vedde Ash can be traced. The same potential exists
      in southern Europe, which is demonstrated for the first time by the discovery of
      a distinct layer of micro-tephra of the Neapolitan Yellow Tuff in a site in the
      Northern Apennines in Italy, far to the north of the occurrences of visible
      records of this tephra. The paper closes by considering the potential for
      developing a robust European tephrostratigraphy to underpin the chronology of
      records of the Last Termination and Early Holocene, thereby promoting a better
      understanding of the nature, timing and environmental effects of the abrupt
      climatic changes that characterized this period.

PMID- 12804304
TI  - Strontium and osteoporosis.

PMID- 12804307
TI  - Biochemical markers of bone turnover and fracture prediction.
AB  - Low bone mineral density is a strong risk factor for fractures in the older
      woman. Biochemical markers of bone turnover may predict fracture risk
      independently of bone mineral density. High levels of bone resorption markers are
      associated with increased risk of fracture in both retrospective and prospective
      studies, although the evidence for bone formation markers and fracture risk is
      equivocal. For example, the risk of fracture is increased up to two-fold in women
      with elevated levels of several markers of bone resorption. Prediction models
      have been developed to predict the 10-year risk of fracture using bone mineral
      density and biochemical markers of bone turnover and these could prove very
      useful in clinical practice.

PMID- 12804309
TI  - Learning disabilities and the menopause.
AB  - How menopause affects women with learning disabilities is a neglected area of
      research. Women with learning disabilities experience the same physiological
      effects of the menopause as others, including hot flushes and night sweats, but
      difficulties in understanding and communication mean that additional supports are
      often required. They are less likely to report the psychological difficulties or
      symptoms associated with menopause than women in the general population.
      Menopause is usually earlier in women with learning disability and earlier still
      for those with Down's syndrome. Debate about hormone replacement therapy often
      ignores the needs of women with learning disabilities who, as a result, are very
      often excluded from the decision-making process. Physical problems among women
      with learning disabilities and other aspects of ageing warrant particular focus.

PMID- 12804308
TI  - Dietary phytoestrogens and bone health.
AB  - The role of soy phytoestrogens in preserving bone health has to date not been
      studied in large randomised controlled studies. These bioactive naturally
      occurring compounds are viewed as potential selective oestrogen receptor
      modulators based on their structural similarity to oestradiol, in vitro
      mechanisms of action and hormonal effects in human subjects. Much of the evidence
      for a role in bone health has stemmed from animal data, as most of the available
      human studies are of short duration and have used either bone biomarkers or bone
      mineral density as end point measures. However, recent data from a long-term
      study suggest these compounds have a bone conserving effect in menopausal women
      but to accurately examine the relative importance of these compounds for bone
      health in postmenopausal women an assessment of consumption on fracture rates
      will be critical.

PMID- 12804310
TI  - Molecular genetics and endometrial cancer.
AB  - Endometrial cancer is a common gynaecological malignancy in the industrialised
      world. Unopposed stimulation of the endometrium by oestrogens is the classic
      aetiological factor associated with the development of this malignancy. However,
      not all are associated with oestrogen exposure and two different
      clinicopathological types can be distinguished: the oestrogen-related of
      endometrioid type (type I) and the non-oestrogen-related of non-endometrioid type
      (mainly papillary serous or clear cell carcinomas) (type II). Recent advances in
      the knowledge on the molecular genetics of endometrial cancer have shown that the
      molecular changes involved in its the development differ in oestrogen-dependent
      type I and non-oestrogen-dependent type II. Type I carcinomas frequently show
      mutations of DNA-mismatch repair genes (MLH1, MSH2, MSH6), PTEN, k-ras and beta
      catenin genes whereas type II malignancies are characterised by aneuploidy, p53
      mutations and her2/neu amplification. This article reviews the latest findings
      concerning common gene mutations involved in the development and progression of
      endometrial cancer.

PMID- 12804311
TI  - The use of food supplements among women attending menopause clinics in the West
      Midlands.
AB  - OBJECTIVE: To estimate the extent of use of over the counter food supplements in
      women attending menopause clinics in the West Midlands. STUDY DESIGN:
      Questionnaire survey of women attending menopause clinics in Solihull Hospital,
      Birmingham Heartlands Hospital, Rugby and Walsgrave Hospitals and Birmingham
      Women's Hospital. MAIN OUTCOME MEASURES: Type and rate of use of food supplements
      in hormone replacement therapy (HRT) users and nonusers and perceived benefits.
      RESULTS: Three hundred and forty women completed the questionnaire. 95% (n = 326)
      belonged to the white European ethnic group. The median age was 53 years, with
      50% (n = 170) in the 50-59 years age group, and 30 % (n = 95) in the age range 40
      49 years. Overall use of over the counter supplements in the clinic was 43% (n =
      147), with Oil of Evening Primrose (53%) and vitamins (44%) being the most
      commonly used preparations. 71% (n = 242) women were users of conventional HRT.
      Of these, 46% were also using food supplements. The use of food supplements was
      higher amongst HRT users (46%) as compared to non-HRT users (32%). The use was
      similar between smokers and non-smokers. The most commonly perceived benefit was
      a feeling of well-being, 39% (n = 58/147). The proportionate use was highest in
      social class I and class II (51% and 54% respectively), in keeping with amount of
      disposable income. Friends (27%), the internet (26%) and magazines (20%) were the
      most commonly quoted sources of information. 79% (n = 116/147) were spending up
      to  10 each month on alternative remedies. 10% (n = 14/147) of women were
      visiting practitioners of alternative remedies. CONCLUSIONS: The use of food
      supplements is widespread and particularly in those already taking conventional
      HRT. This study was not designed to test confidence in orthodox medicine, but the
      prevalence of use of supplements amongst menopausal women attending menopause
      clinics. The most commonly perceived benefit is a feeling of well-being, but
      users of food supplements are unsure of any additional benefit when supplements
      are taken in conjunction with conventional therapy. There is a misapprehension
      that "herbal" or "natural" equals safe. In addition, the correlation between
      supplement use and side effects is very seldom made, as these compounds are
      mistakenly considered almost universally safe, and physicians often fail to
      enquire about their use in routine history taking.

PMID- 12804313
TI  - Menorrhagia in the menopause.

PMID- 12804312
TI  - Comparison of the effect of progesterone, medroxyprogesterone acetate and
      norethisterone on the proliferation of human breast cancer cells.
AB  - OBJECTIVE: To investigate in vitro the influence of the three most used
      progestogens in continuous combined HRT on cell proliferation of the human breast
      cancer cell line MCF-7. STUDY DESIGN: Progesterone (P), medroxyprogesterone
      acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM
      to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation
      was measured after seven days using the ATP-chemosensitivity test. RESULTS: P
      alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and
      NET displayed a significant inhibition of cell proliferation between 20 and 25%
      for MPA and 23 and 41% for NET over the whole concentration range tested. The
      effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination
      with oestradiol, P still significantly reduced cell proliferation, the values
      being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was
      found, whereas for NET the values were between 23 and 38%. CONCLUSIONS: Our in
      vitro results indicate that the influence on breast cancer risk using HRT in
      postmenopausal women may depend on the type of progestogen used as well as on the
      regimen applied. However, the inhibitory in vitro net effect of the progestogens
      at clinically relevant dosages is rather minimal and it remains uncertain as to
      whether progestogens generally may reduce breast cancer risk in long-term
      treatment. Further clinical trials are urgently required to determine the
      appropriate choice - if any - of progestogen to complement HRT.

PMID- 12804314
TI  - Always take a full history.

PMID- 12804317
TI  - Hormone replacement therapy: where are we now?

PMID- 12804315
TI  - MRC brings WISDOM study to a premature close.

PMID- 12804318
TI  - The national randomised trial of hormone replacement therapy in women with a
      history of early stage breast cancer: an update.

PMID- 12804320
TI  - Symptom reporting at menopause: a review of cross-cultural findings.
AB  - Extensive cross-cultural and comparative research reveals that the majority of
      women do not find the menopausal transition a difficult time. This research also
      shows considerable variation in symptom reporting at the end of menstruation. It
      is argued that socio/cultural variables, including language usage and
      expectations about the menopausal experience, do not fully account for these
      differences, and that biological variation must also be taken into account. In
      those societies where subjective reporting of symptoms, including vasomotor
      symptoms, is low, such findings should not be dismissed as the result of learned
      cultural expectations that mask reality.

PMID- 12804321
TI  - Changes in body composition at menopause--age, lifestyle or hormone deficiency?
AB  - One of the major concerns of perimenopausal women is obesity-and for a good
      reason. Both general and abdominal obesity as well as loss of skeletal muscle
      (sarcopenia) are accelerated through the menopausal transition and lifestyle
      changes as well as sex hormone deficiency play important roles. Most well
      conducted clinical trials have demonstrated hormone replacement therapy induced
      reversal or at least impairment of menopausal changes in body composition and the
      common worry that it causes weight gain is unsubstantiated. Coaching of weight
      loss in obese individuals is often a frustrating task but is nevertheless of
      immense importance because of the health hazards of obesity. Through the
      climacteric period, short-term hormone replacement therapy, with or without
      androgens for preservation of muscle mass, might inhibit obesity and this is
      likely to boost motivation for introduction of more comprehensive and long
      lasting initiatives linked to persistent weight loss and long-term health
      benefit.

PMID- 12804322
TI  - Statins and menopausal health.
AB  - Cardiovascular disease is associated with high morbidity and mortality.
      Cholesterol-lowering statins can reduce health risks both in men and women. While
      this benefit has thus far been attributed to the lipid-lowering effects of these
      drugs, the importance of their direct actions on vascular tissue is gaining more
      recognition. Furthermore, recent studies suggest that statins might also be
      effective in preventing osteoporosis and Alzheimer's disease. Equally interesting
      are experimental results showing that statins may inhibit growth of certain
      malignancies such as the breast. When statins are combined with hormone
      replacement therapy (HRT), even greater beneficial effects on the lipid profile
      can be obtained. To our knowledge we have investigated for the first time direct
      vascular effects by combining statins with HRT. We were able to identify
      significant beneficial effects on endothelial function and vascular smooth muscle
      proliferation. In the context of current discussions on the benefits and risks of
      HRT in treating patients with pre-existing cardiovascular disease, it appears
      particularly important that interventional studies should be conducted to
      evaluate the therapeutic relevance of statin/HRT combinations. At present, this
      is the most important conclusion drawn from the data collected thus far on the
      combination of these two drug types. There is some evidence suggesting drug
      specific effects, particularly adverse reactions and statin interactions, which
      should be considered when using this combination therapy.

PMID- 12804323
TI  - Management of hot flushes without oestrogen.
AB  - Hot flushes are probably the most common symptom resulting in medical
      consultation in relation to the menopause. The association between the two is so
      strong that the connection is often invoked even when hot flushes occur in a
      regularly menstruating woman. Oestrogen significantly reduces hot flushes but is
      not used by all women-either because of contraindications or a reluctance to take
      oestrogen-based therapy. In addition, hot flushes may persist in spite of
      adequate oestrogen replacement, and physicians are often faced with the dilemma
      of finding something instead of, or in addition to, oestrogen for symptom relief.
      The available alternatives for the management of hot flushes are reviewed.

PMID- 12804324
TI  - Homeopathy and the menopause.
AB  - Significant numbers of patients in developed countries use complementary,
      alternative, or unconventional medicine. Homeopathy is one of the most widespread
      and controversial of these therapies and has been used for over 150 years. There
      are two main theoretical tenets: the principle of "similars" and the use of
      dilutions called "potencies". The principle of "similars" states that patients
      with particular signs and symptoms can be cured if given a drug that produces the
      same signs and symptoms in a healthy individual. The second principle is that
      remedies retain biological activity if they are repeatedly diluted and agitated
      or shaken between each dilution. Data from case histories, observational studies
      and uncontrolled trials suggest that the homeopathic approach can offer a
      clinically relevant choice for women with menopausal symptoms and those with
      breast cancer whether they are taking tamoxifen or not. Randomised controlled
      trials are being conducted to investigate this potential benefit.

PMID- 12804325
TI  - No increased risk of endometrial hyperplasia with fixed long-cycle hormone
      replacement therapy after two years.
AB  - The appropriate dose of progestogen during long-cycle hormone replacement is
      still under debate. We present preliminary two-year results from an open five
      year clinical trial of 132 postmenopausal women. All subjects had long-cycle HRT
      consisting of 70 days 2 mg oestradiol valerate (E(2)V), followed by 14 days 2 mg
      E(2)V plus 20 mg medroxyprogesterone acetate, and a seven-day hormone-free
      period. No endometrial samples with hyperplasia or indicative of malignancy were
      found at 24 months.

PMID- 12804326
TI  - Hormone replacement therapy and fibroids.

PMID- 12804327
TI  - Intuition.

PMID- 12804328
TI  - The prevalence and predictors of psychological distress in men with prostate
      cancer who are seeking support.
AB  - OBJECTIVE: The incidence of prostate cancer has risen sharply in the last decade,
      yet knowledge about the psychological health of men with this disease is still
      limited. A study was therefore undertaken to identify (1) the prevalence of
      psychological distress in these males, and (2) factors predicting psychological
      distress. DESIGN: Retrospective cross-sectional survey design by means of a self
      administered questionnaire. METHOD: A sample of 94 men with various stages of
      prostate cancer completed the Functional Assessment of Cancer Therapy-Prostate
      Instrument (FACT-P), the Hospital Anxiety Depression Scale (HADS) and items
      measuring satisfaction with medical care. RESULTS: We detected a prevalence rate
      of 38% of participants reporting psychological distress corresponding to a HADS
      cut-off score at or above 15. A standard multivariate regression analysis
      revealed social/family well-being, physical well-being and functional well-being
      as significant inverse predictors of psychological distress. CONCLUSIONS: Health
      professionals should be aware of the potential for psychological distress in
      patients exhibiting poor physical functioning and those with apparent deficits in
      social or family support in this under-studied group of patients. Strategies for
      psychosocial intervention are implied.

PMID- 12804329
TI  - Body dissatisfaction, dieting awareness and the impact of parental influence in
      young children.
AB  - OBJECTIVES: This study aimed to assess the level of body dissatisfaction and
      dieting awareness in young children. METHOD: A sample of 135 children aged
      between 5 and 8 years old were individually interviewed. Body dissatisfaction was
      assessed by means of figure preference ratings, and dieting awareness by
      responses to a brief scenario. RESULTS: The difference between boys' ratings of
      current and ideal figures was not significant at any age; nor was that of 5-year
      old girls. However, 6-, 7- and 8-year-old girls rated their ideal figure as
      significantly thinner than their current figure. For dieting awareness there was
      no significant gender effect, although level of dieting awareness increased with
      age. Multiple regression analyses showed that body dissatisfaction was predicted
      by gender and perception of mothers' body dissatisfaction, while age was the only
      significant predictor of dieting awareness. CONCLUSIONS: A substantial proportion
      of young children have internalized societal beliefs concerning the ideal body
      shape and are well aware of dieting as a means for achieving this ideal. In
      particular, the desire for thinness emerges in girls at around age 6.

PMID- 12804330
TI  - Social problem-solving abilities and distress among family members assuming a
      caregiving role.
AB  - We examined the relation of social problem-solving abilities to distress
      experienced by family members assuming a caregiving role for a loved one who had
      recently incurred a severe physical disability. Family members completed measures
      of problem-solving, depression and health, while their loved one participated in
      an inpatient rehabilitation programme. Correlational analyses indicated that a
      negative problem orientation was significantly predictive of caregiver distress,
      regardless of the degree of physical impairment of the care recipient. Women
      reported more distress on several measures than men, and disability severity was
      also associated with depression and impaired social functioning. Family members
      with a greater negative orientation may be at risk to develop psychological and
      health problems upon assuming a caregiver role. These results are discussed in
      light of theoretical models of social problem-solving, and implications are
      presented for psychological interventions and for health policy concerning family
      caregivers and their care recipients.

PMID- 12804331
TI  - The psychosocial impact of the implantable cardioverter defibrillator: a meta
      analytic review.
AB  - OBJECTIVE: The implantable cardioverter defibrillator (ICD) has become the
      treatment of choice for ventricular arrhythmia (VA; abnormal heart rhythms) and
      the prevention of sudden cardiac death (SCD). Recent clinical trials have shown
      the ICD to be superior to anti-arrhythmic medication in reducing mortality;
      however, research has suggested that ICD recipients experience poor psychosocial
      adjustment following implantation of the device. This aim of this study was to
      identify the key psychological characteristics associated with ICD implantation
      and to establish whether poor psychosocial outcome can be attributed directly to
      the device and its therapy. METHOD: Studies which reported valid and reliable
      measures of psychological functioning in ICD patients and appropriate comparison
      groups were considered for inclusion in a meta-analytic review. A systematic
      search of electronic databases and reference lists identified 20 studies which
      fulfilled the inclusion criteria. RESULTS: There were no significant differences
      in psychosocial outcome between ICD patients and drug-maintained VA patients or
      between pre- and post-implant ICD patients. However, ICD patients reported
      significantly worse psychological functioning and physical functioning than other
      cardiac controls. CONCLUSION: These findings suggest that poor psychosocial
      outcome in ICD patients may occur as a result of variables associated with the
      underlying VA condition, rather than as a direct response to implantation of the
      device and its therapy. This holds important implications for the development and
      implementation of psychological interventions for patients experiencing VA, in
      preference to ICD-specific programmes.

PMID- 12804332
TI  - Re-appraising HIV testing: an exploration of the psychosocial costs and benefits
      associated with learning one's HIV status in a purposive sample of Scottish gay
      men.
AB  - OBJECTIVE: This study explored contemporary understandings of the psychosocial
      costs and benefits associated with learning one's HIV status within a purposive
      sample of Scottish gay men. It seeks to provide insight into the psychosocial
      factors associated with decision-making processes relating to the HIV antibody
      test. METHOD: Transcripts of one-to-one interviews (N = 19) and four focus groups
      (N = 18) were analysed using Interpretative Phenomenological Analysis.
      Participants had varied HIV testing histories, and the sample included men who
      identified their HIV status as positive, men who identified it as negative, and
      men who did not know. RESULTS: The HIV test could resolve doubt and anxiety for
      some men, but only when 'not knowing' was experienced as less tolerable than an
      imagined positive result. Many participants were deterred from seeking an HIV
      test because of their fears of the implications of a positive result. The
      decision to take an HIV test could be understood as a choice between living with
      uncertainty and the perceived impact of ascertaining HIV status. CONCLUSION: For
      the participants in this study, the decision to test or not involved many complex
      medical, psychological and social factors. It is argued that the development of
      HIV testing policy must start with a perspective grounded in an understanding and
      appreciation of these complexities.

PMID- 12804333
TI  - Experimental evidence for interpretive but not attention biases towards somatic
      information in patients with chronic fatigue syndrome.
AB  - OBJECTIVE: This study tested whether CFS patients have an attentional information
      processing bias for illness-related information and a tendency to interpret
      ambiguous information in a somatic fashion. DESIGN: 25 patients meeting research
      criteria for a diagnosis of CFS were compared to 24 healthy matched controls on a
      modified Stroop task and an ambiguous cues task. METHOD: In the modified Stroop
      task, participants colour named a series of somatic, depressed and neutral words
      in order to ascertain whether the somatic words were more distracting to the CFS
      patients than the depressed and neutral words when compared to controls. In the
      ambiguous cues task, participants were presented with a tape-recorded list of 30
      words including 15 ambiguous illness words (e.g., vein/vain) and 15 unambiguous
      words. For each word, they were asked to write down the first word that came into
      their head. A somatic bias score was obtained for each subject by summing the
      number of somatic responses to the ambiguous word cues. RESULTS: Although CFS
      patients were significantly slower in colour naming all of the Stroop word
      categories than controls, there was no evidence for illness or depressed words
      creating greater interference than neutral words. However, on the ambiguous cues
      task, CFS patients made significantly more somatic interpretations than controls
      and this bias was significantly associated with the extent to which they
      currently reported symptoms. CONCLUSION: CFS patients have an interpretive bias
      for somatic information which may play a part in the maintenance of the disorder
      by heightening patients' experience of physical symptoms and helping to maintain
      their negative illness schemas. Although patients did not show an attentional
      bias in this study, this may be related to the methodology employed.

PMID- 12804334
TI  - Illness perceptions, mood and coping in predicting attendance at cardiac
      rehabilitation.
AB  - OBJECTIVE: The aim of this study was to identify psychological variables in
      poor/non-attendance at cardiac rehabilitation (CR). We investigated whether
      attenders and poor/non-attenders differed in relation to components of the self
      regulatory model and coping, and which of these variables were the best
      predictors of attendance behaviour. DESIGN: A cross-sectional, between groups
      design was employed. In contrast with two previous similar studies, participants
      completed self-report measures shortly before the start date for the CR
      programme. Univariate and logistic regression analyses were conducted. METHOD: In
      all, 93 individuals who had been invited to attend CR completed the Illness
      Perceptions Questionnaire (IPQ), the Hospital Anxiety and Depression Scale (HADS)
      and the Coping Orientation to Problems Experienced (COPE). Subsequently, 32
      participants failed to attend, or dropped out early from, the programme. RESULTS:
      Attenders differed from poor/non-attenders in that they perceived a greater
      number of symptoms and consequences of their illness, greater distress, less
      strong beliefs that their illness had been caused by a germ or virus, and used
      problem-focused and emotion-focused coping more frequently. The best predictors
      of poor/non-attendance were lower perceptions of symptoms and
      controllability/curability of illness, and less frequent use of problem-focused
      and more frequent use of maladaptive coping strategies. CONCLUSION: Attenders and
      poor/non-attenders at CR were distinguished by illness representations, distress
      and usage of coping strategies. The variables found to be the best predictors of
      attendance could be used to screen those unlikely to attend and to develop
      interventions for enhancing attendance.

PMID- 12804335
TI  - Repressive coping style and positive self-presentation.
AB  - OBJECTIVE: This paper reviews 59 studies looking at cognitive, individual
      differences and physiological correlates of the repressive coping style, as
      defined by Weinberger, Schwartz, and Davidson (1979). A central aim is to
      evaluate the relative importance of the anxiety and social desirability
      components of repression. Thus, the empirical study investigates the
      relationships between repression and a number of relevant, but hitherto
      unexamined, constructs, including trait emotional intelligence (trait EI), self
      estimated intelligence, functional and dysfunctional impulsivity, and stoicism.
      It was hypothesized that repressors would score higher than the other three
      groups on trait EI, self-estimated IQ and functional impulsivity, but lower on
      dysfunctional impulsivity. METHOD: In total, 259 (174 females) participants from
      three British universities completed questionnaires measuring the dependent and
      independent variables. Participants were divided into four groups (truly low
      anxious, non-defensive/high anxious, defensive/high anxious and repressors) based
      on their scores on anxiety and social desirability. Analyses (moderated multiple
      regressions and ANOVAs) were conducted both on the total sample as well as on
      'extreme-scoring' individuals. RESULTS: Where there were significant differences,
      the hypotheses were supported, particularly with respect to trait EI, self
      estimated IQ and impulsivity. Using 'extreme-scoring' groups did not effectively
      change the results. The regressions revealed an absence of significant
      interactions between anxiety and social desirability. CONCLUSION: Results are
      discussed in terms of the now replicated effect that repressors present a highly
      positive and optimistic self-image, despite cognitive and behavioural data
      suggesting that their coping style is psychologically unhealthy. In addition, it
      is argued that many findings in the repressive coping style literature can be
      parsimoniously explained through main effects of anxiety or social desirability
      alone (i.e., without invoking a construct that combines the two).

PMID- 12804337
TI  - Observations from the CDC: Monitoring women's health in the United States:
      selected chronic disease indicators, 1991-2001 BRFSS.
AB  - OBJECTIVES: This analysis considers factors that underlie the leading causes of
      death and disability for adult women in the United States and changes in those
      factors over the previous decade. METHODS: 1991-2001 Behavioral Risk Factor
      Surveillance System (BRFSS) data are used to review changes over the decade in
      the most important indicators of women's health. Estimates are weighted by
      demographic characteristics and selection probabilities. Sample sizes ranged from
      50,875 women in 1991 to 121,456 in 2001. RESULTS: State-level maps show dramatic
      changes in obesity prevalence over the previous decade. Obesity prevalence
      increased to 21.5% in 2001 from 12.4% in 1991. Reports of exercise, never
      smoking, and binge drinking remained essentially level. The percentage of women
      who currently smoke cigarettes declined slightly but significantly. Reports of
      ever being told they had high blood pressure increased significantly for women
      aged > or =65 years. There was a significant and substantial change in the
      percentage of women aged > or =40 who reported having a mammogram in the past 2
      years (62.7% in 1991, 76.2% in 2001). CONCLUSIONS: Findings show that we are at a
      critical juncture in public health. Some changes are stunning (e.g., rising
      obesity), others remain stubbornly static (e.g., smoking), and still others
      demonstrate positive trends (e.g., mammogram screening). The increase in obesity
      foretells similar future increases in obesity-related chronic conditions unless
      public health efforts can stem the tide. It is imperative that effective
      strategies to change behavior are developed, especially those that are women
      focused, to improve quality and length of life.

PMID- 12804338
TI  - Toward optimal health: the experts discuss the routine care of women with cancer.
      Interview by Jodi Meisler.

PMID- 12804339
TI  - Does the Y chromosome make a difference? Gender differences in attempts to change
      cardiovascular disease risk factors.
AB  - PURPOSE: The purpose of this study was to determine if gender differences exist
      in attempts to change cardiovascular disease (CVD) risk factor behaviors,
      specifically cigarette smoking, sedentary lifestyle, and overweight, and if the
      success of these attempted behavior changes also differs by gender in the
      Pawtucket Heart Health Program (PHHP). METHODS: The risk factors were considered
      in reference to individuals who needed to change a particular risk factor
      behavior. Data were gathered from three different sources within the PHHP (the
      contact card registry of participants and both cross-sectional and cohort
      household surveys). RESULTS: Women were much more likely than men to participate
      in PHHP risk factor programs related to smoking, exercise, or weight loss. Women
      were also more likely than men to self-report making attempts to change these
      risk factor behaviors. Men self-reported to have a greater percentage of long
      term smoking cessation success than women, although men and women had similar
      success rates related to weight loss and increasing physical activity. Men who
      reported being at least 20% overweight at baseline achieved significantly greater
      self-reported weight loss when followed up about 8.5 years later than women who
      were overweight at baseline. CONCLUSIONS: More research needs to be done to find
      ways to help women become more successful at modifying CVD risk factor behaviors.
      In addition, emphasis must be placed on ways to help men initiate and increase
      the number of attempts they make to change these same risk factor behaviors.

PMID- 12804340
TI  - Anorexia nervosa medical issues.
AB  - Anorexia nervosa is an increasingly common chronic psychiatric disorder with a
      multitude of medical complications. Most of these complications are reversible if
      there is timely restoration of body weight. A few of them, particularly
      osteoporosis, refeeding complications, and cardiac arrhythmia, are potentially
      much more serious. In the end, a multidisciplinary team approach with input from
      a primary care provider who is familiar with these medical sequelae, together
      with psychiatric and dietary expertise, can effectuate a successful outcome.

PMID- 12804341
TI  - Hormone replacement therapy and the risk of incident congestive heart failure:
      the Cardiovascular Health Study.
AB  - BACKGROUND: The development of congestive heart failure (CHF) in older persons is
      related to a variety of mechanisms. Hormone replacement therapy (HRT) affects
      several of the pathways that may be important in the development of CHF. We
      hypothesized that HRT would be associated with a decreased risk of incident CHF.
      METHODS: Using Cox proportional-hazards regression, we assessed the risk of
      incident CHF (n = 304) associated with time-dependent past and current use of HRT
      compared to never use. The Cardiovascular Health Study is a prospective cohort
      study of community-dwelling adults aged 65 years and older. This analysis
      included female participants without a history of CHF at baseline (n = 3223).
      RESULTS: At baseline, 62% were never users, 26% were past users, and 12% were
      current users of HRT. Compared with never users, the multivariable relative risk
      (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users
      and 1.34 (0.93,1.94) for current users. Results were similar among most treatment
      and clinical subgroups, except that the association of current HRT with CHF
      appeared to depend on body mass index (BMI) or osteoporosis status. The RR was
      0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women,
      and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the
      RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for
      women without osteoporosis (p = 0.001 for interaction). CONCLUSIONS: Overall, HRT
      was not associated with the risk of incident CHF, although BMI and osteoporosis
      appeared to modify the association of HRT with CHF. The risk of CHF was lower in
      patients with lower BMI or osteoporosis.

PMID- 12804342
TI  - Baseline health-related quality of life in postmenopausal women with coronary
      heart disease: the Estrogen Replacement and Atherosclerosis (ERA) trial.
AB  - OBJECTIVES: This study examined the baseline health-related quality of life
      (HRQL) of 301 postmenopausal women with heart disease enrolled in the Estrogen
      Replacement and Atherosclerosis (ERA) trial. METHODS: The primary measure of HRQL
      was the Medical Outcomes Study Short Form-36 (MOS SF-36). The SF-36 was augmented
      with secondary assessments, including measures of depressive symptoms, life
      satisfaction, urinary incontinence, sleep disturbance, and physical symptoms.
      Multiple regression analyses were used to test hypotheses regarding the
      contribution of positive (social support) and negative (social strain) aspects of
      social relations after accounting for other correlates of HRQL and heart disease.
      RESULTS: Results indicate that social support was positively associated with
      better functioning for all measured outcomes (all p < 0.05) except symptom
      frequency and severity. Social strain was negatively associated with HRQL
      functioning (all p < 0.05) except overall physical functioning, sleep
      disturbance, and urinary incontinence. In addition, several comorbid conditions
      were negatively associated with HRQL outcomes. In particular, chest pain was
      significantly associated with worse functioning on all HRQL outcomes except
      urinary incontinence. CONCLUSIONS: These data suggest that both clinical status
      variables (particularly chest pain) and the psychosocial context (represented by
      dimensions of relationship quality) influenced HRQL in this cohort. Thus,
      interventions that combine medical treatments with psychosocially based
      interventions may be most effective for women at risk for impaired HRQL.

PMID- 12804343
TI  - Women smokers' perceptions of smoking-related health risks.
AB  - OBJECTIVE: Unrealistic perceptions of personal susceptibility to the health
      hazards of smoking may be an important determinant of cigarette smoking and a
      barrier to smoking cessation. This study was undertaken to assess perceptions of
      smoking-related health risks among women smokers. METHODS: A secondary analysis
      was conducted using cross-sectional data collected from 1184 (response rate 61%)
      perimenopausal women patients from one university-affiliated health system.
      RESULTS: The majority of respondents were white and college-educated and had an
      annual household income of over $60,000. Twelve percent of respondents were
      current smokers, 37% were former smokers, and 51% were never smokers. Sixty
      percent of current smokers rated their lifetime risk for developing heart disease
      or lung cancer as average or below average, and 75% of current smokers rated
      their lifetime risk for developing osteoporosis as average or below average.
      Multivariable logistic regression analysis revealed that any smoking history
      (past or current) was associated with perception of above average risk for
      developing lung cancer, but only heavier smoking (> or =10 cigarettes per day)
      was associated with perception of above average risk for developing heart
      disease. No level of smoking was associated with perception of above average risk
      for developing osteoporosis. CONCLUSIONS: The majority of women smokers surveyed
      perceived their lifetime risk for developing heart disease, lung cancer, and
      osteoporosis as average or below average. It appears that women smokers are more
      aware of their increased risk for developing lung cancer than their increased
      risk for developing heart disease or osteoporosis.

PMID- 12804344
TI  - Depressive symptoms among pregnant women screened in obstetrics settings.
AB  - OBJECTIVES: This study aimed to describe the prevalence of depressive
      symptomatology during pregnancy when seen in obstetric settings, the extent of
      treatment in this population, and specific risk factors associated with mood
      symptoms in pregnancy. METHODS: A total of 3472 pregnant women age 18 and older
      were screened while waiting for their prenatal care visits in 10 obstetrics
      clinics using a brief (10 minute) screening questionnaire. This screen measured
      demographics, tobacco and alcohol (TWEAK problem alcohol use screening measure),
      and depression measures, including the Center for Epidemiological Studies
      Depression scale (CES-D), use of antidepressant medications, past history of
      depression, and current treatment (i.e., medications, psychotherapy, or
      counseling) for depression. RESULTS: Of women screened, 20% (n = 689) scored
      above the cutoff score on the CES-D, and only 13.8% of those women reported
      receiving any formal treatment for depression. Past history of depression, poorer
      overall health, greater alcohol use consequences, smoking, being unmarried,
      unemployment, and lower educational attainment were significantly associated with
      symptoms of depression during pregnancy. CONCLUSIONS: These data show that a
      substantial number of pregnant women screened in obstetrics settings have
      significant symptoms of depression, and most of them are not being monitored in
      treatment during this vulnerable time. This information may be used to justify
      and streamline systematic screening for depression in clinical encounters with
      pregnant women as a first step in determining which women may require further
      treatment for their mood symptoms. As elevations in depressive symptomatology
      have been associated with adverse maternal and infant outcomes, further study of
      the impact of psychiatric treatment in gravid women is essential.

PMID- 12804345
TI  - Improved fitness narrows the symptom-reporting gap between older men and women.
AB  - PURPOSE: Functional differences between the sexes are well documented. The causes
      of functional decline are complex, but in general, women report more functional
      decline and have a greater prevalence of disabling chronic conditions than do
      men. The role of exercise training in attenuating functional decline has not been
      studied extensively. Therefore, the purpose of this study was to compare sex
      differences in adaptations to exercise training in measures of physical function
      (physical performance and self-report) and symptom reporting. METHODS: Men and
      women (n = 114, ages 65-90) performed purely aerobic exercises (walking or
      stationary cycling) or a combination of aerobic plus spinal flexibility exercises
      for 1 hour 3 days a week for 3 months in a supervised, hospital-based setting.
      Outcome measures assessed in a blinded fashion at baseline and 3 months included
      physical performance (10-meter walk time, timed bed mobility, 360-degree turn
      time), self-reported physical function and disability (Nagi and Rosow-Breslau
      disability questions and SF-36 Physical Function Scale), and symptoms (number of
      symptoms, pain, shortness of breath, fatigue, and muscle weakness). RESULTS: At
      baseline, men had better physical performance scores and fewer functional
      limitations and reported fewer symptoms than women. Following exercise training,
      women, but not men, improved in most measures of physical function and reported
      fewer symptoms. The absence of change among the men is most likely due to ceiling
      effect measures of physical function among the men. CONCLUSIONS: We conclude that
      among functionally impaired women, exercise training has a positive effect on
      physical disability and symptom reporting. Exercise training attenuated the gap
      in self-reported symptoms between men and women in this study.

PMID- 12804346
TI  - Healthcare access and utilization by patients infected with human
      immunodeficiency virus: does gender matter?
AB  - OBJECTIVE: To examine access to and utilization of primary healthcare services
      with respect to gender. Greater family and child-rearing responsibilities are
      possible barriers to healthcare access and utilization for women with HIV
      infection. METHODS: This study was part of a prospective, randomized, controlled
      trial evaluating primary care for HIV-infected patients at Duke University
      Medical Center (DUMC), a tertiary care medical center. Subjects were 214 HIV
      infected, uninsured or publicly insured participants. Ambulatory care visits,
      emergency room utilization, hospitalization rates, length of stay, preventive and
      screening measures, and antiretroviral use were the outcome measures. RESULTS:
      Women (n = 83) and men (n = 131) enrolled in the study were similar with respect
      to race, educational level, marital status, and employment status. Women with HIV
      were more likely than men to have children (80% vs. 25%, p = 0.001) and spend
      their time as primary caregivers for their children (22% vs. 0.8%, p = 0.001).
      Women had higher CD4(+) cell counts (378 +/- 287 vs. 243 +/- 252 cells/microl, p
      = 0.0002), and a smaller proportion of women than men had AIDS at baseline (41%
      vs. 62%, p = 0.002). Women and men had similar numbers of primary care visits,
      emergency room visits, annual admission rates, and lengths of stay for
      hospitalizations. Pneumocystis carinii pneumonia prophylaxis, pneumococcal
      vaccination, and tuberculosis screening were also similar between women and men.
      Women were more likely than men to have ever been prescribed an antiretroviral
      agent (88.0% vs. 71.8%, p = 0.005). CONCLUSIONS: Women had greater familial
      responsibilities than men, but this was not a barrier to access or utilization of
      healthcare services. Despite less advanced HIV disease, women received similar
      care and had similar utilization of health services.

PMID- 12804347
TI  - Characteristics and outcomes for women physicians who work reduced hours.
AB  - OBJECTIVES: To understand the characteristics of women physicians who work
      reduced hours in dual-earner couples and how such work schedules affect the
      quality of the marital role, parental role, and job role, as well as indicators
      of psychological distress, burnout, career satisfaction, and life satisfaction.
      METHODS: Survey of a random sample of female physicians between 25 and 50 years
      of age, working within 25 miles of Boston, whose names were obtained from the
      Registry of Board Certification in Medicine in Massachusetts. Interviewers
      conducted a 60-minute face-to-face close-ended interview after a 20-minute mailed
      questionnaire had been completed. RESULTS: Fifty-one full-time physicians and 47
      reduced-hours physicians completed the study, for a completion rate of 49.5%.
      There was no difference in age, number of years as a physician, mean household
      income, number of children, or presence of an infant in the home between reduced
      hours and full-time physicians. Reduced-hours physicians, however, were more
      likely to be in a generalist specialty (40% vs. 12%, p = 0.001) and to spend a
      greater portion of their time in patient care (64.5% vs. 50.1%, p = 0.003) and
      less time in research (4.9% vs. 18.0%, p = 0.002) than full-time physicians. In
      addition, there was no difference between the two groups in the perception of
      work interfering with family life (1.8 vs. 1.7, p = 0.17; scale 1-7 with 7 high)
      or family life interfering with work (1.4 vs. 1.5, p = 0.62). Physicians who
      worked their preferred number of hours (25% of full-time and 57% of reduced-hours
      physicians), regardless of full-time (self-reported hours 35-90 hours per week)
      or reduced-hours (20-60 hours per week) status, reported better job role quality
      (r = 0.35, p = 0.001), schedule fit (r = 0.41, p < or = 0.001), lower burnout (r
      = -0.22, p = 0.03), better marital role quality (r = 0.28, p = 0.006), and higher
      life satisfaction (r = 0.29, p = 0.005). CONCLUSIONS: Women physicians who work
      their preferred number of hours achieve the best balance of work and family
      outcomes.

PMID- 12804348
TI  - Abstracts of the 11th Annual Congress on Women's Health. Hilton Head Island,
      South Carolina, USA. May 31-June 3, 2003.

PMID- 12804350
TI  - Evaluation of a two-part survey item to assess moderate physical activity: the
      Cross-Cultural Activity Participation Study.
AB  - PURPOSE: This study evaluated a two-part survey item that assessed adherence to
      the national moderate physical activity (MPA) recommendation (>/=30 min/day on
      >/=5 days/week). METHODS: Participants were African American (n = 137), Native
      American (n = 129), and Caucasian (n = 50) women >/= 40 years from South Carolina
      and New Mexico, who were participating in a study validating physical activity
      surveys. The survey item was compared with data obtained from MPA recorded in PA
      records (min/day), Caltrac accelerometers (Muscle Dynamics, Torrance, CA)
      (kcal/day), and pedometers (steps/day). RESULTS: Approximately 64% of the
      participants reported meeting the MPA recommendation on the survey item. Adjusted
      analyses showed that those who reported meeting the recommendation were more
      active than those who reported not meeting the recommendation (109.2 vs. 83.9
      min/day, 2171.2 vs. 2088.4 kcal/day, and 5795.7 vs. 4797.2 steps/day,
      respectively; all p < 0.0001). The types of activities recorded in the PA record
      did not differ by self-reported adherence to the MPA recommendation except for
      walking (25.2 vs. 14.0 min/day for those who reported meeting vs. not meeting the
      recommendation, respectively; p < 0.05). A higher proportion of those who
      reported meeting the recommendation also reported participating in conditioning
      activities compared with those who reported not meeting the recommendation (31%
      vs. 19%, respectively; p < 0.05). CONCLUSIONS: The two-part survey item can
      reliably differentiate between higher and lower levels of activity. Those who
      perceive themselves as meeting the MPA recommendation are, on average, likely to
      have higher activity levels than those who perceive that they do not meet the
      recommendation.

PMID- 12804351
TI  - Trends in use of medications associated with women's ambulatory care visits.
AB  - BACKGROUND: Data from the CDC's National Health Care Survey (NHCS) can assist
      researchers studying women's healthcare utilization. METHODS: Using data from the
      National Ambulatory Medical Care Survey (NAMCS) and the National Hospital
      Ambulatory Medical Care Survey (NHAMCS), component surveys of the NHCS, this
      paper presents prescribing trends from 1995 to 2000 for the 10 therapeutic drug
      classes of medications mentioned most often during women's ambulatory care
      visits. RESULTS: Antidepressants top the list as the most frequently mentioned
      therapeutic class in 1999-2000, followed by estrogens and progestins,
      antiarthritics, and drugs for acid/peptic disorders. The number of medications
      prescribed increased by about 13% during visits by women to physicians' offices
      and hospital outpatient departments between 1995-1996 and 1999-2000, from 144 to
      162 mentions per 100 visits, respectively. CONCLUSIONS: Researchers can use the
      NHCS to track changes in use over time and to target potential issues related to
      access to care, quality of care, or cost that warrant further, in-depth study.

PMID- 12804352
TI  - Toward optimal health: the experts discuss fitness among baby boomers. Interview
      by Jodi Godfrey Meisler.

PMID- 12804353
TI  - Breast cancer and human immunodeficiency virus infection: issues for the 21st
      century.
AB  - BACKGROUND: As we enter the 21st century, AIDS and breast cancer are two pressing
      issues in women's health. The spread of AIDS continues unabated. More than 21.8
      million people have died of AIDS, and it is estimated that as of December 2000 an
      additional 36.1 million people, mostly in sub-Saharan Africa, were infected with
      the human immunodeficiency virus. In addition, women now constitute almost one
      half of all AIDS cases. With the widespread use of highly active antiretroviral
      therapy in the United States, the overall health and survival of HIV(+)
      individuals has improved dramatically. Thus, as the HIV(+) population matures, we
      will be called on to diagnose and treat more cases of breast cancer in
      seropositive women. What can we expect as the incidence of these two diseases
      begins to overlap? METHODS: Medline search, and review of the relevant
      literature. RESULTS: Forty-six published cases of breast cancer in HIV(+)
      individuals identified. CONCLUSIONS: Based on epidemiologic data from Western
      countries and Africa, HIV infection is not permissive for breast cancer. This is
      reflected in the paucity of available data. Early reports consisted of case
      reports, describing advanced cancers with unusual presentations and uniformly
      poor prognoses. Recent series describe more favorable prognoses and long-term
      survivors. It appears that hormonal therapy is well tolerated and effective, even
      in cases of locally advanced disease, and the toxicity from standard chemotherapy
      regimens is unacceptably high.

PMID- 12804354
TI  - STaT: a three-question screen for intimate partner violence.
AB  - OBJECTIVE: To develop a simple, sensitive screening tool for lifetime intimate
      partner violence (IPV) in women. METHODS: In the emergency department (ED) of an
      urban teaching hospital, 75 English-speaking women between 18 and 64 years old
      were tested. The sensitivity and specificity of 43 dichotomous response-option,
      IPV screening questions were compared. The reference standard was lifetime IPV,
      determined by a semistructured interview, using preset criteria of specific
      violence acts or emotional control or both by an intimate partner. Questions with
      high sensitivity (>70%) were tested together against the reference standard.
      Answering yes to any question scored 1 point. Content area and the area under
      receiver-operator curve (AUROC) of the screening questions determined the final
      tool. RESULTS: Sixty-three percent of women reported lifetime IPV. Eight of the
      43 screening questions had a sensitivity of >70%. After testing possible
      combinations, the final three-question screen, STaT had the highest AUROC. The
      STaT questions are: "Have you ever been in a relationship where your partner has
      pushed or Slapped you?" "Have you ever been in a relationship where your partner
      Threatened you with violence?" and "Have you ever been in a relationship where
      your partner has thrown, broken or punched Things?" The sensitivity (95%
      confidence intervals [95% CI]) of STaT for lifetime IPV is 96% (90%, 100%), 89%
      (81%, 98%), and 64% (50%, 78%) for a score of >/=1, >/=2, and 3, respectively.
      The corresponding specificity is 75% (59%-91%), 100%, and 100%. CONCLUSIONS:
      Three simple questions when used together can effectively identify lifetime IPV
      and will aid clinicians' efforts to identify abuse in women.

PMID- 12804355
TI  - Factors that influence the decision to undergo cosmetic breast augmentation
      surgery.
AB  - BACKGROUND: This study examined the factors that motivate women to seek cosmetic
      breast augmentation surgery. METHODS: Twenty-five breast augmentation surgery
      candidates completed measures of body image dissatisfaction, sociocultural
      influences on physical appearance, marital and sexual satisfaction, and self
      report questionnaires that assessed other motivations for surgery. Thirty
      physically similar women who were not interested in breast augmentation also
      completed the measures. RESULTS: Replicating previous studies, breast
      augmentation candidates, compared with controls, reported greater dissatisfaction
      with their breasts. The two groups, however, did not differ on overall body image
      dissatisfaction or greater awareness or internalization of sociocultural
      influences on physical appearance. Breast augmentation patients reported more
      positive sexual functioning compared with controls. CONCLUSIONS: Overall, breast
      augmentation patients appeared to be motivated by their feelings about their
      breasts rather than direct or indirect influence from external sources, such as
      romantic partners or sociocultural representations of beauty. These findings
      provide new information on the motivations behind breast augmentation and dispute
      several stereotypes about the factors that influence the pursuit of this surgery.

PMID- 12804356
TI  - A pilot study of treatment of bacterial vaginosis with a buffering vaginal
      microbicide.
AB  - BACKGROUND: Bacterial vaginosis (BV) is an extremely common problem for women and
      is associated with adverse pregnancy outcomes and HIV infection. Currently
      available antibiotic treatments are moderately effective but may need to be
      repeated frequently because of the recurrent nature of the disease. We undertook
      a pilot study of a buffering vaginal microbicide in the treatment of BV. METHODS:
      Women with clinically diagnosed BV were recruited to receive seven applications
      (5 g per application) of BufferGel trade mark (ReProtect, LLC, Baltimore, MD), a
      topical vaginal microbicide, and had clinical and gram stain evaluation of
      response. Subjects were evaluated at 2-3 days after the last application of
      BufferGel as a test of cure and again at 1 month to assess for relapse. Subjects
      with BV at test of cure were offered oral metronidazole. RESULTS: Thirty-one
      women were screened, 16 were offered enrollment, and 10 completed the study.
      Treatment with BufferGel was clinically effective in 70% of women at 2-3 days
      after treatment and in 40% of women by 1-month follow-up. CONCLUSIONS: These
      results suggest that 5 g of BufferGel vaginally once a day appears to be a
      moderately effective treatment for BV.

PMID- 12804357
TI  - Another round in the mammography controversy.
AB  - PURPOSE: The October 2001 publication of a meta-analysis questioning the
      scientific basis for recommending screening mammography sparked yet a new flame
      of controversy about this issue. We conducted a national survey in March 2002 to
      provide information about women's perspectives on the issues, including the
      evidence regarding the efficacy of mammography and, ultimately, their intentions
      to continue screening. METHODS: We added 12 questions to a national telephone
      omnibus survey in March 2002 to assess women's reactions to the ongoing debate.
      Responses were collected over three waves of the twice-weekly survey to obtain
      data from 733 women between the ages of 40 and 69. The sample was weighted to the
      U.S. population for census region, age, race, ethnicity, and educational
      attainment. RESULTS: Consistent with prior studies, most women were getting
      regular mammograms (78%) (95% confidence interval [CI] 75%-81%), >90% believed
      that mammography is effective in detecting breast cancer (95%) (95% CI 93%-97%)
      and in reducing breast cancer mortality (93%) (95% CI 91%-96%), and only about
      22% (95% CI 19%-25%) said they were confused. Logistic regression analyses
      revealed sociodemographic differences among women who had heard about the
      controversy and who reported some confusion about mammograms. Women with lower
      levels of education, younger women, and those residing in nonmetropolitan areas
      were significantly less likely to be aware of the controversy. Although a
      majority of women said they were not confused about mammography, minority women
      and women with lower education levels were more likely to report being confused.
      There were no significant demographic differences in intentions to get future
      mammograms. Women who were concerned about getting breast cancer were much more
      likely to be planning to have future mammograms than women who were not at all
      concerned (odds ratio [OR] 3.63; 95% CI 2.37, 5.56). Likewise, respondents who
      said that they had enough information to make decisions whether to get future
      mammograms were much more likely to plan on getting screened than women who said
      they did not have enough information (OR 2.47; 95% CI 1.14, 5.40). CONCLUSIONS:
      These results do not suggest that controversy leads to lower rates of adherence.
      They do indicate that some women lack the information needed to make informed
      decisions about mammography.

PMID- 12804358
TI  - Differences in perceptions of risk, benefits, and barriers by stage of
      mammography adoption.
AB  - PURPOSE: The purpose of this report was to identify the relationship of
      mammography adoption with perceived susceptibility to breast cancer and perceived
      benefits and barriers to mammography. METHODS: Stage of mammography adoption was
      based on the Transtheoretical Model. Previously validated scales for
      susceptibility, benefits, and barriers were administered. The sample included 694
      women who were recruited from a large Health Maintenance Organization and general
      medicine clinic. The mean age was 61.2 years; 30% were African American and 67%
      were Caucasian. RESULTS: Women who were currently compliant (action) had lower
      perceived barriers than other groups. Precontemplators and Relapse
      Precontemplators had lower perceived benefits scores than those who were
      currently compliant or those who were thinking of having a mammogram. Women who
      had never received a mammogram were more likely to feel they were too old for the
      procedure. Stage matched interventions are discussed. CONCLUSIONS: Beliefs differ
      among women in various stages of mammography adoption. These differences may
      inform interventions to increase mammography use.

PMID- 12804359
TI  - The correlations between estradiol, estrone, estriol, progesterone, and sex
      hormone-binding globulin and anterior cruciate ligament stiffness in healthy,
      active females.
AB  - BACKGROUND: Injury to the anterior cruciate ligament (ACL) often requires surgery
      and extensive rehabilitation. Women who participate in collegiate sports and
      military drills are more likely to injure their ACL than are men participating in
      similar activities. The influence of the normal fluctuation of sex hormones on
      the physical properties of the ACL is one potential cause for this disparity. The
      purpose of this study was to report the correlation between estradiol, estrone,
      estriol, progesterone, and sex hormone binding globulin (SHBG) and ACL stiffness
      during three phases of the menstrual cycle in normally cycling, healthy females.
      METHODS: We tested ACL stiffness and collected blood from 20 female subjects who
      were not using oral contraception during three phases of their menstrual cycle.
      Ligament stiffness was tested with the KT-2000 trade mark knee arthrometer
      (MEDmetric, San Diego, CA). Concentrations of estradiol and SHBG were assessed
      via radioimmunoassay (RIA). Progesterone, estriol, and estrone concentrations
      were determined via enzyme-linked immunoassay. RESULTS: Spearman rank correlation
      analysis indicated a significant correlation between estradiol concentration and
      ACL stiffness (-0.70, p < 0.001) and estrone concentration and ACL stiffness near
      ovulation (0.46, p = 0.040). With the effects of the other variables controlled,
      there was a significant partial correlation between estradiol (-0.80, p < 0.001),
      estriol (0.70, p = 0.003), and progesterone (0.66, p = 0.005) and ACL stiffness
      near ovulation. CONCLUSIONS: Our results indicate that there is a significant
      correlation between estradiol, estriol, and progesterone and ACL stiffness
      suggesting that fluctuating levels of sex hormones may influence the stiffness of
      the ACL near ovulation. Future studies that examine the relationship between sex
      hormones and the physical properties of the ACL should be focused near the
      ovulation phase of the menstrual cycle.

PMID- 12804362
TI  - Bombardment of the Hadean Earth: wholesome or deleterious?
AB  - Graham Ryder died in January 2002 at the age of 53. He was a Staff Scientist at
      the Lunar and Planetary Science Institute in Houston, TX for most of his
      professional life, studying lunar petrology and planetary impacts. For many years
      he was the senior editor of the Proceedings of the Lunar and Planetary Science
      Conference, and he was the senior editor of Geological Society of America Special
      Paper 307, The Cretaceous-Tertiary Event and Other Catastrophes in Earth History.
      He was the major advocate for the 3.8 Ga lunar impact cataclysm and was just
      beginning to publish on correlations of the early lunar impact record to that of
      the other inner planets at the time of his death. Graham's abstract to the Rubey
      Colloquium was never presented. Although Graham made many of the points in this
      abstract to lunar science audiences, he certainly would have wanted these views
      to be shared with the Astrobiology community. We have taken the liberty of
      publishing this abstract with the Rubey proceedings, with only a few minor
      revisions to include reference to some recently published papers. These revisions
      were recommended by Gary R. Byerly, who reviewed this abstract for publication.

PMID- 12804363
TI  - Spherule beds 3.47-3.24 billion years old in the Barberton Greenstone Belt, South
      Africa: a record of large meteorite impacts and their influence on early crustal
      and biological evolution.
AB  - Four layers, S1-S4, containing sand-sized spherical particles formed as a result
      of large meteorite impacts, occur in 3.47-3.24 Ga rocks of the Barberton
      Greenstone Belt, South Africa. Ir levels in S3 and S4 locally equal or exceed
      chondritic values but in other sections are at or only slightly above background.
      Most spherules are inferred to have formed by condensation of impact-produced
      rock vapor clouds, although some may represent ballistically ejected liquid
      droplets. Extreme Ir abundances and heterogeneity may reflect element
      fractionation during spherule formation, hydraulic fractionation during
      deposition, and/or diagenetic and metasomatic processes. Deposition of S1, S2,
      and S3 was widely influenced by waves and/or currents interpreted to represent
      impact-generated tsunamis, and S1 and S2 show multiple graded layers indicating
      the passage of two or more wave trains. These tsunamis may have promoted mixing
      within a globally stratified ocean, enriching surface waters in nutrients for
      biological communities. S2 and S3 mark the transition from the 300-million-year
      long Onverwacht stage of predominantly basaltic and komatiitic volcanism to the
      late orogenic stage of greenstone belt evolution, suggesting that regional and
      possibly global tectonic reorganization resulted from these large impacts. These
      beds provide the oldest known direct record of terrestrial impacts and an
      opportunity to explore their influence on early life, crust, ocean, and
      atmosphere. The apparent presence of impact clusters at 3.26-3.24 Ga and
      approximately 2.65-2.5 Ga suggests either spikes in impact rates during the
      Archean or that the entire Archean was characterized by terrestrial impact rates
      above those currently estimated from the lunar cratering record.

PMID- 12804364
TI  - Petrographic criteria for recognizing certain types of impact spherules in well
      preserved precambrian successions.
AB  - Impact spherule layers in sedimentary successions can open a new window on large
      impacts to complement the better-known record of terrestrial craters. At least
      six spherule layers have been found in well-preserved late Archean to
      Paleoproterozoic strata, and a growing body of geochemical evidence indicates
      they are impact ejecta. The most distinctive characteristics of these impact
      spherules are: (1) a predominance of highly spherical grains; (2) the presence of
      grains with unusual shapes such as teardrops and dumbbells; (3) fibroradial
      aggregates of K-feldspar crystals nucleated on the edges of spherules; and (4)
      clear internal spots representing both cement-filled vesicles and replaced glass
      cores, which, in contrast to the nuclei of ooids and armored lapilli, are not
      always located in the centers of the spherules. These characteristics permit the
      reliable differentiation of these impact spherules from spheroidal particles of
      other origins, such as sedimentary ooids or volcanic accretionary lapilli, often
      with just a hand lens. However, petrographic identification becomes progressively
      more difficult as the spherules become smaller or more altered. Moreover, impact
      spherules in other layers of other ages sometimes have different textures, so the
      ones described here are not representative of all types of impact spherules. They
      are provided as a starting point for researchers interested in identifying impact
      spherule layers. Given the visible record of impacts on the Moon and the much
      greater mass of the Earth, there should be many more impact spherule layers on
      Earth than have been discovered to date.

PMID- 12804365
TI  - Impact at the Permo-Triassic boundary: a critical evaluation.
AB  - The recognition in 1980 of a signature of an extraterrestrial impact at the
      Cretaceous-Tertiary boundary and its apparent involvement with the mass
      extinction generated considerable enthusiasm for impacts at other mass
      extinctions. Numerous claims of impact evidence for the Permo-Triassic mass
      extinction (251.6 Ma), the largest of the Phanerozoic mass extinctions, have
      generally been rejected, found wanting, or been difficult to reproduce. Despite
      this lack of repeatable support, considerable available evidence is consistent
      with an impact, including the rapidity of extinction, coincident carbon shift,
      and evident correlation between terrestrial and marine extinctions. However
      attractive the hypothesis, the coincidence with the Siberian flood basalts and
      the complex nature of the carbon shift are in conflict with an impact. The most
      intriguing possibility is that the greatest mass extinction of the Phanerozoic
      left signals very similar to the end-Cretaceous mass extinction but was produced
      by entirely Earth-bound processes. If true, this would tell us far more about the
      nature of ecosystems and how they fail than would identification of another
      impact.

PMID- 12804366
TI  - Fullerenes and interplanetary dust at the Permian-Triassic boundary.
AB  - We recently presented new evidence that an impact occurred approximately 250
      million years ago at the Permian-Triassic boundary (PTB), triggering the most
      severe mass extinction in the history of life on Earth. We used a new
      extraterrestrial tracer, fullerene, a third carbon carrier of noble gases besides
      diamond and graphite. By exploiting the unique properties of this molecule to
      trap noble gases inside of its caged structure (helium, neon, argon), the origin
      of the fullerenes can be determined. Here, we present new evidence for fullerenes
      with extraterrestrial noble gases in the PTB at Graphite Peak, Antarctica,
      similar to PTB fullerenes from Meishan, China and Sasayama, Japan. In addition,
      we isolated a (3)He-rich magnetic carrier phase in three fractions from the
      Graphite Peak section. The noble gases in this magnetic fraction were similar to
      zero-age deep-sea interplanetary dust particles (IDPs) and some magnetic grains
      isolated from the Cretaceous-Tertiary boundary. The helium and neon isotopic
      compositions for both the bulk Graphite Peak sediments and an isolated magnetic
      fraction from the bulk material are consistent with solar-type gases measured in
      zero-age deep-sea sediments and point to a common source, namely, the flux of
      IDPs to the Earth's surface. In this instance, the IDP noble gas signature for
      the bulk sediment can be uniquely decoupled from fullerene, demonstrating that
      two separate tracers are present (direct flux of IDPs for (3)He vs. giant impact
      for fullerene).

PMID- 12804367
TI  - A search for soot from global wildfires in central Pacific Cretaceous-Tertiary
      boundary and other extinction and impact horizon sediments.
AB  - Hypotheses of global wildfires following the Cretaceous-Tertiary (KT) boundary
      impact are supported by high concentrations of elemental carbon (3.6 mg cm(-2))
      and soot (1.8 mg cm(-2)) in DSDP Site 465, which was located several thousand
      kilometers from potential continental sources at 65 Ma. Soot is not preserved at
      four other central Pacific KT localities, but this is attributed to loss during
      oxic diagenesis. We find no evidence for wildfires related to major impacts in
      the late Eocene or to Ir anomalies and extinctions in the late Cenomanian.

PMID- 12804368
TI  - Chicxulub and climate: radiative perturbations of impact-produced S-bearing
      gases.
AB  - We use one-dimensional (1D) atmospheric models coupled to a sulfate aerosol model
      to investigate climate forcing and short-term response to stratospheric sulfate
      aerosols produced by the reaction of S-bearing gases and water vapor released in
      the Chicxulub impact event. A 1D radiation model is used to assess the climate
      forcing due to the impact-related loading of S-bearing gases. The model suggests
      that a climate forcing 100 times larger than that from the Pinatubo volcanic
      eruption is associated with the Chicxulub impact event for at least 2 years after
      the impact. In particular, we find a saturation effect in the forcing, that is,
      there is no significant difference in the maximum forcing between the highest
      (approximately 300 Gt) and lowest (approximately 30 Gt) estimated stratospheric S
      loading from the Chicxulub impact. However, higher S-loads increase the overall
      duration of the forcing by several months. We use a single column model for a
      preliminary investigation of the short-term climate response to the impact
      related production of sulfate aerosols (the lack of horizontal feedbacks limits
      the usefulness of the single column model to the first few days after the
      impact). Compared with the present steady-state climate, the introduction of
      large amounts of sulfate aerosols in the stratosphere results in a significant
      cooling of the Earth's surface. A long-term climate response can only be
      investigated with the use of a three-dimensional atmospheric model, which allows
      for the atmospheric circulation to adjust to the perturbation. Overall, although
      the climate perturbation to the forcing appears to be relatively large, the
      geologic record shows no sign of a significant long-term climatic shift across
      the K/T boundary, which is indicative of a fast post-impact climatic recovery.

PMID- 12804369
TI  - Cenozoic bolide impacts and biotic change in North American mammals.
AB  - North American mammals experienced a major mass extinction at the
      Cretaceous/Tertiary (K/T) boundary that is tied unambiguously to the Chicxulub
      impact event. Immediately afterwards, there was an immense adaptive radiation
      that greatly expanded taxonomic diversity and the range of body sizes and
      ecological strategies. However, ties between later, Cenozoic impact events and
      specific episodes in mammalian evolution cannot be demonstrated. A time series of
      maximum known crater sizes within 1.0-million-year-long temporal bins is shown
      not to cross-correlate with five separate measures of taxonomic turnover rate,
      one measure of change in relative taxonomic composition, and four measures of
      change in body mass distributions. The lack of correlation persists even after
      excluding the volatile Paleocene mammalian data, adding dummy data to represent
      intervals without known craters, or lagging the time series against each other
      for up to 5 million years. Furthermore, the data fail to support broad-brush
      correspondences between ages of major (>20 km in diameter) craters and the timing
      of five key, post-K/T biotic transitions, including medium-sized extinction
      episodes during the late Paleocene and latest Miocene. The results challenge the
      idea that extraterrestrial impacts drive all, most, or even many extinction and
      radiation episodes in terrestrial organisms, and add to other evidence that
      natural, long-term biotic changes are often independent of changes in the
      physical environment.

PMID- 12804370
TI  - Comparing the evidence relevant to impact and flood basalt at times of major mass
      extinctions.
AB  - The five major mass extinctions identified in 1982 by Raup and Sepkoski have
      expanded to six, with the suggestion that the Permian-Triassic extinction was a
      double event. Is there a general explanation for great mass extinctions, or can
      they result from different triggers, or even from internal system instabilities?
      The two most-discussed candidates for a general extinction mechanism are impacts
      and flood-basalt eruptions. A compilation of evidence for impact at the times of
      mass extinctions shows that this cause is abundantly confirmed in the case of the
      Cretaceous-Tertiary extinction and the late Eocene, which is a time of minor and
      gradual extinction, but little or no evidence connects other major extinctions to
      impact. On the other hand, there is a remarkable time correlation between flood
      basalts and four major extinctions, but no other evidence that flood basalts
      cause mass extinctions. The evidence for an impact-extinction linkage is
      strikingly different from that for a connection between flood basalts and
      extinctions. Flood basalts cover larger areas than craters and their associated
      thick ejecta blankets, which are thus less likely to be found. Impacts distribute
      proxies globally at instantaneous time horizons, whereas flood-basalt events are
      extended in time, and no remote proxies have been recognized. Many global killing
      mechanisms have been proposed in the case of impacts, but few have been suggested
      for flood basalts. It is possible that flood basalts are triggered by impact, but
      it is not obvious how impacts could result from anything other than chance. The
      hypothesis that impacts are the general cause of mass extinctions has not
      received supporting evidence, but has not been falsified. The hypothesis that
      flood basalts are the general cause of mass extinctions is supported by evidence
      from timing, but is not susceptible to falsification. Other candidates for
      general extinction causes, especially sea-level changes and system instabilities,
      would require separate treatment. The question is still very much open.

PMID- 12804371
TI  - The impact crater as a habitat: effects of impact processing of target materials.
AB  - Impact structures are a rare habitat on Earth. However, where they do occur they
      can potentially have an important influence on the local ecology. Some of the
      types of habitat created in the immediate post-impact environment are not
      specific to the impact phenomenon, such as hydrothermal systems and crater lakes
      that can be found, for instance, in post-volcanic environments, albeit with
      different thermal characteristics than those associated with impact. However,
      some of the habitats created are specifically linked to processes of impact
      processing. Two examples of how impact processing of target materials has created
      novel habitats that improve the opportunities for colonization are found in the
      Haughton impact structure in the Canadian High Arctic. Impact-shocked rocks have
      become a habitat for endolithic microorganisms, and large, impact-shattered
      blocks of rock are used as resting sites by avifauna. However, some materials
      produced by an impact, such as melt sheet rocks, can make craters more
      biologically depauperate than the area surrounding them. Although there are no
      recent craters with which to study immediate post-impact colonization, these data
      yield insights into generalized mechanisms of how impact processing can influence
      post-impact succession. Because impact events are one of a number of processes
      that can bring localized destruction to ecosystems, understanding the manner in
      which impact structures are recolonized is of ecological interest. Impact craters
      are a universal phenomenon on solid planetary surfaces, and so they are of
      potential biological relevance on other planetary surfaces, particularly Mars.

PMID- 12804372
TI  - Impacts and evolution: future prospects.
AB  - The discipline of astrobiology includes the dynamics of biological evolution. One
      of the major ways that the cosmos influences life is through the catastrophic
      environmental disruptions caused when comets and asteroids collide with a planet.
      We now recognize that such impacts have caused mass extinctions and played a
      major role in determining the evolution of life on Earth. The time-averaged
      impact flux as a function of projectile energy can be derived from lunar
      cratering statistics as well as the current population of near Earth asteroids
      (NEAs). Effects of impacts of various energies can be modeled, using data from
      historic impacts [such as the Cretaceous-Tertiary (KT) impactor 65 million years
      ago] and the observed 1994 bombardment of Jupiter by fragments of Comet Shoemaker
      Levy 9. It is of particular interest to find from such models that the
      terrestrial environment is highly vulnerable to perturbation from impacts, so
      that even such a small event as the KT impact (by a projectile 10-15 km in
      diameter) can lead to a mass extinction. Similar considerations allow us to model
      the effects of still smaller (and much more likely) impacts, down to the size of
      the asteroid that exploded over Tunguska in 1908 (energy approximately 10
      megatons). Combining the impact flux with estimates of environmental and
      ecological effects reveals that the greatest contemporary hazard is associated
      with impactors near 1 million megatons in energy (approximately 2 km in diameter
      for an asteroid). The current impact hazard is significant relative to other
      natural hazards, and arguments can be developed to illuminate a variety of public
      policy issues. The first priority in any plan for defense against impactors is to
      survey the population of Earth-crossing NEAs and project their orbits forward in
      time. This is the purpose of the Spaceguard Survey, which has already found more
      than half of the NEAs >1 km in diameter. If there is an NEA on a collision course
      with Earth, it can be discovered and the impact predicted with decades or more of
      warning. It is then possible to consider how to deflect or disrupt the NEA.
      Unlike other natural hazards, the impact risk can be largely eliminated, given
      sufficient advanced knowledge to take action against the threatening projectile.

PMID- 12804373
TI  - Exchange of meteorites (and life?) between stellar systems.
AB  - It is now generally accepted that meteorite-size fragments of rock can be ejected
      from planetary bodies. Numerical studies of the orbital evolution of such
      planetary ejecta are consistent with the observed cosmic ray exposure times and
      infall rates of these meteorites. All of these numerical studies agree that a
      substantial fraction (up to one-third) of the ejecta from any planet in our Solar
      System is eventually thrown out of the Solar System during encounters with the
      giant planets Jupiter and Saturn. In this paper I examine the probability that
      such interstellar meteorites might be captured into a distant solar system and
      fall onto a terrestrial planet in that system within a given interval of time.
      The overall conclusion is that it is very unlikely that even a single meteorite
      originating on a terrestrial planet in our solar system has fallen onto a
      terrestrial planet in another stellar system, over the entire period of our Solar
      System's existence. Although viable microorganisms may be readily exchanged
      between planets in our solar system through the interplanetary transfer of
      meteoritic material, it seems that the origin of life on Earth must be sought
      within the confines of the Solar System, not abroad in the galaxy.

PMID- 12804375
TI  - Serologic survey of domestic animals for zoonotic arbovirus infections in the
      Lacandon Forest region of Chiapas, Mexico.
AB  - A serologic survey in domestic animals (birds and mammals) was conducted in four
      communities located in the Lacandon Forest region of northeastern Chiapas,
      Mexico, during June 29 to July 1, 2001, with the objective to identify zoonotic
      arboviruses circulating in this area. We collected 202 serum samples from healthy
      domestic chickens, geese, ducks, turkeys, horses and cattle. The samples were
      tested by plaque-reduction neutralization test for antibodies to selected
      mosquito-borne flaviviruses (family Flaviviridae), including St. Louis
      encephalitis (SLE), Rocio (ROC), Ilheus (ILH), Bussuquara (BSQ), and West Nile
      (WN) viruses, and selected alphaviruses (family Togaviridae), including Western
      equine encephalitis (WEE), Eastern equine encephalomyelitis (EEE), and Venezuelan
      equine encephalitis (VEE) viruses. Neutralizing antibodies to SLE virus were
      detected in two (8%) of 26 turkeys, 15 (23%) of 66 cattle, and three (60%) of
      five horses. Antibodies to VEE virus were detected in 29 (45%) of 65 cattle.
      Because some of these animals were as young as 2 months old, we demonstrated
      recent activity of these two viruses. Sub-typing of the VEE antibody responses
      indicated that the etiologic agents of these infections belonged to the IE
      variety of VEE, which has been reported from other regions of Chiapas. WN virus
      neutralizing antibodies were detected in a single cattle specimen (PRNT(90) =
      1:80) that also circulated SLE virus-neutralizing antibodies (PRNT(90) = 1:20),
      suggesting that WN virus may have been introduced into the region. We also
      detected weak neutralizing activity to BSQ virus in four cattle and a chicken
      specimen, suggesting the presence of this or a closely related virus in Mexico.
      There was no evidence for transmission of the other viruses (ROC, ILH, EEE, WEE)
      in the study area.

PMID- 12804376
TI  - Natural history of Q fever in goats.
AB  - During the spring of 1999, an outbreak of Q fever resulted in 30 abortions among
      174 (17%) goats in a caprine cooperative in Newfoundland. The intent of this
      study was to determine the natural history of Coxiella burnetii infection in
      goats. Twenty-four goats on one farm were followed through the next two kidding
      seasons following the Q fever outbreak. Antibodies to phases I and II C. burnetii
      were determined using an indirect immunofluorescence assay and samples of
      placentas were cultured for C. burnetii and polymerase chain reaction was used to
      identify C. burnetii DNA. Phase I antibody was present in high levels and was
      maintained over the study period, while phase II antibody levels declined to the
      seronegative range in 60% of the infected goats. Molecular studies suggest that
      excretion of C. burnetii in the placenta of infected goats seems to be limited to
      the next kidding season following an outbreak. We therefore conclude that C.
      burnetii infection in goats seems to be limited to two kidding seasons. Phase I
      antibody levels are maintained, while phase II antibody levels decline.

PMID- 12804377
TI  - Identification of Ehrlichia chaffeensis, Anaplasma phagocytophilum, and A. bovis
      in Haemaphysalis longicornis and Ixodes persulcatus ticks from Korea.
AB  - A total of 1,467 tick (1,463 of Haemaphysalis longicornis, three of Ixodes
      persulcatus and one of I. turdus) collected from nine provinces of Korea were
      examined by TaqMan real-time PCR for the presence of Ehrlichia and Anaplasma
      species. One set of primers and a probe were designed for detection of all of the
      Ehrlichia and Anaplasma species. Template DNAs (total 803) were prepared either
      from pools of larvae, nymphs, adult males and females, or from the salivary gland
      and midgut of adult ticks. Only DNAs positive in TaqMan PCR were examined for A.
      phagocytophilum with nested PCR and for E. chaffeensis with PCR. Four A.
      phagocytophilum 16S rRNA gene PCR products were sequenced for comparison with
      sequences previously reported. Amplification of a 16S rRNA gene fragment of
      Ehrlichia and Anaplasma species was observed in 364 tick DNAs (45.3% of the
      total). Of these 364 positive ticks, species-specific PCRs confirmed that 35 H.
      longicornis and one I. persulcatus were positive for A. phagocytophilum and one
      I. persulcatus was positive in E. chaffeensis. Except for one (AB-GGHL, GenBank
      accession number [GAN] AF470698), three of the four 16S rRNA gene fragment
      sequences of the A. phagocytophilum-positive samples were similar or identical to
      the sequences of variants of A. phagocytophilum deposited in GenBank. The 16S
      rRNA gene fragment sequence of AB-GGHL was similar to that of Anaplasma
      (Ehrlichia) bovis 16S rRNA (GAN U03775). The identities of the Anaplasmataceae
      genus and species DNA in the 327 ticks that could not be confirmed infected with
      either E. chaffeensis, A. phagocytophilum, or A. bovis are not known. This study
      is the first to demonstrate the presence of E. chaffeensis, A. phagocytophilum
      and A. bovis in Korean ticks.

PMID- 12804378
TI  - Migratory birds modeled as critical transport agents for West Nile Virus in North
      America.
AB  - West Nile Virus has spread more rapidly than expected in the Western Hemisphere.
      We tested Culex mosquitoes and long-distance migratory birds as potential agents
      of spread for the virus, using a series of techniques, as follows. (1) Mosquito
      vector distributions were modeled using an ecological niche modeling approach
      (GARP) to produce a map of suitability of the landscape for mosquito transmission
      of the virus. (2) Simulations of spread were developed with an algorithm
      originally developed for modeling the spread of wildfires (EMBYR), seeding an
      initial presence of the virus in the New York City area. (3) Alternative spread
      scenarios were developed as (a) just mosquitoes as movement agents (spread
      simulation seeded once at New York City and allowed to spread across the mosquito
      suitability surface), versus (b) spread via mosquitoes on local scales in tandem
      with long-distance colonization with migratory birds as movement agents (spread
      simulation seeded once at New York City, and again at sites sampled from the
      winter destinations of birds breeding in southeastern New York State). The first
      scenario (mosquitoes only) did not coincide with observed patterns of spread,
      whereas the second (mosquitoes and migratory birds) coincided closely, suggesting
      that observed patterns of spread are best explained with migratory birds as
      critical long-distance transport agents; the virus, in regions to which it is
      transported by migratory birds, then is transmitted enzootically via mosquitoes.
      Similar simulations of spread were used to predict extensions of the virus in the
      Western Hemisphere in coming years.

PMID- 12804379
TI  - Ixodes sinensis: competence as a vector to transmit the Lyme disease spirochete
      Borrelia garinii.
AB  - In order to determine the principal vectors of Lyme disease in South China, the
      capability of Ixodes sinensis to transmit Lyme disease spirochetes transstadially
      was estimated in the laboratory. Results suggest that I. sinensis can acquire
      active Lyme disease spirochetes by feeding on infected mice of Kunming strains
      (KM), and the positive rates of larvae and nymph I. sinensis infected were 94.0%
      and 92.0%, respectively. I. sinensis maintained active spirochetes during blood
      digestion and molting periods; the subsequent questing tick stages were also
      found to be infected and infectious to naive KM mice, which resulted in more than
      66.7% spirochete-positive KM mice. I. sinensis can transmit the Lyme disease
      spirochete Borrelia garinii from infected KM mice to naive KM mice during larvae
      nymph and nymph-adult periods. Therefore, I. sinensis might be considered as a
      competent vector of Lyme disease in South China.

PMID- 12804380
TI  - Babesiosis diagnosis and treatment.
AB  - Human babesiosis due to Babesia microti is an emerging malaria-like infection
      that is endemic in parts of the northeastern and northcentral United States. The
      clinical manifestations of babesiosis range from subclinical illness to fulminant
      disease resulting in death. Prompt and accurate diagnosis is difficult because
      the signs and symptoms are non-specific. A CBC is a useful screening test since
      anemia and thrombocytopenia are commonly observed and parasites may be visualized
      on blood smear. Conclusive diagnosis of this disease generally depends upon
      microscopic examination of thin blood smears. Babesia frequently are overlooked,
      however, because parasitemia tends to be sparse, often infecting fewer than 1% of
      erythrocytes early in the course of the illness. Identification of amplifiable
      babesial DNA by polymerase chain reaction (PCR) has comparable sensitivity and
      specificity to microscopic analysis of thin blood smear for detection of babesia
      in blood. Serologic testing provides useful supplementary evidence of infection
      because a robust antibody response characterizes human babesial infection, even
      at the time that parasitemia first becomes detectable. The currently recommended
      therapy for babesiosis is a 7-10-day course of clindamycin (600 mg every 6 h) and
      quinine (650 mg every 8 h). Recently, azithromycin (500-600 mg on day 1, and 250
      600 mg on subsequent days) and atovaquone (750 mg every 12 h) was found to be
      equally effective in treating adults experiencing babesiosis. This combination
      also was associated with fewer adverse reactions than clindamycin and quinine.
      Exchange transfusion is a potentially life-saving therapy for patients suffering
      from severe disease with high parasitemia (>5%), significant hemolysis, or renal
      or pulmonary compromise. Babesiosis may be prevented by avoiding areas such as
      tall grass and brush where ticks, deer, and mice are known to thrive.

PMID- 12804381
TI  - A career path in arbovirology--an interview with Robert E. Shope, M.D.

PMID- 12804382
TI  - Amodiaquine for treating malaria.
AB  - BACKGROUND: Amodiaquine has been widely used to treat malaria. Fatal adverse
      reactions have been reported in adults taking it for prophylaxis. This has led
      some authorities to suggest it is withdrawn as a first line treatment for
      malaria. OBJECTIVES: To compare amodiaquine with chloroquine or sulfadoxine
      pyrimethamine for treating uncomplicated Plasmodium falciparum malaria. SEARCH
      STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials
      register (February 2003), The Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1980 to
      December 2002), LILACS (February 2003). We contacted researchers in the field and
      pharmaceutical companies. SELECTION CRITERIA: Randomised and quasi-randomised
      trials. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data
      and assessed trial quality. MAIN RESULTS: 56 studies included, mostly from
      Africa. Treatment allocation was adequately concealed in three trials, and
      unclear or inadequate in the remainder. Amodiaquine was more effective than
      chloroquine for parasite clearance (day 7, Peto odds ratio 4.42 (95% confidence
      interval 3.65 to 5.35); day 14, Peto odds ratio 6.44 (95% confidence interval
      (CI) 5.09 to 8.15). Comparisons with sulfadoxine/pyrimethamine were more mixed,
      with sulfadoxine/pyrimethamine more effective on day 28 (Peto odds ratio 0.41;
      95% CI 0.28 to 0.61). No significant difference for adverse events was observed
      between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported
      adverse effects were minor or moderate. No life threatening events were detected.
      REVIEWER'S CONCLUSIONS: There is evidence to support the continued use of
      amodiaquine to treat uncomplicated malaria, although local drug resistance
      patterns need to be considered. Monitoring for adverse events should continue.

PMID- 12804383
TI  - Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia is a relatively common complication of pregnancy.
      Eclampsia, the occurrence of one or more convulsions (fits) in association with
      the syndrome of pre-eclampsia, is a rare but serious complication.
      Anticonvulsants are used in the belief they help prevent eclamptic fits and so
      improve outcome. OBJECTIVES: The objective was to assess the effects of
      anticonvulsants for pre-eclampsia on the women and their children. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (28 November 2002), and the Cochrane Controlled Trials Register (The Cochrane
      Library, Issue 3, 2002). SELECTION CRITERIA: Randomised trials comparing
      anticonvulsants with placebo or no anticonvulsants or comparisons of different
      anticonvulsants in women with pre-eclampsia. DATA COLLECTION AND ANALYSIS: Two
      reviewers assessed trial quality and extracted data independently. MAIN RESULTS:
      Six trials (11,444 women) compared magnesium sulphate with placebo or no
      anticonvulsant. There was more than a halving in the risk of eclampsia associated
      with magnesium sulphate (relative risk (RR) 0.41, 95% confidence interval (CI)
      0.29 to 0.58; number needed to treat (NNT) 100, 95% CI 50 to 100). The risk of
      dying was non-significantly reduced by 46% for women allocated magnesium sulphate
      (RR 0.54, 95% CI 0.26 to 1.10). For serious maternal morbidity RR 1.08, 95% CI
      0.89 to 1.32. Side effects were more common with magnesium sulphate (24% versus
      5%; RR 5.26, 95% CI 4.59 to 6.03; NNT for harm 6, 95% CI 6 to 5). The main side
      effect was flushing. Risk of placental abruption was reduced for women allocated
      magnesium sulphate (RR 0.64, 95% CI 0.50 to 0.83; NNT 100, 95% CI 50 to 1000).
      Women allocated magnesium sulphate had a small increase (5%) in the risk of
      caesarean section (95% CI 1% to 10%). There was no overall difference in the risk
      of stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Magnesium
      sulphate was better than phenytoin for reducing the risk of eclampsia (two trials
      2241 women; RR 0.05, 95% CI 0.00 to 0.84), but with an increased risk of
      caesarean section (RR 1.21, 95% CI 1.05 to 1.41). It was also better than
      nimodipine (1 trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77). REVIEWER'S
      CONCLUSIONS: Magnesium sulphate more than halves the risk of eclampsia, and
      probably reduces the risk of maternal death. It does not improve outcome for the
      baby, in the short term. A quarter of women have side effects, particularly
      flushing.

PMID- 12804384
TI  - Antiplatelet therapy for acute ischaemic stroke.
AB  - BACKGROUND: In patients with acute ischaemic stroke, platelets become activated.
      Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and
      reduce the risk of early recurrent ischaemic stroke. This might reduce the risk
      of early death and improve long-term outcome in survivors. However, antiplatelet
      therapy might also increase the risk of fatal or disabling intracranial
      haemorrhage. OBJECTIVES: The aim of this review is to assess the efficacy and
      safety of antiplatelet therapy in acute ischaemic stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched August 2002),
      the Cochrane Controlled Trials Register (CCTR) (Cochrane Library Issue 1 2002),
      MEDLINE (June 1998-October 2001), and EMBASE (June 1998-February 2002). In 1998,
      for previous versions of this review, we searched the register of the
      Antiplatelet Trialists Collaboration, MedStrategy and contacted relevant drug
      companies. SELECTION CRITERIA: Randomised trials comparing antiplatelet therapy
      (started within 14 days of the stroke) with control in patients with definite or
      presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently applied the inclusion criteria and assessed trial quality, and for
      the included trials, extracted and cross-checked the data. MAIN RESULTS: Nine
      trials involving 41,399 patients were included. Two trials testing aspirin 160 to
      300 mg once daily started within 48 hours of onset contributed 98% of the data.
      The maximum follow-up was six months. With treatment, there was a significant
      decrease in death or dependency at the end of follow-up (OR = 0.94; 95% CI 0.91
      to 0.98). In absolute terms, 13 more patients were alive and independent at the
      end of follow-up for every 1000 patients treated. Furthermore, treatment
      increased the odds of making a complete recovery from the stroke (OR = 1.06; 95%
      CI 1.01 to 1.11). In absolute terms, 10 more patients made a complete recovery
      for every 1000 patients treated. Antiplatelet therapy was associated with a small
      but definite excess of 2 symptomatic intracranial haemorrhages for every 1000
      patients treated, but this was more than offset by a reduction of 7 recurrent
      ischaemic strokes and about one pulmonary embolus for every 1000 patients
      treated. REVIEWER'S CONCLUSIONS: Antiplatelet therapy with aspirin 160 to 300 mg
      daily, given orally (or per rectum in patients who cannot swallow), and started
      within 48 hours of onset of presumed ischaemic stroke reduces the risk of early
      recurrent ischaemic stroke without a major risk of early haemorrhagic
      complications and improves long-term outcome.

PMID- 12804385
TI  - Antidepressants for smoking cessation.
AB  - BACKGROUND: There at least two reasons to believe antidepressants might help in
      smoking cessation. Depression may be a symptom of nicotine withdrawal, and
      smoking cessation sometimes precipitates depression. In some individuals,
      nicotine may have antidepressant effects that maintain smoking. Antidepressants
      may substitute for this effect. OBJECTIVES: The aim of this review is to assess
      the effect of antidepressant medications in aiding long-term smoking cessation.
      The drugs include bupropion; doxepin; fluoxetine; imipramine; moclobemide;
      nortriptyline; paroxetine; selegiline; sertraline, tryptophan and venlafaxine.
      SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register
      which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and
      other reviews and meeting abstracts, in December 2002. SELECTION CRITERIA: We
      considered randomized trials comparing antidepressant drugs to placebo or an
      alternative therapeutic control for smoking cessation. For the meta-analysis, we
      excluded trials with less than six months follow-up. DATA COLLECTION AND
      ANALYSIS: We extracted data in duplicate on the type of study population, the
      nature of the drug therapy, the outcome measures, method of randomization, and
      completeness of follow-up. The main outcome measure was abstinence from smoking
      after at least six months follow-up in patients smoking at baseline, expressed as
      an odds ratio (OR). We used the most rigorous definition of abstinence for each
      trial, and biochemically validated rates if available. Where appropriate, we
      performed meta-analysis using a fixed effects model. MAIN RESULTS: There was one
      trial each of moclobemide, sertraline and venlafaxine, two of fluoxetine, five of
      nortriptyline, and twenty trials of bupropion. In the bupropion trials, 18 had a
      placebo arm, two of which tested long-term use to prevent relapse. Nine of the
      bupropion trials have been published in full. Nortriptyline (five trials, OR
      2.80, 95% CI 1.81 - 4.32) and bupropion (16 trials, OR 1.97, 95% CI 1.67 - 2.34)
      both increased the odds of cessation. In one trial the combination of bupropion
      and nicotine patch produced slightly higher quit rates than patch alone, but this
      was not replicated in a second study. Two trials of extended therapy with
      bupropion to prevent relapse after initial cessation have failed to detect a long
      term benefit. REVIEWER'S CONCLUSIONS: The antidepressants bupropion and
      nortriptyline can aid smoking cessation but selective serotonin reuptake
      inhibitors (e.g. fluoxetine) do not.

PMID- 12804386
TI  - Biochemical tests of placental function for assessment in pregnancy.
AB  - BACKGROUND: Biochemical tests of placental or feto-placental function were widely
      used in the 1960s and 1970s in high-risk pregnancies to try to predict, and thus
      try to avoid, adverse fetal outcome. OBJECTIVES: To assess the effects of
      performing biochemical tests of placental function in high-risk, low-risk, or
      unselected pregnancies. SEARCH STRATEGY: Comprehensive electronic search of the
      Cochrane Pregnancy and Childbirth Group trials register (February 2003).
      SELECTION CRITERIA: Controlled trials (randomized or 'quasi-randomized') that
      compare the use of biochemical tests of placental function in pregnancy with non
      use. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were
      extracted by the reviewer. MAIN RESULTS: A single eligible trial of poor quality
      was identified. It involved 622 women with high-risk pregnancies who had had
      plasma (o)estriol estimations. Women were allocated to have their (o)estriol
      results revealed or concealed on the basis of hospital record number (with
      attendant risk of selection bias). There were no obvious differences in perinatal
      mortality (relative risk (RR) 0.88, 95% confidence interval (CI) 0.36 to 2.13) or
      planned delivery (RR 0.97, 95% CI 0.81 to 1.15) between the two groups.
      REVIEWER'S CONCLUSIONS: The available trial data do not support the use of
      (o)estriol estimation in high-risk pregnancies. The single small trial available
      does not have the power to exclude a beneficial effect but this is probably of
      historical interest since biochemical testing has been superseded by biophysical
      testing in antepartum fetal assessment.

PMID- 12804387
TI  - Fetal electrocardiogram (ECG) for fetal monitoring during labour.
AB  - BACKGROUND: Animal and human studies have shown that fetal hypoxaemia during
      labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably
      (1) the relation of the PR to RR intervals and (2) elevation or depression of the
      ST segment. Technical systems have therefore been developed to monitor the fetal
      ECG during labour as an adjunct to continuous electronic fetal heart rate
      monitoring with the aim of improving fetal outcome and minimising unnecessary
      obstetric interference. OBJECTIVES: To compare the effects of analysis of fetal
      ECG waveforms during labour with alternative methods of fetal monitoring. SEARCH
      STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was
      searched (September 2002). SELECTION CRITERIA: Randomised trials comparing fetal
      ECG waveform analysis with alternative methods of fetal monitoring during labour.
      DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were
      performed by the reviewer, without blinding. MAIN RESULTS: Three trials including
      a total of 8357 pregnant women were included. The trials were of sound
      methodological quality. All three trials assessed the use of the fetal ECG as an
      adjunct to continuous electronic fetal heart rate monitoring during labour. One
      study assessed PR intervals; two assessed the ST segment. The use of ST waveform
      analysis (7400 women) was associated with fewer babies with severe metabolic
      acidosis at birth (cord pH less than 7.05 and base deficit greater than 12
      mmol/L) (relative risk (RR) 0.44, 95% confidence interval (CI) 0.26 to 0.75, data
      from 6672 babies). This was achieved along with fewer fetal scalp samples during
      labour (RR 0.86, 95% CI 0.76 to 0.98) and fewer operative deliveries (RR 0.89,
      95% CI 0.82 to 0.97). Apart from a trend (that did not achieve statistical
      significance) towards fewer operative deliveries (RR 0.87, 95% CI 0.76 to 1.01),
      there was little evidence that monitoring by PR interval analysis conveyed any
      benefit. This may reflect limitations of the technique or, alternatively, the
      smaller numbers available for analysis from the single trial (957 women).
      REVIEWER'S CONCLUSIONS: These findings support the use of fetal ST waveform
      analysis when a decision has been made to undertake continuous electronic fetal
      heart rate monitoring during labour. However, in most labours, technically
      satisfactory cardiotocographic traces can be obtained by external ultrasound
      monitors which are less invasive than internal scalp electrodes (which are
      required for electrocardiographic (ECG) analysis). A better approach might be to
      restrict fetal ST waveform analysis to those fetuses demonstrating disquieting
      features on cardiotocography.

PMID- 12804388
TI  - Nasal continuous positive airways pressure immediately after extubation for
      preventing morbidity in preterm infants.
AB  - BACKGROUND: Preterm infants being extubated following a period of intermittent
      positive pressure ventilation via an endotracheal tube are at risk of developing
      respiratory failure as a result of apnea, respiratory acidosis and hypoxia. Nasal
      continuous positive airway pressure appears to stabilise the upper airway,
      improve lung function and reduce apnea and may therefore have a role in
      facilitating extubation in this population. OBJECTIVES: In preterm infants having
      their endotracheal tube removed following a period of intermittent positive
      pressure ventilation (IPPV), does management with nasal continuous positive
      airways pressure (NCPAP) lead to an increased proportion remaining free of
      additional ventilatory support, compared to extubation directly to headbox
      oxygen? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal
      Trials, MEDLINE up to November 2002, Cochrane Controlled Trials Register (The
      Cochrane Library, Issue 4, 2002), previous reviews including cross references,
      abstracts of conferences and symposia proceedings, expert informants and journal
      handsearching mainly in the English language. SELECTION CRITERIA: All trials
      utilising random or quasi-random patient allocation, in which NCPAP (delivered by
      any method) was compared with headbox oxygen for post-extubation care were
      included. Methodological quality was assessed independently by the two authors.
      DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two
      authors. Prespecified subgroup analysis to determine the impact of different
      levels of NCPAP, differences in duration of IPPV and use of aminophylline were
      also performed using the same package. Data were analysed using relative risk
      (RR), risk difference (RD) and number needed to treat (NNT). MAIN RESULTS: Nasal
      CPAP, when applied to preterm infants being extubated following IPPV, reduces the
      incidence of adverse clinical events (apnea, respiratory acidosis and increased
      oxygen requirements) indicating the need for additional ventilatory support [RR
      0.62 (0.49, 0.77), RD -0.17 (-0.24,-0.10), NNT 6 (4,10)]. REVIEWER'S CONCLUSIONS:
      IMPLICATIONS FOR PRACTICE: nasal CPAP is effective in preventing failure of
      extubation in preterm infants following a period of endotracheal intubation and
      IPPV. Implication for research: further definition of the gestational age and
      weight groups in whom these results apply is required. Optimal levels of NCPAP as
      well as methods of administration remain to be determined.

PMID- 12804389
TI  - Benzodiazepines for neuroleptic-induced tardive dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement
      disorder of the orofacial region often caused by the use of neuroleptic drugs. A
      wide range of strategies have been used to help manage tardive dyskinesia and,
      for those who are unable to have their antipsychotic medication stopped or
      substantially changed, the benzodiazepine group of drugs has been suggested as a
      useful adjunctive treatment. OBJECTIVES: To determine the effects of
      benzodiazepines for people with neuroleptic-induced tardive dyskinesia and
      schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic
      searches of Biological Abstracts (1982-2002), the Cochrane Schizophrenia Group's
      Register of trials (February 2002), EMBASE (1980-2002), LILACS (1982-2002),
      MEDLINE (1966-2002), PsycLIT (1974-2002), SCISEARCH (2002), hand searching the
      references of all identified studies and contacting the first author of each
      included trial. SELECTION CRITERIA: All randomised clinical studies focusing on
      people with both schizophrenia or other chronic mental illnesses and neuroleptic
      induced tardive dyskinesia and comparing benzodiazepines with placebo or no
      intervention. DATA COLLECTION AND ANALYSIS: Studies were reliably selected,
      quality assessed and data extracted. Data were excluded where more than 50% of
      participants in any group were lost to follow up. For binary outcomes a fixed
      effects risk ratio (RR) and its 95% confidence interval (CI) was calculated.
      Where possible, the weighted number needed to treat/harm statistic (NNT/H), and
      its 95% confidence interval (CI), was also calculated. For continuous outcomes,
      endpoint data were preferred to change data. Non-skewed data from valid scales
      were synthesised using a weighted mean difference (WMD). If statistical
      heterogeneity was found by Mantel-Haenszel chi-square test, random effects models
      were used. MAIN RESULTS: Two small trials (total n=32) were included. Using
      benzodiazepines as adjunctive treatment did not result in any clear changes for a
      series of tardive dyskinesia medium term outcomes (RR not improved to a
      clinically important extent 1.08 CI 0.57 to 2.05, n=30, 2 RCTs; RR not improved
      at all 1.19 CI 0.3 to 5.3, n=30, 2 RCTs; RR deterioration 1.85 CI 0.3 to 10.1,
      n=30, 2 RCTs). Adverse effects were not reported. REVIEWER'S CONCLUSIONS: The
      2002 update has added almost no extra data. This is clearly not an area of active
      research. Benzodiazepines may have something to contribute to the care of people
      with tardive dyskinesia but the use of this group of compounds should be
      considered experimental. Large definitive studies are indicated.

PMID- 12804390
TI  - Miscellaneous treatments for neuroleptic-induced tardive dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia is a disabling movement disorder associated with
      the prolonged use of neuroleptic medication. This review, one in a series
      examining the treatment of tardive dyskinesia, will cover miscellaneous
      treatments not covered elsewhere. OBJECTIVES: To determine whether the following
      interventions were associated with a reduction of neuroleptic induced tardive
      dyskinesia: botulin toxin, endorphin, essential fatty acid, EX11582A,
      ganglioside, insulin, lithium, naloxone, oestrogen, periactin, phenylalanine,
      piracetam, stepholidine, tryptophan, neurosurgery, or ECT. SEARCH STRATEGY: The
      initial search of Biological Abstracts (1982-1995), The Cochrane Schizophrenia
      Group's Register (January 1996), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE
      (1966-1995) and PsycLIT (1974-1995) was updated by searching Cochrane
      Schizophrenia Group's Register in July 2002. References of all relevant studies
      were searched for further trial citations. Principal authors of trials were
      contacted. SELECTION CRITERIA: Studies were selected if they focused on people
      with schizophrenia or other chronic mental illnesses, with neuroleptic-induced
      tardive dyskinesia and compared the use of the interventions listed above versus
      placebo or no intervention. DATA COLLECTION AND ANALYSIS: Studies were reliably
      selected, quality assessed and data extracted. Data were excluded where more than
      50% of participants in any group were lost to follow up. For binary outcomes a
      random effects risk ratio (RR) and its 95% confidence interval (CI) was
      calculated. Where possible, the weighted number needed to treat/harm statistic
      (NNT/H), and its 95% confidence interval (CI), was also calculated. For
      continuous outcomes, endpoint data were preferred to change data. Non-skewed data
      from valid scales were to have been synthesised using a weighted mean difference
      (WMD). MAIN RESULTS: Fifty-seven references describing 37 different trials were
      identified by the search strategy. Seven of these were included, 27 excluded, and
      three await assessment. Ceruletide was not clearly more effective than placebo
      (n=132, 2 RCTs, RR not any improvement in tardive dyskinesia 0.82 CI 0.6 to 1.1).
      This also applied to gamma-linolenic acid, although data were sparse (n=16, 1
      RCT, RR no clinical improvement 1.00 CI 0.7 to 1.5), oestrogen (n=12, 1 RCT, RR
      no clinically important improvement 1.2 CI 0.8 to 1.7), and lithium (n=11, 1 RCT,
      RR no clinically important improvement 1.39 CI 0.6 to 3.1). Phenylalanine may
      even be detrimental (n=18, 1 RCT, MD AIMS score 4.40 CI 1.16 to 7.64). One small
      study (n=20) found that insulin was more likely to produce a clinical improvement
      in tardive dyskinesia than placebo (RR no clinical improvement 0.5 CI 0.3 to 0.9,
      NNT 2 CI 1 to 5). REVIEWER'S CONCLUSIONS: There is no strong evidence to support
      the everyday use of any of the agents included in this review. All results must
      be considered inconclusive and these compounds probably should only be used
      within the context of a well-designed evaluative study.

PMID- 12804391
TI  - Interventions for treating trichomoniasis in women.
AB  - BACKGROUND: Around 120 million women worldwide suffer from Trichomonas vaginalis
      vaginitis every year. The infection is sexually transmitted and is believed to
      facilitate HIV transmission. OBJECTIVES: To assess the effects of various
      treatment strategies for trichomoniasis in women. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Trials
      were also identified from reference lists of reviews, through pharmaceutical
      companies, and by informal discovery. Only published data were used in this
      review. Date of the most recent search: November, 2002. SELECTION CRITERIA:
      Randomised or quasi-randomised trials of different treatment strategies in women
      with trichomoniasis. Different antitrichomonal drugs or doses were eligible, as
      were comparisons of treatment with no treatment or placebo. DATA COLLECTION AND
      ANALYSIS: Trial quality was assessed and data extracted by two reviewers
      independently using standard criteria. MAIN RESULTS: Fifty-four trials were
      included. Nitroimidazole drugs seem to be effective in achieving parasitological
      cure in short term follow up. Partner treatment can be effective in decreasing
      longer term reinfection rates. REVIEWER'S CONCLUSIONS: Parasitological cure can
      be achieved by single oral dose of nitroimidazole. Further research should focus
      on developing effective partner treatment strategies to prevent reinfections and
      reduce trichomoniasis prevalence.

PMID- 12804392
TI  - Antibiotics for acute maxillary sinusitis.
AB  - BACKGROUND: For adults seeking care in ambulatory medical practices, sinusitis is
      the most common diagnosis treated with antibiotics. OBJECTIVES: We examined
      whether antibiotics are indicated for acute sinusitis, and if so, which
      antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were
      identified from searches of MEDLINE and EMBASE in December 2001, contacts with
      pharmaceutical companies and bibliographies of included studies. SELECTION
      CRITERIA: Randomized trials were eligible that compared antibiotic to control or
      antibiotics from different classes, for acute maxillary sinusitis. Additional
      criteria for inclusion were diagnostic confirmation by radiograph or sinus
      aspiration, outcomes that included clinical cure or improvement, and a sample
      size of 30 or more adults. Of 2058 potentially relevant studies, two or more
      reviewers identified 49 studies meeting selection criteria. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by two persons and synthesized
      descriptively. Some data were analyzed quantitatively using a random effects
      model. Primary outcomes were: a) clinical cure, and b) clinical cure or
      improvement. Secondary outcomes were radiographic improvement, relapse rates, and
      dropouts due to adverse effects. MAIN RESULTS: Forty-nine trials, involving
      13,660 participants, evaluated antibiotic treatment for acute maxillary
      sinusitis. Major comparisons were antibiotic versus control (n of 5); newer, non
      penicillin antibiotic versus penicillin class (n of 10); and amoxicillin
      clavulanate versus other extended spectrum antibiotics (n of 17), where n is the
      number of trials. Most trials were conducted in otolaryngology settings. Only 8
      trials described adequate allocation and concealment procedures; 20 were double
      blind. Compared to control, penicillin improved clinical cures [relative risk
      (RR) 1.72; 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly
      improve cure rates (RR 2.06; 95% CI 0.65 to 6.53) but there was significant
      variability between studies. Radiographic outcomes were improved by antibiotic
      treatment. Comparisons between classes of antibiotics showed no significant
      differences: newer non-penicillins versus penicillins (RR for cure 1.07; 95% CI
      0.99 to 1.17); newer non-penicillins versus amoxicillin-clavulanate (RR for cure
      1.03; 95% CI 0.96 to 1.11). Compared to amoxicillin-clavulanate, dropouts due to
      adverse effects were significantly lower for cephalosporin antibiotics (RR 0.47;
      95% CI 0.30 to 0.73). Relapse rates within one month of successful therapy were
      7.7%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed
      radiographically or by aspiration, current evidence is limited but supports the
      use of penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the
      moderate benefits of antibiotic treatment against the potential for adverse
      effects.

PMID- 12804393
TI  - Antibiotics for treating bacterial vaginosis in pregnancy.
AB  - BACKGROUND: Bacterial vaginosis is an imbalance of the normal vaginal flora with
      an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary
      flora. Bacterial vaginosis during pregnancy has been associated with poor
      perinatal outcome and, in particular, preterm birth. Identification and treatment
      may reduce the risk of preterm birth and its consequences. OBJECTIVES: To assess
      the effects of antibiotic treatment of bacterial vaginosis in pregnancy. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (September 2002). SELECTION CRITERIA: Randomized trials comparing antibiotic
      treatment with placebo or no treatment, or comparing two or more antibiotic
      regimens in pregnant women with bacterial vaginosis. DATA COLLECTION AND
      ANALYSIS: Two reviewers assessed trials and extracted data independently. Study
      authors were contacted for additional information. MAIN RESULTS: Ten trials
      involving 4249 women were included; all were of good quality. Antibiotic therapy
      was effective at eradicating bacterial vaginosis during pregnancy (odds ratio
      (OR) 0.21, 95% confidence interval (CI) 0.18 to 0.24, eight trials of 3825
      women). Treatment did not significantly reduce the risk of preterm birth before
      37 weeks (OR 0.95, 95% CI 0.82 to 1.10, eight trials of 4062 women), 34 weeks (OR
      1.20, 95% CI 0.69 to 2.07, five trials of 851 women), or 32 weeks (OR 1.08, 95%
      CI 0.70 to 1.68, three trials of 3080 women). However, antibiotic treatment did
      significantly decrease the risk of preterm prelabour rupture of membranes (OR
      0.32, 95% CI 0.15 to 0.67, three trials of 562 women). In women with a previous
      preterm birth, treatment did not affect the risk of subsequent preterm birth (OR
      0.83, 95% CI 0.59 to 1.17, five trials of 622 women) but it did decrease the risk
      of preterm prelabour rupture of membranes (OR 0.14, 95% CI 0.05 to 0.38, two
      trials of 114 women) and low birthweight (OR 0.31, 95% CI 0.13 to 0.75, five
      trials of 622 women). REVIEWER'S CONCLUSIONS: Antibiotic treatment can eradicate
      bacterial vaginosis in pregnancy. However, the current evidence does not support
      screening and treating all pregnant women with asymptomatic bacterial vaginosis
      to prevent preterm birth and its consequences. For women with a previous preterm
      birth, there is little suggestion that detection and treatment of bacterial
      vaginosis will prevent a further preterm birth, but it may reduce the risk of low
      birthweight and preterm prelabour rupture of membranes.

PMID- 12804394
TI  - Chlorpromazine versus placebo for schizophrenia.
AB  - BACKGROUND: Chlorpromazine, formulated in the 1950s, remains a benchmark
      treatment for people with schizophrenia. OBJECTIVES: To evaluate the effects of
      chlorpromazine for schizophrenia in comparison with placebo. SEARCH STRATEGY: We
      updated previous searches of the Cochrane Schizophrenia Group Register (October
      1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2),
      EMBASE (1980-1995), MEDLINE (1966-1995) and PsycLIT (1974-1995), by searching
      Cochrane Schizophrenia Group Register (June 2002). References of all identified
      studies were searched for further trial citations. Pharmaceutical companies and
      authors of trials were contacted. SELECTION CRITERIA: All randomised controlled
      trials (RCTs) comparing chlorpromazine with placebo relevant to people with
      schizophrenia, and non-affective serious/chronic mental illness irrespective of
      mode of diagnosis. Primary outcomes of interest were death, violent behaviours,
      overall improvement, relapse and satisfaction with care. DATA COLLECTION AND
      ANALYSIS: Citations and, where possible, abstracts were inspected independently
      by reviewers, papers ordered, re-inspected and quality assessed. Data were
      extracted by BT and JR. CA and GA independently checked a 10% sample for
      reliability. Dichotomous data were analysed using random effects relative risk
      (RR) and the 95% confidence interval (CI) around this was estimated. Where
      possible the number needed to treat (NNT) or number needed to harm statistics
      (NNH) were calculated. Continuous data were excluded if more than 50% of people
      were lost to follow up, but, where possible, weighted mean difference (WMD) was
      calculated. MAIN RESULTS: Over 1000 electronic records were inspected. The review
      currently mentions 302 papers in its Excluded Studies table and 50 studies in its
      Included Studies table. Four papers are awaiting translation. Chlorpromazine
      reduces relapse over six months to two years (n=512, 3 RCTs, RR 0.65 CI 0.5 to
      0.9, NNT 3 CI 2.5 to 4) and promotes a global improvement in a person's symptoms
      and functioning (n=1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10)
      although the placebo response is also considerable. Fewer people allocated to
      chlorpromazine leave trials early (n=1755, 25 RCTs, RR 0.77 CI 0.6 to 1.1) but
      the difference iss not statistically significant. There are many adverse effects.
      Chlorpromazine is clearly sedating (n=1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6
      CI 5 to 8), it increases a person's chances of experiencing acute movement
      disorders (n=780, 4 RCTs, RR 3.1 CI 1.3 to 7.7, NNH 24 CI 15 to 57), parkinsonism
      (n=1265, 12 RCTs, RR 2.6 CI 1.2 to 5.4, NNH 10 CI 8 to 16) and, perhaps, fits
      (n=695, 3 RCTs, RR 2.4 CI 0.4 to 16). Amongst other things it clearly causes a
      lowering of blood pressure with accompanying dizziness (n=1232, 15 RCTs, RR 1.9
      CI 1.4 to 27, NNH 12 CI 8 to 19) and considerable increases in weight (n=165, 5
      RCTs, RR 4.4 CI 2.1 to 9, NNH 3 CI 2 to 5). REVIEWER'S CONCLUSIONS: This review
      will confirm much that clinicians and recipients of care already know, but
      provides quantification to support clinical impression. Chlorpromazine's global
      position as a 'benchmark' treatment for psychoses is not threatened by this
      review. Chlorpromazine, in common use for half a century, is a well established
      but imperfect treatment. Judicious use of this best available evidence should
      lead to improved evidence-based decision making by clinicians, carers and
      patients.

PMID- 12804395
TI  - Conservative interventions for treating distal radial fractures in adults.
AB  - BACKGROUND: Fracture of the distal radius is a common clinical problem
      particularly in elderly white women with osteoporosis. OBJECTIVES: To determine
      the most appropriate conservative treatment for fractures of the distal radius in
      adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      specialised register (November 2002), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to January week 1
      2003), EMBASE (1988 to 2003 Week 3), CINAHL (1982 to December week 4 2002), the
      National Research Register (up to Issue 4, 2002), PEDro, conference proceedings
      and reference lists of articles. No language restrictions were applied. SELECTION
      CRITERIA: Randomised or quasi-randomised clinical trials involving skeletally
      mature patients with a fracture of the distal radius, which compared commonly
      applied conservative interventions for fracture fixation. These included the
      application of an external support (plaster cast or brace) and fracture
      manipulation. DATA COLLECTION AND ANALYSIS: All trials, judged as fitting the
      selection criteria by both reviewers, were independently assessed by both
      reviewers for methodological quality. Data were extracted for anatomical,
      functional and clinical, including complications, outcomes. The trials were
      grouped into categories relating to manipulation of displaced fractures; use and
      extent, including forearm position, of immobilisation; use of braces; different
      casting materials and techniques; and duration of immobilisation. Although
      quantitative data from some trials are presented, the lack of good quality trials
      and trial heterogeneity inhibited pooling of results. MAIN RESULTS: Three trials
      were newly included in this update. In all, there are 36 trials, involving a
      total of 4114 mainly female and older patients, meeting the inclusion criteria
      for this review. Comprehensive details of the individual trials are provided in
      tabular form, and their results, grouped as indicated above, have been presented
      in text and analyses tables. The poor quality and heterogeneity in terms of
      patient characteristics, interventions compared and outcome measurement, of the
      included trials meant that no meta-analyses were undertaken. REVIEWER'S
      CONCLUSIONS: There remains insufficient evidence from randomised trials to
      determine which methods of conservative treatment are the most appropriate for
      the more common types of distal radial fractures in adults. Therefore, at
      present, practitioners applying conservative management should use an accepted
      technique with which they are familiar, and which is cost-effective from the
      perspective of their provider unit. Patient preferences and circumstances, and
      the risk of complications should also be considered. Prioritising research
      questions to clarify the most appropriate conservative treatment for this common
      fracture is warranted. Researchers should differentiate between extra-articular
      and intra-articular, and non-displaced and displaced fractures, ascertain patient
      preferences, and agree a core outcome data set.

PMID- 12804396
TI  - Risperidone versus typical antipsychotic medication for schizophrenia.
AB  - BACKGROUND: Risperidone is one of the 'new generation' antipsychotics. As well as
      its reputed tendency to cause fewer movement disorders than the older drugs such
      as chlorpromazine and haloperidol, it is claimed that risperidone may improve
      negative symptoms. OBJECTIVES: To evaluate the effects of risperidone for
      schizophrenia in comparison to 'conventional' neuroleptic drugs. SEARCH STRATEGY:
      The original electronic searches of Biological Abstracts (1980-1997), Cochrane
      Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1),
      EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH
      (1997) were updated with a new electronic search of the same databases in 2002.
      The search term used in the update was identical to that used in 1997. Any new
      studies or relevant references were added to the review. In addition, references
      of all identified studies were searched for further trial citations.
      Pharmaceutical companies and authors of trials were also contacted. SELECTION
      CRITERIA: All randomised trials comparing risperidone to any 'conventional'
      neuroleptic treatment for people with schizophrenia or other similar serious
      mental illnesses. DATA COLLECTION AND ANALYSIS: Citations and, where possible,
      abstracts were independently inspected by reviewers, papers ordered, re-inspected
      and quality assessed. Data were also independently extracted. Where possible,
      sensitivity analyses on dose of risperidone, haloperidol and duration of illness
      were undertaken for the primary outcomes of clinical improvement, side effects
      (movement disorders) and acceptability of treatment. For homogeneous dichotomous
      data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate,
      the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat
      basis. MAIN RESULTS: In the short-term, risperidone was more likely to produce an
      improvement in the Positive and Negative Syndrome Scale (PANSS) when compared
      with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT
      8). A similar, favourable outcome for risperidone was found in long-term studies
      (n=859, 2RCTs RR not 20% improved 0.51 CI 0.38 to 0.67 NNT 4;n=675 1RCT, RR not
      improved 40% 0.75 CI 0.66 to 0.84 NNT 5; n=675, 1 RCT, RR not 60% improved 0.90
      CI 0.84 to 0.96, NNT 11). Risperidone was also more likely to reduce relapse at
      one year follow up, compared with haloperidol (n=367, 1 RCT, RR 0.64 CI 0.41 to
      0.99, NNT 7). Less people allocated risperidone left studies before completion,
      both for short-term (n=3066, 16 RCTs, RR 0.76 CI 0.63 to 0.92, NNT 6) and long
      term trials (n=1270, 4RCTs, RR 0.55 CI 0.42 to 0.73 NNT 4). For general movement
      disorders results favoured risperidone. People given risperidone had
      significantly fewer general movement disorders (including extrapyramidal side
      effects) than those receiving older typical antipsychotics (n=2702, 10 RCTs, RR
      0.63 CI 0.56 to 0.71, NNT 3). Significantly fewer people given risperidone used
      antiparkinsonian drugs (n=2524, 11 RCTs, RR 0.66 CI 0.58 to 0.74, NNT 4). As
      regards body weight, however, four studies (n=1708) found people were more likely
      to gain weight if allocated risperidone compared to typical antipsychotics (RR
      1.55 CI 1.25 to 1.93, NNH 3). Risperidone was no more or less likely than
      haloperidol to cause sexual problems such as erectile dysfunction (n=106, 2 RCTs,
      RR 1.55 CI 0.58 to 4.20). Finally, some results found risperidone was more likely
      to cause rhinitis than conventional antipsychotics (n=656, 3 RCTs, RR1.99 CI 1.24
      to 3.19, NNH 3). REVIEWER'S CONCLUSIONS: Risperidone may be more acceptable to
      those with schizophrenia than older antipsychotics and have marginal benefits in
      terms of limited clinical improvement. Its adverse effect profile may be better
      than haloperidol. With the addition of more studies to this review, the
      publication bias evident in previous versions is no longer a significant issue.
      Any marginal benefits this drug may have have to be balanced against its greater
      cost and increased tendency to cause side effects such as weight gain. Recent
      important longer term data favouring risperidone's effect on relapse needs to be
      replicated by researchers independently of the manufacturers of the drug.

PMID- 12804397
TI  - Mannitol for acute traumatic brain injury.
AB  - BACKGROUND: Mannitol is sometimes dramatically effective in reversing acute brain
      swelling, but its effectiveness in the on-going management of severe head injury
      remains open to question. There is evidence that, in prolonged dosage, mannitol
      may pass from the blood into the brain, where it might cause reverse osmotic
      shifts that increase intracranial pressure. OBJECTIVES: To assess the effects of
      different mannitol therapy regimens, of mannitol compared to other intracranial
      pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol
      administration given at other stages following acute traumatic brain injury.
      SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as
      a whole. We checked reference lists of trials and review articles, and contacted
      authors of trials. SELECTION CRITERIA: Randomised trials of mannitol, in patients
      with acute traumatic brain injury of any severity. The comparison group could be
      placebo-controlled, no drug, different dose, or different drug. Trials where the
      intervention was started more than eight weeks after injury, and cross-over
      trials were excluded. DATA COLLECTION AND ANALYSIS: The reviewers independently
      rated quality of allocation concealment and extracted the data. Relative risks
      (RR) and 95% confidence intervals (CI) were calculated for each trial on an
      intention to treat basis. MAIN RESULTS: Overall there were few eligible trials.
      In the pre-operative management of patients with acute intracranial haemorrhage
      the administration of high-dose mannitol resulted in reduced mortality (RR=0.55;
      95%CI 0.36, 0.84) and reduced death and severe disability (RR=0.58; 95%CI 0.45,
      0.74) when compared with conventional-dose mannitol. One trial compared ICP
      directed therapy to 'standard care' (RR for death= 0.83; 95%CI 0.47,1.46). One
      trial compared mannitol to pentobarbital (RR for death = 0.85; 95% CI 0.52,
      1.38). No trials compared mannitol to other ICP-lowering agents. One trial tested
      the effectiveness of pre-hospital administration of mannitol against placebo (RR
      for death=1.75; 95% CI 0.48, 6.38). REVIEWER'S CONCLUSIONS: High-dose mannitol
      appears to be preferable to conventional-dose mannitol in the pre-operative
      management of patients with acute intracranial haematomas. However, there is
      little evidence about the use of mannitol as a continuous infusion in patients
      with raised intracranial pressure in patients who do not have an operable
      intracranial haematoma. Mannitol therapy for raised ICP may have a beneficial
      effect on mortality when compared to pentobarbital treatment. ICP-directed
      treatment shows a small beneficial effect compared to treatment directed by
      neurological signs and physiological indicators. There are insufficient data on
      the effectiveness of pre-hospital administration of mannitol to preclude either a
      harmful or a beneficial effect on mortality.

PMID- 12804398
TI  - Antibiotics for preterm rupture of membranes.
AB  - BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality.
      One cause, associated with preterm rupture of membranes (pROM), is often
      subclinical infection. Maternal antibiotic therapy might lessen infectious
      morbidity and delay labour, but could suppress labour without treating underlying
      infection. OBJECTIVES: To evaluate the immediate and long-term effects of
      administering antibiotics to women with pROM before 37 weeks, on maternal
      infectious morbidity, fetal and neonatal morbidity and mortality, and longer term
      childhood development. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (January 2003) and the Cochrane Controlled
      Trials Register (The Cochrane Library, Issue 4, 2002). SELECTION CRITERIA:
      Randomised controlled trials comparing antibiotic administration with placebo
      that reported clinically relevant outcomes, were included. In addition, trials,
      in which no placebo was used, were included for the outcome of perinatal death
      alone. DATA COLLECTION AND ANALYSIS: Data were extracted from each report without
      blinding of either the results or the treatments that women received. Unpublished
      data were sought from a number of authors. MAIN RESULTS: Nineteen trials
      involving over 6000 women and their babies were included. The use of antibiotics
      following pROM is associated with a statistically significant reduction in
      chorioamnionitis (relative risk (RR) 0.57, 95% confidence interval (CI) 0.37 to
      0.86). There was a reduction in the numbers of babies born within 48 hours (RR
      0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (RR 0.80, 95% CI 0.71
      to 0.90). The following markers of neonatal morbidity were reduced: neonatal
      infection (RR 0.68, 95% CI 0.53 to 0.87), use of surfactant (RR 0.83, 95% CI 0.72
      to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral
      ultrasound scan prior to discharge from hospital (RR 0.82, 95% CI 0.68 to 0.98).
      Co-amoxiclav was associated with an increased risk of neonatal necrotising
      enterocolitis (RR 4.60, 95% CI 1.98 to 10.72). REVIEWER'S CONCLUSIONS: Antibiotic
      administration following pROM is associated with a delay in delivery and a
      reduction in major markers of neonatal morbidity. These data support the routine
      use of antibiotics in pPROM. The choice as to which antibiotic would be preferred
      is less clear as, by necessity, fewer data are available. Co-amoxiclav should be
      avoided in women at risk of preterm delivery because of the increased risk of
      neonatal necrotising enterocolitis. From the available evidence, erythromycin
      would seem a better choice.

PMID- 12804399
TI  - Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: Rebleeding is an important cause of death and disability in people
      with aneurysmal subarachnoid haemorrhage. Rebleeding is probably due to
      dissolution of the clot by natural fibrinolytic activity. OBJECTIVES: The
      objective of this review was to assess the effect of antifibrinolytic treatment
      in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register, the Cochrane Controlled
      Trials Register, Medline and Embase (last searched June 2002) and reference lists
      of articles. We also contacted drug companies. SELECTION CRITERIA: Randomised
      trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid,
      epsilon amino-caproic acid or an equivalent) with control in people with
      confirmed subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion and extracted the data. All five
      reviewers assessed trial quality. MAIN RESULTS: Nine trials involving 1399
      patients were included. Based on 1041 patients in three trials, antifibrinolytic
      treatment did not show any evidence of benefit for poor outcome (death,
      vegetative state or severe disability) with an odds ratio of 1.12, 95% confidence
      interval 0.88 to 1.43. Death from all causes was not significantly influenced by
      treatment across all nine trials (odds ratio 0.99, 95% confidence interval 0.79
      to 1.24). Antifibrinolytic treatment reduced the risk of re-bleeding reported at
      the end of follow-up, with some heterogeneity between the trials (odds ratio
      0.55, 95% confidence interval 0.42 to 0.71). Treatment increased the risk of
      cerebral ischaemia in five trials (odds ratio 1.39, 95% confidence interval 1.07
      to 1.82) with considerable heterogeneity between the most recent study (Roos
      2000), in which specific treatments to prevent cerebral ischemia were used, and
      the four older studies. Antifibrinolytic treatment showed no effect on the
      reported rate of hydrocephalus in five trials (odds ratio 1.14, 95% confidence
      interval 0.86 to 1.51). REVIEWER'S CONCLUSIONS: Treatment does not improve
      clinical outcome because the benefit is offset by an increase in poor outcome
      caused by cerebral ischemia as a result of treatment with antifibrinolytics.
      These data do not support the routine use of antifibrinolytic drugs in the
      treatment of patients with aneurysmal subarachnoid haemorrhage.

PMID- 12804400
TI  - Polyunsaturated fatty acid supplementation for schizophrenia.
AB  - BACKGROUND: Limited evidence supports a hypothesis suggesting that schizophrenic
      symptoms may be the result of altered neuronal membrane structure and metabolism.
      This structure and metabolism is dependent on blood plasma levels of certain
      essential fatty acids and their metabolites. OBJECTIVES: To review the effects
      polyunsaturated fatty acids for people with schizophrenia. SEARCH STRATEGY: The
      initial search of 1998 was updated. We searched the Cochrane Schizophrenia
      Group's Register (July 2002), and authors of included studies and relevant
      pharmaceutical companies were contacted. SELECTION CRITERIA: All randomised
      clinical trials of polyunsaturated fatty acid treatment for schizophrenia. DATA
      COLLECTION AND ANALYSIS: Reviewers, working independently, selected, quality
      assessed, and extracted relevant data. Analysis was on an intention-to-treat
      basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence
      intervals (CI) were calculated and the number needed to treat (NNT) estimated.
      For continuous data, weighted mean differences (WMD) and their 95% confidence
      intervals were calculated. Data were inspected for heterogeneity. MAIN RESULTS:
      Five short small studies (n=313) were included. One small study (n=30) suggested
      that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some
      antipsychotic properties when compared with placebo, even if not given as a
      supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to
      1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to
      29). Other studies comparing omega-3 EFA's with placebo as a supplement to
      antipsychotics were too small to be conclusive. There was a suggestion that
      people already on antipsychotics when given omega-3 EFA supplementation had
      greater improvement of mental state compared to those receiving a placebo
      supplementation but the result were not significant (n=29, 1 RCT, RR <25%
      improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both
      medicated and un-medicated patients was significantly better for those receiving
      omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39
      to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group
      (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low
      attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to
      2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic
      acid enriched oil and docosahexanoic acid oil, also found no differences between
      these two EFA's in measures of mental state. One small (n=16) study investigated
      the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and
      found no clear effects. There is not a clear dose response to omega-3
      supplementation. Adverse effects seem rare but diarrhoea may be a problem in the
      medium term. REVIEWER'S CONCLUSIONS: The use of omega-3 polyunsaturated fatty
      acids for schizophrenia remains experimental and large well designed, conducted
      and reported studies are indicated and needed.

PMID- 12804401
TI  - Inhaled short acting beta2-agonist use in chronic asthma: regular versus as
      needed treatment.
AB  - BACKGROUND: Inhaled short-acting beta-2 agonists are the major class of
      bronchodilators used for relief of symptoms in asthma. There has been concern
      that excessive uncontrolled use of beta-2 agonists might have contributed to
      rises in asthma mortality seen in some countries. International consensus
      guidelines now generally recommend using short-acting beta-2 agonists only for
      relief of symptoms on an as needed basis. OBJECTIVES: To assess the effects of
      using short-acting inhaled beta-2 agonists regularly or only on demand in
      asthmatic adults and children on indices of asthma control. SEARCH STRATEGY:
      Searches were carried out of the Cochrane Airways Group "Asthma and Wheez* RCT"
      register in 1997, 1999 and 2002. Pharmaceutical companies and researchers with an
      interest in the area were asked directly for details of any studies that they
      knew of. SELECTION CRITERIA: Randomised controlled trials in which the short
      acting beta-2 agonist was given regularly in the experimental group, together
      with an inhaled bronchodilator for relief of symptoms ('rescue use'). The control
      group consisted of matching placebo inhaled regularly, with an inhaled
      bronchodilator for 'rescue use'. DATA COLLECTION AND ANALYSIS: Data were
      extracted and quality assessments were made by both reviewers. Parallel group and
      cross-over trials were analysed separately. Where possible data were pooled using
      a fixed effects model. MAIN RESULTS: 800 abstracts were identified for the first
      version and 60 papers were requested for full assessment. In this update 15
      studies were added to the 34 trials which met the entry criteria for the first
      version in 2000. No clinically or statistically significant differences were
      found in airway calibre measurements. The regular treatment groups required less
      rescue medication, -0.80 puffs/24 hours (95% CI -0.07 to -1.30) and -0.42
      puffs/daytime (95% CI -0.12 to -0.72), and had fewer days with asthma symptoms, 
      6.7% (95% CI -2.7 to -10.7). There was no significant difference in the odds
      ratio for the occurrence of at least one major asthma exacerbation either in
      parallel group or cross over studies. REVIEWER'S CONCLUSIONS: In general, these
      results support current guidelines, although it has given reassuring evidence
      against concerns over regular use of inhaled short-acting beta-2 agonists.

PMID- 12804402
TI  - Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
AB  - BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary
      disease (COPD) may suffer recurrent exacerbations with an increase in volume
      and/or purulence of sputum and any therapy that reduced the number of
      exacerbations would be useful. There is a marked difference between countries in
      terms of prescribing of mucolytics depending on whether or not they are perceived
      to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults
      with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the
      Cochrane Airways Group trials register and reference lists of articles, on three
      separate occasions. SELECTION CRITERIA: Randomised trials that compared oral
      mucolytic therapy with placebo for at least two months in adults with chronic
      bronchitis or COPD. Studies of people with asthma and cystic fibrosis were
      excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study
      authors and drug companies were contacted for missing information. MAIN RESULTS:
      Twenty three trials were included. Compared with placebo, there was a significant
      reduction in the number of exacerbations per patient with oral mucolytics
      (weighted mean difference (WMD) -0.066 per month, 95% confidence interval -0.077,
      -0.054, p<0.001). Using the annualised rate of exacerbations in the control
      patients of 2.7 per year, this is a 29% reduction. The number of days of
      disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35, p<0.001).
      The number of patients who remained exacerbation-free was greater in the
      mucolytic group (OR 2.22, 95% confidence interval 1.93, 2.54, p<0.001). There was
      no difference in lung function or in adverse effects reported between treatments.
      REVIEWER'S CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment
      with mucolytics was associated with a small reduction in acute exacerbations and
      a somewhat greater reduction in total number of days of disability.

PMID- 12804403
TI  - Intra-cytoplasmic sperm injection versus conventional techniques for oocyte
      insemination during in vitro fertilisation in patients with non-male
      subfertility.
AB  - BACKGROUND: In vitro fertilisation (IVF) as treatment for male factor
      subfertility is associated with lower fertilisation and pregnancy rates than for
      other indications. Since the late 1980s several assisted fertilisation techniques
      have emerged and have been rapidly developed to try to enhance results for
      couples with male factor subfertility, or to help couples with severe male factor
      for whom conventional IVF was not possible. The techniques of partial zona
      dissection (PZD) and of subzonal microinjection of spermatozoa into the
      perivitelline space (SUZI) are by far surpassed by the technique of intra
      cytoplasmatic sperm injection (ICSI). ICSI has proven to be the therapy of choice
      for couples with severe male factor subfertility. OBJECTIVES: To investigate
      whether ICSI improves livebirth rate in comparison to IVF in couples with non
      male subfertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders
      and Subfertility Group trials register (searched 30 May 2002), the Cochrane
      Controlled Trials Register (Cochrane Library Issue 2, 2002), PubMed (January 1992
      to July 2002) and reference lists of articles. SELECTION CRITERIA: Trials were
      included if they compared the effects of these techniques on livebirths,
      pregnancy and fertilisation outcomes. Only randomised studies were included in
      this review. DATA COLLECTION AND ANALYSIS: One study met the inclusion criteria
      for this review. The study compared ICSI with IVF within couples with non-male
      infertility. Data was extracted independently by two reviewers. MAIN RESULTS:
      There were no randomised data comparing livebirth rates. The single identified
      study did not find a difference in pregnancy rates (OR 1.4, 95% CI 0.95 to 2.2).
      There were no randomised data on miscarriage rates, or on other adverse events
      such as congenital malformations that may be of concern. REVIEWER'S CONCLUSIONS:
      Whether ICSI should be preferred to IVF for cases of non-male factor subfertility
      remains an open question. Further research should report livebirth rates and
      adverse events.

PMID- 12804404
TI  - Aminopyridines for symptomatic treatment in multiple sclerosis.
AB  - BACKGROUND: The potassium channel blockers 4-aminopyridine (AP) and 3,4
      diaminopyridine (DAP) increase nerve conduction in demyelinated nerve fibers, and
      have been proposed as a symptomatic therapy for people with multiple sclerosis
      (MS). OBJECTIVES: To determine the efficacy and safety of aminopyridines for
      neurological deficits in MS people. SEARCH STRATEGY: We searched CENTRAL (Issue
      2, 2002), MEDLINE (January 1966-July 2002), EMBASE (1974-July 2002), and the
      Cochrane MS Group's Specialised Register. We hand searched bibliographic
      references from retrieved studies and recent MS symposia reports, and contacted
      known studies' investigators. SELECTION CRITERIA: We included trials fulfilling
      all following criteria: randomised controlled trials (RCTs); adults with MS, out
      of exacerbation; AP or DAP treatment versus placebo; clinical endpoints. DATA
      COLLECTION AND ANALYSIS: We identified 26 potentially pertinent studies. Three
      reviewers independently extracted data and assessed trial quality from 17 full
      paper studies. MAIN RESULTS: Six studies (eight publications, 198 participants,
      all crossover trials) were considered. Five studies assessed the efficacy of AP
      versus placebo, one compared DAP with active placebo. Treatment duration ranged
      from hours to six months. Median quality score of the studies was 3.
      Heterogeneity of outcome assessment and absence of information on individual
      study periods allowed quantitative pooling of results for few categorical
      variables. Of the 198 treated patients, there were six major side effects: one
      acute encephalopathy, three episodes of confusion, and two seizures. Three
      studies (54 patients) assessed manual muscle testing, with 29 patients (54%)
      improving in at least one muscular district during study treatment versus four
      patients (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI]
      4.7-43.7). Nine out of 54 participants (17%) improved in ambulation during study
      treatment versus none during placebo (p<0.001). A lower EDSS score was found in
      13/198 participants during study treatment (7%) versus none during placebo
      (p<0.001). No improvement in neuropsychological tests was found in three trials
      assessing cognitive function. Finally, 47/136 MS people (35%) felt better when
      receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3-22.0).
      REVIEWER'S CONCLUSIONS: Currently available information allows no unbiased
      statement about safety or efficacy of aminopyridines for treating MS symptoms.
      Furthermore, we could not obtain any data on three unpublished RCTs (more than
      300 participants). We conclude that publication bias remains a pervasive problem
      in this area, and that until the results of these unpublished studies are
      available to the scientific community, no confident estimate of effectiveness of
      aminopyridines in the management of MS symptoms is possible.

PMID- 12804405
TI  - Naltrexone maintenance treatment for opioid dependence.
AB  - BACKGROUND: Despite widespread use of naltrexone maintenance in many countries
      for more than a decade, the evidence of its effects has not yet been
      systematically evaluated. OBJECTIVES: To evaluate the effects of naltrexone
      maintenance treatment in preventing relapse in opioid addicts after
      detoxification. SEARCH STRATEGY: We searched MEDLINE (1973-first year of
      naltrexone use in humans-July 2000), EMBASE (1974-July 2000), Cochrane Controlled
      Trials Register (Cochrane Library issue 2001.4) and handsearched the "Bolletino
      per le Farmacodipendenze e l'Alcolismo" (1978 to 1997) and reference lists of
      relevant articles. We contacted pharmaceutical producers of naltrexone, authors
      and other Cochrane review groups. Date of most recent searches: February 2003.
      SELECTION CRITERIA: All controlled studies of naltrexone; treatment of heroin
      addicts after detoxification. DATA COLLECTION AND ANALYSIS: Reviewers evaluated
      data independently and analysed outcome measures taking into consideration
      adherence to and success of the study intervention. Data were extracted and
      analysed stratifying for the three categories of study quality. Where possible,
      meta-analysis was performed. MAIN RESULTS: Eleven studies met the criteria for
      inclusion in this review, even if not all of them were randomised. The
      methodological quality of the included studies varied, but was generally poor.
      Meta-analysis could be performed to a very low degree only, because the studies
      and their outcome measures were very heterogeneous. A statistically significant
      reduction of (re-)incarcerations was found for patients treated with naltrexone
      and behaviour therapy in respect to those treated with behaviour therapy only.
      The other outcomes considered in the meta-analysis did not yield any significant
      results. Final conclusions on whether naltrexone treatment may be considered
      effective in maintenance therapy cannot be drawn from the clinical trials
      available so far. REVIEWER'S CONCLUSIONS: The available trials do not allow a
      final evaluation of naltrexone maintenance treatment yet. A trend in favour of
      treatment with naltrexone was observed for certain target groups (particularly
      people who are highly motivated), as has been previously described in the
      literature.

PMID- 12804406
TI  - Oestrogens for urinary incontinence in women.
AB  - BACKGROUND: It is possible that oestrogen deficiency may be an aetiological
      factor in the development of urinary incontinence in women. OBJECTIVES: To assess
      the effects of oestrogens used for the treatment of urinary incontinence. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group trials register (November
      2002) and the reference lists of relevant articles. Date of the most recent
      searches: November 2002. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials that included oestrogens in at least one arm, in women with
      symptomatic or urodynamic diagnoses of stress, urge or mixed incontinence or
      other urinary symptoms. DATA COLLECTION AND ANALYSIS: Trials were evaluated for
      methodological quality and appropriateness for inclusion by the reviewers. Data
      were extracted by all three reviewers and cross checked. Trial results were
      analysed within clinical subgroups or by intervention. Where appropriate, meta
      analysis was undertaken. MAIN RESULTS: Twenty eight trials were identified which
      included 2926 women. Sample sizes ranged from 16 to 1525. The trials used varying
      combinations of type of oestrogen, dose, duration of treatment and length of
      follow up. Outcome data were not reported consistently and were available for
      only a minority of trials. In the 15 trials that compared oestrogen with placebo,
      374 women received oestrogen and 344 placebo. Subjective impression of cure was
      higher amongst those treated with oestrogen for all categories of incontinence
      (36/101, 36% versus 20/96, 21%; RR for cure 1.61, 95% CI: 1.04 to 2.49). When
      subjective cure and improvement were considered together, a statistically higher
      cure and improvement rate was shown for both urge (35/61, 57% versus 16/58, 28%
      on placebo) and stress (46/107, 43% versus 29/109, 27%) incontinence. For women
      with urge incontinence, the chance of cure or improvement was approximately a
      quarter higher again than in women with stress incontinence. Taking all trials
      together, the data suggested that about 50% of women treated with oestrogen were
      cured or improved compared with about 25% on placebo. Overall, there were around
      1 to 2 fewer voids in 24 hours amongst women treated with oestrogen. The effect
      again appeared to be larger amongst women with urge incontinence. There were no
      statistically significant differences in respect of frequency, nocturia or
      urgency. No serious adverse events were reported although some women experienced
      vaginal spotting, breast tenderness or nausea. In a large trial conducted amongst
      women with heart disease, data from a subset who had incontinence suggested that
      women treated with a combination of oestrogen and a progestogen had lower
      subjective cure or improvement rates compared to the placebo group (RR 0.85, 95%
      CI 0.76 to 0.95). The data were too few to address other questions about
      oestrogens compared with, or in combination with, other treatments, different
      types of oestrogen or different modes of delivery. REVIEWER'S CONCLUSIONS:
      Oestrogen treatment can improve or cure incontinence and the evidence suggests
      that this is more likely with urge incontinence. There was little evidence from
      the trials after oestrogen treatment had finished and none about long-term
      effects. Combined oestrogen and progesterone appeared to reduce the likelihood of
      cure or improvement. There were too few data to address reliably other aspects of
      oestrogen therapy such as oestrogen type, dose and route of administration.
      However, the risk of endometrial and breast cancer after long-term use suggests
      that oestrogen treatment should be for limited periods, especially in women with
      an intact uterus.

PMID- 12804407
TI  - Decision aids for people facing health treatment or screening decisions.
AB  - BACKGROUND: Decision aids prepare people to participate in preference-sensitive
      decisions. OBJECTIVES: 1. Create a comprehensive inventory of patient decision
      aids focused on healthcare options. 2. Review randomized controlled trials (RCT)
      of decision aids, for people facing healthcare decisions. SEARCH STRATEGY:
      Studies were identified through databases and contact with researchers active in
      the field. SELECTION CRITERIA: Two independent reviewers screened abstracts for
      interventions designed to aid patients' decision making by providing information
      about treatment or screening options and their associated outcomes. Information
      about the decision aids was compiled in an inventory; those that had been
      evaluated in a RCT were reviewed in detail. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently extracted data using standardized forms. Results of RCTs
      were pooled using weighted mean differences (WMD) and relative risks (RR) using a
      random effects model. MAIN RESULTS: Over 200 decision aids were identified. Of
      the 131 available decision aids, most are intended for use before counselling.
      Using the CREDIBLE criteria to evaluate the quality of the decision aids: a) most
      included potential harms and benefits, credentials of the developers, description
      of their development process, update policy, and were free of perceived conflict
      of interest; b) many included reference to relevant literature; c) few included a
      description of the level of uncertainty regarding the evidence; and d) few were
      evaluated. Thirty of these decision aids were evaluated in 34 RCTs and another
      trial evaluated a suite of eight decision aids. An additional 30 trials are yet
      to be published. Among the trials comparing decision aids to usual care, decision
      aids performed better in terms of: a) greater knowledge (WMD 19 out of 100, 95%
      CI: 13 to 24; b) more realistic expectations (RR 1.4, 95%CI: 1.1 to 1.9); c)
      lower decisional conflict related to feeling informed (WMD -9.1 of 100, 95%CI: 
      12 to -6); d) increased proportion of people active in decision making (RR 1.4,
      95% CI: 1.0 to 2.3); and e) reduced proportion of people who remained undecided
      post intervention (RR 0.43, 95% CI: 0.3 to 0.7). When simpler were compared to
      more detailed decision aids, the relative improvement was significant in: a)
      knowledge (WMD 4 out of 100, 95% CI: 3 to 6); b) more realistic expectations (RR
      1.5, 95% CI: 1.3 to 1.7); and c) greater agreement between values and choice.
      Decision aids appeared to do no better than comparisons in affecting satisfaction
      with decision making, anxiety, and health outcomes. Decision aids had a variable
      effect on which healthcare options were selected. REVIEWER'S CONCLUSIONS: The
      availability of decision aids is expanding with many on the Internet; however few
      have been evaluated. Trials indicate that decision aids improve knowledge and
      realistic expectations; enhance active participation in decision making; lower
      decisional conflict; decrease the proportion of people remaining undecided, and
      improve agreement between values and choice. The effects on persistence with
      chosen therapies and cost-effectiveness require further evaluation. Finally,
      optimal strategies for dissemination need to be explored.

PMID- 12804408
TI  - Antibiotics versus placebo for prevention of postoperative infection after
      appendicectomy.
AB  - BACKGROUND: Appendicitis is the most common cause of acute abdominal pain
      requiring surgical intervention. The cause of appendicitis is unclear and the
      mechanism of pathogenesis continues to be debated. Despite improved asepsis and
      surgical techniques, postoperative complications, such as wound infection and
      intraabdominal abscess, still account for a significant morbidity. Several
      studies implicate that postoperative infections are reduced by administration of
      antimicrobial regimes. OBJECTIVES: The objective of this review is to evaluate
      the use of antibiotics with placebo or no treatment in patients undergoing
      appendectomy. Will these patients benefit from antimicrobial prophylaxis? The
      outcomes are described according to the nature of the appendix, as either simple
      appendicitis (including the non-infectious stage) and complicated appendicitis.
      This review do not attempt to compare the effect of different regimens. That
      clinical question is addressed in another review undertaken by Bleuer 1999.
      SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register (Cochrane
      Library 2002 issue 4); Pubmed, Embase and the Cochrane Colorectal Cancer Group
      Specialised Register (Up to October 2002). In addition we manually searched the
      reference lists of the primary identified trials. SELECTION CRITERIA: We
      evaluated Randomised Controlled Trials (RCTs) and Controlled Clinical Trials
      (CCTs) in which any antibiotic regime were compared to placebo in patients
      suspected of having appendicitis, and undergoing appendectomy. Both studies on
      children and adults were reviewed. The outcome measures of the studies were:
      Wound infection, intra abdominal abscess, length of stay in hospital, and
      mortality. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were
      assessed, recorded and cross-checked by two reviewers. MAIN RESULTS: Forty-five
      studies including 9576 patients were included in this review. The overall result
      is that the use of antibiotics is superior to placebo for preventing wound
      infection and intraabdominal abscess, with no apparent difference in the nature
      of the removed appendix. Studies exclusively on children and studies examining
      topical application reported results in favour to the above although the results
      were not significant. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis is effective
      in the prevention of postoperative complications in appendectomised patients,
      whether the administration is given pre-, peri- or post-operatively, and could be
      considered for routine in emergency appendectomies.

PMID- 12804409
TI  - Iron chelating agents for treating malaria.
AB  - BACKGROUND: Researchers are exploring the effects of adding treatments to the
      main antimalarial regimens in an attempt to reduce mortality from Plasmodium
      falciparum. Iron chelation is one potential chemotherapeutic adjuvant treatment.
      Before advocating adjunctive therapy, the effects of iron chelators in improving
      patient outcomes need to be examined. OBJECTIVES: To assess the effects of iron
      chelating agents combined with antimalarial drugs, or iron chelators alone, for
      treating Plasmodium falciparum malaria in adults and children, in relation to
      mortality, coma recovery time, parasite clearance, and adverse effects. SEARCH
      STRATEGY: We searched the Cochrane Infectious Diseases Group trials register (up
      to January 2003), the Cochrane Central Register of Controlled Trials (Cochrane
      Library, Issue 1, 2003), MEDLINE (January 1966 to January 2003), EMBASE (January
      1980 to November 2002), and reference lists of retrieved studies. We also
      contacted organisations, experts and researchers in the field. SELECTION
      CRITERIA: All randomised controlled trials comparing iron chelating agents with
      placebo, or comparing iron chelating agents in conjunction with other
      antimalarials with antimalarial treatment alone in adults or children with
      falciparum malaria. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      applied inclusion criteria and assessed trial quality. One reviewer (HS)
      extracted data from included studies. Study authors were contacted for missing
      and additional data. MAIN RESULTS: Seven trials involving 570 participants were
      included. Two trials involving 435 children compared the iron chelator DFO with
      placebo and standard treatment. No evidence of benefit or harm was shown in
      relation to mortality, but studies were small. The risk of experiencing
      persistent seizures was lower with DFO compared to placebo treatment (RR 0.80,
      95% CI 0.67 to 0.95), but adverse effects were more common in the DFO group. One
      trial involving 45 adults and children compared the orally active iron chelator
      (deferiprone) with placebo and standard treatment; coma recovery (WMD -27 hrs;
      95%CI -34.20 to -19.80) and parasite clearance (WMD -24 hrs; 95%CI -35.27 to 
      12.73) were significantly faster in the deferiprone group compared to placebo,
      but clinical significance cannot be assumed from this small trial. The authors
      reported no side effects during the study. REVIEWER'S CONCLUSIONS: There are
      insufficient data for any conclusions for both agents tested. There are non
      significant trends towards harm (death) and potential benefit (fewer seizures)
      with DFO. With deferiprone, results suggest possible benefit (shorter coma
      recovery and parasite clearance). If this topic is considered a priority for
      further research, larger trials are needed to detect an effect on clinical
      outcomes; and these trials should also include carefully evaluate adverse
      effects.

PMID- 12804410
TI  - Gastro-oesophageal reflux treatment for asthma in adults and children.
AB  - BACKGROUND: Asthma and gastro-oesophageal reflux are both common medical
      conditions and often co-exist. Studies have shown conflicting results concerning
      the effects of lower oesophageal acidification as a trigger of asthma.
      Furthermore, asthma might precipitate gastro-oesophageal reflux. Thus a temporal
      association between the two does not establish that gastro-oesophageal reflux
      triggers asthma. Randomised trials of a number of treatments for gastro
      oesophageal reflux in asthma have been conducted to determine whether treatment
      of reflux improves asthma. OBJECTIVES: The objective of this review was to
      evaluate the effectiveness of treatments for gastro-oesophageal reflux in terms
      of their benefit on asthma. SEARCH STRATEGY: The Cochrane Airways Group trials
      register, review articles and reference lists of articles were searched.
      SELECTION CRITERIA: Randomised controlled trials of treatment for oesophageal
      reflux in adults and children with a diagnosis of both asthma and gastro
      oesophageal reflux. DATA COLLECTION AND ANALYSIS: Trial quality and data
      extraction were carried out by two independent reviewers. Authors were contacted
      for confirmation or more data. MAIN RESULTS: Twelve trials met the inclusion
      criteria. Interventions included proton pump inhibitors (n=6), histamine
      antagonists (n=5), surgery (n=1) and conservative management (n=1). Treatment
      duration ranged from 1 week to 6 months. A temporal association between asthma
      and gastro-oesophageal reflux was investigated in 4 trials and found to be
      present in a proportion of participants in these trials. Anti-reflux treatment
      did not consistently improve lung function, asthma symptoms, nocturnal asthma or
      the use of asthma medications. REVIEWER'S CONCLUSIONS: In asthmatic subjects with
      gastro-oesophageal reflux, (but who were not recruited specifically on the basis
      of reflux-associated respiratory symptoms), there was no overall improvement in
      asthma following treatment for gastro-oesophageal reflux. Subgroups of patients
      may gain benefit, but it appears difficult to predict responders.

PMID- 12804411
TI  - Recordings or summaries of consultations for people with cancer.
AB  - BACKGROUND: Many people find it difficult to remember information provided during
      medical consultations. One way of improving this may be to provide a record of
      the conversation. OBJECTIVES: This review examined the effects of providing
      recordings or summaries of their consultations to people with cancer and their
      families. SEARCH STRATEGY: We searched the following sources: The Cochrane
      Library (issue 4 2002); MEDLINE (1966 to January week 1 2003); CINAHL (1982 to
      December week 4 2002); Dissertation Abstracts (1861 to week 2 2003); EMBASE (1985
      to week 2 2003); PsycINFO (1967 to January week 2 2003); AMED (1985 to December
      2002); and Sociological Abstracts (1998 to week 2 2003). For the initial (1999)
      publication of this review we also searched the following databases: Sociofile;
      Cancerlit; IAC Health & Wellness; JICST; Pascal; ERIC; ASSIA; Linguistics and
      Language Behavior Abstracts; Mental Health Abstracts; CAB Health; DHSS-Data;
      MANTIS. SELECTION CRITERIA: Randomised and non-randomised controlled trials that
      evaluate the effects of providing recordings (e.g. audiotapes) or summaries (e.g.
      letter with reminders of key points) of consultations to people with cancer or
      their families. Two reviewers assessed studies for inclusion. DATA COLLECTION AND
      ANALYSIS: Data were extracted by one reviewer and checked by another reviewer.
      The quality of studies was assessed on six criteria. MAIN RESULTS: Twelve studies
      satisfied the selection criteria. All involved adult participants. The studies
      did not all measure similar outcomes. In seven studies, between 83% and 96% of
      participants found recordings or summaries of their consultations valuable. Five
      out of nine studies reported better recall of information for those receiving
      recordings or summaries. Four out of seven studies found that participants
      provided with a recording or summary were more satisfied with the information
      received. No studies (out of seven) found any statistically significant effect on
      anxiety or depression. One study evaluated the effects on quality of life, but
      found no main effects. No study evaluated the effects on survival. REVIEWER'S
      CONCLUSIONS: The provision of recordings or summaries of key consultations may
      benefit most adults with cancer. Although more research is needed to improve our
      understanding of these interventions, most patients find them very useful.
      Practitioners should consider offering people tape recordings or written
      summaries of their consultations

PMID- 12804412
TI  - Mechanical bowel preparation for elective colorectal surgery.
AB  - BACKGROUND: For more than a century the presence of bowel content during surgery
      has been related to anastomotic leakage. Mechanical bowel preparation has been
      considered an efficient agent against leakage and infections complications. This
      dogma is not based on solid evidence, but more on observational data and expert's
      opinions. OBJECTIVES: To determine the security and effectiveness of prophylactic
      mechanical bowel preparation for morbidity and mortality rates in colorectal
      surgery. The following hypothesis was tested: "The use of mechanical bowel
      preparation before elective colorectal surgery reduces the incidence of
      postoperative complications". SEARCH STRATEGY: All publications describing
      mechanical bowel preparation before elective colorectal surgery was sought
      through computerized searches of EMBASE, LILACS, MEDLINE, and Cochrane Library;
      by hand-searching in relevant medical journals, from major gastroenterological
      congresses, without limitation for date and language, using the search strategy
      described by the Colorectal Cancer Review Group. In addition, randomised clinical
      trials will be searched through personal communication with colleagues and from
      conference proceedings SELECTION CRITERIA:  STUDIES: All randomised, clinical
      trials, that were performed in order to answer the hypothesis. PARTICIPANTS:
      Patients submitted elective colorectal surgery. INTERVENTIONS: Any strategy in
      mechanical bowel preparation compared with no mechanical bowel preparation.
      PRIMARY OUTCOME MEASURES: 1. Anastomosis leakage- stratified for rectum and colon
      2. Overall anastomotic leakage SECONDARY OUTCOME MEASURES: 3. Mortality 4.
      Peritonitis 5. Re operation 6. Wound Infection 7 Infectious extra-abdominal
      complication 8. Non-infection extra-abdominal 9. Overall surgical site infections
      DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers
      and cross-checked. The methodological quality of each trial was assessed by the
      same two reviewers. Details of the randomisation (generation and concealment),
      blinding, whether an intention-to-treat analysis was done, and the number of
      patients lost to follow-up was recorded. The results of each RCT was summarised
      in 2 x 2 tables for each outcome. For analysis the Peto-Odds ratio was used as
      defaults (no statistical heterogeneity was observed) MAIN RESULTS: Of the 1159
      patients with anastomosis (6 RCTs), 576 were allocated for mechanical bowel
      preparation (groups 1) and 583 for no preparation (groups 2) before elective
      colorectal surgery. Of 1204 patients totally enrolled 595 were in groups 1 and
      609 in groups 2. PRIMARY OUTCOMES: 1) Anastomotic leakage - stratified:A) Low
      anterior resection: 12.5% (6 of 48 patients in 1) compared with 12% (6 of 50
      patients in 2); Peto OR 1.17, 95% CI: 0.35 - 3.96 (non-significant) B) Colonic
      surgery: 1.16% (2 of 172 patients in 1) compared with 0.6% (1 of 166 patients in
      2); Peto OR 1.75, 95% CI: 0.18 - 17.02 2) Overall anastomotic leakage: 5.5% (32
      of 576 patients in 1) compared with 2.9% (17 of 583 patients in 2); Peto OR 1.94,
      95% CI: 1.09 - 3.43 (P=0.02) SECONDARY OUTCOMES: 3) Mortality: 0.6% (2 of 329
      patients in 1) compared with 0% (0 of 326 patients in 2); Peto OR 7.95, 95% CI:
      0.49 - 128.34 (non-significant) 4) Peritonitis: 5.1% ( 13 of 254 patients in 1)
      compared with 2.8% (7 of 252 patients in 2); Peto OR 1.90, 95% CI: 0.78 -4.64)
      (non significant) 5) Reoperation: 3.3% ( 11 of 329 patients) compared with 2.5%
      (8 of 326 patients); Peto OR 1.40, 95% CI: 0.56 - 3.49) (non-significant) 6)
      Wound infection: 7.4% (44 of 595 patients in 1) compared with 5.7% (35 of 609
      patients in 2); Peto OR 1.34, 95% CI: 0.85 - 2.13 (non-significant) 7) Infectious
      extra-abdominal complication: 8.3% ( 14 of 168 patients in 1) compared with 9.4%
      (15 of 159 patients in 2); Peto OR, 95%: 0.87 (0.41 - 1.87) 8) Non-infection
      extra-abdominal complication: 8.0% ( 20 of 250 patients in 1) compared with 7.0%
      (17 of 246 patients in 2); Peto OR 1.19, 95% CI: 0.61 - 2.32 (non-significant) -
      9) Surgical site infection: 9.8% (31 of 325 patients in 1) compared with 8.3% (27
      of 322 patients in 2); Peto OR 1.20, 95% CI: 0.70 - 2.05 (non-significant) -
      REVIEWER'S CONCLUSIONS: The results failed to support the hypothesis that bowel
      preparation reduces anastomotic leak rates and other complications. There was no
      a priori hypothesis that bowel preparation may increase anastomotic leak rates,
      so this was not stated. Thus, the routine use of mechanical bowel preparation in
      patients undergoing elective colorectal surgery is questioned.

PMID- 12804413
TI  - Internal fixation versus arthroplasty for intracapsular proximal femoral
      fractures in adults.
AB  - BACKGROUND: Displaced intracapsular fractures may be treated by either reduction
      and internal fixation which preserves the femoral head, or by replacement of the
      femoral head with an arthroplasty. OBJECTIVES: To review all randomised trials
      that have compared internal fixation and arthroplasty. SEARCH STRATEGY: We
      searched the Cochrane Musculoskeletal Injuries Group specialised register
      (January 2002), MEDLINE (1966 to January 2002), EMBASE (1988 to 2002, Week 2),
      Current Contents (1993 to 2002, Week 4), PREMEDLINE (January 2002) and selected
      orthopaedic journals and conference proceedings, and reference lists of relevant
      articles. We contacted trialists where possible. SELECTION CRITERIA: All
      randomised and quasi-randomised trials comparing internal fixation with
      arthroplasty for intracapsular hip fractures in adults. DATA COLLECTION AND
      ANALYSIS: Trial quality was assessed by use of a 10 item scale. Data from the
      majority of trials were independently extracted by three reviewers with the
      remaining extracted by two. Additional information was sought from trialists.
      After grouping into three broad categories, comparable groups of trials were
      subgrouped and where appropriate, data were pooled using the fixed effects model.
      MAIN RESULTS: Thirteen trials involving 2091 patients were included. Internal
      fixation had a reduced length of surgery, operative blood loss, need for blood
      transfusion and risk of deep wound infection. Arthroplasty had a lower re
      operation rate in comparison with fixation. No definite differences for hospital
      stay, mortality, degree of residual pain, regain of mobility or regain of same
      residential state were found. REVIEWER'S CONCLUSIONS: Internal fixation is
      associated with less initial operative trauma but has an increased risk of re
      operation on the hip. Definite conclusions cannot be made for differences in pain
      and residual disability between the two groups. Future studies should concentrate
      on better reporting of final outcome measures and there is still a need for
      studies to define which patient groups are better served by the different
      treatment methods.

PMID- 12804414
TI  - Adrenergic drugs for urinary incontinence in adults.
AB  - BACKGROUND: Adrenergic drugs have been used for the treatment of urinary
      incontinence. However, they have generally been considered to be ineffective or
      to have side effects which may limit their clinical use. OBJECTIVES: To determine
      the effectiveness of adrenergic agonists in the treatment of urinary incontinence
      in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials
      register (January 2002) and the reference lists of relevant articles. Date of the
      most recent searches: January 2002. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials which include an adrenergic agonist drug in at least
      one arm for adults with urinary incontinence. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed eligibility, trial quality and extracted data.
      Data were processed as described in the Cochrane Collaboration Handbook. MAIN
      RESULTS: Fifteen randomised trials were identified, which included 832 women, of
      whom 506 received an adrenergic drug (phenylpropanolamine in 11 trials, Midodrine
      in two and Clenbuterol in another two). Of these, six were crossover trials. No
      trials included men. The limited evidence suggested that an adrenergic agonist
      drug is better than placebo in reducing number of pad changes and incontinence
      episodes, as well as improvement in subjective symptoms. The drugs also appeared
      to be better than pelvic floor muscle training in two small trials, possibly
      reflecting relative acceptability of the treatments to women but perhaps due to
      differential withdrawal of women from the trial groups. There was not enough
      evidence to evaluate the use of higher compared to lower doses of adrenergic
      agonists nor the relative merits of an adrenergic agonist drug compared with
      oestrogen, whether used alone or in combination. REVIEWER'S CONCLUSIONS: There
      was weak evidence to suggest that use of an adrenergic agonist is better than
      placebo treatment. There was not enough evidence to assess the effects of
      adrenergic agonists when compared to or combined with other treatments. Patients
      using adrenergic agonists may suffer from minor side effects, only occasionally
      leading them to stop treatment. Rare but serious side effects such as cardiac
      arrhythmias and hypertension have been reported, however.

PMID- 12804415
TI  - Physiotherapy treatment approaches for the recovery of postural control and lower
      limb function following stroke.
AB  - BACKGROUND: There are a number of different approaches to physiotherapy treatment
      following stroke. Central to these are approaches based on 'neurophysiological'
      principles, 'motor learning' principles and 'orthopaedic' principles. OBJECTIVES:
      To determine if there is a difference in the recovery of postural control and
      lower limb function in patients with stroke if physiotherapy treatment is based
      on orthopaedic or neurophysiological or motor learning principles, or on a
      mixture of these treatment principles. SEARCH STRATEGY: This review drew on the
      search strategy developed by the Stroke Group as a whole. Relevant trials were
      identified in the Stroke Group Trials Register of Controlled Trials which was
      last searched in May 2001. We also searched the Cochrane Controlled Trials
      Register (Cochrane Library, Issue 4 1999), MEDLINE (1966-1999), EMBASE (1980
      1999) and CINAHL (1982-1999) and contacted experts and researchers with an
      interest in stroke. SELECTION CRITERIA: Studies - randomised or quasi-randomised
      controlled trials. Participants - adults with a clinical diagnosis of stroke.
      Interventions - physiotherapy treatment approaches aimed at promoting the
      recovery of postural control and lower limb function. Outcomes - measures of
      disability, motor impairment or participation. DATA COLLECTION AND ANALYSIS: Two
      independent reviewers categorised the identified trials according to the
      inclusion/exclusion criteria, documented the methodological quality and extracted
      the data. MAIN RESULTS: Eleven trials were included in the review, three of which
      were included in two comparisons. Four trials compared a neurophysiological
      approach with another approach; four trials compared a motor learning approach
      with another approach; four studies compared a mixed approach with another
      approach; two trials reported comparisons of sub-groups of the same approach. A
      large number of heterogeneous outcome measures were used, limiting the comparison
      of trial results. No one type of approach had a significantly better outcome than
      any other type of approach. REVIEWER'S CONCLUSIONS: There is insufficient
      evidence to conclude that any one physiotherapy treatment approach is more
      effective than another in promoting the recovery of postural control or lower
      limb function.

PMID- 12804416
TI  - Branched-chain amino acids for hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy may be caused by a decreased plasma ratio of
      branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA
      may therefore have a beneficial effect on patients with hepatic encephalopathy.
      OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA for patients
      with hepatic encephalopathy. SEARCH STRATEGY: We identified trials through The
      Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue
      3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of
      bibliographies and journals, authors of trials, and pharmaceutical companies.
      SELECTION CRITERIA: Randomised trials comparing BCAA with any kind of control
      therapy for hepatic encephalopathy were included, regardless of blinding,
      language, or publication status. DATA COLLECTION AND ANALYSIS: Trial inclusion
      and data extraction were made independently by two reviewers. Our primary outcome
      was improvement of hepatic encephalopathy. Statistical heterogeneity was tested
      using random effects and fixed effect models. Binary outcomes are reported as
      risk ratios (RR) based on a random effects model. MAIN RESULTS: Eleven randomised
      trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or
      isonitrogenous control were included. The median number of patients in each trial
      was 55 (range 22 to 75). Follow-up after treatment was reported in four trials
      (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA
      significantly increased the number of patients improving from hepatic
      encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence
      interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of
      BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events
      (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that
      methodological quality had significant impact on the results. We found no
      evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials
      with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to
      1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to
      1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73,
      three trials). REVIEWER'S CONCLUSIONS: We did not find convincing evidence that
      BCAA had a significant beneficial effect on patients with hepatic encephalopathy.
      The trials performed in this field were small with short follow-up and most had
      low methodological quality.

PMID- 12804417
TI  - Initial management strategies for dyspepsia.
AB  - BACKGROUND: This review considers management strategies (combinations of initial
      investigation and empirical treatments) for dyspeptic patients. Dyspepsia was
      defined to include both epigastric pain and heartburn. OBJECTIVES: To determine
      the effectiveness, acceptability, and cost effectiveness of the following initial
      management strategies for patients presenting with dyspepsia (a) initial
      pharmacological therapy (including endoscopy for treatment failures) (b) early
      endoscopy (c) testing for Helicobacter pylori and endoscope only those positive
      (d) H.pylori eradication therapy with or without prior testing. SEARCH STRATEGY:
      Trials were located through electronic searches and extensive contact with
      trialists. SELECTION CRITERIA: All randomised controlled trials of dyspeptic
      patients presenting in primary care. DATA COLLECTION AND ANALYSIS: Data was
      collected on dyspeptic symptoms, quality of life and use of resources. MAIN
      RESULTS: Twenty papers reporting 23 comparisons were found. Trials comparing
      proton pump inhibitors (PPI) with antacids (two trials) and H2 receptor
      antagonists (three trials), early endoscopy with initial acid suppression (five
      trials), H.pylori 'test and scope' v usual management (three trials), H.pylori
      test and treat v. endoscopy (four trials), and test and treat v. acid suppression
      alone in H.pylori positive patients (two trials), were pooled. PPIs were
      significantly more effective than both H2RAs and antacids. Relative risks (RR)
      and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85).
      Results for other drug comparisons were either absent or inconclusive. Initial
      endoscopy was associated with a small reduction in the risk of recurrent
      dyspeptic symptoms compared with initial prescribing (RR 0.89 (0.77-1.02).
      H.pylori test and endoscopy increases costs in primary care, but does not improve
      symptoms. H.pylori test and eradicate may be as effective as endoscopy- based
      management and reduces costs, by decreasing the proportion of patients that are
      endoscoped. 'Test and treat' may be more effective than acid suppression alone,
      RR 0.59 (0.42-0.83). REVIEWER'S CONCLUSIONS: PPIs are effective in the treatment
      of dyspepsia in these trials which may not adequately exclude patients with
      gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is
      uncertain. Early investigation by endoscopy or H.pylori testing may benefit some
      patients with dyspepsia. The review will be updated in 2004 with an individual
      patient data meta-analysis of the economic data, and a subgroup analysis by age
      and predominant dyspeptic symptom.

PMID- 12804418
TI  - Interventions for suspected placenta praevia.
AB  - BACKGROUND: Because placenta praevia is implanted unusually low in the uterus, it
      may cause major, and/or repeated, antepartum haemorrhage. The traditional policy
      of care of women with symptomatic placenta praevia includes prolonged stay in
      hospital and delivery by caesarean section. OBJECTIVES: To assess the impact of
      any clinical intervention applied specifically because of a perceived likelihood
      that a pregnant woman might have placenta praevia. SEARCH STRATEGY: A
      comprehensive electronic search was performed to identify relevant literature.
      Searched databases included the Trials Register maintained by the Cochrane
      Pregnancy and Childbirth Group (August 2002), and the Cochrane Controlled Trials
      Register (The Cochrane Library, Issue 2, 2002). SELECTION CRITERIA: Any
      controlled clinical trial that has assessed the impact of an intervention in
      women diagnosed as having, or being likely to have, placenta praevia. DATA
      COLLECTION AND ANALYSIS: Data were extracted, unblinded, by the author without
      consideration of results. MAIN RESULTS: Three trials were included, involving a
      total of 114 women. Both tested interventions (home versus hospitalisation and
      cervical cerclage versus no cerclage) were associated with reduced lengths of
      stay in hospital antenatally: weighted mean difference (WMD) respectively -18.50
      days (95% confidence interval (CI) -26.83 to -10.17), -4.80 days (95% CI -6.37 to
      -3.23). Otherwise, there was little evidence of any clear advantage or
      disadvantage to a policy of home versus hospital care. The one woman who had a
      haemorrhage severe enough to require immediate transfusion and delivery was in
      the home care group. Cervical cerclage may reduce the risk of delivery before 34
      weeks: relative risk (RR) 0.45 (95% CI 0.23 to 0.87), or the birth of a baby
      weighing less than two kilograms RR 0.34 (0.14 to 0.83) or having a low five
      minute Apgar score RR 0.19 (0.04 to 1.00). In general, these possible benefits
      were more evident in the trial of lower methodological quality. REVIEWER'S
      CONCLUSIONS: There are insufficient data from trials to recommend any change in
      clinical practice. Available data should, however, encourage further work to
      address the safety of more conservative policies of hospitalisation for women
      with suspected placenta praevia, and the possible value of insertion of a
      cervical suture.

PMID- 12804419
TI  - Alpha2 adrenergic agonists for the management of opioid withdrawal.
AB  - BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free
      treatment. It may also represent the end point of long-term treatment such as
      methadone maintenance. The availability of managed withdrawal is essential to an
      effective treatment system. OBJECTIVES: To assess the effectiveness of
      interventions involving the use of alpha2 adrenergic agonists (clonidine,
      lofexidine, guanfacine) to manage the acute phase of opioid withdrawal. SEARCH
      STRATEGY: Multiple electronic databases (including MEDLINE, EMBASE, PsycINFO,
      Australian Medical Index, Cochrane Clinical Trials Register) were systematically
      searched. Reference lists of retrieved studies, reviews and conference abstracts
      were handsearched and relevant pharmaceutical companies contacted. SELECTION
      CRITERIA: Controlled trials comparing alpha2 adrenergic agonists with reducing
      doses of methadone, symptomatic medications or placebo, or comparing different
      alpha2 adrenergic agonists to modify the signs and symptoms of withdrawal in
      participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS:
      One reviewer assessed studies for inclusion and undertook data extraction.
      Inclusion decisions and the overall process were confirmed by consultation
      between all four reviewers. MAIN RESULTS: Twenty-two studies, involving 1691
      participants, were included. Eighteen were randomised controlled trials; for the
      remaining studies allocation was by participant choice in one, another used
      alternate allocation and in two the method of allocation was unclear. Eleven
      studies compared a treatment regime based on an alpha2 adrenergic agonist with
      one based on reducing doses of methadone. Diversity in study design, assessment
      and reporting of outcomes limited the extent of quantitative analysis. For the
      comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone,
      there were insufficient data for statistical analysis, but withdrawal intensity
      appears similar to, or marginally greater with alpha2 adrenergic agonists, while
      signs and symptoms of withdrawal occur and resolve earlier in treatment.
      Participants stay in treatment longer with methadone. No significant difference
      was detected in rates of completion of withdrawal with adrenergic agonists
      compared to reducing doses of methadone, or clonidine compared to lofexidine.
      Clonidine is associated with more adverse effects (low blood pressure, dizziness,
      dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not
      reduce blood pressure to the same extent as clonidine, but is otherwise similar
      to clonidine. REVIEWER'S CONCLUSIONS: No significant difference in efficacy was
      detected for treatment regimes based on the alpha2 adrenergic agonists clonidine
      and lofexidine, and those based on reducing doses of methadone over a period of
      around 10 days, for the management of withdrawal from heroin or methadone.
      Participants stay in treatment longer with methadone regimes and experience less
      adverse effects. The lower incidence of hypotension makes lofexidine more suited
      to use in outpatient settings than clonidine. There are insufficient data
      available to support a conclusion on the efficacy of other alpha2 adrenergic
      agonists.

PMID- 12804420
TI  - Photodynamic therapy for neovascular age-related macular degeneration.
AB  - BACKGROUND: In neovascular age-related macular degeneration, new vessels grow
      under the retina, distorting vision and leading to scarring. This is further
      exacerbated if the blood vessels leak. Photodynamic therapy, originally used in
      cancer treatment, has been investigated as a way to treat the neovascular
      membranes without affecting the retina. OBJECTIVES: The aim of this review is to
      examine the effects of photodynamic therapy in the treatment of neovascular age
      related macular degeneration. SEARCH STRATEGY: We searched for trials in the
      Cochrane Central Register of Controlled Trials - CENTRAL (which includes the
      Cochrane Eyes and Vision Group trials register) on the Cochrane Library (Issue 4
      2002), MEDLINE (1966 to November 2002) and EMBASE (1980 to November 2002). We
      used the Science Citation Index to search for reports that cited relevant study
      reports. We contacted experts in the field and we searched the reference lists of
      relevant studies for further trial reports. SELECTION CRITERIA: We included
      randomised trials of photodynamic therapy in people with choroidal
      neovascularisation due to age-related macular degeneration. DATA COLLECTION AND
      ANALYSIS: Two reviewers extracted the data independently. Relative risks were
      combined using a fixed effect model after testing for heterogeneity using a chi
      square test. MAIN RESULTS: Two published trials were identified that randomised
      948 participants to verteporfin therapy compared to 5% dextrose in water. Both
      trials were performed by the same investigators using largely the same clinical
      centres and funded by manufacturers of verteporfin. Outcome data were available
      at 12 and 24 months after the first treatment. Participants received on average
      five treatments over two years. The relative risk of losing three or more lines
      of visual acuity at 24 months comparing the intervention with the control group
      was 0.77 (95% confidence interval 0.69 to 0.87). The relative risk of losing six
      or more lines of visual acuity at 24 months comparing the intervention with the
      control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12
      months were similar to those at 24 months. REVIEWER'S CONCLUSIONS: Photodynamic
      therapy in people with choroidal neovascularisation due to age-related macular
      degeneration is effective in preventing visual loss. Outcomes and potential
      adverse effects of this treatment should be monitored closely. Further
      independent trials of Verteporfin are required to establish that the effects seen
      in this study are consistent and to determine important questions not yet
      addressed, particularly relating to quality of life and cost.

PMID- 12804421
TI  - Biphasic versus monophasic oral contraceptives for contraception.
AB  - BACKGROUND: Side effects caused by oral contraceptives discourage compliance with
      and continuation of oral contraceptives. Three approaches have been used to
      decrease these adverse effects: reduction of steroid dose, development of new
      steroids, and new formulas and schedules of administration. The third strategy
      led to the biphasic oral contraceptive pill. OBJECTIVES: To compare biphasic with
      monophasic oral contraceptives in terms of efficacy, cycle control, and
      discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic
      oral contraceptives are less effective than monophasic oral contraceptives in
      preventing pregnancy, and (b) biphasic oral contraceptives cause more side
      effects, give poorer cycle control, and have lower continuation rates. SEARCH
      STRATEGY: We searched the computerized databases MEDLINE, EMBASE, Popline and the
      Cochrane Controlled Trials Register (CCTR). In addition, we searched the
      reference lists of all potentially relevant articles and book chapters. We also
      contacted the authors of relevant studies and pharmaceutical companies in Europe
      and the USA. SELECTION CRITERIA: We included randomized controlled trials
      comparing any biphasic with any monophasic oral contraceptive when used to
      prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found
      during the various literature searches for possible inclusion and assessed their
      methodology using Cochrane guidelines. We contacted the authors of all studies
      that were included and of possibly randomized studies for supplemental
      information about methodology and outcome. We entered the data in RevMan 3.1,
      imported the data into RevMan 4.1, and calculated Peto odds ratios for the
      incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study
      discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only one trial of
      limited quality compared a biphasic and monophasic preparation. Percival-Smith et
      al. (1990) examined 533 user cycles of a biphasic pill (500 mcg norethindrone/35
      mcg ethinyl estradiol for 10 days, followed by 1000 mcg norethindrone/35 mcg
      ethinyl estradiol for 11 days; Ortho 10/11) and 481 user cycles of a monophasic
      contraceptive pill (1500 norethindrone acetate mcg/30 mcg ethinyl estradiol
      daily; Loestrin). The study found no significant differences in intermenstrual
      bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding
      between the biphasic and monophasic oral contraceptive pills. REVIEWER'S
      CONCLUSIONS: Conclusions are limited by the identification of only one trial, the
      methodological shortcomings of that trial, and the absence of data on accidental
      pregnancies. However, the trial found no important differences in bleeding
      patterns between the biphasic and monophasic preparations studied. Since no clear
      rationale exists for biphasic pills and since extensive evidence is available for
      monophasic pills, the latter are preferred.

PMID- 12804422
TI  - Low level laser therapy (Classes I, II and III) for treating osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) affects a large proportion of the population. Low
      Level Laser Therapy (LLLT) is a light source that generates extremely pure light,
      of a single wavelength. The effect is not thermal, but rather related to
      photochemical reactions in the cells. LLLT was introduced as an alternative non
      invasive treatment for OA about 10 years ago, but its effectiveness is still
      controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment
      of OA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Musculoskeletal
      registry, the registry of the Rehabilitation and Related Therapies field and the
      Cochrane Controlled Trials Register up to December 31, 2002. SELECTION CRITERIA:
      Following an a priori protocol, only controlled clinical trials of LLLT for the
      treatment of patients with a clinical diagnosis of OA were eligible. Abstracts
      were excluded unless further data could be obtained from the authors. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected trials and
      abstracted data using predetermined forms. Heterogeneity was tested with
      Cochran's Q test. A fixed effects model was used throughout for continuous
      variables, except where heterogeneity existed, in which case, a random effects
      model was used. Results were analyzed as weighted mean differences (WMD) with 95%
      confidence intervals (CI), where the difference between the treated and control
      groups was weighted by the inverse of the variance. Standardized mean differences
      (SMD) were calculated by dividing the difference between treated and control by
      the baseline variance. SMD were used when different scales were used to measure
      the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds
      ratios. MAIN RESULTS: Five trials were included, with 112 patients randomized to
      laser, 85 patients to placebo laser. Treatment duration ranged from 4 to 10
      weeks. Pain was assessed by four trials. The pooled estimate (random effects) of
      three trials showed no statistically different effect on pain measured using a
      scale (SMD: -0.2, 95% CI: -1.0, +0.6), but there was statistically significant
      heterogeneity (p>0,05). Two of the trials showed no effect and one demonstrated
      very beneficial effects with laser. In another trial, with no scale-based pain
      outcome, significantly more patients reported pain relief (yes/no) with laser
      with an odds ratio of 0.05, (95% CI: 0.0 to 1.56). Other outcomes of joint
      tenderness, joint mobility and strength were not significant. REVIEWER'S
      CONCLUSIONS: For OA, the results are conflicting in different studies and may
      depend on the method of application and other features of the LLLT application.
      Clinicians and researchers should consistently report the characteristics of the
      LLLT device and the application techniques used. New trials on LLLT should make
      use of standardized, validated outcomes. Despite some positive findings, this
      meta-analysis lacked data on how LLLT effectiveness is affected by four important
      factors: wavelength, treatment duration of LLLT, dosage and site of application
      over nerves instead of joints. There is clearly a need to investigate the effects
      of these factors on LLLT effectiveness for OA in randomized controlled clinical
      trials.

PMID- 12804423
TI  - Inhaled versus systemic corticosteroids for the treatment of chronic lung disease
      in ventilated very low birth weight preterm infants.
AB  - BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among
      very low birth weight infants despite the use of antenatal steroids and postnatal
      surfactant therapy to decrease the incidence and severity of respiratory distress
      syndrome. Corticosteroids have been widely used to treat or prevent CLD due to
      their anti-inflammatory properties. However, the use of systemic steroids has
      been associated with serious short and long term adverse effects. Administration
      of corticosteroids topically through the respiratory tract might result in
      beneficial effects on the pulmonary system with fewer undesirable systemic side
      effects. OBJECTIVES: To compare the effectiveness of inhaled versus systemic
      corticosteroids administered to ventilator dependent preterm neonates with birth
      weight </= 1500 grams or gestational age </= 32 weeks after two weeks of life for
      the treatment of evolving CLD. SEARCH STRATEGY: Randomized and quasi-randomized
      trials were identified by searching the Cochrane Controlled Trials Register (The
      Cochrane Library, Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1980 -
      September 2002), CINAHL (1982 - September 2002), reference lists of published
      trials and abstracts published in Pediatric Research (1990 - April 2002) from the
      Society for Pediatric Research/Pediatric Academic Societies' Annual Meetings.
      SELECTION CRITERIA: Randomized or quasi-randomized trials comparing inhaled
      versus systemic corticosteroid therapy (irrespective of the dose and duration of
      therapy) starting after the first two weeks of life in ventilator dependent very
      low birth weight preterm neonates. DATA COLLECTION AND ANALYSIS: Data were
      extracted regarding clinical outcomes including CLD at 28 days or 36 weeks
      corrected gestational age (CGA), mortality, combined outcome of death or CLD at
      28 days or 36 weeks CGA, other pulmonary outcomes and adverse effects. All data
      were analyzed using RevMan 4.1. When appropriate, meta-analysis was performed
      using relative risk (RR), risk difference (RD), and weighted mean difference
      (WMD) along with their 95% confidence intervals (CI). If RD was statistically
      significant, number needed to treat (NNT) was calculated. MAIN RESULTS: Five
      trials comparing inhaled versus systemic corticosteroids in the treatment of CLD
      were identified. Two trials were excluded as both included non ventilator
      dependent patients. One trial is awaiting assessment and clarification of
      published data. Two trials qualified for inclusion in this review. Halliday et al
      (Halliday 2001a) randomized infants < 72 hours, while Suchomski et al (Suchomski
      2002) randomized at 12-21 days. Although the steroids were commenced after the
      first 2 weeks of life in both the trials, the outcomes were measured over
      different time periods, from the age at randomization in each trial, making it
      inappropriate to combine results. In neither trial was there a statistically
      significant difference between the groups in the incidence of CLD at 36 weeks CGA
      amongst all randomized infants. The estimates for the trial by Halliday et al
      (Halliday 2001a) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15);
      number of infants (n) = 292 and for the trial by Suchomski et al (Suchomski 2002)
      RR 0.90 (95% CI 0.79, 1.02), RD -0.10 (95% CI -0.22, 0.02; n = 78 ). There were
      no statistically significant differences between the groups in either trial for
      oxygen dependency at 28 days, death by 28 days or 36 weeks, the combined outcome
      of death or CLD by 28 days or 36 weeks CGA, duration of intubation, duration of
      oxygen dependence, or adverse effects. Information on the long term
      neurodevelopmental outcomes was not available. REVIEWER'S CONCLUSIONS: This
      review found no evidence that inhaled corticosteroids confer net advantages over
      systemic corticosteroids in the management of ventilator dependent preterm
      infants. Neither inhaled steroids, nor systemic steroids, can be recommended as
      standard treatment for ventilated preterm infants. There was no evidence of
      difference in effectiveness or side-effect profiles for inhaled versus systemic
      steroids. A better delivery system guaranteeing selective delivery of inhaled
      steroids to the alveoli might result in beneficial clinical effects without
      increasing side-effects. To resolve this issue, studies are needed to identify
      the risk/benefit ratio of different delivery techniques and dosing schedules for
      the administration of these medications. The long term effects of inhaled
      steroids, with particular attention to neurodevelopmental outcome, should be
      addressed in future studies.

PMID- 12804424
TI  - Drugs for preventing lung cancer in healthy people.
AB  - BACKGROUND: Some studies have suggested a protective effect of antioxidant
      nutrients on lung cancer. Observational epidemiological studies suggest an
      association between higher dietary levels of fruits and vegetables containing
      beta carotene and a lower risk of lung cancer. OBJECTIVES: To determine whether
      vitamins, minerals and other potential agents, alone or in combination, reduce
      incidence and mortality from lung cancer in healthy people. SEARCH STRATEGY: The
      electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the
      Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies
      were searched. In addition authors of included studies were contacted to identify
      potentially eligible published and unpublished trials. SELECTION CRITERIA:
      Included studies were randomised controlled clinical trials comparing different
      supplements or comparing supplements with placebo, administered to healthy people
      with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Three
      reviewers independently selected the trials to be included in the review and
      assessed the methodological quality of each trial, and two extracted data using a
      standardised form. For each study, relative risk and 95% confidence limits were
      calculated for dichotomous outcomes. MAIN RESULTS: Four studies were eligible for
      inclusion. All were population based trials, including a total of 109,394
      participants. Two studies included smokers, one included workers exposed to
      asbestos and two studies were carried out in health professionals. A group of
      participants with no known risk factors for lung cancer was included in the study
      sample of two trials. Beta-carotene was evaluated in all trials, alone or
      combination with alpha-tocopherol or retinol, and one study tested alpha
      tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up
      was from two to five years. All trials had a placebo group. For people with risk
      factors for lung cancer no reduction in lung cancer incidence or mortality was
      found in those taking vitamins alone compared with placebo (incidence of lung
      cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73
      1.19). For people with no known risk factors of lung cancer, none of the vitamins
      or their combinations appeared to have any effect. Combined data from three
      studies showed a non-statistically significant increased risk of lung cancer
      incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28)
      for beta-carotene alone at pharmacological doses in groups with risk factors for
      lung cancer. When beta-carotene was combined with retinol, data from a single
      study showed that there was a statistically significant, increased risk of lung
      cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29
      2.38) in people with risk factors for lung cancer who took both vitamins compared
      with those who took placebo. Data from also from one study showed that the
      combination of beta-carotene with alpha-tocopherol in people with risk factors
      for lung cancer was associated with a non-statistically significant increased
      risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15,
      95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality
      or all-cause mortality. REVIEWER'S CONCLUSIONS: There is currently no evidence to
      support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol,
      alone or in combination, to prevent lung cancer. A harmful effect was found for
      beta-carotene with retinol at pharmacological doses in people with risk factors
      for lung cancer (smoking and/or occupational exposure to asbestos). More research
      from larger trials and with longer follow-up is needed to analyse the
      effectiveness of other supplements.

PMID- 12804425
TI  - Methylxanthines for exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Most international guidelines currently recommend methylxanthines
      (e.g., theophylline, aminophylline) for severe exacerbations of chronic
      obstructive pulmonary disease (COPD), yet clinical trials underlying this
      recommendation have been small and underpowered. OBJECTIVES: To determine the
      benefit of methylxanthines compared to placebo for COPD exacerbations. SEARCH
      STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane
      Airways Review Group COPD Register, a compilation of systematic searches of
      CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory
      journals. Primary authors and content experts were contacted to identify eligible
      studies. Bibliographies from included studies and reviews were searched.
      SELECTION CRITERIA: Included studies were limited to RCTs of patients presenting
      with acute COPD exacerbations, treated with methylxanthines (oral or intravenous)
      or placebo plus standard care. Two reviewers independently selected articles for
      inclusion and assessed methodological quality. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently extracted data. Missing data were obtained from authors
      or calculated from other data presented in the paper. The data were analysed
      using the Cochrane Review Manager 4.1. Studies were pooled to yield weighted mean
      differences (WMD), standardised mean difference (SMD) or odds ratios (OR) and
      reported using 95% confidence intervals (95%CI). MAIN RESULTS: From 29 identified
      references, 4 RCTs met inclusion criteria (169 patients). Mean change in forced
      expiratory volume in one second (FEV1) at 2 hours was similar in methylxanthine
      and placebo groups. Data on clinical outcomes were sparse. Trends toward
      improvements in hospitalisation and length-of-stay were offset by a trend toward
      more relapses at one week. Changes in symptom scores were not significant.
      Methylxanthines caused more nausea and vomiting than placebo (OR: 4.6; 95% CI:
      1.7 to 12.6) and trended toward more frequent tremor, palpitations, and
      arrhythmias. REVIEWER'S CONCLUSIONS: Given current evidence, methylxanthines
      should not be used for COPD exacerbations. Possible beneficial effects in lung
      function and clinical endpoints were modest and inconsistent, whereas adverse
      effects were significantly increased. More selective agents, tested in larger
      randomised trials, are necessary if methylxanthines are to have any role in the
      treatment of COPD exacerbations.

PMID- 12804426
TI  - Oxatomide for stable asthma in adults and children.
AB  - BACKGROUND: Oxatomide is a histamine H1-receptor antagonist. As an oral agent,
      oxatomide may be useful in managing asthma. Some guidelines recommend oxatomide
      for long-term prophylaxis of asthma in children. There is no clear evidence
      whether children or adults with asthma benefit from oxatomide. OBJECTIVES: To
      determine whether oxatomide alone, or in combination with other interventions,
      results in better disease control in people with asthma. SEARCH STRATEGY: The
      Collaborative Airway Group register and Collaborations trial register CENTRAL
      were searched using terms: oxatomide* OR Celtect OR Pinset OR KW-4354 OR Tincet.
      Reference lists of all relevant trials or review articles were checked. Enquiries
      were made of authors of included studies and relevant pharmaceutical companies. A
      search of 'Igaku Chuo Zasshi' and 'J-Medicine' were made using the following
      terms: oxatomide (also in Japanese) or Celtect (also in Japanese) or KW-4354.
      SELECTION CRITERIA: Studies were randomised, placebo-controlled trials and the
      interventions were oxatomide or matched placebo given alone or in combination
      with other asthma-medication for at least 4 weeks. DATA COLLECTION AND ANALYSIS:
      Four independent reviewers performed assessments of methodological quality and
      extracted relevant data. MAIN RESULTS: Six studies are included in this review.
      Three studies were mainly conducted in adults, two were conducted in older
      children (5-16 years) and one in infants (18-25 months). Trial duration was 4 to
      52 weeks. Doses of oxatomide varied between studies, ranging from 1 mg/kg/day for
      infants to 180 mg/day for adults. Only data on adverse events was suitable for
      meta-analysis. Although PEF did not change significantly in any of the studies,
      the FVC and FEV1 improved significantly in two. There was no uniform change in
      symptom scores. There was no significant difference between oxatomide and placebo
      treatment in use of inhaled corticosteroid or bronchodilator. Two studies showed
      significant improvement with oxatomide as judged subjectively by physicians.
      Adverse events, analysed using data from 4 parallel and one cross over study,
      showed oxatomide to be associated with a significantly higher risk of any adverse
      event (OR: 2.97, 95%CI: 1.69 to 5.22) and drowsiness (OR: 5.22,95%CI: 2.53 to
      10.74). REVIEWER'S CONCLUSIONS: There is no evidence to show that oxatomide has a
      significant effect on the control of stable asthma. Some studies reported
      significant benefits in subjective parameters. There was improvement in some lung
      function outcomes reported, but this were not consistent across measures or
      studies and may represent reporting bias. Adverse events, including drowsiness,
      were significantly greater with oxatomide than placebo.

PMID- 12804427
TI  - Multidisciplinary biopsychosocial rehabilitation for subacute low back pain among
      working age adults.
AB  - BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely
      applied for chronic low back pain patients. The biopsychosocial approach can also
      prevent chronicity, by providing rehabilitation for patients who still have pain
      past the initial acute phase. Nevertheless, multidisciplinary treatment
      programmes are often laborious and long processes and require good collaboration
      between the patient, the rehabilitation team and the work place. By using
      workplace visits and developing close relationships with occupational health care
      providers, one might expect patients' working ability to improve. OBJECTIVES: The
      objective of this systematic review was to determine the effectiveness of
      multidisciplinary rehabilitation for subacute low back pain among working age
      adults. SEARCH STRATEGY: The reviewed studies for this review were electronically
      identified from MEDLINE, EMBASE, PsycLIT, CENTRAL, Medic, the Science Citation
      Index, reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for the broader area of musculoskeletal
      disorders. Trials on subacute low back pain were separated afterwards. The
      literature search was last updated in November 2002 in EMBASE and MEDLINE.
      SELECTION CRITERIA: From all references identified in our original search, we
      selected randomised controlled trials (RCTs) and non-randomised controlled
      clinical trials (CCTs). Trials had to assess the effectiveness of
      multidisciplinary rehabilitation for working age patients suffering from subacute
      low back pain (more than four weeks but less than three months). The
      rehabilitation program was required to be multidisciplinary, i.e., it had to
      consist of a physician's consultation plus either a psychological, social or
      vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS:
      Four reviewers blinded to journal and author selected trials that met the
      specified inclusion criteria. Two experts in the field of rehabilitation
      evaluated the clinical relevance and applicability of the findings of the
      selected studies for actual clinical use. Two other reviewers blinded to journal
      and author extracted the data and assessed the main results and the
      methodological quality of the studies, using standardized forms. Finally, a
      qualitative analysis was performed to evaluate the level of scientific evidence
      for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After
      screening 1808 abstracts, and the references of 65 reviews, we found only two
      relevant studies that satisfied our criteria on subacute low back pain. No more
      studies were found during the updates. Both studies were considered to be
      methodologically low quality RCTs. The clinical relevance of included studies was
      sufficient. There was moderate scientific evidence showing that multidisciplinary
      rehabilitation, which includes a workplace visit or more comprehensive
      occupational health care intervention, helps patients to return to work faster,
      results in fewer sick leaves and alleviates subjective disability. REVIEWER'S
      CONCLUSIONS: We conclude that there is moderate evidence of positive
      effectiveness of multidisciplinary rehabilitation for subacute low back pain and
      that a workplace visit increases the effectiveness. But because this evidence is
      based on trials that had some methodological shortcomings, and several expensive
      multidisciplinary rehabilitation programmes are commonly used for
      uncomplicated/non-specific subacute low back problems, there is an obvious need
      for high quality trials in this field.

PMID- 12804428
TI  - Multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among
      working age adults.
AB  - BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs for neck
      and shoulder pain require substantial staff and financial resources. Despite
      questionable scientific evidence of their effectiveness, they are widely used.
      Neck and shoulder complaints are common among working age adults and they are
      often associated with physical work load and stress. Pain in the neck and
      shoulder area cause biopsychosocial difficulties for the patient, especially if
      disability due to pain is prolonged. To help patients with biopsychosocial
      problems, or to prevent their development, multidisciplinary biopsychosocial
      programs are used for rehabilitation for patients with neck and shoulder pain.
      Nevertheless, multidisciplinary treatment programmes are often laborious and
      rather long processes and require good collaboration between the patient, the
      rehabilitation team and the work place. OBJECTIVES: The objective of this
      systematic review was to determine the effectiveness of multidisciplinary
      biopsychosocial rehabilitation for neck and shoulder pain among working age
      adults. SEARCH STRATEGY: The reviewed studies for this review were electronically
      identified from MEDLINE, EMBASE, PsycLIT, CENTRAL, Medic, the Science Citation
      Index, reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for more broad area of musculoskeletal
      disorders. Trials on neck and shoulder pain were separated afterwards. The
      literature search was updated in November 2002 by electronically searching
      MEDLINE and EMBASE. SELECTION CRITERIA: From all references identified in our
      original search, we selected randomized controlled trials (RCTs) and non
      randomized controlled clinical trials (CCTs). Trials had to assess the
      effectiveness of biopsychosocial rehabilitation for working age adults suffering
      from neck and shoulder pain. The rehabilitation program was required to be
      multidisciplinary, i.e., it had to consist of a physician's consultation plus
      either a psychological, social or vocational intervention, or a combination of
      these. DATA COLLECTION AND ANALYSIS: Four reviewers blinded to journal and author
      selected the trials that met the specified inclusion criteria. Two experts in the
      field of rehabilitation evaluated the clinical relevance and applicability of the
      findings of the selected studies for actual clinical use. Two other reviewers
      blinded to journal and author extracted the data and assessed the main results
      and the methodological quality of the studies, using standardized forms. Finally,
      a qualitative analysis was performed to evaluate the level of scientific evidence
      for the effectiveness of multidisciplinary biopsychosocial rehabilitation. MAIN
      RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we
      found only two relevant studies that satisfied our criteria. No more studies were
      found for this update. One of the studies was considered to be a methodologically
      low quality RCT and the other one was a methodologically low quality CCT. The
      clinical relevance of included studies was satisfactory. There was limited
      scientific evidence for the effectiveness of multidisciplinary biopsychosocial
      rehabilitation for neck and shoulder pain. REVIEWER'S CONCLUSIONS: We conclude
      that there appears to be little scientific evidence for the effectiveness of
      multidisciplinary biopsychosocial rehabilitation compared with other
      rehabilitation facilities for neck and shoulder pain. Multidisciplinary
      rehabilitation is a commonly used intervention for chronic neck and shoulder
      complaints, therefore we see an urgent need for high quality trials in this
      field.

PMID- 12804429
TI  - Buprenorphine maintenance versus placebo or methadone maintenance for opioid
      dependence.
AB  - BACKGROUND: Buprenorphine has recently been reported to be an alternative to
      methadone and LAAM for maintenance treatment of opioid dependent individuals,
      differing results are reported concerning its relative effectiveness indicating
      the need for an integrative review. OBJECTIVES: To evaluate the effects of
      buprenorphine maintenance against placebo and methadone maintenance in retaining
      patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We
      searched the following databases up to 2001, inclusive: Cochrane Drugs and
      Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE,
      EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol
      and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug
      Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on
      Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network
      (ABN), and Library of Congress databases, available NIDA monographs and the
      College on Problems of Drug Dependence Inc. proceedings, the reference lists of
      all identified studies and published reviews and authors of identified RCT's were
      asked about any other published or unpublished relevant RCT. SELECTION CRITERIA:
      Randomised clinical trials of buprenorphine maintenance compared with either
      placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND
      ANALYSIS: Reviewers evaluated the papers separately and independently, rating
      methodological quality of concealment of allocation; data were extracted
      independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen
      studies met the inclusion criteria, all were randomised clinical trials, all but
      one were double-blind. The method of concealment of allocation was not clearly
      described in 11 of the studies, otherwise methodological quality was good.
      Buprenorphine given in flexible doses appeared statistically significantly less
      effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI:
      0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High
      dose buprenorphine does not retain more patients than low dose methadone, but may
      suppress heroin use better. There was no advantage for high dose buprenorphine
      over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose
      buprenorphine was inferior in suppression of heroin use. Buprenorphine was
      statistically significantly superior to placebo medication in retention of
      patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses
      (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88).
      However, only high and very high dose buprenorphine suppressed heroin use
      significantly above placebo. REVIEWER'S CONCLUSIONS: Buprenorphine is an
      effective intervention for use in the maintenance treatment of heroin dependence,
      but it is not more effective than methadone at adequate dosages.

PMID- 12804430
TI  - Methadone maintenance therapy versus no opioid replacement therapy for opioid
      dependence.
AB  - BACKGROUND: Methadone maintenance was the first widely used form of opioid
      replacement therapy developed to treat heroin dependence, and it remains the best
      researched treatment for this problem. Despite the widespread use of methadone in
      maintenance treatment for opioid dependence in many countries, it is a
      controversial treatment whose effectiveness has been disputed. OBJECTIVES: To
      evaluate the effects of methadone maintenance treatment (MMT) compared with
      treatments that did not involve opioid replacement therapy (i.e., detoxification,
      offer of drug-free rehabilitation, placebo medication, wait-list controls) for
      opioid dependence. SEARCH STRATEGY: We searched all the following databases up to
      2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled
      Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www.
      state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA)
      [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre
      for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au],
      Australian Bibliographic Network (ABN), and Library of Congress databases,
      available NIDA monographs and the College on Problems of Drug Dependence Inc.
      proceedings, the reference lists of all identified studies and published reviews;
      authors of identified RCTs were asked about other published or unpublished
      relevant RCTs. SELECTION CRITERIA: All randomised controlled clinical trials of
      methadone maintenance therapy compared with either placebo maintenance or other
      non-pharmacological therapy for the treatment of opioid dependence. DATA
      COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and
      independently, rating methodological quality of concealment of allocation, data
      were extracted independently for meta-analysis and double-entered. MAIN RESULTS:
      Six studies met the criteria for inclusion in this review, all were randomised
      clinical trials, two were double-blind. There were a total number of 954
      participants. The method of concealment of allocation was inadequate in one
      study, not clearly described in four studies, but adequate in a sixth study.
      Based on the meta-analysis, methadone appeared statistically significantly more
      effective than non-pharmacological approaches in retaining patient in treatment
      (3 RCTs, RR=3.05; 95%CI: 1.75-5.35) and in the suppression of heroin use (3 RCTs,
      RR=0.32; 95%CI: 0.23-0.44), but not statistically in criminal activity (3 RCTs,
      RR=0.39; 95%CI: 0.12-1.25). REVIEWER'S CONCLUSIONS: Methadone is an effective
      maintenance therapy intervention for the treatment of heroin dependence as it
      retains patients in treatment and decreases heroin use better than treatments
      that do not utilise opioid replacement therapy. It does not show a statistically
      significant superior effect on criminal activity.

PMID- 12804431
TI  - Intravenous immunoglobulin for myasthenia gravis.
AB  - BACKGROUND: Myasthenia gravis is an autoimmune disease. In up to 90 per cent of
      cases IgG autoantibodies to the nicotinic acetylcholine receptor are detectable
      which mediate the neuromuscular transmission disorder. As with other autoimmune
      diseases, patients would be expected to benefit from intravenous immunoglobulin.
      Case series and two randomised controlled trials suggest that intravenous
      immunoglobulin may be beneficial. OBJECTIVES: The objective of this review is to
      examine the efficacy of intravenous immunoglobulin for treating exacerbations of
      myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched
      the Cochrane Neuromuscular Disease Group trials register (21 July 2002) and
      MEDLINE (January 1966 to July 2002) using 'myasthenia gravis' and 'intravenous
      immunoglobulin' as the search terms. SELECTION CRITERIA: All randomised or quasi
      randomised trials in which intravenous immunoglobulin was compared with no
      treatment, placebo or plasma exchange, in people with myasthenia gravis who were
      diagnosed by an internationally accepted definition. DATA COLLECTION AND
      ANALYSIS: One author extracted the data and the two others checked these data and
      the source from which they were derived. For methodological reasons, no formal
      meta-analysis was performed. MAIN RESULTS: We identified four randomised
      controlled trials (147 participants in total), all investigating short-term
      benefit. In the first study of 87 people with myasthenia gravis exacerbation,
      comparing intravenous immunoglobulin and plasma exchange, there was no
      statistically significant difference between the efficacy of the two treatments
      after two weeks. In the second study 12 people with moderate or severe myasthenia
      gravis were treated in a cross-over design trial with intravenous immunoglobulin
      or plasma exchange: no statistically significant difference in the efficacy of
      the two treatments was found after four weeks. In the third study 15 people with
      mild or moderate myasthenia gravis received intravenous immunoglobulin or a
      placebo: no significant difference in efficacy of intravenous immunoglobulin or
      placebo was found six weeks after treatment. The last study, which included 33
      people with moderate exacerbations of myasthenia gravis, compared intravenous
      immunoglobulin and methylprednisolone and showed no statistically significant
      difference in the efficacy of the two treatments. REVIEWER'S CONCLUSIONS: One
      randomised controlled trial did not show a significant difference between
      intravenous immunoglobulin and plasma exchange for treatment of severe
      exacerbations of myasthenia gravis. There is no evidence from randomised
      controlled trials to determine whether intravenous immunoglobulin for moderate or
      severe myasthenia gravis improves functional outcome or has a sparing effect on
      steroid dosage, nor is there sufficient evidence to favour intravenous
      immunoglobulin over steroids in moderate exacerbations. Further randomised
      controlled trials are needed.

PMID- 12804432
TI  - Adhesives for fixed orthodontic brackets.
AB  - BACKGROUND: Bonding of orthodontic brackets to teeth is important to enable
      effective and efficient treatment with fixed appliances. The problem is bracket
      failure during treatment which increases operator chairside time and lengthens
      treatment time. A prolonged treatment is likely to increase the oral health risks
      of orthodontic treatment with fixed appliances one of which is irreversible
      enamel decalcification. OBJECTIVES: To evaluate the effectiveness of different
      orthodontic adhesives for bonding. SEARCH STRATEGY: Electronic databases: the
      Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE and EMBASE. Date of most recent searches:
      August 2002 (CENTRAL) (The Cochrane Library Issue 2, 2002). SELECTION CRITERIA:
      Trials were selected if they met the following criteria: randomised controlled
      trials (RCTs) and controlled clinical trials (CCTs) comparing two different
      adhesive groups. Participants were patients with fixed orthodontic appliances.
      The interventions were adhesives that bonded stainless steel brackets to all
      teeth except the molars. The primary outcome was debond or bracket failure. DATA
      COLLECTION AND ANALYSIS: Data were recorded on decalcification as a secondary
      outcome, if present. Information regarding methods, participants, interventions,
      outcome measures and results were extracted in duplicate by pairs of reviewers
      (Nicky Mandall (NM) and Rye Mattick (CRM); Declan Millett (DTM) and Joy Hickman
      (JH2)). Since the data were not presented in a form that was amenable to meta
      analysis, the results of the review are presented in narrative form only. MAIN
      RESULTS: Three trials satisfied the inclusion criteria. A chemical cured
      composite was compared with a light cure composite (one trial), a conventional
      glass ionomer cement (one trial) and a polyacid-modified resin composite
      (compomer) (one trial). The quality of the trial reports was generally poor.
      REVIEWER'S CONCLUSIONS: It is difficult to draw any conclusions from this review,
      however, suggestions are made for methods of improving future research involving
      orthodontic adhesives.

PMID- 12804433
TI  - Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.
AB  - BACKGROUND: Both chemotherapy and endocrine therapy can be used as treatments for
      metastatic breast cancer. OBJECTIVES: To review the evidence and determine
      whether chemotherapy or endocrine therapy has the most beneficial effect on
      treatment outcomes (survival, response rate, toxicity and quality of life).
      SEARCH STRATEGY: The specialised register maintained by the Editorial Base of the
      Cochrane Breast Cancer Group was searched on 16th September 2002 using the codes
      for "advanced breast cancer", "chemotherapy" and "endocrine therapy". Details of
      the search strategy applied by the Group to create the register, and the
      procedure used to code references, are described in the Group's module on the
      Cochrane Library. SELECTION CRITERIA: Randomised trials comparing the effects of
      chemotherapy alone with endocrine therapy alone on pre-specified endpoints in
      metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Data were collected from
      published trials. Hazard ratios were derived for survival analysis and a fixed
      effect model was used for meta-analysis. Response rates were analysed as
      dichotomous variables. Toxicity and quality of life data were extracted where
      present. MAIN RESULTS: The primary analysis of overall effect using hazard ratios
      derived from published survival curves involved six trials (692 women). There was
      no significant difference seen (HR=0.94, 95%CI 0.79-1.12, p=0.5). A test for
      heterogeneity was p=0.1. A pooled estimate of reported response rates in eight
      trials involving 817 women shows a significant advantage for chemotherapy over
      endocrine therapy with RR=1.25 (1.01-1.54, p=0.04). However the two largest
      trials showed trends in opposite directions, and a test for heterogeneity was
      p=0.0018. There was little information available on toxicity and quality of life.
      Six of the seven fully published trials commented on increased toxicity with
      chemotherapy, mentioning nausea, vomiting and alopecia. Three of the seven
      mentioned aspects of quality of life, with differing results. Only one trial
      formally measured quality of life, concluding that it was better with
      chemotherapy. REVIEWER'S CONCLUSIONS: In women with metastatic breast cancer and
      where hormone receptors are present, a policy of treating first with endocrine
      therapy rather than chemotherapy is recommended except in the presence of rapidly
      progressive disease.

PMID- 12804434
TI  - Progressive resistance strength training for physical disability in older people.
AB  - BACKGROUND: Muscle weakness in old age, is associated with physical disability
      and an increased risk of falls. Progressive resistance strength (PRT) training
      exercises (i.e. movements performed against a specific external force that is
      regularly increased during training) are designed to increase strength in older
      people. OBJECTIVES: To assess the effect of PRT on measures of physical
      disability, functional limitation and impairment in older people, and identify
      adverse events. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group specialized register (to August 2002), CENTRAL/CCTR (The Cochrane
      Library Issue 2, 2002), MEDLINE (1966 to February 1, 2002), EMBASE (1980 to
      February 1, 2002), CINAHL (1982 to February 1, 2002), Sports Discus (1948 to
      February 1, 2002), PEDro - The Physiotherapy Evidence Database (accessed February
      1, 2002) and Digital Dissertations (accessed February 1, 2002). We also searched
      reference lists of articles, reviewed conference abstracts and contacted authors.
      SELECTION CRITERIA: Randomised trials of PRT alone for older people (i.e. mean
      age of 60 or over) were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted data. Weighted mean
      differences (WMD) were obtained using fixed or random effect models as
      appropriate. When measures with different units were pooled, standardised mean
      differences (SMD) were calculated. Relative risks were calculated for dichotomous
      outcomes. MAIN RESULTS: Sixty-six trials with 3783 participants were included.
      Most studies were small and of poor quality. PRT had a large positive effect on
      strength (41 trials, 1955 participants), but there was statistical heterogeneity
      that was not explained by differences in study quality, participant
      characteristics or the exercise program. Some functional limitation measures
      showed modest improvements (i.e. gait speed, 14 trials, 798 participants, WMD
      0.07 m/s, 95% CI 0.04 to 0.09). However, there was no evidence that PRT had an
      effect on physical disability when activity measures or health related quality of
      life measures (HRQOL) were assessed (10 trials, 798 participants, SMD 0.01, 95%
      CI -0.14 to 0.16 ). Adverse events were poorly recorded, but musculoskeletal
      injuries were detected in most of the studies that prospectively defined and
      monitored these events. REVIEWER'S CONCLUSIONS: PRT appears to be an effective
      intervention to increase strength in older people and has a positive effect on
      some functional limitations. However, the effect of this intervention on more
      substantive outcomes such as measures of disability or HRQOL remains unclear. It
      is difficult to determine the balance of risks and benefits of PRT because
      adverse events have generally been poorly collected and recorded.

PMID- 12804435
TI  - Non-invasive ventilation for cystic fibrosis.
AB  - BACKGROUND: The use of non-invasive ventilation (NIV) has been proposed as a
      means to temporarily reverse or slow the progression of worsening respiratory
      failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus
      no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group trials register which comprises references
      identified from comprehensive electronic database searches, handsearching
      relevant journals and abstract books of conference proceedings. The reference
      lists of each trial were searched for additional publications that may contain
      other trials. Date of most recent search: January 2002. SELECTION CRITERIA:
      Relevant randomised controlled trials in which a form of pressure preset or
      volume preset NIV versus no NIV was used in people with acute or chronic
      respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trials for inclusion criteria, methodological quality and
      data extraction. MAIN RESULTS: Six trials were identified and four trials met the
      inclusion criteria with a total of 55 participants. All of these trials only
      evaluated single treatment sessions. Two trials (36 participants) evaluated the
      use of NIV for airway clearance compared with an alternative physiotherapy
      method. These trials showed that airway clearance may be easier and people with
      CF may prefer to use NIV for airway clearance. There was no evidence that NIV
      increases sputum expectoration or improves lung function. Two trials (19
      participants) evaluated the use of NIV for overnight ventilatory support. Of the
      primary outcomes examined in this review, only lung function was evaluated within
      the two trials. Due to the small numbers of participants and the differing
      statistical techniques used within the review and the primary trials, there were
      discrepancies in the results obtained by the RevMan analysis and the original
      trial analysis. No clear differences were found between NIV compared with either
      oxygen or room air. REVIEWER'S CONCLUSIONS: Non-invasive ventilation may be a
      useful adjunct to other airway clearance techniques, particularly in people with
      CF who have difficulty expectorating sputum. Non-invasive ventilation when used
      in addition to oxygen may improve gas exchange during sleep to a greater extent
      than oxygen therapy alone in moderate to severe disease. These benefits of NIV
      have only been demonstrated in single treatment sessions and its efficacy, safety
      and acceptability in the longer term are unknown. There is a need for long-term
      randomised controlled trials to determine the clinical effects of non-invasive
      ventilation in CF.

PMID- 12804436
TI  - Kangaroo mother care to reduce morbidity and mortality in low birthweight
      infants.
AB  - BACKGROUND: Kangaroo mother care (KMC), defined as skin-to-skin contact between a
      mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding,
      and early discharge from hospital, has been proposed as an alternative to
      conventional neonatal care for low birthweight (LBW) infants. OBJECTIVES: To
      determine whether there is evidence to support the use of KMC in LBW infants as
      an alternative to conventional care after the initial period of stabilization
      with conventional care. SEARCH STRATEGY: We used the standard search strategy of
      the Neonatal Review Group of the Cochrane Collaboration. MEDLINE, EMBASE, LILACS,
      POPLINE and CINAHL databases (to December 2002), and the Cochrane Controlled
      Trials Register (The Cochrane Library), were searched using the key words terms
      "kangaroo mother care" or "kangaroo care" or "kangaroo mother method" or "skin-to
      skin contact" and "infants" or "low birthweight infants". SELECTION CRITERIA:
      Randomized trials comparing KMC and conventional neonatal care in LBW infants.
      DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted
      independently by two reviewers. Statistical analysis was conducted using the
      standard Cochrane Collaboration methods. MAIN RESULTS: Three studies, involving
      1362 infants, were included. All the trials were conducted in developing
      countries. The studies were of moderate to poor methodological quality. The most
      common shortcomings were in the areas of blinding procedures for those who
      collected the outcomes measures, handling of drop outs, and completeness of
      follow-up. The great majority of results consist of results of a single trial.
      KMC was associated with the following reduced risks: nosocomial infection at 41
      weeks' corrected gestational age (relative risk 0.49, 95% confidence interval
      0.25 to 0.93), severe illness (relative risk 0.30, 95% confidence interval 0.14
      to 0.67), lower respiratory tract disease at 6 months follow-up (relative risk
      0.37, 95% confidence interval 0.15 to 0.89), not exclusively breastfeeding at
      discharge (relative risk 0.41, 95% confidence interval 0.25 to 0.68), and
      maternal dissatisfaction with method of care (relative risk 0.41, 95% confidence
      interval 0.22 to 0.75). KMC infants had gained more weight per day by discharge
      (weighted mean difference 3.6 g/day, 95% confidence interval 0.8 to 6.4). Scores
      on mother's sense of competence according to infant stay in hospital and
      admission to NICU were better in KMC than in control group (weighted mean
      differences 0.31 [95% confidence interval 0.13 to 0.50] and 0.28 [95% confidence
      interval 0.11 to 0.46], respectively). Scores on mother's perception of social
      support according to infant stay in NICU were worse in KMC group than in control
      group (weighted mean difference -0.18 (95% confidence interval -0.35 to -0.01).
      Psychomotor development at 12 months' corrected age was similar in the two
      groups. There was no evidence of a difference in infant mortality. However,
      serious concerns about the methodological quality of the included trials weaken
      credibility in these findings. REVIEWER'S CONCLUSIONS: Although KMC appears to
      reduce severe infant morbidity without any serious deleterious effect reported,
      there is still insufficient evidence to recommend its routine use in LBW infants.
      Well designed randomized controlled trials of this intervention are needed.

PMID- 12804437
TI  - Medical adjuvant treatment to increase patency of arteriovenous fistulae and
      grafts.
AB  - BACKGROUND: End Stage Renal Failure (ESRF) patients often require either the
      formation of an arteriovenous (A-V) fistula or an A-V interposition prosthetic
      shunt for haemodialysis. OBJECTIVES: To determine the effects of adjuvant drug
      treatment on the patency of fistulae and shunts in patients with ESRF undergoing
      haemodialysis by assessing the number of thrombotic episodes. SEARCH STRATEGY:
      Publications describing (or potentially describing), randomised controlled trials
      of medical adjuvant treatment of patients with ESRF on haemodialysis via A-V
      fistula or interposition prosthetic A-V shunt, were sought through electronic
      searches of the Cochrane Peripheral Vascular Diseases Specialised Trials Register
      (last searched October 2002), and the Cochrane Central Register of Controlled
      Trials (CENTRAL) database (last searched Issue 3, 2002). SELECTION CRITERIA:
      Randomised controlled trials of active drug versus placebo in patients with ESRF
      undergoing haemodialysis via an A-V fistula or prosthetic interposition A-V
      shunt. DATA COLLECTION AND ANALYSIS: Two reviewers (ADS, PAR), independently
      assessed trial quality and three (ADS, XE, PAR) extracted data. Information on
      adverse events was collected from the trials. The outcome measure analysed was
      the long term fistula, or shunt patency rate. MAIN RESULTS: The overall search
      identified three randomised controlled trials of aspirin versus placebo with a
      total number of 173 participants followed up to a maximum of 18 months. The
      aspirin dosage given was different in each of the trials (325 mg/once daily; 500
      mg/once daily; and 160 mg/once daily). The overall result of the meta-analysis
      favoured treatment with aspirin (Odds Ratio (OR) 0.42, 95% Confidence Interval
      (CI) 0.20 to 0.86). The overall p-value for the three studies was 0.02. Three
      ticlopidine (a platelet aggregation inhibitor) versus placebo trials were also
      identified with a total number of 312 participants. All patients were followed up
      for one month, and the dose of ticlopidine given was the same for all three
      studies (250 mg/twice daily). The overall result of the meta-analysis also
      favoured treatment. (OR = 0.47, 95% CI 0.26 to 0.85). P-value for overall effect
      was 0.01. One trial in a parallel group design examined the effect of
      dipyridamole versus placebo, and dipyridamole plus aspirin versus placebo, and
      followed up patients for eighteen months. The overall result favoured treatment
      (OR 0.29, 95% CI 0.06 to 1.40) and (OR 0.77, CI 0.19 to 3.19) respectively.
      REVIEWER'S CONCLUSIONS: The meta-analysis confirmed the beneficial effect of
      antiplatelet treatment as an adjuvant to increase the patency of A-V fistulae and
      shunts in the short term.

PMID- 12804438
TI  - Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in
      patients with chronic hepatitis B.
AB  - BACKGROUND: Chronic hepatitis B infection may cause liver cancer (hepatocellular
      carcinoma (HCC)). Alpha-fetoprotein (AFP) and liver ultrasonography (US) are used
      to screen these patients for HCC. It is uncertain whether screening is
      worthwhile. OBJECTIVES: To review randomized trials on screening for HCC with
      alpha-fetoprotein and/or liver ultrasonography among people with hepatitis B
      surface antigen (HBsAg) whether asymptomatic or with clinical liver disease.
      SEARCH STRATEGY: Relevant reports were searched from electronic databases until
      August 2002 (The Cochrane Hepato-Biliary Group Controlled Trials Register, The
      Cochrane Controlled Trials Register, MEDLINE, EMBASE, HealthStar, and the Chinese
      Medical Literature Electronic Databases, MedCyber) supplemented with manual
      searches on the bibliographies of papers found and communication to people
      familiar with chronic hepatitis B. SELECTION CRITERIA: Randomized trials on
      screening for liver cancer were included irrespective of language. Studies were
      excluded if the hepatitis B status was uncertain, if patients were not adequately
      followed, if the screening tests were not sensitive, widely-used ones, or if the
      test was used for diagnosis rather than screening for HCC. DATA COLLECTION AND
      ANALYSIS: We analyzed independently all the studies considered for inclusion. We
      wrote to the relevant authors for further information. Data were analyzed with
      Peto's odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Two
      trials met the selection criteria. One trial (n = 18,816) compared bi-annual AFP
      plus US screening with no screening for five years. No data on all-cause
      mortality were available. The two groups did not differ significantly regarding
      HCC mortality (OR 0.81; 95% CI 0.54 to 1.22). Number of patients with HCC was
      significantly increased in the screeened group (OR 1.37; 95% CI 1.00 to 1.88).
      Most HCCs in the screened group, but none in the control group, were at an early
      stage. The survival rate of patients with resected HCC in the screened group
      reached 52.7% after three and five years, but was 0% for those in the control
      group. The authors' estimated lead-time for HCC was 5.4 months, suggesting that
      screening prolonged the survival of HCC. Another trial (n = 1069) compared AFP
      plus US versus AFP screening, but could not decide which approach was superior
      due to the small sample size (number of detected HCC: OR 0.74; 95% CI 0.26 to
      2.12). REVIEWER'S CONCLUSIONS: There are not enough quality trials to support or
      refute screening of HBsAg-positive patients for HCC. It is possible that
      screening may be effective, but also that harm caused by screening/treatment may
      outweigh any gain. More and better-designed large randomized trials are required.

PMID- 12804439
TI  - Amantadine for fatigue in multiple sclerosis.
AB  - BACKGROUND: Fatigue is one of the most common and disabling symptoms of people
      with Multiple Sclerosis (MS). The effective management of fatigue has an
      important impact on the patient's functioning, abilities, and quality of life.
      Although a number of strategies have been devised for reducing fatigue, treatment
      recommendations are based on a limited amount of scientific evidence. Many
      textbooks report amantadine as a first-choice drug for MS-related fatigue because
      of published randomised controlled trials (RCTs) showing some benefit. We
      performed a systematic review in order to gather existing evidence, and
      contribute to the topic. OBJECTIVES: To determine the effectiveness and safety of
      amantadine in reducing fatigue in people with MS. SEARCH STRATEGY: RCTs of
      amantadine were identified using MEDLINE, EMBASE, bibliographies of relevant
      articles, personal communications, manual searches of relevant journals, and
      information from drug companies. SELECTION CRITERIA: Randomised, placebo or other
      drugs-controlled, double-blind trials of amantadine in MS people with fatigue.
      DATA COLLECTION AND ANALYSIS: Three reviewers selected studies for inclusion in
      the review and they extracted the data reported in the original articles. Missing
      and unclear data were requested by correspondence with the trial's principal
      investigator. A meta-analysis was not performed due to the inadequacy of
      available data, heterogeneity of outcome measures. MAIN RESULTS: Out of twelve
      pertinent publications, four trials met the criteria for inclusion in this
      review: one study was a parallel arms study, and 3 were crossover trials. The
      number of randomised participants ranged between 10 and 115, and a total of 236
      MS patients had been studied. Overall the quality of the studies considered was
      poor and all trials were open to bias. All studies reported small and inconstant
      improvements in fatigue, whereas the clinical relevance of these findings and the
      impact on patient's functioning and health related quality of life remains
      undetermined. The number of participants reporting side effects during amantadine
      therapy ranged from 10% to 57%, without significant differences between treatment
      and placebo. The side effects reported were generally mild, and discontinuation
      of the drug due to side effects occurred in less than 10% of the patients.
      REVIEWER'S CONCLUSIONS: Amantadine treatment is overall well tolerated, however
      its efficacy in reducing fatigue in people with MS is poorly documented and there
      is insufficient evidence to make recommendations to guide prescribing. It is
      advisable to (a) improve knowledge on the underlying mechanisms of MS-related
      fatigue; (b) achieve an agreement on accurate, reliable and responsive outcome
      measures of fatigue; (c) perform good quality RCTs.

PMID- 12804440
TI  - Propentofylline for dementia.
AB  - BACKGROUND: Propentofylline is a novel therapeutic agent for dementia that
      readily crosses the blood-brain barrier and acts by blocking the uptake of
      adenosine and inhibiting the enzyme phosphodiesterase. In vitro and in vivo its
      mechanism of action appears to be twofold; it inhibits the production of free
      radicals and reduces the activation of microglial cells. It therefore interacts
      with the inflammatory processes that are thought to contribute to dementia, and
      given its mechanism of action is a possible disease modifying agent rather than a
      purely symptomatic treatment. OBJECTIVES: To determine the clinical efficacy and
      safety of propentofylline for people with dementia. SEARCH STRATEGY: The trials
      were identified from a search of the Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group on 5 February 2003. Aventis, the
      manufacturing pharmaceutical company, was asked for data from unpublished studies
      but declined to enter into correspondence. SELECTION CRITERIA: Unconfounded
      double-blind randomized controlled trials of propentofylline compared with a
      placebo or another treatment group. DATA COLLECTION AND ANALYSIS: There were
      detailed reports of only four of the nine included studies. The efficacy of
      propentofylline was reviewed for undifferentiated dementia as there were not
      enough data to attempt a subgroup analysis for the types of dementia. MAIN
      RESULTS: The following statistically significant treatment effects in favour of
      propentofylline are reported. Cognition at 3, 6 and 12 months including MMSE at
      12 months. [MD 1.2, 95%CI 0.12 to 2.28, P=0.03] Severity of dementia at 3, 6 and
      12 months including CGI at 12 months [MD -0.21, 95%CI -0.39 to -0.03, P=0.03].
      Activities of Daily Living (NAB) at 6 and 12 months [MD -1.20, 95%CI -2.22 to 
      0.18, P=0.02]. Global Assessment (CGI) at 3 months [MD -0.48, 95% CI -0.75 to 
      0.21, P=0.0006], but not at later times. Tolerability There were minimal data on
      adverse effects and drop-outs. There were a statistically significant treatment
      effects in favour of placebo at 12 months, for the number of dropouts, [OR=1.43,
      95%CI 1.04 to 1.90, P=0.03]. REVIEWER'S CONCLUSIONS: There is limited evidence
      that propentofylline might benefit cognition, global function and activities of
      daily living of people with Alzheimer's disease and/or vascular dementia. The
      meta-analyses reported here are far from satisfactory as a summary of the
      efficacy of propentofylline, considering the unpublished information on another
      1200 patients in randomized trials that exists. Unfortunately Aventis has been
      unwilling to correspond with the authors, significantly limiting the scope of
      this review.

PMID- 12804441
TI  - Corticosteroids for hospitalised children with acute asthma.
AB  - BACKGROUND: Systemic corticosteroids are used routinely in the management of
      children with severe acute asthma. There is a lack of consensus regarding the
      agent, dose and route of corticosteroid administration. OBJECTIVES: To determine
      the benefit of systemic corticosteroids (oral, intravenous, or intramuscular)
      compared to placebo and inhaled steroids in acute paediatric asthma. SEARCH
      STRATEGY: All controlled trials were identified from the Cochrane Airways Review
      Group Register, hand searching of respiratory journals, reference lists and
      contacts with experts and pharmaceutical companies. SELECTION CRITERIA: Studies
      were included if they described a randomised controlled trial (RCT) involving
      children aged 1-18 years with severe acute asthma who received oral, inhaled,
      intravenous or intramuscular corticosteroids. Only studies in which patients
      required hospital admission were included. DATA COLLECTION AND ANALYSIS: Two
      reviewers using a standard form extracted all data. All data, numeric
      calculations and graphic extrapolations were independently confirmed. MAIN
      RESULTS: Seven trials were included with a total of 426 children studied (274
      with oral prednisone vs. placebo, 106 with intravenous steroids vs placebo and 46
      with nebulised budesonide vs prednisolone). A significant number of steroid
      treated children were discharged early after admission (>4 hours) with an OR of
      7.00 (95% CI: 2.98 to 16.45) and NNT of 3 (95%CI: 2 to 8). The length of stay was
      shorter in the steroid groups with a WMD of -8.75 hours (95% CI: -19.23 to 1.74).
      There were no significant differences between groups in pulmonary function or
      oxygen saturation measurements. Children treated with steroids in hospital were
      less likely to relapse within one to three months with OR 0.19 (95%CI: 0.07 to
      0.55) and NNT of 3 (95%CI: 2 to 7). The single small study that compared
      nebulised budesonide to oral prednisone failed to demonstrate equivalence or a
      difference between each therapy. REVIEWER'S CONCLUSIONS: Systemic corticosteroids
      produce some improvements for children admitted to hospital with acute asthma.
      The benefits may include earlier discharge and fewer relapses. Inhaled or
      nebulised corticosteroids cannot be recommended as equivalent to systemic
      steroids at this time. Further studies examining differing doses and routes of
      administration for corticosteroids will clarify the optimal therapy.

PMID- 12804442
TI  - Sublingual immunotherapy for allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is a common condition which, at its most severe,
      can significantly impair quality of life despite optimal treatment with
      antihistamines and topical nasal corticosteroids. Allergen injection
      immunotherapy significantly reduces symptoms and medication requirements in
      allergic rhinitis but its use is limited by the possibility of severe systemic
      reactions. There has therefore been considerable interest in alternative routes
      for delivery of allergen immunotherapy, particularly the sublingual route.
      OBJECTIVES: To evaluate the efficacy of sublingual immunotherapy (SLIT), compared
      with placebo, for reductions in symptoms and medication requirements. SEARCH
      STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (1966-2002), EMBASE
      (1974-2002) and Scisearch were searched, up to September 2002, using the terms
      (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual).
      SELECTION CRITERIA: All studies identified by the searches were assessed by the
      reviewers to identify randomised controlled trials involving participants with
      symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT
      or corresponding placebo. DATA COLLECTION AND ANALYSIS: Data from identified
      studies were abstracted onto a standard extraction sheet and subsequently entered
      into RevMan 4.1. Analysis was performed by the method of Standardised Mean
      Differences (SMD) using a random effects model. P values <0.05 were considered
      statistically significant. Subgroup analyses were performed according to the type
      of allergen administered, the age of participants and the duration of treatment.
      MAIN RESULTS: Twenty two trials involving 979 patients were included. There were
      6 trials of SLIT for House Dust Mite allergy, 5 for Grass Pollen, 5 for
      Parietaria, 2 for Olive and one each for, Ragweed, Cat, Tree and Cupressus. Four
      studies enrolled exclusively children. Seventeen studies administered the
      allergen by sublingual drops subsequently swallowed, 3 by drops subsequently spat
      out and 2 by sublingual tablets. Eight studies involved treatment for less than 6
      months, 10 studies for 6-12 months and 4 studies for greater than 12 months. All
      included studies were double-blind placebo-controlled trials of parallel group
      design. Concealment of treatment allocation was considered adequate in all
      studies and the use of identical placebo preparations was almost universal. There
      was significant heterogeneity, most likely due to widely differing scoring
      systems between studies, for most comparisons. Overall there was a significant
      reduction in both symptoms (SMD -0.34, 95% confidence interval -0.69 to -0.15;
      p=0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p=0.00003)
      following immunotherapy. Subgroup analyses failed to identify a disproportionate
      benefit of treatment according to the allergen administered. There was no
      significant reduction in symptoms and medication scores in those studies
      involving only children but total numbers of participants were small, casting
      doubt on the validity of the conclusion. Increasing duration of treatment does
      not clearly increase efficacy. The total dose of allergen administered may be
      important but insufficient data were available to analyse this factor. REVIEWER'S
      CONCLUSIONS: SLIT is a safe treatment which significantly reduces symptoms and
      medication requirements in allergic rhinitis. The size of this benefit compared
      to that of other available therapies, particularly injection immunotherapy, is
      not clear, having been assessed directly in very few studies. Further research is
      required concentrating on optimising allergen dosage and patient selection.

PMID- 12804443
TI  - Alarm interventions for nocturnal enuresis in children.
AB  - BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful
      condition which affects around 15-20% of five year olds, and up to 2% of young
      adults. OBJECTIVES: To assess the effects of alarm interventions on nocturnal
      enuresis in children, and to compare alarms with other interventions. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group trials register (December
      2002) and the reference lists of relevant articles. Date of the most recent
      searches: December 2002. SELECTION CRITERIA: All randomised or quasi-randomised
      trials of alarm interventions for nocturnal enuresis in children were included,
      except those focused solely on daytime wetting. Comparison interventions included
      no treatment, simple and complex behavioural methods, desmopressin, tricyclics,
      and miscellaneous other methods. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the quality of the eligible trials, and extracted data.
      MAIN RESULTS: Fifty three trials met the inclusion criteria, involving 2862
      children. The quality of many trials was poor, and evidence for many comparisons
      was inadequate. Most alarms used audio methods. Compared to no treatment, about
      two thirds of children became dry during alarm use (RR for failure 0.36, 95% CI
      0.31 to 0.43). Nearly half who persisted with alarm use remained dry after
      treatment finished, compared to almost none after no treatment (RR of failure or
      relapse 45/81 (55%) vs 80/81 (99%), RR 0.56, 95% CI 0.46 to 0.68). There was
      insufficient evidence to draw conclusions about different types of alarm, or
      about how alarms compare to other behavioural interventions. Relapse rates were
      lower when overlearning was added to alarm treatment (RR 1.92, 95% CI 1.27 to
      2.92). Penalties for wet beds appeared to be counter-productive. Alarms using
      electric shocks were unacceptable to children or their parents. Although
      desmopressin may have a more immediate effect, alarms appear more effective by
      the end of a course of treatment (RR 0.71, 95% CI 0.50 to 0.99) and there was
      limited evidence of greater long-term success (RR 4/22 (18%) vs 16/24 (67%),RR
      0.27, 95% CI 0.11 to 0.69). Alarms were better than tricyclics during treatment
      (RR 0.73, 95% CI 0.61 to 0.88) and afterwards (7/12 (58%) vs 12/12 (100%), RR
      0.58, 95% CI 0.36 to 0.94). REVIEWER'S CONCLUSIONS: Alarm interventions are an
      effective treatment for nocturnal bedwetting in children. Alarms appear more
      effective than desmopressin or tricyclics by the end of treatment, and
      subsequently. Overlearning (giving extra fluids at bedtime after successfully
      becoming dry using an alarm) and avoiding penalties may further reduce the
      relapse rate. Better quality research comparing alarms with other treatments is
      needed, including follow-up to determine relapse rates.

PMID- 12804444
TI  - Sympathectomy for neuropathic pain.
AB  - BACKGROUND: Neuropathic pain is defined as pain initiated or caused by a primary
      lesion or dysfunction in the nervous system. Some examples of this condition are
      phantom limb pain, post-stroke pain and complex regional pain syndrome type I
      (reflex sympathetic dystrophy) and type II (causalgia). Treatment options include
      drugs, physical treatments, surgery and psychological interventions. The concept
      that many neuropathic pain syndromes, particularly RSD and causalgia are
      "sympathetically maintained pains" has historically led to attempts to
      temporarily or permanently interrupt the sympathetic nervous system. Chemical
      sympathectomies use alcohol or phenol injections to destroy the sympathetic
      chain, but this effect is temporary until regeneration of the sympathetic chain
      occurs. Surgical ablation can be performed by open removal or electrocoagulation
      of the sympathetic chain, or minimally invasive procedures using stereotactic
      thermal or laser interruption. OBJECTIVES: The review aimed to assess the effects
      of both chemical and surgical sympathectomy for neuropathic pain. Secondary
      objectives were to compare the effects of sympathectomy with no treatment,
      placebo or conventional treatment, and to evaluate whether the technique of
      sympathectomy influences the outcomes of the procedure. SEARCH STRATEGY: We
      searched MEDLINE and EMBASE up to February 2003 and the latest issue of the
      Cochrane Library (Issue 1, 2003). We screened references in the retrieved
      articles, literature reviews and book chapters. We also contacted experts in the
      field of neuropathic pain. SELECTION CRITERIA: Clinical trials and observational
      studies assessing the effects of sympathectomy (surgical or chemical) for
      neuropathic pain of both central or peripheral origin were included. DATA
      COLLECTION AND ANALYSIS: Two reviewers applied the selection criteria to titles
      and abstracts. Full articles of potentially eligible trials were obtained and the
      same reviewers applied the inclusion criteria to the studies. The methodological
      quality of the studies was evaluated. The studies were also evaluated for
      clinical relevance according to a classification developed by our group.
      Statistical pooling was not possible due to heterogeneity of data; instead a
      narrative description of each included study was performed. MAIN RESULTS: We
      included four studies. One randomized trial comparing radiofrequency
      sympatholysis with phenol sympathectomy was rated as low methodological quality
      and it showed that radiofrequency sympatholysis does not offer advantage over
      phenol techniques. However, a modified technique produced sympatholysis
      comparable to that produced by 6% phenol, with less incidence of post
      sympathectomy neuralgia. REVIEWER'S CONCLUSIONS: The practice of surgical and
      chemical sympathectomy is based on poor quality evidence, uncontrolled studies
      and personal experience. Furthermore, complications of the procedure may be
      significant, in terms of both worsening the pain or producing a new pain
      syndrome; and abnormal forms of sweating (compensatory hyperhidrosis and
      pathological gustatory sweating). Therefore, more clinical trials of
      sympathectomy are required to establish the overall effectiveness and potential
      risks of this procedure.

PMID- 12804445
TI  - Antidepressants for cocaine dependence.
AB  - BACKGROUND: Cocaine dependence is a common and serious condition, which has
      become a substantial public health problem. The past decade has witnessed a
      sustained search for an effective pharmacotherapeutic agent for the treatment of
      cocaine dependence. While administration of cocaine acutely increases
      intercellular dopamine, serotonin, and norepinephrine levels by blocking their
      presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine
      systems. Post-cocaine use depression and cocaine craving may be linked to this
      down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels,
      may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria
      and associated craving by general antidepressant action. OBJECTIVES: To conduct a
      systematic review of all RCTs on the use of antidepressants for treating cocaine
      dependence. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register
      (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 
      2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological
      Abstracts (1982 to 2000). Other searches:reference searching; personal
      communication; conference abstracts; unpublished trials from pharmaceutical
      industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA:
      The inclusion criteria for all randomised controlled trials were that they should
      focus on the use of antidepressants on the treatment of cocaine dependence.
      Trials including patients with additional diagnosis such as opiate dependence
      were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the
      data independently and Relative Risks, weighted mean difference and number needed
      to treat were estimated. The reviewers assumed that people who died or dropped
      out had no improvement and tested the sensitivity of the final results to this
      assumption. MAIN RESULTS: 18 studies were included in the review, with 1177
      people randomised. Positive urine sample for cocaine metabolites was the main
      efficacy outcome, with no significant results obtained regardless of the type of
      antidepressant. Compared to other drugs, desipramine performed better but showing
      just a non significant trend with heterogeneity present as revealed by the chi
      square test (8.6, df=3; p=0.04). One single trial showed imipramine performed
      better than placebo in terms of clinical response according to patient's self
      report. A similar rate of patients remaining in treatment was found for both
      patients taking desipramine or placebo. Results from one single trial suggest
      fluoxetine patients on SSRIs are less likely to dropout. Similar results were
      obtained for trials where patients had additional diagnosis of opioid dependence
      and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: There is
      no current evidence supporting the clinical use of antidepressants in the
      treatment of cocaine dependence. Given the high rate of dropouts in this
      population, clinicians may consider adding psychotherapeutic supportive measures
      aiming to keep patients in treatment.

PMID- 12804446
TI  - Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes
      mellitus.
AB  - BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment
      of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study
      indicate that metformin treatment is associated with a reduction in total
      mortality compared to other anti-hyperglycemic treatments. Metformin, however, is
      thought to increase the risk of lactic acidosis, and is considered to be
      contraindicated in many chronic hypoxemic conditions that may be associated with
      lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease,
      and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal
      lactic acidosis with metformin use compared to placebo and other glucose-lowering
      treatments in patients with type 2 diabetes mellitus. A secondary objective was
      to evaluate the blood lactate levels for those on metformin treatment compared to
      placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of
      the Cochrane Controlled Trials Register and the Database of Abstracts of Reviews
      of Effectiveness (up to 4/2000), Medline (up to 11/2000), Embase (up to 11/2000),
      Oldmedline, and Reactions (up to 5/2000), in order to identify all studies of
      metformin treatment from 1966 to November 2000. The Cumulated Index Medicus was
      used to search relevant articles from 1959 to 1965. The search was augmented by
      scanning references of identified articles, and by contacting principal
      investigators. Date of latest search: November 2000. SELECTION CRITERIA:
      Prospective trials in patients with type 2 diabetes that lasted longer than one
      month were included if they evaluated metformin, alone or in combination with
      other treatments, compared to placebo or any other glucose-lowering therapy.
      Observational cohort studies of metformin treatment lasting greater than one
      month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials to be included, assessed study quality and
      extracted data. The incidence of fatal and nonfatal lactic acidosis was recorded
      as cases per patient-years, for metformin treatment and for placebo or other
      treatments. The upper limit for the true incidence of cases in the metformin and
      non-metformin groups were calculated using Poisson statistics. In a second
      analysis lactate levels were measured as a net change from baseline or as mean
      treatment values (basal and stimulated by food or exercise) for treatment and
      comparison groups. The pooled results were recorded as a weighted mean difference
      (WMD) in mmol/L, using the fixed effects model for continuous data. MAIN RESULTS:
      Pooled data from 176 comparative trials and cohort studies revealed no cases of
      fatal or nonfatal lactic acidosis in 35,619 patient-years of metformin use or in
      30,002 patients-years in the non-metformin group. Using Poisson statistics with
      95% confidence intervals the upper limit for the true incidence of metformin
      associated lactic acidosis was 8.4 cases per 100,000 patient-years, and the upper
      limit for the true incidence of lactic acidosis in the non-metformin group was 9
      cases per 100,000 patient-years. There was no difference in lactate levels,
      either as mean treatment levels or as a net change from baseline, for metformin
      compared to placebo or other non-biguanide therapies. The mean lactate levels
      were slightly lower for metformin treatment compared to phenformin (WMD -0.75
      mmol/L, 95% CI -0.86 to -0.15). REVIEWER'S CONCLUSIONS: There is no evidence from
      prospective comparative trials or from observational cohort studies that
      metformin is associated with an increased risk of lactic acidosis, or with
      increased levels of lactate, compared to other anti-hyperglycemic treatments if
      prescribed under the study conditions, taking into account contra-indications.

PMID- 12804447
TI  - Prostacyclin for pulmonary hypertension.
AB  - BACKGROUND: Primary pulmonary hypertension (PPH) is progressive, resulting in
      right ventricular failure. Survival seldom exceeds five years. Pulmonary
      hypertension can be idiopathic or associated with other conditions. It is common
      in patients with diffuse scleroderma and the CREST syndrome where it is
      clinically, haemodynamically and prognostically indistinguishable from idiopathic
      primary pulmonary hypertension. Prostacyclin is a potent vasodilator and
      inhibitor of platelet aggregation. Iloprost is a chemically stable derivative of
      prostacyclin with similar biologic properties and can be given orally, by
      infusion or nebulised. OBJECTIVES: To determine the efficacy of prostacyclin or
      one of its analogues in idiopathic primary pulmonary hypertension. SEARCH
      STRATEGY: A search was carried out using the Cochrane controlled clinical trial
      register. An update search was conducted on 12th August 2002. Four new trials met
      the inclusion criteria of the review. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) involving patients with primary pulmonary hypertension or pulmonary
      hypertension secondary to connective tissue disorders were selected by two
      reviewers. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data
      extracted independently by two reviewers. Outcomes were analysed as continuous
      and dichotomous outcomes, using standard statistical techniques. MAIN RESULTS:
      Seven RCTs of short duration (8-12 weeks) were included. Three compared
      intravenous epoprostenol with conventional therapy. One compared intravenous
      Iloprost with placebo. One RCT compared oral prostacyclin with placebo, another
      compared subcutaneous infusion of treprostinil with placebo and a further RCT
      studied the effects of inhaled iloprost. All the trials showed an improvement in
      exercise capacity. Cardiopulmonary haemodynamics, dyspnoea scores and symptoms
      also improved in some of the studies. Side effects and adverse events related to
      the indwelling catheter (sepsis and thrombosis) were common in intravenous
      trials. The other routes of administration had less severe side effects.
      REVIEWER'S CONCLUSIONS: Intravenous prostacyclin or one of its analogues in
      addition to conventional therapy over 12 weeks appears to improve exercise
      capacity, NYHA functional class and several cardiopulmonary haemodynamic
      variables. There is some evidence that other routes of administration of the drug
      may also be effective with fewer side effects, which were mainly related to the
      indwelling catheter.

PMID- 12804448
TI  - Smoking cessation for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Smoking cessation is the most important treatment for smokers with
      chronic obstructive pulmonary disease (COPD), but little is known about the
      effectiveness of different smoking cessation interventions for this particular
      group of patients. OBJECTIVES: To determine the effectiveness of smoking
      cessation interventions in people with COPD. SEARCH STRATEGY: Electronic searches
      were undertaken on MEDLINE (from 1966 to March 2002), EMBASE (from 1989 to March
      2002) and Psyclit (from 1971 to March 2002), and CENTRAL (Issue 1, 2002).
      SELECTION CRITERIA: Randomised controlled trials in which smoking cessation was
      assessed in participants with confirmed COPD. DATA COLLECTION AND ANALYSIS: Two
      authors extracted the data and performed the methodological quality assessment
      independently for each study, with disagreements resolved by consensus. High
      quality was defined, based on pre-set criteria according to the DelphiList. MAIN
      RESULTS: Five studies were included in this systematic review, two of which were
      of high-quality. The high-quality studies show the effectiveness of psychosocial
      interventions combined with pharmacological intervention compared to no
      treatment: psychosocial interventions combined with nicotine replacement therapy
      (NRT) and a bronchodilator versus no treatment at a 5 year follow-up (RD = 0.16,
      95% CI 0.14 to 0.18), (RR = 4.0, 95% CI 3.25 to 4.93), psychosocial interventions
      combined with NRT and placebo versus no treatment at a 5 year follow-up (RD =
      0.17, 95% CI 0.14 to 0.19), (RR = 4.19, 95% CI 3.41 to 5.15). Furthermore the
      results show the effectiveness of various combinations of psychosocial and
      pharmacological interventions at a 6 months follow-up (RD = 0.07, 95% CI 0.0 to
      0.13), (RR = 1.74, 95% CI 1.01 to 3.0). Unfortunately, none of the included
      studies compared psychosocial interventions with no treatment. Therefore we found
      no evidence with regard to the effectiveness of these interventions. REVIEWER'S
      CONCLUSIONS: Based on this systematic review, the authors found evidence that a
      combination of psychosocial interventions and pharmacological interventions is
      superior to no treatment or to psychosocial interventions alone. Furthermore we
      conclude that there is no clear or convincing evidence for the effectiveness of
      any psychosocial intervention for patients with COPD due to lack of a sufficient
      number of high-quality studies.

PMID- 12804449
TI  - Caudal epidural block versus other methods of postoperative pain relief for
      circumcision in boys.
AB  - BACKGROUND: Circumcision is a commonly performed surgical procedure in boys and
      caudal analgesia is frequently used to minimize discomfort of penile surgery
      postoperatively. For humanitarian and physiological reasons pain should be
      anticipated and effectively controlled while ensuring patient safety. Several non
      caudal analgesic techniques can be used including: penile block, systemic opioids
      and topical local anaesthetic cream,emulsion or gel. OBJECTIVES: To compare the
      relative efficacy and side effects of caudal epidural analgesia with other forms
      of postoperative analgesia following circumcision in boys. SEARCH STRATEGY:
      CENTRAL, MEDLINE (from 1966), and EMBASE are searched using MeSH headings:
      Circumcision, Anesthesia-Caudal, Pediatric or Child, and the text words
      circumcision and caudal. Bibliographies of published trials and conference
      proceedings are also reviewed. Date of last search: December 2002. SELECTION
      CRITERIA: Published randomized and quasi-randomized controlled trials in which
      postoperative analgesia by caudal epidural block is compared with a non-caudal
      method of analgesia, in boys whose mean age is between 28 days and 16 years,
      having elective surgery for circumcision. DATA COLLECTION AND ANALYSIS: Trials
      identified from searching are assessed for inclusion and data extracted
      independently by two reviewers. Review Manager software is used for calculation
      of the treatment effect, represented by relative risks (RR), using a fixed
      effects model with 95% Confidence Intervals (CI). MAIN RESULTS: Seven trials of
      average quality involving 374 patients are included in this review. Only two
      comparisons of caudal analgesia have been investigated; parenteral analgesics in
      six trials, and penile block in one trial. Although some trial heterogeneity is
      evident this does not reach statistical significance. The need for rescue
      analgesia is reduced when caudal analgesia is compared with parenteral
      medications,((RR 0.32(0.16,0.63)). The incidence of nausea and vomiting is
      decreased in caudal patients compared with those receiving parenteral analgesics
      (RR 0.57 (0.35-0.93)) but not with those receiving penile block. REVIEWER'S
      CONCLUSIONS: Few studies compare caudal analgesia with other commonly available
      methods of analgesia in boys having circumcision surgery. Although the need for
      rescue analgesia is reduced in the early postoperative period when caudal is
      compared with parenteral analgesia,evidence from trials may no longer reflect
      current practice and is limited by small numbers and poor methodology. There is a
      need for properly designed trials to study the relative efficacy of caudal
      epidural with other methods such as penile block, morphine, simple analgesics and
      topical local anaesthetic cream,emulsions or gel.

PMID- 12804450
TI  - Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine
      versus other local anaesthetics.
AB  - BACKGROUND: Spinal anaesthesia has been in use since the turn of the late 19th
      century. The most serious complication of this technique is damage to the spinal
      cord or nerve roots resulting in lasting neurologic sequelae. Such serious
      adverse effects seldom happen. There has been an increase in the number of
      reports during the last nine years implicating lidocaine as a possible cause of
      temporary and permanent neurologic complications after spinal anaesthesia. Follow
      up of patients who received uncomplicated spinal anaesthesia revealed that some
      of them developed pain in the lower extremities after an initial full recovery.
      This painful condition that occurs in the immediate post-operative period was
      named "transient neurologic symptoms" (TNS). OBJECTIVES: The objectives of this
      review were to study the frequency of TNS and neurologic complications after
      spinal anaesthesia with lidocaine, compared to other local anaesthetics. SEARCH
      STRATEGY: Trials were identified by computerized searches of the Cochrane
      Controlled Trials Register (4th Quarter 2002), MEDLINE (1966 - January 2003),
      LILAC database, EMBASE (1980 - week 51, 2002), and by checking the reference
      lists of trials and review articles. SELECTION CRITERIA: All randomized and
      pseudo-randomized studies comparing the frequency of TNS and of neurologic
      complications after spinal anaesthesia with lidocaine as compared to other local
      anaesthetics. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated
      the quality of the relevant studies and extracted the data from the included
      studies. MAIN RESULTS: Fourteen trials, reporting 1,349 patients, 117 of whom
      developed transient neurologic symptoms, were included in the analysis. The use
      of lidocaine for spinal anaesthesia increased the risk of developing TNS. There
      was no evidence that this painful condition was associated with any neurologic
      pathology as it was clearly documented that no positive neurologic findings were
      present in any patient with TNS; the symptoms disappeared spontaneously by the
      fifth postoperative day. The relative risk for developing TNS after spinal
      anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine,
      prilocaine, procaine and mepivacaine) was 4.35 (95% Confidence Interval: 1.98,
      9.54). REVIEWER'S CONCLUSIONS: The risk of developing TNS after spinal
      anaesthesia with lidocaine was significantly higher than when bupivacaine,
      prilocaine and procaine were used. The term "TNS", which implies a positive
      neurologic finding, should not be used for this painful condition, which is in
      fact comparable to another common adverse effect after spinal anaesthesia - lower
      back pain. How much the pain in the lower extremities influences patient
      satisfaction is not elucidated clearly in the literature.

PMID- 12804451
TI  - Artemether-lumefantrine for treating uncomplicated falciparum malaria.
AB  - BACKGROUND: Artemether-lumefantrine is being recommended by the World Health
      Organization for treating uncomplicated malaria. It is expensive. We sought
      evidence of its superiority over existing treatment regimens. OBJECTIVES: To
      compare artemether-lumefantrine with other antimalarial drugs for treating
      uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group specialized trials register (February 2003), the
      Cochrane Controlled Trials Register (Issue 1, 2003), MEDLINE (1966 to February
      2003), EMBASE (1988 to February 2003), conference proceedings, and reference
      lists of articles. We contacted experts in malaria research and the
      pharmaceutical company that manufactures artemether-lumefantrine. SELECTION
      CRITERIA: Randomized and quasi-randomized trials comparing artemether
      lumefantrine administered orally with standard treatment regimens (single drug or
      combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied
      inclusion criteria to potentially relevant trials, assessed trial quality, and
      extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and
      day 63 for mefloquine) was the primary outcome. Adverse event information was
      collected from the studies. MAIN RESULTS: Six trials (1698 participants) tested a
      four dose regimen. Failure rates for artemether-lumefantrine tended to be higher
      (comparisons included sulfadoxine-pyrimethamine, halofantrine, and mefloquine;
      difference statistically significant for mefloquine). When compared with
      chloroquine, artemether-lumefantrine was better in two studies, but the failure
      rate for chloroquine at these sites was over 50%. Two trials (419 participants)
      tested a six dose regimen against mefloquine plus artesunate. Artemether
      lumefantrine was associated with higher failure rates but the studies were small.
      REVIEWER'S CONCLUSIONS: The four dose regimen of artemether-lumefantrine seems to
      be less effective than most other current antimalarial regimens. The six dose
      regimen is largely untested.

PMID- 12804452
TI  - Acetyl-L-carnitine for dementia.
AB  - BACKGROUND: Dementia is a common mental health problem affecting 5% of those over
      65. Various pathological processes are linked to memory impairment in dementia,
      particularly those affecting the cholinergic neurotransmitter system. Acetyl-l
      carnitine (ALC) is derived from carnitine and is described as having several
      properties which may be beneficial in dementia. This includes activity at
      cholinergic neurons, membrane stabilization and enhancing mitochondrial function.
      Work on the effects of ALC has been ongoing since the 1980s yet the efficacy of
      ALC in cognitive decline remains unclear. Early studies suggested a beneficial
      effect of ALC on cognition and behaviour in aging subjects. However, later,
      larger studies have not supported these findings. Some of the difficulties lie in
      the early and later studies differing widely in methodology and assessment tools
      used, and are therefore difficult to compare. ALC is not currently in routine
      clinical use. OBJECTIVES: The objective of this review is to establish whether
      Acetyl-l-carnitine is clinically effective in the treatment of people with
      dementia. SEARCH STRATEGY: The trials were identified from a search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on
      8 January 2003 using the terms acetyl-l-carnitine, l-carnitine acetyl ester,
      acetylcarnitine. SELECTION CRITERIA: All double-blind, randomized, trials
      involving people with dementia in which treatment with ALC was compared with a
      placebo group DATA COLLECTION AND ANALYSIS: Data were extracted by a reviewer
      (SH) and entered into Revman 4.1 software. Where possible intention-to-treat data
      were used, but most of the analyses were of completers (people who completed the
      study). MAIN RESULTS: There are 11 included trials, all of which had restricted
      the participants to people with Alzheimer's disease. All trials assessed the
      cognitive effects of ALC and in addition six considered severity of dementia, six
      considered functional ability and six considered clinical global impression.
      There were statistically significant treatment effects in favour of ALC at 12 and
      24 weeks for the numbers showing improvement as determined by Clinical Global
      Impression, [OR 2.33, 95% CI 1.25 to 4.35, P<0.01] and [OR 3.91, 95% CI 1.32 to
      11.54, P=0.01] but not as determined by the CIGIC at 52 weeks. There was no
      evidence of benefit for ALC in the areas of cognition, severity of dementia,
      functional ability or Clinical Global Impression as a continuous measure. Various
      adverse events were reported, but from the meta-analyses there were no
      statistically significant differences between treated and placebo groups.
      REVIEWER'S CONCLUSIONS: There is evidence for benefit of ALC on clinical global
      impression, but there was no evidence using objective assessments in any other
      area of outcome. Given the large number of comparisons made, the statistically
      significant result may be due to chance. At present there is no evidence to
      recommend its routine use in clinical practice. Although the intention of the
      review was to access ALC for the treatment of all dementias, the included trials
      had confined themselves to participants with Alzheimer's disease. Individual
      patient data may add to the findings, as would trials including other types of
      dementia and other outcomes (e.g. mood and caregiver quality of life). However,
      the evidence does not suggest that ALC is likely to prove an important
      therapeutic agent. More work on the pharmacokinetics of ALC in humans is also
      required.

PMID- 12804453
TI  - Care home versus hospital and own home environments for rehabilitation of older
      people.
AB  - BACKGROUND: Rehabilitation for older people has acquired an increasingly
      important profile for both policy-makers and service providers within health and
      social care agencies. This growing demand for rehabilitation services has
      generated an increased interest in the use of alternative care environments, for
      example care home environments, for older persons' rehabilitation. At a time when
      there is pressure for policy decision-makers and service providers to explore the
      use of such care settings for the provision of rehabilitation for older people,
      there appears limited evidence on which to base decisions. OBJECTIVES: The
      objective of this review is to compare the effects of care home environments
      (e.g. nursing home, residential care home and nursing facilities) versus hospital
      environments and own home environments in the rehabilitation of older people.
      SEARCH STRATEGY: The following databases were searched. The Cochrane Effective
      Practice and Organisation of Care Specialised Register, the Cochrane
      Rehabilitation Specialist Register; Cochrane Controlled Trials Register (CCTR);
      MEDLINE (1966-2000); EMBASE (1980-2000), Cumulative Index to Nursing and Allied
      Health Literature (CINAHL) (1982-2000): Science Citation Index (1982-2000);
      Social Science Citation Index (1982-2000); Best Evidence (1991-2000); HMIC (1979
      2000); PsycINFO(1967-2000); ASSIA (1987-2000); Ageline (1978-2000); AgeInfo (1971
      2000); Sociological Abstracts (1963-2000); System for Information on Grey
      Literature (SIGLE) (1980-2000); UK National Research Registers Project Database(
      Issue 1 2001); Architecture Publication Index (1977-2000). The following Journals
      were hand searched: Disability and Rehabilitation (1992-2000); Disability and
      Society (1986-2000); Archives of Physical Medicine and Rehabilitation (1985
      2000); Journal of the American Geriatric Society (1980-2000); International
      Journal of Rehabilitation Research (1980-2000); American Journal of Physical
      Medicine and Rehabilitation (1980-2000) and: Clinical Rehabilitation (1992-2000).
      The reviewers also consulted subject area experts and obtained full text review
      articles and forward tracked any references from these sources. SELECTION
      CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs),
      controlled before and after studies (CBAs) and interrupted time series (ITS) that
      compared rehabilitation outcomes for persons 60 years or older who received
      rehabilitation whilst residing in a care home with those for persons 60 years or
      older who received rehabilitation in hospital or own home environments. Primary
      outcomes included functional outcomes using activities of daily living
      measurement (both personal and instrumental). Secondary outcomes included
      subjective health status; quality of life measures; return to place of usual
      residency; all cause mortality; adverse effects; readmission to an acute care
      facility; patient and carer satisfaction; number of days in facility and number
      of days receiving rehabilitation. DATA COLLECTION AND ANALYSIS: One reviewer (DW)
      completed the initial search and identified potential papers for inclusion.
      Abstracts for these papers were independently scrutinised by two reviewers
      (DW/MS) to assess their eligibility. Full text versions of potentially eligible
      papers were independently assessed by two reviewers (DW/MS). Papers that
      fulfilled the comparison inclusion criteria were then independently scrutinised
      by all reviewers to assess whether they met EPOC methodological criteria for
      inclusion. MAIN RESULTS: The total yield from the initial search strategy was
      19,457. A total of 1,247 abstracts were independently scrutinised by two
      reviewers (DW/MS) to assess their eligibility. Full text papers for 99 studies
      were obtained to assess if they fulfilled the review's comparison inclusion
      criteria. This process resulted in 12 papers being assessed further for
      methodological validity. However, none of these studies met the inclusion
      criteria. REVIEWER'S CONCLUSIONS: There is insufficient evidence to compare the
      effects of care home environments, hospital environments and own home
      environments on older persons rehabilitation outcomes. Although the authors
      acknowledge that absence of effect is not no effect. There are three main
      reasons; the first is that the description and specification of the environment
      is often not clear; secondly, the components of the rehabilitation system within
      the given environments are not adequately specified and; thirdly, when the
      components are clearly specified they demonstrate that the control and
      intervention sites are not comparable with respect to the methodological criteria
      specified by Cochrane EPOC group (Cochrane 1998). The combined effect of these
      factors resulted in the comparability between intervention and control groups
      being very weak. For example, there were differences in the services provided in
      the intervention and control arms, due possibly to differences in dominant
      remuneration systems, nature of the rehabilitation transformation, patient
      characteristics, skill mix and academic status of the care environment.

PMID- 12804454
TI  - Anti-inflammatory treatment for carditis in acute rheumatic fever.
AB  - BACKGROUND: Rheumatic heart disease remains the most important cause of acquired
      heart disease in developing countries. Although the prevention of rheumatic fever
      and the management of recurrences is well established the optimal management of
      active rheumatic carditis is still unclear. OBJECTIVES: To assess the effects of
      anti-inflammatory agents such as aspirin, corticosteroids and immunoglobulin for
      preventing or reducing further heart valve damage in patients with acute
      rheumatic fever. SEARCH STRATEGY: We searched the Cochrane Controlled Trials
      Register (Issue 4, 2000), MEDLINE (1966 to April 2002), EMBASE (1998 to November
      2002), LILACS (1998 to November 2002), Index Medicus (1950 to December 2000) and
      references lists of identified studies. SELECTION CRITERIA: Randomised controlled
      trials comparing anti-inflammatory agents (e.g. aspirin, steroids,
      immunoglobulins) with placebo or controls, or comparing any of the anti
      inflammatory agents with one another, in patients with acute rheumatic fever
      diagnosed according to the Jones, or modified Jones criteria. The presence of
      cardiac disease one year after treatment was the major outcome criteria selected.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and
      assessed trial quality. MAIN RESULTS: Eight randomised controlled trials
      involving 996 people were included. Several steroidal agents viz. ACTH,
      cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous
      immunoglobulin were compared to aspirin, placebo or no treatment in the various
      studies. Six of the trials were conducted between 1950 and 1965, whilst the
      remaining two were done in the last 10 years. Overall there was no significant
      difference in the risk of cardiac disease at one year between the corticosteroid
      treated and aspirin-treated groups (relative risk 0.87, 95% confidence interval
      0.66 to 1.15). Similarly use of prednisone (relative risk 1.78, 95% confidence
      interval 0.98 to 3.34) or intravenous immunoglobulins (relative risk 0.87,
      95%confidence interval 0.55 to 1.39) when compared to placebo did not reduce the
      risk of developing heart valve lesions at one year. REVIEWER'S CONCLUSIONS: There
      is no benefit in using corticosteroids or intravenous immunoglobulins to reduce
      the risk of heart valve lesions in patients with acute rheumatic fever. The
      antiquity of most of the trials restricted adequate statistical analysis of the
      data and acceptable assessment of clinical outcomes by current standards. New
      randomised controlled trials in patients with acute rheumatic fever to assess the
      effects of corticosteroids such as oral prednisone and intravenous
      methylprednisone, and other new anti-inflammatory agents are warranted. Advances
      in echocardiography will allow for more objective and precise assessment of
      cardiac outcomes.

PMID- 12804455
TI  - Bile acids for viral hepatitis.
AB  - BACKGROUND: The viral hepatitides are common causes of liver diseases globally.
      Trials have assessed bile acids for patients with viral hepatitis, but no
      consensus was reached regarding their usefulness. OBJECTIVES: To assess the
      beneficial and harmful effects of bile acids for viral hepatitis. SEARCH
      STRATEGY: Searches were performed of the trial registers of The Cochrane Hepato
      Biliary Group (September 2002), The Cochrane Library (Issue 2, 2002), MEDLINE
      (September 2002), EMBASE (September 2002), and The Chinese Biomedical Database
      (April 2001). SELECTION CRITERIA: Randomised clinical trials comparing any dose
      or duration of bile acids versus placebo or no intervention for viral hepatitis
      were included, irrespective of language, publication status, or blinding. DATA
      COLLECTION AND ANALYSIS: Two reviewers extracted the data independently. The
      methodological quality of the trials was evaluated with respect to generation of
      the allocation sequence, allocation concealment, double blinding, and follow-up.
      The outcomes were presented as relative risks (RR) or weighted mean differences
      (WMD) with 95% confidence intervals (CI). MAIN RESULTS: We identified 27
      randomised trials of bile acids for hepatitis B or C; none were of high
      methodological quality. In one trial, ursodeoxycholic acid (UDCA) versus placebo
      for acute hepatitis B significantly reduced the risk of hepatitis B surface
      antigen positivity at the end of treatment and serum HBV DNA level at the end of
      follow-up. In another trial, UDCA versus no intervention for chronic hepatitis B
      significantly reduced the risk of having abnormal serum transaminase activities
      at the end of treatment. Twenty-five trials compared bile acids (21 trials UDCA;
      four trials tauro-UDCA) versus placebo or no intervention with or without co
      interventions for chronic hepatitis C. Bile acids did not significantly reduce
      the risk of having detectable serum HCV RNA (RR 0.99, 95% CI 0.91 to 1.07),
      cirrhosis, or portal and periportal inflammation score at the end of treatment.
      Bile acids significantly decreased the risk of having abnormal serum alanine
      aminotransferase activity at the end of treatment (RR 0.82, 95% CI 0.76 to 0.90)
      and follow-up (RR 0.91, 95% CI 0.85 to 0.98). Bile acids significantly increased
      the Knodell score (WMD 0.20, 95% CI 0.08 to 0.31) at the end of treatment. No
      severe adverse events were reported. We did not identify trials including
      patients with hepatitis A, acute C, D, or E. REVIEWER'S CONCLUSIONS: Bile acids
      lead to a significant improvement in serum transaminase activities in hepatitis B
      and C. There is insufficient evidence either to support or to refute effects on
      viral markers, mortality, incidence of cirrhosis, or liver histology. Trials with
      high methodological quality are required.

PMID- 12804456
TI  - Treatment for Lambert-Eaton myasthenic syndrome.
AB  - BACKGROUND: Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic
      disorder of neuromuscular transmission. Treatments have attempted to overcome the
      harmful autoimmune process, or to improve residual neuromuscular transmission, in
      order to reverse the principal neurological symptom of muscle weakness.
      OBJECTIVES: The objective was to examine the efficacy of all forms of treatment
      in Lambert-Eaton myasthenic syndrome. SEARCH STRATEGY: We searched the Cochrane
      Neuromuscular Disease Group specialised trials register (September 2002), MEDLINE
      (January 1966 to November 2002) and EMBASE (January 1980 to November 2002). We
      checked the bibliographies in reports of the randomised trials and contacted
      authors to identify additional published or unpublished data. SELECTION CRITERIA:
      Types of studies: all randomised or quasi-randomised trials. TYPES OF
      PARTICIPANTS: all adults and children with a diagnosis of Lambert-Eaton
      myasthenic syndrome, with or without small-cell lung cancer. Types of
      interventions: any form of medical (pharmacological or physical) treatment. Types
      of outcome measures: Primary: change in the muscle strength scale score
      (Quantitative Myasthenia Gravis score), or limb muscle strength measured by
      myometry. Secondary: improvement in the mean amplitude of the resting compound
      muscle action potentials. The mean amplitude used was the mean of all muscles
      tested. DATA COLLECTION AND ANALYSIS: We identified three randomised controlled
      trials. Individual patient data were only available for one trial. MAIN RESULTS:
      The three eligible trials included two controlled trials of the effects of 3,4
      diaminopyridine compared with placebo in a total of 38 patients with Lambert
      Eaton myasthenic syndrome, one of which was of crossover design. A third
      crossover trial compared intravenous immunoglobulin treatment to placebo in nine
      patients with Lambert-Eaton myasthenic syndrome. A meta-analysis of the primary
      endpoint results of these trials was not possible because of differences in
      comparisons and endpoints and, in two trials, lack of individual patient data.
      EFFECTS OF 3,4-DIAMINOPYRIDINE: Two trials of 3,4-diaminopyridine reported a
      significant improvement in the primary endpoint of muscle strength score, or
      myometric limb measurement following treatment. Both trials also reported a
      significant improvement in the secondary endpoint of resting compound muscle
      action potential amplitude following 3,4-diaminopyridine, compared with placebo.
      A meta-analysis of the primary endpoint results was not possible because of
      marked differences in these two trials regarding primary outcome measures.
      However, a meta-analysis of the secondary endpoint (improvement in the amplitude
      of the mean resting compound muscle action potential) was possible. It was
      necessary to assume a known correlation (similarity) of the paired responses for
      each individual in the two treatment periods in order to properly allow for the
      crossover design of one of the two trials (the correlation coefficient was
      assumed to be 0.5 in calculations). Using this approach, meta-analysis revealed a
      significant overall benefit in compound muscle action potential amplitude after
      3,4-diaminopyridine treatment. The overall weighted mean difference was 1.80 mV
      (95% confidence interval 0.82 to 2.78), favouring treatment. These results were
      not sensitive to the assumption made because the overall benefit estimated was
      still significant when the correlation was assumed to be less than 0.1. EFFECTS
      OF INTRAVENOUS IMMUNOGLOBULIN: A crossover trial reported a significant
      improvement in the primary outcome measure of myometric limb strength when
      patients received intravenous immunoglobulin compared to placebo infusions. This
      trial also demonstrated an improvement in the secondary outcome measure of change
      in the mean resting compound muscle action potential amplitude following
      intravenous immunoglobulin, but this improvement did not reach significance.
      Clinical improvement lasted for up to eight weeks. REVIEWER'S CONCLUSIONS:
      Limited evidence from randomised controlled trials showed that either 3,4
      diaminopyridine or intravenous immunoglobulin improved muscle strength scores and
      compound muscle action potential amplitudes in patients with Lambert-Eaton
      myasthenic syndrome. There are insufficient data at present to quantify this
      treatment effect. Other possible treatments, such as plasma exchange, steroids
      and immunosuppressive agents have not been tested in randomised controlled
      trials.

PMID- 12804457
TI  - Biphasic versus triphasic oral contraceptives for contraception.
AB  - BACKGROUND: Side effects caused by oral contraceptives discourage compliance with
      and continuation of oral contraceptives. A suggested disadvantage of biphasic
      compared to triphasic oral contraceptive pills is an increase in breakthrough
      bleeding. We conducted this systematic review to examine this potential
      disadvantage. OBJECTIVES: To compare biphasic with triphasic oral contraceptives
      in terms of efficacy, cycle control, and discontinuation due to side effects.
      SEARCH STRATEGY: We searched computerized databases MEDLINE, EMBASE, POPLINE and
      the Cochrane Controlled Trials Register (CCTR). In addition, we searched the
      reference lists of potentially relevant articles and book chapters. We also
      contacted the authors of relevant studies and pharmaceutical companies in Europe
      and the USA. SELECTION CRITERIA: We included randomized controlled trials
      comparing any biphasic with any triphasic oral contraceptive when used to prevent
      pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the
      various literature searches for possible inclusion and assessed their
      methodological quality using Cochrane guidelines. We contacted the authors of all
      included studies and of possibly randomized studies for supplemental information
      about the study methods and outcomes. We entered the data in RevMan 3.1 and later
      imported it into RevMan 4.1. We calculated Peto odds ratios for incidence of
      incidence of discontinuation due to medical reasons, intermenstrual bleeding,
      absence of withdrawal bleeding, and discontinuation due to intermenstrual
      bleeding. MAIN RESULTS: Only two trials of limited quality met our inclusion
      criteria. Larranaga (1978) compared two biphasic and one triphasic pills, each
      containing levonorgestrel and ethinyl estradiol. No important differences
      emerged, and the frequency of discontinuation due to medical problems was similar
      with all three pills. Percival Smith (1990) compared a biphasic pill containing
      norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel
      (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7).
      The biphasic pill had inferior cycle control compared with the levonorgestrel
      triphasic pill. The odds ratio of cycles with intermenstrual bleeding was 1.7
      (95%CI 1.3-2.2) for the biphasic pill compared with the triphasic levonorgestrel
      pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95%CI 3.1
      13). In contrast, cycle control with the biphasic pill was comparable to that
      with the triphasic pill containing the same progestin (norethindrone). REVIEWER'S
      CONCLUSIONS: The available evidence is limited and of poor quality; the internal
      validity of these trials is questionable. Given the high losses to follow-up
      after randomization, these reports may be better considered observational in
      nature. Given that caveat, the biphasic pill containing norethindrone was
      associated with inferior cycle control compared with the triphasic pill
      containing levonorgestrel. This suggests that the choice of progestin may be more
      important than the phasic regimen in determining bleeding patterns.

PMID- 12804458
TI  - Specialist nurses in diabetes mellitus.
AB  - BACKGROUND: The patient with diabetes has many different learning needs relating
      to diet, monitoring, and treatments. In many health care systems specialist
      nurses provide much of these needs, usually aiming to empower patients to self
      manage their diabetes. The present review aims to assess the effects of the
      involvement of specialist nurse care on outcomes for people with diabetes,
      compared to usual care in hospital clinics or primary care with no input from
      specialist nurses. OBJECTIVES: To assess the effects of diabetes specialist
      nurses / nurse case manager in diabetes on the metabolic control of patients with
      type 1 and type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a
      comprehensive search of databases including the Cochrane Library, MEDLINE and
      EMBASE to identify trials. Bibliographies of relevant papers were searched, and
      hand searching of relevant publications was undertaken to identify additional
      trials (Date of last search November 2002). SELECTION CRITERIA: Randomised
      controlled trials and controlled clinical trials of the effects of a specialist
      nurse practitioner on short and long term diabetic outcomes were included in the
      review. DATA COLLECTION AND ANALYSIS: Three investigators performed data
      extraction and quality scoring independently; any discrepancies were resolved by
      consensus. MAIN RESULTS: Six trials including 1382 participants followed for six
      to 12 months were included. Two trials were in adolescents. Due to substantial
      heterogeneity between trials a meta-analysis was not performed. Glycated
      haemoglobin (HbA1c) in the intervention groups was not found to be significantly
      different from the control groups over a 12 month follow up period. One study
      demonstrated a significant reduction in HbA1c in the presence of the diabetes
      specialist nurse/nurse case manager at 6 months. Significant differences in
      episodes of hypoglycaemia and hyperglycaemia between intervention and control
      groups were found in one trial. Where reported, emergency admissions and quality
      of life were not found to be significantly different between groups. No
      information was found regarding BMI, mortality, long term diabetic complications,
      adverse effects, or costs. REVIEWER'S CONCLUSIONS: The presence of a diabetes
      specialist nurse / nurse case manager may improve patients' diabetic control over
      short time periods, but from currently available trials the effects over longer
      periods of time are not evident. There were no significant differences overall in
      hypoglycaemic episodes, hyperglycaemic incidents, or hospital admissions. Quality
      of life was not shown to be affected by input from a diabetes specialist
      nurse/nurse case manager.

PMID- 12804459
TI  - Open general medical wards versus specialist psychiatric units for acute
      psychoses.
AB  - BACKGROUND: As international healthcare policy has moved away from treating
      people with severe mental illness in large inpatient psychiatric institutions,
      beds for people with acute psychiatric disorders are being established in
      specialised psychiatric units in general hospitals. In developing countries,
      however, limited resources mean that it is not always possible to provide
      discrete psychiatric units, either in general hospitals or in the community. An
      alternative model of admission, used in the Caribbean, is to treat the person
      with acute psychosis in a general hospital ward. OBJECTIVES: To compare the
      outcomes for people with acute psychoses who have been admitted to open medical
      wards with those admitted to conventional psychiatric units. SEARCH STRATEGY: The
      Cochrane Schizophrenia Group's study-based register was searched (November 2001).
      This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library,
      EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference
      proceedings. SELECTION CRITERIA: All relevant randomised or quasi-randomised
      trials, allocating anyone thought to be suffering from an acute psychotic episode
      to either acute management on general medical wards, or acute management in a
      specialist psychiatric unit. The primary outcomes of interest were length of stay
      in hospital and relapse. DATA COLLECTION AND ANALYSIS: Studies were reliably
      selected, assessed for quality, and their data would have been extracted.
      Homogeneous data were to have been synthesised. For binary data, the risk ratios
      (RR) and 95% confidence intervals (CI) were to have been calculated on an
      intention-to-treat basis. If possible, the number needed to treat/harm statistic
      (NNT/H) was to have been calculated. For continuous data, weighted mean
      differences (WMD) were to have been calculated and only data from valid scales
      would have been reported in this review. MAIN RESULTS: We identified no relevant
      randomised trials. REVIEWER'S CONCLUSIONS: The Caribbean practice of treating
      people with severe mental illness on general medical wards has been influenced by
      socio-economic factors rather than evidence from randomised trials. This practice
      affords an opportunity for a well designed, well conducted and reported
      randomised trial, now impossible in many other settings.

PMID- 12804460
TI  - Prophylactic antibiotics for preventing early central venous catheter Gram
      positive infections in oncology patients.
AB  - BACKGROUND: Long-term tunnelled central venous catheters (TCVC) are increasingly
      used in oncology patients. Despite guidelines on insertion, maintenance and use,
      infections remain an important complication. Most infections are caused by Gram
      positive bacteria. Therefore antimicrobial prevention strategies aimed at these
      micro-organisms could potentially decrease the majority of the TCVC infections.
      OBJECTIVES: To determine the efficacy of administering antibiotics prior to
      insertion of a TCVC with or without vancomycin/heparin flush technique in the
      first 45 days after insertion of the catheter to prevent Gram-positive catheter
      related infections in oncology patients. SEARCH STRATEGY: We searched MEDLINE,
      EMBASE,and CENTRAL up to July 2001. Reference lists from relevant articles were
      scanned and conference proceedings were hand searched. The authors of eligible
      studies were contacted to obtain additional information. SELECTION CRITERIA: We
      selected randomized controlled trials giving prophylactic antibiotics prior to
      insertion of the TCVC, and trials using the combination of an antibiotic and
      heparin to flush the TCVC in oncology patients. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed the studies for inclusion, extracted the data
      and assessed the quality. MAIN RESULTS: We included eight trials totalling 527
      patients. Four reported on vancomycin/teicoplanin prior to insertion of the TCVC,
      and four reported on antibiotic flushing combined with heparin. The overall
      effect of an antibiotic prior to catheter insertion decreases the number of Gram
      positive TCVC infections (odds ratio [OR] = 0.55, 95% confidence interval [CI]
      0.29 to1.04). Given an expected infection rate of TCVC during the first 45 days
      of up to 30% this OR implies that the number needed to treat (NNT) will be 10
      (95% CI 4 to13), this means vancomycin needs to be given to 10 patients to
      prevent one TCVC infection. Flushing the TCVC with antibiotics and heparin proved
      to be beneficial (OR = 0.35, 95% CI 0.16 -to 0.77). For intraluminal colonization
      the baseline infection-rate is 15% which leads to a NNT of 13 (95% CI 5 to 23).
      REVIEWER'S CONCLUSIONS: Both interventions lead to a positive overall effect but
      should be considered with care due to the small number of studies. Depending on
      the baseline TCVC infection rate it is justified to administer antibiotics prior
      to the TCVC insertion or to flush the catheter with a combination of an
      antibiotic and heparin, if the catheter-related infection rate is high.

PMID- 12804461
TI  - Dopamine agonists for cocaine dependence.
AB  - BACKGROUND: Cocaine dependence is a common and serious condition, which has
      become nowadays a substantial public health problem. There is a wide and well
      documented range of consequences associated to chronic use of this drug, such as
      medical, psychological and social problems, including the spread of infectious
      diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal
      drug exposure. Therapeutic management of the cocaine addicts includes an initial
      period of abstinence from the drug. During this phase the subjects may
      experience, besides the intense craving for cocaine, symptoms such as depression,
      fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that
      the acute use of cocaine may enhance dopamine transmission and chronically it
      decreases dopamine concentrations in the brain. Pharmacological treatment that
      affects dopamine could theoretically reduce these symptoms and contribute to a
      more successful therapeutic approach. OBJECTIVES: To evaluate the efficacy and
      acceptability of dopamine agonists for treating cocaine dependence. SEARCH
      STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT,
      Biological Abstracts and LILACS; reference searching; personal communication;
      conference abstracts; unpublished trials from pharmaceutical industry; book
      chapters on treatment of cocaine dependence, was performed for the primary
      version of this review in 2001. Another search of the electronic databases was
      done in December of 2002 for this update. The specialised register of trials of
      the Cochrane Group on Drugs and Alcohol was searched until February 2003.
      SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials
      were that they should focus on the use of dopamine agonists on the treatment of
      cocaine dependence. DATA COLLECTION AND ANALYSIS: The reviewers extracted the
      data independently and Relative Risks, weighted mean difference and number needed
      to treat were estimated. The reviewers assumed that people who died or dropped
      out had no improvement and tested the sensitivity of the final results to this
      assumption. MAIN RESULTS: Seventeen studies were included, with 1224 participants
      randomised. Amantadine, bromocriptine, and pergolide were the drugs evaluated.
      The main outcomes evaluated were positive urine sample for cocaine metabolites,
      for efficacy, and retention in treatment, as an acceptability measure. There were
      no significant differences between interventions, and in trials where
      participants had primary cocaine dependence or had additional diagnosis of opioid
      dependence and/or were in methadone maintenance treatment. REVIEWER'S
      CONCLUSIONS: Current evidence does not support the clinical use of dopamine
      agonists in the treatment of cocaine dependence. Given the high rate of dropouts
      in this population, clinicians may consider adding other supportive measures
      aiming to keep patients in treatment.

PMID- 12804462
TI  - Regular self-examination or clinical examination for early detection of breast
      cancer.
AB  - BACKGROUND: Breast self-examination and clinical breast examination have been
      promoted for many years as general screening methods to diagnose breast cancer at
      an earlier stage in order to decrease morbidity and or mortality. The possible
      benefits and harms remain unclear. OBJECTIVES: To determine whether screening for
      breast cancer by regular self-examination or clinical breast examination reduces
      breast cancer mortality and morbidity. SEARCH STRATEGY: The Cochrane Library and
      Medline were searched for randomised trials; date of last search October 2002.
      The specialised register maintained by the Cochrane Breast Cancer Group was
      searched. SELECTION CRITERIA: Randomised clinical trials, including cluster
      randomised trials. DATA COLLECTION AND ANALYSIS: Decisions on which trials to
      include were taken independently by the reviewers based on the methods of trial.
      Disagreements were resolved by discussion. Intention to treat analyses were
      conducted using a fixed effect model with 95% confidence intervals. MAIN RESULTS:
      Two large population-based studies (388,535 women) from Russia and Shanghai that
      compared breast self-examination with no intervention were included. There was no
      statistically significant difference in breast cancer mortality, relative risk
      1.05 (95% confidence interval (CI) 0.90 to 1.24) (587 deaths in total). In
      Russia, more cancers were found in the breast self-examination group than in the
      control group (relative risk 1.24, 95% CI 1.09 to 1.41), while this was not the
      case in Shanghai (relative risk 0.97, 95% CI 0.88 to 1.06). Almost twice as many
      biopsies (3406) with benign results were performed in the screening group
      compared to the control group (1856), relative risk 1.89, 95% CI 1.79 to 2.00.
      REVIEWER'S CONCLUSIONS: Data from two large trials do not suggest a beneficial
      effect of screening by breast self-examination whereas there is evidence for
      harms. There were no randomised trials of clinical breast examination. At
      present, breast self-examination cannot be recommended.

PMID- 12804463
TI  - Folate for depressive disorders.
AB  - BACKGROUND: There are a number of effective interventions for the treatment of
      depression. It is possible that the efficacy of these treatments will be improved
      further by the use of adjunctive therapies such as folate. OBJECTIVES: 1. To
      determine the effectiveness of folate in the treatment of depression 2. To
      determine the adverse effects and acceptability of treatment with folate. SEARCH
      STRATEGY: The Cochrane Controlled Trials Register (CCTR), and the Cochrane
      Collaboration Depression, Anxiety and Neurosis Controlled Trials Register
      (CCDANCTR) incorporating results of group searches of EMBASE, MEDLINE, LILACS,
      CINAHL, PSYNDEX and PsycLIT were searched. Reference lists of relevant papers and
      major textbooks of affective disorder were checked. Experts in the field and
      pharmaceutical companies were contacted regarding unpublished material. SELECTION
      CRITERIA: All randomised controlled trials that compared treatment with folic
      acid or 5'-methyltetrahydrofolic acid to an alternative treatment, whether
      another antidepressant medication or placebo, for patients with a diagnosis of
      depressive disorder (diagnosed according to explicit criteria). DATA COLLECTION
      AND ANALYSIS: Data were independently extracted from the original reports by two
      reviewers. Statistical analysis was conducted using Review Manager version 4.1.
      MAIN RESULTS: Three trials involving 247 people were included. Two studies
      involving 151 people assessed the use of folate in addition to other treatment,
      and found that adding folate reduced Hamilton Depression Rating Scale scores on
      average by a further 2.65 points (95% confidence interval 0.38 to 4.93). Fewer
      patients treated with folate experienced a reduction in their HDRS score of less
      than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number
      needed to treat with folate for one additional person to experience a 50%
      reduction on this scale was 5 (95% confidence interval 4 to 33). One study
      involving 96 people assessed the use of folate instead of the antidepressant
      trazodone and did not find a significant benefit from the use of folate. The
      trials identified did not find evidence of any problems with the acceptability or
      safety of folate. REVIEWER'S CONCLUSIONS: The limited available evidence suggests
      folate may have a potential role as a supplement to other treatment for
      depression. It is currently unclear if this is the case both for people with
      normal folate levels, and for those with folate deficiency.

PMID- 12804464
TI  - Methadone at tapered doses for the management of opioid withdrawal.
AB  - BACKGROUND: Despite widespread use of tapered methadone for detoxification from
      opiate dependence, the evidence of efficacy to prevent relapse and promote
      lifestyle change has not been systematically evaluated. OBJECTIVES: To determine
      whether tapered methadone is effective to manage withdrawal from opioids. SEARCH
      STRATEGY: We searched: Cochrane Controlled Trials Register (Issue 1, 2000),
      MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant
      articles; personal communication; conference abstracts; Internet (NIDA, Clinical
      Trials.org, BMJ). SELECTION CRITERIA: All RCT which focus on the use of tapered
      methadone (max 30 days) versus all other pharmacological detoxification
      treatments, placebo and different modalities of methadone detoxification programs
      for the treatment of opiate withdrawal. DATA COLLECTION AND ANALYSIS: One
      reviewer assessed studies for inclusion and undertook data extraction. Inclusion
      decisions and the overall process were confirmed by consultation between
      reviewers. Qualitative assessments of the methodology of studies were carried out
      using validated checklists. Where possible analysis was carried out according to
      the "intention to treat" principles. MAIN RESULTS: 20 studies were included in
      the review, with 1357 people randomised. Comparisons: 10 studies methadone with
      adrenergic agonists, 7 studies different modalities of methadone detoxification,
      2 studies methadone with other opioid agonists, 1 study methadone with
      chlordiazepoxide, 1 with placebo. The conclusions of the 10 studies that compared
      methadone with adrenergic agonists showed a substantial clinical difference of
      the two treatments in terms of retention in treatment, degree of discomfort and
      detoxification success rates. The conclusions of the 6 studies that compare
      different methadone reduction schedules, showed that different modalities produce
      different responses in terms of time course of withdrawal, severity of withdrawal
      response and in terms of subsequent engagement with treatment. Regarding the
      studies that compare methadone with other opioid agonists, methadyl acetate
      performed similarly to methadone on most process and outcome measures, while
      methadone reduced severity of withdrawal and had fewer drop-outs than did a
      propoxyphene group. Using chlordiazepoxide vs methadone, the two drugs had
      similar results in terms of overall effectiveness. Comparing methadone with
      placebo more severe withdrawal and more drop outs founded in the placebo group.
      The results indicate that tapered methadone and other medications used in the
      included studies are effective in the treatment of the heroin withdrawal
      syndrome, although symptoms experienced by subjects differed according to the
      medication used and the program adopted. Regardless of which medication is
      selected for heroin detoxification, the rates of subsequent heroin abstinence are
      about equal. This suggests that the medications are similar in terms of overall
      effectiveness. Improvements were achieved when other services such as counseling
      and other supporting services were offered contemporaneously with detoxification.
      REVIEWER'S CONCLUSIONS: Data from literature are hardly comparable; programs vary
      widely with regard to duration, design and treatment objectives, impairing the
      application of meta-analysis. Results of many outcomes could not be summarised
      because they were presented either in graphical form or provided only statistical
      tests and p-values. For most studies standard deviation for continuous variables
      were not provided. The studies included in this review confirm that slow tapering
      with temporary substitution of long acting opioids, accompanied by medical
      supervision and ancillary medications can reduce withdrawal severity.
      Nevertheless the majority of patients relapsed to heroin use. However this cannot
      be considered a goal for a detoxification as heroin dependence is a chronic,
      relapsing disorder and the goal of detoxification should be to remove or reduce
      dependence on heroin in a controlled and human fashion and not a treatment for
      heroin dependence.

PMID- 12804465
TI  - Interventions for basal cell carcinoma of the skin.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin malignancy in
      humans. BCCs are defined as slow-growing, locally invasive, malignant (but not
      life threatening), epidermal skin tumours which mainly affect white skinned
      people. The first line treatment is usually surgical excision, but numerous
      alternatives are available. OBJECTIVES: To assess the effects of treatments for
      basal cell carcinoma. SEARCH STRATEGY: We searched the Cochrane Database of
      Systematic Reviews (2002 issue 1) and Cochrane Controlled Trials Register (2002
      issue 1), the Cochrane Skin Group Specialised Register (January 2002), MEDLINE
      (from 1966-2002), EMBASE (from 1980-2002), the Mega Register of Controlled trials
      and the National Research Register (2002 issue 1). In addition the cited
      references of all trials identified and key review articles were searched.
      Pharmaceutical companies were contacted where appropriate for reviews or
      unpublished trials. SELECTION CRITERIA: Inclusion criteria were adults with one
      or more histologically proven, primary basal cell carcinoma. The primary outcome
      measure was recurrence at 3- 5 years, measured clinically. The secondary outcome
      included early treatment failure within 6 months, measured histologically.
      Adverse effect of treatment was evaluated by reviewing aesthetic appearance (to
      patient and blinded observer) and pain during and after treatment. DATA
      COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality
      were carried out by two independent reviewers. MAIN RESULTS: 19 studies (13
      published and 6 abstracts) were identified which include 7 broad therapeutic
      categories. Only one RCT of surgery versus radiotherapy had primary outcome data
      at four years, which showed that there were significantly more persistent tumours
      and recurrences, measured histologically, in the radiotherapy group as compared
      to the surgery group, which translates to an odds ratio of 0.09 (95%CI, 0.01 to
      0.67) in favour of surgery. Cryotherapy, although convenient and less expensive
      than surgery, showed no significant difference in recurrences at one year,
      measured clinically, when compared to surgery, OR 0.23 (0.01 to 6.78). However
      when radiotherapy was compared to cryotherapy there were significantly more
      recurrences at one year, measured histologically, in the cryotherapy group, this
      translates to an odds ratio of 14.80 (95%CI, 3.17 to 69) in favour of
      radiotherapy. Preliminary studies suggest a high success rate (87-88%) for
      imiquimod in the treatment of superficial BCC using a once-daily regimen for 6
      weeks and a useful (76%) treatment response when treating nodular BCC for 12
      weeks, when measured histologically. However this cream has not been compared to
      surgery. REVIEWER'S CONCLUSIONS: There has been very little good quality research
      on efficacy of the treatment modalities used. Most of the trials have looked only
      at BCCs in low risk areas. Surgery and radiotherapy appear to be the most
      effective treatments with surgery showing the lowest failure rates. Other
      treatments might have some use but few have been compared to surgery. Imiquimod
      emerged as a possible new treatment although it has not been compared to surgery
      or any other modality.

PMID- 12804466
TI  - Drug therapies for reducing gastric acidity in people with cystic fibrosis.
AB  - BACKGROUND: Malabsorption of fat and protein contributes to the poor nutritional
      status in people with cystic fibrosis. Impaired pancreatic function may also
      result in increased gastric acidity leading in turn to heartburn, peptic ulcers
      and the impairment of oral pancreatic replacement therapy. The administration of
      gastric reducing agents has been used as an adjunct to pancreatic enzyme therapy
      to improve nutritional status, fat malabsorption and gastro-intestinal symptoms
      in people with cystic fibrosis. It is thus important to establish the current
      level of evidence regarding potential benefits of drug therapies that reduce
      gastric acidity in people with cystic fibrosis. OBJECTIVES: To assess the effect
      of drug therapies for reducing gastric acidity: in improving nutritional status;
      on symptoms associated with increased gastric acidity; fat absorption; lung
      function; quality of life and survival; and to determine if any adverse effects
      are associated with their use. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group trials register which comprises references
      identified from comprehensive electronic database searches, handsearching
      relevant journals and handsearching abstract books and conference proceedings.
      Most recent search of the Group's register: April 2002. SELECTION CRITERIA: All
      randomised and quasi-randomised trials involving agents that reduce gastric
      acidity compared to placebo or a comparator treatment. DATA COLLECTION AND
      ANALYSIS: Both reviewers independently selected trials and assessed trial
      quality. MAIN RESULTS: Thirty-six trials were identified from the initial search.
      Eleven trials with 172 participants were suitable for inclusion. Five trials were
      limited to children and three trials enrolled only adults. One trial found that
      drug therapies which reduce gastric acidity improve gastro-intestinal symptoms
      such as abdominal pain. Five trials reported significant improvement in measures
      of fat malabsorption. Two trials reported no significant improvement in
      nutritional status. Only one trial reported measures of respiratory function and
      one trial reported an adverse effect with prostaglandin E2 analogue misoprostol.
      No trials have been identified which assess the effectiveness of agents that
      reduce gastric acidity in improving quality of life, the complications of
      increased gastric acidity, or survival. REVIEWER'S CONCLUSIONS: Trials have shown
      limited evidence that the agents which reduce gastric acidity in people with
      cystic fibrosis are associated with improvement in gastro-intestinal symptoms and
      fat absorption. Currently, there is insufficient evidence to indicate whether
      there is an improvement in nutritional status, lung function, quality of life, or
      survival. We therefore recommend large, multicentre, randomised controlled
      clinical trials are undertaken to evaluate these interventions.

PMID- 12804467
TI  - Workplace interventions for smoking cessation.
AB  - BACKGROUND: The workplace has potential as a setting through which large groups
      of people can be reached to encourage smoking cessation. OBJECTIVES: To
      categorise workplace interventions for smoking cessation tested in controlled
      studies and to determine the extent to which they help workers to stop smoking or
      to reduce tobacco consumption. SEARCH STRATEGY: We searched the Tobacco Addiction
      Review Group trials register in November 2002, Medline (1966 - November 2002),
      EMBASE (1985 - November 2002) and PsycINFO (to November 2002). We searched
      abstracts from international conferences on tobacco and we checked the
      bibliographies of identified studies and reviews for additional references.
      SELECTION CRITERIA: We categorised interventions into two groups: a)
      Interventions aimed at the individual to promote smoking cessation and b)
      interventions aimed at the workplace as a whole. We applied different inclusion
      criteria for the different types of study. For interventions aimed at helping
      individuals to stop smoking, we included only randomised controlled trials
      allocating individuals, workplaces or companies to intervention or control
      conditions. For studies of smoking restrictions and bans in the workplace, we
      also included controlled trials with baseline and post-intervention outcomes and
      interrupted times series studies. DATA COLLECTION AND ANALYSIS: Information
      relating to the characteristics and content of all kinds of interventions,
      participants, outcomes and methods of the study was abstracted by one reviewer
      and checked by two others. Because of heterogeneity in the design and content of
      the included studies, we did not attempt formal meta-analysis, and evaluated the
      studies using qualitative narrative synthesis. MAIN RESULTS: Workplace
      interventions aimed at helping individuals to stop smoking included nine studies
      of group therapy, three studies of individual counselling, eight studies of self
      help materials and four studies of nicotine replacement therapy. The results were
      consistent with those found in other settings. Group programmes, individual
      counselling and nicotine replacement therapy increased cessation rates in
      comparison to no treatment or minimal intervention controls. Self-help materials
      were less effective. Workplace interventions aimed at the workforce as a whole
      included 13 studies of tobacco bans, two studies of social support, four studies
      of environmental support, four studies of incentives, six studies of
      comprehensive (multi-component) programmes and two studies of competitions and
      recruitment. Tobacco bans decreased cigarette consumption during the working day
      but their effect on total consumption was less certain. We failed to detect an
      increase in quit rates from adding social and environmental support to these
      programmes. There was a lack of evidence that comprehensive programmes reduced
      the prevalence of smoking. Competitions and incentives increased attempts to stop
      smoking, though there was less evidence that they increased the rate of actual
      quitting. REVIEWER'S CONCLUSIONS: We found 1. Strong evidence that interventions
      directed towards individual smokers increase the likelihood of quitting smoking.
      These include advice from a health professional, individual and group counselling
      and pharmacological treatment to overcome nicotine addiction. Self-help
      interventions are less effective. All these interventions are effective whether
      offered in the workplace or elsewhere. Although people taking up these
      interventions are more likely to stop, the absolute numbers who quit are low. 2.
      Limited evidence that participation in programmes can be increased by
      competitions and incentives organised by the employer. 3. Consistent evidence
      that workplace tobacco policies and bans can decrease cigarette consumption
      during the working day by smokers and exposure of non-smoking employees to
      environmental tobacco smoke at work, but conflicting evidence about whether they
      decrease prevalence of smoking or overall consumption of tobacco by smokers. 4. A
      lack of evidence that comprehensive approaches reduce the prevalence of smoking,
      despite the strong theoretical rationale for their use. 5. A lack of evidence
      about the cost-effectiveness of workplace programmes.

PMID- 12804468
TI  - Amantadine for dyskinesia in Parkinson's disease.
AB  - BACKGROUND: Abnormal involuntary movements known as dyskinesias are amongst the
      most disabling side-effects of levodopa therapy. It is thought that amantadine,
      an NMDA-receptor antagonist, may reduce dyskinesias in patients with Parkinson's
      disease without worsening Parkinsonian symptoms. OBJECTIVES: To compare the
      efficacy and safety of adjuvant amantadine therapy versus placebo in treating
      dyskinesia in patients with Parkinson's disease, already established on levodopa,
      and suffering from motor complications. SEARCH STRATEGY: Electronic searches of
      The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001),
      MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993
      2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib
      (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973
      2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990
      2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of
      Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey
      literature was hand searched and the reference lists of identified studies and
      reviews examined. The manufacturers of amantadine were contacted. SELECTION
      CRITERIA: Randomised controlled trials comparing amantadine with placebo in the
      treatment of dyskinesia in patients with a clinical diagnosis of idiopathic
      Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was abstracted
      independently by NC and KD onto standardised forms and disagreements were
      resolved by discussion. MAIN RESULTS: Three randomised controlled trials were
      found comparing amantadine with placebo in the treatment of dyskinesia in
      patients with idiopathic Parkinson's disease. Three trials were excluded on the
      basis that they had no control group and a further three did not state whether
      they randomised the treatment that participants received. The included trials
      were double-blind cross-over studies involving a total of 53 patients. All three
      studies failed to present data from the first arm, instead presenting results as
      combined data from both treatment arms and both placebo arms. Two trials had no
      wash-out interval between the treatment periods. In view of the risk of a carry
      over effect into the second arm, the results of these trials were not analysed.
      The final trial had a one week wash-out interval but only examined 11
      participants. One study reported side-effects of amantadine in 8 of the 18
      participants, including confusion and worsening of hallucinations. Another
      reported reversible edema of both feet in one of eleven participants. REVIEWER'S
      CONCLUSIONS: Due to lack of evidence it is impossible to determine whether
      amantadine is a safe and effective form of treatment for levodopa-induced
      dyskinesias in patients with Parkinson's disease.

PMID- 12804469
TI  - Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low
      birth weight infants.
AB  - BACKGROUND: A patent ductus arteriosus (PDA) complicates the clinical course of
      preterm infants, increasing their risks of developing chronic lung disease (CLD),
      necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH).
      Indomethacin is used as standard therapy to close a PDA, but is associated with
      reduced blood flow to the brain, kidneys and gut. Ibuprofen, another cyclo
      oxygenase inhibitor, may be as effective with fewer side effects. OBJECTIVES: To
      determine the effectiveness and safety of ibuprofen compared to placebo or no
      intervention for closing a PDA in preterm and/or low birth weight infants. To
      determine the effectiveness and safety of ibuprofen compared to other cyclo
      oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA
      in preterm and/or low birth weight infants. SEARCH STRATEGY: Randomized (or quasi
      randomized) controlled trials (RCTs) comparing ibuprofen to placebo or
      indomethacin or mefenamic acid for therapy of PDA were identified by searching
      the Cochrane Controlled Trials Register (Issue 4, 2002), MEDLINE (1996 - January
      2003), CINAHL (1982 - November 2002), EMBASE (1980 - January 2002), reference
      lists of published RCTs and abstracts from the Pediatric Academic Societies and
      the European Society for Pediatric Research meetings published in Pediatric
      Research (1991 - 2002). No language restrictions were applied. SELECTION
      CRITERIA: 1) DESIGN: Randomized or quasi-randomized controlled trials 2)
      POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (<
      2500 grams) with a clinically or echocardiographically diagnosed PDA 3)
      INTERVENTION: Administration of ibuprofen for the closure of PDA 4) OUTCOMES: At
      least one of the following outcomes were reported: failure to close a PDA,
      mortality, surgical ligation, intraventricular haemorrhage (IVH), periventricular
      leukomalacia (PVL), NEC, decreased urine output, retinopathy of prematurity
      (ROP), CLD, sepsis, days on supplementary oxygen. DATA COLLECTION AND ANALYSIS:
      At least two reviewers worked independently at each step of the review, then
      compared results and resolved differences. Methodological quality of eligible
      studies was assessed according to blinding of randomization, of intervention and
      of outcome assessment, and completeness of followup. Weighted treatment effects,
      calculated using Revman 4.1, included typical relative risk (RR), typical risk
      difference (RD), number needed to treat (NNT) or harm (NNH), and weighted mean
      difference (WMD), all with 95% confidence intervals (CI). A fixed effect model
      was used for meta-analyses. Heterogeneity tests were performed to assess the
      appropriateness of pooling the data. MAIN RESULTS: Eight studies including 509
      patients were included. All studies compared the effectiveness of ibuprofen to
      indomethacin for the closure of a PDA. There was no statistically significant
      heterogeneity of treatment effect for any of the outcomes. For the primary
      outcome (failure of ductal closure), there was no statistically significant
      difference between ibuprofen and indomethacin groups [RR 0.92 (95% CI 0.69,
      1.22)]. There were no statistically significant differences in mortality,
      surgical duct ligation, duration of ventilator support, IVH, PVL, NEC, time to
      full enteral feeds, ROP, sepsis, duration of hospital stay or gastrointestinal
      bleed. For many of these outcomes the sample size was small and the estimates
      imprecise. The incidence of decreased urine output (< 1cc/kg/hr) was lower in the
      ibuprofen group as compared to the indomethacin group [NNT 9 (95% CI 5-14)]. This
      was the only statistically significant clinical finding favouring ibuprofen.
      Chronic lung disease defined as oxygen requirement at 28 days post-natally was
      statistically significantly more likely to occur in the ibuprofen group [RR 1.37
      (95% CI 1.01, 1.86); NNH 7 (95% CI 3 - 100)]. No studies comparing ibuprofen
      versus placebo for the closure of PDA were identified. REVIEWER'S CONCLUSIONS: We
      found no statistically significant difference in the effectiveness of ibuprofen
      compared to indomethacin in closing the PDA. Ibuprofen reduces the risk of
      oliguria. However, ibuprofen may increase the risk for chronic lung disease, and
      pulmonary hypertension has been observed in three infants after prophylactic use
      of ibuprofen. Based on currently available information ibuprofen does not appear
      to confer a net benefit over indomethacin for the treatment of a PDA. We conclude
      that indomethacin should remain the drug of choice for the treatment of a PDA.
      Future research may include a four arm trial where infants are randomized at
      birth, either to a prophylaxis arm starting at birth or to an arm in which
      treatment starts after a PDA is diagnosed by echocardiography within the first
      seven days of life. Within the prophylaxis and treatment arms, the infants would
      be randomized to either ibuprofen or indomethacin. The primary outcome should be
      intact survival (survival without handicap) at 18 months corrected age.

PMID- 12804470
TI  - Supplemental oxygen for the treatment of prethreshold retinopathy of prematurity.
AB  - BACKGROUND: Oxygen has long been implicated in the pathogenesis of retinopathy of
      prematurity (ROP) and is rigorously monitored in today's neonatal intensive care
      units. Recent research using a feline model has shown an improvement in ROP
      outcome of kittens treated with supplemental oxygen. Current treatment for ROP by
      retinal ablation is not without complications so a non-invasive method of
      treatment is preferred. The possible effects of long term oxygen supplementation
      on chronic lung disease, length of hospital stay and growth and development are,
      however, unknown. OBJECTIVES: To determine whether, in preterm or low birth
      weight infants with prethreshold ROP, targeting higher as compared to normal
      transcutaneous oxygen levels or pulse oximetry levels when using supplemental
      oxygen reduces the progression of ROP to threshold disease and improves visual
      outcome without any adverse effects. SEARCH STRATEGY: The standard search
      strategy of the Cochrane Neonatal Review Group was used. This included searches
      of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including
      cross references, abstracts, conferences and symposia proceedings, expert
      informants and journal handsearching. An additional literature search of the
      MEDLINE (1966-June 2002), EMBASE (1980-April 2002), and CINAHL (1982-April 2002)
      databases was conducted in order to locate any trials in addition to those
      provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR, The Cochrane
      Library Issue 2, 2002). SELECTION CRITERIA: All randomised or quasi randomised
      studies comparing higher versus normal target oxygen levels in preterm or low
      birthweight infants with prethreshold ROP were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: The methodological quality of the one eligible trial was
      assessed independently by two authors for the degree of selection, performance,
      attrition and detection bias. Data regarding clinical outcomes including
      progression to threshold ROP, blindness or severe visual impairment, mortality,
      respiratory morbidities and long term growth were extracted and reviewed
      independently by two authors. Results were compared and differences resolved as
      required. Data analysis was conducted according to the standards of the Cochrane
      Neonatal Review Group. MAIN RESULTS: The one trial included in this review
      enrolled 649 infants. There was a trend for supplemental oxygen to reduce the
      progression to threshold ROP, however this did not reach statistical significance
      (RR 0.84, 95% CI 0.70, 1.02). A subgroup analysis of those infants without plus
      disease showed significantly fewer infants progressing to threshold ROP in
      infants treated with supplemental oxygen. However this analysis was not pre
      specified so these results should be interpreted with caution. No significant
      effects were detected on blindness or severe visual function at three months
      corrected age, mortality, pneumonia, chronic lung disease or weight gain. Adverse
      pulmonary events were more common in the higher oxygen saturation group and these
      infants were in hospital and on supplemental oxygen for longer. Longer term
      visual outcomes were not reported. REVIEWER'S CONCLUSIONS: The results of this
      systematic review do not show a statistically significant reduction in the rate
      of progression to threshold ROP with supplemental oxygen treatment, but reveal
      increased adverse pulmonary sequelae with higher oxygen targeting in this group
      of preterm infants. Future research needs to be directed towards the question of
      whether infants without plus disease are more likely to respond to supplemental
      oxygen therapy than those with plus disease.

PMID- 12804471
TI  - The effectiveness of psychosocial interventions delivered by general
      practitioners.
AB  - BACKGROUND: Many patients visit their general practitioner (GP) because of
      problems that are psychosocial in origin. However, for many of these problems
      there is no evidence-based treatment available in primary care, and these
      patients place time-consuming demands on their GP. Therefore, GPs could benefit
      from tools to help these patients more effectively and efficiently. In this
      light, it is important to assess whether structured psychosocial interventions
      might be an appropriate tool for GPs. Previous reviews have shown that
      psychosocial interventions in primary care seem more effective that usual care.
      However, these interventions were mostly performed by health professionals other
      than the GP. OBJECTIVES: To present a systematic review of the literature
      addressing the effectiveness of psychosocial interventions by general
      practitioners by assessing the clinical outcomes and the methodological quality
      of selected studies. SEARCH STRATEGY: The literature search was conducted using
      the CCDAN Trials Register, the Cochrane Library and reference lists of relevant
      studies for citation tracking. Also, personal communication with experts took
      place. SELECTION CRITERIA: Randomised controlled trials, controlled clinical
      trials and controlled patient preference trials addressing the effectiveness of
      psychosocial interventions by GPs for any problem or disorder. Studies published
      before January 2002 were eligible for entry. DATA COLLECTION AND ANALYSIS:
      Methodological quality was independently be assessed by two reviewers using the
      Maastricht-Amsterdam Criteria List and the CCDAN Quality Rating Scale. The
      qualitative and quantitative characteristics of selected trials were
      independently extracted by two reviewers using a standardised data extraction
      form. Levels of evidence were used to determine the strength of the evidence
      available. Results from studies that reported similar interventions and outcome
      measures were meta-analysed. MAIN RESULTS: Eight studies were included in the
      review. Selected studies addressed different psychosocial interventions for four
      distinct disorders or health complaints. There is good evidence that problem
      solving treatment by general practitioners is effective for major depression. The
      evidence concerning the remaining interventions for other health complaints
      (reattribution or cognitive behavioural group therapy for somatisation,
      counselling for smoking cessation, behavioural interventions to reduce alcohol
      reduction) is either limited or conflicting. REVIEWER'S CONCLUSIONS: In general,
      there is little available evidence on the use of psychosocial interventions by
      general practitioners. Of the psychosocial interventions reviewed, problem
      solving treatment for depression seems the most promising tool for GPs, although
      a stronger evidence-base is required and the effectiveness in routine practice
      remains to be demonstrated. More research is required to improve the evidence
      base on this subject.

PMID- 12804472
TI  - Cotrimoxazole prophylaxis for opportunistic infections in children with HIV
      infection.
AB  - BACKGROUND: The prevention and early treatment of infections are the mainstay of
      the medical management of the majority of children with HIV infection, who live
      in low income countries without access to antiretroviral drugs. Cotrimoxazole is
      cheap and effective against a wide range of organisms, including Pneumocystis
      carinii pneumonia (PCP) which is an important cause of death and illness in the
      first year of life. It is safe with relatively few side-effects. Diagnosis of HIV
      in children is complicated by the presence of maternal antibodies in early life
      and providing prophylaxis based initially on maternal status is one possible
      solution. However routine prophylactic treatment is difficult to deliver in low
      resource settings, and could also lead to increased resistance to the drug.
      OBJECTIVES: To assess the effects of routinely administered cotrimoxazole on
      death and illness episodes in children with HIV infection, and in infants of HIV
      infected mothers. SEARCH STRATEGY: We searched the Cochrane HIV/AIDS registry,
      MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS
      and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB
      conferences (search date July 2001). We checked reference lists of pertinent
      articles, and contacted pharmaceutical companies and experts in the field.
      SELECTION CRITERIA: Randomised or quasi randomised trials comparing routinely
      administered cotrimoxazole versus placebo or no treatment in children (age less
      than 13 years) with HIV infection, or children less than 18 months with HIV
      infected mothers. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial eligibility and quality. MAIN RESULTS: No studies were found that
      fulfilled the selection criteria. REVIEWER'S CONCLUSIONS: No evidence from
      controlled trials was found of the effect of cotrimoxazole prophylaxis in HIV
      infected children.

PMID- 12804473
TI  - Early skin-to-skin contact for mothers and their healthy newborn infants.
AB  - BACKGROUND: Early skin-to-skin contact involves placing the naked baby prone on
      the mother's bare chest at birth or soon afterwards (< 24 hour). This could
      represent a 'sensitive period' for priming mothers and infants to develop a
      synchronous, reciprocal, interaction pattern, provided they are together and in
      intimate contact. Routine separation shortly after hospital birth is a uniquely
      Western cultural phenomenon that may be associated with harmful effects including
      discouragement of successful breastfeeding. OBJECTIVES: To assess the effects of
      early skin-to-skin contact on breastfeeding, behavior, and physiology in mothers
      and their healthy newborn infants. SEARCH STRATEGY: The Cochrane Pregnancy and
      Childbirth Group and Neonatal Group trials registers (December 2002), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,
      2002), MEDLINE (1976 to 2002). SELECTION CRITERIA: Randomized and quasi
      randomized clinical trials comparing early skin-to-skin contact with usual
      hospital care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. We contacted study authors for additional
      information. We collected adverse effects information from the trials. MAIN
      RESULTS: Seventeen studies, involving 806 participants, were included. We found
      statistically significant and positive effects of early skin-to-skin contact on
      breastfeeding at one to three months postbirth (odds ratio (OR) 2.15, 95%
      confidence interval (CI) 1.10 to 4.22), breastfeeding duration (weighted mean
      difference (WMD) 41.99, 95% CI 13.97 to 70.00), maintenance of infant temperature
      in the neutral thermal range (OR 12.18, 95% CI 2.04 to 72.91), infant blood
      glucose (WMD 11.07, 95% CI 3.97 to 18.17), infant crying (OR 21.89, 95% CI 5.19
      to 92.30) and summary scores of maternal affectionate love/touch (SMD 0.73, 95%
      CI 0.36 to 1.11) during an observed breastfeeding within the first few days
      postbirth. We found no statistically significant benefit of early skin-to-skin
      contact for other major clinical variables: breastmilk maturation, maternal chest
      circumference, infant heart rate. REVIEWER'S CONCLUSIONS: Limitations included
      the methodological quality of the studies, variations in the implementation of
      the intervention and outcome variability. Early skin-to-skin contact appears to
      have some clinical benefit especially regarding breastfeeding outcomes and infant
      crying and has no apparent short or long-term negative effects. Further
      investigation is recommended. To facilitate meta-analysis of the data, future
      research in this area should involve outcome measures consistent with those used
      in the studies included here. Published reports should also clearly indicate if
      the intervention was skin-to-skin contact and include means, standard deviations
      and exact probability values.

PMID- 12804474
TI  - Complementary and alternative therapies for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour and this may contribute towards the popularity of
      complementary methods of pain management. This review examined currently
      available evidence supporting the use of alternative and complementary therapies
      for pain management in labour. OBJECTIVES: To examine the effectiveness of
      complementary and alternative therapies for pain management in labour on maternal
      and perinatal morbidity. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (July 2002), the Cochrane Controlled Trials
      Register (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to July 2002),
      EMBASE (1980 to July 2002) and CINAHL (1980 to July 2002). SELECTION CRITERIA:
      The inclusion criteria included published and unpublished randomised controlled
      trials comparing complementary and alternative therapies with placebo, no
      treatment or pharmacological forms of pain management in labour. All women
      whether primiparous or multiparous, and in spontaneous or induced labour, in the
      first and second stage of labour were included. DATA COLLECTION AND ANALYSIS:
      Meta-analysis was performed using relative risks for dichotomous outcomes and
      weighted mean differences for continuous outcomes. The outcome measures were
      maternal satisfaction, use of pharmacological pain relief and maternal and
      neonatal adverse outcomes. MAIN RESULTS: Seven trials involving 366 women and
      using different modalities of pain management were included in this review. The
      trials included one involving acupuncture (n = 100), one involving audio
      analgesia (n = 25), one involving aromatherapy (n = 22), three trials of hypnosis
      (n = 189) and one trial of music (n = 30). The trial of acupuncture decreased the
      need for pain relief (relative risk (RR) 0.56, 95% confidence interval (CI) 0.39
      to 0.81). Women receiving hypnosis were more satisfied with their pain management
      in labour compared with controls (RR 2.33, 95% CI 1.55 to 4.71). No differences
      were seen for women receiving aromatherapy, music or audio analgesia. REVIEWER'S
      CONCLUSIONS: Acupuncture and hypnosis may be beneficial for the management of
      pain during labour. However, few complementary therapies have been subjected to
      proper scientific study and the number of women studied is small.

PMID- 12804475
TI  - Non-latex versus latex male condoms for contraception.
AB  - BACKGROUND: The male condom, which consists of a thin sheath placed over the
      glans and shaft of the penis, is designed to prevent pregnancy by providing a
      physical barrier against the deposition of semen into the vagina during
      intercourse. Beginning in the 1990s, nonlatex male condoms made of polyurethane
      film or synthetic elastomers were developed as alternative male barrier methods
      for individuals with allergies, sensitivities or preferences that prevented the
      consistent use of condoms made of latex. OBJECTIVES: The review sought to
      evaluate nonlatex male condoms in comparison with latex condoms in terms of
      contraceptive efficacy, breakage, slippage, safety and user preferences. SEARCH
      STRATEGY: We searched the the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE using PubMed, EMBASE, Popline, and LILACS for randomized
      controlled trials of nonlatex condoms. The references of eligible publications
      were assessed for inclusion. We also wrote to the manufacturers of nonlatex
      condoms and known investigators in an attempt to locate any other published or
      unpublished trials not identified in our search. SELECTION CRITERIA: The review
      included all randomized controlled trials identified in the literature search
      that evaluated a male nonlatex condom made of polyurethane film or synthetic
      elastomers in comparison with a latex condom. DATA COLLECTION AND ANALYSIS: We
      evaluated all titles and abstracts located in the literature searches for
      inclusion in the review. Two reviewers independently extracted data from the
      identified studies. We entered and analyzed data with RevMan 4.1. Peto odds
      ratios (ORs) with 95% confidence intervals (CIs) were calculated for the outcomes
      contraceptive efficacy, condom breakage and slippage, discontinuation of use,
      safety and user preference. The number of condoms, men, or women was used as the
      denominator for the ORs. Contraceptive efficacy, early discontinuation, and
      safety outcomes were also measured with survival analysis techniques and entered
      into "Additional tables." MAIN RESULTS: While the eZ.on condom did not protect
      against pregnancy as well as its latex comparison condom, no differences were
      found in the typical-use efficacy in the comparisons between the Avanti and the
      Standard Tactylon and their latex counterparts. The nonlatex condoms were
      associated with higher rates of clinical breakage than their latex comparison
      condoms. The statistically significant odds ratios for clinical breakage for the
      nonlatex condoms versus their latex comparisons ranged from 2.6 (95% CI: 1.6 to
      4.3) to 5.0 (95% CI: 3.6 to 6.8). Few adverse events were reported. In almost all
      of the comparisons, substantial proportions of participants preferred the
      nonlatex condom or reported that they would recommend its use to others.
      REVIEWER'S CONCLUSIONS: Although the nonlatex condoms were associated with higher
      rates of clinical breakage than their latex comparison condoms, the new condoms
      still provide an acceptable alternative for those with allergies, sensitivities
      or preferences that might prevent the consistent use of latex condoms. The
      contraceptive efficacy of the nonlatex condoms requires more research.

PMID- 12804476
TI  - Techniques and materials for skin closure in caesarean section.
AB  - BACKGROUND: Caesarean section is a common operation with no agreed standard on
      operative techniques and materials to use. The skin layer can be repaired by sub
      cuticular stitch immediately below the skin layer, an interrupted stitch or with
      skin staples. A great variety of materials and techniques are used for skin
      closure after caesarean section and there is a need to identify which provide the
      best outcomes for women. OBJECTIVES: To compare the effects of skin closure
      techniques and materials on maternal outcomes and time taken to perform a
      caesarean section. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (August 2002). SELECTION CRITERIA: All
      randomised comparisons of skin closure techniques in caesarean section. DATA
      COLLECTION AND ANALYSIS: Three papers were identified from the search. Data were
      extracted independently by two reviewers. On further inspection two were not
      considered to be randomised controlled trials. MAIN RESULTS: Only one small
      randomised controlled trial, involving 66 women, was included in the review.
      Frishman et al compared staples with absorbable sub-cuticular suture for closure
      following caesarean section. While operating time was significantly shorter when
      using staples, the use of absorbable sub cuticular suture resulted in less
      postoperative pain and yielded a better cosmetic result at the post-operative
      visit. REVIEWER'S CONCLUSIONS: There is no conclusive evidence about how the skin
      should be closed after caesarean section. Questions regarding the best closure
      technique and material and the outcomes associated with each remain unanswered.
      The appearance and strength of the scar following caesarean section is important
      to women and the choice of technique and materials should be made by women in
      consultation with their obstetrician based on the limited information currently
      available.

PMID- 12804477
TI  - Heparin for pregnant women with acquired or inherited thrombophilias.
AB  - BACKGROUND: Thrombophilias, which are associated with a predisposition to
      thrombotic events, have been implicated in adverse obstetrical outcomes such as
      intrauterine growth restriction, stillbirth, severe early onset pre-eclampsia,
      and placental abruption. Heparin administration in pregnancy may reduce the risk
      of these events. OBJECTIVES: The objective of this review was to assess the
      effects of heparin on pregnancy outcomes for women with a thrombophilia. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (July 2002), MEDLINE, EMBASE, CINAHL, Scidex (via OVID Technologies - July 2002)
      and reference lists and personal files. SELECTION CRITERIA: Randomized controlled
      trials comparing heparin with placebo or no treatment, or randomized controlled
      trials comparing any two treatments. Quasi randomized studies would be included.
      DATA COLLECTION AND ANALYSIS: Data would be abstracted from identified studies
      and recorded on a paper form by two reviewers. MAIN RESULTS: No studies were
      included. REVIEWER'S CONCLUSIONS: There are no completed trials to determine the
      effects of heparin on pregnancy outcomes for women with a thrombophilia.

PMID- 12804478
TI  - Antidepressants for generalized anxiety disorder.
AB  - BACKGROUND: Pharmacological treatments have been successfully used to treat
      Generalized Anxiety Disorder (GAD). The mainstay for the pharmacological
      treatment of GAD in past decades has been the use of benzodiazepine and non
      benzodiazepine anxiolytics. Data emerging over the last two decades have shown
      that antidepressants may be equally effective to anxiolytics for treating GAD.
      The use of antidepressants for treating GAD may be advantageous, due to the fact
      that GAD presents a high co morbidity ratio with major depressive disorder (62%)
      and dysthymia (37%). OBJECTIVES: To assess the efficacy and acceptability of
      antidepressants for treating generalized anxiety disorder. SEARCH STRATEGY:
      Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials
      Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and
      Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE
      (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal
      communication; conference abstracts and book chapters on the treatment of
      generalized anxiety disorder. SELECTION CRITERIA: Randomised controlled trials
      were included. Exclusion criteria were: non randomised studies; studies which
      included patients with generalized anxiety disorder and another Axis I co
      morbidity. DATA COLLECTION AND ANALYSIS: The data from studies were extracted
      independently by two reviewers and relative risks, weighted mean difference and
      number needed to treat were estimated. People who died or dropped out were
      regarded as having had no improvement. MAIN RESULTS: Antidepressants (imipramine,
      venlafaxine and paroxetine) were found to be superior to placebo in treating GAD.
      The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not
      differ between antidepressants. Only one study presented data on imipramine and
      trazodone. Imipramine was chosen as the reference drug and, therefore, data on
      trazodone could not be included in the meta analysis. Only one study was
      conducted among children and adolescents (Rynn 2001). The latter study showed
      very promising results of sertraline in children and adolescents with GAD, which
      warrants its replication in larger samples. REVIEWER'S CONCLUSIONS: The available
      evidence suggests that antidepressants are superior to placebo in treating GAD.
      There is evidence from one trial suggesting that paroxetine and imipramine have a
      similar efficacy and tolerability. There is also evidence from placebo-controlled
      trials suggesting that these drugs are well tolerated by GAD patients. Further
      trials of antidepressants for GAD will help to demonstrate which antidepressants
      should be used for which patients.

PMID- 12804479
TI  - Electroconvulsive therapy for the depressed elderly.
AB  - BACKGROUND: Depressive disorder is a common mental disorder in old age, with
      serious health consequences such as increased morbidity, disability, and
      mortality. The frailty of elderly may seriously hamper the efficacy and safety of
      pharmacotherapy in depressed elderly. Electroconvulsive therapy (ECT) in
      depressed elderly therefore may be an alternative to treatment with
      antidepressants. OBJECTIVES: To assess the efficacy and safety of ECT (compared
      to simulated ECT or antidepressants) in depressed elderly. SEARCH STRATEGY: We
      searched the CCDANCTR database, Medline 1966-2000, EMBase 1980-2000, Biological
      abstracts 1985-2000, Cinahl 1982-2000, Lilacs from 1982 onwards, Psyclit 1887
      2000, Sigle 1980-2000. The reference lists of relevant papers were scanned for
      published reports. Hand searching of the Journal of ECT and the Journal of
      Geriatric Psychiatry was done. Based on the title of the publication and its
      abstract, non-eligible citations were excluded. SELECTION CRITERIA: Data were
      independently extracted by at least two reviewers. Randomised, controlled trials
      on depressed elderly (> 60 years) with or without concomitant with conditions
      like cerebrovascular disease, dementia of the Alzheimer's type, vascular dementia
      or Parkinson's disease were included. DATA COLLECTION AND ANALYSIS: Data were
      independently extracted by at least two reviewers. For continuous data weighted
      mean differences (WMD) between groups were calculated. MAIN RESULTS: Randomised
      evidence is sparse. Only three trials could be included, one on the efficacy of
      real ECT versus simulated ECT (O'Leary et al 1994), one on the efficacy of
      unilateral versus bilateral ECT (Fraser 1980) and the other comparing the
      efficacy of ECT once a week with ECT three times weekly (Kellner 1992). All had
      major methodological shortcomings; data were mostly lacking essential information
      to perform a quantitative analysis. Although the O'Leary study concluded that
      real ECT was superior over simulated ECT, these conclusions need to be
      interpreted cautiously. Only results from the second trial (unilateral versus
      bilateral ECT) could be analysed, not convincingly showing efficacy of unilateral
      ECT over bilateral ECT, WMD 6.06 (CI -5.20,17.32). Randomised evidence on the
      efficacy and safety of ECT in depressed elderly with concomitant dementia,
      cerebrovascular disorders or Parkinson's disease is completely lacking. Possible
      side-effects could not be adequately examined because the lack of randomised
      evidence and the methodological shortcomings. REVIEWER'S CONCLUSIONS: None of the
      objectives of this review could be adequately tested because of the lack of firm,
      randomised evidence. Given the specific problems in the treatment of depressed
      elderly, it is of importance to conduct a well designed randomised controlled
      trial in which the efficacy of ECT is compared to one or more antidepressants.

PMID- 12804480
TI  - Bile acids for primary sclerosing cholangitis.
AB  - BACKGROUND: Bile acids have been used for treating primary sclerosing
      cholangitis, but their beneficial and harmful effects remain unclear. OBJECTIVES:
      To assess the beneficial and harmful effects of bile acids for patients with
      primary sclerosing cholangitis. SEARCH STRATEGY: We searched The Cochrane Hepato
      Biliary Group's Trials Register, The Cochrane Library, MEDLINE, EMBASE, and The
      Chinese Biomedical Database generally from inception through to May 2002.
      SELECTION CRITERIA: Randomised clinical trials comparing any dose or duration of
      bile acids versus placebo, no intervention, or another intervention were
      included. Trials were included irrespective of blinding, language, or publication
      status. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data. The
      methodological quality of the trials was evaluated with respect to the generation
      of the allocation sequence, allocation concealment, double blinding, and follow
      up. The results were reported by intention-to-treat analysis. The outcomes were
      presented as relative risks (RR) or weighted mean differences (WMD), both with
      95% confidence intervals (CI). MAIN RESULTS: We identified six randomised
      clinical trials, all with low methodological quality. Patients were treated for
      three months to six years (median two years). Five trials (183 patients) compared
      ursodeoxycholic acid versus placebo, and one trial (40 patients) compared
      ursodeoxycholic acid versus no treatment. Ursodeoxycholic acid did not
      significantly reduce the risk of death (RR 0.86; 95% CI 0.27 to 2.73); treatment
      failure including liver transplantation, varices, ascites, and encephalopathy (RR
      0.94; 95% CI 0.63 to 1.42); liver histological deterioration (RR 0.89; 95% CI
      0.45 to 1.74); or liver cholangiographic deterioration (RR 0.43; 95% CI 0.18 to
      1.02). Ursodeoxycholic acid significantly improved serum bilirubin (WMD -14.6
      micro mol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (WMD -506
      IU/litre; 95% CI -583 to -430), aspartate aminotransferase (WMD -46 IU/litre; 95%
      CI -77 to -16), and gamma-glutamyltranspeptidase (WMD -260 IU/litre; 95% CI -315
      to -205), but not albumin (WMD -0.20 g/litre; 95% CI -1.91 to 1.50).
      Ursodeoxycholic acid was well tolerated. REVIEWER'S CONCLUSIONS: Ursodeoxycholic
      acid leads to a significant improvement in liver biochemistry, but there is
      insufficient evidence to either support or refute its clinical effects in
      patients with primary sclerosing cholangitis. Large scale, high-quality
      randomised clinical trials are needed.

PMID- 12804481
TI  - Surgery for morbid obesity.
AB  - BACKGROUND: Obesity is associated with increased morbidity and mortality. Surgery
      for morbid obesity may be considered when other conventional measures have
      failed, and a number of procedures are available. However, the effects of these
      surgical procedures compared with medical management and with each other are
      uncertain. OBJECTIVES: To assess the effects of surgery for morbid obesity on
      weight, comorbidities and quality of life. SEARCH STRATEGY: We searched the
      Cochrane Controlled Trials Register (issue 4, 2001), Medline (SilverPlatter) up
      to 2001, PubMed (Internet) 01/01/01-19/10/01, Embase (SilverPlatter) up to
      09/2001, PsychINFO up to 10/2001, CINAHL (SilverPlatter) up to 07/2001, Science
      and Social Sciences Citation Index up to 10/12001, British Nursing Index up to
      07/2001, Web of Science Proceedings up to 06/2001, BIOSIS up to10/2001, AMED up
      to 07/2001, National Research Register (issue 2, 2001), reference lists of
      relevant articles, and handsearched relevant journals. We also contacted experts
      in the field. Date of the most recent searches: October 2001. SELECTION CRITERIA:
      Randomised controlled trials comparing different surgical procedures, and
      randomised controlled trials and non-randomised controlled trials comparing
      surgery with non-surgical management for morbid obesity. DATA COLLECTION AND
      ANALYSIS: Data were extracted by one reviewer and checked independently by two
      reviewers. Two reviewers independently assessed trial quality. MAIN RESULTS: 18
      trials involving 1891 people were included. One randomised controlled trial and
      one non-randomised controlled trial compared surgery with non-surgical
      management, and 11 randomised controlled trials compared different surgical
      procedures. The overall quality of the trials was variable, with just one trial
      having adequate allocation concealment. A meta-analysis was not possible due to
      differences in the surgical procedures performed, measures of weight change and
      length of follow-up. Compared with conventional management, surgery resulted in
      greater weight loss (23-28 kg more weight loss at two years), with improvements
      in quality of life and comorbidities. Some complications of surgery occurred,
      such as wound infection. Gastric bypass was associated with greater weight loss
      and fewer revisions, reoperations and/or conversions than gastroplasty, but had
      more side-effects. Greater weight loss and fewer side-effects and reoperations
      occurred with adjustable gastric banding than vertical banded gastroplasty, while
      vertical banded gastroplasty was associated with greater weight loss but more
      vomiting than horizontal gastroplasty. Some postoperative deaths occurred in the
      studies. Weight loss was similar between open and laparoscopic procedures. Fewer
      serious complications occurred with laparoscopic surgery. Laparoscopic surgery
      had a longer operative time, but resulted in reduced blood loss, reduced
      proportion of patients requiring intensive care unit stay, reduced length of
      hospital stay, reduced days to return to activities of daily living and reduced
      days to return to work. REVIEWER'S CONCLUSIONS: The limited evidence suggests
      that surgery is more effective than conventional management for weight loss in
      morbid obesity. The comparative safety and effectiveness of different surgical
      procedures is unclear.

PMID- 12804482
TI  - Reduced dietary salt for prevention of cardiovascular disease.
AB  - BACKGROUND: Restricting sodium intake in elevated blood pressure over short
      periods of time reduces blood pressure. Long term effects (on mortality,
      morbidity or blood pressure) of advice to reduce salt in patients with elevated
      or normal blood pressure are unclear. OBJECTIVES: To assess in adults the long
      term effects (mortality, cardiovascular events, blood pressure, quality of life,
      weight, urinary sodium excretion, other nutrients and use of anti-hypertensive
      medications) of advice to restrict dietary sodium using all relevant randomised
      controlled trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE,
      bibliographies of included studies and related systematic reviews were searched
      for unconfounded randomised trials in healthy adults aiming to reduce sodium
      intake over at least 6 months. Attempts were made to trace unpublished or missed
      studies and authors of all included trials were contacted. There were no language
      restrictions. SELECTION CRITERIA: Inclusion decisions were independently
      duplicated and based on the following criteria: 1) randomisation was adequate; 2)
      there was a usual or control diet group; 3) the intervention aimed to reduce
      sodium intake; 4) the intervention was not multifactorial; 5) the participants
      were not children, acutely ill, pregnant or institutionalised; 6) follow-up was
      at least 26 weeks; 7) data on any of the outcomes of interest were available.
      DATA COLLECTION AND ANALYSIS: Decisions on validity and data extraction were made
      independently by two reviewers, disagreements were resolved by discussion or if
      necessary by a third reviewer. Random effects meta-analysis, sub-grouping,
      sensitivity analysis and meta-regression were performed. MAIN RESULTS: Three
      trials in normotensives (n=2326), five in untreated hypertensives (n=387) and
      three in treated hypertensives (n=801) were included, with follow up from six
      months to seven years. The large, high quality (and therefore most informative)
      studies used intensive behavioural interventions. Deaths and cardiovascular
      events were inconsistently defined and reported; only 17 deaths equally
      distributed between intervention and control groups occurred. Systolic and
      diastolic blood pressures were reduced at 13 to 60 months in those given low
      sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to
      0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium
      excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in
      sodium intake and change in blood pressure were not related. People on anti
      hypertensive medications were able to stop their medication more often on a
      reduced sodium diet as compared with controls, while maintaining similar blood
      pressure control. REVIEWER'S CONCLUSIONS: Intensive interventions, unsuited to
      primary care or population prevention programmes, provide only minimal reductions
      in blood pressure during long-term trials. Further evaluations to assess effects
      on morbidity and mortality outcomes are needed for populations as a whole and for
      patients with elevated blood pressure. Evidence from a large and small trial
      showed that a low sodium diet helps in maintenance of lower blood pressure
      following withdrawal of antihypertensives. If this is confirmed, with no increase
      in cardiovascular events, then targeting of comprehensive dietary and behavioural
      programmes in patients with elevated blood pressure requiring drug treatment
      would be justified.

PMID- 12804483
TI  - Infant position in neonates receiving mechanical ventilation.
AB  - BACKGROUND: Several body positions other than standard supine position have been
      used in patients undergoing intensive care for reducing the incidence of pressure
      ulcers of the skin, contractures or ankylosis and for improving the patient's
      well being. In patients from different age groups undergoing mechanical
      ventilation (MV), it has been observed that particular positions such as prone
      position may improve some respiratory parameters. Benefits from these positions
      have not been clearly defined in Neonatology, a field where it is common that
      patients require mechanical ventilation sometimes during extended time periods.
      OBJECTIVES: To assess the effects on both short and long-term outcomes of
      different positioning of newborn infants receiving MV. SEARCH STRATEGY: Databases
      searched (up to January 2002) were the Oxford Database of Perinatal Trials,
      CINAHL, MEDLINE, EMBASE and Cochrane Controlled Trials Register (The Cochrane
      Library, Issue 1, 2002). Hand searches of proceedings of the Society for
      Pediatric Research from 1990 to January 2002 were used to identify unpublished
      studies. SELECTION CRITERIA: Randomised or quasi randomised clinical trials
      comparing different positions in newborns receiving mechanical ventilation. DATA
      COLLECTION AND ANALYSIS: Three independent and unblinded reviewers assessed the
      trials for inclusion in the review and extracted the data. Data were double
      checked and entered into the Review Manager software. MAIN RESULTS: Ten trials
      involving 164 infants were included in this review. Several positions were
      compared: prone vs. supine, prone vs. lateral right, lateral right vs. supine,
      lateral left vs. supine, lateral right vs. lateral left and good lung dependent
      vs. good lung uppermost. Apart from one of the two studies that compared lateral
      right vs. lateral left positions, all the included studies had a crossover
      design. Comparing prone vs. supine position, an increase in arterial P02 in the
      prone position of between 2.75 and 9.72 mm Hg (95%CI) was observed (one trial).
      When % hemoglobin oxygen saturation was measured with pulse oximetry, improvement
      in the prone position was from 1.17 to 4.36% (typical effect based on four
      trials). It was not possible to establish whether this effect remained once the
      intervention was stopped. Negative effects from the interventions were not
      described, although this issue was not studied enough. Effects of position on
      other outcomes were not statistically significant; however, these cannot be
      excluded considering the small numbers that were studied. REVIEWER'S CONCLUSIONS:
      The prone position was found to slightly improve the oxygenation in neonates
      undergoing mechanical ventilation. However, we found no evidence concerning
      whether particular body positions during mechanical ventilation of the neonate
      are effective in producing sustained and clinically relevant improvements.

PMID- 12804484
TI  - Patient education for adults with rheumatoid arthritis.
AB  - BACKGROUND: Because of the unpredictability people with arthritis face on a daily
      basis, patient education programmes have become an effective complement to
      traditional medical treatment giving people with arthritis the strategies and the
      tools necessary to make daily decisions to cope with the disease. OBJECTIVES: To
      assess the effectiveness of patient education interventions on health status in
      patients with rheumatoid arthritis. SEARCH STRATEGY: We searched MEDLINE, EMBASE
      and PsycINFO and the Cochrane Controlled Trials Register. A selection of review
      articles (see references) were examined to identify further relevant
      publications. There was no language restriction. SELECTION CRITERIA: Randomised
      controlled trials (RCT's) evaluating patient education interventions that
      included an instructional component and a non-intervention control group; pre-
      and post-test results available separately for RA, either in the publication or
      from the studies' authors; and study results presented in full, end-of-study
      report. MAIN RESULTS: Thirty-one studies with relevant data were included. We
      found significant effects of patient education at first follow-up for scores on
      disability, joint counts, patient global assessment, psychological status, and
      depression. A trend favouring patient education was found for scores on pain.
      Physician global assessment was not assessed in any of the included studies. The
      dimensions of anxiety and disease activity showed no significant effects. At
      final follow up no significant effects of patient education were found, although
      there was a trend favouring patient education for scores on disability.
      REVIEWER'S CONCLUSIONS: Patient education as provided in the studies reviewed
      here had small short-term effects on disability, joint counts, patient global
      assessment, psychological status and depression. There was no evidence of long
      term benefits in adults with rheumatoid arthritis.

PMID- 12804485
TI  - Art therapy for schizophrenia or schizophrenia-like illnesses.
AB  - BACKGROUND: Medication is the mainstay of treatment for schizophrenia or
      schizophrenia-like illnesses. Many people, however, continue to experience
      symptoms in spite of medication. In addition to medication, creative therapies,
      such as art therapy may be helpful. Art therapy allows exploration of the
      patient's inner world in a non-threatening way through a therapeutic relationship
      and the use of art materials. It was mainly developed in adult psychiatric
      inpatient units and was designed for use with people in whom verbal psychotherapy
      would be impossible. OBJECTIVES: To review the effects of art therapy as an
      adjunctive treatment for schizophrenia compared with standard care and other
      psychosocial interventions. SEARCH STRATEGY: We searched the Cochrane
      Schizophrenia Group's Register (May 2002), hand searched reference lists and
      'Inscape' (the Journal of the British Association of Art Therapists), and
      contacted relevant authors. SELECTION CRITERIA: All randomised controlled trials
      that compared art therapy with standard care or other psychosocial interventions
      for schizophrenia. DATA COLLECTION AND ANALYSIS: Studies were reliably selected,
      quality assessed and data extracted. Data were excluded where more than 50% of
      participants in any group were lost to follow up. For binary outcomes we
      calculated a fixed effects risk ratio (RR) and its 95% confidence interval (CI).
      MAIN RESULTS: The search identified 57 reports but only two studies (total n=137)
      met the inclusion criteria. Both compared art therapy plus standard care with
      standard care alone. Fewer people allocated to art therapy left the study before
      20 weeks compared with those given standard care alone (n=47, 1 RCT, RR 0.34 CI
      0.15 to 0.8, NNT 3 CI 1.5 to 7). Measures of change in mental state,
      interpersonal relationships and social networking were reported but the data were
      too problematic to interpret with confidence. Much data was lost due to poor
      reporting or inappropriate use of scales. REVIEWER'S CONCLUSIONS: Randomised
      studies have been proven to be possible in this field. The use of art therapy for
      serious mental illnesses should continue to be under evaluation as its benefits,
      or harms, are unclear.

PMID- 12804486
TI  - Anticholinergics for symptomatic management of Parkinson's disease.
AB  - BACKGROUND: Anticholinergics were the first drugs available for the symptomatic
      treatment of Parkinson's disease and they are still widely used today, both as
      monotherapy and as part of combination regimes. They are commonly believed to be
      associated with a less favourable side effect profile than other antiparkinsonian
      drugs, in particular with respect to neuropsychiatric and cognitive adverse
      events. They have been claimed to exert a better effect on tremor than on other
      parkinsonian features. OBJECTIVES: To determine the efficacy and tolerability of
      anticholinergics in the symptomatic treatment of Parkinson's disease compared to
      placebo or no treatment. SEARCH STRATEGY: The literature search included
      electronic searches of the Cochrane Controlled Trials Register (The Cochrane
      Library, Issue 4, 2001), MEDLINE (1966 to 2001), Old Medline (1960-1965), Index
      Medicus (1927 - 1959), as well as handsearching the neurology literature
      including the reference lists of identified articles, other reviews and book
      chapters. SELECTION CRITERIA: Randomised controlled trials of anticholinergic
      drugs versus placebo or no treatment in de-novo or advanced Parkinson's disease,
      either as monotherapy or as an add-on to other antiparkinsonian drugs were
      included. Trials of anticholinergic drugs that were never in general clinical use
      were excluded. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by
      two authors. Differences were settled by discussion among all authors. Data
      collected included patient characteristics, disease duration and severity,
      concomitant medication, interventions including duration and dose of
      anticholinergic treatment, outcome measures, rates of and reasons for
      withdrawals, and neuropsychiatric and cognitive adverse events. MAIN RESULTS: The
      initial search yielded 14 potentially eligible studies, five of which were
      subsequently excluded. In three cases this was because they dealt with substances
      that had never been marketed or had not been licensed for as far as could be
      traced back. One trial had been published twice in different languages. One study
      was excluded based on the assessment of its methodological quality. The remaining
      nine studies were all of double-blind cross-over design and included 221
      patients. Trial duration was between five and 20 weeks and drugs investigated
      were benzhexol (mean doses: 8 to 20 mg/d), orphenadrine (mean dose not reported),
      benztropine (mean dose not reported), bornaprine (8 to 8.25 mg/d), benapryzine
      (200 mg/d), and methixine (45 mg/d). Only one study involved two anticholinergic
      drugs. Outcome measures varied widely across studies and in many cases, the
      scales applied were the authors' own and were not defined in detail. Incomplete
      reporting of methodology and results was frequent. The heterogeneous study
      designs as well as incomplete reporting precluded combined statistical analysis.
      Five studies used both tremor and other parkinsonian features as outcome
      measures. Outcome measures in these five studies were too different for a
      combined analysis and results varied widely, from a significant improvement in
      tremor only to significant improvement in other features but not in tremor. All
      studies except one (dealing with methixine) found a significant improvement from
      baseline on the anticholinergic drug in at least one outcome measure. The
      difference between placebo and active drug was reported in four studies and was
      found to be significant in all cases. No study failed to show superiority of the
      anticholinergic over placebo. The occurrence of neuropsychiatric and cognitive
      adverse events was reported in all but three studies (in 35 patients on active
      drug versus 13 on placebo). The most frequently reported reason for drop-outs
      from studies was in patients on placebo due to withdrawal from pre-trial
      anticholinergic treatment. REVIEWER'S CONCLUSIONS: As monotherapy or as an
      adjunct to other antiparkinsonian drugs, anticholinergics are more effective than
      placebo in improving motor function in Parkinson's disease. Neuropsychiatric and
      cognitive adverse events occur more frequently on anticholinergics than on
      placebo and are a more common reason for withdrawal than lack of efficacy.
      Results regarding a potentially better effect of the anticholinergic drug on
      tremor than on other outcome measures are conflicting and data do not strongly
      support a differential clinical effect on individual parkinsonian features. Data
      is insufficient to allow comparisons in efficacy or tolerability between
      individual anticholinergic drugs.

PMID- 12804487
TI  - Interventions for intermittent distance exotropia.
AB  - BACKGROUND: The clinical management of intermittent distance exotropia has been
      discussed frequently in the literature but there is a lack of clarity regarding
      the indications for intervention, the most effective type and the optimum age at
      which it should be carried out. OBJECTIVES: The objective of this review is to
      assess intervention criteria, the effects of various surgical and non-surgical
      treatments in people with intermittent distance exotropia and to determine the
      significance of factors such as age with respect to outcome. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials - CENTRAL (which
      contains the Cochrane Eyes and Vision Group trials register) on the Cochrane
      Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE (1980 to November
      2002) and LILACS (Latin American and Caribbean Literature on Health Sciences)
      (1966 to 2002). We manually searched the British Orthoptic Journal, proceedings
      of the European Strabismological Association (ESA), International
      Strabismological Association (ISA) and American Academy of Paediatric
      Ophthalmology and Strabismus meeting (AAPOS). We contacted researchers who are
      active in the field for information about further published or unpublished
      studies. There were no language restrictions in the manual or electronic
      searches. SELECTION CRITERIA: We planned to include randomised controlled trials
      of any surgical or non-surgical treatment for intermittent distance exotropia.
      DATA COLLECTION AND ANALYSIS: Each reviewer independently assessed study
      abstracts identified from database and manual searches. Reviewer analysis was
      then compared and full papers for appropriate studies were obtained. MAIN
      RESULTS: No studies were found that met our selection criteria and therefore none
      were included for analysis. REVIEWER'S CONCLUSIONS: The available literature
      consists mainly of retrospective case reviews. These are difficult to compare and
      analyse due to a large variation in the definition of intermittent distance
      exotropia, intervention criteria and outcome measures. However there seems to be
      general agreement that non-surgical treatment is most appropriate in small angle
      deviations or as a supplement to surgery. Studies were found supporting both
      early and late surgical intervention so the optimal timing of surgical
      intervention cannot be concluded. Recent work indicates that bilateral surgery
      may be the most effective surgical procedure in these cases. There is clearly a
      need for carefully planned clinical trials to be undertaken to improve the
      evidence base for the management of this condition.

PMID- 12804488
TI  - Indomethacin for asymptomatic patent ductus arteriosus in preterm infants.
AB  - BACKGROUND: Patent Ductus Arteriosus (PDA remains a significant cause of
      mortality and morbidity in premature infants. Indomethacin is an effective
      treatment to close a PDA, and has been used for many years with several treatment
      regimes, including prophylactic use in all at risk premature infants. There are
      however concerns regarding adverse side effects of indomethacin. By targeting a
      group of infants with an asymptomatic PDA, rather than treating all VLBW infants
      prophylactically, indomethacin use would be restricted, limiting the possibility
      of significant side effects to those with greater chance of benefit. OBJECTIVES:
      To assess whether in premature neonates with asymptomatic PDA, treatment with
      indomethacin improves short and long term outcomes; in particular: incidence of
      symptomatic PDA, mortality, chronic neonatal lung disease (CLD), intraventricular
      haemorrhage (IVH), retinopathy of prematurity (ROP), neurodevelopmental outcome,
      length of ventilation. SEARCH STRATEGY: Standard strategies of the Cochrane
      Neonatal Review Group were used. Searches were made of the Oxford Database of
      Perinatal Trials, MEDLINE and EMBASE from 1966 to September 2002, CINAHL from
      1982 to September 2002, and the Cochrane Controlled Trials Register
      (CENTRAL/CCTR) in The Cochrane Library, Issue 3, 2002. Searches were also made of
      previous reviews including cross-referencing, abstracts, and conference and
      symposia proceedings published in Pediatric Research. SELECTION CRITERIA: All
      randomised controlled trials of indomethacin compared with placebo or no
      intervention for the treatment of asymptomatic PDA in premature infants were
      eligible. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal
      Review Group were used. Trials identified by the search strategy were
      independently reviewed by each author and assessed for eligibility and trial
      quality. Data were then extracted independently by each author and compared, with
      any differences resolved following discussion. Any additional information
      required was requested from trial authors. Only published data was available for
      review. Results are expressed as typical relative risk and typical risk
      difference for dichotomous outcomes, and weighted mean difference for continuous
      variables. MAIN RESULTS: Three small trials involving a total of 97 infants were
      included. Meta analysis of combined data was possible for seven outcomes.
      Treatment of an asymptomatic PDA with indomethacin significantly reduced the
      incidence of symptomatic PDA (RR 0.36, 95% CI 0.19, 0.68) and duration of
      supplemental oxygen (WMD -12.5, 95% CI -23.8, -1.26). There was no evidence of
      effect on mortality (RR 1.32, 95% CI 0.45, 3.86), CLD (RR 0.91, 95% CI 0.62,
      1.35), IVH (RR 1.21, 95% CI 0.62, 2.37), ROP (RR 0.68, 95% CI 0.26, 1.78), or
      length of ventilation (WMD -7.00 days, 95%CI -17.33, 3.34). Long term
      neurodevelopmental outcomes were not reported. One trial reported a significant
      reduction in the duration of supplemental oxygen following treatment with
      indomethacin in the subgroup of infants with birth weight less than 1000g.
      REVIEWER'S CONCLUSIONS: This review demonstrates a significant decrease in the
      incidence of symptomatic PDA following treatment of an asymptomatic PDA with
      indomethacin. There is also a small but statistically significant decrease in the
      duration of requirement for supplemental oxygen. There are no reported long term
      outcomes in the included trials, and so it is not possible to comment on possible
      long term effects. Further studies are required to determine the long term
      benefits or harms of closing a PDA prior to the onset of symptoms.

PMID- 12804489
TI  - Communication skills training for health care professionals working with cancer
      patients, their families and/or carers.
AB  - BACKGROUND: Research suggests communication skills do not reliably improve with
      experience and considerable effort is dedicated to courses improving
      communication skills for health professionals. The evaluation of such courses is
      of importance to enable evidence-based teaching and practice. OBJECTIVES: To
      assess whether communication skills training is effective in changing behaviour
      of health professionals in cancer care with regard to communication/interaction
      with patients. SEARCH STRATEGY: We searched CENTRAL (Cochrane Library Issue 3
      2001), MEDLINE (1966 to November 2001), EMBASE (1980 to November 2001), PsycInfo
      (1887 to November 2001), CINAHL (1982 to November 2001), AMED (1985 - October
      2001), Dissertation Abstracts International (1861 to March 2002) and EBM Reviews
      (1991 to March/April 2001). Reference lists of relevant articles were searched.
      SELECTION CRITERIA: Randomized controlled trials or controlled before and after
      studies of communication skills training in cancer health professionals,
      measuring changes in behaviour/skills using objective and validated scales. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. MAIN RESULTS: Although 2822 references were considered, only two
      trials involving 232 health professionals were included. One provided an
      intensive three-day course then assessed oncology doctors interacting with a
      total of 640 patients; the other provided a modular course then used role plays
      with oncology nurses for skill assessment. In one trial, course attendees used
      more focused questions (34% increase, probability < 0.005), focused and open
      questions (27% increase, p = 0.005), expressions of empathy (69% increase, p <
      0.005) and appropriate responses to cues (38% increase, p < 0.05) at follow up
      than non-attendees. No significant differences were found between attendees and
      non-attendees in use of leading questions. From baseline to follow up in the same
      study, attendees had significantly different changes in rates of leading
      questions (relative risk 0.72, p < 0.05), focused questions (Relative Risk 1.25,
      p < 0.005), open questions (RR 1.17, p < 0.05) and empathy (RR 1.50, p = 0.005).
      The only significant difference in observed communication skills in the second
      trial was that the trained group were more in control of the follow-up interview
      than the untrained group (p < 0.05). Both studies investigated differences in
      summarising, interrupting and checking but found none. REVIEWER'S CONCLUSIONS:
      The training programmes assessed by these trials appear to be effective in
      improving cancer care professionals communication skills. It is not known whether
      the training would be effective if taught by other educators, nor has any trial
      compared the efficacy of both programmes.

PMID- 12804490
TI  - Antibiotic prophylaxis for hernia repair.
AB  - BACKGROUND: The use of antibiotic prophylaxis for hernia repair is currently a
      controversial issue given the disparity among study results in this area.
      OBJECTIVES: The objective of this systematic review was to clarify the
      effectiveness of antibiotic prophylaxis in reducing postoperative wound infection
      rates in elective open inguinal hernia repair. SEARCH STRATEGY: Searches in the
      Cochrane Colorectal Cancer Group specialized register were conducted crossing the
      terms herni* and inguinal or groin and the terms antimicr* or antibiot*, as free
      text and MeSH terms. A similar search in Medline (WebSPIRS from Silver Platter,
      January/1966 to November/2002) and Embase (1976 to December/2002) were conducted
      using the following terms: #1 antibiotic* or antimicrob* or anti infecti* or
      antiinfecti*; #2 prophyla* or prevent*; #3 #1 and #2; #4 clean and (surgery or
      tech* or proced*); #5 herni*; #6 (wound infection) and #4; #7 #3 and (#4 or #5 or
      #6). Reference lists of the included studies were checked to identify additional
      studies. SELECTION CRITERIA: Only randomized clinical trials were included. DATA
      COLLECTION AND ANALYSIS: Seven randomized clinical trials were identified. Two of
      them used prosthetic material for hernia repair (hernioplasty) whereas the
      remaining studies did not (herniorraphy). Pooled and subgroup analysis were
      conducted depending on whether prosthetic material was or not used. A random
      effects model was used in the analysis. MAIN RESULTS: The total number of
      patients included was 2660 (treatment group: 1297, control group: 1363). Overall
      infection rates were 3.08% and 4.69% in the prophylaxis and control groups,
      respectively (OR 0.61, 95%CI 0.32 - 1.17). The number of patients who need to be
      treated with prophylaxis (NNT) to prevent one infection in at least 30 days was
      50 (95%CI 25 to infinite). The subgroup of patients with herniorrhaphy had
      infection rates of 3.78% and 4.87% in the prophylaxis and control groups,
      respectively (OR 0.84, 95%CI 0.53 - 1.34). NNT was 100 (95%CI 34 - infinite). The
      subgroup of patients with hernioplasty had infection rates of 1.3% and 4.2% in
      the prophylaxis and control groups, respectively (OR 0.28, 95%CI 0.02 - 3.14).
      NNT is 25 (IC95% NNH 25 to NNT 8). REVIEWER'S CONCLUSIONS: Based on the results
      of this meta-analysis, there was no clear evidence that routine administration of
      antibiotic prophylaxis for elective inguinal hernia repair reduced infection
      rates.

PMID- 12804491
TI  - Epinephrine for the resuscitation of apparently stillborn or extremely
      bradycardic newborn infants.
AB  - BACKGROUND: Epinephrine is a cardiac stimulant with complex effects on the heart
      and blood vessels. It has been used for decades in all age groups to treat
      cardiac arrest and bradycardia. Despite formal guidelines for the use of
      epinephrine in neonatal resuscitation, the evidence for these recommendations has
      not yet been rigorously scrutinised. While it is understood that this evidence is
      in large part derived from animal models and the adult human population, the
      contribution from work in the neonatal population remains unclear. In particular,
      it remains to be determined if any randomised studies in neonates have helped to
      establish if the administration of epinephrine in the context of apparent
      stillbirth or extreme bradycardia might influence mortality and morbidity.
      OBJECTIVES:  PRIMARY OBJECTIVE: ~bullet~To determine if the administration of
      epinephrine to apparently stillborn and extremely bradycardic newborns reduces
      mortality and morbidity Secondary objectives: ~bullet~To determine the effect of
      intravenous versus endotracheal administration on mortality and morbidity
      ~bullet~To determine the effect of high dose versus standard dose epinephrine on
      mortality and morbidity, where high dose is defined as any dose greater than the
      current recommended standard dose of 0.1 to 0.3ml/kg of a 1:10,000 solution of
      epinephrine ~bullet~To determine whether the effect of epinephrine on mortality
      and morbidity varies with gestational age, i.e. term (greater than or equal to 37
      weeks) versus pre-term (less than 37 weeks) SEARCH STRATEGY: Searches were made
      of Medline from 1966 to December 2002, CINAHL (from 1982), Current Contents (from
      1988), EMBASE, and the Cochrane Controlled Trials Register (2002, issue 4).
      Bibliographies of conference proceedings were reviewed and unpublished studies
      were sought by hand searching the conference proceedings of the Society for
      Pediatric Research and the European Society for Pediatric Research from 1993 to
      2002. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of
      newborns, both pre-term and term, receiving epinephrine for unexpected apparent
      stillbirth or extreme bradycardia. DATA COLLECTION AND ANALYSIS: No studies were
      found meeting the criteria for inclusion in this review MAIN RESULTS: No studies
      were found meeting the criteria for inclusion in this review. REVIEWER'S
      CONCLUSIONS: We found no randomised, controlled trials evaluating the
      administration of epinephrine to the apparently stillborn or extremely
      bradycardic newborn infant. Similarly, we found no randomised, controlled trials
      which addressed the issues of optimum dosage and route of administration of
      epinephrine. Current recommendations for the use of epinephrine in newborn
      infants are based only on evidence derived from animal models and the human adult
      literature. Randomised trials in neonates are urgently required to determine the
      role of epinephrine in this population.

PMID- 12804492
TI  - Surgery versus medical therapy for heavy menstrual bleeding.
AB  - BACKGROUND: Heavy menstrual bleeding significantly impairs the quality of life of
      many otherwise healthy women. Perception of heavy bleeding is highly subjective
      and management of the condition usually depends upon the degree of bleeding and
      discomfort found acceptable by the individual woman. Medical treatment options
      include oral medications and a hormone-releasing intrauterine system (LNG-IUS).
      Surgical options include conservative surgery (uterine resection or ablation) and
      hysterectomy. OBJECTIVES: To compare the effectiveness, safety and acceptability
      of surgery versus medical therapy for heavy menstrual bleeding. SEARCH STRATEGY:
      We searched the Cochrane Menstrual Disorders and Subfertility Group trials
      register (October 2002), Cochrane Controlled Trials Register (Issue 3, 2002),
      MEDLINE (1966 to October 2002), EMBASE (1980 to October 2002), Current Contents
      (1993 to week 45, 2002), Biological Abstracts (1969 to September 2002), PsycINFO
      (1985 to October 2002), CINAHL (1982 to October 2002), and reference lists of
      articles. We also contacted pharmaceutical companies and experts in the field.
      SELECTION CRITERIA: Controlled randomised trials comparing surgery (conservative
      surgery and hysterectomy) versus medical therapy (both oral and intrauterine) for
      heavy menstrual bleeding DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trials for quality and extracted data, calculating odds
      ratios for dichotomous outcomes and weighted mean differences for continuous
      outcomes. MAIN RESULTS: Five trials met the inclusion criteria. They randomised
      625 women, 311 to receive surgery and 314 to receive medical treatment. One trial
      compared endometrial resection with oral medication: surgery proved significantly
      more effective in controlling bleeding (OR 10.62, 95% CI 5.30 to 21.27) and
      significantly less likely to cause side effects (OR 0.15, 95% CI 0.07 to 0.31).
      In the other four trials the medical arms received LNG-IUS and the surgical arms
      received conservative surgery or hysterectomy. At one year no statistically
      significant difference was shown between LNG-IUS and any surgical treatment in
      satisfaction rates or quality of life, though conservative surgery was
      significantly less likely to cause adverse effects (OR 0.24, 95% CI 0.11 to
      0.49). Although conservative surgery was significantly more effective than LNG
      IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38), a small
      trial showed no significant difference between the treatments at two and three
      years. Hysterectomy stopped all bleeding but caused serious complications for
      some women. REVIEWER'S CONCLUSIONS: Surgery reduces menstrual bleeding at one
      year more than medical treatments, but LNG-IUS appears equally beneficial in
      improving quality of life and may control bleeding as effectively as conservative
      surgery over the long term. Oral medication suits a minority of women long term.

PMID- 12804493
TI  - Enamel matrix derivative (Emdogain) for periodontal tissue regeneration in
      intrabony defects.
AB  - BACKGROUND: Periodontitis is a chronic infective disease of the gums caused by
      bacteria present in dental plaque. This condition induces the breakdown of the
      tooth supporting apparatus until teeth are lost. Surgery may be indicated to
      arrest disease progression and regenerate lost tissues. Several surgical
      techniques have been developed to regenerate periodontal tissues including guided
      tissue regeneration (GTR), bone grafting (BG) and the use of enamel matrix
      derivative (EMD). EMD is an extract of enamel matrix and contains amelogenins of
      various molecular weights. There is evidence to show that amelogenins are
      involved not only in enamel formation, but also in the formation of the
      periodontal attachment during tooth formation. OBJECTIVES: To test the efficacy
      of EMD in comparison with open flap debridement, GTR and various BG procedures
      for the treatment of intrabony defects. SEARCH STRATEGY: We searched the Cochrane
      Oral Health Group's Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE and EMBASE. Several journals were handsearched. No
      language restrictions were applied. Authors of randomised controlled trials
      (RCTs) identified, personal contacts and the manufacturer were contacted to
      identify unpublished trials. Most recent search: January 2003. SELECTION
      CRITERIA: RCTs on patients affected by periodontitis having intrabony defects
      treated with EMD compared with open flap debridement, GTR and various BG
      procedures with at least one year follow up. The outcome measures considered
      were: tooth loss, changes in probing attachment levels (PAL), pocket depths
      (PPD), gingival recessions (REC), marginal bone levels on intraoral radiographs
      and postoperative infections. DATA COLLECTION AND ANALYSIS: Screening of eligible
      studies, assessment of the methodological quality of the trials and data
      extraction were conducted in duplicate and independently by two reviewers.
      Results were expressed as random effect models using weighted mean differences
      for continuous outcomes and relative risk for dichotomous outcomes with 95%
      confidence interval (CI). Heterogeneity was investigated including both clinical
      and methodological factors. MAIN RESULTS: No difference in tooth loss was
      observed. A meta-analysis including eight trials showed that Emdogain treated
      sites displayed statistically significant PAL improvements (mean difference 1.3
      mm, 95%CI: 0.8 to 1.8) and PPD reduction (1 mm, 95%CI: 0.5 to 1.4) when compared
      to flap surgery. Comparing Emdogain with GTR (six trials), GTR showed a
      statistically significant reduction of PPD (0.6 mm) and increase of REC (0.5 mm).
      No difference in postoperative infections was observed. REVIEWER'S CONCLUSIONS:
      Emdogain is able to significantly improve PAL levels (1.3mm) and PPD reduction
      (1mm) when compared to flap surgery, however these results may not have a great
      clinical impact, since it has not been shown that more periodontally compromised
      teeth could be saved. There was no evidence of clinically important differences
      between GTR and Emdogain.

PMID- 12804494
TI  - Periurethral injection therapy for urinary incontinence in women.
AB  - BACKGROUND: Stress urinary incontinence is a common, troublesome symptom amongst
      adult women. Periurethral injection of bulking agents is a surgical procedure
      used for the treatment of urinary incontinence. OBJECTIVES: To assess the effects
      of periurethral injection therapy in the treatment of urinary incontinence in
      women. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials
      register (February 2003), MEDLINE (January 1996 to January 2003), PREMEDLINE (7
      February 2003) and the reference lists of relevant articles. Date of the most
      recent searches: February 2003. SELECTION CRITERIA: All randomised or quasi
      randomised controlled trials of treatment for urinary incontinence, in which at
      least one management arm involved periurethral injection therapy. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently assessed methodological quality of each
      study using explicit criteria. Data extraction was undertaken independently using
      a standard form and clarification concerning possible unreported data sought
      directly from the investigators. MAIN RESULTS: We identified seven trials that
      met the inclusion criteria. The limited data available prevented meta-analysis.
      Injection of autologous fat was compared to placebo in a study of 68 women which
      was terminated early because of safety concerns. No differences in subjective or
      objective outcome were found in the two groups. No studies were found comparing
      injection therapy with conservative treatment. The single study that compared
      injection with a variety of surgical management in 133 women found no significant
      difference in subjective outcome but did note significantly better objective
      outcome in the surgical group. The four studies that compared different agents
      found that silicone particles and carbon spheres gave improvement at 12 months
      equivalent to collagen. A comparison of paraurethral and transurethral methods of
      delivery of the bulking agent found similar outcome but a higher rate of early
      complications in the paraurethral group. REVIEWER'S CONCLUSIONS: Data from the
      available randomised trials suggest, but do not prove, that periurethral
      injection of established manufactured bulking agents results in subjective and
      objective short term improvement of symptomatic female stress urinary
      incontinence in adults. Future recommendation as a first line treatment would
      require evidence of patient benefit and cost-effectiveness from randomised trials
      involving placebo and conservative treatment arms. Future studies should also
      record long-term outcome and monitor for delayed particle migration. Injection
      therapy is probably inferior to surgery but a long term comparative study against
      a single standard procedure (Burch colposuspension) is required to prove this. It
      is recommended that phase III studies of newer agents will not be worthwhile
      until the aforementioned trials have been performed and a rationale for the use
      of injection therapy decided. For women with extensive co-morbidity precluding
      anaesthesia, injection therapy may represent a useful option for relief of
      symptoms for a 12 month period although 2 or 3 injections are likely to be
      required to achieve a satisfactory result.

PMID- 12804495
TI  - Reduction of the number of fetuses for women with triplet and higher order
      multiple pregnancies.
AB  - BACKGROUND: When couples are faced with the dilemma of a higher order multiple
      pregnancy there are three options. Termination of the entire pregnancy has
      generally not been acceptable to women, especially for those with a past history
      of infertility. Attempting to continue with all the fetuses is associated with
      inherent problems of preterm birth, survival and long term morbidity. The other
      alternative relates to reduction in the number of fetuses by selective
      termination. The acceptability of these options for the couple will depend on
      their social background and underlying beliefs. This review focused on reduction
      in the number of fetuses. OBJECTIVES: To assess a policy of multifetal reduction
      with a policy of expectant management of women with a triplet or higher order
      multiple pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (30 September 2002), the Cochrane Controlled
      Trials Register (The Cochrane Library, Issue 2, 2002), and PubMed (to 30
      September 2002). SELECTION CRITERIA: Randomized controlled trials with reported
      data that compared outcomes in mothers and babies who were managed expectantly
      with outcomes in women who underwent selective fetal reduction of a triplet or
      higher order multiple pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted data. MAIN RESULTS: There were
      no randomised controlled trials identified. REVIEWER'S CONCLUSIONS: There are
      insufficient data available to support a policy of pregnancy reduction procedures
      for women with a triplet or higher order multiple pregnancy. While randomised
      controlled trials will provide the most reliable evidence about the risks and
      benefits of fetal reduction procedures, reduction in the number of fetuses by
      selective termination may not been acceptable to women, especially for those with
      a past history of infertility. The acceptability of this option, and willingness
      to undergo randomisation will depend on the couple's social background and
      beliefs, and consequently, recruitment to such a trial may prove exceptionally
      difficult.

PMID- 12804496
TI  - Combination contraceptives: effects on weight.
AB  - BACKGROUND: Weight gain is often attributed as a side effect of combination
      hormonal contraceptive, and many women and clinicians believe that an association
      exists. Concern about weight gain can limit the use of this highly effective
      method of contraception by deterring the initiation of its use and causing early
      discontinuation among users. Nevertheless, a causal relationship between
      combination contraceptives and weight gain has not been established. OBJECTIVES:
      The aim of the review was to evaluate the association between combination
      contraceptive use and changes in weight. SEARCH STRATEGY: We searched the
      computerized databases MEDLINE, Popline, CENTRAL, EMBASE, and LILACS for studies
      of combination contraceptives. We also wrote to known investigators and
      manufacturers to request information about other published or unpublished trials
      not discovered in our search. SELECTION CRITERIA: All English-language,
      randomized controlled trials at least three treatment cycles in duration that
      compared a combination contraceptive to a placebo or with a combination
      contraceptive that differed in drug, dosage, regimen, and/or study length were
      eligible. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the
      literature searches were assessed. Data were entered and analyzed with RevMan
      4.1, and a second reviewer verified the data entered. Depending on the data
      available, the weighted mean difference using a fixed effects model with 95%
      confidence intervals was calculated for the mean change in weight between
      baseline and post-treatment measurements or the Peto odds ratio with 95%
      confidence intervals was calculated using the proportion of women who gained or
      lost more than a specified amount of weight. MAIN RESULTS: The three placebo
      controlled, randomized trials did not find evidence supporting a causal
      association between combination oral contraceptives or a combination skin patch
      and weight gain. Most comparisons of different combination contraceptives showed
      no substantial difference in weight. In addition, discontinuation of combination
      contraceptives because of weight gain did not differ between groups where this
      was studied. REVIEWER'S CONCLUSIONS: Available evidence is insufficient to
      determine the effect of combination contraceptives on weight, but no large effect
      is evident.

PMID- 12804497
TI  - Combined hormonal versus nonhormonal versus progestin-only contraception in
      lactation.
AB  - BACKGROUND: Contraception for women who are breastfeeding is a public health
      issue of global importance. Each year over 100 million women make decisions about
      beginning or resuming contraception after childbirth. These decisions include
      both the choice of contraceptive method and the time at which its use begins,
      both of which continue to be debated by experts. Choices of contraception may be
      limited for lactating women due to concerns about hormonal effects on quality and
      quantity of milk, passage of hormones to the infant, and infant growth. Ideally,
      the contraceptive method chosen should not interfere with lactation.
      Additionally, because the return of menstruation and ovulation can be
      unpredictable in breastfeeding women, the timing of contraception initiation is
      important. OBJECTIVES: To determine the effect of combined oral contraceptives
      and progestin-only contraceptives on lactation. The a priori hypothesis is that
      combined oral contraception impairs lactation, making it less appropriate than
      progestin-only or nonhormonal contraception for breastfeeding women. SEARCH
      STRATEGY: We used PUBMED, POPLINE, EMBASE, LILACS, and Cochrane Controlled Trials
      Register computer searches, supplemented by review articles and contact with
      investigators. SELECTION CRITERIA: We sought all randomized controlled trials,
      reported in any language, that included any form of hormonal contraception
      compared with another form of hormonal contraception, nonhormonal contraception,
      or placebo during lactation. Hormonal contraception could include combined oral
      or injectable contraceptives, progestin-only oral or injectable contraceptives,
      hormonal implants, or hormonal intrauterine devices. Study participants included
      breastfeeding women of any age or parity who desired contraception. DATA
      COLLECTION AND ANALYSIS: We evaluated the methodological quality of each report
      and sought to identify duplicate reporting of data from multicenter trials. We
      abstracted data onto data collection forms. Principal outcome measures included
      quantity of milk; biochemical analysis of milk composition; initiation,
      maintenance and duration of lactation; infant growth; efficacy of contraceptive
      method while breastfeeding; and timing of contraception initiation and its
      effects on lactation. Because the trials did not have uniform interventions,
      often lacked quantifiable outcomes, and had poor methodological quality, we could
      not aggregate the data in a meta-analyses. MAIN RESULTS: Seven reports from five
      randomized controlled trials met our inclusion criteria. Most of the five trials
      did not specify their method used to generate a random sequence, method of
      allocation concealment, blinding of treatments, or use of an intention-to-treat
      analysis. Additionally, high loss to follow-up rates invalidated at least two
      studies. The findings from two reports comparing oral contraceptives to placebo
      during lactation were conflicting. Another trial found no inhibitory effects on
      lactation from progestin-only contraceptives. Finally, the WHO trial found no
      effect of progestin-only contraceptives on lactation but a decline in breast milk
      volume from combination contraceptives during lactation. High loss to follow-up
      rates, however, undermine the credibility of the WHO trial. No significant
      differences in infant growth or weight appeared in any of the included trials as
      a result of the use of hormonal contraception during lactation. REVIEWER'S
      CONCLUSIONS: Evidence from randomized controlled trials on the effect of hormonal
      contraceptives during lactation is limited and of poor quality; results should be
      interpreted with caution. The existing randomized controlled trials are
      insufficient to establish an effect of hormonal contraception, if any, on milk
      quality and quantity. Evidence is inadequate to make recommendations regarding
      hormonal contraceptive use for lactating women. At least one properly conducted
      randomized controlled trial of adequate size is urgently needed to address this
      question.

PMID- 12804498
TI  - Ibuprofen for Alzheimer's disease.
AB  - BACKGROUND: Non-steroidal antiinflammatory drugs such as ibuprofen may have a
      role in the treatment of conditions characterized by inflammatory processes.
      Ibuprofen may attenuate the effects of modulators of inflammation that have been
      implicated in the pathogenesis of Alzheimer's disease. OBJECTIVES: To investigate
      the efficacy of ibuprofen treatment for people with Alzheimer's disease. SEARCH
      STRATEGY: The trials were identified from a search of the Specialized Register of
      the Cochrane Dementia and Cognitive Improvement Group on 10 December 2002 using
      the (many) terms listed in the main text of the review. The CDCIG Register is
      updated regularly and contains records from all major health care databases and
      many ongoing trials databases. In addition computerized databases and Internet
      sites pertaining to ibuprofen and Alzheimer's disease were systematically
      examined by two reviewers independently. Data on ongoing trials of ibuprofen for
      the treatment of people with AD were also sought. SELECTION CRITERIA: Eligibility
      for this review included all single or multi centre placebo-controlled randomized
      trials examining the efficacy of ibuprofen in the treatment of people diagnosed
      with Alzheimer's disease according to internationally accepted criteria.
      Inclusion and exclusion criteria were specified to ensure lack of bias in
      selection and methodological quality of selected trials. DATA COLLECTION AND
      ANALYSIS: The aim was for the two reviewers NT and HF to collect data
      independently. The data selected would reflect cognitive, behavioural, physical
      and psychological domains of AD. MAIN RESULTS: A systematic search of all
      available databases and other sources failed to identify any completed
      randomized, double-blind and placebo-controlled trials, assessing the efficacy of
      ibuprofen in AD eligible for inclusion in the review. One double-blind placebo
      controlled trial investigating ibuprofen treatment for age-associated memory
      impairment has been identified, but is yet unfinished and no data are yet
      available. Other trials assessing the effect of ibuprofen on CSF beta amyloid in
      cognitively unimpaired individuals and the effect of other NSAIDs such as
      naproxen and rofecoxib for people with AD are currently under way. REVIEWER'S
      CONCLUSIONS: No evidence yet exists from randomized double-blind and placebo
      controlled trials on whether ibuprofen is efficacious for patients diagnosed as
      having Alzheimer's disease. Ibuprofen, like other NSAIDs, has an identifiable and
      in some instances a significant side-effect profile which may include
      gastrointestinal bleeding. Therefore, it needs to be shown that the benefits of
      such a treatment outweighs the risk of side effects before ibuprofen can be
      recommended for people with Alzheimer's disease.

PMID- 12804499
TI  - Antipsychotic drug treatment for elderly people with late-onset schizophrenia.
AB  - BACKGROUND: At least 0.1% of the world's elderly population have a diagnosis of
      schizophrenia that started late in life and prognosis may be made worse by delay
      and avoidance of treatment. OBJECTIVES: To assess the effects of antipsychotic
      drugs for elderly people with late-onset schizophrenia. SEARCH STRATEGY: We
      searched the Cochrane Schizophrenia Group trials register (September 2002). This
      register is compiled by methodical searches of BIOSIS, Cochrane Central Register
      of Controlled Trials (CENTRAL), CINAHL, Dissertation Abstracts, EMBASE, LILACS,
      MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching
      of relevant journals and numerous conference proceedings. References of all
      identified studies were also inspected for more trials. SELECTION CRITERIA: All
      relevant randomised controlled trials that compared atypical antipsychotic drugs
      with other treatments for elderly people (at least 80% of whom should be over 65
      years of age) with a recent (within five years) diagnosis of schizophrenia or
      schizophrenia like illnesses such as delusional disorder, schizoaffective
      disorder, schizophreniform psychosis or paraphrenia. DATA COLLECTION AND
      ANALYSIS: All citations were inspected by the principal reviewer (SA) and papers
      ordered and re-inspected (by IA, NAQ, SP) to ensure reliable selection.
      Methodological quality of trials would have been assessed using the Cochrane
      Reviewers' Handbook criteria and data would have been independently extracted.
      Data were to have been excluded if loss to follow up was greater than 50%. For
      homogeneous dichotomous data the relative risk (RR), 95% confidence interval
      (CI), and the number needed to treat (NNT) and number needed to harm (NNH), were
      to have been calculated based on an intention-to-treat basis. MAIN RESULTS:
      Electronic searching produced 119 references, 65 of which were selected for
      examination of the full text. These referred to 38 studies. Not one study met the
      entry criteria for this review. Most were randomised but involved elderly people
      with chronic schizophrenia. Four trials involved people with schizophrenia, and
      did include a minority who suffered from paraphrenia. Outcomes for this sub
      group, however, were not reported. One randomised study (n=18) did focus on late
      onset schizophrenia, but unfortunately the two treatments under evaluation,
      remoxipride and thioridazine, have both been withdrawn from use. REVIEWER'S
      CONCLUSIONS: There is no trial-based evidence upon which to base guidelines for
      the treatment of late onset schizophrenia. This review highlights the need for
      good quality controlled clinical trials to address the effects of antipsychotic
      drugs for this group. Such trials are possible. Until they are undertaken people
      with late onset schizophrenia will be treated by doctors using clinical judgement
      and habit to guide prescribing.

PMID- 12804500
TI  - Screening children in the first four years of life to undergo early treatment for
      otitis media with effusion.
AB  - BACKGROUND: Otitis media with effusion (OME) is the most common cause of acquired
      hearing loss in childhood and has been associated with delayed language
      development and behavioural problems. This condition has a prevalence of about
      20% at the age of two years, a time of rapid language development. It is most
      often asymptomatic. Effective treatment exists for clearing effusions. Some have
      argued, therefore, that children should be screened and treated early if found to
      have clinically important OME. However, there is a high rate of spontaneous
      resolution of effusions and for some children, effusions may represent a
      physiological response that does not reduce hearing significantly or impact
      negatively on language development or behaviour. Previous reviews of the effect
      of screening and treatment have included studies using non-randomised designs.
      OBJECTIVES: The aim of this review was to assess evidence from randomised
      controlled trials about the effectiveness, on language and behavioural outcomes,
      of screening and treating children with clinically important OME in the first
      four years of their life. The focus was on the first four years of life because
      this is the time of most rapid language development. The consequences of hearing
      loss are likely to be most serious during this time. In addition, children of
      this age are least likely to be able to report or seek help for impaired hearing,
      particularly if these problems have a slow onset and are subtle. SEARCH STRATEGY:
      We searched the Cochrane Controlled Trials Register (the Cochrane Library Issue
      1, 2002), MEDLINE (1966-2002) and EMBASE (1974-2002) (all in February 2002) and
      reference lists of all studies. We also contacted the first authors of the
      studies we included in this review. SELECTION CRITERIA: 1. Randomised controlled
      trials evaluating interventions for OME among children with OME identified
      through screening. 2. Comparison of outcomes for children randomised to be
      screened for OME and outcomes for children who were not randomised to be screened
      for OME. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data
      and assessed trial quality. MAIN RESULTS: We identified no trials comparing
      outcomes for children randomised to be screened for OME with outcomes for
      children who were not randomised to be screened for OME. We identified three
      trials evaluating interventions for OME among children with OME identified
      through screening. From these trials, we found no evidence of clinically
      important benefit in language development from screening and treating children
      with clinically important OME. Although there was a beneficial effect on the
      resolution of OME and improved hearing in the short-term (six months), this
      effect largely disappeared in the long-term (12 months). REVIEWER'S CONCLUSIONS:
      The identified randomised trials do not show an important benefit from screening
      of the general population of asymptomatic children in the first four years of
      life for OME on language development and behaviour.

PMID- 12804502
TI  - Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood
      transfusion.
AB  - BACKGROUND: Concerns regarding the safety of transfused blood have generated
      considerable enthusiasm for the use of technologies intended to reduce the use of
      allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis
      (PRP) offers an alternative approach to blood conservation. OBJECTIVES: To
      examine the evidence for the efficacy of PRP in reducing peri-operative
      allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on
      clinical outcomes such as mortality and re-operation rates. SEARCH STRATEGY:
      Studies were identified by: computer searches of MEDLINE, EMBASE, Current
      Contents, and the Cochrane Library (to June 2001). These searches were
      supplemented by checking the reference lists of published articles, reports, and
      reviews. SELECTION CRITERIA: Controlled parallel group trials in which adult
      patients, scheduled for non-urgent surgery, were randomised to PRP, or to a
      control group who did not receive the intervention. DATA COLLECTION AND ANALYSIS:
      Main outcomes measured were: the number of patients receiving an allogeneic RBC
      transfusion, and the amount of RBC transfused. Trial quality was assessed using
      criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al. (Jadad 1996).
      MAIN RESULTS: Nineteen trials of PRP were identified that reported data for the
      number of patients exposed to allogeneic RBC transfusion. These trials evaluated
      a total of 1452 patients. The pooled relative risk (RR) of exposure to allogeneic
      blood transfusion in those patients randomised to PRP was 0.71 (95%CI: 0.56,
      0.90), equating to a relative risk reduction (RRR) of 29%; the average absolute
      risk reduction (ARR) was 19% (RD = -0.19: 95%CI: -0.29, -0.09). On average, PRP
      did not significantly reduce the total volume of RBC transfused (weighted mean
      difference [WMD] = -0.69: 95%CI: -1.93, 0.56 units). Substantial statistical
      heterogeneity was observed (p < 0.001). Trials provided inadequate data regarding
      the impact of PRP on morbidity, mortality, and hospital length of stay. The
      majority of trials were small and of poor methodological quality. REVIEWER'S
      CONCLUSIONS: Although the results suggest that PRP is effective in reducing
      allogeneic RBC transfusion in adult patients undergoing elective surgery, there
      was considerable heterogeneity in treatment effects and the trials were of poor
      methodological quality. As the majority of trials were unblinded, transfusion
      practices may have been influenced by knowledge of the patient's allocation
      status, potentially exaggerating the true magnitude of the beneficial effect of
      PRP. The available studies provided inadequate data for firm conclusions to be
      drawn regarding the impact of PRP on clinically important endpoints.

PMID- 12804501
TI  - Fibrin sealant use for minimising peri-operative allogeneic blood transfusion.
AB  - BACKGROUND: Fibrin sealants have gained increasing popularity as interventions to
      improve peri-operative (intra/post-operative) haemostasis and diminish the need
      for allogeneic red cell transfusion (blood from an unrelated donor). OBJECTIVES:
      To examine the efficacy of fibrin sealants in reducing peri-operative blood loss
      and allogeneic red blood cell (RBC) transfusion. SEARCH STRATEGY: Studies were
      identified by: searches of MEDLINE, EMBASE, Current Contents, the Cochrane
      Library (July 2002), manufacturer web sites (to July 2002), and bibliographies of
      published articles. SELECTION CRITERIA: Controlled trials in which adult
      patients, scheduled for elective surgery, were randomised to fibrin sealant
      treatment or to a control group who did not receive fibrin sealant treatment.
      Trials were eligible if they reported data on the number of patients exposed to
      allogeneic red cell transfusion, the volume of blood transfused, or blood loss
      (assessed objectively). DATA COLLECTION AND ANALYSIS: Primary outcomes measured
      were: the number of patients exposed to allogeneic red cells, the amount of blood
      transfused, and blood loss. Other outcomes measured were: re-operation due to
      bleeding, infection, mortality, and length of hospital stay. Treatment effects
      were pooled using a random effects model. MAIN RESULTS: Seven trials, including a
      total of 388 patients, reported data on peri-operative exposure to allogeneic RBC
      transfusion. Fibrin sealant treatment, on average, reduced the rate of exposure
      to allogeneic red cell transfusion by a relative 54% (relative risk [RR] = 0.46:
      95%CI = 0.32 to 0.68). Eight trials, including a total of 442 patients, provided
      data for post-operative blood loss. Fibrin sealant treatment reduced blood loss
      on average by around 134 per patient (95%CI = 51 to 217 ). However the trials
      reviewed were small and of poor methodological quality (91% unblinded).
      REVIEWER'S CONCLUSIONS: Overall the results suggest that fibrin sealants are
      efficacious in reducing both post-operative blood loss and peri-operative
      exposure to allogeneic RBC transfusion. However, due to the lack of blinding,
      transfusion practices may have been influenced by knowledge of the patient's
      treatment status. This raises concerns about the use of blood transfusion
      practice as an outcome variable in trials of fibrin sealant. In the case of blood
      loss, the results must be interpreted with caution, in view of the statistically
      significant heterogeneity in treatment effect observed. Large, methodologically
      rigorous, randomised controlled trials of fibrin sealants are needed.

PMID- 12804503
TI  - Amitriptyline versus other types of pharmacotherapy for depression.
AB  - BACKGROUND: For many years amitriptyline has been considered one of the reference
      compounds for the pharmacological treatment of depression. However, new tricyclic
      drugs, heterocyclic compounds and the selective serotonin reuptake inhibitors
      have been introduced on the market with the claim of a more favourable
      tolerability/efficacy profile. OBJECTIVES: The aim of the present systematic
      review was to investigate the tolerability and efficacy of amitriptyline in
      comparison with the other tricyclic/heterocyclic antidepressants and with the
      selective serotonin reuptake inhibitors. SEARCH STRATEGY: The Cochrane
      Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (2002
      3) and the Cochrane Central Register of Controlled Trials (CENTRAL) were
      searched. Key journals and conference abstracts were handsearched. Pharmaceutical
      companies were contacted for information on unpublished materials. SELECTION
      CRITERIA: Only randomised controlled trials were included. Study participants
      were of either sex and any age with a primary diagnosis of depression. Included
      trials compared amitriptyline with another tricyclic/heterocyclic antidepressant
      or with one of the selective serotonin reuptake inhibitors. DATA COLLECTION AND
      ANALYSIS: Data were extracted using a standardised form. The number of patients
      undergoing the randomisation procedure, the number of patients who completed the
      study and the number of improved patients were extracted. In addition, group mean
      scores at the end of the trial on Hamilton Depression Scale or any other
      depression scale were extracted. In the tolerability analysis, the number of
      patients failing to complete the study and the number of patients complaining of
      side-effects was extracted. MAIN RESULTS: The estimate of the overall odds ratio
      for responders showed that more subjects responded to amitriptyline in comparison
      with the control antidepressant group (odds ratio 1.12, 95% confidence interval
      1.01, 1.23, number needed to treat 50). The estimate of the efficacy of
      amitriptyline and control agents on a continuous outcome revealed an effect size
      which also significantly favoured amitriptyline (Standardised Mean Difference
      0.13, 95% confidence interval 0.04, 0.23). Whilst these differences are
      statistically significant, their clinical significance is less clear. When the
      efficacy analysis was stratified by drug class, no difference in outcome emerged
      between amitriptyline and either tricyclic or selective serotonin reuptake
      inhibitor comparators. The dropout rate in patients taking amitriptyline and
      control agents was similar; however, the estimate of the proportion of patients
      who experienced side-effects significantly favoured control agents in comparison
      with amitriptyline (odds ratio 0.63, 95% confidence interval 0.56, 0.71). When
      the tolerability analysis was stratified by drug class, the dropout rate in
      patients taking amitriptyline and the selective serotonin reuptake inhibitors
      significantly favoured the latter (odds ratio 0.84, 95% confidence interval
      0.75,0.95, number needed to harm 40). When the responder analysis was stratified
      by study setting amitriptyline was more effective than control ADs in inpatients
      (odds ratio 1.22, 95% confidence interval 1.04, 1.42, number needed to treat 24),
      but not in outpatients (odds ratio 1.01, 95% confidence interval 0.88, 1.17,
      number needed to treat = 200). REVIEWER'S CONCLUSIONS: This present systematic
      review indicates that amitriptyline is at least as efficacious as other
      tricyclics or newer compounds. However, the burden of side-effects in patients
      receiving it was greater. In comparison with the selective serotonin reuptake
      inhibitors amitriptyline was less well tolerated, and although counterbalanced by
      a higher proportion of responders, the difference was not statistically
      significant.

PMID- 12804504
TI  - Metalloporphyrins for treatment of unconjugated hyperbilirubinemia in neonates.
AB  - BACKGROUND: Metalloporphyrins are heme analogues that inhibit heme oxygenase, the
      rate-limiting enzyme in the catabolism of heme to bilirubin. By preventing the
      formation of bilirubin, they have the potential to reduce the level of
      unconjugated bilirubin in neonates and thereby reduce the risk of neonatal
      encephalopathy and long term neurodevelopmental impairment from bilirubin
      toxicity to the nervous system. OBJECTIVES: 1. To determine the efficacy of
      metalloporphyrins in reducing bilirubin levels, reducing the need for
      phototherapy or exchange transfusion and reducing the incidence of bilirubin
      encephalopathy in neonates with unconjugated hyperbilirubinemia when compared to
      placebo, phototherapy or exchange transfusion. 2. To determine the nature and
      frequency of side effects of metalloporphyrins when used to treat unconjugated
      hyperbilirubinemia in neonates. SEARCH STRATEGY: We searched Medline (1966 -
      January 2003) and the Cochrane Controlled Trials Register (CCTR) from the
      Cochrane Library (2003, issue 1). We hand-searched the articles cited in each
      publication obtained. We hand searched the abstracts of the Society for Pediatric
      Research (USA) (published in Pediatric Research) for the years 1985 - 2002.
      SELECTION CRITERIA: We included only randomized controlled studies, in which
      preterm or term neonates (age 28 days of life or less) with unconjugated
      hyperbilirubinemia due to any cause were randomly allocated to receive a
      metalloporphyrin in the treatment arm(s), and to receive a placebo or a
      conventional treatment (phototherapy or exchange transfusion) or no treatment for
      hyperbilirubinemia in the comparison arm(s). Any preparation of metalloporphyrin
      could be used, in any form, by any route, at any dose. DATA COLLECTION AND
      ANALYSIS: Two authors extracted data independently. Data were entered into Revman
      by one author and checked by a second author. Prespecified subgroup analyses were
      planned in term versus preterm infants, hemolytic versus non-hemolytic causes of
      jaundice and according to the type of metalloporphyrin used. MAIN RESULTS: Three
      small studies, enrolling a total of 170 infants, were eligible for inclusion in
      this review. None blinded intervention or outcome assessment. In all three
      studies some patients were excluded after randomization. Metalloporphyrin-treated
      infants appeared to have short-term benefits compared to controls, including a
      lower maximum plasma bilirubin level in one study, a lower frequency of severe
      hyperbilirubinemia in one study, a decreased need for phototherapy, fewer plasma
      bilirubin measurements and a shorter duration of hospitalization. None of the
      enrolled infants required an exchange transfusion in the two studies that
      described this outcome. None of the studies reported on neonatal kernicterus,
      death, long-term neurodevelopmental outcomes or iron deficiency anemia. Though a
      small number of metalloporphyrin-treated as well as control infants developed a
      photosensitivity rash, the trials were too small to rule out an increase in the
      risk of photosensitivity or other adverse effects from metalloporphyrin
      treatment. No subgroup analyses were possible due to the small number of included
      trials. REVIEWER'S CONCLUSIONS: Treatment of neonatal unconjugated
      hyperbilirubinemia with metalloporphyrins may reduce neonatal bilirubin levels
      and decrease the need for phototherapy and hospitalization. There is no evidence
      to support or refute the possibility that treatment with a metalloporphyrin
      decreases the risk of neonatal kernicterus or of long-term neurodevelopmental
      impairment due to bilirubin encephalopathy. There is no evidence to support or
      refute the possibility that cutaneous photosensitivity is increased with
      metalloporphyrin treatment. Routine treatment of neonatal unconjugated
      hyperbilirubinemia with a metalloporphyrin cannot be recommended at present.

PMID- 12804505
TI  - Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low
      birth weight infants.
AB  - BACKGROUND: A patent ductus arteriosus (PDA) often complicates the clinical
      course of preterm infants and increases the risk of intraventricular hemorrhage
      (IVH), necrotizing enterocolitis (NEC), chronic lung disease (CLD) and death. The
      standard treatment to close a PDA is indomethacin. Its use is associated with
      renal, gastrointestinal and cerebral side-effects. Ibuprofen has been shown to be
      effective in closing a PDA without reducing blood flow velocity to the brain, gut
      or kidneys. OBJECTIVES: To determine the effectiveness and safety of prophylactic
      ibuprofen compared to placebo/no intervention or other cyclo-oxygenase inhibitor
      drugs (indomethacin, mefenamic acid, etc) in the prevention of PDA in preterm
      infants. SEARCH STRATEGY: Randomized controlled trials comparing prophylactic
      ibuprofen use with placebo/no intervention/indomethacin were identified by
      searching the Cochrane Controlled Trial Register (The Cochrane Library, Issue 4,
      2002), MEDLINE (1966-November 2002), CINAHL (1982-November 2002), EMBASE (1980
      November 2002), reference lists of published trials and abstracts published in
      Pediatric Research (1990-2002). No language restrictions were applied. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials comparing use of
      ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs
      (indomethacin, mefenamic acid, etc) for the prevention of PDA in preterm and/or
      low birth weight infants. DATA COLLECTION AND ANALYSIS: Data regarding the
      clinical outcomes including presence of PDA on day three and day seven, need for
      surgical ligation, need for rescue treatment with cyclo-oxygenase inhibitors,
      IVH, mortality, renal and gastrointestinal complications were extracted. Meta
      analyses were performed using RevMan 4.1 and treatment estimates were reported as
      weighted mean difference (WMD), typical relative risk (RR), typical risk
      difference (RD) and, if statistically significant, number needed to treat (NNT)
      or number needed to harm (NNH), along with their 95% confidence intervals (CI).
      MAIN RESULTS: Four trials (n = 623) were included in the review. There was a
      statistically significant decrease in the incidence of PDA on day three in the
      ibuprofen group [typical RR 0.36 (95% CI 0.26, 0.49); typical RD -0.29 (95% CI 
      0.37, -0.21); NNT 3 (95% CI 3, 5); 3 trials, n = 488]. There was a significant
      increase in the serum creatinine levels in the ibuprofen group [WMD 0.11 mg/dl
      (95% CI 0.06, 0.17); 2 trials, n = 438]. There were no statistically significant
      differences in mortality, grade 3 or 4 IVH, CLD at 28 days or 36 weeks, need for
      surgical closure of PDA, NEC, GI hemorrhage, time to reach full feeds and urine
      output. One trial (Gournay 2002) (n = 135) reported on three infants in the
      ibuprofen group who developed pulmonary hypertension responsive to nitric oxide
      treatment. REVIEWER'S CONCLUSIONS: Prophylactic use of ibuprofen reduces the
      incidence of PDA. However, further trials, which address potential adverse
      effects including pulmonary hypertension, are needed. Such trials should include
      long-term neurodevelopmental outcomes. Trials comparing the effectiveness of
      prophylactic use of indomethacin versus ibuprofen may be warranted with
      particular reference to IVH, need for surgical ligation and neurodevelopmental
      outcome.

PMID- 12804506
TI  - Single dose oral celecoxib for postoperative pain.
AB  - BACKGROUND: Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor
      prescribed for the relief of chronic pain in osteoarthritis and rheumatoid
      arthritis. The drug is believed to be associated with fewer adverse effects than
      conventional non-steroidal anti-inflammatory drugs (NSAIDs). However, the
      effectiveness of celecoxib in the treatment of acute pain has not yet been
      assessed by systematic review. OBJECTIVES: To assess the analgesic efficacy and
      adverse effects of a single oral dose of celecoxib for moderate to severe
      postoperative pain. SEARCH STRATEGY: We searched the Cochrane Library Controlled
      Trials Register, MEDLINE, Biological Abstracts, PubMed and the Oxford Pain
      database. Date of the most recent search: May 2002. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of adults prescribed any dose of oral
      celecoxib or placebo for acute postoperative pain were included. DATA COLLECTION
      AND ANALYSIS: Two trials (418 subjects) met the inclusion criteria for this
      review. The trials were assessed for quality and the data extracted by two
      independent reviewers. Summed pain relief (TOTPAR) or pain intensity difference
      (SPID) was extracted and converted into dichotomous information yielding the
      number of patients with at least 50% pain relief over 4-6 hours. These derived
      results were used to calculate the relative benefit (RB) and number-needed-to
      treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS:
      The number-needed-to-treat for celecoxib 200 mg compared with placebo was 4.5 (CI
      3.3 to 7.2). For every 4.5 patients experiencing moderate to severe acute pain
      treated with celecoxib 200 mg one more will experience at least 50% pain relief
      that would not have done had they received placebo. The median time to
      remedication over 24 hours was 5.1 hours with celecoxib 200 mg and 1.5 hours with
      placebo. Quantitative analysis of adverse effects was not possible but no serious
      or unexpected adverse effects were reported. REVIEWER'S CONCLUSIONS: Single dose
      oral celecoxib is an effective means of postoperative pain relief, similar in
      efficacy to aspirin 600/650 mg, and paracetamol 1000 mg. The two trials included
      used celecoxib 200 mg, a dose 50% less than is recommended for acute pain. More
      trials are needed to estimate efficacy for recommended dose of 400 mg, and to
      reinforce current findings for 200 mg, and provide data for pooled quantitative
      estimates of adverse effects.

PMID- 12804507
TI  - Muscle relaxants for non-specific low back pain.
AB  - BACKGROUND: The use of muscle relaxants in the management of non-specific low
      back pain is controversial. It is not clear if they are effective, and concerns
      have been raised about the potential adverse effects involved. OBJECTIVES: The
      aim of this review was to determine if muscle relaxants are effective in the
      treatment of non-specific low back pain. SEARCH STRATEGY: A computer-assisted
      search of the Cochrane Library (Issue 2, 2002), MEDLINE (1966 up to October 2001)
      and EMBASE (1988 up to October 2001) was carried out. These databases were
      searched using the algorithm recommended by the Cochrane Back Review Group.
      References cited in the identified articles and other relevant literature were
      screened. SELECTION CRITERIA: Randomised and/or double-blinded controlled trials,
      involving patients diagnosed with non-specific low back pain, treated with muscle
      relaxants as monotherapy or in combination with other therapeutic modalities,
      were included for review. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently carried out the methodological quality assessment and data
      extraction of the trials. The analysis comprised not only a quantitative analysis
      (statistical pooling) but also a qualitative analysis ("best evidence
      synthesis"). This involved the appraisal of the strength of evidence for various
      conclusions using a rating system based on the quality and outcomes of the
      studies included. Evidence was classified as "strong", "moderate", "limited",
      "conflicting" or "no" evidence. MAIN RESULTS: Thirty trials met the inclusion
      criteria. Twenty-three trials (77%) were of high quality, 24 trials (80%) were on
      acute low back pain. Four trials studied benzodiazepines, 11 non-benzodiazepines
      and two antispasticity muscle relaxants in comparison with placebo. Results
      showed that there is strong evidence that any of these muscle relaxants are more
      effective than placebo for patients with acute LBP on short-term pain relief. The
      pooled RR for non-benzodiazepines versus placebo after two to four days was 0.80
      [95% CI; 0.71 to 0.89] for pain relief and 0.49 [95% CI; 0.25 to 0.95] for global
      efficacy. Adverse events, however, with a relative risk of 1.50 [95% CI; 1.14 to
      1.98] were significantly more prevalent in patients receiving muscle relaxants
      and especially the central nervous system adverse effects (RR 2.04; 95% CI; 1.23
      to 3.37). The various muscle relaxants were found to be similar in performance.
      REVIEWER'S CONCLUSIONS: Muscle relaxants are effective in the management of non
      specific low back pain, but the adverse effects require that they be used with
      caution. Trials are needed that evaluate if muscle relaxants are more effective
      than analgesics or non-steroidal anti-inflammatory drugs.

PMID- 12804508
TI  - Acetaminophen for osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published
      guidelines and expert opinion are divided over the relative role of acetaminophen
      (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs
      (NSAIDs) as first-line pharmacologic therapy. The comparative safety of
      acetaminophen and NSAIDs is important to consider as NSAIDs have the potential
      for serious gastrointestinal, renal, and cardiovascular toxicities, and
      acetaminophen in high dosages (greater than or equal to 2 grams per day), may
      also have the potential for serious upper gastrointestinal toxicity. OBJECTIVES:
      To assess the efficacy and safety of acetaminophen versus placebo and versus
      NSAIDs (ibuprofen, arthrotec, celecoxib,naproxen, rofecoxib) for treating OA.
      SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Issue 3,
      2002), MEDLINE (up to July 2002), and Current Contents (up to March 2002).
      Reference lists of identified RCTs and pertinent review articles were also hand
      searched. SELECTION CRITERIA: Published randomized controlled trials (RCTs)
      evaluating the efficacy and safety of acetaminophen alone in OA were considered
      for inclusion. DATA COLLECTION AND ANALYSIS: Pain, physical function and global
      assessment outcomes were reported. Results for continuous outcome measures were
      expressed as standardized mean differences. Dichotomous outcome measures were
      pooled using relative risk and the number needed to treat was calculated. MAIN
      RESULTS: Six RCTs and 1689 participants were included in the review. One study
      compared acetaminophen to placebo, and five compared acetaminophen to NSAIDs. In
      the placebo-controlled RCT, acetaminophen was shown to be clearly superior to
      placebo with a similar safety profile. The number needed to treat to achieve an
      improvement in pain was three. In the comparator-controlled RCTs, acetaminophen
      was less effective overall than NSAIDs in terms of pain reduction and global
      assessments but both drugs had similar efficacy in terms of improvements in
      functional status. No significant difference was found between the safety of
      acetaminophen and NSAIDs, although patients taking NSAIDS were more likely to
      withdraw due to GI events. REVIEWER'S CONCLUSIONS: The evidence to date suggests
      that NSAIDs are superior to acetaminophen for improving knee and hip pain in
      people with OA but have not been shown to be superior in improving function. The
      size of the treatment effect was modest, and the mean trial duration was only six
      weeks, therefore, additional considerations need to be factored in when making
      the decision between using acetaminophen or NSAIDs. In OA subjects with moderate
      to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.

PMID- 12804509
TI  - Physiotherapy interventions for shoulder pain.
AB  - BACKGROUND: The prevalence of shoulder disorders has been reported to range from
      seven to 36% of the population (Lundberg 1969) accounting for 1.2% of all General
      Practitioner encounters in Australia (Bridges Webb 1992). Substantial disability
      and significant morbidity can result from shoulder disorders. While many
      treatments have been employed in the treatment of shoulder disorders, few have
      been proven in randomised controlled trials. Physiotherapy is often the first
      line of management for shoulder pain and to date its efficacy has not been
      established. This review is one in a series of reviews of varying interventions
      for shoulder disorders, updated from an earlier Cochrane review of all
      interventions for shoulder disorder. OBJECTIVES: To determine the efficacy of
      physiotherapy interventions for disorders resulting in pain, stiffness and/or
      disability of the shoulder. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane
      Clinical Trials Regiter and CINAHL were searched 1966 to June 2002. The Cochrane
      Musculoskeletal Review Group's search strategy was used and key words gained from
      previous reviews and all relevant articles were used as text terms in the search.
      SELECTION CRITERIA: Each identified study was assessed for possible inclusion by
      two independent reviewers. The determinants for inclusion were that the trial be
      of an intervention generally delivered by a physiotherapist, that treatment
      allocation was randomised; and that the study population be suffering from a
      shoulder disorder, excluding trauma and systemic inflammatory diseases such as
      rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of
      the included trials was assessed by two independent reviewers according to a list
      of predetermined criteria, which were based on the PEDro scale specifically
      designed for the assessment of validity of trials of physiotherapy interventions.
      Outcome data was extracted and entered into Revman 4.1. Means and standard
      deviations for continuous outcomes and number of events for binary outcomes were
      extracted where available from the published reports. All standard errors of the
      mean were converted to standard deviation. For trials where the required data was
      not reported or not able to be calculated, further details were requested from
      first authors. If no further details were provided, the trial was included in the
      review and fully described, but not included in the meta-analysis. Results were
      presented for each diagnostic sub group (rotator cuff disease, adhesive
      capsulitis, anterior instability etc) and, where possible, combined in meta
      analysis to give a treatment effect across all trials. MAIN RESULTS: Twenty six
      trials met inclusion criteria. Methodological quality was variable and trial
      populations were generally small (median sample size = 48, range 14 to 180).
      Exercise was demonstrated to be effective in terms of short term recovery in
      rotator cuff disease (RR 7.74 (1.97, 30.32), and longer term benefit with respect
      to function (RR 2.45 (1.24, 4.86). Combining mobilisation with exercise resulted
      in additional benefit when compared to exercise alone for rotator cuff disease.
      Laser therapy was demonstrated to be more effective than placebo (RR 3.71 (1.89,
      7.28) for adhesive capsulitis but not for rotator cuff tendinitis. Both
      ultrasound and pulsed electromagnetic field therapy resulted in improvement
      compared to placebo in pain in calcific tendinitis (RR 1.81 (1.26, 2.60) and RR
      19 (1.16, 12.43) respectively). There is no evidence of the effect of ultrasound
      in shoulder pain (mixed diagnosis), adhesive capsulitis or rotator cuff
      tendinitis. When compared to exercises, ultrasound is of no additional benefit
      over and above exercise alone. There is some evidence that for rotator cuff
      disease, corticosteroid injections are superior to physiotherapy and no evidence
      that physiotherapy alone is of benefit for Adhesive Capsulitis REVIEWER'S
      CONCLUSIONS: The small sample sizes, variable methodological quality and
      heterogeneity in terms of population studied, physiotherapy intervention employed
      and length of follow up of randomised controlled trials of physiotherapy
      interventions results in little overall evidence to guide treatment. There is
      evidence to support the use of some interventions in specific and circumscribed
      cases. There is a need for trials of physiotherapy interventions for specific
      clinical conditions associated with shoulder pain, for shoulder pain where
      combinations of physiotherapy interventions, as well as, physiotherapy
      interventions as an adjunct to other, non physiotherapy interventions are
      compared. This is more reflective of current clinical practice. Trials should be
      adequately powered and address key methodological criteria such as allocation
      concealment and blinding of outcome assessor.

PMID- 12804510
TI  - Intensity of exercise for the treatment of osteoarthritis.
AB  - BACKGROUND: Therapeutic exercise is used as one modality to treat people with
      osteoarthritis (OA). OBJECTIVES: To evaluate the effectiveness of therapeutic
      exercise of differing intensities on objective and subjective measures of disease
      activity in people with OA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Pedro,
      Current Contents, Sports Discus and CINAHL up to and including December 2002. The
      Cochrane Field of Rehabilitation and Related Therapies and the Cochrane
      Musculoskeletal Review Group were also contacted for a search of their
      specialized registers. Handsearching was conducted on all retrieved articles for
      additional studies. SELECTION CRITERIA: Comparative controlled studies, such as
      randomized controlled trials, controlled clinical trials, cohort studies or
      case/control studies, of therapeutic exercises compared to control or active
      interventions in people with OA were eligible. No language restrictions were
      applied. Abstracts were also accepted. DATA COLLECTION AND ANALYSIS: Two
      independent reviewers identified potential articles from the literature search.
      These reviewers extracted data using pre-defined extraction forms. Consensus was
      reached on all data extraction. The two reviewers used a five point scale to
      assess the quality of the selected articles. Randomization, double-blinding and
      description of withdrawals were assessed. MAIN RESULTS: One study involving 39
      participants met the inclusion criteria. The review indicates that there were no
      significant differences between high intensity and low intensity aerobic exercise
      on participants with OA of the knee for functional status, gait, pain and aerobic
      capacity (Mangione 1999). REVIEWER'S CONCLUSIONS: Both high intensity and low
      intensity aerobic exercise appear to be equally effective in improving a
      patient's functional status, gait, pain and aerobic capacity for people with OA
      of the knee. Further research involving a greater number of subjects, and a
      larger number of studies involving a control group is needed to further
      substantiate these results.

PMID- 12804511
TI  - Continuous passive motion following total knee arthroplasty.
AB  - BACKGROUND: Knee arthroplasty (KA) is a common intervention that can enhance the
      quality of life for patients with osteoarthritis (OA) and rheumatoid arthritis
      (RA). Post-surgery rehabilitation protocols often include continuous passive
      motion (CPM). However, CPM protocols vary considerably amongst institutions.
      OBJECTIVES: The purpose of the current meta-analysis is to evaluate the
      effectiveness of continuous passive motion following total knee arthroplasty.
      SEARCH STRATEGY: An electronic search of MEDLINE (1966 to 2002), EMBASE (1988 to
      2002), CINAHL (1982 to 2002), HEALTH STAR (1991 to 1994) and CURRENT CONTENTS
      (1997 to 2002) was conducted to identify randomized controlled trials. SELECTION
      CRITERIA: Following an a priori protocol, only randomized controlled trials of
      CPM for the treatment of participants post KA were eligible. Subjects were 18
      years of age or older and had a pre-surgery diagnosis of degenerative joint
      disease. Both the experimental and control groups received physiotherapy. In
      addition to the physiotherapy intervention, the experimental group received CPM.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for
      inclusion. Data were then extracted and the quality of the trial assessed using
      predetermined forms. Outcome measures of interest were: active and passive knee
      range of motion (ROM) length of hospital stay, pain, swelling and quadriceps
      strength. A fixed effects model was used throughout for continuous variables,
      except where heterogeneity existed; in which case, a random effects model was
      used. Results were analyzed as weighted mean differences (WMD) with 95%
      confidence intervals (CI). Standardized mean differences (SMD) were used when
      different scales were used to measure the same concept (e.g. pain). Dichotomous
      outcomes were presented as a relative risk. MAIN RESULTS: Fourteen trials were
      retained for analysis. Results favouring CPM were found for the main comparison
      of CPM combined with physiotherapy (PT) versus PT alone at end of treatment. For
      the primary outcomes of interest, CPM combined with PT was found to statistically
      significantly increase active knee flexion (WMD 4.30 degrees, 95% CI: 1.96, 6.63)
      and decrease length of stay (WMD -0.69 days, 95% CI: -1.35, -0.03). CPM was also
      found to decrease the need for post-operative manipulation (RR 0.12, 95% CI:
      0.03, 0.53). CPM did not significantly improve passive knee flexion and passive
      or active knee extension. REVIEWER'S CONCLUSIONS: CPM combined with PT, may offer
      beneficial results compared to PT alone in the short term rehabilitation
      following total knee arthroplasty.

PMID- 12804512
TI  - Physical methods for treating fever in children.
AB  - BACKGROUND: Health workers recommend bathing, sponging and other physical methods
      to treat fever in children and to avoid febrile convulsions. We know little about
      the most effective methods, or how these methods compare with commonly used
      drugs. OBJECTIVES: To evaluate the benefits and harms of physical cooling methods
      used for managing fever in children. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group specialized trials register (February 2003), the
      Cochrane Central Register of Controlled Trials (Issue 1, 2003), MEDLINE (1966 to
      February 2003), EMBASE (1988 to November 2002), CINHAL (1982 to February 2003),
      LILACS (February 2003), Science Citation Index (1981 to February 2003), and
      reference lists of articles. We also contacted researchers in the field.
      SELECTION CRITERIA: Randomized and quasi-randomized trials comparing physical
      methods with a drug placebo or no treatment in children with fever of presumed
      infectious origin. Studies where children in both groups were given an
      antipyretic drug were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial methodological quality. One reviewer extracted data
      and the other checked the data for accuracy. Results were expressed as Relative
      Risk (RR) with 95% confidence intervals (CI) for discrete variables, and weighted
      mean differences for continuous outcomes. MAIN RESULTS: Seven trials, involving
      467 participants, met the inclusion criteria. One small trial (n = 30), comparing
      physical methods with drug placebo, did not demonstrate a difference in the
      proportion of children without fever by one hour after treatment in a comparison
      between physical methods alone and drug placebo. In 2 studies, where all children
      received an anti-pyretic drug, physical methods resulted in a higher proportion
      of children without fever at one hour (n=125, RR 11.8, CI 3.39 to 40.8). I; in a
      third study (n=130), which only reported mean change in temperature, no
      differences wereas detected. Mild adverse events (shivering and goose pimples)
      were more common in the physical methods group (3 trials, RR 5.09; CI 1.56 to
      16.60). REVIEWER'S CONCLUSIONS: A few small studies demonstrate that tepid
      sponging helps to reduce fever in children.

PMID- 12804513
TI  - Indicators of benzene emissions and exposure in Bangkok street.
AB  - Ambient benzene measurements were conducted for the first time at four air
      monitoring sites in the Bangkok metropolitan region (BMR), from January to
      December 2001. Analytical results show that the mean benzene concentrations range
      from 42.4 micro g/m(3) at the Din Daeng urban site to 15.1 micro g/m(3) at the
      Chaeng Wattana suburban site. The monitoring results show that at a larger
      distance from the roadside or a higher level from the street surface, the level
      of benzene decreases. Analysis of the ambient benzene concentrations was carried
      out with reference to meteorological influences and traffic density. In traffic
      analysis, the combined effects of street topography and traffic flows established
      high impact on the overall benzene concentration in Bangkok. Statistical analysis
      shows good correlations of blood benzene levels and trans, trans-muconic acid
      with ambient benzene and demonstrated substantial exposure from traffic.

PMID- 12804514
TI  - The effect of lead-based paint hazard remediation on blood lead levels of lead
      poisoned children in New York City.
AB  - Despite the widespread use of lead paint hazard control for children with lead
      poisoning, few controlled studies that estimate the effect of such control on
      children's blood lead levels have been published. This retrospective follow-up
      study examined the effects of lead hazard remediation and its timing on the blood
      lead levels of lead-poisoned children. From the New York City child blood lead
      registry, 221 children were selected who had an initial blood lead level of 20-44
      micro g/dL between 1 July 1994 and 31 December 1996; were 6 months to 6 years of
      age; had a report of a follow-up blood lead test between 10 and 14 months after
      the initial test; had a lead-based paint hazard identified in the primary
      dwelling unit prior to the 10- to 14-month follow-up blood lead test; had resided
      or spent time at only one address with an identified lead-based paint hazard; and
      were not chelated. The decline in geometric mean blood lead levels from baseline
      to 10-14 months later was compared for children whose homes were remediated and
      whose homes were not remediated during the follow-up period. Regardless of
      remediation, geometric mean blood lead levels declined significantly from 24.3
      micro g/dL at the initial diagnosis to 12.3 micro g/dL at the 10- to 14-month
      follow-up blood lead test (P<0.01). Among the 146 children whose homes were
      remediated the geometric mean blood lead levels declined 53% compared to 41%
      among the 75 children whose homes were not remediated by the follow-up blood lead
      test, a remediation effect of approximately 20% (P<0.01). After adjusting for
      potential confounders, the remediation effect was 11%, although it was no longer
      significant. Race was the only factor that appeared to confound the relationship:
      Black children had higher follow-up blood lead levels even after controlling for
      other factors, including the natural logarithm of the initial blood lead level.
      The effect of remediation appeared to be stronger for younger (10 to <36 months
      old) than for older (36 to 72 months old) children (P=0.06). While children in
      homes with earlier remediation (within less than 3 months) appeared to have
      greater declines in blood lead levels at the follow-up test than children in
      homes with later remediation (after 3 or more months), this trend was not
      significant when controlling for confounding factors. The findings of this study
      suggest that early identification of lead-poisoned children and timely
      investigation and abatement of hazards contribute to reducing blood lead levels.
      However, the apparent effect is modest and further research is needed to
      systematically test and improve the effectiveness of lead hazard controls.

PMID- 12804515
TI  - Urban air pollution induces micronuclei in peripheral erythrocytes of mice in
      vivo.
AB  - In this study, we explored the role of chronic exposure to urban air pollution in
      causing DNA damage (micronuclei frequency in peripheral erythrocytes) in rodents
      in vivo. Mice (n=20) were exposed to the urban atmosphere of Sao Paulo for 120
      days (February to June 1999) and compared to animals (n=20) maintained in the
      countryside (Atibaia) for the same period. Daily levels of inhalable particles
      (PM10), CO, NO(2), and SO(2), were available for Sao Paulo. Occasional
      measurements of CO and O(3) were made in Atibaia, showing negligible levels of
      pollution in the area. The frequency of micronuclei (repeated-measures ANOVA)
      increased with aging, the highest values obtained for the 90th day of experiment
      (P<0.001). The exposure to urban air pollution elicited a significant (P=0.016)
      increase of micronuclei frequency, with no significant interaction with time of
      study. Associations (Spearman's correlation) between pollution levels of the week
      that precede blood sampling and micronuclei counts were observed in Sao Paulo.
      The associations between micronuclei counts and air pollution were particularly
      strong for pollutants associated with automotive emissions, such as CO (P=0.037),
      NO(2) (P<0.001), and PM10 (P<0.001). Our results support the concept that urban
      levels of air pollution may cause somatic mutations.

PMID- 12804516
TI  - Lead exposure potentiates predatory attack behavior in the cat.
AB  - Epidemiologic studies have demonstrated that environmental lead exposure is
      associated with aggressive behavior in children; however, numerous confounding
      variables limit the ability of these studies to establish a causal relationship.
      The study of aggressive behavior using a validated animal model was used to test
      the hypothesis that there is a causal relationship between lead exposure and
      aggression in the absence of confounding variables. We studied the effects of
      lead exposure on a feline model of aggression: predatory (quiet biting) attack of
      an anesthetized rat. Five cats were stimulated with a precisely controlled
      electrical current via electrodes inserted into the lateral hypothalamus. The
      response measure was the predatory attack threshold current (i.e., the current
      required to elicit an attack response on 50% of the trials). Blocks of trials
      were administered in which predatory attack threshold currents were measured
      three times a week for a total of 6-10 weeks, including before, during, and after
      lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150
      mg/kg/day. Two of the five cats received a second period of lead exposure. Blood
      lead concentrations were measured twice a week and were <1, 21-77, and <20 micro
      g/dL prior to, during, and after lead exposure, respectively. The predatory
      attack threshold decreased significantly during initial lead exposure in three of
      five cats and increased after the cessation of lead exposure in four of the five
      cats (P<0.01). The predatory attack thresholds and blood lead concentrations for
      each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed
      model demonstrated a significant (P=0.0019) negative association between
      threshold current and blood lead concentration. The data of this study
      demonstrate that lead exposure enhances predatory aggression in the cat and
      provide experimental support for a causal relationship between lead exposure and
      aggressive behavior in humans.

PMID- 12804517
TI  - In vitro modulation of prolactin mRNA by toxaphene and 3,3',4,4'
      tetrachlorobiphenyl.
AB  - It is now well recognized that many environmental contaminants are capable of
      disrupting endocrine processes in a variety of species, including birds, mammals,
      reptiles, and fish. Among these contaminants are toxaphene and polychlorinated
      biphenyls (PCBs), two of the most prevalent contaminants present in aquatic food
      chains of the Great Lakes and the Canadian Arctic region. We set out to
      investigate the possible endocrine-modulating activities of toxaphene, the PCB
      congener 3,3',4,4'-tetrachlorobiphenyl (TeCB), an equimolar mixture of both
      compounds (toxaphene/TeCB), and estradiol (E(2)) (E(2)/toxaphene, E(2)/TeCB) on
      prolactin (PRL) mRNA expression. Concentrations ranging from 10(-7) to 10(-11)M
      for both toxaphene and TeCB were assayed but only toxaphene modulated PRL mRNA
      levels, as determined by relative quantitative reverse transcriptase-polymerase
      chain reaction. Maximal induction by toxaphene was seen at 10(-7)M, resulting in
      a fourfold increase in PRL mRNA levels. No interactions were observed for
      combinations of the test substances. Our study demonstrates that toxaphene may
      exhibit estrogen-like activity by modulating PRL mRNA levels in GH(3) cells.

PMID- 12804518
TI  - Brief exposure to triphenyltin produces irreversible inhibition of the cytotoxic
      function of human natural killer cells.
AB  - Phenyltin (PT) compounds (mono-, di-, and triphenyltins) are used in agricultural
      and consumer products. They contaminate the environment and have toxic effects on
      aquatic and terrestrial animals including humans. In an earlier study we
      demonstrated that PTs (1 micro M, for 1h in vitro exposure) could cause
      considerable inhibition of the tumor-killing function of human natural killer
      (NK) cells (as much as 85%). In this study we examined whether cytotoxic function
      can be recovered after a brief exposure (1h) to PTs. Freshly isolated lymphocytes
      were exposed to triphenyltin (TPT) or diphenyltin (DPT) for 1h. The compound was
      then removed and the cells were incubated in PT-free medium for as long as 6
      days. The results indicated that exposure to 750nM TPT for 1h caused an
      approximately 63+/-10% decrease in NK-cytotoxic function. However, if the cells
      were exposed to 750nM TPT for 1h and then allowed to incubate in TPT-free medium
      for 24h, there was a 91+/-12% loss of cytotoxic function. NK-cytotoxic function
      remained inhibited for as long as 6 days after removal of the TPT. A 1-h exposure
      to as much as 5 micro M DPT caused no loss of NK-cytotoxic function when the
      cells were tested immediately after the exposure. However, if the cells were
      allowed to incubate in DPT-free medium for 24h after the 1-h exposure to 5 micro
      M DPT, cytotoxicity was inhibited by 68+/-29% and this inhibition persisted for
      at least 6 days. These results indicated that short-term exposure to PTs caused
      persistent negative effects on human NK-cell function. The persistent effects of
      PTs are compared to those of the butyltins (BTs).

PMID- 12804519
TI  - Hierarchical sampling of multiple strata: an innovative technique in exposure
      characterization.
AB  - Sampling of multiple strata, or hierarchical sampling of various exposure sources
      and activity areas, has been tested and is suggested as a method to sample (or to
      locate) areas with a high prevalence of elevated blood lead in children.
      Hierarchical sampling was devised to supplement traditional soil lead sampling of
      a single stratum, either residential or fixed point source, using a multistep
      strategy. Blood lead (n=1141) and soil lead (n=378) data collected under the
      USEPA/UCI Tijuana Lead Project (1996-1999) were analyzed to evaluate the
      usefulness of sampling soil lead from background sites, schools and parks, point
      sources, and residences. Results revealed that industrial emissions have been a
      contributing factor to soil lead contamination in Tijuana. At the regional level,
      point source soil lead was associated with mean blood lead levels and concurrent
      high background, and point source soil lead levels were predictive of a high
      percentage of subjects with blood lead equal to or greater than 10 micro g/dL (pe
      10). Significant relationships were observed between mean blood lead level and
      fixed point source soil lead (r=0.93; P<0.05; R(2)=0.72 using a quadratic model)
      and between residential soil lead and fixed point source soil lead (r=0.90;
      P<0.05; R(2)=0.86 using a cubic model). This study suggests that point sources
      alone are not sufficient for predicting the relative risk of exposure to lead in
      the urban environment. These findings will be useful in defining regions for
      targeted or universal soil lead sampling by site type. Point sources have been
      observed to be predictive of mean blood lead at the regional level; however, this
      relationship alone was not sufficient to predict pe 10. It is concluded that when
      apparently undisturbed sites reveal high soil lead levels in addition to local
      point sources, dispersion of lead is widespread and will be associated with a
      high prevalence of elevated blood lead in children. Multiple strata sampling was
      shown to be useful in differentiating among sources by site-specific association
      to mean blood lead and the prevalence of elevated blood lead at the regional
      level.

PMID- 12804520
TI  - Fish are central in the diet of Amazonian riparians: should we worry about their
      mercury concentrations?
AB  - The Amazon rain forest extends over an area of 7.8x10(6)km(2) in nine countries.
      It harbors a diverse human population distributed in dense cities and isolated
      communities with extreme levels of infrastructure. Amazonian forest people,
      either autochthons or frontier riparians (ribeirinhos) living in isolated areas,
      share the same environment for survival and nutritional status. The peculiarities
      of the hydrological cycle determine disease patterns, agricultural conditions,
      and food availability. Feeding strategies depend heavily on cassava products and
      fish. These two foods carry toxic substances such as linamarin (naturally present
      in cassava) and monomethyl mercury (MMHg) (bioconcentrated in fish flesh) that
      cause neurotoxic diseases in other parts of the world but not in Amazonia, where
      neurotoxic cases of food origin are rare and not related to these staples. While
      cassava detoxification processes may partly explain its safe consumption, the Hg
      concentrations in Amazonian fish are within traditionally safe limits for this
      population and contribute to an important metabolic interaction with cassava. The
      gold rush of the 1970s and 1980s brought large-scale environmental disruption and
      physical destruction of ecosystems at impact points, along with a heavy discharge
      of metallic Hg. The discharged Hg has not yet impacted on MMHg concentrations in
      fish or in hair of fish consumers. Hair Hg concentration, used as a biomarker of
      fish consumption, indicates that the Amazonian riparians are acquiring an
      excellent source of protein carrying important nutrients, the lack of which could
      aggravate their existing health problems. Therefore, in a scenario of
      insufficient health services and an unhealthy environment, food habits based on
      fish consumption are part of a successful survival strategy and recommendations
      for changes are not yet justifiable.

PMID- 12804521
TI  - Indoor aldehydes: measurement of contamination levels and identification of their
      determinants in Paris dwellings.
AB  - The recent increased prevalence of childhood asthma and atopy has brought into
      question the impact of outdoor pollutants and indoor air quality. The
      contributory role of aldehydes to this problem and the fact that they are mainly
      derived from the domestic environment make them of particular interest. This
      study therefore measures six different aldehyde levels in Paris dwellings from
      potentially different sources and identifies their indoor determinants. The study
      was carried out in the three principal rooms of 61 flats with no previous history
      of complaint for olfactory nuisance or specific symptoms, two-thirds of the flats
      having been recently refurbished. Aldehydes were sampled in these rooms using
      passive samplers, and a questionnaire on potential aldehyde sources was filled
      out at the same time. A multiple linear regression model was used to investigate
      indoor aldehyde determinants. Our study revealed that propionaldehyde and
      benzaldehyde were of minor importance compared to formaldehyde, acetaldehyde,
      pentanal, and hexanal. We found that levels of these last four compounds depended
      on the age of wall or floor coverings (renovations less than 1 year old),
      smoking, and ambient parameters (carbon dioxide levels, temperature). These
      results could help in the assessment of indoor aldehyde emissions.

PMID- 12804522
TI  - Fish, shellfish, and meat meals of the public in Singapore.
AB  - Understanding different patterns of fish consumption is an important component of
      the assessment of risk from contaminants in fish. While there have been extensive
      studies of fish consumption in Western cultures, less attention has been devoted
      to the role of fish and meat in the diets of people in other cultures. A survey
      of 212 people living in Singapore was conducted to examine the relative
      importance of fish, shellfish, and other meat in their diets and to ascertain
      whether there were differences as a function of age, income, education or gender.
      As expected, fish and shellfish played an important role in their daily diets. On
      average, people ate fish in about 10 meals a week, chicken for eight meals, and
      shrimp and pork for about six meals each. While nearly 8% never ate fish, 18% ate
      fish at all 21 meals a week and over 20% ate shellfish for all 21 meals. Income
      explained about 14% of the variation in the number of fish meals consumed, and
      age explained about 8% of the variation in number of chicken meals per week.
      There were no gender differences in the number of meals of each type. People less
      than 26 years old ate significantly more pork, chicken, and other meat meals and
      fewer shellfish meals than older people. People with higher incomes ate
      significantly more fish meals than those with lower incomes. Chinese individuals
      ate significantly more meals of pork, chicken, and other meat than other ethnic
      groups, and they ate only 26% of their meals at home, while others ate 33% of
      their meals at home. The data indicate a great deal of variation in the number of
      meals of fish, shellfish, and other meats eaten by the people interviewed, making
      dietary and risk assessments challenging.

PMID- 12804523
TI  - The bioaccumulation of nonyphenol and its adverse effect on the liver of rainbow
      trout (Onchorynchus mykiss).
AB  - Alkylphenol polyethoxylates (APEs) are widely used as nonionic surfactants.
      Nonylphenol (NP), one of the derivatives of APEs, has been found in the aquatic
      environment in ranges from nanograms per liter to milligrams per liter. In this
      study, juvenile rainbow trout were exposed to 0 (control), 66, 220, or 660 micro
      g NP/L for up to 28 days. Fish remained healthy under NP exposures of 0, 66, and
      220 micro g/L for the length of the experiment. All fish died after 4 days of
      exposure to 660 micro g NP/L. Time-dependent NP bioaccumulation was detected in
      the tissues of fish exposed to 220 micro g NP/L (P<0.05) and histopathological
      changes were observed in the livers of fish exposed to 220 micro g NP/L.
      Furthermore, an increase in the activity of glutathione-S-transferase (GST) was
      found in the liver of fish exposed to 220 micro g NP/L for 1 week (P<0.05). There
      was an increase in GST activity in the liver of fish exposed to 66 micro g NP/L
      but it did not occur before 2 weeks of exposure to NP. The GST activity then
      decreased in a time-dependent manner in treatment groups, and this decrease was
      lower in the livers of fish treated with 66 and 220 micro g NP/L than in control
      fish after 3 weeks of exposure (P<0.05). These results indicated that sublethal
      doses of NP were accumulating in the bodies of the fish and causing
      histopathological and biochemical changes in the livers of rainbow trout.

PMID- 12804524
TI  - Comparative toxicity of tetra ethyl lead and lead oxide to earthworms, Eisenia
      fetida (Savigny).
AB  - Leaded gasoline contains tetra ethyl lead (TEL) as an antiknocking agent, which
      produces major amounts of lead oxide in automobile exhaust along with traces of
      TEL. To minimize the lead contamination, methyl tertiary butyl ether (MTBE) is
      used as a substitute for producing unleaded gasoline. It has become increasingly
      apparent that young children are highly susceptible to the harmful effects of
      lead. Hence, a study was carried out to monitor lead toxicity in soil, using
      adult earthworms (Eisenia fetida, Savigny). Leaded gasoline (TEL) and lead oxide
      are 383- and 211-fold more toxic than unleaded gasoline (MTBE) in 7 days of
      exposure and 627- and 290-fold more toxic in 14 days, respectively. Results
      indicate that the presence of TEL in leaded gasoline and lead oxide has a
      significant effect on behavior, morphology, and histopathology of earthworms.
      Absorption of TEL into the tissues is comparatively less than that of lead oxide
      but toxic effects were severe. Rupture of the cuticle, extrusion of coelomic
      fluid and inflexible metameric segmentation were observed, causing
      desensitization of the posterior region leading to fragmentation in earthworms.

PMID- 12804525
TI  - Levels of heavy metals (Fe, Cu, Ni, Cr, Pb, and Zn) in tissue of Mugil cephalus
      and Trachurus mediterraneus from Iskenderun Bay, Turkey.
AB  - Concentrations of iron, copper, nickel, chromium, lead, and zinc were determined
      in the muscle, skin and gonads of Mugil cephalus and Trachurus mediterraneus
      caught at three stations in Iskenderun Bay, Turkey. Heavy metal concentrations in
      the tissues tended to vary significantly among stations, and two stations thought
      to be contaminated by untreated domestic wastes and surrounding industrial
      environment showed particularly high metal concentrations. Generally, skin and
      gonads showed higher metal concentrations than muscle. The ranges of mean
      concentrations (micro g/g wet wt) in M. cephalus were as follows: the range of
      iron concentration was 70.28, 149.77, and 382.51, that of copper was 1.45, 5.36,
      and 35.37, that of nickel was 1.22, 2.72, and 7.35, that of chromium was 1.46,
      3.22, and 10.06, that of lead was 7.45, 37.39, and 62.33, and that of zinc was
      38.23, 100.56, and 281.51 in the muscle, skin, and gonads, respectively. The
      ranges of mean concentrations (micro g/g wet wt) in T. mediterraneus were as
      follows: the range of iron concentration was 41.84, 49.86, and 74.20, that of
      copper was 1.29, 3.33, and 11.37, that of nickel was 0.94, 2.02, and 0.99, that
      of chromium was 1.28, 10.90, and 10.60, that of lead was 1.03, 4.78, and 8.41,
      and that of zinc was 19.55, 60.79, and 38.44 in the muscle, skin, and gonads,
      respectively. The concentrations of some metals in some tissues exceeded the
      acceptable levels for a food source for human consumption. The results of this
      study indicated that the metals present in the bay were taken up by two fish
      species through food, water, and sediment, and regardless of their biological
      needs showed high metal concentrations.

PMID- 12804526
TI  - Mathematical modeling of thymopoiesis in HIV infection: real data, virtual data,
      and data interpretation.

PMID- 12804527
TI  - The complement system as a therapeutic target in autoimmunity.

PMID- 12804528
TI  - Induction of apoptosis in human blood T cells by 7,8-dihydroneopterin: the
      difference between healthy controls and patients with systemic lupus
      erythematosus.
AB  - Neopterin (Neo) and 7,8-dihydroneopterin (H(2)Neo) are produced by human monocyte
      derived macrophages upon stimulation with IFN-gamma. Increased amounts of Neo and
      H(2)Neo in human body fluids are found in many disorders, including viral
      infections and autoimmune diseases. Recent data suggest that neopterin
      derivatives may exhibit distinct biochemical functions activating redox-sensitive
      transcription factors and inducing apoptosis in various cell lines. In this study
      we investigated the effect of H(2)Neo on human peripheral blood T cells (PBT)
      from healthy blood donors in comparison with PBT isolated from patients with
      systemic lupus erythematosus (SLE). H(2)Neo induced apoptosis in healthy PBT in a
      concentration-dependent manner. In short time culture, a significantly lower
      ability of PBT isolated from patients with SLE to undergo apoptosis in response
      to H(2)Neo compared to healthy controls was detected. Our results suggest a
      possible role of the neopterin derivative H(2)Neo in T cell apoptosis mediated by
      stimulated monocytes/macrophages.

PMID- 12804529
TI  - Identification of oligoclonal CD4 T cells in diffuse large B cell lymphomas.
AB  - Human B cell lymphomas often contain CD4 T cells. Here we show that, in diffuse
      large B cell lymphomas (DLCL), such T cells are oligoclonal. The CDR3 lengths and
      nucleotide sequences of oligoclonal TCRBV of CD4 T cells in an original and
      relapsed lymphoma from one patient were compared. Three BV23 sequences were
      identical (12/17 and 16/16 clones in primary and relapsed lymphomas,
      respectively), but were absent in CD4 T cells from another patient's DLCL. Two of
      the repetitive BV23 sequences were found in peripheral blood CD4 T cells (5/17
      clones); gamma-irradiated DLCL from this patient stimulated syngeneic BV23
      response in CD4 cells (92% of BV23 had the same CDR3 length). Skew in TCRBV
      representation was observed in CD4 T cells from all the DLCL. One DLCL, with
      overrepresentation of BV13S1 in CD4 cells, stimulated the same TCR in CD4 cells
      from three unrelated individuals. These findings support the conclusion that
      there is clonal selection of CD4 T cells in DLCL.

PMID- 12804530
TI  - Type I IFNs differentially modulate IL-12p70 production by human dendritic cells
      depending on the maturation status of the cells and counteract IFN-gamma-mediated
      signaling.
AB  - Type I IFNs (IFNalpha/beta) are approved for the treatment of a variety of
      diseases, including the autoimmune disease multiple sclerosis (MS). The
      proinflammatory cytokines IL-12 and IFN-gamma have been proposed to contribute to
      the pathogenesis of MS. Since dendritic cells (DCs) are recognized as major
      producers of IL-12p70 and promote the development of IFN-gamma-producing Th1
      cells, we investigated the direct effect of IFNalpha/beta on monocyte-derived DCs
      at different stages of development. We demonstrate that IFNalpha/beta enhance IL
      12p70 production by immature DCs but inhibit IL-12p70 production by mature DCs.
      Importantly, IFNalpha/beta strongly counteracted the IL-12-enhancing effect of
      IFN-gamma on DCs irrespective of their maturation status. Exposure of DCs to
      IFNalpha/beta during maturation does not affect their maturation or cytokine
      profile upon CD40 ligation. The differential modulatory effect of IFNalpha/beta
      on the IL-12-producing capacity of DCs and their cross-regulatory effect on IFN
      gamma may reduce inflammatory processes and therefore be therapeutically
      effective in MS.

PMID- 12804531
TI  - Role of monocytes and eosinophils in human respiratory syncytial virus infection
      in vitro.
AB  - RSV infection in airway epithelial cells (EC) results in production of the
      chemokines RANTES and MIP1alpha and the leukocyte differentiation factor GM-CSF.
      The chemokines attract monocytes and eosinophils to the site of infection, where
      GM-CSF may influence their function and differentiation. In turn, these
      inflammatory cells may limit the progression of RSV infection, as well as
      initiate immune responses. In the present study, the effect of monocytes and
      eosinophils on viral replication and infection-dependent release of EC-derived
      cytokines was investigated. The modulation of immune cell costimulatory
      molecules, CD80, CD86, CD40, and HLA-DR, and the release of the CD4(+) T cell
      chemoattractant IL-16 were also investigated. Employing immunofluorescence
      techniques, monocytes and eosinophils in cocultures with infected EC were found
      to inhibit the spread of RSV to uninfected cells. Monocytes also had a
      significant effect on replication of RSV. Monocytes phagocytized the virus, while
      eosinophils inhibited reinfection mainly by extracellular means. The release of G
      CSF and GM-CSF in the infected cultures was not significantly affected by either
      monocytes or eosinophils, while RANTES release was significantly decreased. The
      expression of CD40, CD80, CD86, and HLA-DR on monocytes, but not on eosinophils,
      increased in an RSV-dose-dependent manner. IL-16 release was not induced in RSV
      infected EC, but was significantly increased in coculture with monocytes. These
      results suggest that both monocytes and eosinophils attracted to the site of RSV
      infection play an important role in confining infection, while RSV-exposed
      monocytes may be involved in promoting/polarizing immune responses to RSV.

PMID- 12804532
TI  - Effect of genetic deficiency of terminal deoxynucleotidyl transferase on
      autoantibody production and renal disease in MRL/lpr mice.
AB  - Terminal deoxynucleotidyl transferase (TdT) places non-template-coded nucleotides
      (N additions) in the VH CDR3 of T cell receptors and immunoglobulins. Amino acids
      coded for by N additions are important in autoantibody binding of dsDNA in lupus.
      We hypothesized that a genetic lack of TdT would modulate disease in lupus-prone
      mice. To test this hypothesis, we derived TdT-deficient MRL/lpr mice. Serum
      levels of anti-dsDNA antibodies and anti-dsDNA producing splenocytes were
      significantly lower in the TdT(-) versus TdT(+) littermates. Albuminuria,
      glomerular IgG deposition, and pathologic renal disease were significantly
      reduced in the TdT(-) mice. Sequence analysis of anti-dsDNA hybridomas derived
      from TdT(-) mice revealed a lack of N additions, short VH CDR3 segments, yet the
      presence of VH CDR3 arginines. Thus, the genetic absence of TdT reduces
      autoantibody production and clinical disease in MRL/lpr mice, confirming the
      importance of N additions in the autoimmune response in these mice.

PMID- 12804533
TI  - Potential limitations in using minor histocompatibility antigen-specific
      cytotoxic T cells for targeting solid tumor cells.
AB  - We have shown previously that KIAA0223, a gene encoding a minor
      histocompatibility antigen, HA-1, whose expression was believed to be restricted
      to the hematopoietic cells, is aberrantly expressed in some solid tumor cell
      lines. However, its significance in tumor immunity needs to be determined.
      Cytotoxic activity of HA-1(H)-specific cytotoxic T lymphocytes (CTLs) was
      assessed against solid tumor cell lines expressing KIAA0223 using (51)Cr release
      assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately
      expressed. One of the two CTL-resistant cell lines became susceptible after
      treatment with IFN-gamma and TNF-alpha, while the other was lysed only after
      pulsing with HA-1(H) peptide. In most cell lines tested, HA-1(H) peptide was
      properly generated and presented for recognition by the CTL. However, impaired
      antigen processing and presentation observed in this study may result in escape
      from CTL recognition in vivo, as well as in vitro, as observed in this study.

PMID- 12804534
TI  - Comment on Plebani et al.'s report.

PMID- 12804536
TI  - Double mandibular osteotomy with coronoidectomy for tumours in the parapharyngeal
      space.
AB  - Removal of deep-lobe parotid tumours from the parapharyngeal space is often
      difficult because of limited surgical access and the critical vascular and
      neurologic structures nearby. Mandibulotomy, when necessary, is useful for
      improving wider visibility and control of the vascular bundle and facial nerve,
      but may cause damage to the inferior dental and lingual nerves. The double
      mandibular osteotomy with coronoidectomy gives excellent access and avoids damage
      to these nerves.

PMID- 12804537
TI  - Predictive variables for the biological behaviour of basal cell carcinoma of the
      face: relevance of morphometry of the nuclei.
AB  - We did a morphometric analysis of 130 histological sections of basal cell
      carcinoma (BCC) of the face to find out whether morphometric variables in the
      structure of the nuclei of BCC cells could serve as predictors of the biological
      behaviour. We considered the following variables: maximum and minimum diameters,
      perimeter, nuclear area and five form factors that characterise and quantify the
      shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear
      roundness and circumference ratio). We did a statistical analysis of primary and
      recurring tumours and four histology-based groups (multifocal superficial BCCs,
      nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test
      for independent samples. Multifocal superficial BCCs showed significantly smaller
      values for the directly measured variables (maximum and minimum diameters,
      perimeter and nuclear area). Morphometry could not distinguish between primary
      and recurring tumours.

PMID- 12804538
TI  - A "round block" purse-string suture in facial reconstruction after operations for
      skin cancer surgery.
AB  - Removal of skin cancers in the head and neck region usually results in a circular
      or oval defect, which must be reconstructed immediately using one of several
      techniques. Larger defects can present a difficult aesthetic problem. The purse
      string suture is particularly suited to such large defects where the skin is lax.
      We report 51 cases where this technique was used in the head and neck region. All
      defects were considerably reduced in size and some required a small skin graft to
      complete the reconstruction. Initially many redundant skin folds and considerable
      local distortion were seen but these improved with time. The technique is simple,
      inexpensive, and the results are satisfactory in appropriately selected cases.
      Comprehensive discussion to prepare patients for the gross initial distortion and
      the long period of retention of the suture makes the procedure acceptable to
      patients.

PMID- 12804539
TI  - Palmar arch backflow following radial forearm free flap harvest.
AB  - BACKGROUND: Most surgeons advocate an Allen test (for occlusion of the radial or
      ulnar artery) and Doppler ultrasound examination before harvesting a forearm
      flap. In this study we attempted to correlate the results of these tests with
      intraoperative measurement of backflow pressure in the radial artery stump.
      METHOD: Stump pressures were measured in 30 patients after the flap had been
      harvested and were compared with preoperative assessment and intraoperative
      measurements of mean arterial pressure (MAP). RESULTS: Mean arterial backflow
      pressure (MABP) in the arterial stump varied from 27 to 55mm Hg (mean 40.5). The
      ratio of this value to the mean arterial pressure ranged from 0.39 to 0.89 (mean
      0.59) and exceeding 0.5 in 21 patients (70%). There was no correlation between
      this ratio and the preoperative assessment. CONCLUSIONS: These findings suggest
      that in the presence of a satisfactory Allen test and Doppler examination, there
      is adequate pressure in the palmar system to maintain vascular integrity of the
      donor hand after sacrifice of the radial artery. Despite the possibility of
      anatomical variants, the routine use of more invasive imaging is unnecessary.

PMID- 12804540
TI  - Swallowing and speech function after intraoral soft tissue reconstruction with
      lateral upper arm free flap and radial forearm free flap.
AB  - Swallowing, speech, and morbidity were assessed postoperatively in 25 patients,
      18 of whom had had intraoral defects reconstructed by lateral upper arm free
      flaps (LUFF) and 7 by radial forearm free flaps (RFFF). Video fluoroscopy was
      used to assess swallowing, the Freiburger audiometric test to assess speech; and
      measurement of arm circumference to assess donor site morbidity. A questionnaire
      was used to evaluate swallowing, speech, and donor site morbidity subjectively.
      The degree of impairment in swallowing depended on the site of resection.
      Anterior and posterior resections affected swallowing more than lateral
      resections. Anterior resection and the use of LUFFs reduced intelligibility.
      There was no significant difference in impairment between LUFF and RFFF. We
      conclude that the LUFFs are superior to RFFFs because they can be closed primary
      and the incidence of donor site morbidity is slight.

PMID- 12804541
TI  - The moon and its relationship to oral and maxillofacial emergencies.
AB  - OBJECTIVE: To study the relationship between the full moon and oral and
      maxillofacial emergencies. STUDY DESIGN: Retrospective analysis of 2416 referrals
      to the Department of Oral and Maxillofacial Surgery, St. Bartholomews and The
      Royal London Hospital, London, over a 16-month period (17 lunar months).
      Frequency distributions were used to assess emergency workload during the week of
      the full moon. RESULTS: There was a rise in referrals in the latter part of the 7
      day period surrounding the full moon. There was a persistent reduction in
      emergency workload in the 3-day period leading up to the full moon. The results
      approach but do not reach significance. CONCLUSIONS: The effect of the moon on
      oral and maxillofacial referrals cannot be proven.

PMID- 12804542
TI  - Platelet-derived growth factor and bone morphogenetic protein in the healing of
      mandibular fractures in rats.
AB  - We studied the effects of platelet-derived growth factor-B (PDGF-B) and bone
      morphogenetic protein-2 (BMP-2) during the healing of mandibular closed fractures
      in rats by immunohistochemical methods. Unilateral closed fractures were created
      in the mandibles of thirty 12-week-old rats. BMP-2 was expressed during all
      stages of healing, but PDGF-B was expressed mainly in the early and middle
      stages, and not in the later stage of the healing process. We conclude that PDGF
      B was associated with the proliferation and migration of primitive mesenchymal
      cells. BMP-2 was related to the differentiation of mesenchymal cells into
      osteoblasts and chondroblasts. PDGF-B and BMP-2 both have distinct regulatory
      effects on the healing of fractures.

PMID- 12804543
TI  - Preliminary assessment of skeletal stability after sagittal split mandibular
      advancement using a bioresorbable fixation system.
AB  - We studied skeletal stability during the first year after mandibular advancement
      and fixation with bioresorbable self-reinforced poly-L-lactide (SR-PLLA) screws
      in 11 patients by cephalometric measurements. We compared these with a cohort of
      11 patients, in whom titanium screws were used for fixation. We found no
      significant difference between the two groups in the median preoperative
      cephalometric values and the median changes after operation. There was also no
      significant difference between the two groups regarding the median extent of
      relapse 1-year after operation. We conclude that bioresorbable SR-PLLA screws are
      comparable to metallic screws for fixation of bone after sagittal split
      mandibular advancement.

PMID- 12804544
TI  - Use of interdental distraction osteogenesis for orthodontic tooth alignment and
      correction of maxillary hypoplasia: a case report.

PMID- 12804545
TI  - Incidence of penetration of a blood vessel during inferior alveolar nerve block.
AB  - Aspiration of the syringe after the needle had been placed in position for an
      inferior alveolar nerve block (but before the anaesthetic solution was injected)
      in 250 patients showed that the tip of the needle was in a blood vessel in 49
      (20%). Aspiration of blood was significantly more common in patients aged 9-19
      years than in all others (P=0.04).

PMID- 12804547
TI  - Splinting the radial forearm free flap donor site.

PMID- 12804546
TI  - Surgical emphysema and Collet-Sicard syndrome after cryoblockade of the inferior
      alveolar nerve.
AB  - We present a case of Collet-Sicard syndrome (palsy of cranial nerves IX-XII)
      together with cervicofacial emphysema after cryoblockade to the mandibular
      division of the trigeminal nerve.

PMID- 12804548
TI  - Metastatic pulmonary ameloblastoma. An unusual case.
AB  - We present a patient who had a large metastatic pulmonary ameloblastoma resected
      25 years after removal of an apparently benign primary ameloblastoma of the jaw.
      It highlights three areas: problems with the histopathological diagnosis of
      pulmonary metastases using fine needle aspiration; a noted radiological
      improvement after a 5-year course of oral cyclophosphamide, in keeping with
      occasional patients who have responded to chemotherapy; and the technical
      difficulties of resection of a large pulmonary metastasis, particularly when it
      is adherent to the mediastinum.

PMID- 12804549
TI  - Primary malignant melanoma arising in the dorsum of the tongue.
AB  - We present the case of a 53-year-old White man with primary malignant melanoma of
      the dorsum of the tongue that arose in an area of widespread diffuse
      pigmentation. He was treated by wide excision and insertion of iridium pins (65Gy
      over 5 days). Ten months later he developed metastases that were treated by
      palliative irradiation.

PMID- 12804550
TI  - 'Mice' in the joint.

PMID- 12804551
TI  - Lingual traumatic ulceration (Riga-Fede disease).

PMID- 12804552
TI  - Re: Prolonged paraesthesia following inferior alveolar nerve block using
      articaine.

PMID- 12804553
TI  - Re: A prospective randomised trial of the benefits of a sternocleidomastoid flap
      after superficial parotidectomy.

PMID- 12804554
TI  - Re: Prolonged paraesthesia following inferior alveolar nerve block using
      articaine.

PMID- 12804555
TI  - Re: The use of superficial parotidectomy in the treatment of chronic
      sialadenitis.

PMID- 12804556
TI  - Re: Aesthetic facial surgery.

PMID- 12804558
TI  - Re: Training in maxillofacial surgery.

PMID- 12804557
TI  - Re: Training in maxillofacial surgery.

PMID- 12804560
TI  - Re: High serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in mothers of
      children with cleft lip.

PMID- 12804561
TI  - Re: Rhinoplasty and OMFS.

PMID- 12804562
TI  - Re: Wales CJ, Matthews NS. Use of stoma bags to cover extraoral sites for
      incision and drainage. Br J Oral Maxillofac Surg 2002; 40: 339-340.

PMID- 12804565
TI  - Cell signaling in yeast sporulation.
AB  - Gametogenesis is essential for the propagation of all sexually reproducing
      organisms and consists of halving the chromosome number through meiosis, and the
      subsequent packaging of the haploid products into gametes. Meiosis and gamete
      formation must be tightly coupled to ensure the formation of viable progeny;
      perturbations result in infertility, inviability, and birth defects. In the yeast
      Saccharomyces cerevisiae, sexual reproduction occurs via sporulation and is
      similar in many respects to gametogenesis in mammals. An increasing number of
      conserved signaling molecules have been shown to be essential for yeast
      sporulation; recent studies reveal molecular insights into how these molecules
      regulate this intricate differentiation program.

PMID- 12804566
TI  - High levels of urinary midkine in various cancer patients.
AB  - Midkine (MK) is a heparin-binding growth factor, which promotes growth,
      migration, and survival of various cells, and MK expression is increased in many
      human carcinomas. We determined the urinary MK level by enzyme-linked
      immunoassay. Taking 311pg/mg creatinine as a cut-off level, 70% of patients with
      various carcinomas (n=142) gave positive values, while only 5.5% of healthy
      volunteers (n=330) did. In case of gastric carcinoma, 17 out of 21 patients with
      stage 1 tumor were positive. Urinary MK levels are expected to become a
      convenient marker as an aid in detection of tumors.

PMID- 12804567
TI  - Adipose differentiation-related protein has two independent domains for targeting
      to lipid droplets.
AB  - Adipose differentiation-related protein (ADRP) is a protein found in lipid
      droplets of many cell types. In contrast to several other proteins localized to
      lipid droplets, ADRP does not have a long hydrophobic domain. We investigated as
      to which portion of the molecule is important for localization to pre-existing
      lipid droplets. By truncating from the carboxyl-terminus, a segment of amino
      acids (aa) 1-181 of ADRP was found distributed to lipid droplets, but further
      deletion, e.g., aa 1-155, caused diffuse distribution in the cytoplasm. By amino
      terminal truncation, aa 167-426 was found mostly cytoplasmic, but surprisingly, a
      shorter mutant, e.g., aa 277-426, was distributed to lipid droplets. Still
      shorter mutants, e.g., aa 302-426, often distributed to mitochondria, and a
      mutant lacking aa 154-174 was found in the cytoplasm. Interestingly, expression
      of either aa 1-181 or aa 277-426, which are not overlapping each other, induced
      de novo formation of lipid droplets. The result indicates that ADRP has two
      independent domains related to its localization and lipid droplet biogenesis. The
      unique property found in the present study may be related to physiological
      function of ADRP.

PMID- 12804568
TI  - Identification of NDRG1 as an early inducible gene during in vitro maturation of
      cultured mast cells.
AB  - Coculture of mouse bone marrow-derived mast cells (BMMC) with fibroblasts in the
      presence of stem cell factor (SCF) facilitates morphological and functional
      maturation toward a connective tissue mast cell (CTMC)-like phenotype. By means
      of cDNA subtraction, we identified several inducible genes during this mast cell
      maturation process. Of approximately 100 sequenced clones induced, nearly 50%
      were chromosome 14-associated serine proteases. Approximately 14% encoded NDRG1,
      a 43-kDa cytosolic protein that has been implicated in cell differentiation.
      NDRG1 was distributed in the cytosol of cultured mast cells and CTMC in rat skin.
      Overexpression of NDRG1 in RBL-2H3 cells resulted in enhanced degranulation in
      response to various stimuli. Thus, NDRG1 may be a mast cell maturation-associated
      inducible protein that allows the cells to be susceptible to extracellular
      stimuli leading to degranulation. Additionally, several unique maturation
      associated inducible genes were identified, molecular and functional
      characterization of which will provide new insights into mast cell biology.

PMID- 12804569
TI  - Molecular cloning and characterization of a mouse spermatogenesis-related ring
      finger gene znf230.
AB  - Complete cDNA of mouse gene znf230 was cloned by rapid amplification of cDNA ends
      (RACE). This cDNA is 982 base pairs (bp) in length and encodes a 230 amino acids
      (aa) protein with a ring finger domain at its C-terminus. Ninety-one and 98%
      nucleotide (nt) and aa sequence identity are observed with its human homolog.
      Revealed by Northern blot and reverse transcriptase-polymerase chain reaction (RT
      PCR), this cDNA is only detected in testicular tissue, whereas the longer
      transcripts of 2.4 and 4.4kb are ubiquitously expressed. The expression of znf230
      in testis is developmentally regulated and first detected at day 6 postnatal
      (pn). It reaches adult level between day 14 and 21 pn during which round
      spermatids appear in seminiferous tubule. The protein of znf230 exhibits DNA
      binding activity and its ring finger domain may function as an activator module
      in transcription. Therefore, it is postulated that znf230 may function as a
      testis specific transcription factor during mouse spermatogenesis.

PMID- 12804570
TI  - PprI: a general switch responsible for extreme radioresistance of Deinococcus
      radiodurans.
AB  - Deinococcus radiodurans exhibits an extraordinary ability to withstand the lethal
      and mutagenic effects of DNA damaging agents, particularly, ionizing radiation.
      Available evidence indicates that efficient repair of DNA damage and protection
      of the chromosomal structure are mainly responsible for the radioresistance.
      Little is known about the biochemical basis for this phenomenon. We have
      identified a unique gene, pprI, as a general switch for downstream DNA repair and
      protection pathways, from a natural mutant, in which pprI is disrupted by a
      transposon. Complete functional disruption of the gene in wild-type leads to
      dramatic sensitivity to ionizing radiation. Radioresistance of the disruptant
      could be fully restored by complementation with pprI. In response to radiation
      stress, PprI can significantly and specifically induce the gene expression of
      recA and pprA and enhance the enzyme activities of catalases. These results
      strongly suggest that PprI plays a crucial role in regulating multiple DNA repair
      and protection pathways in response to radiation stress.

PMID- 12804571
TI  - Formate increases the F0F1-ATPase activity in Escherichia coli growing on glucose
      under anaerobic conditions at slightly alkaline pH.
AB  - Escherichia coli growing on glucose under anaerobic conditions at slightly
      alkaline pH carries out a mixed-acid fermentation resulting in the production of
      formate among the other products that can be excreted or further oxidized to H(2)
      and CO(2). H(2) production is largely dependent on formate dehydrogenase H and
      hydrogenases 3 and 4 constituting two formate hydrogen lyases, and on the
      F(0)F(1)-ATPase. In this study, it has been shown that formate markedly increased
      ATPase activity in membrane vesicles. This activity was significantly (1.8-fold)
      stimulated by 100mM K(+) and inhibited by N,N(')-dicyclohexylcarbodiimide and
      sodium azide. The increase in ATPase activity was absent in atp, trkA, and hyf
      but not in hyc mutants. ATPase activity was also markedly increased by formate
      when bacteria were fermenting glucose with external formate (30mM) in the growth
      medium. However this activity was not stimulated by K(+) and absent in atp and
      hyc but not in hyf mutants. The effects of formate on ATPase activity disappeared
      when cells were performing anaerobic (nitrate/nitrite) or aerobic respiration.
      These results suggest that the F(0)F(1)-ATPase activity is dependent on K(+)
      uptake TrkA system and hydrogenase 4, and on hydrogenase 3 when cells are
      fermenting glucose in the absence and presence of external formate, respectively.

PMID- 12804572
TI  - A novel membrane-bound Ech [NiFe] hydrogenase in Desulfovibrio gigas.
AB  - In the present study, we report the identification of an operon with six coding
      regions for a multisubunit membrane-bound [NiFe] hydrogenase in the genome of
      Desulfovibrio gigas. Sequence analysis of the deduced polypeptides reveals a high
      similarity to subunits of proteins belonging to the family of Ech hydrogenases.
      The operon is organised similarly to the operon coding for the Ech hydrogenase
      from Methanosarcina barkeri, suggesting that both encode very similar
      hydrogenases. Expression of the operon was detected by Northern blot and RT-PCR
      analyses, and the presence of the encoded proteins was examined by Western
      blotting. The possible role of this hydrogenase is discussed, relating it with a
      potential function in the H(2) cycling as a mechanism for energy conservation in
      D. gigas. The present study provides therefore valuable insights into the open
      question of the energy conserving mechanism in D. gigas.

PMID- 12804573
TI  - Specific strychnine binding sites on acrosome-associated membranes of golden
      hamster spermatozoa.
AB  - This study demonstrates for the first time, that membrane vesicles originated
      from the hamster sperm head after the occurrence of the acrosome reaction,
      possess specific strychnine binding sites. [3H]Strychnine binding was saturable
      and reversible, being displaced by unlabeled strychnine (IC(50)=26.7+/-2.3
      microM). Kinetic analysis revealed one binding site with K(d)=120nM and
      B(max)=142fmol/10(6) spermatozoa. Glycine receptor agonists beta-alanine and
      taurine inhibited strychnine binding by 20-30%. Surprisingly, glycine stimulated
      binding by about 40-50%. Results obtained in this study strongly suggest the
      presence of glycine receptors-with distinctive kinetic properties on the
      periacrosomal plasma membrane of hamster spermatozoa. Localization of this
      receptor fits well with its previously proposed role in acrosomal exocytosis
      during mammalian fertilization.

PMID- 12804574
TI  - Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin
      linked kinase and cyclic nucleotide-dependent protein kinases.
AB  - Protein phosphatases play key roles in cellular regulation and are subjected to
      control by protein inhibitors whose activity is in turn regulated by
      phosphorylation. Here we investigated the possible regulation of phosphorylation
      dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI,
      by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at
      the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited
      the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase
      holoenzyme (MPH) with IC(50) values of 1-8 nM. PKA predominantly phosphorylated a
      site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective.
      Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased
      inhibition of PP1c (IC(50)=0.1 nM) and MPH (IC(50)=8 nM). These results suggest
      that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct
      kinases and signaling pathways.

PMID- 12804575
TI  - Characterisation of recombinant HERG K+ channel blockade by the Class Ia
      antiarrhythmic drug procainamide.
AB  - Class Ia antiarrhythmic drugs, including procainamide (PROC), are associated with
      cardiac sodium channel blockade, delayed ventricular repolarisation and with a
      risk of ventricular pro-arrhythmia. The HERG K(+) channel is frequently linked to
      drug-induced pro-arrhythmia. Therefore, in this study, interactions between PROC
      and HERG K(+) channels were investigated, with particular reference to potency
      and mechanism of drug action. Whole-cell patch-clamp recordings of HERG current
      (I(HERG)) were made at 37 degrees C from human embryonic kidney (HEK 293) cells
      stably expressing the HERG channel. Following activating pulses to +20 mV,
      I(HERG) tails were inhibited by PROC with an IC(50) value of approximately 139
      microM. I(HERG) blockade was found to be both time- and voltage-dependent,
      demonstrating contingency upon HERG channel gating. However, I(HERG) inhibition
      by PROC was relieved by depolarisation to a highly positive membrane potential
      (+80 mV) that favoured HERG channel inactivation. These data suggest that PROC
      inhibits the HERG K(+) channel by a primarily 'open' or 'activated' channel state
      blocking mechanism and that avidity of drug-binding is decreased by extensive
      I(HERG) inactivation. The potency of I(HERG) blockade by PROC is much lower than
      for other Class Ia agents that have been studied previously under analogous
      conditions (quinidine and disopyramide), although the blocking mechanism appears
      similar. Thus, differences between the chemical structure of PROC and other Class
      Ia antiarrhythmic drugs may help provide insight into chemical determinants of
      blocking potency for agents that bind to open/activated HERG channels.

PMID- 12804576
TI  - AKAP7gamma is a nuclear RI-binding AKAP.
AB  - Spatial regulation of protein kinase A (PKA) is accomplished by its sequestration
      via A-kinase anchor proteins (AKAPs). PKA activity is critical for mammalian
      oocyte development, suggesting that PKA must be appropriately positioned in these
      large cells. A screen for AKAPs in oocytes identified AKAP7gamma, an AKAP
      originally found in pancreas. Yeast two-hybrid analysis and co
      immunoprecipitation studies showed that AKAP7gamma bound the type I PKA
      regulatory subunit (RI) and that the RI-binding domain overlapped the previously
      identified type II PKA regulatory subunit (RII) binding domain. Overexpressed
      AKAP7gamma localized to the nuclei of HEK 293 cells via a nuclear localization
      signal. In addition, endogenous AKAP7gamma protein was found in both the nucleus
      and cytoplasm of oocytes. This work identifies AKAP7gamma as the first nuclear
      AKAP to bind RI and suggests that AKAP7gamma may be responsible for positioning
      PKA via RI and/or RII to regulate PKA-mediated gene transcription in both somatic
      cells and oocytes.

PMID- 12804577
TI  - Sugars regulate sucrose transporter gene expression in citrus.
AB  - We report the isolation and characterization of two sucrose transporter cDNAs
      (CitSUT1 and CitSUT2) from citrus. CitSUT1 and CitSUT2 encode putative proteins
      (CitSUT1 and CitSUT2) of 528 and 607 amino acids, respectively. CitSUT1 and
      CitSUT2 share high similarities with sucrose transporters isolated from other
      plants. The expression of CitSUT1 in mature leaf discs is repressed by exogenous
      sucrose, glucose, mannose, and the glucose analog 2-deoxyglucose but not by
      another glucose analog 3-O-methylglucose, indicating a hexokinase (HXK)-mediated
      signaling pathway. CitSUT2 expression is not affected by exogenous sugars.
      Whereas CitSUT1 expresses strongly in source, sugar exporting organs, CitSUT2
      expresses more strongly in sink, sugar importing organs, suggesting different
      physiological roles for these sucrose transporters.

PMID- 12804578
TI  - A common periodic table of codons and amino acids.
AB  - A periodic table of codons has been designed where the codons are in regular
      locations. The table has four fields (16 places in each) one with each of the
      four nucleotides (A, U, G, C) in the central codon position. Thus, AAA (lysine),
      UUU (phenylalanine), GGG (glycine), and CCC (proline) were placed into the
      corners of the fields as the main codons (and amino acids) of the fields. They
      were connected to each other by six axes. The resulting nucleic acid periodic
      table showed perfect axial symmetry for codons. The corresponding amino acid
      table also displaced periodicity regarding the biochemical properties (charge and
      hydropathy) of the 20 amino acids and the position of the stop signals. The table
      emphasizes the importance of the central nucleotide in the codons and predicts
      that purines control the charge while pyrimidines determine the polarity of the
      amino acids. This prediction was experimentally tested.

PMID- 12804579
TI  - ATP-binding is stabilized by a stacking interaction within the binding site of
      Na+/K+ -ATPase.
AB  - Site-directed mutagenesis was applied to modify phenylalanines (Phe(475)Trp,
      Phe(548)Tyr, and both) to generate mutants on the basis of molecular modeling of
      the ATP-binding domain of Na(+)/K(+)-ATPase, in order to characterize the forces
      that stabilize ATP in its binding pocket. Each of the mutants was examined by
      Raman difference spectroscopy, i.e., as a difference between the spectrum of the
      domain with and without bound ATP. It was shown that Phe(475) plays a key role in
      stabilizing ATP-binding by a stacking interaction. Phe(548) co-stabilizes ATP on
      the opposite site of the binding pocket and its type of interaction with ATP
      binding differs from that of Phe(475).

PMID- 12804580
TI  - DNA uptake and repair enzyme access to transfected DNA is under reported by gene
      expression.
AB  - Gene expression is the typical biological end point of interest following
      transfection. However, transcription may not accurately assess DNA uptake, or the
      ability of transfected DNA to be acted on by other enzymatic pathways. We have
      compared DNA uptake to gene expression and the unrelated enzymatic process of DNA
      double strand break (DSB) repair. Transfection efficiency (at limiting DNA
      concentration) was assessed as a function of DNA uptake and gene expression in
      the DSB repair proficient WI38VA13 and MO59K cell lines and the DSB repair
      defective cell line MO59J, by comparing eGFP expression from the pHygEGFP
      expression vector with uptake of rhodamine labeled linear pSP189 plasmid (3:1).
      Repair proficient cells expressed eGFP most efficiently, but never approached DNA
      uptake levels (>or=90%). Although transfected DNAs were stable in repair
      proficient cells and degraded in MO59J cells, most cells did not express eGFP,
      but in the repair proficient cells linear DNA did undergo DSB repair.

PMID- 12804581
TI  - The contribution of the SPCA1 Ca2+ pump to the Ca2+ accumulation in the Golgi
      apparatus of HeLa cells assessed via RNA-mediated interference.
AB  - The secretory-pathway Ca(2+)-ATPase SPCA1 is a thapsigargin-insensitive
      intracellular Ca(2+) pump found mostly in the Golgi compartment. We have explored
      the contribution of this Ca(2+) pump to cytosolic Ca(2+) signaling in HeLa cells
      by using RNA-mediated interference to disrupt its expression. Removal of SPCA1
      was confirmed by immunofluorescence with specific anti-SPCA1 antibodies.
      Measurements of the free Ca(2+) concentration in the lumen of the Golgi apparatus
      by specifically targeting the Ca(2+)-sensitive luminescent protein aequorin to
      this organelle revealed that endogenous SPCA1 was responsible for Ca(2+) uptake
      in a subfraction of the Golgi apparatus. HeLa cells lacking SPCA1 could still set
      up baseline Ca(2+) spiking when stimulated with histamine, indicating that the
      SPCA1-containing Ca(2+) store was not absolutely needed to set up these
      oscillations. However, baseline Ca(2+) oscillations occurred less frequently than
      in control cells, pointing to a contribution of SPCA1 in the shaping of the
      cytosolic Ca(2+) signal in HeLa cells.

PMID- 12804583
TI  - Global analysis of differentially expressed genes in oxidized LDL-treated human
      aortic smooth muscle cells.
AB  - Oxidized low density lipoproteins (OxLDL) play a key role in atherogenesis and
      induce a wide range of biological effects on smooth muscle cells. We used two
      commercially available cDNA microarray systems with a total of 35,932 human genes
      to determine differentially expressed genes in OxLDL-treated human aortic smooth
      muscle cells (HASMC) and to identify novel genes responsive to this agonist. We
      found a significant increase in expression of 180 and a significant decrease in
      expression of 192 named genes after treatment by OxLDL, compared with native LDL.
      Real time-PCR analysis confirmed microarray data for seven of eight tested genes.
      The differentially regulated genes were grouped into 16 classes based on the
      functions of the corresponding protein products. Our data demonstrate that OxLDL
      predominantly elevates expression of genes involved in cell-cell interactions,
      membrane transport, oncogenesis, apoptosis, and transcription and decreases
      expression of genes responsible for protein and nucleic acid biosynthesis, lipid
      metabolism, and humoral responses. Interestingly, we identify for the first time
      expression of metastasis-related protein (MB2) and novel scavenger receptor SREC
      II in HASMC and these were upregulated 12- and 3-fold by OxLDL treatment,
      respectively. These findings have major implications for understanding
      atherogenic effect of OxLDL.

PMID- 12804582
TI  - Molecular identification of the first insect proctolin receptor.
AB  - The website of the Drosophila Genome Project (www.flybase.org) contains the
      sequence of an annotated gene CG6986, which is predicted to code for a G protein
      coupled receptor. We cloned the cDNA of this gene and expressed it in Chinese
      hamster ovary cells. Screening of a neuropeptide library revealed that the
      expressed receptor was specific for the neuropeptide proctolin (EC(50), 6x10(
      10)M). Proctolin (RYLPT) was the first invertebrate neuropeptide to be fully
      sequenced (already in 1975) and occurs with identical structure in both
      crustaceans and insects, where it has myo- and neurostimulatory actions. Northern
      blots showed that the Drosophila proctolin receptor was only weakly expressed in
      embryos, larvae, pupae, and in the thoraces and abdomina of adult flies, but
      strongly in the heads of adult animals. The Drosophila receptor reported here is
      the first invertebrate proctolin receptor to be identified.

PMID- 12804584
TI  - The pore region of the Kv1.2alpha subunit is an important component of
      recombinant Kv1.2 channel oxygen sensitivity.
AB  - Oxygen-sensitive K(+) channels are important elements in the cellular response to
      hypoxia. Although much progress has been made in identifying their molecular
      composition, the structural components associated to their O(2)-sensitivity are
      not yet understood. Recombinant Kv1.2 currents expressed in Xenopus oocytes are
      inhibited by a decrease in O(2) availability. On the contrary, heterologous Kv2.1
      channels are O(2)-insensitive. To elucidate the protein segment responsible for
      the O(2)-sensitivity of Kv1.2 channels, we analyzed the response to anoxia of
      Kv1.2/Kv2.1 chimeric channels. Expression of chimeric Kv2.1 channels each
      containing the S4, the S1-S3 or the S6-COOH segments of Kv1.2 polypeptide
      resulted in a K(+) current insensitive to anoxia. In contrast, transferring the
      S5-S6 segment of Kv1.2 into Kv2.1 produced an O(2)-sensitive K(+) current.
      Finally, mutating a redox-sensitive methionine residue (M380) of Kv1.2
      polypeptide did not affect O(2)-sensitivity. Thus, the pore and its surrounding
      regions of Kv1.2 polypeptide confer its hypoxic inhibition. This response is
      independent on the redox modulation of methionine residues in this protein
      segment.

PMID- 12804585
TI  - Ischemia-reperfusion alters gene expression of Na+-K+ ATPase isoforms in rat
      heart.
AB  - The present study investigated whether oxidative stress plays a role in ischemia
      reperfusion-induced changes in cardiac gene expression of Na(+)-K(+) ATPase
      isoforms. The levels of mRNA for Na(+)-K(+) ATPase isoforms were assessed in the
      isolated rat heart subjected to global ischemia (30 min) followed by reperfusion
      (60 min) in the presence or absence of superoxide dismutase (5 x 10(4)U/L) plus
      catalase (7.5 x 10(4)U/L), an antioxidant mixture. The levels of mRNA for the
      alpha(2), alpha(3), and beta(1) isoforms of Na(+)-K(+) ATPase were significantly
      reduced in the ischemia-reperfusion hearts, unlike the alpha(1) isoform.
      Pretreatment with superoxide dismutase+catalase preserved the ischemia
      reperfusion-induced changes in alpha(2), alpha(3), and beta(1) isoform mRNA
      levels of the Na(+)-K(+) ATPase, whereas the alpha(1) mRNA levels were
      unaffected. In order to test if oxidative stress produced effects similar to
      those seen with ischemia-reperfusion, hearts were perfused with an oxidant,
      H(2)O(2) (300 microM), or a free radical generator, xanthine (2mM) plus xanthine
      oxidase (0.03 U/ml) for 20 min. Perfusion of hearts with H(2)O(2) or
      xanthine/xanthine oxidase depressed the alpha(2), alpha(3), and beta(1) isoform
      mRNA levels of the Na(+)-K(+) ATPase, but had lesser effects on alpha(1) mRNA
      levels. These results indicate that Na(+)-K(+) ATPase isoform gene expression is
      altered differentially in the ischemia-reperfusion hearts and that antioxidant
      treatment appears to attenuate these changes. It is suggested that alterations in
      Na(+)-K(+) ATPase isoform gene expression by ischemia-reperfusion may be mediated
      by oxidative stress.

PMID- 12804586
TI  - Dynamic regulation of alternative ATP-binding cassette transporter A1
      transcripts.
AB  - The ATP-binding cassette transporter A1 (ABCA1) gene, a major regulator of high
      density lipoprotein (HDL) metabolism, utilizes several transcriptional start
      sites. The pattern of transcripts among tissues and cells differed significantly.
      The longest (class 1) transcripts were abundant in adult brain and fetal tissues.
      Class 2 transcripts predominated in most other tissues. The shortest (class 3)
      transcripts were present mainly in adult liver and lung. To study the biochemical
      significance of changes in transcript distribution, two cell models were
      compared. In primary human fibroblasts, upregulation of mRNA levels by oxysterols
      and retinoic acid increased the relative proportion of class 2 transcript
      compared to class 1. Phorbol ester stimulated human macrophage-derived THP-1
      cells increased the abundance of class 1 transcripts relative to class 2. In both
      cell lines class 3 transcript levels were minimal and unchanged. It is shown here
      for the first time that the regulation of ABCA1 mRNA levels exploits the use of
      alternative transcription start sites.

PMID- 12804587
TI  - Increased thioredoxin-1 inhibits SSAT expression in MCF-7 human breast cancer
      cells.
AB  - Spermidine/spermine N(1)-acetyltransferase (SSAT) regulates polyamine catabolism.
      Thioredoxin-1 (Trx-1) is a redox protein that is overexpressed in human cancer
      leading to increased cell proliferation, decreased apoptosis, and decreased
      patient survival. We report that SSAT mRNA expression is decreased in Trx-1
      transfected MCF-7 human breast cancer cells. There is also a decrease in SSAT
      enzyme activity and lower putrescine levels but no change in spermine or
      spermidine levels. The expression of SSAT is regulated by the NF-E2-related
      factor 2 (Nrf-2) and polyamine modulated factor-1 (PMF-1) transcription factor
      complex. Trx-1 transfected MCF-7 cells showed decreased Nrf-2/PMF-1 DNA binding
      without a change in Nrf-2 or PMF-1 protein expression. The results suggest that
      Trx-1 may play a role in the redox regulation of SSAT expression and polyamine
      homeostasis that could contribute to the biological effects of Trx-1.

PMID- 12804588
TI  - Effect of hybrid complement regulatory proteins on xenogeneic cells.
AB  - To suppress C3 fragment deposition in the classical pathway complement activation
      on xenogeneic membranes, decay accelerating factor (DAF) was the most effective
      molecule among the complement regulatory proteins (CRPs) used in the present
      study. C3 fragment deposition was closely related to subsequent xenogeneic cell
      lysis. However, other molecules were also very effective in different ways and
      include phosphatidylinositol (PI)-anchored short consensus repeat (SCR) 2-4 of
      membrane cofactor protein (MCP-PI), PI-anchored C1 esterase inhibitor (C1-INH
      PI), and PI-anchored SCR8-11 of complement receptor type 1 (CR1-PI). On the other
      hand, regarding a strategy for downregulating C4 fragment deposition, the use of
      only C1-INH-PI and PI-anchored SCR1-3 of the C4b-binding protein (C4bp-PI) was
      found to be effective.

PMID- 12804589
TI  - Selective repression of c-fos gene transcription in rat embryo fibroblasts
      transformed by oncogenes E1A and cHa-ras.
AB  - Transformation of REF cells by oncogenes E1A and cHa-ras leads to activation of
      AP-1 factor concomitantly with down-regulation of c-fos gene transcription. Here
      we addressed two issues: (i) how does transcription of Fos/Jun-regulated genes
      change in the cells lacking Fos-Jun heterodimers; (ii) to which extent HDAC
      mediated chromatin reorganization does affect, apart from c-fos, transcription of
      some other early and late-response genes. To this end, we studied the kinetics of
      serum-stimulated transcription of c-fos, c-jun, fra-1, egr-1, and cyclinD1 genes,
      as well as the effects of sodium butyrate, an inhibitor of histone deacetylase
      activity, on transcription of these genes in normal REF cells and transformants
      E1A+ras.

PMID- 12804590
TI  - Coffee diterpenes prevent benzo[a]pyrene genotoxicity in rat and human culture
      systems.
AB  - The coffee-specific diterpenes cafestol and kahweol (C+K) have been identified as
      two important chemoprotective agents in coffee. In the present study, the
      potential preventive effects of C+K against the genotoxicity of B[a]P were
      investigated in rat primary hepatocytes and in human bronchial Beas-2B cells.
      Several independent mechanisms were identified and their respective contribution
      to the overall protective effects was determined. A marked dose-dependent
      inhibition by C+K of B[a]P DNA-binding was found in cells of both origins.
      However, data showed that the significant induction by C+K of the detoxifying
      enzyme GST-Yp subunit is the key mechanism of protection against B[a]P DNA
      binding in rat liver. In contrast, the phase I-mediated mechanism where C+K
      produce an inhibition of CYP 1A1 induction by B[a]P is of key significance for
      the C+K protection in human Beas-2B cells. Moreover, this effect suggests a novel
      mechanism of chemoprotection by the coffee diterpenes cafestol and kahweol.

PMID- 12804591
TI  - A melittin-related peptide from the skin of the Japanese frog, Rana tagoi, with
      antimicrobial and cytolytic properties.
AB  - Two peptides with antimicrobial and cytolytic properties were purified from an
      extract of the skin of Tago's brown frog Rana tagoi. The primary structure of one
      peptide (FLPILGKLLS(10)GIL.NH(2)) identifies it as a member of the temporin
      family, whereas the second peptide (AIGSILGALA(10)KGLPTLISWI(20)KNR.NH(2))
      displays 78% sequence identity to melittin from the venom of the honeybee Apis
      florea. Compared with melittin, the melittin-related peptide (MRP) was equipotent
      in inhibiting the growth of the Gram-positive bacterium Staphylococcus aureus, 5
      fold less potent against the Gram-negative bacterium Escherichia coli and against
      the fungal pathogen, Candida albicans. MRP was 13-fold less hemolytic than
      melittin against human erythrocytes and 4- and 5-fold less cytolytic against
      mouse EL4 T-lymphoma-derived cells and L929 fibroblasts, respectively. However,
      at non-cytotoxic concentrations (<or=8 microM), MRP did not protect HeLa cells
      from cell death produced by human rhinovirus type 2 infection.

PMID- 12804592
TI  - Acetylation of histone H3 at lysine 9 by ethanol in rat hepatocytes.
AB  - Histone acetylation plays an important role in transcriptional activation. We
      have investigated the effect of ethanol on nuclear histone H3 acetylation in rat
      hepatocytes. Hepatocytes were incubated with ethanol (5-200 mM) for 24h and then
      acetylation states of nuclear histone H3 at specific lysine residues (Lys(9) and
      Lys(14)) were measured by immunoblot analysis using site-specific antibodies.
      Ethanol increased acetylation of histone H3 at Lys(9) in a dose-dependent manner;
      3-fold at 5mM and maximum of 8-fold at 100mM. Sensitivity to low dose of ethanol
      was remarkable. This ethanol-induced acetylation was also time-dependent, showing
      a maximal response at 24h. Ethanol did not alter the level of histone H3
      expression. Trichostatin A, a histone deacetylase inhibitor, was used as a
      positive control and it also increased acetylation. However, acetylation at
      Lys(14) was not affected by ethanol. Treatment of cells with ethanol metabolizing
      enzyme inhibitors (4-methylpyrazole and cyanamide) decreased ethanol-induced
      histone H3 acetylation at Lys(9). This is the first report of ethanol-induced
      selective, post-translational acetylation of histone H3 at Lys(9). This is not
      due to increased histone expression or a direct physical effect of ethanol but is
      dependent on ethanol metabolism.

PMID- 12804593
TI  - Measurement of acetylcholine-induced endothelium-derived nitric oxide in aorta
      using a newly developed catheter-type nitric oxide sensor.
AB  - Intra-aortic measurement of nitric oxide (NO) would provide valuable insights
      into NO bioavailability in systemic circulation and vascular endothelial
      function. In the present study, we thus developed a catheter-type NO sensor to
      measure intra-aortic NO concentration in vivo. An NO sensor was encased and fixed
      in a 4-Fr catheter. The sensor was then located in the thoracic aorta via the
      femoral artery through a 7-Fr catheter to measure intra-aortic plasma NO
      concentration in vivo in anesthetized dogs. Infusion of acetylcholine (10
      microg/kg) increased base-to-peak plasma NO level in the aorta by 2.4+/-0.4 nM
      (n=7). After 20-min infusion of N(G)-methyl-L-arginine (NO synthase inhibitor),
      changes in plasma NO concentration in response to acetylcholine were attenuated
      significantly (1.8+/-0.4 nM, P<0.003, n=7). In conclusion, the newly developed
      catheter-type NO sensor successfully measured acetylcholine-induced changes in
      intra-aortic plasma concentration of endothelium-derived NO in vivo and
      demonstrated applicability to direct evaluation of intravascular NO
      bioavailability.

PMID- 12804594
TI  - Mechanism of xanthine oxidase catalyzed biotransformation of HMX under anaerobic
      conditions.
AB  - Enzyme catalyzed biotransformation of the energetic chemical octahydro-1,3,5,7
      tetranitro-1,3,5,7-tetrazocine (HMX) is not known. The present study describes a
      xanthine oxidase (XO) catalyzed biotransformation of HMX to provide insight into
      the biodegradation pathway of this energetic chemical. The rates of
      biotransformation under aerobic and anaerobic conditions were 1.6+/-0.2 and
      10.5+/-0.9 nmolh(-1)mgprotein(-1), respectively, indicating that anaerobic
      conditions favored the reaction. The biotransformation rate was about 6-fold
      higher using NADH as an electron-donor compared to xanthine. During the course of
      reaction, the products obtained were nitrite (NO(2)(-)), methylenedinitramine
      (MDNA), 4-nitro-2,4-diazabutanal (NDAB), formaldehyde (HCHO), nitrous oxide
      (N(2)O), formic acid (HCOOH), and ammonium (NH(4)(+)). The product distribution
      gave carbon and nitrogen mass-balances of 91% and 88%, respectively. A
      comparative study with native-, deflavo-, and desulfo-XO and the site-specific
      inhibition studies showed that HMX biotransformation occurred at the FAD-site of
      XO. Nitrite stoichiometry revealed that an initial single N-denitration step was
      sufficient for the spontaneous decomposition of HMX.

PMID- 12804595
TI  - Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53
      dependent apoptosis.
AB  - The objective of this study was to characterize the apoptotic pathways activated
      by fast neutrons in the human lymphoblastoid cell line TK6 and in its p53 -/-
      derivative. Our results demonstrate that while p53 is not required for neutron
      induced apoptosis, as previously shown, it does affect the kinetics of apoptosis
      and the molecular pathways leading to the activation of effector caspases.
      Indeed, rapid p53-dependent apoptosis was associated with the activation of
      caspase 9, 8, 3, and 7 and the cleavage of BID by caspase 8. In contrast, the
      slow-occurring p53-independent apoptotic process, mediated by caspase 7, took
      place without BID cleavage and loss of transmembrane mitochondrial potential.
      Altogether, our findings highlight an essential role for caspase 8-mediated BID
      cleavage, in the course of p53-dependent apoptosis triggered by fast neutrons in
      lymphoid cells. They also demonstrate that this mechanism is not involved in p53
      independent apoptosis.

PMID- 12804596
TI  - The regulating effect of heme oxygenase/carbon monoxide on hypoxic pulmonary
      vascular structural remodeling.
AB  - Hypoxic pulmonary vascular structural remodeling (HPVSR) is the important
      pathologic basis of hypoxic pulmonary hypertension (HPH). The discoveries of
      endogenous gaseous messenger molecules, nitric oxide (NO) and carbon monoxide
      (CO), have been moving the research of HPVSR to a very new phase. But the effect
      and significance of heme oxygenase (HO)/CO on the development of HPVSR have not
      been fully understood. In this study, we observed the alteration of endogenous
      HO/CO system in five time points during 14 days and found that the content of CO
      in lung homogenates in rats with HPVSR increased in a time-dependent double-peak
      manner. Exogenous supply of ZnPP-IX, an inhibitor of HO-1, decreased the content
      of CO in lung homogenate, decreased the expression of Fas and apoptotic cells in
      pulmonary artery smooth muscle cells (PASMCs), up-regulated the expression of
      PCNA in PASMCs, and worsened HPH and HPVSR of hypoxic rats. Meanwhile, exogenous
      supply of CO played an adverse action. The results showed that the up-regulation
      of HO/CO exerted a protective role in the development of HPVSR.

PMID- 12804597
TI  - Characterization of quercetin binding site on DNA gyrase.
AB  - Gyrases are DNA topology modifying enzymes present only in prokaryotes which
      makes them an attractive target for antibacterial drugs. Quercetin, one of the
      most abundant natural flavonoids, inhibits supercoiling activity of bacterial
      gyrase and induces DNA cleavage. It has been generally assumed that the mechanism
      of flavonoid inhibition is based on interaction with DNA. We show that quercetin
      binds to the 24 kDa fragment of gyrase B of Escherichia coli with a K(D) value of
      15 microM and inhibits ATPase activity of gyrase B. Its binding site overlaps
      with ATP binding pocket and could be competitively replaced by either ATP or
      novobiocin. The structural model of quercetin-gyrase complex was prepared, based
      on the close similarity with ATP and quercetin binding sites of the src family
      tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two
      different mechanisms based either on interaction with DNA or with ATP binding
      site of gyrase.

PMID- 12804599
TI  - Oligomerization of adenosine A2A and dopamine D2 receptors in living cells.
AB  - We investigated whether oligomerization of adenosine A(2A) receptor (A(2A)R) and
      dopamine D(2) receptor (D(2)R) exists in living cells using modified
      bioluminescence resonance energy transfer (BRET(2)) technology. Fusion of these
      receptors to a donor, Renilla luciferase (Rluc), and to an acceptor, modified
      green fluorescent protein (GFP(2)), did not affect the ligand binding affinity,
      subcellular distribution, and coimmunoprecipitation of the receptors. BRET was
      detected not only between Myc-D(2)R-Rluc and A(2A)R-GFP(2) but also between HA
      tagged A(2A)R-Rluc and A(2A)R-GFP(2). These results indicate A(2A)R, either
      homomeric or heteromeric with D(2)R, exists as an oligomer in living cells.

PMID- 12804598
TI  - APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes
      impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human
      prostate cancer cell line.
AB  - We have found a novel alternative splicing product of the apoptotic protease
      activating factor 1 (APAF-1), termed APAF-1-ALT, in the LNCaP human prostate
      cancer cell line. APAF-1-ALT harbors the caspase recruitment domain and an
      incomplete CED-4 like/ATPase domain, but lacks the WD-40 repeat units. The LNCaP
      cell expressed the full-length APAF-1 weakly and APAF-1-ALT rather abundantly,
      especially after mycoplasma infection. LNCaP underwent a retarded DNA damage
      induced apoptosis, which was independent of caspase 9 activity. APAF-1-ALT
      functioned less effectively in inducing apoptosis than did APAF-1-XL, the full
      length APAF-1, in transient transfection. Moreover, APAF-1-ALT interfered with
      APAF-1-XL's ability to induce apoptosis in transient double transfection
      experiment. These results indicate that APAF-1-ALT is a molecule that is
      deficient and impeded for mediating apoptosis and that it may contribute to the
      resistance to DNA damage-induced treatment observed in LNCaP.

PMID- 12804600
TI  - Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ 
      ATPase2a and phospholamban in the human heart.
AB  - The Ca(2+)-binding S100A1 protein displays a specific and high expression level
      in the human myocardium and is considered to be an important regulator of heart
      contractility. Diminished protein levels detected in dilated cardiomyopathy
      possibly contribute to impaired Ca(2+) handling and contractility in heart
      failure. To elucidate the S100A1 signaling pathway in the human heart, we
      searched for S100A1 target proteins by applying S100A1-specific affinity
      chromatography and immunoprecipitation techniques. We detected the formation of a
      Ca(2+)-dependent complex of S100A1 with SERCA2a and PLB in the human myocardium.
      Using confocal laser scanning microscopy, we showed that all three proteins co
      localize at the level of the SR in primary mouse cardiomyocytes and confirmed
      these results by immunoelectron microscopy in human biopsies. Our results support
      a regulatory role of S100A1 in the contraction-relaxation cycle in the human
      heart.

PMID- 12804601
TI  - Establishment and functional validation of a structural homology model for human
      DNA methyltransferase 1.
AB  - Changes in DNA methylation patterns play an important role in tumorigenesis. The
      DNA methyltransferase 1 (DNMT1) protein represents a major DNA methyltransferase
      activity in human cells and is therefore a prominent target for experimental
      cancer therapies. However, there are only few available inhibitors and their high
      toxicity and low specificity have so far precluded their broad use in
      chemotherapy. Based on the strong conservation of catalytic DNA methyltransferase
      domains we have used a homology modeling approach to determine the three
      dimensional structure of the DNMT1 catalytic domain. Our results suggest an
      overall structural conservation with other DNA methyltransferases but also
      indicate local conformational differences. To prove the validity of our model we
      used it as a template to design a novel derivative of the known DNA
      methyltransferase inhibitor 5-azacytidine. The resulting compound (N4
      fluoroacetyl-5-azacytidine) functioned as an efficient inhibitor of DNA
      methylation in human tumor cell lines and also provides novel opportunities for
      pharmacological applications.

PMID- 12804602
TI  - Identification of higher plant GlsA, a putative morphogenesis factor of gametic
      cells.
AB  - GlsA has been identified in an asexual-reproductive-cell (gonidia)-deficient
      mutant of Volvox as a chaperone-like protein essential for gonidia production. In
      this study, we isolated an angiosperm glsA (LlglsA) gene expressed during Lilium
      longiflorum pollen development. Immunoblot analyses showed that the strong LlGlsA
      expression occurred in the generative cell and its pattern during pollen
      development corresponded to that of alpha-tubulin. Morphological analyses
      succeeded in visualizing the dispersion of the strong LlGlsA signal in developing
      generative cells. In addition, multiple-immunofluorescence staining of LlGlsA and
      alpha-tubulin revealed that some of the dot-like LlGlsA signals were co-localized
      with microtubule filaments. From those results, we suggest that angiosperm GlsA
      functions as a chaperone modifying various structures during male gametic cell
      formation.

PMID- 12804603
TI  - Hydrogen peroxide-induced microsatellite instability in the Escherichia coli K-12
      endogenous tonB gene.
AB  - Damage to DNA by reactive oxygen species may be a significant source of
      endogenous mutagenesis in aerobic organisms. Using an endogenous tonB gene as a
      mutation selective marker in Escherichia coli, we have examined whether
      endogenous oxidative mutagenesis can contribute to genetic instability. We have
      also used oxyR(+) and oxyR(-) strains to evaluate how hydrogen peroxide
      scavenging system can contribute to genetic instability. The highest mutation
      frequency induced by hydrogen peroxide was 3.8x10(-6) at 600 microM and 5.3 x 10(
      6) at 40 microM in oxyR(+) and oxyR(-), respectively. Hydrogen peroxide induced
      minus frameshift mutations predominantly followed by transversions (G:C-->T:A,
      G:C-->C:G, and A:T-->T:A). The types and the nature of the mutations did not
      differ between strains. Frameshift mutations occurred at G:C and A:T sites
      equally, and in repeated and non-repeated sequences equally. It is evident that
      endogenous oxidative damage to DNA can increase the frequency of strand slippage
      intermediates occurring during DNA replication and contribute to genomic
      instability. Our results further indicate that oxyR regulon does not take part in
      the DNA-repair pathway against oxidative damage induced by hydrogen peroxide.

PMID- 12804604
TI  - Essential 110Cys in active site of membrane-associated prostaglandin E synthase
      2.
AB  - The amino acid sequence of membrane-associated prostaglandin (PG) E synthase-2
      (mPGE synthase-2), which has a broad specificity in its thiol requirement for a
      catalytic activity, has the consensus region from 104Leu to 120Leu found in
      glutaredoxin and of thioredoxin. The sequence of Cys-x-x-Cys in the consensus
      region is the active site for thioredoxin and mPGE synthase-2 also has this amino
      acid sequence (110Cys-x-x-113Cys). The mutation from 110Cys to Ser or the double
      mutation from 110Cys and 113Cys to Ser caused loss of PGE synthase activity,
      whereas the single mutation from 113Cys to Ser did not affect the enzyme
      activity. These results indicate that 110Cys, but not 113Cys, is the essential
      amino acid in the active site of mPGE synthase-2. 110Cys is an important amino
      acid in PGE synthase activity and plays the critical role as Cys at the same
      position in redoxin. Moreover, we found that the reduced form of lipoic acid
      (dihydrolipoic acid) serves as one of the natural activators of mPGE synthase-2
      in the cells.

PMID- 12804605
TI  - Solution structure and biological activity of recombinant salmon calcitonin S
      sulfonated analog.
AB  - Salmon calcitonin S-sulfonated analog (abbreviated as [S-SO(3)(-)]rsCT) was
      prepared by introducing two sulfonic groups into the side chains of Cys1 and Cys7
      of recombinant salmon calcitonin. The hypocalcemic potency of this open-chain
      analog is 5500IU/mg, which is about 30% higher than that (4500IU/mg) of the wild
      type. The solution conformation of [S-SO(3)(-)]rsCT was studied in aqueous
      trifluoroethanol solution by CD, 2D-NMR spectroscopy, and distance geometry
      calculations. In the mixture of 60% TFE and 40% water, the peptide assumes an
      amphipathic alpha-helix in the region of residues 4-22, which is one turn longer
      than that of the native sCT. The structural feature analysis of the peptide
      revealed the presence of hydrophobic surface composed of five hydrophobic side
      chains of residues Leu4, Leu9, Leu12, Leu16, and Leu19, and a network of salt
      bridges that consisted of a tetrad of oppositely charged side chains (Cys7-SO(3)(
      )-Lys11(+)-Glu15(-)-Lys18(+)). The multiple salt bridges resulted in the
      stabilization of the longer amphipathic alpha-helix. Meanwhile, the higher
      hypocalcemic potency of the peptide could be attributed to the array of
      hydrophobic side chains of five leucine residues of the amphipathic alpha-helix.

PMID- 12804606
TI  - Characterization of Drosophila nitric oxide synthase: a biochemical study.
AB  - The heme and flavin-binding domains of Drosophila nitric oxide synthase (DNOS)
      were expressed in Escherichia coli using the expression vector pCW. The denatured
      molecular mass of the expressed protein was 152kDa along with a proteolytically
      cleaved product of 121kDa. The DNOS heme protein exhibited very low
      Ca(2+)/calmodulin-dependent NO synthase activity. The trypsin digestion patterns
      were different from nNOS. The full-length DNOS protein had high degree of
      stability against trypsin. The activity assay of trypsin-digested protein
      confirmed the same result. Urea dissociation profile of DNOS full-length protein
      showed that the reductase domain activity was much more susceptible towards urea
      than the oxygenase domain activity. Urea gradient gel of DNOS full-length protein
      established distinct transition of dissociation and unfolding in the range 3-4M
      urea. Reductase domain activity of full-length DNOS protein against external
      electron acceptors like cytochrome c indicated slow electron transfer from FMN.
      The bacterial expression of DNOS full-length protein represents an important
      development in structure-function studies of this enzyme and comparison with
      other mammalian NOS enzymes which is evolutionary significant.

PMID- 12804607
TI  - PCR-based cloning of an intronless zebrafish no tail gene.
AB  - The zebrafish no tail gene (ntl) is indispensable for the formation of the
      notochord and tail structure. Here, we show the presence of an intronless ntl
      gene in zebrafish, which we designated cryptail (ctl). ctl could not be found in
      any zebrafish genomic resources examined and was only just cloned by a PCR-based
      approach that relied on its lack of introns and homology to ntl. The amplifiable
      region of ctl was confined to the transcribed region of ntl. ctl thus appeared to
      have been generated by reverse transcription of ntl mRNA, like a processed
      pseudogene. ctl was very polymorphic even in individual fish, but had no missense
      mutations. This may suggest that ctl has a physiological function in zebrafish.

PMID- 12804608
TI  - Fungal phyA gene expressed in potato leaves produces active and stable phytase.
AB  - Fungal phyA gene from Aspergillus ficuum (niger) was cloned and expressed in
      potato leaves. The recombinant enzyme was stable and catalytically active. The
      expressed protein in the leaves of the dicotyledonous plant retained most
      physical and catalytic properties of the benchmark A. ficuum phytase. The
      expressed enzyme was, however, 15% less glycosylated than the native phytase. The
      usual bi-hump pH optima profile, which is characteristic of the fungal phytase,
      was altered; however, the pH optimum at 5.0 was unchanged for phytate and at 4.0
      for synthetic substrate p-nitrophenyl phosphate. The temperature was, however,
      unchanged. The expressed phytase was found to be as sensitive as the native
      enzyme to the inhibitory action of pseudo substrate, myo-inositol hexasulfate,
      while losing about 90% of the activity at 20 microM inhibitor concentration.
      Similar to the benchmark phytase, the expressed phytase in leaves was completely
      inactivated by Arg modifier phenylglyoxal at 60 nM. In addition, the expressed
      phytase in the leaves was inhibited by antibody raised against a 20-mer internal
      peptide, which is present on the surface of the molecule as shown by the X-ray
      deduced 3D structure of fungal phytase. Taken together, the biochemical evidences
      indicate that fungal phytase when cloned and expressed in potato leaves produces
      a stable and active biocatalyst. 'Biofarming,' therefore, is an alternative way
      to produce functional hydrolytic enzymes as exemplified by the expression of A.
      ficuum (niger) phyA gene in potato leaf.

PMID- 12804609
TI  - Molecular interactions between STAT3 and protein inhibitor of activated STAT3,
      and androgen receptor.
AB  - STAT3 mainly acts as a signal transducer of IL-6 family cytokines and
      transcriptionally activates specific target genes. The recently discovered
      protein inhibitor of activated STAT3 (PIAS3) binds directly to STAT3 and blocks
      transcriptional activation. In our previous report, we demonstrated that PIAS3
      directly interacted with androgen receptor (AR) and affected AR-mediated gene
      activation. Furthermore, we also showed that AR associated with STAT3 and
      enhanced its activity. Here, we examined molecular interactions between STAT3,
      PIAS3, and AR to underline the mechanism of how they regulate each other. AR
      activation overcame the inhibitory effect on STAT3-mediated transcription by
      PIAS3. Co-immunoprecipitation experiments revealed that an active form of AR
      relieved STAT3 from STAT3-PIAS3 complex formation. These results indicate that AR
      and PIAS3 regulate the STAT3-mediated transcriptional activity by their physical
      protein-protein competition on STAT3.

PMID- 12804610
TI  - Respiratory syncytial virus infection activates STAT signaling in human
      epithelial cells.
AB  - Acute respiratory syncytial virus (RSV) infection causes airway inflammation and
      exacerbates asthma, but the mechanism of inflammation is poorly understood. The
      role of the STAT-signaling pathway in RSV infection in epithelial cells was
      examined in this study. DNA microarray analyses of RSV-infected human alveolar
      type II (A549) epithelial cells identified several genes whose expression was
      altered from -5.5 to +56.4-fold. Four of the highly expressed genes contained
      STAT-binding elements. In A549 and normal human bronchial epithelial cells
      (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1alpha that
      was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor
      or transfection with dominant-negative STAT-1alpha blocked STAT-1alpha activation
      and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked
      this activation. Thus, activation of the STAT-1alpha and STAT-3 pathways play a
      role in RSV infection.

PMID- 12804611
TI  - The meaning of traumatic events as described by nurses in ambulance service.
AB  - Ambulance personnel are working with the injured and dead and are therefore
      exposed to a variety of stressors that can lead to the development of physical,
      psychological and social reactions. Stress among ambulance personnel can be
      regarded as a natural behaviour and reaction when experiencing a traumatic event.
      The aim of this phenomenological study is to uncover the essence of traumatic
      events experienced by Swedish ambulance personnel. Knowledge about such events
      contributes to the awareness of risk for post-traumatic stress symptom and serves
      as a platform for developing measures to handle such stress. In this study,
      written stories from 52 of 223 ambulance nurses and ambulance technicians
      describing an experienced traumatic event, are analysed by the method of van
      Kaam. Findings indicate that the nurses and technicians have a strong
      identification with the victims and it is impossible to prepare for events that
      are unforeseen and meaningless. To handle the overwhelming feelings of
      identification, the personnel have to gain understanding through talking about
      those feelings. Therefore it is important that ambulance management, following
      stressful events, provide the opportunity and time for ambulance personnel to
      share their feelings. Teaching ways of decreasing identification and emotional
      involvement with the victim may also be an effective preventive measure.

PMID- 12804612
TI  - Emergency department mental health triage consultancy service: a qualitative
      evaluation.
AB  - This study evaluated staff perception of a three-month clinical trial of an
      emergency mental health triage and consultancy service. Eleven night duty
      emergency department (ED) staff were interviewed on the last night of the trial.
      Data was analysed according to the standards of qualitative research and through
      content analysis major themes were identified. Staff-perceived value of the
      emergency mental health triage and consultancy service to the emergency
      department was identified under three major themes: "enhancing the quality of
      service for people requiring psychiatric/psychosocial intervention", "the impact
      on the ED environment" and "providing education and support". The findings of
      this study show that ED staff perceived that the emergency mental health triage
      and consultancy service made a valuable contribution to the overall functioning
      of the ED. The findings also highlight the advanced practice role undertaken by
      mental health nurses in the ED.

PMID- 12804613
TI  - Pre-hospital pain management: the paramedics' perspective.
AB  - Current research studies regarding pre-hospital pain management focus on the
      range and efficacy of analgesics available. However, the attitudes and
      perceptions of paramedics towards patients in pain have not been explored. The
      aim of this study therefore, was to explore paramedics' perceptions of patients
      in pain and the paramedics' perspective of pre-hospital pain management. This
      qualitative exploratory study utilised semi-structured interviews to collect in
      depth data from six paramedics working in a UK urban ambulance service. The
      interviews were audio tape-recorded, transcribed and then analysed using a
      thematic content analysis framework. The participants described factors which
      they felt influenced a patient's experience of pain, identifying a cultural
      difference to exist in pain expression. Patients were not always perceived by the
      participants to be honest when describing their pain and this was one of several
      reasons influencing the decision not to administer analgesia. This study has
      revealed small deficits in knowledge, highlighted where additional training would
      be of benefit and established areas to explore through further research.

PMID- 12804614
TI  - Identifying the opportunities for health promoting emergency departments.
AB  - STUDY OBJECTIVE: To describe the opportunities for health promotion in emergency
      departments (EDs). METHODS: A comprehensive literature review and consultation
      with ED staff (seven focus groups) and other health professionals (workshop).
      RESULTS: Opportunities for patient health information and education within EDs
      are described in the literature. In contrast, the health promoting hospitals
      literature showcases integrated approaches for health promotion, emphasizing
      organisational structures, and culture changes to support effective health
      promotion. This type of integration has not developed in EDs, where individual
      issues based health promotion projects have emerged. ED staff readily described
      the:existing health promotion interventions and possible improvements and
      opportunities for potential health promotion interventions related to the needs
      of their patients, the community or their organisation. Other health
      professionals supported EDs taking a greater role in health promotion and
      suggested organisational partnerships that would assist in developing this.
      CONCLUSION: There are numerous opportunities to enhance health promotion in EDs.
      With support, EDs could deliver comprehensive health promotion programs for
      patients, staff, and communities.

PMID- 12804615
TI  - Our patients, our customers: what do they expect from us?

PMID- 12804633
TI  - The distinct gene expression profiles of chronic lymphocytic leukemia and
      multiple myeloma suggest different anti-apoptotic mechanisms but predict only
      some differences in phenotype.
AB  - We compared gene expression in purified tumor cells from untreated patients with
      chronic lymphocytic (CLL) (n=24) and newly diagnosed multiple myeloma (MM) (n=29)
      using the Affymetrix HuGeneFL microarray with probes for approximately 6800
      genes. Hierarchical clustering analysis showed that CLL and MM have distinct
      expression profiles (class prediction). Gene and protein expression (measured by
      flow cytometry) correlated well for CD19, CD20, CD23, and CD138 in CLL and MM,
      but not for immunoglobulin light chain, CD38 and CD79b in CLL, or CD45 and CD52
      in MM. CLL and MM differentially expressed 18% of 130 apoptosis related genes,
      suggesting differences in mechanisms of cell survival.

PMID- 12804634
TI  - Splenic histopathological patterns in chronic myelomonocytic leukemia with
      clinical correlations: reinforcement of the heterogeneity of the syndrome.
AB  - The syndrome of chronic myelomonocytic leukemia (CMML) includes a heterogeneous
      group of patients who exhibit both myelodysplastic and myeloproliferative
      clinicopathological features. Troublesome splenomegaly is uncommon in
      myelodysplastic syndrome (MDS), but when organomegaly occurs, this complication
      is more likely to be associated with myelodysplastic-myeloproliferative overlap
      syndromes such as CMML rather than "dysplasia-only" MDS types such as refractory
      anemia. We report a single-institution experience with splenectomy in CMML
      patients, including a detailed review of splenic histopathology. Twelve patients
      with CMML underwent splenectomy at the Mayo Clinic, primarily because of
      refractory thrombocytopenia and/or mechanical complications related to
      splenomegaly. Three of the 12 patients (25%) died as a direct result of surgery,
      and significant postoperative morbidity was seen in another 4 patients (33%).
      Thrombocytopenia improved in 4 of the 11 patients (36%) with low platelet counts
      before surgery. Three of the four responders had an abundance of CD68 (PGM1)
      positive foamy histiocytes in the marginal zone surrounding the splenic white
      pulp-a pattern which can be seen in immune thrombocytopenia-and two of these
      three patients had thrombocytopenia out of proportion to the degree of anemia pre
      operatively, suggestive of peripheral destruction of platelets. More consistent
      splenic pathological findings in the 12 patients included trilineage
      extramedullary hematopoiesis in splenic red pulp and expansion of splenic cords
      by a myelomonocytic infiltrate. This study underscores both the uniformity and
      diversity of splenic findings in CMML, highlights the potential dangers and
      benefits of splenectomy in this group, and suggests peripheral destruction of
      platelets as a mechanism contributing to thrombocytopenia in a subset of CMML
      patients.

PMID- 12804635
TI  - Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter
      pilot studies in Japan.
AB  - We examined the efficacy of cyclosporin A (CsA) in 50 patients with
      myelodysplastic syndrome (MDS) consisting from 47 of RA, 1 of RARS, and 2 of
      RAEB. These patients showed various marrow cell types including hypo-, normo-,
      and hypercellularity. Patients belonged to the following International Prognostic
      Scoring System (IPSS) risk groups: 4 of low, 41 of intermediate-1, and 5 of
      intermediate-2. The median CsA dose was 4.58mg/kg, and treatment responses were
      classified according to the International Working Group (IWG) criteria.
      Hematological improvement (HI) was observed in 30 (60%) patients, and all of them
      were belonged to RA. In the patients with RARS or RAEB, no efficacy was observed.
      Four (8%) of the responders achieved partial remission (PR) with granulocytes >
      or = 1500microl(-1), Hb>11g/dl and platelets > or = 100,000microl(-1). Higher
      response rate (53%) was shown in erythroid lineage (HI-E) compared to platelet
      (HI-P, 36%) or neutrophil lineage (HI-N, 35%). When we analyzed the correlation
      between the response to CsA therapy and the karyotype or HLA type, there were
      significantly more responders with good karyotype or DRB1*1501 than with
      intermediate/poor karyotypes or with other HLA types. These results indicate the
      usefulness of CsA therapy for MDS patients with any marrow cellularity,
      especially for erythroid lineage and patients with good karyotype or DRB1*1501.

PMID- 12804636
TI  - Direct association of socio-economic status with T-cell acute lymphoblastic
      leukaemia in children.
AB  - Lymphoblasts from 186 consecutive untreated children <18 years were analysed by
      flow cytometry in Brazil. Socio-economic status was defined by family income;
      undernourishment by height and weight for age standardised z scores below -1.28.
      The observed frequencies were precursor-B (pre-B) CD10 positive acute
      lymphoblastic leukaemia (ALL) (CD10+) 65%, pre-B CD10 negative (CD10-) 13%, and T
      ALL 18%. The typical incidence peak at age 2-5 years was observed among the CD10
      positive cases. Nutritional variables were not associated with immunophenotypes.
      Low monthly per capita income was associated with T-immunophenotype (P=0.024). In
      conclusion, a direct association between unfavourable socio-economic status and
      the T-phenotype indicates a potential role of socio-economic factors on the
      genesis of ALL in children, thus confirming indirect data of the international
      literature.

PMID- 12804637
TI  - Dendritic cell vaccination for patients with chronic myelogenous leukemia.
AB  - In this pilot study, we investigated the ability of autologous dendritic cells
      (DCs) pulsed ex vivo with leukemia-specific peptide to stimulate host antitumor
      immunity when administrated as a vaccine. Three patients with chronic myelogenous
      leukemia (CML) received three series of four administration of bcr-abl peptide
      pulsed (1) blood DCs injected intravenously, (2) immature monocyte-derived DCs
      injected intradermally or (3) mature monocyte-derived DCs injected intradermally.
      Vaccination was well tolerated. No major toxicity occurred in any of the
      patients. In method (1), one patient developed peptide-specific cellular immune
      response with no clinical response. In method (2), one patient developed peptide
      specific cellular immune response with no clinical response. In method (3), all
      patients developed peptide-specific cellular immune response with no clinical
      response. The clinical benefits of bcr-abl peptide-specific vaccination in CML
      remain to be determined. Further vaccine development is necessary to increase the
      clinical effect.

PMID- 12804638
TI  - Flow cytometric measurement of phosphorylated STAT5 in AML: lack of specific
      association with FLT3 internal tandem duplications.
AB  - STAT5 phosphorylation has been noted in 69-95% of AML cases by Western blotting.
      We used flow cytometry to measure phosphorylated STAT5 on a semi-quantitative
      scale. The method was validated on K562 cells, which constitutively express
      phosphorylated STAT5, but lose this when BCR-abl tyrosine kinase activity is
      blocked by STI571. Phosphorylated STAT5 was found to measure 2.22+/-0.09 relative
      fluorescence units (RFU) falling to 0.925+/-0.005RFU in the presence of STI571.
      Phosphorylated STAT5 expression was 0.99 to 2.09RFU in 28 primary AML samples.
      There was no logical cut-off point between positive and negative fluorescence.
      FLT3 internal tandem duplications, found in 11/28 samples, were not significantly
      associated with the level of phosphorylated STAT5 expression. We conclude that
      STAT5 phosphorylation can be measured sensitively by flow cytometry in AML and
      that its expression should not be dichotomised as present or absent.

PMID- 12804639
TI  - Loss of imprinting of IGF-II gene in children with acute lymphoblastic leukemia.
AB  - Insulin-like growth factor-II (IGF-II) is known to be involved in the regulation
      of growth, differentiation and cell death in normal human tissues. In a variety
      of human tumors, the IGF-II gene is overexpressed and considered to be a
      stimulator for tumor growth through autocrine and paracrine mechanisms. The IGF
      II gene is normally parental imprinted, only the paternal allele being expressed
      in most tissues. Several reports about biallelic expression (loss of imprinting
      (LOI)) of the IGF-II gene in different tumors suggest a role of dysregulation of
      IGF-II imprinting in tumorigenesis. However, biallelic expression of IGF-II gene
      has also been reported in different tissues of a significant number of normal
      controls, indicating either a normal phenomenon or an elevated cancer risk in
      this group of persons. Although LOI of IGF-II presumably promotes tumorigenesis
      by increasing IGF-II expression, elevated IGF-II levels in those patients have
      not been reported. We studied IGF-II gene expression in malignant lymphoblasts of
      124 children suffering from acute lymphoblastic leukemia, 196 cord blood samples
      from healthy newborns and mononuclear cells (MNC) from 50 healthy age matched
      children. The ApaI polymorphism in exon 9 of the IGF-II gene and allele-specific
      exon-connection RT-PCR was used for determination of the imprinting status. From
      44 informative ALL-patients, 24 (54%) showed LOI of the IGF-II gene. Twenty
      percent of the informative cord blood samples (N=56) and 14% of the informative
      MNC samples from healthy controls (N=22) showed biallelic expression of IGF-II.
      In the ALL-patients, no statistical significant correlation between LOI patients
      and relapse rate, surviving rate and risk groups could be detected. We conclude
      that LOI of IGF-II occurs in malignant lymphoblasts of children suffering from
      acute lymphoblastic leukemia in more than 50% of the patients. In MNC from cord
      blood and peripheral MNC from healthy controls, biallelic expression could be
      detected in up to 20% of all cases. The importance of LOI in ALL-patients needs
      to be further evaluated to determine its impact in leukemogenesis.

PMID- 12804640
TI  - Expression of IL-18 and its receptor in human leukemia cells.
AB  - The importance of IL-18, although clearly established in solid tumors, has not
      been fully elucidated in human hematopoietic neoplasms. Here we examined the mRNA
      and protein for IL-18 in eight human hematopoietic cell lines representing
      different lineages and neoplasms including leukemia, lymphoma and others. Our
      results revealed that IL-18 mRNA was expressed in these cells and that the
      corresponding protein was found in the cytoplasm. Seven of eight cell lines were
      also found to express two subunits of the IL-18 receptor (IL-18R) at varied
      levels. Furthermore, 29 out of 51 leukemia patients tested were observed to
      express IL-18R with 18/29 (62%) co-expression of both receptor and ligand. By
      blocking the IL-18 loop using specific antisense oligodeoxynucleotide (ASON) for
      IL-18 mRNA or anti-human IL-18R monoclonal antibody (McAbR), we were not able to
      demonstrate a marked inhibition on the most leukemic cell lines growth. Moreover,
      the potential proliferation in vitro of primary AML cells co-expressing IL-18 and
      its receptor was not significantly enhanced by recombinant human IL-18,
      suggesting that IL-18 is not apparently implicated in the proliferation of the
      leukemia cells via an autocrine loop. Additionally, we also found the effective
      modulating effect of M-CSF, IFN-alpha and TNF-alpha on IL-18R expression,
      implying an important in vivo effect of cytokines on IL-18-induced reaction.
      Moreover, the modulation of IL-18R expression was possibly irrelevant to IFN
      gamma secretion induced by these cytokines.

PMID- 12804641
TI  - Influence of protein phosphatase inhibitors on HL60 cells death induction by
      dehydrocrotonin.
AB  - Oxidative stress can be involved in several cellular responses, such as
      differentiation, apoptosis and necrosis. Dehydrocrotonin (DCTN, diterpene
      lactone) from Croton cajucara, Brazilian medicinal plant, slightly induced NBT
      reducing activity. In presence of protein phosphatase inhibitors significant
      differentiation of HL60 cells was observed. Flow cytometry analysis demonstrated
      that apoptosis was induced when the cells were treated with okadaic acid (OKA)
      and plus trans-dehydrocrotonin (t-DCTN) this effect was two-fold increased.
      Unlike, when the cells were treated only with t-DCTN, necrosis was observed. On
      the other hand, the necrosis induced by t-DCTN could be due to oxidative stress,
      revealed by increase of GSH content. Therefore, this differentiation pathway
      involves the modulation of protein phosphatases and this inhibition promotes the
      t-DCTN action on apoptosis induction.

PMID- 12804643
TI  - Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance
      to Fas-mediated apoptosis in a subset of familial lymphoma patients.
AB  - Resistance to Fas-mediated apoptosis (FMA) has been implicated in the
      pathogenesis of hematologic malignancies. Recently, a collaborative study showed
      that germline Fas mutations represent a genetic risk factor for the development
      of Hodgkin's and non-Hodgkin lymphoma. Here, we report that transformed B cell
      lines from familial lymphoma patients show a range of sensitivity to Fas-mediated
      apoptosis with lymphocytes from two patients with a marked resistance to Fas-,
      but not p53-mediated cell death. Fas resistance in these cells was associated
      with reduced recruitment of the initiator caspase 8 compared to cFlip, an
      inhibitor of apoptosis, to the death-inducing signaling complex (DISC). A
      decreased ratio of caspase 8 to cFlip in total cell extracts as well as in the
      DISC was associated with a profound disturbance of the Fas signaling cascade. We
      propose here that the relative reduction in caspase 8 to cFlip in the Fas DISC
      confers a survival advantage to lymphocytes and predisposes to the development of
      malignancy in some familial lymphoma patients.

PMID- 12804642
TI  - Aloe-emodin inhibited N-acetylation and DNA adduct of 2-aminofluorene and
      arylamine N-acetyltransferase gene expression in mouse leukemia L 1210 cells.
AB  - N-Acetyltransferases (NATs) plays an important role in the first step of
      arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow
      acetylatoion phenotypes, which are recognized to affect cancer risk related to
      environmental exposure. Aloe-emodin has been shown to exit anticancer activity.
      The purpose of this study is to examine whether or not aloe-emodin could affect
      arylamine N-acetyltransferase (NAT) activity and gene expression (NAT mRNA) and
      DNA-2-aminofluorene (DNA-AF) adduct formation in mouse leukemia cells (L 1210).
      By using high performance liquid chromatography, N-acetylation and non-N
      acetylation of AF were determined and quantitated. By using reverse transcriptase
      polymerase chain reaction (RT-PCR) and PCR, NAT mRNA was determined and
      quantitated. Aloe-emodin displayed a dose-dependent inhibition to cytosolic NAT
      activity and intact mice leukemia cells. Time-course experiments indicated that N
      acetylation of AF measured from intact mice leukemia cells were inhibited by aloe
      emodin for up to 24h. Using standard steady-state kinetic analysis, it was
      demonstrated that aloe-emodin was a possible uncompetitive inhibitor to NAT
      activity in cytosols. The DNA-AF adduct formation in mouse leukemia cells were
      inhibited by aloe-emodin. The NAT1 mRNA in mouse leukemia cells were also
      inhibited by aloe-emodin. This report is the first demonstration which showed
      aloe-emodin affect mice leukemia cells NAT activity, gene expression (NAT1 mRNA)
      and DNA-AF on adduct formation.

PMID- 12804644
TI  - Chronic lymphocytic leukemia (B-CLL) occurring with human immunodeficiency virus
      (HIV) infection: implications.
AB  - Although chronic lymphocytic leukemia (CLL) is the most common leukemia in the
      west and over the past two decades the incidence of infection with the human
      immunodeficiency virus (HIV) has significantly increased, few reports of the
      coincidence of these diseases exist in the literature. Other lymphoid
      malignancies such as non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD)
      occur frequently with HIV and indeed the former is an acquired immune deficiency
      syndrome (AIDS)-defining illness. It is not clear why HIV infected patients have
      a predisposition for some B-cell disorders and not others. This may be related to
      the different age ranges for patients with CLL and HIV infection although an
      overlap clearly does exist. Here, we describe our experience with a patient with
      co-existing HIV infection and CLL and explore possible implications.

PMID- 12804645
TI  - Sustained complete remission of CLL associated with the use of a Chinese herbal
      extract: case report and mechanistic analysis.
AB  - We report the case of a man with chronic lymphocytic leukemia (CLL) who, in the
      absence of cytotoxic chemotherapy, began taking a Chinese herbal extract. Shortly
      thereafter, he experienced a steady decline of his lymphocytosis and adenopathy,
      and he remains in remission now over 10 years later. The herbal extract inhibited
      the survival of primary CLL cells under in vitro culture conditions. However, it
      did not inhibit the activation of Akt or MAP kinase, nor did it inhibit the
      serine phosphorylation of STAT1. Thus, through an as yet unknown mechanism, this
      extract appears to exert pro-apoptotic effects in CLL.

PMID- 12804646
TI  - 2-deoxycoformycin in the treatment of T-large granular lymphocyte leukemia.
AB  - A 52-year-old woman presented to our clinic for investigation of agranulocytosis
      and mild lymphocytosis. A diagnosis of T-large granular lymphocyte leukemia was
      made, based on immunophenotyping findings of the peripheral blood lymphocytes
      (CD3, CD8, CD16, CD57). Flow cytometric analysis of TCR-Vbeta repertoire showed
      single Vbeta9 expression on peripheral T-cells. Clonality was also demonstrated
      with PCR analysis which revealed clonal rearrangement of TCRgamma-chain gene.
      Granulocyte-macrophage colony-stimulating factor (G-CSF) (G-CSF), cyclosporine,
      methylprednisolone and oral methotrexate failed to correct the neutropenia.
      Finally, treatment with 2-deoxycoformycin (DCF) was successful and resulted in
      complete correction of the neutrophil count. Flow cytometric analysis of TCR
      Vbeta repertoire proved to be an effective method to assess the therapeutic
      response to various treatments and to evaluate residual disease.

PMID- 12804647
TI  - Incidence and prognostic significance of C-MPL expression in acute myeloid
      leukemia.

PMID- 12804649
TI  - A toxicologic and dermatologic assessment of linalool and related esters when
      used as fragrance ingredients.

PMID- 12804650
TI  - Fragrance material review on linalool.
AB  - A toxicologic and dermatologic review of linalool when used as a fragrance
      ingredient, is presented.

PMID- 12804651
TI  - Fragrance material review on linalyl acetate.
AB  - A toxicologic and dermatologic review of linalyl acetate when used as a fragrance
      ingredient is presented.

PMID- 12804652
TI  - Fragrance material review on linalyl benzoate.
AB  - A toxicologic and dermatologic review of linalyl benzoate when used as a
      fragrance ingredient is presented.

PMID- 12804653
TI  - Fragrance material review on linalyl butyrate.
AB  - A toxicologic and dermatologic review of linalyl butyrate when used as a
      fragrance ingredient is presented.

PMID- 12804654
TI  - Fragrance material review on linalyl cinnamate.
AB  - A toxicologic and dermatologic review of linalyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 12804655
TI  - Fragrance material review on linalyl formate.
AB  - A toxicologic and dermatologic review of linalyl formate when used a a fragrance
      ingredient is presented.

PMID- 12804656
TI  - Fragrance material review on linalyl hexanoate.
AB  - A toxicologic and dermatologic review of linalyl hexanoate when used as a
      fragrance ingredient is presented.

PMID- 12804657
TI  - Fragrance material review on linalyl isobutyrate.
AB  - A toxicologic and dermatologic review of linalyl isobutyrate when used as a
      fragrance ingredient is presented.

PMID- 12804658
TI  - Fragrance material review on linalyl isovalerate.
AB  - A toxicologic and dermatologic review of linalyl isovalerate when used as a
      fragrance ingredient is presented.

PMID- 12804659
TI  - Fragrance material review on linalyl phenylacetate.
AB  - A toxicologic and dermatologic review of linalyl phenylacetate when used as a
      fragrance ingredient is presented.

PMID- 12804660
TI  - Fragrance material review on linalyl propionate.
AB  - A toxicologic and dermatologic review of linalyl propionate when used as a
      fragrance ingredient is presented.

PMID- 12804661
TI  - Assessment of the acute pulmonary toxicity of lamp oil aspiration in the isolated
      perfused rat lung.
AB  - Mainly among children incidental ingestion of conventional lamp oils (paraffin
      oil) is responsible for casual intoxications with severe pulmonary toxicity and
      fatal consequences. On the basis of the isolated blood-free perfused rat lung we
      developed a model to study the acute toxic effects of lamp oil. Three oils were
      studied: conventional paraffin lamp oil (kinematic viscosity 1.62 10(-6)
      m(2)/sec), the methyl ester Edenor ME C12 70 (2.7 10(-6) m(2)/s) and another
      ester Edenor LPL (4.5 10(-6) m(2)/s). The oils were instilled into the trachea of
      isolated rat lungs and the changes in lung mechanics (tidal volume, pulmonary
      compliance and pulmonary conductance) as well as edema formation (increase in
      lung weight) studied. Instillation of as little as 10 microl paraffin oil caused
      complete failure of lung functions within 20 min and even 2 microl caused
      noticeable edema. Similar results were obtained with Edenor ME C12 70, which
      appeared to be even more toxic than paraffin oil, while Edenor LPL was less
      toxic. We conclude that tracheal instillation of oils into isolated perfused rat
      lungs may be a useful model to study the toxicity of lamp oils in vitro. Our
      findings further suggest that Edenor LPL may be a safer alternative for use as a
      lamp oil than paraffin oil.

PMID- 12804662
TI  - Testicular toxicity of dietarily or parenterally administered bisphenol A in rats
      and mice.
AB  - Male Crj:Wistar rats, HsdHot:Holtzman SD rats, Crj:CD-1(ICR) mice and
      C57BL/6CrSlc mice were administered bisphenol A (BPA) in the diet at a level of 0
      (control) and 0.25% for 8 weeks. Daily BPA intake was about 200 and 400 mg/kg for
      rats and mice, respectively. No conspicuous signs of general or reproductive
      toxicity were observed after administration in any strain of these animals. Serum
      testosterone concentrations were not decreased in BPA-fed rats and mice.
      Successive subcutaneous administration of BPA at a dose of 200 mg/kg/day for 4
      weeks significantly decreased the testis, epididymis, prostate and seminal
      vesicle weights, and the testicular daily sperm production in Jcl:Wistar rats.
      Successive intraperitoneal administration of BPA at a dose of 20 mg/kg/day for 4
      weeks decreased the prostate and seminal vesicle weights but not the testis or
      epididymis weights. An intraperitoneal dose of 2 mg BPA/kg/day did not cause any
      toxicity. These results indicate that dietarily administered BPA is less toxic to
      most strains of rats and mice, and the maximum non-toxic dose and/or minimum
      toxic dose may be about 200 mg/kg/day. Subcutaneous or intraperitoneal BPA is
      much more toxic on male reproductive and sex accessory organs than dietary.

PMID- 12804663
TI  - Inhibition of nicotine-DNA adduct formation in mice by six dietary constituents.
AB  - Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine] is a major alkaloid in tobacco
      products and has proven to be a potential genotoxic compound. Many natural
      dietary products can suppress the DNA adduction, and hence act as inhibitors of
      cancer. In this study, we investigated the inhibitory effects of curcumin, garlic
      squeeze, grapeseed extract, tea polyphenols, vitamin C, and vitamin E on nicotine
      DNA adduction in vivo using an ultrasensitive method of accelerator mass
      spectrometry (AMS). The results demonstrated that all the dietary constituents
      induced marked dose-dependent decrease in nicotine-DNA adducts as compared with
      the control. The reduction rate reached about 50% for all agents, except garlic
      squeeze (40%), even at its highest dose level. Amongst the six agents, grapeseed
      extract exhibited the strongest inhibition to the DNA adduct formation.
      Therefore, we may arrive at a point that these dietary constituents are
      beneficial to prevent the harmful adduct formation, and thus to block the
      potential carcinogenesis induced by nicotine.

PMID- 12804664
TI  - Evoked potentials and transcranial magnetic stimulation in migraine: published
      data and viewpoint on their pathophysiologic significance.
AB  - Migraine is a disorder in which central nervous sytem dysfunction might play a
      pivotal role. Electroneurophysiology seems thus particularly suited to study its
      pathophysiology. We have extensively reviewed evoked potential and transcranial
      magnetic stimulation studies performed in migraineurs in order to identify their
      pathophysiologic significance. Publications available to us were completed by a
      Medline search. Retrieved and personal data were compared with respect to
      methodology and interpreted according to present knowledge on cortical
      information processing. Results are in part contradictory which appears to be
      method-, patient- and disease- related. Nonetheless, both evoked potential and
      transcranial magnetic stimulation studies demonstrate that the cerebral cortex,
      and possibly subcortical structures, are dysfunctioning interictally in both
      migraine with and without aura. These electrophysiologic abnormalities tend to
      normalise just before and during an attack and some of them seem to have a clear
      familial and predisposing character. Besides the studies of magnetophosphenes
      which have yielded contrasting results, chiefly because the method is not
      sufficiently reliable, most recent electrophysiologic investigations of cortical
      activities in migraine favour deficient habituation and decreased preactivation
      cortical excitability as the predominant interictal dysfunctions. We propose that
      the former is a consequence of the latter and that it could favour both
      interictal cognitive disturbances as well as a cerebral metabolic disequilibrium
      that may play a role in migraine pathogenesis. To summarize, electrophysiologic
      studies demonstrate in migraine between attacks a cortical, and possibly
      subcortical, dysfunction of which the hallmark is deficient habituation.

PMID- 12804665
TI  - Functional organization of exteroceptive inhibition following nociceptive
      electrical fingertip stimulation in humans.
AB  - OBJECTIVE: To investigate the functional organization of inhibitory spinal
      reflexes mediated by cutaneous afferents (=cutaneous silent periods, CSPs) in
      order to assess differential strategies used by the human spinal cord to inhibit
      movement in upper limb muscles within the same myotome. METHODS: Twenty healthy
      subjects underwent assessment of the effect of electrical finger-tip stimulation
      with different intensities on voluntarily contracting hand muscles. The rectified
      and averaged electromyogram (EMG) was recorded with surface electrodes placed
      over abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first
      dorsal interosseous (FDI) muscles following recurrent digit II and digit V
      stimulation. RESULTS: Finger-tip stimulation resulted in a series of inhibitory
      and excitatory EMG responses in all 3 hand muscles. Stimulus intensity exerted a
      significant influence on various CSP parameters (probability, onset and end
      latency, duration, index of suppression). CSPs were most pronounced in APB
      following digit II and, somewhat less, following digit V stimulation. FDI and ADM
      differed in CSP onset latency following digit II stimulation, and in the overall
      amount of suppression following digit V stimulation, despite being supplied by
      the same nerve and the same myotome. Excitatory long-loop reflexes seemed to be
      suppressed by increasing stimulus intensities, yet they interfered with CSPs,
      even when using noxious stimulation, in FDI following digit II stimulation, and
      in both ADM and FDI following digit V stimulation. CONCLUSIONS: The findings are
      consistent with the presence of an inhibitory neural circuitry within the human
      spinal cord which can rapidly restrain distinct muscle synergies. Neurophysiology
      indicates a more functional - task-related - organization of protective reflexes
      in the human upper extremity, rather than a merely metameric - anatomically based
      - order of activation of this neuronal circuitry.

PMID- 12804666
TI  - The selective gating of the N30 cortical component of the somatosensory evoked
      potentials of median nerve is different in the mesial and dorsolateral frontal
      cortex: evidence from intracerebral recordings.
AB  - OBJECTIVE: The somatosensory evoked potentials of the median nerve (SEP) were
      registered intracerebrally in 12 subjects to elucidate the origin of N30
      component and its behavior in the motor 'gating' tasks. METHODS: The recordings
      were done from the electrodes which were inserted within the cortex of frontal
      lobe in the pre-surgical phase of epilepsy surgery. The registrations focused on
      the precentral N30 SEP component and its behaviour under the 'gating' paradigms.
      Two different 'gating' paradigms, motor and mental, were used and the SEP then
      were recorded in 3 conditions: (1) normal (N) paradigm, during which the subjects
      were instructed not to perform any movement by the stimulated hand, or to
      mentally simulate the movement; (2) active movement (AM) paradigm, during which
      the subjects were instructed to perform the active movement as the internal motor
      sequence test by the fingers of the hand of the stimulated limb; (3) mental
      movement simulation (MMS), during which the subjects were instructed to only
      mentally simulate the movements performed in the previous paradigm, and this
      'virtual' movement also involved the hand of the stimulated limb. The recordings
      were done at least twice in each paradigm and averaged runs of 2000 artefact-free
      sweeps were used for the analysis. RESULTS: The results demonstrated that the
      precentral N30 component of SEP is generated only in the pre-motor area, either
      dorsolaterally or mesially, which consists of Brodmann's areas 6 and 8, and their
      borders. Only the N30 potentials recorded there in 7 subjects had a shape and
      character of 'near-field' potential. The behaviour of the N30 component when
      recorded in the AM and MMS paradigms was different depending on the fact of
      whether they were recorded dorsolaterally or mesially. When there was a clear
      'near-field' N30 potential recorded mesially, there was a certain gating present
      during the AM paradigm, i.e. during the performance of movement. However, the
      gating caused by the mental movement simulation in the MMS paradigm was
      substantially more expressed, and the N30 wave practically disappeared in some
      cases. On the contrary, the gating of the N30 wave, recorded in the frontal
      dorsolateral premotor cortex (DLPC), was almost complete when the AM (active
      movement) paradigm was employed, and it was only partial when the MMS paradigm
      (mental movement simulation) was employed. CONCLUSIONS: The results of N30
      registrations in our group of patients strongly support the theory of separate
      generator (or generators) of the N30 wave within the premotor cortex. They also
      brought forward evidence that the dorsolateral premotor cortex (Brodmann's areas
      6 and 8) serves as the substrate of the 'motor execution' process, and the mesial
      frontal cortex (Brodmann's area 6) serves as the substrate of the 'motor
      planning' process. Further research should focus on the mutual registration of
      neurophysiological phenomena and imaging phenomena to obtain new data, which will
      be able to more precisely elucidate the workings of the premotor cortex during
      the whole process of motor performance.

PMID- 12804667
TI  - Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in
      patients with multiple sclerosis.
AB  - OBJECTIVE: Somatosensory evoked potentials (SEPs) play a less important role in
      the diagnosis of multiple sclerosis (MS) than visually evoked potentials. Since
      standard SEPs only reflect the dorsal column function, we now investigated
      spinothalamic tract function in patients with MS using laser-evoked potentials
      (LEPs). METHODS: LEPs to thulium laser stimuli (3ms, 540 mJ, 5mm diameter) were
      recorded from 3 midline positions (Fz, Cz, Pz) in 20 patients with MS, and 6
      patients with possible but unconfirmed MS. Peak latencies and peak-to-peak
      amplitude of the vertex potential negativity (N2) and positivity (P2) were
      evaluated and compared with normative values from 22 healthy control subjects.
      Median and tibial nerve SEPs were recorded with standard methods. Depending on
      the results of sensory testing, two skin areas (both hands, both feet, or one
      hand and foot of the same body side) were assessed in each patient. RESULTS: In
      group comparisons, LEPs in patients with MS were significantly delayed and
      reduced in amplitude compared with healthy subjects (P<0.001) or patients with
      suspected but unconfirmed MS (P<0.05). In intraindividual comparisons within the
      patients with MS, LEP amplitude was significantly lower (P<0.01) and latencies
      were significantly longer (N2: P<0.01; P2: P<0.05) for a clinically hypoalgesic
      skin area than an unaffected control area. On a single case basis, LEPs were
      abnormal in 12 (60%) and SEPs in 8 (40%) of the patients with MS; combined
      analysis of LEPs and SEPs raised sensitivity to 75% (15 patients). LEPs were also
      abnormal for 7 skin areas with clinically normal nociception and thermal
      sensitivity, indicating subclinical lesions. Standard SEPs detected subclinical
      lesions in 5 areas with normal tactile sensitivity. CONCLUSIONS: In patients with
      multiple sclerosis, spinothalamic tract function and LEPs were impaired more
      often than dorsal column function and SEPs. LEPs also detected subclinical
      lesions. Combined assessment of LEPs and SEPs can help to document dissemination
      of demyelinating CNS lesions and thus contribute to the diagnosis of multiple
      sclerosis.

PMID- 12804668
TI  - Motor excitability in a patient with a somatosensory cortex lesion.
AB  - OBJECTIVE: We report a patient with an ischemic lesion in right somatosensory
      cortex who developed dystonic posturing and pseudo-athetotic involuntary left
      sided finger movements during voluntary muscle contractions. METHODS: Motor
      excitability was assessed using transcranial magnetic stimulation techniques and
      electrical peripheral nerve stimulation. Results obtained from abductor digiti
      minimi muscles of both hands were compared. RESULTS: On the affected side, silent
      period duration and intracortical inhibition were reduced, indicating a loss of
      inhibitory properties. Intracortical facilitation was enhanced. Stimulus-response
      curves showed a smaller increase of motor evoked potential amplitudes when
      recorded during muscle relaxation, but not during voluntary muscle activation.
      CONCLUSIONS: The results suggest that, under normal conditions, somatosensory
      cortex modifies inhibitory as well as excitatory properties in the motor system.

PMID- 12804669
TI  - Rapid detection of threshold VEPs.
AB  - OBJECTIVE: To determine whether a one-dimensional (1D) Laplacian analysis detects
      steady-state visual evoked potentials (ssVEPs) faster than the standard O(z)-F(z)
      montage and to establish the optimum position of Laplacian reference electrodes.
      METHODS: Twenty-two normal adults were shown reversing checks ranging from 1.5'
      to 60'. Three electrode montages were investigated: O(z)-F(z), LO-F(z) and a 1D
      Laplacian analysis of 3 occipital electrodes (2O(z)-(RO+LO)). RO and LO were
      placed symmetrically and horizontally about O(z). Five different locations for RO
      and LO were investigated. Recordings were analysed in the frequency domain and
      the presence (and detection time, DT) or absence of a ssVEP defined
      statistically. Effects of individual, reference electrode site and check size on
      DT and phase differences between recording montages were investigated. RESULTS:
      Laplacian analysis detected ssVEPs to small (3') checks faster than O(z)-F(z), by
      12.3 and 4.1s on average with Laplacian reference electrodes at 15 and 20% of
      half-head circumference, respectively. The optimum position of reference
      electrodes was governed by the instantaneous spatial spread of the response and
      the noise coherence between midline and lateral electrodes. CONCLUSIONS: A 1D
      Laplacian analysis can reduce the time to statistical detection of ssVEPs
      compared to the traditional O(z)-F(z) recording for stimuli near the normal
      acuity threshold of adults. This in turn could be used to minimise the length of
      a VEP acuity assessment.

PMID- 12804670
TI  - The effects of collinearity and orientation on texture visual evoked potentials.
AB  - OBJECTIVE: The aim of the research was to study the effects of stimulus
      orientation at both the local (textons) and the global (segregated elements)
      level on texture visual evoked potentials (tVEPs). METHODS: Two tVEP paradigms
      were presented to 10 volunteers. The paradigms were characterized by alternating
      uniform textures (random mixture of square dots and lines) and textures in which
      stripes of randomly disposed lines segregated from a square dots' background. In
      one paradigm, the stripes were horizontal and in the other, vertical. The lines
      could be either horizontal or vertical in single stimuli of both paradigms. Thus,
      two stimuli with local/global collinearity and two stimuli without local/global
      collinearity were available. tVEPs were derived from Oz referenced to the left
      earlobe and averaged separately for each condition. Segregation-related
      components were obtained subtracting the traces without segregation from the
      traces with segregation. RESULTS: A negative segregation component starting at
      the latency of P1 and extending until the end of N2 characterized the tVEPs,
      without significant differences among the 4 stimulus conditions. In the presence
      of local/global collinearity, we found an early modulation of N1 amplitude. This
      modulation was orientation-dependent, as vertical collinearity increased N1
      negativity and horizontal collinearity reduced N1 negativity. CONCLUSIONS: Our
      experiment confirms previous findings about the segregation negativity, which may
      depend on contextual modulation of V1 neurons by long-range horizontal and feed
      back connections. The early effect of collinearity may depend on more local
      modulatory connections.

PMID- 12804671
TI  - The assessment of daytime sleep propensity: a comparison between the Epworth
      Sleepiness Scale and a newly developed Resistance to Sleepiness Scale.
AB  - INTRODUCTION: The Epworth sleepiness scale (ESS) is widely used as a way of
      measuring subjective sleep propensity in research and clinical practice.
      Psychometric studies do not rule out the presence of more than one latent
      dimension underlying the items. OBJECTIVE: Aims of the present study were to: (a)
      evaluate psychometric proprieties of the ESS by means of classic psychometric
      techniques; (b) compare them with those from a newly developed resistance to
      sleepiness scale (RSS); (c) evaluate, following the latent trait theory, whether
      the items of both ESS and RSS could be conceptualized as different levels of an
      interval variable representative of a single latent trait related to sleep
      propensity. METHODS: One hundred and forty-six inpatients suffering from
      different sleep disorders filled in both the RSS and ESS in a sleep disorder
      centre. RESULTS: Indexes of fit derived by the application of the extended
      logistic model are consistent with the idea that each ESS item can be
      conceptualized as different levels of an interval variable representative of a
      single latent trait. However, most of the ESS items are found to be located at
      the opposite extremes of this continuum. CONCLUSIONS: The under representation of
      situations characterized by an intermediate soporific nature in the ESS could
      limit ESS sensitivity to detect intermediate variations of sleep propensity.

PMID- 12804672
TI  - A neural complexity measure applied to MEG data in Alzheimer's disease.
AB  - OBJECTIVE: A measure of neural complexity (C(N)) (Proc. Natl Acad. Sci. USA 91
      (1994) 5033) was applied to magnetoencephalography (MEG) data to test the
      hypothesis that C(N) decreases when information processing in the brain is
      impaired, as is the case in patients with Alzheimer's Disease (AD). METHODS: One
      hundred and fifty-one channel MEGs were recorded in 20 AD patients and 20 healthy
      age-matched controls in a resting condition with eyes open (EO) and eyes closed
      (EC). Artifact-free epochs of 117 channels were selected for analysis. C(N) and
      D(2) were computed in different frequency bands, and correlated with the MMSE.
      RESULTS: The Group x Frequency band interaction was significant for both C(N) and
      D(2). C(N) was higher in AD, as compared with controls, in the 2-4 and 4-8Hz
      bands, and D(2) was higher in AD patients in the 14-20 and 20-30Hz bands. The
      C(N) was higher in the EC condition compared to the EO condition, whereas the
      D(2) was higher in the EO condition. CONCLUSIONS: The hypothesis of Tononi et al.
      (Proc. Natl Acad. Sci. USA 91 (1994) 5033) that the neural complexity decreases
      in AD patients has to be rejected. However, both neural complexity and the
      correlation dimension did show differences between controls and AD patients which
      depended on frequency band.

PMID- 12804673
TI  - Movement-activated myoclonus in genetically defined progressive myoclonic
      epilepsies: EEG-EMG relationship estimated using autoregressive models.
AB  - OBJECTIVE: To study electroencephalography-electromyography (EEG-EMG)
      relationships in patients with different forms of progressive myoclonic
      epilepsies (PME). METHODS: EEG-EMG auto-spectra, coherence and phase functions
      were estimated by means of bivariate and time varying autoregressive (AR) models
      in 15 patients: 8 with Unverricht-Lundborg, 4 with Lafora body disease, and 3
      with sialidosis. RESULTS: The coherence spectra of the EMG epochs including
      action myoclonus and contralateral frontocentral EEG derivations showed a main
      beta peak (average coherence: 0.60-0.79) in all patients, regardless of the type
      of PME. The time lag from cortex to muscle was 13.0-21.3 ms. Significantly,
      coherent gamma activity was consistently found only in the 3 patients with
      sialidosis; the most heterogeneous results were obtained in the patients with
      Lafora disease, who showed a more complex coherence profile. Periods of normal
      muscle contractions, which could be recorded in patients with Unverricht-Lundborg
      PME, were characterised by the presence of an EEG-EMG beta coherence peak on the
      same frequency as in the case of action myoclonus, but with a lower coherence
      value. CONCLUSIONS: AR models were capable of describing EEG-EMG relationships in
      patients with PME, and indicated that coherent cortical and EMG beta oscillations
      are crucially involved in the generation of myoclonus. Moreover, they could
      detect the uneven spectral profiles characterising the different forms of PME.

PMID- 12804674
TI  - Spatial spectra of scalp EEG and EMG from awake humans.
AB  - OBJECTIVE: Evaluate spectral scaling properties of scalp electroencephalogram
      (EEG) and electromyogram (EMG), optimal spacing of electrodes, and strategies for
      mitigating EMG. METHODS: EEG was recorded referentially from 9 subjects with a 64
      channel linear array (electrodes 3mm apart) placed parasagittally or transversely
      on forehead or occiput, at rest with eyes open or closed, or with deliberate EMG.
      Temporal (PSD(t)) and spatial (PSD(x)) power spectral densities were calculated
      with one-dimensional fast Fourier transform (FFT) for comparison with earlier
      analyses of intracranial EEG. RESULTS: Scaling of PSD(t) from scalp resembled
      that from pia: near-linear decrease in log power with increasing log frequency
      (1/f(alpha)). Scalp PSD(x) decreased non-linearly and more rapidly than PSD(x)
      from pia. Peaks in PSD(t) (especially 4-12Hz) and PSD(x) (especially 0.1-0.4
      cycles/cm) revealed departures from 1/f(alpha). EMG power in PSD(t) was more
      "white" than 1/f(alpha). CONCLUSIONS: Smearing by dura-skull-scalp distorts
      PSD(x) more than PSD(t) of scalp EEG from 1/f(alpha) scaling at the pia. Spatial
      spectral peaks suggest that optimal scalp electrode spacing might be
      approximately 1cm to capture non-local EEG components having the texture of gyri.
      Mitigation of EMG by filtering is unsatisfactory. A criterion for measuring EMG
      may support biofeedback for training subjects to reduce their EMG. SIGNIFICANCE:
      High-density recording and log-log spectral display of EEG provide a foundation
      for holist studies of global human brain function, as an alternative to network
      approaches that decompose EEG into localized, modular signals for correlation and
      coherence.

PMID- 12804675
TI  - A simulation study of the error in dipole source localization for EEG spikes with
      a realistic head model.
AB  - OBJECTIVE: We tried to determine the error range of dipole modeling for EEG
      spikes originating from various clinically important sources by a simulation
      study employing a realistic head model. The computed error range was also
      compared with the degree of disturbance of dipole modeling caused by adding
      background activity to the spike. METHODS: The scalp fields generated by
      temporal, frontal and rolandic epileptic sources with spatial extent were
      simulated, and the corresponding 3-dimensional maps of residual variance (RV)
      were built by computing the RV for a single dipole at each point on a fine
      imaginary grid in the brain. Single dipole modeling was also performed for the
      simulated scalp fields after adding real background activity. RESULTS: The brain
      volume corresponding to a small RV was compact for the frontal sources and the
      lateral and baso-mesial temporal sources, and large for the anterior and baso
      lateral temporal sources. The distribution of dipoles estimated for spikes
      contaminated with background corresponded to that of the volume of small RV and
      to spike-amplitude. Estimates were improved by employing inferior temporal
      electrodes. CONCLUSIONS: When evaluating dipole models of epileptic spikes, error
      ranges can be estimated and they vary considerably from region to region.
      SIGNIFICANCE: This study illustrates the variability of the error in dipole
      modeling of epileptic spikes. This variability is important when considering the
      clinical interpretation of modeling results.

PMID- 12804676
TI  - Reference values of F wave parameters in healthy subjects.
AB  - OBJECTIVE AND METHODS: A large reference value database for F wave parameters was
      constructed with data from 121 to 196 healthy subjects; the age range of the
      subjects was 14-95 years. We studied the following parameters: minimum F wave
      latency (FMINLAT), mean F wave latency (FMEANLAT), maximum F wave latency
      (FMAXLAT), number of F waves/20 stimuli (FNUMBER) and F wave dispersion
      (FDISP=FMAXLAT-FMINLAT). The median, ulnar, peroneal and tibial nerves were
      studied. RESULTS: Height explains almost half of the FMINLAT variability. The F
      wave latency increases with height in the arms by 0.2 ms/cm and in legs 0.4
      ms/cm. The effect of age on F wave latency in the arms is relatively small, only
      0.03 ms/year; and in the legs age increases the FMINLAT by 0.1 ms/year. Gender
      does not affect FMINLAT in a systematic way. The peroneal nerve has slightly
      longer FMINLAT than the tibial nerve, while the FNUMBER is higher in the tibial
      nerve than the peroneal nerve. The differences between the ulnar and median nerve
      are slight. There is a very high correlation between all 3 latency parameters
      (FMINLAT, FMAXLAT and FMEANLAT), but no correlation between FDISP and FNUMBER and
      the other parameters. Side to side comparisons reveals no significant differences
      in any of the parameters except for the median nerve FMINLAT and FMEANLAT, which
      is 0.2 ms longer on the right than left. If side difference of more than 2
      standard deviation is taken as the upper limit for normal, the side difference in
      arms is 1.4 ms and in legs 3 ms. In repeated studies the interexaminer
      variability is small; the correlation coefficient between the different F
      parameters is high (P>0.6 in arms and P>0.7 in legs). In the arms the upper limit
      for a significant difference of FMINLAT on repeated studies in the median nerve
      is 1.0 and 1.7 ms for the ulnar nerve. In the legs, FMINLAT for the peroneal
      nerve is 2.6 ms and for the tibial nerve is 2.1 ms. CONCLUSIONS: This large
      reference value database can be used not only to evaluate single measurements in
      relation with height and age, but also to compare right and left side and changes
      over time at repeated studies.

PMID- 12804677
TI  - The reason for forearm conduction slowing in carpal tunnel syndrome: an
      electrophysiological follow-up study after surgery.
AB  - BACKGROUND: The exact cause of decreased forearm median motor conduction velocity
      (FMMCV) in carpal tunnel syndrome (CTS) is still a subject of controversy. A
      conduction block or an axonal loss in the large myelinating fibers upon wrist
      compression, or retrograde axonal atrophy, is suspected. METHODS: In order to
      attempt a determination of the cause, 10 patients with clinical symptoms and
      signs of CTS, confirmed using standard electrodiagnosis and with a slowed FMMCV
      <50m/s, were included in this study. Serial standard median motor conduction
      studies were performed at baseline, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12
      weeks after endoscopic ligament release. Serial median motor distal latencies
      (MMDL), compound muscle action potential (CMAP) amplitudes, and FMMCV, were
      determined and compared. RESULTS: Significant improvement in MMDL had occurred at
      the 1-week follow-up examination; however, no such improvement in FMMCV was
      observed. Furthermore, a significant increase in CMAP amplitude was evidenced
      beginning 4 weeks after surgery. The results revealed an improvement in median
      motor conduction, across the wrist segment, that did not parallel the increase in
      FMMCV, suggesting that a conduction block or axonal loss at wrist compression was
      not the likely cause of the decreased FMMCV. CONCLUSIONS: Retrograde axonal
      atrophy, not selective damage to the large myelinating fibers at the wrist, is
      the direct cause of decreased FMMCV in CTS.

PMID- 12804678
TI  - Effects of transcranial magnetic stimulation on the H reflex and F wave in the
      hand muscles.
AB  - OBJECTIVE: In 14 healthy subjects, we studied the effects of transcranial
      magnetic stimulation (TMS) on the excitability of spinal motoneurons in the
      abductor pollicis brevis muscle (ABP), by testing the F wave and H reflex.
      METHODS: TMS pulses were delivered with the subjects at rest and at various motor
      threshold (Mth) intensities. Electrical stimuli were delivered to the median
      nerve at the wrist at two different intensities. High-intensity pulse was used to
      evoke an F wave and low-intensity paired pulse to evoke an H reflex in the ABP
      muscle. The effects of TMS were studied using a conditioning-test paradigm. The
      tests F wave and H reflex were conditioned by TMS (120% Mth) at various
      interstimulus intervals (ISIs) (30-100ms) and intensities (90-200% Mth). RESULTS:
      At 30ms but not at ISIs from 40 to 100ms, conditioning TMS (120% Mth)
      significantly increased the F-wave area. At the 30ms ISI, conditioning TMS at
      120% Mth intensity significantly increased the F-wave area whereas higher
      intensities (140-180% Mth) did not. At 200% Mth intensity, the F-wave area
      decreased significantly. At 30 and 40ms ISIs, conditioning TMS at 120% Mth
      significantly reduced the H-reflex area. At 50-100ms ISIs, the H-reflex area
      almost matched the control value. At the 30ms ISI, conditioning TMS at >or=100%
      Mth intensity significantly decreased the H-reflex area. CONCLUSIONS: In
      conclusion, our findings suggest that the distinct changes in the TMS-conditioned
      F wave and H reflex reflect changing excitability in the motoneuronal populations
      activated by the cortical input.

PMID- 12804679
TI  - Motor-related functional subdivisions of human lateral premotor cortex:
      epicortical recording in conditional visuomotor task.
AB  - OBJECTIVE: To clarify the functional subdivisions of the human lateral premotor
      cortex (PM) in the visuomotor control. METHODS: Event-related potentials (ERPs)
      were epicortically recorded from PM in 5 epilepsy patients. S1-Go/NoGo choice
      delayed reaction time (RT), S1-warned S2-Go simple RT and control fixation
      paradigms were compared using paired visual stimuli (S1, S2). RESULTS: Signal
      related activity peaked at 176-194 ms after S1 in the ventrorostral PM (PMvr) in
      all 3 paradigms, indicating its role in signal perception. Early set-related
      activity was recorded with its peak <810 ms after S1 in the dorsorostral PM
      (PMdr) and was larger in the choice than in the simple RT paradigm, suggesting
      its role in signal selection. Its cognitive component was recorded as surface
      positive transients at PMdr, while its motoric aspect, seen as negative
      transients, extended to the caudal PM. Late sustained set-related activity was
      observed in preparation for hand movement in the caudal PM at the hand and face
      positive motor areas. After presentation of S2, movement-related activity was
      observed at the hand sensorimotor area for motor execution, following the signal
      related activity at PMvr. CONCLUSIONS: The present ERP study suggests the
      temporally sequential representation of predominantly 'cognitive' function in the
      rostral PM and 'motor' function in the caudal PM. SIGNIFICANCE: The rostrocaudal
      cognitive-motor gradient was demonstrated in the lateral premotor cortex in
      humans by means of an epicortical ERP approach.

PMID- 12804680
TI  - Time course of arousal response during periodic leg movements in patients with
      periodic leg movements and restless legs syndrome.
AB  - OBJECTIVE: The temporal evolution of periodic leg movements (PLM) and the
      relationship of their arousing effect on sleep episode has not been extensively
      investigated. We studied the nocturnal evolution of PLM associated or not with
      microarousal (MA) and associated with slow wave activity (PLM with slow wave
      activity) in 23 patients with PLM and/or restless legs syndrome (RLS). METHODS:
      All subjects had PLM associated with MA or with slow wave activity as well as
      without MA and all slept for 4 sleep cycles. Spectral electroencephalogrpahic
      (EEG) analysis was done for the 4 sleep cycles to assess the nocturnal variation
      in slow wave activity (SWA). RESULTS: Sixty percent of PLM were associated with
      MA, 4% were associated with slow wave activity whereas 36% showed no EEG changes.
      There was a clear prevalence of PLM with MA in stages 1 and 2 while PLM without
      MA were prevalent in slow wave sleep. The night-time PLM index progressively
      declined from the first to the last sleep cycle (P<0.005), without differences
      between PLM types, or between PLM and RLS patients. The decline of PLM duplicated
      the temporal trend in SWA over consecutive sleep cycles. CONCLUSIONS: PLM showed
      a typical pattern of progressive decline throughout the night following the
      exponential decline in SWA. These over-time variations occurred independently of
      changes in the rate of PLM associated or not with MA or associated with slow wave
      activity, suggesting that variations in arousal threshold and sleep propensity
      did not affect the PLM arousing effect. The PLM-related arousal response might be
      affected by interaction of circadian and sleep stage influences with the addition
      of sleep oscillatory processes.

PMID- 12804681
TI  - Neurocognitive effects of repetitive transcranial magnetic stimulation in severe
      major depression.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is being
      investigated as a potential treatment for depression. Few studies have addressed
      the neurocognitive effects of a course of rTMS in severely depressed patients. We
      evaluated neurocognitive effects of a 1-4 week course (mean 3 weeks) of rTMS
      using an aggressive set of parameters, in 15 severely depressed subjects.
      METHODS: A battery of neurocognitive tests relevant to attention, working memory
      executive function, objective memory and motor speed were administered to 15
      subjects with treatment-resistant major depression (unipolar and bipolar), before
      and after a course of rTMS. Mean z scores were computed for each of 4 cognitive
      domains and analyzed using repeated measures multivariate analysis of covariance.
      Significant interactions were further clarified using univariate analysis of
      variance. RESULTS: There was no worsening of performance on any of the cognitive
      domains over the baseline-post rTMS period. On the contrary, evidence of modest
      but statistically significant improvement in performance was noted in working
      memory-executive function, objective memory and fine motor speed domains over the
      rTMS treatment period. CONCLUSIONS: There was no evidence of adverse
      neurocognitive changes over the baseline-post rTMS period in 15 treatment
      resistant depressed subjects undergoing a 3 week (mean) trial of rTMS.
      Significant improvements in several domains observed over the rTMS treatment
      period could not be explained by improved mood. Practice effects as well as other
      factors potentially contributing to these findings are discussed. SIGNIFICANCE:
      rTMS is being increasingly studied as a neurophysiological probe as well as for
      its potential antidepressive effects. The effects on neuronal function raise
      appropriate questions of safety of its use at varying stimulus parameters and
      durations. This study contributes to the small body of evidence of the cognitive
      effects of rTMS in severely depressed patients.

PMID- 12804682
TI  - Measuring duration mismatch negativity.
AB  - OBJECTIVE: Automatic comparisons of sound duration in auditory sensory memory are
      typically investigated by comparing event-related potentials (ERPs) to standard
      and deviant stimuli presented in oddball blocks. Deviants elicit mismatch
      negativity (MMN). This procedure might overestimate an MMN contribution
      reflecting automatic sensory memory processes because of differential states of
      refractoriness of respectively recruited neural populations [Neuroreport
      1996;7:3005; Psychophysiology 2001;38:723]. Here, memory-comparison-based
      Duration MMN contributions were investigated using various experimental
      protocols. METHODS: Memory-comparison-based first-order Duration MMN was
      investigated using 4 blocked conditions: (a) descending Deviant (100 ms, P=0.14),
      150 ms Standard; (b) reverse ascending Deviant (150 ms), 100 ms Standard; (c)
      Control comprised of 7 equiprobable durations between 25 and 175 ms; and
      additionally (d) equiprobable tones between 100 and 400 ms. Using the former 3
      conditions, Deviants, Standards and Controls were physically identical. RESULTS:
      Comparing Deviants and Controls excluded potential refractoriness effects, and a
      decomposition of memory-comparison-based MMN and residual MMN was demonstrated.
      Genuine Duration MMN was also obtained in the deviant-standard-reverse
      comparison. CONCLUSIONS: Using a blocked control condition yielded equivalent
      results to reversing the role of deviant and standard in two separate oddball
      blocks. Using the reverse ascending deviant condition is thus sufficient as a
      control.

PMID- 12804683
TI  - Event-related brain potentials in memory: correlates of episodic, semantic and
      implicit memory.
AB  - OBJECTIVE: To study cognitive evoked potentials, recorded from scalp EEG and
      foramen ovale electrodes, during activation of explicit and implicit memory. The
      subgroups of explicit memory, episodic and semantic memory, are looked at
      separately. METHODS: A word-learning task was used, which has been shown to
      activate hippocampus in H(2)(15)O positron emission tomography studies. Subjects
      had to study and remember word pairs using different learning strategies: (i)
      associative word learning (AWL), which activates the episodic memory, (ii) deep
      single word encoding (DSWE), which activates the semantic memory, and (iii)
      shallow single word encoding (SSWE), which activates the implicit memory and
      serves as a baseline. The test included the 'remember/know' paradigm as a
      behavioural learning control. During the task condition, a 10-20 scalp EEG with
      additional electrodes in both temporal lobes regions was recorded from 11 healthy
      volunteers. In one patient with mesiotemporal lobe epilepsy, the EEG was recorded
      from bilateral foramen ovale electrodes directly from mesial temporal lobe
      structures. Event-related potentials (ERPs) were calculated off-line and visual
      and statistical analyses were made. RESULTS: Associative learning strategy
      produced the best memory performance and the best noetic awareness experience,
      whereas shallow single word encoding produced the worst performance and the
      smallest noetic awareness. Deep single word encoding performance was in between.
      ERPs differed according to the test condition, during both encoding and
      retrieval, from both the scalp EEG and the foramen ovale electrode recordings.
      Encoding showed significant differences between the shallow single word encoding
      (SSWE), which is mainly a function of graphical characteristics, and the other
      two strategies, deep single word (DSWE) and associative learning (AWL), in which
      there is a semantic processing of the meaning. ERPs generated by these two
      categories, which are both functions of explicit memory, differed as well,
      indicating the presence or the absence of associative binding. Retrieval showed a
      significant test effect between the word pairs learned by association (AWL) and
      the ones learned by encoding the words in isolation of each other (DSWE and
      SSWE). The comparison of the ERPs generated by autonoetic awareness ('remember')
      and noetic awareness ('know') exhibited a significant test effect as well.
      CONCLUSIONS: The results of behavioural data, in particular that of the
      'remember/know' procedure, are evidence that the task paradigm was efficient in
      activating different kinds of memory. Associative word learning generated a high
      degree of autonoetic awareness, which is a result of the episodic memory, whereas
      both kinds of single word learning generated less. AWL, DSWE and SSWE resulted in
      different electrophysiological correlates, both for encoding as well as
      retrieval, indicating that different brain structures were activated in different
      temporal sequence.

PMID- 12804685
TI  - Exceptional memorizers: made, not born.
AB  - In a recent study, Maguire and colleagues failed to find systematic differences
      in brain anatomy between world-class memory performers and matched control
      subjects. The world-class performers exhibited distinctive patterns of brain
      activation during memorization, but these patterns were directly attributable to
      the experts' unique encoding strategies and acquired memory skills. Discussed
      here are the implications for broad attainability of highly skilled memory
      performance in professional and everyday activities.

PMID- 12804684
TI  - Changes in oscillatory cortical activity related to a visuomotor task in young
      and elderly healthy subjects.
AB  - OBJECTIVE: In order to better understand the spatio-temporal interaction of the
      activated cortical areas when the movement is visuo-guided and to assess the age
      effect on the spatio-temporal pattern of cortical activity, we have compared a
      proximo-distal movement with visual-motor control and hand-eye coordination
      (targeting movement) with a distal and a proximal movement. METHODS: Brain's
      electrical activity was studied using the analysis of event-related
      (de)synchronizations (ERD/S) of cortical mu and beta rhythms in 17 subjects, 8
      young and 9 elderly subjects. RESULTS: In both populations, we found an earlier
      and broader mu and beta ERD during the preparation of the targeting movement
      compared to distal and proximal movements, principally involving the
      contralateral parietal region. During the execution, a spreading over the
      parietocentral region during proximal movement and over the parietal region
      during targeting movement was observed. After the execution of proximal and
      targeting movements, a wider and higher beta ERS was observed only in the young
      subjects. In the elderly subjects, our results showed a significant decrease of
      beta ERS during the targeting task. CONCLUSIONS: These results suggest there was
      a larger recruitment of cortical areas, involving notably the parietal cortex
      when the movement is visuo-guided. Moreover, cerebral aging-related changes in
      the spatio-temporal beta ERS pattern suggests an impaired sensory integration.

PMID- 12804686
TI  - Six-year-olds' contradictory judgments about knowledge and beliefs.
AB  - By around the age of 4 years, children acknowledge that people can have false
      beliefs about the world. Six-year-olds are still inclined, however, to confuse
      their own knowledge with that of more ignorant others. In a recent paper, Hulme,
      Mitchell and Wood offer a novel explanation for six-year-olds' tendency to make
      such errors when asked to choose a picture to put in a story character's thought
      bubble.

PMID- 12804688
TI  - Chimpanzees versus humans: it's not that simple.

PMID- 12804689
TI  - Hemispheric asymmetries of memory: the HERA model revisited.
AB  - The hemispheric encoding/retrieval asymmetry (HERA) model is a process-specific
      description of experimental data provided by a large set of functional
      neuroimaging studies. According to HERA, left prefrontal cortex (PFC) is more
      involved than right PFC in episodic memory encoding, whereas right PFC is more
      involved than left PFC in episodic memory retrieval. Recently it has been claimed
      that this description does not hold for non-verbal materials. Here we propose a
      more precise formulation of HERA than previously, and argue that there is
      sufficient evidence to conclude that HERA, as reformulated, is true for both
      verbal and non-verbal materials.

PMID- 12804690
TI  - The role of similarity in the development of categorization.
AB  - Early in development, humans exhibit the ability to form categories and overlook
      differences for the sake of generality. This ability poses several important
      questions: How does categorization arise? What processes underlie category
      formation? And how are categories mentally represented? We argue that the
      development of categorization is grounded in perceptual and attentional
      mechanisms capable of detecting multiple correspondences or similarities in the
      environment. We present evidence that: (a) similarity can drive categorization
      early in development; and (b) early in development, humans have powerful learning
      mechanisms that enable them to extract regularities in the environment. We
      conclude that, despite remaining challenges, the similarity-based approach offers
      a promising account of the development of categorization.

PMID- 12804691
TI  - What is a visual object?
AB  - The concept of an 'object' plays a central role in cognitive science,
      particularly in vision, reasoning and conceptual development - but it has rarely
      been given a concrete formal definition. Here I argue that visual objects cannot
      be defined according to simple physical properties but can instead be understood
      in terms of the hierarchical organization of visual scene interpretations. Within
      the tree describing such a hierarchical description, certain nodes make natural
      candidates as the 'joints' between objects, representing division points between
      parts of the image that cohere internally but do not perceptually group with one
      another. Thus each subtree hanging from such a node corresponds to a single
      perceived 'object'. This formal definition accords with several intuitions about
      the way objects behave.

PMID- 12804692
TI  - FOXP2 in focus: what can genes tell us about speech and language?
AB  - The human capacity for acquiring speech and language must derive, at least in
      part, from the genome. In 2001, a study described the first case of a gene,
      FOXP2, which is thought to be implicated in our ability to acquire spoken
      language. In the present article, we discuss how this gene was discovered, what
      it might do, how it relates to other genes, and what it could tell us about the
      nature of speech and language development. We explain how FOXP2 could, without
      being specific to the brain or to our own species, still provide an invaluable
      entry-point into understanding the genetic cascades and neural pathways that
      contribute to our capacity for speech and language.

PMID- 12804693
TI  - Emergent constraints on word-learning: a computational perspective.
AB  - In learning the meanings of words, children are guided by a set of constraints
      that give privilege to some potential meanings over others. These word-learning
      constraints are sometimes viewed as part of a specifically linguistic endowment.
      However, several recent computational models suggest concretely how word-learning
      - constraints included - might emerge from more general aspects of cognition,
      such as associative learning, attention and rational inference. This article
      reviews these models, highlighting the link between general cognitive forces and
      the word-learning they subserve. Ultimately, these cognitive forces might leave
      their mark not just on language learning, but also on language itself: in
      constraining the space of possible meanings, they place limits on cross
      linguistic semantic variation.

PMID- 12804694
TI  - Computational models of the hippocampal region: linking incremental learning and
      episodic memory.
AB  - The hippocampal region, a group of brain structures important for learning and
      memory, has been the focus of a large number of computational models. These tend
      to fall into two groups: (1) models of the role of the hippocampal region in
      incremental learning, which focus on the development of new representations that
      are sensitive to stimulus regularities and environmental context; (2) models that
      focus on the role of the hippocampal region in the rapid storage and retrieval of
      episodic memories. Rather than being in conflict, it is becoming apparent that
      both approaches are partially correct and might reflect the different functions
      of substructures of the hippocampal region. Future computational models will help
      to elaborate how these different substructures interact.

PMID- 12804695
TI  - Natural products for cancer prevention: a global perspective.
AB  - The control of cancer, the second leading cause of death worldwide, may benefit
      from the potential that resides in alternative therapies. The primary carcinogens
      stem from a variety of agricultural, industrial, and dietary factors.
      Conventional therapies cause serious side effects and, at best, merely extend the
      patient's lifespan by a few years. There is thus the need to utilise alternative
      concepts or approaches to the prevention of cancer. This review focuses on the
      many natural products that have been implicated in cancer prevention and that
      promote human health without recognisable side effects. These molecules originate
      from vegetables, fruits, plant extracts, and herbs.

PMID- 12804696
TI  - Molecular design and biological activities of protein-tyrosine phosphatase
      inhibitors.
AB  - Protein-tyrosine kinase (PTKase) and protein-tyrosine phosphatase (PTPase)
      regulate the intracellular signal transduction in various biological processes.
      PTPase often negatively regulates the intracellular protein-tyrosine
      phosphorylation. PTPases are considered to be involved in the etiology of
      diabetes mellitus and neural diseases, such as Alzheimer's disease and
      Parkinson's disease. Therefore, PTPase inhibitors should be useful tools to study
      the role of PTPases in these diseases and other biological phenomena, and they
      hopefully may be developed into chemotherapeutic agents. We first discovered a
      naturally occurring PTPase inhibitor, dephostatin, in 1993. Later, we developed
      stable and safe dephostatin analogues by a molecular design approach employing
      the concept of CH/pi interaction. We prepared Et-3,4-dephostatin as a stable
      analogue and found it to inhibit PTP-1B and SHPTP-1 PTPases selectively. Et-3,4
      dephostatin increased the tyrosine phosphorylation of the insulin receptor and
      insulin receptor substrate-1 (IRS-1), with or without insulin, in differentiated
      3T3-L1 mouse adipocytes. It also increased the phosphorylation and activation of
      Akt. The analogue also enhanced translocation of glucose transporter 4 (GLUT4)
      from the cytoplasm to the membrane and 2-deoxyglucose transport. It also showed
      an in vivo antidiabetic effect in terms of reducing the high blood glucose level
      in KK-Ay mice after oral administration. Since Et-3,4-dephostatin contains a
      nitrosamine moiety, we designed nitrosamine-free dephostatin analogues employing
      the concept of CH/pi interaction. Then, we synthesized methoxime- and hexyl
      methoxime-3,4-dephostatin as nitrosamine-free analogues. These analogues also
      showed antidiabetic activity in vivo and illustrate the utility of the CH/pi
      interaction molecular design approach.

PMID- 12804697
TI  - Biochemical and pharmacological control of the multiplicity of coupling at G
      protein-coupled receptors.
AB  - For decades, it has been generally proposed that a given receptor always
      interacts with a particular GTP-binding protein (G-protein) or with multiple G
      proteins within one family. However, for several G-protein-coupled receptors
      (GPCR), it now becomes generally accepted that simultaneous functional coupling
      with distinct unrelated G-proteins can be observed, leading to the activation of
      multiple intracellular effectors with distinct efficacies and/or potencies.
      Multiplicity in G-protein coupling is frequently observed in artificial
      expression systems where high densities of receptors are obtained, raising the
      question of whether such complex signalling reveals artefactual promiscuous
      coupling or is a genuine property of GPCRs. Multiple biochemical and
      pharmacological evidence in favour of an intrinsic property of GPCRs were
      obtained in recent studies. Thus, there are now many examples showing that the
      coupling to multiple signalling pathways is dependent on the agonist used
      (agonist trafficking of receptor signals). In addition, the different couplings
      were demonstrated to involve distinct molecular determinants of the receptor and
      to show distinct desensitisation kinetics. Such multiplicity of signalling at the
      level of G-protein coupling leads to a further complexity in the functional
      response to agonist stimulation of one of the most elaborate cellular
      transmission systems. Indeed, the physiological relevance of such versatility in
      signalling associated with a single receptor requires the existence of critical
      mechanisms of dynamic regulation of the expression, the compartmentalisation, and
      the activity of the signalling partners. This review aims at summarising the
      different studies that support the concept of multiplicity of G-protein coupling.
      The physiological and pharmacological relevance of this coupling promiscuity will
      be discussed.

PMID- 12804698
TI  - Effects of amphetamines on mitochondrial function: role of free radicals and
      oxidative stress.
AB  - Amphetamine-like psychostimulants are associated with long-term decreases in
      markers for monoaminergic neurons, suggesting neuronal loss and/or damage within
      the brain. This long-term "toxicity" results from formation of free radicals,
      particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS),
      although the mechanism(s) of ROS and RNS formation are unclear. Mitochondria are
      a major source of ROS and mitochondrial dysfunction has been linked to some
      neurodegenerative disorders. Amphetamines also inhibit mitochondrial function,
      although the mechanism involved in the inhibition is uncertain. This review
      coordinates findings on the multiple pathways for ROS and RNS and describes a
      hypothesis involving mitochondrial inhibition in the initiation of amphetamine
      induced cellular necrosis.

PMID- 12804699
TI  - Antisense therapeutics: from theory to clinical practice.
AB  - The use of antisense (AS) oligonucleotides as therapeutic agents was proposed as
      far back as the 1960s/1970s when the AS strategy was initially developed.
      However, it has taken almost a quarter of a century for this potential to be
      realized. The last few years has seen a rapid increase in the number of AS
      molecules progressing past Phase I in clinical trials, due in part to our
      increased knowledge of their structure and chemistry. Here, we describe the most
      prominent of these modifications with respect to clinical applicability. However,
      the main focus of this review is clinical application, with a focus on cancer. We
      will discuss in detail both the status of the current AS clinical trials and the
      molecules that are likely to be the targets of the next group of AS molecules
      entering the clinic.

PMID- 12804700
TI  - N-methyl-D-aspartate glutamate receptors and alcoholism: reward, dependence,
      treatment, and vulnerability.
AB  - This review takes a translational neuroscience perspective on the role of
      glutamate systems in human ethanol abuse and dependence. Ethanol is a simple
      molecule with profound effects on many chemical systems in the brain. Glutamate
      is the primary excitatory neurotransmitter in the brain. Glutamatergic systems
      are targets for the actions of ethanol via its antagonism of the N-methyl-D
      aspartate (NMDA) subtype of the glutamate receptor and other mechanisms. The
      modulation of glutamatergic function by ethanol contributes to both euphoric and
      dysphoric consequences of ethanol intoxication. Adaptations within glutamatergic
      systems appear to contribute to ethanol tolerance and dependence and to both
      acute and protracted features of ethanol withdrawal. Perhaps because of the
      important glutamatergic mediation of the behavioral effects of ethanol,
      glutamatergic systems appear to contribute to the vulnerability to alcoholism,
      and novel glutamatergic agents may play a role in the treatment of ethanol abuse
      and dependence.

PMID- 12804701
TI  - The lipid and non-lipid effects of statins.
AB  - The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, more
      commonly known as statins, are a class of drug widely used for the treatment of
      hypercholesterolaemia in patients with established cardiovascular disease as well
      as those at high risk of developing atherosclerosis. Their predominant action is
      to reduce circulating levels of low-density lipoprotein (LDL) cholesterol; to a
      smaller degree, they also increase high-density lipoprotein (HDL) cholesterol and
      reduce triglyceride concentrations. In recent years, however, there has been an
      increasing body of evidence that their effects on lipid profile cannot fully
      account for their cardiovascular protective actions: their beneficial effects are
      too rapid to be easily explained by their relatively slow effects on
      atherogenesis and too large to be accounted for by their relatively small effects
      on plaque regression. Experimental models have revealed that statins exert a
      variety of other cardiovascular effects, which would be predicted to be of
      clinical benefit: they possess anti-inflammatory properties, as evidenced by
      their ability to reduce the accumulation of inflammatory cells in atherosclerotic
      plaques; they inhibit vascular smooth muscle cell proliferation, a key event in
      atherogenesis; they inhibit platelet function, thereby limiting both
      atherosclerosis and superadded thrombosis; and they improve vascular endothelial
      function, largely through augmentation of nitric oxide (NO) generation. The
      relative importance of the lipid- and non-lipid-related effects of the statins in
      the clinical situation remains the subject of much continuing research.

PMID- 12804702
TI  - Immune responses in cancer.
AB  - The complex of humoral factors and immune cells comprises two interleaved
      systems, innate and acquired. Immune cells scan the occurrence of any molecule
      that it considers to be nonself. Transformed cells acquire antigenicity that is
      recognized as nonself. A specific immune response is generated that results in
      the proliferation of antigen-specific lymphocytes. Immunity is acquired when
      antibodies and T-cell receptors are expressed and up-regulated through the
      formation and release of lymphokines, chemokines, and cytokines. Both innate and
      acquired immune systems interact to initiate antigenic responses against
      carcinomas. A new approach to the treatment of cancer has been immunotherapy,
      which aims to up-regulate the immune system in order that it may better control
      carcinogenesis. Currently, several forms of immunotherapy that use natural
      biological substances to activate the immune system are being explored
      therapeutically. The various forms of immunotherapy fall into three main
      categories: monoclonal antibodies, immune response modifiers, and vaccines. While
      these modalities have individually shown some promise, it is likely that the best
      strategy to combat cancer may require multiple immunotherapeutic strategies in
      order to demonstrate benefit in different patient populations. It may be that the
      best results are obtained with vaccines in combination with a variety of
      immunotherapy combinations. Another potent strategy may be in combining with more
      traditional cancer drugs as evidenced from the benefit derived from enhancing the
      efficacy of chemotherapy with cytokines. Through such concerted efforts, a
      durable, therapeutic antitumour immune response may be achieved and maintained
      over the course of a patient's lifespan.

PMID- 12804703
TI  - Entrance dose measurement: a simple and reliable technique.
AB  - Verification of tumor dose for patients undergoing external beam radiotherapy is
      an important part of quality assurance programs in radiation oncology. Among the
      various methods available, entrance dose in vivo is one reliable method used to
      verify the tumor dose delivered to a patient. In this work, entrance dose
      measurements using LiF:Mg;Ti and LiF:Mg;Cu;P thermoluminescent dosimeters (TLDs)
      without buildup cap was carried out. The TLDs were calibrated at the surface of a
      water equivalent phantom against the maximum dose, using 6- and 10-MV photon and
      9-MeV electron beams. The calibration geometry was such that the TLDs were placed
      on the surface of the "solid-water" phantom and a calibrated ionization chamber
      was positioned inside the phantom at calibration depth. The calibrated TLDs were
      then utilized to measure the entrance dose during the treatment of actual
      patients. Measurements were also carried out in the same phantom simultaneously
      to check the stability of the system. The dose measured in the phantom using the
      TLDs calibrated for entrance dose to 6-and 10-MV photon beams was found to be
      close to the dose determined by the treatment planning system (TPS) with
      discrepancies of not more than 4.1% (mean 1.3%). Consequently, the measured
      entrance dose during dose delivery to the actual patients with a prescribed
      geometry was found to be compatible with a maximum discrepancy of 5.7% (mean
      2.2%) when comparison was made with the dose determined by the TPS. Likewise, the
      measured entrance dose for electron beams in the phantom and in actual patients
      using the calibrated TLDs were also found to be close, with maximum discrepancies
      of 3.2% (mean 2.0%) and 4.8% (mean 2.3%), respectively. Careful implementation of
      this technique provides vital information with an ability to confidently accept
      treatment algorithms derived by the TPS or to re-evaluate the parameters when
      necessary.

PMID- 12804704
TI  - Independent calculations to validate monitor units from ADAC treatment planning
      system.
AB  - Current standards of practice are based on the use of an independent calculation
      to validate the monitor units (MUs) derived from a treatment planning system. The
      ADAC PINNACLE treatment planning system has shown discrepancies of 10% or more
      compared to simple independent calculations for highly contoured areas such as
      tangential breast and chest wall irradiation. The ADAC treatment planning system
      generally requires more MUs to deliver the same prescribed dose. Independent MU
      calculation methods are based on full phantom conditions. On the other hand, the
      MUs from the ADAC treatment planning system are derived using realistic phantom
      scatter. As such, differences exist in TMR factors, off-axis wedge factors, and
      the phantom scatter factor. To systematically study the discrepancies due to
      phantom conditions, experimental measurements were performed with various
      percentages of tissue missing. The agreement between the experimental
      measurements and ADAC calculations was found to be within 2%. Using breast field
      geometry, a relationship between missing tissue and the dosimetric parameters
      used by ADAC was developed. This relationship, when applied, yielded independent
      MU calculations whose values closely matched those from the ADAC treatment
      planning system.

PMID- 12804705
TI  - Study on dosimetric parameters for stereotactic radiosurgery and intensity
      modulated radiotherapy.
AB  - This study is an attempt to compare the dosimetric parameters of intensity
      modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS) using
      patient data. Radiosurgery was delivered through circular tertiary collimators
      attached to a linear accelerator. Six patients who were treated with SRS were
      replanned and evaluated with the IMRT planning system. Contouring of all
      structures, including target volume, was done on the IMRT system to closely match
      the SRS system. Treatment plans were generated after specifying the goals in the
      prescription module. The NOMOS BEAK collimator attached to the NOMOS MIMiC
      delivery device was chosen for treatment delivery. Various parameters such as
      conformity index, homogeneity index, target volume coverage, nontarget tissue,
      and brainstem doses were calculated and compared between the IMRT and SRS
      systems. Patient data were divided into 2 groups based on the complexity of the
      lesion and the number of isocenters used for radiosurgery. Analysis was done for
      each group and for the cumulative data. Superior conformality and homogeneous
      dose distribution in IMRT for multiple isocenter cases were observed. In
      addition, critical structure volumes for 50%, 70%, and 90% of the prescribed dose
      were lower in IMRT compared to SRS treatment. However, nontarget tissue received
      significantly higher doses with IMRT plans. Results show that IMRT treatment
      modality produces similar results as radiosurgery for small, spherical lesions,
      whereas it is found to be superior to SRS for irregular lesions in terms of
      critical structure sparing and better dose homogeneity.

PMID- 12804706
TI  - Visual verification of linac light and radiation fields coincidence.
AB  - X-ray and light field alignment evaluation is carried out during linac quality
      assurance programs. In this paper, we compare the size of the light field
      measured by a photodiode and by a more traditional visual observation with the
      size of the x-ray field. The comparison between actual light field size, measured
      with the photodiode, and light field size measured by human eye allow us to
      verify the reliability of human eye in the evaluation of this parameter. The
      visual field is always larger than real light field; however, it agrees better
      with the x-ray field. It matches the light field if we take into account the 25%
      (+/- 1%) of the decrement line of the maximum central lightening; however, this
      method simulates better the actual field employed in radiation treatments.

PMID- 12804707
TI  - Orbital lymphoma: a simple treatment using electrons.
AB  - Previous papers have discussed the successful treatment of orbital lymphoid
      tumors using a low-vacuum contact lens placed directly on the eye and the use of
      a lead bar suspended over the eye with a retort stand. In this paper, a novel
      approach using a cerrobend bar attached to an electron shield for the treatment
      of a conjunctival lymphoma is presented. With this approach, the entire eye,
      excluding the lens, may be treated with a single field. Isodose distributions
      measured in a water phantom are compared with those planned on a 3D radiotherapy
      treatment planning system, where the effects of an external eye bar can be shown.
      The clinical outcome of the treatment is also shown.

PMID- 12804708
TI  - Electron dose calculations: a comparison of two commercial treatment planning
      computers.
AB  - The accuracy of electron dose calculations performed by two commercially
      available treatment planning systems, Varian Cadplan and MDS Nordion Helax-TMS,
      were assessed. Three tests designed to reproduce clinical treatments likely to
      result in dose nonuniformity have been carried out. The tests examined oblique
      incidence of the electron beam; incidence on a surface containing a step shape;
      and incidence on a phantom containing a small air cavity. Dose calculations
      performed by the planning systems were compared with thermoluminescence dosimetry
      (TLD) measurements in a WTe electron solid water phantom. A Varian 2100C linear
      accelerator was used. In most situations, the discrepancy between calculated and
      measured dose was within the tolerance specified by the ICRU; however, some
      exceptions were noted. Helax-TMS produced errors of 5 mm in the position of the
      10% isodose line in the penumbra of the obliquely incident beam. Both Cadplan and
      Helax-TMS overestimated the surface dose adjacent to a step in the beam entry
      surface by approximately 15%. An overestimation of 10% in dose was calculated by
      both systems downstream of the small air cavity. Discrepancies between the
      measured and calculated monitor units lay within the uncertainty limits of the
      measurements. In conclusion, calculations of absorbed dose from electron beams
      performed by Varian Cadplan and MDS Nordion Helax-TMS result in significant
      errors at shallow depths near surface irregularities and downstream of small air
      cavities.

PMID- 12804709
TI  - Radiotherapy dose calculations in the presence of hip prostheses.
AB  - The high density and atomic number of hip prostheses for patients undergoing
      pelvic radiotherapy challenge our ability to accurately calculate dose. A new
      clinical dose calculation algorithm, Monte Carlo, will allow accurate calculation
      of the radiation transport both within and beyond hip prostheses. The aim of this
      research was to investigate, for both phantom and patient geometries, the
      capability of various dose calculation algorithms to yield accurate treatment
      plans. Dose distributions in phantom and patient geometries with high atomic
      number prostheses were calculated using Monte Carlo, superposition, pencil beam,
      and no-heterogeneity correction algorithms. The phantom dose distributions were
      analyzed by depth dose and dose profile curves. The patient dose distributions
      were analyzed by isodose curves, dose-volume histograms (DVHs) and tumor control
      probability/normal tissue complication probability (TCP/NTCP) calculations. Monte
      Carlo calculations predicted the dose enhancement and reduction at the proximal
      and distal prosthesis interfaces respectively, whereas superposition and pencil
      beam calculations did not. However, further from the prosthesis, the differences
      between the dose calculation algorithms diminished. Treatment plans calculated
      with superposition showed similar isodose curves, DVHs, and TCP/NTCP as the Monte
      Carlo plans, except in the bladder, where Monte Carlo predicted a slightly lower
      dose. Treatment plans calculated with either the pencil beam method or with no
      heterogeneity correction differed significantly from the Monte Carlo plans.

PMID- 12804710
TI  - Image reconstruction and the effect on dose calculation for hip prostheses.
AB  - High atomic number inserts, such as hip prostheses and dental fillings, cause
      streak artifacts on computed tomography (CT) images when filtered back-projection
      (FBP) methods are used. These streak artifacts severely degrade our ability to
      differentiate the tumor volume. Also, incorrect Hounsfield numbers yield
      incorrect electron density information that may lead to erroneous dose
      calculations, and, as a result, compromise clinical outcomes. The aim of this
      research was to evaluate the dosimetric consequences of artifacts during
      radiotherapy planning of a prostate patient containing a hip prosthesis. The CT
      numbers corresponding to an iron prosthesis were inserted into the right femoral
      head of an existing CT image set. This artifact-free image was used as the
      standard image set. CT projections through the image set formed the sinogram,
      from which filtered back projection and iterative deblurring methods were used to
      create reconstructed image sets. These reconstructed image sets contained
      artifacts. Prostate treatment plans were then calculated using a Monte Carlo
      system for the standard and reconstructed CT image sets. Close to the prosthesis,
      the CT numbers between the reconstructed and standard image sets differed
      substantially. However, because the CT number differences covered only a small
      area, the dose distributions on the reconstructed and standard image sets were
      not significantly different. The dose-volume histograms for the prostate, rectum,
      and bladder were virtually identical. Our results indicate that even though CT
      image artifacts restrict our ability to differentiate tumors and critical
      structures, the dose distributions for a prostate plan containing a hip
      prosthesis, calculated on both artifact-free image sets and image sets containing
      artifacts, are not significantly different.

PMID- 12804711
TI  - A semiempirical method for the description of off-center ratios at depth from
      linear accelerators.
AB  - A semiempirical method for the description of the off-center ratios (OCR) at
      depth from linear accelerators is presented, which is based on a method
      originally developed for cobalt-60 (60)Co units. The OCR profile is obtained as
      the sum of 2 components: the first describes an OCR similar to that from a (60)Co
      unit, which approximates that resulting from the modification of the original x
      ray intensity distribution by the flattening filter; the second takes into
      account the variable effect of the flattening filter on dose profile for
      different depths and field sizes, by considering the existence of a block and
      employing the negative field concept. The above method is formulated in a
      mathematical expression, where the parameters involved are obtained by fitting to
      the measured OCRs. Using this method, OCRs for various depths and field sizes,
      from a Philips SL-20 for the 6 MV x-ray beam and a Siemens Primus 23, for both
      the 6-MV and 23-MV x-ray beams, were reproduced with good accuracy. Furthermore,
      OCRs for other fields and depths that were not included in the fitting procedure
      were calculated using linear interpolation to estimate the values of the
      parameters. The results indicate that this method can be used to calculate OCR
      profiles for a wide range of depths and field sizes from a measured set of data
      and may be used for monitor unit calculations for off-axis points using a
      standard geometry. It may also be useful as a quality control tool to verify the
      accuracy of lacking profiles calculated by a treatment planning system.

PMID- 12804712
TI  - Verification techniques and dose distribution for computed tomographic planned
      supine craniospinal radiation therapy.
AB  - A modified 3-field technique was designed with opposed cranial fields and a
      single spinal field encompassing the entire spinal axis. Two methods of plan
      verifications were performed before the first treatment. First, a system of
      orthogonal rulers plus the thermoplastic head holder was used to visualize the
      light fields at the craniospinal junction. Second, film phantom measurements were
      taken to visualize the gap between the fields at the level of the spinal cord.
      Treatment verification entailed use of a posterior-anterior (PA) portal film and
      placement of radiopaque wire on the inferior border of the cranial field. More
      rigorous verification required a custom-fabricated orthogonal film holder. The
      isocenter positions of both fields when they matched were recorded using a record
      and-verify system. A single extended distance spinal field collimated at 42
      degrees encompassed the entire spinal neuraxis. Data were collected from 40
      fractions of craniospinal irradiation (CSI). The systematic error observed for
      the actual daily treatments was -0.5 mm (underlap), while the stochastic error
      was represented by a standard deviation of 5.39 mm. Measured data across the
      gapped craniospinal junction with junction shifts included revealed a dose
      ranging from 89.3% to 108%. CSI can be performed without direct visualization of
      the craniospinal junction by using the verification methods described. While the
      use of rigorous film verification for supine technique may have reduced the
      systematic error, the inability to visualize the supine craniospinal junction on
      skin appears to have increased the stochastic error compared to published data on
      such errors associated with prone craniospinal irradiation.

PMID- 12804713
TI  - Is cell surface calreticulin involved in phagocytosis by insect hemocytes?
AB  - The innate immune system of insects consists of humoral and cellular components
      involved in the recognition of and responses to intruding foreign micro- or
      macroorganisms. Several molecules have been identified so far that recognize
      molecular patterns present on microorganisms, such as lipopolysaccharides,
      peptidoglycans and lipoteichonic acid. These molecules, acting as opsonins,
      trigger immune responses such as phagocytosis, nodule formation, melanization and
      encapsulation. Here, we investigated the role of calreticulin (CRT) present on
      the surface of Pieris rapae hemocytes in phagocytosis. Comparative phagocytosis
      assays using yeast cells showed that hemocytes from different insects exhibit
      significant variation in their phagocytosing potential and relative CRT
      involvement.

PMID- 12804714
TI  - Hormonal regulation of the expression of two storage proteins in the larval fat
      body of the greater wax moth (Galleria mellonella).
AB  - During larval development of the greater wax moth, Galleria mellonella, genes of
      storage proteins LHP76 and LHP82 are tissue- and stage-specifically expressed. In
      this study, hormonal regulation of this expression has been investigated in vivo.
      Messenger RNAs of the juvenile hormone (JH-suppressible) Lhp82 gene are present
      only during the feeding period of the final larval instar, suggesting that a high
      level of JH during earlier stages prevents its expression and that a small rise
      in JH titer observed on day 8 of the final larval instar is responsible for the
      rapid shut-off of its transcription. Application of 1micro g of JH analog
      (fenoxycarb) specifically inhibits expression of Lhp82, whereas Lhp76 mRNAs
      remain at the same level. 20-hydroxyecdysone (20HE) does not exert any inhibitory
      effects on transcription of Lhp genes when injected in a dose of 0.5 or 1.5 micro
      g per individual, regardless of larval age. However, the same dose of 20HE
      significantly lowers the rate of LHPs synthesis within the fat body and
      completely blocks secretion of LHPs into the hemolymph. Therefore, we propose
      that 20HE inhibits the synthesis of storage proteins and their secretion without
      altering the level of mRNAs.

PMID- 12804715
TI  - Regulation of sexual receptivity of female Mediterranean fruit flies: old
      hypotheses revisited and a new synthesis proposed.
AB  - The objective of this study was to examine the relative contributions of copula
      duration and sperm transfer to the inhibition of sexual receptivity of female
      Mediterranean fruit flies (Ceratitis capitata, Diptera: Tephritidae). Females
      choosing to remate had significantly fewer sperm in their spermathecae than
      females who chose not to remate. Duration of a female's first copulation did not
      affect her subsequent receptivity. Furthermore, on the first day following
      copulation significantly more females whose first mate was sterile and from a
      laboratory strain (sterile males transfer fewer sperm than wild males) chose to
      copulate than did females whose mate was fertile and recently derived from wild
      stock. Finally, we offer a synthesis of the available information on remating in
      this species, and suggest that while females are facultatively polyandrous,
      copula duration, sperm transfer and male accessory gland secretions act in
      succession to inhibit female receptivity.

PMID- 12804716
TI  - Inhibition of pheromone biosynthesis in Helicoverpa armigera by pheromonostatic
      peptides.
AB  - Male insect accessory glands contain factors that are transferred during mating
      to the female, some inducing post-mating behavior, including the cessation of
      pheromone production, non-receptivity and the initiation of oviposition. One such
      factor is the Drosophila melanogaster sex-peptide (DrmSP). A pheromone
      suppression peptide, termed HezPSP, was identified in the moth Helicoverpa zea,
      isolated by HPLC and the active peak sequenced, but the activity of the
      synthesized peptide has not been reported to date. HezPSP bears no sequence
      homology to DrmSP. However, both peptides contain a disulfide bridge separated by
      an equal number, but dissimilar, amino acids. We herein report on the
      pheromonostatic activity of HezPSP partial peptides in the moth Helicoverpa
      armigera.

PMID- 12804717
TI  - Life history of flight morph females of Callosobruchus maculatus F.: evidence of
      a reproductive diapause.
AB  - Callosobruchus maculatus (F.) (Coleoptera : Bruchidae) is a tropical beetle that
      develops in the seeds of Vigna unguiculata. C. maculatus adults show an imaginal
      polymorphism with differences in morphological, behavioral and reproductive
      characteristics. Adults of the flight morph that emerge in cowpea storage systems
      were studied under natural climatic conditions. A large number of the flight
      morph females were in reproductive diapause and had a long imaginal life. These
      females did not synthesize vitellogenin, produced a specific diapause protein and
      possessed significant protein reserves. This suggests that the beetles survived
      in the tropical ecosystem for a long time and colonized the crops during the
      cowpea growing and flowering phases. Analysis of reproductive activity in females
      captured in the V. unguiculata crops indicates that they terminated their
      reproductive diapause and began to lay eggs as soon as the pods were formed. Few
      females of the flight morph were sexually active at the beginning of imaginal
      life. In this paper we discuss the adaptive significance of these two
      reproductive strategies in females of C. maculatus.

PMID- 12804718
TI  - Juvenile hormone titre and egg production in Tenebrio molitor infected by
      Hymenolepis diminuta: effect of male and/or female infection, male age and
      mating.
AB  - Infection of Tenebrio molitor with Hymenolepis diminuta induces curtailment of
      female fertility. We examined ovulation and oviposition, and associated titres of
      juvenile hormone (JH), in relation to parasitism and mating. Oviposition was
      significantly increased in infected mated and virgin beetles by days 6 and 9 post
      emergence. Ovulation was not changed by infection; by the end of the 18-day
      experiment, the total number of laid eggs was not significantly altered. On day
      6, JH levels were significantly higher in virgin infected insects, compared to
      non-infected controls (236+/-37.7 and 107+/-9.62 pg/g wet weight). Oviposition
      increased after mating, but total eggs ovulated remained the same. JH levels were
      higher in mated females on days 12 and 18 post-emergence, for infected and
      control insects. Previous studies suggested that male reproductive potential
      might rise following infection, because uninfected females lay more eggs when
      mated to infected males. We tested whether this caused an increase in female JH.
      Males were mated on days 5 or 12, when significant changes in their reproductive
      physiology begin to be observed, and are maximal, respectively. However, male age
      was of greater significance in promoting JH levels in females (p=0.001), than
      infection status of either partner (p=0.33).

PMID- 12804719
TI  - Proline can be utilized as an energy substrate during flight of Aedes aegypti
      females.
AB  - In order to determine whether proline can be utilized as fuel during flight of
      Aedes aegypti, proline, alanine, and glutamine concentrations were monitored at
      0, 30 and 60 min after flight using sugar-fed males and females, and blood meal
      fed females. In sugar-fed and blood meal-fed females, flight lead to a
      significant decrease in proline and a significant increase in glutamine
      concentration in both hemolymph and thorax. Only during flight after a blood meal
      was a significant increase in the alanine concentration observed in hemolymph.
      After flight, the proline alanine and glutamine levels in the hemolymph and
      thorax from males did not change significantly. In addition, activities of
      enzymes related to amino acid metabolism were assayed in homogenates of
      cephalothorax and thorax from both sexes, and in fat body and midgut from
      females. In both sexes, the activities of all the enzymes studied were
      significantly higher in thorax than in cephalothorax. The levels of the enzymes
      involved in proline oxidation were higher in thorax than in fat body and midgut.
      These results suggest that proline can be used as an energy substrate for flight
      muscle of Ae. aegypti females. However, the elevation in glutamine levels
      observed in hemolymph and thorax after flight has not been reported in other
      insects that fuel flight using proline and may suggest an additional mechanism
      for shuttling ammonia between flight muscle and fat body is present in
      mosquitoes.

PMID- 12804720
TI  - Biosynthetic maturation of the corpus allatum of the female adult medfly,
      Ceratitis capitata, and its putative control.
AB  - The major juvenile hormone (JH) homolog synthesized in vitro by the adult female
      Medfly (Ceratitis capitata) corpus allatum (CA) is JHB(3), with JH-III the minor
      homolog. Methyl-incorporation in vitro in post-eclosion virgin females is age
      dependent. Basal activity occurs during the first four days post-eclosion and
      increases significantly thereafter, peaking at five days. Biosynthetic maturation
      of the mated female CA is delayed by one day and reduced considerably. The
      delayed response may be due to direct cerebral or neural inhibition. Synthetic
      Drosophila melanogaster sex peptide depresses JH biosynthesis by the Medfly
      female CA in vitro. Male-derived accessory gland peptides of the Medfly are
      transferred to the female during mating and a Medfly SP-analog may be responsible
      for down-regulation of JH synthesis by the CA in mated Medfly females. Mevinolin,
      an inhibitor of the mevalonate pathway, significantly reduces the biosynthesis of
      JHB(3), while farnesoic acid, a proximate precursor of JHIII, significantly
      stimulates the biosynthesis of both JHB(3) and JHIII in vitro.

PMID- 12804721
TI  - Tarsal movements in flies during leg attachment and detachment on a smooth
      substrate.
AB  - In order to understand the attachment mechanism of flies, it is important to
      clarify the question of how the adhesive pad (pulvillus) builds and breaks the
      contact with the substrate. By using normal and high-speed video recordings, the
      present study revealed that pulvilli are positioned on the surface in a
      particular way. The pulvilli are apparently loaded or pressed upon the substrate
      after leg contact, as evidenced by splaying of the claws. Detachment of pulvilli
      from the substrate may be achieved in four different modes depending on the leg
      (fore-, mid- or hindleg): pulling, shifting, twisting, and lifting. Lifting is
      the only detachment mode depending on the claws' action. Kinematics of the tarsal
      chain is studied in leg preparations, in which the tendon of the claw flexor
      muscle was pulled by tweezers and video recorded. The morphological background of
      tarsal movements during attachment and detachment is studied by scanning electron
      microscopy, fluorescent microscopy, and bright field light microscopy followed by
      serial semithin sectioning of pretarsal structures. Several resilin-bearing
      springs are involved in the recoil of the tarsal segments to their initial
      position, when the tendon is released after pull.

PMID- 12804722
TI  - The visual system of the honeybee (Apis mellifera): the maximum length of the
      orientation detector.
AB  - Bees were trained to discriminate between two or more black bars and similar bars
      at right angles, presented on a vertical surface. The positions of the bars were
      shifted every 5 min to prevent their locations being used as cues. The
      experiments exploit the fact that bees do not discriminate the global orientation
      of a straight line of small black squares that are individually resolved, because
      the local responses to equal lengths of edges at right angles cancel out, and
      each square has no residual orientation cue. The experiments measure the
      resolution of this effect by control of the width of the gaps between the
      squares. At the limit the unit orientation detectors cannot span the gaps.
      Training with vertical or with horizontal bars in separate experiments, and
      testing with vertical or horizontal lines of squares, shows that the vertical
      gaps in horizontal rows are detected with better resolution than horizontal gaps
      in vertical rows. The results show that unit orientation detectors span not more
      than 3 ommatidia.

PMID- 12804723
TI  - Relation of mortality of primary angioplasty during acute myocardial infarction
      to door-to-Thrombolysis In Myocardial Infarction (TIMI) time.
AB  - For primary angioplasty of acute myocardial infarction (AMI), the relation of
      treatment benefit and time has been debated. The present study aimed to evaluate,
      in a single-center cohort of patients with ST-segment elevation AMI, which time
      intervals were carefully and consistently measured, and the relations among
      ischemic time, in-hospital delays, and in-hospital survival. We included 499
      patients (mean age 59 years; 80% men) who underwent successful primary
      percutaneous transluminal coronary angioplasty (PTCA) for AMI admitted < or =6
      hours after symptom onset. The population was divided into tertiles with respect
      to time between onset of symptoms and admission, onset of symptoms to
      Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow, and time from
      admission to TIMI grade 3 flow. Univariate analysis followed by multiple logistic
      regression was performed using the variables linked to mortality in the
      univariate analysis to assess the relation between predictor variables and in
      hospital mortality. The in-hospital mortality rate was 3.2%. There was no
      significant relation between the various tertiles of time intervals and in
      hospital mortality. After linear logistic regression, only age (odds ratio [OR]
      1.79 per 10 years), female gender (OR 3.56), and door-to-TIMI 3 time (OR 1.27 per
      15 minutes) were independently correlated with in-hospital mortality.

PMID- 12804724
TI  - Individual prediction of functional recovery after coronary revascularization in
      patients with ischemic cardiomyopathy: the scar-to-biphasic model.
AB  - Currently, the prediction of improvement of left ventricular (LV) ejection
      fraction (EF) after revascularization in patients with ischemic cardiomyopathy
      relies only on viable myocardium extent, whereas both the amount of viable and
      scar tissue may be important. A model was developed, based on the amount of
      viable and nonviable myocardium, to predict functional recovery. Viable and
      scarred myocardium was defined by dobutamine stress echocardiography (DSE) in 108
      consecutive patients. LVEF before and 9 to 12 months after revascularization was
      assessed by radionuclide ventriculography; an improvement of > or =5% was
      considered significant. In the 1,089 dysfunctional segments (63%), DSE elicited
      biphasic response in 216 segments (20%), sustained improvement in 205 (19%),
      worsening in 43 (4%), and no change in 625 (57%). LVEF improved in 39 patients
      (36%). Only the numbers of biphasic and scar segments were predictors of
      improvement or no improvement of LVEF (odds ratio 1.5, 95% confidence interval
      1.2 to 1.7, p <0.0001 for biphasic segments; odds ratio 0.8, 95% confidence
      interval 0.7 to 0.9, p <0.0005 for scarred segments). The sustained improvement
      and worsening pattern were not predictive of improvement or no improvement. A
      regression function, based on the number of scar and biphasic segments, showed
      that the likelihood of recovery was 85% in patients with extensive biphasic
      tissue and no scars and 11% in patients with extensive scars and no biphasic
      myocardium. Patients with a mixture of scar and biphasic tissue had an
      intermediate likelihood of improvement (50%). In patients with ischemic
      cardiomyopathy and a mixture of viable and nonviable tissue, both numbers of
      viable and nonviable segments should be considered to accurately predict
      functional recovery after revascularization.

PMID- 12804725
TI  - Value of definitive diagnostic testing in the evaluation of patients presenting
      to the emergency department with chest pain.
AB  - The optimal diagnostic evaluation of patients presenting to the emergency
      department (ED) with chest pain but without myocardial infarction or unstable
      angina is controversial. We performed a prospective, nonrandomized, observational
      study of 1,195 consecutive patients presenting to the ED with chest pain but who
      had normal or nondiagnostic electrocardiograms and negative cardiac biomarkers.
      Patients (mean +/- SD age 61 +/- 15 years; 55% women) were admitted to the
      hospital and a standard protocol for evaluation and treatment was suggested. The
      use of stress myocardial perfusion imaging (MPI) or cardiac catheterization
      during their index hospitalization, and the 3-month incidence of coronary
      angiography, percutaneous cardiac intervention, coronary artery bypass surgery,
      re-presentation to our institution's ED for chest pain, myocardial infarction, or
      death were followed. Five hundred nine of 1,195 patients (43%) underwent
      provocative stress MPI during their index hospitalization; 37% had perfusion
      defects (predominantly ischemia). Fifty-six of 1,195 patients (4%) underwent
      cardiac catheterization without stress MPI for their primary diagnostic
      evaluation. Six hundred thirty of 1,195 patients (53%) had neither MPI or cardiac
      catheterization during their index hospitalization. During the 3-month follow-up
      period, patients with a normal stress perfusion study during their index
      hospitalization had fewer return visits (4%) compared with patients with abnormal
      perfusion studies (19%), those who underwent catheterization directly (16%), or
      patients with no initial diagnostic evaluation (15%) (p <0.001). In addition,
      patients who had a diagnostic evaluation during their index hospitalization had a
      lower incidence of either acute myocardial infarction (0.9% vs 2.1%) or death
      (0.4% vs 3.0%, p <0.001) in the 3-month follow-up period. Accordingly, we
      strongly advocate provocative stress MPI early after presentation for chest pain
      in all patients with risk factors for coronary artery disease.

PMID- 12804726
TI  - Prediction of functional recovery of hibernating myocardium using harmonic power
      Doppler imaging and dobutamine stress echocardiography in patients with coronary
      artery disease.
AB  - The aim of this study was to compare the accuracy of harmonic power Doppler
      imaging (HPDI) and dobutamine stress echocardiography (DSE) in predicting
      recovery of myocardial function after bypass surgery. HPDI using triggering
      imaging with the administration of Levovist (Shering AG, Berlin, Germany) and DSE
      were performed in 34 patients (mean age 64 +/- 5 years) with left ventricular
      dysfunction. A repeat echocardiogram at rest was performed 3 months after
      revascularization. Of the 408 revascularized dysfunctional segments, 188 (45%)
      improved on the repeat echocardiogram. HPDI exhibited overall similar sensitivity
      (88% vs 87%) and accuracy (74% vs 79%) but lower specificity (61% vs 72%, p<0.05)
      compared with DSE for predicting recovery of myocardial function. Only delayed
      opacification at the 1:8 triggering point, demonstrated in 62% of viable
      segments, exhibited higher sensitivity (63%) and positive (58%) and negative
      (66%) predictive values than early opacification at 1:4 (25%, p<0.001; 35%,
      p<0.001; and 49%, p<0.001, respectively) in predicting functional recovery. The
      presence of contrast enhancement within the revascularized area resulted in a
      significant improvement after revascularization in wall motion score index and
      ejection fraction compared with areas with residual contrast defect (1.9 +/- 0.3
      vs 2.3 +/- 0.3, p<0.01; 36 +/- 6% vs 29 +/- 5%, p<0.01, respectively).
      Significant correlations were observed between the contrast score index and the
      follow-up wall motion score index (r = -0.67) and between the contrast score
      index and the follow-up ejection fraction change (r = 0.65). Triggered HPDI has
      high sensitivity in detecting hibernating myocardium and can accurately predict
      the potential for recovery of ischemic left ventricular dysfunction 3 months
      after revascularization.

PMID- 12804727
TI  - Preventing coronary events by optimal control of blood pressure and lipids in
      patients with the metabolic syndrome.
AB  - We estimated the coronary heart disease (CHD) events that are preventable by
      treatment of lipids and blood pressure in patients with metabolic syndrome
      (MetS), a contributor to coronary heart disease (CHD). Among patients aged 30 to
      74 years (without diabetes or CHD) in the United States, MetS was defined by
      National Cholesterol Education Program criteria. CHD events over a period of 10
      years were estimated by Framingham algorithms. Events that could be prevented by
      statistically "controlling" blood pressure, low-density lipoprotein (LDL)
      cholesterol, and high-density lipoprotein (HDL) cholesterol to either normal or
      optimal levels according to national guidelines were calculated. Of 7.5 million
      men and 9.0 million women aged 30 to 74 years with MetS, approximately 1.5
      million men and 0.45 million women, if untreated, developed CHD events in 10
      years. In men and women, blood pressure control to normal levels "prevented"
      28.1% and 12.5% of CHD events, respectively (p <0.01); control to optimal levels
      resulted in preventing 28.2% and 45.2% of events, respectively (p <0.01). Control
      of HDL cholesterol to normal levels resulted in preventing 25.3% of events in men
      and 27.3% in women; optimal control prevented 51.2% and 50.6% of events,
      respectively. Control of LDL cholesterol to normal levels prevented 9.3% of
      events in men and 9.8% of events in women; control to optimal levels prevented
      46.2% and 38.1% of events (p <0.05), respectively. Control of all 3 risk factors
      to normal levels resulted in preventing 51.3% of events for men and 42.6% for
      women; control to optimal levels resulted in preventing 80.5% and 82.1% of
      events, respectively. Thus, many CHD events in patients with MetS may be
      preventable by nominal or optimal control of lipids and/or blood pressure.

PMID- 12804728
TI  - Effectiveness of aggressive management of dyslipidemia in a collaborative-care
      practice model.
AB  - The Cardiovascular Risk Identification and Treatment Center was established in
      1997, adopting a collaborative-care clinic model for the purpose of improving the
      management of high-risk patients with dyslipidemia. This was a retrospective
      analysis of 417 high-risk patients with > or =1 year of follow-up laboratory
      data. Analysis included changes in total cholesterol, low-density lipoprotein
      (LDL), high-density lipoprotein (HDL), non-HDL, triglycerides, and total
      cholesterol to HDL ratio; lipoprotein goal achievement; Framingham risk score;
      liver function; and cardiovascular events. At baseline, 66% of patients had
      coronary heart disease (CHD) or equivalent risk, 45% were not receiving
      dyslipidemia therapy, and 29% were on statin monotherapy. After 3 years in the
      program, 56% were receiving combination therapy, 41% were on monotherapy, and 2%
      were not on therapy. The 3 most common treatment regimens were statin plus niacin
      (36%), statin alone (22%), and niacin alone (14%). All lipoproteins improved from
      baseline (p <0.001). Overall, 62% to 74% of patients reached singular lipid goals
      and 35% achieved combined lipid goals. Patients with Framingham 10-year CHD risk
      of >20% were reduced from 6% to <1%. Only 29 patients (7.0%) had a cardiovascular
      event, including 5 (1.0%) who experienced a myocardial infarction. Aspartate
      aminotransferase/alanine transferase elevation >3 times normal occurred in 1% of
      patients. In conclusion, a collaborative-care practice model adopting
      individualized, aggressive pharmacologic and nonpharmacologic treatment
      strategies is highly effective in achieving lipid goals, is sustainable, and is
      safe. Furthermore, this approach yields reduced projected 10-year CHD risk. A low
      rate of cardiovascular events was observed.

PMID- 12804729
TI  - Effects of extended-release niacin on lipoprotein subclass distribution.
AB  - The efficacy of extended-release niacin (niacin ER) on lipoprotein subclasses was
      evaluated in patients with primary hypercholesterolemia using a proton nuclear
      magnetic resonance method. Paired plasma samples collected at baseline and after
      12 weeks' treatment with niacin ER 1,000 (n = 21) or 2,000 (n = 20) mg/day or
      placebo (n = 19) were available for 60 eligible patients from a previous
      multicenter, randomized, controlled trial. Niacin ER increased high-density
      lipoprotein (HDL) cholesterol and decreased low-density lipoprotein (LDL)
      cholesterol and very low-density lipoprotein triglycerides in a dose-dependent
      manner relative to placebo. Niacin ER increased large HDL particles (H5 and H4,
      corresponding to the HDL(2ab) fraction) without having a net effect on small HDL
      particles (H3, H2, and H1, corresponding to the HDL(3abc) fraction). It also
      decreased smaller, denser LDL particles (L1 and L2) and increased the larger,
      more buoyant L3 subclass. The inhibitory effect of niacin ER on very low-density
      lipoprotein was evident on the larger particles (V6, V5, V4, and V3 subclasses)
      rather than the smaller ones (V2 and V1). The results show that niacin ER
      produces a beneficial effect on lipoprotein subclasses, specifically decreasing
      the more atherogenic small, dense LDL particles and enhancing the
      cardioprotective large HDL particles.

PMID- 12804730
TI  - Safety and feasibility of a clinical pathway for the outpatient initiation of
      antiarrhythmic medications in patients with atrial fibrillation or atrial
      flutter.
AB  - We sought to establish the safety and feasibility of a clinical pathway for the
      outpatient initiation of antiarrhythmic medications (AAMs) for the maintenance of
      sinus rhythm in patients with atrial fibrillation (AF) or atrial flutter (AFl).
      AAMs are frequently utilized to maintain sinus rhythm in patients with AF or AFl.
      Although they are often initiated in an outpatient setting, there is little
      prospective evidence for the safety of this approach. Patients with a history of
      AF or AFl were prospectively monitored with an event recorder during 409 AAM
      initiation trials. All AAMs were initiated in sinus rhythm. Patients transmitted
      a recording (30 seconds) once daily for 10 consecutive days. Amiodarone was used
      for 212 patients (51.8%), 127 (31.1%) received a type 1C AAM, 37 (9.0%) received
      sotalol, and 33 (8.1%) received a type 1A AAM. Adverse events occurred in 17
      patients (3 died, 3 had bradycardia that required permanent pacemaker
      implantation, and 11 had bradycardia requiring a decrease in the dose of
      antiarrhythmic or rate-controlling medication). Most events were due to
      bradycardia in patients who received amiodarone. There was a significant
      association between amiodarone-associated bradycardia and women. The only event
      that occurred during the first 48 hours was an episode of bradycardia in a
      patient who received amiodarone and was managed as an outpatient. The outpatient
      initiation of AAMs for patients with a history of AF or AFl while in sinus rhythm
      is associated with significant risk. Most adverse events occurred beyond the
      usual time period for in-hospital monitoring of the initiation of AAMs.

PMID- 12804731
TI  - Andrew Peter Selwyn, MD: a conversation with the editor.

PMID- 12804732
TI  - Usefulness of creatinine clearance in predicting early and late death after
      primary angioplasty for acute myocardial infarction.

PMID- 12804733
TI  - Comparison of impact of emergency percutaneous revascularization on outcome of
      patients > or =75 to those < 75 years of age with acute myocardial infarction
      complicated by cardiogenic shock.

PMID- 12804734
TI  - Early direct coronary angioplasty in survivors of out-of-hospital cardiac arrest.

PMID- 12804735
TI  - Comparison of the QuickSeal Femoral Arterial Closure System with manual
      compression following diagnostic and interventional catheterization procedures.

PMID- 12804736
TI  - Effect of gender on outcomes of acute coronary syndromes.

PMID- 12804737
TI  - Association between initial QRS duration and no-reflow phenomenon in patients
      with acute left main coronary artery obstruction.

PMID- 12804738
TI  - Prognostic significance of heart rate turbulence in patients undergoing coronary
      artery bypass grafting.

PMID- 12804739
TI  - Usefulness of carotid intimal medial thickness and flow-mediated dilation in a
      preventive cardiovascular practice.

PMID- 12804740
TI  - Left atrial size and function after spontaneous cardioversion of atrial
      fibrillation and their relation to N-terminal atrial natriuretic peptide.

PMID- 12804741
TI  - Anatomic description of Bachmann's bundle and its relation to the atrial septum.

PMID- 12804742
TI  - Comparison of single premature versus continuous overdrive stimulation for
      identification of a protected isthmus in macro-reentrant atrial tachycardia
      circuits.

PMID- 12804743
TI  - Is left ventricular postsystolic long-axis shortening a marker for severity of
      hypertensive heart disease?

PMID- 12804744
TI  - Comparison of T-wave alternans testing during treadmill and bicycle exercise in
      patients with congestive heart failure.

PMID- 12804745
TI  - QT dispersion after beta-blocker therapy (carvedilol or metoprolol) in children
      with heart failure.

PMID- 12804746
TI  - Comparison of frequency of active infective endocarditis by echocardiography in
      patients with bacteremia with and without human immunodeficiency virus.

PMID- 12804747
TI  - Association of asymmetric pulmonary artery growth following palliative surgery
      for hypoplastic left heart syndrome with ductal coarctation, neoaortic arch
      compression, and shunt-induced pulmonary artery stenosis.

PMID- 12804748
TI  - Choices physicians would make if they were the parents of a child with
      hypoplastic left heart syndrome.

PMID- 12804749
TI  - Effect of a multicomponent, ephedra-containing dietary supplement (Metabolife
      356) on Holter monitoring and hemostatic parameters in healthy volunteers.

PMID- 12804750
TI  - Relation of hemoglobin A1c to left ventricular relaxation in patients with type 1
      diabetes mellitus and without overt heart disease.

PMID- 12804751
TI  - Prevalence, etiology, and outcome of patients with restrictive left ventricular
      filling and relatively preserved systolic function.

PMID- 12804752
TI  - A new device for automatic measurements of arterial stiffness and ankle-brachial
      index.

PMID- 12804753
TI  - Comparison between phase-velocity cine magnetic resonance imaging and invasive
      oximetry for quantification of atrial shunts.

PMID- 12804755
TI  - Low-density lipoprotein cholesterol and post-myocardial infarction depression.

PMID- 12804756
TI  - Are syn-ligated (bacterio)chlorophyll dimers energetic traps in light-harvesting
      systems?
AB  - A recent study of the stereochemical details of chlorophyll ligation in
      photosystem I [Balaban et al., Biochim. Biophys. Acta 1556 (2002) 197-207] has
      revealed that only 14 chlorophylls out of the total 96 are ligated from the same
      side (syn) as the 17-propionic acid residue which is esterified with phytol. The
      syn chlorophylls are carefully surrounding the reaction center forming the inner
      core antenna system and their ligands have been strongly conserved in several
      species during evolution. We hypothesize here that the two dimers of closely
      spaced syn chlorophylls which are encountered within roughly 2 nm of P700 are the
      ultimate energetic traps of this light-harvesting system. Structurally very
      similar bacteriochlorophyll a dimers are encountered within the Fenna-Matthews
      Olson protein complex and within the B850 ring of the LH2 complex of purple
      bacteria. The non-random disposal of these dimers lends support to our hypothesis
      that the syn ligation coupled with a strong excitonic interaction leads to the
      most red-shifted pigments in light-harvesting systems. We would like to encourage
      both theoretical and experimental studies to either prove or disprove this
      intriguing structure-function conjecture in view of designing efficient
      artificial light-harvesting systems.

PMID- 12804757
TI  - Adiponectin represents an independent cardiovascular risk factor predicting serum
      HDL-cholesterol levels in type 2 diabetes.
AB  - Low levels of high-density lipoprotein (HDL)-cholesterol represent an independent
      cardiovascular risk factor and, besides reduced physical activity, mechanisms
      leading to decreased HDL-cholesterol levels are not known. We aimed to test the
      hypothesis, that adiponectin provides a missing link between type 2 diabetes and
      low levels of HDL-cholesterol, independent from common metabolic risk factors.
      523 patients with type 2 diabetes were investigated for adiponectin serum levels
      and parameters of lipid metabolism. Even after correction for age, gender, BMI
      and fasting insulin concentration, serum levels of adiponectin were highly
      significant (P<0.0001) and positively (regression analysis: r=0.86) associated
      with HDL-cholesterol levels in type 2 diabetes. CONCLUSION: adiponectin seems to
      predict HDL-cholesterol levels in patients with diabetes mellitus type 2. Low
      levels of adiponectin are associated with low levels of HDL-cholesterol
      independently from common metabolic risk factors and therefore represent an
      independent cardiovascular risk factor in type 2 diabetes. Thus, adiponectin is a
      potentially new drug target in the treatment of dyslipidaemia.

PMID- 12804758
TI  - Inverse sequence similarity of proteins does not imply structural similarity.
AB  - There is a debate on the folding of proteins with inverted sequences. Theoretical
      approaches and experiments give contradictory results. Many proteins in the
      Protein Data Bank (PDB) show conspicuous inverse sequence similarity (ISS) to
      each other. Here we analyze whether this ISS is related to structural similarity.
      For the first time, we performed a large scale three-dimensional (3-D)
      superposition of corresponding Calpha atoms of forwardly and inversely aligned
      proteins and tested the degree of secondary structure identity between them.
      Comparing proteins of less than 50% pairwise sequence identity, only 0.5% of the
      inversely aligned pairs had similar folds (99 out of 19073), whereas about 9% of
      forwardly aligned proteins in the same score and length range show similar 3-D
      structures (1731 out of 19248). This observation strongly supports the view that
      the inversion of sequences in almost all cases leads to a different folding
      property of the protein. Inverted sequences are thus suitable as protein-like
      sequences for control purposes without relations to existing proteins.

PMID- 12804759
TI  - Phosphatidylserine exposure in Fas type I cells is mitochondria-dependent.
AB  - Previous studies have demonstrated that Fas-triggered activation of effector
      caspases and subsequent nuclear apoptosis either is mitochondria-independent
      (type I cells) or relies on mitochondrial amplification of the initial stimulus
      (type II cells). We show herein that Bcl-2 overexpression in a prototypic type I
      cell line (SKW6.4) promotes mitochondrial generation of ATP and blocks Fas
      triggered plasma membrane externalization of phosphatidylserine (PS). Moreover,
      overexpression of Bcl-2 attenuates macrophage engulfment of Fas-triggered cells.
      Fas-mediated DNA fragmentation, on the other hand, remains unaffected in SKW6.4
      bcl-2 cells. These studies thus demonstrate that PS externalization and clearance
      of cell corpses are mitochondria-dependent events, and show that these events can
      be dissociated from other features of the apoptotic program, in Fas type I cells.

PMID- 12804760
TI  - Alternative splicing of type II procollagen pre-mRNA in chondrocytes is
      oppositely regulated by BMP-2 and TGF-beta1.
AB  - Type II collagen is the major protein of cartilage and is synthesized as a
      procollagen in two forms (IIA and IIB), generated by differential splicing of the
      gene primary transcript. Previous studies have indicated that only type IIB is
      expressed in differentiated chondrocytes. Here, we examined the effects of bone
      morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta1 on the
      expression of IIA and IIB forms expressed in de-differentiated chondrocytes grown
      in monolayer. Our results demonstrate that BMP-2 favors expression of type IIB
      whereas TGF-beta1 potentiates expression of type IIA induced by subculture. These
      observations reveal the specific capability of BMP-2 to reverse the de
      differentiation state of chondrocytes.

PMID- 12804761
TI  - Structural and functional analysis of a lycopene beta-monocyclase gene isolated
      from a unique marine bacterium that produces myxol.
AB  - A gene coding for lycopene beta-monocyclase, which metabolizes lycopene (psi,psi
      carotene) to gamma-carotene (beta,psi-carotene), was isolated for the first time
      from a unique marine bacterium strain P99-3 that produces myxol (a gamma-carotene
      derivative). This lycopene beta-monocyclase gene (designated crtYm) was included
      in the gene cluster which contained carotenoid biosynthetic gene (crtI, crtB,
      crtZ, crtY, and crtA) homologs. CrtYm, the CrtY homolog, metabolized lycopene to
      gamma-carotene, which was confirmed by deletion/expression analysis of the crtYm
      and by subsequent analysis of the metabolites from lycopene based on the
      retention times on high-performance liquid chromatography, UV-visible absorption
      spectra, and mass spectrometry.

PMID- 12804762
TI  - OmpF enhances the ability of BtuB to protect susceptible Escherichia coli cells
      from colicin E9 cytotoxicity.
AB  - The outer membrane (OM) vitamin B(12) receptor, BtuB, is the primary receptor for
      E group colicin adsorption to Escherichia coli. Cell death by this family of
      toxins requires the OM porin OmpF but its role remains elusive. We show that OmpF
      enhances the ability of purified BtuB to protect bacteria against the
      endonuclease colicin E9, demonstrating either that the two OM proteins form the
      functional receptor or that OmpF is recruited for subsequent translocation of the
      bacteriocin. While stable binary colicin E9-BtuB complexes could be readily shown
      in vitro, OmpF-containing complexes could not be detected, implying that OmpF
      association with the BtuB-colicin complex, while necessary, must be weak and/or
      transient in nature.

PMID- 12804763
TI  - Activity of coliphage HK022 excisionase (Xis) in the absence of DNA binding.
AB  - A mutated excisionase (Xis) protein of coliphage HK022 whose single Cys residue
      was replaced by Ser does not bind to its two tandem binding sites (X1, X2) on the
      P arm of attR. Despite its DNA-binding inability the protein showed 30% excision
      activity of the wild type Xis both in vitro and in vivo. This partial activity is
      attributed to the interaction of Xis with integrase that is retained in the
      mutant protein. This protein-protein interaction occurs in the absence of DNA
      binding.

PMID- 12804764
TI  - Motilin-bicelle interactions: membrane position and translational diffusion.
AB  - The interaction between the peptide hormone motilin and bicelles has been
      investigated by pulsed field gradient-nuclear magnetic resonance methods and by
      the use of paramagnetic probes. Diffusion coefficients were measured for motilin,
      the phospholipids with and without motilin, and for tetramethylsilane. The
      results show that around 90% of motilin is bound to acidic bicelles and 84% of
      motilin is bound to neutral bicelles. It is found that the apparent bicelle size
      is reduced by the presence of motilin. This cannot be explained by changes in 1,2
      dihexanoyl-sn-glycero-3-phosphatidylcholine solubility. The use of paramagnetic
      agents to investigate the position of motilin shows that the turn in the N
      terminus of motilin is inserted into the bicelle, while the helix most likely
      resides within the head-group layer.

PMID- 12804765
TI  - Modulation of the classical multidrug resistance (MDR) phenotype by RNA
      interference (RNAi).
AB  - For reversal of MDR1 gene-dependent multidrug resistance (MDR), two small
      interfering RNA (siRNA) constructs were designed to inhibit MDR1 expression by
      RNA interference. SiRNA duplexes were used to treat human pancreatic carcinoma
      (EPP85-181RDB) and gastric carcinoma (EPG85-257RDB) cells. In both cellular
      systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA
      and protein levels. Resistance against daunorubicin was decreased to 89% (EPP85
      181RDB) or 58% (EPG85-257RDB). The data indicate that this approach may be
      applicable to cancer patients as a specific means to reverse tumors with a P
      glycoprotein-dependent MDR phenotype back to a drug-sensitive one.

PMID- 12804766
TI  - The PEF family proteins sorcin and grancalcin interact in vivo and in vitro.
AB  - The penta-EF hand (PEF) family of calcium binding proteins includes grancalcin,
      peflin, sorcin, calpain large and small subunits as well as ALG-2. Systematic
      testing of the heterodimerization abilities of the PEF proteins using the yeast
      two-hybrid and glutathione S-transferase pull-down assays revealed the new
      finding that grancalcin interacts strongly with sorcin. In addition, sorcin and
      grancalcin can be co-immunoprecipitated from lysates of human umbilical vein
      endothelial cells. Our results indicate that heterodimerization, in addition to
      differential interactions with target proteins, might be a way to regulate and
      fine tune processes mediated by calcium binding proteins of the penta-EF hand
      type.

PMID- 12804767
TI  - Pharmacological analysis of a dopamine D(2Short):G(alphao) fusion protein
      expressed in Sf9 cells.
AB  - A dopamine D(2Short) receptor:G(alphao) fusion protein was expressed in Sf9 cells
      using the baculovirus expression system. [(3)H]Spiperone bound to
      D(2Short):G(alphao) with a pK(d) approximately 10. Dopamine stimulated the
      binding of [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) to
      D(2Short):G(alphao) expressed with Gbeta(1)gamma(2) (E(max)>460%; pEC(50) 5.43+/
      0.06). Most of the putative D(2) antagonists behaved as inverse agonists
      (suppressing basal [(35)S]GTPgammaS binding) at
      D(2Short):G(alphao)/Gbeta(1)gamma(2) although (-)-sulpiride and ziprasidone were
      neutral antagonists. Competition of [(3)H]spiperone binding by dopamine and 10,11
      dihydroxy-N-n-propylnorapomorphine revealed two binding sites of different
      affinities, even in the presence of GTP (100 micro M). The D(2Short):G(alphao)
      fusion protein is therefore a good model for characterising D(2) receptors.

PMID- 12804768
TI  - Occludin phosphorylation: identification of an occludin kinase in brain and cell
      extracts as CK2.
AB  - In epithelial and endothelial cells, tight junctions limit paracellular flux of
      ions, proteins and other macromolecules. However, mechanisms regulating tight
      junction function are not clear. Occludin, a tight junction protein, undergoes
      phosphorylation changes in several situations but little is known about occludin
      kinases. A recombinant C-terminal fragment of occludin is a substrate for a
      kinase in crude extracts of brain. This activity was purified about 10000-fold
      and identified as CK2 (casein kinase 2) by peptide mass fingerprinting,
      immunoblotting and mutation of CK2 sites within the occludin sequence. CK2 is
      therefore a candidate kinase for regulation of occludin phosphorylation in vivo.

PMID- 12804769
TI  - Mitochondria-derived glutamate at the interplay between branched-chain amino acid
      and glucose-induced insulin secretion.
AB  - In pancreatic beta-cells, glutamate has been proposed to mediate insulin
      secretion as a glucose-derived factor, although it is also considered for its
      sole catabolic function. Hence, changes in cellular glutamate levels are a matter
      of debate. Here, we investigated the effects of glucose and the glutamate
      precursor glutamine on kinetics of glutamate levels together with insulin
      secretion in INS-1E beta-cells. Preincubation at low (1 mM) glucose resulted in
      reduced cellular glutamate levels, which were doubled by exposure to glutamine.
      In glutamine-deprived cells, 5 mM glucose restored glutamate concentrations.
      Incubation at 15 mM glucose increased cellular glutamate, along with stimulation
      of insulin secretion, following both glutamine-free and glutamine-rich
      preincubations. Nuclear magnetic resonance (NMR) spectroscopy of INS-1E cells
      exposed to 15 mM D-[1-(13)C]glucose revealed glutamate as the major glucose
      metabolic product. Branched-chain amino acids, such as leucine, reduced cellular
      glutamate levels at low and intermediate glucose. This study demonstrates that
      glucose stimulates glutamate generation, whereas branched-chain amino acids
      promote competitive glutamate expenditure.

PMID- 12804770
TI  - Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway.
AB  - We studied the effects of fibroblast growth factor (FGF-10) on alveolar
      epithelial cell (AEC) Na,K-ATPase regulation. Within 30 min FGF-10 increased Na,K
      ATPase activity and alpha1 protein abundance by 2.5-fold at the AEC plasma
      membrane. Pretreatment of AEC with the mitogen-activated protein kinase (MAPK)
      inhibitor U0126, a Grb2-SOS inhibitor (SH3-b-p peptide), or a Ras inhibitor
      (farnesyl transferase inhibitor (FTI 277)), as well as N17-AEC that express a Ras
      dominant negative protein each prevented FGF-10-mediated Na,K-ATPase recruitment
      to the AEC plasma membrane. Accordingly, we provide first evidence that FGF-10
      upregulates (short-term) the Na,K-ATPase activity in AEC via the Grb2
      SOS/Ras/MAPK pathway.

PMID- 12804771
TI  - Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma
      signaling by inhibiting STAT1 and STAT2 phosphorylation.
AB  - Measles virus (MV), a member of the family Paramyxoviridae, encodes C and V non
      structural proteins. To clarify the functions of MV C and V proteins, HeLa cell
      lines constitutively expressing C or V protein were established. We found that
      expression of V protein inhibited interferon (IFN)-alpha/beta signaling but not
      IFN-gamma signaling. C protein had no inhibitory effect on IFN signaling in our
      experimental condition. Degradation of selective signal transducers and
      activators of transcription (STAT) proteins was not observed in HeLa cells
      expressing V protein. In contrast, tyrosine phosphorylation of both STAT1 and
      STAT2 was inhibited in these cells after IFN-beta stimulation.

PMID- 12804772
TI  - In vitro DNA-binding properties of VirB, the Shigella flexneri virulence
      regulatory protein.
AB  - The DNA-binding activity of the Shigella flexneri VirB transcription factor was
      studied in vitro. The protein was found to bind non-specifically to DNA, but
      showed preferential binding to VirB-dependent promoter sequences. DNA binding was
      contingent on the presence of an intact helix-turn-helix motif. While high
      molecular mass protein-DNA complexes were formed in both specific and non
      specific interactions with DNA, mutant derivatives of VirB lacking a leucine
      zipper domain or a carboxyl-terminal-located oligomerisation domain formed
      discrete complexes, indicating that an ability to oligomerise on DNA was
      responsible for the formation of high molecular mass complexes by the wild-type
      protein.

PMID- 12804773
TI  - Evidence linking the Pseudomonas oleovorans alkane omega-hydroxylase, an integral
      membrane diiron enzyme, and the fatty acid desaturase family.
AB  - Pseudomonas oleovorans alkane omega-hydroxylase (AlkB) is an integral membrane
      diiron enzyme that shares a requirement for iron and oxygen for activity in a
      manner similar to that of the non-heme integral membrane desaturases, epoxidases,
      acetylenases, conjugases, ketolases, decarbonylase and methyl oxidases. No
      overall sequence similarity is detected between AlkB and these desaturase-like
      enzymes by computer algorithms; however, they do contain a series of histidine
      residues in a similar relative positioning with respect to hydrophobic regions
      thought to be transmembrane domains. To test whether these conserved histidine
      residues are functionally equivalent to those of the desaturase-like enzymes we
      used scanning alanine mutagenesis to test if they are essential for activity of
      AlkB. These experiments show that alanine substitution of any of the eight
      conserved histidines results in complete inactivation, whereas replacement of
      three non-conserved histidines in close proximity to the conserved residues,
      results in only partial inactivation. These data provide the first experimental
      support for the hypotheses: (i) that the histidine motif in AlkB is equivalent to
      that in the desaturase-like enzymes and (ii) that the conserved histidine
      residues play a vital role such as coordinating the Fe ions comprising the diiron
      active site.

PMID- 12804774
TI  - Proton release upon oxidation of tyrosine in reaction centers from Rhodobacter
      sphaeroides.
AB  - Markedly different light-induced protonational changes were measured in two
      reaction center mutants of Rhodobacter sphaeroides. A quadruple mutant containing
      alterations, at residues L131, M160, M197, and M210, that elevate the midpoint
      potential of the bacteriochlorophyll dimer was compared to the Y(M) mutant, which
      contains these alterations plus a tyrosine at M164 serving as a secondary
      electron donor [Kalman et al., Nature 402 (1999) 696]. In the quadruple mutant, a
      proton uptake of 0.1-0.3 H(+)/reaction center between pH 6 and 10 resulted from
      formation of the oxidized bacteriochlorophyll donor and reduced primary quinone.
      In the Y(M) mutant, a maximal proton release of -0.5 H(+)/reaction center at pH 8
      was attributed to formation of the tyrosyl radical and modeled using
      electrostatic and direct proton-releasing mechanisms.

PMID- 12804775
TI  - Pellino2 activates the mitogen activated protein kinase pathway.
AB  - Engagement of the interleukin-1 (IL1) and Toll receptors, which are part of the
      innate immune system, facilitates activation of the transcription factors NF
      kappaB, Elk-1 and AP-1. Pellino1 and Pellino2 have recently been shown to be
      intermediates in the pathway leading to activation of NF-kappaB. Here we
      demonstrate for the first time that human Pellino2 interacts with TRAF6 (tumor
      necrosis factor receptor associated factor 6) and that both Pellino1 and Pellino2
      also interact with TAK1 (transforming growth factor-beta activated kinase 1). We
      also show that Pellino2, but not Pellino1, can activate the mitogen activated
      protein kinase pathway leading to activation of AP-1 and Elk-1. These
      observations suggest a role for the Pellino proteins in the IL1/Toll signaling
      cascades as scaffold proteins that may regulate signaling branch-points.

PMID- 12804776
TI  - PTEN modulates insulin-like growth factor II (IGF-II)-mediated signaling; the
      protein phosphatase activity of PTEN downregulates IGF-II expression in hepatoma
      cells.
AB  - The PTEN gene (phosphatase and tensin homologous on chromosome 10) is frequently
      mutated or deleted in a number of malignancies including human hepatocellular
      carcinoma (HCC). We reported previously that the hepatitis B virus X (HBx)
      protein, known to be a causative agent in the formation of HCC, activates insulin
      like growth factor II (IGF-II) expression through Sp1 phosphorylation by protein
      kinase C (PKC) or mitogen-activated protein kinase (MAPK) signaling. In this
      report we demonstrate that the PTEN effect on HBx induced IGF-II activation in a
      hepatoma cell line. Expression of PTEN and IGF-II was inversely related in
      different hepatoma cell lines. PTEN expression induced decreased Sp1 DNA binding
      by dephosphorylating Sp1 and interfered with transcriptional transactivation of
      IGF-II by HBx in hepatoma cells. The protein phosphatase activity was involved in
      PTEN downregulation of IGF-II transcription through downregulation of MAPK, MAPK
      kinase phosphorylation and PKC translocation. Our data suggest that PTEN blocks
      Sp1 phosphorylation in response to HBx, by inactivating PKC, MAPK and MAPK kinase
      which eventually downregulate IGF-II expression, during the formation of HCC.

PMID- 12804777
TI  - Drosophila chk2 plays an important role in a mitotic checkpoint in syncytial
      embryos.
AB  - Drosophila chk2 (Dmchk2, also called Dmnk) plays a crucial role in the DNA damage
      response pathway mediating cell cycle arrest and apoptosis [Xu et al., FEBS Lett.
      508 (2001) 394-398; Peters et al., Proc. Natl. Acad. Sci. USA 99 (2002) 11305
      11310]. In this study, the role of Dmchk2 in early embryogenesis was
      investigated. In the absence of Dmchk2 function, abnormal nuclei accumulate in
      the cortex of the syncytial embryo. We show that the abnormal nuclei result from
      a failure of chromosome segregation probably due to damaged or incomplete
      replicated DNA. Importantly, this Dmchk2 phenotype is partially suppressed by
      reducing the gene dosage of polo or stg. As Polo-like kinase was shown to
      colocalize and coimmunoprecipitate with Chk2 [Tsvetkov et al., J. Biol. Chem. 278
      (2003) 8468-8475] in mammals, these observations suggest that polo might be a key
      target of Dmchk2 in regulating mitotic entry in response to DNA damage or
      replication block.

PMID- 12804778
TI  - The R1 subunit of herpes simplex virus ribonucleotide reductase has chaperone
      like activity similar to Hsp27.
AB  - HSV-2 R1, the R1 subunit of herpes simplex virus (HSV) ribonucleotide reductase,
      protects cells against apoptosis. Here, we report the presence in HSV-2 R1 of a
      stretch exhibiting similarity to the alpha-crystallin domain of the small heat
      shock proteins, a domain known to be important for oligomerization and
      cytoprotective activities of these proteins. Also, the HSV-2 R1 protein, which
      forms multimeric structures in the absence of nucleotide, displayed chaperone
      ability as good as Hsp27 in a thermal denaturation assay using citrate synthase.
      In contrast, mammalian R1, which does not contain an alpha-crystallin domain, has
      neither chaperone nor anti-apoptotic activity. Thus, we propose that the
      chaperone activity of HSV-2 R1 could play an important role in viral
      pathogenesis.

PMID- 12804779
TI  - High glucose potentiates palmitate-induced NO-mediated cytotoxicity through
      generation of superoxide in clonal beta-cell HIT-T15.
AB  - Prolonged exposure to free fatty acids induces beta-cell cytotoxicity. We
      investigated whether this fatty-acid-induced cytotoxicity is affected by high
      glucose levels. In clonal beta-cell HIT-T15, palmitate-induced cytotoxicity was
      potentiated depending on elevated glucose concentrations due to increased
      apoptosis without cytotoxic effects of high glucose per se. This palmitate
      cytotoxicity was blocked by NO synthase inhibitors, and palmitate actually
      increased cellular NO production. The potentiation of palmitate cytotoxicity
      under high glucose was reversed by decreasing superoxide production, suggesting
      that superoxide overproduction under high glucose enhances NO-mediated
      cytotoxicity in beta-cells, which may explain the mechanism of synergistic
      deterioration of pancreatic beta-cells by free fatty acids and high glucose.

PMID- 12804780
TI  - pH dependence studies provide insight into the structure and mechanism of thimet
      oligopeptidase (EC 3.4.24.15).
AB  - Thimet oligopeptidase (EC 3.4.24.15; TOP) is a Zn(II) endopeptidase implicated in
      physiological regulation of processes involving neuropeptides. The present study
      clarifies the active site structure and mechanism of catalysis of TOP. The enzyme
      exhibited a bell-shaped pH dependence of activity having an acidic limb due to a
      protonation event with a pK(a) of 5.7 and a basic limb with pK(a) of 8.8. The
      acidic limb can be attributed to protonation of a residue affecting k(cat) while
      the alkaline limb may be due to conformational change. Mutation of Tyr612 to Phe
      resulted in more than 400-fold decrease in activity. This result, supported by
      modeling studies, implicates Tyr612 in transition state stabilization analogous
      to the role of His231 of thermolysin.

PMID- 12804781
TI  - Misfolded plant virus proteins: elicitors and targets of ubiquitylation.
AB  - Mutant tobacco mosaic virus (TMV) coat proteins (CPs) with known amino acid
      replacements provide well defined examples of destabilized tertiary structures.
      Here we show that misfolded TMV CPs, but not functional wild-type CPs, induce
      massive ubiquitylation in tobacco cells and that denatured, insoluble CP subunits
      are the main substrates of ubiquitin conjugation. As TMV CPs can be easily
      manipulated they are unique tools to study the molecular basis of the plant
      cell's response to aberrant protein structures and the associated intracellular
      stress reactions.

PMID- 12804782
TI  - Functional identification of Gd3+ binding site of metabotropic glutamate receptor
      1alpha.
AB  - We previously reported that the metabotropic glutamate receptor1alpha
      (mGluR1alpha) has a sensitivity to extracellular polyvalent cations such as
      Ca(2+) and Gd(3+) as well as glutamate. Gd(3+) binding site was recently
      identified by crystal structure analysis at the interface of two subunits
      including Glu238, but it remains unknown whether this site is functionally
      involved in the activation of mGluR1alpha by Gd(3+) or not. We analyzed the
      ligand sensitivity of the Glu238Gln mutant, and observed that the sensitivity to
      extracellular Gd(3+) was completely lost, while the sensitivity to glutamate and
      Ca(2+) was not affected. We also observed that the presence of Gd(3+) increased
      the sensitivity of mGluR1alpha to glutamate, and that this effect was again lost
      by Glu238Gln mutation. These results suggest that the binding of Gd(3+) or a
      related endogenous substance to this site, alone or in cooperation with glutamate
      binding at a distant site, leads mGluR1alpha to activation.

PMID- 12804783
TI  - Mutagenesis analysis of the yeast Nha1 Na+/H+ antiporter carboxy-terminal tail
      reveals residues required for function in cell cycle.
AB  - The yeast Nha1 Na(+),K(+)/H(+) antiporter may play an important role in
      regulation of cell cycle, as high-copy expression of the NHA1 gene is able to
      rescue the blockage at the G(1)/S transition of cells lacking Sit4 protein
      phosphatase and Hal3 activities. Interestingly, this function was independent of
      the role of the antiporter in improving tolerance to sodium cations, it required
      the integrity of a relatively large region (from residues 800 to 948) of its
      carboxy-terminal moiety, and was not performed by the fission yeast homolog
      antiporter Sod2, which lacks a carboxy-terminal tail. Here we show that a hybrid
      protein composed of the Sod2 antiporter fused to the carboxy-terminal half of
      Nha1 strongly increased sodium tolerance, but did not allow growth at high
      potassium nor did rescue growth of the sit4 hal3 conditional mutant strain.
      Deletion of Nha1 residues from 800 to 849, 900 to 925 or 926 to 954 abolished the
      function of Nha1 in cell cycle without affecting sodium tolerance. A screening
      for loss-of-function mutations at the 775-980 carboxy-terminal tail of Nha1 has
      revealed a number of residues required for function in cell cycle, most of them
      clustering in two regions, from residues 869 to 876 (cluster A) and 918 to 927
      (cluster B). The later is rather conserved in other related antiporters, while
      the former is not.

PMID- 12804784
TI  - Differential signaling through NFkappaB does not ameliorate skeletal myoblast
      apoptosis during differentiation.
AB  - During 23A2 skeletal myoblast differentiation, roughly 30% of the population
      undergoes apoptosis. Further, constitutive signaling by G12V:H-Ras or Raf:CAAX
      abrogates this apoptosis. In this study, we demonstrate an increase in NFkappaB
      activity in myoblasts that have survived and are expressing muscle-specific
      genes. NFkappaB activity is also elevated in myoblasts expressing constitutively
      active G12V:H-Ras but not Raf:CAAX. Expression of a dominant negative IkappaB
      (IkappaB-SR) sufficient to eliminate this elevated level of NFkappaB activity, in
      either the 23A2 myoblasts or their G12V:H-Ras-expressing counterparts, however,
      does not affect survival. Furthermore, expression of a constitutively active
      IkappaB kinase in 23A2 myoblasts does not protect these cells from the apoptosis
      associated with differentiation. Since signaling by IkappaB kinase can abrogate
      differentiation, this result demonstrates that abrogated differentiation and
      abrogated apoptosis are separable phenotypes.

PMID- 12804785
TI  - Mutational analysis of the Mycobacterium tuberculosis Rv1625c adenylyl cyclase:
      residues that confer nucleotide specificity contribute to dimerization.
AB  - The mycobacterial Rv1625c gene product is an adenylyl cyclase with sequence
      similarity to the mammalian enzymes. The catalytic domain of the enzyme forms a
      homodimer and residues specifying adenosine triphosphate (ATP) specificity lie at
      the dimer interface. Mutation of these residues to those present in guanylyl
      cyclases failed to convert the enzyme to a guanylyl cyclase, but dramatically
      reduced its adenylyl cyclase activity and altered its oligomeric state.
      Computational modeling revealed subtle differences in the dimer interface that
      could explain the biochemical data, suggesting that the structural and catalytic
      features of this homodimeric adenylyl cyclase are in contrast to those of the
      heterodimeric mammalian enzymes.

PMID- 12804787
TI  - A new approach to spike sorting for multi-neuronal activities recorded with a
      tetrode--how ICA can be practical.
AB  - Multi-neuronal recording with a tetrode is a powerful technique to reveal
      neuronal interactions in local circuits. However, it is difficult to detect
      precise spike timings among closely neighboring neurons because the spike
      waveforms of individual neurons overlap on the electrode when more than two
      neurons fire simultaneously. In addition, the spike waveforms of single neurons,
      especially in the presence of complex spikes, are often non-stationary. These
      problems limit the ability of ordinary spike sorting to sort multi-neuronal
      activities recorded using tetrodes into their single-neuron components. Though
      sorting with independent component analysis (ICA) can solve these problems, it
      has one serious limitation that the number of separated neurons must be less than
      the number of electrodes. Using a combination of ICA and the efficiency of
      ordinary spike sorting technique (k-means clustering), we developed an automatic
      procedure to solve the spike-overlapping and the non-stationarity problems with
      no limitation on the number of separated neurons. The results for the procedure
      applied to real multi-neuronal data demonstrated that some outliers which may be
      assigned to distinct clusters if ordinary spike-sorting methods were used can be
      identified as overlapping spikes, and that there are functional connections
      between a putative pyramidal neuron and its putative dendrite. These findings
      suggest that the combination of ICA and k-means clustering can provide insights
      into the precise nature of functional circuits among neurons, i.e. cell
      assemblies.

PMID- 12804788
TI  - Sentence processing is uniquely human.
AB  - In this article, we will focus on three fundamental issues concerning language
      processing in the human brain, and update recent advances made by functional
      neuroimaging and magnetic stimulation studies of language. First, we will provide
      the first experimental evidence that the neural basis of sentence comprehension
      is indeed specialized. Specifically, our recent functional magnetic resonance
      imaging (fMRI) study has clarified that the human left prefrontal cortex (PFC) is
      more specialized in the syntactic processes of sentence comprehension than other
      domain-general processes such as short-term memory. Second, the distinction
      between explicit and implicit syntactic processes will be clarified, based on our
      fMRI studies that elucidate syntactic specialization in the left PFC. Third, we
      will advance a hypothesis stating that distinct subregions of the left PFC are
      recruited for the syntactic integration of lexico-semantic information. The
      current direction of research in the neuroscience of language is beginning to
      reveal the uniqueness of the human mind.

PMID- 12804789
TI  - Magneto-encephalographic measurement of neural activity during period of vertigo
      induced by cold caloric stimulation.
AB  - The aim of this study was to investigate neural activity during period of
      vertiginous sensation, induced by caloric stimulation. After caloric vestibular
      stimulation (CVS) by cold water of five volunteers (n=5, age: 30+/-10), auditory
      evoked magnetic fields (AEFs) during the subsequent period of vertiginous
      sensations were measured by magnetoencephalography (MEG). Current-arrow maps
      (CAMs) were produced to estimate the spatial current distribution of the AEF
      responses, and a rotation value (dI(rot)) was calculated from the CAM. The worth
      of the dI(rot) values as indicators of vertigo was evaluated by comparing them
      with earlier reported values for elderly control (n=11, age: 67+/-5) and chronic
      dizziness (CD) (n=27, age: 68+/-8) groups (obtained from AEF responses with no
      the CVS). Although all volunteers felt vertigo during the AEF measurements, the
      AEF waveforms and CAM pattern only showed slight changes. While the dI(rot)
      values (1.43+/-0.73) just after CVS were not significantly different from those
      (1.59+/-0.46) for the elderly controls, they were significantly different from
      those (3.54+/-1.34) for the CD patients. These findings suggest that (i) the new
      parameter (dI(rot)) is more sensitively indicates dizziness (non-rotatory
      sensation) than vertigo (ii) the auditory cortical region may play an important
      role in body-balance perception of floating sensations.

PMID- 12804790
TI  - Neurodegeneration of substantia nigra accompanied with macrophage/microglia
      infiltration after intrastriatal hemorrhage.
AB  - Intrastriatal hemorrhage in rats causes neurodegenaration of the substantia nigra
      (SN) followed by the appearance of ED1(+) cells (macrophage/microglia). ED1(+)
      cells were observed for at least 8 weeks after hemorrhage. Phosphorylation of p38
      mitogen-activated protein kinase (MAPK) was shown in ED1(+) cells with the
      expression of both brain-derived neurotrophic factor (BDNF) mRNA and BDNF,
      suggesting that activated-p38 MAPK(+)/ED1(+) cells would produce BDNF and may
      exhibit trophic effect on the degenerating neurons in the SN. However, in ELISA,
      BDNF protein decreased significantly in ipsilateral SN at 7 days after
      hemorrhage, which may be due to a dramatic decrease of BDNF immunoreactive
      neurons in pars compacta. Data suggest that activation of p38 MAPK in ED1(+)
      cells infiltrating in ipsilateral SN after hemorrhage may produce BDNF, but that
      the amount of BDNF produced from ED1(+) cells is insufficient for the rescue of
      degenerating neurons.

PMID- 12804791
TI  - A decrease in interleukin-1 receptor antagonist expression in the prefrontal
      cortex of schizophrenic patients.
AB  - Interleukin-1 (IL-1) mediates psychological stress responses by regulating
      monoamine metabolism and secretion of corticotropin-releasing factor, and is
      therefore, implicated in various psychiatric diseases. To evaluate the
      contribution of IL-1 signaling to the brain pathology of schizophrenia, we
      measured protein and/or mRNA levels for IL-1beta and endogenous IL-1 receptor
      antagonist (IL-1RA) in the postmortem brain tissues of prefrontal and parietal
      cortex, putamen, and hypothalamus. Both protein and mRNA levels of IL-1RA were
      specifically decreased in the prefrontal cortex of schizophrenic patients,
      whereas IL-1beta levels were not significantly altered in all the regions
      examined. The IL-1RA decrease was not correlated with the dose of antipsychotics
      given to patients. There was no influence of this illness on protein levels for
      IL-1 receptor type 1 in the prefrontal cortex, either. In contrast, IL-1RA serum
      levels were increased in schizophrenic patients, especially in drug-free
      patients, as reported previously. These findings suggest that chronic
      schizophrenia down-regulates IL-1RA production the prefrontal cortex,
      irrespective of its impact on the periphery. IL-1RA reduction might reflect an
      immunopathologic trait of the prefrontal region in schizophrenic patients.

PMID- 12804792
TI  - Delayed neuronal damage related to microglia proliferation after mild spinal cord
      compression injury.
AB  - In order to investigate the mechanism of delayed progressive or secondary
      neuronal damage after the spinal cord injury, we developed a mild-compression
      injury model in the rat thoracic spinal cord. Our compression device consists of
      a soft silicone point of contact to the dura, in order to prevent violent injury
      that may cause axonal tears or hemorrhages in the spinal cord. Since rats often
      assume a 'standing' posture, i.e. raising head with lifting their fore-limbs,
      damage to the thoracic spinal cord was evaluated by measuring the frequency of
      'standing', which effectively indicates hind limb function. Twenty-four hours
      after compression by a 20 g weight for 10 or 20 min, the standing frequency of
      the injured rat was almost the same as that of sham animals that underwent
      laminectomy without compression. However, the standing frequency decreased with
      time; the frequency of standing at 72 h was approximately 30-50% that of sham
      animals. In the compressed spinal cord tissue, microglial cells, detected by
      lectin staining, proliferated with time. An enormous amount of microglia was
      observed at 48 and 72 h after compression, although only a small amount of cells
      were positive to lectin staining at 24 h after the compression. These results
      suggest that our mild-compression spinal cord injury model showed late-onset or
      delayed neuronal damage that may be related to pathological microglia
      proliferation.

PMID- 12804793
TI  - Acquisition and contextual switching of multiple internal models for different
      viscous force fields.
AB  - Humans can learn an enormous number of motor behaviors in different environments.
      To explain this, the MOSAIC model proposes that multiple internal models are
      acquired in the brain, which can be switched. However, previous behavioral
      studies that examined arm-movement adaptations to multiple environments reported
      a rather limited learning capability. Hitherto, humans have been believed
      incapable of learning two opposite viscous force fields, which are both dynamic
      transformations and depend on the same state variable, presented in a random
      order with only a visual cue. In contrast, this study found that humans are
      capable of this. Elbow joint movements to specified targets were perturbed by
      either resistive or assistive viscous force fields generated by a single degree
      of-freedom manipulandum. The resistive or assistive viscous force fields were
      cued by a blue or red color on a CRT screen, respectively. The squared distance
      between the end point and the target, and the variance of the joint angular
      velocities were used as kinematic performance indices. These movement errors
      decreased significantly as a function of the training days. Aftereffects and
      learning consolidation were demonstrated in the random presentation of the two
      force fields. Consequently, humans were able to learn the multiple and distinct
      internal models of the two force fields and appropriately switch them even for a
      random presentation cued only by color after several days of training. This study
      suggests that none of the previously proposed conditions for multiple internal
      model learning are necessary prerequisites, and indicates that the difficulty in
      learning is determined by the balance between the effectiveness of contextual
      information and the similarity of force fields.

PMID- 12804794
TI  - Effects of lactate/pyruvate on synaptic plasticity in the hippocampal dentate
      gyrus.
AB  - The present study was undertaken to investigate whether monocarboxylates (lactate
      and pyruvate) can support synaptic plasticity. As an index of synaptic activity,
      population spikes (PS) were recorded in the hippocampal dentate gyrus.
      Replacement of glucose with monocarboxylates maintained PS after transient
      depression, and supported a similar degree of paired-pulse facilitation (PPF).
      Monocarboxylates-supported long-term potentiation (LTP), but the degree of
      enhancement was less than that of glucose-supported PS. Monocarboxylates failed
      to support long-term depression (LTD). These results indicate that
      monocarboxylates could serve as sufficient substrates for PPF, and that they
      could also support LTP but with less efficiency than glucose.

PMID- 12804795
TI  - Neonatal hypoxia-ischemia reduces ganglioside, phospholipid and cholesterol
      contents in the rat hippocampus.
AB  - Hypoxia-ischemia is a common cause of neonatal brain damage producing serious
      impact on cerebral maturation. This report demonstrates that rats submitted to
      hypoxia-ischemia present a marked decrease in hippocampal gangliosides,
      phospholipids and cholesterol contents as from 7 days after the injury. Although
      chromatographic profiles of the different ganglioside species (GM1, GD1a, GD1b,
      and GT1b) from the hippocampus of hypoxic-ischemic hippocampi groups (HI) were
      apparently unaffected, as compared with controls, there were quantitative
      absolute reductions in HI. The phospholipid patterns were altered in HI as from
      the 14th to the 30th day after the injury, where phosphatidylcholine (PC)
      quantities were higher than phosphatidylethanolamine (PE); additionally, the
      cardiolipin band was detected only in hippocampi of control adult rats. In
      general, the absolute quantities of phospholipids were lower in HI than in
      correspondent controls since 7th day after the injury. Considering that reported
      effects were maintained, we suggest they express a late biochemical response
      triggered by the neonatal hypoxic-ischemic episode; the consequences would be
      cell death and a delay on brain development, expressed by a reduction on
      synaptogenesis and myelinogenesis processes.

PMID- 12804796
TI  - N-methylated beta-carbolines protect PC12 cells from cytotoxic effect of MPP+ by
      attenuation of mitochondrial membrane permeability change.
AB  - Opening of the mitochondrial permeability transition pore has been recognized to
      be involved in cell death. The present study investigated the effect of beta
      carbolines (harmaline and harmalol) on the MPP(+)-induced change in the
      mitochondrial membrane permeability and cell death in differentiated PC12 cells.
      beta-Carbolines and antioxidants (superoxide dismutase, catalase, ascorbate or
      rutin) prevented the loss of cell viability in PC12 cells treated with 250 microM
      MPP(+), while the effects of N-acetylcysteine and dithiothreitol were not
      observed. beta-Carbolines reduced the condensation and fragmentation of nuclei
      caused by MPP(+) in PC12 cells. beta-Carbolines alone did not exhibit a
      significant cytotoxic effect on PC12 cells. beta-Carbolines (50 microM) inhibited
      the decrease in mitochondrial transmembrane potential, cytochrome c release,
      activation of caspase-3, formation of reactive oxygen species (ROS) and depletion
      of GSH caused by MPP(+) in PC12 cells. beta-Carbolines reduced the hydrogen
      peroxide- or SIN-1-induced cell death in PC12 cells. The results suggest that
      beta-carbolines may attenuate the MPP(+)-induced viability loss in PC12 cells by
      inhibition of change in the mitochondrial membrane permeability and by
      antioxidant effect.

PMID- 12804797
TI  - Changes in cerebellar fastigial burst activity related to saccadic gain
      adaptation in the monkey.
AB  - The accuracy of saccades is ensured by an adaptive mechanism that probably
      involves the cerebellum. We examined the discharge of saccade-related neurons in
      the fastigial oculomotor region (FOR) during adaptation. Using a conventional
      intrasaccadic step paradigm, we changed the gain of saccades elicited by a 10
      degrees horizontal target step to the side of unit recording. As a measure of
      neural activity, we took the number of spikes occurring in a 30 or 40 ms time
      window starting at 30 ms before saccade onset, which corresponded roughly to the
      foot and rising phase of the burst. A gain decrease was accompanied by a
      significant increase in spike discharge (6/6), and a gain increase by a
      significant reduction in discharge (3/3). During the course of adaptation, the
      neural activity and gain exhibited changes with a similar course but in the
      opposite direction. Regression analysis indicated that the two variables were
      significantly correlated (7/8). The present study has shown that activity of FOR
      neurons is altered during adaptive modification of saccade size. Our data are
      consistent with the hypothesized suppressive action of the FOR on ipsiversive
      saccades and provide support on a single-neuron basis for the cerebellar
      involvement in short-term saccade adaptation.

PMID- 12804798
TI  - Transection of intrinsic polysynaptic pathways reduces N-methyl-D-aspartate
      neurotoxicity in hippocampal slice cultures.
AB  - Hippocampal CA1 neurons have been shown to be highly susceptible to
      excitotoxicity produced by various forms of insult. CA1 neurotoxicity is partly
      dependent on over activity of N-methyl-D-aspartate (NMDA) receptors. It is
      unclear, however, if sensitivity of this region to excitotoxicity is related to
      inherent properties of CA1 neurons and/or network activation of polysynaptic
      pathways. The present studies examined the role of mossy fiber and Schaffer
      collateral function in promoting NMDA-induced neurodegeneration. Organotypic
      hippocampal cultures were subjected to transection of mossy fibers, Schaffer
      collaterals, or CA1 efferent fibers and then exposed to NMDA (20 microM) for 1 h.
      Hippocampal damage was assessed 24 h later via fluorescent microscopy. NMDA
      exposure produced significant excitotoxicity in all regions (160-500% of
      control), particularly in the CA1. In each region, toxicity was reduced by co
      exposure to NMDA with MK-801 (20 microM), to near-control levels. Surgical
      transection of mossy fibers and Schaffer collaterals significantly reduced NMDA
      induced neurotoxicity in the CA1 ( approximately 20%), and to a lesser extent,
      the CA3 and dentate regions. Conversely, transection of CA1 efferent fibers did
      not reduce the neurotoxicity in these regions. These data indicate that CA1
      neurotoxicity caused by excitotoxic insult depends, in part, on 'network
      activation' of intrinsic polysynaptic pathways.

PMID- 12804799
TI  - Blast-induced neurotrauma in whales.
AB  - A majority of investigations on primary blast injuries have focused on gas
      containing organs, while the likelihood of blast-induced neurotrauma remains
      underrated. In Norway minke whales (Balaenoptera acutorostrata) are hunted using
      small fishing boats rigged with harpoon guns, which fire harpoons tipped with a
      grenade containing a charge of 30-g penthrite. The grenade detonates 60-70 cm
      inside the animal. The present study was undertaken to characterize the
      neuropathological changes caused by the penthrite blast and evaluate its role in
      the loss of consciousness and death in hunted whales. The study included 37 minke
      whales that were examined shipboard. The brains were later subjected to gross and
      light microscopy examination. The results showed that intra-body detonation of
      the grenade in near vicinity of the brain resulted in trauma similar to severe
      traumatic brain injury associated with a direct blow to the head. Detonation in
      more distant areas of the body resulted in injuries resembling acceleration
      induced diffuse traumatic brain injury. The authors conclude that even if several
      vital organs were fatally injured in most whales, the neurotrauma induced by the
      blast-generated pressure waves were the primary cause for the immediate or very
      rapid loss of consciousness and death.

PMID- 12804801
TI  - Resuscitation greats: Marshall Hall and his ready method of resuscitation.

PMID- 12804802
TI  - Simplified meta-analysis of clinical trials in resuscitation.
AB  - OBJECTIVE: To present and demonstrate a new simplified method for synthesizing
      results of multiple clinical trials in resuscitation research. METHODS: The mean
      difference across studies in the proportion of favorable outcomes between
      experimental and control groups is calculated. This difference is shown to have a
      t-distribution. Its significance can be ascertained with a simple t-test. The
      analysis can be implemented in a one-page computer spreadsheet. RESULTS:
      Simplified meta-analysis provides high sensitivity and can be extended to include
      weighting of studies according to size or quality, comparison of subgroups of
      studies, tests for outliers, and calculation of the power of the meta-analysis.
      Sample analyses are presented for two experimental forms of cardiopulmonary
      resuscitation (CPR): interposed abdominal compression (IAC) CPR and active
      compression-decompression (ACD) CPR. CONCLUSIONS: Traditional narrative reviews,
      taking note of the proportion of individual studies with statistically
      significant results, can lead to erroneous conclusions and unnecessary delays in
      the clinical use of research findings. Simplified meta-analysis can provide
      rapid, quantitative, and accurate estimates of the amount of benefit or harm from
      an experimental intervention and can further empower physicians to practice
      evidence-based medicine.

PMID- 12804803
TI  - CPR training in households of patients with chest pain.
AB  - The objectives of this study are to (1). quantify prior cardiopulmonary
      resuscitation (CPR) training in households of patients presenting to the
      Emergency Department (ED) with or without chest pain or ischaemic heart disease
      (IHD); (2). evaluate the willingness of household members to undertake CPR
      training; and (3). identify potential barriers to the learning and provision of
      bystander CPR. A cross-sectional study was conducted by surveying patients
      presenting to the ED of a metropolitan teaching hospital over a 6-month period.
      Two in five households of patients presenting with chest pain or IHD had prior
      training in CPR. This was no higher than for households of patients presenting
      without chest pain or IHD. Just under two in three households of patients
      presenting with chest pain or IHD were willing to participate in future CPR
      classes. Potential barriers to learning CPR included lack of information on CPR
      classes, perceived lack of intellectual and/or physical capability to learn CPR
      and concern about causing anxiety in the person at risk of cardiac arrest.
      Potential barriers to CPR provision included an unknown cardiac arrest victim and
      fear of infection. The ED provides an opportunity for increasing family and
      community capacity for bystander intervention through referral to appropriate
      training.

PMID- 12804804
TI  - Artificial ventilation for basic life support leads to hyperventilation in first
      aid providers.
AB  - The 'Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care - International Consensus on Science' recommend an artificial
      ventilation volume of 10 ml/kg bodyweight (equivalent to a tidal volume of 700
      1000 ml) without the use of supplemental oxygen in adults with respiratory
      arrest. For first aid providers using the mouth-to-mouth or mouth-to-nose
      ventilation technique, respectively, a ventilation volume of approximately 9.6
      l/min results. Additionally, a deep breath is recommended before each ventilation
      to increase the end-expiratory oxygen concentration of the air exhaled by the
      first aid provider. To investigate the effects of these recommendations in
      healthy volunteers, test persons were asked to ventilate an artificial lung model
      for a period of up to 10 min. The tidal volume was set at 800 ml at a breathing
      rate of 12/min. End-tidal carbon dioxide, oxygen saturation (measured by pulse
      oximetry), and heart rate were measured continuously. Capillary blood gas samples
      were collected and non-invasive blood pressure readings were recorded prior to
      the start of ventilation and immediately after the end of the measuring period.
      The data reveal a statistically significant and clinically relevant decrease in
      end-tidal carbon dioxide pressure (P<0.001, median decrease 14 mmHg), and the
      occurrence of hyperventilation-associated symptoms such as paraesthesia,
      dizziness, and carpopedal spasms in more than 75% of the participants. Clinically
      and statistically significant hyperventilation results in first aid providers
      performing artificial ventilation according to the guidelines. This artificial
      ventilation is associated with a significant decrease in capillary and end-tidal
      carbon dioxide pressure as well as with multiple symptoms of an acute
      hyperventilation syndrome. Ventilation performed according to these guidelines
      may cause injury to the health of the first aid provider. Rescuers ventilating
      the victim should be replaced at regular intervals and the recommendation to take
      a deep breath before each ventilation should not be upheld in order to minimise
      the risk of hyperventilation.

PMID- 12804805
TI  - Reverse CPR: a pilot study of CPR in the prone position.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR), as described in 1960, remains
      the cornerstone of therapy for cardiopulmonary arrest. Recent case reports have
      described CPR in the prone position. We hypothesized rhythmic back pressure on a
      patient in the prone position with sternal counter-pressure (termed reverse CPR
      here) would increase intra-thoracic pressure and in turn systolic blood pressure
      (SBP) during cardiac arrest versus standard CPR. METHODS AND RESULTS: Six
      patients from Columbia Presbyterian Medical Center's Cardiac and Medical
      Intensive Care Units (CICU and MICU) were enrolled. Eligible patients had
      suffered circulatory arrest and failed standard CPR for at least 30 min. After
      enrollment the patients received 15 additional min of standard CPR and then
      reverse CPR for 15 min. The study's primary endpoint, mean SBP, significantly
      improved from 48 mmHg during standard CPR to 72 mmHg during reverse CPR (mean
      improvement=23+/-14 mmHg). Mean calculated mean arterial pressure (MAP) was also
      improved significantly from 32 mmHg during standard CPR to 46 mmHg during reverse
      CPR (mean improvement=14+/-11 mmHg). The mean diastolic blood pressure (DBP)
      improved from 24 mmHg during standard to 34 mmHg during reverse CPR (mean
      improvement=10+/-12 mmHg). This difference did not meet statistical significance.
      No patients had return of spontaneous circulation. CONCLUSIONS: Reverse CPR
      generates higher mean SBP and higher mean MAP during circulatory arrest than
      standard CPR. These novel findings justify further research into this technique.

PMID- 12804806
TI  - Cardiac arrest: long-term cognitive and imaging analysis.
AB  - BACKGROUND: Neurological and cognitive sequelae resulting from cardiac arrest
      (CA), despite their potential personal and social impact, are usually not
      considered as major outcome measures in long-term analysis of survivors. The aim
      of this study is to analyze the contribution of neuropsychological testing and
      cerebral imaging to the development of a long-term classification of neurological
      impairment. PATIENTS AND METHODS: A total of 19 patients admitted over a 3 years
      period in an eight-bed intensive care unit of a tertiary care hospital with a
      diagnosis of CA were alive and attended a 6-month follow-up consultation. Eleven
      of these patients agreed to participate in this study carried out between 1 and 3
      years after CA. Patients were classified using the Cerebral Performance
      Categories (CPC), neurological examination, detailed cognitive testing and
      computerized tomography (CT) scan with qualitative and quantitative imaging
      analysis. RESULTS: Six of the 11 patients had good cerebral performance. Verbal
      and visuo-spatial short-term memory scores were associated with CPC. All patients
      with at least moderate cerebral disability had abnormal verbal memory test
      results compared with only one survivor with CPC 1; visuo-spatial short-term
      memory was abnormal in four moderately affected survivors and normal in those
      with CPC 1. The bicaudate ratio evaluated in the CT scan was correlated with the
      verbal memory score while the III ventricle diameter correlated with the
      executive functions score, suggesting involvement of different brain areas in
      these functions. CONCLUSIONS: Neuropsychological and CT scan measurements are
      proxy measures of long-term impairment of CA survivors, providing a dichotomized
      global evaluation of CA survivors in close agreement with CPC.

PMID- 12804807
TI  - Increased cortical cerebral blood flow by continuous infusion of adrenaline
      (epinephrine) during experimental cardiopulmonary resuscitation.
AB  - OBJECTIVE: To study the effects of continuously administered adrenaline
      (epinephrine), compared to bolus doses, on the dynamics of cortical cerebral
      blood flow during experimental cardiopulmonary resuscitation (CPR), and after
      restoration of spontaneous circulation (ROSC). METHODS: Ventricular fibrillation
      was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval,
      closed-chest CPR was started. The animals were randomised into two groups. One
      group received three boluses of adrenaline (20 microg/kg) at 3-min intervals. The
      other group received an initial bolus of adrenaline (20 microg/kg) followed by an
      infusion of adrenaline (10 microg/kg x min). After 9 min of CPR, defibrillation
      was attempted, and if spontaneous circulation was achieved the adrenaline
      infusion was stopped. Cortical cerebral blood flow was measured continuously
      using Laser-Doppler flowmetry. Jugular bulb oxygen saturation was measured to
      reflect global cerebral oxygenation. Repeated measurements of 8-iso-prostaglandin
      F(2alpha) (8-iso-PGF(2alpha)) in jugular bulb plasma were performed to evaluate
      cerebral oxidative injury. RESULTS: During CPR mean cortical cerebral blood flow
      was significantly higher (P=0.009) with a continuous adrenaline infusion than
      with repeated bolus doses. Following ROSC there was no significant difference in
      cortical cerebral blood flow between the two study groups. No differences in
      coronary perfusion pressure, rate of ROSC, jugular bulb oxygen saturation or 8
      iso-PGF(2alpha) were seen between the study groups. CONCLUSIONS: Continuous
      infusion of adrenaline (10 microg/kg x min) generated a more sustained increase
      in cortical cerebral blood flow during CPR as compared to intermittent bolus
      doses (20 microg/kg every third minute). Thus, continuous infusion might be a
      more appropriate way to administer adrenaline as compared to bolus doses during
      CPR.

PMID- 12804808
TI  - Cardiopulmonary resuscitation following minimally invasive repair of pectus
      excavatum (Nuss technique).

PMID- 12804809
TI  - Medical end-of-life decisions in Norway.

PMID- 12804810
TI  - Transient right bundle branch block unmasking anterior myocardial infarction.

PMID- 12804811
TI  - Fever-induced ST-segment elevation and T-wave alternans in a patient with Brugada
      syndrome.

PMID- 12804812
TI  - Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular
      fibrillation cardiac arrest in pigs.

PMID- 12804813
TI  - The "what" and "where" of object representations in infancy.
AB  - Four-month-olds' memory for surface feature and location information was tested
      following brief occlusions. When the target objects were images of female faces
      or monochromatic asterisks infants showed increased looking times following a
      change in identity or color but not following a change in location or
      combinations of feature and location information. When the target objects were
      images of manipulable toys, the infants showed increased looking times following
      a change in location but not identity or the binding of location and identity
      information. This evidence is consistent with the idea that young infants are
      unable to maintain the information processed separately in both the dorsal and
      ventral visual streams during occlusions. Our results suggest that it is the
      target's affordance for action that determines whether the dorsal or ventral
      information is selectively maintained during occlusion.

PMID- 12804814
TI  - Perseverative responding in a violation-of-expectation task in 6.5-month-old
      infants.
AB  - In the present research, 6.5-month-old infants perseverated in a violation-of
      expectation task designed to examine their reasoning about width information in
      containment events. After watching a familiarization event in which a ball was
      lowered into a wide container, the infants failed to detect the violation in a
      test event in which the same ball was lowered into a container only half as wide
      as the ball (narrow-container test event). This negative result (which was
      replicated in another experiment) was interpreted in terms of a recent problem
      solving account of infants' perseverative errors in various means-end tasks
      (Aguiar, A., & Baillargeon, R. (2000). Perseveration and problem solving in
      infancy. In H. W. Reese (Ed.), Advances in child development and behavior (Vol.
      27, pp. 135-180). San Diego, CA: Academic Press). It was assumed that the infants
      in the present experiments (1) did not attend to the relative widths of the ball
      and container in their initial analysis of the narrow-container test event, (2)
      categorized the event as similar to the familiarization event shown on the
      preceding trials, and (3) retrieved the expectation they had formed for that
      event ("the ball will fit into the container"), resulting in a perseverative
      error. This interpretation was supported by additional experiments in which
      different modifications were introduced that led to non-perseverative responding,
      indicating that 6.5-month-old infants could detect the violation in the narrow
      container test event. The present findings are important for several reasons.
      First, they provide the first demonstration of perseverative responding in a
      violation-of-expectation task. Second, they make clear the breadth and usefulness
      of the problem-solving account mentioned above. Finally, they add to the evidence
      for some degree of continuity between infants' and adults' problem-solving
      abilities.

PMID- 12804815
TI  - What paradox? A response to Naigles (2002).

PMID- 12804817
TI  - The SNARC effect: an instance of the Simon effect?
AB  - Our aim was to investigate the relations between the Spatial-Numerical
      Association of Response Codes (SNARC) effect and the Simon effect. In Experiment
      1 participants were required to make a parity judgment to numbers from 1 to 9
      (without 5), by pressing a left or a right key. The numbers were presented to
      either the left or right side of fixation. Results showed the Simon effect (left
      side stimuli were responded to faster with the left hand than with the right hand
      whereas right-side stimuli were responded to faster with the right hand), and the
      SNARC effect (smaller numbers were responded to faster with the left hand than
      with the right hand, whereas larger numbers were responded to faster with the
      right hand). No interaction was found between the Simon and SNARC effects,
      suggesting that they combine additively. In Experiment 2 the temporal distance
      between formation of the task-relevant non-spatial stimulus code and the task
      irrelevant stimulus spatial code was increased. As in Experiment 1, results
      showed the presence of the Simon and SNARC effects but no interaction between
      them. Moreover, we found a regular Simon effect for faster RTs, and a reversed
      Simon effect for longer RTs. In contrast, the SNARC effect did not vary as a
      function of RT. Taken together, the results of the two experiments show that the
      SNARC effect does not simply constitute a variant of the Simon effect. This is
      considered to be evidence that number representation and space representation
      rest on different neural (likely parietal) circuits.

PMID- 12804818
TI  - Representing others' actions: just like one's own?
AB  - Previous research has shown that observing others' actions can affect individual
      performance of the same actions. In the present study, we developed a new
      paradigm to investigate whether and how complementary actions at the disposal of
      another agent are represented and influence one's own actions. A spatial
      compatibility task was distributed among two people so that each participant took
      care of one of two responses. The identical task was performed alone and
      alongside another participant. There was a spatial compatibility effect in the
      group setting only. It was similar to the effect obtained when one person took
      care of both responses. This result suggests that one's own actions and others'
      actions are represented in a functionally equivalent way.

PMID- 12804820
TI  - Inhibitory priming effects in auditory word recognition: when the target's
      competitors conflict with the prime word.
AB  - Several studies indicate that the number of similar sounding words that are
      activated during recognition is a powerful predictor of performance on auditory
      targets. Words with few competitors are processed more quickly and accurately
      than words with many competitors. In the present study, we examined the
      contribution of the competitor set size in determining the magnitude of the
      inhibitory priming effect. The data show that the priming effect is stronger when
      word targets have few competitors. This result supports the view of direct
      competition between lexical candidates.

PMID- 12804819
TI  - Reasoning about a hidden object after a delay: evidence for robust
      representations in 5-month-old infants.
AB  - The present research examined two alternative interpretations of violation-of
      expectation findings that young infants can represent hidden objects. One
      interpretation is that, when watching an event in which an object becomes hidden
      behind another object, infants form a prediction about the event's outcome while
      both objects are still visible, and then check whether this prediction was
      accurate. The other interpretation is that infants' initial representations of
      hidden objects are weak and short-lived and as such sufficient for success in
      most violation-of-expectation tasks (as objects are typically hidden for only a
      few seconds at a time), but not more challenging tasks. Five-month-old infants
      succeeded in reasoning about the interaction of a visible and a hidden object
      even though (1) the two objects were never simultaneously visible, and (2) a 3-
      or 4-min delay preceded the test trials. These results provide evidence for
      robust representations of hidden objects in young infants.

PMID- 12804821
TI  - Native plants as bioindicators of air pollutants: contributed papers to a
      symposium held in conjunction with the 34th air pollution workshop.

PMID- 12804822
TI  - Native plant species suitable as bioindicators and biomonitors for airborne
      fluoride.
AB  - For 30-40 years airborne fluoride, usually in the form of HF or SiF4, was one of
      the most important and damaging air pollutants affecting forests, crops and
      natural vegetation. It is much more toxic than most other air pollutants such as
      O3 or SO2 because injury to the most sensitive species begins when they are
      exposed to a concentration below 1 ppb (ca. 0.8 microg m(-3)) for a 1- to 3-day
      period. The long-term threshold concentration is around 0.25-0.30 microg m(-3).
      Higher concentrations and longer durations of exposure induce much more rapid and
      extensive injury. However, there is a difference in sensitivity between the most
      and least sensitive species of around 2-3 orders of magnitude and most species
      possess a degree of resistance. Dramatic improvements in engineering technology
      have greatly reduced emissions but because of the high toxicity, cases of
      vegetation injury are still common, even in developed countries, and cases
      involving litigation still occur. Therefore there is a continuing need for
      bioindicators and biomonitoring of fluorides, so this paper reviews the subject,
      drawing attention to the strengths and limitations of the techniques. Visible
      symptoms are described and illustrated and tables of relative sensitivity are
      given and their limitations discussed. Finally, examples of biomonitoring in
      Europe and the USA are presented.

PMID- 12804823
TI  - Monitoring the impact of sulphur with the Austrian Bioindicator Grid.
AB  - In Austria, the impact of sulphur has been assessed since 1985 with the help of
      the Austrian Bioindicator Grid on 760 sample plots with Picea abies as the main
      tree species (90%). The annual sampling allows a precise evaluation of the
      temporal and regional development of the impact of sulphur on the basis of legal
      standards. Despite the reduction of SO2 emissions in Austria, the legal standard
      is still exceeded on 8% of the plots. These plots are mainly located near large
      Austrian emittors, but also in areas affected by transboundary sulphur emissions
      from neighbouring countries. The present paper describes how the Bioindicator
      Grid can be applied for the control of legal requirements to enact effective
      clean air measures in Austria and take supportive measures that reduce the impact
      of sulphur from emittors in neighbouring countries.

PMID- 12804824
TI  - Historical and current atmospheric deposition to the epilithic lichen
      Xanthoparmelia in Maricopa County, Arizona.
AB  - Spatial patterns of atmospheric deposition of trace elements to an epilithic
      lichen were assessed using a spatial grid of 28 field sites in 1998 throughout
      Maricopa County, Arizona, USA. In addition, samples of Xanthoparmelia spp. from
      Arizona State University lichen herbarium material (1975-1976) was utilized for a
      limited number of sites in order to explore temporal trends. The lichen material
      was cleaned, wet digested and analyzed by ICP-MS for a suite of elemental
      concentrations [antimony (Sb), cadmium (Cd), cerium (Ce), chromium (Cr), cobalt
      (Co), copper (Cu), dysprosium (Dy), europium (Eu), gadolinium (Gd), gold (Au),
      holmium (Ho), lead (Pb), lutetium (Lu), neodymium (Nd), nickel (Ni), palladium
      (Pd), platinum (Pt), praseodymium (Pr), samarium (Sm), scandium (Sc), silver
      (Ag), terbium (Tb), thulium (Tm), tin (Sn), uranium (U), ytterbium (Yb), yttrium
      (Y), and zinc (Zn)]. Cluster analysis and principal component analysis suggest
      three major factors, which, depending on regional aerosol fractionation, explain
      most of the variation in elemental signatures: (1) a group of widely distributed
      rare earth elements (2) a highly homogenous Co, Cr, Ni, and Sc component
      representing the influence of mafic rocks, and (3) anthropogenic emissions.
      Elemental concentrations in Maricopa County lichens were generally comparable to
      those reported for relatively unpolluted areas. Only highly urbanized regions,
      such as the greater Phoenix Metropolitan Area and the NW corner of the county,
      exhibited elevated concentrations for Zn, Cu, Pb, and Cd. Lead levels in lichens
      have fallen over the last 30 years by 71%, while Zn concentrations for some
      regions have increased by as much as 245%. From the spatial pattern of elemental
      deposition for Cd, Cu, Ni, Pr, Pb, and Cu, we infer that agriculture, mining,
      industrial activities, and traffic probably are the major air pollutant sources
      in Maricopa County.

PMID- 12804825
TI  - Response of native plants of northeastern United States and southern Spain to
      ozone exposures; determining exposure/response relationships.
AB  - Tropospheric ozone has been identified as the most important regional scale air
      pollutant across much of eastern United States of America and many areas of
      Mediterranean climes in southern Europe. Recent field surveys in the northeastern
      USA and in southeastern Spain have revealed many additional plant species that
      exhibit symptoms typical of ozone-induced injuries. Objectives of this study were
      to confirm ozone as the cause of the observed foliar symptoms, determine ozone
      induced exposure/response relationships, and identify possible bio-indicator
      species. Thirteen native species of northeastern USA and 27 native species of
      southeastern Spain were selected for study. Plant species were exposed to ozone
      within 16 CSTR chambers in a greenhouse during the summer seasons of 2000 and
      2001; ozone exposures of 30, 60, 90, and 120 ppb were delivered for 7 h/day, 5
      days/week. Results have confirmed that with few exceptions, symptoms observed in
      the field were induced by exposures to ambient ozone. Species differed
      significantly in terms of the exposures required for the initiation of visible
      symptoms and subsequent injury progression.

PMID- 12804826
TI  - Ozone air pollution and foliar injury development on native plants of
      Switzerland.
AB  - The objectives of this study were to examine the foliar sensitivity to ozone
      exposure of 12 tree, shrub, and herbaceous species native to southern Switzerland
      and determine the seasonal cumulative ozone exposures required to induce visible
      foliar injury. The study was conducted from the beginning of May through the end
      of August during 2000 and 2001 using an open-top chamber research facility
      located within the Lattecaldo Cantonal Forest Nursery in Canton Ticino, southern
      Switzerland (600 m asl). Plants were examined daily and dates of initial foliar
      injury were recorded in order to determine the cumulative AOT40 ppb h ozone
      exposure required to cause visible foliar injury. Plant responses to ozone varied
      significantly among species; 11 species exhibited visible symptoms typical of
      exposures to ambient ozone. The symptomatic species (from most to least
      sensitive) were Populus nigra, Viburnum lantana, Salix alba, Crataegus monogyna,
      Viburnum opulus, Tilia platyphyllos, Cornus alba, Prunus avium, Fraxinus
      excelsior, Ribes alpinum, and Tilia cordata; Clematis spp. did not show foliar
      symptoms. Of the 11 symptomatic species, five showed initial injury below the
      critical level AOT40 10 ppmh O3 in the 2001 season.

PMID- 12804827
TI  - Ozone injury on cutleaf coneflower (Rudbeckia laciniata) and crown-beard
      (Verbesina occidentalis) in Great Smoky Mountains National Park.
AB  - Incidence and severity of visible foliar ozone injury on cutleaf coneflower
      (Rudbeckia laciniata L.) and crown-beard (Verbesina occidentalis Walt.) were
      determined along selected trails at three locations in Great Smoky Mountains
      National Park during the summers of 2000 and 2001: Clingmans Dome, Cherokee
      Orchard Road and Purchase Knob. Cutleaf coneflower exhibited a greater amount of
      foliar injury than crown-beard each year of the 2-year study. Incidence and
      severity of injury was significantly greater for cutleaf coneflower growing near
      the edge of the Clingmans Dome trail than in the interior of the stand. Injury
      was greater at Clingmans Dome than Purchase Knob (70% vs. 40% ozone-injured
      plants, respectively), coincident with greater ozone exposures. In contrast to
      Clingmans Dome, there were no differences in injury between plants growing near-
      and off-trail at Purchase Knob. Differences in sensitivity to ozone were not
      observed for crown-beard growing near the edge compared with the interior of the
      stand adjacent to the Cherokee Orchard Road Loop. Ozone injury was greatest on
      the lower leaves for both species sampled with over 95% of the injured leaves
      occurring on the lower 50% of the plant. This is the first report of foliar ozone
      injury on these plant species in situ, in the Park, illustrating the great
      variability in symptom expression with time, and within and between populations.

PMID- 12804828
TI  - Interpreting spatial variation in ozone symptoms shown by cutleaf cone flower,
      Rudbeckia laciniata L.
AB  - Visible injury caused by ozone is recorded every year in native plant species
      growing in Great Smoky Mountains National Park (USA). One of the most sensitive
      species, cutleaf coneflower (Rudbeckia laciniata L.), shows great variation in
      symptoms between and within populations but the causes of this variation and its
      ecological significance are currently unknown. This paper presents data relating
      to genetic variation, ozone concentrations, stomatal conductance and light (PAR)
      within populations. The data show that populations differ in genetic diversity,
      one consisting of only three genets while another was very diverse. In the former
      population, symptoms varied greatly within a single genet, pointing to a large
      micro-environmental influence. Measurements of ozone, stomatal conductance and
      PAR within plant canopies suggest that variation in symptom expression is
      unlikely to be due to differences in ozone flux and more likely to be due to
      variation in light. The variation in visible symptoms raises the question of what
      bioindicators actually indicate, and it suggests that symptoms should be
      interpreted with great caution until the underlying causes of that variation are
      fully understood.

PMID- 12804829
TI  - Use of bioindicators and passive sampling devices to evaluate ambient ozone
      concentrations in north central Pennsylvania.
AB  - Ambient concentrations of tropospheric ozone and ozone-induced injury to black
      cherry (Prunus serotina) and common milkweed (Asclepias syriaca) were determined
      in north central Pennsylvania from 29 May to 5 September 2000 and from 28 May to
      18 September 2001. Ogawa passive ozone samplers were utilized within openings at
      15 forested sites of which six were co-located with TECO model 49 continuous
      ozone monitors. A significant positive correlation was observed between the Ogawa
      passive samplers and the TECO model 49 continuous ozone monitors for the 2000
      (r=0.959) and 2001 (r=0.979) seasons. In addition, a significant positive
      correlation existed in 2000 and 2001 between ozone concentration and elevation
      (r=0.720) and (r=0.802), respectively. Classic ozone-induced symptoms were
      observed on black cherry and common milkweed. In 2000, initial injury was
      observed in early June, whereas for the 2001 season, initial injury was initially
      observed in late June. During both seasons, injury was noted at most sites by mid
      to late-July. Soil moisture potential was measured for the 2001 season and a
      significant positive relationship (P<0.001) showed that injury to black cherry
      was a function of cumulative ozone concentrations and available soil moisture.

PMID- 12804830
TI  - Assessment of ozone visible symptoms in the field: perspectives of quality
      control.
AB  - The second UN/ECE ICP-Forests Intercalibration Course on the Assessment of Ozone
      Injury on European Tree Species was carried out in August 2001 at Lattecaldo
      (Canton Ticino, CH) and Moggio (Lombardy, I). Forty-eight experts from several
      European countries participated in the exercises and assessed visible symptoms of
      ozone injury both in open-top chambers (OTC) (Lattecaldo) and under open field
      (Moggio) conditions. Evaluation of the results indicated a large variability
      among the teams and call for adequate training of the observers prior to symptom
      assessment for quality assurance purposes. Highest variability was found for the
      species developing unclear symptoms which could be confused with senescence
      processes; such species should not be used in the field. The authors provide
      suggestions to improve the reliability of the ozone injury assessment on forest
      plant species.

PMID- 12804831
TI  - Ozone sensitivity of Fagus sylvatica and Fraxinus excelsior young trees in
      relation to leaf structure and foliar ozone uptake.
AB  - During the summer of 2001, 2-year-old Fraxinus excelsior and Fagus sylvatica
      plants were subjected to ozone-rich environmental conditions at the Regional
      Forest Nursery at Curno (Northern Italy). Atmospheric ozone concentrations and
      stomatal conductance were measured, in order to calculate the foliar fluxes by
      means of a one-dimensional model. The foliar structure of both species was
      examined (thickness of the lamina and of the individual tissues, leaf mass per
      area, leaf density) and chlorophyll a fluorescence was determined as a response
      parameter. Stomatal conductance was always greater in Fraxinus excelsior, as was
      ozone uptake, although the highest absorption peaks did not match the peaks of
      ozone concentration in the atmosphere. The foliar structure can help explain this
      phenomenon: Fraxinus excelsior has a thicker mesophyll than Fagus sylvatica
      (indicating a greater photosynthesis potential) and a reduced foliar density.
      This last parameter, related to the apoplastic fraction, suggests a greater
      ability to disseminate the gases within the leaf as well as a greater potential
      detoxifying capacity. As foliar symptoms spread, the parameters relating to
      chlorophyll a fluorescence also change. PI (Performance Index, Strasser, A.,
      Srivastava, A., Tsimilli-Michael, M., 2000. The fluorescence transient as a tool
      to characterize and screen photosynthetic samples. In: Yunus, M., Pathre, U.,
      Mohanty, P., (Eds.) Probing Photosynthesis: Mechanisms, Regulation and
      Adaptation. Taylor & Francis, London, UK, pp. 445-483.) has proved to be a more
      suitable index than Fv/Fm (Quantum Yield Efficiency) to record the onset of
      stress conditions.

PMID- 12804832
TI  - From critical levels to critical loads for ozone: a discussion of a new
      experimental and modelling approach for establishing flux-response relationships
      for agricultural crops and native plant species.
AB  - Present critical levels for ozone (O3) for protecting vegetation against adverse
      effects are based on exposure-response relationships mainly derived from open-top
      chamber experiments and are expressed as an Accumulated exposure Over a Threshold
      of 40 ppb (AOT40). In that context with a revision of the UN (United Nations)-ECE
      (Economic Commission for Europe) Gothenburg protocol, AOT40 values should be
      replaced by flux-oriented quantities, i.e. in the end by critical loads. At
      present, the database for the derivation of critical loads for O3 is extremely
      inadequate. Furthermore, the currently available flux-response relationships are
      also derived from open-top chamber experiments. The use of a relationship for
      spring wheat in a risk assessment for an agricultural site in Hesse, Germany,
      demonstrates in principle, the applicability of the critical load concept for O3.
      Comparisons of diurnal variation of stomatal uptake and AOT40 showed that a major
      part of toxicologically effective stomatal uptake occurred before noon whereas
      the AOT40 values were dominated by the O3 concentrations during afternoon. In
      other words, the AOT40 exposure index do not adequately address the O3 burden
      during hours when plants are sensitive to O3 uptake. However, due to the
      differences in radiation, air temperature and humidity between the chamber and
      the ambient microclimates, a derivation of flux-response relationships from
      chamber experiments is likely to be questionable, especially for species rich
      ecosystems: Here, without any changes in the pollution climate, significant
      modifications of species composition as well as an earlier beginning of the
      growing season has been previously observed. To overcome the problems associated
      with chamber-derived flux-response relationships, a new experimental and
      modelling concept, was developed. The approach, briefly described in this paper,
      combines methods in air pollution toxicology and micrometeorology. As an analogy
      to the free-air fumigation concept, O3 is released into the air by an injection
      system above the plant canopy. The assessment of dispersion and surface
      deposition of O3 released is based on Lagrangian trajectory modelling. Depending
      on wind direction and velocity, atmospheric stratification and surface roughness,
      without any disturbance of the microclimate and micrometeorology, several sub
      areas can be identified around the source position with differing deposition
      rates above the ambient level. Taking into account the actual O3 background
      deposition, deposition rates and vegetation responses observed in these sub-areas
      can easily be used to derive flux-effect relationships under ambient conditions
      and more realistic limiting values to protect our environment.

PMID- 12804833
TI  - Tobacco clones derived from tissue culture with supersensitivity to ozone.
AB  - At least two supersensitive tobacco somaclones were obtained from tissue culture
      (TC) , when this approach was used to asexually propagate Bel-W3 tobacco
      indicator plants. These somaclones can detect as low as 30 ppb ozone for a 4-h
      exposure duration both within CSTR exposure chambers and in ambient air.
      Comparison of the injury index and their coefficient of variance showed that the
      TC plantlets usually have more uniform performance in response to ozone in
      addition to their higher sensitivity. A quick regeneration procedure was
      established to preserve the supersensitive germplasm immediately when it was
      found. The TC plantlets will flower and produce seed similar to seed-grown
      tobacco. The TC approach proved to be a better propagation system for valuable
      indicator plant species. The mechanism that causes the variation and the possible
      difference in their genome from seed-grown tobacco is still unknown. Further
      studies are needed in the future to determine if factors in the TC system may be
      responsible for the sensitivity difference.

PMID- 12804834
TI  - Intradermal immunization for rabies prophylaxis: issues to be considered in India
      and other developing countries.

PMID- 12804835
TI  - Route of administration is the prime determinant of IgA and IgG2a responses in
      the respiratory tract of mice to the cold-adapted live attenuated influenza A
      donor strain A/Leningrad/134/17/57.
AB  - Serum antibody and antibody secretory cell (ASC) responses to the cold-adapted
      (CA) live attenuated influenza A donor strain A/Leningrad/134/17/57 in BALB/c
      mice were determined in the lungs and mediastinal lymph nodes after
      administration by the intranasal, subcutaneous and intramuscular routes. Both
      types of response were greatest when an inoculum consisting of 10(6.5) 50% egg
      infectious doses (EID(50)) was administered twice intranasally at an interval of
      3 weeks. Serum responses by the intramuscular route were much higher than by the
      subcutaneous route but, at doses of 10(6.5-7.5) EID(50), were still lower than
      that obtained with two doses of an intranasal inoculum of 10(6.5) EID(50). Virus
      specific ASC responses for IgA and IgG2a were obtained in the lungs and
      mediastinal lymph nodes of mice inoculated with 10(6.5) EID(50) by the intranasal
      route. However, ASC responses after inoculation by either the subcutaneous or
      intramuscular routes were barely detectable, even at doses as high as 10(7.5)
      EID(50). These results confirm that intranasal administration of live vaccines
      induces far higher virus-specific IgA and IgG2a responses in the respiratory
      tract of mice than can be achieved by parenteral administration and that serum
      antibody levels induced by parenteral vaccination are unrelated to the
      respiratory ASC response.

PMID- 12804836
TI  - Efficacy of commercial and field-strain Mycobacterium paratuberculosis
      vaccinations with recombinant IL-12 in a bovine experimental infection model.
AB  - The efficacy of commercial (Strain 18) and field-isolate paratuberculosis vaccine
      preparations was investigated. The effect of prior exposure to Mycobacterium
      paratuberculosis and the adjuvant effect of rIL-12 on vaccine efficacy were also
      tested. Both Strain 18 and field-isolate vaccines induced strong local, systemic
      and enteric IFN-gamma responses. A significant reduction in mycobacterial
      colonization was observed when calves were vaccinated with the field-isolate
      prior to challenge, but not following vaccination with Strain 18 vaccine.
      Vaccination with rIL-12 prevented infection in some calves but its overall effect
      on IFN-gamma response and total mycobacterial load was not statistically
      significant. Efficacy of paratuberculosis vaccines may be enhanced if calves are
      vaccinated prior to M. paratuberculosis exposure with field-isolate vaccine
      instead of Strain 18 vaccine currently in use.

PMID- 12804837
TI  - DNA vaccination protects against botulinum neurotoxin type F.
AB  - A DNA vaccine was constructed which expressed the binding domain of Clostridium
      botulinum neurotoxin serotype F fused to a signal peptide. Three intra-muscular
      doses fully protected Balb/c mice against 10(4) MLD of serotype F toxin. Priming
      of the immune response by DNA vaccination followed by a single booster with type
      F binding domain protein resulted in high levels of antibody against the binding
      domain. This study demonstrates the utility of DNA vaccination for protection
      against botulinum neurotoxin type F and indicates that a prime-boost regimen
      could be an efficient method of generating antibody for passive immune therapy in
      cases of botulism involving serotype F toxin.

PMID- 12804838
TI  - Analysis of epitope recognition of antibodies induced by DNA immunization against
      hemagglutinin protein of influenza A virus.
AB  - In an effort to find efficient DNA vaccine candidates, cDNA of influenza A virus
      hemagglutinin (HA) gene and several derived mutants were injected into mice using
      a gene gun. Mice immunized with HA1 DNA, with or without a membrane domain,
      showed a humoral immune response and the survival rate against homologous virus
      challenge was comparable to that of mice injected with HA DNA. In order to
      analyze epitopes recognized by antibodies induced by gene gun immunization, we
      used a binding assay employing the chimeric HA protein method. Serum antibodies
      of mice immunized with HA DNA recognized the HA1 domain but not the HA2 domain.
      In addition, antisera obtained from mice immunized with HA1 DNA reacted with each
      of the known antigenic sites on the HA1 domain, similar to the results obtained
      with HA DNA immunization.

PMID- 12804839
TI  - Relationship between the immune response and protection conferred by new designed
      inactivated vaccines against ovine enzootic abortion in a mouse model.
AB  - Chlamydophila abortus is a gram-negative obligate intracellular bacterium and the
      etiological agent of ovine enzootic abortion (OEA), an economically important
      disease in many countries. Inactivated vaccines have been reported to induce
      immunity in ewes and they have been used for many years. However, some outbreaks
      have been reported in correctly vaccinated flocks, so it is clear that new
      vaccines are necessary to address adequate protection and to avoid the shedding
      of the microorganism. This idea lead us to design inactivated vaccines, in a
      previously established mouse model, evaluating different inactivation procedures
      and new adjuvants. To assess the protection conferred, the results were analyzed
      on the basis of clinical signs and the isolation of C. abortus from spleen. These
      findings were correlated with the immune response induced by the vaccines, as
      determined by the production of C. abortus-specific IFN-gamma and IL-4 from
      splenocyte cultures and the detection of IgG isotypes in serum. BEI was found to
      be the best C. abortus-inactivation procedure. The inactivated vaccines adjuvated
      with QS-21 (QS) or Montanide 773 (M7) induced the best protection both against
      homologous and heterologous challenge, with an adequate (Th1-like) immune
      response. Finally, these selected vaccines were evaluated in a pregnant mouse
      model, in which they were seen to confer good protection and to avoid the C.
      abortus persistence in uterus after delivery. With these results, this mouse
      model could be considered as an adequate tool for selecting and optimizing
      effective vaccines against OEA.

PMID- 12804840
TI  - Correlation of haemagglutinin-neuraminidase and fusion protein content with
      protective antibody response after immunisation with inactivated Newcastle
      disease vaccines.
AB  - The correlation between the antigen content of inactivated Newcastle disease (ND)
      oil emulsion-vaccines and the serological response after immunisation was
      studied. The haemagglutinin-neuraminidase (HN) and fusion (F) proteins of
      Newcastle disease virus (NDV) were quantified in 33 inactivated oil-adjuvanted ND
      vaccines using isopropylmyristate (IPM)-extraction and antigen ELISAs. These
      commercial vaccines differed in NDV-vaccine strain, the method applied to
      inactivate the vaccine virus, the vaccine valence and the composition of the oil
      emulsions. Large differences, up to 100-fold, in the antigen quantities present
      in different vaccines were found. The NDV-HN content and the NDV-F content of the
      vaccines both highly correlated with the haemagglutination-inhibiting (HI)
      antibody titres after immunisation. These correlation's were found over a 10,000
      fold range of applied antigen. The antigen content of the oil emulsion-vaccines
      also highly correlated with virus neutralising antibody titres. The presence of
      serum HI antibody titres in individual specific pathogens free (SPF)-chickens
      after immunisation with inactivated ND vaccines was highly indicative for
      clinical protection against challenge with the virulent NDV-Herts strain. Our
      results are the first to demonstrate that the protective serological response
      after immunisation highly correlates with the antigen content of oil-adjuvanted
      vaccines.

PMID- 12804841
TI  - Serum antibodies induced by intranasal immunization of mice with Plasmodium vivax
      Pvs25 co-administered with cholera toxin completely block parasite transmission
      to mosquitoes.
AB  - Transmission-blocking vaccines (TBVs) targeting ookinete surface proteins
      expressed on sexual-stage malaria parasites are considered one promising strategy
      for malaria control. To evaluate the prospect of developing non-invasive and easy
      to-administer mucosal malaria transmission-blocking vaccines, mice were immunized
      intranasally with a Plasmodium vivax ookinete surface protein, Pvs25 with a
      mucosal adjuvant cholera toxin (CT). Immunization induced significant serum IgG
      with high IgG1/IgG2a ratio (indicative of Th-2 type immune response). Feeding
      Anopheles dirus mosquitoes with mixtures of immune sera and gametocytemic blood
      derived from vivax-infected volunteer patients in Thailand significantly reduced
      both the number of midgut oocysts as well as the percentage of infected
      mosquitoes. The observed transmission-blocking effect was dependent on immune
      sera dilution. This study demonstrates for the first time that the mucosally
      induced mouse immune sera against a human malaria ookinete surface protein can
      completely block parasite transmission to vector mosquitoes, suggesting the
      possibility of non-invasive mucosal vaccines against mucosa-unrelated important
      pathogens like malaria.

PMID- 12804842
TI  - Immunization with recombinant Calmette-Guerin bacillus (BCG)-hepatitis C virus
      (HCV) elicits HCV-specific cytotoxic T lymphocytes in mice.
AB  - Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in
      preventing the spread of hepatitis C virus (HCV), an effective HCV vaccine should
      be capable of eliciting HCV-specific CTLs. In the present study, we assessed the
      capability of a novel recombinant vaccine using an attenuated tuberculosis
      bacillus, Calmette-Guerin bacillus (BCG), as a vaccine vehicle to elicit HCV
      specific CTLs. BCG was engineered to express the CTL epitope of HCV-non-structure
      protein 5a (NS5a) as a chimeric protein with alpha antigen of mycobacteria.
      Immunization with this recombinant BCG elicited major histocompatibility complex
      class I-restricted CD8(+) HCV-NS5a-specific CTLs in mice. Immunized mice showed a
      substantial reduction in the vaccinia virus titer compared with control mice when
      the immunized mice were challenged with a recombinant vaccinia virus expressing
      HCV-NS5a genes. These findings provide evidences for the possibility of BCG as a
      vaccine vector and its continued exploration as a vehicle for eliciting HCV
      specific immunity.

PMID- 12804843
TI  - Immunity to diphtheria among refugees in southern Italy.
AB  - This study assessed the immune status against diphtheria of a sample of refugees
      (mainly Kosovars and Kurds) in southern Italy (Puglia). The 54.8% of 1128
      subjects showed full protection against diphtheria, 30.1% had basic protection
      and 15.1% resulted seronegative for antitoxin antibody. Only from 45.9 to 73.9%
      of 0-10 years old refugees were fully protected while from 12.3 to 24.2% were
      seronegative to diphtheria with the poorest protection rate among Kurdish
      children from Turkey. Kosovars showed the highest protection rate to diphtheria
      whereas data suggest a probable endemic level of diphtheria in Iraq. The
      screening of refugees revealed a low coverage rate for diphtheria, especially in
      children, probably due to deterioration of the health service infrastructure or
      intermittent basic health care in the country of provenience. In terms of public
      health measures, there is the need of administering booster doses to all refugees
      coming into Italy and into other host countries to increase the coverage rate
      against diphtheria. The implementation of the immunization programs against
      diphtheria in the countries of provenience is also strongly recommended.

PMID- 12804844
TI  - Effectiveness of influenza vaccination of children with recurrent respiratory
      tract infections in reducing respiratory-related morbidity within the households.
AB  - To evaluate the effectiveness of influenza vaccination in reducing respiratory
      related morbidity among children with recurrent respiratory tract infections
      (RRTIs) and their household contacts, 127 children aged 6 months-9 years (78
      males; median age, 3.7 years) with a history of RRTIs (>/=6 episodes per year if
      aged >/=3 years; >/=8 episodes per year if aged <3 years) were randomized to
      receive the intranasal virosomal influenza vaccine (n=64 with 176 household
      contacts) or a control placebo (n=63 with 173 household contacts). During
      influenza season, the vaccinated children had fewer respiratory infections,
      febrile respiratory illnesses, prescribed antibiotics and antipyretics, and
      missed school days than the controls, and similar benefits and a reduction in the
      loss of parental work were observed among their household contacts. This study
      shows that the benefits of influenza vaccination extend to children with RRTIs
      and their family members and encourages to recommend its use in such children.

PMID- 12804845
TI  - Immunogenicity and safety of a novel IL-2-supplemented liposomal influenza
      vaccine (INFLUSOME-VAC) in nursing-home residents.
AB  - Influenza and its complications account for substantial morbidity and mortality,
      especially among the elderly. In young adults, immunization provides 70-90%
      protection, while among the elderly the vaccine may be only </=50% effective;
      hence, the need for new, more immunogenic vaccines. We compared the safety and
      immunogenicity of a novel, interleukin-2 (IL-2) -supplemented trivalent liposomal
      influenza vaccine (designated INFLUSOME-VAC) with that of a commercial trivalent
      split virion vaccine in community-residing elderly volunteers (mean age 81 years)
      in winter of 2000/2001. Eighty-one individuals were randomly assigned to be
      vaccinated intramuscularly, either with the standard vaccine (n=33) or with
      INFLUSOME-VAC (n=48) prepared from the former. The two vaccines contained equal
      amounts of hemagglutinin (HA) ( approximately 15 microgram of each viral strain);
      INFLUSOME-VAC consisted of liposomal antigens admixed with liposomal human IL-2
      (Lip IL-2) (33 microgram = 6x10(5) IU/dose). At 1 month post-vaccination,
      seroconversion rates (tested by hemagglutination inhibition) for the A/New
      Caledonia (H1N1) and A/Moscow (H3N2) strains were significantly higher (P=0.04)
      in the INFLUSOME-VAC group (65 versus 45%, 44 versus 24%, respectively).
      Moreover, INFLUSOME-VAC induced a greater anti-neuraminidase (NA-N2) response
      (P<0.05). Anti-IL-2 antibodies were undetected, and no increase in anti
      phospholipid IgG antibodies was found in the INFLUSOME-VAC group. Adverse
      reactions were similar in both groups. Thus, INFLUSOME-VAC appears to be both
      safe and more immunogenic than the currently used vaccine in the elderly.

PMID- 12804846
TI  - Immunogenicity of 10 and 20 microgram hepatitis B vaccine in a two-dose schedule.
AB  - Healthy subjects (15-50 years old) were randomised to receive, intramuscularly,
      10 or 20 micrograms of a yeast-derived recombinant hepatitis B vaccine
      (Heberbiovac HB) on a two-dose (0-1) schedule. Anti-hepatitis B surface antigen
      antibodies (HBsAb) were determined at 2, 3 and 6 months. Twenty micrograms
      immunisation yielded 96.3% seroprotection (HBsAb >10 IU/l) at t=3, which
      persisted to 97.2% at t=6. The 10 microgram group resulted in 87.4%
      seroprotection at t=3 and 81% at t=6, but reached >95% among subjects <21 years
      old, both at t=3 and 6. It is concluded that the vaccine used is highly
      immunogenic and the two-dose 20 microgram immunisation can be used in all age
      groups and 10 micrograms in subjects up to 20 years. These schedules can result
      in significantly better compliance and cost-effectiveness of the vaccination
      programs.

PMID- 12804847
TI  - Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV
      infected rhesus macaques and HIV-infected individuals.
AB  - Recent contributions have demonstrated that actively secreted Tat protein plays
      an important functional role in human immunodeficiency virus-1 (HIV-1) infection
      and that Tat antibodies might interfere with disease progression by blocking the
      protein extracellularly. In this context we have studied the recognition of
      several Tat mutants as well as various synthetic Tat fragments by anti-Tat
      monoclonal antibodies and by IgG antibodies from a large collection of slow and
      fast-progressor infected individuals. We have also tested the sera from
      simian/human immunodeficiency virus (SHIV)-infected macaques with these Tat
      peptides. Important differences were found between long-term non-progressors and
      fast-progressors, and between human and monkey sera in terms of antibody
      specificity. Rabbits and macaques were immunised with several Tat peptides and we
      found that certain antibody subsets from immunised animals recognised the cognate
      protein Tat and had the capacity to inhibit Tat-induced apoptosis of T cells.
      Such antibodies might be important for controlling Tat-induced death in cells
      uninfected by HIV-1.

PMID- 12804848
TI  - Cellulose beads bound to cellulose binding domain-fused recombinant proteins; an
      adjuvant system for parenteral vaccination of fish.
AB  - A recombinant form of the outer membrane protein (A-layer protein) associated
      with atypical Aeromonas salmonicida was expressed, fused to a cellulose binding
      domain (CBD) isolated from Clostridium cellulovorans. The resultant chimerical
      protein was bound to either Sigmacell 20((R)) or Orbicell cellulose particles.
      Common goldfish were injected intraperitoneally with the cellulose-protein
      complex and blood serum antibody levels produced against A-protein were examined
      weekly by means of ELISA. These titers were compared to those induced by
      immunization of goldfish with the same protein, with or without Freund's
      incomplete adjuvant, as well as to a standard bacterin-adjuvant system. Small
      Orbicell beads (1-10 microM) induced antibody levels that were equal to the
      titers produced by the adjuvanted protein and bacterin formulae. In comparison,
      the larger Sigmacell particles (10-20 microM) proved to be poor
      immunopotentiators. The long-term titer elicited from a single injection of A
      protein bound to Orbicell beads was equivalent to that induced by two injections.
      All the vaccinated fish demonstrated memory to the A-layer protein after exposure
      to a pathogenic load of atypical A. salmonicida with Orbicell treated fish
      displaying the highest titer. No direct correlation was found between the
      presence of anti-A-protein antibodies and protection against infection. The paper
      describes a simple and safe method to increase the potential immunogenicity of
      soluble recombinant proteins by employing relatively inexpensive cellulose
      particles.

PMID- 12804849
TI  - Hepatitis A vaccine: immunogenicity following administration of a delayed
      immunization schedule in infants, children and adults.
AB  - Current immunization schedules for hepatitis A vaccine specify administration of
      a booster within 6-12 or 6-18 months of the primary dose. However, there may be
      circumstances that disrupt this schedule and the efficacy of administering a
      booster beyond the recommended time is a practical concern for healthcare
      providers. In this study, a booster was administered to 268 participants (137:
      <18 years old), an average of 27 months (range 20-31) after the primary dose. In
      those tested after the booster, the median anti-HAV GMT was 1544 milli
      international units per milliliter (mIU/ml). Response to a delayed booster was
      strong in children over 2 years old (GMT 1500-1960 mIU/ml) and adults (GMT 1622
      mIU/ml), but was significantly lower in children under 2 years old (GMT 1109
      mIU/ml). Findings suggest a booster administered 20-31 months after the primary
      dose is immunogenic and GMT in persons >2 years of age were comparable to those
      seen in adults and children who receive hepatitis A vaccine per schedule.

PMID- 12804850
TI  - Intranasal immunization with formalin-inactivated virus vaccine induces a broad
      spectrum of heterosubtypic immunity against influenza A virus infection in mice.
AB  - It has been known that influenza A virus infection induces a cross-protective
      immunity against infection by viruses with different subtypes of viral envelope
      proteins, hemagglutinin (HA) and neuraminidase (NA). This heterosubtypic immunity
      is generally mediated by cytotoxic T lymphocytes (CTL) reactive to specific
      epitopes in the viral internal proteins, such as nucleoprotein and matrix
      protein. By contrast, immunization with inactivated virus antigens has been
      thought to be unable to generate heterosubtypic immunity, since inactivated
      antigens do not usually induce CTL responses. However, we show that intranasal
      immunization with formalin-inactivated intact virus, but not ether-split
      vaccines, induced a broad spectrum of heterosubtypic protective immunity in mice.
      The protection may be mediated by the mucosal immune response, most likely
      secretory IgA antibodies to the viral proteins. This approach may overcome
      limitations in the efficacy of inactivated influenza vaccines and confer potent
      immunity to humans against viruses with new pandemic potential.

PMID- 12804851
TI  - Heterologous boosting increases immunogenicity of chimeric papillomavirus virus
      like particle vaccines.
AB  - Chimeric human papillomavirus virus-like particles (HPV cVLPs), containing the
      HPV16 non-structural protein E7, are potent vaccines for inducing antigen
      specific protective immunity against HPV-transformed tumors in animal models.
      Previous data demonstrated that the effectiveness of cytotoxic T lymphocyte (CTL)
      induction after repetitive vaccination with the same cVLP, and thus vaccine
      efficacy, is limited by the presence of neutralizing antibodies induced after the
      first application. Here, we determined if altering the route of vaccine delivery
      or incorporation of the target antigen into VLPs of a heterologous papillomavirus
      type could overcome inhibition of MHC class I antigen presentation by
      neutralizing antibodies, resulting in a boosting of CD8(+) T-cell responses
      against the incorporated antigen, HPV16 E7. Mucosal delivery of cVLPs resulted in
      detection of systemic E7-specific CD8(+) T cells, however, these routes were not
      able to bypass the inhibitory effect of circulating antibodies against homologous
      VLP types. In contrast, mice immunized and boosted with heterologous cVLPs
      containing HPV16 E7 showed a higher frequency of E7-specific T cells in vitro and
      displayed reduced tumor growth in a therapeutic setting compared to mice treated
      with homologous cVLPs. The data indicate that the use of different cVLP types for
      prime/boost regimens is a promising strategy to increase the efficacy and
      usefulness of cVLP-based vaccines for the treatment of cervical neoplasia.

PMID- 12804852
TI  - A glycosylphosphatidylinositol anchor signal sequence enhances the immunogenicity
      of a DNA vaccine encoding Plasmodium falciparum sexual-stage antigen, Pfs230.
AB  - Mammalian expression vectors encoding region C of malaria transmission-blocking
      vaccine candidate Pfs230 (aa 443-1132) with and without a 3'
      glycosylphosphatidylinositol (GPI) anchor signal sequence were tested for their
      immunogenicity in mice. The plasmid containing the GPI anchor signal sequence
      consistently induced higher titers of anti-Pfs230 antibodies using three delivery
      systems: intramuscular (i.m.), intradermal (i.d.), and gene gun (g.g.). In
      contrast, the isotype profile elicited varied depending on the delivery system
      and was not effected by the presence of the GPI anchor sequence. Both gene gun
      and intradermal administration induced primarily an IgG1 response, while
      intramuscular injection induced both IgG1 and IgG2a antibodies. Regardless of the
      mode of delivery, all the plasmids encoding Pfs230 region C primed for a mixed
      IgG1/IgG2a response to an intraperitoneal (i.p.) injection of E. coli-produced
      recombinant Pfs230 region C. None of these vaccination strategies were more
      effective than r230/MBP.C alone in generating malaria transmission-blocking
      immunity.

PMID- 12804853
TI  - Epidemiology and economic impact of varicella in immunocompetent children in
      Spain. A nation-wide study.
AB  - The epidemiology and burden of varicella was assessed through the prospective
      study of 683 children under 15 years, by 58 primary care paediatricians working
      on seven autonomous communities of Spain. The mean age was 4.5+/-2.7 years, and
      566 (83%) were secondary cases. There were 111 complications in 101 children
      (14.8%), skin superinfection being the most frequent (8.9%), followed by
      respiratory tract (4.5%) and eye (2.2%) infections. The mean number of visits to
      the paediatric clinic was 1.42 (95% C.I. 1.37-1.47), and 5.6% of the children
      were attended in the emergency department of a hospital previously. All children
      had at least one prescription, being antihistamines and antipyretics the most
      prescribed. Thirteen percent received systemic antibiotics and 11% acyclovir.
      Children were mainly cared by grandparents, and parents were off work for a mean
      of 0.97 days (1.61 if children under 5 years attended day-care facilities; 0.51
      if they did not). Costs derived from medical attention totalled 32.5, and social
      indirect costs were 63.77.

PMID- 12804854
TI  - Foot-and-mouth disease vaccine potency testing: determination and statistical
      validation of a model using a serological approach.
AB  - European foot-and-mouth disease vaccine manufacturers are required to quantify
      the efficacy of their product in accordance with the European Pharmacopoeia (EP).
      The method used most often to establish the potency of foot-and-mouth disease
      vaccines requires viral challenge of vaccinated cattle. Alternative approaches,
      such as challenge-free serological assessments have many advantages over existing
      methods and could be used if robust statistical models could be developed that
      related antibody titres to protection from challenge. Logistic regression
      analysis of data from two independent research laboratories, representing six of
      the seven main serotypes of FMD, permitted the parameterisation of these models
      and indicated that a significant relationship existed between antibody titre and
      probability of protection. Furthermore, no significant differences were observed
      in the parameters of logistic models fitted to different strains within the
      serotypes A, O, and SAT-3, or when strains from serotypes A, O, and Asia-1, or
      SAT-1 and SAT-3, were combined. However, significant differences in the model
      parameters did exist between different laboratories. Using these models a
      bootstrap analysis suggested that for vaccines that induced consistently high
      titres, as few as six to eight individual animals could be used to establish with
      confidence the minimum protective doses that would protect 50% of vaccinated
      animals. We conclude that a serologically evaluated truncated test that
      eliminates the need to virus challenge cattle is a credible alternative for
      quantifying vaccine potency.

PMID- 12804855
TI  - Salmonella DNA adenine methylase mutants elicit early and late onset protective
      immune responses in calves.
AB  - Salmonellosis is an important disease of livestock and Salmonella contamination
      of livestock-derived food products and effluents pose a significant risk to human
      health. Salmonella vaccines currently available to prevent salmonellosis in
      cattle have limited efficacy. Here we evaluated a Salmonella enterica serovar
      Typhimurium vaccine strain lacking the DNA adenine methylase (Dam) for safety and
      efficacy in calves. Vaccination was safe in calves, and following challenge with
      virulent Typhimurium 4 weeks post-immunization, vaccinated animals exhibited
      significantly lower mortality, diarrhea, and rectal temperatures, as well as
      reduced colonization of gastrointestinal tract and visceral organs compared to
      non-vaccinated control animals. Additionally, early onset protection (competitive
      exclusion) in vaccinated neonatal calves was demonstrated by attenuated clinical
      disease (as measured by rectal temperatures and attitude scores) and reduced
      mortality when challenged with virulent Typhimurium 24h after immunization. Taken
      together, these data suggest that vaccination with Salmonella Dam mutant strains
      confer significant protection against Salmonella infections in cattle via both
      adaptive immunity and competitive exclusion mechanisms.

PMID- 12804857
TI  - Serological criteria for evaluation and licensure of new pneumococcal conjugate
      vaccine formulations for use in infants.
AB  - The World Health Organization (WHO) is undertaking a series of consultations on
      serological criteria for the evaluation and licensure of new
      formulations/combinations or different vaccination schedules of pneumococcal
      conjugate vaccines. The lack of a definitive serological correlate of protection
      and the multiplicity of antigens involved, especially since the clinical efficacy
      of most of the individual serotypes represented in the only licensed vaccine has
      not been established, are hindering the formulation of criteria for licensure of
      new formulations or combinations of the vaccine. This report analyses the various
      options with their relative merits and drawbacks and provides preliminary
      recommendations as guidance to regulatory agencies in evaluating these vaccines
      for the purposes of licensure. More detailed recommendations for production and
      control of pneumococcal conjugate vaccines, including criteria for evaluation for
      licensure, are currently being drafted.

PMID- 12804856
TI  - A genome-based functional screening approach to vaccine development that combines
      in vitro assays and DNA immunization.
AB  - A two-step screening strategy was developed to identify strong immunogenic
      polypeptides with putative vaccine and/or adjuvant activity. In the first step, a
      mycobacterial genomic DNA library was screened in vitro to identify plasmids
      encoding polypeptides that stimulate splenocytes from mycobacteria-immunized mice
      and T cells from PPD-positive healthy donors to produce interferon-gamma. In the
      second step, plasmids were selected for their ability to induce protective
      immunity in a mouse model of tuberculosis following DNA immunization. The
      potential of this approach is illustrated by the identification of a panel of
      immunogenic polypeptides that may be used to engineer a new generation of
      vaccines.

PMID- 12804858
TI  - Cost-effectiveness of a pneumococcal conjugate immunisation program for infants
      in Switzerland.
AB  - OBJECTIVE: To compare projected economic costs and health benefits associated
      with using pneumococcal conjugate heptavalent vaccine as routine immunisation in
      healthy children in Switzerland. DESIGN: A cost-utility analysis was performed
      from both the societal as well as the sickness funds' perspective. SETTING:
      Simulated birth cohorts of 80,000 children (the approximate size of a birth
      cohort in Switzerland) were followed from birth up to age of 5. MAIN OUTCOME
      MEASURES: Reduction in disease burden, costs of vaccination, cost-utility ratio
      (cost per quality-adjusted life year (QALY)). RESULTS: With a vaccine coverage of
      70% vaccination of newborns only would avert 4 deaths, 8 cases of meningitis, 37
      cases of other invasive pneumococcal disease, 150 cases of pneumococcal pneumonia
      and about 2700 cases of otitis media (OM) per year. The net cost of the
      vaccination program would be 22 Mio. CHF per year for society and about 19 Mio.
      CHF for the sickness funds. This results in a cost-utility ratio of 35,700 CHF
      (approximately 26,300 USD (1)) per QALY from the societal perspective and 39,300
      CHF (28,900 USD) per QALY from the sickness funds' perspective. Additional catch
      up vaccination of all infants <24 months in the years after vaccine introduction
      would result in additional benefits at a cost of 33,600 CHF per additional QALY
      gained. However, if the catch-up vaccination should include all children <60
      months, each additional QALY would be gained at a very high cost (162,000 CHF per
      additional QALY). CONCLUSIONS: Routine vaccination of healthy infants <2 years in
      Switzerland can reduce mortality and long term neurologic impairment resulting
      from invasive pneumococcal disease at a reasonable cost-utility ratio.

PMID- 12804859
TI  - Oral immunization of cattle with hemagglutinin protein of rinderpest virus
      expressed in transgenic peanut induces specific immune responses.
AB  - Rinderpest is an acute, highly contagious often fatal disease of large and small
      ruminants, both domestic and wild. Global eradication of rinderpest needs a
      robust, safe and cost-effective vaccine. The causative agent, rinderpest virus
      (RPV) is an important member of the genus Morbillivirus in the Paramyxoviridae
      family. We have generated transgenic peanut (Arachis hypogea L.) plants
      expressing hemagglutinin protein of RPV and report here, the induction of immune
      responses in cattle following oral feeding with transgenic leaves expressing
      hemagglutinin protein without oral adjuvant. Hemagglutinin-specific antibody was
      detected in the serum as confirmed by immunohistochemical staining of virus
      infected cells, and in vitro neutralization of virus infectivity. Oral delivery
      also resulted in cell-mediated immune responses.

PMID- 12804860
TI  - Differences in immunogenicity and vaccine potential of peptides from Schistosoma
      mansoni glyceraldehyde 3-phosphate dehydrogenase.
AB  - Six peptides, A, B1, B, C, D and E derived from the primary sequence of
      Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) were
      selected based on lowest homology to human G3PDH and used for immunization of
      BALB/c mice. Peptides B1 and D induced immunoglobulin (Ig) G1, IgG2a and IgG2b
      antibodies that reacted with native and denatured SG3PDH, and were associated
      with significant (P<0.05) increase in fecundity and burden of challenge worms,
      respectively. Peptides A, B, C and E elicited a modest cellular immune response,
      IgG2a and/or IgG2b antibodies, and no effect on challenge worm burden. In
      contrast, tetrameric multiple antigen peptide (MAP) constructs A, B, C or E
      elicited strong cellular immune responses and production of IgG1 and/or IgG2a and
      IgG2b antibodies against the homologous MAP and peptide and SG3PDH. The immune
      responses were associated with significant (P<0.05) decrease in challenge worm
      burden for MAP B, and significant (P<0.05) reduction in egg count per worm couple
      for MAP C or E. The data together indicated the nature and effect of immune
      responses vary for each SG3PDH-derived peptide.

PMID- 12804861
TI  - Neutralization epitopes of the HIV-1 primary isolate DH012.
AB  - To study HIV-1 primary isolate neutralization, we have used DH012 as a model to
      study the immunogenicity of several DH012 immunogens and determine the potential
      neutralization epitopes in the virus envelope glycoprotein. Previously, we
      identified that DH012 infected animals mount potent neutralizing activity against
      a conformational epitope (CEV) that involves multiple variable regions. In this
      study, we show that the conformational epitope can be reconstituted with one
      gp120 recombinant fragment containing sequences from the V1/V2 loop and the
      bridging sheet of gp120 and a V3 peptide. In contrast to DH012 infection, we
      previously demonstrated that animals immunized with DH012 gp120 induced potent
      neutralizing antibodies directed at the V3 domain of gp120. In this study, a
      second neutralizing activity against the V1/V2 region of gp120 was identified
      from the same guinea pig sera. In summary, several neutralization epitopes are
      identified on DH012, including the CEV, V1/V2, V3, 17b, IgG1b12, and 2G12
      epitopes. Infectious DH012 virus carrying oligomeric envelope appears to raise
      primarily neutralizing antibodies that recognize a discontinuous conformationally
      dependent epitope whereas the monomeric gp120 induces antibodies that are
      primarily directed at epitopes in the V3 and V1/V2 domains. The DH012
      neutralizing epitopes, such as V1/V2 and V3, are either cryptic or poorly
      immunogenic in chimpanzees. However, immunogens, such as gp120, could be designed
      to induce neutralizing activity against epitopes that are poorly immunogenic,
      such as V1/V2 of DH012, in the native envelope glycoproteins.

PMID- 12804862
TI  - CpG ODN 2006 and IL-12 are comparable for priming Th1 lymphocyte and IgG
      responses in cattle immunized with a rickettsial outer membrane protein in alum.
AB  - Immunostimulatory oligodeoxynucleotides containing unmethylated CpG dinucleotides
      (CpG ODN) stimulate IL-12-dependent Th1 dominated cytokine and enhanced IgG
      responses when co-delivered with antigen to mice. However, the CpG ODN sequences
      that are optimal for each mammalian species may differ. Previously, we
      demonstrated that a CpG ODN containing the GTCGTT motif was optimal for
      stimulating bovine B cell proliferation, and induced IL-6, IL-12 and IFN-gamma
      production by peripheral blood mononuclear cells (PBMC). The current study was
      designed to test the hypothesis that the nuclease resistant phosphorothioate
      modified ODN 2006 (TCGTCGTTTTGTCGTTTTGTCGTT) would induce antigen-specific type 1
      cytokine and enhanced IgG responses similar to those induced by IL-12. To test
      this adjuvant effect, calves were immunized with Anaplasma marginale major
      surface protein 2 (MSP2) with alum alone or combined with CpG ODN 2006, non-CpG
      ODN R2006 or IL-12. MSP2-specific IgG1 and IgG2 responses developed more rapidly
      in calves given IL-12, ODN 2006 or ODN R2006, but the highest IgG1 titers were
      obtained in CpG ODN-immunized calves. Antigen-specific lymphocyte proliferation
      and frequency of IFN-gamma-secreting cells were significantly increased in CpG
      ODN 2006- or IL-12-treated calves, and antigen-stimulated PBMC from these calves
      also expressed higher levels of IFN-gamma transcripts and lower levels of IL-4
      transcripts. No differences in IL-10 mRNA expression were detected among the
      groups. These results indicate that CpG ODN 2006 is an effective vaccine adjuvant
      for stimulating both antibody and IFN-gamma mediated cellular immune responses in
      cattle.

PMID- 12804863
TI  - Effective induction of CD8+ T-cell response using CpG oligodeoxynucleotides and
      HER-2/neu-derived peptide co-encapsulated in liposomes.
AB  - CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant
      activity for a wide range of antigens. Of particular interest is their improved
      activity when closely associated with the antigen. The purpose of this study is
      to determine the potential benefit of liposomes as a co-delivery vehicle to
      enhance the adjuvant activity of CpG ODN for a HER-2/neu-derived peptide to
      induce CD8+ T-cell response. Immunization studies were performed to evaluate the
      effectiveness of the liposomal vaccine in BALB/c mice. Mice were immunized with
      p63-71 encapsulated in liposomes alone or in combination with CpG ODN, as well as
      p63-71 alone in saline or with peptide-pulsed dendritic cells (DC) as controls.
      Enzyme-linked immunospot assay (ELISPOT) assay was performed to measure the
      frequency of splenocytes secreting IFN-gamma as a means to determine the antigen
      specific response. It was found that immunization using p63-71 co-encapsulated
      with CpG ODN within the same liposomes enhanced the antigen-specific IFN-gamma
      response by more than 100-fold when compared with mice immunized with p63-71
      alone. Immunization using free CpG ODN plus p63-71 encapsulated in liposomes or
      p63-71 and CpG ODN encapsulated in separate liposomes could not achieve the same
      effect. Using CD8 as a second marker and intracellular flow cytometric analysis,
      it was found that the IFN-gamma response was contributed by CD8+ T-cells,
      confirming the induction of cytotoxic T-lymphocytes (CTL) by this vaccination
      method. This indicates that a close association of HER-2/neu peptide and CpG ODN
      inside liposomes enhances the CTL epitope delivery and induces CD8+ mediated
      immune response. These results suggest that a vaccinal approach using liposome
      delivery system carrying in self-tumoral epitope and CpG ODN as adjuvant may have
      important implications for cancer therapy.

PMID- 12804864
TI  - Comparative reactogenicity and parental acceptability of pertussis vaccines
      administered into the ventrogluteal area and anterolateral thigh in children aged
      2, 4, 6 and 18 months.
AB  - The importance of site of injection of combined pertussis/diphtheria/tetanus
      vaccines was investigated in two single blind studies. In the pilot study, in
      which the research instrument was trialed, 283 children aged 2-18 months received
      whole cell pertussis vaccine (DTPw) by the intramuscular route either into the
      anterolateral thigh or the ventrogluteal site. In the larger randomised study,
      566 children aged 2-18 months were similarly injected with acellular pertussis
      vaccine (DTPa). Adverse reactions monitored after 24h showed the same lower rates
      for both vaccines with ventrogluteal injection compared with anterolateral thigh
      injection for systemic reactions (irritability (P<0.0001), perceived fever
      (P<0.0001), persistent crying/screaming (P<0.0001) and local reactions (bruising
      (P<0.0001) and redness/swelling (P<0.0001)). The Haemophilus influenzae type b
      vaccine (HibTITER) given concurrently in the contralateral site to the pertussis
      vaccine showed the same lower rates in both studies for ventrogluteal injection
      compared with anterolateral thigh injection for local reactions (redness/swelling
      both studies (P<0.0001) and bruising DTPw study (P<0.0001) and DTPa study
      (P<0.0004)).Parental acceptability was greater (P<0.0001) in both studies for
      ventrogluteal injection compared with anterolateral thigh injection.

PMID- 12804865
TI  - Immunogenicity of DNA vaccines that direct the coincident expression of the 120
      kDa glycoprotein of human immunodeficiency virus and the catalytic domain of
      cholera toxin.
AB  - Passive antibody studies unequivocally demonstrate that sterilizing immunity
      against lentiviruses is obtainable through humoral mechanisms. In this regard,
      DNA vaccines represent an inexpensive alternative to subunit vaccine for mass
      vaccination programs designed to induce such responses to human immunodeficiency
      virus type I (HIV-1). At present, however, this vaccine modality has proven
      relatively ineffective at inducing humoral responses. In this report, we describe
      the immunogenicity of DNA vaccines that direct the coincident expression of the
      cholera toxin catalytic domain (CTA1) with that of the human immunodeficiency
      virus type I gp120 through genes either encoded in individual plasmids or in a
      single dicistronic plasmid. In BALB/cJ mice, coincident expression of CTA1 in
      either a separate plasmid or in the dicistronic plasmid in the DNA vaccines
      induced serum IgG responses to gp120 that were at least 1000-fold greater, and
      remained elevated longer than, the analogous responses in mice vaccinated with a
      DNA vaccine that expressed gp120 alone. In addition, mice vaccinated with CTA1
      and gp120 produced significantly more gp120-specific IFN-gamma ELISPOTs than mice
      vaccinated with the gp120 DNA vaccine. Combined, these data show that the
      adjuvant properties of cholera toxin can be harnessed in DNA vaccine modalities.

PMID- 12804866
TI  - Structure-dependent efficacy of infectious bursal disease virus (IBDV)
      recombinant vaccines.
AB  - The immunogenicity and protective capability of several baculovirus-expressed
      infectious bursal disease virus (IBDV)-derived assemblies as VP2 capsids, VPX
      tubules and polyprotein (PP)-derived mixed structures, were tested. Four-week-old
      chickens were immunised subcutaneously with one dose of each particulate antigen.
      VP2 icosahedral capsids induced the highest neutralising response, followed by PP
      derived structures and then VPX tubules. All vaccinated animals were protected
      when challenged with a very virulent IBDV (vvIBDV) isolate, however the degree of
      protection is directly correlated with the levels of neutralising antibodies. VP2
      capsids elicited stronger protective immunity than tubular structures and 3
      micrograms of them were sufficient to confer a total protection comparable to
      that induced by an inactivated vaccine. Therefore, VP2 capsids represent a
      suitable candidate recombinant vaccine instead of virus-like particles (VLPs) for
      IBDV infections. Our results also provide clear evidence that the recombinant
      IBDV-derived antigens are structure-dependent in order to be efficient as vaccine
      components.

PMID- 12804867
TI  - Habitat selection reduces extinction of populations subject to Allee effects.
AB  - Theoretical studies indicate that a single population under an Allee effect will
      decline to extinction if reduced below a particular threshold, but the existence
      of multiple local populations connected by random dispersal improves persistence
      of the global population. An additional process that can facilitate persistence
      is the existence of habitat selection by dispersers. Using analytic and
      simulation models of population change, I found that when habitat patches
      exhibiting Allee effects are connected by dispersing individuals, habitat
      selection by these dispersers increases the likelihood that patches persist at
      high densities, relative to results expected by random settlement. Populations
      exhibiting habitat selection also attain equilibrium more quickly than randomly
      dispersing populations. These effects are particularly important when Allee
      effects are large and more than two patches exist. Integrating habitat selection
      into population dynamics may help address why some studies have failed to find
      extinction thresholds in populations, despite well-known Allee effects in many
      species.

PMID- 12804868
TI  - Behavioral plasticity and virus propagation: the FIV-cat population example.
AB  - A new theoretical approach is proposed to investigate the effect of intra
      individual variability in behavior on the spread of directly transmitted diseases
      within host populations. The classical hawk-dove game is used to describe
      interactions between individuals on a fast time scale (the day). Individuals may
      exhibit both tactics according to their own experience, to environment
      conditions, and to the opponent. They are not able to recognize the
      epidemiological state of their opponents. This fast-time part of the model is
      coupled to a classical compartmental epidemic model describing the demography of
      the population and the transmission of the disease from an infected individual to
      a healthy one on a slow time scale (the year). The model is applied to the case
      of feline immunodeficiency virus (FIV)-domestic cat population system. Our model
      gives rise to different predictions according to values of cost and gain due to
      fights: extinction of the epidemic, FIV endemicity at low, intermediate and high
      prevalence. These predictions are in good agreement with results from domestic
      cat populations living in different environmental conditions.

PMID- 12804869
TI  - Ideal free distributions when resources undergo population dynamics.
AB  - This study examines the influence of optimal patch choice by consumers on
      resource population dynamics and on consumer distribution in a two patch
      environment. The evolutionarily stable strategy which describes animal
      distributions across habitat patches is called the ideal free distribution (IFD)
      strategy. Two mechanisms that lead to the IFD are: (1) direct consumer
      competition such as interference, and (2) exploitative competition for resources.
      This article focuses on the second mechanism by assuming that resources undergo
      population dynamics while consumer abundance is fixed. Two models of resource
      growth are considered in detail: the exponential and the logistic. The
      corresponding consumer IFD is derived for each of these two models, assuming that
      consumers behave adaptively by moving to the patch which provides them with the
      highest fitness. This derivation does not require that resources are at an
      equilibrium, and it provides, for each resource density, the corresponding
      distribution of consumers. The article suggests that adaptive patch choice by
      consumers decreases between patch heterogeneity in resource levels and weakens
      the apparent competition between resources. The results for a single consumer
      population are extended for two competing consumer populations. The corresponding
      IFD is computed as a function of the two consumer densities. This allows for the
      analytical description of isolegs which are the boundary lines, in the two
      consumer density phase space, separating regions where qualitatively different
      habitat preferences are predicted.

PMID- 12804870
TI  - Impulsive control strategies in biological control of pesticide.
AB  - By presenting and analyzing the pest-predator model under insecticides used
      impulsively, two impulsive strategies in biological control are put forward. The
      first strategy: the pulse period is fixed, but the proportional constant E(1)
      changes, which represents the fraction of pests killed by applying insecticide.
      For this scheme, two thresholds, E(1)(**) and E(1)(*) for E(1) are obtained. If
      E(1)>or=E(1)(*), both the pest and predator (natural enemies) populations go to
      extinction. If E(1)(**)<E(1)<E(1)(*), the pest population converges to the semi
      trivial periodic solution while the predator population tends to zero. If E(1) is
      less than E(1)(**) but even if close to E(1)(**), there exists a unique positive
      periodic solution via bifurcation, which implies both the pest and the predator
      populations oscillate with a positive amplitude. In this case, pest population is
      killed to the maximum extent while the natural enemies are preserved to avoid
      extinction. The second strategy: the proportional constant E(1) is fixed
      (E(1)<E(1)(*) firstly), but the pulse period changes. For this scheme, one
      threshold tau(0) for the pulse period tau is obtained. We can reach the same
      target as above by controlling the period impulsive effect tau<tau(0), even if
      close to tau(0). Our theoretical results are confirmed by numerical simulations.

PMID- 12804871
TI  - Bistability in a size-structured population model of cannibalistic fish--a
      continuation study.
AB  - By numerical continuation of equilibria, we study a size-structured model for the
      dynamics of a cannibalistic fish population and its alternative resource. Because
      we model the cannibalistic interaction as dependent on the ratio of cannibal
      length and victim length, a cannibal experiences a size distribution of potential
      victims which depends on its own body size. We show how equilibria of the
      resulting infinite-dimensional dynamical system can be traced with an existing
      method for numerical continuation for physiologically structured population
      models. With this approach we found that cannibalism can induce bistability
      associated with a fold (or, saddle-node) bifurcation. The two stable states can
      be qualified as 'stunted' and 'piscivorous', respectively. We identify a new
      ecological mechanism for bistability, in which the energy gain from cannibalism
      plays a crucial role: Whereas in the stunted population state cannibals consume
      their victims, on average, while they are very small and yield little energy, in
      the piscivorous state cannibals consume their victims not before they have become
      much bigger, which results in a much higher mean yield of cannibalism. We refer
      to this mechanism as the 'Hansel and Gretel' effect. It is not related to any
      individual 'choice' or 'strategy', but depends purely on a difference in
      population size distribution. We argue that studying dynamics of size-structured
      population models with this new approach of equilibrium continuation extends the
      insight that can be gleaned from numerical simulations of the model dynamics.

PMID- 12804872
TI  - Consistency of estimators of the population-scaled recombination rate.
AB  - We consider (approximate) likelihood methods for estimating the population-scaled
      recombination rate from population genetic data. We show that the dependence
      between the data from two regions of a chromosome decays inversely with the
      amount of recombination between the two regions. We use this result to show that
      the maximum likelihood estimator (mle) for the recombination rate, based on the
      composite likelihood of Fearnhead and Donnelly, is consistent. We also consider
      inference based on the pairwise likelihood of Hudson. We consider two
      approximations to this likelihood, and prove that the mle based on one of these
      approximations is consistent, while the mle based on the other approximation
      (which is used by McVean, Awadalla and Fearnhead) is not.

PMID- 12804873
TI  - Covariances among join-count spatial autocorrelation measures.
AB  - Spatial distributions of biological variables are often well-characterized with
      pairwise measures of spatial autocorrelation. In this article, the probability
      theory for products and covariances of join-count spatial autocorrelation
      measures are developed for spatial distributions of multiple nominal (e.g.
      species or genotypes) types. This more fully describes the joint distributions of
      pairwise measures in spatial distributions of multiple (i.e. more than two)
      types. An example is given on how the covariances can be used for finding
      standard errors of weighted averages of join-counts in spatial autocorrelation
      analysis of more than two types, as is typical for genetic data for multiallelic
      loci.

PMID- 12804874
TI  - Correlative coherence analysis: variation from intrinsic and extrinsic sources in
      competing populations.
AB  - The concept of the correlation between two signals is generalized to the
      correlative coherence of a set of n signals by introducing a Shannon-Weaver-type
      measure of the entropy of the normalized eigenvalues of the n-dimensional
      correlation matrix associated with the set of signals. Properties of this measure
      are stated for canonical cases. The measure is then used to evaluate which
      subsets of a particular set of n signals are more or less coherent. This set of
      signals comprises extrinsic, stochastic resource inputs and the population
      trajectories obtained from simulations of a discrete time model of competing
      biological populations driven by these resource inputs. The analysis reveals
      that, at low levels of competition, the correlative coherence of the combined
      system of intrinsic population and extrinsic resource variables is relatively
      low, but increases with increasing variation in the resources. Further, at
      intermediate and high competition levels, the correlative coherence depends more
      strongly on competition than entrainment of stochasticity in the extrinsic
      resource variables. Density dependence has the effect of amplifying variation in
      noise only when this variation is relatively large. Also, chaotic systems appear
      to be entrained by sufficiently noisy environmental inputs.

PMID- 12804875
TI  - The two-locus model of Gaussian stabilizing selection.
AB  - We study the equilibrium structure of a well-known two-locus model in which two
      diallelic loci contribute additively to a quantitative trait that is under
      Gaussian stabilizing selection. The population is assumed to be infinitely large,
      randomly mating, and having discrete generations. The two loci may have arbitrary
      effects on the trait, the strength of selection and the recombination rate may
      also be arbitrary. We find that 16 different equilibrium patterns exist, having
      up to 11 equilibria; up to seven interior equilibria may coexist, and up to four
      interior equilibria, three in negative and one in positive linkage
      disequilibrium, may be simultaneously stable. Also, two monomorphic and two fully
      polymorphic equilibria may be simultaneously stable. Therefore, the result of
      evolution may be highly sensitive to perturbations in the initial conditions or
      in the underlying genetic parameters. For the special case of equal effects,
      global stability results are proved. In the general case, we rely in part on
      numerical computations. The results are compared with previous analyses of the
      special case of extremely strong selection, of an approximate model that assumes
      linkage equilibrium, and of the much simpler quadratic optimum model.

PMID- 12804876
TI  - Metapopulation theory for fragmented landscapes.
AB  - We review recent developments in spatially realistic metapopulation theory, which
      leads to quantitative models of the dynamics of species inhabiting highly
      fragmented landscapes. Our emphasis is in stochastic patch occupancy models,
      which describe the presence or absence of the focal species in habitat patches.
      We discuss a number of ecologically important quantities that can be derived from
      the full stochastic models and their deterministic approximations, with a
      particular aim of characterizing the respective roles of the structure of the
      landscape and the properties of the species. These quantities include the
      threshold condition for persistence, the contributions that individual habitat
      patches make to metapopulation dynamics and persistence, the time to
      metapopulation extinction, and the effective size of a metapopulation living in a
      heterogeneous patch network.

PMID- 12804877
TI  - Solubilization of fullerene into water with fluoroalkyl end-capped amphiphilic
      oligomers-novel fluorescence properties.
AB  - Solubilization of fullerene into water was studied by the use of fluoroalkyl end
      capped acryloylmorpholine oligomers, N,N-dimethylacrylamide oligomers, and
      acrylic acid oligomers. In these fluorinated oligomers, fluoroalkyl end-capped
      acryloylmorpholine oligomers were more effective in solubilizing fullerene into
      water. Interestingly, the aqueous solutions of fullerene were applicable to
      fluorescence analyses.

PMID- 12804878
TI  - Sorption of tributyltin onto a natural quartz sand.
AB  - The aim of this study is to understand the sorption of tributyltin (TBT) onto
      natural quartz sand by classical batch experiments and spectroscopic surface
      analyses. At pH<6, the major species of TBT is the cation TBT(+). Due to the
      presence of both the cationic part and the butyl chains, TBT should present
      amphiphilic properties. For concentrations lower than 40 microM, TBT sorption
      occurs as a homovalent 1:1 cation exchange between either H(+) or Na(+) and
      TBT(+). The increasing affinity of TBT with respect to the different materials
      follows the series kaolinite<<natural sand<treated sand<pure quartz. From XPS
      analyses, where the chemical environment of Sn did not change, indicating
      possible complete reversibility of the TBT sorption, it seems that inner-sphere
      surface complexes could be formed due to the increase in the 3d-level binding
      energy. At TBT concentrations higher than 100 microM, we showed by flotation
      experiments and XPS analysis that the surface becomes hydrophobic. After one
      monolayer was formed, the TBT sorption could thus be due to hydrophobic
      interaction between the butyl chains of the sorbed TBT and those of the TBT still
      available from the bulk solution. This mechanism is consistent with surface
      condensation and the shape of the sorption isotherm.

PMID- 12804879
TI  - Physical and chemical formations of lead contaminants in clay and sediment.
AB  - A possible sink for divalent lead in the environment is clays such as
      montmorillonite that have cation exchange capacities. To assess the reaction, a
      calcium-montmorillonite was mixed with lead perchlorate solutions of varying
      concentrations and at various pH's. The recovered solids were studied by a
      variety of techniques (X-ray photoelectron and infrared spectroscopy, scanning
      electron microscopy, and atomic force microscopy) to determine what, if any,
      alterations occurred. The ion exchange of lead for calcium reduced the hydrated
      water in the clay, and evidence for proton-lead ion exchange at the edges of the
      sheets was observed. Evidence for a second, unexpected, reaction was also
      observed. Small spots (0.2 to 1 microm) of lead enrichment were observed on the
      surface of clay particles. They were also observed on clays recovered from the
      sediment of a Hungarian lake. The results show that lead ions are adsorbed onto
      montmorillonite by two processes: cation exchange and nano- and microparticle
      production. Cation exchange leads to the even distribution of the ions, while the
      production of spots causes the enrichment of lead ions. The production of these
      particles is not expected from the thermodynamic properties of the solution and
      cannot be observed in the absence of clay.

PMID- 12804880
TI  - Microcalorimetric studies of the mechanism of interaction between designed
      peptides and hydrophobic adsorbents.
AB  - To understand the mechanism of interaction between peptides and peptides with
      hydrophobic ligands, the oligomers (GWG, GWWG, GWWWG) were designed and
      synthesized to study adsorption behavior with octyl sepharose and CM-octyl
      sepharose. By batch equilibrium binding analysis and dilution heat of peptide
      solution measurement, the binding isotherm and adsorption enthalpy were obtained
      and the binding thermodynamics parameters were calculated and analyzed. In the
      isotherm analysis, we reveled that the affinity of GWG for both adsorbents is
      stronger than that of GWWG and GWWWG. The results demonstrate that the cation-pi
      interaction between the peptides and the buffer molecules is significant for
      solutions of peptides with tryptophan residues, and the solvation is competitive
      with the hydrophobic interaction between the peptides and the hydrophobic
      ligands. From the dilution heat measurements, we observed an endothermic dilution
      heat for GWG and exothermic for GWWG and GWWWG. All these results indicate that
      the increased tryptophan chain length can promote the solvation behavior of the
      peptides by the peptide-buffer interaction in this buffer system. Comparing the
      types of ligands reveals that the binding affinities of each peptide for the two
      adsorbents are similar. However, the mechanism of adsorption for peptides with
      hydrophobic ligands might be quite different with respect to the binding enthalpy
      between peptides and adsorbents. The adsorption of the peptides on octyl
      sepharose is an entropy-driven process for all the peptides. In contrast, the
      adsorption of CM-octyl sepharose with GWG and GWWG is an enthalpy-driven process,
      whereas that with GWWWG is entropy-driven. These findings indicate that the
      amount of tryptophan controls the characteristics of the peptides and the
      interaction mechanism in the binding procedure. This study of the adsorption
      mechanism of the designed peptide could provide fundamental information for
      peptide purification and amino acid residue behavior in peptide drug design.

PMID- 12804881
TI  - Effect of particle size of activated clay on the adsorption of paraquat from
      aqueous solution.
AB  - This paper describes the effect of particle size on the process of paraquat
      adsorption from aqueous solution onto an activated clay surface at 25 degrees C
      and initial pH 11.0. Measurements of the pore properties of the clay adsorbents
      with three different particle sizes (0.053-0.074 mm, 0.037-0.053 mm, and <0.037
      mm) were carried out. The rates and isotherms of adsorption have been also
      investigated by batch methods under the controlled conditions. From the
      experimental results obtained, the adsorption process can be well described with
      the pseudo-second order model and Freundlich model for adsorption kinetics and
      adsorption isotherm, respectively. In addition, the effect of the particle size
      of the clay adsorbent on the adsorption kinetics was found to be of considerable
      significance; namely, the rate constant (k) of paraquat adsorption by the clay
      adsorbent decreased with increasing particle size. It was concluded that the pore
      properties (i.e., surface area and total pore volume) and particle size of the
      clay adsorbent played a significant role in determining adsorption capacity and
      adsorption rate, respectively.

PMID- 12804882
TI  - Metal ions binding onto a lignocellulosic substrate extracted from wheat bran: a
      NICA-Donnan approach.
AB  - In this study ion binding to solid organic matter was investigated. We used the
      NICA-Donnan model to describe the interaction between Cu(II), Pb(II), and Cd(II)
      ions and a lignocellulosic substrate extracted from wheat bran. Such a material
      represents a very cheap and flexible substrate, which can be used as a natural
      filter to remove toxic metal ions from industrial effluents or applied in the
      decontamination and rehabilitation of abandoned industrial sites. Moreover, such
      a material also represents a very simple model of natural organic matter derived
      from lignin and cellulose, for which there is now a lack of thermodynamic data as
      far as their interaction with toxic metal ions is concerned. Experimental results
      were obtained in various conditions of pH and ionic strength. In our modeling, we
      used the acidity constants and the concentration of sites that were determined in
      a previous work. The parameters deduced from the NICA-Donnan model were also
      compared to thermodynamic data available for other cases of natural organic
      matter, mainly humic substances.

PMID- 12804883
TI  - Flocculation of diatomite by methylated egg albumin.
AB  - A common and inexpensive protein, egg albumin, was applied to the solid-liquid
      separation or flocculation of diatomite. Egg albumin was methylated in a 0.05 M
      HCl methyl alcohol solution at room temperature. About 90% of the carboxylic
      groups of egg albumin could be methylated within 24 h. The adsorption of egg
      albumin onto diatomite at pH 6.8 was remarkably enhanced by methylation. The
      adsorption constant of methylated egg albumin to diatomite at 30 degrees C was
      about 100-fold larger than that of native egg albumin; however, the adsorption
      constant of methylated egg albumin decreased to about 1/100 with temperature
      decreasing from 30 to 6 degrees C. The saturated adsorption amount of egg albumin
      was also increased by the methylation. The flocculating ability of methylated egg
      albumin was examined with a diatomite suspension at 6 and 30 degrees C in the pH
      range from pH 2 to 11. The diatomite suspension was effectively flocculated by
      the addition of small amounts of methylated egg albumin (only 0.5-1 wt% against
      diatomite) over a wide pH range from pH 3 to 10.

PMID- 12804884
TI  - Disproportionation of clustered protein-stabilized bubbles at planar air-water
      interfaces.
AB  - The rate of shrinkage of air bubbles, of initial radius from 50 to 200 microm,
      injected beneath a planar air-water interface has been measured. Bubbles were
      stabilized in solutions of 0.05 wt% gelatin or pure beta-lactoglobulin. It has
      been observed that small size differences between two closely spaced or touching
      bubbles result in markedly divergent rates of shrinkage for the two. By studying
      a number of different initial bubble configurations, it is demonstrated that the
      overall change in bubble size distribution is strongly dependent on local,
      interbubble gas diffusion. In this respect, the strong tendency for the gelatin
      stabilized bubbles to aggregate and shrink, while remaining in contact, produced
      patterns of disproportionation significantly different from those observed with
      beta-lactoglobulin. In beta-lactoglobulin solutions, it was usually found that
      bubbles initially in contact shrank away from each other with time, becoming
      increasingly isolated as a result. A theoretical approach that can exactly
      incorporate the perturbation of local diffusion fluxes due to the proximity of
      two bubbles is presented. This enables one to map a "stability diagram" that
      delineates regions where the larger bubble of a pair will either shrink or grow,
      according to the relative size of the bubbles and their separation. Theoretical
      calculations show that it is possible for a bubble to exhibit more complex
      shrinkage behavior than is predicted by a mean field approach or the Lifshitz,
      Slyozov, and Wagner (LSW) theory of Ostwald ripening for dilute systems. The
      inclusion of dilatational elasticity in the theoretical model introduces
      additional complications, which are also briefly discussed.

PMID- 12804885
TI  - Formation of intermolecular beta-sheet structures: a phenomenon relevant to
      protein film structure at oil-water interfaces of emulsions.
AB  - Oil-in-water emulsions stabilized with beta-lactoglobulin (beta-lg) were made
      using a homogenizer or a high-speed blender. The protein was studied by Fourier
      transform infrared (FTIR) spectroscopy in the raw emulsion, in the bulk phase,
      and at the interface, as a function of pH, oil content, and homogenizing
      pressure. Results show that the amount of adsorbed protein varies with the
      available interfacial area. The protein that remains in the aqueous phase exhibit
      no spectral change, which suggests that homogenization causes no conformational
      modification or reversible ones. Strong and irreversible changes were observed in
      the adsorbed protein. Our findings reveal the formation of intermolecular
      antiparallel beta-sheets upon adsorption due to the protein self-aggregation. As
      deduced from transmission electronic microscopy, this surface aggregation leads
      to the formation of continuous and homogeneous membranes coating the globules.
      The structure of the adsorbed proteins is unaffected by the homogenizing
      pressures used in our study and slightly modified by the pH. FTIR spectroscopy
      allows to characterize the type of aggregates formed at the interface. An
      analysis of the spectra of beta-lg heat-induced gels shows that the aggregates at
      the interface are very close at a molecular scale to those that constitute
      particulate gels near the protein's isoelectric point. Since the type of
      aggregates is similar when the emulsion water phase is pure D(2)O and D(2)O at pD
      4.4, the interface not only seems to induce aggregation, but seems to determine
      the type of aggregation as well. The mechanism that drives the formation of
      particulate aggregates (rather than fine-stranded ones) may reside in strong
      protein-protein interactions that are promoted by adverse oil-protein
      interactions.

PMID- 12804886
TI  - Morphology of RuO2-TiO2 coatings and TEM characterization of oxide sols used for
      their preparation.
AB  - Characterization of RuO(2) and TiO(2) sols of different aging times, obtained by
      forced hydrolysis of appropriate chloride salts, was performed by transmission
      electron microscopy (TEM). The aging time of TiO(2) sols was observed to affect
      the size of particles as well as the crystallinity of the solid phase of the
      sols. The surface morphology of RuO(2)-TiO(2) coatings on titanium, obtained by
      the sol-gel procedure using TiO(2) sols of different aging times and RuO(2) sol
      of fixed aging time, was investigated by scanning tunneling microscopy (STM) at
      three different scan sizes. The STM data indicated uniform microdistribution of
      the coating material (small microroughness) and an increase in nanoroughness with
      the aging time of the TiO(2) sol. The observed increase in real coating surface
      area with increasing TiO(2) particle size confirms the earlier cyclic voltammetry
      results.

PMID- 12804887
TI  - Effective charges of colloidal particles obtained from collective diffusion
      experiments.
AB  - In this work, the collective diffusion coefficient of highly charged colloidal
      particles in dilute dispersions has been measured by means of dynamic light
      scattering. The possibility of obtaining valuable information about the particle
      charge from these data is looked into with the help of electrophoresis
      experiments. Our results suggest that this is possible in the case of slight or
      moderately interacting particles as long as experimental data are properly
      treated. For highly interacting colloids, however, such information could not be
      so reliable, presumably due to certain shortcomings of the experimental technique
      at low angle. The role of charge renormalization is also discussed in this work.

PMID- 12804888
TI  - Synthesis of size-controlled cobalt ferrite particles with high coercivity and
      squareness ratio.
AB  - Cobalt ferrite particles with diameters ranging from a few micrometer to about 15
      nm were synthesized using a modified oxidation process. The fine control of the
      particle size was achieved by introducing various concentrations of Fe(3+) ions
      at the beginning of the reaction. Among the particle sizes obtained by using this
      method, particles with a grain size of about 36 nm showed a magnetization (M(s))
      of 64 emu/g and a maximum coercivity (H(c)) of 2020 Oe at room temperature. The
      corresponding squareness ratio was found to be 0.53.

PMID- 12804889
TI  - A general gel layer model for the transport of colloids and macroions in dilute
      solution.
AB  - A general boundary element methodology for studying the dilute solution transport
      of rigid macroions that contain gel layers on their outer surfaces is developed
      and applied to several model systems. The methodology can be applied to particles
      of arbitrary size, shape, charge distribution, and gel layer geometry. Account is
      also taken of the steady state distortion of the ion atmosphere from equilibrium,
      which makes it applicable to the transport of highly charged structures. The
      coupled field equations (Poisson, ion-transport, low-Reynolds-number Navier
      Stokes, and Brinkman) are solved numerically and from this, transport properties
      (diffusion constants, electrophoretic mobilities, excess viscosities) can be
      computed. In the present work, the methodology is first applied to a gel sphere
      model over a wide range of particle charge and the resulting transport properties
      are found to be in excellent agreement with independent theory under those
      conditions where independent theory is available. It is then applied to several
      prolate spheroidal models of a particular silica sol sample in an attempt to
      identify possible solution structures. A single model, that is able to account
      simultaneously for all of the transport behavior, which does not undergo
      significant conformational change with salt concentration, could not be found. A
      model with a thin (</=1-nm) gel layer at high salt content that expands on going
      to low salt content is able to explain the salt dependence of the intrinsic
      viscosity, but not the electrophoretic mobility. However, a model with a fairly
      thick (2-nm) gel layer at high salt content, which expands slightly (2.5-nm) at
      low salt content, is in fairly good agreement with experiment. In addition, the
      influence of particle charge and the presence of a gel layer on the Scheraga
      Mandelkern parameter are examined. This parameter is proportional to the product
      of the translational diffusion constant and the cube root of the intrinsic
      viscosity. It is found to be very robust with regard to net particle charge as
      well as properties of the gel layer.

PMID- 12804890
TI  - Electrochemical behavior of pyrroloquinoline quinone immobilized on silica gel
      modified with zirconium oxide.
AB  - Pyrroloquinoline quinone (PQQ) was immobilized on the silica gel surface modified
      with zirconium oxide, designated as Si:Zr, by the carboxylic groups of the PQQ
      molecule and the zirconium oxide on the silica surface. The electrochemistry of
      PQQ immobilized on the Si:Zr matrix, incorporated in a carbon paste electrode,
      was evaluated using the cyclic voltammetry technique. The Si:Zr:PQQ-modified
      electrode showed a redox couple at E(m)=(E(pa1)+E(pc))/2=-0.150 V vs SCE at pH 7,
      close to that observed in aqueous solution, and another oxidation peak, E(pa2)=
      0.100 V vs SCE. Studies in different pH solutions in the range of 3-7 showed that
      the first oxidation peak, E(pa1), is highly dependent on the solution pH shifting
      from to -0.175 to 0.100 V vs SCE, while E(pa2) remains practically constant at
      0.100 V as the pH decreases from 7 to 3. The immobilized PQQ electrode presented
      the property to electrocatalyze the NADH at 150 mV vs SCE. The effect of addition
      of Ca(2+) ions on the electrode electroactivity for the NADH oxidation was also
      verified. Different from that observed for the PQQ immobilized on other electrode
      materials, the Ca(2+) ions did not influence the electrocatalytical response;
      however, the electrode stability was considerably improved in the presence of
      Ca(2+) ions, indicating that the matrix surface has a great influence on the
      electrochemical behavior of PQQ.

PMID- 12804891
TI  - Piezoelectric quartz crystal impedance and electrochemical impedance study of HSA
      diazepam interaction by nanogold-structured sensor.
AB  - Human serum albumin (HSA) was immobilized on the surface of colloidal Au and
      exposed to diazepam. Colloidal Au were at first self-assembled on the gold
      electrode through the thiol groups of a 1,6-hexanedithiol monolayer. The real
      time course of the resonant frequency and equivalent circuit parameters of the
      sensor during the protein-diazepam binding was determined for the first time by
      piezoelectric quartz crystal impedance (PQCI). On the basis of the
      multidimensional information provided by the PQCI analysis, it was concluded that
      the decrement of the observed frequency was mainly ascribable to the mass loading
      on the sensor surface. Compared with a bare gold electrode, the gold electrode
      self-assembled from nanogold colloids exhibits maintained biocompatibility,
      increased capacity, and more bioactivity. Cyclic voltammetry and electrochemical
      impedance techniques were used to investigate the immobilization of HSA and the
      interaction between HSA and diazepam. Results testified that gold colloid could
      play the role of an efficient electron-conducting tunnel and have a very high
      ratio of surface to volume. Additionally, the kinetics of the binding process was
      investigated. The estimated binding constant (K) and the number of binding site
      (n) on one HSA molecule were 1.66 x 10(6) mol l(-1) and 1.28, respectively.

PMID- 12804892
TI  - Expressions for evaluating the possibility of slip at the liquid-solid interface
      in open tube capillary electrochromatography.
AB  - In this work, expressions are constructed and solved that describe the velocity
      field of electroosmotic flow (EOF) in open tube capillary electrochromatography
      (CEC) systems when the possibility of having unequal tangential velocities at the
      liquid-solid interface is considered and a slip condition is employed as a
      boundary condition for the velocity of the EOF at the capillary wall. The coupled
      equations of hydrodynamics (momentum balance equation) and electrostatics
      (Poisson equation) are solved numerically in order to obtain the distribution of
      the velocity field as well as the value of the volumetric flow rate in the open
      tube. Also, expressions for the velocity field and the volumetric flow rate of
      the EOF are presented that are valid for certain electrolytic systems and for
      certain parameter values for which analytical solutions to the momentum balance
      and Poisson equations could be obtained. The results presented in this work
      indicate that having slip in the velocity of the EOF at the wall of the capillary
      could (i) substantially increase the electroosmotic velocity in the plug-flow
      region of the radial domain of the open capillary tube and (ii) increase the
      portion of the radial domain of the open capillary tube where the velocity of the
      EOF has a plug-flow profile, which in turn could increase the average velocity
      and volumetric flow rate of the EOF in the open capillary tube. Furthermore, the
      modeling approach and the results presented in this work indicate a method for
      experimentally evaluating the possibility of having slip in the velocity of the
      EOF at the capillary wall.

PMID- 12804893
TI  - Electrochemical behavior of aqueous acid perrhenate-containing solutions on noble
      metals: critical review and new experimental evidence.
AB  - The actual state of the art in the reduction of perrhenate ions on noble metals
      is reviewed and discussed. Also, with the aim of contributing to better knowledge
      of this process, results of several experiments are presented. For the first
      time, spectroscopic evidence on the nature of the deposited rhenium layer on Pt
      and Rh and the detection of an intermediate in the reduction pathway toward
      metallic rhenium is provided. The role of the substrate in the electroreduction
      of perrhenate ions in aqueous acid media is emphasized, because it is directly
      associated with the formation of different H-containing species as reducing
      agents. Thus, those metals capable of adsorbing H atoms are able to reduce
      ReO(4)(-) to ReO(2) by H(ad) at potentials more positive than that of the
      hydrogen evolution reaction. Moreover, H(ad) reacts with the ReO(2) layer
      previously deposited, resulting in the formation of Re(III)-soluble species,
      which subsequently undergo disproportionation to Re and ReO(2). For metals that
      are not capable of adsorbing H, i.e., Au, molecular hydrogen is the reducing
      agent, leading to the formation of metallic Re. In addition, ReO(4)(-) is
      chemically reduced to metallic Re by hydride.

PMID- 12804894
TI  - Electrokinetic mixing vortices due to electrolyte depletion at microchannel
      junctions.
AB  - Due to electric field leakage across sharp corners, the irrotational character of
      Ohmic electroosmotic flow is violated. Instead, we demonstrate experimentally and
      theoretically evidence of electrolyte depletion and vortex separation in
      electroosmotic flow around a junction between wide and narrow channels. When the
      penetration length of the electric field exceeds the width of the narrow channel
      and if the electric field is directed from the narrow to the wide channel, the
      electromigration of ions diminishes significantly at the junction end of the
      narrow channel due to this leakage. Concentration depletion then develops at that
      location to maintain current balance but it also increases the corner zeta
      potential and the local electroosmotic slip velocity. A back pressure gradient
      hence appears to maintain flow balance and, at a sufficient magnitude, generates
      a pair of vortices.

PMID- 12804895
TI  - Lattice Boltzmann model of microfluidics in the presence of external forces.
AB  - We present here a lattice Boltzmann model in the presence of external force
      fields to describe electrokinetic microfluidic phenomena and consider pressure as
      the only external force to drive liquid flow. Our results from a 9-bit square
      lattice Boltzmann model are in good agreement with recent experimental data in a
      pressure-driven microchannel flow that could not be fully described by
      electrokinetic theory. The differences between the predicted and the experimental
      Reynolds numbers from pressure gradients are well within 5%. Results suggest that
      the lattice Boltzmann model described here is an effective computational tool for
      predicting the more complex microfluidic systems that might be problematic using
      conventional methods.

PMID- 12804896
TI  - Multilaboratory study of the shifts in the IEP of anatase at high ionic
      strengths.
AB  - The zeta-potentials of anatase at pH 2-11 in 0.1, 0.3, 0.5, and 1 moldm(-3) NaI
      were studied using the DT 1200 in three laboratories. At [NaI]=1 moldm(-3) the
      zeta-potentials were positive over the entire pH range. The previously observed
      tendency of the isoelectric point of anatase to shift to high pH at high ionic
      strength (M. Kosmulski, J.B. Rosenholm, J. Phys. Chem. 100 (1996) 11681) and the
      salt specificity of this effect were confirmed. The zeta-potentials obtained in
      different laboratories using DT 1200 are consistent within 3 mV.

PMID- 12804897
TI  - The effect of surface dipoles and of the field generated by a polarization
      gradient on the repulsive force.
AB  - Double-layer and hydration interactions have been coupled into a single set of
      equations because both are dependent on the polarization of the water molecules.
      The coupled equations involve the electric fields generated by the surface charge
      and surface dipoles, as well as the field due to the neighboring dipoles in
      water. The dipoles on the surface are generated through the counterions' binding
      to sites of opposite charge. The equations obtained were employed to explain the
      restabilization observed experimentally at large ionic strengths for colloidal
      particles on which protein molecules were adsorbed. Polar molecules adsorbed on a
      charged surface of colloidal particle can generate a field either in the same
      direction as that generated by the charge or in the opposite direction. The
      effect of the sign of the dipole of the adsorbed polar molecules on the
      interaction between surfaces was also examined.

PMID- 12804898
TI  - Dynamic contact angle and spreading rate measurements for the characterization of
      the effect of dentin surface treatments.
AB  - A new methodology capable of providing reliable and reproducible contact angle
      (theta) data has been employed to study the effect of clinical treatments
      grinding, acid etching, and deproteinization on medial dentin tissue. It is based
      on the application of the ADSA-CD algorithm to the determination of low-rate
      dynamic contact angles, obtained from slowly growing drops, and on contact angle
      measurement, as well as spreading behavior analysis, during the relaxation of the
      system (water on treated dentin) after initial drop growth. The theta data
      obtained were substantially more reproducible than those obtained with classical
      methods. A net effect of the treatment on theta was found, increasing dentin
      wettability: theta (polished) >theta (etched) >theta (deproteinized). The
      spreading rates correlate with the angles and are adequate for the dentin surface
      characterization. ANOVA and SNK tests show that for advancing contact angles the
      means corresponding to all treatments are significantly different. In the
      relaxing phase, mean angle and spreading rates on polished dentin differ
      significantly from those on etched and deproteinized dentin, but the latter do
      not differ significantly from each other.

PMID- 12804899
TI  - X-ray diffraction and X-ray photoelectron spectroscopy studies of Ni-P deposited
      onto carbon fiber surfaces: impact properties of a carbon-fiber-reinforced
      matrix.
AB  - In this work, the Ni-P coating on carbon fiber surfaces was carried out in order
      to improve the impact resistance of carbon fibers-reinforced epoxy matrix
      composites. The fiber surfaces and the fracture behaviors of composites were
      measured in terms of X-ray diffraction spectrometry (XRD), X-ray photoelectron
      spectrometry (XPS), scanning electron microscopy (SEM), and falling weight impact
      testing. From the XRD and XPS measurements, it was observed that Ni-P coating of
      carbon fibers led to an increase in two phases, i.e., microcrystalline and
      amorphous, mainly due to the increase of NiP(2), Ni(3)P, and Ni metal. Energy
      adsorbed by composites through the various fracture mechanisms was seen to be the
      characteristic distinguishing between nontreated and treated fiber-reinforced
      composite systems. The Ni-P alloy technique to improve the impact resistance of
      the composites was shown to be the modification of fiber-epoxy resin interfaces.

PMID- 12804900
TI  - Incipient CdS thin film formation.
AB  - The quality of a final thin film is essentially determined by the processes
      taking place at incipient CdS deposition, which in turn are strongly influenced
      by the physicochemical properties of the substrate and liquid in contact. SEM
      pictures of deposits formed through steady flow of a supersaturated (with respect
      to CdS) solution suggest that initially nuclei are continuously generated on the
      substrate and grow as discrete "surface" particles. With time, these particles
      tend to "coalesce" with neighboring ones, while new nuclei keep forming and
      growing, leading to the formation of a coherent film. There is evidence that
      similar growth patterns prevail in CdS deposition via the chemical bath
      deposition (CBD) process. Based on experimental observations, a simple model is
      developed, which is capable of predicting macroscopically determined film
      characteristics such as the temporal thickness evolution including the "induction
      period." Two cases of the growth pattern are examined theoretically; one based on
      instantaneous surface nucleation (due to its simplicity) and another with a
      constant surface nucleation rate, which appears to be closer to experimental
      observations.

PMID- 12804901
TI  - Micropatterning of Ni particles on a BaTiO3 green sheet using a self-assembled
      monolayer.
AB  - We studied surface modification of ceramic BaTiO(3) green sheets including
      polyvinylbutyral (PVB) as an organic binder and successfully fabricated a
      patterned self-assembled monolayer (SAM) which has a region of amino groups and a
      region of silanol groups on the green sheet. The patterned SAM was then immersed
      in water containing Ni particles that show negative zeta potential in water. Ni
      particles were attracted to the amino groups of the patterned SAM that show
      positive zeta potential by attractive electrostatic interaction. Consequently, a
      micropattern of Ni particles was achieved using a SAM at room temperature in
      water. This process can be used to fabricate a thin uniform internal Ni electrode
      for miniaturized high-performance multilayer ceramic capacitors (MLCC).

PMID- 12804902
TI  - The kinetics and spectral studies of the in situ polyaniline film formation.
AB  - The chemical oxidation of aniline with ammonium persulfate (APS) in an aqueous
      acidic solution to form polyaniline (PANI) films has been studied using the
      quartz crystal microbalance (QCM) technique. The kinetics of the film formation
      was investigated. The reaction exhibited half-order with respect to APS and first
      order to aniline. The effect of temperature on the growth rate of PANI films was
      studied. The activation energy is 39.79 kJ/mol. This is in agreement with the
      corresponding one determined for the chemical polymerization of PANI in the bulk.
      The UV-visible spectra of the PANI films grown onto a glass support immersed into
      the bulk solution were measured. The absorption of the PANI film with time was
      also studied and compared to the growth of the PANI film thickness using the QCM
      technique.

PMID- 12804903
TI  - Rates of transport through a capsule membrane to attain Donnan equilibrium.
AB  - The swelling of a capsule consisting of salt solution and polyelectrolyte,
      surrounded by a membrane, is studied. The membrane allows salt and water to pass,
      but is impermeable to polyelectrolyte molecules. Equilibrium swelling of the
      capsule is governed by Donnan equilibrium. Transport rates of a salt and water
      through the membrane are expressed in terms of a Darcy permeability and a salt
      diffusivity. The governing equations predict that the rate at which equilibrium
      is attained as the external salt concentration varies is controlled by the
      timescale for diffusion of salt, rather than by that for Darcy flow. Experiments
      were performed using capsules with membranes made of covalently linked HSA and
      alginate. The capsule volume varied with a single relaxation rate when the
      external salt concentration was changed, as predicted by theory. This constitutes
      the first step toward a simple method for determining the membrane properties of
      capsules by measuring rates of change of capsule volume.

PMID- 12804904
TI  - Influence of the dynamic contact angle on the characterization of porous media.
AB  - It has been shown recently that the classical Lucas-Washburn equation, often used
      to model the dynamics of liquid penetration into porous media, should be modified
      to take account of the dynamic contact angle between the liquid and the pore.
      Here we show how neglect of this effect can lead to significant errors in
      estimation of the effective pore radius.

PMID- 12804905
TI  - Osmotic behavior of a Nafion membrane in methanol-water electrolyte solutions.
AB  - In this paper, an experimental study was carried out in order to investigate the
      osmotic transport of methanol-water electrolyte solutions through a Nafion
      membrane. The experimental data indicated that the Nafion membrane showed the
      typical anomalous osmotic behavior of charged membranes. The influence of some
      relevant parameters, such as electrolyte concentration difference, weight
      fraction of methanol on solution, and nature of cation was considered. The
      results showed that the osmotic volume flow was decreased with the presence of
      methanol on solvent, but did not alter the anomalous osmotic behavior of the
      membrane.

PMID- 12804906
TI  - Membrane oscillations involving electrokinetic phenomena.
AB  - Semi theoretical models have been proposed to account for the mechanism of
      membrane oscillations involving, electrokinetic phenomena in systems where (i)
      concentration difference deltaC is finite and deltaP is varying but the current
      is fixed, and (ii) deltaC=0, pressure difference deltaP is fixed across the
      membrane and imposed current is fixed. The formalism leads to the van der Pol
      equation in both cases. Computer simulation has also been attempted, which
      indicates oscillations in the former case.

PMID- 12804907
TI  - Catalytic effect of supported metal ion complexes on the induced oxidative
      degradation of pyrocatechol violet by hydrogen peroxide.
AB  - Kinetics of the oxidative degradation of pyrocatechol violet dye (PCV) [2-[(3,4
      dihydroxyphenyl)(3-hydroxy-4-oxocyclohexa-2,5-dien-1-ylidene) methyl]
      benzenesulfonic acid] by H(2)O(2) catalyzed by supported transition metal
      complexes have been studied. The reaction was followed by conventional UV-vis
      spectrophotometer at lambda(max)=440 nm in a buffer solution at pH 5.1. The
      supports used were silica gel and cation exchange resins (Dowex-50W, 2 and 8%
      DVB), while the complexes were [Cu(amm)(4)](2+), [Cu(en)(2)](2+),
      [Cu(ma)(4)](2+), [Co(amm)(6)](2+), and [Ni(amm)(6)](2+) (amm=ammonia,
      en=ethylenediamine, and ma=methylamine). The reaction exhibited first-order
      kinetics with respect to [PCV] and [H(2)O(2)]. The reactivity of the catalysts is
      correlated with the redox potential of the metal ions, the type of support, and
      the amount of supported complexes. The rate of the reaction increases with
      increasing pH and the addition of NaCl. Addition of SDS and CTAB showed
      inhibiting effects. The reaction is enthalpy-controlled as confirmed from the
      isokinetic relationship. A reaction mechanism involved the generation of free
      radicals as an oxidant has been proposed.

PMID- 12804908
TI  - Partial wetting of chemically patterned surfaces: the effect of drop size.
AB  - Partial wetting of chemically heterogeneous substrates is simulated. Three
      dimensional sessile drops in equilibrium with smooth surfaces supporting ordered
      chemical patterns are considered. Significant features are observed as a result
      of changing the drop volume. The number of equilibrated drops is found either to
      remain constant or to increase with growing drop volume. The shape of larger
      drops appears to approach that of a spherical cap and their three-phase contact
      line seems, on a larger scale, more circular in shape than that of smaller drops.
      In addition, as the volume is increased, the average contact angle of drops whose
      free energy is lowest among all equilibrium-shaped drops of the same volume
      appears to approach the angle predicted by Cassie. Finally, contrary to results
      obtained with two-dimensional drops, contact angle hysteresis observed in this
      system is shown to exhibit a degree of volume dependence in the advancing and
      receding angles. Qualitative differences in the wetting behavior associated with
      the two different chemical patterns considered here, as well as differences
      between results obtained with two-dimensional and three-dimensional drops, can
      possibly be attributed to variations in the level of constraint imposed on the
      drop by the different patterns and by the dimensionality of the system.

PMID- 12804909
TI  - Drops impacting a sieve.
AB  - We study experimentally the impact of liquid drops against thin plates pierced
      with small holes. When the drop is larger than the hole, different situations can
      occur: (i) at a small velocity, the drop is entirely captured by the plate; (ii)
      above a threshold speed, some liquid is ejected below the surface. We
      characterize this critical speed and these two different situations, focusing on
      the forces able to slow down the drop. We also quantify the amount of liquid
      ejected out of the hole.

PMID- 12804910
TI  - Surfactant adsorption and Marangoni flow in liquid jets. I. Experiments.
AB  - The adsorption of surfactants at an expanding liquid surface has been studied in
      a gravity-driven laminar water jet with Reynolds numbers in the range from 1000
      to 2000. Surface concentrations of hexadecyltrimethylammonium bromide (C(16)TAB)
      were deduced from ellipsometric measurements, using a calibration made previously
      with neutron reflection. Simultaneous measurements of the velocity profile within
      the jet were made with laser Doppler velocimetry. These two noninvasive
      techniques were able to measure conditions to within 1 mm of the nozzle, where
      rates of surface expansion were as high as 300 s(-1). For the laminar jet without
      surfactant, the measurements are in excellent agreement with CFD calculations and
      with the theoretical result that the surface velocity varies as z(1/3), where z
      is the distance from the nozzle. Close to the nozzle the high rate of surface
      expansion drives both rapid diffusional transport to the surface, and rapid
      convection on the surface, resulting in a low concentration of surfactant. Higher
      concentrations of surfactant downstream cause a Marangoni stress which
      decelerates the surface-an effect clearly shown by the velocity data. In the
      presence of 0.2 M salt, which significantly depresses the cmc, the adsorption of
      C(16)TAB is greatly reduced, probably because it forms cylindrical micelles,
      which diffuse much more slowly than free monomers. The apparatus is shown to be a
      very suitable platform for investigating surfactant adsorption and Marangoni
      flows under carefully controlled hydrodynamic conditions.

PMID- 12804911
TI  - Study of a mathematical model of metal ion complexes in solvent sublation.
AB  - Separation of metal ion complex, [(C(12)H(8)N(2))(3)Fe(2+)], with surfactant
      sodium dodecylphrate (DLS) complex from aqueous phase was carried out by solvent
      sublation, which obeys first-order kinetics. On the base of the complete
      transport mechanisms, the Langmuir adsorption, and the ion complex equilibrium in
      the aqueous phase, a mathematical model for the [(C(12)H(8)N(2))(3)Fe(2+)]
      surfactant ion complex is obtained with the aid of the Mathematic 4.0 program,
      4th Runge-Kutta method, and the Matlab programs. The effects of many parameters,
      such as K(a), K(l), K(ow), d(i), V(o), V(w), and Q(a), on solvent sublation are
      investigated. Furthermore, the simulation showed that the model is substantiated
      for experiments on the solvent sublation of the complex.

PMID- 12804912
TI  - Diffusion in an inhomogeneous system: NMR studies of diffusion in highly
      concentrated emulsions.
AB  - In this study the self-diffusion of different species in highly concentrated
      water-in-oil emulsions was investigated by means of the NMR diffusometry
      approach. The emulsions contained 96% aqueous solutions of salt or other
      additives; heptane was used as the oil phase. The surfactants, used to stabilize
      the emulsion, were soybean phosphatidylcholine and C(12)EO(4). The water drops
      were about 1.5 microm in diameter according to diffusion measurements performed
      on water. Diffusion of tetramethyl ammonium ions and glucose between the emulsion
      droplets was found to be negligible on the relevant time-scale (<1 s). On the
      contrary, acetic acid/acetate ions diffused between the droplets and had exchange
      times which were a function of pH.

PMID- 12804913
TI  - A thermodynamic analysis of the hydrogen ion titration of micelles.
AB  - A thermodynamic analysis of hydrogen ion titration is presented for association
      colloids with particular emphasis on surfactant micelles. When a particular type
      of the micellar Gibbs-Duhem relation (MGD), alpha(M)dmu(I)+(1-alpha(M))dmu(N)=0
      [alpha(M): the degree of ionization of micelles; mu(I),mu(N): chemical potentials
      of ionized and nonionized species], holds, the free energy change accompanying
      the ionization of the micelle G(ex) can be evaluated from the titration data in
      the same manner as for covalently bonded colloids such as linear polyions. In the
      case where the regular solution approximation is valid for mixed micelles, the
      titration curve should be a straight line with a slope yielding the interaction
      parameter, and G(ex) is given as a function of alpha(M)(2). For
      dodecyldimethylamine oxide micelles for which the MGD relation has been shown to
      hold, values of the calculated electrostatic free energy G(el) were close to but
      significantly greater than experimental G(ex) values when the former were
      calculated on the basis of the Poisson-Boltzmann equation for either a sphere or
      a plate with smeared charges in a salt solution of infinite volume. When the
      critical micelle concentration (cmc) data are combined with the hydrogen ion
      titration data, we obtain a criterion to judge whether the above MGD relation
      holds or not. When the MGD relation holds, the monomer concentration C(1) can be
      evaluated from the hydrogen ion titration. For most cases examined, the
      C(1)/C(1)(alpha(M)=0) from the titration agrees well with cmc/cmc(alpha(M)=0),
      suggesting cmc=C(1) above the cmc. For tetradecyldimethylamine oxide, the MGD
      relation does not hold in the range of low ionic strength and even at 0.1 M NaCl
      it has been found that C(1)/C(1)(alpha(M)=0)<cmc/cmc(alpha(M)=0), due probably to
      enormous micelle growth.

PMID- 12804914
TI  - Effective velocity and effective dispersion coefficient for finite-sized
      particles flowing in a uniform fracture.
AB  - In this work we derive expressions for the effective velocity and effective
      dispersion coefficient for finite-sized spherical particles with neutral buoyancy
      flowing within a water saturated fracture. We considered the miscible
      displacement of a fluid initially free of particles by another fluid containing
      particles of finite size in suspension within a fracture formed by two semi
      infinite parallel plates. Particle spreading occurs due to the combined actions
      of molecular diffusion and the dispersive effect of the Poiseuille velocity
      profile. Unlike Taylor dispersion, here the finite size of the particles is taken
      into account. It is shown that because the finite size of a particle excludes it
      from the slowest moving portion of the velocity profile, the effective particle
      velocity is increased, while the overall particle dispersion is reduced. A
      similar derivation applied to particles flowing in uniform tubes yields analogous
      results. The effective velocity and dispersion coefficient derived in this work
      for particle transport in fractures with uniform aperture are unique and ideally
      suited for use in particle tracking models.

PMID- 12804915
TI  - Viscous behavior of concentrated emulsions of two immiscible Newtonian fluids
      with interfacial tension.
AB  - A new equation for the relative viscosity of infinitely dilute emulsions of
      noncolloidal droplets is proposed using the analogy between shear modulus and
      shear viscosity. In the limit of capillary number -->0, the proposed equation
      reduces to the well-known Taylor viscosity law for infinitely dilute emulsions.
      Starting from the proposed equation for an infinitely dilute emulsion, new
      viscosity equations for concentrated emulsions are then developed using a
      differential scheme. The proposed equations for concentrated emulsions are
      evaluated in light of a large body of published experimental data on the
      viscosity of emulsions.

PMID- 12804916
TI  - Binding of poly(amido amine) dendrimer to sodium hyaluronate in aqueous NaCl
      solution.
AB  - Binding of poly(amido amine) dendrimer to sodium hyaluronate (NaHA) in aqueous
      0.25 M NaCl solution has been investigated by static light scattering. It was
      observed that the apparent weight-average molecular weight and the radius of
      gyration increase with the ratio of NH(2) terminal groups in the dendrimer to the
      carboxylate groups in the NaHA, [NH(2)]/[COO(-)]. Up to [NH(2)]/[COO(-)]=31, the
      observed variation of molecular weight was reproduced by the "average binding"
      model, where an average number of dendrimers binds to each NaHA chain. Based on
      the "critical binding" model, the maximum number, n(max), of dendrimers which can
      bind to a NaHA chain was calculated to be n(max)=300 for a solution of
      [NH(2)]/[COO(-)]=56. The obtained value corresponds to the binding of one
      dendrimer per 1.5 repeating units on a NaHA chain. It is suggested from the
      observed radius of gyration that, while the dendrimer-NaHA complexes of
      [NH(2)]/[COO(-)] up to 5 maintain a wormlike character similar to NaHA without
      bound dendrimers, those of [NH(2)]/[COO(-)] above 10 behave like rigid rods. It
      is concluded that the hydrogen-bonding interaction, besides the electrostatic
      interaction, should play an important role in the formation of the NaHA-dendrimer
      complexes.

PMID- 12804917
TI  - Association properties of ethylene oxide/styrene oxide diblock copolymer E17S8 in
      aqueous solution.
AB  - Ethylene oxide and styrene oxide were sequentially polymerized to form the
      diblock copolymer E(17)S(8) (E = oxyethylene, OCH(2)CH(2); S = oxyphenylethylene,
      OCH(2)CH(C(6)H(5)); subscripts denote number-average block lengths in repeat
      units). Light scattering was used to investigate the properties of the micelles
      formed in dilute solution in the temperature range 15-30 degrees C. The micelles
      are elongated (probably spheroidal) at the lower temperature and highly elongated
      (cylindrical, probably wormlike) at the higher temperature. Comparison with
      results reported for the copolymer E(11)B(8) (B = oxybutylene,
      OCH(2)CH(C(2)H(5))) allowed exploration of the effect of changing the hydrophobic
      block. The results provide useful indicators toward the design of ES copolymers
      with optimal solubilization properties.

PMID- 12804918
TI  - Concentration-dependent surface-enhanced resonance Raman scattering of a
      porphyrin derivative adsorbed on colloidal silver particles.
AB  - Surface-enhanced Raman spectra (SERS) of 5,10,15,20-tetrakis(1-decylpyridium-4
      yl)-21H,23H-porphintetrabromide or Por 10 (H(2)Tdpyp) adsorbed on silver
      hydrosols are compared with the FTIR and resonance Raman spectrum (RRS) in the
      bulk and in solution. Comparative analysis of the RR and the FTIR spectra
      indicate that the molecule, in its free state, has D(2h) symmetry rather than
      C(2v). The SERS spectra, obtained on adsorption of this molecule on borohydride
      reduced silver sol, indicate the formation of silver porphyrin. With the change
      in the adsorbate concentration, the SERS shows that the molecule changes its
      orientation on the colloidal silver surface. The appearance of longer wavelength
      band in the electronic absorption spectra of the sol has been attributed to the
      coagulation of colloidal silver particles in the sol. The long wavelength band is
      found to be red-shifted with the decrease in adsorbate concentration. The
      excitation profile study indicates that the resonance of the Raman excitation
      radiation with the original sol band is more important than that with the new
      aggregation band for the SERS activity. This indicates a large contribution of
      electromagnetic effect to surface enhancement.

PMID- 12804919
TI  - An approximate method for calculating depletion and structural interactions
      between colloidal particles.
AB  - An approximate method is evaluated for calculating the second virial coefficient
      in a dilute macromolecular solution bounded by two interfaces. The approximation
      is essentially the superposition of the coefficients calculated independently for
      each surface. To test this approach, the depletion interaction between two
      particles in a solution of nonadsorbing, spherical macromolecules is calculated
      in systems with either hard-wall or long-range electrostatic interactions. In all
      systems tested, the interparticle interaction energy calculated with the
      approximation is found to be in good agreement with that calculated using the
      exact approach (e.g., error less than 2% at the smallest separations). The
      primary advantage of this approximation is a significant reduction in the
      computation time required for calculating the depletion interaction, especially
      in charged systems. The paper also shows that the expressions for predicting the
      depletion interaction in purely hard-sphere systems can be used in dilute ionic
      systems, provided the appropriate effective macromolecule size is used. For the
      attractive depletion interaction, this effective size is determined by the range
      of the particle-macromolecule interaction (as opposed to the macromolecule
      macromolecule interaction).

PMID- 12804920
TI  - Electrophoretic mobility of a liquid drop in a salt-free medium.
AB  - A theory is proposed for the electrophoretic mobility mu of dilute spherical
      liquid drops of radius a in salt-free media containing only counterions (e.g.,
      nonaqueous media). As in the case of the electrophoretic mobility of rigid
      particle in salt-free media, there is a certain critical value of the drop
      surface charge separating two cases, that is, the low-surface-charge case and the
      high-surface-charge case. For the low-surface-charge case, mu coincides with that
      of a drop in an electrolyte solution in the limit of very low electrolyte
      concentrations kappaa-->0 (Huckel's limit), where kappa is the Debye-Huckel
      parameter. For the high-surface-charge case, however, mu becomes constant
      independent of the drop surface charge, since the counterion condensation takes
      place near the drop surface.

PMID- 12804921
TI  - On the limiting electrophoretic mobility of a highly charged colloidal particle
      in an electrolyte solution.
AB  - The electrophoretic mobility of a spherical charged colloidal particle in an
      electrolyte solution with large kappaa (where kappa= Debye-Huckel parameter and
      a= particle radius) tends to a nonzero constant value in the limit of high zeta
      potential. It is demonstrated that this is caused by the fact that counterions
      condensed near the highly charged particle surface do not contribute to the
      electrophoretic mobility and only co-ions govern the mobility. A simple method to
      derive the limiting electrophoretic mobility expression is given. The present
      method is also applied to cylindrical particles, showing that the leading term of
      the limiting electrophoretic mobility of a cylindrical particle in a transverse
      field with large kappaa is the same as that of a spherical particle. The
      electrophoretic mobility of a cylindrical particle in a tangential field, on the
      other hand, is proportional to the particle zeta potential and does not exhibit a
      constant limiting value for high zeta potentials.

PMID- 12804922
TI  - The ajmaline challenge in Brugada syndrome: a useful tool or misleading
      information?

PMID- 12804923
TI  - Clinical studies on coronary revascularization in patients with type 2 diabetes.
AB  - With the increasing prevalence, diabetes is rapidly growing into a global public
      health problem. Cardiovascular disease is a major consequence of this chronic
      condition, and a critical issue facing physicians worldwide today is choice of
      coronary revascularization procedures in treating these patients. Since the
      Bypass Angioplasty Revascularization Investigation (BARI) alert in 1995, there
      have been several reports on subgroup analysis of clinical trials and registries
      concerning revascularization among patients with diabetes. Although randomized
      control studies comparing percutaneous and surgical revascularization procedures
      in this high-risk group of patients are lacking, this article provides the
      background for the excess risk and reviews the findings of these investigations.
      Current strategies to improve outcomes in patients with diabetes undergoing
      coronary revascularization procedures are discussed.

PMID- 12804924
TI  - The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and
      recommended protocol.
AB  - AIMS: The diagnostic ECG pattern in Brugada syndrome (BS) can transiently
      normalize and may be unmasked by sodium channel blockers such as ajmaline.
      Proarrhythmic effects of the drug have been well documented in the literature. A
      detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been
      described. Therefore, we prospectively studied the risks of a standardized
      ajmaline test. METHODS AND RESULTS: During a period of 60 months, 158 patients
      underwent the ajmaline test in our institution. Ajmaline was given intravenously
      in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37
      patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the
      test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the
      drug challenge did not induce VT if the target dose, QRS prolongation >30%,
      presence/appearance of the typical ECG, or the occurrence of premature
      ventricular ectopy were considered as end points of the test. A positive response
      to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who
      underwent evaluation solely for syncope of unknown origin. CONCLUSION: The
      ajmaline challenge using a protocol with fractionated drug administration is a
      safe method to diagnose BS. Because of the potential induction of VT, it should
      be performed under continuous medical surveillance with advanced life-support
      facilities. Due to the prognostic importance all patients with aborted sudden
      death or unexplained syncope without demonstrable structural heart disease and
      family members of affected individuals should presently undergo drug testing for
      unmasking BS.

PMID- 12804925
TI  - QR in V1--an ECG sign associated with right ventricular strain and adverse
      clinical outcome in pulmonary embolism.
AB  - AIMS: To test the hypothesis that Qr in V(1)is a predictor of pulmonary embolism,
      right ventricular strain, and adverse clinical outcome. METHODS AND RESULTS:
      ECG's from 151 patients with suspected pulmonary embolism were blindly
      interpreted by two observers. Echocardiography, troponin I, and pro-brain
      natriuretic peptide levels were obtained in 75 patients with pulmonary embolism.
      Qr in V(1)(14 vs 0 in controls; p<0.0001) and ST elevation in V(1)> or =1 mV (15
      vs 1 in controls; p=0.0002) were more frequently present in patients with
      pulmonary embolism. Sensitivity and specificity of Qr in V(1)and T wave inversion
      in V(2)for predicting right ventricular dysfunction were 31/97% and 45/94%,
      respectively. Three of five patients who died in-hospital and 11 of 20 patients
      with a complicated course, presented with Qr in V(1). After adjustment for right
      ventricular strain including ECG, echocardiography, pro-brain natriuretic peptide
      and troponin I levels, Qr in V(1)(OR 8.7, 95%CI 1.4-56.7; p=0.02) remained an
      independent predictor of adverse outcome. CONCLUSIONS: Among the ECG signs seen
      in patients with acute pulmonary embolism, Qr in V(1)is closely related to the
      presence of right ventricular dysfunction, and is an independent predictor of
      adverse clinical outcome.

PMID- 12804926
TI  - The effect of a neuropeptide Y Y1 receptor antagonist in patients with angina
      pectoris.
AB  - AIMS: Neuropeptide Y (NPY) is a potent vasoconstrictor released during
      sympathetic activation that may be involved in myocardial ischaemia. We examined
      the effect of a Y1 receptor antagonist on haemodynamic and ischaemic responses to
      exercise in patients with coronary artery disease. METHODS AND RESULTS: Eighty
      two evaluable male patients were included in a randomized, double blind, two-way
      crossover study with a low dose (6.7 microg/kg/min; n=59)and a high dose (13.3
      microg/kg/min; n=23) of the Y1 receptor antagonist AR-H040922 given as infusions
      for 2h or placebo. Myocardial ischaemia during a symptom-limited exercise test
      was monitored by conventional ST-segment analysis and heart rate (HR)-adjusted ST
      changes including the ST/HR slope and ST/HR recovery. Administration of the high
      dose AR-H040922 attenuated systolic blood pressure by 6-11 mmHg (p<0.05) during
      and after exercise without affecting HR. None of the two doses of AR-H040922
      influenced any of the ischaemic parameters or duration of exercise, however. The
      maximal increase in NPY was higher during AR-H040922 (p<0.05) compared with
      placebo. CONCLUSIONS: Selective NPY Y1 receptor blockade attenuates the increase
      in blood pressure during exercise indicating a role for endogenous NPY in blood
      pressure regulation. Despite this effect, the Y1 receptor antagonist did not
      influence exercise-induced ischaemic parameters in patients with coronary artery
      disease.

PMID- 12804928
TI  - Impaired acute collateral recruitment as a possible mechanism for increased
      cardiac adverse events in patients with diabetes mellitus.
AB  - BACKGROUND: The mortality of coronary artery disease is increased in diabetic
      patients. An impaired collateral function is considered a possible explanation.
      This study should assess the influence of diabetes on collaterals by direct
      invasive assessment of collateral function. METHODS: In 90 consecutive patients
      with a chronic coronary occlusion (TCO) of >2 weeks duration a recanalization was
      done. Thirty patients with diabetes (33%) were compared with 60 (67%) without
      diabetes. Blood flow velocity and pressure were measured distal to the occlusion
      by intracoronary Doppler and pressure wires before PTCA, and again after PTCA
      during a final balloon reocclusion to assess acute recruitment of collaterals.
      Resistance indexes for collaterals (R(Coll)) and peripheral microcirculation
      (R(P)) were calculated. RESULTS: The R(Coll)(diabetics: 8.1+/-6.8 vs
      nondiabetics: 8.7+/-6.7 mmHg cm(-1)s(-1); p=0.68) and R(P)(5.6+/-4.2 vs 6.6+/-3.8
      mmHg cm(-1)s(-1); p=0.30) were similar in diabetic and nondiabetic patients
      before recanalization. During balloon reocclusion both R(Coll)and R(P)increased.
      This increase was significantly more pronounced in diabetic than in nondiabetic
      patients in TCOs <3 months duration. In TCOs of longer duration (> or =3 months)
      these differences were no longer detectable between both patient groups.
      CONCLUSIONS: Diabetic patients with TCOs have similarly developed collaterals as
      nondiabetic patients. However, in TCOs <3 months duration the acute recruitment
      of collaterals in case of reocclusion is impaired. This could explain some of the
      higher complication rate and mortality after coronary interventions in diabetic
      patients.

PMID- 12804927
TI  - Predictive value of basal C-reactive protein levels for myocardial salvage in
      patients with acute myocardial infarction is dependent on the type of reperfusion
      treatment.
AB  - AIMS: To evaluate whether C-reactive protein (CRP) levels on admission are
      predictive of myocardial salvage achieved with different reperfusion strategies
      in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Patients
      with AMI treated with stenting plus abciximab (n=125) and thrombolysis alone
      (n=54) or with abciximab (n=71) were prospectively studied. CRP levels were
      measured by a high sensitivity assay. The threshold of the upper quartile (12
      mg/l) was used to divide patients into two groups: 60 patients with high CRP (>12
      mg/l) and 190 patients with low CRP (< or =12 mg/l). Myocardial salvage was
      measured by technetium (Tc)-99(m)sestamibi scintigraphy. Patients in the high CRP
      group had a significantly lower salvage index (0.35+/-0.42 vs 0.48+/-0.34,
      p=0.01) and higher 18-month mortality (11.7 vs 3.2%, p=0.03) compared to those in
      the low CRP group. While basal CRP was not related to myocardial salvage in
      patients treated with stenting plus abciximab (p=0.89) or thrombolysis plus
      abciximab (p=0.43), a high CRP on admission was associated with a significantly
      lower salvage index (0.09+/-0.48 vs 0.42+/-0.37 in the low CRP group, p=0.006)
      among patients treated with thrombolysis alone. CONCLUSION: CRP levels on
      admission may predict the efficacy of reperfusion in patients with AMI. The
      predictive ability is dependent on the form of reperfusion therapy.

PMID- 12804929
TI  - The prevalence of heart failure and asymptomatic left ventricular systolic
      dysfunction in a typical regional pacemaker population.
AB  - AIMS: To assess the prevalence of heart failure and asymptomatic left ventricular
      systolic dysfunction in the chronically paced population. METHODS AND RESULTS:
      Three hundred and seven patients were identified from attendance at routine
      pacemaker follow-up clinic. Subjects underwent a medical history and examination,
      6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection
      fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26%
      NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with
      single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R),
      p<0.008), and those with chronic atrial fibrillation (AF) compared to those with
      sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of
      ischaemic heart disease and years of pacing were independently associated with
      the presence of heart failure (combined R=0.572, p<0.001). CONCLUSIONS: Heart
      failure due to left ventricular systolic dysfunction is common in the paced
      population. Only a minority of these had a pre-existing diagnosis and a smaller
      proportion were on 'optimal' therapy. Echocardiographic screening of this high
      risk population is justified to improve rates of diagnosis and treatment of heart
      failure.

PMID- 12804930
TI  - Clinical and economic impact of exercise electrocardiography and exercise
      echocardiography in clinical practice.
AB  - BACKGROUND: Patients with known or suspected coronary disease are often
      investigated to facilitate risk assessment. We sought to examine the cost
      effectiveness of strategies based on exercise echocardiography and exercise
      electrocardiography. METHODS AND RESULTS: We studied 7656 patients undergoing
      exercise testing; of whom half underwent exercise echocardiography. Risk was
      defined with the Duke treadmill score for those undergoing exercise
      electrocardiography alone, and by the extent of ischaemia by exercise
      echocardiography. Cox proportional hazards models, risk adjusted for pretest
      likelihood of coronary artery disease, were used to estimate time to cardiac
      death or myocardial infarction. Costs (including diagnostic and revascularisation
      procedures, hospitalisations, and events) were calculated, inflation-corrected to
      year 2000 using Medicare trust fund rates and discounted at a rate of 5%. A
      decision model was employed to assess the marginal cost effectiveness (cost/life
      year saved) of exercise echo compared with exercise electrocardiography. Exercise
      echocardiography identified more patients as low-risk (51% vs 24%, p<0.001), and
      fewer as intermediate- (27% vs 51%, p<0.001) and high-risk (22% vs 4%); survival
      was greater in low- and intermediate-risk and less in high-risk patients.
      Although initial procedural costs and revascularisation costs (in intermediate
      high risk patients) were greater, exercise echocardiography was associated with a
      greater incremental life expectancy (0.2 years) and a lower use of additional
      diagnostic procedures when compared with exercise electrocardiography (especially
      in lower risk patients). Using decision analysis, exercise echocardiography ( in
      2615/life year saved) was more cost effective than exercise electrocardiography.
      CONCLUSION: Exercise echocardiography may enhance cost-effectiveness for the
      detection and management of at risk patients with known or suspected coronary
      disease.

PMID- 12804931
TI  - Interventional cardiology in Europe 1999.
AB  - AIMS: The purpose of this registry is to collect data on trends in interventional
      cardiology within Europe. Special interest focuses on relative increases and
      ratios in newer revascularization approaches and its distribution in different
      regions in Europe. METHODS AND RESULTS: Questionnaires distributed to delegates
      of the national societies of cardiology represented in the European Society of
      Cardiology to be completed by local institutions and operators yielded that
      1,452,751 angiograms and 452,019 PTCAs were performed in 1999. This is an
      increase of 28% and 16%, respectively, compared with 1998. Most of these
      increases are due to high relative increases in eastern European countries. The
      number of PTCAs per 106 inhabitants rose to 714 in 1999. Coronary stenting
      increased by 31% to about 313,000 stents implanted in 1999. Complication rates
      remained stable, the need for emergency coronary artery bypass grafting showing a
      further slight decrease to currently 0.3%. CONCLUSION: Interventional cardiology
      in Europe is still growing, mainly due to rapid growth in countries with lower
      socio-economical levels. In some central European countries a saturation seemed
      to be reached with only minor increases in procedures performed. Coronary
      stenting remains the only noteworthy and growing complement or alternative to
      balloon angioplasty.

PMID- 12804932
TI  - The need for resources for clinical research: proceedings of a policy conference
      held at the European Heart House, 27-28 June 2002: executive summary.
AB  - The medical profession, in particular cardiologists, acknowledge the fact that
      during the last 30 years, much of the progress made in the field of medicine has
      resulted from fruitful and close collaboration between academia and the
      pharmaceutical industry. However, during the last decade, this relationship has
      changed considerably. The industry increasingly carries out its own research,
      development of drugs and trials, according to its own agenda. As a result,
      academia has lost its influence. This has led to a dramatic increase in the cost
      of clinical randomised trials. In the meantime, academic careers and research
      have become less attractive to physicians. Funding for research is increasingly
      devoted to basic science, in particular genomics, and little is left for clinical
      research. As a result, many important clinical trials in various areas of
      medicine, including cardiology, remain unfunded.

PMID- 12804934
TI  - Small bowel obstruction in an adolescent with pelvic inflammatory disease due to
      Chlamydia trachomatis.
AB  - A 19-yr-old adolescent, who was hospitalized because of pelvic inflammatory
      disease (PID) due to Chlamydia trachomatis, developed bile-stained emesis. A mild
      amount of free fluid in the pelvis was found on abdominal ultrasound but there
      was no sonographic evidence of a pelvic mass or of a tubo-ovarian abscess. Plain
      radiography and computer tomography (with contrast) of the abdomen revealed a
      high-grade partial small bowel obstruction. Conservative treatment, which
      included intravenous fluids and antibiotics together with continuous bowel
      decompression via nasogastric tube, led to resolution of the small bowel
      obstruction within 2 days and to resumption of oral feeding within 4 days of
      treatment. Follow-up for 6 months after this episode was uneventful. The present
      case calls for inclusion of plain radiography of the abdomen in the evaluation of
      PID associated with emesis. It also suggests that, in a clinically stable patient
      diagnosed with small bowel obstruction associated with PID, conservative
      treatment could be attempted before any operative intervention is considered.

PMID- 12804935
TI  - Impetigo herpetiformis unresponsive to therapy in a pregnant adolescent.
AB  - Impetigo herpetiformis is a rare pustular disorder affecting mainly pregnant
      women. We report a 16-yr-old adolescent primigravida, who presented with impetigo
      herpetiformis at 27 weeks gestation. She had a pustular erythroderma covering her
      entire body, except face, scalp, and palmoplantar regions, with severe pruritus
      and pain. After unsuccessful attempts of treatment with systemic corticosteroids,
      intravenous fluids, and antibiotics, treatment was switched to cyclosporine, but
      no therapeutic effect could be achieved. Because of the deteriorating condition
      of the patient, an early delivery decision was made. Her symptoms resolved after
      delivery, and at day 20 postpartum her skin lesions were completely resolved.

PMID- 12804936
TI  - Urinary tract infection and Chlamydia infection in adolescent females.
AB  - STUDY OBJECTIVE: To examine whether clinical or laboratory findings could
      distinguish Chlamydia trachomatis (CT) from urinary tract infection (UTI) among
      adolescent females in whom providers tested for both. DESIGN, SETTING,
      PARTICIPANTS: A laboratory database at an urban teen health center was reviewed
      to identify females who had both urine culture and ligase chain reaction (LCR)
      test for CT ordered at the same visit. History and physical findings were
      abstracted from the medical record. There were 81 visits with retrievable
      laboratory results and chart documentation. MAIN OUTCOME MEASURES: UTI was
      defined as >1000 colony-forming units on culture, and CT was defined as positive
      LCR test. Pearson's Chi-squared test was used to assess strength of the
      hypothesized associations. RESULTS: UTI was diagnosed in 20 (24%) and CT in 18
      (22%) of 82 visits. Concurrent CT was diagnosed in 6 of 20 subjects with UTI.
      Symptoms and physical signs did not differentiate UTI from CT. Positive urinary
      nitrites were associated with UTI, but did not exclude CT. Similarly, wet prep
      evidence of trichomonas or white blood cells was associated with CT, but did not
      exclude UTI. Clinical diagnosis of CT or UTI was 50% sensitive and 70% specific.
      CONCLUSIONS: Adolescent females who are screened for both CT and UTI have high
      rates of concurrent disease. Urinary or vaginal symptoms do not differentiate
      well between these infections. Clinical diagnosis is imprecise, suggesting that
      adolescent females with vaginal or urinary symptoms should be tested for both CT
      and UTI.

PMID- 12804938
TI  - Isolated clitoral hypertrophy.

PMID- 12804937
TI  - Vaginoscopic resection for rhabdomyosarcoma of the vagina: a case report and
      review of the literature.
AB  - Rhabdomyosarcoma is the most common soft-tissue sarcoma found in children.
      Genitourinary sites comprise 20% of the primary location of these tumors. A
      polypoid form of the embryonal type of rhabdomyosarcoma, sarcoma botyroides, is
      often found in girls under age 5. These tumors are usually localized to the
      anterior vaginal wall. Their superficial location and clinical symptoms lead to
      early diagnosis, and these tumors are therefore considered to be the easiest to
      treat and most likely to be cured. In the past 30 years we have seen a shift in
      treatment from radical surgery to conservative surgery with chemotherapy and
      radiation, with improved survival and preservation of normal anatomy and improved
      postoperative body imagery. Conservative excision in the past has been performed
      by sharp curettage of the anterior vaginal wall. We present a case of a 2-yr-old
      child with a RMS of the vagina for which we utilized vaginoscopy not only to
      determine the extent of the tumor but also for precise resection using a bipolar
      electrode with normal saline as the distension medium.

PMID- 12804939
TI  - Management quandry. HPV in teenagers.

PMID- 12804940
TI  - Genital injuries.

PMID- 12804941
TI  - Abnormal pap smears in adolescents.

PMID- 12804943
TI  - Pica when you least expect it.

PMID- 12804942
TI  - Cervical cytology screening and management of abnormal cytology in adolescent
      girls.

PMID- 12804977
TI  - Sturge-Weber-Klippel-Trenaunay syndrome: what's in a name?

PMID- 12804978
TI  - Chemokines and diseases.
AB  - Chemokines are a group of small, pro-inflammatory molecules first described for
      their pivotal role in the mobilization of specific leukocyte subsets towards
      sites of inflammation and their activation once they arrive. They have now
      emerged as key regulators in the development, differentiation and anatomic
      distribution of inflammatory cells. Chemokines also orchestrate both the innate
      immune response and antigen specific immunity through their coordination of
      dendritic cells and lymphocytes. Due to their vast functional responsibilities,
      they are linked to the pathogenesis of many seemingly unrelated diseases that
      include HIV infection, cancer, atherosclerosis, autoimmune diseases, graft
      rejection and dermatological disorders. This review focuses on the physiology of
      chemokines and their significant roles in the pathogenesis and progression of
      major diseases.

PMID- 12804979
TI  - Phacomatosis pigmentovasculosebacea: an unusual case of phacomatosis multiplex.
AB  - A 13-year-old Taiwanese boy had an unusual combination of nevus fuscocoeruleus,
      large cafe-au-lait macules, nevus achromicus, large telangiectatic nevi and
      systematized nevus sebaceus. The term "phacomatosis pigmentovasculosebacea" is
      proposed to describe the concurrence of these multiple nevi derived from
      pigmentary, vascular and epithelial cells.

PMID- 12804980
TI  - Fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva, a rare genetic disabling disease
      characterized by heterotopic bone formation, is of special interest for general
      medicine since the bone morphogenetic proteins (especially BMP-4) involved in its
      pathogenesis are known to play a role in skeletal morphogenesis, and the gene
      antagonist to BMP-4 noggin might be useful in preventing lamellar bone formation.
      We present two cases with characteristic musculo-skeletal abnormalities and
      histopathological features (inflammatory infiltrates which destroyed muscle
      tissue replacing it by proliferating fibroblasts). In one patient due to high
      activity of fibroblasts, the histopathologic pattern appeared to be atypical and
      the lesion was recognized by a general pathologist as sarcoma. The other patient,
      due to the symmetrical induration of sternocleidomastoid muscles, was primarily
      recognized as scleredema. We stress the diagnostic importance of skeletal
      abnormalities (hallux valgus and others), and discuss differentiation from
      progressive osseous heteroplasia (POH) and congenital or acquired localized
      cutaneous and muscle ossifications which have a much better prognosis, as well as
      Albright's hereditary osteodystrophy, which differs by the presence of various
      systemic abnormalities. A study of FOP might provide an important clue to the
      genetic molecular mechanism of bone formation, development of heterotopic bone
      and a possible prevention by molecular manipulation with the gene responsible for
      bone morphogenetic proteins and their antagonists.

PMID- 12804981
TI  - Klippel-Trenaunay syndrome and Sturge-Weber syndrome: variations on a theme?
AB  - We describe a patient with a complex neurocutaneous syndrome of congenital
      vascular malformations, abnormalities of brain and bones, and soft tissue
      hypertrophy of one leg. According to eponymous classification schemes, the
      patient can be assigned to two different clinical entities. Using the lethal gene
      theory it is possible to unify these different syndromes and to explain the
      overlap and diversity of these congenital vascular syndromes. We argue that it is
      better to describe such vascular malformation syndromes in
      anatomical/histological or functional terms and map the extent of the disease,
      rather than name it according to the eponymous classification.

PMID- 12804982
TI  - The sun protection factor (SPF) inadequately defines broad spectrum
      photoprotection: demonstration using skin reconstructed in vitro exposed to UVA,
      UVBor UV-solar simulated radiation.
AB  - Wavelength specific biological damage has been previously identified in human
      skin reconstructed in vitro. Sunburn cell and pyrimidine dimers were found after
      UVB exposure, and alterations of dermal fibroblasts after UVA exposure. These
      damages permitted us to discriminate UVB and UVA single absorbers. The present
      study shows that these biological effects can be obtained simultaneously by a
      combined UVB + UVA exposure using ultraviolet solar simulated light (UV-SSR),
      which represents a relevant UV source. In addition, the protection afforded by
      two broad spectrum sunscreen complex formulations was assessed after topical
      application. These two formulations displayed the same sun protection factor but
      different UVA protection factors determined by the persistent pigment darkening
      (PPD) method. Dose response experiments of UVA or UV-SSR showed that the
      preparation with the highest PF-UVA provided a better protection with regard to
      dermal damage compared to the other formulation. Using an original UVB source to
      obtain the UVB portion of SSR spectrum, the preparations provided the same
      protection. This study strikingly illustrates the fact that the photoprotection
      afforded by two sunscreen formulations having similar SPF values is not equal
      with regard to dermal damage related to photoaging.

PMID- 12804983
TI  - Immunohistochemical study of nerve fibres in basal cell carcinoma.
AB  - Few studies have been made about the influence of the autonomous nervous system
      on the proliferation of malignant cells. The aim of this work was to investigate
      if there is any relationship between the aggressiveness of basal cell carcinoma
      (BCC) and the presence of nerve fibres. We studied 20 samples of BCC, classified
      in two groups: non aggressive and aggressive, according to current criteria of
      malignancy. We used anti-neurofilament (NF) monoclonal antibody and anti-tyrosine
      hydroxylase (TH) polyclonal antibody, in order to make immunohistochemical
      detection of nerve fibres and adrenergic fibres respectively. We performed a semi
      quantitative score of the results. Our findings showed the existence of
      statistically significant differences between both groups studied. The largest
      number of nerve fibres were found in the less aggressive group, whereas they
      disappeared in infiltrating aggressive proliferations, independently of the
      histological pattern.

PMID- 12804984
TI  - Lack of upregulation of epidermal fatty acid binding protein in dithranol induced
      irritation.
AB  - The exact role of epidermal fatty acid binding protein (E-FABP) in skin is
      unknown. A restoration of the barrier function may be associated with an
      upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in
      response to oxidative stress. A recent observation that dithranol induced
      irritation is not associated with skin barrier impairment prompted us to
      investigate the expression of E-FABP in this skin condition to elucidate the
      unknown function of this protein in skin. This study shows lack of E-FABP
      upregulation after a single application of dithranol on uninvolved skin of
      patients with psoriasis. The expression of E-FABP in dithranol irritation
      correlates with the unimpaired skin barrier function as assessed by measurements
      of TEWL. Furthermore, we did not find evidence for the recently introduced
      hypothesis that E-FABP functions as an antioxidant protein in the skin irritation
      induced by dithranol as oxidative stressor.

PMID- 12804985
TI  - Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the
      treatment of Pyoderma gangrenosum associated with Crohn's disease.
AB  - Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's
      disease successfully treated with infliximab. The efficacy of this drug in many
      inflammatory diseases has already been reported, but its use in PG has only been
      seen in very few cases. Our study confirms that this therapy is a valid
      alternative solution for treating PG, which is often unresponsive to conventional
      therapies.

PMID- 12804986
TI  - Calcitriol ointment and clobetasol propionate cream: a new regimen for the
      treatment of plaque psoriasis.
AB  - For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile
      option: they can be used either alone or in combination with other agents such as
      topical corticosteroids. In this two-phase parallel-group study, the naturally
      occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D
      analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The
      proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with
      clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied
      in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g
      ointment applied in the evening, followed by monotherapy with either calcitriol
      or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations
      (global assessment of improvement, PASI and body surface area (BSA) affected)
      showed no significant differences between the two regimen groups at the primary
      endpoints (week 2 and week 12) or at any interim points. At week 2 the
      investigator's global assessment showed clinical success (psoriasis markedly
      improved, almost clear or clear) for more than 50% of the patients in both groups
      and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and
      calcipotriol regimen group at week 12. Least-square means analysis of PASI
      indicated the calcitriol regimen to be equivalent to the calcipotriol regimen.
      There were no significant differences between the two groups with regards to
      cutaneous safety or to incidence of adverse events. The present study shows that
      for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g
      ointment can provide a safe and effective alternative to calcipotriol 50 mug/g
      ointment while being administered within a regimen based on a bitherapy with
      corticosteroids followed by a vitamin D3 maintenance monotherapy.

PMID- 12804987
TI  - Successful use of preserved sclera of eyelid reconstruction.
AB  - Eyelid surgery involving resection of more than half the eyelid and formation of
      full-thickness defect requires not only reconstruction of the anterior lamella,
      but also reconstruction of the posterior lamella, including the tarsal plate and
      palpebral conjunctiva. However, no reconstruction methods are of complete
      satisfaction. We describe our successful experience with 5 cases of eyelid
      reconstruction using preserved sclera and a report of a typical case of them.
      Based on our 5 case experience and literature, we compared eyelid reconstruction
      using preserved sclera to reconstruction using nasal septal or auricular
      cartilage in terms of external appearance and functions of the eyelid. The
      outcomes for reconstruction using preserved sclera in all 5 of our patients have
      been favorable. Previous papers as to this method, even though small in number,
      also reported no functional and esthetic problems. This method is recommended for
      eyelid reconstruction due to the good results and its simplicity.

PMID- 12804988
TI  - Relapsing coalescent papular dermatosis of elderly patients: a precursor or an
      abortive lesion of Ofuji papuloerythroderma.
AB  - We describe a group of elderly patients (average: 71.1 year-old, 37 male and 6
      female patients) with relapsing, coalescent, papular dermatosis. The skin rash
      started as intensely pruritic, discrete, solid papules developing in crops in a
      fairly localized area. The primary papular lesions tended to coalesce into flat
      topped, polygonal papules or plaques that often showed a cobble stone-like
      appearance. The disease took a protracted course of repeated relapses without
      known precipitating factors. Both papular and coalescent plaque lesions showed
      compact perivascular infiltration of mononuclear cells containing varying
      populations of eosinophils in the upper dermis. Approximately half of the
      patients had mild hypereosinophilia and elevated serum IgE levels without
      histories of atopic diathesis. These clinicopathological features were consistent
      with those of the papular lesions that Ofuji originally defined as the primary
      skin rash of papuloerythroderma. We propose that our cases represent a precursor
      or an abortive lesion of Ofuji papuloerythroderma.

PMID- 12804989
TI  - Markers of metastasis in lip cancer.
AB  - The incidence of lip cancer in Granada, Spain, is much higher than that recorded
      in other countries. The natural history of the disease generally includes
      induction on previous actinic lesions, promotion with local growth of the tumour,
      and the appearance of metastasis in regional lymph node chains and,
      exceptionally, via the blood stream. In order to determine the risk factors for
      metastases, a retrospective hospital-based study was conducted of 251 cases of
      lower lip cancer diagnosed and treated during a 10-year period from 1985 to 1995.
      All patients studied had a minimum follow-up of five years. Among the metastasis
      risk factors considered, only localization in commissure showed statistical
      significance (p < 0.001).

PMID- 12804990
TI  - Epidemiologic determinants of herpes genitalis case detection rates among STD
      clinic attendees.
AB  - BACKGROUND AND OBJECTIVE: to report significant sociodemographic and behavioural
      outpatient characteristics in Greeks and foreign immigrants associated with the
      diagnosis of symptomatic herpes genitalis. METHODS: A cross sectional hospital
      based study (1990-96). RESULTS: In the context of an STD reference population (n
      = 5,831), herpes genitalis (n = 831) represents the second leading sexually
      transmitted disease (14.2%), more often affecting Greek outpatients. Immigrant
      women were found five times more infected than Greek. In Greek heterosexuals low
      partner change rate was the main characteristic at the moment of health seeking
      behaviour (median: 1 partner in the past six months). Homo/bisexual orientation
      in males resulted in lower detection rate. Injecting drug use history was not
      associated with an increased relative incidence. CONCLUSIONS: low risk behaviour
      in heterosexuals constitutes a background for further preventive interventions to
      reduce complications.

PMID- 12804991
TI  - Familial Sneddon's syndrome.
AB  - A syndrome associating Livedo Reticularis (LR) with Cerebrovascular disease (CVD)
      was described, in 1965, by Sneddon. It occurs sporadically, but a few familial
      cases of Sneddon's Syndrome (SS) have been reported, like these 3 cases that
      represent one of the largest number among siblings. We studied three male
      brothers, aged 28, 37 and 42 years, with CVD (ischaemic stroke in 2 patients and
      cerebral haemorrhages in the third) and their sister with no CVD. All patients
      presented with long lasting Livedo Reticularis, extending beyond the lower limbs.
      Skin biopsy on the centre of the reticular pattern showed, only in the second
      patient, partial endothelium detachment in dermo-hypodermic blood vessels. The
      males also had accesses of Livedoid Vasculitis (LV), in which a skin biopsy
      showed obliteration of several upper dermal vessels with hialin thrombi and a
      very scarce inflammatory infiltrate. Complementary studies, with an extensive
      investigation on pro-coagulation/pro-thrombotic features including
      antiphospholipid antibodies, were repeatedly negative. Their non-consanguineous
      parents were not affected, but among these kindred of 9 individuals, apart from
      the 4 patients reported above, LR and LV were present in two other brothers and
      also in an aunt and uncle, suggesting autosomal dominant pattern of inheritance,
      with incomplete penetrance. The relationship between Sneddon's Syndrome and
      Antiphospholipid Antibody Syndrome is controversial. The present cases, having
      repeatedly negative antiphospholipid antibodies, support the classification of
      Sneddon's Syndrome as an independent nosological entity.

PMID- 12804992
TI  - Difference between real and perceived power of dermoscopical methods for
      detection of malignant melanoma.
AB  - Clear proceedings in detection of malignant melanoma and monitoring of
      melanocytic nevi (MN) have been achieved by dermoscopy in recent years:
      sensitivity to 95% is possible for experts. Does patients' confidence in methods
      for detection of malignant melanoma   most important for adherence in follow-up  
      reflect this diagnostic power? A self-administered survey was performed in 210
      consecutive patients at 13 private dermatological practices and the department of
      Dermatology of the University of Regensburg. Confidence was assessed by a 5-step
      ordinal scale ranging from 1 to 5 (higher values indicate higher confidence) and
      willingness-to-pay (wtp) as health-economic instrument for naked-eye inspection
      (NEI), handheld dermoscopy (HHD), digital dermoscopy (DD), and teledermoscopy
      (TD); additional, wtp for a hypothetical method promising 100% accuracy. Data of
      143 patients (response rate 69.5%; mean age 37 years, 58% female) could be
      analysed. Mean confidence was 1.9   0.9 for NEI, 2.8   0.9 for HHD, 4.5   0.7 for
      DD, and 4.7   0.5 for TD. Mean wtp per examination was 0.64%   1.1 of monthly
      income for NEI, 1.1%   1.9 for HHD, 2.8%   3.3 for DD, 3.1%   4.6 for TD, and
      5.0%   7.8 for hypothetical method. Differences between methods were
      statistically significant. Compared to the hypothetical method, NEI achieved only
      14.9%, HHD 24.8%, DD 58.4%, and TD 60% of maximum confidence. This study was
      performed without any influence on routine information for patients. Results
      therefore represent patients' actual knowledge of dermoscopical methods in daily
      dermatological practices. Patients' confidence was highest for TD, HHD was
      clearly underestimated. Willingness-to-pay in HHD, DD, and TD was at least 40%
      below a hypothetical method promising 100% accuracy. Better information about
      diagnostic accuracy of methods available is necessary to increase patients'
      knowledge and confidence.

PMID- 12804993
TI  - Linear lupus erythematosus profundus on the scalp following the lines of
      Blaschko.
AB  - We describe a 10-year-old Japanese girl presenting linear alopecia on the scalp
      and forehead. Histological examination showed fat degeneration with mucin deposit
      and periappendageal infiltrate of mononuclear cells. We diagnosed her as having
      linear lupus erythematodes profundus with a linear configuration following the
      lines of Blaschko.

PMID- 12804994
TI  - Lipschutz genital ulceration: a rare manifestation of paratyphoid fever.
AB  - In 1913, a distinctive clinical entity of acute genital ulcer occurring in an
      adolescent girl with a non-venereal infectious aetiology was described by
      Lipschutz. Since the initial description, several aetiologies have been
      discussed, and among them, paratyphoid fever is very uncommon. After her return
      from a trip, a 25-year-old girl developed high fever and diarrhoea. Examination
      of the vulva revealed a genital ulcer. The rest of the general examination was
      normal. Blood cultures identified Salmonella paratyphi A, and a diagnosis of
      Lipschutz's ulcer associated with paratyphoid fever was made. Bacteriaemia was
      then treated with antibiotics and the vulvar ulceration rapidly disappeared.
      Lipschutz described a distinctive clinical entity of acute genital ulcers
      occurring in adolescents. To our knowledge, we report herein the second case
      associated with proved paratyphoid fever. The authors thus recommend that typhoid
      or paratyphoid fever should be included in the differential diagnosis of genital
      ulcerations.

PMID- 12804995
TI  - Cutaneous granulomas as the first manifestation of Hodgkin's disease.
AB  - We report the case of a 64-year-old male in whom fever, cutaneous rash and
      hepatomegaly were the first manifestations of Hodgkin disease (HD).
      Histologically a dense lymphohistiocytic infiltrate with a granulomatous pattern
      was found in the skin infiltrate. A computed tomography scan revealed
      hepatosplenomegaly and a small retroperitoneal lymphadenopathy. An hepatic
      percutaneous biopsy showed a granulomatous infiltration with typical Reed
      Sternberg cells. Cutaneous manifestations of HD are briefly reviewed. The authors
      underline that granulomatous infiltration of the skin as the first manifestation
      of lymphoma is a very rare feature. We also discuss the possible pathogenic
      mechanisms of skin granulomas.

PMID- 12804996
TI  - Porphyria cutanea tarda, dermatomyositis and non-Hodgkin lymphoma in virus C
      infection.
AB  - Virus C infection has been associated with a broad spectrum of extrahepatic
      diseases such as essential mixed cryoglobulinemia, membranous glomerulonephritis,
      vasculitis, rheumatoid arthritis and lupus erythematosus. The etiologic role of
      virus C has also been observed in some neoplasms such as non-Hodgkin's lymphoma
      and the monoclonal gammapathies. Many studies also support the link between this
      virus and porphyria cutanea tarda (PCT). Isolated cases suggest a relationship
      with dermatomyositis. Herein, we report the coexistence of PCT, non-Hodgkin's
      lymphoma and dermatomyositis in the same patient affected with virus C infection
      which has never previously been described.

PMID- 12804997
TI  - Chromomycosis due to Exophiala jeanselmei in a renal transplant recipient.
AB  - Chromomycosis is a rare mycotic infection that is more frequent in tropical and
      subtropical regions. Dematiaceous fungi are the causal agents of this mycosis.
      Several cases of chromomycosis in organ transplant recipients have been reported.
      We present a case of chromomycosis by Exophiala jeanselmei in a Spanish male who
      had received a renal transplant several months previously, and was receiving
      treatment with tacrolimus, prednisone and mycophenolate mofetil. Very few cases
      of chromomycosis due to Exophiala have been reported, and this is, to our
      knowledge, the first European case.

PMID- 12804998
TI  - Interstitial granulomatous dermatitis with plaques and arthritis.
AB  - Interstitial granulomatous dermatitis (IGD) is a histopathological disorder
      characterised by an infiltration of the reticular dermis with a predominance of
      interstitial and palisadic histiocytes with a few areas of degenerating collagen
      bundles associated with a variable number of polynuclear neutrophils and
      eosinophils. There are several clinical conditions with a pattern of IGD. The
      linear form associated with arthritis was the first variety described. There is
      also a second form, which presents with plaques. This variety may be associated
      with arthritis, use of certain drugs or the presence of different systemic
      disorders. We report a case of IGD with plaques and arthritis. We discuss the
      differential clinical and histological diagnosis with other inflammatory skin
      lesions, which may be associated with joint disorders and collagen degeneration.
      We believe that it should be considered in patients presenting with arthritis and
      skin lesions.

PMID- 12804999
TI  - Demodicidosis in a child with xantholeukaemia associated with type 1
      neurofibromatosis.
AB  - Although Demodex follicularum and Demodex brevis are common permanent
      ectoparasites of human pilosebaceous units, their incidence on children's skin is
      rare. We report a new case of demodicidosis in a 22-month-old girl undergoing
      chemotherapy for chronic myelomonocytic leukaemia associated with xanthoma and
      type 1 neurofibromatosis. The eruption cleared after oral and topical
      metronidazole therapy. Demodicidosis should be included in the differential
      diagnosis of facial eruption in immunosuppressed children.

PMID- 12805000
TI  - Acute generalized exanthematous pustulosis induced by terbinafine.
AB  - Terbinafine is an allylamine fungicidal agent that is widely used for the
      treatment of onychomycoses and other fungal infections. Adverse effects may occur
      in more than 10% of patients receiving oral terbinafine, with cutaneous reactions
      in 2.7%. We describe the development of acute generalized exanthematous
      pustulosis in a 36-year-old woman who took oral terbinafine.

PMID- 12805001
TI  - [Therapeutic drug monitoring of mycophenolate mofetil, sirolimus and cyclosporine
      at C2].
AB  - The evolutions in treatments and clinical practices in organ transplantations led
      to modifications in the therapeutic drug monitoring (TDM) of immunosuppressive
      drugs. A focus is made regarding the C2 sampling of cyclosporin, as well as the
      TDM of mycophenolate mofetil and sirolimus. A review of literature about the
      evolution of drug monitoring, technical methods and sampling strategies is
      described. Arguments in favour of TDM are thus a decrease in the frequency of
      both graft rejection and adverse drug reactions, however, new strategies or new
      targets are needed in new associations or indications.

PMID- 12805002
TI  - [From control of hematopoiesis to cellular therapy: the perspectives for
      transfusion].
AB  - The ability to identify, select and manipulate stem cells from tissues opens the
      way to regenerative medicine. In the field of hematopoiesis, our increasingly
      precise knowledge of the mechanisms of production and regulation of blood cells
      should permit in the near future the production of cells in sufficient quantity
      to be of interest for transfusion. Our present capacity to amplify hematopoietic
      stem cells and direct their differentiation towards the erythroid line is
      reviewed here. A procedure is described for the amplification of CD34 +
      hematopoietic stem cells of placental origin, based on the sequential use of
      specific combinations of growth factors in a given serum-free medium. Such
      conditions allowing the terminal maturation in vivo of large numbers of
      precursors produced ex vivo permit one to envisage important transfusion
      perspectives. A complementary source of red blood cells would in fact improve our
      transfusion capacity.

PMID- 12805003
TI  - [Judicial expertise in blood alcohol determination and toxicological analysis].
AB  - Blood alcohol determination or toxicological expert evaluation are a part of the
      judicial inquiry. They are devoted to authorized professionals registrated by the
      court of appeal and they are obliged to perform themselves the analysis. They
      bind the civil and penal liability of the professionals who are designated. After
      a reapparaisal of the French legislation concerning blood alcohol levels, the
      authors review the totality of problems resulting from the interpretation of
      results as well as the relationship to judicial authorities: expert nomination
      procedure, professional criterions, legal points, daily practice. Among usual
      questions from magistrates and policemen, the expert has to estimate the quantity
      of alcohol taken by an individual, evaluate the blood ethanol content of a
      subject when the blood collection is late, calculate blood ethanol from breath
      alcohol analysis. For forensic toxicology, professional criterions and legal
      aspects are also touched on.

PMID- 12805004
TI  - [Pheromones: an underestimated communication signal in humans].
AB  - The pheromones are molecules, mainly aliphatic acids, with or without perceptible
      odor, recognized by specific receptors, the stimulation of which induces
      neuroendocrine reactions and affects the individual behavior. Olfactory receptors
      are underexpressed in human, 70 % of genes have become nonfunctional pseudogenes.
      But the remaining function was tested and is able to induce emotional reactions
      corresponding to a non-verbal signal of social interactions. In the present
      study, we review the actual knowledge on the olfactory receptors. They belong to
      the G-protein-coupled-receptors. Their signal is transduced to the hypothalamic
      pituitary-gonadal axis. Some HLA-based olfactory cues are shown with reference to
      recent experiments. The pathophysiological hypotheses are considered with respect
      to studies in anorexia nervosa and Alzheimer' disease.

PMID- 12805006
TI  - [Peroxisome proliferator activated receptors PPARs: their role in carbohydrate
      and lipid metabolism].
AB  - Peroxisome proliferator activated receptors (PPAR) belong to a family of nuclear
      receptors broadly distributed in the organism. Their pleiotropic role has been
      recently proved as well as their pathogenic significance in diabetes, obesity,
      cell cycle controlling, carcinogenesis, inflammation and atherosclerosis. The
      three types of PPAR identified until today have different tissue localization.
      PPARgamma, primarily identified in macrophages and adipocytes, play an important
      role in the expression of proteins essential for lipid metabolism and
      adipogenesis. PPARalpha are localized predominantly in hepatocytes and have also
      an important role in lipid metabolism. PPAR are though to be lipid sensors in
      organism. Carbohydrate metabolism is also under the control of PPAR and their
      exogenous ligands, (ie: thiasolidinediones), are important antidiabetic drugs.

PMID- 12805005
TI  - [Real time PCR methodology for quantification of nucleic acids].
AB  - The polymerase chain reaction (PCR) has become an essential tool for molecular
      biologists and its introduction into nucleic acids detection systems has
      revolutionized the quantitative analysis of DNA and RNA. The technique has
      rapidly evolved over the last few years and the growing interest in quantitative
      applications of the PCR has favoured the development of real-time quantitative
      PCR. In this paper, we review, after presentation of the theorical aspects of
      PCR, the basic principles of real-time PCR with the introduction of the concept
      of threshold cycle. More precisely, we describe the novel assay formats that
      greatly simplify the protocols used for the detection of specific nucleic acids.
      We focus on the actual four technologies that enable sequence detection in a
      closed tube and that are SYBR Green I, TaqMan probes, Hybridization probes and
      Molecular Beacon probes. We then discuss the different quantification strategies
      in real time PCR and compare the competiting instruments on the market. The most
      important real-time PCR applications in clinical biology are also described.

PMID- 12805007
TI  - [A new, rapid and robust genotyping method for CYP2C9 and MDR1].
AB  - Single nucleotide polymorphisms (SNPs) can significantly affect human phenotypes.
      Detection of allelic variant carriers has become a major goal for clinical
      pharmacologists in order to study phenotype-genotype relationships. However,
      there is a crucial need for rapid, and validated pharmacogenetic tests. The aim
      of the study was to validate a new fluorescence PCR strategy for cytochrome P450
      2C9 (CYP2C9) and multidrug resistance gene (MDR1) genotyping. Results of CYP2C9
      and MDR1 genotypes determined with reference techniques were compared to those
      obtained by allelic discrimination assays employing fluorescent TaqMan  probes.
      Sixteen subjects carrying CYP2C9*2 and CYP2C9*3 allelic variants (heterozygous
      and homozygous) previously identified by sequencing and 55 subjects previously
      genotyped for MDR1 exon 26 (C3435T) SNP by conventional PCR-RFLP were genotyped
      with fluorescent PCR. Fluorescent PCR gave 100 % accuracy with the results
      obtained with reference genotyping strategies for each of the 3 SNPs. Genotyping
      results with fluorescent PCR repeated on three consecutive occasions remained
      constant over time for each of the 3 SNPs. Allelic discrimination assays based on
      fluorescent PCR gave entire satisfaction for CYP2C9 and MDR1 genotyping. This
      reliable genotyping strategy can be easily used in clinical practice and should
      be further developed for additional SNPs identification.

PMID- 12805008
TI  - [Quantitative antibody analysis: use for the diagnosis of hepatitis C virus
      chronic infection].
AB  - Hepatitis C virus (HCV) infection has been estimated in 600,000 subjects in
      France, with about 80 % of chronic infection. In the latter, anti-HCV antibodies
      and viral RNA are found together in patients blood. Today, only the use of
      polymerase chain reaction (PCR) technology allows the diagnosis of HCV chronic
      infection, confirmed by a positive PCR. However, PCR is a laborious and cost
      effective method. The aim of this study was to distinguish HCV chronic infection
      to past-infection or false reactivity only using the serology testing. Therefore,
      we looked for a correlation between the results of PCR, using the HCV Cobas
      Amplicor 2.0 assay, and the level of anti-HCV antibodies, assessed by the AxSYM
      HCV v.3.0 and expressed in signal/cutoff (s/co) ratio. We found using a panel of
      200 sera issued from 181 patients, a significant variation of s/co ratios between
      PCR positive and negative patients (respectively, 87.76 +/- 27.18 vs 10.13 +/-
      13.68 s/co, p < 0.0001), only in non treated or previously treated patients, non
      HIV coinfected, non renal transplanted or haemodialysis patients. An anti-HCV
      cutoff value at 34 s/co allows a predictive PCR results with 100 % sensitivity
      and 93.3 % specificity. Thus, for patients having a s/co equal or over 34, a
      positive PCR was found in 98.1 % of cases, allowing the diagnosis of HCV chronic
      infection (positive predictive value). Conversely, in patients with less than 34,
      HCV chronic infection can be excluded in 100 % of cases (negative predictive
      value). In conclusion, in most cases, the use of anti-HCV quantitative analysis
      in the AxSYM HCV v.3.0 assay could avoid PCR testing and facilitate the diagnosis
      of HCV chronic infection.

PMID- 12805009
TI  - [Coinfection with hepatitis C and B viruses with pre-C mutant].
AB  - We report on a case of co-infection VHB-VHC with a pre-core mutant, a rare
      association in the literature. The last consensus conference in march 2002 did
      not help us so much, since only VHC-VIH co-infection was considered. We report on
      our therapeutic experience about the treatment and discuss the recent studies
      aimed to define the function of respective virus in the case of co-infection. In
      the present case, the VHC infection has been completely cured, but some problems
      with the VHB infection are still unsolved.

PMID- 12805010
TI  - [Acute transverse myelitis: important role of biology in diagnosis].

PMID- 12805011
TI  - [Interference in the creatine kinase assay: the "wave" phenomenon].

PMID- 12805012
TI  - [Methemalbuminnemia after massive hemolysis during blackwater fever].
AB  - We report a case of blackwater fever with brown plasma due to the presence of
      methemalbumin. The discovery of plasma with this color is a rare event at the
      laboratory. This compound appears during intravascular hemolysis or hemorrhagic
      pancreatitis when the ability of haptoglobin and hemopexin to bind free
      hemoglobin has been exceeded. In these cases some of heme is oxidized to hematin
      and taken up by serum albumin to form an albumin-hematin complex called
      methemalbumin. The major clinical problem is to evoke the diagnosis of
      methemalbuminemia and not confuse with methemoglobinemia. In our case,
      methemalbumin was detected and quantified using a scanning spectrophotometer. Its
      diagnostic and clinicals consequences are discussed.

PMID- 12805013
TI  - [Relevance of anti-tissue transglutaminase antibodies in coeliac disease
      diagnosis].
AB  - Coeliac disease is precipitated upon exposure to the dietary wheat gluten.
      Definitive diagnosis relies on intestinal biopsy and regression of clinical and
      histological disorders with adherence to a gluten-free diet. Coeliac disease is
      usually associated with a malabsorption syndrome. However, both atypical and
      silent clinical forms have been recently described and prevalence of the disease
      may be under-estimated. Serological tests have been developed in order to select
      candidates for intestinal biopsy, but these biological parameters are not
      suitable for screening in the general population. Indeed, antigliadin IgG
      antibodies have a poor specificity. antigliadin IgA antibodies a poor
      sensitivity. The detection of antiendomysial IgA antibodies (EmA) by
      immunofluorescence, although considered as the "gold standard" of serological
      coeliac disease markers, could not be automated, depends on a subjective
      fluorescence display, and may be limited by the degree of training of the
      observer. In year 1997, tissue transglutaminase (tTg) has been identified as the
      main autoantigen recognized by EmA. On this basis, solid-phase enzyme-linked
      immunosorbent assays (Elisa) have been developed in order to potentially replace
      the EmA assay. Several commercial kits are now available but their diagnostic
      performances have not yet been compared. We selected 75 sera, including sera from
      26 patients with coeliac disease in order to evaluate five commercial anti-tTG
      Elisa kits. For all patients, treated or not, detection of anti-tTG antibodies
      with four of the five tested kits correlates with EmA test. Kits using human tTG
      have the highest specificity, equivalent to the value of EMA test, and widely
      better than antigliadin antibodies. Anti-tTG Elisa kits using human tTG may be
      used as an alternative way to the EmA assay in the next future, and may supplant
      IgA anti-gliadin antibodies for coeliac disease screening.

PMID- 12805014
TI  - [Point care testing in blood gas and electrolyte analysis : examples of
      implementation and cost analysis].
AB  - An increasing proportion of laboratories manage and organize point of care
      testing (POCT). The purpose of this article is to describe the implementation
      made at Lariboisiere hospital for three remote blood gas analysers. The most
      important aspect in this achievement is the comprehensive computerization, making
      possible real time management of POCT in agreement with the Point of Care unit
      Management team. In addition, we present a running cost analysis, comparing three
      Blood gas systems (Rapidlab860, Rapidpoint 400--Bayer Diagnostics and i-Stat
      Abbott Diagnostics). This study indicates that cost per test hugely varies based
      on the daily sample demand. In addition to analytical and organizational items,
      the clinical chemist should consider the testing demand as a key factor in
      choosing an analyser for POCT.

PMID- 12805015
TI  - [Acute myeloblastic leukemia without maturation (AML-M1) with basophilic elements
      and associated with translocation t(6;9)].
AB  - The clinical, hematological, and cytogenetic data from a 4 year-old child with
      acute myeloid (AML-M1) and basophilia is reported. Interestingly, cytogenetic
      investigations revealed the presence of the translocation t(6;9) (p23;q34). This
      abnormality is rare and associated with myelodysplastic syndromes or with
      subtypes of acute myeloid leukemia (M1, M2, M4, M7), usually with preceding or
      underlying myelodysplasia. The prognosis is poor, without response to
      chemotherapy regimen alone. Allogeneic bone marrow transplantation appears likely
      to be a more appropriate treatment.

PMID- 12805016
TI  - Beta-adrenergic and antiadrenergic modulation of cardiac adenylyl cyclase is
      influenced by phosphorylation.
AB  - Adenosine protects the myocardium of the heart by exerting an antiadrenergic
      action via the adenosine A1 receptor (A1R). Because beta 1-adrenergic receptor
      (beta 1R) stimulation elicits myocardial protein phosphorylation, the present
      study investigated whether protein kinase A (PKA) catalyzed rat heart ventricular
      membrane phosphorylation affects the beta 1R adrenergic and A1R adenosinergic
      actions on adenylyl cyclase activity. Membranes were either phosphorylated with
      PKA in the absence/presence of a protein kinase inhibitor (PKI) or
      dephosphorylated with alkaline phosphatase (AP) and assayed for adenylyl cyclase
      activity (AC) in the presence of the beta 1R agonist isoproterenol (ISO) and/or
      the A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA). 32P incorporation into
      the protein substrates of 140-120, 43, and 29 kDa with PKA increased both the ISO
      elicited activation of AC by 51-54% and the A1R-mediated reduction of the ISO
      induced increase in AC by 29-50%, thereby yielding a total antiadrenergic effect
      of approximately 78%. These effects of PKA were prevented by PKI. AP reduced the
      ISO-induced increase in AC and eliminated the antiadrenergic effect of CCPA.
      Immunoprecipitation of the solubilized membrane adenylyl cyclase with the use of
      a polyclonal adenylyl cyclase VI antibody indicated that the enzyme is
      phosphorylated by PKA. These results indicate that the cardioprotective effect of
      adenosine afforded by its antiadrenergic action is facilitated by cardiac
      membrane phosphorylation.

PMID- 12805017
TI  - Cyclical mechanical stretch-induced apoptosis in myocytes from young rats but
      necrosis in myocytes from old rats.
AB  - Mechanical load as stimulus for apoptosis and necrosis could be responsible for
      the loss of cardiomyocytes. Ventricular myocytes from young (3 mo) and old (14-24
      mo) rats underwent cyclical mechanical stretch (CMS; 5% elongation, 1 Hz) for 24
      h. Spontaneous apoptosis was in myocytes from young rats 0.33 +/- 0.12% and from
      old rats 1.05 +/- 0.35% [Tdt-mediated dUTP nick-end labeling (TUNEL) assay];
      associated with a decrease of Bcl-2. CMS increased the apoptosis to 0.58 +/-
      0.18% in myocytes from young rats. Western blot analysis showed that CMS reduced
      Bcl-2 and increased p53 (young rats). Bax was not changed by CMS. These were
      confirmed by cytochrome c release (31 +/- 13%) and by the enrichment of cytosolic
      nucleosomes (11 +/- 8%). CMS did not influence the apoptosis in myocytes from old
      rats (TUNEL assay, Bcl-2, Bax, or p53). CMS did not cause necrosis in myocytes
      from young rats. CMS increased the number of necrotic cells by showing the cell
      membrane rupture in myocytes from old rats (50 +/- 13% 5
      hexadecanoylaminofluorescein-positive and 38 +/- 6% propidium iodide-positive
      cells) as well as by measuring the lactate dehydrogenase release. The results
      suggest that CMS-induced apoptosis in myocytes of young rats but necrosis in
      myocytes from old rats, which could be attributed to more stress sensitivity of
      cells from old rats.

PMID- 12805018
TI  - Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes
      and subsequently induces cell death.
AB  - Type II secretory phospholipase A2 (sPLA2) is a cardiovascular risk factor. We
      recently found depositions of sPLA2 in the necrotic center of infarcted human
      myocardium and normally appearing cardiomyocytes adjacent to the border zone. The
      consequences of binding of sPLA2 to ischemic cardiomyocytes are not known. To
      explore a potential effect of sPLA2 on ischemic cardiomyocytes at a cellular
      level we used an in vitro model. The cardiomyocyte cell line H9c2 or adult
      cardiomyocytes were isolated from rabbits that were incubated with sPLA2 in the
      presence of metabolic inhibitors to mimic ischemia-reperfusion conditions. Cell
      viability was established with the use of annexin V and propidium iodide or 7
      aminoactinomycin D. Metabolic inhibition induced an increase of the number of
      flip-flopped cells, including a population that did not stain with propidium
      iodide and that was caspase-3 negative. sPLA2 bound to the flip-flopped cells,
      including those negative for caspase-3. sPLA2 binding induced cell death in these
      latter cells. In addition, sPLA2 potentiated the binding of C-reactive protein
      (CRP) to these cells. We conclude that by binding to flip-flopped cardiomyocytes,
      including those that are caspase-3 negative and presumably reversibly injured,
      sPLA2 may induce cell death and tag these cells with CRP.

PMID- 12805019
TI  - Calcium sparks in mouse ventricular myocytes at physiological temperature.
AB  - In cardiac muscle, Ca2+ is released from the sarcoplasmic reticulum (SR) in units
      called Ca2+ sparks. Ca2+ spark characteristics have been studied almost entirely
      at room temperature. This study compares characteristics of spontaneous sparks
      detected with fluo 3 in resting mouse ventricular myocytes at 22 and 37 degrees
      C. The incidence and frequency of Ca2+ sparks decreased dramatically at 37
      degrees C compared with 22 degrees C. Also, spark amplitudes and times to peak
      were significantly reduced at 37 degrees C. In contrast, spatial width and decay
      times were unchanged. During field stimulation, peak spatially averaged
      transients were similar at 22 and 37 degrees C, and experiments with fura 2
      demonstrated that diastolic and systolic Ca2+ concentrations were unchanged.
      However, SR Ca2+ content decreased significantly at 37 degrees C. Restoration of
      SR Ca2+ by superfusion with 5 mM Ca2+ increased spark frequency but did not
      reverse the effects of temperature on spark parameters. Thus effects of
      temperature on spark frequency may reflect changes in SR stores, whereas changes
      in spark amplitude and rise time may reflect known effects of temperature on
      ryanodine receptor function.

PMID- 12805020
TI  - Intraluminal pressure stimulates MAPK phosphorylation in arterioles: temporal
      dissociation from myogenic contractile response.
AB  - Members of the MAPK family of enzymes, p42/44 and p38, have been implicated in
      both the regulation of contractile function and growth responses in vascular
      smooth muscle. We determined whether such kinases are activated during the
      arteriolar myogenic response after increases in intraluminal pressure. Particular
      emphasis was placed on temporal aspects of activation to determine whether such
      phosphorylation events parallel the known time course for myogenic contraction.
      Experiments used single cannulated arterioles isolated from the cremaster muscle
      of rats with some vessels loaded with the fluorescent Ca2+-sensitive dye fura 2
      (2 microM). The p42/44 inhibitor PD-98059 (50 microM) caused vasodilation but did
      not prevent pressure-induced myogenic constriction. The vasodilator response was
      accompanied by decreased smooth muscle intracellular Ca2+. Western blotting
      revealed a significant increase in the level of phosphorylation of p42/44 15 min
      after the application of a 30- to 100-mmHg pressure step. Phosphorylation of
      p42/44 was a late event that appeared to be temporally dissociated from
      contraction, which was complete within 1-5 min. EGF (80 nM) caused marked
      phosphorylation of p42/44 but only acted as a weak vasoconstrictor. The p38
      inhibitor SB-203580 (10 microM) did not alter baseline diameter, nor did it
      prevent myogenic vasoconstriction. Consistent with these observations, SB-203580
      did not cause a measurable change in intracellular Ca2+. The results demonstrate
      activation of the p42/44 class of MAPK resulting from increased transmural
      pressure. Such activation is, however, dissociated from the acute pressure
      induced vasoconstrictor response in terms of time course and may represent the
      activation of compensatory, but parallel, pathways, including those related to
      growth and remodeling.

PMID- 12805021
TI  - Developmental changes in left and right ventricular diastolic filling patterns in
      mice.
AB  - Developmental changes in left and right ventricular diastolic filling patterns
      were determined noninvasively in isoflurane-anesthetized outbred ICR mice. Blood
      velocities in the mitral and tricuspid orifices were recorded in 16 embryos at
      days 14.5 (E14.5) and 17.5 of gestation (E17.5) using an ultrasound biomicroscope
      and also serially in three groups of postnatal mice aged 1-7 days (n = 23), 1-4
      wk (n = 18), and 4-12 wk (n = 27) using 20-MHz pulsed Doppler. Postnatal body
      weight increased rapidly to 8 wk. Heart rate increased rapidly from approximately
      180 beats/min at E14.5 to approximately 380 beats/min at 1 wk after birth and
      then more gradually to plateau at approximately 450 beats/min after 4 wk.
      Ventricular filling was quantified using the ratio of peak velocity of early
      ventricular filling due to active relaxation (E wave) to that of the late
      ventricular filling caused by atrial contraction (A wave) (peak E/A ratio) and
      the ratio of the peak E velocity to total time-velocity integral of E and A waves
      (peak E/total TVI ratio). Both ventricles had similar diastolic filling patterns
      in embryos (peak E/A ratio of 0.28 +/- 0.02 for mitral flow and 0.27 +/- 0.02 for
      tricuspid flow at E14.5). After birth, mitral peak E/A increased to >1 between
      the third and fifth day, continued to increase to 2.25 +/- 0.25 at approximately
      3 wk, and then remained stable. The tricuspid peak E/A ratio increased much less
      but stabilized at the same age (increased to 0.79 +/- 0.03 at 3 wk). The peak
      E/total TVI ratio showed similar left-right differences and changes with
      development. Age-related changes were largely due to increases in peak E
      velocity. The results suggest that diastolic function matures approximately 3 wk
      postnatally, presumably in association with maturation of ventricular recoil and
      relaxation mechanisms.

PMID- 12805022
TI  - Role of endothelial intermediate conductance KCa channels in cerebral EDHF
      mediated dilations.
AB  - The present study evaluated the role of endothelial intermediate conductance
      calcium-sensitive potassium channels (IKCa) in the mechanism of endothelium
      derived hyperpolarizing factor (EDHF)-mediated dilations in pressurized cerebral
      arteries. Male rat middle cerebral arteries (MCA) were mounted in an isolated
      vessel chamber, pressurized (85 mmHg), and luminally perfused (100 microl/min).
      Artery diameter was measured simultaneously with either endothelial intracellular
      Ca2+ concentration ([Ca2+]i; fura-2) or changes in endothelial membrane potential
      [4-[2-[6-(dioctylamino)-2-naphthalenyl]ethenyl]1-(3-sulfopropyl)-pyridinium (di-8
      ANEPPS)]. Nitric oxide synthase and cyclooxygenase inhibitors were present
      throughout. Luminal application of UTP produced EDHF-mediated dilations that
      correlated with significant endothelial hyperpolarization. The dilation and
      endothelial hyperpolarization were virtually abolished by inhibitors of IKCa
      channels but not by selective inhibitors of small or large conductance KCa
      channels (apamin and iberiotoxin, respectively). Additionally, direct stimulation
      of endothelial IKCa channels with 1-ethyl-2-benzimidazolinone (1-EBIO) produced
      endothelial hyperpolarization and vasodilatation that were blocked by inhibitors
      of IKCa channels. 1-EBIO hyperpolarized the endothelium but did not affect
      endothelial [Ca2+]i. We conclude that the mechanism of EDHF-mediated dilations in
      cerebral arteries requires stimulation of endothelial IKCa channels to promote
      endothelial hyperpolarization and subsequent vasodilatation.

PMID- 12805023
TI  - Inflammatory stress increases receptor for lysophosphatidylcholine in human
      microvascular endothelial cells.
AB  - The atherogenic serum lysophosphatidylcholine (LPC) is known to mediate vascular
      endothelial responses ranging from upregulation of adhesion molecules and growth
      factors to secretion of chemokines and superoxide anion. We investigated whether
      endothelial cells express receptors for LPC, which may account for their actions.
      Human brain microvascular (HBMEC) and dermal microvascular endothelial cells
      (HMEC) were prepared for RT-PCR analysis for possible expression of the G protein
      coupled receptors, GPR4 and G2A, which are believed to be specific LPC receptors.
      Results indicated that HBMEC expressed low basal GPR4 mRNA, but stimulation with
      tumor necrosis factor-alpha (TNF-alpha) (100 U/ml) or H2O2 (50 micromol/l) for 2
      h or overnight upregulated expression severalfold. In contrast, HMEC expressed
      high basal GPR4 mRNA, which was not further increased by either TNF-alpha or H2O2
      stimulation. Another LPC receptor, G2A, was not detected in either endothelial
      cell type. Competition binding studies were made to evaluate specific binding of
      [3H]LPC to the intact endothelial cell monolayer. Basal specific [3H]LPC binding
      in HBMEC was approximately eight times lower than in HMEC; however, TNF-alpha or
      H2O2 stimulation increased [3H]LPC binding on HMBEC but not HMEC. The results
      indicated that GPR4 expression was consistent with specific [3H]LPC binding.
      Overall, we report that endothelial cells selectively expressed GPR4, a specific
      LPC receptor. Furthermore, GPR4 expression by HBMEC, but not HMEC, was increased
      by inflammatory stresses. We conclude that endogenous GPR4 in endothelial cells
      may be a potential G protein-coupled receptor by which LPC signals
      proinflammatory activities.

PMID- 12805024
TI  - Targeted O2 delivery by low-P50 hemoglobin: a new basis for O2 therapeutics.
AB  - To assess O2 delivery to tissue by a new surface-modified, polyethylene glycol
      conjugated human hemoglobin [MP4; Po2 at 50% saturation of hemoglobin (P50); 5.4
      mmHg], we studied microcirculatory hemodynamics and O2 release in golden Syrian
      hamsters hemodiluted with MP4 or polymerized bovine hemoglobin (PolyBvHb; P50
      54.2 mmHg). Comparisons were made with the animals' hemodiluted blood with a non
      O2 carrying plasma expander with similar solution properties (Dextran-70).
      Systemic hemodynamics (arterial blood pressure and heart rate) and acid-base
      parameters were not correlated with microhemodynamics (arteriolar and venular
      diameter, red blood cell velocity, and flow). Microscopic measurements of Po2 and
      the O2 equilibrium curves permitted analysis of O2 release in precapillary and
      capillary vessels by red blood cells and plasma hemoglobin separately. No
      significant differences between the groups of animals with respect to arteriolar
      diameter, flow, or flow velocity were observed, but the functional capillary
      density was significantly higher in the MP4-treated animals (67%) compared with
      PolyBvHb-treated animals (37%; P < 0.05) or dextran-treated animals (53%). In the
      PolyBvHb-treated animals, predominant O2 release (both red blood cells and plasma
      hemoglobin) occurred in precapillary vessels, whereas in MP4 animals most of the
      O2 was released from both red blood cells and plasma hemoglobin in capillaries.
      Base excess correlated directly with capillary O2 release but not systemic O2
      content or total O2 release. Higher O2 extraction of both red blood cell and
      plasma hemoglobin in capillaries represents a new mechanism of action of cell
      free hemoglobin. High O2 affinity appears to be an important property for cell
      free hemoglobin solutions.

PMID- 12805025
TI  - Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after
      ischemia and reperfusion.
AB  - Adrenomedullin (AM) has been shown to protect against cardiac remodeling. In this
      study, we investigated the potential role of AM in myocardial ischemia
      reperfusion (I/R) injury through adenovirus-mediated gene delivery. One week
      after AM gene delivery, rats were subjected to 30-min coronary occlusion,
      followed by 2-h reperfusion. AM gene transfer significantly reduced the ratio of
      infarct size to ischemic area at risk and the occurrence of sustained ventricular
      fibrillation compared with control rats. AM gene delivery also attenuated
      apoptosis, assessed by both terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling assay and DNA laddering. The effect of AM gene transfer on
      infarct size, arrhythmia, and apoptosis was abolished by an AM antagonist,
      calcitonin gene-related peptide [CGRP(8-37)]. Expression of human AM
      significantly increased cardiac cGMP levels and reduced superoxide production,
      superoxide density, NAD(P)H oxidase activity, p38 MAPK activation, and Bax
      levels. Moreover, AM increased Akt and Bad phosphorylation and Bcl-2 levels, but
      decreased caspase-3 activation. These results indicate that AM protects against
      myocardial infarction, arrhythmia, and apoptosis in I/R injury via suppression of
      oxidative stress-induced Bax and p38 MAPK phosphorylation and activation of the
      Akt-Bad-Bcl-2 signaling pathway. Successful application of this technology may
      have a protective effect in coronary artery diseases.

PMID- 12805026
TI  - Superoxide-NO interaction decreases flow- and agonist-induced dilations of
      coronary arterioles in Type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2-DM) markedly increases the incidence of ischemic
      heart disease (IHD) and, consequently, mortality. However, the underlying
      mechanisms leading to IHD in T2-DM are not completely understood. We hypothesized
      that in T2-DM the regulation of coronary microvascular resistance by local
      mechanisms is altered. Thus, in coronary arterioles (diameter: approximately 80
      microm) isolated from male mice with T2-DM (C57BL/KsJ-db/db) and control
      littermates, responses to changes in intraluminal pressure, flow, and agonists
      with known mechanisms of action were studied. Increases in pressure (from 20 to
      120 mmHg) resulted in similar myogenic responses of coronary arterioles of
      control and db/db mice, whereas dilations in response to cumulative
      concentrations of ACh and the nitric oxide (NO) donor NONOate were significantly
      decreased compared with those of control vessels. On the other hand, responses to
      adenosine were not different between vessels of control and db/db mice. Increases
      in flow (0-20 microl/min) resulted in dilations of control vessels (maximum: 38
      +/- 4%) that were inhibited by the NO synthase inhibitor N omega-nitro-L-arginine
      methyl ester (L-NAME). In contrast, arterioles of db/db mice exhibited greatly
      reduced dilations to flow (maximum: 4 +/- 6%) that were unaffected by L-NAME. In
      carotid arteries of db/db mice, superoxide dismutase (SOD)-sensitive, enhanced
      superoxide production was detected by dihydroethydine staining and lucigenin
      enhanced chemiluminescence. Correspondingly, intraluminal administration of SOD
      significantly augmented flow-, ACh-, and NONOate-induced dilations of diabetic
      arterioles, and then flow- and ACh-induced responses could be inhibited by L
      NAME. Collectively, these findings suggest that in T2-DM, due to an enhanced
      superoxide production, NO mediation of agonist- and flow-induced dilations of
      coronary arterioles is reduced. This alteration in the regulation of coronary
      microvascular resistance may contribute to the development of IHD in T2-DM.

PMID- 12805027
TI  - Early autonomic malfunction in normotensive individuals with a genetic
      predisposition to essential hypertension.
AB  - One of the primary pathologies associated with hypertension is a complex
      autonomic dysfunction with evidence of sympathetic hyperactivity and/or vagal
      withdrawal. We investigated the possibility for early detection of essential
      hypertension on the basis of the analysis of heart rate (HR) and blood pressure
      fluctuations, which reflect autonomic control. Young adult normotensive offspring
      of one hypertensive parent (KHT; n = 12) and normotensive offspring of two
      normotensive parents (YN; n = 14) participated in this study. ECG, continuous
      blood pressure, and respiration were recorded during steady-state conditions and
      under various autonomic challenges. Time-frequency decomposition of these signals
      was performed with the use of a continuous wavelet transform. The use of the
      wavelet transform enables the extension of typical HR variability analysis to non
      steady-state conditions. This time-dependent spectral analysis of HR allows time
      dependent quantification of different spectral components reflecting the
      sympathetic and parasympathetic activity during rapid transitions, such as an
      active change in posture (CP). During an active CP from the supine to standing
      position, KHT demonstrated a significantly greater increase in the low-frequency
      fluctuations in HR than YN, indicating enhanced sympathetic involvement in the HR
      response to CP, and a reduced alpha-index, indicating decreased baroreceptor
      sensitivity. On recovery from handgrip, vagal reactivation was more sluggish in
      KHT. These results indicate the early existence of malfunctions in both branches
      of autonomic control in individuals at increased risk of hypertension.

PMID- 12805028
TI  - Downregulation of profilin with antisense oligodeoxynucleotides inhibits force
      development during stimulation of smooth muscle.
AB  - The actin-regulatory protein profilin has been shown to regulate the actin
      cytoskeleton and the motility of nonmuscle cells. To test the hypothesis that
      profilin plays a role in regulating smooth muscle contraction, profilin antisense
      or sense oligodeoxynucleotides were introduced into the canine carotid smooth
      muscle by a method of reversible permeabilization, and these strips were
      incubated for 2 days for protein downregulation. The treatment of smooth muscle
      strips with profilin antisense oligodeoxynucleotides inhibited the expression of
      profilin; it did not influence the expression of actin, myosin heavy chain, and
      metavinculin/vinculin. Profilin sense did not affect the expression of these
      proteins in smooth muscle tissues. Force generation in response to stimulation
      with norepinephrine or KCl was significantly lower in profilin antisense-treated
      muscle strips than in profilin sense-treated strips or in muscle strips not
      treated with oligodeoxynucleotides. The depletion of profilin did not attenuate
      increases in phosphorylation of the 20-kDa regulatory light chain of myosin
      (MLC20) in response to stimulation with norepinephrine or KCl. The increase in F
      actin/G-actin ratio during contractile stimulation was significantly inhibited in
      profilin-deficient smooth muscle strips. These results suggest that profilin is a
      necessary molecule of signaling cascades that regulate carotid smooth muscle
      contraction, but that it does not modulate MLC20 phosphorylation during
      contractile stimulation. Profilin may play a role in the regulation of actin
      polymerization or organization in response to contractile stimulation of smooth
      muscle.

PMID- 12805029
TI  - Microvascular oxygen distribution in awake hamster window chamber model during
      hyperoxia.
AB  - The microvascular effects and hemodynamic events following exposure to normobaric
      hyperoxia (because of inspiration of 100% O2) were studied in the awake hamster
      window chamber model and compared with normoxia. Hyperoxia increased arterial
      blood Po2 to 477.9 +/- 19.9 from 60.0 +/- 1.2 mmHg (P < 0.05). Heart rate and
      blood pressure were unaltered, whereas cardiac index was reduced from 196 +/- 13
      to 144 +/- 31 ml.min-1.kg-1 (P < 0.05) in hyperoxia. Direct measurements in the
      microcirculation showed there was arteriolar vasoconstriction, reduction of
      microvascular flow (83% of control, P < 0.05), and functional capillary density
      (FCD, 74 +/- 16% of control), the latter change being significant (P < 0.05).
      Calculations of oxygen delivery and oxygen consumption based on the measured
      changes in microvascular blood flow velocity and diameter and estimates of oxygen
      saturation corrected for the Bohr effect due to the lowered pH and increased Pco2
      showed that oxygen transport in the microvascular network did not change between
      normal and hyperoxic condition. The congruence of systemic and microvascular
      hemodynamics events found with hyperoxia suggests that the microvascular findings
      are common to most tissues in the organism, and that hyperoxia, due to
      vasoconstriction and the decrease of FCD, causes a maldistribution of perfusion
      in the microcirculation.

PMID- 12805030
TI  - Myocardial oxygenation and high-energy phosphate levels during KATP channel
      blockade.
AB  - Inhibition of ATP-sensitive K+ (KATP) channel activity has previously been
      demonstrated to result in coronary vasoconstriction with decreased myocardial
      blood flow and loss of phosphocreatine (PCr). This study was performed to
      determine whether the high-energy phosphate abnormality during KATP channel
      blockade can be ascribed to oxygen insufficiency. Myocardial blood flow and
      oxygen extraction were measured in open-chest dogs during KATP channel blockade
      with intracoronary glibenclamide, whereas high-energy phosphates were examined
      with 31P magnetic resonance spectroscopy (MRS), and myocardial deoxymyoglobin (Mb
      delta) was determined with 1H MRS. Glibenclamide resulted in a 20 +/- 8% decrease
      of myocardial blood flow that was associated with a loss of phosphocreatine (PCr)
      and accumulation of inorganic phosphate. Mb-delta was undetectable during basal
      conditions but increased to 58 +/- 5% of total myoglobin during glibenclamide
      administration. This degree of myoglobin desaturation during glibenclamide was
      far greater than we previously observed during a similar reduction of blood flow
      produced by a coronary stenosis (22% of myoglobin deoxygenated during stenosis).
      The findings suggest that reduction of coronary blood flow with an arterial
      stenosis was associated with a decrease of myocardial energy demands and that
      this response to hypoperfusion was inhibited by KATP channel blockade.

PMID- 12805032
TI  - Insurgent multiculturalism: rethinking how and why we teach culture in medical
      education.
AB  - The author proposes a theoretical orientation for cultural competency that
      reorganizes common curricular responses to the study of culture in medical
      education. What has come to be known in medical education as cultural competency
      is theoretically truncated and may actually work against what educators hope to
      achieve. Using Giroux's concept of insurgent multiculturalism, she suggests that
      the critical study of culture might be a bridge to certain aspects of
      professional development. Insurgent multiculturalism moves inquiry away from a
      focus on nondominant groups to a study of how unequal distributions of power
      allow some groups but not others to acquire and keep resources, including the
      rituals, policies, attitudes, and protocols of medical institutions. This
      approach includes not only the doctor-patient relationship but also the social
      causes of inequalities and dominance. Linked to professional development efforts,
      insurgent multiculturalism can provide students with more opportunities to look
      at their biases, challenge their assumptions, know people beyond labels, confront
      the effects of power and privilege, and develop a far greater capacity for
      compassion and respect.

PMID- 12805033
TI  - Confronting "culture" in medicine's "culture of no culture".
AB  - The author presents reflections from medical anthropology on the institutional
      culture of medicine and medical education, which sees itself as a "culture of no
      culture" and which systematically tends to foster static and essentialist
      conceptions of "culture" as applied to patients. Even though requirements
      designed to address cultural competence are increasingly incorporated into
      medical school curricula, medical students as a group may be forgiven for failing
      to take these very seriously as long as they perceive that they are quite
      distinct from the real competence that they need to acquire. To change this
      situation will require challenging the tendency to assume that "real" and
      "cultural" must be mutually exclusive terms. Physicians' medical knowledge is no
      less cultural for being real, just as patients' lived experiences and
      perspectives are no less real for being cultural. Whether this lesson can be
      effectively conveyed within existing curricular frameworks remains an open
      question. Cultural competence curricula will, perhaps, achieve their greatest
      success if and when they put themselves out of business-if and when, that is,
      medical competence itself is transformed to such a degree that it is no longer
      possible to imagine it as not also being "cultural."

PMID- 12805034
TI  - Cross-cultural medical education: conceptual approaches and frameworks for
      evaluation.
AB  - Given that understanding the sociocultural dimensions underlying a patient's
      health values, beliefs, and behaviors is critical to a successful clinical
      encounter, cross-cultural curricula have been incorporated into undergraduate
      medical education. The goal of these curricula is to prepare students to care for
      patients from diverse social and cultural backgrounds, and to recognize and
      appropriately address racial, cultural, and gender biases in health care
      delivery. Despite progress in the field of cross-cultural medical education,
      several challenges exist. Foremost among these is the need to develop strategies
      to evaluate the impact of these curricular interventions. This article provides
      conceptual approaches for cross-cultural medical education, and describes a
      framework for student evaluation that focuses on strategies to assess attitudes,
      knowledge, and skills, and the impact of curricular interventions on health
      outcomes.

PMID- 12805035
TI  - Components of culture in health for medical students' education.
AB  - Medical educators across the United States are addressing the topics of culture,
      race, language, behavior, and social status through the development of cross
      cultural coursework. Dramatic demographic changes and nationwide attention to
      eliminating racial and ethnic health disparities make educating medical students
      about the importance of the effects of culture on health a 21st-century
      imperative. Despite the urgent need for including this topic material, few
      medical schools have achieved longitudinal integration of issues of culture into
      four-year curricula. The author makes the practical contribution of describing
      key themes and components of culture in health care for incorporation into
      undergraduate medical education. These include teaching the rationale for
      learning about culture in health care, "culture basics" (such as definitions,
      concepts, the basis of "culture" in the social sciences, relationship of culture
      to health and health care, and health systems as cultural systems), data on and
      concepts of health status (including demographics, epidemiology, health
      disparities, and the historical context), tools and skills for productive cross
      cultural clinical encounters (such as interviewing skills and the use of
      interpreters); characteristics and origins of attitudes and behaviors of
      providers; community participation (including the use of expert teachers,
      community-school partnerships, and the community as a learning environment); and
      the nature of institutional culture and policies.

PMID- 12805036
TI  - A strategy to reduce cross-cultural miscommunication and increase the likelihood
      of improving health outcomes.
AB  - Encounters between physicians and patients from different cultural backgrounds
      are becoming commonplace. Physicians strive to improve health outcomes and
      increase quality of life for every patient, yet these discordant encounters
      appear to be a significant factor, beyond socioeconomic barriers, in creating the
      unequal and avoidable excess burden of disease borne by members of ethnic
      minority populations in the United States. Most clinicians lack the information
      to understand how culture influences the clinical encounter and the skills to
      effectively bridge potential differences. New strategies are required to expand
      medical training to adequately address culturally discordant encounters among the
      physicians, their patients, and the families, for all three may have different
      concepts regarding the nature of the disease, expectations about treatment, and
      modes of appropriate communication beyond language. The authors provide an
      anthropological perspective of the fundamental relationship between culture and
      health, and outline systemic changes needed within the social and legal
      structures of the health care system to reduce the risk of cross-cultural
      miscommunication and increase the likelihood of improving health outcomes for all
      populations within the multicultural U.S. society. The authors define the
      strengths inherent within every culture, provide a guideline for the clinician to
      evaluate disease and illness within its cultural context, and outline the
      clinical skills required to negotiate among potential differences to reach
      mutually desired goals for care. Last, they indicate the structural changes
      required in the health care setting to enable and support such practice.

PMID- 12805037
TI  - Applying theory to the design of cultural competency training for medical
      students: a case study.
AB  - Although literature suggests that providing culturally sensitive care promotes
      positive health outcomes for patients, undergraduate medical education currently
      does not provide adequate cultural competency training. At most schools, cultural
      competency, as a formal, integrated, and longitudinal thread within the overall
      curriculum, is still in its infancy. In this article, the authors summarize the
      current practice of cultural competency training within medical education and
      describe the design, implementation, and evaluation of a theoretically based,
      year-long cultural competency training course for second-year students at Wake
      Forest University School of Medicine. Evaluation of the results indicate that the
      course was successful in improving knowledge, attitudes, and skills related to
      cultural competence as well as bringing about positive changes in the medical
      school's approach to cultural competency training. Also discussed are the
      implications of the outcomes for the development of culturally competent
      physicians and how using appropriate theory can help achieve desired outcomes.

PMID- 12805038
TI  - Combating effects of racism through a cultural immersion medical education
      program.
AB  - The purpose of this paper is to provide a perspective from New Zealand on the
      role of medical education in addressing racism in medicine. There is increasing
      recognition of racism in health care and its adverse effects on the health status
      of minority populations in many Western countries. New Zealand nursing curricula
      have introduced the concept of cultural safety as a means of conveying the idea
      that cultural factors critically influence the relationship between carer and
      patient. Cultural safety aims to minimize any assault on the patient's cultural
      identity. However, despite the work of various researchers and educators, there
      is little to suggest that undergraduate medical curricula pay much attention yet
      to the impact of racism on medical education and medical practice. The authors
      describe a cultural immersion program for third-year medical students in New
      Zealand and discuss some of the strengths and weaknesses of such an approach. The
      program is believed to have great potential as a method of consciousness raising
      among medical students to counter the insidious effects of non-conscious
      inherited racism. Apart from the educational benefits, the program has fostered a
      strong working relationship between an indigenous health care organization and
      the medical school. In general, it is hoped that such programs will help medical
      educators to engage more actively with the issue of racism and be prepared to
      experiment with novel approaches to teaching and learning. More specifically, the
      principles of cultural immersion, informed by the concept of cultural safety,
      could be adapted to indigenous and minority groups in urban settings to provide
      medical students with the foundations for a lifelong commitment to practicing
      medicine in a culturally safe manner.

PMID- 12805039
TI  - Training medical students to communicate with a linguistic minority group.
AB  - Effective communication is central to a successful physician-patient
      relationship. Communication is usually enhanced when the linguistic and cultural
      attributes of patients are incorporated in health care delivery. With this
      purpose in mind, the Faculty of Medicine at the University of Ottawa has
      developed a French-language stream to train future physicians for the francophone
      minority population of Ontario. As part of this project, a communication skills
      laboratory was created for francophone students in 1996, since all three tertiary
      care teaching hospitals operated in English only. The laboratory consists of a
      controlled environment where francophone students conduct interviews in French
      while being observed by clinicians trained in observation and feedback
      techniques. It makes use of simulated patients trained to play specific roles and
      to give feedback to students. Laboratory sessions take place throughout the first
      and second years and expose students to 15 scenarios covering different themes in
      each year. Each scenario includes a communication problem. Facilities are in
      place for filming the encounters for review by students. The project has had
      favorable outcomes. Both students and clinician-supervisors find that the
      laboratory offers an excellent learning environment and describe the cases as
      realistic and instructive. Clerkship preceptors are pleased with the students'
      communication skills. Because of the success of the laboratory, faculty
      authorities plan to translate the scenarios and offer similar sessions to
      students in the English-language stream. The teaching methods used in the
      communication skills laboratory may be of interest to other medical schools that
      serve linguistic minority populations.

PMID- 12805041
TI  - Teaching social and cultural awareness to medical students: "it's all very nice
      to talk about it in theory, but ultimately it makes no difference".
AB  - PURPOSE: To investigate the effect of exposure to a new course addressing social
      and cultural issues in medicine on third-year medical students' awareness and
      understanding of how these issues affect their lives as students, the lives of
      patients, the work of physicians, and patient-physician interaction. The course,
      Physicians, Patients & Society (PPS) was introduced at the time the school was
      moving to a PBL curriculum. METHOD: In the late 1990s, a questionnaire was
      administered to third-year medical students at one Canadian medical school, prior
      to the curriculum change (Time 1). In-depth interviews were held with 25 of these
      students. A few years later, the same methods were repeated (Time 2) with a third
      year class that had experienced the PPS course. RESULTS: The response rate for
      Time 1 was 59% (n = 72), for Time 2, 51% (n = 61). Students in Time 2 did not
      demonstrate increased awareness of social and cultural issues. Most failed to
      recognize, or even denied, the effects of race, class, gender, culture, and
      sexual orientation. Those who acknowledged the effect of social differences
      tended to deny social inequality, or at best recognized disadvantages experienced
      by Others, but not the accompanying privileges enjoyed by their own social group.
      CONCLUSIONS: In general, students concluded that learning about social and
      cultural issues made little or no difference when they did their clinical
      rotations. For a medical school to produce physicians who are sensitive to and
      competent working with diverse communities requires a balance between attention
      to "difference," attention to self, and attention to power relations.

PMID- 12805042
TI  - Cross-cultural education in U.S. medical schools: development of an assessment
      tool.
AB  - PURPOSE: Medical education is responding to an increasingly diverse population
      and to regulatory and quality-of-care requirements by developing cross-cultural
      curricula in health care. This undertaking has proved problematic because there
      is no consensus on what elements of cross-cultural medicine should be taught.
      Further, less is known about what is being taught. This study hypothesized that a
      tool could be developed to assess common themes, concepts, learning objectives,
      and methods in cross-cultural education. METHOD: In 2001, 31 U.S. medical schools
      were invited to provide the researchers all written and/or Web-based materials
      related to implementing cross-cultural competency in their curricula. A tool was
      developed to measure teaching methods, skill sets, and eight content areas in
      cross-cultural education. RESULTS: A total of 19 medical schools supplied their
      curricular materials. There was considerable variation in approaches to teaching
      and in the content of cross-cultural education across the schools. Most
      emphasized teaching general themes, such as the doctor-patient relationship,
      socioeconomic status, and racism. Most also focused on specific cultural
      information about the ethnic communities they served. Few schools extensively
      addressed health care access and language issues. CONCLUSIONS: This assessment
      tool is an important step toward developing a standard nomenclature for measuring
      the success of cross-cultural education curricula. On the national level, the
      tool can be used to compare program components and encourage the exchange of
      effective teaching tools by promoting a common language, which will be essential
      for developing and implementing curricula, for comparing programs, and evaluating
      their effects on quality of care.

PMID- 12805043
TI  - Serving as a physician role model for a diverse population of medical learners.
AB  - PURPOSE: Medical learners look to role models to better understand the values,
      attitudes, behaviors, and ethics of the medical profession. This study examined
      issues related to physicians serving as role models for diverse medical learners.
      METHOD: Between September and November 2000, in-depth semi-structured 30-minute
      interviews were conducted with 29 highly regarded role models, as judged by
      medical house officers at two large teaching hospitals in Baltimore, Maryland.
      Interview transcripts were independently coded and compared for agreement.
      Content analysis identified several major categories of themes that were examined
      and conceptually organized. RESULTS: The informants identified issues that relate
      to role modeling for diverse medical learners. Subcategories under the domain of
      similarity facilitates role modeling included learners prefer role models similar
      to them, role modeling is easier when the learner resembles the teacher, and
      minority physicians may be better role models for minority learners. Under the
      domain role modeling when physician-teachers and learners are different were the
      subcategories extra effort may be necessary, success promotes and inspires
      confidence, and role modeling across diversity is an achievable objective that
      should be pursued. The final domain, approaches to differences between physician
      teachers and learners, encompassed embrace diversity, act as a consultant and
      refer when necessary, and minimize and disregard all differences. CONCLUSIONS:
      The results of this study should draw attention to these issues and may serve as
      a stimulus for teaching physicians to consider a broader range of options for
      successful interactions with medical learners who are different from them.

PMID- 12805044
TI  - Are residents more comfortable than faculty members when addressing sociocultural
      diversity in medicine?
AB  - PURPOSE: Sociocultural medicine is a growing curricular area in medical
      education. Because faculty members and residents will teach these curricula and
      model these skills in patient care, it is important to assess their attitudes
      toward diversity. This study examined faculty members' and residents' attitudes
      toward sociocultural issues in medicine. METHOD: In November 2000, 198 physicians
      from the Department of Pediatrics at the University of Michigan Medical School
      completed a questionnaire on demographics and sociocultural attitudes in medicine
      while they attended a department-wide retreat on cultural competency. A factor
      analysis of the sociocultural attitudes measure yielded five dimensions
      accounting for 70% of the variance. These factors included sexual orientation,
      diversity in professional functions, discussing race/ethnicity in teaching
      forums, clinical skills, and alternative medicine. RESULTS: Significant
      differences were found between faculty members and residents for sexual
      orientation issues (t = 2.76, p <.01) and alternative medicine (t = 2.84, p
      <.01), with residents endorsing greater comfort in these areas of patient care.
      When controlling for demographic/background variables, group differences
      disappeared. Past exposure to multiculturalism emerged as a significant predictor
      for both sociocultural attitude dimensions. CONCLUSIONS: Findings suggested while
      residents felt more comfortable than faculty members did with sexual orientation
      and alternative medicine issues in medicine, attitudes may have been related more
      to previous diversity education than to seniority of the physician. Integrating
      diversity education within departments and across the medical education continuum
      likely benefits all physicians. In the area of sociocultural medicine, both
      faculty members and residents can offer perspectives valuable to medical
      students, colleagues, and the larger medical community.

PMID- 12805045
TI  - Beyond cultural competence.

PMID- 12805046
TI  - Why dying doesn't seem to matter: the influence of culture on physicians in Bali,
      Indonesia.

PMID- 12805047
TI  - Dying.

PMID- 12805049
TI  - The cost of operating institutional review boards (IRBs).
AB  - PURPOSE: Recent reports have claimed that institutional review boards (IRBs) are
      underfunded, yet little is known about the costs of operating IRBs. This study
      estimated the costs for operating high-volume and low-volume IRBs. METHOD: IRB
      costs were calculated from published summary data. Costs were standardized to
      reflect 2001 dollars. RESULTS: Total estimated costs for operating high-volume
      and low-volume IRBs were $770,674 and $76,626, respectively. The average cost per
      action, a measure of economic efficiency, was lower for high-volume IRBs ($277
      per action) than it was for low-volume IRBs ($799 per action). CONCLUSIONS:
      Although high-volume IRBs are more expensive than are low-volume IRBs in absolute
      terms, they are more economically efficient. Policy debates should consider the
      potential savings from large IRBs, perhaps by encouraging small IRBs to merge,
      although this may result in less local review, control, and oversight.

PMID- 12805050
TI  - Implementing a mission-based reporting system at an academic health center: a
      method for mission enhancement.
AB  - PURPOSE: To describe the utility of school-wide use of mission-based reporting
      (MBR) for medical school deans and department chairs. METHOD: All faculty members
      in the University of California, Davis, School of Medicine reported their
      clinical, creative, teaching, and service activities for 2000-2001 to the MBR
      system. The authors report on school-wide and department MBR profiles, and
      profiles by rank and academic series. They validate MBR by comparing individual
      results with actual merit actions reviewed independently by the school's academic
      personnel committee. RESULTS: A total of 419 faculty members (85%) completed
      their MBR reports. The average faculty member spent considerably more than 50
      hours per week fulfilling the missions of the school, and full professors and
      faculty members in academic series supported by state funds were the most
      productive in investigative and creative work. The teaching load was shared
      equally by all the academic ranks, although the clinician-scholars taught more
      than did faculty members in the other series. There was an inverse relationship
      between clinical load and academic rank, with the majority of the clinical work
      performed by junior faculty members. MBR results compared favorably with the
      merit review process, although MBR is not expected to replace the traditional
      peer review system. CONCLUSION: The creation of these graphic profiles and
      summaries is a valuable feature of MBR that would not have been possible without
      such quantitative data. The profiles allow monitoring to ensure that workload
      conforms to established objectives for individuals, departments, academic ranks
      and series. Finally, the authors discuss future directions for their MBR system.

PMID- 12805052
TI  - Junior faculty's perspectives on mentoring.
AB  - The prevalence and characteristics of mentorship among junior faculty in
      clinician-scientist and clinician-educator tracks were evaluated. Comprehensive
      improvement strategies are needed.

PMID- 12805053
TI  - Results of the National Resident Matching Program for 2003.

PMID- 12805054
TI  - Persistent Mycobacterium avium infection following nonmyeloablative allogeneic
      peripheral blood stem cell transplantation for interferon-gamma receptor-1
      deficiency.
AB  - Interferon-gamma receptor-1 (IFNgammaR1) deficiency is a rare inherited
      immunodeficiency. We performed a nonmyeloablative allogeneic stem cell
      transplantation on a boy with complete IFNgammaR1 deficiency and refractory
      disseminated Myco- bacterium avium infection. Despite the patient's profound
      immune defect, early donor stem cell engraftment was low. Full donor engraftment
      was accomplished only following multiple donor lymphocyte infusions. Detection of
      IFNgammaR1 expression on peripheral blood monocytes and neutrophils corresponded
      with establishment of stable, complete donor hematopoietic chimerism. However,
      expression of, and signaling through IFNgammaR1 disappeared shortly thereafter.
      Disseminated Mycobacterium avium infection persisted and the patient died.
      Coculture of Myco- bacterium avium with normal myeloid cells resulted in an
      IFNgamma signaling defect similar to that observed in vivo. Active disseminated
      Mycobacterium avium infection may significantly compromise normal immune
      reconstitution following allogeneic stem cell transplantation. Patients with
      IFNgammaR1 deficiency should receive transplants before developing refractory
      mycobacterial infections.

PMID- 12805055
TI  - Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes
      in iron metabolism induced by doxorubicin.
AB  - The clinical use of doxorubicin (DOX), an anthracycline chemotherapeutic agent,
      is limited by cardiotoxicity. The possible involvement of iron in DOX-induced
      cardiotoxicity became evident from studies in which iron chelators were shown to
      be cardioprotective. Iron overload is found in hereditary hemochromatosis, a
      genetic disorder prevalent in individuals of European descent. We hypothesized
      that Hfe deficiency may increase susceptibility to DOX-induced toxicity. Acute
      cardiotoxicity and iron changes were studied after treatment with DOX in Hfe
      knock-out (Hfe-/-) mice and wild-type mice. DOX-induced iron metabolism changes
      were intensified in Hfe-/- mice, which accumulated significantly more iron in the
      heart, liver, and pancreas, but less in the spleen compared with wild-type mice.
      In addition, Hfe-deficient mice exhibited significantly greater sensitivity to
      DOX-induced elevations in serum creatine kinase and aspartate aminotransferase.
      Increased mortality after chronic DOX treatment was observed in Hfe-/- mice and
      Hfe+/-mice compared with wild-type mice. DOX-treated Hfe-/- mice had a higher
      degree of mitochondrial damage and iron deposits in the heart than did wild-type
      mice. These data demonstrate that Hfe deficiency in mice increases susceptibility
      to DOX-induced cardiotoxicity and suggest that genetic mutations related to
      defects in iron metabolism may contribute to its cardiotoxicity in humans.

PMID- 12805056
TI  - Labile plasma iron in iron overload: redox activity and susceptibility to
      chelation.
AB  - Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for
      catalyzing the formation of reactive radicals in the circulation of iron
      overloaded subjects, resulting in accumulation of oxidation products. We assessed
      the redox active component of NTBI in the plasma of healthy and beta-thalassemic
      patients. The labile plasma iron (LPI) was determined with the fluorogenic
      dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted
      by ascorbate but blocked by iron chelators. The assay was LPI specific since it
      was generated by physiologic concentrations of ascorbate, involved no sample
      manipulation, and was blocked by iron chelators that bind iron selectively. LPI,
      essentially absent from sera of healthy individuals, was present in those of beta
      thalassemia patients at levels (1-16 microM) that correlated significantly with
      those of NTBI measured as mobilizer-dependent chelatable iron or desferrioxamine
      chelatable iron. Oral treatment of patients with deferiprone (L1) raised plasma
      NTBI due to iron mobilization but did not lead to LPI appearance, indicating that
      L1-chelated iron in plasma was not redox active. Moreover, oral L1 treatment
      eliminated LPI in patients. The approach enabled the assessment of LPI
      susceptibility to in vivo or in vitro chelation and the potential of LPI to cause
      tissue damage, as found in iron overload conditions.

PMID- 12805057
TI  - The protein kinase C inhibitor RO318220 potentiates thrombin-stimulated platelet
      supported prothrombinase activity.
AB  - Prothrombinase activity was tested on thrombin- and SFLLRN-activated platelets
      treated with RO318220, a potent inhibitor of protein kinase C. RO318220
      completely inhibited platelet dense and alpha-granule secretion at a
      concentration of 20 microM but had no effect on prothrombinase activity in the
      presence of excess factor Va (20 nM). This indicates that protein kinase C
      activity and agonist-initiated secretion are not necessary for the development of
      a procoagulant surface. Treatment with 75 to 150 microM RO318220 potentiated
      platelet-supported thrombin generation up to 280% of control platelets with no
      change in Kd appFXa. Treated with increasing concentrations of RO318220, an
      increasing proportion of thrombin-stimulated platelets bound annexin V with
      decreasing binding sites per platelet. A lower mean forward scatter (FSC-H) of
      platelets treated with RO318220 suggested platelet vesiculation as a result of
      RO318220 treatment; however, 100 microM calpeptin pretreatment eliminated the
      decrease in FSC-H without affecting either the increase in platelets positive for
      annexin V binding, the decrease in binding sites per platelet, or the 3-fold
      increase in prothrombinase activity. Thus, RO318220 appears to increase
      prothrombinase activity by increasing platelet responsiveness to thrombin rather
      than by inducing platelet vesiculation. This suggests that RO318220 inhibits a
      signaling molecule within a negative regulatory pathway that governs platelet
      procoagulant surface changes.

PMID- 12805058
TI  - Sickle blood contains tissue factor-positive microparticles derived from
      endothelial cells and monocytes.
AB  - Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived
      only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes
      are activated and abnormally express tissue factor (TF). Thus, sickle blood might
      contain TF-positive MPs derived from these cells. With the use of flow cytometry
      to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P
      =.0001) and steady state (P =.02) in subjects with sickle cell disease versus
      control subjects. These MPs were derived from erythrocytes, platelets, monocytes,
      and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (P
      =.0001) and steady state (P =.02) versus control subjects, as were monocyte
      derived MPs (P =.0004 and P =.009, respectively). Endothelial and platelet
      derived MPs were elevated in sickle crisis versus control subjects. Total TF
      positive MPs were elevated in sickle crisis versus steady state (P =.004) and
      control subjects (P <.0001) and were derived from both monocytes and endothelial
      cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a
      TF antibody partially inhibited this procoagulant activity. Markers of
      coagulation were elevated in patients with sickle cell disease versus control
      subjects and correlated with total MPs and TF-positive MPs (P <.01 for both).
      These data support the concept that SCD is an inflammatory state with monocyte
      and endothelial activation and abnormal TF activity.

PMID- 12805059
TI  - The recurrent IgH translocations are highly associated with nonhyperdiploid
      variant multiple myeloma.
AB  - Aneuploid is ubiquitous in multiple myeloma (MM), and 4 cytogenetic subcategories
      are recognized: hypodiploid (associated with a shorter survival), pseudodiploid,
      hyperdiploid, and near-tetraploid MM. The hypodiploid, pseudodiploid, and near
      tetraploid karyotypes can be referred to as the nonhyperdiploid MM.
      Immunoglobulin heavy-chain (IgH) translocations are seen in 60% of patients. We
      studied the relation between aneuploidy and IgH translocations in MM. Eighty
      patients with MM and abnormal metaphases were studied by means of interphase
      fluorescent in situ hybridization (FISH) to detect IgH translocations. We also
      studied a second cohort of 199 patients (Eastern Cooperative Oncology Group
      [ECOG]) for IgH translocations, chromosome 13 monosomy/deletions (Delta13), and
      ploidy by DNA content. Mayo Clinic patients with abnormal karyotypes and FISH
      detected IgH translocation were more likely to be nonhyperdiploid (89% versus
      39%, P <.0001). Remarkably, 88% of tested patients with hypodiploidy (16 of 18)
      and 90% of tested patients with tetraploidy (9 of 10) had an IgH translocation.
      ECOG patients with IgH translocations were more likely to have nonhyperdiploid MM
      by DNA content (68% versus 21%, P <.001). This association was seen predominantly
      in patients with recurrent chromosome partners to the IgH translocation (11q13,
      4p16, and 16q23). The classification of MM into hyperdiploidy and
      nonhyperdiploidy is dictated largely by the recurrent (primary) IgH
      translocations in the latter.

PMID- 12805060
TI  - AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence,
      partner chromosomes, FAB subtype, age distribution, and prognostic impact in an
      unselected series of 1897 cytogenetically analyzed AML cases.
AB  - Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL
      gene comprise one category of recurring genetic abnormalities in the WHO
      classification. In an unselected series of 1897 AML cases, 54 patients with an
      11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The
      incidence of AML with MLL rearrangement was significantly higher in therapy
      related AML (t-AML) than in de novo AML (9.4% vs 2.6%, P <.0001). The frequency
      of MLL rearrangements was significantly higher in patients younger than 60 years
      (5.3% vs 0.8%, P <.0001). While the incidence of MLL rearrangements in AML M4,
      M5a, and M5b was 4.7%, 33.3%, and 15.9%, respectively, it was found in only 0.9%
      of all other French-American-British (FAB) subtypes (P <.0001). Compared with AML
      with intermediate karyotype, AML with 11q23/MLL rearrangement had a worse
      outcome, which was rather comparable with AML with unfavorable karyotype.
      Compared with t-AML, the median overall survival (OS) of de novo AML with MLL
      rearrangement was significantly better (2.5 vs 10 months, P =.0143). No
      significant differences in median OS were observed between cases with t(9;11)
      compared with all other MLL rearrangements (10.0 vs 8.9 months, P =.36). In
      conclusion, the category AML with 11q23/MLL abnormalities accounts for 2.8% of
      unselected AML, is closely associated with monocytic differentiation, and has a
      dismal prognosis. (

PMID- 12805061
TI  - Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial
      antigen-presenting cells expressing a single HLA allele.
AB  - Cytomegalovirus (CMV) is a major threat in patients undergoing allogeneic bone
      marrow transplantation. The adoptive transfer of CMV-specific cytotoxic T
      lymphocytes (CTLs) expanded from the blood of CMV-seropositive donors has been
      shown to effectively control CMV infection. However, the requirement for safe and
      effective antigen-presenting cells (APCs) for each patient precludes broad
      applicability of this successful form of therapy. Here we analyze the ability of
      artificial APCs (AAPCs) to activate and expand CMV-specific CTLs from peripheral
      blood of seropositive HLA A2.1+ donors. We demonstrate that AAPCs expressing the
      CMV P495 peptide or the full-length pp65 protein stimulate P495-specific CTLs at
      least as effectively as autologous, peptide-pulsed, peripheral blood mononuclear
      cells or EBV-transformed B cells. Starting from 100 mL of blood, the AAPCs
      reliably yield clinically relevant CTL numbers after a single stimulation. CTLs
      activated on AAPCs effectively kill CMV-infected fibroblasts and have a Tc1
      memory effector phenotype identical to that of CTLs generated with autologous
      APCs. AAPCs thus offer a rapid, controlled, convenient, and highly reproducible
      system for expanding CMV-specific CTLs. Furthermore, the CTL expansion obtained
      with AAPCs encoding full-length pp65 indicates that AAPCs may be used to present
      known as well as unknown CTL epitopes in the context of the AAPC's HLA.

PMID- 12805062
TI  - A gene-deleted adenoviral vector results in phenotypic correction of canine
      hemophilia B without liver toxicity or thrombocytopenia.
AB  - Many approaches for treating hemophilia via gene transfer have been attempted in
      large animal models but all have potential drawbacks. Recombinant adenoviral
      vectors offer high-efficiency transfer of an episomal vector but have been
      plagued by the cytotoxicity/immunogenicity of early-generation vectors that
      contain viral genes. In our current study, we have used a nonintegrating helper
      dependent (HD) adenoviral vector for liver-directed gene transfer to achieve
      hemostatic correction in a dog with hemophilia B. We measured plasma canine
      factor IX (cFIX) concentrations at a therapeutic range for up to 2.5 months and
      normalization of the whole blood clotting time (WBCT) for about a month. This was
      followed by a decrease and stabilized partial correction for 4.5 months. Hepatic
      gene transfer of a slightly lower dose of the HD vector resulted in WBCTs that
      were close to normal for 2 weeks, suggesting a dose threshold effect in dogs. In
      sharp contrast to other studies using first- or second-generation adenoviral
      vectors, we observed no vector-related elevation of liver enzymes, no fall in
      platelet counts, and normal liver histology. Taken together, this study
      demonstrates that injection of an adenoviral HD vector results in complete but
      transient phenotypic correction of FIX deficiency in canine models with no
      detectable toxicity.

PMID- 12805063
TI  - Recombinant BbetaArg14His fibrinogen implies participation of N-terminus of Bbeta
      chain in desA fibrin polymerization.
AB  - We synthesized BbetaArg14His fibrinogen with histidine substituted for arginine
      at the Bbeta thrombin-cleavage site. This substitution led to a 300-fold decrease
      in the rate of thrombin-catalyzed fibrinopeptide B (FpB, Bbeta 1-14) release,
      whereas the rate of FpA release was normal with either thrombin or the FpA
      specific enzyme, batroxobin. Both thrombin- and batroxobincatalyzed
      polymerization of BbetaArg14His fibrinogen were significantly impaired, with a
      longer lag time, slower rate of lateral aggregation, and decreased final
      turbidity. Moreover, desA monomer polymerization was similarly impaired,
      demonstrating that the histidine substitution itself, and not the lack of FpB
      cleavage, caused the abnormal polymerization of BbetaArg14His fibrin. Scanning
      electron microscopy showed BbetaArg14His fibrin fibers were thinner than normal
      (BbetaArg14His, approximately 70 nm; normal, approximately 100 nm; P <.0001), as
      expected from the decreased final turbidity. We conclude that the N-terminus of
      the Bbeta chain is involved in the lateral aggregation of normal desAprotofibrils
      and that the Arg-->His substitution disrupts these interactions in BbetaArg14His
      fibrinogen.

PMID- 12805064
TI  - IL-15 induces antigen-independent expansion and differentiation of human naive
      CD8+ T cells in vitro.
AB  - Recent studies in mice have shown that although interleukin 15 (IL-15) plays an
      important role in regulating homeostasis of memory CD8+ T cells, it has no
      apparent function in controlling homeostatic proliferation of naive T cells. We
      here assessed the influence of IL-15 on antigen-independent expansion and
      differentiation of human CD8+ T cells. Both naive and primed human T cells
      divided in response to IL-15. In this process, naive CD8+ T cells successively
      down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with
      these phenotypic changes, naive cells acquired the ability to produce interferon
      gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), expressed perforin
      and granzyme B, and acquired cytotoxic properties. Primed CD8+ T cells, from both
      noncytotoxic (CD45RA-CD27+) and cytotoxic (CD45RA+CD27-) subsets, responded to IL
      15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells.
      In summary, all human CD8+ T-cell subsets had the ability to respond to IL-15,
      which suggests a generic influence of this cytokine on CD8+ T-cell homeostasis in
      man.

PMID- 12805065
TI  - Phenotype and hematopoietic potential of side population cells throughout
      embryonic development.
AB  - Adult murine bone marrow hematopoietic stem cells (HSCs) can be purified by
      sorting Hoechst 33342-extruding side population (SP) cells. Herein we
      investigated whether SP cells reside within embryonic tissues and exhibit
      hematopoietic progenitor activity. We isolated yolk sac (YS) and embryonic
      tissues 7.5 to 11.5 days after coitus (dpc), resolved an SP in each, and
      demonstrated that these SP cells exhibit distinct phenotypic and functional
      characteristics throughout development. YS and embryonic SP isolated 8.0 dpc
      expressed vascular endothelial-cadherin (VE-cadherin) and vascular endothelial
      receptor 2 (Flk-1), markers not expressed by bone marrow SP but expressed by
      endothelial cells and progenitors. SP at this stage did not express CD45 or
      produce hematopoietic colonies in vitro. In contrast, SP isolated 9.5 to 11.5 dpc
      contained a significantly higher proportion of cells expressing cKit and CD45,
      markers highly expressed by bone marrow SP. Furthermore, YS SP isolated 9.5 to
      11.5 dpc demonstrated 40- to 90-fold enrichment for hematopoietic progenitor
      activity over unfractionated tissue. Our data indicate that YS and embryonic SP
      cells detected prior to the onset of circulation express the highest levels of
      endothelial markers and do not generate blood cells in vitro; however, as
      development progresses, they acquire hematopoietic potential and phenotypic
      characteristics similar to those of bone marrow SP.

PMID- 12805066
TI  - Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX
      2 expression in endothelial cells.
AB  - Reporter genes, including green fluorescent protein (GFP), have been used to
      monitor the expression of transgenes introduced into vascular cells by gene
      transfer vectors. Here, we demonstrate that GFP by itself can selectively induce
      expression of certain genes in endothelial cells. Elevation of the cytoplasmic
      concentration of GFP in endothelial cells, specifically, resulted in a robust
      upregulation of heat shock protein 70 (HSP70). GFP induced both mRNA and protein
      expression of HSP70 in a dose-dependent manner. GFP-mediated up-regulation of
      HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin
      E2 (PGE2) production. GFP-mediated up-regulation of HSP70 is independent of
      mitogen-activated protein kinase and phosphatidylinositol-3-kinase signaling
      cascades because inhibition of these pathways had no effect on HSP70 increases.
      Adenoviral delivery of GFP into murine vasculature significantly enhanced blood
      flow, suggesting that sufficient PGE2 is produced to induce vasodilation.
      Identification of the molecular partners that interact with GFP will increase our
      understanding of the vascular-specific factors that regulate stress angiogenesis
      and hemostasis.

PMID- 12805067
TI  - A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha
      production by monocytes.
AB  - MyD-1 (CD172) is a member of the family of signal regulatory phosphatase (SIRP)
      binding proteins, which is expressed on human CD14+ monocytes and dendritic
      cells. We now show a novel role for MyD-1 in the regulation of the innate immune
      system by pathogen products such as lipopolysaccharide (LPS), purified protein
      derivative (PPD), and Zymosan. Specifically, we demonstrate that ligation of MyD
      1 on peripheral blood mononuclear cells (PBMCs) inhibits tumor necrosis factor
      alpha (TNFalpha) secretion but has no effect on other cytokines induced in
      response to each of these products. In an attempt to understand the molecular
      mechanisms underlying this surprisingly selective effect we investigated signal
      transduction pathways coupled to MyD-1. Ligation of the SIRP was found to recruit
      the tyrosine phosphatase SHP-2 and promote sequential activation of
      phosphatidylinositol (PI) 3-kinase, phospholipase D, and sphingosine kinase.
      Inhibition of LPS-induced TNFalpha secretion by MyD-1 appears to be mediated by
      this pathway, as the PI 3-kinase inhibitor wortmannin restores normal LPS-driven
      TNFalpha secretion. MyD-1-coupling to this PI 3-kinase-dependent signaling
      pathway may therefore present a novel target for the development of therapeutic
      strategies for combating TNFalpha production and consequent inflammatory disease.

PMID- 12805068
TI  - Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency
      virus type-1 replication and affects cytoskeleton organization in human monocyte
      derived macrophages.
AB  - CC chemokine ligand 2 (CCL2) is constitutively expressed at high levels in human
      peripheral blood monocytes, and its expression is further up-modulated during
      their differentiation into macrophages as well as in the course of HIV infection.
      To investigate the role of endogenous CCL2 on HIV replication and macrophage
      function, CCL2's activity was neutralized by specific antibodies. Infection of
      monocyte-derived macrophages with laboratory-adapted HIV-1 or primary viral
      isolates in the continuous presence of anti-CCL2 antibody resulted in
      significantly lower p24 Gag antigen release with respect to control cultures.
      Interestingly, CCL2 neutralization did not affect the early steps of the HIV life
      cycle but resulted in the intracellular accumulation of p24 Gag antigen.
      Simultaneously, remarkable changes in cell morphology and size occurred in cell
      cultures maintained in the presence of anti-CCL2 antibody. These results suggest
      that CCL2 may represent an autocrine factor important for enhancing virion
      production likely by affecting the macrophage cytoskeleton.

PMID- 12805069
TI  - Differential expression and regulation of protease-activated receptors in human
      peripheral monocytes and monocyte-derived antigen-presenting cells.
AB  - Protease-activated receptors (PARs) are stimulated by proteolytic cleavage of
      their extracellular domain, unmasking a new N-terminus acting as tethered ligand.
      Whereas the role of PARs in platelets is well known, their presence and function
      in human monocytes and other antigen-presenting cells has not been characterized.
      Here it is demonstrated that human peripheral monocytes and monocyte-derived
      macrophages and dendritic cells differentially express PARs. Human monocytes
      express mainly PAR1 and less PAR3. Differentiation of monocytes into macrophages
      by either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) elicits enhanced expression of PAR1, PAR2, and
      PAR3. In contrast, dendritic cells differentiated from monocytes by GM-CSF and
      interleukin-4 (IL-4) strongly down-regulated PAR1, PAR2, and PAR3, both at the
      mRNA and the protein level. Down-regulation of the PAR expression was apparently
      due to IL-4, because treatment of macrophages with IL-4 caused down-regulation of
      PAR1, PAR2, and PAR3. PAR4 mRNA expression remained undetectable in any of the
      cell types investigated. Stimulation of PAR1, PAR2, and PAR3 with thrombin,
      trypsin, or established receptor-activating peptides (PAR-APs) triggered
      cytosolic Ca2+ responses, indicating functionally active PARs. Further,
      stimulation of monocytes or macrophages with thrombin or PAR1-AP, but not with
      PAR2-or PAR4-AP, triggers expression of monocyte chemoattractant protein-1 (MCP
      1) both at the mRNA and the protein level. These data demonstrate that
      differentiation of human monocytes is associated with differential expression of
      functionally active PARs that mediate distinct regulatory functions in
      inflammation and atherogenesis.

PMID- 12805070
TI  - Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of
      hypertension and ischemic heart disease: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to investigate whether the M235T
      polymorphism in the angiotensinogen gene was associated with angiotensinogen
      levels, systolic and diastolic blood pressure, hypertension, and risk of ischemic
      cardiovascular disease in different ethnic populations. METHODS AND RESULTS: One
      hundred twenty-seven studies published between January 1992 and March 2002
      examining the association of angiotensinogen gene polymorphisms with the above
      mentioned end points were selected. Pooled effect sizes and Mantel-Haenszel odds
      ratios were calculated using Review Manager. In white subjects, genotype was
      associated with a stepwise increase in plasma angiotensinogen levels of 5% (95%
      CI, 2% to 8%; P=0.0004) in MT heterozygotes and 11% (7% to 15%; P<0.00001) in TT
      homozygotes compared with MM individuals. Correspondingly, genotype was
      associated with a stepwise increase in aggregated odds ratio for hypertension of
      1.08 (95% CI, 1.01 to 1.15) in MT individuals and 1.19 (1.10 to 1.30) in TT
      individuals in white subjects and of 1.29 (95% CI, 0.96 to 1.74) and 1.60 (1.19
      to 2.15) in Asian subjects. M235T genotype did not predict systolic or diastolic
      blood pressure or risk of ischemic heart disease or myocardial infarction in
      either ethnic group. CONCLUSIONS: Angiotensinogen M235T genotype was associated
      with a stepwise increase in angiotensinogen levels in white subjects and a
      corresponding increase in risk of hypertension in both white and Asian subjects.

PMID- 12805071
TI  - Intravascular modalities for detection of vulnerable plaque: current status.
AB  - Progress in the diagnosis, treatment, and prevention of atherosclerotic coronary
      artery disease is dependent on a greater understanding of the mechanisms of
      coronary plaque progression. Autopsy studies have characterized a subgroup of
      high-risk, or vulnerable, plaques that result in acute coronary syndromes or
      sudden cardiac death. These angiographically modest plaques share certain
      pathologic characteristics: a thin, fibrous cap, lipid-rich core, and macrophage
      activity. Diagnostic techniques for vulnerable-plaque detection, including
      serologic markers and noninvasive and invasive techniques, are needed. Recent
      advances in intravascular imaging have significantly improved the ability to
      detect high-risk, or vulnerable, plaque in vivo by using various features of
      plaque vulnerability as methods of identification. The characteristic anatomy of
      a thin, fibrous cap overlying a lipid pool has promoted high-resolution imaging,
      such as intravascular ultrasound, optical coherence tomography, and intracoronary
      magnetic resonance. The lipid-rich core is identifiable by angioscopically
      detected color changes on the plaque surface or by its unique absorption of
      energy, or "Raman shift," of its cholesterol core, driving coronary spectroscopy.
      Finally, temperature heterogeneity arising at foci of plaque inflammation has
      prompted the development of intracoronary thermography. In this review, we will
      discuss these techniques, their relative advantages and limitations, and their
      potential clinical application.

PMID- 12805072
TI  - Oxidized phospholipid-induced endothelial cell/monocyte interaction is mediated
      by a cAMP-dependent R-Ras/PI3-kinase pathway.
AB  - OBJECTIVE: Previous studies have demonstrated the importance of endothelial
      apical expression of connecting segment-1 (CS-1) fibronectin in mediating the
      entry of monocytes into atherosclerotic lesions and other sites of chronic
      inflammation. We previously demonstrated that oxidized PAPC (OxPAPC) increases
      monocyte-specific binding to arterial endothelium by causing deposition of CS-1
      fibronectin on apical alpha5beta1 integrin. The present studies identify
      important signal transduction components regulating this pathway. METHODS AND
      RESULTS: Using endothelial cells in culture, we demonstrate that activation of R
      Ras is responsible for CS-1-mediated monocyte binding. Although few natural
      activators of R-Ras have been demonstrated, OxPAPC activated endothelial R-Ras by
      2.5-fold but decreased levels of activated H-Ras. The importance of R-Ras/H-Ras
      balance in regulating monocyte binding was shown by overexpression studies.
      Constitutively active R-Ras enhanced monocyte adhesion, whereas coexpression with
      constitutively active H-Ras was inhibitory. Elevated cAMP, mediated by OxPAPC and
      specific components POVPC and PEIPC, was responsible for R-Ras activation, and
      dibutyryl cAMP and pertussis toxin were also effective activators of R-Ras. Using
      inhibitor and dominant-negative constructs, we demonstrated that
      phosphatidylinositol 3-kinase (PI3K) was a key downstream effector of R-Ras in
      this pathway. CONCLUSIONS: OxPAPC, POVPC, and PEIPC induce a cAMP/R-Ras/PI3K
      signaling pathway that contributes to monocyte/endothelial cell adhesion and
      potentially atherosclerosis.

PMID- 12805073
TI  - Constitutively active glycogen synthase kinase-3beta gene transfer sustains
      apoptosis, inhibits proliferation of vascular smooth muscle cells, and reduces
      neointima formation after balloon injury in rats.
AB  - OBJECTIVE: Glycogen synthase kinase (GSK)-3beta is a crucial factor in many
      cellular signaling pathways and may play an important role in smooth muscle
      proliferation and apoptosis after angioplasty. METHODS AND RESULTS: To
      investigate the effect of GSK-3beta modulation on neointima formation, smooth
      muscle proliferation, and apoptosis after balloon injury in vivo, we delivered
      adenoviral vectors expressing the constitutively active form of GSK-3beta (GSK
      S9A: 9th serine switched to alanine) or a control gene into rat carotid arterial
      segments after balloon injury with a 2F Fogarty catheter. Viral infusion mixtures
      (5x108 pfu) were incubated in the arterial lumen for 20 minutes, and the effects
      of gene delivery were evaluated 3 days and 2 weeks after gene delivery with
      morphometry and immunohistochemical staining for proliferating and apoptotic
      cells. There were no significant differences in intimal, medial, and lumen areas
      at 3 days after the procedure. However, 2 weeks after gene delivery, the active
      GSK-3beta gene transfer resulted in a significantly lower intima to media ratio
      (0.29+/-0.06 versus 0.86+/-0.09, P<0.01) and a greater lumen area (0.41+/-0.02
      versus 0.31+/-0.01 mm2, P<0.01) compared with the control gene transfected group.
      This was attributable to a significant reduction in intimal area (0.05+/-0.01
      versus 0.15+/-0.02 mm2, P<0.01), whereas the medial area was similar (0.17+/-0.01
      versus 0.18+/-0.01 mm2, P=0.21). Proliferation index was significantly reduced
      both at 3 days and 2 weeks in the active GSK-3beta gene transferred group (2.97+/
      0.29% versus 5.71+/-0.50%, P<0.01). In addition, apoptotic index, which was not
      significantly different between the 2 groups at 3 days, was significantly higher
      in the active GSK-3beta gene transferred group at 2 weeks (3.14+/-0.68% versus
      22.7+/-1.63%, n=10, P<0.01, for control versus active GSK-3beta gene transfer).
      CONCLUSIONS: In vivo delivery of the active GSK-3beta gene inhibits smooth muscle
      proliferation, sustains apoptosis, and reduces neointima formation after balloon
      injury in rats and may be a future therapeutic target to limit neointima
      hyperplasia after angioplasty.

PMID- 12805074
TI  - Paraoxonase activity, but not haplotype utilizing the linkage disequilibrium
      structure, predicts vascular disease.
AB  - OBJECTIVE: The effects of paraoxonase (PON1) activity and of genetic variation in
      the PON1 promoter and coding region on carotid artery disease (CAAD) were
      investigated. METHODS AND RESULTS: We identified functional promoter
      polymorphisms and examined their effects in a cohort with and without CAAD. We
      used the full sequences in 23 white subjects to determine the linkage
      disequilibrium (LD) structure of the PON1 region and to direct the grouping of
      haplotypes for disease association testing. There are several discrete regions of
      the PON1 gene with strong local LD, but the useful levels of LD do not extend
      across the entire gene. Indeed, PON1-162/-108/55/192 haplotype did not predict
      additional variation in PON1 activities compared with the 4 genotypes separately.
      PON1 hydrolysis activity predicted CAAD status, but this was not attributable to
      the promoter or coding region polymorphisms or haplotype or to the effects of
      smoking or statin use on PON1 activity. CONCLUSIONS: PON1 does not have LD across
      the gene, and use of haplotypes in association studies should consider the LD
      structure. PON1 activity predicts CAAD, yet 4 functional polymorphisms do not.
      Additional investigations of genetic and environmental factors that influence
      PON1 activity as a risk factor for vascular disease are warranted.

PMID- 12805075
TI  - Novel proangiogenic effect of factor XIII associated with suppression of
      thrombospondin 1 expression.
AB  - OBJECTIVE: Factor XIII (FXIII), a plasma transglutaminase that stabilizes fibrin
      clots at the final stages of blood coagulation by crosslinking fibrin monomers,
      is essential for embryo implantation and participates in tissue remodeling and
      wound healing, processes that involve angiogenesis. The aim of our study was to
      analyze the effect of FXIII on angiogenesis using in vitro and in vivo models and
      to examine the role of FXIII in the basic steps of angiogenesis, ie, migration,
      proliferation, and apoptosis/cell survival. METHODS AND RESULTS: In the Matrigel
      tube formation model, only FXIIIa caused a dose-dependent enhancement of array
      formation. This proangiogenic effect was not associated with alterations in
      vascular endothelial growth factor (VEGF) protein levels nor VEGF or VEGFR2 mRNA
      levels. FXIIIa, but not nonactivated or transglutaminase-inactivated FXIII,
      significantly enhanced endothelial cell migration and proliferation and inhibited
      apoptosis. After treatment of HUVECs with FXIIIa, almost complete disappearance
      of mRNA of thrombospondin 1 (TSP-1) and a marked reduction in the secretion of
      TSP-1 protein were observed. A reduction in TSP-1 protein synthesis, although to
      a lesser extent, was observed on treatment of microvascular endothelial cells
      with FXIIIa. In a rabbit cornea model, injection of FXIIIa caused
      neovascularization associated with almost complete disappearance of TSP-1 in the
      cornea. CONCLUSIONS: These results show that FXIIIa exhibits a novel
      proangiogenic activity that is associated with downregulation of TSP-1 and also
      involves stimulation of endothelial cell proliferation and migration and
      inhibition of apoptosis. These findings might shed light on the mechanism by
      which FXIII mediates tissue repair and remodeling.

PMID- 12805076
TI  - Interaction of oxidative stress and inflammatory response in coronary plaque
      instability: important role of C-reactive protein.
AB  - OBJECTIVE: C-reactive protein (CRP), a predictor of cardiovascular events,
      localizes in atherosclerotic arteries and exerts proinflammatory effects on
      vascular cells. Reactive oxygen species (ROS) have been implicated in
      atherogenesis and plaque instability. METHODS AND RESULTS: Expressional pattern
      of CRP in directional coronary atherectomy specimens from 39 patients was
      examined. Characteristics of histological plaque instability and higher levels of
      serum CRP and fibrinogen were associated with the CRP immunoreactivity. In situ
      hybridization revealed the presence of CRP mRNA in coronary vasculature.
      Furthermore, the expression of CRP mRNA and protein was detected in cultured
      human coronary artery smooth muscle cells (CASMCs) by reverse transcriptase
      polymerase chain reaction and Western blotting. In addition, CRP was frequently
      colocalized with p22phox, an essential component of NADH/NADPH oxidase, which is
      an important source of ROS in vasculature. Moreover, the incubation of cultured
      CASMCs with CRP resulted in the enhanced p22phox protein expression and in the
      generation of intracellular ROS. CONCLUSIONS: The expression of CRP in coronary
      arteries was associated with histological and clinical features of vulnerable
      plaque, and it had a prooxidative effect on cultured CASMCs, suggesting that it
      might play a crucial role in plaque instability and in the pathogenesis of acute
      coronary syndrome via its prooxidative effect.

PMID- 12805077
TI  - A cis-acting region regulates oxidized lipid-mediated induction of the human heme
      oxygenase-1 gene in endothelial cells.
AB  - OBJECTIVE: Several proatherogenic agents including oxidized LDL and its major
      component, 13-hydroperoxyoctadecadienoic acid (13-HPODE), upregulate heme
      oxygenase-1 (HO-1). Our previous studies have demonstrated that 13-HPODE-mediated
      HO-1 induction occurs via transcriptional mechanisms. The purpose of this study
      was to evaluate the molecular regulation and identify the signaling pathways
      involved in 13-HPODE-mediated HO-1 induction in human aortic endothelial cells.
      METHODS AND RESULTS: The half-life of HO-1 mRNA after stimulation with 13-HPODE
      was approximately 1.8 hours. Antioxidants such as N-acetylcysteine, iron
      chelation with deferoxamine mesylate, and protein kinase C inhibition with Go6976
      blocked HO-1 induction. Using promoter constructs up to 9.1 kb, no significant
      reporter activity was observed in response to 13-HPODE. A 13-HPODE-inducible
      DNase I hypersensitive site was identified that maps to a region approximately 10
      to 11 kb from the transcription start site of the human HO-1 gene. Based on the
      DNase I analysis, a -11.6-kb human HO-1 promoter construct was generated and
      elicited a 2.5-fold increase in reporter activity, indicating that 13-HPODE
      mediated human HO-1 induction requires, at least in part, sequences that reside
      between 9.1 and 11.6 kb of the human HO-1 promoter. CONCLUSIONS: Elucidation of
      the molecular mechanisms which control HO-1 gene expression will allow us to
      develop therapeutic strategies to enhance the cytoprotective potential of HO-1 in
      atherosclerosis.

PMID- 12805078
TI  - Adrenomedullin reduces VEGF-induced endothelial adhesion molecules and
      adhesiveness through a phosphatidylinositol 3'-kinase pathway.
AB  - OBJECTIVE: In the initial phase of inflammation, vascular endothelial growth
      factor (VEGF) can act as a proinflammatory cytokine by inducing adhesion
      molecules that bind leukocytes to endothelial cells. Adrenomedullin (AM) is known
      to act as either a proinflammatory or an anti-inflammatory agent. In this study,
      we examined the effects of AM on adhesion molecule expression and leukocyte
      adhesiveness in VEGF-stimulated human umbilical vein endothelial cells. METHODS
      AND RESULTS: When stimulated with VEGF, the mRNAs of intercellular adhesion
      molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin
      were dose-dependently upregulated. AM inhibited the VEGF-induced protein and mRNA
      expression of ICAM-1, VCAM-1, and E-selectin. Phosphatidylinositol 3'-kinase
      inhibitor and a dominant-negative form of Akt significantly inhibited the
      suppressive effect of AM on VEGF-induced adhesion molecule expression. Thus, AM
      inhibits VEGF-stimulated ICAM-1 and VCAM-1 expression through a
      phosphatidylinositol 3'-kinase/Akt pathway. AM reduced VEGF-induced endothelial
      adhesiveness for leukocytes. CONCLUSIONS: These results suggest that AM might
      have an anti-inflammatory role in controlling VEGF-induced adhesion molecule gene
      expression and adhesiveness toward leukocytes in endothelial cells.

PMID- 12805079
TI  - Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans
      and is actively metabolized by dimethylarginine dimethylaminohydrolase.
AB  - OBJECTIVE: Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor,
      asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure,
      hypertension, and chronic heart failure. In patients with renal failure, plasma
      ADMA levels are an independent correlate of left ventricular ejection fraction.
      However, the cardiovascular effects of a systemic increase in ADMA in humans are
      not known. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled
      study in 12 healthy male volunteers, we compared the effects of intravenous low
      dose ADMA and placebo on heart rate, blood pressure, cardiac output, and systemic
      vascular resistance at rest and during exercise. We also tested the hypothesis
      that ADMA is metabolized in humans in vivo by dimethylarginine
      dimethylaminohydrolase (DDAH) enzymes. Low-dose ADMA reduced heart rate by 9.2+/
      1.4% from 58.9+/-2.0 bpm (P<0.001) and cardiac output by 14.8+/-1.2% from 4.4+/
      0.3 L/min (P<0.001). ADMA also increased mean blood pressure by 6.0+/-1.2% from
      88.6+/-3.4 mm Hg (P<0.005) and SVR by 23.7+/-2.1% from 1639.0+/-91.6 dyne. s. cm
      5 (P<0.001). Handgrip exercise increased cardiac output in control subjects by
      96.8+/-23.3%, but in subjects given ADMA, cardiac output increased by only 35.3+/
      10.6% (P<0.05). DDAHs metabolize ADMA to citrulline and dimethylamine. Urinary
      dimethylamine to creatinine ratios significantly increased from 1.26+/-0.32 to
      2.73+/-0.59 after ADMA injection (P<0.01). We estimate that humans generate
      approximately 300 micromol of ADMA per day, of which approximately 250 micromol
      is metabolized by DDAHs. CONCLUSIONS: This study defines the cardiovascular
      effects of a systemic increase in ADMA in humans. These are similar to changes
      seen in diseases associated with ADMA accumulation. Finally, our data also
      indicate that ADMA is metabolized by DDAHs extensively in humans in vivo.

PMID- 12805080
TI  - A morphological and quantitative characterization of early floral development in
      apple (Malus x domestica Borkh.).
AB  - Apple is an important crop and a focus of research worldwide. However, some
      aspects of floral commitment and morphogenesis remain unclear. A detailed
      characterization of bourse shoot apex development was undertaken to provide a
      framework for future genetic, molecular and physiological studies. Eight
      morphologically distinct stages of shoot apex development, prior to winter
      dormancy, were defined. Based on measurements of meristem diameter, two stages of
      vegetative development were recognized. Vegetative meristems were flat, and
      either narrow (stage 0) or broad (stage 1). Pronounced doming of the apex marked
      stage 2. During stage 3, the domed meristem initiated four to six lateral floral
      meristems and subtending bracts before converting to a terminal floral meristem
      (stage 4). The terminal floral meristem proceeded directly with bractlet and
      sepal initiation, while lateral floral meristems initiated bractlets (stage 5).
      Sepal initiation began on the basal lateral flower (stage 6) and continued in an
      acropetal direction until all floral meristems had completed sepal initiation
      (stage 7). In this study, only stage 0 and stage 7 apices were observed in
      dormant buds, indicating that stages 1-6 are transient. The results suggest that
      broadening of the apex (stage 1) is the first morphological sign of commitment to
      flowering.

PMID- 12805081
TI  - Incorporating a chronology response into the prediction of leaf appearance rate
      in winter wheat.
AB  - The prediction of leaf appearance rate (LAR) is an important part of many crop
      simulation models. Most wheat simulations models assume that LAR is affected by
      temperature and photoperiod. This assumption ignores the fact that seed reserves
      contribute to a greater LAR of the first two leaves and that the LAR of
      subsequent leaves decreases as a result of an increase in the distance that each
      leaf primordium must extend before it appears. The objective of this study was to
      develop a generalized LAR chronology response function [f(C)] for wheat that
      takes into account seed reserves and the increasing distance from the meristem to
      the whorl for later appearing leaves. This chronology response function was then
      incorporated into an existing LAR model [Wang and Engel (WE) model; Wang and
      Engel, 1998, Agricultural Systems 58: 1-24]. This function varied from 0 to 1,
      being equal to 1 for the first two leaves due to seed reserves, and decreasing
      (taking the form of a power law) for subsequent leaves. Data from a growth
      chamber (two cultivars) and several field experiments (four cultivars, two years
      and eight sowing dates) at Lincoln, Nebraska, USA, were used as independent data
      to test three LAR models (Miglietta model, Miglietta, 1991, Climate Research 1:
      145-150; WE model; and modified WE model). Predictions of the main stem Haun
      stage, both in the growth chamber and in the field, were greatly improved by
      incorporating f(C) into the Wang and Engel model. The root mean square error for
      the field data was 1.1, 0.7, and 0.3 leaves for the Miglietta model, the Wang and
      Engel model, and the modified Wang and Engel model, respectively.

PMID- 12805082
TI  - Relationship between maximum leaf photosynthesis, nitrogen content and specific
      leaf area in balearic endemic and non-endemic mediterranean species.
AB  - Gas exchange parameters, leaf nitrogen content and specific leaf area (SLA) were
      measured in situ on 73 C3 and five C4 plant species in Mallorca, west
      Mediterranean, to test whether species endemic to the Balearic Islands differed
      from widespread, non-endemic Mediterranean species and crops in their leaf traits
      and trait inter-relationships. Endemic species differed significantly from
      widespread species and crops in several parameters; in particular, photosynthetic
      capacity, on an area basis (A), was 20 % less in endemics than in non-endemics.
      Similar differences between endemics and non-endemics were found in parameters
      such as SLA and leaf nitrogen content per area (Na). Nevertheless, most of the
      observed differences were found only within the herbaceous deciduous species.
      These could be due to the fact that most of the non-endemic species within this
      group have adapted to ruderal areas, while none of the endemics occupies this
      kind of habitat. All the species-including the crops-showed a positive, highly
      significant correlation between photosynthetic capacity on a mass basis (Am),
      leaf nitrogen content on a mass basis (Nm) and SLA. However, endemic species had
      a lower Am for any given SLA and Nm. Hypotheses are presented to explain these
      differences, and their possible role in reducing the distribution of many endemic
      Balearic species is discussed.

PMID- 12805083
TI  - Floral longevity and nectar secretion of Platanthera chlorantha (Custer) Rchb.
      (Orchidaceae).
AB  - Flowering and nectar secretion were studied in Platanthera chlorantha in two
      years. Nectar was secreted and accumulated in this orchid's spur, originating
      from part of the labellum. The nectary spur was, on average, 32 mm long. It
      produced 6.86 micro l nectar in 1999 and 7.84 micro l in 2000. The number of
      flowers per inflorescence and the volume of nectar secreted per flower were not
      correlated. Nectar secretion and flower longevity differed depending on
      pollination and flower position in the inflorescence. Among pairs of pollinated
      and unpollinated flowers there was no difference in the volume of nectar
      produced; however, the life span of pollinated flowers was shorter than that of
      unpollinated ones. Within an inflorescence, the lowest-positioned flowers had the
      largest nectar production and the longest life compared with flowers positioned
      higher up.

PMID- 12805084
TI  - Periods of organogenesis in mono- and bicyclic annual shoots of Juglans regia L.
      (Juglandaceae).
AB  - The organogenetic cycle of shoots on main branches of 4-year-old Juglans regia
      trees was studied. Mono- and bicyclic floriferous and vegetative annual shoots
      were analysed. Five parent annual shoot types were sampled between October 1992
      and August 1993. Organogenesis of summer growth units was monitored between 16
      Jun. and 3 Aug. 1993. Variations over time in the number of nodes, cataphylls and
      embryonic green leaves of terminal buds were studied. The number of nodes of
      parent shoot buds was compared with the number of nodes of shoots derived from
      parent shoot buds. The spring growth units of mono- and bicyclic shoots consist
      exclusively of preformed leaves which were differentiated, respectively, during
      the spring flush of growth (mid-April until mid-May) or the summer flush of
      growth (mid-June until early August) in the previous growing season. Thus, winter
      buds may consist of flower and leaf primordia differentiated in two different
      periods during annual shoot extension. The summer growth units of bicyclic shoots
      consist of preformed leaves that were differentiated in spring buds during the
      spring flush of growth in the current growing season. Bud morphology is compared
      between spring and summer shoots.

PMID- 12805085
TI  - Monocyte chemoattractant protein-4 core promoter genetic variants: influence on
      YY-1 affinity and plasma levels.
AB  - Monocyte chemoattractant protein-4 (MCP-4) is a CC chemokine implicated in the
      recruitment of eosinophils, monocytes, and T-lymphocytes in diseases of mucosal
      inflammation, including asthma. We tested the hypothesis that there is a genetic
      basis for differences in MCP-4 expression among individuals by evaluating the
      effects of core promoter variants on MCP-4 expression. We identified two single
      nucleotide T-to-C polymorphisms in the MCP-4 core promoter that occur 896 and 887
      base pairs preceding the transcription initiation site. The -887 variant alters a
      consensus binding motif for the transcription factor YY-1. Electrophoretic
      mobility shift assay demonstrated that YY-1 containing nuclear extracts from
      tumor necrosis factor-alpha-stimulated peripheral blood mononuclear cells had
      greater avidity for the wild-type (YY-1 motif intact) sequence than for the
      variant sequence. Increasing doses of a YY-1 expression vector induced
      significantly greater reporter activity from MCP-4 core promoter expression
      constructs of the wild-type compared with the variant sequence in transient
      transfection experiments. The external validity of these observations was
      demonstrated by measuring plasma levels of MCP-4 from individuals with the
      alternative forms of the gene. Individuals bearing haplotypic variants of the MCP
      4 core promoter that avidly bind the transcription factor YY-1 had higher plasma
      levels of MCP-4 than did individuals with variants with lower binding avidity
      (490, 360, and 360 pg/ml; P < 0.01). Our findings suggest that the MCP-4 core
      promoter YY-1 binding motif is functional, modulates the transcriptional
      regulation of the MCP-4 gene, and that part of the variance in the systemic
      expression of MCP-4 is determined by core promoter genetic variants.

PMID- 12805086
TI  - Pulmonary and activation-regulated chemokine stimulates collagen production in
      lung fibroblasts.
AB  - Levels of pulmonary and activation-regulated chemokine (PARC) mRNA and protein
      are increased in the lungs of patients with pulmonary fibrosis. The purpose of
      this study was to establish whether PARC could be directly involved in
      development of pulmonary fibrosis by stimulating collagen production in lung
      fibroblasts. Exposure to PARC increased production of collagen mRNA and protein
      by 3- to 4-fold in normal adult lung and dermal fibroblast cells. Collagen mRNA
      transiently increased after 3-6 h of activation with PARC, with an increase in
      collagen protein detected after 24 h of activation. At the same time, PARC had
      less pronounced effect on fibroblast proliferation, not exceeding 50% increase
      over control nonstimulated cells. PARC intracellular signaling led to activation
      of ERK1/2, but not p38, in fibroblasts; pharmacologic inhibition of ERK, but not
      p38, also blocked PARC's effect on collagen production. Inhibition experiments
      with pertussis toxin suggested that PARC receptor is G protein-coupled. Thus,
      PARC is a member of the CC chemokine family that acts directly as a profibrotic
      factor.

PMID- 12805087
TI  - Peroxisome proliferator-activated receptor-gamma is deficient in alveolar
      macrophages from patients with alveolar proteinosis.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand
      activated, nuclear transcription factor that regulates genes involved in lipid
      and glucose metabolism, inflammation, and other pathways. The hematopoietic
      growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is
      essential for lung homeostasis and is thought to regulate surfactant clearance,
      but mechanisms involved are unknown. GM-CSF is reported to stimulate PPAR-gamma,
      but the activation status of PPAR-gamma in human alveolar macrophages has not
      been defined. In pulmonary alveolar proteinosis (PAP), a rare interstitial lung
      disease, surfactant accumulates in alveolar airspaces, resident macrophages
      become engorged with lipoproteinaceous material, and GM-CSF deficiency is
      strongly implicated in pathogenesis. Here we show that PPAR-gamma mRNA and
      protein are highly expressed in alveolar macrophages of healthy control subjects
      but severely deficient in PAP in a cell-specific manner. Further, we show that
      the PPAR-gamma-regulated lipid scavenger receptor, CD36, is also deficient in
      PAP. PPAR-gamma and CD36 deficiency are not intrinsic to PAP alveolar
      macrophages, but can be upregulated by GM-CSF therapy. Moreover, GM-CSF treatment
      of patients with PAP fully restores PPAR-gamma to healthy control levels. Based
      upon these novel findings, we hypothesize that GM-CSF regulates lung homeostasis
      via PPAR-gamma-dependent pathways.

PMID- 12805088
TI  - NO mediates effects of estrogen on central regulation of blood pressure in
      restrained, ovariectomized rats.
AB  - We tested the hypotheses that estrogen replacement in ovariectomized (OVX) rats
      attenuates cardiovascular responses to psychological stress and that nitric oxide
      (NO) in the brain mediates these effects. Female rats were OVX; one group
      received 17beta-estradiol (OVX-E) for 11-12 days and the other received vehicle
      (OVX-V). Seven days after OVX, OVX-E and OVX-V rats were chronically instrumented
      for arterial pressure measurements and intracerebroventricular injections. Later
      (4-5 days), OVX-E and OVX-V rats received intracerebroventricular injections of
      NG-nitro-l-arginine (88 microg/kg), an inhibitor of constitutive NO production,
      or vehicle. Mean arterial pressure (MAP) and heart rate responses were then
      measured in conscious rats exposed to two cycles of 1-h restraint/1-h rest. We
      show that MAP responses in restrained OVX-E rats were attenuated both during
      restraint and during rest. Although inhibition of NO production in the brain had
      no effect on MAP responses to restraint in OVX-V rats, it augmented responses in
      restrained OVX-E rats, especially during periods of rest, so that MAPs in
      restrained OVX-E and OVX-V rats were indistinguishable. Finally, NO levels in
      hypothalami and brain stems were elevated in restrained OVX-E, but not OVX-V,
      rats compared with their respective unrestrained controls. These results show
      that estrogen replacement in OVX rats reduces arterial pressure responses to
      psychological stress and that these effects are mediated, at least in part, by
      NO.

PMID- 12805089
TI  - IGF-I gene transfer effects on inflammatory elements present after thermal
      trauma.
AB  - Major thermal injury results in severe prolonged responses with three components:
      a hypermetabolic response, inflammatory responses, and endogenous wound-healing
      processes. We showed that use of liposome-mediated gene transfer of the insulin
      like growth factor I (IGF-I) reduces burn-induced inflammatory responses and
      enhances wound healing. In the present study, we found transient increased levels
      of IGF-I protein in rats exposed to thermal trauma via liposomal gene transfer in
      an effort to define the transcriptional events that occur after IGF-I delivery at
      the site of injury. The beneficial effects of IGF-I gene transfer act partly via
      amelioration of burn-induced inflammatory responses that mediate cell death
      through caspase-3 activity and Bax expression. IGF-I gene transfer induces
      selective stimulation of activation protein-1 DNA-binding activity and activation
      of antiapoptotic, but not inflammatory, NF-kappaB transcription factors. Data
      were consistent with our hypothesis that the beneficial effects of IGF-I gene
      transfer on burned rats act in part via activation protein-1 and NF-kappaB
      transcriptional regulation and the concordance between the results obtained with
      antiapoptotic, as opposed to the proapoptotic, sequences as well as the
      corresponding changes in measures of cell death via Bax and caspase-3 mechanisms.

PMID- 12805090
TI  - Dynamic interactions between arterial pressure and sympathetic nerve activity:
      role of arterial baroreceptors.
AB  - The role of arterial baroreceptors in controlling arterial pressure (AP)
      variability through changes in sympathetic nerve activity was examined in
      conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured
      continuously during 1-h periods in freely behaving rats that had been subjected
      to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before
      study (n = 10 in each group). Fast Fourier transform analysis revealed that
      chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related
      oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral
      power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing
      the so-called Mayer waves, and induced an eightfold increase in MAP power without
      altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of
      rats, coherence between RSNA and MAP was maximal in the MF band and was usually
      weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP
      showed the characteristics of a second-order low-pass filter containing a fixed
      time delay ( approximately 0.5 s). These results indicate that arterial
      baroreceptors are not involved in production of respiratory-related oscillations
      of RSNA but play a major role in the genesis of synchronous oscillations of MAP
      and RSNA at the frequency of Mayer waves. The weak coupling between slow
      fluctuations of RSNA and MAP in sham-operated and SAD rats points to the
      interference of noise sources unrelated to RSNA affecting MAP and of noise
      sources unrelated to MAP affecting RSNA.

PMID- 12805091
TI  - Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice.
AB  - Aberrant gene-environment interactions are implicated in the pathogenesis of
      congenital renal dysgenesis (CRD), a leading cause of renal failure in infants
      and children. We have recently developed an animal model of CRD that is caused by
      gestational salt stress (5% NaCl diet; HS) of bradykinin B2R null mice [B2R(-/
      )CRD; El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S.
      Physiol Genomics 3: 121-131, 2000.]. Developing B2R(-/-)CRD mice exhibit tubular
      and glomerular cysts, stromal expansion, and loss of corticomedullary
      differentiation. In addition, B2R(-/-)CRD mice exhibit transient hypertension
      from 2 to 4 mo of age. The present study was designed to determine the long-term
      consequences of CRD on renal morphology and salt sensitivity of blood pressure in
      B2R(-/-)CRD mice. One-year- and 18-mo-old B2R(-/-)CRD mice exhibited stunted
      renal growth, glomerular cystic abnormalities, and collecting duct ectasia.
      Moreover, tumors of mesenchymal cell origin emerged in the dysplastic kidneys of
      90% of 1-yr-old and 100% of 18-mo-old B2R(-/-)CRD mice but not in age-matched
      B2R(-/-) or wild-type mice. When challenged with an HS diet, 18-mo-old B2R(-/
      )CRD exhibited a significant rise in systolic and diastolic blood pressures and
      more pronounced natriuresis and diuresis compared with salt-loaded 18-mo-old wild
      type mice. Kidney aquaporin-2 expression was decreased by 50%, whereas renin, ANG
      type 1 receptor, and Na+-K+-ATPase levels were not different in B2R(-/-)CRD mice
      compared with controls. In conclusion, this study demonstrates that B2R(-/-)CRD
      mice exhibit permanent phenotypic and functional abnormalities in renal growth
      and differentiation. This novel model of human disease links gene-environment
      interactions with renal development and blood pressure homeostasis.

PMID- 12805092
TI  - Dynamic synchronization analysis of venous pressure-driven cardiac output in
      rainbow trout.
AB  - Measurement of venous function in vivo is inherently difficult. In this study, we
      used the Hilbert transform to examine the dynamic relationships between venous
      pressure and cardiac output (CO) in rainbow trout whose blood volume was
      continuously increased and decreased by ramp infusion and withdrawal (I/W). The
      dorsal aorta and ductus Cuvier were cannulated percutaneously and connected to
      pressure transducers; a flow probe was placed around the ventral aorta. Whole
      blood from a donor was then I/W via the dorsal aortic cannula at a rate of 10% of
      the estimated blood volume per minute, and the duration of I/W was varied from
      40, 60, 80, 90, 120, 230, 240, 260, 300, and 340 s. Compliance [change in (delta)
      blood vol/deltavenous pressure] was 2.8 +/- 0.2 ml x mmHg-1x g-1 (N = 25
      measurements; 6 fish with closed pericardium) and 2.8 +/- 0.3 ml. mmHg-1x kg-1 (N
      = 19 measurements, 4 fish with open pericardium). Compliance was positively
      correlated with the duration of I/W, indicative of cardiovascular reflex
      responses at longer I/W durations. In trout with closed pericardium, CO followed
      venous pressure oscillations with an average time lag of 4.2 +/- 1.0 s (N = 9);
      heart rate (HR) was inversely correlated with CO. These studies show that CO is
      entrained by modulation of venous pressure, not by HR. Thus, although trout have
      a rigid pericardium, venous pressure (vis-a-tergo), not cardiac suction (vis-a
      fronte), appears to be the primary determinant of CO. Estimation of venous
      compliance by ramp-modulation of venous pressure is faster and less traumatic
      than classical capacitance measurements and appears applicable to a variety of
      vertebrate species, as does the Hilbert transform, which permits analysis of
      signals with disparate frequencies.

PMID- 12805093
TI  - Exercise training differentially modifies age-associated alteration in expression
      of Na+-K+-ATPase subunit isoforms in rat skeletal muscles.
AB  - The present study tests the hypothesis that endurance exercise training (ETr)
      reverses age-associated alterations in expression of Na+-K+-ATPase subunit
      isoforms in rat skeletal muscles. Expression of the isoforms was examined in 16
      mo-old sedentary middle-aged, 29-mo-old sedentary senescent, and 29-mo-old
      treadmill exercise-trained senescent Fischer 344 x Brown Norway rats. Levels of
      the alpha1-isoform increased with age in red gastrocnemius (GR), white
      gastrocnemius (GW), and extensor digitorum longus (EDL) muscles, and ETr further
      increased its levels. Levels of the alpha2-isoform were unchanged in GR, had a
      strong trend for a decrease in GW, and decreased significantly in EDL. ETr
      increased expression of the alpha2-isoform in all three muscle groups. There was
      no increase in expression of the beta1-isoform in GR, GW, or EDL with age,
      whereas ETr markedly increased its levels in the muscles. There was a marked
      decrease with age in expression of the beta2-isoform in the muscle groups that
      was not reversed by ETr. By contrast, beta3-isoform levels increased with age in
      GR and GW, and ETr was able to reverse this increase. Na+-K+-ATPase enzyme
      activity was unchanged with age in GR and GW but increased in EDL. ETr increased
      enzyme activity in GR and GW and did not change in EDL. Myosin heavy chain
      isoforms in the muscle groups did not change significantly with age; ETr caused a
      general shift toward more oxidative fibers. Thus ETr differentially modifies age
      associated alterations in expression of Na+-K+-ATPase subunit isoforms, and a
      mechanism(s) other than physical inactivity appears to play significant role in
      some of the age-associated changes.

PMID- 12805094
TI  - Subcellular distribution of ryanodine receptors in the cardiac muscle of carp
      (Cyprinus carpio).
AB  - We examined the subcellular localization of ryanodine receptors (RyR) in the
      cardiac muscle of carp using biochemical, immunohistochemical, and electron
      microscopic methods and compared it with those of rats and guinea pigs. To
      achieve this goal, an anti-RyR antibody was newly raised against a synthetic
      peptide corresponding to an amino acid sequence that was conserved among all
      sequenced RyRs. Western blot analysis using this antibody detected a single RyR
      band following the SDS-PAGE of sarcoplasmic reticulum (SR) membranes from carp
      atrium and ventricle as well as from mammalian hearts and skeletal muscles. The
      carp heart band had slightly greater mobility than those of mammalian hearts.
      Although immunohistochemical staining showed evident striations corresponding to
      the Z lines in longitudinal sections of mammalian hearts, clusters of punctate
      staining, in contrast, were distributed ubiquitously throughout carp atrium and
      ventricle. Electron microscopic images of the carp myocardium showed that the SR
      was observed largely as the subsarcolemmal cisternae and the reticular SR,
      suggesting that the RyR is localized in the junctional and corbular SR.

PMID- 12805095
TI  - Pure lateral medullary infarction: clinical-radiological correlation of 130
      acute, consecutive patients.
AB  - Although there have been attempts to make clinical-MRI correlation in patients
      with lateral medullary infarction (LMI), studies with a large number of patients
      are unavailable. In this study, clinical features, MRI findings and angiogram
      results of 130 acute, consecutive patients with pure LMI were studied and
      correlated. MRI-identified lesions were classified rostro-caudally as rostral,
      middle and caudal, and horizontally as typical, ventral, large, lateral and
      dorsal. The distribution of horizontal subtypes was significantly different (P
      <0.001) among three rostro-caudal lesions in that rostral lesions tend to be
      ventral types and caudal lesions are lateral types. Patients with rostrally
      located lesions had dysphagia, facial paresis (P < 0.01, each) and dysarthria (P
      < 0.05) significantly more often, and severe gait ataxia and headache (P < 0.05,
      each) less often than those with caudal lesions. The frequencies of dysphagia (P
      < 0.01), dysarthria (P < 0.01) and bilateral trigeminal sensory pattern (P <
      0.05) were significantly different among horizontal subtypes in that these
      symptoms were frequent in patients with "large type" as compared with those with
      lateral type lesions. Angiograms performed in 123 patients showed vertebral
      artery (VA) disease in 67% and posterior inferior cerebellar artery (PICA)
      disease in 10%. The presumed pathogenetic mechanisms included large vessel
      infarction in 50%, arterial dissection in 15%, small vessel infarction in 13% and
      cardiac embolism in 5%. Dissection occurred more often in patients with caudal
      (versus rostral) lesions (P < 0.01), whereas dorsal type infarcts (versus other
      types) were related more often to cardiogenic embolism and normal angiogram
      findings (P < 0.05, each). Patients with isolated PICA disease (versus those with
      VA disease) more often had cardiogenic embolism (P < 0.05) and less often had
      dissection (P < 0.01). It is concluded that rostro-caudal and horizontal
      classification of MRI helps us to understand the clinical and, partly, the
      aetiopathogenetic aspect of the heterogeneous LMI syndrome.

PMID- 12805096
TI  - Minimum birth prevalence of mitochondrial respiratory chain disorders in
      children.
AB  - Mitochondrial respiratory chain disorders comprise a group of perhaps several
      hundred different genetic diseases. Each individual disorder is rare, but
      collectively they account for substantial use of health care resources. However,
      few accurate data on prevalence are available due to problems such as variation
      in clinical presentation, age of onset, referral practices and limitations of
      diagnostic methodologies. With this retrospective study, we aimed to determine
      the minimum birth prevalence of respiratory chain disorders that have onset in
      childhood, that is the proportion of births that will have onset of symptoms
      caused by a respiratory chain defect by 16 years of age. Of the 1 706 694
      children born in the three south-eastern states of Australia (New South Wales,
      Victoria and South Australia) between January 1st 1987 and December 31st 1996,
      samples from 430 were referred for investigation of a respiratory chain disorder.
      Definite diagnosis of a respiratory chain disorder was made in 86 cases based on
      defined clinical, pathological, enzyme and molecular criteria. Age at
      presentation ranged from 0 to 129 months (median 4 months). The total data set
      predicts a minimum birth prevalence for respiratory chain disorders in children
      of 5.0/100 000 [95% confidence interval (CI) 4.0-6.2]. A significantly higher
      figure of 58.6/100 000 (95% CI 34.7-92.6) was noted for Australian families of
      Lebanese origin. Clinical awareness of respiratory chain disorders and
      investigation methods have improved since 1987, but not all affected children
      would have been recognized as such from the more recent years. The minimum birth
      prevalence of 6.2/100 000 (95% CI 4.5-8.4) for the 43 patients born between 1991
      and 1994 is thought to be a more accurate estimate for respiratory chain
      disorders presenting in childhood. Combining our data with a previous study on
      prevalence of adult-onset respiratory chain disorders predicts a minimum birth
      prevalence of 13.1/100 000 or 1/7634 for respiratory chain disorders with onset
      at any age.

PMID- 12805097
TI  - Parkinson's disease: piecing together a genetic jigsaw.
AB  - The role of genetics in the pathogenesis of Parkinson's disease has been subject
      to debate for decades. In recent years, the discovery of five genes and several
      more loci has provided important insight into its molecular aetiology. Some
      Parkinson's disease genes possibly cause Parkinson's disease by protein
      aggregation. The presence of Lewy bodies in carriers of mutations in one gene and
      their absence in carriers of another, however, still point towards a complex
      pathogenic network, with Parkinson's disease as a common clinical end point. The
      recent identification of the fourth and fifth Parkinson's disease genes suggests
      multiple pathways-an impaired oxidative stress defence for mutations in DJ-1, and
      a defect in another signalling pathway for mutations in NR4A2. Despite knowledge
      of genetics in familial Parkinson's disease, our knowledge of the common, late
      onset form of Parkinson's disease remains limited. In non-familial Parkinson's
      disease, genes and environment probably interact to give rise to the disease. We
      review advances in the genetics of Parkinson's disease, focusing on the monogenic
      forms and their clinical and population-genetic consequences.

PMID- 12805098
TI  - Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation
      with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia.
AB  - We identified an oligophrenin 1 (OPHN1) gene mutation in a family with five
      brothers affected by a recognizable pattern of clinical and neuroradiological
      hallmarks. The distinctive phenotype comprised moderate to severe mental
      retardation, myoclonic-astatic epilepsy, ataxia, strabismus and hypogenitalism.
      Neuroimaging displayed fronto-temporal atrophy with rostral enlargement of the
      lateral ventricles, lower vermian agenesis and asymmetric cerebellar hypoplasia.
      Mutation analysis of the OPHN1 gene on Xq12 disclosed a genomic deletion of exon
      19 causing a frameshift. Notably, OPHN1 mutations have been previously reported
      as a rare cause of non-syndromic X-linked mental retardation. Our findings,
      however, indicate that OPHN1 mutations result in a recognizable syndrome. In
      addition, identification of OPHN1 as a further gene associated with epileptic
      seizures will help to unravel aetiologic factors of epilepsy.

PMID- 12805099
TI  - Clinical and molecular findings in a patient with a novel mutation in the
      deafness-dystonia peptide (DDP1) gene.
AB  - The Mohr-Tranebjaerg syndrome (MTS) is a rare neurodegenerative disorder
      characterized by early-onset deafness, dystonia and further neurological
      abnormalities such as cortical blindness, spasticity, dementia and mental
      retardation. Causative mutations were identified within the deafness-dystonia
      peptide (DDP1/TIMM8a) gene on the X-chromosome. The DDP1 protein is located in
      the intermembrane space of human mitochondria. Here, it acts in a complex
      together with its partner protein Tim13 in a chaperone-like manner to facilitate
      the import of nuclear-encoded precursor proteins into the mitochondrial inner
      membrane. Thus, MTS is a novel type of mitochondrial disorder. To obtain more
      insight into the pathophysiology of this neurodegenerative disorder, we performed
      for the first time a comprehensive clinical and functional characterization of a
      patient suffering from MTS. This patient exhibited a typical combination of
      deafness, dystonia and visual loss. Sequence analysis of the patient's DDP1 gene
      revealed a G to C transversion at nucleotide position 38 of the first exon. The
      mutation affects the ATG start codon, thereby changing methionine to isoleucine
      (M1I), and leads to a complete absence of the DDP1 protein. In addition, the
      partner protein Tim13 was found to be significantly reduced, suggesting that
      Tim13 requires the presence of DDP1 for its stabilization. The assessment of
      mitochondrial functions showed the enzyme activities of the mitochondrial energy
      generating systems to be normal in the muscle biopsy. Structural abnormalities or
      aggregations of mitochondria were absent. Electron microscopy revealed only a
      mild neurogenic atrophy. Neurophysiological investigations showed cochlear
      dysfunction and disturbance of visual pathways. PET and MRI studies revealed a
      multifocal pattern of neurodegeneration with hypometabolic areas predominantly
      located over the right striatum and parietal cortex and marked atrophy of the
      occipital lobes. Although the visual loss is caused predominantly by
      neurodegeneration of the visual cortex, degeneration of the retina and the optic
      nerve contributes to the visual impairment. The pathological changes in basal
      ganglia and sensory cortex demonstrate the disintegration of subcortico-cortical
      circuits and correlate well with the clinical presentation of multifocal
      dystonia. The data presented here showed that, in contrast to most of the known
      mitochondrial disorders, MTS appears not to be associated with a functional
      defect of the energy generation system of the mitochondria. Whereas the specific
      mitochondrial dysfunction leading to neuronal loss in MTS remains to be
      clarified, the electrophysiological and neuroimaging findings allowed the
      multifocal manifestation of neurodegenerative lesions in MTS to be characterized
      specifically.

PMID- 12805100
TI  - Focal thinning of the cerebral cortex in multiple sclerosis.
AB  - Brain atrophy as determined by quantitative MRI can be used to characterize
      disease progression in multiple sclerosis. Many studies have addressed white
      matter (WM) alterations leading to atrophy, while changes of the cerebral cortex
      have been studied to a lesser extent. In vivo, the cerebral cortex has been
      difficult to study due to its complex structure and regional variability.
      Measurement of cerebral cortex thickness at different disease stages may provide
      new insights into grey matter (GM) pathology. In the present investigation, we
      evaluated in vivo cortical thickness and its relationship to disability, disease
      duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution
      MRI brain scans were obtained in 20 patients with clinically definite multiple
      sclerosis and 15 age-matched normal subjects. A novel method of automated surface
      reconstruction yielded measurements of the cortical thickness for each subject's
      entire brain and computed cross-subject statistics based on the cortical anatomy.
      Statistical thickness difference maps were generated by performing t-tests
      between patient and control groups and individual thickness measures were
      submitted to analyses of variance to investigate the relationship between
      cortical thickness and clinical variables. The mean overall thickness of the
      cortical ribbon was reduced in multiple sclerosis patients compared with controls
      [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect
      of group (controls versus patients). In patients, we found significant main
      effects for disability, disease duration, T2 and T1 lesion volumes. The
      visualization of statistical difference maps of the cortical GM thickness on
      inflated brains across the cortical surface revealed a distinct distribution of
      significant focal thinning of the cerebral cortex in addition to the diffuse
      cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus
      2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)]
      brain regions was observed, even early in the course of the disease or in
      patients with mild disability. Patients with longstanding disease or severe
      disability, however, presented additionally with focal thinning of the motor
      cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in
      vivo measurement of cortical thickness is feasible in patients suffering from
      multiple sclerosis. The data provide new insight into the cortical pathology in
      multiple sclerosis patients, revealing focal cortical thinning beside an overall
      reduction of the cortical thickness with disease progression.

PMID- 12805101
TI  - Drug targeting by long-circulating liposomal glucocorticosteroids increases
      therapeutic efficacy in a model of multiple sclerosis.
AB  - High-dose glucocorticosteroid hormones are a mainstay in the treatment of
      relapses in multiple sclerosis. We searched for a way to deliver ultra high doses
      of glucocorticosteroids to the CNS of rats with experimental autoimmune
      encephalomyelitis (EAE) using a novel formulation of polyethylene glycol (PEG)
      coated long-circulating liposomes encapsulating prednisolone (predni solone
      liposomes, PL). 3H-labelled PL showed selective targeting to the inflamed CNS,
      where up to 4.5-fold higher radioactivity was achieved than in healthy control
      animals. HPLC revealed much higher and more persistent levels of prednisolone in
      spinal cord after PL compared with an equal dose of free prednisolone. Gold
      labelled liposomes could be detected in the target tissue, mostly taken up by
      macrophages (Mphi), microglial cells and astrocytes. Blood-brain barrier
      disruption was greatly reduced by 10 mg/kg PL, which was superior to a 5-fold
      higher dose of free methylprednisolone (MP). PL was also superior to MP in
      diminishing T-cell infiltration by induction of T-cell apoptosis in spinal cord.
      Mphi infiltration was clearly decreased only by PL. The percentage of tumour
      necrosis factor-alpha (TNF-alpha)-positive T cells or Mphi was greatly reduced by
      PL and by MP. No adverse effects on glial cells were detected. A single injection
      of PL clearly ameliorated the course of adoptive transfer EAE and EAE induced by
      immunization. In conclusion, PL is a highly effective drug in treatment of EAE,
      and is superior to a 5-fold higher dose of free MP, possibly by means of drug
      targeting. These findings may have implications for future therapy of autoimmune
      disorders such as multiple sclerosis.

PMID- 12805102
TI  - Exploring the neurological substrate of emotional and social intelligence.
AB  - The somatic marker hypothesis posits that deficits in emotional signalling
      (somatic states) lead to poor judgment in decision-making, especially in the
      personal and social realms. Similar to this hypothesis is the concept of
      emotional intelligence, which has been defined as an array of emotional and
      social abilities, competencies and skills that enable individuals to cope with
      daily demands and be more effective in their personal and social life. Patients
      with lesions to the ventromedial (VM) prefrontal cortex have defective somatic
      markers and tend to exercise poor judgment in decision-making, which is
      especially manifested in the disadvantageous choices they typically make in their
      personal lives and in the ways in which they relate with others. Furthermore,
      lesions to the amygdala or insular cortices, especially on the right side, also
      compromise somatic state activation and decision-making. This suggests that the
      VM, amygdala and insular regions are part of a neural system involved in somatic
      state activation and decision-making. We hypothesized that the severe impairment
      of these patients in real-life decision-making and an inability to cope
      effectively with environmental and social demands would be reflected in an
      abnormal level of emotional and social intelligence. Twelve patients with focal,
      stable bilateral lesions of the VM cortex or with right unilateral lesions of the
      amygdala or the right insular cortices, were tested on the Emotional Quotient
      Inventory (EQ-i), a standardized psychometric measure of various aspects of
      emotional and social intelligence. We also examined these patients with various
      other procedures designed to measure decision-making (the Gambling Task), social
      functioning, as well as personality changes and psychopathology; standardized
      neuropsychological tests were applied to assess their cognitive intelligence,
      executive functioning, perception and memory as well. Their results were compared
      with those of 11 patients with focal, stable lesions in structures outside the
      neural circuitry thought to mediate somatic state activation and decision-making.
      Only patients with lesions in the somatic marker circuitry revealed significantly
      low emotional intelligence and poor judgment in decision-making as well as
      disturbances in social functioning, in spite of normal levels of cognitive
      intelligence (IQ) and the absence of psychopathology based on DSM-IV criteria.
      The findings provide preliminary evidence suggesting that emotional and social
      intelligence is different from cognitive intelligence. We suggest, moreover, that
      the neural systems supporting somatic state activation and personal judgment in
      decision-making may overlap with critical components of a neural circuitry
      subserving emotional and social intelligence, independent of the neural system
      supporting cognitive intelligence.

PMID- 12805103
TI  - Neuroprotection by minocycline facilitates significant recovery from spinal cord
      injury in mice.
AB  - Acute spinal cord injury (SCI) produces tissue damage that continues to evolve
      days and weeks after the initial insult, with corresponding functional
      impairments. Reducing the extent of progressive tissue loss ('neuroprotection')
      following SCI should result in a better recovery from SCI, but treatment options
      have thus far been limited. In this study, we have tested the efficacy of
      minocycline in ameliorating damage following acute SCI in mice. This semi
      synthetic tetracycline antibiotic has been reported to inhibit the expression and
      activity of several mediators of tissue injury, including inflammatory cytokines,
      free radicals and matrix metalloproteinases, making it a suitable candidate for
      study. Mice were subjected to extradural compression of the spinal cord using a
      modified aneurysm clip, following which they received treatment with either
      minocycline or vehicle beginning 1 h after injury. Behavioural testing of
      hindlimb function was initiated 3 days after injury using the Basso Beattie
      Bresnahan locomotor rating scale, and at 1 week using the inclined plane test.
      Functional assessments demonstrated that minocycline administration significantly
      improved both hindlimb function and strength from 3 to 28 days after injury
      compared with vehicle controls. Furthermore, gross lesion size in the spinal cord
      was significantly reduced by minocycline, and there was evidence of axonal
      sparing as determined using fluorogold labelling of the rubrospinal tract and by
      Bielchowsky silver stain. Finally, a comparison of minocycline against the
      currently approved treatment for acute SCI in humans, methylprednisolone,
      demonstrated superior behavioural recovery in the minocycline-treated animals.

PMID- 12805104
TI  - Altered expression patterns of group I and II metabotropic glutamate receptors in
      multiple sclerosis.
AB  - Recent evidence supports a role for glutamate receptors in the pathophysiology of
      multiple sclerosis. In the present study, we have focused specifically on the
      expression of metabotropic glutamate receptors (mGluRs) in multiple sclerosis
      brain tissue. The expression of group I (mGluR1alpha and mGluR5) and group II
      (mGluR2/3) mGluRs was studied using immunohistochemistry in tissue from 12
      multiple sclerosis cases and seven non-neurological controls. The expression
      patterns of both group I and II mGluRs in multiple sclerosis tissue differed
      significantly from those in control tissue. Strong mGluR1alpha immunoreactivity
      was observed in axons of the subcortical white matter, particularly in the centre
      of actively demyelinating lesions and in the borders of chronic active lesions.
      mGluR1alpha axonal immunopositivity was also found in normal appearing multiple
      sclerosis white matter, but axons in control white matter were generally
      negative. mGluR1alpha axonal labelling was associated with the presence of non
      phosphorylated neurofilaments and beta-amyloid precursor protein, which are
      sensitive markers for axonal injury and disturbed axonal transport. Changes in
      mGluR immunoreactivity were also observed in glia. A diffuse increase in the
      expression of mGluR5 and mGluR2/3 was detected in reactive astrocytes in multiple
      sclerosis lesions. However, only a subpopulation of reactive astroglial cells
      expressed mGluR1alpha. In addition, labelling with antibodies to mGluR2/3 and, to
      a lesser extent labelling with antibodies to mGluR1alpha, was detected in a
      population of cells of the microglial/macrophage lineage that displayed a
      macrophage-like morphology. Our data suggest that mGluRs, like ionotropic
      glutamate receptors, play a role in the complex processes that are associated
      with the progressive brain damage in multiple sclerosis, including both glial
      activation and pathological changes in axons.

PMID- 12805105
TI  - Short and long latency afferent inhibition in Parkinson's disease.
AB  - Sensory abnormalities have been reported in Parkinson's disease and may
      contribute to the motor deficits. Peripheral sensory stimulation inhibits the
      motor cortex, and the effects depend on the interstimulus interval (ISI) between
      the sensory stimulus and transcranial magnetic stimulation (TMS) to the motor
      cortex. Short latency afferent inhibition (SAI) occurs at an ISI of approximately
      20 ms, and long latency afferent inhibition (LAI) at an ISI of approximately 200
      ms. We studied SAI and LAI in 10 Parkinson's disease patients with the aim of
      assessing whether sensorimotor processing is altered in Parkinson's disease.
      Patients were studied on and off medication, and the findings were compared with
      10 age-matched controls. Median nerve and middle finger stimulation were
      delivered 20-600 ms before TMS to the contralateral motor cortex. The motor
      evoked potentials were recorded from the relaxed first dorsal interosseous (FDI)
      muscle. SAI was normal in Parkinson's disease patients off dopaminergic
      medications, but it was reduced on the more affected side in Parkinson's disease
      patients on medication. LAI was reduced in Parkinson's disease patients compared
      with controls independent of their medication status. LAI reduced long interval
      intracortical inhibition in normal subjects but not in Parkinson's disease
      patients. The different results for SAI and LAI indicate that it is likely that
      separate mechanisms mediate these two forms of afferent inhibition. SAI probably
      represents the direct interaction of a sensory signal with the motor cortex. This
      pathway is unaffected by Parkinson's disease but is altered by dopaminergic
      medication in Parkinson's disease patients and may contribute to the side effects
      of dopaminergic drugs. LAI probably involves other pathways such as the basal
      ganglia or cortical association areas. This defective sensorimotor integration
      may be a non-dopaminergic manifestation of Parkinson's disease.

PMID- 12805107
TI  - Olfactory short-term memory and related amygdala recordings in patients with
      temporal lobe epilepsy.
AB  - Olfactory short-term recognition memory was assessed with a delayed odour
      matching task in 38 patients with unilateral temporal lobe epilepsy (TLE) and
      stereotactic electroencephalography (SEEG) recordings taken prior to surgical
      treatment. The amygdala SEEG activity associated with odorant stimulation was
      examined in 18 patients. Because the invasive SEEG procedure is only performed in
      a clinical framework, electrophysiological data obtained from these patients
      could not be analysed in comparison with data obtained from control subjects.
      Behavioural results (hits, false alarms, discrimination, bias scores) showed
      global impairment of odour recognition memory in patients when compared with
      controls. We also found lower discrimination and higher false alarm scores in
      left than in right TLE patients, and higher false alarm scores in male than in
      female patients. The hemisphere effect is discussed in terms of psychosocial
      trait differences between patients. Electrophysiological recordings collected
      from the amygdala demonstrated that odorant stimulation was associated with
      chemosensory evoked potentials (CSEPs). Analysis revealed that CSEPs obtained for
      target odorants had lower peak amplitudes and latencies than those obtained in
      response to sample odorants. The reduced peak amplitudes suggest a mechanism of
      repetition suppression--a process assumed to reflect neural activity related to
      high-level cognitive processes such as attention, memory and decision making.
      Latency modulations appear rather to be linked to early stages of information
      processing and may therefore reflect a facilitation process due to selective
      attention.

PMID- 12805106
TI  - Dopaminergic drug effects on physiological connectivity in a human cortico
      striato-thalamic system.
AB  - Cortico-striato-thalamic (CST) systems are anatomical substrates for many motor
      and executive functions and are implicated in diverse neuropsychiatric disorders.
      Electrophysiological studies in rats, monkeys and patients with Parkinson's
      disease have shown that power and coherence of low frequency oscillations in CST
      systems can be profoundly modulated by dopaminergic drugs. We combined functional
      MRI with correlational and path analyses to investigate functional and effective
      connectivity, respectively, of a prefronto-striato-thalamic system activated by
      object location learning in healthy elderly human subjects (n = 23; mean age = 72
      years). Participants were scanned in a repeated measures, randomized, placebo
      controlled design to measure modulation of physiological connectivity between CST
      regions following treatment with drugs which served both to decrease (sulpiride)
      and increase (methylphenidate) dopaminergic transmission, as well as non
      dopaminergic treatments (diazepam and scopolamine) to examine non-specific
      effects. Functional connectivity of caudate nucleus was modulated specifically by
      dopaminergic drugs, with opposing effects of sulpiride and methylphenidate. The
      more salient effect of sulpiride was to increase functional connectivity between
      caudate and both thalamus and ventral midbrain. A path diagram based on prior
      knowledge of unidirectional anatomical projections between CST components was
      fitted satisfactorily to the observed inter-regional covariance matrix. The
      effect of sulpiride was defined more specifically in the context of this model as
      increased strength of effective connection from ventral midbrain to caudate
      nucleus. In short, we have demonstrated enhanced functional and effective
      connectivity of human caudate nucleus following sulpiride treatment, which is
      compatible both with the anatomy of ascending dopaminergic projections and with
      electrophysiological studies indicating abnormal coherent oscillations of CST
      neurons in parkinsonian states.

PMID- 12805108
TI  - Abnormalities in hippocampi remote from the seizure focus: a T2 relaxometry
      study.
AB  - The aim of this study was to determine whether partial epilepsy is associated
      with abnormalities in hippocampi that are not the primary seizure focus. As
      hippocampal T2 relaxometry is useful for identifying abnormalities that are not
      obvious on visual assessment of MRI, this was the method employed. Of 457
      consecutive children and young adults from whom T2 relaxometry data were
      obtained, 96 had well characterized partial epilepsy and were enrolled, along
      with 27 control subjects. The patients were divided on the basis of clinical,
      video-EEG and visual MRI assessment into three groups: (i) those with temporal
      lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) (MTS-TLE); (ii) lesional
      TLE (l-TLE); or (iii) extratemporal epilepsy (ETE). There was a significant and
      similar prolongation of T2 relaxation time identified in hippocampi remote from
      the seizure focus in all patient groups when compared with control subjects. In
      the non-sclerotic hippocampus of patients with MTS, T2 relaxation time was
      prolonged by a mean of 3.3 ms [95% confidence interval (CI), 0.8-5.9 ms; P =
      0.01], patients with l-TLE had prolongation of T2 relaxation time by a mean of
      4.3 ms (95% CI, 1.8-7.1 ms; P = 0.001) and those with ETE had prolongation of T2
      relaxation time by a mean of 3.7 ms (95% CI, 1.6-6.6 ms; P = 0.006) compared with
      control subjects after adjustment for age. Unsurprisingly, in patients with MTS
      TLE, T2 relaxation time in the sclerotic hippocampus was prolonged by a mean of
      19 ms (95% CI = 14.6-22.4 ms; P < 0.001). The similarity in the extent of
      prolongation of T2 relaxation time in hippocampi that are not the primary
      epileptogenic focus, the wide variety of structural associations and the varied
      sites of epileptogenic foci, considered together, suggest that the abnormalities
      are likely to be caused by ongoing seizure activity rather than by underlying
      aetiology or site of epileptogenic focus.

PMID- 12805109
TI  - Changes in emotion after circumscribed surgical lesions of the orbitofrontal and
      cingulate cortices.
AB  - To analyse the functions of different parts of the prefrontal cortex in emotion,
      patients with different prefrontal surgical excisions were compared on four
      measures of emotion: voice and face emotional expression identification, social
      behaviour, and the subjective experience of emotion. Some patients with bilateral
      lesions of the orbitofrontal cortex (OFC) had deficits in voice and face
      expression identification, and the group had impairments in social behaviour and
      significant changes in their subjective emotional state. Some patients with
      unilateral damage restricted to the OFC also had deficits in voice expression
      identification, and the group did not have significant changes in social
      behaviour or in their subjective emotional state. Patients with unilateral
      lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or
      medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face
      expression identification, had some change in social behaviour, and had
      significant changes in their subjective emotional state. Patients with unilateral
      lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases,
      impaired on voice and face expression identification, had some changes in social
      behaviour, and had significant changes in their subjective emotional state.
      Patients with dorsolateral prefrontal cortex lesions or with medial lesions
      outside ACC and medial BA 9 areas (dorsolateral/other medial group) were
      unimpaired on any of these measures of emotion. In all cases in which voice
      expression identification was impaired, there were no deficits in control tests
      of the discrimination of unfamiliar voices and the recognition of environmental
      sounds. Thus bilateral or unilateral lesions circumscribed surgically within the
      OFC can impair emotional voice and/or face expression identification, but
      significant changes in social behaviour and in subjective emotional state are
      related to bilateral lesions. Importantly, unilateral lesions of the ACC
      (including some of medial BA 9) can produce voice and/or face expression
      identification deficits, and marked changes in subjective emotional state. These
      findings with surgically circumscribed lesions show that within the prefrontal
      cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of
      aspects of emotion in humans including emotion identification, social behaviour
      and subjective emotional state, and that the dorsolateral prefrontal areas are
      not involved in emotion in these ways.

PMID- 12805110
TI  - Enhanced activation of axonally transported stress-activated protein kinases in
      peripheral nerve in diabetic neuropathy is prevented by neurotrophin-3.
AB  - The objective was to determine whether stress-activated protein kinases (SAPKs)
      mediated the transfer of diabetes-induced stress signals from the periphery to
      somata of sensory neurons. Thus, we characterized axonal transport of SAPKs in
      peripheral nerve, studied any alteration in streptozotocin (STZ)-diabetic rats
      and examined effects of neurotrophin-3 (NT-3) on diabetes-induced events. We
      demonstrate that c-jun N-terminal kinase (JNK) and p38 are bidirectionally
      axonally transported at fast rates in sciatic nerve. In STZ-diabetic rats the
      relative levels of retrograde axonal transport of phosphorylated (activated) JNK
      and p38 were raised compared with age-matched controls (all data are in arbitrary
      units and expressed as fold increase over control: JNK 54-56 kDa isoforms,
      control 1.0 +/- 0.19, diabetic 2.5 +/- 0.26; p38, control 1.0 +/- 0.09, diabetic
      2.9 +/- 0.52; both P < 0.05). Transport of total enzyme levels of JNK and p38 and
      phosphorylated extracellular signal-regulated kinase (ERK) was not significantly
      altered and anterograde axonal transport of phosphorylated JNK and p38 was
      unaffected by diabetes. The transcription factor ATF-2, which is phosphorylated
      and activated by JNK and p38, also exhibited elevated retrograde axonal transport
      in STZ-diabetic animals (control 1.0 +/- 0.07, diabetic 3.0 +/- 0.41; P < 0.05).
      Treatment of STZ-diabetic animals with 5 mg/kg human recombinant NT-3 prevented
      activation of JNK and p38 in sciatic nerve (phosphorylated JNK, control 1.0 +/-
      0.09, diabetic 1.95 +/- 0.35, diabetic + NT-3 1.09 +/- 0.12; P < 0.05 diabetic
      versus others; phosphorylated p38, control 1.0 +/- 0.16, diabetic 4.7 +/- 0.9,
      diabetic + NT-3 1.19 +/- 0.18; P < 0.05 diabetic versus others). The results show
      that JNK and p38 are transported axonally and may mediate the transfer of
      diabetes-related stress signals, possibly triggered by loss of neurotrophic
      support, from the periphery to the neuronal soma.

PMID- 12805111
TI  - Changes in the expression and localization of the paranodal protein Caspr on
      axons in chronic multiple sclerosis.
AB  - The presence of intact paranodal junctions on myelinated axons in the CNS and PNS
      is crucial for both myelin sheath attachment and saltatory impulse conduction.
      The axonal glycoprotein contactin-associated protein (Caspr) is expressed in the
      paranodal region and plays an important role in the creation and maintenance of
      these adhesive junctions. In the present study, antibodies to Caspr were used to
      assess the integrity of paranodal junctions on myelinated axons in brain and
      spinal cord tissue from subjects with longstanding multiple sclerosis, a
      neurological disorder that affects both myelin and axons. Triple
      immunofluorescence combined with confocal laser scanning microscopy showed that
      axons in the demyelinated centre of the 36 brain and 16 spinal cord multiple
      sclerosis lesions studied were devoid of Caspr immunoreactivity, suggesting that
      axons down regulate the expression of Caspr following demyelination. Additional
      data indicated that Caspr reappears in the paranodal region with the formation of
      new myelin sheaths. Immuno labelling further revealed that Caspr on myelinated
      axons in border regions was often no longer concentrated in the paranodal region,
      but was also present in the internodal region-a phenomenon particularly common in
      the borders of the more chronic lesions in the collection. Myelinated axons with
      long Caspr-positive stretches were often present at a considerable distance from
      the lesion edges. These findings raise the possibility that the aberrant location
      of Caspr is an early sign of impending myelin loss. This would imply that
      demyelination continues at a slow rate in established lesions. The diameters of
      Caspr-positive structures on some myelinated axons near the lesion edges were
      also increased. Moreover, the gap between individual myelin sheaths on these
      apparently swollen axons was widened occasionally and a very small myelin sheath
      plus additional Caspr-positive structures had sometimes formed in the enlarged
      space. This finding thus suggests that the formation of new myelin in multiple
      sclerosis is not only induced following the loss of complete internodes but also
      in response to broadening of the nodal region. Interestingly, alterations in the
      expression and localization of Caspr were observed in tissue from both subjects
      with the primary and secondary progressive form of multiple sclerosis. In
      summary, the present study provides immunohistochemical evidence that paranodal
      junctions on some myelinated axons in the borders of lesions of patients with
      chronic progressive multiple sclerosis are no longer intact. This may impair
      saltatory impulse conduction and lead to further myelin loss, thereby
      contributing to disease progression in multiple sclerosis.

PMID- 12805112
TI  - Effects of visual deprivation on the organization of the semantic system.
AB  - Early onset blindness provides a lesion model to investigate whether experience
      dependent mechanisms subtend the functional anatomy of semantic retrieval. In
      particular, visual deprivation might alter the neural systems underlying
      retrieval of semantic information that is acquired via visual experience. Using
      functional MRI, we demonstrate that both early blind and sighted subjects
      activate a left-lateralized fronto-temporal 'core' semantic retrieval system and
      show common effects for retrieval of visually experienced semantic information.
      However, irrespective of the type of semantics, blind subjects activate
      additional extrastriate regions, which are coupled with frontal and temporal
      semantic regions. The resilience of semantic retrieval responses to visual
      deprivation suggests a considerable degree of innate and epigenetic specification
      of the semantic system. In contrast, the exuberant functional connectivity
      between extrastriate and 'core' semantic retrieval regions might be explained by
      abnormal pruning processes during early neurodevelopment.

PMID- 12805113
TI  - Abnormal sodium channel distribution in optic nerve axons in a model of
      inflammatory demyelination.
AB  - Myelinated fibres are characterized by the aggregation of Nav1.6 sodium channels
      within the axon membrane at nodes of Ranvier, where their presence supports
      saltatory conduction. In this study, we used immunocytochemical methods to study
      the organization of sodium channels along axons in experimental allergic
      encephalomyelitis (EAE), a model of multiple sclerosis. We studied axons within
      the optic nerve, a CNS tract commonly affected in multiple sclerosis, and their
      cell bodies of origin (retinal ganglion cells), using subtype-specific antibodies
      generated against sodium channel subtypes Nav1.1, Nav1.2, Nav1.3 and Nav1.6,
      which previously have been shown to be expressed by retinal ganglion cells. We
      demonstrate a significant switch from Nav1.6 to Nav1.2 expression in the optic
      nerve in EAE; there was a reduction in frequency of Nav1.6-positive nodes (84.5%
      Nav1.6-immunopositive nodes in control versus 32.9% in EAE) and increased
      frequency of Nav1.2-positive nodes (11.8% Nav1.2 immunopositive nodes in control
      versus 74.9% in EAE). Moreover, we observed a significant increase in the number
      of linear (presumably demyelinated) axonal profiles demonstrating extended
      diffuse immunostaining for Nav1.2 in EAE versus control optic nerves. These
      changes within the optic nerve are paralleled by decreased levels of Nav1.6 and
      increased Nav1.2 protein, together with increased levels of Nav1.2 mRNA, within
      retinal ganglion cells in EAE. Our findings of a loss of Nav1.6 and increased
      expression of Nav1.2 suggest that electrogenesis in EAE may revert to a stage
      similar to that observed in immature retinal ganglion cells in which Nav1.2
      channels support conduction of action potentials along axons.

PMID- 12805114
TI  - Huntington's disease-like phenotype due to trinucleotide repeat expansions in the
      TBP and JPH3 genes.
AB  - We report a group of 252 patients with a Huntington's disease-like (HDL)
      phenotype, including 60 with typical Huntington's disease, who had tested
      negative for pathological expansions in the IT15 gene, the major mutation in
      Huntington's disease. They were screened for repeat expansions in two other genes
      involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and
      prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between
      patients with HDL disease and autosomal dominant cerebellar ataxia or
      dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide
      repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and
      atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in
      the JPH3 gene. Two other patients had 44 and 46 CAA/CAG repeats in the TBP gene.
      Patients with expansions in the TBP or JPH3 genes had HDL phenotypes
      indistinguishable from Huntington's disease. Taking into account patients with
      typical Huntington's disease, their frequencies were evaluated as 3% each in our
      series of typical HDL patients. Interestingly, incomplete penetrance of the 46
      CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but
      healthy, parent. Furthermore, we report a new configuration of the expanded TBP
      allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in
      the DRPLA gene and insertions in the PRNP gene were not found in our group of
      patients. Further genetic heterogeneity of the HDL phenotype therefore exists.

PMID- 12805115
TI  - Pathology and physiology of auditory neuropathy with a novel mutation in the MPZ
      gene (Tyr145->Ser).
AB  - We studied a family with hereditary sensory motor neuropathy and deafness
      accompanying a missense mutation in the MPZ gene. Pathological examination of the
      cochlea in one of the family members revealed marked loss of auditory ganglion
      cells and central and peripheral auditory nerve fibres within the cochlea. The
      inner hair cells were of normal number with preserved morphology. The outer hair
      cells were normal in number except for a 30% reduction in just the apical turn.
      Examination of the sural nerve and the auditory nerve adjacent to the brainstem
      showed marked loss of fibres with evidence of incomplete remyelination of some of
      the remaining fibres. Studies of auditory function in surviving family members
      using electrophysiological and psychoacoustic methods provided evidence that the
      hearing deficits in this form of auditory neuropathy were probably related to a
      decrease of auditory nerve input accompanying axonal disease. Altered synchrony
      of discharge of the remaining fibres was a possible additional contributing
      factor.

PMID- 12805116
TI  - Aging affects the engagement of the hippocampus during autobiographical memory
      retrieval.
AB  - Surprisingly little is known about the neural correlates of remembering real life
      events in the context of normal aging. We therefore asked young and older adults
      to retrieve real life autobiographical event memories accrued over decades, while
      their brains were scanned using functional MRI. There were many commonalities
      between the groups in the wider network of brain areas active during retrieval.
      Nevertheless, one key difference emerged; while left hippocampal activation was
      apparent in the young, bilateral hippocampal activation was evident in older
      adults and direct comparison between the groups confirmed significantly greater
      right hippocampal activation in older adults. Notably, this difference was
      specific to autobiographical event memory retrieval, as the groups were
      comparable in the areas active during semantic memory retrieval. The present
      findings show that even when stimuli, tasks and performance appear
      indistinguishable between young and older adults, neural changes occur in aging
      with specificity in both the memory type and the brain regions affected. In
      particular, the results reveal that age-related effects are detectable in the
      hippocampus. This highlights the need to consider how the dynamic course of
      normal aging interacts with pathological processes that might also affect the
      hippocampus. Understanding this relationship may aid prognosis, as well as
      providing insights into plasticity in the anatomy of memory.

PMID- 12805118
TI  - Improved understanding of cortical injury by incorporating measures of functional
      anatomy.
AB  - Volume of injury is often used to describe a brain insult. However, this approach
      assumes cortical equivalency and ignores the special importance that certain
      cortical regions have in the generation of behaviour. We hypothesized that
      incorporating knowledge of normal brain functional anatomy into the description
      of a motor cortex injury would provide an improved framework for understanding
      consequent behavioural effects. Anatomical scanning was performed in 21 patients
      with a chronic cortical stroke that involved the sensorimotor cortex. Functional
      MRI (fMRI) was used to generate separate average activation maps for four tasks
      including hand, shoulder and face motor tasks in 14 controls. For each task,
      group average maps for contralateral sensorimotor cortex activation were
      generated. Injury to these maps was measured by superimposing each patient's
      infarct. These measurements were then correlated with behavioural assessments. In
      bivariate analyses, injury to fMRI maps correlated with behavioural assessments
      more strongly than total infarct volume. For example, performance on the Purdue
      pegboard test by the stroke-affected hand correlated with the fraction of hand
      motor map injured (r = -0.79) more strongly than with infarct volume (r = -0.60).
      In multiple linear regression analyses, measures of functional map injury, but
      not infarct volume, remained as significant explanatory variables for behavioural
      assessments. Injury to >37% of the hand motor map was associated with total loss
      of hand motor function. Hand and shoulder motor maps showed considerable spatial
      overlap (63%) and similar behavioural consequences of injury to each map, while
      hand and face motor maps showed limited overlap (10.4%) and disparate behavioural
      consequences of injury to each map. Lesion effects support current models of
      broad, rather than focal, sensorimotor cortex somatotopic representation. In the
      current cross-sectional study, incorporating an understanding of normal tissue
      function into lesion measurement provided improved insights into the behavioural
      consequences of focal brain injury.

PMID- 12805117
TI  - Different patterns of parasympathetic activation in uni- and bilateral
      migraineurs.
AB  - Several lines of evidence support involvement of the parasympathetic system in
      migraine: (i) migraine-associated symptoms, such as exaggerated facial flushing,
      lacrimation and rhinorrhea; (ii) increased levels of cranial venous vasoactive
      intestinal peptide in migraineurs during attacks; and (iii) reports of migraine
      pain alleviation by intranasal instillation of lidocaine, which can block some of
      the parasympathetic outflow to the cranium. This study assessed cranial
      parasympathetic function in migraineurs in between attacks, assuming that
      abnormal function might imply involvement of the parasympathetics in migraine
      pathogenesis. We tested 39 female migraineurs outside attacks, of whom 11 had
      bilateral pain, 20 unilateral at a specific side and eight alternating unilateral
      head pain, and 16 controls. The trigemino-parasympathetic reflex was studied,
      using soapy and saline eye drops for stimulation of the afferent limb of the
      reflex arch, and cutaneous vascular response at the forehead for the efferent
      limb. The latter was recorded by photoplethysmography on both sides of the
      forehead. We found no difference in vasodilatation between migraineurs as a group
      and controls (83.7 +/- 6.5% and 80.8 +/- 7.6%, respectively, not significant).
      However, when analysing data by the site of pain, we found that those with
      bilateral pain had the largest vasodilatation response (141.6 +/- 16.2%, P < 0.05
      versus controls, analysis of varance, post hoc Tukey-Kramer HSD), while those
      with unilateral pain had the least vasodilatation (45.5 +/- 3.3%, P < 0.05). The
      response of patients with alternating pain (97.2 +/- 12.6%) did not differ from
      controls. It is concluded that cranial parasympathetic function does differ among
      patients with various migraine types at rest. Based on the understanding of
      dysfunctional brainstem pain modulation in migraine, we suggest a model of within
      brainstem interaction between the two locus coeruleus nuclei, which are involved
      in control of pain and cranial parasympathetic outflow. The model assumes various
      levels of inhibitory inter-relationships between these two nuclei; diminution or
      absence of the normal reciprocal inhibitory relationships between them may
      underlie the augmented cranial parasympathetic response in bilateral migraineurs,
      while an excess of reciprocal inhibitory relationship between them may underlie
      the diminished cranial parasympathetic response in unilateral migraineurs. These
      findings might help in clarifying inter-relationships between brainstem nuclei in
      the context of migraine pathogenesis.

PMID- 12805119
TI  - Clinical and neuroinflammatory responses to meningoencephalitis in substance P
      receptor knockout mice.
AB  - Human African trypanosomiasis, also known as sleeping sickness, affects the CNS
      at the late stage of the disease. Untreated the disease is invariably fatal, and
      melarsoprol, the only available and effective treatment for CNS disease, is
      associated in up to 10% of cases with a severe post-treatment reactive
      encephalopathy (PTRE), which can itself cause death. We used a reproducible mouse
      model of the PTRE to investigate the pathogenesis and treatment of this
      condition. Mice infected with Trypanosoma brucei brucei and treated subcuratively
      with diminazene aceturate develop a severe meningoencephalitis that closely
      resembles PTRE. We previously reported that substance P plays an important role
      in PTRE. We investigated the effect of disrupting the gene encoding for the NK1
      receptor in mice on the clinical and neuroinflammatory response in this model.
      After induction of PTRE, NK1-/- mice showed a significant reduction in clinical
      impairment compared with NK1+/+ mice, but the severity of the neuroinflammatory
      response was significantly greater in NK1-/- mice. To explore the mechanisms of
      this dissociated phenotype, we treated infected NK1-/- mice with antagonists to
      NK2 and NK3 receptors, either singly or in combination. While none of these
      antagonist treatments altered the clinical score, combined treatment with the NK2
      and NK3 antagonists significantly reduced the neuroinflammatory grading score in
      the NK1-/- mice. Thus, the clinical and neuroinflammatory responses to parasite
      invasion can be mediated by different pathways, and, importantly, the
      neuroinflammatory response is altered by alternative tachykinin receptor usage.
      These findings could be exploited to develop novel anti-inflammatory therapies in
      Human African trypanosomiasis by modulating the NK1 receptor as well as the
      parasite.

PMID- 12805120
TI  - A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core
      like lesions.
AB  - Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle
      weakness and the presence of nemaline rods. Five genes have now been associated
      with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin
      (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1). In addition, mutations in
      the ryanodine receptor gene (RYR1) have been associated with core-rod myopathy.
      Here we report linkage in two unrelated families, with a variant of nemaline
      myopathy, with associated core-like lesions. The clinical phenotype consists of
      muscle weakness in addition to a peculiar kind of muscle slowness. A genome-wide
      scan revealed a locus for nemaline myopathy with core-like lesions on chromosome
      15q21-q23 for both families. Combining the two families gave a two-point LOD
      score of 10.65 for D15S993. The alpha-tropomyosin-1 gene (TPM1) located within
      this region is the strongest candidate gene. However, no mutations were found in
      the protein-coding region of TPM1, although small deletions or mutations in an
      intron cannot be excluded. The critical region contains few other candidate genes
      coding for muscle proteins and several genes of unknown function, and has not yet
      been sequenced completely. The novel phenotype of nemaline myopathy in the two
      presented families corresponds to an also novel, as yet uncharacterized,
      genotype.

PMID- 12805121
TI  - Inverse U-shaped curve for age dependency of torsional eye movement responses to
      galvanic vestibular stimulation.
AB  - To investigate age dependent changes we analysed torsional eye movement responses
      to binaural and monaural galvanic vestibular stimulation (GVS) in 57 healthy
      subjects (20-69 years old). GVS (1-3 mA) induced torsional eye movements
      consisting of static torsion toward the anode (amplitude 1-6 degrees ) and
      superimposed torsional nystagmus (slow phase velocity 0.5-3 degrees /s, quick
      phase amplitude 0.5-2 degrees, nystagmus frequency 0.75-1.5 s-1). Static ocular
      torsion and torsional nystagmus increased from the third to the sixth decade and
      decreased in older subjects, e.g. slow phase velocity increased from 1.5 degrees
      /s (20-29 years) to 2.9 degrees /s (50-59 years) and decreased to 2.5 degrees /s
      for the seventh decade (60-69 years). Thus, an inverse U-shaped curve was found
      for the dependence of torsional eye movement responses on age. All structures
      relevant for vestibular function degenerate with age, but at varying times. Since
      hair cell loss precedes those seen in the vestibular nerve and Scarpa's ganglion,
      the decrease in hair cell counts could be compensated for by increased
      sensitivity of afferent nerve fibres or central mechanisms. Increased sensitivity
      could thus maintain normal function despite reduced peripheral input. As GVS acts
      at the vestibular nerve (thereby bypassing the hair cells), electrical
      stimulation should be more efficient in subjects with the beginning of hair cell
      degeneration, as seen in our data up to the sixth decade. The degeneration of
      nerve fibres, ganglion cells and central neurons becomes evident at older ages.
      Thus, the compensatory increase in sensitivity breaks down and GVS-induced eye
      movements decline-a finding that is reflected by the inverse U-shaped curve for
      age dependency presented in this study.

PMID- 12805122
TI  - Cortical correlates of vestibulo-ocular reflex modulation: a PET study.
AB  - To elucidate cortical correlates of vestibulo-ocular reflex (VOR) modulation, we
      observed cortical activation during fixation suppression and habituation of
      caloric vestibular nystagmus in 12 normal subjects, using PET. Significant
      positive correlation between regional cerebral blood flow (rCBF) and slow phase
      eye velocity of caloric nystagmus was observed in the middle and posterior
      insula, inferior parietal lobule, temporal pole, right fusiform gyrus, lingual
      gyrus, and cerebellar vermis and hemisphere. The rCBF increase in the insular
      region and the inferior parietal lobule was lateralized depending on the
      direction of the nystagmus. Caloric nystagmus was suppressed as a result of
      visual fixation, during which time the area around the right frontal eye field,
      temporal pole, inferior temporal gyrus, a broad area in the visual cortex,
      including fusiform and lingual gyrus, cerebellar uvula/nodulus and flocculus,
      exhibited positive correlation with fixation suppression of caloric nystagmus,
      while vestibular cortices exhibited negative correlation. The caloric nystagmus
      habituated with repetition of stimulation. With habituation, we observed
      activation in the right anterior cingulate gyrus, left superior parietal lobule
      and right cuneus, and deactivation in the anterior insula, cingulate gyrus,
      inferior parietal lobule and occipito-temporal visual cortex. The region that
      showed significant co-activation with fixation suppression and habituation of
      caloric nystagmus was the right cuneus, and significant co-deactivation was
      observed in the anterior insula, cingulate gyrus, inferior parietal lobule and
      middle temporal visual cortex. The present results support previous observations
      that the parieto-insular cortex and inferior parietal lobule are involved in
      processing of vestibular information, and, in addition, suggest that activation
      may depend on the direction of nystagmus. Deactivation of vestibular cortices
      during visual fixation supports the concept of inhibitory visual-vestibular
      interaction in the cortex. Significant activation of the cingulate, superior
      parietal and visual cortices, and cerebellar vermis accompanying reduction of
      caloric response with repeated stimuli suggests possible involvement of these
      regions in vestibular habituation. Common activation of the cuneus in visual
      cortex and deactivation of vestibular and visuo-spatial association cortices by
      both visual suppression and habituation of VOR suggests that these two mechanisms
      are not completely independent but may share some cortical and subcortical
      regions.

PMID- 12805123
TI  - Neuroanatomical correlates of brainstem coma.
AB  - The brainstem tegmentum, including the reticular formation, contains distinct
      nuclei, each of which has a set of chemical, physiological and anatomical
      features. Damage to the brainstem tegmentum is known to cause coma, the most
      radical disturbance of consciousness. However, it has remained unclear which
      nuclei within the tegmentum are crucial for the maintenance of consciousness in
      humans. Accordingly, we initiated a retrospective study of MRIs obtained from 47
      patients with brainstem stroke. The lesion boundaries were charted on patient
      MRIs and transferred onto a corresponding series of 4.7 T MRIs obtained from a
      control brainstem specimen that later was cut on a freezing microtome and
      analysed histologically. In addition, medical charts and available post-mortem
      materials were used to obtain relevant clinical and anatomical data to verify the
      MRI readings in each case. We found that in the 38 patients who did not have
      coma, brainstem damage either was located outside the tegmentum (n = 29) or
      produced a very small and unilateral compromise of the tegmentum (n = 9). In
      contrast, in patients who had coma (n = 9), the lesions in the tegmentum were
      mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in
      the upper pons and the midbrain (n = 5). The maximum overlap territory of the
      lesions coincided with the location of the rostral raphe complex, locus
      coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial
      nucleus and the white matter in between these nuclei. We also found that four
      coma subjects developed hyperthermia and died in the absence of any infections.
      In these cases, the maximum lesion overlap was centred in the core of pontine
      tegmentum. Our findings suggest that lesions confined to the upper pons can cause
      coma in humans even in the absence of damage to the midbrain. The findings also
      point to the brainstem nuclei whose lesions are likely to be associated with loss
      of consciousness and fatal hyperthermia in humans.

PMID- 12805124
TI  - Impaired fibrinolysis in multiple sclerosis: a role for tissue plasminogen
      activator inhibitors.
AB  - Tissue plasminogen activator (tPA), a neuronal as well as the key fibrinolytic
      enzyme, is found concentrated on demyelinated axons in multiple sclerosis lesions
      together with fibrin(ogen) deposits. The decreased tPA activity in normal
      appearing white and grey matter and lesions of multiple sclerosis is reflected in
      diminished fibrinolysis as measured by a clot lysis assay. Nonetheless, peptide
      products of fibrin, including D-dimer, accumulate on demyelinated axons-the
      result of fibrinogen entry through a compromised blood-brain barrier (BBB).
      Analysis of tissue samples on reducing and non-reducing polyacrylamide gels
      demonstrates complexes of tPA with plasminogen activator inhibitor-1 (PAI-1) but
      not with neuroserpin, a tPA-specific inhibitor concentrated in grey matter. As
      total tPA protein remains unchanged in acute lesions and the concentration of PAI
      1 rises several fold, complex formation is a probable cause of the impaired
      fibrinolysis. Although the tPA-plasmin cascade promotes neurodegeneration in
      excitotoxin-induced neuronal death, in inflammatory conditions with BBB
      disruption it has been demonstrated to have a protective role in removing fibrin,
      which exacerbates axonal injury. The impaired fibrinolytic capacity resulting
      from increased PAI-1 synthesis and complex formation with tPA, which is
      detectable prior to lesion formation, therefore has the potential to contribute
      to axonal damage in multiple sclerosis.

PMID- 12805125
TI  - Saddle up, partner.

PMID- 12805126
TI  - Patients are experts in their own field.

PMID- 12805127
TI  - Just how demanding can we get before we blow it?

PMID- 12805128
TI  - Boosting performance measure for measure.

PMID- 12805129
TI  - Expert patients usher in a new era of opportunity for the NHS.

PMID- 12805130
TI  - Killing the goose that laid the golden egg?

PMID- 12805131
TI  - Patients will be reminded of appointments by text messages.

PMID- 12805132
TI  - England is in a sexual health crisis, MPs say.

PMID- 12805133
TI  - Arsenal helps publicise testicular cancer website.

PMID- 12805134
TI  - Paroxetine must not be given to patients under 18.

PMID- 12805136
TI  - What patients want from their doctors.

PMID- 12805138
TI  - Coroners will deliver fuller verdicts after inquests.

PMID- 12805139
TI  - EU health ministers reject proposal for limited direct to consumer advertising.

PMID- 12805140
TI  - New Zealand GPs call for end to direct to consumer advertising.

PMID- 12805141
TI  - India's burden of waterborne diseases is underestimated.

PMID- 12805142
TI  - Survival after partial lung transplants is as good as after full lung
      transplants.

PMID- 12805143
TI  - WHO investigates China's fall in SARS cases.

PMID- 12805147
TI  - Haemophilia patients launch action against Bayer over contaminated blood
      products.

PMID- 12805148
TI  - Make the most of your doctor.

PMID- 12805150
TI  - Wife wins case against GPs who did not disclose husband's HIV status.

PMID- 12805154
TI  - Drug companies want to inform patients.

PMID- 12805155
TI  - Man and superman. Interview by Lynn Eaton.

PMID- 12805156
TI  - Brandy, bridge, and other patient dilemmas.

PMID- 12805158
TI  - Seen and not heard. Interviewed by Sanjay Kumar.

PMID- 12805157
TI  - I am a good patient, believe it or not.

PMID- 12805159
TI  - Public health and company wealth.

PMID- 12805160
TI  - The most pressing problem of our age.

PMID- 12805161
TI  - Time to deliver with dignity.

PMID- 12805162
TI  - Letter from America.

PMID- 12805163
TI  - Should drug companies be allowed to talk directly to patients? YES.

PMID- 12805164
TI  - Should drug companies be allowed to talk directly to patients? NO.

PMID- 12805165
TI  - Cultural revolution.

PMID- 12805166
TI  - Do patients need to read research?

PMID- 12805167
TI  - Effects of educational interventions for self management of asthma in children
      and adolescents: systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the effectiveness of educational programmes for the self
      management of asthma in children and adolescents. DATA SOURCES: Databases of the
      Cochrane Airways Group, PsychINFO, reference lists of review papers, and eligible
      studies. REVIEW METHODS: Eligible studies were published randomised controlled
      trials or controlled clinical trials of educational programmes for the self
      management of asthma in children and adolescents that reported lung function,
      morbidity, self perception of asthma control, or utilisation of healthcare
      services. Eligible studies were abstracted, assessed for methodological quality,
      and pooled with fixed effects and random effects models. RESULTS: 32 of 45
      identified trials were eligible, totalling 3706 patients aged 2 to 18 years.
      Education in asthma was associated with improved lung function (standardised mean
      difference 0.50, 95% confidence interval 0.25 to 0.75) and self efficacy (0.36,
      0.15 to 0.57) and reduced absenteeism from school (-0.14, -0.23 to -0.04), number
      of days of restricted activity (-0.29, -0.33 to -0.09), and number of visits to
      an emergency department (-0.21, -0.33 to -0.09). When pooled by the fixed effects
      model but not by the random effects model, education was also associated with a
      reduced number of nights disturbed by asthma. The effect on morbidity was
      greatest among programmes with strategies based on peak flow, interventions
      targeted at the individual, and participants with severe asthma. CONCLUSIONS:
      Educational programmes for the self management of asthma in children and
      adolescents improve lung function and feelings of self control, reduce
      absenteeism from school, number of days with restricted activity, number of
      visits to an emergency department, and possibly number of disturbed nights.
      Educational programmes should be considered a part of the routine care of young
      people with asthma.

PMID- 12805168
TI  - How important is personal care in general practice?
AB  - OBJECTIVES: To explore patients' perceptions of the features of personal care and
      how far these are shared by healthcare providers; whether a continuing
      relationship between a health professional and a patient is essential for
      personal care; and the circumstances in which a continuing relationship is
      important. DESIGN: Qualitative analysis of semistructured interviews using the
      "framework" approach. SETTING: Six general practices in Leicestershire.
      PARTICIPANTS: 40 patients aged > or = 18 years, 13 general practitioners, 10
      practice and community nurses, and six practice administrative staff, recruited
      through participating practices. RESULTS: Patients' and healthcare providers'
      accounts cited human communication, individualised treatment or management, and
      whole person care as features of personal care. Personal care was described in
      three different contexts-a continuing relationship, a single consultation, and
      from the practice as a whole. The extent to which a continuing relationship was
      important for personal care was determined by the reason for consulting, as well
      as patients' consulting history and lifestyle. CONCLUSIONS: Patients, general
      practitioners, primary care nurses, and administrative staff hold similar views
      on the meaning of personal care, despite differences of emphasis reflecting their
      different roles. Personal care is promoted by but not always dependent on a
      continuing provider-patient relationship; human communication and individualised
      care emerged as important in making care personal whatever the context. Most
      respondents valued relationships in primary care and had clear ideas about when
      care in the context of a relationship was most valuable.

PMID- 12805169
TI  - Patient's response to the research.

PMID- 12805170
TI  - Patient's response to the research.

PMID- 12805171
TI  - Patients' views about taking antihypertensive drugs: questionnaire study.

PMID- 12805172
TI  - Patients' accounts of being removed from their general practitioner's list:
      qualitative study.
AB  - OBJECTIVE: To explore patients' accounts of being removed from a general
      practitioner's list. DESIGN: Qualitative analysis of semistructured interviews.
      SETTING: Patients' homes in Leicestershire. PARTICIPANTS: 28 patients who had
      recently been removed from a general practitioner's list. RESULTS: The removed
      patients gave an account of themselves as having genuine illnesses needing
      medical care. In putting their case that their removal was unjustified, patients
      were concerned to show that they were "good" patients who complied with the rules
      that they understood to govern the doctor-patient relationship: they tried to
      cope with their illness and follow medical advice, used general practice services
      "appropriately," were uncomplaining, and were polite with doctors. Removed
      patients also used their accounts to characterise the removing general
      practitioner as one who broke the lay rules of the doctor-patient relationship.
      These "bad" general practitioners were rude, impersonal, uncaring, and clinically
      incompetent and lied to patients. Patients felt very threatened by being removed
      from their general practitioner's list; they experienced removal as an attack on
      their right to be an NHS patient, as deeply distressing, and as stigmatising.
      CONCLUSIONS: Removal is an overwhelmingly negative and distressing experience for
      patients. Many of the problems encountered by removed patients may be remediable
      through general practices having an explicit policy on removal and procedures in
      place to help with "difficult" patients.

PMID- 12805173
TI  - Patients' accounts of being removed from their general practitioner's list:
      qualitative study. Patient's response to the research.

PMID- 12805174
TI  - Patients' accounts of being removed from their general practitioner's list:
      qualitative study. Patient's response to the research.

PMID- 12805175
TI  - Integrative approaches to pain management: how to get the best of both worlds.

PMID- 12805176
TI  - Managing pain.

PMID- 12805177
TI  - Time for a fresh look at complementary medicine.

PMID- 12805178
TI  - Multiple sclerosis. Interview by Harriet Gaze.

PMID- 12805179
TI  - Depression. Interview by Helen Crane.

PMID- 12805180
TI  - Diabetes. Interview by Paul Smith.

PMID- 12805181
TI  - Please don't touch me there: the ethics of intimate examinations: what
      examination is not intimate?

PMID- 12805182
TI  - Please don't touch me there: the ethics of intimate examinations: informed
      consent failed to protect me.

PMID- 12805183
TI  - Please don't touch me there: the ethics of intimate examinations: consent is
      crucial--but don't go too far, for students' and patients' sakes.

PMID- 12805184
TI  - Please don't touch me there: the ethics of intimate examinations: integrated
      approach to teaching and learning clinical skills.

PMID- 12805186
TI  - Please don't touch me there: the ethics of intimate examinations: how medical
      students are being taught at University of Antwerp.

PMID- 12805187
TI  - Patients' charities often lack cash.

PMID- 12805188
TI  - Shocked by attitude to MRSA.

PMID- 12805189
TI  - ATAC trial: reporting interim results is not helpful.

PMID- 12805190
TI  - Involving patients in a primary care research meeting worked well.

PMID- 12805191
TI  - 'Copying letters to patients is coming to a clinic near you'.

PMID- 12805192
TI  - 'Having a diagnosis is a qualification for the job'.

PMID- 12805193
TI  - 'The focus is on patients' clinical needs and distress'.

PMID- 12805194
TI  - 'We must accept that health care is a risky business'.

PMID- 12805195
TI  - 'You matter to the last moment of your life'.

PMID- 12805196
TI  - 'This added to my multiple myopia'.

PMID- 12805197
TI  - 'Both sides need to keep the relationship going'.

PMID- 12805198
TI  - The whole truth?

PMID- 12805199
TI  - The lowdown on international recruitment. Interview by Rhona MacDonald.

PMID- 12805200
TI  - Getting serious about SAS doctors.

PMID- 12805203
TI  - Mechanisms of activation, inhibition and specificity: crystal structures of the
      NMDA receptor NR1 ligand-binding core.
AB  - Excitatory neurotransmission mediated by the N-methyl-D-aspartate subtype of
      ionotropic glutamate receptors is fundamental to the development and function of
      the mammalian central nervous system. NMDA receptors require both glycine and
      glutamate for activation with NR1 and NR2 forming glycine and glutamate sites,
      respectively. Mechanisms to describe agonist and antagonist binding, and
      activation and desensitization of NMDA receptors have been hampered by the lack
      of high-resolution structures. Here, we describe the cocrystal structures of the
      NR1 S1S2 ligand-binding core with the agonists glycine and D-serine (DS), the
      partial agonist D-cycloserine (DCS) and the antagonist 5,7-dichlorokynurenic acid
      (DCKA). The cleft of the S1S2 'clamshell' is open in the presence of the
      antagonist DCKA and closed in the glycine, DS and DCS complexes. In addition, the
      NR1 S1S2 structure reveals the fold and interactions of loop 1, a cysteine-rich
      region implicated in intersubunit allostery.

PMID- 12805204
TI  - Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a
      general model for retroviral capsid assembly.
AB  - Although retroviruses from different genera form morphologically distinct
      capsids, we have proposed that all of these structures are composed of similar
      hexameric arrays of capsid (CA) protein subunits and that their distinct
      morphologies reflect different distributions of pentameric declinations that
      allow the structures to close. Consistent with this model, CA proteins from both
      HIV-1 and Rous sarcoma virus (RSV) form similar hexagonal lattices. However,
      recent structural studies have suggested that the Moloney murine leukemia virus
      (M-MuLV) CA protein may assemble differently. We now report an independent three
      dimensional reconstruction of two-dimensional crystals of M-MuLV CA. This new
      reconstruction reveals a hexameric lattice that is similar to those formed by HIV
      1 and RSV CA, supporting a generalized model for retroviral capsid assembly.

PMID- 12805205
TI  - Molecular architecture of the ATP-dependent CodWX protease having an N-terminal
      serine active site.
AB  - CodWX in Bacillus subtilis is an ATP-dependent, N-terminal serine protease,
      consisting of CodW peptidase and CodX ATPase. Here we show that CodWX is an
      alkaline protease and has a distinct molecular architecture. ATP hydrolysis is
      required for the formation of the CodWX complex and thus for its proteolytic
      function. Remarkably, CodX has a 'spool-like' structure that is formed by
      interaction of the intermediate domains of two hexameric or heptameric rings. In
      the CodWX complex, CodW consisting of two stacked hexameric rings (WW) binds to
      either or both ends of a CodX double ring (XX), forming asymmetric (WWXX) or
      symmetric cylindrical particles (WWXXWW). CodWX can also form an elongated
      particle, in which an additional CodX double ring is bound to the symmetric
      particle (WWXXWWXX). In addition, CodWX is capable of degrading EzrA, an
      inhibitor of FtsZ ring formation, implicating it in the regulation of cell
      division. Thus, CodWX appears to constitute a new type of protease that is
      distinct from other ATP-dependent proteases in its structure and proteolytic
      mechanism.

PMID- 12805206
TI  - Identification of residues contributing to the ATP binding site of Kir6.2.
AB  - The ATP-sensitive potassium (K(ATP)) channel links cell metabolism to membrane
      excitability. Intracellular ATP inhibits channel activity by binding to the
      Kir6.2 subunit of the channel, but the ATP binding site is unknown. Using
      cysteine-scanning mutagenesis and charged thiol-modifying reagents, we identified
      two amino acids in Kir6.2 that appear to interact directly with ATP: R50 in the N
      terminus, and K185 in the C-terminus. The ATP sensitivity of the R50C and K185C
      mutant channels was increased by a positively charged thiol reagent (MTSEA), and
      was reduced by the negatively charged reagent MTSES. Comparison of the inhibitory
      effects of ATP, ADP and AMP after thiol modification suggests that K185 interacts
      primarily with the beta-phosphate, and R50 with the gamma-phosphate, of ATP. A
      molecular model of the C-terminus of Kir6.2 (based on the crystal structure of
      Kir3.1) was constructed and automated docking was used to identify residues
      interacting with ATP. These results support the idea that K185 interacts with the
      beta-phosphate of ATP. Thus both N- and C-termini may contribute to the ATP
      binding site.

PMID- 12805207
TI  - Truncated product of the bifunctional DLST gene involved in biogenesis of the
      respiratory chain.
AB  - Dihydrolipoamide succinyltransferase (DLST) is a subunit enzyme of the alpha
      ketoglutarate dehydrogenase complex of the Krebs cycle. While studying how the
      DLST genotype contributes to the pathogenesis of Alzheimer's disease (AD), we
      found a novel mRNA that is transcribed starting from intron 7 in the DLST gene.
      The novel mRNA level in the brain of AD patients was significantly lower than
      that of controls. The truncated gene product (designated MIRTD) localized to the
      intermembrane space of mitochondria. To investigate the function of MIRTD, we
      established human neuroblastoma SH-SY5Y cells expressing a maxizyme, a kind of
      ribozyme, that specifically digests the MIRTD mRNA. The expression of the
      maxizyme specifically eliminated the MIRTD protein and the resultant MIRTD
      deficient cells exhibited a marked decrease in the amounts of subunits of
      complexes I and IV of the mitochondrial respiratory chain, resulting in a decline
      of activity. A pulse-label experiment revealed that the loss of the subunits is a
      post-translational event. Thus, the DLST gene is bifunctional and MIRTD
      transcribed from the gene contributes to the biogenesis of the mitochondrial
      respiratory complexes.

PMID- 12805208
TI  - Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in
      the male germline.
AB  - The mammalian polypyrimidine-tract binding protein (PTB), which is a
      heterogeneous ribonucleoprotein, is ubiquitously expressed. Unexpectedly, we
      found that, in Drosophila melanogaster, the abundant PTB transcript is present
      only in males (third instar larval, pupal and adult stages) and in adult flies is
      restricted to the germline. Most importantly, a signal from the somatic sex
      determination pathway that is dependent on the male-specific isoform of the
      doublesex protein (DSX(M)) regulates PTB, providing evidence for the necessity of
      soma-germline communication in the differentiation of the male germline. Analysis
      of a P-element insertion directly links PTB function with male fertility.
      Specifically, loss of dmPTB affects spermatid differentiation, resulting in the
      accumulation of cysts with elongated spermatids without producing fully separated
      motile sperms. This male-specific expression of PTB is conserved in D.virilis.
      Thus, PTB appears to be a particularly potent downstream target of the sex
      determination pathway in the male germline, since it can regulate multiple mRNAs.

PMID- 12805209
TI  - Survivin is required for a sustained spindle checkpoint arrest in response to
      lack of tension.
AB  - Genetic evidence is mounting that survivin plays a crucial role in mitosis, but
      its exact role in human cell division remains elusive. We show that mammalian
      cells lacking survivin are unable to align their chromosomes, fail to recruit
      Aurora B to kinetochores and become polyploid at a very high frequency. Survivin
      depleted cells enter mitosis with normal kinetics, but are delayed in
      prometaphase in a BubR1/Mad2-dependent fashion. Nonetheless, these cells exit
      mitosis prior to completion of chromosome congression and without sister
      chromatid segregation, indicating that the spindle assembly checkpoint is not
      fully functional. Indeed, in survivin-depleted cells, BubR1 and Mad2 are
      prematurely displaced from kinetochores, yet no tension is generated at
      kinetochores. Importantly, these cells fail to respond to drugs that prevent
      tension, but do arrest in mitosis after depolymerization of the mitotic spindle.
      This demonstrates that survivin is not required for initial checkpoint
      activation, or for sustained checkpoint activation by loss of microtubules.
      However, stable association of BubR1 to kinetochores and sustained checkpoint
      signalling in response to lack of tension crucially depend on survivin.

PMID- 12805210
TI  - Role of calnexin in the glycan-independent quality control of proteolipid
      protein.
AB  - The endoplasmic (ER) quality control apparatus ensures that misfolded or
      unassembled proteins are not deployed within the cell, but are retained in the ER
      and degraded. A glycoprotein-specific system involving the ER lectins calnexin
      and calreticulin is well documented, but very little is known about mechanisms
      that may operate for non-glycosylated proteins. We have used a folding mutant of
      a non- glycosylated membrane protein, proteolipid protein (PLP), to examine the
      quality control of this class of polypeptide. We find that calnexin associates
      with newly synthesized PLP molecules, binding stably to misfolded PLP. Calnexin
      also binds stably to an isolated transmembrane domain of PLP, suggesting that
      this chaperone is able to monitor the folding and assembly of domains within the
      ER membrane. Notably, this glycan-independent interaction with calnexin
      significantly retards the degradation of misfolded PLP. We propose that calnexin
      contributes to the quality control of non-glycosylated polytopic membrane
      proteins by binding to misfolded or unassembled transmembrane domains, and
      discuss our findings in relation to the role of calnexin in the degradation of
      misfolded proteins.

PMID- 12805211
TI  - The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin,
      ExoU.
AB  - Pseudomonas aeruginosa delivers the toxin ExoU to eukaryotic cells via a type III
      secretion system. Intoxication with ExoU is associated with lung injury,
      bacterial dissemination and sepsis in animal model and human infections. To
      search for ExoU targets in a genetically tractable system, we used controlled
      expression of the toxin in Saccharomyces cerevisiae. ExoU was cytotoxic for yeast
      and caused a vacuolar fragmentation phenotype. Inhibitors of human calcium
      independent (iPLA(2)) and cytosolic phospholipase A(2) (cPLA(2)) lipase activity
      reduce the cytotoxicity of ExoU. The catalytic domains of patatin, iPLA(2) and
      cPLA(2) align or are similar to ExoU sequences. Site-specific mutagenesis of
      predicted catalytic residues (ExoUS142A or ExoUD344A) eliminated toxicity. ExoU
      expression in yeast resulted in an accumulation of free palmitic acid, changes in
      the phospholipid profiles and reduction of radiolabeled neutral lipids. ExoUS142A
      and ExoUD344A expressed in yeast failed to release palmitic acid. Recombinant
      ExoU demonstrated lipase activity in vitro, but only in the presence of a yeast
      extract. From these data we conclude that ExoU is a lipase that requires
      activation or modification by eukaryotic factors.

PMID- 12805212
TI  - Tic40, a membrane-anchored co-chaperone homolog in the chloroplast protein
      translocon.
AB  - The function of Tic40 during chloroplast protein import was investigated. Tic40
      is an inner envelope membrane protein with a large hydrophilic domain located in
      the stroma. Arabidopsis null mutants of the atTic40 gene were very pale green and
      grew slowly but were not seedling lethal. Isolated mutant chloroplasts imported
      precursor proteins at a lower rate than wild-type chloroplasts. Mutant
      chloroplasts were normal in allowing binding of precursor proteins. However,
      during subsequent translocation across the inner membrane, fewer precursors were
      translocated and more precursors were released from the mutant chloroplasts.
      Cross-linking experiments demonstrated that Tic40 was part of the translocon
      complex and functioned at the same stage of import as Tic110 and Hsp93, a member
      of the Hsp100 family of molecular chaperones. Tertiary structure prediction and
      immunological studies indicated that the C-terminal portion of Tic40 contains a
      TPR domain followed by a domain with sequence similarity to co-chaperones
      Sti1p/Hop and Hip. We propose that Tic40 functions as a co-chaperone in the
      stromal chaperone complex that facilitates protein translocation across the inner
      membrane.

PMID- 12805213
TI  - Phospholipase Cdelta1 is required for skin stem cell lineage commitment.
AB  - Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in
      phosphoinositide turnover and is involved in a variety of physiological
      functions. Here we report that PLCdelta(1)-deficient mice undergo progressive
      hair loss in the first postnatal hair cycle. Epidermal hyperplasia was observed,
      and many hairs in the skin of PLCdelta(1)-deficient mice failed to penetrate the
      epidermis and became zigzagged owing to occlusion of the hair canal. Two major
      downstream signals of PLC, calcium elevation and protein kinase C activation,
      were impaired in the keratinocytes and skin of PLCdelta(1)-deficient mice. In
      addition, many cysts that had remarkable similarities to interfollicular
      epidermis, as well as hyperplasia of sebaceous glands, were observed.
      Furthermore, PLCdelta(1)-deficient mice developed spontaneous skin tumors that
      had characteristics of both interfollicular epidermis and sebaceous glands. From
      these results, we conclude that PLCdelta(1) is required for skin stem cell
      lineage commitment.

PMID- 12805214
TI  - Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and
      differentiation.
AB  - Contact of developing sensory organs with the external environment is established
      via the formation of openings in the skin. During eye development, eyelids first
      grow, fuse and finally reopen, thus providing access for visual information to
      the retina. Here, we show that eyelid opening is strongly inhibited in transgenic
      mice overexpressing the bone morphogenetic protein (BMP) antagonist noggin from
      the keratin 5 (K5) promoter in the epidermis. In wild-type mice, enhanced
      expression of the kinase-inactive form of BMPR-IB mediated by an adenovirus
      vector also inhibits eyelid opening. Noggin overexpression leads to reduction of
      apoptosis and retardation of cell differentiation in the eyelid epithelium, which
      is associated with downregulation of expression of the apoptotic receptors (Fas,
      p55 kDa TNFR), Id3 protein and keratinocyte differentiation markers (loricrin,
      involucrin). BMP-4, but not EGF or TGF-alpha, accelerates opening of the eyelid
      explants isolated from K5-Noggin transgenic mice when cultured ex vivo. These
      data suggest that the BMP signaling pathway plays an important role in regulation
      of genetic programs of eyelid opening and skin remodeling during the final steps
      of eye morphogenesis.

PMID- 12805215
TI  - GAP43 stimulates inositol trisphosphate-mediated calcium release in response to
      hypotonicity.
AB  - The identification of osmo/mechanosensory proteins in mammalian sensory neurons
      is still elusive. We have used an expression cloning approach to screen a human
      dorsal root ganglion cDNA library to look for proteins that respond to
      hypotonicity by raising the intracellular Ca(2+) concentration ([Ca(2+)](i)). We
      report the unexpected identification of GAP43 (also known as neuromodulin or
      B50), a membrane-anchored neuronal protein implicated in axonal growth and
      synaptic plasticity, as an osmosensory protein that augments [Ca(2+)](i) in
      response to hypotonicity. Palmitoylation of GAP43 plays an important role in the
      protein osmosensitivity. Depletion of intracellular stores or inhibition of
      phospholipase C (PLC) activity abrogates hypotonicity-evoked, GAP43-mediated
      [Ca(2+)](i) elevations. Notably, hypotonicity promoted the selective association
      of GAP43 with the PLC-delta(1) isoform, and a concomitant increase in inositol
      1,4,5-trisphosphate (IP(3)) formation. Collectively, these findings indicate that
      hypo-osmotic activation of GAP43 induces Ca(2+) release from IP(3)-sensitive
      intracellular stores. The osmosensitivity of GAP43 furnishes a mechanistic
      framework that links axon elongation with phospho inositide metabolism,
      spontaneous triggering of cytosolic Ca(2+) transients and the regulation of actin
      dynamics and motility at the growth cone in response to temporal and local
      mechanical forces.

PMID- 12805216
TI  - The B cell-specific major raft protein, Raftlin, is necessary for the integrity
      of lipid raft and BCR signal transduction.
AB  - Recent evidence indicates that membrane microdomains, termed lipid rafts, have a
      role in B-cell activation as platforms for B-cell antigen receptor (BCR) signal
      initiation. To gain an insight into the possible functioning of lipid rafts in B
      cells, we applied liquid chromatography electrospray ionization tandem mass
      spectrometry (LC-ESI-MS/MS) methodologies to the identification of proteins that
      co-purified with lipid rafts of Raji cells. Among these raft proteins, we
      characterized a novel protein termed Raftlin (raft-linking protein). Like the Src
      family kinase, Raftlin is localized exclusively in lipid rafts by fatty acylation
      of N-terminal Gly2 and Cys3, and is co-localized with BCR before and after BCR
      stimulation. Disruption of the Raftlin gene in the DT40 B-cell line resulted in a
      marked reduction in the quantity of lipid raft components, including Lyn and
      ganglioside GM1, while overexpression of Raftlin increased the content of raft
      protein. Moreover, BCR-mediated tyrosine phosphorylation and calcium mobilization
      were impaired by the lack of Raftlin and actually potentiated by overexpression
      of Raftlin. These data suggest that Raftlin plays a pivotal role in the formation
      and/or maintenance of lipid rafts, therefore regulating BCR-mediated signaling.

PMID- 12805217
TI  - LMP1, a viral relative of the TNF receptor family, signals principally from
      intracellular compartments.
AB  - Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded, ligand
      independent receptor that mimics CD40. We report here that LMP1 signals
      principally from intracellular compartments. LMP1 associates simultaneously with
      lipid rafts and with its signaling molecules, tumor necrosis factor-receptor (TNF
      R)-associated factors (TRAFs) and TNF-R1-associated death domain protein (TRADD)
      intracellularly, although it can be detected at low levels at the plasma
      membrane, indicating that most of LMP1's signaling complex resides in
      intracellular compartments. LMP1's signaling is independent of its accumulation
      at the plasma membrane in different cells, and as demonstrated by a mutant of
      LMP1 which has significantly reduced localization at the plasma membrane yet
      signals as efficiently as does wild-type LMP1. The fusion of the transmembrane
      domain of LMP1 to signaling domains of CD40, TNF-R1 and Fas activates their
      signaling; we demonstrate that a fusion of LMP1 with CD40 recruits TRAF2
      intracellularly. Our results imply that members of the TNF-R family can signal
      from intracellular compartments containing lipid rafts and may do so when they
      act in autocrine loops.

PMID- 12805218
TI  - Ras-GRF1 signaling is required for normal beta-cell development and glucose
      homeostasis.
AB  - Development of diabetes generally reflects an inadequate mass of insulin
      producing beta-cells. beta-cell proliferation and differentiation are regulated
      by a variety of growth factors and hormones, including insulin-like growth factor
      I (IGF-I). GRF1 is a Ras-guanine nucleotide exchange factor known previously for
      its restricted expression in brain and its role in learning and memory. Here we
      demonstrate that GRF1 is also expressed in pancreatic islets. Interestingly, our
      GRF1-deficient mice exhibit reduced body weight, hypoinsulinemia and glucose
      intolerance owing to a reduction of beta-cells. Whereas insulin resistance is not
      detected in peripheral tissues, GRF1 knockout mice are leaner due to increased
      lipid catabolism. The reduction in circulating insulin does not reflect defective
      glucose sensing or insulin production but results from impaired beta-cell
      proliferation and reduced neogenesis. IGF-I treatment of isolated islets from
      GRF1 knockouts fails to activate critical downstream signals such as Akt and Erk.
      The observed phenotype is similar to manifestations of preclinical type 2
      diabetes. Thus, our observations demonstrate a novel and specific role for Ras
      GRF1 pathways in the development and maintenance of normal beta-cell number and
      function.

PMID- 12805219
TI  - A role for VASP in RhoA-Diaphanous signalling to actin dynamics and SRF activity.
AB  - Vasodilator-stimulated phosphoprotein (VASP) is involved in multiple actin
      mediated processes, including regulation of serum response factor (SRF) activity.
      We used the SRF transcriptional assay to define functional domains in VASP and to
      show that they coincide with those required for F-actin accumulation, as
      determined by a quantitative FACS assay. We identified inactive VASP mutants that
      can interfere both with F-actin assembly and with SRF activation by wild-type
      VASP. These VASP mutants also inhibit actin-based motility of Vaccinia virus and
      Shigella flexneri. VASP-induced F-actin accumulation and SRF activation require
      both functional Rho and its effector mDia, and conversely, mDia-mediated SRF
      activation is critically dependent on functional VASP. VASP and mDia also
      associate physically in vivo. These findings show that VASP and mDia function
      cooperatively downstream of Rho to control F-actin assembly and SRF activity.

PMID- 12805220
TI  - Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase
      STRAD.
AB  - The LKB1 gene encodes a serine/threonine kinase mutated in Peutz-Jeghers cancer
      syndrome. Despite several proposed models for LKB1 function in development and in
      tumour suppression, the detailed molecular action of LKB1 remains undefined.
      Here, we report the identification and characterization of an LKB1-specific
      adaptor protein and substrate, STRAD (STe20 Related ADaptor). STRAD consists of a
      STE20- like kinase domain, but lacks several residues that are indispensable for
      intrinsic catalytic activity. Endogenous LKB1 and STRAD form a complex in which
      STRAD activates LKB1, resulting in phosphorylation of both partners. STRAD
      determines the subcellular localization of wild-type, but not mutant LKB1,
      translocating it from nucleus to cytoplasm. One LKB1 mutation previously
      identified in a Peutz-Jeghers family that does not compromise its kinase activity
      is shown here to interfere with LKB1 binding to STRAD, and hence with STRAD
      dependent regulation. Removal of endogenous STRAD by siRNA abrogates the LKB1
      induced G(1) arrest. Our results imply that STRAD plays a key role in regulating
      the tumour suppressor activities of LKB1.

PMID- 12805221
TI  - Schizosaccharomyces pombe AGC family kinase Gad8p forms a conserved signaling
      module with TOR and PDK1-like kinases.
AB  - The TOR protein is a phosphoinositide kinase-related kinase widely conserved
      among eukaryotes. Fission yeast tor1 encodes an ortholog of TOR, which is
      required for sexual development and growth under stressed conditions. We isolated
      gad8, which encodes a Ser/Thr kinase of the AGC family, as a high-copy suppressor
      of the sterility of a tor1 mutant. Disruption of gad8 caused phenotypes similar
      to those of tor1 disruption. Gad8p was less phosphorylated and its kinase
      activity was undetectable in tor1Delta cells. Three amino acid residues
      corresponding to conserved phosphorylation sites in the AGC family kinases,
      namely Thr387 in the activation loop, Ser527 in the turn motif and Ser546 in the
      hydrophobic motif, were important for the kinase activity of Gad8p. Tor1p was
      responsible for the phosphorylation of Ser527 and Ser546, whereas Ksg1p, a PDK1
      like kinase, appeared to phosphorylate Thr387 directly. Altogether, Tor1p, Ksg1p
      and Gad8p appear to constitute a signaling module for sexual development and
      growth under stressed conditions in fission yeast, which resembles the mTOR-PDK1
      S6K1 system in mammals and may represent a basic signaling module ubiquitous in
      eukaryotes.

PMID- 12805222
TI  - Regulation of the Wnt signaling pathway by disabled-2 (Dab2).
AB  - The adaptor molecule Disabled-2 (Dab2) has been shown to link cell surface
      receptors to downstream signaling pathways. Using a small-pool cDNA screening
      strategy, we identify that the N-terminal domain of Dab2 interacts with
      Dishevelled-3 (Dvl-3), a signaling mediator of the Wnt pathway. Ectopic
      expression of Dab2 in NIH-3T3 mouse fibroblasts attenuates canonical Wnt/beta
      catenin-mediated signaling, including accumulation of beta-catenin, activation of
      beta-catenin/T-cell-specific factor/lymphoid enhancer-binding factor 1-dependent
      reporter constructs, and endogenous cyclin D1 induction. Wnt stimulation leads to
      a time-dependent dissociation of endogenous Dab2-Dvl-3 and Dvl-3-axin
      interactions in NIH-3T3 cells, while Dab2 overexpression leads to maintenance of
      Dab2-Dvl-3 association and subsequent loss of Dvl-3-axin interactions. In
      addition, we find that Dab2 can associate with axin in vitro and stabilize axin
      expression in vivo. Mouse embryo fibroblasts which lack Dab2 exhibit constitutive
      Wnt signaling as evidenced by increased levels of nuclear beta-catenin and cyclin
      D1 protein levels. Based on these results, we propose that Dab2 functions as a
      negative regulator of canonical Wnt signaling by stabilizing the beta-catenin
      degradation complex, which may contribute to its proposed role as a tumor
      suppressor.

PMID- 12805223
TI  - Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice
      causes Purkinje cell death and ataxia.
AB  - PrP knockout mice with disruption of only the PrP-encoding region (Zurich I-type)
      remain healthy, whereas mice with deletions extending upstream of the PrP
      encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated
      with ectopic expression of Doppel in brain, particularly in Purkinje cells. The
      phenotype is abrogated by co-expression of full-length PrP. Doppel is 25% similar
      to PrP, has the same globular fold, but lacks the flexible N-terminal tail. We
      now show that in Zurich I-type PrP-null mice, expression of N-terminally
      truncated PrP targeted to Purkinje cells also leads to Purkinje cell loss and
      ataxia, which are reversed by PrP. Doppel and truncated PrP probably cause
      Purkinje cell degeneration by the same mechanism.

PMID- 12805224
TI  - The thyroid hormone receptor antagonizes CREB-mediated transcription.
AB  - Combinatorial regulation of transcription involves binding of transcription
      factors to DNA as well as protein-protein interactions between them. In this
      paper, we demonstrate the existence of a mutual transcriptional antagonism
      between the thyroid hormone receptor (TR) and the cyclic AMP response element
      binding protein (CREB), which involves a direct association of both transcription
      factors. TR inhibits transcriptional activity of CREB and represses activation of
      cAMP response element (CRE)-containing promoters. TR does not bind to the CRE in
      vitro, but in vivo the liganded receptor is tethered to the promoter through
      protein-protein interactions. In turn, expression of CREB reduces TR-dependent
      transcriptional responses. The association of TR with CREB inhibits the ability
      of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in
      the ligand-dependent recruitment of the p160 coactivators by TR. These results
      indicate the existence of a transcriptional cross-talk between CREB and TR
      signalling pathways, which can have important functional consequences.

PMID- 12805225
TI  - A novel boundary element may facilitate independent gene regulation in the
      Antennapedia complex of Drosophila.
AB  - The intrinsic enhancer-promoter specificity and chromatin boundary/insulator
      function are two general mechanisms that govern enhancer trafficking in complex
      genetic loci. They have been shown to contribute to gene regulation in the
      homeotic gene complexes from fly to mouse. The regulatory region of the Scr gene
      in the Drosophila Antennapedia complex is interrupted by the neighboring ftz
      transcription unit, yet both genes are specifically activated by their respective
      enhancers from such juxtaposed positions. We identified a novel insulator, SF1,
      in the Scr-ftz intergenic region that restricts promoter selection by the ftz
      distal enhancer in transgenic embryos. The enhancer-blocking activity of the full
      length SF1, observed in both embryo and adult, is orientation- and enhancer
      independent. The core region of the insulator, which contains a cluster of GAGA
      sites essential for its activity, is highly conserved among other Drosophila
      species. SF1 may be a member of a conserved family of chromatin
      boundaries/insulators in the HOM/Hox complexes and may facilitate the independent
      regulation of the neighboring Scr and ftz genes, by insulating the evolutionarily
      mobile ftz transcription unit.

PMID- 12805226
TI  - CtBP/BARS: a dual-function protein involved in transcription co-repression and
      Golgi membrane fission.
AB  - C-terminal-binding protein/brefeldin A-ADP ribosylated substrate (CtBP/BARS)
      plays key roles in development and oncogenesis as a transcription co-repressor,
      and in intracellular traffic as a promoter of Golgi membrane fission. Co
      repressor activity is regulated by NAD(H) binding to CtBP/BARS, while membrane
      fission is associated with its acyl-CoA-dependent acyltransferase activity. Here,
      we report the crystal structures of rat CtBP/BARS in a binary complex with
      NAD(H), and in a ternary complex with a PIDLSKK peptide mimicking the consensus
      motif (PXDLS) recognized in CtBP/BARS cellular partners. The structural data show
      CtBP/BARS in a NAD(H)-bound dimeric form; the peptide binding maps the
      recognition site for DNA-binding proteins and histone deacetylases to an N
      terminal region of the protein. The crystal structure together with the site
      directed mutagenesis data and binding experiments suggest a rationale for the
      molecular mechanisms underlying the two fundamental co-existing, but diverse,
      activities supported by CtBP/BARS in the nucleus and in Golgi membranes.

PMID- 12805227
TI  - High-affinity DNA binding by a Mot1p-TBP complex: implications for TAF
      independent transcription.
AB  - Yeast Mot1p, an abundant conserved member of the Snf2p-ATPase family of proteins,
      both dissociates TBP from DNA in vitro using the energy of ATP and represses gene
      transcription in vivo, yet paradoxically, loss of Mot1p function also leads to
      decreased transcription of certain genes. We conducted experiments utilizing
      fluorescently labeled DNA, TBP, fluorescence anisotropy spectroscopy and native
      gel electrophoresis to study Mot1p action. We have made a number of observations,
      the most intriguing being that a stable Mot1p-TBP complex has the ability to bind
      TATA DNA with high affinity, albeit with dramatically altered specificity. We
      propose that this altered TBP-DNA recognition is integral to Mot1p's ability to
      regulate transcription, and further postulate that the Mot1p-TBP complex delivers
      TBP to TAF-independent mRNA encoding genes.

PMID- 12805228
TI  - Autoregulation of FCA pre-mRNA processing controls Arabidopsis flowering time.
AB  - The timing of the transition to flowering is critical for reproductive success in
      plants. Arabidopsis FCA encodes an RNA-binding protein that promotes flowering.
      FCA expression is regulated through alternative processing of its pre-mRNA. We
      demonstrate here that FCA negatively regulates its own expression by ultimately
      promoting cleavage and polyadenylation within intron 3. This causes the
      production of a truncated, inactive transcript at the expense of the full-length
      FCA mRNA, thus limiting the expression of active FCA protein. We show that this
      negative autoregulation is under developmental control and requires the FCA WW
      protein interaction domain. Removal of introns from FCA bypasses the
      autoregulation, and the resulting increased levels of FCA protein overcomes the
      repression of flowering normally conferred through the up-regulation of FLC by
      active FRI alleles. The negative autoregulation of FCA may therefore have evolved
      to limit FCA activity and hence control flowering time.

PMID- 12805229
TI  - NSD1 is essential for early post-implantation development and has a catalytically
      active SET domain.
AB  - The nuclear receptor-binding SET domain-containing protein (NSD1) belongs to an
      emerging family of proteins, which have all been implicated in human malignancy.
      To gain insight into the biological functions of NSD1, we have generated NSD1
      deficient mice by gene disruption. Homozygous mutant NSD1 embryos, which initiate
      mesoderm formation, display a high incidence of apoptosis and fail to complete
      gastrulation, indicating that NSD1 is a developmental regulatory protein that
      exerts function(s) essential for early post-implantation development. We have
      also examined the enzymatic potential of NSD1 and found that its SET domain
      possesses intrinsic histone methyltransferase activity with specificity for Lys36
      of histone H3 (H3-K36) and Lys20 of histone H4 (H4-K20).

PMID- 12805230
TI  - HP1 binding to native chromatin in vitro is determined by the hinge region and
      not by the chromodomain.
AB  - We have isolated the complete coding sequences for two Xenopus laevis isoforms of
      heterochromatin protein 1, corresponding to HP1alpha and HP1gamma. The sequence
      of xHP1alpha shows considerable divergence from its mammalian homologues, whereas
      xHP1gamma is highly conserved. Functionally, xHP1alpha behaves identically to
      human HP1alpha. We observe unexpected differences between the two HP1 variants in
      binding native soluble chromatin, which seem to correlate with their distinct
      nuclear distributions in vivo. A surprising finding is that the characteristic
      interaction of HP1 chromodomains with histone H3 at methylated lysine 9 is not
      detected in preformed chromatin due to its inaccessibility. Instead, we localize
      a strong chromatin-binding activity to the short hinge region between the
      chromodomain and the chromoshadow domain of xHP1alpha but not xHP1gamma. This
      novel chromatin-binding activity has a non-specific DNA-binding component in
      addition to a linker histone-dependent preference for an altered chromatin
      structure with a likely heterochromatin organization.

PMID- 12805231
TI  - The nuclear actin-related proteins Arp7 and Arp9: a dimeric module that
      cooperates with architectural proteins for chromatin remodeling.
AB  - Nuclear actin-related proteins (ARPs) are essential components of chromatin
      remodeling and modifying complexes, but their functions and relationship to actin
      remain elusive. The yeast SWI/SNF and RSC complexes contain Arp7 and Arp9, and
      are shown to form a stable heterodimer with the properties of a functional
      module. Arp7 and Arp9 rely on their actin-related regions for heterodimerization,
      and their unique C-termini cooperate for assembly into RSC. We suggest that
      regulated ARP-ARP (and possibly ARP-beta-actin) heterodimerization might be a
      conserved feature of chromatin complexes. A RSC complex lacking Arp7/9 was
      isolated that displays robust nucleosome remodeling activity, suggesting a
      separate essential role for ARPs in the regulation of chromatin structure. A
      screen for suppressors of arp mutations yielded the DNA bending architectural
      transcription factor Nhp6, which interacts with RSC complex physically and
      functionally and shows facilitated binding to nucleosomes by RSC. We propose that
      Arp7/9 dimers function with DNA bending proteins to facilitate proper chromatin
      architecture and complex- complex interactions.

PMID- 12805233
TI  - Phenotyping hypertrophy: eschew obfuscation.

PMID- 12805232
TI  - Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome
      stability in vertebrates.
AB  - Translesion DNA synthesis (TLS) and homologous DNA recombination (HR) are two
      major postreplicational repair (PRR) pathways. The REV3 gene of Saccharomyces
      cerevisiae encodes the catalytic subunit of DNA polymerase zeta, which is
      involved in mutagenic TLS. To investigate the role of REV3 in vertebrates, we
      disruped the gene in chicken DT40 cells. REV3(-/-) cells are sensitive to various
      DNA-damaging agents, including UV, methyl methanesulphonate (MMS), cisplatin and
      ionizing radiation (IR), consistent with its role in TLS. Interestingly, REV3(-/
      ) cells showed reduced gene targeting efficiencies and significant increase in
      the level of chromosomal breaks in the subsequent M phase after IR in the G(2)
      phase, suggesting the involvement of Rev3 in HR-mediated double-strand break
      repair. REV3(-/-) cells showed significant increase in sister chromatid exchange
      events and chromosomal breaks even in the absence of exogenous genotoxic stress.
      Furthermore, double mutants of REV3 and RAD54, genes involved in HR, are
      synthetic lethal. In conclusion, Rev3 plays critical roles in PRR, which accounts
      for survival on naturally occurring endogenous as well as induced damages during
      replication.

PMID- 12805234
TI  - Cell-to-cell coupling between host and donor cells in the in situ myocardium.

PMID- 12805235
TI  - Apolipoprotein A-II: active or passive role in familial combined hyperlipidemia.

PMID- 12805236
TI  - T-tubule function in mammalian cardiac myocytes.
AB  - The transverse tubules (t-tubules) of mammalian cardiac ventricular myocytes are
      invaginations of the surface membrane. Recent studies have suggested that the
      structure and function of the t-tubules are more complex than previously
      believed; in particular, many of the proteins involved in cellular Ca2+ cycling
      appear to be concentrated at the t-tubule. Thus, the t-tubules are an important
      determinant of cardiac cell function, especially as the main site of excitation
      contraction coupling, ensuring spatially and temporally synchronous Ca2+ release
      throughout the cell. Changes in t-tubule structure and protein expression occur
      during development and in heart failure, so that changes in the t-tubules may
      contribute to the functional changes observed in these conditions. The purpose of
      this review is to provide an overview of recent studies of t-tubule structure and
      function in cardiac myocytes.

PMID- 12805237
TI  - Role of sodium-calcium exchanger in modulating the action potential of
      ventricular myocytes from normal and failing hearts.
AB  - Increased Na+-Ca2+ exchange (NCX) activity in heart failure and hypertrophy may
      compensate for depressed sarcoplasmic reticular Ca2+ uptake, provide inotropic
      support through reverse-mode Ca2+ entry, and/or deplete intracellular Ca2+
      stores. NCX is electrogenic and depends on Na+ and Ca2+ transmembrane gradients,
      making it difficult to predict its effect on the action potential (AP). Here, we
      examine the effect of [Na+]i on the AP in myocytes from normal and pacing-induced
      failing canine hearts and estimate the direction of the NCX driving force using
      simultaneously recorded APs and Ca2+ transients. AP duration shortened with
      increasing [Na+]i and was correlated with a shift in the reversal point of the
      NCX driving force. At [Na+]i > or =10 mmol/L, outward NCX current during the
      plateau facilitated repolarization, whereas at 5 mmol/L [Na+]i, NCX had a
      depolarizing effect, confirmed by partially inhibiting NCX with exchange
      inhibitory peptide. Exchange inhibitory peptide shortened the AP duration at 5
      mmol/L [Na+]i and prolonged it at [Na+]i > or =10 mmol/L. With K+ currents
      blocked, total membrane current was outward during the late plateau of an AP
      clamp at 10 mmol/L [Na+]i and became inward close to the predicted reversal point
      for the NCX driving force. The results were reproduced using a computer model.
      These results indicate that NCX plays an important role in shaping the AP of the
      canine myocyte, helping it to repolarize at high [Na+]i, especially in the
      failing heart, but contributing a depolarizing, potentially arrhythmogenic,
      influence at low [Na+]i.

PMID- 12805238
TI  - Shear stress-mediated chromatin remodeling provides molecular basis for flow
      dependent regulation of gene expression.
AB  - Shear stress (SS), the tangential component of hemodynamic forces, modulates the
      expression of several genes in endothelial cells. However, no information is
      available about its effect on chromatin structure, which plays a key role in gene
      transcription. In this study, a link between SS and chromatin remodeling was
      established in human umbilical vein endothelial cells (HUVECs). HUVECs were
      exposed to SS of 10 dyne/cm2 per second, in the presence or absence of the
      histone deacetylase inhibitor trichostatin A, and assayed for histone H3 and
      histone H4 modifications. SS induced histone H3 serine phosphorylation at
      position 10 (S10) and lysine acetylation at position 14 (K14) but required
      trichostatin A to induce H3 phosphoacetylation and H4 acetylation. The
      phosphatidylinositol 3-kinase inhibitor wortmannin and the mitogen-activated
      protein kinase inhibitor PD98059 decreased SS-dependent histone H3
      phosphorylation, without affecting its acetylation; the p38 inhibitor SB203580
      reduced both H3 phosphorylation and acetylation, whereas the protein kinase A
      inhibitor PKI-tide reduced histone H3 acetylation. Remarkably, the abrogation of
      histone acetylation inhibited SS-dependent c-fos expression. SS also activated
      ribosomal S6 kinase-2 and mitogen- and stress-activated kinase-1 protein kinases
      and promoted the formation of a cAMP-responsive element-binding protein
      (CREB)/CREB-binding protein complex, providing the molecular basis for the
      increase in histone acetyltransferase activity observed in HUVECs exposed to SS.
      Finally, the effect of SS on chromatin remodeling was examined. In HUVECs exposed
      to SS, chromatin within c-fos and c-jun promoters was specifically
      immunoprecipitated by an antibody against acetylated histone H3 on K14. These
      results indicate that SS induces posttransduction modifications of histones; this
      is an early step toward the flow-dependent regulation of gene expression.

PMID- 12805239
TI  - Roles of the two active sites of somatic angiotensin-converting enzyme in the
      cleavage of angiotensin I and bradykinin: insights from selective inhibitors.
AB  - Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each
      bearing a functional active site. The in vivo contribution of each active site to
      the release of angiotensin II (Ang II) and the inactivation of bradykinin (BK) is
      still unknown. To gain insights into the functional roles of these two active
      sites, the in vitro and in vivo effects of compounds able to selectively inhibit
      only one active site of ACE were determined, using radiolabeled Ang I or BK, as
      physiological substrates of ACE. In vitro studies indicated that a full
      inhibition of the Ang I and BK cleavage requires a blockade of the two ACE active
      sites. In contrast, in vivo experiments in mice demonstrated that the selective
      inhibition of either the N-domain or the C-domain of ACE by these inhibitors
      prevents the conversion of Ang I to Ang II, while BK protection requires the
      inhibition of the two ACE active sites. Thus, in vivo, the cleavage of Ang I and
      BK by ACE appears to obey to different mechanisms. Remarkably, in vivo the
      conversion of Ang I seems to involve the two active sites of ACE, free of
      inhibitor. Based on these findings, it might be suggested that the gene
      duplication of ACE in vertebrates may represent a means for regulating the
      cleavage of Ang I differently from that of BK.

PMID- 12805240
TI  - Vascular endothelial growth factor-B promotes in vivo angiogenesis.
AB  - Vascular endothelial growth factors (VEGFs) and their receptors have emerged as
      central regulators of the angiogenic process. However, involvement of VEGF-B, one
      of these factors, in angiogenesis remains obscure. Mice received subcutaneous
      injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF
      B167 or with rhVEGF-A165. After 14 days, cell ingrowth in the Matrigel plug was
      increased by 2.0- and 2.5-fold in rhVEGF-B167-treated and rhVEGF-A165-treated
      mice, respectively (P<0.01), in association with a raise in phospho-Akt/Akt (1.8
      fold, P<0.01) and endothelial NO synthase (eNOS) (1.80- and 1.60-fold,
      respectively; P<0.05) protein levels measured by Western blot. VEGF-B-induced
      cell ingrowth was impaired by treatment with NOS inhibitor (NG-nitro-l-arginine
      methyl ester; L-NAME, 10 mg/kg per day). Treatment with neutralizing antibody
      directed against the VEGF-B receptor VEGF-R1 (anti-VEGFR1, 10 microg) completely
      abrogated VEGF-B-related effects. Proangiogenic effect of VEGF-B was confirmed in
      a mouse model of surgically induced hindlimb ischemia. Plasmids containing human
      form of VEGF-A (phVEGF-A165) or VEGF-B (phVEGF-B167 or phVEGF-B186) were
      administered by in vivo electrotransfer. Angiographic score at day 28 showed
      significant improvement in ischemic/nonischemic leg ratio by 1.4- and 1.5-fold in
      mice treated with phVEGF-B167 and phVEGF-B186, respectively (P<0.05). Laser
      Doppler perfusion data also evidenced a 1.5-fold increase in phVEGF-B167-treated
      and phVEGF-B186-treated mice (P<0.05). Such an effect was associated with an
      upregulation of phospho-Akt/Akt and eNOS protein levels in the ischemic legs and
      was hampered by treatment with anti-VEGFR1. This study demonstrates for the first
      time that VEGF-B, in part through its receptor VEGF-R1, promotes angiogenesis in
      association with an activation of Akt and eNOS-related pathways.

PMID- 12805241
TI  - Focal adhesion kinase is activated and mediates the early hypertrophic response
      to stretch in cardiac myocytes.
AB  - Previously we reported that the rapid activation of the Fak/Src multicomponent
      signaling complex mediates load-induced activation of growth and survival
      signaling pathways in adult rat heart. In this study, we report that 5% to 20%
      (10-minute) cyclic stretch (1 Hz) of neonatal rat ventricular myocytes (NRVMs)
      was paralleled by increases of Fak phosphorylation at Tyr-397 (from 1.5- to 2.8
      fold), as detected by anti-Fak-pY397 phosphospecific antibody. Moreover, 15%
      cyclic stretch lasting from 10 to 120 minutes increased Fak phosphorylation at
      Tyr-397 by 2.5- to 3.5-fold. This activation was accompanied by a dramatic change
      in Fak localization in NRVMs from densely concentrated in the perinuclear regions
      in nonstretched cells to aggregates regularly distributed along the myofilaments
      in stretched cells. Furthermore, a 4-hour cyclic stretch enhanced the activity of
      an atrial natriuretic factor (ANF) promoter-luciferase reporter gene by 2.7-fold.
      Disrupting endogenous Fak/Src signaling either by expression of a dominant
      negative Fak mutant with phenylalanine substituted for Tyr-397 or by treatment
      with a c-Src pharmacological inhibitor (PP-2) markedly attenuated stretch-induced
      Fak activation and clustering at myofilaments and inhibited stretch-induced ANF
      gene activation. On the other hand, overexpression of wild-type Fak potentiated
      the stretch-induced Fak phosphorylation but did not enhance either baseline or
      stretch-induced ANF promoter-luciferase reporter gene activity compared with the
      responses of nontransfected NRVMs. These findings identify Fak as an important
      element in the early responses induced by stretch in cardiac myocytes, indicating
      that it may coordinate the cellular signaling machinery that controls gene
      expression program associated with load-induced cardiac myocyte hypertrophy.

PMID- 12805242
TI  - Effects of adenovirus-mediated sorcin overexpression on excitation-contraction
      coupling in isolated rabbit cardiomyocytes.
AB  - To evaluate the effect of sorcin on cardiac excitation-contraction coupling,
      adult rabbit ventricular myocytes were transfected with a recombinant adenovirus
      coding for human sorcin (Ad-sorcin). A beta-galactosidase adenovirus (Ad-LacZ)
      was used as a control. Fractional shortening in response to 1-Hz field
      stimulation (at 37 degrees C) was significantly reduced in Ad-sorcin-transfected
      myocytes compared with control myocytes (2.10+/-0.05% [n=311] versus 2.42+/-0.06%
      [n=312], respectively; P<0.001). Action potential duration (at 20 degrees C) was
      significantly less in the Ad-sorcin group (458+/-22 ms, n=11) compared with the
      control group (520+/-19 ms, n=10; P<0.05). In voltage-clamped, fura 2-loaded
      myocytes (20 degrees C), a reduced peak-systolic and end-diastolic [Ca2+]i was
      observed after Ad-sorcin transfection. L-type Ca2+ current amplitude and time
      course were unaffected. Caffeine-induced Ca2+ release from the sarcoplasmic
      reticulum (SR) and the accompanying inward Na+-Ca2+ exchanger (NCX) current
      revealed a significantly lower SR Ca2+ content and faster Ca2+-extrusion kinetics
      in Ad-sorcin-transfected cells. Higher NCX activity after Ad-sorcin transfection
      was confirmed by measuring the NCX current-voltage relationship. beta-Escin
      permeabilized rabbit cardiomyocytes were used to study the effects of sorcin
      overexpression on Ca2+ sparks imaged with fluo 3 at 145 to 160 nmol/L [Ca2+]
      using a confocal microscope. Under these conditions, caffeine-mediated SR Ca2+
      release was not different between the two groups. Spontaneous spark frequency,
      duration, width, and amplitude were lower in sorcin-overexpressing myocytes. In
      summary, sorcin overexpression in rabbit cardiomyocytes decreased Ca2+-transient
      amplitude predominantly by lowering SR Ca2+ content via increased NCX activity.
      The effect of sorcin overexpression on Ca2+ sparks indicates an effect on the
      ryanodine receptor that may also influence excitation-contraction coupling.

PMID- 12805243
TI  - Altered expression of small-conductance Ca2+-activated K+ (SK3) channels
      modulates arterial tone and blood pressure.
AB  - The endothelium is a critical regulator of vascular tone, and dysfunction of the
      endothelium contributes to numerous cardiovascular pathologies. Recent studies
      suggest that apamin-sensitive, small-conductance, Ca2+-activated K+ channels may
      play an important role in active endothelium-dependent vasodilations, and
      expression of these channels may be altered in disease states characterized by
      vascular dysfunction. Here, we used a transgenic mouse (SK3T/T) in which SK3
      expression levels can be manipulated with dietary doxycycline (DOX) to test the
      hypothesis that the level of expression of the SK subunit, SK3, in endothelial
      cells alters arterial function and blood pressure. SK3 protein was elevated in
      small mesenteric arteries from SK3T/T mice compared with wild-type mice and was
      greatly suppressed by dietary DOX. SK3 was detected in the endothelium and not in
      the smooth muscle by immunohistochemistry. In whole-cell patch-clamp experiments,
      SK currents in endothelial cells from SK3T/T mice were almost completely
      suppressed by dietary DOX. In intact arteries, SK3 channels contributed to
      sustained hyperpolarization of the endothelial membrane potential, which was
      communicated to the arterial smooth muscle. Pressure- and phenylephrine-induced
      constrictions of SK3T/T arteries were substantially enhanced by treatment with
      apamin, suppression of SK3 expression with DOX, or removal of the endothelium. In
      addition, suppression of SK3 expression caused a pronounced and reversible
      elevation of blood pressure. These results indicate that endothelial SK3 channels
      exert a profound, tonic, hyperpolarizing influence in resistance arteries and
      suggest that the level of SK3 channel expression in endothelial cells is a
      fundamental determinant of vascular tone and blood pressure.

PMID- 12805244
TI  - Alcohol consumption patterns and HbA1c, C-peptide and insulin concentrations in
      men.
AB  - OBJECTIVE: Observational studies support inverse associations between moderate
      alcohol consumption and fasting insulin concentrations, but the importance of
      drinking pattern on the effect of alcohol on insulin sensitivity has not been
      fully explored. We examined the relations of alcohol consumption patterns
      including average daily consumption, frequency of consumption and drinking with
      meals-to fasting insulin, fasting c-peptide and hemoglobin A1c (HbA1c). METHODS:
      A cross-sectional study of 462 disease-free men selected from the Health
      Professionals' Follow-up Study to provide information on a range of drinking
      patterns. Study participants were 48 to 82 years of age who provided a blood
      sample and detailed information on diet, life-style and alcohol consumption
      patterns in 1994. Among the study participants, 267 men provided a fasting blood
      sample and contributed to the analyses of insulin and c-peptide. RESULTS:
      Biologic markers were not strongly related to average alcohol consumption.
      Compared to abstainers, differences in insulin concentrations-all statistically
      non-significant-were 0.06, 1.25, 1.02, and 0.12 micro U/mL for consumers of <1, 1
      1.9, 2-2.9, 3+ drinks per day, respectively. The frequency of alcohol consumption
      was inversely related to fasting c-peptide and insulin concentrations after
      controlling for average alcohol consumption and other potential confounding
      variables. Compared to men who reported consuming alcohol one to three days per
      week, c-peptide concentrations were 0.08 ng/mL and 0.29 ng/mL lower (p-trend =
      0.04) in men who reported consuming alcohol on four to five days per week and six
      to seven days per week, respectively. Men who consumed alcohol on most days also
      had lower fasting insulin levels than more irregular drinkers (p-trend = 0.05).
      CONCLUSIONS: Our results suggest that frequent alcohol consumption is inversely
      related to fasting c-peptide and insulin concentrations.

PMID- 12805245
TI  - Effects of plant-based diets high in raw or roasted almonds, or roasted almond
      butter on serum lipoproteins in humans.
AB  - OBJECTIVE: To compare the lipid-altering effect of roasted salted almonds and
      roasted almond butter with that of raw almonds, as part of a plant-based diet.
      METHODS: Thirty-eight free-living, hypercholesterolemic men (n = 12) and women (n
      = 26) with a mean total serum cholesterol (TC) of 245 + 29 mg/dL (mean + SD)
      followed a heart-healthy diet including 100g of one of three forms of almonds:
      roasted salted almonds, roasted almond butter or raw almonds for four weeks.
      Measurements of serum TC, triglycerides (TG), selected lipoproteins and blood
      pressure were taken at baseline and after four weeks. RESULTS: All three forms of
      almonds in the context of a heart-healthy diet significantly lowered low-density
      lipoprotein-cholesterol (LDL) from baseline to the completion of the study. Both
      raw and roasted almonds significantly lowered TC, whereas the decrease by almond
      butter (in a smaller cohort) did not reach statistical significance. High-density
      lipoprotein-cholesterol (HDL) did not significantly change with raw or roasted
      almonds but slightly increased with almond butter. At the end of the study, blood
      pressure did not change significantly from baseline values for any of the groups.
      CONCLUSION: These results suggest that unblanched almonds-whether raw, dry
      roasted, or in roasted butter form-can play an effective role in cholesterol
      lowering, plant-based diets.

PMID- 12805246
TI  - Bone density in axial and appendicular skeleton in patients with lactose
      intolerance: influence of calcium intake and vitamin D status.
AB  - BACKGROUND: Lactose intolerance (LI) is a common enzymatic insufficiency,
      manifesting by poor tolerance of dairy products, leading to low calcium intake
      and poor calcium absorption from dairy products. These changes might lead to an
      impairment of bone metabolism [1]. OBJECTIVES: To evaluate the impact of LI on
      quantitative bone parameters in axial and appendicular skeletal sites. To assess
      the impact of calcium intake from dairy and non-dairy nutritional sources,
      calcium regulating hormones and bone turnover on quantitative bone parameters in
      LI patients. METHODS: We evaluated calcium intake and bone status in sixty-six
      patients with LI, 49 women and 17 men, aged 20 to 78. Bone mass was assessed at
      the lumbar spine (LS), total hip (TH) and femoral neck (FN) by dual-energy x-ray
      absorptiometry (DEXA) and at the radius, tibia, phalanx by quantitative
      ultrasound. Serum calcium, albumin, inorganic phosphate, calcium regulating
      hormones and markers of bone turnover were evaluated. RESULTS: Total daily
      calcium intake was below the recommended by the American Dietetic Association [2]
      in all study participants (mean 692 mg/day +/- 162). Elevated level of urinary
      deoxypyridinoline crosslinks (DPD) was observed in 63 (96%) patients and was
      negatively correlated with total daily calcium intake (r = -0.998, p = 0.025) and
      with nondairy calcium intake (r = -0.34, p = 0.015). Parathyroid hormone (PTH)
      level in the upper third of normal range (45-65 ng/L) was observed in 11 (17%)
      patients. Parathyroid hormone (PTH) was inversely correlated with total calcium
      intake (r = -0.4, p = 0.001), dairy calcium intake (r = -0.83, p = 0.05), non
      dairy calcium intake (r = -0.29, p = 0.043), 25OHD(3) serum level (r = -0.3, p =
      0.007) and positively correlated with bone turnover markers (deoxypyridinoline
      crosslinks [DPD], r = 0.36, p = 0.01 and bone specific alkaline phosphatase
      [BSAP] r = 0.36, p = 0.01). Decrease in quantitative bone parameters compared to
      age-matched controls was observed in the axial and in the appendicular skeleton
      in men and in postmenopausal women: mean z-score for LS -0.87 +/- 0.22 and -1.32
      +/- 0.65, p = 0.004 and 0.015, tibia -1.15 +/- 0.53 and -0.44 +/- 0.044, p <
      0.001 and 0.27, phalanx -0.98 +/- 0.22 and -0.52 +/- 0.98, p < 0.001. We observed
      decrease in bone mass in patients with serum PTH in the upper tertile of normal
      range in the FN (z-score -0.57 +/- 0.6 versus -0.03 +/- 0.9, p = 0.025), TH (
      0.51 +/- 0.96 versus 0.04 +/- 0.9, p = 0.05) and radius (-1.84 +/- 0.27 versus 
      0.07 +/- 1.61, p = 0.025, respectively). z-scores in FN and TH positively
      correlated with serum 25OHD(3) level (r = 0.31, 0.29; p = 0.014, 0.019). In
      postmenopausal women serum 25OHD(3) level correlated also with LS z-scores (r =
      0.52, p = 0.004); FN and TH z-scores negatively correlated with DPD level (r = 
      0.51, p = 0.02 and r = -0.55, p = 0.04). CONCLUSION: LI state may lead to
      increased bone turnover and decreased bone mass especially in men and
      postmenopausal women. Impaired vitamin D status and low calcium intake may be
      deleterious to bone in this condition.

PMID- 12805247
TI  - Effect of five-year supplementation of vitamin C on serum vitamin C concentration
      and consumption of vegetables and fruits in middle-aged Japanese: a randomized
      controlled trial.
AB  - OBJECTIVE: This study was aimed at evaluating the effect of long-term vitamin C
      supplementation on serum and dietary vitamin C and identifying the factors
      associated with change in serum concentration. METHODS: A total of 439 subjects
      with atrophic gastritis initially participated in a randomized clinical trial
      using vitamin C and beta-carotene to prevent gastric cancer. We originally
      randomized the participants into four treatment groups using a 2x2 factorial
      design, whereby 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C were
      administered in a double-blind manner. The beta-carotene component was terminated
      early after a mean treatment duration of four months. Before and upon early
      termination of beta-carotene supplementation, 134 subjects dropped out this
      trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg
      or 500 mg daily for five years. RESULTS: Changes in serum vitamin C were
      significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0-49.9)
      than in the low-dose group (13.0% increase, 5.1-20.9) or in the dropout group
      (3.3% increase, -2.1-8.6) after five-year supplementation. The serum vitamin C at
      baseline was negatively associated with changes in serum vitamin C (p < 0.0001),
      while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female
      gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the
      supplementation group was almost identical before and after five-year
      supplementation of vitamin C (2.31 mg/day decrease, 95% CI = -15.3-10.7), while a
      17.7 mg/day decrease (95% CI = -44.2-8.86) was observed in the drop-out group.
      CONCLUSION: Five-year vitamin C supplementation induces a remarkable increase in
      serum vitamin C concentration, and our intervention program appears to have no
      effect on dietary vitamin C intake.

PMID- 12805248
TI  - Effects of phenol-depleted and phenol-rich diets on blood markers of oxidative
      stress, and urinary excretion of quercetin and kaempferol in healthy volunteers.
AB  - OBJECTIVE: Epidemiological studies have suggested beneficial effects of dietary
      polyphenols in reducing the risk of chronic diseases. This study was performed to
      investigate the effects of polyphenol-depleted and polyphenol-rich diets on blood
      oxidative stress markers and urinary excretions of major phenols. METHODS:
      Nineteen healthy female non-smokers 19 to 21 years of age took part in the study,
      which consisted of two dietary intervention periods separated by three days.
      Experimental diets were composed of common foods selected to comply with low
      contents of polyphenols for phenol-depleted intervention and high contents of
      polyphenols for phenol-rich diets. Blood and urine samples were collected on day
      0, 3 and 6 of each intervention. Duplicate portions of foods provided to the
      subjects were also collected. Blood oxidative stress markers included plasma
      antioxidant vitamins, erythrocyte superoxide dismutase (SOD) activity and
      lymphocyte DNA damage. Urinary excretions of major phenols were measured to
      affirm bioavailability of dietary phenols. RESULTS: Plasma alpha-tocopherol and
      beta-carotene concentrations were slightly decreased on day 3 and 6 of the phenol
      depleted dietary intervention period, although no change was observed with phenol
      rich diets. The erythrocyte SOD activity was also slightly decreased during
      phenol-depleted dietary intervention. However, at day 6 of the phenol-rich
      intervention, the activity of SOD was significantly increased by 41%. Tail moment
      and tail length of lymphocyte DNA as markers of DNA damage were higher on day 6
      of phenol-depleted intervention, although only tail moment showed a statistical
      significance. The average intakes of quercetin and kaempferol during the phenol
      rich intervention were 21 mg/day and 9 mg/day, respectively. The average urinary
      excretion rates during phenol-rich intervention were 2.06% for quercetin and
      0.46% for kaempferol. There were positive correlations between erythrocyte SOD
      activity and urinary concentration of quercetin or kaempferol. CONCLUSIONS: These
      results suggest that polyphenol-rich diets may decrease the risk of chronic
      diseases by reducing oxidative stress.

PMID- 12805249
TI  - B vitamins and plasma homocysteine concentrations in an urban and rural area of
      Costa Rica.
AB  - OBJECTIVE: We studied the association between total plasma homocysteine (tHcy)
      concentrations and folate, B(12), and B(6) status in the urban and rural areas of
      Costa Rica. SUBJECTS AND METHODS: We determined plasma tHcy concentrations and
      assessed dietary folate, B(12) and B(6) intake by a food frequency questionnaire
      in 462 subjects selected by stratified random sampling in the urban and rural
      areas of Puriscal, Costa Rica. Plasma folate and vitamin B(12) concentrations
      were measured in women. RESULTS: THcy concentrations were higher (p < 0.01) in
      the rural compared with the urban area: 12.0 micro mol/L vs. 8.9 micro mol/L in
      men, and women 7.3 micro mol/L vs. 5.5 micro mol/L in women, respectively. The
      prevalence of hyperhomocysteinemia (greater than 15.0 micro mol/L) was twice as
      high in rural compared with urban men (19.8% vs. 10.8%, p = 0.06) and women (6.6%
      vs. 3.4%, p = 0.26). Most study subjects (98%) had folate intakes that were less
      than the recommended 400 micro g/day. In women, 31% of those living in the urban
      area and 40% of those in the rural area had plasma folate concentrations of less
      than 6.8 nmol/L, an indicator of folate deficiency. In women, age-adjusted mean
      tHcy concentrations ( micro mol/L) were higher in the lowest compared with
      highest quintiles for dietary vitamin B(6) (9.9 vs. 5.4, p < 0.05), B(12) (9.2
      vs. 4.9, p < 0.01), and folate (7.0 vs. 5.7, p = 0.87). Similar results were
      found for plasma B(12) (9.9 vs. 5.4, p < 0.01) and folate (10.5 vs. 5.0, p <
      0.0001). CONCLUSIONS: Residents of the rural area in Puriscal, Costa Rica have
      higher plasma concentrations of tHcy and lower intake of B vitamins, particularly
      in women. Because these characteristics are associated with high risk of
      cardiovascular disease, the efficacy of food fortification program in rural areas
      should be carefully addressed.

PMID- 12805250
TI  - Biochemical antioxidant levels respond to supplementation with an enriched drink
      in frail elderly people.
AB  - OBJECTIVE: To investigate whether a drink enriched with essential vitamins and
      minerals can improve biochemical status of enzymatic and non-enzymatic
      antioxidants in frail elderly people. METHODS: A six-month randomized, double
      blind, placebo controlled intervention study. Frail elderly people 65 years of
      age or older, with a body mass index (BMI) below 25 kg/m(2) and residing in a
      home for the elderly or in sheltered housing. Enriched (with essential vitamins
      and minerals in 30% to 150% of RDA and higher levels of antioxidants) drink (n =
      28) or placebo (n = 27) to be taken twice a day in addition to the normal food
      consumed. Plasma levels of vitamin C, vitamin E, antioxidant capacity (TEAC),
      cysteine, uric acid and whole blood levels of total thiol and glutathione
      peroxidase (GSH-Px), dietary intake. RESULTS: Changes in vitamin E (16 +/- 2 vs.
      2 +/- 1 mmol/L), vitamin C (37 +/- 5 vs. 1 +/- 5 mmol/L), TEAC (38 +/- 15 vs. -10
      +/- 11 mmol/L Trolox eq) and cysteine (17 +/- 10 vs. 0.4 +/- 6 mmol/L) were
      significantly different between groups (p < 0.05). There was a trend towards
      significant changes in erythrocyte glutathione peroxidase (-0.2 +/- 3 vs. -10 +/-
      7 U/mg Hb, p = 0.097). Baseline dietary intake of antioxidant vitamins was below
      2/3 RDA for a substantial proportion (43% to 76%) of subjects. CONCLUSIONS:
      Supplementation with an enriched drink can raise plasma levels of enzymatic and
      non-enzymatic antioxidants in frail elderly people.

PMID- 12805251
TI  - Female rats are protected against oxidative stress during copper deficiency.
AB  - BACKGROUND: Copper deficiency induces a dramatic decrease of superoxide dismutase
      activity and leads to alteration of antioxidant defense systems. METHODS: and
      OBJECTIVE: Experiments were conducted in weanling male, intact and ovariectomized
      female rats, fed either a copper-adequate or copper-deficient diet for seven
      weeks, in order to determine whether endogenous estrogen could modulate oxidative
      stress and the severity of copper-deficiency. RESULTS: Feeding male rats a copper
      deficient diet induced typical signs of copper deficiency, such as decreased
      hepatic copper, growth retardation, anemia, heart hypertrophy, pancreas atrophy
      and hypercholesterolemia. Furthermore, copper deficiency increased the amount of
      lipid peroxidation products in the heart, liver and pancreas following in vitro
      iron induction. Although levels of hepatic copper in copper-deficient females
      were similar to those of their male counterparts, the females were partially
      protected from the adverse effects of the deficiency (no growth retardation, less
      severe anemia, lesser extent of lipid peroxidation). Thus, female rats are
      provided with a greater degree of protection against oxidative damage than males.
      However, females did not appear to be protected against pancreas atrophy, heart
      enlargement and hypercholesterolemia induced by copper deficiency. This observed
      partial protection of females was lost after ovariectomy as shown by decreased
      body weight and hematocrit, heart enlargement and higher tissue peroxidation in
      ovariectomized females compared to intact females. CONCLUSIONS: The results
      suggest that the partial protection of copper deficient females is related to the
      antioxidant properties of estrogens. The protective action of estrogen against
      oxidative stress is of particular importance when antioxidant defenses are
      decreased as shown in this experimental model.

PMID- 12805252
TI  - Postprandial leptin response to carbohydrate and fat meals in obese women.
AB  - OBJECTIVE: To assess the postprandial leptin responses to a carbohydrate and a
      fatty meal in obese subjects and its association with postprandial insulin
      response. METHODS: Eight obese and 11 lean women were given, in a random order,
      an isocaloric carbohydrate meal (3.43 MJ, 166g of carbohydrates, 38g of proteins)
      or fat meal (3.35 MJ, 70g of fat, 36g of proteins) or remained fasting. Blood
      samples were collected hourly during the nine hours after the meal for leptin,
      insulin, C-peptide and glucose determinations. RESULTS: In obese subjects, as in
      lean subjects, postprandial leptin response, calculated as the increment above
      fasting values, was higher after the carbohydrate meal than after the fatty meal
      (p < 0.01). However, after the carbohydrate meal, postprandial leptin increment
      was lower (p < 0.05) in obese subjects than in lean controls. In contrast, there
      was no difference in postprandial leptin response between lean and obese subjects
      after the fatty meal. Correlation analyses showed that the area under the
      postprandial leptin response curve (leptin AUC) was correlated to insulin AUC in
      lean (r = 0.70, p < 0.01), but not in obese subjects. CONCLUSION: These results
      indicate that postprandial leptin response is lower after a carbohydrate meal in
      obese women than in lean controls, suggesting an impairment of postprandial
      leptin regulation in obese women.

PMID- 12805253
TI  - Intra-hospital dissemination of quinupristin/dalfopristin- and vancomycin
      resistant Enterococcus faecium in a paediatric ward of a German hospital.
AB  - OBJECTIVES: To demonstrate nosocomial transmission of Enterococcus faecium
      resistant to quinupristin/dalfopristin and vancomycin/teicoplanin among
      paediatric patients in a German hospital ward. MATERIALS AND METHODS: Multiply
      resistant E. faecium were isolated from three female patients aged 9 months, 2
      and 15 years during a 10 day time span. Antibiotic susceptibilities were
      determined by microbroth dilution. Clonal relatedness among the isolates was
      investigated via SmaI-macrorestriction analysis by PFGE, multilocus sequence
      typing (MLST), and plasmid profiling. Presence of virulence and resistance
      determinants was tested by polymerase chain reaction (PCR). Selected resistance
      genes were localized by Southern hybridizations. RESULTS: A single E. faecium
      isolate per patient was investigated. All exhibited resistances to
      quinupristin/dalfopristin, vancomycin/teicoplanin, streptomycin (high-level),
      penicillin/ampicillin, erythromycin, oxytetracycline, chloramphenicol, rifampicin
      and fusidic acid. The isolates were susceptible to linezolid only and
      intermediately resistant to fluoroquinolones including moxifloxacin. PFGE
      revealed identical patterns for all three isolates. PCRs for virulence
      determinants hyaluronidase and enterococcal surface protein, esp, were negative,
      whereas PCR for the enterocin A gene was positive. MLST identified clonal type [8
      5-1-1-1-1-1] belonging to a clonal subgroup C1 of hospital- and outbreak-related
      E. faecium. Southern hybridizations located several resistance genes (erm(B),
      vat(D), vanA) on a large plasmid, which was transferable in mating experiments
      with an E. faecium recipient. CONCLUSIONS: These data show routes of
      dissemination of resistance to multiple antibiotics including streptogramins and
      glycopeptides in E. faecium via vertical and/or horizontal gene transfer. The
      isolates spread in the absence of a direct selective pressure, as none of the
      patients had received earlier streptogramin or glycopeptide therapy.

PMID- 12805255
TI  - Synergy, antagonism, and what the chequerboard puts between them.

PMID- 12805254
TI  - Streptococcus pyogenes isolates with characterized macrolide resistance
      mechanisms in Spain: in vitro activities of telithromycin and cethromycin.
AB  - The in vitro activities of telithromycin and cethromycin (ABT-773) against 412
      Streptococcus pyogenes isolates, consecutively collected in 17 Spanish hospitals
      from different geographical areas, were evaluated and compared with those of
      erythromycin A, penicillin G, clindamycin and quinupristin-dalfopristin. With a
      susceptibility testing breakpoint of < or = 1 mg/L for both compounds, 96.1% of
      isolates were susceptible to telithromycin and 99.8% to cethromycin. Erythromycin
      non-susceptible isolates (intermediate plus resistant, MIC > or = 0.5 mg/L)
      comprised 23% of those tested, and were analysed for the genetic basis of their
      resistance by PCR. Among these isolates (n = 95), 72.6% harboured mef(A), 8.4%,
      erm(B), and 3.2%, erm(A), as sole macrolide resistance gene, whereas the presence
      of mef(A) plus erm(A) (11.6%) or mef(A) plus erm(B) (4.2%) was also observed.
      Both ketolides displayed a significant in vitro activity against S. pyogenes
      regardless of the macrolide resistance mechanisms. Nevertheless, in the case of
      telithromycin, 11 out of 19 of the erm(B)-positive isolates (2.7% of total
      population) exhibited an MIC range of 4-32 mg/L. According to the present
      results, telithromycin and cethromycin offer a wide coverage against S. pyogenes
      isolates in a geographic area with a high incidence of resistance to currently
      used macrolides.

PMID- 12805256
TI  - Macrolide resistance determinants of group A streptococci in Ankara, Turkey.
AB  - OBJECTIVES: Macrolide-lincosamide-streptogramin B (MLSB) resistance determinants
      of group A streptococci (GAS) in Ankara, Turkey, were defined for the first time.
      ISOLATES AND METHODS: A total of 1355 GAS isolates, collected from three
      different regions of Ankara, were screened for erythromycin resistance.
      Resistance phenotypes were determined by a triple-disc test, and the gene
      determinants responsible were determined by PCR. MICs of erythromycin,
      clindamycin and spiramycin were measured for the resistant isolates, and
      susceptibility rates to some further antibiotics were determined. RESULTS: Thirty
      six isolates (2.6%) were resistant to erythromycin. Of these, 17 (47.2%)
      expressed macrolide-restricted resistance (M phenotype), while the remainder
      expressed inducible (16 isolates, 44.4%) or constitutive (three isolates, 8.3%)
      MLSB resistance. All isolates of the M phenotype harboured the mef(A) gene. Of
      non-M isolates, 14 harboured erm(A) subclass erm(TR) and five had erm(B) genes.
      There was a significant relationship between tetracycline resistance and the
      inducible phenotype (P < 0.05). Macrolide resistance was significantly higher in
      adults (P < 0.05), and increased more than two-fold in 2002 compared with 2001 (P
      < 0.05). CONCLUSION: The prevalence of macrolide resistance in GAS is low in
      Ankara; therefore, routine antimicrobial susceptibility testing against these
      agents seems unwarranted.

PMID- 12805257
TI  - Evolution of an integron carrying blaVIM-2 in Eastern Europe: report from the
      SENTRY Antimicrobial Surveillance Program.
AB  - As part of the SENTRY Antimicrobial Surveillance Program, an imipenem-resistant
      Pseudomonas aeruginosa strain (81-11963A) was isolated from the blood culture of
      a female neonate institutionalized at the local children's hospital in Warsaw,
      Poland. Cloning of an imipenem resistance determinant revealed it to be a VIM-2
      metallo-beta-lactamase, but sequence analysis of DNA adjacent to blaVIM-2
      revealed it to have a unique gene context. Downstream of the blaVIM-2 gene
      resides an aacA4 gene encoding the AAC(6')-Ib aminoglycoside acetyltransferase.
      The integron containing blaVIM-2 shows high similarity to that reported from In58
      in France but was novel in that it possessed a gene cassette with a 59 truncated
      base element only 19 base pairs (bp) long, consisting of a conserved core site
      and an inverse core site separated by only 5 bp. This appears to be the first
      report of a metallo-beta-lactamase gene arising from a pathogenic strain in
      Eastern Europe.

PMID- 12805258
TI  - Criteria of time and antibiotic susceptibility in the elimination of duplicates
      when calculating resistance frequencies.
AB  - We studied the effects of various systems of eliminating repeat isolates on the
      absolute number and susceptibility of Pseudomonas aeruginosa, Acinetobacter
      baumannii and Staphylococcus aureus isolates over a 2 year period. The criterion
      of time is objective and reproducible, whereas that of variation in antibiotic
      susceptibility detects variations in the susceptibility of microorganisms that
      acquire resistance during treatment, but may be affected by methodological errors
      in determining the antibiotic susceptibility. These tools are useful in the
      control of multi-resistant bacteria and enable the true situation regarding
      antibiotic resistance in each geographical area to be determined.

PMID- 12805259
TI  - Penicillin-binding proteins involved in high-level piperacillin resistance in
      Veillonella spp.
AB  - OBJECTIVES: To investigate high-level piperacillin resistance in Veillonella spp.
      in the absence of beta-lactamase activity. METHODS: Penicillin-binding protein
      (PBP) competition studies were conducted in Veillonella strains, with
      piperacillin MICs ranging from 0.5 to >128 mg/L and ampicillin MICs from 0.125 to
      4 mg/L. Whole cell lysates were pre-incubated with piperacillin or ampicillin and
      post-labelled with [3H]benzylpenicillin. RESULTS: PBP competition studies showed
      that the PBP with greatest affinity for penicillin and ampicillin had a molecular
      weight of approximately 66 kDa, and exhibited reduced binding of piperacillin in
      resistant strains. CONCLUSIONS: This unusual focusing of different penicillins on
      one PBP may be the cause of selective mutants resulting from piperacillin MICs >
      128 mg/L. In the absence of beta-lactamases, alterations in penicillin-binding
      were seen to be major contributors to high-level piperacillin resistance
      development.

PMID- 12805260
TI  - Evaluation of commercial assays for vancomycin and aminoglycosides in serum: a
      comparison of accuracy and precision based on external quality assessment.
AB  - OBJECTIVE: To compare the accuracy and precision of commercial assay techniques
      in the measurement of gentamicin, tobramycin, amikacin, netilmicin and vancomycin
      in serum. METHODS: Data from the measurement of 40 external quality assessment
      samples from 358 laboratories providing a therapeutic drug monitoring service
      were analysed. RESULTS: Significant differences between techniques in accuracy
      and precision were observed for all drugs. Coefficients of variation ranged from
      4.1% to 9.8% for the aminoglycosides and from 6.7% to 11.7% for vancomycin. The
      percentage difference in measurements from the weighed-in drug concentration
      ranged from -10.1% to +4.0% for the aminoglycosides and from -3.5% to +5.7% for
      vancomycin. The Dade Behring Emit immunoassay was notable in producing
      significantly more outliers (>4 S.D. from the weighed-in concentration) than
      other techniques in the measurement of gentamicin, amikacin and vancomycin.
      CONCLUSIONS: All assays performed to a satisfactory standard for measurement in
      non-renal patients, but none met the more stringent standards desirable for
      monitoring patients with renal impairment.

PMID- 12805261
TI  - DHFR and DHPS genotypes of Plasmodium falciparum isolates from Gabon correlate
      with in vitro activity of pyrimethamine and cycloguanil, but not with sulfadoxine
      pyrimethamine treatment efficacy.
AB  - OBJECTIVES: To assess the relationship between the presence of DHFR and DHPS
      mutations in Plasmodium falciparum, parasite in vitro resistance, and in vivo
      efficacy of sulfadoxine-pyrimethamine (SP) treatment. PATIENTS AND METHODS:
      Measurement of SP treatment efficacy in malaria-infected children in Gabon was
      combined with in vitro tests of susceptibility to pyrimethamine and cycloguanil,
      and molecular genotyping at several DHFR and DHPS loci of parasites isolated
      before treatment. DHFR was studied at codons 108, 51, and 59, whereas DHPS gene
      was typed at positions 436, 437, 540 and 581. RESULTS: SP treatment was effective
      in 86% of children by day 28. Seventy-five percent of isolates were in vitro
      resistant to pyrimethamine and 65.5% to cycloguanil. No mutation was detected at
      codons 540 and 581 of the DHPS gene. Most isolates (71.8%) presented with the
      triple mutant DHFR genotype, whereas 64.3% combined at least three DHFR and one
      DHPS mutations. The increase in the number of DHFR mutations was associated with
      an increase in in vitro resistance to pyrimethamine and cycloguanil; three DHFR
      mutations conferred pyrimethamine and to a lesser extent cycloguanil resistance.
      Treatment failures only occurred with isolates presenting at least two DHFR
      mutations (S108N and C59R) and one DHPS mutation (S436A or A437G), but SP
      treatment of infections with such parasites gave treatment success in 82.0% of
      children. CONCLUSIONS: DHFR mutations that lead to high-level in vitro resistance
      to pyrimethamine plus 1-2 DHPS mutations are not sufficient to induce in vivo
      failure of SP treatment in young children from Gabon.

PMID- 12805262
TI  - Significance of antibiotics in the environment.

PMID- 12805263
TI  - Accumulation and activity of cethromycin (ABT-773) within human polymorphonuclear
      leucocytes.
AB  - OBJECTIVES: To evaluate the penetration of ketolide cethromycin (ABT-773) into
      human polymorphonuclear leucocytes (PMNs) and its intracellular activity.
      METHODS: The uptake of radiolabelled cethromycin by PMNs was determined by a
      velocity gradient centrifugation technique. The activity of cethromycin against
      intracellular Staphylococcus aureus ATCC 25923 in PMNs was also evaluated.
      RESULTS: The cellular to extracellular concentration (C/E) ratio for cethromycin
      was >200 at an extracellular concentration of 2 mg/L. The uptake of cethromycin
      into PMNs was rapid and saturable. Cethromycin was slowly released from the
      loaded PMNs (cell associated drug>50% after 2 h of incubation). Intracellular
      penetration was significantly affected by the environmental temperature (C/E
      ratio at 4 degrees C and 37 degrees C: 13 +/- 6 and 226 +/- 31, respectively; P <
      0.05), by cell viability (C/E ratio for dead and viable cells: 100 +/- 38 and 226
      +/- 31, respectively; P < 0.05), by pH (C/E ratio was significantly increased at
      basic pH) and by the metabolic inhibitors 2,4-dinitrophenol and carbonyl cyanide
      m-chlorophenylhydrazone. The intracellular accumulation of cethromycin also
      decreased significantly when cells were activated with phorbol myristate acetate
      or opsonized zymosan. These data indicate that a potentially active mechanism
      could be involved in the uptake of cethromycin by PMNs. At high extracellular
      concentrations of 5 and 10 mg/L, cethromycin showed significant intracellular
      activity against S. aureus. CONCLUSIONS: Cethromycin achieves high intracellular
      concentrations within human PMNs, remaining active intracellularly.

PMID- 12805264
TI  - In vitro activity of tigecycline (GAR-936), a novel glycylcycline, against
      vancomycin-resistant enterococci and staphylococci with diminished susceptibility
      to glycopeptides.

PMID- 12805265
TI  - The in vitro activity of daptomycin against Staphylococcus aureus and
      Enterococcus species.
AB  - OBJECTIVE: The purpose of this study was to examine the in vitro activity of
      daptomycin using an optimal calcium (Ca2+) concentration (50 mg/L) against a
      diverse collection of enterococcal and Staphylococcus aureus clinical isolates,
      including glycopeptide-resistant enterococci (GRE) and methicillin-resistant S.
      aureus (MRSA). METHODS: The activity of daptomycin was compared with the
      activities of seven other agents against 1483 enterococcal and S. aureus clinical
      isolates, including 303 GRE and 193 methicillin-resistant S. aureus (MRSA)
      strains. Susceptibility testing was performed by the NCCLS broth microdilution
      method, with one exception: Mueller-Hinton (MH) broth was supplemented to a
      physiological level of 50 mg/L Ca2+ when testing daptomycin. Daptomycin zone
      diameters were determined by disc diffusion with MH agar plates containing Ca2+
      50 mg/L. RESULTS: All staphylococcal isolates tested, and the majority of
      enterococcal isolates (96.5%), would be considered susceptible to daptomycin if
      the breakpoint previously proposed of </=2 mg/L was applied. The activity of
      daptomycin against MRSA and methicillin-susceptible S. aureus was essentially
      equal. Daptomycin also had similar activity against GRE and glycopeptide
      susceptible enterococci. Every S. aureus isolate had a daptomycin zone diameter >
      or = 20 mm, and all of the enterococcal isolates had daptomycin zone diameters >
      or = 17 mm. CONCLUSIONS: Overall, daptomycin showed potent activity against S.
      aureus and enterococcal isolates, comparable to quinupristin-dalfopristin and
      linezolid.

PMID- 12805266
TI  - Cross-resistance and associated resistance in 2478 Escherichia coli isolates from
      the Pan-European ECO.SENS Project surveying the antimicrobial susceptibility of
      pathogens from uncomplicated urinary tract infections.
AB  - The antimicrobial resistance profiles, comprising 12 antibiotics, of 2478
      isolates of Escherichia coli from the ECO.SENS Project involving women with acute
      uncomplicated urinary tract infection at 252 community health care centres in 17
      countries were determined. Resistance to ampicillin alone (6.3%) and
      sulfamethoxazole alone (5.4%) were the most common 'single resistances'. Multiple
      resistance was most common in Spain and least common in Finland. The main
      associated-resistance profiles involved ampicillin/sulfamethoxazole (8.7%) and
      ampicillin/sulfamethoxazole/trimethoprim/trimethoprim-sulfamethoxazole (6.4%).
      The most common profile of multiple resistance was
      ampicillin/sulfamethoxazole/trimethoprim/trimethoprim-sulfamethoxazole/nalidixic
      acid/ciprofloxacin. Twenty-one isolates, half of which came from Spain, were
      resistant to seven antibiotics or more. Three isolates, one from Spain and two
      from Portugal, were resistant to nine of the 12 antibiotics investigated.

PMID- 12805267
TI  - The mutant selection window and antimicrobial resistance.
AB  - The mutant selection window is an antimicrobial concentration range extending
      from the minimal concentration required to block the growth of wild-type bacteria
      up to that required to inhibit the growth of the least susceptible, single-step
      mutant. The upper boundary is also called the mutant prevention concentration
      (MPC). Placing antimicrobial concentrations inside the window is expected to
      enrich resistant mutant subpopulations selectively, whereas placing
      concentrations above the window is expected to restrict selective enrichment.
      Since window dimensions are characteristic of each pathogen-antimicrobial
      combination, they can be linked with antimicrobial pharmacokinetics to rank
      compounds and dosing regimens in terms of their propensity to enrich mutant
      fractions of bacterial populations. For situations in which antimicrobial
      concentrations cannot be kept above the window, restricting the enrichment of
      mutants requires combination therapy.

PMID- 12805268
TI  - Effect of chloramphenicol, erythromycin, moxifloxacin, penicillin and
      tetracycline concentration on the recovery of resistant mutants of Mycobacterium
      smegmatis and Staphylococcus aureus.
AB  - The effect of antimicrobial concentration on colony-forming ability of resistant
      mutant subpopulations of Mycobacterium smegmatis and Staphylococcus aureus was
      measured for chloramphenicol, erythromycin, moxifloxacin, penicillin and
      tetracycline. The relationship between drug concentration and the recovery of
      mutant colonies was distinct for each bacterium-antimicrobial combination;
      however, in each case application of large numbers of cells to drug-containing
      agar plates revealed a progressive reduction in mutant recovery as antimicrobial
      concentration increased. The minimal concentration that allowed no mutant
      recovery from more than 10(10) input cells was measured to estimate the minimum
      inhibitory concentration (MIC) of the least susceptible, single-step mutant
      subpopulation, a parameter also called the mutant prevention concentration (MPC).
      These data expand the number of antimicrobial-bacterial combinations for which a
      mutant selection window can be measured.

PMID- 12805269
TI  - Comparative pharmacokinetics and safety of a novel lyophilized amphotericin B
      lecithin-based oil-water microemulsion and amphotericin B deoxycholate in animal
      models.
AB  - Amphotericin B (AmB) has been a most effective systemic antifungal agent, but its
      use is circumscribed by the dose-limiting toxicity of the conventional micellar
      dispersion formulation Fungizone (D-AmB). To lower AmB-associated toxicity, AmB
      may be integrated into oil-in-water lecithin-based microemulsions. The present
      study compares the pharmacokinetic characteristics of D-AmB with the alternative
      formulation of AmB in microemulsion (M-AmB), which has proved effective in a
      murine candidiasis model. Both formulations were given by intravenous bolus: D
      AmB 1 mg/kg, and M-AmB 0.5, 1 or 2 mg/kg. The pharmacokinetics of D-AmB and M-AmB
      have several differences, specifically with regard to the respective Cmax and
      AUC0- infinity values. Elimination of AmB from serum was biphasic for both M-AmB
      and D-AmB. Single-dose D-AmB (1 mg/kg) achieved a Cmax of 3.89 +/- 0.48 mg/L and
      an AUC0- infinity of 32.28 +/- 7.31 mg.h/L, whereas single-dose M-AmB (1 mg/kg)
      by comparison achieved a lower Cmax (2.92 +/- 0.54 mg/L) and a lower AUC0-
      infinity (21.89 +/- 5.17 mg.h/L). To evaluate the safety of M-AmB, a multiple
      dose toxicity study was performed in groups of 10 mice, each receiving D-AmB 1
      mg/kg, or M-AmB 1, 1.5, 2 or 3 mg/kg. The findings suggest that, in comparison
      with D-AmB, M-AmB produces no histologically demonstrable renal lesions, or
      changes in clinical chemistry.

PMID- 12805270
TI  - Spotted long oligonucleotide arrays for human gene expression analysis.
AB  - DNA microarrays produced by deposition (or 'spotting')of a single long
      oligonucleotide probe for each gene may be an attractive alternative to other
      types of arrays. We produced spotted oligonucleotide arrays using two large
      collections of approximately 70-mer probes, and used these arrays to analyze gene
      expression in two dissimilar human RNA samples. These samples were also analyzed
      using arrays produced by in situ synthesis of sets of multiple short (25-mer)
      oligonucleotides for each gene (Affymetrix GeneChips). We compared expression
      measurements for 7344 genes that were represented in both long oligonucleotide
      probe collections and the in situ-synthesized 25-mer arrays. We found strong
      correlations (r = 0.8-0.9) between relative gene expression measurements made
      with spotted long oligonucleotide probes and in situ-synthesized 25-mer probe
      sets. Spotted long oligonucleotide arrays were suitable for use with both
      unamplified cDNA and amplified RNA targets, and are a cost-effective alternative
      for many functional genomics applications. Most previously reported evaluations
      of microarray technologies have focused on expression measurements made on a
      relatively small number of genes. The approach described here involves far more
      gene expression measurements and provides a useful method for comparing existing
      and emerging techniques for genome-scale expression analysis.

PMID- 12805271
TI  - Mechanisms of thermal adaptation revealed from the genomes of the Antarctic
      Archaea Methanogenium frigidum and Methanococcoides burtonii.
AB  - We generated draft genome sequences for two cold-adapted Archaea, Methanogenium
      frigidum and Methanococcoides burtonii, to identify genotypic characteristics
      that distinguish them from Archaea with a higher optimal growth temperature
      (OGT). Comparative genomics revealed trends in amino acid and tRNA composition,
      and structural features of proteins. Proteins from the cold-adapted Archaea are
      characterized by a higher content of noncharged polar amino acids, particularly
      Gln and Thr and a lower content of hydrophobic amino acids, particularly Leu.
      Sequence data from nine methanogen genomes (OGT 15 degrees -98 degrees C) were
      used to generate 1111 modeled protein structures. Analysis of the models from the
      cold-adapted Archaea showed a strong tendency in the solvent-accessible area for
      more Gln, Thr, and hydrophobic residues and fewer charged residues. A cold shock
      domain (CSD) protein (CspA homolog) was identified in M. frigidum, two
      hypothetical proteins with CSD-folds in M. burtonii, and a unique winged helix
      DNA-binding domain protein in M. burtonii. This suggests that these types of
      nucleic acid binding proteins have a critical role in cold-adapted Archaea.
      Structural analysis of tRNA sequences from the Archaea indicated that GC content
      is the major factor influencing tRNA stability in hyperthermophiles, but not in
      the psychrophiles, mesophiles or moderate thermophiles. Below an OGT of 60
      degrees C, the GC content in tRNA was largely unchanged, indicating that any
      requirement for flexibility of tRNA in psychrophiles is mediated by other means.
      This is the first time that comparisons have been performed with genome data from
      Archaea spanning the growth temperature extremes from psychrophiles to
      hyperthermophiles.

PMID- 12805272
TI  - Using advanced intercross lines for high-resolution mapping of HDL cholesterol
      quantitative trait loci.
AB  - Mapping quantitative trait loci (QTLs) with high resolution facilitates
      identification and positional cloning of the underlying genes. The novel approach
      of advanced intercross lines (AILs) generates many more recombination events and
      thus can potentially narrow QTLs significantly more than do conventional
      backcrosses and F2 intercrosses. In this study, we carried out QTL analyses in
      (C57BL/6J x NZB/BlNJ) x C57BL/6J backcross progeny fed either chow or an
      atherogenic diet to detect QTLs that regulate high-density lipoprotein
      cholesterol (HDL)concentrations, and in (C57BL/6J x NZB/BlNJ) F11 AIL progeny to
      confirm and narrow those QTLs. QTLs for HDL concentrations were found on
      chromosomes 1, 5, and 16. AIL not only narrowed the QTLs significantly more than
      did a conventional backcross but also resolved a chromosome 5 QTL identified in
      the backcross into two QTLs, the peaks of both being outside the backcross QTL
      region. We tested 27 candidate genes and found significant mRNA expression
      differences for 12 (Nr1i3, Apoa2, Sap, Tgfb2, Fgfbp1, Prom, Ppargc1, Tcf1, Ncor2,
      Srb1, App, and Ifnar). Some of these underlay the same QTL, indicating that
      expression differences are common and not sufficient to identify QTL genes. All
      the major HDL QTLs in our study had homologous counterparts in humans, implying
      that their underlying genes regulate HDL in humans.

PMID- 12805273
TI  - Systematic cloning of Treponema pallidum open reading frames for protein
      expression and antigen discovery.
AB  - A topoisomerase-based method was used to clone PCR products encoding 991 of the
      1041 open reading frames identified in the genome sequence of the bacterium that
      causes syphilis, Treponema pallidum subsp. pallidum. Cloning the open reading
      frames into the univector plasmid system permitted the rapid conversion of the
      original clone set to other functional vectors containing a variety of promoters
      or tag sequences. A computational prediction of signal sequences identified 248
      T. pallidum proteins that are potentially secreted from the cell. These clones
      were systematically converted into vectors designed to express the encoded
      proteins as glutathione-S-transferase fusion proteins. To test the potential of
      the clone set for novel antigen discovery, 85 of these fusion proteins were
      expressed from Escherichia coli, partially purified, and tested for antigenicity
      by using sera from rabbits infected with T. pallidum. Twelve of the 85 proteins
      bound significant levels of antibody. Of these 12 proteins, seven had previously
      been identified as T. pallidum antigens, and the remaining five represent novel
      antigens. These results demonstrate the potential of the T. pallidum clone set
      for antigen discovery and, more generally, for advancing the biology of this
      enigmatic spirochete.

PMID- 12805275
TI  - Analysis of mRNA with microsomal fractionation using a SAGE-based DNA microarray
      system facilitates identification of the genes encoding secretory proteins.
AB  - In the regulation of host defense responses such as inflammation and immunity,
      the secretory proteins, including membrane proteins, play central roles. Although
      many secretory proteins have been identified by using methods such as
      differential display, random screening, or the signal sequence trap method, each
      method suffers from poor reproducibility, low sensitivity, or time-consuming or
      laborious work. Therefore, the strategy for facilitating the selection of the
      genes encoding the secretory proteins is desired. In this paper, we describe a
      system for isolating the genes encoding secretory proteins by analyzing mRNAs
      with microsomal fractionation on serial analysis of gene expression (SAGE)-based
      DNA microarray system. This system succeeded in discriminating the genes encoding
      secretory proteins from ones encoding nonsecretory proteins with 80% accuracy. We
      applied this system to human T lymphocytes. As a result, we were able to identify
      the genes that are not only encoding secretory proteins but also expressing
      selectively in a specific subset of T lymphocytes. The SAGE-based DNA microarray
      system is a promising system to identify the genes encoding specific secretory
      proteins.

PMID- 12805276
TI  - An active non-LTR retrotransposon with tandem structure in the compact genome of
      the pufferfish Tetraodon nigroviridis.
AB  - The fish retrotransposable element Zebulon encodes a reverse transcriptase and a
      carboxy-terminal restriction enzyme-like endonuclease, and is related
      phylogenetically to site-specific non-LTR retrotransposons from nematodes.
      Zebulon was detected in the pufferfishes Tetraodon nigroviridis and Takifugu
      rubripes, as well as in the zebrafish Danio rerio. Structural analysis suggested
      that Zebulon, in contrast to most non-LTR retrotransposons, might be able to
      retrotranspose as a partial tandem array. Zebulon was active relatively recently
      in the compact genome of T. nigroviridis, in which it contributed to the
      extension of intergenic and intronic sequences, and possibly to the formation of
      genomic rearrangements. Accumulation of Zebulon together with other
      retrotransposons was observed in some heterochromatic chromosomal regions of the
      genome of T. nigroviridis that might serve as reservoirs for active elements.
      Hence, pufferfish compact genomes are not evolutionarily inert and contain active
      retrotransposons, suggesting the presence of mechanisms allowing accumulation of
      retrotransposable elements in heterochromatin, but minimizing their impact on
      euchromatic regions. Homologous recombination between partial tandem sequences
      eliminating active copies of Zebulon and reducing the size of insertions in
      intronic and intragenic regions might represent such a mechanism.

PMID- 12805278
TI  - Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in
      vivo.
AB  - Hair cell loss in the mammalian cochlea is irreversible and results in permanent
      hearing loss. Math1, the basic helix-loop-helix transcription factor homolog of
      the Drosophila atonal gene, is a positive regulator of hair cell differentiation
      during cochlear development. Developing hair cells express Math1, and nonsensory
      cells do not. We set out to determine the outcome of overexpression of Math1 in
      nonsensory cells of the cochlea on the phenotype of these cells. We demonstrate
      that in vivo inoculation of adenovirus with the Math1 gene insert into the
      endolymph of the mature guinea pig cochlea results in Math1 overexpression in
      nonsensory cochlear cells, as evident from the presence of Math1 protein in
      supporting cells of the organ of Corti and in adjacent nonsensory epithelial
      cells. Math1 overexpression leads to the appearance of immature hair cells in the
      organ of Corti and new hair cells adjacent to the organ of Corti in the
      interdental cell, inner sulcus, and Hensen cell regions. Axons are extended from
      the bundle of auditory nerve toward some of the new hair cells, suggesting that
      the new cells attract auditory neurons. We conclude that nonsensory cells in the
      mature cochlea retain the competence to generate new hair cells after
      overexpression of Math1 in vivo and that Math1 is necessary and sufficient to
      direct hair cell differentiation in these mature nonsensory cells.

PMID- 12805277
TI  - Genetic variation among world populations: inferences from 100 Alu insertion
      polymorphisms.
AB  - We examine the distribution and structure of human genetic diversity for 710
      individuals representing 31 populations from Africa, East Asia, Europe, and India
      using 100 Alu insertion polymorphisms from all 22 autosomes. Alu diversity is
      highest in Africans (0.349) and lowest in Europeans (0.297). Alu insertion
      frequency is lowest in Africans (0.463) and higher in Indians (0.544), E. Asians
      (0.557), and Europeans (0.559). Large genetic distances are observed among
      African populations and between African and non-African populations. The root of
      a neighbor-joining network is located closest to the African populations. These
      findings are consistent with an African origin of modern humans and with a
      bottleneck effect in the human populations that left Africa to colonize the rest
      of the world. Genetic distances among all pairs of populations show a significant
      product-moment correlation with geographic distances (r = 0.69, P < 0.00001).
      F(ST), the proportion of genetic diversity attributable to population subdivision
      is 0.141 for Africans/E. Asians/Europeans, 0.047 for E. Asians/Indians/Europeans,
      and 0.090 for all 31 populations. Resampling analyses show that approximately 50
      Alu polymorphisms are sufficient to obtain accurate and reliable genetic distance
      estimates. These analyses also demonstrate that markers with higher F(ST) values
      have greater resolving power and produce more consistent genetic distance
      estimates.

PMID- 12805274
TI  - Identification of promoter regions in the human genome by using a retroviral
      plasmid library-based functional reporter gene assay.
AB  - Attempts to identify regulatory sequences in the human genome have involved
      experimental and computational methods such as cross-species sequence comparisons
      and the detection of transcription factor binding-site motifs in coexpressed
      genes. Although these strategies provide information on which genomic regions are
      likely to be involved in gene regulation, they do not give information on their
      functions. We have developed a functional selection for promoter regions in the
      human genome that uses a retroviral plasmid library-based system. This approach
      enriches for and detects promoter function of isolated DNA fragments in an in
      vitro cell culture assay. By using this method, we have discovered likely
      promoters of known and predicted genes, as well as many other putative promoter
      regions based on the presence of features such as CpG islands. Comparison of
      sequences of 858 plasmid clones selected by this assay with the human genome
      draft sequence indicates that a significantly higher percentage of sequences
      align to the 500-bp segment upstream of the transcription start sites of known
      genes than would be expected from random genomic sequences. We also observed
      enrichment for putative promoter regions of genes predicted in at least two
      annotation databases and for clones overlapping with CpG islands. Functional
      validation of randomly selected clones enriched by this method showed that a
      large fraction of these putative promoters can drive the expression of a reporter
      gene in transient transfection experiments. This method promises to be a useful
      genome-wide function-based approach that can complement existing methods to look
      for promoters.

PMID- 12805279
TI  - Mouse NG2+ oligodendrocyte precursors express mRNA for proteolipid protein but
      not its DM-20 variant: a study of laser microdissection-captured NG2+ cells.
AB  - Despite recent advances in our understanding of lineage of oligodendrocytes,
      detailed molecular characterization of this lineage in vivo is limited, primarily
      because of our inability to obtain a pure population of cells in situ. To define
      the molecular characteristics of oligodendrocyte lineage cells during development
      and their response to injury, we developed a strategy that uses laser capture
      microdissection (LCM) to isolate cells from sections and reverse transcription
      PCR to determine mRNA expression. As a first step, we examined the expression of
      myelin-specific protein genes in NG2+ cells in cerebral cortex. We demonstrate
      that NG2+ cells in both developing and adult mice express NG2 mRNA but not mRNA
      for proteins specific for astrocytes, neurons, or microglia, indicating that a
      highly pure population of antigen-specific cells of the oligodendrocyte lineage
      can be obtained using LCM. Furthermore, we show that NG2+ cells express mRNAs for
      proteolipid protein (PLP), myelin basic protein, and 2',3'-cyclic nucleotide 3'
      phosphodiesterase, but they dot not express DM-20 mRNA, a PLP mRNA splicing
      variant. Our data demonstrate that antigen-specific cells of oligodendrocyte
      lineage differentially express mRNA for myelin-specific proteins and their
      variants in vivo, partly define the gene expression in NG2+ cells, and raise
      questions about the cellular sites of DM-20 expression. This work also shows that
      LCM is a valuable tool to define and analyze gene expression in the cells of the
      oligodendrocyte lineage.

PMID- 12805280
TI  - Exposure to acute stress blocks the induction of long-term potentiation of the
      amygdala-prefrontal cortex pathway in vivo.
AB  - In recent years, attention has been given to the interaction between the
      emotional state of the animal and its ability to learn and remember. Studies into
      the neural mechanisms underlying these interactions have focused on stress
      induced synaptic plasticity impairments in the hippocampus. However, other brain
      areas, including the amygdala and the prefrontal cortex (PFC), have been
      implicated in relation to stress-mediated effects on memory. The present study
      examined whether stress, which impairs hippocampal long-term potentiation (LTP),
      also affects LTP of the basolateral amygdala (BLA)-PFC pathway in vivo. We first
      confirmed that the stress protocol we used, i.e., the elevated platform stress,
      was effective in blocking LTP in the CA1 area of the hippocampus. We then
      characterized activity and established the ability to induce LTP at the BLA-PFC
      pathway. Finally, we examined the effects of an exposure to the elevated platform
      stress on the ability to induce LTP in this pathway. The results indicate that,
      at the same time when LTP is blocked in the hippocampus, it is also inhibited in
      the BLA-medial PFC pathway. These results call for a shift from a focused
      attention on the effects of stress on plasticity in the hippocampus to a system
      level approach that emphasizes the possible modification of interactions between
      relevant brain areas after an exposure to a stressful experience.

PMID- 12805281
TI  - Elevation of basal intracellular calcium as a central element in the activation
      of brain macrophages (microglia): suppression of receptor-evoked calcium
      signaling and control of release function.
AB  - Microglia-brain macrophages are immune-competent cells of the CNS and respond to
      pathologic events. Using bacterial lipopolysaccharide (LPS) as a tool to activate
      cultured mouse microglia, we studied alterations in the intracellular calcium
      concentration ([Ca 2+]i) and in the receptor-evoked generation of transient
      calcium signals. LPS treatment led to a chronic elevation of basal [Ca 2+]i along
      with a suppression of evoked calcium signaling, as indicated by reduced [Ca 2+]i
      transients during stimulation with UTP and complement factor 5a. Presence of the
      calcium chelator BAPTA prevented the activation-associated changes in [Ca 2+]i
      and restored much of the signaling efficacy. We also evaluated downstream
      consequences of a basal [Ca 2+]i lifting during microglial activation and found
      BAPTA to strongly attenuate the LPS-induced release of nitric oxide (NO) and
      certain cytokines and chemokines. Furthermore, microglial treatment with
      ionomycin, an ionophore elevating basal [Ca 2+]i, mimicked the activation-induced
      calcium signal suppression but failed to induce release activity on its own. Our
      findings suggest that chronic elevation of basal [Ca 2+]i attenuates receptor
      triggered calcium signaling. Moreover, increased [Ca 2+]i is required, but by
      itself is not sufficient, for release of NO and certain cytokines and chemokines.
      Elevation of basal [Ca 2+]i could thus prove a central element in the regulation
      of executive functions in activated microglia.

PMID- 12805282
TI  - Brain-derived neurotrophic factor protection of cortical neurons from serum
      withdrawal-induced apoptosis is inhibited by cAMP.
AB  - Programmed cell death plays an important role both during the development of the
      CNS and in its homeostasis throughout adulthood. A complex balance between cell
      death- and survival-inducing signals determines the fate of individual neurons.
      Intracellular cAMP is thought to regulate neuronal survival, and previous studies
      have shown that the survival of retinal ganglion cells by brain-derived
      neurotrophic factor (BDNF) is dependent on cAMP. Here we report the surprising
      observation that cAMP attenuates the ability of BDNF to rescue cortical neurons
      from apoptosis after serum deprivation, a process mediated via the
      phosphatidylinositol 3 (PI3)-kinase signal transduction cascade. Depolarization
      by KCl, which increases cAMP in cortical neurons, also attenuates BDNF protection
      against serum withdrawal. Our data indicate that cAMP antagonizes neurotrophin
      protection from serum withdrawal by inhibiting the PI3-kinase signal transduction
      cascade. This study indicates that cAMP may inhibit some forms of neurotrophin
      mediated neuronal survival and suggests that a number of PI3-kinase-regulated
      processes in neurons may be inhibited by cAMP.

PMID- 12805283
TI  - Neocortical long-term potentiation and experience-dependent synaptic plasticity
      require alpha-calcium/calmodulin-dependent protein kinase II autophosphorylation.
AB  - Experience-dependent plasticity can be induced in the barrel cortex by removing
      all but one whisker, leading to potentiation of the neuronal response to the
      spared whisker. To determine whether this form of potentiation depends on
      synaptic plasticity, we studied long-term potentiation (LTP) and sensory-evoked
      potentials in the barrel cortex of alpha-calcium/calmodulin-dependent protein
      kinase II (alphaCaMKII)T286A mutant mice. We studied three different forms of LTP
      induction: theta-burst stimulation, spike pairing, and postsynaptic
      depolarization paired with low-frequency presynaptic stimulation. None of these
      protocols produced LTP in alphaCaMKIIT286A mutant mice, although all three were
      successful in wild-type mice. To study synaptic plasticity in vivo, we measured
      sensory-evoked potentials in the barrel cortex and found that single-whisker
      experience selectively potentiated synaptic responses evoked by sensory
      stimulation of the spared whisker in wild types but not in alphaCaMKIIT286A mice.
      These results demonstrate that alphaCaMKII autophosphorylation is required for
      synaptic plasticity in the neocortex, whether induced by a variety of LTP
      induction paradigms or by manipulation of sensory experience, thereby
      strengthening the case that the two forms of plasticity are related.

PMID- 12805284
TI  - Differential frequency dependence of P2Y1- and P2Y2- mediated Ca 2+ signaling in
      astrocytes.
AB  - ATP is a key extracellular messenger that mediates the propagation of Ca 2+ waves
      in astrocyte networks in various regions of the CNS. ATP-mediated Ca 2+ signals
      play critical roles in astrocyte proliferation and differentiation and in
      modulating neuronal activity. The actions of ATP on astrocytes are via two
      distinct subtypes of P2Y purinoceptors, P2Y1 and P2Y2 receptors (P2Y1Rs and
      P2Y2Rs), G-protein coupled receptors that stimulate mobilization of intracellular
      Ca 2+ ([Ca 2+]i) via the phospholipase Cbeta-IP3 pathway. We report here that
      P2Y1R-mediated and P2Y2R-mediated Ca 2+ responses differentially show two forms
      of activity-dependent negative feedback. First, Ca 2+ responses mediated by
      either receptor exhibit slow depression that is independent of stimulation
      frequency. Second, responses mediated by P2Y1Rs, but not those mediated by
      P2Y2Rs, show rapid oscillations after high-frequency stimulation. We demonstrate
      that the oscillations are mediated by recruiting negative feedback by protein
      kinase C, and we map the site responsible for the effect of protein kinase C to
      Thr339 in the C terminus of P2Y1R. We propose that frequency-dependent changes in
      ATP-mediated Ca 2+ signaling pathways may modulate astrocyte function and
      astrocyte-neuron signaling in the CNS.

PMID- 12805285
TI  - ATP acts via P2Y1 receptors to stimulate acetylcholinesterase and acetylcholine
      receptor expression: transduction and transcription control.
AB  - At the vertebrate neuromuscular junction ATP is known to stabilize acetylcholine
      in the synaptic vesicles and to be co-released with it. We have shown previously
      that a nucleotide receptor, the P2Y1 receptor, is localized at the junction, and
      we propose that this mediates a trophic role for synaptic ATP there. Evidence in
      support of this and on its mechanism is given here. With the use of chick or
      mouse myotubes expressing promoter-reporter constructs from genes of
      acetylcholinesterase (AChE) or of the acetylcholine receptor subunits, P2Y1
      receptor agonists were shown to stimulate the transcription of each of those
      genes. The pathway to activation of the AChE gene was shown to involve protein
      kinase C and intracellular Ca 2+ release. Application of dominant-negative or
      constitutively active mutants, or inhibitors of specific kinases, showed that it
      further proceeds via some of the known intermediates of extracellular signal
      regulated kinase phosphorylation. In both chick and mouse myotubes this
      culminates in activation of the transcription factor Elk-1, confirmed by gel
      mobility shift assays and by the nuclear accumulation of phosphorylated Elk-1.
      All of the aforementioned activations by agonist were amplified when the content
      of P2Y1 receptors was boosted by transfection, and the activations were blocked
      by a P2Y1-selective antagonist. Two Elk-1 binding site sequences present in the
      AChE gene promoter were jointly sufficient to drive ATP-induced reporter gene
      transcription. Thus ATP regulates postsynaptic gene expression via a pathway to a
      selective transcription factor activation.

PMID- 12805286
TI  - Serotonin drives a novel GABAergic synaptic current recorded in rat cerebellar
      purkinje cells: a Lugaro cell to Purkinje cell synapse.
AB  - We recorded a novel fast GABAergic synaptic current in cerebellar Purkinje cells
      in rat brain slices using patch-clamp techniques. Because of a relatively low
      sensitivity to bicuculline, these currents can be recorded under conditions in
      which basket and stellate cell inputs are blocked. The observations that the
      novel synaptic currents occur spontaneously only in the presence of serotonin,
      and the specific limited positions in the slice from which they can be
      electrically evoked, suggest that the presynaptic cell is the Lugaro cell. Cell
      attached recordings confirm that the Lugaro cell is the only interneuron in the
      cerebellar cortex with firing behavior consistent with the spontaneous activity
      recorded in Purkinje cells. The input shows a strong presynaptic modulation
      mediated by GABA(A) receptors, resulting in a dynamic range from almost 0 to >90%
      release probability. Modeling GABA(A) receptor responses to different GABA
      transients suggests that the relatively low sensitivity of the synaptic currents
      to bicuculline, compared with the higher affinity GABA(A) receptor antagonist SR
      95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl) pyridazinium), is
      attributable to an unusually long GABA dwell time and/or high GABA concentration
      in the synaptic cleft. The significance of this novel input is discussed in
      relation to other GABAergic synapses impinging on Purkinje cells. We suggest that
      the release of GABA onto Purkinje cells from Lugaro cells would primarily occur
      during motor activity under conditions in which the activity of basket and
      stellate cells might be inhibited.

PMID- 12805287
TI  - A mutation in the human norepinephrine transporter gene (SLC6A2) associated with
      orthostatic intolerance disrupts surface expression of mutant and wild-type
      transporters.
AB  - The norepinephrine transporter (NET) mediates reuptake of norepinephrine released
      from neurons, and, as such, it is an important regulator of noradrenergic
      neurotransmission. Recently, our laboratory reported a polymorphism in the human
      NET (hNET) gene A457P in an individual with the autonomic disorder orthostatic
      intolerance (OI). The presence of the hNET-A457P allele tracked with elevated
      heart rates and plasma NE levels in family members. hNET-A457P lacks >98%
      transport activity in several heterologous expression systems. In the present
      work, Western blot and biotinylation analyses performed in transiently
      transfected COS-7 cells revealed impairment in processing of hNET-A457P to the
      fully glycosylated form and a decrease in surface expression to approximately 30%
      of hNET-wild type (hNET-wt). Because the hNET-A457P mutation is carried on a
      single allele in OI subjects, we examined the influence of cotransfection of hNET
      wt and hNET-A457P and found that hNET-A457P exerts a dominant-negative effect on
      hNET-wt uptake activity. Experiments to determine oligomerization as a potential
      mechanism of the dominant-negative effect demonstrated that hNET-A457P
      coimmunoprecipitates with, and diminishes surface expression of, hNET-wt. These
      results reveal that hNET-A457P causes a conformational disruption that interferes
      with transporter biosynthetic progression and trafficking of both the mutant
      transporter and hNET-wt. These results elucidate a molecular mechanism for the
      disrupted NE homeostasis and cardiovascular function evident in OI patients with
      the hNET-A457P mutation.

PMID- 12805288
TI  - A role for the basal forebrain cholinergic system in estrogen-induced
      disinhibition of hippocampal pyramidal cells.
AB  - Estrogen transiently disinhibits hippocampal CA1 pyramidal cells in adult female
      rats and prolongs the decay time of IPSCs in these cells. Estrogen-induced
      changes in synaptic inhibition are likely to be causally related to subsequent
      enhancements in excitatory synaptic function in CA1 pyramidal cells. Currently,
      it is unknown how or on what cells estrogen acts to regulate synaptic inhibition
      in the hippocampus. We used whole-cell voltage-clamp recording of synaptically
      evoked IPSCs, spontaneous IPSCs, and miniature IPSCs in CA1 pyramidal cells to
      evaluate estrogen-induced changes in synaptic inhibition in ovariectomized rats
      that either were pretreated with the estrogen receptor (ER) antagonist tamoxifen
      or in which basal forebrain cholinergic neurons were eliminated by previous
      infusion of 192IgG-saporin toxin into the medial septum. We found that estrogen
      induced disinhibition and prolongation of IPSCs are entirely dependent on a
      tamoxifen-sensitive ER. Estrogen-induced disinhibition is partially dependent on
      basal forebrain cholinergic neurons, but the prolongation of IPSCs is not at all
      dependent on these cells. Paired-pulse experiments and recordings of action
      potential-related spontaneous IPSCs suggest that estrogen-induced disinhibition
      is associated with a decrease in probability of release at GABAergic synapses,
      which decreases the amplitude of IPSCs produced by inhibitory neuron action
      potentials. Our findings lend novel insights into estrogen regulation of
      inhibitory synapses in the hippocampus and point to estrogen action on basal
      forebrain cholinergic neurons as critically involved in mediating the effects of
      estrogen in the hippocampus.

PMID- 12805289
TI  - Selective breeding, quantitative trait locus analysis, and gene arrays identify
      candidate genes for complex drug-related behaviors.
AB  - Acute functional tolerance to ethanol develops during a single exposure to
      ethanol; it has been suggested to be a predisposing factor for the development of
      ethanol dependence. Genetic determinants of acute functional tolerance, as well
      as of ethanol dependence, have been clearly demonstrated. We describe a novel
      approach that uses a combination of selective breeding (to segregate genes
      contributing to the phenotype of interest, i.e., acute functional tolerance to
      the incoordinating effect of ethanol), quantitative trait locus analysis (to
      define chromosomal regions associated with acute functional tolerance), and DNA
      microarray technology (to identify differentially expressed genes in the brains
      of the selected lines of mice) to identify candidate genes for the complex
      phenotype of ethanol tolerance. The results indicate the importance of a signal
      transduction cascade that involves the glutamate receptor delta2 protein, the
      Ephrin B3 ligand, and the NMDA receptor, as well as a transcriptional regulatory
      protein that may be induced by activation of the NMDA receptor (zinc finger
      protein 179) and a protein that can modulate downstream responses to NMDA
      receptor activation (peroxiredoxin), in mediating acute tolerance to the
      incoordinating effect of ethanol.

PMID- 12805290
TI  - Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
AB  - Several lines of evidence indicate that alterations in axonal transport play a
      critical role in Alzheimer's disease (AD) neuropathology, but the molecular
      mechanisms that control this process are not understood fully. Recent work
      indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta
      (GSK3beta). In vivo, GSK3beta phosphorylates kinesin light chains (KLC) and
      causes the release of kinesin-I from membrane-bound organelles (MBOs), leading to
      a reduction in kinesin-I driven motility (Morfini et al., 2002b). To characterize
      a potential role for PS1 in the regulation of kinesin-based axonal transport, we
      used PS1-/- and PS1 knock-inM146V (KIM146V) mice and cultured cells. We show that
      relative levels of GSK3beta activity were increased in cells either in the
      presence of mutant PS1 or in the absence of PS1 (PS1-/-). Concomitant with
      increased GSK3beta activity, relative levels of KLC phosphorylation were
      increased, and the amount of kinesin-I bound to MBOs was reduced. Consistent with
      a deficit in kinesin-I-mediated fast axonal transport, densities of synaptophysin
      and syntaxin-I-containing vesicles and mitochondria were reduced in neuritic
      processes of KIM146V hippocampal neurons. Similarly, we found reduced levels of
      PS1, amyloid precursor protein, and synaptophysin in sciatic nerves of KIM146V
      mice. Thus PS1 appears to modulate GSK3beta activity and the release of kinesin-I
      from MBOs at sites of vesicle delivery and membrane insertion. These findings
      suggest that mutations in PS1 may compromise neuronal function by affecting GSK-3
      activity and kinesin-I-based motility.

PMID- 12805291
TI  - Kv3.1b is a novel component of CNS nodes.
AB  - We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the
      CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in
      a subset of nodes in the spinal cord, particularly those of large myelinated
      axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but
      does not colocalize with Na+ channels in initial segments. In the PNS, few nodes
      are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at
      nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal
      clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS
      dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even
      in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in
      vivo, indicating that these two proteins may interact in the CNS at nodes. 4
      Aminopyridine, a K+ channel blocker, broadened the compound action potential
      recorded from adult rat optic nerve and spinal cord, but not from the sciatic
      nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion,
      Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b
      does not account for the effects of 4-aminopyridine on central myelinated tracts.

PMID- 12805292
TI  - Inducible cAMP early repressor, an endogenous antagonist of cAMP responsive
      element-binding protein, evokes neuronal apoptosis in vitro.
AB  - Active CREB (cAMP responsive element-binding protein) transcription factor is
      crucial for neuronal survival. Several members of the CREM/ICER (cAMP responsive
      element modulator/inducible cAMP early repressor) protein family may act as
      endogenous CREB antagonists. However, their involvement in a process of
      programmed cell death remains unexplored. Here we report that ICER may play such
      a role in neuronal apoptosis because it is upregulated in apoptotic neurons in
      vitro, and overexpression of ICER, delivered in adenoviral vector, evokes
      programmed cell death of three different kinds of cultured neurons, namely those
      derived from hippocampal dentate gyrus, cerebral cortex, and superior cervical
      ganglion. Reporter gene assay with a promoter containing a CREB-responsive
      sequence revealed a decrease in both basal and induced CRE-dependent gene
      expression in neurons overexpressing ICER. Finally, the level of expression of
      the anti-apoptotic protein Bcl-2, a well known CREB target, was markedly
      diminished in ICER-treated neurons. We suggest that the naturally occurring CREB
      functional antagonist ICER may have a specific function in programmed cell death
      of neurons, probably by silencing the expression of anti-apoptotic genes.

PMID- 12805293
TI  - Coexpression of two visual pigments in a photoreceptor causes an abnormally broad
      spectral sensitivity in the eye of the butterfly Papilio xuthus.
AB  - The compound eye of the butterfly Papilio xuthus consists of three different
      types of ommatidia, each containing nine photoreceptor cells (R1-R9). We have
      found previously that the R5-R8 photoreceptors of type II ommatidia coexpress two
      different mRNAs, encoding opsins of green- and orange-red-absorbing visual
      pigments (Kitamoto et al., 1998). Do these cells contain two functionally
      distinct visual pigments? First, we identified the sensitivity spectrum of these
      photoreceptors by using combined intracellular recording and dye injection. We
      thus found that the R5-R8 of type II ommatidia have a characteristic sensitivity
      spectrum extending over an excessively broad spectral range, from the violet to
      the red region; the photoreceptors are therefore termed broadband photoreceptors.
      The spectral shape was interpreted with a computational model for type II
      ommatidia, containing a UV visual pigment in cells R1 and R2, two green visual
      pigments in cells R3 and R4, a far-UV-absorbing screening pigment (3
      hydroxyretinol) in the distal part of the ommatidium, and a red-screening pigment
      that surrounds the rhabdom. The modeling suggests that both visual pigments in
      the R5-R8 photoreceptors participate in phototransduction. This work provides the
      first compelling evidence that multiple visual pigments participate in
      phototransduction in single invertebrate photoreceptors.

PMID- 12805295
TI  - Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein
      reporter gene reveal predominant oligodendrocytic expression of Cx47 and display
      vacuolized myelin in the CNS.
AB  - To further characterize the recently described gap junction gene connexin 47
      (Cx47), we generated Cx47-null mice by replacing the Cx47 coding DNA with an
      enhanced green fluorescent protein (EGFP) reporter gene, which was thus placed
      under control of the endogenous Cx47 promoter. Homozygous mutant mice were
      fertile and showed no obvious morphological or behavioral abnormalities.
      Colocalization of EGFP fluorescence and immunofluorescence of cell marker
      proteins revealed that Cx47 was mainly expressed in oligodendrocytes in highly
      myelinated CNS tissues and in few calcium-binding protein S100beta subunit
      positive cells but not in neurons or peripheral sciatic nerve. This corrects our
      previous conclusion that Cx47 mRNA is expressed in brain and spinal cord neurons
      (Teubner et al., 2001). Cx47 protein was detected by Western blot analysis after
      immunoprecipitation in CNS tissues of wild-type mice but not in heart or Cx47
      deficient tissues. Electron microscopic analysis of CNS white matter in Cx47
      deficient mice revealed a conspicuous vacuolation of nerve fibers, particularly
      at the site of the optic nerve where axons are first contacted by
      oligodendrocytes and myelination starts. Initial analyses of Cx32/Cx47-double
      deficient mice showed that these mice developed an action tremor and died on
      average at 51 d after birth. The central white matter of these double-deficient
      mice exhibited much more abundant vacuolation in nerve fibers than mice deficient
      only in Cx47.

PMID- 12805294
TI  - Spontaneous oscillation by hair bundles of the bullfrog's sacculus.
AB  - One prominent manifestation of mechanical activity in hair cells is spontaneous
      otoacoustic emission, the unprovoked emanation of sound by an internal ear.
      Because active hair bundle motility probably constitutes the active process of
      nonmammalian hair cells, we investigated the ability of hair bundles in the
      bullfrog's sacculus to produce oscillations that might underlie spontaneous
      otoacoustic emissions. When maintained in the normal ionic milieu of the ear,
      many bundles oscillated spontaneously through distances as great as 80 nm at
      frequencies of 5-50 Hz. Whole-cell recording disclosed that the positive phase of
      movement was associated with the opening of transduction channels. Gentamicin,
      which blocks transduction channels, reversibly arrested oscillation; drugs that
      affect the cAMP phosphorylation pathway and might influence the activity of
      myosin altered the rate of oscillation. Increasing the Ca 2+ concentration
      rendered oscillations faster and smaller until they were suppressed; lowering the
      Ca 2+ concentration moderately with chelators had the opposite effect. When a
      bundle was offset with a stimulus fiber, oscillations were transiently suppressed
      but gradually resumed. Loading a bundle by partial displacement clamping, which
      simulated the presence of the accessory structures to which a bundle is
      ordinarily attached, increased the frequency and diminished the magnitude of
      oscillation. These observations accord with a model in which oscillations arise
      from the interplay of the hair bundle's negative stiffness with the activity of
      adaptation motors and with Ca 2+-dependent relaxation of gating springs.

PMID- 12805296
TI  - Amyloid precursor protein associates with a nicastrin-dependent docking site on
      the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence
      lifetime imaging.
AB  - Gamma-secretase cleavage is the final enzymatic step generating beta-amyloid via
      intramembranous cleavage of the amyloid precursor protein (APP). Presenilin (PS),
      initially identified as a gene in which mutations account for the vast majority
      of early-onset autosomal dominant Alzheimer's disease, is a major component of
      gamma-secretase. Enzymatic activity also depends on nicastrin, Aph-1, and Pen-2.
      We propose a model in which gamma-secretase components assemble, interact with
      substrates initially at a docking site, and then cleave and release substrates.
      To test this model, we developed a novel morphological technique on the basis of
      advanced fluorescence microscopy methods, fluorescence lifetime imaging
      microscopy (FLIM). FLIM allows us to examine protein-protein "proximity" in
      intact cells. We show that, although the strongest colocalization of APP and PS1
      is in the perinuclear area, the strongest interactions detected by FLIM are at or
      near the cell surface. We also found that APP-PS1 interactions occur even when
      gamma-secretase inhibitors or "dominant-negative" PS1 mutations are used to block
      gamma-secretase activity. Finally, using nicastrin RNA interference, we
      demonstrate that nicastrin is critical for APP association with PS1. We interpret
      these results to suggest that there is a noncatalytic docking site closely
      associated with PS1-gamma-secretase.

PMID- 12805297
TI  - Synapse-associated protein-97 isoform-specific regulation of surface AMPA
      receptors and synaptic function in cultured neurons.
AB  - Members of the synapse-associated protein-97 (SAP97) family of scaffold proteins
      have been implicated as central organizers of synaptic junctions to build
      macromolecular signaling complexes around specific postsynaptic neurotransmitter
      receptors. In this regard, SAP97 has been suggested to regulate the synaptic
      localization of glutamate receptor type 1 subunits of the AMPA-type glutamate
      receptors. To test this hypothesis directly, we assessed the effects of SAP97
      overexpression on surface expression of synaptic AMPA receptors. We find that
      recombinant SAP97 not only becomes concentrated at synaptic junctions but also
      leads to an increase in synaptic AMPA receptors, spine enlargement, and an
      increase in miniature EPSC (mEPSC) frequency, indicating that SAP97 has both
      postsynaptic and presynaptic effects on synaptic transmission. Synaptic targeting
      of SAP97, increased surface AMPA receptors, and increased mEPSC frequency are
      dependent on the presence of specific alternatively spliced sequences in SAP97
      that encode a protein 4.1 binding site. These results suggest that SAP97 can
      affect the synaptic recruitment of AMPA receptors and spine morphology and that
      these effects may be regulated by alternative splicing.

PMID- 12805298
TI  - The distribution of calcium buffering proteins in the turtle cochlea.
AB  - Hair cells of the inner ear contain high concentrations of calcium-binding
      proteins that limit calcium signals and prevent cross talk between different
      signaling pathways during auditory transduction. Using light microscope
      immunofluorescence and post-embedding immunogold labeling in the electron
      microscope, we characterized the distribution of three calcium-buffering proteins
      in the turtle cochlea. Both calbindin-D28k and parvalbumin-beta were confined to
      hair cells in which they showed a similar distribution, whereas calretinin was
      present mainly in hair-cell nuclei but also occurred in supporting cells and
      nerve fibers. The hair-cell concentration of calbindin-D28k but not of
      parvalbumin-beta increased from the low- to high-frequency end of the cochlea.
      Calibration against standards containing known amounts of calcium-buffering
      protein processed in the same fluid drop as the cochlear sections gave
      cytoplasmic concentrations of calbindin-D28k as 0.13-0.63 mm and parvalbumin-beta
      as approximately 0.25 mm, but calretinin was an order of magnitude less. Total
      amount of Ca 2+-binding sites on the proteins is at least 1.0 mm in low-frequency
      hair cells and 3.0 mm in high-frequency cells. Reverse transcription-PCR showed
      that mRNA for all three proteins was expressed in turtle hair cells. We suggest
      that calbindin-D28k and parvalbumin-beta may serve as endogenous mobile calcium
      buffers, but the predominantly nuclear location of calretinin argues for another
      role in calcium signaling. The results support conclusions from
      electrophysiological measurements that millimolar concentrations of endogenous
      calcium buffers are present in turtle hair cells. Parvalbumin-beta was also found
      in both inner and outer hair cells of the guinea pig cochlea.

PMID- 12805299
TI  - Regulated expression of ATF5 is required for the progression of neural progenitor
      cells to neurons.
AB  - An important milestone in brain development is the transition of neuroprogenitor
      cells to postmitotic neurons. We report that the bZIP transcription factor ATF5
      plays a major regulatory role in this process. In developing brain ATF5
      expression is high within ventricular zones containing neural stem and progenitor
      cells and is undetectable in postmitotic neurons. In attached clonal neurosphere
      cultures ATF5 is expressed by neural stem/progenitor cells and is undetectable in
      tau-positive neurons. In PC12 cell cultures nerve growth factor (NGF)
      dramatically downregulates endogenous ATF5 protein and transcripts, whereas
      exogenous ATF5 suppresses NGF-promoted neurite outgrowth. Such inhibition
      requires the repression of CRE sites. In contrast, loss of function conferred by
      dominant-negative ATF5 accelerates NGF-promoted neuritogenesis. Exogenous ATF5
      also suppresses, and dominant-negative ATF5 and a small-interfering RNA targeted
      to ATF5 promote, neurogenesis by cultured nestin-positive telencephalic cells.
      These findings indicate that ATF5 blocks the differentiation of neuroprogenitor
      cells into neurons and must be downregulated to permit this process to occur.

PMID- 12805300
TI  - The chemokine stromal cell-derived factor-1 promotes the survival of embryonic
      retinal ganglion cells.
AB  - The chemokine receptor CXCR4 is expressed in the embryonic and mature CNS, yet
      its normal physiological function in neurons remains obscure. Here, we show that
      its cognate chemokine, stromal cell-derived factor-1 (SDF-1), promotes the
      survival of cultured embryonic retinal ganglion cell neurons even in the absence
      of other neurotrophic factors. This survival effect is mediated primarily through
      a cAMP-dependent pathway that acts through protein kinase A and MAP kinase.
      Addition of SDF-1 to a human neuronal cell line induces phosphorylation of
      p44/p42 MAP kinase and GSK3beta. Mouse embryos lacking the CXCR4 receptor have a
      reduced number of retinal ganglion cells. The ligand of CXCR4, SDF-1, may
      therefore provide generalized trophic support to neurons during their development
      and maturation.

PMID- 12805301
TI  - Cell-autonomous mechanisms and myelin-associated factors contribute to the
      development of Purkinje axon intracortical plexus in the rat cerebellum.
AB  - The highly specific connection patterns of the mature CNS are shaped through
      finely regulated processes of axon growth and retraction. To investigate the
      relative contribution of cell-autonomous mechanisms and extrinsic cues in these
      events, we examined the development of Purkinje axon intracortical plexus in the
      rat cerebellum. During the first postnatal week, several new processes sprout
      from focal swellings along the initial portion of the Purkinje neurite and spread
      in the granular layer. Intense structural plasticity occurs during the following
      week, with pruning of collateral branches and remodeling of terminal arbors. The
      mature distribution of the Purkinje infraganglionic plexus, confined within the
      most superficial portion of the granular layer, is attained at approximately
      postnatal day 15. A similar neuritic branching pattern is also developed by
      Purkinje cells grown in cultures of dissociated cerebellar cells or transplanted
      to extracerebellar CNS regions, suggesting that cell-autonomous mechanisms
      contribute to determining the Purkinje axon phenotype. The structural remodeling
      of Purkinje intracortical plexus is concomitant with the development of
      cerebellar myelin. To ask whether myelin-associated factors contribute to the
      morphological maturation of Purkinje neurites, we prevented normal myelinogenesis
      by killing oligodendrocyte precursors with 5'-azacytidine or by applying
      neutralizing antibodies against the myelin-associated neurite growth inhibitor
      Nogo-A. In both conditions, Purkinje axons retained exuberant branches, and the
      terminal plexus spanned the entire extent of the granular layer. Thus, the
      formation of Purkinje axon collaterals is, in part, controlled by intrinsic
      determinants, but their growth and distribution are regulated by environmental
      signals, among which are myelin-derived cues.

PMID- 12805302
TI  - GABA receptors containing Rdl subunits mediate fast inhibitory synaptic
      transmission in Drosophila neurons.
AB  - GABAergic inhibition in Drosophila, as in other insects and mammals, is important
      for regulation of activity in the CNS. However, the functional properties of
      synaptic GABA receptors in Drosophila have not been described. Here, we report
      that spontaneous GABAergic postsynaptic currents (sPSCs) in cultured embryonic
      Drosophila neurons are mediated by picrotoxin-sensitive chloride-conducting
      receptors. A rapid increase in spontaneous firing in response to bath application
      of picrotoxin demonstrates that these GABA receptors mediate inhibition in the
      neuronal networks formed in culture. Many of the spontaneous GABAergic synaptic
      currents are sodium action potential independent [miniature IPSCs (mIPSCs)] but
      are regulated by external calcium levels. The large variation in mIPSC frequency,
      amplitude, and kinetics properties between neurons suggests heterogeneity in GABA
      receptor number, location, and/or subtype. A decrease in the mean mIPSC decay
      time constant between 2 and 5 d, in the absence of a correlated change in rise
      time, demonstrates that the functional properties of the synaptic GABA receptors
      are regulated during maturation in vitro. Finally, neurons from the GABA receptor
      subunit mutant Rdl exhibit reduced sensitivity to picrotoxin blockade of the
      mIPSCs and resistance to picrotoxin-induced increases in spontaneous firing
      frequency. This demonstrates that Rdl containing GABA receptors play a direct
      role in mediating synaptic inhibition in Drosophila neural circuits formed in
      culture.

PMID- 12805303
TI  - Inhibition of the proteasome by lactacystin enhances oligodendroglial cell
      differentiation.
AB  - We have used lactacystin, a specific inhibitor of the 26S proteasome, in
      oligodendroglial cell (OLGc) primary cultures to explore the possible
      participation of the proteasome-ubiquitin-dependent pathway in the decision of
      the OLGcs to arrest their proliferation and start differentiation. Addition of
      lactacystin at various concentrations to cultures containing a majority of OLGc
      was found to produce their withdrawal from the cell cycle and to induce their
      biochemical and morphological differentiation, with the appearance of extensive
      myelin-like sheets. The three classic proteolytic activities of the proteasome
      were significantly decreased in the lactacystin-treated cultures, and the
      immunocytochemical analysis showed an increase in the number of O4-, O1-, myelin
      basic protein-, and myelin proteolipid protein-positive cells and a decrease in
      A2B5-reacting cells. Quantitative immunochemical evaluation of the expression of
      certain proteins controlling the cell cycle showed an increase in p27kip1-,
      cyclin D-, and cdk4-positive cells, with a decrease in cyclin E- and cdk2
      positive cells. In the lactacystin-treated OLGcs, there was a dose-dependent
      decrease in the number of cells incorporating bromodeoxyuridine and in the
      activity of the complexes cyclin D-cdk4 and cyclin E-cdk2. Furthermore, increased
      levels of expression of several STAT factors were found, suggesting that
      proteasome inhibition in OLGcs could stabilize signals of survival and
      differentiation that might be processed through the JAK/STAT signaling cascade.

PMID- 12805304
TI  - The distribution of climbing and mossy fiber collateral branches from the copula
      pyramidis and the paramedian lobule: congruence of climbing fiber cortical zones
      and the pattern of zebrin banding within the rat cerebellum.
AB  - Individual cerebellar cortical zones defined by the somatotopy of climbing fiber
      responses and by their olivo-cortico-nuclear connections located in the
      paramedian lobule and the copula pyramidis of the rat cerebellum were
      microinjected with cholera toxin B subunit. Collateral branches of climbing and
      mossy fibers were mapped and related to the pattern of zebrin-positive and 
      negative bands of Purkinje cells. Climbing fiber collaterals from the copula
      distribute to the anterior lobe: from the paramedian lobule mainly to lobulus
      simplex and rostral crus I. Climbing fibers terminating in particular zones (X,
      A2, C1, CX, C2, C3, D1, and D2) in the paramedian lobule or the copula
      collateralize to one or two corresponding zones in lobulus simplex, crus I and
      II, the paraflocculus, and/or the anterior lobe. These zones can be defined by
      their relationship to the pattern of zebrin banding. Collaterals from mossy
      fibers, labeled from the same injection sites in the copula and paramedian
      lobule, often distribute bilaterally in a symmetrical pattern of multiple but ill
      defined longitudinal strips in the anterior lobe and/or lobulus simplex. One or
      more of these longitudinal aggregates of mossy fiber collaterals was always found
      subjacent to the strip(s) of labeled climbing fiber collaterals arising from the
      same locus in the paramedian lobule or the copula. Corticonuclear projections
      focused on the target nucleus of each zone, although a bilateral plexus of
      thinner axons, presumably of mossy fiber collateral origin, was sometimes also
      present in several other regions of the cerebellar nuclei. Overall, these results
      suggest that climbing fiber zones and zebrin banding reflect a common
      organizational scheme within the cerebellar cortex.

PMID- 12805305
TI  - Brainstem substrates of sympatho-motor circuitry identified using trans-synaptic
      tracing with pseudorabies virus recombinants.
AB  - Previous physiological investigations have suggested the existence of a neural
      circuit that coordinates activation of motor and autonomic efferents before or at
      the onset of exercise. Traditionally these circuits have been postulated to
      involve forebrain areas. However, overlapping populations of medullary reticular
      formation neurons that participate in motor or autonomic control have been
      described previously, suggesting that individual pontomedullary reticular
      formation neurons may coordinate both motor and autonomic responses. We tested
      this hypothesis by conducting transneuronal retrograde tracing of motor and
      sympathetic nervous system pathways in rats using recombinant strains of
      pseudorabies virus (PRV). A PRV strain expressing the green fluorescent protein
      (PRV-152) was injected into the left gastrocnemius muscle, which was surgically
      sympathectomized, whereas another recombinant (PRV-BaBlu) was injected into the
      left adrenal gland. Immunofluorescence methods using monospecific antisera and
      distinct fluorophores identified neurons infected with one or both of the
      recombinants. Brainstem neurons coinfected with both PRV recombinants, which
      presumably had collateralized projections to both adrenal sympathetic
      preganglionic neurons and gastrocnemius motoneurons, were observed in several
      areas of the pontomedullary reticular formation. The largest number of such
      neurons was located in the rostral ventromedial medulla within the ventral
      gigantocellular nucleus, gigantocellular nucleus pars alpha, raphe obscurus, and
      raphe magnus. These neurons are candidates for relaying central command signals
      to the spinal cord.

PMID- 12805306
TI  - Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors
      in sodium pump alpha2 subunit (Atp1a2)-deficient mice.
AB  - The sodium pump is the enzyme responsible for the maintenance of Na+ and K+
      gradients across the cell membrane. Four isoforms of the catalytic alpha subunit
      have been identified, but their individual roles remain essentially unknown. To
      investigate the necessary functions of the alpha2 subunit in vivo, we generated
      and analyzed mice defective in the alpha2 subunit gene. Mice homozygous for the
      alpha2 mutation died just after birth and displayed selective neuronal apoptosis
      in the amygdala and piriform cortex. In these regions, high expression of c-Fos
      before apoptosis indicated neural hyperactivity, and re-uptake of glutamic acid
      and GABA into P2 fraction containing crude synaptosome was impaired. These
      results indicate that the alpha2 subunit plays a critical role regulating neural
      activity in the developing amygdala and piriform cortex. Further supporting a
      role of the alpha2 subunit in the function of the amygdala, heterozygous adult
      mice showed augmented fear/anxiety behaviors and enhanced neuronal activity in
      the amygdala and piriform cortex after conditioned fear stimuli.

PMID- 12805307
TI  - Frequency-specific interaural level difference tuning predicts spatial response
      patterns of space-specific neurons in the barn owl inferior colliculus.
AB  - Space-specific neurons in the barn owl's inferior colliculus have spatial
      receptive fields (RFs) because of sensitivity to interaural time difference and
      frequency-specific interaural level difference (ILD). These neurons are assumed
      to be tuned to the frequency-specific ILDs occurring at their spatial RFs, but
      attempts to assess this tuning with traditional narrowband stimuli have had
      limited success. Indeed, tuning assessed in this manner, when processed via a
      linear model of spectral integration, typically explains only approximately half
      the variance in spatial response patterns. Here we report our findings that
      frequency-specific ILD tuning of space-specific neurons, when assessed from
      responses to broadband stimuli, predicted nearly 75% of the variance in spatial
      responses, using a linear model of spectral integration (p < 0.0001; n = 97
      neurons). Furthermore, when we tested neurons using only those frequencies we
      found to be spatially relevant, we saw that their responses were similar to those
      elicited by broadband stimuli. When we used frequencies not identified as
      spatially relevant, such similarity was lacking. Furthermore, spectral components
      that elicited high firing rates when presented as narrowband stimuli were found
      in several cases to be irrelevant for or detrimental to the definition of spatial
      RFs. Thus, neurons achieved sharp spatial tuning by selecting for ILDs of a
      subset of spectral components in noise, some of which were not identified using
      narrowband stimuli.

PMID- 12805308
TI  - Functional organization of human intraparietal and frontal cortex for attending,
      looking, and pointing.
AB  - We studied the functional organization of human posterior parietal and frontal
      cortex using functional magnetic resonance imaging (fMRI) to map preparatory
      signals for attending, looking, and pointing to a peripheral visual location. The
      human frontal eye field and two separate regions in the intraparietal sulcus were
      similarly recruited in all conditions, suggesting an attentional role that
      generalizes across response effectors. However, the preparation of a pointing
      movement selectively activated a different group of regions, suggesting a
      stronger role in motor planning. These regions were lateralized to the left
      hemisphere, activated by preparation of movements of either hand, and included
      the inferior and superior parietal lobule, precuneus, and posterior superior
      temporal sulcus, plus the dorsal premotor and anterior cingulate cortex
      anteriorly. Surface-based registration of macaque cortical areas onto the map of
      fMRI responses suggests a relatively good spatial correspondence between human
      and macaque parietal areas. In contrast, large interspecies differences were
      noted in the topography of frontal areas.

PMID- 12805309
TI  - Deformation of network connectivity in the inferior olive of connexin 36
      deficient mice is compensated by morphological and electrophysiological changes
      at the single neuron level.
AB  - Compensatory mechanisms after genetic manipulations have been documented
      extensively for the nervous system. In many cases, these mechanisms involve
      genetic regulation at the transcription or expression level of existing isoforms.
      We report a novel mechanism by which single neurons compensate for changes in
      network connectivity by retuning their intrinsic electrical properties. We
      demonstrate this mechanism in the inferior olive, in which widespread electrical
      coupling is mediated by abundant gap junctions formed by connexin 36 (Cx36). It
      has been shown in various mammals that this electrical coupling supports the
      generation of subthreshold oscillations, but recent work revealed that rhythmic
      activity is sustained in knock-outs of Cx36. Thus, these results raise the
      question of whether the olivary oscillations in Cx36 knock-outs simply reflect
      the status of wild-type neurons without gap junctions or the outcome of
      compensatory mechanisms. Here, we demonstrate that the absence of Cx36 results in
      thicker dendrites with gap-junction-like structures with an abnormally wide
      interneuronal gap that prevents electrotonic coupling. The mutant olivary neurons
      show unusual voltage-dependent oscillations and an increased excitability that is
      attributable to a combined decrease in leak conductance and an increase in
      voltage-dependent calcium conductance. Using dynamic-clamp techniques, we
      demonstrated that these changes are sufficient to transform a wild-type neuron
      into a knock-out-like neuron. We conclude that the absence of Cx36 in the
      inferior olive is not compensated by the formation of other gap-junction channels
      but instead by changes in the cytological and electroresponsive properties of its
      neurons, such that the capability to produce rhythmic activity is maintained.

PMID- 12805310
TI  - Evidence for enhanced neurobehavioral vulnerability to nicotine during
      periadolescence in rats.
AB  - Epidemiological studies indicate that there is an increased likelihood for the
      development of nicotine addiction when cigarette smoking starts early during
      adolescence. These observations suggest that adolescence could be a "critical"
      ontogenetic period, during which drugs of abuse have distinct effects responsible
      for the development of dependence later in life. We compared the long-term
      behavioral and molecular effects of repeated nicotine treatment during either
      periadolescence or postadolescence in rats. It was found that exposure to
      nicotine during periadolescence, but not a similar exposure in the postadolescent
      period, increased the intravenous self-administration of nicotine and the
      expression of distinct subunits of the ligand-gated acetylcholine receptor in
      adult animals. Both these changes indicated an increased sensitivity to the
      addictive properties of nicotine. In conclusion, adolescence seems to be a
      critical developmental period, characterized by enhanced neurobehavioral
      vulnerability to nicotine.

PMID- 12805311
TI  - Corollary discharge inhibition of ascending auditory neurons in the stridulating
      cricket.
AB  - Acoustically communicating animals are able to process external acoustic stimuli
      despite generating intense sounds during vocalization. We have examined how the
      crickets' ascending auditory pathway copes with self-generated, intense auditory
      signals (chirps) during singing (stridulation). We made intracellular recordings
      from two identified ascending auditory interneurons, ascending neuron 1 (AN1) and
      ascending neuron 2 (AN2), during pharmacologically elicited sonorous (two
      winged), silent (one-winged), and fictive (isolated CNS) stridulation. During
      sonorous chirps, AN1 responded with bursts of spikes, whereas AN2 was inhibited
      and rarely spiked. Low-amplitude hyperpolarizing potentials were recorded in AN1
      and AN2 during silent chirps. The potentials were also present during fictive
      chirps. Therefore, they were the result of a centrally generated corollary
      discharge from the stridulatory motor network. The spiking response of AN1 and
      AN2 to acoustic stimuli was inhibited during silent and fictive chirps. The
      maximum period of inhibition occurred in phase with the maximum spiking response
      to self-generated sound in a sonorously stridulating cricket. In some experiments
      (30%) depolarizing potentials were recorded during silent chirps. Reafferent
      feedback elicited by wing movement was probably responsible for the depolarizing
      potentials. In addition, two other sources of inhibition were present in AN1: (1)
      IPSPs were elicited by stimulation with 12.5 kHz stimuli and (2) a long-lasting
      hyperpolarization followed spiking responses to 4.5 kHz stimuli. The
      hyperpolarization desensitized the response of AN1 to subsequent quieter stimuli.
      Therefore, the corollary discharge will reduce desensitization by suppressing the
      response of AN1 to self-generated sounds.

PMID- 12805312
TI  - Human theta oscillations related to sensorimotor integration and spatial
      learning.
AB  - oscillations in the rat hippocampus have been implicated in sensorimotor
      integration (Bland, 1986), especially during exploratory and wayfinding behavior.
      We propose that human cortical activity coordinates sensory information with a
      motor plan to guide wayfinding behavior to known goal locations. To test this
      hypothesis, we analyzed invasive recordings from epileptic patients while they
      performed a spatially immersive, virtual taxi driver task. Consistent with this
      hypothesis, we found oscillations during both exploratory search and goal-seeking
      behavior and, in particular, during virtual movement, when sensory information
      and motor planning were both in flux, compared with periods of self-initiated
      stillness. oscillations had different topographic and spectral characteristics
      during searching than during goal-seeking, suggesting that different cortical
      networks exhibit depending on which cognitive functions are driving behavior
      (spatial learning during exploration vs orienting to a learned representation
      during goal-seeking). In contrast, oscillations in the beta band appeared to be
      related to simple motor planning, likely a variant of the Rolandic mu rhythm.
      These findings suggest that human cortical oscillations act to coordinate sensory
      and motor brain activity in various brain regions to facilitate exploratory
      learning and navigational planning.

PMID- 12805314
TI  - The receptive-field organization of simple cells in primary visual cortex of
      ferrets under natural scene stimulation.
AB  - The responses of simple cells in primary visual cortex to sinusoidal gratings can
      primarily be predicted from their spatial receptive fields, as mapped using spots
      or bars. Although this quasilinearity is well documented, it is not clear whether
      it holds for complex natural stimuli. We recorded from simple cells in the
      primary visual cortex of anesthetized ferrets while stimulating with flashed
      digitized photographs of natural scenes. We applied standard reverse-correlation
      methods to quantify the average natural stimulus that invokes a neuronal
      response. Although these maps cannot be the receptive fields, we find that they
      still predict the preferred orientation of grating for each cell very well (r =
      0.91); they do not predict the spatial-frequency tuning. Using a novel
      application of the linear reconstruction method called regularized pseudoinverse,
      we were able to recover high-resolution receptive-field maps from the responses
      to a relatively small number of natural scenes. These receptive-field maps not
      only predict the optimum orientation of each cell (r = 0.96) but also the spatial
      frequency optimum (r = 0.89); the maps also predict the tuning bandwidths of many
      cells. Therefore, our first conclusion is that the tuning preferences of the
      cells are primarily linear and constant across stimulus type. However, when we
      used these maps to predict the actual responses of the cells to natural scenes,
      we did find evidence of expansive output nonlinearity and nonlinear influences
      from outside the classical receptive fields, orientation tuning, and spatial
      frequency tuning.

PMID- 12805313
TI  - Transient receptor potential channel activation causes a novel form of [Ca 2+]I
      oscillations and is not involved in capacitative Ca 2+ entry in glial cells.
AB  - Astrocytes express transient receptor potential channels (TRPCs), which have been
      implicated in Ca 2+ influx triggered by intracellular Ca 2+ stores depletion, a
      phenomenon known as capacitative Ca 2+ entry. We studied the properties of
      capacitative Ca 2+ entry in astrocytes by means of single-cell Ca 2+ imaging with
      the aim of understanding the involvement of TRPCs in this function. We found
      that, in astrocytes, capacitative Ca 2+ entry is not attributable to TRPC opening
      because the TRPC-permeable ions Sr2+ and Ba2+ do not enter astrocytes during
      capacitative Ca 2+ entry. Instead, natively expressed oleyl-acetyl-glycerol (OAG)
      (a structural analog of DAG) -sensitive TRPCs, when activated, initiate
      oscillations of cytosolic Ca 2+ concentration ([Ca 2+]i) pharmacologically and
      molecularly consistent with TRPC3 activation. OAG-induced [Ca 2+]i oscillations
      are not affected by inhibition of inositol trisphosphate (InsP3) production or
      blockade of the InsP3 receptor, therefore representing a novel form of [Ca 2+]i
      signaling. Instead, high [Ca 2+]i inhibited oscillations, by closing the OAG
      sensitive channel. Also, treatment of astrocytes with antisense against TRPC3
      caused a consistent decrease of the cells responding to OAG. Exogenous OAG but
      not endogenous DAG seems to activate TRPC3. In conclusion, in glial cells,
      natively expressed TRPC3s mediates a novel form of Ca 2+ signaling, distinct from
      capacitative Ca 2+ entry, which suggests a specific signaling function for this
      channel in glial cells.

PMID- 12805315
TI  - Early odor preference learning in the rat: bidirectional effects of cAMP response
      element-binding protein (CREB) and mutant CREB support a causal role for
      phosphorylated CREB.
AB  - Early odor preference learning in rats is associated with increases of
      phosphorylated CREB (pCREB) in mitral cells of the olfactory bulb. In the present
      study, herpes simplex virus expressing CREB (HSV-CREB) and dominant-negative
      mutant CREB (HSV-mCREB) have been injected into the bulb to assess a causal role
      for CREB and pCREB in this model. Odor paired with stroking or with the beta
      adrenoceptor agonist isoproterenol produces odor approach 24 hr later.
      Isoproterenol-induced learning exhibits an inverted U curve dose-dependent
      learning relationship with both low and high doses failing to produce learning.
      pCREB increases have only been seen at the learning effective dose. In the
      present study, injection of an HSV vector expressing mutant CREB into the
      olfactory bulb prevented learning induced by stroking. Control HSV expressing
      LacZ was without effect. Expression of mutant CREB shifted the dose-learning
      curve for isoproterenol to the right such that a higher dose was required to
      induce learning. Expression of CREB shifted the dose-learning curve for
      isoproterenol to the left, with a lower dose now producing learning. As expected
      from this shift, CREB overexpression interfered with learning induced by
      stroking. When learning occurred, with either CREB or mutant CREB, pCREB was
      observed to be elevated relative to the nonlearning LacZ control groups.
      Unexpectedly, with odor plus stroking in the nonlearning CREB group, the level of
      pCREB was also higher than with odor plus stroking in LacZ controls that did
      learn. The data demonstrate a causal role for CREB and pCREB in early mammalian
      odor preference learning, reinforcing CREB as a "universal" memory molecule. They
      support evidence that CREB overexpression can be deleterious and suggest the
      hypothesis of an optimal pCREB window for learning.

PMID- 12805316
TI  - Fatigue and paradoxical enhancement of heat response in C-fiber nociceptors from
      cross-modal excitation.
AB  - Fatigue refers to the decrement of response seen with repeated stimulation and is
      a prominent attribute of nociceptors. Whether fatigue in nociceptors involves
      transduction, spike initiation, or conduction mechanisms is unknown. We
      investigated systematically how electrical, mechanical, and heat conditioning
      stimuli (eCS, mCS, hCS) affected the subsequent response to a test-heat stimulus
      applied 5 sec later to the receptive field of cutaneous nociceptors. Standard
      teased-fiber techniques were used to record from mechano-heat-sensitive C-fiber
      afferents in the anesthetized monkey. The eCS was applied to the nerve trunk,
      whereas the hCS and mCS were applied to the heat-test site. For the eCS, the
      number of pulses rather than frequency of stimulation determined the level of
      fatigue. Fatigue varied inversely with the time interval between the eCS and the
      test stimulus. For comparable responses from the CS, the magnitude of fatigue was
      less after the mCS than after the eCS. The mCS (but not the eCS) sometimes evoked
      a paradoxical increase in response to the test-heat stimulus. Recovery from
      fatigue was significantly faster after the eCS and mCS than the hCS. The
      paradoxical enhancement after the mCS probably results from temporal summation of
      generator potentials produced by mechanical and heat stimulation and suggests
      that the time constant of the generator potential is on the order of seconds.
      Concurrent enhancement-fatigue effects may also explain why fatigue was less
      after the mCS than the eCS. The dependency of recovery from fatigue on the
      modality of the CS suggests that fatigue results from transduction-spike
      initiation mechanisms.

PMID- 12805317
TI  - Morphine withdrawal increases glutamate uptake and surface expression of
      glutamate transporter GLT1 at hippocampal synapses.
AB  - Opiate abuse causes adaptive changes in several processes of synaptic
      transmission in which the glutamatergic system appears a critical element
      involved in opiate tolerance and dependence, but the underlying mechanisms remain
      unclear. In the present study, we found that glutamate uptake in hippocampal
      synaptosomes was significantly increased (by 70% in chronic morphine-treated
      rats) during the morphine withdrawal period, likely attributable to an increase
      in the number of functional glutamate transporters. Immunoblot analysis showed
      that expression of GLT1 (glutamate transporter subtype 1) was identified to be
      upregulated in synaptosomes but not in total tissues, suggesting a redistribution
      of glutamate transporter expression. Moreover, the increase in glutamate uptake
      was reproduced in cultured neurons during morphine withdrawal, and the increase
      of uptake in neurons could be blocked by dihydrokainate, a specific inhibitor of
      GLT1. Cell surface biotinylation and immunoblot analysis showed that morphine
      withdrawal produced an increase in GLT1 expression rather than EAAC1 (excitatory
      amino acids carrier 1), a neuronal subtype, at the cultured neuronal cell
      surface, whereas no significant change was observed in that of cultured
      astrocytes. Electron microscopy also revealed that GLT1 expression was markedly
      increased in the nerve terminals of hippocampus and associated with the plasma
      membrane in vivo. These results suggest that GLT1 in hippocampal neurons can be
      induced to translocate to the nerve terminals and express on the cell surface
      during morphine withdrawal. The translocation of GLT1 at synapses during morphine
      withdrawal provides a neuronal mechanism for modulation of excitatory
      neurotransmission during opiate abuse.

PMID- 12805318
TI  - The glucocorticoid receptor as a potential target to reduce cocaine abuse.
AB  - Several findings suggest that glucocorticoid hormones are involved in determining
      the propensity of an individual to develop cocaine abuse. These hormones activate
      two related transcription factors, the glucocorticoid receptor (GR) and the
      mineralocorticoid receptor. In this study, we show that the selective
      inactivation of the GR gene in the brains of mice profoundly flattened the dose
      response function for cocaine intravenous self-administration and suppressed
      sensitization, two experimental procedures considered relevant models of
      addiction. Furthermore, administration of a GR antagonist dose-dependently
      reduced the motivation to self-administer cocaine. Importantly, the absence of GR
      did not modify the basal behavioral and molecular effects of cocaine but
      selectively modified the excessive response to the drug spontaneously present in
      certain vulnerable individuals or induced by repeated drug exposure in others. In
      conclusion, we provide the first genetic evidence that the GR gene can modulate
      cocaine abuse. This suggests that targeting GR function in the brain could
      provide new therapeutic strategies to treat cocaine addiction for which there is
      no available treatment.

PMID- 12805319
TI  - Gene therapy: the challenges of translating laboratory research into clinical
      practice.

PMID- 12805320
TI  - The surveillance, epidemiology, and end-results program database as a resource
      for conducting descriptive epidemiologic and clinical studies.

PMID- 12805321
TI  - The gastric cancer treatment controversy.

PMID- 12805322
TI  - Repeated intravesical instillations of an adenoviral vector in patients with
      locally advanced bladder cancer: a phase I study of p53 gene therapy.
AB  - PURPOSE: We investigated the feasibility, safety, and biologic activity of
      adenovirus-mediated p53 gene transfer in patients with locally advanced bladder
      cancer. PATIENTS AND METHODS: Patients with measurable, locally advanced
      transitional-cell carcinoma of the bladder who were not candidates for cystectomy
      were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV
      p53) were administered on days 1 and 4 at three dose levels (10(10) particles to
      10(12) particles) or on either 4 or 8 consecutive days at a single dose level
      (10(12) particles). RESULTS: Thirteen patients received a total of 22 courses
      without dose-limiting toxicity. Specific transgene expression was detected by
      reverse transcriptase polymerase chain reaction in bladder biopsy tissue from two
      of seven assessable patients. There were no changes in p53, p21waf1/cip1, or bax
      protein levels in bladder epithelium evident from immunohistochemical analysis of
      11 assessable patients. Outpatient administration of multiple courses was
      feasible and well tolerated. A patient with advanced superficial bladder cancer
      showed evidence of tumor response. CONCLUSION: Intravesical instillation of
      Ad5CMV-p53 is safe, feasible, and biologically active when administered in
      multiple doses to patients with bladder cancer. Observations from this study
      indicate that this treatment has an antitumor effect in superficial transitional
      cell carcinoma. Improvements in the efficiency of gene transfer and the levels of
      gene expression are required to develop more effective gene therapy for bladder
      cancer.

PMID- 12805323
TI  - Inflammatory breast carcinoma and noninflammatory locally advanced breast
      carcinoma: distinct clinicopathologic entities?
AB  - PURPOSE: Inflammatory breast carcinoma (IBC) and noninflammatory locally advanced
      breast carcinoma (LABC) are both associated with poor prognosis; however, whether
      they are distinct clinicopathologic entities remains controversial. MATERIALS AND
      METHODS: To determine whether IBC and LABC were different, we compared tumor
      characteristics, prognosis, and age-specific incidence rate patterns in the
      Surveillance, Epidemiology, and End-Results program. An age of 50 years served as
      a surrogate marker for menopause. RESULTS: Younger age at diagnosis, poorer tumor
      grade, and negative estrogen receptors (ERs) were more predictive of IBC (n =
      2,237) than of LABC (n = 7,985). Breast carcinoma survival was worse for patients
      with IBC than for those with LABC (log-rank test, P <.0001). Age-specific
      incidence rates for IBC increased until 50 years and then flattened, whereas
      rates for LABC increased for all ages. When rates for LABC were stratified by
      estrogen receptor-positive (ERP) and -negative (ERN) expression, rates for ERP
      and ERN diverged; that is, rates for ERP increased with advancing age, whereas
      rates for ERN flattened after 50 years. When rates for IBC were stratified by ER
      expression, rates for both ERP and ERN flattened after 50 years of age.
      CONCLUSION: IBC and LABC seemed to be distinct biologic entities, as indicated by
      different prognostic factor profiles and age-specific incidence rate patterns.
      Rates that increased before 50 years and then stabilized, possibly indicated that
      premenopausal exposures had a greater effect on maintaining rates for IBC than
      for LABC.

PMID- 12805324
TI  - Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving
      surgery in postmenopausal women with stage I breast cancer: a decision analysis.
AB  - PURPOSE: To compare outcomes for hypothetical cohorts of postmenopausal patients
      with estrogen receptor-positive tumors that are < or = 2 cm in size, with
      pathologically uninvolved axillary nodes, treated with radiation therapy plus
      tamoxifen versus tamoxifen alone after breast-conserving surgery. METHODS: A
      Markov model was used to simulate patients' clinical course and estimate overall
      survival, recurrence-free survival, time with an intact breast, and death from
      breast cancer. Probabilities were derived from randomized trials and
      retrospective studies. Analyses were performed separately by age of diagnosis in
      5-year increments from 50 to 80 years. Sensitivity analyses tested the stability
      of radiation benefit. RESULTS: The modeled recurrence-free survival benefit of
      giving radiation therapy was 3.35 years for women who were 50 years of age at
      diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year
      old cohort, radiation therapy resulted in additional 0.60 years survival,
      compared with 0.04 years among 80-year-olds. A 50-year-old woman who received
      radiation therapy plus tamoxifen was less likely to die from breast cancer than
      if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An
      80-year-old woman had a 1.17% chance of dying from breast cancer if she received
      radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative
      risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit
      was strongly influenced by including unequal rates of developing distant disease
      after breast recurrence between the treatment arms and varying rates of local
      recurrence. CONCLUSION: The absolute and relative benefits of radiation therapy
      and individual patient preferences for different health states should be
      considered when selecting treatment.

PMID- 12805325
TI  - Barriers to clinical trial participation by older women with breast cancer.
AB  - PURPOSE: Although 48% of breast cancer patients are 65 years old or older, these
      older patients are severely underrepresented in breast cancer clinical trials.
      This study tested whether older patients were offered trials significantly less
      often than younger patients and whether older patients who were offered trials
      were more likely to refuse participation than younger patients. PATIENTS AND
      METHODS: In 10 Cancer and Leukemia Group B institutions, using a retrospective
      case-control design, breast cancer patients eligible for an open treatment trial
      were paired: less than 65 years old and > or = 65 years old. Each of the 77 pairs
      were matched by disease stage and treating physician. Patients were interviewed
      as to their reasons for participating or refusing to participate in a trial. The
      treating physicians were also given questionnaires about their reasons for
      offering or not offering a trial. RESULTS: Sixty-eight percent of younger stage
      II patients were offered a trial compared with 34% of the older patients (P
      =.0004). In multivariate analyses, disease stage and age remained highly
      significant in predicting trial offering (P =.0008), when controlling for
      physical functioning and comorbidity. Of those offered a trial, there was no
      significant difference in participation between younger (56%) and older (50%)
      patients (P =.67). CONCLUSION: In a multivariate analysis including comorbid
      conditions, age and stage were the only predictors of whether a patient was
      offered a trial. The greatest impediment to enrolling older women onto trials in
      the setting of this study was the physicians' perceptions about age and tolerance
      of toxicity.

PMID- 12805326
TI  - Randomized trial of 2 versus 5 years of adjuvant tamoxifen for women aged 50
      years or older with early breast cancer: Italian Interdisciplinary Group Cancer
      Evaluation Study of Adjuvant Treatment in Breast Cancer 01.
AB  - PURPOSE: To compare 2 with 5 years of adjuvant tamoxifen therapy in the treatment
      of early breast cancer. PATIENTS AND METHODS: Women with breast carcinoma T1-3,
      N0-3, M0, who were between 50 and 70 years of age, were eligible irrespective of
      menopausal status, tumor grade, or estrogen receptor (ER) status. Patients who
      were event-free after 2 years of tamoxifen therapy were randomly assigned to stop
      or continue tamoxifen therapy for an additional 3 years. The primary end point
      was length of disease-free survival (DFS). Secondary end points included overall
      survival (OS) and toxicity. RESULTS: From 1989 through 1996, 1,901 patients were
      randomly assigned either to stop treatment (n = 958) or to receive tamoxifen for
      3 additional years (n = 943). The median duration of postrandomization follow-up
      was 52 months. We found no statistically significant differences between the 5
      year arm and the 2-year arm in terms of DFS (hazard ratio [HR], 0.91; 95%
      confidence interval [CI], 0.76 to 1.08) and OS (HR, 1.16; 95% CI, 0.92 to 1.46).
      In ER-positive patients, a statistically significant prolongation of DFS related
      to longer treatment duration was observed (HR, 0.74; 95% CI, 0.59 to 0.93),
      whereas no difference in OS could be detected (HR, 0.98; 95% CI, 0.72 to 1.32).
      No differences in terms of endometrial cancers, cardiac or cerebrovascular
      events, or fractures were detected, whereas a doubling in the risk of
      thromboembolic events was found in the 5-year arm. CONCLUSION: Our results
      confirm previous research that shows that 5 years of tamoxifen decreases
      recurrence compared to 2 years in patients with ER-positive tumors.

PMID- 12805327
TI  - Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and
      Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric
      cancer: Japan Clinical Oncology Group 9206-1.
AB  - PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative
      resection in serosa-negative gastric cancer patients (excluding patients who were
      T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer
      centers in Japan participated. PATIENTS AND METHODS: From January 1993 to
      December 1994, 252 patients were enrolled into the study and allocated randomly
      to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous
      mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2
      twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for
      the next 18 months for a total dose of 67 g/m2. The primary end point was relapse
      free survival. Overall survival and the site of recurrence were secondary end
      points. RESULTS: Ninety-eight percent of patients underwent gastrectomy with D2
      or greater lymph node dissection. There were no treatment-related deaths and few
      serious adverse events. There was no significant difference in relapse-free and
      overall survival between the arms (5-year relapse-free survival 88.8%
      chemotherapy v 83.7% surgery alone; P =.14 and 5-year survival 91.2% chemotherapy
      v 86.1% surgery alone; P =.13, respectively). Nine patients (7.1%) in the
      chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer
      recurrence. CONCLUSION: There was no statistically significant relapse-free or
      overall survival benefit with this adjuvant chemotherapy for patients with
      macroscopically serosa-negative gastric cancer after curative resection, and
      there was no statistical difference between the two arms relating to the types of
      cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen
      for this population in clinical practice.

PMID- 12805328
TI  - Soluble E-cadherin is an independent pretherapeutic factor for long-term survival
      in gastric cancer.
AB  - PURPOSE: To evaluate whether pretherapeutic serum soluble E-cadherin is an
      independent factor predicting long-term survival in gastric cancer. Gastric
      cancer remains the second leading cause of cancer-related deaths in the world,
      but a satisfactory tumor marker is currently unavailable for gastric cancer.
      Soluble E-cadherin has recently been found to have prognostic value in gastric
      cancer. PATIENTS AND METHODS: One hundred sixteen patients with histologically
      proven gastric adenocarcinoma were included in the trial. Pretherapeutic serum
      was collected, and soluble E-cadherin was assayed using a commercially available
      enzyme-linked immunosorbent assay kit. The patients were followed up
      prospectively at the outpatient clinic. RESULTS: There were 75 men and 41 women,
      with a mean (+/- SD) age of 66 +/- 14 years. Forty-eight percent of tumors were
      located in the gastric antrum. The median survival time was 11 months. The mean
      pretherapeutic value of soluble E-cadherin was 9,159 ng/mL (range, 6,002 to
      10,025 ng/mL), and the mean pretherapeutic level of carcinoembryonic antigen was
      11 ng/mL (range, 0.3 to 4,895 ng/mL). On multivariate analysis, soluble E
      cadherin is an independent factor predicting long-term survival. Ninety percent
      of patients with a serum level of E-cadherin greater than 10,000 ng/mL had a
      survival time of less than 3 years (P =.009). CONCLUSION: Soluble E-cadherin is a
      potentially valuable pretherapeutic prognostic factor in patients with gastric
      cancer.

PMID- 12805329
TI  - Simple clinical prognostic model for hepatocellular carcinoma in developing
      countries and its validation.
AB  - PURPOSE: More than 80% of hepatocellular carcinomas (HCCs) worldwide occur in
      developing countries, especially in Asia. It often presents at an advanced stage
      beyond treatment. In this circumstance, a simple prognostic model is useful.
      Previous prognostic models require radiologic and laboratory investigations that
      are not readily available in developing countries. Our aim is to formulate and
      then validate a simple clinical prognostic model for HCC in an Asian population
      using only clinical parameters and with serum alpha-fetoprotein (AFP) as the sole
      laboratory test. PATIENTS AND METHODS: Cox regression modeling was performed on
      several clinical parameters and serum AFP level in 397 patients with HCC who
      received only supportive care in Singapore. A later group of 324 HCC patients
      from an Asia-Pacific-wide randomized trial was then used to validate the model.
      RESULTS: Ascites, physical performance status, and serum AFP were independently
      predictive of survival. Cox analysis yielded a simple score based on these three
      variables that categorizes patients into low-, medium-, and high-risk groups with
      6-month survivals of 43%, 21%, and 5%, respectively. The prospective validation
      data provided corresponding estimates of 33%, 15%, and 3% and give confirmation
      of the utility of the simple model. CONCLUSION: We have formulated and
      prospectively validated a simple prognostic score for untreated HCC that only
      requires a clinical evaluation for ascites and physical performance status and
      measurement of serum AFP. This simple model is particularly apt for developing
      country circumstances and can also be used to select patients for treatment
      trials.

PMID- 12805330
TI  - Phase II trial of thalidomide and carmustine for patients with recurrent high
      grade gliomas.
AB  - PURPOSE: The use of thalidomide as an antiangiogenic agent has met with only
      limited success in the treatment of malignant gliomas. On the basis of
      preclinical data demonstrating synergistic antitumor activity when antiangiogenic
      agents are combined with cytotoxic agents, we explored the clinical activity of
      the combination of thalidomide and carmustine (BCNU) in patients with recurrent
      high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of
      high-grade glioma and radiographic evidence of tumor progression after standard
      surgery, radiation, and chemotherapy were eligible for the study. Patients
      received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of
      thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated.
      RESULTS: A total of 40 patients (38 with glioblastomas, two with anaplastic
      gliomas) were accrued to the study. The combination of thalidomide and BCNU was
      well tolerated; mild myelosuppression and mild to moderate sedation were the most
      common side effects. The median progression-free survival (100 days) and the
      objective radiographic response rate (24%) for patients with glioblastoma
      compared favorably with data from historical controls. CONCLUSION: This is one of
      the first clinical trials to evaluate the strategy of combining a putative
      antiangiogenic agent with a cytotoxic agent in patients with primary brain
      tumors. Our data demonstrate that thalidomide in combination with BCNU is well
      tolerated and has antitumor activity in patients with recurrent high-grade
      gliomas. Although the combination seems to be more active than either agent
      alone, such conclusions await confirmatory trials.

PMID- 12805331
TI  - Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of
      recurrent and progressive malignant glioma: a North American Brain Tumor
      Consortium study.
AB  - PURPOSE: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in
      prior single-agent trials of recurrent malignant gliomas (MG). This phase II
      trial evaluated efficacy and toxicity of combination temozolomide and cRA
      treatment in recurrent MG. PATIENTS AND METHODS: Adults with recurrent
      supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were
      eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and
      cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression
      free survival at 6 months (PFS 6); secondary end points included response,
      survival, and PFS12. RESULTS: Eighty-eight eligible patients (glioblastoma
      multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28;
      oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95%
      confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%).
      Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall
      survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to
      57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable
      patients, there were two (3%) complete responses and eight (12%) partial
      responses (complete plus partial response, 15%). Among 499 treatment cycles, the
      most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia
      (1.4%), and hypertriglyceridemia (1.2%). CONCLUSION: TMZ and cRA were active,
      exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our
      previously reported database (glioblastoma multiforme: expected, 30%; observed,
      32%; anaplastic glioma: expected, 40%; observed, 50%).

PMID- 12805332
TI  - Single nucleotide polymorphism of the human kallikrein-2 gene highly correlates
      with serum human kallikrein-2 levels and in combination enhances prostate cancer
      detection.
AB  - PURPOSE: We examined the relationship between a mutant (T) for wild-type (C)
      allele substitution of the human kallikrein-2 gene (KLK2), circulating human
      kallikrein-2 (hK2) levels and prostate cancer risk. PATIENTS AND METHODS: We
      studied 1,287 consecutive men who underwent prostate biopsies because of an
      abnormal prostate-specific antigen level. Serum and DNA were obtained before
      biopsy. Cases were patients with cancer, and controls were patients with no
      cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the
      T and C alleles, respectively. RESULTS: Of the 1,287 men, 616 had cancer, and 671
      had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was
      55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC,
      CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the
      genotypes, respectively (P =.0001). The adjusted odds ratios for prostate cancer
      for patients with the TT and CT genotypes compared with patients with the CC
      genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P =.004) and 1.51
      (95% CI, 1.2 to 2.0; P =.002), respectively. The adjusted odds ratio for prostate
      cancer for patients in the fourth quartile of hK2 compared with the first
      quartile was 4.33 (95% CI, 2.9 to 6.4; P =.0001). When combined, the adjusted
      odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P =.0001)
      for patients with high hK2 levels and at least one T allele. CONCLUSION: The C/T
      polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and,
      in combination, are highly predictive for prostate cancer.

PMID- 12805333
TI  - High-dose therapy and autologous stem-cell transplantation versus conventional
      therapy for patients with advanced Hodgkin's lymphoma responding to front-line
      therapy.
AB  - PURPOSE: To determine whether high-dose therapy (HDT) with autologous stem-cell
      transplantation (ASCT) should be included in the initial consolidative treatment
      of patients with advanced, unfavorable Hodgkin's lymphoma (HL). PATIENTS AND
      METHODS: One hundred sixty-three patients achieving complete remission (CR) or
      partial remission (PR) with four initial courses of doxorubicin, bleomycin,
      vinblastine, and dacarbazine, or other doxorubicin-containing regimens, were
      randomly assigned to receive HDT plus ASCT (83 patients) versus four courses of
      conventional chemotherapy (80 patients). Unfavorable HL was defined as the
      presence of at least two of the following poor prognostic factors: high lactate
      dehydrogenase level, large mediastinal mass (greater than at least 33% of the
      thoracic diameter), more than one extranodal site, low hematocrit level, and
      inguinal involvement. RESULTS: At the end of the treatment program, 92% of
      patients in arm A and 89% in arm B achieved a CR (P =.6). After a median follow
      up of 48 months, the 5-year failure-free survival rates were 75% (95% confidence
      interval [CI], 65 to 85) in arm A and 82% (95% CI, 73 to 90) in arm B (P =.4).
      The 5-year overall survival rates were 88% (95% CI, 80 to 96) in arm A and 88%
      (95% CI, 79 to 96) in arm B (P =.99). The 5-year relapse-free survival rates were
      88% in arm A (95% CI, 80 to 96) and 94% in arm B (95% CI, 88 to 100), and the
      difference was not significant (P =.3). CONCLUSION: Patients with advanced
      unfavorable HL achieving CR or PR after four courses of doxorubicin-containing
      regimens have a favorable outcome with conventional chemotherapy. No benefit from
      an early intensification with HDT and ASCT was shown.

PMID- 12805334
TI  - Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients
      with relapsed acute promyelocytic leukemia.
AB  - PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic
      response rate in patients with relapsed acute promyelocytic leukemia (APL).
      Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may
      strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and
      2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20
      patients with relapsed APL, all previously treated with ATRA-containing
      chemotherapy. The primary objective was to demonstrate a significant reduction in
      the time necessary to obtain a complete remission (CR) in the ATO/ATRA group
      compared with the ATO group. Secondary objectives were safety and molecular
      response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle
      was 80%. Clinical and pharmacokinetic observations indicated that the main
      mechanism of action of ATO in vivo was the induction of APL cell differentiation.
      Hematologic and molecular response, time necessary to reach CR, and outcome were
      comparable in both treatment groups. Of 16 CR patients, three patients who
      reached a molecular remission after one induction cycle had all received
      chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients
      who received further additional ATO with or without ATRA cycles converted later
      to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve
      the response to ATO in patients relapsing from APL. Other potential combinations,
      including ATO plus chemotherapy, have to be tested.

PMID- 12805335
TI  - Presentation serum selenium predicts for overall survival, dose delivery, and
      first treatment response in aggressive non-Hodgkin's lymphoma.
AB  - PURPOSE: This study was undertaken to test the hypothesis that serum selenium
      concentration at presentation correlates with dose delivery, first treatment
      response, and overall survival in patients with aggressive B-cell non-Hodgkin's
      lymphoma. PATIENTS AND METHODS: The patients presented between July 1986 and
      March 1999 and received anthracycline-based chemotherapy, radiotherapy, or both.
      The total selenium content was retrospectively analyzed in 100 sera, frozen at
      presentation, using inductively coupled plasma mass spectrometry. RESULTS: The
      serum selenium concentration ranged from 0.33 to 1.51 micromol/L (mean, 0.92
      micromol/L; United Kingdom adult reference range, 1.07 to 1.88 micromol/L). Serum
      selenium concentration correlated closely with performance status but with no
      other clinical variable. Multivariate analysis revealed that increased dose
      delivery, summarized by an area under the curve, correlated positively with
      younger age (P <.001), advanced stage (P =.001), and higher serum selenium
      concentration (P =.032). Selenium level also correlated positively with response
      (odds ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.90; P =.011) and
      achievement of long-term remission after first treatment (log-rank test, 4.38; P
      =.036). On multivariate analysis, selenium concentration was positively
      predictive of overall survival (hazard ratio [HR], 0.76 for 0.2 micromol/L
      increase; 95% CI, 0.60 to 0.95; P =.018), whereas age indicated negative
      borderline significance (HR, 1.09; 95% CI, 0.99 to 1.18; P =.066). CONCLUSION:
      Serum selenium concentration at presentation is a prognostic factor, predicting
      positively for dose delivery, treatment response, and long-term survival in
      aggressive non-Hodgkin's lymphoma. Unlike most existing prognostic factors in
      aggressive non-Hodgkin's lymphoma, selenium supplementation may offer a novel
      therapeutic strategy in this frequently curable malignancy.

PMID- 12805336
TI  - Immunization with Melan-A peptide-pulsed peripheral blood mononuclear cells plus
      recombinant human interleukin-12 induces clinical activity and T-cell responses
      in advanced melanoma.
AB  - PURPOSE: Preclinical studies showed that immunization with peripheral blood
      mononuclear cells (PBMC) loaded with tumor antigen peptides plus interleukin-12
      (IL-12) induced CD8+ T-cell responses and tumor rejection. We recently determined
      that recombinant human (rh) IL-12 at 30 to 100 ng/kg is effective as a vaccine
      adjuvant in patients. A phase II study of immunization with Melan-A peptide
      pulsed PBMC + rhIL-12 was conducted in 20 patients with advanced melanoma.
      PATIENTS AND METHODS: Patients were HLA-A2-positive and had documented Melan-A
      expression. Immunization was performed every 3 weeks with clinical re-evaluation
      every three cycles. Immune responses were measured by ELISpot assay before and
      after treatment and through the first three cycles, and were correlated with
      clinical outcome. RESULTS: Most patients had received prior therapy and had
      visceral metastases. Nonetheless, two patients achieved a complete response, five
      patients achieved a minor or mixed response, and four patients had stable
      disease. The median survival was 12.25 months for all patients and was not yet
      reached for those with a normal lactate dehydrogenase. There were no grade 3 or 4
      toxicities. Measurement of specific CD8+ T-cell responses by direct ex vivo
      ELISpot revealed a significant increase in interferon gamma-producing T cells
      against Melan-A (P =.015) after vaccination, but not against an Epstein-Barr
      virus control peptide (P =.86). There was a correlation between the magnitude of
      the increase in Melan-A-specific cells and clinical response (P =.046).
      CONCLUSION: This immunization approach may be more straightforward than dendritic
      cell strategies and seems to have clinical activity that can be correlated to a
      biologic end point.

PMID- 12805337
TI  - Long-term prospective follow-up study of cardiac function after cardiotoxic
      therapy for malignancy in children.
AB  - PURPOSE: To evaluate cardiac function by means of conventional and three
      dimensional echocardiography (3DE) and measurement of natriuretic peptides in
      children and adolescents previously treated for childhood malignancy using
      individual follow-up data and matched control children as reference criteria.
      PATIENTS AND METHODS: Thirty-nine survivors of childhood malignancy were examined
      in 1994 and 1998. The mean time from the diagnosis was 8.6 (3.9 to 16.8) years
      and between cardiac evaluations was 4.1 (3.3 to 5.1) years. Patients were divided
      into two groups according to therapies given (group I (n = 30): no cardiac
      irradiation, median cumulative anthracycline dose 210 mg/m2; group II (n = 9):
      irradiation in the cardiac region, median cumulative anthracycline dose 180
      mg/m2). RESULTS: Fractional shortening (FS) in 1994 was higher than in 1998 (32.5
      +/- 4.3 vs. 30.3% +/- 3.3%, P =.009). 33% of patients in group I and 56% in group
      II in 1994 and 30% of patients in group I and 67% in group II in 1998 had N
      terminal of the propeptide-atrial natriuretic peptide (NT-proANP) levels
      exceeding the 90th percentile of controls. In 1998, both groups (I and II) had
      lower ejection fraction (EF) measured by 3DE than their matched controls (52.9 +/
      5.2 vs. 58.8% +/- 3.1%, P <.001 and 50.0 +/- 6.6 vs. 60.8% +/- 3.2%, P =.024,
      respectively). Left atrial maximum volumes/body surface area were smaller in the
      patients than in controls. B-Type natriuretic peptide values did not differ
      significantly in either group. CONCLUSION: Left ventricular contractility
      decreases slowly even years after cardiotoxic cancer therapy in children. 3DE and
      NT-proANP measurements are effective methods to evaluate the cardiac function in
      these patients.

PMID- 12805338
TI  - Ovarian sex cord-stromal tumors in children and adolescents.
AB  - PURPOSE: To develop diagnostic standards and a risk-adapted therapeutic strategy
      for ovarian sex cord-stromal tumors (OSCST). PATIENTS AND METHODS: Fifty-four
      patients were prospectively enrolled as follow-up patients onto the German
      Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were
      reviewed centrally (53 patients with complete data). Surgery included ovariectomy
      in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one
      patient. Patients with stage IA tumors were followed-up at regular intervals,
      whereas nine patients with stage IC and six patients with stage II to III tumors
      were treated with cisplatin-based chemotherapy. RESULTS: International Federation
      of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II
      in three patients, and III in three patients. After a median follow-up of 59
      months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47
      of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients).
      Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27
      patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four
      of six patients]; P =.02). Ten of 15 patients treated with chemotherapy,
      including four of six stage II to III patients, are alive after a median follow
      up of 33 months. CONCLUSION: On the basis of a standardized clinical and
      histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be
      evaluated. Considering our experience, we would recommend that stage IA tumors be
      followed up at regular intervals, whereas we would recommend cisplatin-based
      chemotherapy in stage IC tumors with preoperative rupture or malignant ascites,
      especially those with high mitotic activity. Finally, cisplatin-based
      chemotherapy also seems to be effective in advanced-stage tumors.

PMID- 12805339
TI  - RSR13 plus cranial radiation therapy in patients with brain metastases:
      comparison with the Radiation Therapy Oncology Group Recursive Partitioning
      Analysis Brain Metastases Database.
AB  - PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and
      safety of the potential radiation enhancer RSR13 plus cranial radiation therapy
      (RT) in patients with brain metastases. The primary end point was patient
      survival in comparison with the Radiation Therapy Oncology Group Recursive
      Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND
      METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance
      score > or = 70, and brain metastases with solid tumor histology. Patients
      received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to
      100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons
      of survival and cause of death were made between class II study patients and RTOG
      BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a
      minimum follow-up of 24 months, the median survival time and 1- and 2-year
      survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients
      compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an
      exact-matched case analysis (n = 38), median survival time for RSR13 patients was
      7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54%
      reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related
      adverse events of greater than or equal to grade 3 toxicity that occurred in more
      than one patient included hypoxia, headache, anemia, fatigue, hypertension, and
      intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a
      significant improvement in survival, as well as a reduction in death due to brain
      metastases, compared with class II patients in the RTOG BMD.

PMID- 12805341
TI  - Summary statement on primary central nervous system lymphomas from the Eighth
      International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to
      15, 2002.
AB  - Under the sponsorship of the International Extranodal Lymphoma Study Group, a
      Multidisciplinary Workshop on primary CNS lymphoma (PCNSL) with over 50
      participants from Europe, North America, Israel, and Australia was held as part
      of the Eighth International Conference on Malignant Lymphoma in Lugano,
      Switzerland (June 12 to 15, 2002). The main purposes of the Workshop were to
      exchange the latest scientific information, to analyze methodologic issues in the
      design of clinical trials, to reach a consensus on treatment recommendations and
      prognostic factors, to discuss clinical and molecular targets for future studies,
      and to establish an international collaborative group to conduct laboratory and
      clinical investigations in PCNSL. This article summarizes the contents of the
      Workshop, analyzes the current knowledge on the most relevant biologic and
      clinical issues in PCNSL, and focuses on fundamental challenges to be addressed
      in future studies.

PMID- 12805340
TI  - Inhalation aromatherapy during radiotherapy: results of a placebo-controlled
      double-blind randomized trial.
AB  - PURPOSE: To determine whether the inhalation of aromatherapy during radiotherapy
      reduces anxiety. PATIENTS AND METHODS: Three hundred thirteen patients undergoing
      radiotherapy were randomly assigned to receive either carrier oil with
      fractionated oils, carrier oil only, or pure essential oils of lavender,
      bergamot, and cedarwood administered by inhalation concurrently with radiation
      treatment. Patients underwent assessment by the Hospital Anxiety and Depression
      Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline
      and at treatment completion. RESULTS: There were no significant differences in
      HADS depression or SPHERE scores between the randomly assigned groups. However,
      HADS anxiety scores were significantly lower at treatment completion in the
      carrier oil only group compared with either of the fragrant arms (P =.04).
      CONCLUSION: Aromatherapy, as administered in this study, is not beneficial.

PMID- 12805343
TI  - Teaching communication skills to medical oncology fellows.

PMID- 12805342
TI  - Current developments in cancer vaccines and cellular immunotherapy.
AB  - This article reviews the immunologic basis of clinical trials that test means of
      tumor antigen recognition and immune activation, with the goal to provide the
      clinician with a mechanistic understanding of ongoing cancer vaccine and cellular
      immunotherapy clinical trials. Multiple novel immunotherapy strategies have
      reached the stage of testing in clinical trials that were accelerated by recent
      advances in the characterization of tumor antigens and by a more precise
      knowledge of the regulation of cell-mediated immune responses. The key steps in
      the generation of an immune response to cancer cells include loading of tumor
      antigens onto antigen-presenting cells in vitro or in vivo, presenting antigen in
      the appropriate immune stimulatory environment, activating cytotoxic lymphocytes,
      and blocking autoregulatory control mechanisms. This knowledge has opened the
      door to antigen-specific immunization for cancer using tumor-derived proteins or
      RNA, or synthetically generated peptide epitopes, RNA, or DNA. The critical step
      of antigen presentation has been facilitated by the coadministration of powerful
      immunologic adjuvants, the provision of costimulatory molecules and immune
      stimulatory cytokines, and the ability to culture dendritic cells. Advances in
      the understanding of the nature of tumor antigens and their optimal presentation,
      and in the regulatory mechanisms that govern the immune system, have provided
      multiple novel immunotherapy intervention strategies that are being tested in
      clinical trials.

PMID- 12805344
TI  - Small-cell cancers, and an unusual reaction to chemotherapy. Case 1.
      Extrapulmonary small-cell carcinoma arising in the prostate.

PMID- 12805345
TI  - Small-cell cancers, and an unusual reaction to chemotherapy. Case 2. Synchronous
      renal cell carcinoma and limited-stage small-cell lung cancer.

PMID- 12805346
TI  - Small-cell cancers, and an unusual reaction to chemotherapy: Case 3. Small-cell
      carcinoma of the stomach.

PMID- 12805347
TI  - Small-cell cancers, and an unusual reaction to chemotherapy: Case 4. Fluorouracil
      related small bowel vasculitis.

PMID- 12805348
TI  - Can endocrine treatment for hormone-positive premenopausal women with early
      breast cancer replace adjuvant chemotherapy?

PMID- 12805349
TI  - Paradigm shift in adjuvant treatment of receptor positive premenopausal breast
      cancer patients? Not yet!

PMID- 12805351
TI  - Combined endocrine blockade in premenopausal breast cancer: a superior
      therapeutic option for adjuvant management?

PMID- 12805354
TI  - Correction to "Congestive heart failure after treatment for Wilms' tumor".

PMID- 12805355
TI  - The non-cyclooxygenase targets of non-steroidal anti-inflammatory drugs,
      lipoxygenases, peroxisome proliferator-activated receptor, inhibitor of kappa B
      kinase, and NF kappa B, do not reduce amyloid beta 42 production.
AB  - Epidemiological evidence suggests that chronic use of non-steroidal anti
      inflammatory drugs (NSAIDs) reduces the risk of Alzheimer's disease. Recently,
      NSAIDs have been shown to decrease amyloid pathology in a transgenic mouse model
      of Alzheimer's disease. This benefit may be partially attributable to the ability
      of NSAIDs to selectively reduce production of the amyloidogenic A beta 42 peptide
      in both cultured cells and transgenic mice. Although this activity does not
      appear to require the action of cyclooxygenases in cultured cells, it is not
      known whether other NSAID-sensitive targets contribute to this A beta 42 effect.
      In this study, we have used both pharmacological and genetic means to determine
      if other known cellular targets of NSAIDs could mediate the reduction in A beta
      42 secretion from cultured cells. We find that altered arachidonic acid
      metabolism via NSAID action on cyclooxygenases and lipoxygenases does not alter A
      beta 42 production. Furthermore, we demonstrate that alterations in activity of
      peroxisome proliferator-activated receptors, I kappa B kinase beta or nuclear
      factor kappa B do not affect A beta 42 production. Thus, NSAIDs do not appear to
      alter A beta 42 production indirectly through previously identified cellular
      targets and may interact directly with the gamma-secretase complex itself to
      affect amyloid production.

PMID- 12805356
TI  - Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42
      production by direct modulation of gamma-secretase activity.
AB  - Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a
      lower risk of developing Alzheimer's disease. Recent evidence indicates that some
      NSAIDs specifically inhibit secretion of the amyloidogenic A beta 42 peptide in
      cultured cells and mouse models of Alzheimer's disease. The reduction of A beta
      42 peptides is not mediated by inhibition of cyclooxygenases (COX) but the
      molecular mechanism underlying this novel activity of NSAIDs has not been further
      defined. We now demonstrate that NSAIDs efficiently reduce the intracellular pool
      of A beta 42 in cell-based studies and selectively decrease A beta 42 production
      in a cell-free assay of gamma-secretase activity. Moreover, we find that
      presenilin-1 (PS1) mutations, which affect gamma-secretase activity,
      differentially modulate the cellular A beta 42 response to NSAID treatment.
      Overexpression of the PS1-M146L mutation enhances the cellular drug response to A
      beta 42 lowering NSAIDs as compared with cells expressing wild-type PS1. In
      contrast, expression of the PS1-Delta Exon9 mutation strongly diminishes the A
      beta 42 response, showing that PS1 mutations can modulate the cellular drug
      response to NSAID treatment both positively and negatively. Enhancement of the
      NSAID drug response was also observed with overexpression of the APP V717F
      mutation but not with Swedish mutant APP, which affects beta-secretase cleavage.
      In sum, these results strongly suggest that NSAIDs represent a founding group of
      compounds that lower A beta 42 production by direct modulation of gamma-secretase
      activity or its substrate.

PMID- 12805357
TI  - Characterization of a trap mutant of the AAA+ chaperone ClpB.
AB  - The AAA+ protein ClpB mediates the solubilization of protein aggregates in
      cooperation with the DnaK chaperone system (KJE). The order of action of ClpB and
      KJE on aggregated proteins is unknown. We describe a ClpB variant with mutational
      alterations in the Walker B motif of both AAA domains (E279A/E678A), which binds
      but does not hydrolyze ATP. This variant associates in vitro and in vivo in a
      stable manner with protein substrates, demonstrating direct interaction of ClpB
      with protein aggregates for the first time. Substrate interaction is strictly
      dependent on ATP binding to both AAA domains of ClpB. The unique substrate
      binding properties of the double Walker B variant allowed to dissect the order of
      ClpB and DnaK action during disaggregation reactions. ClpB-E279A/E678A
      outcompetes the DnaK system for binding to the model substrate TrfA and inhibits
      the dissociation of small protein aggregates by DnaK only, indicating that ClpB
      acts prior to DnaK on protein substrates.

PMID- 12805358
TI  - Escherichia coli YrbH is a D-arabinose 5-phosphate isomerase.
AB  - A gene encoding for arabinose 5-phosphate isomerase (API), which catalyzes the
      interconversion of d-ribulose 5-phosphate (Ru5P) and d-arabinose 5-phosphate
      (A5P), has been identified from the genome of Escherichia coli K-12. API is the
      first enzyme in the biosynthesis of 3-deoxy-d-manno-octulosonate (KDO), a sugar
      moiety located in the lipopolysaccharide layer of most Gram-negative bacteria.
      The API gene yrbH is located next to the recently identified specific KDO 8-P
      phosphatase gene, yrbI. The 328-amino acid open reading frame yrbH was cloned,
      overexpressed, and characterized. The purified recombinant enzyme is a tetramer
      and is sensitive to inhibition by zinc cations. API has optimal activity at pH
      8.4 and catalytic residues with estimated pKa values of 6.55 +/- 0.04 and 10.34
      +/- 0.07. The enzyme is specific for A5P and Ru5P, with apparent Km values of
      0.61 +/- 0.06 mm for A5P and 0.35 +/- 0.08 mm for Ru5P. The apparent kcat in the
      A5P to Ru5P direction is 157 +/- 4 s-1, and in the Ru5P to A5P direction it is
      255 +/- 16 s-1. The value of Keq (Ru5P/A5P) is 0.50 +/- 0.06. Homology searches
      of the E. coli genome suggest yrbH may be one of multiple genes that encode
      proteins with API activity.

PMID- 12805359
TI  - Protein targeting to glycogen overexpression results in the specific enhancement
      of glycogen storage in 3T3-L1 adipocytes.
AB  - Protein phosphatase-1 (PP1) plays an important role in the regulation of glycogen
      synthesis by insulin. Protein targeting to glycogen (PTG) enhances glycogen
      accumulation by increasing PP1 activity against glycogen-metabolizing enzymes.
      However, the specificity of PTG's effects on cellular dephosphorylation and
      glucose metabolism is unclear. Overexpression of PTG in 3T3-L1 adipocytes using a
      doxycycline-controllable adenoviral construct resulted in a 10-20-fold increase
      in PTG levels and an 8-fold increase in glycogen levels. Inclusion of 1 microg/ml
      doxycycline in the media suppressed PTG expression, and fully reversed all PTG
      dependent effects. Infection of 3T3-L1 adipocytes with the PTG adenovirus caused
      a marked dephosphorylation and activation of glycogen synthase. The effects of
      PTG seemed specific, because basal and insulin-stimulated phosphorylation of a
      variety of signaling proteins was unaffected. Indeed, glycogen synthase was the
      predominant protein whose phosphorylation state was decreased in 32P-labeled
      cells. PTG overexpression did not alter PP1 protein levels but increased PP1
      activity 6-fold against phosphorylase in vitro. In contrast, there was no change
      in PP1 activity measured using myelin basic protein, suggesting that PTG
      overexpression specifically directed PP1 activity against glycogen-metabolizing
      enzymes. To investigate the metabolic consequences of altering PTG levels,
      glucose uptake and storage in 3T3-L1 adipocytes was measured. PTG overexpression
      did not affect 2-deoxy-glucose transport rates in basal and insulin-stimulated
      cells but dramatically enhanced glycogen synthesis rates under both conditions.
      Despite the large increases in cellular glucose flux upon PTG overexpression,
      basal and insulin-stimulated glucose incorporation into lipid were unchanged.
      Cumulatively, these data indicate that PTG overexpression in 3T3-L1 adipocytes
      discretely stimulates PP1 activity against glycogen synthase and phosphorylase,
      resulting in a marked and specific increase in glucose uptake and storage as
      glycogen.

PMID- 12805360
TI  - The host cell chaperone Hsp90 is essential for translocation of the binary
      Clostridium botulinum C2 toxin into the cytosol.
AB  - Clostridium botulinum C2 toxin is the prototype of the binary actin-ADP
      ribosylating toxins and consists of the binding component C2II and the enzyme
      component C2I. The activated binding component C2IIa forms heptamers, which bind
      to carbohydrates on the cell surface and interact with the enzyme component C2I.
      This toxin complex is taken up by receptor-mediated endocytosis. In acidic
      endosomes, heptameric C2IIa forms pores and mediates the translocation of C2I
      into the cytosol. We report that the heat shock protein (Hsp) 90-specific
      inhibitors, geldanamycin or radicicol, block intoxication of Vero cells, rat
      astrocytes, and HeLa cells by C2 toxin. ADP-ribosylation of actin in the cytosol
      of toxin-treated cells revealed that less active C2I was translocated into the
      cytosol after treatment with Hsp90 inhibitors. Under control conditions, C2I was
      localized in the cytosol of toxin-treated rat astrocytes, whereas geldanamycin
      blocked the cytosolic distribution of C2I. At low extracellular pH (pH 4.5),
      which allows the direct translocation of C2I via C2IIa heptamers across the cell
      membrane into the cytosol, Hsp90 inhibitors retarded intoxication by C2I.
      Geldanamycin did not affect toxin binding, endocytosis, and pore formation by
      C2IIa. The ADP-ribosyltransferase activity of C2I was not affected by Hsp90
      inhibitors in vitro. The cytotoxic actions of the actin-ADP-ribosylating
      Clostridium perfringens iota toxin and the Rho-ADP-ribosylating C2-C3 fusion
      toxin was similarly blocked by Hsp90 inhibitors. In contrast, radicicol and
      geldanamycin had no effect on anthrax lethal toxin-induced cytotoxicity of J774
      A1 macrophage-like cells or on cytotoxic effects of the glucosylating Clostridium
      difficile toxin B in Vero cells. The data indicate that Hsp90 is essential for
      the membrane translocation of ADP-ribosylating toxins delivered by C2II.

PMID- 12805361
TI  - Down-regulation of hypoxia-inducible factor-2 in PC12 cells by nerve growth
      factor stimulation.
AB  - Cellular responses to low oxygen tension are mediated, at least in part, by the
      activation of the hypoxia-inducible factors (HIFs). In the presence of oxygen,
      specific HIF residues become hydroxylated by the action of a recently described
      group of dioxygenases. These post-translational modifications target HIF for
      proteosomal degradation and prevent its transcriptional activity. Despite these
      detailed studies, little is known about the regulation of HIF by stimuli other
      than hypoxia. Here we report that, in rat pheochromocytoma PC12 cells, nerve
      growth factor (NGF) stimulation results in a decrease of both basal and hypoxia
      induced levels of HIF-2 alpha protein. NGF treatment did not increase HIF
      hydroxylase gene expression or activity, and the reduction of the HIF-2 alpha
      protein level upon stimulation was observed even in the presence of HIF
      hydroxylase inhibitors such as deferoxamine or dimethyloxoglutarate. Thus, in
      contrast to the response to hypoxia, the effect of NGF on HIF-2 alpha protein
      levels is not mediated by the HIF hydroxilases. Quantitative real time (RT)-PCR
      showed that NGF stimulation results in a decrease of the HIF-2 alpha mRNA level
      similar to that found at the protein level. Interestingly, NGF effect was
      specific for HIF-2 alpha mRNA because it did not affect HIF-1 alpha mRNA levels.
      NGF treatment reduced HIF-2 alpha mRNA levels even in the presence of actinomycin
      D, suggesting an effect on mRNA stability. Finally, the effect of NGF on HIF2
      alpha correlates with reduction of both basal and hypoxia-induced vascular
      endothelial growth factor mRNA levels. Reporter assays suggest that the reduced
      expression of hypoxia-inducible genes upon NGF treatment is related, at least in
      part, to the reduction of HIF-2 alpha protein. Hence, in PC12 cells the level of
      HIF-2 alpha protein and its effect on gene expression can be down-regulated by
      stimuli other than oxygen.

PMID- 12805362
TI  - Emergence and disappearance of an immune molecule, an antimicrobial lectin, in
      basal metazoa. A tachylectin-related protein in the sponge Suberites domuncula.
AB  - Sponges (phylum Porifera) represent the evolutionarily oldest metazoans that
      comprise already a complex immune system and are related to the crown taxa of the
      protostomians and the deuterostomians. Here, we demonstrate the existence of a
      tachylectin-related protein in the demosponge Suberites domuncula, termed
      Suberites lectin. The MAPK pathway was activated in response to
      lipopolysaccharide treatment of the three-dimensional cell aggregates, the
      primmorphs; this process was abolished by the monosaccharide D-GlcNAc. The cDNA
      encoding the S. domuncula lectin was identified and cloned; it comprises 238
      amino acids (26 kDa) in the open reading frame. The deduced protein has one
      potential transmembrane region, three characteristic Cys residues, and six
      internal tandem repeats; it shares the highest sequence similarity with lectins
      from the horseshoe crab Tachypleus trunculus. The steady-state level of
      expression of the Suberites lectin rises in primmorphs in response to
      lipopolysaccharide, an effect that was prevented by co-incubation with D-GlcNAc.
      The natural sponge lectin was purified by affinity chromatography; it has a size
      of 27 kDa and displays antibacterial activity against the Gram-negative bacteria
      Escherichia coli and the Gram-positive bacteria Staphylococcus aureus. The
      putative protein, deduced from the cloned gene, is identical/similar to the
      purified natural protein, as demonstrated by immunological cross-reactivity with
      specific antibodies. We conclude that the S. domuncula lectin acts as an
      antibacterial molecule involved in immune defense against bacterial invaders.

PMID- 12805363
TI  - Autosomal recessive hypercholesterolemia protein interacts with and regulates the
      cell surface level of Alzheimer's amyloid beta precursor protein.
AB  - The familial Alzheimer's disease gene product amyloid beta protein precursor (A
      beta PP) is sequentially processed by beta- and gamma-secretases to generate the
      A beta peptide. Although much is known about the biochemical pathway leading to A
      beta formation, because extracellular aggregates of A beta peptides are
      considered the cause of Alzheimer's disease, the biological role of A beta PP
      processing is only recently being investigated. Cleavage of A beta PP by gamma
      secretase releases, together with A beta, a COOH-terminal A beta PP intracellular
      domain, termed AID. Hoping to gain clues about proteins that regulates A beta PP
      processing and function, we used the yeast two-hybrid system to identify proteins
      that interact with the AID region of A beta PP. One of the interactors isolated
      is the autosomal recessive hypercholesterolemia (ARH) adapter protein. This
      molecular interaction is confirmed in vitro and in vivo by fluorescence resonance
      energy transfer and in cell lysates. Moreover, we show that reduction of ARH
      expression by RNA interference results in increased levels of cell membrane A
      beta PP. These data assert a physiological role for ARH in A beta PP
      internalization, transport, and/or processing.

PMID- 12805364
TI  - Artificial multimers of the type III antifreeze protein. Effects on thermal
      hysteresis and ice crystal morphology.
AB  - A variant of antifreeze protein (AFP) named RD3 from antarctic eel pout
      (Lycodichthys dearborni) comprises the type III AFP intramolecular dimer, which
      is known to exhibit a significant enhancement of thermal hysteresis when compared
      with the type III AFP monomer (Miura, K., Ohgiya, S., Hoshino, T, Nemoto, N.,
      Suetake, T., Miura, A, Spyracopoulos, L., Kondo, H., and Tsuda, S. (2001) J.
      Biol. Chem. 276, 1304-1310). Here we genetically synthesized intramolecular
      dimer, trimer, and tetramer of the type III AFP, for which we utilize the genes
      encoding the primary sequences of the N-domain, the C-domain, and the 9-residue
      linker of RD3, and we examined the AFP multimerization effects on thermal
      hysteresis and ice crystal morphology. Significantly, (i) the thermal hysteresis
      increases in proportion with the size of the multimers, (ii) a larger size of the
      multimer exerts the maximum activity at lower concentration, (iii) every multimer
      changes the morphology of a single ice crystal into a unique shape that is
      similar but not identical to the ordinary hexagonal bipyramid, and (iv) the size
      of ice crystal becomes dramatically small with increasing the concentration of
      the multimer. The thermal hysteresis enhancement of the multimer was detected in
      both molar and domain bases. These results suggest that a molecule comprising the
      multiple AFP domains connected in tandem acquires an enhanced affinity for the
      ice binding.

PMID- 12805365
TI  - Assembly of stable human type I and III collagen molecules from hydroxylated
      recombinant chains in the yeast Pichia pastoris. Effect of an engineered C
      terminal oligomerization domain foldon.
AB  - The C-propeptides of the pro alpha chains of type I and type III procollagens are
      believed to be essential for correct chain recognition and chain assembly in
      these molecules. We studied here whether the 30-kDa C-propeptides of the human pC
      alpha 1(I), pC alpha 2(I), and pC alpha 1(III) chains, i.e. pro alpha chains
      lacking their N-propeptides, can be replaced by foldon, a 29-amino acid sequence
      normally located at the C terminus of the polypeptide chains in the bacteriophage
      T4 fibritin. The alpha foldon chains were expressed in Pichia pastoris cells that
      also expressed the two types of subunit of human prolyl 4-hydroxylase; the foldon
      domain was subsequently removed by pepsin treatment, which also digests non
      triple helical collagen chains, whereas triple helical collagen molecules are
      resistant to it. The foldon domain was found to be very effective in chain
      assembly, as expression of the alpha 1(I)foldon or alpha 1(III)foldon chains gave
      about 2.5-3-fold the amount of pepsin-resistant type I or type III collagen
      homotrimers relative to those obtained using the authentic C-propeptides. In
      contrast, expression of chains with no oligomerization domain led to very low
      levels of pepsin-resistant molecules. Expression of alpha 2(I)foldon chains gave
      no pepsin-resistant molecules at all, indicating that in addition to control at
      the level of the C-propeptide other restrictions at the level of the collagen
      domain exist that prevent the formation of stable [alpha 2(I)]3 molecules. Co
      expression of alpha 1(I)foldon and alpha 2(I)foldon chains led to an efficient
      assembly of heterotrimeric molecules, their amounts being about 2-fold those
      obtained with the authentic C-propeptides and the alpha 1(I) to alpha 2(I) ratio
      being 1.91 +/- 0.31 (S.D.). As the foldon sequence contains no information for
      chain recognition, our data indicate that chain assembly is influenced not only
      by the C-terminal oligomerization domain but also by determinants present in the
      alpha chain domains.

PMID- 12805366
TI  - Microtubule-dependent oligomerization of tau. Implications for physiological tau
      function and tauopathies.
AB  - The accumulation of abnormal tau filaments is a pathological hallmark of many
      neurodegenerative diseases. In 1998, genetic analyses revealed a direct linkage
      between structural and regulatory mutations in the tau gene and the
      neurodegenerative disease, frontotemporal dementia with parkinsonism linked to
      chromosome 17 (FTDP-17). Importantly, the FTDP-17 phenotype is transmitted in a
      dominant rather than a recessive manner. However, the underlying molecular
      mechanisms causing disease remain uncertain. The most common molecular mechanism
      generating dominant phenotypes is the loss of function of a multimeric complex
      containing both mutant and wild-type subunits. Therefore, we sought to determine
      whether tau might normally function as a multimer. We co-incubated 35S
      radiolabeled tau and biotinylated tau with taxol stabilized microtubules, at very
      low molar ratios of tau to tubulin. Subsequent covalent cross-linking followed by
      affinity-precipitation of the biotinylated tau revealed the formation of
      microtubule-dependent tau oligomers. We next used atomic force microscopy to
      independently assess this conclusion. Our results are consistent with the
      hypothesis that tau forms oligomers upon binding to microtubules. In addition to
      providing insights into normal tau action, our findings lead us to propose that
      one mechanism by which mutations in tau may cause cell death is through the
      formation of tau complexes containing mutant tau molecules in association with
      wild-type tau. These wild-type-mutant tau complexes may possess altered
      biological and/or biophysical properties that promote onset of the FTDP-17
      phenotype, including neuronal cell death by either altering normal tau-mediated
      regulation of microtubule-dependent cellular functions and/or promoting the
      formation of pathological tau aggregates.

PMID- 12805367
TI  - New findings on interactions among the yeast oligosaccharyl transferase subunits
      using a chemical cross-linker.
AB  - At present, there is very limited knowledge about the structural organization of
      the yeast oligosaccharyl transferase (OT) complex and the function of each of its
      nine subunits. Because of the failure of the yeast two-hybrid system to reveal
      interactions between luminal domains of these subunits, we utilized a membrane
      permeable, thiocleavable cross-linking reagent dithiobis-succinimidyl propionate
      to biochemically study the interactions of various OT subunits. Four essential
      gene products, Ost1p, Wbp1p, Swp1p, and Stt3p were shown to be cross-linked to
      each other in a pairwise fashion. In addition, Ost1p was found to be cross-linked
      to all other eight OT subunits individually. This led us to propose that Ost1p
      may reside in the core of the OT complex and could play an important role in its
      assembly. Ost4p and Ost5p were found to only interact with specific components of
      the OT complex and may function as an additional anchor for optimal stability of
      Stt3p and Ost1p in the membrane, respectively. Interestingly, Ost3p and Ost6p
      subunits exhibited a surprisingly identical pattern of cross-linking to other
      subunits, which is consistent with their proposed redundant function. Based on
      these findings, we analyzed the distribution of the lysine residues that are
      likely to be involved in cross-linking of OT subunits and propose that the OT
      subunits interact with each other through either their transmembrane domains
      and/or a region proximal to it, rather than through their luminal or cytoplasmic
      domains.

PMID- 12805368
TI  - GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin
      contamination in NF-kappa B activation and nitric oxide production.
AB  - Vaccination of mice with GRP94/gp96, the endoplasmic reticulum Hsp90, elicits a
      variety of immune responses sufficient for tumor rejection and the suppression of
      metastatic tumor progression. Macrophages are a prominent GRP94/gp96 target, with
      GRP94/gp96 reported to activate macrophage NF-kappa B signaling and nitric oxide
      production, as well as the MAP kinase p38, JNK, and ERK signaling cascades.
      However, recent studies report that heat shock protein elicited macrophage
      activation is due, in large part, to contaminating endotoxin. To examine the
      generality of this finding, we have investigated the role of endotoxin in
      GRP94/gp96-elicited macrophage activation. We report that GRP94/gp96 binds
      endotoxin in a high-affinity, saturable, and specific manner. Low endotoxin
      calreticulin and GRP94/gp96 were purified, the latter using a novel method of
      depyrogenation; this resulted in GRP94/gp96 and calreticulin preparations with
      endotoxin levels substantially lower than those of previously reported
      preparations. Low endotoxin GRP94/gp96 retained its native conformation, ligand
      binding activity, and in vitro chaperone function, yet did not activate
      macrophage NF-kappa B signaling, nitric oxide production or inducible nitric
      oxide synthase production. Low endotoxin GRP94/gp96 and calreticulin did,
      however, elicit a marked increase in ERK phosphorylation at protein
      concentrations as low as 2 microg/ml. These results are discussed with respect to
      current understanding of the contributions of endotoxin and heat shock/chaperone
      proteins to the stimulation of innate immune responses.

PMID- 12805369
TI  - The transcription factor CCAAT-binding factor CBF/NF-Y regulates the proximal
      promoter activity in the human alpha 1(XI) collagen gene (COL11A1).
AB  - We have characterized the proximal promoter region of the human COL11A1 gene.
      Transient transfection assays indicate that the segment from -199 to +1 is
      necessary for the activation of basal transcription. Electrophoretic mobility
      shift assays (EMSAs) demonstrated that the ATTGG sequence, within the -147 to 
      121 fragment, is critical to bind nuclear proteins in the proximal COL11A1
      promoter. We demonstrated that the CCAAT binding factor (CBF/NF-Y) bound to this
      region using an interference assay with consensus oligonucleotides and a
      supershift assay with specific antibodies in an EMSA. In a chromatin
      immunoprecipitation assay and EMSA using DNA-affinity-purified proteins, CBF/NF-Y
      proteins directly bound this region in vitro and in vivo. We also showed that
      four tandem copies of the CBF/NF-Y-binding fragment produced higher
      transcriptional activity than one or two copies, whereas the absence of a CBF/NF
      Y-binding fragment suppressed the COL11A1 promoter activity. Furthermore,
      overexpression of a dominant-negative CBF-B/NF-YA subunit significantly inhibited
      promoter activity in both transient and stable cells. These results indicate that
      the CBF/NF-Y proteins regulate the transcription of COL11A1 by directly binding
      to the ATTGG sequence in the proximal promoter region.

PMID- 12805370
TI  - Identification of distinct sequences in human blood coagulation factor Xa and
      prothrombin essential for substrate and cofactor recognition in the
      prothrombinase complex.
AB  - To identify amino acid sequences in factor Xa (fXa) and prothrombin (fII) that
      may be involved in prothrombinase complex (fXa.factor Va.fII.phospholipids)
      assembly, synthetic peptides based on fXa and fII sequences were prepared and
      screened for their ability to inhibit fXa-induced clotting of normal plasma. One
      fII peptide (PT557-571 homologous to chymotrypsin (CHT) residues 225-239) and two
      fXa peptides (X404-418, CHT231-244, and X415-429, CHT241-252C) potently inhibited
      plasma clotting and prothrombinase activity with 50% inhibition between 41 and
      115 microM peptide. Inhibition of prothrombinase by PT557-571 and X415-429 was
      fVa-independent, whereas the inhibition by X404-418 was fVa-dependent. X404-418
      inhibited the binding of fVa to fluorescein-labeled, inhibited fXai in the
      presence of phosphatidylcholine/phosphatidylserine vesicles, whereas X415-429
      inhibited binding of fII to phospholipid-bound fluorescein-labeled, inhibited
      fXai. PT557-571 altered the fluorescence emission of fluorescein-labeled fXai,
      showing that PT557-571 binds to fXai. These data suggest that residues 404-418 in
      fXa provide fVa binding sites, whereas residues 557-571 in fII and 415-429 in fXa
      mediate interactions between fXa and fII in the prothrombinase complex.

PMID- 12805371
TI  - The Escherichia coli RecQ helicase functions as a monomer.
AB  - The RecQ helicases belong to an important family of highly conserved DNA
      helicases that play a key role in chromosomal maintenance, and their defects have
      been shown to lead to several disorders and cancer in humans. In this work, the
      conformational and functional properties of the Escherichia coli RecQ helicase
      have been determined using a wide array of biochemical and biophysical
      techniques. The results obtained clearly indicate that E. coli RecQ helicase is
      monomeric in solution up to a concentration of 20 microM and in a temperature
      range between 4 and 37 degrees C. Furthermore, these properties are not affected
      by the presence of ATP, which is strictly required for the unwinding and
      translocating activity of the protein, or by its nonhydrolyzable analogue 5'
      adenylyl-beta,gamma-imidodiphosphate. Consistent with the structural properties,
      functional analysis shows that both DNA unwinding activity and single-stranded
      DNA-stimulated ATPase specific activity were independent of RecQ concentration.
      The monomeric state was further confirmed by the ATPase-deficient mutants of RecQ
      protein. The rate of unwinding was unchanged when the wild type RecQ helicase was
      mixed with the ATPase-deficient mutants, indicating that nonprotein-protein
      interactions were involved in the unwinding processes. Taken together, these
      results indicate that RecQ helicase functions as a monomer and provide new data
      on the structural and functional properties of RecQ helicase that may help
      elucidate its mechanism action.

PMID- 12805372
TI  - Diverse but overlapping functions of the two forkhead-associated (FHA) domains in
      Rad53 checkpoint kinase activation.
AB  - Forkhead-associated (FHA) domains are phosphothreonine-binding modules prevalent
      in proteins with important cell cycle and DNA damage response functions. The
      yeast checkpoint kinase Rad53 is unique in containing two FHA domains. We have
      generated novel recessive rad53 alleles with abolished FHA domain functions
      resulting from Ala substitution of the critical phosphothreonine-binding residues
      Arg70 and Arg605. In asynchronous cells, inactivation of the N-terminal FHA1
      domain did not impair Rad53 activation and downstream functions, whereas
      inactivation of the C-terminal FHA2 domain led to reduced Rad53 activation and
      significantly increased DNA damage sensitivity. Simultaneous inactivation of both
      FHA domains abolished Rad53 activation and all downstream functions and
      dramatically increased the sensitivity to DNA damage and replication blocks
      similar to kinase-defective and rad53 null alleles, but did not compromise the
      essential viability function of Rad53. Interestingly, in G2/M synchronized cells,
      mutation of either FHA domain prevented Rad53 activation and impaired the cell
      cycle arrest checkpoint. Our data demonstrate that both FHA domains are required
      for normal Rad53 functions and indicate that the two FHA domains have
      differential but partially overlapping roles in Rad53 activation and downstream
      signaling.

PMID- 12805373
TI  - Dissecting the cellular functions of annexin XI using recombinant human annexin
      XI-specific autoantibodies cloned by phage display.
AB  - Functional studies of cellular proteins are often complicated by the lack of well
      defined monoclonal antibodies, the production of which is hampered by the highly
      conserved nature of these cellular proteins across species. Annexin XI, a member
      of the Ca2+-dependent, phospholipid-binding protein family, is an example of such
      a protein and was used in studies to devise a strategy using human autoimmune
      phage display libraries to generate reagents for biological studies of conserved
      cellular proteins. An IgG phage display library was generated from bone marrow of
      an autoimmune patient with high serum antibody titer against annexin XI, which
      was identified recently as an autoantigen targeted by autoantibodies in several
      systemic autoimmune diseases. From this phage library, a panel of human
      monoclonal annexin XI-specific Fabs were isolated and applied to studies of the
      cellular functions of annexin XI. Confocal microscopy showed a cell cycle
      specific redistribution of annexin XI from the cytoplasm to the mitotic spindle.
      In metaphase, annexin XI was up-regulated and costained with alpha-tubulin. The
      subcellular distribution of annexin XI in COS-7 cells was shown to be Ca2+
      dependent, and exhibited a predominantly nuclear pattern at low concentrations
      and a cytoplasmic pattern at high Ca2+ concentrations. Calcyclin, found
      previously to bind annexin XI in vitro, in vivo coated the nuclear membrane of
      cultured cell lines and did not colocalize with annexin XI. Ultrastructural
      analysis by immunoelectron microscopy revealed that annexin XI associated with
      specific granules in both neutrophils and eosinophils, suggesting a role in the
      exocytotic pathway. Our results illuminate the multifunctional nature of human
      annexin XI, provide the first evidence that annexin XI associates with the
      mitotic spindles and might play a role in cell division, and clearly illustrate
      the potential of phage display-derived human autoantibodies in broader analyses
      of the function of highly conserved cellular proteins.

PMID- 12805374
TI  - Liver peroxisome proliferator-activated receptor gamma contributes to hepatic
      steatosis, triglyceride clearance, and regulation of body fat mass.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear
      receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma
      is present in adipose tissue and becomes elevated in fatty livers, but the roles
      of specific tissues in thiazolidinedione actions are unclear. We studied the
      function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type
      mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis
      but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin
      resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic
      and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of
      adipose tissue, the liver is a primary and major site of thiazolidinedione
      action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice
      lacking liver PPAR gamma, suggesting that adipose tissue is the major site of
      thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice
      without liver PPAR gamma, but with adipose tissue, developed relative fat
      intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus,
      liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic
      steatosis, but protecting other tissues from triglyceride accumulation and
      insulin resistance.

PMID- 12805375
TI  - Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role
      for cardiolipin.
AB  - Little is known about the biochemical basis of the action of free fatty acids
      (FFA) on breast cancer cell proliferation and apoptosis. Here we report that
      unsaturated FFAs stimulated the proliferation of human MDA-MB-231 breast cancer
      cells, whereas saturated FFAs inhibited it and caused apoptosis. Saturated FFA
      palmitate decreased the mitochondrial membrane potential and caused cytochrome c
      release. Palmitate-induced apoptosis was enhanced by the fat oxidation inhibitor
      etomoxir, whereas it was reduced by fatty-acyl CoA synthase inhibitor triacsin C.
      The non-metabolizable analog 2-bromopalmitate was not cytotoxic. This indicates
      that palmitate must be metabolized to exert its toxic effect but that its action
      does not involve fat oxidation. Pharmacological studies showed that the action of
      palmitate is not mediated via ceramides, reactive oxygen species, or changes in
      phosphatidylinositol 3-kinase activity. Palmitate caused early enhancement of
      cardiolipin turnover and decreased the levels of this mitochondrial phospholipid,
      which is necessary for cytochrome c retention. Cosupplementation of oleate, or
      increasing beta-oxidation with the AMP-activated protein kinase activator, 5
      aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside, both restored cardiolipin
      levels and blocked palmitate-induced apoptosis. Oleate was preferentially
      metabolized to triglycerides, and oleate cosupplementation channeled palmitate
      esterification processes to triglycerides. Overexpression of Bcl-2 family members
      blocked palmitate-induced apoptosis. The results provide evidence that a decrease
      in cardiolipin levels and altered mitochondrial function are involved in
      palmitate-induced breast cancer cell death. They also suggest that the
      antiapoptotic action of oleate on palmitate-induced cell death involves both
      restoration of cardiolipin levels and redirection of palmitate esterification
      processes to triglycerides.

PMID- 12805376
TI  - CRIM1 regulates the rate of processing and delivery of bone morphogenetic
      proteins to the cell surface.
AB  - The Crim1 gene is predicted to encode a transmembrane protein containing six von
      Willebrand-like cysteine-rich repeats (CRRs) similar to those in the BMP-binding
      antagonist Chordin (Chrd). In this study, we verify that CRIM1 is a glycosylated,
      Type I transmembrane protein and demonstrate that the extracellular CRR
      containing domain can also be secreted, presumably via processing at the
      membrane. We have previously demonstrated Crim1 expression at sites consistent
      with an interaction with bone morphogenetic proteins (BMPs). Here we show that
      CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the
      protein and in so doing acts as an antagonist in three ways. CRIM1 binding of
      BMP4 and -7 occurs when these proteins are co-expressed within the Golgi
      compartment of the cell and leads to (i) a reduction in the production and
      processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell
      surface, and (iii) an effective reduction in the secretion of mature BMP.
      Functional antagonism was verified by examining the effect of co-expression of
      CRIM1 and BMP4 on metanephric explant culture. The presence of CRIM1 reduced the
      effective BMP4 concentration of the media, thereby acting as a BMP4 antagonist.
      Hence, CRIM1 modulates BMP activity by affecting its processing and delivery to
      the cell surface.

PMID- 12805377
TI  - Structural basis for the signaling specificity of RhoG and Rac1 GTPases.
AB  - RhoG is a new GTPase that has high sequence similarity with members of the Rac
      subfamily (Rac1, Rac2, and Rac3), including the regions involved in effector
      recognition and binding. To characterize its biological properties, we have
      compared the activity of RhoG and Rac1 in a number of experimental systems,
      including the study of their subcellular localization, oncogenic potential,
      activation of effectors, and effect on F-actin dynamics. Our study indicates that
      RhoG and Rac1 share overlapping, but not identical, signal transduction pathways.
      In contrast to previous results, we also provide evidence that RhoG works in
      parallel to Rac1 rather than as a Rac1 upstream activator. Using an extensive
      collection of Rho/Rac1 chimeras and point mutants, we demonstrate that the
      different biological properties of RhoG and Rac1 can be traced to specific amino
      acid variations in their switch I, beta2/beta3 hairpin, alpha5 helix, and C
      terminal polybasic regions. Taken collectively, our results highlight the
      complexity of the signal transduction pathways activated by Rho/Rac GTPases and
      provide insight into the structural determinants that mediate the differential
      engagement of biological responses by GTPases of very similar structure.

PMID- 12805379
TI  - K-ras regulates the steady-state expression of matrix metalloproteinase 2 in
      fibroblasts.
AB  - Fibroblasts constitutively express matrix metalloproteinase 2 (MMP-2), which
      specifically cleaves type IV collagen, a major structural component of basement
      membranes. The level of MMP-2 expression was not altered by serum withdrawal,
      suggesting that MMP-2 expression is regulated by a series of steady-state
      conditions that impinge on the MMP-2 promoter. Expression of a dominant-negative
      Ras protein significantly inhibited MMP-2 transcription, thereby suggesting a
      role for steady-state Ras function in the regulation of MMP-2 expression. Kirsten
      Ras (K-Ras) knockout fibroblasts express undetectable basal levels of MMP-2,
      whereas N-Ras knockout fibroblasts expressed constitutive levels of MMP-2 similar
      to those observed in wild-type control fibroblasts. Using an MMP-2 promoter
      luciferase reporter assay, we demonstrated that the transcription of MMP-2 in K
      Ras knockout fibroblasts was partially restored by transient expression of c-K(B)
      Ras but not c-K(A)-Ras. A phosphoinositide-3 (PI-3) kinase-specific inhibitor
      (LY294002) decreased the basal level of MMP-2 in wild-type fibroblasts. Blocking
      PI-3 kinase signaling by overexpression of the regulatory domain of PI-3 kinase
      (p85) also down-regulated the steady-state MMP-2 levels. Fibroblasts that fail to
      express AKT1 also expressed decreased amounts of MMP-2 compared with wild-type
      fibroblasts. These data suggest that steady-state MMP-2 expression is regulated
      by c-K(B)-Ras through a PI-3 kinase:AKT-dependent signaling pathway. Because the
      majority of the MMP-2 assays were performed using conditioned media from serum
      starved fibroblasts, these data also highlight our previous observations that Ras
      proteins have functions in the absence of acute mitogenic stimulations. In
      addition, this is the first demonstration of a specific steady-state function
      attributable to K(B)-Ras.

PMID- 12805380
TI  - Heat and heavy metal stress synergize to mediate transcriptional hyperactivation
      by metal-responsive transcription factor MTF-1.
AB  - Mammalian cells react to heavy metal stress by transcribing a number of genes
      that contain metal-response elements (MREs) in their promoter/enhancer region;
      this activation is mediated by metal-responsive transcription factor-1 (MTF-1).
      Well-known target genes of MTF-1 are those encoding metallothioneins, small,
      cysteine-rich proteins with a high affinity for heavy metals. The response to
      heat shock, another cell stress, is mediated by heat shock transcription factor 1
      (HSF1), which activates a battery of heat shock genes. Little is known about the
      cross-talk between the different anti-stress systems of the cell. Here we report
      a synergistic activation of metal-responsive promoters by heavy metal load (zinc
      or cadmium) and heat shock. An obvious explanation, cooperativity between MTF-1
      and HSF1, seems unlikely: transfected HSF1 boosts the activity of an Hsp70
      promoter but hardly affects an MRE-containing promoter upon exposure to metal and
      heat shock. A clue to the mechanism is given by our finding that heat shock leads
      to intracellular accumulation of heavy metals. We propose that the known anti
      apoptotic effect of heat shock proteins allows for cell survival despite heavy
      metal accumulation and, consequently, results in a hyperactivation of the metal
      response pathway.

PMID- 12805378
TI  - Activation of protein kinase C delta by all-trans-retinoic acid.
AB  - All-trans-retinoic acid (RA) is a potent inhibitor of leukemia cell proliferation
      and induces differentiation of acute promyelocytic leukemia cells in vitro and in
      vivo. For RA to induce its biological effects in target cells, binding to
      specific retinoic acid nuclear receptors is required. The resulting complexes
      bind to RA-responsive elements (RAREs) in the promoters of RA-inducible genes to
      initiate gene transcription and to generate protein products that mediate the
      biological effects of RA. In this report, we provide evidence that a member of
      the protein kinase C (PKC) family of proteins, PKC delta, is activated during RA
      treatment of the NB-4 and HL-60 acute myeloid leukemia cell lines as well as the
      MCF-7 breast cancer cell line. Such RA-dependent phosphorylation was also
      observed in primary acute promyelocytic leukemia cells and resulted in activation
      of the kinase domain of PKC delta. In studies aimed at understanding the
      functional relevance of PKC delta in the induction of RA responses, we found that
      pharmacological inhibition of PKC delta (but not of other PKC isoforms)
      diminished RA-dependent gene transcription via RAREs. On the other hand,
      overexpression of a constitutively active form of the kinase strongly enhanced RA
      dependent gene transcription via RAREs. Gel shift assays and chromatin
      immunoprecipitation studies demonstrated that PKC delta associated with retinoic
      acid receptor-alpha and was present in an RA-inducible protein complex that bound
      to RAREs. Pharmacological inhibition of PKC delta activity abrogated the
      induction of cell differentiation and growth inhibition of NB-4 blast cells,
      demonstrating that its function is required for such effects. Altogether, our
      data provide strong evidence that PKC delta is activated in an RA-dependent
      manner and plays a critical role in the generation of the biological effects of
      RA in malignant cells.

PMID- 12805381
TI  - The conversion of fibrinogen to fibrin at the surface of curliated Escherichia
      coli bacteria leads to the generation of proinflammatory fibrinopeptides.
AB  - The inflammatory response to bacterial infection is the result of a complex
      interplay between bacterial products and host effector systems, such as the
      immune and complement systems. Here we show that Escherichia coli bacteria
      expressing fibrous surface proteins, known as curli, assemble and activate
      factors of the human coagulation cascade at their surface. As a result of this
      interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides,
      termed fibrinopeptides, are generated. The molecular mechanisms behind the
      bacteria-induced formation of fibrinopeptides were investigated and shown to be
      triggered by the activation of the contact system, also known as the
      kallikrein/kinin system or the intrinsic pathway of coagulation. Samples
      containing fibrinopeptides generated by the interaction between bacteria and
      plasma were injected into animals and the inflammatory response was monitored. We
      found that this treatment provoked an infiltration of white blood cells, and the
      induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results
      therefore demonstrate that activation of the coagulation system at the bacterial
      surface contributes to the pathophysiology of bacterial infectious diseases.

PMID- 12805382
TI  - Hepatitis B virus X protein activates a survival signaling by linking SRC to
      phosphatidylinositol 3-kinase.
AB  - We have previously shown that transactivation-proficient hepatitis virus B X
      protein (HBx) protects Hep 3B cells from transforming growth factor-beta (TGF
      beta)-induced apoptosis via activation of the phosphatidylinositol 3-kinase (PI 3
      kinase)/Akt signaling pathway. This work further investigated how HBx activates
      PI 3-kinase. Src activity was elevated in Hep 3B cells following expression of
      transactivation-proficient HBx or HBx-GFP fusion proteins. The Src family kinase
      inhibitor PP2 and C-terminal Src kinase (Csk) both alleviated HBx-mediated PI 3
      kinase activation and protection from TGF-beta-induced apoptosis. Therefore, HBx
      activated a survival signal by linking Src to PI 3-kinase. Systemic subcellular
      fractionation and membrane flotation assays indicated that approximately 1.5% of
      ectopically expressed HBxGFP was associated with periplasmic membrane where Src
      was located. However, neither nucleus-targeted nor periplasmic membrane-targeted
      HBxGFP was able to upregulate Src activity or to augment PI 3-kinase survival
      signaling pathway.

PMID- 12805383
TI  - A novel double heme substitution produces a functional bo3 variant of the quinol
      oxidase aa3 of Bacillus cereus. Purification and paratial characterization.
AB  - A novel bo3-type quinol oxidase was highly purified from Bacillus cereus PYM1, a
      spontaneous mutant unable to synthesize heme A and therefore spectroscopically
      detectable cytochromes aa3 and caa3. The purified enzyme contained 12.4 nmol of
      heme O and 11.5 nmol of heme B mg-1 protein. The enzyme was composed of two
      subunits with an Mr of 51,000 and 30,000, respectively. Both subunits were
      immunoreactive to antibodies raised against the B cereus aa3 oxidase. Moreover,
      amino-terminal sequence analysis of the 30-kDa subunit revealed that the first 19
      residues were identical to those from the 30-kDa subunit of the B. cereus aa3
      oxidase. The purified bo3 oxidase failed to oxidize ferrrocytochrome c (neither
      yeast nor horse) but oxidized tetrachlorohydroquinol with an apparent Km of 498
      microM, a Vmax of 21 micromol of O2 min-1mg-1, and a calculated turnover of 55 s
      1. The quinol oxidase activity with tetrachlorohydroquinol was inhibited by
      potassium cyanide and 2-n-heptyl 4-hydroxyquinoline-N-oxide with an I50 of 24 and
      300 microM, respectively. Our results demonstrate that the bo3 oxidase of this
      mutant is not the product of a new operon but instead is a cytochrome aa3
      apoprotein encoded by the qox operon of the aa3 oxidase of B. cereus wild type
      promiscuously assembled with hemes B and O replacing heme A, producing a novel
      bo3 cytochrome. This is the first reported example of an enzymatically active
      promiscuous oxidase resulting from the simultaneous substitution of its original
      hemes in the high and low spin sites.

PMID- 12805384
TI  - STAT4 requires the N-terminal domain for efficient phosphorylation.
AB  - STAT4 (signal transducer and activator of transcription-4) mediates biological
      effects in response to interleukin-12 (IL-12). STAT4 has multiple domains that
      have distinct functions in signaling and gene activation. To characterize the
      role of the STAT4 N-terminal domain in mediating STAT4 biological function, we
      have generated STAT4-deficient transgenic mice that express human full-length
      STAT4 or an N-terminal deletion mutant (Delta N-STAT4) lacking the N-terminal 51
      amino acids. Whereas full-length STAT4 rescued IL-12 responsiveness, T
      lymphocytes expressing the STAT4 N-terminal mutant failed to proliferate in
      response to IL-12 and had limited Th1 cell development as evidenced by minimal
      interferon-gamma production. Deletion of the N-terminal domain resulted in
      failure of STAT4 to be phosphorylated following IL-12 stimulation despite similar
      phosphorylation of JAK2 and TYK2 in full-length STAT4 and Delta N-STAT4
      transgenic T cells. We demonstrate that the lack of phosphorylation in cultured
      cells is due to reduced efficiency of phosphorylation of Delta N-STAT4 by Janus
      kinases. These data support a new model wherein the N-terminal domain is required
      to mediate the phosphorylation of STAT4 in addition to the previously documented
      role in gene transactivation.

PMID- 12805385
TI  - phi 29 DNA polymerase residue Leu384, highly conserved in motif B of eukaryotic
      type DNA replicases, is involved in nucleotide insertion fidelity.
AB  - Replicative DNA polymerases achieve insertion fidelity by geometric selection of
      a complementary nucleotide followed by induced fit: movement of the fingers
      subdomain toward the active site to enclose the incoming and templating
      nucleotides generating a binding pocket for the nascent base pair. Several
      residues of motif B of DNA polymerases from families A and B, localized in the
      fingers subdomain, have been described to be involved in template/primer binding
      and dNTP selection. Here we complete the analysis of this motif, which has the
      consensus "KLX2NSXYG" in DNA polymerases from family B, characterized by
      mutational analysis of conserved leucine, Leu384 of phi 29 DNA polymerase.
      Mutation of Leu384 into Arg resulted in a phi 29 DNA polymerase with reduced
      nucleotide insertion fidelity during DNA-primed polymerization and protein-primed
      initiation reactions. However, the mutation did not alter the intrinsic affinity
      for the different dNTPs, as shown in the template-independent terminal protein
      deoxynucleotidylation reaction. We conclude that Leu384 of phi 29 DNA polymerase
      plays an important role in positioning the templating nucleotide at the
      polymerization active site and in controlling nucleotide insertion fidelity. This
      agrees with the localization of the corresponding residue in the closed ternary
      complexes of family A and family B DNA polymerases, contributing to form the
      binding pocket for the nascent base pair. As an additional effect, mutant
      polymerase L384R was strongly reduced in DNA binding, resulting in reduced
      processivity during polymerization.

PMID- 12805386
TI  - Chemical identification of serine 181 at the ATP-binding site of myosin as a
      residue esterified selectively by the fluorescent reagent 9-anthroylnitrile.
AB  - The esterification reagent 9-anthroylnitrile (ANN) reacts with a serine residue
      in the NH2-terminal 23-kDa peptide segment of myosin subfragment-1 heavy chain to
      yield a fluorescent S1 derivative labeled by the anthroyl group (Hiratsuka, T.
      (1989) J. Biol. Chem. 264, 18188-18194). The labeling was highly selective and
      accelerated by nucleotides. In the present study, to determine the exact location
      of the labeled serine residue, the labeled 23-kDa peptide fragment was isolated.
      The subsequent extensive proteolytic digestion of the peptide fragment yielded
      two labeled peptides, a pentapeptide and its precursor nonapeptide. Amino acid
      sequence and composition analyses of both labeled peptides revealed that the
      anthroyl group is attached to Ser-181 involved in the phosphate binding loop for
      ATP (Smith, C. A., and Rayment, I. (1996) Biochemistry 35, 5404-5417). We
      concluded that ANN can esterify Ser-181 selectively out of over 40 serine
      residues in the subfragment 1 heavy chain. Thus ANN is proved to be a valuable
      fluorescent tool to identify peptides containing the phosphate binding loop of S1
      and to detect the conformational changes around this loop.

PMID- 12805387
TI  - Nitric-oxide synthase (NOS) reductase domain models suggest a new control element
      in endothelial NOS that attenuates calmodulin-dependent activity.
AB  - Inducible (iNOS) and constitutive (eNOS, nNOS) nitric-oxide synthases differ in
      their Ca2+-calmodulin (CaM) dependence. iNOS binds CaM irreversibly but eNOS and
      nNOS, which bind CaM reversibly, have inserts in their reductase domains that
      regulate electron transfer. These include the 43-45-amino acid autoinhibitory
      element (AI) that attenuates electron transfer in the absence of CaM, and the C
      terminal 20-40-amino acid tail that attenuates electron transfer in a CaM
      independent manner. We constructed models of the reductase domains of the three
      NOS isoforms to predict the structural basis for CaM-dependent regulation. We
      have identified and characterized a loop (CD2A) within the NOS connecting domain
      that is highly conserved by isoform and that, like the AI element, is within
      direct interaction distance of the CaM binding region. The eNOS CD2A loop (eCD2A)
      has the sequence 834KGSPGGPPPG843, and is truncated to 809ESGSY813 (iCD2A) in
      iNOS. The eCD2A contributes to the Ca2+ dependence of CaM-bound activity to a
      level similar to that of the AI element. The eCD2A plays an autoinhibitory role
      in the control of NO, and CaM-dependent and -independent reductase activity, but
      this autoinhibitory function is masked by the dominant AI element. Finally, the
      iCD2A is involved in determining the salt dependence of NO activity at a post
      flavin reduction level. Electrostatic interactions between the CD2A loop and the
      CaM-binding region, and CaM itself, provide a structural means for the CD2A to
      mediate CaM regulation of intra-subunit electron transfer within the active NOS
      complex.

PMID- 12805388
TI  - Perillyl alcohol as a radio-/chemosensitizer in malignant glioma.
AB  - The prognosis for patients with malignant glioma has not significantly changed in
      two decades, despite advances in surgery, radiation, and chemotherapy,
      emphasizing the growing need for novel approaches to glioma therapy. Perillyl
      alcohol (POH) is a naturally occurring monoterpene that has been shown to possess
      chemotherapeutic as well as chemopreventive activity in animal tumor models and
      is currently in Phase I and Phase II clinical trials. In the present study, we
      have demonstrated that POH is an effective radiosensitizer at clinically relevant
      doses of radiation using established glioma cell lines. POH caused a transient
      arrest in the G2/M phase of the cell cycle and induced apoptosis in glioma cells.
      POH treatment sensitized glioma cells to Fas-mediated apoptosis, which was
      further augmented in the presence of ionizing radiation and abrogated in the
      presence of antagonistic antibody. POH-induced radiosensitization was partially
      inhibited in glioma cells expressing dominant negative Fas-associated death
      domain and completely inhibited in glioma cells overexpressing the cytokine
      response modifier A. In addition, POH treatment resulted in a dose-dependent
      sensitization to cisplatin and doxorubicin induced cytotoxicity in glioma cells,
      highlighting its usefulness as a potent radio/chemosensitizer in the treatment of
      malignant glioma.

PMID- 12805389
TI  - Sex hormones and sexual function in obese men losing weight.
AB  - OBJECTIVE: To study the impact of a weight-loss program on sex hormones and
      sexual function among 38 middle-aged obese men (BMI >or=35 kg/m(2)). RESEARCH
      METHODS AND PROCEDURES: A randomized controlled clinical trial was conducted. The
      treatment group (n = 19) participated in a 4-month weight-loss program including
      10 weeks on a very-low-energy diet (VLED) and 17 behavior modification visits.
      There was no intervention in the control group (n = 19). Both groups were
      followed for 8 months, i.e., 22 weeks after the active weight loss in the
      treatment group. The outcome measures (weight, sex hormones, sexual function,
      leptin, and metabolic variables) were obtained at baseline and at three time
      points during follow-up. RESULTS: The mean weight loss in the treatment group was
      21 kg at the end of the 10-week VLED. At the end of follow-up, the maintained
      weight loss was 17 kg of baseline weight. The control group was weight stable
      throughout the study. In the treatment group, increases in sex hormone-binding
      globulin, testosterone, and high-density lipoprotein-cholesterol, as well as
      decreases in insulin and leptin, were maintained until the end of follow-up,
      although with VLED, the level of several hormones and metabolic variables
      improved transiently during the rapid weight loss. There were no significant
      changes in the questionnaire scores on sexual function in either group.
      DISCUSSION: We conclude that obese men lose weight and increase their serum
      testosterone level on a weight-loss program with VLED and behavior modification.
      However, they do not change their sexual function scores.

PMID- 12805390
TI  - Effect of gastric banding on aminoterminal pro-brain natriuretic peptide in the
      morbidly obese.
AB  - OBJECTIVE: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain
      natriuretic peptide, might have diagnostic utility in detecting left ventricular
      hypertrophy and/or left ventricular dysfunction. The aim of the study was to
      investigate the relationship between morbid obesity and NT-proBNP and the effect
      of weight reduction on this parameter. RESEARCH METHODS AND PROCEDURES: A total
      of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding
      (LAGB). NT-proBNP levels were measured before and 12 months after the surgery.
      RESULTS: Metabolic features and systolic and diastolic blood pressure were
      significantly decreased (p < 0.00001 for both) after a cumulative weight loss of
      19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in
      morbidly obese patients before LAGB than in normal-weight control subjects
      (341.15 +/- 127.78 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p < 0.00001). After
      bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 +/
      127.78 fmol/mL to 204.87 +/- 59.84 fmol/mL (p < 0.00001) and remained
      statistically significantly elevated (204.88 +/- 59.84 fmol/mL vs. 161.68 +/-
      75.78 fmol/mL; p = 0.04) compared with normal-weight subjects. DISCUSSION: This
      investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects
      and a significant decrease during weight loss after laparoscopic adjustable
      gastric banding. In obesity, NT-proBNP might be useful as a routine screening
      method for identifying left ventricular hypertrophy and/or left ventricular
      dysfunction.

PMID- 12805391
TI  - High expression of complement components in omental adipose tissue in obese men.
AB  - OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity
      related metabolic disturbances. Factors that are predominantly expressed in this
      depot could mediate the link between visceral obesity and associated diseases.
      RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue
      biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA
      microarrays in triplicate and by real-time polymerase chain reaction. Serum C3
      and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing
      a cross section of the general population. Body composition was measured by
      computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and
      Factor B had higher expression in omental compared with subcutaneous adipose
      tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition,
      adipsin, which belongs to the alternative pathway, and the classical pathway
      components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue
      distribution showed high expression of C2, C3, and C4 in omental adipose tissue,
      and only liver had higher expression of these genes. Serum C3 levels correlated
      with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p <
      0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023
      and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only
      visceral fat in men (r = 0.36, p = 0.015) and with both depots in women
      (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001).
      DISCUSSION: Recent studies show that the metabolic syndrome is associated with
      chronically elevated levels of several immune markers, some of which may have
      metabolic effects. The high expression of complement genes in intra-abdominal
      adipose tissue might suggest that the complement system is involved in the
      development of visceral adiposity and/or contributes to the metabolic
      complications associated with increased visceral fat mass.

PMID- 12805392
TI  - Fasting plasma insulin modulates lipid levels and particle sizes in 2- to 3-year
      old children.
AB  - OBJECTIVE: Obesity and hyperinsulinemia are associated with dyslipidemia in
      adults and older children, but little is known about these relationships in very
      young children. We examined the relation of fasting insulin to lipid levels and
      lipid particle size in young healthy children. RESEARCH METHODS AND PROCEDURES:
      Analyses were performed on data from 491 healthy 2- and 3-year old Hispanic
      children enrolled in a dietary study conducted in New York City, 1992-1995.
      Obesity measures included BMI, ponderal index, skinfold thickness, and waist
      circumference. Low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)
      cholesterol particle size were measured by nuclear magnetic resonance. RESULTS:
      Fasting insulin level was positively correlated with triglyceride levels (r =
      0.24 for boys and r = 0.23 for girls; p < 0.001 for both) and inversely
      correlated with HDL-cholesterol level in boys (r = -0.20; p < 0.01). Higher
      fasting insulin level was also correlated with smaller mean HDL particle size in
      both boys (r = -0.21; p < 0.001) and girls (r = -0.14; p < 0.05) and smaller mean
      LDL particle size in boys (r = -0.13; p < 0.05). The associations of fasting
      insulin level with triglyceride and HDL-cholesterol levels and HDL and LDL
      particle size remained significant after multivariate regression adjustment for
      age, sex, and BMI or ponderal index. DISCUSSION: Fasting insulin level is
      associated with relative dyslipidemia in healthy 2- and 3-year-old Hispanic
      children.

PMID- 12805393
TI  - A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for
      weight loss in obesity.
AB  - OBJECTIVE: To evaluate the efficacy and safety of topiramate (TPM) for weight
      loss in healthy obese subjects. RESEARCH METHODS AND PROCEDURES: A randomized,
      double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred
      eighty-five subjects, 18 and 75 years of age, were randomized to receive either
      placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily.
      In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was
      raised every week by 32 mg/d (16 mg twice daily) until subjects reached their
      target dose. Twenty-four weeks after beginning treatment, all subjects were
      tapered off treatment by a dose reduction of 50% per week. All participants
      received the same lifestyle program. RESULTS: Mean percent weight loss from
      baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, 
      6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively.
      Greater percentages of TPM-treated patients lost at least 5% or 10% of body
      weight compared with placebo. The most frequent adverse events were related to
      the central or peripheral nervous system, including paresthesia, somnolence, and
      difficulty with memory, concentration, and attention. Most events were dose
      related, occurred early in treatment, and usually resolved spontaneously; only
      21% receiving TPM withdrew due to adverse events compared with 11% on placebo.
      DISCUSSION: TPM produced significantly greater weight loss than placebo at all
      doses.

PMID- 12805394
TI  - Medium-chain oil reduces fat mass and down-regulates expression of adipogenic
      genes in rats.
AB  - OBJECTIVE: To test the hypothesis that adipose tissue could be one of the primary
      targets through which medium-chain fatty acids (MCFAs) exert their metabolic
      influence. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed a
      control high-fat diet compared with an isocaloric diet rich in medium-chain
      triglycerides (MCTs). We determined the effects of MCTs on body fat mass, plasma
      leptin and lipid levels, acyl chain composition of adipose triglycerides and
      phospholipids, adipose tissue lipoprotein lipase activity, and the expression of
      key adipogenic genes. Tissue triglyceride content was measured in heart and
      gastrocnemius muscle, and whole body insulin sensitivity and glucose tolerance
      were also measured. The effects of MCFAs on lipoprotein lipase activity and
      adipogenic gene expression were also assessed in vitro using cultured adipose
      tissue explants or 3T3-L1 adipocytes. RESULTS: MCT-fed animals had smaller fat
      pads, and they contained a considerable amount of MCFAs in both triglycerides and
      phospholipids. A number of key adipogenic genes were down-regulated, including
      peroxisome proliferator activated receptor gamma and CCAAT/enhancer binding
      protein alpha and their downstream metabolic target genes. We also found reduced
      adipose tissue lipoprotein lipase activity and improved insulin sensitivity and
      glucose tolerance in MCT-fed animals. Analogous effects of MCFAs on adipogenic
      genes were found in cultured rat adipose tissue explants and 3T3-L1 adipocytes.
      DISCUSSION: These results suggest that direct inhibitory effects of MCFAs on
      adiposity may play an important role in the regulation of body fat development.

PMID- 12805395
TI  - Impaired pressure natriuresis in obese youths.
AB  - OBJECTIVE: To compare the response and recovery of blood pressure (BP) and sodium
      excretion (U(Na)V) in response to a behavioral stressor in overweight/obese and
      lean adolescents. RESEARCH METHODS AND PROCEDURES: Twenty-five lean (12% to 20%
      body fat) and 59 overweight/obese (>25% body fat) normotensive adolescents were
      provided all meals for 3 days (average sodium intake, 4000 +/- 200 mg/d), before
      performing the stressor on the third day. There was a 2-hour pre-stress rest,
      followed by a 1-hour stress (involving a video game task), and a 2-hour recovery.
      Percentage of body fat was obtained from DXA. U(Na)V was measured hourly, whereas
      systolic BP and diastolic BP measurements were obtained at 15-minute intervals,
      and averaged for each 1-hour period. RESULTS: There was no significant difference
      between the lean and overweight/obese group for the response of systolic BP and
      diastolic BP (group by time interaction, p = 0.60 and p = 0.64, respectively).
      However, the lean group had a significantly greater increase in U(Na)V in
      response to the stressor compared with the overweight/obese group (p = 0.02).
      U(Na)V remained elevated compared with baseline in both groups at the 1-hour (p
      <or= 0.0001) and 2-hour (p <or= 0.0001) post-time points. Furthermore, there was
      a tendency for a larger number of sodium retainers in the overweight/obese group
      compared with the lean group (39.0% vs. 20.0%; chi(2) = 2.85, df = 1, p = 0.09).
      DISCUSSION: This study provided evidence that sodium regulation was impaired
      during a behavioral stress in overweight/obese individuals compared with lean
      individuals.

PMID- 12805396
TI  - Comparison of methods for achieving 24-hour energy balance in a whole-room
      indirect calorimeter.
AB  - OBJECTIVE: To evaluate and compare methods for achieving 24-hour energy balance
      in a whole-room indirect calorimeter. RESEARCH METHODS AND PROCEDURES: Twenty
      four-hour energy expenditure (EE) for 34 healthy adults (16 women, 18 men) was
      measured in a calorimeter during a prestudy day and on a subsequent
      nonconsecutive assessment day (AD). Several methods for estimating EE on the AD
      using activity factors or regression equations with data available before the AD
      [anthropometrics, body composition, resting metabolic rate (RMR), sleeping
      metabolic rate (SMR) on prestudy day, 24-hour EE on prestudy day] were compared
      for predictive accuracy. RESULTS: Use of a 24-hour calorimeter stay gave the
      smallest mean absolute error (119 +/- 16 kcal/d) and smallest single maximum
      error (361 kcal/d). However, several other methods were only slightly, and not
      significantly, less accurate (e.g., mean absolute error = 131 +/- 17, 140 +/- 20,
      and 141 +/- 22 kcal/d and greatest error = 384, 370, and 593 kcal/d for
      anthropometric, RMR, and SMR regression equations, respectively). Fat-free mass
      alone and SMR with a simple activity factor were seen to be less accurate.
      DISCUSSION: Our results indicate that there may be some improvement in achieving
      24-hour energy balance in a metabolic chamber by using a preceding 24-hour
      calorimeter stay; that only slightly less accurate predictions can be obtained
      using a combination of anthropometric, body composition, and/or RMR measurements;
      and that there is little or no advantage in using SMR from a previous overnight
      calorimeter stay.

PMID- 12805397
TI  - Soluble leptin receptor and soluble receptor-bound fraction of leptin in the
      metabolic syndrome.
AB  - OBJECTIVE: In obesity, plasma leptin is high and soluble leptin receptor (sOb-R)
      levels are low, resulting in a low fraction of bound leptin. The aim of this
      study was to investigate the influence of insulin resistance (IR) and the
      metabolic syndrome (MS) on sOb-R concentration and the bound-free ratio of
      leptin. RESEARCH METHODS AND PROCEDURES: sOb-R, leptin levels, and homeostasis
      model assessment (HOMA) index for IR were determined in 76 middle-aged obese or
      overweight men. RESULTS: Concentration of sOb-R and soluble receptor-bound
      fraction of leptin were lowest in the highest tertile of HOMA-IR. sOb-R and the
      bound-free ratio of leptin correlated with HOMA-IR, leptin concentration, and
      waist-to-hip ratio independently of age, BMI, and fat mass. Leptin and waist-to
      hip ratio were the sole independent determinants of sOb-R concentration, and BMI,
      HOMA-IR, and visceral adipose tissue were independent determinants of the bound
      fractin of leptin. sOb-R concentration and the bound fraction of leptin decreased
      with increasing numbers of components of the MS, resulting in lower sOb-R
      concentration and a lower fraction of bound leptin in men with the MS.
      DISCUSSION: IR and abdominal obesity are associated with low sOb-R concentration
      and low bound-free ratio of leptin independent of fat mass. Low sOb-R
      concentration and low bound-free ratio of leptin segregate with components of the
      MS. We suggest that low sOb-R levels and a low fraction of specifically bound
      leptin are markers of leptin resistance, which is independently associated with
      IR and abdominal obesity and may constitute an additional component of the MS.

PMID- 12805398
TI  - Nosocomial infections and obesity in surgical patients.
AB  - OBJECTIVE: There is an increased morbidity and mortality associated with surgery
      in the obese patient. This study was conducted to determine risk factors and
      compare the nosocomial infection rate in obese and nonobese surgical patients.
      RESEARCH METHODS AND PROCEDURES: A total of 395 surgical patients were evaluated.
      BMI was calculated for each patient. Various conventional risk factors for
      nosocomial infections were recorded. Biochemical parameters with plasma total
      cholesterol and high-density lipoprotein-cholesterol levels were measured. The
      diagnosis of infection was made according to the Centers for Disease Control and
      Prevention criteria. Univariate and two-step multivariate logistic regression
      methods were used for determination of nosocomial infection risk factors.
      RESULTS: There were 117 nosocomial infections identified in 96 of 395 surgically
      operated patients. A significant increase in the total number of nosocomial
      infections was determined in obese patients compared with the normal-weight
      patients (p < 0.05). High-density lipoprotein-cholesterol below the 10th
      percentile increased risk of surgical site infection. DISCUSSION: Our results
      suggest that obesity is an important risk factor for postoperative nosocomial
      infection.

PMID- 12805399
TI  - High serum leptin is associated with attenuated coronary vasoreactivity.
AB  - OBJECTIVE: Hyperleptinemia, a hallmark of obesity, appears to be a risk factor
      for coronary artery disease. However, although leptin is a vasoactive hormone, no
      studies addressing leptin's effect on coronary perfusion have been performed. We
      examined the association between circulating leptin concentration and coronary
      vasoreactivity in young obese and nonobese males. RESEARCH METHODS AND
      PROCEDURES: Myocardial blood flow was quantitated in 10 obese men (age 31 +/- 7
      years, BMI 34 +/- 2 kg/m(2)) and 10 healthy matched nonobese men (age 33 +/- 8
      years, BMI 24 +/- 2 kg/m(2)) using positron emission tomography and O-15-water.
      The measurements were performed basally and during adenosine infusion (140 micro
      g/kg per minute). RESULTS: Serum leptin was significantly higher in obese than
      nonobese subjects (10.3 +/- 5.6 vs. 4.3 +/- 2.5 ng/mL, p < 0.01). Basal
      myocardial blood flow was not significantly different between obese and nonobese
      subjects. Adenosine-stimulated flow was blunted in obese (3.2 +/- 0.6 mL/g per
      minute) when compared with nonobese subjects (4.0 +/- 1.1 mL/g per minute, p <
      0.05). Serum leptin concentration was inversely associated with adenosine
      stimulated flow in study subjects (r = -0.50, p < 0.05). This association was no
      longer observed after adjustment for obesity and/or hyperinsulinemia. DISCUSSION:
      Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young
      obese but otherwise healthy men. Moreover, the adenosine-stimulated myocardial
      flow is inversely related to prevailing concentration of serum leptin. Although
      this relationship appears to be explained by obesity and/or hyperinsulinemia,
      leptin might have a role in regulation of myocardial blood supply.

PMID- 12805400
TI  - Eating behaviors and indexes of body composition in men and women from the Quebec
      family study.
AB  - OBJECTIVE: To put into relationship the dietary and anthropometric profile of men
      and women with their eating behaviors (cognitive dietary restraint,
      disinhibition, and susceptibility to hunger) and to assess whether gender and
      obesity status influence these associations. RESEARCH METHODS AND PROCEDURES:
      Anthropometric measurements (including visceral adipose tissue accumulation),
      dietary profile (3-day food record), and eating behaviors (Three-Factor Eating
      Questionnaire) were determined in a sample of 244 men and 352 women. RESULTS:
      Women had significantly higher cognitive dietary restraint and disinhibition
      scores than men (p < 0.0001). In both genders, scores for disinhibition and
      susceptibility to hunger, but not for cognitive dietary restraint, were higher in
      obese subjects than in overweight and nonobese subjects (p < 0.05). Positive
      correlations were observed between rigid restraint and most of the anthropometric
      variables studied (0.12 <or= r <or= 0.16). Moreover, in women, flexible restraint
      was negatively associated with body fat and waist circumference (r = -0.11).
      Cognitive dietary restraint and rigid restraint were positively related to BMI
      among nonobese women (0.19 <or= r <or= 0.20), whereas in obese men, cognitive
      dietary restraint and flexible restraint tended to be negatively correlated with
      BMI (-0.20 <or= r <or= -0.22; p = 0.10). DISCUSSION: Gender could mediate
      associations observed between eating behaviors and anthropometric profile. It was
      also found that disinhibition and susceptibility to hunger are positively
      associated with the level of obesity. On the other hand, cognitive dietary
      restraint is not consistently related to body weight and adiposity, whereas rigid
      and flexible restraint are oppositely associated to obesity status, which
      suggests that it is important to differentiate the subscales of cognitive dietary
      restraint. Finally, counseling aimed at coping with disinhibition and
      susceptibility to hunger could be of benefit for the long-term treatment of
      obesity.

PMID- 12805401
TI  - Is the ArteACC index a valid indicator of free-living physical activity in
      adolescents?
AB  - OBJECTIVE: The principal aim of this study was to validate a proposed new index
      of physical activity, the activity-related time equivalent based on accelerometry
      (ArteACC), in adolescents. A secondary aim was to develop regression equations
      for prediction of total energy expenditure (TEE) and activity energy expenditure
      [AEE = 0.9 x TEE - resting metabolic rate (RMR)]. RESEARCH METHODS AND
      PROCEDURES: RMR and energy expenditure (EE) under standardized exercises were
      measured by indirect calorimetry in 36 adolescents (14 to 19 years old). TEE was
      measured by the doubly labeled water method, and physical activity was assessed
      simultaneously with an accelerometer for 14 days. AEE, AEE in relation to body
      weight (AEE per kilogram), and activity-related time equivalent based on energy
      expenditure (ArteEE = AEE/[EE reference activity - RMR]) were calculated from
      laboratory and free-living EE data. ArteACC was calculated as total activity
      counts/activity counts of reference activity. RESULTS: ArteACC was significantly
      related to AEE per kilogram (r = 0.57; p < 0.0001) and ArteEE (r = 0.68; p <
      0.001). The absolute amount of time (minutes per day) spent in physical activity
      was significantly lower when calculated from ArteACC than from ArteEE (p <
      0.001). TEE was significantly influenced by RMR, sex, and ArteACC (r(2) = 0.89).
      AEE was significantly influenced by sex and ArteACC (r(2) = 0.59). DISCUSSION:
      Despite an absolute difference between the two indexes, ArteEE and ArteACC,
      ArteACC seems to be a valid indicator of free-living physical activity. It
      contributed significantly, by 3.3% and 12.5%, to the explained variations in TEE
      and AEE, respectively.

PMID- 12805402
TI  - Association of obesity, but not diabetes or hypertension, with glucocorticoid
      receptor N363S variant.
AB  - OBJECTIVE: To determine whether the N363S variant in the glucocorticoid receptor
      (encoded by nuclear receptor subfamily 3, group C, member 1: NR3C1) is associated
      with obesity, type 2 diabetes, or hypertension. RESEARCH METHODS AND PROCEDURES:
      This was a cross-sectional case-control study involving 951 Anglo-Celtic/Northern
      European subjects from Sydney. This study consisted of the following: 1) an
      obesity clinic group, most of whom had "morbid obesity" (mean BMI for group = 43
      +/- 8 kg/m(2); n = 152); 2) a type 2 diabetes clinic group (n = 356); 3) patients
      with essential hypertension who had a strong family history (n = 141); and 4)
      normal healthy controls (n = 302). N363S genotype, BMI, and a range of other
      parameters relevant to each group were measured. RESULTS: Compared with the
      frequency of 0.04 in nonobese healthy subjects, the S363 allele was significantly
      higher in obesity clinic patients (0.17; p = 5.6 x 10(-8)), subjects with
      diabetes who were also obese (0.09; p = 0.0045), subjects with hypertension who
      were also overweight (0.08; p = 0.0016), and overweight healthy subjects (0.12; p
      = 0.0004). DISCUSSION: The NR3C1 N363S variant is associated with obesity and
      overweight in a range of patient settings but is not associated with hypertension
      or type 2 diabetes.

PMID- 12805403
TI  - Amyloid endostatin induces endothelial cell detachment by stimulation of the
      plasminogen activation system.
AB  - Endostatin is a fragment of collagen XVIII that acts as an inhibitor of tumor
      angiogenesis and tumor growth. Anti-tumor effects have been described using both
      soluble and insoluble recombinant endostatin. However, differences in endostatin
      structure are likely to cause differences in bioactivity. In the present study,
      we have investigated the cellular effects of insoluble endostatin. We previously
      found that insoluble endostatin shows all the hallmarks of amyloid aggregates and
      potently stimulates tissue plasminogen activator-mediated formation of the serine
      protease plasmin. We here show that amyloid endostatin induces plasminogen
      activation by endothelial cells, resulting in vitronectin degradation and plasmin
      dependent endothelial cell detachment. Endostatin-mediated stimulation of
      plasminogen activation, vitronectin degradation, and endothelial cell detachment
      is inhibited by carboxypeptidase B, indicating an essential role for carboxyl
      terminal lysines. Our results suggest that amyloid endostatin may inhibit
      angiogenesis and tumor growth by stimulating the fibrinolytic system.

PMID- 12805404
TI  - Epigenetic regulation of proprotein convertase PACE4 gene expression in human
      ovarian cancer cells.
AB  - Proprotein convertases (PC) are a family of serine endoproteases that play
      important roles in regulating cell function by converting proproteins to
      biologically active molecules. Several lines of evidence suggest that
      overexpression of PCs contributes to tumor formation and progression in various
      types of cancer. In this study, we examined PC expression in six normal ovarian
      surface epithelium (OSE) cultures, nine primary ovarian cancer (OC) cultures, and
      three established OC cell lines (Hey, HeyC2, and OCC-1). Our results show that
      furin and PC7 expression in OC cells was comparable to that in normal OSE.
      However, PACE4 expression was greatly reduced in all OC samples studied. PACE4
      promoter activity was measured in HeyC2 and OCC-1 cells using transiently
      transfected luciferase reporter plasmids. Both cell lines supported PACE4
      promoter activity, showing that the transcription factors critical for PACE4
      expression are present in OC cells. The observation that established OC cell
      lines have reduced PACE4 expression, but maintained the ability to support PACE4
      promoter activity, led to the hypothesis that reduced expression may be due to
      epigenetic modification of the PACE4 gene, such as DNA methylation and histone
      deacetylation. Methylation analysis of 79 CpG dinucleotides within the PACE4
      promoter and exon I (-196/+340) revealed that the percentage of methylated
      cytosine nucleotides was 8-9% in normal OSE, but 58-93% in OC cells. Treatment
      with the demethylating agent 5-aza-2'-deoxycytidine and/or the histone
      deacetylase inhibitor trichostatin A greatly increased PACE4 expression in OC
      cells. These data suggest that the reduction of PACE4 expression in OC cells is
      caused, in part, by DNA hypermethylation and histone deacetylation.

PMID- 12805405
TI  - Ectopic expression of 10-formyltetrahydrofolate dehydrogenase in A549 cells
      induces G1 cell cycle arrest and apoptosis.
AB  - We have recently shown that transient expression of 10-formyltetrahydrofolate
      dehydrogenase (FDH) strongly inhibits proliferation of several cancer cell lines
      and ultimately results in cell death. In the present studies using Tet-On system,
      we have generated a stable A549 lung carcinoma cell line capable of inducible FDH
      expression. Using this system, we were able to express FDH at different levels
      depending on concentration of the inducer, doxycycline, and we have observed that
      inhibition of proliferation depends on FDH intracellular levels. We have further
      shown that induction of FDH expression results in initiation of apoptosis
      beginning 24 h post-induction. Apoptotic cells revealed cleavage of poly-(ADP
      ribose) polymerase and general caspase inhibitor zVAD-fmk protected cells against
      FDH-induced apoptosis. FDH-expressing cells showed accumulation of cells in G(0)
      G(1) phase and a sharp decrease of cells in S phase. Accumulation of
      intracellular FDH was followed by accumulation of the tumor suppressor protein
      p53 and its downstream target p21. These results indicate that FDH
      antiproliferative effects on A549 cells include both G(1) cell cycle arrest and
      caspase-dependent apoptosis.

PMID- 12805406
TI  - The C-terminal seven amino acids in the cytoplasmic retention signal region of
      cyclin B2 are required for normal bipolar spindle formation in Xenopus oocytes
      and embryos.
AB  - In many vertebrates, cyclin B has several subtypes, but the functional
      differences among them are largely unclear. Previously, we have shown that
      Xenopus cyclin B2, not cyclin B1, is involved in bipolar spindle formation
      through its cytoplasmic retention signal (CRS) region. However, identification of
      a nuclear export signal (NES) in the CRS region of cyclin B1 raised the
      possibility that an NES-like sequence (NELS) present in the CRS region of cyclin
      B2 might be involved in bipolar spindle formation. We show here that cyclin B2 is
      actually exported from the nucleus via its NELS, but that overexpression of the
      cyclin B2 CRS region, having a mutated NELS, still inhibits bipolar spindle
      formation in oocytes. In contrast, overexpression of the cyclin B2 CRS region
      lacking its C-terminal seven amino acids no longer inhibits bipolar spindle
      formation in oocytes or embryos. These results suggest strongly that the CRS
      region, especially its C-terminal seven acidic residues, of cyclin B2 is required
      for bipolar spindle formation in both the meiotic and mitotic cell divisions.

PMID- 12805407
TI  - Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans
      phosphorylation.
AB  - Chk2 is a serine/threonine protein kinase found mutated in certain hereditary and
      sporadic cancers. Ionizing radiation (IR) activates the kinase activity of Chk2
      in a phosphorylation-dependent manner. ATM phosphorylates Chk2 on threonine 68,
      which promotes oligomerization and phosphorylation on threonines 383 and 387
      within the activation loop of the catalytic domain. In this study, threonines 68,
      383, and 387 were confirmed as sites of Chk2 phosphorylation both in vitro and in
      vivo. In addition, serine 516 was identified as a novel IR-inducible
      phosphorylation site in vivo and as a site of autophosphorylation in vitro.
      Interestingly, Chk2 was capable of autoactivation in the absence of IR when
      overproduced in bacteria, in 293 cells, and in murine embryonic fibroblasts
      lacking Chk2. A kinase-inactive mutant of Chk2 was phosphorylated on T68 and
      T383/T387 but not on S516 in cells containing Chk2 and on T68 but not T383/T387
      or S516 in cells lacking Chk2. This establishes a dependency on Chk2 kinase
      activity for phosphorylation of T383/T387 and S516 but not for T68 in vivo. We
      demonstrate that T68 phosphorylation is regulated by kinases in addition to ATM
      and Chk2. Taken together, our data indicate that autophosphorylation of Chk2 can
      occur both in cis and in trans and suggest that oligomerization may regulate Chk2
      activation by promoting these cis- and trans-phosphorylation events. The
      importance of oligomerization is underscored by the observation that substitution
      of isoleucine for threonine at position 157, a mutation found in a subset of
      patients with Li-Fraumeni syndrome, impairs both Chk2 oligomerization and
      autophosphorylation.

PMID- 12805408
TI  - Cell type-dependent regulation of hMLH1 promoter activity is influenced by the
      presence of multiple redundant elements.
AB  - Immunohistochemical analysis confirmed the presence of MLH1 protein in A2780
      ovarian cancer cells and its absence in this same cell line on acquired
      resistance to cisplatinum (A2780/CP). Transfection of a -1781-bp hMLH1 promoter
      construct into either A2780 or A2780/CP cells produced similar (30-fold)
      induction of luciferase, an indication that the transcriptional machinery for
      hMLH1 expression remains intact. hMLH1-luciferase activity was also unaffected by
      re-expression of hMLH1 following treatment of A2780/CP cells with the methylase
      inhibitor 2'-deoxy-5-azacytidine. Serial 5'-deletion studies of the hMLH1
      promoter region in ovarian cancer cells localized transcriptional enhancers to a
      region (-250 to -151 bp) that excludes the previously identified CCAAT element (
      282) active in HeLa cells. When these same deletion constructs were transfected
      into HeLa cells, deletion of the CCAAT-containing region caused a significant
      loss of promoter activity, an indication of cell-specific use of enhancer
      elements. Finally, a series of internal deletion and linker mutation studies of
      the -250 to -151 bp ovarian enhancer region revealed that the hMLH1 promoter
      contains multiple redundant enhancer elements capable of independent promoter
      activation and may explain the association of this region with methylation
      silencing of hMLH1.

PMID- 12805409
TI  - Identification and characterization of retinoic acid receptor beta2 target genes
      in F9 teratocarcinoma cells.
AB  - Retinoids, a group of natural and synthetic analogues of vitamin A (retinol),
      modulate the differentiation of many cell types. Retinoids are also used for the
      prevention and treatment of cancer. The actions of retinoids are generally
      mediated by the retinoic acid receptors (RARs alpha, beta, and gamma) and the
      retinoid X receptors (RXRs alpha, beta, and gamma). One of the RARs, RARbeta, is
      expressed at reduced levels in many human carcinomas, and F9 RARbeta(2)(-/-)
      cells do not growth arrest in response to RA. To determine if RARbeta(2)
      regulates the expression of a unique set of genes, through the use of subtractive
      hybridization and DNA array analysis, we have identified and characterized genes
      that are differentially expressed in F9 RARbeta(2)(-/-) teratocarcinoma cells.
      These genes, which encode transcription factors, cell surface signal transduction
      molecules, and metabolic enzymes, include c-myc, FOG1, GATA6, glutamate
      dehydrogenase, glutathione S-transferase homologue (p28), Foxq1, Hic5, Meis1a,
      Dab2, midkine, and the PDGF-alpha receptor. These genes are regulated
      specifically by RARbeta(2) in F9 wild-type (Wt) cells as indicated by their
      expression profiles in F9 RARbeta(2)(-/-) cells as compared to F9 Wt, RARalpha(-/
      ), or RARgamma(-/-) cells, and their responsiveness to specific retinoid receptor
      agonists. The basal expression levels of some of these genes, such as c-myc, are
      higher in the F9 RARbeta(2)(-/-) cells than in F9 Wt in the absence of exogenous
      retinoids, suggesting that RARbeta(2) can inhibit gene expression in the absence
      of a ligand. The RARbeta(2) target genes are transcriptionally activated by
      retinol, as well as RA, in F9 Wt cells. Because the lack of RARbeta(2) alters
      both the control of proliferation and differentiation in F9 cells, the genes that
      we have characterized may mediate key effects of RA, via RARbeta(2), on these
      processes.

PMID- 12805410
TI  - The small heterodimer partner interacts with the pregnane X receptor and
      represses its transcriptional activity.
AB  - SHP (small heterodimer partner, NR1I0) is an atypical orphan member of the
      nuclear receptor subfamily in that it lacks a DNA-binding domain. It is mostly
      expressed in the liver, where it binds to and inhibits the function of nuclear
      receptors. SHP is up-regulated by primary bile acids, through the activation of
      their receptor farnesoid X receptor, leading to the repression of cholesterol
      7alpha-hydroxylase (CYP7alpha) expression, the rate-limiting enzyme in bile acid
      production from cholesterol. PXR (pregnane X receptor, NR1I2) is a broad
      specificity sensor that recognizes a wide variety of synthetic drugs as well as
      endogenous compounds such as bile acid precursors. Upon activation, PXR induces
      CYP3A and inhibits CYP7alpha, suggesting that PXR can act on both bile acid
      synthesis and elimination. Indeed, CYP7alpha and CYP3A are involved in
      biochemical pathways leading to cholesterol conversion into primary bile acids,
      whereas CYP3A is also involved in the detoxification of toxic secondary bile acid
      derivatives. Here, we show that PXR is a target for SHP. Using pull-down assays,
      we show that SHP interacts with both murine and human PXR in a ligand-dependent
      manner. From transient transfection assays, SHP is shown to be a potent repressor
      of PXR transactivation. Furthermore, we report that chenodeoxycholic acid and
      cholic acid, two farnesoid X receptor ligands, induce up-regulation of SHP and
      provoke a repression of PXR-mediated CYP3A induction in human hepatocytes as well
      as in vivo in mice. These results reveal an elaborate regulatory cascade, tightly
      controlled by SHP, for both the maintenance of bile acid production and
      detoxification in the liver.

PMID- 12805411
TI  - Thyrotropin-releasing hormone receptor processing: role of ubiquitination and
      proteasomal degradation.
AB  - These studies were designed to characterize ubiquitination of the G protein
      coupled TRH receptor (TRHR). TRHRs and ubiquitin coprecipitated with antibodies
      to either receptor or ubiquitin in Chinese hamster ovary or pituitary GHFT cells.
      Inhibition of the proteasome with MG-132 resulted in an accumulation of total
      TRHRs and the appearance of a small amount of cytosolic receptor. MG-132 caused
      an increase in newly synthesized receptors, detected by microscopy using a TRHR
      coupled to Timer, a DsRed that undergoes a spontaneous time-dependent color
      change. Misfolded TRHRs were particularly heavily ubiquitinated. These results
      show that the proteasome participates in TRHR quality control early after
      receptor synthesis. Under normal circumstances, most ubiquitinated TRHRs were
      absorbed to wheat germ agglutinin, indicating that they had undergone complex
      glycosylation in the Golgi apparatus. When cells were treated with tunicamycin to
      block glycosylation, a ladder of ubiquitinated species was detectable. Cell
      surface receptors, which were labeled selectively with either radioligand or
      antibody, showed no detectable ubiquitin modification. To determine if
      ubiqutination plays a role in TRH-induced receptor endocytosis, the receptor was
      expressed in Ts20 cells, which have a temperature-sensitive ubiquitin pathway.
      TRH induced a significant calcium response and rapid and extensive receptor
      internalization at both the permissive and nonpermissive temperatures, indicating
      that ligand-dependent ubiquitination of the receptor, or any other protein, is
      not necessary for TRHR signaling or internalization. These results show that
      ubiquitin modification targets misfolded receptors for degradation and suggest a
      possible role for ubiquitination in receptor trafficking.

PMID- 12805412
TI  - Review of the in vivo functions of the p160 steroid receptor coactivator family.
AB  - The p160 steroid receptor coactivator (SRC) gene family contains three homologous
      members, which serve as transcriptional coactivators for nuclear receptors and
      certain other transcription factors. These coactivators interact with ligand
      bound nuclear receptors to recruit histone acetyltransferases and
      methyltransferases to specific enhancer/promotor regions, which facilitates
      chromatin remodeling, assembly of general transcription factors, and
      transcription of target genes. This minireview summarizes our current knowledge
      about the molecular structures, molecular mechanisms, temporal and spatial
      expression patterns, and biological functions of the SRC family. In particular,
      this article highlights the roles of SRC-1 (NCoA-1), SRC-2 (GRIP1, TIF2, or NCoA
      2) and SRC-3 (p/CIP, RAC3, ACTR, AIB1, or TRAM-1) in development, organ function,
      endocrine regulation, and nuclear receptor function, which are defined by
      characterization of the genetically manipulated animal models. Furthermore, this
      article also reviews our current understanding of the role of SRC-3 in breast
      cancer and discusses possible mechanisms for functional specificity and
      redundancy among SRC family members.

PMID- 12805413
TI  - Thyroid hormone activates fibroblast growth factor receptor-1 in bone.
AB  - Thyroid hormone (T3) and the T3 receptor (TR) alpha gene are essential for bone
      development whereas adult hyperthyroidism increases the risk of osteoporotic
      fracture. We isolated fibroblast growth factor receptor-1 (FGFR1) as a T3-target
      gene in osteoblasts by subtraction hybridization. FGFR1 mRNA was induced 2- to 3
      fold in osteoblasts treated with T3 for 6-48 h, and FGFR1 protein was stimulated
      2- to 4-fold. Induction of FGFR1 was independent of mRNA half-life and abolished
      by actinomycin D and cycloheximide, indicating the involvement of an intermediary
      protein. Fibroblast growth factor 2 (FGF2) stimulated MAPK in osteoblasts, and
      pretreatment with T3 for 6 h induced a more rapid response to FGF that was
      increased in magnitude by 2- to 3-fold. Similarly, T3 enhanced FGF2-activated
      autophosphorylation of FGFR1, but did not modify FGF2-induced phosphorylation of
      the docking protein FRS2. These effects were abolished by the FGFR-selective
      inhibitors PD166866 and PD161570. In situ hybridization analyses of TRalpha
      knockout mice, which have impaired ossification and skeletal mineralization,
      revealed reduced FGFR1 mRNA expression in osteoblasts and osteocytes, whereas T3
      failed to stimulate FGFR1 mRNA or enhance FGF2-activated MAPK signaling in
      TRalpha-null osteoblasts. These findings implicate FGFR1 signaling in T3
      dependent bone development and the pathogenesis of skeletal disorders resulting
      from thyroid disease.

PMID- 12805414
TI  - Nucleic acid-based immune system: the antiviral potential of mammalian RNA
      silencing.

PMID- 12805415
TI  - Hepatitis B virus core protein stimulates the proteasome-mediated degradation of
      viral X protein.
AB  - Hepatitis B virus (HBV) X protein (HBx) plays an essential role in viral
      replication and in the development of hepatocellular carcinoma. HBx has the
      ability to transactivate the expression of all HBV proteins, including the viral
      core protein HBc. Consistent with its regulatory role, HBx is relatively unstable
      and is present at low levels in the cell. We report here that the level of HBx
      was significantly reduced by the coexpression of HBc in cultured human hepatoma
      cells, whereas the level of HBx mRNA was unaffected. The repression of HBx by HBc
      was relieved by treating cells with the proteasome inhibitor MG132, indicating
      that HBc acts by stimulating the proteasome-mediated degradation of HBx.
      Moreover, the inhibitory effect of HBc was specific to HBx and did not affect
      other proteins, including p53, a known target of the proteasome. Although no
      direct physical interaction between HBc and HBx could be demonstrated, mutational
      analysis indicated that the C-terminal half of HBc is responsible for its
      inhibitory effect. These results suggest that HBc functions as a novel regulator
      of the HBV life cycle and of hepatocellular carcinogenesis through control of the
      HBx level via an inhibitory feedback type of mechanism.

PMID- 12805416
TI  - Sustained small interfering RNA-mediated human immunodeficiency virus type 1
      inhibition in primary macrophages.
AB  - Small interfering RNAs (siRNAs) can induce potent gene silencing by degradation
      of cognate mRNA. However, in dividing cells, the silencing lasts only 3 to 7
      days, presumably because of siRNA dilution with cell division. Here, we
      investigated if sustained siRNA-mediated silencing of human immunodeficiency
      virus type 1 (HIV-1) is possible in terminally differentiated macrophages, which
      constitute an important reservoir of HIV in vivo. CCR5, the major HIV-1
      coreceptor in macrophages, and the viral structural gene for p24 were targeted
      either singly or in combination. When transfected 2 days prior to infection, both
      CCR5 and p24 siRNAs effectively reduced HIV-1 infection for the entire 15-day
      period of observation, and combined targeting of both genes abolished infection.
      To investigate whether exogenously introduced siRNA is maintained stably in
      macrophages, we tested the kinetics of siRNA-mediated viral inhibition by
      initiating infections at various times (2 to 15 days) after transfection with
      CCR5 and p24 siRNAs. HIV suppression mediated by viral p24 siRNA progressively
      decreased and was lost by day 7 posttransfection. In contrast, viral inhibition
      by cellular CCR5 knockdown was sustained even when transfection preceded
      infection by 15 days, suggesting that the continued presence of target RNA may be
      needed for persistence of siRNA. The longer sustenance of CCR5 relative to p24
      siRNA in uninfected macrophages was also confirmed by detection of internalized
      siRNA by modified Northern blot analysis. We also tested the potential of p24
      siRNA to stably silence HIV in the setting of an established infection where the
      viral target gene is actively transcribed. Under these circumstances, long-term
      suppression of HIV replication could be achieved with p24 siRNA. Thus, siRNAs can
      induce potent and long-lasting HIV inhibition in nondividing cells such as
      macrophages.

PMID- 12805417
TI  - Murine cytomegalovirus abortively infects human dendritic cells, leading to
      expression and presentation of virally vectored genes.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that play a crucial role
      in antigen-specific immune responses. Thus, the targeting of exogenous antigens
      to DC has become a popular approach for cancer immunotherapy and vaccine
      development. In this report, we studied the interplay between murine
      cytomegalovirus (MCMV) and human monocyte-derived DC. The results showed that an
      enhanced green fluorescent protein (EGFP)-encoding, replication-competent MCMV
      vector underwent abortive infection in human DC; this was accompanied by the
      efficient expression of EGFP. Infection of human DC by this vector resulted in a
      modest increase in the expression of cell surface proteins associated with DC
      maturation and has no significant effect on the immunostimulatory function of the
      cells, as reflected by their ability to support T-cell proliferation in a mixed
      lymphocyte reaction. Finally, an MCMV vector encoding the human immunodeficiency
      virus type 1 (HIV-1) gp120 envelope glycoprotein was constructed and used to
      infect cultured human DC. The infected DC were shown to be capable of stimulating
      the expansion of autologous, gp120-specific, class I-restricted T lymphocytes
      from an HIV-1-negative donor, as determined by tetramer staining and enzyme
      linked immunospot analysis. Taken together, these results suggest that MCMV may
      have potential utility as a vector for human vaccine development.

PMID- 12805418
TI  - Effects of mutant ubiquitin on ts1 retrovirus-mediated neuropathology.
AB  - ts1 is a temperature-sensitive mutant of Moloney murine leukemia virus that
      induces a rapid spongiform encephalopathy in mice infected as newborns. The
      pathological features include the formation of ubiquitinated inclusions
      resembling Lewy bodies. To determine how perturbation of the ubiquitin-proteasome
      pathway might affect ts1-mediated neurodegeneration, the virus was introduced
      into transgenic mice in which the assembly of ubiquitin chains was compromised by
      the expression of dominant-negative mutant ubiquitin. The onset of symptoms was
      greatly delayed in a transgenic mouse line expressing K48R mutant ubiquitin; no
      such delay was observed in mice expressing a wild-type ubiquitin transgene or
      K63R mutant ubiquitin. The extended latency was found to correlate with a delayed
      increase in viral titers. Pathological findings in K48R transgenic mice at 60
      days were found to be similar to those in the other strains at 30 days,
      suggesting that while delayed, the neurodegenerative process in K48R mice was
      otherwise similar. These data demonstrate the sensitivity of retroviral
      replication to the partial disruption of ubiquitin-mediated proteolysis in vivo,
      a finding that may have therapeutic potential.

PMID- 12805419
TI  - Mosaic genomes of the six major primate lentivirus lineages revealed by
      phylogenetic analyses.
AB  - To clarify the origin and evolution of the primate lentiviruses (PLVs), which
      include human immunodeficiency virus types 1 and 2 as well as their simian
      relatives, simian immunodeficiency viruses (SIVs), isolated from several host
      species, we investigated the phylogenetic relationships among the six supposedly
      nonrecombinant PLV lineages for which the full genome sequences are available.
      Employing bootscanning as an exploratory tool, we located several regions in the
      PLV genome that seem to have uncertain or conflicting phylogenetic histories.
      Phylogeny reconstruction based on distance and maximum-likelihood algorithms
      followed by a number of statistical tests confirms the existence of at least five
      putative recombinant fragments in the PLV genome with different clustering
      patterns. Split decomposition analysis also shows that phylogenetic relationships
      among PLVs may be better represented by network-based graphs, such as the ones
      produced by SplitsTree. Our findings not only imply that the six so-called pure
      PLV lineages have in fact mosaic genomes but also make more unlikely the
      hypothesis of cospeciation of SIVs and their simian hosts.

PMID- 12805420
TI  - The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via
      a predicted basic amphipathic helix that disrupts mitochondrial function.
AB  - The 11th influenza A virus gene product is an 87-amino-acid protein provisionally
      named PB1-F2 (because it is encoded by an open reading frame overlapping the PB1
      open reading frame). A significant fraction of PB1-F2 localizes to the inner
      mitochondrial membrane in influenza A virus-infected cells. PB1-F2 appears to
      enhance virus-induced cell death in a cell type-dependent manner. For the present
      communication we have identified and characterized a region near the COOH
      terminus of PB1-F2 that is necessary and sufficient for its inner mitochondrial
      membrane localization, as determined by transient expression of chimeric proteins
      consisting of elements of PB1-F2 genetically fused to enhanced green fluorescent
      protein (EGFP) in HeLa cells. Targeting of EGFP to mitochondria by this sequence
      resulted in the loss of the inner mitochondrial membrane potential, leading to
      cell death. The mitochondrial targeting sequence (MTS) is predicted to form a
      positively charged amphipathic alpha-helix and, as such, is similar to the MTS of
      the p13(II) protein of human T-cell leukemia virus type 1. We formally
      demonstrate the functional interchangeability of the two sequences for
      mitochondrial localization of PB1-F2. Mutation analysis of the putative
      amphipathic helix in the PB1-F2 reveals that replacement of five basic amino
      acids with Ala abolishes mitochondrial targeting, whereas mutation of two highly
      conserved Leu to Ala does not. These findings demonstrate that PB1-F2 possesses
      an MTS similar to other viral proteins and that this MTS, when fused to EGFP, is
      capable of independently compromising mitochondrial function and cellular
      viability.

PMID- 12805421
TI  - Flexibility of the adenovirus fiber is required for efficient receptor
      interaction.
AB  - The adenovirus (Ad) fiber protein mediates Ad binding to the coxsackievirus and
      Ad receptor (CAR) and is thus a major determinant of viral tropism. The fiber
      contains three domains: an N-terminal tail that anchors the fiber to the viral
      capsid, a central shaft region of variable length and flexibility, and a C
      terminal knob domain that binds to cell receptors. Ad type 37 (Ad37), a subgroup
      D virus associated with severe ocular infections, is unable to use CAR
      efficiently to infect host cells, despite containing a CAR binding site in its
      fiber knob. We hypothesized that the relatively short, inflexible Ad37 fiber
      protein restricts interactions with CAR at the cell surface. To test this
      hypothesis, we analyzed the infectivity and binding of recombinant Ad particles
      containing modified Ad37 or Ad5 fiber proteins. Ad5 particles equipped with a
      truncated Ad5 fiber or with a chimeric fiber protein comprised of the Ad5 knob
      fused to the short, rigid Ad37 shaft domain had significantly reduced infectivity
      and attachment. In contrast, placing the Ad37 knob onto the long, flexible Ad5
      shaft allowed CAR-dependent virus infection and cell attachment, demonstrating
      the importance of the shaft domain in receptor usage. Increasing fiber rigidity
      by substituting the predicted flexibility modules in the Ad5 shaft with the
      corresponding regions of the rigid Ad37 fiber dramatically reduced both virus
      infection and cell attachment. Cryoelectron microscopy (cryo-EM) single-particle
      analysis demonstrated the increased rigidity of this chimeric fiber. These
      studies demonstrate that both length and flexibility of the fiber shaft regulate
      CAR interaction and provide a molecular explanation for the use of alternative
      receptors by subgroup D Ad with ocular tropism. We present a molecular model for
      Ad-CAR interactions at the cell surface that explains the significance of fiber
      flexibility in cell attachment.

PMID- 12805422
TI  - A nuclear kinesin-like protein interacts with and stimulates the activity of the
      leucine-rich nuclear export signal of the human immunodeficiency virus type 1 rev
      protein.
AB  - The Rev protein of human immunodeficiency virus type 1 (HIV-1) is essential for
      the nucleocytoplasmic transport of unspliced and partially spliced HIV mRNAs
      containing the Rev response element (RRE). In a yeast two-hybrid screen of a HeLa
      cell-derived cDNA expression library for human factors interacting with the Rev
      leucine-rich nuclear export sequence (NES), we identified a kinesin-like protein,
      REBP (Rev/Rex effector binding protein), highly homologous to Kid, the carboxy
      terminal 75-residue region of which interacts specifically with the NESs of HIV-1
      Rev, human T-cell leukemia virus type 1 Rex, and equine infectious anemia virus
      Rev but not with functionally inactive mutants thereof. REBP is a nuclear protein
      that colocalizes with Rev in the nucleoplasm and nuclear periphery of transfected
      cells. Specific, albeit weak, interaction between REBP and Rev could be
      demonstrated in coimmunoprecipitation assays in BSC-40 cells. REBP can modestly
      enhance Rev-dependent RRE-linked reporter gene expression both independently and
      in cooperation with the nucleoporin cofactor Rab/hRIP. Thus, REBP displays the
      characteristics expected of an authentic mediator of Rev NES function and may
      play a role in RRE RNA transport during HIV infection.

PMID- 12805423
TI  - A live attenuated equine infectious anemia virus proviral vaccine with a modified
      S2 gene provides protection from detectable infection by intravenous virulent
      virus challenge of experimentally inoculated horses.
AB  - Previous evaluations of inactivated whole-virus and envelope subunit vaccines to
      equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy
      ranging from highly type-specific protection to severe enhancement of viral
      replication and disease in experimentally immunized equids. Among experimental
      animal lentivirus vaccines, immunizations with live attenuated viral strains have
      proven most effective, but the vaccine efficacy has been shown to be highly
      dependent on the nature and severity of the vaccine virus attenuation. We
      describe here for the first time the characterization of an experimental
      attenuated proviral vaccine, EIAV(UK)deltaS2, based on inactivation of the S2
      accessory gene to down regulate in vivo replication without affecting in vitro
      growth properties. The results of these studies demonstrated that immunization
      with EIAV(UK)deltaS2 elicited mature virus-specific immune responses by 6 months
      and that this vaccine immunity provided protection from disease and detectable
      infection by intravenous challenge with a reference virulent biological clone,
      EIAV(PV). This level of protection was observed in each of the six experimental
      horses challenged with the reference virulent EIAV(PV) by using a low-dose
      multiple-exposure protocol (three administrations of 10 median horse infectious
      doses [HID(50)], intravenous) designed to mimic field exposures and in all three
      experimentally immunized ponies challenged intravenously with a single
      inoculation of 3,000 HID(50). In contrast, naive equids subjected to the low- or
      high-dose challenge develop a detectable infection of challenge virus and acute
      disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene
      provides an optimal site for modification to achieve the necessary balance
      between attenuation to suppress virulence and replication potential to
      sufficiently drive host immune responses to produce vaccine immunity to viral
      exposure.

PMID- 12805424
TI  - Interaction of rotaviruses with Hsc70 during cell entry is mediated by VP5.
AB  - Rotavirus infection seems to be a multistep process in which the viruses are
      required to interact with several cell surface molecules to enter the cell. The
      virus spike protein VP4, which is cleaved by trypsin into two subunits, VP5 and
      VP8, is involved in some of these interactions. We have previously shown that the
      neuraminidase-sensitive rotavirus strain RRV initially attaches to a sialic acid
      containing cell molecule through the VP8 subunit of VP4 and subsequently
      interacts with integrin alpha2beta1 through VP5. After these initial contacts,
      the virus interacts with at least two additional proteins located at the cell
      surface, the integrin alphavbeta3 and the heat shock cognate protein Hsc70. In
      this work, we have shown that rotavirus RRV and its neuraminidase-resistant
      variant nar3 interact with Hsc70 through a VP5 domain located between amino acids
      642 and 658 of the protein. This conclusion is based on the observation that a
      recombinant protein comprising the 300 carboxy-terminal amino acids of VP5 binds
      specifically to Hsc70 and a synthetic peptide containing amino acids 642 to 658
      competes with the binding of the RRV and nar3 viruses to the heat shock protein.
      The VP5 peptide also competed with the binding to Hsc70 of the recombinant VP5
      protein, and an antibody to Hsc70 reduced the binding of the recombinant protein
      to the surface of MA104 cells. The fact that the synthetic peptide blocks the
      infectivity of rotaviruses RRV and nar3 but not their binding to cells indicates
      that the interaction of VP5 with Hsc70 most probably occurs at a postattachment
      step during the virus entry process.

PMID- 12805425
TI  - NF-kappaB is required for apoptosis prevention during herpes simplex virus type 1
      infection.
AB  - Wild-type herpes simplex virus type 1 (HSV-1) infection triggers apoptosis in
      human cells. The subsequent synthesis of infected cell proteins between 3 and 6 h
      postinfection (hpi) acts to block this process from killing the cells. The
      factors produced during this window also prevent cell death induced by
      environmental staurosporine or sorbitol (M. Aubert, J. O'Toole, and J. A. Blaho,
      J. Virol. 73:10359-10370, 1999). We now report that (i) during the prevention
      window, HSV-1(F) also inhibited apoptosis induced by tumor necrosis factor alpha
      (TNF-alpha) plus cycloheximide (CHX) treatment. While deciphering the mechanism
      of this inhibition, we observed that (ii) the transcription factor NF-kappaB
      translocated from the cytoplasm into the nuclei of infected cells, and (iii) this
      migration initiated at 3 hpi. (iv) The complete inhibition of protein synthesis
      at 3 hpi by the addition of CHX precluded NF-kappaB translocation, while CHX
      additions at 6 hpi or later did not elicit this effect. This result confirms that
      infected cell protein synthesis is required for the nuclear import of NF-kappaB.
      (v) The detection of NF-kappaB in nuclei correlated with the ability of HSV-1(F),
      HSV-1(KOS1.1), or HSV-1(R7032), a replication-competent recombinant virus
      containing a deletion in the gene encoding the gE glycoprotein, to prevent
      apoptosis. (vi) NF-kappaB did not bind its kappaB DNA recognition site and
      remained cytoplasmic in cells actively undergoing apoptosis following infection
      with HSV-1(vBSdelta27), a virus with the key regulatory protein ICP27 deleted.
      (vii) Prestimulation of NF-kappaB by the addition of a phorbol ester prevented
      HSV-1(vBSdelta27)-induced apoptosis. (viii) Retention of NF-kappaB in the
      cytoplasm by the addition of a pharmacological antagonist of its release from
      IkappaBalpha led to an increase in death factor processing during HSV-1(F)
      infection. (ix) A novel HEp-2 clonal cell line, termed IkappaBalphaDN, was
      generated which expresses a dominant-negative form of IkappaBalpha. Treatment of
      IkappaBalphaDN cells with TNF-alpha in the absence of CHX resulted in apoptotic
      death due to the inability of NF-kappaB to become activated in these cells.
      Finally, (x) infection of IkappaBalphaDN cells with HSV-1(F) or HSV-1(KOS1.1)
      resulted in apoptosis, demonstrating that (xi) the nuclear translocation of NF
      kappaB between 3 and 6 hpi (the prevention window) is necessary to prevent
      apoptosis in wild-type HSV-1-infected human HEp-2 cells.

PMID- 12805426
TI  - High-frequency genetic recombination and reactivation of orthopoxviruses from DNA
      fragments transfected into leporipoxvirus-infected cells.
AB  - Poxvirus DNA is not infectious because establishing an infection requires the
      activities of enzymes packaged in the virion. This barrier can be overcome by
      transfecting virus DNA into cells previously infected with another poxvirus,
      since the resident virus can provide the trans-acting systems needed to
      reactivate transfected DNA. In this study we show that cells infected with a
      leporipoxvirus, Shope fibroma virus (SFV), can reactivate vaccinia virus DNA.
      Similar heterologous packaging systems which used fowlpox-infected cells to
      reactivate vaccinia virus have been described, but SFV-infected cells promoted a
      far more efficient reaction that can produce virus titers exceeding 10(6) PFU/
      micro g of transfected DNA. SFV-promoted reactions also exploit the
      hyperrecombinogenic systems previously characterized in SFV-infected cells, and
      these coupled recombination and reactivation reactions could be used to delete
      nonessential regions of the vaccinia virus genome and to reconstruct vaccinia
      virus from overlapping DNA fragments. SFV-catalyzed recombination reactions need
      only two 18- to 20-bp homologies to target PCR amplicons to restriction enzyme
      cut vaccinia virus vectors, and this reaction feature was used to rapidly clone
      and express a gene encoding fluorescent green protein without the need for plaque
      purification or selectable markers. The ability of SFV-infected cells to
      reactivate fragments of vaccinia virus was ultimately limited by the number of
      recombinational exchanges required and one cannot reconstruct vaccinia virus from
      multiple PCR fragments spanning essential portions of the genome. These
      observations suggest that recombination is an integral part of poxvirus
      reactivation reactions and provide a useful new technique for altering the
      structure of poxvirus genomes.

PMID- 12805427
TI  - p21(Waf1/Cip1/Sdi1) prevents apoptosis as well as stimulates growth in cells
      transformed or immortalized by human T-cell leukemia virus type 1-encoded tax.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) Tax regulates the expression of
      virally encoded genes, as well as various endogenous host genes in trans. Tax
      mediated regulation of gene expression is important for the immortalization of
      normal human T lymphocytes and the transformation of fibroblast cells, such as
      Rat-1 cells. Tax has the ability to transactivate p21(Waf1/Cip1/Sdi1), resulting
      in high expression levels in HTLV-1-immortalized cells. Since p21 expression is
      suppressed due to methylation of the promoter region in Rat-l cell line, p21 may
      not be critical for the transformation of this cell line by Tax. To further
      understand the role of p21 for the proliferation of Tax-transformed Rat-1 cells,
      we examined the effect of ectopic expression of p21 in these cells. Here, we
      observed that p21 expression enhanced the transformation of this cell line via at
      least two mechanisms: (i) the enhancement of NF-kappaB activation and/or CREB
      signaling and (ii) the excitation of antiapoptotic machinery. To analyze the role
      of p21 that is overexpressed in HTLV-1-immortalized lymphocytes, p21 expression
      was suppressed by using an antisense oligonucleotide specific for p21 mRNA; these
      cells then became sensitive to apoptotic induction. These results suggest that
      p21 plays an important role in the proliferation of Tax-expressing cells through
      the regulation of at least two independent mechanisms.

PMID- 12805428
TI  - Yeast-based genetic system for functional analysis of poxvirus mRNA cap
      methyltransferase.
AB  - Structural differences between poxvirus and human mRNA capping enzymes recommend
      cap formation as a target for antipoxviral drug discovery. Genetic and
      pharmacologic analysis of the poxvirus capping enzymes requires in vivo assays in
      which the readout depends on the capacity of the viral enzyme to catalyze cap
      synthesis. Here we have used the budding yeast Saccharomyces cerevisiae as a
      genetic model for the study of poxvirus cap guanine-N7 methyltransferase. The S.
      cerevisiae capping system consists of separate triphosphatase (Cet1),
      guanylyltransferase (Ceg1), and methyltransferase (Abd1) components. All three
      activities are essential for cell growth. We report that the methyltransferase
      domain of vaccinia virus capping enzyme (composed of catalytic vD1-C and
      stimulatory vD12 subunits) can function in lieu of yeast Abd1. Coexpression of
      both vaccinia virus subunits is required for complementation of the growth of
      abd1Delta cells. Previously described mutations of vD1-C and vD12 that eliminate
      or reduce methyltransferase activity in vitro either abolish abd1Delta
      complementation or elicit conditional growth defects. We have used the yeast
      complementation assay as the primary screen in a new round of alanine scanning of
      the catalytic subunit. We thereby identified several new amino acids that are
      critical for cap methylation activity in vivo. Studies of recombinant proteins
      show that the lethal vD1-C mutations do not preclude heterodimerization with vD12
      but either eliminate or reduce cap methyltransferase activity in vitro.

PMID- 12805429
TI  - Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes.
AB  - Intranasal infection of mice with murine gammaherpesvirus 68 (MHV-68), a virus
      genetically related to the human pathogen Kaposi's sarcoma-associated
      herpesvirus, results in a persistent, latent infection in the spleen and other
      lymphoid organs. Here, we have determined the frequency of virus infection in
      splenic dendritic cells, macrophages, and several B-cell subpopulations, and we
      quantified cell type-dependent virus transcription patterns. The frequencies of
      virus genome positive cells were maximal at 14 days postinfection in all splenic
      cell populations analyzed. Marginal zone and germinal center B cells harbored the
      highest frequency of infection and the former population accounted for
      approximately half the total number of infected B cells. Analysis of virus
      transcription during the establishment of latency revealed that virus gene
      expression in B cells was restricted and dependent on the differentiation stage
      of the B cell. Notably, transcription of ORF73 was detected in germinal center B
      cells, a finding in agreement with the predicted latent genome maintenance
      function of ORF73 in dividing cells. At late times after infection, virus DNA
      could only be detected in newly formed and germinal center B cells, which
      suggests that B cells play a critical role in facilitating life-long latency.

PMID- 12805430
TI  - Respiratory syncytial virus nucleoprotein-specific cytotoxic T-cell epitopes in a
      South African population of diverse HLA types are conserved in circulating field
      strains.
AB  - This study identifies memory cytotoxic T lymphocyte (CTL) epitopes to respiratory
      syncytial virus (RSV) in healthy South African adults and demonstrates the
      conservation of those epitopes in circulating field strains of RSV in South
      Africa. Thirty-seven healthy adults from a population with diverse HLA
      backgrounds were screened by gamma interferon (IFN-gamma) enzyme-linked
      immunospot for memory CTL activity in response to overlapping peptides
      representing the complete nucleoprotein (N) of RSV. Responses of more than 40
      spot-forming cells/million cells were detectable in 21 individuals. The
      significant responses were further characterized, and 14-mer peptides were
      identified that induced cytolytic activity. Fine mapping of peptides with the
      highest cytolytic activity identified an HLA-B(*)08-restricted RSV-specific CTL
      epitope. The extended 14-mer peptide containing this epitope also induced lysis
      in the context of A(*)02-restricted target cells in some individuals. These HLA
      types are common in the target population; thus, the epitope is useful for
      studies of CTL responses to RSV in humans. The epitope was detected in healthy
      adults, reflecting the response generated in the course of previous natural RSV
      infection. We obtained a large panel of naturally occurring isolates of RSV to
      determine whether there was evidence of escape from CTL activity in circulating
      strains. We found that this epitope and a previously identified B(*)07-restricted
      N protein epitope were conserved in RSV field strains representing the diversity
      of circulating genotypes. This work suggests that escape from CTL activity is not
      common for this acute respiratory infection.

PMID- 12805431
TI  - Enhanced detection of human immunodeficiency virus type 1-specific T-cell
      responses to highly variable regions by using peptides based on autologous virus
      sequences.
AB  - The antigenic diversity of human immunodeficiency virus type 1 (HIV-1) represents
      a significant challenge for vaccine design as well as the comprehensive
      assessment of HIV-1-specific immune responses in infected persons. In this study
      we assessed the impact of antigen variability on the characterization of HIV-1
      specific T-cell responses by using an HIV-1 database to determine the sequence
      variability at each position in all expressed HIV-1 proteins and a comprehensive
      data set of CD8 T-cell responses to a reference strain of HIV-1 in infected
      persons. Gamma interferon Elispot analysis of HIV-1 clade B-specific T-cell
      responses to 504 overlapping peptides spanning the entire expressed HIV-1 genome
      derived from 57 infected subjects demonstrated that the average amino acid
      variability within a peptide (entropy) was inversely correlated to the measured
      frequency at which the peptide was recognized (P = 6 x 10(-7)). Subsequent
      studies in six persons to assess T-cell responses against p24 Gag, Tat, and Vpr
      peptides based on autologous virus sequences demonstrated that 29% (12 of 42) of
      targeted peptides were only detected with peptides representing the autologous
      virus strain compared to the HIV-1 clade B consensus sequence. The use of
      autologous peptides also allowed the detection of significantly stronger HIV-1
      specific T-cell responses in the more variable regulatory and accessory HIV-1
      proteins Tat and Vpr (P = 0.007). Taken together, these data indicate that
      accurate assessment of T-cell responses directed against the more variable
      regulatory and accessory HIV-1 proteins requires reagents based on autologous
      virus sequences. They also demonstrate that CD8 T-cell responses to the variable
      HIV-1 proteins are more common than previously reported.

PMID- 12805432
TI  - Lentivirus vectors incorporating the immunoglobulin heavy chain enhancer and
      matrix attachment regions provide position-independent expression in B
      lymphocytes.
AB  - In the present studies we developed lentivirus vectors with regulated, consistent
      transgene expression in B lymphocytes by incorporating the immunoglobulin heavy
      chain enhancer (E micro ) with and without associated matrix attachment regions
      (E micro MAR) into lentivirus vectors. Incorporation of these fragments upstream
      of phosphoglycerate kinase (PGK) or cytomegalovirus promoters resulted in a two-
      to threefold increase in enhanced green fluorescent protein (EGFP) mean
      fluorescence intensity (MFI) in B-lymphoid but not T-lymphoid, myeloid,
      fibroblast, or carcinoma cell lines. A 1-log increase in EGFP expression was
      observed in B-lymphoid cells (but not myeloid cells) differentiated from human
      CD34(+) progenitors in vitro transduced with E micro - and E micro MAR-containing
      lentivectors. Lastly, we evaluated the expression from the E micro MAR element in
      mice 2 to 24 weeks posttransplant with transduced hematopoietic stem cells. In
      mice receiving vectors with the E micro and E micro MAR elements upstream of the
      PGK promoter, there was a 2- to 10-fold increase in EGFP expression in B cells
      (but not other cell types). Evaluation of the coefficient of variation of
      expression among different cell types demonstrated that consistent, position
      independent transgene expression was observed exclusively in B cells transduced
      with the E micro MAR-containing vector and not other cells types or vectors.
      Proviral genomes with the E micro MAR element had increased chromatin
      accessibility, which likely contributed to the position independence of
      expression in B lymphocytes. In summary, incorporation of the E micro MAR element
      in lentivirus vectors resulted in enhanced, position-independent expression in
      primary B lymphocytes. These vectors provide a useful tool for the study of B
      lymphocyte biology and the development of gene therapy for disorders affecting B
      lymphocytes, such as immune deficiencies.

PMID- 12805433
TI  - Identification of a single amino acid change in the human respiratory syncytial
      virus L protein that affects transcriptional termination.
AB  - Infectious Human respiratory syncytial virus (HRSV) with an aberrant RNA
      synthesis pattern was recovered from a cDNA clone. The virus displayed increased
      levels of polycistronic readthrough mRNAs resulting from failure of the
      polymerase to terminate transcription efficiently at the gene ends. An asparagine
      (N) to aspartic acid (D) change at amino acid 1049 in the large (L) polymerase
      protein was found to be responsible for the readthrough phenotype. Virus encoding
      N at position 1049 displayed an RNA synthesis pattern indistinguishable from the
      A2 strain of HRSV. We compared the transcriptional activities of polymerases that
      encoded an N or D at position 1049 (L(1049N) or L(1049D)) by using dicistronic
      subgenomic replicons and found that the alteration of amino acid 1049
      specifically affected transcriptional termination but had no effect on genome
      replication. L(1049N) recognized and terminated transcription at each of the
      naturally occurring gene junctions with differing efficiencies but at
      significantly higher efficiency than L(1049D). The abilities of the polymerases
      to recognize the cis-acting gene end signals required for termination were
      compared by examining the effect of single nucleotide changes at positions 1 to 8
      of the M gene end and were found to be similar. This work identifies a single
      amino acid position in the polymerase that specifically affects the ability of
      the polymerase to terminate transcription, but which does not affect genome
      replication or interaction with the M2-1 protein. This work shows the critical
      importance of the previously defined cis-acting signals for termination, confirms
      differential termination at the varied gene junctions, and shows that the
      polymerase responds to the cis-acting sequences similarly, whether it has N or D
      at position 1049.

PMID- 12805434
TI  - Second-strand genome conversion of adeno-associated virus type 2 (AAV-2) and AAV
      5 is not rate limiting following apical infection of polarized human airway
      epithelia.
AB  - Recombinant adeno-associated virus type 5 (rAAV-5) is known to efficiently
      transduce airway epithelia via apical infection. In contrast, rAAV-2 has been
      shown to be inherently ineffective at transducing airway epithelia from the
      apical surface. However, tripeptide proteasome inhibitors (such as LLnL) can
      dramatically enhance rAAV-2 transduction from the apical surface of human
      polarized airway epithelia by modulating the intracellular trafficking and
      processing of the virus. To further investigate potential differences between
      rAAV-2 and rAAV-5 that might explain their altered ability to transduce airway
      epithelia from the apical membrane, we examined the functional involvement of the
      ubiquitin/proteasome pathway and rate-limiting aspects of second-strand synthesis
      for these two rAAV serotypes. To this end, we conducted studies to compare the
      extent to which LLnL alters transduction efficiencies with both rAAV-2 and rAAV
      2/5 by using luciferase and enhanced green fluorescent protein (EGFP) reporter
      vectors. Our results demonstrate that the coadministration of LLnL at the time of
      viral infection significantly enhanced transduction of both rAAV-2/5 and rAAV-2
      from the apical surface of airway epithelia. Although rAAV-2/5 was slightly more
      effective at transducing epithelia from the apical membrane, rAAV-2 transduction
      was superior to that of rAAV-2/5 in the presence of proteasome inhibitors.
      Interestingly, the basolateral membrane entry pathways for both serotypes were
      not significantly affected by the addition of LLnL, which suggests that apical
      and basolateral infectious pathways possess distinctive intracellular processing
      pathways for both rAAV-2 and rAAV-5. Studies comparing the transduction of short
      self-complementary (scAAV) to full-length conventional AAV EGFP vectors suggested
      that second-strand synthesis of rAAV genomes was not rate limiting for either
      serotype or altered by proteasome inhibitors following apical infection of
      polarized airway epithelia. These findings suggest that both rAAV-2 and rAAV-5
      share similar intracellular viral processing barriers that involve the
      ubiquitin/proteasome system, but do not appear to involve second-strand
      synthesis.

PMID- 12805435
TI  - Viral escape from dominant simian immunodeficiency virus epitope-specific
      cytotoxic T lymphocytes in DNA-vaccinated rhesus monkeys.
AB  - Virus-specific cytotoxic T lymphocytes (CTL) are critical for control of human
      immunodeficiency virus type 1 replication. However, viral escape from CTL
      recognition can undermine this immune control. Here we demonstrate the high
      frequency and pattern of viral escape from dominant epitope-specific CTL in SIV
      gag DNA-vaccinated rhesus monkeys following a heterologous simian
      immunodeficiency virus (SIV) challenge. DNA-vaccinated monkeys exhibited initial
      effective control of the SIV challenge, but this early control was lost by serial
      breakthroughs of viral replication over a 3-year follow-up period. Increases in
      plasma viral RNA correlated temporally with declines of dominant SIV epitope
      specific CD8(+) T-lymphocyte responses and the emergence of viral mutations that
      escaped recognition by dominant epitope-specific CTL. Viral escape from CTL
      occurred in a total of seven of nine vaccinated and control monkeys, including
      three animals that initially controlled viral replication to undetectable levels
      of plasma viral RNA. These data suggest that CTL exert selective pressure on
      viral replication and that viral escape from CTL may be a limitation of CTL-based
      AIDS vaccine strategies.

PMID- 12805436
TI  - Identification of the murine coronavirus MP1 cleavage site recognized by papain
      like proteinase 2.
AB  - The replicase polyprotein of murine coronavirus is extensively processed by three
      proteinases, two papain-like proteinases (PLPs), termed PLP1 and PLP2, and a
      picornavirus 3C-like proteinase (3CLpro). Previously, we established a trans
      cleavage assay and showed that PLP2 cleaves the replicase polyprotein between
      p210 and membrane protein 1 (MP1) (A. Kanjanahaluethai and S. C. Baker, J. Virol.
      74:7911-7921, 2000). Here, we report the results of our studies identifying and
      characterizing this cleavage site. To determine the approximate position of the
      cleavage site, we expressed constructs that extended various distances upstream
      from the previously defined C-terminal end of MP1. We found that the construct
      extending from the putative PLP2 cleavage site at glycine 2840-alanine 2841 was
      most similar in size to the processed MP1 replicase product generated in a trans
      cleavage assay. To determine which amino acids are critical for PLP2 recognition
      and processing, we generated 14 constructs with amino acid substitutions upstream
      and downstream of the putative cleavage site and assessed the effects of the
      mutations in the PLP2 trans-cleavage assay. We found that substitutions at
      phenylalanine 2835, glycine 2839, or glycine 2840 resulted in a reduction in
      cleavage of MP1. Finally, to unequivocally identify this cleavage site, we
      isolated radiolabeled MP1 protein and determined the position of
      [(35)S]methionine residues released by Edman degradation reaction. We found that
      the amino-terminal residue of MP1 corresponds to alanine 2841. Therefore, murine
      coronavirus PLP2 cleaves the replicase polyprotein between glycine 2840 and
      alanine 2841, and the critical determinants for PLP2 recognition and processing
      occupy the P6, P2, and P1 positions of the cleavage site. This study is the first
      report of the identification and characterization of a cleavage site recognized
      by murine coronavirus PLP2 activity.

PMID- 12805437
TI  - Analysis of human immunodeficiency virus type 1 gene expression in latently
      infected resting CD4+ T lymphocytes in vivo.
AB  - In individuals with human immunodeficiency virus type 1 (HIV-1) infection, a
      small reservoir of resting memory CD4(+) T lymphocytes carrying latent,
      integrated provirus persists even in patients treated for prolonged periods with
      highly active antiretroviral therapy (HAART). This reservoir greatly complicates
      the prospects for eradicating HIV-1 infection with antiretroviral drugs.
      Therefore, it is critical to understand how HIV-1 latency is established and
      maintained. In particular, it is important to determine whether transcriptional
      or posttranscriptional mechanisms are involved. Therefore, HIV-1 DNA and mRNAs
      were measured in highly purified populations of resting CD4(+) T lymphocytes from
      the peripheral blood of patients on long-term HAART. In such patients, the
      predominant form of persistent HIV-1 is latent integrated provirus. Typically,
      100 HIV-1 DNA molecules were detected per 10(6) resting CD4(+) T cells. Only very
      low levels of unspliced HIV-1 RNA ( approximately 50 copies/10(6) resting CD4(+)
      T cells) were detected using a reverse transcriptase PCR assay capable of
      detecting a single molecule of RNA standard. Levels of multiply spliced HIV-1 RNA
      were below the limit of detection (<50 copies/10(6) cells). Only 1% of the HIV-1
      DNA-positive lymphocytes in this compartment could be induced to up-regulate HIV
      1 mRNAs after cellular activation, indicating that most of the proviral DNA in
      resting CD4(+) T cells either carries intrinsic defects precluding transcription
      or is subjected to transcriptional control mechanisms that preclude high-level
      production of multiply spliced mRNAs. Nevertheless, by inducing T-cell
      activation, it is possible to isolate replication-competent virus from resting
      CD4(+) T lymphocytes of all infected individuals, including those on prolonged
      HAART. Thus, a subset of integrated proviruses (1%) remains competent for high
      level mRNA production after cellular activation, and a subset of these can
      produce infectious virus. Measurements of steady-state levels of multiply spliced
      and unspliced HIV-1 RNA prior to cellular activation suggest that infected
      resting CD4(+) T lymphocytes in blood synthesize very little viral RNA and are
      unlikely to be capable of producing virus. In these cells, latency appears to
      reflect regulation at the level of mRNA production rather than at the level of
      splicing or nuclear export of viral mRNAs.

PMID- 12805438
TI  - The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven
      inflammation.
AB  - The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist
      of many chemokine receptors believed to be associated with attraction of T cells
      with a type 1 cytokine profile. For the present report we have studied the in
      vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell
      mediated inflammation. This was done by use of the well-established model system
      murine lymphocytic choriomeningitis virus infection. Mice were infected in the
      footpad, and the induced CD8(+) T-cell-dependent inflammation was evaluated in
      mice subjected to treatment with vMIP-II. We found that inflammation was markedly
      inhibited in mice treated during the efferent phase of the antiviral immune
      response. In vitro studies revealed that vMIP-II inhibited chemokine-induced
      migration of activated CD8(+) T cells, but not T-cell-target cell contact,
      granule exocytosis, or cytokine release. Consistent with these in vitro findings
      treatment with vMIP-II inhibited the adoptive transfer of a virus-specific
      delayed-type hypersensitivity response in vivo, but only when antigen-primed
      donor cells were transferred via the intravenous route and required to migrate
      actively, not when the cells were injected directly into the test site. In
      contrast to the marked inhibition of the effector phase, the presence of vMIP-II
      during the afferent phase of the immune response did not result in significant
      suppression of virus-induced inflammation. Taken together, these results indicate
      that chemokine-induced signals are pivotal in directing antiviral effector cells
      toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type
      1 T-cell-mediated inflammation.

PMID- 12805439
TI  - Ex vivo analysis of T-cell responses to Epstein-Barr virus-encoded oncogene
      latent membrane protein 1 reveals highly conserved epitope sequences in virus
      isolates from diverse geographic regions.
AB  - Epstein-Barr virus (EBV)-encoded oncogene latent membrane protein (LMP) 1, which
      is consistently expressed in multiple EBV-associated malignancies, has been
      proposed as a potential target antigen for any future vaccine designed to control
      these malignancies. However, the high degree of genetic variation in the LMP1
      sequence has been considered a major impediment for its use as a potential
      immunotherapeutic target for the treatment of EBV-associated malignancies. In the
      present study, we have employed a highly efficient strategy, based on ex vivo
      functional assays, to conduct an extensive sequence-wide analysis of LMP1
      specific T-cell responses in a large panel of healthy virus carriers of diverse
      ethnic origin and nasopharyngeal carcinoma patients. By comparing the frequencies
      of T cells specific for overlapping peptides spanning LMP1, we mapped a number of
      novel HLA class I- and class II-restricted LMP1 T-cell epitopes, including an
      epitope with dual HLA class I restriction. More importantly, extensive sequence
      analysis of LMP1 revealed that the majority of the T-cell epitopes were highly
      conserved in EBV isolates from Caucasian, Papua New Guinean, African, and
      Southeast Asian populations, while unique geographically constrained genetic
      variation was observed within one HLA A2 supertype-restricted epitope. These
      findings indicate that conserved LMP1 epitopes should be considered in designing
      epitope-based immunotherapeutic strategies against EBV-associated malignancies in
      different ethnic populations.

PMID- 12805441
TI  - The herpes simplex virus type 1 alkaline nuclease and single-stranded DNA binding
      protein mediate strand exchange in vitro.
AB  - The replication of herpes simplex virus type 1 (HSV-1) DNA is associated with a
      high degree of homologous recombination. While cellular enzymes may take part in
      mediating this recombination, we present evidence for an HSV-1-encoded
      recombinase activity. HSV-1 alkaline nuclease, encoded by the UL12 gene, is a 5'-
      >3' exonuclease that shares homology with Redalpha, commonly known as lambda
      exonuclease, an exonuclease required for homologous recombination by
      bacteriophage lambda. The HSV-1 single-stranded DNA binding protein ICP8 is an
      essential protein for HSV DNA replication and possesses single-stranded DNA
      annealing activities like the Redbeta synaptase component of the phage lambda
      recombinase. Here we show that UL12 and ICP8 work together to effect strand
      exchange much like the Red system of lambda. Purified UL12 protein and ICP8
      mediated the complete exchange between a 7.25-kb M13mp18 linear double-stranded
      DNA molecule and circular single-stranded M13 DNA, forming a gapped circle and a
      displaced strand as final products. The optimal conditions for strand exchange
      were 1 mM MgCl(2), 40 mM NaCl, and pH 7.5. Stoichiometric amounts of ICP8 were
      required, and strand exchange did not depend on the nature of the double-stranded
      end. Nuclease-defective UL12 could not support this reaction. These data suggest
      that diverse DNA viruses appear to utilize an evolutionarily conserved
      recombination mechanism.

PMID- 12805440
TI  - Activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs) by human
      dendritic cells infected with an attenuated influenza A virus expressing a CTL
      epitope derived from the HER-2/neu proto-oncogene.
AB  - The development of cancer vaccines requires approaches to induce expansion and
      functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL)
      effectors which posses cytolytic capability and produce cytokines. Efficient
      induction of such cells is hindered by the poor immunogenicity of tumor antigens
      and by the poor transduction efficiency of dendritic cells (DCs) with current
      nonreplicating vectors. We have investigated the use of influenza A virus, a
      potent viral inducer of CTLs, as a vector expressing the immunodominant HER-2 CTL
      epitope KIF (E75). For this purpose, an attenuated influenza A/PR8/34 virus with
      a truncated nonstructural (NS1) gene was generated containing the E75 epitope in
      its neuraminidase protein (KIF-NS virus). Stimulation of peripheral blood
      mononuclear cells from healthy donors and of tumor-associated lymphocytes from
      ovarian and breast cancer patients with DCs infected with KIF-NS virus (KIF-NS
      DC) induced CTLs that specifically recognized the peptide KIF and HER-2
      expressing tumors in cytotoxicity assays and secreted gamma interferon (IFN
      gamma) and interleukin-2 at recall with peptide. Priming with KIF-NS DCs
      increased the number of E75(+) CD45RO(+) cells by more than 10-fold compared to
      nonstimulated cells. In addition, KIF-NS virus induced high levels of IFN-alpha
      in DCs. This is the first report demonstrating induction of human epitope
      specific CTLs against a tumor-associated antigen with a live attenuated
      recombinant influenza virus vector. Such vectors may provide a novel approach for
      tumor antigen delivery, lymphocyte activation, and differentiation in human
      cancer vaccine development.

PMID- 12805442
TI  - Viability of poliovirus/rhinovirus VPg chimeric viruses and identification of an
      amino acid residue in the VPg gene critical for viral RNA replication.
AB  - Picornaviral RNA replication utilizes a small virus-encoded protein, termed 3B or
      VPg, as a primer to initiate RNA synthesis. This priming step requires
      uridylylation of the VPg peptide by the viral polymerase protein 3D(pol), in
      conjunction with other viral or host cofactors. In this study, we compared the
      viral specificity in 3D(pol)-catalyzed uridylylation reactions between poliovirus
      (PV) and human rhinovirus 16 (HRV16). It was found that HRV16 3D(pol) was able to
      uridylylate PV VPg as efficiently as its own VPg, but PV 3D(pol) could not
      uridylylate HRV16 VPg. Two chimeric viruses, PV containing HRV16 VPg (PV/R16-VPg)
      and HRV16 containing PV VPg (R16/PV-VPg), were constructed and tested for
      replication capability in H1-HeLa cells. Interestingly, only PV/R16-VPg chimeric
      RNA produced infectious virus particles upon transfection. No viral RNA
      replication or cytopathic effect was observed in cells transfected with R16/PV
      VPg chimeric RNA, despite the ability of HRV16 3D(pol) to uridylylate PV VPg in
      vitro. Sequencing analysis of virion RNA isolated from the virus particles
      generated by PV/R16-VPg chimeric RNA identified a single residue mutation in the
      VPg peptide (Glu(6) to Val). Reverse genetics confirmed that this mutation was
      highly compensatory in enhancing replication of the chimeric viral RNA. PV/R16
      VPg RNA carrying this mutation replicated with similar kinetics and magnitude to
      wild-type PV RNA. This cell culture-induced mutation in HRV16 VPg moderately
      increased its uridylylation by PV 3D(pol) in vitro, suggesting that it might be
      involved in other function(s) in addition to the direct uridylylation reaction.
      This study demonstrated the use of chimeric viruses to characterize viral
      specificity and compatibility in vivo between PV and HRV16 and to identify
      critical amino acid residue(s) for viral RNA replication.

PMID- 12805443
TI  - Cytokine profiles in adult mink infected with Aleutian mink disease parvovirus.
AB  - The aim of this study was to examine the levels of gamma interferon (IFN-gamma)-,
      interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear
      cells from mink infected with the Aleutian mink disease parvovirus (ADV). As
      expected, ADV-infected mink developed high plasma gamma globulin values
      (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8(+)) cells
      in the blood during the infection. We quantified the percentages of IFN-gamma-
      and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after
      virus challenge. The results clearly indicated marked increases in the
      percentages of IFN-gamma- and IL-4-producing lymphocytes during ADV infection.
      The total number of IL-8-producing monocytes in the blood of ADV-infected mink
      stayed fairly constant during the infection. In order to characterize the
      phenotype of the cytokine-producing cells, we performed double-labeling
      fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling
      in one channel and cytokine intracellular staining in the other. We found that
      most IFN-gamma and IL-4 in ADV-infected mink was produced by CD8(+) cells, while
      in the uninfected mink, these cytokines were primarily produced by a cell type
      that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was
      almost exclusively produced by monocytes. All of the above findings led us to
      conclude that both Th1- and Th2-driven immune functions are found in mink
      plasmacytosis.

PMID- 12805444
TI  - The 5'-proximal hairpin of turnip yellow mosaic virus RNA: its role in
      translation and encapsidation.
AB  - The RNA genome of turnip yellow mosaic virus (TYMV) consists of more than 6,000
      nucleotides. During a study of the roles of the two hairpins located in its 90
      nucleotide 5' untranslated region, it was observed that stabilization of the 5'
      proximal hairpin leads to a delay in the development of symptoms on plants. This
      delay in symptom development for both locally and systemically infected leaves
      was found to be dependent on a change in the free energy of the hairpin caused by
      introduced mutations. A protoplast transfection assay revealed that the
      accumulation of plus-strand full-length RNA and subgenomic RNA, as well as
      protein expression levels, was affected by hairpin stability. Stabilization of
      this hairpin inhibited translation. A model is proposed in which a destabilized
      5'-proximal hairpin allows maximal translation of the viral proteins. It is
      suggested that this hairpin may exist in close proximity to the 5' cap as long as
      its stability is low enough to enable translation. However, at an acidic pH, the
      hairpin structure becomes more stable and is functionally transformed into the
      initiation signal for viral packaging. Slightly acidic conditions can be found in
      chloroplasts, where TYMV assembly is driven by a low pH generated by active
      photosynthesis.

PMID- 12805445
TI  - Functional analysis of the endogenous retroviral promoter of the human endothelin
      B receptor gene.
AB  - We previously reported that the long terminal repeats (LTRs) of retroviral
      elements belonging to the HERV-E family contribute to the expression of the human
      apolipoprotein C1 (APOC1) and endothelin B receptor (EDNRB) genes by providing
      alternative promoters. While both LTRs were shown to promote transcription in
      vivo and in vitro, their respective activity and tissue specificity appeared to
      differ even though they shared a high degree of sequence identity. In the present
      study, we further characterized the promoter of the EDNRB LTR and delineated the
      regions and motifs required for strong activity. We confirmed the placenta
      restricted expression of the LTR by transient transfections and quantitative real
      time PCR and determined that the retroviral promoter contributes significantly to
      the level of EDNRB transcripts in placenta, where chimeric mRNAs were found to
      represent 15% of overall EDNRB mRNAs. Transient transfection of 5' deletion
      constructs in cells of placental origin identified a motif, named LPE1, between
      positions 111 and 122 of the EDNRB LTR necessary for transcriptional activity.
      Removal of this region, which contains a putative SP1 binding site, abolished
      promoter activity. A second enhancing region resides between positions 175 and
      215 of the LTR and was termed LPE2. Interestingly, this section contained three
      binding sites that were not present in the APOC1 LTR due to minor nucleotide
      differences. The predicted motifs in the EDNRB LTR were found to likely act in
      symbiosis as modifications to any of the three sites reduced transcription by one
      third while alterations to all three eliminated promoter activity. The results
      from this study illustrate how slight variations in transcriptional regulatory
      sequences can have a profound effect on promoter activity and demonstrate the
      complex regulatory effects of human endogenous retrovirus elements on human gene
      expression.

PMID- 12805446
TI  - Conformational changes in the herpes simplex virus ICP8 DNA-binding protein
      coincident with assembly in viral replication structures.
AB  - The herpes simplex virus (HSV) single-stranded DNA-binding protein, ICP8, is
      required for viral DNA synthesis. Before viral DNA replication, ICP8 colocalizes
      with other replication proteins at small punctate foci called prereplicative
      sites. With the onset of viral genome amplification, these proteins become
      redistributed into large globular replication compartments. Here we present the
      results of immunocytochemical and biochemical analysis of ICP8 showing that
      various antibodies recognize distinct forms of ICP8. Using these ICP8-specific
      antibodies as probes for ICP8 structure, we detected a time-dependent appearance
      and disappearance of ICP8 epitopes in immunoprecipitation assays.
      Immunofluorescence staining of ICP8 in cells infected with different HSV mutant
      viruses as well as cells transfected with a limited number of viral genes
      demonstrated that these and other antigenic changes occur coincident with ICP8
      assembly at intranuclear replication structures. Genetic analysis has revealed a
      correlation between the ability of various ICP8 mutant proteins to form the 39S
      epitope and their ability to bind to DNA. These results support the hypothesis
      that ICP8 undergoes a conformational change upon binding to other HSV proteins
      and/or to DNA coincident with assembly into viral DNA replication structures.

PMID- 12805447
TI  - Dynamics of viral and proviral loads of feline immunodeficiency virus within the
      feline central nervous system during the acute phase following intravenous
      infection.
AB  - Animal models of human immunodeficiency virus 1, such as feline immunodeficiency
      virus (FIV), provide the opportunities to dissect the mechanisms of early
      interactions of the virus with the central nervous system (CNS). The aims of the
      present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF),
      ocular fluid, and the plasma of cats in the first 23 weeks after intravenous
      inoculation with FIV(GL8). Proviral loads were also determined within peripheral
      blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of
      infection, virus entered the brain in the majority of animals. Virus distribution
      was initially in a random fashion, with more diffuse brain involvement as
      infection progressed. Virus in the CSF was predictive of brain parenchymal
      infection. While the peak of virus production in blood coincided with
      proliferation within brain, more sustained production appeared to continue in
      brain tissue. In contrast, proviral loads in the brain decreased to undetectable
      levels in the presence of a strengthening PBMC load. A final observation in this
      study was that there was no direct correlation between viral loads in regions of
      brain or ocular tissue and the presence of histopathology.

PMID- 12805448
TI  - Intranasal immunization of guinea pigs with an immunodominant foot-and-mouth
      disease virus peptide conjugate induces mucosal and humoral antibodies and
      protection against challenge.
AB  - Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked
      peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and
      mouth disease virus, raised substantial levels of antipeptide and virus
      neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin
      A in nasal secretions. In groups of animals immunized intranasally without
      adjuvant, 86 percent were fully protected upon challenge with homotypic virus.
      Surprisingly, animals given the peptide conjugates plus the mucosal adjuvant
      cholera toxin were afforded only partial protection in that primary lesions were
      observed in most animals, although spread to other feet was prevented. These
      results indicate that intranasal inoculation with the peptide offers a potential
      route of vaccination against foot-and-mouth disease and may be useful for
      eliciting protection in the upper respiratory tracts of susceptible animals.

PMID- 12805449
TI  - Comprehensive screening reveals strong and broadly directed human
      immunodeficiency virus type 1-specific CD8 responses in perinatally infected
      children.
AB  - Advances in antiviral therapy have dramatically shifted the demographics of
      pediatric human immunodeficiency virus type 1 (HIV-1) infection in the developed
      world, and a growing proportion of perinatally HIV-1-infected children are now
      entering their second or even third decade of life. Although cellular immune
      responses to HIV are known to be weak in early infancy, the magnitude, breadth,
      and specificity of responses later in childhood have not been characterized in
      detail. We performed a comprehensive characterization of HIV-1-specific CD8
      responses in 18 perinatally infected children (age range, 6 to 17 years), most of
      whom were on antiviral therapy, using both previously defined HIV-1 epitopes and
      overlapping peptides spanning all HIV-1 proteins. Multispecific responses were
      detected in all subjects and accounted for a median of 0.25 to 0.3% of all
      peripheral blood mononuclear cells that was similar to the magnitude seen in HIV
      infected adults. CD8 responses were broadly directed at an average of 11 epitopes
      (range, 2 to 27 epitopes) and targeted nearly all HIV-1 proteins, with the
      highest proportion in Gag. Responses were readily detected even in those children
      with suppressed viremia on highly active antiretroviral therapy, although the
      breadth (P = 0.037) and the magnitude (P = 0.021) were significantly lower in
      these subjects. Each child recognized only a small minority of the HIV-1 optimal
      epitopes defined for his or her class I HLA alleles. Together, these data
      indicate that perinatally infected children who survive infancy mount a robust
      HIV-1-specific CD8 response that is much stronger than previously thought and is
      comparable in magnitude and breadth to that of adults. Moreover, this response
      has the potential to be broadened to target more epitopes, making these children
      attractive candidates for immunotherapeutic interventions.

PMID- 12805450
TI  - Replication and IRES-dependent translation are both affected by core coding
      sequences in subgenomic GB virus B replicons.
AB  - The yield of G418-resistant Huh7 cell clones bearing subgenomic dicistronic GB
      virus B (GBV-B) is significantly affected by the insertion of a portion of the
      viral core gene between the GBV-B 5' untranslated region and the exogenous
      neomycin phosphotransferase selector gene (A. De Tomassi, M. Pizzuti, R.
      Graziani, A. Sbardellati, S. Altamura, G. Paonessa, and C. Traboni, J. Virol.
      76:7736-7746, 2002). In this report, we have dissected this phenomenon, examining
      the effects of the insertion of core sequences of different lengths on GBV-B IRES
      dependent translation and RNA replication by using experimental approaches aimed
      at analyzing these two aspects independently. The results achieved indicate that
      an enhancement of translation efficiency does occur and that it correlates with
      the length of the inserted core sequences. Interestingly, the insertion of these
      sequences also has a direct similar effect on the efficiency of replication of
      the GBV-B replicon. These results suggest that in GBV-B replicon RNA and
      potentially in the complete viral genome, the core coding sequences not only are
      part of the IRES but also take part in the replication process, independently of
      the presence of the corresponding whole protein.

PMID- 12805451
TI  - N-Linked glycosylation is required for XC cell-specific syncytium formation by
      the R peptide-containing envelope protein of ecotropic murine leukemia viruses.
AB  - The XC cell line undergoes extensive syncytium formation after infection with
      ecotropic murine leukemia viruses (MLVs) and is frequently used to titrate these
      viruses. This cell line is unique in its response to the ecotropic MLV envelope
      protein (Env) in that it undergoes syncytium formation with cells expressing Env
      protein containing R peptide (R(+) Env), which is known to suppress the fusogenic
      potential of the Env protein in other susceptible cells. To analyze the ecotropic
      receptor, CAT1, in XC cells, a mouse CAT1 tagged with the influenza virus
      hemagglutinin epitope (mCAT1-HA)-expressing retroviral vector was inoculated into
      XC and NIH 3T3 cells. The molecular size of the mCAT1-HA protein expressed in XC
      cells was smaller than that in NIH 3T3 cells due to altered N glycosylation in XC
      cells. Treatment of XC cells with tunicamycin significantly suppressed the
      formation of XC cell syncytia induced by the R(+) Env protein but not that
      induced by the R(-) Env protein. This result indicates that N glycosylation is
      required for XC cell-specific syncytium formation by the R(+) Env protein. The
      R(+) Env protein induced syncytia in XC cells expressing a mutant mCAT1 lacking
      both of two N glycosylation sites, and tunicamycin treatment suppressed syncytium
      formation by R(+) Env in those cells. This suggests that N glycosylation of a
      molecule(s) other than the receptor is required for the induction of XC cell
      syncytia by the R(+) Env protein.

PMID- 12805452
TI  - Kinetic analysis of binding interaction between the subgroup A Rous sarcoma virus
      glycoprotein SU and its cognate receptor Tva: calcium is not required for ligand
      binding.
AB  - Tva is the receptor for subgroup A Rous sarcoma virus, and it contains a single
      LDL-A module which is the site of virus interaction. In this study, we expressed
      the entire extracellular region of Tva (referred to as Ecto-Tva) as a GST fusion
      protein and characterized its refolding properties. We demonstrated that the
      correct folding of the Ecto-Tva protein, like that of the Tva LDL-A module, is
      calcium dependent. We used the IAsys system to measure the kinetics of binding
      between the surface (SU) subunit of the viral glycoprotein and Tva in real time.
      We found that the Ecto-Tva protein and the Tva LDL-A module displayed similar
      affinities for SU, providing direct evidence that the LDL-A module of Tva is the
      only viral interaction domain of the receptor. Furthermore, misfolded Tva
      proteins displayed lower binding affinities to SU, largely due to a decrease in
      their association rates, suggesting that a high association rate between SU and
      Tva is crucial for efficient virus-host interaction. Furthermore, we found that
      calcium did not influence the overall binding affinity between Tva and SU. These
      results indicate that, although calcium is important in facilitating correct
      folding of the LDL-A module of Tva, it is not essential for ligand binding. Thus,
      these results may have broad implications for the mechanism of protein folding
      and ligand recognition of the LDL receptor and other members of the LDL receptor
      superfamily.

PMID- 12805453
TI  - Importance of Vp1 calcium-binding residues in assembly, cell entry, and nuclear
      entry of simian virus 40.
AB  - For polyomaviruses, calcium ions are known to be essential for virion integrity
      and for the assembly of capsid structures. To define the role of calcium ions in
      the life cycle of the virus, we analyzed simian virus 40 (SV40) mutants in which
      structurally deduced calcium-binding amino acids of Vp1 were mutated singly and
      in combination. Our study provides evidence that calcium ions mediate not only
      virion assembly but also the initial infection processes of cell entry and
      nuclear entry. Mutations at Glu48, Glu157, Glu160, Glu216, and/or Glu330 are
      correlated with different extents of packaging defects. The low packaging ability
      of mutant E216R suggests the need to position the Glu216 side chain for proper
      virion formation. All other mutants selected for further analysis produced virus
      like particles (VLPs) but were poorly infectious. The VLPs of mutant E330K could
      not attach to or enter the cell, and mutant E157A-E160A and E216K VLPs entered
      the cell but failed to enter the nucleus, apparently as a result of premature VLP
      dissociation. Our results show that five of the seven acidic side chains at the
      two calcium-binding sites-Glu48 and Glu330 (site 1), Glu157 and Glu160 (site 2),
      and Glu216 (both sites)-are important for SV40 infection. We propose that calcium
      coordination imparts not only stability but also structural flexibility to the
      virion, allowing the acquisition or loss of the ion at the two sites to control
      virion formation in the nucleus, as well as virion structural alterations at the
      cell surface and in the cytoplasm early during infection.

PMID- 12805454
TI  - Antibody-dependent enhancement of Ebola virus infection.
AB  - Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans,
      yet there are still no biologic explanations that adequately account for the
      extreme virulence of these emerging pathogens. Here we show that Ebola Zaire
      virus infection in humans induces antibodies that enhance viral infectivity.
      Plasma or serum from convalescing patients enhanced the infection of primate
      kidney cells by the Zaire virus, and this enhancement was mediated by antibodies
      to the viral glycoprotein and by complement component C1q. Our results suggest a
      novel mechanism of antibody-dependent enhancement of Ebola virus infection, one
      that would account for the dire outcome of Ebola outbreaks in human populations.

PMID- 12805455
TI  - Foci of endemic simian immunodeficiency virus infection in wild-living eastern
      chimpanzees (Pan troglodytes schweinfurthii).
AB  - Simian immunodeficiency virus of chimpanzees (SIVcpz) is the immediate precursor
      to human immunodeficiency virus type 1 (HIV-1), yet remarkably, the distribution
      and prevalence of SIVcpz in wild ape populations are unknown. Studies of SIVcpz
      infection rates in wild chimpanzees are complicated by the species' endangered
      status and by its geographic location in remote areas of sub-Saharan Africa. We
      have developed sensitive and specific urine and fecal tests for SIVcpz antibody
      and virion RNA (vRNA) detection and describe herein the first comprehensive
      prevalence study of SIVcpz infection in five wild Pan troglodytes schweinfurthii
      communities in east Africa. In Kibale National Park in Uganda, 31 (of 52) members
      of the Kanyawara community and 39 (of approximately 145) members of the Ngogo
      community were studied; none were found to be positive for SIVcpz infection. In
      Gombe National Park in Tanzania, 15 (of 20) members of the Mitumba community, 51
      (of 55) members of the Kasekela community, and at least 10 (of approximately 20)
      members of the Kalande community were studied. Seven individuals were SIVcpz
      antibody and/or vRNA positive, and two others had indeterminate antibody results.
      Based on assay sensitivities and the numbers and types of specimens analyzed, we
      estimated the prevalence of SIVcpz infection to be 17% in Mitumba (95% confidence
      interval, 10 to 40%), 5% in Kasekela (95% confidence interval, 4 to 7%), and 30%
      in Kalande (95% confidence interval, 15 to 60%). For Gombe as a whole, the SIVcpz
      prevalence was estimated to be 13% (95% confidence interval, 7 to 25%). SIVcpz
      infection was confirmed in five chimpanzees by PCR amplification of partial pol
      and gp41/nef sequences which revealed a diverse group of viruses that formed a
      monophyletic lineage within the SIVcpzPts radiation. Although none of the 70
      Kibale chimpanzees tested SIVcpz positive, we estimated the likelihood that a 10%
      or higher prevalence existed but went undetected because of sampling and assay
      limitations; this possibility was ruled out with 95% certainty. These results
      indicate that SIVcpz is unevenly distributed among P. t. schweinfurthii in east
      Africa, with foci or "hot spots" of SIVcpz endemicity in some communities and
      rare or absent infection in others. This situation contrasts with that for
      smaller monkey species, in which infection rates by related SIVs are generally
      much higher and more uniform among different groups and populations. The basis
      for the wide variability in SIVcpz infection rates in east African apes and the
      important question of SIVcpz prevalence in west central African chimpanzees (Pan
      troglodytes troglodytes) remain to be elucidated.

PMID- 12805457
TI  - Crystallographic identification of a noncompetitive inhibitor binding site on the
      hepatitis C virus NS5B RNA polymerase enzyme.
AB  - The virus-encoded nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is
      an RNA-dependent RNA polymerase and is absolutely required for replication of the
      virus. NS5B exhibits significant differences from cellular polymerases and
      therefore has become an attractive target for anti-HCV therapy. Using a high
      throughput screen, we discovered a novel NS5B inhibitor that binds to the enzyme
      noncompetitively with respect to nucleotide substrates. Here we report the
      crystal structure of NS5B complexed with this small molecule inhibitor.
      Unexpectedly, the inhibitor is bound within a narrow cleft on the protein's
      surface in the "thumb" domain, about 30 A from the enzyme's catalytic center. The
      interaction between this inhibitor and NS5B occurs without dramatic changes to
      the structure of the protein, and sequence analysis suggests that the binding
      site is conserved across known HCV genotypes. Possible mechanisms of inhibition
      include perturbation of protein dynamics, interference with RNA binding, and
      disruption of enzyme oligomerization.

PMID- 12805456
TI  - Susceptibility of immature and mature Langerhans cell-type dendritic cells to
      infection and immunomodulation by human cytomegalovirus.
AB  - Human cytomegalovirus (CMV) infection initiates in mucosal epithelia and
      disseminates via leukocytes throughout the body. Langerhans cells (LCs), the
      immature dendritic cells (DCs) that reside in epithelial tissues, are among the
      first cells to encounter virus and may play important roles in the immune
      response, as well as in pathogenesis as hosts for viral replication and as
      vehicles for dissemination. Here, we demonstrate that CD34(+) progenitor cell
      derived LC-type DCs exhibit a differentiation state-dependent susceptibility to
      CMV infection. In contrast to the small percentage (3 to 4%) of the immature LCs
      that supported infection, a high percentage (48 to 74%) of mature, LC-derived DCs
      were susceptible to infection with endotheliotropic strains (TB40/E or VHL/E) of
      CMV. These cells were much less susceptible to viral strains AD169varATCC,
      TownevarRIT(3), and Toledo. When exposed to endotheliotropic strains, viral gene
      expression (IE1/IE2 and other viral gene products) and viral replication
      proceeded efficiently in LC-derived mature DCs (mDCs). Productive infection was
      associated with downmodulation of cell surface CD83, CD1a, CD80, CD86, ICAM-1,
      major histocompatibility complex (MHC) class I, and MHC class II on these cells.
      In addition, the T-cell proliferative response to allogeneic LC-derived mDCs was
      attenuated when CMV-infected cultures were used as stimulators. This
      investigation revealed important characteristics of the interaction between CMV
      and the LC lineage of DCs, suggesting that LC-derived mDCs are important to viral
      pathogenesis and immunity through their increased susceptibility to virus
      replication and virus-mediated immune escape.

PMID- 12805458
TI  - Nuclear export of Vpr is required for efficient replication of human
      immunodeficiency virus type 1 in tissue macrophages.
AB  - Retroviruses must gain access to the host cell nucleus for subsequent replication
      and viral propagation. Human immunodeficiency virus type 1 (HIV-1) and other
      primate lentiviruses are distinguished from the gammaretroviruses by their
      ability to infect nondividing cells such as macrophages, an important viral
      reservoir in vivo. Rather than requiring nuclear membrane breakdown during cell
      division, the HIV-1 preintegration complex (PIC) enters the nucleus by traversing
      the central aqueous channel of the limiting nuclear pore complex. The HIV-1 PIC
      contains three nucleophilic proteins, matrix, integrase, and Vpr, all of which
      have been implicated in nuclear targeting. The mechanism by which Vpr can display
      such nucleophilic properties and yet also be available for incorporation into
      virions assembling at the plasma membrane is unresolved. We recently
      characterized Vpr as a nucleocytoplasmic shuttling protein that contains two
      novel nuclear import signals and an exportin-1-dependent nuclear export signal
      (NES). We now demonstrate that mutation of this NES impairs the incorporation of
      Vpr into newly formed virions. Furthermore, we find that the Vpr NES is required
      for efficient HIV replication in tissue macrophages present in human spleens and
      tonsils. These findings underscore how the nucleocytoplasmic shuttling of Vpr not
      only contributes to nuclear import of the HIV-1 PIC but also enables Vpr to be
      present in the cytoplasm for incorporation into virions, leading to enhancement
      of viral spread within nondividing tissue macrophages.

PMID- 12805459
TI  - Poxvirus orthologous clusters: toward defining the minimum essential poxvirus
      genome.
AB  - Increasingly complex bioinformatic analysis is necessitated by the plethora of
      sequence information currently available. A total of 21 poxvirus genomes have now
      been completely sequenced and annotated, and many more genomes will be available
      in the next few years. First, we describe the creation of a database of
      continuously corrected and updated genome sequences and an easy-to-use and
      extremely powerful suite of software tools for the analysis of genomes, genes,
      and proteins. These tools are available free to all researchers and, in most
      cases, alleviate the need for using multiple Internet sites for analysis.
      Further, we describe the use of these programs to identify conserved families of
      genes (poxvirus orthologous clusters) and have named the software suite POCs,
      which is available at www.poxvirus.org. Using POCs, we have identified a set of
      49 absolutely conserved gene families-those which are conserved between the
      highly diverged families of insect-infecting entomopoxviruses and vertebrate
      infecting chordopoxviruses. An additional set of 41 gene families conserved in
      chordopoxviruses was also identified. Thus, 90 genes are completely conserved in
      chordopoxviruses and comprise the minimum essential genome, and these will make
      excellent drug, antibody, vaccine, and detection targets. Finally, we describe
      the use of these tools to identify necessary annotation and sequencing updates in
      poxvirus genomes. For example, using POCs, we identified 19 genes that were
      widely conserved in poxviruses but missing from the vaccinia virus strain Tian
      Tan 1998 GenBank file. We have reannotated and resequenced fragments of this
      genome and verified that these genes are conserved in Tian Tan. The results for
      poxvirus genes and genomes are discussed in light of evolutionary processes.

PMID- 12805460
TI  - Effects of charged cluster mutations on the function of herpes simplex virus type
      1 UL34 protein.
AB  - Herpes simplex virus type 1 (HSV-1) is a DNA virus that acquires an envelope by
      budding into the inner nuclear membrane of an infected cell. Recombinant HSV-1
      lacking the U(L)34 gene cannot undergo this event. U(L)34 and U(L)31, another
      viral protein, colocalize in an infected cell and are necessary and sufficient to
      target both proteins to the inner nuclear envelope. In order to define and
      characterize sequences of U(L)34 that are necessary for primary envelopment to
      occur, a library of 19 U(L)34 charged cluster mutants and a truncation mutant
      lacking the putative transmembrane domain (DeltaTM) were generated. Mutants in
      this library were analyzed in a complementation assay for their ability to
      function in the production of infectious virus. Seven of the mutants failed to
      complement a U(L)34-null virus. The remainder of the mutants complemented at or
      near wild-type U(L)34 levels. Failure of a mutant protein to function might be
      the result of incorrect subcellular localization. To address this possibility,
      confocal microscopy was used to determine the localization of the U(L)34 protein
      in charged cluster mutants and DeltaTM. In transfection-infection experiments,
      all of the functional U(L)34 mutants and four of the six noncomplementing mutants
      localized to the inner nuclear envelope in a manner indistinguishable from that
      of wild-type U(L)34. All of the noncomplementing U(L)34 mutants mediated proper
      localization of U(L)31. Charged clusters critical for U(L)34 function are
      dispersed throughout the protein sequence and do not correlate well with highly
      conserved regions of the protein. These data suggest that U(L)34 has at least one
      function in addition to mediating proper localization of U(L)31 in infected cells
      and provide further support for the role of U(L)34 in mediating proper
      localization of U(L)31 in infected cells.

PMID- 12805461
TI  - Molecular distinction between pathogenic and infectious properties of the prion
      protein.
AB  - Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion
      associated with a human familial prion disease. These animals spontaneously
      develop a fatal neurodegenerative disorder characterized by ataxia, neuronal
      apoptosis, and accumulation in the brain of an aggregated and weakly protease
      resistant form of mutant PrP (designated PG14(spon)). Brain homogenates from
      Tg(PG14) mice fail to transmit disease after intracerebral inoculation into
      recipient mice, indicating that PG14(spon), although pathogenic, is distinct from
      PrP(Sc), the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice
      with exogenous prions of the RML strain induces accumulation of PG14(RML), a
      PrP(Sc) form of the mutant protein that is infectious and highly protease
      resistant. Like PrP(Sc), both PG14(spon) and PG14(RML) display conformationally
      masked epitopes in the central and octapeptide repeat regions. However, these two
      forms differ profoundly in their oligomeric states, with PG14(RML) aggregates
      being much larger and more resistant to dissociation. Our analysis provides new
      molecular insight into an emerging puzzle in prion biology, the discrepancy
      between the infectious and neurotoxic properties of PrP.

PMID- 12805462
TI  - Human immunodeficiency virus type 2 reverse transcriptase activity in model
      systems that mimic steps in reverse transcription.
AB  - Human immunodeficiency virus type 2 (HIV-2) infection is a serious problem in
      West Africa and Asia. However, there have been relatively few studies of HIV-2
      reverse transcriptase (RT), a potential target for antiviral therapy. Detailed
      knowledge of HIV-2 RT activities is critical for development of specific high
      throughput screening assays of potential inhibitors. Here, we have conducted a
      systematic evaluation of HIV-2 RT function, using assays that model specific
      steps in reverse transcription. Parallel studies were performed with HIV-1 RT. In
      general, under standard assay conditions, the polymerase and RNase H activities
      of the two enzymes were comparable. However, when the RT concentration was
      significantly reduced, HIV-2 RT was less active than the HIV-1 enzyme. HIV-2 RT
      was also impaired in its ability to catalyze secondary RNase H cleavage in assays
      that mimic tRNA primer removal during plus-strand transfer and degradation of
      genomic RNA fragments during minus-strand DNA synthesis. In addition, initiation
      of plus-strand DNA synthesis was much less efficient with HIV-2 RT than with HIV
      1 RT. This may reflect architectural differences in the primer grip regions in
      the p66 (HIV-1) and p68 (HIV-2) palm subdomains of the two enzymes. The
      implications of our findings for antiviral therapy are discussed.

PMID- 12805463
TI  - STAT protein interference and suppression of cytokine signal transduction by
      measles virus V protein.
AB  - Measles virus, a paramyxovirus of the Morbillivirus genus, is responsible for an
      acute childhood illness that infects over 40 million people and leads to the
      deaths of more than 1 million people annually (C. J. Murray and A. D. Lopez,
      Lancet 349:1269-1276, 1997). Measles virus infection is characterized by virus
      induced immune suppression that creates susceptibility to opportunistic
      infections. Here we demonstrate that measles virus can inhibit cytokine responses
      by direct interference with host STAT protein-dependent signaling systems.
      Expression of the measles V protein prevents alpha, beta, and gamma interferon
      induced transcriptional responses. Furthermore, it can interfere with signaling
      by interleukin-6 and the non-receptor tyrosine kinase, v-Src. Affinity
      purification demonstrates that the measles V protein associates with cellular
      STAT1, STAT2, STAT3, and IRF9, as well as several unidentified partners.
      Mechanistic studies indicate that while the measles V protein does not interfere
      with STAT1 or STAT2 tyrosine phosphorylation, it causes a defect in IFN-induced
      STAT nuclear accumulation. The defective STAT nuclear redistribution is also
      observed in measles virus-infected cells, where some of the STAT protein is
      detected in cytoplasmic bodies that contain viral nucleocapsid protein and
      nucleic acids. Interference with STAT-inducible transcription may provide a novel
      intracellular mechanism for measles virus-induced cytokine inhibition that links
      innate immune evasion to adaptive immune suppression.

PMID- 12805464
TI  - Classical swine fever virus interferes with cellular antiviral defense: evidence
      for a novel function of N(pro).
AB  - Classical swine fever virus (CSFV) replicates efficiently in cell lines and
      monocytic cells, including macrophages (MPhi), without causing a cytopathic
      effect or inducing interferon (IFN) secretion. In the present study, the capacity
      of CSFV to interfere with cellular antiviral activity was investigated. When the
      porcine kidney cell line SK-6 was infected with CSFV, there was a 100-fold
      increased capacity to resist to apoptosis induced by polyinosinic-polycytidylic
      acid [poly(IC)], a synthetic double-stranded RNA. In MPhi, the virus infection
      inhibited poly(IC)-induced alpha/beta IFN (type I IFN) synthesis. This
      interference with cellular antiviral defense correlated with the presence of the
      viral N(pro) gene. Mutants lacking the N(pro) gene (DeltaN(pro) CSFV) did not
      protect SK-6 cells from poly(IC)-induced apoptosis, despite growth properties and
      protein expression levels similar to those of the wild-type virus. Furthermore,
      DeltaN(pro) CSFV did not prevent poly(IC)-induced type I IFN production in MPhi
      but rather induced type I IFN in the absence of poly(IC) in both MPhi and the
      porcine kidney cell line PK-15, but not in SK-6 cells. With MPhi and PK-15, an
      impaired replication of the DeltaN(pro) CSFV compared with wild-type virus was
      noted. In addition, DeltaN(pro) CSFV, but not wild-type CSFV, could interfere
      with vesicular stomatitis virus replication in PK-15 cells. Taken together, these
      results provide evidence for a novel function associated with CSFV N(pro) with
      respect to the inhibition of the cellular innate immune system.

PMID- 12805465
TI  - Mutational analysis of the HLA class II interaction with Epstein-Barr virus
      glycoprotein 42.
AB  - Entry of Epstein-Barr virus (EBV) into B lymphocytes requires the binding of
      viral glycoprotein 42 (gp42), a C-type lectin family member, to HLA class II.
      Recently, the structure of the gp42:HLA-DR1 complex was determined. In order to
      confirm the interaction as determined in the structural study and to identify
      other potential interactive residues, a mutational analysis of HLA class II was
      performed. A secreted form of gp42 (sgp42) reacted with a conformation-specific
      monoclonal antibody and blocked EBV infection. The binding of sgp42 and EBV entry
      to two sets of HLA class II mutants were tested. The first set of mutants were
      based on the known interaction of the C-type lectin Ly49A with HLA class I, and
      the second set of mutants were based on the identified interface in the gp42:HLA
      DR1 complex. As expected, none of the mutants that would be predicted to
      interfere with the interaction of Ly49A with class I affected the interaction of
      gp42 with HLA class II, whereas mutants in amino acids identified in the gp42:HLA
      DR1 structure inhibited sg42 binding to class II. In general, sgp42 binding
      correlated with efficient entry of EBV, as demonstrated by the necessity of
      glutamic acid 46 or arginine 72 in class II molecules. Furthermore, other HLA
      class II residues buried within the interface of gp42 and HLA class II when
      mutated had either no effect or a decrease in both binding and entry and
      implicate a region of class II important in stabilizing the interaction with
      gp42. These studies provide insight into the entry and fusion processes of the
      critical interaction between gp42 and HLA class II.

PMID- 12805466
TI  - Vaccine-induced immunity in baboons by using DNA and replication-incompetent
      adenovirus type 5 vectors expressing a human immunodeficiency virus type 1 gag
      gene.
AB  - The cellular immunogenicity of formulated plasmid DNA and replication-defective
      human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized
      human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5
      vaccine was capable of inducing consistently strong, long-lived CD8(+)-biased T
      cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune
      responses were weaker than those elicited by the Ad5 vaccine and highly variable;
      formulation with chemical adjuvants led to moderate increases in the levels of
      Gag-specific T cells. Increasing the DNA-primed responses with booster doses of
      either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in
      the relative levels of cytotoxic and helper responses. The implications of these
      results are discussed.

PMID- 12805467
TI  - Direct evidence that C-peptide inhibitors of human immunodeficiency virus type 1
      entry bind to the gp41 N-helical domain in receptor-activated viral envelope.
AB  - While it has been established that peptides modeling the C-helical region of
      human immunodeficiency virus type 1 gp41 are potent in vivo inhibitors of virus
      replication, their mechanism of action has yet to be determined. It has been
      proposed, but never directly demonstrated, that these peptides block virus entry
      by interacting with gp41 to disrupt the formation or function of a six-helix
      bundle structure. Using a six-helix bundle-specific monoclonal antibody with
      isolate-restricted Env reactivity, we provide the first direct evidence that, in
      receptor-activated viral Env, C-peptide entry inhibitors bind to the gp41 N
      helical coiled-coil to form a peptide/protein hybrid structure and, in doing so,
      disrupt native six-helix bundle formation.

PMID- 12805468
TI  - Coexistence of two distinct secretion mutations (P5T and I97L) in hepatitis B
      virus core produces a wild-type pattern of secretion.
AB  - Unlike a Tokyo isolate of hepatitis B virus variants, we found a Shanghai isolate
      that secretes few virions with an immature genome despite its core I97L mutation.
      Core mutations P5T and I97L were found to be mutually compensatory in offsetting
      their respective distinct effects on virion secretion.

PMID- 12805469
TI  - Replication-competent hybrids between murine leukemia virus and foamy virus.
AB  - Replication-competent chimeric retroviruses constructed of members of the two
      subfamilies of Retroviridae, orthoretroviruses and spumaretroviruses,
      specifically murine leukemia viruses (MuLV) bearing hybrid MuLV-foamy virus (FV)
      envelope (env) genes, were characterized. All viruses had the cytoplasmic tail of
      the MuLV transmembrane protein. In ESL-1, a truncated MuLV leader peptide (LP)
      was fused to the complete extracellular portion of FV Env, and ESL-2 to -4
      contained the complete MuLV-LP followed by N-terminally truncated FV Env
      decreasing in size. ESL-1 to -4 had an extended host cell range compared to MuLV,
      induced a cytopathology reminiscent of FVs, and exhibited an ultrastructure that
      combined the features of the condensed core of MuLV with the prominent surface
      knobs of FVs. Replication of ESL-2 to -4 resulted in the acquisition of a stop
      codon at the N terminus of the chimeric Env proteins. This mutation rendered the
      MuLV-LP nonfunctional and indicated that the truncated FV-LP was sufficient to
      direct Env synthesis into the secretory pathway. Compared to the parental
      viruses, the chimeras replicated with only moderate cell-free titers.

PMID- 12805470
TI  - High frequency of syncytium-inducing and CXCR4-tropic viruses among human
      immunodeficiency virus type 1 subtype C-infected patients receiving
      antiretroviral treatment.
AB  - Human immunodeficiency virus type 1 (HIV-1) subtype C viruses have been found to
      almost exclusively use the chemokine receptor CCR5 as a coreceptor for entry,
      even in patients with advanced AIDS. We have characterized subtype C virus
      isolates from 28 patients from Harare, Zimbabwe, 20 of whom were receiving
      antiretroviral treatment. Virus from 10 of the treated patients induced syncytium
      formation (SI virus) when cultured with MT2 cells. Only non-syncytium-inducing
      (NSI) virus was cultured from the peripheral blood mononuclear cells of the eight
      patients who had not received treatment. The majority of these subtype C SI
      viruses were capable of using both CCR5 and CXCR4 as coreceptors for viral entry,
      and the consensus V3 loop sequences from the SI viruses displayed a high net
      charge compared to those of NSI viruses. While those on treatment had reverse
      transcriptase (RT) and protease mutations, there was no clear association between
      RT and protease drug resistance mutations and coreceptor tropism. These results
      suggest that CXCR4-tropic viruses are present within the quasispecies of patients
      infected with subtype C virus and that antiretroviral treatment may create an
      environment for the emergence of CXCR4 tropism.

PMID- 12805471
TI  - Episomal persistence of recombinant adenoviral vector genomes during the cell
      cycle in vivo.
AB  - Previously we showed that recombinant adenoviral helper-dependent (HD) vectors
      result in long-term transgene expression levels in vivo which slowly declined by
      95% over a period of 1 year. In this study, we further establish that this was
      not predominantly immune mediated. To determine if cell turnover was responsible
      for the loss of transgene expression, we induced rapid hepatocyte cell cycling in
      mouse liver, by performing a surgical two-thirds partial hepatectomy. We observed
      a 55 and 65% reduction in transgene expression levels and a 50 and 71% loss of
      vector genomes for the HD vector and the first-generation adenoviral vector. In
      sharp contrast, in nonviral, episomal plasmid DNA-injected mice, transgene
      expression levels and DNA copy numbers decreased by 95 and 99%, respectively.
      These findings suggest that cell division alone was not the primary reason for
      the slow decrease in transgene expression levels and that recombinant adenoviral
      vectors have a more robust mechanism for maintaining persistence during cell
      cycling. Several potential mechanisms are proposed.

PMID- 12805472
TI  - Establishment and maintenance of gammaherpesvirus latency are independent of
      infective dose and route of infection.
AB  - Gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated
      herpesvirus are important human pathogens that establish long-term latent
      infections. Understanding of the initiation and maintenance of latent infections
      has important implications for the prevention and treatment of gammaherpesvirus
      related diseases. Although much is known about gammaherpesvirus pathogenesis, it
      is unclear how the infectious dose of a virus influences its ability to establish
      latent infection. To examine the relationship between the infectious dose and
      gammaherpesvirus latency, we inoculated wild-type mice with 0.01 to 10(6) PFU of
      murine gammaherpesvirus 68 (gammaHV68) and quantitatively measured latency and
      acute-phase replication. Surprisingly, during latency, the frequencies of ex vivo
      reactivation were similar over a 10(7)-fold range of doses for i.p. infection and
      over a 10(4)-fold range of doses for intranasal infection. Further, the
      frequencies of cells harboring viral genome during latency did not differ
      substantially over similar dose ranges. Although the kinetics of acute-phase
      replication were delayed at small doses of virus, the peak titer did not differ
      significantly between mice infected with a large dose of virus and those infected
      with a small dose of virus. The results presented here indicate that any
      initiation of infection leads to substantial acute-phase replication and
      subsequent establishment of a maximal level of latency. Thus, infections with
      doses as small as 0.1 PFU of gammaHV68 result in stable levels of acute-phase
      replication and latent infection. These results demonstrate that the equilibrium
      level of establishment of gammaherpesvirus latency is independent of the
      infectious dose and route of infection.

PMID- 12805473
TI  - Short-term effect of zidovudine on plasma and genital human immunodeficiency
      virus type 1 and viral turnover in these compartments.
AB  - The effect of zidovudine on plasma and genital human immunodeficiency virus type
      1 (HIV-1) was determined in 42 antiretroviral-naive HIV-1-seropositive women in
      Nairobi. After 7 days of zidovudine treatment, HIV-1 RNA levels decreased by 0.5
      to 1.1 log(10) in plasma and genital secretions. HIV-1 RNA half-life following
      zidovudine treatment was 4.7, 1.3, and 0.9 days in plasma, cervix, and vagina,
      respectively, and significantly shorter in genital secretions than in plasma (P <
      0.001). Defining the short-term effect of zidovudine on plasma and genital HIV-1
      is important for improving perinatal HIV-1 interventions.

PMID- 12805474
TI  - The cholinergic hypothesis of age and Alzheimer's disease-related cognitive
      deficits: recent challenges and their implications for novel drug development.
AB  - The cholinergic hypothesis was initially presented over 20 years ago and suggests
      that a dysfunction of acetylcholine containing neurons in the brain contributes
      substantially to the cognitive decline observed in those with advanced age and
      Alzheimer's disease (AD). This premise has since served as the basis for the
      majority of treatment strategies and drug development approaches for AD to date.
      Recent studies of the brains of patients who had mild cognitive impairment or
      early stage AD in which choline acetyltransferase and/or acetylcholinesterase
      activity was unaffected (or even up-regulated) have, however, led some to
      challenge the validity of the hypothesis as well as the rationale for using
      cholinomimetics to treat the disorder, particularly in the earlier stages. These
      challenges, primarily based on assays of post mortem enzyme activity, should be
      taken in perspective and evaluated within the wide range of cholinergic
      abnormalities known to exist in both aging and AD. The results of both post
      mortem and antemortem studies in aged humans and AD patients, as well as animal
      experiments suggest that a host of cholinergic abnormalities including
      alterations in choline transport, acetylcholine release, nicotinic and muscarinic
      receptor expression, neurotrophin support, and perhaps axonal transport may all
      contribute to cognitive abnormalities in aging and AD. Cholinergic abnormalities
      may also contribute to noncognitive behavioral abnormalities as well as the
      deposition of toxic neuritic plaques in AD. Therefore, cholinergic-based
      strategies will likely remain valid as one approach to rational drug development
      for the treatment of AD other forms of dementia.

PMID- 12805475
TI  - Prevention of ethanol-induced liver injury in rats by an agonist of peroxisome
      proliferator-activated receptor-gamma, pioglitazone.
AB  - Agonists of peroxisome proliferator-activated receptor (PPAR)-gamma have been
      shown to reduce tumor necrosis factor-alpha (TNF-alpha)-induced insulin
      resistance. On the other hand, sensitization of Kupffer cells to
      lipopolysaccharide (LPS) and their production of TNF-alpha are critical for
      progression of alcoholic liver injury. This study was intended to determine
      whether pioglitazone, a PPAR-gamma agonist, could prevent alcohol-induced liver
      injury. Rats were given ethanol (5 g/kg b.wt.) and pioglitazone (500 microg/kg)
      once every 24 h intragastrically. Ethanol for 8 weeks caused pronounced
      steatosis, necrosis, and inflammation in the liver. These pathological parameters
      were diminished greatly by pioglitazone. Kupffer cells were sensitized to LPS
      after ethanol for 4 weeks as evidenced by aggravation of liver pathology induced
      by LPS (5 mg/kg) and enhancement of LPS (100 ng/ml)-induced intracellular Ca2+
      concentration elevation in Kupffer cells. The parameters were diminished by
      treatment with pioglitazone. LPS-induced TNF-alpha production by Kupffer cells
      from the 4-week ethanol group was 3 to 4 times higher than control. This increase
      was blunted by 70% with pioglitazone. Gut permeability was 10-fold higher in the
      4-week ethanol group, and pioglitazone treatment did not change the value.
      Inclusion of TNF-alpha in culture media of Kupffer cells enhanced CD14
      expression, LPS-induced intracellular Ca2+ concentration response, and production
      of TNF-alpha. These results indicate that pioglitazone prevents alcoholic liver
      injury through abrogation of Kupffer cell sensitization to LPS.

PMID- 12805476
TI  - Comparative effects of methylmercury and Hg(2+) on human neuronal N- and R-type
      high-voltage activated calcium channels transiently expressed in human embryonic
      kidney 293 cells.
AB  - Expression cDNA clones of alpha1B-1 or alpha1E-3 subunits coding for human
      neuronal N-(Cav2.2) or R-subtype (Cav2.3) Ca2+ channels, respectively, was
      combined with alpha2-bdelta and beta3-a Ca2+ channel subunits, and transfected
      into human embryonic kidney cells for transient expression to determine whether
      specific types of neuronal voltage-sensitive Ca2+ channels are affected
      differentially by methylmercury (MeHg) and Hg2+. For both Ca2+ channel subtypes,
      MeHg (0.125-5.0 microM) or Hg2+ (0.1-5 microM) caused a time- and concentration
      dependent reduction of current. MeHg caused an initial, rapid component and a
      subsequent more gradual component of inhibition. The rapid component of block was
      completed between 100 and 150 s after beginning treatment. At 0.125 to 1.25
      microM, MeHg caused a more gradual decline in current. Apparent IC50 values were
      1.3 and 1.1 microM for MeHg, and 2.2 and 0.7 microM for Hg2+ on N- and R-types,
      respectively. For N-type current, effects of Hg2+ were initially greater on the
      peak current than on the sustained current remaining at the end of a test pulse;
      subsequently, Hg2+ blocked both components of current. For R-type current, Hg2+
      affected peak and sustained current approximately equally. Kinetics of
      inactivation also seemed to be affected by Hg2+ in cells expressing N-type but
      not R-type current. Washing with MeHg-free solution could not reverse effects of
      MeHg on either type of current. The effect of Hg2+ on N- but not R-type current
      was partially reversed by Hg2+-free wash solution. Therefore, different types of
      Ca2+ channels have differential susceptibility to neurotoxic mercurials even when
      expressed in the same cell type.

PMID- 12805477
TI  - Dopamine modulation of membrane excitability in striatal spiny neurons is altered
      in DARPP-32 knockout mice.
AB  - The phosphoprotein DARPP-32 (dopamine and cAMP-regulated phosphoprotein 32 kDa)
      plays a central role in mediating the actions of a variety of neurotransmitters
      in medium spiny neurons of the striatum (Greengard, 1990; Fienberg et al., 1998).
      This study examines D1 and D2 dopamine (DA) agonist effects on the membrane
      properties of identified striatal neurons recorded in slices obtained from wild
      type and DARPP-32-knockout mice. In wild-type spiny cells, DA D1 receptor
      activation decreased cell excitability, causing a 58.8 +/- 13.5% increase in
      rheobase current required to evoke spike discharge. In contrast, D1 agonist
      administration did not alter cell excitability when applied to spiny cells in
      slices prepared from the DARPP-32 knockout mice. D2 agonist administration
      decreased cell excitability in both wild-type and knockout mice. The response
      produced by combined D1 and D2 agonist stimulation was dependent on the sequence
      of agonist administration. Thus, the D1 agonist-induced decrease in excitability
      was reversed to a facilitation of spiking upon subsequent D2 agonist
      administration. In contrast, D2 agonist applied simultaneously with the D1
      agonist only produced a reduction in excitability. This type of D1-dependent
      modulation was not present in slices from the DARPP-32 knockout mice.

PMID- 12805478
TI  - Potentiation of N-methyl-D-aspartate-induced currents by the nootropic drug
      nefiracetam in rat cortical neurons.
AB  - Nefiracetam is a new pyrrolidone nootropic drug being developed for the treatment
      of Alzheimer's type and post-stroke vascular-type dementia. In the brain of
      Alzheimer's disease patients, down-regulation of both cholinergic and
      glutamatergic systems has been found and is thought to play an important role in
      impairment of cognition, learning and memory. We have previously shown that the
      activity of neuronal nicotinic acetylcholine receptors is potently augmented by
      nefiracetam. The present study was undertaken to elucidate the mechanism of
      action of nefiracetam on glutamatergic receptors. Currents were recorded from rat
      cortical neurons in long-term primary culture using the whole-cell patch-clamp
      technique at a holding potential of -70 mV in Mg2+-free solutions. N-Methyl-D
      aspartate (NMDA)-evoked currents were greatly and reversibly potentiated by bath
      application of nefiracetam resulting in a bell-shaped dose-response curve. The
      minimum effective nefiracetam concentration was 1 nM, and the maximum
      potentiation to 170% of the control was produced at 10 nM. Nefiracetam
      potentiation occurred at high NMDA concentrations that evoked the saturated
      response, and in a manner independent of NMDA concentrations ranging from 3 to
      1,000 microM. Glycine at 3 microM potentiated NMDA currents but this effect was
      attenuated with an increasing concentration of nefiracetam from 1 to 10,000 nM. 7
      Chlorokynurenic acid at 1 microM prevented nefiracetam from potentiating NMDA
      currents. Nefiracetam at 10 nM shifted the dose-response relationship for the 7
      chlorokynurenic acid inhibition of NMDA currents in the direction of higher
      concentrations. Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid- and
      kainate-induced currents were not significantly affected by application of 10 nM
      nefiracetam. It was concluded that nefiracetam potentiated NMDA currents through
      interactions with the glycine binding site of the NMDA receptor.

PMID- 12805479
TI  - Sympathetic innervation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      primate model of Parkinson's disease.
AB  - Cardiac sympathetic denervation occurs commonly in Parkinson's disease. This
      study explored whether analogous denervation occurs in primates with Parkinsonism
      from systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). 6-[18F]Fluorodopamine positron emission tomographic scanning and plasma
      levels of catecholamines and their deaminated metabolites were used to assess
      sympathetic and adrenomedullary function in rhesus monkeys, in the untreated
      state (n = 3), 2 weeks after a series of four MPTP injections, before
      establishment of Parkinsonism (acute phase, n = 1); a month later, after four
      more MPTP doses, associated with severe Parkinsonism (subacute phase, n = 1); or
      more than 2 years from the last dose (remote phase, n = 3), with persistent
      severe Parkinsonism. A positive control received i.v. 6-hydroxydopamine 1 week
      before 6-[18F]fluorodopamine scanning. Acute MPTP treatment increased cardiac 6
      [18F]fluorodopamine-derived radioactivity, whereas 6-hydroxydopamine markedly
      decreased cardiac radioactivity, despite similarly low plasma levels of
      catecholamines and metabolites after either treatment. Subacutely, plasma
      catecholamines remained decreased, but now with myocardial 6-[18F]fluorodopamine
      derived radioactivity also decreased. Remotely, MPTP-treated monkeys had lower
      plasma catecholamines and higher myocardial 6-[18F]fluorodopamine-derived
      radioactivity than did untreated animals. The results indicate that in nonhuman
      primates, systemic MPTP administration produces multiphasic effects on peripheral
      catecholamine systems, with nearly complete recovery by 2 years. MPTP- and 6
      hydroxydopamine-induced changes differ markedly, probably from ganglionic or
      preganglionic neurotoxicity with the former and more severe cardiac sympathetic
      neurotoxicity with the latter. Because of multiphasic sympathetic and
      adrenomedullary effects, without cardioselective sympathetic denervation at any
      time, the primate MPTP model does not mimic the changes in peripheral
      catecholamine systems that characterize the human disease.

PMID- 12805480
TI  - Evidence for cannabinoid receptor-dependent and -independent mechanisms of action
      in leukocytes.
AB  - Cannabinoids exhibit immunosuppressive actions that include inhibition of
      interleukin-2 production in response to a variety of T cell activation stimuli.
      Traditionally, the effects of these compounds have been attributed to cannabinoid
      receptors CB1 and CB2, both of which are expressed in mouse splenocytes.
      Therefore, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorphenyl)-4-methyl-H
      pyrazole-3 carboxyamidehydrochloride (SR141716A), a CB1 antagonist, and N-[(1S)
      endo-1,3,3,-trimethyl-bicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4
      methylbenzyl)-pyrazole-3-carboxamide (SR144528), a CB2 antagonist, were used to
      investigate the role of cannabinoid receptors in the cannabinoid-induced
      inhibition of phorbol ester plus calcium ionophore (PMA/Io)-stimulated
      interleukin-2 production by mouse splenocytes. PMA/Io-stimulated interleukin-2
      production was inhibited by cannabinol, cannabidiol, and both WIN 55212-2
      stereoisomers with a rank order potency of R-(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl)
      methanone mesylate (WIN 55212-2) approximately cannabidiol > S-(-)-[2,3-dihydro-5
      methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      napthanlenyl) methanone mesylate (WIN 55212-3) approximately cannabinol.
      Cannabinoid-induced inhibition of PMA/Io-stimulated interleukin-2 was not
      attenuated by the presence of both SR144528 and SR141716A. Using pertussis toxin
      to address the role of G protein-coupled receptors in this response, it was
      determined that pertussis toxin treatment did not attenuate cannabinol-induced
      inhibition of PMA/Io-stimulated interleukin-2. With the demonstration that
      cannabinoid-induced inhibition of PMA/Io-stimulated interleukin-2 was not
      mediated via CB1 or CB2, alternative targets of cannabinoids in T cells were
      examined. Specifically, it was demonstrated that cannabinoids elevated
      intracellular calcium concentration in resting splenocytes and that the
      cannabinol-induced elevation in intracellular calcium concentration was
      attenuated by treatment with both SR144528 and SR141716A. Interestingly,
      pretreatment of splenocytes with agents that elevate intracellular calcium
      concentration inhibited PMA/Io-stimulated interleukin-2 production, suggesting
      that an elevation in intracellular calcium concentration might be involved in the
      mechanism of interleukin-2 inhibition. These studies suggest that immune
      modulation produced by cannabinoids involves multiple mechanisms, which might be
      both cannabinoid receptor-dependent and -independent.

PMID- 12805481
TI  - Group II metabotropic and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function
      associated with nicotine withdrawal in rats.
AB  - This study investigated the role of ionotropic and metabotropic glutamate
      receptors in the deficits in brain reward function, as measured by elevations in
      intracranial self-stimulation (ICSS) reward thresholds, associated with nicotine
      withdrawal. The group II metabotropic glutamate (mGluII) receptor agonist
      LY314582 [a racemic mixture of LY354740 ([+]-2-aminobicyclo[3.1.0]hexane-2,6
      dicarboxylic acid])] (2.5-7.5 mg/kg) precipitated withdrawal-like elevations in
      ICSS thresholds, a sensitive measure of reward function, in nicotine-dependent
      but not control rats. LY314582 did not affect response latencies, a measure of
      performance in the ICSS paradigm. Bilateral microinfusion of LY314582 (10-100
      ng/side) into the ventral tegmental area likewise precipitated dose-dependent
      threshold elevations in nicotine-dependent rats. Furthermore, a single injection
      of the mGluII receptor antagonist LY341495 (2S-2-amino-2-[1S,2S-2
      carboxycyclopropan-1-yl]-3-[xanth-9-yl]propionic acid) (1 mg/kg) attenuated the
      threshold elevations observed in rats undergoing spontaneous nicotine withdrawal.
      mGluII receptors are primarily located on glutamatergic terminals throughout the
      mesocorticolimbic system, where they act as inhibitory autoreceptors. To
      investigate whether mGluII receptors contributed to nicotine withdrawal by
      decreasing glutamatergic transmission, we next examined whether direct blockade
      of postsynaptic glutamate receptors precipitated withdrawal-like reward deficits
      in nicotine-dependent rats. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA)/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(f)quinoxaline (NBQX; 0.01-1 mg/kg) precipitated withdrawal-like
      threshold elevations in nicotine-dependent but not control rats, whereas 6-methyl
      2-[phenylethynyl]-pyridine (MPEP; 0.01-3 mg/kg) and dizocilpine (MK-801; 0.01-0.2
      mg/kg), antagonists at metabotropic glutamate 5 and N-methyl-d-aspartate
      receptors, respectively, did not. Overall, these data demonstrate that mGluII
      receptors play an important role in the reward deficits associated with nicotine
      withdrawal. Furthermore, it is likely that mGluII receptors generate this reward
      deficit, at least in part, by decreasing glutamate transmission at AMPA/kainate
      receptors.

PMID- 12805482
TI  - Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione S
      transferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-D
      phenylglycine ethylester.
AB  - Cholangiocarcinoma is markedly resistant to chemotherapy and has a dismal
      prognosis, but its mechanism of drug resistance is unknown. This study examines
      whether glutathione S-transferase-pi (GSTP1-1) is involved in resistance to
      anticancer drugs in cholangiocarcinoma and whether GSTP1-1-specific inhibitors
      can overcome this resistance. First, immunohistochemical examination disclosed
      strong staining of all our 17 cholangiocarcinoma specimens for GSTP1-1,
      irrespective of histological type. Transfection of the GSTP1-1 antisense
      expression vector into a human cholangiocarcinoma cell line (HuCCT1) apparently
      decreased its intracellular GSTP1-1 concentration, and the sensitivity of
      transfectants to adriamycin (ADR), cisplatin, and alkylating agents such as
      melphalan and 4-hydroxyperoxycyclophosphamide (4-HC) was increased significantly,
      compared with that of mock transfectants. We next synthesized GSTP1-1-specific
      inhibitors by elongating the carbon chain of the ethylester at the N-terminal of
      gamma-glutamyl-S-benzylcysteinyl-phenylglycyl diethylester and performed a
      pharmacokinetic study on them. Of six GSTP1-1 inhibitors tested, O1-hexadecyl
      gamma-glutamyl-S-benzylcysteinyl-d-phenylglycine ethylester (C16C2) showed the
      smallest volume of central compartment and smallest volume of distribution at
      steady state and the second smallest clearance, being the most effective
      inhibitor in vivo. The IC50 value of ADR or 4-HC for HuCCT1 cells decreased
      greater by treatment with C16C2 in a dose-dependent manner, paralleling the
      decrease in GSTP1-1 activity, than that of ADR or 4-HC alone. The antitumor
      activity of ADR or cyclophosphamide was clearly enhanced by combination therapy
      with C16C2 in a xenograft model. In conclusion, our results demonstrated that
      GSTP1-1 is a resistance factor for anticancer drugs in cholangiocarcinoma and
      that C16C2, a GSTP1-1-specific inhibitor, is a potent agent against the
      resistance.

PMID- 12805483
TI  - Determination of lipid profile in patients with ischemic stroke or transient
      ischemic attack.

PMID- 12805484
TI  - Editorial comment--Over-the-counter cold remedies and stroke.

PMID- 12805485
TI  - Reliability of assessing percentage of diffusion-perfusion mismatch.
AB  - BACKGROUND AND PURPOSE: Emergent neurovascular imaging holds promise in
      identifying new and optimum target populations for thrombolysis in stroke. Recent
      research has focused on patients with diffusion-weighted MRI (DWI)-perfusion
      weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a
      means to select the most suitable candidates for thrombolysis. The present study
      sought to estimate the reliability of assessing the percentage of DWI-PWI
      mismatch. METHODS: Thirteen patients with acute strokes had DWI and PWI within 7
      hours of symptom onset. Six raters independently created relative mean transit
      time (rMTT) maps and then compared them with DWI images to assess the percentage
      of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4
      raters, tracing around the lesions to calculate the volume percentage of
      mismatch. RESULTS: Visual assessment had an interrater reliability of 0.68 (95%
      CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47
      to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66
      (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI,
      0.81 to 1.0; SEM=10.9%). CONCLUSIONS: Results from the present study suggest that
      quantifying mismatch by the human eye is reproducible but not reliable among
      observers. This raises doubts about using mismatch for clinical decision making
      and clinical trial enrollment.

PMID- 12805486
TI  - Hypothesis of intracerebral hemorrhage growth.

PMID- 12805487
TI  - Racial differences in aortic plaque among ischemic stroke patients.

PMID- 12805488
TI  - Use of the original, modified, or new intracerebral hemorrhage score to predict
      mortality and morbidity after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: A simple clinical scale of intracerebral hemorrhage
      (ICH), comprising the Glasgow Coma Scale score, age, infratentorial origin, ICH
      volume, and intraventricular hemorrhage, was recently shown to predict 30-day
      mortality. We studied how well the original ICH Score would predict morbidity and
      mortality and determined whether modification would improve the predictions.
      METHODS: Patients admitted to a regional hospital with acute ICH in 1999 were
      reviewed. Independent predictors of mortality or good outcome (modified Rankin
      score <or=2) at 30 days were identified by logistic regression to devise a new
      ICH Score for comparison with the original Score. A modified Score was created by
      substituting National Institutes of Health Stroke Scale (NIHSS) for the Glasgow
      Coma Scale. RESULTS: The mortality rate was 22%, and 35% had good outcome.
      Independent factors for mortality were high NIHSS score, intraventricular
      hemorrhage, subarachnoid extension, and narrow pulse pressure. Independent
      factors for good outcome were low NIHSS score and low admission temperature. For
      all ICH Scores, no patient had a maximum score of 6. Cutoff values of >or=3 and
      <3 provided the best Youden's index of diagnostic test in all ICH Scores for
      mortality and good outcome, respectively. The original and modified ICH Scores
      predict mortality equally well. The new and modified ICH Scores are slightly
      better for prediction of good outcome. CONCLUSIONS: All 3 ICH Scores are simple
      clinical grading scales. As reliable predictors of good outcome and/or mortality,
      they are useful in clinical research studies and standardization of clinical
      protocols.

PMID- 12805489
TI  - UK-279,276, a neutrophil inhibitory glycoprotein, in acute stroke: tolerability
      and pharmacokinetics.
AB  - BACKGROUND AND PURPOSE: UK-279,276, a recombinant glycoprotein, binds selectively
      to the CD11b/CD18 integrin on neutrophils and has the potential to modulate the
      neuroinflammation associated with acute stroke. After preclinical evidence of
      neuroprotection, UK-279,276 has entered clinical development. The purposes of
      this study were to evaluate the safety and tolerability of UK-279,276 and to
      examine its pharmacokinetics and pharmacodynamics (binding to neutrophil CD11b)
      in patients with acute stroke. METHODS: This was a multicenter, double-blind,
      dose-escalation study in 176 patients randomized to a single intravenous dose of
      UK-279,276 (6 cohorts: 0.06, 0.1, 0.2, 0.5, 1.0, 1.5 mg/kg) or placebo (3:1
      randomization within each cohort) within 12 hours of stroke onset. RESULTS: Age
      and stroke severity were well balanced across groups, with a mean age of 70 years
      (range, 39 to 92 years) and moderate baseline stroke severity (mean Scandinavian
      Stroke Scale score, 36.5 to 43.2; mean National Institutes of Health Stroke Scale
      score, 6.3 to 8.5). UK-279,276 was well tolerated at doses up to 1.5 mg/kg. There
      was no evidence of a relationship between dose of UK-279,276 and adverse events
      or clinical chemistry or hematology laboratory tests, or of an increased
      incidence of infection-related adverse events with the study drug. A dose
      dependent UK-279,276-specific IgG antibody response was observed in patients
      treated with the 1.0- and 1.5-mg/kg doses. UK-279,276 displayed nonlinear
      pharmacokinetics across the dose range investigated. The duration of CD11b
      saturation was dose dependent, with >80% saturation achieved for at least 7 days
      after treatment with UK-279,276 1.0 and 1.5 mg/kg. CONCLUSIONS: UK-279,276 was
      well tolerated in acute stroke patients at single doses up to 1.5 mg/kg. Further
      clinical investigation of UK-279,276 is ongoing.

PMID- 12805490
TI  - Sex differences in first-ever acute stroke.
AB  - BACKGROUND AND PURPOSE: There are few studies analyzing stroke in women, taking
      into account the vascular risk factors, cause of stroke, clinical picture, and
      outcome. The purpose of this study was to analyze possible sex differences in
      patients suffering first-ever acute stroke. METHODS: From December 1995 to
      January 2002, 1581 patients with first-ever acute stroke were analyzed, taking
      into account sex, age, risk factors, clinical presentation, stroke subtype,
      treatment, and outcome data. RESULTS: Mean age was higher in women than in men
      (P<0.001). Hypertension (P=0.0027) and cardioembolic disease (P=0.0035) were
      independent factors related to women. Alcohol overuse (P<0.001), smoking
      (P<0.001), and vascular peripheral disease (P=0.031) were related to the male
      sex. Women more often suffered aphasic disorders (P<0.001), visual field
      disturbances (P<0.05), and dysphagia (P<0.01) than men. There were no differences
      in hemorrhagic and ischemic strokes according to sex. Women suffered more
      cardioembolic strokes (P<0.001); men suffered more atherothrombotic (P<0.001) and
      lacunar strokes (P<0.05). Women who survived remained more disabled than men
      (P<0.001). CONCLUSIONS: Sex determines some clear differences in patients
      suffering a first-ever stroke. Women were, on average, 6 years older than men and
      had a different profile of vascular risk factors and a different distribution of
      stroke subtypes. Women had a longer hospital stay and remained more disabled than
      men. The amelioration of hypertension control and increase in anticoagulant
      treatment in patients with atrial fibrillation would be the best options for
      preventing stroke, especially in women.

PMID- 12805491
TI  - Editorial comment--Thromboembolic events during neuroendovascular procedures.

PMID- 12805492
TI  - Local intra-arterial fibrinolysis of thromboemboli occurring during
      neuroendovascular procedures with recombinant tissue plasminogen activator.
AB  - BACKGROUND AND PURPOSE: There is a lack of systematic data regarding local intra
      arterial fibrinolysis (LIF) of thromboemboli occurring during neuroendovascular
      procedures with the use of recombinant tissue plasminogen activator (rtPA). We
      report our technique for treating LIF of intracerebral thromboemboli occurring
      during neuroendovascular procedures. METHODS: Nine of 723 patients (1.2%) who
      underwent neuroendovascular procedures during the period from January 1997 to
      September 2002 suffered thromboembolic complications. These patients were treated
      by LIF with a maximum dose of 0.9 mg rtPA per kilogram body weight.
      Recanalization was categorized as successful (Thrombolysis in Myocardial
      Infarction [TIMI] grade 2 or 3) versus unsuccessful (TIMI grade 0 or 1), and
      clinical outcome was categorized as independent (Rankin Scale score 0 to 2)
      versus dependent or dead (Rankin Scale score 3 to 6). RESULTS: The minimum time
      between thrombus detection and beginning of LIF was 10 minutes, and the maximum
      time was 90 minutes. Successful recanalization was achieved in 4 of 9 patients
      (44%). All 9 patients suffered cerebral ischemic infarctions, and none of the
      patients sustained intracerebral hemorrhage. Two patients (22%) died from
      malignant brain infarctions. Four patients (44%) remained moderately disabled,
      and 3 patients (33%) were severely disabled 3 months after LIF. CONCLUSIONS:
      Although we used relatively high doses of rtPA, the recanalization rates and
      clinical outcome of LIF in our patients were not satisfactory. Strategies for the
      prevention of thromboemboli during neuroendovascular procedures must be improved,
      and novel fibrinolytic or thrombolytic techniques should be developed.

PMID- 12805493
TI  - Possible role of parathyroid hormone-related protein as a proinflammatory
      cytokine in atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Parathyroid hormone-related protein (PTHrP) is a
      vasodilator peptide. In addition, PTHrP appears to affect vascular growth and to
      be a mediator of inflammation in rheumatic and brain disorders. We examined the
      possible role of PTHrP in the inflammatory process in atherosclerosis METHODS: We
      immunohistochemically analyzed the cellular localization of PTHrP, the type 1
      PTH/PTHrP receptor (PTH1R), and monocyte chemoattractant protein-1 (MCP-1) in 26
      human carotid atherosclerotic plaques. RESULTS: The inflammatory region of
      plaques was characterized by high PTHrP, PTH1R, and MCP-1 immunostaining in
      relation to the cap (0.75+/-0.1 versus 0.29+/-0.04, 0.5+/-0.1 versus 0.25+/-0.05,
      0.72+/-0.2 versus 0.29+/-0.05, respectively; P<0.05). PTHrP and MCP-1 were
      colocalized in both resident and inflammatory cells in the plaque. Moreover, in
      cultured vascular smooth muscle cells (VSMC), PTHrP(1-36) increased MCP-1 mRNA (3
      fold at 6 hours) and MCP-1 protein (2.5-fold at 24 hours). This effect was
      inhibited by either PTHrP(7-34) or various protein kinase A inhibitors and by the
      nuclear factor-kappaB (NF-kappaB) inhibitor parthenolide. Furthermore, PTHrP(1
      36) elicited an increase in NF-kappaB activation in VSMC. The 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor simvastatin inhibited the PTHrP(1
      36) induction of both NF-kappaB activity and MCP-1 overexpression, and this was
      reversed by mevalonate. CONCLUSIONS: PTHrP appears to be a novel proinflammatory
      mediator in the atheroma lesion and may contribute to the instability of carotid
      atherosclerotic plaques. Our data provide a new rationale to understand the
      mechanisms involved in the beneficial effects of statins in atherosclerosis.

PMID- 12805494
TI  - Long-term relative survival in elderly patients after carotid endarterectomy: a
      population-based study.
AB  - BACKGROUND AND PURPOSE: Octogenarians were not included in the major trials of
      carotid endarterectomy. Concern has been expressed about the role of carotid
      endarterectomy in this age group. This concern is based in part on uncertainty
      about the long-term survival of elderly patients after carotid endarterectomy.
      The aim of the present study was to assess relative survival in those patients
      >or=80 years of age undergoing carotid endarterectomy. METHODS: A population
      based record linkage study of all patients who underwent carotid endarterectomy
      from 1988 to 1998 in Western Australia was undertaken. Long-term relative
      survival after carotid endarterectomy was assessed against age- and sex-matched
      controls. RESULTS: During the period 1988 to 1998, 1796 (1306 male, 490 female)
      cases were identified. There were 151 patients >or=80 years of age. The
      cumulative survival at 5 years was 64.9% for those >or=80 years of age compared
      with 80.1% for those <80 years of age. Relative survival at 5 years was 118% (95%
      CI, 102 to 134) for those >or=80 years of age compared with 94.7% (95% CI, 92 to
      97) for those <80 years of age. CONCLUSIONS: Long-term relative survival after
      carotid endarterectomy in patients >or=80 years of age was better than that of an
      age-matched population. The likelihood of living long enough to gain benefit from
      a carotid endarterectomy is not jeopardized by being too old.

PMID- 12805495
TI  - Can patients be anticoagulated after intracerebral hemorrhage? A decision
      analysis.
AB  - BACKGROUND AND PURPOSE: Warfarin increases both the likelihood and the mortality
      of intracerebral hemorrhage (ICH), particularly in patients with a history of
      prior ICH. In light of this consideration, should a patient with both a history
      of ICH and a clear indication for anticoagulation such as nonvalvular atrial
      fibrillation be anticoagulated? In the absence of data from a clinical trial, we
      used a decision-analysis model to compare the expected values of 2 treatment
      strategies-warfarin and no anticoagulation-for such patients. METHODS: We used a
      Markov state transition decision model stratified by location of hemorrhage
      (lobar or deep hemispheric). Effectiveness was measured in quality-adjusted life
      years (QALYs). Data sources included English language literature identified
      through MEDLINE searches and bibliographies from selected articles, along with
      empirical data from our own institution. The base case focused on a 69-year-old
      man with a history of ICH and newly diagnosed nonvalvular atrial fibrillation.
      RESULTS: For patients with prior lobar ICH, withholding anticoagulation therapy
      was strongly preferred, improving quality-adjusted life expectancy by 1.9 QALYs.
      For patients with prior deep hemispheric ICH, withholding anticoagulation
      resulted in a smaller gain of 0.3 QALYs. In sensitivity analyses for patients
      with deep ICH, anticoagulation could be preferred if the risk of thromboembolic
      stroke is particularly high. CONCLUSIONS: Survivors of lobar ICH with atrial
      fibrillation should not be offered long-term anticoagulation. Similarly, most
      patients with deep hemispheric ICH and atrial fibrillation should not receive
      anticoagulant therapy. However, patients with deep hemispheric ICH at
      particularly high risk for thromboembolic stroke or low risk of ICH recurrence
      might benefit from long-term anticoagulation.

PMID- 12805496
TI  - Left ventricular hypertrophy is associated with asymptomatic cerebral damage in
      hypertensive patients.
AB  - BACKGROUND AND PURPOSE: It has been demonstrated that left ventricular
      hypertrophy (LVH) confers an increased risk for major cerebrovascular events.
      However, it is still uncertain whether there is an association between LVH and
      asymptomatic cerebrovascular damage in hypertensive patients. In this study, we
      investigated the relation between LVH, evaluated by both echocardiography (Echo
      LVH) and electrocardiography (ECG-LVH), and preclinical cerebral damage, as
      identified by magnetic resonance imaging. METHODS: One hundred ninety-five
      consecutive patients were enrolled in the study. We evaluated other risk factors
      such as age, sex, presence of diabetes, cholesterol levels, smoking status, heart
      rate, and systolic and diastolic blood pressure. Asymptomatic cerebrovascular
      damage was considered silent cerebral lesions: punctate lesions, lacunes, and
      territorial lesions. Patients were divided into 2 groups according to the
      presence of asymptomatic brain lesions. RESULTS: The 2 groups of patients
      differed only in terms of age and systolic pressure. More importantly, the
      prevalence of Echo-LVH (83% versus 47.7%, P<0.001) and ECG-LVH (56% versus 22%,
      P<0.001) was significantly higher in patients with asymptomatic brain lesions. A
      multivariate analysis allowed us to recognize LVH as the only independent
      predictor for the presence of ischemic lacunes (P<0.001). Moreover, we evaluated
      the impact of left ventricular geometry on asymptomatic cerebrovascular damage,
      and we found that hypertensives with concentric hypertrophy displayed more
      pronounced asymptomatic cerebrovascular damage compared with patients with
      eccentric hypertrophy. CONCLUSIONS: Our study demonstrates that LVH is associated
      with cerebral damage even in the absence of clinical symptoms. Thus, the presence
      of cardiac damage provides important prognostic clues about the presence of
      asymptomatic cerebral damage.

PMID- 12805497
TI  - Infection and the risk of spontaneous cervical artery dissection: a case-control
      study.
AB  - BACKGROUND AND PURPOSE: Several constitutional and environmental risk factors may
      be involved in the occurrence of spontaneous cervical artery dissection (SCAD).
      This work explored the association between recent infection and SCAD in an
      hospital-based case-control study. METHODS: Forty-seven patients with SCAD and 52
      with ischemic stroke from another cause were prospectively and consecutively
      recruited by 2 neurology departments. A specially designed questionnaire was used
      to assess the history of an acute infection that could have occurred within a
      month before the vascular event. RESULTS: Acute infection was more frequent in
      patients with SCAD (31.9%) than in control subjects (13.5%) (crude odds ratio,
      3.0; 95% confidence interval, 1.1 to 8.2; P=0.032). This association was stronger
      in patients with multiple (odds ratio, 6.4) than single artery (odds ratio, 2.1)
      dissection. CONCLUSIONS: Recent infection is a risk factor and could be a trigger
      for SCAD.

PMID- 12805498
TI  - Angiotensin-converting enzyme gene polymorphism and carotid artery wall
      thickness: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Many studies have investigated the association between
      the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D)
      polymorphism and carotid artery intima-media thickness (IMT); however, most
      studies were small and conducted in selective samples. The aim of this study was
      to evaluate this association by performing a meta-analysis on published articles.
      METHODS: We searched Medline for articles studying the association between the
      ACE I/D polymorphism and carotid IMT. Twenty-six studies were found; 23 articles
      containing 9833 subjects were qualified to enter the meta-analysis. We classified
      those articles on the basis of their samples into high-risk and low-risk
      populations and white and Asian ethnic groups. IMT was used as a continuous
      variable, and data were analyzed with the Cochrane Review Manager. RESULTS: A
      significant positive association was present between the D allele and common
      carotid IMT (weighted mean difference between DD and II genotypes, 0.23 mm x 10(
      1); P<0.01). The association was stronger among high-risk populations. The point
      estimates of DD versus II were higher than those of ID versus II. CONCLUSIONS:
      Our meta-analysis showed evidence of a positive association between the D allele
      of the ACE gene and common carotid IMT. The overall results were concordant in
      both ethnic groups.

PMID- 12805499
TI  - Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne
      Risk Factor Study (MERFS) Group.
AB  - BACKGROUND AND PURPOSE: Use of oral contraceptives has increased, and there is
      uncertainty about the stroke risk associated with their use. Our aim was to
      investigate this issue. METHODS: Using case-control techniques, we identified
      consecutive women with ischemic stroke from 4 Melbourne hospitals. All patients
      were between 15 and 55 years of age and had no prior stroke. Neighborhood-based
      control subjects were individually age-matched (+/-5 years) and geographically
      matched to subject cases. A questionnaire administered to participants elicited
      information about prior exposure to various potential risk factors, including the
      oral contraceptive pill (OCP). RESULTS: We included 234 cases and 234 controls
      (mean age, 42 years). Compared with noncurrent use, current use of the OCP, in
      doses of <or=50 microg estrogen, was not associated with an increased risk of
      ischemic stroke (odds ratio [OR] 1.76; 95% CI, 0.86 to 3.61; P=0.124). Factors
      associated with an increased risk of ischemic stroke were a history of
      hypertension (OR, 2.18; 95% CI, 1.22 to 3.91), transient ischemic attack (OR,
      8.17; 95% CI, 1.69 to 39.6), previous myocardial infarction (OR, 5.64; 95% CI,
      1.04 to 30.61), and diabetes mellitus (OR, 5.42; 95% CI, 1.42 to 20.75); family
      history of stroke (OR, 2.22; 95% CI, 1.12 to 4.43); and smoking >20 cigarettes
      per day (OR, 3.68; 95% CI, 1.22 to 11.09). CONCLUSIONS: There was no evidence for
      an association between ischemic stroke and use of the OCP in low doses (<or=50
      microg estrogen) in young Australian women. Other modifiable risk factors such as
      hypertension, diabetes mellitus, and smoking are important.

PMID- 12805500
TI  - Effects of a selective CD11b/CD18 antagonist and recombinant human tissue
      plasminogen activator treatment alone and in combination in a rat embolic model
      of stroke.
AB  - BACKGROUND AND PURPOSE: We evaluated the neuroprotective effect of UK-279,276
      (also referred to as recombinant neutrophil inhibitory factor), a selective
      CD11b/CD18 antagonist, in combination with thrombolytic therapy on focal cerebral
      ischemia. METHODS: Male Wistar rats (n=88) were subjected to embolic middle
      cerebral artery occlusion. Animals were randomly assigned to the following groups
      (n=11 in each group): vehicle treatment alone at 2 or 4 hours, UK-279,276
      treatment alone at 2 or 4 hours, recombinant human tissue plasminogen activator
      (rhtPA) treatment alone at 2 or 4 hours, or the combination of UK-279,276 and
      rhtPA at 2 or 4 hours. Infarct volume, neurological function, hemorrhagic
      transformation, neutrophil accumulation, and parenchymal fibrin deposition were
      measured 7 days after middle cerebral artery occlusion. RESULTS: Treatment with
      UK-279,276 significantly (P<0.05) improved neurological severity scores, an index
      of neurological functional deficit, but had no effect on infarct volume compared
      with vehicle-treated animals. Treatment with rhtPA alone at 2 but not 4 hours
      significantly (P<0.05) reduced infarct volume and improved neurological function
      compared with vehicle-treated animals. Combination treatment with UK-279,276 and
      rhtPA at 2 or 4 hours significantly (P<0.01) reduced infarct volume and enhanced
      recovery of neurological function compared with control. Neutrophil accumulation
      and fibrin deposition in the brain parenchyma of combination-treated rats at 2
      and 4 hours after stroke were significantly reduced (P<0.05) compared with
      corresponding vehicle-treated control groups. The neuroprotective effect of the
      combined treatments was superior to the additive effects from each treatment of
      rhtPA or UK-279,276 alone. CONCLUSIONS: These data suggest that the combination
      treatment with UK-279,276 and rhtPA may extend the window of thrombolytic therapy
      for the acute treatment of stroke.

PMID- 12805501
TI  - Editorial comment--Is there a perihematomal ischemic penumbra? More questions and
      an overlooked clue.

PMID- 12805503
TI  - Detection of hemosiderin deposition by T2*-weighted MRI after subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is very difficult to
      diagnose several months after its onset. We thus investigated subarachnoid
      hemosiderin deposition well after SAH by T2*-weighted MRI, a sensitive method for
      hemosiderin detection. METHODS: To investigate how hemosiderin deposition as
      confirmed by T2*-weighted MRI contributes to the determination of prior SAH and
      how the extent of hemosiderin deposition is associated with a number of clinical
      factors, we retrospectively analyzed 58 patients >3 months after SAH associated
      with ruptured aneurysms. We also investigated 209 healthy volunteers as controls.
      RESULTS: T2*-weighted MRI demonstrated subarachnoid hemosiderin deposition in
      72.4% of the SAH patients, whereas no deposition was seen in the healthy
      volunteer group. The hemosiderin was preferentially deposited in the subarachnoid
      space near a ruptured aneurysm. Odds ratios (ORs) were estimated from logistic
      regression analyses correlating hemosiderin deposition with other factors. Age
      (>or=54 years) (OR, 5.1; 95% CI, 1.03 to 25.0; P=0.046), Fisher grade 3 on
      initial CT (OR, 8.0; 95% CI, 1.26 to 50.4; P=0.027), and Karnofsky Scale score
      <or=80% 6 months after onset of SAH (OR, 12.8; 95% CI, 1.97 to 83.3; P=0.0077)
      were all found to be independently associated with hemosiderin deposition levels.
      CONCLUSIONS: T2*-weighted MRI is an effective means of diagnosing prior SAH and
      may also reveal the location of a ruptured aneurysm. The extent of hemosiderin
      deposition was significantly associated with several factors, including age, CT
      findings, and poor prognosis.

PMID- 12805502
TI  - Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra?
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia has been proposed as a contributing
      mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). The
      search for surrogate parameters that allow treatment stratification for
      spontaneous ICH continues. We sought to assess the presence and prognostic effect
      of perihemorrhagic ischemic changes and hypoperfusion in a prospective stroke MRI
      study. METHODS: We performed stroke MRI in 32 patients with hyperacute ICH (mean,
      16.9+/-17.2 mL) within 6 hours after symptom onset (mean, 3.1+/-1.3 hours).
      Clinical data at baseline (National Institutes of Health Stroke Scale) and on day
      90 (Barthel Index, modified Rankin Scale) were assessed. Perihemorrhagic
      perfusion- and diffusion-weighted imaging changes were assessed in a 1-cm-wide
      area around the clot. RESULTS: Despite a mild perihemorrhagic mean transit time
      prolongation of 0.7+/-1.1 second, there were no significant perihemorrhagic
      apparent diffusion coefficient or mean transit time changes indicating
      irreversible ischemia or hypoperfusion. ICH size, time to imaging, or clinical
      severity at baseline or outcome were not reflected by changes of relative
      apparent diffusion coefficient or perfusion-weighted imaging. ICH size correlated
      with baseline clinical severity (r=0.51, P=0.005). There was a significant
      association (P=0.0494) and a significant negative correlation (r=-0.468,
      P=0.0103) of perihemorrhagic perfusion change with time from symptom onset not
      associated with ICH size. CONCLUSIONS: Perihemorrhagic hypoperfusion probably is
      a consequence of reduced metabolic demand (diaschisis) rather than a sign of
      ischemia. We found no evidence for a perihemorrhagic and potentially salvageable
      ischemic penumbra in hyperacute ICH. Further studies should address metabolic,
      toxic, apoptotic, and microvascular aspects.

PMID- 12805504
TI  - Cerebral hemodynamics in asymptomatic and symptomatic patients with high-grade
      carotid stenosis undergoing carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Asymptomatic patients with carotid stenosis benefit less
      from carotid endarterectomy (CEA) than symptomatic patients because the risk of
      embolic events is lower, but it is not known whether the hemodynamic effect of
      CEA is different between the groups. We evaluated hemodynamics of symptomatic and
      asymptomatic patient groups before and after CEA. METHODS: Forty-six independent
      patients with a unilateral high-grade carotid stenosis, 23 asymptomatic and 23
      symptomatic, underwent dynamic susceptibility contrast MRI (DSC-MRI) and
      transcranial Doppler ultrasound (TCD) evaluation before CEA and 3 and 100 days
      afterward. Quantitative perfusion parameters were calculated separately in
      selected regions of white and gray matter and watershed regions in each
      hemisphere, and mean transit time (MTT) maps were assessed visually by 2
      independent observers. Vasomotor reactivity was determined with breath-holding
      index and flow impedance with pulsatility index ipsilaterally. RESULTS: In
      contrast to the asymptomatic carotid stenosis group, symptomatic carotid stenosis
      patients had preoperatively increased MTT and lower cerebral blood flow values in
      the ipsilateral hemisphere, more in white matter and watershed regions than in
      gray matter. Visually detected perfusion deficits were associated with
      symptomatic status. The interhemispheric asymmetries were abolished by CEA. The
      improving trend over time was greater in the symptomatic carotid stenosis group
      and was best seen in MTT. On TCD, pulsatility index was lower in symptomatic
      carotid stenosis patients preoperatively, with no postoperative difference,
      whereas the breath-holding index improved only in the symptomatic carotid
      stenosis group after CEA. CONCLUSIONS: Patients with asymptomatic and symptomatic
      carotid stenosis differ significantly by means of DSC-MRI and TCD before and in
      response to CEA.

PMID- 12805505
TI  - The tree of life: view from a twig.

PMID- 12805506
TI  - High-energy physics. Environmental report paralyzes Italian neutrino lab.

PMID- 12805508
TI  - U.K. science. Review gives embattled MRC a boost.

PMID- 12805507
TI  - Intellectual property. Academia gets no help from U.S. in patent case.

PMID- 12805509
TI  - Agricultural biotech. U.K. probes public opposition to GM crops.

PMID- 12805510
TI  - Germany. Retrenchment at the Max Planck Society.

PMID- 12805511
TI  - Infectious diseases. U.S. monkeypox outbreak traced to Wisconsin pet dealer.

PMID- 12805512
TI  - Paleoanthropology. Oldest members of Homo sapiens discovered in Africa.

PMID- 12805514
TI  - Iran's nuclear program. State-of-the-art nuclear sleuths.

PMID- 12805513
TI  - Iran's nuclear program. Another Middle East showdown.

PMID- 12805515
TI  - Conservation biology. Can great apes be saved from Ebola?

PMID- 12805516
TI  - Molecular biology. Spinning junk into gold.

PMID- 12805517
TI  - Anthropology. Cracking the khipu code.

PMID- 12805518
TI  - Retraction.

PMID- 12805519
TI  - Larvae retention: genes or oceanography?

PMID- 12805520
TI  - Clarifying standards for using placebos.

PMID- 12805521
TI  - Comment on "Separate evolutionary origins of teeth from evidence in fossil jawed
      vertebrates".

PMID- 12805523
TI  - Genetics. Poultry genetic resources--operation rescue needed.

PMID- 12805524
TI  - Genetics. Chicken genome--science nuggets to come soon.

PMID- 12805525
TI  - Virology. Picking the right spot.

PMID- 12805526
TI  - Physics. How to freeze out collisions.

PMID- 12805527
TI  - Psychology and economics. Strategizing in the brain.

PMID- 12805528
TI  - Cell biology. Persistence pays.

PMID- 12805529
TI  - Climate change. A guide to CO2 sequestration.

PMID- 12805530
TI  - Presidential address. Science as a way of life: perplexities of a physician
      scientist.

PMID- 12805532
TI  - Modernizing the tree of life.

PMID- 12805533
TI  - Drafting a tree.

PMID- 12805534
TI  - Plants find their places on the tree of life.

PMID- 12805535
TI  - Dating the tree of life.
AB  - The relative merits of molecular and paleontological dates of major branching
      points in the tree of life are currently debated. In some cases, molecular date
      estimates are up to twice as old as paleontological dates. However, although it
      is true that paleontological dates are often too young (missing fossils),
      molecular dates are often too old (statistical bias). Intense study of the dating
      of major splits in the tree of mammals has shown rapprochement as fossil dates
      become older and molecular dates become younger.

PMID- 12805536
TI  - Evolution of the protein repertoire.
AB  - Most proteins have been formed by gene duplication, recombination, and
      divergence. Proteins of known structure can be matched to about 50% of genome
      sequences, and these data provide a quantitative description and can suggest
      hypotheses about the origins of these processes.

PMID- 12805537
TI  - The deep roots of eukaryotes.
AB  - Most cultivated and characterized eukaryotes can be confidently assigned to one
      of eight major groups. After a few false starts, we are beginning to resolve
      relationships among these major groups as well. However, recent developments are
      radically revising this picture again, particularly (i) the discovery of the
      likely antiquity and taxonomic diversity of ultrasmall eukaryotes, and (ii) a
      fundamental rethinking of the position of the root. Together these data suggest
      major gaps in our understanding simply of what eukaryotes are or, when it comes
      to the tree, even which end is up.

PMID- 12805538
TI  - Phylogenomics: intersection of evolution and genomics.
AB  - Much has been gained from genomic and evolutionary studies of species. Combining
      the perspectives of these different approaches suggests that an integrated
      phylogenomic approach will be beneficial.

PMID- 12805539
TI  - Preserving the tree of life.
AB  - Phylogenies provide new ways to measure biodiversity, to assess conservation
      priorities, and to quantify the evolutionary history in any set of species.
      Methodological problems and a lack of knowledge about most species have so far
      hampered their use. In the future, as techniques improve and more data become
      accessible, we will have an expanded set of conservation options, including ways
      to prioritize outcomes from evolutionary and ecological processes.

PMID- 12805540
TI  - Hybrid origin of SIV in chimpanzees.

PMID- 12805541
TI  - Selective charging of tRNA isoacceptors explains patterns of codon usage.
AB  - We modeled how the charged levels of different transfer RNAs (tRNAs) that carry
      the same amino acid (isoacceptors) respond when this amino acid becomes growth
      limiting. The charged levels will approach zero for some isoacceptors (such as
      tRNA2Leu) and remain high for others (such as tRNA4Leu), as determined by the
      concentrations of isoacceptors and how often their codons occur in protein
      synthesis. The theory accounts for (synonymous) codons for the same amino acid
      that are used in ribosome-mediated transcriptional attenuation, the choices of
      synonymous codons in trans-translating transfermessenger RNA, and the
      overrepresentation of rare codons in messenger RNAs for amino acid biosynthetic
      enzymes.

PMID- 12805542
TI  - The interface phase and the Schottky barrier for a crystalline dielectric on
      silicon.
AB  - The barrier height for electron exchange at a dielectric-semiconductor interface
      has long been interpreted in terms of Schottky's theory with modifications from
      gap states induced in the semiconductor by the bulk termination. Rather, we show
      with the structure specifics of heteroepitaxy that the electrostatic boundary
      conditions can be set in a distinct interface phase that acts as a "Coulomb
      buffer." This Coulomb buffer is tunable and will functionalize the barrier-height
      concept itself.

PMID- 12805543
TI  - Interference of quantized transition-state pathways in the H + D2 -> D + HD
      chemical reaction.
AB  - The collision-energy dependence of the state-resolved differential cross section
      at a specific backward-scattering angle for the reaction H + D2 --> D + HD is
      measured with the D-atom Rydberg "tagging" time-of-flight technique. The reaction
      was modeled theoretically with converged quantum scattering calculations that
      provided physical interpretation of the observations. Oscillations in the
      differential cross sections in the backward-scattering direction are clearly
      observed and are attributed to the transition-state structures that originate
      from the interferences of different quantized transition-state pathways.

PMID- 12805544
TI  - Impact ejecta layer from the mid-Devonian: possible connection to global mass
      extinctions.
AB  - We have found evidence for a bolide impacting Earth in the mid-Devonian (
      approximately 380 million years ago), including high concentrations of shocked
      quartz, Ni, Cr, As, V, and Co anomalies; a large negative carbon isotope shift (
      9 per mil); and microspherules and microcrysts at Jebel Mech Irdane in the Anti
      Atlas desert near Rissani, Morocco. This impact is important because it is
      coincident with a major global extinction event (Kacak/otomari event), suggesting
      a possible cause-and-effect relation between the impact and the extinction. The
      result may represent the extinction of as many as 40% of all living marine animal
      genera.

PMID- 12805545
TI  - Holocene forcing of the Indian monsoon recorded in a stalagmite from southern
      Oman.
AB  - A high-resolution oxygen-isotope record from a thorium-uranium-dated stalagmite
      from southern Oman reflects variations in the amount of monsoon precipitation for
      the periods from 10.3 to 2.7 and 1.4 to 0.4 thousand years before the present (ky
      B.P.). Between 10.3 and 8 ky B.P., decadal to centennial variations in monsoon
      precipitation are in phase with temperature fluctuations recorded in Greenland
      ice cores, indicating that early Holocene monsoon intensity is largely controlled
      by glacial boundary conditions. After approximately 8 ky B.P., monsoon
      precipitation decreases gradually in response to changing Northern Hemisphere
      summer solar insolation, with decadal to multidecadal variations in monsoon
      precipitation being linked to solar activity.

PMID- 12805546
TI  - Potential environmental impact of a hydrogen economy on the stratosphere.
AB  - The widespread use of hydrogen fuel cells could have hitherto unknown
      environmental impacts due to unintended emissions of molecular hydrogen,
      including an increase in the abundance of water vapor in the stratosphere
      (plausibly by as much as approximately 1 part per million by volume). This would
      cause stratospheric cooling, enhancement of the heterogeneous chemistry that
      destroys ozone, an increase in noctilucent clouds, and changes in tropospheric
      chemistry and atmosphere-biosphere interactions.

PMID- 12805547
TI  - Sex-dependent gene expression and evolution of the Drosophila transcriptome.
AB  - Comparison of the gene-expression profiles between adults of Drosophila
      melanogaster and Drosophila simulans has uncovered the evolution of genes that
      exhibit sex-dependent regulation. Approximately half the genes showed differences
      in expression between the species, and among these, approximately 83% involved a
      gain, loss, increase, decrease, or reversal of sex-biased expression. Most of the
      interspecific differences in messenger RNA abundance affect male-biased genes.
      Genes that differ in expression between the species showed functional clustering
      only if they were sex-biased. Our results suggest that sex-dependent selection
      may drive changes in expression of many of the most rapidly evolving genes in the
      Drosophila transcriptome.

PMID- 12805548
TI  - Fusion of cells by flipped SNAREs.
AB  - The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)
      hypothesis suggests that pairs of proteins known as vesicle (v-) SNAREs and
      target membrane (t-) SNAREs interact specifically to control and mediate
      intracellular membrane fusion events. Here, cells expressing the interacting
      domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously,
      demonstrating that SNAREs are sufficient to fuse biological membranes.

PMID- 12805549
TI  - Transcription start regions in the human genome are favored targets for MLV
      integration.
AB  - Factors contributing to retroviral integration have been intractable because past
      studies have not precisely located genomic sites of proviruses in sufficient
      numbers for significant analysis. In this study, 903 murine leukemia virus (MLV)
      and 379 human immunodeficiency virus-1 (HIV-1) integrations in the human genome
      were mapped. The data showed that MLV preferred integration near the start of
      transcriptional units (either upstream or downstream) whereas HIV-1 preferred
      integration anywhere in the transcriptional unit but not upstream of the
      transcriptional start. Defining different integration site preferences for
      retroviruses will have important ramifications for gene therapy and may aid in
      our understanding of the factors directing the integration process.

PMID- 12805550
TI  - Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term
      depression.
AB  - Cerebellar long-term depression (LTD) is a model of synaptic memory that requires
      protein kinase C (PKC) activation and is expressed as a reduction in the number
      of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice
      lacking the AMPA receptor GluR2 subunit and could be rescued by transient
      transfection with the wild-type GluR2 subunit. Transfection with a point mutant
      that eliminated PKC phosphorylation of Ser880 in the carboxy-terminal PDZ ligand
      of GluR2 failed to restore LTD. In contrast, transfection with a point mutant
      that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC
      phosphorylation of GluR2 Ser880 is a critical event in the induction of
      cerebellar LTD.

PMID- 12805551
TI  - The neural basis of economic decision-making in the Ultimatum Game.
AB  - The nascent field of neuroeconomics seeks to ground economic decision making in
      the biological substrate of the brain. We used functional magnetic resonance
      imaging of Ultimatum Game players to investigate neural substrates of cognitive
      and emotional processes involved in economic decision-making. In this game, two
      players split a sum of money;one player proposes a division and the other can
      accept or reject this. We scanned players as they responded to fair and unfair
      proposals. Unfair offers elicited activity in brain areas related to both emotion
      (anterior insula) and cognition (dorsolateral prefrontal cortex). Further,
      significantly heightened activity in anterior insula for rejected unfair offers
      suggests an important role for emotions in decision-making.

PMID- 12805552
TI  - V1 neurons signal acquisition of an internal representation of stimulus location.
AB  - A fundamental aspect of visuomotor behavior is deciding where to look or move
      next. Under certain conditions, the brain constructs an internal representation
      of stimulus location on the basis of previous knowledge and uses it to move the
      eyes or to make other movements. Neuronal responses in primary visual cortex were
      modulated when such an internal representation was acquired: Responses to a
      stimulus were affected progressively by sequential presentation of the stimulus
      at one location but not when the location was varied randomly. Responses of
      individual neurons were spatially tuned for gaze direction and tracked the
      Bayesian probability of stimulus appearance. We propose that the representation
      arises in a distributed cortical network and is associated with systematic
      changes in response selectivity and dynamics at the earliest stages of cortical
      visual processing.

PMID- 12805553
TI  - NompC TRP channel required for vertebrate sensory hair cell mechanotransduction.
AB  - The senses of hearing and balance in vertebrates rely on the sensory hair cells
      (HCs) of the inner ear. The central element of the HC's transduction apparatus is
      a mechanically gated ion channel of unknown identity. Here we report that the
      zebrafish ortholog of Drosophila no mechanoreceptor potential C (nompC), which
      encodes a transient receptor potential (TRP) channel, is critical for HC
      mechanotransduction. In zebrafish larvae, nompC is selectively expressed in
      sensory HCs. Morpholino-mediated removal of nompC function eliminated
      transduction-dependent endocytosis and electrical responses in HCs, resulting in
      larval deafness and imbalance. These observations indicate that nompC encodes a
      vertebrate HC mechanotransduction channel.

PMID- 12805554
TI  - Comprehensive identification of human bZIP interactions with coiled-coil arrays.
AB  - In eukaryotes, the combinatorial association of sequence-specific DNA binding
      proteins is essential for transcription. We have used protein arrays to test 492
      pairings of a nearly complete set of coiled-coil strands from human basic-region
      leucine zipper (bZIP) transcription factors. We find considerable partnering
      selectivity despite the bZIPs' homologous sequences. The interaction data are of
      high quality, as assessed by their reproducibility, reciprocity, and agreement
      with previous observations. Biophysical studies in solution support the relative
      binding strengths observed with the arrays. New associations provide insights
      into the circadian clock and the unfolded protein response.

PMID- 12805555
TI  - Estimating the rock volume bias in paleobiodiversity studies.
AB  - To interpret changes in biodiversity through geological time, it is necessary
      first to correct for biases in sampling effort related to variations in the
      exposure of rocks and recovery of fossils with age. Data from New Zealand
      indicate that outcrop area is likely to be a reliable proxy of rock volume in
      both stable cratonic regions, where the paleobiodiversity record is strongly
      correlated with relative sea level, and on tectonically active margins. In
      contrast, another potential proxy, the number of rock formations, is a poor
      predictor of outcrop area or sampling effort in the New Zealand case.

PMID- 12805556
TI  - Paleontology. Making the best of a patchy fossil record.

PMID- 12805557
TI  - Thin-section CT in patients with severe acute respiratory syndrome following
      hospital discharge: preliminary experience.
AB  - PURPOSE: To report the initial experience regarding thin-section computed
      tomographic (CT) findings in patients with severe acute respiratory syndrome
      (SARS) who improved clinically after treatment. MATERIALS AND METHODS: Twenty
      four patients (10 men, 14 women; mean age, 39 years; age range, 23-70 years) with
      confirmed SARS underwent follow-up thin-section CT of the thorax. The scans were
      obtained on average 36.5 days after hospital admission and were analyzed for
      parenchymal abnormality (ground-glass opacification, consolidation, or
      interstitial thickening) and evidence of fibrosis (parenchymal band, traction
      bronchiectasis, irregular interfaces). Patients were assigned to group 1 (with CT
      evidence of fibrosis) and group 2 (without CT evidence of fibrosis) for analysis.
      Patient demographics, length of hospital stay, rate of intensive care unit
      admission, peak lactate dehydrogenase level, pulsed intravenous
      methylprednisolone therapy, and peak opacification on chest radiographs were
      compared between the two groups. RESULTS: Parenchymal abnormality was found in
      96% (23 of 24) of patients and ranged from residual ground-glass opacification
      and interstitial thickening in group 2 (nine of 24, 38%) to fibrosis in group 1
      (15 of 24, 62%). Patients in group 1 were older (mean age, 45 vs 30.3 years), had
      a higher rate of intensive care unit admission (27% [four of 15] vs 11% [one of
      nine]), more requirement for pulsed intravenous methylprednisolone (87%, [13 of
      15] vs 67% [six of nine]), higher peak lactate dehydrogenase level (438.9 vs
      355.6 U/L), and higher peak opacification on chest radiographs (estimated area,
      14% vs 11%) than patients in group 2. CONCLUSION: Pulmonary fibrosis may develop
      early in patients with SARS who have been discharged after treatment. Patients
      who are older and have more severe disease during treatment are more likely to
      develop thin-section CT findings of fibrosis.

PMID- 12805558
TI  - Detailed map of a cis-regulatory input function.
AB  - Most genes are regulated by multiple transcription factors that bind specific
      sites in DNA regulatory regions. These cis-regulatory regions perform a
      computation: the rate of transcription is a function of the active concentrations
      of each of the input transcription factors. Here, we used accurate gene
      expression measurements from living cell cultures, bearing GFP reporters, to map
      in detail the input function of the classic lacZYA operon of Escherichia coli, as
      a function of about a hundred combinations of its two inducers, cAMP and
      isopropyl beta-d-thiogalactoside (IPTG). We found an unexpectedly intricate
      function with four plateau levels and four thresholds. This result compares well
      with a mathematical model of the binding of the regulatory proteins cAMP receptor
      protein (CRP) and LacI to the lac regulatory region. The model is also used to
      demonstrate that with few mutations, the same region could encode much purer AND
      like or even OR-like functions. This possibility means that the wild-type region
      is selected to perform an elaborate computation in setting the transcription
      rate. The present approach can be generally used to map the input functions of
      other genes.

PMID- 12805559
TI  - CD40 ligand is a critical effector of Epstein-Barr virus in host cell survival
      and transformation.
AB  - Epstein-Barr virus (EBV), implicated in numerous human diseases, including
      lymphoid malignancies, persistently infects peripheral B cells and transforms
      them into lymphoblastoid cell lines. Here we found that EBV equally infected B
      cells from patients with X-linked hyper IgM syndrome and those from healthy
      donors; however, it hardly transformed X-linked hyper IgM syndrome B cells,
      because of the dysfunctional gene of CD40 ligand (CD40L) of the patients. Unlike
      CD40, CD40L is not usually expressed on B cells. However, we found that EBV
      infection of normal B cells induced CD40L expression as a critical effector in
      host cell transformation and survival. Moreover, chronic active EBV infection of
      peripheral T cells, implicated in T cell malignancies, was associated with
      ectopic expression of CD40, and, in Jurkat T cells, EBV infection induced CD40
      expression. These results suggest that EBV infection induces CD40L/CD40 signaling
      in host cells, which appears to play an essential role in its persistent
      infection and malignancies of lymphocytes.

PMID- 12805560
TI  - Mapping of quantitative trait loci controlling trypanotolerance in a cross of
      tolerant West African N'Dama and susceptible East African Boran cattle.
AB  - Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock
      productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL)
      controlling resistance to trypanosomosis in cattle, an experimental cross was
      made between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptible
      improved Kenya Boran (Bos indicus) cattle. Sixteen phenotypic traits were defined
      describing anemia, body weight, and parasitemia. One hundred seventy-seven F2
      animals and their parents and grandparents were genotyped at 477 molecular marker
      loci covering all 29 cattle autosomes. Total genome coverage was 82%. Putative
      QTL were mapped to 18 autosomes at a genomewise false discovery rate of <0.20.
      The results are consistent with a single QTL on 17 chromosomes and two QTL on
      BTA16. Individual QTL effects ranged from approximately 6% to 20% of the
      phenotypic variance of the trait. Excluding chromosomes with ambiguous or
      nontrypanotolerance effects, the allele for resistance to trypanosomosis
      originated from the N'Dama parent at nine QTL and from the Kenya Boran at five
      QTL, and at four QTL there is evidence of an overdominant mode of inheritance.
      These results suggest that selection for trypanotolerance within an F2 cross
      between N'Dama and Boran cattle could produce a synthetic breed with higher
      trypanotolerance levels than currently exist in the parental breeds.

PMID- 12805561
TI  - Myoblasts transplanted into rat infarcted myocardium are functionally isolated
      from their host.
AB  - Survival and differentiation of myogenic cells grafted into infarcted myocardium
      have raised the hope that cell transplantation becomes a new therapy for
      cardiovascular diseases. The approach was further supported by transplantation of
      skeletal myoblasts, which was shown to improve cardiac performance in several
      animal species. Despite the success of myoblast transplantation and its recent
      trial in human, the mechanism responsible for the functional improvement remains
      unclear. Here, we used intracellular recordings coupled to video and fluorescence
      microscopy to establish whether myoblasts, genetically labeled with enhanced GFP
      and transplanted into rat infarcted myocardium, retain excitable and contractile
      properties, and participate actively to cardiac function. Our results indicate
      that grafted myoblasts differentiate into peculiar hyperexcitable myotubes with a
      contractile activity fully independent of neighboring cardiomyocytes. We conclude
      that mechanisms other than electromechanical coupling between grafted and host
      cells are involved in the improvement of cardiac function.

PMID- 12805562
TI  - Evidence that mouse brain neuropathy target esterase is a lysophospholipase.
AB  - Neuropathy target esterase (NTE) is inhibited by several organophosphorus (OP)
      pesticides, chemical warfare agents, lubricants, and plasticizers, leading to OP
      induced delayed neuropathy in people (>30,000 cases of human paralysis) and hens
      (the best animal model for this demyelinating disease). The active site region of
      NTE as a recombinant protein preferentially hydrolyzes lysolecithin, suggesting
      that this enzyme may be a type of lysophospholipase (LysoPLA) with lysolecithin
      as its physiological substrate. This hypothesis is tested here in mouse brain by
      replacing the phenyl valerate substrate of the standard NTE assay with
      lysolecithin for an "NTE-LysoPLA" assay with four important findings. First, NTE
      LysoPLA activity, as the NTE activity, is 41-45% lower in Nte-haploinsufficient
      transgenic mice than in their wild-type littermates. Second, the potency of six
      delayed neurotoxicants or toxicants as in vitro inhibitors varies from IC50 0.02
      to 13,000 nM and is essentially the same for NTE-LysoPLA and NTE (r2 = 0.98).
      Third, the same six delayed toxicants administered i.p. to mice at multiple doses
      inhibit brain NTE-LysoPLA and NTE to the same extent (r2 = 0.90). Finally, their
      in vivo inhibition of brain NTE-LysoPLA generally correlates with delayed
      toxicity. Therefore, OP-induced delayed toxicity in mice, and possibly the
      hyperactivity associated with NTE deficiency, may be due to NTE-LysoPLA
      inhibition, leading to localized accumulation of lysolecithin, a known
      demyelinating agent and receptor-mediated signal transducer. This mouse model has
      some features in common with OP-induced delayed neuropathy in hens and people but
      differs in the neuropathological signs and apparently the requirement for NTE
      aging.

PMID- 12805563
TI  - The interplay of glycosylation and disulfide formation influences fibrillization
      in a prion protein fragment.
AB  - It is now accepted that the structural transition from cellular prion protein
      (PrPC) to proteinase K-resistant prion protein scrapie (PrPSc) is the major event
      leading to transmissible spongiform encephalopathies. Although the mechanism of
      this transition remains elusive, glycosylation has been proposed to impede the
      PrPC to PrPSc conversion. To address the role of glycosylation, we have prepared
      glycosylated and unglycosylated peptides derived from the 175-195 fragment of the
      human prion protein. Comparison of the structure, aggregation kinetics, fibril
      formation capabilities, and redox susceptibility of Cys-179 has shown that the N
      linked glycan (at Asn-181) significantly reduces the rate of fibrillization by
      promoting intermolecular disulfide formation via Cys-179. Further-more, the
      aggressive fibrillization of a C179S mutant of this fragment highlights the
      significant role of disulfide stability in retarding the rate of fibril
      formation. The implications of these studies are discussed in the context of
      fibril formation in the intact prion protein.

PMID- 12805564
TI  - Blockade of advanced glycation end-product formation restores ischemia-induced
      angiogenesis in diabetic mice.
AB  - We hypothesized that formation of advanced glycation end products (AGEs)
      associated with diabetes reduces matrix degradation by metalloproteinases (MMPs)
      and contributes to the impairment of ischemia-induced angiogenesis. Mice were
      treated or not with streptozotocin (40 mg/kg) and streptozotocin plus
      aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment,
      hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels
      were strongly elevated in diabetic mice when compared with control mice (579 +/-
      21 versus 47 +/- 4 pmol/ml, respectively; P < 0.01). Treatment with
      aminoguanidine reduced AGE plasma levels when compared with untreated diabetic
      mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg
      angiographic score, capillary density, and laser Doppler skin-perfusion ratios
      were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls
      (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced
      angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE
      formation-induced hampered neovascularization process. After 3 days of ischemia,
      MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated
      and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05).
      Despite this activation of the MMP pathway, collagenolysis was decreased in
      untreated diabetic mice. Conversely, treatment of diabetic mice with
      aminoguanidine restored collagenolysis toward levels found in control mice. In
      conclusion, blockade of AGE formation by aminoguanidine normalizes impaired
      ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated
      by restoration of matrix degradation processes that are disturbed as a result of
      AGE accumulation.

PMID- 12805565
TI  - The coiled-coil of the human Rad50 DNA repair protein contains specific segments
      of increased flexibility.
AB  - Protein structural features are usually determined by defining regularities in a
      large population of homogeneous molecules. However, irregular features such as
      structural variation and flexibility are likely to be missed, despite their vital
      role for their biological function. In this paper, we report the observation of
      striking irregularities in the flexibility of the coiled-coil region of the human
      Rad50 DNA repair protein. Existing methods to quantitatively analyze flexibility
      are applicable to homogeneous polymers only. Because protein coiled-coils cannot
      be assumed to be homogeneous, we develop a method to quantify the local
      flexibility from high-resolution atomic force microscopy images. Indeed, in Rad50
      coiled-coils, two positions of increased flexibility are observed. We discuss how
      this dynamic structural feature is integral to Rad50 function.

PMID- 12805566
TI  - Fast gating in the Shaker K+ channel and the energy landscape of activation.
AB  - An early component of the gating current in Shaker K+ channels with a time
      constant of approximately 12 microsec has been recorded with a high-speed patch
      clamp setup. This fast component was found to be part of the gating current
      associated with the opening and closing of the channel. With regard to an energy
      landscape interpretation of protein kinetics, the voltage and temperature
      dependence of the fast component may be explained by a combination of drift
      diffusion and barrier jumping in the initial stages of channel activation. The
      data were modeled by a gating particle undergoing Brownian motion in a one
      dimensional diffusion landscape that featured diminishing electrical resistance
      and entropy in the direction of channel activation. The final open state of the
      channel was reasoned to be narrow and deep to account for successful subtraction
      of linear-charge displacements at positive potentials. The overall picture of
      gating that emerges from these studies is that the channel experiences
      incremental organization from a relaxed state in the early steps of activation to
      a rigidly structured open state.

PMID- 12805567
TI  - Tetraspanin CD151 regulates alpha6beta1 integrin adhesion strengthening.
AB  - The tetraspanin CD151 molecule associates specifically with laminin-binding
      integrins, including alpha6beta1. To probe strength of alpha6beta1-dependent
      adhesion to laminin-1, defined forces (0-1.5 nN) were applied to magnetic laminin
      coated microbeads bound to NIH 3T3 cells. For NIH 3T3 cells bearing wild-type
      CD151, adhesion strengthening was observed, as bead detachment became more
      difficult over time. In contrast, mutant CD151 (with the C-terminal region
      replaced) showed impaired adhesion strengthening. Static cell adhesion to laminin
      1, and detachment of beads coated with fibronectin or anti-alpha6 antibody were
      all unaffected by CD151 mutation. Hence, CD151 plays a key role in selectively
      strengthening alpha6beta1 integrin-mediated adhesion to laminin-1.

PMID- 12805568
TI  - Regression of established tumors and metastases by potent vascular endothelial
      growth factor blockade.
AB  - Vascular endothelial growth factor (VEGF) is a critical promoter of blood vessel
      growth during embryonic development and tumorigenesis. To date, studies of VEGF
      antagonists have primarily focused on halting progression in models of minimal
      residual cancer. Consistent with this focus, recent clinical trials suggest that
      blockade of VEGF may impede cancer progression, presumably by preventing
      neoangiogenesis. However, VEGF is also a key mediator of endothelial-vascular
      mural cell interactions, a role that may contribute to the integrity of mature
      vessels in advanced tumors. Here, we report that high-affinity blockade of VEGF,
      using the recently described VEGF-Trap, abolishes mature, preexisting vasculature
      in established xenografts. Eradication of vasculature is followed by marked tumor
      regression, including regression of lung micrometastases. Thus, the contribution
      of relatively low levels of VEGF to vessel integrity may be critical to
      maintenance of even very small tumor masses. Potent blockade of VEGF may provide
      a new therapeutic option for patients with bulky, metastatic cancers.

PMID- 12805570
TI  - Towards a modeling infrastructure for studying plant cells.

PMID- 12805571
TI  - Plant systems biology: lessons from a fruitful collaboration.

PMID- 12805572
TI  - Attacking complex problems with the power of systems biology.

PMID- 12805573
TI  - Predictive metabolic engineering: a goal for systems biology.

PMID- 12805574
TI  - A systems approach to the COP9 signalosome.

PMID- 12805575
TI  - Frontiers of plant cell biology: signals and pathways, system-based approaches
      22nd Symposium in Plant Biology (University of California--Riverside).

PMID- 12805576
TI  - Building integrated models of plant growth and development.

PMID- 12805577
TI  - Light- and carbon-signaling pathways. Modeling circuits of interactions.
AB  - Here, we report the systematic exploration and modeling of interactions between
      light and sugar signaling. The data set analyzed explores the interactions of
      sugar (sucrose) with distinct light qualities (white, blue, red, and far-red)
      used at different fluence rates (low or high) in etiolated seedlings and mature
      green plants. Boolean logic was used to model the effect of these carbon/light
      interactions on three target genes involved in nitrogen assimilation: asparagine
      synthetase (ASN1 and ASN2) and glutamine synthetase (GLN2). This analysis enabled
      us to assess the effects of carbon on light-induced genes (GLN2/ASN2) versus
      light-repressed genes (ASN1) in this pathway. New interactions between carbon and
      blue-light signaling were discovered, and further connections between red/far-red
      light and carbon were modeled. Overall, light was able to override carbon as a
      major regulator of ASN1 and GLN2 in etiolated seedlings. By contrast, carbon
      overrides light as the major regulator of GLN2 and ASN2 in light-grown plants.
      Specific examples include the following: Carbon attenuated the blue-light
      induction of GLN2 in etiolated seedlings and also attenuated the white-, blue-,
      and red-light induction of GLN2 and ASN2 in light-grown plants. By contrast,
      carbon potentiated far-red-light induction of GLN2 and ASN2 in light-grown
      plants. Depending on the fluence rate of far-red light, carbon either attenuated
      or potentiated light repression of ASN1 in light-grown plants. These studies
      indicate the interaction of carbon with blue, red, and far-red-light signaling
      and set the stage for further investigation into modeling this complex web of
      interacting pathways using systems biology approaches.

PMID- 12805578
TI  - AraCyc: a biochemical pathway database for Arabidopsis.
AB  - AraCyc is a database containing biochemical pathways of Arabidopsis, developed at
      The Arabidopsis Information Resource (http://www.arabidopsis.org). The aim of
      AraCyc is to represent Arabidopsis metabolism as completely as possible with a
      user-friendly Web-based interface. It presently features more than 170 pathways
      that include information on compounds, intermediates, cofactors, reactions,
      genes, proteins, and protein subcellular locations. The database uses Pathway
      Tools software, which allows the users to visualize a bird's eye view of all
      pathways in the database down to the individual chemical structures of the
      compounds. The database was built using Pathway Tools' Pathologic module with
      MetaCyc, a collection of pathways from more than 150 species, as a reference
      database. This initial build was manually refined and annotated. More than 20
      plant-specific pathways, including carotenoid, brassinosteroid, and gibberellin
      biosyntheses have been added from the literature. A list of more than 40 plant
      pathways will be added in the coming months. The quality of the initial,
      automatic build of the database was compared with the manually improved version,
      and with EcoCyc, an Escherichia coli database using the same software system that
      has been manually annotated for many years. In addition, a Perl interface,
      PerlCyc, was developed that allows programmers to access Pathway Tools databases
      from the popular Perl language. AraCyc is available at the tools section of The
      Arabidopsis Information Resource Web site
      (http://www.arabidopsis.org/tools/aracyc).

PMID- 12805579
TI  - Annotation of the Arabidopsis genome.

PMID- 12805580
TI  - Refined annotation of the Arabidopsis genome by complete expressed sequence tag
      mapping.
AB  - Expressed sequence tags (ESTs) currently encompass more entries in the public
      databases than any other form of sequence data. Thus, EST data sets provide a
      vast resource for gene identification and expression profiling. We have mapped
      the complete set of 176,915 publicly available Arabidopsis EST sequences onto the
      Arabidopsis genome using GeneSeqer, a spliced alignment program incorporating
      sequence similarity and splice site scoring. About 96% of the available ESTs
      could be properly aligned with a genomic locus, with the remaining ESTs deriving
      from organelle genomes and non-Arabidopsis sources or displaying insufficient
      sequence quality for alignment. The mapping provides verified sets of EST
      clusters for evaluation of EST clustering programs. Analysis of the spliced
      alignments suggests corrections to current gene structure annotation and provides
      examples of alternative and non-canonical pre-mRNA splicing. All results of this
      study were parsed into a database and are accessible via a flexible Web interface
      at http://www.plantgdb.org/AtGDB/.

PMID- 12805581
TI  - Rapid, noninvasive screening for perturbations of metabolism and plant growth
      using chlorophyll fluorescence imaging.
AB  - A rapid, noninvasive technique involving imaging of chlorophyll fluorescence
      parameters for detecting perturbations of leaf metabolism and growth in seedlings
      is described. Arabidopsis seedlings were grown in 96-well microtitre plates for 4
      d and then treated with eight herbicides with differing modes of action to induce
      perturbations in a range of different metabolic processes. Imaging of chlorophyll
      fluorescence emissions from 96 seedlings growing on a microtitre plate enabled
      images of a number of fluorescence parameters to be rapidly and simultaneously
      produced for the plants in each well. Herbicideinduced perturbations in
      metabolism, even in metabolic reactions not directly associated with
      photosynthetic metabolism, were detected from the changes in the images of
      fluorescence parameters considerably before any visual effects on seedling growth
      were observed. Evaluations of seedling growth were made from measurements of the
      area of chlorophyll fluorescence emission in images of plants growing in the 96
      well plates. Decreased seedling growth related directly to herbicideinduced
      changes in the imaged chlorophyll fluorescence parameters. The applicability of
      this rapid-screening technique for metabolic perturbations in monocotyledonous
      species was demonstrated by treating Agrostis tenuis seedlings with Imazapyr, an
      inhibitor of branched-chain amino acid synthesis.

PMID- 12805582
TI  - Identification of Arabidopsis rat mutants.
AB  - Limited knowledge currently exists regarding the roles of plant genes and
      proteins in the Agrobacterium tumefaciens-mediated transformation process. To
      understand the host contribution to transformation, we carried out root-based
      transformation assays to identify Arabidopsis mutants that are resistant to
      Agrobacterium transformation (rat mutants). To date, we have identified 126 rat
      mutants by screening libraries of T-DNA insertion mutants and by using various
      "reverse genetic" approaches. These mutants disrupt expression of genes of
      numerous categories, including chromatin structural and remodeling genes, and
      genes encoding proteins implicated in nuclear targeting, cell wall structure and
      metabolism, cytoskeleton structure and function, and signal transduction. Here,
      we present an update on the identification and characterization of these rat
      mutants.

PMID- 12805583
TI  - A resource of mapped dissociation launch pads for targeted insertional
      mutagenesis in the Arabidopsis genome.
AB  - We describe a new resource for targeted insertional mutagenesis in Arabidopsis
      using a maize (Zea mays) Activator/Dissociation (Ds) two-element system. The two
      components of the system, T-DNA vectors carrying a Ds launch pad and a stable
      Activator transposase source, were designed to simplify selection of
      transposition events and maximize their usefulness. Because Ds elements
      preferentially transpose to nearby genomic sites, they can be used in targeted
      mutagenesis of linked genes. To efficiently target all genes throughout the
      genome, we generated a large population of transgenic Arabidopsis plants
      containing the Ds launch pad construct, identified lines containing single Ds
      launch pad inserts, and mapped the positions of Ds launch pads in 89 lines. The
      integration sites of the Ds launch pads were relatively evenly distributed on all
      five chromosomes, except for a region of chromosomes 2 and 4 and the centromeric
      regions. This resource therefore provides access to the majority of the
      Arabidopsis genome for targeted tagging.

PMID- 12805584
TI  - Use of serial analysis of gene expression technology to reveal changes in gene
      expression in Arabidopsis pollen undergoing cold stress.
AB  - We have characterized the global gene expression patterns of Arabidopsis pollen
      using Serial Analysis of Gene Expression (SAGE). A total of 21,237 SAGE tags were
      sequenced and 4,211 unique tags were identified. Interestingly, the number of
      unique tags in pollen was low compared with the SAGE library of the leaf
      constructed on a similar scale. The transcript profiles of pollen reflect
      accurately the characteristics of pollen as a reproductive organ. Functional
      classification of the expressed genes reveals that those involved in cellular
      biogenesis such as polygalacturonase, pectate lyase, and pectin methylesterase
      make up more than 40% of the total transcripts. However, genes involved in energy
      and protein synthesis, which are prevalent in leaves, were expressed at a
      relatively low level. The expression level of the great majority of transcripts
      was unaffected by cold treatment at 0 degrees C for 72 h, whereas pollen tube
      growth and seed production were substantially reduced. Interestingly, many genes
      thought to be responsible for cold acclimation such as COR, lipid transfer
      protein, and beta-amylase, that are highly induced in Arabidopsis leaves, were
      only expressed at their normal level or weakly induced in the pollen. The
      expression patterns of the cold-responsive transcripts identified by SAGE were
      confirmed by microarray analysis. Our results strongly suggest that poor
      accumulation of proteins that play a role in stress tolerance may be why
      Arabidopsis pollen is cold sensitive.

PMID- 12805585
TI  - Expansion of the receptor-like kinase/Pelle gene family and receptor-like
      proteins in Arabidopsis.
AB  - Receptor-like kinases (RLKs) are a family of transmembrane proteins with
      versatile N-terminal extracellular domains and C-terminal intracellular kinases.
      They control a wide range of physiological responses in plants and belong to one
      of the largest gene families in the Arabidopsis genome with more than 600
      members. Interestingly, this gene family constitutes 60% of all kinases in
      Arabidopsis and accounts for nearly all transmembrane kinases in Arabidopsis.
      Analysis of four fungal, six metazoan, and two Plasmodium sp. genomes indicates
      that the family was represented in all but fungal genomes, indicating an ancient
      origin for the family with a more recent expansion only in the plant lineages.
      The RLK/Pelle family can be divided into several subfamilies based on three
      independent criteria: the phylogeny based on kinase domain sequences, the
      extracellular domain identities, and intron locations and phases. A large number
      of receptor-like proteins (RLPs) resembling the extracellular domains of RLKs are
      also found in the Arabidopsis genome. However, not all RLK subfamilies have
      corresponding RLPs. Several RLK/Pelle subfamilies have undergone differential
      expansions. More than 33% of the RLK/Pelle members are found in tandem clusters,
      substantially higher than the genome average. In addition, 470 of the RLK/Pelle
      family members are located within the segmentally duplicated regions in the
      Arabidopsis genome and 268 of them have a close relative in the corresponding
      regions. Therefore, tandem duplications and segmental/whole-genome duplications
      represent two of the major mechanisms for the expansion of the RLK/Pelle family
      in Arabidopsis.

PMID- 12805586
TI  - The SAC domain-containing protein gene family in Arabidopsis.
AB  - The SAC domain was first identified in the yeast (Saccharomyces cerevisiae) Sac1p
      phosphoinositide phosphatase protein and subsequently found in a number of
      proteins from yeast and animals. The SAC domain is approximately 400 amino acids
      in length and is characterized by seven conserved motifs. The SAC domains of
      several proteins have been recently demonstrated to possess phosphoinositide
      phosphatase activities. Sac1p has been shown to regulate the levels of various
      phosphoinositides in the phosphoinositide pool and affect diverse cellular
      functions such as actin cytoskeleton organization, Golgi function, and
      maintenance of vacuole morphology. The Arabidopsis genome contains a total of
      nine genes encoding SAC domain-containing proteins (AtSACs). The SAC domains of
      the AtSACs possess the conserved amino acid motifs that are believed to be
      important for the phosphoinositide phosphatase activities of yeast and animal SAC
      domain proteins. AtSACs can be divided into three subgroups based on their
      sequence similarities, hydropathy profiles, and phylogenetic relationship. Gene
      expression analysis demonstrated that the AtSAC genes exhibited differential
      expression patterns in different organs and, in particular, the AtSAC6 gene was
      predominantly expressed in flowers. Moreover, the expression of the AtSAC6 gene
      was highly induced by salinity. These results provide a foundation for future
      studies on the elucidation of the cellular functions of SAC domain-containing
      proteins in Arabidopsis.

PMID- 12805587
TI  - Microarray analysis of the nitrate response in Arabidopsis roots and shoots
      reveals over 1,000 rapidly responding genes and new linkages to glucose,
      trehalose-6-phosphate, iron, and sulfate metabolism.
AB  - The genomic response to low levels of nitrate was studied in Arabidopsis using
      the Affymetrix ATH1 chip containing more than 22,500 probe sets. Arabidopsis
      plants were grown hydroponically in sterile liquid culture on ammonium as the
      sole source of nitrogen for 10 d, then treated with 250 microm nitrate for 20
      min. The response to nitrate was much stronger in roots (1,176 genes showing
      increased or decreased mRNA levels) than in shoots (183 responding genes). In
      addition to known nitrate-responsive genes (e.g. those encoding nitrate
      transporters, nitrate reductase, nitrite reductase, ferredoxin reductase, and
      enzymes in the pentose phosphate pathway), genes encoding novel metabolic and
      potential regulatory proteins were found. These genes encode enzymes in
      glycolysis (glucose-6-phosphate isomerase and phosphoglycerate mutase), in
      trehalose-6-P metabolism (trehalose-6-P synthase and trehalose-6-P phosphatase),
      in iron transport/metabolism (nicotianamine synthase), and in sulfate
      uptake/reduction. In many cases, only a few select genes out of several in small
      gene families were induced by nitrate. These results show that the effect of
      nitrate on gene expression is substantial (affecting almost 10% of the genes with
      detectable mRNA levels) yet selective and affects many genes involved in carbon
      and nutrient metabolism.

PMID- 12805588
TI  - Identification of glycosylphosphatidylinositol-anchored proteins in Arabidopsis.
      A proteomic and genomic analysis.
AB  - In a recent bioinformatic analysis, we predicted the presence of multiple
      families of cell surface glycosylphosphatidylinositol (GPI)-anchored proteins
      (GAPs) in Arabidopsis (G.H.H. Borner, D.J. Sherrier, T.J. Stevens, I.T. Arkin, P.
      Dupree [2002] Plant Physiol 129: 486-499). A number of publications have since
      demonstrated the importance of predicted GAPs in diverse physiological processes
      including root development, cell wall integrity, and adhesion. However, direct
      experimental evidence for their GPI anchoring is mostly lacking. Here, we present
      the first, to our knowledge, large-scale proteomic identification of plant GAPs.
      Triton X-114 phase partitioning and sensitivity to phosphatidylinositol-specific
      phospholipase C were used to prepare GAP-rich fractions from Arabidopsis callus
      cells. Two-dimensional fluorescence difference gel electrophoresis and one
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      demonstrated the existence of a large number of phospholipase C-sensitive
      Arabidopsis proteins. Using liquid chromatography-tandem mass spectrometry, 30
      GAPs were identified, including six beta-1,3 glucanases, five phytocyanins, four
      fasciclin-like arabinogalactan proteins, four receptor-like proteins, two
      Hedgehog-interacting-like proteins, two putative glycerophosphodiesterases, a
      lipid transfer-like protein, a COBRA-like protein, SKU5, and SKS1. These results
      validate our previous bioinformatic analysis of the Arabidopsis protein database.
      Using the confirmed GAPs from the proteomic analysis to train the search
      algorithm, as well as improved genomic annotation, an updated in silico screen
      yielded 64 new candidates, raising the total to 248 predicted GAPs in
      Arabidopsis.

PMID- 12805589
TI  - Changes in gene expression in Arabidopsis shoots during phosphate starvation and
      the potential for developing smart plants.
AB  - Our aim was to generate and prove the concept of "smart" plants to monitor plant
      phosphorus (P) status in Arabidopsis. Smart plants can be genetically engineered
      by transformation with a construct containing the promoter of a gene up-regulated
      specifically by P starvation in an accessible tissue upstream of a marker gene
      such as beta-glucuronidase (GUS). First, using microarrays, we identified genes
      whose expression changed more than 2.5-fold in shoots of plants growing
      hydroponically when P, but not N or K, was withheld from the nutrient solution.
      The transient changes in gene expression occurring immediately (4 h) after P
      withdrawal were highly variable, and many nonspecific, shock-induced genes were
      up-regulated during this period. However, two common putative cis-regulatory
      elements (a PHO-like element and a TATA box-like element) were present
      significantly more often in the promoters of genes whose expression increased 4 h
      after the withdrawal of P compared with their general occurrence in the promoters
      of all genes represented on the microarray. Surprisingly, the expression of only
      four genes differed between shoots of P-starved and -replete plants 28 h after P
      was withdrawn. This lull in differential gene expression preceded the
      differential expression of a new group of 61 genes 100 h after withdrawing P. A
      literature survey indicated that the expression of many of these "late" genes
      responded specifically to P starvation. Shoots had reduced P after 100 h, but
      growth was unaffected. The expression of SQD1, a gene involved in the synthesis
      of sulfolipids, responded specifically to P starvation and was increased 100 h
      after withdrawing P. Leaves of Arabidopsis bearing a SQD1::GUS construct showed
      increased GUS activity after P withdrawal, which was detectable before P
      starvation limited growth. Hence, smart plants can monitor plant P status.
      Transferring this technology to crops would allow precision management of P
      fertilization, thereby maintaining yields while reducing costs, conserving
      natural resources, and preventing pollution.

PMID- 12805590
TI  - Transcriptome profiling of sulfur-responsive genes in Arabidopsis reveals global
      effects of sulfur nutrition on multiple metabolic pathways.
AB  - Sulfate is a macronutrient required for cell growth and development. Arabidopsis
      has two high-affinity sulfate transporters (SULTR1;1 and SULTR1;2) that represent
      the sulfate uptake activities at the root surface. Sulfur limitation (-S)
      response relevant to the function of SULTR1;2 was elucidated in this study. We
      have isolated a novel T-DNA insertion allele defective in the SULTR1;2 sulfate
      transporter. This mutant, sel1-10, is allelic with the sel1 mutants identified
      previously in a screen for increased tolerance to selenate, a toxic analog of
      sulfate (Shibagaki et al., 2002). The abundance of SULTR1;1 mRNA was
      significantly increased in the sel1-10 mutant; however, this compensatory up
      regulation of SULTR1;1 was not sufficient to restore the growth. The sulfate
      content of the mutant was 10% to 20% of the wild type, suggesting that induction
      of SULTR1;1 is not fully complementing the function of SULTR1;2 and that SULTR1;2
      serves as the major facilitator for the acquisition of sulfate in Arabidopsis
      roots. Transcriptome analysis of approximately 8,000 Arabidopsis genes in the
      sel1-10 mutant suggested that dysfunction of the SULTR1;2 transporter can mimic
      general -S symptoms. Hierarchal clustering of sulfur responsive genes in the wild
      type and mutant indicated that sulfate uptake, reductive sulfur assimilation, and
      turnover of secondary sulfur metabolites are activated under -S. The profiles of 
      S-responsive genes further suggested induction of genes that may alleviate
      oxidative damage and generation of reactive oxygen species caused by shortage of
      glutathione.

PMID- 12805591
TI  - Characterization of the early response of Arabidopsis to Alternaria brassicicola
      infection using expression profiling.
AB  - All tested accessions of Arabidopsis are resistant to the fungal pathogen
      Alternaria brassicicola. Resistance is compromised by pad3 or coi1 mutations,
      suggesting that it requires the Arabidopsis phytoalexin camalexin and jasmonic
      acid (JA)-dependent signaling, respectively. This contrasts with most well
      studied Arabidopsis pathogens, which are controlled by salicylic acid-dependent
      responses and do not benefit from absence of camalexin or JA. Here, mutants with
      defects in camalexin synthesis (pad1, pad2, pad3, and pad5) or in JA signaling
      (pad1, coi1) were found to be more susceptible than wild type. Mutants with
      defects in salicylic acid (pad4 and sid2) or ethylene (ein2) signaling remained
      resistant. Plant responses to A. brassicicola were characterized using expression
      profiling. Plants showed dramatic gene expression changes within 12 h, persisting
      at 24 and 36 h. Wild-type and pad3 plants responded similarly, suggesting that
      pad3 does not have a major effect on signaling. The response of coi1 plants was
      quite different. Of the 645 genes induced by A. brassicicola in wild-type and
      pad3 plants, 265 required COI1 for full expression. It is likely that some of the
      COI1-dependent genes are important for resistance to A. brassicicola. Responses
      to A. brassicicola were compared with responses to Pseudomonas syringae
      infection. Despite the fact that these pathogens are limited by different defense
      responses, approximately 50% of the induced genes were induced in response to
      both pathogens. Among these, requirements for COI1 were consistent after
      infection by either pathogen, suggesting that the regulatory effect of COI1 is
      similar regardless of the initial stimulus.

PMID- 12805592
TI  - Genomic comparison of P-type ATPase ion pumps in Arabidopsis and rice.
AB  - Members of the P-type ATPase ion pump superfamily are found in all three branches
      of life. Forty-six P-type ATPase genes were identified in Arabidopsis, the
      largest number yet identified in any organism. The recent completion of two draft
      sequences of the rice (Oryza sativa) genome allows for comparison of the full
      complement of P-type ATPases in two different plant species. Here, we identify a
      similar number (43) in rice, despite the rice genome being more than three times
      the size of Arabidopsis. The similarly large families suggest that both dicots
      and monocots have evolved with a large preexisting repertoire of P-type ATPases.
      Both Arabidopsis and rice have representative members in all five major
      subfamilies of P-type ATPases: heavy-metal ATPases (P1B), Ca2+-ATPases
      (endoplasmic reticulum-type Ca2+-ATPase and autoinhibited Ca2+-ATPase, P2A and
      P2B), H+-ATPases (autoinhibited H+-ATPase, P3A), putative aminophospholipid
      ATPases (ALA, P4), and a branch with unknown specificity (P5). The close pairing
      of similar isoforms in rice and Arabidopsis suggests potential orthologous
      relationships for all 43 rice P-type ATPases. A phylogenetic comparison of
      protein sequences and intron positions indicates that the common angiosperm
      ancestor had at least 23 P-type ATPases. Although little is known about unique
      and common features of related pumps, clear differences between some members of
      the calcium pumps indicate that evolutionarily conserved clusters may distinguish
      pumps with either different subcellular locations or biochemical functions.

PMID- 12805593
TI  - Enhancer trapping reveals widespread circadian clock transcriptional control in
      Arabidopsis.
AB  - The circadian clock synchronizes the internal biology of an organism with the
      environment and has been shown to be widespread among organisms. Microarray
      experiments have shown that the circadian clock regulates mRNA abundance of about
      10% of the transcriptome in plants, invertebrates, and mammals. In contrast, the
      circadian clock regulates the transcription of the virtually all cyanobacterial
      genes. To determine the extent to which the circadian clock controls
      transcription in Arabidopsis, we used in vivo enhancer trapping. We found that
      36% of our enhancer trap lines display circadian-regulated transcription, which
      is much higher than estimates of circadian regulation based on analysis of steady
      state mRNA abundance. Individual lines identified by enhancer trapping exhibit
      peak transcription rates at circadian phases spanning the complete circadian
      cycle. Flanking genomic sequence was identified for 23 enhancer trap lines to
      identify clock-controlled genes (CCG-ETs). Promoter analysis of CCG-ETs failed to
      predict new circadian clock response elements (CCREs), although previously
      defined CCREs, the CCA1-binding site, and the evening element were identified.
      However, many CCGs lack either the CCA1-binding site or the evening element;
      therefore, the presence of these CCREs is insufficient to confer circadian
      regulation, and it is clear that additional elements play critical roles.

PMID- 12805594
TI  - Comparative analysis of the Arabidopsis pollen transcriptome.
AB  - We present a genome-wide view of the male gametophytic transcriptome in
      Arabidopsis based on microarray analysis. In comparison with the transcriptome of
      the sporophyte throughout development, the pollen transcriptome showed reduced
      complexity and a unique composition. We identified 992 pollen-expressed mRNAs,
      nearly 40% of which were detected specifically in pollen. Analysis of the
      functional composition of the pollen transcriptome revealed the over
      representation of mRNAs encoding proteins involved in cell wall metabolism,
      cytoskeleton, and signaling and under-representation of mRNAs involved in
      transcription and protein synthesis. For several gene families, we observed a
      common pattern of mutually exclusive gene expression between pollen and
      sporophytic tissues for different gene family members. Our results provide a 50
      fold increase in the knowledge of genes expressed in Arabidopsis pollen.
      Moreover, we also detail the extensive overlap (61%) of the pollen transcriptome
      with that of the sporophyte, which provides ample potential to influence
      sporophytic fitness through gametophytic selection.

PMID- 12805595
TI  - The identification of candidate genes for a reverse genetic analysis of
      development and function in the Arabidopsis gynoecium.
AB  - The screening for mutants and their subsequent molecular analysis has permitted
      the identification of a number of genes of Arabidopsis involved in the
      development and functions of the gynoecium. However, these processes remain far
      from completely understood. It is clear that in many cases, genetic redundancy
      and other factors can limit the efficiency of classical mutant screening. We have
      taken the alternative approach of a reverse genetic analysis of gene function in
      the Arabidopsis gynoecium. A high-throughput fluorescent differential display
      screen performed between two Arabidopsis floral homeotic mutants has permitted
      the identification of a number of genes that are specifically or preferentially
      expressed in the gynoecium. Here, we present the results of this screen and a
      detailed characterization of the expression profiles of the genes identified. Our
      expression analysis makes novel use of several Arabidopsis floral homeotic
      mutants to provide floral organ-specific gene expression profiles. The results of
      these studies permit the efficient targeting of effort into a functional analysis
      of gynoecium-expressed genes.

PMID- 12805597
TI  - Arabidopsis genes involved in acyl lipid metabolism. A 2003 census of the
      candidates, a study of the distribution of expressed sequence tags in organs, and
      a web-based database.
AB  - The genome of Arabidopsis has been searched for sequences of genes involved in
      acyl lipid metabolism. Over 600 encoded proteins have been identified, cataloged,
      and classified according to predicted function, subcellular location, and
      alternative splicing. At least one-third of these proteins were previously
      annotated as "unknown function" or with functions unrelated to acyl lipid
      metabolism; therefore, this study has improved the annotation of over 200 genes.
      In particular, annotation of the lipolytic enzyme group (at least 110 members
      total) has been improved by the critical examination of the biochemical
      literature and the sequences of the numerous proteins annotated as "lipases." In
      addition, expressed sequence tag (EST) data have been surveyed, and more than
      3,700 ESTs associated with the genes were cataloged. Statistical analysis of the
      number of ESTs associated with specific cDNA libraries has allowed calculation of
      probabilities of differential expression between different organs. More than 130
      genes have been identified with a statistical probability > 0.95 of preferential
      expression in seed, leaf, root, or flower. All the data are available as a Web
      based database, the Arabidopsis Lipid Gene database
      (http://www.plantbiology.msu.edu/lipids/genesurvey/index.htm). The combination of
      the data of the Lipid Gene Catalog and the EST analysis can be used to gain
      insights into differential expression of gene family members and sets of pathway
      specific genes, which in turn will guide studies to understand specific functions
      of individual genes.

PMID- 12805596
TI  - The Arabidopsis CDPK-SnRK superfamily of protein kinases.
AB  - The CDPK-SnRK superfamily consists of seven types of serine-threonine protein
      kinases: calcium-dependent protein kinase (CDPKs), CDPK-related kinases (CRKs),
      phosphoenolpyruvate carboxylase kinases (PPCKs), PEP carboxylase kinase-related
      kinases (PEPRKs), calmodulin-dependent protein kinases (CaMKs), calcium and
      calmodulin-dependent protein kinases (CCaMKs), and SnRKs. Within this
      superfamily, individual isoforms and subfamilies contain distinct regulatory
      domains, subcellular targeting information, and substrate specificities. Our
      analysis of the Arabidopsis genome identified 34 CDPKs, eight CRKs, two PPCKs,
      two PEPRKs, and 38 SnRKs. No definitive examples were found for a CCaMK similar
      to those previously identified in lily (Lilium longiflorum) and tobacco
      (Nicotiana tabacum) or for a CaMK similar to those in animals or yeast. CDPKs are
      present in plants and a specific subgroup of protists, but CRKs, PPCKs, PEPRKs,
      and two of the SnRK subgroups have been found only in plants. CDPKs and at least
      one SnRK have been implicated in decoding calcium signals in Arabidopsis.
      Analysis of intron placements supports the hypothesis that CDPKs, CRKs, PPCKs and
      PEPRKs have a common evolutionary origin; however there are no conserved intron
      positions between these kinases and the SnRK subgroup. CDPKs and SnRKs are found
      on all five Arabidopsis chromosomes. The presence of closely related kinases in
      regions of the genome known to have arisen by genome duplication indicates that
      these kinases probably arose by divergence from common ancestors. The PlantsP
      database provides a resource of continuously updated information on protein
      kinases from Arabidopsis and other plants.

PMID- 12805598
TI  - Secretion trap tagging of secreted and membrane-spanning proteins using
      Arabidopsis gene traps.
AB  - Secreted and membrane-spanning proteins play fundamental roles in plant
      development but pose challenges for genetic identification and characterization.
      We describe a "secretion trap" screen for gene trap insertions in genes encoding
      proteins routed through the secretory pathway. The gene trap transposon encodes a
      beta-glucuronidase reporter enzyme that is inhibited by N-linked glycosylation
      specific to the secretory pathway. Treatment of seedlings with tunicamycin
      inhibits glycosylation, resulting in increased activity of secreted beta
      glucuronidase fusions that result from gene trap integration downstream of exons
      encoding signal peptides. In the 2,059 gene trap lines that we screened, 32
      secretion trap expression patterns were identified in a wide variety of tissues
      including embryos, meristems, and the developing vasculature. Genes disrupted by
      the secretion traps encode putative extracellular signaling proteins, membrane
      transport proteins, and novel secreted proteins of unknown function missed by
      conventional mutagenesis and gene prediction. Secretion traps provide a unique
      reagent for gene expression studies and can guide the genetic combination of loss
      of function alleles in related genes.

PMID- 12805599
TI  - MicroRNAs: at the root of plant development?

PMID- 12805600
TI  - The impact of genomics on the study of natural variation in Arabidopsis.

PMID- 12805601
TI  - A cyclic nucleotide-gated ion channel, CNGC2, is crucial for plant development
      and adaptation to calcium stress.

PMID- 12805602
TI  - The circadian clock. A plant's best friend in a spinning world.

PMID- 12805603
TI  - AtSig5 is an essential nucleus-encoded Arabidopsis sigma-like factor.
AB  - Transcription of chloroplast genes is subject to control by nucleus-encoded
      proteins. The chloroplast-encoded RNA polymerase (PEP) is a eubacterial-type RNA
      polymerase that is presumed to assemble with nucleus-encoded sigma-factors
      mediating promoter recognition. Recently, families of sigma-factor genes have
      been identified in several plants including Arabidopsis. One of these genes,
      Arabidopsis SIG5, encodes a sigma-factor, AtSig5, which is phylogenetically
      distinct from the other family members. To investigate the role of this plant
      sigma-factor, two different insertional alleles of the SIG5 gene were identified
      and characterized. Heterozygous mutant plants showed no visible leaf phenotype,
      but exhibited siliques containing aborted embryos and unfertilized ovules. Our
      inability to recover plants homozygous for a SIG5 gene disruption indicates that
      SIG5 is an essential gene. SIG5 transcripts accumulate in flower tissues,
      consistent with a role for AtSig5 protein in reproduction. Therefore, SIG5
      encodes an essential member of the Arabidopsis sigma-factor family that plays a
      role in plant reproduction in addition to its previously proposed role in leaf
      chloroplast gene expression.

PMID- 12805604
TI  - Expression of antisense acyl carrier protein-4 reduces lipid content in
      Arabidopsis leaf tissue.
AB  - Arabidopsis plants were transformed with acyl carrier protein (ACP)-4 in
      antisense conformation driven by the cauliflower mosaic virus 35S promoter. It
      was hypothesized that reduction of ACP4 in leaf tissue would result in a
      reduction in lipid biosynthesis and, in addition, affect fatty acid composition
      and leaf physiology. Several transgenic lines have been generated with reduced
      ACP4 protein in leaf tissue. Dramatic reductions in ACP4 resulted in a reduction
      of leaf lipid content (22%-60%) based on fresh leaf weight and a bleached
      appearance and reduced photosynthetic efficiency. In addition, a decrease in 16:3
      as a percentage of the total fatty acid composition was noted. There were no
      changes in leaf lipid class distribution; however, there was a decrease in the
      relative amount of 16:3 in monogalactosyldiacylglycerol. These results suggest
      that ACP4 plays a major role in the biosynthesis of fatty acids for chloroplast
      membrane development. Alterations in the ACP isoform profile of Arabidopsis leaf
      also appear to alter the flow of fatty acids between the prokaryotic and
      eukaryotic pathways for assembly of galactolipids. However, it has not yet been
      determined if the changes in fatty acid composition are due to changes in the
      profile of ACP isoforms, or if they are actually a reaction to a reduction in
      fatty acid precursors.

PMID- 12805605
TI  - Arabidopsis hot mutants define multiple functions required for acclimation to
      high temperatures.
AB  - Plants acquire thermotolerance to lethal high temperatures if first exposed to
      moderately high temperature or if temperature is increased gradually to an
      otherwise lethal temperature. We have taken a genetic approach to dissecting
      acquired thermotolerance by characterizing loss-of-function thermotolerance
      mutants in Arabidopsis. In previous work, we identified single recessive alleles
      of four loci required for thermotolerance of hypocotyl elongation, hot1-1, hot2
      1, hot3-1, and hot4-1. Completed screening of M2 progeny from approximately 2500
      M1 plants has now identified new alleles of three of these original loci, along
      with three new loci. The low mutant frequency suggests that a relatively small
      number of genes make a major contribution to this phenotype or that other
      thermotolerance genes encode essential or redundant functions. Further analysis
      of the original four loci was performed to define the nature of their
      thermotolerance defects. Although the HOT1 locus was shown previously to encode a
      major heat shock protein (Hsp), Hsp101, chromosomal map positions indicate that
      HOT2, 3, and 4 do not correspond to major Hsp or heat shock transcription factor
      genes. Measurement of thermotolerance at different growth stages reveals that the
      mutants have growth stage-specific heat sensitivity. Analysis of Hsp accumulation
      shows that hot2 and hot4 produce normal levels of Hsps, whereas hot3 shows
      reduced accumulation. Thermotolerance of luciferase activity and of ion leakage
      also varies in the mutants. These data provide the first direct genetic evidence,
      to our knowledge, that distinct functions, independent of Hsp synthesis, are
      required for thermotolerance, including protection of membrane integrity and
      recovery of protein activity/synthesis.

PMID- 12805606
TI  - Analysis of xyloglucan fucosylation in Arabidopsis.
AB  - Xyloglucan (XyG) is a load-bearing primary wall component in dicotyledonous and
      non-graminaceous monocotyledonous plants. XyG fucosyltransferase (FUTase),
      encoded by the Arabidopsis gene AtFUT1, directs addition of fucose (Fuc) residues
      to terminal galactose residues on XyG side chains. Reverse transcription
      polymerase chain reaction and analysis of promoter-beta-glucuronidase transgenic
      plants indicated highest expression of AtFUT1 in the upper portion of elongating
      inflorescence stems of Arabidopsis. XyG FUTase activity was highest in Golgi
      vesicles prepared from growing Arabidopsis tissues and low in those isolated from
      mature tissues. There was no discernible correlation between the Fuc contents of
      XyG oligosaccharides derived from different Arabidopsis organs and the level of
      AtFUT1 expression in the organs. Thus, organ-specific variations in AtFUT1
      expression and enzyme activity probably reflect differential rates of cell wall
      biosynthesis, rather than differences in levels of XyG fucosylation. The effects
      of manipulating AtFUT1 expression were examined using an Arabidopsis mutant
      (atfut1) containing a T-DNA insertion in the AtFUT1 locus and transgenic plants
      with strong constitutive expression of AtFUT1. No Fuc was detected in XyG derived
      from leaves or roots of atfut1. Plants overexpressing AtFUT1 had higher XyG
      FUTase activity than wild-type plants, but the XyG oligosaccharides derived from
      the transgenic and wild-type plants contained comparable amounts of Fuc,
      indicating that suitable acceptor substrates are limiting. Galactosyl residues
      had slightly higher levels of O-acetylation in XyG from plants that overexpressed
      AtFUT1 than in XyG from wild-type plants. O-Acetylation of galactose residues was
      considerably reduced in Fuc-deficient mutants (atfut1, mur1, and mur2) that
      synthesize XyG containing little or no Fuc. These results suggest that
      fucosylated XyG is a suitable substrate for at least one O-acetyltransferase in
      Arabidopsis.

PMID- 12805607
TI  - Seed-specific overexpression of an endogenous Arabidopsis phytoene synthase gene
      results in delayed germination and increased levels of carotenoids, chlorophyll,
      and abscisic acid.
AB  - Phytoene synthase catalyzes the dimerization of two molecules of geranylgeranyl
      pyrophosphate to phytoene and has been shown to be rate limiting for the
      synthesis of carotenoids. To elucidate if the capacity to produce phytoene is
      limiting also in the seed of Arabidopsis (Wassilewskija), a gene coding for an
      endogenous phytoene synthase was cloned and coupled to a seed-specific promoter,
      and the effects of the overexpression were examined. The resulting transgenic
      plants produced darker seeds, and extracts from the seed of five overexpressing
      plants had a 43-fold average increase of beta-carotene and a total average amount
      of beta-carotene of approximately 260 microg g-1 fresh weight. Lutein,
      violaxanthin, and chlorophyll were significantly increased, whereas the levels of
      zeaxanthin only increased by a factor 1.1. In addition, substantial levels of
      lycopene and alpha-carotene were produced in the seeds, whereas only trace
      amounts were found in the control plants. Seeds from the transgenic plants
      exhibited delayed germination, and the degree of delay was positively correlated
      with the increased levels of carotenoids. The abscisic acid levels followed the
      increase of the carotenoids, and plants having the highest carotenoid levels also
      had the highest abscisic acid content. Addition of gibberellic acid to the growth
      medium only partly restored germination of the transgenic seeds.

PMID- 12805608
TI  - Expression of a mutant form of cellulose synthase AtCesA7 causes dominant
      negative effect on cellulose biosynthesis.
AB  - Cellulose synthase catalytic subunits (CesAs) have been implicated in catalyzing
      the biosynthesis of cellulose, the major component of plant cell walls.
      Interactions between CesA subunits are thought to be required for normal
      cellulose synthesis, which suggests that incorporation of defective CesA subunits
      into cellulose synthase complex could potentially cause a dominant effect on
      cellulose synthesis. However, all CesA mutants so far reported have been shown to
      be recessive in terms of cellulose synthesis. In the course of studying the
      molecular mechanisms regulating secondary wall formation in fibers, we have found
      that a mutant allele of AtCesA7 gene in the fra5 (fragile fiber 5) mutant causes
      a semidominant phenotype in the reduction of fiber cell wall thickness and
      cellulose content. The fra5 missense mutation occurred in a conserved amino acid
      located in the second cytoplasmic domain of AtCesA7. Overexpression of the fra5
      mutant cDNA in wild-type plants not only reduced secondary wall thickness and
      cellulose content but also decreased primary wall thickness and cell elongation.
      In contrast, overexpression of the fra6 mutant form of AtCesA8 did not cause any
      reduction in cell wall thickness and cellulose content. These results suggest
      that the fra5 mutant protein may interfere with the function of endogenous wild
      type CesA proteins, thus resulting in a dominant negative effect on cellulose
      biosynthesis.

PMID- 12805609
TI  - Dual regulation of the Arabidopsis high-affinity root iron uptake system by local
      and long-distance signals.
AB  - Regulation of the root high-affinity iron uptake system by whole-plant signals
      was investigated at the molecular level in Arabidopsis, through monitoring FRO2
      and IRT1 gene expression. These two genes encode the root ferric-chelate
      reductase and the high-affinity iron transporter, respectively, involved in the
      iron deficiency-induced uptake system. Recovery from iron-deficient conditions
      and modulation of apoplastic iron pools indicate that iron itself plays a major
      role in the regulation of root iron deficiency responses at the mRNA and protein
      levels. Split-root experiments show that the expression of IRT1 and FRO2 is
      controlled both by a local induction from the root iron pool and through a
      systemic pathway involving a shoot-borne signal, both signals being integrated to
      tightly control production of the root iron uptake proteins. We also show that
      IRT1 and FRO2 are expressed during the day and down-regulated at night and that
      this additional control is overruled by iron starvation, indicating that the
      nutritional status prevails on the diurnal regulation. Our work suggests, for the
      first time to our knowledge, that like in grasses, the root iron acquisition in
      strategy I plants may also be under diurnal regulation. On the basis of the new
      molecular insights provided in this study and given the strict coregulation of
      IRT1 and FRO2 observed, we present a model of local and long-distance regulation
      of the root iron uptake system in Arabidopsis.

PMID- 12805610
TI  - Hydrotropism interacts with gravitropism by degrading amyloplasts in seedling
      roots of Arabidopsis and radish.
AB  - In response to a moisture gradient, roots exhibit hydrotropism to control the
      orientation of their growth. To exhibit hydrotropism, however, they must overcome
      the gravitropism that is dominant on Earth. We found that moisture gradient or
      water stress caused immediate degradation of the starch anchors, amyloplasts, in
      root columella cells of Arabidopsis and radish (Raphanus sativus). Namely,
      development of hydrotropic response was accompanied by a simultaneous reduction
      in starch content in columella cells. Rapid degradation of amyloplasts in
      columella cells also occurred in the water-stressed roots with sorbitol or
      mannitol. Both hydrotropically stimulated and water-stressed roots showed a
      reduced responsiveness to gravity. Roots of a starchless mutant, pgm1-1, showed
      an enhanced hydrotropism compared with that of the wild type. These results
      suggest that the reduced responsiveness to gravity is, at least in part,
      attributable to the degradation of amyloplasts in columella cells. Thus, the
      reduction in gravitropism allows the roots to exhibit hydrotropism.

PMID- 12805611
TI  - Light stress-induced one-helix protein of the chlorophyll a/b-binding family
      associated with photosystem I.
AB  - The superfamily of light-harvesting chlorophyll a/b-binding (Lhc) proteins in
      higher plants and green algae is composed of more than 20 different antenna
      proteins associated either with photosystem I (PSI) or photosystem II (PSII).
      Several distant relatives of this family with conserved chlorophyll-binding
      residues and proposed photoprotective functions are induced transiently under
      various stress conditions. Whereas "classical" Lhc proteins contain three
      transmembrane alpha-helices, their distant relatives span the membrane with
      between one and four transmembrane segments. Here, we report the identification
      and isolation of a novel member of the Lhc family from Arabidopsis with one
      predicted transmembrane alpha-helix closely related to helix I of Lhc protein
      from PSI (Lhca4) that we named Ohp2 (for a second one-helix protein of Lhc family
      described from higher plants). We showed that the Ohp2 gene expression is
      triggered by light stress and that the Ohp2 transcript and protein accumulated in
      a light intensity-dependent manner. Other stress conditions did not up-regulate
      the expression of the Ohp2 gene. Localization studies revealed that Ohp2 is
      associated with PSI under low- or high-light conditions. Because all stress
      induced Lhc relatives reported so far were found in PSII, we propose that the
      accumulation of Ohp2 might represent a novel photoprotective strategy induced
      within PSI in response to light stress.

PMID- 12805612
TI  - The monosaccharide transporter gene, AtSTP4, and the cell-wall invertase,
      Atbetafruct1, are induced in Arabidopsis during infection with the fungal
      biotroph Erysiphe cichoracearum.
AB  - Powdery mildew fungi are biotrophic pathogens that form a complex interface, the
      haustorium, between the host plant and the parasite. The pathogen acts as an
      additional sink, competing with host sinks, resulting in considerable
      modification of photoassimilate production and partitioning within the host
      tissue. Here, we examine the factors that may contribute to these changes. We
      show for the first time in one biotrophic interaction (Arabidopsis/Erysiphe
      cichoracearum) all of the following responses: Glc uptake in host tissues is
      enhanced after fungal infection; this coincides with the induction of expression
      of the monosaccharide transporter gene, Arabidopsis sugar transport protein 4
      (AtSTP4), in infected leaves; invertase activity and transcript levels for a cell
      wall invertase, Atbetafruct1, increase substantially in Arabidopsis during attack
      by this pathogen. Before infection, Arabidopsis plants transformed with an AtSTP4
      promoter-beta-glucuronidase construct show expression mainly in sink tissues such
      as roots; after infection, AtSTP4 expression is induced in the mature leaves and
      increases over the 6-d time period. Sections of infected leaves stained for beta
      glucuronidase show that AtSTP4 expression is not confined to infected epidermal
      cells but is also evident in a wider range of cells, including those of the
      vascular tissue. The results are discussed in relation to the possible
      coordinated expression of hexose transporters and cell wall invertase in the host
      response to powdery mildew infection.

PMID- 12805613
TI  - Overexpression of AtCPS and AtKS in Arabidopsis confers increased ent-kaurene
      production but no increase in bioactive gibberellins.
AB  - The plant growth hormone gibberellin (GA) is important for many aspects of plant
      growth and development. Although most genes encoding enzymes at each step of the
      GA biosynthetic pathway have been cloned, their regulation is less well
      understood. To assess how up-regulation of early steps affects the biosynthetic
      pathway overall, we have examined transgenic Arabidopsis plants that overexpress
      either AtCPS or AtKS or both. These genes encode the enzymes ent-copalyl
      diphosphate synthase (CPS) and ent-kaurene synthase, which catalyze the first two
      committed steps in GA biosynthesis. We find that both CPS and CPS/ent-kaurene
      synthase overexpressors have greatly increased levels of the early intermediates
      ent-kaurene and ent-kaurenoic acid, but a lesser increase of later metabolites.
      These overexpression lines do not exhibit any GA overdose morphology and have
      wild-type levels of bioactive GAs. Our data show that CPS is limiting for ent
      kaurene production and suggest that conversion of ent-kaurenoic acid to GA12 by
      ent-kaurenoic acid oxidase may be an important rate-limiting step for production
      of bioactive GA. These results demonstrate the ability of plants to maintain GA
      homeostasis despite large changes in accumulation of early intermediates in the
      biosynthetic pathway.

PMID- 12805614
TI  - The pattern of systemic acquired resistance induction within the Arabidopsis
      rosette in relation to the pattern of translocation.
AB  - Local leaf infections by a necrogenic pathogen can lead to systemic acquired
      resistance (SAR) in untreated leaves. We reasoned that, whatever the nature of
      the long-distance signal, if it is transported in the phloem, the pattern of SAR
      induced within the plant by treatment of a single leaf should match the pattern
      of translocation out of that leaf. The source-sink relationships (orthostichies)
      in the Arabidopsis rosette were established with [14C]Suc or phloem-mobile 3
      aminotriazole at herbicidal concentrations. SAR was activated by infiltrating a
      single Columbia leaf with Pseudomonas syringae pv maculicola DC3000/avrRPM1,
      which causes a hypersensitive response. The pattern of SAR in the rosette was
      monitored by assessing the growth of wild-type DC3000 and by measuring the SAR
      markers salicylic acid and PR1 transcripts. Although the orthostichy of a single
      leaf was clearly limited to a row of vertically aligned leaves, SAR and SAR
      markers were also found outside the orthostichy. This indicates that, whatever
      the nature of the long-distance signal from the treated leaf to the upper
      responding leaves, its transport is either not limited exclusively to the phloem
      or the minor proportion of translocate that is not confined to the orthostichy
      contains enough of the SAR systemic signal to set in motion events leading to the
      establishment of the SAR state in the upper leaves.

PMID- 12805615
TI  - Expression pattern of two paralogs encoding cinnamyl alcohol dehydrogenases in
      Arabidopsis. Isolation and characterization of the corresponding mutants.
AB  - Studying Arabidopsis mutants of the phenylpropanoid pathway has unraveled several
      biosynthetic steps of monolignol synthesis. Most of the genes leading to
      monolignol synthesis have been characterized recently in this herbaceous plant,
      except those encoding cinnamyl alcohol dehydrogenase (CAD). We have used the
      complete sequencing of the Arabidopsis genome to highlight a new view of the
      complete CAD gene family. Among nine AtCAD genes, we have identified the two
      distinct paralogs AtCAD-C and AtCAD-D, which share 75% identity and are likely to
      be involved in lignin biosynthesis in other plants. Northern, semiquantitative
      restriction fragment-length polymorphism-reverse transcriptase-polymerase chain
      reaction and western analysis revealed that AtCAD-C and AtCAD-D mRNA and protein
      ratios were organ dependent. Promoter activities of both genes are high in fibers
      and in xylem bundles. However, AtCAD-C displayed a larger range of sites of
      expression than AtCAD-D. Arabidopsis null mutants (Atcad-D and Atcad-C)
      corresponding to both genes were isolated. CAD activities were drastically
      reduced in both mutants, with a higher impact on sinapyl alcohol dehydrogenase
      activity (6% and 38% of residual sinapyl alcohol dehydrogenase activities for
      Atcad-D and Atcad-C, respectively). Only Atcad-D showed a slight reduction in
      Klason lignin content and displayed modifications of lignin structure with a
      significant reduced proportion of conventional S lignin units in both stems and
      roots, together with the incorporation of sinapaldehyde structures ether linked
      at Cbeta. These results argue for a substantial role of AtCAD-D in lignification,
      and more specifically in the biosynthesis of sinapyl alcohol, the precursor of S
      lignin units.

PMID- 12805616
TI  - AtCHIP, a U-box-containing E3 ubiquitin ligase, plays a critical role in
      temperature stress tolerance in Arabidopsis.
AB  - The Arabidopsis gene AtCHIP encodes a protein with three tetratricopeptide
      repeats and a U-box domain, which is structurally similar to the animal CHIP
      proteins, a new class of E3 ubiquitin ligases. Like animal CHIP proteins, AtCHIP
      has E3 ubiquitin ligase activity in vitro. AtCHIP is a single-copy gene, and its
      transcript is up-regulated by several stress conditions such as low and high
      temperatures. However, increased AtCHIP expression alone was not correlated with
      increased stress tolerance; in fact, overexpression of AtCHIP in Arabidopsis
      rendered plants more sensitive to both low- and high-temperature treatments.
      Higher electrolyte leakage was observed in leaves of AtCHIP overexpression plants
      after chilling temperature treatment, suggesting that membrane function is likely
      impaired in these plants under such a condition. These results indicate that
      AtCHIP plays an important role in plant cellular metabolism under temperature
      stress conditions.

PMID- 12805617
TI  - Peroxisomal ascorbate peroxidase resides within a subdomain of rough endoplasmic
      reticulum in wild-type Arabidopsis cells.
AB  - Previously we reported (R.T. Mullen, C.S. Lisenbee, J.A. Miernyk, R.N. Trelease
      [1999] Plant Cell 11: 2167-2185) that overexpressed ascorbate peroxidase (APX), a
      peroxisomal membrane protein, sorted indirectly to Bright Yellow-2 cell
      peroxisomes via a subdomain of the endoplasmic reticulum (ER; peroxisomal
      endoplasmic reticulum [pER]). More recently, a pER-like compartment also was
      identified in pumpkin (Cucurbita pepo) and transformed Arabidopsis cells (K.
      Nito, K. Yamaguchi, M. Kondo, M. Hayashi, M. Nishimura [2001] Plant Cell Physiol
      42: 20-27). Here, we characterize more extensively the localization of endogenous
      Arabidopsis peroxisomal APX (AtAPX) in cultured wild-type Arabidopsis cells
      (Arabidopsis var. Landsberg erecta). AtAPX was detected in peroxisomes, but not
      in an ER subcompartment, using immunofluorescence microscopy. However, AtAPX was
      detected readily with immunoblots in both peroxisomal and ER fractions recovered
      from sucrose (Suc) density gradients. Most AtAPX in microsomes (200,000g, 1 h
      pellet) applied to gradients exhibited a Mg2+-induced shift from a distribution
      throughout gradients (approximately 18%-40% [w/w] Suc) to > or =42% (w/w) Suc
      regions of gradients, including pellets, indicative of localization in rough ER
      vesicles. Immunogold electron microscopy of the latter fractions verified these
      findings. Further analyses of peroxisomal and rough ER vesicle fractions revealed
      that AtAPX in both fractions was similarly associated with and located mostly on
      the cytosolic face of the membranes. Thus, at the steady state, endogenous
      peroxisomal AtAPX resides at different levels in rough ER and peroxisomes.
      Collectively, these findings show that rather than being a transiently induced
      sorting compartment formed in response to overexpressed peroxisomal APX, portions
      of rough ER (pER) in wild-type cells serve as a constitutive sorting compartment
      likely involved in posttranslational routing of constitutively synthesized
      peroxisomal APX.

PMID- 12805618
TI  - The GMD1 and GMD2 genes of Arabidopsis encode isoforms of GDP-D-mannose 4,6
      dehydratase with cell type-specific expression patterns.
AB  - l-Fucose (l-Fuc) is a monosaccharide constituent of plant cell wall
      polysaccharides and glycoproteins. The committing step in the de novo synthesis
      of l-Fuc is catalyzed by GDP-d-mannose 4,6-dehydratase, which, in Arabidopsis, is
      encoded by the GMD1 and GMD2 (MUR1) genes. To determine the functional
      significance of this genetic redundancy, the expression patterns of both genes
      were investigated via promoter-beta-glucuronidase fusions and immunolocalization
      of a Fuc-containing epitope. GMD2 is expressed in most cell types of the root,
      with the notable exception of the root tip where strong expression of GMD1 is
      observed. Within shoot organs, GMD1::GUS expression is confined to stipules and
      pollen grains leading to fucosylation of the walls of these cell types in the
      mur1 mutant. These results suggest that GMD2 represents the major housekeeping
      gene for the de novo synthesis of GDP-l-Fuc, whereas GMD1 expression is limited
      to a number of specialized cell types. We conclude that the synthesis of GDP-l
      Fuc is controlled in a cell-autonomous manner by differential expression of two
      isoforms of the same enzyme.

PMID- 12805619
TI  - Gene expression phenotypes of Arabidopsis associated with sensitivity to low
      temperatures.
AB  - Chilling is a common abiotic stress that leads to economic losses in agriculture.
      By comparing the transcriptome of Arabidopsis under normal (22 degrees C) and
      chilling (13 degrees C) conditions, we have surveyed the molecular responses of a
      chilling-resistant plant to acclimate to a moderate reduction in temperature. The
      mRNA accumulation of approximately 20% of the approximately 8,000 genes analyzed
      was affected by chilling. In particular, a highly significant number of genes
      involved in protein biosynthesis displayed an increase in transcript abundance.
      We have analyzed the molecular phenotypes of 12 chilling-sensitive mutants
      exposed to 13 degrees C before any visible phenotype could be detected. The
      number and pattern of expression of chilling-responsive genes in the mutants were
      consistent with their final degree of chilling injury. The mRNA accumulation
      profiles for the chilling-lethal mutants chs1, chs2, and chs3 were highly similar
      and included extensive chilling-induced and mutant-specific alterations in gene
      expression. The expression pattern of the mutants upon chilling suggests that the
      normal function of the mutated loci prevents a damaging widespread effect of
      chilling on transcriptional regulation. In addition, we have identified 634
      chilling-responsive genes with aberrant expression in all of the chilling-lethal
      mutants. This reference gene list, including genes related to lipid metabolism,
      chloroplast function, carbohydrate metabolism and free radical detoxification,
      represents a potential source for genes with a critical role in plant acclimation
      to suboptimal temperatures. The comparison of transcriptome profiles after
      transfer of Arabidopsis plants from 22 degrees C to 13 degrees C versus transfer
      to 4 degrees C suggests that quantitative and temporal differences exist between
      these molecular responses.

PMID- 12805620
TI  - Comparative analysis of SET domain proteins in maize and Arabidopsis reveals
      multiple duplications preceding the divergence of monocots and dicots.
AB  - Histone proteins play a central role in chromatin packaging, and modification of
      histones is associated with chromatin accessibility. SET domain [Su(var)3-9,
      Enhancer-of-zeste, Trithorax] proteins are one class of proteins that have been
      implicated in regulating gene expression through histone methylation. The
      relationships of 22 SET domain proteins from maize (Zea mays) and 32 SET domain
      proteins from Arabidopsis were evaluated by phylogenetic analysis and domain
      organization. Our analysis reveals five classes of SET domain proteins in plants
      that can be further divided into 19 orthology groups. In some cases, such as the
      Enhancer of zeste-like and trithorax-like proteins, plants and animals contain
      homologous proteins with a similar organization of domains outside of the SET
      domain. However, a majority of plant SET domain proteins do not have an animal
      homolog with similar domain organization, suggesting that plants have unique
      mechanisms to establish and maintain chromatin states. Although the domains
      present in plant and animal SET domain proteins often differ, the domains found
      in the plant proteins have been generally implicated in protein-protein
      interactions, indicating that most SET domain proteins operate in complexes.
      Combined analysis of the maize and Arabidopsis SET domain proteins reveals that
      duplication of SET domain proteins in plants is extensive and has occurred via
      multiple mechanisms that preceded the divergence of monocots and dicots.

PMID- 12805621
TI  - Overexpression of the ASN1 gene enhances nitrogen status in seeds of Arabidopsis.
AB  - In wild-type Arabidopsis, levels of ASN1 mRNA and asparagine (Asn) are tightly
      regulated by environmental factors and metabolites. Because Asn serves as an
      important nitrogen storage and transport compound used to allocate nitrogen
      resources between source and sink organs, we tested whether overexpression of the
      major expressed gene for Asn synthetase, ASN1, would lead to changes in nitrogen
      status in the ultimate storage organ for metabolites-seeds. Transgenic
      Arabidopsis constitutively overexpressing ASN1 under the cauliflower mosaic virus
      35S promoter were constructed (35S-ASN1). In seeds of the 35S-ASN1 lines, three
      observations support the notion that the nitrogen status was enhanced: (a)
      elevations of soluble seed protein contents, (b) elevations of total protein
      contents from acid-hydrolyzed seeds, and (c) higher tolerance of young seedlings
      when grown on nitrogen-limiting media. Besides quantitative differences, changes
      in the relative composition of the seed amino acid were also observed. The change
      in seed nitrogen status was accompanied by an increase of total free amino acids
      (mainly Asn) allocated to flowers and developing siliques. In 35S-ASN1 lines,
      sink tissues such as flowers and developing siliques exhibit a higher level of
      free Asn than source tissues such as leaves and stems, despite significantly
      higher levels of ASN1 mRNA observed in the source tissues. This was at least
      partially due to an enhanced transport of Asn from source to sink via the phloem,
      as demonstrated by the increased levels of Asn in phloem exudates of the 35S-ASN1
      plants.

PMID- 12805622
TI  - Identification and characterization of aluminum tolerance loci in Arabidopsis
      (Landsberg erecta x Columbia) by quantitative trait locus mapping. A
      physiologically simple but genetically complex trait.
AB  - Aluminum (Al) toxicity, which is caused by the solubilization of Al3+ in acid
      soils resulting in inhibition of root growth and nutrient/water acquisition, is a
      serious limitation to crop production, because up to one-half of the world's
      potentially arable land is acidic. To date, however, no Al tolerance genes have
      yet been cloned. The physiological mechanisms of tolerance are somewhat better
      understood; the major documented mechanism involves the Al-activated release of
      Al-binding organic acids from the root tip, preventing uptake into the primary
      site of toxicity. In this study, a quantitative trait loci analysis of Al
      tolerance in Arabidopsis was conducted, which also correlated Al tolerance
      quantitative trait locus (QTL) with physiological mechanisms of tolerance. The
      analysis identified two major loci, which explain approximately 40% of the
      variance in Al tolerance observed among recombinant inbred lines derived from
      Landsberg erecta (sensitive) and Columbia (tolerant). We characterized the
      mechanism by which tolerance is achieved, and we found that the two QTL
      cosegregate with an Al-activated release of malate from Arabidopsis roots.
      Although only two of the QTL have been identified, malate release explains nearly
      all (95%) of the variation in Al tolerance in this population. Al tolerance in
      Landsberg erecta x Columbia is more complex genetically than physiologically, in
      that a number of genes underlie a single physiological mechanism involving root
      malate release. These findings have set the stage for the subsequent cloning of
      the genes responsible for the Al tolerance QTL, and a genomics-based cloning
      strategy and initial progress on this are also discussed.

PMID- 12805623
TI  - Identification and expression analysis of a gene encoding a bacterial-type
      phosphoenolpyruvate carboxylase from Arabidopsis and rice.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is distributed in plants and bacteria but
      is not found in fungi and animal cells. Important motifs for enzyme activity and
      structure are conserved in plant and bacterial PEPCs, with the exception of a
      phosphorylation domain present at the N terminus of all plant PEPCs reported so
      far, which is absent in the bacterial enzymes. Here, we describe a gene from
      Arabidopsis, stated as Atppc4, encoding a PEPC, which shows more similarity to
      Escherichia coli than to plant PEPCs. Interestingly, this enzyme lacks the
      phosphorylation domain, hence indicating that it is a bacterial-type PEPC. Three
      additional PEPC genes are present in Arabidopsis, stated as Atppc1, Atppc2, and
      Atppc3, encoding typical plant-type enzymes. As most plant PEPC genes, Atppc1,
      Atppc2, and Atppc3 are formed by 10 exons interrupted by nine introns. In
      contrast, Atppc4 gene has an unusual structure formed by 20 exons. A bacterial
      type PEPC gene was also identified in rice (Oryza sativa), stated as Osppc-b,
      therefore showing the presence of this type of PEPC in monocots. The phylogenetic
      analysis suggests that both plant-type and bacterial-type PEPCs diverged early
      during the evolution of plants from a common ancestor, probably the PEPC from
      gamma-proteobacteria. The diversity of plant-type PEPCs in C3, C4, and
      Crassulacean acid metabolism plants is indicative of the evolutionary success of
      the regulation by phosphorylation of this enzyme. Although at a low level, the
      bacterial-type PEPC genes are expressed in Arabidopsis and rice.

PMID- 12805625
TI  - The pyruvate decarboxylase1 gene of Arabidopsis is required during anoxia but not
      other environmental stresses.
AB  - Ethanolic fermentation is classically associated with flooding tolerance when
      plant cells switch from respiration to anaerobic fermentation. However, recent
      studies have suggested that fermentation also has important functions in the
      presence of oxygen, mainly in germinating pollen and during abiotic stress.
      Pyruvate decarboxylase (PDC), which catalyzes the first step in this pathway, is
      thought to be the main regulatory enzyme. Here, we characterize the PDC gene
      family in Arabidopsis. PDC is encoded by four closely related genes. By using
      real-time quantitative polymerase chain reaction, we determined the expression
      levels of each individual gene in different tissues, under normal growth
      conditions, and when the plants were subjected to anoxia or other environmental
      stress conditions. We show that PDC1 is the only gene induced under oxygen
      limitation among the PDC1 gene family and that a pdc1 null mutant is comprised in
      anoxia tolerance but not other environmental stresses. We also characterize the
      expression of the aldehyde dehydrogenase (ALDH) gene family. None of the three
      genes is induced by anoxia but ALDH2B7 reacts strongly to ABA application and
      dehydration, suggesting that ALDH may play a role in aerobic detoxification of
      acetaldehyde. We discuss the possible role of ethanolic fermentation as a robust
      back-up energy production pathway under adverse conditions when mitochondrial
      function is disturbed.

PMID- 12805624
TI  - Gene expression of the NO3- transporter NRT1.1 and the nitrate reductase NIA1 is
      repressed in Arabidopsis roots by NO2-, the product of NO3- reduction.
AB  - NRT1.1 and NIA1 genes, which encode a nitrate (NO3-) transporter and the minor
      isoform of NO3- reductase (NR), respectively, are overexpressed in roots of NR
      deficient mutants of Arabidopsis grown on nutrient solution containing NO3- and
      reduced N. The overexpression is found only in mutants with reduced NIA2
      activity, and disruption of the NIA1 gene alone has no effect on NRT1.1
      expression. Because the up-regulation of NRT1.1 and NIA1 is observed in N
      sufficient NR mutant plants, it cannot be related to a release of the general
      feedback repression exerted by the N status of the plant. Our data do not support
      the hypothesis of overinduction of these genes by an increased concentration of
      NO3- in tissues. Furthermore, although a control by external pH might contribute
      to the regulation of NRT1.1, changes in external pH due to lack of NR activity
      cannot alone explain the up-regulation of both genes. The stimulation of NRT1.1
      and NIA1 in NR mutants in these conditions suggests that NR activity is able to
      repress directly the expression of both genes independently of the availability
      of reduced N metabolites in wild-type plants. Accordingly, nitrite (NO2-)
      strongly represses NRT1.1 and NIA1 transcript accumulation in the roots. This
      effect is rapid, specific, and reversible. Furthermore, transport studies on
      plants exposed to NO2- show that down-regulation of the NRT1.1 gene is associated
      with a decrease in NO3- influx. These results indicate that feedback regulation
      of genes of NO3- assimilation relies not only on the repression exerted by
      reduced N metabolites, such as NH4+ or amino acids, but may also involve the
      action of NO2- as a regulatory signal.

PMID- 12805626
TI  - Physiological and molecular assessment of altered expression of Hsc70-1 in
      Arabidopsis. Evidence for pleiotropic consequences.
AB  - Hsp70s function as molecular chaperones. The protective chaperone activities of
      hsp70 help to confer tolerance to heat, glucose deprivation, and drought.
      Overexpression of hsp70s in many organisms correlates with enhanced
      thermotolerance, altered growth, and development. To better understand the roles
      of hsp70 proteins in Arabidopsis, the molecular and physiological consequences of
      altered expression of the major heat shock cognate, Hsc70-1, were analyzed.
      Extensive efforts to achieve underexpression of Hsc70-1 mRNA using a full-length
      antisense cDNA resulted in no viable transgenic plants, suggesting that reduced
      expression is lethal. Constitutive overexpression of Hsc70-1 also appeared to be
      deleterious to viability, growth, and development because fewer transformants
      were recovered, and most were dwarfed with altered root systems. Despite being
      dwarfed, the overexpression plants progressed normally through four selected
      developmental stages. Heat treatment revealed that Hsc70-1 overexpression plants
      were more tolerant to heat shock (44 degrees C for 10 min). The elevated basal
      levels of HSC70-1 in transgenic plants led to delayed heat shock response of
      several heat shock genes. The data in this study suggest that tight regulation of
      Hsc70-1 expression is critical for the viability of Arabidopsis and that the
      functions of HSC70-1 contribute to optimum growth, development, thermotolerance,
      and regulation of the heat shock response.

PMID- 12805627
TI  - Strategies for development of functionally equivalent promoters with minimum
      sequence homology for transgene expression in plants: cis-elements in a novel DNA
      context versus domain swapping.
AB  - The cauliflower mosaic virus 35S (35S) promoter has been extensively used for the
      constitutive expression of transgenes in dicotyledonous plants. The repetitive
      use of the same promoter is known to induce transgene inactivation due to
      promoter homology. As a way to circumvent this problem, we tested two different
      strategies for the development of synthetic promoters that are functionally
      equivalent but have a minimum sequence homology. Such promoters can be generated
      by (a) introducing known cis-elements in a novel or synthetic stretch of DNA or
      (b) "domain swapping," wherein domains of one promoter can be replaced with
      functionally equivalent domains from other heterologous promoters. We evaluated
      the two strategies for promoter modifications using domain A (consisting of
      minimal promoter and subdomain A1) of the 35S promoter as a model. A set of
      modified 35S promoters were developed whose strength was compared with the 35S
      promoter per se using beta-glucuronidase as the reporter gene. Analysis of the
      expression of the reporter gene in transient assay system showed that domain
      swapping led to a significant fall in promoter activity. In contrast, promoters
      developed by placing cis-elements in a novel DNA context showed levels of
      expression comparable with that of the 35S. Two promoter constructs Mod2A1T and
      Mod3A1T were then designed by placing the core sequences of minimal promoter and
      subdomain A1 in divergent DNA sequences. Transgenics developed in tobacco
      (Nicotiana tabacum) with the two constructs and with 35S as control were used to
      assess the promoter activity in different tissues of primary transformants.
      Mod2A1T and Mod3A1T were found to be active in all of the tissues tested, at
      levels comparable with that of 35S. Further, the expression of the Mod2A1T
      promoter in the seedlings of the T1 generation was also similar to that of the
      35S promoter. The present strategy opens up the possibility of creating a set of
      synthetic promoters with minimum sequence homology and with expression levels
      comparable with the wild-type prototype by modifying sequences present between
      cis-elements for transgene expression in plants.

PMID- 12805628
TI  - Systemic gene expression in Arabidopsis during an incompatible interaction with
      Alternaria brassicicola.
AB  - Pathogen challenge can trigger an integrated set of signal transduction pathways,
      which ultimately leads to a state of "high alert," otherwise known as systemic or
      induced resistance in tissue remote to the initial infection. Although large
      scale gene expression during systemic acquired resistance, which is induced by
      salicylic acid or necrotizing pathogens has been previously reported using a
      bacterial pathogen, the nature of systemic defense responses triggered by an
      incompatible necrotrophic fungal pathogen is not known. We examined
      transcriptional changes that occur during systemic defense responses in
      Arabidopsis plants inoculated with the incompatible fungal pathogen Alternaria
      brassicicola. Substantial changes (2.00-fold and statistically significant) were
      demonstrated in distal tissue of inoculated plants for 35 genes (25 up-regulated
      and 10 down-regulated), and expression of a selected subset of systemically
      expressed genes was confirmed using real-time quantitative polymerase chain
      reaction. Genes with altered expression in distal tissue included those with
      putative functions in cellular housekeeping, indicating that plants modify these
      vital processes to facilitate a coordinated response to pathogen attack.
      Transcriptional up-regulation of genes encoding enzymes functioning in the beta
      oxidation pathway of fatty acids was particularly interesting. Transcriptional up
      regulation was also observed for genes involved in cell wall synthesis and
      modification and genes putatively involved in signal transduction. The results of
      this study, therefore, confirm the notion that distal tissue of a pathogen
      challenged plant has a heightened preparedness for subsequent pathogen attacks.

PMID- 12805629
TI  - An Arabidopsis inositol 5-phosphatase gain-of-function alters abscisic acid
      signaling.
AB  - Signals can be perceived and amplified at the cell membrane by receptors coupled
      to the production of a variety of second messengers, including inositol 1,4,5
      trisphosphate (IP3). We previously have identified 15 putative inositol 5
      phosphatases (5PTases) from Arabidopsis and shown that At5PTase1 can hydrolyze
      IP3. To determine whether At5PTase1 can terminate IP3-mediated signaling, we
      analyzed transgenic plants ectopically expressing At5PTase1. Stomata from leaves
      of At5PTase1 transgenic plants were abscisic acid (ABA) and light insensitive,
      and ABA induction of genes was delayed. Quantification of IP3 in plants exposed
      to ABA indicated that ABA induced two IP3 increases in wild-type plants. Both of
      these IP3 increases were reduced in At5PTase1 transgenic plants, indicating that
      IP3 may be necessary for stomatal closure and temporal control of ABA-induced
      gene expression. To determine if ABA could induce expression of At5PTase1, we
      examined RNA and protein levels of At5PTase1 in wild-type plants exposed to ABA.
      Our results indicate that At5PTase1 is up-regulated in response to ABA. This is
      consistent with At5PTase1 acting as a signal terminator of ABA signaling.

PMID- 12805630
TI  - A role for the GCC-box in jasmonate-mediated activation of the PDF1.2 gene of
      Arabidopsis.
AB  - The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a
      marker for characterization of the jasmonate-dependent defense responses. Here,
      using PDF1.2 promoter-deletion lines linked to the beta-glucoronidase-reporter
      gene, we examined putative promoter elements associated with jasmonate-responsive
      expression of this gene. Using stably transformed plants, we first characterized
      the extended promoter region that positively regulates basal expression from the
      PDF1.2 promoter. Second, using promoter deletion constructs including one from
      which the GCC-box region was deleted, we observed a substantially lower response
      to jasmonate than lines carrying this motif. In addition, point mutations
      introduced into the core GCC-box sequence substantially reduced jasmonate
      responsiveness, whereas addition of a 20-nucleotide-long promoter element
      carrying the core GCC-box and flanking nucleotides provided jasmonate
      responsiveness to a 35S minimal promoter. Taken together, these results indicated
      that the GCC-box plays a key role in conferring jasmonate responsiveness to the
      PDF1.2 promoter. However, deletion or specific mutations introduced into the core
      GCC-box did not completely abolish the jasmonate responsiveness of the promoter,
      suggesting that the other promoter elements lying downstream from the GCC-box
      region may also contribute to jasmonate responsiveness. In other experiments, we
      identified a jasmonate- and pathogen-responsive ethylene response factor
      transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis
      plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase)
      genes, all of which contain a GCC-box sequence in their promoters. Our results
      suggest that in addition to their roles in regulating ethylene-mediated gene
      expression, ethylene response factors also appear to play important roles in
      regulating jasmonate-responsive gene expression, possibly via interaction with
      the GCC-box.

PMID- 12805631
TI  - Tensile properties of Arabidopsis cell walls depend on both a xyloglucan cross
      linked microfibrillar network and rhamnogalacturonan II-borate complexes.
AB  - The mechanical properties of plant organs depend upon anatomical structure, cell
      cell adhesion, cell turgidity, and the mechanical properties of their cell walls.
      By testing the mechanical responses of Arabidopsis mutants, it is possible to
      deduce the contribution that polymers of the cell wall make to organ strength. We
      developed a method to measure the tensile parameters of the expanded regions of
      turgid or plasmolyzed dark-grown Arabidopsis hypocotyls and applied it to the
      fucose biosynthesis mutant mur1, the xyloglucan glycosyltransferase mutants mur2
      and mur3, and the katanin mutant bot1. Hypocotyls from plants grown in the
      presence of increasing concentrations of dichlorobenzonitrile, an inhibitor of
      cellulose synthesis, were considerably weakened, indicating the validity of our
      approach. In order of decreasing strength, the hypocotyls of mur2 > bot1 and mur1
      > mur3 were each found to have reduced strength and a proportionate reduction in
      modulus compared with wild type. The tensile properties of the hypocotyls and of
      the inflorescence stems of mur1 were rescued by growth in the presence of high
      concentrations of borate, which is known to cross-link the pectic component
      rhamnogalacturonan II. From comparison of the mechanical responses of mur2 and
      mur3, we deduce that galactose-containing side chains of xyloglucan make a major
      contribution to overall wall strength, whereas xyloglucan fucosylation plays a
      comparatively minor role. We conclude that borate-complexed rhamnogalacturonan II
      and galactosylated xyloglucan contribute to the tensile strength of cell walls.

PMID- 12805632
TI  - Na+/H+ exchange activity in the plasma membrane of Arabidopsis.
AB  - In plants, Na+/H+ exchangers in the plasma membrane are critical for growth in
      high levels of salt, removing toxic Na+ from the cytoplasm by transport out of
      the cell. The molecular identity of a plasma membrane Na+/H+ exchanger in
      Arabidopsis (SOS1) has recently been determined. In this study, immunological
      analysis provided evidence that SOS1 localizes to the plasma membrane of leaves
      and roots. To characterize the transport activity of this protein, purified
      plasma membrane vesicles were isolated from leaves of Arabidopsis. Na+/H+
      exchange activity, monitored as the ability of Na to dissipate an established pH
      gradient, was absent in plants grown without salt. However, exchange activity was
      induced when plants were grown in 250 mm NaCl and increased with prolonged salt
      exposure up to 8 d. H+-coupled exchange was specific for Na, because chloride
      salts of other monovalent cations did not dissipate the pH gradient. Na+/H+
      exchange activity was dependent on Na (substrate) concentration, and kinetic
      analysis indicated that the affinity (apparent Km) of the transporter for Na+ is
      22.8 mm. Data from two experimental approaches supports electroneutral exchange
      (one Na+ exchanged for one proton): (a) no change in membrane potential was
      measured during the exchange reaction, and (b) Na+/H+ exchange was unaffected by
      the presence or absence of a membrane potential. Results from this research
      provide a framework for future studies into the regulation of the plant plasma
      membrane Na+/H+ exchanger and its relative contribution to the maintenance of
      cellular Na+ homeostasis during plant growth in salt.

PMID- 12805633
TI  - Differential regulation of two Arabidopsis type III phosphatidylinositol 4-kinase
      isoforms. A regulatory role for the pleckstrin homology domain.
AB  - Here, we compare the regulation and localization of the Arabidopsis type III
      phosphatidylinositol (PtdIns) 4-kinases, AtPI4Kalpha1 and AtPI4Kbeta1, in
      Spodoptera frugiperda (Sf9) insect cells. We also explore the role of the
      pleckstrin homology (PH) domain in regulating AtPI4Kalpha1. Recombinant kinase
      activity was found to be differentially sensitive to PtdIns-4-phosphate
      (PtdIns4P), the product of the reaction. The specific activity of AtPI4Kalpha1
      was inhibited 70% by 0.5 mm PtdIns4P. The effect of PtdIns4P was not simply due
      to charge because AtPI4Kalpha1 activity was stimulated approximately 50% by equal
      concentrations of the other negatively charged lipids, PtdIns3P, phosphatidic
      acid, and phosphatidyl-serine. Furthermore, inhibition of AtPI4Kalpha1 by
      PtdIns4P could be alleviated by adding recombinant AtPI4Kalpha1 PH domain, which
      selectively binds to PtdIns4P (Stevenson et al., 1998). In contrast, the specific
      activity of AtPI4Kbeta1, which does not have a PH domain, was stimulated 2-fold
      by PtdIns4P but not other negatively charged lipids. Visualization of green
      fluorescent protein fusion proteins in insect cells revealed that AtPI4Kalpha1
      was associated primarily with membranes in the perinuclear region, whereas
      AtPI4Kbeta1 was in the cytosol and associated with small vesicles throughout the
      cytoplasm. Expression of AtPI4Kalpha1 without the PH domain in the insect cells
      compromised PtdIns 4-kinase activity and caused mislocalization of the kinase.
      The green fluorescent protein-PH domain alone was associated with intracellular
      membranes and the plasma membrane. In vitro, the PH domain appeared to be
      necessary for association of AtPI4Kalpha1 with fine actin filaments. These
      studies support the idea that the Arabidopsis type III PtdIns 4-kinases are
      responsible for distinct phosphoinositide pools.

PMID- 12805634
TI  - Arabidopsis contains a large superfamily of acyl-activating enzymes. Phylogenetic
      and biochemical analysis reveals a new class of acyl-coenzyme a synthetases.
AB  - Acyl-activating enzymes are a diverse group of proteins that catalyze the
      activation of many different carboxylic acids, primarily through the formation of
      a thioester bond. This group of enzymes is found in all living organisms and
      includes the acyl-coenzyme A synthetases, 4-coumarate:coenzyme A ligases,
      luciferases, and non-ribosomal peptide synthetases. The members of this
      superfamily share little overall sequence identity, but do contain a 12-amino
      acid motif common to all enzymes that activate their acid substrates using ATP
      via an enzyme-bound adenylate intermediate. Arabidopsis possesses an acyl
      activating enzyme superfamily containing 63 different genes. In addition to the
      genes that had been characterized previously, 14 new cDNA clones were isolated as
      part of this work. The protein sequences were compared phylogenetically and
      grouped into seven distinct categories. At least four of these categories are
      plant specific. The tissue-specific expression profiles of some of the genes of
      unknown function were analyzed and shown to be complex, with a high degree of
      overlap. Most of the plant-specific genes represent uncharacterized aspects of
      carboxylic acid metabolism. One such group contains members whose enzymes
      activate short- and medium-chain fatty acids. Altogether, the results presented
      here describe the largest acyl-activating enzyme family present in any organism
      thus far studied at the genomic level and clearly indicate that carboxylic acid
      activation metabolism in plants is much more complex than previously thought.

PMID- 12805635
TI  - Characterization of green seed, an enhancer of abi3-1 in Arabidopsis that affects
      seed longevity.
AB  - Seeds are usually stored in physiological conditions in which they gradually lose
      their viability and vigor depending on storage conditions, storage time, and
      genotype. Very little is known about the underlying genetics of seed storability
      and seed deterioration. We analyzed a mutant in Arabidopsis disturbed in seed
      storability. This mutant was isolated as a grs (green-seeded) mutant in an abi3-1
      (abscisic acid 3) mutant background. Genetic and physiological characterization
      showed that the monogenic grs mutant was not visibly green seeded and mapped on
      chromosome 4. This enhancer mutation did not affect the ABA sensitivity of seed
      germination or seed dormancy but was found to affect seed storability and
      seedling vigor. Seed storability was assessed in a controlled deterioration test,
      in which the germination capacity of the mutant decreased with the duration of
      the treatment. The decrease in viability and vigor was confirmed by storing the
      seeds in two relative humidities (RHs) for a prolonged period. At 60% RH, the
      mutant lost germinability, but storage at 32% RH showed no decrease of
      germination although seed vigor decreased. The decrease in viability and vigor
      could be related to an increase in conductivity, suggesting membrane
      deterioration. This was not affected by light conditions during imbibition,
      expected to influence the generation of active oxygen species. During seed
      maturation, ABI3 regulates several processes: acquiring dormancy and long-term
      storability and loss of chlorophyll. Our results indicate that GRS is a common
      regulator in the latter two but not of dormancy/germination.

PMID- 12805636
TI  - Ethylene modulates root-wave responses in Arabidopsis.
AB  - When stimulated to bend downward by being held at 45 degrees off vertical but
      unable to penetrate into agar-based media, Arabidopsis roots develop waving and
      looping growth patterns. Here, we demonstrate that ethylene modulates these
      responses. We determined that agar-containing plates sealed with low-porosity
      film generate abiotic ethylene concentrations of 0.1 to 0.3 microL L(-1), whereas
      in plates wrapped with porous tape, ethylene remains at trace levels. We
      demonstrate that exogenous ethylene at concentrations as low as a few nanoliters
      per liter modulates root waving, root growth direction, and looping but through
      partly different mechanisms. Nutrients and Suc modify the effects of ethylene on
      root waving. Thus, ethylene had little effect on temporal wave frequency when
      nutrients were omitted but reduced it significantly on nutrient-supplemented
      agar. Suc masked the ethylene response. Ethylene consistently suppressed the
      normal tendency for roots of Landsberg erecta to skew to the right as they grow
      against hard-agar surfaces and also generated righthanded petiole twisting.
      Furthermore, ethylene suppressed root looping, a gravity-dependent growth
      response that was enhanced by high nutrient and Suc availability. Our work
      demonstrates that cell file twisting is not essential for root waving or skewing
      to occur. Differential flank growth accounted for both the extreme root waving on
      zero-nutrient plates and for root skewing. Root twisting was nutrient-dependent
      and was thus strongly associated with the looping response. The possible role of
      auxin transport in these responses and the involvement of circadian rhythms are
      discussed.

PMID- 12805637
TI  - A conserved 19-amino acid synthetic peptide from the carboxy terminus of
      phosphoenolpyruvate carboxylase inhibits the in vitro phosphorylation of the
      enzyme by the calcium-independent phosphoenolpyruvate carboxylase kinase.
AB  - Higher plant phosphoenolpyruvate carboxylase (PEPC) is subject to in vivo
      phosphorylation of a regulatory serine located in the N-terminal domain of the
      protein. Studies using synthetic peptide substrates and mutated phosphorylation
      domain photosynthetic PEPC (C4 PEPC) suggested that the interaction of
      phosphoenolpyruvate carboxylase kinase (PEPCk) with its target was not restricted
      to this domain. However, no further information was available as to where PEPCk
      C4 PEPC interactions take place. In this work, we have studied the possible
      interaction of the conserved 19-amino acid C-terminal sequence of sorghum
      (Sorghum vulgare Pers cv Tamaran) C4 PEPC with PEPCk. In reconstituted assays, a
      C-terminal synthetic peptide containing this sequence (peptide C19) was found to
      inhibit the phosphorylation reaction by the partially purified Ca2+-independent
      PEPCk (50% inhibition of initial activity = 230 microm). This effect was highly
      specific because peptide C19 did not alter C4 PEPC phosphorylation by either a
      partially purified sorghum leaf Ca2+-dependent protein kinase or the catalytic
      subunit of mammalian protein kinase A. In addition, the Ca2+-independent PEPCk
      was partially but significantly retained in affinity chromatography using a
      peptide C19 agarose column. Because peptide C15 (peptide C19 lacking the last
      four amino acids, QNTG) also inhibited C4 PEPC phosphorylation, it was concluded
      that the amino acid sequence downstream from the QNTG motif was responsible for
      the inhibitory effect. Specific antibodies raised against peptide C19 revealed
      that native C4 PEPC could be in two different conformational states. The results
      are discussed in relation with the reported crystal structure of the bacterial
      (Escherichia coli) and plant (maize [Zea mays]) enzymes.

PMID- 12805638
TI  - Analysis of the molecular basis of flowering time variation in Arabidopsis
      accessions.
AB  - Allelic variation at the FRI (FRIGIDA) and FLC (FLOWERING LOCUS C) loci are major
      determinants of flowering time in Arabidopsis accessions. Dominant alleles of FRI
      confer a vernalization requirement causing plants to overwinter vegetatively.
      Many early flowering accessions carry loss-of-function fri alleles containing one
      of two deletions. However, some accessions categorized as early flowering types
      do not carry these deletion alleles. We have analyzed the molecular basis of
      earliness in five of these accessions: Cvi, Shakhdara, Wil-2, Kondara, and Kz-9.
      The Cvi FRI allele carries a number of nucleotide differences, one of which
      causes an in-frame stop codon in the first exon. The other four accessions
      contain nucleotide differences that only result in amino acid substitutions.
      Preliminary genetic analysis was consistent with Cvi carrying a nonfunctional FRI
      allele; Wil-2 carrying either a defective FRI or a dominant suppressor of FRI
      function; and Shakhdara, Kondara, and Kz-9 carrying a functional FRI allele with
      earliness being caused by allelic variation at other loci including FLC. Allelic
      variation at FLC was also investigated in a range of accessions. A novel
      nonautonomous Mutator-like transposon was found in the weak FLC allele in
      Landsberg erecta, positioned in the first intron, a region required for normal
      FLC regulation. This transposon was not present in FLC alleles of most other
      accessions including Shakhdara, Kondara, or Kz-9. Thus, variation in Arabidopsis
      flowering time has arisen through the generation of nonfunctional or weak FRI and
      FLC alleles.

PMID- 12805639
TI  - Risk assessment of acrylamide in foods.
AB  - Daily mean intakes of acrylamide present in foods and coffee in a limited
      Norwegian exposure assessment study have been estimated to be 0.49 and 0.46
      microg per kg body weight in males and females, respectively. Testicular
      mesotheliomas and mammary gland adenomas have consistently been found in 2-year
      drinking water rat cancer studies with acrylamide. Acrylamide also shows
      initiating activity in mouse skin after systemic administration. Since acrylamide
      is converted to the mutagenic metabolite glycidamide and forms adducts to
      hemoglobin in rodents and humans, the tumorigenic endpoints in rats were assumed
      to be an expression of acrylamide genotoxicity. Using the default linear
      extrapolation methods LED10 and T25, the lifetime cancer hazard after lifelong
      exposure to 1 microg acrylamide per kg body weight per day, scaled to humans, was
      calculated to be, on average, 1.3 x 10-3. Using this hazard level and correlating
      it with the exposure estimates, a lifetime cancer risk related to daily intake of
      acrylamide in foods for 70 years in males was calculated to be 0.6 x 10-3,
      implying that 6 out of 10,000 individuals may develop cancer due to acrylamide.
      For females, the risk values were slightly lower. It must be emphasized that this
      risk assessment is conservative. A number of processes may result in nonlinearity
      of the dose-response relationships for acrylamide carcinogenicity in the low-dose
      region, including detoxication reactions, cell cycle arrest, DNA repair,
      apoptosis, and immune surveillance. Thus, the true risk levels related to
      acrylamide intake may be considerably lower.

PMID- 12805640
TI  - Motorcycle exhaust particulates enhance vasoconstriction in organ culture of rat
      aortas and involve reactive oxygen species.
AB  - The effects of motorcycle exhaust particulate on vasoconstriction were determined
      using rat thoracic aortas under organ culture conditions treated with organic
      extracts of motorcycle exhaust particulate from a two-stroke engine. The
      motorcycle exhaust particulate extract (MEPE) induced a concentration-dependent
      enhancement of vasoconstriction elicited by phenylephrine in the organ cultures
      of both intact and endothelium-denuded aortas for 18 h. Nifedipine (an L-type
      Ca2+ channel blocker), manganese acetate (an inorganic Ca2+ channel blocker), and
      staurosporine (a nonselective protein kinase C inhibitor), but not the selective
      protein kinase C inhibitor chelerythrine, inhibited the enhancement of
      vasoconstriction by MEPE. Staurosporine has also been reported as a myosin light
      chain kinase (MLCK) inhibitor, so we tested whether the MLCK pathway was involved
      in the effect of MEPE. The results showed that ML-9 (a selective MLCK inhibitor)
      could inhibit the enhancement of vasoconstriction by MEPE. The phosphorylation of
      a 20-kDa myosin light chain in a primary culture of rat vascular smooth muscle
      cells was also enhanced by MEPE. Moreover, we also examined the role of reactive
      oxygen species (ROS) in the stimulatory effect of MEPE on vasoconstriction. The
      antioxidant N-acetylcysteine significantly inhibited the enhancement of
      vasoconstriction by MEPE. A time-dependent increase in ROS production by MEPE was
      also detected in primary cultures of vascular smooth muscle cells. These results
      indicate that MEPE induces a marked enhancement of vasoconstriction in aortas
      under organ culture conditions and imply that a ROS-Ca2+-MLCK pathway may be
      involved in this MEPE-induced response.

PMID- 12805641
TI  - Prolonged ethanol ingestion enhances benzene myelotoxicity and lowers urinary
      concentrations of benzene metabolite levels in CD-1 male mice.
AB  - Benzene toxicity is attributed to its metabolism, which is primarily mediated by
      the ethanol-inducible cytochrome P450 2E1 isoform (CYP2E1). The present study
      investigated the myelotoxicity and urinary concentrations of major benzene
      metabolites in adult CD-1 male mice treated with low levels of benzene vapors,
      ethanol, or a combination of the two. Groups of ethanol-treated (5% in a Lieber
      DeCarli liquid diet, 3 weeks) or pair-fed control mice were exposed to 10 ppm
      benzene, 6 h per day, 5 days per week for 2 weeks, starting from the second week
      of ethanol administration. On the last day of treatment, the number of early and
      late erythroid progenitors (BFU-E and CFU-E) was reduced by 55%, while the number
      of granulocyte/macrophage progenitors (CFU-GM) was reduced by 36% in benzene
      treated mice. Ethanol lowered the CFU-E, BFU-E, and CFU-GM colony formation by
      33, 28, and 12%, respectively. In animals coexposed to benzene and ethanol, the
      CFU-E colony counts were decreased by 70%, the BFU-E by 80%, and the CFU-GM by
      45%. Phenol (Ph), hydroquinone (HQ), catechol (Cat), and trans,trans-muconic acid
      (MA) were measured by HPLC-UV in urine samples collected weekly during the last 6
      h benzene/air exposure session. In benzene-exposed mice urinary metabolite levels
      peaked at the end of the first week of treatment (microg/kg body weight (bw): Ph:
      4931 +/- 1055; Cat: 109 +/- 17; HQ: 784 +/- 137; MA: 534 +/- 92) and
      significantly decreased at the end of the second week (microg/kg bw: Ph: 3909 +/-
      984; Cat: 82 +/- 24; HQ: 337 +/- 72; MA: 235 +/- 55). In mice given benzene and
      ethanol, the urinary levels of Ph, Cat, HQ, and MA were significantly lower than
      those measured in the group given benzene alone. The urinary levels of Ph and Cat
      showed a decreasing trend, again, from the first to the second week of benzene
      exposure. These data indicate that chronic ethanol ingestion exacerbates benzene
      myelotoxicity and, in addition, reduces the urinary excretion of benzene
      metabolites in mice, suggesting that the influence of ethanol intake should be
      considered carefully in biomonitoring benzene exposure.

PMID- 12805642
TI  - Combined in situ and in vitro assessment of the estrogenic activity of sewage and
      surface water samples.
AB  - In order to investigate the estrogenic activities of two municipal sewage
      treatment plant (STP; sites A and B) effluents and of Rhine water sampled at
      Worms (site C; Rhine-Neckar triangle, Germany), data from in situ experiments
      measuring hepatic vitellogenin expression from caged rainbow trout (Oncorhynchus
      mykiss) were compared with data from in vitro bioassays (yeast estrogen screen
      [YES], ER luciferase assay with HEK 293 cells [HEK], primary rainbow trout
      hepatocytes [PH]) and chemical analysis. Three sampling campaigns were carried
      out at each site between November 2000 and September 2001. Vitellogenin (VTG)
      mRNA expression in male rainbow trout exposed for two weeks ranged from 3 +/- 5
      to 619 +/- 188 and from 226 +/- 38 to 3373 +/- 1958 pg/microg total RNA at sites
      A and B, respectively. E2-equivalents obtained from the in vitro bioassays gave
      values up to 0.21 +/- 0.04 nM (57.3 +/- 10.2 ng/l, PH), 0.07 +/- 0.03 nM (20.2 +/
      6.9 ng/l; YES) and 0.008 +/- 0.002 nM (2.1 +/- 0.7 ng/l; HEK). In contrast, in
      one-year-old rainbow trout exposed at site C, no VTG-mRNA induction could be
      observed after two weeks of exposure. In vitro bioassays (YES, HEK, PH) indicated
      estrogenic activity at site C, which, however, was lower than at the investigated
      STP effluents. Chemical analysis of representative water samples from site A
      identified steroidal estrogens up to 5.6 ng/l 17beta-estradiol (E2), 19 ng/l
      estrone as well as 1.5 ng/l 17alpha-ethinylestradiol. Furthermore, the sum of
      fecal- and phytosteroids, resorcyclic lactones, and flavonoid concentrations were
      280 (A) and 1.200 ng/l (B). In addition, site C (river Rhine) contained 3.9 ng/l
      E2 and 250 ng/l of fecal- and phytosteroids, respectively. Thus, STP effluents
      and Rhine water contain biologically relevant concentrations of estrogenic
      compounds, the activity of which can be detected by means of various bioassays.

PMID- 12805643
TI  - Proliferative effects of estradiol, progesterone, and two CB congeners and their
      metabolites on gray seal (Halichoerus grypus) uterine myocytes in vitro.
AB  - Gray seal females living in the Baltic Sea have been found to exhibit a high
      prevalence of uterine leiomyomas. These animals are also known to accumulate
      lipid-soluble PCBs in their blubber. PCBs have documented endocrine-disrupting
      effects; to investigate whether the PCBs could be part of the genesis of uterine
      smooth muscle tumors in this species, gray seal myometrial cell cultures were
      exposed to two CBs and their metabolites, as well as to estradiol and
      progesterone, after which the effects were analyzed in terms of proliferative
      activity by measurements of BrdU absorbance and protein content. Progesterone was
      found to have an inhibitory effect, whereas one CB acted as a stimulant on the
      myometrial cell proliferation. One of the CB metabolites also seemed to have an
      inhibitory effect, although this could not be statistically verified. These
      results suggest that some CBs have effects on uterine myometrial cell
      proliferation in gray seals and, thus, may also take part in the growth
      regulation of uterine leiomyomas.

PMID- 12805644
TI  - The laminin binding protein p40 is involved in inducing limb abnormality of mouse
      fetuses as the effects of methoxyacetic acid treatment.
AB  - This study is intended to characterize a protein that is linked with mouse limb
      teratogenicity as the effects of methoxyacetic acid (MAA) treatment. A single
      dose of MAA (10 mmol/kg body weight) was given by gavage on gestation day (GD)
      11, whereas the control group were administered vehicle only. The pregnant mice
      were killed at 4 h after MAA treatment, and forelimb buds were isolated from both
      the control and treated group embryos. Proteins from forelimb buds GD 11 + 4 h,
      which were precipitated out using 40-60% ammonium sulfate, then were analyzed by
      two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-D
      SDS-PAGE) technique. The 2-D gels reveal one protein with 41.6 kDa and pI 6.4,
      which expression was downregulated after MAA treatment. Tentative protein
      identification via peptide mass database search and definitive protein
      identification via a primary sequence database search indicate that the protein
      matches exactly to 34/67 kDa laminin binding protein (LBP; P14206, SwissProt),
      which is encoded by p40 gene (MGI:105381). The identity was further verified by
      Western blotting with an antibody against the 67 kDa LBP. The results suggest
      that MAA treatment to pregnant mice downregulates the LBP-p40 in the forelimb
      buds.

PMID- 12805645
TI  - Compromised DNA repair enhances sensitivity of the yeast RNR3-lacZ genotoxicity
      testing system.
AB  - The RNR3-lacZ genotoxicity testing system was developed based on the induction of
      a Saccharomyces cerevisiae RNR3-lacZ reporter gene in response to a broad range
      of DNA-damaging agents. In order to enhance the sensitivity of the RNR3-lacZ
      system, several deletion mutant strains representing different repair pathways
      were created and examined for their effects on RNR3-lacZ expression. It was found
      that inactivation of different DNA repair pathways has profound effects on the
      DNA damage induction of RNR3 expression. Although deletion of MAG1 in the base
      excision repair pathway enhances the detection sensitivity to DNA-alkylating
      agents, and deletion of RAD2 in the nucleotide excision repair pathway enhances
      the detection sensitivity to ultraviolet and agents that produce bulky lesions,
      inactivation of genes involved in the recombination repair and postreplication
      repair variably reduces RNR3-lacZ induction. This study not only helps to
      establish a more sensitive genotoxicity testing system but also suggests that
      certain eukaryotic DNA repair pathways are required for gene regulation in
      response to DNA damage and probably serve as sensors in the signal transduction
      cascade.

PMID- 12805646
TI  - p38 Mitogen-activated protein kinase regulates Bax translocation in cyanide
      induced apoptosis.
AB  - Execution of cyanide-induced apoptosis is mediated by release of cytochrome c
      from mitochondria. To determine how cyanide initiates cytochrome c release, Bax
      translocation was investigated in primary cultures of cortical neurons. Under
      nonapoptotic (control) conditions, Bax resided predominantly in the cytoplasm.
      After 300-microM cyanide treatment for 1 h, Bax translocated to the mitochondria,
      as shown by immunocytochemical staining and subcellular fractionation; Western
      blot analysis confirmed "cytosol-to-mitochondria" translocation of Bax. Temporal
      analysis showed that Bax translocation preceded cytochrome c release from the
      mitochondria, which was initiated 3 h after cyanide treatment. In double
      immunofluorescence labeling for both Bax and cytochrome c, it was observed that
      cytochrome c was released only in cells showing Bax in mitochondria. The role of
      p38 mitogen-activated protein (MAP) kinase in Bax translocation was studied. The
      p38 MAP kinase was activated 30 min after cyanide, and its phosphorylation level
      of activity began to decrease 3 h later. SB203580, a p38 MAP kinase inhibitor,
      blocked translocation of Bax to mitochondria, whereas SB202474, a control
      peptide, had no effect on translocation. Inhibition of p38 MAP kinase by SB203580
      blocked all downstream effects of Bax translocation, including cytochrome c
      release, caspase activation, and internucleosomal DNA fragmentation. These
      results demonstrated that Bax translocation is critical for cyanide-induced
      cytochrome c release and that p38 MAP kinase regulates Bax translocation from
      cytosol to mitochondria.

PMID- 12805647
TI  - Repeated inhalation exposures to the bioactivated cytotoxicant naphthalene (NA)
      produce airway-specific Clara cell tolerance in mice.
AB  - Repeated exposures to bioactivated cytotoxicants such as naphthalene (NA) render
      the target population, Clara cells, resistant to further injury through a
      glutathione-dependent mechanism. The current studies were designed to test the
      hypothesis that the mechanism for tolerance is localized in Clara cells. We used
      three approaches to test this hypothesis. First, using airway explants from
      tolerant mice maintained in culture, we sought to determine if the mechanism of
      Clara cell tolerance was airway-specific. Second, using inhalation as the route
      of exposure, we sought to determine if Clara cells at all airways levels become
      tolerant to repeated inhalation exposures of NA. Third, by measuring gamma
      glutamylcysteine synthetase (gamma-GCS) activity and expression we determined if
      tolerance to inhaled NA resulted from shifts in phase-II metabolism. Our results
      indicate that Clara cells in explants from tolerant mice remained tolerant to NA
      injury in culture. When mice were exposed to repeated inhalation exposures of NA
      (15 ppm), we found that Clara cells at all airway levels became tolerant.
      Expression and activity analysis revealed that gamma-GCS, the rate-limiting
      enzyme in glutathione synthesis, is induced in tolerant Clara cells. Buthionine
      sulfoximine, a gamma-GCS inhibitor, was able to eliminate the resistance of these
      tolerant cells. We conclude: (1) the mechanism of NA tolerance in Clara cells is
      airway specific, (2) the specific mechanism allows Clara cells to become tolerant
      to NA vapor at levels relevant to human exposure, and (3) the mechanism of
      tolerance to inhaled NA is highly dependent on induction of the catalytic enzyme,
      gamma-GCS.

PMID- 12805648
TI  - In utero exposure to 1R4F reference cigarette smoke: evaluation of developmental
      toxicity.
AB  - The potential developmental effects of 1R4F reference cigarette smoke were
      examined using Sprague-Dawley rats exposed for 2 h/day, 7 days/week, by nose-only
      inhalation at target mainstream smoke concentrations of 150, 300, and 600 mg/m3
      total particulate matter (TPM). Males were exposed 4 weeks prior to and during
      mating, with females exposed 2 weeks prior to mating and during mating, and
      through gestation day (GD) 20. Sham controls received filtered air to simulate
      nose-only exposure, while cage controls were maintained untreated. Smoke exposure
      was confirmed through biomarker evaluation (parental: carboxyhemoglobin,
      nicotine, and cotinine; fetal: nicotine and cotinine). Characteristic cigarette
      smoke-related histopathologic changes including nasal epithelial hyperplasia and
      squamous metaplasia and pigmented macrophages in the lung were observed in all
      exposed parental groups. Maternal toxicity during gestation was indicated at
      smoke concentrations of 300 and 600 mg TPM/m3, where corrected total body weight
      gain was significantly (p </= 0.05) decreased compared to sham controls. Food
      consumption was unaffected. Mating performance was unaffected by exposure: 71-75%
      pregnant in sham or cage control groups compared to 66-76% pregnant in smoke
      exposed groups. Nicotine and cotinine were identified in the blood of fetuses
      from smoke-exposed dams on GD 20. Resorption rates, litter size, and sex ratio
      were equivalent among the groups. Fetal body weights at GD 20 were significantly
      reduced in the group exposed to 300 or 600 mg TPM/m3 compared to sham exposed
      controls. Developmental abnormalities were rare and sporadic in nature and the
      absence of a clear smoke concentration relationship suggested they were not
      related to cigarette smoke inhalation. Skeletal examinations revealed delayed
      ossification (supra occipital and sternebrae) in fetuses from dams exposed to 300
      or 600 mg TPM/m3 smoke. High concentrations of 1R4F cigarette smoke were not
      teratogenic. The methodology used for this study was able to detect a decrease in
      fetal birthweight and this approach may be a useful tool for cigarette
      evaluation.

PMID- 12805649
TI  - Oxidative DNA damage and repair in a cell lineage model of human proliferative
      breast disease (PBD).
AB  - Oxidative damage to DNA is thought to play a significant role in mutagenesis,
      aging, and cancer. Sensitivity to oxidative DNA damage and DNA repair efficiency
      were examined using a series of human breast epithelial cell lines-MCF-10A, MCF
      10AT, and MCF-10ATG3B-with progressively elevated Ras protein. Breast epithelial
      cells were treated with H2O2, in the absence and presence of the DNA-repair
      inhibitors hydroxyurea (HU) and cytosine arabinoside (Ara-C). DNA strand breaks
      were assessed by the mean olive tail moment (microm) using the alkaline single
      cell gel electrophoresis (Comet) assay. In untreated cells, the mean olive tail
      moment values were 4.3 +/- 0.7, 8.3 +/- 1.1, and 7.1 +/- 0.6 microm in the MCF
      10A, MCF-10AT, and MCF-10ATG3B cells, respectively. Five min H2O2 treatment
      produced concentration-dependent DNA damage, with the MCF-10A cells most
      susceptible and the tumorigenic MCF-10ATG3B cells the least susceptible.
      Treatment with 100 microM H2O2 resulted in approximately 17-, 6-, and 4.5-fold
      increases in mean olive tail moment values in the MCF-10A, MCF-10AT, and MCF
      10ATG3B cells, respectively, compared to untreated cells. The HCC1937 tumor cell
      line responded in a manner comparable to the MCF-10ATG3B cells treated with H2O2,
      HU/Ara-C pre-treatment resulted in a approximately 1.5-fold increase in olive
      tail moment values in all three cell lines. Protein levels of antioxidant
      enzymes, including catalase, copper/zinc superoxide dismutase (Cu/Zn SOD), and
      manganese SOD (MnSOD) were determined in order to examine a potential mechanism
      for increased resistance to H2O2-mediated DNA damage. Levels of these enzymes
      increased progressively, with highest expression in MCF-10ATG3B cells. Increased
      cellular resistance also coincided with marked decreases in p53 protein levels.
      These results demonstrate that, in this cell lineage, sensitivity to oxidative
      DNA damage by H2O2 decreases with tumorigenicity (i.e., MCF-10A vs. MCF-10ATG3B),
      and show that DNA repair, altered Ras, and p53 expression, or compensatory
      mechanisms involving elevated antioxidant enzymes are involved in mediating these
      effects.

PMID- 12805650
TI  - Effects of butyltin compounds on mitochondrial respiration and its relation to
      hepatotoxicity in mice and Guinea pigs.
AB  - Because the mechanisms responsible for the difference in toxicity between
      different experimental animal species remain unclear, the effects of tributyltin
      chloride (TBTC) and dibutyltin dichloride (DBTC) on mitochondrial respiration
      were compared among the livers of mice and guinea pigs in vitro and in vivo.
      Further, the levels of these butyltin compounds and their derivatives in the
      mitochondrial fractions of the hepatocytes were investigated in these animal
      species. Administration of TBTC and DBTC to mice resulted in the obvious
      elevation of serum enzymatic activities, as well as the inhibition of succinate
      linked State 3 respiration in hepatic mitochondria at 24 h after administration.
      On the other hand, these metal compounds failed to induce such hepatotoxicity or
      to inhibit mitochondrial respiration in guinea pigs. There was no significant
      difference between mice and guinea pigs in the IC50 (metal concentration observed
      in 50% inhibition of mitochondrial respiration) of TBTC and DBTC against the
      succinate-linked State 3 respiration of hepatic mitochondria in vitro, although
      the mitochondrial respiration of succinate-linked State 3 was inhibited in the
      liver of mice treated with the metals in vivo. The levels of total butyltin
      compounds in the mitochondrial fractions of hepatocytes were higher in the mice
      than in the guinea pigs, and the main butyltin compound in the mitochondrial
      fractions was DBTC in both species at 24 h after TBTC or DBTC administration. The
      amount of sulfhydryl groups, which were capable of binding with DBTC, in mice
      hepatic mitochondria was twice as large as that in guinea pigs, and the affinity
      of DBTC for the isolated hepatic mitochondria was higher in mice than in guinea
      pigs in vitro. These results suggested that the induction of hepatotoxicity by
      TBTC and DBTC in vivo was closely associated with the depression of mitochondrial
      respiration and that the difference in susceptibility to the metal-induced
      mitochondrial damages between mice and guinea pigs might result from the high
      affinity of butyltin compounds, in particular DBTC, for hepatic mitochondria in
      mice containing higher levels of sulfhydryl groups, compared with guinea pigs.

PMID- 12805651
TI  - Biologically motivated computational modeling of chloroform cytolethality and
      regenerative cellular proliferation.
AB  - Chloroform is a nongenotoxic-cytotoxic carcinogen in rodents. As such, events
      related to cytotoxicity are the driving force for cancer induction. In this paper
      we extended an existing physiologically based pharmacokinetic (PBPK) model for
      chloroform to describe a plausible mechanism linking the hepatic metabolism of
      chloroform to hepatocellular killing and regenerative proliferation. The key
      aspects of this mechanism are (1) the production of damage at a rate proportional
      to the rate of metabolism predicted by the PBPK model, (2) the saturable repair
      of the damage, (3) the stimulation of the cell death rate by damage, and (4) the
      stimulation of the cell division rate as a function of the difference between the
      control and exposed numbers of cells. This extension allows the simulation of the
      labeling index and comparison with labeling index data. Data from a previously
      published chloroform-inhalation study with female B6C3F1 mice that determined
      cytolethality and regenerative cellular proliferation following exposures of
      varying concentrations and exposure durations were used for model calibration.
      Both threshold and low-dose linear linkages between chloroform-induced damage and
      cell death rate provided visually good fits to the labeling index data after
      formal optimization of the adjustable parameters, and there was no statistical
      difference between the fits of the two models to the data. Biologically motivated
      computational modeling of chloroform-induced cytolethality and regenerative
      proliferation is a necessary step in the quantitative evaluation of the
      hypothesis that chloroform-stimulated cell proliferation predicts the rodent
      tumor response.

PMID- 12805652
TI  - Effect of methylmercury on midbrain cell proliferation during organogenesis:
      potential cross-species differences and implications for risk assessment.
AB  - 5'-bromodeoxyuridine (BrdU) labeling was employed to explore the effects of
      methylmercury (MeHg) on cell cycle kinetics in the developing rat midbrain during
      gestational days (GDs) 11 to 14. Contrary to what has been previously reported in
      mice, no effects of MeHg on cell cycle kinetics were observed up to embryonic
      brain concentrations of 3-4 microg/g. The absence of an effect was confirmed
      using stereology and counts of midbrain cell number. Treatment with colchicine,
      the positive control, resulted in significant effects on cell cycle kinetics in
      the developing rat midbrain. The parallelogram method, borrowed from genetic
      toxicology, was subsequently used to place the data obtained in the present study
      in the context of previously collected in vitroand in vivo data on MeHg
      developmental neurotoxicity. This required developing a common dose metric
      (microg Hg/g cellular material) to allow in vitro and in vivo study comparisons.
      Evaluation suggested that MeHg's effects on neuronal cell proliferation show a
      reasonable degree of concordance across mice, rats, and humans, spanning
      approximately an order of magnitude. Comparisons among the in vivo data suggest
      that humans are at least or more sensitive than the rodent and that mice may be a
      slightly better model for MeHg human developmental neurotoxicity than the rat.
      Such comparisons can provide both a quantitative and a qualitative framework for
      utilizing both in vivo and in vitro data in human health risk assessment.

PMID- 12805653
TI  - Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen
      receptor.
AB  - By using a yeast detection system for androgenic and antiandrogenic effects of
      chemicals, we identified bisphenol A (BPA) and nonylphenol (NP) as antiandrogens.
      In this study, we report molecular mechanisms for the antiandrogenic action of
      BPA and NP. In the ARhLBD-activating signal cointegrator 1 (ASC1) yeast two
      hybrid system, which reflects the androgen-dependent interaction between androgen
      receptor (AR) and its coactivator, ASC1, BPA and NP acted as potent AR
      antagonists comparable to a known strong antagonist, cyproterone acetate. Ligand
      competition assays revealed that [3H]5alpha-dihydroxytestosterone (DHT) binding
      to AR is inhibited a maximum of 30 and 40% at approximately 5 nM of NP and 50 nM
      of BPA, respectively. In addition, the nuclear translocation of green fluorescent
      protein (GFP)-AR fusion protein in the presence of testosterone was affected by
      the addition of BPA and NP, which cause rather dispersed distribution of GFP-AR
      between the nuclear and the cytoplasmic compartments. Furthermore, in transient
      transfection assays, BPA and NP inhibited androgen-induced AR transcriptional
      activity. Taken together, the results suggest that BPA and NP affect multiple
      steps of the activation and function of AR, thereby inhibiting the binding of
      native androgens to AR, AR nuclear localization, AR interaction with its
      coregulator, and its subsequent transactivation. These data may help us better
      understand the biological alterations induced by these environmental compounds.

PMID- 12805654
TI  - PCB 104-induced proinflammatory reactions in human vascular endothelial cells:
      relationship to cancer metastasis and atherogenesis.
AB  - Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that
      are known to induce carcinogenic and possibly atherogenic events. Recent evidence
      suggests that selected PCBs may be potent developmental agents of vascular
      inflammatory responses by inducing cellular oxidative stress and activating redox
      responsive transcription factors. Therefore, the aim of this paper is to
      investigate PCB-induced proinflammatory reactions in human vascular endothelial
      cells. To determine the proinflammatory effects, cellular oxidative stress and
      expression of genes encoding for monocyte chemoattractant protein-1 (MCP-1) and
      adhesion molecules, such as E-selectin and intercellular adhesion molecule-1
      (ICAM-1), were assessed in human umbilical vein endothelial cells (HUVEC) exposed
      to 2,2',4,6,6'-pentachlorobiphenyl (PCB 104), a representative of ortho
      substituted, non-coplanar PCB congeners. PCB 104 increased the oxidative stress
      in endothelial cells, as determined by the increased 2',7'-dichlorofluorescein
      (DCF) and rhodamine 123 fluorescence. In addition, PCB 104 markedly upregulated
      the expression of MCP-1, E-selectin, and ICAM-1 at both the mRNA and protein
      levels. These effects were time- and concentration-dependent. The maximum
      expression of inflammatory genes was observed in endothelial cells exposed to 20
      microM of PCB 104 for 1 or 2 h, depending on the specific gene. In addition, PCB
      104 elevated the adhesion of THP-1 cells (a human acute monocytic leukemia cell
      line) to endothelial cell monolayers. These results indicate that PCB 104 is a
      potent stimulant of inflammatory mediators in human vascular endothelial cells.
      We hypothesize that these proinflammatory processes may contribute to the
      development of cancer metastasis and/or atherogenesis in patients exposed to
      PCBs.

PMID- 12805655
TI  - Predicting neonatal perchlorate dose and inhibition of iodide uptake in the rat
      during lactation using physiologically-based pharmacokinetic modeling.
AB  - Perchlorate (ClO4-), a contaminant in drinking water, competitively inhibits
      active uptake of iodide (I-) into various tissues, including mammary tissue.
      During postnatal development, inhibition of I- uptake in the mammary gland and
      neonatal thyroid and the active concentration ClO4- in milk indicate a
      potentially increased susceptibility of neonates to endocrine disruption. A
      physiologically based pharmacokinetic (PBPK) model was developed to reproduce
      measured ClO4- distribution in the lactating and neonatal rat and predict
      resulting effects on I- kinetics from competitive inhibition at the sodium iodide
      symporter (NIS). Kinetic I- and ClO4- behavior in tissues with NIS (thyroid,
      stomach, mammary gland, and skin) was simulated with multiple subcompartments,
      Michaelis-Menten (M-M) kinetics and competitive inhibition. Physiological and
      kinetic parameters were obtained from literature and experiment. Systemic
      clearance and M-M parameters were estimated by fitting simulations to tissue and
      serum data. The model successfully describes maternal and neonatal thyroid,
      stomach, skin, and plasma, as well as maternal mammary gland and milk data after
      ClO4- exposure (from 0.01 to 10 mg/kg-day ClO4-) and acute radioiodide (2.1 to
      33,000 ng/kg I-) dosing. The model also predicts I- uptake inhibition in the
      maternal thyroid, mammary gland, and milk. Model simulations predict a
      significant transfer of ClO4- through milk after maternal exposure; approximately
      50% to 6% of the daily maternal dose at doses ranging from 0.01 to 10.0 mg ClO4
      /kg-day, respectively. Comparison of predicted dosimetrics across life-stages in
      the rat indicates that neonatal thyroid I- uptake inhibition is similar to the
      adult and approximately tenfold less than the fetus.

PMID- 12805659
TI  - Espionage scandal leads science news.
AB  - Two Japanese molecular biologists are charged with espionage in a case that could
      strain scientific relations between the U.S. and Japan, report both Nature and
      Science in their top stories this week.

PMID- 12805656
TI  - Activation of PPARalpha and PPARgamma by environmental phthalate monoesters.
AB  - Phthalate esters are widely used as plasticizers in the manufacture of products
      made of polyvinyl chloride. Mono-(2-ethylhexyl)-phthalate (MEHP) induces rodent
      hepatocarcinogenesis by a mechanism that involves activation of the nuclear
      transcription factor peroxisome proliferator-activated receptor-alpha
      (PPARalpha). MEHP also activates PPAR-gamma (PPARgamma), which contributes to
      adipocyte differentiation and insulin sensitization. Human exposure to other
      phthalate monoesters, including metabolites of di-n-butyl phthalate and butyl
      benzyl phthalate, is substantially higher than that of MEHP, prompting this
      investigation of their potential for PPAR activation, assayed in COS cells and in
      PPAR-responsive liver (PPARalpha) and adipocyte (PPARgamma) cell lines.
      Monobenzyl phthalate (MBzP) and mono-sec-butyl phthalate (MBuP) both increased
      the COS cell transcriptional activity of mouse PPARalpha, with effective
      concentration for half-maximal response (EC50) values of 21 and 63 microM,
      respectively. MBzP also activated human PPARalpha (EC50=30 microM) and mouse and
      human PPARgamma (EC50=75-100 microM). MEHP was a more potent PPAR activator than
      MBzP or MBuP, with mouse PPARalpha more sensitive to MEHP (EC50=0.6 microM) than
      human PPARalpha (EC50=3.2 microM). MEHP activation of PPARgamma required somewhat
      higher concentrations, EC50=10.1 microM (mouse PPARgamma) and 6.2 microM (human
      PPARgamma). No significant PPAR activation was observed with the monomethyl, mono
      n-butyl, dimethyl, or diethyl esters of phthalic acid. PPARalpha activation was
      verified in FAO rat liver cells stably transfected with PPARalpha, where
      expression of several endogenous PPARalpha target genes was induced by MBzP,
      MBuP, and MEHP. Similarly, activation of endogenous PPARgamma target genes was
      evidenced for all three phthalates by the stimulation of PPARgamma-dependent
      adipogenesis in the 3T3-L1 cell differentiation model. These findings demonstrate
      the potential of environmental phthalate monoesters for activation of rodent and
      human PPARs and may help to elucidate the molecular basis for the adverse health
      effects proposed to be associated with human phthalate exposure.

PMID- 12805660
TI  - Amylin: localization, effects on cerebral arteries and on local cerebral blood
      flow in the cat.
AB  - Amylin and adrenomedullin are two peptides structurally related to calcitonin
      gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal
      ganglia and cerebral blood vessels of the cat with immunocytochemistry and
      evaluated the role of amylin and adrenomedullin in the cerebral circulation by in
      vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve
      cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir);
      some of these also expressed amylin-ir but none adrenomedullin-ir. There were
      numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir.
      Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in
      the vessel walls. With RT-PCR and Real-Time-PCR we revealed the presence of mRNA
      for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying
      proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin,
      adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery.
      CGRP and amylin caused concentration-dependent relaxations at low concentrations
      of PGF 2alpha-precontracted segment (with or without endothelium) whereas only at
      high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP
      and amylin induced relaxations in a parallel fashion. In vivo studies of amylin,
      adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral
      blood flow as examined using laser Doppler flowmetry applied to the cerebral
      cortex of the alpha-chloralose-anesthetized cat. The responses to amylin and CGRP
      were blocked by CGRP8-37. The studies suggest that there is a functional sub-set
      of amylin-containing trigeminal neurons which probably act via CGRP receptors.

PMID- 12805661
TI  - Emerging technologies to control oocyte apoptosis are finally treading on fertile
      ground.
AB  - As the medical community strives to improve on the efficacy of anticancer
      treatments, a critical issue not to be overlooked since the overall quantity of
      life has been substantially increased in many cancer survivors is the quality of
      that life post-therapy. Indeed, one of the most worrisome side effects of
      conventional cancer treatments is damage to the gonads. This problem is
      compounded in females since the ovaries, unlike the testes, are incapable of germ
      cell renewal in postnatal life. As a consequence, the inappropriate destruction
      of female germ cells (oocytes) following exposure to chemotherapeutic drugs and
      radiation is irreparable, often leading to premature menopause and infertility .
      Considering recent estimates that 1 in 52 human females between birth and age 39
      (i.e., the pre-reproductive and reproductive years) will be diagnosed with, and
      presumably treated for, cancer , new strategies to minimize or prevent gonadal
      damage during such treatments would have a profound positive impact on millions
      of lives.

PMID- 12805662
TI  - New biochemical pathway may control erection.
AB  - Thirty million men in the U.S. suffer from erectile dysfunction (ED) defined by
      their inability to achieve or maintain a penile erection sufficient for
      intercourse. An unestimated number of women also suffer from sexual dysfunction
      resulting from many of the same causes that lead to ED in men. There are a
      variety of treatments available for ED including intracavernosal injection,
      transurethral therapy, surgery, vacuum therapy, and oral medication.
      Unfortunately, not all patients benefit from these currently available forms of
      therapy, and side effects are not uncommon. Sildenafil (Viagra) has been a highly
      successful drug for the treatment of ED but it does not work in all men . Some
      may experience a variety of side effects, and Viagra is contraindicated to some
      cardiac medications. These problems point to the need for new and different
      approaches to the treatment of sexual problems.

PMID- 12805663
TI  - Spatial positioning of RET and H4 following radiation exposure leads to tumor
      development.
AB  - Exposure to ionizing radiation is a well-known risk factor for a number of human
      cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many
      others. Although it has been known for a long time that radiation exposure to the
      cell results in extensive DNA damage, including double strand DNA breaks, the
      exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a
      large increase in incidence of thyroid cancer was observed in children exposed to
      radiation after the Chernobyl nuclear accident. A high prevalence of chromosomal
      rearrangements involving the RET gene was found among these radiation-induced
      thyroid tumors. As a result of such rearrangement, a portion of the RET gene is
      fused with another gene, typically with the H4 or ELE1 . However, since the DNA
      targets of ionizing radiation are randomly distributed throughout the cell
      nucleus, the reason for predilection for the RET rearrangements in thyroid cells
      was unclear.

PMID- 12805664
TI  - Signaling pathway puts the break on fat cell formation.
AB  - Obesity is approaching epidemic proportions in the western industrialized world,
      and is also becoming a major problem among young people in eastern and developing
      countries. Unfortunately, excess fat or adipose tissue is associated with a wide
      array of health problems, including increased incidence of type II diabetes,
      cardiovascular disease, hypertension, sleep apnea, and skeletomuscular problems.
      Obesity is the second leading cause of death from "unnecessary" causes in the
      U.S. (after smoking), and costs individuals and society billions of dollars
      worldwide to treat. Despite common wisdom that "one just needs to eat less and
      exercise more" and a multi-billion-dollar diet industry, epidemiological data
      indicate that the incidence of obesity will continue to rise. This alarming trend
      is, in part, due to the unprecedented availability of energy-dense foods and an
      increasingly sedentary lifestyle. These environmental factors may be complicated
      in some individuals by an unfavorable genetic predisposition. Pharmaceutical
      companies lead active research programs to identify drugs that target weight
      control centers in the body and which may help individuals control their weight;
      however, no satisfactory magic bullet to fight obesity has yet come through the
      pipeline.

PMID- 12805665
TI  - A bacterial toxin that causes DNA damage to modulate cellular responses.
AB  - Campylobacter jejuni constitutes the leading cause of bacterial diarrhea in the
      U.S. and all around the world. This common bacterium produces a toxin known as
      cytolethal distending toxin (CDT) which causes intoxicated cells to enlarge and
      to stop dividing with a double DNA content characteristic of G2/M arrest. The
      effect of the toxin on the cell is so striking that it captivated scientists for
      a long time. However, its mechanism of action had remained elusive.

PMID- 12805666
TI  - Identification of molecular substrate for the attenuation of anxiety: a step
      toward the development of better anti-anxiety drugs.
AB  - Anxiety disorders affect some 19 million people in the U.S. alone, costing $46.6
      billion, or one third of the nation's total mental health bill in 1990.
      Benzodiazepine tranquilizers like the prototypic diazepam are among the most
      widely used anti-anxiety agents. In addition to their anxiolytic action, they
      also induce sedation and may impair motor coordination, both of which are
      undesired side effects when they are used as anxiolytics. Not surprisingly, road
      traffic accidents may be increased for patients on classical benzodiazepines. In
      addition, these drugs carry the risk of dependence liability. Benzodiazepines
      augment the action of the inhibitory neurotransmitter g -aminobutyric acid (GABA)
      at contact points between two nerve cells called synapses, points at which
      information is transmitted from one nerve cell to the next. Synaptically released
      GABA binds to postsynaptic GABAA receptors, thus causing an influx of negatively
      charged chloride ions into the postsynaptic neuron. This leads to a
      hyperpolarization and thus functional inhibition of the postsynaptic cell.
      Benzodiazepines bind to a site on the GABA(A) receptor which is different from
      the GABA binding site, thus increasing the chloride current. Benzodiazepines like
      diazepam bind to GABA(A) receptors containing the alpha subunits alpha 1, alpha
      2, alpha 3, or alpha 5, most likely in alphabetagamma combinations.

PMID- 12805667
TI  - Bioreactors for decreasing the growth of brain tumors.
AB  - Malignant gliomas are the most common primary brain tumors. They are highly
      aggressive tumors characterized by a recurrence rate of virtually 100%. Despite
      significant advances in neuroimaging and neurosurgical techniques, the median
      survival time of patients with glioblastoma multiforme remains 12 to 18 months.
      Malignant gliomas are characterized by rapidly dividing cells, which invade into
      the normal brain, and a high degree of vascularity. Recent experimental evidence
      indicates that tumor-related angiogenesis contributes significantly to the
      malignant phenotype.

PMID- 12805668
TI  - Transgenic killer commensal bacteria as mucosal protectants.
AB  - As first line of defense against the majority of infections and primary site for
      their transmission, mucosal surfaces of the oral cavity and genitourinary,
      gastrointestinal, and respiratory tracts represent the most suitable sites to
      deliver protective agents for the prevention of infectious diseases. Mucosal
      protection is important not only for life threatening diseases but also for
      opportunistic infections which currently represent a serious burden in terms of
      morbidity, mortality, and cost of cures. Candida albicans is among the most
      prevalent causes of mucosal infections not only in immuno-compromised patients,
      such as HIV-infected subjects who are frequently affected by oral and esophageal
      candidiasis, but also in otherwise healthy individuals, as in the case of acute
      vaginitis. Unfortunately, current strategies for mucosal protection against
      candidiasis are severely limited by the lack of effective vaccines and the
      relative paucity and toxicity of commercially available antifungal drugs.

PMID- 12805669
TI  - Identification of a T1D susceptibility gene.
AB  - It is not known what causes type 1 diabetes (T1D) which affects over 1 million
      people in the U.S. alone. Each year, 30,000 young people in the U.S. develop this
      disease and depend on insulin injections thereafter. Because of the huge cost to
      the individual, the family, and to society in increased health care costs, it is
      important to find what makes these people susceptible. The disease process itself
      is clear: the individual's immune system, the T lymphocytes in particular, attack
      and destroy the body's insulin-producing cells. But how and why this autoimmune
      process starts or proceeds unregulated is still not known.

PMID- 12805670
TI  - Pesticides are involved with population declines of amphibians in the California
      Sierra Nevadas.
AB  - Several species of frogs and toads are in serious decline in the Sierra Nevada
      Mountains of California. These species include the threatened red-legged frog (
      Rana aurora ), foothill yellow-legged frog ( R. boylii ), mountain yellow-legged
      frog ( R. muscosa ), Cascades frog ( Rana cascadae ), western toad ( Bufo boreas
      ) and Yosemite toad ( B. canorus ). For many of these species current
      distributions are down to 10% of historical ranges. Several factors including
      introduced predators, habitat loss, and ultraviolet radiation have been suggested
      as causes of these declines. Another probable cause is air-borne pesticides from
      the Central Valley of California. The Central Valley, especially the San Joaquin
      Valley, is a major agricultural region where millions of pounds of active
      ingredient pesticides are applied each year
      (http://www.cdpr.ca.gov/dprdatabase.htm). Prevailing westerly winds from the
      Pacific Coast transport these pesticides into the into the Sierras.

PMID- 12805671
TI  - Some deafness-causing mutations can be silenced with the appropriate gene
      partner.
AB  - Inheritance of a deafness-causing genotype does not necessarily mean that a
      person will have profound hearing loss. The presence of a modifying gene can
      change the effect of the deafness genotype. As an example, mutations found
      commonly among the deaf are at times found among their normal hearing relatives.
      The implication is that there are genes or gene products whose interactions allow
      the normal physiological function of the inner ear despite a mutation that would
      normally disrupt the process. Deafness is not the first disorder in which
      modifiers can change the expected outcome, nor will it be the last, but it is
      very unusual for the outcome to be so dramatically changed.

PMID- 12805672
TI  - No pain, no gains.
AB  - No pain, no gains. Pain and memory are two critical functions of animals and
      humans. Through painful experience humans and animals learn what is potentially
      harmful and then store this information in the brain in order to avoid future
      injury. It is the essential skill for animals and humans to survive through their
      lifespan. However, it is unclear if both processes may share common signal
      molecules or proteins in the brain. It is known that the NMDA receptor, a
      receptor for glutamate, in the higher structures of the brain is important for
      memory formation and storage. NMDA receptors in the spinal cord contribute to
      central sensitization of sensory information such as pain after injuries.

PMID- 12805673
TI  - Pesticides and Parkinson's disease.
AB  - Parkinson's disease (PD), a common neurodegenerative disorder affects
      approximately 1% of the population over 65. PD is a late-onset progressive motor
      disease characterized by tremor, rigidity (stiffness), and bradykinesia (slowness
      of movement). The hallmark of PD is the selective death of dopamine-containing
      neurons in the substantia nigra pars compacta which send their projections to the
      striatum and the presence of cytoplasmic aggregates called Lewy bodies. Most
      cases of PD are sporadic but rare cases are familial, with earlier onset. The
      underlying mechanisms and causes of PD still remain unclear.

PMID- 12805674
TI  - The insulin-sensitive side of SHIP2.
AB  - A substantial and increasing proportion of death and disability in the EU (and
      elsewhere) is attributable to diseases associated with insulin resistance (i.e.,
      decreased insulin sensitivity). Beside type II diabetes, other diseases like
      obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian
      syndrome, and acromegaly are indeed associated with insulin resistance.

PMID- 12805675
TI  - Finding the stuff that dreams are made of.
AB  - The scientific study of dreams has had a long but tortured history. While the
      discovery of REM sleep in 1953 and its strong correlation with dreaming led to a
      renewed hope that the study of dreaming could be moved to a solidly scientific
      and physiological base, such studies have provided only mixed success. In 1977,
      Hobson and McCarley proposed the activation-synthesis model for dream
      construction based on the physiological features of REM sleep, but since then the
      field has shown surprisingly little progress.

PMID- 12805676
TI  - LTP in a culture dish.
AB  - The "aging" of populations in the developed world is rapidly altering
      demographics and presents a number of challenges for science and medicine.
      Foremost among these challenges is the need to enhance the quality of life for
      this "aging" majority. Paradoxically, improved prevention and treatment of
      diseases will only increase the number of individuals who will lose quality of
      life because of cognitive deficits in learning and memory. Such cognitive
      deficits are particularly vexing in societies where the ability to deal with
      information technology has become an increasing necessity. Understanding how the
      human brain encodes and stores information becomes critical in designing required
      therapeutic strategies.

PMID- 12805677
TI  - Lactococcus lactis, a tool for the delivery of therapeutic proteins treatment of
      IBD.
AB  - Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory
      diseases that consists of ulcerative colitis (UC), an inflammation of the large
      intestine, and Crohn's disease (CD), which can affect any part of the
      gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in
      western countries. There is a marked tendency in the age of onset toward
      gradually younger people. IBD represents a genuine problem in public health
      because of the absence of etiologic treatment. The clinical image is
      characterized by recurrent segmental or total inflammatory involvement of the
      large and/or small intestine, often resulting in a chronic, unpredictable course.
      The symptoms of both are extremely unpleasant and impact all aspects of quality
      of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea,
      weight loss, lethargy, and loss of appetite. If left untreated, malnutrition,
      dehydration, and anemia follow, which, in extreme cases, can even lead to death.
      Although many patients are managed successfully with conventional medical
      therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory
      to treatment, most will have recurrent activity of disease, and two thirds will
      require surgery. Administered orally or by injection, only a fraction of the
      active components of most conventional drugs reaches the intended target site,
      the inflamed intestinal lining. This is not only an inefficient way to deliver
      drugs, but, more important, means that patients are often subject to a spectrum
      of unpleasant side effects that result from the high levels of the drugs in
      other, otherwise healthy tissues and organs of the body.

PMID- 12805679
TI  - Lawmakers order EPA to clean up work environment.
AB  - Washington, Oct 6--On Wednesday, members of Congress ordered the Environmental
      Protection Agency (EPA) to do a "Superfund" cleanup of its own work environment.
      For 3 hours, lawmakers and the public listened as witnesses testified to patterns
      of intolerance, discrimination, and retaliation within the EPA--"This agency is
      run like a 21st century plantation and this has to stop," said witness and EPA
      policy analyst Marsha Coleman-Adebayo.

PMID- 12805680
TI  - Lawmakers demand answers from EPA.
AB  - Washington, Oct. 6--Early this afternoon, lawmakers demanded answers from
      Environmental Protection Agency (EPA) Administrator Carol Browner. In a letter
      sent earlier today to Browner, House Science Committee Chairman F. James
      Sensenbrenner, Jr. (R-WI) demanded to know why her testimony and that of one of
      her deputies, Ramulo Diaz, at Wednesday"s Science Committee hearing conflicted
      with actions taken yesterday by the agency.

PMID- 12805681
TI  - Modeling water resources: have we got it right?
AB  - Aquatic scientists generally recognize that controlled experiments are required
      to establish cause-effect relationships (e.g., Havens and Aumen, 2000), and
      understanding ecological processes is key to accurately predicting complex
      ecosystem responses. However, resource managers may have at their disposal only a
      limited amount of observational data when faced with management decisions. Hence,
      there may be a tendency to use simple empirical models for decision making. An
      example of eutrophication management in lakes illustrates a pitfall of this
      approach when used independently of other scientific information.

PMID- 12805682
TI  - Coral reefs: beyond mortality?
AB  - The scale of the collapse of coral reef communities in 1998 following a warming
      episode (Wilkinson, 2000) was unprecedented, and took many people by surprise.
      The Indian Ocean was the worst affected with a coral mortality over 75% in many
      areas such as the Chagos Archipelago (Sheppard, 1999), Seychelles (Spencer et
      al., 2000) and Maldives (McClanahan, 2000). Several other locations were affected
      at least as much, with mortality reaching 100% (to the nearest whole number);
      this is being compiled by various authors (e.g., CORDIO, in press). For example,
      in the Arabian Gulf, coral mortality is almost total across many large areas of
      shallow water (Sheppard, unpublished; D. George and D. John, personal
      communication). The mortality is patchy of course, depending on currents,
      location inside or outside lagoons, etc., but it is now possible to swim for over
      200 m and see not one remaining living coral or soft coral on some previously
      rich reefs.

PMID- 12805683
TI  - Whither acid rain?
AB  - Acid rain, the environmental cause celebre of the 1980s seems to have vanished
      from popular conscience. By contrast, scientific research, despite funding
      difficulties, has continued to produce hundreds of research papers each year.
      Studies of acid rain taught much about precipitation chemistry, the behaviour of
      snow packs, long-range transport of pollutants and new issues in the biology of
      fish and forested ecosystems. There is now evidence of a shift away from research
      in precipitation and sulfur chemistry, but an impressive theoretical base remains
      as a legacy.

PMID- 12805684
TI  - Water water everywhere.
AB  - During the last decade of the 20th century the world was exposed to increasing
      episodes of extreme weather. Figures reveal a 0.6 degrees C rise in average
      temperatures since records began in 1860, with the 1990s being the warmest decade
      and 1998 the warmest year. Experts believe that these rising temperatures, or
      global warming, are in part due to human influences.

PMID- 12805685
TI  - African biochemists plan more collaboration.

PMID- 12805686
TI  - The importance of peer reviewing.

PMID- 12805687
TI  - First derivative UV spectra of surface water as a monitor of chlorination in
      drinking water treatment.
AB  - Many countries require the presence of free chlorine at about 0.1 mg/l in their
      drinking water supplies. For various reasons, such as cast-iron pipes or long
      residence times in the distribution system, free chlorine may decrease below
      detection limits. In such cases it is important to know whether or not the water
      was chlorinated or if nonchlorinated water entered the system by accident.
      Changes in UV spectra of natural organic matter in lakewater were used to assess
      qualitatively the degree of chlorination in the treatment to produce drinking
      water. The changes were more obvious in the first derivative spectra. In
      lakewater, the derivative spectra have a maximum at about 280 nm. This maximum
      shifts to longer wavelengths by up to 10 nm, decreases, and eventually disappears
      with an increasing dose of chlorine. The water treatment system was monitored by
      this technique for over 1 year and changes in the UV spectra of water samples
      were compared with experimental samples treated with known amounts of chlorine.
      The changes of the UV spectra with the concentration of added chlorine are
      presented. On several occasions, water, which received very little or no
      chlorination, may have entered the drinking water system. The results show that
      first derivative spectra are potentially a tool to determine, in the absence of
      residual chlorine, whether or not surface water was chlorinated during the
      treatment to produce potable water.

PMID- 12805691
TI  - Hurricane effects on a shallow lake ecosystem and its response to a controlled
      manipulation of water level.
AB  - In order to reverse the damage to aquatic plant communities caused by multiple
      years of high water levels in Lake Okeechobee, Florida (U.S.), the Governing
      Board of the South Florida Water Management District (SFWMD) authorized a
      "managed recession" to substantially lower the surface elevation of the lake in
      spring 2000. The operation was intended to achieve lower water levels for at
      least 8 weeks during the summer growing season, and was predicted to result in a
      large-scale recovery of submerged vascular plants. We treated this operation as a
      whole ecosystem experiment, and assessed ecological responses using data from an
      existing network of water quality and submerged plant monitoring sites. As a
      result of large-scale discharges of water from the lake, coupled with losses to
      evaporation and to water supply deliveries to agriculture and other regional
      users, the lake surface elevation receded by approximately 1 m between April and
      June. Water depths in shoreline areas that historically supported submerged plant
      communities declined from near 1.5 m to below 0.5 m. Low water levels persisted
      for the entire summer. Despite shallow depths, the initial response (in June
      2000) of submerged plants was very limited and water remained highly turbid (due
      at first to abiotic seston and later to phytoplankton blooms). Turbidity
      decreased in July and the biomass of plants increased. However, submerged plant
      biomass did not exceed levels observed during summer 1999 (when water depths were
      greater) until August. Furthermore, a vascular plant-dominated assemblage
      (Vallisneria, Potamogeton, and Hydrilla) that occurred in 1999 was replaced with
      a community of nearly 98% Chara spp. (a macro-alga) in 2000. Hence, the lake"s
      submerged plant community appeared to revert to an earlier successional stage
      despite what appeared to be better conditions for growth. To explain this
      unexpected response, we evaluated the impacts that Hurricane Irene may have had
      on the lake in the previous autumn. In mid-October 1999, this category 1
      hurricane passed just to the south of the lake, with wind velocities over the
      lake surface reaching 90 km h(-1) at their peak. Output from a three-dimensional
      hydrodynamic/sediment transport model indicates that during the storm, current
      velocities in surface waters of the lake increased from near 5 cm s(-1) to as
      high as 100 cm s(-1). These strong velocities were associated with large-scale
      uplifting and horizontal transport of fine- grained sediments from the lake
      bottom. Water quality data collected after the storm confirmed that the hurricane
      resulted in lake-wide nutrient and suspended solids concentrations far in excess
      of those previously documented for a 10-year data set. These conditions persisted
      through the winter months and may have negatively impacted plants that remained
      in the lake at the end of the 1999 growing season. The results demonstrate that
      in shallow lakes, unpredictable external forces, such as hurricanes, can play a
      major role in ecosystem dynamics. In regions where these events are common (e.g.,
      the tropics and subtropics), consideration should be given to how they might
      affect long-term lake management programs.

PMID- 12805692
TI  - Toward a consistent pattern of ecosystem theories.
AB  - Several ecosystem theories have been presented during the last 2-3 decades.
      Lately it has been possible to unite these theories into a consistent pattern.
      Intensive discussions at meetings have been the key to the formation of this
      pattern of ecosystem theories. Another driving factor has been the reformulation
      of E.P. Odum's attributes into three growth forms: growth of the physical
      structure (the biomass), growth of the network (more cycling, more linkages), and
      growth of information. An analysis of the growth forms shows that through-flow
      (power), ascendancy, and exergy storage are all increasing as a consequence of
      all three types of growth. However, exergy dissipation, entropy production,
      specific exergy (exergy/biomass), retention time, and the ratio indirect/direct
      effect only increases or decreases with one or two of the growth forms.

PMID- 12805693
TI  - Harmful freshwater algal blooms, with an emphasis on cyanobacteria.
AB  - Suspended algae, or phytoplankton, are the prime source of organic matter
      supporting food webs in freshwater ecosystems. Phytoplankton productivity is
      reliant on adequate nutrient supplies; however, increasing rates of nutrient
      supply, much of it manmade, fuels accelerating primary production or
      eutrophication. An obvious and problematic symptom of eutrophication is rapid
      growth and accumulations of phytoplankton, leading to discoloration of affected
      waters. These events are termed blooms. Blooms are a prime agent of water quality
      deterioration, including foul odors and tastes, deoxygenation of bottom waters
      (hypoxia and anoxia), toxicity, fish kills, and food web alterations. Toxins
      produced by blooms can adversely affect animal (including human) health in waters
      used for recreational and drinking purposes. Numerous freshwater genera within
      the diverse phyla comprising the phytoplankton are capable of forming blooms;
      however, the blue-green algae (or cyanobacteria) are the most notorious bloom
      formers. This is especially true for harmful toxic, surface-dwelling, scum
      forming genera (e.g., Anabaena, Aphanizomenon, Nodularia, Microcystis) and some
      subsurface bloom-formers (Cylindrospermopsis, Oscillatoria) that are adept at
      exploiting nutrient-enriched conditions. They thrive in highly productive waters
      by being able to rapidly migrate between radiance-rich surface waters and
      nutrient-rich bottom waters. Furthermore, many harmful species are tolerant of
      extreme environmental conditions, including very high light levels, high
      temperatures, various degrees of desiccation, and periodic nutrient deprivation.
      Some of the most noxious cyanobacterial bloom genera (e.g., Anabaena,
      Aphanizomenon, Cylindrospermopsis, Nodularia) are capable of fixing atmospheric
      nitrogen (N2), enabling them to periodically dominate under nitrogen-limited
      conditions. Cyanobacteria produce a range of organic compounds, including those
      that are toxic to higher-ranked consumers, from zooplankton to further up the
      food chain. Both N2- and non-N2-fixing genera participate in mutualistic and
      symbiotic associations with microorganisms, higher plants, and animals. These
      associations appear to be of great benefit to their survival and periodic
      dominance. In this review, we address the ecological impacts and environmental
      controls of harmful blooms, with an emphasis on the ecology, physiology, and
      management of cyanobacterial bloom taxa. Combinations of physical, chemical, and
      biotic features of natural waters function in a synergistic fashion to determine
      the sensitivity of water bodies. In waters susceptible to blooms, human
      activities in water- and airsheds have been linked to the extent and magnitudes
      of blooms. Control and management of cyanobacterial and other phytoplankton
      blooms invariably includes nutrient input constraints, most often focused on
      nitrogen (N) and/or phosphorus (P). The types and amount of nutrient input
      constraints depend on hydrologic, climatic, geographic, and geologic factors,
      which interact with anthropogenic and natural nutrient input regimes. While
      single nutrient input constraints may be effective in some water bodies, dual N
      and P input reductions are usually required for effective long-term control and
      management of harmful blooms. In some systems where hydrologic manipulations
      (i.e., plentiful water supplies) are possible, reducing the water residence time
      by enhanced flushing and artificial mixing (in conjunction with nutrient input
      constraints) can be particularly effective alternatives. Implications of various
      management strategies, based on combined ecophysiological and environmental
      considerations, are discussed.

PMID- 12805694
TI  - Delineating novel signature patterns of altered gene expression in schizophrenia
      using gene microarrays.

PMID- 12805696
TI  - Complex analyses of plankton structure and function.
AB  - This paper critically evaluates some complex methods that have been used to
      characterize the structure and function of freshwater plankton communities. The
      focus is on methods related to plankton size structure and carbon transfer. The
      specific methods reviewed are 1) size spectrum analysis, 2) size-fractionated
      phytoplankton productivity, 3) size-fractionated zooplankton grazing, 4) plankton
      ecological transfer efficiency, and 5) grazer effects on phytoplankton community
      structure. Taken together, these methods can provide information on community
      ecological properties that are directly related to practical issues including
      water quality and fisheries productivity. However, caution is warranted since
      application without a complete understanding of assumptions and context of the
      manipulations could lead to erroneous conclusions. As an example, experimental
      studies involving the addition or removal of zooplankton, especially when coupled
      with nutrient addition treatments, could provide information on the degree of
      consumer vs. resource control of phytoplankton. Resource managers subsequently
      could use this information in developing effective measures for controlling
      nuisance algal biomass. However, the experiments must be done critically and with
      sufficient safeguards and other measurements to ensure that treatments (e.g.,
      zooplankton exclosure by screening of water) actually are successful and do not
      introduce other changes in the community (e.g., removal of large algae). In all
      of the methods described here, the investigator must take care when generalizing
      results and, in particular, carry out a sufficient number of replications to
      encompass both the major seasonal and spatial variation that occurs in the
      ecosystem.

PMID- 12805697
TI  - Why homeodynamics, not homeostasis?
AB  - Ideas of homeostasis derive from the concept of the organism as an open system.
      These ideas can be traced back to Heraclitus. Hopkins, Bernard, Hill, Cannon,
      Weiner and von Bertalanffy developed further the mechanistic basis of turnover of
      biological components, and Schoenheimer and Rittenberg were pioneers of
      experimental approaches to the problems of measuring pool sizes and dynamic
      fluxes. From the second half of the twentieth century, a biophysical theory
      mainly founded on self-organisation and Dynamic Systems Theory allowed us to
      approach the quantitative and qualitative analysis of the organised complexity
      that characterises living systems. This combination of theoretical framework and
      more refined experimental techniques revealed that feedback control of steady
      states is a mode of operation that, although providing stability, is only one of
      many modes and may be the exception rather than the rule. The concept of
      homeodynamics that we introduce here offers a radically new and all-embracing
      concept that departs from the classical homeostatic idea that emphasises the
      stability of the internal milieu toward perturbation. Indeed, biological systems
      are homeodynamic because of their ability to dynamically self-organise at
      bifurcation points of their behaviour where they lose stability. Consequently,
      they exhibit diverse behaviour; in addition to monotonic stationary states,
      living systems display complex behaviour with all its emergent characteristics,
      i.e., bistable switches, thresholds, waves, gradients, mutual entrainment, and
      periodic as well as chaotic behaviour, as evidenced in cellular phenomena such as
      dynamic (supra)molecular organisation and flux coordination. These processes may
      proceed on different spatial scales, as well as across time scales, from the very
      rapid processes within and between molecules in membranes to the slow time scales
      of evolutionary change. It is dynamic organisation under homeodynamic conditions
      that make possible the organised complexity of life.

PMID- 12805699
TI  - Surface level ozone and its adverse effects on crops and forests: a need for an
      interdisciplinary understanding.

PMID- 12805700
TI  - Cytochromes P450, oxygen, and evolution.
AB  - The role of the cytochrome P450 superfamily of heme-thiolate enzymes in oxidative
      metabolism is discussed in the context of evolutionary development. Concordances
      between the rise in atmospheric oxygen content, elaboration of the P450
      phylogenetic tree and the accepted timescale for the emergence of animal phyla
      are described. The unique ability of the P450 monooxygenase system to activate
      molecular oxygen via the consecutive input of two reducing equivalents is
      explored, such that the possibility of oxygen radical generation and its toxic
      consequences can be explained in mechanistic terms, together with an appreciation
      of the ways in which this oxygen activating ability has been utilized by evolving
      biological systems in their adaptation to an increasing atmospheric oxygen
      concentration over the past two billon years.

PMID- 12805714
TI  - Occurrence and antibiotic resistance of mesophilic Aeromonas in three riverine
      freshwaters of Marrakech, Morocco.
AB  - In order to evaluate the impact of pollution and sewage on the occurrence and
      antibiotic resistance of mesophilic aeromonads in riverine freshwaters of
      Marrakech, samples were collected from three rivers (Oukaimeden, Ourika, and
      Tensift) upstream and downstream from the principal bordering villages. During a
      2-year study, indicators of pollution increased dramatically in the downstream
      waters. Bacterial indicators (faecal coliforms and faecal streptococci)
      correlated with mesophilic aeromonads only in heavily polluted waters. In low and
      moderately polluted sources, densities of mesophilic aeromonads were independent
      of water quality indicators and did not correlate statistically with faecal
      indicators. Average counts of Aeromonas in low and heavily polluted waters were
      2.5 x 10(3) and 2.1 x 10(6) colony forming units per 100 ml, respectively. The
      biochemical identification of 841 isolates indicated a predominance of A. caviae
      in heavily and moderately polluted water and sediment. A. hydrophila was dominant
      only in low polluted waters and when the temperature was below 12 degrees C. High
      densities of A. sobria were found in low, moderately polluted, or cleaned waters
      and when the water temperature was above 18 degrees C. All selected isolates
      (total = 841) were tested for antibiotic susceptibility against 21 antibiotics.
      Antibiotic resistance frequencies recorded were: ampicillin and amoxicillin,
      100%; novobiocin, 96%; cefalotin, 81%; colistin, 72%; sulfamethoxazole, 40%;
      cefamandole, 37%; polymyxin B, 23%; trimethoprim, 17%; erythromycin, 15%;
      streptomycin, 8%; amoxicillin-clavulanate, 5%. Resistance to cefotaxime,
      kanamycin, gentamycin, chloramphenicol, tetracycline, oxytetracycline, nalidixic
      acid, rifampicin, or trimethoprim-sulfameth-oxazole was found to be <5%.
      Antibiotic resistance rates did vary according to the source of a strain"s
      isolation, and high numbers of antibiotic resistant strains were recorded in
      polluted samples. Since no correlation between mesophilic aeromonads and
      conventional faecal pollution indicators was observed in low or moderately
      polluted waters, and since these freshwaters are used for domestic supply, we
      propose the use of mesophilic aeromonads as complementary water pollution
      indicators to ensure the safety of water.

PMID- 12805715
TI  - Suppression of tumor angiogenesis by nonsteroidal anti-inflammatory drugs: a new
      function for old drugs.

PMID- 12805716
TI  - Structure of influenza a virus promoter and its implications for viral RNA
      synthesis.

PMID- 12805717
TI  - Passive sampler for measurements of atmospheric nitric acid vapor (HNO3)
      concentrations.
AB  - Nitric acid (HNO3) vapor is an important nitrogenous air pollutant responsible
      for increasing saturation of forests with nitrogen and direct injury to plants.
      The USDA Forest Service and University of California researchers have developed a
      simple and inexpensive passive sampler for monitoring air concentrations of HNO3.
      Nitric acid is selectively absorbed on 47-mm Nylasorb nylon filters with no
      interference from particulate NO3-. Concentrations determined with the passive
      samplers closely corresponded with those measured with the co-located honeycomb
      annular denuder systems. The PVC protective caps of standardized dimensions
      protect nylon filters from rain and wind and allow for reliable measurements of
      ambient HNO3 concentrations. The described samplers have been successfully used
      in Sequoia National Park, the San Bernardino Mountains, and on Mammoth Mountain
      in California.

PMID- 12805718
TI  - Sampling ozone exposure of Canadian forests at different scales: some case
      studies.
AB  - The use of passive samplers in extensive monitoring, such as that used in
      national forest health monitoring plots, indicates that these devices are able to
      determine both spatial and temporal differences in ozone exposure of the plots.
      This allows for categorisation of the plots and the potential for cause-effect
      analysis of certain forest health responses. Forest exposure along a gradient of
      air pollution deposition demonstrates large variation in accumulated exposures.
      The efficacy of using passive samplers for in situ monitoring of forest canopy
      exposure was also demonstrated. The sampler data produced weak relationships with
      ozone values from the nearest "continuous" monitor, even though data from
      colocated samplers showed strong relationships. This spatial variation and the
      apparent effect of elevation on ozone exposure demonstrate the importance of
      topography and tree canopy characteristics in plant exposure on a regional scale.
      In addition, passive sampling may identify the effects of local pollutant gases,
      such as NO, which may scavenge ozone locally only to increase the production of
      this secondary pollutant downwind, as atmospheric reactions redress the
      equilibrium between concentrations of this precursor and those of the generated
      ozone. The use of passive samplers at the stand level is able to resolve vertical
      profiles within the stand and edge effects that are important in exposure of
      understorey and ground flora. Recent case studies using passive samplers to
      determine forest exposure to ozone indicate a great potential for the development
      of spatial models on a regional, landscape, and stand level scale.

PMID- 12805719
TI  - Application of the ESRI Geostatistical Analyst for determining the adequacy and
      sample size requirements of ozone distribution models in the Carpathian and
      Sierra Nevada Mountains.
AB  - Models of O3 distribution in two mountain ranges, the Carpathians in Central
      Europe and the Sierra Nevada in California were constructed using ArcGIS
      Geostatistical Analyst extension (ESRI, Redlands, CA) using kriging and cokriging
      methods. The adequacy of the spatially interpolated ozone (O3) concentrations and
      sample size requirements for ozone passive samplers was also examined. In case of
      the Carpathian Mountains, only a general surface of O3 distribution could be
      obtained, partially due to a weak correlation between O3 concentration and
      elevation, and partially due to small numbers of unevenly distributed sample
      sites. In the Sierra Nevada Mountains, the O3 monitoring network was much denser
      and more evenly distributed, and additional climatologic information was
      available. As a result the estimated surfaces were more precise and reliable than
      those created for the Carpathians. The final maps of O3 concentrations for Sierra
      Nevada were derived from cokriging algorithm based on two secondary variables-
      elevation and maximum temperature as well as the determined geographic trend.
      Evenly distributed and sufficient numbers of sample points are a key factor for
      model accuracy and reliability.

PMID- 12805720
TI  - Premalignant lesions in the kidney.
AB  - Renal cell carcinoma (RCC) is the most malignant urologic disease. Different
      lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia
      in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been
      described for a number of years as possible premalignant changes or precursor
      lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from
      other causes were analyzed, and dysplastic lesions were identified and defined in
      detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for
      classification. The criteria for a lesion to be defined as premalignant are (1)
      morphological similarity; (2) spatial association; (3) development of
      microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive
      carcinoma; (5) progression to invasive cancer; and (6) similar genetic
      alterations. RIN resembles the neoplastic cells of RCC. There is spatial
      association. Progression to invasive carcinoma is described in experimental
      cancer models, and in some human renal tumors. Similar molecular alterations are
      found in some putative premalignant changes. The treatment for RCC is radical or
      partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in
      patients treated by partial nephrectomy and may be the source of local
      recurrences. RIN seems to be a biologic precursor of some RCCs and warrants
      further investigation. Interpretation and reporting of these lesions would reveal
      important resources for the biological nature and clinical significance. The
      management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be
      answered.

PMID- 12805721
TI  - The current status of microscopical hair comparisons.
AB  - Although the microscopical comparison of human hairs has been accepted in courts
      of law for over a century, recent advances in DNA technology have called this
      type of forensic examination into question. In a number of cases, post-conviction
      DNA testing has exonerated defendants who were convicted in part on the results
      of microscopical hair comparisons. A federal judge has held a Daubert hearing on
      the microscopical comparison of human hairs and has concluded that this type of
      examination does not meet the criteria for admission of scientific evidence in
      federal courts. A review of the available scientific literature on microscopical
      hair comparisons (including studies conducted by the Royal Canadian Mounted
      Police and the Federal Bureau of Investigation) leads to three conclusions: (1)
      microscopical comparisons of human hairs can yield scientifically defensible
      conclusions that can contribute to criminal investigations and criminal
      prosecutions, (2) the reliability of microscopical hair comparisons is strongly
      affected by the training of the forensic hair examiner, (3) forensic hair
      examiners cannot offer estimates of the probability of a match of a questioned
      hair with a hair from a randomly selected person. In order for microscopical hair
      examinations to survive challenges under the U.S. Supreme Court's Daubert
      decision, hair microscopists must be better trained and undergo frequent
      proficiency testing. More research on the error rates of microscopical hair
      comparisons should be undertaken, and guidelines for the permissible
      interpretations of such comparisons should be established. Until these issues
      have been addressed and satisfactorily resolved, microscopical hair comparisons
      should be regarded by law enforcement agencies and courts of law as merely
      presumptive in nature, and all microscopical hair comparisons should be confirmed
      by nuclear DNA profiling or mitochondrial DNA sequencing.

PMID- 12805722
TI  - Nitrogen emission and deposition: the European perspective.
AB  - Europe has been successful in reducing the emissions of several nitrogenous
      pollutants over recent decades. This is reflected in concentrations and
      deposition rates that have decreased for several components. Emissions of
      nitrogen containing gases are estimated to have decreased in Europe by 10%, 21%,
      and 14% for NO, NOx, and NH3, respectively, between 1990 and 1998. The main
      reductions are the result of a decrease in industrial and agricultural activities
      in the east of Europe as a result of the economic situation, measures in the
      transport sector, industry and agricultural sector, with only a small part of the
      reduction due to specific measures designed to reduce emissions. The reduction is
      significant, but far from the end goal for large areas in Europe in relation to
      different environmental problems. The Gothenburg Protocol will lead to reductions
      of 50 and 12% in 2010 relative to 1990 for NOx and NH3, respectively. The N2O
      emissions are expected to grow between 1998 and 2010 by 9%. Further reductions
      are necessary to reach critical limits for ecosystem protection, air quality
      standards and climate change. Emissions of nitrogen compounds result from an
      overload of reactive nitrogen, which is produced by combustion processes, by
      synthesis of ammonia or by import from other areas as concentrated animal feeds.
      Although some improvements can be made by improving the efficiency of combustion
      processes and agricultural systems, measures to reduce emissions substantially
      need to be focused on decreasing the production or import of reactive N. Reactive
      N ceilings for regions based on critical limits for all N-related effects can
      help to focus such measures. An integrated approach might have advantages over
      the pollutant specific approach to combat nitrogen pollution. This could provide
      the future direction for European policy to reduce the impacts of excess
      nitrogen.

PMID- 12805723
TI  - Relationships between Kovats retention indices and molecular descriptors of 1-(2
      hydroxy)-3-arylpropane-1,3-diones.
AB  - Experimental and theoretical results for retention index of a set of 20 beta
      diketones are given. The quantitative structure-chromatographic retention
      relationships (QSRR) theory is employed and six molecular descriptors are chosen
      to compute the fitting polynomials. Multiple regression analysis yields
      satisfactory results when one resorts to several variables equations, instead of
      computing just one-variable formulae. Average absolute deviations from
      experimental results are rather low, which seems to point out the suitability of
      the present approach.

PMID- 12805724
TI  - Small pulmonary lesions--a challenge for thoracic surgery?
AB  - We analyzed the diagnosis, the potentially associated external and clinical
      features, and the surgical procedures of small pulmonary lesions, especially
      hamartomas (in relation to peripheral T1 lung carcinomas and lymphoid
      hyperplasia) in 103 patients who experienced enucleation or resection of
      pulmonary hamartomas between March 1, 1995 and December 31, 2000. The causes of
      surgical intervention, presurgical diagnoses, surgical procedures, location,
      size, and histological compartments were analyzed, as well as clinical features
      potentially associated with the tumors (alcohol, asbestos, smoking, and chronic
      lung diseases). Follow up of patients lasted for 5.5 years at maximum. For
      comparison, 36 patients with peripheral T1 lung carcinomas are included as well
      as 50 patients with lymphoid hyperplasia. The sex and age distribution of the
      patients with hamartomas was comparable to that of patients with lymphoid
      hyperplasia. About 75% of men and 55% of women were heavy smokers, with an
      average history of 30 and 17 pack years, respectively. In 84% of patients, the
      lesions were incidentally detected in chest radiographs, whereas 12% of patients
      underwent thoracic surgery suspicious for intrapulmonary metastases of known
      extrapulmonary malignancies. Enucleation was performed in 21%, and wedge
      resection in 77% of patients. At average, hamartomas were smaller than T1 lung
      carcinomas, but considerably larger in comparison to lymphoid hyperplasia. No
      recurrent tumors or additionally detected hamartomas were noted during the follow
      up, and both surgical procedures (enucleation or wedge resection) were identical
      in curative treatment. All patients with peripherally localized T1 tumors
      underwent lobectomy. The 3/5 year survival rate was calculated to 69/52%.
      Lymphoid hyperplasia is of clinical importance for the estimation of prognosis in
      patients with metastatic disease, as the number of radiologically suggestive
      metastatic nodules can often be significantly changed due to this entity.
      Pulmonary hamartomas are benign lesions that display certain clinical
      associations with malignant lung carcinomas in respect to external risk factors,
      and to lymphoid hyperplasia. Both surgical procedures (enucleation or wedge
      resection) can be performed, giving identical results in respect to treatment.

PMID- 12805726
TI  - Vitamin A prevents inner ear defects in mice with congenital homeobox gene
      deficiency.
AB  - For the past 75 years, vitamin A and its biologically active metabolites, the
      retinoids, have been the object of intense study in biology and medicine. A large
      body of evidence demonstrates that these nutrients are essential for normal
      development and survival of vertebrate embryos, including mammals. In fact, it
      has been known since the mid-1930s that vitamin A deficiency during pregnancy
      results in death of the fetus and congenital abnormalities. Similarly, excess
      dietary intake of vitamin A can also cause teratogenic responses. Among the main
      targets of both deficiency and excess retinoid-induced teratogenesis are the
      heart, limbs, craniofacial structures, central nervous system, and the inner ear.
      Specific malformations are induced in a stage- and dose-dependent manner. Thus,
      these studies indicate that precise levels and timing of action of vitamin A
      metabolites are required for normal patterning of embryonic structures. In
      addition, the discovery of the nuclear receptors for retinoic acid (RA) and other
      vitamin A derivatives provided a molecular basis to explain how distinct doses of
      these compounds elicit cell-specific responses via the direct transcriptional
      activation of a panel of target genes.

PMID- 12805727
TI  - Extracellular and intracellular regulation of calcium homeostasis.
AB  - An organism with an internal skeleton must accumulate calcium while maintaining
      body fluids at a well-regulated, constant calcium concentration. Neither calcium
      absorption nor excretion plays a significant regulatory role. Instead, isoionic
      calcium uptake and release by bone surfaces causes plasma calcium to be well
      regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response
      to hormonal signals, modulate the available bone surfaces so that plasma calcium
      can increase when more low-affinity bone calcium binding sites are made available
      and can decrease when more high-affinity binding sites are exposed. The
      intracellular free calcium concentration of body cells is also regulated, but
      because cells are bathed by fluids with vastly higher calcium concentration,
      their major regulatory mechanism is severe entry restriction. All cells have a
      calcium-sensing receptor that modulates cell function via its response to
      extracellular calcium. In duodenal cells, the apical calcium entry structure
      functions as both transporter and a vitamin D--responsive channel. The channel
      upregulates calcium entry, with intracellular transport mediated by the mobile,
      vitamin D-dependent buffer, calbindin D9K, which binds and transports more than
      90% of the transcellular calcium flux. Fixed intracellular calcium binding sites
      can, like the body's skeleton, take up and release calcium that has entered the
      cell, but the principal regulatory tool of the cell is restricted entry.

PMID- 12805728
TI  - J'accuse.

PMID- 12805730
TI  - Rumbles and grumbles from around the world.
AB  - A different kind of shake-up will hit the science establishment when the New Year
      dawns in earthquake-prone Japan, reports Nature in its lead story this week.
      Science kicks off self-referentially with a lead story about its decision to
      publish a paper on sequencing the human genome from Craig Venter of Celera
      Genomics.

PMID- 12805732
TI  - Optimizing nitrogen management in food and energy production and environmental
      protection: summary statement from the Second International Nitrogen Conference.
AB  - Human efforts to produce food and energy are changing the nitrogen (N) cycle of
      the Earth. Many of these changes are highly beneficial for humans, while others
      are detrimental to people and the environment. These changes transcend scientific
      disciplines, geographical boundaries, and political structures. They challenge
      the creative minds of natural and social scientists, economists, engineers,
      business leaders, and decision makers. The Second International Nitrogen
      Conference was designed to facilitate communications among all stakeholders in
      the "nitrogen community" of the world. The Conference participants" goal in the
      years and decades ahead is to encourage every country to make optimal choices
      about N management in food production and consumption, energy production and use,
      and environmental protection. Scientific findings and recommendations for
      decision makers that emerged from the Conference are presented.

PMID- 12805733
TI  - Limitations of improved nitrogen management to reduce nitrate leaching and
      increase use efficiency.
AB  - The primary mode of nitrogen (N) loss from tile-drained row-cropped land is
      generally nitrate-nitrogen (NO3-N) leaching. Although cropping, tillage, and N
      management practices can be altered to reduce the amount of leaching, there are
      limits as to how much can be done. Data are given to illustrate the potential
      reductions for individual practices such as rate, method, and timing of N
      applications. However, most effects are multiplicative and not additive; thus it
      is probably not realistic to hope to get overall reductions greater than 25 to
      30% with in-field practices alone. If this level of reduction is insufficient to
      meet water quality goals, additional off-site landscape modifications may be
      necessary.

PMID- 12805734
TI  - Nitrogen and sulphur relations in effecting yield and quality of cereals and
      oilseed crops.
AB  - Nitrogen and sulphur, both vital structural elements, are especially needed for
      the synthesis of proteins and oils. Investigations revealed the required
      application of sulphur is one half to one third the amount of nitrogen, and the
      ratio becomes narrower in mustard (Brassica juncea L.), followed by wheat and
      rice. The efficiency of an increased level of nitrogen required a proportionately
      higher amount of sulphur. A critical investigation on the effective utilization
      of applied vis-a-vis absorbed nitrogen in wheat and mustard envisaged
      accumulation of NO3-N in vegetative parts when sulphur remained proportionately
      low. Application of sulphur hastened the chemical reduction of absorbed NO3- for
      its effective utilization. The effect was more pronounced in mustard than in
      wheat. Easily available forms of sulphur, like ammonium sulphate and gypsum, as
      compared to pyrite or elemental sulphur, maintained adequate N to S ratio in
      rice, resulting in a reduction in the percent of unfilled grain, a major
      consideration in rice yield. A narrow N to S ratio, with both at higher levels,
      increased the oil content but raised the saponification value of the oil, a
      measure of free fatty acids. Whereas, a proportionately narrow N to S ratio at
      moderate dose resulted in adequately higher seed and oil yield with relatively
      low saponification value, associated with increased iodine value of the oil,
      indicating respectively low free fatty acids and higher proportion of unsaturated
      fatty acids, an index for better quality of the oil.

PMID- 12805735
TI  - The environmental consequences of altered nitrogen cycling resulting from
      industrial activity, agricultural production, and population growth in China.
AB  - Human activities exerted very little effect on nitrogen (N) cycling in China
      before 1949. Between 1949 and 1999, however, rapid economic development and
      population growth led to dramatic changes in anthropogenic reactive N, inputted
      recycling N, N flux on land, N2O emission, and NH3 volatilization. Consequently,
      these changes have had a tremendous impact on the environment in China. In the
      current study, we estimated the amount of atmospheric wet N deposition and N
      transportation into water bodies from the watersheds and major valleys in China.
      Additionally, we addressed issues on leaching and accumulation of NO3- in the
      farmland under different climate zones, land use, and cropping systems as well as
      the potential influence of NO3- on underground water in China.

PMID- 12805736
TI  - Estimation of leaf nitrogen content from spectral characteristics of rice canopy.
AB  - Ground-based remotely sensed reflectance spectra of hyperspectral resolution were
      monitored during the growing period of rice under various nitrogen application
      rates. It was found that reflectance spectrum of rice canopy changed in both
      wavelength and reflectance as the plants developed. Fifteen characteristic
      wavebands were identified from the apparent peaks and valleys of spectral
      reflectance curves, in accordance with the results of the first-order
      differentiation, measured over the growing season of rice. The bandwidths and
      center wavelengths of these characteristic wavebands were different among
      nitrogen treatments. The simplified features by connecting these 15
      characteristic wavelengths may be considered as spectral signatures of rice
      canopy, but spectral signatures varied with developmental age and nitrogen
      application rates. Among these characteristic wavebands, the changes of the
      wavelength in band 11 showed a positive linear relationship with application
      rates of nitrogen fertilizer, while it was a negative linear relationship in band
      5. Mean reflectance of wavelengths in bands 1, 2, 3, 5, 11, and 15 was
      significantly correlated with application rates. Reflectance of these six
      wavelengths changed nonlinearly after transplanting and could be used in
      combination to distinguish rice plants subjected to different nitrogen
      application rates. From the correlation analyses, there are a variety of
      correlation coefficients for spectral reflectance to leaf nitrogen content in the
      range of 350-2400 nm. Reflectance of most wavelengths exhibited an inverse
      correlation with leaf nitrogen content, with the largest negative value (r = 
      0.581) located at about 1376 nm. Changes in reflectance at 1376 nm to leaf
      nitrogen content during the growing period were closely related and were best
      fitted to a nonlinear function. This relationship may be used to estimate and to
      monitor nitrogen content of rice leaves during rice growth. Reflectance of red
      light minimum and near-infrared peak and leaf nitrogen content were correlated
      nonlinearly.

PMID- 12805737
TI  - Optimization of aquatic-terrestrial ecosystem in relation to soil nitrogen status
      for the cultivation of fish and aquatic food crops of the Indian subtropics.
AB  - A case study was undertaken during wet and postwet seasons to improve the
      perennial and alternate submerged saucer-shaped ponded lands (tal and semi-tal
      lands) in the coasts and northeastern plains of the Indian subtropics through
      pisciculture and cultivation of starch- and protein-rich aquatic food crops like
      water chestnut (Trapa bispinosa Roxb.) and makhana or fox nut (Euryale ferox
      Salisb.). The study revealed that the physico-chemical properties of soils (pH,
      organic C, organic matter, available N, P, and K) as well as quality of water
      (pH, EC, BOD, COD, CO3 +, HCO3-, NO3-N, SO4-S-, and Cl-), growing fish, makhana,
      and water chestnut was remarkably influenced by different moisture regimes and
      exhibited a significant improvement of soil health. The amount of organic C,
      available N, P, and K content were found significantly highest in the treatment
      where makhana was grown under alternate flooding and drying situation with a
      depth >2 m as compared to other treatments. Such enrichment of soil fertility,
      particularly in available N and P content, might be due to the accumulation of
      considerable amounts of biomass and fish excreta and their subsequent
      decomposition in situ in the soils. Therefore, the present study suggests that
      the N-enriched soil may effectively be utilized further for growing subsequent
      arable crops surroundings during summer season, which not only saves the amount
      of applied N fertilizer but also increases the apparent N efficiency with
      simultaneous increase in yield, and would benefit the farmers in this region.

PMID- 12805738
TI  - Alternate nitrogen amendments for organic fertilizers.
AB  - The use of compost or manure in agriculture as an organic source of nutrients is
      common in many tropical, developing countries like Nigeria. One of the drawbacks
      of such materials is their low nitrogen (N) content (=1% N). Farmers commonly use
      chemical N fertilizers such as urea, calcium ammonium nitrate (CAN), and NPK
      formulations to obtain better crop growth and yield. These chemical supplements
      may have a negative impact on the environment through nitrate leaching into
      water, leading to eutrophication of surface waters that can affect public health.
      Gliricidia sepium, a fast-growing, tropical, perennial hedge plant was tested as
      a source of N in organo-mineral fertilizer formulations. Average nutrient content
      of Gliricidia is 3.8% N, 0.32% P, 1.8% K, 0.8% Ca, and 0.2% Mg. Using a sand
      culture and Amaranthus caudatus as a test crop, it was shown that amending
      commercial composts with 30% Gliricidia prunings would benefit many small-scale
      farmers and control environmental pollution.

PMID- 12805739
TI  - Numerical analysis of the transport and fate of nitrate in the soil and nitrate
      leaching to drains.
AB  - In this study, the transport and fate of nitrate within the soil profile and
      nitrate leaching to drains were analyzed by comparing historic field data with
      the simulation results of the DRAINMOD model. The nitrogen version of DRAINMOD
      was used to simulate the performance of the nitrogen transport and transformation
      of the Hooibeekhoeve experiment, situated in the sandy region of the Kempen
      (Belgium) and conducted for a 30-year (1969-1998) period. In the analysis, a
      continuous cropping with maize was assumed. Comparisons between experimentally
      measured and simulated state variables indicate that the nitrate concentrations
      in the soil and nitrate leaching to drains are controlled by the fertilizer
      practice, the initial conditions, and the rainfall depth and distribution.
      Furthermore, the study reveals that the model used gives a fair description of
      the nitrogen dynamics in the soil and subsurface drainage at field scale. From
      the comparative analysis between experimental data and simulation results it can
      also be concluded that the model after calibration is a useful tool to optimize
      as a function of the combination "climate-crop-soil-bottom boundary condition"
      the nitrogen application strategy resulting in an acceptable level of nitrate
      leaching for the environment.

PMID- 12805740
TI  - Increasing N retention in Coastal Plain agricultural watersheds.
AB  - Historically, N availability has limited agricultural production as well as
      primary production in coastal waters. Prior to the middle of the last century, N
      available for grain production generally was limited to that supplied by previous
      legume crops, released from soil organic matter, or returned to the soil in
      animal wastes. The development of infrastructure to produce relatively low-cost
      inorganic N fertilizers eliminated the need to focus management of the entire
      agricultural system on increasing soil N availability. Increased N availability
      has contributed to dramatic increases in agricultural production but also has led
      to increased losses of both N and C from agricultural systems. N losses from
      cropland have been linked to increased algal production in the Chesapeake Bay,
      with N loss from cropland estimated to be the primary N input to the Bay from
      Coastal Plain regions of the watershed. The decade-long effort to reduce these
      losses has focused on reducing agricultural N use, but this strategy has yet to
      yield apparent reductions in N loadings to Coastal Plain tributaries. Although
      nitrate leaching losses are often attributed to inefficient use of N inputs, soil
      nitrate data indicate that both corn and soybeans can utilize nearly all
      available soil nitrate during periods of active growth. However, both crops tend
      to stop utilizing nitrate before mineralization has ceased, resulting in a late
      season buildup of root zone nitrate levels and significant leaching losses even
      when no N was applied. Reducing nitrate losses due to the inherent N inefficiency
      of summer annual grain crops will require the addition of winter annual crops to
      rotations or changes in weed management approaches that result in plant N uptake
      capacity being more closely matched to soil microbial N processes.

PMID- 12805741
TI  - An innovative approach for locating and evaluating subsurface pathways for
      nitrogen loss.
AB  - Fundamental watershed-scale processes governing chemical flux to neighboring
      ecosystems are so poorly understood that effective strategies for mitigating
      chemical contamination cannot be formulated. Characterization of
      evapotranspiration, surface runoff, plant uptake, subsurface preferential flow,
      behavior of the chemicals in neighboring ecosystems, and an understanding of how
      crop management practices influence these processes are needed. Adequate
      characterization of subsurface flow has been especially difficult because
      conventional sampling methods are ineffective for measuring preferential flow of
      water and solutes. A sampling strategy based on ground-penetrating radar (GPR)
      mapping of subsurface structures coupled with near real-time soil moisture data,
      surface topography, remotely sensed imagery, and a geographic information system
      (GIS) appears to offer a means of accurately identifying subsurface preferential
      flow pathways. Four small adjacent watersheds draining into a riparian wetland
      and first-order stream at the USDA-ARS Beltsville Agricultural Research Center,
      Beltsville, MD are being studied with this protocol. The spatial location of some
      preferential flow pathways for chemicals exiting these agricultural watersheds to
      the neighboring ecosystems have been identified. Confirmation of the pathways is
      via examination of patterns in yield monitor data and remote sensing imagery.

PMID- 12805742
TI  - Deposition of atmospheric nitrogen compounds in humid tropical Cuba.
AB  - Acid deposition, a direct effect of gaseous air pollutants, is causing widespread
      damage to terrestrial and aquatic ecosystems. Further, these pollutants are
      responsible for the corrosion of building materials and cultural objects, as well
      as having an impact on human health. In Cuba, main atmospheric deposition of
      nitrogen compounds varies from approximately 12.0 to 65.0 kg N ha(-1) year(-1) in
      rural areas. Ammonia and ammonium are the most important elements in Cuba's
      tropical conditions.

PMID- 12805743
TI  - Nitrogen deposition to and cycling in a deciduous forest.
AB  - The project described here seeks to answer questions regarding the role increased
      nitrogen (N) deposition is playing in enhanced carbon (C) sequestration in
      temperate mid-latitude forests, using detailed measurements from an AmeriFlux
      tower in southern Indiana (Morgan-Monroe State Forest, or MMSF). The measurements
      indicate an average atmosphere-surface N flux of approximately 6 mg-N m(-2) day(
      1) during the 2000 growing season, with approximately 40% coming from dry
      deposition of ammonia (NH3), nitric acid (HNO3), and particle-bound N. Wet
      deposition and throughfall measurements indicate significant canopy uptake of N
      (particularly NH4+) at the site, leading to a net canopy exchange (NCE) of -6 kg
      N ha(-1) for the growing season. These data are used in combination with data on
      the aboveground C:N ratio, litterfall flux, and soil net N mineralization rates
      to indicate the level of potential perturbation of C sequestration at this site.

PMID- 12805744
TI  - Nitrogen deposition in the greater Tehran metropolitan area.
AB  - An investigation of air pollution in the Tehran metropolitan area between 1992
      2000 indicated that there are significant amounts of nitrate ion (NO3-), over 30
      kg/ha/year, deposited as wet deposition, compared to 13 kg/ha/year in the Chitgar
      Parkland near the Tehran metropolitan area. The amount of NO3- in warm seasons is
      twofold that of cold seasons, and there was a significant difference between cold
      and warm seasons. Annual wet deposition of ammonia (NH3) was 10 kg/ha/year in the
      Chitgar Parkland.

PMID- 12805745
TI  - Characterization of wet and dry deposition in the downwind of industrial sources
      in a dry tropical area.
AB  - An atmospheric deposition study was conducted in the downwind of Shaktinagar
      Thermal Power Plant (STPP), Renusagar Thermal Power Plant (RTPP), and Anpara
      Thermal Power Plant (ATPP), at Singrauli region, Uttar Pradesh (UP), India to
      characterize dry and wet deposition in relation to different pollution loading.
      During the study period, dry and wet depositions and levels of gaseous pollutants
      (SO2 and NO2) were estimated across the sites. Dry deposition was collected on a
      monthly basis and wet deposition on an event basis. Depositions were analyzed for
      pH, nitrate (NO3-), ammonium (NH4+), and sulphate (SO4(2-)) contents. Dry
      deposition rate both collected as clearfall and throughfall varied between 0.15
      to 2.28 and 0.33 to 3.48 g m(-2) day(-1), respectively, at control and maximally
      polluted sites. The pH of dry deposition varied from 5.81 to 6.89 during winter
      and 6.09 to 7.02 during summer across the sites. During the rainy season, the
      mean pH of clear wet deposition varied from 6.56 to 7.04 and throughfall varied
      from 6.81 to 7.22. The concentrations of NO2 and SO2 pollutants were highest
      during the winter season. Mean SO2 concentrations varied from 18 to 75 g m(-3) at
      control and differently polluted sites during the winter season. The variation in
      NO2 concentrations did not show a pattern similar to that of SO2. The highest NO2
      concentration during the winter season was 50 g m(-3), observed near RTPP. NO2
      concentration did not show much variation among different sites, suggesting that
      the sources of NO2 emission are evenly distributed along the sites. The
      concentrations of NH4+, NO3-, and SO4(2-) ions in dry deposition were found to be
      higher in summer as compared to the winter season. In dry deposition (clearfall)
      the concentrations of NH4+, NO3-, and SO4(2-) varied from 0.13 to 1.0, 0.81 to
      1.95, and 0.82 to 3.27 mg l(-1), respectively, during winter. In wet deposition
      (clearfall), the above varied from 0.14 to 0.74, 0.81 to 1.82, and 0.67 to 2.70
      mg l(-1), respectively. The study clearly showed that both dry and wet
      depositions varied between the sites and season, suggesting significant impact of
      industrial activities in modifying the atmospheric input. The nonacidic
      deposition suggests that there is no threat of acidification of the receiving
      ecosystem at present.

PMID- 12805746
TI  - Nitrogen management in a maize-groundnut crop rotation of humid tropics: effect
      on N2O emission.
AB  - Development of appropriate land management techniques to attain sustainability
      and increase the N use efficiency of crops in the tropics has been gaining
      momentum. The nitrous oxides (N2Os) affect global climate change and its
      contribution from N and C management systems is of great significance. Thus, N
      transformations and N2O emission during maize-groundnut crop rotation managed
      with various N sources were studied. Accumulation of nitrate (NO3- ) and its
      disappearance happened immediately after addition of various N sources, showing
      liming effect. The mineral N retained for 2-4 weeks depending on the type and
      amount of N application. The chicken manure showed rapid nitrification in the
      first week after application during the fallow period, leading to a maximum N2O
      flux of 9889 g N2O-N m(-2) day(-1). The same plots showed a residual effect by
      emitting the highest N2O (4053 microg N2O-N m(-2) day(-1)) during maize
      cultivation supplied with a half-rate of N fertilizer. Application of N
      fertilizer only or in combination with crop residues exhibited either lowered
      fluxes or caused a sink during the groundnut and fallow periods due to small
      availability of substrates and/or low water-filled pore space (<40%). The annual
      N2O emission ranged from 1.41 to 3.94 kg N2O-N ha(-1); the highest was estimated
      from the chicken manure plus crop residues and half-rate of inorganic N-amended
      plots. Results indicates a greater influence of chicken manure on the N
      transformations and thereby N2O emission.

PMID- 12805747
TI  - Quantification, sources, and control of ammonia emissions in the Czech Republic.
AB  - The exact quantification of ammonia (NH3) emissions is the basic presumption for
      the fulfillment of obligations set by the CLRTAP (Convention on Long Range
      Transboundary Air Pollution) Protocol which was signed by the Czech Republic in
      1999. Most NH 3 emissions in the Czech Republic are produced during the breeding
      of cattle, pigs, and poultry; therefore, determinating emission factors for these
      kinds of animals by studying their total number, type of breeding, and subsequent
      disposal of manure is the solution to the problem of NH 3 emissions
      quantification. This paper summarizes the results of 4 years of research in this
      area, determining the emission factors and ways of decreasing emissions from the
      breeding of cattle, pigs, and poultry.

PMID- 12805748
TI  - The recovery of damaged pine forests in an area formerly polluted by nitrogen.
AB  - An area in Lithuania containing coniferous stands of Scots pine and Norway spruce
      that were dead or damaged due to nitrogen pollution by a nitrogen fertilizer
      plant (JV Achema) was found to have expanded between 1974 and 1989 to a distance
      of 20 to 25 km northeast of the plant in the direction of prevailing winds. Over
      the last 10 years, when nitrogen pollution by the plant had decreased, a clear
      process of recovery of the damaged ecosystems could be observed. The following
      features of this process as it occurred in damaged Scots pine stands are
      discussed: (1) refoliation (or decreased defoliation) of damaged trees, where a
      clear positive trend could be observed; (2) changes in the species composition
      and in the covering by ground vegetation, where small changes and indication of
      less-nitrophilous species coverage could be detected; and (3) chemical and
      acidity changes in Luvisols and Arenosols, where a significant decrease could be
      seen especially concerning nitrate concentrations.

PMID- 12805749
TI  - Nitrogen cycling in a Norway spruce plantation in Denmark--a SOILN model
      application including organic N uptake.
AB  - A dynamic carbon (C) and nitrogen (N) circulation model, SOILN, was applied and
      tested on 7 years of control data and 3 years of manipulation data from an
      experiment involving monthly N addition in a Norway spruce ( Picea abies, L.
      Karst) forest in Denmark. The model includes two pathways for N uptake: (1) as
      mineral N after mineralisation of organic N, or (2) directly from soil organic
      matter as amino acids proposed to mimic N uptake by mycorrhiza. The model was
      parameterised and applied to the data from the control plot both with and without
      the organic N uptake included. After calibration, the models performance was
      tested against data from the N-addition experiment by comparing model output with
      measurements. The model reproduced well the overall trends in C and N pools and
      the N concentrations in soil solutions in the top soil layers whereas
      discrepancies in soil-solution concentrations in the deeper soil layers are seen.
      In the control data, the needle-N concentration was well reproduced except for
      small underestimations in some years because of drought effects not included in
      the model. In the N-addition experiment, SOILN reproduces the observed changes;
      in particular, the changes in needle-N concentrations and the overall
      distribution within the ecosystem of the extra added 3.5 g N m(-2) year(-1)
      parallel the observations. When organic N uptake is included, the simulations
      indicate that in the control plot receiving c. 1.9 g N m(-2) year(-1), the
      organic N uptake in average supplies 35% of the total plant N uptake. By addition
      of an extra 35 kg N ha(-1) year(-1), the organic N uptake is reduced to 16% of
      the total N uptake. Generally, inclusion of the pathway for organic N uptake
      improves model performance compared with observations for both C and N. This is
      because mineral N uptake alone implies a larger mineralisation rate, leading to
      bigger concentrations of N in the soil and soil water, bigger N losses, and net
      loss of c. 100 kg C ha(-1) year(-1), thereby causing depletion of the organic
      soil layer.

PMID- 12805750
TI  - Nitrogen fertilizer factory effects on the amino acid and nitrogen content in the
      needles of Scots pine.
AB  - The aim of the research was to evaluate the content of amino acids in the needles
      of Pinus sylvestris growing in the area affected by a nitrogen fertilizer factory
      and to compare them with other parameters of needles, trees, and sites. Three
      young-age stands of Scots pine were selected at a distance of 0.5 km, 5 km, and
      17 km from the factory. Examination of the current-year needles in winter of the
      year 2000 revealed significant (p < 0.05) differences between the site at a 0.5
      km distance from the factory and the site at a 17-km distance from the factory-
      with the site closest to the factory showing the highest concentrations of
      protein (119%), total arginine (166%), total other amino acids (depending on
      amino acid, the effect ranged between 119 and 149%), free arginine (771%), other
      free amino acids (glutamic acid, threonine, serine, lysine--depending on amino
      acid, the effect ranged between 162 and 234%), also the longest needles, widest
      diameter, largest surface area, and heaviest dry weight (respectively, 133, 110,
      136, and 169%). The gradient of nitrogen concentration in the needles was
      assessed on the selected plots over the period of 1995-2000, with the highest
      concentration (depending on year, 119 to 153%) documented in the site located 0.5
      km from the factory. Significant correlations were determined between the total
      amino acid contents (r = 0.448 -0.939, p < 0.05), some free amino acid (arginine,
      aspartic acid, glutamic acid, lysine, threonine, and serine) contents (r = 0.418 
      0.975, p < 0.05), and air pollutant concentration at the sites, the distance
      between the sites and the factory, and characteristics of the needles. No
      correlation was found between free or total arginine content and defoliation or
      retention of the needles. In conclusion, it was revealed that elevated mean
      monthly concentration of ammonia (26 microg m(-3)) near the nitrogen fertilizer
      factory caused changes in nitrogen metabolism, especially increasing (nearly
      eight times) concentration of free arginine in the needles of Scots pine.

PMID- 12805751
TI  - The impact of long-term nitrogen addition on microbial community composition in
      three Hawaiian forest soils.
AB  - We evaluated the microbial communities in three Hawaiian forest soils along a
      natural fertility gradient and compared their distinct responses to long-term
      nitrogen (N) additions. The sites studied have the same elevation, climate, and
      dominant vegetation, but vary in age of development, and thus in soil nutrient
      availability and nutrient limitation to plant growth. Fertilized plots at each
      site have received 100 kg ha year(-1) N addition for at least 8 years. Soil
      parameters, water content, pH, and ammonium and nitrate availability differed by
      site, but not between control and N-addition treatments within a site at the time
      of sampling. Microbial biomass also varied by site, but was not affected by N
      addition. In contrast, microbial community composition (measured by phospholipid
      analysis) varied among sites and between control and N-addition plots within a
      site. These data suggest that microbial community composition responds to N
      addition even when plant net primary productivity is limited by nutrients other
      than N. This may have implications for the behavior of forests impacted by
      atmospheric N deposition that are considered to be "nitrogen saturated," yet
      still retain N in the soil.

PMID- 12805752
TI  - Computation and visualization of regional-scale forest disturbance and associated
      dissolved nitrogen export from Shenandoah National Park, Virginia.
AB  - Long-term watershed research conducted in Shenandoah National Park (SNP) in
      Virginia and elsewhere in the eastern U.S. indicates that annual export of
      dissolved nitrogen (N) from gaged forested watersheds to surface waters increases
      dramatically in response to vegetation disturbances. Dissolved N leakage is a
      common, well-documented response of small forested watersheds to logging in the
      larger region, while recent defoliation outbreaks of the gypsy moth ( Lymantria
      dispar) larva in the deciduous forests of SNP have been shown to generate similar
      biogeochemical responses. A recent modeling analysis further suggests that a
      parsimonious, empirical, unit N export response function (UNERF) model can
      explain large percentages of the temporal variation in annual N export from a
      group of small gaged forested watersheds in the years following disturbance. The
      empirical UNERF modeling approach is completely analogous to the unit hydrograph
      technique for describing storm runoff, with the model representing annual N
      export as a linear deterministic process both in space and in time. The purposes
      of this analysis are to (1) test the applicability of the UNERF model using
      quarterly streamwater nitrate data from a group of ungaged watersheds in SNP; (2)
      demonstrate a park-wide application of a regional UNERF model that references the
      geographic distributions of bedrock geology and the timing and extent of gypsy
      moth defoliation over the entire SNP area; and (3) visualize the temporal and
      spatial patterns in vegetation disturbance and annual dissolved N export through
      the use of computer animation software. During water year 1992, the year of peak
      defoliation, our modeling study suggests that park-wide export had transiently
      increased by 1700% from a baseline rate of about 0.1 kg/ha/year. SNP forests
      appear to be characteristic of other N-limited second-growth forests in the
      eastern U.S. that leak little N under undisturbed conditions, despite receiving
      relatively large inputs of N from atmospheric deposition sources. Vegetation
      disturbances can apparently cause major changes in N input-output balances with
      potentially important ramifications for low-order forest streams and downstream
      receiving waters.

PMID- 12805753
TI  - Influence of different organic waste materials on the transformation of nitrogen
      in soils.
AB  - Organic waste materials like crop residues, well-decomposed cow dung, composts,
      and other rural and urban wastes are considered highly useful resources in
      enhancing soil fertility and also in build-up of soil organic matter. Organic
      matter decomposition provides plant nutrients in soil, which in turn increases
      crop productivity. Availability of nutrients and nitrogen (N) and phosphorus from
      organic waste materials is dependent upon the nature of organic residues,
      climatic conditions, and soil moisture activity. Keeping these factors in view,
      the present investigation was undertaken to study the transformation of N from
      different organic waste materials in two contrasting soils from an eastern India,
      subtropical region. The results showed that the amounts of ammoniacal-N (NH4-N),
      nitrate-N (NO3-N), hydrolysable N (HL-N), and nonhydrolysable (NHL-N) were
      increased for up to 60 days of soil submergence and increased further with the
      increase (1% by weight of soil) of organic residue application. Considering the
      effect of various organic waste materials, it was found that the amounts of NH4
      N, NO3-N, HL-N, and NHL-N were higher with the application of groundnut hull as
      compared to wheat straw and potato skin, which may be due to relatively narrow
      carbon:N ratio of groundnut (22:43) than that of wheat straw (62:84) and potato
      skin (71:32); however, the results showed that the release of NH4-N, NO3-N, HL-N,
      and NHL-N was in the order of groundnut hull > wheat straw > potato skin.

PMID- 12805754
TI  - Using simulation and budget models to scale-up nitrogen leaching from field to
      region in Canada.
AB  - Efforts are underway at Agriculture and Agri-Food Canada (AAFC) to develop an
      integrated, nationally applicable, socioeconomic/biophysical modeling capability
      in order to predict the environmental impacts of policy and program scenarios.
      This paper outlines our Decision Support System (DSS), which integrates the
      IROWCN (Indicator of the Risk of Water Contamination by Nitrogen) index with the
      agricultural policy model CRAM (Canadian Regional Agricultural Model) and
      presents an outline of our methodology to provide independent assessments of the
      IROWCN results through the use of nitrogen (N) simulation models in select, data
      rich areas. Three field-level models--DSSAT, N_ABLE, and EPIC--were evaluated
      using local measured data. The results show that all three dynamic models can be
      used to simulate biomass, grain yield, and soil N dynamics at the field level;
      but the accuracy of the models differ, suggesting that models need to be
      calibrated using local measured data before they are used in Canada. Further
      simulation of IROWCN in a maize field using N_ABLE showed that soil-mineral N
      levels are highly affected by the amount of fertilizer N applied and the time of
      year, meaning that fertilizer and manure N applications and weather data are
      crucial for improving IROWCN. Methods of scaling-up simulated IROWCN from field
      level to soil-landscape polygons and CRAM regions are discussed.

PMID- 12805755
TI  - Habitat management: a tool to modify ecosystem impacts of nitrogen deposition?
AB  - Atmospheric nitrogen deposition has been shown to affect both the structure and
      the function of heathland ecosystems. Heathlands are semi-natural habitats and,
      as such, undergo regular management by mowing or burning. Different forms of
      management remove more or less nutrients from the system, so habitat management
      has the potential to mitigate some of the effects of atmospheric deposition. Data
      from a dynamic vegetation model and two field experiments are presented. The
      first involves nitrogen addition following different forms of habitat management.
      The second tests the use of habitat management to promote heathland recovery
      after a reduction in nitrogen deposition. Both modelling and experimental
      approaches suggest that plant and microbial response to nitrogen is affected by
      management. Shoot growth and rates of decomposition were lowest in plots managed
      using more intensive techniques, including mowing with litter removal and a high
      temperature burn. Field data also indicate that ecosystem recovery from prolonged
      elevated inputs of nitrogen may take many years, or even decades, even after the
      removal of plant and litter nitrogen stores which accompanies the more intensive
      forms of habitat management.

PMID- 12805756
TI  - Economy of fertilizer nitrogen through organic sources in rain-fed rice-legume
      cropping systems in West Bengal, India.
AB  - Field experiments were conducted at a farmers" plot adjacent to the Regional
      Research Station, red and laterite zone, Sub-center Sekhampur (Birbhum district)
      of West Bengal, India, situated 23 degrees 24' N latitude, 87 degrees 24' E
      longitude, to study the effect of different bio- and organic sources of nutrients
      instead of total fertilizer N in terms of crop productivity in the sequence and
      building up of soil fertility. During the wet seasons of 1997 and 1998, 12
      combinations of bio- and organic sources (crop residues, well decomposed cow
      dung, dhanicha as green manure) were substituted for 25-50% of N fertilizer
      applied on transplanted rice (Cv. IR 36). Subsequently, during the winters of
      1997-1998 and 1998-1999, leguminous pulse crops like lentil (Lens culinaris [L.]
      Medic.), gram ( Cicer arietinum L.) and lathyrus (Lathyrus sativus L.) were grown
      with and without inoculation of Rhizobium. Results revealed that the application
      of inorganic N in combination with organic sources exhibited a significant
      increase in rice yield (3.60-3.84 t ha(-1) ) compared to the yield from sole
      application of N (3.19-3.26 t ha(-1) ). The study showed that about 25% of total
      applied N was saved without significant yield reduction with simultaneous
      improvement of soil physical properties (pH, organic matter, available N, P, K,
      and CEC). Seed yield of pulses (lentil, gram, and lathyrus) were more pronounced
      in the treatment inoculated with Rhizobium, with a saving of 42.6-48.4 kg N ha(
      1). Therefore, the results suggest that the combined application of inorganic and
      organic N sources in a 75:25 ratio is a superior N-management practice with
      regards to crop yields as well as improvement of soil fertility.

PMID- 12805757
TI  - Managing N inputs and the effect on N losses following excretion in open-dirt
      feedlots in Nebraska.
AB  - Nutrition will play an important role in meeting the environmental challenges of
      beef cattle feedlots. Nutritionists are continually refining protein
      requirements, and have recently adopted a new metabolizable protein (MP) system
      to more efficiently use nitrogen (N) and allow more accurate diet formulation.
      Protein requirements vary by animal age and weight during the finishing period.
      Our hypothesis was that formulating diets with the MP system would decrease N
      inputs and lead to decreased excretion and losses. Comparing industry average
      diets (13.5% crude protein) to phase-fed diets formulated to not exceed MP
      requirements decreased N inputs by 10 to 20% for calves and yearlings without
      affecting average daily gain. Decreasing inputs led to a concomitant decrease in
      N excretion (12 to 21%) and losses (15 to 33%) in open-dirt feedlot pens. N
      losses are variable with time of year, with averages of 60 to 70% of excreted N
      lost during the summer months and 40% lost during the November to May feeding
      periods. Protein requirements are being refined continually as more research data
      are collected. However, formulation to meet protein requirements, but not exceed
      them, is an important nutritional management option for feedlots to become
      sustainable.

PMID- 12805758
TI  - The EU Nitrates Directive: a European approach to combat water pollution from
      agriculture.
AB  - From 1991 onward, the European Union (EU) member states have had to comply with
      the Nitrates Directive. The aim of this directive is to sustainably protect
      ground and surface waters from pollution with nitrogen (nitrate) originating from
      agriculture. Agriculture is, on an EU level, the largest single source of nitrate
      (runoff, leaching) pollution, although households and industries also contribute
      to some extent. An important element in the directive is the reporting every 4
      years on the monitoring of ground- and surface-water quality. Furthermore, all 15
      member states are compelled to designate so-called Nitrate Vulnerable Zones
      (NVZs). These are regions where the nitrate concentrations in the groundwater
      amount to 50 mg/l or more. In addition to Codes of Good Agricultural Practice,
      valid on a countrywide basis and often consisting of voluntary-based measures,
      specific Action Programmes with mandatory measures have to be developed for the
      NVZs. The first reporting period ended in 1995. This paper describes the progress
      in member states" compliance with the Nitrates Directive during the second period
      (1996-1999), with a focus on the agricultural practices and action programmes. An
      evaluation of the member states' reports shows that good progress is being made
      on the farmers" awareness of the need to comply with EU regulations on the
      protection of the aquatic environment. Action programmes are valuable tools to
      enforce measures that lead to a reduction of the water pollution by agricultural
      activities. Regional projects show that significant improvements can be achieved
      (e.g., reduced fertiliser inputs) while maintaining crop yields and thus
      maintaining the economic potential of agriculture.

PMID- 12805759
TI  - Derivation and mapping of critical loads for nitrogen and trends in their
      exceedance in Germany.
AB  - The term "critical load" means a quantitative estimate of an exposure to one or
      more pollutants below which significant harmful effects on specified sensitive
      elements of the environment do not occur, according to present knowledge. In the
      case of nitrogen, both oxidised and reduced compounds contribute to the total
      deposition of acidity, which exceeds critical loads in many forest ecosystems.
      These also cause negative effects through eutrophication. Critical loads of
      nitrogen were derived for forest soils (deciduous and coniferous forest), natural
      grassland, acid fens, heathland, and mesotrophic peat bogs. In Germany, a
      decrease in sulphur emissions over the past 15 years resulted in a reduced
      exceedance of critical loads for acid deposition. In the same period it was noted
      that reduction in the emissions of nitrogen oxides and ammonia remained
      insignificant. Therefore, emissions of nitrogen compounds have become relatively
      more important and will continue to threaten ecosystem function and stability.
      The risk of environmental damage remains at an unacceptable level. The German
      maps show the degree to which the critical loads are exceeded, and they present
      current developments and an expected future trend. Results indicate that recovery
      from pollutant stress occurs only gradually.

PMID- 12805760
TI  - An enhanced rate-based emission trading program for NOX: the Dutch model.
AB  - Since 1997 government and industry in The Netherlands have been engaged in
      intensive policy discussions on how to design an emission trading program that
      would satisfy the Government's policy objectives within the national and
      international regulatory framework and accommodate industry's need for a flexible
      and cost-effective approach. Early on in the discussion the most promising
      solution was a rate-based approach, which dynamically allocated saleable emission
      credits based on a performance standard rate and actual energy used by
      facilities. All industrial facilities above a threshold of 20 MWth would be
      judged on their ability to meet this performance rate. Those "cleaner" than the
      standard can sell excess credits to others with an allocation that is less than
      their actual NOX emission. With some changes in law, such a design could be made
      to fit well into the national and EU legislative framework while at the same time
      uniquely meeting industry's requirement of flexibility toward economic growth and
      facility expansion. (An analysis of the legislative changes required will be
      given in a separate paper by Chris Dekkers.) However, the environmental outcome
      of such a system is not as certain as under an absolute emission cap. At the
      request of the Netherlands Ministry of Housing, Spatial Planning and the
      Environment (VROM), Automated Credit Exchange (ACE), in close cooperation with
      the working group of government and industry representatives introduced a number
      of features into the Dutch NOX program allowing full exploitation of market
      mechanisms while allowing intermediate adjustments in the performance standard
      rates. The design is geared toward meeting environmental targets without
      jeopardizing the trading market the program intends to create. The paper
      discusses the genesis of the two-tier credit system ACE helped to design,
      explains the differences between primary (fixed) and secondary (variable)
      credits, and outlines how the Dutch system is expected to function once
      implemented in 2004. The paper also discusses the market trading simulation held
      in early 2001 to assess and test the trading program, and reviews also the
      current status of the market program development.

PMID- 12805761
TI  - eNd points. Challenges for science and policy.

PMID- 12805763
TI  - Global biomonitoring of perfluorinated organics.
AB  - The environmental distribution of fluorinated organic compounds (FOCs) has been
      less well described than the other halogenated hydrocarbons such as chlorinated
      and brominated compounds. This is despite the fact that FOCs have been used in a
      wide variety of products and applications for more than 50 years. FOCs are
      resistant to hydrolysis, photolysis, microbial degradation, or metabolism by
      vertebrates due to the high energy of carbon-fluorine bond. In particular,
      perfluorinated (fully fluorinated) compounds (PFCs) have the potential to persist
      in the environment. But, until recently, the extent and magnitude of
      environmental distribution of PFCs was unknown. Recent development of an
      analytical technique for PFCs using high performance liquid chromatography
      negative ion electrospray tandem mass spectrometry (HPLC-ESMSMS) permitted the
      survey of PFCs in livers and blood plasma of wildlife on a global scale.

PMID- 12805764
TI  - Drugs from the sea: a marine sponge-derived compound prevents Type 1 diabetes.
AB  - More than one million Americans have Type 1 diabetes. This disease--also known as
      autoimmune or juvenile diabetes--strikes children suddenly, makes them dependent
      on insulin injections for life, and carries the constant threat of devastating
      complications. While it can and does strike adults, nearly half of all new cases
      are diagnosed in children. A child is diagnosed with Type 1 diabetes every hour.
      Type 1 diabetes is caused by the inability of a person"s pancreas to produce
      sufficient amounts of insulin to control their blood sugar levels and sustain
      life. While insulin injections allow affected individuals to control their blood
      sugar and stay alive, it is not a cure nor does it prevent the devastating
      complications of this disease, which include kidney failure, blindness,
      amputations, heart attack, and stroke. In Type 1 diabetes, the body"s own immune
      system goes awry, attacking and destroying insulin-producing cells in the
      pancreas.

PMID- 12805765
TI  - Breaking immunological tolerance through OX40 (CD134).
AB  - Immunological tolerance represents a mechanism by which cells of the host remain
      protected from the immune system. Breaking of immunological tolerance can result
      in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and
      multiple sclerosis. The reasons for tolerance breaking down and autoimmune
      processes arising are largely unknown but of obvious interest for therapeutic
      intervention of these diseases. Although reversal of the tolerant state is
      generally unwanted, there are instances where this may be of benefit to the host.
      In particular, one way a cancerous cell escapes being targeted by the immune
      system is through tolerance mechanisms that in effect turn off the reactivity of
      T lymphocytes that can respond to tumor-associated peptides. Thus tolerance
      represents a major obstacle in developing effective immunotherapy against tumors.
      The molecules that are involved in regulating immunological tolerance are then of
      interest as they may be great targets for positively or negatively manipulating
      the tolerance process.

PMID- 12805766
TI  - Plant functions in wetland and aquatic systems: influence of intensity and
      capacity of soil reduction.
AB  - Wetland or hydric soils, in addition to excess water and limited air-filled
      porosity, are characterized by anaerobic or reducing conditions. Wetland plants
      have developed physiological and morphological adaptations for growing under
      these conditions. Various methods exist for measuring plant responses to reducing
      conditions in wetland and aquatic environments, including assessment of radial
      oxygen transport, cellular enzymatic transformations, changes in root structure,
      and nutrient uptake. However, a gap exists in quantifying the chemical properties
      and reducing nature of soil environment in which plant roots are grown. The
      variation in reducing conditions, oxygen demand, and other associated processes
      that occur in wetland soils makes it difficult to truly compare the plant
      responses reported in the literature. This review emphasizes soil-plant
      interactions in wetlands, drawing attention to the importance of quantifying the
      intensity and capacity of reduction and/or oxygen demand in wetland soils to
      allow proper evaluation of wetland plant responses to such conditions.

PMID- 12805767
TI  - Gene silencing and antigenic variation in malaria parasites.
AB  - Malaria remains one of the most important infectious diseases in the world today,
      infecting 300 to 500 million people yearly and resulting in 1 to 2 million
      deaths, primarily of young African children. The most severe form of this disease
      is caused by infection with the mosquito borne protozoan parasite Plasmodium
      falciparum. This parasite lives by invading and multiplying within the red blood
      cells of its host, causing disease through anemia resulting from red cell
      destruction, and also through modifications made to the surface of infected red
      cells. These modifications make infected cells cytoadherent or "sticky", allowing
      them to adhere to the walls of blood vessels, leading to obstruction of blood
      flow and such clinical manifestations as the often fatal syndrome of cerebral
      malaria. In addition, parasites are capable of undergoing antigenic variation, a
      process of continually changing the identity of proteins on the surface of
      infected cells and thus avoiding the immune response mounted by the host. This
      process promotes a long term, persistent infection that is difficult to clear.

PMID- 12805768
TI  - Symbiotic gene activation is interrupted by endocrine disrupting chemicals.
AB  - Endocrine disrupting chemicals (EDCs) include organochlorine pesticides, plastics
      manufacturing by-products, and certain herbicides. These chemicals have been
      shown to disrupt hormonal signaling in exposed wildlife, lab animals, and
      mammalian cell culture by binding to estrogen receptors (ER-+/- and ER-) and
      affecting the expression of estrogen responsive genes. Additionally, certain
      plant chemicals, termed phytoestrogens, are also able to bind to estrogen
      receptors and modulate gene expression, and as such also may be considered EDCs.
      One example of phytoestrogen action is genistein, a phytochemical produced by
      soybeans, binding estrogen receptors, and changing expression of estrogen
      responsive genes which certain studies have linked to a lower incidence of
      hormonally related cancers in Japanese populations. Why would plants make
      compounds that are able to act as estrogens in the human body? Obviously,
      soybeans do not intentionally produce phytoestrogens to prevent breast cancer in
      Japanese women.

PMID- 12805769
TI  - From litterfall to breakdown in streams: a review.
AB  - This paper is a review of recent (< or =10 years) information on litterfall,
      standing stock of benthic organic matter, breakdown rates, and fungal
      colonization of organic matter in streams. In some cases, recent research
      reinforces the findings of classic reference papers. In other cases, the
      additional knowledge provided by recent research introduces a higher variation in
      the processes analyzed. In many aspects, especially those concerning stream
      organic matter, the review is biased towards the temperate North American
      streams, reflecting the fact that most research was carried out there. However,
      during the 1990s European studies increased enormously, especially those related
      with instream processes, such as leaf litter decomposition. The first part of
      this review analyzes the origin of allochthonous organic matter to streams
      (litterfall, retention, and storage), and it provides data on the amounts
      estimated in different streams and on the methodology used in the studies. The
      second part analyzes the fate of detritus in streams: mechanisms of leaf
      breakdown, relative importance of fungi and bacteria, factors affecting the
      activity of microbial decomposers, and chemical changes of leaf litter during
      decomposition. A list of breakdown rates of several different leaf species is
      given, together with the methodology used, and the main characteristics of the
      incubation streams.

PMID- 12805770
TI  - Sex-change chemicals and their influence on the brain.
AB  - The potential for man-made chemicals to mimic or antagonise natural hormones is a
      controversial issue, but one for which increasing amounts of evidence are being
      gathered worldwide. The controversy surrounds not so much the matter of whether
      these chemicals can mimic hormones in vitro--this phenomenon has been widely
      accepted in the scientific world - but more whether, as a result, they can
      disrupt reproduction in a wildlife situation. It has, nevertheless, been
      acknowledged that many wildlife populations are exhibiting reproductive and/or
      developmental abnormalities such as intersex gonads in wild roach populations in
      the U.K. and various reproductive disorders in alligators in Lake Apopka,
      Florida. However, the causative agents for many of these effects are difficult to
      specify, due to the extensive mixtures of chemicals--each of which may act via
      different pathways--to which wild populations are exposed, together with the wide
      variability observed even in natural (uncontaminated) habitats. As a result, any
      information detailing fundamental mechanism of action of the so-called endocrine
      disrupting chemicals (EDCs) is of use in determining whether or not these
      chemicals, as they are present in the environment, may in fact be capable of
      causing some of the effects observed in wildlife over recent years.

PMID- 12805771
TI  - Ensuring the stability of the genome: DNA damage checkpoints.
AB  - The cellular response to DNA damage is vital for the cell"s ability to maintain
      genomic integrity. Checkpoint signalling pathways, which induce a cell cycle
      arrest in response to DNA damage, are an essential component of this process.
      This is reflected by the functional conservation of these pathways in all
      eukaryotes from yeast to mammalian cells. This review will examine the cellular
      response to DNA damage throughout the cell cycle. A key component of the DNA
      damage response is checkpoint signalling, which monitors the state of the genome
      prior to DNA replication (G1/S) and chromosome segregation (G2/M). Checkpoint
      signalling in model systems including mice, Xenopus laevis, Drosophila
      melanogaster, and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces
      pombe have been useful in elucidating these pathways in mammalian cells. An
      examination of this research, with emphasis on the function of checkpoint
      proteins, their relationship to DNA repair, and their involvement in oncogenesis
      is undertaken here.

PMID- 12805772
TI  - Integrating individual-based indices of contaminant effects. How multiple
      sublethal effects may ultimately reduce amphibian recruitment from a contaminated
      breeding site.
AB  - Habitat contamination can alter numerous biological processes in individual
      organisms. Examining multiple individual-level responses in an integrative
      fashion is necessary to understand how individual health or fitness reflects
      environmental contamination. Here we provide an example of such an integrated
      perspective based upon recent studies of an amphibian (the bullfrog, Rana
      catesbeiana ) that experiences several, disparate changes when larval development
      occurs in a trace element-contaminated habitat. First, we present an overview of
      studies focused on specific responses of individuals collected from, or
      transplanted into, a habitat contaminated by coal combustion residues (CCR).
      These studies have reported morphological, behavioral, and physiological
      modifications to individuals chronically interacting with sediments in the CCR
      contaminated site. Morphological abnormalities in the oral and tail regions in
      contaminant-exposed individuals influenced other properties such as grazing,
      growth, and swimming performance. Behavioral changes in swimming activities and
      responses to stimuli appear to influence predation risk in the contaminant
      exposed population. Significant changes in bioenergetics in the contaminated
      habitat, evident as abnormally high energetic expenditures for survival
      (maintenance) costs, may ultimately influence production pathways (growth, energy
      storage) in individuals. We then present a conceptual model to examine how
      interactions among the affected systems (morphological, behavioral,
      physiological) may ultimately bring about more severe effects than would be
      predicted if the responses were considered in isolation. A complex interplay
      among simultaneously occurring biological changes emerges in which multiple,
      sublethal effects ultimately can translate into reductions in larval or juvenile
      survival, and thus reduced recruitment of juveniles into the population. In
      systems where individuals are exposed to low concentrations of contaminants for
      long periods of time, research focused on one or few sublethal responses could
      substantially underestimate overall effects on individuals. We suggest that
      investigators adopt a more integrated perspective on contaminant-induced
      biological changes so that studies of individual-based effects can be better
      integrated into analyses of mechanisms of population change.

PMID- 12805773
TI  - Anti-inflammatory activity of compounds isolated from plants.
AB  - This review shows over 300 compounds isolated and identified from plants that
      previously demonstrated anti-inflammatory activity. They have been classified in
      appropriate chemical groups and data are reported on their pharmacological
      effects, mechanisms of action, and other properties.

PMID- 12805774
TI  - Spatial and annual temporal distribution of ozone concentrations in the madrid
      basin using passive samplers.
AB  - Passive samplers are useful tools for helping to describe the ozone distribution
      in complex terrain situations. They are also a good complement to continuous
      monitoring stations. This paper discusses the results of a pilot study that used
      ozone passive samplers to describe the spatial and annual temporal distribution
      of ozone in several forested areas around the city of Madrid. The ozone
      concentrations around Madrid were found to be higher on the elevated sites
      located at a certain distance from the city"s urban zone. A seasonal ozone cycle
      was observed, with maximum concentrations found in the basin in late spring or
      summer depending on the location. The information obtained allowed us to group
      the locations into four classes. Altitude and distance to the city during the
      summer and winter explained the observed ozone concentrations. However, during
      the transition periods, especially in early spring and to a lesser extent in
      autumn, there was not a good correlation between ozone levels and elevation or
      distance from precursor sources. These data strongly suggest that altitudinal
      gradients for ozone are not always the case in the Madrid Basin.

PMID- 12805778
TI  - Symbiotic performance of herbaceous legumes in tropical cover cropping systems.
AB  - Increasing use of herbaceous legumes such as mucuna ( Mucuna pruriens var. utilis
      [Wright] Bruck) and lablab ( Lablab purpureus [L.] Sweet) in the derived savannas
      of West Africa can be attributed to their potential to fix atmospheric nitrogen
      (N2). The effects of management practices on N2 fixation in mucuna and lablab
      were examined using 15N isotope dilution technique. Dry matter yield of both
      legumes at 12 weeks was two to five times more in in situ mulch (IM) than live
      mulch (LM) systems. Land Equivalent Ratios, however, showed 8 to 30% more
      efficient utilization of resources required for biomass production under LM than
      IM systems. Live mulching reduced nodule numbers in the legumes by one third
      compared to values in the IM systems. Similarly, nodule mass was reduced by 34 to
      58% under LM compared to the IM systems. The proportion of fixed N2 in the
      legumes was 18% higher in LM than IM systems. Except for inoculated mucuna, the
      amounts of N fixed by both legumes were greater in IM than LM systems. Rhizobia
      inoculation of the legumes did not significantly increase N2 fixation compared to
      uninoculated plots. Application of N fertilizer reduced N2 fixed in the legumes
      by 36 to 51% compared to inoculated or uninoculated systems. The implications of
      cover cropping, N fertilization, and rhizobia inoculation on N contributions of
      legumes into tropical low-input systems were discussed.

PMID- 12805779
TI  - Nitrogen balance of effluent irrigated silage cropping systems in southern
      Australia.
AB  - The nitrogen (N) balance in a double-cropped, effluent spray irrigation system
      was examined for several years in southern Australia. The amounts of N added by
      irrigation, removed in the crop, and lost by ammonia (NH3) volatilisation,
      denitrification, and leaching were measured. Results from the project provide pig
      producers with the knowledge necessary to evaluate the efficiency of such systems
      for managing N, and enable sustainable effluent reuse practices to be developed.
      Oats were grown through the winter (May to November) without irrigation, and
      irrigated maize was grown during the summer/autumn (December to April).
      Approximately 18 mm of effluent was applied every 3 days. The effluent was
      alkaline (pH 8.3) and the average ammoniacal-N (NH4+ + NH3) concentration was 430
      mg N/l (range: 320 to 679 mg N/l). Mineral N in the 0- to 1.7-m layer tended to
      increase during the irrigation season and decrease during the winter/spring.
      About 2000 kg N/ha was found in the profile to a depth of 2 m in October 2000. N
      removed in the aboveground biomass (oats + maize) was 590 and 570 kg N/ha/year,
      equivalent to 25% of the applied N. Average NH3 volatilisation during the daytime
      (6:00 to 19:00) was 2.74 kg N/ha, while volatilisation at night (19:00 to 6:00)
      was 0.4 kg N/ha, giving a total of 3.1 kg N/ha/day. This represents approximately
      12% of the N loading, assuming that these rates apply throughout the season. The
      balance of the N accumulated in the soil profile during the irrigation season, as
      15N-labelled N studies confirmed. The high recovery of the 15N-labelled N, and
      the comparable distribution of 15N and Br in the soil profile, implied that there
      was little loss of N by denitrification, even though the soil was wet enough for
      leaching of both tracers.

PMID- 12805780
TI  - Improving nitrogen efficiency: lessons from Malawi and Michigan.
AB  - Two case studies are presented here of nitrogen (N) dynamics in potato/maize
      systems. Contrasting systems were investigated from (1) the highland tropics of
      Dedza, Malawi in southern Africa and (2) the northern temperate Great Lakes
      region of Michigan. Formal surveys were conducted to document grower perceptions
      and N management strategies. Survey data were linked with N budgets conducted by
      reviewing on-farm data from representative farms in the targeted agroecosystems
      and simulation modeling to estimate N losses. Potential N-loss junctures were
      identified. Interventions that farmers might accept are discussed. The Malawi
      system uses targeted application of very small amounts of fertilizer (average 18
      kg N ha(-1)) to growing plants. This low rate is on the steep part of plant
      response to N curve and should serve to enhance efficiency; plant growth,
      however, is generally stunted in Malawi due to degraded soils and weed
      competition. Very limited crop yields reduce N efficiency from a simulated 60 kg
      grain per kg N to an actual of approximately 20 kg grain per kg N (at 40 kg N ha(
      1) applied). Legume-intensified systems could improve growth potential and
      restore N use efficiency through amelioration of soil quality and transfer
      functions and from biological fixation N inputs. In the Michigan system, N
      efficiency is enhanced currently through multiple, split applications of N
      fertilizer tailored to plant growth rate and demand. Fertilizer N rates used by
      growers, however, averaged 32% higher than recommended rates and 40% higher than
      N removed in crop product. Application of 50 kg N ha(-1) to cover crops in the
      fall may contribute to the apparent high potential for N leaching losses. Careful
      consideration of N credits from legumes and residual soil N would improve N
      efficiency. Overall, N budgets indicated 0 to 20 kg N ha(-1) loss potential from
      the Malawi systems and tenfold higher loss potential from current practice in
      Michigan maize/potato rotations. Best management practices, with or without
      integration of legumes, could potentially reduce N losses in Michigan to a more
      acceptable level of about 40 kg N ha(-1).

PMID- 12805781
TI  - Soil nitrate monitoring for turfgrass sod farms and other turf areas.
AB  - Studies with established turf and golf courses have indicated minimal risk of
      nitrate pollution of groundwater resulting from turfgrass management, but soil
      nitrate flux in turfgrass sod production farms and golf courses has received less
      attention. Information about nitrate-N flux at a particular location can be
      helpful to the sod producer or the golf course manager when efficiently applying
      N fertilizers and minimizing risk of nitrate pollution. We used an ion exchange
      resin capsule system to continuously monitor soil nitrate-N fluxes at 12 sites in
      southern Rhode Island, including turfgrass sod production farms and a low
      maintenance environment. Four capsules were placed in the soil at each site and
      retrieved at intervals coinciding with management and meteorological events to
      determine nitrate ion accumulation. We found that the golf course green exhibited
      significantly higher nitrate-N fluxes than the sod farms and the low-maintenance
      turf. There was significant interaction between sampling date and study site,
      indicating that seasonal variation in soil nitrate-N fluxes was affected by
      turfgrass management. The cultural practice of late fall fertilization to
      stimulate early spring growth in the following year appeared to present some risk
      of nitrate loss during the winter from the golf course greens in our region. We
      conclude that site-specific and time-relevant monitoring is needed to produce and
      manage turfgrasses in an environmentally sound manner.

PMID- 12805782
TI  - The role of nitrogen-efficient cultivars in sustainable agriculture.
AB  - To improve nitrogen (N) efficiency in agriculture, integrated N management
      strategies that take into consideration improved fertilizer, soil, and crop
      management practices are necessary. This paper reports results of field
      experiments in which maize (Zea mays L.) and oilseed rape (Brassica napus L.)
      cultivars were compared with respect to their agronomic N efficiency (yield at a
      given N supply), N uptake efficiency (N accumulation at a given N supply), and N
      utilization efficiency (dry matter yield per unit N taken up by the plant). Under
      conditions of high N supply, significant differences among maize cultivars were
      found in shoot N uptake, soil nitrate depletion during the growing season, and
      the related losses of nitrate through leaching after the growing season.
      Experiments under conditions of reduced N supply indicated a considerable
      genotypic variation in reproductive yield formation of both maize and oilseed
      rape. High agronomic efficiency was achieved by a combination of high uptake and
      utilization efficiency (maize), or exclusively by high uptake efficiency (rape).
      N-efficient cultivars of both crops were characterized by maintenance of a
      relatively high N-uptake activity during the reproductive growth phase. In rape
      this trait was linked with leaf area and photosynthetic activity of leaves. We
      conclude that growing of N-efficient cultivars may serve as an important element
      of integrated nutrient management strategies in both low- and high-input
      agriculture.

PMID- 12805783
TI  - Gliricidia (Gliricidia sepium) Green manures as a potential source of N for maize
      production in the tropics.
AB  - Use of cheap, N-rich, and environmentally benign legume green manures to correct
      N deficiency in infertile soils is a very attractive option in the humid tropics.
      Understanding the influence of management and climate on their effectiveness, and
      quantifying their contribution to crop productivity, is therefore crucial for
      technology adoption and adaptation. Mineral N buildup and the contribution to N
      uptake in maize were studied in an Ultisol amended with fresh Gliricidia leaves.
      Net mineral N accumulation was compared in mulched and incorporated treatments in
      a field incubation study. The 15 N isotope dilution technique was used to
      quantify N supplied to maize by Gliricidia leaves in an alley cropping. Mineral N
      accumulation was slow, but was much greater after incorporation than after
      mulching. Also, N buildup was always higher in the topsoil (0 to 10 cm) than in
      the subsoil (10 to 20 cm). More NO3-N was leached than NH4-N, and the effect was
      greater in the incorporated treatment. Surface-applied Gliricidia leaves
      significantly increased N uptake by maize, and supplied >30% of the total N in
      the stover and >20% of that in the corn grain, even in the presence of hedgerows.
      Thus Gliricidia leaf mulch has immense potential to improve productivity in
      tropical soils.

PMID- 12805784
TI  - Urea-triazone N characteristics and uses.
AB  - Urea-triazone nitrogen (N) is a stable solution resulting from a controlled
      reaction in aqueous medium of urea, formaldehyde, and ammonia which contains at
      least 25% total N. This N source contains no more than 40%, nor less than 5%, of
      total N from unreacted urea and not less that 40% from triazone. All other N
      shall be derived from water-soluble dissolved reaction products of the above
      reactants. It is a source of slowly available N. The rate of mineralization of
      urea-triazone is about 66% that of urea after 8 days when incorporated in a
      Munjor sandy loam. Ammonia volatilization losses of N applied as urea-triazone
      were about 41% of those from urea on a Cecil sandy loam in the first week after
      application. N leaching losses through saturated Yolo loam columns of urea
      triazone were about two thirds that of urea or nitrate N. This N source has
      proven to be a safer and more effective material for direct application on plant
      foliage. Tomato growth was enhanced with foliar application of urea-triazone
      relative to that obtained from ammonium nitrate or urea. The stability of this N
      source from potential losses via ammonia volatilization and nitrate leaching when
      soil applied is also documented by results from university trials.

PMID- 12805785
TI  - Factors affecting microbial formation of nitrate-nitrogen in soil and their
      effects on fertilizer nitrogen use efficiency.
AB  - Mineralization of soil organic matter is governed by predictable factors with
      nitrate-N as the end product. Crop production interrupts the natural balance,
      accelerates mineralization of N, and elevates levels of nitrate-N in soil. Six
      factors determine nitrate-N levels in soils: soil clay content, bulk density,
      organic matter content, pH, temperature, and rainfall. Maximal rates of N
      mineralization require an optimal level of air-filled pore space. Optimal air
      filled pore space depends on soil clay content, soil organic matter content, soil
      bulk density, and rainfall. Pore space is partitioned into water- and air-filled
      space. A maximal rate of nitrate formation occurs at a pH of 6.7 and rather
      modest mineralization rates occur at pH 5.0 and 8.0. Predictions of the soil
      nitrate-N concentrations with a relative precision of 1 to 4 microg N g(-1) of
      soil were obtained with a computerized N fertilizer decision aid. Grain yields
      obtained using the N fertilizer decision aid were not measurably different from
      those using adjacent farmer practices, but N fertilizer use was reduced by >10%.
      Predicting mineralization in this manner allows optimal N applications to be
      determined for site-specific soil and weather conditions.

PMID- 12805786
TI  - Prediction of nitrogen responses of corn by soil nitrogen mineralization
      indicators.
AB  - Soil nitrogen mineralization potential (N min) has to be spatially quantified to
      enable farmers to vary N fertilizer rates, optimize crop yields, and minimize N
      transfer from soils to the environment. The study objectives were to assess the
      spatial variability in soil N min potential based on clay and organic matter (OM)
      contents and the impact of grouping soils using these criteria on corn grain (Zea
      mays L.) yield, N uptake response curves to N fertilizer, and soil residual N.
      Four indicators were used: OM content and three equations involving OM and clay
      content. The study was conducted on a 15-ha field near Montreal, Quebec, Canada.
      In the spring 2000, soil samples (n = 150) were collected on a 30- x 30-m grid
      and six rates of N fertilizer (0 to 250 kg N ha(-1)) were applied. Kriged maps of
      particle size showed areas of clay, clay loam, and fine sandy loam soils. The N
      min indicators were spatially structured but soil nitrate (NO3-) was not. The N
      fertilizer rate to reach maximum grain yield (N max), as estimated by a quadratic
      model, varied among textural classes and Nmin indicators, and ranged from 159 to
      250 kg N ha(-1). The proportion of variability (R2) and the standard error of the
      estimate (SE) varied among textural groups and N min indicators. The R2 ranged
      from 0.53 to 0.91 and the SE from 0.13 to 1.62. Corn grain N uptake was
      significantly affected by N fertilizer and the pattern of response differed with
      soil texture. For the 50 kg N ha(-1) rate, the apparent N min potential (ANM) was
      significantly larger in the clay loam (122 kg ha(-1)) than in the fine sandy loam
      (80 kg ha(-1)) or clay (64 kg ha(-1)) soils. The fall soil residual N was not
      affected by N fertlizer inputs. Textural classes can be used to predict N max.
      The N min indicators may also assist the variable rate N fertilizer inputs for
      corn production.

PMID- 12805787
TI  - Nitrogen efficiency in agriculture in Europe and India.
AB  - Nitrogen balance sheets are useful tools for studying the quantitative aspects of
      nutrients. Nitrogen balance sheets have been prepared for the animal production
      system, crop production system, and for the agricultural sector as a whole for
      all 15 member states of the European Union (EU15) and for the Indian
      subcontinent. The EU15 and India were chosen for this study on nitrogen
      efficiency using balance sheets because they each occupy roughly 300 million ha
      of land and use about 65 kg nitrogen fertiliser per hectare of agricultural land.
      Balance sheets were constructed for three systems: animal production, crop
      production, and the agricultural sector as a whole. In addition to detailed
      descriptions of the nitrogen balance sheets, brief recommendations for reducing
      nitrogen surpluses are also given. Surprisingly, the balance sheets for crop
      production and the agricultural sector as a whole showed a surplus of about 60 kg
      of nitrogen per hectare of agricultural land.

PMID- 12805788
TI  - Surface and subsurface nitrate flow pathways on a watershed scale.
AB  - Determining the interaction and impact of surface runoff and subsurface flow
      processes on the environment has been hindered by our inability to characterize
      subsurface soil structures on a watershed scale. Ground penetrating radar (GPR)
      data were collected and evaluated in determining subsurface hydrology at four
      small watersheds in Beltsville, MD. The watersheds have similar textures, organic
      matter contents, and yield distributions. Although the surface slope was greater
      on one of the watersheds, slope alone could not explain why it also had a nitrate
      runoff flux that was 18 times greater than the other three watersheds. Only with
      knowledge of the subsurface hydrology could the surface runoff differences be
      explained. The subsurface hydrology was developed by combining GPR and surface
      topography in a geographic information system. Discrete subsurface flow pathways
      were identified and confirmed with color infrared imagery, real-time soil
      moisture monitoring, and yield monitoring. The discrete subsurface flow patterns
      were also useful in understanding observed nitrate levels entering the riparian
      wetland and first order stream. This study demonstrated the impact that
      subsurface stratigraphy can have on water and nitrate (NO3-N) fluxes exiting
      agricultural lands, even when soil properties, yield distributions, and climate
      are similar. Reliable protocols for measuring subsurface fluxes of water and
      chemicals need to be developed.

PMID- 12805789
TI  - Partial validation of the Dutch model for emission and transport of nutrients
      (STONE).
AB  - The Netherlands has to cope with large losses of N and P to groundwater and
      surface water. Agriculture is the dominant source of these nutrients,
      particularly with reference to nutrient excretion due to intensive animal
      husbandry in combination with fertilizer use. The Dutch government has recently
      launched a stricter eutrophication abatement policy to comply with the EC nitrate
      directive. The Dutch consensus model for N and P emission to groundwater and
      surface water (STONE) has been developed to evaluate the environmental benefits
      of abatement plans. Due to the possibly severe socioeconomic consequences of
      eutrophication abatement plans, it is of utmost importance that the model is
      thoroughly validated. Because STONE is applied on a nationwide scale, the model
      validation has also been carried out on this scale. For this purpose the model
      outputs were compared with lumped results from monitoring networks in the upper
      groundwater and in surface waters. About 13,000 recent point source observations
      of nitrate in the upper groundwater were available, along with several hundreds
      of observations showing N and P in local surface water systems. Comparison of
      observations from the different spatial scales available showed the issue of
      scale to be important. Scale issues will be addressed in the next stages of the
      validation study.

PMID- 12805790
TI  - Modeling of nitrogen in river water using a detailed and a simplified model.
AB  - To model catchment surface water quantity and quality, different model types are
      available. They vary from detailed physically based models to simplified
      conceptual and empirical models. The most appropriate model type for a certain
      application depends on the project objectives and the data availability. The
      detailed models are very useful for short-term simulations of representative
      events. They cannot be used for long-term statistical information or as a
      management tool. For those purposes, more simplified (conceptual or meta-) models
      must be used. In this study, nitrogen dynamics are modeled in a river in
      Flanders. Nitrogen sources from agricultural leaching and domestic point sources
      are considered. Based on this input, concentrations of ammonium (NH4-N) and
      nitrate (NO3-N) in the river water are modeled in MIKE 11 by taking into
      consideration advection and dispersion and the most important biological and
      chemical processes. Model calibration was done on the basis of available measured
      water quality data. To this detailed model, a more simplified model was
      calibrated with the objective to more easily yield long-term simulation results
      that can be used in a statistical analysis. The results show that the conceptual
      simplified model is 1800 times faster than the MIKE 11 model. Moreover the two
      models have almost the same accuracy. The detailed models are recommended for
      short-term simulations unless there are enough data for model input and model
      parameters. The conceptual simplified model is recommended for long-term
      simulations.

PMID- 12805791
TI  - Distribution and sources of nitrate-nitrogen in Kansas groundwater.
AB  - Kansas is primarily an agricultural state. Irrigation water and fertilizer use
      data show long- term increasing trends. Similarly, nitrate-N concentrations in
      groundwater show long-term increases and exceed the drinking-water standard of 10
      mg/l in many areas. A statistical analysis of nitrate-N data collected for local
      and regional studies in Kansas from 1990 to 1998 (747 samples) found significant
      relationships between nitrate-N concentration with depth, age, and geographic
      location of wells. Sources of nitrate-N have been identified for 297 water
      samples by using nitrogen stable isotopes. Of these samples, 48% showed
      fertilizer sources (+2 to +8) and 34% showed either animal waste sources (+10 to
      +15 with nitrate-N greater than 10 mg/l) or indication that enrichment processes
      had occurred (+10 or above with variable nitrate-N) or both. Ultimate sources for
      nitrate include nonpoint sources associated with past farming and fertilization
      practices, and point sources such as animal feed lots, septic systems, and
      commercial fertilizer storage units. Detection of nitrate from various sources in
      aquifers of different depths in geographically varied areas of the state
      indicates that nonpoint and point sources currently impact and will continue to
      impact groundwater under current land uses.

PMID- 12805792
TI  - Organic nitrogen in precipitation: real problem or sampling artefact?
AB  - Published observations of organic nitrogen (N) compounds in precipitation go back
      almost a century. Several different methods have been used to measure both the
      total and ionic concentrations of N. There is therefore some uncertainty as to
      whether reported "organic N" is real, or simply the result of uncertainties in
      chemical analyses or inadequate sampling methods. We found that the materials
      from which the collector was made (polypropylene, steel, or glass) had no
      significant effect on the composition of dissolved organic N (DON). The use of a
      biocide was found to be very important during sampling and storage of samples
      before analysis. We set up a network of seven collectors across the U.K., from
      the Cairngorms to Dorset, all operating to the same protocol, and including a
      biocide. Samples were analysed centrally, using proven methods. Over 6 months,
      organic N contributed about 20% to the total N in U.K. precipitation, but with a
      large variation across the country. This means that current estimates of wet
      deposited N to the U.K., which are based only on the ammonium and nitrate
      concentrations, are too small. Organic N is not an artefact, but a real problem
      that needs to be addressed.

PMID- 12805793
TI  - A spatial analysis of atmospheric ammonia and ammonium in the U.K.
AB  - As measures are implemented internationally to reduce SO2 and NOx emissions,
      attention is falling on the contribution of NH3 emissions to acidification,
      nitrogen eutrophication, and aerosol formation. In the U.K., a monitoring network
      has been established to measure the spatial distribution and long-term trends in
      atmospheric gaseous NH3 and aerosol NH4+. At the same time, an atmospheric
      chemistry and transport model, FRAME, has been developed with a focus on reduced
      nitrogen (NHx). The monitoring data are important to evaluate the model, while
      the model is essential for a more detailed spatial assessment. The national
      network is established with over 80 sampling locations. Measurements of NH3 and
      NH4+ (at up to 50 sites) have been made using a new low-cost denuder-filterpack
      system. Additionally, improved passive sampling methods for NH3 have been applied
      to explore local variability. The measurements confirm the high spatial
      variability of NH3 (annual means 0.06 to 11 microg NH3 m(-3)), consistent with
      its nature as a primary pollutant emitted from ground-level sources, while NH4+,
      being a slowly formed secondary product, shows much less spatial variability
      (0.14 to 2.4 mg NH4+ m(-3)). These features are reproduced in the FRAME model,
      which provides estimates at a 5-km level. Analysis of the underlying NH3 emission
      inventory shows that sheep emissions may have been underestimated and
      nonagricultural sources overestimated relative to emissions from cattle. The
      combination of model and measurements is applied to estimate spatial patterns of
      dry deposition to different vegetation types. The combined approach provides the
      basis to assess NHx responses across the U.K. to international emission controls.

PMID- 12805794
TI  - Concentrations, deposition, and effects of nitrogenous pollutants in selected
      California ecosystems.
AB  - Atmospheric deposition of nitrogen (N) in California ecosystems is ecologically
      significant and highly variable, ranging from about 1 to 45 kg/ha/year. The
      lowest ambient concentrations and deposition values are found in the eastern and
      northern parts of the Sierra Nevada Mountains and the highest in parts of the San
      Bernardino and San Gabriel Mountains that are most exposed to the Los Angeles air
      pollution plume. In the Sierra Nevada Mountains, N is deposited mostly in
      precipitation, although dry deposition may also provide substantial amounts of N.
      On the western slopes of the Sierra Nevada, the majority of airborne N is in
      reduced forms as ammonia (NH3) and particulate ammonium (NH4+) from agricultural
      activities in the California Central Valley. In southern California, most of the
      N air pollution is in oxidized forms as nitrogen oxides (NOx), nitric acid
      (HNO3), and particulate nitrate (NO3-) resulting from fossil fuel combustion and
      subsequent complex photochemical reactions. In southern California, dry
      deposition of gases and particles provides most (up to 95%) of the atmospheric N
      to forests and other ecosystems. In the mixed-conifer forest zone, elevated
      deposition of N may initially benefit growth of vegetation, but chronic effects
      may be expressed as deterioration of forest health and sustainability. HNO3 vapor
      alone has a potential for toxic effects causing damage of foliar surfaces of
      pines and oaks. In addition, dry deposition of predominantly HNO3 has lead to
      changes in vegetation composition and contamination of ground- and stream water
      where terrestrial N loading is high. Long-term, complex interactions between N
      deposition and other environmental stresses such as elevated ozone (O3), drought,
      insect infestations, fire suppression, or intensive land management practices may
      affect water quality and sustainability of California forests and other
      ecosystems.

PMID- 12805795
TI  - Emissions of nitrous oxide and nitric oxide from soils of native and exotic
      ecosystems of the Amazon and Cerrado regions of Brazil.
AB  - This paper reviews reports of nitrous oxide (N2O) and nitric oxide (NO) emissions
      from soils of the Amazon and Cerrado regions of Brazil. N2O is a stable
      greenhouse gas in the troposphere and participates in ozone-destroying reactions
      in the stratosphere, whereas NO participates in tropospheric photochemical
      reactions that produce ozone. Tropical forests and savannas are important sources
      of atmospheric N2O and NO, but rapid land use change could be affecting these
      soil emissions of N oxide gases. The five published estimates for annual
      emissions of N2O from soils of mature Amazonian forests are remarkably
      consistent, ranging from 1.4 to 2.4 kg N ha(-1) year(-1), with a mean of 2.0 kg N
      ha(-1) year(-1). Estimates of annual emissions of NO from Amazonian forests are
      also remarkably similar, ranging from 1.4 to 1.7 kg N ha(-1) year(-1), with a
      mean of 1.5 kg N ha(-1) year(-1). Although a doubling or tripling of N2O has been
      observed in some young (< or = 2 years) cattle pastures relative to mature
      forests, most Amazonian pastures have lower emissions than the forests that they
      replace, indicating that forest-to-pasture conversion has, on balance, probably
      reduced regional emissions slightly (<10%). Secondary forests also have lower
      soil emissions than mature forests. The same patterns apply for NO emissions in
      Amazonia. At the only site in Cerrado where vegetation measurements have been
      made N2O emissions were below detection limits and NO emissions were modest
      (approximately 0.4 kg N ha(-1) year(-1)). Emissions of NO doubled after fire and
      increased by a factor of ten after wetting dry soil, but these pulses lasted only
      a few hours to days. As in Amazonian pastures, NO emissions appear to decline
      with pasture age. Detectable emissions of N2O have been measured in soybean and
      corn fields in the Cerrado region, but they are modest relative to fluxes
      measured in more humid tropical agricultural regions. No measurements of NO from
      agricultural soils in the Cerrado region have been made, but we speculate that
      they could be more important than N2O emissions in this relatively dry climate.
      While a consistent pattern is emerging from these studies in the Amazon region,
      far too few data exist for the Cerrado region to assess the impact of land use
      changes on N oxide emissions.

PMID- 12805796
TI  - Future trends in worldwide river nitrogen transport and related nitrous oxide
      emissions: a scenario analysis.
AB  - We analyze possible future trends in dissolved inorganic nitrogen (DIN) export by
      world rivers and associated emissions of nitrous oxide (N2O). Our scenarios
      either assume that current trends continue or that nitrogen (N) inputs to aquatic
      systems are reduced as a result of changes in agriculture practices and fuel
      combustion technologies. The results indicate that moderate changes in the human
      diet in North America and Europe, reducing worldwide fertilizer use by only 16%,
      relative to Business-as-Usual (BAU) levels, may reduce DIN export rates to the
      North Atlantic and European Seas by about one third and associated N2O emissions
      by 36 to 77%. We furthermore calculate that relatively large reductions in NOy
      deposition rates in Europe (of about 80%) may reduce DIN export by rivers by a
      moderate 8% or less, relative to BAU levels. The potential effect of reduced NOy
      deposition on riverine DIN export is moderate, because most N in European rivers
      stems from agriculture, and not from fuel combustion. Nevertheless, the
      calculated 9% reduction (relative to BAU) in DIN inputs to the North Sea as a
      potential side effect of air pollution control may help achieve the international
      policy targets for reduced N inputs to the North Sea.

PMID- 12805797
TI  - Developing seasonal ammonia emission estimates with an inverse modeling
      technique.
AB  - Significant uncertainty exists in magnitude and variability of ammonia (NH3)
      emissions, which are needed for air quality modeling of aerosols and deposition
      of nitrogen compounds. Approximately 85% of NH3 emissions are estimated to come
      from agricultural nonpoint sources. We suspect a strong seasonal pattern in NH 3
      emissions; however, current NH3 emission inventories lack intra-annual
      variability. Annually averaged NH 3 emissions could significantly affect model
      predicted concentrations and wet and dry deposition of nitrogen-containing
      compounds. We apply a Kalman filter inverse modeling technique to deduce monthly
      NH3 emissions for the eastern U.S. Final products of this research will include
      monthly emissions estimates from each season. Results for January and June 1990
      are currently available and are presented here. The U.S. Environmental Protection
      Agency (USEPA) Community Multiscale Air Quality (CMAQ) model and ammonium (NH4+)
      wet concentration data from the National Atmospheric Deposition Program (NADP)
      network are used. The inverse modeling technique estimates the emission
      adjustments that provide optimal modeled results with respect to wet NH4+
      concentrations, observational data error, and emission uncertainty. Our results
      suggest that annual average NH 3 emissions estimates should be decreased by 64%
      for January 1990 and increased by 25% for June 1990. These results illustrate the
      strong differences that are anticipated for NH3 emissions.

PMID- 12805798
TI  - Implementing a voluntary, nonregulatory approach to nitrogen management in Tampa
      Bay, FL: a public/private partnership.
AB  - Participants in the Tampa Bay Estuary Program have agreed to adopt nitrogen
      loading targets for Tampa Bay based on the water-quality and related light
      requirements of underwater seagrasses. Based on modeling results, it appears that
      light levels can be maintained at necessary levels by "holding the line" at
      existing nitrogen loadings; however, this goal may be difficult to achieve given
      the 20% increase in the watershed"s human population and associated 7% increase
      in nitrogen loading that are projected to occur over the next 20 years. To
      address the long-term management of nitrogen sources, a nitrogen management
      consortium of local electric utilities, industries, and agricultural interests,
      as well as local governments and regulatory agency representatives, has developed
      a consortium action plan to address the target load reduction needed to "hold the
      line" at 1992 to 1994 levels. To date, implemented and planned projects collated
      in the Consortium Action Plan meet and exceed the agreed-upon nitrogen-loading
      reduction goal. An example of the success of the private partnership aspect of
      this program can be seen in three phosphate fertilizer mining and manufacturing
      companies with facilities located on Tampa Bay. These companies are participants
      in the Estuary Program and the Nitrogen Management Consortium to provide support
      and input for a program that advocates voluntary, nonregulatory cooperation to
      reach environmental goals.

PMID- 12805799
TI  - Comparative assessment of groundwater quality in the Tangshan region of the
      People's Republic of China and similar areas in the U.S.
AB  - Groundwater quality with respect to nitrate, major inorganic constituents, stable
      isotopes, and tritium was assessed in the agricultural Tangshan region in the Hai
      He River Basin of the People's Republic of China and compared with three regions
      in the U.S.: the Delmarva Peninsula of Delaware, Maryland, and Virginia; the San
      Joaquin Valley of California; and the Sacramento Valley of California. The China
      and U.S. regions are similar in size and land use, but have different climatic
      conditions and patterns of water use for irrigation. The Tangshan region has been
      in agricultural production for a much longer time, probably several centuries,
      than the three U.S. regions; however, the widespread use of synthetic fertilizers
      and other soil amendments probably started at a similar time in all four regions.
      In all four regions, median nitrate concentrations were generally below the U.S.
      drinking water standard of 10 mg/l of nitrate as nitrogen. However, higher
      concentrations and a greater range were evident for the Tangshan region. In the
      water samples collected from a shallow aquifer in the Tangshan region (over 25%
      of all samples), nitrate concentrations exceeded the Chinese standard of 20 mg/l,
      whereas few comparative samples (2.6%) collected in the U.S. exceeded 20 mg/l. In
      Tangshan, relatively low nitrate, which is indicative of uncontaminated
      background concentrations, was measured in older water of deeper wells. Recently
      recharged water was detected in wells drilled as deep as 150 m. Nitrate
      concentrations above background levels were also measured in water samples from
      these wells. In addition to nitrate, the agricultural area of the Tangshan region
      has been affected by elevated total dissolved solids and iron, the latter
      attributed to widespread application of animal wastes and sewage deposited on the
      land surface, which lead to oxygen depletion in the subsurface environment and
      dissolution of iron. The elevated total dissolved solids of the Tangshan study
      area could not be attributed to any one process.

PMID- 12805800
TI  - Assessments of impacts of nitrogen deposition on beech forests: results from the
      Pan-European Monitoring Programme.
AB  - The article reviews effects of nitrogen (N) deposition on beech forest ecosystems
      in Europe. On the basis of beech plots of the Pan-European Monitoring Programme
      of ICP Forests and the EU, the deposition of N compounds as well as input-output
      budgets are listed and compared with studies in North America. The authors also
      discuss the critical threshold for N leaching. At present, N is leached in 10% of
      the plots evaluated. An in-depth evaluation of a beech plot in central Germany is
      presented. The high N leaching results in a considerable increase (four times
      higher N content in 2000 compared to 1965) in the export of nitrate from the
      beech forests from a nearby source. Finally, ecophysiological indicators (N
      content in beech leaves, fine root system, N content, root/shoot ratios) are
      discussed as a result of high N input.

PMID- 12805801
TI  - A case study of nitrogen saturation in western U.S. forests.
AB  - Virtually complete nitrification of the available ammonium in soil and
      nitrification activity in the forest floor are important factors predisposing
      forests in the San Bernardino Mountains of southern California to nitrogen (N)
      saturation. As a result, inorganic N in the soil solution is dominated by
      nitrate. High nitrification rates also generate elevated nitric oxide (NO)
      emissions from soil. High-base cation saturation of these soils means that soil
      calcium depletion or effects associated with soil acidification are not an
      immediate risk for forest health as has been postulated for mesic forests in the
      eastern U.S. Physiological disturbance (e.g., altered carbon [C] cycling, reduced
      fine root biomass, premature needle abscission) of ozone-sensitive ponderosa pine
      trees exposed to high N deposition and high ozone levels appear to be the greater
      threat to forest sustainability. However, N deposition appears to offset the
      aboveground growth depression effects of ozone exposure. High nitrification
      activity reported for many western ecosystems suggests that with chronic N inputs
      these systems are prone to N saturation and hydrologic and gaseous losses of N.
      High runoff during the winter wet season in California forests under a
      Mediterranean climate may further predispose these watersheds to high nitrate
      leachate losses. After 4 years of N fertilization at a severely N saturated site
      in the San Bernardino Mountains, bole growth unexpectedly increased. Reduced C
      allocation below- ground at this site, presumably in response to ozone or N or
      both pollutants, may enhance the bole growth response to added N.

PMID- 12805802
TI  - Nitrogen export from a watershed subjected to partial salvage logging.
AB  - Logging has been shown to induce nitrogen (N) leaching. We hypothesized that
      logging a watershed that previously exhibited forest decline symptoms would place
      additional stress on the ecosystem and result in greater N loss, compared to
      harvesting vigorous forests. We conducted a 10-year (1988 to 1998) assessment of
      N export from the Baldwin Creek watershed in southwestern Pennsylvania that was
      partially clearcut to salvage dead and dying northern red oak. N export from the
      watershed increased significantly following salvage logging operations and did
      not completely return to prelogging levels by the end of the study period. The
      largest annual NO3-N export of 13 kg/ha was observed during the first year after
      harvesting, an increase of approximately 10 kg/ha. Compared to data from other
      Appalachian Mountain watersheds in North Carolina, West Virginia, and
      Pennsylvania, calculated N loss for Baldwin Creek was considerably greater.
      Longer periods of reduced N uptake due to slow revegetation of salvage logged
      areas, coupled with increased amounts of N available to leaching, could have
      accounted for the large N losses observed for Baldwin Creek. Salvage logging of
      dead and dying trees from forested watersheds in this region appears to have the
      potential to result in much larger N losses than previously reported for harvest
      of healthy stands.

PMID- 12805803
TI  - Input-output budget of nitrogen and the effect of experimentally changed
      deposition in the forest ecosystems in central Japan.
AB  - To evaluate the current nitrogen (N) status in Japanese forests, field
      measurements of rainfall, throughfall, litter layer percolation, and soil
      solution percolation were conducted in a red pine stand (Kannondai) and a
      deciduous stand (Yasato) located in central Japan. N input via throughfall was 31
      and 14 kg ha(-1) year(-1) and output below rooting zone was 9.6 and 5.5 kg ha1
      year(-1) in Kannondai and in Yasato, respectively. Two thirds of input N were
      retained in plant-soil systems. Manipulation of N input was carried out. Ionic
      constituents were removed from throughfall with ion exchange resin at removal
      sites and ammonium nitrate containing twice the N of the throughfall was applied
      at N addition sites periodically. SO4(2-) output below 20-cm soil layer changed
      depending on the input, while NO3- output was regulated mainly by the internal
      cycle and effect of manipulation was undetected. These Japanese stands were
      generally considered to have a larger capacity to assimilate N than NITREX sites
      in Europe. However, N output fluxes had large spatial variability and some sites
      in Kannondai showed high N leaching below rooting zone almost balanced with the
      input via throughfall.

PMID- 12805804
TI  - Is there synchronicity in nitrogen input and output fluxes at the Noland Divide
      Watershed, a small N-saturated forested catchment in the Great Smoky Mountains
      National Park?
AB  - High-elevation red spruce [Picea rubens Sarg.]-Fraser fir [Abies fraseri (Pursh.)
      Poir] forests in the Southern Appalachians currently receive large nitrogen (N)
      inputs via atmospheric deposition (30 kg N ha(-1) year(-1)) but have limited N
      retention capacity due to a combination of stand age, heavy fir mortality caused
      by exotic insect infestations, and numerous gaps caused by windfalls and ice
      storms. This study examined the magnitude and timing of the N fluxes into,
      through, and out of a small, first-order catchment in the Great Smoky Mountains
      National Park. It also examined the role of climatic conditions in causing
      interannual variations in the N output signal. About half of the atmospheric N
      input was exported annually in the streamwater, primarily as nitrate (NO3-N).
      While most incoming ammonium (NH4-N) was retained in the canopy and the forest
      floor, the NO3-N fluxes were very dynamic in space as well as in time. There was
      a clear decoupling between NO3-N input and output fluxes. Atmospheric N input was
      greatest in the growing season while largest NO3-N losses typically occurred in
      the dormant season. Also, as water passed through the various catchment
      compartments, the NO3-N flux declined below the canopy, increased in the upper
      soil due to internal N mineralization and nitrification, and declined again
      deeper in the mineral soil due to plant uptake and microbial processing.
      Temperature control on N production and hydrologic control on NO3-N leaching
      during the growing season likely caused the observed inter-annual variation in
      fall peak NO3-N concentrations and N discharge rates in the stream.

PMID- 12805805
TI  - Regeneration of mature Norway spruce stands: early effects of selective cutting
      and clear cutting on seepage water quality and soil fertility.
AB  - The cutting of trees influences element turnover in the forest ecosystem. The
      reduction of plant uptake, as well as an increased mineralization and
      nitrification due to higher soil temperature and soil moisture, can lead to
      considerable losses of nutrients from the main rooting zone. This may result in a
      reduced soil fertility and a decrease in drinking water quality due to high
      nitrate concentrations in the seepage water. In Bavaria (Germany) selective
      cutting is preferred to clear cutting when initiating the regeneration of Norway
      spruce stands with European beech. This paper summarizes the early effects of
      both forest management practices on soil fertility and seepage water quality for
      three different sites. Shown are the concentrations of nitrogen and base cations
      in the seepage water as well as the water and ion fluxes during the first year
      after tree cut. Nutrient inputs decreased on thinned plots and even more at clear
      cuts. Nitrate concentrations in the seepage water are hardly affected by moderate
      thinning; however, on clear-cuts, the nitrate concentration increases
      significantly, and base cations are lost from the upper mineral soil. This effect
      is less obvious at sites where a dense ground vegetation, which is able to take
      up excess nitrogen, exists.

PMID- 12805806
TI  - The potential of NO3--N utilization by a woody shrub species Lindera triloba: a
      cultivation test to estimate the saturation point of soil NO3--N for plants.
AB  - Responses of seedlings of a shrub species, Lindera triloba, grown in perlite
      culture medium, to nitrate (NO3--N) supply were investigated to estimate the
      saturating point of available NO3--N for plant utilization. NO3--N concentration
      and nitrate reductase activity (NRA) in leaves and roots were used as indicators
      of NO3--N uptake and assimilation by L. triloba. Root NRA increased with NO3--N
      supply when concentrations were low and reached a plateau at high NO3--N
      concentrations. On the other hand, root NO3--N concentration increased linearly
      with NO3--N supply; therefore, it is suggested that NO3--N uptake did not limit
      NO3--N assimilation by L. triloba. In contrast, leaf NRA and leaf NO3--N
      concentration were low and were not influenced by NO3--N supply. This may be
      caused by the lack of transport of NO3--N from roots to leaves. The NO3--N
      retained in perlite was compared with NO3--N pool sizes in soils from a forest
      where L. triloba occurs naturally to estimate the level of NO3--N availability to
      plants in the forest soil. The maximum NO3--N pool size in the forest soil was
      comparable to concentrations at which root NRA reached a plateau in perlite
      cultures. These results indicate that soil NO3--N availability is below the
      saturation point for NO3--N uptake by L. triloba, and it is the limiting factor
      of NO3--N utilization by L. triloba under field conditions in which this species
      naturally occurs.

PMID- 12805807
TI  - Nitrogen deposition and leaching from two forested catchments in Southwest China-
      preliminary data and research needs.
AB  - Increased nitrogen deposition has resulted in increased nitrogen pools and
      nitrogen leaching in European and North American forest soils. The development in
      Asia in general, and China in particular, suggests increased deposition of
      reduced nitrogen from changes in agricultural practices and of oxidized nitrogen
      from rapid growth of the transportation sector. Decreased nitrogen retention in
      forested areas in the future may cause increased NO3- leaching and, thus,
      acidification and eutrophication in surface waters. The differences in climate,
      ecosystems, land use, and deposition history make direct application of knowledge
      from studies in Europe and North America difficult. In Southwest China the
      potential for nitrogen mobilization from forest soils may be high because of the
      warm and humid climate, resulting in high decomposition rates of soil organic
      matter. However, there are very few data available for quantifying the suspected
      potential for increased nitrogen leaching in forest ecosystems. Here we present
      data from two forested catchments, dominated by Masson pine (Pinus massoniana),
      near Guiyang and Chongqing, respectively, in Southwest China. The present
      nitrogen deposition is moderate, estimated in the range from 10 to 40 kg N ha(-1)
      year(-1). The C/N ratios of the soils are generally below 15. Nitrate
      concentrations in soil water are rather variable in space, with highest values of
      several hundred microequivalents per liter. The turnover rate of nitrogen in the
      forest ecosystem is quite high compared to the atmospheric deposition rate. At
      present, nitrate runoff from the catchments is low and intermediate in Guiyang
      and Chongqing, respectively. More research is needed to improve our ability to
      predict future nitrogen leaching from subtropical Asian coniferous forests.

PMID- 12805808
TI  - Effects of surface soil removal on dynamics of dissolved inorganic nitrogen in a
      snow-dominated forest.
AB  - To clarify the effect of vegetation and surface soil removal on dissolved
      inorganic nitrogen (N) dynamics in a snow-dominated forest soil in northern
      Japan, the seasonal fluctuation of N concentrations in soil solution and the
      annual flux of N in soil were investigated at a treated site (in which surface
      soil, including understory vegetation and organic and A horizons, was removed)
      and control sites from July 1998 to June 2000. Nitrate (NO3-) concentration in
      soil solution at the treated site was significantly higher than that of the
      control in the no-snow period, and it was decreased by dilution from melting
      snow. The annual net outputs of NO3- from soil at the treated site and control
      sites were 257 and -12 mmol m(-2) year(-1), and about 57% of the net output at
      the treated site occurred during the snowmelt period. NO3- was transported from
      the upper level to the lower level of soil via water movement during late autumn
      and winter, and it was retained in soil and leached by melt water in early
      spring. Removing vegetation and surface soil resulted in an increase in NO3-
      concentration of soil solution, and snowmelt strongly affected the NO3- leaching
      from treated soil and the NO3- restoration process in a snow-dominated region.

PMID- 12805809
TI  - Soil N fluxes in three contrasting dry tropical forests.
AB  - A comparative study of N fluxes in soil among a dry dipterocarp forest (DDF), a
      dry evergreen forest (DEF), and a hill evergreen forest (HEF) in Thailand was
      done. N fluxes in soil were estimated using an ion exchange resin core method and
      a buried bag method. Soil C and N pools were 38 C Mg/ha/30 cm and 2.5 N Mg/ha/30
      cm in DDF, 82 C Mg/ha/30 cm and 6.2 N Mg/ha/30 cm in DEF, and 167 C Mg/ha/30 cm
      and 9.3 N Mg/ha/30 cm in HEF. Low C concentration in the DDF and DEF sites was
      compensated by high fine soil content. In the highly weathered tropical soil,
      fine soil content seemed to be important for C accumulation. Temporal and
      vertical fluctuations of N fluxes were different among the sites. The highest N
      flux was exhibited at the onset of the wet season in DDF, whereas inorganic N
      production and estimated uptake of N were relatively stable during the wet season
      in DEF and HEF. It is suggested that N cycling in soil becomes stable in dry
      tropical forests to intermediate in temperate forests. N deposition may result in
      large changes of N cycling in the DDF and DEF due to low accumulations of C and
      N.

PMID- 12805810
TI  - Nitrate leakage from deciduous forest soils into streams on Kureha Hill, Japan.
AB  - Nitrate leakage from deciduous forest soils into streams was investigated for two
      adjacent hills. Many of the streams on Kureha Hill, located in Toyama City,
      Japan, have extremely high nitrate concentrations. The nitrate concentration of
      Hyakumakidani, one of the streams on Kureha Hill, averaged 158 microeq l(-1) and
      reached 470 microeq l(-1) during an episodic event. In contrast, the streams on
      Imizu Hill, adjacent to Kureha Hill, had low concentrations, below 15 microeq l(
      1). Even during an episode, the nitrate concentrations increased to no more than
      75 microeq l(-1). Both areas have similar blown forest soils, C/N ratios in O
      horizons, and vegetation consisting primarily of deciduous trees. However, soil
      incubation experiments, which lasted for 4 weeks, revealed that the nitrification
      rates in the surface soils of Kureha Hill were much higher than in the soils of
      Imizu Hill.

PMID- 12805811
TI  - Nitrate in polluted mountainous catchments with Mediterranean climates.
AB  - The mountains of southern California receive some of the highest rates of
      nitrogen (N) deposition in the world (approximately 40 kg ha(-1) year(-1)). These
      high rates of deposition have translated into consistently high levels of nitrate
      (NO3-) in some streams of the San Bernardino Mountains. However, not all streams
      are exhibiting these high levels of NO3-. Perennial streams have high NO3-
      concentrations (approximately 200 micromoles l(-1)) while ephemeral streams do
      not (approximately 20 micromoles l(-1)). This difference points to groundwater as
      the source of the NO3- observed in streams. Furthermore, the evidence indicates a
      differential impact of N deposition on terrestrial and aquatic systems in
      Mediterranean climates, with aquatic systems being impacted more quickly. The
      primary reason for this difference involves the asynchrony between the time that
      atmospheric deposition occurs (summer), the time period of maximum soil NO3-
      availability and leaching (winter), and the time of maximum plant N demand
      (spring). Our results indicate that semiarid Mediterranean climate systems behave
      differently from more humid systems in that, because of this asynchrony, aquatic
      systems may not be indicative of changes in terrestrial ecosystem response. These
      differences lead us to the conclusion that the extrapolation of impacts from
      humid to Mediterranean climates is problematic and the concept of N saturation
      may need to be revisited for semiarid and seasonally dry systems.

PMID- 12805812
TI  - Regional comparison of nitrogen export to Japanese forest streams.
AB  - Nitrogen (N) emissions in Asian countries are predicted to increase over the next
      several decades. An understanding of the mechanisms that control temporal and
      spatial fluctuation of N export to forest streams is important not only to
      quantify critical loads of N, N saturation status, and soil acidification N
      dynamics and budgets in Japanese forested watersheds is not clear due to the lack
      of regional comparative studies on stream N chemistry. To address the lack of
      comparative studies, we measured inorganic N (nitrate and ammonium)
      concentrations from June 2000 to May 2001 in streams in 18 experimental forests
      located throughout the Japanese archipelago and belonging to the Japanese Union
      of University Forests. N concentrations in stream water during base flow and high
      flow periods were monitored, and N mineralization potential in soil was measured
      using batch incubation experiments. Higher nitrate concentrations in stream water
      were present in central Japan, an area that receives high rates of atmospheric N
      deposition. In northern Japan, snowmelt resulted in increased nitrate
      concentrations in stream water. The potential net N mineralization rate was
      higher in surface soil than in subsurface soil, and the high potential for N
      mineralization in the surface soil partly contributed to the increase in nitrate
      concentration in stream water during a storm event. Regional differences in the
      atmospheric N deposition and seasonality of precipitation and high discharge are
      principal controls on the concentrations and variations of nitrates in stream
      water in forested watersheds of Japan.

PMID- 12805813
TI  - Ecosystem processes and nitrogen export in northern U.S. watersheds.
AB  - There is much interest in the relationship of atmospheric nitrogen (N) inputs to
      ecosystem outputs as an indicator of possible "nitrogen saturation" by human
      activity. Longer-term, ecosystem-level mass balance studies suggest that the
      relationship is not clear and that other ecosystem processes may dominate
      variation in N outputs. We have been studying small, forested watershed
      ecosystems in five northern watersheds for periods up to 35 years. Here I
      summarize the research on ecosystem processes and the N budget. During the past 2
      decades, average wet-precipitation N inputs ranged from about 0.1 to 6 kg N ha(
      1) year(-1) among sites. In general, sites with the lowest N inputs had the
      highest output-to-input ratios. In the Alaska watersheds, streamwater N output
      exceeded inputs by 70 to 250%. The ratio of mean monthly headwater nitrate (NO3-)
      concentration to precipitation NO3- concentration declined with increased
      precipitation concentration. A series of ecosystem processes have been studied
      and related to N outputs. The most important appear to be seasonal change in
      hydrologic flowpath, soil freezing, seasonal forest-floor inorganic N pools
      resulting from over-winter mineralization beneath the snowpack, spatial variation
      in watershed forest-floor inorganic N pools, the degree to which snowmelt
      percolates soils, and gross soil N mineralization rates.

PMID- 12805814
TI  - Inorganic and organic losses of nitrogen from upland regions of Britain:
      concentrations and fluxes.
AB  - The nitrogen (N) composition of streams draining eight upland regions of Britain
      was compared using monthly samples collected between April 1997 and April 1998.
      Stream samples were analysed for total N (TN), particulate N (PN), nitrate (NO3),
      ammonium (NH4), and dissolved organic nitrogen (DON). Concentrations of TN were
      small, generally less than 1.5 mg N l(-1), were dominated by dissolved forms of
      N, and varied significantly between regions. NO3 accounted for the majority of
      variability. Concentrations of DON also varied between regions but to a smaller
      extent than those of NO3. There were considerable variations in TN fluxes between
      upland regions, which ranged between 3.8 and 16.1 kg N ha(-1) year(-1). The
      majority of the variation was due to NO3 fluxes, which were largest in regions
      receiving largest inputs of atmospheric N deposition and ranged between 1.4 and
      13.5 kg N ha(-1) year(-1). Fluxes of DON ranged between 1 and 3.5 kg N ha(-1)
      year( -1), while fluxes of PN were generally less than 0.5 kg N ha(-1) year(-1) ,
      and NH4 fluxes ranged between 0.1 and 0.4 kg N ha(-1) year(-1). NO3 was the
      dominant fraction (47-84%) of N exported from all upland regions except the
      Highlands, where DON accounted for 52% of the TN flux. This study has shown that
      the DON fraction is an important component of the total N transported by upland
      streams in Britain.

PMID- 12805815
TI  - A model study on the role of wetland zones in lake eutrophication and
      restoration.
AB  - Shallow lakes respond in different ways to changes in nutrient loading (nitrogen,
      phosphorus). These lakes may be in two different states: turbid, dominated by
      phytoplankton, and clear, dominated by submerged macrophytes. Both states are
      self-stabilizing; a shift from turbid to clear occurs at much lower nutrient
      loading than a shift in the opposite direction. These critical loading levels
      vary among lakes and are dependent on morphological, biological, and lake
      management factors. This paper focuses on the role of wetland zones. Several
      processes are important: transport and settling of suspended solids,
      denitrification, nutrient uptake by marsh vegetation (increasing nutrient
      retention), and improvement of habitat conditions for predatory fish. A
      conceptual model of a lake with surrounding reed marsh was made, including these
      relations. The lake-part of this model consists of an existing lake model named
      PCLake. The relative area of lake and marsh can be varied. Model calculations
      revealed that nutrient concentrations are lowered by the presence of a marsh
      area, and that the critical loading level for a shift to clear water is
      increased. This happens only if the mixing rate of the lake and marsh water is
      adequate. In general, the relative marsh area should be quite large in order to
      have a substantial effect. Export of nutrients can be enhanced by harvesting of
      reed vegetation. Optimal predatory fish stock contributes to water quality
      improvement, but only if combined with favourable loading and physical
      conditions. Within limits, the presence of a wetland zone around lakes may thus
      increase the ability of lakes to cope with nutrients and enhance restoration.
      Validation of the conclusions in real lakes is recommended, a task hampered by
      the fact that, in the Netherlands, many wetland zones have disappeared in the
      past.

PMID- 12805816
TI  - Land use and stream nitrogen concentrations in agricultural watersheds along the
      central coast of California.
AB  - In coastal California nitrogen (N) in runoff from urban and agricultural land is
      suspected to impair surface water quality of creeks and rivers that discharge
      into the Monterey Bay Sanctuary. However, quantitative data on the impacts of
      land use activities on water quality are largely limited to unpublished reports
      and do not estimate N loading. We report on spatial and temporal patterns of N
      concentrations for several coastal creeks and rivers in central California.
      During the 2001 water year, we estimated that the Pajaro River at Chittenden
      exported 302.4 Mg of total N. Nitrate-N concentrations were typically <1 mg N l(
      1) in grazing lands, oak woodlands, and forests, but increased to a range of 1 to
      20 mg N l(-1) as surface waters passed through agricultural lands. Very high
      concentrations of nitrate (in excess of 80 mg N l(-1)) were found in selected
      agricultural ditches that received drainage from tiles (buried perforated pipes).
      Nitrate concentrations in these ditches remained high throughout the winter and
      spring, indicating nitrate was not being flushed out of the soil profile. We
      believe unused N fertilizer has accumulated in the shallow groundwater through
      many cropping cycles. Results are being used to organize landowners, resource
      managers, and growers to develop voluntary monitoring and water quality
      protection plans.

PMID- 12805817
TI  - Nitrogen retention in headwater streams: the influence of groundwater-surface
      water exchange.
AB  - Groundwater-surface water (GW-SW) interaction lengthens hydraulic residence
      times, increases contact between solutes and biologically active surfaces, and
      often creates a gradient of redox conditions conducive to an array of
      biogeochemical processes. As such, the interaction of hydraulic patterns and
      biogeochemical activity is suspected to be an important determinant of elemental
      spiraling in streams. Hydrologic interactions may be particularly important in
      headwater streams, where the extent of the GW-SW mixing environment (i.e.,
      hyporheic zone) is proportionately greater than in larger streams. From our
      current understanding of stream ecosystem function, we discuss nitrogen (N)
      spiraling, present a conceptual model of N retention in streams, and use both of
      these issues to generate specific research questions and testable hypotheses
      regarding N dynamics in streams.

PMID- 12805818
TI  - Global pollution of surface waters from point and nonpoint sources of nitrogen.
AB  - Global 0.5- by 0.5-degree resolution estimates are presented on the fate of
      nitrogen (N) stemming from point and nonpoint sources, including plant uptake,
      denitrification, leaching from the rooting zone, rapid flow through shallow
      groundwater, and slow flow through deep groundwater to riverine systems.
      Historical N inputs are used to describe the N flows in groundwater. For nonpoint
      N sources (agricultural and natural ecosystems), calculations are based on local
      hydrology, climate, geology, soils, climate and land use combined with data for
      1995 on crop production, N inputs from N fertilizers and animal manure, and
      estimates for ammonia emissions, biological N fixation, and N deposition. For
      point sources, our estimates are based on population densities and human N
      emissions, sanitation, and treatment. The results provide a first insight into
      the magnitude of the N losses from soil-plant systems and point sources in
      various parts of the world, and the fate of N during transport in atmosphere,
      groundwater, and surface water. The contribution to the river N load by
      anthropogenic N pollution is dominant in many river basins in Europe, Asia, and
      North Africa. Our model results explain much of the variation in measured N
      export from different world river basins.

PMID- 12805819
TI  - Impact of a first-order riparian zone on nitrogen removal and export from an
      agricultural ecosystem.
AB  - Riparian zones are reputed to be effective at preventing export of agricultural
      groundwater nitrogen (N) from local ecosystems. This is one impetus behind
      riparian zone regulations and initiatives. However, riparian zone function can
      vary under different conditions, with varying impacts on the regional (and
      ultimately global) environment. Rates of groundwater delivery to the surface
      appear to have significant effects on the N-removing capabilities of a riparian
      zone. Research conducted at a first-order agricultural watershed with a well
      defined riparian zone in the Maryland coastal plain indicates that more than 2.5
      kg/day of nitrate-N can be exported under moderate-to-high stream baseflow
      conditions. The total nitrate-N load that exits the system increases with
      increasing flow not simply because of the greater volume of water export. Stream
      water nitrate-N concentrations also increase by more than an order of magnitude
      as flow increases, at least during baseflow. This appears to be largely the
      result of changes in dominant groundwater delivery mechanisms. Higher rates of
      groundwater exfiltration lessen the contact time between nitrate-carrying
      groundwater and potentially reducing riparian soils. Subsurface preferential flow
      paths, in the wetland and adjacent field, also strongly influence N removal.
      Simple assumptions regarding riparian zone function may be inadequate because of
      complexities observed in response to changing hydrologic conditions.

PMID- 12805820
TI  - N management of European grasslands: can the exchange of gaseous N species be
      influenced at the operational level?
AB  - Grassland ecosystems can be regarded as biochemical reactors in which large
      amounts of organic nitrogen (N) are converted into inorganic N, and vice versa.
      If managed in a sustainable manner, grasslands should operate in a quasi steady
      state, characterized by an almost perfect balance between total N input and
      output. As a consequence, the exchange of gaseous N species (NH3, NO, NO2, N2O,
      and N2) between grasslands and the atmosphere is very small compared to the total
      N turnover. In this study, the effects of two management options (mowing and
      fertilization) on production and emission of nitrous oxide (N2O) from a
      grass/clover crop were examined on the basis of observations and model results
      referring to an experiment carried out on the Swiss Plateau in late summer of
      2000. It was found that production and emission of N2O induced by mowing were of
      the same order of magnitude as those brought about by fertilization, suggesting a
      possible transfer of N from clover to the soil after defoliation. Emissions were
      strongly modulated by precipitation on time scales ranging from 1 day to 1 week.
      This indicates that effective control of N2O emissions through management on a
      day-to-day basis requires reliable medium-range weather forecasts. Model
      calculations were not able to reproduce essential characteristics of the
      emissions. The model slightly overestimated the background emissions, but
      severely underestimated the emission peaks following fertilizer application, and
      largely failed to reproduce emission induced by mowing. Shortfalls in the model
      used for this study were found in relation to the description of soil-water
      fluxes, soil organic matter, and the physiology of clover.

PMID- 12805821
TI  - Modeled impacts of farming practices and structural agricultural changes on
      nitrogen fluxes in the Netherlands.
AB  - In the Netherlands, nutrient emissions from intensive animal husbandry have
      contributed to decreased species diversity in (semi) natural terrestrial and
      aquatic ecosystems, pollution of groundwater, and possibly global warming due to
      N2O emissions. This paper presents the results of a modelling study presenting
      the impacts of both structural measures and improved farming practices on major
      nitrogen (N) fluxes, including NH3 and N2O emission, uptake, leaching, and
      runoff, in the Netherlands, using input data for the year 2000. Average annual
      fluxes (Gg N year(-1)) for the year 2000 were estimated at 132 for NH3 emission
      (160 Gg NH 3 year(-1)), 28 for N2O emission, 50 for N inflow to groundwater, and
      15 for N inflow to surface water at a total N input of 1046. At this input,
      nitrate (NO3) concentrations in groundwater often exceeded the target of 50 mg
      NO3 l(-1), specifically in well-drained sandy soils. The ammonia (NH3) emissions
      exceeded emission targets that were set to protect the biodiversity of
      nonagricultural land. Improved farming practices were calculated to lead to a
      significant reduction in NH3 emissions to the atmosphere and N leaching and
      runoff to groundwater and surface water, but these improvements were not enough
      to reach all the targets set for those fluxes. Only strong structural measures
      clearly improved the situation. The NH3 emission target of 30 Gg NH3 year(-1),
      suggested for the year 2030, could not be attained, however, unless pig and
      poultry farming is completely banned in the Netherlands and all cattle stay
      almost permanently in low emission stables.

PMID- 12805822
TI  - Increasing nitrogen use efficiency of corn in midwestern cropping systems.
AB  - Nitrogen (N) loss from agricultural systems raises concerns about the potential
      impact of farming practices on environmental quality. N is a critical input to
      agricultural production. However, there is little understanding of the
      interactions among crop water use, N application rates, and soil types. This
      study was designed to quantify these interactions in corn ( Zea mays L.) grown in
      production-size fields in central Iowa on the Clarion-Nicollet-Webster soil
      association. Seasonal water use varied by soil type and N application rate. Yield
      varied with N application rate, with the highest average yield obtained at 100 kg
      ha(-1). N use efficiency (NUE) decreased with increasing N application rates,
      having values around 50%. Water use efficiency (WUE) decreased as N fertilizer
      rates increased. Analysis of plant growth patterns showed that in the low organic
      matter soils (lower water-holding capacities), potential yield was not achieved
      because of water deficits during the grain-filling period. Using precipitation
      data coupled with daily water use throughout the season, lower organic matter
      soils showed these soils began to drain earlier in the spring and continued to
      drain more water throughout the season. The low NUE in these soils together with
      increased drainage lead to greater N loss from these soils. Improved management
      decisions have shown that it is possible to couple water use patterns with N
      application to increase both WUE and NUE.

PMID- 12805823
TI  - Response of Acala cotton to nitrogen rates in the San Joaquin Valley of
      California.
AB  - The responses of Acala cotton (Gossypium hirsutum L.) in California to a range of
      applied nitrogen (N) treatments were investigated in a 5-year, multisite
      experiment. The experiment's goals were to identify crop growth and yield
      responses to applied N and provide information to better assess the utility of
      soil residual N estimates in improving fertilizer management. Baseline fertilizer
      application rates for the lowest applied N treatments were based on residual soil
      nitrate-N (NO3-N) levels determined on soil samples from the upper 0.6 m of the
      soil collected prior to spring N fertilization and within 1 week postplanting
      each year. Results have shown positive cotton lint yield responses to increases
      in applied N across the 56 to 224 kg N/ha range in only 41% (16 out of 39) of
      test sites. Soil NO3-N monitoring to a depth of 2.4 m in the spring (after
      planting) and fall (postharvest) indicate most changes in soil NO3- occur within
      the upper 1.2 m of soil. However, some sites (those most prone to leaching losses
      of soluble nutrients) also exhibited net increases in soil NO3-N in the 1.2- to
      2.4-m depth zone when comparing planting time vs. postharvest data. The lack of
      yield responses and soil NO3-N accumulations at some sites indicate that more
      efforts should be put into identifying the amount of plant N requirements that
      can be met from residual soil N, rather than solely from fertilizer N
      applications.

PMID- 12805824
TI  - An Internet-based simulation model for nitrogen management in agricultural
      settings.
AB  - Complex chemical, physical, and biological processes mediate nitrogen (N)
      transformations and movement during agricultural production, making the
      optimization of fertilizer use and environmental protection exceedingly
      difficult. Various computer models have been developed to simulate the site
      specific fate and transport of N resulting from different crop production
      scenarios, but these models are very complex and difficult to use for most
      farmers, consultants, and conservationists. In an effort to facilitate access and
      simplify the use of sophisticated models, the U.S. Department of Agriculture
      (USDA) has developed an Internet-based nitrogen analysis tool. Based on the
      Nitrate Leaching and Economic Analysis Package (NLEAP), the Web site allows a
      user to conduct multiyear N simulation modeling specific to a crop field. Servers
      handle much of the required data assembly and formatting, thus sparing the user"s
      resources. Model runs are executed on the servers and the results are transmitted
      to the user. This new tool is presented along with early implementation results.

PMID- 12805825
TI  - Merging nitrogen management and renewable energy needs.
AB  - The ARBRE (ARable Biomass Renewable Energy) project, the first large-scale wood
      fueled electricity generating plant in the U.K., represents a significant
      development in realising British and European policy objectives on renewable
      energy. The plant is fueled by a mix of wood from short rotation coppice (SRC)
      and forest residues. Where feasible, composted/conditioned sewage sludge is
      applied to coppice sites to increase yields and improve soil structure. In the
      Yorkshire Water region, typical total N:P:K composition of composted/conditioned
      sludge is 2.9:3.8:0.3, respectively. Sludge application is calculated on the
      basis of total nitrogen (N) content to achieve 750 kg N ha(-1), for 3 years"
      requirement. Willow coppice forms a dense, widely spaced, root network, which,
      with its long growing season, makes it an effective user of nutrients. This, in
      combination with willow"s use as a nonfood, nonfodder crop, makes it an
      attractive route for the recycling of sewage sludge in the absence of sea
      disposal, banned under the EC Urban Waste Water Treatment Directive (UWWTD).
      Further work is required on the nutritional requirements of SRC in order to
      understand better the quantities of sludge that can be applied to SRC without
      having a detrimental impact on the environment. This paper suggests the source of
      N rerouting under the UWWTD and suggests the likely expansion of SRC as an
      alternative recycling pathway.

PMID- 12805826
TI  - Nutrient management programs, nitrogen fertilizer practices, and groundwater
      quality in Nebraska's Central Platte Valley (U.S.), 1989-1998.
AB  - Given the societal concern about groundwater pollution from agricultural sources,
      public programs have been proposed or implemented to change farmer behavior with
      respect to nutrient use and management. However, few of these programs designed
      to change farmer behavior have been evaluated due to the lack of detailed data
      over an appropriate time frame. The Central Platte Natural Resources District
      (CPNRD) in Nebraska has identified an intensively cultivated, irrigated area with
      average groundwater nitrate-nitrogen (N) levels about double the EPA"s safe
      drinking water standard. The CPNRD implemented a joint education and regulatory N
      management program in the mid-1980s to reduce groundwater N. This analysis
      reports N use and management, yield, and groundwater nitrate trends in the CPNRD
      for nearly 3000 continuous-corn fields from 1989 to 1998, where producers faced
      limits on the timing of N fertilizer application but no limits on amounts.
      Groundwater nitrate levels showed modest improvement over the 10 years of this
      analysis, falling from the 1989-1993 average of 18.9 to 18.1 mg/l during 1994
      1998. The availability of N in excess of crop needs was clearly documented by the
      CPNRD data and was related to optimistic yield goals, irrigation water use above
      expected levels, and lack of adherence to commercial fertilizer application
      guidelines. Over the 10-year period of this analysis, producers reported
      harvesting an annual average of 9729 kg/ha, 1569 kg/ha (14%) below the average
      yield goal. During 1989-1998, producers reported annually applying an average of
      162.5 kg/ha of commercial N fertilizer, 15.7 kg/ha (10%) above the guideline
      level. Including the N contribution from irrigation water, the potential N
      contribution to the environment (total N available less estimated crop use) was
      estimated at 71.7 kg/ha. This is an estimate of the nitrates available for
      denitrification, volatilization, runoff, future soil N, and leaching to
      groundwater. On average, between 1989-1993 and 1994-1998, producers more closely
      followed CPNRD N fertilizer recommendations and increased their use of postemerge
      N applications--an indication of improved synchrony between N availability and
      crop uptake.

PMID- 12805827
TI  - Monitoring nitrogen leaching for the evaluation of the Dutch minerals policy for
      agriculture in clay regions.
AB  - This paper presents the results of the Dutch monitoring program for agriculture
      in the clay regions for the period 1996-2000 and evaluates the monitoring
      strategy. A wide range of farms (25 to 85%) had a NO3--N concentration in tile
      drainwater higher than the EU standard of 11.3 mg/l. The low figure is related to
      wet winters; the high, to dry winters. Arable farms are more prone to NO3-
      leaching than dairy farms. On arable farms, about 25% of the N surplus leached to
      groundwater and tile drainwater, on dairy farms this was about 15%. N in tile
      drainwater has shown to be the best indicator for monitoring the effects of
      farming practice changes in the clay regions. The average NO3--N concentration in
      tile drainwater was 18.8 and 3.2 mg/l in borehole water on farms where both were
      monitored. It is known that N use has a relationship with NO3- in tile drainwater
      and not with NH4+ and organic N. The presented results indicate that crop
      rotation and precipitation strongly influence NO3- concentration in tile
      drainwater.

PMID- 12805828
TI  - Nitrogen Loss Estimation Worksheet (NLEW): an agricultural nitrogen loading
      reduction tracking tool.
AB  - The Neuse River Basin in North Carolina was regulated in 1998, requiring that all
      pollution sources (point and nonpoint) reduce nitrogen (N) loading into the Neuse
      Estuary by 30%. Point source N reductions have already been reduced by
      approximately 35%. The diffuse nature of nonpoint source pollution, and its
      spatial and temporal variability, makes it a more difficult problem to treat.
      Agriculture is believed to contribute over 50% of the total N load to the river.
      In order to reduce these N inputs, best management practices (BMPs) are necessary
      to control the delivery of N from agricultural activities to water resources and
      to prevent impacts to the physical and biological integrity of surface and ground
      water. To provide greater flexibility to the agricultural community beyond
      standard BMPs (nutrient management, riparian buffers, and water-control
      structures), an agricultural N accounting tool, called Nitrogen Loss Estimation
      Worksheet (NLEW), was developed to track N reductions due to BMP implementation.
      NLEW uses a modified N-balance equation that accounts for some N inputs as well
      as N reductions from nutrient management and other BMPs. It works at both the
      field- and county-level scales. The tool has been used by counties to determine
      different N reduction strategies to achieve the 30% targeted reduction.

PMID- 12805829
TI  - Nitrogen exchanges: testing the hypothesis of a country without agricultural
      production.
AB  - Today, finding data on agricultural nitrogen balances is quite easy. Calculations
      of such balances are carried out by most of the European countries as an
      indicator of environmental pollution attributable to the agricultural sector. In
      France, average values of agricultural nitrogen balances show an excess of 1.5 to
      2 million tons of nitrogen. This excess is enormous. What would the balance of a
      country be if agricultural activity were stopped? In the following article, a
      country (France is used as an example) without agriculture is studied in order to
      assess its nitrogen balance. Using a previously published model describing
      nitrogen input and output of a given country, nitrogen flows are identified.
      Inputs include deposition, fixation, and products not intended for agricultural
      use. Outputs are reduced to zero if agriculture disappears (in France,
      agriculture is the only sector exporting products containing nitrogen). All flows
      are calculated considering the hypothesis of disappearance of agriculture.
      Nitrogen requirements to feed people and pets in France are estimated based on
      medical and veterinary data (recommended daily amounts for proteins and/or usual
      average consumption). Indeed, most of the food that nourishes the French
      population is produced nationally. If agriculture stops, it will be necessary to
      import food from foreign countries. Results show an unexpectedly high excess (for
      a country without agriculture having a structure similar to France: number of
      human beings and pets) of 1.5 million tons of nitrogen. An attempt to calculate
      an agricultural balance with the same data gives a result close to 3 million
      tons. Differences in French agricultural balances found in the literature can
      mainly be explained by values taken into account for deposition and fixation
      (values used here are at least 300,000 tons higher than values used by the
      Organisation for Economic Co-operation and Development). In conclusion, nitrogen
      excess in agriculture is partly due to social demand; agriculture does not only
      produce food but also includes many other functions (landscape management,
      employment, and preservation of culture, for example). As a consequence, efforts
      that do not involve suppressing agriculture should be made to figure out
      alternative ways of production.

PMID- 12805830
TI  - Potential for ammonia recapture by farm woodlands: design and application of a
      new experimental facility.
AB  - There has been increasing pressure on farmers in Europe to reduce the emissions
      of ammonia from their land. Due to the current financial climate in which farmers
      have to operate, it is important to identify ammonia control measures that can be
      adopted with minimum cost. The planting of trees around farmland and buildings
      has been identified as a potentially effective and low-cost measure to enhance
      ammonia recapture at a farm level and reduce long-range atmospheric transport.
      This work assesses experimentally what fraction of ammonia farm woodlands could
      potentially remove from the atmosphere. We constructed an experimental facility
      in southern Scotland to simulate a woodland shelterbelt planted in proximity to a
      small poultry unit. By measuring horizontal and vertical ammonia concentration
      profiles within the woodland, and comparing this to the concentration of an inert
      tracer (SF6) we estimate the depletion of ammonia due to dry deposition to the
      woodland canopy. Together with measurements of mean ammonia concentrations and
      throughfall fluxes of nitrogen, this information is used to provide a first
      estimate of the fraction of emitted ammonia that is recaptured by the woodland
      canopy. Analysis of these data give a lower limit of recapture of emitted
      ammonia, at the experimental facility, of 3%. By careful design of shelterbelt
      woodlands this figure could be significantly higher.

PMID- 12805831
TI  - Spatial distribution of nitrogen on grazed karst landscapes.
AB  - The impact on water quality by agricultural activity in karst terrain is an
      important consideration for resource management within the Appalachian region.
      Karst areas comprise about 18% of the region"s land area. An estimated one-third
      of the region"s farms, cattle, and agricultural market value are located on karst
      terrain. Mean nitrate concentrations in several karst springs in southeastern
      West Virginia exhibit a strong linear relationship with the percentage of
      agriculture land cover. Development of best management practices for efficient
      nitrogen (N) use and reduction of outflow of N to water from karst areas requires
      knowledge about N dynamics on those landscapes. Water extractable NO3-N and NH4-N
      were measured along transects at four soil depths in two grazed sinkholes and one
      wooded sinkhole. Distribution of soil NO3-N and NH4-N were related to frequency
      of animal presence and to topographic and hydrologic redistribution of soil and
      fecal matter in the grazed sinkholes. Karst pastures are characterized by under
      drainage and funneling of water and contaminants to the shallow aquifer. Control
      of NO3-N leaching from karst pasture may depend on management strategies that
      change livestock grazing behavior in sinkholes and reduce the opportunity for
      water and contaminants to quickly reach sinkhole drains.

PMID- 12805832
TI  - N-losses and energy use in a scenario for conversion to organic farming.
AB  - The aims of organic farming include the recycling of nutrients and organic matter
      and the minimisation of the environmental impact of agriculture. Reduced nitrogen
      (N)-losses and energy (E)-use are therefore fundamental objectives of conversion
      to organic farming. However, the case is not straightforward, and different
      scenarios for conversion to organic farming might lead to reduced or increased N
      losses and E-use. This paper presents a scenario tool that uses a Geographical
      Information System in association with models for crop rotations, fertilisation
      practices, N-losses, and E-uses. The scenario tool has been developed within the
      multidisciplinary research project Land Use and Landscape Development Illustrated
      with Scenarios (ARLAS). A pilot scenario was carried out, where predicted changes
      in N-losses and E-uses following conversion to organic farming in areas with
      special interests in clean groundwater were compared. The N-surplus and E-use
      were on average reduced by 10 and 54%, respectively. However, these reductions
      following the predicted changes in crop rotations, livestock densities, and
      fertilisation practices were not large enough to ensure a statistically
      significant reduction at the 95% level. We therefore recommend further research
      in how conversion to organic farming or other changes in the agricultural
      practice might help to reduce N-surpluses and E-uses. In that context, the
      presented scenario tool would be useful.

PMID- 12805833
TI  - Nutritional methods to decrease N losses from open-dirt feedlots in Nebraska.
AB  - Nitrogen (N) losses from cattle feedlots are of concern due to loss of valuable N
      and enrichment of the atmospheric N pool. Nutritional methods to decrease such
      losses would have economic and environmental benefits. One method to decrease N
      losses is by increasing carbon (C) on the pen surface. The most cost effective
      method of decreasing N losses with C may be feeding diets lower in digestibility
      compared to adding C directly to pens. Therefore, three experiments evaluated
      feeding corn bran (which is less digestible than corn) as either 0, 15, or 30% of
      the diet. The 15- and 30%-bran diets increase organic matter (OM) excretion by
      approximately 0.5 and 1.0 kg per steer per day, respectively. Compared with no
      bran, feeding 15 and 30% decreased feed efficiency by 7.8 and 10.4%,
      respectively. Nutrient balance was assessed in two trials from October through
      May and in one trial from June to September. During the trials from October to
      May, N losses were decreased by 14.5 and 20.7% for the 15- and 30%-bran diets
      compared with no bran. Feeding 15 or 30% bran did not influence N losses in the
      experiment from June to September. Increasing the C:N ratio of manure prior to
      cleaning open-dirt feedlots had variable results depending on time of year.

PMID- 12805834
TI  - Prevention and control of losses of gaseous nitrogen compounds in livestock
      operations: a review.
AB  - Nitrogen (N) losses from livestock houses and manure storage facilities
      contribute greatly to the total loss of N from livestock farms. Volatilisation of
      ammonia (NH3) is the major process responsible for the loss of N in husbandry
      systems with slurry (where average dry matter content varies between 3 and 13%).
      Concerning this volatilisation of NH3, the process parameters of pH and air
      temperature are crucial. During a period of approximately 10 years, systematic
      measurements of NH3 losses originating from a large variety of different
      livestock houses were made. One of the problems with NH3 emissions is the large
      variation in the measured data due to the season, the production of the animals,
      the manure treatment, type of livestock house, and the manure storage. Generally
      speaking, prevention and control of NH3 emission can be done by control of N
      content in the manure, moisture content, pH, and temperature. In houses for
      growing pigs, a combination of simple housing measures can be taken to greatly
      reduce NH3 emissions. In houses for laying hens, the control of the manure drying
      process determines the emission of NH3. Monteny has built an NH3 production model
      with separate modules for the emission of the manure storage under the dairy
      house and the floor in the house. Manure spreading is also a major source of NH3
      emission and is dependent on slurry composition, environmental conditions, and
      farm management. The effects of these factors have been employed in a model.
      Losses via NO, N2O, and N2 are important in husbandry systems with solid manure
      and straw. The number of experimental data is, however, very limited. As N2O is
      an intermediate product of complex biochemical processes of nitrification and
      denitrification, optimal conditions are the key issues in N2O reduction
      strategies. We may expect that in the near future the emission of greenhouse
      gases will get the same attention from policy makers as NH3. Sustainable
      livestock production has to combine low emissions of gaseous N compounds with
      acceptable odour emissions, low emissions of greenhouse gases, and acceptable
      standards of animal welfare. For the entrepreneur, the strategy must be built on
      the regulations, the special conditions of his farm, and what is reasonably
      achievable.

PMID- 12805835
TI  - Environmental scenarios for the future nitrogen policy in Flanders, Belgium.
AB  - The agricultural sector accounts for two thirds of nitrogen losses in Flanders,
      Belgium. Since 1991 both the government and the farmers have been taking measures
      to reduce the nitrogen surplus. Initially, the manure policy was aimed at
      distributing the manure surplus equally across Flanders. At the same time, the
      growth of livestock was stopped by a strict licensing policy, which required
      "command and control" measures. In recent years, the policy has switched to the
      use of individual target commitments by farmers. The Flemish manure policy will
      be tightened even more as a result of international pressures. An ex ante
      evaluation of possible policy options was carried out using three different
      scenarios spread out until 2010 (Business As Usual, Additional Measures, and
      Sustainable Development). To do this, a sector-economic, regionalized,
      environmental, comparative static, partial equilibrium, mathematical programming
      model of the Flemish agriculture was developed. The nitrogen emission into the
      agricultural soil was calculated by means of a regional soil balance. European
      targets can only be reached with manure processing, reduced fertilizer usage, and
      a strong reduction of intensive livestock breeding activities. The atmospheric
      deposition of nitrogen compounds will strongly decrease in 2010 if additional
      measures are taken. This will also result in a strong reduction of nitrous oxide
      emissions.

PMID- 12805836
TI  - Synchronizing N release from organic residues: opportunities for integrated
      management of N.
AB  - In intensive cropping systems, mineral nitrogen (N) fertilizers represent the
      largest component of the N cycle because the indigenous N supply is not adequate.
      The requirement for mineral fertilizer may be reduced with the use of organic
      nutrient sources. A more realistic use of organic matter, particularly in sub
      Saharan Africa due to limited amounts and availability, is the combined use of
      organic nutrient sources and mineral fertilizers. The beneficial effects of
      integrated use of inorganic fertilizers and organic manures on improved nutrient
      recoveries, soil moisture retention, cation exchange capacity, and erosion
      control have been reported. However, there are as many reports indicating
      negligible benefits or even disadvantages of combining nutrient sources on crop
      production. This is not surprising given the combination of organic residue
      sources, soils, climatic, crops, and management factors that influence nutrient
      dynamics. The most widely accepted function of organic materials is improving the
      nutrient availability to crops by supplying N. The key to both improving
      efficiency of N use and reducing N losses is synchronization of N supply from
      soil, biological N2 fixation, organic residues, and inorganic fertilizers with
      the crop N demand. Organic materials are not magic; N losses also result from
      their use. Controlling N release from organic sources depends on their nutrient
      content and quality, soil properties, and the environmental and management
      factors. This paper will synthesize the information generated from integrated
      nutrient management trials in sub-Saharan Africa and the Philippines. Management
      strategies based on an organic resources database and a dynamic soil-crop
      simulation model are used to identify organic sources as N fertilizers or soil
      amendments. The decision support tools are also used to attain optimum synchrony
      between release from organic sources and soils with crop N demand.

PMID- 12805837
TI  - Assessment of nitrogen ceilings for Dutch agricultural soils to avoid adverse
      environmental impacts.
AB  - In the Netherlands, high traffic density and intensive animal husbandry have led
      to high emissions of reactive nitrogen (N) into the environment. This leads to a
      series of environmental impacts, including: (1) nitrate (NO3) contamination of
      drinking water, (2) eutrophication of freshwater lakes, (3) acidification and
      biodiversity impacts on terrestrial ecosystems, (4) ozone and particle formation
      affecting human health, and (5) global climate change induced by emissions of
      N2O. Measures to control reactive N emissions were, up to now, directed towards
      those different environmental themes. Here we summarize the results of a study to
      analyse the agricultural N problem in the Netherlands in an integrated way, which
      means that all relevant aspects are taken into account simultaneously. A simple N
      balance model was developed, representing all crucial processes in the N chain,
      to calculate acceptable N inputs to the farm (so-called N ceiling) and to the
      soil surface (application in the field) by feed concentrates, organic manure,
      fertiliser, deposition, and N fixation. The N ceilings were calculated on the
      basis of critical limits for NO 3 concentrations in groundwater, N concentrations
      in surface water, and ammonia (NH3) emission targets related to the protection of
      biodiversity of natural areas. Results show that in most parts of the
      Netherlands, except the western and the northern part, the N ceilings are limited
      by NH 3 emissions, which are derived from critical N loads for nature areas,
      rather than limits for both ground- and surface water. On the national scale, the
      N ceiling ranges between 372 and 858 kton year(-1) depending on the choice of
      critical limits. The current N import is 848 kton year(-1). A decrease of nearly
      60% is needed to reach the ceilings that are necessary to protect the environment
      against all adverse impacts of N pollution from agriculture.

PMID- 12805838
TI  - Temporal changes in nitrogen pollution in northeastern Estonia.
AB  - During the last 5 decades the northeastern part of Estonia (the region where oil
      shale and the chemical industry are located) has been subjected to pollution with
      acidic compounds. In 1981-1988 the yearly mean nitrogen (N) deposition load was
      up to 11.1 kg ha(-1). This N pollution level combined with the deposition of
      sulphur (S) could have seriously endangered the environment, but the simultaneous
      emission of strongly alkaline fly ash restrained acidification processes. After
      1989-1991 the situation changed, and in 1994-1996 the N deposition load in
      northeastern Estonia remained within the range of 2.6 to 6.6 kg ha(-1) year(-1)
      and that of S within 2 to 50 kg ha(-1) year(-1). Because the fly ash deposition
      is permanently decreasing, more sensitive lichens and mosses can be subjected to
      critical N+S loads in the future. The proportion of oil shale industry in total
      emission of NOx in Estonia from stationary sources equals approximately 65 to
      75%. During 1996-2000 the yearly mean concentration of NO2 in the air of towns
      increased from 9 to 12 to 16 to 29 g m(-3). The emission of N compounds was
      mainly caused by N oxides in flue gases from power plants, as well as ammonia and
      carbamide discharges from chemical plants. In 1988-1990 the estimated yearly
      total emission of NOx (as NO2 equivalent) was about 18 to 18.6 thousand t and in
      1994-2000, 9.9 to 11.8 thousand t.

PMID- 12805839
TI  - Past and future exceedances of nitrogen critical loads in Europe.
AB  - Critical loads of acidity and nutrient nitrogen--simple measures of the
      sensitivity of ecosystems to deposition--have been widely used for setting
      emission reduction targets in Europe. In contrast to sulfur, the emissions of
      nitrogen compounds remain high in the future. This is also true for the
      exceedances of critical loads until 2010. Looking further into the future,
      climate change is likely to influence ecosystem sensitivity, and thus critical
      loads. It is shown that higher temperatures, changed precipitation patterns, and
      modified net primary production mainly increase critical loads, except in
      mountainous and arid regions. Using consistent scenarios of climate change and
      air pollution from a recently completed European study (AIR-CLIM), it is shown
      that the exceedances in 2100 of the critical loads are declining in comparison to
      2010. However, exceedances of critical loads of nutrient nitrogen remain
      substantial, even under the most stringent scenario. This confirms the increasing
      role nitrogen plays in environmental problems in comparison to sulfur. Thus
      research should focus on the effects of nitrogen in the environment, especially
      under conditions of climate change, to support nitrogen-emission mitigating
      policies. This not only reduces acidification and eutrophication, but also helps
      curb the formation of tropospheric ozone.

PMID- 12805840
TI  - To trade or not to trade? Criteria for applying cap and trade.
AB  - The use of emissions trading (cap and trade) is gaining worldwide recognition as
      an extremely effective policy tool. The U.S. Sulfur Dioxide (SO2) Emissions
      Trading Program has achieved an unprecedented level of environmental protection
      in a cost-effective manner. The successful results of the program have led
      domestic and foreign governments to consider the application of cap and trade to
      address other air quality issues. Certain analyses are particularly important in
      determining whether or not cap and trade is an appropriate policy tool. This
      paper offers a set of questions that can be used as criteria for determining
      whether or not cap and trade is the preferred policy approach to an environmental
      problem.

PMID- 12805842
TI  - Recent advances in photoluminescence detection of fingerprints.
AB  - Photoluminescence detection of latent fingerprints has over the last quarter
      century brought about a new level of fingerprint detection sensitivity. The
      current state of the art is briefly reviewed to set the stage for upcoming new
      fingerprint processing strategies. These are designed for suppression of
      background fluorescence from articles holding latent prints, an often serious
      problem. The suppression of the background involves time-resolved imaging, which
      is dealt with from the perspective of instrumentation as well as the design of
      fingerprint treatment strategies. These focus on lanthanide chelates,
      nanocrystals, and nanocomposites functionalized to label fingerprints.

PMID- 12805841
TI  - A potential integrated water quality strategy for the Mississippi River Basin and
      the Gulf of Mexico.
AB  - Nutrient pollution, now the leading cause of water quality impairment in the
      U.S., has had significant impact on the nation"s waterways. Excessive nutrient
      pollution has been linked to habitat loss, fish kills, blooms of toxic algae, and
      hypoxia (oxygen-depleted water). The hypoxic "dead zone" in the Gulf of Mexico is
      one of the most striking illustrations of what can happen when too many nutrients
      from inland watersheds reach coastal areas. Despite programs to improve municipal
      wastewater treatment facilities, more stringent industrial wastewater
      requirements, and agricultural programs designed to reduce sediment loads in
      waterways, water quality and nutrient pollution continues to be a problem, and in
      many cases has worsened. We undertook a policy analysis to assess how the
      agricultural community could better reduce its contribution to the dead zone and
      also to evaluate the synergistic impacts of these policies on other environmental
      concerns such as climate change. Using a sectorial model of U.S. agriculture, we
      compared policies including untargeted conservation subsidies, nutrient trading,
      Conservation Reserve Program extension, agricultural sales of carbon and
      greenhouse gas credits, and fertilizer reduction. This economic and environmental
      analysis is watershed-based, primarily focusing on nitrogen in the Mississippi
      River basin, which allowed us to assess the distribution of nitrogen reduction in
      streams, environmental co-benefits, and impact on agricultural cash flows within
      the Mississippi River basin from various options. The model incorporates a number
      of environmental factors, making it possible to get a more a complete picture of
      the costs and co-benefits of nutrient reduction. These elements also help to
      identify the policy options that minimize the costs to farmers and maximize
      benefits to society.

PMID- 12805843
TI  - ASIC3: a lactic acid sensor for cardiac pain.
AB  - Angina, the prototypic vasoocclusive pain, is a radiating chest pain that occurs
      when heart muscle gets insufficient blood because of coronary artery disease.
      Other examples of vasoocclusive pain include the acute pain of heart attack and
      the intermittent pains that accompany sickle cell anemia and peripheral artery
      disease. All these conditions cause ischemia - insufficient oxygen delivery for
      local metabolic demand - and this releases lactic acid as cells switch to
      anaerobic metabolism. Recent discoveries demonstrate that sensory neurons
      innervating the heart are richly endowed with an ion channel that is opened by,
      and perfectly tuned for, the lactic acid released by muscle ischemia.

PMID- 12805844
TI  - Development and types of passive samplers for monitoring atmospheric NO2 and NH3
      concentrations.
AB  - Numerous passive samplers based on the "Palmes-tube" have been developed for
      ambient air monitoring. In each case, the diffusion path length and/or cross
      sectional area are modified to achieve the desired sampling rate. "Tube-type"
      samplers are low sensitivity samplers suitable for long-term monitoring, whereas
      the "badge-type" samplers have faster sampling rates suited to short-term
      monitoring. In the U.K., diffusion tubes are widely used for monitoring nitrogen
      dioxide (NO2) and ammonia (NH3). The open-ended diffusion tubes are prone to
      positive bias caused by incursion of wind eddies, leading to a shortening of the
      diffusion path. By using a porous membrane at the inlet, wind incursion is
      prevented, but an additional diffusion resistance is imposed and it is necessary
      to calibrate the tubes against a reference method to obtain an effective sampling
      rate. For NO2 sampling, positive bias also arises from the reaction of NO with O3
      within the sampler. The interference from the chemical reaction is severe close
      to NO sources, with errors up to 30% for curbside locations when using the "tube
      type" sampler. In rural areas, where NO concentrations are small relative to NO2,
      these errors are small. In some implementations, there is also a negative bias
      over long sampling periods caused by the degradation of trapped NO2. The low
      sampling rates of diffusion tubes make them too uncertain for use at background
      NH3 concentrations (<1 microg NH3 m(-3)) where they significantly overestimate
      concentrations. Badge-type samplers such as the "Willems badge" samplers permit
      accurate sampling at low ambient NH3 concentrations, but suffer from saturation
      at high concentrations and sensitivity to wind speed. A passive sampler optimised
      for monthly measurements of NH3 is reported here, together with its application
      in the U.K. National Ammonia Monitoring Network.

PMID- 12805845
TI  - Calcineurin, synaptic plasticity, and memory.

PMID- 12805846
TI  - Diversity, biodiversity, conservation, and sustainability.
AB  - The concepts of diversity and biodiversity are analysed regarding their
      historical emergence, and their intrinsic meaning and differences are discussed.
      Through a brief synopsis, difficulties usually experienced by statisticians in
      capturing the dynamics of diversity are analysed and main problems identified.
      The shift from diversity to the more holistic biodiversity as a working concept
      is appraised in terms of the novelty involved. Through a number of examples, the
      way the two concepts capture natural cyclic changes is analysed, and their
      reciprocal and complementary relations are approached theoretically. The way
      diversity could develop from the stores of biodiversity as its active expression
      through selective and evolutionary processes is described. Through the use of a
      very simple dynamic model, the concepts of diversity and biodiversity are
      analysed in extremely opposite hypothetical scenarios. Comparisons with natural
      situations are made and the theoretical implications from the conservation point
      of view are discussed. These support the opinion that conservation undertaken in
      restricted and protected areas is not self-sustainable, needing permanent
      external intervention to regulate internal processes, and in the long run will
      most probably lead in the direction of obsolescence and extinction. Finally, the
      relations between diversity, biodiversity, and sustainability are approached. The
      vagueness of the sustainability concept is discussed. Preservation of
      biodiversity is then defended as one of the best available indicators to assist
      us in fixing boundaries which may help to provide a more precise definition of
      sustainability.

PMID- 12805847
TI  - Reversing the negative genomic effects of aging with short-term calorie
      restriction.
AB  - According to government figures, total health care spending in the U.S. in 1999
      was 1.316 trillion dollars. The government projects an increase in health care
      costs to 2.176 trillion dollars by 2008. If we project this growth rate to 2020,
      health care costs will reach 4.009 trillion dollars. Today, people often spend
      more health care dollars during the last year of their lives than in all previous
      years combined. Medical treatment in the last few years of life is usually very
      expensive and often futile. With the baby-boom generation now moving through
      middle age, the prescription for the U.S. health care system will be disastrous
      unless we learn how to keep people healthier longer. This dramatic increase in
      health care costs leaves us with only one acceptable alternative to rationed
      health care or financial ruin--to discover interventions that make people
      functionally younger, healthier, and less susceptible to debilitating, age
      related diseases.

PMID- 12805848
TI  - An explanation of shortening heat generation and mechanical performance
      enhancement during muscle stretch.
AB  - Titin is an extraordinary long multidomain protein spanning half of the
      sarcomeric unit. One end of the titin filament is known to emerge from the Z
      line, but the precise localization of the other end is still a matter of debate.
      Assuming that titin filaments connect the Z-line to the tips of thin filaments in
      the opposite half of the sarcomere, the behavior of an actively contracting
      muscle during mechanical stretch, as well as the mechanism of muscle shortening
      heat generation, can be easily explained if one considers that titin filaments
      are involved not only in the passive elasticity of the muscle but also in the
      force and heat generation during contraction.

PMID- 12805849
TI  - Sympathetic prions.
AB  - Transmissible spongiform encephalopathies are a group of invariably fatal
      neurodegenerative diseases. The infectious agent is termed prion and is thought
      to be composed of a modified protein (PrP Sc or Pr PRES ), a protease-resistant
      conformer of the normal host-encoded membrane glycoprotein, PrP C. Bovine
      spongiform encephalopathy, scrapie of sheep, and Creutzfeldt-Jakob disease are
      among the most notable transmissible spongiform encephalopathies. Prions are most
      efficiently propagated trough intracerebral inoculation, yet the entry point of
      the infectious agent is often through peripheral sites like the gastrointestinal
      tract. The process by which prions invade the brain is termed neuroinvasion. We
      and others have speculated that, depending on the amount of infectious agent
      injected, the injection site, and the strain of prions employed, neuroinvasion
      can occur either directly via peripheral nerves or first through the
      lymphoreticular system and then via peripheral nerves.

PMID- 12805850
TI  - Atmospheric sampling of persistent organic pollutants: needs, applications and
      advances in passive air sampling techniques.
AB  - There are numerous potential applications for validated passive sampling
      techniques to measure persistent organic pollutants (POPs) in the atmosphere, but
      such techniques are still in their infancy. Potential uses include: monitoring to
      check for regulatory compliance and identification of potential sources;
      cheap/efficient reconnaissance surveying of the spatial distribution of POPs; and
      deployment in studies to investigate environmental processes affecting POP
      cycling. This article reviews and discusses the principles and needs of passive
      sampling methodologies. The timescales required for analytical purposes and for
      the scientific objectives of the study are critical in the choice and design of a
      passive sampler. Some techniques may operate over the timescales of hours/days,
      others over weeks/months/years. We distinguish between approaches based on
      "kinetic uptake" and "equilibrium partitioning". We highlight potentially useful
      techniques and discuss their potential advantages, disadvantages, and research
      requirements, drawing attention to the urgent need for detailed studies of
      sampler performance and calibration.

PMID- 12805851
TI  - Environment as a risk factor for male infertility.
AB  - Infertility affects 15% of couples in Western countries. Infertility is defined
      as the inability to conceive after 1 year of attempts without contraception, but
      it is not synonymous with sterility. Between 30 and 50% of infertile couples are
      infertile due to male reasons, mainly due to sperm production disorders. Although
      some risk factors, most of which are infectious, have been identified, there is
      still much uncertainty about the origins of male infertility.

PMID- 12805852
TI  - The marine food chain in relation to biodiversity.
AB  - Biodiversity provides "raw materials" for the food chain and seafood production,
      and also influences the capacity of ecosystems to perform these and other
      services. Harvested marine seafood species now exceed 100 million t y(-1) and
      provide about 6% of all protein and 17% of animal protein consumed by humans.
      These resources include representatives from about nine biologically diverse
      groups of plants and animals. Fish account for most of the world"s marine
      catches, of which only 40 species are taken in abundance. Highest primary
      productivity and the richest fisheries are found within Exclusive Economic Zones
      (EEZ). This narrow strip (200 nautical mile/370 km wide) is not only the site of
      coastal "food factories" but also the area associated with heaviest perturbation
      to the marine environment. Structural redundancy is evident in marine ecosystems,
      in that many species are interchangeable in the way they characterise assemblage
      composition. While there is probably functional redundancy within groups, the
      effects of species loss on ecosystem performance cannot be easily predicted. In
      particular, the degree to which biodiversity per se is needed for ecosystem
      services, including seafood/fishery production, is poorly understood. Many human
      activities, including unsustainable fishing and mariculture, lead to erosion of
      marine biodiversity. This can undermine the biophysical cornerstones of fisheries
      and have other undesirable environmental side effects. Of direct concern are
      "species effects", in particular the removal of target and non-target fishery
      species, as well as conservationally important fauna. Equally disrupting but less
      immediate are "ecosystem effects", such as fishing down the food web, following a
      shift from harvested species of high to low trophic level. Physical and
      biological disturbances from trawl nets and dynamite fishing on coral reefs can
      also severely impact ecosystem structure and function. "Broadscale" biological
      and social effects brought about by fishing carry even more far-reaching
      consequences. For example, fishing itself can change the age at which sexual
      maturity is reached, thus affecting the reproductive status of the stock. Hence,
      fishing may be regarded as a mediator of evolution. Social impacts include
      conflicts over fish prices and policies arising from heavy fishing and inadequate
      institutional structures. Measures to increase the sustainability of catches and
      of biodiversity need to be much more tightly coupled. Promising approaches
      include use of bio-economic indicators and fully protected marine areas. High-
      and local-level governance options are also examined. Use of expert systems
      incorporating "fuzzy logic" are providing useful environmental insights in the
      ASEAN countries and other parts of the world, and have applications in fishery
      management and biodiversity conservation.

PMID- 12805853
TI  - Terrorist attacks: do we know how to assess the results?
AB  - On September 11, 2001, terrorists destroyed the World Trade Center (WTC) in New
      York City. Explosions and fires resulted in the complete collapse of the two WTC
      towers. The collapsing towers served as enormous point sources of gaseous and
      particulate air pollution, seen as huge plumes of smoke and dust. The smoke
      contained volatile organic compounds and fine particles and aerosols. The dust
      fraction contained parts of ceiling tiles, carpets, concrete, adhesives,
      asbestos, chromium, lead, titanium, and many other elements and materials.
      Whether there were unusually toxic ingredients in the plumes is largely unknown.

PMID- 12805854
TI  - Heat shock protein 70 neutralizes apoptosis-inducing factor.
AB  - Programmed cell death (apoptosis) is the physiological process responsible for
      the demise of superfluous, aged, damaged, mutated, and ectopic cells. Its normal
      function is essential both for embryonic development and for maintenance of adult
      tissue homeostasis. Deficient apoptosis participates in cancerogenesis, whereas
      excessive apoptosis leads to unwarranted cell loss accounting for disparate
      diseases including neurodegeneration and AIDS. One critical step in the process
      of apoptosis consists in the permeabilization of mitochondrial membranes, leading
      to the release of proteins which normally are secluded behind the outer
      mitochondrial membrane. For example, cytochrome c, which is normally confined to
      the mitochondrial intermembrane space, is liberated from mitochondria and
      interacts with a cytosolic protein, Apaf-1, causing its oligomerization and
      constitution of the so-called apoptosome, a protein complex which activates a
      specific class of cysteine proteases, the caspases[2]. Another example concerns
      the so-called apoptosis-inducing factor (AIF), another mitochondrial
      intermembrane protein which can translocate to the nucleus where it induces
      chromatin condensation and DNA fragmentation.

PMID- 12805855
TI  - Relationships between passive sampler and continuous ozone (O3 ) measurement data
      in ecological effects research.
AB  - In ecological effects research, there is a rapid increase in the application of
      passive sampling techniques for measuring ambient ozone (O3) concentrations.
      Passive samplers provide data on cumulative exposures of a plant to a pollutant.
      However, O3 is not an accumulative contaminant within the plant tissue, and use
      of prolonged passive sampling durations cannot account for the dynamics of the
      occurrences of O3 that have a significant influence on the plant response.
      Therefore, a stochastic Weibull probability model was previously developed and
      applied to a site in Washington State (1650 m MSL) to simulate the cumulative
      exposure data from a passive sampler, to mimic the corresponding frequency
      distributions of hourly O3 concentrations that would otherwise have been obtained
      by continuous monitoring. At that site the correlation between the actual passive
      sampler and the continuous monitor data was R2 = 0.74. The simulation of the
      hourly O3 data was based on and compared with the results obtained from a
      colocated continuous monitor. In this paper we report the results of the model
      application to data from an unrelated monitoring site (New Hampshire, 476 m MSL)
      with poor correlation between the passive sampling and continuous monitoring (R2
      = 0.24). In addition, as opposed to the previous work, we provide comparisons of
      the frequency distributions of the hourly O3 concentrations obtained by the
      simulation and the actual continuous monitoring. In spite of the major difference
      in the R2 values, at both sites the simulation provided very satisfactory results
      within the 95% confidence interval, suggesting its broad applicability. The final
      objective of this overall approach is to develop a generic model that can
      simulate reasonably well the occurrences of ambient O3 concentrations that are
      dependent upon the elevation of the measurement site and the synoptic and local
      meteorology. Such an effort would extend the relative utility of the passive
      sampling data in explaining stochastic plant responses.

PMID- 12805856
TI  - Founding editorial: embryology--an integrated approach.
AB  - We introduce the Embryology domain of TheScientificWorld and outline the scope
      and aims. We argue for an interdisciplinary approach to problems in develop
      mental biology. Three areas are identified as being of particular relevance to
      this domain: evolutionary developmental biology, teratology, and descriptive or
      experimental embryology.

PMID- 12805857
TI  - Founding editorial--forensics and TheScientificWorld.
AB  - At the beginning of a new millennium it seems a good idea to stop for a moment
      and take stock of the current state of forensic science. As a field of scientific
      research and scientific application, forensic science is a little more than a
      century old. Forensic science may be said to have begun in 1887 with the
      simultaneous publication of A. Conan Doyle's A Study in Scarlet and Hans Gross's
      Handbuch f1/4r Untersuchungsrichter. Conan Doyle's novel introduced to the world
      the character of Sherlock Holmes, whose literary career would popularize the use
      of physical evidence in criminal investigations. Gross's manual for examining
      magistrates suggests ways in which the expertise of chemists, biologists,
      geologists, and other natural scientists could contribute to investigations.
      Gross's book was translated into a number of languages and went through various
      updated editions during the course of the century. The intervening century saw
      the development and application of fingerprinting, firearm and tool mark
      identification, forensic chemistry, forensic biology, forensic toxicology,
      forensic odontology, forensic pathology, and forensic engineering. Increasingly,
      the judicial systems of the industrial nations of the world have come to rely
      upon the expertise of scientists in a variety of disciplines. In most advanced
      countries, virtually all criminal prosecutions now involve the presentation of
      scientific testimony. This has had the beneficial effect of diminishing the
      reliance of courts on eyewitness testimony and defendant confessions.

PMID- 12805858
TI  - Trapping of organochlorine compounds in high mountain lakes.
AB  - High mountain areas have recently been observed to be polluted by organochlorine
      compounds (OC) despite their isolation. These persistent pollutants arrive at
      these remote regions through atmospheric transport. However, the mechanisms
      involving the accumulation of these compounds from the atmospheric pool to the
      lacustrine systems still need to be elucidated. These mechanisms must be related
      to the processes involving the transfer of these pollutant from low to high
      latitudes as described in the global distillation effect.

PMID- 12805859
TI  - Techniques of ozone monitoring in a mountain forest region: passive and
      continuous sampling, vertical and canopy profiles.
AB  - Ozone is the most harmful air pollutant for plant ecosystems in the Mediterranean
      and Alpine areas due to its biological and economic damage to crops and forests.
      In order to evaluate the relation between ozone exposure and vegetation injury
      under on-field conditions, suitable ozone monitoring techniques were
      investigated. In the framework of a 5-year research project aimed at ozone risk
      assessment on forests, both continuous analysers and passive samplers were
      employed during the summer seasons (1994-1998) in different sites of a wide
      mountain region (80 x 40 km2) on the southern slope of the European Alps.
      Continuous analysers allowed the recording of ozone hourly concentration means
      necessary both to calculate specific exposure indexes (such as AOT, SUM, W126)
      and to record daily time-courses. Passive samplers, even though supplied only
      weekly mean concentration values, made it possible to estimate the altitude
      concentration gradient useful to correct the altitude dependence of ozone
      concentrations to be inserted into exposure indexes. In-canopy ozone profiles
      were also determined by placing passive samplers at different heights inside the
      forest canopy. Vertical ozone soundings by means of tethered balloons (kytoons)
      allowed the measurement of the vertical concentration gradient above the forest
      canopy. They also revealed ozone reservoirs aloft and were useful to explain the
      ozone advection dynamic in mountain slopes where ground measurement proved to be
      inadequate. An intercomparison between passive (PASSAM, CH) and continuous
      measurements highlighted the necessity to accurately standardize all the exposure
      operations, particularly the pre- and postexposure conservation at cold
      temperature to avoid dye (DPE) activity. Advantages and disadvantages from each
      mentioned technique are discussed.

PMID- 12805863
TI  - Effect of winter cover crops on soil nitrogen availability, corn yield, and
      nitrate leaching.
AB  - Biculture of nonlegumes and legumes could serve as cover crops for increasing
      main crop yield, while reducing NO3 leaching. This study, conducted from 1994 to
      1999, determined the effect of monocultured cereal rye (Secale cereale L.),
      annual ryegrass (Lolium multiflorum), and hairy vetch (Vicia villosa), and
      bicultured rye/vetch and ryegrass/vetch on N availability in soil, corn (Zea mays
      L.) yield, and NO3-N leaching in a silt loam soil. The field had been in corn and
      cover crop rotation since 1987. In addition to the cover crop treatments, there
      were four N fertilizer rates (0, 67, 134, and 201 kg N ha(-1), referred to as N0,
      N1, N2, and N3, respectively) applied to corn. The experiment was a randomized
      split-block design with three replications for each treatment. Lysimeters were
      installed in 1987 at 0.75 m below the soil surface for leachate collection for
      the N 0, N 2, and N 3 treatments. The result showed that vetch monoculture had
      the most influence on soil N availability and corn yield, followed by the
      bicultures. Rye or ryegrass monoculture had either no effect or an adverse effect
      on corn yield and soil N availability. Leachate NO3-N concentration was highest
      where vetch cover crop was planted regardless of N rates, which suggests that N
      mineralization of vetch N continued well into the fall and winter. Leachate NO3-N
      concentration increased with increasing N fertilizer rates and exceeded the U.S.
      Environmental Protection Agency's drinking water standard of 10 mg N l(-1) even
      at recommended N rate for corn in this region (coastal Pacific Northwest). In
      comparisons of the average NO3-N concentration during the period of high N
      leaching, monocultured rye and ryegrass or bicultured rye/vetch and
      ryegrass/vetch very effectively decreased N leaching in 1998 with dry fall
      weather. The amount of N available for leaching (determined based on the
      presidedress nitrate test, the amount of N fertilizer applied, and N uptake)
      correlated well with average NO3-N during the high N leaching period for vetch
      cover crop treatment and for the control without the cover crops. The
      correlation, however, failed for other cover crops largely because of variable
      effectiveness of the cover crops in reducing NO3 leaching during the 5 years of
      this study. Further research is needed to determine if relay cover crops planted
      into standing summer crops is a more appropriate approach than fall seeding in
      this region to gain sufficient growth of the cover crop by fall. Testing with
      other main crops that have earlier harvest dates than corn is also needed to
      further validate the effectiveness of the bicultures to increase soil N
      availability while protecting the water quality.

PMID- 12805864
TI  - Nitrogen interactions with phosphorus and potassium for optimum crop yield,
      nitrogen use effectiveness, and environmental stewardship.
AB  - The development of best management practices (BMPs) for optimum nitrogen (N) use
      by crops contributes to farm profitability, increased food and fiber production,
      and best stewardship of the environment and its resources. Such BMPs are both
      site- and crop-specific. Optimum N use by plants is influenced not only by
      climate and certain soil characteristics, but also by management practices such
      as tillage, time and method of N application, or positive interactions with
      nutrients and supporting cropping practices. Phosphorus (P) and potassium (K) are
      two of the nutrients essential for effective use of N by plants. Nitrogen
      interactions with P and/or K help to improve root system development, dry matter
      production, and other plant functions regulating crop yield and quality.

PMID- 12805865
TI  - Best management practices for minimizing nitrate leaching from container-grown
      nurseries.
AB  - Containerized plant production represents an extremely intensive agricultural
      practice; 40,000 to 300,000 containers may occupy one acre of surface area to
      which a large amount of chemical fertilizer is applied. Currently, recommended
      fertilizer application rates for the production of containerized nursery
      ornamental plants are in excess of plant requirements, and up to 50% of the
      applied fertilizers may run off or be leached from containers. Among the
      nutrients leached or allowed to runoff, nitrogen (N) is the most abundant and is
      of major concern as the source of ground and surface water pollution. In this
      report, current N fertilizer application rates for different container-grown
      nursery ornamental plants, the amount of nitrate leaching or runoff from
      containers, and the potential for nitrate contamination of ground and surface
      water are discussed. In contrast, our best N management practices include: (1)
      applying fertilizers based on plant species need; (2) improving potting medium's
      nutrient holding capacity using obscure mineral additives; (3) using controlled
      release fertilizers; and (4) implementing zero runoff irrigation or fertigation
      delivery systems that significantly reduce nitrate leaching or runoff in
      containerized plant production and encourage dramatic changes in N management.

PMID- 12805867
TI  - Controlled release urea as a nitrogen source for spring wheat in Western Canada:
      yield, grain N content, and N use efficiency.
AB  - Controlled release nitrogen (N) fertilizers have been commonly used in
      horticultural applications such as turf grasses and container-grown woody
      perennials. Agrium, a major N manufacturer in North and South America, is
      developing a low-cost controlled release urea (CRU) product for use in field
      crops such as grain corn, canola, wheat, and other small grain cereals. From 1998
      to 2000, 11 field trials were conducted across western Canada to determine if
      seed-placed CRU could maintain crop yields and increase grain N and N use
      efficiency when compared to the practice of side-banding of urea N fertilizer.
      CRU was designed to release timely and adequate, but not excessive, amounts of N
      to the crop. Crop uptake of N from seed-placed CRU was sufficient to provide
      yields similar to those of side-banded urea N. Grain N concentrations of the CRU
      treatments were higher, on average, than those from side-banded urea, resulting
      in 4.2% higher N use efficiency across the entire N application range from 25 to
      100 kg ha(-1). Higher levels of removal of N in grain from CRU compared to side
      banded urea can result in less residual N remaining in the soil, and limit the
      possibility of N losses due to denitrification and leaching.

PMID- 12805866
TI  - The influence of mineral fertilizer combined with a nitrification inhibitor on
      microbial populations and activities in calcareous Uzbekistanian soil under
      cotton cultivation.
AB  - Application of fertilizers combined with nitrification inhibitors affects soil
      microbial biomass and activity. The objective of this research was to determine
      the effects of fertilizer application combined with the nitrification inhibitor
      potassium oxalate (PO) on soil microbial population and activities in nitrogen
      poor soil under cotton cultivation in Uzbekistan. Fertilizer treatments were N as
      urea, P as ammophos, and K as potassium chloride. The nitrification inhibitor PO
      was added to urea and ammophos at the rate of 2%. Three treatments--N200 P140 K60
      (T1), N200 PO P140 K60 (T2), and N200 P140 PO K60 (T3) mg kg(-1) soil--were
      applied for this study. The control (C) was without fertilizer and PO. The
      populations of oligotrophic bacteria, ammonifying bacteria, nitrifying bacteria,
      denitrifying bacteria, mineral assimilating bacteria, oligonitrophilic bacteria,
      and bacteria group Azotobacter were determined by the most probable number
      method. The treatments T2 and T3 increased the number of oligonitrophilic
      bacteria and utilization mineral forms of nitrogen on the background of reducing
      number of ammonifying bacteria. T2 and T3 also decreased the number of nitrifying
      bacteria, denitrifying bacteria, and net nitrification. In conclusion, our
      experiments showed that PO combined with mineral fertilizer is one of the most
      promising compounds for inhibiting nitrification rate, which was reflected in the
      increased availability and efficiency of fertilizer nitrogen to the cotton
      plants. PO combined with mineral fertilizer has no negative effects on nitrogen
      fixing bacteria Azotobacter and oligo-nitrophilic bacteria.

PMID- 12805868
TI  - Water table management reduces tile nitrate loss in continuous corn and in a
      soybean-corn rotation.
AB  - Water table management systems can be designed to alleviate soil water excesses
      and deficits, as well as reduce nitrate leaching losses in tile discharge. With
      this in mind, a standard tile drainage (DR) system was compared over 8 years
      (1991 to 1999) to a controlled tile drainage/subirrigation (CDS) system on a low
      slope (0.05 to 0.1%) Brookston clay loam soil (Typic Argiaquoll) in southwestern
      Ontario, Canada. In the CDS system, tile discharge was controlled to prevent
      excessive drainage, and water was pumped back up the tile lines (subirrigation)
      to replenish the crop root zone during water deficit periods. In the first phase
      of the study (1991 to 1994), continuous corn (Zea mays, L.) was grown with annual
      nitrogen (N) fertilizer inputs as per local soil test recommendations. In the
      second phase (1995 to 1999), a soybean (Glycine max L., Merr.)-corn rotation was
      used with N fertilizer added only during the two corn years. In Phase 1 when
      continuous corn was grown, CDS reduced total tile discharge by 26% and total
      nitrate loss in tile discharge by 55%, compared to DR. In addition, the 4-year
      flow weighted mean (FWM) nitrate concentration in tile discharge exceeded the
      Canadian drinking water guideline (10 mg N l(-1)) under DR (11.4 mg N l(-1)), but
      not under CDS (7.0 mg N l(-1)). In Phase 2 during the soybean-corn rotation, CDS
      reduced total tile discharge by 38% and total nitrate loss in tile discharge by
      66%, relative to DR. The 4-year FWM nitrate concentration during Phase 2 in tile
      discharge was below the drinking water guideline for both DR (7.3 mg N l(-1)) and
      CDS (4.0 mg N l(-1)). During both phases of the experiment, the CDS treatment
      caused only minor increases in nitrate loss in surface runoff relative to DR.
      Hence CDS decreased FWM nitrate concentrations, total drainage water loss, and
      total nitrate loss in tile discharge relative to DR. In addition, soybean-corn
      rotation reduced FWM nitrate concentrations and total nitrate loss in tile
      discharge relative to continuous corn. CDS and crop rotations with reduced N
      fertilizer inputs can thus improve the quality of tile discharge water
      substantially.

PMID- 12805869
TI  - Nitrogen fertilizer rate and crop management effects on nitrate leaching from an
      agricultural field in central Pennsylvania.
AB  - Eighteen pan lysimeters were installed at a depth of 1.2 m in a Hagerstown silt
      loam soil in a corn field in central Pennsylvania in 1988. In 1995, wick
      lysimeters were also installed at 1.2 m depth in the same access pits. Treatments
      have included N fertilizer rates, use of manure, crop rotation (continuous corn,
      corn-soybean, alfalfa-corn), and tillage (chisel plow-disk, no-till). The
      leachate data were used to evaluate a number of nitrate leaching models. Some of
      the highlights of the 11 years of results include the following: 1) growing corn
      without organic N inputs at the economic optimum N rate (EON) resulted in NO3--N
      concentrations of 15 to 20 mg l(-1) in leachate; 2) use of manure or previous
      alfalfa crop as partial source of N also resulted in 15 to 20 mg l(-1) of NO3--N
      in leachate below corn at EON; 3) NO3--N concentration in leachate below alfalfa
      was approximately 4 mg l(-1); 4) NO3--N concentration in leachate below soybeans
      following corn was influenced by fertilizer N rate applied to corn; 5) the mass
      of NO3--N leached below corn at the EON rate averaged 90 kg N ha(-1) (approx. 40%
      of fertilizer N applied at EON); 6) wick lysimeters collected approximately 100%
      of leachate vs. 40-50% collected by pan lysimeters. Coefficients of variation of
      the collected leachate volumes for both lysimeter types were similar; 7) tillage
      did not markedly affect nitrate leaching losses; 8) tested leaching models could
      accurately predict leachate volumes and could be calibrated to match nitrate
      leaching losses in calibration years, but only one model (SOILN) accurately
      predicted nitrate leaching losses in the majority of validation treatment years.
      Apparent problems with tested models: there was difficulty estimating sizes of
      organic N pools and their transformation rates, and the models either did not
      include a macropore flow component or did not handle macropore flow well.

PMID- 12805870
TI  - Nitrate relationships between stream baseflow, well water, and land use in the
      Tomorrow-Waupaca Watershed.
AB  - We examined the use of stream baseflow water quality as a representative measure
      of mean ground water quality in the Tomorrow-Waupaca Watershed in central
      Wisconsin and the relationship between agricultural land use and watershed water
      quality. From 1997 to 1999, 38 stream sites were sampled for nitrate during
      winter and summer baseflow conditions. Some sites have been sampled during winter
      baseflow conditions since 1994. The land area contributing ground water to each
      stream sampling site was delineated, resulting in 38 sub-basins. In addition,
      over 3500 test results from private wells in the watershed were compiled and
      mapped using a Geographic Information System (GIS). Nitrate concentrations in
      stream baseflow and well waters were found to have strong positive correlation in
      the sub-basins of second order or higher. This indicates that stream baseflow may
      be valid for monitoring mean ground water quality in watersheds predominantly fed
      by ground water, where much of the stream nitrate is believed to originate from
      ground water. Analysis of seasonal variation in the stream data showed that
      winter nitrate concentrations were higher than summer concentrations, implying
      that winter stream monitoring may be more critical for the assessment of overall
      ground water quality in the watershed. We also found that, as the amount of
      agricultural land increased in each sub-basin, average nitrate concentrations in
      the well and stream waters also increased, suggesting a connection between
      agricultural land use and nitrate contamination of water resources in the
      watershed.

PMID- 12805871
TI  - A new approach to determine the total airborne N input into the soil/plant system
      using 15N isotope dilution (ITNI): results for agricultural areas in Central
      Germany.
AB  - The atmospheric deposition of nitrogen (N) in the environment is of great concern
      due to its impact on natural ecosystems including affecting vegetation, reducing
      biodiversity, increasing tree growth in forests, and the eutrophication of
      aquatic systems. Taking into account the average annual N emission into the
      atmosphere in Germany of about 2 million t N (ammonia/ammonium, NOx), and
      assuming homogeneous distribution throughout Germany, an average N deposition of
      45 kg/ha x year can be calculated. Such high atmospheric N deposition could be
      confirmed by N balances from long-term field experiments in Central Germany
      (e.g., the Static Fertilization Experiment in Bad Lauchstdt). By contrast,
      estimates by standard methods indicate a deposition of only about 30 kg N/ha x
      year. This is because the standard methods are using wet-only or bulk collectors,
      which fail to take into account gaseous deposition and the direct uptake of
      atmospheric N by aerial plant parts. Therefore, a new system was developed using
      15N isotope dilution methodology to measure the actual total atmospheric N input
      into a soil/plant system (Integrated Total Nitrogen Input, ITNI). A soil/plant
      system is labeled with [15N]ammonium-[15N]nitrate and the total input of airborne
      N is calculated from the dilution of this tracer by N from the atmosphere. An
      average annual deposition of 64 +/- 11 kg/ha x year from 1994-2000 was measured
      with the ITNI system at the Bad Lauchstdt research farm in the dry belt of
      Central Germany. Measurements in 1999/2000 at three other sites in Central
      Germany produced deposition rates of about 60 kg/ha x year. These data clearly
      show that the total atmospheric N deposition into the soil/plant system
      determined by the newly developed ITNI system significantly exceeds that obtained
      from standard wet-only and bulk collectors. The higher atmospheric N depositions
      found closely match those postulated from the N balances of long-term
      agricultural field experiments.

PMID- 12805872
TI  - Class I areas at risk: event-based nitrogen deposition to a high-elevation,
      western site.
AB  - Between June 1, 2000 and September 30, 2000, 32 precipitation events were sampled
      near Telluride, CO at an elevation of 3200 m. The wet deposition site was
      operated following protocols of the Atmospheric Integrated Research Monitoring
      Network (AIRMoN), a network of the National Atmospheric Deposition Network
      (NADP). Inorganic nitrogen deposition at the Telluride site of 1.41 kg ha(-1)
      during the study period was 25 to 50% higher than nearby NADP sites. In turn,
      nitrogen deposition at these NADP sites was similar to high-elevation sites in
      and near the Colorado Front Range that have been shown to be impacted by
      atmospheric deposition of inorganic nitrogen in wetfall. Power plant emissions
      are a likely source of a major portion of this elevated inorganic nitrogen in
      wetfall to the San Juan Mountains. Principal component analysis (PCA) shows that
      solutes formed by gases that are emitted from power plants were clustered tightly
      together, including nitrate, ammonium, sulfate, and chloride. Trajectory
      analysis, including both backward and forward trajectories, shows that the air
      masses that contributed to the precipitation events with high amounts of nitrogen
      deposition at the Telluride site passed directly over or near power plants. Our
      results suggest that Class I Wilderness Areas in and near the San Juan Mountains
      are at risk to ecosystem impairment at present rates of atmospheric deposition of
      inorganic nitrogen in wetfall. Deployment of proposed power plants to this area
      will likely increase the risk of degradation of resource values in nearby Class I
      areas. While these data were collected over a short time span, they indicate that
      establishment of an official AIRMoN site in the southwestern U.S. may be
      warranted.

PMID- 12805873
TI  - The dynamics of nitrous oxide emission from the use of mineral fertilizers in
      Russia.
AB  - The intensity of nitrous oxide (N2O) emission was considered based on literature
      data on the single input of mineral N (nitrogen) fertilizers into different
      agricultural soil types in Russia. Ambient environmental factors exert a combined
      effect on the process of gaseous nitrogen formation from fertilizers applied. To
      reduce the uncertainty of estimates as much as possible, only experimental
      results obtained under conditions similar to natural were selected for the
      assessments. Mineral nitric fertilizers were applied to soil at a rate of 40 to
      75 kg/ha and the N2O emissions were measured for approximately 140 days. Daily
      average emission values varied from 0.08 to 0.45% of fertilizer nitrogen.
      Correspondingly, 1.26 and 2.38% of fertilizer nitrogen were emitted as N2O from
      chernozems and soddy podzols. In 1990, the use of fertilizers in Russian
      agricultural practices for 53 Gg N2O-N, which equates to approximately 6.1% of
      global nitrous oxide emissions from nitric fertilizers. Later, the emission
      dropped because of a decrease in the input of nitric fertilizers to agricultural
      crops, and in 1998, it constituted just 20.5% of the 1990 level. In the period
      from 2008 to 2012, the nitrous oxide emission is expected to vary from 0.5 to
      65.0 Gg N2O-N due to possible changes in national agricultural development. In
      the most likely scenario, the use of mineral fertilizers in Russia will account
      for approximately 34 to 40 Gg N2O-N emissions annually from 2008-2012.

PMID- 12805874
TI  - Airborne Ns (NO2 and NH3) in the Rijeka Bay area (Croatia), 1980-1995.
AB  - The determination of ambient levels of nitrogen dioxide (NO2) and ammonia (NH3)
      in the Rijeka Bay area started in 1980, as a part of the air quality monitoring
      programme. The results of 15 years of surveying (1980/81-1994/95) on ambient
      levels of these pollutants at two sampling sites are given in this work. Site 1
      is located in the city, opposite the old petroleum refinery facilities, while
      Site 2 is located in the settlement 25 km from the city, opposite the eastern
      industrial zone. Annual means of NO2 varied between 34 and 60 g/m3 at Site 1 and
      between 14 and 26 g/m3 at Site 2, but do not follow the 40% reduction in
      industrial emissions of this pollutant, probably due to the dominant impact of
      other minor sources, like traffic. Yearly averages of NH3 were in the range of 13
      to 26 g/m 3 at Site 1 and 7 to 16 g/m3 at Site 2, and are practically constant
      during the period studied.

PMID- 12805875
TI  - An assessment of ammonia emissions from dairy facilities in Pennsylvania.
AB  - A survey of 715 Holstein dairy farms in Pennsylvania was used to construct
      demographics for the average Holstein dairy farm. The average Holstein dairy farm
      was composed of 69 lactating cows; 11 nonlactating, pregnant cows; 44 heifers;
      and 18 calves. Milk production averaged 27.3 kg (60.0 lb). Crop area averaged
      73.6 ha. Milk production, crop area and type, average county yields, and herd
      animal groups were used to construct a typical feeding program for these farms.
      Typical rations were constructed for six feeding groups (three milk production
      groups, one nonlactating group, two heifer groups) to meet milk production,
      pregnancy, and growth requirements. Rations were constructed based on three
      forage qualities (excellent, average, and poor) typically observed on
      Pennsylvania dairy farms. Data for animal description (milk production, body
      weight, growth, and pregnancy status) and ration components and amounts consumed
      for each animal group were input into the excretion model of the Dairy Nutrient
      Planner computer program (DNP). Excretion of fecal N and dry matter (DM), urinary
      N, and total P and K were produced for each animal group and used to assess
      potential volatile losses of N. Work at the Marshak Dairy, New Bolton Center,
      indicates the majority of urinary N is rapidly lost as ammonia from dairy
      facilities. Based on this observation, the losses of N as ammonia were estimated
      to be 4.63, 4.62, and 4.28 tonne/year for the farm with excellent, average, and
      poor quality forages, respectively. Volatile losses of N may be reduced most by
      controlling levels of urea in urine. Urinary N may be reduced through dietary
      manipulation of protein and carbohydrate sources. Conversion of urea to ammonia
      may be reduced by altering the pH of barn floors and gutters. Entrapment of
      ammonia may be accomplished by acidification of manure slurry. Atmospheric
      ammonia contributes to acid rain, eutrophication of estuaries and lakes, and
      particulate air pollution. Reduction of ammonia emissions from dairy barns can
      significantly reduce atmospheric pollution and improve air and water quality.

PMID- 12805876
TI  - Nitrogen and the Baltic Sea: managing nitrogen in relation to phosphorus.
AB  - The Baltic is a large, brackish sea (4 x 10(5) km2) extending from 54N to
      approximately 66N, with a fourfold larger drainage area (population 8 x 10(7).
      Surface salinity (2 to 8 PSU) and hence biodiversity is low. In the last century,
      annual nutrient loads increased to 10(6) metric tons N and 5 x 10(4) ton P.
      Eutrophication is evident in the N-limited south, where cyanobacteria fix 2 to 4
      x 10(5) ton N each summer, Secchi depths have been halved, and O2-deficient
      bottom areas have spread. Production remains low in the P-limited north. In
      nutrient-enriched coastal areas, phytoplankton blooms, toxic at times, and
      filamentous macroalgae reduce amenity values. Loads need to be reduced of both N,
      to reduce production, and P, to limit N-fixing cyanobacterial blooms. When large
      N-load reductions have been achieved locally, algal biomass has declined. So far,
      P loads have been reduced more than N loads. If this continues, a P-limited
      Baltic proper may result, very different from previous N-limited conditions.
      Reaching the management goal of halved anthropogenic N and P loads at minimum
      cost will require better understanding of biogeochemical nutrient cycles,
      economic evaluation of proposed measures, and improved stakeholder participation.

PMID- 12805877
TI  - Genotypic effects of fertilization on seedling sweetgum biomass allocation, N
      uptake, and N use efficiency.
AB  - Screening and selecting tree genotypes that are responsive to N additions and
      that have high nutrient use efficiencies can provide better genetic material for
      short-rotation plantation establishment. A pot experiment was conducted to test
      the hypotheses that (1) sweetgum ( Liquidambar styraciflua L.) families have
      different patterns in biomass production and allocation, N uptake, and N use
      efficiency (NUE), because of their differences in growth strategies, and (2)
      sweetgum families that are more responsive to N additions will also have greater
      nutrient use efficiencies. Seedlings from two half-sib families (F10022 and
      F10023) that were known to have contrasting responses to fertility and other
      stress treatments were used for an experiment with two levels of N (0 vs. 100 kg
      N/ha equivalent) and two levels of P (0 vs. 50 kg P/ha equivalent) in a split
      plot design. Sweetgum seedlings responded to N and P treatments rapidly, with
      increases in both size and biomass production, and those responses were greater
      with F10023 than with F10022. Growth response to N application was particularly
      strong. N and P application increased the proportional allocation of biomass to
      leaves. Under increased N supply, P application increased foliar N concentration
      and content, as well as total N uptake by the seedlings. However, NUE was
      decreased by N addition and was higher in F10023 than in F10022 when P was not
      limiting. A better understanding of genotype by fertility interactions is
      important in selecting genotypes for specific site conditions and for optimizing
      nutrient use in forestry production.

PMID- 12805878
TI  - Effects of brash removal after clear felling on soil and soil-solution chemistry
      and field-layer biomass in an experimental nitrogen gradient.
AB  - Biofuels, such as brash from forest fellings, have been proposed as an
      alternative energy source. Brash removal may affect the sustainability of forest
      production, e.g., through a change in the availability of cations and N in the
      soil. We report initial effects of brash removal on inorganic N content in humus
      and mineral soil, soil-solution chemistry, and field-layer biomass after clear
      felling an N-fertilisation experiment in central Sweden. The experiment comprised
      six different fertiliser levels, ranging from 0 to 600 kg N ha(-1). Urea was
      given every 5th year during 1967 to 1982 to replicated plots, giving total doses
      of 0 to 2400 kg N ha(-1). Clear felling took place in 1995, 13 years after the
      last fertilisation. The removal of brash decreased the NO3- content in the humus
      layer after clear felling. A decrease in the NO3- concentration of the soil
      solution was indicated during most of the study period as well. No effect of the
      previous N fertilisation was found in the humus layer, but in the mineral soil
      there was an increase in NO3- content for the highest N dose after clear felling
      ( p = 0.06). The soil-solution chemistry and the field-layer biomass showed an
      irregular pattern with no consistent effects of brash removal or previous
      fertilisation.

PMID- 12805879
TI  - Factors influencing spatial variability in nitrogen processing in nitrogen
      saturated soils.
AB  - Nitrogen (N) saturation is an environmental concern for forests in the eastern
      U.S. Although several watersheds of the Fernow Experimental Forest (FEF), West
      Virginia exhibit symptoms of N saturation, many watersheds display a high degree
      of spatial variability in soil N processing. This study examined the effects of
      temperature on net N mineralization and nitrification in N-saturated soils from
      FEF, and how these effects varied between high N-processing vs. low N-processing
      soils collected from two watersheds, WS3 (fertilized with [NH4]2SO4) and WS4
      (untreated control). Samples of forest floor material (O1 horizon) and mineral
      soil (to a 5-cm depth) were taken from three subplots within each of four plots
      that represented the extremes of highest and lowest rates of net N mineralization
      and nitrification (hereafter, high N and low N, respectively) of untreated WS4
      and N-treated WS3: control/low N, control/high N, N-treated/low N, N-treated/high
      N. Forest floor material was analyzed for carbon (C), lignin, and N. Subsamples
      of mineral soil were extracted immediately with 1 N KCl and analyzed for NH4+ and
      NO3- to determine preincubation levels. Extracts were also analyzed for Mg, Ca,
      Al, and pH. To test the hypothesis that the lack of net nitrification observed in
      field incubations on the untreated/low N plot was the result of absence of
      nitrifier populations, we characterized the bacterial community involved in N
      cycling by amplification of amoA genes. Remaining soil was incubated for 28 d at
      three temperatures (10, 20, and 30 degrees C), followed by 1 N KCl extraction and
      analysis for NH4+ and NO3-. Net nitrification was essentially 100% of net N
      mineralization for all samples combined. Nitrification rates from lab incubations
      at all temperatures supported earlier observations based on field incubations. At
      30 degrees C, rates from N-treated/high N were three times those of N-treated/low
      N. Highest rates were found for untreated/high N (two times greater than those of
      N-treated/high N), whereas untreated/low N exhibited no net nitrification.
      However, soils exhibiting no net nitrification tested positive for presence of
      nitrifying bacteria, causing us to reject our initial hypothesis. We hypothesize
      that nitrifier populations in such soil are being inhibited by a combination of
      low Ca to Al ratios in mineral soil and allelopathic interactions with
      mycorrhizae of ericaceous species in the herbaceous layer.

PMID- 12805880
TI  - Seasonal changes in the character and nitrogen content of dissolved organic
      matter in an alpine/subalpine headwater catchment.
AB  - We are studying the chemical quality of dissolved organic nitrogen (DON) in a
      high-elevation watershed in the Colorado Front Range. Samples were collected over
      the 2000 snowmelt runoff season at two sites across an alpine/subalpine ecotone
      to understand how the transition between the lightly vegetated alpine and
      forested reaches of the catchment influences the chemical character of DON.
      Samples were analyzed approximately weekly for dissolved organic material (DOM)
      content and chemical character. A subset of samples was analyzed for the
      elemental content of fulvic and hydrophilic acids. Concentrations of DON at both
      sites were highest in the spring at the initiation of snowmelt, decreased during
      snowmelt, and increased again during the late summer and fall. In contrast,
      concentrations of dissolved organic carbon (DOC) peaked on the ascending limb of
      the hydrograph and declined to seasonal minima on the descending limb of the
      hydrograph. The ratio of DOC:DON showed a seasonal shift at both sites with high
      values (40 to 55) during peak runoff in early summer and lower values (15 to 25)
      during low flows late in the runoff season. These results indicate that there was
      a seasonal change in the relative N content of DOM at both sites. Chemical
      fractionation of DOC showed that there were temporal and longitudinal changes in
      the chemical character of DOC. At the alpine site, the fulvic acid content of DOC
      decreased from 57% in June to 35% in September. The change in fulvic acid was
      less pronounced at the forested site, from 66% in June to 54% in September.
      Elemental analysis of fulvic and hydrophilic acids indicated that hydrophilic
      acids were N rich compared to fulvic acids. Additionally, fulvic and hydrophilic
      acids isolated at the alpine site had a lower C:N ratio than those isolated at
      the forested site. Similarly, the C:N ratio of organic acids at both sites was
      lower in September than in June during peak runoff. These differences appear to
      be a result of changes in both DOM precursor material and hydrologic flowpaths.
      Using C:N ratios of fulvic and hydrophilic acids, we estimate that nonhumic
      material carried between 54 to 73% of the organic N in surface water at the
      alpine site and 44 to 58% of the organic N in surface water at the subalpine
      site.

PMID- 12805881
TI  - Estimated historical and current nitrogen balances for Illinois.
AB  - The Midwest has large riverine exports of nitrogen (N), with the largest flux per
      unit area to the Mississippi River system coming from Iowa and Illinois. We used
      historic and current data to estimate N inputs, outputs, and transformations for
      Illinois where human activity (principally agriculture and associated landscape
      drainage) have had a dominant impact. Presently, approximately 800,000 Mg of N is
      added each year as fertilizer and another 420,000 Mg is biologically fixed,
      primarily by soybean (Glycine max L. Merr.). These annual inputs are greater than
      exports in grain, which results in surplus N throughout the landscape. Rivers
      within the state export approximately 50% of this surplus N, mostly as nitrate,
      and the remainder appears to be denitrified or temporarily incorporated into the
      soil organic matter pool. The magnitude of N losses for 1880, 1910, 1950, and
      1990 are compared. Initial cultivation of the prairies released large quantities
      of N (approximately 500,000 Mg N year(-1)), and resulted in riverine N transport
      during the late 19th century that appears to have been on the same order of
      magnitude as contemporary N losses. Riverine flux was estimated to have been at a
      minimum in about 1950, due to diminished net mineralization and low fertilizer
      inputs. Residual fertilizer N from corn (Zea mays L.), biological N fixed by
      soybean, short-circuiting of soil water through artificial drainage, and
      decreased cropping-system diversity appear to be the primary sources for current
      N export.

PMID- 12805882
TI  - Use and misuse of nitrogen in agriculture: the German story.
AB  - Nitrogen (N) fertilization in agriculture has been discussed controversially in
      Germany for almost two centuries. The agronomist Carl Sprengel, who published his
      theory on the mineral nutrition of plants in 1828, advocated the use of mineral N
      fertilizers. Chemist Justus von Liebig, on the other hand, vehemently denied
      around 1850 the need for N fertilization. Although it soon became evident that
      Sprengel was right and Liebig was wrong, not much synthetic N fertilizer was used
      in German agriculture until around 1915, when the Haber-Bosch technique enabled
      the commercial production of NH3. The use of N fertilizers since then has grown,
      especially since 1950. To increase agricultural productivity, German governments
      have promoted, directly and indirectly, the use of N in crop and in animal
      production. Unfortunately, it was overlooked that N surpluses in agriculture
      increased rapidly; around 1980 they amounted yearly to more than 100 kg ha(-1).
      The extensive use of N in agriculture is causing environmental damage and is
      contributing substantially to the external costs of present agriculture. The main
      N compounds that affect the environment are N2O, NH3, and NO3. These compounds
      are considered to contribute one third to the external costs of agriculture.
      Additionally, the high rate of human intake of animal proteins and lipids has
      adversely affected the health of the country's population. Fundamental
      corrections in German farm policy appear inevitable.

PMID- 12805883
TI  - Applying nitrogen site-specifically using soil electrical conductivity maps and
      precision agriculture technology.
AB  - Soil texture varies significantly within many agricultural fields. The physical
      properties of soil, such as soil texture, have a direct effect on water holding
      capacity, cation exchange capacity, crop yield, production capability, and
      nitrogen (N) loss variations within a field. In short, mobile nutrients are used,
      lost, and stored differently as soil textures vary. A uniform application of N to
      varying soils results in a wide range of N availability to the crop. N applied in
      excess of crop usage results in a waste of the grower"s input expense, a
      potential negative effect on the environment, and in some crops a reduction of
      crop quality, yield, and harvestability. Inadequate N levels represent a lost
      opportunity for crop yield and profit. The global positioning system (GPS)
      referenced mapping of bulk soil electrical conductivity (EC) has been shown to
      serve as an effective proxy for soil texture and other soil properties. Soils
      with a high clay content conduct more electricity than coarser textured soils,
      which results in higher EC values. This paper will describe the EC mapping
      process and provide case studies of site-specific N applications based on EC
      maps. Results of these case studies suggest that N can be managed site
      specifically using a variety of management practices, including soil sampling,
      variable yield goals, and cropping history.

PMID- 12805884
TI  - Multicompartment ecosystem mass balances as a tool for understanding and managing
      the biogeochemical cycles of human ecosystems.
AB  - Nitrogen remains a ubiquitous pollutant in surface and groundwater throughout the
      United States, despite 30 years of pollution control efforts. A detailed
      multicompartment N balance for the Central Arizona-Phoenix ecosystem is used to
      illustrate how an ecosystem-level approach can be used to develop improved N
      management strategies. The N balance is used to demonstrate how nitrate in pumped
      groundwater used for crop irrigation could be used to reduce inputs of commercial
      fertilizer and decrease N leaching to aquifers. Effectively managing N pollution
      also will require an understanding of the complex factors that control the N
      balance, including targeted regulations, individual human behavior, land-use
      conversion, and other ecosystem management practices that affect the N balance.
      These sometimes countervailing factors are illustrated with several scenarios of
      wastewater treatment technology and population growth in the Phoenix area.
      Management of N eventually must be coupled to management of other elements,
      notably carbon, phosphorus, and salts. We postulate that an ecosystem framework
      for pollution management will result in strategies that are more effective,
      fairer, and less expensive than current approaches.

PMID- 12805885
TI  - Cost-effective emission abatement in europe considering interrelations in
      agriculture.
AB  - Agriculture is an important source of ammonia (NH3), which contributes to
      acidification and eutrophication, as well as emissions of the greenhouse gases
      nitrous oxide (N2O) and methane (CH4). Controlling emissions of one of these
      pollutants through application of technical measures might have an impact (either
      beneficial or adverse) on emissions of the others. These side effects are usually
      ignored in policy making. This study analyses cost-effectiveness of measures to
      reduce acidification and eutrophication as well as agricultural emissions of N2O
      and CH4 in Europe, taking into account interrelations between abatement of NH3,
      N2O, and CH4 in agriculture. The model used is based on the RAINS (Regional Air
      pollution INformation and Simulation) model for air pollution in Europe, which
      includes emissions, abatement options, and atmospheric source-receptor
      relationships for pollutants contributing to acidification and eutrophication. We
      used an optimisation model that is largely based on the RAINS model but that also
      includes emissions of N2O and CH4 from agriculture and technical measures to
      reduce these emissions. For abatement options for agricultural emissions we
      estimated side effects on other emissions. The model determines abatement
      strategies to meet restrictions on emission and/or deposition levels at the least
      cost. Cost-effective strategies to reduce acidification and eutrophication in
      Europe were analysed. We found that NH3 abatement may cause an increase in N2O
      emissions. If total agricultural N2O and CH4 emissions in Europe were not allowed
      to increase, cost-effective allocation of emission reductions over countries in
      Europe changed considerably.

PMID- 12805886
TI  - Using milk urea nitrogen to evaluate diet formulation and environmental impact on
      dairy farms.
AB  - Reducing nitrogen (N) excretion by dairy cattle is the most effective means to
      reduce N losses (runoff, volatilization, and leaching) from dairy farms. The
      objectives of this review are to examine the use of milk urea nitrogen (MUN) to
      measure N excretion and utilization efficiency in lactating dairy cows and to
      examine impacts of overfeeding N to dairy cows in the Chesapeake Bay drainage
      basin. A mathematical model was developed and evaluated with an independent
      literature data set to integrate MUN and milk composition to predict urinary and
      fecal excretion, intake, and utilization efficiency for N in lactating dairy
      cows. This model was subsequently used to develop target MUN concentrations for
      lactating dairy cattle fed according to National Research Council (NRC)
      recommendations. Target values calculated in this manner were 8 to 14 mg/dl for a
      typical lactation and were most sensitive to change in milk production and crude
      protein intake. Routine use of MUN to monitor dairy cattle diets was introduced
      to dairy farms (n = 1156) in the Chesapeake Bay watershed. Participating farmers
      (n = 454) were provided with the results of their MUN analyses and interpretive
      information monthly for a period of 6 months. The average MUN across all farms in
      the study increased in the spring, but the increase was 0.52 mg/dl lower for
      farmers receiving MUN results compared to those who did not participate in the
      program. This change indicated that participating farmers reduced N feeding
      compared to nonparticipants. Average efficiency of feed N utilization (N in milk
      / N in feed x 100) was 24.5% (SD = 4.5). On average, farmers fed 6.6% more N than
      recommended by the NRC, resulting in a 16% increase in urinary N and a 2.7%
      increase in fecal N compared to feeding to requirement. N loading to the
      Chesapeake Bay from overfeeding protein to lactating dairy cattle was estimated
      to be 7.6 million kg/year. MUN is a useful tool to measure diet adequacy and
      environmental impact from dairy farms.

PMID- 12805887
TI  - Managing ammonia emissions from dairy cows by amending slurry with alum or
      zeolite or by diet modification.
AB  - Animal agriculture is a significant source of atmospheric ammonia. Ammonia (NH3)
      volatilization represents a loss of plant available N to the farmer and a
      potential contributor to eutrophication in low-nitrogen input ecosystems. This
      research evaluated on-farm slurry treatments of alum or zeolite and compared
      three diets for lactating dairy cows in their effectiveness to reduce NH3
      emissions. NH3 emissions were compared using a group of mobile wind tunnels. The
      addition of 2.5% alum or 6.25% zeolite to barn-stored dairy slurry reduced NH3
      volatilization by 60% and 55%, respectively, compared to untreated slurry. The
      alum conserved NH3 by acidifying the slurry to below pH 5, while the zeolite
      conserved ammonia by lowering the solution-phase nitrogen through cation
      exchange. The use of alum or zeolite also reduced soluble phosphorus in the
      slurry. NH3 loss from fresh manure collected from lactating dairy cows was not
      affected by three diets containing the same level of crude protein but differing
      in forage source (orchardgrass silage vs. alfalfa silage) or neutral detergent
      fiber (NDF) content (30% vs. 35% NDF). NH3 losses from the freshly excreted
      manures occurred very rapidly and included the urea component plus some
      unidentified labile organic nitrogen sources. NH3 conservation strategies for
      fresh manures will have to be active within the first few hours after excretion
      in order to be most effective. The use of alum or zeolites as an on-farm
      amendment to dairy slurry offers the potential for significantly reducing NH3
      emissions.

PMID- 12805888
TI  - Improving nutrient efficiency as a strategy to reduce nutrient surpluses on dairy
      farms.
AB  - Dutch nutrient policy aims at reducing leaching of agricultural nutrients by
      internalizing the negative externalities associated with inefficient nutrient
      use. This is done by taxation of nitrogen and phosphate surpluses that exceed a
      hectare-based threshold of maximum-allowed surpluses. One management strategy
      farmers may use to reduce the nutrient surpluses on their farms is to improve the
      nutrient efficiency of the agricultural production process. This study employs
      Data Envelopment Analysis (DEA) to calculate nitrogen and phosphate efficiencies
      and an overall nutrient efficiency measure for a 3-year panel of 114 Dutch dairy
      farms. Subsequent analyses show the impact of both farm intensity and nutrient
      efficiency on the nitrogen and phosphate surpluses. It appears that farm
      intensity has a positive effect on efficiency, but efficiency and intensity exert
      opposite influences on nutrient surpluses. This is especially the case for
      nitrogen. The magnitude of a possible reduction of nitrogen surpluses through a
      strategy of efficiency improvement is therefore limited by the intensity of the
      farming system, unless the technology with which nutrients are used by the
      farming system can be further improved or input/output ratios will be altered.

PMID- 12805889
TI  - Evaluating nitrogen management options for reducing nitrate leaching from
      northeast U.S. pastures.
AB  - Substantial amounts of nitrate nitrogen NO3-N can leach from intensively grazed
      pasture in the northeast U.S. where there is about 30 cm of groundwater recharge,
      annually. Management options for reducing NO3-N leaching were evaluated for this
      environment using the Cornell Net Carbohydrate and Protein System Model and a
      recently developed nitrogen leaching index. Management options utilizing energy
      supplementation of grazing dairy cows could improve nitrogen efficiency within
      the cow, but would not necessarily reduce NO3-N leaching at the pasture scale if
      stocking rate was not controlled. The management option of using white clover to
      supply nitrogen to the pasture decreased NO3-N leaching, but produced less dry
      matter yield, which in turn reduced stocking rate. The economic returns of
      reducing NO3-N with these options need to be evaluated in light of milk prices
      and commodity and fertilizer nitrogen costs. At current prices and costs, the
      economic benefit from the energy supplementation options is substantial.

PMID- 12805890
TI  - Issues in system boundary definition for substance flow analysis: the case of
      nitrogen cycle management in Catalonia.
AB  - The great complexity of the nitrogen cycle, including anthropogenic
      contributions, makes it necessary to carry out local studies, which allow us to
      identify the specific cause-effect links in a particular society. Models of local
      societies that are based on methods such as Substance Flow Analysis (SFA), which
      study and characterise the performance of metabolic exchanges between human
      society and the environment, are a useful tools for directing local policy
      towards sustainable management of the nitrogen cycle. In this paper, the
      selection of geographical boundaries for SFA application is discussed. Data
      availability and accuracy, and the possibility of linking the results with
      instructions for decision making, are critical aspects for proper scale
      selection. The experience obtained in the construction of the model for Catalonia
      is used to draw attention to the difficulties found in regional studies.

PMID- 12805891
TI  - ThermoEnergy Ammonia Recovery Process for municipal and agricultural wastes.
AB  - The Ammonia Recovery Process (ARP) is an award-winning, low-cost, environmentally
      responsible method of recovering nitrogen, in the form of ammonia, from various
      dilute waste streams and converting it into concentrated ammonium sulfate. The
      ThermoEnergy Biogas System utilizes the new chemisorption-based ARP to recover
      ammonia from anaerobically digested wastes. The process provides for optimal
      biogas production and significantly reduced nitrogen levels in the treated water
      discharge. Process flows for the ammonia recovery and ThermoEnergy biogas
      processes are presented and discussed. A comparison with other techniques such as
      biological nitrogen removal is made. The ARP technology uses reversible
      chemisorption and double salt crystal precipitation to recover and concentrate
      the ammonia. The ARP technology was successfully proven in a recent large-scale
      field demonstration at New York City's Oakwood Beach Wastewater Treatment Plant,
      located on Staten Island. This project was a joint effort with Foster Wheeler
      Environmental Corporation, the Civil Engineering Research Foundation, and New
      York City Department of Environmental Protection. Independent validated plant
      data show that ARP consistently recovers up to 99.9% of the ammonia from the
      city's centrate waste stream (derived from dewatering of sewage sludge), as
      ammonium sulfate. ARP technology can reduce the nitrogen (ammonia) discharged
      daily into local bodies of water by municipalities, concentrated animal farming
      operations, and industry. Recent advances to ARP enhance its performance and
      economic competitiveness in comparison to stripping or ammonia destruction
      technologies.

PMID- 12805892
TI  - Nitrogen in the environment: sources, problems, and management.
AB  - Nitrogen (N) is applied worldwide to produce food. It is in the atmosphere, soil,
      and water and is essential to all life. N for agriculture includes fertilizer,
      biologically fixed, manure, recycled crop residue, and soil-mineralized N.
      Presently, fertilizer N is a major source of N, and animal manure N is
      inefficiently used. Potential environmental impacts of N excreted by humans are
      increasing rapidly with increasing world populations. Where needed, N must be
      efficiently used because N can be transported immense distances and transformed
      into soluble and/or gaseous forms that pollute water resources and cause
      greenhouse effects. Unfortunately, increased amounts of gaseous N enter the
      environment as N2O to cause greenhouse warming and as NH3 to shift ecological
      balances of natural ecosystems. Large amounts of N are displaced with eroding
      sediments in surface waters. Soluble N in runoff or leachate water enters
      streams, rivers, and groundwater. High-nitrate drinking water can cause
      methemoglobinemia, while nitrosamines are associated with various human cancers.
      We describe the benefits, but also how N in the wrong form or place results in
      harmful effects on humans and animals, as well as to ecological and environmental
      systems.

PMID- 12805893
TI  - NOx emission trading in a European context: discussion of the economic, legal,
      and cultural aspects.
AB  - Emission trading is a new instrument in environmental policy. It is an alien
      notion in most European countries and it is often viewed with hesitation. The
      paper discusses the economic, legal, and perhaps more importantly, the cultural
      aspects to consider when one tries to explore the prospects for trading emissions
      of NOx and other substances in Europe. Issues to be addressed are the present
      legal framework in Europe in relation to the national emission ceilings on NOx
      and other substances on the basis of relevant EU directives and UNECE protocols.
      The paper will discuss the extent to which the legal framework within the EU
      imposes constraints on the design of a national emission trading scheme, and what
      options are available to fit emission trading into that legislative structure.
      The NOx emission trading programme developed in the Netherlands will be used to
      demonstrate the various aspects in a European context.

PMID- 12805894
TI  - Economic analysis as a basis for large-scale nitrogen control decisions: reducing
      nitrogen loads to the Gulf of Mexico.
AB  - Economic analysis can be a guide to determining the level of actions taken to
      reduce nitrogen (N) losses and reduce environmental risk in a cost-effective
      manner while also allowing consideration of relative costs of controls to various
      groups. The biophysical science of N control, especially from nonpoint sources
      such as agriculture, is not certain. Widespread precise data do not exist for a
      river basin (or often even for a watershed) that couples management practices and
      other actions to reduce nonpoint N losses with specific delivery from the basin.
      The causal relationships are clouded by other factors influencing N flows, such
      as weather, temperature, and soil characteristics. Even when the science is
      certain, economic analysis has its own sets of uncertainties and simplifying
      economic assumptions. The economic analysis of the National Hypoxia Assessment
      provides an example of economic analysis based on less than complete scientific
      information that can still provide guidance to policy makers about the economic
      consequences of alternative approaches. One critical value to policy makers comes
      from bounding the economic magnitude of the consequences of alternative actions.
      Another value is the identification of impacts outside the sphere of initial
      concerns. Such analysis can successfully assess relative impacts of different
      degrees of control of N losses within the basin as well as outside the basin. It
      can demonstrate the extent to which costs of control of any one action increase
      with the intensity of application of control.

PMID- 12805895
TI  - Proposed methods and endpoints for defining and assessing adverse environmental
      impact (AEI) on fish communities/populations in Tennessee River reservoirs.
AB  - Two multimetric indices have been developed to help address fish community
      (reservoir fish assemblage index [RFAI]) and individual population quality (sport
      fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with
      characteristics similar to the index of biotic integrity (IBI) used in stream
      fish community determinations, was developed to monitor the existing condition of
      resident fish communities. The index, which incorporates standardized
      electrofishing of littoral areas and experimental gill netting for limnetic
      bottom-dwelling species, has been used to determine residential fish community
      response to various anthropogenic impacts in southeastern reservoirs. The SFI is
      a multimetric index designed to address the quality of the fishery for individual
      resident sport fish species in a particular lake or reservoir[4]. The SFI
      incorporates measures of fish population aspects and angler catch and pressure
      estimates. This paper proposes 70% of the maximum RFAI score and 10% above the
      average SFI score for individual species as "screening" endpoints for balanced
      indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for
      these indices indicate: (1) communities/populations are obviously balanced
      indigenous populations (BIP) indicating no adverse environmental impact (AEI), or
      are "screened out"; (2) communities/populations are considered to be potentially
      impacted; and (3) where the resident fish community/population should be
      considered adversely impacted. Suggestions are also made concerning how
      examination of individual metric scores can help determine the source or cause of
      the impact.

PMID- 12805896
TI  - Minimizing adverse environmental impact: how murky the waters.
AB  - The withdrawal of water from the nation's waterways to cool industrial facilities
      kills billions of adult, juvenile, and larval fish each year. U.S. Environmental
      Protection Agency (EPA) promulgation of categorical rules defining the best
      technology available to minimize adverse environmental impact (AEI) could
      standardize and improve the control of such mortality. However, in an attempt to
      avoid compliance costs, industry has seized on the statutory phrase "adverse
      environmental impact" to propose significant procedural and substantive hurdles
      and layers of uncertainty in the permitting of cooling-water intakes under the
      Clean Water Act. These include, among other things, a requirement to prove that a
      particular facility threatens the sustainability of an aquatic population as a
      prerequisite to regulation. Such claims have no foundation in science, law, or
      the English language. Any nontrivial aquatic mortality constitutes AEI, as the
      EPA and several state and federal regulatory agencies have properly acknowledged.
      The focus of scientists, lawyers, regulators, permit applicants, and other
      interested parties should not be on defining AEI, but rather on minimizing AEI,
      which requires minimization of impingement and entrainment.

PMID- 12805897
TI  - Measurement error affects risk estimates for recruitment to the Hudson River
      stock of striped bass.
AB  - We examined the consequences of ignoring the distinction between measurement
      error and natural variability in an assessment of risk to the Hudson River stock
      of striped bass posed by entrainment at the Bowline Point, Indian Point, and
      Roseton power plants. Risk was defined as the probability that recruitment of age
      1+ striped bass would decline by 80% or more, relative to the equilibrium value,
      at least once during the time periods examined (1, 5, 10, and 15 years).
      Measurement error, estimated using two abundance indices from independent beach
      seine surveys conducted on the Hudson River, accounted for 50% of the variability
      in one index and 56% of the variability in the other. If a measurement error of
      50% was ignored and all of the variability in abundance was attributed to natural
      causes, the risk that recruitment of age-1+ striped bass would decline by 80% or
      more after 15 years was 0.308 at the current level of entrainment mortality
      (11%). However, the risk decreased almost tenfold (0.032) if a measurement error
      of 50% was considered. The change in risk attributable to decreasing the
      entrainment mortality rate from 11 to 0% was very small (0.009) and similar in
      magnitude to the change in risk associated with an action proposed in Amendment
      #5 to the Interstate Fishery Management Plan for Atlantic striped bass (0.006)-
      an increase in the instantaneous fishing mortality rate from 0.33 to 0.4. The
      proposed increase in fishing mortality was not considered an adverse
      environmental impact, which suggests that potentially costly efforts to reduce
      entrainment mortality on the Hudson River stock of striped bass are not
      warranted.

PMID- 12805898
TI  - Use of equivalent loss models under Section 316(b) of the Clean Water Act.
AB  - Equivalent loss models encompass a variety of life table-based approaches that
      can be used to convert age- and life stage-specific estimates of entrainment and
      impingement loss to a common, easily understood currency. This common currency
      can be expressed in terms of numbers of individuals, yield to the fishery, or
      biomass to the ecosystem. These models have at least two key uses in the Section
      316(b) assessment process: screening for adverse environmental impact (AEI) and
      determination of environmental benefits associated with intake alternatives. This
      paper reviews the various forms of equivalent loss models, their data input
      requirements, and their assumptions and limitations. In addition, it describes
      how these models can be used as a second-level screening tool as part of the
      assessment of the potential for AEI. Given their relative simplicity and ease of
      use, equivalent loss models should prove to be an important tool in the arsenal
      of impact assessment methods for Section 316(b).

PMID- 12805899
TI  - A blueprint for the problem formulation phase of EPA-type ecological risk
      assessments for 316(b) determinations.
AB  - The difference between management objectives focused on sustainability of fish
      populations and the indigenous aquatic community, and a management objective
      focused on minimizing entrainment and impingement losses accounts for much of the
      ongoing controversy surrounding paragraph 316(b). We describe the EPA's
      ecological risk assessment framework and recommend that this framework be used to
      more effectively address differences in management objectives and structure
      paragraph 316(b) determinations. We provide a blueprint for the problem
      formulation phase of EPA-type ecological risk assessments for cooling-water
      intake structures (CWIS) at existing power plant facilities. Our management
      objectives, assessment endpoints, conceptual model, and generic analysis plan
      apply to all existing facilities. However, adapting the problem formulation
      process for a specific facility requires consideration of the permitting agency's
      guidelines and level of regulatory concern, as well as site-specific ecological
      and technical differences. The facility-specific problem formulation phase is
      designed around the hierarchy of biological levels of organization in the generic
      conceptual model and the sequence of cause-effect events and risk hypotheses
      represented by this model. Problem formulation is designed to be flexible in that
      it can be tailored for facilities where paragraph 316(b) regulatory concern is
      low or high. For some facilities, we anticipate that the assessment can be
      completed based on consideration of susceptibility alone. At the other extreme, a
      high level of regulatory concern combined with the availability of extensive
      information and consideration of costly CWIS mitigation options may result in the
      ecological risk assessment relying on analyses at all levels. Decisions on
      whether to extend the ecological risk assessment to additional levels should be
      based on whether regulatory or generator concerns merit additional analyses and
      whether available information is adequate to support such analyses. In making
      these decisions, the functional dependence between levels of analysis must be
      considered in making the transition to the analysis phase and risk estimation
      component of the ecological risk assessment. Regardless of how the generic
      analysis plan is modified to develop a facility-specific analysis plan, the
      resulting plan should be viewed as a tool for comparing representative species
      and alternative CWIS options by focusing on relative changes (i.e., proportional
      or percent changes) in various measures. The analysis plan is specifically
      designed to encourage consideration of multiple lines of evidence and to
      characterize uncertainties in each line of evidence. Multiple lines of evidence
      from different levels of analysis, obtained using both prospective and
      retrospective techniques, provide a broader perspective on the magnitude of
      potential effects and associated uncertainties and risks. The implications of the
      EPA's recent (April 2002) proposed regulations for existing facilities on the
      applicability of this blueprint are briefly considered.

PMID- 12805900
TI  - Regulation of apoptosis in African swine fever virus-infected macrophages.
AB  - A number of viruses have evolved antiapoptotic mechanisms to promote infected
      cell survival, either to ensure efficient productive viral replication or to
      promote long-term survival of virus-infected cells. Recent studies identified
      critical African swine fever virus genes involved in the complex regulation of
      ASFV-host interactions. Here we review the present knowledge of the recently
      identified ASFV genes with special attention to those which affect viral
      virulence, host range, and pathogenesis by regulating viral-induced apoptotic
      mechanisms.

PMID- 12805902
TI  - Microscopic photosensitization: a new tool to investigate the role of
      mitochondria in cell death.
AB  - Active involvement of mitochondria in cell death has been well-documented, but
      local apoptotic signaling between subsets of mitochondria has been poorly
      explored to date. Using mitochondrially localized CMXRos as a photosensitizer
      coupled to laser irradiation by confocal laser scanning microscopy, we
      demonstrate that partial irradiation of about half the mitochondria in human 143B
      TK- cells induces rapid loss of mitochondrial membrane potential (DeltaPsi(m)) in
      nonirradiated mitochondria. Cells so partially irradiated show apoptotic
      indications, including mobilization of cytochrome c and binding of annexin V
      within 2 h following irradiation. The loss of DeltaPsi(m) in nonirradiated
      mitochondria did not occur in cells photoirradiated in the absence of CMXRos.
      Increasing the proportion of irradiated mitochondria in each cell (up to about
      50%) generated a correspondingly greater percentage of cells in which
      nonirradiated mitochondria lost DeltaPsi(m) and which also showed apoptotic
      indications. Only at the highest level of irradiation (global for all
      mitochondria in one cell) were signs of necrosis evident (judged by uptake of
      propidium iodide). Because laser irradiation is specific to the subpopulation of
      mitochondria targeted, the data imply that a signal emanating from irradiated
      mitochondria is processed by their nonirradiated counterparts. We conclude that
      intermitochondrial signaling occurs in the subcellular response to induction of
      apoptosis.

PMID- 12805903
TI  - The 'relevant' stability of proteins with equilibrium intermediates.
AB  - Proteins perform many useful molecular tasks, and their biotechnological use
      continues to increase. As protein activity requires a stable native conformation,
      protein stabilisation is a major scientific and practical issue. Towards that
      end, many successful protein stabilisation strategies have been devised in recent
      years. In most cases, model proteins with a two-state folding equilibrium have
      been used to study and demonstrate protein stabilisation. Many proteins, however,
      display more complex folding equilibria where stable intermediates accumulate.
      Stabilising these proteins requires specifically stabilising the native state
      relative to the intermediates, as these are expected to lack activity. Here we
      discuss how to investigate the 'relevant' stability of proteins with equilibrium
      intermediates and propose a way to dissect the contribution of side chain
      interactions to the overall stability into the 'relevant' and 'nonrelevant'
      terms. Examples of this analysis performed on apoflavodoxin and in a single-chain
      mini antibody are presented.

PMID- 12805904
TI  - DNA-related pathways defective in human premature aging.
AB  - One of the major issues in studies on aging is the choice of biological model
      system. The human premature aging disorders represent excellent model systems for
      the study of the normal aging process, which occurs at a much earlier stage in
      life in these individuals than in normals. The patients with premature aging also
      get the age associated diseases at an early stage in life, and thus age
      associated disease can be studied as well. It is thus of great interest to
      understand the molecular pathology of these disorders.

PMID- 12805905
TI  - Isotope fractionation of toluene: a perspective to characterise microbial in situ
      degradation.
AB  - A concept to assess in situ biodegradation of organic contaminants in aquifers is
      presented. The alteration of the carbon isotope composition of contaminants along
      the groundwater flow path indicates microbial degradation processes and can be
      used as an indicator for in situ biodegradation. The Rayleigh equation was
      applied to calculate the percentage of the in situ biodegradation (B[%]) using
      the change in the isotopic composition of contaminants (Rt/R0) along the ground
      water flow path and a kinetic carbon isotope fractionation factor (alphaC)
      derived from defined biodegradation experiments in the laboratory. When the
      groundwater hydrology is known and a representative source concentration (C0) for
      a groundwater flow path can be determined, the extent of in situ biodegradation
      can be quantified.

PMID- 12805906
TI  - Monitoring of the gasoline oxygenate MTBE and BTEX compounds in groundwater in
      Catalonia (northeast Spain).
AB  - Headspace (HS) gas chromatography with flame ionisation detection (HS-GC-FID) and
      purge and trap (P) gas chromatography-mass spectrometry (P) were used for the
      determination of methyl-tert-butyl ether (MTBE) and benzene, toluene, and xylenes
      (BTEX) in groundwater. In this work, we present the first data on the levels of
      MTBE and BTEX in different groundwater wells in the area of Catalonia (northeast
      Spain). This monitoring campaign corresponded to 28 groundwater wells that were
      located near petrol service stations, oil refinery storage tanks, and/or chemical
      industry at different locations of Catalonia during the period of 1998/1999. The
      levels of MTBE detected varied between 4-300 microg/l, but two sites had MTBE
      levels up to 3 and 13 mg/l. In many cases, the BTEX levels were below 1 microg/l,
      whereas 7 sites had levels varying from 19 microg/l up to 3 mg/l. Most of them
      were related to leakage from underground tanks in petrol service stations, while
      the remaining three corresponded respectively to chemical industrial pollution of
      undetermined origin and to a leak from high-ground petrol tanks in petrochemical
      refinery factories. The aquifers involved were constituted by detritus coarse
      materials, sands, and conglomerates. Piezometric levels were roughly comprised
      between 3 and 40 m, and permeability (K) and transmissivity (T) values were
      estimated from field measurements. The MTBE/BTEX ratio was also calculated and
      reached values up to 250. These values were expected, since if we consider that
      spilled oxygenated gasoline is the source of well contamination and based on
      solubility considerations alone, the MTBE source concentrations would be about
      200 times higher than any BTEX compounds.

PMID- 12805907
TI  - Polar organic pollutants in groundwater: experimental approaches to
      biodegradation during subsoil passage.
AB  - A selection of polar organic compounds was investigated for their biodegradation
      on a laboratory scale fixed-bed bioreactor and the decline of the parent
      compounds besides the formation of metabolites was monitored. Of particular
      interest was the investigation into the degradation of pesticides, especially
      isoproturon (IPU), surfactants and industrial by-products of chemical synthesis.
      The results from the laboratory degradation experiments are compared to findings
      in groundwater.

PMID- 12805908
TI  - Genotoxicity studies in groundwater, surface waters, and contaminated soil.
AB  - It is at present considered important to include biological tests in measuring
      programmes of environmental samples to supplement the chemical and physical
      parameters that are currently used. A battery of tests is therefore necessary,
      also within a given "endpoint" (e.g., genotoxicity), because one single test will
      not give all the answers to our questions. As it is not possible to include all
      available tests in routine screening programmes, a selection of tests should be
      made. According to comparative investigations, the bacterial Ames test remains
      very important. When no preconcentration step is involved, other bacterial tests
      (e.g., the umu-C and VITOTOX tests) may be recommended. The comet assay may be
      used in Daphnia or human white blood cells. Further validations, comparisons,
      mechanistic investigations, etc. remain necessary as differences are often found
      between the tests that are not solely explained by differences in genetic
      endpoint and that therefore should further be investigated and understood.

PMID- 12805909
TI  - Environmental economics for environmental protection.
AB  - Environmental economics deals with the optimal allocation of production factors
      and correcting market failure in protecting the environment. Market failure
      occurs because of externalities, common property resources, and public goods.
      Environmental policy instruments include direct regulation, taxes/subsidies,
      tradable permits, deposit systems, voluntary agreements, and persuasion.
      Environmental policies usually focus on one pollutant or environmental issue but
      may have substantial impacts on other emissions and environmental problems.
      Neglecting these impacts will result in suboptimal policies. We present an
      integrated optimisation model for determining cost-effective strategies to
      simultaneously reduce emissions of several pollutants from several sources,
      allowing for interrelations between sources and abatement options. Our integrated
      approach in regard to acidifying compounds and greenhouse gases will be able to
      provide cost-effective policy options that will result in lower overall abatement
      costs. This paper shows that efficient emission reduction can be calculated, but
      we argue that, for transboundary air pollution and climate change, it is
      difficult to implement the socially optimal solution because strong incentives
      exist for "free-riding". In order to implement efficient policies, international
      environmental agreements like the Gothenburg or the Kyoto Protocol are necessary
      to establish stable coalitions. The stability of these agreements depends on the
      distribution of costs and benefits over countries and on the redistribution of
      the gains of cooperation.

PMID- 12805910
TI  - Marine biogenic minerals hold clues about changes in ocean chemistry and climate:
      some important lessons learned from studies of stable and radioactive isotopes of
      Be and Al.
AB  - The elements Be and Al exhibit very short residence time in ocean waters, and
      therefore serve as useful tracers for the study of biogeochemical processes in
      seawater. A unique feature of these tracers is that nuclear interactions of
      cosmic rays in the atmosphere produce appreciable amounts of two radioactive
      isotopes, 10Be (with a half-life of 1.5 my) and 26Al (with a half-life of 0.7
      my), which are introduced in the hydrosphere, cryosphere, and lithosphere via
      precipitation. Thus, these elements are labeled by their respective radioactive
      isotopes, which help quantitative tagging of their biogeochemical cycles.
      Finally, as we report here, several marine organisms incorporate them in their
      skeletal shells in certain fixed proportions to their concentrations in the
      seawater, so that it seems possible to study changes in the ocean chemistry and
      climate over the past several million years. We summarize here the recent
      discovery by Dong et al. of significant enrichments of intrinsic Be and Al in
      marine foraminiferal calcite and coral aragonite, and of Al in opal
      (radiolarians) and aragonite (corals), which should make it possible to determine
      10Be/Be and 26Al/Al in oceans in the past. We also summarize their measured
      10Be/9Be in foraminiferal calcite in Pacific Ocean cores, which reveal that the
      concentrations and ratios of the stable and cosmogenic isotopes of Be and Al have
      varied significantly in the past 30 ky. The implications of these results are
      discussed.

PMID- 12805911
TI  - Fructan biosynthetic and breakdown enzymes in dicots evolved from different
      invertases. Expression of fructan genes throughout chicory development.
AB  - Fructans are fructose-based oligo- and polymers that serve as reserve
      carbohydrates in many plant species. The biochemistry of fructan biosynthesis in
      dicots has been resolved, and the respective cDNAs have been cloned. Recent
      progress has now succeeded in elucidating the biochemistry and molecular biology
      of fructan biodegradation in chicory, an economically important species used for
      commercial inulin extraction. Unlike fructan biosynthetic genes that originated
      from vacuolar-type invertase, fructan exohydrolases (FEHs) seem to have evolved
      from a cell-wall invertase ancestor gene that later obtained a low iso-electric
      point and a vacuolar targeting signal. Expression analysis reveals that fructan
      enzymes are controlled mainly at the transcriptional level. Using chicory as a
      model system, northern analysis was consistent with enzymatic activity
      measurements and observed carbohydrate changes throughout its development.

PMID- 12805912
TI  - Mechanisms by which human cells bypass damaged bases during DNA replication after
      ultraviolet irradiation.
AB  - The replication of damaged DNA involves cascading mechanisms of increasing
      complexity but decreasing accuracy. The most accurate mechanism uses low-fidelity
      DNA polymerases, Pol H and Pol I, which have active sites sufficiently large to
      accommodate a pyrimidine dimer. Replicative bypass of DNA damage by these
      polymerases produces an accurately replicated, newly synthesized strand. Pol H
      negative cells (XP-V cell lines) either adopt a proposed secondary bypass
      mechanism or a recombinational mode. The mechanism of the secondary bypass is
      unclear, but a number of experiments suggests roles for excision repair to remove
      damage ahead of replication forks, hRad6/18 proteolysis to clear the blocked
      forks, and the Rad17-RFC and 9-1-1 complexes to establish a new replication
      apparatus. This alternative pathway requires functional p53. In Pol H negative
      cells in which p53 is also inactive, the arrested fork fragments into DNA double
      strand breaks. Foci containing PCNA, Mre11/Rad50/Nbs1, and gamma-H2Ax can then be
      detected, along with chromosomal rearrangement and high frequencies of sister
      chromatid exchanges. The recruitment of recombination components to the arrested
      forks represents the ultimate failure of replication machinery to relieve the
      arrested state and bypass the damage. The resulting chromosomal instability in
      surviving cells will contribute to malignant transformation.

PMID- 12805913
TI  - Similar motor block effects and disposition kinetics between lidocaine and (+/
      )mepivacaine in patients undergoing axillary brachial plexus block during day
      case surgery.
AB  - The aim of this investigation was to compare the clinical effects and
      pharmacokinetics of lidocaine (one metabolite) and mepivacaine (two metabolites)
      in 2 groups of 15 patients undergoing axillary brachial plexus anaesthesia. The
      study had a randomised design. The 30 patients were divided into 2 groups. The
      patients received either lidocaine (600 mg = 2.561 mMol + 5 mg ml(-1) adrenaline)
      or mepivacaine (600 mg = 2.436 mMol + 5 microg ml(-1) adrenaline), injected via
      the axilla near the brachial plexus over a period of 30 s. Onset of surgical
      analgesia was defined as the period from the end of the local anaesthetic
      injection to the loss of pinprick sensation in the distribution of the ulnar,
      radial, and median nerve. Motor block was measured. Onset of motor block was
      similar for both drugs. Lidocaine is eliminated biexponentially with a t1/2alpha
      of 9.95 +/- 14.3 min and a t1/2beta of 2.86 +/- 1.55 h. Lidocaine is metabolised
      into MEGX (tmax 2.31 +/- 0.84 h; Cmax 0.32 +/- 0.13 mg l(-1); t1/2beta 2.36 +/-
      2.35 h; total body clearance was 67.9 +/- 28.9 l h(-1)). Mepivacaine is
      eliminated rapidly and monoexponentially with a t1/2 of 4.78 +/- 2.38 h, a Cmax
      of 3.89 +/- 0.83 mg l(-1), and a tmax of 0.41 +/- 0.19 h. The total body
      clearance of mepivacaine is 50% of that of lidocaine, 26.9 +/- 10.6 l h(-1) vs.
      67.9 +/- 28.9 l h-1, respectively (p < 0.0001). (+/-)mepivacaine is metabolised
      into (+/-)4-OHmepivacaine (Cmax 0.45 +/- 0.25 mg l(-1); t1/2beta 6.48 +/- 6.57 h)
      and (+/-)2,6-pipecoloxylidide (Cmax 0.56 +/- 0.30 mg l(-1); t1/2beta 1.48 +/-
      0.74 h). For the axillary brachial plexus block, lidocaine and mepivacaine show
      similar pharmacodynamic and pharmacokinetic behaviour, despite the number of
      metabolites, and can therefore be used to the clinical preference for this
      regional anaesthetic technique.

PMID- 12805914
TI  - Attachment of histidine tags to recombinant tumor necrosis factor-alpha
      drastically changes its properties.
AB  - When studying two different histidine tags attached to the N-termini of the
      trimeric cytokine tumor necrosis factor alpha (TNF), the biological activity-
      measured as cytotoxicity on the L-929 cell line--of both tagged proteins was
      drastically reduced. The longer His10 tag reduced cytotoxicity to approximately
      16% and the shorter His7 tag to 6% of the activity of their nontagged
      counterparts. After removal of the tags, biological activities reverted to the
      expected normal values, which clearly shows the key role of the attached
      histidine tags in diminishing biological activity. Studies on the mechanism of
      these effects revealed no specific interactions and showed that even the natural
      flexible N-terminus of TNF presents a steric hindrance for receptor binding,
      while any extension of the N-terminus increases this hindrance and consequently
      reduces biological activity. Also, in other proteins, the ligand or substrate
      binding sites may be hindered by histidine tags, leading to wrong conclusions
      about biological activity or other properties of the proteins. Thus caution is
      advised when using His-tagged proteins directly in screening procedures or in
      research.

PMID- 12805915
TI  - Salinity preference in hatchery-reared juvenile red drum.
AB  - Juvenile red drum (Sciaenops ocellatus), reared in either 15- or 30-ppt salinity
      seawater, were tested to determine whether they develop preference for the
      salinity of the water in which they were cultured. In a two-choice test, large-
      and small-sized juvenile red drum chose the raceway that matched the seawater in
      which they were cultured over the other salinity. Additional large and small fish
      reared in either 15- or 30-ppt salinity water were also tested following a 4-h
      acclimation period that simulated the duration of transport time from the
      hatchery to a release site. These fish also showed preference for their original
      culture salinity. This observed salinity preference in juvenile red drum has
      implications with respect to movement or residency of hatchery-reared juvenile
      red drum out-planted into natural coastal systems.

PMID- 12805916
TI  - Innovations in the speciation of organolead compounds in water: towards a more
      rational, rapid, and simple analytical process.
AB  - Speciation analysis calls for rapid, simple systems for minimizing errors made in
      the most troublesome of all steps in the analytical process: sample preparation.
      In this context, continuous-flow systems are of great help. The evolution in the
      different methodologies enabled solutions to the main shortcomings occurring from
      the lack of selectivity of using RP-C18 as sorbent material. One solution was a
      shift to more sensitive and selective, but only partially automated, systems
      employing C60 fullerene and Grignard's reagent; another was a shift to completely
      automated systems employing sodium tetrapropylborate; and a final solution was to
      employ the simplest possible configuration by removing the reagent stream. The
      analytical methods developed allowed the identification and quantification of
      different organolead species at the pg/ml levels in rainwater samples, with
      precision (RSD) of about 5% and recoveries ranging from 92 to 100%.

PMID- 12805918
TI  - Fractionation of hepatic nonparenchymal cells.
AB  - The majority of parenchymal cells from mammalian liver cells can be removed by
      very low speed centrifugation (50 g) but a simple low-density barrier (1.096
      g/ml) is required to remove the remaining parenchymal cells from the 50-g
      supernatant which contains all of the lower density nonparenchymal cells.
      Continuous gradients of Nycodenz can provide satisfactory resolution of Kupffer,
      stellate, and endothelial cells on an analytical basis but the separation of
      different cell types is not sufficient preparatively. Flotation through a low
      density iodixanol barrier can, however, provide a satisfactory enrichment of the
      least dense nonparenchymal cell--the stellate cells.

PMID- 12805917
TI  - Kinetics of natural attenuation of BTEX: review of the critical chemical
      conditions and measurements at bore scale.
AB  - This paper describes the chemical conditions that should favour the
      biodegradation of organic pollutants. Thermodynamic considerations help to define
      the reaction that can occur under defined chemical conditions. The BTEX (benzene,
      toluene, ethylbenzene, and xylene) degradation is focused on benzene, as it is
      the most toxic oil component and also because it has the slowest degradation rate
      under most field conditions. Several studies on benzene degradation allow the
      understanding of the basic degradation mechanisms and their importance in field
      conditions. The use of models is needed to interpret field data when transport,
      retardation, and degradation occur. A detailed comparison of two existing models
      shows that the limits imposed by oxygen transport must be simulated precisely to
      reach correct plumes shapes and dimensions, and that first-order kinetic
      approaches may be misleading. This analysis led us to develop a technique to
      measure directly biodegradation in the field. The technique to recirculate water
      at the borehole scale and the CO2 analysis are depicted. First results of
      biodegradation show that this technique is able to easily detect the degradation
      of 1 mg/l of hydrocarbons and that, in oxic media, a fast degradation rate of
      mixed fuel is observed.

PMID- 12805919
TI  - Preparation of preformed iodixanol gradients.
AB  - The Protocol Article describes the strategies for the formation of preformed
      discontinuous and continuous density gradients. Most of the techniques can be
      applied to the use of any gradient solute but some of the detailed
      recommendations on continuous gradients only apply to iodixanol gradients because
      of variations in viscosity and rates of diffusion between different solute types.
      Operational variations that require consideration when dealing with specific
      types of biological particle are also dealt with at the end of this Protocol
      Article.

PMID- 12805920
TI  - Formation of self-generated gradients of iodixanol.
AB  - The formation of self-generated gradients of iodixanol from a solution of uniform
      concentration requires the use of vertical or near-vertical rotors. The density
      profile that is generated depends upon the sedimentation path length of the
      rotor, centrifugation time, RCF and temperature. Modulation of the starting
      concentration changes the density range of the gradient. This Protocol Article
      illustrates the effect of these parameters on gradient shape in a few selected
      rotors. Because the gradients are formed by the centrifugal field, they are
      highly reproducible and easy to execute.

PMID- 12805921
TI  - Immobilized native bacteria as a tool for bioremediation of soils and waters:
      implementation and modeling.
AB  - Based on 3,4-dihydroxyphenylacetate (3,4-DHPA) dioxygenase amino acid sequence
      and DNA sequence data for homologous genes, two different oligonucleotides were
      designed. These were assayed to detect 3,4-DHPA related aromatic compound
      degrading bacteria in soil samples by using the FISH method. Also, amplification
      by PCR using a set of ERIC primers was assayed for the detection of Pseudomonas
      GCH1 strain, which used in the soil bioremediation process. A model was developed
      to understand and predict the behavior of bacteria and pollutants in a
      bioremediation system, taking into account fluid dynamics, molecular/cellular
      scale processes, and biofilm formation.

PMID- 12805922
TI  - Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of
      Clavubactin and Synulox in healthy cats.
AB  - The aims of this investigation were to calculate the pharmacokinetic parameters
      and to identify parameters, based on individual plasma concentration-time curves
      of amoxicillin and clavulanic acid in cats, that may govern the observed
      differences in absorption of both drugs. The evaluation was based on the data
      from plasma concentration-time curves obtained following a single-dose, open,
      randomised, two-way crossover phase-I study, each involving 24 female cats
      treated with two Amoxi-Clav formulations (formulation A was Clavubactin and
      formulation was B Synulox; 80/20 mg, 24 animals, 48 drug administrations). Plasma
      amoxicillin and clavulanic acid concentrations were determined using validated
      bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2 =
      1.24 +/- 0.28 h, Cmax = 12.8 +/- 2.12 microg/ml), and that of clavulanic acid 0.6
      h (t1/2 = 0.63 +/- 0.16 h, Cmax = 4.60 +/- 1.68 microg/ml). There is a ninefold
      variation in the AUCt of clavulanic acid for both formulations, while the AUCt of
      amoxicillin varies by a factor of two. The highest clavulanic acid AUCt values
      indicate the best absorption; all other data indicate less absorption. Taking
      into account that the amoxicillin-to-clavulanic acid dose ratio in the two
      products tested was 4:1, the blood concentration ratios may actually vary much
      more, apparently without compromising the products" high efficacy against
      susceptible microorganisms.

PMID- 12805923
TI  - Isolation of human polymorphonuclear leukocytes (granulocytes) from a leukocyte
      rich fraction.
AB  - Human peripheral blood polymorphonuclear leukocytes (PMNs) or granulocytes from a
      leukocyte-rich plasma (LRP) are banded at an interface between two layers of
      iodixanol. If the denser layer of iodixanol is omitted the PMNs may alternatively
      be pelleted. The procedure can be adapted to blood from other species by small
      changes to the density of the two iodixanol layers. The method works optimally
      with EDTA- or citrate-anticoagulated blood.

PMID- 12805924
TI  - Purification of intact plant protoplasts by flotation at 1g.
AB  - From a standard plant tissue digest adjusted to a density of 1.07 g/ml,
      protoplasts can be harvested by flotation through a low density barrier (1.03
      g/ml). The delicate nature of these bodies is suited to this flotation strategy
      which can be carried out at 1g.

PMID- 12805925
TI  - Purification of peroxisomes using a density barrier in a swinging-bucket rotor.
AB  - In iodixanol, peroxisomes are the densest organelle in the light mitochondrial
      fraction and are therefore easily separated from the other components (lysosomes,
      mitochondria, etc.) in a preformed isosmotic continuous gradient. Because of the
      large difference in density between peroxisomes and the next densest organelle
      (mitochondria), a density barrier is effective. The resolution of the peroxisomes
      is far superior than that in sucrose and, unlike in Percoll, there is no
      contamination from endoplasmic reticulum.

PMID- 12805926
TI  - Determining arsenic distribution in urban soils: a comparison with nonurban
      soils.
AB  - There are many challenges in the determination of arsenic background
      concentrations in soils. However, these challenges are magnified when those
      determinations are carried out on urban soils. Irrespective of this, it is
      important to correctly identify and understand the extent of pollution in order
      to provide efficient preventative, remedial actions and cost-effective management
      of contaminated areas. This review paper discusses the factors that make the
      determination of arsenic background concentrations in urban areas different from
      similar determinations in nonurban areas. It also proposes solutions, where
      applicable, that are based on experience in determining arsenic background
      concentrations in both urban and nonurban areas in Florida, and from other
      studies in the literature. Urban soils are considerably different from nonurban
      areas because they have significant human disturbance, making them more difficult
      to study. They are characterized by high spatial and temporal variability,
      compaction, and modified chemical and physical characteristics. These differences
      have to be addressed during site selection, sample collection, and statistical
      analyses when determining arsenic distribution.

PMID- 12805927
TI  - Toxicity of flare and crude hydrocarbon mixtures.
AB  - The toxicity of whole, saturate, and aromatic hydrocarbon mixtures from flare pit
      and crude oil sources were evaluated using Lumbricus terrestris. Body burden
      analysis was used to analyze the intrinsic toxicity of the six hydrocarbon
      mixtures. The major fractions of the whole mixtures, the saturate, and aromatic
      fractions had different intrinsic toxicities; the aromatics were more toxic than
      the saturates. The toxicity of the saturate and aromatic fractions also differed
      between the mixtures. The flare saturate mixture was more toxic than the crude
      saturate mixture, while the crude aromatic mixture was more toxic than the flare
      aromatic mixture. The most dramatic difference in toxicity of the two sources was
      between the flare whole and crude whole mixtures. The crude whole mixture was
      very toxic; the toxicity of this mixture reflected the toxicity of the crude
      aromatic fraction. However, the flare whole mixture was not toxic, due to a lack
      of partitioning from the whole mixture into the lipid membrane of the exposed
      worms. This lack of partitioning appears to be related to the relatively high
      concentrations of asphaltenes and polar compounds in the flare pit whole mixture.

PMID- 12805928
TI  - 8-Chloro-cAMP-related changes on mice uteri.
AB  - Histopathological effects of cAMP analog (8-Chloro-cAMP), tamoxifen, and
      medroxyprogesterone, alone or combined, upon BALB/c mice uteri are reported. 8
      Chloro-cAMP diminished uterine weight, but did not modify its histopathology or
      estral cycle significantly. Tamoxifen diminished uterine weight showing cystic
      hyperplasia and an estral cycle arrested at diestrus. Medroxyprogesterone
      increased uterine weight, caused a swelling of the endometrium and a
      pseudopregnancy estrus. When combined with 8-Chloro-cAMP, tamoxifen or
      medroxyprogesterone always had a predominant effect. We concluded that the
      effects of 8-Chloro-cAMP on mice uteri did not cause significant changes on its
      histopathology, but diminished its weight.

PMID- 12805930
TI  - OptiPrep density gradient solutions for mammalian organelles.
AB  - Any density gradient for the isolation of mammalian organelles should ideally
      only expose the sedimenting biological particles to an increasing concentration
      of the gradient solute. Thus they will experience only an increasing density and
      viscosity, other parameters such as osmolality, pH, ionic strength and the
      concentration of important additives (such as EDTA and DTT) should remain as
      close to constant as possible. This Protocol Article describes the strategies for
      the dilution of OptiPrep in order to prepare such solutions for mammalian
      organelles and membranes.

PMID- 12805929
TI  - Fractionation of Golgi, endoplasmic reticulum, and plasma membrane from cultured
      cells in a preformed continuous iodixanol gradient.
AB  - A continuous iodixanol gradient within the range 0-30% (w/v) iodixanol can
      resolve the major membrane compartments of the endoplasmic reticulum, Golgi
      membranes, and plasma membrane from a postnuclear supernatant prepared from a
      cultured cell homogenate. The precise density range of the gradient and the
      centrifugation conditions (100,000-200,000 g for 2-16 h) vary with the type of
      cell and the requirements of the separation. The strategy is widely used to study
      the processing of proteins within cells.

PMID- 12805931
TI  - OptiPrep density gradient solutions for nonmammalian organelles.
AB  - Any density gradient for the isolation of nonmammalian organelles should ideally
      only expose the sedimenting biological particles to an increasing concentration
      of the gradient solute. Thus they will experience only an increasing density and
      viscosity, other parameters such as osmolality, pH, ionic strength and the
      concentration of important additives (such as EDTA and DTT) should remain as
      close to constant as possible. This Protocol Article describes the strategies for
      the dilution of OptiPrep in order to prepare such solutions for organelles and
      membranes from nonmammalian sources such as yeast.

PMID- 12805932
TI  - Periphyton function in lake ecosystems.
AB  - Periphyton communities have received relatively little attention in lake
      ecosystems. However, evidence is increasing that they play a key role in primary
      productivity, nutrient cycling, and food web interactions. This review summarizes
      those findings and places them in a conceptual framework to evaluate the
      functional importance of periphyton in lakes. The role of periphyton is
      conceptualized based on a spatial hierarchy. At the coarsest scale, landscape
      properties such as lake morphometry, influence the amount of available habitat
      for periphyton growth. Watershed-related properties, such as loading of dissolved
      organic matter, nutrients, and sediments influence light availability and hence
      periphyton productivity. At the finer scale of within the lake, both habitat
      availability and habitat type affect periphyton growth and abundance. In
      addition, periphyton and phytoplankton compete for available resources at the
      within-lake scale. Our review indicates that periphyton plays an important
      functional role in lake nutrient cycles and food webs, especially under such
      conditions as relatively shallow depths, nutrient-poor conditions, or high water
      column transparency. We recommend more studies assessing periphyton function
      across a spectrum of lake morphometry and trophic conditions.

PMID- 12805933
TI  - Sarco(endo)plasmic reticulum Ca2+-ATPase-2 gene: structure and transcriptional
      regulation of the human gene.
AB  - The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of
      active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this
      study, we describe the complete structure of the human SERCA2 gene and its 5 
      regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in
      Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20
      introns. The last two exons of the pre-mRNA produce by alternatively splicing the
      cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b
      isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2
      genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse
      species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1
      binding sites, and a thyroid hormone responsive element (TRE). There are two
      other conserved regulatory regions located between positions -410 to -661 bp and
      from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory
      regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF
      1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb,
      there is no significant homology among the SERCA2 genes cloned. In addition, the
      human gene has several repeated sequences mainly of the Alu and L2 type located
      upstream from position -1.7 kb, spanning in a continuous fashion for more than 40
      kb. In this study, we report the cloning of 2.4 kb of 5-regulatory region and
      demonstrate that the proximal promoter region is sufficient for expression in
      cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA
      elements which down-regulate the expression of the SERCA2 gene in neonatal
      cardiomyocytes.

PMID- 12805934
TI  - Calcitonin gene-related peptide (CGRP) in cerebrovascular disease.
AB  - Cerebral blood vessels are innervated by sensory nerves that store several
      neurotransmitters among which calcitonin gene-related peptide (CGRP) is the most
      abundant. In primary headaches, there is a clear association between the head
      pain and the release of CGRP. In cluster headache there is an additional release
      of vasoactive intestinal peptide (VIP). In connection with administration of
      triptans, the headache subsides and the neuropeptide release normalises, in part
      via a presynaptic effect. In subarachnoid hemorrhage (SAH), CGRP is released to
      counterbalance the blood-induced vasospasm. In severe cases, the stored CGRP may
      be exhausted while infusion of CGRP may limit cerebral vasospasm. Thus,
      interactions with the trigeminovascular system at CGRP receptors may be a useful
      target for understanding of cerebrovascular disease and to design novel
      treatments.

PMID- 12805936
TI  - Biodegradation of chlorsulfuron and metsulfuron-methyl by Aspergillus niger.
AB  - In this work, investigations were performed under laboratory conditions of the
      degradation ability by a common soil fungus, Aspergillus niger, toward
      chlorsulfuron and metsulfuron-methyl. The results were very encouraging (79% for
      chlorsulfuron and 61% for metsulfuron-methyl of total degradation), especially
      compared to those registered in our previous studies with a Pseudomonas
      fluorescens strain B2 (about 21 to 32%). Furthermore, the chemical degradation of
      the two compounds was studied and two products (1[2-methoxy-benzene-1-sulfonyl]-7
      acetyltriuret and 1[2-chlorobenzene-1-sulfonyl]-7-acetyltriuret) were isolated
      and characterised by hydrolysis in acidic conditions. Our aim in the future will
      be the identification of intermediate metabolites by HPLC and LC-MS analyses in
      order to identify the degradative pathway by the fungal strain and to compare
      this to those obtained by chemical degradation and by P. fluorescens strain.

PMID- 12805935
TI  - Enhanced hepatocarcinogenicity due to agonists of peroxisome proliferator
      activated receptors in senescent rats: role of peroxisome proliferation, cell
      proliferation, and apoptosis.
AB  - Exposure to agonists of peroxisome proliferator-activated receptor alpha
      (PPARalpha) causes liver cancer in rodents, with aged animals being more
      susceptible than their younger counterparts to this effect. Treatment with these
      chemicals produced a five- to sevenfold higher yield of grossly visible hepatic
      tumors in old rats compared to young animals. The enhanced susceptibility of the
      aged livers to the carcinogenic effect of PPAR agonists could not be explained by
      differences in levels of peroxisomal and/or cell proliferation between young and
      old animals, as neither of these responses was exaggerated with aging. Reported
      studies have shown that activating PPARalpha results in the suppression of
      hepatic apoptosis. This effect is expected to diminish the ability of the liver
      to purge itself of pre-existing neoplastic cells, allowing them to progress to
      tumors. New findings from our laboratories show that the aged liver is
      exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition,
      aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2
      than livers of young, adult, and middle-aged animals. Interestingly, the
      PPARalpha agonist Wy-14,643 significantly diminished elements of the proapoptotic
      machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably
      increasing elements of this machinery in younger animals. Taken together, while
      activation of PPARs appears to inhibit apoptosis in livers of senescent animals,
      activating these receptors seems to stimulate the apoptotic machinery in young
      animals. This paradoxical effect may be responsible for the exaggerated
      sensitivity of the aged liver to the carcinogenic effect of agents that activate
      PPARs.

PMID- 12805937
TI  - Recent levels of technetium-99 in seawater at the west coast of Svalbard.
AB  - Seawater from the western coast of Svalbard was sampled in the spring and summer
      of 2000 to determine levels of technetium-99 (99Tc), a conservative-behaving,
      manmade radionuclide originating from European nuclear reprocessing plants. This
      paper deals with the recent levels of this radionuclide in seawater and with the
      link between an Arctic fjord, Kongsfjorden, and the Western Spitsbergen Current
      (WSC), investigated using 99Tc results. By means of the WSC, the 99Tc
      radionuclides ultimately reach the eastern Fram Strait west of Spitsbergen (the
      largest island of the Svalbard archipelago). Results from oceanographic modelling
      and sea ice observations indicate a direct coupling between Kongsfjorden and the
      area west of it. The findings in connection with new radionuclide results
      presented in this paper concur with these assumptions. Furthermore they indicate
      that the inner part of Kongsfjorden is also well linked to the WSC. Surface
      seawater from the central part of the WSC, sampled during a cruise with RV
      Polarstern in the summer of 2000, shows a higher level of 99Tc than those
      measured in Kongsfjorden in spring 2000. However, all levels measured in surface
      water are of the same order of magnitude. Data from sampling of deeper water in
      the WSC area provide information pertaining to the lateral distribution of 99Tc.
      The results, along with additional data from spring 2001, indicate that
      Kongsfjorden is suitable for monitoring the levels of 99Tc arriving in the
      European Arctic and that the sheltered setting of this fjord does not necessarily
      provide protection against pollution from the open sea.

PMID- 12805938
TI  - A process for evaluating adverse environmental impacts by cooling-water system
      entrainment at a California power plant.
AB  - A study to determine the effects of entrainment by the Diablo Canyon Power Plant
      (DCPP) was conducted between 1996 and 1999 as required under Section 316(b) of
      the Clean Water Act. The goal of this study was to present the U.S. Environmental
      Protection Agency (EPA) and Central Coast Regional Water Quality Control Board
      (CCRWQCB) with results that could be used to determine if any adverse
      environmental impacts (AEIs) were caused by the operation of the plant's cooling
      water intake structure (CWIS). To this end we chose, under guidance of the
      CCRWQCB and their entrainment technical working group, a unique approach
      combining three different models for estimating power plant effects: fecundity
      hindcasting (FH), adult equivalent loss (AEL), and the empirical transport model
      (ETM). Comparisons of the results from these three approaches provided us a
      relative measure of confidence in our estimates of effects. A total of 14 target
      larval fish taxa were assessed as part of the DCPP 316(b). Example results are
      presented here for the kelp, gopher, and black-and-yellow (KGB) rockfish complex
      and clinid kelpfish. Estimates of larval entrainment losses for KGB rockfish were
      in close agreement (FH is approximately equals to 550 adult females per year, AEL
      is approximately equals to 1,000 adults [male and female] per year, and ETM =
      larval mortality as high as 5% which could be interpreted as ca. 2,600 1 kg adult
      fish). The similar results from the three models provided confidence in the
      estimated effects for this group. Due to lack of life history information needed
      to parameterize the FH and AEL models, effects on clinid kelpfish could only be
      assessed using the ETM model. Results from this model plus ancillary information
      about local populations of adult kelpfish suggest that the CWIS might be causing
      an AEI in the vicinity of DCPP.

PMID- 12805939
TI  - Comparing Clean Water Act Section 316(b) policy options.
AB  - This paper develops a comparative framework for policy proposals involving fish
      protection and Section 316(b) of the Clean Water Act (CWA). Section 316(b)
      addresses the impingement and entrainment of fish by cooling-water intake
      structures used principally by steam electric power plants. The framework is
      motivated by examining the role of adverse environmental impacts (AEIs) in the
      context of Section 316(b) decision making. AEI is mentioned in Section 316(b),
      but not defined. While various AEI options have been proposed over the years,
      none has been formalized through environmental regulations nor universally
      accepted. Using a multiple values approach from decision analysis, AEIs are
      characterized as measurement criteria for ecological impacts. Criteria for
      evaluating AEI options are identified, including modeling and assessment issues,
      the characterization of ecological value, regulatory implementation, and the
      treatment of uncertainty. Motivated by the difficulties in defining AEI once and
      for all, a framework is introduced to compare options for 316(b) decision making.
      Three simplified policy options are considered, each with a different implicit or
      explicit AEI approach: (1) a technology-driven rule based on a strict reading of
      the 316(b) regulatory text, and for which any impingement and entrainment count
      as AEI, (2) a complementary, open-ended risk-assessment process for estimating
      population effects with AEI characterized on a site-specific basis, and (3) an
      intermediate position based on proxy measures such as specially constructed
      definitions of littoral zone, sensitive habitat, or water body type. The first
      two proposals correspond roughly to responses provided, respectively, by the
      Riverkeeper environmental organization and the Utility Water Act Group to the
      U.S. Environmental Protection Agency (EPA)'s proposed 316(b) new facilities rule
      of August 2000; the third example is a simplified form of the EPA's proposed
      August 2000 new facilities rule itself. The simplified policy positions are
      compared using the three dimensions of the comparative policy framework: (1) the
      role of CWA philosophy or vision, such as the use of technology-forcing rules,
      (2) regulatory policy implementation, and (3) the role for scientific information
      and the knowledge base. Strengths and weaknesses of all three 316(b) policy
      approaches are identified. The U.S. EPA's final new facilities rule of November
      2001 is briefly characterized using the comparative policy framework and used to
      further illustrate the approach.

PMID- 12805940
TI  - Defining "adverse environmental impact" and making paragraph 316(b) decisions: a
      fisheries management approach.
AB  - The electric utility industry has developed an approach for decisionmaking that
      includes a definition of Adverse Environmental Impact (AEI) and an implementation
      process. The definition of AEI is based on lessons from fishery management
      science and analysis of the statutory term "adverse environmental impact" and is
      consistent with current natural resource management policy. The industry has
      proposed a definition focusing on "unacceptable risk to the population"s ability
      to sustain itself, to support reasonably anticipated commercial or recreational
      harvests, or to perform its normal ecological function." This definition focuses
      not on counting individual fish or eggs cropped by the various uses of a water
      body, but on preserving populations of aquatic organisms and their functions in
      the aquatic community. The definition recognizes that assessment of AEI should be
      site-specific and requires both a biological decision and a balancing of diverse
      societal values. The industry believes that the definition of AEI should be
      implemented in a process that will maximize the overall societal benefit of the
      paragraph 316(b) decision by considering the facility"s physical location,
      design, and operation, as well as the local biology. The approach considers
      effects on affected fish and shellfish populations and the benefits of any
      necessary best technology available (BTA) alternatives. This is accomplished
      through consideration of population impacts, which conversely allows
      consideration of the benefits of any necessary BTA modifications. This in turn
      allows selection of BTAs that will protect potentially affected populations in a
      cost-effective manner. The process also employs risk assessment with stakeholder
      participation, in accordance with EPA's Guidelines for Ecological Risk
      Assessment. The information and tools are now available to make informed
      decisions about site-specific impacts that will ensure protection of aquatic
      ecosystems and best serve the public interest.

PMID- 12805941
TI  - Indicators of AEI applied to the Delaware Estuary.
AB  - We evaluated the impacts of entrainment and impingement at the Salem Generating
      Station on fish populations and communities in the Delaware Estuary. In the
      absence of an agreed-upon regulatory definition of "adverse environmental impact"
      (AEI), we developed three independent benchmarks of AEI based on observed or
      predicted changes that could threaten the sustainability of a population or the
      integrity of a community. Our benchmarks of AEI included: (1) disruption of the
      balanced indigenous community of fish in the vicinity of Salem (the "BIC"
      analysis); (2) a continued downward trend in the abundance of one or more
      susceptible fish species (the "Trends" analysis); and (3) occurrence of
      entrainment/impingement mortality sufficient, in combination with fishing
      mortality, to jeopardize the future sustainability of one or more populations
      (the "Stock Jeopardy" analysis). The BIC analysis utilized nearly 30 years of
      species presence/absence data collected in the immediate vicinity of Salem. The
      Trends analysis examined three independent data sets that document trends in the
      abundance of juvenile fish throughout the estuary over the past 20 years. The
      Stock Jeopardy analysis used two different assessment models to quantify
      potential long-term impacts of entrainment and impingement on susceptible fish
      populations. For one of these models, the compensatory capacities of the modeled
      species were quantified through meta-analysis of spawner-recruit data available
      for several hundred fish stocks. All three analyses indicated that the fish
      populations and communities of the Delaware Estuary are healthy and show no
      evidence of an adverse impact due to Salem. Although the specific models and
      analyses used at Salem are not applicable to every facility, we believe that a
      weight of evidence approach that evaluates multiple benchmarks of AEI using both
      retrospective and predictive methods is the best approach for assessing
      entrainment and impingement impacts at existing facilities.

PMID- 12805942
TI  - Adverse environmental impact: a consultant's perspective.
AB  - Environmental consultants are in a unique position to address the practical
      aspects of a working definition of "adverse environmental impact" (AEI) within
      Section 316(b) of the Clean Water Act. In our work with the electric utility
      industry, attorneys, and regulatory agencies, we have encountered numerous and
      sometimes conflicting interpretations as to what constitutes AEI. In our over 30
      years of experience, we have applied most of the approaches suggested for
      addressing this issue, including biostatistical methods, trend analysis, time
      series methods, conditional mortality rate models, stock-recruitment models,
      equivalent adult models, and ecosystem models. In our experience, the paradigm
      most helpful in bringing about agreement among stakeholders is to (1) create a
      model of operating scenarios, (2) use empirical data from on-site studies to
      parameterize the model, (3) convert losses by life stage to equivalent adult
      losses, (4) convert equivalent adult losses to economic value, and (5) compare
      scenarios on an economic basis.

PMID- 12805943
TI  - Using attainment of the designated aquatic life use to determine adverse
      environmental impact.
AB  - Section 316(b) of the Clean Water Act requires that cooling-water intake
      structures (CWIS) use Best Technology Available (BTA) to minimize adverse
      environmental impacts (AEI). The U.S. EPA has not defined AEI, and there is no
      clear consensus regarding its definition. Nonetheless, operational definitions
      are necessary to evaluate design alternatives and to measure the success of
      mitigative measures. Rather than having to develop measures of aquatic health
      that are highly site-specific, controversial, and often unlikely to elicit
      agreement from all sides of the environmental "fence", " it may be more
      productive to use existing ecological assessment tools. Aquatic Life Uses (ALU)
      already provide a regulatory framework to assess the quality (health) of the
      aquatic community in various habitats (e.g., warmwater habitat, exceptional
      warmwater habitat). Attainment of the ALU indicates that further point source
      controls are unnecessary, whereas nonattainment indicates that those pollutants
      or stressors causing the nonattainment must be reduced. A similar approach for
      existing water intakes is recommended. That is, attainment of the designated ALU
      will be taken as an indication that there is no AEI. Although attainment of the
      ALU may not be a foolproof indicator of a lack of AEI, this approach seems more
      reasonable that using scarce monetary resources to fix problems that likely do
      not exist, or having both regulators and the regulated community expend their
      resources debating whether various observed biological responses do or do not
      constitute AEI.

PMID- 12805945
TI  - Sediment remediation for ecosystem in eutrophic lakes.
AB  - The remediation method--namely, a hybrid system combined with DAF and CRM--is
      studied in this paper for the size reduction of aqua-ecological circulation and
      for the elution control in lakes. Results show that two effects on water quality
      purification, the sediment washout effect and the elution control effect, can be
      induced by this system, and the biota inhabiting the lake is therefore shifted
      into an oligotrophic aspect, from blue algae to green algae and/or diatoms.

PMID- 12805946
TI  - The TGF-beta family: signaling pathways, developmental roles, and tumor
      suppressor activities.
AB  - Intercellular communication is a critical process for all multicellular
      organisms, and communication among cells is required for proper embryonic
      development and adult physiology. Members of the Transforming Growth Factor-beta
      (TGF-beta) family of secreted proteins communicate information between cells via
      a complex signaling pathway, and family members are capable of inducing a wide
      range of cellular responses. The purpose of this review is to provide the reader
      with a broad introduction to our current understanding of three aspects of the
      TGF-beta family. These are the molecular mechanisms utilized by TGF-beta
      signaling pathways, the developmental roles played by TGF-beta family members in
      a variety of species, and the growing list of cancers in which various TGF-beta
      signaling pathways display tumor suppressor activity.

PMID- 12805947
TI  - Zooplankton structure and potential food web interactions in the plankton of a
      subtropical chain-of-lakes.
AB  - This study evaluates the taxonomic and size structure of macro-zooplankton and
      its potential role in controlling phytoplankton in the Kissimmee Chain-of-Lakes,
      six shallow interconnected lakes in Florida, U.S. Macro-zooplankton species
      biomass and standard limnological attributes (temperature, pH, total phosphorus
      [TP], chlorophyll a [Chl a], and Secchi transparency) were quantified on a
      bimonthly basis from April 1997 to February 1999. Concentrations of TP ranged
      from below 50 to over 150 microg l(-1). Peak concentrations of particulate P
      coincided with maximal Chl a, and in one instance a high concentration of soluble
      reactive P followed. The cladoceran zooplankton was dominated by small species,
      including Eubosmina tubicen, Ceriodaphnia rigaudi, and Daphnia ambigua. The
      exotic daphnid, D. lumholtzii, periodically was abundant. The copepods were
      strongly dominated by Diaptomus dorsalis, a species previously shown to be highly
      resistant to fish predation. These results, and findings of controlled
      experiments on a nearby lake with a nearly identical zooplankton species
      complement, suggest that fish predation may be a major factor structuring the
      macro-zooplankton assemblage. Zooplankton biomass, on the other hand, may be
      affected by resource availability. There was a significant positive relationship
      between average biomass of macro-zooplankton and the average concentration of TP
      among the six lakes. No such relationship existed between zooplankton biomass and
      Chl a, suggesting that the predominant food web in these systems may be based on
      bacteria-plankton, as has been documented in nearby Lake Okeechobee. All of the
      zooplankton taxa encountered in the Kissimmee Chain-of-Lakes (except Mesocyclops
      edax) are known bacteria grazers in Florida lakes. Phytoplankton biomass,
      measured as Chl a, was strongly associated with TP, both within and across lakes.
      Phytoplankton biomass was not associated with the biomass of zooplankton. These
      results, when considered in the context of nutrient-addition, zooplankton
      exclosure studies on Lake Okeechobee, support the hypothesis that phytoplankton
      biomass in subtropical lakes is regulated by "bottom-up," rather than "top-down"
      forces.

PMID- 12805948
TI  - Cell death and aging--a question of cell type.
AB  - Replicative senescence of human cells in primary culture is a widely accepted
      model for studying the molecular mechanisms of human ageing. The standard model
      used for studying human ageing consists of fibroblasts explanted from the skin
      and grown into in vitro senescence. From this model, we have learned much about
      molecular mechanisms underlying the human ageing process; however, the model
      presents clear limitations. In particular, a long-standing dogma holds that
      replicative senescence involves resistance to apoptosis, a belief that has led to
      considerable confusion concerning the role of apoptosis during human ageing.
      While there are data suggesting that apoptotic cell death plays a key role for
      ageing in vivo and in the pathogenesis of various age-associated diseases, this
      is not reflected in the current literature on in vitro senescence. In this
      article, I summarize key findings concerning the relationship between apoptosis
      and ageing in vivo and also review the literature concerning the role of
      apoptosis during in vitro senescence. Recent experimental findings, summarized in
      this article, suggest that apoptotic cell death (and probably other forms of cell
      death) are important features of the ageing process that can also be
      recapitulated in tissue culture systems to some extent. Another important lesson
      to learn from these studies is that mechanisms of in vitro senescence differ
      considerably between various histotypes.

PMID- 12805950
TI  - Metal concentrations in soil paste extracts as affected by extraction ratio.
AB  - Saturated paste extracts are sometimes used to estimate metal levels in the soil
      solution. To assess the significance of heavy-metal concentrations measured in
      saturation extracts, soil paste extracts were prepared with distilled water in
      amounts ranging from 60-200% of the moisture content at saturation. Trace metals
      behaved as if a small pool consistently was dissolved independent of the
      extraction ratio applied. Metal concentrations in the solution hence were not
      buffered by the solid phase, but the observed behaviour would allow the
      estimation of metal concentrations in the soil solution as a function of moisture
      content. The behaviour of iron and manganese suggested that some microbial
      reduction occurred. The intensity increased with increasing extraction ratio but
      not to the extent of affecting dissolution of trace elements.

PMID- 12805949
TI  - Large-scale mapping and predictive modeling of submerged aquatic vegetation in a
      shallow eutrophic lake.
AB  - A spatially intensive sampling program was developed for mapping the submerged
      aquatic vegetation (SAV) over an area of approximately 20,000 ha in a large,
      shallow lake in Florida, U.S. The sampling program integrates Geographic
      Information System (GIS) technology with traditional field sampling of SAV and
      has the capability of producing robust vegetation maps under a wide range of
      conditions, including high turbidity, variable depth (0 to 2 m), and variable
      sediment types. Based on sampling carried out in August-September 2000, we
      measured 1,050 to 4,300 ha of vascular SAV species and approximately 14,000 ha of
      the macroalga Chara spp. The results were similar to those reported in the early
      1990s, when the last large-scale SAV sampling occurred. Occurrence of Chara was
      strongly associated with peat sediments, and maximal depths of occurrence varied
      between sediment types (mud, sand, rock, and peat). A simple model of Chara
      occurrence, based only on water depth, had an accuracy of 55%. It predicted
      occurrence of Chara over large areas where the plant actually was not found. A
      model based on sediment type and depth had an accuracy of 75% and produced a
      spatial map very similar to that based on observations. While this approach needs
      to be validated with independent data in order to test its general utility, we
      believe it may have application elsewhere. The simple modeling approach could
      serve as a coarse-scale tool for evaluating effects of water level management on
      Chara populations.

PMID- 12805951
TI  - Chromate reduction in Serratia marcescens isolated from tannery effluent and
      potential application for bioremediation of chromate pollution.
AB  - Pollution of aquatic systems by heavy metals has resulted in increasing
      environmental concern because they cannot be biodegraded. One metal that gives
      reason for concern due to its toxicity is chromium. Cr(VI) and Cr(III) are the
      principal forms of chromium found in natural waters. A chromate-resistant strain
      of the bacterium S. marcescens was isolated from tannery effluent. The strain was
      able to reduce Cr(VI) to Cr(III), and about 80% of chromate was removed from the
      medium. The reduction seems to occur on the cell surface. Transmission electron
      microscopic examination of cells revealed that particles were deposited on the
      outside of bacterial cells. A stable biofilm was formed in less than 10 h,
      reaching around 1010 cfu attached per milligram of activated carbon. These
      findings demonstrate that immobilized S. marcescens might be used in industrial
      waste treatment processes.

PMID- 12805952
TI  - Heavy metal concentrations in the spiders Pirata piraticus (Clerck, 1757) and
      Clubiona phragmitis (C.L. Koch, 1843) along the Scheldt Estuary (Belgium).
AB  - Wetland ecosystems may be affected by deposition and accumulation of heavy
      metals. Metal concentrations in the spiders Pirata piraticus and Clubiona
      phragmitis living in marshes along the river Scheldt (Flanders, Belgium) were
      analyzed. The organisms were sampled on seven sites along a gradient from
      freshwater to brackish marshes. Except for lead, P. piraticus contained higher
      metal concentrations than C. phragmitis. This is related to physiological and
      ecological differences between species. No correlation was found between metal
      concentration in the organisms and soil total concentration.

PMID- 12805953
TI  - The tao of hematopoietic stem cells: toward a unified theory of tissue
      regeneration.
AB  - Hematopoietic stem cells (HSCs) are the best studied of the tissue-specific stem
      cells. By definition, HSCs have long been regarded as restricted to formation of
      blood cells of both the lymphoid and myeloid lineages. HSCs residing in the bone
      marrow microenvironment have self-renewal capacity and can repopulate the
      hematopoietic system of irradiated transplant recipients for the lifetime of the
      individual. Therefore, HSCs are extremely important targets for gene therapy
      applications aimed toward the treatment of inherited and acquired blood
      disorders. However, recent studies have suggested that a subpopulation of HSCs
      may have the ability to contribute to diverse cell types such as hepatocytes,
      myocytes, and neuronal cells, especially following induced tissue damage.
      Preclinical amelioration of liver disease and myocardial infarcts by HSC-enriched
      bone marrow cell populations raises the possibility that HSC transplants have the
      potential to provide therapeutic benefit for a wide variety of diseases. These
      surprising findings contradict the dogma that adult stem cells are
      developmentally restricted. Extrapolation of these findings to the clinic will be
      facilitated by prospective identification of the stem cells that possess this
      developmental plasticity. Furthermore, characterization of the signaling pathways
      and molecular determinants regulating the remarkable transdifferentiation
      capacity of these stem cells may provide insight into novel approaches for
      modulating frequency of differentiative potential.

PMID- 12805954
TI  - Ischemia elicits a coordinated expression of pro-survival proteins in mouse
      myocardium.
AB  - Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro
      survival factors occur after myocardial ischemia. To gain an understanding of the
      factors involved with ischemic injury, we examined expression changes in pro
      survival and opposing pro-apoptotic signals at early and chronic periods of
      ischemia using an in vivo murine model. Alterations of pro-survival proteins such
      as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic
      repressor protein (ARC) have not been evaluated in a murine model of cardiac
      ischemia. Early ischemia (1 day) resulted in a 50% reduction in ARC protein
      levels relative to sham-operated left ventricles, without significant changes in
      the expression of xIAP or other pro-survival factors. In contrast, a deficiency
      of xIAP expression was found in cardiac infarcts starting after 1 week,
      concomitant with significant evidence of apoptotic cell death and an up
      regulation of pro-apoptotic signals including Bax, tumor necrosis factor-a, and
      caspase-8 activation. Chronic ischemia (after 2 weeks) was associated with
      elevated levels of other pro-survival factors such as Bcl-xL and the
      phosphorylated form of Akt, as part of the adaptive remodeling of the myocardium.
      Altogether, these findings suggest that strategies to increase IAP expression may
      promote myocyte survival after chronic ischemia.

PMID- 12805956
TI  - Modeling of nitrate leaching during the fall-winter season in artificially
      drained soils.
AB  - The nitrogen processes that occur within the soil play a major role in
      determining the nitrate leaching to shallow groundwater. In this study, the
      transport and fate of nitrate within the soil profile were analyzed by comparing
      field data with the simulation results of a mathematical model. The objective was
      to study the transport and fate of nitrate within the soil profile and nitrate
      leaching to shallow groundwater for the fall-winter season, by applying the
      methodology in Elverdinge experiment, situated in the sandy loam region in
      Belgium, from October 1, 2000 to March 31, 2001. The analysis by comparing field
      data with the simulation results of DRAINMOD-N model is given. The research
      indicated that the DRAINMOD-N model can, after calibration and validation, be
      used as a useful fertilizer management tool in predicting the nitrate transport
      and transformation in the soil profile and the nitrate leaching to shallow
      groundwater and surface waters. The model can also be used as an environmental
      control when the environmental objective has a greater importance than profits in
      the agriculture field.

PMID- 12805957
TI  - Effective monitoring of small river basins.
AB  - As the transport of many pollutants occurs during high floods monitoring programs
      must focus on these intermittent events. In small rivers the pollutants start
      their travel as short pulses often associated with fine particles, but disperse
      on their way downstreams. Therefore the chemical data of a flood event are only
      representative of a small part of the basin adjacent to the monitoring station.
      This is usually not taken into account by evaluating water quality data.

PMID- 12805959
TI  - Ozone risk assessment and mapping in the Alps based on data from passive
      samplers.
AB  - Passive samplers (diffusion tubes with organic reagent, produced by Passam of
      Switzerland) were used in a sampling campaign for the detection of weekly mean
      ozone concentrations in 15 sites over a domain of 80 x 40 km on the southern side
      of the European Alps from May to August 1998. The area is characterized by vast
      natural terrain of complex topography, with conifer and broadleaf forests. It is
      difficult to access and monitor air quality there with continuous analysers. By
      applying geostatistical techniques (ordinary kriging), and correcting the
      interpolated ozone concentrations according to the altitude of each single grid
      cell (2 x 2 km), maps of weekly ozone concentrations were produced. The weekly
      ozone data were used to assess daily and hourly data by means of an iterative
      procedure based on a functional dependence of ozone concentrations both on
      altitude and on the time of day. This allowed the estimation of values with an
      exposure index such as AOT40 (accumulated exposure over the threshold of 40 ppb)
      in all 800 cells of the domain. This also allowed the mapping of risk assessment
      related to the effects of ozone on the regional forest vegetation. Results
      obtained show values that exceed the exposure standards adopted in the Kuopio
      protocol (1996). Excess exposure values also match values calculated over a wider
      territorial domain by using hourly data on ozone concentration derived from
      continuous automatic analysers.

PMID- 12805960
TI  - Genotoxicity and mutagenicity of suspended particulate matter of river water and
      waste water samples.
AB  - Suspended particulate matter of samples of river water and waste water treatment
      plants was tested for genotoxicity and mutagenicity using the standardized umu
      assay and two versions of the Ames microsuspension assay. The study tries to
      determine the entire DNA-damaging potential of the water samples and the
      distribution of DNA-damaging substances among the liquid phase and solid phase.
      Responsiveness and sensitivity of the bioassays are compared.

PMID- 12805961
TI  - Quality control criteria for analysis of organic traces in water.
AB  - The aim of this paper is the discussion of quality control (QC) criteria for
      environmental monitoring of organic contaminants at trace levels in water. In
      addition, QC criteria in the identification and confirmation of target analytes
      have been considered.

PMID- 12805962
TI  - Individual-based modelling: potentials and limitations.
AB  - Individual-based modelling (IBM) is an important option in ecology for the study
      of specific properties of complex ecological interaction networks. The main
      application of this model type is the analysis of population characteristics at
      high resolution. IBM also contributes to the advancement of ecological theory.
      One of the remarkable potentials of the approach is the possibility of studying
      self-organization and emergent properties that arise from individual actions on
      higher integration levels, especially on the population level. This review
      outlines the background and different application fields of individual-based
      models together with a short description of the technical implications of model
      setup. The limitations of this modelling approach result from the technical basis
      of model construction, which can handle a limited number of active entities only.
      Limits in biological knowledge also restrict the application of this model type.
      The paper presents some individual-based models that have been developed for
      different purposes and briefly discusses these models. Concerning the perspective
      of IBM, a coincidence with developments in artificial life research is explained.
      IBM shifts the focus of ecological analysis of dynamic systems from structurally
      fixed settings to the analysis of self-organizing interaction patterns that are
      variable in quantity and quality.

PMID- 12805963
TI  - Field-based supercritical fluid extraction of hydrocarbons at industrially
      contaminated sites.
AB  - Examination of organic pollutants in groundwaters should also consider the source
      of the pollution, which is often a solid matrix such as soil, landfill waste, or
      sediment. This premise should be viewed alongside the growing trend towards field
      based characterisation of contaminated sites for reasons of speed and cost. Field
      based methods for the extraction of organic compounds from solid samples are
      generally cumbersome, time consuming, or inefficient. This paper describes the
      development of a field-based supercritical fluid extraction (SFE) system for the
      recovery of organic contaminants (benzene, toluene, ethylbenzene, and xylene and
      polynuclear aromatic hydrocarbons) from soils. A simple, compact, and robust SFE
      system has been constructed and was found to offer the same extraction efficiency
      as a well-established laboratory SFE system. Extraction optimisation was
      statistically evaluated using a factorial analysis procedure. Under optimised
      conditions, the device yielded recovery efficiencies of >70% with RSD values of
      4% against the standard EPA Soxhlet method, compared with a mean recovery
      efficiency of 48% for a commercially available field-extraction kit. The device
      will next be evaluated with real samples prior to field deployment.

PMID- 12805964
TI  - Antiamoebic chemoprophylaxis using quinfamide in children: a comparative study.
AB  - This study sought to examine whether the administration of quinfamide at 3- or 6
      month intervals diminished the frequency of Entamoeba histolytica cysts in stool
      samples compared to controls. The prospective, longitudinal, randomized, single
      blind study examined children from six primary schools in Celaya and Neutla,
      Guanajuato. Of the 1,524 students in these schools, we selected participants for
      the study as follows: Children were included in the study if their parents agreed
      in writing to the study and if the children demonstrated evidence of E.
      histolytica cysts after a parasitoscopic analysis by concentration (PSC) in three
      samples over consecutive days using Faust"s method. Those included in the study
      received a single 4.3-g/kg dose of quinfamide, and we performed PSC on days 5, 6,
      and 7 following dose administration to examine whether quinfamide had affected
      the presence of the cysts. The study participants who tested negative for cysts
      were divided into three groups: Group 1 had 102 patients who underwent quinfamide
      treatment and three CPS analyses after the 12 months of the study; Group 2 had 98
      subjects who underwent the quinfamide treatment and three CPS analyses at months
      3, 6, 9, and 12 after their entrance into the study; and Group 3 had 102
      patients, who underwent the quinfamide treatment and series of three CPS analyses
      at months 6 and 12 of the study. All participants received the dose of quinfamide
      after providing stool samples and after a clinical gastrointestinal history was
      obtained. Further clinical gastrointestinal data were collected 5 days after the
      quintamide dose was administered. We used EpiInfo 6.0 for statistical analysis,
      calculating c2 and p values for the clinical data and the CPS data after the 12
      months concluded. Of the initial samples of 1,524 subjects, 308 (20.2%) had
      Entamoebic cysts. Of these, six were further eliminated because they did not meet
      the inclusion requirements. At the conclusion of the study, Group 1 presented
      with 37.6% of subjects still testing positive for cysts; of Group 2, 12.5% tested
      positive; and in Group 3, 23.5% of participants tested positive for cysts (chi2 =
      16.8; df = 2; p = 0.0002). For comparisons of groups 1 and 2 and 1 and 3, p <
      0.05; for the comparison of groups 2 and 3, p > 0.05. We conclude that
      antiamoebic chemoprophylaxis can be a choice for control of amoebic infection
      where personal hygiene and food consumption habits are not improving.

PMID- 12805965
TI  - Determination and commitment of mechanosensory hair cells.
AB  - Sound and movement are perceived through the vibration of modified ciliary
      bundles located on the apical surfaces of specialized mechanosensory hair cells.
      These hair cells derive from specific regions of the otocyst that become
      determined to develop initially as sensory epithelia and ultimately as either
      hair cells or supporting cells. The number of hair cells in an individual
      vertebrate is surprisingly small and the ability to replace these cells varies
      among different classes. The molecular and cellular factors that specify hair
      cell identity are not known, but the results of recent experiments have begun to
      identify some of the signaling pathways that play important roles in hair cell
      development. This review will describe recent findings related to the factors
      that influence the final choice of a progenitor cell to develop as a hair cell
      and discuss their implications for the overall development of the auditory and
      vestibular systems.

PMID- 12805966
TI  - Nonylphenol, octyphenol, and bisphenol A in groundwaters as a result of agronomic
      practices.
AB  - Due to increasing concern about the assessment and protection of the quality of
      groundwater as a limited natural resource, an extensive monitoring program has
      been carried out, covering a highly agricultural area of Catalonia where
      different types of crops have been grown during the last 5-10 years. The paper
      reports the analytical protocol used (sampling, filtration, preconcentration, and
      analysis) and the most relevant organic compounds present in groundwaters from
      agricultural areas as well as the concentration levels found.

PMID- 12805967
TI  - The development of a sub-surface monitoring system for organic contamination in
      soils and groundwater.
AB  - A major problem when dealing with environmental contamination is the early
      detection and subsequent surveillance of the contamination. This paper describes
      the potential of sub-surface sensor technology for the early detection of organic
      contaminants in contaminated soils, sediments, and landfill sites. Rugged, low
      power hydrocarbon sensors have been developed, along with a data-logging system,
      for the early detection of phase hydrocarbons in soil. Through laboratory-based
      evaluation, the ability of this system to monitor organic contamination in water
      based systems is being evaluated. When used in conjunction with specific
      immunoassays, this can provide a sensitive and low-cost solution for long-term
      monitoring and analysis, applicable to a wide range of field applications.

PMID- 12805968
TI  - Fate of MTBE and DCPD compounds relative to BTEX in gasoline-contaminated
      aquifers.
AB  - The aim of this communication is to provide preliminary results on MTBE
      monitoring, and at the same time to propose some new tracers of gasoline
      pollution in groundwater. An overview is presented on benzene-toluene
      ethylbenzene-xylene (BTEX), methyl tertiary-butyl ether (MTBE), and
      dicyclopentadienes (DCPD) contents in gasoline formulations. Their specific fate
      in gasoline-contaminated aquifers are consistent with their physical-chemical
      properties.

PMID- 12805969
TI  - Toxicity of single and mixed contaminants in seawater measured with acute
      toxicity bioassays.
AB  - Different types of organic pollutants commonly detected in seawater have been
      evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and
      Selenastrum capricornotum were selected to test toxic effects of individual
      compounds and mixtures of these compounds, obtaining EC50 values in the range of
      0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were
      seen for a clear majority of the cases (>60%). Mixtures containing methyl
      tertiary-butyl ether (MTBE) exhibit accelerated processes that result in a change
      in concentration required to produce a toxic effect; for example, in the case of
      mixtures containing MTBE and Diuron and Dichlofluanid.

PMID- 12805970
TI  - A decontamination process to remove metals and stabilise Montreal sewage sludge.
AB  - The Montreal Urban Community (MUC) treatment plant produces approximately 270
      tons of dry sludge daily (tds/day) during physicochemical wastewater treatment.
      The sludges are burned and contribute to the greenhouse effect by producing
      atmospheric CO2. Moreover, the sludge emanates a nauseating odour during its
      thermal stabilisation and retains unpleasant odours for the part (25%) that is
      dried and granulated. To solve this particular problem, the treatment plant
      authorities are currently evaluating an acidic chemical leaching (sulfuric or
      hydrochloric acid) process at a pH between 2 and 3, using an oxidizing agent such
      as ferric chloride or hydrogen peroxide (METIX-AC technology, patent pending;
      [20]). They could integrate it to a 70 tds/day granulated sludge production
      process. Verification of the application of METIX-AC technology was carried out
      in a pilot plant set up near the sludge production plant of the MUC. The tests
      showed that METIX-AC technology can be advantageously integrated to the process
      used at the MUC. The residual copper (274 +/- 58 mg/kg) and cadmium (5.6 +/- 2.9
      mg/kg) concentrations in the treated sludge meet legislation standards. The
      results have also shown that odours have been significantly eliminated for the
      dewatered, decontaminated, and stabilized biosolids (> 97%) compared to the non
      decontaminated biosolids. A high rate of odour elimination also was obtained for
      the liquid leached biosolids (> 93%), compared to the untreated liquid biosolids.
      The fertilising value (N and P) is well preserved by the METIX-AC process.
      Dissolved organic carbon measurements have showed that little organic matter is
      brought in solution during the treatment. In fact, the average concentration of
      dissolved organic carbon measured in the treated liquid phase is 966 +/- 352
      mg/l, whereas it is 1190 +/- 325 mg/l in untreated sludge. The treated sludge was
      first conditioned with an organic polymer and a coagulant aid. It was
      successfully dewatered with various dehydration equipments (filter press, rotary
      press, centrifuge).

PMID- 12805971
TI  - Environmental radionuclides in surface soils of Vietnam.
AB  - A database on 238U, 232Th, 40K, and 137Cs in surface soils was established to
      provide inputs for the assessment of the collective dose to the population of
      Vietnam and to support soil erosion studies using 137Cs as a tracer. A total of
      292 soil samples was taken from undisturbed sites across the territory and the
      concentrations of radionuclides were determined by gamma spectrometry method. The
      multiple regression of 137Cs inventories against characteristics of sampling
      locations allowed us to establish the distribution of 137Cs deposition density
      and its relationship with latitude and annual rainfall. The 137Cs deposition
      density increases northward and varies from 178 Bq m(-2) to 1,920 Bq m(-2). High
      rainfall areas in the northern and central parts of the country have received
      considerable 137Cs inputs exceeding 600 Bq m-2, which is the maximum value that
      can be expected for Vietnam from the UNSCEAR global pattern. The mean activity
      concentrations of naturally occurring radionuclides 238U, 232Th, and 40K are 45,
      59, and 401 Bq kg(-1), respectively, which entail an average absorbed dose rate
      in air of 62 nGy h(-1), which is about 7% higher than the world average.

PMID- 12805972
TI  - Express detection of pentachlorophenol as dioxins precursor in natural water.
AB  - A rapid detection method for the pesticide pentachlorophenol (PCP)--polarization
      fluoroimmunoassay (PFIA)--in the dynamic range of 10-9,000 ppb was developed. PCP
      may form polychlorinated dibenzo-p-dioxins, making environmental monitoring of
      this compound an issue of great importance. In order to optimize the PFIA
      procedure, a number of fluorescein-labeled PCP derivatives and similar compounds
      (tracers) were synthesized, and the influence of their structure on PFIA
      characteristics was studied. Also, two antisera were tested in developing PFIA
      for PCP. The developed method is highly specific for PCP and can be used for its
      determination in water samples at a level down to 10 ppb. Total time of the assay
      for 10 samples is about 7 min. The assay provides a useful and a highly practical
      screening tool for the processing of large numbers of samples and for the
      preliminary estimation of potential dioxins contamination in water resources.

PMID- 12805973
TI  - Ionic surface active compounds in atmospheric aerosols.
AB  - Surfactants in the atmosphere have several potential roles in atmospheric
      chemistry. They can form films on aqueous surfaces, which lowers the surface
      tension and possibly delays water evaporation and gaseous transportation across
      the aqueous interface. They can also increase the solubility of organic compounds
      in the aqueous phase. Recently, the decrease of surface tension in cloud growing
      droplets has been suggested as relevant to increases in the number of droplets of
      smaller size, potentially enhancing cloud albedo. Natural surfactants in the lung
      aid gas transfer and influence the dissolution rate of aerosol particles, so
      surfactants in atmospheric aerosols, once inhaled, may interact with pulmonary
      surfactants. Ambient aerosols were collected from the edge of Norwich, a small
      city in a largely agricultural region of England, and analysed for surfactants.
      Methylene blue, a conventional dye for detecting anionic surfactants, has been
      used as a colorimetric agent. The concentration of surfactants expressed as
      methylene blue active substances (MBAS) is in the range of 6-170 pmol m(-3)(air).
      A negative correlation with chloride aerosol indicates that these surfactants are
      probably not the well-known surfactants derived from marine spray. A more
      positive correlation with aerosol nitrate and gaseous NOx supports an association
      with more polluted inland air masses. The surfactants found in aerosols seem to
      be relatively strong acids, compared with weaker acids such as the long-chain
      carboxylic acids previously proposed as atmospheric surfactants. Surfactants from
      the oxidation of organic materials (perhaps vegetation- or soil-derived) seem a
      likely source of these substances in the atmosphere.

PMID- 12805974
TI  - Neural induction, neural fate stabilization, and neural stem cells.
AB  - The promise of stem cell therapy is expected to greatly benefit the treatment of
      neurodegenerative diseases. An underlying biological reason for the progressive
      functional losses associated with these diseases is the extremely low natural
      rate of self-repair in the nervous system. Although the mature CNS harbors a
      limited number of self-renewing stem cells, these make a significant contribution
      to only a few areas of brain. Therefore, it is particularly important to
      understand how to manipulate embryonic stem cells and adult neural stem cells so
      their descendants can repopulate and functionally repair damaged brain regions. A
      large knowledge base has been gathered about the normal processes of neural
      development. The time has come for this information to be applied to the problems
      of obtaining sufficient, neurally committed stem cells for clinical use. In this
      article we review the process of neural induction, by which the embryonic
      ectodermal cells are directed to form the neural plate, and the process of neural
      fate stabilization, by which neural plate cells expand in number and consolidate
      their neural fate. We will present the current knowledge of the transcription
      factors and signaling molecules that are known to be involved in these processes.
      We will discuss how these factors may be relevant to manipulating embryonic stem
      cells to express a neural fate and to produce large numbers of neurally
      committed, yet undifferentiated, stem cells for transplantation therapies.

PMID- 12805975
TI  - Analysis of Australian legislation dealing with contaminated land.
AB  - An analysis of past and present Australian legislation for managing and
      regulating contaminated sites confirms that such legislation must deal with a
      number of specific matters. Australian legislation is effective in some of these
      areas but poor in relation to others. The analysis will assist other countries
      and jurisdictions to create effective legislation more speedily by avoiding
      identified problems.

PMID- 12805976
TI  - Effects of Eucalyptus plantations on detritus, decomposers, and detritivores in
      streams.
AB  - Vast areas of the Iberian Peninsula are covered by monocultures of the exotic
      tree Eucalyptus globulus. Given that (1) leaf litter produced in the riparian
      areas is the main energy source for small streams, and (2) trees differ in their
      nutrient content, chemical defenses, and physical attributes, eucalypt
      plantations have the potential to affect the biology of streams. Research teams
      from the University of Coimbra and the University of the Basque Country have been
      addressing the potential effects of eucalypt plantations at several levels of
      study. Here we review the main conclusions of these investigations. Eucalypt
      plantations produced less litter than some deciduous forests. However, there were
      marked differences in timing of litterfall: litter production peaked during
      autumn in deciduous forests, whereas in the eucalypt forests it tended to peak in
      summer and to be more evenly distributed throughout the year. Despite these
      differences, the average standing stock of organic matter was higher in the
      eucalypt than in the deciduous forest. This may be attributed to (1) the
      occurrence of spates or heavy rain in autumn, the period of maximum litter fall
      in deciduous forests, and (2) bark accumulation in eucalypt forests. Because of
      differences in leaf composition, the nutrient input in eucalypt forests seems to
      be lower than in deciduous forests. The rate of decomposition of eucalypt leaves
      was strongly dependent on nutrients in the water: in nutrient-poor waters it was
      slower than that of most other leaf species, whereas in nutrient-rich waters it
      can be as fast as alder--a fast-decaying species. The biomass and cumulative
      diversity of aquatic hyphomycetes colonizing leaves did not differ between
      eucalypt and other native leaf species, but fungal sporulation generally peaked 2
      weeks later on eucalypt leaves. This lag disappeared when lipids (but not
      polyphenolics) were chemically removed from eucalypt leaves. Similarly, addition
      of eucalypt oils to culture media retarded or suppressed fungal growth. Streams
      bordered by Eucalyptus had lower diversity of fungal spores (but similar spore
      densities) in Portugal; less consistent patterns were found in similar
      experiments in Spain. Eucalyptus leaves proved to be poor food for shredders.
      Under laboratory conditions leaves of Eucalyptus ranked low in food selection
      experiments using native shredders. The same shredders failed to grow and died
      when fed exclusively eucalypt leaves. The removal of oils from eucalypt leaves
      resulted in increased feeding rates, whereas the transfer of oils to alder leaves
      resulted in decreased feeding rates. The effect of eucalypt plantations on stream
      invertebrate communities is not very consistent. In nutrient-poor waters, fewer
      invertebrates colonized eucalypt than alder leaves, but this effect was mitigated
      after a microbial conditioning period in nutrient-rich waters. Portuguese streams
      bordered by Eucalyptus had lower numbers of invertebrates than streams surrounded
      by deciduous forests. In Spanish streams differences were less marked and
      nonexistent when looking at the composition of the communities, which change more
      from year to year than from site to site. Most of the eucalypt streams studied in
      Portugal and Spain dried up in summer, a fact that might reflect an increase in
      soil hydrophobity produced by Eucalyptus plantations. The very short planting-to
      harvest period of eucalypt plantations results in additional impacts, such as
      soil loss, siltation of streams, or reduced amounts of woody debris in stream
      channels, which affects their capacity to retain leaf-litter, as well as the
      availability of habitat for invertebrates and fish. The studies by the Portuguese
      and Spanish research teams confirm the importance of maintaining riparian buffer
      strips to reduce human impact on streams and rivers.

PMID- 12805977
TI  - Uncertainty and conservatism in assessing environmental impact under paragraph
      316(b): lessons from the Hudson River case.
AB  - Initially, regulation of cooling water intakes under paragraph 316(b) was
      extremely conservative due to the rapid increase predicted for generating
      capacity, and to the uncertainty associated with our knowledge of the effects of
      entrainment and impingement. The uncertainty arose from four main sources:
      estimation of direct plant effects; understanding of population regulatory
      processes; measurement of population parameters; and predictability of future
      conditions. Over the last quarter-century, the uncertainty from the first three
      sources has been substantially reduced, and analytical techniques exist to deal
      with the fourth. In addition, the dire predictions initially made for some water
      bodies have not been realized, demonstrating that populations can successfully
      withstand power plant impacts. This reduced uncertainty has resulted in less
      conservative regulation in some, but not all venues. New York appears to be
      taking a more conservative approach to cooling water intakes. The conservative
      approach is not based on regulations, but in a philosophy that power plant
      mortality is an illegitimate use of the aquatic resources. This philosophy may
      simplify permitting decisions, but it does not further the development of a
      science-based definition of adverse environmental impact.

PMID- 12805978
TI  - A holistic look at minimizing adverse environmental impact under Section 316(b)
      of the Clean Water Act.
AB  - Section 316(b) of the Clean Water Act (CWA) requires that "the location, design,
      construction, and capacity of cooling water intake structures reflect the best
      technology available for minimizing adverse environmental impact." As the U.S.
      Environmental Protection Agency (EPA) develops new regulations to implement
      Section 316(b), much of the debate has centered on adverse impingement and
      entrainment impacts of cooling-water intake structures. Depending on the specific
      location and intake layout, once-through cooling systems withdrawing many
      millions of gallons of water per day can, to a varying degree, harm fish and
      other aquatic organisms in the water bodies from which the cooling water is
      withdrawn. Therefore, opponents of once-through cooling systems have encouraged
      the EPA to require wet or dry cooling tower systems as the best technology
      available (BTA), without considering site-specific conditions. However, within
      the context of the broader scope of the CWA mandate, this focus seems too narrow.
      Therefore, this article examines the phrase "minimizing adverse environmental
      impact" in a holistic light. Emphasis is placed on the analysis of the terms
      "environmental" and "minimizing." Congress chose "environmental" in lieu of other
      more narrowly focused terms like "impingement and entrainment," "water quality,"
      or "aquatic life." In this light, BTA for cooling-water intake structures must
      minimize the entire suite of environmental impacts, as opposed to just those
      associated with impingement and entrainment. Wet and dry cooling tower systems
      work well to minimize entrainment and impingement, but they introduce other
      equally important impacts because they impose an energy penalty on the power
      output of the generating unit. The energy penalty results from a reduction in
      plant operating efficiency and an increase in internal power consumption. As a
      consequence of the energy penalty, power companies must generate additional
      electricity to achieve the same net output. This added production leads to
      additional environmental impacts associated with extraction and processing of the
      fuel, air emissions from burning the fuel, and additional evaporation of
      freshwater supplies during the cooling process. Wet towers also require the use
      of toxic biocides that are subsequently discharged or disposed. The other term
      under consideration, "minimizing," does not equal "eliminating." Technologies may
      be available to minimize but not totally eliminate adverse environmental impacts.

PMID- 12805979
TI  - Modeling possible cooling-water intake system impacts on Ohio River fish
      populations.
AB  - To assess the possible impacts caused by cooling-water intake system entrainment
      and impingement losses, populations of six target fish species near power plants
      on the Ohio River were modeled. A Leslie matrix model was constructed to allow an
      evaluation of bluegill, freshwater drum, emerald shiner, gizzard shad, sauger,
      and white bass populations within five river pools. Site-specific information on
      fish abundance and length-frequency distribution was obtained from long-term Ohio
      River Ecological Research Program and Ohio River Sanitation Commission (ORSANCO)
      electrofishing monitoring programs. Entrainment and impingement data were
      obtained from 316(b) demonstrations previously completed at eight Ohio River
      power plants. The model was first run under a scenario representative of current
      conditions, which included fish losses due to entrainment and impingement. The
      model was then rerun with these losses added back into the populations,
      representative of what would happen if all entrainment and impingement losses
      were eliminated. The model was run to represent a 50-year time period, which is a
      typical life span for an Ohio River coal-fired power plant. Percent changes
      between populations modeled with and without entrainment and impingement losses
      in each pool were compared to the mean interannual coefficient of variation (CV),
      a measure of normal fish population variability. In 6 of the 22 scenarios of fish
      species and river pools that were evaluated (6 species x 5 river pools, minus 8
      species/river pool combinations that could not be evaluated due to insufficient
      fish data), the projected fish population change was greater than the expected
      variability of the existing fish population, indicating a possible adverse
      environmental impact. Given the number of other variables affecting fish
      populations and the conservative modeling approach, which assumed 100% mortality
      for all entrained fish and eggs, it was concluded that the likelihood of impact
      was by no means assured, even in these six cases. It was concluded that in most
      cases, current entrainment and impingement losses at six Ohio River power plants
      have little or no effect at the population level.

PMID- 12805980
TI  - Japanese application of bioassays for environmental management.
AB  - The increasing number of existing and new chemicals demands ecotoxicological data
      as well as toxicological data for pre- and postmarketing risk assessments.
      Although human health has been the major concern in Japanese environmental
      management, ecosystem health is becoming the big issue as the need for preserving
      the diversity of ecosystems has been recognized. This recognition is changing the
      regulatory framework in Japan, resulting in new actions toward establishment of
      water-quality standards for aquatic organisms and ecotoxicological assessment of
      existing chemicals. At the same time, the need to assess complex liquids that
      contain several kinds of chemicals is increasing. The ecotoxicological study of
      Japanese effluents shows that the present chemical-specific standards are not
      enough to protect aquatic ecosystems. These two factors encourage the application
      of ecotoxicological tests as well as the toxicological data.

PMID- 12805981
TI  - Latent fingerprint detection with SYPRO Rose Plus Protein Blot Stain.
AB  - Lanthanide complexes are employed in photoluminescence detection of fingerprints
      because their long luminescence lifetimes allow use of time-resolved imaging
      techniques to suppress problematic background fluorescence. To date, however,
      these complexes have been unsuccessful when used in developing old fingerprints
      on porous substrates. SYPRO Rose Plus Protein Blot Stain remedies this
      shortcoming; it lends itself to smooth surfaces as well, thus having potential as
      a universal fingerprint reagent.

PMID- 12805982
TI  - Assessment of land-use impact on macroinvertebrate communities in the Zwalm River
      basin (Flanders, Belgium) using multivariate analysis and geographic information
      systems.
AB  - Relationships between land-use and river water quality assessed by means of
      biological and physical-chemical variables and habitat characteristics were
      analysed for the Zwalm River basin in Flanders (Belgium). The research focussed
      on three zones within this river basin, each characterized by different land
      uses, and consequently, different types of pollution, mainly of diffuse origin.
      Environmental data have been integrated within a Geographic Information System.
      Possible relationships between aquatic ecosystem and land-use variables were
      searched for by means of multivariate analysis.

PMID- 12805983
TI  - The bacterial microflora of fish.
AB  - The results of numerous studies indicate that fish possess bacterial populations
      on or in their skin, gills, digestive tract, and light-emitting organs. In
      addition, the internal organs (kidney, liver, and spleen) of healthy fish may
      contain bacteria, but there is debate on whether or not muscle is actually
      sterile. The numbers and taxonomic composition of the bacterial populations often
      reflect those of the surrounding water. The role of the bacteria includes the
      ability to degrade complex molecules (therefore exercising a potential benefit in
      nutrition), to produce vitamins and polymers, and to be responsible for the
      emission of light by the light-emitting organs of deep-sea fish. Taxa, including
      Pseudomonas, may contribute to spoilage by the production of histamines in fish
      tissue.

PMID- 12805984
TI  - Desorption techniques for determination of metals mobility in soils.
AB  - Three leaching techniques for assessment of fixed and mobile metal or
      radionuclides in soils are demonstrated on radiocaesium speciation. A new
      leaching technique based on the variation of the leaching solution volume to
      solid phase amount is proposed. It enables parallel treatment of large numbers of
      samples and, therefore, is suitable for a routine analysis of contaminant
      mobility in soils. As a leaching solution, 1 M ammonium acetate is proposed for
      caesium, but any other desorption solution harmonised with existing speciation
      schemes can be used.

PMID- 12805985
TI  - Recent developments in the methods of estimating shooting distance.
AB  - A review of developments during the past 10 years in the methods of estimating
      shooting distance is provided. This review discusses the examination of clothing
      targets, cadavers, and exhibits that cannot be processed in the laboratory. The
      methods include visual/microscopic examinations, color tests, and instrumental
      analysis of the gunshot residue deposits around the bullet entrance holes. The
      review does not cover shooting distance estimation from shotguns that fired
      pellet loads.

PMID- 12805986
TI  - Effects of climate warming, North Atlantic Oscillation, and El Nino-Southern
      Oscillation on thermal conditions and plankton dynamics in northern hemispheric
      lakes.
AB  - Impacts of climate warming on freshwater ecosystems have been documented recently
      for a variety of sites around the globe. Here we provide a review of studies that
      report long-term (multidecadal) effects of warming trends on thermal properties
      and plankton dynamics in northern hemispheric lakes. We show that higher lake
      temperatures, shorter periods with ice cover, and shorter stagnation periods were
      common trends for lakes across the hemisphere in response to the warmer
      conditions. Only for shallow dimictic lakes was it observed that deep-water
      temperatures decreased. Moreover, it became evident that phytoplankton dynamics
      and primary productivity altered in conjunction with changes in lake physics.
      Algal spring blooms developed early and were more pronounced in several European
      lakes after mild winters with short ice cover periods, and primary productivity
      increased in North American lakes. Effects of elevated temperatures on
      zooplankton communities were seen in an early development of various species and
      groups, as is documented for cladocerans, copepods, and rotifers in European
      lakes. Furthermore, thermophile species reached higher abundance in warmer years.
      Obviously, the nature of responses is species specific, and depends on the
      detailed seasonal patterning of warming. Complex responses such as effects
      propagating across trophic levels are likely, indicating that observed climate
      ecosystem relationships are not generally applicable. Nonetheless, the picture
      emerges that climate-driven changes in freshwater ecosystems may be synchronised
      to a certain extent among lakes even over great distances if climatic influences
      are not masked by anthropogenic impacts or differences in lake morphology. Macro
      scale climatic fluctuations--such as the North Atlantic Oscillation or the El
      Nino-Southern Oscillation--were identified as the most important candidates
      responsible for such coherence, with the former predominating in Europe and the
      latter in North America. We emphasise, however, that the driving mechanisms and
      the future behaviour of these oscillations are rather uncertain, which
      complicates extrapolation of observed effects into the future. Thus, it is
      necessary to quantify the most important climate-ecosystem relationships in
      models of appropriate complexity. Such models will help elucidate the multiple
      pathways climate affects freshwater ecosystems, and will indicate possible
      adverse effects of a warmer future climate.

PMID- 12805987
TI  - Optimisation of the monitoring strategy of macroinvertebrate communities in the
      river Dender, in relation to the EU Water Framework Directive.
AB  - The Dender basin in Flanders (Belgium) was used as a case study to implement the
      European Union (EU) Water Framework Directive. During the last 5 years, ample
      research on pollution loads and ecological water quality has been done on the
      Dender River. In addition to biological sampling of macroinvertebrates and fish,
      automated measurement stations were also used to investigate the spatial-temporal
      variability of the physical-chemical water quality. This research revealed that
      the pollution of the Dender River is highly variable. The high nutrient loads
      result in severe algae blooms during summer, leading to very complex diurnal
      processes. In this paper, the monitoring strategy for the assessment of the
      biological water quality in the Dender basin has been reviewed in relation to the
      EU Water Framework Directive. For this, seasonal macroinvertebrate data were
      collected and assessed. General trends and hidden structures in these data were
      analysed by means of classification trees, using different inputs (seasons, river
      types, and subbasins). Validation of the results was obtained by applying
      statistical methods. Analysis about the presence and abundance of the
      macroinvertebrates revealed that there is a distinct difference between the
      biological water quality in the Dender stem river and its tributaries. There are
      also seasonal differences between the macroinvertebrate communities when the
      Dender and its tributaries are examined separately. An optimised monitoring
      strategy is proposed based on these results and the EU Water Framework Directive.
      This includes two monitoring campaigns in summer and winter every 3 years.
      Furthermore, a cyclic monitoring scheme was developed to minimise sampling
      efforts.

PMID- 12805988
TI  - Differential gene expression and aging.
AB  - It has been established that an intricate program of gene expression controls
      progression through the different stages in development. The equally complex
      biological phenomenon known as aging is genetically determined and
      environmentally modulated. This review focuses on the genetic component of aging,
      with a special emphasis on differential gene expression. At least two genetic
      pathways regulating organism longevity act by modifying gene expression. Many
      genes are also subjected to age-dependent transcriptional regulation. Some age
      related gene expression changes are prevented by caloric restriction, the most
      robust intervention that slows down the aging process. Manipulating the
      expression of some age-regulated genes can extend an organism's life span.
      Remarkably, the activity of many transcription regulatory elements is linked to
      physiological age as opposed to chronological age, indicating that orderly and
      tightly controlled regulatory pathways are active during aging.

PMID- 12805989
TI  - Cannabinoids on the brain.
AB  - Cannabis has a long history of consumption both for recreational and medicinal
      uses. Recently there have been significant advances in our understanding of how
      cannabis and related compounds (cannabinoids) affect the brain and this review
      addresses the current state of knowledge of these effects. Cannabinoids act
      primarily via two types of receptor, CB1 and CB2, with CB1 receptors mediating
      most of the central actions of cannabinoids. The presence of a new type of brain
      cannabinoid receptor is also indicated. Important advances have been made in our
      understanding of cannabinoid receptor signaling pathways, their modulation of
      synaptic transmission and plasticity, the cellular targets of cannabinoids in
      different central nervous system (CNS) regions and, in particular, the role of
      the endogenous brain cannabinoid (endocannabinoid) system. Cannabinoids have
      widespread actions in the brain: in the hippocampus they influence learning and
      memory; in the basal ganglia they modulate locomotor activity and reward
      pathways; in the hypothalamus they have a role in the control of appetite.
      Cannabinoids may also be protective against neurodegeneration and brain damage
      and exhibit anticonvulsant activity. Some of the analgesic effects of
      cannabinoids also appear to involve sites within the brain. These advances in our
      understanding of the actions of cannabinoids and the brain endocannabinoid system
      have led to important new insights into neuronal function which are likely to
      result in the development of new therapeutic strategies for the treatment of a
      number of key CNS disorders.

PMID- 12805990
TI  - Did the CP audits promote the enterprises' CP? A case study in Beijing.
AB  - Seven enterprises that have had recent Cleaner Production (CP) audits in Beijing
      were interviewed to identify whether these enterprises implemented the audit
      recommendations. If enterprises did implement the recommendations, their reasons
      and the results were analyzed. Finally, some suggestions on how to promote
      enterprise-wide CP were given.

PMID- 12805992
TI  - Functional evaluations in the monitoring of the river ecosystem processes: the
      Adige River as a case stu.
AB  - A model of analysis and environmental evaluation was applied to 11 stretches of
      the Adige River, where an innovative procedure was carried out to interpret
      ecological results. Within each stretch, the most suitable methods were used to
      assess the quality and processes of flood plains, banks, water column, bed, and
      interstitial environment. Indices were applied to evaluate the wild state and
      ecological quality of the banks (wild state index, buffer strip index) and the
      landscape quality of wide areas of the fluvial corridor (environmental landscape
      index). The biotic components (i.e., macrozoobenthos, phytoplankton and
      zooplankton, interstitial hyporheic fauna, vegetation in the riparian areas) were
      analysed by both quantitative and functional methods (as productivity, litter-
      processing and colonisation). The results achieved were then translated into five
      classes of functional evaluation. These qualitative assessments have thus
      preserved a high level of precision and sensitivity in quantifying both the
      quality of the environmental conditions and the integrity of the ecosystem
      processes. Read together with urban planning data, they indicate what actions are
      needed to restore and rehabilitate the Adige River corridor.

PMID- 12805991
TI  - Organotin pollution in China.
AB  - A preliminary investigation of the occurrence of butyltin compounds was made in
      various environmental samples including water, sediment, sea products, and other
      commodities from China. Detection was carried out by the method of hydrogenation
      coupled with SPME or Grignard derivatization, followed by GC-FPD analysis. The
      results showed the universal existence of butyltin compounds in a wide range of
      tested samples, which was a potential danger for human health. Urgent control or
      management of organotin compounds is necessary to prevent the underlying hazard
      caused by this kind of pollutant.

PMID- 12805993
TI  - Hypothesis: Ran GTPase-based potential therapeutic interventions against lethal
      microbial infections.
AB  - Host innate immune response represents a vital immediate defense against
      infections by a diverse group of microorganisms that include bacteria, viruses,
      and fungi. Many types of cell surface receptors in mammalian cells specifically
      recognize particular groups of microorganisms and transmit response signals to
      the nuclei via multiple signal transduction pathways. These signaling pathways
      must merge at some point and are likely to be redundant, as the host innate
      immune response to many microorganisms is remarkably similar; it is characterized
      by the production of proinflammatory cytokines such as TNFalpha, IL-1, and IL-6
      by the principal cell types--macrophages and dendritic cells. Since these
      cytokines influence greatly the magnitude of the cascade of inflammatory events,
      the proportion and the actual amount of each among the cytokine group may be a
      characteristic of each type of infections. Immune modulation by systematically up
      regulate or down-modulate these cytokines would conceivably have major
      therapeutic potential. We have recently shown that two alleles of Ran cDNAs-
      RanT/n and RanC/d--may possess these characteristics. Thus the application of Ran
      to the treatment of septic shock, lethal anthrax shock, or adenovirus-induced
      toxicities may open up many interesting possibilities in the future.

PMID- 12805994
TI  - Formation of neural precursor cell populations by differentiation of embryonic
      stem cells in vitro.
AB  - Recent interest in the generation of neural lineages by differentiation of
      embryonic stem cells arises from the opportunities represented by a
      developmentally normal, unlimited source of material that can be manipulated
      genetically with precision. Several experimental approaches, which differ
      conceptually, in the route of differentiation and the characteristics of the
      resulting cell population have been reported. In this review we undertake a
      comparative analysis of these approaches and their suitability for experimental
      investigation or implantation.

PMID- 12805995
TI  - An interactive database of cocaine-responsive gene expression.
AB  - The postgenomic era of large-scale gene expression studies is inundating drug
      abuse researchers and many other scientists with findings related to gene
      expression. This information is distributed across many different journals, and
      requires laborious literature searches. Here, we present an interactive database
      that combines existing information related to cocaine-mediated changes in gene
      expression in an easy-to-use format. The database is limited to statistically
      significant changes in mRNA or protein expression after cocaine administration.
      The Flash-based program is integrated into a Web page, and organizes changes in
      gene expression based on neuroanatomical region, general function, and gene name.
      Accompanying each gene is a description of the gene, links to the original
      publications, and a link to the appropriate OMIM (Online Mendelian Inheritance in
      Man) entry. The nature of this review allows for timely modifications and rapid
      inclusion of new publications, and should help researchers build second
      generation hypotheses on the role of gene expression changes in the physiology
      and behavior of cocaine abuse. Furthermore, this method of organizing large
      volumes of scientific information can easily be adapted to assist researchers in
      fields outside of drug abuse.

PMID- 12805996
TI  - Uranium speciation and bioavailability in aquatic systems: an overview.
AB  - The speciation of uranium (U) in relation to its bioavailability is reviewed for
      surface waters (fresh- and seawater) and their sediments. A summary of available
      analytical and modeling techniques for determining U speciation is also
      presented. U(VI) is the major form of U in oxic surface waters, while U(IV) is
      the major form in anoxic waters. The bioavailability of U (i.e., its ability to
      bind to or traverse the cell surface of an organism) is dependent on its
      speciation, or physicochemical form. U occurs in surface waters in a variety of
      physicochemical forms, including the free metal ion (U4+ or UO2(2+)) and
      complexes with inorganic ligands (e.g., uranyl carbonate or uranyl phosphate),
      and humic substances (HS) (e.g., uranyl fulvate) in dissolved, colloidal, and/or
      particulate forms. Although the relationship between U speciation and
      bioavailability is complex, there is reasonable evidence to indicate that UO2(2+)
      and UO2OH+ are the major forms of U(VI) available to organisms, rather than U in
      strong complexes (e.g., uranyl fulvate) or adsorbed to colloidal and/or
      particulate matter. U(VI) complexes with inorganic ligands (e.g., carbonate or
      phosphate) and HS apparently reduce the bioavailability of U by reducing the
      activity of UO2(2+) and UO2OH+. The majority of studies have used the results
      from thermodynamic speciation modeling to support these conclusions. Time
      resolved laser-induced fluorescence spectroscopy is the only analytical technique
      able to directly determine specific U species, but is limited in use to
      freshwaters of low pH and ionic strength. Nearly all of the available information
      relating the speciation of U to its bioavailability has been derived using
      simple, chemically defined experimental freshwaters, rather than natural waters.
      No data are available for estuarine or seawater. Furthermore, there are no
      available data on the relationship between U speciation and bioavailability in
      sediments. An understanding of this relationship has been hindered due to the
      lack of direct quantitative U speciation techniques for particulate phases. More
      robust analytical techniques for determining the speciation of U in natural
      surface waters are needed before the relationship between U speciation and
      bioavailability can be clarified.

PMID- 12805997
TI  - Altered short-term synaptic plasticity in mice lacking the metabotropic glutamate
      receptor mGlu7.
AB  - Eight subtypes of metabotropic glutamate (mGlu) receptors have been identified of
      which two, mGlu5 and mGlu7, are highly expressed at synapses made between CA3 and
      CA1 pyramidal neurons in the hippocampus. This input, the Schaffer collateral
      commissural pathway, displays robust long-term potentiation (LTP), a process
      believed to utilise molecular mechanisms that are key processes involved in the
      synaptic basis of learning and memory. To investigate the possible function in
      LTP of mGlu7 receptors, a subtype for which no specific antagonists exist, we
      generated a mouse lacking this receptor, by homologous recombination. We found
      that LTP could be induced in mGlu7-/- mice and that once the potentiation had
      reached a stable level there was no difference in the magnitude of LTP between
      mGlu7-/- mice and their littermate controls. However, the initial decremental
      phase of LTP, known as short-term potentiation (STP), was greatly attenuated in
      the mGlu7-/- mouse. In addition, there was less frequency facilitation during,
      and less post-tetanic potentiation following, a high frequency train in the mGlu7
      /- mouse. These results show that the absence of mGlu7 receptors results in
      alterations in short-term synaptic plasticity in the hippocampus.

PMID- 12806000
TI  - Downstream effects of a hydroelectric reservoir on aquatic plant assemblages.
AB  - Macrophytes were studied downstream of the Rophemel hydroelectric dam on the
      River Rance (Cotes d'Armor Department, western France) to assess the effects of
      hydroelectric functioning on river macrophyte communities. We studied ten
      representative sections of the hydro-peaking channel on five occasions in 1995
      and 1996, on a 15-km stretch of river. Floristic surveys were carried out on
      sections 50 m in length, and genera of macroalgae, species of bryophyta,
      hydrophytes, and emergent rhizophytes were identified. For the aquatic bryophytes
      and spermatophytes section of our study, we compared our results with 19th
      century floristic surveys, before the dam was built. During the vegetative growth
      period, the hydro-peaking frequency was low. The plant richness was highest near
      the dam. The macrophyte communities were highly modified according to the
      distance to the dam. The frequency and magnitude of hydro-peaking was related to
      the aquatic macrophyte richness in an Intermediate Disturbance Hypothesis
      position. However, the results of the eco-historical comparison with 19th century
      floristic surveys point to the original nature of the flora found at the site.
      Some floral patterns, seen during both periods and at an interval of 133 years,
      were indicative of the ubiquity of the aquatic flora and of the plants"
      adaptability. This demonstrates the importance of taking river basin history into
      account in such biological surveys.

PMID- 12806001
TI  - Can drug-drug interactions be predicted from in vitro studies?
AB  - Potential drug-drug interactions as well as drug-xenobiotic interactions are a
      major source of clinical problems, sometimes with dramatic consequences.
      Investigation of drug-drug interactions during drug development is a major
      concern for the drug companies while developing new drugs. Our knowledge of the
      drug-metabolising enzymes, their mechanism of action, and their regulation has
      made considerable progress during the last decades. Various efficient in vitro
      approaches have been developed during recent years and powerful computer-based
      data handling is becoming widely available. All these tools allow us to initiate,
      early in the development of new chemical entities, large-scale studies on the
      interactions of drugs with selective cytochrome P-450 (CYP) isozymes, drug
      receptors, and other cellular entities. Standardisation and validation of these
      methodological approaches significantly improve the quality of the data generated
      and the reliability of their interpretation. The simplicity and the low costs
      associated with the use of in vitro techniques have made them a method of choice
      to investigate drug-drug interactions. Promising successes have been achieved in
      the extrapolation of in vitro data to the in vivo situation and in the prediction
      of drug-drug interaction. Nevertheless, linking in vitro and in vivo studies
      still remains fraught with difficulties and should be made with great caution.

PMID- 12806002
TI  - Potential trace metal-organic complexation in the atmosphere.
AB  - It is possible that metal-organic complexation enhances the uptake of gaseous
      organic compounds and the solubility of metals in aerosols and atmospheric water.
      We investigated potential atmospheric organic ligands and the enhanced uptake of
      hydroxy-, oxo-, and dicarboxylic acids as well as dicarbonyls into atmospheric
      aqueous aerosol. We examined complexation with transition metals (iron,
      manganese, nickel, copper, zinc) and lead on the basis of available references
      and our experimental data. Humic-like substances are most likely ligands in the
      atmosphere, although this is a poorly characterized material. A number of
      polycarboxylic acids and hydroxy forms (e.g., citric and tartronic acids)
      effectively complex metals such as copper in atmospheric aerosols. The simple
      equilibrium model calculations show that the effect of the complexation on the
      gas-aqueous phase partition of gaseous atmospheric ligands is quite small for the
      ligands with the high physical Henry's law constants, e.g., dicarboxylic acids
      represented by oxalic acid, even if they have high affinity with metal ions. The
      lower Henry's law constants of the alpha-dicarbonyls, such as glyoxal and
      methylglyoxal, mean that the complexation could lead to profound increases in
      their partition into the aqueous phase. Despite quantum mechanical arguments for
      copper-glyoxal complexes, experiments showed no evidence of complexation between
      either hydrated or unhydrated alpha-dicarbonyls and the cupric ion. By contrast
      the beta-dicarbonyl, malondialdehyde, has properties that would allow it to
      partition into atmospheric water via the complexation with metal ions under some
      conditions.

PMID- 12806003
TI  - Founding editorial--bone biology.
AB  - The skeleton is a complicated vertebrate structure, comprised of bone cells that
      form, modulate, and resorb the extracellular structure of bone. It is the
      extracellular structure, made up of the bone mineral (largely calcium phosphate)
      and the bone matrix, which constitutes the visible skeleton and the mechanical
      support for the vertebrate body. The matrix is the protein structure on which the
      bone mineral is laid down, many components of which have been identified in
      recent years.

PMID- 12806004
TI  - Pharmacogenetics of antiplatelet drugs.
AB  - Pharmacogenetics refers to the genetic factors that influence the response to a
      drug, often involving genetic variations in drug metabolizing enzymes. The
      pharmacogenetics of antiplatelet agents is in its infancy and largely reflects
      variations in drug targets or related genes. One particular gene variant, the
      PlA2 polymorphism of the glycoprotein (GP) IIb/IIIa receptor, is now emerging as
      a probable determinant of the response to antiplatelet agents including
      GPIIb/IIIa antagonists. This variant may in part explain the heterogeneity in the
      response to GPIIb/IIIa antagonists. The PlA2 genotype appears to be associated
      with an adverse outcome in patients treated with an oral GPIIb/IIIa antagonist
      and may be a factor in the observed failure of these agents in unselected
      populations. However, there are preliminary indications that other antiplatelet
      agents may have an enhanced effect in PlA2 subjects. Further clinical trials in
      particular are required to definitively characterize the pharmacogenetic effect
      of PlA2. Other polymorphisms are also likely to contribute to the
      pharmacogenetics of antiplatelet agents, but these await investigation.

PMID- 12806005
TI  - Induction of primordial germ cells from pluripotent epiblast.
AB  - The formation of germ cells during embryogenesis bears the ultimate importance
      for the continuation of every species. It becomes evident that mechanisms
      governing germ cell fate specification are not well conserved across the animal
      kingdom. In most of the invertebrate and nonmammalian vertebrate species, certain
      maternally derived factors are key to the establishment of germ cell lineage. In
      contrast, mouse primordial germ cells (PGCs) are induced from the pluripotent
      epiblast cells before and during gastrulation by the extraembryonic cell-derived
      signals. The molecular identity for some of these signals has recently been
      revealed by genetic and epiblast culture experiments. Both bone morphogenetic
      proteins 4 (Bmp4) and 8b (Bmp8b) are expressed in the extraembryonic ectoderm and
      are required for PGC formation. Furthermore, BMP4 or BMP8B alone are unable to
      induce PGCs from cultured epiblasts, while they can in combination, indicating
      they signal through separate receptor complexes. In addition, Bmp4 homozygous
      embryos cannot be induced to form PGCs by the synergistic action of BMP4 and
      BMP8B, suggesting that BMP4 proteins produced by pregastrula embryos are required
      for epiblast cells to maintain pluripotency. Moreover, Bmp2, a close relative of
      Bmp4, is expressed in visceral endoderm at the time of PGC specification, and
      inactivation of Bmp2 results in a reduction in PGC number, revealing a novel
      function of visceral endoderm in PGC generation in the mouse.

PMID- 12806006
TI  - Artichoke cultivars (var. "Blanca de Tudela") under elevated ozone
      concentrations.
AB  - Ozone concentrations rise to phytotoxic levels from spring to autumn at western
      Mediterranean basin coastal sites, where artichoke is one of the most important
      crops. Simultaneously, from year to year and especially since the early 1980s,
      resprouting of the stumps has been decreasing in Valencian Community artichoke
      plantations. To see if ozone might be playing a role in this decrease, a number
      of plants were exposed to different levels of ozone. Results of the ozone
      treatments showed reduced biomass in the offshoots of plants exposed to the
      highest ozone treatment. The exposure to ambient ozone during the stump
      establishment period, when compared to filtered-air conditions, resulted in a
      reduction in yield when plants were transplanted in the field under ambient ozone
      concentrations. And when plants were exposed to acute short picks, typical ozone
      visual injury appeared in the older leaves.

PMID- 12806007
TI  - Screening and selection of hypoallergenic buckwheat species.
AB  - Both common buckwheat (Fagopyrum esculentum) flour and meal cause an allergy in
      sensitive patients, and if unnoticed, it can be fatal. It has become a potential
      occupational hazard for some mill workers. The development of hypoallergenic
      buckwheat would be more efficient if natural mutants for allergenic protein are
      detected. A screening and selection method was developed using SDS-PAGE coupled
      with PCR techniques. SDS-PAGE analysis of 14 different species of buckwheat
      revealed that F. lineare and F. urophyllum lack the 22-kDa major allergenic
      protein. PCR-based screening with specific primers for sequences encoding the
      allergenic protein was also effective in distinguishing the allergen-deficient
      species.

PMID- 12806008
TI  - Anthropogenic effects on forest ecosystems at various spatio-temporal scales.
AB  - The focus in this review of long-term effects on forest ecosystems is on human
      impact. As a classification of this differentiated and complex matter, three
      domains of long-term effects with different scales in space and time are
      distinguished: Exploitation and conversion history of forests in areas of
      extended human settlement, Long-range air pollution and acid deposition in
      industrialized regions, Current global loss of forests and soil degradation.
      There is an evident link between the first and the third point in the list.
      Cultivation of primary forestland--with its tremendous effects on land cover-
      took place in Europe many centuries ago and continued for centuries.
      Deforestation today is a phenomenon predominantly observed in the developing
      countries, yet it threatens biotic and soil resources on a global scale.
      Acidification of forest soils caused by long-range air pollution from
      anthropogenic emission sources is a regional to continental problem in
      industrialized parts of the world. As a result of emission reduction legislation,
      atmospheric acid deposition is currently on the retreat in the richer
      industrialized regions (e.g., Europe, U.S., Japan); however, because many other
      regions of the world are at present rapidly developing their polluting industries
      (e.g., China and India), "acid rain" will most probably remain a serious
      ecological problem on regional scales. It is believed to have caused considerable
      destabilization of forest ecosystems, adding to the strong structural and
      biogeochemical impacts resulting from exploitation history. Deforestation and
      soil degradation cause the most pressing ecological problems for the time being,
      at least on the global scale. In many of those regions where loss of forests and
      soils is now high, it may be extremely difficult or impossible to restore forest
      ecosystems and soil productivity. Moreover, the driving forces, which are
      predominantly of a demographic and socioeconomic nature, do not yet seem to be
      lessening in strength. It can only be hoped that a wise policy of international
      cooperation and shared aims can cope with this problem in the future.

PMID- 12806010
TI  - Receptor model source apportionment of nonmethane hydrocarbons in Mexico City.
AB  - With the purpose of estimating the source contributions of nonmethane
      hydrocarbons (NMHC) to the atmosphere at three different sites in the Mexico City
      Metropolitan Area, 92 ambient air samples were measured from February 23 to March
      22 of 1997. Light- and heavy-duty vehicular profiles were determined to
      differentiate the NMHC contribution of diesel and gasoline to the atmosphere.
      Food cooking source profiles were also determined for chemical mass balance
      receptor model application. Initial source contribution estimates were carried
      out to determine the adequate combination of source profiles and fitting species.
      Ambient samples of NMHC were apportioned to motor vehicle exhaust, gasoline
      vapor, handling and distribution of liquefied petroleum gas (LP gas), asphalt
      operations, painting operations, landfills, and food cooking. Both gasoline and
      diesel motor vehicle exhaust were the major NMHC contributors for all sites and
      times, with a percentage of up to 75%. The average motor vehicle exhaust
      contributions increased during the day. In contrast, LP gas contribution was
      higher during the morning than in the afternoon. Apportionment for the most
      abundant individual NMHC showed that the vehicular source is the major
      contributor to acetylene, ethylene, pentanes, n-hexane, toluene, and xylenes,
      while handling and distribution of LP gas was the major source contributor to
      propane and butanes. Comparison between CMB estimates of NMHC and the emission
      inventory showed a good agreement for vehicles, handling and distribution of LP
      gas, and painting operations; nevertheless, emissions from diesel exhaust and
      asphalt operations showed differences, and the results suggest that these
      emissions could be underestimated.

PMID- 12806011
TI  - Community structure of terrestrial invertebrates inhabiting a tidal marsh islet
      in the Mediterranean Sea (Gulf of Gabes, Tunisia).
AB  - The composition of the terrestrial arthropod community of a tidal marsh islet in
      the Gulf of Gabes (Tunisia) was studied during two seasons (spring, autumn). The
      study was conducted on a small islet located in an area where the highest tidal
      excursions of the Mediterranean occur. Standard trapping methods (pitfall traps,
      mobile cages) were used to evaluate specie richness and abundance in different
      areas of the islet. Diversity indices were calculated for coleopterans and
      isopods alone. The structure of the arthropod community varied a great deal from
      one season to the other and differences were found when seaward areas were
      compared with landward ones. El Bessila presented a particularly rich beetle
      community whereas only few isopod species occurred. The moderately high diversity
      levels found for the beetle indicate the influence of the high tidal excursions
      in modelling the structure of the community.

PMID- 12806012
TI  - Maryland power plant cooling-water intake regulations and their application in
      evaluation of adverse environmental impact.
AB  - Maryland's cooling-water intake and discharge regulations, the Code of Maryland
      Regulations (COMAR) 26.08.03, stem from Sections 316(a) and (b) of the Clean
      Water Act (CWA). COMAR 26.08.03.05 and litigative and administrative rulings
      stipulate that the location, design, construction, and capability of cooling
      water intake structures must reflect the best technology available (BTA) for
      minimizing adverse environmental impacts (AEIs), providing that the costs of
      implementing the BTA are not wholly disproportionate to the expected
      environmental benefits. Maryland law exempts facilities that withdraw less than
      10 million gallons/day (MGD) and less than 20% of stream or net flow by the
      intake. If not exempt, BTA must be installed if the cost of doing so is less than
      five times the value of fish impinged annually. Through site-specific studies and
      the use of a Spawning and Nursery Area of Consequence (SNAC) model applied to
      Representative Important Species, several power plants were evaluated to
      determine if they have had an adverse effect on spawning and nursery areas of
      consequence. Examples of application of the Maryland law to a number of power
      plants in the state are presented, together with the outcome of their evaluation.

PMID- 12806013
TI  - Scientific and societal considerations in selecting assessment endpoints for
      environmental decision making.
AB  - It is sometimes argued that, from an ecological point of view, population-,
      community-, and ecosystem-level endpoints are more relevant than individual-level
      endpoints for assessing the risks posed by human activities to the sustainability
      of natural resources. Yet society values amenities provided by natural resources
      that are not necessarily evaluated or protected by assessment tools that focus on
      higher levels of biological organization. For example, human-caused stressors can
      adversely affect recreational opportunities that are valued by society even in
      the absence of detectable population-level reductions in biota. If protective
      measures are not initiated until effects at higher levels of biological
      organization are apparent, natural resources that are ecologically important or
      highly valued by the public may not be adequately protected. Thus, environmental
      decision makers should consider both scientific and societal factors in selecting
      endpoints for ecological risk assessments. At the same time, it is important to
      clearly distinguish the role of scientists, which is to evaluate ecological
      effects, from the role of policy makers, which is to determine how to address the
      uncertainty in scientific assessment in making environmental decisions and to
      judge what effects are adverse based on societal values and policy goals.

PMID- 12806014
TI  - Adverse environmental impact: 30-year search for a definition.
AB  - Since passage of the Clean Water Act in 1972, there has been a long, unresolved
      struggle to define a key phrase in Section 316(b) of the act: "adverse
      environmental impact" (AEI). Section 316(b) requires that the best technology
      available be used in cooling-water intake structures to minimize AEI due to
      entrainment and impingement of aquatic organisms. Various attempts were made to
      evaluate and define AEI, including focused national conferences on impact
      assessment. Unresolved arguments regarding AEI were reinvigorated following the
      1995 Consent Decree requiring EPA to propose new rules to implement Section
      316(b). This article reviews and compares eight proposed definitions of AEI. Six
      of the definitions define AEI as impact expressed at the population or higher
      level of biological organization. The two remaining definitions are unrelated to
      populations: a 1% cropping of the near-field organisms and "one fish equals AEI".
      The latter definition is based on the desire of some stakeholders to define AEI
      as the loss of any public trust resources. Equating loss of public trust
      resources with AEI hampers consensus on a definition because a societal-based
      policy concept (public trust resources) is commingled with science-based
      definitions based on population effects. We recommend that a population-based
      definition of AEI be incorporated into Section 316(b) guidance and observe that
      this will not preclude a state from exercising its law and policy to protect
      public trust resources.

PMID- 12806015
TI  - The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and
      increases its accuracy.
AB  - Proofreading function by the 3'-->5' exonuclease of DNA polymerase delta (pol
      delta) is consistent with the observation that delta efficiency of the associated
      exonuclease can lead to a strong mutation phenotype, high error rates during DNA
      replication, and ultimately cancer. We have isolated pol delta from isotonic (pol
      delta(i)) and detergent (pol delta(d)) calf thymus extracts. Pol delta had a 20
      fold higher ratio of exonuclease to DNA polymerase than pol deltai. This was due
      to the physical association of the TREX2 3'-->5' exonuclease to pol delta(d),
      which was missing from pol delta(i). Pol delta(d) was fivefold more accurate than
      pol i under error-prone conditions (1 mM dGTP and 20 dATP, dCTP, and dTTP) in a
      M13mp2 DNA forward mutation assay, and fourfold more accurate than pol delta(i)
      under error-prone conditions (1 mM dGTP and 20 microM dATP, dCTP, and dTTP) in a
      M13mp2 DNA forward mutation assay, and fourfold more accurate in an M13mp2T90
      reversion assay. Under error-free conditions (20 microM each of the four dNTPs),
      however, both polymerases showed equal fidelity. Our data suggested that
      autonomous 3' --> 5' exonucleases, such as TREX2, through its association with
      pol delta can guarantee high fidelity under difficult conditions in the cell
      (e.g., imbalance of dNTPs) and can add to the accuracy of the DNA replication
      machinery, thus preventing mutagenesis.

PMID- 12806016
TI  - Ozone and plants: need for a biologically based air quality standard.
AB  - For the past 10 years, I have spent parts of late July and early August in
      central Europe, assessing ozone injury symptom expression on native plants in
      upland meadows and along forest edges. Much of this work has been done with local
      colleagues in and near the Tatra Mountains in southern Poland and eastern
      Slovakia and in the Carpathian Mountains in western Ukraine. Active and passive
      ozone air monitors and samplers were also used at most of the study sites.

PMID- 12806017
TI  - Piscivores, trophic cascades, and lake management.
AB  - The concept of cascading trophic interactions predicts that an increase in
      piscivore biomass in lakes will result in decreased planktivorous fish biomass,
      increased herbivorous zooplankton biomass, and decreased phytoplankton biomass.
      Though often accepted as a paradigm in the ecological literature and adopted by
      lake managers as a basis for lake management strategies, the trophic cascading
      interactions hypothesis has not received the unequivocal support (in the form of
      rigorous experimental testing) that might be expected of a paradigm. Here we
      review field experiments and surveys, testing the hypothesis that effects of
      increasing piscivore biomass will cascade down through the food web yielding a
      decline in phytoplankton biomass. We found 39 studies in the scientific
      literature examining piscivore effects on phytoplankton biomass. Of the studies,
      22 were confounded by supplemental manipulations (e.g., simultaneous reduction of
      nutrients or removal of planktivores) and could not be used to assess piscivore
      effects. Of the 17 nonconfounded studies, most did not find piscivore effects on
      phytoplankton biomass and therefore did not support the trophic cascading
      interactions hypothesis. However, the trophic cascading interactions hypothesis
      also predicts that lake systems containing piscivores will have lower
      phytoplankton biomass for any given phosphorus concentration. Based on regression
      analyses of chlorophyll-total phosphorus relationships in the 17 nonconfounded
      piscivore studies, this aspect of the trophic cascading interactions hypothesis
      was supported. The slope of the chlorophyll vs. total phosphorus regression was
      lower in lakes with planktivores and piscivores compared with lakes containing
      only planktivores but no piscivores. We hypothesize that this slope can be used
      as an indicator of "functional piscivory" and that communities with extremes of
      functional piscivory (zero and very high) represent classical 3- and 4-trophic
      level food webs.

PMID- 12806018
TI  - Mobilisation and bioavailability of arsenic around mesothermal gold deposits in a
      semiarid environment, Otago, New Zealand.
AB  - Arsenopyrite (FeAsS) is the principal arsenic (As) mineral in mineralised
      mesothermal veins (typically 5,000 mg/kg As) in southeastern New Zealand.
      Groundwater in contact with arsenopyrite-bearing rocks has elevated As
      concentrations (up to 0.1 mg/l). The arsenopyrite decomposes slowly on oxidation
      in soils and historic mine workings in a cool semiarid climate. Dissolved As is
      predominantly As(III) in association with arsenopyrite, but this is rapidly
      oxidised over days to weeks to As(V) in the vadose zone. Oxidation is facilitated
      by particulate Fe and/or Mn oxyhydroxides, and by bacteria in surface waters.
      Evaporative concentration of dissolved As(V) in the vadose zone causes
      precipitation of scorodite (Fe(III)As(V)O4*2H2O). Adsorption of As(V) to Fe
      oxyhydroxides in soils and groundwater pathways lowers dissolved As
      concentrations. Soils over mineralised veins typically have <200 mg/kg As, as
      most As is removed in solution on geological time scales. Most plants on the
      mineralised rocks and soils do not take up As, although some inedible species can
      fix up to 18 mg/kg As. Hence, bioavailability of As(V) is low in this
      environment, despite the substantial As flux. Similar As mobility is seen in an
      active gold mine processing plant and tailings. Arsenopyrite dissolves more
      rapidly on agitation, and mine waters can have dissolved As >200 mg/l,
      predominantly as As(V). This dissolved As decreases in tailings waters to near 2
      mg/l, mainly as As(III) when in contact with arsenopyrite. Weak oxidation of
      evaporatively dried tailings causes cementation with scorodite and iron
      oxyhydroxides, and scorodite precipitation exerts some control on dissolved As(V)
      concentrations. High dissolved As in mine waters is lowered by adsorption to iron
      oxyhydroxides, and waters discharged from the mine site have negligible dissolved
      As.

PMID- 12806019
TI  - An update on blood pressure short-term variability.
AB  - This article summarizes current achievements of computer-based methodologies in
      identifying the constituting components of short-term blood pressure variability
      and the underlying regulatory mechanisms. It emphasizes the contribution of
      spectral methodologies in early diagnosis of blood pressure deregulations.
      Moreover, the effects of antihypertensive drugs, as well as of new, nonpeptide
      vasopressin antagonists on short-term blood pressure variability, are briefly
      described.

PMID- 12806020
TI  - Lysophospholipid growth factors and their G protein-coupled receptors in
      immunity, coronary artery disease, and cancer.
AB  - The physiological lysophospholipids (LPLs), exemplified by lysophosphatidic acid
      (LPA) and sphingosine 1-phosphate (S1P), are omnific mediators of normal cellular
      proliferation, survival, and functions. Although both LPA and S1P attain
      micromolar concentrations in many biological fluids, numerous aspects of their
      biosynthesis, transport, and metabolic degradation are unknown. Eight members of
      a new subfamily of G protein-coupled LPA/S1P receptors, originally termed Edg Rs,
      bind either LPA or S1P with high affinity and transduce a series of growth
      related and/or cytoskeleton-based functional responses. The most critical areas
      of LPL biology and pathobiology are neural development and neurodegeneration,
      immunity, atherosclerosis and myocardial injury, and cancer. Data from analyses
      of T cells established two basic points: (1) the plasticity and adaptability of
      expression of LPA/S1P Rs by some cells as a function of activation, and (2) the
      role of opposing signals from two different receptors for the same ligand as a
      mechanism for fine control of effects of LPLs. In the heart, LPLs may promote
      coronary atherosclerosis, but are effectively cytoprotective for hypoxic cardiac
      myocytes and those exposed to oxygen free radicals. The findings of production of
      LPA by some types of tumor cells, overexpression of selected sets of LPA
      receptors by the same tumor cells, and augmentation of the effects of protein
      growth factors by LPA have suggested pathogenetic roles for the LPLs in cancer.
      The breadth of physiologic and pathologic activities of LPLs emphasizes the
      importance of developing bioavailable nonlipid agonists and antagonists of the
      LPA/S1P receptors for diverse therapeutic applications.

PMID- 12806021
TI  - Evolutionary theories of aging and longevity.
AB  - The purpose of this article is to provide students and researchers entering the
      field of aging studies with an introduction to the evolutionary theories of
      aging, as well as to orient them in the abundant modern scientific literature on
      evolutionary gerontology. The following three major evolutionary theories of
      aging are discussed: 1) the theory of programmed death suggested by August
      Weismann, 2) the mutation accumulation theory of aging suggested by Peter
      Medawar, and 3) the antagonistic pleiotropy theory of aging suggested by George
      Williams. We also discuss a special case of the antagonistic pleiotropy theory,
      the disposable soma theory developed by Tom Kirkwood and Robin Holliday. The
      theories are compared with each other as well as with recent experimental
      findings. At present the most viable evolutionary theories are the mutation
      accumulation theory and the antagonistic pleiotropy theory; these theories are
      not mutually exclusive, and they both may become a part of a future unifying
      theory of aging. Evolutionary theories of aging are useful because they open new
      opportunities for further research by suggesting testable predictions, but they
      have also been harmful in the past when they were used to impose limitations on
      aging studies. At this time, the evolutionary theories of aging are not ultimate
      completed theories, but rather a set of ideas that themselves require further
      elaboration and validation. This theoretical review article is written for a wide
      readership.

PMID- 12806022
TI  - Chiral pesticides in soil and water and exchange with the atmosphere.
AB  - The enantiomers of chiral pesticides are often metabolised at different rates in
      soil and water, leading to nonracemic residues. This paper reviews
      enantioselective metabolism of organochlorine pesticides (OCPs) in soil and
      water, and the use of enantiomers to follow transport and fate processes.
      Residues of chiral OCPs and their metabolites are frequently nonracemic in soil,
      although exceptions occur in which the OCPs are racemic. In soils where
      enantioselective degradation and/or metabolite formation has taken place, some
      OCPs usually show the same degradation preference--e.g., depletion of (+)trans
      chlordane (TC) and (-)cis-chlordane (CC), and enrichment of the metabolite
      (+)heptachlor exo-epoxide (HEPX). The selectivity is ambivalent for other
      chemicals; preferential loss of either (+) or (-)o,p-DDT and enrichment of either
      (+) or (-)oxychlordane (OXY) occurs in different soils. Nonracemic OCPs are found
      in air samples collected above soil which contains nonracemic residues. The
      enantiomer profiles of chlordanes in ambient air suggests that most chlordane in
      northern Alabama air comes from racemic sources (e.g., termiticide emissions),
      whereas a mixture of racemic and nonracemic (volatilisation from soil) sources
      supplies chlordane to air in the Great Lakes region. Chlordanes and HEPX are also
      nonracemic in arctic air, probably the result of soil emissions from lower
      latitudes. The (+) enantiomer of alpha-hexachlorocyclohexane (alpha-HCH) is
      preferentially metabolised in the Arctic Ocean, arctic lakes and watersheds, the
      North American Great Lakes, and the Baltic Sea. In some marine regions (the
      Bering and Chukchi Seas, parts of the North Sea) the preference is reversed and (
      )alpha-HCH is depleted. Volatilisation from seas and large lakes can be traced by
      the appearance of nonracemic alpha-HCH in the air boundary layer above the water.
      Estimates of microbial degradation rates for alpha-HCH in the eastern Arctic
      Ocean and an arctic lake have been made from the enantiomer fractions (EFs) and
      mass balance in the water column. Apparent pseudo first-order rate constants in
      the eastern Arctic Ocean are 0.12 year(-1) for (+)alpha-HCH, 0.030 year(-1) for (
      )alpha-HCH, and 0.037 year(-1) for achiral gamma-HCH. These rate constants are 3
      10 times greater than those for basic hydrolysis in seawater. Microbial breakdown
      may compete with advective outflow for long-term removal of HCHs from the Arctic
      Ocean. Rate constants estimated for the arctic lake are about 3-8 times greater
      than those in the ocean.

PMID- 12806023
TI  - Megacities and the environment.
AB  - The world's 25 largest cities comprise only 4% of the global population, but they
      have substantial impacts on the environment at multiple scales. Here we review
      what is known of the biogeochemistry of these megacities. Climatic, demographic,
      and economic data show no patterns across cities, save that wealthier cities have
      lower growth rates. The flows of water, fuels, construction materials, and food
      are examined where data are available. Water, which by mass dwarfs the other
      inputs, is not retained in urban systems, whereas construction materials and food
      predominate in the urban infrastructure and the waste stream. Fuels are
      transformed into chemical wastes that have the most far-reaching and global
      impacts. The effects of megacity resource consumption on geologic, hydrologic,
      atmospheric, and ecological processes are explored at local, regional, and global
      scales. We put forth the concepts of urban metabolism and urban succession as
      organizing concepts for data collection, analysis, and synthesis on urban
      systems. We conclude that megacities are not the final stage of urban evolution;
      rather, the climax of urban development will occur at a global scale when human
      society is at steady state with resource supply rates.

PMID- 12806024
TI  - Recent trends in the development of ecological models applied on aquatic
      ecosystems.
AB  - This paper presents an overview of the application of models on aquatic
      ecosystems. More than 17% of the models published in the focal journal in the
      field, Ecological Modelling, are aquatic ecosystem models. An increasing number
      of papers are dealing with the theoretical aspects of modeling--new modeling
      approaches and techniques, how models can be used to reveal ecosystem properties,
      and how models can better reflect the properties of ecosystems. This development
      implies that today we have more types of models. The characteristics, the
      advantages, and the disadvantages of these model types are presented briefly. The
      selection criteria for the presented model types are discussed, and the
      application of these types to models for aquatic ecosystems is reviewed. A recent
      improvement in model calibration of particular interest for aquatic ecosystems is
      presented, and the perspectives resulting from this new calibration procedure and
      from possible hybrids of the presented model types are discussed.

PMID- 12806025
TI  - Bioremediation of heavy metals and organic toxicants by composting.
AB  - Hazardous organic and metallic residues or by-products can enter into plants,
      soils, and sediments from processes associated with domestic, municipal,
      agricultural, industrial, and military activities. Handling, ingestion,
      application to land or other distributions of the contaminated materials into the
      environment might render harm to humans, livestock, wildlife, crops, or native
      plants. Considerable remediation of the hazardous wastes or contaminated plants,
      soils, and sediments can be accomplished by composting. High microbial diversity
      and activity during composting, due to the abundance of substrates in feedstocks,
      promotes degradation of xenobiotic organic compounds, such as pesticides,
      polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs).
      For composting of contaminated soils, noncontaminated organic matter should be
      cocomposted with the soils. Metallic pollutants are not degraded during
      composting but may be converted into organic combinations that have less
      bioavailability than mineral combinations of the metals. Degradation of organic
      contaminants in soils is facilitated by addition of composted or raw organic
      matter, thereby increasing the substrate levels for cometabolism of the
      contaminants. Similar to the composting of soils in vessels or piles, the on-site
      addition of organic matter to soils (sheet composting) accelerates degradation of
      organic pollutants and binds metallic pollutants. Recalcitrant materials, such as
      organochlorines, may not undergo degradation in composts or in soils, and the
      effects of forming organic complexes with metallic pollutants may be nonpermanent
      or short lived. The general conclusion is, however, that composting degrades or
      binds pollutants to innocuous levels or into innocuous compounds in the finished
      product.

PMID- 12806026
TI  - Soluble HLA class I molecules/CD8 ligation trigger apoptosis of CD8+ cells by
      Fas/Fas-ligand interaction.
AB  - The human major histocompatibility complex (HLA) encodes two sets of HLA class I
      molecules, which have been termed class Ia (or classical) and class Ib (or
      nonclassical) molecules. The class Ia molecules include the gene products of HLA
      A, HLA-B, and HLA-C loci and are characterized by broad tissue expression and by
      a high degree of polymorphism. The class Ib molecules include the gene products
      of HLA-E, HLA-F, and HLA-G loci and are characterized by a restricted tissue
      distribution and by limited polymorphism. Besides being expressed on nucleated
      cells, classical and nonclassical HLA class I molecules are present in serum in
      soluble form (sHLA-I). The serum level of sHLA-I molecules is significantly
      increased in a variety of physiological and pathological conditions such as
      pregnancy, acute rejection episodes following organ allografts, acute graft
      versus-host-disease (GVHD) following bone marrow transplantation, autoimmune
      diseases, viral infections, and malignant melanoma. Because of the statistically
      significant association with clinical parameters, the level of sHLA-I antigens
      has been suggested to represent a useful marker to predict the evolution of viral
      infections and to monitor the clinical course of allografts. Moreover, elevated
      levels of functional sHLA-I and soluble Fas-ligand molecules have been detected
      by our group in blood components and might play a role in the immunomodulatory
      effect of autologous and allogeneic transfusions. Several lines of evidence
      suggest that sHLA-I molecules are immunologically functional and may play an
      immunoregulatory role. In fact, they have been shown to elicit antibodies in both
      allogeneic and xenogeneic combinations, to inhibit the activity of alloreactive
      cytotoxic T lymphocytes (CTL), and to induce apoptosis in alloreactive and virus
      specific CTL, in activated autologous and allogeneic CD8+ T cells, and in CD8+ NK
      cells. There is general agreement about the mechanism underlying the inhibition
      of CTL activity by sHLA antigens. This inhibition appears to be mediated by
      interactions of sHLA-I antigens a1 and a2 domains with T cell receptor (TCR). By
      contrast, there is conflicting information about the mechanism underlying
      induction of apoptosis of activated T cells by sHLA-I antigens. Several authors
      reported that sHLA-I molecules induced apoptosis of alloreactive CD8+ cytotoxic T
      lymphocytes through interaction with their TCR. However, our own data and those
      other groups indicate that classical and nonclassical sHLA-I molecules trigger
      Fas/Fas-ligand mediated apoptosis of phytohemoagglutinin (PHA)-activated and
      virus-specific CD8+ T lymphocytes as well as of CD8+ NK cells by interacting with
      CD8 coreceptor. Recently, we performed a series of experiments in our laboratory
      to clarify the intracellular mechanism(s) leading to Fas-ligand upregulation and
      secretion. These unpublished data indicate that sHLA-I/CD8 ligation elicits the
      phosphorylation of p56lck protein thyrosin kinase (PTK) associated with CD8
      cytoplasmic domain in the absence of any other TCR-derived signal, the activation
      of syk-like ZAP-70 PTK and protein kinase C, and extracellular calcium influx.
      Then, activation and nuclear translocation of NF-kB and NF-AT occurs, leading to
      Fas-ligand mRNA transcription and soluble Fas-ligand secretion, which delivers
      the death signal. Interestingly, soluble Fas-ligand secretion and CD8+ cell
      apoptosis, but not CD8+ cell cytolitic activity, are completely inhibited by
      Cyclosporin A, which specifically blocks the activation of the
      calcineurin/calmodulin pathway. Taken together, these data suggest that sHLA-I
      molecules are involved in a signal-transduction pathway leading to Fas-ligand
      expression, soluble Fas-ligand secretion, and CD8+ cells apoptosis.

PMID- 12806027
TI  - P2 receptors and platelet activation.
AB  - Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by
      activating platelets. In platelets, the classical P2T receptor is now resolved
      into three P2 receptor subtypes: the P2Y1, the P2Y12, and the P2X1 receptors.
      Both pharmacological and molecular biological approaches have confirmed the role
      of the P2Y1 and P2Y12 receptors in the ADP-induced platelet fibrinogen receptor
      activation. The P2Y1 and the P2X1 receptors independently contribute to platelet
      shape change. Whereas the P2Y12 receptor mediates the potentiation of dense
      granule release reaction, both the P2Y1 and P2Y12 receptors play an important
      role in the ADP-induced phospholipase A2 activation. The signaling events
      downstream of these receptors leading to the physiological effects remain
      elusive, and they are yet to be delineated.

PMID- 12806029
TI  - Experimental and theoretical study of the enthalpy of formation of 3,6-diphenyl
      1,2,4,5-tetroxane molecule.
AB  - We report the results obtained for the experimental determination and the
      theoretical calculation of the enthalpy of formation of 3,6-diphenyl-1,2,4,5
      tetroxane molecule. The experimental work was performed using a macrocalorimeter
      to measure the combustion heat, and the sublimation enthalpy was determined via
      the measurement of the vapor pressure at equilibrium with the vapor phase at
      different temperatures resorting to the Clapeyron-Claussius equation. Theoretical
      calculations were performed using semiempirical AM1 and PM3 methods as well as ab
      initio techniques at the 3-21, 6-31G(d,p), and 6-311G(d,p) basis set levels.

PMID- 12806028
TI  - Coupling planar cell polarity signaling to morphogenesis.
AB  - Epithelial cells and other groups of cells acquire a polarity orthogonal to their
      apical-basal axes, referred to as Planar Cell Polarity (PCP). The process by
      which these cells become polarized requires a signaling pathway using Frizzled as
      a receptor. Responding cells sense cues from their environment that provide
      directional information, and they translate this information into cellular
      asymmetry. Most of what is known about PCP derives from studies in the fruit fly,
      Drosophila. We review what is known about how cells translate an unknown signal
      into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate
      processes of convergent extension and cochlear hair-cell development may relate
      to Drosophila PCP signaling.

PMID- 12806030
TI  - Proteins involved in the trafficking and functional synaptic expression of AMPA
      and KA receptors.
AB  - Alpha-amino-3-hydroxy-5-methylisoxazolepropionate receptors (AMPARs) mediate the
      majority of fast synaptic transmission in the mammalian central nervous system,
      play a central role in synapse stabilisation and plasticity, and their prolonged
      activation is potently neurotoxic. The functional roles of kainate receptors
      (KARs) are less well defined but they play a role in some forms of synaptic
      plasticity. Both receptor types have been shown to be highly developmentally and
      activity-dependently regulated and their functional synaptic expression is under
      tight cellular regulation. The molecular and cellular mechanisms that regulate
      the synaptic localisation and functional expression of AMPARs and KARs are
      objects of concerted research. There has been significant progress towards
      elucidating some of the processes involved with the discovery of an array of
      proteins that selectively interact with individual AMPAR and KAR subunits. These
      proteins have been implicated in, among other things, the regulation of post
      translational modification, targeting and trafficking, surface expression, and
      anchoring. The aim of this review is to present an overview of the major
      interacting proteins and suggest how they may fit into the hierarchical series of
      events controlling the trafficking of AMPARs and KARs.

PMID- 12806031
TI  - Cloning approaches for identifying aging and longevity-related genes in mammals.
AB  - Aging is a phenomenon that affects nearly all animal species. Several studies
      using different systems have identified a number of processes thought to
      contribute to the aging phenotype. Many differentially expressed genes have been
      implicated, but the mechanisms governing mammalian aging (and longevity) are not
      yet fully understood, and the list of concerned genes is still incomplete and
      fragmented. Different approaches have been used to clone aging and longevity
      related genes. In this article we review these cloning techniques and discuss
      their advantages and limitations. Further research on the function of these genes
      as well as the network of their protein products will give better insight into
      the aging process as a whole and its associated pathologies.

PMID- 12806032
TI  - Metamorphosis of benthic invertebrate larvae: a sensitive indicator for detection
      of changes in marine environmental quality.
AB  - Many marine coastal ecosystems are threatened by increasing waste discharge, and
      bioassays are needed because chemical and physical tests alone are not sufficient
      to assess potential effects on aquatic biota. In light of the fact that larval
      metamorphosis of benthic invertebrates is usually very sensitive to environmental
      changes, this paper reviews sensitivity comparisons of larval metamorphosis with
      other common bioassays in different species and those in different developmental
      stages of the same species, and it discusses the potential use of larval
      metamorphosis as an indicator of marine environmental quality.

PMID- 12806033
TI  - Human exposure assessment in air pollution systems.
AB  - The air pollution problem can be depicted as a system consisting of several basic
      components: source, concentration, exposure, dose, and adverse effects. Exposure,
      the contact between an agent (e.g., an air pollutant) and a target (e.g., a human
      respiratory tract), is the key to linking the pollution source and health
      effects. Human exposure to air pollutants depends on exposure concentration and
      exposure duration. Exposure concentration is the concentration of a pollutant at
      a contact boundary, which usually refers to the human breathing zone. However,
      ambient concentrations of regulated pollutants at monitoring sites have been
      measured in practice to represent actual exposure. This can be a valid practice
      if the pollutants are ones that are predominantly generated outdoors and if the
      monitoring sites are appropriately selected to reflect where people are. Results
      from many exposure studies indicate that people are very likely to receive the
      greatest exposure to many toxic air pollutants not outside but inside places such
      as homes, offices, and automobiles. For many of these pollutants, major sources
      of exposure can be quite different from major sources of emission. This is
      because a large emission source can have a very small value of exposure
      effectiveness, i.e., the fraction of pollutant released from a source that
      actually reaches the human breathing zone. Exposure data are crucial to risk
      management decisions for setting priorities, selecting cost-effective approaches
      to preventing or reducing risks, and evaluating risk mitigation efforts.
      Measurement or estimate of exposure is essential but often inadequately addressed
      in environmental epidemiologic studies. Exposure can be quantified using direct
      or indirect measurement methods, depending upon the purpose of exposure
      assessment and the availability of relevant data. The rapidly developing battery
      and electronic technologies as well as advancements in molecular biology are
      expected to accelerate the improvement of current methods and the development of
      new methods for future exposure assessment.

PMID- 12806034
TI  - Shorebird use of coastal wetland and barrier island habitat in the Gulf of
      Mexico.
AB  - The Gulf Coast contains some of the most important shorebird habitats in North
      America. This area encompasses a diverse mixture of estuarine and barrier island
      habitats with varying amounts of freshwater swamps and marshes, bottomland
      hardwood forests, and coastal prairie that has been largely altered for rice and
      crawfish production, temporary ponds, and river floodplain habitat. For the
      purposes of this review, discussion is confined to general patterns of shorebird
      abundance, distribution, and macro- and microhabitat use in natural coastal,
      estuarine, and barrier island habitats on the Gulf of Mexico Coast. The following
      geographic regions are considered: Northwestern Gulf (Rio Grande to Louisiana
      Mississippi border), Northeastern Gulf (Mississippi to Florida Keys), and Mexico
      (Rio Grande to Cabo Catoche [Yucatan Strait]). Wintering and migrating shorebirds
      are most abundant along the Gulf Coast in Texas and Tamaulipas, particularly the
      Laguna Madre ecosystem. Other important areas are the Southwest Coast region of
      Florida and the area between Laguna Terminos and Puerto Progresso in Mexico. In
      general, relative abundances of shorebirds increase from north to south, and
      decrease south of the Tropic of Cancer (23 degrees 27' N). Based on bimonthly
      maximum counts within 5 latitudinal bands, the region between 25-30 degrees N is
      used most heavily by wintering and spring migrating birds. Non-vegetated coastal
      wetland habitats associated with bays, inlets and lagoons, particularly tidal
      flats, and sandy beaches are the habitats that appear to be favored by wintering
      and migrating shorebirds. In general, these habitats tend to occur as habitat
      complexes that allow for movement between them in relation to tidal flooding of
      bay-shore habitats. This relationship is particularly important to Piping Plover
      and may be important to others. Although vegetated habitats are used by some
      species, they do not appear to attract large numbers of birds. This habitat is
      most widespread between the Texas-Louisiana border and the Florida Panhandle
      region, but it has not been studied extensively. Shorebird abundance and habitat
      use in this area need to be addressed.

PMID- 12806035
TI  - Vertical distribution of ozone and nitric acid vapor on the Mammoth Mountain,
      eastern Sierra Nevada, California.
AB  - In August and September 1999 and 2000, concentrations of ozone (O3) and nitric
      acid vapor (HNO3) were monitored at an elevation gradient (2184-3325 m) on the
      Mammoth Mountain, eastern Sierra Nevada, California. Passive samplers were used
      for monitoring exposure to tropospheric O3 and HNO3 vapor. The 2-week average O3
      concentrations ranged between 45 and 72 ppb, while HNO3 concentrations ranged
      between 0.06 and 0.52 microg/m3. Similar ranges of O3 and HNO3 were determined
      for 2 years of the study. No clear effects of elevation on concentrations of the
      two pollutants were detected. Concentrations of HNO3 were low and at the
      background levels expected for the eastern Sierra Nevada, while the measured
      concentrations of O3 were elevated. High concentrations of ozone in the study
      area were confirmed with an active UV absorption O3 monitor placed at the Mammoth
      Mountain Peak (September 5-14, 2000, average 24-h concentration of 56 ppb).

PMID- 12806036
TI  - Vertical distribution of ozone and nitrogenous pollutants in an air quality class
      I area, the San Gorgonio wilderness, southern California.
AB  - Information about spatial and temporal distribution of air pollutants is
      essential for better understanding of environmental stresses affecting forests
      and estimation of potential risks associated with air pollutants. Ozone and
      nitrogenous air pollutants were monitored along an elevation gradient in the
      Class I San Gorgonio Wilderness area (San Bernardino Mountains, California, U.S.)
      during the summer of 2000 (mid-June to mid-October). Passive samplers were
      exposed for 2-week periods at six sampling sites located at 300 m intervals
      ranging from 1200 to 2700 m elevation. Elevated concentrations of ozone were
      found in this area with summer 24-h hourly means ranging from 53 to 59 ppb. The
      highest ozone concentrations were detected in the period July 25-August 8,
      reaching values of 64 to 72 ppb expressed as 2-week mean. Passive-sampler ozone
      data did not show a clear relationship with elevation, although during the
      periods with higher ozone levels, ozone concentrations were higher at those sites
      below 2000 m than at sites located above that elevation. All nitrogenous
      pollutants studied showed a consistent decrease of concentrations with elevation.
      Nitrogen dioxide (NO2) levels were low, decreasing with increasing elevation from
      6.4 to 1.5 ppb summer means. Nitric oxide (NO) concentrations were around 1 to 2
      ppb, which is within the range of the detection levels of the devices used.
      Nitric acid (HNO3) vapor concentrations were lower at higher elevations (summer
      means 1.9-2.5 microg m(-3) than at lower elevations (summer means 4.3-5.1 microg
      m(-3). Summer concentrations of ammonia (NH3) were slightly higher than nitric
      acid ranging from 6 microg m(-3) at the lowest site to 2.5 microg m(-3)
      registered at the highest elevation. Since complex interactions between ozone and
      nitrogenous air pollutants have already been described for forests, simultaneous
      information about the distribution of these pollutants is needed. This is
      particularly important in mountain terrain where no reliable models of air
      pollutant distribution exist.

PMID- 12806037
TI  - Developmental and activity dependent regulation of ionotropic glutamate receptors
      at synapses.
AB  - Glutamate receptors mediate the majority of excitatory responses in the central
      nervous system. The establishment and refinement of glutamatergic synaptic
      connections depend on the concerted actions of alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), and kainate (KA) type
      ionotropic glutamate receptors (iGluRs) and G-protein coupled metabotropic
      receptors. While a lot remains to be clarified, the most is known about the
      mechanisms by which the iGluR subtypes are targeted and how this is influenced by
      synaptic activity on both short and long time scales. Changes in their subunit
      compositions are also input specific and developmentally regulated. The
      identification of key molecular components of the postsynaptic density (PSD) and
      novel proteins that influence receptor targeting and clustering have started to
      reveal the underlying molecular mechanisms of the trafficking and targeting of
      iGluRs. Here we discuss the evidence that these basic mechanisms are used during
      developmental synaptic plasticity.

PMID- 12806038
TI  - Wastewater minimization in indirect electrochemical synthesis of
      phenylacetaldehyde.
AB  - Wastewater minimization in phenylacetaldehyde production by using indirect
      electrochemical oxidation of phenylethane instead of the seriously polluting
      traditional chemical process is described in this paper. Results show that high
      current efficiency of Mn(III) and high yield of phenylacetaldehyde can be
      obtained at the same sulfuric acid concentration (60%). The electrolytic mediator
      can be recycled and there will be no waste discharged.

PMID- 12806039
TI  - Carbon reservoirs in temperate South American Nothofagus forests.
AB  - Humans are influencing the global carbon (C) cycle due to the combustion of
      fossil fuels and due to changes in land use management. These activities are
      fostering the manmade greenhouse effect and thus global climate change. Negative
      effects for life on earth are accounted for. Among others the international
      climate debate focused attention on forests and forestry, knowing about their
      considerable influence on global climate change. Whilst the global C budget is
      described fairly well, there is a lack of regional data describing the C
      reservoirs and flows in detail. This has to be constituted especially for forests
      in developing countries. This paper presents an investigation at regional scale
      of the C reservoirs in a South American forest ecosystem. The investigation puts
      emphasis on the area and stand volume estimation and the development of expansion
      and reduction factors. Vegetation types are classified and stratified,
      determining the corresponding areas and estimating the stand volume. Converting
      factors are developed to calculate C in branches and roots as a percentage of
      standing wood measured by inventories.

PMID- 12806041
TI  - The role of high density lipoproteins in thrombosis.
AB  - Lipids and lipoproteins, as well as factors involved in hemostasis and
      thrombosis, play a central role in the pathogenesis of cardio- and
      cerebrovascular disease. In recent years it has become clear that a strong
      association exists between coagulation factors and plasma lipoproteins. Anionic
      phospholipids are necessary for the optimal activity of both pro- and
      anticoagulant enzymatic complexes. Cell membranes have traditionally been
      considered to provide the essential lipid-containing surfaces. However, in light
      of recent studies, plasma lipoproteins are also believed to provide appropriate
      surfaces to support coagulation. While triglyceride-rich lipoproteins and
      oxidized low-density lipoproteins are associated with a procoagulant profile,
      high-density lipoproteins (HDL) may have an anticoagulant effect. This paper
      reviews scientific data on the potential role of HDL as modulator of thrombotic
      processes.

PMID- 12806040
TI  - Epithelial cell-neutrophil interactions in the alimentary tract: a complex dialog
      in mucosal surveillance and inflammation.
AB  - Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and
      intestine, inevitably require the intimate interactions of neutrophils with
      columnar epithelia. The physiologic consequences of such interactions often
      determine endpoint organ function, and for this reason, much recent interest has
      developed in identifying mechanisms and novel targets for the treatment of
      mucosal inflammation. Elegant in vitro model systems incorporating purified human
      neutrophils and human epithelial cells grown in physiologic orientations have
      aided in discovery of new and insightful pathways to define basic inflammatory
      pathways. Here, we will review the recent literature regarding the interactions
      between columnar epithelial cells and neutrophils, with an emphasis on intestinal
      epithelial cells, structural aspects of neutrophil transepithelial migration,
      molecular determinants of neutrophil-epithelial cell interactions, as well as
      modulation of these pathways. These recent studies highlight the dynamic nature
      of these pathways and lend insight into the complexity of treating mucosal
      inflammation.

PMID- 12806042
TI  - Comparison of Artificial Neural Network (ANN) Model Development Methods for
      Prediction of Macroinvertebrate Communities in the Zwalm River Basin in Flanders,
      Belgium.
AB  - Modelling has become an interesting tool to support decision making in water
      management. River ecosystem modelling methods have improved substantially during
      recent years. New concepts, such as artificial neural networks, fuzzy logic,
      evolutionary algorithms, chaos and fractals, cellular automata, etc., are being
      more commonly used to analyse ecosystem databases and to make predictions for
      river management purposes. In this context, artificial neural networks were
      applied to predict macroinvertebrate communities in the Zwalm River basin
      (Flanders, Belgium). Structural characteristics (meandering, substrate type, flow
      velocity) and physical and chemical variables (dissolved oxygen, pH) were used as
      predictive variables to predict the presence or absence of macroinvertebrate taxa
      in the headwaters and brooks of the Zwalm River basin. Special interest was paid
      to the frequency of occurrence of the taxa as well as the selection of the
      predictors and variables to be predicted on the prediction reliability of the
      developed models. Sensitivity analyses allowed us to study the impact of the
      predictive variables on the prediction of presence or absence of
      macroinvertebrate taxa and to define which variables are the most influential in
      determining the neural network outputs.

PMID- 12806044
TI  - Ecosystem management and ecological modeling.
AB  - It is the intention of this paper to demonstrate that environmental technology
      must be supplemented by other tools to be able to solve environmental problems
      properly. Five cases are used to illustrate the possibilities of ecological
      engineering, a new engineering field based on ecology, as chemical engineering is
      based on chemistry. It encompasses restoration of ecosystems, utilization of
      ecosystems to the benefit of both mankind and nature, construction of ecosystems,
      and ecologically sound planning of ecosystems from a holistic point of view.
      Ecological engineering requires a good knowledge of the system properties of
      ecosystems to be able to fully utilize the possibilities that ecosystem
      management offers. Models reflecting the ecosystem properties are furthermore
      needed to be able to quantify the effects of the ecological engineering solutions
      to the environmental problems. This is clearly demonstrated in two of the five
      case studies presented in the paper.

PMID- 12806045
TI  - A throughfall collection method using mixed bed ion exchange resin columns.
AB  - Measurement of ionic deposition in throughfall is a widely used method for
      measuring deposition inputs to the forest floor. Many studies have been
      published, providing a large database of throughfall deposition inputs to
      forests. However, throughfall collection and analysis is labor intensive and
      expensive because of the large number of replicate collectors needed and because
      sample collection and chemical analyses are required on a stochastic
      precipitation event-based schedule. Therefore we developed and tested a
      throughfall collector system using a mixed bed ion exchange resin column. We
      anticipate that this method will typically require only one to three samplings
      per year. With this method, bulk deposition and bulk throughfall are collected by
      a funnel or snow tube and ions are retained as the solution percolates through
      the resin column. Ions retained by the resin are then extracted in the same
      column with 2 N KCl and analyzed for nitrate and ammonium. Deposition values in
      throughfall from conventional throughfall solution collectors and colocated ion
      exchange samplers were not significantly different during consecutive 3- and 4
      month exposure periods at a high (Camp Paivika; >35 kg N ha(-1) year(-1)) and a
      low deposition (Barton Flats; 5-9 kg N ha(-1) year(-1)) site in the San
      Bernardino Mountains in southern California. N deposition in throughfall under
      mature pine trees at Camp Paivika after 7 months of exposure was extremely high
      (87 and 92 kg ha-1 based on the two collector types) compared to Barton Flats (11
      and 13 kg ha(-1)). A large proportion of the N deposited in throughfall at Camp
      Paivika occurred as fog drip, demonstrating the importance of fog deposition as
      an input source of N at this site. By comparison, bulk deposition rates in open
      areas were 5.1 and 5.4 kg ha(-1) at Camp Paivika based on the two collector
      types, and 1.9 and 3.0 kg ha(-1) at Barton Flats.

PMID- 12806048
TI  - Polychlorinated alkanes in fish from Norwegian freshwater.
AB  - Short-chain polychlorinated alkanes (sPCAs) have been measured in freshwater fish
      samples from different lakes all over Norway and from the Norwegian Arctic. The
      analyses were performed with high-resolution GC coupled to high-resolution MS in
      electron capture negative ion mode. The species investigated were trout, Arctic
      char, and burbot (Lota lota). Muscle tissue in the lake trout and Arctic char,
      and liver in burbot, were selected for analyses because of their high lipid
      content. SigmasPCA concentration ranged from 108 to 3700 ng/g fat. The highest
      value was found in the south of Norway near an industrial area.

PMID- 12806049
TI  - Development of a statistical model for estimating spatial and temporal ambient
      ozone patterns in the Sierra Nevada, California.
AB  - Statistical approaches for modeling spatially and temporally explicit data are
      discussed for 79 passive sampler sites and 9 active monitors distributed across
      the Sierra Nevada, California. A generalized additive regression model was used
      to estimate spatial patterns and relationships between predicted ozone exposure
      and explanatory variables, and to predict exposure at nonmonitored sites. The
      fitted model was also used to estimate probability maps for season average ozone
      levels exceeding critical (or subcritical) levels in the Sierra Nevada region.
      The explanatory variables--elevation, maximum daily temperature, and
      precipitation and ozone level at closest active monitor--were significant in the
      model. There was also a significant mostly east-west spatial trend. The between
      site variability had the same magnitude as the error variability. This seems to
      indicate that there still exist important site features not captured by the
      variables used in the analysis and that may improve the accuracy of the
      predictive model in future studies. The fitted model using robust techniques had
      an overall R2 value of 0.58. The mean standard deviation for a predicted value
      was 6.68 ppb.

PMID- 12806050
TI  - A new all-season passive sampling system for monitoring H2S in air.
AB  - A new Maxxam All-Season Passive Sampling system for monitoring H2S in air has
      been developed. This passive sampling system employs the same approaches as the
      Maxxam All-Season Passive Sampling Systems for monitoring SO2, NO2, and O3
      reported previously. This system has been extensively tested in the lab
      (temperature from -20 to 20 degrees C, relative humidity from 30 to 84%, and wind
      speed from 0.5 to 150 cm/s) and validated in field studies. Comparing
      measurements obtained with the use of the new passive sampling system with
      equivalent measurement with the use of an active filter pack H2S sampler yielded
      an accuracy of greater than 85%. The new H2S passive sampling system can be used
      to measure ambient H2S concentrations ranging from 0.02 to 7 ppb based on a 1
      month exposure period. There is no significant interference found from other
      sulfur compounds in air. This system has been used in many air monitoring
      projects.

PMID- 12806051
TI  - Lipid-derived mediators in endogenous anti-inflammation and resolution: lipoxins
      and aspirin-triggered 15-epi-lipoxins.
AB  - It is well appreciated that lipid-derived mediators play key roles in
      inflammation and many other physiologic responses where multicellular processes
      are involved. Among them, lipoxins (LX) and aspirin-triggered LX (ATL) evoke
      actions of interest in a range of physiologic and pathophysiologic processes, and
      these two series have emerged as founding members of the first class of
      lipid/chemical mediators "switched on" in the resolution phase of an inflammatory
      reaction. These unique compounds possess a trihydroxytetraene structure and are
      both structurally and functionally distinct among the many groups of lipid
      derived bioactive mediators. LXA4 and 15-epi-LXA4 (a member of the ATL series)
      display leukocyte-selective actions that enable them to serve as endogenous "stop
      signals" in multicellular events in that they modulate adherence, transmigration,
      and chemotaxis. Both LXA4 and 15-epi-LXA elicit these responses via a G protein
      coupled receptor (GPCR), termed ALXR, identified in human and murine tissues.
      Among eicosanoids, ALXR is stereoselective for LXA4 (5S,6R,15S-trihydroxy-7,9,13-
      trans-11-cis-eicosatetraenoic acid). Its aspirin-triggered 15 R epimer (15-epi
      LXA4) and their bioactive stable analogs act in the subnanomolar to nanomolar
      range in human cellular systems and murine models of acute inflammation and
      reperfusion. ALXR also has the ability to interact with a wide panel of small
      peptides that give different signaling responses in vitro than LXA4 or its
      analogs, suggesting that ALXR is capable of serving as a multirecognition
      receptor in immune responses. Characterization of ALXR and development of
      metabolically stable LX and ATL analogs that are mimetics rapidly advanced our
      appreciation of the mechanism of LX actions and the potential utility of these
      counter-regulatory biocircuits in the quest to control local inflammatory events.
      In this on-line update, LX and ATL biosynthesis and the LXA4 specific receptor,
      termed ALXR, are reviewed with a focus on their roles in inflammation and
      resolution with respect to pharmacology, molecular biology, and signal
      transduction in several cell types and animal models investigated thus far.

PMID- 12806052
TI  - Structural predestination of individual diversity in the course and severity of
      infectious diseases.
AB  - Infectious diseases can be manifested by a spectrum of clinical signs and
      resultant clinical courses that range from acute to chronic and possible
      persistence in the victim in a latent form. Until recently, the origins of this
      kind of biodiversity were poorly understood, but advances in immunology-
      especially in identifying the constitutional mechanisms of immunity--have
      contributed to our understanding of the origins of biodiversity in infectious
      diseases. Infectious diseases affect only focal areas in the affected organisms,
      and the amounts and distribution of infectious lesions vary from patient to
      patient. In a population attacked by an infectious agent, individuals can be
      conveniently divided into three categories: totally resistant organisms which
      contain no susceptible structures and are not affected; mildly susceptible
      organisms in which a few foci appear and in which the infection runs a benign
      course; organisms in which the number of constitutionally susceptible structures
      is high and the infectious process develops in a severe form. The diversity is
      determined by the differences in susceptibility of various parts of the organism
      under consideration.

PMID- 12806053
TI  - Attentional phenotypes for the analysis of higher mental function.
AB  - We outline a strategy to relate normal cognitive processes to candidate genes.
      First, brain imaging is used to specify a cognitive process "attention" in terms
      of the neural networks involved. Next, evidence is presented showing that the
      operation of each network involves a dominant neuromodulator. Then we discuss
      development of a task designed to measure the efficiency of each network in
      normal individuals and consider evidence on the independence, reliability, and
      heritability of the networks. DNA from cheek swabs of subjects who performed the
      task are then used to examine candidate polymorphisms in genes related to the
      transmitters. We then examine the ability of these candidate alleles to predict
      the efficiency of relevant networks. This process has demonstrated that candidate
      genes are related to specific networks of attention to a greater degree than to
      overall performance as measured by reaction time and accuracy. These findings
      require replication and possible extension to other cognitive processes.

PMID- 12806054
TI  - Receptor-mediated gene delivery.
AB  - Receptor-mediated gene delivery capitalises on the presence of specific cell
      surface molecules for DNA uptake into cells and represents a particularly
      appealing approach for targeting vector DNA to specific cell types in vivo and in
      vitro. Various ligand/DNA and antibody/DNA transfer complexes were generated
      that, following binding to cells, are internalised and reach the endosomal
      compartment. Vector complexes contain endosomolytic components that ensure vector
      release from the endosome and translocation of vector DNA into the nucleus where
      transcription occurs. Thus, receptor-mediated gene delivery encompasses several
      critical steps that must be considered when designing and applying such vector
      systems.

PMID- 12806055
TI  - Stress-induced premature senescence or stress-induced senescence-like phenotype:
      one in vivo reality, two possible definitions?
AB  - No consensus exists so far on the definition of cellular senescence. The
      narrowest definition of senescence is irreversible growth arrest triggered by
      telomere shortening counting cell generations (definition 1). Other authors gave
      an enlarged functional definition encompassing any kind of irreversible arrest of
      proliferative cell types induced by damaging agents or cell cycle deregulations
      after overexpression of proto-oncogenes (definition 2). As stress increases, the
      proportion of cells in "stress-induced premature senescence-like phenotype"
      according to definition 1 or "stress-induced premature senescence," according to
      definition 2, should increase when a culture reaches growth arrest, and the
      proportion of cells that reached telomere-dependent replicative senescence due to
      the end-replication problem should decrease. Stress-induced premature senescence
      like phenotype and telomere-dependent replicatively senescent cells share basic
      similarities such as irreversible growth arrest and resistance to apoptosis,
      which may appear through different pathways. Irreversible growth arrest after
      exposure to oxidative stress and generation of DNA damage could be as efficient
      in avoiding immortalisation as "telomere-dependent" replicative senescence.
      Probabilities are higher that the senescent cells (according to definition 2)
      appearing in vivo are in stress-induced premature senescence rather than in
      telomere-dependent replicative senescence. Examples are given suggesting these
      cells affect in vivo tissue (patho)physiology and aging.

PMID- 12806056
TI  - Protein repair and degradation during aging.
AB  - Cellular aging is characterized by a build-up of oxidatively modified proteins.
      The steady-state level of oxidized proteins depends on the balance between the
      rate of protein oxidative damage and the rates of protein degradation and repair.
      Therefore, the accumulation of oxidized protein with age can be due to increased
      protein damage, decreased oxidized protein degradation and repair, or the
      combination of both mechanisms. The proteasomal system is the major intracellular
      proteolytic pathway implicated in the degradation of oxidized protein, and the
      peptide methionine sulfoxide reductase catalyzes the reduction of methionine
      sulfoxide (i.e., oxidized methionine) to methionine within proteins. A short
      summary on protein oxidative damage and oxidized protein degradation is given,
      and evidence for a decline of proteasome function with age is presented.
      Arguments for the implication of peptide methionine sulfoxide reductase in the
      age-related accumulation of oxidized protein are also discussed.

PMID- 12806057
TI  - Use of thermodynamic orientors to assess the efficiency of ecosystems: a case
      study in the lagoon of Venice.
AB  - So-called orientors have been introduced at the interface between ecology and
      thermodynamics. Two have been chosen here to compare the characteristics of five
      ecological systems: exergy, which is related to the degree of organization of a
      system and represents the biogeochemical energy of a system, and emergy, which is
      defined as the total amount of solar energy directly or indirectly required to
      generate a product or a service. They represent two complementary aspects of a
      system: the actual state and the past work needed to reach that state. The ratio
      of exergy to the emergy flow indicates the efficiency of an ecosystem in
      producing or maintaining its organization. The main system under study is a
      portion of the Venice Lagoon, which is used as a fish farming basin. Four other
      aquatic ecosystems were considered for comparison. Results show that the
      ecosystem within the Venice Lagoon is the one with the highest efficiency in
      transforming the available inputs in organization of the system. This fact is due
      to human intervention, which is very limited but also very effective.

PMID- 12806058
TI  - In vitro exposure of porcine ovarian follicular cells to PCB 153 alters steroid
      secretion but not their viability--preliminary study.
AB  - In our previous paper, we demonstrated that porcine follicles collected during
      the early stage of development are the most sensitive to the toxic action of
      polychlorinated biphenyl 153 (PCB 153). Follicles of this type were collected to
      test the effect of PCB 153 on cell steroidogenesis and viability. Cocultures of
      granulosa and theca cells were grown in M199 medium at 37 degrees C. Control
      cultures were maintained in that medium alone, while experimental ones were
      supplemented with PCB 153 at doses of 5, 10, 50, and 100 ng/ml. After 48, 96, and
      144 h, media were collected for steroid analysis and cell viability was measured
      using an LDH (lactate dehydrogenase activity) cytotoxicity test. A 2-day exposure
      of follicular cells to all the investigated doses of PCB 153 caused a
      statistically significant decrease in progesterone (P4) secretion, while in doses
      of 50 and 100 ng/ml there was also a decrease in testosterone (T) secretion. No
      effect on estradiol (E2) secretion was observed. The observed decrease in P4 and
      T secretion, and lack of any statistically significant effect on E2 secretion by
      cells from small follicles exposed for 48 h to PCB, suggests that PCB 153 acts
      before P4 formation. Longer exposures caused an increase in P4 secretion, with a
      concomitant drastic decrease in T secretion and a tendency to decrease the E2
      secretion, suggesting inhibition of P450 17 alpha hydroxysteroid dehydrogenase,
      an enzyme that converts P4 to T. The observed PCB 153-induced increase in P4
      secretion by cells collected from small antral follicles, with a concomitant
      decrease in E2 secretion, accounts for the induction of luteinization and, in
      this case, inhibition of aromatization process in the follicles. However, in all
      doses tested and at all times of exposure, PCB 153 had no effect on cell
      viability. These findings suggest different time of exposure-dependent action of
      PCB 153 on particular steps of steroidogenesis but not action on cell viability.
      These results should be considered preliminary, pending confirmation by other
      studies.

PMID- 12806060
TI  - Simulated impacts of juvenile mortality on Gulf of Mexico sturgeon populations.
AB  - We used an age-structured computer model to assess the impact of changes in
      juvenile mortality on the Gulf of Mexico sturgeon population in the Suwannee
      River, Florida. We simulated population trends under four levels of annual
      juvenile mortality (20, 25, 30, and 35%). As the rate of mortality increased,
      population size decreased, and rates of population growth shifted from positive
      to negative. Our models indicated that juvenile survival is important to the
      success of gulf sturgeon populations, and mortality estimates are needed to
      predict population viability. We suggest that life history studies in estuaries
      should be conducted, and bycatch rates for commercial fisheries should be
      quantified to aid in the management and conservation of gulf sturgeon.

PMID- 12806061
TI  - Reactions among indoor pollutants.
AB  - This paper reviews recent studies in the field of "indoor chemistry"--reactions
      among indoor pollutants. Advances have occurred in a number of areas. A mouse
      bioassay procedure has shown that ozone/terpene reactions produce products that
      are more irritating than their precursors, although the agents responsible for
      the deleterious effects remain to be determined. Indoor ozone/terpene reactions
      have been demonstrated to produce hydroxyl radicals, hydrogen peroxide, sub
      micron particles, and ultrafine particles. New analytical techniques such as
      LC/MS and thermal desorption mass spectrometry have greatly improved our
      knowledge of the condensed-phase species associated with such particles. Indeed,
      the latter approach has identified a number of short-lived or thermally labile
      species, including organic hydroperoxides, peroxy-hemiacetals, and secondary
      ozonides, which would be missed by more conventional techniques. Investigators
      are making inroads into the poorly understood area of indoor heterogeneous
      chemistry. Systems studied include ozone/HVAC components, ozone/paint, and
      ozone/carpets. Another heterogeneous process that has been further examined is
      the indoor formation of nitrous acid through NO2/surface chemistry. Emissions
      from indoor sources that contribute to, or are altered by, indoor chemistry have
      also received attention. Researchers have expanded our awareness of reactive
      chemicals that can emanate from wood coatings and other products commonly used
      indoors. In a related vein, a number of recent investigations have shown that
      emissions from materials can be significantly altered by indoor chemistry. On the
      theoretical side, an outdoor atmospheric chemistry model has been modified for
      use as an indoor air model, the effects of ventilation rates on indoor chemistry
      have been simulated, and initial steps have been taken in applying computational
      fluid dynamics (CFD) methods to indoor chemistry.

PMID- 12806062
TI  - Proceedings of the international symposium on passive sampling of gaseous air
      pollutants in ecological effects research: preface.

PMID- 12806063
TI  - Introduction to Maxxam all-season passive sampling system and principles of
      proper use of passive samplers in the field study.
AB  - Maxxam all-season passive sampling system (PASS) is introduced in this paper. The
      PASS can be used to quantitatively and accurately monitor SO2, NO2, O3, and H2S
      in air in all weather conditions with flexible exposure times from several hours
      to several months. The air pollution detection limits of PASS are very low. They
      can be from sub ppb to ppt levels. The principles of proper use of passive
      samplers in the field study are discussed by using the PASS as an example.

PMID- 12806064
TI  - The use of a new passive sampler for ozone and nitrogen oxides monitoring in
      ecological effects research.
AB  - A simple, cost-effective diffusive sampler is described that is suitable for
      measuring parts per billion (ppb) levels of ozone and nitrogen oxides. The
      diffusive sampler makes use of nitrite for ozone determination whereas for
      nitrogen oxides and nitrogen dioxide an active carbon tissue impregnated with
      sodium carbonate is used. Nitrate and nitrite, the formation of which is
      proportional to the pollutant concentration and sampling duration, are the two
      species analysed, respectively. Diffusion tubes have the advantage of being a low
      cost, convenient way of mapping spatial distributions and investigating long
      term trends of ozone and nitrogen oxides. The method is extremely useful for
      assessing long-term concentrations such as the annual mean for nitrogen oxides,
      as required by the Daughter Directive 1999/30/EC. Field tests to validate the
      method have been carried out at an urban background location with co-located
      passive samplers and continuous measurements of O3 and NOx. An application in
      ecological effects monitoring for ozone is also presented.

PMID- 12806065
TI  - Spatial distribution of tropospheric ozone in national parks of California:
      interpretation of passive-sampler data.
AB  - The National Park Service (NPS) has tested and used passive ozone samplers for
      several years to get baseline values for parks and to determine the spatial
      variability within parks. Experience has shown that the Ogawa passive samplers
      can provide +/-10% accuracy when used with a quality assurance program consisting
      of blanks, duplicates, collocated instrumentation, and a standard operating
      procedure that carefully guides site operators. Although the passive device does
      not meet EPA criteria as a certified method (mainly, that hourly values be
      measured), it does provide seasonal summed values of ozone. The seasonal ozone
      concentrations from the passive devices can be compared to other monitoring to
      determine baseline values, trends, and spatial variations. This point is
      illustrated with some kriged interpolation maps of ozone statistics. Passive
      ozone samplers were used to get elevational gradients and spatial distributions
      of ozone within a park. This was done in varying degrees at Mount Rainier,
      Olympic, Sequoia-Kings Canyon, Yosemite, Joshua Tree, Rocky Mountain, and Great
      Smoky Mountains national parks. The ozone has been found to vary by factors of 2
      and 3 within a park when average ozone is compared between locations. Specific
      examples of the spatial distributions of ozone in three parks within California
      are given using interpolation maps. Positive aspects and limitations of the
      passive sampling approach are presented.

PMID- 12806066
TI  - Atmospheric deposition of nitrogen and sulphur compounds in the Czech Republic.
AB  - Estimates of dry and wet deposition of nitrogen and sulphur compounds in the
      Czech Republic for the years 1994 and 1998 are presented. Deposition has been
      estimated from monitored and modeled concentrations in the atmosphere and in
      precipitation, where the most important acidifying compounds are sulphur dioxide,
      nitrogen oxides, ammonia, and their reaction products. Measured atmospheric
      concentrations of SO2, NOx, NH3, and aerosol particles (SO4(2-), NO3-, and NH4+),
      along with measured concentrations of SO4(2-), NO3-, and NH4+ in precipitation,
      weighted by precipitation amounts, were interpolated with Kriging technique on a
      10- x 10-km grid covering the whole Czech Republic. Wet deposition was derived
      from concentration values for SO4(2-), NO3-, and NH4+ in precipitation and from
      precipitation amounts. Dry deposition was derived from concentrations of gaseous
      components and aerosol in the air, and from their deposition velocities. A
      multiple resistance model was used for calculation of SO2, NOx, and NH3
      deposition velocities. Deposition velocities of particles were parameterized. It
      was estimated that the annual average deposition of SOx in the Czech Republic
      decreased from 1384 to 1027 mol H + ha(-1) a(-1) between 1994 and 1998. The
      annual average NOy deposition was estimated to be 972 and 919 mol H + ha(-1) a(
      1) in 1994 and 1998, respectively. The annual average NHx deposition was
      estimated to be 887 mol H+ ha(-1) a(-1) and 779 mol H + ha(-1) a(-1) in 1994 and
      1998, respectively. It was estimated that the annual average of the total
      potential acid deposition decreased from 3243 to 2725 mol H + ha(-1) a(-1)
      between 1994 and 1998. Sulphur compounds (SOx) contributed about 38%, oxidized
      nitrogen species (NOy) 34%, and reduced nitrogen species (NHx) 28% to the total
      potential acid deposition in 1998. The wet deposition contributed 42% to the
      total potential acid deposition in 1998.

PMID- 12806067
TI  - An approach to balancing the positive and negative effects of elevated nitrogen
      oxides in the lower atmosphere on terrestrial plants.
AB  - Elevated NOx in the lower atmosphere has three major effects on terrestrial
      plants. On the one hand, it causes an increase in surface ozone concentration.
      This reduces plant growth rate. On the other hand, elevated NOx causes an
      increase in the flux of oxidized N compounds from the atmosphere to the land
      surface. This plays a dual role in the life of terrestrial plants. Additional N
      in soils stimulates plant growth (N-fertilization effect), whereas soil
      acidification may negatively affect plants. A simple empirical model for
      calculating the overall effect of anthropogenic increase in NOx level has been
      developed. The model is based on experimental "cause-response" data presented in
      world scientific literature. Calculations showed that at the large scale, among
      the above-mentioned changes, elevated O3 plays a major and negative role in plant
      life. Its negative effect on plants is partly compensated by N fertilization in
      unmanaged ecosystems. Such compensation appears to be negligible in agricultural
      lands. There are vast territories in Euro--Asia--for instance, a territory of
      Russia--in which acid atmospheric deposition has no significant effect on
      terrestrial plants.

PMID- 12806068
TI  - Bermudagrass management in the Southern Piedmont U.S. IV. Soil surface nitrogen
      pools.
AB  - The fate of nitrogen (N) applied in forage-based agricultural systems is
      important for understanding the long-term production and environmental impacts of
      a particular management strategy. We evaluated the factorial combination of three
      types of N fertilization (inorganic, crimson clover [Trifolium incarnatum L.]
      cover crop plus inorganic, and chicken [Gallus gallus] broiler litter pressure
      and four types of harvest strategy (unharvested forage, low and high cattle [Bos
      Taurus] grazing pressure, and monthly haying in summer) on surface residue and
      soil N pools during the first 5 years of 'Coastal' bermudagrass (Cynodon dactylon
      [L.] Pers.) management. The type of N fertilization used resulted in small
      changes in soil N pools, except at a depth of 0 to 2 cm, where total soil N was
      sequestered at a rate 0.2 g x kg(-1) x year(-1) greater with inorganic
      fertilization than with other fertilization strategies. We could account for more
      of the applied N under grazed systems (76-82%) than under ungrazed systems (35
      71%). As a percentage of applied N, 32 and 48% were sequestered as total soil N
      at a depth of 0 to 6 cm when averaged across fertilization strategies under low
      and high grazing pressures, respectively, which was equivalent to 6.8 and 10.3 g
      x m(-2) x year(-1). Sequestration rates of total soil N under the unharvested
      forage and haying strategies were negligible. Most of the increase in total soil
      N was at a depth of 0 to 2 cm and was due to changes in the particulate organic N
      (PON) pool. The greater cycling of applied N into the soil organic N pool with
      grazed compared with ungrazed systems suggests an increase in the long-term
      fertility of soil.

PMID- 12806069
TI  - Nitrogen use and carbon sequestered by corn rotations in the northern corn belt,
      U.S.
AB  - Diversified crop rotation may improve production efficiency, reduce fertilizer
      nitrogen (N) requirements for corn (Zea mays L.), and increase soil carbon (C)
      storage. Objectives were to determine effect of rotation and fertilizer N on soil
      C sequestration and N use. An experiment was started in 1990 on a Barnes clay
      loam (U.S. soil taxonomy: fine-loamy, mixed, superactive, frigid Calcic
      Hapludoll) near Brookings, SD. Tillage systems for corn-soybean ( Glycine max
      [L.] Merr.) rotations were conventional tillage (CS) and ridge tillage (CSr).
      Rotations under conventional tillage were continuous corn (CC), and a 4-year
      rotation of corn-soybean-wheat ( Triticum aestivum L.) companion-seeded with
      alfalfa ( Medicago sativa L.)-alfalfa hay (CSWA). Additional treatments included
      plots of perennial warm season, cool season, and mixtures of warm and cool season
      grasses. N treatments for corn were corn fertilized for a grain yield of 8.5 Mg
      ha(-1) (highN), of 5.3 Mg ha(-1) (midN), and with no N fertilizer (noN). Total
      (1990-2000) corn grain yield was not different among rotations at 80.8 Mg ha(-1)
      under highN. Corn yield differences among rotations increased with decreased
      fertilizer N. Total (1990-2000) corn yields with noN fertilizer were 69 Mg ha-1
      under CSWA, 53 Mg ha(-1) under CS, and 35 Mg ha(-1) under CC. Total N attributed
      to rotations (noN treatments) was 0.68 Mg ha(-1) under CSWA, 0.61 Mg ha(-1) under
      CS, and 0.28 Mg ha(-1) under CC. Plant carbon return depended on rotation and N.
      In the past 10 years, total C returned from above- ground biomass was 29.8 Mg ha(
      1) under CC with highN, and 12.8 Mg ha(-1) under CSWA with noN. Soil C in the top
      15 cm significantly increased (0.7 g kg(-1)) with perennial grass cover, remained
      unchanged under CSr, and decreased (1.7 g kg(-1)) under CC, CS, and CSWA. C to N
      ratio significantly narrowed (-0.75) with CSWA and widened (0.72) under grass.
      Diversified rotations have potential to increase N use efficiency and reduce
      fertilizer N input for corn. However, within a corn production system using
      conventional tillage and producing (averaged across rotation and N treatment)
      about 6.2-Mg ha(-1) corn grain per year, we found no gain in soil C after 10
      years regardless of rotation.

PMID- 12806070
TI  - Biomechanics of heading a soccer ball: implications for player safety.
AB  - To better understand the risk and safety of heading a soccer ball, the author
      created a set of simple mathematical models based upon Newton's second law of
      motion to describe the physics of heading. These models describe the player, the
      ball, the flight of the ball before impact, the motion of the head and ball
      during impact, and the effects of all of these upon the intensity and the
      duration of acceleration of the head. The calculated head accelerations were
      compared to those during presumably safe daily activities of jumping, dancing,
      and head nodding and also were related to established criteria for serious head
      injury from the motor vehicle crash literature. The results suggest heading is
      usually safe but occasionally dangerous, depending on key characteristics of both
      the player and the ball. Safety is greatly improved when players head the ball
      with greater effective body mass, which is determined by a player"s size,
      strength, and technique. Smaller youth players, because of their lesser body
      mass, are more at risk of potentially dangerous headers than are adults, even
      when using current youth size balls. Lower ball inflation pressure reduces risk
      of dangerous head accelerations. Lower pressure balls also have greater "touch"
      and "playability", measured in terms of contact time and contact area between
      foot and ball during a kick. Focus on teaching proper technique, the re-design of
      age-appropriate balls for young players with reduced weight and inflation
      pressure, and avoidance of head contact with fast, rising balls kicked at close
      range can substantially reduce risk of subtle brain injury in players who head
      soccer balls.

PMID- 12806071
TI  - Accumulation of deficits as a proxy measure of aging.
AB  - This paper develops a method for appraising health status in elderly people. A
      frailty index was defined as the proportion of accumulated deficits (symptoms,
      signs, functional impairments, and laboratory abnormalities). It serves as an
      individual state variable, reflecting severity of illness and proximity to death.
      In a representative database of elderly Canadians we found that deficits
      accumulated at 3% per year, and show a gamma distribution, typical for systems
      with redundant components that can be used in case of failure of a given
      subsystem. Of note, the slope of the index is insensitive to the individual
      nature of the deficits, and serves as an important prognostic factor for life
      expectancy. The formula for estimating an individual's life span given the
      frailty index value is presented. For different patterns of cognitive impairments
      the average within-group index value increases with the severity of the cognitive
      impairment, and the relative variability of the index is significantly reduced.
      Finally, the statistical distribution of the frailty index sharply differs
      between well groups (gamma distribution) and morbid groups (normal distribution).
      This pattern reflects an increase in uncompensated deficits in impaired
      organisms, which would lead to illness of various etiologies, and ultimately to
      increased mortality. The accumulation of deficits is as an example of a
      macroscopic variable, i.e., one that reflects general properties of aging at the
      level of the whole organism rather than any given functional deficiency. In
      consequence, we propose that it may be used as a proxy measure of aging.

PMID- 12806072
TI  - Practical success of biomanipulation using filter-feeding Fish to control
      cyanobacteria blooms: a synthesis of decades of research and application in a
      subtropical hypereutrophic lake.
AB  - Lake Donghu is a 32-km2 shallow, subtropical lake near the Yangtze River (P.R.
      China) that has experienced dramatic changes in the past five decades. These
      changes include: (1) a trophic state change from mesotrophy to hypertrophy; (2)
      dense blooms of cyanobacteria during every summer from the 1970s to 1984; (3) a
      cessation of blooms starting in 1985, with no recurrence; and (4) an increase,
      coincident with bloom declines, in the production of silver and bighead carp
      (filter-feeders) by more than tenfold. There are several possible explanations
      for the disappearance of blooms, including changes in nutrient concentrations,
      increased zooplankton grazing, and increased grazing on algae by fish. The long
      term data suggest that changes in nutrients or in zooplankton were not important,
      but that the remarkably increased fish densities might have played the key role.
      To test this hypothesis, in situ enclosure experiments were conducted in three
      years. The main conclusions are as follows: (1) an increased stocking of the lake
      with carp played a decisive role in the elimination of cyanobacteria blooms; (2)
      both silver and bighead carp can eliminate cyanobacteria blooms directly by
      grazing; (3) zooplankton cannot suppress the blooms; and (4) the lake still is
      vulnerable to the outbreak of blooms, should fish grazing decline. The critical
      biomass of carp is approximately 50 g m3. The results suggest the applicability
      of a new food-web manipulation (increased stocking with filter-feeding fish) for
      controlling cyanobacteria blooms in hypereutrophic lakes. The approach differs
      from traditional biomanipulation in Europe and North America, where piscivores
      are added to control planktivores, and this in turn increases zooplankton and
      decreases algae. The new biomanipulation method is being used or being tested to
      counteract cyanobacteria blooms in many Chinese lakes such as Lake Dianchi in
      Yunnan Province, Lake Chaohu in Anhui Province, and Lake Taihu in Jiangsu
      Province. The method has great potential as an important component of an
      integrated approach to counteract cyanobacteria blooms, especially in lakes where
      nutrient inputs cannot be reduced sufficiently, and where zooplankton cannot
      effectively control phytoplankton production.

PMID- 12806074
TI  - Assessment of heart disease using fuzzy classification techniques.
AB  - In this paper we discuss the classification results of cardiac patients of
      ischemical cardiopathy, valvular heart disease, and arterial hypertension, based
      on 19 characteristics (descriptors) including ECHO data, effort testings, and age
      and weight. In this order we have used different fuzzy clustering algorithms,
      namely hierarchical fuzzy clustering, hierarchical and horizontal fuzzy
      characteristics clustering, and a new clustering technique, fuzzy hierarchical
      cross-classification. The characteristics clustering techniques produce fuzzy
      partitions of the characteristics involved and, thus, are useful tools for
      studying the similarities between different characteristics and for essential
      characteristics selection. The cross-classification algorithm produces not only a
      fuzzy partition of the cardiac patients analyzed, but also a fuzzy partition of
      their considered characteristics. In this way it is possible to identify which
      characteristics are responsible for the similarities or dissimilarities observed
      between different groups of patients.

PMID- 12806073
TI  - Restructuring of the electricity industry and environmental issues: a California
      research program.
AB  - As part of the restructuring of the electricity industry in many states, public
      benefits funding has emerged as a primary mechanism for supporting social
      benefits such as energy efficiency and research and development (RD). In
      California, a Public Interest Energy Research (PIER) Program was established to
      "conduct public interest energy research that seeks to improve the quality of
      life for California"s citizens by providing environmentally sound, safe,
      reliable, and affordable energy services and products. PIER includes the full
      range of research, development, and demonstration activities that will advance
      science or technology not adequately provided by competitive and regulated
      markets." The PIER Program is comprised of six PIER Program funding areas,
      including the Energy-Related Environmental Research. The overall mission of the
      Energy-Related Environmental Research is to "Develop cost-effective approaches to
      evaluating and resolving environmental effects of energy production, delivery,
      and use in California, and explore how new energy applications and products can
      solve environmental problems." This paper describes the process used in
      developing these approaches and identifies a set of environmental issues that the
      State plans to evaluate.

PMID- 12806075
TI  - Air pollution and forest health: establishing cause and effect in the forest.

PMID- 12806076
TI  - Nicotinic receptor activity alters synaptic plasticity.

PMID- 12806077
TI  - The evolution of the neural basic Helix-Loop-Helix proteins.
AB  - Basic Helix-Loop-Helix (bHLH) transcription factors control various aspects of
      the formation of the nervous system in the metazoans. In Drosophila some bHLH
      (such as the achaete-scuteatonal, and amos genes) act as proneural genes,
      directing ectodermal cells toward a neural fate. Their vertebrate orthologs,
      however, probably do not assume such a neural determination function, but rather
      control the decision made by neural precursors to generate neurons and not glial
      cells, as well as the progression of neuronal precursors toward differentiation
      into mature neurons. The proneural function of Drosophila bHLH genes may be an
      innovation that occurs in the evolutive lineage that leads to arthropods. In
      addition, although neural bHLH appear to be involved in the specification of
      neuronal identities, they probably do not confer by themselves neuronal type
      specific properties to the cells. Rather, neural bHLH allow neural cells to
      correctly interpret specification and positional cues provided by other factors.
      Although bHLH genes are often expressed in complementary subsets of neural cells
      and/or expressed sequentially in those cells, the coding regions of the various
      neural bHLH appear largely interchangeable. We propose that the specific
      expression patterns have been acquired, following gene duplications, by
      subfunctionalization, i.e., the partitioning of ancestral expression patterns
      among the duplicates and, by extension, we propose that subfunctionalization is a
      key process to understand the evolution of neural bHLH genes.

PMID- 12806078
TI  - Retention and internal loading of phosphorus in shallow, eutrophic lakes.
AB  - This paper gives a general overview of the nature and important mechanisms behind
      internal loading of phosphorus (P), which is a phenomenon appearing frequently in
      shallow, eutrophic lakes upon a reduction of the external loading. Lake water
      quality is therefore not improved as expected. In particular summer
      concentrations rise and P retention may be negative during most of the summer.
      The P release originates from a pool accumulated in the sediment when the
      external loading was high. In most lake sediments, P bound to redox-sensitive
      iron compounds or P fixed in more or less labile organic forms constitute major
      fractions--forms that are potentially mobile and eventually may be released to
      the lake water. The duration of the recovery period following P loading reduction
      depends on the loading history, but it may last for decades in lakes with a high
      sediment P accumulation. During the phase of recovery, both the duration and net
      P release rates from the sediment seem to decline progressively. Internal P
      loading is highly influenced by the biological structure as illustrated by lakes
      shifting from the turbid to the clearwater state as a result of, for example,
      biomanipulation. In these lakes P concentrations may be reduced to 50% of the pre
      biomanipulation level and the period with negative retention during summer can
      thus be reduced considerably. The duration of internal loading can be reduced
      significantly by different restoration methods such as dredging to remove
      accumulated P or addition of iron or alum to elevate the sorption capacity of
      sediments. However, an important prerequisite for achieving long-term benefits to
      water quality is a sufficient reduction of the external P loading.

PMID- 12806080
TI  - Thyroid ultrasonography consistently identifies goiter in adults over the age of
      30 years despite a diminished response with aging of the thyroid gland to the
      effects of goitrogenesis.
AB  - Iodine deficiency is a national health problem in India and we have recently
      reported on the severity of IDD in adults and children in Gujarat province. The
      aim of this study was to determine the utility of thyroid ultrasonography to
      detect goiter in adults from an iodine-deficient population of Gujarat. We
      studied 472 adults selected by random household surveys. Data were collected on
      height, body weight, mid-upper arm circumference, thigh circumference, triceps
      skinfold thickness, thyroid size (palpation and ultrasonography), and diet.
      Casual urine samples for iodine (UI) and blood spots for TSH estimation were
      obtained. Endemic goiter is a major public health problem in Gujarat State, India
      and is probably caused by multiple factors including iodine deficiency,
      malnutrition, and other dietary goitrogens. These results indicate that thyroid
      US consistently detects goiter in adults despite a diminished thyroidal response
      to variable goitrogenic stimuli.

PMID- 12806081
TI  - Alternative attractors of shallow lakes.
AB  - Ponds and shallow lakes can be very clear with abundant submerged plants, or very
      turbid due to a high concentration of phytoplankton and suspended sediment
      particles. These strongly contrasting ecosystem states have been found to
      represent alternative attractors with distinct stabilizing feedback mechanisms.
      In the turbid state, the development of submerged vegetation is prevented by low
      underwater light levels. The unprotected sediment frequently is resuspended by
      wave action and by fish searching for food causing a further decrease of
      transparency. Since there are no plants that could serve as refuges, zooplankton
      is grazed down by fish to densities insufficient to control algal blooms. In
      contrast, the clear state in eutrophic shallow lakes is dominated by aquatic
      macrophytes. The submerged macrophytes prevent sediment resuspension, take up
      nutrients from the water, and provide a refuge for zooplankton against fish
      predation. These processes buffer the impacts of increased nutrient loads until
      they become too high. Consequently, the response of shallow lakes to
      eutrophication tends to be catastrophic rather than smooth, and various lakes
      switch back and forth abruptly between a clear and a turbid state repeatedly
      without obvious external forcing. Importantly, a switch from a turbid to a stable
      clear state often can be invoked by means of biomanipulation in the form of a
      temporary reduction of the fish stock.

PMID- 12806083
TI  - First international conference on lysophospholipids and related bioactive lipids
      in biology and disease sponsored by the Federation of American Societies of
      Experimental Biology.

PMID- 12806082
TI  - Helicobacter pylori infection in persons with intellectual disability in
      residential care in Israel.
AB  - Helicobacter pylori (formerly Campylobacter pylori ) was identified in 1982 by
      researchers from Australia as a pathogenic factor in peptic ulcer disease. Due to
      the few studies on H. pylori infection conducted in the population of persons
      with intellectual disability it was decided to conduct a clinical study in
      Israel. The purpose of the study was to determine the occurrence of H. pylori
      infection in persons who presented with severe dyspeptic symptoms and to monitor
      clinically the effect of treatment. The Division for Mental Retardation in Israel
      provides service to 6,022 persons in 53 residential care centers and 1 in central
      Israel was selected for this pilot study. The study has been performed since 1999
      and each patient who came to the medical clinic of the institution with severe
      dyspeptic symptoms was examined clinically and a blood specimen drawn for IgG
      antibodies to H. pylori (ELISA, Pharmatop Millenia). In case of positive
      serology, triple drug treatment (amoxycillin, metronidazole, and pantoprazole or
      omeprazole) was initiated for 1 week. Since 1999 a total of 43 persons (total
      population in care was 224) had severe dyspeptic symptoms and 42 persons (98%, 26
      males, 16 females, mean age 45 years, mean institutionalization 20 years) had
      Helicobacter infection. All patients were treated for 1 week, but six patients
      received an extra month of omeprazole due to persistent symptoms. At follow-up,
      clinically all patients had improvement and only seven still had minor complaints
      (83% treatment success). Persons with developmental disability, intellectual
      disability, or mental retardation in residential care presenting with severe
      dyspeptic symptoms had a high incidence of H. pylori infection. Therefore, we
      recommend serology or urea breath investigations in this population presenting
      with dyspeptic symptoms and triple drug treatment for 1 week in case of positive
      findings.

PMID- 12806084
TI  - Capping the cost of compliance with the Kyoto Protocol and recycling revenues
      into land-use projects.
AB  - There is the concern among some countries that compliance costs with commitments
      under the Kyoto Protocol may be unacceptably high. There is also the concern that
      technical difficulties with the inclusion of land use, land-use change, and
      forestry activities in non-Annex I countries might lead to an effective exclusion
      of such activities from consideration under the Protocol. This paper is proposing
      a mechanism that addresses both these concerns. In essence, it is suggested that
      parties should be able to purchase fixed-price offset certificates if they feel
      they cannot achieve compliance through other means alone, such as by improved
      energy efficiency, increased use of renewable energy, or use of the flexible
      mechanisms in the Kyoto Protocol. These offset certificates would act as a price
      cap for the cost of compliance for any party to the Protocol. Revenues from
      purchase of the offset certificates would be directed to forest-based activities
      in non-Annex I countries such as forest protection that may carry multiple
      benefits including enhancing net carbon sequestration.

PMID- 12806090
TI  - Igf2/H19 imprinting control region (ICR): an insulator or a position-dependent
      silencer?
AB  - The imprinting control region (ICR) located far upstream of the H19 gene, in
      conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in
      an allele-specific manner. On paternal inheritance, the methylated ICR silences
      the H19 gene and indirectly facilitates transcription from the distant Igf2
      promoter, whereas on the maternal chromosome the unmethylated ICR, together with
      enhancers, activates transcription of the H19 gene and thereby contributes to the
      repression of Igf2. This repression of maternal Igf2 has recently been postulated
      to be due to a chromatin boundary or insulator function of the unmethylated ICR.
      Central to the insulator model is the site-specific binding of a ubiquitous
      nuclear factor CTCF which exhibits remarkable flexibility in functioning as
      transcriptional activator or silencer. We suggest that the ICR positioned close
      to the enhancers in an episomal context might function as a transcriptional
      silencer by virtue of interaction of CTCF with its modifiers such as SIN3A and
      histone deacetylases. Furthermore, a localised folded chromatin structure
      resulting from juxtaposition of two disparate regulatory sequences (enhancer ICR)
      could be the mechanistic basis of ICR-mediated position-dependent (ICR-promoter)
      transcriptional repression in transgenic Drosophila.

PMID- 12806091
TI  - Back from the tip of the nose.

PMID- 12806092
TI  - Postimplantation whole embryo culture assay for hamsters: an alternative to rat
      and mouse.
AB  - Postimplantation whole embryo culture (WEC) assay for rats and mice has been well
      established and introduced to many laboratories. Recently WEC technique for
      rabbits has been developed; however, information on culture of other species is
      very limited. Knowing the usefulness of hamsters in classical embryotoxicology,
      we reasoned that hamster WEC could be an alternative model for the most
      frequently used rat and mouse WEC. Previously we have optimized culture
      conditions for postimplantation hamster embryos. The aim of this study was to
      test the susceptibility of hamster embryos cultured in vitro to embryotoxic
      compounds and to compare our results with those reported by others on rat or
      mouse embryo culture. For that purpose we choose three known embryotoxic
      compounds--valproic acid, cadmium chloride, and diethylstilbestrol--and tested
      them using a postimplantation hamster whole embryo culture assay. Hamster embryos
      were cultured from 7.5 days gestation for 24 h in a medium consisting of 35%
      hamster serum and 65% synthetic culture medium (Iscove's or McCoy 5A). At the end
      of the culture period, the embryos were examined morphologically, measured with
      the aid of a computer image analysis system, and total protein content was
      assessed. All three compounds exhibited dose-related embryotoxic and teratogenic
      effects in hamster embryos. The malformations observed were similar to those
      reported on rat and mouse embryos. Comparison of the results with data reported
      by other authors indicates that hamster embryos cultured in vitro might be more
      susceptible to embryotoxic stimuli than rat and mouse embryos.

PMID- 12806094
TI  - Scientists turn to journals in English.
AB  - Biomedical publications listed in Medline were analyzed based on publisher's
      location and first author's country of origin. In the present analysis I wished
      to determine the languages of biomedical publications and the publishers'
      locations.

PMID- 12806095
TI  - Policy considerations for using forests to mitigate carbon dioxide emissions.
AB  - A recent article in Nature, "Soil Fertility Limits Carbon Sequestration by Forest
      Ecosystems in a CO2-Enriched Atmosphere" by Oren and colleagues, has been widely
      reported on, and often misinterpreted, by the press. The article dampens
      enthusiasm for accelerated forest growth due to CO2 fertilization and puts in
      question the fringe theory that the world"s forests can provide an automatic
      mitigation feedback. We agree that these results increase our understanding of
      the global carbon cycle. At the same time, their relevance in the context of the
      international climate change negotiations is much more complicated than portrayed
      by newspapers such as the New York Times ("Role of Trees in Curbing Greenhouse
      Gases is Challenged", May 24, 2001) and the Christian Science Monitor ("Trees No
      Savior for Global Warming", May 25, 2001).

PMID- 12806096
TI  - Sustainable development of the cement industry and blended cements to meet
      ecological challenges.
AB  - The world production of cement has greatly increased in the past 10 years. This
      trend is the most significant factor affecting technological development and the
      updating of manufacturing facilities in the cement industry. Existing technology
      for the production of cement clinker is ecologically damaging; it consumes much
      energy and natural resources and also emits pollutants. A new approach to the
      production of blended or high-volume mineral additive (HVMA) cement helps to
      improve its ecological compatibility. HVMA cement technology is based on the
      intergrinding of portland cement clinker, gypsum, mineral additives, and a
      special complex admixture. This new method increases the compressive strength of
      ordinary cement, improves durability of the cement-based materials, and--at the
      same time--uses inexpensive natural mineral additives or industrial by-products.
      This improvement leads to a reduction of energy consumption per unit of the
      cement produced. Higher strength, better durability, reduction of pollution at
      the clinker production stage, and decrease of landfill area occupied by
      industrial by-products, all provide ecological advantages for HVMA cement.

PMID- 12806097
TI  - Carcinogenesis and chemotherapy viewed from the perspective of stoichiometric
      network analysis (SNA): what can the biological system of the elements contribute
      to an understanding of tumour induction by elemental chemical noxae (e.g., Ni2+ ,
      Cd2+ ) and to an understanding of chemotherapy?
AB  - The biological application of stoichiometric network analysis (SNA) permits an
      understanding of tumour induction, carcinogenesis, and chemotherapy. Starting
      from the Biological System of the Elements, which provides a comprehensive
      treatment of the functions and distributions of chemical (trace) elements in
      biology, an attempt is made to interrelate the essential feature of biology and-
      regrettably--of tumour genesis by superimposing SNA reasoning on common features
      of all crucial biological processes. For this purpose, aspects, effects and
      drawbacks of autocatalysis (identical reproduction which can occur either under
      control or without control [in tumours]) are linked with the known facts about
      element distributions in living beings and about interference of metals with
      tumours (in terms of both chemotherapy and carcinogenesis). The essential role of
      autocatalysis in biology and the drawbacks of either controlled or spontaneous
      cell division can be used to understand crucial aspects of carcinogenesis and
      chemotherapy because SNA describes and predicts effects of autocatalysis,
      including phase effects that may be due to some kind of intervention. The SNA
      based classifications of autocatalytic networks in cell biology are outlined here
      to identify new approaches to chemotherapy.

PMID- 12806098
TI  - Molluscan shell matrix characterization by preparative SDS-PAGE.
AB  - The glycoproteinaceous constituents of molluscan shell matrices usually resist
      chromatographical fractionation. We describe a protocol that overcomes this
      difficulty and permits collection of a large amount of shell proteins for further
      in vitro characterization. After dissolution of the mineral phase, the
      glycoproteins are fractionated "blind" on a preparative electrophoresis. They are
      subsequently detected with a polyclonal antibody raised against the whole matrix.

PMID- 12806099
TI  - Synthesis of platinum complexes from N-benzyl-2-aminoethanethiol derivatives.
AB  - Twelve new platinum(II) complexes, analogs of cisplatin, containing a 2
      aminoethanethiol N-substituted by several benzyl groups have been prepared and
      characterized in good yields. The ligands were obtained by reaction between 2
      aminoethanethiol hydrochloride and different benzyl halides

PMID- 12806100
TI  - Down from the ivory tower: climate science faces the real world.

PMID- 12806101
TI  - Global warming: the balance of evidence and its policy implications. A review of
      the current state-of-the-controversy.
AB  - Global warming and attendant climate change have been controversial for at least
      a decade. This is largely because of its societal implications. With the recent
      publication of the Third Assessment Report of the United Nations'
      Intergovernmental Panel on Climate Change there has been renewed interest and
      controversy about how certain the scientific community is of its conclusions:
      that humans are influencing the climate and that global temperatures will
      continue to rise rapidly in this century. This review attempts to update what is
      known and in particular what advances have been made in the past 5 years or so.
      It does not attempt to be comprehensive. Rather it focuses on the most
      controversial issues, which are actually few in number. They are: Is the surface
      temperature record accurate or is it biased by heat from cities, etc.?, Is that
      record significantly different from past warmings such as the Medieval Warming
      Period?, Is not the sun's increasing activity the cause of most of the warming?,
      Can we model climate and predict its future, or is it just too complex and
      chaotic?, Are there any other changes in climate other than warming, and can they
      be attributed to the warming? Despite continued uncertainties, the review finds
      affirmative answers to these questions. Of particular interest are advances that
      seem to explain why satellites do not see as much warming as surface instruments,
      how we are getting a good idea of recent paleoclimates, and why the 20th century
      temperature record was so complex. It makes the point that in each area new
      information could come to light that would change our thinking on the
      quantitative magnitude and timing of anthropogenic warming, but it is unlikely to
      alter the basic conclusions. Finally, there is a very brief discussion of the
      societal policy response to the scientific message, and the author comments on
      his 2-year email discussions with many of the world's most outspoken critics of
      the anthropogenic warming hypothesis.

PMID- 12806102
TI  - Validation of two global and generic quality of life questionnaires for
      population screening: SCREENQOL and SEQOL.
AB  - Population screening may harm quality of life (QoL), and traditional health
      related QoL tools could be inadequate to evaluate this risk. Two global and
      generic QoL instruments were developed for studying the QoL consequences of
      screening (SCREENQOL), and QoL variation in a normal population (SEQOL).
      SCREENQOL and SEQOL (Self-Evaluation of Quality of Life Questionnaire) are self
      administered questionnaires with items rated on 5-point Likert scales. SCREENQOL
      consists of 21 items measuring QoL across 6 different dimensions based upon
      validated QoL questionnaires. SEQOL consists of 317 items measuring QoL across 8
      different dimensions, based on an integrative theory of QoL, a theoretical
      framework from a Danish QoL survey involving 7,222 persons 31 to 33 years old.
      For further validation, SEQOL and SCREENQOL were sent to 2,460 persons 18 to 88
      years old randomly selected from the Danish Central Person Register together with
      Nottingham Health Profile (NHP) and Sickness Impact Profile (SIP). For SCREENQOL
      and SEQOL, test-retest reliability correlation was both >0.8, Cronbach's alpha
      was 0.65 and 0.75, correlation (r) to NHP was 0.67 and 0.49, to SIP 0.46 and
      0.27, respectively (p < 0.05). Adjustment for health status made the correlation
      to SIP stronger among the sick (r = 0.68 and 0.41, respectively). For SCREENQOL
      and SEQOL, 61 and 111 respondents were needed to detect 3% difference in QoL.
      SCREENQOL and SEQOL are both valid as they show high levels of reliability,
      sensitivity, and consistency.

PMID- 12806103
TI  - Are there mutator polymerases?
AB  - DNA polymerases are involved in different cellular events, including genome
      replication and DNA repair. In the last few years, a large number of novel DNA
      polymerases have been discovered, and the biochemical analysis of their
      properties has revealed a long list of intriguing features. Some of these
      polymerases have a very low fidelity and have been suggested to play mutator
      roles in different processes, like translesion synthesis or somatic
      hypermutation. The current view of these processes is reviewed, and the current
      understanding of DNA polymerases and their role as mutator enzymes is discussed.

PMID- 12806104
TI  - A calorimetric characterization of Cr(VI)-reducing Arthrobacter oxydans at
      different phases of the cell growth cycle.
AB  - This is the first of a series of calorimetric studies designed to characterize
      and understand survival mechanisms of metal-reducing bacteria isolated from metal
      polluted environments. In this paper we introduce a new concept of thermal
      spectrum of the endothermic melting of complex biological systems (e.g.,
      proteins, nucleic acids, ribosomes, membrane structures) in intact cells. All
      thermal spectra measured are thermograms that describe the temperature dependence
      of heat capacity change of the complex systems of biologically active substances
      in bacterial cells. This new concept of thermal spectrum was applied to
      investigate spectral features from intact cells of Cr(VI)-reducer Arthrobacter
      oxydans at different points of their growth conditions and stages. Over the
      temperature range of 40-105 degrees C, we observed that spectral changes are
      particularly significant in the 40-90 degrees C interval. This may correspond to
      the orderly changes in subcellular structural elements: proteins, ribosomes and
      RNA, membranes, and various structural elements of the cell wall during different
      points of the growth cycle and growth conditions. Spectral changes in the 90-105
      degrees C region are less pronounced, implicating that the structural composition
      of DNA-Protein (DNP) complexes may change little.

PMID- 12806105
TI  - Treatment of bulbar urethral strictures a review, with personal critical remarks.
AB  - This is a review article on treatment of bulbar urethral strictures with personal
      critical remarks on newer developments. As a treatment of first intention there
      exists 4 options : dilatation, urethrotomy, end to end anastomosis and free
      graft, open urethroplasty. Success rate of dilatation and visual urethrotomy
      after 4 years is only 20 en 40% respectively. Laser urethrotomy could not fulfill
      expectations. End to end anastomosis obtains a very high success rate but is only
      applicable for short strictures. Free graft urethroplasty obtains success rates
      of +/- 80%. There is considerable debate on the best material for grafting.
      Buccal mucosa graft is the new wave, but this is not based on scientific data.
      Whether this graft should be used dorsally or ventrally is also a point of
      discussion. In view of the good results published with both techniques it is
      probably of no importance. Intraluminal stents are not indicated for complicated
      cases and give only good results in those cases which can easily be treated with
      other techniques. Metal self-retaining urethral stent, resorbable stents and
      endoscopic urethroplasty is briefly discussed. Redo's and complicated urethral
      strictures need often other solutions. Here skin flap from the penile skin and
      scrotal flap can be used. Advantages and drawbracks of both are discussed. There
      is still a place for two-stage procedures in complicated redo"s. The two-stage
      mesh-graft urethroplasty offers advantage over the use of scrotal skin. Some
      other rare techniques like substitution with bowel and pudendal thigh flap, to
      cover deep defects, are also discussed.

PMID- 12806106
TI  - Migration and enrichment of arsenic in the rock-soil-crop plant system in areas
      covered with black shale, Korea.
AB  - The Okchon black shale, which is part of the Guryongsan Formation or the Changri
      Formation of Cambro-Ordovician age in Korea provides a typical example of natural
      geological materials enriched with potentially toxic elements such as U, V, Mo,
      As, Se, Cd, and Zn. In this study, the Dukpyung and the Chubu areas were selected
      to investigate the migration and enrichment of As and other toxic elements in
      soils and crop plants in areas covered with black shale. Rock and soil samples
      digested in 4-acid solution (HCl+HNO3+HF+HClO4) were analyzed for As and other
      heavy metals by ICP-AES and ICP-MS, and plant samples by INAA. Mean concentration
      of As in Okchon black shale is higher than those of both world average values of
      shale and black shale. Especially high concentration of 23.2 mg As kg(-1) is
      found in black shale from the Dukpyung area. Mean concentration of As is highly
      elevated in agricultural soils from the Dukpyung (28.2 mg kg(-1)) and the Chubu
      areas (32.6 mg kg(-1)). As is highly elevated in rice leaves from the Dukpyung
      (1.14 mg kg(-1)) and the Chubu areas (1.35 mg kg(-1)). The biological absorption
      coefficient (BAC) of As in plant species decreases in the order of rice leaves >
      corn leaves > red pepper = soybean leaves = sesame leaves > corn stalks > corn
      grains. This indicates that leafy plants tend to accumulate As from soil to a
      greater degree than cereal products such as grains.

PMID- 12806107
TI  - Atmospheric chemistry and air pollution.
AB  - Atmospheric chemistry is an important discipline for understanding air pollution
      and its impacts. This mini-review gives a brief history of air pollution and
      presents an overview of some of the basic photochemistry involved in the
      production of ozone and other oxidants in the atmosphere. Urban air quality
      issues are reviewed with a specific focus on ozone and other oxidants, primary
      and secondary aerosols, alternative fuels, and the potential for chlorine
      releases to amplify oxidant chemistry in industrial areas. Regional air pollution
      issues such as acid rain, long-range transport of aerosols and visibility loss,
      and the connections of aerosols to ozone and peroxyacetyl nitrate chemistry are
      examined. Finally, the potential impacts of air pollutants on the global-scale
      radiative balances of gases and aerosols are discussed briefly.

PMID- 12806110
TI  - Making headway: the roles of Hox genes and neural crest cells in craniofacial
      development.
AB  - Craniofacial development is an extraordinarily complex process requiring the
      orchestrated integration of multiple specialized tissues such as the surface
      ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate
      the central and peripheral nervous systems, axial skeleton, musculature, and
      connective tissues of the head and face. How do the characteristic facial
      structures develop in the appropriate locations with their correct shapes and
      sizes, given the widely divergent patterns of cell movements that occur during
      head development? The patterning information could depend upon localized
      interactions between the epithelial and mesenchymal tissues or alternatively, the
      developmental program for the characteristic facial structures could be intrinsic
      to each individual tissue precursor. Understanding the mechanisms that control
      vertebrate head development is an important issue since craniofacial anomalies
      constitute nearly one third of all human congenital defects. This review
      discusses recent advances in our understanding of neural crest cell patterning
      and the dynamic nature of the tissue interactions that are required for normal
      craniofacial development.

PMID- 12806111
TI  - The use of spreadsheets for pharmacokinetic simulations.
AB  - The use of simple spreadsheets is described to create simulations of complex
      pharmacokinetic phenomena. The basics of spreadsheets are first described and are
      developed to demonstrate classical pharmacokinetics without the use of
      differential or integral calculus. Using standard spreadsheet commands, the
      technique is shown to be applicable to the full range of advanced pharmacokinetic
      simulations. Demonstrations of the effect of a variety of physiological
      eventualities are included to show the versatility of the technique. The
      technique is very simple to use and is always in the complete control of the
      modeller.

PMID- 12806113
TI  - Neurophysiological effects of chronic indoor environmental toxic mold exposure on
      children.
AB  - The phenomenon of building-related diseases is attracting much research interest
      in recent years because of the extent to which it affects people with compromised
      immune systems, especially children. In this study, we reported the neurological
      findings in children who attended our Center because of chronic exposure to toxic
      molds. Clinical neurological and neurobehavioral questionnaires were administered
      with the cooperation of the children's parents. The children then underwent a
      series of neurophysiological tests including electroencephalogram (EEG),
      brainstem evoked potential (BAEP), visual evoked potential (VEP), and
      somatosensory evoked potential (SSEP). The results showed high levels of
      abnormalities in the analysis of the subjective responses derived from the
      questionnaires. The EEG examination was abnormal in seven out of ten of the
      patients compared to the controls with only one in ten with episodes of
      bihemispheric sharp activity. In all the patients, there was frontotemporal theta
      wave activity that seemed to indicate diffuse changes characteristic of metabolic
      encephalopathies. Also, there was highly marked 1 to 3 Hz delta activity that was
      asymmetrical in the right hemisphere of the brain in three out of ten patients.
      The waveforms of BAEP showed abnormalities in 90% of the patients with both 15'
      and 31' check sizes compared to none in the controls. There were significant
      delays in waveform V in a majority of the patients representing dysfunctional
      cognitive process and conductive hearing loss in both ears. VEP showed clear
      abnormalities in four in ten of the patients with P100 amplitudes and latencies
      decreased bilaterally. In all the patients, there was slowing of conduction in
      the right tibial at an average of 36.9 ms and there was significant decrease in
      amplitude of response at the proximal stimulation site. Sensory latencies
      obtained in the median, ulnar, and sural nerves bilaterally showed abnormalities
      in five out of ten compared to none in the controls. The median, ulnar, and sural
      sensory potentials were abnormal in six out of ten patients. There was
      prolongation of the median distal sensory latencies bilaterally at an average of
      4.55 ms on the right and an average of 6.10 ms on the left as compared to the
      ulnars of 2.55 ms bilaterally. There was no abnormality in the controls. These
      findings represent evidence of diffuse polyneuropathy to which three patients
      demonstrated borderline slow motor conduction at an average of 41.1 ms. Overall,
      the objective neurophysiological measurements (EEG, BAEP, VEP, and SSEP) were
      abnormal, indicating significant neurological deficits in all the patients. Our
      findings revealed the extent to which toxic molds can affect the neurological and
      behavioral status of children. Further work should be encouraged in this regard.

PMID- 12806114
TI  - Creative problem solving and social cooperation of effective physical therapy
      practice: a pioneer study and overview.
AB  - Action research (AR) has an important role to play in educating physical
      therapists. Increasing efforts should be encouraged to instigate AR programs in
      physical therapy practice and clinical education. Such programs commonly require
      considerable effort and understanding by clinical instructors, and require
      adoption of new educational methods. AR programs can lead physical therapists and
      clinicians to be more questioning and reflective in evaluating practical
      questions regarding patient therapy and education. The purpose of this article is
      to educate the readers on the importance of AR and to provide a few relevant
      references on that topic. A specific study is described in this paper in which
      physical therapy clinical instructors participated in a structured workshop
      designed to demonstrate the values of AR and how such values can be incorporated
      in teaching their students. AR can lead to improved therapist-patient interaction
      and help solve specific practical problems arising during therapy sessions.

PMID- 12806115
TI  - Elderly persons with intellectual disability: a study of clinical
      characteristics, functional status, and sensory capacity.
AB  - Longer life expectancy is resulting in increasing numbers of elderly adults with
      intellectual disability (ID). There has been the question whether persons with ID
      demonstrate early signs of aging before the general population. The aim of this
      study was to determine if persons with ID (with and without Down syndrome) showed
      premature aging changes compared with a control group. Elderly persons (n = 24,
      average age of 61) from one residential care center in Israel and younger adults
      from another center (n = 37, average age of 45) were compared with elderly
      residents without ID in an independent living facility. The study considered
      demographic data, medical data, anthropometric measurements, body fat and body
      mass index, flexibility, and sensorimotor function tests. The results showed that
      the persons with ID had basically similar body composition to that of persons
      without ID, however, the functional performance of elderly adults with ID was
      more impaired. We postulate that the slower functioning responses may be
      explained by a less physically active lifestyle, that may accelerate the onset of
      disease and result in symptoms associated with aging that are detrimental to
      health. It is therefore important that persons with ID participate in physical
      activity and exercises in order to promote health and prevent disease.

PMID- 12806116
TI  - Cell cycle dynamics of the nuclear envelope.
AB  - The nuclear envelope (NE) consists of an inner and an outer membrane, nuclear
      pore complexes, and the underlying nuclear lamina, a filamentous scaffold
      structure formed by lamins. The inner membrane is linked to the lamina and
      chromatin by its integral membrane proteins, such as lamin B receptor (LBR),
      emerin, and various isoforms of lamina-associated polypeptides (LAP) 1 and 2,
      which bind lamins and/or chromatin. During mitosis, the NE is disassembled upon
      phosphorylation of its core components, and the NE is torn apart by a dynein
      driven microtubule-dependent mechanism. Nuclear reassembly after sister chromatid
      separation requires a timely coordinated and dephosphorylation-dependent
      association of lamin-binding proteins and lamins with chromosomal proteins and
      targeting of membranes to specific sites on chromosomes. Various chromatin
      binding domains in lamina proteins, such as the LEM domain, present in all LAP2
      isoforms and in emerin, as well as unique regions in lamina proteins and in
      specific LAP2 isoforms have been implicated in defined steps of NE reformation.
      Furthermore, novel mechanisms of membrane fusion involving Ran GTPase are just
      beginning to emerge.

PMID- 12806117
TI  - The DNA polymerase alpha-primase complex: multiple functions and interactions.
AB  - DNA polymerase alpha (pol alpha) holds a special position among the growing
      family of eukaryotic DNA polymerases. In fact, pol alpha is associated with DNA
      primase to form a four subunit complex and, as a consequence, is the only enzyme
      able to start DNA synthesis de novo. Because of this peculiarity the major role
      of the DNA polymerase alpha-primase complex (pol-prim) is in the initiation of
      DNA replication at chromosomal origins and in the discontinuous synthesis of
      Okazaki fragments on the lagging strand of the replication fork. However, pol
      prim seems to play additional roles in other complex cellular processes, such as
      the response to DNA damage, telomere maintenance, and the epigenetic control of
      higher order chromatin assembly.

PMID- 12806118
TI  - DNA polymerase gamma in mitochondrial DNA replication and repair.
AB  - Mutations in mitochondrial DNA (mtDNA) are associated with aging, and they can
      cause tissue degeneration and neuromuscular pathologies known as mitochondrial
      diseases. Because DNA polymerase gamma (pol gamma) is the enzyme responsible for
      replication and repair of mitochondrial DNA, the burden of faithful duplication
      of mitochondrial DNA, both in preventing spontaneous errors and in DNA repair
      synthesis, falls on pol gamma. Investigating the biological functions of pol
      gamma and its inhibitors aids our understanding of the sources of mtDNA
      mutations. In animal cells, pol gamma is composed of two subunits, a larger
      catalytic subunit of 125-140 kDa and second subunit of 35-55 kDa. The catalytic
      subunit contains DNA polymerase activity, 3'-5' exonuclease activity, and a 5'
      dRP lyase activity. The accessory subunit is required for highly processive DNA
      synthesis and increases the affinity of pol gamma to the DNA.

PMID- 12806119
TI  - Is there a seasonal difference in the detection of Trichomonas vaginalis by
      cervical cytology?
AB  - This objective of our study was to determine the prevalence of a Trichomonas
      vaginalis diagnosis in routine Papanicolaou smears and whether it is seasonal. We
      reviewed the diagnosis rendered for 93,681 Papanicolaou smears evaluated at a
      medical school hospital laboratory between 1992 and 1997. The occurrence of a
      diagnosis of T. vaginalis was analyzed by year, by quarter, and by month using a
      generalized linear regression model. The prevalence of a T. vaginalis diagnosis
      during the 6-year study period was 3.1%. The between-month and between-quarter
      comparisons of prevalence were not statistically different. In the population
      reported here, the prevalence of a Papanicolaou smear diagnosis of T. vaginalis
      was low and no seasonal difference in making this diagnosis was identified.

PMID- 12806120
TI  - Apoptosis gene hunting using retroviral expression cloning: identification of
      vacuolar ATPase subunit E.
AB  - Over the past 10-15 years there has been an explosion of interest in apoptosis.
      The delayed realisation that cell death is an essential part of life for any
      multicellular organism has meant that, despite the recent and rapid developments
      of the last decade, the precise biochemical pathways involved in apoptosis remain
      incomplete and potentially novel genes may, as yet, remain undiscovered. The hunt
      is therefore on to bridge the remaining gaps in our knowledge. Our contribution
      to this research effort utilises a functional cloning approach to isolate
      important regulatory genes involved in apoptosis. This mini-review focuses on the
      use and advantages of a retroviral expression cloning strategy and describes the
      isolation and identification of one such potential apoptosis regulatory gene,
      namely that encoding vacuolar ATPase subunit E.

PMID- 12806121
TI  - AFM imaging of lipid domains in model membranes.
AB  - Characterization of the two-dimensional organization of biological membranes is
      one of the most important issues that remains to be achieved in order to
      understand their structure-function relationships. According to the current view,
      biological membranes would be organized in in-plane functional microdomains. At
      least for one category of them, called rafts, the lateral segregation would be
      driven by lipid-lipid interactions. Basic questions like the size, the kinetics
      of formation, or the transbilayer organization of lipid microdomains are still a
      matter of debate, even in model membranes. Because of its capacity to image
      structures with a resolution that extends from the molecular to the microscopic
      level, atomic force microscopy (AFM) is a useful tool for probing the mesoscopic
      lateral organization of lipid mixtures. This paper reviews AFM studies on lateral
      lipid domains induced by lipid-lipid interactions in model membranes.

PMID- 12806122
TI  - Inhibition of return biases orienting during the search of complex scenes.
AB  - In Klein and MacInnes, observers searched a complex scene for a camouflaged
      target. Reflecting Inhibition of Return (IOR) observers were slower to detect and
      saccade to uncamouflaged probes that interrupted active search when these were
      placed in the vicinity of a recent fixation. To explore the generality of this
      finding of IOR during search, we changed the mental state of the observer at the
      time of the probes by instructing observers to inspect the scene until they found
      something interesting and stop there. After this voluntary cessation of search,
      we presented an uncamouflaged probe that observers were required to foveate.
      Extending our previous demonstration, we observed a relative increase in the time
      required to locate these probes when they were in the general region of a
      previous fixation so long as the scene was maintained. When the scene was
      removed, probe reaction time was unaffected by distance from the last fixation.
      The pattern of results supports the proposal that IOR biases overt orienting
      during search.

PMID- 12806123
TI  - DNA polymerase epsilon - more than a polymerase.
AB  - This paper presents a comprehensive review of the structure and function of DNA
      polymerase epsilon. Together with DNA polymerases alpha and delta, this enzyme
      replicates the nuclear DNA in the eukaryotic cell. During this process, DNA
      polymerase alpha lays down RNA-DNA primers that are utilized by DNA polymerases
      delta and epsilon for the bulk DNA synthesis. Attempts have been made to assign
      these two enzymes specifically to the synthesis of the leading and the lagging
      strand. Alternatively, the two DNA polymerases may be needed to replicate
      distinct regions depending on chromatin structure. Surprisingly, the essential
      function of DNA polymerase epsilon does not depend on its catalytic activity, but
      resides in the nonenzymatic carboxy-terminal domain. This domain not only
      mediates the interaction of the catalytic subunit with the three smaller
      regulatory subunits, but also links the replication machinery to the S phase
      checkpoint. In addition to its role in DNA replication, DNA polymerase epsilon
      fulfils roles in the DNA synthesis step of nucleotide excision and base excision
      repair, and has been implicated in recombinational processes in the cell.

PMID- 12806124
TI  - Rheology of biopolymer solutions and gels.
AB  - Rheological techniques and methods have been employed for many decades in the
      characterization of polymers. Originally developed and used on synthetic
      polymers, rheology has then found much interest in the field of natural (bio)
      polymers. This review concentrates on introducing the fundamentals of rheology
      and on discussing the rheological aspects and properties of the two major classes
      of biopolymers: polysaccharides and proteins. An overview of both their solution
      properties (dilute to semi-dilute) and gel properties is described.

PMID- 12806125
TI  - Effect of putting grip on eye and head movements during the golf putting stroke.
AB  - The objective of this article is to determine the effect of three different
      putting grips (conventional, cross-hand, and one-handed) on variations in eye and
      head movements during the putting stroke. Seven volunteer novice players, ranging
      in age from 21 to 22 years, participated in the study. During each experimental
      session, the subject stood on a specially designed platform covered with
      artificial turf and putted golf balls towards a standard golf hole. The three
      different types of grips were tested at two distances: 3 and 9 ft. For each
      condition, 20 putts were attempted. For each putt, data were recorded over a 3-s
      interval at a sampling rate of 100 Hz. Eye movements were recorded using a helmet
      mounted eye movement monitor. Head rotation about an imaginary axis through the
      top of the head and its center-of-rotation was measured by means of a
      potentiometer mounted on a fixed frame and coupled to the helmet. Putter-head
      motion was measured using a linear array of infrared phototransistors embedded in
      the platform. The standard deviation (STD, relative to the initial level) was
      calculated for eye and head movements over the duration of the putt (i.e., from
      the beginning of the backstroke, through the forward stroke, to impact). The
      averaged STD for the attempted putts was calculated for each subject. Then, the
      averaged STDs and other data for the seven subjects were statistically compared
      across the three grip conditions. The STD of eye movements were greater (p < 0.1)
      for conventional than cross-hand (9 ft) and one-handed (3 and 9 ft) grips. Also,
      the STD of head movements were greater (p < 0.1; 3 ft) for conventional than
      cross-hand and one-handed grips. Vestibulo-ocular responses associated with head
      rotations could be observed in many 9 ft and some 3 ft putts. The duration of the
      putt was significantly longer (p < 0.05; 3 and 9 ft) for the one-handed than
      conventional and cross-hand grips. Finally, performance, or percentage putts
      made, was significantly better (p < 0.05; 9 ft) for cross-hand than conventional
      grip. The smaller variations, both in eye movements during longer putts and head
      movements during shorter putts, using cross-hand and one-handed grips may explain
      why some golfers, based on their playing experience, prefer these over the
      conventional grip. Also, the longer duration for the one-handed grip, which
      improves tempo, may explain why some senior players prefer the long-shaft
      (effectively one-handed grip) putter.

PMID- 12806126
TI  - Chemical stabilisation of collagen as a biomimetic.
AB  - Collagen is the most abundant protein in animals and because of its high
      mechanical strength and good resistance to degradation has been utilized in a
      wide range of products in industry whilst its low antigenicity has resulted in
      its widespread use in medicine. Collagen products can be purified from fibres,
      molecules reconstituted as fibres or from specific recombinant polypeptides with
      preferred properties. A common feature of all these biomaterials is the need for
      stable chemical cross-linking to control the mechanical properties and the
      residence time in the body, and to some extent the immunogenicity of the device.
      This can be achieved by a number of different cross-linking agents that react
      with specific amino acid residues on the collagen molecule imparting individual
      biochemical, thermal and mechanical characteristics to the biomaterial. In this
      review we have summarised the major techniques for testing these characteristics
      and the mechanisms involved in the variety of cross-linking reactions to achieve
      particular properties.

PMID- 12806127
TI  - Dermoid cyst of the floor of the mouth.
AB  - Dermoid cysts of the floor of the mouth are rare lesions thought to be caused by
      entrapment of germinal epithelium during the closure of the mandibular and hyoid
      branchial arches. They usually present as a nonpainful swelling. This type of
      lesion occurs more frequently in patients between 15 and 35 years, but can be
      seen in all age ranges. Histologically, all dermoids are lined by epidermis. The
      contents of the cyst lining determine the histological categories of the cyst:
      epidermoid, if epidermis is lining the cyst; dermoid, if skin annexes exist; or
      teratoid, if there are tissues derivated from the three germinal layers.
      Anatomical classification is useful for surgical approach choice, intra- or
      extraorally. This report presents a case of a dermoid cyst of the floor of the
      mouth in a 12-year-old patient, and a review of all steps necessary for its
      diagnosis and treatment was made.

PMID- 12806128
TI  - Amylin in the periphery.
AB  - Amylin (islet amyloid polypeptide) is a peptide synthesized principally in the
      beta-cells of the pancreatic islets together with insulin and has actions as a
      hormone, growth factor, and modifier of behavior. As a hormone, amylin acts to
      modify gastric motility, renal resorption, and has metabolic actions. It is
      postulated that the principal function of amylin as a hormone is the activation
      of physiological processes associated with feeding. As a growth factor, amylin
      acts on bone cells, renal proximal tubular cells, and islet beta-cells. Amylin
      has important targets in the brain that mediate its actions in the modification
      of behavior, including thirst and satiety. In man, amylin can form islet amyloid
      deposits, an event linked to the reduction of b-cell mass and loss of signal
      secretion coupling. Recent evidence has defined a new role for monomeric amylin
      as a growth factor and regulator of beta-cell mass that is postulated to be a key
      factor in pathophysiological processes that result in overt diabetes.

PMID- 12806129
TI  - Thermodynamic molecular switch in sequence-specific hydrophobic interaction: two
      computational models compared.
AB  - We have shown in our published work the existence of a thermodynamic switch in
      biological systems wherein a change of sign in DeltaCp(o)(T)reaction leads to a
      true negative minimum in the Gibbs free energy change of reaction, and hence, a
      maximum in the related K(eq). We have examined 35 pair-wise, sequence-specific
      hydrophobic interactions over the temperature range of 273-333 K, based on data
      reported by Nemethy and Scheraga in 1962. A closer look at a single example, the
      pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the
      significant differences when the data are analyzed using the Nemethy-Scheraga
      model or treated by the Planck-Benzinger methodology which we have developed. The
      change in inherent chemical bond energy at 0 K, DeltaH(o)(T0) is 7.53 kcal mol(
      1) compared with 2.4 kcal mol(-1), while <Ts> is 365 K as compared with 355 K,
      for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At <Tm>, the
      thermal agitation energy is about five times greater than DeltaH(o)(T0) in the
      Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga
      model. The results imply that the negative Gibbs free energy minimum at a well
      defined <Ts>, where TDeltaS(o) = 0 at about 355 K, has its origin in the sequence
      specific hydrophobic interactions, which are highly dependent on details of
      molecular structure. The Nemethy-Scheraga model shows no evidence of the
      thermodynamic molecular switch that we have found to be a universal feature of
      biological interactions. The Planck-Benzinger method is the best known for
      evaluating the innate temperature-invariant enthalpy, DeltaH(o)(T0), and provides
      for better understanding of the heat of reaction for biological molecules.

PMID- 12806130
TI  - Asymmetric cell kinetics genes: the key to expansion of adult stem cells in
      culture.
AB  - A singular challenge in stem cell research today is the expansion and propagation
      of functional adult stem cells. Unlike embryonic stem cells, which are immortal
      in culture, adult stem cells are notorious for the difficulty encountered when
      attempts are made to expand them in culture. One overlooked reason for this
      difficulty may be the inherent asymmetric cell kinetics of stem cells in
      postnatal somatic tissues. Senescence is the expected fate of a culture whose
      growth depends on adult stem cells that divide with asymmetric cell kinetics.
      Therefore, the bioengineering of strategies to expand adult stem cells in culture
      requires knowledge of cellular mechanisms that control asymmetric cell kinetics.
      The properties of several genes recently implicated to function in a cellular
      pathway(s) that regulates asymmetric cell kinetics are discussed. Understanding
      the function of these genes in asymmetric cell kinetics mechanisms may be the key
      that unlocks the adult stem cell expansion problem.

PMID- 12806131
TI  - Membrane pathology in schizophrenia: implication for arachidonic acid signaling.
AB  - Schizophrenia is a major mental disorder with no clearly identified
      pathophysiology. A variety of theories has been proposed to explain the
      pathophysiology of schizophrenia. One approach that is finding empirical support
      is the investigation of membrane composition and function. Evidence to date
      suggests that there are defects in phospholipid metabolism and cell signaling in
      schizophrenia. Specifically, low levels of arachidonic acid (AA)-enriched
      phospholipids have been observed in both central and peripheral tissues. It is
      well known that changes in membrane composition are associated with a variety of
      functional consequences. Since AA has many key roles in neural functioning,
      understanding its significance for the pathophysiology of schizophrenia may lead
      to novel approaches to improving treatment of schizophrenia. The purpose of this
      review is thus to explore some of the roles of AA signaling in biological,
      physiological, and clinical phenomena observed in schizophrenia.

PMID- 12806132
TI  - The behaviour of 134Cs, 60Co, and 85Sr radionuclides in marine environmental
      sediment.
AB  - This work describes experimental investigations and modelling studies on the
      sorption of radionuclides 134Cs, 60Co, and 85Sr by certain marine sediments
      within Egypt. The chemical composition of the marine sediments was determined.
      The soluble salts were measured for the sediments and the concentrations of the
      released cations, Al3+, Fe3+, and Si4+, were measured for the sediment materials
      in 0.1 M NaClO4 aqueous solution at different hydrogen ion concentrations. The
      two main factors that control the uptake of the radionuclides onto the sediment
      are the pH and the exchangeable capacities of the sediment materials. Surface
      complex model was used to estimate the surface charge densities and the electric
      surface potential of the marine sediment materials. These two parameters were
      calculated at the surface capacity sites of the sediment materials. The
      desorption of the adsorbed cations was determined by means of selective
      consecutive extraction tests using different chemical reagents including (1) 1 M
      MgCl2 (pH 7), (2) 1 M ammonium oxalate (pH 3-5), (3) 0.04 M NH2OH,HCl in 25%
      acetic acid (pH 3-4), (4) H2O2 in 5% HNO3(pH 2-3), and (5) digestion with nitric
      acid followed by hydrofluoric and perchloric acids (pH 2).

PMID- 12806133
TI  - Calcitonin gene-related peptide in tension-type headache.
AB  - In the last 10 years there has been increasing interest in the role of calcitonin
      gene-related peptide (CGRP) in primary headaches. Tension-type headache is one of
      the most common and important types of primary headaches, and ongoing nociception
      from myofascial tissues may play an important role in the pathophysiology of this
      disorder. CGRP sensory fibers are preferentially located in the walls of
      arteries, and nerve fibers containing CGRP accompany small blood vessels in human
      cranial muscles. It is well established that nociception may lead to release of
      CGRP from sensory nerve endings and from central terminals of sensory afferents
      into the spinal cord. It has also been shown that density of CGRP fibers around
      arteries is increased in persistently inflamed muscle. These findings indicate
      that ongoing activity in sensory neurons in the cranial muscles may be reflected
      in changes of plasma levels of neuropeptides in patients with chronic tension
      type headache. To explore the possible role of CGRP in tension-type headache,
      plasma levels of CGRP were measured in patients with chronic tension-type
      headache. This study showed that plasma levels of CGRP are normal in patients and
      unrelated to headache state. However, the findings of normal plasma levels of
      CGRP do not exclude the possibility that abnormalities of this neuropeptide at
      the neuronal or peripheral (pericranial muscles) levels play a role in the
      pathophysiology of tension-type headache. Investigation of CGRP in other
      compartments with new sensitive methods of analysis is necessary to clarify its
      role in tension-type headache.

PMID- 12806134
TI  - Purification of peroxisomes in a self-generated gradient.
AB  - In iodixanol, peroxisomes are the densest organelle in the light mitochondrial
      fraction and are therefore easily separated from the other components (lysosomes,
      mitochondria, etc.) in a self-generated gradient. Self-generated gradients make
      sample handling very easy and are highly reproducible but need to be formed in
      either a vertical, near-vertical, or small volume high-performance fixed-angle
      rotor. The resolution of the peroxisomes is far superior than that in sucrose
      and, unlike in Percoll there is no contamination from endoplasmic reticulum.

PMID- 12806135
TI  - Purification of peroxisomes in a preformed iodixanol gradient in a fixed-angle
      rotor.
AB  - In iodixanol, peroxisomes are the densest organelle in the light mitochondrial
      fraction and are therefore easily separated from the other components (lysosomes,
      mitochondria, etc.) in a preformed isosmotic continuous gradient. The resolution
      of the peroxisomes is far superior than that in sucrose and, unlike in Percoll
      there is no contamination from endoplasmic reticulum.

PMID- 12806136
TI  - Separation of monocytes from whole human blood.
AB  - Human peripheral blood monocytes are isolated by flotation from whole blood
      through a single low-density barrier prepared from OptiPrep at 4 degrees C. The
      separation from lymphocytes depends on the more rapid rate of flotation of the
      monocytes because of their slightly lower density and larger size. The method
      works optimally only with fresh (within 2 h of drawing) EDTA-anticoagulated
      blood. Preliminary evidence suggests that this technique may be applicable to
      blood from rats.

PMID- 12806137
TI  - Isolation of a mouse motoneuron-enriched fraction from mouse spinal cord on a
      density barrier.
AB  - After a combined enzymic and mechanical disruption of the spinal cord tissue, the
      low-density motoneurons band at the interface of a 1.06-g/ml barrier through
      which other contaminating cells sediment.

PMID- 12806138
TI  - OptiPrep density gradient solutions for macromolecules and macromolecular
      complexes.
AB  - Any density gradient for the isolation of mammalian cells should ideally only
      expose the sedimenting particles to an increasing concentration of the gradient
      solute. Thus they will experience only an increasing density and viscosity, other
      parameters such as osmolality, pH, ionic strength and the concentration of
      important additives (such as EDTA or divalent cations) should remain as close to
      constant as possible. This Protocol Article describes the strategies for the
      dilution of OptiPrep in order to prepare such solutions for mammalian cells.

PMID- 12806139
TI  - Rapid purification of nuclei from animal and plant tissues and cultured cells.
AB  - Nuclei are isolated by buoyant density banding in a discontinuous iodixanol
      gradient, under isoosmotic conditions. The low viscosity of the gradient allows
      the purification to be carried out at 10,000g in only 20 min. The method avoids
      possible damage to nucleoprotein complexes caused by hyperosmotic sucrose
      gradients. Although developed for mammalian liver the method can be applied (with
      or without minor modifications) to any tissue or cell type.

PMID- 12806140
TI  - Separation of membrane vesicles and cytosol from cultured cells and bacteria in a
      preformed discontinuous gradient.
AB  - There are many situations when it is necessary to separate rapidly and
      efficiently a cytosolic and a membrane vesicle fraction from either cultured
      cells or from bacteria. Flotation of the vesicles through a low-density barrier
      from a dense sample zone using the low viscosity medium iodixanol allows complete
      separation of these compartments. As the sample is exposed to the gmax the
      tendency of the proteins to sediment overcomes any diffusion in the opposite
      direction.

PMID- 12806141
TI  - Low-avidity antibodies to carbonic anhydrase-I and -II in autoimmune chronic
      pancreatitis.
AB  - Antibodies (Abs) to carbonic anhydrase (isoforms CA-I and CA-II) have been
      considered pathogenic factors in the development of autoimmune pancreatitis.
      Besides, such autoAbs might accelerate the pancreatic damage in alcoholic chronic
      pancreatitis (CP). The aim of the present study was to evaluate the presence of
      serum Abs to CA-I and CA-II in CP and the relative affinity of these Abs. Serum
      anti-CA-I and -CA-II Abs were measured in 89 patients with CP (48 alcoholic and
      41 nonalcoholic) by an ELISA technique. The prevalence of those autoAbs in CP was
      compared with other autoimmune diseases where they have also been found. The
      presence of other serological manifestations of autoimmunity, such as
      hypergammaglobulinemia or antinuclear Abs, was determined in CP patients as well.
      Elevated serum levels of both anti-CA-I (24%) and -CA-II (18%) Abs were observed
      in CP, although their prevalence was lower than in autoimmune diseases like
      rheumatoid arthritis (44 and 25%, respectively) or systemic lupus erythematosus
      (39% for anti-CA-I Abs). Furthermore, these Abs were of low average avidity. On
      the other hand, a significantly higher proportion of nonalcoholic CP had anti-CA
      II Abs with respect to alcoholic CP (15.2 vs. 2.4%, p < 0.05). Anti-CA-I and -CA
      II Abs might be helpful in the diagnosis of autoimmune CP, and the detection of
      the latter Abs seems to discard alcoholic etiology. Although it does not discard
      any pathogenic role in autoimmune CP, the low-avidity of anti-CA Abs argues
      against such idea.

PMID- 12806142
TI  - Mitochondria: regulators of cell death and survival.
AB  - The past 5 years has seen an intense surge in research devoted toward
      understanding the critical role of mitochondria in the regulation of cell death.
      Apoptosis can be initiated by a wide array of stimuli, inducing multiple
      signaling pathways that, for the most part, converge at the mitochondrion.
      Although classically considered the powerhouses of the cell, it is now understood
      that mitochondria are also "gatekeepers" that ultimately determine the fate of
      the cell. The mitochondrial decision as to whether a cell lives or dies is
      complex, involving protein-protein interactions, ionic changes, reactive oxygen
      species, and other mechanisms that require further elucidation. Once the death
      process is initiated, mitochondria undergo conformational changes, resulting in
      the release of cytochrome c (cyt c), caspases, endonucleases, and other factors
      leading to the onset and execution of apoptosis. The present review attempts to
      outline the complex milieu of events regulating the mitochondrial commitment to
      and processes involved in the implementation of the executioner phase of
      apoptotic cell death.

PMID- 12806143
TI  - Accelerator mass spectrometry at Arizona: geochronology of the climatic record
      and connections with the ocean.
AB  - There are many diverse uses of accelerator mass spectrometry (AMS). 14C studies
      at our laboratory include much research related to paleoclimate, with 14C as a
      tracer of past changes in environmental conditions as observed in corals, marine
      sediments, and many terrestrial records. Terrestrial records can also show the
      influence of oceanic oscillations, whether they are short term, such as ENSO (El
      Nino/Southern Oscillation), or on the millennial time scale. In tracer
      applications, we have developed the use of 129I as well as 14C as tracers for
      nuclear pollution studies around radioactive waste dump sites, in collaboration
      with IAEA. We discuss some applications carried out in Tucson, AZ, for several of
      these fields and hope to give some idea of the breadth of these studies.

PMID- 12806146
TI  - Separation of membrane vesicles and cytosol from yeast, cultured cells, and
      bacteria in a small volume self-generated gradient in a fixed-angle rotor.
AB  - There are many situations when it is necessary to separate rapidly and
      efficiently a cytosolic and a membrane vesicle fraction from yeast, cultured
      cells, or from bacteria. This Protocol Article describes the flotation of the
      vesicles through a self-generated gradient from a dense sample zone using the low
      viscosity medium iodixanol. As the sample is exposed to the gmax the tendency of
      the proteins to sediment overcomes any diffusion in the opposite direction and
      are therefore completely separated from the vesicles.

PMID- 12806145
TI  - Mercury exchange at the air-water-soil interface: an overview of methods.
AB  - An attempt is made to assess the present knowledge about the methods of
      determining mercury (Hg) exchange at the air-water-soil interface during the past
      20 years. Methods determining processes of wet and dry removal/deposition of
      atmospheric Hg to aquatic and terrestrial ecosystems, as well as methods
      determining Hg emission fluxes to the atmosphere from natural surfaces (soil and
      water) are discussed. On the basis of the impressive advances that have been made
      in the areas relating to Hg exchange among air-soil-water interfaces, we analyzed
      existing problems and shortcomings in our current knowledge. In addition, some
      important fields worth further research are discussed and proposed.

PMID- 12806147
TI  - Isolation of human platelets (thrombocytes).
AB  - Platelets from human blood can be isolated in high yield by centrifugation of
      whole blood over an iodixanol density barrier of 1.063 g/ml. The separation from
      all of the blood cells (which form a pellet) is based on the slower sedimentation
      velocity of the smaller platelets.

PMID- 12806148
TI  - Sample preparation and liquid chromatography mass spectrometry analysis of
      alkylphenolic compounds and steroid sex hormones in sediments.
AB  - A new methodology, based on the use of accelerated solvent extraction (ASE) and
      highly selective cleanup using restricted access material (RAM) on-line coupled
      with liquid chromatography-mass spectrometry (LC-MS), is presented for the
      simultaneous and unequivocal determination of alkylphenol ethoxylates (APEOs),
      their degradation products and halogenated derivatives, and steroid sex hormones
      in sediment samples. Using the integrated RAM-LC-MS system, the simultaneous
      determination of alkylphenolic compounds and sex hormones was achieved, yielding
      recoveries higher than 60% and producing low MS background noise.

PMID- 12806149
TI  - Chemical analysis, distributed modelling and risk indices. Three fundamental
      pillars in Risk Assessment.
AB  - The Risk Assessment (RA) of pollutants from contaminated sites and landfills is a
      major environmental issue in Europe, due to the large number of sites and to the
      importance of groundwater protection. The high number of contaminants and the
      lack of knowledge of their environmental properties and their ecotoxicological
      and toxicological characteristics complicate the problem. Furthermore, this
      information about the chemicals has to be combined with the data relative to the
      territory and to the targets. We will describe the problems relative to each
      topic involved in the process, and we will propose an integrated methodology for
      coping with these problems, using state-of-the-art approaches in each part of the
      protocol. This methodology has been applied in several real cases.

PMID- 12806150
TI  - Homogenization of Mammalian tissues.
AB  - Satisfactory homogenization of a tissue is a necessary prerequisite to any
      fractionation schedule. A detailed protocol is given for rat liver because of the
      widespread use of this tissue. Although this technique should be broadly
      applicable to any soft tissue and to any subsequent fractionation procedure,
      there are certain tissues and applications that require either minor or extensive
      modification. Some of these points are addressed in the Notes section.

PMID- 12806151
TI  - Homogenization of mammalian cultured cells.
AB  - Satisfactory homogenization of cultured cells is a necessary prerequisite to any
      fractionation schedule. Protocols are given for homogenization in iso-osmotic (A)
      and hypo-osmotic (B) media that should be broadly applicable to any cell type and
      to any subsequent fractionation procedure. Alternative procedures are also
      summarized in the Notes section, but detailed operation of some of the automated
      devices is beyond the scope of this short Protocol Article.

PMID- 12806152
TI  - Isolation of rat and human hippocampal neuron fractions in a discontinuous
      density gradient.
AB  - The plating efficiency of neurons in culture is highly dependent on the
      concentration of cells used to establish the monolayer. A discontinuous iodixanol
      gradient permits both the production of a viable concentrated suspension of
      neurons and purification from other brain tissue elements. The gradient that is
      described in this Protocol Article is applicable to brain tissue from rat and
      also from human biopsy specimens.

PMID- 12806153
TI  - Preparation of crude subcellular fractions by differential centrifugation.
AB  - The employment of differential centrifugation to prepare crude fractions of
      subcellular particles from homogenates is often a necessary first step to a
      subsequent purification of one or more particles on a density gradient. Buoyant
      density gradient purification of peroxisomes or lysosomes for example is almost
      invariably carried out on a light mitochondrial fraction so as to eliminate
      smaller particles that may have similar densities. Unless they are first removed,
      large rapidly sedimenting particles in homogenates may also disturb shallow
      gradients designed to fractionate small low-density microsomes.

PMID- 12806154
TI  - Purification of gastric mucosal ECL cells from a crude elutriation fraction.
AB  - Acid-secreting parietal cells from the gastric mucosa are widely studied as a
      model in studies on ion transport and the endocrine/paracrine ECL cells
      effectively control parietal cell function. Discontinuous gradients of iodixanol
      for the purification of ECL cells were subsequently simplified to the use of a
      density barrier. This technique is now commonly used following initial
      centrifugal elutriation.

PMID- 12806155
TI  - Separation of human monocytes from a leukocyte-rich plasma.
AB  - Human peripheral blood monocytes are isolated by flotation from a dense leukocyte
      rich plasma (LRP) through two lower-density barriers prepared from OptiPrep. The
      separation from lymphocytes depends on the more rapid rate of flotation of the
      monocytes because of their slightly lower density and larger size. The method
      works optimally only with fresh (within 2 h of drawing) EDTA-anticoagulated
      blood.

PMID- 12806156
TI  - Purification of parietal and chief cells from the gastric mucosa.
AB  - Acid-secreting parietal cells from the gastric mucosa are widely studied as a
      model in studies on ion transport. A discontinuous gradient of iodixanol has been
      found to be superior to earlier protocols using Nycodenz and this method, which
      removes a significant amount of contaminating cells and mucus is a very useful
      prelude to further purification by elutriation.

PMID- 12806158
TI  - Purification of islets of Langerhans from porcine pancreas.
AB  - Flotation through a slightly hyperosmotic discontinuous gradient iodixanol
      achieves a much higher recovery of islets of an improved viability than the
      customary method using sedimentation on to a diatrizoate/polysaccharide barrier.
      Flotation techniques achieve an enhanced separation of the islets from any
      residual digestive enzymes and from acinar cells. The method has been extended to
      human pancreas.

PMID- 12806157
TI  - Isolation of peripheral blood mononuclear cells from macaques on a density
      barrier.
AB  - The standard techniques for the isolation of human peripheral blood mononuclear
      cells (PBMCs) using commercial "lymphocyte isolation media" cannot be
      satisfactorily extended to experimental animals without manipulating either the
      density or the osmolality of the medium. PBMCs from Macaques can also be isolated
      from whole blood by sedimentation on to a density barrier containing approx. 10%
      iodixanol, polysucrose (Ficoll) with a density of approx 1.074 g/ml.

PMID- 12806159
TI  - Purification of lipid rafts from cultured cells.
AB  - Lipid-rich lipid rafts are microdomains of the plasma membrane that are resistant
      to low concentrations of nonionic detergent. This forms the basis for their
      isolation. Either a microsomal fraction or a postnuclear supernatant are loaded
      beneath a discontinuous iodixanol gradient. If all the solutions contain 0.5-1.0%
      Triton X-100, the intact lipid rafts float to the top of the gradient while all
      of the other detergent-solubilized membranes remain at the bottom.

PMID- 12806160
TI  - Atmospheric emissions, depositions, and transformations of arsenic in natural
      ecosystem in Finland.
AB  - For the last 2 decades, special attention has been paid to arsenic due to its
      high concentration in groundwater in many regions of the globe. There are not
      very many reports on arsenic concentration in the Finnish ecosystem, although the
      metal has been known to be highly toxic since ancient times. For the majority of
      people in Finland, the leading exposure route to arsenic is through food
      consumption. In this study, it has been observed that atmospheric emissions of
      arsenic from anthropogenic sources have decreased by 90%, which is due to better
      control technology and strict regulation. Aquatic discharge also was attenuated
      from 7.1 metric tons (t) in 1990 to 0.7 t in 1999. The concentration of arsenic
      aerosols in the atmosphere in Finland varies between 0.46 to 0.75 ng m(-3). Its
      use in pesticides and insecticides also has been phased out in Finland. There is
      no information available regarding arsenic species in the Finnish environment.
      Elevated concentrations of arsenic in groundwater has been reported for many
      countries. In Finland two hot spots are reported--one in the south of Finland and
      the second in Lapland. In these areas, arsenic concentration in well water is
      greater than 10 microg l(-1) (WHO recommended value: <10 microg l(-1)). It is
      believed that the release of arsenic into the Finnish groundwater is geogenic.

PMID- 12806161
TI  - Nebivolol ameliorates nitric oxide deficient hypertension.
AB  - Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide
      (NO)-releasing properties. In the present study we have analyzed whether
      nebivolol affects the development of the arterial hypertension that follows the
      chronic inhibition of nitric oxide synthesis. Nebivolol (1 mg/kg/day, 14 days)
      was given concurrently with the NO synthesis inhibitor Nw-nitro-L-arginine methyl
      ester (L-NAME, 0.1, 1, and 10 mg/kg/day, 14 days) to several groups of rats.
      Blood pressure, renal function, plasma renin activity (PRA), and NO activity and
      metabolites were measured at the end of the treatment period. L-NAME treatment
      alone increased mean arterial pressure dose dependently (103.5 +/- 2.4, 110.9 +/-
      2.0, and 125.8 +/- 2.2 mmHg, respectively). Nebivolol completely prevented the
      development of arterial hypertension in the groups treated with L-NAME at the
      doses of 0.1 and 1 mg/kg/day and reduced the increase achieved with the L-NAME
      dose of 10 mg/kg/day (110.3 +/- 2.7). There were no differences in glomerular
      filtration rate or natriuresis between nebivolol-treated and -untreated rats.
      Plasma nitrates+nitrites and calcium-dependent NO synthase activity in the kidney
      also decreased dose dependently with L-NAME treatment and nebivolol did not
      significantly modify it. However, PRA was lower in all groups treated with
      nebivolol and L-NAME as compared to the rats receiving only L-NAME. These data
      indicate that nebivolol prevents the development of the arterial hypertension
      associated with chronic NO deficit and this effect seems to be dependent on the
      inhibition of renin-angiotensin system.

PMID- 12806163
TI  - Can early life-stages of the marine fish Sparus aurata be useful for the
      evaluation of the toxicity of linear alkylbenzene sulphonates homologues (LAS C10
      C14) and commercial LAS?
AB  - Most commercial household cleaning agents and personal care products contain the
      anionic surfactant linear alkylbenzene sulphonates (LAS) as the active compound.
      After their use they are discharged, theoretically after adequate wastewater
      treatment, into receiving waters finally reaching estuaries and coastal waters.
      Laboratory toxicity tests are useful tools in determining at which concentration
      a certain wastewater compound becomes hazardous for an existing group of
      organisms. Early life-stage toxicity tests include exposure during the most
      sensitive development period of the organism. In fish, this type of assay has
      shown to predict accurately maximum acceptable toxicant concentration (MATC)
      values (comprised in the range defined by the NOEC and LOEC) in fish early life
      stage tests. For this reason, larvae of the seabream, Sparus aurata, were exposed
      to increasing concentrations of LAS homologues (C10-C14) and commercial LAS.
      Obtained LC50 values ranged between 0.1 and 3.0 mg l(-1) and were compared with
      LC50 values of previous hatching experiments with the same species. Larvae proved
      to be more sensitive to LAS exposure of individual homologues than eggs, except
      in the case of commercial LAS. LC50 values can be directly employed to determine
      their potential risk in a concrete environment with known pollutant
      concentrations. Dividing the LC50 value with the found homologue concentration
      and extrapolating with certain security factors proposed by different
      environmental organisms, potentially hazardous pollutant concentrations may be
      detected. Average estuarine or coastal LAS concentrations are generally below
      toxicity limits for this kind of organism, considering that the average alkyl
      chain length of commercial LAS is 11.6 carbon atoms.

PMID- 12806165
TI  - Hydroxyurea treatment for sickle cell disease.
AB  - High fetal hemoglobin (HbF) levels inhibit the polymerization of sickle
      hemoglobin (HbS) and reduce the complications of sickle cell disease.
      Pharmacologic agents that can reverse the switch from gamma- to beta-chain
      synthesis--gama-globin chains characterize HbF, and sickle beta-globin chains are
      present in HbS--or selectively increase the proportion of adult erythroid
      precursors that maintain the ability to produce HbF are therapeutically useful.
      Hydroxyurea promotes HbF production by perturbing the maturation of erythroid
      precursors. This treatment increases the total hemoglobin concentration, reduces
      the vaso-occlusive complications of pain and acute chest syndrome, and attenuates
      mortality in adults. It is a promising beginning for pharmacologic therapy of
      sickle cell disease. Still, its effects are inconsistent, trials in infants and
      children are ongoing, and its ultimate value--and peril--when started early in
      life are still unknown.

PMID- 12806164
TI  - Induction of glutathione synthesis and glutathione reductase activity by abiotic
      stresses in maize and wheat.
AB  - The effect of different abiotic stresses (extreme temperatures and osmotic
      stress) on the synthesis of glutathione and hydroxymethylglutathione, on the
      ratio of the reduced to oxidised forms of these thiols (GSH/GSSG, hmGSH/hmGSSG),
      and on the glutathione reductase (GR) activity was studied in maize and wheat
      genotypes having different sensitivity to low temperature stress. Cold treatment
      induced a greater increase in total glutathione (TG) content and in GR activity
      in tolerant genotypes of both species than in sensitive ones. The GSH/GSSG and
      hmGSH/hmGSSG ratios were increased by this treatment only in the frost-tolerant
      wheat variety. High-temperature stress increased the TG content and the GSH/GSSG
      ratio only in the chilling-sensitive maize genotype, but GR activity was greater
      after this treatment in both maize genotypes. Osmotic stress resulted in a great
      increase in the TG content in wheat and the GR activity in maize. The amount of
      total hydroxymethylglutathione increased following all stress treatments. These
      results indicate the involvement of these antioxidants in the stress responses of
      wheat and maize.

PMID- 12806166
TI  - Effects of sewage sludges contaminated with chlorinated aromatic hydrocarbons on
      sludge-treated areas (soils and sediments).
AB  - The fate of PCDDs, PCDFs, and PCBs in sewage sludges after different management
      techniques--such as agricultural application, land restoration, and marine
      disposal--was studied. Changes observed in the concentrations, in the ratio
      between PCDD and PCDF levels, and in the isomeric distribution suggest the
      influence of the sewage sludge on the sludge-treated areas (soils and sediments).
      Whereas land application techniques seem to produce no serious environmental
      consequences, marine disposal practices produce considerable increases in the
      levels of contamination in marine sediments.

PMID- 12806167
TI  - Functional properties and molecular architecture of leukotriene A4 hydrolase, a
      pivotal catalyst of chemotactic leukotriene formation.
AB  - The leukotrienes are a family of lipid mediators involved in inflammation and
      allergy. Leukotriene B4 is a classical chemoattractant, which triggers adherence
      and aggregation of leukocytes to the endothelium at only nM concentrations. In
      addition, leukotriene B4 modulates immune responses, participates in the host
      defense against infections, and is a key mediator of PAF-induced lethal shock.
      Because of these powerful biological effects, leukotriene B4 is implicated in a
      variety of acute and chronic inflammatory diseases, e.g., nephritis, arthritis,
      dermatitis, and chronic obstructive pulmonary disease. The final step in the
      biosynthesis of leukotriene B4 is catalyzed by leukotriene A4 hydrolase, a unique
      bifunctional zinc metalloenzyme with an anion-dependent aminopeptidase activity.
      Here we describe the most recent developments regarding our understanding of the
      function and molecular architecture of leukotriene A4 hydrolase.

PMID- 12806168
TI  - Induction of 1-FEH in mature chicory roots appears to be related to low
      temperatures rather than to leaf damage.
AB  - Large-scale inulin production from chicory roots (Cichorium intybus L.) is
      hampered by the induction of 1-FEH activity (fructan 1-exohydrolase) and
      concomitant fructose production in autumn, coincident with a period with low
      night temperatures that cause leaf damage. To understand whether leaf damage per
      se is sufficient for 1-FEH induction and fructan breakdown, we defoliated mature
      chicory plants at a preharvest stage (September 10) and investigated the changes
      in carbohydrate levels and 1-FEH activities. Also, the activities of 1-SST
      (sucrose:sucrose 1-fructosyl transferase, EC 2.4.1.99), 1-FFT (fructan:fructan 1
      fructosyl transferase, EC 2.4.1.100), and acid invertase (EC 3.2.1.26) were
      determined. Defoliation did not result in a prompt fructan breakdown and increase
      in 1-FEH activity, but after 10 days fructan breakdown and 1-FEH activities
      became higher in the defoliated plants. Defoliation resulted in a sharp decrease
      in 1-SST activity over the first 24 h. Afterwards, root 1-SST activities of
      defoliated plants remained at a lower level than in control plants. 1-FFT and
      invertase activities were not affected by defoliation. It can be concluded that
      defoliation of plants at the preharvest stage by itself did not induce the same
      rapid changes as observed in naturally induced October roots by low temperature
      (harvest stage). Taken together with our finding that 1-FEH is not induced in
      chicory roots when plants are transferred to the greenhouse early autumn (minimal
      temperature 14 degrees C), we conclude that low temperatures might be essential
      for 1-FEH induction.

PMID- 12806169
TI  - Embryonic stem cell lines of nonhuman primates.
AB  - Human embryonic stem (ES) cell lines have opened great potential and expectation
      for cell therapy and regenerative medicine. Monkey and human ES cell lines, which
      are very similar to each other, have been established from monkey blastocysts and
      surplus human blastocysts from fertility clinics. Nonhuman primate ES cell lines
      provide important research tools for basic and applicative research. Firstly,
      they provide wider aspects of investigation of the regulative mechanisms of stem
      cells and cell differentiation among primate species. Secondly, their usage does
      not need clearance or permission from the regulative rules in many countries that
      are associated with the ethical aspects of human ES cells, although human and
      nonhuman embryos and fetuses are very similar to each other. Lastly and most
      importantly, they are indispensable for animal models of cell therapy to test
      effectiveness, safety, and immunological reaction of the allogenic
      transplantation in a setting similar to the treatment of human diseases. So far,
      ES cell lines have been established from rhesus monkey (Macaca mulatta), common
      marmoset (Callithrix jacchus), and cynomolgus monkey (Macaca fascicularis), using
      blastocysts produced naturally or by in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). These cell lines seem to have very
      similar characteristics. They express alkaline phosphatase activity and stage
      specific embryonic antigen (SSEA)-4 and, in most cases, SSEA-3. Their
      pluripotency was confirmed by the formation of embryoid bodies and
      differentiation into various cell types in culture and also by the formation of
      teratomas that contained many types of differentiated tissues including
      derivatives of three germ layers after transplantation into the severe combined
      immunodeficiency (SCID) mice. The noneffectiveness of the leukemia inhibitory
      factor (LIF) signal makes culture of primate and human ES cell lines prone to
      undergo spontaneous differentiation and thus it is difficult to maintain these
      stem cell colonies. Also, these ES cells are more susceptible to various
      stresses, causing difficulty with subculturing using enzymatic treatment and
      cloning from single cells. However, with various improvements in culture methods,
      it is now possible to maintain stable colonies of monkey ES cells using a serum
      free medium and subculturing with trypsin treatment. Under such conditions,
      cynomolgus monkey ES cell lines can be maintained in an undifferentiated state
      with a normal karyotype and pluripotency even after prolonged periods of culture
      over 1 year. Such progress should facilitate many aspects of stem cell research
      using both nonhuman primate and human ES cell lines.

PMID- 12806170
TI  - Molecular binding interactions: their estimation and rationalization in QSARs in
      terms of theoretically derived parameters.
AB  - An extensive survey of molecular binding interactions and parameters used in
      QSARs is reported, which includes consideration of lipophilicity and the
      derivation of Linear Free Energy Relationships associated with drug-receptor
      binding, together with an overview of the various contributions to binding
      energy. The lipophilic parameter, log P, and its relevance to desolvation energy
      is outlined and explanation of the parameters derived from electronic structure
      calculation is provided, leading into a summary of molecular dynamics
      simulations.

PMID- 12806172
TI  - The accumulation of deficits with age and possible invariants of aging.
AB  - This paper extends a method of apprising health status to a broad range of ages
      from adolescence to old age. The "frailty index" is based on the accumulation of
      deficits (symptoms, signs, disease classifications) as analyzed in the National
      Population Health Survey, a representative Canadian population sample (n =
      81,859). The accumulation of deficits has both an age-independent (background)
      component and an age-dependent (exponential) component, akin to the well-known
      Gompertz-Makeham model for the risk of mortality. While women accumulate more
      deficits than men of the same age, on average, their rate of accumulation is
      lower, so the difference in the level of deficits between men and women decreases
      with age. Two possible invariants of the process of accumulation of deficits were
      found: (1) the age at which the average proportion of deficits coincides for men
      and women is 94 years, which closely matches the species-specific lifespan in
      humans (95 +/- 2); (2) the value of the frailty index (proportion of deficits),
      which corresponds to that age (0.18). The similarity between mortality kinetics
      and the accumulation of deficits (frailty kinetics), and the coincidence of the
      time parameters in the frailty and mortality models make it possible to express
      mortality risk in terms of accumulated deficits. This provides a simple and
      accessible tool that might have potential in a number of biomedical applications.

PMID- 12806171
TI  - High dose cyclophosphamide treatment for autoimmune disorders.
AB  - High-dose cyclophosphamide (200 mg/kg) was initially developed as a conditioning
      regimen for allogeneic bone marrow transplantation. Recently, high-dose
      cyclophosphamide without bone marrow transplantation has been employed as a
      method to induce durable treatment-free remissions in severe aplastic anemia and
      a variety of other severe autoimmune disorders. The premise underlying this
      approach is that high-dose cyclophosphamide is maximally immunosuppressive, but
      not myeloablative. Early hematopoietic stem cells are spared the cytotoxicity of
      cyclophosphamide because of their high levels of aldehyde dehydrogenase, an
      enzyme that confers resistance to the drug. Conversely, autoimmune effector cells
      (T cells, B cells, and NK cells) are exquisitely sensitive to high-dose
      cyclophosphamide because of their relatively low levels of aldehyde
      dehydrogenase. Intensive investigation is underway to determine which autoimmune
      disorders will most benefit and where in the natural history of these diseases to
      employ this rapidly developing therapy.

PMID- 12806173
TI  - Semisynthesis of ribonuclease A using intein-mediated protein ligation.
AB  - The introduction of non-natural amino acid residues or modules into proteins
      provides a new means to explore the basis for conformational stability,
      folding/unfolding behavior, or biological function. We exploited intein-mediated
      protein ligation to produce a semisynthetic ribonuclease A. Of the 124 residues
      of RNase A, residues 1-94 were linked to an intein. After expression of the
      fusion protein and thiol-induced cleavage, the RNase A(1-94) fragment possessed a
      C-terminal thioester. A peptide identical to the C-terminal residues 95-124 of
      RNase A (with residue 95 being cysteine) was successfully ligated to that
      thioester thereby reconstituting full-length wild-type RNase A. In mass
      spectrometry, this semisynthetic RNase A proved to be undistinguishable from the
      control protein, namely recombinant wild-type RNase A. Recombinant wild-type
      RNase A was obtained by expression of RNase A(1-124)-intein fusion protein
      followed by thiol-induced cleavage and hydrolysis of the thioester. Both proteins
      showed thermal stabilities (Tm) and catalytic activities comparable to the wild
      type enzyme, indicating that both proteins folded properly. These results might
      serve as basis for the semisynthesis of RNase A variants containing non-natural
      modules in the aforementioned peptide.

PMID- 12806174
TI  - Gonadotropin-releasing hormone activates the 12-lipoxygenase pathway in the
      LbetaT2 gonadotrope cell line.
AB  - Previous studies have indicated that arachidonic acid and its lipoxygenase (LO)
      metabolites play a role in the post-receptor effects of gonadotropin-releasing
      hormone (GnRH) but the exact role and nature of these putative eicosanoids remain
      unclear. The potential role of arachidonic acid and LO in GnRH receptor-mediated
      signaling was investigated in the LbetaT2 gonadotrope cell line, which expresses
      gonadotropins (LH and FSH) and GnRH-receptor mRNAs. Western immunobloting of
      LbetaT2 cell extracts, performed with a murine leukocyte polyclonal antibody
      against 12-LO, showed a 70-kD band, suggesting the presence of 12-LO protein in
      these cells. GnRH nearly doubled the release of 12-hydroeicosatetraenoic acid, a
      product of the 12-LO enzyme, within 10 min. A specific reverse transcriptase
      polymerase chain reaction with a set of primers based on the reported sequence of
      rat brain 12-LO yielded a 170-bp band which showed 100% homology with the
      expected rat brain 12-LO sequence. Exposure of LbetaT2 cells to pulsatile GnRH
      treatment (10 nM, 90-min interpulse, one and three pulses) led to a approximately
      3-fold increase in 12-LO mRNA levels. In conclusion, we provide evidence for the
      presence of a 12-LO enzyme in LbetaT2 cells, the expression and activity of which
      are increased by short-term/pulsatile exposure to GnRH. LbetaT2 cells represent a
      potential model to further study the involvement of 12-LO in GnRH receptor
      signaling.

PMID- 12806175
TI  - Regulation of follicle-stimulating hormone secretion by the interactions of
      activin-A, dexamethasone and testosterone in anterior pituitary cell cultures of
      male rats.
AB  - This study was designed to evaluate the effects of glucocorticoids and gonadal
      steroids on the expression of inhibin/activin subunits and follistatin of the
      anterior pituitary and test the hypothesis that resulting changes in the local
      activin/inhibin/follistatin tone contribute to steroid effects on follicle
      stimulating hormone (FSH) production from gonadotropes. In primary cell cultures
      of male rat anterior pituitaries, dexamethasone (DEX) or testosterone (T)
      stimulated FSH secretion and FSHbeta mRNA and their effects were additive with
      activin-A. Follistatin (FS288) and inhibin-A antagonized the rise in FSH
      secretion both in the absence and presence of exogenous activin-A. Despite the
      similarity in their action on FSH production, DEX and T had opposite effects on
      follistatin mRNA levels. Follistatin mRNA levels of cultured rat anterior
      pituitary cells were elevated upon the addition of DEX but attenuated by T. On
      the other hand, both DEX and T suppressed inhibin/activin betaB mRNA levels while
      only DEX affected betaA mRNA. In these cells, activin-A stimulated follistatin
      and inhibin/activin betaB mRNA levels but had no effect on betaA. Together, DEX
      and activin-A caused a further increase in follistatin mRNA levels while T
      attenuated the effect of activin-A alone. Both steroids attenuated the effect of
      activin-A on betaB mRNA accumulation. These results support the possibility that
      DEX and T, possibly acting on different subsets of anterior pituitary cells, use
      distinct mechanisms to modify the local activin/inhibin/follistatin circuitry and
      thereby upregulate FSH production from the anterior pituitary gonadotropes.

PMID- 12806176
TI  - c-FOS expression in the forebrain after mating in the female rat is altered by
      adrenalectomy.
AB  - In rats of both sexes, mating stimulates neuronal activity in forebrain areas
      that are also activated by stress. Hypothalamic cells in the arcuate (ARC) and
      paraventricular (PVN) nuclei synthesize hormones or peptides whose levels are
      altered by adrenalectomy. In this experiment, we examined whether the mating
      induced expression of c-FOS in the forebrain is altered by adrenalectomy (Adx) in
      female rats. Ovariectomized females were adrenalectomized (Adx) or sham-operated
      (Sham), hormone-primed and mated 2 weeks after surgery. They received 15
      intromissions (15I), 5 intromissions (5I) or 15 mounts without intromission (MO)
      from a male or were taken directly from their home cage (HC). Two hours after
      mating, rats were perfused with paraformaldehyde and their brains were collected
      and stained immunocytochemically for FOS protein. FOS-immunoreactive (FOS-IR)
      cells in the posterodorsal medial amygdala (MePD), bed nucleus of stria
      terminalis (BNST), ventromedial hypothalamus (VMH), medial preoptic area (mPOA),
      ARC and PVN were counted bilaterally. In Sham animals, intromissions produced
      significant increases in FOS above HC levels. In Adx animals, mating increased
      FOS activity in all areas. However, responses to 5I and 15I differed between Sham
      and Adx groups. In all areas, Shams showed either the highest FOS response
      following 15I or levels which were equivalent after 5I and 15I. In Adx animals,
      the greatest number of FOS-positive cells occurred after 5I, with the 15I group
      showing significant suppression of FOS below 5I levels in the VMH, mPOA, ARC and
      PVN. These results demonstrate that the adrenal modulates FOS responses to mating
      in the female rat and suggest that adrenal secretory products normally may
      decrease sensitivity to low levels of mating stimulation. These effects may be
      due to increased corticotropin-releasing hormone (CRH) or beta-endorphin in the
      hypothalamus after adrenalectomy.

PMID- 12806177
TI  - Evidence for a GABAergic system in rodent and human testis: local GABA production
      and GABA receptors.
AB  - The major neurotransmitter of the central nervous system, gamma-aminobutyric acid
      (GABA), exerts its actions through GABA(A), GABA(B) and GABA(C) receptors. GABA
      and GABA receptors are, however, also present in several non-neural tissues,
      including the endocrine organs pituitary, pancreas and testis. In the case of the
      rat testis, GABA appears to be linked to the regulation of steroid synthesis by
      Leydig cells via GABA(A) receptors, but neither testicular sources of GABA, nor
      the precise nature of testicular GABA receptors are fully known. We examined
      these points in rat, mouse, hamster and human testicular samples. RT-PCR followed
      by sequencing showed that the GABA-synthesizing enzymes glutamate decarboxylase
      (GAD) 65 and/or GAD67, as well as the vesicular GABA transporter vesicular
      inhibitory amino acid transporter (VIAAT/VGAT) are expressed. Testicular GAD in
      the rat was shown to be functionally active by using a GAD assay, and Western
      blot analysis confirmed the presence of GAD65 and GAD67. Interstitial cells, most
      of which are Leydig cells according to their location and morphological
      characteristics, showed positive immunoreaction for GAD and VIAAT/VGAT proteins.
      In addition, several GABA(A) receptor subunits (alpha1-3, beta1-3, gamma1-3), as
      well as GABA(B) receptor subunits R1 and R2, were detected by RT-PCR. Western
      blot analysis confirmed the results for GABA(A) receptor subunits beta2/3 in the
      rat, and immunohistochemistry identified interstitial Leydig cells to possess
      immunoreactive GABA(A) receptor subunits beta2/3 and alpha1. The presence of
      GABA(A) receptor subunit alpha1 mRNA in interstitial cells of the rat testis was
      further shown after laser microdissection followed by RT-PCR analysis. In
      summary, these results describe molecular details of the components of an
      intratesticular GABAergic system expressed in the endocrine compartment of rodent
      and human testes. While the physiological significance of this peripheral
      neuroendocrine system conserved throughout species remains to be elucidated, its
      mere presence in humans suggests the possibility that clinically used drugs might
      be able to interfere with testicular function.

PMID- 12806178
TI  - Morphological studies of prolactin-secreting cells in estrogen receptor alpha and
      estrogen receptor beta knockout mice.
AB  - Estrogens play a major role in the regulation of prolactin (PRL) secretion
      through activation of pituitary and hypothalamic estrogen receptors (ERs). In
      order to evaluate the relative role of ERalpha and ERbeta in the control of PRL
      density in the pituitary gland, we performed immunocytochemical localization of
      PRL and ERs in pituitaries of wild-type (WT), ERalpha knockout (KO) and ERbetaKO
      mice. In WT and ERbetaKO anterior pituitaries, the vast majority of secretory
      cells contained ERalpha immunoreactivity, while no ERalpha immunostaining could
      be found in ERalphaKO pituitaries. No ERbeta immunoreactivity could be detected
      in pituitaries of WT, ERalphaKO or ERbetaKO mice. At the light microscopic level,
      a large number of cells staining for PRL were present in pituitaries of female
      WT, while in female ERalphaKO pituitaries, the density of PRL cells was much
      lower. In WT male pituitaries, the density of PRL cells was lower than observed
      in female WT, while PRL staining was markedly decreased in male ERalphaKO as
      compared to male WT. In ERbetaKO mice of both sexes, the results were identical
      to those observed in WT animals. At the electron microscopic level, in WT mice of
      both sexes, type 1 PRL cells exhibited a well-developed Golgi apparatus and a
      large number of strongly stained large mature and immature secretory granules.
      Type 2 PRL cells were also present in the pituitary. Type 2 PRL cells contain
      small poorly labelled granules. In ERalphaKO mice of both sexes, type 1 PRL cells
      were atrophied with poorly developed Golgi apparatus, and no type 2 PRL cells
      could be observed. In ERalphaKO pituitaries, typical gonadectomy cells were
      found. No ultrastructural changes were observed in PRL cells of ERbetaKO mice.
      The present data strongly suggest that the positive regulation of PRL expression
      at the pituitary level by estrogens is mediated by ERalpha and does not involve
      ERbeta activation.

PMID- 12806179
TI  - Differential expression of estrogen receptors alpha and beta in the spinal cord
      during postnatal development: localization in glial cells.
AB  - Estrogens are recognized as neuroprotective and neurotrophic agents in the
      central nervous system. They are involved in neuronal differentiation and
      survival and promote neural development. Estrogen receptors alpha (ER-alpha) and
      beta (ER-beta) are predominantly expressed in neurons, whereas their presence in
      glial cells in vivo is more controversial. Changes in their expression during
      development have been described in different brain areas, but little is known
      about their presence in the spinal cord. We have carried out an
      immunohistochemical study in an attempt to analyze the expression of both ERs in
      astrocytes and oligodendrocytes of the rat spinal cord and their modifications
      during postnatal development. RT-PCR analysis of whole spinal cord extracts from
      4-, 12-, and 25-day-old and adult rats indicated changes in the expression of
      both receptors during maturation. Immunohistochemistry of slices of the lumbar
      tract revealed that in an area of the ventral spinal cord that does not contain
      neuronal cell bodies, but mainly fibers and glial cells, both ER-alpha and ER
      beta can be detected. Immunostaining is clearly nuclear, and, in the case of ER
      alpha, both markedly positive and weakly labeled cells can be identified. ER
      alpha is expressed during early development to progressively decline in the adult
      stage. In contrast, the ER-beta signal is low and peaks at postnatal day 25,
      whereas it is almost undetectable at other ages. Colocalization studies revealed
      that, at postnatal day 25, ER-alpha and ER-beta are expressed in astrocytes
      (identified by the specific marker glial fibrillar acidic protein) and
      oligodendrocytes (labeled by antimyelin 2',3'-cyclic nucleotide 3'
      phosphodiesterase). The present results confirm the expression of ER-alpha and ER
      beta in glial cells in vivo and suggest that, also in the spinal cord, glial
      cells may contribute to the effects of estrogen during development.

PMID- 12806180
TI  - Involvement of vasoactive intestinal peptide on insulin-like growth factor I
      induced proliferation of rat pituitary lactotropes in primary culture: evidence
      for an autocrine and/or paracrine regulatory system.
AB  - In previous studies we demonstrated that insulin-like growth factor I (IGF-I)
      induces pituitary vasoactive intestinal peptide (VIP) gene expression and
      secretion, and that IGF-I-induced prolactin (PRL) release is mediated by VIP. In
      this study, we investigate the mitotropic action of IGF-I and VIP on pituitary
      lactotropes, and their possible interplay in this effect. Cultured male rat
      pituitary cells were treated with rhIGF-I (10(-7)M) and/or VIP (10(-7)M) for 48
      h. 5-Bromo-2'-deoxyuridine (BrdU) (10 microM) was added for labeling
      proliferation of pituitary cells. BrdU-labeling indices indicative of the
      proliferation rate of lactotropes were determined by double-labeling
      immunofluorescence staining for PRL and BrdU. Treatment with either IGF-I or VIP
      increased BrdU-labeling indices of lactotropes, but there was no further increase
      upon combined incubation with both factors, suggesting an interaction between the
      signal transduction pathways of IGF-I and VIP. VIP antiserum partially suppressed
      IGF-I-induced BrdU-labeling indices of lactotropes. We also investigated the
      intracellular signal transduction pathways in the action of IGF-I and VIP on the
      proliferation of lactotropes. Treatment of pituitary cells with an inhibitor of
      the mitogen-activated protein kinase (MAPK) pathway completely abolished IGF-I
      induced lactotrope proliferation, whereas it partially suppressed VIP-induced
      BrdU-labeling indices. The protein kinase A (PKA) inhibitor, which abolished the
      mitogenic action of VIP, markedly suppressed IGF-I-induced lactotrope
      proliferation. These results indicate that both IGF-I and VIP stimulate
      lactotrope proliferation, and that IGF-I-induced lactotrope proliferation is
      partially mediated by VIP produced locally. Also, this study suggests that
      interactions between MAPK and cyclic adenosine 3',5'-monophosphate-PKA signaling
      pathways are implicated in the lactotrope proliferation induced by IGF-I and VIP.

PMID- 12806181
TI  - Following the expression of a kidney-specific gene from early development to
      adulthood.
AB  - Ksp-cadherin (Cadherin 16) is a unique, tissue-specific member of the cadherin
      family of cell adhesion proteins that is expressed exclusively in tubular
      epithelial cells in the adult kidney and developing genitourinary (GU) tract.
      Since its original identification in 1995, Ksp-cadherin has proven to be a useful
      experimental model for studies of kidney-specific and developmental gene
      regulation. These investigations have led to the creation of new strains of
      transgenic mice that will be useful for studies of renal cell lineage and tissue
      specific gene targeting. Recent studies have also identified Ksp-cadherin as the
      first kidney-specific promoter that it is regulated by HNF-1beta (hepatocyte
      nuclear factor-1beta), a transcription factor that has been implicated in human
      renal cystic disease.

PMID- 12806182
TI  - Intravital imaging of the kidney using multiparameter multiphoton microscopy.
AB  - Intravital optical microscopy provides a powerful means of studying the cell
      biology in the most physiologically relevant setting. The ability of multiphoton
      microscopy to collect optical sections deep into biological tissues has opened up
      the field of intravital microscopy to high-resolution studies of multiple organs.
      Presented here are examples of how two-photon microscopy can be applied to
      intravital studies of kidney physiology and the study of disease processes. These
      include studies of cell vitality and apoptosis, fluid transport, receptor
      mediated endocytosis, blood flow, and leukocyte trafficking. Efficient two-photon
      excitation of multiple fluorophores permits comparison of multiple probes and
      simultaneous characterization of multiple parameters. Two-photon microscopy can
      now provide a level of investigation previously unattainable in intravital
      microscopy, enabling kinetic analyses and physiological studies of the organs of
      living animals with subcellular resolution. Therefore, application of this
      technology will provide direct visualization of organ-specific and cell-specific
      responses to an array of stimuli and therapeutic approaches, enhancing our
      understanding and treatment of disease processes.

PMID- 12806183
TI  - Tissue trace element change after total body irradiation.
AB  - PURPOSE: In this study, we examined the changes of tissue contents of trace
      elements and iron after total body irradiation (TBI) and their possible impact on
      late toxicities. MATERIAL AND METHODS: 20 female Wistar rats were randomly
      assigned to two groups - either radiation (n = 10) or control (n = 10). Rats in
      the radiation group received TBI of 5 Gy in a single fraction. Rats were
      sacrificed and tissue samples of heart, lung and kidney were taken 8 weeks after
      radiation. Tissue levels of zinc, copper, magnesium, manganese and iron analysis
      were performed with an atomic absorption spectrophotometer and suprapure grade
      standard solutions. One kidney of each animal was taken for electron microscopic
      analysis. Blood samples were collected from all animals and the blood chemistry
      related to kidney function was studied. RESULTS: The kidney levels of Fe and Cu
      significantly increased 8 weeks after irradiation (p < 0.05). The Cu/Zn ratio did
      not reach statistical significance in any tissue, however in kidney, there was a
      tendency to rise (p = 0.08). Myocardium and lung content of trace elements and
      iron did not show any significant change 8 weeks after irradiation. Electron
      microscopic analysis showed significant injury in glomerular endothelial cells,
      renal tubules and thickening of basement membrane. Blood chemistry showed a
      significant rise in serum creatinine (p = 0.008) and calcium (p = 0.01) in the
      TBI group. Serum creatinine levels were 0.73 and 0.84 mg/dl, and serum calcium
      levels were 10.1 and 11.3 mg/dl in control and TBI groups, respectively.
      CONCLUSION: A sublethal dose of TBI causes deposition of Cu and Fe within the
      kidney after TBI. Deposition of these elements may have some additional role on
      the toxicity caused by direct radiation on the kidney.

PMID- 12806184
TI  - Role of cytochrome P450 2B1 in puromycin aminonucleoside-induced cytotoxicity to
      glomerular epithelial cells.
AB  - Puromycin aminonucleoside (PAN)-induced glomerular injury in rats mimics minimal
      change nephrotic syndrome (NS) in humans. We have demonstrated an important role
      of cytochrome P450 (CYP) as a significant source of catalytic iron in this model
      of NS. The current study was designed to identify CYP isozyme(s) present in the
      rat glomerular epithelial cells (GEC) and to explore the role of the specific CYP
      isozyme in PAN-induced cytotoxicity. CYP2B1 was identified in GEC by
      immunocytochemistry and Western blot. Treatment of GEC with PAN resulted in a
      marked generation of hydrogen peroxide (H(2)O(2)) and reduction of CYP2B1 content
      associated with significant increase in catalytic iron and hydroxyl radical
      formation. Preincubating GEC with CYP2B1 inhibitors (piperine and cimetidine) and
      H(2)O(2) scavenger (pyruvate) significantly reduced H(2)O(2 )generation,
      preserved CYP2B1 content, prevented the increase in catalytic iron and hydroxyl
      radical formation including PAN-induced cytotoxicity. We also observed the
      induction of heme oxygenase (HO-1) in PAN-treated GEC, and this up-regulation was
      reduced by pretreatment of the CYP inhibitors and pyruvate. Our data thus
      indicate an important role of CYP2B1 in PAN-induced cytotoxicity by serving as a
      site of reactive oxygen metabolite generation and a significant source of
      catalytic iron.

PMID- 12806185
TI  - Epitope mapping of monoclonal antibodies directed to aminopeptidase A and their
      relevance for albuminuria in mice.
AB  - We have shown previously that injection of specific combinations of anti
      aminopeptidase A monoclonal antibodies induces an acute massive albuminuria in
      mice. This albuminuria is neither dependent on systemic mediators of inflammation
      nor angiotensin II. In this study, we examined the contribution of two individual
      antibodies, the enzyme-inhibiting antibody ASD-37 and the non-enzyme-inhibiting
      antibody ASD-41, in the induction of albuminuria as well as the interactions
      between these two monoclonals. In addition, we have mapped the epitopes of both
      antibodies using in vitro coupled transcription/translation of specifically
      designed cDNA fragments followed by immunoprecipitation, and using peptide enzyme
      linked immunosorbent assay in case of a continuous epitope. A single intravenous
      injection of 4 mg of either ASD-37 or ASD-41 did not induce albuminuria. This
      dose of ASD-37 did not completely inhibit enzyme activity. The combination of 4
      mg ASD-37/41 (1:1 weight ratio) induced albuminuria and almost completely
      inhibited enzyme activity. Similar results were obtained with a combination of
      ASD-37/41 in a 1:39 or 39:1 weight ratio. Administration of 2 mg ASD-41 24 h
      before injection of 2 mg ASD-37 significantly enhanced albuminuria. The epitope
      of ASD-37 is located at the C-terminal end of aminopeptidase A, whereas the ASD
      41 epitope is mapped near the enzyme active site. Our data suggest that ASD-41
      modulates the binding of ASD-37 to its epitope and/or vice versa. As a
      consequence, ASD-37 and ASD-41 act synergistically, not only in inhibiting enzyme
      activity but also in inducing albuminuria.

PMID- 12806186
TI  - On the horizon: tailor-made immunosuppression in renal transplantation.
AB  - Immunosuppression for renal transplantation has undergone more changes over the
      last 8 years than at any other time in its history. It is now possible to be more
      selective in the matching of drugs with a given patient. This brings with it the
      option of improving graft outcome and also minimizing adverse effects. It is an
      ongoing process that will utilize agents working at different points in the
      activation cascade of the CD4+ 'helper' T lymphocyte. It may also be possible to
      manipulate the immune system such that the organ-specific immune response may be
      switched off, or rendered 'tolerant', thus removing the need for any
      immunosuppressive drugs. In this brief review, we shall address each of these
      approaches and discuss other therapeutic avenues being investigated.

PMID- 12806187
TI  - Atheroembolic renal failure requiring dialysis: potential for renal recovery? A
      review of 43 cases.
AB  - AIMS: Our objectives were to review the characteristics of patients who developed
      atheroembolic renal disease requiring dialysis as well as their renal function
      recovery and survival rates. METHODS: All cases of atheroembolic disease with
      renal failure severe enough to require dialysis were reviewed from January 1984
      to December 2000 in two centers. The diagnosis of atheroemboli was based on
      clinical presentation and/or biopsy. Acute renal failure was defined as a serum
      creatinine >200 micromol/l if normal at baseline or doubling from baseline if
      chronic renal failure, whereas renal function recovery was the ability to
      discontinue renal replacement therapy for >or=3 months. RESULTS: Forty-three
      cases were identified (37 males and 6 females; mean age 67 +/- 5 years); the
      average time to acute renal failure and to diagnosis was similar at 36 days. The
      majority of patients had at least one precipitating factor identified (58%
      coronary angiography, 26% angiography, 16% vascular surgery, 2% anticoagulation);
      1 had a spontaneous presentation whereas 7 had more than one factor. More than
      90% had underlying hypertension and chronic renal dysfunction with a baseline
      creatinine of 195 +/- 81 micromol/l, approximately 80% had coronary artery
      disease, 80% were smokers, 60% had a history of abdominal aorta aneurysm, >50%
      presented with intermittent claudication, and 56% were anticoagulated at the time
      of the event. Most patients were nonoliguric (80%), had increased hypertension
      (71%), blue toes (67%), livedo reticularis (52%), whereas abdominal pain and
      central nervous system symptoms were present in 33 and 7% of the cases,
      respectively. Eosinophilia was found in 88%, while hypocomplementemia was present
      in less than 15%. When compared to the 12 patients with recovery of renal
      function (after a mean delay of 409 +/- 336 days), the 31 patients who did not
      recover function presented with more severe intermittent claudication and
      underlying chronic renal dysfunction (p < 0.05). Indeed, the only variable found
      to unfavorably influence renal function recovery was the presence of intermittent
      claudication. Patients were mainly treated by intermittent hemodialysis except
      for 5 (2 on CRRT and 3 on peritoneal dialysis). Renal function recovery was
      associated with a higher chance of survival; 33% of patients died in the first
      year after diagnosis. CONCLUSION: Atheroembolic renal disease carries a high
      mortality rate reflective of the extensive cardiovascular disease of affected
      patients; nevertheless, the potential for renal function recovery appears greater
      than for other vascular causes of renal failure.

PMID- 12806188
TI  - Non-invasive monitoring of renal transplant recipients: urinary excretion of
      soluble adhesion molecules and of the complement-split product C4d.
AB  - BACKGROUND: The number of inducible adhesion molecules known to be involved in
      cell-mediated allograft rejection is still increasing. In addition, recent data
      describe complement activation during acute humoral allograft rejection. The aim
      of this study was to assess whether specific molecules from either pathway are
      excreted into urine and whether they can provide useful diagnostic tools for the
      monitoring of renal transplant recipients. METHODS: Urinary concentrations of
      soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation
      product C4d were determined by standardized ELISA technique in 75 recipients of
      renal allografts and 29 healthy controls. Patient samples were assigned to four
      categories according to clinical criteria: GROUP 1: acute steroid-sensitive
      rejection (ASSR, n = 14), GROUP 2: acute steroid-resistant rejection (ASRR, n =
      12), GROUP 3: chronic allograft dysfunction (CAD, n = 20) and GROUP 4: stable
      graft function (SGF, n = 29). RESULTS: All patients with rejection episodes
      (groups 1-3) had significantly higher values of urinary sC4d compared with
      healthy controls and patients with stable graft function (p < 0.05). The urinary
      levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all
      other groups (p < 0.001). Uniformly low amounts of s-VCAM-1 and complement-split
      product C4d were excreted by healthy controls (group 0). In contrast, urinary
      sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR)
      whereas patients with a stable functioning graft (group 4) excreted significantly
      less sICAM-1 (p < 0.05). CONCLUSION: The evaluation of sVCAM-1 and sC4d excretion
      in urine can provide a valuable tool with regard to the severity and type of
      allograft rejection. With respect to long-term allograft survival, serial
      measurements of these markers should have the potential to detect rejection
      episodes and prompt immediate treatment.

PMID- 12806189
TI  - [The Gynecologic and Obstetric Review (Gynaekologisch-geburtshilfliche Rundschau)
      faces a new challenge!].
AB  - The Austrian Society of Gynecology and Obstetrics gave notice of organ membership
      and at the same time of the compulsory subscription to the Gynecologic and
      Obstetric Review/ Gynakologisch-geburtshilfliche Rundschau in favor of a journal
      oriented more towards professional politics. Thus ends a long-standing
      international tradition. This also means a new challenge for the Gynecologic and
      Obstetric Review/Gynakologisch-geburtshilfliche Rundschau.

PMID- 12806190
TI  - [Child and adolescent gynecology. Introduction to the focal topic 'Child and
      adolescent gynecology'].
AB  - Valuable knowledge from the subspecialty of child and adolescent gynecology is of
      considerable importance for the clinically active pediatrician and gynecologist.
      Focal topics such as sexual violence to children and young adults, undesired
      pregnancies and pregnancy termination should not only be made known in the media,
      but also to specialists, so that successful prevention and treatment can be
      carried out. Furthermore, endocrinological problems and genital malformations in
      adolescence should be detectable and treatable.

PMID- 12806191
TI  - [The importance of a gynecological teenager consulting hour by the example of
      "First Love"].
AB  - There are worldwide deficits in sexual and contraceptive education of teenagers
      and the effects on their contraceptive behaviour. It is worthwhile to offer
      services tailored to the needs of adolescent girls. This can be demonstrated by
      the experience of 10 years work of 'First Love', a gynaecological out-patient
      department for teenagers at Rudolfstiftung Hospital, Vienna. Together with the
      girls and their partners, individual concepts for safe, responsible and
      satisfying sexuality are developed. A multidisciplinary team, easy access, the
      possibility of remaining anonymous and free-of-charge consultations are the major
      principles in this work. There are also a lot of preventive health care issues:
      as young girls experience their first gynaecological examination as painless and
      less embarrassing than expected, they will agree to routine check-ups in their
      future life.

PMID- 12806192
TI  - [Abnormalities of external and internal genitalia].
AB  - The gynecologic examination of the female genitalia of children and young adults
      belongs in the hands of specialists and should be performed in the appropriate
      environment. The most important task of such an examination is the distinction
      between true developmental anomalies and anatomical findings mimicking such
      anomalies. Even newborn females can be successfully examined without any large
      effort expenditure. In most cases, the external inspection of the vestibule is
      enough to reach a diagnosis. In other case scenarios, vaginoscopy and
      gynecological speculum examination may be necessary. Additional imaging studies
      include abdominal sonography and magnetic resonance imaging. Normal variations of
      a child's hymenal membrane, fusion of the labia minora, hymenal polyps and
      hypertrophy of the preputium of the clitoris are the entities most likely to be
      mistaken for real developmental malformations. The most important asymptomatic
      developmental anomaly of the vagina and the uterus is the Mayer-Rokitansky-Kuster
      Hauser syndrome (uterine and vaginal agenesis). Developmental malformations, such
      as hymenal atresia, vaginal septum formation and Millerian anomalies in general,
      tend to be symptomatic, presenting with hematometra, hematocolpos or
      dysmenorrhea. The treatment of genital developmental anomalies is generally not
      difficult but requires the appropriate clinical and surgical expertise.

PMID- 12806193
TI  - [Sexual abuse in adolescence: patient assessment, necessity and meaning of the
      physical examination].
AB  - The objective of this paper is to report on the characteristics of sexual abuse
      in adolescence, on the medical evaluation and interpretation of findings and on
      the necessity of a multidisciplinary intervention. Sexual abuse is a common
      problem affecting children and adolescents, males and females of any age or socio
      economic class. 10-22% of adolescents are victims of sexual abuse. They engage
      more frequently in risk-taking behaviours, such as early sexual activity,
      unprotected sexual contact with multiple partners (risk of sexually transmitted
      diseases, of an unwanted pregnancy), substance abuse, delinquency, school failure
      or suicide. Professionals who deal with adolescents should be aware of the
      devastating medical and psychosocial sequelae of sexual abuse and should be able
      to recognize it, incorporating questions regarding victimization into the psycho
      social or sexual history. A medical examination, including an external anogenital
      inspection and in selected cases a pelvic examination, should always be
      performed. It is important to acknowledge that normal anogenital findings do not
      exclude sexual abuse and that a multidisciplinary medical-psychosocial evaluation
      is mandatory.

PMID- 12806194
TI  - [Hormonal disorders, menstrual irregularities and future fertility].
AB  - Menstrual irregularities are common in puberty and adolescence during the
      development of ovarian function and until a regular ovulatory cycle is
      established. Hormonal disorders should be investigated promptly to avoid or
      alleviate possible long-term sequelae, including impaired fertility. Most
      irregularities are transient and self-limited, but some are severe or prolonged
      and require exploration and treatment. Symptoms such as prolonged oligomenorrhea
      andoligoamenorrhea may herald an incipient or preexisting endocrinopathy. An
      exact diagnosis by estimation of the hormonal parameters can identify a relevant
      disturbance. The prognosis for later fertility in patients with oligoamenorrhea
      depends on the etiology and degree of the condition. With a hypothalamic origin
      the prognosis is good when the offending stimuli are removed. Patients with
      pituitary lesions or hyperprolactinemia can be treated effectively. Hyper
      androgenemic oligoamenorrhea, especially the polycystic ovarian syndrome, are
      common. Future fertility is reduced but may be improved by preventive measures
      and therapy in adolescence. Inpatients with primary ovarian insufficiency and
      persisting hyper-gonadotropic amenorrhea, the prognosis for fertility is poor.

PMID- 12806195
TI  - [Maternal mortality in Switzerland 1985-1994].
AB  - The maternal mortality rate in the west has dropped drastically in the last 100
      years. As yet there are no detailed numbers of the actual causes of death for
      Switzerland. We re-evaluated the anonymous patient documentation for the years
      1985-1994 using the officially registered (ICD-8) cases of maternal mortality. 45
      deaths out of 812,825 births remained from the original 76 registered cases,
      which corresponds to a direct maternal mortality of 5.4/100,000 live births. The
      other cases had to be reclassified (indirect, late or pregnancy-related obstetric
      deaths). The majority of the deaths were caused by thromboembolism (15%). The
      mortality rate for cesarean section was 0.09 per thousand. The large number of
      reclassified cases shows that further teaching is necessary in the completion of
      the death certificate. In the attempt to reduce maternal mortality, one has to
      direct attention to the consequent prophylaxis of thromboembolism and induce a
      premature birth in cases of HELLP syndrome.

PMID- 12806196
TI  - Portal venous gas detected by computed tomography: is surgery imperative?
AB  - BACKGROUND: Portal vein gas (PVG) has historically been associated with mortality
      rates of 75% or higher and mandatory abdominal exploration. The following study
      reassesses the clinical significance of gas in the portal venous system detected
      by computed tomography (CT) and reevaluates the need for surgical intervention in
      that setting. METHODS: We performed a retrospective chart review of 26 patients
      presenting with gas in the portal venous system as imaged by CT between August 1,
      1993 and April 8, 2001. Characteristics assessed included age, sex, clinical
      presentation and course, additional CT findings, diagnosis, surgical versus non
      surgical management, surgical findings, pathologic correlation, and mortality.
      RESULTS: Of the 26 patients who had gas in the portal venous system by CT, 11
      underwent surgery to determine underlying pathology. Of those who underwent
      surgery, 8 survived to be discharged while 3 died (73% surgical survival). The
      survivors presented with gastrointestinal related signs/symptoms and were found
      at the time of surgery to have adhesions, non-surgically treated inflammation,
      unclear pathology, or resectable lesions. Those who died all demonstrated marked
      bowel ischemia intraoperatively. Among patients who did not undergo surgery, 9
      survived and 6 died (60% nonsurgical survival). Those who survived presented
      either asymptomatically or with pathology including acute pancreatitis, recent
      hypotensive episode, uncomplicated diverticulitis, unresectable colon cancer, or
      infectious etiology. Those who died were poor surgical candidates or status
      postvascular procedure. The overall survival in patients with portal venous gas
      by CT was 65%. CONCLUSION: Portal venous gas on CT is associated with a wide
      range of pathologies that do not necessarily warrant surgical management.
      Clinical presentation should be correlated with the presence of PVG and other
      associated CT findings prior to deciding whether surgery should be performed.

PMID- 12806197
TI  - Mortality after colon surgery: the value of a mortality registration system.
AB  - BACKGROUND/AIMS: Postoperative mortality after colon surgery is relatively
      infrequent. In order to evaluate the quality of colon surgery, post-mortem
      evaluation is useful. This study was performed to determine the value of a
      mortality register used at the Department of Surgery of the Red Cross Hospital.
      METHODS: From 1991 to 2000, 882 colon resections were performed for both
      malignant and benign disorders, including elective and emergency surgery.
      Permission for autopsy was asked routinely. All cases were reviewed and
      categorized in a multidisciplinary meeting. Any discrepancy between the clinical
      and post-mortem diagnosis was determined by a pathologist. RESULTS: The mortality
      rate of colon surgery was 8.0% (n = 71), 23% for emergency surgery and 6% for
      elective surgery (p < 0.001). For patients under 70 years of age the mortality
      rate was 4.3%, for patients over 70 years of age 11.2% (p < 0.001). Autopsy was
      performed in 62% (n = 44) of the patients. Discrepancy between clinical and post
      mortem findings was documented in 14%. CONCLUSION: Postoperative mortality after
      colon surgery is influenced by the timing of surgery (elective or emergency
      procedure) and the age of the patient. A discrepancy of 14% between clinical
      cause of death and post-mortem cause of death justifies the need for obtaining
      autopsy in this type of surgery.

PMID- 12806198
TI  - Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal
      carcinomas.
AB  - AIM: To determine whether superparamagnetic iron oxide-enhanced magnetic
      resonance imaging (SPIO-MRI) could replace intravenous contrast-enhanced spiral
      CT (iv-CT) and spiral CT during arterial portography (CTAP) combined with spiral
      CT hepatic angiography (CTHA) in the diagnosis of liver metastases from
      colorectal carcinomas. METHODS: Twenty-six adult patients with liver metastases
      were studied preoperatively by means of iv-CT, CTAP/CTHA, and SPIO-MRI.
      Preoperative diagnoses using iv-CT, CTAP/CTHA, and SPIO-MRI were compared with
      intraoperative and pathological findings in resected specimens. The gold standard
      for the lesions that were resected was histological examination. Intraoperative
      findings represented the gold standard for lesions that were not resected.
      RESULTS: Twenty-six patients were found to have a total number of 43 liver
      metastases. The sensitivities of iv-CT, CTAP/CTHA, and SPIO-MRI were 74.4, 100,
      and 90.7%, respectively. SPIO-MRI was significantly superior to iv-CT (p < 0.05).
      The positive predictive values of iv-CT, CTAP/CTHA, and SPIO-MRI were 97.0, 91.5,
      and 100%, respectively. CTAP/CTHA yielded four false-positive lesions. In
      contrast, we detected no false-positive findings using SPIO-MRI. CONCLUSIONS:
      These results suggest that SPIO-MRI might not completely replace CTAP/CTHA, but
      could replace iv-CT in the diagnosis of liver metastases from colorectal
      carcinomas. It is thought that SPIO-MRI is a promising imaging modality for
      diagnosing liver metastases in patients with colorectal carcinoma because of its
      relatively high sensitivity and extremely high specificity.

PMID- 12806199
TI  - Eosinophilic enteritis presenting as acute intestinal obstruction: a case report
      and review of the literature.
AB  - A 37-year-old man was admitted to our hospital complaining of severe abdominal
      pain and vomiting. His abdomen was distended, and there was diffuse tenderness
      and guarding in all four quadrants. Laboratory examinations revealed leukocytosis
      without eosinophilia. Abdominal radiograph revealed air-fluid levels in the small
      intestine. Computed tomography confirmed a dilatation of the small intestine and
      the presence of ascites. An emergency laparotomy was performed for a diagnosis of
      peritonitis due to intestinal obstruction. A large amount of yellow transudate
      was present in the abdominal cavity. An area of induration in the ileum was
      identified about 40 cm from the ileocecal valve. The ileum proximal to the
      induration was dilated, and the site of obstruction seemed to be the indurated
      segment. A partial iliectomy was performed. Histologically, dense infiltration of
      eosinophils was found transmurally, and eosinophilic enteritis was diagnosed. One
      year later, the patient was free of gastrointestinal symptoms. The relevant
      literature on eosinophilic gastroenteritis is discussed.

PMID- 12806200
TI  - Transhepatic placement of an enteral stent to treat jaundice in a tumor
      recurrence obstructed afferent loop after a whipple procedure.
AB  - Tumour recurrence that obstructs the afferent limb, blocking outflow of bile and
      pancreatic juice, constitutes a major clinical problem after a Whipple procedure.
      The endoscopic route is often not a possible alternative. Surgery may be
      difficult and perhaps dangerous to the often very sick patient and decompression
      with fine bore catheters may lead to cholangitis. External drainage is
      inconvenient to the patient. The present case describes a less invasive method to
      provide adequate drainage of the obstructed jejunal limb by insertion of a 22-mm
      enteral Wallstent transhepatically. The patient became and stayed anicteric
      during 7 months' follow-up.

PMID- 12806201
TI  - Bile duct cancer developing 21 years after choledochoduodenostomy.
AB  - BACKGROUND: Cholangiocarcinoma in patients with choledochoenterostomy has been a
      rare condition with few cases reported in the literature written in English, and
      there have been few pathological descriptions of this disease. However, it has
      recently been documented as a late complication of choledochoenteric anastomosis,
      and has become a serious issue today since choledochoenterostomy and
      sphincteroplasty for benign biliary lesions were frequently resorted to in the
      1970s and 1980s. The authors here present a case of a 67-year-old woman who
      developed a cholangiocarcinoma 21 years after choledochoduodenostomy. METHODS:
      The patient underwent a curative resection of the tumor with a
      hepatopancreatoduodenectomy after a detailed preoperative assessment, including
      cholangiography and cholangioscopy. RESULTS: Although this tumor has been
      reported to have a poor prognosis, a precise preoperative evaluation and
      aggressive surgery may contribute to better survival. Pathologically, the tumor
      originated in the bile duct mucosa of the choledochoduodenostomy, and was
      accompanied by intestinal and pyloric gland-like metaplasia. CONCLUSION: These
      epithelial changes presumably induced by chronic inflammation due to the reflux
      of intestinal contents and bile stasis may be responsible for the carcinogenesis.

PMID- 12806202
TI  - Pneumoperitoneum without perforation of the gastrointestinal tract.
AB  - Pneumoperitoneum (PP) is usually the result of perforation of the
      gastrointestinal (GI) tract with associated peritonitis. However, other rare
      causes, including spontaneous PP incidental to intrathoracic, intra-abdominal,
      gynecologic, and miscellaneous other origins not associated with a perforated GI
      tract have been described in the literature. Six cases of PP without any
      perforated GI tract are reported. Three patients with generalized peritonitis
      underwent exploratory laparotomy or laparoscopy when clinical examinations
      suggested an acute abdomen. At surgical procedure, perforated pyometra,
      perforated liver abscess and a ruptured necrotic lesion of a liver metastasis
      were documented in these patients, respectively. We also saw 3 PP patients not
      associated with peritonitis. Two patients with PP caused by pneumatosis cystoides
      intestinalis were encountered, 1 was managed conservatively and the other
      received diagnostic laparoscopy. A patient in whom pneumomediastinum and
      pneumoretroperitoneum were accompanied by PP caused by an alveolar rupture based
      on decreased pulmonary compliance due to malnutrition was managed conservatively.
      The history of the patient and knowledge of the less frequent causes of PP can
      possibly contribute towards refraining from exploratory laparotomy in the absence
      of peritonitis.

PMID- 12806203
TI  - In vivo studies of the genetically modified mouse kidney.
AB  - Gene-targeted mice provide a powerful approach to study the physiological and
      pathophysiological role of a given protein in kidney function and can give
      insights on the functional importance of these proteins under in vivo conditions
      as well as on the potential compensating mechanisms in their absence. Full
      utilisation of these animal models requires adaptation of the respective methods
      to the size of the mouse. This applies especially to in vivo studies in mice
      which have to deal with rather small structures and volumes, e.g. vessels for
      cannulation, plasma volumes or urinary flow rates. Here some aspects which can
      help to study kidney function in the mouse in vivo are outlined. The
      applicability of these in vivo methods are stressed by reviewing their very
      recent application in mice being deficient for either ROMK or SGK1.

PMID- 12806204
TI  - Effect of tetrahydrobiopterin on blood pressure in rats after subtotal
      nephrectomy.
AB  - BACKGROUND: Previous studies have shown that endothelial dysfunction after 5/6
      nephrectomy (5/6 Nx) in rats is associated with decreased nitric oxide (NO)
      bioavailability and increased vascular superoxide production. Blood pressure is
      significantly increased by day 10 after surgery. Tetrahydrobiopterin (BH4) is a
      key cofactor of NO synthase. Suboptimal levels of BH4 result in uncoupling of NO
      synthase, low NO synthesis and augmented production of superoxide anions. The aim
      of this study was to evaluate whether BH4 supplementation may improve NO
      production and prevent the increase of blood pressure after 5/6 Nx. METHODS:
      Three groups were evaluated: 5/6 Nx (untreated rats), BH4 (5/6 Nx rats treated
      with BH4, 10 mg/day i.p. for 10 days) and L-ARG (5/6 Nx rats treated with L
      arginine, 260 mg/kg BW, p.o for 10 days). Systolic blood pressure (SBP), urinary
      nitrate excretion (UNO(3)) and creatinine clearance (CCR) were measured before
      surgery and on days 3 and 10 after surgery. Endothelial NO synthase (eNOS)
      protein content of mesenteric resistance vessels was measured at the end of the
      study. RESULTS: SBP increased from 107 +/- 2 to 127 +/- 4 mm Hg in untreated 5/6
      Nx rats (p < 0.01). By contrast, rats treated with BH4 or L-ARG remained
      normotensive. Ten days after 5/6 Nx, creatinine clearance decreased similarly in
      all groups. Both BH4 and L-ARG supplementation markedly increased UNO(3)
      excretion. The mesenteric vascular expression of eNOs protein was significantly
      higher in BH4 but not in L-ARG, compared with Nx rats. CONCLUSIONS: BH4
      supplementation prevents the earlier increase in blood pressure observed in rats
      after 5/6 Nx, possibly by upregulating eNOS in resistance vessels.

PMID- 12806205
TI  - Identification of a new member of type I Na/phosphate co-transporter in the rat
      kidney.
AB  - AIM: To clone new phosphate transporters from the kidney. METHODS: EST bank was
      screened for new members of Na-dependent inorganic phosphate (P(i)) co
      transporter. To obtain a full-length clone, a rat kidney cDNA library was
      screened with the EST clone as a probe. RESULTS: We isolated a cDNA that encodes
      a type I Na/P(i) co-transporter. Based on the sequence homology and tissue
      distribution, it will be the rat ortholog of human NPT4 (Solute Carrier family
      17, member A3, SLC17A3) and is designated rNPT4. When expressed in Xenopus
      oocytes, Na/P(i) co-transport activity was demonstrated. In Northern blotting
      analysis, rNPT4 was selectively expressed in the liver and kidney. In
      immunohistochemical analysis, rNPT4 was localized at the apical membrane of the
      proximal tubules (S2, S3) in the rat kidney. The electron microscopic studies
      confirmed this finding. CONCLUSION: The present study revealed the expression of
      a new type I Na/P(i) co-transporter at the brush border membrane of the proximal
      tubules in the kidney.

PMID- 12806206
TI  - Orexin: a link between energy homeostasis and adaptive behaviour.
AB  - PURPOSE OF REVIEW: Orexins, also called hypocretins, are a pair of neuropeptides
      expressed by a specific population of neurons in the lateral hypothalamic area, a
      region of the brain implicated in feeding, arousal and motivated behaviour. The
      purpose of this review is to summarize recent relevant findings on orexins, and
      discuss the physiological roles of these peptides. RECENT FINDINGS: Recent
      findings suggest that orexin neurons provide a critical link between the
      peripheral energy balance and central nervous system mechanisms that coordinate
      sleep-wakefulness and motivated behaviours such as food seeking, especially in
      the physiological state of fasting stress. SUMMARY: Orexin (hypocretin) neurons
      interact with feeding centres in the hypothalamus, arousal and sleep-wakefulness
      centres in the brainstem, sympathetic and parasympathetic nuclei and the limbic
      system. The central administration of orexin dose-dependently increases food
      intake, waking time, motor activity, and metabolic rate, as well as heart rate
      and blood pressure in many species. Recent electrophysiological studies have
      shown that orexin neurons are regulated by metabolic cues, including leptin,
      glucose, and ghrelin, as well as monoamines and acetylcholin. Orexin neurons thus
      have the requisite functional interactions with hypothalamic feeding pathways and
      monoaminergic-cholinergic centres in the brain stem, and regulation by
      nutritional factors, to suggest that they may be an important cellular link in
      the integration of adaptive behaviour associated with arousal and energy
      homeostasis.

PMID- 12806207
TI  - Central regulators of food intake.
AB  - PURPOSE OF REVIEW: Obesity is a major public health problem and is associated
      with significant morbidity and mortality from coronary heart disease and type 2
      diabetes. The population is becoming increasingly obese, yet for individuals
      weight is regulated within a narrow range. This regulation depends on the balance
      between energy intake (in the form of food) and energy expenditure. Thus in order
      to regulate weight and energy stores, the body must be able to control food
      intake accurately. Recently there has been a remarkable increase in our
      understanding of the molecular mechanisms regulating food intake and energy
      homeostasis. RECENT FINDINGS: There is increased understanding of the central
      pathways by which known neurotransmitters affect food intake. These include
      peptides expressed in hypothalamic nuclei, but other brain regions including
      brain stem, amygdala and nucleus accumbens, are also important. Further central
      transmitters have been identified, such as that encoded by the gene identified in
      mice with the mahoganoid mutation, and roles for known transmitters have been
      elucidated, such as endocannabinoids and acetylcholine. There is new evidence
      regarding peripheral modulation of these pathways including the role of ghrelin
      as an initiator of feeding, and peptide YY as a medium-term satiety signal.
      SUMMARY: Complex central circuitry controls food intake and energy expenditure.
      Circulating factors that modulate these pathways have appetite stimulation or
      satiety effects. These are potentially important targets for therapy in obesity.
      Single-gene models of obesity in animals are important in understanding these
      pathways, however human clinical correlates for genetically determined obesity
      are uncommon.

PMID- 12806208
TI  - Emerging trends in the search for genetic variants predisposing to human obesity.
AB  - PURPOSE OF REVIEW: The models currently proposed for the genetic architecture of
      obesity are critically reviewed in the light of recent developments in the search
      for genetic causes of this condition. RECENT FINDINGS: As for many other
      'complex' diseases, most of the genetic variants predisposing to human obesity
      have not yet been identified. To date, investigation of the genetic contribution
      to obesity has been conducted according to two main hypotheses. The common
      disease/common variant hypothesis proposes that the genetic architecture of
      complex diseases (including obesity) is likely to consist of a limited number of
      alleles, each conferring a small increase in risk to the individual.
      Alternatively, it has also been proposed that complex diseases such as obesity
      may instead result from the effects of a large number of rare variants, with
      substantial allelic heterogeneity at disease-causing loci. These two hypotheses
      have shaped strategies for the identification of disease genes, including the use
      of linkage analysis, association studies and the systematic sequencing of
      candidate genes. Linkage studies have recently been very successful in
      identifying new genes in which mutations cause rare monogenic syndromes of
      obesity. In common obesity, numerous linkage and association studies have
      suggested that an increasing number of genetic loci could be involved. Overall,
      however, these studies have failed to identify the causal genetic variants. In
      contrast, the direct sequencing of well-chosen candidate genes has led to the
      identification of numerous rare alleles causing both syndromic and common
      obesity, which are less severe forms of the condition in humans. SUMMARY: The
      genetic architecture of obesity is still a matter of debate. The previously
      accepted hypothesis of a small number of common variants has been undermined by
      the low reproducibility of association studies and inconsistencies among genome
      scans for obesity. While high-throughput association mapping of candidate regions
      holds some promise for the identification of common susceptibility alleles, it
      must also be considered that the genetic predisposition to obesity may instead
      result from multiple rare variants in a large number of genes.

PMID- 12806209
TI  - Effect of thyroid hormone on gene expression.
AB  - PURPOSE OF REVIEW: Thyroid hormones are key regulators of development and
      metabolism that modulate transcription via nuclear receptors. Although the
      molecular actions of thyroid hormones have been thoroughly studied, their
      pleiotropic effects are mediated by complex changes in expression of numerous,
      but still largely unknown, target genes. This review summarizes the recent
      advances in the characterization of target genes in different organs. RECENT
      FINDINGS: New patterns of gene expression regulation have been described in
      tissues with known physiological actions of thyroid hormone, that is brain,
      liver, skeletal and cardiac muscles, and brown and white adipose tissues. The
      studies have benefited from the numerous transgenic models with altered thyroid
      hormone receptor expression and the application of DNA microarray technology to
      mouse and human tissues. SUMMARY: Data on thyroid hormone-mediated control of
      gene expression and on the roles of the different thyroid hormone receptor
      isoforms bring new clues to our understanding of the molecular mechanisms of
      thyroid hormone action in physiological situations and, most importantly, in
      diseases associated with alterations of the thyroid status.

PMID- 12806210
TI  - Cytokines: the mother of catabolic mediators!

PMID- 12806211
TI  - Body composition measurements: interpretation finally made easy for clinical use.
AB  - PURPOSE OF REVIEW: This review presents the latest clinical applications of
      bioelectrical impedance analysis. It discusses the evaluation of nutritional
      status by using fat-free mass and body fat, percentiles of fat-free mass and body
      fat, height-normalized fat-free mass and body fat mass indices and a
      resistance/reactance vector graph. RECENT FINDINGS: Fat-free mass and body fat
      can be used to evaluate nutritional status by comparing individuals or groups of
      individuals with themselves or with reference values. Percentile distributions
      are also useful in determining whether individuals or groups fall within the
      population range. Percentile ranks can also be used to define nutritional
      depletion and obesity. The use of the fat-free mass and body fat mass indices has
      the advantage of compensating for differences in body height. The use of low,
      normal, high and very high fat-free mass and body fat mass indices ranges that
      correspond to underweight, normal, overweight and obese body mass index
      categories further aid in the nutritional assessment process. With vector
      bioelectrical impedance analysis, an individual impedance vector is compared with
      the 50, 75, and 95% tolerance ellipses calculated in the reference, healthy
      population, allowing evaluation in any clinical condition. More accurate
      estimates of conventional bioelectrical impedance analysis equations might be
      obtained in individuals with a normal impedance vector. SUMMARY: The assessment
      of fat-free mass and body fat provides valuable information about changes in body
      composition with weight gain or loss and physical activity, and during ageing.
      The use of percentiles and height-normalized fat-free mass and body fat permit
      the classification of patients as under or overnourished.

PMID- 12806212
TI  - Cachexia and obesity: two sides of one coin?
AB  - PURPOSE OF REVIEW: Leptin, a member of the interleukin-6 superfamily of proteins,
      modifies the gene expression and synthetic pathway of both orexigenic (appetite
      stimulating) and anorexigenic (appetite-suppressing) molecules in the
      hypothalamus, thereby controlling adipocyte energy stores. Lack of leptin
      secretion or the inability of leptin to interact with these molecules via leptin
      receptors, prevent leptin's effects and lead to obesity. It is not well known,
      however, how these feeding-regulatory molecules are affected in cachexia
      associated with cancer and other critical conditions in which cytokines such as
      interleukin-1 and interleukin-6 may have a key role. RECENT FINDINGS: Decreased
      leptin and increased leptin-like signaling by cytokines in the hypothalamus are
      the hallmark of obesity and cachexia, respectively. Increased orexigenic and
      impaired anorexigenic signaling produces hyperphagia and obesity, while the
      reverse applies to anorexia-cachexia in which adaptive feeding response to
      starvation is lacking or insufficient. SUMMARY: Imbalanced operation of
      orexigenic and anorexigenic circuits perturbs the homeostatic loop of body weight
      regulation leading to either obesity or cachexia. Modifiers of the central
      effects on appetite and energy metabolism could restore the balance and be
      effective for treating both conditions. In cachexia this may especially be true
      when combined with agents that target muscle and protein breakdown.

PMID- 12806213
TI  - Cytokines in the pathogenesis of cancer cachexia.
AB  - PURPOSE OF REVIEW: The aim of the present review is to summarize and update the
      role of different cytokines in the pathogenesis of cancer cachexia and to provide
      therapeutic strategies based on cytokine action. RECENT FINDINGS: Cancer cachexia
      is a syndrome characterized by a marked weight loss, anorexia, asthenia and
      anemia. The cachectic state is invariably associated with the presence and growth
      of the tumor and leads to a malnutrition status due to the induction of anorexia
      or decreased food intake. In addition, the competition for nutrients between the
      tumor and the host leads to an accelerated starvation state which promotes severe
      metabolic disturbances in the host, including hypermetabolism, which leads to an
      increased energetic inefficiency. Different cytokines are clearly implicated in
      this process, possibly being responsible for anorexia, hypermetabolism and many
      other metabolic abnormalities, such as muscle proteolysis and apoptosis. SUMMARY:
      Although the search for the cachectic factor(s) started a long time ago, and
      although many scientific and economic efforts have been devoted to its discovery,
      we are still a long way from knowing the whole truth. A lot of progress has been
      made, however, in understanding the role of different cytokines - tumor necrosis
      factor and IL-6 in particular - in muscle wasting associated with cancer
      cachexia, perhaps the most paradigmatic feature of this complex syndrome.

PMID- 12806214
TI  - Mechanisms of skeletal muscle depletion in wasting syndromes: role of ATP
      ubiquitin-dependent proteolysis.
AB  - PURPOSE OF REVIEW: Muscle protein wasting frequently complicates patient outcome
      in several chronic pathologies. The underlying mechanisms remain largely obscure,
      although studies on experimental models have clarified that a complex interplay
      of different factors such as nutrient supply, classical hormones, cytokines and
      other less well defined factors likely concur in causing muscle depletion. The
      aim of the present review is to highlight some crucial points in the
      interpretation of the data available about the contribution of the different
      proteolytic systems, with particular reference to the ubiquitin-proteasome
      system, in the onset of muscle protein wasting in disease states. RECENT
      FINDINGS: Much effort has been directed to understanding the role of different
      signals, transduction pathways, and proteolytic mechanisms in the acceleration of
      muscle protein catabolism. Several reports propose that ATP-ubiquitin-dependent
      proteolysis plays a critical role in the enhancement of muscle protein catabolism
      observed in different pathological states. Other papers, however, suggest that
      the lysosomal or the calcium-dependent proteolytic pathways or both may be
      involved. Finally, the studies have been extended to evaluate the possibility of
      interfering pharmacologically with the onset of muscle protein hypercatabolism.
      SUMMARY: As the present overview points out, several questions still remain
      unanswered in the issue of muscle wasting. While many different signals that have
      the potential to enforce the acceleration of muscle protein breakdown have been
      identified, it is largely unknown how they are transduced and converge into the
      hypercatabolic response and how the proteolytic pathways involved are activated.
      The concept seems to emerge that there may be a coordinated action of different
      proteolytic pathways in setting up muscle protein turnover towards excess
      catabolism.

PMID- 12806216
TI  - Improving food intake in anorectic cancer patients.
AB  - PURPOSE OF REVIEW: Anorexia and reduced food intake are important issues in the
      management of cancer patients. This article discusses the currently proposed
      hypothesis of its pathogenesis, and reviews the available and future therapeutic
      options as they relate to the pathogenic mechanisms. RECENT FINDINGS: Currently
      available data suggest that the pathogenesis of cancer anorexia is
      multifactorial, and involves most of the hypothalamic neuronal signaling pathways
      modulating energy intake. Thus, a number of factors have been proposed as
      putative mediators of cancer anorexia, including hormones (e.g. leptin),
      neuropeptides (e.g. neuropeptide Y), cytokines (e.g. IL-1, IL-6, tumor necrosis
      factor) and neurotransmitters (e.g. serotonin and dopamine). It is unlikely,
      however, that they represent separate and distinct pathogenic mechanisms, rather
      it appears that close interrelationships may exist among them. In line with this
      reasoning, consistent experimental and human data suggest that hypothalamic
      monoaminergic neurotransmission may represent a major target on which different
      anorexia-related factors converge. SUMMARY: In the pathogenesis of cancer
      anorexia, cytokines appear to play a key role. Their increased expression during
      tumor growth inhibits the hypothalamus to appropriately respond to peripheral
      signals, by persistently activating the melanocortin system and inhibiting the
      neuropeptide Y neuronal pathway. Hypothalamic monoaminergic neurotransmission may
      significantly contribute to these effects. Thus, interfering pharmacologically
      with cytokine expression or hypothalamic monoaminergic neurotransmissions is an
      effective therapeutic strategy in anorectic cancer patients.

PMID- 12806215
TI  - Metabolic alterations during inflammation and its modulation by central actions
      of omega-3 fatty acids.
AB  - PURPOSE OF REVIEW: To discuss the possible relationship between long-chain
      polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin,
      various neurotransmitters in the brain, and their role in anorexia of acute and
      chronic inflammatory conditions and cancer. RECENT FINDINGS: Recent studies have
      shown that long-chain polyunsaturated fatty acids, especially the omega-3 series,
      have antiinflammatory actions, increase the concentrations of anandamides,
      enhance the levels of acetylcholine and nitric oxide and modulate the
      concentrations and actions of various neurotransmitters, including leptin, in the
      brain. Patients suffering from acute and chronic inflammatory conditions have low
      tissue concentrations of various long-chain polyunsaturated fatty acids, and high
      levels of proinflammatory cytokines that can cause anorexia and decrease food
      intake. SUMMARY: It is suggested that supplementation of long-chain
      polyunsaturated fatty acids may have a role in the prevention and treatment of
      acute and chronic inflammatory conditions, improving anorexia associated with
      these conditions.

PMID- 12806217
TI  - Nutritional aspects in ultra-endurance exercise.
AB  - PURPOSE OF REVIEW: Despite much current debate regarding central and peripheral
      neural mechanisms which may be responsible for the onset of fatigue during
      prolonged exercise, maintenance of nutritional and hydration status remains
      critical for successful participation in ultra-endurance exercise. This review
      focuses on substrate and fluid homeostasis during ultra-endurance exercise and
      the use of nutritional supplementation both as ergogenic aid and to attenuate
      exercise-induced immunosuppression. RECENT FINDINGS: Current evidence continues
      to support mandatory high carbohydrate intakes (1). before the event to maximize
      muscle glycogen stores, (2). during the event to prevent hypoglycaemia and (3).
      after the event to optimize post-event repletion of endogenous carbohydrate
      stores. No consistent performance benefit has yet been shown following a high-fat
      diet. Greater utilization of intrafascicular triglyceride stores appears to
      account for additional fat utilization in females. Recent trends towards
      excessive fluid intake have resulted in frequent reports of hyponatraemic
      hyperhydration in ultra-distance athletes, with greater incidence in women than
      in men. Carbohydrate supplementation during the event attenuates
      immunosuppressive hormonal and cytokine responses to ultra-endurance exercise,
      but may impair vitamin C absorption, while the ergogenic value of caffeine
      supplementation in ultra-endurance performance is currently being questioned.
      SUMMARY: Meeting macronutrient and fluid intake demands remains an important
      priority for ultra-endurance athletes. Yet these athletes are reported to present
      with a high incidence of disordered eating patterns during periods of training,
      and excessive fluid replacement strategies have resulted in an increased
      incidence of water intoxication with resultant central nervous system
      dysfunction.

PMID- 12806218
TI  - Muscular dystrophies: influence of physical conditioning on the disease
      evolution.
AB  - PURPOSE OF REVIEW: To summarize the current knowledge of the effects of physical
      activity on muscular dystrophies. RECENT FINDINGS: Although the usefulness of
      exercise training in muscular dystrophy patients has been debated for many years,
      only a limited number of articles addressing this issue have been published to
      date. Existing studies on the effects of strength training in patients with
      muscular dystrophies have shown promising results, but interpretations are
      hampered by several methodological shortcomings. SUMMARY: The scientific basis
      for solid recommendations of different exercise regimens in muscular dystrophies
      is poor, but existing data suggest beneficial effects of adopting an active
      lifestyle. Low- to moderate-intensity resistance and aerobic training may be
      recommended in slowly progressive myopathic disorders. To date, there is no
      evidence to support the recommendation of high-resistance exercise regimens over
      low-moderate intensity exercise. In rapidly progressive myopathies, which are due
      to aberrant structural proteins such as Duchenne muscular dystrophy, the use of
      high-resistance and eccentric training should be avoided. There is still,
      however, no evidence that physical training can influence the evolution of
      muscular dystrophies in the long term.

PMID- 12806219
TI  - Effects of fructose on hepatic glucose metabolism.
AB  - PURPOSE OF REVIEW: The liver plays an important role in glucose tolerance. A
      number of studies have suggested fructose improves glucose tolerance especially
      in insulin resistant settings. This review summarizes the recent work suggesting
      that fructose enhances glucose tolerance by augmenting liver glucose uptake. This
      increase may be mediated by the translocation and activation of hepatic
      glucokinase. RECENT FINDINGS: Catalytic quantities of fructose (<10% of total
      carbohydrate flux) enhance liver glucose uptake in a dose dependent manner. The
      primary fate of the glucose is glycogen synthesis. The ability of fructose to
      augment liver glucose uptake is not impaired by the presence of marked insulin
      resistance such as in type 2 diabetes or infection. In addition, it is able to
      further enhance liver glucose uptake in the normal adapted setting of total
      parenteral nutrition and reverse the infected-induced decrease in liver glucose
      uptake. Studies also demonstrate that the beneficial effects of fructose on liver
      glucose uptake during chronic nutritional support do not persist. SUMMARY:
      Fructose is a potent acute regulator of liver glucose uptake and glycogen
      synthesis. Inclusion of catalytic quantities of fructose in a carbohydrate meal
      improves glucose tolerance. This improvement is primarily mediated by the
      activation of hepatic glucokinase and consequent facilitation of liver glucose
      uptake. The improvement in glucose tolerance is most evident in insulin resistant
      settings (e.g. Type 2 diabetes and infection). The beneficial effect of fructose
      on hepatic glucose disposal, however, does not persist if fructose is given
      continuously such as in total parenteral nutrition.

PMID- 12806220
TI  - Role of the liver in the control of glucose-lipid utilization and body weight.
AB  - PURPOSE OF REVIEW: This review depicts recent developments concerning the role of
      the liver in control of carbohydrate and lipid utilization from ingestion to
      storage; it covers the liver's influence on food intake, post-absorptive nutrient
      metabolism and body weight. The mechanisms involved have implications for the
      pathogenesis of obesity and type II diabetes. RECENT FINDINGS: Recent studies
      have identified some of the molecular and biochemical mechanisms which control
      whole body and hepatic carbohydrate and lipid metabolism, thus providing the
      basis of the liver's role in the control of food intake, metabolism, and body
      weight. Fatty acids are known to effect gene transcription in various ways.
      Advances in our understanding of the control of glucose and lipid utilization by
      the liver include (1). a better functional characterization of some newly
      discovered transcription factors, (2). new discoveries concerning the
      physiological and pathophysiological role of hepatic glucokinase and of the
      glycogen-targeting subunits of protein phosphatase-1, and (3). the demonstration
      of substantial overlap in the molecular control mechanisms of glucose-lipid
      utilization. Also, impaired insulin signaling due to a certain gene (Foxo1) has
      emerged as a possible unifying mechanism for various common metabolic
      abnormalities of type II diabetes. Finally, recent findings confirm and extend
      previous knowledge about the important role of hepatic nerves in the control of
      liver and whole body glucose-lipid utilization. SUMMARY: The identification of
      new molecular and neural mechanisms of the hepatic control of glucose-lipid
      utilization and body weight provides a focus for future studies and may
      eventually help to develop new treatments for obesity and type II diabetes.

PMID- 12806221
TI  - Post-liver transplant obesity and diabetes.
AB  - PURPOSE OF REVIEW: Post-liver transplant patients present a vast array of
      metabolic changes in the early and late phase which impact on their morbidity and
      mortality. The development of obesity and diabetes in these patients has been
      widely described in the literature with several hypotheses suggested: liver
      donor, nutritional and metabolic state, and immunosuppressive drugs. RECENT
      FINDINGS: Most that is known about the development of these metabolic
      derangements has been attributed to the drugs used, especially the
      corticosteroids. When these have been used in higher doses for longer periods to
      treat rejection, the incidence of diabetes and obesity seems to be higher.
      However cyclosporine and to a lesser extent tacrolimus are also related to these
      alterations. SUMMARY: As long-term survival improves in liver transplant
      patients, cardiovascular complications associated with dyslipidemia, obesity, and
      diabetes are emerging as risk factors for late morbidity and mortality.
      Therefore, it is important to assess the potential risk factors related to these
      complications, in order to prevent or decrease their incidence. From what has
      been seen, immunossupressive drugs seem to be the greatest risk factor for the
      development of metabolic derangements in post-transplantation patients. However
      other risk factors might also be involved, such as non-healthy eating habits and
      lack of exercise. The latter can be preventable if counseling policies are
      targeted at these patients in the pre-transplantation phase and continued after
      the operation.

PMID- 12806222
TI  - Enteroinsular signaling: perspectives on the role of the gastrointestinal
      hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide
      in normal and abnormal glucose metabolism.
AB  - PURPOSE OF REVIEW: The gastrointestinal hormones glucagon-like peptide 1 and
      glucose-dependent insulinotropic polypeptide are emerging as essential regulators
      of insulin secretion and glucose homeostasis. These peptides, termed incretins,
      are the key intermediaries in a system that links the absorption of nutrients in
      the gut with important metabolic processes in substrate assimilation. New
      findings indicate that the enteroinsular system mediated by the incretins is
      relevant to both the pathophysiology and treatment of diabetes. RECENT FINDINGS:
      Important advances have been made in the understanding of mechanisms fundamental
      to incretin function such as their release from the intestine during meals, their
      actions on beta-cell secretion, and extrapancreatic effects. In addition, the
      regulation of islet growth by glucagon-like peptide 1 and glucose-dependent
      insulinotropic polypeptide is a novel area with considerable support from recent
      studies. Abnormalities of incretin function are present in patients with diabetes
      and current research has implicated specific defects of both glucagon-like
      peptide 1 and glucose-dependent insulinotropic polypeptide action in diabetes.
      Finally, several pharmacological applications of the incretin signaling pathways
      are under active investigation for the treatment of diabetes. SUMMARY: With the
      intensified research of the last several years the physiologic importance of the
      incretins has been clarified. Enteroinsular signaling is an essential component
      of the metabolic processes that govern carbohydrate, and likely other nutrient
      metabolism. As a pathophysiology of the incretins emerges, glucagon-like peptide
      1 and glucose-dependent insulinotropic polypeptide will have increasing clinical
      relevance. This is currently exemplified by the development of therapeutics for
      diabetes that work through the incretin signaling pathways.

PMID- 12806223
TI  - Cold-induced metabolism.
AB  - PURPOSE OF REVIEW: Cold response can be insulative (drop in peripheral
      temperature) or metabolic (increase in energy expenditure). Nonshivering
      thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat
      production in brown adipose tissue is a well known component of this metabolic
      response in infants and several animal species. In adult humans, however, its
      role is less clear. Here we explore recent findings on the role and variability
      of nonshivering thermogenesis in adults. RECENT FINDINGS: Large individual
      differences exist in mild cold response with respect to the relative contribution
      of the insulative response and the metabolic (nonshivering) response. In search
      for the possible explanations of this variation, recent studies on potential
      mechanisms of nonshivering thermogenesis in humans are presented. Emphasis is
      given to the role of uncoupling proteins, mitochondrial ATP-synthase, and calcium
      cycling. The potential contribution of human skeletal muscle to nonshivering
      thermogenesis is discussed. The differences in nonshivering thermogenesis can
      partly be attributed to factors such as age, gender, physical fitness,
      adaptation, and diet. There are indications that genetic variation affect cold
      response. SUMMARY: The implications of the observed large individual variation in
      cold response is that a low metabolic response to cold can partly explain
      increased risk to develop obesity. Both the effect of environmental factors and
      genetic factors on nonshivering thermogenesis require more well controlled
      studies. With extended knowledge on these factors it can be ascertained if a
      pharmacological regimen is possible which would mimic the effects of chronic cold
      or elevated catecholamine levels, without attendant side effects.

PMID- 12806225
TI  - Temper tantrums in young children: 1. Behavioral composition.
AB  - Although tantrums are among the most common behavioral problems of young children
      and may predict future antisocial behavior, little is known about them. To
      develop a model of this important phenomenon of early childhood, behaviors
      reported in parental narratives of the tantrums of 335 children aged 18 to 60
      months were encoded as present or absent in consecutive 30-second periods.
      Principal Component (PC) analysis identified Anger and Distress as major,
      independent emotional and behavioral tantrum constituents. Anger-related
      behaviors formed PCs at three levels of intensity. High-intensity anger decreased
      with age, and low-intensity anger increased. Distress, the fourth PC, consisted
      of whining, crying, and comfort-seeking. Coping Style, the fifth PC, had high but
      opposite loadings on dropping down and running away, possibly reflecting the
      tendency to either "submit" or "escape." Model validity was indicated by
      significant correlations of the PCs with tantrum variables that were, by design,
      not included in the PC analysis.

PMID- 12806226
TI  - Temper tantrums in young children: 2. Tantrum duration and temporal organization.
AB  - This article completes the analysis of parental narratives of tantrums had by 335
      children aged 18 to 60 months. Modal tantrum durations were 0.5 to 1 minute; 75%
      of the tantrums lasted 5 minutes or less. If the child stamped or dropped to the
      floor in the first 30 seconds, the tantrum was likely to be shorter and the
      likelihood of parental intervention less. A novel analysis of behavior
      probabilities that permitted grouping of tantrums of different durations
      converged with our previous statistically independent results to yield a model of
      tantrums as the expression of two independent but partially overlapping emotional
      and behavioral processes: Anger and Distress. Anger rises quickly, has its peak
      at or near the beginning of the tantrum, and declines thereafter. Crying and
      comfort-seeking, components of Distress, slowly increase in probability across
      the tantrum. This model indicates that tantrums can provide a window on the
      intense emotional processes of childhood.

PMID- 12806227
TI  - Parental perceptions and satisfaction with stimulant medication for attention
      deficit hyperactivity disorder.
AB  - Few reports have documented parental perceptions of stimulants for attention
      deficit hyperactivity disorder (ADHD), despite the recent increased use of
      stimulants among youths. Of 302 parents recruited from six pediatric primary care
      clinics, 84% completed a survey of their knowledge, attitudes, and satisfaction
      with the medication their child was taking for ADHD. Two thirds of the parents
      believed that sugar and diet affect hyperactivity. Although few parents believed
      that stimulants could lead to drug abuse, 55% initially were hesitant to use
      medication on the basis of information in the lay press, and 38% believed that
      too many children receive medication for ADHD. Parents were more satisfied with
      the behavioral and academic improvement relative to improvement in their child's
      self-esteem. Attitudes were positively correlated with satisfaction and were more
      positive among white than nonwhite parents. The findings highlight parental
      misconceptions and reservations about ADHD medication treatment that require
      clarification as to whether race/ethnicity, income, and social status influence
      their views and use of treatments.

PMID- 12806228
TI  - Somatic growth of preterm infants during skin-to-skin care versus traditional
      holding: a randomized, controlled trial.
AB  - We performed this randomized trial to determine whether infants receiving skin-to
      skin care (SSC) grew more rapidly and had a shorter duration of hospital stay
      compared with infants held by their parents in a traditional way. Infants who met
      eligibility criteria (<or=32 wk of gestation, <or=1500 g, minimal ventilatory
      support, and hemodynamically stable) were randomized to traditional holding (TH)
      or SSC groups. Parents in both groups were allowed to hold infants for a total of
      8 hours per day (periods of up to 4 hr, twice/d). During the study, infants in
      the TH group were held 4.8 +/- 3.5 times per week and 76 +/- 39 minutes per day,
      and infants in the SSC group were held 4.0 +/- 2.8 times per week and 79 +/- 40
      minutes per day. No significant differences were observed in weight accretion or
      linear growth. However, exposure to SSC was associated with greater head growth,
      even after controlling for head circumference at birth (p =.03). SSC may increase
      the likelihood of successful breastfeeding.

PMID- 12806230
TI  - Developmental and behavioral pediatric practice patterns and implications for the
      workforce: results of the Future of Pediatric Education II Survey of Sections
      Project.
AB  - A survey of developmental-behavioral pediatricians was conducted to obtain data
      and insights on their current practice. As part of the Future of Pediatric
      Education (FOPE) II Survey of Sections Project, questionnaires were sent to
      individuals who were most likely to represent those pediatricians engaged in the
      subspecialty of developmental-behavioral pediatrics. Four groups of physicians
      were compared within the survey: developmental-behavioral fellowship group (n =
      272), developmental disabilities fellowship group (n = 139), general academic
      pediatrics or other fellowship group (n = 57), and a nonfellowship group (n =
      224). A majority of respondents indicated a need for an increased number of
      subspecialists in developmental-behavioral pediatrics in their community during
      the next 3 to 5 years. There were significant differences in the survey results
      of a variety of practice issues between those who had and had not received formal
      fellowship training. The survey data illustrate a developmental-behavioral
      pediatrician workforce that is becoming increasingly fellowship trained,
      receiving more referrals, and encountering constraints to seeing more patients in
      an era of declining reimbursement for services. To overcome these obstacles,
      stakeholders in child health, including health care payers, will need to be
      educated about the unique skills and clinical expertise of physicians in
      developmental-behavioral pediatrics and neurodevelopmental disabilities.

PMID- 12806229
TI  - Visual-spatial skills in children after open-heart surgery.
AB  - This study was part of a randomized clinical trial comparing the central nervous
      system effects of the two vital organ-support methods used in infant cardiac
      surgery: total circulatory arrest and low-flow cardiopulmonary bypass. The extent
      to which visual-spatial deficits are (1). associated with surgical and
      perioperative variables, (2). attributable to visual-perceptual, motor control,
      or metacognitive deficits, and (3). associated with adaptive difficulties at home
      or school was evaluated. The subjects were 155 8-year-old children with D
      transposition of the great arteries who underwent the arterial switch operation
      before 3 months of age. As part of a comprehensive evaluation, the Rey-Osterrieth
      Complex Figure (ROCF) was administered. ROCF copy productions were classified as
      having a Basal Organization Level of 1 (low) or 2 or greater. A five-category
      clinical rating was also assigned. More than half of the children in the cohort
      (52%) had copy productions scored at Level 1, more than twice the expected
      frequency. The risk of having a low score was not associated with vital organ
      support method or other surgical variables. On the basis of comparisons of the
      relative fits of nested logistic regression models, poor visual-perceptual
      abilities were more predictive of having a Level 1 score than either motor
      control or metacognitive deficits. Children with poor copy production scores had
      lower mathematics scores, but not lower reading scores or poorer parent and
      teacher ratings of adaptive competence. The percentage of children receiving
      remedial school services was associated with ROCF clinical rating, ranging from
      58% in the worst category to 8% in the best category. Visual-spatial deficits are
      common among children after infant heart surgery and seem to reflect visual
      perceptual rather than motor control or metacognitive deficits. In addition,
      these deficits do not seem to be clearly associated with the intraoperative
      methods or postoperative events evaluated.

PMID- 12806231
TI  - Stability and predictors of health-related quality of life of inner-city girls.
AB  - Predictors of health-related quality of life (HR-QOL) among inner-city girls and
      its effect on health care use were evaluated. Adolescent girls aged 14 to 18
      years (n = 127) completed a demographic and risk-behavior interview, the Kaufman
      Brief Intellectual Test, and the Medical Outcomes Study Short Form-36. Medical
      charts were reviewed for health care use. Two assessments were completed 6 months
      apart. Participants reported stable and poor HR-QOL compared with norms for
      similar aged females. HR-QOL was associated with some concurrent risk taking.
      Lower self-perceptions of mental health were associated with inconsistent condom
      use, smoking, and alcohol use; lower self-perceptions of physical health were
      associated with pregnancy and smoking. Predictive associations were not found.
      There was a trend for poorer physical health to be associated with more clinic
      visits. This study highlights the need for research aimed at both improving self
      perceptions of health and decreasing high-risk behavior among inner-city girls.

PMID- 12806232
TI  - Benefits of a doula present at the birth of a child.

PMID- 12806233
TI  - Assessment of attachment security in a clinical setting: observations of parents
      and children.

PMID- 12806234
TI  - History of developmental-behavioral pediatrics.

PMID- 12806235
TI  - Pleural diseases.

PMID- 12806236
TI  - Eosinophilic pleural effusions.
AB  - Eosinophilic pleural effusions, defined as a pleural effusion that contains at
      least 10% eosinophils, may be caused by almost every condition that can cause
      pleural disease. Eosinophilic pleural effusion occurs most commonly during
      conditions associated with the presence of blood or air in the pleural space,
      infections, and malignancy. Drug-induced pleural effusions, pleural effusions
      accompanying pulmonary embolism, and benign asbestos pleural effusions are also
      among the common causes of eosinophilic pleural effusion. No etiology is found in
      as many as one third of patients. Because studies evaluating different diagnostic
      approaches with eosinophilic pleural effusions are lacking, the authors suggest
      that certain noninvasive and invasive diagnostic tools must be used based on the
      patient's clinical characteristics.

PMID- 12806237
TI  - Hepatic hydrothorax.
AB  - A hepatic hydrothorax is a pleural effusion that develops in a patient with
      cirrhosis and portal hypertension in the absence of cardiopulmonary disease. The
      pleural effusion is derived from ascitic fluid that enters the chest because of
      the negative pressure within the pleural space via defects in the diaphragm. The
      peritoneal-to-pleural flow of fluid can be demonstrated by nuclear scanning, even
      when the ascites is not clinically apparent. The pleural fluid usually has the
      characteristics of a transudate. However, an occasional patient with hepatic
      hydrothorax will develop spontaneous bacterial pleuritis manifest by increased
      pleural fluid neutrophils or a positive bacterial culture and will require
      antibiotic therapy. Treatment of the hydrothorax is directed at the underlying
      liver disease but a dyspneic patient can obtain relief from a thoracentesis or
      paracentesis. When medical therapy fails, liver transplantation is the treatment
      of choice. Both transjugular intrahepatic portosystemic shunting and
      thoracoscopic repair of diaphragmatic defects with pleural sclerosis can provide
      symptomatic relief, but the morbidity and mortality of these procedures are high
      because of the fragile nature of the patients.

PMID- 12806238
TI  - Benign asbestos pleural diseases.
AB  - The global incidence of asbestos-related lung diseases is expected to continue to
      rise. Although much attention is devoted to malignant diseases induced by
      asbestos, benign asbestos pleural diseases (pleural plaques, benign asbestos
      related pleural effusion, diffuse pleural thickening, and rounded atelectasis)
      are common in clinical practice and often produce diagnostic difficulties. The
      authors describe the clinical features of benign asbestos-related pleural
      disease, before focusing on recent advances in radiology and on controversies
      surrounding the pathogenesis of asbestos-induced pleural injury. Advances in
      computed tomography have assisted the understanding and diagnosis of these
      diseases, and increasing evidence suggests radiologic appearances on computed
      tomography can predict impairment in pulmonary function tests. The pathogenesis
      of asbestos-induced pleural diseases has also been subject to extensive
      investigation. Asbestos fibers can provoke pleural inflammation from direct
      toxicity to mesothelial cells. Inhaled asbestos fibers can also elicit pleural
      injury indirectly via the release of growth factors and inflammatory cytokines
      from within the lung. Although progress has been made in the understanding of the
      mechanisms of asbestos pleural injury, many important questions remain
      unanswered. The role of genetic factors and possible environmental cofactors (eg,
      simian virus 40) in the pathogenesis of benign asbestos pleural diseases requires
      further research.

PMID- 12806239
TI  - Management of primary spontaneous pneumothorax.
AB  - The optimal management of primary spontaneous pneumothorax remains the subject of
      considerable controversy. During the last few years, however, interesting new
      data on pathogenesis and various treatment techniques have been published, which
      have led to the publication of some interesting and thought-provoking opinion
      articles. The author reviews the latest developments in pneumothorax
      pathophysiology and management.

PMID- 12806240
TI  - What size chest tube? What drainage system is ideal? And other chest tube
      management questions.
AB  - Chest tubes and their accompanying pleural drainage units continue to present
      challenging questions regarding their optimal use. Appropriate chest tube size
      selection to accommodate the clinical situation is key, especially in the setting
      of large pleural air leaks lest a tension pneumothorax ensue. Connection of an
      appropriate pleural drainage unit to the chest tube is equally important to
      obviate impeding airflow after successful evacuation by the chest tube. Large
      bore chest tubes are generally required for patients with pneumothoraces,
      regardless of etiology, if the patient is mechanically ventilated, or for
      patients requiring drainage of viscous pleural liquids such as blood. Smaller
      bore tubes may be adequate in patients with limited production of pleural air or
      of free-flowing pleural liquid. Chest tubes may be removed successfully at either
      end expiration or end inspiration, and potentially as soon as </=200 mL/fluid
      output per day is achieved. Additional prospective studies are needed to provide
      evidence-based answers to the many questions remaining regarding chest tube
      placement, ongoing management, and removal.

PMID- 12806241
TI  - Ultrasound in the diagnosis and management of pleural disease.
AB  - The authors summarize the current applications of chest ultrasonography in the
      diagnosis and management of various pleural diseases. Ultrasound has been proved
      to be valuable for the evaluation of a wide variety of chest diseases,
      particularly when the pleural cavity is involved. Chest ultrasound can supplement
      other imaging modalities of the chest and guides a variety of diagnostic and
      therapeutic procedures. Pleural effusion, pleural thickening, pleural tumors,
      tumor extension into the pleura and even the chest wall, pleuritis, and
      pneumothorax can be detected easily and accurately with chest ultrasound. Many
      ultrasound features and signs of these diseases have been well characterized and
      widely applied in clinical practice. Under real-time ultrasound guidance the
      success rates of invasive procedures on pleural diseases increase significantly
      whereas the risks are greatly reduced. The advantages of low-cost, bedside
      availability and no radiation exposure have made ultrasound an indispensable
      diagnostic tool in modern pulmonary medicine.

PMID- 12806242
TI  - Pleural effusions in the intensive care unit.
AB  - The incidence of pleural effusions in the intensive care unit varies depending on
      the screening methods, from approximately 8% for physical examination to more
      than 60% for routine ultrasonography. Several factors contribute to the
      occurrence of pleural effusions in intensive care unit patients: large amounts of
      intravenous fluid are often administered, pneumonia is common, and heart failure,
      atelectasis, extravascular catheter migration, hypoalbuminemia, or liver disease
      are present in many intensive care unit patients. In surgical intensive care
      units, cardiac or abdominal surgery is often followed by pleural effusions, and
      in trauma patients, hemothorax is a dreaded event. Because no clinical parameter
      excludes pleural infection, and because of the impact of thoracentesis on
      diagnosis and treatment, this procedure should be performed unless
      contraindicated. Thoracentesis is safe in mechanically ventilated patients. The
      author discusses the following points regarding pleural effusions in the
      intensive care unit: screening intensive care unit patients for pleural effusion,
      safety of thoracentesis in patients receiving invasive mechanical ventilation,
      distinguishing exudates from transudates, and diagnosing and managing infected
      pleural effusions in critically ill patients. Lastly, the author suggests a
      research agenda for pleural effusions in intensive care unit patients.

PMID- 12806243
TI  - Lung cancer.

PMID- 12806244
TI  - Advances in the management of endobronchial lung malignancies.
AB  - The effective palliation of endobronchial malignancies often involves the use of
      multiple modalities including surgery, external beam radiation, chemotherapy, or
      a variety of interventional bronchoscopic techniques. The authors discuss in
      detail recent advances in interventional bronchoscopy that enhance local tumor
      control. An integrated and individualized approach to the use of these
      complementary modalities can provide rapid palliation and may improve survival in
      a subset of patients.

PMID- 12806245
TI  - Sputum cytology for the detection of early lung cancer.
AB  - Sputum cytology is an important step in the early diagnosis of
      roentgenographically occult lung cancer. It identifies primarily intraepithelial
      lesions, which are the most common squamous carcinomas not detected by helical
      CT. Patients at highest risk for lung cancer (eg, heavy smokers with airflow
      obstruction) should undergo sputum cytology. Patients with premalignant lesions
      (eg, moderate or severe dysplasia) and of course patients with carcinoma in situ
      or invasive carcinoma should receive fiberoptic bronchoscopy. The diagnosis and
      treatment of early-stage lung cancer usually has a favorable outcome. Today we
      have the knowledge and technology that can change the outcome of lung cancer
      through early identification, particularly in high-risk patients.

PMID- 12806246
TI  - Endocrine paraneoplastic syndromes in lung cancer.
AB  - Lung tumors are capable of synthesizing and secreting peptide proteins (hormones)
      that lead to a variety of endocrine paraneoplastic syndromes. Knowledge about the
      clinical manifestations, pathophysiology, and treatment of these syndromes has
      evolved over time. This article provides an up-to-date overview of this
      knowledge.

PMID- 12806247
TI  - Evaluation of operability before lung resection.
AB  - Lung resection remains the treatment of choice in the curative approach to
      nonsmall cell lung cancer. Because most lung cancer patients are current or
      former smokers, they are at increased risk of chronic obstructive pulmonary
      disease and coronary artery disease, conditions associated with increased
      surgical morbidity and mortality. Careful preoperative assessment of the
      cardiopulmonary reserves is therefore of great importance. Various single and
      combined parameters for the functional assessment before surgery have been
      proposed. Currently the emphasis is on the determination of forced expiratory
      volume in the first second, the diffusing capacity for carbon monoxide, and
      exercise testing with the measurement of maximal oxygen uptake. Adherence to
      established algorithms for this preoperative evaluation, advances in operative
      technique (video-assisted thoracoscopic surgery and combined operations of lung
      cancer surgery with lung volume reduction surgery), and perioperative care permit
      resections in patients who until recently would have been considered functionally
      inoperable.

PMID- 12806248
TI  - Contemporary management of superior pulmonary sulcus (Pancoast) lung tumors.
AB  - For more than three decades following the initial report by Shaw et al. in 1961,
      the standard treatment of Pancoast lung tumors consisted of induction
      radiotherapy followed by en bloc resection through a posterolateral thoracotomy.
      Overall 5-year survival rates with this regime were typically 30 to 40%, with
      poor prognosis in patients with positive mediastinal lymph nodes, T4 involvement,
      or incomplete resection. During the past decade, advancements in surgical
      technique and adjuvant therapy have improved the safety and completeness of
      resection as well as the probability of long-term survival. Alternative surgical
      approaches have been developed to facilitate more complete resection of tumors
      involving subclavian vessels and brachial plexus, and aggressive vertebral body
      resection has been performed in conjunction with neurosurgeons. Arguably the most
      important advance in the treatment of Pancoast tumors has been the recognition
      that induction chemoradiation substantially improves both the rate of complete
      resection and medium-term survival.

PMID- 12806250
TI  - Preformed silos in the management of gastroschisis: new progress with an old
      idea.
AB  - Outcomes for infants with gastroschisis have paralleled advances made in neonatal
      intensive care and the use of parenteral nutrition. Mortality rates approaching
      100% a half century ago are now closer to 2% to 8%. Further reduction in
      morbidity has been the focus of many studies during the past decade. Efforts have
      been made to identify factors associated with the development of gastroschisis
      and to evaluate the mode, timing, and location of delivery on the outcome of
      these infants. The effect of the mode and timing of definitive surgical repair
      has received attention by more recent reports of newer approaches, including the
      use of a preformed silo to provide coverage for the exposed viscera and allow a
      gradual reduction into the abdominal cavity.

PMID- 12806251
TI  - Laser surgery: new applications for pediatric skin and airway lesions.
AB  - Recent research pertaining to laser applications for the treatment of capillary
      malformations (port wine stains) and cutaneous and subglottic hemangiomas is
      reviewed within the context of advances in laser technology and current
      therapeutic practices and controversies. Although laser advances have resulted in
      the concomitant growth of new clinical applications, research over the past year
      has focused on refining and improving existing applications, with the ultimate
      goal of being able to individualize treatment. Research initiatives aimed at
      improving the outcomes of pulse dye laser treatment for capillary malformations
      have illustrated the complexity of the interaction between laser characteristics,
      methods of laser application, variations in human skin and tissue, and
      morphologic parameters of involved blood vessels. Investigations of cutaneous
      hemangioma have addressed the issue of early pulse dye laser intervention, and
      results of a significant prospective study clearly demonstrate that this offers
      no benefit. Studies of subglottic hemangioma have compared the outcomes of
      treatment with carbon dioxide (CO(2)) and the potassium-titanyl-phosphate lasers,
      concluding that the latter results in superior outcomes, with less risk of
      posttreatment subglottic stenosis.

PMID- 12806252
TI  - Application of laparoscopy for bariatric surgery in adolescents.
AB  - An epidemic increase in adolescent obesity in the United States has resulted in
      significant obesity-related comorbidities, previously seen only in adults.
      Although bariatric surgery is an acceptable alternative for weight loss in
      severely obese adults, no conclusions have been made about the appropriateness of
      bariatric surgery for individuals younger than 18 years old. Nonetheless,
      bariatric surgery is increasingly being performed on adolescents with clinically
      severe obesity and experience suggests that it is effective and safe. Application
      of the principles of adolescent growth, development, and compliance is essential
      to avoid adverse physical, cognitive, and psychosocial outcomes following
      bariatric surgery. Bariatric surgery should be part of a multidisciplinary
      approach to the management of adolescents with clinically severe obesity and
      should be performed by specialists dedicated to pediatric care, in institutions
      capable of meeting the guidelines for surgical treatment outlined by the American
      Society of Bariatric Surgery.

PMID- 12806253
TI  - Image-guided surgery for the pediatric patient: ultrasound, computerized
      tomography, and magnetic resonance imaging.

PMID- 12806254
TI  - Robotics and the pediatric surgeon.
AB  - Surgical robots are enabling devices for minimally invasive (laparoscopic)
      surgery (MIS). They use a computer to enhance a surgeon's skills as hand
      movements are transmitted to robotic arms. The computer filters tremor, which
      becomes important at high magnifications of 10 to 15 times available in MIS. It
      also provides motion scaling so that large hand movements are converted to very
      small movements of the robotic arm. The robotic arms also have wrists that make
      suturing and knot tying far more accurate and efficient. Surgical robots are
      currently used clinically for procedures such as MIS Nissen fundoplication,
      cholecystectomy, and splenectomy. Laboratory experience indicates that they may
      provide advantages for newborn procedures such as portoenterostomy for biliary
      atresia and repair of esophageal atresia and tracheoesophageal fistula. They have
      a potential for making possible MIS procedures, which can only be done open now,
      and for introducing entirely new procedures as well as for the performance of
      procedures by operators distant from the patient.

PMID- 12806255
TI  - Tissue engineering: current state of clinical application.
AB  - Despite several, mostly isolated successes, few controlled, prospective trials
      have yet validated clinical tissue engineering applications. Although this may,
      at least in part, be explained by the very young age of this field, tissue
      engineering involves the need for an elaborate and expensive infrastructure, not
      to mention qualified personnel. This translates into an inherent difficulty in
      establishing multicenter trials. Moreover, companies mostly devoted to tissue
      engineering have yet to prove themselves economically viable. On the other hand,
      although very few engineered tissues have been approved by the US Food and Drug
      Administration (FDA), more than 70 companies have recently been developing new
      products. Many challenges are yet to be overcome before "off-the-shelf" tissues
      can be offered commercially. Nevertheless, given the scientific promise,
      potential social impact, and young age of the field, many believe that it should
      be only a matter of time until tissue engineering reaches the mainstream of
      surgical practice.

PMID- 12806256
TI  - Decision analysis and clinical uncertainty.
AB  - Decision analysis is a tool to aid decision-making in the face of uncertainty.
      Typically, clinical decision-making involves the selection of one or more
      therapeutic alternatives when the outcome of that decision cannot fully be known
      at the time the decision must be made. Uncertainty derives from imperfections in
      diagnostic testing, uncertainty about the natural history of disease, the random
      nature of iatrogenic complications, and the impact of patient-specific factors or
      comorbid conditions. Decision analysis seeks to optimize the expected outcome of
      a decision, incorporating the probabilistic nature of this uncertainty. Decision
      analysis is applied here to a common problem in intensive care units-the
      treatment of suspected ventilator-associated pneumonia. Recent applications of
      decision analysis in the pediatric literature are also used to illustrate the
      scope and limitations of this tool in clinical practice.

PMID- 12806257
TI  - Toll-like receptor signaling in sepsis.
AB  - Despite extensive research, bacterial sepsis and its associated systemic
      inflammation remain a major cause of morbidity and mortality in the pediatric
      intensive care unit. Advances in molecular biology, however, have improved our
      understanding of this disease process and have opened up new avenues of potential
      therapeutic approaches. One such exciting area has been the substantial and still
      growing evidence that the mammalian immune system uses a family of Toll-like
      receptors (TLRs) to generate a response to molecular patterns present on invading
      microorganisms. In particular, TLR4 is part of a recognition complex for
      bacterial lipopolysaccharide (LPS), thus raising the likelihood of its
      involvement in the inflammatory response to bacterial sepsis. This review
      highlights our understanding of the molecular biology of these receptors,
      focusing on the LPS response, and concluding with a summary of ongoing evaluation
      and potential therapeutic strategies for treating sepsis through blockade of TLR
      signaling.

PMID- 12806258
TI  - Outcome of coma in children.
AB  - Coma following a hypoxic-ischemic event is a serious condition and common reason
      for admission to the pediatric intensive care unit. Because coma has a high rate
      of mortality and morbidity in children, and the clinician may be unsure of the
      outcome very early in the course, it is important to have strategies to define
      prognosis. Although most studies have been conducted in adults, we review factors
      predicting outcome from coma of nontraumatic causes in infants and children. We
      consider the relation between physical findings, commonly accessible laboratory
      tools, and outcome, and comment on some newer techniques that may become more
      available for clinical purposes.

PMID- 12806259
TI  - Brain death in children.
AB  - In 1981, the Report of the Medical Consultants on the Diagnosis of Death
      established guidelines for the diagnosis of brain death and, in 1995, the
      American Academy of Neurology published practice parameters to standardize
      determination of brain death. In 1987, the American Academy of Pediatrics
      established guidelines for determining brain death in children. Despite the
      establishment of these guidelines, the declaration of "death" based on the
      cessation of brain function remains complex and controversial. In this review are
      discussed the current guiding principles and the controversies in the diagnosis
      of brain death in children.

PMID- 12806260
TI  - Family member presence in the pediatric emergency department.
AB  - Traditionally, family members were excluded from viewing invasive procedures and
      cardiopulmonary resuscitation in the pediatric emergency department. The concept
      of family-centered care in the emergency department has now become more
      widespread. Consequently, family member presence during routine invasive
      procedures such as venipuncture, intravenous cannulation, urethral
      catheterization, and lumbar puncture has become more accepted. Survey evidence
      indicates parents' overwhelming desire to be present for invasive procedures and
      cardiopulmonary resuscitation. Healthcare provider opinions about family
      witnessed resuscitation lack similar uniformity. Variations in approval of
      witnessed resuscitation are influenced by occupation, level of training and
      experience, and prior exposure to family member presence practices. Although
      several organizations formally support family presence policies, citing benefits
      for grieving relatives, critics point to a lack of rigor in a large body of the
      research cited to underpin these endorsements. We review the literature from the
      perspective of pediatric emergency physicians, offer suggestions for family
      member presence, and provide directions for future study.

PMID- 12806261
TI  - Accidental and abusive head injury in young children.
AB  - Children commonly present for medical care after sustaining head trauma. In
      children younger than 2 years of age, the practitioner must distinguish
      accidental head injury from abusive head injury. The following article discusses
      the evaluation of children with head injury and how to make the distinction
      between accidental and abusive head injury.

PMID- 12806262
TI  - Advances in clinical forensic medicine.
AB  - Clinical forensic medicine is the branch of medicine that deals specifically with
      cases involving both legal and medical aspects of patient care. A forensic
      evaluation refers to the detection, collection, and preservation of evidence.
      Pattern injury recognition, interpretation of injuries, documentation of
      testimonial and injuries (including photography), reporting requirements, and
      regulations are all vital components of a forensic evaluation, but are rarely the
      topic of discussion in training hospitals. Medical professionals working in
      prehospital care and acute care settings are likely to encounter perplexing
      forensic issues related to child abuse, sexual assault, or unexpected childhood
      death in their practice. This article focuses on the most recent insights related
      to sexual assault and forensic evidence as it relates to successful prosecution,
      shaken baby syndrome, and pediatric nonaccidental thermal injury. Also reviewed
      are the most current publications related to clinical forensic medicine for the
      year 2002, incorporating practical clinical tips from the most informative
      articles from the past decade.

PMID- 12806263
TI  - Newborn screening for cystic fibrosis.
AB  - Early diagnosis of cystic fibrosis (CF) provides an opportunity to improve
      disease control and prevent early complications. Of patients with CF in the
      United States, 10% are identified early through newborn screening (including
      infants born in Colorado, Massachusetts, New Jersey, New York, Wisconsin,
      Wyoming, and parts of California, Connecticut, Pennsylvania, and Montana).
      Successful screening programs in these states have stimulated other states to
      consider adding CF screening to their newborn programs. Additionally, new
      technology permits expanded screening for numerous genetic conditions. Genetic
      screening, such as that used most frequently for CF, creates new challenges for
      the clinician, including atypical disease presentations and carrier detection. In
      this review, we examine the many advances in CF newborn screening and early care
      that were reported during the last few years.

PMID- 12806264
TI  - Infant pulmonary function testing.
AB  - Pulmonary function tests in infants have been used for many years, but they have
      been largely relegated to specialized centers and research purposes. More
      recently, development of commercial equipment and newer techniques has allowed
      for more broad use and application of these tests. This review describes
      different techniques that have been used to study infants and toddlers, and their
      clinical applications.

PMID- 12806265
TI  - Update on pediatric nutrition: breastfeeding, infant nutrition, and growth.
AB  - Recent studies continue to point out the critical nature of a patient's
      nutritional status in helping to determine important health outcomes in
      pediatrics. We review recent data concerning the composition of breast milk and
      its adequacy to support infant growth in the first six months of life, as well as
      trials that support breastfeeding as an important method to delay or reduce the
      incidence of atopic diseases such as eczema, allergies, and asthma. Studies have
      also been published that show how physician education and training about
      breastfeeding can be optimized. Studies showing how nutritional status is
      measured (using standard anthropometric techniques as well as more modern
      measures of basal metabolic rate) are highlighted, as well as the role of
      micronutrient supplementation of patients with the human immunodeficiency virus
      infection and diarrheal diseases.

PMID- 12806266
TI  - A 12-day-old infant with hypoglycemia.

PMID- 12806268
TI  - How common are gastrointestinal disorders in children with autism?
AB  - We could identify no report that describes the prevalence of gastrointestinal
      disorders in a representative group of children with a diagnosis of autism
      compared with appropriate controls. Thus, we found no evidence upon which to base
      a confident conclusion as to whether gastrointestinal symptoms are more common in
      children with than without autism. However, the frequency of gastrointestinal
      symptoms observed in population-based samples of autistic children indicate that
      gastrointestinal problems are not nearly as common in children with autism as
      reports from pediatric gastroenterology clinics suggest.

PMID- 12806269
TI  - What is the evidence basis for existing treatments of eating disorders?
AB  - Most existing treatments of eating disorders (ED) produce a period of remission
      that is short lived and expressed in fewer than 50% of the patients.
      Antidepressants (eg, selective serotonin reuptake inhibitors [SSRI]) have a small
      effect in bulimia nervosa and they are not recommended in anorexia nervosa (AN)
      because serotonin inhibits food intake. In a randomized, controlled trial,
      training of eating behavior and satiety, supply of warmth, reduction of physical
      hyperactivity, and restoration of social activities brought 75% of patients with
      ED into remission, and 93% remained in remission during follow-up. Further
      randomized, controlled trials comparing presently used interventions will provide
      the evidence needed to improve the treatment of ED.

PMID- 12806270
TI  - Management of anorexia nervosa with exercise and selective serotonergic reuptake
      inhibitors.
AB  - Treatment of patients with anorexia nervosa is a topic that continues to spark
      debate. Two particular areas of controversy include the role of exercise and the
      use of selective serotonergic reuptake inhibitors (SSRI). Few randomized
      controlled trials have addressed these two issues. The psychological impact of
      exercise in patients with anorexia nervosa is complex, and exercise may have a
      negative impact on bone health. No data support the use of selective serotonergic
      reuptake inhibitors for weight recovery, but a role may exist for their use in
      prevention of relapse. More research is needed to define more clearly the role of
      both exercise and selective serotonergic reuptake inhibitors in the treatment of
      patients with anorexia nervosa.

PMID- 12806272
TI  - To bead or not to bead.
AB  - To bead or not to bead, that is the question posed by Ito et al. in this issue of
      the Journal of Immunotherapy. The generation of tumor-reactive T cells remains a
      major impediment to the wider application of adoptive cell transfer (ACT) therapy
      for the treatment of patients with cancer. Ito et al. used lymph nodes of mice
      draining implanted sarcomas as an enriched source of tumor antigen-specific
      cells. They investigated the ex vivo activation of the lymph node cells by
      artificial antigen presenting cells (aAPCs) for the production of therapeutic T
      cell cultures. The optimal aAPC consisted of magnetic beads coated with anti-CD3
      and anti-CD28 antibodies. Short-term ex vivo culture with the aAPCs led to a
      selective expansion and/or activation of tumor antigen specific CD4+ cells. These
      results lay a solid foundation for the clinical application of bead-based T cell
      activation, and promote efforts to develop the therapeutic strategy of in vivo
      immunization, ex vivo T cell activation, and adoptive cell transfer.

PMID- 12806273
TI  - Interleukin-2-independent proliferation of human melanoma-reactive T lymphocytes
      transduced with an exogenous IL-2 gene is stimulation dependent.
AB  - A major obstacle limiting the efficacy of adoptive T-cell transfer (adoptive
      immunotherapy) to treat patients with cancer is the short survival of the
      transferred cells. These in vitro activated T cells depend on the growth factor,
      interleukin (IL)-2, and may undergo apoptosis in vivo when they are transferred.
      The authors previously reported that the need for an exogenous source of IL-2
      could be abrogated in vitro by retrovirally transducing antitumor T lymphocytes
      with an exogenous IL-2 gene. Here they report that this growth of IL-2
      transductants depended on restimulation of the T-cell receptor complex and
      appeared to be regulated at the transcriptional level of the transduced IL-2
      gene. The transduced IL-2 transcript was barely detectable in IL-2-transductants
      just before they died without restimulation, and they expressed a low level of
      the CD25 molecule, the alpha chain of the IL-2 trimeric receptor complex.
      Melanoma-specific tumor-infiltrating lymphocytes (either bulk or CD8+ cells
      alone), when transduced with an IL-2 retroviral vector, could produce IL-2 upon
      tumor stimulation and proliferated after the destruction of autologous tumor
      cells in the absence of added IL-2. Control vector-transduced tumor-infiltrating
      lymphocytes failed to do so under the same conditions. These findings provide a
      foundation for the development of clinical efforts to adoptively transfer
      melanoma-specific tumor-infiltrating lymphocytes transduced with an IL-2
      retroviral vector for the treatment of patients with metastatic melanoma to
      evaluate the fate and therapeutic effect of these IL-2 gene-modified antitumor T
      lymphocytes in vivo.

PMID- 12806274
TI  - Biologic activity of polyethylene glycol12000-interferon-alpha2b compared with
      interferon-alpha2b: gene modulatory and antigrowth effects in tumor cells.
AB  - The relative activities of interferon-alpha2b (IFN-alpha2b) and polyethylene
      glycol(12000)-IFN-alpha2b (PEG-IFN-alpha2b) were assessed in cell culture studies
      using WM9 melanoma or ACHN renal cell carcinoma cell lines. Interferon-alpha2b
      and PEG-IFN-alpha2b had identical antiproliferative activities when tested in
      cell proliferation studies conducted with equivalent antiviral units of each IFN
      preparation. Neither IFN formulation was effective in inducing apoptosis in WM9
      melanoma cells, but both increased slightly the percentage of ACHN cells
      undergoing apoptosis as assessed by Annexin V staining. Interferon-alpha2b and
      PEG-IFN-alpha2b both activated signal transducer and activator of transcription
      complexes, and the duration of complex activation was similar for both IFN
      formulations. Induction of different IFN-stimulated genes was assessed by
      Northern blotting and the quantitative real-time reverse transcription-coupled
      polymerase chain reaction (RT-PCR) in WM9 melanoma, ACHN renal cell carcinoma,
      U937 lymphoma, and MOLT-4 and Mono Mac 6 leukemia cell lines. Interferon-alpha2b
      and PEG-IFN-alpha2b had equivalent gene-modulatory activities within each of
      these tumor cell lines, although cell line-specific induction patterns were
      observed. When compared with the antiviral 50% inhibitory concentration (IC(50))
      values, the dose-dependent gene expression data correlated with cell sensitivity
      to IFN treatment. Together, the drug comparability and cell sensitivity data
      suggest a predictive relation between dose, time, antiviral activity, and gene
      transcription effects. Therefore, although the specific activity of IFN-alpha2b
      is approximately three times greater than PEG-IFN-alpha2b, the two preparations
      have identical in vitro biologic activities when applied to cells at equivalent
      antiviral units.

PMID- 12806275
TI  - Identification of a naturally processed HLA-DR-restricted T-helper epitope in
      Epstein-Barr virus nuclear antigen type 1.
AB  - Epstein-Barr virus nuclear antigen type 1 (EBNA1), the only viral protein that is
      unequivocally expressed in all Epstein-Barr virus (EBV)-associated malignant
      diseases, is essential for viral DNA replication and maintenance of the viral
      episome in infected cells. A glycine-alanine repeat domain inhibits antigen
      processing through the ubiquitin-proteasome pathway for presentation on human
      leukocyte antigen (HLA) class I molecules. EBNA1 is not protected from the HLA
      class II processing pathway, and CD4+ HLA class II-restricted T cells recognize
      the antigen. CD4+ T-helper (Th) cells play critical roles in initiating,
      regulating, and maintaining immune responses against viral infections and tumors,
      so that inclusion of EBNA1 as a target antigen may improve immunotherapy for EBV
      associated cancers. In this study, the authors used the TEPITOPE software program
      to predict promiscuous class II epitope candidates. After several HLA-DR
      restricted peptides were identified by in vitro analysis of the T-cell response
      to synthetic peptides, a T-cell clone was established that was specific for one
      of the peptides. Functional studies were performed with this clone. The CD4+ T
      helper cells specific for the HLA-DR15-restricted peptide EBNA1(482)
      (AEGLRALLARSHVER) recognized naturally processed EBNA1 protein. This epitope was
      presented by several HLA-DR alleles, including DR4, DR7, and DR11. The inclusion
      of the promiscuous, naturally processed EBNA1(482) epitope in vaccine constructs
      could enhance immune responses against EBV-positive cancers.

PMID- 12806276
TI  - Antitumor reactivity of anti-CD3/anti-CD28 bead-activated lymphoid cells:
      implications for cell therapy in a murine model.
AB  - Ligation of TCR and CD28 expressed on T cells via mAbs results in activation of T
      cells capable of tumor destruction in adoptive immunotherapy. In a murine model,
      the authors examined in vitro activation conditions utilizing plate-immobilized
      and bead-conjugated mAbs that bind to CD3 and CD28. Bead-activated tumor-draining
      lymph node (TDLN) cells demonstrated superior cytokine (IFN-gamma, GM-CSF, IL-2,
      and IL-10) secretion and mediated tumor regression more efficiently compared with
      plate-activated cells. The bead-activated TDLN cells had a significantly higher
      percentage of CD4+ cells compared with plate-activated cells. On a per-cell
      basis, positively selected CD4+ cells activated with bead-coupled or plate
      immobilized mAbs mediated tumor-specific regression equally. Bead-activated CD4+
      TDLN cells demonstrated significantly higher levels of tumor specific IL-2
      secretion compared with plate-activated CD4+ cells that may provide helper
      function to CD8+ effector cells. The antitumor reactivity of bead-activated
      lymphoid cells depended upon their source. TDLN cells after bead activation were
      more potent than splenocytes from tumor-bearing hosts in mediating tumor
      regression in vivo. Bead-activated LN cells and splenocytes from nontumor-bearing
      hosts demonstrated nonspecific cytokine secretion and minimal efficacy in
      adoptive immunotherapy. At minimal doses of IL-2, the antitumor reactivity of
      bead-activated TDLN cells was significantly enhanced. Anti-CD3/anti-CD28 bead
      activation of tumor-primed T cells represents an efficient method to generate
      effector cells for immunotherapy.

PMID- 12806277
TI  - Combined treatment with interleukin-18 and low-dose interleukin-2 induced
      regression of a murine sarcoma and memory response.
AB  - Among cytokines applied for immunotherapy of cancer, one of the most successful
      approaches to date involves systemic delivery of high-dose interleukin (IL)-2.
      However, the clinical utility of high-dose IL-2 has been limited by significant
      adverse effects, including vascular leak syndrome. Given this limitation, many
      attempts to decrease the dosage of IL-2 while maintaining its antitumor
      therapeutic effects are being made. In this study, the authors observed that
      combined use of IL-18 and low-dose IL-2 synergistically promoted in vitro
      proliferation of natural killer cells with up-regulation of IL-2 receptor-alpha
      and also synergistically stimulated cytolytic activity and interferon-gamma
      production by these cells. Furthermore, intratumoral injections of these two
      cytokines completely eradicated day-12 established subcutaneous tumor and induced
      CD4+-dependent memory in a MCA205 murine tumor model. Observed primary antitumor
      responses depended largely on natural killer cells and partly on CD8+ T cells.
      Fas-L pathway and interferon-gamma production were critical in tumor eradication.
      These results indicate that combined administration of IL-18 and low-dose IL-2
      could be a new model for cancer immunotherapy, which probably engages the
      activation of natural killer cells through interferon-gamma- and Fas-L-dependent
      pathways.

PMID- 12806278
TI  - Large-scale expansion of dendritic cell-primed polyclonal human cytotoxic T
      lymphocyte lines using lymphoblastoid cell lines for adoptive immunotherapy.
AB  - Dendritic cells (DCs) have been shown to activate cytotoxic T-lymphocytes (CTLs)
      for many tumor and virus-associated antigens in vitro. In this study, the authors
      tested the feasibility of using DCs to expand polyclonal, cytomegalovirus (CMV)
      specific CTL lines for adoptive immunotherapy. Two stimulations with DCs
      expressing pp65, the immunodominant antigen of CMV, effectively activated and
      expanded MHC-class I restricted, CMV-specific CTLs from peripheral blood
      mononuclear cells. However, limiting monocyte-derived DC numbers precluded the
      authors from expanding the CTLs to the numbers required for adoptive transfer
      protocols. Nonspecific stimulation methods failed to expand CTL lines
      specifically. However, the authors found that lymphoblastoid cell lines (LCLs)
      expressing pp65 expanded pp65-specific CTL lines without competition from EBV
      specific CTLs. An unlimited source of antigen presenting cells that could present
      antigen in the appropriate MHC context emerged as a critical point for expansion
      of polyclonal, antigen-specific CTL lines.

PMID- 12806279
TI  - Generation of melanoma-specific cytotoxic T lymphocytes for allogeneic
      immunotherapy.
AB  - To exploit alloreactive T-cell responses known as the graft-versus-tumor effect,
      allogeneic hematopoietic stem cell transplantation is being explored as
      experimental therapy in selected solid tumors, including metastatic melanoma.
      However, donor T-cell responses are often delayed and associated with severe
      graft-versus-host disease. Posttransplant adoptive immunotherapy using tumor
      specific cytotoxic T lymphocytes (CTL) of donor origin might provide immediate
      graft-versus-tumor effects but not graft-versus-host disease. Therefore, the aim
      of the current study was to define in vitro conditions for the expansion of
      allogeneic major histocompatibility complex-matched CTLs targeting melanoma
      associated antigens (MAA). The CTLs were generated from peripheral blood
      mononuclear cells (PBMCs) of HLA-A*0201+ healthy donors by repetitive
      stimulations with HLA-A*0201-restricted MAA-derived peptides. Melanoma
      reactivity, as determined by lysis of peptide-pulsed T2 cells and HLA-A2+/Ag+
      melanoma cells, was detected using in vitro expanded CTL targeting MAA peptides
      AAGIGILTV(MT(27-35)), IMDQVPFSV(G(209-2M)), and YMDGTMSQV(T(368-376)). In
      contrast, FLWGPRALV(MAGE3(271)-(279)) and VLPDVFIRCV(GnT-V(nt38-67)) induced
      peptide-specific recognition of T2 target cells only, whereas ITDQVPFSV(G(209
      217)), KTWGQYWQV(G9(154)), MLLAVLYCL(T(1-9)), and tumor lysate could not induce
      specific CTLs. Specific cytolytic activity was accompanied by interferon-gamma
      secretion. Peptide-pulsed dendritic cells were required only for the initial
      stimulation of CTLs and could be substituted by PBMCs during restimulations. The
      median expansion rate of CTL was five to six times, regardless of whether
      dendritic cells or PBMCs were used after the initial stimulation. The results
      delineate the conditions for effective ex vivo expansion of melanoma-specific
      CTLs from PBMCs of healthy donors to be used as an adjunct in allogeneic cell
      therapy of metastatic melanoma.

PMID- 12806280
TI  - Intraperitoneal fluid neopterin, nitrate, and tryptophan after regional
      administration of interleukin-12.
AB  - Activated monocytes-macrophages may be associated with antitumor activity, and
      activation of these cells by certain cytokines, primarily interferon gamma (IFN
      gamma), can be indicated by alterations in the concentrations of neopterin,
      nitrate, or tryptophan. Specimens of peritoneal fluid were obtained from patients
      with intra-abdominal neoplasia who were undergoing treatment in a phase I trial
      of weekly intraperitoneal recombinant interleukin-12 (rhIL-12), an inducer of IFN
      gamma. Concentrations of neopterin, nitrate, tryptophan, IFN-gamma, and tumor
      necrosis factor alpha (TNF-alpha) were determined at various times during the
      first 48 hours in 11 patients who received intraperitoneal rhIL-12 in doses
      ranging from 100 to 1,500 ng/kg. An increase in peritoneal fluid nitrate
      concentrations was observed in nine of these patients. Increased concentrations
      of TNF-alpha and IFN-gamma were detected in 3 of 9 and 8 of 11 patients,
      respectively. Increased peritoneal fluid neopterin concentrations were detected
      by 24 hours after the injection in all patients studied. A significant increase
      in the ascitic fluid neopterin level could still be detected after 1 or 2 weeks
      of treatment (mean +/- standard error, 7.8 +/- 1.5 nM vs. 4.6 +/- 0.3 nM;
      Wilcoxon test, p = 0.0019), which is consistent with monocyte-macrophage
      activation. In contrast, the tryptophan concentration was lower (4.7 +/- 1.1
      microM vs. 6.1 +/- 1.2 microM; p = 0.0428) after 1 or 2 weeks of treatment. There
      was a significant correlation between the dose of rhIL-12 and posttreatment
      neopterin concentrations (r(s) = 0.559, p = 0.0102). The intraperitoneal delivery
      of rhIL-12 appears to be associated with an immediate, sustained, and dose
      dependent increase in peritoneal fluid neopterin, associated in most patients by
      an increase in IFN-gamma and in certain patients by an increase in nitrate and a
      decrease in tryptophan concentrations.

PMID- 12806281
TI  - Serum total ganglioside level correlates with clinical course in melanoma
      patients after immunotherapy with therapeutic cancer vaccine.
AB  - The authors tested the hypothesis that the therapeutic destruction of residual
      tumors may be reflected in the level of serum total gangliosides (sTG). The sTG
      level was evaluated in 17 patients with in-transit melanoma and 70 patients with
      resected regional node metastasis, who have received a polyvalent therapeutic
      melanoma cell vaccine. The treatment response was determined by regression of in
      transit metastases or by overall survival after resection. sTG levels were
      measured, blinded, before and after immunotherapy. The mean sTG level of the in
      transit melanoma patients increased from 18.57 +/- 3.18 mg/dL pretreatment to
      23.7 +/- 5.5 mg/dL between weeks 2 and 16 after initiation of treatment (p(2) <
      0.0001). By week 24, the level had returned to its prevaccine level in the seven
      clinical responders (18.1 +/- 2.3 mg/dL vs. 20.4 +/- 3.2 mg/dL; p(2) < 0.050) but
      remained higher than its prevaccine level in the 10 nonresponders (23.3 +/- 5.1
      mg/dl vs. 17.2 +/- 2.7 mg/dL). Similarly, the sTG level of the patients with
      nodal metastases increased between weeks 2 and 16 after the first vaccine
      treatment; by week 24, it had returned to pretreatment level in patients who
      survived more than 56 weeks but remained significantly elevated (p(2) < 0.01) in
      patients who survived less than 56 weeks. The sTG level increased between weeks 2
      and 16 in all vaccine recipients and returned to prevaccine level by week 24 in
      all who showed measurable regression of in-transit melanoma (7 of 17 patients) or
      improved overall survival (53 of 70 patients). The data suggest that sTG level
      could be a potential tool for assessing the response to immunotherapy in melanoma
      patients by week 24.

PMID- 12806282
TI  - Outpatient experience with moderate dose bolus interleukin-2 in metastatic
      malignant melanoma and kidney cancer.
AB  - Twenty patients with either melanoma ( 7) or kidney cancer ( 13) were treated
      with outpatient bolus interleukin (IL)-2 18-22 MIU/m2 IVPB for 3 consecutive days
      for 6 consecutive weeks followed by a 2-week rest break (on an 8-week cycle).
      Patient characteristics included 16 males/4 females, eleven patients had received
      no prior systemic therapy, median ECOG performance status = 1, and most common
      disease sites being lung, lymph node, subcutaneous, bone, and liver. Two patients
      with melanoma (29% response rate) (95% CI: 8-64%) and two with kidney cancer
      (15%) (95% CI: 3-43%) have achieved partial responses. Two minor responses in
      kidney cancer were also seen. The most common toxicities were nausea, fatigue,
      rigors, fever, and myalgias/arthralgias. No cardiac events occurred, and no
      patients required hospitalization due to toxicity. IL-2 at this outpatient dose
      and schedule is well tolerated and displays some evidence of activity in melanoma
      and kidney cancer. Larger patient numbers are required to corroborate these
      response rates and to determine whether complete responses are possible.

PMID- 12806283
TI  - Detection of Chlamydia pneumoniae in cholesteatoma tissue: any pathogenetic role?
AB  - BACKGROUND: Acquired cholesteatoma is a complication of chronic otitis media that
      is usually associated with an intense local inflammatory reaction. Cholesteatoma
      probably arises from epithelial migration close to an ongoing host inflammatory
      response attributable to a chronic bacterial infection. Chlamydia pneumoniae is
      an intracellular microorganism associated with several pathologic conditions
      originally considered noninflammatory, including asthma, atherosclerosis, and
      Alzheimer disease. To investigate a possible relationship between C. pneumoniae
      and the development of cholesteatoma, tissue was studied in three different
      layers by polymerase chain reaction analysis. The results were compared with
      those relative to other two common middle-ear pathogens, Mycoplasma pneumoniae
      and Haemophilus influenzae. METHODS: Cholesteatoma specimens were collected from
      32 patients undergoing middle ear surgery. A series of 5 microm-thick specimens
      were obtained at three different tissue levels, internal (matrix), intermediate
      (perimatrix), and external (granulation tissue), and processed by polymerase
      chain reaction for detection of C. pneumoniae, H. influenzae, and M. pneumoniae.
      Fragmentation and polymerase chain reaction amplification were carried out using
      two substantially different techniques. RESULTS: C. pneumoniae was detected with
      either polymerase chain reaction techniques in the internal layers in 16 of the
      32 cholesteatomas (50%), associated with a positive finding in the intermediate
      layer in two cases and in the external layer in one case. Four specimens
      contained H. influenzae, always in the external layer, whereas none contained M.
      pneumoniae. CONCLUSIONS: The close relationship between cholesteatoma and C.
      pneumoniae demonstrated by the findings of this study could suggest a direct
      cause and effect link between the pathogen action and the clinical
      manifestations. Otherwise, a facilitated colonization by C. pneumoniae and
      chronic pathology of the ear could both take origin from a peculiar immunologic
      background of the host.

PMID- 12806284
TI  - Pars flaccida displacement pattern in purulent otitis media in the gerbil.
AB  - HYPOTHESIS: Our hypothesis is that purulent otitis media and otitis media with
      effusion cause stiffness loss of the tympanic membrane. This loss of stiffness
      may be persistent and precede the development of retraction pockets and
      cholesteatoma. BACKGROUND: Postinflammatory changes such as retraction pockets
      and cholesteatoma develop in the pars flaccida and in the pars tensa of the
      tympanic membrane. In our previous experimental studies, stiffness changes were
      shown to develop early in the pars tensa in response to purulent otitis media and
      otitis media with effusion. These changes are suggested to be precursors to a
      later development of retraction pockets and cholesteatoma. In the clinical
      situation, retraction pockets are often found in the pars flaccida only. The aim
      of the current study was thus to investigate whether stiffness changes appear
      also in the pars flaccida during purulent otitis media. METHODS: Streptococcus
      pneumoniae type 3 was injected into the middle ear to induce purulent otitis
      media. As a measure of pars flaccida stiffness, peak displacement versus middle
      ear pressure was used. The peak displacement measurements were obtained from full
      field moire; interferometry, which is a noncontacting optical technique for
      deformation measurements. RESULTS: Ears with purulent otitis media showed
      increased peak displacement of the pars flaccida at a middle ear pressure of 200
      daPa, compared with normal controls. CONCLUSION: There was a decreased mechanical
      stiffness of the pars flaccida in acute purulent otitis media. This decreased
      stiffness may predispose for future retraction pocket formation and cholesteatoma
      development.

PMID- 12806285
TI  - Eustachian tube goblet cell density during and after acute otitis media caused by
      Streptococcus pneumoniae: a morphometric analysis.
AB  - BACKGROUND: Prior investigations have shown that the number of mucus-producing
      goblet cells in the middle ear mucosa is highly increased during and up to at
      least 6 months after experimental acute otitis media. This may, in conjunction
      with deteriorated eustachian tube function, predispose to subsequent development
      of secretory otitis media. One reason for the deteriorated tubal function after
      acute otitis media has been suggested to be an excessive accumulation of mucus
      secretions, blocking the tube and thereby clearance of the middle ear. This
      investigation determines the density of the mucus-producing goblet cells in the
      eustachian tube during and up to 6 months after experimental acute otitis media.
      METHODS: Middle ear inoculation of Streptococcus pneumoniae in 25 rats. Groups of
      five animals, killed on Days 4, 8, 16, 90, and 180. Dissection and
      decalcification of the eustachian tube, followed by paraffin embedding and serial
      transverse sectioning, periodic acid-Schiff/Alcian blue staining and morphometric
      determination of the goblet cell density in every 20th section, using a light
      microscope. RESULTS: The goblet cell density was increased on Day 8 and later in
      the tympanic orificium, in addition to the tympanic and midportion third of the
      tube. Increased goblet cell density was seen in the pharyngeal third on Days 8
      and 16, whereas no changes were registered in the pharyngeal orificium.
      Pathologic intraepithelial glands formed after the infection and goblet cells
      were found in mucosal areas normally devoid of these. CONCLUSIONS: The eustachian
      tube goblet cell density is increased during and up to 6 months after acute
      otitis media. Indicated excessive secretion of mucus by more goblet cells may
      contribute to the deteriorated eustachian tube function found after acute otitis
      media and thus predispose, sustain, or aggravate middle ear disease.

PMID- 12806286
TI  - The effects of hyaluronic acid, epidermal growth factor, and mitomycin in an
      experimental model of acute traumatic tympanic membrane perforation.
AB  - HYPOTHESIS: The goal of this study was to evaluate the effects of hyaluronic
      acid, epidermal growth factor, and mitomycin C on the healing of acute
      experimental traumatic perforations of the tympanic membrane. BACKGROUND: Most
      acute perforations of the tympanic membrane heal spontaneously. However, some
      form of surgical treatment (i.e., myringoplasty) is needed for nonhealing
      perforations. Because the closure occurs by squamous epithelial migration, drugs
      that stimulate this regenerative process may aid in the closure of the
      perforation, obviating the need for more extensive treatments. METHODS: Bilateral
      perforations of the tympanic membrane were created in 30 rats, divided into three
      groups (A, B, C). The perforations in the right ears were treated with hyaluronic
      acid, epidermal growth factor, or mitomycin C. Those in the left ears were left
      untreated for comparison. To examine the healing process in different periods, 5
      animals were killed in each group at days 3, 5, 7, 9 and 14. The other 5 animals
      in each group were observed daily to determine the duration of perforation
      closures. Thirty surgical specimens (5 right sides from each group and all 15
      left sides in all groups) were histopathologically examined for tympanic membrane
      thickness, fibroblastic reaction, neovascularization, and crust morphology.
      RESULTS: Hyaluronic acid and epidermal growth factor applications significantly
      shortened the healing in acute experimental traumatic perforations of the
      tympanic membrane (p = 0.0432); however, the difference between them was not
      significant (p = 0.3160). On the other side, tympanic membrane perforations
      treated with topical mitomycin C showed no evidence of closure. There were no
      significant differences in the histologic parameters between the treated groups
      and their contralateral control ears. CONCLUSION: Hyaluronic acid and epidermal
      growth factor accelerated the closure of acute tympanic membrane perforations in
      rats. This may make them clinically useful in augmenting the efficiency of
      conservative treatments of acute perforations of the tympanic membrane.

PMID- 12806287
TI  - Why is otosclerosis of low prevalence in Japanese?
AB  - OBJECTIVE: This study aimed to clarify the reasons why clinical otosclerosis, a
      very common disease among Caucasians, is not prevalent among Japanese. STUDY
      DESIGN: The incidence, site, activity, and volume of otosclerotic foci were
      examined in 1011 temporal bone sections from 507 Japanese individuals. SETTING:
      This study was prepared at the temporal bone laboratory, Fukushima Medical
      University, Fukushima. RESULTS: Otosclerotic foci were observed in 2.56% of
      individuals and in 1.48% of the ears. The most common site of involvement was
      anterior to the oval window region, but this was only in 38.9% of the ears with
      otosclerotic foci. The otosclerotic foci were not involved in the
      stapediovestibular articulation or the endosteal layer of the otic capsule in any
      ears. An active change of the otosclerotic focus was seen in 33.3% of ears with
      otosclerosis. The volume of otosclerotic foci at the site anterior to the oval
      window region was less than 0.8 mm3 in 5 out of 7 ears. CONCLUSION: The incidence
      of histologic otosclerosis among Japanese seemed to be almost the same as that
      among Caucasians. Three reasons why clinical otosclerosis was not as prevalent
      among Japanese as among Caucasians are suggested: low incidence of involvement of
      foci anterior to the oval window, low activity, and small lesion without
      involvement of the footplate and/or membranous labyrinth of the inner ear.

PMID- 12806288
TI  - The effect of diabetes on sensorineural hearing loss.
AB  - OBJECTIVE: To identify whether patients with diabetes have a higher incidence of
      sensorineural hearing loss than the general population and examine whether
      control of diabetes is related to severity of hearing loss. STUDY DESIGN:
      Retrospective database review; complete data mining of electronic medical record
      from 1989 to present. SETTING: Tertiary referral center. PATIENTS: Electronic
      medical records from 53461 nondiabetic age-matched patients and 12575 diabetic
      patients were reviewed. MAIN OUTCOME MEASURES: Presence or absence of diabetes
      and/or sensorineural hearing loss, serum creatinine, pure tone hearing (dB),
      speech discrimination (%), serum cholesterol, and triglycerides. RESULTS:
      Sensorineural hearing loss was more common in the diabetic patients than in
      age0matched nondiabetic patients from the same institutions. Poor control of
      diabetes, as measured by increasing serum creatinine, but not apparent in
      hemoglobin A1C laboratory data, correlated with worsening hearing in patients
      with diabetes who had sensorineural hearing loss. CONCLUSIONS: Sensorineural
      hearing loss was more common in patients with diabetes than in the control
      nondiabetic patients, and severity of hearing loss seemed to correlate with
      progression of disease as reflected in serum creatinine. This may have been due
      to microangiopathic disease in the inner ear.

PMID- 12806289
TI  - Is there a relation between acoustic trauma or noise-induced hearing loss and a
      subsequent appearance of Meniere's Disease? An epidemiologic study of 17245 cases
      and a review of the literature.
AB  - OBJECTIVE: To explore whether acute acoustic trauma or noise-induced hearing loss
      may cause the later development of Meniere's Disease. STUDY DESIGN: Retrospective
      search of a military medical data bank. SETTING: Medical records of 17245 Israel
      Defense Force veterans who were recognized as being disabled as a result of
      acoustic trauma or noise-induced hearing loss. PATIENTS: Eleven cases of late
      onset Meniere's Disease were retrieved from these files. MAIN OUTCOME MEASURES:
      Documented symptoms and audiograms. RESULTS: Eleven of the 17425 veterans
      appeared to have typical Meniere's Disease. Their symptoms included attacks of
      vertigo, lasting between half an hour and a few hours and no more than 24 hours;
      the sensation of aural fullness; and tinnitus accompanied by a fluctuating or
      permanent low-tone hearing loss. Four of the 11 patients had a documented
      previous noise-induced hearing loss, and the remaining 7 had experienced acute
      acoustic trauma. The Meniere's Disease was bilateral in three cases. The average
      period between the first documented hearing loss and the onset of Meniere's
      Disease was 15.8 years (standard deviation, +/- 6.6 years). This yielded a
      prevalence of 1.9:100000 of Meniere's Disease in a population with acoustic
      trauma or noise-induced hearing loss-a figure comparable to that in the general
      population. CONCLUSIONS: No support was found for the hypothesis that Meniere's
      Disease may be causally related to previous acoustic trauma or noise-induced
      hearing loss.

PMID- 12806290
TI  - Comparison of different speech coding strategies using a disability-based
      inventory and speech perception tests in quiet and in noise.
AB  - OBJECTIVE: Intraindividual comparison of two cochlear implant speech coding
      strategies implemented in the Nucleus 24M system (SPEAK versus ACE). Reasons for
      subjective preference were evaluated using a combination of speech perception
      scores and a disability-based inventory. STUDY DESIGN: Cross-over study with two
      groups of cochlear implant subjects, assigned to first receive ACE or SPEAK
      strategy. SETTING: Cochlear implant program. SUBJECTS: Twelve postlingually deaf
      adults using a Nucleus 24M cochlear implant system. INTERVENTION: Subjects
      consecutively used the two different speech coding strategies and completed
      speech perception tests in quiet and in noise and a disability-based inventory
      (Abbreviated Profile of Hearing Aid Benefit). MAIN OUTCOME MEASURES: Individual
      differences between the two different speech coding strategies and the relation
      with subjective strategy preference. RESULTS: The ACE strategy produced somewhat
      better speech recognition scores in quiet and in noise, although the difference
      in the scores in noise did not reach the 95% level of significance. The first
      coding strategy chosen did not affect the results or subjective preference.
      Preference according to the APHAB results were not a priori in conformity with
      the speech recognition scores. CONCLUSION: Most subjects preferred the ACE
      strategy. Subjective preference was in agreement with the APHAB results in three
      subjects, in agreement with speech recognition in two subjects, and in agreement
      with both in seven subjects. The present results support the use of both speech
      recognition tests and questionnaires to evaluate different speech coding
      strategies.

PMID- 12806292
TI  - External auditory canal closure in cochlear implant surgery.
AB  - OBJECTIVE: To evaluate surgical techniques and complications associated with
      external auditory canal (EAC) closure in cochlear implant surgery. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral center with a large
      cochlear implant program. PATIENTS: Twenty-eight patients (8 adults and 20
      children) underwent multichannel cochlear implantation with EAC closure. The
      follow-up periods ranged between 1 and 10 years. Closure of the EAC was performed
      in conjunction with implantation of ears with chronic suppurative otitis media or
      cochlear drill-out procedures for ossification, or for access to the cochlea in
      patients with abnormal temporal bone anatomy. A modified Rambo technique was used
      for EAC closure in all but one case. INTERVENTIONS: Cochlear implantation with
      EAC closure and subsequent clinical and radiologic follow-up. MAIN OUTCOME
      MEASURES: Postoperative complications or the development of cholesteatoma in the
      implanted ear. RESULTS: Cholesteatoma developed in the implanted ear in two
      patients. Breakdown of EAC closure occurred in one of these patients. The details
      of these patients are reviewed. CONCLUSION: Closure of EAC can be done with
      relatively low risk. Close and careful follow-up is required for early detection
      of a developing cholesteatoma.

PMID- 12806291
TI  - Cochlear implantation in patients with bilateral Meniere's syndrome.
AB  - OBJECTIVE: To evaluate the indications and clinical outcomes (audiologic and
      vestibular) in patients with Meniere's syndrome who have undergone cochlear
      implantation. STUDY DESIGN: This is a retrospective review of patients at a large
      tertiary academic medical center. PATIENTS: Nine patients were included in the
      study with AAO-HNS criteria for diagnosis of Meniere's syndrome as well as
      bilateral severe to profound sensorineural hearing loss as an indication for
      undergoing cochlear implantation. Audiologic criteria for implantation were
      considered in the context of speech recognition performance with well-fit,
      powerful hearing aids noting large fluctuations in performance levels in some
      patients. In all cases, the poorer hearing ear was implanted. Seven subjects had
      bilateral disease and had progressed to profound sensorineural hearing loss. The
      average age of the patients was 61 years. Six patients had undergone previous
      surgery to control vertigo, including endolymphatic shunt surgery and vestibular
      nerve section. No patient had received previous treatment with intra-tympanic
      gentamicin. Symptoms of Meniere's syndrome had been present in all patients for
      at least 10 years before implantation. INTERVENTION: Cochlear Implantation. MAIN
      OUTCOME MEASURES: Pre- and Postoperative audiometric scores (monosyllable
      words/phonemes, Central Institute for the Deaf (CID) sentences, Hearing in Noise
      Test (HINT) in quite/noise (+10 db)), pre- and postoperative vestibular symptoms
      (number of vestibular attacks, aural fullness, tinnitus). RESULTS: Follow-up
      after implantation ranged from 1 to 5 years. Average 6 month postimplantation
      scores were: monosyllable words/phonemes = 52%/65%, CID sentences = 82%, HINT in
      quiet/noise = 70%/50%. Average 1-year postimplant scores were: monosyllable
      words/phonemes = 60%/76%, CID sentences = 97%, HINT in quiet/noise = 89%/78%.
      Postoperative speech recognition scores were, on average, substantially greater
      than preoperative scores. While there were few complications associated with
      implantation, some patients experienced alterations in their implant performance
      in association with fluctuations in vestibular symptoms. CONCLUSIONS: Patients
      with advanced binaural involvement with Meniere's Disease may present a challenge
      to conventional criteria for cochlear implant candidacy because of fluctuating
      symptoms. We observed significant benefit over baseline in a consecutive series
      of patients with Meniere's syndrome who progressed to bilateral, severe-to
      profound sensorineural hearing loss and underwent cochlear implantation. Further,
      previous vestibular surgery, including labyrinthectomy, does not contraindicate
      cochlear implantation.

PMID- 12806293
TI  - Arrest of apoptosis in auditory neurons: implications for sensorineural
      preservation in cochlear implantation.
AB  - HYPOTHESIS: The JNK/c-Jun cell death pathway is a major pathway responsible for
      the loss of oxidative stress-damaged auditory neurons. BACKGROUND: Implantation
      of patients with residual hearing accentuates the need to preserve functioning
      sensorineural elements. Although some auditory function may survive electrode
      insertion, the probability of initiating an ongoing loss of auditory neurons and
      hair cells is unknown. Cochlear implantation can potentially generate oxidative
      stress, which can initiate the cell death of both auditory neurons and hair
      cells. METHODS: Dissociated cell cultures of P4 rat auditory neurons identified
      the apoptotic pathway initiated by oxidative stress insults (e.g., loss of
      trophic factor support) and characterized this pathway by arresting translation
      of pathway-specific mRNA with antisense oligonucleotide treatment and with the
      use of pathway specific inhibitors. The presence or absence of apoptosis-specific
      protein and changes in the level of neuronal survival measured the efficacy of
      these interventional strategies. RESULTS: These in vitro studies identified the
      JNK/c-Jun cascade as a major initiator of apoptosis of auditory neurons in
      response to oxidative stress. Neurons pretreated with c-jun antisense
      oligonucleotide and exposed to high levels of oxidative stress were rescued from
      apoptosis, whereas neurons in treatment control cultures died. Treatment of
      oxidative-stressed cultures with either curcumin, a MAPKKK pathway inhibitor, or
      PD-098059, a MEK1 inhibitor, blocked loss of neurons via the JNK/c-Jun apoptotic
      pathway. CONCLUSION: Blocking the JNK/c-Jun cell death pathway is a feasible
      approach to treating oxidative stress-induced apoptosis within the cochlea and
      may have application as an otoprotective strategy during cochlear implantation.

PMID- 12806294
TI  - A review of cochlear implantation in mitochondrial sensorineural hearing loss.
AB  - OBJECTIVE: Mitochondrial sensorineural hearing loss (SNHL) may be nonsyndromic
      (occurring in isolation), associated with the A1555G mutation in the MTRNR1 gene.
      Mitochondrial SNHL may also be syndromic, associated with the A3243G point
      mutation in the MTTL1 gene. In syndromic cases-mitochondrial encephalopathy,
      lactic acidosis, and strokelike episodes (MELAS), maternally inherited diabetes
      and deafness, Kearns-Sayre syndrome, and chronic progressive external
      ophthalmoplegia-the SNHL compounds already existing disabilities. The genetic
      basis for mitochondrial SNHL and postulated sites of pathologic changes are
      discussed. DATA SOURCES: Sources used were relevant clinical and basic science
      publications. STUDY SELECTION: A search of the entire databases of Medline and
      Web of Science, using various subject headings and free-text terms, was used to
      identify patients with mitochondrial disease having cochlear implants. DATA
      EXTRACTION: The data from publications were critically reviewed and tabulated to
      assess implantation outcomes. DATA SYNTHESIS: The data were not amenable to
      formal meta-analysis or valid data summarization, other than descriptive
      statistics. CONCLUSIONS: There is an increasing awareness of the prevalence of
      mitochondrial SNHL and its progressive nature. High-risk candidates warrant
      genetic testing and family screening. Correlating the data for mitochondrial SNHL
      as a treatable entity is important, and the authors present an overview of these
      patients successfully rehabilitated by cochlear implantation.

PMID- 12806295
TI  - A middle ear implant, the Symphonix Vibrant Soundbridge: retrospective study of
      the first 125 patients implanted in France.
AB  - OBJECTIVE: The Vibrant Soundbridge is an active semi-implantable middle ear
      implant for the rehabilitation of patients with a sensorineural hearing loss who
      are not able to derive adequate benefit from conventional hearing aids. A
      retrospective study was performed to assess the overall level of satisfaction of
      implanted patients and to investigate the potential determinants of postoperative
      success. STUDY DESIGN: A retrospective survey of audiological data from repeated
      measures and subjective data from self-assessment scales administered
      postoperatively was conducted to determine the degree of benefit and satisfaction
      for Vibrant Soundbridge implantees. SETTING: Twenty-one tertiary referral and
      teaching hospitals. SUBJECTS: The first 125 VSB implantees implanted in France
      between August 1997 and May 2001 were included in the study. RESULTS: No
      clinically significant change was observed for residual hearing postoperatively.
      Most patients (83%) reported they were either satisfied or very satisfied with
      the Vibrant Soundbridge. Analysis of correlation revealed a moderate correlation
      (Pearson coefficient r = 0.59) between the degree of benefit reported via the
      patient survey and the degree of benefit reported via the Glasgow Benefit
      Inventory. A moderate correlation (Pearson coefficient r = 0.66) was observed
      between speech comprehension scores in quiet for the preoperative unaided
      condition and the postoperative aided Vibrant Soundbridge condition. No
      correlation was observed between subjective reports of satisfaction
      postoperatively and performance on preoperative objective tests or patient
      characteristics. CONCLUSION: The results indicate a high level of satisfaction
      with the VSB as a treatment of sensorineural hearing impairment in patients with
      a wide range of characteristics. Preoperative scores for unaided speech
      comprehension tests in quiet may be a potential indicator of success on aided
      Vibrant Soundbridge speech comprehension tests postoperatively but do not reflect
      patient satisfaction with the device reported on self-assessment scales.

PMID- 12806296
TI  - Congenital aplasia of the semicircular canals.
AB  - OBJECTIVE: To describe the underrecognized inner ear malformation characterized
      by complete aplasia of the labyrinthine semicircular canals associated with a
      relatively well-formed cochlea, to investigate its relationship with known
      syndromic forms of hearing loss, and to hypothesize regarding the potential
      embryopathogenesis of this anomaly. STUDY DESIGN: A retrospective case review
      consisting of cases of sensorineural hearing loss with radiographic evidence
      demonstrating agenesis of the semicircular canals associated with a cochlea that
      was either morphologically normal or sufficiently well developed to accommodate
      the full insertion of a cochlear implant electrode. Cases were identified by
      computerized tomography findings that identified the anomaly under study.
      SETTING: Departments of otolaryngology and radiology in a tertiary referral
      center, with a large cochlear implant program serving over 800 patients, more
      than half of whom are children. PATIENTS: Fifteen patients with the anomaly under
      study were identified. INTERVENTIONS: Each patient underwent a complete otologic
      examination, audiometric studies, and high resolution computerized tomography of
      the temporal bone in axial and coronal planes. MAIN OUTCOME MEASURES: The bony
      morphology of the cochlea, round and oval windows, vestibule, semicircular
      canals, and vestibular aqueduct, and the course of the facial nerve were
      examined. Auditory findings and otologic treatment are presented. RESULTS: Of the
      15 identified patients, 4 were nonsyndromic, 9 had CHARGE association (Coloboma
      of the eye, congenital Heart defects, choanal Atresia, mental and/or growth
      Retardation, Genital hypoplasia, and Ear anomalies and/or deafness), 1 met
      criteria for Noonan's syndrome, and one had features of both these syndromes.
      Although the cochlea was present in all cases, the cochlear morphology was
      usually abnormal in the CHARGE association patients. Of the 20 ears in the CHARGE
      subjects, only 3 ears (15%) were seen to have completely normal development of
      the cochlea in both the basal and upper turns. The others showed either mild
      hypoplasia of the upper turns (13 ears, 65%) or an incomplete partition typical
      of the classic Mondini deformity (4 ears, 20%). In the 4 nonsyndromic cases, one
      subject had bilateral Mondini dysplasia and the other three had normal cochleae.
      In the entire group, abnormalities of oval window development were common (20 of
      30 ears, 67%), especially in the syndromic cases (18/22, 81%), but the round
      window was normal in the majority of cases (73%). Seven patients in the CHARGE
      association group had an anomalous course of the facial nerve, which was
      particularly severe in three. Four patients had congenital unilateral facial
      paralysis, although two of these children had normal radiographic anatomy of the
      facial nerve. One patient had bilateral facial weakness. CONCLUSIONS: Syndromic
      and nonsyndromic cases of isolated semicircular canal aplasia were identified.
      Except for mild to moderate cochlear dysplasia, and the anomalous course of the
      facial nerve in some CHARGE association patients, both groups of patients were
      generally suitable for cochlear implantation if indicated. A high incidence of
      oval window aplasia with normal round window development may help to explain the
      embryopathogenesis of this anomaly, considering the sequence of inner ear
      development.

PMID- 12806297
TI  - Topical ofloxacin for chronic suppurative otitis media and acute exacerbation of
      chronic otitis media: optimum duration of treatment.
AB  - OBJECTIVE: To assess the optimum duration of topical ofloxacin therapy for
      chronic otitis media and to compare the response between patients with chronic
      suppurative otitis media (CSOM) and acute exacerbation of chronic otitis media
      (AE). STUDY DESIGN: Prospective observational study. SETTING: Five university
      hospitals and 30 affiliated institutions. PATIENTS: A total of 294 patients who
      presented to the participating institutions with CSOM were enrolled. Among them,
      268 patients were evaluable for safety and 237 were evaluable for efficacy (64
      with CSOM and 173 with AE . INTERVENTION: Ofloxacin otic solution was
      administered for as long as 4 weeks. MAIN OUTCOME MEASURES: Clinical and
      bacteriologic assessment was done weekly during the treatment period. The
      clinical response was assessed on the basis of the symptom scores. RESULTS: There
      were no differences between CSOM and AE patients with respect to sex, age, and
      severity. The most common bacterial isolate from middle ear discharge was
      Staphylococcus aureus. The clinical response rates in patients with CSOM and AE
      were 39.1% and 61.3% after 2 weeks of treatment and 57.8% and 75.1% after 4
      weeks, respectively, and the bacterial eradication rate was 91.0% at 2 weeks and
      94.6% at 4 weeks. Detection of new fungal infection did not increase as the
      duration of therapy was prolonged. No serious adverse events were reported.
      CONCLUSIONS: The duration of treatment was shorter and the clinical response was
      higher in AE patients than in CSOM patients. The standard topical ofloxacin
      regimen for chronic otitis media should consist of a 2-week course from the
      aspect of bacteriologic efficacy, although patients showing insufficient
      symptomatic improvement after 2 weeks may benefit from another 1 or 2 weeks of
      therapy. Administration of this drug for as long as 4 weeks can increase the
      clinical efficacy without causing safety problems.

PMID- 12806298
TI  - Hearing outcome after concurrent endolymphatic shunt and vestibular nerve
      section.
AB  - OBJECTIVE: To determine if endolymphatic shunt surgery concurrent with vestibular
      nerve section improves hearing outcome compared with vestibular nerve section
      alone. STUDY DESIGN: Retrospective observational study with cross-sectional
      survey. SETTING: Tertiary otologic private practice. PATIENTS: Thirty-five
      patients who underwent vestibular nerve section and endolymphatic shunt surgery
      and 17 patients who had vestibular nerve section alone between 1985 and 2000.
      METHODS: Chart review and correspondence for audiogram results and survey. MAIN
      OUTCOME MEASURES: Hearing at last follow-up. Hearing Handicap Inventory,
      Dizziness Handicap Inventory, Tinnitus Handicap Inventory, and SF-36. RESULTS:
      Eight patients in the vestibular nerve section and 15 in the vestibular nerve
      section and endolymphatic shunt surgery group had an audiogram at more than 16
      months after surgery available for review. In the vestibular nerve section group,
      three patients had same hearing whereas five were worse. In the vestibular nerve
      section and endolymphatic shunt surgery group, 2 patients showed improvement, 2
      were the same, and 11 were worse. There was no significant difference in the
      change from preoperative pure tone average or Word Discrimination Score to
      postoperative levels between the surgical groups. Eighteen patients had
      serviceable hearing preoperatively. Five of 8 in the vestibular nerve section and
      4 of 10 in the vestibular nerve section and endolymphatic shunt surgery groups
      maintained serviceable hearing postoperatively. Of the 52 patients, 33 responded
      to the survey (63%). There were no significant differences between the groups for
      Dizziness Handicap Inventory, Hearing Handicap Inventory, Tinnitus Handicap
      Inventory, or SF-36, suggesting that patient-oriented outcomes are the same in
      both groups. CONCLUSIONS: Concurrent endolymphatic shunt surgery and vestibular
      nerve section does not improve hearing or tinnitus outcome over vestibular nerve
      section alone.

PMID- 12806299
TI  - Is it worthwhile to attempt hearing preservation in larger acoustic neuromas?
AB  - OBJECTIVE: To determine the hearing outcome in patients undergoing surgery via
      the retrosigmoid approach for acoustic neuromas with a substantial component in
      the cerebellopontine angle. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: The medical records of all patients
      undergoing acoustic neuroma removal via the retrosigmoid approach at a tertiary
      referral center were retrospectively reviewed. Sixty-four patients with both
      cerebellopontine angle component >or=15 mm and preoperative audiometry of class A
      or B (American Academy of Otolaryngology-Head and Neck Surgery) were identified.
      MAIN OUTCOME MEASURES: Postoperative average pure tone threshold and word
      recognition scores, categorized according to the classification of the American
      Academy of Otolaryngology-Head and Neck Surgery, were used to assess hearing
      outcome. RESULTS: Overall, only 6.3% (4 of 63) retained good hearing (class A or
      B) postoperatively. Hearing preservation rate in the smallest (15- to 19-mm)
      group was 17.6% (3 of 17), which was better than that for the larger groups. No
      successful hearing preservation was achieved in tumors with >or=25 mm
      cerebellopontine angle component (0 of 23). CONCLUSIONS: Surgeon and patient
      alike would always choose a hearing preservation technique if there was no
      potential for increased morbidity in making the attempt. When compared with the
      non-hearing preservation translabyrinthine approach, the retrosigmoid approach
      had a higher incidence of persistent headache. In addition, efforts to conserve
      the auditory nerve prolong operating time, increase the incidence of
      postoperative vestibular dysfunction, and carry a slightly higher risk of tumor
      recurrence. Nevertheless, even though the probability of success is
      disappointingly small, when excellent hearing is present we favor offering the
      option of a hearing conservation attempt when the patient has been well informed
      of the pros and cons of the endeavor. Factors weighing against undertaking this
      effort include larger cerebellopontine angle component (>or=25 mm), deep
      involvement of the fundus, wide erosion of the porus, and marginal residual
      hearing.

PMID- 12806300
TI  - The efficacy of corticosteroids in restoring hearing in patients undergoing
      conservative management of acoustic neuromas.
AB  - OBJECTIVE: To evaluate the role of corticosteroids in restoring hearing in
      patients undergoing conservative management of acoustic neuromas. STUDY DESIGN:
      Prospective cohort. SETTING: Tertiary referral center. PATIENTS: Seven patients
      with acute hearing loss secondary to an acoustic neuroma. INTERVENTION: Oral
      prednisone (1 mg/kg for 1 to 2 weeks) within a week of onset of hearing loss.
      MAIN OUTCOME MEASURES: Audiometric assessment at the time of presentation and
      after corticosteroid therapy. RESULTS: All seven patients had pure tone reception
      threshold improvements ranging from 10 to 50 dB in at least two frequencies or
      more. Speech discrimination thresholds improved after therapy in all seven
      patients, with gains of 4 to 38% points. CONCLUSIONS: Patients with acoustic
      neuromas who are being treated with a "watchful waiting" approach should receive
      corticosteroid treatment at the first signs of hearing deterioration. An
      evaluation to rule out a retrocochlear lesion is mandated in patients with sudden
      hearing loss, regardless of whether the hearing loss responds to corticosteroid
      treatment. Older data documenting the efficacy of corticosteroids in the
      treatment of sudden hearing loss may need to be reevaluated, given that many of
      these studies were conducted before MRI was available.

PMID- 12806301
TI  - Cerebellopontine angle paraganglioma.
AB  - BACKGROUND: Acoustic neuroma account for 80% of cerebellopontine angle tumors.
      Paraganglioma is a rare tumor in this region. OBJECTIVE: The authors report a
      case of cerebellopontine angle paraganglioma arising from the anterior inferior
      cerebellar artery. RESULTS: The clinical and radiologic features were
      indistinguishable from those of a neuroma, and only the intraoperative view
      showed a vascular tumor. Definitive diagnosis was made by histopathologic
      methods. CONCLUSIONS: This unique paraganglioma location may be explained by
      existing embryologic data. The minimal retrosigmoid approach, assisted by
      endoscopy, allows safe and complete removal of the tumor.

PMID- 12806302
TI  - The effect of age on acoustic neuroma surgery outcomes.
AB  - OBJECTIVES: To ascertain the effect of age on hearing preservation, facial nerve
      outcome, and complication rates after acoustic neuroma surgery. STUDY DESIGN:
      Retrospective chart review. Two study arms were used: a comparison of the
      authors' oldest patients with their youngest patients (extremes of age arm) and
      an analysis of all middle fossa surgical procedures (middle fossa arm). SETTING:
      Tertiary referral center PATIENTS: Total of 329 patients. For the extremes of age
      arm, 205 patients were studied in two cohorts with 150 older patients (>60 years)
      compared with 55 younger patients (<40 years). The approaches included 21 middle
      fossa (MF), 38 retrosigmoid (RS), and 91 translabyrinthine (TL) procedures in the
      older group versus 25 MF, 17 RS, and 13 TL in the younger. For the middle fossa
      arm, there were 170 patients (age range 15-76 years) who underwent the MF
      approach for an attempt at hearing preservation. MAIN OUTCOME MEASURES: Hearing
      preservation was defined as the maintenance of either class A or class B hearing
      (AAO-HNS class). Good facial nerve outcome was considered the maintenance of
      either grade 1 or 2 (House-Brackmann scale). Cerebrospinal fluid leak rates and
      other postoperative complications were also tabulated. RESULTS: After adjustment
      for tumor size and surgical approach using multiple logistic regression analysis,
      the extremes of age study arm demonstrated that there is a lower chance of
      preserving good hearing in older patients (p = 0.048, odds ratio = 0.30). Age was
      not associated with a difference in the rate of good facial nerve outcome (p =
      0.2). There was a trend toward slightly higher rates of cerebrospinal fluid leak
      in the older patient group (p = 0.07) but no difference in the rate of other
      complications (p = 0.9). The middle fossa study arm, after adjustment for tumor
      size and surgical approach, demonstrated that older patient age is associated
      with a lower rate of preservation of good hearing (p = 0.01, O.R.=1.044). There
      was no association between age and good facial outcome (p = 0.7). CONCLUSIONS:
      Older patient age lowers the chance of hearing preservation but does not affect
      facial outcomes. There is a trend toward a higher rate of cerebrospinal fluid
      leak in older patients, but no increased risk of other complications.

PMID- 12806303
TI  - Electrical suppression of tinnitus with high-rate pulse trains.
AB  - HYPOTHESIS: Application of high-rate pulse trains (e.g., 4800 pps) to the cochlea
      may represent an effective treatment of tinnitus. BACKGROUND: Tinnitus is a
      widespread clinical problem with multiple treatments but no cure. A cure for
      tinnitus would restore the perception of silence. One plausible hypothesis for
      the origin of tinnitus associated with sensorineural hearing loss is that it is
      due to loss or alteration of the normal spontaneous activity in the deafferented
      regions of the cochlea. Electrical stimulation of the cochlea with 5000-pps pulse
      trains can produce spontaneous-like patterns of spike activity in the auditory
      nerve. METHODS: Eleven volunteer human subjects with bothersome tinnitus and high
      frequency sensorineural hearing loss underwent myringotomy and temporary
      placement of a round window electrode. High-rate pulse train stimuli were
      presented at various stimulus intensities and tinnitus, and stimulus perception
      were scaled by the subject. Three cochlear implant recipients with tinnitus in
      the implanted ear underwent similar stimulation. RESULTS: Five of 11 (45%) of
      transtympanic subjects showed substantial or complete tinnitus suppression with
      either no perception or only a transient perception of the stimulus. Three showed
      tinnitus suppression only in association with the perception of the stimulus.
      Three showed no effects on tinnitus. A similar pattern of responses was seen in
      the cochlear implant subjects. CONCLUSIONS: Although the study lacked an ideal
      placebo control, the results are promising and support further research to
      develop a clinically useful intervention for this troubling disorder.

PMID- 12806305
TI  - Epineurial pseudocysts of the intratemporal facial nerve.
AB  - OBJECTIVE: Facial nerve pseudocysts are infrequently encountered during temporal
      bone surgery or neurotologic evaluation. This report describes the senior
      author's experience with epineurial pseudocysts of the intratemporal facial
      nerve. STUDY DESIGN: Retrospective case review. SETTING: Academic, tertiary
      referral center. RESULTS: Epineurial pseudocysts were identified on computed
      tomography in the mastoid segment in seven patients during evaluation for
      profound sensorineural hearing loss or facial nerve symptoms. Histopathologic
      examination revealed fibroadipose tissue without nerve tissue in five cases that
      underwent excision. CONCLUSIONS: Facial nerve epineurial pseudocysts are
      uncommon, benign lesions of the mastoid segment. Surgical excision may be safely
      performed for facial motor symptoms or for cochlear implant placement.

PMID- 12806304
TI  - Facial nerve grafting.
AB  - OBJECTIVE: To evaluate the results of facial nerve reconstruction by means of
      grafting and to determine the influence of different variables on final
      functional recovery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      otologic and skull base referral center. PATIENTS: Sixty nine patients underwent
      facial nerve grafting. Facial nerve tumors (24) or vestibular schwannomas (18)
      affected most of them. Preoperatively, 47 patients had a clinical facial nerve
      deficit lasting from 1 to 120 months, with a mean of 20.2 months. MAIN OUTCOME
      MEASURES: Final facial nerve motor function. RESULTS: Among the 56 patients with
      a follow-up time equal to or longer than 1 year, 26 recovered to a Grade III
      (46.4%), 14 to a Grade IV (25%), while 16 remained at Grade V or Grade VI
      according to the House-Brackmann scale. Patients with a preoperative facial nerve
      deficit for more than 1 year showed the lowest rate of recovery, with only 3
      cases (19%) reaching Grade III. CONCLUSIONS: Duration of the preoperative facial
      nerve deficit emerged as the most important factor influencing final results.
      According to the authors' data, the 1-year period after the occurrence of the
      preoperative clinical deficit seemed to be the cutoff point in achieving a high
      rate of good postoperative recovery. Among the other factors that might have
      influenced the final outcome, only the underlying cause of the lesion played a
      significant role.

PMID- 12806306
TI  - Tympanic membrane vessel revisited: a study in an animal model.
AB  - HYPOTHESIS: The present study aimed at elucidating whether there are blood
      vessels in the semitransparent portion of the tympanic membrane. BACKGROUND: The
      normal semitransparent portions of pars tensa show strikingly few, small-caliber
      vessels under the otomicroscope. The major portion of a pars tensa seems to be
      devoid of blood vessels. In inflammatory conditions of the middle ear, the
      vascular pattern of the tympanic membrane is dramatically altered, and blood
      vessels traversing the pars tensa can be discernable. METHODS: The study was
      performed in rats with healthy tympanic membranes and in tympanic membranes
      obtained from animals with purulent otitis media evoked by inoculation of Str.
      pneumoniae. The tympanic membrane vessels were dilated by injection of adenosin,
      and directly afterwards the animal was perfused with china ink. Vessels were also
      revealed by immunohistochemistry with antibodies for Thy-1 and the von Willebrand
      factor as well as by detection of carbon particles at an ultrastructural level.
      RESULTS: Adenosin caused a marked dilation of the mallear and annular vessels.
      However, no preexisting vasculature was revealed in the normally transparent
      portions of the pars tensa except single vessels in the posterior quadrant and in
      the lower quadrants. In Str. pneumoniae-induced acute otitis media, the tympanic
      membrane thickened, bulged, and discolored. Even then, at 12 hours after
      inoculation, no vessels could be distinguished in the normally transparent
      portions of the tympanic membrane. However, at 4 and 7 days of acute purulent
      otitis media, vessels developed in those areas, most probably through ingrowth of
      newly formed vessels. CONCLUSION: The results support the view that the
      semitransparent portions of the pars tensa lack vascularity. In inflammation, new
      vessels are formed in pars tensa to meet the demand for an increased blood
      supply.

PMID- 12806307
TI  - Djourno, Eyries, and the first implanted electrical neural stimulator to restore
      hearing.

PMID- 12806308
TI  - The artificial tympanic membrane (1840-1910): from brilliant innovation to quack
      device.
AB  - OBJECTIVE: To present the rich and checkered history of the artificial eardrum, a
      widely used device in the 19th century, and to illustrate the behavior of
      otologists in response to the introduction of a promising new technology. DATA
      SOURCES: Over 40 published books and articles spanning the years 1821 to 1909 in
      English, German, and French. DEVICE DESCRIPTIONS: A wide variety of devices were
      used to improve hearing and, purportedly, to reduce aural discharge. The most
      popular devices were made of gutta percha attached to a silver wire stem
      (Toynbee) and cotton balls with extraction cords (Yearsley). Other membranes
      included India rubber, lint, tin or silver foil, and even the vitelline membrane
      of an egg. Adhesion to the drum remnant was with saliva, water, petroleum jelly
      (Vaseline), or glycerin. Some were applied by the physician, whereas others were
      inserted daily by the patient, much as contact lenses are today. CONCLUSIONS: In
      several cases, the method of positioning an object over the drum remnant was
      actually invented by clever patients and then later adopted by practitioners.
      Once introduced, great optimism was generated about the "miraculous" value of
      this deafness cure. Petty jealousy among early inventors led to very public (and
      unprofessional) quarrels over the primacy of invention and bickering about whose
      device was superior. Over the subsequent decades, as more experience demonstrated
      the device's limited value, enthusiasm waned until otologists largely abandoned
      these devices around the turn of the last century. In the first two decades of
      the 20th century, artificial eardrums reached their peak of fame among the public
      when they were enthusiastically (and dishonestly) marketed by numerous quacks
      through newspaper advertisements as a universal cure for all forms of deafness.
      Only with the coming of the Food and Drug Administration did advertisements for
      US dollars 5 mail-order, medicated eardrums disappear from popular newspapers and
      magazines.

PMID- 12806309
TI  - Malleus handle fracture.

PMID- 12806310
TI  - Temporal bone fracture and latent meningitis: temporal bone histopathology study
      of the month.

PMID- 12806311
TI  - The strong relation between Yanagihara's scores and electroneurography in the
      acute stage of bell's palsy.

PMID- 12806312
TI  - Exocytosis of the external auditory canal.

PMID- 12806314
TI  - Pathogenesis and clinical physiology of hypertension.

PMID- 12806313
TI  - Cerebro-spinal fluid leak after acoustic neuroma surgery.

PMID- 12806315
TI  - The heart, kidney, and brain as target organs in hypertension.

PMID- 12806316
TI  - Hypertension in special populations.

PMID- 12806317
TI  - The continuing reduction of the residual alveolar ridges in complete denture
      wearers: a mixed-longitudinal study covering 25 years. 1972.

PMID- 12806318
TI  - Implant prosthodontic rehabilitation of a patient with nevoid basal cell
      carcinoma syndrome: a clinical report.
AB  - This clinical report describes the prosthodontic rehabilitation of an edentulous
      patient with compromised maxillary and mandibular anatomy, caused by the
      resection of several odontogenic keratocysts associated with nevoid basal cell
      carcinoma syndrome. Preprosthetic surgical preparation included iliac crest bone
      grafting to both arches and placement of implants. Prosthodontic treatment
      included the fabrication of maxillary and mandibular dental implant-supported
      connecting bars and construction of attachment-retained overdentures.

PMID- 12806319
TI  - Inlay fixed partial denture as a conservative approach for restoring posterior
      missing teeth: a clinical report.
AB  - Inlay fixed partial dentures luted by use of adhesive procedures offer a clinical
      alternative for the restoration of single missing posterior teeth. The
      introduction of ceromers and fiber-reinforced composites and the continuous
      improvement of adhesive systems and luting agents make this type of restoration
      possible, offering good aesthetic and functional results. The procedure is
      minimally invasive and conservative. This clinical report reviews the factors
      influencing the diagnosis and the clinical indications for an inlay fixed partial
      denture. In addition, a patient treatment is presented to illustrate the clinical
      procedures involved.

PMID- 12806320
TI  - Magnet-retained auricular prosthesis with an implant-supported composite bar: a
      clinical report.
AB  - The use of craniofacial implants to assist in retaining auricular prostheses
      often requires complex laboratory procedures, involving production of an accurate
      casting, fitting of a precious alloy bar, and the use of clips. A simplified
      method for the retention of an auricular prosthesis with a composite bar and
      magnets is described in this article.

PMID- 12806321
TI  - Rhinorrhea induced by loading of dental implants supporting an obturator
      prosthesis: a clinical report.
AB  - This clinical report describes an unusual situation of nasal discharge that was
      initially considered to be caused by a leaking obturator prosthesis in a
      partially repaired cleft palate patient. Ultimately, the diagnosis was rhinorrhea
      induced by the loading of dental implants that supported the obturator. The
      differential diagnoses of nasal irritation, blocking of nasal drainage posterior
      or anterior through a premaxillary defect, vasomotor rhinitis, and gustatory
      rhinorrhea are presented and discussed, as well as the measures taken to reach
      the final diagnosis.

PMID- 12806322
TI  - Anatomic crown width/length ratios of unworn and worn maxillary teeth in white
      subjects.
AB  - STATEMENT OF PROBLEM: Dimensions of teeth have been available for a century. Some
      significant and clinically relevant aspects of dental esthetics, however, such as
      the crown width/length ratios, have not been presented in tooth morphology
      sources until recently. PURPOSE: The purpose of this study was to analyze the
      anatomic crowns of 4 tooth groups (central incisors, lateral incisors, canines,
      and first premolars) of the maxillary dentition with respect to width, length and
      width/length ratios and determine how these parameters are influenced by the
      incisal edge wear. MATERIAL AND METHODS: Standardized digital images of 146
      extracted human maxillary anterior teeth from white subjects (44 central
      incisors, 41 lateral incisors, 38 canines, 23 first premolars) were used to
      measure the widest mesiodistal portion "W" (in millimeters) and the longest
      inciso-cervical/occluso-cervical distance "L" (in millimeters). The width/length
      ratio "R" (%) was calculated for each tooth. A 1-way analysis of variance was
      used to compare the mean values of W, L, and R for the different groups ("unworn"
      and "worn" subgroups, except for premolars). Multiple least significant
      difference range tests (confidence level 95%) were then applied to determine
      which means differed statistically from others. RESULTS: There was no influence
      of the incisal wear on the average value of W (width) within the same tooth
      group. The widest crowns were those of central incisors (9.10 to 9.24 mm) >
      canines (7.90 to 8.06 mm) > lateral incisors (7.07 to 7.38 mm). Premolars (7.84
      mm) had similar width as canines and worn lateral incisors. The L-value was
      logically influenced by incisal wear (worn teeth were shorter than unworn teeth)
      except for lateral incisors. The longest crowns were those of unworn central
      incisors (11.69 mm) > unworn canines (10.83 mm) and worn central incisors (10.67
      mm) > worn canines (9.90), worn and unworn lateral incisors (9.34 to 9.55 mm),
      and premolars (9.33 mm). Width/length ratios also showed significant differences.
      The highest values were found for worn central incisors (87%) and premolars
      (84%). The latter were also similar to worn canines (81%), which constituted a
      homogeneous group with worn lateral incisors (79%) and unworn central incisors
      (78%). The lowest ratios were found for unworn canines and unworn lateral
      incisors (both showing 73%). CONCLUSIONS: Along with other specific and objective
      parameters related to dental esthetics, average values for W (mesiodistal crown
      dimension), L (inciso-cervical crown dimension), and R (width/length ratio) given
      in this study for white subjects may serve as guidelines for treatment planning
      in restorative dentistry and periodontal surgery.

PMID- 12806323
TI  - Assessment of the resistance to fracture of endodontically treated molars
      restored with amalgam.
AB  - STATEMENT OF PROBLEM: Controversy exists concerning the preferred type of final
      restoration of endodontically treated molars regarding their resistance to
      fracture under occlusal load. PURPOSE: The aim of this study was to assess the
      resistance to fracture of endodontically treated molars with various degrees of
      tooth structure loss restored with amalgam under simulated occlusal load.
      MATERIAL AND METHODS: . The study teeth consisted of 90 noncarious, nonrestored
      molars stored in physiological saline solution. The teeth were endodontically
      treated and randomly divided into 9 experimental groups of 10 specimens each with
      various degrees of tooth loss, ranging from a conservative endodontic access to
      removal of all cusps. All teeth were restored with a standardized technique to
      their original contour with amalgam. Each specimen was mounted onto a specialized
      jig for loading at the central fossa at a 30-degree angle to the long tooth axis.
      The resistance to fracture, under continuous compressive force at a cross-head
      speed of 2 mm/minute, was applied by a universal testing machine and was
      recorded. One-way analysis of variance with Scheffe contrast was used to
      statistically compare the differences between the groups at significance level
      P<.05. RESULTS: One-way analysis of variance showed that the group with a
      conservative endodontic access (1137.6 +/- 311.6 N) and the group with removal of
      all cusps (1261.4 +/- 195.1 N) presented a significantly higher resistance to
      fracture when compared with the other groups (P<.05). There was no significant
      difference in resistance to fracture under the simulated load between the other 7
      groups, which ranged from 655.8 +/- 229.4 to 906.3 +/- 168.1 N (P>.05).
      CONCLUSION: Within the limitations of this study, the endodontically treated
      molars with a conservative endodontic access or after removal of all cusps that
      were restored to their original contour with amalgam presented the highest
      resistance to fracture under a simulated occlusal load.

PMID- 12806324
TI  - Effect of three bleaching agents on the surface properties of three different
      esthetic restorative materials.
AB  - STATEMENT OF PROBLEM: Information related to the effect of night-guard vital
      bleaching procedure on the surface properties of esthetic dental restorative
      materials is incomplete. PURPOSE: The aim of this study was to examine the
      effects of 3 proprietary carbamide peroxide bleaching agents on the surface
      properties of 3 dental esthetic restorative materials. MATERIAL AND METHODS:
      Three bleaching products (Nite White, Opalescence, and Rembrandt Lighten Gel) and
      3 restorative materials (Duceram, Fuji II LC, and Silux Plus) were studied. A
      stainless steel mold and a 6-mm-thick polytetrafluoroethylene plate with a 1-cm
      diameter hole were used to prepare 30 standardized specimens for each of the 3
      restorative materials tested. Each group was divided into 3 subgroups (n=10). Two
      specimens from each subgroup were selected to form a control group. Three
      different carbamide peroxide bleaching agents were applied to each restorative
      material group for 8 hours per day for 30 days, respectively. Initial roughness
      measurements (Ra measured in microm) were made by use of a profilometer, at
      repeated intervals of 24 hours, 48 hours, 1, 2, 3, and 4 weeks (30 days). Surface
      topography of the specimens was assessed by scanning electron microscopy, and
      results were compared with the control group graphically. Surface structure and
      alterations of atomic weight percentages of element were made by use of energy
      dispersive x-ray microanalysis. One-way analysis of variance was used to evaluate
      the surface roughness measurements. Significant results were evaluated with
      Fisher and Duncan's multiple range test (P<.005) RESULT: Surface roughness values
      for all restorative materials increased during the bleaching procedure. The only
      significant increase was found with the effect of Rembrandt bleaching gel on
      modified glass ionomer cement (mean Ra was 0.48 microm initially, 0.5 microm at
      24 hours, 0.75 microm at 2 weeks, and 0.83 microm at 30 days). Surface roughness
      values increased significantly during the first 2 weeks (P<.005) for all
      bleaching groups of each restorative material, and no significant changes were
      seen in the following periods. SEM micrographs of the feldspathic porcelain
      specimens for each bleaching agent appeared to be similar to the control group.
      All of the modified glass ionomer specimens revealed serious cracking areas,
      whereas microfilled composite specimens showed increased surface porosity and
      cracks in certain areas when compared with control specimens. Surface spectral
      analyses results indicated a decrease in the SiO(2) content in the feldspathic
      porcelain and the microfilled composite groups for all bleaching agents. Modified
      glass ionomer specimens bleached with Nite White and Rembrandt showed an increase
      in mass percentage of SiO(2), whereas Opalescence specimens showed a decrease.
      However, there were no significant differences between the groups. CONCLUSION:
      Within the limitations of this study, no significant difference was found between
      bleaching agents. Most changes occurred in the first 2 weeks; the products tested
      were relatively stable in the following test periods. No significant change in
      the surface roughness of feldspathic porcelain was observed. On the other hand,
      the microfilled composite tested showed slight changes in the surface roughness.
      Significant changes were found for the modified glass ionomer cement (P>.005).

PMID- 12806325
TI  - The effect of current bleaching agents on the color of light-polymerized
      composites in vitro.
AB  - STATEMENT OF PROBLEM: Bleaching agents may affect the color of existing composite
      restorations. PURPOSE: The purpose of this study was to compare the effect of 10%
      carbamide peroxide and 10% hydrogen peroxide on the color of light-polymerized
      hybrid, macrofilled, and polyacid-modified composites. MATERIAL AND METHODS: Two
      light-polymerized hybrid composites (3M Valux and Spectrum TPH), 1 macrofilled
      condensable composite (Solitaire), and 2 polyacid-modified composites (Dyract AP
      and Compoglass) were used. The hybrid composites served as controls. The color of
      8 specimens of each material was analyzed by use of a spectrophotometer before
      bleaching. The specimens were then divided randomly into 2 subgroups (n=4). One
      group was immersed in 10% carbamide peroxide solution and the other in 10%
      hydrogen peroxide, for 8 hours each for 14 consecutive days. After bleaching,
      color changes (Delta E) were determined for each material and compared by use of
      the Kruskal-Wallis test, followed by the Mann-Whitney U test (P<.05). RESULTS:
      After bleaching with carbamide peroxide, the color changes (Delta E) for Dyract
      AP (2.18; SD = 1.41), Compoglass (1.14; SD = 0.26) and Solitaire (1.56; SD =
      0.89) were higher than the color changes recorded for 3M Valux (0.63; SD = 3.60),
      and Spectrum TPH (0.66; SD = 1.24). The differences between materials bleached
      with carbamide peroxide were not statistically significant. After bleaching with
      hydrogen peroxide, the color changes for Dyract AP (9.39; SD = 0.53) and
      Compoglass (5.15; SD = 0.52) were higher than the changes recorded for Spectrum
      TPH (4.53; SD = 1.53) and 3M Valux (3.41; SD = 4.40), whereas the color change of
      Solitaire (3.69; SD = 0.57) was significantly higher than that of 3M Valux
      (P=.01). The color changes for all restorative materials tested were clinically
      detectable after the application of 10% hydrogen peroxide. However, clinically
      noticeable discoloration was observed only for Dyract AP treated with 10%
      carbamide peroxide. CONCLUSION: In comparison to 10% carbamide peroxide, 10%
      hydrogen peroxide caused more color changes in the composites tested.

PMID- 12806326
TI  - Effect of etching and airborne particle abrasion on the microstructure of
      different dental ceramics.
AB  - STATEMENT OF PROBLEM: The ceramic composition and microstructure surface of all
      ceramic restorations are important components of an effective bonding substrate.
      Both hydrofluoric acid etching and airborne aluminum oxide particle abrasion
      produce irregular surfaces necessary for micromechanical bonding. Although
      surface treatments of feldspathic and leucite porcelains have been studied
      previously, the high alumina-containing and lithium disilicate ceramics have not
      been fully investigated. PURPOSE: The purpose of this study was to assess the
      surface topography of 6 different ceramics after treatment with either
      hydrofluoric acid etching or airborne aluminum oxide particle abrasion. MATERIAL
      AND METHODS: Five copings each of IPS Empress, IPS Empress 2 (0.8 mm thick),
      Cergogold (0.7 mm thick), In-Ceram Alumina, In-Ceram Zirconia, and Procera (0.8
      mm thick) were fabricated following the manufacturer's instructions. Each coping
      was longitudinally sectioned into 4 equal parts by a diamond disk. The resulting
      sections were then randomly divided into 3 groups depending on subsequent surface
      treatments: Group 1, specimens without additional surface treatments, as received
      from the laboratory (control); Group 2, specimens treated by use of airborne
      particle abrasion with 50-microm aluminum oxide; and Group 3, specimens treated
      with 10% hydrofluoric acid etching (20 seconds for IPS Empress 2; 60 seconds for
      IPS Empress and Cergogold; and 2 minutes for In-Ceram Alumina, In-Ceram Zirconia,
      and Procera). RESULTS: Airborne particle abrasion changed the morphologic surface
      of IPS Empress, IPS Empress 2, and Cergogold ceramics. The surface topography of
      these ceramics exhibited shallow irregularities not evident in the control group.
      For Procera, the 50-microm aluminum oxide airborne particle abrasion produced a
      flattened surface. Airborne particle abrasion of In-Ceram Alumina and In-Ceram
      Zirconia did not change the morphologic characteristics and the same shallows
      pits found in the control group remained. For IPS Empress 2, 10% hydrofluoric
      acid etching produced elongated crystals scattered with shallow irregularities.
      For IPS Empress and Cergogold, the morphologic characteristic was honeycomb-like
      on the ceramic surface. The surface treatment of In-Ceram Alumina, In-Ceram
      Zirconia, and Procera did not change their superficial structure. CONCLUSION:
      Hydrofluoric acid etching and airborne particle abrasion with 50-microm aluminum
      oxide increased the irregularities on the surface of IPS Empress, IPS Empress 2,
      and Cergogold ceramics. Similar treatment of In-Ceram Alumina, In-Ceram Zirconia,
      and Procera did not change their morphologic microstructure.

PMID- 12806327
TI  - Effect of a denture cleanser on weight, surface roughness, and tensile bond
      strength of two resilient denture liners.
AB  - STATEMENT OF PROBLEM: Denture cleansers used in clinical practice can damage
      resilient denture lining materials. PURPOSE: This study evaluated the effects of
      a denture cleanser on weight change, roughness, and tensile bond strength on 2
      denture resilient lining materials. MATERIAL AND METHODS: Forty specimens of
      microwave acrylic resin (Onda-Cryl), 30 mm in diameter and 4 mm thick, were
      prepared to verify weight change and surface roughness. The specimens were
      divided into 4 groups consisting of 10 specimens each, relined with a resilient
      liner (Coe Soft or Dentusoft), and treated (Polident or tap water). To evaluate
      tensile bond strength, 12 specimens were used for each group. All specimens were
      stored in artificial saliva for 15 days, immersed once a day in Polident or tap
      water, and evaluated at 0 hours and after 24 hours and 7 and 15 days. Roughness
      was evaluated by use of a profilometer. Weight changes were recorded in
      milligrams and expressed as the percentage of weight difference between the
      periods of evaluation. Tensile bond strength was determined with a universal
      testing machine. The specimens were placed under tension until failure by a cross
      speed of 5 mm/min with a 500 Kg load cell. The type of failure was determined by
      use of stereoscopic microscopy at original magnification x8. The data were
      submitted to analysis of variance and compared by Tukey's test (alpha=.05).
      RESULTS: Specimens immersed in Polident showed higher and significant (P<.05)
      weight changes (%) than those immersed in water between 24 hours and 7 days (Coe
      Soft-Polident: 0.48 +/- 0.09; Coe Soft-water: 0.28 +/- 0.09; Dentusoft-Polident:
      0.44 +/- 0.16; Dentusoft-water: 0.22 +/- 0.15) and between 7 and 15 days (Coe
      Soft-Polident: 0.08 +/- 0.04; Coe Soft-water: -0.17 +/- 0.05; Dentusoft-Polident:
      0.01 +/- 0.04; Dentusoft-water: - 0.24 +/- 0.03). There was significant
      difference (P<.05) in roughness (in micrometers), between treatments after 7 days
      (Coe Soft-water: 4.07 +/- 0.22; Coe Soft-Polident: 3.36 +/- 0.52; Dentusoft
      water: 3.68 +/- 0.72; Dentusoft-Polident: 3.26 +/- 0.41) and 15 days (Coe Soft
      water: 4.88 +/- 0.29; Coe Soft-Polident:3.53 +/- 0.61; Dentusoft-water: 4.42 +/-
      1.12; Dentusoft-Polident: 3.68 +/- 0.37). Tensile bond strength was highest
      (P<.05) after 15 days (Coe Soft-water: 5.19 +/- 0.93; Coe Soft-Polident: 4.40 +/-
      0.38; Dentusoft-water: 4.42 +/- 1.15; Dentusoft-Polident: 4.84 +/- 1.14). Most
      failures were cohesive (Coe Soft: 76.04% and Dentusoft: 82.29%). CONCLUSION:
      Within the limitations of this in vitro study, specimens immersed in Polident
      demonstrated increased weight changes of resilient liners when compared with tap
      water, but surface roughness and tensile bond strength were unaffected.

PMID- 12806328
TI  - Photoelastic stress analysis of implant-tooth connected prostheses with segmented
      and nonsegmented abutments.
AB  - STATEMENT OF PROBLEM: There is some question about whether implant abutment
      selection affects the transfer of load between connected implants and natural
      teeth. PURPOSE: The purpose of this study was to compare stress transfer patterns
      with either 1 or 2 posterior implants connected to a single anteriorly located
      simulated natural tooth with either 1 or 2 segmented and nonsegmented implant
      abutments under relevant functional loads by use of the photoelastic stress
      analysis technique. MATERIAL AND METHODS: A model of a human left mandible,
      edentulous posterior to the first premolar, with two 3.75-mm x 13-mm screw-type
      implants embedded within the edentulous area, was fabricated from photoelastic
      materials. The implants were in the first and second molar positions. Two fixed
      partial denture prosthetic restorations were fabricated with either segmented
      conical abutments or nonsegmented UCLA abutments. Vertical occlusal loads were
      applied at fixed locations on the restorations. The photoelastic stress fringes
      that developed in the supporting mandible were monitored visually and recorded
      photographically. The stress intensity (number of fringes), stress concentrations
      (closeness of fringes), and their locations were subjectively compared. RESULTS:
      Loading on the restoration over the simulated tooth generated apical stresses of
      similar intensity (fringe order) at the tooth and the first molar implant for
      both abutment types. Low-level stress was transferred to the second molar
      implant. Loading directed on the implant-supported region of the restoration
      demonstrated low transfer of stress to the simulated tooth. Nonvertical stress
      transfer with slightly higher intensity was observed for the nonsegmented
      abutment. CONCLUSION: Within the limitations of this simulation study, stress
      distribution and intensity for the 2 implant conditions was similar for segmented
      and nonsegmented abutment designs. Magnitude of stresses observed for both
      abutment designs was similar for the single implant condition. Vertical loading
      produced more nonaxial stresses away from the force applied for the 1 implant
      condition with the nonsegmented abutment. Direct loading results were similar for
      both abutment designs. Specific recommendations for selection of implant abutment
      and application should be based on clinical criteria.

PMID- 12806329
TI  - The effect of occlusal rest size and shape on yield strength.
AB  - STATEMENT OF PROBLEM: Occlusal rests, essential for conventional removable
      partial dentures, may fracture and cause failure of the prosthesis. It is unknown
      whether alterations in the size or shape of occlusal rests might improve their
      performance. PURPOSE: In this in vitro study, 3-dimensional finite element
      analysis was used to evaluate the effects of occlusal rest size and shape on
      yield strength. MATERIAL AND METHODS: An occlusal rest and a minor connector as
      part of a clasp assembly were modeled for 3-dimensional finite element analysis
      with 3 variations of width (2.0, 3.0, and 4.0 mm), thickness (0.7, 1.0, and 1.5
      mm) and length (2.0, 3.0, and 4.0 mm). A concentrated vertical load of 100 N was
      applied at the most protruded point of the occlusal rest base. Maximal principal
      stress and yield strength were calculated. In addition, the following parameters
      were altered: radius of curvature at the inner connection (r), thickness of the
      minor connector (m), inclination of horizontal axis of occlusal rest (i), and
      thickness at the most protruded point (t). RESULTS: Yield strength increased with
      increased width (183% to 242% from 2.0 to 4.0 mm) and thickness (141% to 230%
      from 0.7 to 1.5 mm). Alterations in length had a lesser effect on yield strength
      (120% to 178% from 4.0 to 2.0 mm). All other parameters except thickness at the
      most protruded point (t) affected yield strength. CONCLUSION: The results of this
      in vitro study suggest basic principles for optimizing the size and shape of
      occlusal rests. In general, increased width and thickness are desirable, whereas
      overrounded or sharp line angles and excessive rest inclination should be
      avoided. These principles may be useful in removable partial denture design.

PMID- 12806330
TI  - Analysis of the condyle/fossa relationship before and after prosthetic
      rehabilitation with maxillary complete denture and mandibular removable partial
      denture.
AB  - STATEMENT OF PROBLEM: The influence of the loss of posterior teeth on the
      condylar position and on temporomandibular disorders (TMDs) remains a
      controversial issue. PURPOSE: This study investigated whether prosthetic
      rehabilitation promoted modification of the condylar position in subjects without
      symptoms of TMDs. MATERIAL AND METHODS: The temporomandibular joints (TMJs) of 12
      women (age 37 to 74), all with existing maxillary complete dentures but no
      removable partial denture (RPD) restoring the Kennedy class I partially
      edentulous mandibular arch and no clinical signs of TMDs according to the
      criteria established by Helkimo, were viewed in maximal intercuspal position with
      corrected lateral tomography before and after prosthetic rehabilitation with a
      new maxillary complete denture and a mandibular RPD. Before prosthetic
      rehabilitation, a mandibular stabilizing base was fabricated to prevent the
      existing maxillary complete denture from dislodging during tomographic
      examination. Two methods were used to evaluate tomograms: (1) linear measurements
      of the subjective narrowest anterior and posterior intra-articular joint spaces
      made from the tomograms by use of a digital caliper and (2) linear measurements
      of the anterior and posterior intra-articular joint spaces on the basis of
      drawings and tracings. Repeated-measures analysis of variance followed by
      orthogonal contrasts were used to evaluate differences between measurements
      carried out on the same subject under the different test conditions of the study
      (before prosthetic rehabilitation, before prosthetic rehabilitation with a
      mandibular stabilizing base in position, and after prosthetic rehabilitation)
      (P<.05). RESULTS: Before prosthetic rehabilitation, a predominance of posterior
      condylar positions was observed. Before prosthetic rehabilitation with a
      mandibular stabilizing base in position, a significant decrease was observed in
      posterior condylar positions (P=.03). This decrease was more marked after
      prosthetic rehabilitation (P=.02). The subjective evaluation and comparison on
      the basis of drawings and tracings used to analyze the tomograms produced similar
      results (P=.70). CONCLUSION: Within the limitations of this study, significant
      changes in the condylar position occurred after prosthetic rehabilitation in
      subjects without symptoms of TMDs.

PMID- 12806331
TI  - A denture tooth position index fabricated with light-polymerized acrylic resin.
AB  - A denture tooth position index transfers the position of the denture teeth to the
      master cast during metal framework and bar-substructure fabrication stage. This
      article describes the use of light-polymerizing acrylic resin to fabricate a
      tooth position index.

PMID- 12806332
TI  - A shade selection technique.
AB  - The purpose of this article is to present a variation on the standard technique
      of shade selection by use of the Vitapan 3-D master "tooth" guide and the Vitapan
      3-D master "dentin" guide together. The dentin guide is used first to select the
      shade determinants, and the tooth guide is used to verify them.

PMID- 12806333
TI  - Removing crowns with minimal damage.

PMID- 12806334
TI  - Protecting the privacy of your patients.

PMID- 12806335
TI  - The myth of Janus: Orthodontic progress faces orthodontic history.

PMID- 12806336
TI  - Outcome of orthodontic space closure with a missing maxillary central incisor.
AB  - Orthodontic space closure is one of the treatment alternatives when a maxillary
      central incisor is missing. Because no systematic analysis of such treatment
      results is available, a sample of 20 consecutively treated patients was examined
      in a follow-up study. All patients had received orthodontic treatment with the
      objective of closing the space for the missing central incisor. Biologic features
      and the clinical appearance of the recontoured lateral incisor (test tooth)
      replacing the missing tooth were compared with the neighboring intact central
      incisor, which served as control tooth. The patients' opinions regarding the
      treatment and the result were recorded in a questionnaire. The position of the
      examined teeth and the appearance of the surrounding soft tissues were similar in
      the test and control teeth. However, in some patients (25%), certain aspects of
      the recontoured incisor crown (such as the width at the gingival margin)
      mismatched the appearance of the controls. A somewhat increased mobility and
      probing pocket depth on the mesial aspect was recorded for some test teeth. No
      obvious detrimental effects were observed on the radiographs. Most patients
      expressed satisfaction with the treatment result. It is concluded that
      orthodontic mesialization of the lateral incisor to replace a missing central
      incisor is a valid treatment modality, if the indications for such treatment are
      present and careful attention to detail in orthodontic and restorative treatment
      is exercised.

PMID- 12806337
TI  - Condyle-fossa modifications and muscle interactions during herbst treatment, part
      1. New technological methods.
AB  - Changes in the condyle, the glenoid fossa, and the muscles of mastication were
      investigated in subjects undergoing continuous orthopedic advancement of the
      mandible with a Herbst-block appliance. The total sample consisted of 56 subjects
      and included 15 nonhuman primates (in the middle mixed, early permanent, and
      permanent dentitions), 17 human Herbst patients in the early permanent dentition,
      and 24 human controls from the Burlington Growth Center. The 8 nonhuman primates
      in the middle mixed dentition were the focus of this study. Mandibular
      advancement was obtained progressively in 5 animals by adding stops to the
      telescopic arms of fixed functional Herbst appliances with occlusal coverage;
      activations of 5.0 mm, 7.0 mm, and 8.0 mm were achieved. Two primates served as
      controls, and the third was a sham control. Two experimental animals and the 2
      controls also wore surgically implanted electromyographic electrodes in the
      superior and inferior heads of the lateral pterygoid muscles and in the
      superficial masseter and anterior digastric muscles. Changes in condylar growth
      direction and amount were assessed with the Bjork method from measurements made
      on serial cephalometric tracings superimposed on metallic implants. Undecalcified
      sections, treated with intravenous tetracycline vital staining, were viewed with
      fluorescence microscopy to examine histologic changes in the condyle and the
      glenoid fossa. New bone formation in the fossa associated with continuous
      mandibular protrusion was quantified by using computerized histomorphometric
      analysis of decalcified histological sections and polarized light. The unique
      combination of permanently implanted electromyographic electrodes, tetracycline
      vital staining, and histomorphometry represents a significant technological
      advancement in methods and materials. Together, they demonstrated different
      muscle-bone interaction results for functional appliances than those reported in
      previous studies. In Part 1 of this study, we describe and discuss the techniques
      used in this research and give a brief overview of the findings; in Part 2 (to be
      published next month), we offer a more in-depth discussion of the results and the
      implications of our findings.

PMID- 12806338
TI  - Tooth size-arch length relationships in the deciduous dentition: a comparison
      between contemporary and historical samples.
AB  - In a recent study, it was reported that maxillary and mandibular arch lengths
      were significantly shorter in a sample of contemporary children in the deciduous
      dentition compared with a historical sample from about 50 years earlier. The
      purpose of this study was to describe secular changes that might have occurred in
      tooth sizes and tooth size-arch length relationships in the same cohorts of
      contemporary and historical North American white children in the deciduous
      dentition. The 2 samples were similar in terms of geographic location, racial and
      ethnic backgrounds, and socioeconomic status. Both samples were restricted to
      white children with a normal overjet (<4 mm) and a normal anteroposterior molar
      relationship, no anterior open bite, and no crossbite. In addition, subjects were
      excluded if any permanent teeth were erupted. Measurements of mesiodistal tooth
      sizes and arch lengths of maxillary and mandibular arches were made, and tooth
      size-arch length discrepancies (TSALD) were determined. The results indicated
      that tooth sizes were generally similar in the 2 cohorts but slightly larger in
      contemporary children. Crowding, as measured by TSALD, was found to be common in
      the mandibular arch for contemporary children in the deciduous dentition of both
      boys and girls. Moreover, crowding was much more common and severe in
      contemporary children compared with children in the historical cohort. Further
      research is needed to determine whether the increase in mandibular crowding in
      the deciduous dentition will continue to be observed in the mixed and permanent
      dentitions and to further establish these possible secular trends.

PMID- 12806339
TI  - Prevalence of otologic complaints in patients with temporomandibular disorder.
AB  - The prevalence and rank of order of 4 otologic complaints in 200
      temporomandibular disorder (TMD) patients, as well as the relationship between
      the complaints and TMD subgroups, were investigated and compared with an
      asymptomatic control group. No subjective otologic complaints were reported by 45
      (22.5%) TMD patients; the remaining 155 (77.5%) patients had at least 1 otologic
      complaint. Otalgia, tinnitus, vertigo, and hearing loss were reported by 63.6%,
      59.1%, 50%, and 36.4%, respectively, of the subjects with myofascial pain and
      dysfunction; by 46.1%, 44.2%, 32.5%, and 22% of the patients with internal
      derangement; and by 62.5%, 45.8%, 41.6%, and 20.8% of the patients with both
      myofascial pain and dysfunction and internal derangement. However, the incidence
      of otalgia (8%), tinnitus (26%), vertigo (14%), and hearing loss (14%) was found
      to be lower for the control group. Statistically, the control group had fewer
      otologic complaints. Patients in the TMD groups had high incidences of otologic
      complaints compared with the control subjects without TMD signs or symptoms.
      Aural symptoms in patients with internal derangement or myofascial pain and
      dysfunction, or their combination, were nonspecific.

PMID- 12806340
TI  - Bond failure and decalcification: A comparison of a cyanoacrylate and a composite
      resin bonding system in vivo.
AB  - This prospective, in vivo study compared bond failure and enamel decalcification
      with a cyanoacrylate bracket bonding system (SmartBond, Gestenco International,
      Gothenburg, Sweden) and a traditional light-cured composite system (Light Bond,
      Reliance Orthodontic Products, Itasca, Ill). A total of 327 teeth were evaluated
      after a period of 12 to 14 months; 163 experimental teeth were bonded with the
      cyanoacrylate bonding system, and 164 control teeth were bonded with the light
      cured composite resin. All teeth were evaluated for breakage (bond failure). The
      average percentage of bracket failures with cyanoacrylate was 55.6% compared with
      11.3% with composite resin (P <.001). All maxillary anterior teeth (94) were
      evaluated for enamel decalcification on a graded scale. Occurrence of enamel
      decalcification between the 2 bonding systems after 1 year of orthodontic
      treatment was similar. The cyanoacrylate bonding material had more than 4 times
      as many bond failures and a similar amount of decalcification as the traditional
      composite material. Cyanoacrylate as a routine orthodontic bonding agent is not a
      suitable bonding material for clinical practice at this time. It is important to
      test new bonding systems in vivo in several studies before using them in routine
      clinical practice.

PMID- 12806341
TI  - Can previously bleached teeth be bonded safely?
AB  - The purpose of our study was to determine the effect of a 35% hydrogen peroxide
      bleaching agent on the shear bond strength of metallic orthodontic brackets.
      Sixty premolars were randomly divided into 3 groups of 20 each. Teeth in group A
      were etched with 37% phosphoric acid before bonding metallic premolar brackets.
      Teeth in the other 2 groups were bleached with a 35% hydrogen peroxide in-office
      bleaching agent according to the manufacturer's recommendations. Twenty bleached
      teeth (group B) were bonded immediately, and the other 20 (group C) were stored
      in artificial saliva for 30 days before bonding. Shear bond strength of these
      brackets was measured on a universal testing machine and recorded in MPa.
      Adhesive remnant index (ARI) scores were determined after the brackets failed.
      Data were analyzed with analysis of variance (ANOVA) and chi-square tests. The
      shear bond strength values of groups A, B, and C were 12.9 +/- 3.4, 12.0 +/- 4.6,
      and 14.8 +/- 4.0 MPa, respectively. Results of ANOVA showed no statistically
      significant differences in shear bond strengths between groups (P >.05). ARI
      scores were significantly different in all groups. The unbleached group's
      failures were primarily at the bracket/adhesive interface, whereas the bleached
      groups either showed cohesive failures within the adhesive or failed at the
      adhesive/enamel interface. The results of this study suggest that office
      bleaching with hydrogen peroxide does not adversely affect the bond strengths of
      brackets bonded immediately after bleaching or 30 days after bleaching, even
      though bleaching can result in differences in the failure site.

PMID- 12806342
TI  - Effect of water and saliva contamination on shear bond strength of brackets
      bonded with conventional, hydrophilic, and self-etching primers.
AB  - This study assessed the effect of water and saliva contamination on the shear
      bond strength and bond failure site of 3 different orthodontic primers (Transbond
      XT, Transbond Moisture Insensitive Primer, and Transbond Plus Self Etching
      Primer; 3M Unitek, Monrovia, Calif) used with a light-cured composite resin
      (Transbond XT). Bovine permanent mandibular incisors (315) were randomly divided
      into 21 groups (15 in each group). Each primer-adhesive combination was tested
      under 7 different enamel surface conditions: (1) dry, (2) water application
      before priming, (3) water application after priming, (4) water application before
      and after priming, (5) saliva application before priming, (6) saliva application
      after priming, and (7) saliva application before and after priming. Stainless
      steel brackets were bonded in each test group with composite resin. After
      bonding, all samples were stored in distilled water at room temperature for 24
      hours and then tested for shear bond strength. Noncontaminated enamel surfaces
      had the highest bond strengths for conventional, hydrophilic, and self-etching
      primers, which produced the same strength values. In most contaminated
      conditions, the self-etching primer had higher strength values than either the
      hydrophilic or conventional primers. The self-etching primer was the least
      influenced by water and saliva contamination, except when moistening occurred
      after the recommended 3-second air burst. No significant differences in debond
      locations were found among the groups bonded with the self-etching primer under
      the various enamel conditions.

PMID- 12806343
TI  - Effects of fast halogen and plasma arc curing lights on the surface hardness of
      orthodontic adhesives for lingual retainers.
AB  - The aims of this study were to (1) identify the optimum cure times of 2 different
      lingual retainer adhesives with a conventional halogen, a fast halogen, and a
      plasma arc light by measuring Vickers surface hardness, and (2) determine whether
      different lights produce similar surface hardness values for the same adhesive
      resin material. The investigated plasma arc curing unit was the PowerPac
      (American Dental Technologies, Corpus Christi, Tex), and the fast halogen unit
      was the Optilux 501 (Kerr, Orange, Calif). A conventional curing unit, the
      Ortholux XT (3M Dental Products, St. Paul, Minn) was used as the control. Two
      orthodontic lingual retainer adhesives were used: Transbond Lingual Retainer (3M
      Unitek, Monrovia, Calif) and Light Cure Retainer (Reliance Orthodontic Products,
      Itasca, Ill). Concise (3M Dental Products) and diluted Concise were used as
      controls. Transbond Lingual Retainer was polymerized by the PowerPac light in 6
      seconds, by the Optilux in 10 seconds, and by the conventional halogen light in
      20 seconds. The minimum curing times for Light Cure Retainer adhesive were 15
      seconds for PowerPac, 10 seconds for Optilux, and 40 seconds for conventional
      halogen. Surface hardness values for each resin did not differ significantly with
      different curing units. However, different adhesives demonstrated significantly
      different surface hardness values. Final Vickers surface hardness values
      (averaged across curing units) of Transbond Lingual Retainer, Concise, diluted
      Concise, and Light Cure Retainer were 62.8, 52.4, 46.0, and 40.4, respectively.
      Plasma arc or fast halogen units polymerize resin composite adhesive in much
      shorter times than do conventional curing units, without a significant loss in
      surface hardness. Therefore, these units are suggested for clinical use to save
      chairside time.

PMID- 12806344
TI  - Evaluation of a new 2-paste glass ionomer cement.
AB  - A new 2-paste resin-reinforced glass ionomer cement, Fuji Ortho Band Paste Pak
      (GC Corporation, Tokyo, Japan), for the placement of orthodontic bands, has been
      developed for easier handling. The aim of this study was to compare the fluoride
      release and uptake characteristics of this cement with that of 3 others commonly
      used to cement orthodontic bands: a conventional resin-reinforced glass ionomer
      cement, a polyacid-modified composite resin, and a conventional glass ionomer
      cement. Fluoride release was measured during a 28-day period. After the
      measurement on day 28, experimental samples were exposed to 1000 ppm sodium
      fluoride solution for 5 minutes, and fluoride release was then measured for 7
      days. Initially, the new 2-paste resin-reinforced glass ionomer cement released
      the greatest amount of fluoride; the polyacid-modified composite resin released
      the least initially, and it continued to show the lowest values throughout the
      study. The fluoride uptake and release values of the new 2-paste resin-reinforced
      glass ionomer cement were statistically significantly higher than those of the
      conventional resin-reinforced glass ionomer cement or the conventional glass
      ionomer cement. The new 2-paste resin-reinforced glass ionomer cement might be a
      good alternative to conventional products for cementing orthodontic bands.

PMID- 12806345
TI  - Surface changes induced by fluoride prophylactic agents on titanium-based
      orthodontic wires.
AB  - This study investigated the effect of fluoride prophylactic agents on the
      surfaces of titanium-based orthodontic wires. Four types of titanium-based
      orthodontic wires (2 nickel-titanium alloy wires [nickel-titanium and copper
      nickel-titanium] and 2 beta-titanium alloy wires [titanium-molybdenum and
      titanium-niobium], all from Ormco, Glendora, Calif) with similar sizes were
      prepared and immersed in 5 fluoride prophylactic agents (2 acidulated phosphate
      fluoride agents [Nupro APF (Dentsply International, York, Pa) and Florentine III
      (Confi-Dental, Louisville, Colo)], 1 neutral agent [Neupro Neutral (Dentsply
      International)] and 2 stannous fluoride agents [Florentine II (Confi-Dental) and
      Perio-Med (Omni International, Warrenton, Va)]) for 5 minutes, 1 hour, and 24
      hours. After immersion, average surface roughness and color changes were
      evaluated. The surface changes were observed with a scanning electron microscope.
      The average surface roughness data were statistically analyzed by analysis of
      variance and Tukey post hoc test at a significance level of alpha = 0.05. There
      were no significant differences in average surface roughness value among fluoride
      solutions or orthodontic wires, except for the titanium-molybdenum wire, which
      showed significantly (P <.05) higher average surface roughness values after
      immersion in Nupro APF for 24 hours. The results suggested that a few
      applications of acidulated phosphate fluoride agents might change the surface
      color of the beta-titanium alloy wires, particularly the titanium-molybdenum
      wire, which contains a large amount (about 80%) of titanium.

PMID- 12806346
TI  - A nonlinear finite element analysis of the periodontal ligament under orthodontic
      tooth loading.
AB  - The stressed state of the periodontal ligament (PDL) is understood to play a
      critical role in the tooth movement initiated by orthodontic treatment. Finite
      element simulations have been used to describe PDL stresses for orthodontic
      loading; however, these models have predominantly assumed linear mechanical
      properties for the PDL. The present study sought to determine the importance of
      using nonlinear mechanical properties and nonuniform geometric data in computer
      predictions of periodontal ligament stresses and tooth movements. A 2-dimensional
      plane-strain finite element model of a mandibular premolar was constructed based
      on anatomic data of transverse sections of tooth, PDL, and bone from a 24-year
      old cadaveric man. A second model was constructed of the same tooth but with a
      PDL of uniform thickness. Each of these was prescribed linear or nonlinear
      elastic mechanical properties, as obtained in our own experiments. Predictions of
      the maximum and minimum principal stresses and von Mises stresses in the PDL were
      determined for extrusive and tipping forces. The results indicated that
      biofidelic finite element models predicted substantially different stresses in
      the PDL for extrusive loading than did the uniform thickness model, suggesting
      that incorporation of the hourglass shape of the PDL is warranted. In addition,
      incorporation of nonlinear mechanical properties for the PDL resulted in dramatic
      increases in the stresses at the apex and cervical margin as compared with the
      linear models.

PMID- 12806347
TI  - Orthodontic movement of teeth with intraosseous defects: Histologic and
      histometric study in dogs.
AB  - The purpose of this study was to evaluate histologically, in dogs, the
      periodontal healing of 1-walled intraosseous defects in teeth that were subjected
      to orthodontic movement toward the defects. The defects were surgically created
      bilaterally at the mesial aspects of the maxillary second premolars and distal
      aspects of the mandibular second premolars of 4 mongrel dogs. One week after
      creating the defects, an orthodontic appliance was installed, and the teeth were
      randomly assigned to 1 of 2 treatment groups: those in the test group received a
      titanium-molybdenum alloy rectangular wire spring that performed a controlled
      tipping root movement, and those in the control group received a passive
      stainless steel wire. Active orthodontic movement of the test teeth lasted 2
      months and was followed by a stabilization period of another 2 months, after
      which the animals were killed. Throughout the study, routine daily plaque control
      was performed on the dogs with a topical application of a 2% chlorhexidine gel.
      The results showed no difference between the groups, with some regularization of
      the defects and periodontal regeneration limited to the apical portion of the
      defects. Histometric analysis showed a significant difference in bone height; on
      average, it was 0.53 mm smaller in the test group. It was concluded that
      orthodontic movement does not interfere with the healing of 1-walled intraosseous
      defects, with the exception of the linear extent of new bone apposition.

PMID- 12806350
TI  - Congenitally missing mandibular second premolar: treatment outcome with
      orthodontic space closure.
AB  - Orthodontic treatment for patients with congenitally missing mandibular second
      premolars can be challenging. Treatment options include keeping the deciduous
      second molar, extracting the molars and allowing the space to close
      spontaneously, autotransplantation, prosthetic replacement, and orthodontic space
      closure. Space closure with orthodontic appliances is demonstrated in this case
      report.

PMID- 12806351
TI  - Dental distraction for an adult patient.

PMID- 12806352
TI  - Intrusion of posterior teeth using mini-screw implants.
AB  - It is often difficult to perform prosthodontic treatment for missing molars
      because the antagonist has become extruded. However, some problems can be
      overcome with successful molar intrusion with mini-screws if the direction and
      the amount of force are carefully controlled.

PMID- 12806353
TI  - Job satisfaction among Canadian orthodontists.
AB  - Job satisfaction has been well researched for many professions, including general
      dentistry. The job satisfaction of orthodontists has not been adequately studied.
      The aims of this study were to describe job satisfaction among orthodontists and
      to determine characteristics associated with job satisfaction in the profession.
      A self-administered, anonymous survey was mailed to Canadian orthodontists. It
      included a modified version of the Dentist Satisfaction Survey, an overall
      occupational stress score, and items addressing various characteristics of the
      respondents. Of 654 mailed surveys, 335 were returned, for a response rate of
      51.2%. Most orthodontists (79.3%) were classified as satisfied according to the
      overall job satisfaction scale of the Dentist Satisfaction Survey; however, some
      (2.5%) were classified as dissatisfied. The facets of orthodontics with the
      highest degree of satisfaction were patient relations (93%), delivery of care
      (86%), respect (84%), professional relations (80%), and staff (76%). The most
      dissatisfaction was associated with personal time (26%) and practice management
      (15%). Stepwise multiple regression analysis resulted in a model including
      overall occupational stress, membership in the Canadian Association of
      Orthodontists, total number of staff, and age to account for 27.1% of the
      variation in the overall job satisfaction scale. Based on accountable sources of
      variance, the overall job satisfaction scale seems to be more affected by other
      variables than the characteristics evaluated by this survey.

PMID- 12806354
TI  - The office technology backbone.

PMID- 12806355
TI  - Litigation, legislation, and ethics. Benedict Arnold as an expert witness.

PMID- 12806356
TI  - Inadequacy of manual cleaning for reprocessing single-use, triple-lumen
      sphinctertomes: simulated-use testing comparing manual with automated cleaning
      methods.
AB  - BACKGROUND AND AIMS: Despite widespread reuse of single-use sphinctertomes,
      publications regarding the adequacy of reprocessing are conflicting and the
      cautery wire channel is seldom evaluated. Our objective was to use thickened
      artificial test soil containing microorganisms to perform simulated-use tests
      combined with in-situ and destructive testing to evaluate cleaning efficacy and
      ethylene oxide sterilization of single-use triple lumen sphinctertomes. METHODS:
      New triple-lumen sphinctertomes were soiled with thickened artificial test soil
      containing 6 log(10) per milliliter of Enterococcus faecalis and Bacillus
      stearothermophilus by inoculation through the distal end and dried for 1 hour, 24
      hours, or 7 days before cleaning. The efficacy of manual cleaning was compared
      with that of automated cleaning with the Medisafe SI-Auto narrow-lumen cleaner.
      After cleaning, Bradford's reagent was injected into the channels as a direct
      method of detecting residual protein. Destructive testing was done to determine
      the levels of residual protein, carbohydrate, hemoglobin, endotoxin, and viable
      bacteria in the cleaned device. Destructive sterility testing of the devices also
      was performed after ethylene oxide sterilization. RESULTS: Both in-situ and
      destructive testing demonstrated that manual cleaning and automated washers
      connected via the luer ports did not remove soil or organisms from the cautery
      wire channel. Only retro-flushing in the SI-Auto provided adequate cleaning of
      all 3 channels. If reprocessing was delayed for more than 24 hours, retro-flush
      cleaning was no longer effective. Ethylene oxide sterilization failure was
      detected only for devices held for 7 days before cleaning and sterilization. In
      use testing showed that patient secretions gained access to the cautery wire
      channel. CONCLUSIONS: Only retro-flushing done within 24 hours of use provided
      adequate cleaning for multi-lumen, single-use sphinctertomes. Our data validate
      the efficacy of reprocessing sphinctertomes once with SI-Auto retro-flush
      cleaning followed by 2 hours of ethylene oxide sterilization.

PMID- 12806357
TI  - Persistent silver disinfectant for the environmental control of pathogenic
      bacteria.
AB  - BACKGROUND: Contaminated surfaces can act as a reservoir for pathogenic
      microorganisms and potentially exacerbate the risk of infection. Surface
      disinfection and decontamination provide temporary amelioration against bacterial
      colonization. Disinfected surfaces eventually become contaminated, thus,
      mitigating the benefit of the initial disinfection. It is hypothesized that to
      improve on the current state of the art, a disinfectant should not only
      immediately disinfect a surface but also provide persistent antimicrobial action
      after the product has been applied. We describe here a silver-based disinfectant
      technology designed to provide long-lasting sanitization and disinfection to
      treated surfaces as evaluated on hard surfaces after repeated environmental
      insults. METHODS: A comparative evaluation of 6 disinfectant formulations for
      residual antimicrobial activity after water rinsing was performed. Log reduction
      of bacterial populations on disinfectant-treated substrates were measured after
      30 minutes to 8 hours of exposure and compared with an untreated control. In a
      similar study, the residual antimicrobial activity of a silver disinfectant was
      evaluated against antibiotic- and biocide-resistant bacteria also after water
      rinsing. Further, residual antimicrobial activity of the silver disinfectant was
      measured after 5 cycles of rinsing, abrasion, and contamination against
      representative household and nosocomial pathogens (Escherichia coli,
      Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes,
      Enterococcus faecium, or Salmonella choleraesuis) after 10-minute exposure times.
      RESULTS: In the comparative assay, only the silver disinfectant and a persistent
      quaternary ammonium compound disinfectant demonstrated significant residual
      activity (> or =3.0 log(10) reduction to control) against S aureus whereas only
      the silver disinfectant demonstrated activity against Pseudomonas. No residual
      activity (< or = 0.5 log reduction to untreated control) was observed for the
      other disinfectant products. The silver-based disinfectant also showed
      significant and equivalent efficacy against antibiotic- and silver-resistant
      bacteria. In addition, the silver disinfectant was able to achieve significant
      residual activity in 10 minutes against all organisms tested after 1, 3, and 5
      cycles of water rinse, abrasion, and microbial contamination. CONCLUSIONS: The
      findings show the ability of a new silver-based disinfectant to reduce bacterial
      populations that contact treated surfaces within minutes, highlight the potential
      to interrupt cross-contamination from environmental surfaces, and reduce the risk
      of infection within the home and health care settings.

PMID- 12806358
TI  - Investigation of infection control practices and knowledge of hepatitis C among
      body-piercing practitioners.
AB  - BACKGROUND: Body piercing has become increasingly popular, leading to concerns
      about the associated risk of hepatitis C virus (HCV) transmission during
      piercing. Many body-piercing practitioners (BPPs) have recently entered the
      industry but little is known about their training and understanding of HCV
      transmission. This study measured BPP knowledge about HCV and infection control
      procedures. It also tested for HCV contamination within body-piercing
      establishments. METHODS: BPPs completed a questionnaire about the number and type
      of piercings performed, their methods for disposing of and reprocessing piercing
      equipment, and their training and knowledge of HCV. Environmental swabs were
      collected and tested for HCV RNA. RESULTS: BPPs at 35 establishments were
      recruited. A total of 31 BPPs had training as a BPP, ranging from 1 hour to 6
      years (median: 15 days). Reprocessing of equipment was variable; 8 establishments
      inadequately reprocessed piercing guns and 4 inadequately reprocessed forceps or
      guiding equipment. All BPPs were aware of HCV but many did not know how the virus
      was transmitted. A total of 19 BPPs performed extra cleaning after piercing a
      customer known to be HCV positive. No environmental swabs tested were positive
      for HCV RNA. CONCLUSIONS: This study showed that many BPPs had inadequate
      training, and lacked knowledge and understanding of HCV transmission, infection
      control, and universal precautions. To reduce the risk of HCV transmission, BPPs
      should be required to undergo formal training in infection control before being
      registered as BPPs.

PMID- 12806359
TI  - Role of fecal incontinence in contamination of the environment with vancomycin
      resistant enterococci.
AB  - BACKGROUND: We tested the hypothesis that patients with vancomycin-resistant
      Enterococcus (VRE) stool colonization who are continent of feces contaminate the
      environment less frequently than patients who are colonized and incontinent.
      METHODS: We prospectively examined the frequency of environmental VRE
      contamination in the rooms of 15 patients who were continent and 15 who were
      incontinent and VRE-colonized. Broth-enrichment cultures of bed rails, bedside
      table, and call buttons were performed at baseline, and 2 and 5 days after
      environmental disinfection. The numbers of VRE colonies isolated after directly
      plating environmental swabs onto agar were compared for the continent and
      incontinent groups. RESULTS: The percentages of patients with 1 or more positive
      environmental cultures for VRE were not significantly different for the groups of
      patients who were continent and incontinent at baseline (60% vs 73%, P =.45) or 2
      days after disinfection (60% vs 80%, P =.24). The numbers of VRE colonies
      isolated by direct plating were not significantly different for the continent and
      incontinent groups (P =.42). CONCLUSIONS: Environmental contamination occurs
      frequently in the rooms of patients who are continent, and those who are
      incontinent and VRE-colonized. Our findings suggest that similar infection
      control measures should be implemented for patients who are continent and
      incontinent.

PMID- 12806360
TI  - Needlestick injuries among medical students.
AB  - BACKGROUND: Concern about occupational exposure to bloodborne pathogens exists,
      and medical students, who lack in experience in patient care and surgical
      technique, may be at an increased exposure risk. METHODS: This prospective cohort
      study evaluated needlestick injuries and practices regarding the use of
      protective strategies against bloodborne pathogens in medical students. A
      questionnaire was developed and sent to 224 medical students. RESULTS: Of 224
      students, 146 students (64%) returned questionnaires. Forty-three students (30%)
      reported needlestick injuries that most commonly occurred in the operating room;
      86% of students reported always using double gloves in the operating room; 90%
      reported always wearing eye protection, and all but one student had been
      vaccinated against hepatitis B. A concern about contracting a bloodborne pathogen
      through work was noted in 125 students, although they usually reported that this
      concern only slightly influenced their decision regarding a career subspecialty.
      CONCLUSION: Medical students have a high risk for needlestick injuries, and
      attention should be directed to protection strategies against bloodborne
      pathogens.

PMID- 12806361
TI  - Attitudes of a group of Mexico City residents toward HIV/AIDS in the dental
      office.
AB  - OBJECTIVE: To ascertain the intention of the public to undergo dental treatment
      at dental clinics where other patients or a dentist are infected with HIV/AIDS.
      STUDY DESIGN: A cross-sectional design was used to interview a stratified sample
      of persons 18 years and older in Mexico City with use of a standardized
      questionnaire. Questions included the type of dental service used, the perception
      of risk for HIV/AIDS contagion in the dental environment, and the reported
      intention to continue treatment in a dental office where patients or a dentist
      were affected by HIV/AIDS. RESULTS: Of the 490 participants, 74.9% were concerned
      about HIV/AIDS transmission in the dental office. Only 21.2% intended to continue
      treatment at a dental office where HIV/AIDS patients were treated, and only 20.0%
      intended to continue treatment when the dentist was HIV-positive. The degree of
      concern about HIV/AIDS contagion and the modality of dental service used were
      associated with the stated intention to continue dental treatment. CONCLUSIONS:
      There is a need to have good infection control standards in dental practice; to
      increase public trust in such standards by making them more apparent; and/or to
      establish educational programs to improve public knowledge and attitudes toward
      HIV/AIDS risks in dental practice.

PMID- 12806362
TI  - Comparison of US and non-US central venous catheter infection rates: evaluation
      of processes and indicators in infection control study.
AB  - OBJECTIVE: We sought to identify the presence or absence of international
      variation in central venous catheter-associated bloodstream infection (BSI) rates
      and to examine associated infection control practices that might underlie the
      differences. DESIGN: The Evaluation of Processes and Indicators in Infection
      Control (EPIC) study was conducted as a prospective surveillance study. SETTINGS:
      The study took place in intensive care units (ICUs) from 14 countries, which were
      from the Asian Pacific (3), Europe (7), Middle East (2), and South America (2),
      in addition to 41 US hospitals. METHODS: We compared the National Nosocomial
      Infections Surveillance catheter-associated BSI rate between the non-US and US
      units. We also compared the following organization factors between the 2 groups:
      hospital factors (ownership, average daily census of patients); ICU type (medical
      vs surgical); number of beds; and infection control-related factors (number of
      staff, number of hours spent on study ICU surveillance, years of experience,
      number of inservice sessions on line infection, number of blood cultures
      drawn/1000 patients). RESULTS: We found no significant difference in catheter
      associated BSI rates between non-US and US hospitals (5.02 +/- 0.75 vs 3.82 +/-
      0.42/1000 days, respectively; P =.27). Non-US hospitals were more likely to be
      government-owned (10/14 vs 7/41;P <.001) and to have larger daily patient census
      (795 +/- 84 vs 276 +/- 47 patients; P <.001). There was no difference in ICU type
      or number of beds. Infection control committees were present in all US and non-US
      hospitals. No significant differences were found in the number of staff involved
      in surveillance in the study ICU, years of experience, hours spent on
      surveillance, or the provision of inservices on line care. The use of barriers
      during line insertion also did not differ. CONCLUSIONS: Catheter-associated BSIs
      in patients in the ICU were not significantly different between non-US and US
      hospitals. All hospitals had infection control committees, and there were no
      significant differences in time spent and numbers of persons involved in ICU
      surveillance activities. These findings suggest that many aspects of the
      standards of care do not differ between the 2 groups.

PMID- 12806363
TI  - Disinfection and the prevention of infectious disease.
AB  - This article reviews published literature to determine the role environmental
      disinfection plays in the prevention of infectious disease. Health benefits from
      disinfection have been established through studies of applications such as
      critical instrument sterilization, water treatment, and food production.
      Guidelines by the Centers for Disease Control and Prevention, the Food and Drug
      Administration, the Environmental Protection Agency, and the International
      Scientific Forum on Home Hygiene acknowledge the incidence of disease due to
      insufficient disinfection and that one of the means for prevention of disease is
      through proper disinfection. Studies conducted in day care centers, long-term
      care facilities, and laboratories show that disinfectants containing a variety of
      active ingredients demonstrated efficacy against a broad spectrum of pathogens
      and interrupted microbial transmission and that the use of disinfectants results
      in public health benefits.

PMID- 12806364
TI  - Contaminated iodophor in the operating room.

PMID- 12806365
TI  - Use of containment pans and lids for autoclaving caustic solutions.
AB  - As a means of decontaminating instruments possibly exposed to Creutzfeldt-Jakob
      disease, the World Health Organization has recommended immersion and autoclaving
      in sodium hydroxide. However, this recommendation has raised concerns of possible
      damage to autoclaves, and hazards to operators as a result of the caustic vapors.
      A series of experiments has been conducted that demonstrate that there are
      containment pan-and-lid combinations in which instruments can be autoclaved in
      sodium hydroxide without risk to the autoclave or the operator.

PMID- 12806368
TI  - Treatment modalities of bladder/prostate rhabdomyosarcoma: a review.
AB  - Treatment outcomes of bladder/prostate rhabdomyosarcoma (RMS) in multi- and
      single-institutional trials are reviewed. Remarkable strides have occurred in the
      treatment of this disease. Decreasing duration of chemotherapy, less cumulative
      doses of radiation therapy, and improving survival have been documented. A focus
      on bladder preservation has not adversely affected survival in most studies. Even
      if organ preservation is not possible, improvements in urinary diversion surgical
      technique still offer improved quality of life. The IRS III was a pivotal study
      in improving survival and quality of life. We recommend protocol enrollment
      whenever available. We also emphasize the use of magnetic resonance imaging and
      second look surgery.

PMID- 12806370
TI  - Gene delivery into prostate cancer cells by holmium laser application.
AB  - New approaches to treat prostate cancer (PCA) are utilizing gene therapy and aim
      to correct the disease at the genetic level. Getting a gene efficiently into the
      target cell is the subject of much interest. We used a holmium laser for
      transfecting rat PCA cells with the reporter gene pEGFP. By FACS analysis and
      fluorescence microscopy, we could demonstrate that cellular delivery of plasmid
      DNA was possible with high efficiencies up to 41.3%. Therefore, transfection of
      PCA cells by holmium laser might offer a promising new gene transfer strategy to
      PCA with minimal invasiveness.

PMID- 12806369
TI  - Transurethral electrovaporization of the prostate (TUVP) is effective, safe and
      durable.
AB  - Transurethral electrovaporization of the prostate (TUVP) is one of the
      alternative, minimally invasive procedures to treat BPH with promising initial
      results. We reviewed the available English literature to evaluate the long-term
      safety, efficacy and durability of TUVP using various vaporizing electrodes. We
      performed a MEDLINE keyword search and assessed all prospective randomized
      studies, which compared TUVP to standard transurethral resection of the prostate
      (TURP) that reached 1 y follow-up. Data were analysed for improvement of IPSS and
      Q(max), operation time, hospital stay, perioperative bleeding, postoperative
      irritative symptoms, long-term side effects and reoperation rate. We reviewed a
      total of 244 TUVP compared to 259 TURP patients in six prospective randomized
      studies that reached 1 y follow-up. Less perioperative bleeding, shorter
      catheterization time (mean of TUVP: 30 h vs TURP: 61 h) and shorter hospital stay
      (mean of 1.4 days vs TURP: 3.4 days) were reported in the TUVP patients. The
      improvement in IPSS (71%) and mean Q(max) (20 ml/s) was similar in both groups.
      The reoperation rate was 2% per year in both vaporization and resection patients.
      In conclusion, analysis of the prospective randomized trials that reached 1 year
      follow-up revealed that TUVP is as effective as standard TURP in the treatment of
      BPH. Long-term side effects and reoperation rates are comparable and the initial
      improvement was maintained over 1 year for the majority of patients.

PMID- 12806371
TI  - Elements regulating angiogenesis and correlative microvessel density in benign
      hyperplastic and malignant prostate tissue.
AB  - PURPOSE: To quantify the ex vivo production of proangiogenic proteins (vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator
      (tPA)) and angiogenesis inhibitors (plasminogen activator inhibitor type-1 (PAI
      1) and angiostatin) from epithelial and stromal components of primary prostate
      cancer (CaP) and benign prostatic hyperplasia (BPH) cultures. To perform
      microvessel density (MVD) counts on sections of BPH and CaP from the same
      prostatectomy specimens. SCOPE: Angiogenic cytokine expression was measured by
      immunoassays and in vitro angiostatin generating capacities assessed using
      immunoblotting. CaP and BPH tissue was immunostained using factor VIII antibody
      to determine MVD. CONCLUSIONS: Elements regulating angiogenesis are present in
      both primary cultures of CaP and BPH, suggesting that angiogenic ability is well
      established in the absence of carcinoma.

PMID- 12806372
TI  - Pentosan polysulfate decreases prostate smooth muscle proliferation and
      extracellular matrix turnover.
AB  - Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells
      and increased deposition of extracellular matrix (ECM). We recently found that
      pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle
      cells derived from vascular tissues. We examined smooth muscle cells cultured
      from human prostates and the effects of PPS on their growth and ECM production.
      Fragments of surgical prostatectomy specimens were diced, digested with
      collagenase (0.01%), and placed in culture medium supplemented with 20% fetal
      bovine serum. Outgrowths of elongated cells were characterized by light
      microscopic examination and immunohistochemical techniques by the presence of F
      actin, alpha-smooth muscle actin, and myosin, which is a characteristic of smooth
      muscle cells. Two independent isolates were propagated, and growth curves and ECM
      production were assessed in the presence and absence of PPS (10 or 100
      microg/ml). PPS decreased cell number beginning at day 1 and throughout the
      incubation period, up to 4 days. The amount of the ECM degradative enzymes,
      metallo-proteinases MMP-9 and MMP-2, was examined by zymography. PPS did not
      alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4 +/-
      17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by
      reverse zymography, increased 200% over control. The amount of alpha I type (IV)
      and alpha I type (I) collagen released in the supernatant, measured by ELISA,
      significantly decreased in PPS-treated cultures. In conclusion, we found that the
      administration of PPS decreased proliferation as well as ECM production in
      prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in
      the pathophysiology of BPH, PPS may have therapeutic potential.

PMID- 12806373
TI  - Pathologic characteristics of prostatic adenocarcinomas: a mapping analysis of
      Korean patients.
AB  - Pathologic characteristics of the prostatic adenocarcinoma in Koreans are not
      clear. We studied 132 cases of prostatectomy specimens using mapping analysis to
      discover the pathologic characteristics of the Korean prostatic adenocarcinoma.
      Mean values were as follows: serum prostate-specific antigen level (sPSA), 16.4
      ng/ml; tumor volume, 27.5%; size, 2.4 cm; Gleason score, 7.7; and p53 expression,
      9.8%. Rates of multifocal tumors and high-grade prostatic intraepithelial
      neoplasm (HPIN) were 33.3 and 65.2%. The Gleason score, tumor volume%, tumor size
      and sPSA were correlated with each other. Korean prostatic adenocarcinomas showed
      higher Gleason scores, lower rates of HPIN and multifocality, and lower p53
      expression in comparison to Western prostatic adenocarcinomas. These data may be
      a basis for pathologic characteristics of Korean prostatic adenocarcinoma that
      has now been increasing.

PMID- 12806374
TI  - Growth factor regulation of secreted matrix metalloproteinase and plasminogen
      activators in prostate cancer cells, normal prostate fibroblasts and normal
      osteoblasts.
AB  - We assessed the relative levels of secreted matrix metalloproteinases (MMPs) and
      plasminogen activators (PAs) in PC-3 cells, prostate fibroblasts and osteoblasts
      in the presence and absence of VEGF, TGF beta1 and bFGF. Fibroblasts and
      osteoblasts secreted more MMPs -1 and -2 than did PC-3 cells, while PC-3 s
      contributed the majority of PAs. MMP-1 expression was downregulated by
      transforming growth factor beta-1 (TGF beta1) treatment in prostate fibroblasts
      and upregulated by basic fibroblast growth factor (bFGF) in both stromal lines.
      In PC-3 cells, TGF beta1 and bFGF increased urokinase plasminogen activator
      secretion. TGF beta1 decreased tissue plasminogen activator secretion in all cell
      lines. Prostate cancer cells associated with fibroblasts or osteoblasts have a
      variety of MMPs and PAs to facilitate matrix degradation.

PMID- 12806375
TI  - PSA testing in general practice.
AB  - A questionnaire was sent to 400 general practitioners (GPs), concerning prostate
      specific antigen (PSA) screening. Regarding the indications for PSA testing, 80%
      of GPs test men with urinary tract symptoms, 65% test men with a positive family
      history, 62% test on patient request, and 21% test men with unrelated symptoms.
      When PSA is measured, 91% of GPs inform their patient, and 71% discuss the
      significance of an abnormal result. The mean age range for PSA testing was from
      50 years, without an upper age limit. The mode PSA threshold for referral was 6.6
      ng/ml. De facto PSA screening appears to be widely practised.

PMID- 12806376
TI  - Does the adjunct of ecographic contrast medium Levovist improve the detection
      rate of prostate cancer?
AB  - OBJECTIVES: To evaluate whether the adjunct of an ultrasound contrast medium
      improves the detection rate of prostate cancer. METHOD: In 34 patients, scheduled
      to undergo a trans-perineal extended prostate biopsy, we carried out a color
      Doppler ultrasound (CDU) of the prostate before and after i.v. injection of
      Levovist, an ultrasound contrast medium. Further bioptic samples were taken in
      the areas where a marked increase in vascularization was noticed. RESULTS: The
      overall diagnostic sensitivity, specificity and efficiency were respectively
      72.7, 56.2 and 62.9% for transrectal ultrasound (TRUS); 80, 56.2 and 65.3% for
      CDU and 88.8, 54.5 and 68% for CDU after Levovist injection; 66.5, 72.6 and 65.1%
      for digito-rectal examination (DRE); 100, 51.4 and 65.4% for total PSA; and 100,
      88.8 and 94.3% for PSA free/total. In the 16 patients with prostate carcinoma,
      the sensitivity of CDU after Levovist was 92.3, 66% for both DRE and TRUS, and
      80% for DRE plus TRUS. CONCLUSIONS: Considering the cost and the results obtained
      (high sensitivity and low specificity), a routine use of Levovist does not seem
      indicated in patients undergoing prostatic biopsy. An exception may be
      represented by patients with both negative DRE and TRUS.

PMID- 12806377
TI  - cPSA and fPSA elimination in African-American men.
AB  - In all, 22 African-American males undergoing radical prostatectomy for prostate
      adenocarcinoma had serum drawn for tPSA, cPSA, and total protein concentrations
      prior to, during, and after operation to determine the respective elimination
      rates. African-American cPSA was found to fit best a simple first-order
      exponential elimination kinetic, with a half-life of 44.6 h. fPSA followed a two
      compartment elimination with an alpha-phase elimination of 0.50 h and a beta
      phase half-life of 4.2 h. Our results suggest higher rates of elimination for
      both cPSA and fPSA in an African-American male population with respect to
      Caucasians and may account for differences in PSA values between races.

PMID- 12806378
TI  - Treatment and prognosis of patients with paraplegia or quadriplegia because of
      metastatic spinal cord compression in prostate cancer.
AB  - Metastatic spinal cord compression (MSCC) is a serious complication of metastatic
      prostate cancer (PCa). This study retrospectively evaluated patients who
      presented with paraplegia or quadriplegia because of MSCC of PCa. Of 847 patients
      with PCa who were treated between 1989 and 1998, 26 (3.1%) demonstrated
      paraplegia or quadriplegia because of MSCC. Characteristics, treatment efficacy,
      and prognosis of these patients were analyzed. In total, 15 cases became
      paraplegic despite androgen ablation therapy (Group I). Average time to
      paraplegia from initial hormonal treatment was 34 months. Out of nine cases who
      underwent radiation therapy (RT) to spinal lesions with/without chemotherapy, one
      patient became ambulatory. However, this patient subsequently had recurrent
      compression. Two cases had remission of paralysis. Two cases underwent
      laminectomy plus RT and in one case paralysis improved. MSCC was the first
      indication of PCa in 11 cases (Group II). Two cases underwent laminectomy plus
      hormone therapy and nine cases underwent hormone therapy alone. Four patients
      became ambulatory and two cases showed improved motor capacity. Average interval
      from paraplegia to death was 7.4 months in Group I and 27.1 months in Group II.
      However, there was no statistical difference in these two groups on disease
      specific survival from the start of initial treatment. It is difficult to recover
      the ability to walk if paraplegia or quadriplegia occurs in PCa patients although
      decompression surgery plus hormone therapy seemed to impair the prognosis. Stage
      M1 patients with paraplegia had survival rates as good as stage M1 patients
      without paralysis. This should encourage an aggressive treatment approach.
      However, for patients with hormone-independent disease there seems to be no
      effective treatment and prognosis is poor.

PMID- 12806379
TI  - Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases
      does not correlate with p53 overexpression.
AB  - Recent data have proposed that transcription of the KAI1 metastasis suppressor
      gene is directly mediated by p53 and that loss of KAI1 expression in advanced
      prostate cancer is simply due to loss of p53 function after mutation. To
      investigate this possibility, we have examined KAI1 mRNA (by in situ
      hybridisation) and p53 protein expression (by immunohistochemistry) as an
      indicator of wildtype or mutant p53, in a series of 77 paraffin-embedded prostate
      tissue samples, including post-mortem normal prostates (2), benign prostatic
      hyperplasia (10), localised cancer (grades 4-6, 25; grades 7-9, 21) and prostate
      derived bony metastases (19). Overall, we confirmed that expression of KAI1 mRNA
      decreased from normal tissue, through localised cancer to bony metastases
      (P=0.055, tending to significance), while levels of p53 staining significantly
      increased with cancer progression (P=0.046). These were consistent with the
      possibility that loss of p53 function might be responsible for loss of KAI1 mRNA.
      However, by close examination of KAI1 and p53 in adjacent tissue sections, we
      found no correlation between decreased levels of KAI1 mRNA and overexpression of
      p53 protein (P=0.497). In addition, high levels of KAI1 mRNA could be identified
      in samples irrespective of p53 staining. Our data suggest that mutation of p53 is
      independent of the loss of KAI1 mRNA, and do not support a role for p53 in
      regulating the expression of KAI1.

PMID- 12806380
TI  - Gyrus bipolar electrovaporization vs transurethral resection of the prostate: a
      randomized prospective single-blind trial with 1 y follow-up.
AB  - The Gyrus system uses bipolar electrocautery with saline irrigation to vaporize
      prostatic tissue and is compared to transurethral resection of the prostate
      (TURP) in a randomized prospective study with 1 y follow-up. Outcomes measured
      were fluid absorption, blood loss, period of catheterization, hospital stay,
      symptom scores, quality of life, flow rates, and post-void residual volumes at 3,
      6, and 12 months. All measured parameters were similar, although re
      catheterization rates were higher (30% vs 5%) in the Gyrus group. Clot evacuation
      rates were higher in the TURP group (19% vs 0%). The Gyrus device is safe and
      produces results that are similar to TURP at 1 y.

PMID- 12806382
TI  - Delayed life-threatening hemorrhage after transrectal prostate needle biopsy.
AB  - Minor hematochezia after transrectal ultrasound and prostate needle biopsy is
      well reported. We present a case report of a 64-yr-old man on aspirin and with
      poorly controlled hypertension who developed severe hematochezia requiring blood
      transfusion. The bleeding was stopped with digital compression. The literature on
      hemorrhagic complications after prostate needle biopsy is reviewed.

PMID- 12806381
TI  - Randomised crossover trial to assess the tolerability of LHRH analogue
      administration.
AB  - Luteinising hormone releasing hormone (LHRH) analogues are routinely used in the
      treatment of patients with advanced prostate cancer. This randomised crossover
      trial was conducted to compare patient comfort and tolerability between two
      commonly used LHRH analogues: goserelin acetate and leuprorelin acetate. A total
      of 50 patients were randomised into two groups, each receiving 6-monthly
      injections of leuprorelin acetate (a liquid presentation) and goserelin acetate
      (a depot pellet) and crossing over between treatments. Patients completed a
      simple visual analogue score for the discomfort felt from the injections. An
      analysis of variance model was used, and the results found that patients do
      tolerate leuprorelin acetate (0.589) better than goserelin acetate (1.343) (P <
      0.001, CI = 95%).

PMID- 12806383
TI  - Prostate cancer: the right treatment for the right patient. Amsterdam, 17-18
      January 2001.

PMID- 12806386
TI  - Conducting nanowires in insulating ceramics.
AB  - Low-dimensional structures, such as microclusters, quantum dots and one- or two
      dimensional (1D or 2D) quantum wires, are of scientific and technological
      interest due to their unusual physical properties, which are quite different from
      those in the bulk. Here we present a successful method for fabricating conducting
      nanowire bundles inside an insulating ceramic single crystal by using
      unidirectional dislocations. A high density of dislocations (10(9) cm(-2)) was
      introduced by activating a primary slip system in sapphire (alpha-Al2O3 single
      crystal) using a two-stage deformation technique. Plate specimens cut out from
      the deformed sapphire were then annealed to straighten the dislocations. Finally,
      the plates on which metallic Ti was evaporated were heat-treated to diffuse Ti
      atoms inside sapphire. As a result of this process, Ti atoms segregated along the
      unidirectional dislocations within about 5 nm diameter, forming unidirectional Ti
      enriched nanowires, which exhibit excellent electrical conductivity. This simple
      technique could potentially to be applied to any crystal, and may give special
      properties to commonly used materials.

PMID- 12806387
TI  - Atomic resolution of lithium ions in LiCoO2.
AB  - LiCoO2 is the most common lithium storage material for lithium rechargeable
      batteries, used widely to power portable electronic devices such as laptop
      computers. Operation of lithium rechargeable batteries is dependent on reversible
      lithium insertion and extraction processes into and from the host materials of
      lithium storage. Ordering of lithium and vacancies has a profound effect on the
      physical properties of the host materials and the electrochemical performance of
      lithium batteries. However, probing lithium ions has been difficult when using
      traditional X-ray and neutron powder diffraction techniques due to lithium's
      relatively low scattering power when compared with those of oxygen and transition
      metals. In the work presented here, we have succeeded in simultaneously resolving
      columns of cobalt, oxygen and lithium atoms in layered LiCoO2 battery material,
      using experimental focal series of LiCoO2 images obtained at sub-angstrom
      resolution in a mid-voltage transmission electron microscope. Lithium atoms are
      the smallest and lightest metal atoms, and scatter electrons only very weakly. We
      believe our observations of lithium to be the first by electron microscopy, and
      that they show promise for direct visualization of the ordering of lithium and
      vacancies in transition metal oxides.

PMID- 12806388
TI  - Bioassay of fenthion for possible carcinogenicity (CAS No. 55-38-9).
AB  - A bioassay of fenthion for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex and 50 mice of each sex were administered fenthion in the
      diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then observed
      for 0 to 2 additional weeks. Matched controls consisted of groups of 25 untreated
      animals of each species and sex. All surviving animals were killed at 103 to 105
      weeks. The mean body weights and the survival of the dosed animals were
      essentially unaffected by administration of the test chemical with the exception
      of the survival of the low-dose male mice, which was significantly lower than
      that of the corresponding matched control. Thus, most of the animals may have
      been able to tolerate higher doses. Sufficient numbers of animals in all groups
      of rats and mice were at risk for development of late-appearing tumors. In the
      male and female rats and the female mice, no tumors occurred at incidences that
      were significantly higher in dosed groups than in control groups. In the male
      mice, sarcomas, fibrosarcomas, or rhabdomyosarcomas of the integumentary system
      occurred at incidences that were dose related (P=0.043). In direct comparisons of
      the incidences of these tumors in the dosed groups with the incidence in the
      control group, the P values of 0.048 and 0.028 for the low- and high-dose groups,
      respectively, did not meet the Bonferroni criterion of P=0.025 for significance
      when multiple comparisons are made (controls 0/25, low-dose 7/49 or 14%, high
      dose 8/48 or 17%). However, the incidence of sarcomas and fibrosarcomas in
      historical-control male B6C3F1 mice used in bioassays of other chemicals tested
      at this laboratory was 7/435 (1.6%), and no rhabdomyosarcomas occurred in the
      historical-control male mice. It is concluded that under the conditions of this
      bioassay, fenthion was not carcinogenic for male or female F344 rats or for
      female B6C3F1 mice. The increased incidence of sarcomas, fibrosarcomas, and
      especially rhabdomyosarcomas of the integumentary system in the male B6C3F1 mice
      suggested that the test chemical was carcinogenic in these animals.

PMID- 12806389
TI  - Bioassay of 3-sulfolene for possible carcinogenicity (CAS No. 77-79-2).
AB  - A bioassay of 3-sulfolene for possible carcinogenicity was conducted using
      Osborne-Mendel rats and B6C3F1 mice. 3-Sulfolene in corn oil was administered by
      gavage, at either of two dosages, to groups of 50 male and 50 female animals of
      each species. The 78-week period of chemical administration was followed by an
      observation period of 33 weeks for the high dose female rats and low dose rats of
      both sexes. The last high dose male rat died in week 60. All treated groups of
      mice were observed for an additional 13 weeks following chemical administration.
      Initial dosage levels for the chronic bioassay were selected on the basis of a
      preliminary subchronic toxicity test. Subsequent dosage adjustments were made
      during the course of the chronic bioassay. The time-weighted average high and low
      doses of 3-sulfolene in the chronic study were respectively, 372 and 197
      mg/kg/day for male rats, 240 and 120 mg/kg/day for female rats, 622 and 311
      mg/kg/day for male mice and 768 and 384 mg/kg/day for the female mice. For each
      species, 20 animals of each sex were placed on test as vehicle controls. These
      animals were gavaged with corn oil at the same time that dosed animals were
      gavaged with the 3-sulfolene mixtures. Twenty animals of each sex were placed on
      test as untreated controls for each species. These animals were not intubated.
      There was a significant positive association between the administered dosages of
      3-sulfolene and mortality in both sexes of rats and mice. In all groups, except
      the high dose male rats and the high dose male and female mice, adequate numbers
      of animals survived sufficiently long to be at risk from late-developing tumors.
      There were no tumors in either sex of rats or mice for which a significant
      positive association could be established between chemical administration and
      incidence. Under the conditions of this bioassay, there was no evidence for the
      carcinogenicity of 3-sulfolene to Osborne-Mendel rats or B6C3F1 mice.

PMID- 12806390
TI  - Bioassay of formulated fenaminosulf for possible carcinogenicity (CAS No. 140-56
      7).
AB  - A bioassay of formulated fenaminosulf for possible carcinogenicity was conducted
      using Fischer 344 rats and B6C3F1 mice. Fenaminosulf was administered in the
      feed, at either of two concentrations, to groups of 50 male and 50 female animals
      of each species. The time-weighted average high and low dietary concentrations of
      fenaminosulf were, respectively, 0.10 and 0.05 percent for rats, 0.19 and 0.10
      percent for male mice, and 0.10 and 0.05 percent for female mice. After a 78-week
      period of compound administration, observation of the rats continued for up to an
      additional 31 weeks and observation of the mice continued for up to an additional
      19 weeks. Fifty male mice and 50 rats of each sex were placed on test as controls
      and fed only the basal diet. For female mice, 50 animals served as controls for
      the high dose group and 50 as controls for the low dose group. For female rats
      there was no significant association between fenaminosulf dosage and mortality
      and, if the 21 male rats that died in the first two weeks of the bioassay were
      excluded from consideration, the same was true for male rats. For both male and
      female mice there was a significant positive association between dosage and
      mortality. In all groups of both species, however, adequate numbers of animals
      survived sufficiently long to be at risk from late-developing tumors. No
      convincing, statistically significant positive associations were demonstrated
      between administration and the incidence of neoplasms in either sex of either
      species. An increased incidence of necrosis and mineralization of the tubular
      cells of the renal papilla occurred in treated rats and mice. These nonneoplastic
      lesions were not present in control animals of either species. Under the
      conditions of this bioassay, dietary administration of formulated fenaminosulf
      was not carcinogenic in either Fischer 344 rats or B6C3F1 mice.

PMID- 12806391
TI  - Bioassay of cupferron for possible carcinogenicity (CAS No. 135-20-6).
AB  - A bioassay of cupferron for possible carcinogenicity was conducted using Fischer
      344 rats and B6C3F1 mice. Cupferron was administered in the feed, at either of
      two concentrations, to groups of 49 or 50 male and 50 female animals of each
      species. The time-weighted average high and low dietary concentrations of
      cupferron were, respectively, 0.30 and 0.15 percent for male and female rats, and
      0.4 and 0.2 percent for male and female mice. After a 78-week period of compound
      administration, observation of the rats continued for an additional period of up
      to 28 weeks and observation of the mice continued for an additional period of up
      to 18 weeks. For each species, 50 animals of each sex were placed on test as
      controls and fed only the basal diet. Among both sexes of rats and mice there was
      a significant positive association between the dose of cupferron administered and
      mortality; however, in all groups of animals sufficient numbers survived long
      enough to establish the carcinogenicity of this compound. There were significant
      positive associations between the concentrations of cupferron administered to
      male and female rats and the incidences of: squamous-cell carcinomas of the
      forestomach, hepatocellular carcinomas and neoplastic nodules, and
      hemangiosarcomas. When a binomial distribution and a spontaneous incidence rate
      corresponding to the appropriate historical control incidence were assumed, the
      incidences of auditory sebaceous gland neoplasms in female rats and female mice
      were significant. There were significant positive associations between the
      concentrations administered and the incidences of hepatocellular carcinomas in
      female mice, the incidences of hemangiosarcomas in both sexes of mice, and the
      incidence of Harderian gland adenomas in both sexes of mice. Under the conditions
      of this bioassay cupferron was carcinogenic in Fischer 344 rats, causing
      hemangiosarcomas, hepatocellular carcinomas, and squamous-cell carcinomas of the
      forestomach in males and females as well as carcinomas of the auditory sebaceous
      gland in females. The chemical was also carcinogenic in B6C3F1 mice, causing
      hemangiosarcomas in males and hepatocellular carcinomas, carcinomas of the
      auditory sebaceous gland, a combination of hemangiosarcomas and hemangiomas, and
      adenomas of the Harderian gland in females.

PMID- 12806392
TI  - Bioassay of phenazopyridine hydrochloride for possible carcinogenicity.
AB  - A bioassay of phenazopyridine hydrochloride for possible carcinogenicity was
      conducted by administering the test chemical in feed to Fischer 344 rats and
      B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered
      phenazopyridine hydrochloride at one of the following doses, either 3,700 or
      7,500 ppm for rats and either 600 or 1,200 ppm for mice. The rats were
      administered the chemical for 78 weeks, then observed for 26 or 27 additional
      weeks; the mice were administered the chemical for 80 weeks, then observed for 25
      27 additional weeks. Matched controls consisted of 15 untreated rats and 15
      untreated mice of each sex. All surviving rats were killed at 104 or 105 weeks,
      all surviving mice at 105-107 weeks. Mean body weights of the dosed rats and mice
      of each sex were consistently lower than those of corresponding control animals,
      and the depressions in mean body weight were dose related. Mortality in the
      groups of rats and mice did not, however, show dose-related trends, and
      sufficient numbers of animals of both dosed and control groups were at risk for
      the development of late-appearing tumors. In male rats, adenomas or
      adenocarcinomas of the large intestine (colon or rectum) occurred at incidences
      having a significant dose-related trend (P=0.015). The direct comparison of the
      incidences in each of the dosed groups with that in the control group was not
      significant (controls 0/14, low-dose 4/34, high-dose 8/35). In the females, 3/33
      low-dose and 5/32 high-dose animals, but no control animals, had this tumor. In
      addition, sarcomas were observed in the colon of one low-dose male and one high
      dose female. The laboratory historical records showed no incidence of adenomas or
      adenocarcinomas of the large intestine in 260 females and only one adenomatous
      polyp in 260 males. Assuming a spontaneous incidence of 1/261 (0.038%) and a
      binomial distribution of such tumors, the occurrence seen in the male and female
      high-dose groups are both significantly (P<0.001) different from the expected
      value. Thus, these tumors are considered to be related to administration of the
      test chemical. In female mice, the combined incidence of hepatocellular adenomas
      and carcinomas showed a significant dose-related trend (P=0.002), and the
      incidence in the high-dose group was significant (P=0.003) when compared with
      that in the control group (controls 2/15, low-dose 11/34, high-dose 19/32). The
      incidence of hepatocellular carcinomas, considered alone, also was significant in
      female mice, showing a dose-related trend (P=0.010) and a P value of 0.039 for
      the comparison of the high-dose group with the control group. In the males, the
      combined incidence of hepatocellular adenomas and carcinomas was not significant.
      It is concluded that under the conditions of this bioassay, phenazopyridine
      hydrochloride was carcinogenic in Fischer 344 rats, inducing adenocarcinomas of
      the colon in both males and females. Although phenazopyridine hydrochloride was
      not carcinogenic in male B6C3F1 mice, the chemical was carcinogenic in females,
      inducing hepatocellular adenomas and carcinomas.

PMID- 12806393
TI  - Bioassay of dl-menthol for possible carcinogenicity.
AB  - A bioassay of dl-menthol for possible carcinogenicity was conducted by
      administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
      Groups of 50 rats of each sex and 50 mice of each sex were administered dl
      menthol at one of the following doses, either 3,750 or 7,500 ppm for the rats and
      either 2,000 or 4,000 ppm for the mice, for 103 weeks, then observed for 1 or 2
      additional weeks. Matched controls consisted of 50 untreated rats of each sex and
      50 untreated mice of each sex. All surviving rats were killed at 105 weeks and
      all surviving mice at 104 weeks. Mean body weights of dosed rats and mice were
      only slightly lower than those of corresponding controls. No other clinical signs
      related to administration of the dl-menthol were noted in the dosed groups of
      animals. A dose-related trend in mortality was observed only in the female mice.
      Survival at the end of the bioassay was at least 62% in all dosed and control
      groups of animals of each species, and sufficient numbers of animals were at risk
      for the development of late-appearing tumors. In male rats, no tumors occurred at
      incidences which were considered to be related to the administration of dl
      menthol. In female rats, no tumors occurred at higher incidences in the dosed
      groups than in the control groups. Fibroadenomas of the mammary gland occurred at
      lower incidences in the low-dose (10/49) and high-dose (7/49) groups than in the
      control group (20/50), and alveolar/bronchiolar adenomas or carcinomas of the
      lung occurred only in the controls (3/50). In mice of either sex, no tumors
      occurred in dosed groups at incidences that were significantly different from
      those for corresponding control groups. It is concluded that under the conditions
      of this bioassay, dl-menthol was not carcinogenic for either Fischer 344 rats or
      B6C3F1 mice.

PMID- 12806394
TI  - Bioassay of titanium dioxide for possible carcinogenicity.
AB  - A bioassay of titanium dioxide for possible carcinogenicity was conducted by
      administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
      Groups of 50 rats of each sex and 50 mice of each sex were administered titanium
      dioxide in the diet at one of two doses, either 25,000 or 50,000 ppm, for 103
      weeks and then observed for 1 additional week. Matched controls consisted of 50
      untreated rats of each sex and 50 untreated mice of each sex. All surviving rats
      and mice were killed at 104 weeks. Administration of the titanium dioxide had no
      appreciable effect on the mean body weights of rats or mice of either sex. With
      the exception of white feces, there was no other clinical sign that was judged to
      be related to the administration of titanium dioxide. Survival of the rats and
      the male mice at the end of the bioassay was not affected by the test chemical;
      mortality in female mice was dose related. Sufficient numbers of dosed and
      control rats and mice of each sex were at risk for development of late-appearing
      tumors. In the female rats, C-cell adenomas or carcinomas of the thyroids
      occurred at incidences that were dose related (P=0.013), but were not high enough
      (P=0.043 for direct comparison of the high-dose group with the control group) to
      meet the level of P=0.025 required by the Bonferroni criterion (controls 1/48,
      low-dose 0/47, high-dose 6/44). Thus, these tumors of the thyroid were not
      considered to be related to the administration of the test chemical. In male and
      female mice, no tumors occurred in dosed groups at incidences that were
      significantly higher than those for corresponding control groups. It is concluded
      that under the conditions of this bioassay, titanium dioxide was not carcinogenic
      by the oral route for Fischer 344 rats or B6C3F1 mice.

PMID- 12806395
TI  - Bioassay of coumaphos for possible carcinogenicity.
AB  - A bioassay of coumaphos for possible carcinogenicity was conducted by
      administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of
      50 rats of each sex and 50 mice of each sex were administered the coumaphos in
      the diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then
      observed for 0-1 additional weeks. Matched controls consisted of groups of 25
      untreated animals of each species and sex. All surviving animals were killed at
      103-105 weeks. Mean body weights of the dosed female rats were lower than those
      of corresponding controls, while mean body weights of dosed male rats and of
      dosed male and female mice were essentially unaffected. No clinical signs that
      are typical of organophosphorus poisoning were reported in either rats or mice.
      Survival of the rats and mice was not affected by administration of the test
      chemical. The test animals may have been able to tolerate higher doses.
      Sufficient numbers of animals in all groups of the rats and mice were at risk for
      the development of late-appearing tumors. In both rats and mice, no tumors
      occurred in the dosed groups of either sex at incidences that were significantly
      higher than those in corresponding control groups. It is concluded that under the
      conditions of this bioassay, coumaphos was not carcinogenic for either F344 rats
      or B6C3F1 mice.

PMID- 12806396
TI  - Bioassay of 3-(chloromethyl) pyridine hydrochloride for possible carcinogenicity.
AB  - A bioassay of 3-(chloromethyl)pyridine hydrochloride for possible carcinogenicity
      was conducted by administering the test chemical by gavage to Fischer 344 rats
      and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered 3
      (chloromethyl)pyridine hydrochloride in a vehicle of distilled water three times
      per week at one of the following doses, either 75 or 150 mg/kg body weight for
      the rats and either 100 or 200 mg/kg body weight for the mice. The low-dose rats
      were dosed for 103 weeks and the low-dose mice for 102 weeks. Because of early
      deaths in the high-dose animals, the high-dose rats were dosed for only 83 weeks
      and the high-dose mice for only 81 weeks. Controls consisted of groups of 20 rats
      and 20 mice of each sex which were administered the vehicle only for 104 weeks.
      All surviving rats and mice were killed at 104 weeks. Mean body weights of the
      male and female rats were lower in the dosed groups than in the corresponding
      control groups, and the depressions in weight were dose related. At the
      termination of the administration of the test chemical to the high-dose groups of
      rats, the mean body weights of these groups recovered rapidly. The mean body
      weights of the male mice were unaffected by the administration of the chemical;
      those of the females were only slightly affected. Mortality was generally higher
      in the dosed groups of rats and mice than in the corresponding control groups and
      was dose related in all tests except those using the female mice; however,
      sufficient numbers of animals of each species and sex were at risk for the
      development of late-appearing tumors. In rats, proliferative squamous-cell
      lesions of the forestomach were observed in the dosed males (carcinomas: high
      dose 1/50; papillomas: low-dose 1/47; high-dose 2/50; hyperplasias: low-dose
      1/47, high-dose 2/50) and the dosed females (carcinomas: high-dose 1/48), but not
      in the male or female vehicle controls. The results of the Fischer exact test
      were not significant for squamous-cell papillomas or carcinomas. However,
      comparison of the incidence of these tumors in the high-dose males with that in
      99 historical vehicle controls shows that the probability that three or more such
      tumors did not occur by chance, given that none have been observed in the
      controls in this laboratory, is P=0.014. In mice, squamous-cell papillomas or
      carcinomas of the forestomach occurred in the low- and high-dose groups of each
      sex, but not in the corresponding control groups. The incidence in the high-dose
      males was significantly higher (P=0.025) than that in the control males (males:
      vehicle controls 0/19; low-dose 2/43; high dose 10/47 [21%]; females: vehicle
      controls 0/19, low-dose 1/45, high-dose 5/48 [10%]). Comparison of the incidences
      of these tumors in the high-dose males and females with those observed in the
      corresponding control groups of 100 historical vehicle controls of each sex shows
      that the probability that their occurrence was not due to chance is P<0.001.
      Also, a life-table analysis of the incidence in males indicated a significant
      (P=0.003) increase in tumors over the period of observation (58 weeks to 104
      weeks) in relation to an increase in dose. Although the incidence of squamous
      cell papillomas and carcinomas in male and female rats was significant only in
      males compared with historical vehicle controls, these tumors are of the same
      type as those appearing at the same site in male and female mice. Because these
      tumors are rare and not found in controls, and because they were found in dosed
      animals of both species, they are considered to be related to administration of
      the test chemical by gavage. It is concluded that under the conditions of this
      bioassay, 3-(chloromethyl)pyridine hydrochloride was carcinogenic in male Fischer
      344 rats and B6C3F1 mice of both sexes, producing papillomas and carcinomas at
      the site of topical application, the stomach.

PMID- 12806397
TI  - Bioassay of 4-amino-2-nitrophenol for possible carcinogenicity.
AB  - A bioassay of 4-amino-2-nitrophenol for possible carcinogenicity was conducted by
      administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
      Groups of 50 rats and 50 mice of each sex were administered 4-amino-2-nitrophenol
      at one of two doses, either 1,250 or 2,500 ppm, for 103 weeks. Matched controls
      consisted of groups of 20 untreated rats and 20 untreated mice of each sex. All
      dosed and matched-control groups of each species and sex were killed at 105
      weeks. Mean body weights of dosed rats of each sex were not appreciably affected
      by administration of the 4-amino-2-nitrophenol, and mean body weights of dosed
      mice of each sex were only slightly lower than those of corresponding matched
      controls. Survival of neither rats nor mice was affected by the test chemical,
      and sufficient numbers of animals in dosed and control groups were at risk for
      the development of late-appearing tumors. Since both male and female mice
      receiving 4-amino-2-nitrophenol had little or no depression in mean weights and
      their survival was comparable to that of controls, they may have been able to
      tolerate a higher dose. In rats, transitional-cell carcinomas of the urinary
      bladder showed a dose-related trend in the males (P<0.001) and occurred at a
      significantly higher incidence (P=0.018) in the high-dose males than in the
      matched-control males (controls 0/15, low-dose 0/46, high-dose 11/39 [28%]).
      Carcinomas of the bladder also occurred in one low-dose female and two high-dose
      females, but in none of the control females. Transitional-cell papillomas of the
      bladder occurred in two additional high-dose males, and transitional-cell
      hyperplasia of the bladder occurred in four additional high-dose males, but
      neither lesion occurred in control males. No tumors of the bladder were found
      among 220 male and 220 female historical-control rats at this laboratory. In
      mice, no tumors occurred in dosed groups of males or females at incidences that
      were significantly higher than those in the corresponding matched-control groups.
      Deposition of pigment occurred in the lamina propria of the small intestine in at
      least 91% of the animals in the dosed groups of rats and in at least 89% of the
      animals in the dosed groups of mice, but in none of the control groups of either
      species. It is concluded that under the conditions of the bioassay, 4-amino-2
      nitrophenol was carcinogenic for male Fischer 344 rats, inducing transitional
      cell carcinomas of the urinary bladder; the transitional-cell carcinomas of the
      urinary bladder observed in three dosed female rats may also have been associated
      with administration of the 4-amino-2-nitrophenol. The test chemical was not
      carcinogenic for male or female B6C3F1 mice at the doses tested.

PMID- 12806398
TI  - Bioassay of 3-amino-9-ethylcarbazole hydrochloride for possible carcinogenicity.
AB  - A bioassay of 3-amino-9-ethylcarbazole (hydrochloride) for possible
      carcinogenicity was conducted by administering the test chemical in feed to
      Fischer 344 rats and B6C3F1 mice. Both the free amine and the hydrochloride salt
      were used. Groups of 50 rats of each sex and 50 mice of each sex were
      administered the test chemical at one of two doses, either 800 or 2,000 ppm for
      rats and either 800 or 1,200 ppm for mice, for 78 weeks. The rats were then
      observed for an additional 26-29 weeks, and the mice for an additional 16-17
      weeks. Controls consisted of groups of 50 untreated rats of each sex and 50
      untreated mice of each sex; separate controls were used for the groups of animals
      administered the different doses. All surviving rats were killed at 104-110
      weeks; all surviving mice were killed at 94-97 weeks. Since the suppliers of the
      low-dose rats and mice differed from those of the corresponding low-dose
      controls, while the suppliers for the high-dose rats and mice were the same as
      those of the corresponding high-dose controls, comparisons of the high-dose
      groups with their corresponding controls were the most appropriate. Furthermore,
      since the low-dose animals did not receive the same regimen of administration of
      the test compound as that received by the high-dose animals, and since tests
      using the low-dose groups were not performed concurrently with those using the
      high-dose groups, analyses of the dose-related trends were not possible. Although
      the interpretation of results of the study was based primarily on comparisons of
      high-dose groups with their respective controls, the results obtained with the
      low-dose groups, regardless of the indicated complicating factors, supported the
      interpretation. Neoplasms of the liver were observed in significant incidences in
      rats and mice of both sexes. In male rats, hepatocellular carcinomas alone were
      significantly higher (P</=0.020) in both the low- and high-dose groups. When
      neoplastic nodules of the liver were combined with hepatocellular carcinomas, the
      combination occurred at significant incidences (P</= 0.012) in the low- and high
      dose male rats and in the high-dose female rats (males: low-dose controls 0/36,
      low-dose 12/42; high-dose controls 1/48, high-dose 22/48; females: high-dose
      controls 0/50, high-dose 6/48). Hepatocellular carcinomas alone similarly
      occurred at significant incidences (P<0.001) in the low- and high-dose male and
      female mice (males: low-dose controls 7/48, low-dose 32/44; high-dose controls
      6/44, high-dose 41/49; females: low-dose controls 1/47, low-dose 36/43; high-dose
      controls 1/45; high-dose 43/49). Papillomas or carcinomas of the integumentary
      system occurred at significant incidences (P</= 0.013) in both the low- and high
      dose male rats (low-dose controls 0/36, low-dose 8/44; high-dose controls 0/48,
      high-dose 6/48); these tumors also occurred in low- and high-dose female rats,
      but not at incidences high enough to be statistically significant (low-dose
      control 0/39, low-dose 4/44; high-dose controls 0/50, high-dose 4/49). Carcinomas
      of the Zymbal's glands of the ear occurred at significant incidences (P</= 0.045)
      in the low- and high-dose male and female rats (males: low-dose controls 0/36,
      low-dose 5/44; high-dose controls 0/48, high-dose 7/48; females: low-dose
      controls 0/39, low-dose 10/44; high-dose controls 0/50, high-dose 12/49). These
      tumors were first observed as early as week 47 on study. Adenocarcinomas of the
      uterus or endometrium occurred at a significant incidence (P=0.002) only in the
      high-dose female rats (high-dose controls 1/50, high-dose 11/49); these tumors
      also occurred in the low-dose females, but not at an incidence high enough to be
      statistically significant (low-dose controls 4/38, low dose 11/43). It is
      concluded that under the conditions of this bioassay, 3-amino-9-ethylcarbazole
      (hydrochloride) was carcinogenic for the liver, inducing hepatocellular
      carcinomas in Fischer 344 rats and B6C3F1 mice of both sexes. Other tumors
      induced in the rats were carcinomas or papillomas of the integumentary system in
      males, carcinomas of the Zymbal's gland of the ear in males and females, and
      adenocarcinomas of the uterus.

PMID- 12806399
TI  - Bioassay of hydrazobenzene for possible carcinogenicity.
AB  - A bioassay of technical-grade hydrazobenzene for possible carcinogenicity was
      conducted using Fischer 344 rats and B6C3F1 mice. Hydrazobenzene was administered
      in the feed, at either of two concentrations, to groups of 50 male and 47 to 50
      females animals of each species. The time-weighted average dietary concentrations
      used in the rat bioassay were 0.008, 0.03, 0.004, and 0.01 percent for low dose
      males, high dose males, low dose females, and high dose females, respectively.
      The time-weighted average dietary concentrations used in the mouse bioassay were
      0.008, 0.04, 0.004, and 0.04 percent for low dose males, high dose males, low
      dose females, and high dose females, respectively. After a 78-week period of
      compound administration, observation of the rats continued for an additional 28
      to 30 weeks and observation of the mice continued for an additional 17 or 18
      weeks. For each species, 47 to 50 animals of each sex were placed on test as
      controls. In both, species, adequate numbers of animals in all groups survived
      sufficiently long to be at risk from late-appearing tumors. The incidence of
      hepatocellular carcinomas was significantly increased in dosed male rats and the
      incidence of neoplastic nodules of the liver was significantly increased in dosed
      female rats. A significant increase in the combined incidence of squamous-cell
      carcinomas or squamous-cell papillomas of the Zymbal's gland, the ear canal, or
      the skin of the ear was observed among high dose male rats. A significant
      increase in mammary adenocarcinomas was observed among dosed female rats. The
      incidence of hepatocellular carcinomas was significantly increased among female
      mice, but no significant increase in liver tumors was observed among male mice.
      Under the conditions of this bioassay, hydrazobenzene was carcinogenic to Fischer
      344 rats of both sexes, causing increased incidences of hepatocellular carcinoma
      and Zymbal's gland squamous-cell neoplasms in male rats, neoplastic nodules of
      the liver in female rats, and mammary adenocarcinomas in female rats.
      Hydrazobenzene was also carcinogenic to female B6C3F1 mice, causing an increased
      incidence of hepatocellular carcinomas. The compound was not carcinogenic to male
      B6C3F1 mice.

PMID- 12806400
TI  - Bioassay of clonitralid for possible carcinogenicity.
AB  - A bioassay for possible carcinogenicity of clonitralid was conducted using
      Osborne-Mendel rats and B6C3F1 mice. Clonitralid was administered in the feed, at
      either of two concentrations, to groups of 50 male and 50 female animals of each
      species. Twenty animals of each sex and species were placed on test as controls.
      The time-weighted average high and low dietary concentrations of clonitralid
      were, respectively, 28,433 and 14,216 ppm for rats and 549 and 274 ppm for mice.
      After a 78-week period of compound administration, there was an additional
      observation period of 32 to 33 weeks for rats and 13 to 14 weeks for mice.
      Adequate numbers of male rats, female rats, and female mice survived long enough
      to be at risk from late-developing tumors. Because of inadequate survival among
      male mice, however, results obtained from observation of the male mouse groups
      cannot be considered conclusive. The incidences of mammary adenocarcinomas in
      treated female rats were not significantly higher than the incidences observed in
      control female rats. However, the incidences of this lesion in dosed female rats
      were greater than or equal to 22 percent, while the highest incidence observed in
      15 control groups at this laboratory was only 10 percent with a mean incidence of
      2.6 percent. The occurrence in high dose female rats (2/45) of carcinomas in the
      glandular portion of the stomach with metastases to other sites was not
      statistically significant. This incidence, however, is much greater than the
      historical control incidence and suggests an association between administration
      of clonitralid and the development of these tumors. No statistically significant
      increased tumor incidences were observed among male rats or mice of either sex
      dosed with clonitralid. Under the conditions of this bioassay, there was no
      convincing evidence that clonitralid was carcinogenic to Osborne-Mendel rats or
      to female B6C3F1 mice. Poor survival of male mice did not permit an evaluation of
      carcinogenicity in these animals.

PMID- 12806401
TI  - Bioassay of dicofol for possible carcinogenicity.
AB  - A bioassay of technical-grade dicofol for possible carcinogenicity was conducted
      using Osborne-Mendel rats and B6C3F1 mice. Dicofol was administered in the feed,
      at either of two concentrations, to groups of 50 males and 50 females of each
      species. The high and low time-weighted average concentrations of dicofol were,
      respectively, 942 and 471 ppm for male rats, 760 and 380 ppm for female rats, 528
      and 264 ppm for male mice, and 243 and 122 ppm for female mice. For each species,
      20 animals of each sex were placed on test as controls. The period of compound
      administration was 78 weeks, followed by 34 weeks of observation in rats and 14
      or 15 weeks in mice. There was no statistically significant positive association
      between dietary concentration and mortality in either sex or species.
      Hepatocellular carcinomas in dosed male mice were the only neoplasms that
      occurred in any dosed group of either species in statistically significant
      increased incidences when compared to controls. The Cochran-Armitage test as well
      as the Fischer exact test for both the high and low dose groups supported the
      association between compound administration and increased incidences of this
      tumor in the male mice. No increase in hepatocellular carcinomas was observed in
      dosed female mice. Under the conditions of this bioassay, technical-grade dicofol
      was carcinogenic in male B6C3F1 mice, causing hepatocellular carcinomas. No
      evidence for carcinogenicity was obtained for this compound in Osborne-Mendel
      rats of either sex or in female B6C3F1 mice.

PMID- 12806402
TI  - Bioassay of o-anisidine hydrochloride for possible carcinogenicity.
AB  - A bioassay of o-anisidine hydrochloride for possible carcinogenicity was
      conducted by administering the test chemical in feed to Fischer 344 rats and
      B6C3F1 mice. Groups of 55 rats of each sex and 55 mice of each sex were
      administered o-anisidine hydrochloride at one of the following doses, either
      5,000 or 10,000 ppm for rats and either 2,500 or 5,000 ppm for mice, for 103
      weeks, then observed for 1 or 2 additional weeks. Controls consisted of groups of
      55 untreated rats of each sex and 55 untreated mice of each sex. All surviving
      rats were killed at 103-107 weeks, and all surviving mice at 104 or 105 weeks.
      Mean body weights of the dosed male and female rats and mice were lower than
      those of the corresponding controls throughout the bioassay. Bloody exudates and
      stained fur in the urogenital area were noted in many dosed animals. Sufficient
      numbers of animals were at risk in the mice, but not in the rats, for development
      of late-appearing tumors; however, survival in the rats was 80% or more at week
      52. Transitional-cell carcinomas or papillomas of the urinary bladder occurred at
      statistically significant incidences (P<0.001) in the low- and high-dose groups
      of rats (males: controls 0/51, low-dose 52/54, high-dose 52/52; females: controls
      0/49, low-dose 1/51, high-dose 22/50); the incidences also had significant dose
      related trends (P<0.001) in both species. These lesions were observed as early as
      week 36 in female rats, week 40 in male rats, and week 45 in male mice.
      Transitional-cell carcinomas of the pelvis of the kidney occurred with a
      significant dose-related trend (P=0.005) in the male rats, and the incidence in
      the high-dose group was significantly higher (P=0.006) than that in the control
      group (controls 0/53, low-dose 3/55, high-dose 7/53); all rats having this tumor
      also has a transitional-cell carcinoma of the urinary bladder. Only one animal in
      the control groups of rats or mice had any tumor of the urinary system (a
      transitional-cell papilloma of the pelvis of the kidney in a male mouse).
      Follicular-cell tumors of the thyroid (carcinomas, cystadenocarcinomas, adenomas,
      cystadenomas, and papillary cystadenomas) occurred at statistically significant
      incidences (P</= 0.005) in low- and high-dose groups of male rats (controls 0/53,
      low-dose 7/40, high-dose 6/40); the incidences also had a dose-related trend
      (P=0.009). These tumors did not occur at significant incidences in dosed groups
      of female rats. It is concluded that under the conditions of this bioassay, o
      anisidine hydrochloride was carcinogenic for Fischer 344 rats and B6C3F1 mice,
      inducing transitional-cell carcinomas or papillomas of the bladder in both rats
      and mice and in both sexes of each species, transitional-cell carcinomas of the
      pelvis of the kidney in male rats, and follicular-cell tumors of the thyroid in
      male rats.

PMID- 12806403
TI  - Lessons from surveillance; solving the pertussis puzzle.

PMID- 12806405
TI  - A pertussis epidemic in NSW: how epidemiology reflects vaccination policy.

PMID- 12806404
TI  - Has pertussis increased in NSW over the past decade? An evaluation using
      hospitalisation and mortality data versus notifications 1988-2002.

PMID- 12806406
TI  - Do variations in pertussis notifications reflect incidence or surveillance
      practices? A comparison of infant notification rates and hospitalisation data in
      NSW.

PMID- 12806408
TI  - Australia's national serosurveillance program.

PMID- 12806407
TI  - Differences in the epidemiology of invasive pneumococcal disease, metropolitan
      NSW, 1997-2001.

PMID- 12806409
TI  - Vaccine-preventable diseases and vaccination coverage in Australia, 1999-2000.

PMID- 12806410
TI  - Immunisation coverage: Australia 2001.

PMID- 12806411
TI  - FactSheet: hand, foot and mouth disease.

PMID- 12806412
TI  - Communicable diseases report, NSW: April-May 2003.

PMID- 12806413
TI  - Celebrating the past; awakening the future: the NSW Public Health Forum
      highlights public health successes in NSW.

PMID- 12806414
TI  - The Sydney Olympics: a win for public health.

PMID- 12806415
TI  - Reducing tobacco consumption.

PMID- 12806416
TI  - The decline in gun deaths.

PMID- 12806417
TI  - Building the infrastructure for public health.

PMID- 12806418
TI  - Reducing lead exposure in children in Broken Hill.

PMID- 12806419
TI  - Halving deaths from cervical cancer.

PMID- 12806420
TI  - Containing HIV in NSW: a world class success.

PMID- 12806421
TI  - May 1999 NSW Drug Summit.

PMID- 12806422
TI  - FactSheet: Severe Acute Respiratory Syndrome (SARS).

PMID- 12806423
TI  - Communicable Diseases Report, NSW: March 2003.

PMID- 12806424
TI  - Neutral sphingomyelinase as a target for drug design.
AB  - The sphingolipid ceramide is an important second messenger assumed to be involved
      in fundamental processes, including proliferation, differentiation and growth
      arrest, as well as the induction of apoptosis. Ceramide is generated in a
      ubiquitous and evolutionarily conserved signaling pathway called the
      sphingomyelin pathway, through the action of distinct isoforms of
      sphingomyelinases. An improved understanding of sphingomyelinase-dependent
      signaling may offer significant insights into the regulation of physiological and
      pathological processes and may finally provide novel strategies and new targets
      for pharmacological intervention (e.g., in inflammatory responses,
      neurodegenerative diseases and cancer). This article summarizes the current
      knowledge of the role of neutral sphingomyelinase (N-SMase) in cell signaling
      pathways, and its potential meaning, and demonstrates the opportunity of a
      specific inhibition of N-SMases as a novel therapeutic target.

PMID- 12806425
TI  - Role of chemokines/chemokine receptor systems in cartilage degradation.
AB  - The underlying mechanism of the degradation of articular cartilage is an
      imbalance between anabolic and catabolic pathways, which are under the control of
      cytokines. Chemokines are a novel class of small cytokines and have a wide range
      of effects in many different cell types, both inside and outside of the immune
      system. Their actions are mediated by a family of 7-transmembrane G-protein
      coupled receptors. Recent studies have demonstrated that chondrocytes co-express
      chemokines and their receptors, and that the interaction of chemokines with their
      receptors results in the release of cartilage matrix-degrading proteinases, and
      affect proteoglycan metabolism in chondrocytes. These data reveal a catabolic
      pathway primed by chemokine/chemokine receptor system in articular cartilage,
      thus proposing a novel therapeutic approach against cartilage destruction in
      arthropathy.

PMID- 12806426
TI  - Rho-kinase as a potential target for the treatment of erectile dysfunction.
AB  - Erectile dysfunction is a condition that is estimated to affect more than 30
      million men in the United States alone. The prevalence of erectile dysfunction is
      increased with age and is often secondary to diseases such as depression,
      hypertension and diabetes. Causes of erectile dysfunction include physical injury
      to the cavernosum and abnormal cerebral and peripheral nervous system
      functioning. However, many cases of erectile dysfunction are the result of
      dysfunctional signaling in the cavernosal vasculature. This article will detail
      the important role of a vasoconstrictor mechanism mediated by the small G-protein
      RhoA and a downstream serine/threonine kinase, Rho-kinase, in the maintenance of
      penile flaccidity. Recent evidence demonstrates that inhibition of endogenous Rho
      kinase initiates an erectile response in an in vivo rat model. These initial
      findings introduce a novel potential therapeutic approach for the treatment of
      erectile dysfunction.

PMID- 12806427
TI  - Histamine and the classic antihistamines.
AB  - The first steps leading to the recognition of histamine's biological activity
      were taken in 1907. The existence of histamine in the body was finally recognized
      by 1910, and many researchers were keen to establish its physiological role,
      especially with regard to clinical shock and hypersensitivity reactions. The
      Pasteur Institute succeeded in finding a drug that would act as a biochemical
      tool to block the actions of histamine in the body and thereby reveal more about
      its physiological role, but none of its compounds was potent or safe enough to
      use in humans. Developments over the following years were made in producing
      compounds safe enough for clinical application in the treatment of allergies, and
      variations in these early antihistamines led to other uses. The first of the
      ethanolamine-based antihistamines marketed in the 1940s were used as antiallergy
      drugs, motion sickness remedies and antiemetics. The problem of drowsiness
      induced by antihistamines was overcome by the 1980s with drugs such as
      terfenadine and acrivastine.

PMID- 12806428
TI  - The changing role of drug metabolism and pharmacokinetics.
AB  - The Pharmacokinetics and Drug Metabolism for Chemists meeting held November 13,
      2001, in Stevenage, U.K., provided an interesting overview of how the drug
      metabolism and pharmacokinetics (DMPK) field has developed and the increasing
      importance, now recognized by most major companies, of obtaining DMPK data early
      in the drug discovery process. In addition to the repositioning of DMPK as a
      critical element of drug discovery, it was also made clear that the future should
      see fewer development compounds terminated because of DMPK factors.

PMID- 12806429
TI  - Pharmacology down under in 2001.
AB  - Every December, pharmacologists and toxicologists of Australia and New Zealand
      gather for the Australasian Society of Clinical and Experimental Pharmacologists
      and Toxicologists annual scientific meeting. The 2001 meeting highlighted the
      areas of cardiovascular research and neurodegeneration and neuroprotection.
      Cardiovascular researchers are investigating such areas as drugs for pulmonary
      hypertension, links between superoxide dismutase and cardiovascular disease, and
      angiogenesis. There was considerable discussion as to why neuroprotective agents
      that are so promising in animals fail in the clinic. Potential new agents and new
      targets for neuroprotection were also considered.

PMID- 12806430
TI  - Oligonucleotide inhibition of Fas as a potential treatment strategy in human
      liver disease.
AB  - Fas (CD95 or APO-1) is a member of tumor necrosis factor receptor (TNFR) family.
      Upon activation, by either binding with Fas ligand or self-aggregation, Fas
      signaling leads to cell apoptosis. Fas is believed to play a role in T-cell- and
      B-cell-mediated cytotoxicity and depletion; however, Fas is also constitutively
      expressed in many tissues, including liver. While the function of Fas in normal
      liver is unclear, many studies have demonstrated that Fas expression in liver is
      up-regulated under certain inflammatory conditions. A number of clinical reports
      also indicate that Fas expression and apoptosis are correlated with damage in
      liver during progression of several hepatic diseases. Therefore Fas may represent
      an attractive therapeutic target to control excessive or abnormal apoptosis in
      liver. One approach to regulate Fas expression in vivo is to use antisense
      oligonucleotides. This class of compound have been shown to be effective
      inhibitors of gene expression in many organs, including liver, and we have
      demonstrated protection of liver from apoptotic injury in animals by treatment
      with antisense oligonucleotides that inhibit Fas. In this article, we describe
      the evidence of a role for Fas in mediating some forms of liver disease and we
      review how antisense oligonucleotides can be used to prevent or control this
      pathology.

PMID- 12806431
TI  - Role of fractalkine in leukocyte adhesion and migration and in vascular injury.
AB  - Leukocyte adhesion and trafficking at the endothelium requires both cellular
      adhesion molecules and chemotactic factors. Fractalkine, a recently identified
      chemokine, has a unique architecture, a Cys-X-X-X-Cys chemokine domain presented
      on top of an extended mucin-like stalk as a part of transmembrane protein, and is
      expressed in a membrane-bound form on tumor necrosis factor-alpha and interleukin
      1-activated endothelial cells. Fractalkine receptor CX3CR1 is expressed on
      natural killer (NK) cells, monocytes and some portions of CD8(+) T cells.
      Interactions between fractalkine and CX3CR1 can mediate not only chemotaxis but
      also cell adhesion in the absence of substrates for other adhesion molecules.
      Furthermore, fractalkine activates NK cells, resulting in enhanced cytolysis of
      fractalkine expressing endothelial cells. Since endothelial cells are primary
      targets of immunologic attack, fractalkine seems to be involved in pathogenesis
      of vascular injury.

PMID- 12806432
TI  - Natural products of plant origin as anticancer agents.
AB  - Natural products have been used as effective remedies for the treatment of
      various ailments. Numerous plant products in the form of decoction, tincture,
      tablets and capsules have been clinically used for the treatment of different
      kinds of cancer. This review covers some of the important plants with clinically
      proven anticancer activity, including Catharanthus roseus, Podophyllum peltatum,
      Taxus brevifolia, Camptothecin acuminata, Cephalotaxus harringtonia, Viscum
      album, Onchrosia elliptica, Annona bullata, Asmina triloba and Rhizoma zedoariae.
      Synthetic analogues in some cases have also been prepared to improve the efficacy
      and decrease the side effects of parent compounds. The modes of action of
      clinically used drugs are also delineated.

PMID- 12806433
TI  - Molecule of the month. AN-1792.

PMID- 12806434
TI  - The discovery and synthesis of epinephrine.
AB  - Epinephrine (adrenaline) was the first hormone to be isolated. The events leading
      up to this were initiated by experiments conducted by an English physician on his
      son. The active compound of epinephrine was isolated as an iron complex and
      marketed in 1900 by Farbwerke Hoechst as Suprarenin. In 1901, Parke-Davis began
      to market Adrenalin, the manufacturing of which was challenged by rival
      companies. Further analysis of the product revealed a lack of purity, and further
      chemical structures were proposed. In 1906, Hoechst began production of synthetic
      epinephrine, the introduction of which made the hormone more cheaply available on
      the market. Although the hormone had initially been marketed as a vasoconstrictor
      to stop bleeding and to raise blood pressure in patients experiencing surgical
      shock, its main application had been the treatment of asthmatic attacks.
      Norepinephrine (noradrenaline) was discovered in 1907 to be not only a
      biosynthetic precursor of epinephrine, but also a neurotransmitter.

PMID- 12806435
TI  - Adaptations and innovations in drug delivery.
AB  - The most recent meeting organized by the Society for Medicines Research, entitled
      Improving Medicines Through Drug Delivery, was held at the National Heart and
      Lung Institute in London on July 5, 2001. Drug delivery is increasingly becoming
      a central technology in the research and development of better medicines. This is
      so for at least three reasons. First, new drugs are being derived from complex
      biological molecules that are not readily amenable to oral delivery. Second,
      improved medicine is recognized as requiring better dosing regimens for the
      patient. Both compliance and preference are improved by reduced dosing frequency,
      and it is rare for new products to require three-times-daily administration.
      Lastly, drug delivery technology has come a long way in the past 20 years, beyond
      controlled-release pharmaceuticals to polymer conjugates and dry powder-inhaled
      proteins.

PMID- 12806436
TI  - Frontiers in cardiovascular health.
AB  - The XVII World Congress of the International Society for Heart Research, held in
      Winnipeg, Canada, July 6-11, 2001, was attended by more than 3,000 delegates from
      55 countries. The gathering was a blend of clinical cardiologists, cardiothoracic
      surgeons and scientists working in experimental cardiology. The conference had an
      elaborate scientific program comprising 550 invited lectures divided into 82
      symposia. Besides the lectures, there were about 600 poster presentations. The
      well-planned scientific program covered the areas of investigative, molecular and
      experimental cardiology as well as recent advances in clinical cardiology and
      cardiothoracic surgery.

PMID- 12806437
TI  - State-of-the-art knowledge on thrombosis and hemostasis.
AB  - The XVIII Congress of the International Society on Thrombosis and Haemostasis,
      held July 6-12, 2001, in Paris, France, covered the latest advances in the field
      of thrombosis and hemostasis, including vascular biology. Plenary conferences,
      state-of-the-art lectures, symposia, and oral and poster presentations focused
      most of the attention on the current research on the pathogenesis and treatment
      of thrombotic and hemorrhagic disorders and provided updates on trials currently
      under way or already completed.

PMID- 12806438
TI  - Potential of modulatory cytokines in the rheumatoid arthritis process.
AB  - Rheumatoid arthritis is a chronic systemic disorder of unknown etiology. It is
      now generally accepted that the proinflammatory cytokines interleukin-1 (IL-1)
      and tumor necrosis factor-alpha are key mediators in the pathology of rheumatoid
      arthritis. Controlling the production and the activity of these mediators
      represents a major therapeutic goal. First data from clinical trials that showed
      efficacy, however, also revealed that blockade of these cytokines did not fully
      control the arthritis in all patients. Recent discoveries of novel cytokines in
      the pathology of arthritis such as IL-17, IL-18 and RANK ligand (RANKL) will help
      us better understand the pathogenesis of chronic arthritis and may contribute to
      improvement of current therapies. IL-4 and IL-10 are pleiotropic cytokines and
      are considered promising modulators in the control of rheumatoid arthritis.

PMID- 12806439
TI  - Role of histaminergic and cholinergic transmission in cognitive processes.
AB  - Mutual modulatory and functional interactions exist between the histaminergic and
      cholinergic systems in the brain. The activity of histaminergic neurons is
      permanently modulated by neighboring cholinergic neurons via muscarinic M(1)
      receptors, cholinergic transmission by histaminergic neurons through H(1), H(2),
      H(3A) and H(3B) receptors. In the nucleus accumbens, glutamatergic neurons
      originating from the hippocampus modulate cholinergic transmission in a direct
      way via stimulation of NMDA receptors located on cholinergic neurons.
      Additionally, glutamatergic neurons of the hippocampus modulate the activity of
      cholinergic neurons in an indirect way by stimulating histaminergic neurons
      within the nucleus accumbens. Reciprocal regulatory influences and
      neurotransmission are subjected to the global modulatory influence of nitric
      oxide. Both histaminergic and cholinergic systems in the nucleus accumbens are
      implicated in the response to aversive stimuli. Memory acquisition is associated
      with activation of cholinergic transmission in the nucleus accumbens, while
      stimulation of histaminergic neurons facilitates memory in a way that is
      independent of the cholinergic system. Hence, both histaminergic and cholinergic
      transmission within the nucleus accumbens and interactions between the two
      systems seem to play a predominant role in cognition.

PMID- 12806440
TI  - Molecule of the month. Miltefosine.

PMID- 12806441
TI  - Epinephrine analogues.
AB  - Tyramine was the first epinephrine analogue to be introduced into medicine, in
      the early 1900s. It was followed by ephedrine and pseudoephedrine in the 1920s
      and by the amfetamines a decade later. The popularity of the amfetamines grew
      throughout the 1930s and 1940s; after that, there was a slowly dawning
      realization that they were being widely abused. Isoprenaline, introduced in the
      1950s, was soon recognized as superior to epinephrine when used as an inhaler by
      asthmatics, and it remained the drug of choice for the relief of bronchospasm
      until around 1970. Orciprenaline, which featured an orcinol system, had a long
      duration of action and was active by mouth; Boehringer marketed it both as an
      inhaler and as a syrup for the prophylaxis of bronchospasm. The greatly superior
      bronchodilators salbutamol and terbutaline, launched in 1968 and 1970,
      respectively, incorporate further variation on the molecular theme that had led
      to the development of orciprenaline.

PMID- 12806442
TI  - Directions in urological research and drug therapies.
AB  - This meeting report summarizes advances and notable developments in the
      pharmaceutical management of urological diseases presented at various sessions
      during the Annual Meeting of the American Urological Association held in Anaheim,
      California, June 2-7, 2001. More than 10,000 attendees drawn from clinical and
      preclinical research deliberated on the latest trends in surgical and
      pharmacotherapeutic management in diverse areas of urology. In particular,
      several forums were dedicated to reviewing scientific trends, emerging concepts
      and therapies in urological diseases, such as overactive bladder, erectile
      dysfunction and lower urinary tract symptoms, which are the focus of this report.

PMID- 12806443
TI  - Successes and pitfalls of medical chemistry programs.
AB  - The RSC-SCI Medicinal Chemistry Symposium is a regular biennial event, always
      held at Churchill College, Cambridge, U.K. This year's meeting saw a diverse
      program of excellent medicinal chemistry presentations, mostly concentrated upon
      the early discovery and optimization stage, although discovery-enabling
      technologies were also discussed. The 24 lectures and 26 poster presentations
      provided details of a number of new clinical candidates, or first disclosures of
      the structures of clinical candidates, and of several new lead-generation
      programs.

PMID- 12806444
TI  - The role of sodium channels in disease.
AB  - Native sodium channels exist as polypeptide multimers of an alpha-subunit (260
      kDa) and subsidiary and smaller beta-subunits, which are divided into at least
      three subtypes--beta(1), beta(2) and beta(3). The alpha-subunits are structurally
      diverse, arising from multiple sodium channel genes and alternative splicing
      events. Recent progress has led to a good understanding of the molecular
      structure of sodium channels, how they work and the significance of their
      expression in particular cell types. This, coupled with experimental studies
      linking particular isoforms with particular disease states and the discovery of
      distinct human sodium channelopathies (specific mutations in specific isoforms
      that cause a variety of diseases, including paralysis, long QT syndrome and
      epilepsy), is beginning to reveal how particular sodium channel subtypes underlie
      specific pathologies. All this provides great potential for the development of
      new therapies. The first generation of sodium channel blockers has led to a broad
      spectrum anticonvulsant that is now widely used (lamotrigine) and an impressive
      neuroprotective agent that is in clinical trials for stroke (sipatrigine). The
      development of the next generation of sodium channel blockers will be greatly
      facilitated by elaboration of the pharmacology of the various isoforms, which
      itself is dependent upon the existence of reliable, rapid and high-throughput
      assays for sodium channel activity.

PMID- 12806445
TI  - Exercise in pregnancy.

PMID- 12806446
TI  - Uterine compression sutures as an alternative to hysterectomy for severe
      postpartum hemorrhage.

PMID- 12806448
TI  - Towards a more precise assay of sperm function in egg binding.
AB  - Historically, the treatment of severe male factor infertility has relied on donor
      sperm insemination. A decade ago the option of treating severe male factor
      infertility with partner sperm became a viable alternative. With the introduction
      of intracytoplasmic sperm injection (ICSI) in conjunction with in vitro
      fertilization (IVF), only men who produce no sperm are denied the option of
      fathering their own children. The use of ICSI has been extended to couples with
      mild male factors. Despite the known genetic risks (both inherent and de novo) of
      ICSI to offspring, couples with male factors as part of their infertility problem
      often prefer ICSI to standard IVF, due to apprehension that their sperm might not
      otherwise succeed in fertilization. This apprehension would be alleviated if an
      assay for the egg binding capability of human sperm were available. We examine
      here the possibility that recombinant human zona pellucida 3 (rec hZP3), the
      primary sperm receptor sulfoglycoprotein of the egg zona pellucida (ZP), be used
      as a human ZP surrogate for assessing sperm ability to bind to the ZP. Unlike
      human eggs, which cannot be obtained for this purpose, rec hZP3 can be produced
      in quantity. An efficient assay can be established by incubating sperm with rec
      hZP3 coated to a microwell plate. Infertile men with sperm having ability to bind
      to rec hZP3 can be advised to select standard IVF or intrauterine insemination,
      which have fewer genetic and medical risks.

PMID- 12806449
TI  - Clinical physiology of exercise in pregnancy: a literature review.
AB  - OBJECTIVES: To review the existing literature on the physiology of exercise in
      pregnancy as a basis for clinical practice guidelines for prenatal exercise
      prescription. METHODS: MEDLINE search for English language abstracts and articles
      published between 1966 and 2003 related to physiological adaptations to
      pregnancy, effects of pregnancy on responses to acute exercise and aerobic
      conditioning, effects of acute maternal exercise on indexes of fetal well-being,
      impact of physical conditioning on birth weight and other pregnancy outcomes, and
      use of exercise to prevent or treat gestational diabetes mellitus and
      preeclampsia. RESULTS: Maximal aerobic power (VO(2)max, L/min) is well-preserved
      in pregnant women who remain physically active, but anaerobic working capacity
      may be reduced in late gestation. The increase in resting heart rate, reduction
      in maximal heart rate, and resulting smaller heart rate reserve render heart rate
      a less precise way of estimating exercise intensity. As rating of perceived
      exertion (RPE) is not altered by pregnancy, the use of revised pulse rate target
      zones along with Borg's RPE scale is recommended to prescribe exercise intensity
      during pregnancy. Responses to prolonged submaximal exercise (>30 min) in late
      gestation include a moderate reduction in maternal blood glucose concentration,
      which may transiently reduce fetal glucose availability. The normal response to
      sustained submaximal exercise is an increase in fetal heart rate (FHR) baseline.
      Transient reductions in FHR reactivity, fetal breathing movements, and FHR
      variability may also occur in association with more strenuous exercise.
      Controlled prospective studies have demonstrated that moderate prenatal exercise
      during the second and third trimesters is useful to improve aerobic fitness and
      maternal-fetal physiological reserve without affecting fetal growth. CONCLUSIONS:
      The Physical Activity Readiness Medical Examination for Pregnancy is recommended
      for use by physicians and midwives to provide medical clearance for prenatal
      exercise. Evidence-based prenatal exercise guidelines are needed to counsel
      healthy and fit pregnant women on the safety of involvement in more strenuous
      physical conditioning. Future study is also recommended to determine the
      usefulness of prenatal exercise in the prevention and treatment of gestational
      diabetes mellitus and preeclampsia.

PMID- 12806450
TI  - Pelvic floor exercises during and after pregnancy: a systematic review of their
      role in preventing pelvic floor dysfunction.
AB  - OBJECTIVE: To review the literature on the origin, anatomical rationale,
      techniques, and evidence-based effectiveness of peripartum pelvic floor exercises
      (PFEs) in the prevention of pelvic floor problems including urinary and anal
      incontinence, and prolapse. DATA SOURCES: Literature was reviewed for background
      information. MEDLINE, EMBASE, CINAHL, and proceedings of scientific meetings were
      searched for evidence-based data. A comprehensive literature search was performed
      to find all studies that involved the use of antepartum and/or postpartum PFEs.
      For the MEDLINE (1966 to 2002) and CINAHL (1980 to 2002) searches, the following
      key words were used: urinary incontinence (prevention and control,
      rehabilitation, therapy), fecal incontinence, exercise or exercise therapy,
      Kegel, muscle contraction, muscle tonus, muscle development, pelvic floor,
      pregnancy, puerperium, puerperal disorders. For the EMBASE (1980 to 2002) search,
      the following key words were used: micturition disorder (prevention, rehab,
      disease management, therapy), fecal incontinence, labour complication, pregnancy
      disorder, puerperal disorder, antepartum care, pregnancy, kinesiotherapy,
      exercise, pelvic floor, bladder. A manual search was performed of available
      abstracts presented at the annual scientific meetings of the International
      Continence Society (1997, 1999 to 2002), American Urogynecologic Association
      (1997 to 1998, 2000 to 2002), and International Urogynecological Association
      (1997, 1999 to 2002). Twelve studies evaluating the role of antepartum PFE were
      found, of which 3 randomized controlled trials (RCTs) comparing PFEs for the
      prevention of urinary incontinence to controls were included. Twelve studies
      evaluating postpartum PFEs for prevention of urinary incontinence were reviewed,
      of which 4 RCTs were included. Five studies evaluating postpartum PFEs for the
      prevention of anal incontinence were reviewed, of which 4 RCTs were included.
      Participants in the studies were primiparous women. DATA TABULATION AND
      INTEGRATION: Data were extracted using a standardized collection form. Quality of
      the data was evaluated using the Jadad scale. Where possible, a meta-analysis was
      conducted using a random effect model. Heterogeneity between trials was assessed
      and sensitivity analyses were performed. RESULTS: Antepartum PFEs, when used with
      biofeedback and taught by trained health care personnel, using a conservative
      model, does not result in significant short-term (3 months) decrease in
      postpartum urinary incontinence, or pelvic floor strength. Postpartum PFEs, when
      performed with a vaginal device providing resistance or feedback, appear to
      decrease postpartum urinary incontinence and to increase strength. Reminder and
      motivational systems to perform "Kegel" exercises are ineffective in preventing
      postpartum urinary incontinence. Postpartum PFEs do not consistently reduce the
      incidence of anal incontinence. CONCLUSION: Postpartum PFEs appear to be
      effective in decreasing postpartum urinary incontinence. Data regarding the
      effect of PFEs on prevention of anal incontinence are lacking, and also on its
      prevention of prolapse.

PMID- 12806451
TI  - Emergency contraception: models to increase accessibility.
AB  - Much of the recent focus on emergency contraception (EC) has been on the need to
      increase the availability of EC without a prescription. Barriers to the wider
      accessibility of EC include the need to use the medication within a 72-hour
      window, cost, and knowledge about its availability. Concerns about the non
      prescription accessibility of EC include missing the opportunity to see a
      physician, possible reduced use of barrier contraceptives and the resulting
      increase in sexually transmitted infections, and overuse of EC and underuse of
      regular contraception. As the wider availability of EC is a reality, and pressure
      to further increase its access is growing, it is timely that issues surrounding
      accessibility of EC be discussed. This paper explores the issues around making EC
      more accessible and the various models of obtaining EC, namely, prescription
      medication, pharmacist-physician collaboration, pharmacist-dispensed medication,
      schedule II (behind the counter) medication, or on-the-shelf medication. The
      ideal model will be the one that provides improved accessibility for adolescents,
      other low-income women, and indeed for all women. Increased accessibility of EC
      should also lead to cost savings for the health-care system because of fewer
      unwanted pregnancies.

PMID- 12806452
TI  - Investigating adverse outcomes in obstetrics.
AB  - Investigation of adverse outcomes in health care requires a systematic and
      systemically oriented approach. This is true in obstetrics where, in Western
      countries such as Canada, adverse outcomes in the form of maternal mortality are
      rare. A model for such investigation is presented, based on answers to 3
      questions: What? How? and Why? These questions correspond to Donabedian's 3
      components of quality assurance: Outcome, Process, and Structure, respectively.
      Aspects of Reason's model of accidents are also included, in the form of "active
      failures" and "latent conditions." The latter are divided into 5 basic
      contributory factors, 4 of which are derived from Helmreich's model of human
      factors influencing behaviour in flight-crew environments. To illustrate its
      basic nature, the model is applied to a previously well-investigated air crash at
      Dryden, Ontario, and 3 obstetric cases of maternal mortality. Application of the
      model to the reactive investigation of close calls is discussed, as is
      application to the proactive interrogation of the system for the presence and
      nature of hazards that pose threats to safety.

PMID- 12806453
TI  - Exercise in pregnancy and the postpartum period.
AB  - OBJECTIVE: To design Canadian guidelines advising obstetric care providers of the
      maternal, fetal, and neonatal implications of aerobic and strength-conditioning
      exercises in pregnancy. OUTCOMES: Knowledge of the impact of exercise on
      maternal, fetal, and neonatal morbidity, and of the maternal measures of fitness.
      EVIDENCE: MEDLINE search from 1966 to 2002 for English-language articles related
      to studies of maternal aerobic and strength conditioning in a previously
      sedentary population, maternal aerobic and strength conditioning in a previously
      active population, impact of aerobic and strength conditioning on early and late
      pregnancy outcomes, and impact of aerobic and strength conditioning on neonatal
      outcomes, as well as for review articles and meta-analyses related to exercise in
      pregnancy. VALUES: The evidence collected was reviewed by the Society of
      Obstetricians and Gynaecologists of Canada (SOGC Clinical Practice Obstetrics
      Committee) with representation from the Canadian Society for Exercise Physiology,
      and quantified using the evaluation of evidence guidelines developed by the
      Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. All women
      without contraindications should be encouraged to participate in aerobic and
      strength-conditioning exercises as part of a healthy lifestyle during their
      pregnancy. (II-1,2B) 2. Reasonable goals of aerobic conditioning in pregnancy
      should be to maintain a good fitness level throughout pregnancy without trying to
      reach peak fitness or train for an athletic competition. (II-1,2C) 3. Women
      should choose activities that will minimize the risk of loss of balance and fetal
      trauma. (III-C) 4. Women should be advised that adverse pregnancy or neonatal
      outcomes are not increased for exercising women. (II-1,2B) 5. Initiation of
      pelvic floor exercises in the immediate postpartum period may reduce the risk of
      future urinary incontinence. (II-1C) 6. Women should be advised that moderate
      exercise during lactation does not affect the quantity or composition of breast
      milk or impact infant growth. (I-A) VALIDATION: This guideline has been approved
      by the SOGC Clinical Practice Obstetrics Committee, the Executive and Council of
      SOGC, and the Board of Directors of the Canadian Society for Exercise Physiology.
      SPONSORS: This guideline has been jointly sponsored by the Society of
      Obstetricians and Gynaecologists of Canada and the Canadian Society for Exercise
      Physiology.

PMID- 12806454
TI  - Identification and purification of immunogenic proteins from nonliving
      promastigote polyvalent Leishmania vaccine (Leishvacin ).
AB  - Immunogenic proteins from nonliving promastigote polyvalent Leishmania vaccine
      against American tegumentary leishmaniasis (Leishvacin ), produced by Biobr s
      (Biochemistry of Brazil ), Montes Claros, State of Minas Gerais, Brazil, were
      identified and purified by polyacrylamide electrophoresis gel and electroelution.
      C57BL/10 mice were vaccinated with proteins with estimated molecular weights of
      42, 46, 63, 66, 73, 87, 97, and 160kDa in three doses of 30 g of each protein at
      15-day intervals combined with 250 microg of Corynebacterium parvum followed by a
      challenge infection with 10(5) infective promastigotes from Leishmania
      (Leishmania) amazonensis. The ability of these proteins to induce immune response
      and protection was analyzed. No statistical difference was observed in the level
      of IFN-gamma induced by proteins in vaccinated groups in comparison with control
      groups. Six months after challenge infection, protection levels of 28.57; 42.86;
      57.14; 42.86; 42.86, 57.14; 42.86 and 57.14% were demonstrated for each purified
      protein.

PMID- 12806455
TI  - Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones
      isolated from the highly resistant Colombian strain.
AB  - The present investigation was performed to evaluate the susceptibility of seven
      clones isolated from the highly resistant Colombian strains, prototype of Biodeme
      Type III. Seven clones previously obtained, showed a phenotypic homogeneity and
      high similarity with the parental strain. Eight groups of 30 mice were inoculated
      with one of seven clones or the parental strain; 20 were treated with
      benznidazole (100mg/kg/day) and 10 were untreated controls. Cure evaluations were
      done by parasitological and serological tests and PCR. Cure rates varied from 0%
      (null) to 16.7%. Correlation between positivity of parasitological and
      serological tests with positive PCR reached 37%. The results demonstrated the
      high resistance of the clones, suggesting the predominance of a highly resistant
      principal clone in this strain. The findings apparently indicate that the
      possibility of cure is minimal for patients infected with this biodeme; a fact
      that could affect the control of Chagas' disease through treatment of chronically
      infected people.

PMID- 12806456
TI  - [Schistosomiasis in hyperendemic area of Taquarendi: I- Schistosoma mansoni
      infection and severe clinical forms].
AB  - The study was carried out in Taquarendi (Bahia), a caatinga zone with a small
      irrigated strip of land, where Biomphalaria glabrata snails are found. From the
      1,532 inhabitants, 1,105 (72.1%) were submitted to clinical examination and 1058
      out of them (95.7%) made stool examinations. Prevalence of schistosomiasis was
      73.1% and 16.2% of these patients eliminated more than 1,000 eggs per gram of
      stool. By clinical examination, the size and the consistency of the left liver
      lobe were increased in 54% of the individuals and the spleen was palpable in
      21.8%. The diagnosis of hepatosplenomegaly and of the advanced hepatointestinal
      clinical form was made, respectively, in 9.8% and 3.7%. A direct relationship
      between such clinical forms of the disease and the worm load over 1.000 S.
      mansoni eggs/g of fezes was found.

PMID- 12806457
TI  - [Involvement of the renal function in patients with visceral leishmaniasis (kala
      azar)].
AB  - Evaluation of the renal involvement of visceral leishmaniasis (kala-azar) aiming
      at verifying clinical and laboratorial repercussions of the renal implication on
      VL. Laboratory analysis was performed of blood and urine samples collected
      immediately after confirming diagnosis through the finding of Leishmania in bone
      marrow. Two (18.1%) patient presented complications associated with kala-azar.
      Five patients (45.4%) presented macroscopic hematuria and one case (N  9)
      clinical manifestations compatible with an acute nephritis syndrome. Laboratorial
      data of urine exam showed: proteinuria in 10 (90.9%) patients, hematuria in 7
      (63.6%) and leukocyturia in 6 (54.5%) cases. Nine (81.8%) patients presented high
      levels of microalbuminuria, characterizing glomerular lesion. The presence of
      proximal tubulopathy, measured through retinol binding protein observed in 5
      (45.4%) cases. CONCLUSION: renal involvement was manifested in most subjects,
      contributing to the severity of the disease.

PMID- 12806458
TI  - [Treatment of children with malaria Plasmodium falciparum with derivatives
      artemisinin].
AB  - From January 1996 to December 1998, artemisinin derivatives were prescribed to
      108 children infected with Plasmodium falciparum. The therapeutic effect was
      evaluated. Only children with moderate or severe malaria were included. Group I
      (intravenous artesunate; n = 62): 50.8% with moderate malaria and 49.2% with
      severe malaria; 53.2% with mild parasitemia, 22.6% with moderate parasitemia and
      24.2% with high parasitemia; Group II (intramuscular artemether [Paluter ]; n =
      46): 67.4% with moderate malaria and 32.6% with severe malaria; 52.2% with mild
      parasitemia, 36.2% with moderate parasitemia and 15.2% with high parasitemia;
      clinical amelioration and clearance of parasitemia showed no statistical
      difference between the groups. All patients cleared the parasitemia at the
      seventh day of follow-up (D7). In order to avoid recrudescence, mefloquine or
      clindamycin was used.

PMID- 12806459
TI  - [Leptospiral infection and subclinical presentation among children in Salvador,
      Bahia].
AB  - The purposes of this investigation were to identify the frequency and risk
      factors of leptospiral infection among children aged between 2 and 15 years in
      Salvador, Bahia, household contacts of patients (index-cases) hospitalized at
      Couto Maia Hospital due to Leptospira interrogans (ELISA IgM positive). Among 148
      household contacts from 25 selected index-cases, clinical and epidemiological
      data were collected and ELISA IGM and IgG were performed in paired sera (between
      20 days) from 73 (49.3%). This diagnostic method divided the 73 household
      contacts into three groups: group A (acute or recent leptospiral infection), 30
      (41.1%) children, group B (not- infected ) 34 (46.6%) and group C, (past
      infection) nine (12.3%) children. In group A five (16.7%) had cold syndrome
      simile. No statistically significant difference was found between groups A and B
      for sex, race, age and presence of pet dog. However, in group A there was a
      statistically significant predominance (p < 0.05%) of: contact with natural water
      courses; index-case sibling aged under fifteen years; female sex and over 9 years
      old; and principally lack of appropiate trash disposal in the residential area.
      In conclusion, leptospiral infection in children (from 2 to 15 years of age) in
      Salvador is underestimated, because it is asymptomatic or presents as a cold
      syndrome simile.

PMID- 12806460
TI  - [Short course schemes for vivax malaria treatment].
AB  - with the objective of evaluating shortened therapeutic outlines effective in
      vivax malaria treatment, we accomplished an open, prospective study allocating
      234 patients with vivax malaria distributed at random into eight therapeutic
      groups. Six groups used oral arthemisin as blood esquizonticide at different
      doses for one day and the other two groups received chloroquine in a single dose.
      The primaquine was used as a hypnozoiticide in all groups. They received a daily
      dose of 30mg in the course of five or seven days in all groups. The clearance of
      parasitaemia in patients treated with arthemisin (independent of dosage) was
      faster than the chloroquine group (p <0.01). Cure was acheived in 92.3% and
      80.2%, in patients treated with primaquine for seven or five days, respectively
      (p=0.0372).

PMID- 12806461
TI  - Trypanosoma cruzi in marsupial didelphids (Philander frenata and Didelhis
      marsupialis): differences in the humoral immune response in natural and
      experimental infections.
AB  - Philander frenata and Didelphis marsupialis harbor parasitism by Trypanosoma
      cruzi without developing any apparent disease and on the contrary to D.
      marsupialis, P. frenata maintains parasitism by T. cruzi II subpopulations. Here
      we compared the humoral immune response of the two didelphids naturally and
      experimentally infected with T. cruzi II group, employing SDS-PAGE/Western blot
      techniques and by an Indirect immunofluorescence assay. We also studied the
      histopathological pattern of naturally and experimentally infected P. frenata
      with T. cruzi. P. frenata sera recognized more antigens than D. marsupialis, and
      the recognition pattern did not show any change over the course of the follow up
      of both didelphid species. Polypeptides of 66 and 90kDa were the most prominent
      antigens recognized by both species in the soluble and enriched membrane
      fractions. P. frenata recognized intensely also a 45kDa antigen. Our findings
      indicate that: 1) there were no quantitative or qualitative differences in the
      patent or subpatent phases in the recognition pattern of P. frenata; 2) the
      significant differences in the recognition pattern of parasitic antigens by P.
      frenata and D. marsupialis sera suggest that they probably "learned" to live in
      harmony with T. cruzi by different strategies; 3) although P. frenata do not
      display apparent disease, tissular lesions tended to be more severe than has been
      described in D. marsupialis; and 4) Both didelphids probably acquired infection
      by T. cruzi after their evolutionary divergence.

PMID- 12806462
TI  - [Montenegro intradermoreaction after the test sequential repetitions in
      Porteirinha, Minas Gerais State, Brazil].
AB  - With the purpose of evaluating the response of sequential applications of
      Montenegro intradermoreaction (IDRM), we have repeated four times the test in the
      inhabitants of an endemic area for kala-azar, that resulted negative 3-4 years
      ago. Firstly, we have repeated three IDRM in those who remained negative, with a
      60-day interval among them. In the second stage, we have performed a last
      reaction in all participants of the study. From the total of 49 individuals with
      prior negative IDRM, 19 (38.8%) have positivated the test in some of the times,
      17 (34.7%) have given up the study and 13 (26.5%) remained with a negative result
      in all the applications. In the second stage, the repetition of IDRM has shown
      that from the 14 positive in some of the tests, 8 remained like this and 6 have
      become negative. Our results confirm the possibility of late hypersensitivity
      induction in some individuals as a consequence of IDRM application.

PMID- 12806463
TI  - [Surgical treatment of portal hypertension in schistosomiasis mansoni].
AB  - Portal hypertension is defined by an hepatic venous pressure gradient greater
      than 5mmHg. It is usually caused by an increase in resistance in the portal
      hepatic vascular bed due to obstruction to flow. The severe forms of
      schistosomiasis usually evolve with portal hypertension, esophageal,
      intraabdominal, retroperitoneal and abdominal wall varices. Massive bleeding due
      to esophageal or gastric variceal rupture is the major complication of portal
      hypertension in schistosomiasis. In regard to treatment, clinical (propranolol,
      somatostain, octreotide), endoscopic (sclerotherapy, clips and ligature of
      varices), vascular (TIPS - transjugular intrahepatic portosystemic shunt) and
      surgical (portosystemic shunts and portovariceal disconnection) approaches have
      been tried to decrease portal hypertension and prevent bleeding. In the present
      review the author discusses the subject emphasizing the surgical procedures.

PMID- 12806464
TI  - [Influenza].
AB  - Influenza (flu) is an acute contagious viral infection characterized by
      inflammation of the respiratory tract that every winter affects more than 100
      million people in Europe, Japan and the United States of America, also being
      responsible for several thousand of excess deaths (data from the United States
      reveal between 20,000 to 40,000 excess deaths annually). The Mixovirus influenzae
      is the agent that causes influenza, commonly called flu. There are 3 types of
      influenza virus: A, B, C, and only types A and B are perceived to be clinically
      relevant in humans. Due to the segmented nature of its genetic material, the
      influenza virus is highly mutagenic, causing frequent insertion of new antigenic
      strains into the community, against which the population presents no immunity.
      Presently, there are few options for the control of influenza and annual
      immunization is the most effective means to prevent disease and its
      complications. In Brazil, according to data collected by the VigiGripe's Project 
      linked to the Federal University of Sao Paulo -, circulation of the influenza
      virus also has a seasonal pattern, with peak activity occurring between May and
      September. Yearly vaccination is, therefore, best indicated on March and April.
      Currently, there are four medications available for the treatment of influenza
      viruses: amantadine and rimantadine, and two second generation pharmaceutical
      products, the neuraminidase inhibitors, oseltamivir and zanamivir. The latter two
      drugs have set the stage for a new approach to the management and control of
      influenza infections.

PMID- 12806465
TI  - [Yellow Fever].
AB  - Yellow fever is an infectious and non-contagious disease caused by an arbovirus,
      the yellow fever virus. The agent is maintained in jungle cycles among primates
      as vertebrate hosts and mosquitoes, especially Aedes in Africa, and Haemagogus
      and Sabethes in America. Approximately 90% of the infections are mild or
      asymptomatic, while 10% course to a severe clinical picture with 50% case
      fatality rate. Yellow fever is largely distributed in Africa where urban
      epidemics are still reported. In South America, between 1970-2001, 4,543 cases
      were reported, mostly from Peru (51.5%), Bolivia (20.1%) and Brazil (18.7%). The
      disease is diagnosed by serology (detection of IgM), virus isolation,
      immunohistochemistry and RT-PCR. Yellow fever is a zoonosis and cannot be
      eradicated, but it is preventable in man by using the 17D vaccine. A single dose
      is enough to protect an individual for at least 10 years, after which
      revaccination is recommended. In this paper, the main concepts about yellow fever
      as well as the fatal adverse effects of the vaccine are updated.

PMID- 12806466
TI  - [Fatal case during treatment of american tegumentary leishmaniasis with sodium
      stibogluconate bp 88  (shandong xinhua)].
AB  - The authors report the occurrence of a fatal case in patient with cutaneous
      leishmaniasis in the municipality of Caxias, MA. Male patient, 22 years old, road
      sweeper, presented with an ulcer in left leg, diagnosed as cutaneous
      leishmaniasis and treated with sodium stibogluconate BP88 (Sb+5) (Shandong
      Xinhua) at a dose of 10mg/Sb+5/kg/day/20 days. After dose three he presented
      arthralgia, myalgia, nausea and weakness. During the therapy there was an
      aggravation of the symptoms with abdominal pain and irradiation into the thorax.
      After dose seven he presented a picture of associated dyspnea and thoracic pain
      of mild intensity. At dose nine there was further worsening of the picture,
      nevertheless the therapy was continued up to dose 11, when the patient's state
      deteriorated to such an extent that he was hospitalized in the intensive care
      unit. Exams: erythrocytes, 4.4 million; hemoglobin, 10.6%; hematocrits, 35%;
      white blood cells 26,400, basophiles and myelocytes (0); segmented leukocytes,
      59%; lymphocytes 30%; monocytes 2%; platelets (normal); glucose, 42mg%; urea,
      73mg%; creatinine, 2.4mg%; and ECG (blockade of right branch). The patient died
      from cardiorespiratory insufficiency. The current report underscores the need to
      clarify health workers regarding the use of Sb+5 and also to remind the Health
      Ministry to verify the quality and origin when acquiring new products.

PMID- 12806467
TI  - Clinical presentation of parvovirus B19 infection in HIV-infected patients with
      and without AIDS.
AB  - Human parvovirus B19 replicates in erythrocyte precursors. Usually, there are no
      apparent hematological manifestations. However, in individuals with high
      erythrocyte turnover, as in patients with sickle-cell disease and in the fetus,
      the infection may lead to severe transient aplasia and hydrops fetalis,
      respectively. In AIDS patients, persistent infection may result in chronic
      anemia. By contrast, in HIV-positive patients without AIDS the infection evolves
      as a mild exanthematous disease. Two clinical descriptions exemplify these forms
      of presentation. In the first, an AIDS patient presented with bone marrow failure
      that responded to immunoglobulin. In the second, an HIV-positive patient without
      AIDS had a morbilliform rash, and needed no treatment. Knowing that an AIDS
      patient has chronic B19 anemia lessens concern about drug anemia; protects the
      patient from invasive diagnostic maneuvers; and prevents the patient from
      disseminating the infection. In AIDS patients with pure red cell aplasia, a
      search for parvovirus B19 DNA in the serum or in the bone marrow is warranted.

PMID- 12806468
TI  - [Preservation of Cryptosporidium oocystis in fecal specimens for parasitological
      examination].
AB  - By using a simple and easily available device which contains a 10% buffered
      formaldehyde solution, fecal samples are rendered odorless and can be stored at
      room temperature with no biosafety hazards. Cryptosporidium oocysts contained in
      such fecal samples can be identified without difficulty by using the Kinyoun
      method. This system permits an adequate preservation of the material, which
      facilitates the execution of tasks related to assistance and epidemiology.

PMID- 12806469
TI  - [Pretentious and deified papers].

PMID- 12806470
TI  - Mucosal leishmaniasis.

PMID- 12806471
TI  - Aging and public health.

PMID- 12806473
TI  - [The quest for adequate health care for the elderly: literature review and the
      application of an instrument for early detection and prediction of diseases].
AB  - The increase in the elderly population demands changes in health care models by
      policymakers to deal with the substantial cost increase This article addresses
      patient access flow and the definition of priorities in an outpatient unit. A
      short questionnaire (8 questions) was used to assess enrollment and ranking of
      the elderly at risk of repeated hospital admissions, considered as a proxy for
      frailty. In a sample of 360 individuals, 75.8% of the elderly population was
      classified as "low risk". However, approximately 11% of the sample was considered
      to be at "medium" or "high" risk of becoming ill and requiring intensive use of
      health services. Our findings corroborate the usefulness (for promoting an
      effective health system for the elderly) of the proposed questionnaire as a tool
      to classify the elderly in different "frailty groups", using a hierarchic
      definition of vulnerability. The proposed ranking procedure can help adjust the
      portal of entry into the system, as used thus far in most Brazilian health
      facilities. The article concludes by suggesting that the validity of the method
      be tested in a prospective study.

PMID- 12806474
TI  - [Prevalence, associated factors, and misuse of medication in the elderly: a
      review].
AB  - Most elderly people use at least one medication, and about one-third use more
      than five drugs simultaneously. Many patients have no access to the drugs they
      most need, and others use unnecessary or dangerous drugs. The mean number of
      drugs used by the elderly, as quoted in different studies, varies from 2 to 5.
      Significant predictors for such misuse of medication are older age, female
      gender, precarious health conditions, and depression. Cardiovascular drugs, anti
      rheumatics, and analgesics are the most frequently consumed therapeutic classes.
      Multiple use, prescription of contraindicated drugs, redundant use, and
      inadequate training of the health care team are associated with adverse drug
      effects and interactions. Better quality of prescriptions and research on drug
      use can bring benefits to people aged 60 years or older.

PMID- 12806475
TI  - [The aging process in the Brazilian population: a demographic approach].
AB  - Contrary to common sense, the population aging process is due to the decline in
      fertility rather than mortality. The aging process began around the end of the
      19th century in a number of Western European countries, expanded to the rest of
      the so-called First World over the past century, and reached several Third World
      countries afterwards, including Brazil over the last decades. In the Brazilian
      case, a sharp and widespread fertility decline began by the end of the 1960s, and
      an accelerated population aging process can thus be expected. This process will
      necessarily be faster and with deeper structural changes, demographically
      speaking, than in First World countries, for two reasons: the fertility decline
      in Brazil was faster, and it took place in a population with a younger age
      structure.

PMID- 12806476
TI  - [Aging with dependence: family needs and responsibilities].
AB  - This article highlights the phenomenon of "aging with dependence" as a challenge
      to be dealt with by the field of collective health and discusses responsibilities
      for providing health care to this population contingent, comparing the necessary
      and existing conditions for families to assume responsibility for such care. The
      analysis is based on authors and theoretical references involving studies on
      aging, dependence, public policies, and available community resources for health
      care for the elderly. The following themes are emphasized: dependence and aging,
      the economic issue of dependence, family care, and family needs. The article
      concludes that since dependence is a dynamic process, it should be approached
      through programs that range from health promotion strategies to the establishment
      of support networks for long-term care in the community. These programs should be
      part of a public policy that involves all sectors of society and that can provide
      back-up for dependent seniors, with or without family support.

PMID- 12806477
TI  - [Health status, physical functioning, health services utilization, and
      expenditures on medicines among Brazilian elderly: a descriptive study using data
      from the National Household Survey].
AB  - The objective of this research was to describe health conditions and health
      services utilization among Brazilian seniors. The study was based on 28,943
      adults > 60 years (99.9%) from an overall National Household Survey (PNAD 1998).
      The results show that prevalence rates for at least one chronic disease (69.0%),
      hypertension (43.9%), arthritis (37.5%), and inability to feed oneself/bathe/use
      the toilet (2.0%) are very similar to those observed in other populations.
      Physician visits and hospitalization patterns are within the variation reported
      by different countries. The low prevalence rates of older adults who had
      interrupted activities because of a health problem (13.9%) or had been bedridden
      (9.5%) in the previous 2 weeks or hospitalized in the previous year (13.6%) show
      that the vast majority are not subject to these events. Considering that 50% of
      this population live on less than or equal to one Brazilian monthly minimum wage,
      expenditures on medications consume approximately one-fourth (23%) of total
      income for half of the elderly population.

PMID- 12806478
TI  - [Socioeconomic circumstances and health among the brazilian elderly: a study
      using data from a National Household Survey].
AB  - The influence of socioeconomic circumstances on senior citizens' health is still
      controversial. We used data from the 1998 Brazilian National Household Survey
      (PNAD 1998) to examine this influence. A representative sample of the Brazilian
      population aged > or = 65 years (n = 19,068) were included in the study. The
      characteristics of those in the lower quintile of per capita household income
      were compared with those with higher income (< 0.67 vs > or = 0.67 the Brazilian
      minimum wage). The lower income group presented worse health conditions (self
      rated health, inability to perform routine activities due to a health problem,
      bedridden conditions, and a report of any disease), and worse physical
      functioning (level of difficulty in performing selected physical activities), and
      less frequent use of medical and dental services. These results do not confirm
      observations, in some developed countries, of a lack of association between
      socioeconomic status and health among the elderly. On the contrary, according to
      our results, in Brazil even small differences in income are sufficiently
      sensitive to identify older adults with worse health conditions and limited
      access to health services.

PMID- 12806479
TI  - [Health, work, and aging in Brazil].
AB  - The rapid aging process of the Brazilian population is accompanied by a similar
      change in the composition of the country's work force. The objective of this
      study is to determine health differentials in the elderly according to their
      insertion in the work market, after considering the influence of socio
      demographic factors. This study included 2,886 males > or = 65 years residing in
      ten Brazilian metropolitan areas and included in the National Household Survey
      conducted by the National Institute of Geography and Statistics, or National
      Census Bureau (IBGE) in 1998. The analysis included the chi-square and odds
      ratios estimated by multiple logistic regression. More than a fourth of the
      elderly worked. Among the formally retired elderly, those who still worked were
      younger seniors, those with more schooling, and those with higher per capita
      family income; they reported fewer chronic diseases and presented less difficulty
      in performing their activities of daily living, but did not show any differences
      in relation to health services utilization. According to our results, health and
      especially indicators of autonomy and physical mobility are independent
      predictive factors for the elderly to remain active.

PMID- 12806480
TI  - [Violence against the elderly: the relevance of an old health problem].
AB  - This article presents data on morbidity and mortality due to "external causes"
      among the Brazilian elderly and a review of the Brazilian and international
      literature on the theme. The data refer to the period from 1980 to 1998. The main
      sources were the Mortality Information System (SIM) and the Hospital Information
      System of the Unified National Health System (SIH-SUS). The basic cause of death
      was evaluated according to the 9th Review of the International Classification of
      Diseases (ICD9) for 1980 to 1995 and based on the 10th Review since then. The
      Brazilian and international literature review was based on texts from MEDLINE,
      LILACS, and Informa. Accidents and violence are the 6th most common cause of
      death among individuals 60 years of age and older in Brazil. The majority of
      hospitalizations from external causes involve lesions from falls and injuries to
      older pedestrians by motor vehicles. However, violence against elderly Brazilians
      is more widespread and varied than this, as reflected by cases of physical,
      psychological, sexual, and financial abuse and neglect that fail to reach the
      health care system; rather, such cases are "taken for granted", seen as basically
      natural within the daily routine of family relations and various forms of social
      and public policy neglect.

PMID- 12806481
TI  - [Determinant factors for healthy aging among senior citizens in a large city: the
      Epidoso Project in Sao Paulo].
AB  - Population aging leads to an increase in the prevalence of chronic and disabling
      diseases, as well as a change in the public health paradigm. Diseases diagnosed
      in the elderly are generally not curable; if not properly treated and monitored
      over time, they tend to generate complications and sequelae that impair patients'
      independence and autonomy. Health is no longer measured by the presence or
      absence of disease, but by the degree of preservation of functional capacity.
      Factors for healthy aging with good functional capacity and those which increase
      the risk of death and disability need to be identified by longitudinal surveys
      that include the elderly population living in the community. This article
      presents data from the first follow-up survey of senior citizens in Brasil,
      called the Epidoso Project (from "epi" as in "epidemiologic" and "idoso" or
      "elderly" in Portuguese) implemented since 1991 in the city of Sao Paulo. The
      socio-demographic, clinical, and functional characteristics of a cohort of
      elderly are discussed, with a risk analysis for death and disability, and the
      implications for health planning are considered.

PMID- 12806482
TI  - [Cardiovascular mortality predictors in the oldest old].
AB  - This article investigates the association between cardiovascular risk factors and
      cardiovascular morbidity and mortality in the oldest old. In 1996, 91% of the
      population > or = 80 years of age from Veranopolis, Rio Grande do Sul State,
      Brazil, were evaluated to detect cardiovascular risk factors and morbidity. The
      sample was followed up for three years, with the assessment of deaths. The
      analysis was done using univariate statistics and multivariate logistic
      regression analysis. There were 41 deaths (21%): 20 men and 21 women. Deaths were
      distributed by year as follow: 03 (7.3%) in the first year, 08 (19.5%) in the
      second, and 30 (73.2%) in the third. There was a significant and independent
      association between death and the following variables: diastolic blood pressure
      (DBP), total cholesterol (TC), LDL-C, ApoA-I, prior stroke (CVA), right bundle
      branch block (RBBB), and left ventricular hypertrophy (LVH) by ECG. Survivors
      presented higher levels of DBP, TC, LDL-C, ApoA-I, CVA, RBBB and LVH. According
      to the multivariate analysis, the variables were independent risk factors for
      mortality. Cardiovascular risk factors appear to have a distinct impact on the
      oldest old.

PMID- 12806483
TI  - The relationship between dental status, food selection, nutrient intake,
      nutritional status, and body mass index in older people.
AB  - This paper reviewed the findings from a national survey in Great Britain which
      assessed whether dental status affected older people's food selection, nutrient
      intake, and nutritional status. The survey analyzed national random samples of
      free-living and institution subjects for dental examination, interview, and four
      day food diary as well as blood and urine tests In the free-living sample,
      intakes of non-starch polysaccharides, protein, calcium, non-heme iron, niacin,
      and vitamin C were significantly lower in edentulous as compared to dentate
      subjects. People with 21 or more teeth consumed more of most nutrients,
      particularly non-starch polysaccharides. This relationship in intake was not
      apparent in the hematological analysis. Plasma ascorbate and retinol were the
      only analytes significantly associated with dental status. Having 21 or more
      teeth increased the likelihood of having an acceptable body mass index (BMI).
      Thus, maintaining a natural and functional dentition defined as having more than
      twenty teeth into old age plays an important role in having a healthy diet rich
      in fruits and vegetables, a satisfactory nutritional status, and an acceptable
      BMI.

PMID- 12806484
TI  - The Bambui Health and Aging Study (BHAS): factors associated with the treatment
      of hypertension in older adults in the community.
AB  - The objective of this study was to investigate the factors associated with the
      treatment of hypertension among older adults living in the community. All
      residents (n = 1,742) of Bambui, Minas Gerais State, Brazil (15,000 inhabitants)
      aged > or = 60 years were selected, and 1494 (85.8%) were interviewed and
      examined. Of these, 919 (61.5%) were hypertensive, 704 were aware of their
      condition (study population), and 578 were under treatment. Only 38.8% of the
      individuals under treatment presented controlled systolic and diastolic pressures
      (< 140 and < 90 mmHg, respectively). Independent associations with treatment of
      hypertension were found for, in decreasing order of magnitude: less time elapsed
      since the last blood pressure measurement, greater number of physician visits in
      the past 12 months, higher body mass index, female gender, history of coronary
      disease, changes in diet due to arterial hypertension, and higher family income.
      Our results show that the factors most strongly associated with treatment of
      hypertension (use of health services) could be modified through adequate health
      policies for older adults.

PMID- 12806485
TI  - Biomedical factors associated with hospitalization of older adults: The Bambui
      Health and Aging Study (BHAS).
AB  - The objective of this study was to identify biomedical factors (body mass index,
      blood pressure, blood glucose, total cholesterol and fractions, triglycerides,
      and albumin) associated with hospitalization of older adults. All residents of
      the town of Bambui, Minas Gerais State, ages > or = 60 years (n = 1,742) were
      selected for the study, of whom 1,494 (85.2%) participated. None of the
      biomedical factors studied was independently associated with occurrence of 1
      hospitalization during the previous 12 months. Body mass index < 20 Kg/m and
      total cholesterol = 200-263 mg/dl and > or 264 mg/dl were independently
      associated with > or = 2 hospitalizations. The introduction of biomedical factors
      did not modify the previously identified associations between hospitalization and
      indicators constructed from information obtained in a questionnaire survey. The
      results show that data easily obtained through interviews can be useful both for
      identifying older adults at risk of hospitalization and thus for assisting in
      prevention.

PMID- 12806486
TI  - [Approach to the elderly in family health programs].
AB  - This article discusses the role of the Brazilian National Policy for Senior
      Citizens' Health in the promotion of healthy aging, preservation and improvement
      of functional capacity in the elderly, disease prevention, recovery of those who
      fall ill, and rehabilitation of those with limited functional capacity, will the
      goal of ensuring that senior citizens can remain in their surroundings and
      independently exercise their functions in society. Care for the elderly should be
      based primarily on the family, with support from primary health care services,
      under the family health strategy, representing a link between the elderly and the
      health system. The article goes on to list some health problems among the elderly
      in which family health programs can have a major impact. The Family Health
      Strategy in Brazil is analyzed in relation to health care for the elderly, along
      with the responsibilities, skills, and attributions required by the health care
      team.

PMID- 12806487
TI  - [An anthropological approach to senior citizens' health issues].
AB  - This paper discusses the specificity of the anthropological approach to aging.
      The theoretical framework is introduced and illustrated by presenting studies
      carried out in different societies. These studies describe a great diversity of
      forms of aging and experiences relative to growing old that allow us to
      distinguish two kinds of elements that influence aging: those inherent to aging
      as a biological process and those directly associated with the characteristics of
      the individual, the social dynamics, and prevailing public policies in each
      society. The anthropological approach considers the interaction between these two
      groups of factors.

PMID- 12806488
TI  - Addressing social and gender inequalities in health among seniors in Canada.
AB  - Although canadian seniors enjoy economic security and good health and have made
      substantial gains in recent decades, this well-being is not equally shared among
      socioeconomic groups and between men and women. As for younger age groups, income
      predicts health status in later life, but less powerfully. Potential alternative
      explanations include an overriding influence of the aging process, the subjective
      effects of income loss at retirement and the attenuation of the poverty gap owing
      to public retirement income. Older women are more likely to age in poverty than
      men, to live alone and to depend on inadequately resourced chronic health care
      and social services. These differences will hold as well for the next cohort of
      seniors in Canada. Addressing these disparities in health requires a
      comprehensive, multisectoral approach to health that is embodied in Canada's
      population health model. Application of this model to reduce these disparities is
      described, drawing upon the key strategies of the population health approach,
      recent federal government initiatives and actions recommended to the government
      by federal commissions.

PMID- 12806489
TI  - [Dependent seniors: families and caregivers].
AB  - This article focuses on health care for dependent seniors in relation to chronic
      illnesses. Expectations about family support for the dependent elderly are
      related to the role of family caregivers, but care requires support from the
      public and private sectors. Governments throughout the developed countries are
      examining their role in the provision of social welfare programs, especially in
      the public health sector. To recommend home care and family assistance, the
      context of changing family structures, the type of care needed, and professional
      follow-up must be taken into account.

PMID- 12806490
TI  - Neurological examination in the healthy term newborn.
AB  - We carried out a cross-sectional study with a sample of 106 normal full-term
      newborns examined within 24 to 72 hours of birth. The following findings were
      evaluated: head and chest measurements, muscle strength, tone, tendon reflexes,
      superficial reflexes, primitive reflexes, and cranial nerves. All 106 newborns
      were considered neurologically normal. We found no differences in the
      neurological examination findings for newborns with different gestational ages.
      Primitive reflexes and appendicular tone in newborns examined at earlier
      postnatal ages tended to be less intense. We were able to determine the
      prevalence of certain neurological examination findings for the normal newborn
      and to discuss some differences between our results and those of other studies.
      Prevalence estimations for the different findings in our study may be valid for
      different populations as long as the same methodology is adopted.

PMID- 12806491
TI  - Do environmental influences alter motor abilities acquisition? A comparison among
      children from day-care centers and private schools.
AB  - Development occurs in a proper rhythm as result of genetic inheritance and
      environment factors. This study had the aim to identify some environmental risk
      factors for the motor development in two groups of healthy children. 100 pre
      school aged (five years children) from two day-care centers and a private school
      were evaluated, in Recife-PE. All the children underwent to a motor skills
      assessment and their parents answered a questionnaire. The children from the
      public nursery remained behind in fine motor skills. The results showed that the
      biologically healthy children development can suffer negative influence of the
      environmental risk factors. In this research these factors were: the father
      absence, improper toys use to the correct age, the place were the child was kept
      in the early childhood, the lack of pedagogical guidance and extra-parental
      socialization and low familiar socioeconomic status.

PMID- 12806492
TI  - Genetic and neurological evaluation in a sample of individuals with pervasive
      developmental disorders.
AB  - With the aim of analyzing which complementary tests are relevant in the
      diagnostic evaluation of individuals with pervasive developmental disorders, a
      protocol of clinical and laboratory evaluation was applied in 103 outpatients.
      The protocol included chromosomal analysis, screening for inborn errors of
      metabolism, cytogenetic and molecular study of the FRAXA, FRAXE, and FRAXF
      mutations, EEG, SPECT, and magnetic resonance imaging study. Eighty-four subjects
      concluded the complementary tests and were classified either as having autism,
      atypical autism or Asperger syndrome according to the DSM-IV criteria. Sixteen
      individuals, all bellonging to the two autistic groups, presented genetic or
      enviromental factors that may have lead to the behavioral disorders, showing the
      importance of diagnostic evaluation in this group of conditions. Neuroimaging and
      EEG findings were non-specific and occurred in similar proportion among the
      groups, being considered of relative low significance in the diagnostic
      evaluation of individuals with pervasive developmental disorders.

PMID- 12806493
TI  - Autism and Mobius sequence: an exploratory study of children in northeastern
      Brazil.
AB  - The psychiatric examination was performed with diagnostic instruments for autism
      (DSM-IV and Childhood Autism Rating Scale-CARS) in 23 children with Mobius
      sequence. From the 23 patients studied with Mobius sequence, five (26.1%) met the
      diagnostic criteria for infantile autism according DSM-IV and two (8.6%), under
      two years old, showed autistic-like behavior. The scores for six children were
      compatible to severe autism symptoms according CARS and one child met the
      criteria for moderate autism symptoms. Among five children with autism, three
      (60%) had positive history of misoprostol exposure during the first trimester of
      pregnancy and from two cases autistic-like, one (50%) had positive history of
      misoprostol exposure during pregnancy. According to our data, this is the first
      report of Mobius sequence with autism and positive history of misoprostol use
      during pregnancy.

PMID- 12806494
TI  - Time of presentation of stroke patients in Sao Paulo Hospital.
AB  - With the advent of time-dependent thrombolytic therapy for ischemic stroke it has
      become increasingly important for stroke patients to arrive at the hospital
      quickly. This study investigated the time that our patients took since the
      recognition of the symptoms until the stroke diagnosis in a hospital in the city
      of S o Paulo. We concluded that in our hospital medical personnel and paramedics
      did not consider stroke as a medical emergency before neurological evaluation.
      Social problems as lack of access to an effective emergency medical service are
      another important factor that was responsible for patient's delay. Our study was
      important in order to identify the problems that stroke patients face in our
      country until the diagnosis is established.

PMID- 12806495
TI  - Study comparing the stroke unit outcome and conventional ward treatment: a
      randomized study in Joinville, Brazil.
AB  - BACKGROUND AND PURPOSE: To assess the impact of a stroke unit (SU) on acute phase
      treatment when compared to a conventional general ward treatment (GW). METHOD:
      Seventy-four patients with acute stroke were randomized between a SU and
      conventional general ward (GW). We compared both groups regarding the length of
      hospital stay, lethality and functional and clinical status within 6 months,
      using the Scandinavian scale and Barthel index. RESULTS: Thirty-five and thirty
      nine patients were allocated at SU and GW, respectively. Lethality on the 10th
      day at SU and GW achieved 8.5% and 12.8% respectively (p= 0.41), whereas 30-days
      mortality rates achieved 14.2% and 28.2% (p= 0.24), 17.4% and 28.7% on the 3rd
      month (p= 0.39), and 25.7% and 30.7% on the 6th month (p= 0.41). Thirty-day
      survival curve achieved 1.8 log rank (p= 0.17), with a trend for lower lethality
      in the SU. In order to save one death in 6 months in SU, NNT (the number need to
      treat) was 20; to get one more home independent patient NNT was 15. No
      significant difference was found between the length of hospital stay and
      morbidity. CONCLUSION: No significant benefit was found in SU patients compared
      to GW group. However,an evident benefit in absolute numbers was observed in
      lethality, survival curve and NNT in thirty days period after stroke. Further
      collaborative studies or incresead number of patients are required to define the
      role of SU.

PMID- 12806496
TI  - Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
AB  - This study was done to evaluate the long-term patient's satisfaction after carpal
      tunnel syndrome (CTS) electrodiagnostic done between 1989 and 1994 (5 to 10 years
      follow-up). Mail contact was made to 528 consecutive cases with a questionnaire
      to be filled; 165 patients responded after 19 exclusions. CTS severity was graded
      from 0 (incipient) to 4 (severe) after a combination of median sensory distal
      latency, sensory median-radial latency difference and amplitude of the median
      compound muscle action potential. Current symptoms ("cure", improved, unchanged
      or worsed) and the therapy utilized, either surgical or conservative, were
      analyzed to the initial CTS severity, age and duration of symptomatology.
      Surgical release was done in 114 cases (69%). Patient's satisfaction after
      surgical and non-surgical were respectively, 77.6% and 16% ("cure"), 13.6% and
      52% (much improved), 5.4% and 9.3% (little improved), 2.7% and 16% (unchanged),
      0.7% and 6.7% (worsed). The frequency of "cure" versus unchanged/worsed or
      "cure"/much improved versus unchanged/worsed was highly significative (Fisher, P
      value < 0.001) and was not influenced by the CTS electrophysiological severity.
      There was no relationship between the outcome after surgery and duration of
      symptomatology, age or CTS severity. Conservative benefice was more prevalent in
      those with shorter symptomatology and older age; the majority of conservative
      failure cases had mild initial CTS. We concluded the excellent surgical benefice
      described by patients and the absence of any predictive factors based on CTS
      severity, age or duration of symptomatology for outcome.

PMID- 12806497
TI  - Adult cerebellar medulloblastoma: CT and MRI findings in eight cases.
AB  - Medulloblastoma is a brain tumor of neuroepithelial origin, which represents 15
      to 30% of all pediatric brain tumors, and less than 1% of CNS adult neoplasms. We
      report the imaging findings of 8 adult patients with medulloblastoma. The mean
      age was 35 years, ranging from 20 to 65 years, and the male:female rate was 3:5.
      The tumors were predominantly lateral (63%), hyperdense on CT scans (83%), and on
      the MRI, hypointense on T1 (100%) and hyperintense on T2 (80%) weighted images.
      It was seen intratumoral necrosis and cysts in six cases and calcifications in
      three. Hydrocephalus was observed in 5 cases and brain stem invasion in four. The
      imaging findings of medulloblastomas in adults are different of those in child,
      and also nonspecific. Although these tumors are uncommon in adults, they must be
      considered in the differential diagnosis of cerebellar masses in the posterior
      fossa of this age group.

PMID- 12806498
TI  - Endoscopic approach to fourth ventricle cysticercosis.
AB  - Neurocysticercosis is the most frequently observed parasitosis of the central
      nervous system worldwide. The fourth ventricle is the most frequent site of
      intraventricular infestation, a location that carries a higher risk for CSF
      blockage and intracranial hypertension due to CSF blockage. A great number of
      patients become shunt dependent which carries a poorer prognosis. We report on a
      case of a patient with symptomatic obstructive hydrocephalus due to cysticercus
      in the fourth ventricle where an endoscopic approach via a frontal burr hole was
      performed. Although there is no consensus in the literature for the optimal
      treatment of this disease, this method seemed adequate for treatment of fourth
      ventricle cysticercosis in patients with hydrocephalus, aqueductal and foramen of
      Monro dilatations.

PMID- 12806499
TI  - Mast cell subsets and neuropeptides in leprosy reactions.
AB  - The immunohistochemical identification of neuropeptides (calcitonin gene-related
      peptide, vasoactive intestinal polypeptide, substance P, alpha-melanocyte
      stimulating hormone and gamma-melanocyte stimulating hormone) quantification of
      mast cells and their subsets (tryptase/chymase-immunoreactive mast cells = TCMC
      and tryptase-immunoreactive mast cells = TMC) were determined in biopsies of six
      patients with leprosy reactions (three patients with type I reaction and three
      with type II). Biopsies were compared with those taken from the same body site in
      the remission stage of the same patient. We found a relative increase of TMC in
      the inflammatory infiltrate of the reactional biopsies compared to the post
      reactional biopsy. Also, the total number of mast cells and the TMC/TCMC ratio in
      the inflammatory infiltrate was significantly higher than in the intervening
      dermis of the biopsies of both periods. No significant difference was found
      regarding neuroptide expression in the reactional and post-reactional biopsies.
      The relative increase of TMC in the reactional infiltrates could implicate this
      mast cell subset in the reported increase of the immune response in leprosy
      reactions.

PMID- 12806500
TI  - Regional differences in the number and type of myenteric neurons in the
      descending colon of rats.
AB  - The purpose of this study was to analyze the neuronal density of the myenteric
      plexus of the intermediate and antimesocolic regions of the descending colon of
      rats. Whole-mounts were stained with three different techniques of neuronal
      evidenciation. Through counts of the number of neurons in an area of 6.64 mm
      under light microscopy, we found 1,271 +/- 227.54 neurons with Giemsa in the
      intermediate region and 1,234 +/- 225.92 neurons in the antimesocolic region;
      with the NADH-diaphorase technique we found 530 +/- 92.97 neurons in the
      intermediate region and 539 +/- 146.72 neurons in the antimesocolic region; and
      through the NADPH-diaphorase histochemistry, we found 417 +/- 34.42 neurons in
      the intermediate region and 547 +/- 84.01 neurons in the antimesocolic region. We
      conclude that there is a variation in the density of NADPH-diaphorase positive
      neurons in the intestinal circumference; that the NADH-diaphorase positive
      neuronal subpopulation represented 42.7% of that stained with Giemsa; and that
      the NADPH-diaphorase positive neurons represented 37.8% of the whole myenteric
      population.

PMID- 12806501
TI  - Effect of protein and vitamin B deficiency on the morpho-quantitative aspects of
      the myenteric plexus of the descending colon of adult rats.
AB  - We carried out this work with the purpose of studying the effects of protein and
      vitamin B deficiency on the morphologic and quantitative aspects of the myenteric
      plexus of the descending colon of adult Rattus norvegicus. Twenty-eight rats were
      divided in two groups, one of them receiving chow with 22% protein level
      (control) and the other fed with chow having 8% protein level without vitamin B
      supplementation, during 120 days. Whole-mounts of the descending colon were
      prepared and stained with Giemsa, NADH-diaphorase and NADPH-diaphorase. The
      undernourished rats had a body weight 11.84% less than the control group.
      Relative to the controls, the experimental group had a colonic area 48% smaller,
      51.9% less Giemsa-stained neurons, 28.3% less NADH-diaphorase positive neurons
      and 24.2% less NADPH-diaphorase positive neurons.

PMID- 12806502
TI  - [Experimental tumors of the central nervous system: standardisation of a model in
      rats using the 9L glioma cells].
AB  - A number of experimental models have been established during the last decades in
      order to study tumor biology and the effects of treatment or manipulation of the
      microenvironment of malignant glial tumors. Even though those models have been
      well characterised and are, to a certain extent, easily reproducible, there are
      limitations as to their use and to the interpretation of the results. The aim of
      this study is to standardize a model of a malignant glial tumor and detect
      possible events able to modify its development. 9L cells were inoculated
      intracerebrally in 48 Sprague-Dawley rats; from these, 25 animals were also
      implanted with a device containing electrodes for the registration of the
      electroencephalogramm. Animals were daily evaluated by neurologic examination.
      Twenty four animals developed tumor - 10 animals died either in the immediate pos
      operatory period or during evolution; 14 animals did not develop tumor.
      Macroscopically the tumor was well demarcated from the adjacent brain; by light
      microscopy the tumor exhibited malignant characteristics as well as extensive
      infiltration of the brain parenchyma. Diagnosis was that of a malignant
      astrocytoma. The use of the stereotaxic frame and care to infuse a small volume
      of liquid containing cells during a period of 120 seconds were the most important
      procedures to obtain sucess in the model. Additional care should be taken in
      counting cells in the Neubauer camera and in maintaining cells in constant
      agitation before injecting the tumor-containing solution. The model here
      developed was efficient besides being of low cost and of relatively easy
      execution.

PMID- 12806504
TI  - [Horner syndrome after stereotactic Parkinson disease surgery].
AB  - We present ten patients with Parkinson's disease who underwent stereotactic
      ablative radiofrequency procedures. Seven patients underwent pallidotomy, two
      subthalamotomy and VIM, and one subthalamotomy. Seven developed miosis and all
      semiptosis ipsilateral immediately after the procedure. The occurrence of
      Horner's syndrome is probably due to the lesion of sympathetic fibers among
      hypothalamus, Forel's field and thalamus after the stereotactic procedure.

PMID- 12806503
TI  - [Prognostic factors in the treatment of the intradural extramedullary tumors: a
      study of 44 cases].
AB  - Between 1993 and 1999, 44 patients submitted to resection of an expansible
      intradural extramedullary lesion who filled protocol requirements of appropriate
      follow up were studied. Patients were constituted by 43.2% female and 56.8% male.
      The mean age was 32.9 years old. Lesion most common location was at the thoracic
      spine, with 45.5% of the cases, followed by the lumbar level with 18.2%. Tumor
      extension varied from 1 to 7 vertebral segments, with an average of 2.5 levels.
      Schwannoma, with 65,9% of the cases, was the most frequent lesion, followed by
      meningioma with 20.5%. There were 2 cases of neurofibroma and 1 case of
      paraganglioma, neuroenteric cyst, metastasis and malignant schwannoma. The
      evolution was of improvement in 56.8%, stability in 31.8% and of worsening in
      11.4%. There was no mortality related to the surgical procedure. All cases of
      worsening had total resection and they had lesions located in the thoracic
      segment. Total resection is the ideal modality of surgical treatment. However, at
      the thoracic level, where the peculiarities of spine irrigation prevail, surgical
      morbidade may be higher (p=0.014).

PMID- 12806505
TI  - [A comparative study of the perceptual and motor performance at school age of
      preterm and full term children].
AB  - The objective of this study was to compare the perceptualmotor performance in
      school age children who were born preterm and full term. Two groups of children,
      ages 5 to 7, participated in this study. Group I had 35 children, from low-income
      families, born up to the 34 week of gestation and/or weight bellow 1500 g. Group
      II had 35 full-term children, matched by age, gender and socioeconomic status to
      the children in Group I. Children were tested on the Bender gestalt, the motor
      accuracy test and on balance and postural responses measures. The preterm group
      obtained significantly lower scores in the majority of the tests. These besides
      reinforcing the importance of the follow-up of preterm children up to school age,
      also indicate the need to stimulate the fine motor and postural control Devment,
      even among preterm children who do not show evidence of neurological impairment.

PMID- 12806506
TI  - Botulinum toxin for treatment of Frey's syndrome: report of two cases.
AB  - Frey's syndrome is a phenomenon of hemifacial flushing and sweating after
      gustatory stimulus, usually secondary to surgical trauma over the parotid gland,
      although other injury mechanisms may be seen. It is accepted as a result of
      aberrant regeneration of facial autonomic nerve fibers. Treatment evolved from
      ineffective medical and surgical approaches to botulinum toxin. We evaluate the
      effectiveness and safety of botulinum toxin in the treatment of this complication
      in two patients.

PMID- 12806507
TI  - Disseminated cerebral thrombotic microangiopathy in a patient with adult's still
      disease.
AB  - OBJECTIVE: The aim of this report is to describe a fatal disseminated thrombotic
      micoangiopathy with renal, pancreatic, and cerebral involvement in a patient with
      recently diagnosed adult's Still disease (ASD). CASE REPORT: A previously healthy
      15 year old girl was admitted to our hospital. According to the clinical and
      laboratory data the diagnosis of adult's still Disease was established. The
      treatment was begun and few days after an initial improvement a sudden neurologic
      deterioration with coma and seizures has occurred. Hours later the patient died.
      Clinical, laboratorial, and pathologic data will be presented. CONCLUSION: To our
      knowledge this is the second description of a fatal disseminated cerebral
      thrombotic microangiopathy in a patient with adult's Still disease, but with a
      much more fulminating evolution than previously reported. Some etiopathogenic
      mechanisms could be shared in these two disorders explaining this coexistence.

PMID- 12806508
TI  - Myotonia congenita and myoadenylate deaminase deficiency: case report.
AB  - Approximately 1-2% of the population has a deficiency of the enzyme myoadenylate
      deaminase. Early reports suggested that patients with myoadenylate deaminase
      deficiency had various forms of myalgia, and exercise intolerance. However, a
      deficiency of the enzyme has been described in many conditions, including
      myopathies, neuropathies, and motor neuron disease. We report a patient with
      clinical diagnosis of myotonia congenita and absent myoadenylate deaminase
      reaction on the muscle biopsy. This is the first description of myoadenilate
      deaminase deficiency with myotonia congenita. Myoadenylate deaminase deficiency
      is the most common enzymatic deficit of muscle, and the association with other
      neuromuscular diseases is coincidental.

PMID- 12806509
TI  - Early-onset acute transverse myelitis following hepatitis B vaccination and
      respiratory infection: case report.
AB  - Acute transverse myelitis is an acute inflammatory process of the spinal cord and
      it is a rare clinical syndrome in childhood. In this paper, we report a case of 3
      years-old boy who developed acute onset tetraparesia following a viral
      respiratory infecction and hepatitis B vaccination. Magnetic resonance imaging of
      the spinal cord disclosed signal-intensity abnormalities from C4 to C3. A
      diagnosis of acute transverse myelitis was made and the patient was treated with
      IV methylprednisolone and IV immunoglobulin. The child had a fair outcome despite
      of the very acute course of the disease and the presence of a cervical sensory
      level which usually harbor a poor prognosis.

PMID- 12806510
TI  - Lumbosacral angiolipoma: case report.
AB  - We present a case of a 46-year old woman with a ventral epidural angiolipoma at
      the lumbosacral level with erosion of the sacrum. About ninety cases of spinal
      angiolipomas have been previously described in the literature, most of them
      situated on the thoracic region, dorsal to the dural sac. Angiolipomas can be
      radically excised with a good prognosis even in the presence of bone erosion. We
      did not find any other angiolipoma at the sacral level surgically explored in the
      review of the literature.

PMID- 12806511
TI  - Posterior fossa gangliocytoma with facial nerve invasion: case report.
AB  - A 5 year-old boy with a cerebellar gangliocytoma with a peripheral right facial
      paresis and ataxia is presented. His MRI showed a heterogenous, diffuse lesion,
      isointense on T1 and hyperintense on T2-weigthed sequences, involving the right
      cerebellar hemisphere with direct extension into the right facial nerve. The
      present case is the first description of a gangliocytoma with direct facial nerve
      invasion, as demonstrated for the facial nerve paresis and supported by MRI and
      surgical inspection.

PMID- 12806512
TI  - [Meningioma with rhabdoid transformation: case report].
AB  - Meningiomas represent aproximatelly 30% of all intracranial tumors in autopsy
      studies. With an incidence of 2.3 per 100000, they are considered commom tumors
      in clinical practice. Twenty percent of the all intracranial tumors diagnosed in
      vivo are meningiomas. Most of these lesions are benign and the prognosis is
      intimatelly related to acessibility and ressectability of the lesion. Malignant
      meningiomas are rare lesions, representing between 1 to 11% of all meningiomas,
      varying with the definition of pathological criteria for malignancy used, and are
      categorized in atypical or malignant. Only recently rhabdoid transformation of
      meningiomas have been reported. We present a case of an extremelly aggressive
      rhabdoid meningioma in a 56 year-old woman. The tumor was surgically removed
      twice, with a lethal outcome due to local recurrence, despite maximum radiation
      and quimiotherapy, six months after the initial presentation.

PMID- 12806513
TI  - [Rathke's pouch cyst: case report].
AB  - The Rathke's pouch cysts are a relatively common autopsy finding, but rarely have
      they been reported as a clinical entity. We report a Rathke's pouch cyst
      patient's case with visual impairment and emphasize aspects like clinical
      presentation, radiological studies and treatment. Many published series about
      this pathology have been reviewed and compared with the present case.

PMID- 12806514
TI  - [Galen vein thrombosis: case report].
AB  - Cerebral venous thrombosis (CVT) is a vascular disease with many clinical
      manifestations and possible etiologies (local, systemic or idiopathic). Galen
      vein thrombosis (GVT) is a rare cause of CVT and usually it is associated with
      some vascular malformation. We report a case of a 16 years old female patient
      with GVT without vascular malformation, but associated with straight sinus
      thrombosis and venous thalamic infarct. Relevant aspects of the clinical,
      radiological and laboratory diagnosis of CVT are also discussed.

PMID- 12806515
TI  - [Surgical treatment of meralgia paresthetica: case report].
AB  - Meralgia paresthetica is characterized by pain, paresthesias or burning, and
      decreased touch and pain sensation on the anterolateral aspect of the thigh. It
      is due to neuropathy of the lateral femoral cutaneous nerve (LFCN). Conservative
      treatment is usually successful in relieving the symptoms in most of the
      patients. We describe a case of a woman, 37 years old, who required surgical
      treatment for intractable symptoms. Although neurolysis with transposition is the
      most common procedure, we preferred neurectomy with excision of a portion of the
      LFCN for its very low recurrence rate as opposed to neurolysis. The area of
      anesthesia generated by this procedure in the distribution of the LFCN tends to
      shrink with time. This patient achieved excellent outcome following this surgical
      technique.

PMID- 12806516
TI  - [Inside-outside occipito-cervical fixation: technical report].
AB  - The clinical knowledgement of biomechanics of atlantoaxial complex have been
      proved that progressive instability has a mandatory occurrence after anterior
      decompression of the craniocervical junction. We report the occipitocervical
      fixation so called inside-outside technique, originally described by Pait et al.
      appliedin in two patients whom underwent odontoidectomy. The occipitalcervical
      fixation technique consist in the use of a titanium rod bended according with
      occipital cervical angle placed and fixed laterally over the cervical spine. The
      rod is fixed to the occipital bone by mean of placement a screw which flat
      portion is positioned onto the epidural space. In the cervical spine the rod is
      attached to transarticular screws placed at the superolateral quadrant of the
      articular mass. In the axis the screw is introduced through the pars
      interarticularis finishing at the axis body or the lateral mass of the atlas.
      This technique proved to be safe and easily applied in the patients whom
      underwent this surgical procedure.

PMID- 12806517
TI  - [The cerebral protection technique in angioplasty plus stenting of carotid: an
      effective procedure against cerebral embolism].
AB  - OBJECTIVE: To describe the cerebral protection technique used in the angioplasty
      and stenting to treat stenotic lesions of carotid artery bifurcation, showing its
      efficiency in avoiding cerebral emboli during the procedure. METHOD: Forty two
      patients (47 arteries) were treated with the cerebral protection technique, which
      consists in the temporary occlusion of the internal carotid artery, above the
      stenotic lesion, performing the aspiration and flushing of glucose solution into
      the internal carotid artery after the delivery of the stent and the angioplasty,
      to remove any atherosclerotic plaque's fragments. RESULTS: The angioplasty was
      efficient in all cases. There were no cerebral emboli in the patients in whom the
      complete cerebral protection technique was used, showing its efficiency. Distal
      embolism occurred in one patient, during pre angioplasty and before the use of
      cerebral protection. CONCLUSION: The cerebral protection technique was efficient
      to avoid cerebral emboli in the procedures performed. This data is in agreement
      with the literature and the use of this technique increases the indications of
      carotid angioplasty.

PMID- 12806518
TI  - [Suction-irrigator device for microsurgery: technical note].
AB  - A modification of the conventional suction device for microsurgery is described.
      It consists of a built-in tube in another tube, being the first connected to the
      suction device and the second to the irrigation. This suction-irrigator device
      allows to accomplish the suction and irrigation simultaneously and in a precise
      way.

PMID- 12806519
TI  - [Landmarks to the cranial approaches].
AB  - The knowledge of the craniotopography allows the delimitation of the cranial
      approaches. In this study the landmarks, defined in relation to the craniometric
      points and used in the different cranial approaches, were systematized. Twenty
      two landmarks are described: the first twelve are in relation to the skull base
      and the remainder are in relation to the skull vertex.

PMID- 12806520
TI  - Expensive cerebral blood flow measurements alone are useless and misinformative
      in comatose patients: a comprehensive alternative.
AB  - Since the first report addressing quantification of cerebral blood flow (CBF),
      concomitant assessment of cerebral oxygen consumption was also carried out. Over
      the years, however, some investigators have emphatically and mistakenly addressed
      cerebral ischemia in comatose patients, on the basis of CBF measurements alone.
      In contrast, we have repeatedly reported that ischemia in these patients must be
      precisely evaluated based on CBF-metabolism coupling or uncoupling, rather than
      CBF alone. Based on these previous findings, we therefore propose a comprehensive
      alternative approach, namely the evaluation of brain ischemia in comatose
      patients based on cerebral metabolic parameters, such as cerebral extraction of
      oxygen or cerebral lactate release, without expensive CBF measurements.

PMID- 12806521
TI  - The triptan formulations: a critical evaluation.
AB  - The migraine-specific triptans have revolutionized the treatment of migraine and
      are usually the drugs of choice to treat a migraine attack in progress. Different
      triptans are available in different strengths and formulations including oral
      tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections.
      In Europe, sumatriptan is also available as a suppository. Specific differences
      among the triptans exist as evidenced by different pharmacological profiles
      including T1/2, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles,
      amongst other parameters. How or whether these differences translate to clinical
      efficacy and tolerability differences is not well differentiated. Clinical
      distinctions among these agents are subtle and proper choice of triptan requires
      attention to the specific characteristics of each individual patient, knowledge
      of patient preference, accurate history of the efficacy of previous acute care
      medications as well as individual features of the drug being considered. Delivery
      systems may play an important role in the onset of action of triptans. The
      selection of an acute antimigraine drug for a patient depends upon the
      stratification of the patient's migraine attack by peak intensity, time to peak
      intensity, level of associated symptoms such as nausea and vomiting, time to
      associated symptoms, comorbid diseases, and concomitant treatments that might
      cause drug-drug interactions. The clinician has in his armamentarium an ever
      expanding variety of medications, available in multiple formulations and dosages,
      with good safety and tolerability profiles. Continued clinical use will yield
      familiarity with the various triptans, and it should become possible for the
      interested physician to match individual patient needs with the specific
      characteristics of a triptan to optimize therapeutic benefit.

PMID- 12806522
TI  - The vast "underbelly" of new technology.

PMID- 12806523
TI  - Removal of esophageal expandable metal stents: description of technique and
      review of potential applications.
AB  - BACKGROUND: Expandable metallic stents (EMS) have seen wide application in
      patients with malignant stricture and fistulas. They have not seen wide
      application for benign disease because of concern over acute complications and
      long-term sequelae. METHODS: Between June 1999 and October 2000, six patients
      with EMS in place for malignant stricture (n = 3), benign stricture (n = 1),
      anastomotic leak (n = 1) and benign esophagorespiratory fistula (n = 1) had their
      stents endoscopically removed. Removal was performed secondarily to the following
      complications: secondary stricture (n = 1), epidural abscess (n = 1), diskitis (n
      = 1), resolution of fistula (n = 2), and resolution of anastomotic leak (n = 1).
      RESULTS: Four patients had one EMS: Ultraflex (n = 3) and Z-stent (n = 1). In two
      patients, two stents (Ultraflex and Z-stent) were retrieved simultaneously. No
      procedurally related complications occurred. Two patients with esophageal cancer
      required additional stents. All three patients with benign fistula and stricture
      recovered uneventfully. CONCLUSIONS: The safe removal of current brands of EMS
      may facilitate the wider application of these devices to include selective
      patients with benign disease.

PMID- 12806524
TI  - The significance of pH and manometric testing after laparoscopic fundoplication.

PMID- 12806525
TI  - Decompressive colonoscopy with intracolonic vancomycin administration for the
      treatment of severe pseudomembranous colitis.

PMID- 12806526
TI  - CIRSE 2003. Abstracts of the annual meeting of the Cardiovascular and
      Interventional Radiological Society of Europe.

PMID- 12806527
TI  - Gender matters: constructing a model of adolescent sexual health.
AB  - This article illustrates the construction of a new model of adolescent sexual
      health, one that addresses the complex relationships between gender and
      adolescent sexuality. A review of sexual health models highlights the absence of
      gender; in contrast, research illuminates the significance of gender. This
      article describes the process of building a model of sexual health explicitly for
      girls, guided by feminist research on adolescent girls' sexuality and a "web of
      theories". It also describes the unanticipated challenges of making a companion
      model for boys and the ensuing shift from a gender-specific approach to an
      integrated gendered model of adolescent sexual health. Gender complementarity is
      defined and forwarded as a way to incorporate gender into a model of adolescent
      sexual health.

PMID- 12806528
TI  - Sexual double standards: a review and methodological critique of two decades of
      research.
AB  - A review of 30 studies published since 1980 found evidence for the continued
      existence of sexual double standards: different standards of sexual
      permissiveness for women and men. Experimental studies have included
      predominantly White North American college students; ethnographies, focus group
      and interview studies, and linguistic analyses have included more diverse
      samples. Studies show that sexual double standards are influenced by situational
      and interpersonal factors (e.g., the target's age, level of relationship
      commitment, and number of partners), and that double standards are local
      constructions, differing across ethnic and cultural groups. This review discusses
      methodological issues, including the strengths and limitations of quantitative
      and qualitative approaches. It also discusses implications for women s high-risk
      sexual behavior and sexual identity, and suggests directions for future research.

PMID- 12806529
TI  - Truth and consequences: using the bogus pipeline to examine sex differences in
      self-reported sexuality.
AB  - Men report more permissive sexual attitudes and behavior than do women. This
      experiment tested whether these differences might result from false accommodation
      to gender norms (distorted reporting consistent with gender stereotypes).
      Participants completed questionnaires under three conditions. Sex differences in
      self-reported sexual behavior were negligible in a bogus pipeline condition in
      which participants believed lying could be detected, moderate in an anonymous
      condition, and greatest in an exposure threat condition in which the experimenter
      could potentially view participants responses. This pattern was clearest for
      behaviors considered less acceptable for women than men (e.g., masturbation,
      exposure to hardcore & softcore erotica). Results suggest that some sex
      differences in self-reported sexual behavior reflect responses influenced by
      normative expectations for men and women.

PMID- 12806530
TI  - Single and double sexual standards in Finland, Estonia, and St. Petersburg.
AB  - The sexual revolution and fight for gender equality began in the West during the
      1960s but did not reach the Soviet Union until the late 1980s. Using survey data
      from nationally representative samples from Finland in 1971, 1992, and 1999 and
      from two former Soviet areas, Estonia in 2000 and St. Petersburg in 1996, we
      investigated the following: (a) differences across decades and countries in
      acceptance of the sexual double standard (SDS) in attitudes toward marital
      infidelity and women's initiating sex; and (b) the relationship between the SDS
      and sexual satisfaction. Results show that Finland in the 1990s was more
      egalitarian than Finland in 1971, St. Petersburg in 1996, or Estonia in 2000.
      Egalitarian sexual attitudes were positively related to sexual satisfaction.

PMID- 12806531
TI  - Sexual decision making and safer sex behavior among young female injection drug
      users and female partners of IDUs.
AB  - Data from interviews with 94 young women who were injection drug users (IDUs) or
      partners of IDUs were analyzed to examine associations between self-reported
      sexual decision making and condom use, contraceptive use, and relationship
      characteristics. Most women (73-85%) reported participating in decisions about
      condom use, contraception, and when to have sex. Adjusting for potential
      covariates, respondents who reported participating in decisions about condom use
      and when to have sex were 7 and 19 times, respectively, more likely than others
      to report recently using condoms. Respondents who reported participating in
      decisions about contraception were 20 times more likely than others to report
      recently using contraceptives. Longer sexual relationships were associated with
      decreased likelihood of condom or contraceptive use.

PMID- 12806532
TI  - "Just trying to relax": masculinity, masculinizing practices, and strip club
      regulars.
AB  - This article explores customers' understandings of their visits to heterosexual
      strip clubs and the ways in which those visits become meaningful to them in
      relation to cultural discourses around masculinity, sexuality, leisure, and
      consumption, as well as in relation to their everyday lives and relationships.
      Not every man finds strip clubs pleasurable, yet understanding why some men
      frequent these venues can inform us more generally about the links between
      sexuality, gender, and the marketplace. This article focuses on regular male
      customers' stated motives for visiting strip clubs and examines those visits as
      touristic and masculinizing practices. It also explores gender, sexuality, and
      power in the men s performances of desire in the clubs, taking up issues of
      visibility, virility, youthfulness, and commodification.

PMID- 12806533
TI  - Tactics of sexual coercion: when men and women won't take no for an answer.
AB  - We investigated women's and men's reports of experiencing and using tactics of
      postrefusal sexual persistence, defined as persistent attempts to have sexual
      contact with someone who has already refused. Participants were 275 men and 381
      women at Midwestern and Southern universities. More women (78%) than men (58%)
      reported having been subjected to such tactics since age 16; this difference was
      significant for the categories of sexual arousal, emotional manipulation and
      lies, and intoxication, and for two tactics within the physical force category
      (physical restraint and threats of harm). More men (40%) than women (26%)
      reported having used such tactics; this difference was significant for the sexual
      arousal, emotional manipulation and lies, and intoxication categories. We present
      participants' written descriptions of their experiences.

PMID- 12806534
TI  - Sexual compliance: gender, motivational, and relationship perspectives.
AB  - This paper provides a systematic review of research on sexual compliance in
      heterosexual relationships. Three perspectives shed light on which individuals
      are the most likely to comply with a sexually interested partner's desire for sex
      and why. A gender perspective highlights the common male-female asymmetry in
      compliant sexual behavior and identifies factors that contribute to women's
      greater likelihood of being the sexually compliant partner. A motivational
      perspective distinguishes between approach and avoidance motives for compliance
      and considers the possible consequences of these motives for emotional reactions,
      sexual risk taking, and sexual violence. A relationship maintenance perspective
      views sexual compliance as illustrative of broader patterns of sacrifice in
      committed relationships. Each perspective suggests important new directions for
      empirical research.

PMID- 12806535
TI  - Sibling influence, gender roles, and the sexual socialization of urban early
      adolescent girls.
AB  - This study examined whether older siblings influence early adolescent girls'
      sexual socialization. Participants were 180 girls, 12 to 14-years-old, from
      predominantly ethnic minority backgrounds. They completed a battery of
      interviewer-administered measures assessing a range of sexual cognitions and
      romantic and sexual behaviors. As predicted, compared with other girls, girls
      with older brothers placed greater value in becoming a parent, had lower levels
      of sexual responsivity or interest, and reported smaller age discrepancies
      between themselves and their partners for their first romantic kiss. Regardless
      of sibling sex, having older siblings was associated with more restrictive sexual
      cognitions and behaviors. Findings are interpreted in the context of sexual
      script theory.

PMID- 12806536
TI  - [Treatment of chronic hepatitis C with PEG-interferon alpha-2b and ribavirin: 24
      weeks of therapy are sufficient for HCV genotype 2 and 3].
AB  - Patients with chronic hepatitis C infected with HCV genotype 2 and 3 can be
      successfully treated in more than 80 % of cases. It had been shown that a 24 week
      t.i.w. treatment period with standard interferon alpha and ribavirin is
      sufficient for these patients. However, the recent multicenter studies
      investigating the effect of pegylated interferons and ribavirin used a 48 week
      schedule for all patients irrespective of the HCV genotype. Thus, we
      prospectively investigated the efficacy of a 24 week treatment period with
      pegylated interferon alpha-2b (1.0-1.5 microg/kg o.i.w.) and ribavirin (1-1.2 g
      daily) in 54 patients with HCV-genotype 2 and 3 at two different sites. 29
      patients were included in Herne (private practice) and 25 patients were treated
      in Hannover (Medical School). After the end of follow-up 46 (85%) patients showed
      a virological sustained response in the intent to treat analysis. Only four
      patients demonstrated a virological treatment failure (3 relapse, 1
      breakthrough), two patients were non-compliant, and at each center therapy was
      stopped in one patient due to adverse events. There was no difference regarding
      treatment response between both sites, even though the patients in Herne were
      treated only with 1,0 microg/kg PEG-IFN alpha-2b, while patients in Hannover
      received 1,5 microg/kg PEG-IFN alpha-2b. In conclusion, the response rates of
      this study do not differ from the results of the 48 week treatment period of the
      recently published multicentre trials. Thus, we suggest treating all patients
      with HCV-genotype 2 and 3 for only 24 weeks when PEG-IFN alpha-2b is used in
      combination with ribavirin.

PMID- 12806537
TI  - Socioepidemiological data on hepatitis delta in a German university clinic-
      increase in patients from Eastern Europe and the former Soviet Union.
AB  - BACKGROUND AND AIMS: The relevance of chronic hepatitis delta results from its
      high morbidity leading frequently to rapid cirrhosis progression. The aim of the
      present study was the socioepidemiological characterization of patients with
      hepatitis delta, in order to identify patients at risk for hepatitis delta.
      PATIENTS AND METHODS: Clinical parameters of 36 consecutive patients with chronic
      hepatitis delta, seen between 1989 and 2002 at the University Hospital in
      Dusseldorf, were evaluated for the present study. Socioepidemiological
      parameters, available in 31 of these patients who returned a questionnaire, were
      compared to data of the population of Nordrhein-Westfalen (NRW). RESULTS: Liver
      cirrhosis was found in 33.3% of patients. There was a mean delay of 3 years
      between the diagnosis of hepatitis B and D. Patients with delta hepatitis were
      characterized by lower education, were more frequently unemployed, exhibited less
      qualified work and had less property compared to the population of NRW. 86.1% of
      hepatitis delta patients were immigrants to Germany. Before 1995 hepatitis delta
      infections were mainly seen in patients from Southern Europe (75%), whereas after
      1996 predominantly patients from Eastern Europe and the former Soviet Union
      (53.6%; p < 0.04) contributed to the newly diagnosed cases of hepatitis delta.
      CONCLUSIONS: The present data underline that hepatitis delta is a severe disease.
      It seems reasonable to intensify screening for hepatitis delta among patients
      with low socioeconomic status, especially among immigrants of Eastern Europe and
      the former Soviet Union.

PMID- 12806538
TI  - [Costs of ambulant care for patients with inflammatory bowel disease in general
      practice].
AB  - BACKGROUND: Outpatient care managed by general practitioners plays an important
      role in diagnostic and treatment of inflammatory bowel diseases (IBD). The
      chronic recurrent course often requires intensive and costly medical care.
      OBJECTIVE: To measure the costs of outpatient care for patients with IBD provided
      by general practitioners (GPs). MATERIAL AND METHODS: The analysis is based on an
      electronic data base implemented in 100 general practices in different parts of
      Germany. 191 patients with altogether 705 consultations over a period of one year
      were included in the analysis. Costs of care were measured using German fee
      schedules for health care delivery and market prices for drugs. RESULTS: In a 12
      months-period the mean number GP-contacts was 3.6. Mean costs were 23.61 euro;
      per visit and annual costs were 87.15 euro; per patient. Pharmacotherapy was used
      by 147 patients (77%) and caused costs of 613.40 euro; per year, with 64% due to
      the use of salicylates. 66 patients (35%) also had diagnostic services provided
      from specialists, 7 patients (4%) required psychotherapeutic care. CONCLUSION:
      The presented study is the first to analyse in detail the costs for medical care
      of IBD in general practices in Germany. Results can be used in economic
      assessment of the disease and in cost-effectiveness-analyses of intervention
      strategies. They may support treatment guidelines and treatment decisions from an
      economic point of view.

PMID- 12806540
TI  - [Esophageal 24 hour-pH metry. Recommendations of the German Society of
      Neurogastroenterology and Motility and the Study Group for Gastrointestinal
      Functional Disorders and Function Diagnostics of the Austrian Society of
      Gastroenterology and Hepatology].
AB  - This article presents the recommendations for 24-hour oesophageal pH-metry of the
      German Society of Neurogastroenterology and Motility and the Study Group for
      Gastrointestinal Functional Disorders and Function Diagnostics of the Austrian
      Society of Gastroenterology and Hepatology. Indications for the examination, the
      procedures to be followed, the analysis of the obtained data and the conclusions
      to be drawn are delineated. The literature on which the recommendations are based
      is reviewed.

PMID- 12806541
TI  - [New ILCO-guideline. Hospital rehabilitation of stoma patients].

PMID- 12806542
TI  - Increasing sensitivity of morphological diagnosis in hepatocellular carcinoma
      (HCC) by combination of cytological and fine-needle histological examination
      after ultrasound guided fine needle biopsy.
AB  - Increasing sensitivity of morphological diagnosis by combination of cytological
      and fine-needle histological examination after ultrasound guided fine needle
      biopsy in hepatocellular carcinoma (HCC). AIM: We investigated the factors which
      may affect the sensitivity of morphological diagnostics (cytology and fine-needle
      histology) in HCC after ultrasound guided biopsy. METHOD: In 62 patients, an
      ultrasound guided cytological (n = 62) and fine-needle histological (n = 45)
      biopsy was performed. In addition, the smears were investigated by cytophotometry
      (n = 62). RESULTS: Considering each method separately, the sensitivity of both
      cytological and histological diagnostics was about 80%. The sensitivity could be
      raised to 89% by combining the two methods. In seven patients, the HCC could not
      be primarily confirmed morphologically. In nine patients, the result of
      histological and cytological investigation was not congruent. With regard to the
      size of the biopsied lesion, tumor stage, cytophotometric finding and survival
      these 16 patients (group A) were compared with the 46 patients in whom the HCC
      could be primarily confirmed morphologically (group B). The statistical analysis
      did reveal a significantly lower percentage of tumors with diploid or tetraploid
      (euploid) cells in group B. Euploid tumors were significantly more highly
      differentiated. In patients with euploid tumors, the sensitivity of the
      cytological investigation was 67% and respectively 75% of the histological
      investigation. The sensitivity could be raised to 82% in this population by
      combining the two investigations. On the other hand in aneuploid tumors, the
      sensitivity could only be increased from 93% and 88% respectively to 97% by
      combining cytology and fine-needle histology. SUMMARY: Our investigations show
      that the sensitivity of morphological diagnostics can be raised especially in the
      highly differentiated HCC with a physiological DNA content by combination of
      cytological and fine-needle histological investigations.

PMID- 12806544
TI  - [Splenic rupture after ERCP].
AB  - We report on a 52 year old woman, who developed splenic rupture after endoscopic
      sphincterotomy for multiple biliary stones. After hemorrhagic shock had
      developed, the diagnosis was established by computed tomography and ultrasound
      guided paracentesis. The patient was treated by emergency splenectomy. The case
      report stresses the necessity to be aware of splenic rupture as a rare
      complication after ERCP. A review of the current literature regarding splenic
      rupture is provided and mechanisms of splenic trauma and risk factors are
      discussed.

PMID- 12806543
TI  - [Drug- and toxin-induced hepatotoxicity].
AB  - The liver is essential for metabolism of drugs and exogenous toxins. Therefore,
      liver toxicity due to natural, domestic and industrial toxins or drugs is common
      but rarely recognised. Although thorough epidemiological data are missing, the
      number of cases with drug-induced liver toxicity is increasing, parallel to the
      growing number of drugs. Adverse hepatic reactions may present as acute or
      chronic liver damage. Independent from the cause and mechanism of liver damage,
      the clinical presentation may be either cytolytic or cholestatic. In addition,
      liver damage may be accompanied by a systemic hypersensitivity reaction against
      the applied agent. Drug- or toxin-induced liver damage includes vascular damage,
      induction of liver tumours and development of liver cirrhosis. The prerequisite
      for specialised treatment of drug-induced adverse hepatic reactions is
      establishing the diagnosis which is obtained by a thorough medical history taken
      by an experienced physician with a special emphasis on drug or toxin exposure.
      The diagnosis may be confirmed by additional diagnostic measures (e. g. liver
      biopsy) or the clinical course after exposure to the causing agent has been
      stopped. Only in a minority of cases a definite treatment may be available.
      Therefore, the main aim is to prevent chronic liver damage through early and
      correct diagnosis. Due to the extensive variety of possibly liver toxic drugs and
      chemical agents this aspect is a major challenge to physicians.

PMID- 12806545
TI  - [Percutaneous transhepatic retrieval of an intraoperatively displaced biliary
      stent].
AB  - Biliary stents play an important role in the treatment of jaundice due to
      malignant and/or benign diseases of the bile duct. Biliary stents are primarily
      introduced endoscopically whereas the percutaneous transhepatic technique is
      employed after endoscopic failure. Proximal and distal displacement or migration
      is a rare complication, but there is a risk of considerable morbidity and
      mortality, so that the extraction of the prosthesis is recommended in these
      cases. Again, endoscopic removal is the approach of choice. For stent retrieval
      multiple techniques have been described, including Dormia basket, special
      forceps, Fogarty balloon catheter, ball tip catheter and loop catheter.
      Endoscopic recovery often uses a combination of these techniques reaching a
      success rate of 90%. However, in patients following hepaticojejunostomy or
      Bilroth II procedure an endoscopic retrieval cannot be performed for obvious
      technical reasons. Consequently, percutaneous transhepatic stent removal must be
      considered. Ensuring a correct technique transhepatic removal is equally
      successful and safe, thus eliminating the risks of a surgical procedure.

PMID- 12806546
TI  - [Recurrent intestinal bleeding in a patient with arterio-venous fistulas in the
      small bowel, limited mesenteric varicosis without portal hypertension and
      malrotation type I].
AB  - A case of vascular malformations of the small intestine associated with
      malrotation Type I of the right colon is reported. Representing rare conditions,
      vascular malformations in the small bowel are not accessible endoscopically.
      Therefore, gastrointestinal haemorrhage originating from this "terra incognita"
      is difficult to diagnose. Our patient had a medical history of anaemia of 17
      years before admitted to our hospital. After a preoperative blood pool scan had
      evidenced the bleeding source in the proximal jejunum, the patient underwent
      explorative laparotomy. The bleeding source was identified and resection of a
      jejunal segment was performed. Intraoperatively, malrotation type I was found.
      Histological examination revealed angiodysplasia extending full thickness of the
      intestinal wall with predominance in the submucosa and serosa. Secondary
      arterialisation was seen in the vessels of the serosa resembling varicosis-like
      lesions at gross inspection. The patient did not suffer from portal hypertension.
      Postoperative course was uneventful and no further bleeding occurred.

PMID- 12806549
TI  - [Pathophysiology and therapy of pruritus in cholestatic liver diseases].

PMID- 12806554
TI  - Guides to an efficient search for the best evidence.
AB  - As a clinician, the selection of the best treatment options for a patient given
      her clinical diagnosis can be challenging. Textbooks and the knowledge base
      acquired during residency and fellowship training may be out of date. The
      following article outlines how to perform a literature search to survey the
      available treatment options and ultimately how to look for evidence-based
      guidelines for management of the clinical problem.

PMID- 12806555
TI  - Evidence-based medicine for diagnostic questions.
AB  - When searching the medical care literature for evidence on a diagnostic test,
      three questions should be addressed each time a study is found: (1) Is this
      evidence about a diagnostic test valid? (2) Does the test accurately discriminate
      between patients who do and patients who do not have a specific disorder? (3) Can
      the test be applied to this patient who is right now sitting in front of me? We
      will discuss hysterosalpingography (HSG) as an example of a valid and accurate
      diagnostic test to be applied in a general population of subfertile couples to
      assess tubal patency (specificity 0.83). HSG is an unreliable test for diagnosing
      tubal occlusion however (sensitivity 0.65). If HSG were normal, other
      investigations could be pursued and diagnostic laparoscopy (LS) only performed if
      conception had not occurred by a later date. If HSG were abnormal, LS would be
      needed to confirm or exclude tubal occlusion. Patients with risk factors for
      pelvic or tubal disease, including an abnormal Chlamydia antibody test (CAT) and
      those showing abnormalities at pelvic examination, should proceed directly to LS
      because they are significantly more likely to have pelvic pathology. A completely
      different issue would be HSG as a prognostic test for the occurrence of
      pregnancy. In theory, the occurrence of pregnancy may be considered a gold
      standard; however, in reproductive medicine, with so many causes of subfertility
      other than tubal pathology, a diagnostic test for one single disorder, if normal,
      will never be able to accurately predict the eventual occurrence of pregnancy.

PMID- 12806556
TI  - Characteristics of good diagnostic studies.
AB  - Whether or not patients are better off from undergoing a diagnostic test will
      depend on how test information is used to guide subsequent decisions on starting,
      stopping, or modifying treatment. Consequently, the practical value of a
      diagnostic test can only be assessed by taking into account subsequent health
      outcomes. In the appraisal of diagnostic test studies, it is essential to
      discriminate between studies that report on the accuracy of a diagnostic test and
      studies that report on health outcomes of strategies that incorporate diagnostic
      tests. In a study that reports on diagnostic accuracy, a cohort of patients is
      subjected to at least two diagnostic tests: the index test and the reference
      test, the latter usually being the best method available to detect the target
      condition. The accuracy of the index test can be expressed in terms of
      sensitivity, specificity, or likelihood ratios. Studies that compare two or more
      strategies that incorporate diagnostic tests as well as therapeutic interventions
      should be approached differently. Such studies do not require expression of test
      accuracy in terms of sensitivity and specificity. The merit of diagnostic tests
      evaluated in such studies can be expressed by comparing relevant outcomes of both
      strategies. The effectiveness of such strategies can be compared similarly as the
      effectiveness of treatment. However, due to the fact that the effect of a
      diagnostic test on health outcome is not as direct as the effect of treatment on
      health outcome, the design of outcome studies reporting on diagnostic tests
      requires special attention. It is important to establish a clear link between the
      result of the test under study and subsequent therapeutic management.
      Furthermore, trial efficiency can be improved by moving the point of
      randomization from the decision point, whether or not to test, to the point where
      a decision has to be made regarding what to do with the positive test results.

PMID- 12806557
TI  - Evaluating the medical literature in reproductive medicine: questions concerning
      prognosis.
AB  - To illustrate the recommended approach to questions concerning prognosis and the
      formulation of clinical recommendations, the principles of evidence-based
      medicine were applied to questions regarding the cardiovascular health risks
      associated with polycystic ovary syndrome (PCOS) and the effects of treatment on
      risk. A critical examination of the published literature reveals that the
      clinical diagnosis of PCOS does not, by itself, increase the risk of developing
      coronary heart disease (CHD) or adversely affect the prognosis in women with CHD.
      Rather, any increased risks can be attributed to other known risk factors
      (obesity, hypertension, diabetes, dyslipidemia) commonly observed in women with
      the disorder. Treatment strategies that decrease the probability of developing
      such co-morbid conditions (diet, exercise) or are effective in their management
      (antihypertensives, statins, insulin-sinsitizing agents) may be expected to
      reduce risk or improve prognosis, but available evidence is insufficient to
      warrant a general recommendation for metformin treatment as a CHD risk reduction
      strategy in all women with PCOS.

PMID- 12806558
TI  - Characteristics of the best prognostic evidence: an example on prediction of
      outcome after clomiphene citrate induction of ovulation in normogonadotropic
      oligoamenorrheic infertility.
AB  - The standard first-line treatment for normogonadotropic anovulatory infertile
      patients [referred to as World Health Organization group 2 (WHO 2)] is ovulation
      induction using clomiphene citrate (CC) in incremental doses. Twenty to 25% of
      women show clomiphene-resistant anovulation (CRA), that is, they remain
      anovulatory even after multiple attempts with increased doses of CC. About 50% of
      the ovulatory CC patients conceive within six CC-induced cycles. Given the
      heterogeneous nature of the group, the individual prognosis (i.e., the chance of
      success) will vary considerably between patients. In the event an individual
      prognosis of each patient would be available before the start of the treatment,
      the overall efficiency of ovulation induction could be improved. Prognostic
      evidence at an individual level should use multiple patient variables, including
      results from previous treatments (if any). When variables are interdependent, a
      statistical model can be used to relate individual characteristics with the
      predicted outcome. Such a model will provide estimates of prognosis for
      individualized patient profiles, allowing new patients to profit from the
      experience of the cohort of previous patients used to build the model. This paper
      discusses the prediction of time to pregnancy following induction of ovulation
      with CC. This prediction was broken down in two steps, leading to two separate
      prognostic models. The first model predicts an intermediate outcome, the chance
      that the patient will be CRA (i.e., no ovulation in response to CC medication);
      the second model predicts the final outcome (time until pregnancy) in women who
      do ovulate. The CRA model was based on a prospective cohort study of 201 patients
      with normogonadotropic oligoamenorrheic infertility, 45 of whom were CRA (22%).
      It contained four predictor variables all related to the diagnosis of PCOS within
      the group of WHO 2: Increased free androgen index (FAI; hyperandrogenemia),
      elevated body mass index (BMI; obesity), greater mean ovarian volume (as an
      ultrasound feature of polycystic ovaries), and amenorrhea were all predictive for
      CRA. The second model was based on the non-CRA patients and contained two
      prognostic variables: increased age and oligomenorrhea were predictive for longer
      time to pregnancy after first ovulation with CC. Using the example of the
      prediction of time to pregnancy following induction of ovulation with CC, we
      present and discuss characteristics of good prognostic evidence for clinical use,
      focusing on study design, statistical analysis, evaluation, and presentation of
      results.

PMID- 12806559
TI  - Evidence-based medicine for treatment: an in vitro fertilization trial.
AB  - Evidence-based evaluation of treatment is a pivotal component of an effective and
      satisfying clinical practice. When the best evidence has been identified, it can
      be efficiently assessed on three levels: Are the methods valid? Is the effect
      sufficiently large to be meaningful to patients? Are the patients,
      intervention(s), and outcomes studied applicable to our own patients? These
      criteria were applied to a multicenter trial that evaluated whether
      intracytoplasmic sperm injection (ICSI) was superior to in vitro fertilization
      (IVF) among infertile couples with no known male factor who were on a waiting
      list for IVF. The study was a well-designed randomized controlled trial that
      effectively concealed the randomization list and took reasonable steps to exclude
      bias. The results seemed important because the number needed to treat (13) was
      relatively low and significant, but the primary outcome (implantation rate) was
      not clinically meaningful. The trial results would have been relevant to most
      infertile couples with no known male factor if it had been powered to evaluate a
      difference in a more relevant clinical outcome, such as live birth. Thus, it has
      not been shown definitively that ICSI is inferior to IVF among couples with no
      known male factor, and clinical demand for ICSI may continue to rise.

PMID- 12806560
TI  - Randomized clinical trials: the meeting place of medical practice and clinical
      research.
AB  - Randomized clinical trials (RCTs) have been used to assess interventions
      affecting health since biblical times. They provide the most valid means of
      measuring the true effects of intervention compared with no treatment or placebo.
      Although they can also be used to assess the value of diagnostic tests, this
      article focuses on randomized trials in the context of treatment. Key elements of
      an RCT include: the explicit definition of a clinically relevant question; the
      identification of an appropriate sample of patients; a clearly defined and
      reproducible intervention; an appropriate intervention and comparator; clinically
      relevant, measurable outcomes; and appropriate tools for measurement and
      analysis. It is also essential to establish that the question posed is ethical,
      the methods of study are valid, and that follow-up is complete, with an "intent
      to treat" analysis. Results are best presented using both proportions and
      absolute numbers. By providing clinical decision-makers with numbers needed to
      treat or harm, decisions may be better informed and easier to understand, than if
      proportions alone are used.

PMID- 12806561
TI  - Ovarian cancer and fertility medications: a critical appraisal.
AB  - Ovarian cancer is the fifth most common cancer in the Western world. Infertility
      and nulliparity are independent risk factors for this disease. The possible link
      between fertility drugs and ovarian cancer remains controversial. Despite concern
      regarding increasing use of fertility therapy, the incidence of ovarian cancer in
      the Western world has remained stable for several decades. Evaluation of the
      literature requires assessment of the validity, importance, and applicability of
      the study to your particular patient. The following article demonstrates how to
      conduct such an assessment. The data to date do not support a causal relationship
      between fertility drugs and ovarian cancer. In fact, infertility therapy may
      confer protection for those patients who conceive. Further prospective, long-term
      data are needed to further delineate this relationship.

PMID- 12806562
TI  - Characteristics of good causation studies.
AB  - The study of causal relationships is important when addressing questions of
      efficacy of treatment interventions and etiology of disease. The evaluation of a
      cause-and-effect relationship between exposure to a putative causal factor and
      outcome can be undertaken using a variety of study designs including randomized
      controlled trial and cohort and case control studies. Study participants should
      be selected in a manner that minimizes bias and confounding and is representative
      of the target population. Confounding can be controlled by using several
      strategies including restriction, randomization, stratification, matching, and
      multivariable analyses. The degree of association is then summarized by the
      relative risk for prospective studies and the odds ratio for retrospective
      studies. The precision of these estimates should be indicated by providing their
      confidence intervals. Important indicators of causation are correct temporal and
      dose-response relationships between exposure and outcome, a large magnitude in
      the strength of association, and consistency and specificity of association.
      Biological and epidemiological sensibility and analogy to other well-established
      relationships provide additional support for a causal hypothesis.

PMID- 12806563
TI  - Evaluating economic studies in reproductive medicine.
AB  - Healthcare professionals are under increasing pressure to stem the rise of
      healthcare costs and national healthcare expenditures. This has led to great
      interest in cost-effective therapy for patients. This article reviews the
      different types of economic analysis of medical practice and the components of a
      cost-effective analysis. It also reviews how to evaluate a cost-effectiveness
      paper and apply it to clinical practice. Economic analysis of a medical practice
      is a formal and quantitative method of comparing alternative strategies with
      respect to cost and outcomes. These analyses are frequently poorly performed,
      limiting their applicability to clinic practice. After reading this review, a
      physician should be better equipped to effectively evaluate economic analyses.

PMID- 12806564
TI  - Evaluating systematic reviews and meta-analyses.
AB  - Systematic review and meta-analysis procedures make use of explicit methods to
      methodically search and critically appraise and synthesize the medical care
      research literature. The methods involve refining a clinical question, designing
      a search procedure to find eligible studies, and determining the validity of the
      eligible studies. Independent data extraction by two or more reviewers is
      preferred. Agreement between the reviewers with respect to relevance and validity
      should be measured. Meta-analysis procedures estimate an overall average effect
      from the individual study effects and determine whether these effects appear to
      measure the same relationship (that is, the studies are not heterogeneous). In
      the inverse variance method, which is most frequently applied, the overall effect
      is a weighted average of the individual study effects, where each weight is the
      inverse of the study variance. To evaluate a systematic review, first determine
      whether it addresses a question that is relevant to the patients, treatments, and
      outcomes that are usual in your clinical practice. Then assess the validity of
      the systematic review, which is reflected by quality of the individual studies,
      the rigor with which the systematic methods were applied, and the extent of
      heterogeneity. If the results of the systematic review are valid, then is the
      effect important enough to make a difference in your clinical practice? Applying
      the results to an individual patient involves the absolute treatment effect or
      the number needed to treat, and an awareness of the patient's specific level of
      risk and personal preferences.

PMID- 12806565
TI  - Effect of piracetam on cognitive performance in patients undergoing bypass
      surgery.
AB  - In this study, the protective effect of piracetam on select aspects of cognitive
      function in patients undergoing bypass surgery was investigated. Male patients (n
      = 64) with an indication for a surgical revascularization using artificial
      extracorporal circuits were randomly assigned in a double-blind fashion to
      receive a single challenge of 12-g piracetam infusion or placebo (sterile saline)
      prior to the bypass surgery. A brief battery of neuropsychological tests for
      verbal and non-verbal short-term memory and attention was administered 1 day
      before and 3 days after the surgical intervention. There was a significant
      difference in short-term memory and attention, with the piracetam-treated
      patients producing a better level of performance 3 days after surgery compared to
      the placebo group. The overall postoperative cognitive function (z-transformation
      of all 6 test results) was more significantly (p < 0.001) reduced in the placebo
      group than in the piracetam group (z = -1.19 +/- 0.72 vs. -0.46 +/- 0.58,
      respectively). A single challenge of 12-g piracetam infusion prior to surgical
      intervention might offer a short-term neuroprotective effect for patients
      undergoing cardiac bypass surgery. Whether this effect persists for a longer
      period of time requires further investigation.

PMID- 12806566
TI  - Etomidate vs. thiopentone in electroconvulsive therapy. An interdisciplinary
      challenge for anesthesiology and psychiatry.
AB  - The choice of anesthetic for electroconvulsive therapy is based on the anesthetic
      requirements to be met and on the agent's impact on the seizure threshold. Thus,
      the non-barbiturate anesthesia etomidate revealed properties to enhance the
      seizure duration. Even though precisely this feature makes etomidate so valuable,
      little research has been done on the use of etomidate in ECT. The aim of the
      present study was to compare the barbiturate anesthesia thiopentone with
      etomidate, with the focus of attention being the quality of seizure. In 13
      patients, the paradigm of a single intra-individual crossover anesthesia during
      maintenance ECT was selected. The excitatory effects and the
      electroencephalographic changes were described. Furthermore, significant
      differences in motor seizure duration (26.69 sec +/- 9.7 vs. 35.92 sec +/- 9.2; p
      < 0.007) and EEG seizure duration (39 sec +/- 14.1 sec vs. 61 sec +/- 22.2 sec; p
      < 0.0009) were observed. Our results confirm previous findings and reveal that
      after etomidate the quality of seizure can be improved not only in terms of
      duration. The growing knowledge of the mode of action of anesthetics/hypnotics
      from an anesthesiological point of view and the better understanding of
      subcortical and cortical mechanisms, with particular consideration of the motor
      seizure threshold, facilitate a differentiated choice of the narcotic and the
      optimization of short anesthesia in the course of electroconvulsive therapy.

PMID- 12806567
TI  - Therapeutic drug monitoring of tricyclic antidepressants: how does it work under
      clinical conditions?
AB  - Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is
      established in the treatment of depression to optimize outcome and safety.
      However, there are few reports on TDM under naturalistic clinical conditions. In
      the present study, we investigated a TDM group (TDM) and a randomly assigned
      parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were
      analyzed in both cohorts, but feedback and dose recommendation were only provided
      for the TDM group. Serum levels of TCA were assessed by high-performance liquid
      chromatography (HPLC). The outcome was measured weekly using the Hamilton
      Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and
      the UKU side-effect scale. 84 patients with depressive disorder according to DSM
      IV were recruited in three centers (TDM, n = 43; no-TDM, n = 41; mean age 49.9 +/
      13.2 years, 63.1 % female). Patients were treated with either amitriptyline (n =
      69) or doxepin (n = 15); the mean dosage at endpoint was 126 +/- 35 mg and 155 +/
      47 mg, respectively. The mean study duration was 21 +/- 8 days. Both groups
      improved according to HAMD (from 25.2 +/- 8.4 at baseline to 12.0 +/- 7.4 at
      endpoint) and CGI scores (68 % responders). Moderately severe or severe side
      effects occurred in 16 % of patients. Adequate dose adjustment was significantly
      higher in the TDM group (60 % vs. 46 %, p < 0.05); this led to a significantly
      higher rate of therapeutic serum levels in the TDM group (58 % vs. 44 %, p <
      0.05). Direct effects of TDM were not found for effectiveness. Therapeutic TCA
      serum levels over weeks one to three, however, were associated with significantly
      better outcome at endpoint (p < 0.05) as measured with changes in the HAMD or CGI
      response rates from baseline to endpoint. Finally, considerable side effects
      occurred significantly more often when serum levels were above the therapeutic
      range (27 % vs. 11 %; p < 0.01). We conclude that treating depression with TCA
      can be optimized by early TDM, which is superior to clinical judgment on its own.
      Since the psychiatrists in charge were less than completely "compliant" to the
      recommendations provided together with serum levels, the effect could be more
      pronounced than this study shows. The results encourage further studies in order
      to optimize antidepressant pharmacotherapy when using TDM appropriately.

PMID- 12806568
TI  - Schizophrenic patients' subjective reasons for compliance and noncompliance with
      neuroleptic treatment.
AB  - Although several factors influencing schizophrenic patients' compliance with
      neuroleptic treatment have been investigated, the subjective reasons that
      patients are willing or reluctant to take medication have rarely been examined.
      In a follow-up study of a sample of schizophrenic patients currently undergoing
      psychiatric treatment in the city of Leipzig, 307 patients were asked about their
      subjective reasons for medication compliance or noncompliance by administering
      the Rating of Medication Influences (ROMI) Scale. The perceived benefit from
      medication proved to be the main reason for patients' compliance with neuroleptic
      treatment. Respectively, patient-reported noncompliance was mainly explained by
      negative side effects of medication. However, there were no statistically
      significant differences in responses between the patients receiving conventional
      versus second-generation antipsychotics. A positive relationship with the
      therapist and a positive attitude of significant others toward neuroleptic
      treatment contributed to patients' medication compliance. Reasons for
      noncompliance with neuroleptic treatment were lack of acceptance of the necessity
      of pharmacological treatment and lack of insight into the disease. The results
      emphasize the importance of psychoeducation in enhancing patient compliance with
      neuroleptic treatment.

PMID- 12806569
TI  - The lateral spread of epileptiform discharges in rat neocortical slices: effect
      of focal phencyclidine application.
AB  - In vitro and in vivo brain slice techniques were used to examine phencyclidine
      (PCP) effects on the lateral propagation of epileptiform field potentials (EFP)
      across adjacent areas of rat frontal neocortex. Epileptiform activity was induced
      by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous
      field potential recordings of EFP were obtained from four microelectrodes placed
      2-3 mm apart across coronal slices in the third layer. PCP, applied focally
      between recording sites, blocked rapid propagation across treated areas and
      resulted in the emergence of spatially separate, independent pacemakers. The
      characteristics of paroxysmal depolarization shifts did not change significantly
      by the blockade of lateral propagation of EFP. The same asynchronized pattern of
      EFP conduction was observed after local application of the N-methyl-D-aspartate
      (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local
      administration of haloperidol as well as NMDA before PCP application reversibly
      prevented appearance of multiple pacemakers. Focal application of dopamine
      produced an abnormal pattern of lateral conduction of EFP in 50 % of tested
      slices. Pacemaker failure as an indicator of functional impairment of cortical
      integration is the proposed mechanism for developing of schizophrenia-like
      psychosis associated with epilepsy. Abbreviations. APV: DL-2-amino-5-phosphono
      valeric acid EEG:electroencephalogram EFP:epileptiform field potentials NMDA:N
      methyl-D-aspartate PCP:phencyclidine SLPE:Schizophrenialike psychosis associated
      with epilepsy

PMID- 12806570
TI  - Omeprazole reduces clozapine plasma concentrations. A case report.
AB  - A number of interactions of the atypical antipsychotic clozapine with other drugs
      are well known, some of which can be attributed in part to the pharmacokinetic
      interactions associated with cytochrome P450 enzymes during drug metabolism.
      Clozapine is mainly metabolized by the cytochrome P450 isoenzyme 1A2. The proton
      pump inhibitor omeprazole can induce CYP1A2. We report on two patients with
      schizoaffective disorder who received omeprazole in addition to clozapine because
      of gastrointestinal complaints. Before the co-medication with omeprazole was
      started, the patients had been receiving clozapine for 78 and 41 days and for 40
      and 8 days at a stable daily dose of 325 mg (patients 1 and 2, respectively). The
      co-medication with omeprazole was associated with a reduction in the plasma
      levels of clozapine of 41.9 % and 44.7 %, respectively, in these patients. The
      decrease in the plasma concentrations of clozapine in the presence of omeprazole
      might be due to the induction of the cytochrome P450 isoenzyme CYP1A2. If
      patients are receiving omeprazole as co-medication, close monitoring of plasma
      clozapine levels is recommended. If clozapine levels drop, the drug should be
      adjusted accordingly. If necessary, an alternative to omeprazole should be
      chosen.

PMID- 12806571
TI  - Panic attacks, spike-wave activity, and limbic dysfunction. A case report.
AB  - INTRODUCTION: Several lines of evidence indicate that an increased neuronal
      excitability of the corpus amygdaloideum and hippocampus may be one
      pathophysiological condition of panic attacks. METHODS: In this report, we will
      describe the case of a 54-year-old female patient with a depressive syndrome who
      first experienced very rapid atypical panic attacks with dizziness, trance-like
      and distorted optical perception, but without clear epileptic symptoms. RESULTS:
      Several EEG recordings showed temporal sharp-waves and spike-wave patterns.
      Magnetic resonance imaging (MRI) revealed a hypodense area near left mesial
      temporal structures. Brain imaging with SPECT showed a hypoperfusion of the basal
      temporal cortical structures on the left side. Treatment with antidepressants had
      no effect, but the addition of valproic acid led to an attenuation of the panic
      attacks and epileptic potentials on the EEG. DISCUSSION: A clinical trial using
      anti-epileptics could be successful in patients not responding to antidepressants
      or in the presence of epileptiform EEG activity. In this article, we will review
      the literature concerning the complex relationship between panic attacks and
      ictal activity of limbic structures and discuss the difficult diagnostic
      classification of atypical cases.

PMID- 12806572
TI  - Tongue reconstruction with free radial forearm flap after hemiglossectomy: a
      functional assessment.
AB  - Thirty-three patients with squamous cell carcinoma of the anteriolateral part of
      the tongue underwent a 50 percent resection of the tongue. The surgical defect
      was reconstructed with a microvascular radial forearm flap. All the flaps were
      especially designed to have a narrow waist, shaped like an omega in cross
      section, thus allowing for a free tongue tip, and avoiding suturing the edge of
      the flap to the soft palate and tongue base. Sixteen patients were evaluated for
      swallowing and speech function at least 6 months following reconstruction. With
      this technique, the majority of the patients had nearly normal deglutition,
      although their speech was still unsatisfactory. However, the speech function in
      this series was better than that in other reported series.

PMID- 12806573
TI  - True aneurysm of the radial artery after iatrogenic injury and successful
      reconstruction with an interposition vein graft.
AB  - Aneurysm of the radial artery is rare and is usually seen after penetrating
      traumas. The radial artery is most affected at the distal part where it lies
      superficially. Iatrogenic injuries, such as catheter placement and arterial blood
      collection, are important interventions in hospitalized patients. In this paper,
      the authors present a case with a distal radial artery true aneurysm after
      prolonged radial artery catheterization. Although treatment of aneurysm of the
      radial artery is still controversial, they reconstructed the excised segment with
      an interposition vein graft, and recommend such vessel repair to maintain patency
      whenever possible.

PMID- 12806574
TI  - Use of the free fibula flap for restoration of orbital support and midfacial
      projection following maxillectomy.
AB  - A total maxillectomy defect, if left unreconstructed or if poorly reconstructed,
      can lead to enophthalmos, orbital dystopia, feeding and speech problems, and loss
      of midfacial projection and vertical facial height. When the eye is preserved,
      despite resection of the supporting infraorbital bone during maxillectomy, bone
      reconstruction needs to be considered, using a vascularized bone flap. The
      authors have used the free fibula flap to simultaneously provide orbital support
      and restore midfacial projection in three patients, following total maxillectomy
      without orbital exenteration. For large maxillectomy defects with insufficient
      bony support, a free fibula flap should be considered as a reconstructive method,
      to adequately restore contour and the necessary structural support, and to
      provide optimal aesthetic and functional results.

PMID- 12806575
TI  - Reconstruction of the replanted hand with latissimus dorsi muscle and serratus
      anterior fascia combined flap.
AB  - Reconstruction with the latissimus dorsi muscle flap, combined with the serratus
      anterior fascia flap, was performed to cover two large and separate palmar and
      dorsal forearm skin defects in a patient, whose hand had been replanted 20 days
      earlier after traumatic amputation at the distal forearm level. As a result, a
      total forearm amputation was salvaged by microsurgical replantation and a free
      combined flap of the subscapular system. This new application of the combined
      flap allowed the reconstruction of large and separate wounds of the replanted
      hand, and provided gliding surfaces for tendons.

PMID- 12806576
TI  - Vasculature of the peroneal artery: an anatomic study focused on the perforator
      vessels.
AB  - Based on the dissection of 20 fresh cadaver legs, the authors have further
      defined the vascular anatomy of the peroneal artery and its cutaneous perforator
      vessels. They identified a total of 95 cutaneous perforators of the peroneal
      artery greater then 0.3 mm in 20 legs. The average number of cutaneous
      perforators was 4.8 (range: three to seven) per leg. The cutaneous perforators
      were either musculocutaneous (34 percent) or septocutaneous (66 percent). The
      musculocutaneous perforators were found predominantly in the upper two-thirds of
      the lower leg; the septocutaneous perforators were located in the lower two
      thirds of the leg. The external diameter of the cutaneous perforators at the
      posterior border of the fibula was 0.6 (range: 0.3 to 1.5) mm. The blood supply
      of the proximal fibula epiphysis and fibula head was found not to be in the
      vascular territory of the peroneal artery. These results are the basis of the
      established osteoseptocutaneous fibula transfer, the peroneal fasciocutaneous
      free flap, and the double-paddle peroneal tissue transfer that all require
      dissection of highly vascularized tissue adjacent to the fibula, in order to
      reach the peroneal vessels. These constant anatomic findings should encourage the
      surgeon to harvest skin flaps just to the level of the posterior border of the
      fibula, thereby creating perforator flaps based on the peroneal system.

PMID- 12806577
TI  - Treatment of post-traumatic tibial osteomyelitis using microsurgical flaps.
AB  - Between 1994 and 1998, the authors treated 70 patients presenting with post
      traumatic tibial osteomyelitis. Eighty-five percent were males, with a mean
      patient age of 32 years. The mean duration of the disease was 2 years. Fifty-one
      percent were of type IV in the Cierny-Mader classification. The mean follow-up
      period was 36 months. Case management was through thorough debridement,
      antibiotic therapy, and soft-tissue reconstruction using free flaps: latissimus
      dorsi (39.4 percent), scapular (28.2 percent), lateral arm (19.7 percent), and
      anterior serratus (12.7 percent). To evaluate the results, the control of
      infection and the quality of the soft tissue repaired were considered. The
      success rate was 90 percent. The authors conclude that their described method
      constitutes an effective treatment for post-traumatic tibial osteomyelitis.

PMID- 12806578
TI  - Clinical case experience using microsurgical venous flaps for soft-tissue
      coverage of the lower extremity.
AB  - Numerous venous flap models have been experimentally introduced and clinically
      attempted in reconstruction of soft-tissue defects. The authors report experience
      in soft-tissue coverage with microsurgical saphenous venous flap transfers in
      five patients with lower-extremity wounds. Four of these flaps failed
      postoperatively. Unhealthy recipient beds and inflamed veins were potential
      causes for these flap failures. Easy dissection without sacrifice of the artery
      would seem to provide an ideal situation for venous flap utilization, but this
      rate of failure prohibits recommendation of this flap in large, traumatic wounds.

PMID- 12806579
TI  - Biologic activity of nerve growth factor slowly released from microspheres.
AB  - Efficient and sustained delivery of neurotrophic factors to the regenerating
      nerve in biologically active form presents a challenge. Protein delivery in
      biodegradable microsphere vehicles has been difficult, based on destabilization
      and breakdown during both the loading and release phases. This study examines the
      extravasation and stability of Nerve Growth Factor (NGF) in polylactic-co
      glycolic acid (PLGA) microspheres, via both ELISA and PC-12 bioassays. PLGA
      microspheres co-loaded with bovine serum albumin (BSA) and NGF were prepared by a
      water-in-oil-in-water (W/O/W) technique, using chloroform for the organic phase
      and 1 percent polyvinyl alcohol (PVA) for the emulsion step. Aliquots of
      lyophilized microspheres were incubated in double distilled water (dd H2O) at 37
      degrees C, and the supernatants assayed over time for NGF activity. ELISA was
      utilized for quantitative determination of NGF concentration, and a PC-12 cell
      neurite outgrowth assay assessed biologic activity. Both ELISA and PC-12 assays
      demonstrated the extravasation of NGF from microspheres. Over time, the predicted
      concentration of NGF via the two assays differed, suggesting possible
      preservation of recognizable epitopes for ELISA, but loss of biologic activity.
      NGF can be stored and released from microspheres. Extravasation studies should
      include biologically relevant assays for activity.

PMID- 12806581
TI  - Examining microcirculation improves the angiosome theory in explaining the delay
      phenomenon in a rabbit model.
AB  - Topographic and temporal changes in circulation were studied with laser Doppler
      flowmetry in rabbit dorsal skin flaps comprised of three vascular territories.
      The reduced caliber vessels along the dorsal median line, rather than the vessels
      interconnecting the thoracodorsal and deep circumflex iliac vascular trees,
      behaved as true choke vessels. The authors found an increased proximal
      circulation lasting for 48 to 72 hr. This coincided with the reported rapid phase
      of choke vessel dilatation. The increase in distal circulation began after
      postoperative day 3, coinciding with the resolution of proximal hyperemia but not
      with the earlier prominent vasodilatation. Secondary elevation of the flaps at 3
      weeks did not disturb the homogeneous distribution of circulation and did not
      cause a hyperemic response at postoperative 24 hr. Based on these findings, the
      authors postulate that the same mechanisms may underlie the rapid choke vessel
      dilatation and microvascular dilatation observed at 48 to 72 hr postoperatively.
      Surgical delay may work not only by diminishing the resistance to blood flow
      along the flap, but also by diminishing the steal effect of increased proximal
      microcirculation, which characterizes this period, over the distal circulation.

PMID- 12806582
TI  - Prelaminated fasciomucosal flap using tongue mucosa in a rat model.
AB  - Reconstruction of tongue defects from various causes has been a continuing
      challenge to reconstructive surgeons. If tongue mucosa is used in tongue
      reconstruction, some disadvantages of cutaneous flaps can be overcome, and also
      some functions of the tongue, like handling, compressing, and macerating of food,
      can be improved. The purpose of this study was to assess the feasibility of a
      prelaminated fasciomucosal flap, using rat tongue mucosa. The survival rate of
      prelamination and revascularization of the dorsal tongue mucosa graft was
      evaluated. Changes in the epithelial cell layer and tongue papilla over time were
      observed. Tongue mucosa graft prelamination was feasible in most cases, and the
      survival rate was 83.3 percent. The number of microvessels increased with time,
      and statistically significant positive correlations were observed (Spearman rank
      correlation rs =0.709 p<0.05). The results validated that it is possible to
      fabricate a fasciomucosal flap using tongue mucosa. However, the prelaminated
      flap should be transferred to the recipient site between 10 and 14 days after
      prelamination, to maintain the papillary morphology of the tongue.

PMID- 12806583
TI  - On "Lengthening of replanted or revascularized lower limbs: is length discrepancy
      a contraindication for limb salvage?" (J Reconstr Microsurgery 2002;18:471-480).

PMID- 12806586
TI  - Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and
      cardiovascular disease.
AB  - An elevation in angiotensin II (Ang II) levels is a common occurrence in a
      diverse number of cardiovascular diseases including hypertension,
      hypercholesterolaemia, atherosclerotic coronary artery disease, left ventricular
      hypertrophy (LVH), heart failure and diabetes. An important effect of Ang II is
      activation of the NAD(P)H oxidase, a major source of reactive oxygen species
      (ROS) production by vascular cells. This increase in cellular ROS contributes to
      the pathogenesis of vascular disease by altering endothelial cell function,
      enhancing smooth muscle cell growth and proliferation, stimulating inflammatory
      proteins, including macrophage chemoattractant agents, growth factors and
      cytokines, and modulating matrix remodelling. Studies of genetically-altered mice
      have unequivocally shown that activation of the NAD(P)H oxidase by Ang II
      contributes to hypertension, LVH and atherosclerosis. Furthermore, increasing
      evidence suggest that the NAD(P)H oxidase contributes to human disease,
      suggesting that it is a potential target for future therapeutic intervention.

PMID- 12806587
TI  - Angiotensin II receptor blockers and cardiovascular outcomes: what does the
      future hold?
AB  - The ability of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor blockers (ARBs) to lower blood pressure (BP) is well established. ACE
      inhibitors (ACE-Is) have also been shown to improve the prognosis of a broad
      range of patients at high cardiovascular risk, including those with heart
      failure, post-myocardial infarction (MI), and nephropathy. These benefits suggest
      that interrupting the renin-angiotensin-aldosterone system (RAAS) with ACE-Is has
      a widespread vasculoprotective effect, provided that BP is also adequately
      controlled. Evidence that RAAS blockade by ARBs also improves long-term clinical
      outcomes in patients with cardiovascular disease has started to accumulate, and
      will be tested further during the coming years as a number of large-scale,
      prospective trials are completed. These trials are investigating the long-term
      protective effects of ARBs on morbidity and mortality in patients with
      hypertension, heart failure, diabetes mellitus, acute MI, or established vascular
      disease. The results should establish the extent to which ARBs exhibit the
      vasculoprotective properties demonstrated by ACE-Is in patients at high
      cardiovascular risk. If ARBs are found to provide benefits that are similar to,
      or even greater than ACE-Is, it may have important implications for drug
      selection, given the excellent tolerability of ARBs. Some studies are also
      investigating whether more extensive RAAS blockade using a combination of an ARB
      and an ACE-I will offer even greater protection than either agent alone.

PMID- 12806588
TI  - ACE inhibition or angiotensin receptor blockade: which should we use in diabetic
      patients?
AB  - Blockade of the effects of angiotensin II (Ang II) by using an angiotensin
      converting enzyme (ACE) inhibitor has been proven to be of value in Type 1
      diabetic nephropathy and in non-diabetic renal disease. Evidence in favour of Ang
      II blockade in Type 2 diabetic patients with renal damage is still lacking for
      ACE inhibitors (ACE-Is), while recent data indicate that angiotensin receptor
      blockers (ARBs) could be the drugs of choice in this situation. On the other
      hand, renal damage from the onset of disease is accompanied by a very significant
      increment in global cardiovascular risk. This fact, as well as that of
      simultaneous renal and cardiovascular protection, have to be considered for drug
      selection. In this sense, ACE-Is have been shown to be the drugs of choice when
      secondary cardiovascular prevention is required, while the evidence in primary
      prevention in hypertensive patients has been shown with losartan in the Losartan
      Intervention For Endpoint reduction in hypertension (LIFE) study. All these facts
      led to the conclusion that both ACE-Is and ARBs can be considered when both renal
      and cardiovascular protection are aimed for in Type 2 diabetic patients.

PMID- 12806589
TI  - The renin-angiotensin-aldosterone system and Alzheimer s disease?
AB  - Epidemiological studies from the last decade have begun to produce evidence that
      the perceived joint occurrence of vascular disease and Alzheimer's disease (AD),
      both common elderly disorders more often believed to occur by chance due to their
      high prevalence, may now actually have a more pathological significance. The
      following review discusses some of this evidence and the implications for
      cognitive decline and the development of AD and how a well-known cardiovascular
      risk factor gene, the apolipoprotein E (APOE) gene, plays a significant role in
      the molecular genetics of AD. It also introduces and discusses recent and
      compelling evidence for the involvement of another well-known cardiovascular risk
      factor gene, the angiotensin-converting enzyme (ACE1) gene, in the pathogenesis
      of AD. This role is suggested in terms of recent molecular genetic association
      evidence implicating the ACE1 insertion/deletion (indel) polymorphism, a more
      recent large haplotype study that greatly extends the ACE1 indel evidence and
      incorporates knowledge accrued from previous cardiovascular disease-focused ACE1
      haplotype studies. Finally, this paper discusses very recent biological evidence
      that further supports a role for ACE1 and hypothesises a number of readily
      testable mechanisms by which the ACE1 enzyme and other components of the renin
      angiotensin-aldosterone system may be implicated in increased risk and/or the
      progression of AD.

PMID- 12806590
TI  - Improvement of impaired coronary vasodilator reserve in hypertensive patients by
      low-dose ACE inhibitor/diuretic therapy: a pilot PET study.

PMID- 12806591
TI  - Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients
      with diabetes mellitus: rationale and design.
AB  - BACKGROUND: Blood pressure (BP) reduction is the key to risk reduction of
      cardiovascular disease or renal failure in hypertensive patients with diabetes
      mellitus. Inhibition of the renin-angiotensin system by an angiotensin-converting
      enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) provides
      efficient BP reduction and renal protection in hypertensive diabetes patients.
      But, despite this, the recommended BP levels can be difficult to achieve and dual
      blockade therapy might be a possible way of obtaining efficient BP reduction in
      hypertensive patients with diabetes. Dual blockade treatment is based on a
      principle of obtaining the broadest and most efficient blockade of angiotensin
      II, by using the combination of an ACE-inhibitor and an ARB. METHODS: The
      Candesartan And Lisinopril Microalbuminuria (CALM II) study is a one centre, one
      observer, double-blind, randomised, active-controlled, parallel-group study,
      investigating the efficacy and tolerability of candesartan cilexetil in
      combination with lisinopril, compared with the maximum recommended dose of
      lisinopril in hypertensive patients with diabetes mellitus. The study design
      consists of two treatment arms with either 16 mg candesartan cilexetil or 20 mg
      lisinopril added to concomitant treatment with 20 mg lisinopril. It comprises 80
      patients with a minimum of 35 patients in each group and statistical power of 90%
      to detect a difference in systolic BP reduction of 6.5 mmHg. CONCLUSION: The CALM
      II study aims to investigate the effects of dual blockade on systolic BP,
      albuminuria, left ventricular mass and function, and retinopathy in hypertensive
      patients with diabetes mellitus.

PMID- 12806592
TI  - No involvement of the AT2-receptor in angiotensin II-enhanced sympathetic
      transmission in vitro.
AB  - Angiotensin II (Ang II) enhances sympathetic neurotransmission via AT(1)
      receptors located on sympathetic nerve terminals. We recently demonstrated that
      inhibition of Ang II-mediated facilitation in the pithed rat by irbesartan
      resulted in a U-shaped dose response curve, which was not observed when PD
      123319, at a concentration that selectively blocks the AT(2)-receptor, was co
      administered. Hence, the irbesartan-mediated  upstroke  might be explained by the
      involvement of the AT(2)-receptor after AT(1) blockade with high-dose irbesartan.
      In the present study, we further investigated the possible role of the AT(2)
      receptor in Ang II-mediated facilitation in vitro. We studied the effect of the
      AT(2)-receptor antagonist PD 123319 (10 nM) on Ang II-enhanced sympathetic
      outflow evoked by electrical field stimulation (EFS) in the rat isolated inferior
      vena cava. Additionally, we investigated the effect of the AT(1)-receptor blocker
      irbesartan (0.1 nM 1  M) on the sequelae of Ang II-enhanced, EFS-evoked
      sympathetic nerve traffic in the presence or absence of PD 123319 (10 nM). PD
      123319 did not influence Ang II-enhanced sympathetic outflow. Irbesartan dose
      dependently attenuate Ang II-augmented transmitter release (pIC50 7.99+0.03),
      whereas no U-shaped concentration-response relationship for irbesartan was
      observed. Co-administration of PD 123319 with irbesartan proved unable to
      influence Ang II-mediated facilitation differently compared with irbesartan
      alone. The experimental observations indicate that the AT(2)-receptor is not
      involved in Ang II-mediated enhancement of sympathetic nerve traffic in the
      present in vitro study.

PMID- 12806593
TI  - Involvement of renal ACE activity in proteinuria-associated renal damage in
      untreated and treated adriamycin nephrotic rats.
AB  - Proteinuria is assumed to play a pathogenetic role in progressive renal damage.
      Angiotensin-converting enzyme (ACE) inhibition reduces proteinuria and provides
      renoprotection. This suggests that ACE activity might play a pathogenetic role in
      the development of proteinuria-induced renal structural damage. We investigated
      this hypothesis in untreated and treated established adriamycin nephrosis, a
      model of proteinuria-induced renal damage. In a time-course experiment, the
      development of renal structural damage in untreated adriamycin nephrotic rats was
      paralleled by a significant rise in renal ACE activity. Moreover, on cross
      sectional analysis, a consistent positive correlation between renal, but not
      plasma, ACE activity and proteinuria, focal glomerulosclerosis and interstitial
      injury was present. Notably, these associations were present, not only in the
      untreated condition, but also during intervention with either ACE inhibition or
      AT(1)-receptor antagonism. Interestingly, we found that higher renal ACE activity
      is associated with more severe renal damage for a given amount of proteinuria,
      suggesting that renal ACE activity may be either a permissive or a promoting
      factor in the processes by which proteinuria eventually leads to renal structural
      damage. This relationship was abolished by renin-angiotensin system (RAS)
      blockade, suggesting that RAS-mediated effects are involved in the relationship
      between renal ACE activity and proteinuria-induced renal damage. In conclusion,
      in untreated as well as treated adriamycin nephrotic rats, renal ACE activity is
      closely associated with renal outcome. This association appears to be independent
      of the specific mode of blockade of the RAS. Renal ACE activity is a consistent
      marker of individual differences in proteinuria-associated renal damage: further
      studies are needed to investigate a possible pathogenetic role in renal damage.

PMID- 12806594
TI  - Transforming growth factor-beta 1-mediated collagen gel contraction by cardiac
      fibroblasts.
AB  - OBJECTIVE: Myofibroblasts and transforming growth factor-beta(1) (TGF-beta(1))
      are key elements of cardiac tissue fibrosis development. The aim of this study
      was to determine whether the ability of TGF-beta(1) to affect the contractile
      activity of cardiac fibroblasts depends on their differentiation into
      myofibroblasts. METHODS: Cardiac fibroblasts (from male adult Wistar rats) from
      passage two were cultured to confluency and incubated on a hydrated collagen gel
      with and without TGF-beta(1) (0, 20, 40, 100, 200, 400 or 600 pmol/L) for one,
      two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine
      serum. RESULTS: TGF-beta(1) dose-dependently increased the contraction of
      collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100
      pmol/L TGF-beta(1). TGF-beta(1) also stimulated 3(H)-thymidine incorporation and
      total protein content in cardiac fibroblasts in the collagen gel lattice. TGF
      beta(1) dose-dependently induced an increase in beta-smooth muscle actin, a
      marker of myofibroblasts. The TGF-beta(1)-induced reduction of area of the
      collagen gel was negatively correlated to the TGF-beta(1)-evoked appearance of a
      smooth muscle actin in the collagen gel matrix. CONCLUSION: Our data demonstrate
      that TGF-beta(1) increased the contractile activity of adult rat cardiac
      fibroblasts and their ability to differentiate into myofibroblasts. Because
      contractile activity was correlated with differentiation, the influence of TGF
      beta(1) on cardiac fibroblast-induced collagen gel contraction might depend on
      the promotion of myofibroblast differentiation.

PMID- 12806595
TI  - Effect of angiotensin-converting enzyme inhibition on endothelial function and
      insulin sensitivity in hypertensive patients.
AB  - INTRODUCTION: Evidence suggests an association between insulin resistance,
      hypertension and impaired endothelial function. Studies have shown that insulin
      resistance precedes the development of hypertension. By improving insulin
      sensitivity, it may be possible to improve hypertension and the subsequent damage
      to vessel walls. Some data indicates beneficial effects of angiotensin-converting
      enzyme (ACE) inhibitors on insulin sensitivity and endothelial function. We aimed
      to investigate these effects of ACE inhibition in the same group of patients with
      essential hypertension. MATERIALS AND METHODS: Nine non-smoking, untreated
      hypertensive patients (38.3+9 years, 4/5 male/female) and 12 age-matched healthy
      subjects (35.2+6.7 years, 5/7 male/female) were included in the study.
      Hypertensive patients were given enalapril maleate (5 40 mg/day) for six months.
      The following parameters were studied at baseline and at the end of treatment
      period. Whole body insulin sensitivity was measured by a formula derived from an
      oral glucose tolerance test and named as the insulin sensitivity index (ISI).
      Insulin was measured by chemiluminescence and glucose by a glucose oxidase
      method. Endothelial function was evaluated as flow-mediated dilatation (FMD) of
      the brachial artery by ultrasonography and expressed as a percentage change
      relative to baseline diameter. Endothelial- independent vasodilatation was
      measured after sublingual nitroglycerine. RESULTS: FMD was impaired in the
      hypertensive group compared with healthy subjects (7.3+3.1% vs. 15.3+4.8%,
      p<0.0005), and ISI values were 1.18+0.6 vs. 4.4+0.9 (p<0.0001) respectively. Both
      insulin sensitivity and FMD improved after the treatment period compared with
      baseline values, FMD increased from 7.3+3.1% to 16.0+2.9% (p<0.0005) and ISI from
      1.18+0.6 to 4.2+1.0 (p<0.0001). FMD and ISI showed a significant positive
      correlation (r=0.67, p<0.001) in the hypertensive group. CONCLUSIONS: Patients
      with essential hypertension have impaired endothelial function and decreased
      whole body insulin sensitivity compared with healthy subjects. Treatment for six
      months with enalapril maleate seems to improve both FMD and ISI. This study
      confirms the beneficial effects of ACE inhibition on both endothelial function
      and insulin sensitivity tested in the same group of essential hypertensive
      patients. The mechanism of these favourable effects of ACE inhibition needs to be
      clarified.

PMID- 12806596
TI  - Biphasic effects of angiotensin (1-7) and its interactions with angiotensin II in
      rat aorta.
AB  - Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the
      vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with
      angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium
      dependent relaxation and vasodilating effects in preparations precontracted with
      phenylephrine. Without preconstriction, Ang (1-7) at high doses (10(-6) 10(-5) M)
      produced either a significant inhibition of Ang II-induced vasoconstriction or a
      non-tachyphylactic vasopressor response. While losartan inhibited the
      vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike
      losartan, blockade of AT(2)-receptors with PD 123319 had no effect. Taking into
      account the biphasic effects of angiotensin (1-7), we propose that it is one of
      the active components of the renin-angiotensin system, which is involved as a
      modulator both in the counter-regulatory actions of Ang II and in the self
      regulation of its own vasodilating effects.

PMID- 12806600
TI  - Novel coronavirus associated with SARS outbreak.

PMID- 12806602
TI  - Approval of Enteryx for GERD recommended by FDA panel.

PMID- 12806603
TI  - Evidence-based medicine: clinical judgment is required.

PMID- 12806604
TI  - Image of the month: pseudomyxoma peritonei.

PMID- 12806605
TI  - Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease
      relatives?
AB  - BACKGROUND & AIMS: One approach to unraveling the genetics of complex inherited
      disease, such as Crohn's disease, is to search for subclinical disease markers
      among unaffected family members. We assessed the possible presence, prevalence,
      and inheritance pattern of subclinical intestinal inflammation in apparently
      healthy relatives of patients with Crohn's disease. METHODS: A total of 49
      patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first
      degree relatives underwent a test for intestinal inflammation (fecal calprotectin
      concentration). The mode of inheritance was assessed from 36 index patients (by
      variance component analysis) when more than 50% of relatives were studied.
      RESULTS: Fecal calprotectin concentrations in patients with Crohn's disease (47
      mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14
      mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L),
      whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal
      calprotectin concentration was increased in 49% of all relatives studied. The
      increased fecal calprotectin concentration among the relatives of the 36 index
      patients had an inheritance pattern that was most consistent with an additive
      inheritance pattern. CONCLUSIONS: There is a high prevalence of subclinical
      intestinal inflammation in first-degree relatives of patients with Crohn's
      disease that conforms best to an additive inheritance pattern. The genetic basis
      for this abnormality may represent a risk factor for Crohn's disease.

PMID- 12806606
TI  - Sex-related differences in IBS patients: central processing of visceral stimuli.
AB  - BACKGROUND & AIMS: Women have a higher prevalence of irritable bowel syndrome
      (IBS) and possible differences in response to treatment, suggesting sex-related
      differences in underlying pathophysiology. The aim of this study was to determine
      possible sex-related differences in brain responses to a visceral and a
      psychological stressor in IBS. METHODS: Regional cerebral blood flow measurements
      using H(2)(15)O positron emission tomography were compared across 23 female and
      19 male nonconstipated patients with IBS during a visceral stimulus (moderate
      rectal inflation) and a psychological stimulus (anticipation of a visceral
      stimulus). RESULTS: In response to the visceral stimulus, women showed greater
      activation in the ventromedial prefrontal cortex, right anterior cingulate
      cortex, and left amygdala, whereas men showed greater activation of the right
      dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray.
      Similar differences were observed during the anticipation condition. Men also
      reported higher arousal and lower fatigue. CONCLUSIONS: Male and female patients
      with IBS differ in activation of brain networks concerned with cognitive,
      autonomic, and antinociceptive responses to delivered and anticipated aversive
      visceral stimuli.

PMID- 12806607
TI  - Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial
      cells.
AB  - BACKGROUND & AIMS: Ablation of the enteric glia leads to a fulminant hemorrhagic
      jejunoileitis. We hypothesized that glial-derived neurotrophic factor (GDNF) may
      be involved in mucosal protection of the gut. Therefore, we examined the
      regulation of GDNF and its receptor (GFR-alpha1) in colonic inflammation and its
      effects on colonic epithelial cell apoptosis. METHODS: The expression of GDNF and
      GFR-alpha1 was investigated in experimental colitis of rats and in human
      inflammatory bowel disease (IBD). GDNF-induced activation of Akt (protein kinase
      B [PKB]) and mitogen-activated protein kinase (MAPK) in the colonic epithelial
      cell lines HT-29 and SW480 was studied. Furthermore, the antiapoptotic potency of
      GDNF in SW480 cells was evaluated. RESULTS: GDNF was specifically up-regulated in
      experimental rat colitis and in IBD. In contrast, GFR-alpha1 was constitutively
      expressed in rat and human colonic epithelium. GDNF potently activated MAPK and
      Akt (PKB) in colonic epithelial cells. Moreover, GDNF strongly prevented
      apoptosis in SW480 cells. Our data show that GDNF-mediated protection against
      apoptosis depends on activation of the MAPK and phosphatidylinositol 3-kinase/Akt
      (PKB) pathways. CONCLUSIONS: GDNF is up-regulated in IBD and has strong
      antiapoptotic properties in colonic epithelial cells. This points to a novel role
      of the neurotrophic factor GDNF for mucosal protection and regeneration in IBD.

PMID- 12806608
TI  - Medical decision analysis of chemoprevention against esophageal adenocarcinoma.
AB  - BACKGROUND & AIMS: Chemoprevention of esophageal adenocarcinoma using
      nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of cancer in
      patients with Barrett's esophagus. The aim of the study was to assess the cost
      effectiveness of this strategy. METHODS: The incremental cost-effectiveness ratio
      (ICER) of chemoprevention (compared with endoscopic surveillance or with no
      surveillance) was analyzed with a computer model of a Markov process. RESULTS:
      Under baseline conditions for all patients with Barrett's esophagus (neoplastic
      and nonneoplastic), the ICER of chemoprevention ranges between $12,700 and
      $18,500 US dollars per life-year saved. However, these cost values are sensitive
      to variations in the costs of chemoprevention, incidence of cancer in patients
      with Barrett's esophagus, and efficacy of NSAIDs in reducing the incidence of
      cancer, which can shift the ICER into a cost range that is prohibitively
      expensive. Conversely, in those patients with Barrett's esophagus and high-grade
      dysplasia, the ICER ranges between $3900 and $5000 US dollars. Chemoprevention
      remains a cost-effective option even under rather unfavorable conditions, such as
      higher cost and lower efficacy of chemoprevention and lower incidence of cancer.
      CONCLUSIONS: This model suggests that a high incidence of esophageal
      adenocarcinoma in high-grade dysplasia renders chemoprevention cost-effective
      even in the presence of less-favorable conditions. However, chemoprevention may
      not be a cost-effective measure in the general population of all patients with
      Barrett's esophagus, depending on unknown factors such as cost and efficacy of
      chemoprevention as well as true incidence of cancer.

PMID- 12806609
TI  - Starling of Starling's Law.

PMID- 12806610
TI  - Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of
      concordance and clinical characteristics.
AB  - BACKGROUND & AIMS: In 1988, we reported the first twin study in inflammatory
      bowel disease. The aim of the current study was to follow up these twins
      regarding new cases of inflammatory bowel disease and Crohn's disease
      characteristics using the Vienna classification. METHODS: The official Swedish
      population register and the cause of death register were used to search for the
      twins. All living patients were interviewed. RESULTS: Three monozygotic twins
      earlier classified as healthy had been diagnosed with inflammatory bowel disease
      (ulcerative colitis, n = 2; Crohn's disease, n = 1). Retrospectively, all 3 were
      symptomatic at the original survey. This changed the pair concordance in
      monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to
      50.0% in Crohn's disease. A high degree of concordance regarding age at
      diagnosis, disease location at diagnosis and during the course, and disease
      behavior was found in concordant monozygotic twin pairs with Crohn's disease.
      Seven of 9 pairs were identical in 3 or more of these disease characteristics
      compared with an expected number of 1.5 (P = 0.000076). CONCLUSIONS: This study
      confirms that the genetic influence is stronger in Crohn's disease than in
      ulcerative colitis. A remarkable phenotype similarity within concordant pairs
      with Crohn's disease was found using the Vienna classification.

PMID- 12806611
TI  - Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes
      from patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Steroid-refractory Crohn's disease responds to therapy with
      the chimeric anti-tumor necrosis factor (TNF)-alpha antibody infliximab.
      Etanercept, a recombinant TNF receptor/immunoglobulin G fusion protein, is highly
      effective in rheumatoid arthritis but not in Crohn's disease. Because both
      infliximab and etanercept are TNF-alpha-neutralizing drugs, we investigated the
      differences in TNF-alpha-neutralizing capacity and human lymphocyte binding and
      apoptosis-inducing capacity of both molecules. METHODS: We used a nuclear factor
      kappaB reporter assay and a cytotoxicity bioassay to study TNF-alpha
      neutralization by infliximab and etanercept. Lymphocyte binding and apoptosis
      inducing capacity was investigated using fluorescence-activated cell sorter
      analysis, annexin V staining, and cleaved caspase-3 immunoblotting using mixed
      lymphocyte reaction-stimulated peripheral blood lymphocytes (PBL) from healthy
      volunteers and lamina propria T cells from patients with Crohn's disease.
      RESULTS: Both infliximab and etanercept neutralized TNF-alpha effectively.
      Infliximab bound to activated PBL and lamina propria T cells, whereas binding of
      etanercept was equal to a nonspecific control antibody. Infliximab but not
      etanercept induced peripheral and lamina propria lymphocyte apoptosis when
      compared with a control antibody. Infliximab activated caspase 3 in a time
      dependent manner, whereas etanercept did not. CONCLUSIONS: Although both
      infliximab and etanercept showed powerful TNF-alpha neutralization, only
      infliximab was able to bind to PBL and lamina propria T cells and subsequently to
      induce apoptosis of activated lymphocytes. These data may provide a biological
      basis for the difference in efficacy of the 2 TNF-alpha-neutralizing drugs.

PMID- 12806612
TI  - Diclofenac reduces the incidence of acute pancreatitis after endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND & AIMS: Acute pancreatitis following endoscopic retrograde
      cholangiopancreatography presents a unique opportunity for prophylaxis and early
      modification of the disease process because the initial triggering event is
      temporally well defined and takes place in the hospital. We report a prospective,
      single-center, randomized, double-blind controlled trial to determine if rectal
      diclofenac reduces the incidence of pancreatitis following
      cholangiopancreatography. METHODS: Entry to the trial was restricted to patients
      who underwent endoscopic retrograde pancreatography or had manometrically
      verified sphincter of Oddi hypertension. Immediately after endoscopy, patients
      were given a suppository containing either 100 mg diclofenac or placebo.
      Estimation of serum amylase levels and clinical evaluation were performed in all
      patients. RESULTS: A total of 220 patients entered the trial, and 110 received
      rectal diclofenac. Twenty-four patients developed pancreatitis (11%), of whom 7
      received rectal diclofenac and 17 received placebo (P < 0.05). CONCLUSIONS: This
      trial shows that rectal diclofenac given immediately after endoscopic retrograde
      cholangiopancreatography can reduce the incidence of acute pancreatitis.

PMID- 12806613
TI  - Nutritional supplementation with branched-chain amino acids in advanced
      cirrhosis: a double-blind, randomized trial.
AB  - BACKGROUND & AIMS: The role of oral supplementation with branched-chain amino
      acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach
      might prevent progressive liver failure and improve nutritional parameters and
      quality of life. METHODS: A multicenter, randomized study comparing 1-year
      nutritional supplementation with BCAA against lactoalbumin or maltodextrins was
      performed in 174 patients with advanced cirrhosis. Primary outcomes were the
      prevention of a combined end point (death and deterioration to exclusion
      criteria), the need for hospital admission, and the duration of hospital stay.
      Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh
      score, anorexia, health-related quality of life, and need for therapy. RESULTS:
      Treatment with BCAA significantly reduced the combined event rates compared with
      lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19-0.96; P = 0.039)
      and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95%
      confidence interval, 0.23-1.17; P = 0.108). The average hospital admission rate
      was lower in the BCAA arm compared with control treatments (P = 0.006 and P =
      0.003, respectively). In patients who remained in the study, nutritional
      parameters and liver function tests were, on average, stable or improved during
      treatment with BCAA and the Child-Pugh score decreased (P = 0.013). Also,
      anorexia and health-related quality of life (SF-36 questionnaire) improved. Long
      term compliance with BCAA was poor. CONCLUSIONS: In advanced cirrhosis, long-term
      nutritional supplementation with oral BCAA is useful to prevent progressive
      hepatic failure and to improve surrogate markers and perceived health status. New
      formulas are needed to increase compliance.

PMID- 12806614
TI  - UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of
      chronic pancreatitis and pancreatic cancer.
AB  - BACKGROUND & AIMS: Chronic pancreatitis and pancreatic adenocarcinoma are
      associated with alcohol abuse, consumption of tobacco smoke, and environmental
      aromatic hydrocarbon exposure. The role of genetic factors is incompletely
      defined. Uridine 5'-diphosphate glucuronosyltransferases are phase II detoxifying
      enzymes capable of tobacco-borne toxicant inactivation and cellular protection.
      This study analyzes UGT1A7 gene polymorphisms in pancreatic diseases. METHODS:
      Genomic DNA from northern German white patients with pancreatic adenocarcinoma (n
      = 52) and chronic pancreatitis (n = 146), as well as healthy blood donors (n =
      235) was analyzed by UGT1A7-specific PCR, sequencing analysis, and temperature
      gradient gel electrophoresis. Pancreatic expression of UGT1A genes was identified
      by duplex reverse-transcription PCR. RESULTS: Predominant expression of the
      UGT1A7 gene was identified in human pancreatic tissue. Pancreatic adenocarcinoma
      was associated with the low detoxification activity UGT1A7*3 allele, which
      combines the W208R, N129K, and R131K mutations (odds ratio [OR], 1.98; 95%
      confidence interval [CI ], 1.24-3.14; P = 0.003). The association of UGT1A7*3 was
      especially strong in smokers with pancreatic carcinoma who were younger than 55
      years (OR, 4.7; 95% CI, 1.9-11.8; P = 0.0009). Chronic pancreatitis was also
      associated with UGT1A7*3 (OR, 1.76; 95% CI, 1.26-2.46; P = 0.0009). UGT1A7*3 was
      specifically associated with the subgroup of patients with alcoholic
      pancreatitis, of whom 89% were smokers (OR, 2.24; 95% CI, 1.46-3.43; P = 0.0001)
      but was not associated with the nonalcoholic pancreatitis subgroup. CONCLUSIONS:
      The UGT1A7 gene is predominantly expressed in human pancreas. The low
      detoxification activity UGT1A7*3 allele is identified as a novel risk factor of
      pancreatic diseases defining the interaction of genetic predisposition and
      environmentally induced oxidative injury.

PMID- 12806615
TI  - Relevance of hepatitis B core gene deletions in patients after kidney
      transplantation.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is a major cause of death in
      the long-term follow-up after organ transplantation and immunosuppressive
      therapy. The selection pressure on the HBV genome in these patients is reduced.
      The aim was to analyze and characterize variations in the HBV core gene after
      organ transplantation and their impact for prognosis. METHODS: In patients with
      chronic HBV infection after organ transplantation (liver, n = 60; heart, n = 50;
      kidney, n = 30) the HBV core gene was amplified by polymerase chain reaction
      (PCR). Core gene deletions were cloned into replication competent and expression
      vectors. The impact of these mutations on HBV replication and capsid formation
      was analyzed and correlated with disease progression. RESULTS: Central core gene
      deletions only were detected in patients after kidney transplantation. Two types
      of core gene deletions--small and large--were found. Large core gene deletions
      showed no capsid formation and HBV replication, which resulted in nuclear core
      expression. The occurrence of large core gene deletions was associated with a
      severe course of liver disease. CONCLUSIONS: Core gene deletions occur
      specifically after kidney transplantation. Only large core gene deletions
      resulted in impaired capsid formation and nuclear localization of the core
      protein. The presence of large core gene deletions was associated with
      progressive disease.

PMID- 12806616
TI  - Relation of elevated serum alanine aminotransferase activity with iron and
      antioxidant levels in the United States.
AB  - BACKGROUND & AIMS: Oxidative stress is thought to play a role in liver injury.
      Hepatic iron may promote liver injury, whereas antioxidant vitamins and minerals
      may inhibit it, but few clinical studies have examined such relationships. We
      analyzed the associations of serum iron measures and antioxidant concentrations
      with abnormal serum alanine transaminase (ALT) activity in a large, national,
      population-based study. METHODS: A total of 13,605 adult participants in the
      third U.S. National Health and Nutrition Examination Survey (NHANES III), 1988
      1994, underwent phlebotomy. Exclusions included excessive alcohol consumption,
      hepatitis B and C, and iron overload. RESULTS: Elevated ALT levels were found in
      3.1% of the population. In univariate analysis, factors associated with abnormal
      ALT levels (P < 0.05) included higher transferrin saturation and iron and
      selenium concentrations, and lower vitamin C, alpha and beta carotene, and
      lutein/zeaxanthin concentrations. In multivariate logistic regression analyses,
      elevated ALT level was associated positively with increasing deciles of
      transferrin saturation (odds ratio [OR] per decile, 1.10; 95% confidence interval
      [CI], 1.03-1.18) and iron concentration (OR, 1.13; 95% CI, 1.06-1.21). Abnormal
      ALT level was associated negatively with increasing deciles of alpha carotene
      (OR, 0.82; 95% CI, 0.72-0.94), beta carotene (OR, 0.91; 95% CI, 0.86-0.96), beta
      cryptoxanthin (OR, 0.91; 95% CI, 0.84-0.99), lutein/zeaxanthin (OR, 0.90; 95% CI,
      0.84-0.96), and a variable combining the 5 carotenoid measures (OR, 0.89; 95% CI,
      0.83-0.95). Vitamin C was associated inversely, but only at the highest
      concentrations. CONCLUSIONS: In this large, national, population-based study, the
      risk for apparent liver injury was associated with increased iron and decreased
      antioxidants, particularly carotenoids.

PMID- 12806617
TI  - Down-regulation of the dual-specificity phosphatase MKP-1 suppresses
      tumorigenicity of pancreatic cancer cells.
AB  - BACKGROUND & AIMS: In both pancreatic cancer and chronic pancreatitis, there is
      enhanced expression of mitogenic growth factors and their tyrosine kinase
      receptors, which have the capacity to activate mitogen-activated protein kinase
      (MAPK). In view of the important role of MAPK kinase phosphatase (MKP)-1 in the
      regulation of MAPK activation, the expression and functional role of MKP-1 was
      analyzed. METHODS: Pancreatic tissues were analyzed by Northern blotting, Western
      blotting, and immunohistochemistry. Pancreatic cancer cells were transfected with
      a full-length MKP-1 antisense construct. Growth characteristics and
      tumorigenicity in vivo and the effects of mitogenic growth factors on cell growth
      and MAPK activation were determined in transfected and control cells. RESULTS:
      MKP-1 messenger RNA (mRNA) levels were increased in pancreatic cancer and chronic
      pancreatitis (CP) tissues. Moderate to strong MKP-1 immunoreactivity was present
      in the cancer cells, ductal cells of pancreatic intraepithelial neoplasia, and in
      tubular complexes in CP. Down-regulation of MKP-1 resulted in decreased anchorage
      dependent and -independent growth of pancreatic cancer cells, and decreased
      tumorigenicity in a nude mouse tumor model. MKP-1 down-regulation led to
      decreased proliferation and sustained MAPK activation in response to mitogens.
      CONCLUSIONS: Suppression of MKP-1 expression reduces the tumorigenicity of
      pancreatic cancer cells in vivo, suggesting that MKP-1 contributes to enhanced
      mitogenic signaling in pancreatic cancer cells.

PMID- 12806618
TI  - Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce
      platelet aggregation.
AB  - BACKGROUND & AIMS: Clinical studies have suggested an association between
      cardiovascular disease and infection with Helicobacter pylori. We examined the
      effect of H. pylori on platelets and the mechanism of the interaction. METHODS:
      Three of 5 strains of H. pylori induced platelet aggregation with a lag time of 5
      +/- 2 minutes that was independent of the toxigenic genes cagA and vacA.
      Aggregation was inhibited completely by aspirin and a glycoprotein (GP) IIb/IIIa
      antagonist. Aggregation also was inhibited by monoclonal antibodies that
      prevented the von Willebrand factor (vWF) interaction with GPIb. vWF-coated H.
      pylori bound to cells transfected with GPIbalpha but not to mock transfected
      cells and this was inhibited by an antibody to GPIb. RESULTS: The interaction
      with platelets appeared to be mediated by vWF because platelet aggregation was
      blocked by an antibody to vWF. Moreover, a strain of H. pylori that induced
      platelet aggregation bound vWF to a greater extent than a nonaggregating strain.
      Aggregation also required IgG and could be inhibited by an antibody to the
      platelet IgG receptor (FcgammaRIIA). CONCLUSIONS: Some strains of H. pylori
      induce platelet activation mediated by H. pylori-bound vWF interacting with GPIb,
      and supported by IgG. These platelet-H. pylori interactions may contribute to the
      pathogenesis of H. pylori-associated peptic ulcer disease and to the association
      between H. pylori infection and cardiovascular disease, whereas local platelet
      effects may contribute to the pathogenesis of H. pylori-associated peptic ulcer
      disease.

PMID- 12806619
TI  - IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is
      dependent on a PKCzeta-ROS pathway.
AB  - BACKGROUND & AIMS: Intestinal myofibroblasts (IMFs) express cyclooxygenase 2 (COX
      2) early on in polyp progression and respond to pro-inflammatory cytokines.
      Interleukin (IL)-1alpha induces COX-2 expression in IMF via mitogen-activated
      protein kinase (MAPK), protein kinase C (PKC), and nuclear factor kappa B (NF
      kappaB)-dependent pathways. Because NF-kappaB activity can be mediated by PKC
      activation and reactive oxygen species (ROS) generation, we examined the
      relationship of these pathways to IL-1alpha-induced COX-2 expression. METHODS:
      The effects of specific PKC inhibitors and antioxidants on PKC activation, ROS
      generation, and COX-2 expression were studied. RESULTS:
      Immunoprecipitation/kinase (IPK) analysis showed that IL-1alpha increased PKC
      alpha, delta, and zeta activity 4.5-, 3.1-, and 2.6-fold, respectively, within 5
      minutes. Single-cell fluorescence microscopy of 2',7'-dichlorofluorescin
      diacetate (DCF)-loaded cells showed that IL-1alpha increased ROS levels 2-fold
      within 15 minutes and this increase was inhibited by 10 micromol/L
      bisindolylymaleimide I (BIS), a pan-specific PKC inhibitor that also inhibits COX
      2 expression. Chelerythrine chloride (CC) (0.5 micromol/L) inhibited classic and
      novel PKC activity, but not PKCzeta, and enhanced IL-1alpha-mediated ROS
      generation 4.0-fold and COX-2 expression 1.8-fold. The use of a PKCzeta
      pseudosubstrate prevented IL-1 from increasing ROS greater than control levels
      and abolished IL-1alpha-induced COX-2 expression. Small inhibitory RNA (siRNA)
      for PKCzeta confirmed its role in COX-2 expression. Antioxidants inhibited ROS
      generation and diminished IL-1alpha-induced COX-2 expression by 80%, without
      affecting PKC activation. Neither the PKC inhibitors nor the antioxidants
      prevented NF-kappaB-mediated transcription as determined by reporter gene
      analysis. CONCLUSIONS: PKCzeta and threshold ROS generation are critical for IL
      1alpha-induced COX-2 expression and act concomitantly with NF-kappaB
      translocation in IMF.

PMID- 12806620
TI  - Intestinal myofibroblasts in innate immune responses of the intestine.
AB  - BACKGROUND & AIMS: Intestinal myofibroblasts are known to respond to inflammatory
      signals and may play a role in Crohn's disease-associated fibrosis. However,
      putative involvement by myofibroblasts in innate immune responses as part of
      intestinal host defense has not been characterized. We therefore analyzed
      expression and regulation of toll-like receptors (TLRs) in colonic human
      myofibroblasts (CCD-18) and primary human colonic myofibroblasts in comparison
      with human lung myofibroblasts (CCD-37). METHODS: Expression of TLRs (1-10) and
      NOD 1 and 2 was assessed before and after stimulation with either
      lipopolysaccharide (LPS) or lipoteichoic acid (LTA) by using a custom microarray,
      reverse-transcription polymerase chain reaction, Northern blot and Western blot
      analysis, and immunohistochemistry. Activation of signaling pathways,
      translocation of p65, and secretion of interleukin (IL)-8 were determined.
      RESULTS: Messenger RNAs encoding for TLR1-9, as well as NOD1 and NOD2, were
      amplified from cultured and primary human intestinal myofibroblasts. After
      stimulation with LPS or LTA, a 1.5-4.2-fold up-regulation of TLRs (2, 3, 4, 6, 7)
      and elements of the signaling cascade (MyD88, TIR domain-containing adapter
      protein [TIRAP]) was observed. CCD-18 and CCD-37 cells expressed TLR 2 and 4
      protein, which were located primarily on the cell membrane. Stimulation with LTA
      or LPS resulted in activation of the mitogen-activated protein kinases pathway,
      nuclear translocation of p65, and significantly increased IL-8 secretion.
      CONCLUSIONS: Bacterial components directly activate intestinal myofibroblasts
      expressing TLRs. These cells may therefore participate in innate immune responses
      by sensing and responding to bacterial products that have penetrated into the
      subepithelial compartment.

PMID- 12806622
TI  - Human cord blood-derived cells can differentiate into hepatocytes in the mouse
      liver with no evidence of cellular fusion.
AB  - BACKGROUND & AIMS: Studies have indicated that stem cells have unexpected
      plasticity and can differentiate down a multitude of nonhematopoietic cell
      lineages in rodents. Our aim was to identify whether human cord blood cells,
      which are a rich source of stem cells, would be able to differentiate into
      hepatocytes when infused into nonobese diabetic-severe combined immunodeficient
      (NOD-SCID) mice. We also wanted to test whether such differentiated cells were
      the result of cellular fusion or true stem cell transdifferentiation. METHODS:
      Unsorted mononuclear cell preparations of human cord blood were infused into
      sublethally irradiated NOD-SCID mice. After death, immunohistologic analysis of
      murine livers was performed using human specific hepatocyte, biliary, and
      endothelial markers. Fluorescent in situ hybridization (FISH) for mouse and human
      DNA was also performed. RESULTS: We show that human cord blood cells have the
      ability to engraft into NOD-SCID liver and become mature hepatocytes. We were
      unable to identify any biliary or endothelial differentiation. Furthermore, we do
      not detect any evidence of cell fusion in any of the human cells found in the
      mouse liver, suggesting that human cord blood cells are capable of true
      transdifferentiation into hepatocytes in vivo. CONCLUSIONS: We conclude that
      hepatocytes can derive from human cord blood cells when infused into NOD-SCID
      mice in the absence of fusion. The demonstration that human stem cell
      differentiation can occur in this murine model permits comprehensive study of
      human stem cell plasticity in vivo.

PMID- 12806621
TI  - Host and microbial constituents influence Helicobacter pylori-induced cancer in a
      murine model of hypergastrinemia.
AB  - BACKGROUND & AIMS: Helicobacter pylori cag(+) strains and high-expression host
      interleukin 1beta (IL-1beta) polymorphisms augment the risk for intestinal-type
      gastric adenocarcinoma, a malignancy that predominates in males. We examined the
      effects of an H. pylori cancer-associated determinant (cagE), IL-1beta, and host
      gender in a transgenic hypergastrinemic (INS-GAS) murine model of gastric
      carcinogenesis. METHODS: Male and female INS-GAS mice infected with wild-type H.
      pylori, an H. pylori cagE(-) mutant, or H. felis were killed 2-24 weeks
      postchallenge. Gastric injury was scored from 0 to 4, and mucosal IL-1beta levels
      were quantified by ELISA. RESULTS: Male INS-GAS mice infected with H. pylori
      uniformly developed atrophy, intestinal metaplasia, and dysplasia by 6 weeks and
      carcinoma by 24 weeks. Mucosal IL-1beta concentrations increased 12 weeks
      following Helicobacter challenge, but levels then decreased by 24 weeks.
      Inactivation of cagE delayed the progression to carcinoma, but neoplasia
      ultimately developed in all males infected with the H. pylori mutant. In
      contrast, none of the H. pylori-infected female mice developed cancer, and injury
      scores, but not IL-1beta levels, were significantly higher in males compared with
      females. CONCLUSIONS: H. pylori infection induces gastric adenocarcinoma in an
      experimental mouse model of disease. Cancer is restricted to males and loss of
      cagE temporally retards but does not abrogate pathologic progression. Mucosal
      levels of IL-1beta increase prior to the development of gastric cancer but are
      not related to gender. The INS-GAS model is effective for investigating discrete
      host-microbial interactions that culminate in gastric cancer within the context
      of biologic conditions induced by H. pylori.

PMID- 12806623
TI  - Transgenic overexpression of the oncofetal RNA binding protein KOC leads to
      remodeling of the exocrine pancreas.
AB  - BACKGROUND & AIMS: To elucidate the function of the oncofetal RNA-binding
      protein, K-homologous (KH) domain containing protein overexpressed in cancer
      (KOC), we studied the effect of a constitutive reexpression of KOC in transgenic
      mice. METHODS: Transgenic mouse lines expressing KOC under the control of the
      mouse metallothionein promoter were generated and were shown to express the 69
      kilodalton protein. Two mouse lines with moderate to strong gene expression of
      the transgene were further analyzed. RESULTS: The pancreas of KOC-transgenic mice
      showed progressive morphologic alterations, including an increased proliferation
      of acinar cells, acinar-ductal metaplasia, net loss of acinar tissue, and the
      appearance of numerous interstitial cells. Acinar-ductal metaplasia led to the
      development of duct-like structures exhibiting the characteristics of normal
      intralobular ducts. Interstitial cells expressed markers of endocrine or ductal
      differentiation. Nerve growth factor alpha (NGF-alpha) and the GTPase kir/Gem
      were identified as potential targets of KOC by expression profiling analyses.
      CONCLUSIONS: Reexpression of KOC in the transgenic model is apparently
      incompatible with the maintenance of a fully differentiated, adult acinar
      phenotype and may lead to a more fetal ductal phenotype via acinar-ductal
      metaplasia. This and the appearance of interstitial cells with a ductal and
      endocrine differentiation capacity suggest that transgenic reexpression of the
      oncofetal gene KOC may recapitulate a developmental program active during
      embryogenesis.

PMID- 12806624
TI  - Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: The mechanism for development of primary biliary cirrhosis
      (PBC) remains enigmatic, but molecular mimicry has been implicated because of
      well-known cross-reactivity of human mitochondrial autoantigens and equivalent
      bacterial antigens. Virtually all patients with PBC have antimitochondrial
      autoantibodies (AMA), but, interestingly, approximately 50% also manifest
      antinuclear antibodies (ANA). METHODS: To determine whether generation of ANA are
      due to molecular mimicry of mitochondrial peptides, we established 6 T-cell
      clones selected by a peptide corresponding to the E2 subunit of mitochondrial
      pyruvate dehydrogenase complex and analyzed for reactivity to mimicry peptides
      derived from mitochondrial and nuclear autoantigens, including control sequences.
      RESULTS: For mitochondrial autoantigens, 1 peptide from the E2 subunit of the
      pyruvate dehydrogenase complex, 1 peptide from the E2 subunit of the oxo
      glutarate dehydrogenase complex, 1 peptide from the E2 subunit of the branched
      chain 2-oxoacid dehydrogenase complex, and 1 peptide from the E3-binding protein
      cross-reacted with these T-cell clones. For the nuclear autoantigens, 5 peptides
      from gp210 and 1 from Sp100 cross-reacted with these clones. Furthermore, 1 of 3
      T-cell clones selected by recombinant gp210 protein reacted with a mimicry
      peptide corresponding to amino acids 188-201 of gp210, indicating that this part
      of the protein is a naturally processed immunodominant T-cell epitope.
      CONCLUSIONS: These results demonstrate molecular mimicry between mitochondrial
      and nuclear autoantigens in PBC and that a mimicry peptide may become an
      immunodominant T-cell epitope. These data have significance not only for PBC but
      also for the production of ANA in other disease processes.

PMID- 12806626
TI  - Refractory heartburn.

PMID- 12806625
TI  - FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative
      feedback control of FXR activity.
AB  - BACKGROUND & AIMS: Bile acids are essential for bile formation and intestinal
      absorption of lipids and fat-soluble vitamins. However, the intrinsic toxicity of
      hydrophobic bile acids demands a tight control of their intracellular
      concentrations. Bile acids are ligands for the farnesoid X receptor (FXR) that
      regulates the expression of genes controlling bile acid synthesis and transport.
      The human uridine 5'-diphosphate-glucuronosyltransferase 2B4 (UGT2B4) converts
      hydrophobic bile acids into more hydrophilic glucuronide derivatives. In this
      study, we identify UGT2B4 as an FXR target gene. METHODS: Human hepatocytes or
      hepatoblastoma HepG2 cells were treated with chenodeoxycholic acid or the
      synthetic FXR agonist GW4064, and the levels of UGT2B4 messenger RNA, protein,
      and activity were determined by using real-time polymerase chain reaction,
      Western blot, and glucuronidation assays. RESULTS: Treatment of hepatocytes and
      HepG2 cells with FXR agonists resulted in an increase of UGT2B4 messenger RNA,
      protein, and activity. A bile acid response element in the UGT2B4 promoter (B4
      BARE) to which FXR, but not retinoid X receptor, binds, was identified by site
      directed mutagenesis, electromobility shift, and chromatin immunoprecipitation
      assays. Retinoid X receptor activation abolished the induction of UGT2B4
      expression and inhibited binding of FXR to the B4-BARE, suggesting that retinoid
      X receptor modulates FXR target gene activation. Overexpression of UGT2B4 in
      HepG2 cells resulted in the attenuation of bile acid induction of the FXR target
      gene small heterodimeric partner. CONCLUSIONS: These data suggest that UGT2B4
      gene induction by bile acids contributes to a feed-forward reduction of bile acid
      toxicity and a decrease of the activity of these biological FXR activators.

PMID- 12806627
TI  - Spontaneous resolution of chronic hepatitis C virus disease after withdrawal of
      immunosuppression.
AB  - Approximately 85% of acute cases of hepatitis C infection result in chronic
      hepatitis. Spontaneous clearance of hepatitis C virus has been thought to occur
      exclusively after acute infection and is associated with a robust cellular immune
      response. We describe here a case of a renal transplant recipient who acquired
      posttransplant hepatitis C virus infection with rapid histological progression
      but who subsequently experienced spontaneous viral clearance along with
      histological remission after removal of immunosuppression. Immunologic studies
      showed persistently strong cellular immune responses. This case underscores the
      importance of restoration of the immune system in the control of hepatitis C
      virus viremia and disease progression and the need to minimize or obviate
      immunosuppression in organ transplant recipients.

PMID- 12806628
TI  - Severe villus atrophy and chronic malabsorption induced by azathioprine.
AB  - Azathioprine is commonly prescribed for autoimmune hepatitis and inflammatory
      bowel disease. An acute gastroenteritis-like syndrome has been ascribed to
      azathioprine use, but chronic diarrhea has not. We report a patient with
      autoimmune hepatitis who developed severe small-bowel villus atrophy and chronic
      diarrhea after azathioprine was initiated (50 mg/day). We present a case report
      of a patient followed up prospectively. Duodenal mucosal histology and expression
      of brush border enzyme dipeptidyl peptidase IV and peptide transporter PepT1
      messenger RNA levels were determined before and after azathioprine
      discontinuation. Chronic diarrhea developed several weeks after the initiation of
      azathioprine and resulted in micronutrient depletion and severe protein-calorie
      malnutrition, which was unresponsive to oral pancreatic enzyme therapy or a
      gluten-free diet. Severe malabsorption required parenteral nutrition support for
      longer than 1.5 years; this was complicated by unstable blood glucose control,
      acute calculous cholecystitis, catheter sepsis, and severe venous thrombosis.
      When the temporal association between azathioprine and diarrhea was identified,
      the drug was tapered while the patient consumed an unrestricted diet. Within 2
      weeks after azathioprine was discontinued, diarrhea had completely resolved, and
      parenteral nutrition was discontinued. Mucosal biopsies obtained before and 4
      months after azathioprine discontinuation showed complete reversal of severe
      duodenal villus atrophy and marked up-regulation of mucosal dipeptidyl peptidase
      IV and PepT1 messenger RNA. The patient has subsequently maintained normal liver
      function tests on low-dose prednisone alone, with normal stools and stable
      nutritional status for longer than 4 years. Azathioprine can induce severe small
      bowel villus atrophy, diarrhea, and malabsorption that is reversible with drug
      discontinuation.

PMID- 12806629
TI  - A "catastrophic hypothesis" for pancreas cancer progression.
AB  - Exocrine pancreas cancer has a dismal prognosis. The precise reasons accounting
      for its biological and clinical behavior are not known. A "catastrophe" takes
      place in the course of pancreas cancer development/progression so that, once it
      occurs, the evolution of the tumor is very rapid, leading to local invasion and
      metastasis. Up to now, such behavior cannot be conclusively ascribed to a single
      molecular event. If correct, this hypothesis has important implications regarding
      pancreas cancer research. Further work is warranted to examine this hypothesis
      and to identify the putative "catastrophic" elements participating in this tumor.

PMID- 12806630
TI  - Presentation of the Julius M. Friedenwald Medal to Tadataka Yamada, M.D.

PMID- 12806631
TI  - Fecal calprotectin in Crohn's disease: new family ties.

PMID- 12806632
TI  - Further characterization of human brain processing of viscero-sensation: the role
      of gender and a word of caution.

PMID- 12806633
TI  - Prevention of post-ERCP pancreatitis: pharmacologic solution or patient selection
      and pancreatic stents?

PMID- 12806634
TI  - Branched-chain amino acid-enriched supplements as therapy for liver disease:
      Rasputin lives.

PMID- 12806635
TI  - A hitchhiker's guide to the galaxy--an H. pylori travel guide.

PMID- 12806636
TI  - How safe are the safest IBD drugs?

PMID- 12806638
TI  - Maintenance infliximab therapy in patients with Crohn's disease: how long, how
      much, how frequent?

PMID- 12806639
TI  - Infliximab in ulcerative colitis: is there a placebo (effect) in the house?

PMID- 12806641
TI  - Look ma, no blades.

PMID- 12806642
TI  - "A la carte" treatment of portal hypertension or just "hors d'oeuvres".

PMID- 12806661
TI  - [Microterrorists with own agenda].

PMID- 12806662
TI  - [From epilepsy to epilepsies].

PMID- 12806663
TI  - [Information and use of drugs].

PMID- 12806664
TI  - [When can the diagnosis of multiple sclerosis be confirmed?].

PMID- 12806665
TI  - [Thrombolytic therapy and/or angioplasty?].

PMID- 12806666
TI  - [Does the list patient system function?].

PMID- 12806667
TI  - [List patient system--expectations and experiences].

PMID- 12806668
TI  - [General practitioners' experiences with the list patient system].

PMID- 12806669
TI  - [Influence of the list patient system on the increase of emergency ward
      attendance].

PMID- 12806670
TI  - [Coronary angioplasty after failed thrombolytic therapy in acute myocardial
      infarction].

PMID- 12806671
TI  - [Selective COX-2 inhibitors--attitudes and prescription habits among general
      practitioners].

PMID- 12806672
TI  - [COX-2 inhibitors and their effects on kidney and blood pressure].

PMID- 12806673
TI  - [Fontan circulation is associated with thrombosis].

PMID- 12806674
TI  - [New diagnostic criteria in multiple sclerosis].

PMID- 12806676
TI  - [Prehospital ECG reduces time to treatment with percutaneous coronary
      interventions].

PMID- 12806675
TI  - [Use of MR in the diagnosis of multiple sclerosis].

PMID- 12806677
TI  - [Use and misuse of antibacterial agents in chronic bronchitis].

PMID- 12806678
TI  - [What is epilepsy?].

PMID- 12806679
TI  - [Epileptic syndromes in children].

PMID- 12806680
TI  - [The Norwegian registry of joint prostheses--15 beneficial years for both the
      patients and the health care].

PMID- 12806681
TI  - [Research and specialty associations of the Medical Society].

PMID- 12806682
TI  - [Philosophy of life in the medicine of today].

PMID- 12806683
TI  - [On the track of healing stem cells].

PMID- 12806684
TI  - [The Medical Society's choice of way--a serious actor or a marginalized
      professional association?].

PMID- 12806685
TI  - [Therapy of psychoses].

PMID- 12806686
TI  - [Individual preventive measures against cardiovascular diseases--a task for the
      general practitioners?].

PMID- 12806687
TI  - [Individual prevention in general practice].

PMID- 12806688
TI  - [About the benefits of the concept of disease].

PMID- 12806689
TI  - [What does the sick leave cost?].

PMID- 12806690
TI  - [Network therapy of psychoses by means of Jaakko Seikkula ].

PMID- 12806691
TI  - [Omissions of radiologists as co-authors of articles].

PMID- 12806692
TI  - [A differentiated basic contribution to the list patient system?].

PMID- 12806693
TI  - [A new nail to the coffin of the medical profession's academic affiliation].

PMID- 12806694
TI  - [Quality of anticoagulation management in ambulatory care of patients with atrial
      fibrillation].
AB  - Many patients with atrial fibrillation do not receive anticoagulation due to
      accepted contraindications but also due to considerable underuse. We screened
      2215 consecutive patients when they entered the Medical Emergency Department for
      any acute condition. The decision on correct use or underuse of oral
      anticoagulation was made from the charts by consensus of two experienced
      physicians. The prevalence of atrial fibrillation was 3.7%. 43 of 83 patients
      with atrial fibrillation had oral anticoagulation (52%, mean age 76 years). 32
      patients were treated with Aspirin only (38%, mean age 79 years). 29 patients
      (35%) did not receive anticoagulation because of accepted contraindications,
      i.e., dementia and risk for recurrent falls (n = 16), history of bleeding (n =
      6), drug malcompliance due to forgetfulness (n = 4) and psychiatric disease (n =
      1). Underuse of anticoagulation occurred only in three patients (4%, unclear
      reasons in two patients, patient's unwillingness in one patient). CONCLUSION: We
      did not observe substantial underuse of anticoagulation in patients with atrial
      fibrillation.

PMID- 12806695
TI  - [Is it possible to do pharmaco-epidemiological research using electronic
      databanks in the Swiss health care system?].

PMID- 12806696
TI  - [Stent therapy of the carotid artery: a therapeutic alternative to
      endarterectomy].

PMID- 12806697
TI  - [Acute abdominal pain. Splenic infarct of unknown etiology].

PMID- 12806698
TI  - Israel, Iraq, Zimbabwe--should we care?

PMID- 12806699
TI  - Increasing stresses in O & G units in district hospitals.

PMID- 12806700
TI  - Stress and resilience in South African firefighters.

PMID- 12806701
TI  - A note on confidentiality of death notification forms.

PMID- 12806702
TI  - A note on the quality of medical certification of deaths in South Africa, 1997
      2001.

PMID- 12806703
TI  - Poverty alleviation = good medicine.

PMID- 12806704
TI  - Critics say HIV survey potentially biased.

PMID- 12806705
TI  - Letlape lashes out at group self-interest.

PMID- 12806706
TI  - Prisons baulk at AIDS research findings.

PMID- 12806707
TI  - Emergency medicine one step closer.

PMID- 12806708
TI  - Little known killer: Barth syndrome.

PMID- 12806709
TI  - Negotiating a managed care contract.

PMID- 12806711
TI  - The Magpie study--clinical implications for poor countries.

PMID- 12806710
TI  - Laboratory monitoring of HIV/AIDS in a resource-poor setting.

PMID- 12806712
TI  - The pitfalls of translation--a case study based on the translation of the EQ-5D
      into Xhosa.
AB  - There is an evident need for standardised, internationally recognised instruments
      to measure health-related outcomes that are also locally applicable. The European
      Quality of Life 5-Dimensions (EQ-5D) is a widely used measure of health-related
      quality of life (HRQoL) that was translated into Xhosa. This communication
      outlines some of the different cultural and linguistic issues that had to be
      addressed during the translation process. The translation guidelines provided by
      the EuroQol group were followed. This involved both forward and backward
      translations by Xhosa speakers, with consensus meetings after each. Thereafter,
      lay panel respondent testing of the consensus version was performed. Eventually a
      credible Xhosa version of the EQ-5D was produced. Concepts which proved
      surprisingly difficult to transfer across the languages and cultures included
      'mobility', 'confined to bed' and the choice of word to denote 'male'. The
      translation process prompted lengthy discussion and proved more challenging than
      initially anticipated. Despite the rigorous process followed, later additions had
      to be made to the questionnaire after field testing. It would appear that extreme
      caution should be exercised when using a questionnaire in a culture and language
      different from the one in which it was originally developed and validated. If
      this is not done, the validity of cross-cultural research projects may be open to
      question.

PMID- 12806713
TI  - Resting and exercising heart rate before, during and after a 10-day space flight.

PMID- 12806714
TI  - Dysphagia lusoria--a tale to tell and what to do.

PMID- 12806715
TI  - Recommendations pertaining to the use of viral vaccines: influenza. Review of
      influenza activity--2002.

PMID- 12806716
TI  - High prevalence of TT virus in a rural community of South Africa.

PMID- 12806717
TI  - Historical precedents for socioeconomic disparities in growth among South African
      schoolchildren.

PMID- 12806718
TI  - At what age are South African women first having sex?

PMID- 12806719
TI  - Clinical assessment of early gestational age.

PMID- 12806720
TI  - Medical students' experiences of the autopsy.

PMID- 12806721
TI  - Correlation between erythromycin and azithromycin resistance in Streptococcus
      pneumoniae.

PMID- 12806723
TI  - Risk factors for admission and the role of respiratory syncytial virus-specific
      cytotoxic T-lymphocyte responses in children with acute bronchiolitis.
AB  - BACKGROUND: Risk factors for admission of children with acute bronchiolitis have
      remained controversial. Technological advances in the measurements of cytotoxic T
      lymphocyte (CTL) activity, enable respiratory syncytial virus (RSV)-specific CTL
      activity to be studied in infants with bronchiolitis for the first time. We
      evaluated risk factors for admission of children with acute bronchiolitis and
      determined the role of CTL responses in those infected with RSV. METHOD: Children
      between 3 and 24 months of age presenting with bronchiolitis to the paediatric
      outpatient department at King Edward VIII Hospital, Durban, over a 1-year period
      were enrolled. Management included clinical evaluation, nasopharyngeal
      aspiration, standard treatment and hospitalisation if indicated. Secretions were
      tested with monoclonal antibodies for RSV and pooled respiratory viruses; shell
      vial cultures were also established. Permission was requested from parents of RSV
      infected subjects for blood draws for specific cytotoxic T-cell assays and
      CD4/CD8 cells on admission and repeat CTL on day 7. RESULTS: Viruses were
      identified in 55 of the 114 subjects studied (48.2%). RSV was seen in 41 cases
      (74.5%). Twenty-three infants (20.2%) required admission. Risk factors associated
      with inpatient admissions on univariate analysis included younger mean age (7.6
      months v. 10.1 months), overcrowding (p < 0.01) and indoor exposure to products
      of combustion of cooking fuels (p = 0.05). Only the former two were significant
      on multivariate analysis. RSV-specific CTL responses were obtained in 21 children
      (51.2%). Responses were either very weak (N = 7) or negative (N = 14) on day 0
      and did not alter significantly on day 7. The mean CD4/CD8 ratios in this group
      were 2.27:1. The highest frequency of CTL was directed against the proteins
      M4/5/6', with counts ranging from 100 to 400 spot forming cells (sfc)/million.
      CONCLUSION: Measures to address risk factors identified in this study may
      decrease the need for hospitalisation from bronchiolitis. The lack of RSV
      specific CTL responses in peripheral blood of immunocompetent RSV-infected
      children suggest an alternative method of induction of immunity or
      compartmentalisation of immune cells.

PMID- 12806722
TI  - Clinical predictors of outcome in acute upper gastrointestinal bleeding.
AB  - OBJECTIVE: Endoscopy has traditionally been used to risk-stratify patients with
      upper gastrointestinal bleeding (UGIB). This is problematic in resource-poor
      environments. The study aimed to identify patients who would not require urgent
      endoscopy by identifying clinical variables before endoscopy that predict
      uneventful recovery. DESIGN: Prospective, descriptive cross-sectional study.
      SETTING: Groote Schuur Hospital, Cape Town. SUBJECTS: Two hundred consecutive
      patients aged over 12 years, presenting with haematemesis and/or melaena. OUTCOME
      MEASURES: Good outcome, i.e. no blood transfusion, endotherapy or surgery, and
      alive at 1 month following presentation. RESULTS: Eighty patients (40%) had a
      good outcome. Haemoglobin > 10 g/dl (odds ratio (OR) 25.5, 95% confidence
      interval (CI): 8.9-74.8; p < 0.001), absence of melaena (OR 4.8, 95% CI: 1.79
      12.94, p = 0.002) and absence of syncope (OR 4.0, 95% CI: 1.67-9.48; p = 0.002)
      were independent predictors of good outcome. The three variables combined as a
      positive test had the best association with good outcome when compared with a
      single variable or a combination of two variables. The three-variable model had
      sensitivity for good outcome of 34%, specificity of 98%, and likelihood ratio for
      a positive test of 13.5 and for a negative test of 0.68. Thirty patients (15%)
      had the combination for the prediction rule, i.e. haemoglobin > 10 g/dl, no
      melaena and no syncope; 3 (10%) had a poor outcome (required endotherapy).
      CONCLUSION: The prediction rule accurately excluded poor outcome, a priority in
      the clinical context, but did not predict good outcome. Clinical implications are
      a 15% reduction in unnecessary urgent endoscopies, with less than 5% of patients
      with poor outcome not undergoing urgent endoscopy. These findings may have
      particular clinical relevance in under-resourced health care environments.

PMID- 12806724
TI  - Nutritional variation and cardiovascular risk factors in Tanzania--rural-urban
      difference.
AB  - OBJECTIVE: To assess the relationship between dietary factors and cardiovascular
      (CVD) risk factors in middle-aged men and women, in urban, rural and pastoral
      settings in Tanzania. DESIGN: Cross-sectional epidemiological study designed
      according to the protocol of the World Health Organisation (WHO) Cardiovascular
      Diseases and Alimentary Comparison (CARDIAC) study. SETTING: Three centres in
      Tanzania, namely Dar es Salaam (urban), Handeni (rural) and Monduli (pastoral
      population). SUBJECTS: The subjects, aged 47-57 years, were recruited randomly
      from administrative lists available from each centre. OUTCOME MEASURES: Blood
      pressure (BP) was measured using a centrally calibrated automatic BP machine (Khi
      machine). Dietary history of the participants was obtained using a standard
      questionnaire designed on the basis of a seven-day recall system. Height, weight,
      serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDLC),
      haemoglobin A1c, sodium, potassium and magnesium were measured. RESULTS: The
      prevalence of hypertension (BP > or = 140/90 mmHg or antihypertensive drug use),
      obesity (body mass index (BMI) > or = 30 kg/m2) and hypercholesterolaemia (TC >
      5.2 mmol/l) were lowest in the rural area. Consumption of green vegetables, milk,
      coconut milk, meat, and fish varied significantly between the three areas.
      Important determinants for BP among men were BMI (p < 0.001), and salt intake (p
      < 0.05). Among women, TC (p < 0.05), age (p < 0.05), BMI (p < 0.001) and coconut
      milk consumption (p < 0.001) were important BP determinants. Salt intake was
      positively associated with systolic BP (SBP) and diastolic BP (DBP) in men but
      not among women (both SBP and DBP p < 0.05 respectively). Dietary determinants of
      serum TC were meat, fish and green vegetable consumption. CONCLUSION: Differences
      in dietary habits contributed significantly to the urban-rural-pastoral
      variations in CVD risk pattern in Tanzania.

PMID- 12806725
TI  - Illnesses of Herod the Great.
AB  - Herod the Great, Idumean by birth, was king of the Jews from 40 to 4 BC. An able
      statesman, builder and warrior, he ruthlessly stamped out all perceived
      opposition to his rule. His last decade was characterised by vicious strife
      within his family and progressive ill health. We review the nature of his
      illnesses and suggest that he had meningoencephalitis in 59 BC, and that he died
      primarily of uraemia and hypertensive heart failure, but accept diabetes mellitus
      as a possible underlying aetiological factor. The possibility that Josephus'
      classical descriptions of Herod's disease could be biased by 'topos' biography
      (popular at the time), is discussed. The latter consideration is particularly
      relevant in determining the significance of the king's reputed worm infestation.

PMID- 12806726
TI  - [Physician's work is changing--how will it go for the profession?].

PMID- 12806727
TI  - [SARS--is it a global threat or not?].

PMID- 12806728
TI  - [Physician's professional ethics and problems of the health care system].

PMID- 12806729
TI  - [A new type of myotonic dystrophy].

PMID- 12806730
TI  - [Critical thinking is essential for effective usage of pharmaceutical product
      information].

PMID- 12806731
TI  - [Should we stop using the phrase "doctor's order"?].

PMID- 12806732
TI  - [Heredity and the risk of oral cancer].

PMID- 12806734
TI  - [Problematic fever].

PMID- 12806735
TI  - [Ectopic pregnancy].

PMID- 12806736
TI  - [Welcome to visit the new targets in the field of immunology].

PMID- 12806737
TI  - [Immunology as a bioscience].

PMID- 12806738
TI  - [Natural immunity in the front line of defense].

PMID- 12806739
TI  - [Stem cells--the Emperor's new clothes?].

PMID- 12806740
TI  - [Dendritic cell--the conductor of the orchestra of immunological responses].

PMID- 12806741
TI  - [New knowledge about cytokines].

PMID- 12806742
TI  - [Leucocyte migration to the site of inflammation].

PMID- 12806743
TI  - [From magic bullets to real drugs--immunotherapy available on the pharmacy's
      shelves].

PMID- 12806745
TI  - Acute respiratory disorders in the newborn. The lessons to be learnt.

PMID- 12806744
TI  - [Newest tricks how to fool the immune system].

PMID- 12806746
TI  - Issues in bioethics. Ethics and professional responsibilities.
AB  - The evolution of ethics in medicine has provided the concept of the learned
      physician who is trained in the scientific method (studying nature and
      philosophy), and who is wise, modest and humane. The physician's manner,
      deportment and character should be above reproach, and devotion to the productive
      art of medicine should supersede any desire for financial gain. Professionalism
      provides the organizational structure through which the medical doctor performs
      his/her healing role, and underscores the concept that medical professionals
      should be moral and devoted to the public good, displaying altruism at the
      expense of self-interest, and providing accountability. This article examines
      some of the obligations that arise within this milieu.

PMID- 12806747
TI  - In vitro anti-proliferation/cytotoxic activity of cantharidin (Spanish Fly) and
      related derivatives.
AB  - The anti-cancer therapeutic promise of cantharidin is limited because of its high
      mammalian toxicity. In order to find new anti-cancer lead compounds with reduced
      toxicity of the cantharidin prototype, the following seven derivatives were
      screened against the human SH-SY5Y neuroblastoma and MCF-7 breast cancer cells in
      vitro: 2,3-dimethyl-7-oxabicylo-[2.2.1]heptane-2,3-dicarboxylic anhydride
      (cantharidin) [1], 1-cyclohexen-1,2-dicarboxylic anhydride [2], cis-4-cyclohexen
      1,2-dicarboxylic anhydride [3], cis-1, 2-cyclohexanedicarboxylic anhydride [4],
      exo-7-oxabicyclo[2.2.1]hept-5-ene-2-3 dicarboxylic anhydride [5], exo-7
      oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride (norcantharidin) [6], and (S)
      (-)-O-acetylmalic anhydride [7]. Cantharidin, was found to be the most effective
      anti-proliferative compound on both cell lines. However, on the human
      neuroblastoma cells cantharidin was of equal toxicity to compound [6]. Mode of
      action studies revealed that cantharidin inhibited growth factor-mediated
      activation of mitogen activated protein kinase (MAPkinase) and attenuated the de
      phosphorylation of the extracellular regulated kinases 1 and 2 (erk1 and erk2).

PMID- 12806748
TI  - A serosurvey of hepatitis B virus, hepatitis C virus, human T lymphotropic virus
      type-1 and syphilis in HIV-1-infected patients in Jamaica.
AB  - The seroprevalences of hepatitis B virus (HBV), hepatitis C virus (HCV), human T
      lymphotropic virus type-1 (HTLV-1) and syphyilis were determined in 129 HIV-1
      infected patients using commercially prepared reagents. The seroprevalences were
      HCV, 0% (0/129); HBV, 37% (48/129); HTLV-1, 5% (6/129) and syphilis, 20%
      (26/129). Fifteen per cent (19/129) of the patients had active/chronic HBV
      infection. The seroprevalence of HBV was statistically significantly higher in
      HIV-1 infected men (24/49, 50% versus 17/80, 21%; p = 0.005), while the
      seroprevalence of syphilis was statistically significantly increased in HIV-1
      infected patients in the over-40 age group (10/31, 32% versus 6/53, 11%; p =
      0.05). These findings throw the spotlight on HBV infection and syphilis and
      suggest that these two sexually transmitted infections should be carefully
      surveyed in patients with HIV/AIDS in Jamaica. It is essential for management
      protocols in Jamaica to include screening for evidence of these co-infections.

PMID- 12806750
TI  - Acute respiratory disorders in the newborn at the Mount Hope Women's Hospital,
      Trinidad.
AB  - This retrospective study was undertaken to determine the incidence of acute
      respiratory disorders (ARD) in newborns delivered at the Mount Hope Women's
      Hospital (MHWH) from January 1 to December 31, 1994. The study also examined the
      relationships between incidence rate of ARD and maternal and neonatal parameters.
      Hyaline membrane disease (HMD), transient tachypnoea of the newborn (TTN),
      meconium aspiration syndrome (MAS), persistent fetal circulation (PFC) and
      pulmonary infection (PI) were identified as ARDs among 5062 live newborns using
      standard diagnostic criteria. Overall, 174/5062 neonates were diagnosed with ARD
      to give an incidence of 3.4% (104 males and 70 females). The most common ARD was
      PI (39%) followed by HMD (29%). The incidence of ARD in preterm infants was 20.6%
      (100/486) and 1.1% (48/4363) in term neonates. Hyaline membrane disease occurred
      mainly in the preterm and low birthweight babies. Transient tachypnoea of the
      newborn and PI were found in all gestational age groups. Asphyxia was present in
      10.9% (19/174) at five minutes of age. It was more common in babies who developed
      HMD and PFC. Forty-one per cent (71/174) of babies with ARD required assisted
      ventilation. There were 58/174 (33%) deaths. More than a half of those ventilated
      died (39/71 or 55%); 2/3 of those with airleaks and all those with
      intraventricular haemorrhage died. Mortality was significantly associated with
      asphyxia at both one and five minutes of age. There was significantly greater
      mortality among neonates with HMD as compared to the other ARDs.

PMID- 12806749
TI  - Mortality among HIV-infected paediatric patients in Barbados.
AB  - Since the onset of the HIV epidemic, AIDS has become the leading cause of
      mortality in the paediatric age group in many developing countries. The main
      objective of this study was to review the mortality in HIV-infected paediatric
      patients in Barbados. It is a retrospective analysis of the hospitalization
      course of HIV-infected paediatric patients aged < 16 years who died during a 15
      year period of surveillance. Using a specific database, information pertaining to
      number and duration of hospitalizations, and cause of death were analyzed. There
      were 39 (65%) deaths among 60 HIV-infected patients diagnosed during the period
      of study. Twenty-one (54%) were male and 18 (46%) were female. Twenty-seven (69%)
      case records were retrieved for analysis. The highest mortality (56%) was among
      patients aged < 1 year and between 1989 and 1995. Hospitalizations averaged three
      per patient. No patient received anti-retroviral therapy. Nineteen (70%) patients
      died during hospitalization on the paediatric ward. Lower respiratory tract
      infections suspected to be Pneumocystis carinii, gastroenteritis and septicaemia
      were the most frequent diagnoses at the time of death. The annual mortality
      ranged between 0 and 1.7 (mean 0.7) per 1000 live births. The overall mortality
      rate was high among HIV-infected paediatric patients, with lower respiratory
      tract infections being implicated as a major contributing cause of death. Results
      of this study definitely indicate a need for improved resources in the management
      of paediatric HIV/AIDS cases, especially focussing on the availability and
      administration of anti-retroviral therapy.

PMID- 12806751
TI  - Relationship of sexuality with psychological and hormonal features in the
      menopausal period.
AB  - Women may experience some mental and sexual problems between the ages of 40 years
      and 60 years due to serious changes in the hormonal system. The aim of this study
      was to examine the relationships between the changes in sex hormones, sexual
      behaviours, depression and anxiety levels of women who were in either the
      premenopausal, perimenopausal or postmenopausal period. The subjects of this
      cross-sectional study consisted of 324 women who attended the Gynaecology and
      Obstetrics Out-Patient Ward of Celal Bayar University Hospital. Of this group,
      37.0% (n = 124) were postmenopausal, 27.2% (n = 84) perimenopausal and 35.8% (n =
      116) premenopausal. Beck Depression Inventory (BDI), State and Trait Anxiety
      Inventories (STAI-I and II) and a questionnaire on sexual behaviour which was
      prepared for this study by the authors, were applied to all of the attendees and
      serum sex hormone levels were analyzed. Beck Depression Anxiety, STAI-I and STAI
      II scores and sexual behaviours did not show any statistically significant
      difference among these three groups. The frequency of sexual intercourse was
      lower in women with high BDI scores. The rate of painful intercourse was higher
      in women with high STAI-I scores. The frequency of sexual intercourse, sexual
      desire and orgasm decreased and painful intercourse increased in women with high
      STAI-II scores. The frequency of sexual intercourse decreased significantly as
      the age or follicle stimulating hormone level of women increased. These findings
      have revealed that the menopausal state did not affect the sexual behaviour, and
      psychological state of women between the ages of 40 and 60 years, but the
      increase in anxiety and depression scores affected the sexual life in a negative
      manner.

PMID- 12806752
TI  - Extended-spectrum beta-lactamase producing enterobacteriaceae in a tertiary care
      hospital in Trinidad and Tobago.
AB  - Extended-spectrum beta-lactamase (ESBL) mediated resistance to third generation
      cephalosporins, amongst the family Enterobacteriaceae, is emerging worldwide.
      This is the Caribbean's first survey on ESBL production, and was conducted during
      two six-month periods in 1998 and 2001, in a tertiary health institution in
      Trinidad and Tobago. Consecutive ampicillin resistant isolates of the family
      Enterobacteriaceae from in-patients were screened for resistance to third
      generation cephalosporins, and for ESBL production. The proportion of isolates
      found to be ESBL producers was similar in both samples (40 of 560 and 23 of 361).
      Overall, ESBL production was more frequent in enterobacter, citrobacter and
      proteus (and related organisms) than in Klebsiella and Escherichia (11.2% and
      4.6%, respectively, p < 0.001). In the 1998 sample, this proportion (9.8% versus
      5.8%) was significant (p < 0.05), but the difference was more marked in the 2001
      sample (13.6% versus 2.9%, p < 0.001). Continued distribution of these resistant
      bacterial strains is of concern. In the Caribbean region, more laboratory
      surveillance and increased infection control vigilance are recommended, with
      focus on specific genera in the family.

PMID- 12806753
TI  - Utility of rapid staining of fine needle aspiration smears at the University
      Hospital of the West Indies.
AB  - In a prospective study at the University Hospital of the West Indies, 187 fine
      needle aspiration cytology (FNAC) specimens, comprising 100 breast, 75 head and
      neck, and 12 miscellaneous specimens, were subjected to rapid Papanicolaou
      staining and immediate assessment. Inadequate aspirates were repeated, and all
      cases were also evaluated after routine Papanicolaou staining. Histologic and
      clinical follow-up data were obtained. The overall concordance between rapid and
      routine cytologic diagnoses ranged from 79% to 87% for the three specimen
      cohorts. Sensitivity and specificity values were similar for rapid and routine
      stained slides and ranged from 80% to 100%. There were no false positive or false
      negative diagnoses in the cases for which the outcome was known. Rapid staining
      of cytologic smears is a useful adjunct to the evaluation of aspirated material,
      improving adequacy rates and overall performance of the FNAC service, and should
      also result in significant savings in time and cost to patients.

PMID- 12806754
TI  - Hepatic abscesses at the University Hospital of the West Indies. A 24-year
      autopsy review.
AB  - A retrospective review of all hepatic abscesses identified at autopsy over the 24
      year period 1977-2000 at the University Hospital of the West Indies (UHWI),
      Kingston, Jamaica, was conducted. Post mortem and microbiology records were
      reviewed. Data collected included age, gender, predisposing factors, organisms
      isolated, number of abscesses and associated conditions, such as diabetes
      mellitus. Data for the adults was analyzed separately. Thirty-nine cases of
      pyogenic abscesses were identified from 7480 post-mortems. Thirty-three occurred
      in adults of mean age 59.5 years. Sixty per cent of the abscesses were solitary.
      Biliary tract disease was the predisposing factor in 33% of cases. Six per cent
      were cryptogenic: 11/33 patients were diabetic and these were significantly older
      than non-diabetics (p < 0.014) Klebsiella pneumoniae was the most common organism
      isolated from diabetics (6.9). Only 2/33 abscesses were diagnosed ante-mortem.
      The abscesses in children were more frequently multiple and associated with extra
      abdominal infection. Gram positive cocci were the commonly isolated organisms in
      children. There were no cases of amoebic abscess. The prevalence of hepatic
      abscess was low. Diabetes mellitus was a significant contributing factor. A high
      index of clinical suspicion is therefore warranted particularly in elderly
      diabetics.

PMID- 12806755
TI  - Heart weight and heart weight/body weight ratio in a Jamaican adult autopsy
      population. A preliminary study.
AB  - The heart weight and heart weight/body weight (HW/BW) ratio were assessed in an
      adult autopsy population and compared with commonly used reference values.
      Examination of 127 adult post-mortem cases (80 males and 47 females, aged 17 to
      91 years) revealed that the mean heart weight and the HW/BW ratios of both
      genders were significantly greater than the reference values, particularly so in
      the hypertensive patients. These findings suggest that the Jamaican adult heart
      is significantly heavier than values used from reference tables. In both genders,
      heart weight was significantly and positively correlated with body weight and
      body mass index but not height, for non-hypertensive and hypertensive subjects.
      The present data are preliminary and not comprehensive enough to establish
      definitive reference values for the Jamaican population. However, this
      information needs to be taken into consideration when making pathologic diagnoses
      using heart weight as a criterion in post-mortem diagnosis.

PMID- 12806756
TI  - Improving medical undergraduate trauma education through the Trauma Evaluation
      and Management programme at Mona.
AB  - This study examines the potential role of the Trauma Evaluation and Management
      (TEAM) programme in the undergraduate curriculum for medical students in Jamaica.
      Thirty-two final year medical students were randomly assigned to two groups of
      16. One group (No TEAM) completed two 20-item multiple choice question (MCQ)
      examinations on trauma resuscitation topics. The second group (TEAM group)
      completed the first 20-item MCQ. The TEAM manual was then distributed to both
      groups. After the TEAM programme for both groups, the TEAM group had the second
      MCQ examination. Unpaired "t" tests were used for in-between group and paired "t"
      tests for between group comparisons with p < 0.05 being considered statistically
      significant. Both groups completed a post-course questionnaire rating five items
      on a scale of one to five. The No TEAM group showed no difference in mean scores
      between the 1st and 2nd tests (55.3% in the 1st test to 52.2% in the 2nd test, p
      = 0.32). The TEAM Group improved their MCQ scores from 53.1% pre-module to 69.4%
      post-module (p < 0.001). A score of four of five was assigned by 28 students for
      the statement that the objectives were met, that trauma knowledge was improved
      and that there was overall satisfaction; by 17 students that clinical trauma
      skills were improved and 29 students that TEAM should be mandatory in the
      undergraduate curriculum. The TEAM programme improved trauma knowledge skills
      among senior medical students in Jamaica. The questionnaire results suggested
      enthusiasm for the programme and that it be made mandatory in the senior
      undergraduate medical curriculum.

PMID- 12806757
TI  - Whither medical Marijuana?

PMID- 12806758
TI  - Image and diagnosis. Lipoma.

PMID- 12806759
TI  - Acute haematogenous anaerobic osteomyelitis in sickle cell disease. A case report
      and review of the literature.
AB  - Patients with sickle cell disease are more susceptible to acute anaerobic
      osteomyelitis due to focal gut mucosal ischaemia, translocation of bacteria, and
      seeding in infarcted bone marrow. Modulation of the immune system is also
      present. The isolation of anaerobic organisms requires a high index of suspicion,
      correct specimen collection procedures and meticulous specimen handling.
      Bacteroides is the predominant organism isolated. Intra-osseous gas in the bone
      may be seen within four days and radiographs are therefore useful earlier than
      with aerobic osteomyelitis. Surgical debridement and intravenous antibiotics are
      the mainstay of treatment with the erythrocyte sedimentation rate being relied on
      heavily to guide conversion to oral antibiotics. Coexistence of septic arthritis
      is more common with anaerobic osteomyelitis.

PMID- 12806760
TI  - Severe refractory sarcoidosis in a 64-year-old man with persistent leucopenia.
AB  - We present a case of bone marrow granulomas in a 64-year-old West Indian man who
      presented with severe leucopenia, anaemia, thrombocytopenia, hepatosplenomegaly,
      hypercalcaemia, hypercalciuria, elevated angiotensin converting enzyme level and
      reticulo-nodular shadows on chest X-ray. Bone marrow biopsy revealed numerous non
      caseating epithelioid granulomas. A diagnosis of sarcoidosis was made and he was
      treated with prednisolone 60 mg daily for four weeks and the dose was
      subsequently reduced to 30 mg daily. Eight months follow-up revealed persistent
      pancytopenia. Bone marrow granulomas are rare and, when they occur, sarcoidosis
      is an uncommon aetiology. This case illustrates that severe leucopenia may occur
      in sarcoidosis and may present therapeutic difficulties.

PMID- 12806761
TI  - Rivastigmine in the treatment of alcohol-induced persisting dementia.
AB  - A case of Alcohol-Induced Persisting Dementia (AIPD) in a 62-year-old man is
      presented. His progress on treatment with the acetylcholinesterase inhibitor,
      rivastigmine, is followed. The significant improvement observed suggests that
      AIPD may be a new indication for this class of drug.

PMID- 12806762
TI  - Successful pregnancy and delivery after pulmonary autograft operation (Ross
      procedure) for rheumatic aortic valve insufficiency.
AB  - A young woman with aortic valve insufficiency secondary to rheumatic heart
      disease underwent replacement of her diseased aortic valve with her own pulmonary
      valve and replacement of her pulmonary valve with an aortic cadaver homograft,
      the Ross procedure. She went on to conceive and deliver a normal infant. The Ross
      procedure is the operation of choice in a young woman with aortic valve disease,
      since it avoids anti-coagulation fetal loss, valve deterioration and other
      maternal risk from pregnancy associated with other valve replacement options.

PMID- 12806763
TI  - A case report of post-traumatic facial reconstruction in the West Indies.
AB  - The radial forearm free flap is one of the most commonly used free flaps in
      reconstructive surgery. It is a recognized option for facial reconstruction
      internationally, but, to our knowledge, it has not been widely used in the
      Caribbean. We present a patient who posed a difficult reconstructive problem, for
      which the radial forearm free flap was the ideal solution, utilizing the flap's
      features of a long length of pedicle, large area of coverage, minimal tissue
      bulk, and options for further cosmetic revision.

PMID- 12806764
TI  - Latissimus dorsi muscle flap based on arterial branch to serratus anterior as
      salvage of a failed bipedicled transverse rectus abdominis muscle flap. A case
      report.
AB  - We present a case of a failed bipedicled (unilateral rectus flap with superior
      epigastric pedicle preserved and inferior epigastric vessels anastomosed to the
      thoracodorsal trunk as the second pedicle) transverse rectus abdominis muscle
      flap that had compromised the dominant pedicle of the latissimus dorsi muscle. A
      salvage procedure was possible using this muscle as a pedicle flap based on the
      back-flow from the serratus anterior arterial branch with success. The use of the
      reconstructive ladder is highlighted.

PMID- 12806765
TI  - Colloquium for Donald Edward Christian.

PMID- 12806769
TI  - Acute subdural haematoma without subarachnoid haemorrhage caused by rupture of an
      intracranial aneurysm.

PMID- 12806770
TI  - Light-dark regulation of carotenoid biosynthesis in pepper (Capsicum annuum)
      leaves.
AB  - The carotenoid content in photosynthetic plant tissue reflects a steady state
      value resulting from permanent biosynthesis and concurrent photo-oxidation. The
      contributions of both reactions were determined in illuminated pepper leaves. The
      amount of carotenoids provided by biosynthesis were quantified by the
      accumulation of the colourless carotenoid phytoene in the presence of the
      inhibitor norflurazon. When applied, substantial amounts of this rather photo
      stable intermediate were formed in the light. However, carotenoid biosynthesis
      was completely stalled in darkness. This switch off in the absence of light is
      related to the presence of very low messenger levels of the phytoene synthase
      gene, psy and the phytoene desaturase gene, pds. Other carotenogenic genes, such
      as zds, ptox and Icy-b also were shown to be down-regulated to some extent. By
      comparison of the carotenoid concentration before and after transfer of plants to
      increasing light intensities and accounting for the contribution of biosynthesis,
      the rate of photo-oxidation was estimated for pepper leaves. It could be
      demonstrated that light-independent degradation or conversion of carotenoids e.g.
      to abscisic acid is a minor process.

PMID- 12806771
TI  - Kinetic behavior of the Arabidopsis thaliana leaf formate dehydrogenase is
      thermally sensitive.
AB  - Two previous kinetic studies on the Arabidopsis thaliana leaf NAD-dependent
      formate dehydrogenase (EC 1.2.1.2) have demonstrated two very different sets of
      Km values for the formate and NAD+ substrates. We examined the kinetics of the
      enzyme partially purified from a leaf extract by gel-filtration desalting and
      chromatography on DEAE-cellulose, as well as by isolation of a mitochondria
      enriched fraction obtained by differential centrifugation. Both of these methods
      produce a formate dehydrogenase enzyme with the higher Km values of approximately
      10 mmol/L formate and 75 mumol/L NAD+. The kinetic properties of the Arabidopsis
      formate dehydrogenase expressed to high levels in transgenic tobacco plants were
      also those of the high Km form. The high Km form of the enzyme converted to a low
      Km form by heating for 5 minutes at 60 degrees C. An Arrhenius plot of the
      activity during the heating process was linear, indicating that the heating did
      not cause alterations in either the active site or the thermal dependence of the
      catalytic reaction. We conclude that the native form of the formate dehydrogenase
      probably resembles the form with the higher Km values. Heating seemingly converts
      this native enzyme to the molten globule state and cooling results in formation
      of a non-native structure with altered kinetic properties.

PMID- 12806772
TI  - Carotenoid levels during the period of growth and ripening in fruits of different
      olive varieties (Hojiblanca, Picual and Arbequina).
AB  - During fruit growth and development, carotenoid accumulation follows the same
      qualitative pattern in three olive varieties (Olea europaea L.). In the stage of
      ripening, the Arbequina variety is differentiated from Hojiblanca and Picual by
      its possession of esterified xanthophylls. The Chl a/b ratio is higher in
      Arbequina than in Hojiblanca and Picual throughout the life cycle of the fruit,
      while the percentage of lutein is always lower, and that of beta-carotene higher.
      Independent of the high (Hojiblanca and Picual) or low (Arbequina) pigment
      content, the chlorophyll/carotenoid ratio (a + b)/(x + c) is similar for the
      three varieties. There is evident carotenoid breakdown at the onset of ripening
      in the fruits of the Hojiblanca and Picual varieties, while in Arbequina there is
      a new period of carotenoid accumulation. As ripening proceeds in Arbequina
      fruits, a slow carotenoid-breakdown process is initiated.

PMID- 12806773
TI  - The metabolic pathway of salicylic acid rather than of chlorogenic acid is
      involved in the stress-induced flowering of Pharbitis nil.
AB  - We examined the involvement of chlorogenic acid (CGA) and salicylic acid (SA) in
      the stress-induced flowering of Pharbitis nil (synonym Ipomoea nil). The
      incorporation efficiency of exogenously applied CGA and the deactivation rate of
      incorporated CGA were determined in cotyledons by high-performance liquid
      chromatography. The assay plants could not incorporate a sufficient amount of CGA
      via roots. The perfusion technique by which the assay solution was forced into
      the plant from the cut end of the hypocotyl improved the efficiency of CGA
      incorporation. However, no flower-inducing activity was detected, indicating that
      CGA was not involved in flowering. It was concluded that the close correlation
      between CGA content and flowering response is merely coincidence or a
      parallelism. Flowering under long-day conditions induced by low-temperature
      stress was completely inhibited by aminooxyacetic acid (AOA), an inhibitor of
      phenylalanine ammonialyase. The flower-inhibiting effect of AOA was nullified by
      co-applied t-cinnamic acid and by benzoic acid. This indicates that the metabolic
      pathway from t-cinnamic acid to SA via benzoic acid is involved in the stress
      induced flowering. The results indicate that the metabolic pathway of SA is
      involved in the stress-induced flowering of P. nil not the metabolic pathway of
      CGA.

PMID- 12806774
TI  - Distribution of activated calmodulin in the chloronema tip cells of the moss
      Funaria hygrometrica.
AB  - Auxin (indole-3-acetic acid) regulates caulonema differentiation as a result of
      gradual transitional events in the chloronema tip cells in moss protonema. This
      auxin action in the moss Funaria hygrometrica involves a rapid influx of calcium
      ions from the extracellular medium. This investigation demonstrates spatial and
      temporal changes in calmodulin (CaM) activation (formation of Ca(2+)-CaM complex)
      in the chloronema tip cells subjected to auxin treatment. Photomicroscopic
      localisation of the fluorescence (excitation at 365 nm and emission of 397 nm)
      from the tricomplex of Ca(2+)-CaM with trifluoperazine (TFP, a blocker of Ca(2+)
      CaM action) shows a tip to base (tip high) gradient of Ca(2+)-CaM in the
      chloronema tip cells. Comparison of Ca(2+)-CaM-TFP fluorescence over time in the
      chloronema tip cells of wild type Funaria with the response in an auxin
      overproducer mutant (86.1) and an auxin deficient mutant (87.13) reveals the
      involvement of auxin in calmodulin activation as a rapid response prior to cell
      differentiation.

PMID- 12806775
TI  - Abscisic acid-induced freezing tolerance in the moss Physcomitrella patens is
      accompanied by increased expression of stress-related genes.
AB  - Abscisic acid (ABA)-induced genes are implicated in the development of freezing
      tolerance during cold acclimation in higher plants, but their roles in lower land
      plants have not been determined. We examined ABA- and cold-induced changes in
      freezing tolerance and gene expression in the moss Physcomitrella patens. Slow
      equilibrium freezing to -4 degrees C of P. patens protonemata grown under normal
      growth conditions killed more than 90% of the cells, indicating that the
      protonema cells are freezing-sensitive. ABA treatment for 24 h dramatically
      increased the freezing tolerance of the protonemata, while cold treatment only
      slightly increased the freezing tolerance within the same period. We examined the
      expressions of fourteen Physcomitrella patens ABA-responsive genes (PPARs),
      isolated from ABA-treated protonemata. ABA treatment resulted in a remarkable
      increase in the expression of all the PPAR genes within 24 h. Several of the PPAR
      genes (PPAR 1 to 8, and 14) were also responsive to cold, but the response was
      much slower than that to ABA. Treatment with hyperosmotic concentrations of NaCl
      and mannitol increased freezing tolerance of protonemata and also increased the
      expression levels of eleven PPAR genes (PPAR2, 3, 5 to 8, and 10 to 14). These
      results suggest that ABA and environmental stresses positively affect the
      expression of common genes that participate in protection of protonema cells
      leading to the development of freezing tolerance.

PMID- 12806776
TI  - Photosynthetic responses of corn and soybean to foliar application of
      salicylates.
AB  - Salicylic acid (SA) and related phenolic compounds can exert control over
      stomatal opening and previous work in our laboratory has shown that chronic
      injection of SA increases the photosynthetic rate of corn. The work reported in
      this paper investigated the effects of foliar applied SA, acetyl salicylic acid
      (ASA) and gentisic acid (GTA) on photosynthetic rates and growth of soybean (a C3
      plant) and corn (a C4 plant) under greenhouse conditions. In general, the tested
      compounds enhanced photosynthetic rates in both soybean and corn. Stomatal
      conductance and transpiration were also increased. These compounds do not alter
      chlorophyll content. In some cases treatment with these compounds resulted in
      increased leaf areas and plant dry mass, however, plant height and root length
      were not affected.

PMID- 12806777
TI  - Two potential Ca(2+)-mobilizing processes depend on the abscisic acid
      concentration and growth temperature in the Arabidopsis stomatal guard cell.
AB  - The abscisic acid (ABA) stomatal closing signal might be transduced through
      different pathways, depending on the plant growth temperature (GT) and the
      applied ABA concentration. This was investigated in epidermal peels of
      Arabidopsis thaliana (L.) Columbia. Different Ca2+ buffers and guanosine
      triphosphate-binding protein (G protein) modulators were tested on stomatal
      closing under light in response to 3 mumol/L ABA (ABA3 mu) and 30 mumol/L ABA
      (ABA30 mu) at the 15-17 degrees C and 23-25 degrees C GT ranges. The Ca2+ buffer,
      1,2-bis(0-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, used as free acid
      (BAPTA) or acetoxymethyl ester (BAPTA-AM), similarly inhibited (up to
      approximately 70% inhibition) stomatal closing to ABA3 mu and ABA30 mu, whereas
      ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
      specifically inhibited (up to approximately 70% inhibition) the ABA3 mu response
      at the 23-25 degrees C GT range. At the same GT range, the ABA3 mu response was
      specifically affected by the phospholipase C (PLC) inhibitor 1-[6-[[17 beta-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122).
      Moreover, the ABA30 mu response was specifically inhibited by the G protein
      antagonist pGlu-Gln-D-Trp-Phe-D-Trp-D-Trp-Met-NH2 (GP Ant-2) and by the inactive
      mastoparan analog, mas 17. The inhibitory effects of GP Ant-2 and mas 17 were
      additive. None of the tested pharmacological compounds were effective at the 15
      17 degrees C GT range. Together, these results confirmed that, depending on GT
      and the exogenous ABA concentration, stomatal closing to ABA involves either one
      among two Ca2+ mobilizations or none of them.

PMID- 12806778
TI  - The promoter of the spinach PsaF gene for the subunit III of the photosystem I
      reaction center directs beta-glucuronidase gene expression in transgenic tobacco
      roots. Implication of the involvement of phospholipases and protein kinase C in
      PsaF gene expression.
AB  - PsaF is a nuclear encoded gene for the subunit III of photosystem I. It is
      located at the lumenal side of the thylakoid membrane and interacts with
      plastocyanin. Starting from a low-level expression in the cotyledons of etiolated
      seedlings the gene is upregulated by light. Light can be replaced by Ca2+ or
      phosphoinositides like phorbol myristate acetate, an analogue of diacylglycerol.
      We tested the effects of these components on PsaF promoter-driven gene expression
      in roots and found that the PsaF promoter includes a positive regulatory region [
      220/-179] activated by cytokinin and a negative regulatory region [-687/-221]
      activated by abscisic acid. In addition, the promoter is activated by Ca2+,
      mastoparan and phorbol myristate acetate which suggests a role for phospholipases
      and protein kinase C in PsaF gene expression.

PMID- 12806779
TI  - Different responses of tobacco antioxidant enzymes to light and chilling stress.
AB  - The effect of elevated light treatment (25 degrees C, PPFD 360 mumol m-2 sec-1)
      or chilling temperatures combined with elevated light (5 degrees C, PPFD 360
      mumol m-2 sec-1) on the activity of six antioxidant enzymes, guaiacol
      peroxidases, and glutathione peroxidase (GPx, EC 1.11.1.9) protein accumulation
      were studied in tobacco Nicotiana tabacum cv. Petit Havana SR1. Both treatments
      caused no photooxidative damage, but chilling caused a transient wilting. The
      light treatment increased the activities of ascorbate peroxidase (APx, EC
      1.11.1.11) and guaiacol peroxidases while catalase (EC 1.11.1.6), superoxide
      dismutase (SOD, EC 1.15.1.1), monodehydroascorbate reductase (MDHAR, EC 1.6.5.4),
      dehydroascorbate reductase (DHAR, EC 1.8.5.1), and glutathione reductase (EC
      1.6.4.2) were unchanged. In contrast, chilling treatment did not increase any of
      the antioxidant enzyme activities, but decreased catalase and to a lesser extent
      DHAR activities. Glutathione peroxidase protein levels increased sporadically
      under light treatment and constantly under chilling. Both chilling and light
      stress caused induction of glutathione synthesis and accumulation of oxidised
      glutathione, although the predominant part of the glutathione pool remained in
      the reduced form. Antioxidant enzymes from the chilling treated plants were
      measured at both 25 degrees C and 5 degrees C. Measurements at 5 degrees C
      revealed a 3-fold reduction in catalase activity, compared with that measured at
      25 degrees C, indicating that the overall reduction in catalase after four days
      of chilling was approximately 10-fold. The overall reduction in activity for the
      other antioxidant enzymes after four days of chilling was 2-fold for GR and APx,
      1.5-fold for MDHAR, 3.5-fold for DHAR. The activity of SOD was the same at 25 and
      5 degrees C. These results indicate that catalase and DHAR are most strongly
      affected by the chilling treatment and may be the rate-limiting factor of the
      antioxidant system at low temperatures.

PMID- 12806780
TI  - Elongation growth in leaf blades of Chloris gayana under saline conditions.
AB  - In Chloris gayana, salinity-associated yield decreases are due mainly to leaf
      area reductions. To understand the physiological basis for such reduction, the
      effects of salinity were studied on the spatial and temporal distribution of
      extension in the intercalary meristem at the leaf base, and on hydraulic
      conductance in that zone. C. gayana plants were grown on sand irrigated with
      Hoagland solution with the addition of 0 or 200 mmol/L NaCl, and all measurements
      were performed on tiller leaf four. In salinised plants, that leaf was 20%
      shorter than in controls. Extension in the blade expansion zone was studied by
      pricking through the leaf sheaths and analysing the displacement of the pricks.
      In salt-treated plants, maximum growth rates were depressed by 53% and the growth
      zone was shorter by approximately 10 mm, nevertheless, extension proceeded for a
      longer period than in control plants. The analysis of specific leaf areas in the
      expansion zone suggests the rate of dry matter deposition was lowered by salinity
      and estimations of tissue displacement time within that zone suggest cell wall
      maturity was delayed. Hydraulic conductance was reduced by salinity and this may
      be the main cause for reduced growth under salinity in Chloris gayana.

PMID- 12806781
TI  - Nitrate transport across the tonoplast of Cucumis sativus L. root cells.
AB  - Nitrate transport across the tonoplast has been studied using vacuole membranes
      isolated from cucumber roots grown in nitrate. The addition of NO3- ions into the
      tonoplast with ATP-generated transmembrane proton gradient caused the dissipation
      of delta pH, indicating the NO3(-)-induced proton efflux from vesicles. NO3(-)
      dependent H+ efflux was almost insensitive to the transmembrane electrical
      potential difference, suggesting the presence of an electroneutral NO3-/H+
      antiporter in the tonoplast. Apart from saturation kinetics, with respect to
      nitrate ions, NO3(-)-linked H+ efflux from the tonoplast of cucumber roots showed
      other characteristics expected of substrate-specific transporters. Experiments
      employing protein modifying reagents (NEM, pCMBS, PGO and SITS) indicated that a
      crucial role in the activity of tonoplast nitrate/proton antiporter is played by
      lysine residues (strong inhibition of NO3-/H+ antiport by SITS). None of the ion
      channel inhibitors (NIF, ZnSO4 and TEA-Cl) used in the experiments had a direct
      effect on the nitrate transport into tonoplast membranes. On the other hand,
      every protein reagent, as well as NIF and ZnSO4, significantly affected the ATP
      dependent proton transport in vesicles. Only TEA-Cl, the potassium channel
      blocker, had no effect on the vacuolar proton pumping activity.

PMID- 12806782
TI  - Source-sink manipulations suggest an N-feedback mechanism for the drop in N2
      fixation during pod-filling in pea and broad bean.
AB  - Various legume species show a marked decline in N2 fixation during pod-filling.
      The objective of this study was to clarify whether this is a result of impaired
      nodule assimilate supply or whether re-moblised N from senescing lower leaves
      initiates the phenomenon through an N-feedback impact. In model experiments on
      pea and broad bean plants during vegetative and reproductive growth, 30 or 60% of
      green leaves were either excised or individually darkened, thus removing the same
      photosynthetic capacity yet allowing N to be re-mobilised from darkened leaves.
      Results are consistent with an N-feedback down-regulation of nitrogenase in that
      1. leaf darkening reduced N2 fixation to a greater extent then excision, 2.
      darkened leaves quickly senesced and N from these leaves was re-mobilised in
      substantial amounts, 3. N and amino acids (AA) accumulated and C/N ratios
      decreased in nodules of plants with darkened leaves versus excision or untreated
      controls. These findings further support various indirect evidence that
      nitrogenase is regulated by an N-feedback mechanism that is not yet fully
      understood.

PMID- 12806783
TI  - A transfer of carbon atoms from fatty acids to sugars and amino acids in yellow
      lupine (Lupinus luteus L.) seedlings.
AB  - The metabolism of 14C-acetate was investigated during the in vitro germination of
      yellow lupine seeds. Carbon atoms (14C) from the C-2 position of acetate were
      incorporated mainly into amino acids: aspartate, glutamate, and glutamine and
      into sugars: glucose, sucrose, and fructose. In contrast to this, 14C from the C
      1 position of acetate was released mainly as 14CO2. Incorporation of 1-14C and 2
      14C from acetate into amino acids and sugars in seedling axes was more intense
      when sucrose was added to the medium. However, in cotyledons where lipids are
      converted to carbohydrates, this process was inhibited by exogenous sucrose.
      Since acetate is the product of fatty acid beta-oxidation, our results indicate
      that, at least in lupine, seed storage lipids can be converted not only to
      sucrose, but mainly to amino acids. Inhibitory effects of sucrose on the
      incorporation of 14C from acetate into amino acids and sugars in cotyledons of
      lupine seedlings may be explained as the effect of regulation of the glyoxylate
      cycle by sugars.

PMID- 12806784
TI  - Molecular cloning of two metallothionein-like protein genes with differential
      expression patterns from sweet potato (Ipomoea batatas) leaves.
AB  - Metallothionein (MT) is a group of proteins with low molecular masses and high
      cysteine contents, and is classified into different types, which in general
      contains two domains (domain 1 and domain 2) with typical amino acid sequences
      (Rauser 1999). In this report two full-length cDNAs (Y459 and G14) encoding MT
      like proteins were isolated from leaves of sweet potato (Ipomoea batatas). Their
      open reading frames contained 249 and 195 nucleotides (82 and 64 amino acids) for
      Y459 and G14, respectively, and exhibited a relatively low amino acid sequence
      similarity (ca. 25.8%). Gene structure studies showed that Y459 had the conserved
      domain 1 region of type 2 MT; however, the domain 2 region was not conserved and
      contained additional amino acids between the CxC and CxC spacing. G14 had
      conserved domains 1 and 2 of type 4 MT except that the last CxC of domain 2 was
      changed to RxC. Semi-quantitative RT-PCR showed that Y459 was expressed in
      significant quantity in roots and stems, but was much less in green leaves.
      During natural and induced (with dark and ethephon, an ethylene-releasing
      compound, treatments) leaf senescence, Y459 gene expression was significantly
      enhanced. In contrast, relatively constant gene expression levels were found for
      G14 in all tissues or treatments analyzed. In conclusion, the two MT-like protein
      genes of sweet potato display differential gene structures and gene expression
      patterns, which may be associated with the diverse roles and functions they play
      in plant physiology in order to cope with particular developmental and
      environmental cues.

PMID- 12806785
TI  - An efficient protocol for the production of triploid plants from endosperm callus
      of neem, Azadirachta indica A. Juss.
AB  - Triploid plants of neem were obtained by immature endosperm culture. Immature
      seeds, at the early dicotyledonous stage of embryo development, is the best
      explant to raise endosperm callus on MS + NAA (5 mumol/L) + BAP (2 mumol/L) + CH
      (500 mg L-1). Maximum shoot bud differentiation from the endosperm callus
      occurred on MS + 5 mumol/L BAP. Shoots were multiplied by forced axillary
      branching and rooted in vitro. The plants were established in soil. Over 66% of
      the plants were triploid with chromosome number 2n = 3x = 36. A characteristic
      feature of the shoots of endosperm origin is the presence of a large number of
      multi-cellular glands.

PMID- 12806786
TI  - Anoxia tolerance in rice roots acclimated by several different periods of
      hypoxia.
AB  - Rice (Oryza sativa L.) seedlings were subjected to hypoxic pretreatment (H-PT;
      incubated in 5% O2 atmosphere) for various lengths of time followed by an anoxic
      stress. Anoxia tolerance of rice roots was improved with increasing duration of H
      PT, but longer H-PT than 12 h gave no additional improvement. Concentrations of
      ATP and ethanol, and activities of pyruvate decarboxylase (EC 4.1.1.1) and
      alcohol dehydrogenase (EC 1.1.1.1) in the roots were increased by H-PT, and the
      times and patterns of increasing in these concentrations and activities were
      similar to those of increasing in the anoxia tolerance. These results suggest
      that the H-PT may increase anoxia tolerance due to maintenance of ATP levels with
      rapid induction of ethanolic fermentation, and hypoxic acclimation may occur
      within 12 h.

PMID- 12806787
TI  - Regulatory role of iron and EDTA in the shoot development from the epicotyl
      explants of Syzygium cuminii.
AB  - Iron has proved to be an integral component of the culture medium supporting the
      caulogenic response of the epicotyl segments of S. cuminii. In the absence of
      both the iron and EDTA even the shoot buds failed to develop, while in the
      presence of either of these, though the shoot buds developed, their elongation
      was adversely affected. Among the three iron sources tested, ferrous sulphate
      proved to be the best, as the ferric chloride was not as effective as the former
      when used either alone or along with EDTA. Ferric citrate, on the other hand,
      when provided alone, elicited better response than that induced by ferrous
      sulphate alone. However, in combination with EDTA, the response declined
      significantly. The estimation of endogenous levels of iron in the explants
      further supported these results. The quantum of iron absorption was at a maximum
      during the first week of the culture and the explants, once deprived of iron
      during the first week, failed to catch up to the level of iron accumulated in the
      explants maintained continuously on complete medium, even after transfer to the
      complete medium. Likewise, the level of copper ions did not come up to comparable
      levels even if the explants were transferred to the complete medium after initial
      deprivation.

PMID- 12806788
TI  - Differential effect of NaCl and polyethylene glycol on the ultrastructure of
      chloroplasts in rice seedlings.
AB  - Ionic and osmotic effects of salinity on the ultrastructure of chloroplasts in
      salt-treated rice seedlings were investigated. After rice seedlings were grown in
      hydroponic culture for three weeks, they were treated with NaCl and polyethylene
      glycol (PEG) 4000 both at a water potential of -1.0 MPa for 3 days. The most
      notable difference in ultrastructural change between NaCl and PEG treatment was
      observed in the damage in chloroplast membranes. NaCl induced swelling of
      thylakoids and caused only a slight destruction of the chloroplast envelope. PEG
      caused severe destruction of the chloroplast envelope compared with NaCl, however
      thylakoids did not swell. Our observations suggested that in salt-treated rice
      plants, the ionic effects induced swelling of thylakoids and the osmotic effects
      caused the destruction of chloroplast envelope.

PMID- 12806789
TI  - Perceptions of a required hospice experience: a comparison of first- and fourth
      year medical students.
AB  - As more attention is focused on the need to improve end-of-life care, medical
      schools are expanding curricula in this area. This paper presents information
      about a 12-week, 60-hour hospice unit required for first-year medical students
      between 1989 and 2001, along with a comparison of first- and fourth-year
      students' perceptions of this unit. Surveyed in summer of 2001 were 111
      individuals who had completed the unit: 59 students who had completed the hospice
      unit in the 2000-01 academic year and 52 graduating students who had completed
      the hospice unit in the 1997-98 academic year. The survey tapped perceptions of
      usefulness of the unit, comfort with end-of-life-care knowledge and skills, and
      suggestions for improvement. Ninety percent of graduating students rated the
      hospice experience as personally valuable and 81% aceeded its important for
      medical education, compared to 69% and 65% of first-year students, respectively.
      Almost all felt that the hospice unit was a useful experience for them as future
      clinicians. However, there were few differences in comfort with end-of-life
      skills between the two classes, e.g., almost 90% felt comfortable listening to
      patients; about 50% felt comfortable with their knowledge of grief/bereavement,
      symptom control, physical needs and psychosocial needs; and only 25% felt
      comfortable discussing a patient's terminal illness with the patient and family.
      The majority of students felt the unit should remain a first-year requirement,
      but wanted more opportunities to attend dying patients, work with physician role
      models, and reflect on their experience with death and its meaning.

PMID- 12806790
TI  - Metformin induced anorexia and weight loss.

PMID- 12806791
TI  - Tobacco reduction advocacy and education for Hawaii's physicians-in-training.

PMID- 12806792
TI  - Radiation oncology update.
AB  - Recent technological developments in radiation oncology, enabled by high-speed
      computers, are allowing better target localization, faster throughput and more
      confined treatment delivery. Although available in only certain locations and
      beneficial for only selected cases, Intensity Modulated Radiation Therapy (IMRT)
      and Stereotactic Radiosurgery (SRS) represent exciting and revolutionary
      techniques of providing more concise doses of radiation to specifically targeted
      volumes while minimizing radiation to surrounding non-target tissues. IMRT and
      SRS, therefore, theoretically can improve control rates while lowering toxicity
      of radiation treatment. While the technology is less expensive and less
      logistically challenging than machines for neutron and proton delivery, increased
      time for treatment planning and quality assurance, financial feasibility and cost
      effectiveness remain significant issues and have therefore limited more
      widespread application. Research continues on the use of chemotherapy and
      biologic modifiers to alter cell sensitivity to radiation, decrease side effects,
      and improve the therapeutic ratio. Potential applications are expanding for use
      of brachytherapy to prevent restenosis and in the treatment of brain, breast, and
      prostate neoplasms, but are presently limited by lack of mature studies and
      reimbursement issues. Due to the high costs of radiotherapy technology
      acquisition and equipment maintenance, increasing staff salaries and tenuous
      reimbursement environment, care should be taken to avoid unnecessary duplication
      of services in the community.

PMID- 12806793
TI  - [Fecal incontinence--anatomy/pathophysiology].
AB  - The ano-rectal organ derives from two different structures, the proctodaeum and
      the hindgut. The uro-rectal septum splits off the hindgut from the anterior part
      of the cloaca. This means that the anorectum has the same origin of nerves and
      blood vessels as the anterior part of the cloaca, which derives from the uro
      genital sinus. In order to understand continence and defaecation, exact knowledge
      of the anatomy and physiology is compulsory. Studies in embryology are essential
      to the understanding of the anatomic and topographic structures.

PMID- 12806794
TI  - [Urinary incontinence in the woman--pathophysiology and diagnosis].
AB  - Since urinary incontinence is one of the most frequent female health problems and
      may severely affect a woman's life quality, knowledge about its pathophysiology,
      evaluation and therapy is very important. Even basic diagnostic tests can
      determine the type of incontinence (stress or urge urinary incontinence) thus
      permitting appropriate therapy to be initiated. The patients history, micturition
      diary, clinical evaluation, perineal ultrasound and urinalysis are important
      parts of these basic diagnostic tests. The positive stress cough test and the
      typical symptoms such as urine loss during physical activity point to the
      diagnosis of stress urinary incontinence. Frequency, nocturia and urgency with or
      without urine loss as well as more objective criteria such as micturition diaries
      and urinalysis indicate urge incontinence. Questions to help determine how
      quality of life is affected by the incontinence symptoms aid in deciding how
      urgent the treatment is. An urodynamic evaluation together with perineal
      ultrasound and cystoscopy is performed in patients with complex or recurrent
      urinary incontinence after surgery or with micturition disorders.

PMID- 12806795
TI  - [Urinary incontinence in the man--pathophysiology and diagnosis].
AB  - About 7-8% of men experience unvoluntary urinary leak. Incidence in patients
      older than 60 years is 2-3 fold increased. Urge incontinence is the mostly
      present, less frequent are overflow-incontinence/chronic retention and urinary
      stress incontinence. In men, prostate and bladder dysfunction as well as
      neurologic diseases are responsible for urinary incontinence. The baseline
      diagnostics include micturition protocols, the urologic clinical examination,
      residual urine determination and laboratory analyses of urine and blood. Extended
      diagnostics proceed to morphological and infectious etiologies and base on
      urodynamic evaluation.

PMID- 12806796
TI  - [Diagnosis and conservative therapy of anal fecal incontinence].
AB  - The main diagnostic tool for patients with anal incontinence is the anorectal
      physiology. The anorectal sphincter can be reliably tested. Due to the fact that
      an obstetric damage is the most common cause of anal incontinence, the transanal
      endosonography is the imaging method of choice for detecting a muscle defect.
      With high frequency ultrasound probes (preferable 10 Mhz) the pathomorphology of
      the sphincter can be studied in details. If conservative treatment is failing,
      the neurophysiology testing is helpful in deciding which surgical method
      (sphincter repair in case of an intact nervus pudendus, artificial sphincter or
      sacral stimulation in case of neuropathy). The conservative treatment includes
      increasing the internal sphincter muscle tonus by applying Phenylephrine locally
      or Loperamid per os. The biofeedback is basically a physical muscle training of
      the external sphincter with a visual or acoustic feedback of the muscle function
      to the patient. However, newer studies show that by this method the sensory
      function and the coordination of the anal sphincter are improving as well. With
      these conservative treatment options most of the patients suffering from anal
      incontinence can be treated satisfactorily.

PMID- 12806797
TI  - [Conservative therapy of urinary incontinence and bladder complaints in the
      woman].
AB  - Urinary incontinence and urogenital disorders are increasing. This is bothersome
      and impinges on the patient's quality of life. Early recognition, allowing early
      diagnosis, effective therapy as well as long-term prophylaxis are important. For
      diagnosis that quickly leads to a therapeutic decision, the anamnesis should
      specifically cover this area. Additionally, clinical examination, urinalysis
      including residual urine determination and cystoscopy for evaluating the bladder
      wall and a coughing test with a full bladder should be performed-all
      investigations easily done in the gynecologists's office. After diagnosis,
      treatment planning takes place. Urinary incontinence and urogenital complaints
      often have several pathologic causes. To improve success, various treatment
      possibilities should be optimally combined. Conservative therapy basics include:
      drinking and miction training, pelvic floor training including training aids and
      electrostimulation, pessaries, pharmaceutical therapies, estrogen as well as a
      through prophylaxis and treatment of infection. The primary treatment must be
      followed up with long-term prophylaxis. The most important requirements for a
      successful conservative therapy include knowing the various treatment basics,
      their uses, understanding and having the patience to follow through with an
      involved and time-intensive treatment plan. This work provides an overview of the
      various conservative treatments and their successful combinations.

PMID- 12806798
TI  - [Conservative and surgical therapy of urinary incontinence and bladder complaints
      in the man].
AB  - Treatment of incontinence and bladder complaints in the male should be directed
      to the cause whenever possible. Frequently, however, only symptomatic therapy is
      possible. Urge incontinence or overactive bladder due to obstruction should
      primarily be treated by eliminating the obstruction. Medical and surgical
      treatment methods are available for benign prostatic hyperplasia, bladder neck
      hypertrophy and prostatic cancer. In contrast, bladder neck sclerosis and
      uretheral strictures can only be treated surgically. Anticholinergics are
      primarily indicated if urge symptoms/incontinence persist after obstruction has
      been relieved or if urge incontinence occurs without obstruction. Seldom, in
      special cases injection of Botulinustoxin A or augmentation of the bladder may be
      indicated. Another possible cause of urge symptoms is urinary tract infection.
      This should be adequately treated according to resistance studies and the cause
      of the infection determined. In cases of overflow incontinence the infravesicle
      obstruction must be sought and treated. If limited detrusor contractability is
      the cause of overflow incontinence and the bladder cannot be emptied through
      pressmicturition, parasympathicometics may be of help. By insufficient effect,
      the procedure of intermittent self-catheterization must be taught. If this is not
      possible, the last resort is placement of a transuretheral or percutaneous
      catheter for continuous drainage. Stress incontinence is a rare complication in
      men, usually following prostatic surgery. It can be treated conservatively with
      pelvic floor training and alpha-adrenergic receptor agonists and if necessary
      surgically with submucosal collagen or silicon injections in the sphincter area
      or implantation of a sphincter prosthesis. Supravesicular urinary diversion is
      occasionally necessary after conservative and less invasive surgical measures
      have been exhausted and symptomatic suffering persists. Neurogenic disturbances
      in bladder capacity and/or emptying can be treated conservatively, medically,
      surgically or a combination of these depending upon the site of the lesion and
      the resulting urodynamic patterns.

PMID- 12806799
TI  - [Surgical therapy of female urinary incontinence].
AB  - Within the past years, surgical concepts for treating females with urinary
      incontinence have greatly changed. The spectrum of indications is becoming
      increasingly narrower. All possible conservative treatment modalities must first
      be attempted. Should the incontinence still continue to evoke social or hygienic
      problems, stress incontinence is usually treated with the minimally invasive TVT
      procedure (Tension-free Vaginal Tape), and in special cases, a modern
      modification of colposuspension is undertaken. Based on a success rate and
      specific complications, it is now known which slings and colposuspension
      techniques should no longer be used. Vaginal reconstructive surgery for pelvic
      organ prolapse, such as anterior and posterior repair and sacrospinous colpopexy
      are now obsolete for treating incontinence. Likewise discussed are operative
      procedures for rare forms of female incontinence and for urge incontinence,
      resistant to therapy.

PMID- 12806800
TI  - [Surgical therapy of fecal incontinence].
AB  - The algorithm of the treatment of the stool-incontinence starts with the
      differentiation between soiling and incontinence for flatus, liquid or formed
      faeces. In case of soiling, first all the causes that can be surgically solved
      should be treated. If this is not successful, the scheme of the incontinence
      treatment should be followed. The first step is a dietary consultation, which
      includes prescription of appropriate drugs against diarrhoea, constipation and
      proctitis. The anal-physiological examinations will inform about the elasticity
      of the ampulla recti, which can be reduced in inflammatory processes, it will as
      well inform about the innervations of the ano-rectum and allow an objective
      sphincter pressure. If dietary therapy and drugs intake fail, the anal sphincter
      should be more closely examined. An endosonography or a perineal sonography and
      in case of a rectocele with incontinence a defecography need to be performed. In
      case of intact or defective sphincter a biofeedback training is started. If this
      is not successful, a sphincter-repair is performed in case of defective
      sphincter. To maintain the result the biofeedback training is continued. In case
      of failure as well as in case of intact sphincter that cannot be treated with the
      help of the biofeedback training, sacral nerve stimulation is indicated. If this
      does not work, the next step will be a dynamic graciloplasty or an artificial
      bowel sphincter. Both these methods are also indicated when the sphincter is
      missing. If this fails an anus praeter would definitively improve the quality of
      life of the patients. With bedridden or heavy demented patients, the anus praeter
      is often the first choice of procedure. The costs of the expensive pacemaker of
      the sacral nerve stimulation or the dynamic graciloplasty as well as the
      artificial bowel sphincter scare the insurances. Talking about cost and benefit
      these appliances are interesting as already in two years the costs a permanent
      anus praeter is causing are higher than the price of these medical appliances. In
      this overview article, different surgical procedures are described considering
      their indications, results and operative principles. The step-by-step use of the
      proposed algorithm leads to an optimal treatment of the stool-incontinence.

PMID- 12806802
TI  - [The March 4, 2002 law: abandoned?].

PMID- 12806801
TI  - [Incontinence aids].
AB  - Incontinence aids are mechanical devices that help reduce, capture, absorb or
      channel urinary and stool loss. They can exert a significant positive impact on
      the quality of life and the social integration of those affected, as well as
      provide relief to their care-givers. Incontinence aids are used as a bridge until
      conservative and operative treatments bring continence, as a complement to other
      therapies or as a long-term course of treatment. The selection of appropriate
      incontinence aids, such as vaginal pessaries, penis clamps, and tampons, urinals,
      urine and faecal collectors, absorbing aids, urethral and suprapubic catheter
      channelling systems--requires a great deal of experience and an extensive
      assortment of various products in different sizes. In order to provide the
      patient with optimal treatment and advice where not only the products available
      are changing rapidly, but the conditions and environment as well (e.g., insurance
      reimbursement), close-knit teamwork is required among the physician, incontinence
      nurse, and the care-providers. Likewise to be considered is the fact that
      incontinence aids and care requirements vary significantly among the specialties
      of urogynaecology, urology, paraplegic centres, paediatrics and nursing homes;
      specific competence centres are therefore required for these areas.

PMID- 12806803
TI  - [Tribute to Stanislaw Tomkiewicz].

PMID- 12806804
TI  - [Tom].

PMID- 12806805
TI  - [The medical profile of children for whom a medico-social institution is
      recommended by the Departmental Commission of Special Education in Var].
AB  - Since September 1999, the Commission of Special Education (CDES) in the French
      department of Var implemented a computer system to electronically handle medical
      records and information in conformance with the circular of November 5, 1998. The
      study presented here is based upon the first 247 orientation requests entered in
      the academic year 1998-1999. Six groups of children were categorised according to
      the main diagnostic clusters: psychosis, non-psychotic personality disorders and
      behavioural disorders, mental deficiency and chromosomal anomalies, instrumental
      malfunctioning and learning problems, central neurological problems, and motor
      and sensory difficulties. This study describes the medical diseases and handicaps
      of children for whom a medico-social assistance has been requested for the first
      time at the CDES based upon the recommended orientations. The revision of
      database management system foreseen by the implementation of the OPALES programme
      (Guide to Management and Administration of local Special Education) will
      integrate the medical, social and administrative parameters, and it will allow
      for the provision of a more streamlined analysis of and response to the problems
      and issues of handicapped children which are addressed to the CDES. The system
      will constitute a sustainable database on the handicaps of the children
      throughout the entire department.

PMID- 12806807
TI  - [Effects of family or school disconnection on adolescents' health].
AB  - This article presents research on the health of adolescents who are in situations
      of either family or school detachment. Fourteen health indicators were used to
      investigate the physical, social and psychological well-being of adolescents. In
      addition, two separate scales were constructed to take into account family and
      school disengagement. As anticipated, the results prove that detachment from
      either family or school has a negative impact on health and this effect is
      amplified in cases of double detachment--both from family and school. The results
      also suggest an effect of contextual resilience since the school can play a
      protective role in for the health of adolescents who are in a situation of family
      disaffiliation. This research emphasises the need to analyse the risk and
      protective factors within a developmental and ecological theoretical framework to
      allow for the consideration of the dynamics involved between the different areas
      of life which are significant for an individual at a given moment in his
      development.

PMID- 12806808
TI  - [Medical characteristics of patients in long-term care facilities and predictions
      on the weight of their management].
AB  - The objective of this study was to highlight the heterogeneous nature of the
      medical profiles of patients living in long term care units (LCU) and to present
      the morbidity factors associated with-the weight and burden of ensuring long term
      medical care and treatment. Typology analysis, performed on a group of 600 LCU
      patients, highlights two types of patients: one who is characterised by having
      few or no serious diseases, and the other (representing nearly one-third of the
      sample population) corresponding to patients with serious poly-pathologies and
      requiring a high level of medical attention and nursing care. Factors associated
      with a higher level of care are diseases such as those related to cardiac or
      respiratory deficiencies. This predictive model for the burden of care could be
      used to measure the suitability between the state of the patients and the their
      optimum structures for care.

PMID- 12806806
TI  - [Life years lost and epidemiological transition in the Sfax region (Tunisia)].
AB  - OBJECTIVE: To assess the burden of disease in the Sfax region and identify the
      main diseases that are the cause of lost life years due to premature death.
      METHODOLOGY: The calculation of lost life years due to premature death was
      conducted using the demographic mortality data for the region obtained from the
      National Institute of Statistics combined with data on the classification of the
      causes of death collected through a survey on these causes conducted through a
      random sample taken from half of the deaths in the region. As described by Murray
      and Lopez, years of life lost as a result of premature death represent the
      difference between the age of death and an age corresponding to life expectancy
      falling between 65 and 85 years. RESULTS: Out of a total of 52,316 life years
      lost that were recorded 27,902 were in the male population and 24,414 in the
      female. The main diseases found in males which cause lost life years are
      accidents (24.9%), cardiovascular diseases (17.3%), communicable diseases (17%),
      respiratory diseases (10.8%), prenatal problems (59.5%), and cancer (7.5%). For
      women the main causes were cardiovascular diseases (26.5%), respiratory illness
      (15.5%), accidents (11.5%), communicable diseases (10.3%) and cancer (9.5%).
      RECOMMENDATIONS: These results marking the epidemiological transition in the
      region should serve to steer decision-makers to better rationalize and plan for
      health care costs and expenditure.

PMID- 12806809
TI  - [Economic contribution of gynecological and obstetrical ultrasound in an advanced
      strategy for the Zinguinchor region].
AB  - Aiming to strengthen the accessibility of ultrasound technology to rural
      populations, an advanced strategy ultrasound programme was implemented in the
      health districts of Sedhiou, Oussouye, Bignona and Ziguinchor all located within
      Casamance in Senegal. Within the first year of activity (January 1, 2001-December
      31, 2001), the team from the regional health centre (RHC) was dispatched 56
      times. Ultrasound scans were performed in the homes of 1,273 patients among which
      192 were referred to the RHC for specialised follow-up and treatment. The
      financial benefit for the RHC totaled 3,120,000 francs; 2,612,500 francs for the
      district hospital; and 3,561,300 francs for the population at large. The advanced
      strategy for performing ultrasound scans has therefore been economically
      profitable at the community level as much as at the level of health structures.
      Through supporting the activities of the district hospitals, the RHC contributed
      technical support and increased the potential, not solely for the treatment of
      disease but for the health services overall. The revenue generated has given
      managers a greater possibility to improve health care and services. The
      decentralisation programme and reduction in the cost have decreased the
      unsatisfied needs in ultrasound services by making the technology more
      financially and geographically accessible. Thus, by saving input costs in terms
      of time, transportation and capital, the practice of ultrasound scans in district
      hospitals has been strengthened and has improved the capacity to provide care and
      treat the population's health problems. The continuation of this programme is
      advantageous, but necessitates two complementary actions: enhancing of the
      technical level and capacity of the district hospitals with the installation of
      ultrasound technology and equipment, and raising the level of knowledge by
      training staff in administering ultrasound scans.

PMID- 12806810
TI  - [Tobacco: knowledge, reasoning and opinion of high school students in Doubs.
      Reflections on prevention].
AB  - The prevalence of smoking has increased among young people aged 14 to 18 between
      1993 and 1999, and most notably among girls within the same period. These
      observations illustrate the necessity for significant changes in mass media
      campaigns and education programmes related to the prevention of smoking among
      youth. The objective of this survey, initiated by the city of Besancon and the
      French National Mutual Insurance of Doubs, was to describe and analyse the
      knowledge and rationale of high school students on tobacco and their opinions in
      terms of prevention. Twelve public and private high schools in Besancon and
      Morteau (Doubs-France) participated in the survey; the group also represented a
      mix of general and professional schools. The questionnaire was filled out by 970
      students selected at random. 96% of the students indicated cancer as being the
      main illness linked to tobacco and 94% stated that second-hand smoke constitutes
      a health risk. 61% admitted to seeking out the psychoactive effects of smoking.
      The students responses confirm that the types of messages relayed in a smoking
      prevention campaign which have an impact on them are: evoking fear of death (74%)
      and the use of humor (16%). One-third of high school students find that it is
      unacceptable to forbid smoking on school premises. The knowledge of the dangers
      related to smoking is not sufficient to keep young people from smoking and
      confirms that an educational approach based solely on knowledge and facts will
      not be sufficient to decrease their tobacco consumption. It is important to take
      into account the image that young people have of tobacco as a means to combat
      stress in future prevention strategies and campaigns.

PMID- 12806811
TI  - [Why a graduate diploma specializing in the management of health projects in Cote
      d'Ivoire?].
AB  - The achievement of the "health for all" objectives represents a particular
      challenge for developing countries where the morbidity rates and the number of
      deaths are increasing on an annual basis. In order the face this situation in
      Cote d'Ivoire, health action programmes were initiated on the one hand, and on
      the other, a type of decentralised responsibility was established for the
      coverage of the population's health at the health district level where these
      programmes are administered. However, serious insufficiencies were noted in the
      management of health projects as well as a lack of follow-up and evaluation by
      trained staff. Furthermore, it is imperative to have personnel qualified in
      managing health projects. In fact, this specialised training will allow for the
      attainment of knowledge and competencies necessary for the effective conception,
      development, planning, implementation and management of health action programmes
      at the national level as much as the district level. In addition, these health
      project specialists will be able to get involved at several levels in positions
      such as managers of national projects, technical advisors for national health
      directives, district managers, etc. Such training would contribute to the
      improvement of the population's health status and thus address the challenge of
      health for all.

PMID- 12806812
TI  - [Managing the air pollution in Paris resulting from diesel trains: inquiry or
      action].

PMID- 12806813
TI  - [The development of a core set of quality of care indicators in a psychiatric
      hospital].
AB  - The Camille Claudel psychiatric hospital developed a table of a core set of
      quality indicators based upon a standarized description form and a critical
      appraisal grid that were recently released. The authors' aims were to study the
      validity of these tools and the main methodological difficulties faced
      professionals in the field in the process of developing their indicators. A multi
      disciplinary working group from this hospital developed 43 indicators which were
      subsequently analysed by methodologists. Out of the 43 indicators, variables
      needed to calculate the indicators were incomplete for 30, the sampling method
      inappropriate in five, the means of data quality control not defined in 18, and
      the stratification and adjustment concepts mixed up in 6. Moreover, 14 indicators
      were excluded due to their lack of relevance or feasibility. The experience
      demonstrates the capacity of a hospital, without internal epidemiological or
      methodological competence, to develop its own set of quality indicators. The
      provision of methodological assistance and supervision, based upon tools proven
      to be relevant and effective, seems to be crucial in training professionals and
      helping them to select and improve their indicators.

PMID- 12806814
TI  - [Management of heart failure: ambition and reality in the early 21st Century].
AB  - At the beginning of the 21st century, we are faced with a discrepancy between the
      favourable results produced by a series of large randomised controlled trials on
      heart failure and their poor implementation into clinical practice. (ACE
      inhibition, beta-blockade, aldosterone antagonism). The organisation of care for
      patients with heart failure needs improvement. This is why the first large
      international survey was initiated to evaluate perception and practice of primary
      care physicians (PCPs) in the management of heart failure. In general, PCPs
      appeared well-informed about diagnostic steps and therapeutic interventions. In
      practice, most patients received appropriate diagnostic tests. The uptake of ACE
      inhibitors was high, but few patients were receiving recommended doses. Beta
      blockers are currently underused but this situation may be changing rapidly.
      Though "IMPROVEMENT" might suggest we get it right fairly often, it does also
      indicate that the process is haphazard and that we could be much more efficient.

PMID- 12806815
TI  - [Rational diagnosis of chronic heart failure].
AB  - Congestive heart failure is associated with a high mortality and morbidity. The
      aetiology of heart failure and the presence of exacerbating factors should be
      carefully assessed in all cases. The extent to which the cause of heart failure
      should be pursued by further investigations will depend on the resources
      available and the likelihood that a precise diagnosis will influence treatment.
      The clinical suspicion of heart failure should be confirmed by more objective
      tests, particularly aimed at assessing cardiac function. To achieve this goal a
      variety of non-invasive and invasive tests are available. For follow-up studies
      echocardiography and to a lesser extent chest x-ray may be helpful. It is
      expected that measurement of plasma concentration of natriuretic peptides may add
      important information to the diagnostic process of heart failure and will
      identify those patients at greatest risk for serious cardiovascular events. In
      the future, the development of new techniques in non-invasive diagnostic tests
      such as contrast echocardiography, computer tomography and cardiac magnetic
      resonance imaging will extend the diagnostic spectrum of heart failure.

PMID- 12806816
TI  - [Pharmacotherapy of chronic heart failure].
AB  - In recent years improvement of pharmacotherapy has led to a reduction of
      morbidity and mortality of heart failure patients. According to current evidence
      therapy of chronic heart failure should include ACE inhibitors and beta-Blockers
      to relieve symptoms and improve prognosis. In patients with fluid overload
      diuretics should be added. If symptoms persist or in patients with atrial
      fibrillation cardiac glycosides are indicated. Additional spironolactone can
      reduce mortality in patients with NYHA class III-IV. If ACE inhibitors are not
      tolerated or contraindicated AT1 receptor blockers should be considered as second
      line drugs. Evidence-based management strategies can improve prognosis in heart
      failure but medication has to be individualized for every patient depending on
      the presence of comorbid conditions.

PMID- 12806817
TI  - [Surgical strategies for the treatment of heart failure].
AB  - Currently, heart transplantation is the gold standard of treatment for patients
      with end-stage heart failure. With the number of donor organs steadily
      decreasing, new surgical strategies have evolved. Selected patients with
      ischaemic cardiomyopathy or mitral valve insufficiency may be suitable candidates
      for conventional surgical procedures. New developments regarding assist devices
      such as LVAD and TAH increase our chances of employing these systems as a
      definite treatment option (destination therapy). New innovative concepts like
      external ventricular reshaping (Myosplints, CorCap) or left ventricular
      reconstruction are currently undergoing clinical evaluation. The clinical results
      of cardiac resynchronisation therapy offer a new treatment option for patients
      with LBB. The value of different treatment options and their role in modern
      surgical heart failure management is discussed.

PMID- 12806818
TI  - [Therapeutic perspectives in heart failure]].
AB  - Many different diseases may lead to heart failure. Nevertheless, the symptoms and
      pathophysiological changes in heart failure are uniform as are the basic
      principles of treatment. Although significant progress has been achieved in
      understanding the biology of heart failure and the therapeutic options, the
      quality of life of heart failure patients and their survival are often poor.
      Since cardiac transplantation as a final therapeutic option is limited by the
      availability of donor organs, new strategies and technologies need to be explored
      to treat the failing heart effectively. Approaches to improve the medical therapy
      of heart failure mainly focus on strategies to escape the vicious circle of
      decreased contractility and neurohumoral activation. Substances with promising
      experimental and clinical results include neutral endopeptidase inhibitors,
      endothelin antagonists or cytokine inhibitors, e.g. TNF antagonists. Mechanical
      and electrical devices are under development such as left ventricular assist
      devices (LVADs), biventricular pacemakers and artificial hearts, which may become
      valuable alternative therapies. Gene therapy approaches aim to improve the
      vascularization of the heart, the Ca-homeostasis of the myocytes or the survival
      of cardiac cells in disease. Finally, cellular cardiomyoplasty is a relatively
      novel approach to replace or support the cardiomyocytes of the diseased heart by
      implanting new ones. Which cell type under which conditions will turn out to be
      the most suitable is still unknown and subject to debate. Ongoing clinical
      studies will only help to demonstrate the safety and feasibility of this
      technique but not determine its long-term efficacy. It is highly desirable that
      one of these new therapeutic strategies or a combination of them will have a
      significant impact on the future management of heart failure. Currently, our main
      clinical focus must be to treat as many patients as possible with drugs that are
      known to improve symptoms and survival, like ACE inhibitors, beta-blockers,
      cardiac glycosides, diuretics and spironolactone.

PMID- 12806819
TI  - [Implementation of psychosocial care in pediatric cardiology. Results of a
      national survey].
AB  - In the German health care system patient self-help groups assume growing
      importance. The aim of the umbrella organisation for self help groups in
      paediatric cardiology (Bundesverband Herzkranker Kinder e.V., BVHK) is to
      continuously improve comprehensive health care to children with heart diseases
      and their parents. One of the most important aims of the BVHK is to implement
      psychosocial services for inpatients. In some recent projects the BVHK has
      analysed the current structures of psychosocial care in German departments of
      paediatric cardiology. Existing structures are compared with the optimal
      standards of psychosocial care. Selected results of these projects are described
      in this article.

PMID- 12806820
TI  - [Certification and quality management of a complex university cardiac center
      according to law EN ISO 9001: 2000].
AB  - Quality management systems can improve quality in health care units. The
      introduction of a quality management system according to ISO 9001: 2000 in a
      university department of cardiovascular surgery is described. First a thorough
      analysis of all processes of patient treatment and clinical research was
      obtained. Multiple interfaces had to be defined to different departments as well
      as to administration units. All necessary resources were evaluated and optimised.
      Customer satisfaction was evaluated by surveys of patients and collaborating
      physicians. Quality rounds including physicians, nurses and technicians were
      instituted. Based on these preparatory works all processes including their
      responsibilities and necessary resources were redefined and described in the
      quality manual. After 18 months' of certification of our quality management
      system according to ISO 9001: 2000 was recommended by an independent, accredited
      organisation. In summary, certification of a university department of
      cardiovascular surgery according to ISO 9001: 2000 is possible and may represent
      the first step towards total quality management. In complex health care units the
      certification of individual departments may help to generate a consciousness for
      quality on the road to total quality management.

PMID- 12806821
TI  - [Guideline report of the Guideline Group of Hessen--general practice therapy
      circle: management of chronic heart failure].
AB  - In this report, the Guideline Group of General Practitioners (GPs) in Hessen
      (Leitliniengruppe Hessen--Hausarztliche Pharmakotherapiezirkel) describes the
      motivation and working procedure for developing an evidence-based GPs' guideline
      for the management of chronic heart failure. Insufficient use of recommended drug
      therapy and the frequency of probably avoidable hospitalisation are regarded as
      important deficiencies in the medical care of patients with chronic heart
      failure. In this report the guideline group demonstrates the identification and
      interpretation of evidence for their recommendations and suggests indicators for
      monitoring adherence to the guideline using prescription data. The topics raised
      in this report follow the checklist of the German Manual for Clinical Practice
      Guidelines (Germ-CPG) published by the German Association of the Scientific
      Medical Societies (AWMF) and the German Guideline Clearinghouse. The guidelines
      have been developed in the context of the pharmacotherapeutic quality assurance
      program of the Association of Health Insurance Physicians of Hesse (KV Hessen)--a
      well established program of the KV Hessen and the sickness funds (VdAK/AEV.) The
      members of the guideline group have been engaged as moderators of quality circles
      for about 12 years.

PMID- 12806822
TI  - [Positron emission tomography--a technique for the routine practice of ambulatory
      care?].
AB  - Positron Emission Tomography (PET) has been regarded as a breakthrough technology
      that helps diagnoses various conditions. PET was developed in the United States
      during the 1960s, and has since diffused rather slowly into most modern health
      care systems. Germany is an exception, as here the diffusion of PET has been
      rapid, and more than 70 PET scanners have been installed. At present, PET scans
      are not included in the health care basket though they are often used and members
      of the statutory sickness fund frequently seek reimbursement for this technology.
      The Standing Committee therefore conducted a formal inquiry into the value of PET
      scanning in publicly funded (statutory) ambulatory health care. The Committee's
      decisions were based on a technology assessment of PET. This report found that
      PET has been approved by the German Federal Institute for Drugs and Medical
      Devices (BfArM) for five indications. The evidence for these five indications was
      compared to that for other diagnostic methods such as magnetic resonance imaging.
      The assessment found no convincing evidence to support the introduction of PET
      into statutory ambulatory health care in Germany. In April 2002 the Standing
      Committee consequently denied approval for the reimbursement of PET as a publicly
      funded diagnostic procedure.

PMID- 12806823
TI  - [Between habilitation and junior professorship: alternatives to general practice
      and clinical medicine].
AB  - The junior professorship is a new model in Germany to overcome problems of the so
      called "habilitation", which has up to the present been the typical career path
      for future scientists. The junior professor career promotes own research but
      hampers young scientists in their clinical activity and education. Here, we plead
      for a research doctorate in clinical medicine and general practice finally
      leading to a PhD degree for the following four reasons: (1) Having lower
      thresholds and increasing the motivation for applicants, the entry into a PhD
      model is less formalised than for a habilitation procedure. (2) Compared to the
      junior professorship, it allows for a combination of, and exchange between,
      clinical and scientific requirements more easily. (3) The applicants' scientific
      creativity and research can be reliably assessed. (4) It protects applicants from
      a strong personal dependence on the head of department without neglecting the
      development of significant clinical excellence.

PMID- 12806824
TI  - Nanotechnologies and health.

PMID- 12806825
TI  - [Commentary about the 16th National Symposium of Medicinal Chemistry Italian
      Chemical Society--Sorrento, September 18-22, 2002].
AB  - The Congress was been structured on four main sections: 1) receptors chemistry;
      2) developments in pharmaceutical analysis; 3) computational molecular design; 4)
      antineoplastic, antiviral, antibacteric and cytostatic agents. In the present
      review we summarize the more important communications, and we emphasize that all
      the communications were of a high standard.

PMID- 12806826
TI  - Release from transdermal delivery systems. Application of a new non isothermic
      method to Trans-Ver-Sal patches.
AB  - In this paper a new non isothermic method for the determination of the release
      drug rate constant (k) from a transdermal delivery system is proposed. The new
      method was applied to transdermal patches Trans-Ver-Sal. The results obtained
      prove to be able to release salicylic acid of transdermal system and the
      effectiveness of the new method propose.

PMID- 12806827
TI  - Hydrolytic properties of per (3,6-anhydro, 2-O-carboxymethyl) alpha cyclodextrin
      complexes of Ce (III) and Eu (III): application to soman (GD) degradation.
AB  - Per (3,6-anhydro-2-O-carboxymethyle) alpha-cyclodextrin ([ACX]) is a polydentate
      analog of EDTA, a well-known cation chelating reagent. ACX exhibits strong
      affinities in vitro for uranyl, cobalt and also for lanthanids such as Europium
      and Cerium. The hydrolytic activities of ACX-Eu and ACX-Ce complex were directly
      tested on an organophosphorous compound: the neurotoxic Soman (GD), an inhibitor
      of acetylcholinesterase (ACHE from rat brain). It was found a three fold
      reduction of soman activity when measured in the presence of Ce-ACX complex.
      Conversely, Eu-ACX effect did not result in soman inhibition variation under
      physiological conditions. It is suggested that, considering usual organometallic
      complex of cyclodextrin, such direct complexes would be of interest in the design
      of pseudo-enzyme systems for phosphoester hydrolysis.

PMID- 12806829
TI  - Analysis of the expenses for drugs in the stationary departments of the united
      regional hospitals.
AB  - The rate of the health expenses is an important factor for the fulfillment of the
      actions in the field of the healthcare. The means, collected from different
      financial sources/the National budget-98% from the necessary means, receipts out
      of the budget-1.5%, collected means from the population-0.5%/are spent as it
      follows: for the National health institutions of the municipalities-65%; for the
      health institutions of national level and for the central supply with some kind
      of drugs, serums and vaccines-17%; for the health institutions, financed directly
      from the International Fond-18% from the means. The main part from the means are
      spent for salaries and for the social security of the staff.

PMID- 12806828
TI  - Comparison of intestinal absorption of selected calcium organic salts through the
      rat jejunum in vitro.
AB  - The calcium penetration rates through the rat's ileum were determined for calcium
      fumarate, calcium gluconate and calcium chloride in solution by means of a set
      for determination of drug penetration through membranes. The highest penetration
      rate of calcium was observed for the calcium fumarate solutions, a lower one for
      calcium gluconate solutions and the lowest--for calcium chloride solutions. The
      calcium penetration rate was independent from the calcium doses in the studied
      concentration range. The obtained results suggest that calcium fumarate, till now
      not used in therapy might find an application in the corrective therapy of
      calcium deficiency.

PMID- 12806830
TI  - Synthesis of some new pyrimidine and fused pyrimidine derivatives (Part 2).
AB  - 6-Oxo-4(2-thienyl)-2-thioxo-1,3-dihydropyrimidine-5-carbonitrile (1) was
      synthesized and reacted with alkyl halides to give the S-alkyl compounds (2a,b),
      which reacted with phosphorous oxychloride to yield (3a,b). Reaction of 3a,b with
      phenyl-hydrazine, hydrazine hydrate, ammonia, acid hydrazides and thiourea leads
      to formation of the compounds (4a,b), the dihydrazino compound derivative (5),
      the amino compounds (7a,b), triazolopyrimidine derivatives (9a-d), and the
      mercapto compounds (10a,b), respectively. Treatment of (10a) with chloroacetone
      gave (11a), which condensed with benzaldehyde giving the tricyclic compound (12).
      Also (10b) reacted with ethyl chloroacetate followed by hydrolysis and
      cyclization yielded (14). Heating of (5) gave (6), which reacted with sodium
      nitrite and/or carbondisulphide and give (15) and (16), respectively.

PMID- 12806832
TI  - Release and skin permeation studies of Naproxen from hydrophillic gels and effect
      of terpenes as enhancers on its skin permeation.
AB  - The skin permeation parameters of Naproxen through albino mouse abdominal skin
      was investigated. Out of 5 formulations those prepared from carbomer gels showed
      promising results and were chosen for investigating enhancing effect of various
      terpene alcohol viz. Geraniol and Nerolidol and cyclic terpenes viz menthol and
      thymol on skin permeation of Naproxen. Out of the four terpenes studied Geraniol
      exhibited the highest enhancing effect with enhancement ratio 4.6, while
      Nerolidol had an enhancement ratio 4.2. The cyclic terpenes had less prompt
      enhancing effect compared to the alcohol terpenes, out of the two, methol showed
      the largest effect with an enhancement ratio of about 3.7 and thymol had an
      enhancement ratio of 3.5.

PMID- 12806831
TI  - Dissolution, bioavailability and ulcerogenic studies on piroxicam-nicotinamide
      solid dispersion formulations.
AB  - Solid dispersions with different ratios of Piroxicam and Nicotinamide (as a
      carrier) were prepared by fusion method. Drug-carrier interactions in the solid
      state were ascertained using phase-diagram, X-ray diffraction (XRD) and
      Differential scanning colorimetry (DSC). Select ratios of the formed piroxicam
      nicotinamide solid dispersions and their corresponding physical mixtures were
      formulated into tablets and capsules. The dissolution characteristics of the
      formed solid dispersions, physical mixtures and their formulations were compared
      with pure piroxicam in 900 ml of 0.1 N HCl (pH 1.2) at 37 +/- 0.5 degrees C, 50
      rpm using USP XXI paddle apparatus. Solid dispersion capsule PNC1 (containing 1:5
      -drug-carrier ratio solid dispersion) and the corresponding physical mixture
      capsule PNC1A were used for bioavailability studies in healthy human volunteers.
      Further, ulcer indices of the prepared solid dispersion and their corresponding
      physical mixture were compared with pure piroxicam in rats. The DSC, XRD and
      phase diagram indicated the formation of solid dispersed system. The prepared
      dispersion showed better dissolution than the corresponding physical mixture and
      pure drug. The fabricated formulation complied with the pharmacopoeial limits for
      physico-chemical properties and the solid dispersion capsules PNC1 and PNC2
      (containing 1:9 ratio of drug to carrier solid dispersion) showed 3 and 6.6 fold
      increase and 3.2 and 8 fold increases in dissolution rate compared to the
      corresponding physical mixture capsules (PNC1A and PNC2A), respectively. The
      solid dispersion capsule PNC1 showed significantly higher absorption and
      dissolution and consequently better bioavailability than the corresponding
      physical mixture capsule (PNC1A) in healthy human volunteers. The ulcer indices
      of the prepared dispersions were significantly lower than the corresponding
      physical mixture and pure drug.

PMID- 12806833
TI  - Antituberculosis agents. VII. Synthesis and in vitro evaluation of
      antimycobacterial activity and cytotoxicity of some N-piperazinyl quinolone
      derivatives.
AB  - A series of N-[2-(2,4-dichlorophenyl)-2-oxoethyl] and N-[2-aryl-2-benzyloxyimino
      ethyl]piperazinyl quinolones (5-13) have been prepared as part of a study to
      examine the relationship between structural modification at 7-position and
      activity against Mycobacterium tuberculosis. Primary screening was conducted at
      concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv using BACTEC
      460 radiometric system and BACTEC 12B medium. The actual minimum inhibitory
      concentrations (MIC) were determined for compounds demonstrating at least 90%
      inhibition in the primary screening. The results demonstrate that substitution of
      phenyl ring with 4- fluoro, 2, 4-difluoro and 2,4-dichloro groups resulted in
      variable inhibition percentage (Inh% = 7-101). Despite the significant
      antituberculosis activity of ciprofloxacin and norfloxacin derivatives containing
      2-(2,4-dichlorophenyl)-2-oxoethyl moiety (MIC = 0.39 & 6.25 micrograms/ml),
      compounds with 2-aryl-2-(hydroxyimino)ethyl, 2-aryl-2-(benzyloxyimino)ethyl and 2
      aryl-2-(4-chlorobenzyloxyimino)ethyl did not show any activity (MIC > 6.25
      micrograms/ml, Inh% = -7 to 75). Active compounds were also screened by serial
      dilution to assess toxicity to a VERO cell line. While the most active compound
      5a was not soluble in tissue culture media, compound 5b showed IC50 = 5.3
      micrograms/ml.

PMID- 12806835
TI  - Extrabuccal infralabial secretion outlets in Dromophis, Mimophis and Psammophis
      species (Serpentes, Colubridae, Psammophiini). A probable substitute for 'self
      rubbing' and cloacal scent gland functions, and a cue for a taxonomic account.
AB  - Extrabuccal infralabial secretion outlets (ILOs), periodically absent and
      heretofore non-described, have been found in nineteen species representing three
      of the eight psammophine snake genera. These infralabial outlets are thought to
      be non-existent in the other five genera. A few psammophines representing four
      genera, among which three of the five without ILOs, are characterised by their
      'self-rubbing' behaviour, for which they employ an external narial valve bearing
      a secretion outlet of a special nasal gland. Such a valve is here reported for
      representatives of all eight genera. It is proposed that all psammophines perform
      self-rubbing to enable subsequent chemical marking of substrate and conspecific
      individuals. The newly found infralabial outlets, however, serve for direct
      chemical marking of conspecifics. This direct marking seems to substitute for a
      function of both the special nasal gland and the cloacal scent glands during
      social activity of the snakes in trees or shrubs. This hypothesis and the
      relationship of the observed traits with the presumed advantages of a thin and
      short hemipenis are discussed. A taxonomic implication is suggested.

PMID- 12806836
TI  - Sense-organ-like parietal pits found in Psammophiini (Serpentes, Colubridae).
AB  - In several psammophine snake species, small sense-organ-like pits have been
      discovered occurring on the top of the head. These pits show a heretofore non
      described structure. In numbers of one to four per head, they are present in
      Dromophis lineatus, Malpolon monspessulanus, several Psammophis species and
      Rhamphiophis rubropunctatus, but not in all individuals which is unrelated to
      sex. The reason for their sporadic occurrence remains obscure. Their equally
      obscure function is discussed in relation to the presumed functions of already
      known upper-head 'pits' in snakes. A histological study is in preparation.

PMID- 12806834
TI  - Cerebral metabolism and consciousness.
AB  - In vivo 13C magnetic resonance spectroscopy studies of the brain have measured
      rates of glutamate-glutamine cycle (Vcyc) and glucose oxidation (CMRglc(ox)) by
      detecting 13C label turnover from glucose to glutamate and glutamine. In both the
      awake human and in the anesthetized rat brains Vcyc and CMRglc(ox) are
      stoichiometrically related, and form a major pathway in which approximately 80%
      of the energy from glucose oxidation supports events associated with glutamate
      neurotransmission. The high energy consumption of the brain at rest and its
      quantitative usage for neurotransmission reflect a high level of neuronal
      activity for the non-stimulated brain. This high activity supports a
      reinterpretation of functional imaging data, e.g., where the large baseline
      signal has commonly been discarded. Independent measurements of energy
      consumption (delta CMRO2%) obtained from calibrated fMRI equaled percentage
      changes in neuronal spiking rate (delta nu %) measured by electrodes during
      sensory stimulation at two depths of anesthesia. These quantitative biophysical
      relationships between energy consumption and neuronal activity provide novel
      insights into the nature of brain function. The high resting brain activity is
      proposed to include the global interactions constituting the subjective aspects
      of consciousness. Anesthesia by lowering the total firing rates correlates with
      the loss of consciousness. These results, which measure the localized neuronal
      response and distinguish inputs of peripheral neurons from inputs of neurons from
      other brain regions, fit comfortably into the neuronal scheme of a global
      workspace proposed by Dehaene and Changeux.

PMID- 12806837
TI  - Soil macroinvertebrates as indicators of pollution by heavy metals.
AB  - A broad range of soil pollutants were found to decrease with distance from a zinc
      smelter from 35,000 to 77, 8270 to 40 and from 190 to less than 1 ppm for zinc,
      lead and cadmium, respectively. Along this gradient, observed species richness of
      soil macro-organisms seemed to be more affected by the land-use type than by soil
      pollution--minimum in crops (21), maximum in woody sites (126). IndVal index
      allowed isolation of 21 indicator species from the 339 morphospecies identified.
      Most of these indicator species were characteristic of the unpolluted sites: only
      two diplopods and one gastropod from polluted poplar plantations, and none from
      the most polluted site. Since soil invertebrates respond to different
      environmental factors, including direct effect of heavy metals, we suggest there
      may be some confounding factors generating spurious relationships between the
      values of species as bioindicators and the pollution status they are supposed to
      indicate.

PMID- 12806838
TI  - Spatio-temporal growth dynamics of a subAlpine Pinus uncinata stand in the French
      Alps.
AB  - Natural forests are characterised by a high level of both spatial and temporal
      heterogeneity. The major processes involved in the creation and maintenance of
      forest heterogeneity in temperate climates are small-sized canopy disturbances.
      The resulting openings also modify the growth conditions for the remaining trees.
      The analysis of tree growth responses using dendrochronological techniques allows
      the reconstruction of the time sequence of the disturbances. The radial growth
      analysis is coupled here with both a spatial analysis and a demographic analysis
      of the forest structure. The age classes are temporally organised in cohorts and
      spatially distributed in spatial aggregates. The analysis of the most documented
      disturbance event allowed us to determine the size of the disturbance response
      patch (between 0.036 and 0.073 ha) and the duration of the disturbance (six
      years). We considered that this small-scale disturbance event may have been
      caused by the fall of a single tree and has freed the surrounding trees of its
      competition.

PMID- 12806839
TI  - Factors influencing the toxicity of xenobiotics against larval mosquitoes.
AB  - In order to examine the factors influencing xenobiotic toxicity against larval
      mosquitoes, the larvicidal performances of two conventional insecticides
      (temephos and Bacillus thuringiensis var. israelensis: Bti) and a new potential
      phyto-insecticide (decomposed leaf litter) were compared under different
      conditions against three detritivorous larval mosquito types. Bioassays performed
      under standard conditions indicated differential tolerance levels according to
      the xenobiotic and the larval type. Bioassays performed under different
      conditions of xenobiotic dose and geometry of the water column indicated
      differential effects of those parameters on mortality rates. This allowed us to
      distinguish the performances of temephos versus those of Bti and leaf litter.
      These toxicological performances were examined as indicators for analysis of
      xenobiotic bioavailability for mosquito larvae in environmental water, and also
      for their comparative interest in field mosquito control.

PMID- 12806840
TI  - Potential for individual recognition in acoustic signals: a comparative study of
      two gulls with different nesting patterns.
AB  - We test relationships between structure of acoustic signal used for individual
      recognition and nesting ecology among two gulls: the black-headed gull (Larus
      ridibundus), in which chicks remain in the nest, and the slender-billed gull (L.
      genei), in which chicks leave the nest after hatching to form creches. A striking
      difference between both species is the presence of two fundamental frequencies in
      the slender-billed gull's call and only one in the black-headed gull's call. Our
      study shows that the potential for individuality coding is more important in the
      species where the offspring experiment the greatest constraints--due to their
      nesting pattern--to identify their parents.

PMID- 12806841
TI  - Short inverse complementary amino acid sequences generate protein complexity.
AB  - Inversions of short genomic sequences play a central role in the generation of
      protein complexity. More than half of the 1300 motifs registered in ProSite have
      protein inverse complementary sequences (princoms) among proteins registered in
      SwissProt. The observed number of princoms occurrences exceeds by far the
      expected number (p < 10(-10)). Princoms often endow their host proteins with a
      whole new range of biochemical and physiological capabilities, including the
      possibility of intramolecular and intermolecular disulfide bond formation. These
      results support the idea that, like the duplications, the inversions of small
      genomic fragments have been a fundamental mechanism for shaping genomes.

PMID- 12806842
TI  - [Hope instead of anxiety and anger].

PMID- 12806843
TI  - [Job satisfaction and treatment outcomes. Support is vital for nursing quality].

PMID- 12806844
TI  - [Work satisfaction in the acute hospital].

PMID- 12806845
TI  - [Spitex. Good working climate promotes satisfaction].

PMID- 12806846
TI  - [Ambulatory psychiatric care. Hidden suffering at home].

PMID- 12806847
TI  - [Job experience and competence. Value and power in nursing].

PMID- 12806848
TI  - ["Eating" in nursing care of demented patients. Nutrition as a part of
      "psychological nursing"].

PMID- 12806849
TI  - [On solid foot].

PMID- 12806850
TI  - [Evaluation of nursing education].

PMID- 12806851
TI  - [The zest of little trifles].

PMID- 12806852
TI  - [Work satisfaction in EMS. A site where one can fully realize oneself].

PMID- 12806853
TI  - [Work satisfaction and awareness of the profession. Who is really interested in
      the proper role of the nurse?].

PMID- 12806854
TI  - [Outside views on the nursing universe. Through the garret window of the
      ethnologist].

PMID- 12806855
TI  - [Development of palliative care in the Vaud canton. 3 mobile teams are in place].

PMID- 12806856
TI  - ["In psychiatry, one takes time to enter into a relationship" (interview by
      Brigitte Longerich)].

PMID- 12806858
TI  - [Are hormone substitution and vitamins dangerous for elderly women with heart
      diseases?].

PMID- 12806859
TI  - [After the early termination of the Women's Health Initiative study. New American
      recommendations for postmenopausal hormone therapy].
AB  - One treatment-arm of the Women's Health Initiative (WHI) study was recently
      terminated because the overall risks of hormone treatment were considered to
      outweigh the benefits. The main findings were an increased risk of venous
      thromboembolism and a decreased risk of osteoporotic fractures with treatment. No
      beneficial effects on cardiovascular disease could be detected. The North
      American Menopause Society (NAMS) Advisory Panel has given the following
      recommendations concerning hormone therapy: The primary indications are vasomotor
      and urogenital symptoms. The only indication for progesterone treatment is for
      endometrial protection. Hormones should not be prescribed for primary or
      secondary prevention of coronary heart disease. Alternative therapies should also
      be considered for the prevention of osteoporosis. A short duration of therapy and
      lower-than-standard doses are preferable. Establishing an individual risk profile
      is essential. The author of this article also emphasizes a restrictive attitude
      for patients with increased risk of thromboembolic disease.

PMID- 12806860
TI  - [Ultrasound fetal nuchal translucency screening at 12-13 weeks of gestation. More
      effective method of selection for amniocentesis than the maternal age].

PMID- 12806862
TI  - [Different principles for EBM and evidence-based education].

PMID- 12806861
TI  - [Increased mortality and morbidity among children to single parents].

PMID- 12806863
TI  - [Available knowledge. Handheld computers in the clinical everyday].

PMID- 12806864
TI  - [Crisis of the clinical research. Re-establish professors at the university
      hospitals!].

PMID- 12806866
TI  - [Medical development is costly--the share of health care in the GNP must be
      increased].

PMID- 12806865
TI  - [More difficult recruitment of physicians to geriatric care because of a proposal
      from the National Board of Health and Welfare].

PMID- 12806867
TI  - [Thoughts about stress and obesity].

PMID- 12806868
TI  - [Why to be a member of the Swedish Medical Society?].

PMID- 12806869
TI  - [About sick leave].

PMID- 12806870
TI  - [Proton pump inhibitors and chronic requirement].

PMID- 12806871
TI  - [Adolescent and family crisis].

PMID- 12806873
TI  - [Sources of errors in blood glucose self-monitoring in 100 young diabetics].
AB  - Self-monitoring of blood glucose (SMBG) has become increasingly important in the
      treatment plan of people with diabetes. Identifying sources of error in SMBG can
      have a significant clinical impact. The objective of the present study was to
      evaluate the testing skills in diabetic children and adolescents. The study
      included 100 patients (46 females and 54 males) with an age of 8-18 years and a
      mean duration of diabetes of 4.5 years. They were autonomous for SMBG: an
      experienced diabetes nurse had taught earlier how to proceed. The daily frequency
      of SMBG was 4 in 79 patients, 3 in 11, and 2 in 10. The observations of their
      performance of blood glucose monitoring skills were done twice, during 2
      consecutive visits at the diabetes clinic at a mean interval of 2 months. Each
      patient was observed by a specialized nurse who scored the child's testing
      behavior with an observation grid, according to 45 items. After the first
      observation, children and adolescents were given feedback on the identified
      errors. The second observation allowed scoring the improvements. During the first
      observation, nearly 90% of the patients made 3 or more mistakes, 69% more than 5,
      and 10% more than 10. During the second observation, these frequencies fall to
      17, 2, and 0%. The main errors were the following (first vs second observation,
      in % of patients): not washing hands: 54 vs 3; incorrect setting for hour and
      date: 47 vs 2, and 17 vs 2; no knowledge of the meaning of "HI" (blood glucose >
      500 or 600 mg/dL): 55 vs 3; no knowledge of the meaning of "LO" (< 10 or 20
      mg/dL): 49 vs 1; insufficient blood drop: 19 vs 10. Younger children, with a
      shorter duration of diabetes and of autonomy for SMGB, need closer supervision.
      Errors were unrelated to frequency of SMBG, and glycated haemoglobin. To
      conclude, it is important to periodically assess diabetic children and
      adolescents' SMGB technique in order to correct the mistakes, mainly in younger
      children. The use of an observation grid allows an accurate analysis of the
      numerous possible errors.

PMID- 12806874
TI  - [Recent progress in the "fibrinogen hypothesis"].
AB  - Several clinical and epidemiological studies have demonstrated that a high level
      of plasma fibrinogen is an independent risk factor for coronary, cerebral and
      peripheral artery disease. The role of fibrinogen in cardiovascular diseases is
      mainly due to thrombotic complications in advanced stages of the atherothrombotic
      disease. However, fibrinogen also plays an active role in the initiation and
      development of atheromatous plaques. The relations between fibrinogen and
      ischemic cardiopathies, other vasculopathies and diabetes mellitus are discussed.
      The controversial effects of statins on fibrinogen are also described.

PMID- 12806875
TI  - [Review on hypertrophic osteoarthropathy and digital clubbing].
AB  - Clubbing was first described by Hippocrates more than 2.500 years ago. It may be
      seen alone or as part of an entity called hypertrophic osteoarthropathy which
      include periostitis, arthritis and sometimes thickening and edema of the skin
      around the affected joints. Pulmonary diseases such as cancer, abscess, empyema,
      bronchiectasis and cystic fibrosis are the major diseases known to be associate
      with hypertrophic osteoarthropathy. Digestive tract cancer, cyanogenic congenital
      heart disease are well known association. Many theories have attempted to explain
      the appearance of this sign but few have persisted. In this article, we review
      characteristics, relation with etiology and the basis of the pathophysiology of
      hypertrophic osteoarthropathy and particularly of clubbing.

PMID- 12806876
TI  - [H1 histamine antagonists].
AB  - Histamine is an important mediator for early phase allergic reactions that are
      involved in atopic diseases, mediated by specific IgE antibodies. After
      allergenic contact, its liberation induces unpleasant symptoms like itching,
      several manifestations as local vasodilatation, bronchoconstriction, mucus
      hypersecretion. Antagonists of H1 histamine receptors are the most prescribed
      drugs, due to their symptomatic effects at the levels of nasal or conjunctival
      mucosa, and the skin. Their major indications cover allergic rhinitis, either
      seasonal or perennial, and idiopathic chronic urticaria, as a first line
      medication. The pharmacological evolution allows to distinguish three generations
      of products differing at the levels of specificity, long acting period, and
      toxicity. The authors are discussing the respective benefits of two recent
      molecules presented as 3rd generation molecules: fexofenadine and levocetirizine,
      while repositioning their use among available treatment strategy.

PMID- 12806877
TI  - [Lower limb edema and steatorrhea: value of scintigraphic technics].
AB  - The authors report the case of a young woman with right lower limb edema who also
      presented one steatorrhea. Her clinical history is typical for one primary
      lymphedema and the lymphoscintigraphic investigation of the lower limbs confirms
      the diagnosis. The scan showed the absence of the right iliac and lomboaortic
      lymph nodes but also that the thoracic duct was normally present. One C14
      triolein breath test is pathological and proves the malabsorption of the fats.
      The authors discuss the interest of the scintigraphic techniques in such case and
      review the problem of the association between lower limb lymphedemas and fatty
      malabsorption.

PMID- 12806878
TI  - [Hemoglobinopathy C and splenomegaly in an Ivory Coast patient. Value of
      splenectomy].
AB  - We report the case of a young patient native of the Ivory Coast who suffered from
      homozygous hemoglobin C disease. He presented with the usual findings of this
      hemoglobinopathy: a moderate hemolytic anemia and a massive, painful and even
      disabling splenomegaly. Pain completely disappeared following splenectomy.
      However, postoperative course was complicated by portal venous thrombosis, which
      was medically treated. No deficiency of natural coagulation inhibitors could be
      demonstrated, so splenectomy was the only factor predisposing to thrombosis. We
      consider that in only very few cases of hemoglobin C disease, splenectomy
      (preceded by prophylactic antipneumococcic vaccine) may be indicated from pain
      and risk of spontaneous splenic rupture.

PMID- 12806879
TI  - [Image of the month. Ectopic carotid in the middle ear cavity].

PMID- 12806881
TI  - [In vitro fertilization: a quarter of a century later (part II)].

PMID- 12806882
TI  - The relationship between HIPAA's Privacy Rule and other federal laws.

PMID- 12806883
TI  - Canine X-linked muscular dystrophy in Japan (CXMDJ).
AB  - The purpose of this study was to develop a strain of canine X-linked muscular
      dystrophy (CXMD), a model of Duchenne muscular dystrophy, in Japan. A female
      beagle was artificially inseminated with frozen-thawed spermatozoa derived from
      an affected golden retriever. Subsequently, two carrier female dogs (G1 carriers)
      and four normal male littermates were produced. Thereafter, the two G1 carriers
      were mated with beagle sires. As a result, each bitch whelped three times, and
      out of 54 pups, 17 affected male descendants, and 11 carrier female descendants
      (G2 carriers) were detected. One G2 carrier was then mated with a beagle sire and
      15 pups in two whelpings were produced, including five affected males and four
      carrier females (G3 carriers). A total of 10 female beagles were artificially
      inseminated to evaluate the fertility of the frozen-thawed spermatozoa from the
      two affected dogs. The whelping rates of the two affected dogs were 4/5 and the
      litter sizes were 5.0 +/- 1.41 and 6.0 +/- 0.82, respectively. These results
      indicate that a canine X-linked muscular dystrophy colony has been established in
      Japan. We called them CXMDJ.

PMID- 12806885
TI  - Applications of recombinant Leishmania amazonensis expressing egfp or the beta
      galactosidase gene for drug screening and histopathological analysis.
AB  - Leishmania amazonensis recombinants expressing the enhanced green fluorescent
      protein (egfp) gene or beta-galactosidase gene (lacZ) were constructed for drug
      screening and histopathological analysis. The egfp or lacZ in a leishmanial
      transfection vector, p6.5, was introduced into L. amazonensis promastigotes, and
      egfp or lacZ-carrying recombinant L. amazonensis, La/egfp and La/lacZ,
      respectively, were obtained. Expression of egfp or lacZ in both promastigotes and
      amastigotes could be clearly visualized by fluorescence microscopy or by light
      microscopy with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal),
      respectively. Fluorescence signal and beta-galactosidase activity measured by a
      colorimetric reaction with chlorophenol red beta-D-galactopyranoside (CPRG) were
      well correlated to the numbers of these parasites. The inhibitory concentration
      (IC50) of a leishmanicidal drug, amphotericin B, in L. amazonensis promastigotes
      measured using La/egfp and La/lacZ was similar to that measured by conventional
      methods such as cell counting, thymidine incorporation and colorimetric assay.
      Furthermore, the fluorescence signal and absorbance of CPRG correlated well with
      the numbers of La/egfp and La/lacZ amastigotes in macrophages, respectively,
      suggesting La/egfp and La/lacZ can be a convenient and useful tool for drug
      screening not only in promastigotes, but also in amastigotes of L. amazonensis.
      La/lacZ collected from mouse tissues four weeks after the parasite infection were
      stained well with X-Gal. La/lacZ allowed parasite detection at high sensitivity
      in the tissues of infected mice and will be useful for following infections in
      macrophages in vivo. Thus, the marker-transfected Leishmania parasites
      constructed in this study will be useful for analyses of Leishmania parasites,
      especially at the intracellular stage.

PMID- 12806884
TI  - Physiological difference between dietary obesity-susceptible and obesity
      resistant Sprague Dawley rats in response to moderate high fat diet.
AB  - The primary aim of the present study was to define central and peripheral
      physiological differences between dietary obesity-susceptible (DOS) and obesity
      resistant (DOR) outbred Sprague Dawley (SD) rats when given a moderate high fat
      diet containing 32.34% of energy as a fat. After a 9-week feeding period, the DOS
      SD rats consumed significantly more feed (11.1%) and had higher abdominal (39.9%)
      and epididymal (27.5%) fat pads than the DOR-SD rats. In addition, serum leptin
      and insulin levels were significantly increased in the DOS-SD rats compared with
      those in the DOR-SD rats. However, we did not observe significant differences in
      serum triglyceride, cholesterol and glucose. No differences in hypothalamic OB-Ra
      and Rb mRNA expressions were found between the two groups. In contrast, arcuate
      NPY immunohistochemical expression was much higher in the DOS-SD rats than in the
      DOR-SD rats, though NPY expression in the supraoptic and paraventricular nuclei
      was not different between the two phenotypes. In peripheral tissues, the DOS-SD
      rats showed noticeably increased acetyl CoA carboxylase (ACC) mRNA expression in
      the liver, not epididymal fat. However, Western blot of peroxisomal proliferator
      activated factor gamma (PPAR gamma) in the liver and epididymal fat was not
      different between the two phenotypes of SD rats. It was concluded that different
      body weight phenotypes within outbred SD population responded differently to the
      development of dietary induced obesity via altered anabolic features in the
      hypothalamus and liver.

PMID- 12806886
TI  - Sendai virus vector-mediated gene transfer of glial cell line-derived
      neurotrophic factor prevents delayed neuronal death after transient global
      ischemia in gerbils.
AB  - We have developed a cytoplasmic replicating virus vector of Sendai virus (SeV)
      that infects and replicates in most mammalian cells, including neurons, and
      directs high-level gene expression. To investigate the protective effect of SeV
      vector-mediated gene transfer of glial cell line-derived neurotrophic factor
      (GDNF) on the delayed neuronal death caused by transient global ischemia in
      gerbils, SeV vectors carrying either GDNF (SeV/GDNF) or enhanced green
      fluorescent protein gene (SeV/GFP) were stereotaxically microinjected into the
      lateral ventricle. Four days after injection, occlusion of the bilateral common
      carotid arteries for 5 min produced transient global forebrain ischemia.
      Treatment with SeV/GDNF significantly decreased the delayed neuronal death of the
      hippocampal CA1 pyramidal neurons observed 6 days after the operation. TUNEL
      staining demonstrated that SeV/GDNF treatment markedly reduced the number of
      apoptotic cells in the hippocampal CA1 neurons, indicating that SeV/GDNF
      treatment prevented apoptosis. Furthermore, delayed neuronal death on the
      contralateral side of the hippocampal CA1 was also prevented to a similar extent
      as that on the ipsilateral side. These results suggest that SeV/GDNF prevents the
      delayed neuronal death induced by ischemia and is potentially useful for gene
      therapy for stroke.

PMID- 12806887
TI  - Molecular cloning of ELOVL4 gene from cynomolgus monkey (Macaca fascicularis).
AB  - ELOVL4, elongation factor of very long chain fatty acids-4, is known to be
      responsible for autosomal dominant macular degeneration and Stargardt-like
      macular degeneration. In this study, we cloned the monkey homologue of ELOVL4 and
      determined the cellular and tissue distribution of the gene product. Sequence
      analysis of the monkey ELOVL4 gene revealed a high degree of homology between
      human and monkey. The cloned full-length cDNA of monkey ELOVL4 encoded 314 amino
      acids, the same length as human and two amino acids longer than mouse. The monkey
      ELOVL4 conserved the characteristics typical of the super family of ELO enzymes
      involved in the metabolism of membrane-bound fatty acid elongation. Real-time
      quantitative PCR demonstrated that the monkey ELOVL4 gene was highly expressed in
      restricted tissue-specific fashion, not only in the retina but also in the skin
      (90% of retina) and thymus (111% of retina). Immunohistochemical analysis
      detected signals predominantly in the photoreceptor layer of the monkey retina.

PMID- 12806888
TI  - Ratio of leptin to adiponectin as an obesity index of cynomolgus monkeys (Macaca
      fascicularis).
AB  - Obesity is responsible for inducing various metabolic diseases. Laboratory-bred
      cynomolgus monkeys exhibit spontaneous onset of obesity. However, to date, no
      blood chemistry index to identify the state of obesity in cynomolgus monkeys has
      been determined. In the present study, to determine such an index, we measured
      the serum levels of two adipocyte-derived hormones, leptin and adiponectin, and
      evaluated the relationship between these hormones and other serum energy
      metabolic factors (i.e. insulin, total protein, glucose, total cholesterol and
      triglyceride) as well as the percentage of body fat (%Fat) in mature cynomolgus
      monkeys. Both in females and males, leptin was positively correlated with insulin
      and %Fat, and adiponectin was negatively correlated with insulin and %Fat. In
      female cynomolgus monkeys, leptin, adiponectin, and glucose were selected as the
      most important determinants for %Fat in multiple regression analysis, and in male
      cynomolgus monkeys, leptin was selected. The ratio of leptin to adiponectin (L/A
      ratio) was significantly elevated in the animals with %Fat over 40 (P < 0.01).
      The results indicate that L/A ratio is a potential index for comprehensively
      identifying obesity in cynomolgus monkeys.

PMID- 12806889
TI  - Evaluation of a forced-air-ventilated micro-isolation system for protection of
      mice against Pasteurella pneumotropica.
AB  - Studies to date have established that the physical environment inside cages can
      be controlled adequately by setting the intra-cage ventilation at 60 air changes
      per hour in a forced-air-ventilated micro-isolation system (FVMIS). In this
      study, the capability of FVMIS to prevent inter-cage transmission of
      microorganisms was evaluated using Pasteurella pneumotropica as a reference
      microorganism. One FVMIS rack and a conventional rack were used, and cages with
      mice positive for P. pneumotropica and those with P. pneumotropica-free mice were
      housed on both racks. The mice were examined for P. pneumotropica contamination
      every 4 weeks after initiating the experiment for 12 weeks using a polymerase
      chain reaction method. Some P. pneumotropica-free mice housed in open air cages
      in the conventional rack became positive for P. pneumotropica (four of 28 animals
      after 4 weeks; eight of 28 animals after 12 weeks), but all P. pneumotropica-free
      mice housed in the FVMIS cages remained negative for the bacterium throughout the
      experiment. The results demonstrate that FVMIS can prevent inter-cage
      transmission of P. pneumotropica when proper cage handling practice is under
      taken.

PMID- 12806890
TI  - Developmental expression of penile reflexes and copulatory behavior in male rats.
AB  - First, pubertal development of the penile reflexes, e.g., erections, cups and
      flips in Wistar-Imamichi male rats was investigated following sheath retraction.
      Second, the penile reflexes and copulatory behavior in the above males were
      compared between 10 and 44 weeks of age. The penile reflexes in Wistar-Imamichi
      rats began to appear from day 26, and all males displayed full components of the
      reflexes on day 47. The occurrence rates and mean numbers of erections, cups and
      flips in aged adults were significantly low, compared with the young adults.
      Also, in the observation of copulatory behavior the occurrence rate of
      ejaculations, and mean numbers of intromissions and ejaculations in aged adults
      were significantly lower than that in young adults. These results of the present
      study may suggest that the decrease of copulatory behavior in male rats with age
      results from the dysfunction of the penile reflexes with age.

PMID- 12806891
TI  - Giant lysosomes in the renal proximal tubules--a morphological characteristic of
      DBA/2 and DBA/1 mouse kidneys.
AB  - The DBA/2Cr mouse is characterized by the presence of giant lysosomes located in
      the proximal convoluted tubules of males and proximal straight tubules of
      females. However, it remains unclear whether these giant lysosomes in the
      proximal tubules are characteristic of DBA/2Cr specifically, or are common to
      other DBA/2 substrains and DBA/1. The present study investigated the morphology
      of kidneys from DBA/2CrSlc, DBA/2JJcl, DBA/2NCrj and DBA/1JNCrj mice of both
      sexes. Giant lysosomes in the renal proximal tubules were found to represent
      common morphological characteristic of both DBA/2 and DBA/1JN.

PMID- 12806892
TI  - Spontaneous cerebellar dysplasias in BrlHan: WIST@Jcl rats.
AB  - Focal disturbed laminar architecture in cerebellar vermis was observed in 25 out
      of 100 (25%) males, and 25 out of 100 (25%) females of BrlHan: WIST@Jcl rats. The
      cortical molecular and granular layers were haphazardly distributed around the
      primary and/or secondary fissures. The stellate and basket cells positively
      stained with parvalbumin immunohistochemistry were observed exclusively in the
      separated molecular layer. Purkinje cells were found at the boundary between the
      molecular and the granular layers. Glial fibrillary acid protein (GFAP)
      immunohistochemistry revealed disarranged fibers of the Bergman glial cells.
      Based on the incidence of this spontaneous cerebellar lesion, it was presumed to
      be related to certain genetic factors of this rat strain.

PMID- 12806893
TI  - Newly established low seizure susceptible and seizure-prone inbred strains of
      Mongolian gerbil.
AB  - Two inbred strains of the Mongolian gerbil with different phenotypes in seizure
      behaviour and coat color were newly established. LSAG/Nu has low seizure
      susceptibility and albino phenotypes, whereas SPBG/Nu has seizure-prone and black
      coat color phenotypes. LSAG was compared with SPBG as to seizure incidence and
      grade. Mean ages at seizure onset of LSAG and SPBG were 6 and 3 months,
      respectively. Seizure incidences in over 9 months old LSAG and SPBG gerbils were
      37.3% (66/177) and 95.2% (118/124), respectively. LSAG has a significantly lower
      incidence (p < 0.001) and grade (p < 0.001) of seizures than SPBG. Only a few
      seizing LSAG gerbils exhibited myoclonus to tonic-clonic seizure progression.
      These results suggest that LSAG has some mechanisms which delay the onset of
      seizures and prevent them from becoming serious. Both strains of gerbils can be
      expected to be useful animal models for the study of human idiopathic generalized
      epilepsy.

PMID- 12806894
TI  - Life span and spontaneous tumors incidence of the Wistar Mishima (WM/MsNrs) rat.
AB  - The life spans and spontaneous tumors in a total of 1960 Wistar Mishima
      (WM/MsNrs) rats, inbred strain, from the 80-130th generations were examined. The
      average life span (mean +/- SD) was 731 +/- 173 days (n = 1053) in the males and
      813 +/- 214 days (n = 907) in the females (p < 0.0001). The average life span of
      tumor-afflicted females was significantly longer than that of the non-tumor group
      (p < 0.0001), while no such difference was observed in males. Tumors were
      observed in 33 males (3.1%) and 246 females (27.1%). In the males, tumors were
      often observed under the skin (2.2%). Frequencies of tumors in lung and liver,
      bones and intestine were less than 0.5%. In the females, incidence of mammary
      tumor was 20.1%, and various organs such as ovaries, uterus, bones, lung, and
      liver had tumor incidence frequencies of less than 3.5%. It was concluded that
      WM/MsNrs rats might be suitable for life span and age-related studies because of
      their characteristics of length of longevity and the low incidence of spontaneous
      tumors in both sexes.

PMID- 12806895
TI  - Evaluation of developmental competence of vitrified-warmed early cleavage stage
      embryos and their application for chimeric mouse production.
AB  - The developmental competence of in vitro cultured embryos vitrified-warmed at an
      early cleavage stage (2- or 4, 8-cell stage) was examined by both direct transfer
      into recipient animals and after in vitro manipulation for chimeric mice
      production using embryonic stem (ES) cells. Vitrified-warmed embryos transferred
      at the morulae and blastocyst stages showed fetus development comparable to
      control embryos, although blastocyst development of vitrified-warmed embryos was
      significantly slower than that of controls. When vitrified-warmed early cleavage
      stage embryos were used for chimeric mouse production using ES cells, 1 to 10% of
      the injected or aggregated embryos developed into chimeric neonates and germ-line
      chimeric mice were obtained from all ES cell lines. This study indicates that
      embryos developed in vitro from vitrified-warmed embryos have equivalent
      competence with unvitrified embryos irrespective of stage of vitrification and
      that these vitrified-warmed embryos maintain adequate viability even after in
      vitro manipulation such as aggregation and microinjection with ES cells.

PMID- 12806896
TI  - [Early detection of mild cognitive impairment, dementia, and depression in the
      aged and the therapeutic strategy].

PMID- 12806897
TI  - Mild cognitive impairment: making headway by stepping backwards.
AB  - Mild cognitive impairment (MCI) is a prevalent medical problem and the concept
      and term have become a catch-phrase for research and clinical practice. However,
      little is known about the most effective tools for a clinical diagnosis of MCI,
      its potential significance for individual patients and the best possible
      intervention--at least as long as MCI is considered as a diagnostic entity. We
      propose a simplified diagnostic and interventional algorithm for the detection
      and management of patients with MCI. We argue that MCI is so important, because
      it represents the closest call for an identification of treatable diseases or
      risk factors before the final manifestation of irreversible brain changes.
      Stepping backward by focussing on underlying disease processes and attempting
      causal interventions must be preferred to a mere symptomatic treatment of MCI as
      a preclinical form of Alzheimer's disease.

PMID- 12806898
TI  - [The prevalence of mild cognitive impairment (MCI) among the community-dwelling
      elderly: findings from the 2nd Nakayama study].
AB  - To determine the prevalence of Mild Cognitive Impairment (MCI) in community
      dwelling elderly, a door to door population survey was carried out on all persons
      aged 65 years and older residing at home on the prevalence day (1 August 1999).
      All assessments were conducted by neuropsychiatrists. The diagnosis was made with
      the Geriatric Mental State (GMS)--Automated Geriatric Examination for Computed
      Assisted Taxonomy (AGECAT) (Copeland et al, 1986). AGECAT organicity levels 1 and
      2 (sub-cases) are referred to as MCI. Of 1461 inhabitants, 1156 (79.1%) completed
      the protocol. The prevalence of MCI was 5.3%, with 1.7% organic brain syndrome
      level 2 and 3.6% organic brain syndrome level 1. MCI is associated with an
      increased risk of developing dementia. However, research on the prevalence of MCI
      has produced inconsistent data. The operational consensus criteria of MCI should
      be established for future community-based longitudinal study.

PMID- 12806899
TI  - [Biological markers for Alzheimer disease].
AB  - The development of diagnostic markers for earlier and more reliable diagnosis of
      Alzheimer disease (AD) is essential, particularly because therapeutic medication
      is available for AD. Cerebrospinal fluid (CSF) is a useful source of diagnostic
      information. Previously we found the increase of total tau protein in CSF in
      normal pressure hydrocephalus patients, and others reported the increase also in
      corticobasal degeneration and frontotemporal dementia. To differentiate the AD
      from other diseases, further approach was employed and oxidized protein in CSF
      was investigated. Heat stable fractions of CSF were analyzed on the content of
      carbonyl residues, which are derivatives of protein oxidization. The result
      suggests that protein oxidation is highly involved in AD and that this method
      might be useful to differentiate AD from other neurological disease.

PMID- 12806900
TI  - [The measurement of phosphorylated tau in human cerebrospinal fluid as a
      diagnostic marker for Alzheimer's disease].
AB  - We examined total 570 cerebrospinal fluid (CSF) samples from a variety of
      diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and
      nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels
      of tau protein phosphorylated at serine 199 (CSF/p-tau199) by a recently
      established sandwich ELISA. The CSF/p-tau199 levels in the AD group were
      significantly elevated compared to those in all the other non-AD groups. Receiver
      operating characteristics curves showed that the diagnostic sensitivity and
      specificity for the AD group vs all the other non-AD group using the CSF/p-tau199
      were 85. 2% and 85.0%, respectively. Although there was a significant positive
      correlation between CSF/p-tau199 and CSF total tau (CSF/t-tau) levels in the AD
      group, CSF/p-tau199 classifies patients with AD and other disorders more
      accurately than the CSF/t-tau. Our study suggests that CSF/p-tau199 testing will
      help in supporting antemortem diagnosis of AD and in conducting emerging
      therapies that should be based on an accurate detection of AD while patients are
      alive.

PMID- 12806901
TI  - [The dentate gyrus neurogenesis: a common therapeutic target for Alzheimer
      disease and senile depression?].
AB  - Neurogenesis persistently occurs even in the adult dentate gyrus. Since most of
      the anti-depression therapies increase adult neurogenesis, suppressed
      neurogenesis has been proposed to be one of the candidate etiologies of
      depression. Here we show that Cerebrolysin, an anti-dementia drug that improves
      the activity of daily living of Alzheimer disease (AD) patients, can enhance
      neurogenesis and spatial learning of adult female rats. Regarding the anatomical
      importance of the dentate gyrus in AD pathogenesis and the frequent association
      of depressive symptoms in preclinical phase of AD, our finding suggests a
      possibility that AD involves suppressed neurogenesis causing the decreased
      activity of daily living. Pseudodementia might also involve suppressed
      neurogenesis but differ form AD since the neurodegenerative process in AD may be
      irreversible.

PMID- 12806902
TI  - [Genetics of epilepsy].
AB  - Epilepsy is a common neurological disease and encompasses a variety of disorders
      with paroxysms. Although there is a genetic component in the pathogenesis of
      epilepsy, the molecular mechanisms of this syndrome remain poorly understood. The
      identification of genes responsible for human epilepsy was first documented in
      progressive myoclonic epilepsy (EPM) because of their clear inheritance and
      phenotypic presentation. EPM is characterized by frequent myoclonic jerks and
      cumulative neurological deterioration and includes MERRF, a mitochondrial disease
      and DRPLA, a triplet disorder. The genes responsible for EPM seem to participate
      in the maintenance of cell viability. Genetic defects have been recently
      identified also for some familial epilepsy in which the phenotypes are similar to
      common idiopathic epilepsies. Defects of neuronal nicotinic acetylcholine
      receptor, a ligand-gated ion channel, caused nocturnal frontal lobe epilepsy.
      Mutations of two K(+)-channel genes were identified in benign familial neonatal
      convulsions. Mutations in the voltage-gated Na(+)-channel alpha 1, 2 and beta 1
      and the GABAA receptor gamma 2 subunit genes were found as a cause of dominant
      epilepsy with febrile seizures plus, a clinical subset of febrile seizures.
      Abnormalities of Na(+)-channel alpha 1 subunit were also associated with severe
      myoclonic epilepsy in infancy. Other genes encoding ion channels expressed in the
      brain were also found to be associated with other familial epilepsy. This line of
      evidence suggests the involvement of channels expressed in the brain in the
      pathogenesis of certain idiopathic epilepsy, albeit there are a few exceptions
      that abnormalities of non-channel molecules have been found to be associated with
      idiopathic epilepsy.

PMID- 12806903
TI  - [Use of functional MRI in epilepsy].
AB  - For the purpose of examining pathophysiological mechanisms of a memory function
      in epileptic patients or an utility of fMRI for a presurgical assessment in
      neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or
      visual memory task were investigated in patient group of temporal lobe epilepsy
      and normal subject group. Patient group of temporal lobe epilepsy consisted of 7
      cases, of which 3 and 3 cases had left and right temporal foci, respectively,
      except 1 case having undetermined laterality of temporal foci. Normal subjects
      were 16 cases. All the epileptic and normal subjects were right-handed except for
      1 lefty normal subject. Verbal memory tasks were composed of covert and overt
      recall tasks of 10 words given auditorily, while visual ones were recall tasks of
      6 figures given visually. Eventually, in normal subjects, the left side-dominant
      medial frontal lobes including the superior frontal and anterior cingulate gyri
      were mainly activated in fMRI during the covert recall tasks of verbal memory,
      while the left side-dominant inferior frontal and precentral gyri as the motor
      language areas were chiefly activated in addition to the medial frontal lobe
      during the overt recall tasks. Further, the bilateral occipital lobes were
      activated in fMRI during the recall tasks of visual memory. Also in patient
      groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks
      were the same as in normal subject group, regardless of the laterality of
      epileptic temporal foci. These results suggest that fMRI is useful for the
      determination of the lateralization of the cerebral hemisphere contributing to
      verbal memory function and therefore for the presurgical assessment of memory
      function in neurosurgical treatment of epilepsy.

PMID- 12806905
TI  - Psychosis and epilepsy: a neurologist's perspective.
AB  - Epilepsy and psychosis are diseases of the brain which cause considerable impact
      on quality of life particularly when they occur in the same individual. This
      review comments on postictal psychosis, chronic schizophrenia like psychosis in
      epilepsy, and the psychoses related to the treatment of epilepsy with
      antiepileptic drugs and surgery. Possible mechanisms of psychosis including the
      concept of forced normalization and dopaminergic overactivity in the mesolimbic
      system are discussed.

PMID- 12806904
TI  - [Application of synthetic aperture magnetometry for epilepsy surgery].
AB  - Recently developed synthetic aperture magnetometry (SAM) is a new MEG signal
      analysis introducing a high performance spatial filtering technique. SAM is not
      an inverse solution like dipole analysis, but rather an adaptive beamformer for
      estimating source activity at each selected voxel inside of the brain. SAM can
      estimate source changes as a function of time, or power changes subjected to
      statistical analysis from the non-averaged raw MEG data. Thus this method enables
      to display the regional currentodensitogram of the arbitrary selected brain
      tissue as if depth electrodes were inserted (SAM virtual sensor), and to detect
      the origin of epileptic discharges and their spread. By applying statistical
      discrimination, SAM can also demonstrate the spatial distribution of event
      related changes of brain rhythm (SAM statistical method), in other words
      activated cerebral cortex during task performance. We will present the usefulness
      of noninvasive SAM methods in epilepsy surgery detecting the epileptogenic zone
      by SAM virtual sensor method as well as eloquent brain by SAM statistical method.

PMID- 12806906
TI  - Recent advances in the psychopharmacology of psychosomatic medicine.

PMID- 12806907
TI  - [The medicine of nurturing life energy--health creation and self-organization].
AB  - It is reality that human's body and mind are being created by life energy through
      every moment of life. As modern medicine does not consider this life energy
      itself, the most modern people hardly does not think it's intuitive meaning and
      use it to actualize their health and happiness in life. They can consider the
      outcome of life phenomena in the fields of physical, psychological, sociological
      and ethical sides, but they can not ask what life energy is, and subsequently can
      not use it in their life. Therefore, they live to make effort to actualize how to
      change life style considering of medical scientific facts (Evidence-Based-Medical
      Health Care). The intuitive life's action which can contact with the outer
      worlds, has the dynamic relationship with them and it creates new body and mind
      continuously. Modern medicine has not researched this dynamic life energy itself.
      What has life energy, single gene, single cell, single organ such as the brain
      and heart and single human beings, have been maintained their life by using their
      common and universal two life energies which are called self-organization, self
      creativity and communicative ability. These two life energies of them were
      communicating with themselves or each others and their environments, and
      recreating their form and function continuously every moment of lives. It was
      conceptualized "Body-Mind-Spirit (Life-energy)-Life Dynamics". All of life
      phenomena which are not only diseases but also health, come from the results of
      "Body-Mind-Spirit-Life Dynamics". When we communicate with the outer worlds in
      "Real Self", human beings will keep the highest state of "Body-Mind-Spirit-Life
      Dynamics". We clarified that human beings can actualize the healthy and happy
      lives by themselves from understanding this idea, it also means for them to be
      able to create healthy personality through their lives and we clarified new
      assessment way of life energy simultaneously.

PMID- 12806908
TI  - [A study of logotherapy for chronic low back pain patients].
AB  - DHEA-S (dehydroepiandrosterone sulfate) has many roles in human body as
      comprehensive vital power, whose metabolite is urine 17-KS-S (abbreviated S),
      having function of anti-cortisol. The metabolite of cortisol is urine 17-OHCS
      (abbreviated OH). DHEA-S is produced not only in adrenal glands but in brain. In
      order to examine the effects of logotherapy, urine S and OH were examined.
      Subjects were chronic low back pain patients treated by loxoprofen sodium
      (NSAID). In Group 1 (n = 11) logotherapy was not added, but in Group 2 (n = 10)
      it was added. Before the treatment, both groups showed low S and high OH. After 3
      weeks, Group 2 showed higher S and lower OH than Group 1. After 18 weeks, 4 cases
      (40%) were relapsed in Group 2, and 10 (90.9%) were in Group 1 (p < 0.05). Group
      2 was divided into 2 groups; relapsed group (n = 4) and non-relapsed group (n =
      6). S, OH, S/OH were examined between 2 groups of Group 2 and Group 1. Relapsed
      group of Group 2 and Group 1 showed lower S and higher OH than non-relapsed group
      of Group 2. [Discussion] Logotherapy is a method to activate comprehensive human
      vital power. This is the mechanism through stimulating and activating human brain
      function.

PMID- 12806909
TI  - [A study of psychoneuroendocrinological effects of music therapy].
AB  - The objective evaluation of Psychoneuroendocrinological effects of music is
      performed in listening and performing. Subjects were classified into 3 groups; a
      control group and performance/listening groups voluntarily in each 10 subjects.
      Urine 17-KS-S (abbreviated S) and 17-OHCS (abbreviated OH) were measured before
      (phase I), after the experiments (phase II) and on the following morning (phase
      III). They enjoyed listening to their favorite music by stereo sets or performing
      favorite music instruments. No directions were done on the quality of music. OH
      showed decreasing effects in both control and performance/listening groups. S
      showed significant increase in listening group. From a rise of S/OH a wear and
      tear by stress and a skewness of balance of restoration were corrected. Music is
      considered that it contributed to relaxation from stress and a wear and tear by
      the stress and correction of balance of restoration. The fact that the efficacy
      persisted until the morning of the following day indicates the efficacy persists
      for a relatively long period of time.

PMID- 12806910
TI  - [Clinical factors related to gains in body mass index (BMI) among patients under
      long-term antipsychotic treatment].
AB  - OBJECTIVE: Weight gain and obesity are often seen among patients taking
      antipsychotic drugs, the incidence being higher in this group than among the
      general adult population. They constitute risk factors for other diseases, such
      as hyperlipidemia, type 2 diabetes mellitus and hypertension, and may also
      adversely affect a patient's compliance. Thus the control of weight gain and
      obesity is significantly related to the quality of life for those who are under
      long-term antipsychotic treatment. We therefore conducted a retrospective
      investigation on the process of BMI increase in patients treated with
      antipsychotic agents over an extended period. The BMI of these patients was
      compared with measurements in the general adult population and the clinically
      relevant factors contributing to weight gain were identified. METHOD: The
      subjects were 66 outpatients (35 males, 31 females; mean age 37.5 +/- 11.9 y.o.,
      range 15-65 years) who satisfied the F2 category of the ICD-10 diagnostic
      criteria, and who were on antipsychotic drugs for more than 2 years and less than
      15 years. The study was conducted at two psychiatric clinics between May 1, 2000
      and June 1, 2001. The results of the survey were analyzed as follows: 1) The BMI
      of the subjects was compared against that of the controls who visited the Health
      Center, the Jikei Hospital from 1999 to 2002 to observe time-related trends over
      the study period; and 2) The odds ratio was computed using a logistic regression
      model with the mean of the changes in BMI during treatment as a dependent
      variable and clinically related factors, gender, age, diagnosis, clinical
      outcome, duration of treatment, baseline BMI, and type and dose of antipsychotic
      drugs as independent variables, to determine those factors contributing to the
      gain in BMI. RESULTS: 1) When the patients' ages were stratified, there were no
      significant differences between the male patients and the corresponding standard,
      either for the baseline or recent BMI at each age level, with the exception of
      the 15-39 age level. Among female patients, there were no significant differences
      for the baseline BMI at any age level. However, the recent BMI for them was
      significantly higher at all age levels. 2) In the study of factors related to
      increase in BMI, 3 factors--gender, age, and complete remission in clinical
      outcome--were found to have significant difference. The odds ratio was
      significantly higher in the female subjects (4.94; 95% CI: 1.42-17.27) and
      significantly lower in older subjects (0.93; 95% CI: 0.88-0.99), and in those
      subjects who were in complete remission (0.081; 95% CI: 0.007-0.954). No other
      factors produced statistically significant differences. DISCUSSION: 1) Gender,
      age, and clinical outcome were the independent factors that contributed to the
      increase in BMI for those patients under long-term antipsychotic treatment. 2)
      The gain in BMI was greater in female patients than in male patients. 3) Age was
      inversely related to the gain in BMI, therefore special care must be taken after
      administering antipsychotic drugs because younger patients may gain excessive
      weight and develop weight-related complications at an earlier stage. 4) The
      increase in BMI was minimal for patients in complete remission, suggesting that
      these patients were better adapted socially and aware of maintaining an optimum
      BMI. In planning antipsychotic treatment for each patient, not only its efficacy
      on psychiatric symptoms but also the risks--such as an increase in BMI--should be
      taken into consideration.

PMID- 12806912
TI  - [Frequency of apoptotic cells and BAX positive cells in the lymph nodes of
      colorectal cancer patients with metastasis and micrometastasis].
AB  - It is regarded that the presence of micrometastatic(isolated) cancer cells is a
      forerunner of metastasis. We classified advanced colorectal cancers into 3 groups
      such as metastasis group in which distinct metastasis was identified in lymph
      nodes by HE stain, micrometastasis group which was negative for metastasis by HE
      stain but positive for micrometastasis by immunostain using antibody for
      cytokeratin, and non-metastasis group which was negative for both stains. We
      investigated proliferative activity of cells and frequency of apoptotic cells in
      the lymph nodes from each group. The frequency of apoptotic cells in the
      metastasis group was significantly lower than the other groups (p < 0.02), and
      correlated with expression of BAX protein. In conclusion, frequencies of
      apoptotic cells and BAX positive cells in the nodes of metastasis group were
      significantly lower than micrometastasis group. And it was suggested that those
      changes were correlated with inflow of isolated cancer cells and formation of
      metastatic foci in the lymph nodes, and may reflected the difference of
      immunological activity against cancer cells.

PMID- 12806911
TI  - [Quantification of urinary hemoglobin by an immunological method].
AB  - The quantification method of urinary hemoglobin has not been established. We
      examined whether a reagent (Eiken, Tokyo) used to immunologically assay fecal
      hemoglobin could be utilized to quantify urinary hemoglobin. The coefficients of
      variation were 2.2-3.0% in the reproducibility of one-run assays using urine and
      4.3-5.7% in that of multiple-run assays using the standard sample of hemoglobin.
      Urinary hemoglobin was unstable and decreased in a time- and temperature
      dependent manner. However, addition of the hemoglobin stabilization buffer (50 mM
      phosphate buffer, pH 6.4) (Eiken) to urine made urinary hemoglobin stable.
      Urinary hemoglobin levels did not change significantly when stored at 4 degrees C
      for 7 days or at -80 degrees C for 30 days. The hemoglobin concentration (mean +/
      SD) of urine showing 1+, 2+ and 3+ with a test strip was 385 +/- 165(n = 30),
      1070 +/- 499(n = 40) and 4130 +/- 2770 ng/ml (n = 20), respectively. Urinary
      hemoglobin did not correlate with urinary albumin, transferrin, immunoglobulin G,
      N-acetyl-beta-D-glucosaminidase nor alpha 1 microglobulin. These results suggest
      that this immunological method using the hemoglobin stabilization buffer can be
      utilized for quantification of urinary hemoglobin, which may provide clinically
      important information.

PMID- 12806913
TI  - [The Autonomic Nervous Activity in Patients with Essential Hypertension who
      Showed Early Morning Rise of Blood Pressure].
AB  - Autonomic nervous function was evaluated by means of power spectral analysis of  
      heart rate variability in patients with essential hypertension who showed early
      morning rise of blood pressure (BP). We monitored ambulatory (BP) and physical
      activity in 80 untreated patients using TM 2425 (A&D Co.Ltd.). Early morning rise
      of  BP was defined a patient's blood pressure obtained between 6:00 to 9:00am is
      170mmHg or higher. Patients who showed early morning rise of BP were categorized
      into groups. Twenty patients, whose mean BP obtained between 6:00 to 9:00am were 
      higher than those obtained between 3:00 to 600am by 30mmHg or more, were defined
      as a surge type. Sixty patients, in whom the difference in BP was less than
      30mmHg, were defined as a sustained type. Power spectral analysis of   hourly R-R
      intervals for 24 hours was performed to obtain the low frequency power (LF, 0.04
      to 0.15 Hz) and high frequency power (HF, 0.15 to0.04 Hz).  LFn and LF/HF ratio
      were considered to  be indexes of sympathetic nervous activity, and HF
      parasympathetic nervous activity, respectively. Between 3:00 to 6:00am, LFn and
      LF/HF were  significantly higher and HF was significantly lower in the sustained 
      type patients than in the surge type patients. LF/HF and LFn in the surge type
      elevated  significantly beween 6:00 to 9:00am. These results indicate that both
      the loss of nocturnal decline in BP in the sustained type and the morning rise in
      BP in the surge type to occurred in association with changes in autonomic nervous
      system.

PMID- 12806914
TI  - [A case of hyperlipoproteinemia caused by corticosteroid therapy in a child with
      subacute necrotizing lymphadenitis].
AB  - A 10-year-old child was diagnosed as subacute necrotizing lymphadenitis. After a
      steroid hormone (predonine) administration for 17 days, he showed total
      cholesterol(TC) 420 mg/dl, triglyceride(TG) 839 mg/dl, and LDL-cholesterol 241
      mg/dl. The hyperlipidemia seemed to be a side effect of the steroid at the onset.
      However, the lipoprotein fraction by the agarose gel and polyacrylamide gel (PAG)
      electrophoresis showed type III of the WHO classification, that is, presence of
      broad band as well as appearance of mid band, small dense-LDL and the disrupted
      type of LDL band. In addition, there were hyperlipidemia (high levels of the TC,
      TG, LDL-cholesterol) in 4 persons out of 6 family members, and LDL pattern of the
      PAG electrophoresis, 4 persons showed the nodular type. They have higher
      possibility of combined-type familial hyperlipiemia from the above results, and
      it seemed to be the case in which the hyperlipidemia was exacerbated by the
      steroid administration.

PMID- 12806915
TI  - [Past, present and future of external quality assessment of medical laboratory
      testing in Japan].
AB  - In Japan, three major bodies have conducted external quality surveillance of
      medical laboratory performance: the Japan Medical Association, the Japan
      Association of Medical Technologists, and the Japan Society of Registered Medical
      Laboratories. Although these systems are working very well to elevate the quality
      of laboratory tests, each has adopted its own surveillance system with little
      communication. All of these surveillance systems have problems in the evaluation
      of laboratory proficiency. Thus, the 3 bodies should be unified first to
      establish an efficient National External Quality Assurance Scheme. New IT
      technology should also be introduced into the system in the future.

PMID- 12806916
TI  - [Possibility of the evaluation by Target Value--Clinical Chemistry Examination].
AB  - In the evaluation of external quality control survey, the mean value of peer
      group has been using as the target value generally. However, there are some
      arguments about whether the mean value shows the true value of survey sample. In
      1992 National Federation of Industrial Health Organization(NFIHO) established the
      committee for reference target value and studied the determining of reference
      target value. In 1993 NFIHO started the evaluation by the reference target value
      determined by the committee. In 1996 committee for external quality control
      survey of Japan Medical Association (JMA) started the evaluation by adjusted mean
      value of peer group. In 1999 JMA established the sub-committee for target value
      and published the study report in 2000. By using the result from the above two
      associations, I have studied the possibility of the evaluation by target value. I
      concluded as follows. 1) The good agreement was seen between the target values
      and the mean value of peer group. 2) The poor agreements were seen in some
      anaytes. 3) By increasing the number of laboratory in which the traceability is
      being confirmed, the better agreement will come to be seen between the target
      value and the mean. 4) To determine the target value, we need the long-term
      maintenance of laboratory performance and the consumption of large energy. 5) As
      for the analyte, which is possible to calibrate by reference measurement
      procedure and reference material, the mean value after the traceability was
      confirmed can be used as the target value.

PMID- 12806917
TI  - [Control of accuracy of immunoserological laboratory data on medical network and
      standardization].
AB  - Construction of a medical network for each region and organization has become
      possible by utilization of information technology. Standardization of the data on
      the medical network is urgent. Especially, the standardization of
      immunoserological data is much delayed. In this study, the possibility of
      standardization of such data was reconsidered based on the findings from various
      control surveys. Regarding the measurement items for serum concentrations of
      proteins and other compounds, we concluded that standardization should occur in a
      manner similar to the method for standardization of biochemical data and accurate
      control. The data on CRP, IgG, IgA, IgM and AFP, which are determined using the
      respective standard compound, were converged to a range with inter-facility
      differences of less than 10% CV. The data on CEA were also converged to achieve
      an inter-facility difference of less than 10% CV through repeated survey.
      Automatic measurement for the markers of infection diseases has progressed, and
      the expression of measurements was changed to the absolute value of COI, U/ml or
      IU/ml although it was titer in the past. Since these expressions now coexist, it
      is impossible to standardize the data with absolute qualitative values. It seemed
      necessary to present them uniformly with qualitative or clinical criteria values
      or express the presence or absence of infection by a combination of related
      markers. The measurements obtained from autoantibody-related tests using
      identical reagent were found coincident, but measurements obtained using
      different reagents were discrepant and the differences were greater than the
      sensitivity of measurement. In immunoserological testing and immunochemical
      testing, it is most important whether the antigen/antibody used as the reagent is
      the same preparation or not. Therefore, the test should be reconsidered through
      setting a certain restrictions on each recognition site of epitope and antibody.
      Thus, we concluded that use of a suitable standard substance is effective for
      standardization of immunological data.

PMID- 12806918
TI  - [Laboratory accreditation and proficiency testing].
AB  - ISO/TC 212 covering clinical laboratory testing and in vitro diagnostic test
      systems will issue the international standard for medical laboratory quality and
      competence requirements, ISO 15189. This standard is based on the ISO/IEC 17025,
      general requirements for competence of testing and calibration laboratories and
      ISO 9001, quality management systems-requirements. Clinical laboratory services
      are essential to patient care and therefore should be available to meet the needs
      of all patients and clinical personnel responsible for human health care. If a
      laboratory seeks accreditation, it should select an accreditation body that
      operates according to this international standard and in a manner which takes
      into account the particular requirements of clinical laboratories. Proficiency
      testing should be available to evaluate the calibration laboratories and
      reference measurement laboratories in clinical medicine. Reference measurement
      procedures should be of precise and the analytical principle of measurement
      applied should ensure reliability. We should be prepared to establish a quality
      management system and proficiency testing in clinical laboratories.

PMID- 12806919
TI  - [Issue of education system for the medical technologist students and vision for
      the future].
AB  - In April 2000, education programs for student medical technologist has been
      revised considerably, with main thought of free-will programs at every
      educational facilities. Guideline for the state examination questions were
      published in June 2002 in related to above matter. These principles of
      educational programs are considered to be much effective in remarkable
      improvement of laboratory medicine.

PMID- 12806920
TI  - [Futue direction of three-year educational establishments for students of medical
      technology].
AB  - The medical laboratory technologist education currently offered at four state run
      junior colleges will be upgraded to higher education as all those junior colleges
      become universities in 2004. It has already been decided that several private
      junior colleges and vocational schools are to be upgraded to universities as
      well. Furthermore, the course will not only be offered in undergraduate
      universities, but also on a postgraduate level, increasing the number of medical
      laboratory technologists with a master's degree or a doctorate. This reform is
      perhaps due to a demand for medical laboratory technologists of higher quality
      because of such social conditions as a highly-sophisticated information society,
      advancement in healthcare and medicine, and transition from volume to quality. It
      is also a measure for securing further capacity by seeking adequate human
      resources because of the declining population in the 18-year-old bracket, due to
      the declining birth rate. In such a condition, the direction three-year
      educational establishments must take is to nurture human resources with qualities
      that compare favorably with university graduates. As ways of accomplishing this,
      we could focus on practical technological education at vocational schools with
      the educational period set at four years, or recruit and train university
      graduates with rudimental abilities, as they do at specialist postgraduate
      schools.

PMID- 12806921
TI  - [Trial and results of the educational curriculum system of the Tokyo Medical and
      Dental University for the Laboratory Scientists].

PMID- 12806922
TI  - [Fundamental curriculum in University Education of Medical Technologists: special
      practice for clinical medicine and biotechnology].
AB  - This is the summary of my talk about the new concept of education for medical
      technologists. In Osaka University, the course for laboratory medicine changed
      from a 3-year to a 4-year training course, and our faculty started a new
      curriculum of special practice in clinical medicine and biotechnology for first
      year undergraduate students from 1997. This special practice in clinical medicine
      consists of three parts, encompassing learning in the essential divisions of the
      hospital, bedside learning, and presentation in case conferences. Students visit
      from time to time to seven divisions, outpatients' clinic, surgical operation
      room, laboratory for radiological examination, rehabilitation rooms, pharmacy,
      central storage room for medical records, and the department of medical
      informatics. The aim of this round practice is to broaden their review of
      clinical medicine. They also go to the bed side of one patient in the ward for 4
      weeks especially for learning about values of laboratory data. They follow up the
      laboratory data and go with the patient to clinical physiological examinations.
      Finally, they present their case to all their teachers and class mates in a semi
      congress style and are evaluated with scores by the staffs.

PMID- 12806923
TI  - [Education of medical technologists in North America].
AB  - The increasing complexity of diseases and advancing medical technologies have
      recently raised the number of test items and their use. This has caused each
      department to ask for clinical support by medical technologists, including
      consultation services on clinical laboratory tests in Japan. Under these
      circumstances, we think it is necessary to consider a Japanese education system
      for medical technologists to foster people with advanced ability capable in
      providing adequate clinical support. It is important that we study medical
      technologist systems and education systems superior to than ours. Therefore, to
      investigate the state of the Japanese education system for medical technologists,
      we conducted a comparison between the medical technologist systems and education
      systems in foreign countries and those of Japan. The social background in which
      medical technologists are positioned, their scope of work, and the education
      systems overseas are different from Japan on many points and we were given many
      suggestions for what a system in Japan should be like.

PMID- 12806924
TI  - [Diagnostic tests approved by Ministry of Health and Welfare (April 2003)].

PMID- 12806925
TI  - [Severe acute respiratory syndrome].

PMID- 12806926
TI  - [Evaluation of a rapid IgM antibody detection kit for diagnosis of Mycoplasma
      pneumoniae infection during childhood].
AB  - We evaluated the utility of a rapid detection kit for Mycoplasma pneumoniae (Mp)
      specific IgM antibody, ImmunoCard (IC) Mycoplasma Test (Meridian Bioscience,
      USA), with regard to mycoplasmal infection during childhood. For this purpose, 30
      serum samples were obtained from 23 pediatric patients with serologically proved
      mycoplasmal pneumonia at and younger than 16 years of age. The diagnosis of
      mycoplasmal infection was made by means of a particle agglutination (PA) method,
      which was on the basis of 1) a four fold or greater rise with paired sera or 2)
      at and more than 1:640 with a single, acute phase serum. In addition to the IC
      test, Mp-specific IgM and IgG antibodies were measured by ELISA tests (Zeus, USA)
      for comparison. A final observation time for colorization in the IC test was
      prolonged to 10 min in this study. The reason for this was because only 8 samples
      which were obtained 5 days or more after the onset of fever (37.5 degrees C) were
      judged to be positive when the observation time was confined to 5 min as the
      manufacturer recommended. A judgment was always made by more than one persons.
      Since we intended to find out the diagnostic capability of the IC test using an
      acute phase single serum, we focused on 18 cases for which samples were obtained
      within 5 days of the onset of fever. As a result, 13 (72%) cases were judged to
      be positive for Mp by the IgM ELISA test, 6 (33%) cases, including 5 cases in
      which the result was interpreted to be positive by a 10-min observation, were
      judged to be positive by the IC test, and 4 (22%) cases were judged to be
      positive by the PA test when titers of at and more than 1:320 by an acute phase
      single serum were interpreted as significant. Through this study we felt that the
      sensitivity of the IC test was not so high as have been previously reported in
      the literatures (the IC test was occasionally positive even in the range of <
      1:40 by a PA test). On the other hand, we believe that the 10-min observation for
      final colorization did not significantly affect the specificity of the IC test as
      long as it was compared with the results by the ELISA IgM test. So far, the
      rapidity in obtaining results, and the simplicity of handling by which the test
      can be performed in an outpatient clinic, are thought to be the major advantages
      of the IC test.

PMID- 12806927
TI  - [Cytotoxic effect of antiseptics: comparison In vitro. In vivo examination of
      strong acidic electrolyzed water, povidone-iodine, chlorhexidine and benzalkonium
      chloride].
AB  - Cytotoxic effect and guinea pig wound cure stage, pus fabrication presence in
      infected wound were compared with strong acidic electrolyzed water (AcEW) and
      povidone-iodine solution (PVP-I), chlorhexidine (CHG) and benzalkonium chloride
      (BAC). It gave the following results: In a cytotoxic test, the toxicity was
      recognized in 0.1%-0.01% PVP-I, in 0.0002-0.0004% CHG, in 10-0.1 micrograms/ml
      BAC, but there was no toxicity in AcEW. By a guinea pig wound cure process, no
      significance was recognized between each pharmaceutical agent in epidermal cell
      migration, but by an inflammation locus area, the significance was considerable
      in comparison with no-treatment. The pyopoiesis of P. aeruginosa infected wound
      was recognized in a ratio of 38.2% physiological saline, 27.3% CHG, 20.6% PVP-I
      and 12.1% AcEW. When pollution locus includes an infection image of bacteria,
      while draining AcEW instead of physiological saline, disinfection, indication was
      expected, and, as for the disorder in cure stage. I do not agree with that
      mentioned above. As for AcEW, availability by organism use was recognized for the
      cytotoxic effect of antiseptic instead of action of acceleration for wound cure.

PMID- 12806928
TI  - [Investigation on zoonoses among veterinary technicians].
AB  - We conducted a survey on how much veterinary clinics staff, mostly veterinary
      technicians, know about zoonosis and how extensively they inform pet owners of
      ways to prevent zoonosis. The number of people who took part in the survey was
      1,057. The ratio of people who said their knowledge on zoonosis is "neither
      sufficient nor insufficient" was 53.8%, which is larger than the ratio of people
      who replied "sufficient" or "insufficient." The percentage of those who said
      their way of giving information on zoonosis to pet owners is "neither sufficient
      nor insufficient" was 52.4%. The ratios of people who knew about Spirometra
      erinacei, Dipylidium canium or Giardia lamblia were 64.7%, 73.6% and 57.6%,
      respectively. The longer they worked, the more they knew about Cryptosporidium
      spp. (20.1%), Hymenolepis nana (31.8%), Echinococcus spp. (45.7%), Ancylostoma
      spp. (73.3%), Dirofilaria immitis (80.5%), Toxoplasma gondii (82.4%), and
      Toxocara canis (86.5%). It seems that systematic continuing education and
      opportunities to acquire new knowledge are not sufficient for those working in
      veterinary clinics, and this needs to be corrected.

PMID- 12806929
TI  - [Report of questionnaire survey for methicillin-resistant Staphylococcus aureus
      and penisillin-resistant Streptococcus pneumoniae between 1998 and 2000 in the
      Kinki district].
AB  - Kinki Infection Working Group made an annual (1998-2000) comparative study of an
      epidemiological investigation for Staphylococcus aureus and Streptococcus
      pneumoniae in the Kinki district. The number of S. aureus and methicillin
      resistant S. aureus (MRSA) isolated decreased for three years, but the isolation
      frequencies of MRSA has not changed which was approximately 60%. All strains of
      MRSA were not resistant to vancomysin (VCM) and teicoplanin (TEIC), and the
      frequencies of resistance to sulfamethoxazole-trimethoprim (ST) and arbekacin
      (ABK) were 0.1 to 0.7% and 1.9 to 3.1%, respectively. On the other hand, the
      number of S. aureus and penicillin-resistant S. pneumoniae (PRSP) isolated did
      not show a consistent tendency, but the isolation frequencies of PRSP has
      increased for three years. All strains of PRSP were sensitive to vancomycin
      (VCM), but the frequencies of resistance to cefaclor and other some antibiotics
      have increased.

PMID- 12806930
TI  - [Purulent meningitis caused by Streptococcus suis in a pig breeder].
AB  - A case of Purulent meningitis caused by Streptococcus suis type 2 is reported
      here. It occurred in a 58-year-old male pig breeder. A few days before
      presentation, the patient had experienced headache, systemic articular pain and
      fever (38.8 degrees C). On admission, he was stuporous and had neck stiffness and
      hemiparesis. Examination of cerebrospinal fluid showed purulent meningitis. The
      cultures identified Streptococcus suis II by PCR and specific serum. 2 months
      later, the patient was discharged in good clinical condition except for hearing
      loss. Streptococcus suis is known to be an important pathogen in the swine
      industry, this report is the first case of S. suis meningitis in man, in Japan.

PMID- 12806931
TI  - [A simple qualitative assay for intracellular growth of Legionella pneumophila
      within Acanthamoeba culbertsoni].

PMID- 12806932
TI  - [A possible case of transmission of cytomegalovirus from a breast-fed infant to
      its father].

PMID- 12806933
TI  - [Chemotherapy-induced emesis and anti-emetic drugs].

PMID- 12806934
TI  - [Importance of treatment for adverse drug reactions in cancer treatment].

PMID- 12806935
TI  - [Adverse effects in cancer chemotherapy].
AB  - The toxicity of cancer treatment affects adversely the QOL of patients and limits
      the intensity of treatment that can be administered. In this article,
      characteristics of these each adverse reactions are described. In the last
      decade, several means have been developed that offer possible prevention and
      reduction from the adverse effects of a range of cancer treatment. Furthermore,
      recently, practice guidelines are systematically developed to assist the
      practitioner and patients decision about appropriate management for specific
      clinical circumstances. However, it is important to realize that these guidelines
      cannot always account for individual variation among patients. 'Close clinical
      monitoring, early recognition of toxicities and toxicity syndromes, aggressive
      therapeutic interventions, and withholding therapy in the presence of severe
      treatment related toxicities' is always required.

PMID- 12806936
TI  - [The onset of adverse events induced by chemotherapy for patients with
      malignancy].
AB  - Chemotherapy is frequently adopted for patients with malignancy, as one of type
      of multidisciplinary treatment. Each chemotherapeutic drug has the potential to
      induce various adverse events in the patients receiving chemotherapy. Before the
      application of chemotherapy, sufficient knowledge for chemotherapeutic drugs and
      careful evaluation for patients are indispensable to avoid severe adverse events,
      since uncontrolled adverse events cause a markedly lower quality of life,
      incompletion of the treatment modality and life-threatening of patients. The
      onset of each adverse event is influenced by the host condition, e.g., sex, age,
      allergic status, complication, nutritional condition, the administration method,
      e.g., dose, route, course, combined agents, and combined therapy, e.g.,
      radiotherapy. Frequent adverse events are discussed in terms of the onset.

PMID- 12806937
TI  - [Adverse reactions of cancer chemotherapy and fluid replacement].
AB  - Clinical oncologists and physicians handling anticancer drugs need to be
      thoroughly aware of anticancer drug adverse reactions, and have all the necessary
      skills to deal with such events if they occur. This chapter discusses anticancer
      drug adverse reactions requiring fluid replacement. Adverse reactions that
      require fluid replacement are in general considered serious. Most are at least
      grade 3 events (serious/high toxicity) based on the NCI-CTC ver 2 classification
      and require immediate treatment. Here we discuss the general view of fluid
      replacement for dehydration caused by gastrointestinal toxicity, fluid
      replacement for nephrotoxicity, hemorrhagic cystitis, tumor lysis syndrome that
      sometimes requires substantial fluid replacement and SIADH that is a condition
      requiring a prudent approach to fluid therapy, including also specific methods of
      fluid replacement.

PMID- 12806938
TI  - [Prevention of side effects in the chemotherapy at home].
AB  - The chemotherapy at home is most different from the conventional chemotherapy
      because of the condition not to watch patients all the time. In order to avoid
      serious side effect it is necessary to administrate some drugs continuously or
      together. It is useful to use portable pump system. It is also important to
      educate patients about the chemotherapy at home and to establish the observation
      system against the trouble from the chemotherapy at home. As the chemotherapy at
      home is safe if we know the side effect well, this type of chemotherapy will
      become the one of main branch in the chemotherapy of colorectal cancer.

PMID- 12806939
TI  - [Common toxicity criteria: version 2.0, an improved reference for grading the
      adverse reaction of cancer treatment].
AB  - In 1998, the National Cancer Institute (NCI) made an effort to revise and expand
      the Common Toxicity Criteria (CTC) in cancer treatment. New CTC version 2.0
      includes more than 279 individual adverse events with more than 24 of these
      applicable to adverse reaction category. The Radiation Therapy Oncology
      Group(RTOG) Acute Radiation Morbidity Scoring Criteria and BMT Complex/Multi
      Component Events were added to New CTC version 2.0. CTC version 2.0 represents an
      improvement in the evaluation and grading of toxicity for all modalities in
      cancer treatment.

PMID- 12806940
TI  - [Nursing measures against adverse reaction from anti-cancer chemotherapy].
AB  - Combination chemotherapy for leukemia develops bone marrow suppression. Infection
      or hemorrhage disorders the treatment, and may influence the clinical result. The
      caring staff must understand the pathology of bone marrow suppression. Visitors
      observe the hospital rules. Foods are also limited, city water and uncooked foods
      are prohibited. To keep oral cavity clean, pretreatment of some decayed teeth,
      and frequent gargling with sterilized water are needed. Defecation control is
      important. Sitz bath or shower toilet is helpful. Hand cleaning is essential for
      before a meal, after defecation and after a going out. Bathing is fundamental to
      cleaning body. No bathing is dirty. Medical catheters are checked up every day.
      Thrombocytopenia(< 30,000/microliter) develops a spontaneous bleeding. Severe
      thrombocytopenia(< 10,000/microliter) does a fatal organ bleeding.

PMID- 12806941
TI  - [Bone marrow suppression].
AB  - Bone marrow suppression is one of the most popular side effects of cancer
      chemotherapy. Bone marrow suppression includes neutropenia, anemia and
      thrombocytopenia. Clinical application of cytokine is useful in the treatment of
      bone marrow suppression due to cancer chemotherapy. Granulocyte colony
      stimulating factor(G-CSF) is useful in the treatment of neutropenia.
      Erythropoietin(EPO) is useful is the treatment of anemia. However, EPO is not
      widely used in Japan yet. Clinical application of varions cytokines will bring
      forth much improvement in the treatment of bone marrow suppression due to cancer
      chemotherapy.

PMID- 12806942
TI  - [Nausea and vomiting].
AB  - Nausea and vomiting are the most distressing side effects reported by patients
      undergoing CDDP-based cancer chemotherapy. Dopamine receptor antagonists and
      corticosteroids are used as anti-emetics for chemotherapy induced nausea and
      vomiting. Recently, a highly selective 5-HT3 receptor antagonist are proved to
      demonstrate antiemetic activity. 5-HT3 receptor antagonists are developed such as
      Granisetron, Ondansetron, Ramosetron, Azasetron. For acute emesis, complete
      control of vomiting was achieved in 80% of patients receiving 5-HT3 receptor
      antagonists. Though, it is reported to be only 20% effective for the complete
      control of delayed emesis. Psychiatric medications sometimes play a prominent
      role in the control of persisting emesis, particularly anticipatory or
      conditioned nausea. Nausea and vomiting are well controlled using various anti
      emetics considering patient's condition and chemotherapy schedule.

PMID- 12806943
TI  - [Mucositis].
AB  - Mucositis is a significant dose-limiting factor associated with cancer
      chemotherapy and radiotherapy. For exact management, an early diagnosis and
      precise evaluation are surely required. A basis of the prevention and care of
      stomatitis is maintaining cleanliness and moisture in the mouth. The medical
      treatment plans of oral mucositis are a measure against infection, and prevention
      against symptoms, and are restoration of a tissue damage, and treatment to sharp
      pain. However, there is no still established prevention method. As for the
      present condition, in the clinical practice, there are many portions depending on
      experiential knowledge. In this paper, it outlined including Empiric therapy
      about measures of oral mucositis.

PMID- 12806944
TI  - [Management of cancer treatment-related diarrhea and constipation].
AB  - Digestive complications are frequent dose-limiting side-effect of chemotherapy.
      Diarrhea and constipation can affect quality of life and alter optimum treatment
      efficacy. The incidence and the severity of these toxicities have to be
      systematically evaluated in order to provide specific curative and preventive
      treatments. This review shows the recommended guidelines for the treatment of
      chemotherapy-induced diarrhea and the recent therapeutic approaches. The
      management of gastrointestinal graft-versus-host disease and neutropenic
      enterocolitis is also described. Prevention and early recognition is critical to
      avoid sever life-threatening complications and improve quality of life.

PMID- 12806945
TI  - [Prevention and management of nephrotoxicity from anti-cancer agents].
AB  - Nephrotoxicity is an inherent adverse effect of certain anticancer drugs.
      Mechanisms of chemotherapy-induced renal dysfunction generally include damage to
      vascular or structures of the kidneys, hemolytic uremic syndrome and prerenal
      perfusion deficits. Patients with cancer are frequently at risk of renal
      impairment secondary to disease-related and iatrogenic causes. This article
      reviews the prevention and management of anticancer drug-induced renal
      dysfunction. Cisplatin and carboplatin cause dose-related renal dysfunction. In
      addition to elevation of serum creatinine levels and uremia, electrolyte
      abnormalities, such as hypomagnesemia and hypokalemia, are well known adverse
      effects of cisplatin. Methotrexate can cause elevation of serum creatinine
      levels, uremia and hematuria. Acute renal failure is reported after high dose
      methotrexate therapy. Urinary alkalization and hydration confer protection
      against methotrexate-induced renal dysfunction. Dose- and age-related proximal
      tubular damage is an adverse effect of ifosfamide. In addition to renal wasting
      of electrolytes, glucose and amino acids, Fanconi syndrome and rickets after
      ifosfamide administration have been reported in the literature. Hemolytic uremia
      is a rare but serious adverse effect of gemcitabine.

PMID- 12806946
TI  - [Hepatotoxicity of chemotherapy].
AB  - Patients who will receive chemotherapy require careful assessment of liver
      function prior to treatment to determine which drugs are not appropriate, and
      which drug need dose modification. Many medications, alcohol has their more or
      less hepatotoxic effect, so because of their immunocompromise state, some body
      are prone to liver infection, including viral hepatitis. Lamivudine is effective
      in treating hepatitis B reactivation during chemotherapy. Now, the increased use
      of high-dose regimens with bone marrow or stem-cell support has been shown the
      drugs toxicities complication more, which does not observed in with conventional
      doses. Clinical judgment and a high index of suspicion remain critical tool in
      preventing and treating hepatic manifestations of cancer chemotherapy.

PMID- 12806947
TI  - [Cardiovascular complications in oncology patients].
AB  - Cancer patients receiving chemotherapy have an increased risk of developing
      cardiovascular complications even if they have normal hearts, and the risk is
      greater if there is known history of heart disease. Various clinical cardiac
      complications that have been reported are arrhythmias, cardiomyopathy, vaso
      occlusion or vasospasm resulting in angina or myocardial infarction. It is well
      know that cardiovascular complications in oncology patients is caused by
      anthracyclines. The trastuzumab as the new treatment option for the metastatic
      breast cancer may be associated with the development of a clinically significant
      cardiotoxicity. We described and reviewed the cardiotoxicity in oncology
      patients.

PMID- 12806949
TI  - [Chemotherapy induced neurotoxicity].
AB  - Lately, the focus of chemotherapy has become not only treating cancer but also
      maintaining patients' quality of life. Drugs used in chemotherapy can cause
      damage and toxicity in normal cells as well as cancer cells. The degree of damage
      could cause dose limiting toxicity and may become one of the reasons of cessation
      of chemotherapy. Neurotoxicity causes numbness of hands and legs which may
      continue to cause patients' suffering for a long time after the treatment. At
      present, the cause of neurotoxicity induced by chemotherapy is not clear, but it
      is urgent to prevent, identify and treat as early as possible. Methods for
      symptom management to relieve such patients' suffering needs to be developed as
      soon as possible.

PMID- 12806948
TI  - [Pulmonary toxisity].
AB  - Pulmonary toxicities, with special reference to interstitial pneumonia, due to
      cancer chemotherapy and/or chest irradiation were reviewed. Two sorts of
      mechanism of development of the interstitial pneumonia are considered; one is
      directly cytotoxic action to pneumocytes and/or pulmonary capillary endothelium
      and the other is an allergic mechanism against anticancer drug or its
      derivatives. The risk factors of cancer therapy induced interstitial pneumonia
      are an aged, poor performance status, and underlying interstitial pulmonary
      diseases. Recently some new serum markers involving KL-6 for interstitial
      pneumonia have been reported and further studies are needed to clarify whether
      these markers are predictive of subsequent pulmonary damage by anti-cancer
      treatments.

PMID- 12806950
TI  - [The skin and alopecia].
AB  - Adverse skin reactions to anti-tumor agents, can be classified either as general
      symptoms or as local symptoms. The former type of symptom can manifest as
      intoxication dermatosis; however, while its occurrence is rare, the symptom that
      requires the closest attention is toxic epidermal necrolysis, the outcome of
      which is death in most patients. The latter type of symptom includes
      extravasation of anti-tumor agents and alopecia. Treatment of extravasation
      induced skin disorders includes prompt and repeated local injections of steroids,
      while treatment of alopecia includes scalp cooling and external therapies.

PMID- 12806951
TI  - [Malignancy-associated hypercalcemia].
AB  - Bisphosphonates (BPs) constitute a major advance in the treatment of malignancy
      associated hypercalcemia(MAH). BPs correct MAH through the mechanisms of
      inhibition of osteoclastic bone resorption. Although BPs are more potent agents
      than calcitonin in the treatment of MAH, anti-hypercalcemic effect of BPs appears
      more slowly than that of calcitonin. Therefore, combination therapy with BP and
      calcitonin is favorable in the treatment of MAH showing hypercalcemic crisis.
      Zoledronate, most potent bisphosphonate, is apparently superior to pamidronate,
      standard bisphosphonate, in the treatment of MAH. BP therapy develops no serious
      adverse effects (i.e. acute renal failure) in clinical practice. However,
      attention should be paid to BP-induced pyrexia and transient pain increase.

PMID- 12806952
TI  - [Disseminated intravascular coagulation].
AB  - Disseminated intravascular coagulation (DIC) is an acquired syndrome
      characterized by systemic formation of microthrombi and fibrin deposition in the
      vasculature. Cancer is one of the leading cause of DIC, which often complicates
      bleeding tendency and organ dysfunction. Even though DIC therapy is expectant, it
      is still important, since the bleeding tendency limits the quality of patients'
      life remarkably. Heparin, low molecular weight heparin, danaparoid, protease
      inhibitors for coagulation factors and antithrombin III are the choices for DIC.
      However, since the selection of the drugs is different depending on the basal
      disease, it is important to understand the pathophysiology of the individual
      situation. In general, protease inhibitors is recommended for 'fibrinolysis
      dominant DIC' like DIC associated with leukemia and terminal stage solid cancer,
      in contrast, danaparoid and antithrombin III are the first choice for
      'coagulation dominant DIC' like sepsis. Supplement of concentrated platelets and
      fresh frozen should be limited for the patients whose primary disease can be
      controlled.

PMID- 12806953
TI  - [Low dose chemotherapy as a means of reducing toxicity].
AB  - At present, chemotherapy can seldom cure advanced gastrointestinal cancer. Low
      dose chemotherapy of regimen might be called palliative chemotherapy, but there
      has also been a growing interest in low dose chemotherapy as a means of reducing
      toxicity and improving responses. Several combinations such as low dose cisplatin
      (CDDP) + protracted infusional 5-fluorouracil(5-FU), leucoborin(IN) + 5-FU,
      weekly taxane and oral chemotherapy(TS-1) produce objective response in 30-50% of
      patients, and who get PR can actually enjoy improved QOL during the remission.
      Therefore, low dose chemotherapy for gastrointestinal cancer will be proposed
      aiming at some objective and/or subjective response with minimum toxicity to be
      alive as lons as possible.

PMID- 12806954
TI  - [Reduction of adverse reactions of anticancer agents with altered dose and
      schedule].
AB  - It is difficult to find out optimal dose and schedule of anticancer agents. To
      reduce side effects of anticancer agents, there are several methods used: dose
      reduction, analogue development, utilizations of G-CSF or non-anticancer agent
      such as mesna for ifosfamide. Taxane agents such as paclitaxel and docetaxel, are
      widely used for the treatment of cancers of ovary, breast, lung, stomach, and
      head and neck. Dose-limiting toxicity of taxane is Grade 4 leucopenia with usual
      24, 6, and 3-hour infusions. Efforts to reduce this toxicity were made, and one
      hour weekly taxane infusion was found as safe and effective treatment, which is
      now widely used as single agent treatment or in combination. Development of
      paclitaxel one-hour weekly infusion was reviewed, as one example of reducing
      adverse reaction of leucopenia in this article.

PMID- 12806955
TI  - [Management of adverse reactions caused by cancer chemotherapy in elderly
      patients].
AB  - With the prolongation of life expectancy in Japan, cancer is increasing in the
      elderly. Several retrospective studies have shown that the frequency of toxicity,
      response to chemotherapy and overall survival are similar in elderly and younger
      patients with cancer with good performance status. However, because many
      investigators have arbitrarily excluded elderly patients from clinical trials and
      there have been a few clinical trials for elderly patients with cancer, no
      standard treatment in the elderly has been established for most cancer. New
      therapeutic strategies are clearly needed to prolong survival, and to improve
      quality of life in elderly patients with cancer.

PMID- 12806956
TI  - [Economic analysis of adverse events in cancer treatment].
AB  - Faced with limited resources and the desire to improve the quality of cancer
      care, there is an increasing interest among physicians in maximizing gains in
      cancer treatment. This paper discusses where to find cost-benefit estimates for a
      host of adverse events in cancer treatments. In order to clarify the relationship
      between the input resources and economic effects of supportive therapies against
      adverse events, we developed a system model, similar to the Marcov model, of
      prognosis of principal seven cancers and analyzed the balance of patient labor
      productivity (Benefit) and accumulated cancer care costs (Cost). Economic
      analysis is a useful guide to resource allocation and appropriate decision making
      for improving patient's QOL.

PMID- 12806957
TI  - [Palliative care complementing cancer treatment].
AB  - Palliative medicine had conventionally been initiated after all avenues of
      anticancer treatment were exhausted, and the treatment of other medical problems
      was considered inappropriate. However, it is increasingly being recognized that
      the palliative principles and interdisciplinary palliative care should be
      initiated when a patient becomes symptomatic with an incurable disease, and
      should never be withheld only after all modalities of anticancer treatment have
      failed. Palliative care should be regarded as being complementary to direct
      cancer treatment. It should be implemented long before the terminal phases of the
      disease, and integrated in a seamless manner with other aspects of support.
      Palliative care is no longer merely terminal care.

PMID- 12806958
TI  - [Second cancers associated with the cancer treatment and their possible control].
AB  - Second cancers induced by both alkylating agents and topoisomerase II inhibitors
      are reviewed with special reference to their distinct clinical features,
      incidences observed in the population at risk, cumulative risks, underlying
      molecular-genetic abnormalities, and also some detoxifying enzyme polymorphisms
      recently identified. Finally, it was discussed whether we can control these
      devastating diseases in the future.

PMID- 12806959
TI  - [Hematopoietic stem cell transplant in cancer treatment].
AB  - Hematopoietic stem cell transplantation (HSCT) includes bone marrow, peripheral
      blood, cord blood, autologous, allogeneic, related or unrelated. These
      transplants have two main roles in cancer treatment, i.e., supportive treatment
      for marrow toxicity and immunotherapy for cancer cells. HSCT has also severe
      adverse reaction such as, bacterial fungal or viral infection by neutropenia, or
      graft versus host disease by the replacement of immune system. In autologous HSCT
      the main role is to prevent severe marrow toxicity which enables extreme high
      dose of anticancer drug administration. In allogeneic HSCT the main roles become
      both, support for marrow toxicity and immunotherapy, which possibly complicated
      with immunological adverse reactions. In mini-transplant or allogeneic transplant
      with reduced intensity, the main role is immunotherapy. These three kinds of
      transplants have each own indication and conducted in 17,472 patients till 2001
      in Japan.

PMID- 12806960
TI  - [Heart transplantation in Japan].
AB  - Since February 1999, organ transplantation from a brain-dead donor has been
      started in Japan. For more than 3 years, 91 patients underwent organ
      transplantation from 22 donors. Until November 2002, 132 patients have been
      registered to Japan Organ Transplant Network as a heart transplant candidate and
      16 and 9 underwent heart transplantation (HTx) in Japan and abroad, respectively,
      while 37 died during waiting. 11 of 16 HTx recipients were implanted with left
      ventricular assist device (LVAS: Novacor in 2, TCI-IP in 2 and NCVC in 7). all 16
      HTx recipients survived until now. 4 had several rejection episodes which were
      treated successfully. 5 had infection episodes (pneumonia in 3 and CMV infection
      in 2). 13 were already discharged and 9 returned to work.

PMID- 12806961
TI  - [Molecular biological approaches for environmental medicine].
AB  - A revolution in biology and medicine is taking place as a direct consequence of
      rapid developments in the field of molecular biology. The tremendous advances in
      our knowledge of basic molecular genetics and cell biology have opened the door
      for new methods of diagnosis, assessment of individual susceptibility to disease,
      and elucidation of the pathogenesis of disease. These advances will have a
      profound impact on the practice of occupational and environmental medicine. In
      this review, we intend to summarize the approaches we have applied in order to
      deal with the environmental problems we have faced.

PMID- 12806962
TI  - [Molecular biology of iron in nutritional science].
AB  - Iron is regarded as one of the most important nutriments, and many diseases are
      related to iron deficiency or its overload. Approximately 70% of iron in the body
      is located in heme, functioning as hemoglobin, myoglobin, and cytochrome P450.
      Iron itself also has many catalytic functions through the iron-sulfa cluster. It
      is believed that iron and/or heme plays significant roles in regulation of genes,
      however, little about the mechanism has been elucidated. Recently, not only iron
      but also heme has been identified as important regulators of gene activation via
      oxygen sensing. For example, iron controls the oxygen response of HIF-1 activity
      by two mechanisms; in cytosol, the half life of HIF-1 alpha is determined by
      hydroxylation of Pro, and transcriptional activity of HIF1 alpha in nuclei is
      disturbed by hydroxylation of Asn. Hemoproteins in prokaryotes such as FixL, Dos,
      and HemAT were found to be oxygen sensors, however, little has been reported in
      eukaryotes. Our finding on Bach1 seems to be the first report of heme and oxygen
      mediated regulation of genes in vertebrates. Understanding of these newly
      identified mechanisms in iron- and heme-controlled genes is essential in the
      field of nutritional science. We therefore summarize here the recent findings
      indicating mechanisms of iron as transcriptional regulators.

PMID- 12806963
TI  - [Gene-environmental interactions in alcohol-related health problems-
      contributions of molecular biology to behavior modifications].
AB  - High alcohol sensitivity among Asians is mainly due to a genetic polymorphism in
      the low Km aldehyde dehydrogenase (ALDH2) gene. Strong correlations between the
      ALDH2 genotype and alcohol sensitivity or alcohol drinking habits have been
      reported. Another prevalent polymorphism in the alcohol dehydrogenase beta
      subunit (ADH2 gene) among Asians appears to modify skin flushing reactions after
      exposure to ethanol but does not influence alcohol drinking behavior. Both the
      ADH2 and ALDH2 genotypes have been significantly correlated with the risk of
      alcoholism. In a Japanese occupational population, a gene-environment interaction
      of the ALDH2 genotype and daily hassles scores for development of problem
      drinking behavior was observed. Habitual drinkers with the ALDH2*1/*2 genotype
      had higher frequencies of sister-chromatid exchange in cultured lymphocytes and
      higher 8-OHdG levels in polymorphonuclear leukocytes than those with the
      ALDH2*1/*1 genotype. Alcoholics and heavy drinkers with the ALDH2*1/*2 genotype
      have been shown to have significantly elevated risks for esophageal and multiple
      cancers in upper digestive organs than those with the ALDH2*1/*1 genotype. In
      Japan, bronchial asthma patients with the ALDH2*1/*2 genotype have been shown to
      have a significantly elevated risk for experiencing alcohol-induced asthma
      compared with the ALDH2*1/*1 genotype. Providing services to determine these
      genotypes would be of great help for each individual to make a plan for tailor
      made health promotion.

PMID- 12806964
TI  - [Establishment of evidence based health care for common diseases based on genetic
      epidemiological approach].
AB  - With the end of the Human Genome Project, we can foresee on the horizon the
      molecular dissection of common diseases, although we could not have imagined such
      a possibility even 10 years before. As byproducts of the human genome project,
      molecular dissection enables us to provide evidence-based health care against
      common diseases: therapies will become more specific and effective than before
      against individual health risks associated with genetic diversities. In the
      present paper, I will briefly sketch state-of-the-art genetic linkage analysis
      for common diseases and discuss inherent difficulties which hamper our approach.
      Emphasis should be put on some advantages of our country for genetic studies,
      where our local communities still preserves old genetic backgrounds. Such a
      unique feature will facilitate genetic dissections of not only rare hereditary
      diseases but also common diseases, paving the way for genetic epidemiology in the
      next 10 years.

PMID- 12806965
TI  - [Gene-regulating chemoprevention against cancer--as a model for "molecular
      targeting prevention" of cancer].
AB  - Recent progress in molecular biology and genetics has improved understanding of
      the mechanisms of carcinogenesis. However, there are few effective methods for
      prevention or therapies against cancer based on such elucidated molecular
      mechanisms of carcinogenesis. We therefore tried to develop novel methods of
      cancer prevention and therapy based on them. For example, the tumor-suppressor
      gene p53 is mutated in about 50% of human malignancies or in a cancer-prone
      family with Li-Fraumeni syndrome. It is known that p53 stimulates the promoter
      activities of p21/WAF1, gadd45 and bax genes to enhance their expression as a
      transcriptional factor, resulting in cell cycle arrest, DNA repair and apoptosis,
      respectively. Therefore, chemical compounds or food factors that can stimulate
      these genes might compensate for part of the p53 function. As a model of our
      hypothesis, we found that histone deacetylase inhibitors such as butyrate and
      trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Sp1
      sites, resulting in cell cycle arrest. We therefore hypothesized that a strategy
      for up-regulating p53-target genes such as p21/WAF1, gadd45 and bax might be
      useful for cancer prevention or therapy, and termed this method "Gene-regulating
      chemoprevention" or "Gene-regulating chemotherapy" against cancer. In fact,
      butyrate, a short chain fatty acid, exists in colon lumen as a metabolite of
      dietary fiber, and is believed to be preventive against colon cancer. In
      conclusion, we proposed that "Gene-regulating chemoprevention" and "Gene
      regulating chemotherapy" may be new promising strategies for cancer prevention or
      therapy, and histone deacetylase inhibitors are good candidates for these
      strategies. "Gene-regulating chemoprevention" is a particularly suitable model
      for "Molecular-targeting prevention", which we have proposed recently. We believe
      that "Molecular-targeting prevention" will become one of the most important
      concepts in the 21st century for general prevention of a variety of common
      hereditary or non-hereditary common diseases.

PMID- 12806966
TI  - [Reduction in n-3 PUFA levels and EPA/AA ratio in serum after desert travels in
      China].
AB  - OBJECTIVES: The effects of 3 months of desert travel in China on serum fatty
      acids and tocopherol were studied. METHODS: In project staff members (6 males, 3
      females, aged 19-27 years), serum levels of fatty acids and alpha-tocopherol were
      analyzed before and after travel by gas liquid chromatography and high
      performance liquid chromatography, respectively. RESULTS: Comparison of the
      levels before and after the trip showed no differences in serum total
      cholesterol, triglycerides, total protein or alpha-tocopherol. There were no
      changes in the levels of total fatty acids, while the percentage of
      polyunsaturated fatty acids increased (p < 0.05). Levels of n-3 PUFA lowered from
      166 micrograms/ml to 103 micrograms/ml, and those of n-6 PUFA had increased from
      988 micrograms/ml to 1140 micrograms/ml after the trip (p < 0.01 and p < 0.001,
      respectively). No change was observed in the serum levels of alpha-linolenic acid
      (C18:3n-3), but lowering of the levels of eicosapentaenoic acid (EPA, C20:5n-3)
      from 41.4 micrograms/ml to 16.3 micrograms/ml and docosahexaenoic acid (DHA,
      C22:6n-3) from 107.8 micrograms/ml to 71.7 micrograms/ml was found after the trip
      (p < 0.05 and p < 0.01, respectively). Serum levels of linoleic acid (LA, C18:2n
      6) increased from 832 micrograms/ml to 598 micrograms/ml (p < 0.001), and
      arachidonic acid (AA, C20:4n-6) tended to increase. The ratios of n-3/n-6 PUFA
      and EPA/AA decreased from 0.171 to 0.091 and from 0.258 to 0.096 after the trip,
      respectively (p < 0.01 for both). CONCLUSIONS: Our findings indicated that 3
      months of desert travel increased the serum levels of n-6 PUFA and LA and reduced
      the serum levels of n-3 PUFA and EPA and the ratios of n-3/n-6 PUFA and EPA/AA,
      possibly due to a relative essential fatty acid deficiency.

PMID- 12806967
TI  - [Effects of dietary fiber on the glucose tolerance in spontaneously diabetic rats
      -comparison among barley, rice, and corn starch].
AB  - OBJECTIVES: In this study, the effects of a barley diet containing high dietary
      fiber on the onset and development of diabetes mellitus in spontaneously diabetic
      rats was investigated by comparing with a rice diet containing low dietary fiber
      and an alpha-corn starch diet containing very low dietary fiber. METHODS: 30 male
      Goto-Kakizaki (GK) strain rats (8 weeks of age) were randomly assigned to 3
      groups; high barley (HB) group on a barley diet (dietary fiber intake, 1.79
      g/day/rat), rice (R) group on a rice diet (dietary fiber intake, 0.46 g/day/rat),
      and alpha-corn starch (CS) group on an alpha-corn starch diet (dietary fiber
      intake, 0.24 g/day/rat). The carbohydrate (70%), fat (10%), and protein (20%)
      contents of these 3 diets were equal, and the rats were pair-fed each diet for 3
      months. RESULTS: Feeding for 3 months showed that fasting plasma glucose level in
      the HB group was significantly lower than in the R and CS groups; the glucose
      tolerance in the HB group was markedly improved. Moreover, the plasma cholesterol
      and triglyceride levels in the HB group were significantly lower than those of
      the R and CS groups. CONCLUSIONS: Our findings demonstrated that barley enabled
      glycemic control and improved glucose tolerance compared with rice or alpha-corn
      starch.

PMID- 12806968
TI  - [Red blood cell deformability in relation to gender, age, blood pressure,
      obesity, serum lipids, alcohol consumption and smoking].
AB  - OBJECTIVES: To determine the effects of environmental factors on abnormalities in
      red blood cell deformability (RBCD), which may play an important role in the
      development of cardiovascular diseases, a cross-sectional epidemiological study
      was conducted in healthy subjects. METHOD: The subjects were 350 males (mean age
      52.7 +/- 10.3 SD) and 364 females (52.6 +/- 10.4) who participated in a health
      check program in the town of Akabane, Japan, in 1995-1998. Blood and serum were
      obtained to determine the values of RBCD and TP, TG, TCHOL, and HDLC. The inverse
      of RBCD (RBCDI, ms-1) was used as an indicator of RBCD. The subjects were also
      investigated for drinking and smoking habits, BMI, and SBP. Males and females
      were stratified into tertiles for each variable except drinking and smoking. For
      those exceptions, male subjects were stratified into three groups according to
      alcohol consumption (non-drinkers, moderate drinkers (up to 27 ml pure ethanol
      per day), and habitual drinkers (28 ml or more per day)) and according to tobacco
      use (non-smokers, mild smokers (equal or fewer than 20 cigarettes per day), and
      heavy smokers, (more than 20)). Each stratum was further divided into two groups
      according to age (younger, < 50 years; older, > or = 50 years). RESULTS: The mean
      value of RBCDI was significantly higher in males (1.041 +/- 0.135 SD) than in
      females (1.013 +/- 0.113). RBCDI declined with age in both genders. In analyses
      of variance, the averages of RBCDI decreased as TP increased in all ages and in
      both genders and as TCHOL increased in older males. With regard to alcohol
      consumption, the averages of RBCDI were the highest in moderate drinkers in
      younger males. Multiple linear regression analyses showed negative correlations
      between RBCDI values and age, TP or TCHOL values, and showed positive
      correlations between RBCDI values and BMI in males as well as negative
      correlations between RBCDI values and age and TP in females. When alcohol
      drinking was entered into the model, the statistical significance between TCHOL
      and RBCDI disappeared in males. No apparent relations between smoking habit and
      levels of SBP and TG to RBCDI were found. CONCLUSIONS: RBCDI was higher in males
      than in females and higher in the younger group than in the older group. This
      study suggested that TCHOL may lower RBCDI and moderate drinking may improve it.
      Further epidemiological study is required to clarify these relationships.

PMID- 12806969
TI  - [Report on 1st Korea-Japan nephrology forum].

PMID- 12806970
TI  - [A report on the 9th Asian Pacific Congress of Nephrology in Pattaya, Thailand].

PMID- 12806971
TI  - [Asian Pacific Congress of Nephrology 2003].

PMID- 12806972
TI  - [Influence of a long-term load of dietary cholesterol on the rat kidney].
AB  - The involvement of hyperlipidemia in aggravation of nephrosis has remained
      controversial. In this study, to examine the influence of cholesterol on the
      kidney, normal SD rats were loaded with a normal diet(4.4% fat, 0.09%
      cholesterol) plus 0.25% cholesterol for 10 months, and the urinary excretion of
      protein, blood cholesterol level and histological renal changes were compared
      with those in the control group given the normal diet alone. The urinary protein
      excretion was increased after 4 months of cholesterol loading and was about 6
      times the control value at the end of the study(10 months). At 10 months, the
      blood levels of total, HDL- and LDL + VLDL-cholesterols were also increased, and
      the arteriosclerosis index(HDL/LDL + VLDL ratio) was about 1.3 times the control
      value. Histologically, segmental lesions of glomeruli containing sclerosis/PAS
      positive material were stronger than in the control animals. Thus, this study
      revealed increased blood cholesterol and urinary protein excretion and aggravated
      histological changes of the kidney in rats given a long-term cholesterol load,
      suggesting that cholesterol may be a risk factor affecting the kidney.

PMID- 12806974
TI  - [Analysis of factors affecting the course of renal disease progression in
      patients with established renal insufficiency].
AB  - All renal diseases ultimately progress to end-stage renal disease after renal
      dysfunction develops except for acute renal failure or rapidly progressive
      glomerulonephritis. However, renal function can be preserved for long periods in
      patients with mild renal insufficiency. We examined the factors affecting the
      progression of renal disease in patients with established renal insufficiency. We
      enrolled 38 patients with renal insufficiency diagnosed at the first visit and
      who were followed up for at least 3 years. We retrospectively recorded all
      information relating to serum creatinine and blood pressure levels during the
      follow-up periods. The patients were categorized as group A(n = 11), long-term
      renal survivors(at least 8 years), group B(n = 22), short-term renal survivors(3
      to 8 years) and others(n = 5). Basal renal diseases were variable, and included
      IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis,
      hypertensive glomerulosclerosis, tubulo-interstitial disease and lupus nephritis.
      Except for the degree of urinary occult blood, no other clinical data obtained at
      the first visit differed between groups A and B. Overall blood pressure levels
      throughout the entire clinical course also did not differ between the two groups.
      However, mean blood pressure levels before serum creatinine had reached the level
      of 2.0 mg/dl were significantly lower in group A compared with group B (96 +/-
      7.8 vs. 103 +/- 6.3 mmHg, p < 0.05). We considered that the serum creatinine
      level of the so-called "point of no return" might be 2.0 mg/dl. In conclusion,
      blood pressure should be strictly controlled before serum creatinine levels reach
      2.0 mg/dl.

PMID- 12806973
TI  - [Renoprotective effect of triple therapy with low-dose angiotensin receptor
      blocker, low-dose diuretic and Ca-antagonist in hypertensive type 2 diabetic
      patients with overt nephropathy].
AB  - Combination therapy with angiotensin receptor antagonist(ARB) plus angiotensin
      converting enzyme inhibitor(ACE-I) (ARB/ACE-I) was efficacious in reducing
      proteinuria in patients with progressive renal disease. However, this therapy may
      be associated with the worsening of anemia and hyperkalemia. The present study
      addressed whether or not triple therapy with low-dose ARB, low-dose diuretic (D)
      and calcium channel blocker(CCB) (ARB/D/CCB) is as effective as therapy with low
      dose ARB/ACE-I in retarding the progression of overt diabetic nephropathy. In the
      triple therapy, the patients were initially subjected to monotherapy with CCB for
      24 weeks. Low-dose ARB and low-dose D were added to the treatment for an
      additional 24-week period. In parallel, patients undergoing double therapy were
      initially treated with low-dose ACE-I alone for 24 weeks, and then low-dose ARB
      was added for an additional 24-week period. The results were as follows: 1) In
      the triple therapy, blood pressure was reduced by 9 mmHg in systole and 5 mmHg in
      diastole (not significant) compared to monotherapy with CCB. There was a
      significant decline in proteinuria (3.3 +/- 1.2 g/day in the CCB-treated period
      vs. 2.1 +/- 1.0 g/day in the ARB/D/CCB-treated period, n = 12, p = 0.0143).
      Furthermore, a significant improvement in the slope of reciprocal serum
      creatinine concentration(1/Cr) was found in response to triple therapy(1/Cr: 
      0.0118 +/- 0.0009 in the CCB-treated vs. -0.0035 +/- 0.0028(I/mg/dl/month) in the
      ARB/D/CCB-treated period, n = 12, p < 0.001). There was neither a worsening of
      anemia nor an increase in the serum potassium(K) concentration. 2) In the double
      therapy, blood pressure was reduced by 12 mmHg in systole(p = 0.0079, n = 11) and
      6 mmHg in diastole(n = 11, p = 0.0037) compared to the monotherapy with ACE-I. A
      significant improvement in the slope of 1/Cr was found in the double
      therapy(1/Cr: -0.0095 +/- 0.0052 in the ACE-I treated period vs. -0.0029 +/-
      0.0028(I/mg/dl/month) in the ARB/ACE-I, n = 11, p < 0.001). In addition, there
      was a substantial reduction in hematocrit and increase in serum K concentration.
      The present result suggests that triple therapy consisting of ARB/D/CCB is as
      efficacious as double therapy with ARB/ACE-I in protecting the kidney from the
      progression in patients with diabetic overt nephropathy. The former may be
      expected to have less adverse effects.

PMID- 12806975
TI  - [Peritoneal dialysis catheter-related complications].
AB  - The introduction of a double-cuff swan neck type catheter has reduced the
      frequency of peritonitis. The frequency of complications associated with
      insertion of this catheter has remained unknown. We evaluated these complications
      in patients aged < 20 years at the start of the chronic peritoneal dialysis using
      double-cuff swan neck catheters. SUBJECTS AND METHODS: The data from 221 double
      cuff swan neck catheters of 126 patients inserted in our hospital between 1990
      and 2001 were compared with 102 single-cuff straight catheters of 54 patients
      between 1982 and 1990. The frequency of catheter-related complications, such as
      dislocation, leakage with in/outflow malfunction and infection(exit-site/tunnel
      infection and peritonitis within a month after catheter insertion) were
      estimated. RESULTS: We observed 37 dislocations(17%), 37 leakages(17%) and 36
      infections(16%) of all double-cuff swan neck catheters. Twenty-nine catheters
      were removed due to catheter-related complications: 18 dislocations(8%), 2
      leakages(1%) and 9 infections(4%). Catheter removal due to dislocation occurred
      significantly more frequently in 12% of children who were > or = 6 years old than
      in 1% of children < 6 years old(p = 0.002). Eighty-three percent of dislocations
      could be returned by the whiplash method(alpha-replacer, JMS, Tokyo). Of all
      single-cuff straight catheters, 10 catheters were removed due to catheter-related
      complications: 4 dislocations(4%), 6 leakages(6%) and 12 infections(12%).
      CONCLUSION: A single-cuff straight type catheter was more frequently replaced
      because of leakage and infection than a double-cuff swan neck type catheter. A
      double-cuff swan neck catheter was more frequently replaced because of
      dislocation than a single-cuff straight catheter. When a double-cuff swan neck
      catheter is inserted particularly in older children, care should be taken to
      avoid dislocation.

PMID- 12806976
TI  - [A case of sarcoidosis overlapping with rheumatoid arthritis].
AB  - We report the case of a 54-year-old woman who presented on May 28, 2001 with
      sarcoidosis overlapping with rheumatoid arthritis. She had experienced morning
      stiffness 2 years previously and was diagnosed as having rheumatoid arthritis.
      She had been treated with bucillamine and loxoprofen for 3 months. In October
      2000, she developed proteinurea. The patient discontinued treatment with
      bucillamine and loxoprofen. Proteinurea persisted, and the patient's renal
      function declined. On admission, subcutaneous nodules were palpable in the
      patient's legs. The patient's serum creatinine and calcium levels were 2.49 mg/dl
      and 11.6 mg/dl, respectively. Intact-PTH was suppressed, and PTHrP was not
      elevated. Despite the presence of hypercalcemia, the patient's serum 1 alpha
      25(OH)2D3 was not suppressed. Serum ACE and lysozyme levels were elevated beyond
      the normal ranges. A renal biopsy was performed, and non-caseous epithelioid
      granuloma was found in the renal interstitium. Based on the histological
      findings, the patient was diagnosed as having sarcoidosis. Following treatment
      with prednisolone, the patient's serum calcium levels returned to normal and her
      renal function improved.

PMID- 12806977
TI  - [Henoch-Schonlein purpura nephritis in a patient infected with the human
      immunodeficiency virus].
AB  - There are various forms of renal lesions in patients with human immunodeficiency
      virus(HIV), however reported cases of immune-complex glomerulonephritis are
      scarce. Here we describe an HIV-positive patient with Henoch-Schonlein purpura
      nephritis(HSPN), which presented as nephrotic syndrome. In addition to therapy
      combined with glucocorticosteroid and inhibition of the renin-angiotesin
      system(RAS), plasmapheresis and antiretroviral therapy produced a favorable
      outcome. A 26-year-old HIV positive man was admitted for purpura on both lower
      limbs. Despite glucocorticosteroid treatment, purpura recurred and urinary
      protein increased to 5-10 g daily. HSPN was diagnosed based on the skin and renal
      biopsies. During 2 months of treatment with combined glucocorticosteroid and RAS
      inhibition, nephrotic syndrome persisted. He received double filtration
      plasmapheresis(DFPP). Soon after, urine protein decreased to 2-3 g daily and
      macrohematuria decreased. The second renal biopsy showed a decrease in IgA
      deposition and improvement of acute inflammatory changes. In addition, highly
      active antiretroviral therapy was started to reduce the high viral load. After 3
      weeks, HIV-1-RNA rapidly decreased and urine protein decreased to 1 g daily.
      After a year, urinary protein was negative, but mild microhematuria persisted. We
      speculate that the refractory nephrotic syndrome in this patient might be
      associated with the abnormal immunological condition due to HIV infection.

PMID- 12806978
TI  - [Acute encephalopathy due to thiamine deficiency with hyperammonemia in a chronic
      hemodialysis patient: a case report].
AB  - Hemodialysis(HD) patients are at risk for thiamine deficiency because of low
      intake and accelerated loss of thiamine during HD. We report here an HD patient,
      an 82-year-old woman, who developed acute encephalopathy due to thiamine
      deficiency with hyperammonemia. She was admitted to Nishikawa Town Hospital due
      to pneumonia and was treated with ABPC/SBT for one week. While she was cured of
      pneumonia, she had a persistently poor appetite. On the twenty-fourth day after
      admission, HD with intradialytic parenteral nutrition(IDPN), which consisted of
      10% glucose 500 ml, in order to correct her malnutrition, was started. She
      suddenly presented confusion, speech disturbance and ophthalmoplegia. HD with
      IDPN was stopped after two hours because of her symptoms. Laboratory studies
      disclosed plasma glucose of 186 mg/dl and serum ammonium of 155 micrograms/dl.
      Arterial blood gas analysis(inhaling 3 l/min O2) showed severe metabolic acidosis
      and respiratory acidosis (pH 7.138, pCO2 44.8 mmHg, pO2 108.9 mmHg, HCO3- 15.1
      mmol/l). Her malnutrition, unexplained metabolic acidosis and neurological
      presentation raised the suspicion of acute encephalopathy due to thiamine
      deficiency. Fursultiamine 100 mg was administered intravenously. After two hours,
      metabolic acidosis disappeared (pH 7.437, pCO2 33.9 mmHg, pO2 161.0 mmHg, HCO3-
      22.9 mmol/l), and she regained her clear consciousness and serum ammonium
      decreased at 16 micrograms/dl on the next morning. Serum lactate and thiamine
      level were shown later to be 57.5 mg/dl and 27 nmol/l, respectively. Her clinical
      course suggests that the glucose load including IDPN may have caused
      deterioration of the neurological disorder under the condition of thiamine
      deficiency. Furthermore, it is possible that a relationship exists between
      thiamine deficiency and hyperammonemia.

PMID- 12806979
TI  - [Two cases of interstitial nephritis with primary Sjogren's syndrome successfully
      treated by steroid therapy].
AB  - We have experienced two cases of interstitial nephritis with Sjogren's syndrome
      successfully treated by steroid therapy. Case 1. A 50-year-old woman was admitted
      because of rash and arthralgia of the limb. Although her renal function was
      normal, serum IgG was extremely high and gallium-67 scintigrams indicated
      abnormal uptake in both kidneys with swelling on CT scans. Renal biopsy specimens
      showed a patchy dense interstitial infiltration of lymphocytes, monocytes and
      partly plasma cells with tubular cell atrophy. To suppress an excessive immune
      reaction, oral prednisolone was administrated at a dose of 30 mg/day. Six weeks
      after inception of the therapy, re-biopsy specimens showed a decrease in
      interstitial infiltration, particularly plasma cells, and interstitial fibrosis
      did not progress. After 8 weeks, the serum IgG level was normalized. Case 2. A 57
      year-old woman was found to have renal involvement(serum creatinine level: 2.2
      mg/dl) and anemia. Clinical findings suggested primary Sjogren's syndrome with
      renal tubular acidosis. Renal biopsy specimens showed a moderate to severe
      interstitial infiltration of inflammatory cells. After inception of steroid
      therapy(prednisolone 40 mg/day), renal involvement and renal anemia gradually
      improved. The renal function has been kept stable(serum creatinine level: 1.5
      mg/dl) for 9 years by low-dose steroid therapy. These two cases suggest that
      steroid therapy plays two important roles: controlling of the acute immune
      reaction that causes renal fibrosis to progress in case 1, and long-term
      preservation of the renal function by the continuous use of low-doses in case 2.

PMID- 12806980
TI  - [Clinical analysis of pulmonary tuberculosis found by mass screening medical
      examination].
AB  - Five hundred twenty-one patients with pulmonary tuberculosis were diagnosed in
      our three affiliated hospitals during past 10 years. Among them, 43 cases (22 men
      and 21 women; mean age 54.8 years) who were detected by active case-finding were
      clinically evaluated. Most of them were detected in an annual mass screening
      examination, but seven cases were found by contacts examination which was
      performed on subjects who were contacted with newly diagnosed patients with
      pulmonary tuberculosis. Fifteen of them were socially jobless on admission.
      Eighteen cases (41.9%) had underlying diseases, and gastrointestinal diseases and
      diabetes mellitus were most frequently observed. The final diagnosis was
      confirmed through bronchoscopic specimens in 18 cases in which Mycobacterium
      tuberculosis could not be detected from the sputum. Regarding radiological
      findings according to the criteria of the Japanese Society of Tuberculosis, most
      cases had unilateral distribution, and were classified as type III (active, non
      cavitary) for characteristics and 1 (minimal) for the extent of lesions.
      Treatment using combination therapy with four drugs including pyrazinamide was
      performed for over half of these cases and subsequently the clinical efficacy was
      good except in one case who died due to worsening of the underlying disease. Anti
      tuberculous drugs were generally administered to cases suspected of having
      pulmonary tuberculosis on chest X-ray. However, early diagnosis using
      bronchoscopy and early treatment seems to be useful, when Mycobacterium
      tuberculosis is not detected in the sputum.

PMID- 12806981
TI  - [Evaluation of the Mycobacteria Growth Indicator Tube system for detection and
      quantification of mycobacteria from clinical specimens].
AB  - The Mycobacteria Growth Indicator Tube (MGIT) system, a broth system for
      detection of mycobacterial growth, has been shown to be more sensitive and rapid
      compared with the egg-based Ogawa solid media, while the lack of ability to
      quantitate bacterial growth is the problem. We compared mycobacterial growth in
      the MGIT and the Ogawa systems, and evaluated the relationship between detection
      time in the MGIT system and bacterial CFU on Ogawa egg medium. A total of 413
      respiratory specimens from 245 patients were included in the study, of which
      Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. kansasii were
      recovered from 127, 42 and 6 specimens, respectively. Recovery rates were
      significantly higher and detection time was significantly shorter in the MGIT
      than in the Ogawa for MTB and MAC. Detection time in the MGIT was significantly
      shorter in smear positive specimens than in smear negative ones for MTB and MAC.
      There was a significant negative correlation between CFUs on Ogawa egg medium and
      detection time in the MGIT system for the MTB, therefore, this system may have an
      ability to quantitate live mycobacteria according to the detection time.

PMID- 12806982
TI  - [A suspected case of mass outbreak of tuberculosis infection in a small company
      separated into two floors].
AB  - The number of tuberculosis outbreak among adult groups has increased. In some of
      them, it is difficult to identify the route of infection and sometimes many
      people are involved in the outbreak. We experienced a suspected case of mass
      outbreak in a small company separated into 2 floors. The first patient, who lived
      in another city, was diagnosed as pulmonary tuberculosis in April with bilateral
      extensive cavitary lesions complicated with pleurisy on chest X-ray, and his
      sputum smear was Gaffky No. 8 and culture (+) (resistant to isoniazid). We
      conducted tuberculin skin test (TST) for those under-30 year-old. In TST, 4
      persons showed strong positive reaction. After consulting with tuberculosis
      specialists, three were diagnosed as newly infected with tuberculosis and one as
      hilar lymph node tuberculosis. So we added 25 staffs under 60s for TST and found
      that another 13 people were suspected to be infected with tuberculosis. From the
      initial information, the index cast was said to work only in the 2nd floor, so
      the staffs in 7th floor were excluded from the survey. Through the interview with
      staffs by a public health nurse and an inspection of the work place with sanitary
      inspectors, it was concluded to expand the survey to the staffs working in the
      7th floor, and another newly infected persons were found. Staffs in a small
      company do not belong to "danger group", but the importance of investigations by
      public health officials was suggested in the case of suspected outbreak.

PMID- 12806983
TI  - [A case of isoniazid sodium methanesulfonate induced interstitial pneumonia].
AB  - A 71-year-old male was admitted to our hospital with dyspnea on effort. He had
      been prescribed rifampicin, isoniazid sodium methanesulfonate (IHMS), and
      ethambutol for pulmonary tuberculosis, and ursodesoxycholic acid for alcoholic
      liver dysfunction. The chest HRCT revealed diffuse ground-glass attenuation with
      interlobular interstitial thickening. BALF showed lymphocytosis, and TBLB
      revealed organizing pneumonia. All medications were interrupted, and his
      respiratory failure and chest HRCT findings were improved. He started again
      medications excluding IHMS, his condition continued to improve further. DLST to
      causative IHMS was negative with peripheral blood lymphocytes, but was positive
      with lymphocytes from BALF. Therefore, we diagnosed this case as having IHMS
      induced interstitial pneumonia. In the past, 5 cases of isoniazid induced
      interstitial pneumonia were reported, but IHMS induced interstitial pneumonia has
      not been reported. Clinicians need to be aware of drug induced interstitial
      pneumonia by anti-tuberculosis drugs including IHMS in patients receiving anti
      tuberculosis drugs.

PMID- 12806984
TI  - [A case of tuberculous pericarditis, the diagnosis of which was complicated by
      the delay in the rise of adenosine deaminase in the pericardial effusion].
AB  - An 81-year-old man was admitted to our hospital because of pericardial effusion
      and sputum PCR positive for Mycobacterium (M.) tuberculosis. Since adenosine
      deaminase (ADA) value of the pericardial effusion was not high and the sputum
      smear and culture were negative, anti-tuberculous therapy was not started. Two
      months later he was admitted again because of high fever and cardiomegaly. Chest
      computed tomography showed deterioration and the sputum culture revealed M.
      tuberculosis. The ADA value of the pericardial effusion which was not high at the
      first admission, was elevated in the second admission, and the diagnosis was made
      as tuberculous pericarditis two months later. We had better start anti
      tuberculous therapy at the first admission, in spite of low value of ADA, as his
      pericardial effusion showed lymphocyte predominance.

PMID- 12806985
TI  - [Importance of sugar chain functions and their characterization].

PMID- 12806986
TI  - [Glycobiology basics: glycoproteins].

PMID- 12806987
TI  - [Glycobiology basics: proteoglycans].

PMID- 12806988
TI  - [Glycobiology basics: glycolipids].

PMID- 12806989
TI  - [Regulation of growth and differentiation by oligosaccharides].

PMID- 12806990
TI  - [Involvement of acidic carbohydrates in learning and memory].

PMID- 12806991
TI  - [Function of fucosyltransferases].

PMID- 12806992
TI  - [Sialic acid modification].

PMID- 12806993
TI  - [Function of gangliosides].

PMID- 12806994
TI  - [Biology of glucosylceramide synthase: importance of lipid glycosylation].

PMID- 12806995
TI  - [Functions of Gal 3-sulfotransferases].

PMID- 12806997
TI  - [N-glycan as a signal for proteolysis].

PMID- 12806996
TI  - [Glycoprotein quality control for newly synthesized proteins in the endoplasmic
      reticulum].

PMID- 12806998
TI  - [Protease modified by sugar chain: beta 1-6 branching and matriptase].

PMID- 12807000
TI  - [Biosynthesis of GPI-anchored proteins].

PMID- 12806999
TI  - [BACE1 and glycosyltransferases].

PMID- 12807001
TI  - [Initiation of mucin glycosylation].

PMID- 12807002
TI  - [Genes responsible for sugar chain synthesis in yeast].

PMID- 12807004
TI  - [Proteoglycan core glycosyltransferases].

PMID- 12807003
TI  - [Molecular diversity and biological functions of proteoglycan sulfotransferase].

PMID- 12807005
TI  - [Hyaluronan synthase].

PMID- 12807006
TI  - [Regulation of cellular function by mammalian sialidase].

PMID- 12807007
TI  - [Nucleotide-sugar transporters].

PMID- 12807008
TI  - [Glycoproteomics of C. elegans].

PMID- 12807009
TI  - [Systematic analysis of glycome functions of the nematode Caenorhabditis
      elegans].

PMID- 12807010
TI  - [Drosophila glycobiology].

PMID- 12807011
TI  - [Non-mammalian model systems for functional studies of heparan sulfate
      proteoglycans].

PMID- 12807012
TI  - [Immunological function of mannan-binding protein].

PMID- 12807013
TI  - [Galectin].

PMID- 12807015
TI  - [Functions of sialic acids-binding lectins, Siglecs].

PMID- 12807014
TI  - [Diverse function of macrophage galactose-type C-type lectin (MGL)].

PMID- 12807017
TI  - [Recent advances in the study of lymphocyte homing involving selectins and CD44].

PMID- 12807016
TI  - [Role of glycoconjugates in egg-sperm interaction].

PMID- 12807018
TI  - [Carbohydrate recognition modulates cell proliferation].

PMID- 12807019
TI  - [A specific ligand of V alpha 14 NKT cells and its presentation].

PMID- 12807020
TI  - [Muscular dystrophies due to defective O-mannosylation of alpha-dystroglycan].

PMID- 12807021
TI  - [Receptor binding specificity of influenza virus and its budding from the host
      cells].

PMID- 12807022
TI  - [Keratan sulfate biosynthesis and macular corneal dystrophy].

PMID- 12807023
TI  - [XGalT-1 involved in the synthesis of glyosaminoglycans of proteoglycans and
      Ehlers-Danlos syndrome (progeroid type)].

PMID- 12807024
TI  - [Cytokinesis inhibition by glycosphingolipid, psychosine].

PMID- 12807025
TI  - [Lipid rafts and glycoconjugates].

PMID- 12807026
TI  - [Recruitment of the neutral ceramidase to plasma membranes as a type II integral
      membrane protein by O-glycosylation of mucin-like domain--new technology for
      conversion of soluble proteins to type II integral proteins of plasma membranes].

PMID- 12807027
TI  - [Insulin resistance in type 2 diabetes as a microdomain syndrome].

PMID- 12807028
TI  - [Stable-isotope-assisted NMR analyses of glycans].

PMID- 12807029
TI  - [Mass spectrometry for glycoproteomics I].

PMID- 12807030
TI  - [Mass spectrometry for glycoproteomics II].

PMID- 12807031
TI  - [DNA microarrays of glyco chain related genes].

PMID- 12807032
TI  - [Frontal affinity chromatography].

PMID- 12807033
TI  - [Construction of saccharide library by cells].

PMID- 12807034
TI  - [Automated glycosynthesizer "Golgi" by mimicking biosynthetic process].

PMID- 12807035
TI  - A bird in the hand. By implementing resources already available, healthcare
      organizations have streamlined workflow, reduced costs and improved outcomes for
      patients.

PMID- 12807036
TI  - Lights, camera--and millions in action. West Coast health plan uses information
      technology to increase its claims volume, reduce labor expenses and become a
      provider of outsourced services where it used to be a consumer.

PMID- 12807037
TI  - Revenue recovery on a grand scale. Rhode Island healthcare system uses contract
      management technology and services to recover unpaid millions.

PMID- 12807038
TI  - Forty to one. Healthcare organization collects on the uncollectable and gains
      huge ROI using Internet search service.

PMID- 12807039
TI  - Less invasive stabilization system (LISS) in the treatment of distal femoral
      fractures.
AB  - The treatment of distal femoral fractures has been associated with a high rate of
      complications for a long time. Although implants and surgical techniques have
      improved, plate osteosynthesis and intramedullary nailing have been accompanied
      by a high occurrence of infection, non-union and malalignment. The treatment of
      soft tissue envelopes using "biological" osteosynthesis and minimally invasive
      approaches has resulted in a decrease in complication rates and ultimately led to
      the concept of the less invasive stabilization system (LISS). This is an
      extramedullary-applied, internal fixator shaped according to the implantation
      site anatomy, with minimal invasiveness. The purpose of this study was to present
      this new surgical technique and draw attention to its advantages and importance.
      Although this is not a scientific paper, we hope to provide enough evidence of
      the LISS usefulness. The main LISS components include multiple-fixed angle screws
      and an insertion handle for submuscular sliding of a fixator and placement of
      percutaneous, self-drilling, unicortical screws for fixation of the diaphyseal
      fracture fragments. The LISS has been designed to preserve periosteal perfusion
      and to facilitate a minimally invasive application. Since the first implantation
      of the LISS, only a few studies have been published on its use in treatment of
      distal femoral fractures. The rate of infection has been low, ranging from 0 to
      4%. The rate of delayed union has been between 2.4 and 6.1%, but delayed unions
      do not necessarily lead to secondary bone grafting or repeat osteosynthesis as
      the LISS has a high and lasting stability. When the LISS is used, bone grafting
      is rarely necessary (0 to 1.6% in primary and 0 to 5% in secondary grafting).
      Also implant failure differs from the failure of plate osteosynthesis because,
      with the use of LISS, no screw loosening or secondary malalignment occurs.
      Implant failures (up to 7.4%) were recorded particularly at the time of LISS
      introduction in surgical practice and were attributed to the technique of
      implantation rather than to the implant itself. Good treatment outcomes have been
      reported. The average knee flexion has been 103 degrees and 107 degrees. In 72.5%
      of the patients, flexion has been more than 90 degrees and an extension lag of >
      or = 10 degrees has been found in only 7.5% of all cases. The average Neer score
      has ranged from 73.9 to 77.2 points. In conclusion, the LISS is a useful implant
      for treatment of distal femoral fractures, especially when bone quality is poor.
      Infection, delayed union and non-union rates are low, as shown by yet unpublished
      data from our clinic. Primary bone grafting, which is rarely necessary with this
      system, is carried out only when there is a great bone loss. Implant failure,
      such as screw loosening or secondary malalignment, is not seen.

PMID- 12807040
TI  - [Bone grafts in hip prosthesis revisions].
AB  - PURPOSE OF THE STUDY: We describe the collection, storage and examination of
      allogenic bone grafts and their use in revision hip arthroplasty, indicated
      because of acetabular loosening, that involved either an uncemented cup or an
      augmentation device with a cemented cup according to the extent and nature of
      acetabular defects. MATERIAL: Allogenic bone grafts, usually long bones, were
      collected from deceased humans within 12 hours of death. They were processed
      according to the standards of US tissue banks. Using ELISA, the blood of each
      donor was serologically examined for antibodies against selected antigens (HIV I,
      HIV II, syphilis, HbsAg, HCV, and p24HIV I, HTLV I and II, and HbcAg, if
      required). Microbiological examination of each bone sample was also included. The
      samples were kept in a quarantine box until the examination results were known.
      When these were negative, the bones were cut, under aseptic conditions, to obtain
      parts (condyle, metaphysis, diaphysis, patella, etc.) weighing from 80 to 150 gr.
      Subsequently, another quality check, involving microbiological and histological
      examination, was performed. The allografts were stored at -80 degrees C. METHODS:
      Between October 1999 and October 2000, 67 revision total hip replacements were
      performed. Of these, allogenic bone grafting was used for acetabular
      reconstruction in 30 cases (45%). The average amount of graft tissue per
      operation was 107 gr (range, 43 to 163 gr). Eleven grafts had been harvested from
      the tibial condyle, nine from the trochanters, eight from the femoral condyle and
      two from the patella. The graft bone, ground into coarse chips, was washed with
      an antibiotic solution. Two techniques were used in graft implantation. 1)
      Impaction grafting, under pressure, of the acetabulum whose surface was free from
      any granulation tissue and scratched to make the bone bleed, and implantation of
      a cemented cup (LOR or Spotorno CLS). 2) Filling of large defects with a bulk of
      allograft bone chips, using an augmentation ring, mesh or Burch-Schneider cage,
      and implantation of a cemented polyethylene acetabular component. Uncemented
      implants were used in 17 and cemented cups with an augmentation device in 13
      cases. The hips were checked by X-ray at 3, 6 and 12 months and then at yearly
      intervals. RESULTS: In the postoperative period of 26 to 38 months, an early
      recurrent infection led to temporary removal of the implant in one case, one hip
      showed superficial infection that responded to therapy and there was one case of
      aseptic acetabular loosening. A recurrent dislocation led to femoral stem
      exchange for a modular component with a longer neck in one case. The remaining 28
      cases showed good incorporation of the graft without any signs of implant
      migration. DISCUSSION: Segmental defects of the acetabulum can be treated by
      implantation of specific types of acetabular cups or by massive bone grafting.
      Cavitary defects can be filled with cancellous allograft bone or bioactive,
      artificial materials. We prefer morselized allograft bone from the tissue bank
      and this was used in 45% of repeat surgeries for failure of the acetabular
      component. An uncemented cup is more convenient, supposing sufficient primary
      stability can be ensured. When defects are extensive, augmentation devices and
      filling with graft bone are necessary. Cadaver allografts offer advantages over
      autologous bone because they are available at any amount and thus enable us to
      avoid extensive damage to the iliac crest by autologous tissue harvesting.
      Cadaver grafts are bones of good quality, free from degenerative or dystrophic
      changes because they are usually taken from young subjects. The size of 7 to 10
      mm is optimal because it permits the grafts to maintain both structure and
      strength. The strict procedure of sample collection and examination minimizes the
      risk of infection transfer. The progress of graft bone ingrowth was evaluated on
      radiographs that showed incorporation of allograft into the surrounding bone
      during 3 to 6 months and no radiolucent areas at host bone-implant contact.
      CONCLUSIONS: Our patients showed good allogenic bone ingrowth in relation to the
      acetabular bed and good bone restructuring and incorporation in relation to the
      implant. Neither mechanical failure of implants nor graft rejection were
      recorded. The risk of infection transfer was low and comparable with routine
      blood transfusion. The necessary prerequisite for revision hip arthroplasty is a
      well-operating bone tissue bank.

PMID- 12807041
TI  - [Results of lumbar diskectomy].
AB  - PURPOSE OF THE STUDY: We evaluated the outcomes of lumbar discectomies in
      relation to the presence or absence of degenerative spinal lesions and the
      surgical treatment used in order to determine the extent to which these factors
      influence the result of treatment. MATERIAL: Patients who were treated by
      discectomy in the period from January 1, 1994, to July 7, 1998, were contacted. A
      total of 132 subjects received the Oswestry questionnaire (in two copies) in
      February 2002 and 100 of them, 62 men and 38 women, were included in the final
      evaluation. The average age of the patients at the time of surgery was 42.86
      years (range, 15 to 69 years). The average follow-up period was 3.22 years. All
      patients underwent preoperative neurological check-up and examination by X-ray,
      contrast perimyelography, magnetic resonance imaging or computer tomography. The
      surgical procedure involved either microdiscectomy according to Caspar or
      conventional open discectomy. METHODS: The patients were allocated to four groups
      on the basis of the presence or absence of degenerative lesions shown by pre
      operative or intra-operative findings and of the surgical treatment used. Each
      group was evaluated individually. Group 1 comprised 15 patients without
      degenerative lesions and group 2 included 19 patients with degenerative lesions;
      both groups were treated by the Caspar method. Groups 3 and 4 were treated by
      open discectomy and consisted of 32 patients without and 34 patients with
      degenerative lesions, respectively. The patients reported their pre- and post
      operative complaints retrospectively, using a separate copy of the Oswestry Low
      Back Pain Disability Quiestionnaire, Version 1.0, for each period. RESULTS: In
      the whole sample, the average improvement estimated by the Oswestry Disability
      Index (ODI) was 30.32% in the year 2002, as compared with 54.15% before surgical
      treatment. The best outcome, improvement by 45.87%, was in group 1. Groups 2, 3
      and 4 showed improvements by 31.95%, 30.35% and 22.38%, respectively. DISCUSSION:
      The Oswestry questionnaire has become a widely-used instrument for evaluation of
      complaints in patients with spinal disorders. Its universal application enabled
      us to compare the results of different studies. The presence of degenerative
      lesions was responsible for less successful outcomes of both the Caspar
      microdiscectomy and open discectomy. It remains to be answered to what extent
      these poorer outcomes in spines with degenerative lesions are related to the
      instability of the segments treated. However, it is apparent that the Caspar
      microdiscectomy improved the patients' conditions more than open discectomy.
      CONCLUSIONS: The average 30.32% decrease in ODI score from 54.15% before the
      surgical tree of intervertebral discs herniation, as evaluated at an average of
      3.22 years after surgery, is regarded as a good outcome. The Oswestry
      questionnaire generally permits a reliable assessment of patient complaints. In
      this study, a Czech translation of Version 2.0 of this questionnaire is presented
      and recommended for use. The presence of serious degenerative spinal lesions
      makes the outcomes of discectomy less satisfactory. Prospects for the approach
      that combines discectomy with fusion can be assessed in patients whose
      indications are well defined and complaints exactly evaluated.

PMID- 12807042
TI  - [Disarticulation of the knee joint].
AB  - PURPOSE OF THE STUDY: The authors report their experience with exarticulation in
      the knee joint, describe the relevant surgical procedure, assess the outcomes of
      different modifications of the surgical treatment and emphasize the advantages of
      the stump following exarticulation in the knee joint. MATERIAL: The sample
      included 19 patients, 13 women and 6 men, operated on in the period from 1987 to
      2001. One of the women had bilateral surgery. Their average age at the time of
      surgery was 48 years, the range was 5 to 82 years. In most of the patients,
      exarticulation in the knee joint was indicated because of a malignant tumor in
      the crux region that could not be treated by any radical but, at the same time,
      limb-saving procedure. Other indications included an infected allograft of the
      tibia, chronic osteomyelitis of the tibia complicated by spinocellular carcinoma
      in a fistula, a stump after high amputation in the tibia that could not be fitted
      with a prosthesis, chronic lymphedema and diabetic microangiopathy. METHODS:
      Exarticulation is an amputation of the peripheral part of a limb in a joint,
      i.e., without cutting bone. The authors used a modified Rogers' procedure. Under
      the use of a tourniquet, a ventral incision, 10 cm long, was run from the
      articular fissure level distally and a dorsal incision, 5 cm long, was cut distal
      to the articular fissure. This produced a longer ventral and a shorter dorsal
      flap. The subsequent procedure included the discission of the ligamentum patellae
      at the tibial attachments, the articular capsule, m. sartorius, m. gracilis, m.
      semitendinosus, m. semimembranosus and biceps femoris, all cut at their distal
      attachments, as well as the tractus iliotibialis. The collateral and cruciate
      ligaments were incised at their femoral attachments. After dissection of the
      neuro-vascular bundle, the vessels were incised and double ligated. The n.
      tibialis and n. peronaeus were infiltrated with mesocaine and cut through. Then
      the m. popliteus, ligamentum popliteum arcuatum and the two heads of the m.
      gastrocnemius were incised and the crux separated. After removal of the pneumatic
      tourniquet, bleeding was arrested. The condyles, patella and synovialis were left
      intact. The ligamentum patellae was sutured to the tendons of the m.
      semimemranosus, m. semitendinosus and biceps femoris. The m. satorius and m.
      tractus iliotibialis were sutured to the extensor apparatus. The layer after
      layer was sutured with individual stitches and two Redon's drains were inserted
      below the fascia. RESULTS: Five patients were referred back to the initial
      hospital. Of six patients who died, five developed complications due to
      dissemination of the underlying malignant disease and one died of causes
      unrelated to the major disease. Eight patients were followed up at regular
      intervals. Of these, seven were satisfied with their stump and only one patient
      complained of pressure sores and therefore changed prosthetic care. Patients'
      complaints that would lead to repeat operations or amputation in the femur were
      not recorded. DISCUSSION: The surgical technique described is fast, gentle in
      terms of tissue damage and relatively easy to perform. All patients in the group
      showed good healing. The authors point out that the stump achieved by
      exarticulation has good weight-bearing qualities because of a large surface
      controlled by strong musculature that can maintain muscular balance and control
      the rotation of a prosthesis. The results of this study are in agreement with the
      data published in the English, German and Russian literature. In the Czech
      literature, this issue has not been reported yet. CONCLUSIONS: The advantages of
      exarticulation in the knee joint are as follows: quick, gentle and uncomplicated
      surgical procedure with low blood losses; good potential for per primam healing;
      high quality of the stump surface to be fitted with a prosthesis; current
      availability of good quality prostheses that are easier to fit than those applied
      after high amputation in the crux with a stump less than 11 cm or after low
      amputation in the femur.

PMID- 12807043
TI  - [Treatment of calcaneal fractures using the medial approach for open reduction].
AB  - PURPOSE OF THE STUDY: A comprehensive evaluation of the treatment of calcaneal
      fractures by open reduction is presented. The long-term results are compared with
      the relevant literature data. MATERIAL: In the period from 1987 to 2000, 60
      displaced fractures of the calcaneus were treated in 51 patients. Of these, 49
      patients suffered the fracture by falling from a height, which is generally the
      most common cause. Only two patients were injured during sports activities.
      Thirty eight injuries were classified as fractures of the joint depression type
      and 22 as fractures of the tongue type. The patients had surgery on the day they
      sustained the injury or after edema had subsided, if this was present on
      admission. The interval between injury and surgery was 4.6 days on the average.
      The fracture was fixed with Kirschner's wires (Kw) in 53 cases, a Kirshcner's
      wire and a hook-nail in five cases and a Kirchner's wire and a spongious screw in
      two patients. In May 2001, 23 patients were available for evaluation after a
      follow-up period of 6 to 120 months. METHODS: The patients underwent clinical and
      radiographic examination and filled a questionnaire. The fracture type was
      defined on the basis of the Essex-Lopresti classification system. Outcomes were
      scored according to the Creighton-Nebraska Health Foundation rating system that
      assessed pain, range of motion, edema, a change in shoe size, patient's activity
      after therapy termination and return to a job. RESULTS: In May 2001, 23 patients,
      with a follow-up ranging from 6 to 120 months were checked up. Of them, 20
      (86.9%) had neither clinical manifestations nor subjective complaints. Three
      patients retired because of persisting complaints, two with disability pensions
      and one with an old-age pension. A total of 19 patients were evaluated by the
      Creighton-Nebraska Health Foundation rating system. The average score was 90.8
      points. The results were excellent in 15 patients, good in three and poor in one
      patient. The complications reported by the patients included superficial
      infection in two, thromboembolic disease in one, and hypesthesia on the medial
      side of the leg in two patients. DISCUSSION: The optimal mode of treatment in
      dislocated intra-articular fractures of the calcaneus still remains open to
      discussion. Should conservative or surgical therapy be used? In agreement with
      others, the authors preferred early surgical intervention. This facilitated a
      better congruence of the dorsal articular surface. The average remaining
      dislocation of the articular surface was 1.1 mm in surgically treated as against
      the average of 4.7 mm in conservatively treated patients. It was possible to
      restore the length, height and width, and the correct axial position of the
      calcaneus by this surgery from the medial approach. However, in indicated cases,
      the procedure required an additional intervention from the lateral approach
      through a mini-incision. As reported in the literature, other authors have
      achieved comparable, or even better results but on the basis of either the
      lateral or the plantar approach. The application of primary spongioplasty or
      primary arthrodesis of the subtalar joint is discussed. The advantages of
      preoperative examination by computer-assisted tomography are emphasized.
      CONCLUSIONS: Good outcomes of the treatment of intra-articular, dislocated
      calcaneal fractures depend on a correct shape and position of the dorsal
      articular surface of the calcaneus. The open reduction procedure from the medial
      approach based on the principles of McReynold's technique allowed us to
      accomplish both these criteria.

PMID- 12807045
TI  - Sacroiliac joint dislocation in 11 years old boy treated by open reduction and
      internal fixation.
AB  - Pelvic fractures in children are relatively rare, especially unstable pelvic ring
      disruptions. Generally, nonoperative treatment has been recommended for children
      with these injuries because healing is rapid and remodeling extensive in
      children. Treatment generally is a period of recumbency until the fractures heal,
      followed by gradual weight bearing. Various methods of operative treatment were
      advised by some authors. They reported a higher incidence of residual problems
      after pelvic disruption such as malunion, hemipelvic undergrowth, low back pain
      and leg length discrepancy. These authors are of opinion, that principles of
      treatment should not differ from the treatment of adults if the pelvis is
      unstable and if there is significant displacement. We describe a case of a
      vertically unstable pelvic ring injury with sacroiliac joint dislocation and limb
      length discrepancy in 11 year old boy. Patient was received for treatment 14 days
      after trauma. He was treated by open reduction from anterior approach and
      percutaneous screw fixation. In one year follow-up he has very good functional
      result.

PMID- 12807044
TI  - [Fractures of the distal radius. Part 1: statistical evaluation of the patient
      group].
AB  - PURPOSE OF THE STUDY: Distal radial fracture is one of the most frequent skeletal
      injuries in the human population. Probably because of this common occurrence, it
      has long been underestimated and treated as a trivial injury, with the resulting
      40% poor outcome. The aim of this study was to analyze relevant characteristics,
      fracture types and subsequent treatment in patients with distal radial fractures
      in a one-year follow-up, and to suggest procedures for achieving the best
      functional results. MATERIAL: A total of 383 patients older than 15 years were
      treated in our department in 1998. The evaluation of treatment outcomes was based
      on a special questionnaire and the results of a standard system of check-ups.
      METHODS: In each patient, the basic characteristics (age, gender, mechanism of
      injury, period between injury and treatment, etc.), type of fracture and kind of
      treatment were recorded. The fractures were distributed to groups according to
      the Fernandez and AO classifications and compared according to selected criteria.
      RESULTS: Our group consisted of 103 men and 280 women; the mean age was 61.2
      years and range 15 to 97 years. The highest incidence of fractures was recorded
      in women after menopause; 90% of all patients were women older than 60 years. It
      was possible to determine the type of fracture in 326 patients who had complete
      radiographic data. DISCUSSION: The results of this study confirmed the foreign
      literature data. Distal radial fractures are the most common skeletal injuries
      and affect women, particularly those between 50 and 80 years, three-times more
      frequently than men. Osteoporosis after menopause is the main factor involved. In
      men, on the other hand, the highest number of fractures was found in younger age
      categories. CONCLUSIONS: The evaluation of our patient group gave results
      comparable with those reported in the literature. It showed that distal radial
      fractures, in conjunction with fractures of the proximal humerus and the proximal
      femur, are the most frequent fractures particularly in elder women. Their
      treatment, therefore, involves both medical and social aspects. The analysis of
      treatment of distal radial fractures is under progress and the results will be
      published as Part II of our study.

PMID- 12807046
TI  - [Orthopedic treatment of a boy with Larsen's syndrome].
AB  - A case of Larsen's syndrome in a boy is presented. The syndrome is characterized
      by flattened facies, multiple congenital dislocations and foot deformities as a
      result of connective tissue maldevelopment during gestation. The importance of
      early intensive conservative therapy is emphasized. In the case reported,
      conservative therapy led, in the first stage, to the management of subluxation of
      both hips and improvement in left foot position and in the state of both knees.
      Subsequently, dislocations of the right and the left knee joint were surgically
      treated at 16 and 20 months, respectively, by reduction and transfixation with
      Kirschner's wires according to Niebauer and King. After six weeks of plaster
      immobilization, the wires were removed and the knee position was corrected with
      laminate splints. The authors point out that the syndrome is often associated
      with cardiovascular anomalies. Although these were not present in the case
      reported, due to the repeated occurrence of pericardial exudates from 2 years of
      the child' age, it was not possible to manage his left foot (pes equinovarus)
      surgically earlier than at 36 months. For that procedure, the method of
      posteroplantar release was used. The authors also discuss the occurrence of
      vertebral anomalies in Larsen's syndrome that may lead to cervical kyphosis and,
      potentially, to cervical spine instability. In our case, the signs of kyphosis
      were observed in the C1-C3 region but magnetic resonance imaging did not show any
      signs of either myelopathy or narrowing of the spinal canal. The intensive
      conservative and surgical treatment with subsequent thorough rehabilitation
      enabled the patient to stand up and walk without any support or orthotics. The
      fact that the boy was able to integrate in healthy children's playgroups can be
      considered a great achievement of orthopedic therapy.

PMID- 12807049
TI  - Shameless self-promotion.

PMID- 12807047
TI  - [Traumatic spondylolisthesis of L5-S1].
AB  - Pure traumatic bilateral lumbosacral dislocation is a rare injury with just eight
      cases reported in the literature. This condition occurred also in 36-year-old
      man, who was struck into the lower back by a falling tree, during a woodcutting,
      at the moment when he was kneeling and his spine was flexed. Neurological
      examination showed no signs of spinal nerves injury. X-ray examination of the
      lumbosacral spine revealed the presence of a 40% anterior dislocation of L5 over
      S1 with locked facets and multiple fractures of transverse processes. Computer
      tomography confirmed these findings and also revealed massive medial L5-S1 disc
      herniation. Surgery performed 9 days after the injury consisted of L5
      laminectomy, L5-S1 discectomy and segmental reduction and stabilization with
      transpedicular screws. Posterior lumbar interbody fusion was carried out using
      titanium PLIF-blocks. The patient healed without complications. At a 24-month
      follow-up he was without any subjective complaints, neurologically asymptomatic
      and without restriction of mobility in the lumbosacral spine. He was able to
      resume his previous work. This rare case is discussed in a view of the relevant
      literature, biomechanics of trauma and the appropriate therapy with an emphasis
      on open reduction and internal fixation techniques.

PMID- 12807050
TI  - Glucosamine for arthritis.

PMID- 12807051
TI  - Combination agents for diabetes.

PMID- 12807053
TI  - Patient information. Reflux: what you need to know.

PMID- 12807052
TI  - Varicose veins. Treatment warranted for medical as well as cosmetic reasons.

PMID- 12807054
TI  - Extrapyramidal effects of antiemetics. Identifying and managing patients at risk.

PMID- 12807055
TI  - Planning your private practice. Setting realistic expectations.

PMID- 12807056
TI  - Developing a business plan. Getting down to specifics.

PMID- 12807057
TI  - Financing a private practice. Investigating the options.

PMID- 12807058
TI  - Marketing your practice. Strategies that work.

PMID- 12807060
TI  - Cardiac rehabilitation. The right fit for women.

PMID- 12807059
TI  - Liver disease and HIV. Hepatitis is an ongoing threat.

PMID- 12807061
TI  - Lyme disease in children. An overview.

PMID- 12807062
TI  - They wound, work and womanize to mask depression. Boys don't cry.

PMID- 12807063
TI  - Participative ethical decision making. A model for primary care.

PMID- 12807064
TI  - Priorities in behavioral science education: views of practicing family
      physicians.
AB  - BACKGROUND AND OBJECTIVES: The behavioral science curriculum in family practice
      residency programs consists of a wide range of diverse topics. Because of time
      limitations, not all topics receive equal emphasis. The goal of the present study
      was to replicate a previous study with family physicians practicing in a
      different geographical area. METHODS: Questionnaires were mailed to a sample of
      543 family physicians in Mississippi. Respondents were asked to rate each of 28
      behavioral science topics according to the priority to be given in residency
      education. RESULTS: One hundred eighty-five surveys were returned for a 34%
      response rate. The rank order of topics in the present study was highly similar
      to the rank order in the original study. Female physicians had higher overall
      mean ratings. CONCLUSIONS: This sample of family physicians in Mississippi
      provided similar ratings to those in a previous study of family physicians
      trained and/or practicing in Colorado. The results support that, regardless of
      geographic location and practice characteristics, family physicians hold similar
      opinions about which behavioral science topics should receive highest priority in
      residency training. The behavioral science curriculum in family practice
      residency programs consists of a wide range of diverse topics. Because of time
      limitations, not all topics receive equal emphasis. Published resources provide
      helpful lists of topics and teaching strategies but do not specify which areas
      should be given priority. Consequently, behavioral science teachers may have
      difficulty prioritizing the topics because there is no agreement on the core
      competencies to be given highest priority in residency education. In a previous
      study, investigators sent a survey to practicing family physicians to determine
      the topics of behavioral science considered to be most important in residency
      education. The physicians were able to identify specific topics to be given
      higher priority. While these previous results were useful, the study was limited
      by the homogeneity of the sample. All the family physicians had trained or were
      currently practicing in the state of Colorado. The goal of the present study was
      to replicate the original study with family physicians practicing in a different
      geographical area.

PMID- 12807065
TI  - The new epidemic.

PMID- 12807066
TI  - Legislative call to action.

PMID- 12807067
TI  - Malpractice insurance in Mississippi.

PMID- 12807068
TI  - Looking back: the use of radium in the treatment of myoma uteri and myopathic
      hemorrhages in 1920.

PMID- 12807069
TI  - [Cancer of the uterine cervix is the second most frequent gynecologic pathology
      in the world].

PMID- 12807070
TI  - [Invasiveness of cancers of the uterine cervix].

PMID- 12807071
TI  - [The value of emission computed tomography with 18 F-fluorodeoxyglucose (PET scan
      with 18FDG)].

PMID- 12807072
TI  - [Treatment of the uterine cervix].

PMID- 12807073
TI  - Prenatal detection of fetal aneuploidy by sonographic ear length.
AB  - OBJECTIVE: To determine the usefulness of a fetal ear length nomogram in the
      prenatal detection of fetal aneuploidy and to determine whether ear smallness in
      cases of aneuploidy is a primary or secondary event. METHODS: Ear lengths of 447
      singleton fetuses (October 1996 to October 1997)were prospectively evaluated
      between 14 and 41 weeks to establish a nomogram created by modeling the mean and
      SD separately. Records of aneuploid fetuses were retrospectively reviewed, and
      their ear lengths were plotted against the nomogram to determine detection rates,
      with ear length in or below the 10th and 50th percentiles for a given gestational
      age and biparietal diameter used as abnormal cutoffs. RESULTS: The nomogram for
      fetal ear length measurements provided sufficient data to derive the 10th, 50th,
      and 90th percentiles on the basis of gestational age and biparietal diameter. The
      ear length of euploid fetuses was significantly correlated with gestational age
      (R2 = 0.96; P < .001) and biparietal diameter (R2 = 0.95; P < .001). From 96
      aneuploid fetuses identified, 63 had ear lengths in or below the 10th percentile
      for gestational age (sensitivity, 66%). When using ear length against biparietal
      diameter, the sensitivities for all aneuploid fetuses for cutoffs at or below the
      10th and 50th percentiles were 43% (40 of 93) and 83% (77 of 93), respectively.
      CONCLUSIONS: Most aneuploid fetuses have sonographically small ears (< or = 10th
      percentile for gestational age). This smallness is not entirely related to
      overall small fetal size, but in almost half the cases, the fetal ear length is
      disproportionately smaller than the biparietal diameter.

PMID- 12807074
TI  - Prenatal detection of fetal trisomy 18 through abnormal sonographic features.
AB  - OBJECTIVE: To describe the prenatal detection of fetal trisomy 18 through
      abnormal sonographic features and to determine the sensitivity of sonographically
      detecting fetuses with trisomy 18. METHODS: All genetic and cytogenetic records
      of fetuses with trisomy 18 were reviewed retrospectively (1992-2002). From these,
      singleton fetuses who had prenatal sonography at our unit were identified. The
      maximal numbers of individual abnormalities from 1 sonographic examination (not
      limited to type of organ system) were recorded. Each abnormality was classified
      as major, minor, or "other," and each organ system was classified as abnormal
      only once, regardless of the number of individual abnormalities identified in
      that system. The sensitivity of sonography in detecting abnormalities of trisomy
      18 was determined. RESULTS: Of 38 fetuses identified with trisomy 18, all had 4
      or more prenatally detected sonographic abnormalities (sensitivity of sonographic
      detection of fetuses with trisomy 18, 100%). The median number of abnormalities
      per examination was 8 (range, 4-19). Sonographically detected major abnormalities
      were cardiac (84%; n = 32), central nervous system (87%; n = 33),
      gastrointestinal (26%; n = 10), and genitourinary (16%; n = 6). Sonographically
      detected minor abnormalities were short ear length below the 10th percentile for
      gestational age (96%; n = 26/27), upper extremities and hands (95%; n = 36),
      lower extremities and feet (63%; n = 24), and face (53%; n = 20). Fifty percent
      (19 of 38) had choroid plexus cysts identified, but this was never an isolated
      finding. CONCLUSIONS: In experienced hands, the sensitivity of detecting fetal
      trisomy 18 on prenatal sonography is 100%, and all cases will have multiple
      anomalies visualized.

PMID- 12807075
TI  - Gabapentin in geriatric mania.
AB  - There is little available information on anticonvulsant treatment of mania in
      elderly patients. Seven elderly patients, each in a manic episode, were treated
      with gabapentin. All 7 patients experienced improvement in manic symptoms, with
      minimal to no side effects. They received gabapentin in combination with
      antipsychotic medications, and in 1 case in combination with valproate.
      Gabapentin appears to be a safe and effective treatment in geriatric mania when
      combined with antipsychotic medications or valproate. Gabapentin appears to be
      well tolerated with no major adverse drug interactions or side effects in elderly
      manic patients. This case series suggests that controlled studies are warranted
      to examine gabapentin's efficacy and side effects, particularly as an adjunctive
      medication, in geriatric mania.

PMID- 12807076
TI  - Meeting the challenges of a changing profession.

PMID- 12807077
TI  - Search for protein partners of mitochondrial single-stranded DNA-binding protein
      Rim1p using a yeast two-hybrid system.
AB  - RIM1 is a nuclear gene of the yeast Saccharomyces cerevisiae coding for a protein
      with single-stranded DNA-binding activity that is essential for mitochondrial
      genome maintenance. No protein partners of Rim1p have been described so far in
      yeast. To better understand the role of this protein in mitochondrial DNA
      replication and recombination, a search for protein interactors by the yeast two
      hybrid system was performed. This approach led to the identification of several
      candidates, including a putative transcription factor, Azf1p, and Mph1p, a
      protein with an RNA helicase domain which is known to influence the mutation rate
      of nuclear and mitochondrial genomes.

PMID- 12807078
TI  - Severe acute respiratory syndrome--Taiwan, 2003.
AB  - On April 22, 2003, the Taiwan Department of Health (DOH) was notified of seven
      cases of severe acute respiratory syndrome (SARS) among health-care workers
      (HCWs) at a large municipal hospital in Taipei (hospital A). Subsequent cases at
      eight hospitals have been associated with exposures at hospital A. Previously,
      all reported cases had been associated with persons recently returning to Taiwan
      from SARS-affected regions. This report summarizes epidemiologic findings of the
      outbreak in Taiwan and describes the impact of health-care--associated
      transmission of SARS.

PMID- 12807079
TI  - Update: severe acute respiratory syndrome--United States, May 21, 2003.
AB  - CDC continues to work with state and local health departments, the World Health
      Organization (WHO), and other partners to investigate cases of severe acute
      respiratory syndrome (SARS). This report updates SARS cases reported worldwide
      and in the United States and highlights recent modifications to the U.S. SARS
      case definition that define criteria for exclusion of previously reported SARS
      cases and for reporting travel-associated cases of SARS.

PMID- 12807080
TI  - Elevated mortality associated with armed conflict--Democratic Republic of Congo,
      2002.
AB  - In August 1998, citing a need to control insecurity on their western borders,
      Rwanda and Uganda sent troops into the Democratic Republic of Congo (DRC)
      (estimated 2002 population: 51 million). Within 6 months, troops from seven
      neighboring countries were fighting in the DRC, with various Congolese groups
      supporting different invading armies. During 1998-2002, the majority of the
      fighting occurred in the DRC's five eastern provinces (1996 population: 19.9
      million). To assess the impact of the armed conflict on public health, the
      International Rescue Committee (IRC), with support from CDC, conducted a
      nationwide mortality survey to measure DRC's nationwide crude mortality rate
      (CMR) and to compare CMRs in DRC's five eastern provinces with CMRs in the five
      western provinces. This report summarizes the results of the survey, which
      indicate that the overall CMR in the DRC is the highest in the world, with the
      majority of deaths caused by preventable infectious diseases. The findings
      underscore the importance of the ongoing peace process, which appears to have
      contributed to a decrease in mortality rates in eastern DRC, and highlights the
      importance of collecting population-based health data regularly during armed
      conflicts.

PMID- 12807081
TI  - Update: global measles control and mortality reduction--worldwide, 1991-2001.
AB  - Despite international recognition of the high burden of disease associated with
      measles and the existence for 40 years of a safe, effective, and inexpensive
      vaccine, measles remains the leading cause of vaccine-preventable childhood
      mortality. In 1990, the World Summit for Children adopted a goal of vaccinating
      90% of the world's children against measles by 2000 (1). In 2001, the World
      Health Organization (WHO) and the United Nations Children's Fund (UNICEF)
      developed the Global Measles Strategic Plan for 2001-2005. The plan's objectives
      are 1) to decrease the annual number of measles deaths by 50% by 2005 compared
      with 1999 levels (875,000 deaths), 2) to achieve and maintain interruption of
      indigenous measles transmission in large geographic areas with elimination goals,
      and 3) to convene a global consultation in 2005 to review progress and assess the
      feasibility of global measles eradication. In May 2002, the United Nations
      General Assembly Special Session on Children also resolved to reduce measles
      deaths by 50% by 2005 compared with 1999 levels. This report describes progress
      toward eliminating measles worldwide. Data from WHO's Global Burden of Disease
      (GBD) project indicate that approximately 1.7 million vaccine-preventable
      childhood deaths occurred in 2000, of which 777,000 (46%) were attributed to
      measles. The measles deaths occurred overwhelmingly among children living in poor
      countries with inadequate vaccination services. To prevent these deaths, stronger
      political commitment is needed to provide all children worldwide with two
      opportunities for measles immunization.

PMID- 12807082
TI  - Update: adverse events following civilian smallpox vaccination--United States,
      2003.
AB  - During January 24-May 9, 2003, smallpox vaccine was administered to 36,217
      civilian health-care and public health workers in 55 jurisdictions to prepare the
      United States for a possible terrorist attack using smallpox virus. This report
      updates information on vaccine-associated adverse events among civilians
      vaccinated since the beginning of the program and among contacts of vaccinees,
      received by CDC from the Vaccine Adverse Event Reporting System (VAERS) as of May
      9.

PMID- 12807083
TI  - Cluster of severe acute respiratory syndrome cases among protected health-care
      workers--Toronto, Canada, April 2003.
AB  - Infections among health-care workers (HCWs) have been a common feature of severe
      acute respiratory syndrome (SARS) since its emergence. The majority of these
      infections have occurred in locations where infection-control precautions either
      had not been instituted or had been instituted but were not followed. Recommended
      infection-control precautions include the use of negative-pressure isolation
      rooms where available; N95 or higher level of respiratory protection; gloves,
      gowns, and eye protection; and careful hand hygiene. This report summarizes a
      cluster of SARS cases among HCWs in a hospital that occurred despite apparent
      compliance with recommended infection-control precautions.

PMID- 12807084
TI  - Update: severe acute respiratory syndrome--United States, May 14, 2003.
AB  - CDC continues to work with state and local health departments, the World Health
      Organization (WHO), and other partners to investigate cases of severe acute
      respiratory syndrome (SARS). This report provides an update on reported SARS
      cases worldwide and in the United States.

PMID- 12807085
TI  - Post-detention completion of tuberculosis treatment for persons deported or
      released from the custody of the Immigration and Naturalization Service--United
      States, 2003.
AB  - The Advisory Council for the Elimination of Tuberculosis (ACET) recommends the
      post-detention completion of tuberculosis (TB) treatment for persons deported or
      released from the custody of the Immigration and Naturalization Service (INS).
      The completion of TB therapy prevents disease relapse, subsequent transmission,
      and the emergence of drug resistance. Integral to treatment completion are issues
      of security and law enforcement involving persons who under immigration law are
      ineligible for legal admission into the United States. The Health Resources and
      Services Administration's Division of Immigration Health Services (DIHS)
      estimates that approximately 150 TB cases are identified annually among INS
      detainees in the INS service processing centers (SPCs) and contract detention
      facilities. Before transfer or deportation, INS policies require that detainees
      with TB disease receive treatment until they become noncontagious, even if
      treatment is not completed. INS policies are consistent with federal law, which
      does not bar deportation of persons with TB disease before the completion of
      treatment. This report describes three cases that illustrate several issues
      associated with the deportation of patients with incomplete treatment of TB
      disease after detention. These cases highlight the need for interagency
      coordination to ensure completion of treatment for persons being evaluated or
      treated for TB.

PMID- 12807086
TI  - Motivational intervention to reduce alcohol-exposed pregnancies--Florida, Texas,
      and Virginia, 1997-2001.
AB  - Prenatal alcohol use is a threat to healthy pregnancy outcomes for many U.S.
      women. During 1999, approximately 500,000 pregnant women reported having one or
      more drinks during the preceding month, and approximately 130,000 reported having
      seven or more alcohol drinks per week or engaging in binge drinking (i.e., five
      or more drinks in a day). These heavier drinking patterns have been associated
      with fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental
      disorders (ARND). Lower levels of alcohol consumption (i.e., fewer than seven
      drinks per week) also have been associated with measurable effects on children's
      development and behavior. Although the majority of women reduce their alcohol use
      substantially when they realize they are pregnant, a large proportion do not
      realize they are pregnant until well into the first trimester and, therefore,
      might continue to drink alcohol during this critical period of fetal development.
      To reduce alcohol-exposed pregnancies, CDC initiated a multisite pilot study
      (phase I clinical trial) in 1997 to investigate the use of a dual intervention
      focused on both alcohol-use reduction and effective contraception among
      childbearing-aged women at high risk for an alcohol-exposed pregnancy (Project
      CHOICES). This report describes the association between baseline drinking
      measures and the success women have achieved in reducing their risk for an
      alcohol-exposed pregnancy. The analysis compares the impact of the motivational
      intervention at 6-month follow-up on women drinking at high-, medium-, and low
      risk drinking levels. The findings indicate that although 69% of the women in the
      study reduced their risk for an alcohol-exposed pregnancy, women with the lowest
      baseline drinking measures achieved the highest rates of outcome success,
      primarily by choosing effective contraception and, secondarily, by reducing
      alcohol use. Women with higher baseline drinking measures chose both approaches
      equally but achieved lower success rates for reducing their risk for an alcohol
      exposed pregnancy. A randomized controlled trial of the motivational intervention
      is under way to further investigate outcomes of the phase I study.

PMID- 12807087
TI  - Update: adverse events following civilian smallpox vaccination--United States,
      2003.
AB  - During January 24--May 2, 2003, smallpox vaccine was administered to 35,903
      civilian health-care and public health workers in 55 jurisdictions to prepare the
      United States for a possible terrorist attack using smallpox virus. This report
      updates information on vaccine-associated adverse events among civilians
      vaccinated since the beginning of the program and among contacts of vaccinees
      received by CDC from the Vaccine Adverse Event Reporting System (VAERS) as of May
      2.

PMID- 12807088
TI  - Severe acute respiratory syndrome--Singapore, 2003.
AB  - The Singapore Ministry of Health (MOH), with assistance from the World Health
      Organization (WHO), has been investigating an outbreak of severe acute
      respiratory syndrome (SARS). This is a novel condition caused by the SARS
      associated coronavirus (SARS-CoV) and is characterized by both an atypical
      pneumonia and efficient nosocomial transmission. This report summarizes
      epidemiologic features of this outbreak in Singapore, including the influence of
      super spreaders and the national prevention and control strategy.

PMID- 12807089
TI  - Update: severe acute respiratory syndrome--United States, 2003.
AB  - CDC, in collaboration with state and local health departments, the World Health
      Organization (WHO), and other partners, continues to investigate cases of severe
      acute respiratory syndrome (SARS). During November 1, 2002-May 7, 2003, a total
      of 6,903 SARS cases were reported to WHO from 29 countries, including the United
      States; 495 deaths (case-fatality proportion: 7.2%) have been reported. This
      report updates information on reported U.S. SARS cases.

PMID- 12807090
TI  - Nicotine poisoning after ingestion of contaminated ground beef--Michigan, 2003.
AB  - On January 3, 2003, the Michigan Department of Agriculture's (MDA) Food and Dairy
      Division and the U.S. Department of Agriculture (USDA) were notified by a
      supermarket of a planned recall of approximately 1,700 pounds of ground beef
      because of customer complaints of illness after eating the product. On January
      10, the supermarket notified MDA that their laboratory had determined that the
      contaminant in the ground beef returned by customers with reported illness was
      nicotine. This report summarizes the investigation of these cases, which
      identified approximately 100 affected persons, and discusses actions taken to
      prevent additional illness, including the arrest of a person charged with
      deliberately poisoning the ground beef at the supermarket.

PMID- 12807091
TI  - Adults who have never seen a health-care provider for chronic joint symptoms-
      United States, 2001.
AB  - Arthritis and chronic joint symptoms (CJS) are a leading cause of disability
      among adults in the United States. For some forms of arthritis, early diagnosis
      and aggressive treatment are essential to limit permanent joint damage and
      disability. Because CJS can signal inflammatory arthritis, patients with CJS
      should consult a health-care provider to rule out rheumatoid arthritis and other
      forms of inflammatory arthritis. To characterize persons with CJS who do not see
      a health-care provider, CDC analyzed data from the 2001 Behavioral Risk Factor
      Surveillance System (BRFSS). This report summarizes the results of the analysis,
      which indicate that, during 2001, approximately 10.3 million adults (21.7% of
      adults with CJS), including 2.0 million with activity limitations, never had seen
      a health-care provider for their joint symptoms. These persons are missing
      opportunities to limit joint damage and disability and to improve health and
      functional status.

PMID- 12807092
TI  - Update: adverse events following civilian smallpox vaccination--United States,
      2003.
AB  - During January 24-April 25, 2003, smallpox vaccine was administered to 34,541
      civilian health-care and public health workers in 54 jurisdictions to prepare the
      United States for a possible terrorist attack using smallpox virus. This report
      updates information on vaccine-associated adverse events among civilians
      vaccinated since the beginning of the program and among contacts of vaccinees,
      received by CDC from the Vaccine Adverse Event Reporting System (VAERS) as of
      April 25.

PMID- 12807093
TI  - Do Dutch 11-12 years olds who never smoke, smoke experimentally or smoke
      regularly have different demographic backgrounds and perceptions of smoking?
AB  - BACKGROUND: Most adolescent smokers start smoking before the age of twelve.
      Little is known about the behavioural smoking determinants of Dutch primary
      school children. METHODS: A cross-sectional study was carried out on a sample of
      students from the final year of 143 Dutch primary schools. A total of 3700
      students (mean age = 11.6 years) completed a questionnaire based on the ASE
      model, measuring the attitude, social influences and self-efficacy expectations
      concerning smoking. RESULTS: Students were categorized as never smokers (64.3%),
      experimental smokers (28.0%), and regular smokers (7.8%). Multinomial logistic
      regression analyses showed that never smokers were younger, and were more often
      female, religious and from two-parent families than experimental smokers. Never
      smokers perceived more disadvantages, long-term physical consequences, more
      negative social norms and less pressure regarding smoking, higher self-efficacy
      expectations towards non-smoking, and had fewer parents, siblings or best friends
      who smoked. Looking at differences between experimental and regular smokers
      showed that experimental smokers received less pocket money. They also perceived
      more disadvantages, fewer advantages, more negative social norms and less
      pressure towards smoking, higher self-efficacy expectations towards non-smoking,
      and were less likely to be surrounded by friends, peers, family or teachers who
      smoked. Generally, the low scores for physical consequences and risk perception
      regarding addiction were striking. CONCLUSIONS: Smoking prevention aimed at
      primary schoolchildren should consider the different smoking categories, with
      their specific motives and influences. For instance, the influences on smoking
      initiation of parents, siblings and best friends suggest more comprehensive
      programmes aimed at the entire family. Youngsters' ignorance of addiction needs
      more attention.

PMID- 12807094
TI  - [Editorial].

PMID- 12807095
TI  - "Too numerous to count" lesions on magnetic resonance images of the brain.

PMID- 12807096
TI  - The right to health and the nevirapine case in South Africa.

PMID- 12807097
TI  - Advance directives for psychiatric treatment: a view from the trenches.
AB  - Medical advance directives for end-of-life decisions at times that patients
      cannot express their preferences have become a major trend in recent state and
      federal legislation. The author argues that an extension of directives to cover
      future psychiatric treatment are fraught with both practical and ethical
      dilemmas. Although the potential for increasing patient autonomy is certainly
      positive, the potential for implementing covert ideological agendas has been
      present from the beginning, and the significant differences between medical end
      of-life decisions and ongoing treatment of psychiatric patients must weigh
      against psychiatric advance directives unless major changes are made in existing
      procedures.

PMID- 12807098
TI  - Advance directives for psychiatric care: a theoretical and practical overview for
      legal professionals.
AB  - An advance directive for psychiatric care is a legally enforceable document that
      specifies the manner in which psychiatric treatment decisions are to be made in
      the event that a person later becomes incompetent to make informed health care
      decisions. Although the concept of psychiatric advance directives has gained
      considerable popularity in recent years, the groundswell of interest in these
      instruments largely precedes the development of a coherent body of governing law.
      Existing state statutes and case law provide significant legal authority for the
      use and enforcement of advance directives in psychiatric settings, but serious
      questions remain concerning the scope of their enforceability, particularly in
      the context of involuntary treatment.

PMID- 12807099
TI  - Advance directives for mental health care: an analysis of state statutes.
AB  - State statutes enabling individuals to draft written durable advance directives
      for health care have approached future decisions about mental health care and
      treatment in several quite different ways. While some states incorporate mental
      health care into the generic advance directive law, others exclude some kinds of
      mental health care from the generic law, and a growing number of states have
      established distinct processes for mental health directives. The author surveys
      the state statutes and examines the extent to which the statutes may create
      barriers to the use of advance directives by people with mental illness.

PMID- 12807100
TI  - "A place like that": advance directives and nursing home admissions.
AB  - Decisions about admitting a mentally incapacitated person to a nursing home raise
      a variety of difficult legal, ethical, and public policy issues. A strategy for
      anticipating and addressing this contingency prospectively, by encouraging
      execution of formal advance planning directives while the individual is still
      capable, may mitigate some of the dilemmas associated with these issues. The
      author discusses the contours and feasibility of such a strategy, analyzing
      nursing home admission on one's behalf and for refusing such admission, or
      placing explicit conditions on such admission, in advance of the time that the
      actual decision must be made.

PMID- 12807101
TI  - Fou rire prodromique. Case report and systematic review of literature.

PMID- 12807102
TI  - Anticipatory planning for research participants with psychotic disorders like
      schizophrenia.
AB  - Current and coincident biomedical advances make this an opportune time to
      encourage research with individuals who have fluctuating periods of incapacity
      caused by psychotic disorders like schizophrenia. Effecting research with this
      heterogeneous population who may have impaired decision-making capacity that
      diminishes their autonomy, while honoring their liberty and safeguarding their
      well-being, may be difficult to achieve. Federal regulations and guidelines in
      regard to research with this population are insufficient and cause additional
      obstacles. Use of research advance directives that allow for the appointment of a
      surrogate decision maker, the designation of a research monitor, and delineation
      of specific safeguards for the research participants also may provide protection
      for investigators and foster and improve community trust in medical research.

PMID- 12807103
TI  - Cerebral infarction after toluene inhalation.

PMID- 12807104
TI  - Organ donation: a communitarian approach.
AB  - Recently, various suggestions have been made to respond to the increasingly great
      shortage of organs by paying for them. Because of the undesirable side effects of
      such approaches (commodification, injustice, and costs), a communitarian approach
      should be tried first. A communitarian approach to the problem of organ shortage
      entails changing the moral culture so that members of society will recognize that
      donating one's organs, once they are no longer of use to the donor, is the moral
      (right) thing to do. This approach requires much greater and deeper efforts than
      sharing information and making public service announcements. It entails a moral
      dialogue, in which the public is engaged, leading to a change in what people
      expect from one another. Among the devices that could help change the moral
      culture are a public statement, endorsed by community members and leaders, that
      expresses the community sense that donation "is what a good person does" and a
      community-specific web page that lists those who have made the commitment. A
      change in law so that a person's wishes in the matter are recognized as final and
      binding are also desired. This position paper deals only with cadaver organs and
      not living donors.

PMID- 12807105
TI  - Why liberals should accept financial incentives for organ procurement.
AB  - Free market libertarians have long supported incentives to increase organ
      procurement, but those oriented to justice traditionally have opposed them. This
      paper presents the reasons why those worried about justice should reconsider
      financial incentives and tolerate them as a lesser moral evil. After considering
      concerns about discrimination and coercion and setting them aside, it is
      suggested that the real moral concern should be manipulation of the neediest. The
      one offering the incentive (the government) has the resources to eliminate the
      basic needs that pressure the poor into a willingness to sell. It is unethically
      manipulative to withhold those resources and then offer payment for organs.
      Nevertheless, the poor have been left without basic necessities for 20 years
      since the passage of the prohibition on incentives. As long as the government
      continues to withhold a decent minimum of welfare, liberals should, with shame,
      cease opposing financial incentives for organ procurement.

PMID- 12807106
TI  - Operation Blue, ULTRA: DION--the donation inmate organ network.
AB  - Presently more than 80,000 Americans await an organ transplant, while 10 to 12
      people die each day because of the lack of organs. The program proposed here
      would allow federal inmates additional "time off" for agreeing to become living
      donors or to provide organs or their bodies upon death. Such a program could add
      100 to 170 thousand new organ donors to the pool, with another 10 to 12 thousand
      added annually. If the program were applied to all state inmates, up to 4 million
      new donors might be added, with another 10 to 13 thousand added annually. Given
      the extreme need for more organ donors and the need for more living donors, the
      current National Transplant Act of 1984 and the Uniform Anatomical Gift Act must
      be amended, while still retaining control of donation procedures.

PMID- 12807107
TI  - Three views of organ procurement policy: moving ahead or giving up?
AB  - The supply of organs for transplant remains inadequate to meet the needs of
      waiting patients, in spite of many programs and approaches to increase rates of
      donation. Over the years there have been numerous proposals to introduce schemes
      that would move toward the outright sale of organs. Three articles in this issue
      of the Journal propose methods for increasing organ supply--two by moving toward
      a market approach and the third by advocating a change in social culture. All
      three suffer from shortcomings, including the endorsement and encouragement of
      the exploitation of those who may offer organs. Although the shortage of organs
      must be addressed, the social price of a market in organs is too high, and
      proposals to encourage a rethinking of social responsibility are unlikely to be
      effective.

PMID- 12807108
TI  - Congress considers incentives for organ procurement.

PMID- 12807109
TI  - Incentives for providing organs.

PMID- 12807110
TI  - [From gene defect to drug therapy for obesity?].

PMID- 12807111
TI  - [The role of Transylvanian- Saxon Associations in developing health care in the
      period 1880-1944].

PMID- 12807113
TI  - Negligent nurse or scapegoat?

PMID- 12807114
TI  - Iraq's health care system: what now?

PMID- 12807115
TI  - Recent developments in health insurance, life insurance, and disability insurance
      case law.

PMID- 12807116
TI  - Generic drugs.

PMID- 12807117
TI  - ECT controversy.

PMID- 12807118
TI  - ECT controversy.

PMID- 12807119
TI  - ECT controversy.

PMID- 12807120
TI  - User friendly web site a winner. San Diego's Sharp HealthCare provides wealth of
      information.
AB  - The Sharp HealthCare, San Diego, web site, a winner of the 2002 Medicine on the
      Net Web Excellence Award, provides a wealth of information without wasting space
      or confusing the visitor. The web site, www.sharp.com, can be viewed in both
      English and Spanish, a valuable consideration for those living in the California
      Mexico border area served by Sharp. The integrated health network operates seven
      hospitals and three medical group practices. It has 2,541 physicians on medical
      staffs and more than 11,000 employees.

PMID- 12807121
TI  - Hospital ad trends in the spotlight.

PMID- 12807122
TI  - Butylated hydroxytoluene (BHT) at 1000 and 4000 ppm in the diet protected turkeys
      against aflatoxicosis.

PMID- 12807123
TI  - Prescription drug prices in Canada.

PMID- 12807124
TI  - Putting imagery to work for your patient.

PMID- 12807125
TI  - How to ease a patient's anxiety.

PMID- 12807126
TI  - Helping international nurses adjust.

PMID- 12807127
TI  - The cost of contraceptive insurance coverage.

PMID- 12807128
TI  - Lessons from before Roe: will past be prologue?

PMID- 12807129
TI  - Study highlights post-discharge adverse events.

PMID- 12807130
TI  - Study identifies risk factors for women's coronary heart disease.

PMID- 12807131
TI  - Updated colorectal cancer guidelines shift focus from intensive surveillance to
      screening.

PMID- 12807132
TI  - Institute of Medicine committee identifies 20 key areas to transform the U.S.
      health care system.

PMID- 12807133
TI  - Skin protectant drug products for over-the-counter human use; astringent drug
      products; final monograph; direct final rule. Direct final rule.
AB  - The Food and Drug Administration (FDA) is amending the regulation that
      established conditions under which over-the-counter (OTC) skin protectant
      astringent drug products are generally recognized as safe and effective and not
      misbranded. This action revises some labeling for astringent drug products to be
      consistent with the final rule for OTC skin protectant drug products (68 FR
      33362, June 4, 2003) and adds labeling for certain small packages (styptic
      pencils). This action is part of FDA's ongoing review of OTC drug products.
      Elsewhere in this issue of the Federal Register, FDA is publishing a companion
      proposed rule, under FDA's usual procedure for notice-and-comment rulemaking, to
      provide a procedural framework to finalize the rule in the event the agency
      receives any significant adverse comments and withdraws this direct final rule.

PMID- 12807135
TI  - Tracking health care costs: trends stabilize but remain high in 2002.

PMID- 12807134
TI  - ViewPoint--human or interpersonal side of research. Interview by David R. Black
      and Molly T. Laflin.

PMID- 12807136
TI  - Storage temperature affects the quality of cut flowers from the Asteraceae.
AB  - The respiration of cut flowers of gerbera (Gerbera jamesonii H. Bolus ex Hook.f.
      'Vesuvio') and sunflower (Helianthus annuus L.) increased exponentially with
      increasing storage temperature. Poststorage vase life and negatively gravitropic
      bending of the neck of the flowers were both strongly affected by simulated
      transport at higher temperatures. Vase life and stem bending after dry storage
      showed highly significant linear relationships (negative and positive,
      respectively) with the rate of respiration during storage. The data indicate the
      importance of maintaining temperatures close to the freezing point during
      commercial handling and transport of these important commercial cut-flower crops
      for maximum vase life.

PMID- 12807137
TI  - Functional development of small intestine of Japanese quail hatched on MIR
      orbital station.
AB  - The effect of microgravity on functional development of the small intestine of
      Japanese quails incubated for 2-3 d and hatched on the orbital station MIR was
      examined. After 5 d of space flight duodenal and jejunal alkaline phosphatase
      (AP) activity of the experimental group was compared with the AP activity in
      quails of the same age hatched on the Earth (laboratory controls). Short-term
      microgravity leading to decreased food intake resulted in significant increase of
      AP activity in both duodenal and jejunal enterocytes (P<0.001) of the
      experimental quails. The results suggest that increased AP activity probably
      reflects the delayed functional development of the small intestine as a
      consequence of inappropriate food intake during non-physiological conditions of
      space flight.

PMID- 12807138
TI  - The TERESA project: from space research to ground tele-echography.
AB  - Ultrasound examinations represent one of the major diagnostic modalities of
      future healthcare. They are currently used to support medical space research but
      require a high skilled operator for both probe positioning on the patient's skin
      and image interpretation. TERESA is a tele-echography project that proposes a
      solution to bring astronauts and remotely located patients on ground quality
      ultrasound examinations despite the lack of a specialist at the location of the
      wanted medical act.

PMID- 12807139
TI  - Diffusion NMR methods applied to xenon gas for materials study.
AB  - We report initial NMR studies of (i) xenon gas diffusion in model heterogeneous
      porous media and (ii) continuous flow laser-polarized xenon gas. Both areas
      utilize the pulsed gradient spin-echo (PGSE) techniques in the gas phase, with
      the aim of obtaining more sophisticated information than just translational self
      diffusion coefficients--a brief overview of this area is provided in the
      Introduction. The heterogeneous or multiple-length scale model porous media
      consisted of random packs of mixed glass beads of two different sizes. We focus
      on observing the approach of the time-dependent gas diffusion coefficient, D(t)
      (an indicator of mean squared displacement), to the long-time asymptote, with the
      aim of understanding the long-length scale structural information that may be
      derived from a heterogeneous porous system. We find that D(t) of imbibed xenon
      gas at short diffusion times is similar for the mixed bead pack and a pack of the
      smaller sized beads alone, hence reflecting the pore surface area to volume ratio
      of the smaller bead sample. The approach of D(t) to the long-time limit follows
      that of a pack of the larger sized beads alone, although the limiting D(t) for
      the mixed bead pack is lower, reflecting the lower porosity of the sample
      compared to that of a pack of mono-sized glass beads. The Pade approximation is
      used to interpolate D(t) data between the short- and long-time limits. Initial
      studies of continuous flow laser-polarized xenon gas demonstrate velocity
      sensitive imaging of much higher flows than can generally be obtained with
      liquids (20-200 mm s-1). Gas velocity imaging is, however, found to be limited to
      a resolution of about 1 mm s-1 owing to the high diffusivity of gases compared
      with liquids. We also present the first gas-phase NMR scattering, or diffusive
      diffraction, data, namely flow-enhanced structural features in the echo
      attenuation data from laser-polarized xenon flowing through a 2 mm glass bead
      pack.

PMID- 12807141
TI  - The role of cross-cultural factors in long-duration international space missions:
      lessons from the SFINCSS-99 study.
AB  - The role of cross-cultural factors in long-duration international space missions
      was examined during an isolation study that simulated many of the conditions
      aboard the International Space Station. METHODS: Interactions involving two
      heterogeneous crews and one homogeneous crew staying in isolation from 110 to 240
      days were studied. Data consisted of post-isolation interviews with crewmembers,
      ground support personnel and management, observational data, and public
      statements by crewmembers. Data was analyzed using the techniques of linguistic
      anthropology and ethnography. RESULTS: Sub-cultural (organizational and
      professional) differences played a larger role than national differences in
      causing misunderstandings in this study. Conversely, some misunderstandings and
      conflicts were escalated by participants falsely assuming cultural differences or
      similarities. Comparison between the two heterogeneous crews showed the
      importance of training, personality factors, and commander and language skills in
      preventing and alleviating cultural misunderstandings. CONCLUSION: The study
      revealed a number of ways that cultural differences, real as well as assumed, can
      play a role and interact with other, non-cultural, factors in causing and/or
      precipitating conflict situations. It is postulated that such difficulties can be
      avoided by selecting culturally adaptive crewmembers and by cross-cultural and
      language training. Also the crew composition and role of commander were found to
      be important in mitigating conflict situations.

PMID- 12807140
TI  - Evaluation of two fiber optic-based solar collection and distribution systems for
      advanced space life support.
AB  - Growing plants in an enclosed controlled environment is crucial in developing
      bioregenerative life-support systems (BLSS) for space applications. The major
      challenge currently facing a BLSS is the extensive use of highly energy-intensive
      electric light sources, which leads to substantial energy wastes through heat
      dissipations by these lamps. An alternative lighting strategy is the use of a
      solar irradiance collection, transmission, and distribution system (SICTDS). Two
      types of fiber optic-based SICTDS, a Fresnel-lens Himawari and a parabolic-mirror
      optical waveguide (OW) lighting system, were evaluated. The overall efficiency
      for the OW SICTDS of 40.5% exceeded by 75% that for the Himawari of 23.2%. The
      spectral distributions of the light delivered by the Himawari and the OW SICTDS
      were almost identical and had practically no difference from that of terrestrial
      solar radiation. The ratios of photosynthetically active radiation (PAR) to total
      emitted radiation (k) of 0.39 +/- 0.02 for the Himawari and 0.41 +/- 0.04 for the
      OW SICTDS were statistically indistinguishable, were not significantly different
      from that of 0.042 +/- 0.01 for terrestrial solar radiation, and were comparable
      to that of 0.35 for a high-pressure sodium (HPS) lamp. The coefficients of
      variation (CV) of 0.34 and 0.39 for PPF distributions, both at 50 mm X 50 mm
      square grid arrays, corresponding to the Himawari and the OW SICTDS,
      respectively, were comparable with each other but were both significantly greater
      than the CV of 0.08 corresponding to the HPS lamp. The average fresh weight or
      dry weight of lettuce grown in the solar chamber with either the Himawari or the
      OW SICTDS showed no statistical difference from the average fresh weight or dry
      weight of lettuce grown in the reference chamber with the HPS lamp. The results
      of this study suggest that an SICTDS could help reduce the electric power demand
      in a BLSS.

PMID- 12807142
TI  - [A survey of the studies on chemical constituents and pharmacological activities
      of Acorus plants].

PMID- 12807143
TI  - Immunoaffinity beads for selective removal of cholesterol from human plasma.
AB  - Anti-low density lipoprotein antibody (anti-LDL antibody) attached poly(2
      hydroxyethyl methacrylate-methacryloylamidophenylalanine) (poly(HEMA-MAPA)) beads
      were prepared for selective removal of cholesterol from hypercholesterolemic
      human plasma. Poly(HEMA-MAPA) beads were produced by a modified suspension
      polymerization and then characterized by swelling tests and SEM. Blood
      compatibility tests were also investigated. The water swelling ratio of the
      poly(HEMA-MAPA) beads increased significantly (68%) compared with pHEMA (55%).
      All the clotting times increased when compared with poly(HEMA) beads. Loss of
      platelets and leukocytes was very low. The maximum anti-LDL antibody attachment
      was achieved at pH 7.0. Attachment of anti-LDL antibody was 29.6 mg/g. There was
      a very low non-specific cholesterol binding onto the poly(HEMA-MAPA) beads, about
      0.74 mg/g. Anti-LDL antibody attached beads adsorbed in the range of 13.3-16.0 mg
      cholesterol/g from hypercholesterolemic human plasma. Up to 92% of the adsorbed
      LDL was desorbed. The binding-elution cycle was repeated 10 times using the same
      beads. There was no significant loss of binding capacity.

PMID- 12807144
TI  - Covalent immobilization of O-butyrylchitosan with a photosensitive hetero
      bifunctional crosslinking reagent on biopolymer substrate surface and
      bloodcompatibility characterization.
AB  - O-Butyrylchitosan (OCS) was covalently immobilized onto a substrate (suture and
      PTFE) surface using the photosensitive hetero-bifunctional crosslinking reagent 4
      azidobenzoic acid, which was previously bonded to OCS by the reaction between an
      acid group of the crosslinking reagent and a free amino group of OCS. The
      immobilization was accomplished by irradiating the modified OCS coated on the
      substrate surface with ultraviolet light to photolyze azide groups, thus the
      crosslinking OCS was immobilized on the substrate surface. The result indicated
      that OCS molecules immobilized on the substrate, and significantly reduced the
      fibrinogen adsorption and the deposition and spreading of platelets,
      demonstrating superior bloodcompatibility. Therefore, OCS could be developed into
      bloodcompatible biomaterial that used to modify the biomedical devices, such as
      PTFE and Dacron vascular prostheses surface.

PMID- 12807145
TI  - Chitosan: potential use as a bioactive coating for orthopaedic and
      craniofacial/dental implants.
AB  - Chitosan is a biopolymer that exhibits osteoconductive, enhanced wound healing
      and antimicrobial properties which make it attractive for use as a bioactive
      coating to improve osseointegration of orthopaedic and craniofacial implant
      devices. Coatings made from 91.2% de-acetylated chitosan were chemically bonded
      to titanium coupons via silane-glutaraldehyde molecules. The bond strength of the
      coatings was evaluated in mechanical tensile tests, and their dissolution and
      cytocompatibility were evaluated in vitro using cell-culture medium and UMR 106
      osteoblastic cells, respectively. The results showed that the chitosan coatings
      were chemically bonded to the titanium substrate and that the bond strengths (1.5
      1.8 MPa) were not affected by gas sterilization. However, the chitosan bond
      strengths were less than those reported for calcium-phosphate coatings. The gas
      sterilized coatings exhibited little dissolution over 8 weeks in cell-culture
      solution, and the attachment and growth of the UMR 106 osteoblast cells was
      greater on the chitosan-coated samples than on the uncoated titanium. These
      results indicated that chitosan has the potential to be used as a biocompatible,
      bioactive coating for orthopaedic and craniofacial implant devices.

PMID- 12807146
TI  - Albumin and fibrinogen adsorption on cibacron blue F3G-A immobilised onto PU
      PHEMA (polyurethane-poly(hydroxyethylmethacrylate)) surfaces.
AB  - In the present work, it is intended to study the effect of Cibacron blue F3G-A
      (CB) immobilised onto PU-PHEMA (polyurethane-poly(hydroxyethylmethacrylate))
      surfaces on protein adsorption and bacterial adhesion. CB immobilisation was
      carried out by covalent binding between its triazine ring and the hydroxyl groups
      of the polymer. Characterisation of the films was carried out by attenuated total
      reflection Fourier transform infrared spectroscopy (ATR-FT-IR), contact angle
      measurements. X-ray photoelectron spectroscopy (XPS) and scanning electron
      microscopy (SEM). CB efficiency was evaluated using radiolabelled albumin and
      fibrinogen from pure solutions, mixtures of both and plasma. Bacterial adhesion
      tests before and after albumin pre-coating were also performed. The presence of
      CB increases albumin and fibrinogen adsorption to PU-PHEMA surfaces. The
      incorporation of CB onto the PU-PHEMA surface also increases bacterial adhesion.
      Although albumin pre-coating decreases bacterial adhesion onto PU (67% decrease)
      and PU-PHEMA-CB (80%), bacterial adhesion is always lower on PU and PU-PHEMA
      surfaces than on PU-PHEMA-CB. These results demonstrate that, in contrast to what
      has been described for CB bound to dextran, CB immobilisation on PU-PHEMA
      surfaces presents low selectivity to albumin and increased bacterial adhesion
      relatively to PU and PU-PHEMA surfaces.

PMID- 12807147
TI  - Graft polymerization of glycidylmethacrylate onto coralline hydroxyapatite.
AB  - Graft polymerization of glycidylmethacrylate (GMA) onto coralline hydroxyapatite
      (CHA) was carried out using potassium persulfate (K2S2O8) and sodium
      metabisulfite (Na2S2O5) as initiators in aqueous medium. To optimize the reaction
      conditions for getting maximum grafting yield, the concentrations of backbone,
      monomer, initiator, temperature and time were varied. The percent grafting was
      found to increase initially and then gradually decrease with respect to reaction
      parameters. The results obtained imply that the optimum temperature and time was
      60 degrees C and 180 min, respectively, to obtain higher grafting yield. The
      grafting results have been discussed and a mechanism involved in the grafting of
      GMA onto CHA is described. The grafted materials were analyzed with Fourier
      transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) measurements.
      The results of FT-IR confirmed the presence of epoxy group on the grafted CHA.
      The XRD pattern showed that there was no secondary phase in the apatite lattice
      due to chemical modification.

PMID- 12807148
TI  - Biocompatibility of fluorinated poly(organophosphazene).
AB  - We investigated neutrophil and platelet adhesion on a fluorinated
      poly(organophosphazene) in vitro. The results suggested that neutrophil and
      platelet adhesion on the poly(organophosphazene) only occurred on a few
      occasions, as observed by SEM. We demonstrated that the fluorinated
      poly(organophosphazene) showed excellent biocompatibility compared with the
      poly(organophosphazene) without the fluorinated side groups or PDMS.
      Additionally, we estimated the competitive plasma protein adsorption to the
      fluorinated poly(organophosphazene) using a gold-colloid-labeled immunoassay.
      Interestingly, the fluorinated poly(organophosphazene) film selectively adsorbed
      albumin when compared with gamma-globulin and fibrinogen, suggesting that a
      selective albumin adsorption on the film is responsible for the suppression of
      platelet adhesion.

PMID- 12807149
TI  - A genipin-crosslinked gelatin membrane as wound-dressing material: in vitro and
      in vivo studies.
AB  - A naturally occurring crosslinking agent (genipin) was used in this study to
      crosslink gelatin hydrogel to develop a wound-dressing membrane. The study was to
      investigate the in vitro characteristics of the genipin-crosslinked gelatin
      membrane. The glutaraldehyde-crosslinked counterpart, at a similar crosslinking
      degree, was used as control. Additionally, an in vivo experiment was undertaken
      to study the wound healings covered with the glutaraldehyde- and genipin
      crosslinked dressings in a rat model. The in vitro results obtained suggested
      that crosslinking of gelatin membranes with glutaraldehyde or genipin may produce
      distinct crosslinking structures. The differences in crosslinking structure can
      significantly affect the mechanical property, water-vapor-transmission rate,
      swelling ratio, degradation against enzyme and cellular compatibility of the
      crosslinked membranes. In the in vivo study, it was found that the degree of
      inflammatory reaction for the wound treated with the genipin-crosslinked dressing
      was significantly less severe than that covered with the glutaraldehyde
      crosslinked dressing throughout the entire course of the study. Additionally, the
      healing rate for the wound treated with the genipin-crosslinked dressing was
      notably faster than its glutaraldehyde-crosslinked counterpart.

PMID- 12807150
TI  - Sarcoidosis: global scenario & Indian perspective.
AB  - Sarcoidosis is now recognised as a member of a large family of granulomatous
      disorders and has been reported from all parts of the world. Current evidence
      points to genetic predisposition and exposure to yet unknown transmissible
      agent(s) and/or environmental factors as etiological agents. Depending on the
      organ systems involved, patients with sarcoidosis present themselves to various
      specialities; pulmonary involvement is by far the commonest and occurs in about
      90 per cent of the patients. The diagnosis is based on a compatible clinical
      and/or radiological picture, histopathological evidence of non-caseating
      granulomas in tissue biopsy specimens and exclusion of other diseases capable of
      producing similar clinical or histopathological appearances. Sarcoidosis is an
      underdiagnosed disease in India. However, owing to the increasing awareness, it
      is being diagnosed more frequently than a few decades ago. Most Indian patients
      with sarcoidosis are males and present in the fourth or fifth decade of life. The
      disease runs a benign course with spontaneous remission of the activity though
      some degree of residual pulmonary function abnormality persists. Only a minority
      of the patients develop complicated disease. Corticosteroids remain the mainstay
      of treatment. For asymptomatic patients with pulmonary sarcoidosis, no therapy is
      required. Corticosteroid treatment should be considered in symptomatic patients
      with evidence of radiological or pulmonary function deterioration. Treatment
      under close clinical monitoring should be tailored to suit the needs of the
      individual patient. Sometimes steroid-sparing alternative treatments may be
      beneficial. In this review, the current understanding of the global scenario and
      Indian perspective of sarcoidosis are critically reviewed.

PMID- 12807151
TI  - Serological & virological investigation of an outbreak of dengue fever in
      Gwalior, India.
AB  - BACKGROUND & OBJECTIVES: An outbreak of febrile illness occurred between
      September to November 2001 in Gwalior, Madhya Pradesh affecting individuals
      mostly in the age group < 30 yr. A total of 312 febrile indoor patients suspected
      to have dengue infection were investigated. METHODS: The investigation included
      examination of blood samples from patients for dengue specific IgM and IgG
      antibodies, isolation of virus in suckling mouse pups and in C(6/36) cell line
      followed by confirmation and typing through reverse transcriptase-PCR and nested
      PCR. RESULTS: The serological analysis of the 312 samples indicated 65 per cent
      positivity of which 21 per cent are of recent infection as indicated by the
      presence of IgM antibody and 78 per cent are found to be secondary in nature by
      showing the presence of IgG and/or IgM antibodies. The RT-PCR analysis of
      patients' sera employing dengue virus group specific conserved amplimer confirmed
      the etiological agent as dengue complex by showing the characteristic 511 bp
      amplicons. None of the antibody positive samples were found to be positive by RT
      PCR. A total of 13 (6%) samples positive by RT-PCR, were processed for virus
      isolation in mouse pups and in C(6/36) cells. Of these 9 samples (80%) were
      confirmed positive for virus isolation as identified by RT-PCR. INTERPRETATION &
      CONCLUSION: The typing of isolates by nested PCR employing serotype specific
      amplimer revealed 119 bp amplicon characteristic of dengue virus type-2 and thus
      confirming the outbreak attributed to dengue virus type-2.

PMID- 12807152
TI  - Growth of respiratory syncytial virus in mink lung epithelial cells.
AB  - Mink lung epithelial cells (Mv-1-Lu) were tested for their ability to support the
      growth and serial passage of respiratory syncytial virus (RSV) in vitro. Indian
      isolates of RSV induced distinctive cytopathic effect with typical rounding of
      cells followed by detachment with more than 50 per cent cells showing bright
      fluorescence using anti-RSV monoclonal antibodies in immunofluorescence test.
      Serial passage of RSV was possible in Mv-1-Lu cells without loss of sensitivity
      of the cells for virus growth. Titration of cell associated virus and virus
      released in the supernatant indicated that 60 per cent of the virus was released
      in the supernatant, and 40 per cent remained cell associated. Transmission
      electron microscopic studies of negatively stained RSV particles and ultra-thin
      sections of RSV infected Mv-1-Lu cells showed roughly spherical particles with
      club shaped projections, budding from the cytoplasmic membrane. These results
      indicate that Mv-1-Lu cell line is suitable for the growth and propagation of
      RSV.

PMID- 12807153
TI  - Bacteriological profile of cholera in Tamil Nadu (1980-2001).
AB  - BACKGROUND & OBJECTIVE: In addition to Vibrio cholerae O1, a recently emerged non
      O1 serotype, V. cholerae O139 has also been found to be responsible for epidemics
      of cholera. In the context of the changing etiology of cholera, the occurrence of
      different serotypes, biotypes and phage types of V. cholerae in Tamil Nadu is
      presented. METHODS: Between 1980 and 2001, 26,502 stool/rectal swabs from
      patients suspected to have cholera were processed for the presence of V. cholerae
      at the King Institute of Preventive Medicine, Chennai (Madras), Tamil Nadu.
      Serotypes, biotypes and phage types (Basu & Mukerjee and new phage typing method)
      of the isolates were determined. Antimicrobial susceptibility determination was
      included from 1997 onwards. RESULTS: Of the 26,502 stool/rectal swabs tested,
      6035 (22.8%) specimens yielded V. cholerae. 4,046 (67%) of them were O1 serotype;
      followed by 1529 (25.3%) O139 serotype and 448 (7.4%) non-O1 serotypes other than
      O139 were encountered. Twelve specimens yielded rough strains of V. cholerae. All
      V. cholerae O1 were the biotype ElTor and the predominant serotype was Ogawa
      (95.9%). After the initial explosive epidemic by O139 serotype in late 1992 and
      early 1993 occurrence of this serotype had declined. Resurgence of this new
      serotype was observed in 1997. O1 domination was observed during 1995 and 1996.
      The new phage typing scheme for V. cholerae O1 was able to differentiate the
      isolates into 22 types, type 27 (68.2%) being the predominant one followed by
      type 26 (12.3%). In Basu & Mukerjee scheme, the isolates were clustered between
      two types--type 2 (34%) and type 4 (61%). Further, about 5 per cent of them were
      untypeable. All but a few of the isolates irrespective of serotype, were
      susceptible to chloramphenicol, tetracycline, gentamicin and ciprofloxacin. 97
      per cent of the O1 strains and 48.9 per cent of the O139 strains were resistant
      to cotrimoxazole. INTERPRETATION & CONCLUSION: V. cholerae O139 might have the
      ability to survive during interepidemic periods. Both V. cholerae O1 and O139-
      the two serotypes with epidemic potential seem to be firmly established in this
      region. This situation warrants constant surveillance.

PMID- 12807154
TI  - A preliminary study on metallo-beta-lactamase producing Pseudomonas aeruginosa in
      hospitalized patients.
AB  - Metallo beta-lactamase (MBL) producing Pseudomonas aeruginosa is an emerging
      threat and a cause of concern for the physicians treating such infections. The
      present study was undertaken to know the resistance pattern of P. aeruginosa to
      beta-lactamase inhibitors and carbapenems, and to detect the presence of MBL
      among resistant isolates to both groups of antibiotics. Between June-November
      2001, 50 P. aeruginosa isolates from clinical specimens were tested for
      susceptibility to beta-lactamase inhibitors and carbapenems by Kirby-Bauer disc
      diffusion method. Isolates resistant to both groups of antibiotics were screened
      for the presence of MBLs by disc diffusion method using 2-mercaptoethanol. Of the
      50 isolates, 6 (12%) were resistant to both beta-lactamase inhibitors and
      carbapenems. All 6 isolates were MBL producers were resistant to all the
      antibiotics tested. Resistance to piperacillin-tazobactam, cefoperazone-sulbactam
      and ticarcillin-clavulanic acid was 12, 20 and 36 per cent respectively.
      Resistance of 12 per cent each was noted to imipenem and meropenem respectively.
      This is to the best of our knowledge the first report of MBL producing P.
      aeruginosa from India and suggests the need for early detection, notification and
      control of spread.

PMID- 12807155
TI  - In vitro resistance of leukaemic blasts to prednisolone in bcr-abl positive
      childhood acute lymphoblastic leukaemia.
AB  - BACKGROUND & OBJECTIVES: Although the outcome of children with acute
      lymphoblastic leukaemia (ALL) has improved dramatically over the last decade,
      some children still fare poorly and relapses are seen. The sensitivity of
      leukaemic cells to corticosteroids has emerged as an important prognostic factor
      in ALL. The t(9,22) translocation, resulting in the bcr-abl fusion gene, is a non
      random translocation found in B-lineage acute lymphoblastic leukaemia. It is also
      known to be an independent poor prognostic factor for long-term disease free
      survival. We studied the association between the presence of bcr-abl fusion gene
      and in vitro prednisolone resistance in children with B-lineage acute
      lymphoblastic leukaemia at diagnosis. METHODS: A total of 23 children (aged 1-16
      yr, median age: 12 yr) with B-lineage acute lymphoblastic leukaemia at diagnosis
      were included in the study. The presence of bcr-abl fusion gene was determined by
      reverse transcriptase-polymerase chain reaction (RT-PCR) and the in-vitro
      resistance to prednisolone was measured by short term colorimetric methyl thiazol
      tetrazolium (MTT) assay. RESULTS: A median LD50 (lethal dose for 50% cells) for
      prednisolone in bcr-abl positive children (n=7) was 1.6 mg/ml (range: 0.25-5.0
      mg/ml) and that of bcr-abl negative children (n=16) was 0.35 mg/ml (range 0.62
      1.0 mg/ml). The median LD50 for prednisolone differed significantly between the
      bcr-abl positive and negative groups of children with acute lymphoblastic
      leukaemia (P<0.005). INTERPRETATION & CONCLUSION: This is probably the first
      report to show that leukaemic blasts of bcr-abl positive children with ALL are
      about four-fold resistant to prednisolone as compared to blasts from bcr-abl
      negative children. This suggests that one of the reasons for the poor prognosis
      of bcr-abl positive ALL could be a lower steroid sensitivity.

PMID- 12807156
TI  - In vitro analysis of the wear, wear debris and biological activity of surface
      engineered coatings for use in metal-on-metal total hip replacements.
AB  - Extremely low wear rates have been reported for metal-on-metal total hip
      replacements, but concerns remain about the effects of metal ion release,
      dissolution rates and toxicity. Surface-engineered coatings have the potential to
      improve wear resistance and reduce the biological activity of the wear debris
      produced. The aim of this study was to examine the wear and wear debris
      generation from surface-engineered coatings: titanium nitride (TiN), chromium
      nitride (CrN) and chromium carbon nitride (CrCN) applied to a cobalt-chrome alloy
      (CoCr) substrate. The coatings were articulated against themselves in a simple
      geometry model. The wear particles generated were characterized and the cytotoxic
      effect on U937 macrophages and L929 fibroblasts assessed. The CrN and CrCN
      coatings showed a decrease in wear compared to the CoCr bearings and produced
      small (less than 40 nm in length) wear particles. The wear particles released
      from the surface engineered bearings also showed a decreased cytotoxic effect on
      cells compared to the CoCr alloy debris. The reduced wear volumes coupled with
      the reduced cytotoxicity per unit volume of wear indicate the potential for the
      clinical application of this technology.

PMID- 12807157
TI  - Development and numerical validation of a finite element model of the muscle
      standardized femur.
AB  - The human femur is one of the parts of the musculo-skeletal system most
      frequently analysed by means of the finite element (FE) method. Most FE studies
      of the human femur are based on computed tomography data sets of a particular
      femur. Since the geometry of the chosen sample anatomy influences the computed
      results, direct comparison across various models is often difficult or
      impossible. The aim of the present work was to develop and validate a novel three
      dimensional FE model of the human femur based on the muscle standardized femur
      (MuscleSF) geometry. In the new MuscleSF FE model, the femoral attachment of each
      muscle was meshed separately on the external bone surface. The model was tested
      under simple load configurations and the results showed good agreement with the
      converged solution of a former study. In the future, using the validated MuscleSF
      FE model for numerical studies of the human femur will provide the following
      benefits: (a) the numerical accuracy of the model is known; (b) muscle attachment
      areas are incorporated in the model, therefore physiological loading conditions
      can be easily defined; (c) analyses of the femur under physiological load cases
      will be replicable; (d) results based on different load configurations could be
      compared across various studies.

PMID- 12807158
TI  - Strain distribution within the human femur due to physiological and simplified
      loading: finite element analysis using the muscle standardized femur model.
AB  - The aim of the current work was to study the effect of simplified loading on
      strain distribution within the intact femur using the Muscle Standardized Femur
      finite element model and to investigate whether the interaction between the
      intact human femur and the muscles which are attached to the bone surface could
      accurately be represented by concentrated forces, applied through the centroids
      of their attachment areas. An instant at 10 per cent of the gait cycle during
      level walking was selected as the reference physiological load case; nine load
      cases were analysed. Comparison of the calculated results for the physiological
      load case with muscle forces uniformly distributed over their attachment areas
      showed good agreement with in vivo measurements of strain values and femoral head
      displacement in humans. Simplified load cases generated unrealistic displacement
      results and high strain magnitudes, exceeding the physiological range. It was
      found that when muscles with large attachment areas are included in the model and
      the muscle forces are simplified, stress and strain distributions will be
      affected not only on the external bone surface in the vicinity of the load
      application node, but also on the internal surface of the cortical bone. However,
      applying muscle forces as concentrated loads at the centroids of the attachment
      areas can serve as first indicators of the physiological stress and strain
      levels, if results from nodes and elements in the vicinity of the load
      application nodes are discarded. Omitting muscle forces or fixing the femur in
      mid-shaft leads to large unphysiological strain values.

PMID- 12807160
TI  - The influence of stem insertion rate on the porosity of the cement mantle of hip
      joint replacements.
AB  - This study investigates the effect of stem insertion rate on the porosity of the
      cement mantle. An experimental protocol was developed to simulate the surgical
      technique of cementing a prosthetic stem into the medullary canal of the femur.
      Cement mantle specimens were produced for three different stem insertion rates.
      The presence of porosity in the cement mantle was investigated. Additionally, the
      mechanical strength of the bone cement was assessed. Increasing the stem
      insertion rate did not have a significant effect on the porosity distribution
      within the bulk cement mantle. However, for all stem insertion rates
      investigated, the porosity concentration increased significantly moving from the
      cement/pseudofemur interface through to the stem/cement interface. In all cases,
      the presence of porosity significantly decreased the mechanical behaviour of the
      bone cement. High porosity concentration at the stem/cement interface seems to be
      attributed also to the rheology of the cement during implant insertion.
      Nevertheless, the surgeon cannot influence the formation of porosity by changing
      the stem insertion rate.

PMID- 12807159
TI  - Elastohydrodynamic lubrication analysis of a functionally graded layered bearing
      surface, with particular reference to 'cushion form bearings' for artificial knee
      joints.
AB  - Elastohydrodynamic lubrication of a functionally graded layered (FGL) bearing
      surface, whose elastic modulus increases with depth from the bearing surface, was
      investigated in this study. The finite difference method was employed to solve
      the Reynolds equation, simultaneously with the elasticity equation of the bearing
      surface, under circular point contacts. The finite element method was adopted to
      solve the elasticity equation for the FGL bearing surface. The displacement
      coefficients thus obtained were used to calculate the elastic deformation of the
      bearing surface, required for the elastohydrodynamic lubrication analysis. Good
      agreement of the predicted film thickness and pressure distribution was obtained,
      between the present method and a previous study for a single layered bearing
      surface with a uniform elastic modulus. The general numerical methodology was
      then applied to an FGL bearing surface with both linear and exponential
      variations in elastic modulus, with particular reference to the 'cushion form
      bearing' for artificial knee joints. The predicted film thickness and pressure
      distribution were shown to be quite close to those obtained for a single layer
      under typical operating conditions representative of artificial knee joints,
      provided that the elastic modulus of the single layer was chosen to be the
      average elastic modulus of the graded layer.

PMID- 12807162
TI  - Mechanical anisotropy of the human knee articular cartilage in compression.
AB  - Articular cartilage exhibits anisotropic mechanical properties when subjected to
      tension. However, mechanical anisotropy of mature cartilage in compression is
      poorly known. In this study, both confined and unconfined compression tests of
      cylindrical cartilage discs, taken from the adult human patello-femoral groove
      and cut either perpendicular (normal disc) or parallel (tangential disc) to the
      articular surface, were utilized to determine possible anisotropy in Young's
      modulus, E, aggregate modulus, Ha, Poisson's ratio, v and hydraulic permeability,
      k, of articular cartilage. The results indicated that Ha was significantly higher
      in the direction parallel to the articular surface as compared with the direction
      perpendicular to the surface (Ha = 1.237 +/- 0.486 MPa versus Ha = 0.845 +/-
      0.383 MPa, p = 0.017, n = 10). The values of Poisson's ratio were similar, 0.158
      +/- 0.148 for normal discs compared with 0.180 +/- 0.046 for tangential discs.
      Analysis using the linear biphasic model revealed that the decrease of
      permeability during the offset compression of 0-20 per cent was higher (p =
      0.015, n = 10) in normal (from 25.5 x 10(-15) to 1.8 x 10(-15) m4/N s) than in
      tangential (from 12.3 x 10(-15) to 1.3 x 10(-15) m4/N s) discs. Based on the
      results, it is concluded that the mechanical characteristics of adult femoral
      groove articular cartilage are anisotropic also during compression. Anisotropy
      during compression may be essential for normal cartilage function. This property
      has to be considered when developing advanced theoretical models for cartilage
      biomechanics.

PMID- 12807161
TI  - Contact mechanics of metal-on-metal hip implants employing a metallic cup with a
      UHMWPE backing.
AB  - The contact mechanics in metal-on-metal hip implants employing a cobalt chromium
      acetabular cup with an ultra-high molecular weight polyethylene (UHMWPE) backing
      were analysed in the present study using the finite element method. A general
      modelling methodology was developed to examine the effects of the interfacial
      boundary conditions between the UHMWPE backing and a titanium shell for
      cementless fixation, the coefficient of friction and the loading angle on the
      predicted contact pressure distribution at the articulating surfaces. It was
      found that the contact mechanics at the bearing surfaces were significantly
      affected by the UHMWPE backing. Consequently, a relatively constant pressure
      distribution was predicted within the contact conjunction, and the maximum
      contact pressure occurred towards the edge of the contact. On the other hand, the
      interfacial boundary condition between the UHMWPE backing and the titanium shell,
      the coefficient of friction and the loading angle were found to have a negligible
      effect on the contact mechanics at the bearing surfaces. Overall, the magnitude
      of the contact pressure was significantly reduced, compared with a similar cup
      without the UHMWPE backing. The importance of the UHMWPE backing on the
      tribological performance of metal-on-metal hip implants is discussed.

PMID- 12807163
TI  - Fatigue strength of a wire passing through a cannulated screw: implications for
      closure of the sternum following cardiac surgery.
AB  - It has been proposed that the incidence of sternal dehiscence can be decreased by
      passing the wires used for sternotomy closure through cannulated screws. However,
      there is a potential risk of fatigue failure as a result of the wire moving
      against the screw, e.g. during coughing and sneezing. The system of cannulated
      screws and wire was subjected to static tensile testing to failure. Five tests
      were performed and failure occurred at 388 +/- 34 N (mean +/- SD). Ten cyclic
      tests were then performed. Sinusoidal loading was applied at 10 Hz with peak
      forces in the range 10-90 per cent of the static failure force, at a constant
      load ratio R = 10. The test with the lowest peak force reached run-out at 6 x
      10(6) cycles. The others failed by the ends of the wire closures becoming
      untwisted (one test), the wire fracturing at the twist (three tests) or the wire
      fracturing at the screw (five tests). However, calculations based on these
      results suggest that fatigue failure is unlikely to occur as a result of regular
      breathing or continuous coughing or sneezing.

PMID- 12807165
TI  - Efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler) during
      52 weeks of treatment in adults and children with persistent asthma.
AB  - BACKGROUND: Inhaled corticosteroids are the agents of choice for treating
      persistent asthma. OBJECTIVE: To evaluate the long-term efficacy and safety of
      budesonide inhalation powder (Pulmicort Turbuhaler) in patients with mild to
      severe persistent asthma. METHODS: Patients (n=1133) received open-label
      budesonide (dose range, 100-800 microg b.i.d.) for 52 weeks following 2 weeks to
      5 months of treatment in one of four double-blind, placebo-controlled studies.
      Patients, identified before the double-blind studies, included adults (n=249) not
      receiving corticosteroids, adults (n=384) and children (n=356) previously
      maintained on inhaled corticosteroids, and adults (n=144) previously maintained
      on oral corticosteroids. RESULTS: Mean forced expiratory volume in 1 sec was
      68.2% of predicted normal (n=1133) at baseline (mean from two visits before
      randomization), 74.4% (n=1132) at the end of double-blind treatment, 81.3%
      (n=971) at week 52, and 80.1% (n=1125) at last observation (including patients
      who discontinued early). Sixty-four patients maintained on oral corticosteroids
      before double-blind treatment entered the open-label study off oral
      corticosteroids, 58 of whom (91%) remained oral corticosteroid-free throughout
      the study. There was no evidence of basal or cosyntropin-stimulated hypothalamic
      pituitary-adrenal axis function suppression, and the most commonly occurring
      adverse events were respiratory infection, sinusitis, and pharyngitis.
      CONCLUSIONS: During this 52-week, open-label study, budesonide maintained the
      improved pulmonary function and decreased oral corticosteroid use observed during
      previous double-blind treatment and was well tolerated, supporting its long-term
      use in adults and children with mild to severe persistent asthma.

PMID- 12807164
TI  - Predictors of acute asthma relapse: strategies for its prevention.

PMID- 12807166
TI  - Performance of a corticosteroid inhaler with a spacer fashioned from a plastic
      cold-drink bottle: effects of changing bottle volume.
AB  - Some clinicians advocate using metered-dose inhaler (MDI) spacers prepared from
      common household bottles. We evaluated the in vitro aerosol characteristics of
      fluticasone from the MDI alone and through spacers fashioned from 237-, 500-,
      1000-, and 1500-mL polyethylene terephlate plastic cold drink bottles using a
      cascade impactor. Ten 110-microg actuations of fluticasone were sampled into the
      impactor during each of five runs with each configuration. The primary outcomes
      were the respirable dose (i.e., quantity aerosol 1.1-4.7 microm in size) and the
      quantity trapped in the oropharynx. The mean fluticasone respirable dose from the
      MDI alone (46.2 microg/actuation) was no different (p > 0.05) compared with the
      same MDI mated to any of the bottle spacers, regardless of volume. The mean
      quantity of fluticasone trapped in the oropharynx from the MDI alone (39.2
      microg/actuation) was greater (p < 0.001) than the same MDI mated with any bottle
      spacer (range 1.5-3.5 microg/actuation). These data suggest that any of the
      bottle spacers tested would be an acceptable method to decrease the quantity of
      fluticasone that would deposit onto the oropharynx and thereby diminish the risk
      of topical adverse effects. Among the range of volumes tested, there was no
      relationship between spacer volume and respirable dose of fluticasone.

PMID- 12807167
TI  - Respiratory symptoms and cigarette smoking in 3,197 pulmonologist-based asthmatic
      patients with a highly prevalent use of inhaled corticosteroid.
AB  - The relation between smoking and risk of asthma has been well-examined; however
      little attention has been paid to the correlation between smoking and asthma
      symptoms. The aims of this study were to examine respiratory symptoms in
      asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to
      assess the effects of smoking and its cessation. A cross-sectional study of
      pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a
      questionnaire about smoking habits, the incidence and frequency of symptoms
      (sputum, cough and wheezing, night symptoms, and shortness of breath), physical
      activity interference, and medication. Although 81.4% of the patients used ICS
      according to the international guideline, 14.9% had activity interference, and
      daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were
      current and 25.1% were ex-smokers. In multiple logistic regression analysis, the
      factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2)
      age and duration of asthma; for shortness of breath. Current smokers were at a
      risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11];
      2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of
      night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath
      (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios
      in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of
      asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms,
      especially sputum. It is suggested that the effects of ICS on asthma symptoms may
      be interfered with by smoking and therefore more emphasis should be placed on
      cessation of smoking.

PMID- 12807168
TI  - Effect of rocaltrol on bone mass in patients with pulmonary disease treated with
      corticosteroids.
AB  - The aim of this study was to evaluate the effect of calcitriol on bone mass in
      patients with corticosteroid induced osteoporosis. Thirty-seven patients (26
      females, 11 males, mean age 66.4 years) with pulmonary disease under long-term
      treatment with corticosteroids (5-10 mg prednisolone daily) and
      osteopenia/osteoporosis verified by dual-energy x-ray absorptiometry (DEXA)
      measurement were enrolled into the study. Rocaltrol was prescribed to 30/37 of
      the patients, the rest of the patients (6 females, 1 male) served as controls. In
      the treatment group, there was a slight increase of bone mass in the hip and
      lumbar vertebrae (L1-L4), whereas the control group showed a decrease of bone
      mass (change rate of bone mass in patients +0.8% and +1.0%, respectively, vs. 
      1.9% and -0.3%, respectively, in the control group). The preliminary results of
      our study suggest a beneficial role for the treatment of corticosteroid induced
      osteoporosis with Rocaltrol, which is well-tolerated by patients and cost
      efficient in patient management.

PMID- 12807169
TI  - The effect of seratrodast on eosinophil cationic protein and symptoms in
      asthmatics.
AB  - Thromboxane A2 (TXA2), an arachidonate derivative, is a potent
      bronchoconstrictor; therefore, blocking TXA2 should attenuate airway narrowing.
      Seratrodast, a TXA2 receptor antagonist, is expected to be a potent
      antiasthmatic. It was reported that seratrodast reduced bronchial
      hyperresponsiveness. However, it is controversial whether it reduces airway
      inflammation. We studied some additional effects of oral seratrodast to inhaled
      corticosteroids on 10 adult asthmatics in an open-label, crossover design study.
      Eosinophil cationic protein (ECP) levels in serum and sputum, peak expiratory
      flow rate (PEF), clinical symptoms, and airway responsiveness were evaluated.
      Clinical symptom scores were improved by administration of seratrodast (p <
      0.05). The addition of seratrodast to asthmatic patients significantly improved
      mean PEF (p < 0.05). In addition, withdrawal of seratrodast resulted in
      deterioration of PEF. Airway hyperresponsiveness to acetylcholine measured by
      Astograph was improved by administration of seratrodast (p < 0.01), and returned
      to the level of "run-in period" after withdrawal. Administration of seratrodast
      decreased the concentration of ECP in sputum significantly (p < 0.05), and sputum
      ECP significantly increased again after withdrawal of (p < 0.05). These results
      suggest that seratrodast improves clinical symptoms andairway hyperresponsiveness
      by reducing airway inflammation. Seratrodast may be useful as an anti
      inflammatory agent and beneficial when added to inhaled corticosteroids in the
      treatment of bronchial asthma.

PMID- 12807170
TI  - Roles of genotypes of beta2-adrenergic receptor in the relationship between
      eosinophil counts and lung function in Taiwanese adolescents.
AB  - To examine the roles of genetic polymorphism of the beta2-adrenergic receptor
      (beta2AR) in the relationship between eosinophil (EOS) counts and eosinophil
      cationic protein (ECP) counts and lung function, we recruited a random sample
      from the 1996 nationwide survey of asthma prevalence in middle school children. A
      total of 149 subjects--42 asthmatic children, 38 asthmatics in remission (no
      reported attack for more than 12 months), and 69 nonasthmatics--completed a
      physical evaluation, pulmonary function test, and determination of EOS, ECP, and
      beta2AR genotypes at amino acids 16 and 27. Asthmatic children had higher EOS and
      ECP than did nonasthmatics. No association was found between asthma and beta2AR
      genotypes. Lung function was significantly and inversely correlated with EOS but
      not with ECP in asthmatic children. By genotype, an inverse correlation between
      lung function and EOS was found in asthmatic children with Arg16Arg or Gln27Glu.
      A nonsignificant but similar inverse correlation was found in asthmatic children
      with Arg16Gly or Gln27Gln. However, a nonsignificant but positive correlation was
      found in asthmatic children with Gly16Gly. In conclusion, we suggest that EOS is
      a better clinical indicator of airway inflammation than ECP when children are not
      having an asthma attack. The association between an increase of EOS and lower
      lung function can be differentiated by beta2AR genotypes at amino acid 16.

PMID- 12807171
TI  - TH1 and TH2 cytokine production among asthmatic children after immunotherapy.
AB  - Allergen immunotherapy results in a number of changes in clinical and
      immunological parameters. To study the kinetic influence of immunotherapy on
      cytokine production, we evaluated the ratios of Th1/Th2 for patients receiving
      mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were
      calculated based on the intracellular cytokine and surface CD4 staining of
      peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2
      ratios were detected after immunotherapy, although ratios were lower for
      asthmatic children when compared with normal controls. Cytokine production was
      also determined on supernatants from mite- or mitogen-activated PBMC cells. A
      significantly increased production of all cytokines was detected from activated
      PBMC from patients after immunotherapy. Thus hyposensitization with mite extract
      for 1 year might improve the cytokine production capacity of asthma patients'
      PBMC.

PMID- 12807172
TI  - Asthma health status: influence of disease severity categorized by peak
      expiratory flow.
AB  - To evaluate the health status of patients with stable asthma and determine how
      disease severity affects the status, 68 consecutive patients were recruited from
      an outpatient clinic at an university hospital. Health status was assessed with
      the St. George's Respiratory Questionnaire and the Asthma Quality of Life
      Questionnaire (AQLQ). The results of the questionnaires revealed that the mean %
      predicted peak expiratory flow (PEF) in the preceding 2 weeks correlated most
      significantly with each total score for the two health status measures. We also
      found that, in the groups classified by mean % predicted PEF (mild, PEF > or =
      80%; moderate, 60 to 79%; severe, < 60%), there were significant differences in
      all SGRQ scores (p < 0.05). In a subgroup analysis, the scores for moderate and
      severe patients were significantly worse than for mild patients in all four
      components (p < 0.05). Almost the same tendency was observed in the score
      distribution on the AQLQ. We conclude that mean % predicted PEF correlated most
      with the health status of the patients. Patients with PEF higher than 80% of
      predicted value generally maintained a better health status than did those with
      less than 80% of predicted PEF. Achieving higher than 80% of predicted PEF is
      important in managing asthma from the viewpoint of health status.

PMID- 12807173
TI  - Children's use of emergency departments for asthma: persistent barriers or acute
      need?
AB  - Our objective was to explore, in a predominantly Latino inner-city population,
      why caregivers bring their children with asthma to the ED (emergency department).
      We conducted bilingual parent surveys and medical chart abstractions of a
      consecutive ED sample consisting of 234 children with asthma (69% Latino; 54%
      Spanish-speaking) and their caregivers. Outcome measures included: (1) the acute
      need for ED services based on objective physiological measures, (2) the extent to
      which these children experienced barriers to quality primary care for asthma
      before the ED visit, and (3) the relative importance caregivers assigned to
      worsening symptoms versus perceived barriers to non-ED care when deciding to
      bring their child to the ED. Most children had moderate or severe asthma attacks.
      In the prior month, only 33% went to a primary care provider, 83% had used a
      bronchodilator, and 63%, an age-appropriate spacer device. Seventy-five percent
      of caregivers cited perceived acute need, instead of barriers to primary care, as
      the most important reason for using the ED. This perception of acute need was
      associated with moderate or severe asthma attacks according to objective
      physiological measures, after controlling for health and sociodemographic
      characteristics. Children with asthma who use the ED encounter barriers to
      primary care, but caregivers' perception of acute need--validated by independent
      measures of attack severity--dominates caregivers' decision to use the ED.
      Ensuring continuity of care for children with asthma would involve not only
      improving various aspects of access to and quality of primary non-ED care-
      including parent education about early recognition and treatment of asthma
      attacks--but also providing families with practical low-cost alternatives for 24
      hour care and assuring linkages between the ED and sources of primary care.

PMID- 12807174
TI  - Steroid-naive adolescents with mild intermittent allergic asthma have airway
      hyperresponsiveness and elevated exhaled nitric oxide levels.
AB  - Although atopic asthma symptoms often seem to disappear around puberty, subjects
      in this age group may experience unexpected, often severe, asthma attacks. This
      may be related to persistence of untreated airway
      hyperresponsiveness/inflammation in a life period characterized by low
      perceptiveness of disease-related symptoms. This study was designed to evaluate
      the prevalence and the severity of bronchial hyperreactivity and the exhaled
      nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents.
      Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16,
      sensitized to house dust mites; 22 age-matched controls, were also studied.
      Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly
      different from controls, (p > 0.05, each comparison). By contrast, although none
      of the control subjects showed bronchial hyperreactivity, increased airway
      responsiveness to methacholine (MCh) was demonstrated in the majority of the
      patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or
      accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400
      microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations
      were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3
      ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO
      levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control
      subjects). A positive, statistically significant correlation was found between
      FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r =
      0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness
      and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary
      function parameters (p > 0.05). The high incidence of bronchial
      hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the
      elevated FENO levels) in adolescents with mild asthma suggests the need for more
      accurate evaluation and, possibly, for early intervention with antiinflammatory
      drugs in a significant proportion of patients in this age group.

PMID- 12807175
TI  - Interrater agreement in the clinical evaluation of acute pediatric asthma.
AB  - Prior studies of observer agreement of the clinical exam of children with asthma
      have focused on small numbers of specially trained observers, often in the
      setting of clinical trials. Our objective was to evaluate interobserver
      reliability in the physical exam of acute pediatric wheezing and asthma among a
      large group of diverse examiners, in a setting of routine clinical practice, and
      without prior special training. The setting was a large urban children's
      hospital. Observers were attending pediatric emergency physicians and fellows;
      hospital respiratory therapists; and emergency department (ED) nurses. Patients
      were children receiving nebulized medications for wheezing in the ED or inpatient
      asthma unit. Pairs of observers simultaneously but independently rated work of
      breathing, wheeze, decreased air entry, prolonged expiration, breathlessness,
      respiratory rate, mental status, and global (or overall) severity using a
      structured exam template. A total score for each exam was also evaluated. A total
      of 230 pairs of observations were performed; mean patient age was 5.3 years. For
      all pairs, the weighted kappa statistics for the exam components ranged from 0.61
      to 0.74 (moderate or substantial agreement). The global severity category and
      total score had weighted kappas of 0.80 and 0.82, respectively (excellent
      agreement). Agreement was generally somewhat lower for unlike (different
      profession) observer pairs than for like observer pairs, but remained acceptable.
      Agreement in two age groups (< or = 3 years old and > or = 4) was at least
      moderate for all exam components analyzed. Spearman rank correlations between
      individual exam components and the global assessments of patient severity were
      all greater than 0.5, indicating at least moderate to good correlations. We found
      substantial interobserver agreement among a broad range of examiners in the
      components of the clinical examination of acute wheezing in both younger and
      older children. This is contrary to the commonly held observation that the poor
      interobserver reliability of physical exam findings in asthma may limit their
      usefulness as asthma outcome measures. Support for use of a structured
      respiratory exam format or template in asthma guidelines was also shown.

PMID- 12807176
TI  - Asthma, age, and early reversibility testing.
AB  - The aim of this study was to assess the effect of age on early reversibility
      testing (ERT) in patients with asthma. Forty-nine nonsmokers with asthma were
      investigated. In all cases, disease duration was less than 15 years; the absolute
      change (absolute variability, AV) in forced expiratory volume in 1 second (FEV1)
      on ERT was greater than 100 mL; and the increase in FEV1 on ERT was greater than
      10%. Patients were categorized as group I (younger than 50 years; n = 24) and
      group II (50 years or older; n = 25). There were no significant differences
      between the groups regarding disease duration and severity. The mean patient ages
      in groups I and II were 40.3 +/- 7.9 years and 59.2 +/- 7.1 years, respectively,
      and the corresponding mean baseline FEV1 values were 62.2 +/- 23.7% and 67.4 +/-
      21.1% of predicted value (p > 0.05). Pulmonary function tests were performed at
      baseline, and then repeated for ERT 20 minutes after inhalation of 200 microg
      salbutamol. After ERT, the respective findings for groups I and II were as
      follows: AV 412 +/- 184 mL and 247 +/- 138 mL; percentage change (PC) in FEV1
      21.5 +/- 9.3% and 16.9 +/- 7.5%; and percent of predicted change (PPC) in FEV1
      13.6 +/- 6.5% and 9.9 +/- 4.9%. The AV, PC, and PPC values for group I all were
      higher than the corresponding findings for group II, and the differences in AV
      and PPC were statistically significant (p = 0.001, p < 0.05). The study showed
      that elderly asthma patients exhibit significantly lower AV and PPC after ERT. To
      improve the accuracy of asthma diagnosis in elderly patients, limits of ERT
      should be redefined.

PMID- 12807177
TI  - Assessment of breathlessness perception by Borg scale in asthmatic patients:
      reproducibility and applicability to different stimuli.
AB  - In asthmatics, the score of bronchoconstriction-associated breathlessness at 20%
      fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale
      (PS20) is a tool successfully used to measure the perception of symptoms. This
      prospective laboratory study evaluated the applicability of PS20 to assess the
      breathlessness induced by ultrasonically nebulized distilled water (UNDW) and
      methacholine (M) and its reproducibility. Twenty-two mild and clinically stable
      asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated
      by linear interpolation of the last two points of the perception/fall in FEV1
      curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by
      repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did
      not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were
      significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and PS20 M
      was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The intraclass
      correlation coefficient for repeated measurement of PS20 M was 0.82; the bias
      between the two measurements was 0.2 with the limits of agreement ranging from 
      2.8 to 3.2. All patients had a measurable breathlessness perception degree on a
      Borg scale during both distilled water challenges and methacholine. Asthmatic
      patients with normal, exaggerated or poor breathlessness perception were also
      similar for both stimuli. In addition, PS20 showed a good reproducibility and
      this allows the serial evaluation of patient's breathlessness perception by this
      technique in clinical settings and in the physiology laboratory.

PMID- 12807178
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.

PMID- 12807179
TI  - Notification that new names and new combinations have appeared in Volume 53, Part
      1, of the IJSEM.

PMID- 12807180
TI  - Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus
      complex and related species: description of Streptococcus gallolyticus subsp.
      gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S.
      gallolyticus subsp. pasteurianus subsp. nov.
AB  - 'Streptococcus bovis/Streptococcus equinus' is a large bacterial complex
      including different species frequently isolated from infections of humans
      (Streptococcus gallolyticus, Streptococcus infantarius) or animals (S. bovis, S.
      equinus, Streptococcus alactolyticus). The separation of S. bovis into three
      different biotypes has been partially correlated with genetic differentiation. In
      addition, recent advances in bacterial phylogeny have led to the inclusion of
      Streptococcus macedonicus and Streptococcus waius in this complex. The aim of
      this study was to improve physiological differentiation between species related
      to the complex and to clarify their respective phylogenetic positions. In this
      study, physiological, genetic and phylogenetic analyses of a set of 88
      streptococcal strains were performed. The diversity of strains of S. bovis
      biotype II was analysed, and it was confirmed that they belong to different
      species, either S. equinus or S. infantarius. It was demonstrated that S.
      gallolyticus, S. bovis biotype II.2, S. macedonicus and S. waius form a single
      DNA cluster separated into three different subspecies. They are delineated by
      different biochemical traits, limited DNA-DNA relatedness and noticeable
      divergence in 16S rDNA sequences. According to the current definition of species,
      the names S. gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp.
      pasteurianus subsp. nov. and S. gallolyticus subsp. macedonicus subsp. nov. are
      proposed for these three subspecies.

PMID- 12807181
TI  - Glaciecola mesophila sp. nov., a novel marine agar-digesting bacterium.
AB  - Alteromonas-like strains KMM 241(T) and KMM 642, isolated from marine
      invertebrate specimens, were investigated to clarify their taxonomic position.
      The novel isolates were aerobic, Gram-negative, motile, slightly halophilic and
      heterotrophic and hydrolysed polysaccharides. They did not hydrolyse urea,
      gelatin or casein and produced acid weakly from carbohydrates. The DNA G + C
      content ranged between 44.6 and 44.8 mol%. DNA-DNA similarity between the two
      strains was 71%. Comparison of the 16S rRNA gene sequence of strain KMM 241(T)
      revealed 94.5-94.8% similarity to Glaciecola species. The novel strains shared
      several phenotypic and physiological properties with members of Glaciecola, but
      they differed in their lack of pigment production, their minimal and maximal
      growth temperatures and their ability to hydrolyse agar and carrageenan and in
      the utilization of organic compounds. On the basis of phenotypic and
      physiological characteristics as well as phylogenetic analysis, the isolates
      should be assigned to a novel species, Glaciecola mesophila sp. nov. The type
      strain is strain KMM 241(T) (=DSM 15026(T)).

PMID- 12807182
TI  - Saccharospirillum impatiens gen. nov., sp. nov., a novel gamma-Proteobacterium
      isolated from hypersaline Ekho Lake (East Antarctica).
AB  - Five Gram-negative, motile, aerobic to microaerophilic spirilla were isolated
      from various depths of the hypersaline, heliothermal and meromictic Ekho Lake
      (East Antarctica). The strains are oxidase- and catalase-positive, metabolize a
      variety of sugars and carboxylic acids and have an absolute requirement for
      sodium ions. The predominant fatty acids of the organisms are C(16 : 1)omega7c,
      C(16 : 0) and C(18 : 1)omega7c, with C(10 : 1))3-OH, C(10 : 0) 3-OH, C(12 : 0) 3
      OH, C(14 : 1)3-OH, C(14 : 0) 3-OH and C(19 : 1) present in smaller amounts. The
      main polar lipids are diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol and phosphatidylmonomethylamine. The DNA base composition of
      the strains is 54-55 mol% G + C. 16S rRNA gene sequence comparisons show that the
      isolates are related to the genera Oceanospirillum, Pseudospirillum,
      Marinospirillum, Halomonas and Chromohalobacter in the gamma-Proteobacteria.
      Morphological, physiological and genotypic differences from these previously
      described genera support the description of a novel genus and species,
      Saccharospirillum impatiens gen. nov., sp. nov. The type strain is EL-105(T)
      (=DSM 12546(T) = CECT 5721(T)).

PMID- 12807183
TI  - Recognition of two genetic groups in the Klebsiella oxytoca taxon on the basis of
      chromosomal beta-lactamase and housekeeping gene sequences as well as ERIC-1 R
      PCR typing.
AB  - Whilst searching for a molecular method to identify the different species of
      Raoultella and Klebsiella oxytoca, it was observed that the OXY-1 and OXY-2 beta
      lactamase-producing K. oxytoca isolates displayed two distinguishable
      enterobacterial repetitive intergenic consensus (ERIC)-1R profiles. It was
      hypothesized that the two groups of chromosomal beta-lactamases might correspond
      to two groups of strains in the K. oxytoca taxon. To confirm this hypothesis,
      clinical isolates and reference strains of K. oxytoca were studied by
      determination of the sequence of their bla(OXY) genes, and of a partial fragment
      of their 16S rRNA (387 bp) and rpoB (512 bp) genes. The sequence data were
      phylogenetically analysed by using the parsimony method. Four clinical isolates
      possessed a bla(OXY-1) gene and nine possessed a bla(OXY-2) gene. The mean
      percentage of rpoB and 16S rRNA gene identity was > 99% within each group of
      strains, whereas it was 96.56 +/- 0.24% for rpoB genes and 97.80 +/- 0.22% for
      16S rRNA genes between the group of strains harbouring the bla(OXY-1) gene and
      the group harbouring the bla(OXY-2) gene. The phylogenetic tree resulting from
      combined analysis of the 16S rRNA and rpoB datasets showed that the K. oxytoca
      isolates were monophyletic and separated into two clades; these clades included
      strains with either the bla(OXY-1) gene or the bla(OXY-2) gene. This result was
      supported with high bootstrap values of 97 and 99%, respectively. Moreover, the
      two groups of strains displayed distinct ERIC-1R profiles, with bands
      characteristic of each profile. Thus, the chromosomal bla(OXY) gene sequence is
      able to delineate not only two groups of beta-lactamases in K. oxytoca, but also
      two clades in the K. oxytoca taxon, in a manner similar to the sequence of
      housekeeping genes. These results suggest that K. oxytoca should be divided into
      two genetic groups, group OXY-1 represented by K. oxytoca strain SL781 (=CIP
      104963) and group OXY-2 by K. oxytoca strain SL91l (= CIP 106098).

PMID- 12807184
TI  - Rhodoferax ferrireducens sp. nov., a psychrotolerant, facultatively anaerobic
      bacterium that oxidizes acetate with the reduction of Fe(III).
AB  - To further investigate the diversity of micro-organisms capable of conserving
      energy to support growth from dissimilatory Fe(III) reduction, Fe(III)-reducing
      micro-organisms were enriched and isolated from subsurface sediments collected in
      Oyster Bay, VA, USA. A novel isolate, designated T118(T), was recovered in a
      medium with lactate as the sole electron donor and Fe(III) as the sole electron
      acceptor. Cells of T1 18(T) were Gram-negative, motile, short rods with a single
      polar flagellum. Strain T1 18(T) grew between pH 6.7 and 7.1, with a temperature
      range of 4-30 degrees C. The optimal growth temperature was 25 degrees C.
      Electron donors utilized by strain T1 18(T) with Fe(III) as the sole electron
      acceptor included acetate, lactate, malate, propionate, pyruvate, succinate and
      benzoate. None of the compounds tested was fermented. Electron acceptors utilized
      with either acetate or lactate as the electron donor included Fe(III)-NTA
      (nitrilotriacetic acid), Mn(IV) oxide, nitrate, fumarate and oxygen. Phylogenetic
      analysis demonstrated that strain T1 18(T) is most closely related to the genus
      Rhodoferax. Unlike other species in this genus, strain T1 18(T) is not a
      phototroph and does not ferment fructose. However, phototrophic genes may be
      present but not expressed under the experimental conditions tested. No Rhodoferax
      species have been reported to grow via dissimilatory Fe(III) reduction. Based on
      these physiological and phylogenetic differences, strain T1 18(T) (=ATCC BAA
      621(T) = DSM 15236(T)) is proposed as a novel species, Rhodoferax ferrireducens
      sp. nov.

PMID- 12807185
TI  - Reclassification of Lactobacillus maltaromicus (Miller et al. 1974) DSM 20342(T)
      and DSM 20344 and Carnobacterium piscicola (Collins et al. 1987) DSM 20730(T) and
      DSM 20722 as Carnobacterium maltaromaticum comb. nov.
AB  - Phenotypic and genotypic characterizations of Lactobacillus maltaromicus strains
      DSM 20342(T) and DSM 20344 provided evidence for the reclassification of this
      species in the genus Carnobacterium. Moreover, phenotypic and genotypic
      comparisons made between L. maltaromicus and Carnobacterium piscicola highlighted
      that these two species should be considered synonyms. For these reasons, the
      species Carnobacterium maltaromaticum comb. nov. (type strain DSM 20342(T) = ATCC
      27865(T) = CCUG 30142(T) = CIP 103135(T) = JCM 1154(T) = LMG 6903(T) = NRRL B
      14852(T)) is proposed to accommodate L. maltaromicus and C. piscicola.

PMID- 12807186
TI  - Actinobaculum urinale sp. nov., from human urine.
AB  - A hitherto undescribed Actinomyces-like bacterium was isolated from human urine.
      Based on its biochemical characteristics, the unidentified bacterium did not
      correspond to any currently described Actinomyces species or related taxa.
      Comparative 16S rRNA gene sequencing showed that the unknown bacterium exhibits a
      specific phylogenetic association with the genus Actinobaculum, but a sequence
      divergence of > 5% from the two currently recognized members of this genus,
      Actinobaculum schaalii and Actinobaculum suis, demonstrates that it represents a
      distinct species. Based on both phenotypic and 16S rRNA gene sequence
      considerations, it is proposed that the unknown bacterium from urine should be
      classified as a novel species, Actinobaculum urinale sp. nov. The type strain of
      Actinobaculum urinale is CCUG 46093(T) (= CIP 107424(T)).

PMID- 12807187
TI  - Enterococcus phoeniculicola sp. nov., a novel member of the enterococci isolated
      from the uropygial gland of the Red-billed Woodhoopoe, Phoeniculus purpureus.
AB  - A facultatively anaerobic, Gram-positive, coccoid, non-spore-forming, non-motile,
      catalase-negative bacterium was isolated from the uropygial (preen) gland of wild
      Red-billed Woodhoopoes (Phoeniculus purpureus) and designated strain JLB-1(T).
      Physiological and biochemical testing suggested that this homofermentative,
      lactic-acid-producing bacterium could belong to the genus Enterococcus or the
      genus Streptococcus. Comparison of the 16S rRNA gene sequence of strain JLB-1(T)
      with other 16S rDNA sequences in the GenBank database by BLAST analysis showed
      that its closest relatives are Enterococcus faecium, Enterococcus avium and
      Enterococcus asini. Strain JLB-1(T) may be differentiated from these species by
      the fact that it does not produce acid from lactose, D-mannitol, D(+)-melezitose
      or D-sorbitol. Furthermore, it does not hydrolyse arginine or hippurate and
      cannot grow in the presence of 6.5% NaCl or 40% bile. It differs from the
      streptococci in that it does not lyse erythrocytes. Strain JLB-1(T) is a novel
      member of the enterococci, for which the name Enterococcus phoeniculicola sp.
      nov. is proposed. The type strain is JLB-1(T) (=ATCC BAA-412(T) = DSM 14726(T)).

PMID- 12807188
TI  - Halobacillus salinus sp. nov., isolated from a salt lake on the coast of the East
      Sea in Korea.
AB  - A Gram-positive, rod-shaped, endospore-forming, halophilic bacterium (strain HSL
      3(T)) was isolated from a salt lake near Hwajinpo beach on the East Sea in Korea
      and was subjected to a polyphasic taxonomic study. Strain HSL-3(T) grew optimally
      in the presence of 2-10% (w/v) NaCl. Strain HSL-3(T) showed poor growth in the
      absence of NaCl and grew in the presence of less than 23% NaCl. The cell wall
      peptidoglycan type of strain HSL-3(T) was A4beta based on L-Orn-D-Asp. The
      predominant menaquinone found in strain HSL-3(T) was menaquinone-7 (MK-7). Strain
      HSL-3(T) had a cellular fatty acid profile containing large amounts of branched
      fatty acids; the major fatty acids were anteiso-C(15 : 0), iso-C(15 : 0) and iso
      C(16 : 0). The DNA G + C content of strain HSL-3(T) was 45 mol%. Phylogenetic
      analysis based on 16S rDNA sequences showed that strain HSL-3(T) falls within the
      radiation of the cluster comprising Halobacillus species. Strain HSL-3(T)
      exhibited levels of 16S rDNA similarity of 97.4-98.4% to the type strains of
      Halobacillus species. Levels of DNA-DNA relatedness between strain HSL-3(T) and
      the type strains of all validly named Halobacillus species were in the range 7.3
      9.2%. On the basis of phenotypic and phylogenetic data and the genomic
      distinctiveness, strain HSL-3(T) (= KCCM 41590(T) = JCM 11546(T)) should be
      placed in the genus Halobacillus as the type strain of a novel species, for which
      the name Halobacillus salinus sp. nov. is proposed.

PMID- 12807189
TI  - Phylogenetic relationships between Bacillus species and related genera inferred
      from comparison of 3' end 16S rDNA and 5' end 16S-23S ITS nucleotide sequences.
AB  - The nucleotide sequences of the 3' end of the 16S rDNA and the 16S-23S internal
      transcribed spacer (ITS) of 40 Bacillaceae species were determined. These
      included 21 Bacillus, 9 Paenibacillus, 6 Brevibacillus, 2 Geobacillus, 1
      Marinibacillus and 1 Virgibacillus species. Comparative sequence analysis of a
      220 bp region covering a highly conserved 150 bp sequence located at the 3' end
      of the 16S rRNA coding region and a conserved 70 bp sequence located at the 5'
      end of the 16S-23S ITS of the 40 species and six sequences available in GenBank
      were used to infer the phylogenetic relationships between all 46 taxa. When a
      maximal distance (D(max), where D refers to the number of nucleotide
      substitutions per site) of 0.31 was introduced as a threshold to determine
      groupings, 10 phylogenetically distinct clusters were revealed. Twenty-six
      Bacillus species were separated in seven groups (I, II, III, IV, V, VI and X),
      but Bacillus circulans remained ungrouped. All six Brevibacillus species under
      study were in Group VII. The nine Paenibacillus species fell into two distinct
      groups (VIII and IX). Species with D(max) values within 0.05 were considered to
      be very closely related. These were Bacillus psychrophilus and Bacillus
      psychrosaccharolyticus in Group II; 'Bacillus maroccanus' and Bacillus simplex in
      Group II; Bacillus amyloliquefaciens, Bacillus atrophaeus, Bacillus mojavensis
      and Bacillus subtilis in Group VI; Bacillus fusiformis and Bacillus sphaericus in
      Group VI; Brevibacillus brevis and Brevibacillus formosus in Group VII;
      Paenibacillus gordonae and Paenibacillus validus in Group VIII; and Bacillus
      anthracis, Bacillus cereus, Bacillus mycoides and Bacillus thuringiensis in Group
      X. The phylogenetic classification presented here is, in general, in agreement
      with current classifications based on phenotypic and molecular data. Our findings
      suggest, however, that in some cases, further divisions or, conversely, further
      groupings might be warranted. Should current classifications be re-examined in
      the light of our results, D(max) values of 0.31 and 0.05, as exemplified here,
      may prove useful threshold values for the grouping of Bacillaceae into taxa akin
      to genera and species, respectively. These D(max) thresholds may also reveal, in
      a different way, bacterial species for which further characterization might be
      warranted for proper classification and/or reassignment.

PMID- 12807190
TI  - Corynebacterium glaucum sp. nov.
AB  - A bacterial strain, strain IMMIB R-5091(T), isolated from a cosmetic dye was
      characterized by phenotypic and molecular taxonomic methods. Chemotaxonomic
      investigations revealed the presence of cell-wall chemotype IV and short-chain
      mycolic acids consistent with the genus Corynebacterium. Comparative 16S rRNA
      gene sequencing showed that the isolate constitutes a distinct subline within the
      genus Corynebacterium, displaying > 2.6% sequence divergence from established
      species. The isolate could be distinguished from other members of the genus
      Corynebacterium by biochemical tests. Based on both phenotypic and phylogenetic
      evidence, it is proposed that strain IMMIB R-5091(T) (= DSM 44530T = NRRL B
      24142(T)) be classified as the type strain of a novel species, Corynebacterium
      glaucum sp. nov.

PMID- 12807191
TI  - Marinilactibacillus psychrotolerans gen. nov., sp. nov., a halophilic and
      alkaliphilic marine lactic acid bacterium isolated from marine organisms in
      temperate and subtropical areas of Japan.
AB  - A novel marine lactic acid rod bacterium has been described for eight strains
      isolated from living and decomposing marine organisms collected from temperate
      and subtropical areas of Japan. The isolates were Gram-positive, catalase
      negative, non-sporulating and motile with peritrichous flagella. They were
      slightly halophilic, highly halotolerant and alkaliphilic; the optimum NaCl
      concentration for growth was 2.0-3.75% (w/v) with a range from 0 to 17.0-20.5%
      (depending on the strain); the optimum pH was between 8.0 and 9.5 with a range
      from 6.0 to 10.0. They were psychrotolerant, growing well at -1.8 degrees C with
      a maximum at 40-45 degrees C and the optimum at 37-40 degrees C. Lactate yields
      were 87-100% per consumed glucose; the residual products were formate, acetate
      and ethanol with a molar ratio of approximately 2 : 1 : 1. The product
      composition was markedly affected by the pH of fermentation medium; at higher pH,
      the yield of lactate decreased (60-65% at pH 9.0) and that of other products
      increased conversely. The cell-wall peptidoglycan type was type A4beta, Orn-D
      Glu, whereas that of the genus Alkalibacterium, the phylogenetically closest
      lactic acid bacterium, was type A4beta, Orn-D-Asp. The major cellular fatty acids
      were C16 : 0, C16 : 1delta9, C18 : 0 and C18 : 1delta9 (oleic acid). The G + C
      content of the DNA was 34.6-36.2 mol%. The eight isolates were phenotypically
      homogeneous and formed a single genomic species. The 16S rRNA gene sequence
      analysis indicated that the isolates constituted an independent phylogenetic
      lineage within the radiation of lactic acid bacteria with 96.2% similarity to the
      genus Alkalibacterium. The secondary structure and the nucleotide sequence of the
      V6 region of the 16S rRNA were characteristic of the organism among other related
      lactic acid genera. On the bases of phenotypic and phylogenetic distinctness, the
      organism was proposed to belong to a new genus and species, Marinilactibacillus
      psychrotolerans gen. nov., sp. nov. The type strain, M13-2(T) (G + C = 36.2
      mol%), has been deposited in the IAM, NBRC, NCIMB and NRIC culture collections as
      IAM 14980(T), NBRC 100002(T), NCIMB 13873(T) and NRIC 0510(T), respectively.

PMID- 12807193
TI  - Bacillus barbaricus sp. nov., isolated from an experimental wall painting.
AB  - In a project concerning bacterial colonization of experimental wall paintings, a
      large number of isolates have been acquired with high similarities in their whole
      cell protein patterns obtained after SDS-PAGE. Of this group, four strains,
      designated V2-BIII-A2(T), V2-BI-A9, V2-BI-04 and V2-BII-A8, were chosen for
      further characterization. Banding patterns obtained after ERIC-PCR were barely
      distinguishable among these four strains, indicating their affiliation within a
      single species. The isolates also displayed nearly identical biochemical and
      physiological features. The chemotaxonomic characteristics, including polar
      lipids, quinone systems, cell-wall diamino acid composition and fatty acid
      profiles, were in good agreement with those of numerous previously described
      Bacillus species. 16S rDNA analysis of strain V2-BIII-A2(T) showed that this
      bacterium belongs to the genus Bacillus, with highest sequence similarities to
      Bacillus megaterium (94.6%), Bacillus flexus (94.4%) and the alkaliphilic
      Bacillus cohnii (94.2%). Based on almost identical biochemical, physiological and
      chemotaxonomic traits, ERIC-PCR-generated genomic fingerprints and comparative
      16S rDNA sequence analysis, it is demonstrated that the four isolates represent a
      novel species of the genus Bacillus, for which the name Bacillus barbaricus sp.
      nov. is proposed. The type strain is V2-BIII-A2(T) (= CCM 4982(T) = DSM
      14730(T)).

PMID- 12807194
TI  - Jannaschia helgolandensis gen. nov., sp. nov., a novel abundant member of the
      marine Roseobacter clade from the North Sea.
AB  - Heterotrophic bacteria were isolated from a water sample taken from the North
      Sea, 2 km off the coast of the island of Helgoland, by direct plating of the
      serially diluted sample on complex marine media. Sixteen of 80 strains from the
      highest sample dilution belonged to the 'Roseobacter-Sulfitobacter-Silicibacter'
      group within the 2-subclass of the Proteobacteria on the basis of partial 16S
      rDNA sequence analysis. Phylogenetic analysis of nearly complete 16S rDNA
      sequences showed that the closest relative of two strains, Hel 10(T) and Hel 26,
      was Ketogulonicigenium vulgare (94.4% similarity). These strains were Gram
      negative, non-motile rods, obligate aerobes, required sodium ions and 1-7% sea
      salts for growth and did not produce bacteriochlorophyll. Their optimal growth
      temperature was 25-30 degrees C. The strains had Q-10 as the dominant respiratory
      quinone. Chemotaxonomic analysis showed a combination of ester-linked 3-OH 10 :
      0, 12 : 1 and amide-linked 3-oxo 14 : 0 (or 3-OH 14 : 1) and 3-OH 14 : 0 fatty
      acids, which appears to be a unique feature of strains Hel 10(T) and Hel 26
      within this subsection of the 2-subclass of the Proteobacteria. Based on 16S rDNA
      sequence analysis and chemotaxonomic data, the strains are assigned to a new
      genus and species, Jannaschia helgolandensis gen. nov., sp. nov., with the type
      strain Hel 10(T) (= DSM 14858(T) = NCIMB 13941(T)).

PMID- 12807192
TI  - Actinomadura namibiensis sp. nov.
AB  - Strain HAG 010767(T) was isolated from desert soil from Namibia during a
      screening programme. On the basis of analysis of 16S rDNA, the principal amino
      acid of the peptidoglycan, cell-wall sugars, fatty acids and polar lipids, it was
      possible to identify this strain as a member of the genus Actinomadura. Although
      DNA-DNA reassociation experiments revealed 72% DNA similarity between strain HAG
      010767(T) and Actinomadura kijaniata DSM 43764(T), significant differences in the
      colour of the mycelium and physiological properties indicate that strain HAG
      010767(T) represents a novel species of this genus, for which the name
      Actinomadura namibiensis sp. nov. is proposed. The type strain is strain HAG
      010767(T) (= DSM 44197(T) = NRRL B-24153(T)).

PMID- 12807195
TI  - DNA-DNA hybridization study of Burkholderia species using genomic DNA macro-array
      analysis coupled to reverse genome probing.
AB  - The present study was aimed at simplifying procedures to delineate species and
      identify isolates based on DNA-DNA reassociation. DNA macro-arrays harbouring
      genomic DNA of reference strains of several Burkholderia species were produced.
      Labelled genomic DNA, hybridized to such an array, allowed multiple relative
      pairwise comparisons. Based on the relative DNA-DNA relatedness values, a
      complete data matrix was constructed and the ability of the method to
      discriminate strains belonging to different species was assessed. This simple
      approach led successfully to the discrimination of Burkholderia mallei from
      Burkholderia pseudomallei, but also discriminated Burkholderia cepacia genomovars
      I and III, Burkholderia multivorans, Burkholderia pyrrocinia, Burkholderia
      stabilis and Burkholderia vietnamiensis. Present data showed a sufficient degree
      of congruence with previous DNA-DNA reassociation techniques. As part of a
      polyphasic taxonomic scheme, this straightforward approach is proposed to improve
      species definition, especially for application in the rapid screening necessary
      for large numbers of clinical or environmental isolates.

PMID- 12807196
TI  - Oceanithermus profundus gen. nov., sp. nov., a thermophilic, microaerophilic,
      facultatively chemolithoheterotrophic bacterium from a deep-sea hydrothermal
      vent.
AB  - A novel moderately thermophilic, organotrophic, microaerophilic, facultatively
      chemolithotrophic bacterium, designated strain 506(T), was isolated from a deep
      sea hydrothermal vent site at 13 degrees N in the East Pacific Rise. Cells were
      Gram-negative, non-motile rods. The organism grew in the temperature range 40-68
      degrees C, with an optimum at 60 degrees C, and in the pH range 5.5-8.4, with an
      optimum around pH 7.5. The NaCl concentration for growth was in the range 10-50 g
      l(-1), with an optimum at 30 g l(-1). Strain 506(T) grew
      chemoorganoheterotrophically with carbohydrates, proteinaceous substrates,
      organic acids and alcohols using oxygen or nitrate as electron acceptor.
      Alternatively, strain 506(T) was able to grow lithoheterotrophically with
      molecular hydrogen as the energy source. The G +C content of the genomic DNA was
      62.9 mol%. Phylogenetic analysis of the 16S rDNA sequence placed strain 506(T) in
      the family Thermaceae. On the basis of phenotypic and phylogenetic data, strain
      506(T) (= DSM 14977(T) = VKM B-2274(T)) is proposed as the type strain of a novel
      species in a new genus, Oceanithermus profundus gen. nov., sp. nov.

PMID- 12807197
TI  - Vibrio kanaloae sp. nov., Vibrio pomeroyi sp. nov. and Vibrio chagasii sp. nov.,
      from sea water and marine animals.
AB  - The taxonomic position of the fluorescent amplified fragment length polymorphism
      fingerprinting groups A46 (five isolates), A51 (six isolates), A52 (five
      isolates) and A53 (seven isolates) obtained in a previous study were further
      analysed through a polyphasic approach. The 23 isolates were phylogenetically
      related to Vibrio splendidus, but DNA-DNA hybridization experiments proved that
      they belong to three novel species. Chemotaxonomic and phenotypic analyses
      further disclosed several features that differentiate between the 23 isolates and
      known Vibrio species. The names Vibrio kanaloae sp. nov. (type strain LMG
      20539(T) = CAIM 485(T); EMBL accession no. AJ316193; G + C content 44.7 mol%),
      Vibrio pomeroyi sp. nov. (type strain LMG 20537(T) = CAIM 578(T); EMBL accession
      no. AJ491290; G +C content 44.1 mol%) and Vibrio chagasii sp. nov. (type strain
      LMG 21353(T) = CAIM 431(T); EMBL accession no. AJ316199; G + C content 44.6 mol%)
      are respectively proposed to encompass the five isolates of A46, the six isolates
      of A51 and the 12 isolates of A52/A53. The three novel species can be
      distinguished from known Vibrio species by several phenotypic features, including
      utilization and fermentation of various carbon sources, beta-galactosidase
      activity and fatty acid content (particularly of 12 : 0, 14: 0, 14 : 0 iso and 16
      : 0 iso).

PMID- 12807198
TI  - Missing links in the divergence of Chlamydophila abortus from Chlamydophila
      psittaci.
AB  - Pathological and serological evidence and DNA-DNA reassociation data indicate
      that Chlamydophila psittaci and Chlamydophila abortus are separate species. C.
      psittaci causes avian systemic disease and C. abortus causes abortion. Both
      previously belonged to Chlamydia psittaci are associated with zoonotic and
      enzootic outbreaks. Genetic studies suggest that they are closely related and
      because of the recent availability of diverse C. psittaci strains and comparative
      data for several genes, it was possible to explore this relationship. The parrot
      C. psittaci strain 84/2334 was found to have DNA sequences that were identical to
      an extrachromosomal plasmid in duck C. psittaci strain N352, to rnpB in strain
      R54 from a brown skua and to the rrn intergenic spacer in parakeet strain
      Prk/Daruma (from Germany, Antarctica and Japan, respectively). Analysis of ompA
      and the rrn spacer revealed progressive diversification of the strains, with
      84/2334 resembling what might have been a recent ancestor of C. abortus. Another
      C. psittaci strain (VS225) showed evidence of having undergone convergent
      evolution towards the C. abortus-like genotype, whereas strain R54 diverged
      independently. For the first time, these studies link C. abortus in an
      evolutionary context to the C. psittaci lineage. It has been concluded that C.
      abortus diverged from C. psittaci, and so strain R54 was designated a C. psittaci
      strain. It is recommended that characterization of C. psittaci and C. abortus
      strains should utilize more than a single method and more than a single gene.

PMID- 12807199
TI  - Chryseobacterium joostei sp. nov., isolated from the dairy environment.
AB  - Among a large collection of South African dairy isolates, a novel
      Chryseobacterium taxon (DNA group 3) was previously delineated by a polyphasic
      taxonomic study (Hugo et al., Syst Appl Microbiol 22, 586-595, 1999). In the
      present paper, this taxon is further characterized using 16S rDNA sequencing,
      fatty acid methyl ester analysis and a comparative phenotypic analysis, resulting
      in the proposal of a novel species, Chryseobacterium joostei sp. nov. (type
      strain Ix 5a(T) = LMG 18212(T) = CCUG 46665(T)).

PMID- 12807200
TI  - Oleispira antarctica gen. nov., sp. nov., a novel hydrocarbonoclastic marine
      bacterium isolated from Antarctic coastal sea water.
AB  - The taxonomic characteristics of two bacterial strains, RB-8(T) and RB-9,
      isolated from hydrocarbon-degrading enrichment cultures obtained from Antarctic
      coastal marine environments (Rod Bay, Ross Sea), were determined. These bacteria
      were psychrophilic, aerobic and Gram-negative with polar flagella. Growth was not
      observed in the absence of NaCl, occurred only at concentrations of Na+ above 20
      mM and was optimal at an NaCl concentration of 3-5% (w/v). The major cellular
      fatty acids were monounsaturated straight-chain fatty acids. The strains were
      able to synthesize the polyunsaturated fatty acid eicosapentaenoic acid (20:
      5omega3) at low temperatures. The DNA G + C contents were 41-42 mol%. The strains
      formed a distinct phyletic line within the gamma-Proteobacteria, with less than
      89.6% sequence identity to their closest relatives within the Bacteria with
      validly published names. Both isolates exhibited a restricted substrate profile,
      with a preference for aliphatic hydrocarbons, that is typical of marine
      hydrocarbonoclastic micro-organisms such as Alcanivorax, Marinobacter and
      Oleiphilus. On the basis of ecophysiological properties, G + C content, 16S rRNA
      gene sequences and fatty acid composition, a novel genus and species within the
      gamma-Proteobacteria are proposed, Oleispira antarctica gen. nov., sp. nov.;
      strain RB-8(T) (= DSM 14852(T) = LMG 21398(T)) is the type strain.

PMID- 12807201
TI  - Description of Sulfurospirillum halorespirans sp. nov., an anaerobic,
      tetrachloroethene-respiring bacterium, and transfer of Dehalospirillum
      multivorans to the genus Sulfurospirillum as Sulfurospirillum multivorans comb.
      nov.
AB  - An anaerobic, halorespiring bacterium (strain PCE-M2(T) = DSM 13726(T) = ATCC BAA
      583(T)) able to reduce tetrachloroethene to cis-dichloroethene was isolated from
      an anaerobic soil polluted with chlorinated aliphatic compounds. The isolate is
      assigned to the genus Sulfurospirillum as a novel species, Sulfurospirillum
      halorespirans sp. nov. Furthermore, on the basis of all available data, a related
      organism, Dehalospirillum multivorans DSM 12446(T), is reclassified to the genus
      Sulfurospirillum as Sulfurospirillum multivorans comb. nov.

PMID- 12807202
TI  - Acidovorax valerianellae sp. nov., a novel pathogen of lamb's lettuce
      [Valerianella locusta (L.) Laterr].
AB  - Bacterial spot disease of lamb's lettuce [Valerianella locusta (L.) Laterr.] was
      first observed in fields in 1991. This new bacterial disease is localized in
      western France in high-technology field production of lamb's lettuce for the
      preparation of ready-to-use salad. Nineteen strains isolated in 1992 and 1993
      from typical black leaf spots of naturally infected lamb's lettuce were
      characterized and compared with reference strains of Acidovorax and Delftia. The
      pathogenicity of the 19 strains was confirmed by artificial inoculation.
      Biochemical and physiological tests, fatty acid profiles, DNA-DNA hybridization
      and other nucleic acid-based tests were performed. A numerical taxonomic analysis
      of the 19 lamb's lettuce strains showed a single homogeneous phenon closely
      related to previously described phytopathogenic taxa of the genus Acidovorax. DNA
      DNA hybridization studies showed that the lamb's lettuce strains were 91-100%
      related to a representative strain, strain CFBP 4730(T), and constituted a
      discrete DNA hybridization group, indicating that they belong to the same novel
      species. Results from DNA-rRNA hybridization, 16S rRNA sequence analysis and
      fatty acid analysis studies confirmed that this novel species belongs to the beta
      subclass of the Proteobacteria and, more specifically, to the family
      Comamonadaceae and the genus Acidovorax. The name Acidovorax valerianellae sp.
      nov. is proposed for this novel taxon of phytopathogenic bacteria. The type
      strain is strain CFBP 4730(T) (= NCPPB 4283(T)).

PMID- 12807203
TI  - Streptomyces speibonae sp. nov., a novel streptomycete with blue substrate
      mycelium isolated from South African soil.
AB  - An actinomycete with blue substrate mycelium was isolated from a soil sample in
      Cape Town, South Africa, and designated strain PK-Blue(T). The colour of the
      substrate mycelium was not sensitive to changes in pH. The organism produced
      hairy spores in Spirales-type spore chains. Chemical taxonomy indicated that it
      belonged to the genus Streptomyces. Strain PK-Blue(T) produced no diffusible
      pigments other than melanin, grew at 45 degrees C, did not degrade adenine and
      exhibited no antibacterial activity against Enterococcus faecium, Escherichia
      coli or Pseudomonas aeruginosa. Analysis of its 16S rRNA gene sequence and the
      results of physiological tests showed that strain PK-Blue(T) (= DSM 41797(T) =
      ATCC BAA-411(T)) represents the type strain of a novel species of Streptomyces,
      for which the name Streptomyces speibonae sp. nov. is proposed.

PMID- 12807204
TI  - Escherichia albertii sp. nov., a diarrhoeagenic species isolated from stool
      specimens of Bangladeshi children.
AB  - The taxonomic position of a group of five D-sorbitol- and lactose-negative
      enterobacterial isolates recovered from diarrhoeal stools of children at the
      International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), was
      investigated by DNA-DNA hybridization, phenotypic characterization and 16S rDNA
      sequencing. These strains were originally identified as 'Hafnia alvei-like' with
      the API 20E system but, in fact, show more phenotypic and genotypic resemblance
      to members of the genus Escherichia. By 16S rDNA sequencing, one representative
      strain of the ICDDR,B group was shown to be closely affiliated to the genera
      Escherichia and Shigella. Using the fluorimetric microplate hybridization method,
      the diarrhoeagenic ICDDR,B isolates were found to constitute a homogeneous taxon
      (> or = 82% internal DNA relatedness), with the closest affiliation to the type
      strains of Escherichia coli (55-64%) and Shigella flexneri (54-60%). The DNA-DNA
      hybridization levels were much lower with members of other described Escherichia
      species (16-45%) and with the type strain of H. alvei (9-17%). The G + C content
      of the ICDDR,B strains ranged from 50.5 to 50.7 mol%. Together with the
      diagnostic characteristics reported previously, including the presence of the
      eaeA gene of enteropathogenic E. coli and of the E. coli and Shigella-specific
      phoE gene, it is concluded that the ICDDR,B strains represent a novel taxon in
      the genus Escherichia, for which the name Escherichia albertii sp. nov. is
      proposed. Its type strain is Albert 19982(T) (= LMG 20976(T) = CCUG 46494(T)).

PMID- 12807205
TI  - Allofustis seminis gen. nov., sp. nov., a novel Gram-positive, catalase-negative,
      rod-shaped bacterium from pig semen.
AB  - An unknown Gram-positive, catalase-negative, facultatively anaerobic, non-spore
      forming, rod-shaped bacterium originating from semen of a pig was characterized
      using phenotypic, molecular chemical and molecular phylogenetic methods. Chemical
      studies revealed the presence of a directly cross-linked cell wall murein based
      on L-lysine and a DNA G + C content of 39 mol%. Comparative 16S rRNA gene
      sequencing showed that the unidentified rod-shaped organism formed a hitherto
      unknown subline related, albeit loosely, to Alkalibacterium olivapovliticus,
      Alloiococcus otitis, Dolosigranulum pigrum and related organisms, in the low-G +
      C-content Gram-positive bacteria. However, sequence divergence values of > 11%
      from these recognized taxa clearly indicated that the novel bacterium represents
      a separate genus. Based on phenotypic and phylogenetic considerations, it is
      proposed that the unknown bacterium from pig semen be classified as a new genus
      and species, Allofustis seminis gen. nov., sp. nov. The type strain is strain 01
      570-1(T) (= CCUG 45438(T) = CIP 107425(T)).

PMID- 12807206
TI  - Spirochaeta americana sp. nov., a new haloalkaliphilic, obligately anaerobic
      spirochaete isolated from soda Mono Lake in California.
AB  - A novel, obligately anaerobic, mesophilic, haloalkaliphilic spirochaete, strain
      ASpG1(T), was isolated from sediments of the alkaline, hypersaline Mono Lake in
      California, USA. Cells of the Gram-negative strain were motile and spirochaete
      shaped with sizes of 0.2-0.22 x 8-18 microm. Growth of the strain was observed
      between 10 and 44 degrees C (optimum 37 degrees C), in 2-12% (w/v) NaCl (optimum
      3% NaCl) and between pH 8 and 10.5 (optimum pH 9.5). The novel strain was
      strictly alkaliphilic, required high concentrations of carbonates in the medium
      and was capable of utilizing D-glucose, fructose, maltose, sucrose, starch and D
      mannitol. End products of glucose fermentation were H2, acetate, ethanol and
      formate. Strain ASpG(T) was resistant to kanamycin and rifampicin, but sensitive
      to gentamicin, tetracycline and chloramphenicol. The G + C content of its DNA was
      58.5 mol%. DNA-DNA hybridization analysis of strain ASpG1(T) with its most
      closely related species, Spirochaeta alkalica Z-7491(T), revealed a hybridization
      value of only 48.7%. On the basis of its physiological and molecular properties,
      strain ASpG1(T) appears to represent a novel species of the genus Spirochaeta,
      for which the name Spirochaeta americana is proposed (type strain ASpG1(T) =ATCC
      BAA-392(T) = DSM 14872(T)).

PMID- 12807208
TI  - Marinomonas primoryensis sp. nov., a novel psychrophile isolated from coastal sea
      ice in the Sea of Japan.
AB  - Two bacterial strains (KMM 3633(T) and KMM 3634) were isolated from marine
      coastal sea-ice and characterized by using phenotypic and molecular methods. The
      isolates were aerobic, Gram-negative, psychrophilic, halophilic and motile by
      means of a single polar flagellum. The DNA G + C content was 45.3-45.6 mol%. The
      major cellular fatty acids were C(16 :0), C(16 : 1)omega9c and C(18 : 1)omega7c.
      Comparison of almost-complete 16S rDNA sequences demonstrated that the strains
      were phylogenetically closely related to each other (99.5% sequence identity),
      and related to Marinomonas species (94.4-96.4% identity). DNA-DNA reassociation
      between KMM 3633(T) and KMM 3634 occurred at a level of 92%. Based on phenotypic,
      chemotaxonomic and phylogenetic properties, the name Marinomonas primoryensis sp.
      nov. is proposed for strains KMM 3633(T) and KMM 3634; the type strain is KMM
      3633(T) (= JCM 11775(T) = NRIC 523(T)).

PMID- 12807207
TI  - Sulfurihydrogenibium subterraneum gen. nov., sp. nov., from a subsurface hot
      aquifer.
AB  - A polyphasic taxonomic study was performed on a novel facultatively anaerobic,
      hydrogen- or sulfur/thiosulfate-oxidizing, thermophilic chemolithoautotroph
      recently isolated from subsurface hot aquifer water in a Japanese gold mine. The
      cells were straight to slightly curved rods, with a single polar flagellum.
      Growth was observed at 40-70 degrees C (optimum 60-65 degrees C; 80 min doubling
      time) and at pH 6.4-8.8 (optimum pH 7.5). The isolate was unable to use complex
      organic compounds, carbohydrates, amino acids or organic acids as sole energy and
      carbon sources. The G + C content of the genomic DNA was 31.3 mol%. Phylogenetic
      analysis based on 16S rDNA sequences indicated that the isolate was closely
      related to an uncultivated group of micro-organisms within the order Aquificales
      obtained from Icelandic and Japanese hot spring microbial mats, but distantly
      related to previously identified genera of the Aquificales such as Persephonella,
      Aquifex and Hydrogenobacter. The name Sulfurihydrogenibium subterraneum gen.
      nov., sp. nov. is proposed for this novel species; the type strain is HGMK1(T) (=
      JCM 11477(T) = ATCC BAA-562(T) = DSM 15120(T)).

PMID- 12807209
TI  - 'Candidatus phytoplasma phoenicium' sp. nov., a novel phytoplasma associated with
      an emerging lethal disease of almond trees in Lebanon and Iran.
AB  - Almonds (Prunus amygdalus) represent an important crop in most Mediterranean
      countries. A new and devastating disease of almond trees in Lebanon was recently
      reported, characterized by the development of severe witches'-brooms on which no
      flowers or fruits developed, and leading to tree death within a few years. A
      phytoplasma was detected in diseased trees by PCR amplification of rRNA operon
      sequences, and RFLP patterns of amplified DNA indicated that the phytoplasma
      belonged to the pigeon pea witches'-broom (PPWB) group. In the present work, the
      presence of a phytoplasma in symptomatic plants was confirmed by electron
      microscopy; this phytoplasma was graft-transmissible to almond, plum and peach
      seedlings. The phytoplasma was characterized by sequence analysis of rRNA genes
      and was shown to be different from the phytoplasmas previously described in the
      PPWB group. A 16S rDNA phylogenetic tree identified the almond tree phytoplasma
      as a member of a distinct subclade of the class Mollicutes. Oligonucleotides have
      been defined for specific detection of the new phytoplasma. The almond
      phytoplasma from Lebanon was shown to be identical to a phytoplasma that induces
      a disease called 'almond brooming' in Iran, but different from another PPWB-group
      phytoplasma that infects herbaceous annual plants in Lebanon. Based on its unique
      properties, the name 'Candidatus Phytoplasma phoenicium' is proposed for the
      phytoplasma associated with almond witches'-broom in Lebanon and Iran.

PMID- 12807211
TI  - Thermococcus gammatolerans sp. nov., a hyperthermophilic archaeon from a deep-sea
      hydrothermal vent that resists ionizing radiation.
AB  - Enrichments for anaerobic organotrophic hyperthermophiles were performed with
      hydrothermal chimney samples collected at the Guaymas Basin (27 degrees 01' N,
      111 degrees 24' W). Positive enrichments were submitted to gamma-irradiation at a
      dose of 30 kGy. One of the resistant strains, designated strain EJ3(T), formed
      regular motile cocci. The new strain grew between 55 and 95 degrees C, with an
      optimum growth temperature of 88 degrees C. The optimal pH for growth was 6.0,
      and the optimum NaCl concentration for growth was around 20 g l(-1). Strain
      EJ3(T) was an obligately anaerobic heterotroph that utilized yeast extract,
      tryptone and peptone. Elemental sulfur or cystine was required for growth and
      reduced to hydrogen sulfide. The G + C content of the genomic DNA was 51.3 mol%.
      As determined by 16S rRNA gene sequence analysis, the organism was most closely
      related to Thermococcus celer, Thermococcus guaymasensis, Thermococcus
      hydrothermalis, Thermococcus profundus and Thermococcus gorgonarius. However, no
      significant homology was observed between them by DNA-DNA hybridization. The
      novel organism also possessed phenotypic traits that differ from those of its
      closest phylogenetic relatives. Therefore, it is proposed that this isolate,
      which constitutes the most radioresistant hyperthermophilic archaeon known to
      date, should be described as the type strain of a novel species, Thermococcus
      gammatolerans sp. nov. The type strain is EJ3(T) (= DSM 15229(T) = JCM 11827(T)).

PMID- 12807210
TI  - Deferribacter desulfuricans sp. nov., a novel sulfur-, nitrate- and arsenate
      reducing thermophile isolated from a deep-sea hydrothermal vent.
AB  - A novel anaerobic, heterotrophic thermophile was isolated from a deep-sea
      hydrothermal vent chimney at the Suiyo Seamount in the Izu-Bonin Arc, Japan. The
      cells were bent, flexible rods, with a single polar flagellum. Growth was
      observed between 40 and 70 degrees C (optimum temperature: 60-65 degrees C;
      doubling time, 40 min) and between pH 5.0 and 7.5(optimum pH 6.5). The isolate
      was a strictly anaerobic heterotroph capable of using complex organic compounds
      (yeast extract, tryptone, peptone, casein and Casamino acids), ethanol and
      various organic acids as energy and carbon sources. Hydrogen could serve as a
      supplementary energy source. Elemental sulfur (S(0)), nitrate or arsenate was
      required for growth as an electron acceptor. The G + C content of the genomic DNA
      was 38.6 mol%. Phylogenetic analysis based on 16S rDNA sequences indicated that
      isolate SSM1(T) is closely related to Deferribacter thermophilus BMA(T) (98.1%).
      However, the novel isolate could be clearly differentiated from D. thermophilus
      BMA(T) on the basis of its physiological and genetic properties. The name
      Deferribacter desulfuricans sp. nov. (type strain SSM1(T) = JCM 11476(T) = DSM
      14783(T)) is proposed.

PMID- 12807212
TI  - Flavobacterium xinjiangense sp. nov. and Flavobacterium omnivorum sp. nov., novel
      psychrophiles from the China No. 1 glacier.
AB  - Two novel psychrophilic bacterial strains (ZF-6(T) and ZF-8(T)) were isolated
      from the China No. 1 glacier. Polyphasic taxonomy using physiological and
      biochemical properties and phylogenetic analysis based on 18S rRNA gene sequences
      showed that the two isolates belonged to the genus Flavobacterium, and that they
      were distinct from each other and also from the known species of this genus.
      Strains ZF-6(T) and ZF-8(T) are Gram-negative and both have an optimal growth
      temperature of 11 degrees C. Strain ZF-6(T) is able to grow at 0-20 degrees C,
      the G + C content of its genomic DNA is 34.4 mol% and the major fatty acids of ZF
      6(T) are C(16 : 1)omega7c (17.7%) and C15 : 1)omega6c (12.7%). Strain ZF-8(T)
      showed a strong ability to degrade organic macromolecules such as starch, CM
      cellulose, pectin and chitin. Its DNA G + C content is 35.1 mol%, and the major
      fatty acids are C(16 : 1)omega7C (18.2%) and C(15 : 0) (9.9%). Phylogenetic
      analysis based on 16S rDNA sequences indicated that ZF-6(T) and ZF-8(T) belong to
      the genus Flavobacterium and represent two novel species. DNA-DNA hybridization
      also supported the status of the two new isolates. The names Flavobacterium
      xinjiangense sp. nov. (type strain, ZF-6(T) = AS 1.2749(T) = JCM 11314(T)) and
      Flavobacterium omnivorum sp. nov. (type strain, ZF-8(T) = AS 1.2747(T) = JCM
      11313(T)) are proposed for the two new isolates.

PMID- 12807213
TI  - Description of Comamonas aquatica comb. nov. and Comamonas kerstersii sp. nov.
      for two subgroups of Comamonas terrigena and emended description of Comamonas
      terrigena.
AB  - Three clusters of isolates have previously been defined within the species
      Comamonas terrigena, on the basis of DNA-rRNA and DNA-DNA hybridization data, and
      of protein electrophoretic patterns and immunotyping. More detailed
      characterization in the current study shows that representatives of these three
      groups can also be differentiated phenotypically from each other. Strains of C.
      terrigena sensu stricto (C. terrigena DNA group 1) are pyrrolidone aminopeptidase
      positive, do not grow at 40 degrees C, are L-alanine-positive and are always
      negative for 4-hydroxybenzoate. Strains of C. terrigena DNA groups 2 and 3 are
      pyrrolidone aminopeptidase-negative; the former is the only group that is
      tyrosine-negative, and only the latter can grow at 42 degrees C (with an optimal
      growth temperature of 40 degrees C). These findings are corroborated by
      differences in 16S rDNA sequence and tRNA intergenic spacer lengths. Therefore,
      it is proposed to rename C. terrigena DNA group 2 [containing former
      Aquaspirillum aquaticum and E. Falsen (EF) group 10 strains] as Comamonas
      aquatica sp. nov., and C. terrigena DNA group 3 (containing former EF group 10
      strains) as Comamonas kerstersii sp. nov.

PMID- 12807214
TI  - Persephonella hydrogeniphila sp. nov., a novel thermophilic, hydrogen-oxidizing
      bacterium from a deep-sea hydrothermal vent chimney.
AB  - A novel thermophilic, hydrogen-oxidizing bacterium, designated 29W(T), was
      isolated from a deep-sea hydrothermal vent chimney sample collected from the
      Suiyo Seamount in the Izu-Bonin Arc, Japan, at a depth of 1385 m. The cells were
      cocci (0.9-1.0 microm in diameter) and straight rods (2.3-2.7 microm long) under
      static and agitated culture conditions, respectively. The new isolate was an
      obligate chemolithoautotroph growing by respiratory nitrate reduction with H2,
      forming N2 as a final product. A very low concentration of O2 (optimum 0.6-0.8%,
      v/v) was also used as an alternative electron acceptor while reduced sulfur
      compounds did not serve as electron donors. Anoxic hydrogen-oxidizing growth with
      nitrate was observed between 50 and 72.5 degrees C (optimum 70 degrees C; 40 min
      doubling time), pH 5.5 and 7.6 (optimum pH 7.2), and in the presence of 1.5 and
      5.0% NaCl (optimum 2.5%). The G + C content of the genomic DNA was 37.3 mol%.
      Phylogenetic analysis based on 16S rDNA sequences indicated that the isolate was
      a member of the recently described genus Persephonella in a potential new family
      within the order Aquificales. On the basis of the physiological and molecular
      properties of the new isolate, the name Persephonella hydrogeniphila sp. nov. is
      proposed. The type strain is strain 29W(T) (= JCM 11663(T) = DSM 15103(T)).

PMID- 12807215
TI  - Amycolatopsis keratiniphila sp. nov., a novel keratinolytic soil actinomycete
      from Kuwait.
AB  - A keratinolytic, nocardioform actinomycete, strain D2(T), was isolated from
      Kuwait marsh soil by the bait technique using animal wool. Strain D2(T) was an
      aerobic, Gram-positive organism that produced light-grey aerial mycelium but no
      specific spore chains. 16S rDNA sequence analyses and chemotaxonomic markers were
      consistent with the classification of strain D2(T) in the genus Amycolatopsis,
      i.e. it had meso-diaminopimelic acid in its peptidoglycan, arabinose and
      galactose as its diagnostic sugars, the polar lipids phosphatidylinositol,
      phosphatidylethanolamine, hydroxyphosphatidylethanolamine and
      diphosphatidylglycerol, menaquinone MK-9(H4) and an iso-/anteiso-branched fatty
      acid pattern combined with 10-methyl-branched and 2-hydroxy-branched fatty acids.
      Amycolatopsis japonica was the closest phylogenetic neighbour of strain D2(T),
      showing 99.4% 16S rDNA sequence similarity with the novel strain. A. japonica and
      strain D2(T) could be clearly separated from each other on the basis of their low
      DNA-DNA reassociation value (55.9%). These data, together with its distinct
      physiological traits, led to the conclusion that strain D2(T) represented a novel
      species within the genus Amycolatopsis, for which the name Amycolatopsis
      keratiniphila (type strain D2(T) = DSM 44409(T) = NRRL B24117(T)) is proposed.

PMID- 12807216
TI  - Phylogenetic analysis of members of the genus Aeromonas based on gyrB gene
      sequences.
AB  - The phylogenetic relationships of all known species of the genus Aeromonas were
      investigated by using the sequence of gyrB, a gene that encodes the B-subunit of
      DNA gyrase. Nucleotide sequences of gyrB were determined from 53 Aeromonas
      strains, including some new isolates, which were also characterized by analysis
      of the 16S rDNA variable regions. The results support the recognition of the
      family Aeromonadaceae, as distinct from Plesiomonas shigelloides and other
      enteric bacteria. This phylogenetic marker revealed strain groupings that are
      consistent with the taxonomic organization of all Aeromonas species described to
      date. In particular, gyrB results agreed with 16S rDNA analysis; moreover, the
      former showed a higher capacity to differentiate between species. The present
      analysis was useful for the elucidation of reported discrepancies between
      different DNA-DNA hybridization sets. Additionally, due to the sequence diversity
      found at the intraspecies level, gyrB is proposed as a useful target for
      simultaneous identification of species and strains. In conclusion, the gyrB gene
      has proved to be an excellent molecular chronometer for phylogenetic studies of
      the genus Aeromonas.

PMID- 12807217
TI  - Aeromonas hydrophila subsp. ranae subsp. nov., isolated from septicaemic farmed
      frogs in Thailand.
AB  - A group of seven sucrose-negative Aeromonas strains (referred to as group Au)
      isolated from the internal organs of septicaemic farmed frogs (Rana rugulosa) in
      Thailand was subjected to a polyphasic taxonomic study including fluorescent
      amplified fragment length polymorphism (FAFLP) and ERIC-PCR fingerprinting, 16S
      rDNA sequencing, microplate DNA-DNA hybridizations and extensive phenotypic
      characterization. Comparison of FAFLP and ERIC-PCR fingerprints indicated that
      the group Au isolates belonged to the species Aeromonas hydrophila DNA
      hybridization group (HG) 1 in which they represent a genotypic subgroup closely
      affiliated to A. hydrophila subsp. hydrophila and subsp. dhakensis. One
      representative of the Au group exhibited > or = 99.0% 16S rDNA sequence
      similarity with the type strains of the two A. hydrophila subspecies. DNA-DNA
      hybridization with type and reference strains of all known Aeromonas taxa
      revealed that the Au group represented a homogeneous taxon that exhibited the
      highest relatedness with members of the two A. hydrophila subspecies, ranging
      from 75 to 93%. Phenotypic characterization on the basis of 152 features further
      revealed that the Au group isolates differed from A. hydrophila subsp. hydrophila
      or subsp. dhakensis in a total of 13 biochemical properties. Of these,
      assimilation of L-glycine and isobutyrate as sole carbon source, acid production
      from salicin and D-sucrose, and aesculin hydrolysis were of diagnostic value.
      From the results of this study, it can be concluded that the Aeromonas frog
      isolates of the Au group represent a new subspecies of A. hydrophila, for which
      the name Aeromonas hydrophila subsp. ranae subsp. nov. is proposed. Its type
      strain is Au-1D12(T) (=LMG 19707(T) = CCUG 46211(T)).

PMID- 12807218
TI  - Towards a standardized format for the description of a novel species (of an
      established genus): Ochrobactrum gallinifaecis sp. nov.
AB  - A format for the description of single novel species is proposed, which should
      facilitate the reviewing process by assisting the provision of data in a
      standardized form. The abstract must be short and concise, highlighting
      phylogenetic position, morphology and chemotaxonomy for genus affiliation, the
      genotypic and phenotypic basis for species differentiation, and the name and
      deposition numbers from two public culture collections in different countries for
      the type strain: A Gram-negative, rod-shaped, non-spore-forming bacterium (Iso
      196(T)) was isolated from chicken faeces. On the basis of 16S rRNA gene sequence
      similarity, strain Iso 196(T) was shown to belong to the alpha-2 subclass of the
      Proteobacteria related to Ochrobactrum tritici (95.6%), Ochrobactrum grignonense
      (95.0%) and Ochrobactrum anthropi (94.6%), and the phylogenetic distance from any
      validly described species within the genus Brucella was less than 95%.
      Chemotaxonomic data (major ubiquinone - Q-10; major polyamines - spermidine and
      putrescine; major polar lipids - phosphatidylethanolamine, phosphatidylglycerol
      and phosphatidylcholine; major fatty acids - C(18 : 1)omega7c and C(19 : 0) cyclo
      omega8c) supported the affiliation of strain Iso 196(T) to the genus
      Ochrobactrum. The results of DNA-DNA hybridization and physiological and
      biochemical tests allowed genotypic and phenotypic differentiation of strain Iso
      196(T) from the four validly published Ochrobactrum species. Iso 196(T) therefore
      represents a new species, for which the name Ochrobactrum gallinifaecis sp. nov.
      is proposed, with the type strain Iso 196(T) (= DSM 15295(T) = CIP 107753(T)).

PMID- 12807219
TI  - Rhodotorula benthica sp. nov. and Rhodotorula calyptogenae sp. nov., novel yeast
      species from animals collected from the deep-sea floor, and Rhodotorula
      lysiniphila sp. nov., which is related phylogenetically.
AB  - Three novel species of the genus Rhodotorula are described. Rhodotorula benthica
      sp. nov. (type strain JCM 10901(T) = SY-91(T)) and Rhodotorula calyptogenae sp.
      nov. (type strain JCM 10899(T) = SY-86(T)) were respectively isolated from the
      tubeworm Lamellibrachia sp. and the giant white clam Calyptogena sp., collected
      from the deep-sea floor of the Pacific Ocean off Japan. Rhodotorula lysiniphila
      sp. nov. (type strain JCM 5951(T)) is proposed for strains isolated previously in
      Japan and Pakistan. The three species were placed phylogenetically into a species
      complex comprising Rhodotorula laryngis, Rhodotorula minuta, Rhodotorula pallida
      and Rhodotorula slooffiae. R. minuta and R. slooffiae are closely related in both
      the D1/D2 region of the 26S rDNA and the internal transcribed spacer and 5.8S
      rDNA regions. R. benthica and R. laryngis were closer to R. pallida based on the
      D1/D2 region. Other relationships were not clear.

PMID- 12807222
TI  - Strain DSM 6035 is the type strain of Lactobacillus panis (Wiese et al. 1996).
      Opinion 72.
AB  - The Judicial Commission of the International Committee on Systematics of
      Prokaryotes decided that strain DSM 6035 is the type strain of Lactobacillus
      panis with the consequence that the name Lactobacillus panis has been validly
      published.

PMID- 12807221
TI  - Valid publication of the genus name Thermodesulfobacterium and the species names
      Thermodesulfobacterium commune (Zeikus et al. 1983) and Thermodesulfobacterium
      thermophilum (ex Desulfovibrio thermophilus Rozanova and Khudyakova 1974).
      Opinion 71.
AB  - The Judicial Commission of the International Committee on Systematics of
      Prokaryotes decided that the date of valid publication of the genus name
      Thermodesulfobacterium and of the species names Thermodesulfobacterium commune
      and Thermodesulfobacterium thermophilum is 1995. Thermodesulfobacterium mobile
      Rozanova and Pivovarova 1988 is an illegitimate, later synonym of thermophilum.

PMID- 12807220
TI  - Cryptococcus nemorosus sp. nov. and Cryptococcus perniciosus sp. nov., related to
      Papiliotrema Sampaio et al. (Tremellales).
AB  - Three mycocinogenic strains representing the genus Cryptococcus were isolated on
      glucuronate agar from plants and turf collected in the Prioksko-terrasny
      biosphere reserve (Russia). These isolates fit the standard description of
      Cryptococcus laurentii, but differ from its type strain in both their mycocin
      sensitivity profiles and the killing patterns of their mycocins. Sequence
      analyses of the D1/D2 domain of the 26S rDNA and of the internal transcribed
      spacer region confirmed that these isolates represent two novel species, for
      which the names Cryptococcus nemorosus sp. nov. (type strain VKM Y-2906(T)) and
      Cryptococcus perniciosus sp. nov. (type strain VKM Y-2905(T)) are proposed.
      Morphological, physiological and biochemical characteristics, as well as
      mycocinotyping and molecular analysis, show a close affinity between these two
      novel anamorphic species and the teleomorphic species Papiliotrema bandonii
      (Tremellales).

PMID- 12807223
TI  - Paenibacillus durus (Collins et al. 1994, formerly Clostridium durum Smith and
      Cato 1974) has priority over Paenibacillus azotofixans (Seldin et al. 1984).
      Opinion 73.
AB  - The Judicial Commission of the International Committee on Systematics of
      Prokaryotes decided that the name Paenibacillus durus has priority over
      Paenibacillus azotofixans, and that the latter is a later synonym of the former.
      The type strain is therefore strain ATCC 27763 (= DSM 1735).

PMID- 12807224
TI  - Strain NCIMB 13488 may serve as the type strain of Halorubrum trapanicum. Opinion
      74.
AB  - The Judicial Commission of the International Committee on Systematics of
      Prokaryotes decided that strain NCIMB 13488 may serve as the type strain of
      Halorubrum trapanicum.

PMID- 12807225
TI  - Impressions of the IX Conference on Lyme Borreliosis and Other Tick-Borne
      Diseases, August 18-22, 2002.

PMID- 12807227
TI  - Reflections on the FIGO surgical staging of invasive epithelial ovarian cancer.
AB  - The main aims and requirements of any staging system are: to determine the
      anatomical extent of disease, to allow uniform reporting of treatment results,
      comparison of their efficacy and pooling of data from various institutions. It
      should be based on the mode of spread of the neoplasm, take into consideration
      prognostic risk factors and be of prognostic value. A critical review of the FIGO
      staging system for ovarian carcinoma indicates that these aims and requirements
      are not entirely fulfilled. Following are some examples. It does not include
      exact recommendations for comprehensive surgical staging in apparently early
      ovarian cancer and staging is therefore not performed uniformly. The presence of
      parenchymal liver and lung metastasis may be facilitated by modern imaging
      devices. However, according to FIGO rules only simple X-ray procedures are
      allowed preoperatively. The correlation between increasing stage and survival is
      inconsistent and sometimes contrary to that expected. Many known prognostic
      factors are not included in the present staging system. Although the aims of data
      pooling and of uniform reporting of treatment results have been achieved, the
      validity of some comparisons are questionable in view of the variations in
      staging. The intent of this review was not to belittle the major contribution of
      staging to research, understanding and management of ovarian carcinoma, but to
      highlight its deficiencies. New data have accumulated since the FIGO staging
      system of ovarian carcinoma has been adopted and should prompt consideration of
      modifications such as incorporation of modern diagnostic procedures and of some
      established prognostic markers and reshuffling of certain substages.

PMID- 12807226
TI  - Environmental factors and risk for endometrial cancer development.
AB  - Getting to know the most important environmental risk factors for endometrial
      cancer development lets us provide well programmed primary preventive activity,
      thus avoiding or greatly reducing environmental risk factors for diseases. This
      activity may lead to a reduced number of new cases of endometrial cancer. We can
      help women live longer and better by well programmed preventive activity even
      when medical knowledge has reached such a high level of development. The authors
      analysed environmental risk factors for endometrial cancer development based on
      international medical references. The aim of our work was to review the
      environmental risk factors for endometrial cancer development which provoke
      initiation of the disease, sometimes change the clinical stage of the disease and
      influence medical treatment.

PMID- 12807228
TI  - Oncologic and reproductive outcome after fertility-saving surgery in ovarian
      cancer.
AB  - The rate of ovarian tumour diagnosis in reproductive age woman has increased
      parallel to the improvements in diagnostic methods and regular gynaecological
      visits. Because of this organ saving surgical procedures for the preservation of
      reproductive and endocrine functions have gained more interest. Conservative
      surgical approaches for ovarian tumours after surgical staging include
      cystectomy, unilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy
      plus contralateral cystectomy. Ovarian tumours diagnosed in young ages tend to be
      low-stage low-grade malignancies. This not only enables but also necessitates
      preserving the fertility of women who have not completed their family. In
      invasive ovarian cancer, fertility saving surgery is confined to early-stage and
      low-grade disease. But, it also had been reported in advanced stages (up to Stage
      IIIc). Candidates for those procedures were selected according to the FIGO stage,
      grade, ploidy state, histological subtypes and patients' desire. Adjuvant
      chemotherapy is necessary for high-risk patients. The rate of recurrence
      following conservative and radical surgical procedures in low-stage and low-grade
      tumours are 9% and 11.6%, respectively; and disease-free and overall survival
      rates do not differ significantly. Prognosis of borderline ovarian tumours is
      excellent. Five and 20-year survival rates are 95% and 80%, respectively.
      Management of borderline tumours has evolved significantly in the last few
      decades. In contrast to invasive ovarian cancer, borderline tumours can be
      operated on conservatively at all stages. Chemotherapy is rarely prescribed even
      in advanced stages. Eighty percent of malignant germ cell tumours are diagnosed
      less than 30 years of age, and 70-75% of patients have Stage I disease.
      Conservative surgery is generally used in malignant germ cell tumours even in
      advanced stages. The relation between ovulation induction and tumour recurrence
      is not consistent in the literature. Spontaneous pregnancy rates following
      fertility saving surgery has been reported as 60-88%. Because of this over
      treatment of these patients for fertility should be avoided. Briefly, fertility
      saving surgery can be performed safely in germ cell, borderline and early stage
      epithelial ovarian tumours in selected cases. Any increment in the rate of tumour
      recurrence following ovulation induction has not yet been demonstrated. Menstrual
      irregularities caused by chemotherapy are transient. The congenital malformation
      rate of ovarian cancer patients is slightly higher than that of the normal
      population, but no significant difference has been observed between patients who
      received or did not receive chemotherapy.

PMID- 12807229
TI  - Supraclavicular nodal relapse of breast cancer: prevalence, palliation, and
      prognosis.
AB  - PURPOSE: To determine the frequency, palliative effects of radiotherapy (RT) and
      survival of patients developing supraclavicular nodal relapse (SNR) after
      definitive surgery for non-disseminated breast cancer (BCa). METHODS: A
      retrospective study of individuals treated by breast conserving surgery or
      modified radical mastectomy for Stage I to III BCa at a single institution during
      a 17-year period (1980-96) was undertaken. RESULTS: Of the 536 patients studied,
      22 (4%) developed SNR. Among the seven symptomatic women, the complete subjective
      response rate after RT was 71%. Of the 18 evaluable patients with manifest SNRs,
      tumor regression was complete in 12 (66.6%), partial in one (5.6%), and absent in
      five (27.8%). The overall median survival was 11.5 months; five patients (23%)
      survived for at least two years. CONCLUSION: Supraclavicular nodal relapse in
      breast cancer patients occurs infrequently. The application of radiotherapy for
      palliation of SNR was fully justified by the perceived results even though long
      term survival was not often observed.

PMID- 12807230
TI  - Laparoscopic surgery and port-site metastases: routine measurements to reduce the
      risk.
AB  - More and more malignancies are identified by laparoscopy. Concerns have been
      risen about the safety of these procedures, especially after the publications on
      trocar metastases. General laparoscopic techniques should include safety measures
      in order to reduce the risk of implantation metastasis.

PMID- 12807231
TI  - Prognostic value of initial surgical procedure for patients with uterine sarcoma:
      analysis of 123 patients.
AB  - BACKGROUND: The aim of this series was to study the clinical impact of initial
      surgical management, particularly of uterine morcellation. on patients treated
      for uterine sarcoma (US). PATIENTS AND METHODS: Clinical data of 157 patients
      treated for US in our institution were analyzed. Data concerning this initial
      management was available in 123 patients. We consider as "uterine morcellation"
      the following procedures: hysterectomy (vaginal or laparoscopic) with uterine
      "morcellation" described in the surgical report, myomectomy, operative
      hysteroscopy or simple biopsy of the tumor. The clinical outcome considered as
      related to the initial surgical procedure was the rate of pelvic recurrence at
      three months. RESULTS: Of the 123 patients for whom data concerning initial
      surgical management was available, uterine morcellation was performed in 34
      (28%). One-hundred and sixteen patients had a follow-up > or = 3 months after
      surgery. Recurrence was observed in 87 patients. Six had a pelvic recurrence
      within three months following the end of the treatment. The rates of pelvic
      recurrence at three months according or not to uterine morcellation were 3/31
      (8.82%) and 3/79 (3.66%) respectively (p = 0.25). The rates of pelvic recurrences
      at six months were not different in either group (10% versus 10.4%). Overall and
      disease-free survival were similar in both groups. CONCLUSION: In this
      preliminary study, the rates of pelvic recurrence at three months was increased
      in patients who underwent uterine morcellation for US but this difference was not
      statistically significant. A prospective study should be performed in order to
      clarify the prognostic value of initial surgery in patients treated for US and to
      recommend an adequate surgical management for patients in whom the diagnosis of
      uterine sarcoma is suspected before the surgical procedure.

PMID- 12807232
TI  - Parametrial spread is a prognostic factor in endometrial carcinoma.
AB  - OBJECTIVE: Parametrial spread of endometrial carcinoma, including the
      histopathological pattern of the spread and its significance as a prognostic
      factor, as well as its correlation with other prognostic factors are not well
      understood. METHODS: We reviewed histopathologically the resected parametria from
      269 patients with endometrial carcinoma who underwent radical or modified radical
      hysterectomy with pelvic lymphadenectomy. The relationship between parametrial
      spread and other histopathological features, including histological type, tumor
      grade, depth of myometrial invasion, lymph vascular space invasion (LVSI) of the
      myometrium, cervical invasion, adnexal metastasis, lymph node metastasis and
      peritoneal cytology was studied. Clinical outcomes of the patients with
      parametrial spread were also evaluated. RESULTS: Parametrial spread was
      demonstrated in 16 patients (5.9%). Direct invasion of cancer cells to connective
      tissue, LVSI and lymph-node metastasis in the parametrium were seen in 13, seven
      and three cases, respectively. Three patients had all three spread patterns.
      According to the FIGO surgical stage, parametrial spread was found in none of the
      164 patients in Stage I, two (6.3%) of 32 in Stage II, 12 (16.9%) of 71 in Stage
      III, and two (100%) of two in Stage IV. The presence of parametrial involvement
      was significantly correlated with depth of myometrial invasion, cervical
      involvement, lymph-node metastasis, adnexal metastasis. LVSI in the myometrium
      and peritoneal cytology (each, p < 0.01). With a median follow-up of 68.3 months,
      six (37.5%) of 16 patients with parametrial involvement developed recurrence and
      died. CONCLUSION: Direct parametrial extension or lymphatic involvement within
      the parametrium can occur in endometrial carcinoma. Patients with parametrial
      spread have a poor prognosis.

PMID- 12807233
TI  - National guidance on gynaecological cancer management: an audit of gynaecological
      cancer services and management in the South East of England.
AB  - OBJECTIVE: To evaluate the appropriateness of the structure and the process of
      care for gynaecological cancer against national guidelines. SETTING & SAMPLE:
      Incident cases of ovarian and cervical cancer managed between 1 January, 1999 and
      31 December, 2000 in the South East of England. METHODS: Completion of an audit
      form, by a researcher, using the clinical record. Qualitative interviews with
      gynaecologists at each hospital. MAIN OUTCOME MEASURES: Whether hospitals meet
      the requirements for being a 'centre' or a 'unit' for gynaecological cancer and
      whether gynaecologists manage ovarian or cervical cancer according to the
      guidelines. RESULTS: Stage was recorded in the notes of 53% (262/492) of women
      with ovarian cancer but information to assist in determining stage was recorded
      in 86%. Of women who had a stage recorded by the consultant, who should have had
      a laparotomy and be referred for chemotherapy, 81% (169/209) were managed
      according to the guidelines, ignoring whether there was removal of disease to
      nodules of less than 1 cm. Stage was recorded in the notes of 60% (188/315) of
      women with cervical cancer, although information relevant to staging the patient
      was recorded in 66%. Overall 76% (142/188) of women with stage recorded in the
      notes were managed according to the guidelines but 40% (127/315) of women audited
      were not assessable. Only one site met the criteria for being a cancer centre. Of
      the remaining sites, most striking was the inability to assemble a team of
      professionals, including a radiologist, a pathologist and an oncology nurse to
      discuss individual patient care. CONCLUSIONS: Retrospective note audits will be
      hampered by missing data in the clinical record until systems are developed to
      improve the quality of notes. This research suggests that guidelines based on
      FIGO staging for the management of ovarian and cervical cancer are not followed
      and that this may be associated with incomplete cancer management teams.

PMID- 12807234
TI  - Management of pregnancy-associated acute leukemia.
AB  - Since leukocystosis and anemia are common findings in pregnancy, pathological
      alterations in hematopoesis, such as leukemias, can sometimes proceed undetected.
      Chemotherapy during pregnancy carries the risk of teratogenic effects on the
      fetus, and there is little data to guide chemotherapeutic regimens for leukemia
      during pregnancy. The following paper describes our experience in treating two
      women with acute leukemia during pregnancy and the immediate postpartum period,
      and reviews the relevant literature.

PMID- 12807235
TI  - Evaluation of soluble intracellular adhesion molecule-1 (sICAM-1) in benign and
      malignant ovarian masses.
AB  - PURPOSE: To evaluate serum ICAM-1 levels preoperatively in patients with ovarian
      masses. METHODS: Estimation by ELISA assay in 101 women with pelvic tumours and
      16 healthy controls was performed. Correlations of sICAM-1 levels with CA-125,
      Tumour Volume Index, morphological score and pathological findings were studied.
      RESULTS: Fifty-one ovarian tumours were malignant, five were borderline and 45
      benign. Mean levels of sICAM-1 were respectively, 311.1 +/- 182.9 ng/ml, 172.6 +/
      40.1 ng/ml, 241.8 +/- 74.1 ng/ml and 195.6 +/- 68.7 ng/ml for controls. The area
      under ROC curve for sICAM-1 was 0.72 (95% CI 0.58-0.82), the cut-off 250 ng/ml,
      corresponding to 81.3% sensitivity and 52.9% specificity. Serum ICAM-1 correlated
      with morphological score (r = 0.51, p < 0.001), but not with FIGO stage, tumour
      grade, Tumour Volume Index and CA-125. CONCLUSION: sICAM-1 concentrations are
      higher in patients with malignant tumours, but poorly correlate with clinical
      status. The clinical use alone in ovarian malignancy detection and tumour
      differentiation seems to have limited application. Combinations of CA-125 and
      sICAM-1 could improve the test characteristics.

PMID- 12807236
TI  - Effects of tamoxifen on the human female genital tract: review of the literature.
AB  - Tamoxifen is a non-steroidal triphenylethylene derivate, with clear
      antioestrogenic effects on the breast, that is orally administrated for the
      treatment of breast cancer and its prevention in a high-risk population. This
      article analyzes the effects of tamoxifen on the adult human female genital tract
      and considers its carcinogenicity in the gynaecological reproductive organs. It
      has been found that tamoxifen causes oestrogenic changes of the vaginal and
      cervical squammous epithelium and increases the incidence of cervical and
      endometrial polyps. The action of tamoxifen on the human endometrium in
      postmenopausal women is connected with simple oestrogenic effects including
      hyperplasia, while in others with endometrial cystic atrophy. In cases where
      tamoxifen induces endometrial polyps and hyperplasia, the extensive fibrosis
      accounts for difficulties in obtaining endometrial biopsy or resecting the
      polyps. In premenopausal patients tamoxifen disrupts the menstrual cycles and
      causes ovarian cysts, while in postmenopausal patients it induces ovarian cystic
      tumors and endometriomas. Also, postmenopausal patients treated with tamoxifen
      may develop endometriosis, adenomyosis and leiomyomata. In addition, randomized
      trials have shown a link between tamoxifen use in breast cancer patients and the
      development of endometrial carcinomas. Moreover, of note is the fact that the
      association of tamoxifen therapy with uterine mesenchymal neoplasms is higher
      than expected. In conclusion, the most worrying gynaecological side-effect of
      tamoxifen is the well-known increased risk of endometrial carcinomas. Women with
      breast cancer treated with tamoxifen should undergo annual gynaecological
      examination, but endometrial sampling should be obtained only in the event of
      endometrial bleeding.

PMID- 12807237
TI  - Pelvic relapses in ovarian cancer. Role of CA-125, transvaginal ultrasound and
      color Doppler.
AB  - From January 1995 to January 2001, 40 patients with epithelial ovarian cancer
      were treated at our Institution. Fourteen of these, with a clinical CR after
      surgery and platinum-based chemotherapy, were evaluated monthly by gynecological
      examination, Ca-125 RIA assay, pelvic ultrasound with transabdominal and
      transvaginal probe and color Doppler. Six pelvic relapses, from 1.5 to 3.0 cm,
      were detected by transvaginal ultrasound (US). They showed a rich
      neovascularization with low resistance, high flow, PI from 0.3 to 1.0 and RI <
      0.5 in all cases. US did not reveal any sign of relapse in the remaining eight
      patients. In all cases of pelvic relapses ultrasonic signs of recurrence preceded
      the increase of Ca-125 by one to six months (average 3.8).

PMID- 12807238
TI  - Preoperative serum vascular endothelial growth factor (VEGF) in ovarian masses.
AB  - PURPOSE OF THE INVESTIGATION: To determine the diagnostic value of serum vascular
      endothelial growth factor (VEGF) in the preoperative assessment of the nature of
      ovarian masses. MATERIALS AND METHODS: A prospective cohort study was conducted
      from August 2001 to September 2002 on 40 premenopausal and 23 postmenopausal
      patients with ovarian masses. During preoperative workup, patient age, serum Ca
      125 levels, serum VEGF levels, and tumor volume based on ultrasonographic
      examination were determined. Laparoscopic (n=23) or laparotomic (n=39) approaches
      were undertaken to obtain the final pathologic result. According to the final
      ovarian pathology, follicular cysts, corpus luteum cysts and endometriomas were
      grouped as non-neoplastic ovarian masses (n=40, group I). Serous or mucinous
      cyctadenomas, dermoid tumors and fibromas were allocated into the neoplastic
      benign ovarian mass group (n=10, group II). Primary malignant ovarian neoplasms
      were categorized into the neoplastic-malign group (n=12, group III). RESULTS:
      Mean ages of cases among groups I, II and III were 39.0 +/- 2.0, 42.2 +/- 5.2 and
      56.9 +/- 4.2, respectively. As age of the cases enrolled in this sudy increased,
      the more likely was the occurrence of neoplastic malign ovarian pathologies (p <
      0.001). Among postmenopausal cases diagnosed with an ovarian mass, serum Ca-125
      levels were 113.5 +/- 20 IU/ml compared to those in premenopausal cases (85.8 +/-
      16.0, p = 0.05). The values for serum VEGF values among pre- and postmenopausal
      ovarian masses were 46.2 +/- 6.7 pg/ml and 68.2 +/- 7.9, respectively (p = 0.04).
      In group I, serum VEGF levels of endometriomas (56.5 +/- 1.5 pg/ml) were higher
      compared to those of follicular or corpus luteum cysts (30.6 +/- 2.8, p = 0.05).
      In contrast, tumor size appeared to be larger in non-endometriotic. non
      neoplastic cysts (10.1 +/- 2.0 cm), compared to endometriomas (6.4 +/- 0.6 cm, p
      < 0.01). Serum VEGF levels of group III were higher than other groups (p <
      0.001). With respect to the discriminating benign or malign nature of the mass,
      with a specific cut-off value of serum VEGF level of 68.7 pg/ml, the sensitivity,
      specificity, positive and negative likelihood ratios were 92.3%, 88.0%, 3.3 and
      0.1, respectively. For serum Ca-125 levels, the sensitivity, specificity,
      positive and negative likelihood ratio with a statistically relevant cut-off
      value of 102 IU/ml were, 76.9%, 76.0%, 3.21 and 0.3, respectively. Area under
      curve (AUC) for serum VEGF and Ca-125 values were 0.938 (95% CI: 0.81-0.96) and
      0.769 (95% CI: 0.64-0.86), respectively (p = 0.02). Among the postmenopausal
      group, AUC for serum VEGF and Ca-125 was detected as 0.902 (95% CI: 0.70-0.98)
      and 0.873 (95% CI: 0.66-0.91) (p = 0.14). CONCLUSION: Serum VEGF has the
      potential to be considered as a tumor marker with a good diagnostic relevance in
      differentiating the nature of ovarian masses.

PMID- 12807239
TI  - p53 overexpression as a prognostic indicator in endometrial carcinoma.
AB  - PURPOSE: To investigate the prognostic value of p53 overexpression in endometrial
      adenocarcinoma cases of different stages and histologic subtypes. METHODS: One
      hundred and eleven surgically staged endometrial carcinoma (EC) cases from 1996
      to 2000 constituted this retrospective study group. Prognostic factors determined
      through the evaluation of surgery specimens by co-author pathologist, were
      surgical stage, tumor size, histology, histologic and nuclear grade, myometrial
      invasion, adnexal/serosal metastasis, peritoneal cytology, retroperitoneal lymph
      node involvement p53 overexpression was assessed via immunohistochemical
      staining. Tissues that expressed p53 were considered as positive p53 staining. In
      terms of degree of staining, 1-29%, 30-90% and 80-100% of tumoral tissue stained
      with p53 were considered to be mild, moderate and high p53 staining,
      respectively. RESULTS: Mean age and follow-up period of the study group were 58.2
      +/- 10.6 years and 33.4 +/- 2.7 months, respectively. Percentages of cases
      surgically staged as early (I-II) and advanced (III-IV) FIGO stages were 65.8%
      (n: 73) and 34.2% (n: 38), respectively. Cases with positive p53 staining had a
      significantly high mean survival period compared with those with negative p53
      staining (86.6 +/- 6.0 vs 49.1 +/- 8.1, p < 0.001). p53 overexpression was
      statistically detected to be high in Stage III-IV tumors, non-endometrioid
      histologic subtypes (p = 0.019), histologic and nuclear grade 2-3 tumors (p <
      0.001), adnexal/serosal metastasis (p = 0.001), lymph node involvement (p =
      0.012), and positive peritoneal cytology (p = 0.017). The degree of p53 staining
      was remarkably correlated with survival. In cases with mild and high p53
      staining, mean survival times were 47.1 +/- 7.0 months and 57.0 +/- 13.1 months,
      respectively (p = 0.0003) compared to those with high p53 staining. On univariate
      analysis, all of the prognosticators, including p53 staining (p < 0.001) and
      degree of p53 staining (p < 0.001) appeared to be independent risk factors for
      poor prognosis. On multivariate analysis, only pelvic lymph node involvement (p =
      0.03), serosal/adnexal involvement (p = 0.004), and positive peritoneal cytology
      (p = 0.01) were found to be independent prognosticators of survival while p53
      expression (p = 0.743) and degree of p53 staining (p = 0.802) were not detected
      as independent prognosticators. CONCLUSION: p53 overexpression is strongly
      related to poor prognostic indicators in endometrial adenocarcinoma. Although in
      this study p53 overexpression was not detected as an independent prognosticator,
      additional studies with large data set are needed to evaluate the prognostic
      value of p53 expression.

PMID- 12807240
TI  - Accuracy of endometrial biopsy with the Cornier pipelle for diagnosis of
      endometrial cancer and atypical hyperplasia.
AB  - OBJECTIVE: To establish the accuracy of endometrial biopsy with the Cornier
      pipelle in the diagnosis of endometrial cancer and atypical endometrial
      hyperplasia in our milieu. MATERIAL AND METHOD: We reviewed 1,535
      anatomopathologic reports on endometrial biopsies taken from outpatients using
      the Cornier pipelle between 1997 and 2000, in pre- and postmenopausal patients
      with abnormal vaginal bleeding. In 168 patients (10.9%), curettage and/or
      hysterectomy was subsequently carried out. In these cases, the anatomopathologic
      reports were compared to determine sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV) and likelihood ratio (LR). RESULTS:
      Sensitivity was 84.2%, specificity was 99.1%, accuracy was 96.9%, PPV was 94.1%,
      NPV was 93.7% and LR was 93.5. In 249 cases (16.09%) the material was
      insufficient for study. CONCLUSION: We determined that endometrial biopsy taken
      with the Cornier pipelle is, as we practice it, an accurate method for diagnosis
      of endometrial cancer and its precursor, atypical hyperplasia.

PMID- 12807241
TI  - Hyperthermia in gynecologic cancers.
AB  - The opinion from most of the current data is that malignant tumors may be more
      heat sensitive than normal tissues. Hyperthermia has been tested in both
      randomized and non-randomized trials in gynecologic cancers, but has not found a
      place currently, as there is scarce data. As a consequence, adding this tool into
      the conventional methods of cervical cancer and ovarian cancer treatment has not
      been supported. Hyperthermia modifies the effects of not only ionizing radiation
      but also a number of chemotherapeutic agents. The use of hyperthermia in cervical
      cancer is of interest to the radiotherapist, not only because it sensitizes cells
      to the lethal effects of X-rays but even more because hypoxic cells which are
      most resistant to X-rays appear to be most sensitive to hyperthermia. Most of the
      data on the efficacy of intraperitoneal infusion with hyperthermia comes from
      experimental studies or some phase I/II investigations. Since intraperitoneal
      chemotherapy is potentiated by hyperthermia in areas which are at high risk for
      recurrence, further study maybe indicated. The current role for hyperthermia in
      ovarian cancer remains experimental. Additional trials to test the value of
      hyperthermia in patients treated with concurrent chemotherapy and radiation are
      imperative, and good news is expected from the ongoing studies.

PMID- 12807242
TI  - Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early
      course of radiotherapy and prediction of prognosis.
AB  - PURPOSE: To determine whether changes in the Ki-67 index during the early course
      of radiotherapy could predict the prognosis in squamous cell carcinoma of the
      uterine cervix and be of value in clinical practice. MATERIALS AND METHODS:
      Biopsy specimens from 23 cases of histologically confirmed squamous cell
      carcinoma of the cervix were stained with anti-Ki-67 monoclonal antibody prior to
      radiotherapy and after 9 Gy. The correlation between the Ki-67 index, local
      control and distant metastasis was determined by Spearman's correlation test.
      RESULTS: Median age of the patients was 49. According to the FIGO staging system
      four patients had Stage IIA, 16 had Stage IIB, one had Stage IIIA and two had
      Stage IIIB disease. Among the whole group brachytherapy was applied to 17
      patients (17/23) and weekly cisplatin (40 mg/m2) was applied to 15 patients
      (15/23). The mean Ki-67 index prior to radiotherapy and after 9 Gy for the entire
      group were 58.5% and 46.0%, respectively. The Ki-67 index after 9 Gy decreased in
      most of the patients (74%). During a median follow-up of 23 months four patients
      developed local recurrence and four patients developed distant metastasis. No
      significant correlation was detected among the local control and changes in Ki-67
      index after 9 Gy, whereas there was a moderate correlation between distant
      metastasis and changes in Ki-67 index after 9 Gy (r = 0.51, p = 0.01).
      CONCLUSION: The Ki-67 index can be used safely as a proliferation marker in
      cervical carcinomas, and changes in the Ki-67 index during the early course of
      radiotherapy may predict the metastatic potential. However prospective studies
      including a large number of patients with long-term follow-up are necessary to
      confirm the clinical utility of this marker in cervical cancer.

PMID- 12807243
TI  - The value of ultrasonography in preoperative assessment of selected prognostic
      factors in endometrial cancer.
AB  - OBJECTIVE: To determine the efficiency of transabdominal and transvaginal
      ultrasonography (TAS and TVS) in the assessment of myometrial invasion, cervical
      involvement, pelvic lymph nodes, adnexal and omental metastases (preoperative
      staging) of endometrial cancer. METHODS: Transabdominal and transvaginal 2D,
      ultrasound were performed on 90 women to classify myometrial invasion, cervical
      involvement, pelvic lymph nodes and adnexal metastases in endometrial cancer.
      According to this 13 type E (invasion involving the endometrium), 41 type S
      (superficial, of less than 50% of myometrial infiltration), 36 type D (deep
      infiltration) and 22 cervical involvement were identified. There were 15 G1, 60
      G2 and 15 G3 cases. Adnexal, omental and lymph-node metastases were found in 11,
      two and 15 cases, respectively. Endometrial cancer was diagnosed on the basis of
      dilatation and curettage. The degree of invasion was evaluated preoperatively.
      Ultrasonographic findings were compared to surgical staging and histopathology of
      the surgical specimen. RESULTS: The median age of the 90 women was 63.3 +/- 12.3
      years (range 32 to 86 years). The median thickness of malignant endometrium was
      19.5 +/- 9.6 (range 7 to 54 mm). In type E the median thickness was 11.76 +/-
      4.2, in type S 17.3 +/- 7.6, in type D 24.8 +/- 9.8 and in cases with cervical
      involvement 23.2 +/- 11 mm. Myometrial invasion evaluated by TVS was accurate in
      76 of 90 cases (accuracy 84.4%). In type E sensitivity was 92.3%, specificity
      87.0%, positive and negative predictive value, respectively, 63.1% and 98.6%. In
      type S these values were respectively: 78.0%, 93.9%, 91.4%, 80.0% and in type D-
      88.9%, 92.6%, 88.9% and 100.0%. Tumor extension to the cervix was properly
      assessed in 19 of 22 women in which it was present (sensitivity 86.4%,
      specificity 85.3%, positive predictive value 85.5%, negative predictive value
      95.1%). Adnexal metastasis was correctly diagnosed in 8 of 11 cases in which it
      was present (sensitivity 72.7%, specificity 97.5%, positive predictive value 80%,
      negative predictive value 96.3%), and lymph-node metastasis in only 5 of 15 cases
      (sensitivity 33.3%, specificity 100%, positive predictive value 100%, negative
      predictive value 88.2%). CONCLUSION: These results suggest that 2D TAS and TVS
      evaluation of endometrial cancer are reliable methods for preoperative assessment
      of selected prognostic factors, e.g. myometrial invasion, cervical involvement
      and adnexal metastases. However in assessing lymph-node metastases, TVS with its
      low sensitivity, did not provide additional information. Preoperative ultrasound
      examination should be speculated as an important tool in the establishment of
      different surgical choices which can be made after a correct pretreatment
      prognosis.

PMID- 12807244
TI  - Immunohistochemical expression of heat shock protein 27, in normal hyperplastic
      and neoplastic endometrium: correlation with estrogen and progesterone receptor
      status, p53, pRb and proliferation associated indices (PCNA, MIB1).
AB  - Heat shock protein 27 (HSP27) is a relatively small protein produced in response
      to pathophysiological stress. In the current prospective study the presence and
      localization of HSP27 was associated with other potential prognostic factors such
      as: estrogen and progesterone receptors, p53 and proliferative associated indices
      (MIB1, PCNA). One hundred and twenty-two samples of endometrial tissues (65
      endometrial carcinomas, 28 adenomatous hyperplasias, 31 normal endometrium) were
      studied. Patient records were examined for FIGO stage, grade, and depth of
      myometrial invasion, histology and lympho-vascular space invasion. HSPp27
      expression was lower in the group of carcinomas when compared with the cases of
      adenomatous hyperplasias (p < 0.0001), normal proliferative (p < 0.0001) and
      secretory endometrium (p = 0.02). HSP27 expression was higher in carcinomas from
      premenopausal women in comparison with women in menopausal status and
      postmenopausal status. Multivariate tests showed no statistical significance of
      HSP27 expression according to tumor grade and stage. A positive relationship
      between the expression of HSP27 expression and estrogen receptors (p = 0.0018) as
      well as with progesterone receptor (p = 0.0012) was found with linear regression
      analysis of variance. Our data showed that the lower HSP27 expression in
      endometrial carcinomas in comparison with hyperplastic and normal endometrium may
      indicate a decreased endogenous protection mechanism against the various
      stressful stimuli. This expression could be under hormonal control and does not
      seem to be correlated with other conventional or possible prognostic parameters.

PMID- 12807245
TI  - Microvessel density (MVD) as a prognosticator in endometrial carcinoma.
AB  - PURPOSE: To assess microvessel density (MVD) as a marker for angiogenesis in
      endometrial carcinoma (EC) and normal endometrium at the proliferative and
      secretory phase, and to determine its prognostic value on survival among cases
      with EC. METHODS: Forty-three endometrial carcinoma cases were surgically staged
      and recruited for this case-control study. Tissue specimens from hysterectomies
      due to benign conditions (uterine descensus, myoma uteri, chronic pelvic pain,
      adenomyosis), that belonged to proliferative (n = 10) and secretory (n = 10)
      endometrium (n = 10), were studied as the control group (n = 20). MVD was
      assessed in hot areas where a high density of microvessels were detected within
      tumoral tissue and normal endometrium at proliferative and secretory phases.
      Among EC, various prognosticators such as tumor stage, histological and nuclear
      grade, tumor size, lympho-vascular space involvement (LVSI), cervical
      involvement, myometrial invasion, adnexal and lymph node involvement, peritoneal
      cytology and MVD were analysed in regard to survival. RESULTS: The mean age of
      cases with EC was 58.3 +/- 1.4. MVD was apparently high in EC cases (p < 0.05).
      Among control cases, endometrium from proliferative and secretory phases of the
      menstrual cycle was not statistically different (48.5 +/- 3.6 vs 47.4 +/- 3.8,
      respectively). MVD was correlated with high surgical stage (p < 0.001), cervical
      involvement (p = 0.01), adnexal involvement (p = 0.04), lympho-vascular space
      involvement (p = 0.02), pelvic and para-aortic lymph node metastasis (p < 0.001)
      and positive peritoneal cytology (p < 0.001). On univariate analysis, with a MVD
      cut-off value of 81/0.739 mm2, surgical stage (p < 0.001), LVSI (p < 0.001),
      retroperitoneal lymph node involvement (p < 0.001), adnexal metastasis (p <
      0.001), peritoneal cytology (p = 0.005) and MVD count (p < 0.001) appeared to be
      independent factors for survival. On multivariate analysis, only pelvic lymph
      node involvement (p = 0.03) and MVD (p = 0.02) were found to be independent
      prognosticators on survival. CONCLUSIONS: Angiogenesis is apparent in both
      initial and further evolution of a tumoral process. MVD appears to have a
      substantial prognostic value on survival in EC cases.

PMID- 12807246
TI  - Prognostic factors in definitive radiotherapy of uterine cervical cancer.
AB  - PURPOSE: To determine the prognostic factors related to local control and
      survival in 257 patients with uterine cervical cancer treated with definitive
      radiotherapy (RT). MATERIALS AND METHODS: The medical records of 257 patients
      treated with definitive RT from January 1987 to December 1998 were reviewed
      retrospectively. Pretreatment and treatment parameters were analyzed to determine
      their prognostic value onlocal control and survival. Survival analyses were
      performed using the Kaplan-Meier method. The log-rank test was used for
      univariate analyses and the Cox regression model was used for multivariate
      analyses. RESULTS: Median age was 55 (range 25-82). Squamous cell carcinoma was
      the most common histologic type (89.1%). The distribution per FIGO Stage was IIA:
      13.2%; IIB: 54.9%; IIIA: 3.9%; IIIB: 19.8%; IVA: 8.2%. Ninety-eight patients
      (38.1%) were treated with external RT alone; 134 (52.1%) received both external
      RT and intracavitary brachytherapy; 21 (8.2%) received external RT and
      chemotherapy and four (1.6%) received external RT, intracavitary brachytherapy
      and chemotherapy. Median follow-up duration was 50 months (range 24-155 months).
      The failure rate was 51.8% with 26.5% of patients having only local failure,
      16.7% only distant failure and 8.6% both local and distant failure. Five-year
      local progression-free, disease-free and overall survival rates were 58.1%, 44%
      and 63.7%, respectively. In univariate analysis the prognostic factors identified
      for local progression-free survival were histology (p = 0.008), FIGO stage (p <
      0.001), initial hemoglobin (Hgb) level (p = 0.001), total radiation dose (p =
      0.039), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.037) and
      enlarged paraaortic nodes (p = 0.016). In multivariate analysis the prognostic
      factors were FIGO stage (p = 0.014), initial Hgb level (p = 0.040), and use of
      brachytherapy (p = 0.013). The prognostic factors identified for disease-free
      survival were histology (p = 0.011), FIGO stage (p < 0.001), initial Hgb level (p
      < 0.001), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.014) in
      univariate analysis; and FIGO stage (p < 0.001), initial Hgb level (p = 0.017),
      total tumor dose (p = 0.034), use of brachytherapy (p = 0.006) and of
      chemotherapy (p = 0.021) in multivariate analysis. Factors influencing overall
      survival were FIGO stage (p < 0.001), initial Hgb level (p = 0.006), overall
      treatment time (p = 0.028), total tumor dose (p = 0.007), use of brachytherapy (p
      < 0.001), enlarged paraaortic (p < 0.001) and pelvic nodes (p = 0.004) in
      univariate analysis; and FIGO stage (p < 0.001), overall treatment time (p =
      0.031), enlarged paraaortic (p = 0.007) and pelvic lymph nodes (p = 0.043) in
      multivariate analysis. CONCLUSION: Definitive RT is an effective treatment for
      patients with uterine cervical cancer. There are many prognostic factors
      influencing treatment outcome. Brachytherapy and chemotherapy must be added in
      appropriate patients to improve the outcome. Future prospective trials should be
      undertaken to confirm the validity of these factors and to individualize the
      treatment strategy for every patient.

PMID- 12807247
TI  - Frequency of hydatidiform mole in the rural part of Eskisehir: the first
      community-based epidemiological study in Turkey.
AB  - This epidemiological study was performed in order to determine the frequency of
      hydatidiform mole (HM) in the rural part of Eskisehir, Turkey. Four mole cases
      and 6,274 pregnancies were determined in 2,032, women aged 15-49 which was 85% of
      the target population. Mean age, mean marriage age and mean marriage duration of
      the interviewed women were 34.7, 19.1 and 15.6 years, respectively. The frequency
      of HM per 1,000 live births and per 1,000 pregnancies was 0.83 and 0.64,
      respectively. The frequency of HM was lower than the frequencies reported by most
      of the hospital-based studies. We concluded that there appears to be a need to
      conduct properly designed community-based studies with well-established case
      registry systems to find the real incidence of HM in Turkey.

PMID- 12807248
TI  - Vulvar intraepithelial neoplasia (VIN)--diagnostic and therapeutic challenges.
AB  - PURPOSE: Vulvar intraepithelial neoplasia (VIN) represents a current diagnostic
      and therapeutic challenge. The present retrospective study is an institutional
      experience on the diagnosis and management of VIN. METHODS: One hundred and
      thirteen women with VIN were reviewed and analyzed. Diagnosis was established by
      colposcopically directed biopsies whereas treatment was performed by either a
      surgical or a laser CO2 approach. RESULTS: The mean age of all VIN patients was
      47.4 years. The most common symptom was pruritus (60.1%). The majority of the
      lesions were multifocal (N = 64, 56.6%) and located in the non-hairy part of the
      vulva (87.6%). VIN management consisted of laser CO2 treatment in 51 patients
      (45.1%), surgical treatment in 37 (32.7%) whereas 25 VIN, cases were managed by
      conventional medical treatment. The risk of disease relapse was not associated
      with VIN grade (p = 0.35) nor with the treatment modality used (p = 0.42). The
      risk of disease relapse was significantly higher for multifocal lesions (p <
      0.001). Long-term follow-up of our patients showed that four patients (3.5%)
      developed an invasive vulvar carcinoma. CONCLUSION: Our study confirms other
      reports concerning the diagnostic and treatment difficulties of the management of
      VIN. Although the benefits of treatment are obvious there seems to be no
      guarantee that invasion will not occur.

PMID- 12807249
TI  - Efficacy of cisplatin and cyclophosphamide combination for recurrent and
      metastatic carcinoma of the uterine cervix.
AB  - The efficacy of a combination of cyclophosphamide and cisplatin in patients with
      metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients
      were included in the study. Initially, 27 patients (90%) had received pelvic
      radiation and intracavitary boost and one patient was additionally given
      paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by
      cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum
      of six cycles. All patients received a median of four cycles of chemotherapy. The
      overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1,
      PR: 4 patients). Overall response rate and progressive response in patients with
      relapse within the previous radiation field were 9.5% and 66.7%, respectively;
      while for patients who had recurrent disease outside any irradiated area both
      were 44.4%. Eighteen patients (60%) had early withdrawal from the planned
      schedule, which was due to patient incompliance in seven patients (23.3%),
      disease progression in ten (33.3%) and early death after the first cycle in one
      patient (3.3%). Anemia was the most frequent toxicity, necessiating 24
      transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13
      (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one,
      emesis: nine (30.0%) patients. The median survival duration for all eligible
      patients was 11 months. Univariate analysis revealed that progressive response to
      chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p =
      0.003). The combination of cisplatin and cyclophosphamide did not appear to be
      more active than single agent cisplatin in this patient group with a relatively
      poor prognosis. Further studies are required to determine a better therapeutic
      approach for patients with relapsed carcinoma of the cervix.

PMID- 12807250
TI  - Pelvic-paraaortic lymphadenectomy in clinical Stage I endometrial adenocarcinoma:
      a multicenter study.
AB  - PURPOSE: To show the importance of complete surgical pathologic staging of
      clinical Stage I endometrial adenocarcinoma. METHODS: A total of 106 consecutive
      cases of clinical Stage I endometrial adenocarcinomas in two different centers
      were studied. RESULTS: We found an isolated paraaortic invasion in one patient
      without pelvic node invasion (0.94%). There were only three cases of pelvic lymph
      node invasion (2.83%) and three cases of pelvic-paraaortic lymph-node invasion.
      CONCLUSION: We recommend complete lymphadenectom; the real stages of the cases
      can be determined more correctly and excessive treatments can be avoided.

PMID- 12807251
TI  - Preoperative and postoperative correlation of histopathological findings in cases
      of endometrial hyperplasia.
AB  - OBJECTIVES: To determine the preoperative and postoperative correlation of
      histopathological findings in cases of endometrial hyperplasia. MATERIAL AND
      METHODS: One hundred and three patients with endometrial hyperplasia detected by
      surgical curettage performed due to various gynecologic pathologies were treated
      by hysterectomy. We compared retrospectively the histopathological diagnoses
      found on curettage with those found on hysterectomy specimens. The classification
      scheme endorsed by the International Society of Gynecological Pathologists was
      used to classify the endometrial hyperplasia. The histologic findings found on
      the endometrial tissue of curettage specimens were correlated with those from
      hysterectomy specimens. Histopathologic evaluation was performed by a single
      skilled gynecologic pathologist. RESULTS: A total number of 103 women--76 (73.8%)
      premenopausal and 27 (26.2%) postmenopausal--were determined to have endometrial
      hyperplasia on histopathological evaluation of endometrial tissues obtained by
      endometrial curettage performed for evaluation of various bleeding abnormalities.
      These included 94 patients with simple hyperplasia without atypia (91.3%), two
      patients with simple hyperplasia with atypia (1.9%), five patients with complex
      hyperplasia without atypia (4.9%), and two patients with complex hyperplasia with
      atypia (1.9%). Histopathological evaluation of endometrial tissue obtained from
      hysterectomy specimens (of patients diagnosed with hyperplasia on curettage)
      revealed a total number of 65 cases (63.1%) with endometrial hyperplasia, and 38
      cases (36.9%) with various histopathological findings. The correlation between
      preoperative and postoperative endometrial histologic findings was found to be
      statistically insignificant (r = 0.105, p = 0.29). Among 94 patients who were
      found to have simple hyperplasia without atypia on curettage specimens, 55.3%,
      were found to have simple hyperplasia without atypia, 1.1% simple hyperplasia
      with atypia, 5.3% complex hyperplasia without atypia, 9.6% secretory endometrium,
      4.3% proliferative endometrium, 21.3% disorganized proliferative endometrium,
      1.1% corpus luteum persistency, 1.1% basal endometrium, and 1.1% endometrium
      cancer on final hysterectomy specimens. CONCLUSION: Postoperative diagnosis of
      endometrial pathology might be different from that of preoperative especially in
      cases with simple endometrial hyperplasia without atypia.

PMID- 12807252
TI  - Breast cancer metastatic to uterine leiomyosarcoma. A case report and review of
      the literature.
AB  - An unusual case of breast cancer metastatic to leiomyosarcoma of the uterus is
      reported. The patient had multiple metastases from the breast carcinoma and
      presented a pelvic mass in its evolution. A laparotomy with total hysterectomy
      and bilateral oophorectomy was performed to give pain relief. A review of the
      world literature about these uncommon sites of breast metastases is presented.

PMID- 12807253
TI  - Salvage chemotherapy with a combination of irinotecan hydrochloride and mitomycin
      C in platinum- and paclitaxel-resistant epithelial ovarian cancer: case reports.
AB  - INTRODUCTION: The efficacy and toxicity of salvage chemotherapy with a
      combination of irinotecan hydrochloride (CPT-11) and mitomycin C (MMC) for
      platinum-and paclitaxel-resistant epithelial ovarian cancer are reported. CASE
      REPORT: Three consecutive patients with platinum- and paclitaxel- resistant
      epithelial ovarian cancer were treated with 120 mg/m2 of CPT-11 (days 1 and 15)
      and 7 mg/m2 of MMC (days 1 and 15) every four weeks. In all three cases partial
      responses were achieved and overall survivals were 17 months or longer. Most of
      the adverse side-effects were manageable. CONCLUSIONS: This regimen could be
      administered even in heavily pretreated patients with platinum- and paclitaxel-
      resistance. Phase I and II studies are needed to confirm the feasibility of this
      treatment. The efficacy of most salvage treatments for platinum- and paclitaxel
      resistant epithelial ovarian cancer is disappointing, and our cases might be of
      interest from the perspective of treating platinum- and paclitaxel-resistant
      ovarian cancer.

PMID- 12807254
TI  - Assessing the ecological condition of a coastal plain watershed using a
      probabilistic survey design.
AB  - Using a probabilistic survey design, we assessed the ecological condition of the
      Florida (U.S.A.) portion of the Escambia River watershed using selected
      environmental and benthic macroinvertebrate data. Macroinvertebrates were sampled
      at 28 sites during July-August 1996, and 3414 individuals were identified.
      Taxonomic data were distilled into the 8 m of the Stream Condition Index (SCI),
      developed specifically for Florida waterways, and sites were classified on an
      ordinal scale as very good, good, poor, and very poor. The weighted cumulative
      distribution function of the SCI showed that 8% (+/- 7) of the stream and river
      miles in this landscape were in very good condition, while 25% (+/- 7), 51% (+/-
      16), and 16% (+/- 15) were in good, poor, and very poor condition, respectively.
      The only environmental parameter significantly correlated with SCI was dissolved
      oxygen (DO), and two sites classified as very poor had oxygen levels around or
      below 2 mg L(-1). However, other sites exhibited similarly low SCI values without
      the attendant low DO, implying that factors determining site condition were
      complex and multivariate. The results of this survey corroborate Federal and
      state assessments demonstrating that many locations within this watershed exhibit
      significant degradation.

PMID- 12807255
TI  - A longitudinal assessment of the aquatic macroinvertebrate community in the
      channelized lower Missouri River.
AB  - We conducted an aquatic macroinvertebrate assessment in the channelized reach of
      the lower Missouri River, and used statistical analysis of individual metrics and
      multimetric scores to identify community response patterns and evaluate relative
      biological condition. We examined longitudinal site differences that are
      potentially associated with water quality related factors originating from the
      Kansas City metropolitan area, using data from coarse rock substrate in flowing
      water habitats (outside river bends), and depositional mud substrate in slack
      water habitats (dike fields). Three sites above river mile (RM) 369 in Kansas
      City (Nebraska City, RM = 560; St. Joseph, RM = 530; Parkville, RM = 377) and
      three below (Lexington, RM = 319; Glasgow, RM = 228; Hermann, RM = 94) were
      sampled with rock basket artificial substrates, a qualitative kicknet method, and
      the Petite Ponar. We also compared the performance of the methods used. A total
      of 132 aquatic macroinvertebrate taxa were collected from the lower Missouri
      River; one third of these taxa belonged to the sensitive EPOT insect orders
      (Ephemeroptera, Plecoptera, Odonata, and Trichoptera). Rock baskets had the
      highest mean efficiency (34.1%) of the methods, and the largest number of taxa
      was collected by Ponar (n = 69) and kicknet (n = 69) methods. Seven of the 15
      metrics calculated from rock basket data, and five of the nine metrics calculated
      from Ponar data showed highly significant differences (ANOVA, P < 0.001) at one
      or more sites below Kansas City. We observed a substantial reduction in net
      spinning Trichoptera in rock habitats below Kansas City (Lexington), an increase
      in relative dominance of Oligochaeta in depositional habitats at the next site
      downstream (Glasgow), and lower relative condition scores in rock habitat at
      Lexington and depositional habitat at Glasgow. Collectively, these data indicate
      that some urban-related impacts on the aquatic macroinvertebrate community are
      occurring. Our results suggest that the methods and assessment framework we used
      in this study could be successfully applied on a larger scale with concurrent
      water and sediment chemistry to validate metrics, establish impairment levels,
      and develop a specific macroinvertebrate community index for the lower Missouri
      River. We recommend accomplishing this with longitudinal multi-habitat sampling
      at a larger number of sites related to all potential sources of impairment,
      including major tributaries, urban areas, and point sources.

PMID- 12807256
TI  - Confidence intervals of Leq in the case of stationary random noise measurements.
AB  - A common practice in random noise measurements is to assume that the noise
      samples are normally distributed. Since the sound pressure level (Lp) is related
      with the sound energy by a non linear equation, the distribution of the two
      variables will be different. If one assumes that the probability density function
      (pdf) of Lp is normal, the pdf of noise energy is not and vice versa. A simple
      criterion based on statistical properties of sampled noise can be used for the
      determination of the kind of distribution of the measured noise. The case in
      which the noise energy emitted by the source, and the case in which the measured
      noise level is normally distributed are examined. For each case confidence
      intervals of the calculated equivalent level are calculated.

PMID- 12807257
TI  - Monitoring and assessment of daily exposure of roadside workers to traffic noise
      levels in an Asian city: a case study of Bangkok streets.
AB  - Four noise monitoring sites were strategically established to evaluate average
      noise level and audiometric assessment at various traffic zones of Bangkok
      Metropolitan Region (BMR). During the monitoring period, noise levels were found
      to be 72.8-83.0 dBA during day time and 59.5-74.5 dBA during night time. The
      finding also indicated that traffic noise levels depend on distance from
      roadside, diurnal variation and character of the traffic and street
      configuration. Audiometric measurement of 4000 persons was carried by four major
      hospitals in Bangkok to study the relationship between traffic noise exposure of
      groups of people working in the streets and hearing loss. Four different
      categories of occupational people, i.e., drivers, street vendors, traffic
      officers and dwellers were selected and were further classified into age groups
      (16-25, 26-35, 36-45 and 46-55 years old) to monitor the traffic noise induced
      hearing loss throughout their everyday lives. The control group was deliberately
      chosen to screen out the effects of traffic noise. According to the audiometric
      investigation, it was revealed that hearing capacity of the daily noise exposure
      groups living in the three urban sites (Yaowarat Road, Din Daeng Road and
      Ratchaprarop Road) were noticeably poorer than those who were living in suburban
      site (Phahonyothin Road). It was noted that the mean hearing threshold level
      (HTL) of the 16-25 years old groups were found to have better hearing capacity
      than those older adults of 46-55 years old. In particular the mean HTL dropped at
      the frequency of 4000 Hz. Among the occupational population who were living in
      the urban monitoring sites, the driver groups were found to have the highest risk
      of traffic noise induced hearing loss.

PMID- 12807258
TI  - Antibiotic resistance analysis of fecal coliforms to determine fecal pollution
      sources in a mixed-use watershed.
AB  - Antibiotic resistance analysis was performed on fecal coliform (FC) bacteria from
      a mixed-use watershed to determine the source, human or nonhuman, of fecal
      coliform contamination. The study consisted of discriminant analysis of
      antibiotic resistance patterns generated by exposure to four concentrations of
      six antibiotics (ampicillin, gentamicin sulfate, kanamycin, spectinomycin
      dihydrochloride, streptomycin sulfate, and tetracycline hydrochloride). A
      reference database was constructed from 1125 fecal coliform isolates from the
      following sources: humans, domestic animals (cats and dogs), agricultural animals
      (chickens, cattle, and horses), and wild animals. Based on similar antibiotic
      resistance patterns, cat and dog isolates were grouped as domestic animals and
      horse and cattle isolates were grouped as livestock. The resulting average rate
      of correct classification (ARCC) for human and nonhuman isolates was 94%. A total
      of 800 FC isolates taken from the watershed during either a dry event or a wet
      event were classified according to source. Human sources contribute a majority (>
      50%) of the baseflow FC isolates found in the watershed in urbanized areas.
      Chicken and livestock sources are responsible for the majority of the baseflow FC
      isolates found in the rural reaches of the watershed. Stormwater introduces FC
      isolates from domestic (approximately 16%) and wild (approximately 21%) sources
      throughout the watershed and varying amounts (up to 60%) from chicken and
      livestock sources. These results suggest that antibiotic resistance patterns of
      FC may be used to determine sources of fecal contamination and aid in the
      direction of water quality improvement.

PMID- 12807259
TI  - Distribution of airborne particles from multi-emission source.
AB  - The purpose of this work was to study the distribution of airborne particles in
      the surroundings of an iron and steel factory in southern Finland. Several
      sources of particulate emissions are lying side by side, causing heavy dust
      loading to the environment. This complicated multi-pollutant situation was
      studied mainly by SEM/EDX methodology. Particles accumulated on Scots pine bark
      were identified and quantitatively measured according to their element content,
      size and shape. As a result, distribution maps of particulate elements were drawn
      and the amount of different particle types along the study lines was plotted.
      Particulate emissions from the industrial or energy production processes were not
      the main dust source. Most emissions were produced from the clinker crusher.
      Numerous stockpiles of the industrial wastes and raw materials also gave rise to
      particulate emissions as a result of wind erosion. It was concluded that SEM/EDX
      methodology is a useful tool for studying the distribution of particulate
      pollutants.

PMID- 12807260
TI  - Identification and leaching characteristics of sludge generated from metal
      pickling and electroplating industries by Toxicity Characteristics Leaching
      Procedure (TCLP).
AB  - One of India's major concerns is the increasing level of land pollution largely
      due to the uncontrolled disposal of industrial solid and hazardous waste. With
      rapid industrialization, the generation of industrial solid and hazardous waste
      has increased appreciably and the nature of waste generated has become complex.
      Their impacts on the ecological bodies are noticeable. The article describes the
      details of studies conducted using Toxicity Characteristics Leaching Procedure,
      to estimate the toxicity effects of the metals viz., chromium, zinc, manganese,
      iron, nickel, cobalt and copper by the Zero Headspace Extractor for the sludges
      generated from effluent treatment plant of steel tube, wire and plating
      industries on environment constituents like groundwater, surface water and land.
      Toxicity Characteristics Leaching Procedure determines the mobility of organic
      and inorganic analytes of liquid, solid or multiphase waste from hazardous solid
      wastes in the form of primary and secondary extracts. These extracts are mixed in
      equal volume proportion and analyzed by Direct Reading 2000 spectrophotometer.
      The amount of heavy metals observed during the studies in the leachates were
      found and the results were compared with Hazardous Waste categories as per Indian
      Standards. TCLP regulatory limits given by United States Environment Protection
      Agency (USEPA) and Germany Leachate Quality Standards and it was observed that
      they were on higher side, needing a proper preventive concept of sludge
      management including handling, treatment, recovery and disposal.

PMID- 12807261
TI  - Assessment of community noise problem in Greater Beirut Area, Lebanon.
AB  - Over the last two decades, urban noise has been increasing rapidly, primarily in
      urban areas, due to population growth and the increase of certain noise sources.
      The main objective of this paper is to assess the sources and possible impacts of
      the community noise problems in Lebanese urban areas, particularly the Greater
      Beirut Area. The causes and effects of community noise pollution are briefly
      presented. Sound pressure levels that were measured to define existing noise
      exposure levels in various locations in the Greater Beirut Area are also
      presented. The attitudes toward noise pollution and perceived annoyance impact on
      a sample of 1,038 exposed residents are described. The association between
      measured noise levels and sources, as well as annoyance, is examined using
      correlation analysis and linear and multiple linear regressions. A set of
      recommendations is presented to reduce community noise problem in Greater Beirut
      Area.

PMID- 12807262
TI  - Using environmental stressor information to predict the ecological status of
      Maryland non-tidal streams as measured by biological indicators.
AB  - In Maryland. U.S., an interim framework has recently been developed for using
      biologically based thresholds, or 'biocriteria', to assess the health of nontidal
      streams statewide at watershed scales. The evaluation of impairment is based on
      indices of biological integrity from the Maryland Biological Stream Survey
      (MBSS). We applied logistic regression to quantify how the biotic integrity of
      streams at a local scale is affected by cumulative effects resulting from
      catchment land uses, point sources, and nearby transmission line rights-of-way.
      Indicators for land use were developed from the remote sensing National Land
      Cover Data and applied at different scales. We determined that the risk of local
      impairment in nontidal streams rapidly increases with increased urban land use in
      the catchment area. The average likelihood of failing biocriteria doubled with
      every 10% points increment in urban land, thus an increase in urban land use from
      0 to 20% quadruples the risk of impairment. For the basins evaluated in this
      study, catchments with more than 40-50% urban land use had greater than 80%
      probability of failing biocriteria, on average. Inclusion of rights-of-way and
      point sources in the model did not significantly improve the fit for this data
      set, most likely because of their low numbers. The overall results indicate that
      our predictive modeling approach can help pinpoint stream ecosystems experiencing
      or vulnerable to degradation.

PMID- 12807263
TI  - Comparison of ordinary and lognormal kriging on skewed data of total cadmium in
      forest soils of Sweden.
AB  - Spatial statistical analysis of georeferenced data of total cadmium (TCd) in
      forest soils of Sweden was assumed to provide more advantageous maps than
      traditional interpolated maps. However, 264 measurements of TCd in O-horizon of
      forest soils displayed skewed frequency distribution. Since atypical observations
      affect badly the variogram, outliers were identified, different data
      transformations were tested and ordinary (OK) and lognormal kriging (LK)
      scenarios were compared based on cross-validation. Results were compared using
      overall measures of predictors, e.g. traditional mean squared prediction error
      (MSPE), mean of kriging variances, variance ratio, median of internally
      standardised residuals, and assessments of classification accuracy, such as
      percentage of correctly predicted samples and within-class MSPE. One outlier was
      identified based on the absolute value of skewness of value differences less or
      equal to one in data pairs separated at certain lag classes. Mapping categories
      characterised by percentage of correct classification and within-class MSPE were
      found to be essential in comparison of kriging results additionally to the
      overall measures. In comparison of kriging methods, OK predicted high values more
      accurately and LK was more effective to predict low and medium values. Thus, OK
      was suggested for mapping high concentration of TCd and other pollutants.
      Percentage of correctly predicted samples and within-class MSPE were found to be
      dependent on kriging method, as well as on the number and limits of categories.

PMID- 12807264
TI  - On the horizontal homogeneity of mass-related aerosol properties.
AB  - We studied the mass-related aerosol properties, simultaneously at two sites at
      the urban roof top level in the same city. No systematic influence of the wind
      vector on the difference in the aerosol concentrations between the two locations
      could be found. These results are compared with results from a second, similar
      experiment over a larger distance including one urban and one rural site.
      Surprisingly, we could not detect a tendency which would indicate that sampling
      air at distance in the order of 1 km would be less affected by the heterogeneity
      than sampling distanced in the order of 10 km apart. On the contrary, the results
      suggest that mass-related properties at two sites in the same city are not
      necessarily more similar than at an urban and a rural site outside the city.
      These results stress the limited horizontal homogeneity of urban atmospheric
      aerosol. As a conclusion it is suggested that single-site measurements of mass
      related aerosol properties should be considered to be representative for an area
      smaller than 1 km2 on size.

PMID- 12807265
TI  - Biomagnification factors (fish to Osprey eggs from Willamette River, Oregon,
      U.S.A.) for PCDDs, PCDFs, PCBs and OC pesticides.
AB  - A migratory population of 78 pairs of Osprey (Pandion haliaetus) nesting along
      the Willamette River in western Oregon was studied in 1993. The study was
      designed to determine contaminant concentrations in eggs, contaminant
      concentrations in fish species predominant in the Ospreys diet, and
      Biomagnification Factors (BMFs) of contaminants from fish species eaten to Osprey
      eggs. Ten Osprey eggs and 25 composite samples of fish (3 species) were used to
      evaluate organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs),
      polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans
      (PCDFs). Mercury was also analyzed in fish. Geometric mean residues in Osprey
      eggs were judged low, e.g., DDE 2.3 microg g(-1) wet weight (ww), sigma PCBs 0.69
      microg g(-1), 2,3,7,8-TCDD 2.3 ng kg(-1), and generally well below known
      threshold values for adverse effects on productivity, and the population was
      increasing. Osprey egg residue data presented by River Mile (RM) are discussed,
      e.g., higher PCDDs were generally found immediately downstream of paper mills and
      eggs from the Willamette River had significantly elevated PCBs and PCDDs compared
      to reference eggs collected nearby in the Cascade Mountains. Prey remains at nest
      sites indicated that the Largescale Sucker (Catostomus macrocheilus) and Northern
      Pikeminnow (Ptychocheilus oregonensis) accounted for an estimated 90.1% of the
      biomass in the Osprey diet, and composite samples of these two species were
      collected from different sampling sites throughout the study area for contaminant
      analyses. With the large percentage of the fish biomass in the Osprey diet
      sampled for contaminants (and fish eaten by Ospreys similar in size to those
      chemically analyzed), and fish contaminant concentrations weighted by biomass
      intake, a mean BMF was estimated from fish to Osprey eggs for the large series of
      contaminants. BMFs ranged from no biomagnification (0.42) for 2,3,7,8-TCDF to 174
      for OCDD. Our findings for the migratory Osprey were compared to BMFs for the
      resident Herring Gull (Larus argentatus), and differences are discussed. We
      believe a BMF approach provides some basic understanding of relationships between
      contaminant burdens in prey species of fish-eating birds and contaminants
      incorporated into their eggs, and may prove useful in understanding sources of
      contaminants in migratory species although additional studies are needed.

PMID- 12807266
TI  - Regulation of veterinary antibiotics in Australia.
AB  - The Australian Pesticides and Veterinary Medicines Authority (APVMA)* registers
      veterinary antibiotic products before they can be supplied, distributed or sold
      in Australia. Extensive scientific assessment on all new veterinary antibiotic
      products is undertaken for the APVMA by experts in other government agencies
      including the Therapeutic Goods Administration (toxicology), the National
      Occupational Health and Safety Commission (occupational health and safety),
      Environment Australia (environmental hazards) and state departments of
      agriculture or primary industry (efficacy and safety) as well as APVMA
      assessments on food residues, trade and manufacturing. The National Health and
      Medical Research Council Expert Advisory Group on Antimicrobial Resistance
      provides advice to the APVMA on the potential transfer of antibiotic resistance
      from the use of antibiotics in animals to humans, and the impact transfer may
      have on public health. Food Standards Australia New Zealand (previously Australia
      New Zealand Food Authority) set maximum residue levels for human foods. The APVMA
      monitors registered product use through compliance activities and an adverse
      experience reporting program, and reviews registered products as necessary. The
      import, manufacture, supply and use of veterinary antibiotics are regulated by
      Commonwealth and State governments in Australia.

PMID- 12807267
TI  - Improving antibiotic use: 25 years of antibiotic guidelines and related
      initiatives.
AB  - In the late 1970s concern in Melbourne teaching hospitals over the increasing
      incidence of antibiotic-resistant microorganisms and inappropriate antibiotic
      prescribing, led to the establishment of a working party to produce guidelines on
      appropriate antimicrobial therapy. Therapeutic Guidelines: Antibiotic is now
      produced, marketed and sold by Therapeutic Guidelines Limited, an independent,
      not-for-profit enterprise that distils best-practice prescribing guidelines for
      Australian health professionals. Therapeutic Guidelines now cover all major
      therapeutic areas. Mere distribution of the guidelines had little impact on
      prescribing habits. However, targeted education campaigns have helped to improve
      antibiotic prescribing. The Antibiotic title remains the flagship of Therapeutic
      Guidelines Limited with sales, surveys and endorsements over 11 editions
      attesting to its wide acceptance and use. Therapeutic Guidelines: Antibiotic is
      one of many initiatives that have contributed to improving antibiotic use and it
      serves as a valuable foundation on which to build other strategies. There is
      demand for a consumer friendly version of the guidelines. In addition, the
      increasing use of computerised prescribing programs has highlighted the need for
      electronic guidelines to be closely integrated with decision support software.

PMID- 12807268
TI  - Active promotion of antibiotic guidelines: an intensive program.
AB  - John Hunter Hospital, a 600 bed tertiary referral centre, has an antimicrobial
      working party comprising representatives from pharmacy, microbiology and
      infectious diseases areas, which is responsible for the development,
      implementation and evaluation of guidelines for the appropriate use of
      antimicrobials. Activities include the development and promotion of a restricted
      antimicrobial policy, and specific guidelines for the management of pneumonia,
      and surgical prophylaxis and wound infection. These guidelines are available on
      the hospital intranet, in hard copies in all wards, and on laminated cards (10 x
      6.5 cm) attached to the hospital identification tag. Active promotion of the
      guidelines is undertaken at orientation and via a 2 week intensive period four
      times per year (corresponding with the registrar rotation), weekly meetings and
      follow up of non-compliance courses directly with the attending medical officer.
      Education and feedback to specific groups is provided as required. Other projects
      include a campaign to encourage oral antibiotics where indicated. Regular drug
      utilisation evaluations are undertaken to measure outcomes, along with other
      indicators of antibiotic use such as the prevalence of antimicrobial resistance.
      Appropriate prescribing of third generation cephalosporins has increased from 21
      per cent to 52 per cent (p = 0.008) of courses between December 1999 and June
      2001.

PMID- 12807269
TI  - State-wide surveillance of in-hospital antimicrobial utilisation in South
      Australia.
AB  - In late 2001, a group of South Australian metropolitan public and private
      hospitals commenced voluntary contribution of data on in-hospital utilisation of
      antimicrobials to the Communicable Disease Control Branch of the Department of
      Human Services. Where possible, hospitals contributed data on all antimicrobials
      dispensed for use within the institution each month. These data were stratified
      into antimicrobials issued to intensive care units and antimicrobials issued to
      all other areas within the hospital. In the first instance, only data relating to
      four antimicrobial classes have been analysed. These classes are third or fourth
      generation cephalosporins, carbapenems, glycopeptides and fluoroquinolones.
      Utilisation of these four classes was presented as a monthly utilisation rate
      i.e., total defined daily doses for each antimicrobial class per month per 1,000
      occupied bed days. These utilisation rates were calculated for each individual
      hospital and for the combined group of contributing hospitals (state-wide rate).
      Although limited data are currently available, results to date demonstrate a much
      higher antimicrobial usage rate in intensive care units than other in-patient
      areas for the classes currently analysed. Considerable variation in the usage of
      various antimicrobials has been noted for individual hospitals, and analysis of
      trends over a longer time period, in conjunction with resistance surveillance
      data, will be required.

PMID- 12807270
TI  - Restriction of third generation cephalosporin use reduces the incidence of
      Clostridium difficile-associated diarrhoea in hospitalised patients.
AB  - Third generation cephalosporin antibiotics (3GC) have become the antibiotics of
      choice in many hospitals in recent years for the treatment of infections such as
      community-acquired pneumonia. However, increased use of 3GCs has also been
      associated with a rise in the occurrence of antibiotic-associated diarrhoea due
      to Clostridium difficile, as well as an increase in the prevalence of antibiotic
      resistant organisms such as methicillin resistant Staphylococcus aureus,
      vancomycin resistant entrococci, and extended-spectrum beta-lactamase-producing
      gram negative bacilli. In Western Australia, greater use of 3GCs was shown to
      correlate with more Clostridium difficile-associated diarrhoea (CDAD) in a large
      acute care teaching hospital during the 1980s. During the 1990s, the use of 3GCs
      in this hospital remained high and, at the end of 1998, a policy was introduced
      to prevent the use of ceftriaxone (the only 3GC in use) without prior approval.
      This resulted in a decline in 3GC use and a 50 per cent reduction in the
      incidence of CDAD during 1999 and 2000. To strengthen these observations, the
      impact of the 3GC policy on the occurrence of CDAD was analysed using time-series
      intervention analysis that showed a statistically significant decrease in the
      occurrence of CDAD during the post-intervention period after controlling for
      exogenous factors. Thus, changes in antibiotic prescribing practices can
      influence the incidence of CDAD and, potentially, antibiotic resistant pathogens.

PMID- 12807271
TI  - Changing GPs' antibiotic prescribing: a randomised controlled trial.
AB  - A randomised controlled trial involving 54 general practitioners (GPs) was
      conducted in Canberra, Australian Capital Territory from September 1997 to
      November 1999. In the first year of the study, 24 GPs, who constituted the active
      arm of the intervention group, were involved in the consideration of evidence and
      the development and implementation of a set of clinical guidelines for the
      treatment of acute respiratory infections. These guidelines were then endorsed in
      a meeting together with specialist colleagues. In the second year of the study
      the group of GPs who had been acting as controls, received a moderate
      intervention consisting of a brief educational event and distribution of the
      locally developed guidelines. We obtained data from January 1997 to December 1999
      from the Health Insurance Commission on prescribing rates for 40 of the doctors
      in the study. The rate of prescribing was calculated as the number of antibiotic
      prescriptions per 100 Medicare services. The average yearly prescribing decreased
      significantly in the intensive intervention group and increased in the moderate
      intervention group, (p=0.026). A mixed effects longitudinal time series model was
      fitted to the data to account for seasonal variation of antibiotic prescribing
      and trends over time. The intensive intervention group significantly reduced
      their antibiotic prescribing over time compared to the moderate intervention
      group, (p<0.001). This study has shown that an intensive intervention in which
      general practitioners were actively engaged in development and consideration of
      the evidence base for the guidelines resulted in a significant fall in general
      antibiotic prescribing.

PMID- 12807272
TI  - Antibiotic prescribing for upper respiratory-tract infections in primary care.
AB  - The use and overuse of antibiotics in humans is a major contributor to the
      selection of antibiotic resistance organisms. Recent evidence has shown that
      primary care prescribing selects for resistances of clinical importance. The
      National Prescribing Service runs both educational and audit activities. The
      latter provide some insight into general practice attitudes toward antibiotic
      prescribing.

PMID- 12807273
TI  - Consumer activities on antimicrobial resistance in Australia.
AB  - The focus of this article is the role of consumer education campaigns in
      Australia and overseas as an important step in helping people develop a more
      considered use of antibiotics. Evidence of the success of campaigns in Australia,
      New Zealand and the United Kingdom is presented. On the basis of this evidence,
      the paper argues that education campaigns are central to reducing inappropriate
      antibiotic use and lowering the chances of antibiotic resistance building up in
      the populations of developed countries.

PMID- 12807274
TI  - Fifteen years of surveillance by the Australian Group for Antimicrobial
      Resistance (AGAR).
AB  - The Australian Group for Antimicrobial Resistance (AGAR) has played a unique role
      in surveillance of antimicrobial resistance in Australia. It has a broad
      laboratory membership representing the major teaching hospitals in all Australian
      capitals and more recently major private pathology laboratories in most states.
      The use of an active surveillance strategy with standard methodology for
      collection and examination of clinically significant isolates has produced data
      accurately reflecting the changing prevalence of antimicrobial resistance in
      major hospitals as well as the community. AGAR has documented the spread of
      methicillin-resistant Staphylococcus aureus in Australian hospitals in the late
      1980s and throughout the 1990s. Surveys of antimicrobial resistance in
      enterococci have monitored the emergence of vancomycin-resistant enterococci as
      an important nosocomial pathogen in Australia. AGAR has also conducted major
      national surveys of resistance in Streptococcus pneumoniae, community isolates of
      Staphylococcus aureus, Haemophilus influenzae and in the Enterobacteriaceae.
      These and other activities have given AGAR a unique perspective on emerging
      patterns of resistance in key pathogens in Australia. The recent extension of
      membership to include more private pathology laboratories may provide the
      opportunity to conduct more representative community based surveys.

PMID- 12807275
TI  - Australian hospital morbidity data on antibiotic resistance.
AB  - Reports of infections with drug-resistant microorganisms are included in the
      National Hospital Morbidity Database (NHMD) at the Australian Institute of Health
      and Welfare. This database includes data on diagnoses of patients admitted to
      Australian hospitals, recorded using codes from the Australian version of the
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM), and the International Statistical Classification of Diseases and
      Related Health Problems, 10th Revision, Australian Modification. Reports of
      infections with drug-resistant microorganisms, recorded as either the patient's
      principal diagnosis, or as a co-morbidity or complication, increased markedly
      between 1994-95 (when the first reports were included) and 2000-01. Infections
      resistant to penicillins were the most commonly recorded. The national
      introduction of the Australian versions of ICD-9-CM in 1995, and of casemix-based
      funding and management from the mid-1990s, has possibly led to more accurate
      medical record documentation and improved coding of these infections and are
      likely explanations for the observed increase in reporting. The NHMD should be
      considered as a component of a national surveillance system for antibiotic
      resistance. Its routine data collection covers almost all hospital separations in
      Australia and is supported by a comprehensive national data collection
      infrastructure.

PMID- 12807276
TI  - SENTRY Antimicrobial Surveillance Program Asia-Pacific region and South Africa.
AB  - The SENTRY Antimicrobial Surveillance Program was initiated in January 1997 and
      was designed to monitor the predominant pathogens and antimicrobial resistance
      for both nosocomial and community-acquired infections globally by using
      validated, reference-quality identification and susceptibility testing methods
      performed in a central laboratory. Consecutive bacterial or fungal isolates,
      deemed clinically significant by local criteria, are forwarded to the local
      reference laboratory from various study objectives. The major objectives include
      blood stream infections, community-acquired respiratory tract infections
      (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis),
      pneumonias in hospitalised patients, skin and soft tissue infections, and urinary
      tract isolates from hospitalised patients. In 2001, special objectives were
      introduced to examine gastroenteritis pathogens and beta-haemolytic streptococcal
      isolates. Over 22 nations participate in SENTRY surveillance globally. The
      Women's and Children's Hospital, Adelaide has been the reference centre for the
      Asia-Pacific region and South Africa since 1998, and three other Australian
      institutions, from Brisbane, Perth, and Adelaide, are part of the global network.
      All isolates received from our region are tested against up to 29 antimicrobial
      agents using custom-made broth microdilution panels. The data generated from
      SENTRY allows Australia to compare our antimicrobial resistance patterns and
      trends with our regional neighbours.

PMID- 12807277
TI  - TSN Database Australia, a new tool to monitor antimicrobial resistance in
      Australia.
AB  - An electronic network of Australian microbiology laboratories was established to
      monitor the emergence and occurrence of antimicrobial resistance among clinically
      relevant bacteria. It is believed that the data network collected approximately
      42 per cent of all antibacterial susceptibility test results generated by
      Australian laboratories. The network comprised 94 hospitals and 9 private
      commercial laboratories. Selected data elements were extracted and electronically
      transmitted to a central location. Upon receipt, all data were first normalised
      and thereafter examined for errors. Duplicate results for the same patient were
      identified to prevent skewing of the data toward resistance. All data passing
      quality assessment was staged for release of a new database release that occurred
      monthly. Unusual test results were first validated prior to their inclusion into
      the database. Using an Internet-based query tool, individual institutions could
      query their own data, but could only query aggregated data for other regional or
      national analyses. Individual patient results could be examined nor could the
      results of any individual institution other than their own. As of March 2002, TSN
      Database Australia contained 14,648,752 test results, from 2,000,394 strains (453
      different taxa) and 1,213,605 patients. Since the same database concept has been
      established in 10 other countries (United States of America, Europe, and Canada),
      observations made in Australia may be compared to those observed elsewhere in the
      world. This article will describe TSN in greater detail, describe the query tool
      and some of the analyses that are possible.

PMID- 12807278
TI  - Monitoring antimicrobial resistance for public health action.
AB  - Antibiotics are used both to treat infections in individual patients and in
      public health interventions to control disease outbreaks. In both circumstances
      the outcome, as measured by morbidity and mortality, is compromised by
      antimicrobial resistance (AMR) in the causative organism. Of necessity,
      antibiotics are frequently given empirically and their selection is based on
      presumptions of efficacy and the susceptibility of the infecting agent. AMR
      surveillance provides reassurance with regard to efficacy and guides the
      formulation of standard treatment regimens. However, AMR surveillance is not
      always appropriately performed nor are the data generated necessarily used to
      best advantage. Optimal use of AMR surveillance data requires for each disease of
      importance: an understanding of the applications of AMR surveillance and a clear
      definition of the type of data required: the 'triggers for surveillance';
      construction of AMR surveillance programs appropriate to differing requirements;
      and better linkages between AMR surveillance data and disease control functions
      so that the thresholds for initiating public health action are clearly defined.
      Examples which illustrate the application of these principles are provided from
      experience with surveillance of AMR in the pathogenic Neisseria (N. gonorrhoeae
      and N. meningitidis).

PMID- 12807279
TI  - Ciprofloxacin resistance emerges in Neisseria gonorrhoeae in Victoria, 1998 to
      2001.
AB  - Notifications of gonorrhoea in Victoria increased suddenly in the late 1990s,
      from an average of 375 cases per year from 1993 to 1997, to over 700 cases in
      2000. This paper describes the susceptibility to ciprofloxacin of isolates of N.
      gonorrhoeae in Victoria from 1998 to 2001, and relates these to the reported
      epidemiologic characteristics of the cases. The proportion of all isolates of N.
      gonorrhoeae that was resistant to ciprofloxacin rose from 3 per cent in 1998 to
      11 per cent in 2001. Among homosexual and bisexual men, resistant isolates
      remained rare (< 1 per cent). Among heterosexual men and women whose infection
      was acquired overseas, the proportion of resistant isolates increased from 14 per
      cent to 51 per cent. Among heterosexual men and women whose infection was
      acquired in Australia, the proportion of resistant isolates increased from 6 per
      cent to 14 per cent, and disproportionately involved persons born overseas.
      Patterns of antibiotic resistance are intimately linked to epidemiological
      characteristics of cases. Clinical treatment and public health and control
      strategies for resurgent sexually transmitted infections benefit from the
      insights of collaborative microbiological and epidemiological surveillance.

PMID- 12807280
TI  - Antibiotic resistance in Campylobacter jejuni isolated from humans in the Hunter
      Region, New South Wales.
AB  - Campylobacter is a common cause of bacterial gastroenteritis in Australia.
      Antibiotic resistance among Campylobacter is an emerging problem in Europe and
      the United States of America. Monitoring may detect emerging resistance. Since
      there is no epidemiologically validated subtyping system for Campylobacter,
      antimicrobial resistance patterns may prove useful as an epidemiological marker.
      Campylobacter isolates from residents of the Hunter region were differentiated by
      PCR into two categories: C. jejuni and non-C. jejuni. Minimal inhibitory
      concentrations (MIC) were determined for 10 antibiotics using the National
      Committee for Clinical Laboratory Standards (NCCLS) agar dilution methodology.
      Risk factor information including travel history were obtained as part of a case
      control study by conducting telephone interviews with infected individuals. Sixty
      four per cent, 3.4 per cent, 3.4 per cent and 11.2 per cent of C. jejuni isolates
      were resistant to ampicillin (at MIC > 8 mg/L), erythromycin (> 8 mg/L),
      nalidixic acid (> 32 mg/L) and tetracycline (> 8 mg/L), respectively. A diverse
      pattern of antibiotic resistance ('resistotypes') was detected with some change
      occurring over time. Several possible clusters of Campylobacter infections were
      identified based on resistotype. Of seven infections acquired during overseas
      travel, 57 per cent (4/7) were resistant to more than one antibiotic class
      compared to 10 per cent (14/144) of locally-acquired isolates (p=0.004, Fisher
      exact). The potential usefulness of resistotyping as an epidemiological marker is
      worthy of further exploration.

PMID- 12807281
TI  - Low levels of fluoroquinolone resistance in Escherichia coli. A five-year trend
      in Australia measured through the use of TSN Database Australia.
AB  - In many countries, fluoroquinolones are among the most commonly used
      antibacterial drugs. Concerns about bacterial resistance to these and other
      frequently used drugs have been raised by the medical and scientific communities.
      While fluoroquinolone resistance has not yet developed among many bacteria,
      emergence of resistance in Escherichia coli would be a problem as multiple
      resistances to other antibiotics is now a common problem. This paper examines
      trends in resistance to fluoroquinolones in Escherichia coli through analysis of
      data collected from Australian institutions between 1997 and 2001. During the
      study period, norfloxacin and ciprofloxacin were the most frequently tested
      fluoroquinolones in Australian laboratories. An examination of results for
      strains tested simultaneously against both drugs indicated that testing against
      either drug accurately predicted resistance or susceptibility for the other
      (99.7% agreement). Over 400,000 tests were performed to determine the
      fluoroquinolone susceptibility of E. coil. Data were analysed by the test method
      used (Calibrated Dichotomous Sensitivity (CDS) or National Committee for Clinical
      Laboratory Standards (NCCLS)). The data indicate that fluoroquinolone resistance
      in E. coli has not yet emerged as a significant problem in Australia, but there
      are some indications of low level increases in resistance rates. Norfloxacin
      results are likely to be a better guide to fluoroquinolone resistance in this
      species using this method of surveillance.

PMID- 12807282
TI  - Surveillance of hospital-acquired methicillin-resistant Staphylococcus aureus in
      South Australia.
AB  - In September 2001, the South Australian state-wide methicillin-resistant
      Staphylococcus aureus (MRSA) surveillance system was expanded to include three
      surveillance indicators namely: estimated MRSA burden, MRSA morbidity and
      estimated MRSA acquisition. The last two indicator rates have been stratified
      into intensive care unit (ICU) versus non-ICU. Between September 2001 and March
      2002, state-wide MRSA burden rates (prevalence) ranged from 27.5 to 39.8 per
      10,000 occupied bed days (OBDs). Acquisition rates ranged from 28.2 to 69.0 per
      10,000 OBDs (ICU) and 6.3 to 10.1 per 10,000 OBDs (non-ICU). Morbidity rates
      ranged from 12.9 to 43.1 per 10,000 OBDs (ICU) and 3.0 to 5.0 per 10,000 OBDs
      (non-ICU). In association with the changes to surveillance indicators, a new
      monthly surveillance report was developed. Assuring confidentiality to individual
      contributing hospitals has been a major consideration in the development of the
      data collection system. Individual contributors have access only to their own
      indicator rates and pooled state-wide indicator rates. Contributing institutions
      are urged to use great caution if wishing to compare their own rates with state
      wide rates. In particular, contributors are asked to take inter-institutional
      differences in MRSA burden and casemix complexity into account when making such
      comparisons.

PMID- 12807283
TI  - Screening and electronic labelling of ward contacts of vancomycin-resistant
      Enterococcus faecium vanB carriers during a single-strain hospital outbreak and
      after discharge from hospital.
AB  - A large single-strain outbreak of vancomycin-resistant Enterococcus faecium
      (VREF) vanB occurred in Royal Perth Hospital from July to December 2001. When a
      VREF-carrying patient was discovered on a ward, all patients on the ward were
      screened with rectal swabs. A total of 172 patients were colonised, four with
      infections, but no deaths were attributable to VREF. The number of rectal swabs
      required to detect each carrier was recorded. On average four rectal swabs, each
      collected on separate days, were needed to detect more than 90 per cent of the
      172 VREF carriers who were epidemiologically linked to the Royal Perth Hospital
      outbreak. An electronic alert system (Micro-Alert) was used to identify ward
      contacts of VREF carriers and enabled those who had not been screened before
      discharge to be followed-up and screened. Ninety-six contacts were actively
      followed-up in October 2001 and 32 (33.3%) were found to be VREF carriers. From
      28 September 2001 to 30 April 2002, a total of 1,977 ward contacts were screened
      after discharge from hospital and 54 (2.73%) were found to be carrying VREF. We
      conclude that during single-strain outbreaks of vancomycin-resistant enterococci
      in hospitals, patient contacts need to be screened on more than three occasions
      in order to detect most of the carriers and control the outbreak. Secondly,
      electronic labelling and active follow-up of ward contacts of VREF carriers
      resulted in a significant number of carriers being detected who otherwise posed a
      risk of initiating further outbreaks in hospitals if they were readmitted.

PMID- 12807284
TI  - Polymerase chain reaction screening for integrons can be used to complement
      resistance surveillance programs.
AB  - Integrons have been recognised as important contributors to the acquisition and
      dissemination of antibiotic resistance in Gram-negative bacteria. In a collection
      of 19 multi-antibiotic resistant Gram-negative clinical isolates, 47 per cent
      (9/19) of strains were found to contain one or more integron, using a polymerase
      chain reaction (PCR) based screening method. Resistance gene cassettes within the
      integrons were amplified, sequenced and characterised. Antibiotic susceptibility
      testing demonstrated that resistance phenotypes correlated with the resistance
      conferred by gene cassettes identified. PCR-screening for integrons and gene
      cassettes provides a rapid technique for the identification of genetic
      determinants of resistance in Gram-negative bacteria. Such screening could assist
      in guiding treatment regimens and complement existing antibiotic resistance
      surveillance programs by providing information on molecular mechanisms of both
      resistance and resistance dissemination.

PMID- 12807285
TI  - Towards a national surveillance program for antimicrobial resistance in animals
      and animal-derived food.
AB  - One of the major recommendations of the JETACAR report was that a comprehensive
      national surveillance system be established to measure antimicrobial resistance
      to cover medical, food-producing and veterinary areas. While there are a number
      of existing passive surveillance programs on a national, regional and state basis
      in the medical field, there are few analogous programs in the veterinary area,
      and none with a particular emphasis on the food chain. The Commonwealth
      Interdepartmental JETACAR Implementation Group is working with stakeholders to
      develop this aspect of the national surveillance program based on the Guidelines
      published by the world organisation for animal health, the Office International
      des Epizooties.

PMID- 12807286
TI  - Surveillance for antibiotic resistant Escherichia coli in food animals.
AB  - A successful surveillance program for antibiotic resistant Escherichia coli in
      Australia should account for the heterogenous nature of the food-animal
      population. Studies that rely on measurements made on several hundred isolates
      can only satisfy limited objectives because they risk imprecise and biased
      estimation of the presence and distribution of resistance traits. Observations on
      a larger number of isolates are needed to ensure animal, herd and region effects
      are adequately represented so that findings can be extrapolated to the
      appropriate population of interest. An efficient methodology for measuring the
      resistance traits of a large number of isolates is described.

PMID- 12807287
TI  - Antibiotic resistance in animals.
AB  - There is currently no systematic surveillance or monitoring of antibiotic
      resistance in Australian animals. Registration of antibiotics for use in animals
      is tightly controlled and has been very conservative. Fluoroquinolones have not
      been registered for use in food producing animals and other products have been
      removed from the market because of human health concerns. In the late 1970s, the
      Animal Health Committee coordinated a survey of resistance in Salmonella and
      Escherichia coli isolates from cattle, pigs and poultry and in bovine
      Staphylococcus aureus. Some additional information is available from published
      case reports. In samples collected prior to the withdrawal of avoparcin from the
      market, no vancomycin resistant Enterococcus faecium or Enterococcus faecalis
      were detected in samples collected from pigs, whereas some vanA enterococci,
      including E. faecium and E. faecalis, were found in chickens. No vanB enterococci
      were detected in either species. Virginiamycin resistance was common in both pig
      and poultry isolates. Multiple resistance was common in E. coli and salmonellae
      isolates. No fluoroquinolone resistance was found in salmonellae, E. coli or
      Campylobacter. Beta-lactamase production is common in isolates from bovine
      mastitis, but no methicillin resistance has been detected. However, methicillin
      resistance has been reported in canine isolates of Staphylococcus intermedius and
      extended spectrum beta-lactamase producing E. coli has been found in dogs.

PMID- 12807288
TI  - Surveillance for antibiotic resistance in veterinary pathogens from the
      perspective of a regional diagnostic laboratory.
AB  - The Toowoomba Veterinary Laboratory tests for antibiotic resistance through
      passive surveillance of bacterial pathogens from diseased, frequently intensively
      managed, animals. Testing is carried out on the basis of the number of animals
      involved, the nature and severity of the disease and the identity and
      significance of the bacterium, the results guiding the submitting veterinarian in
      implementing appropriate treatment. The antibiotics chosen for testing are those
      that are currently registered for veterinary use and are considered effective in
      the given situation. Testing is carried out according to the current National
      Committee for Clinical Laboratory Standards Approved Standard for Disc
      Susceptibility Tests. This paper presents some results of testing bacterial
      pathogens from cattle and pigs.

PMID- 12807289
TI  - Australian Council on Healthcare Standards infection control clinical indicators.

PMID- 12807290
TI  - Antibiotic resistance and the potential impact of pneumococcal conjugate
      vaccines.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality in young
      children throughout the world, causing both invasive (meningitis, bacteraemia)
      and non-invasive (pneumonia, acute otitis media, sinusitis) infections. Over the
      past few decades, the global emergence of antibiotic-resistant pneumococcal
      strains has complicated disease management. Thus, healthcare practitioners have
      begun to place more emphasis on the judicious use of antibiotics and prevention
      of disease through routine immunisation. Researchers have developed several
      pneumococcal conjugate vaccines, which due to their technology, are effective in
      infants and young children. Currently, one 7-valent pneumococcal conjugate
      vaccine (PNCRM7; Prevenar, Wyeth) is available in various parts of the world and
      has demonstrated excellent efficacy against vaccine-type invasive disease and
      efficacy against pneumonia and otitis media caused by the serotypes included in
      the vaccine. Furthermore, there is evidence suggesting that the use of these
      conjugate vaccines will reduce the need for antibiotics and the subsequent spread
      of antibiotic-resistant pneumococci. Ultimately, when routine pneumococcal
      conjugate vaccination of infants and young children is accompanied by supportive
      education and active disease surveillance as well as judicious use of
      antibiotics, there should be a favourable impact on pneumococcal disease
      incidence in and beyond the vaccinated population.

PMID- 12807291
TI  - Non-antibiotic therapies for infectious diseases.
AB  - The emergence of multiple antibiotic resistant organisms in the general community
      is a potentially serious threat to public health. The emergence of antibiotic
      resistance has not yet prompted a radical revision of antibiotic utilisation.
      Instead it has prompted the development of additional antibiotics. Unfortunately,
      this does not relieve the underlying selection pressure that drives the
      development of resistance. A paradigm shift in the treatment of infectious
      disease is necessary to prevent antibiotics becoming obsolete and, where
      appropriate, alternatives to antibiotics ought to be considered. There are
      already several non-antibiotic approaches to the treatment and prevention of
      infection including probiotics, phages and phytomedicines. There is some evidence
      that probiotics such as Lactobacillus spp. or Saccharomyces boulardii are useful
      in the prevention and treatment of diarrhoea, including Clostridium difficile
      associated diarrhoea that can be difficult to treat and recurs frequently.
      Bacteriophages have received renewed attention for the control of both
      staphylococcal and gastrointestinal infections. Phytomedicines that have been
      utilised in the treatment of infections include artesunate for malaria, tea tree
      oil for skin infections, honey for wound infections, mastic gum for Helicobacter
      pylori gastric ulcers and cranberry juice for urinary tract infections. Many
      infections may prove amenable to safe and effective treatment with non
      antibiotics.

PMID- 12807292
TI  - Distress about sex: a national survey of women in heterosexual relationships.
AB  - As a consequence of the impact of Viagra on male sexual dysfunction, considerable
      attention is now being paid to sexual dysfunctions in women, which might respond
      to pharmacological treatment. Should women's sexual problems be conceptualized in
      the same way as men's? The objective of this study was to assess the prevalence
      of distress about sexuality among women, and examine the predictors of such
      distress, including aspects of the woman's sexual experience, as well as other
      aspects of hercurrent situation. A telephone survey of women used Computer
      Assisted Telephone Interviewing and Telephone-Audio-Computer-Assisted Self
      Interviewing methodology to investigate respondents' sexual experiences in the
      previous month. A national probability sample was used of 987 White or
      Black/African American women aged 20-65 years, with English as first language,
      living for at least 6 months in a heterosexual relationship. The participation
      rate was 53.1%. Weighting was applied to increase the representativeness of the
      sample. A total of 24.4% of women reported marked distress about their sexual
      relationship and/or their own sexuality. The best predictors of sexual distress
      were markers of general emotional well-being and emotional relationship with the
      partner during sexual activity. Physical aspects of sexual response in women,
      including arousal, vaginal lubrication, and orgasm, were poor predictors. In
      general, the predictors of distress about sex did not fit well with the DSM-IV
      criteria for the diagnosis of sexual dysfunction in women. These findings are
      compared with those from other studies involving representative samples of women,
      and the conceptual issues involved in the use of terms such as "sexual problem"
      and "sexual dysfunction" are discussed.

PMID- 12807293
TI  - The prevalence of sexual problems in women: how valid are comparisons across
      studies? Commentary on Bancroft, Loftus, and Long's (2003) 'distress about sex: a
      national survey of women in heterosexual relationships".

PMID- 12807294
TI  - The relation between mood and sexuality in heterosexual men.
AB  - This paper reports on a study of individual variability in the relationship
      between negative mood and sexuality in men. Part 1 involves a questionnaire
      survey of 919 white heterosexual men, asking what typically happens to sexual
      interest and response when (a) depressed and (b) anxious/stressed, using the Mood
      and Sexuality Questionnaire (MSQ). Trait measures of sexual inhibition and
      excitation, depression, anxiety, and sensation seeking were also used.
      Relationships between trait measures and MSQ scores were tested using multiple
      linear and ordinal logistic regression. Of those reporting the experience of
      depression, 9.4% indicated increased and 42% decreased sexual interest when
      depressed; for anxiety/stress, the percentages were 20.6 and 28.3%, respectively.
      Increase in sexual interest during negative mood states was negatively related to
      age and trait measures of sexual inhibition and positively related to depression
      proneness and sexual excitation. In Part 2, the relationship between mood and
      sexuality was explored qualitatively, using in-depth interviews with 43
      participants from Part 1. This supported the findings in Part 1, while finding
      more complex relations with depression than anxiety. Sex when depressed can serve
      needs for intimacy and self-validation as well as sexual pleasure. Sex when
      anxious appears to be more simply related to the calming effect of sexual
      release, plus a possible "excitation transfer" effect of anxious arousal. Further
      research is needed to explore these relationships in clinical mood disorders.
      Paradoxical increases of sexual interest with negative mood may help explain high
      risk as well as "out of control" patterns of sexual behavior.

PMID- 12807296
TI  - Selecting films for sex research: gender differences in erotic film preference.
AB  - The aim of this study was to explore gender differences in sexual responsiveness
      to erotic films that had been selected for their differential appeal for men and
      women. A secondary objective was to identify variables that influence sexual
      arousal and explore whether these variables differ for men and women. Fifteen men
      (M age = 26 yrs) and 17 women (M age = 24 yrs) were presented with 20 film clips
      depicting heterosexual interactions, half of which were female- and the other
      half male-selected, and were asked to rate the clips on a number of dimensions.
      Overall, men found the film clips more sexually arousing than did the women.
      Gender differences in arousal were negligible for female-selected clips but
      substantial for male-selected clips. Furthermore, men and women experienced
      higher levels of sexual arousal to clips selected for individuals of their own
      gender. Cluster regression analyses, explaining 77% of the variance for male and
      65% for female participants, revealed that men's sexual arousal was dependent
      upon the attractiveness of the female actor, feeling interested, and both
      "imagining oneself as a participant" and "watching as an observer." For women,
      with all variables entered, only "imagining oneself as a participant" contributed
      to sexual arousal ratings. The findings suggest that how films are selected in
      sex research is an important variable in predicting levels of sexual arousal
      reported by men and women.

PMID- 12807295
TI  - The relation between mood and sexuality in gay men.
AB  - Negative mood, such as depression and anxiety, is usually associated with a
      decrease in sexual interest and responsiveness. In a minority of individuals, the
      reverse applies, often with an associated tendency to use sex as a mood
      regulator. In homosexual men, the prevalence of depression and anxiety states is
      increased, and the relationship between negative mood and sexuality is,
      therefore, of particular interest. A new brief instrument, The Mood and Sexuality
      Questionnaire, was administered to a sample of 662 gay men, with other trait
      measures of depression and anxiety, propensity for sexual inhibition and sexual
      excitation, sensation seeking, and questions about sexual activity and response.
      Sixteen percent reported that, when depressed, they typically experienced
      increased sexual interest with 7% reporting increased capacity for erectile
      response; 47% and 37% reported a decrease, respectively; the remainder reported
      no change. When experiencing anxiety, 24% reported that they typically
      experienced increased sexual interest, with 14% reporting increased
      responsiveness, and 39% and 31% reporting a decrease. Forty-three men were
      interviewed in depth. The resulting qualitative data showed depression to have a
      more complex relationship to sexual interest than anxiety; other mediating
      mechanisms, such as need for intimacy and self-validation, were sometimes
      involved. Fourteen percent of those interviewed reported reduced concern about
      sexual risk when depressed. Paradoxical increases in sexual interest or activity
      during negative mood states are relevant to high risk sexual behavior among gay
      men, and deserve closer study.

PMID- 12807297
TI  - An experimental study of women's internet personal ads.
AB  - Personal ads are a potentially rich source of information on relationships,
      particularly mating strategies. Most research on personal ads has been limited to
      content analyses of naturally occurring ads. In this study, four "female seeking
      male" ads were placed on two large Internet bulletin boards specializing in such
      ads. The four ads, differing primarily in a few key words representing the
      manipulated independent variable, garnered over 500 e-mail responses in 6 weeks.
      Contrary to prior research and to our prediction, the most popular ad was one in
      which the woman described herself as "financially independent...successful [and]
      ambitious:" producing over 50% more responses than the next most popular ad, one
      in which the woman described herself as "lovely...very attractive and slim." A
      content analysis of responses to the ads revealed that information provided
      varied as a function of the ad they were answering.

PMID- 12807298
TI  - Premature or rapid ejaculation: heterosexual couples' perceptions of men's
      ejaculatory behavior.
AB  - This study investigated the relationship between men's and their female partner's
      perceptions of men's ejaculatory behavior as well as the impact of premature or
      rapid ejaculation on couple functioning. One hundred fifty-two men and their
      female partners provided information about the man's ejaculatory behavior, their
      perceptions of whether the man had a problem with premature or rapid ejaculation
      (RE), their sexual and relationship satisfaction, and their sexual concerns. The
      men's and women's reports on the man's ejaculatory behavior were only moderately
      correlated. In general, the women saw RE as less of a problem for the men than
      their male partners reported for themselves. The women's perceptions of both the
      men's ejaculatory behavior and his affective responses were uniquely related to
      her own and her partner's identification of him as having an RE problem. For both
      the men and the women, having more characteristics of RE was related to lower
      sexual satisfaction, but was unrelated to relationship satisfaction. RE
      characteristics were also related to the number of non-RE sexual concerns
      reported by the men, but not to the number of sexual concerns reported by their
      female partner. However, men and women who identified the man as having an RE
      problem rated RE as having only a slightly negative impact on their own or their
      partners functioning. The results suggest that, for most couples, the timing of
      ejaculation adversely affects sexual satisfaction but not overall relationship
      and personal functioning.

PMID- 12807299
TI  - Effect of deer velvet on sexual function in men and their partners: a double
      blind, placebo-controlled study.
AB  - The use of alternative medicines and herbal remedies is an increasing trend in
      Western societies. For years, people have taken products made of deer velvet for
      their alleged beneficial effects on sexual function. There has been no scientific
      investigation of the effects of deer velvet powder on the sexual functioning of
      human males. This study investigated sexual function in men during a 12-week
      double-blind, placebo-controlled trial of deer velvet. Thirty-two volunteer male
      participants, aged 45-65 years, and their partners, were randomly assigned to
      either the deer velvet or placebo study group. The males took capsules containing
      ground deer velvet or placebo everyday for 12 weeks. Two sexual function
      questionnaires (the International Index of Erectile Function and the Brief Index
      of Sexual Function for Women) used at pre- and posttreatment assessed changes in
      sexual functioning in males and their partners. Blood tests at baseline, and end
      of study, determined levels of sex-related hormones in male participants. There
      were no significant differences in the sexual behavior of the men taking deer
      velvet compared with the men taking placebo capsules. There were no significant
      hormone changes from baseline to the end of the study in either group of men. We
      conclude that in normal males there was no advantage in taking deer velvet to
      enhance sexual function. All alternative health products or nutritional
      supplements should be subjected to randomized placebo-controlled trials to
      determine efficacy.

PMID- 12807300
TI  - The nature of sexual desire: a clinician's perspective.
AB  - Sexual desire is the sum of the forces that lean us toward and away from sexual
      behavior. The ordinary spectrum of sexual desire's intensity ranges between
      aversion, disinclination, indifference, interest, need, and passion. Although
      many individuals have a characteristic pattern of desire throughout their adult
      lives, this spectrum evolves considerably over the life cycle. It is clinically
      useful to think of desire as consisting of drive (biological), motive (individual
      and relationship psychology), and wish (cultural) components. Four master
      variables--age, gender, social situation, and health--affect sexual desire so
      basically that many remain blind to their presence. Five dark paradoxes of desire
      envelop most people at some time in their privacy: (1) Drive and motive are not
      in sync; (2) Behavioral fidelity is often associated with longing for infidelity;
      (3) Despite moral proscriptions, lust is possible; (4) Familiarity diminishes
      sexual interest; and (5) Derogation enhances sexual expression. Clinicians cannot
      afford to simplify desire's inherent contradictions. Researchers must simplify
      desire in order to measure it. In both the clinician's and the researcher's
      hands, sexual desire is a slippery concept.

PMID- 12807301
TI  - Evaluation of the time frame for home ipecac syrup use when not kept in the home.
AB  - INTRODUCTION: The home administration of ipecac syrup remains a recommendation in
      some guidelines for the management of specific pediatric poisonings. A common
      challenge for poison specialists is how to approach the situation when ipecac
      syrup is indicated but not kept in the home. This study examines whether or not
      ipecac syrup can be administered and produce timely emesis in this situation.
      METHODS: Over a 6-month period, a prospective observational study was undertaken
      to determine if ipecac syrup can be administered in a timely manner when it is
      indicated but not available in the home. Cases where ipecac syrup was indicated
      but not kept in the home were included if parents stated that they could obtain
      ipecac within 15 minutes. Timely administration and the onset of emesis were
      defined as < 30 min and < 60 min, respectively. RESULTS: During our study 14,603
      human exposures were evaluated; ipecac syrup was recommended by a poison
      specialist in 75 cases, and 25 of these were included in our study. Ages ranged
      from 1 to 6 years. The mean time to administration of ipecac from exposure time
      was 40 min (SD +/- 14 min). Administration of ipecac syrup occurred in < 30 min
      in 20% of the cases. The mean time to first emesis from exposure was 58 min (SD
      +/- 13). Initial emesis occurred in < 60 min in 36% of the cases. CONCLUSIONS:
      Ipecac syrup was rarely recommended by our center and was frequently unavailable
      when it was recommended. Ipecac syrup often could not be administered in a timely
      manner because it was not kept in the home. Parents of pediatric patients who
      have a significant ingestion should not be referred to purchase ipecac syrup.

PMID- 12807302
TI  - Effect of smoking cessation on mitochondrial respiratory chain function.
AB  - OBJECTIVE: Chronic smoking has been associated with diverse mitochondrial
      respiratory chain (MRC) dysfunction in lymphocytes, although inhibition of
      complex IV activity is the most consistent and relevant finding. These
      mitochondrial abnormalities have been proposed to contribute to pathogenesis of
      diseases associated with tobacco consumption. We assessed MRC function in
      peripheral lymphocytes from heavy smokers after cessation in smoking habit.
      PATIENTS AND METHODS: We studied MRC function from peripheral lymphocytes of 10
      healthy chronic smoker individuals (age 43 +/- 6 years; 50% women) before
      cessation of tobacco consumption (t0), and 7 (t1) and 28 (t2) days after
      cessation. Smoking abstinence was ascertained by measuring carboxyhemoglobin
      levels and carbon monoxide (CO) concentration in exhaled breath. Ten healthy
      nonsmoker individuals matched by age and gender were used as controls.
      Lymphocytes were isolated by Ficoll's gradient, and protein content was
      determined by Bradford's technique. MRC function was studied through double
      means: 1) individual enzyme activities of complex II, III, and IV were analyzed
      by means of spectrophotometry; 2) oxygen consumption was measured
      polarographically using pyruvate, succinate, and glycerol-3-phosphate (complex I,
      II, and III substrates, respectively) after lymphocyte permeabilization. Enzyme
      and oxidative activities were corrected by citrate synthase activity. RESULTS:
      Smokers showed a significant decrease in complex IV activity (p = 0.05) and also
      in respiration of intact lymphocytes (p = 0.05) compared to controls. Eight
      chronic smokers remained abstinent during the study. Smoking cessation was
      associated with a significant recovery of complex IV (p = 0.01) and complex III
      (p = 0.05) activities. Oxidative activities did not show any change during the
      study. CONCLUSION: Chronic smoking is associated with a decrease of complex IV
      and III activities of MRC, which return to normal values after cessation of
      tobacco smoking.

PMID- 12807303
TI  - Unintentional human exposure to tilmicosin (Micotil 300).
AB  - BACKGROUND: Tilmicosin phosphate is a macrolide antibiotic that is used to treat
      cattle for pathogens that cause Bovine Respiratory Disease. CASE REPORT: A 28
      year-old man with no prior history of heart disease developed severe chest pain,
      inverted T waves, and intraventricular conduction delay on EKG and mild elevation
      of cardiac enzymes 5 hours after unintentional injection of less than half of a
      12cc syringe filled with Micotil 300 (tilmicosin phosphate 300 mg/mL, propylene
      glycol 25%, phosphoric acid, water for injection). The patient made an uneventful
      recovery after hospitalization. CONCLUSIONS: This case provides evidence that
      unintentional injection of tilmicosin can cause cardiac symptoms and laboratory
      evidence of myocardial injury. Tilmicosin should always be administered by
      properly trained personnel who are using techniques designed to reduce the risk
      of accidental self-injection.

PMID- 12807304
TI  - Herbal infusions used for induced abortion.
AB  - Plants and herbs have been used to induce abortions but there is very little
      published information describing the commonly used ones. The purpose of this
      report is to describe the herbal products used to induce abortions, and to
      enhance awareness and understanding of their toxic effects. A descriptive
      retrospective survey was conducted on the calls received by the Montevideo Poison
      Centre between 1986 and 1999 concerning the ingestion of herbal infusions with
      abortive intent. A total of 86 cases involving 30 different plant species were
      identified. The species most frequently involved were ruda (Ruta
      chalepensis/graveolens), cola de quirquincho (Lycopodium saururus), parsley
      (Petroselinum hortense), and an over-the-counter herbal product named
      Carachipita. The components of Carachipita are pennyroyal (Mentha pulegium),
      yerba de la perdiz (Margiricarpus pinnatus), oregano (Origanum vulgare), and
      guaycuri (Statice brasiliensis). Abortion occurred in 23 cases after the
      ingestion of parsley, ruda, Carachipita, celery, Cedron, francisco alvarez,
      floripon, espina colorada. Out of the 23 cases, 15 involved the only the
      ingestion of plants, 4 cases used injected drugs (presumably hormones), and in 4
      cases there was associated self-inflicted instrumental manipulation. Multiple
      organ system failure occurred in those patients who had ingested ruda (alone or
      in combination with parsley or fennel), Carachipita, arnica, or bardana. Deaths
      occurred in one case of Carachipita ingestion and in 4 cases of ruda ingestion (2
      cases of ruda alone, 2 cases of ruda with parsley and fennel). Self-inflicted
      instrumental manipulations were found in 4 of the patients with multiple organ
      system failure and in one of those who died. The results of this report are not
      conclusive, but it appears that the ingestion of plants to induce abortion
      involves the risk of severe morbidity and mortality.

PMID- 12807305
TI  - Envenomation by the Mexican beaded lizard: a case report.
AB  - BACKGROUND: Envenomations by venomous lizards are rare. A single report of
      envenomation by a Mexican beaded lizard (Heloderma horridum) has been published.
      Further, anaphylaxis secondary to lizard envenomation has only been reported with
      the Gila monster. We report an envenomation that resulted in both systemic
      toxicity and anaphylaxis. CASE REPORT: A 40-year-old male was bitten on his hand
      by a captive Mexican beaded lizard. The patient experienced severe local pain,
      dizziness, vomiting, and diaphoresis. Upon arrival to the hospital, he was
      lethargic, vomiting, and in severe pain with marked swelling of his hand, lips,
      and tongue. His blood pressure was 110/63 mm/Hg with a pulse of 60 beats/minute.
      The patient's oxygen saturation decreased to 55%, and he required oxygen,
      although cyanosis was not observed. He was treated with normal saline,
      diphenhydramine, methylprednisolone, famotidine, ondansetron, morphine, and
      hydromorphone. The patient was admitted to intensive care where he continued to
      complain of severe pain requiring morphine. Local X-ray revealed only soft tissue
      swelling. Remarkable initial laboratory values included WBC 18,500 k/mm3 with 80%
      segs. Over the next eight hours, the patient's symptoms gradually improved. He
      had persistent local swelling at the bite site along with erythematous streaking
      up the forearm. He had an uneventful hospital course until his eventual discharge
      the following day. CONCLUSION: Significant envenomations by members of the
      Helodermatidae family are rare. Systemic toxicity usually resolves within one to
      two days with supportive care. Prior envenomations may predispose patients to
      anaphylactic reactions.

PMID- 12807306
TI  - A case of accidental ingestion of ant bait containing fipronil.
AB  - A 77-year-old woman accidentally ingested a commercial ant bait containing
      fipronil without development of obvious toxicity, supporting the safety of this
      new insecticide as demonstrated in animal studies. However, concentrated
      agricultural products may be more toxic, and the potential for seizures should
      not be overlooked. The pharmacological action, mechanism of selective insect
      toxicity, and clinical effects of fipronil are discussed.

PMID- 12807307
TI  - Methylergometrine poisoning in children: review of 34 cases.
AB  - Methylergometrine is often used in the management of the third stage of labor and
      for treatment of prevention of puerperal hemorrhage. Intoxication in newborns is
      rare but may lead to severe complications. We reviewed 34 cases of
      methylergometrine poisoning that occurred in Belgium between 1969 and 1999.
      Fourteen patients were newborns and 20 were older children. Twenty-nine patients
      were exposed by the oral route, 3 by the intranasal route, and 2 by the
      intramuscular route. Oral exposure was associated mostly with gastrointestinal
      symptoms, but one newborn required mechanical ventilation for apnea.
      Intramuscular exposure was associated with severe complications, including apnea,
      coma, and convulsions. We describe the first case of oral methylergometrine
      poisoning requiring mechanical ventilation and alert physicians that oral
      exposure to methylergometrine may lead to severe complications.

PMID- 12807308
TI  - Endogenous formate elimination and total body clearance during hemodialysis.

PMID- 12807309
TI  - Antivenoms: editorial commentary.

PMID- 12807310
TI  - Clinical toxinology--where are we now?
AB  - Clinical toxinology encompasses a broad range of medical conditions resulting
      from envenomation by venomous terrestrial and marine organisms, and also
      poisoning from ingestion of animal and plant toxins. Toxin-related disease is an
      important cause of morbidity and mortality worldwide, particularly in the
      tropical and subtropical continents. Snake bite is the single most important
      toxin-related disease, causing substantial mortality in many parts of Africa,
      Asia, and the Americas. The most important snake families are Viperidae and
      Elapidae, causing a range of clinical effects including local necrosis,
      neurotoxicity, coagulopathy and hemorrhage, myotoxicity and renal toxicity. These
      effects vary according to geography and group of snake. Arachnid envenomation
      results mainly in morbidity, particularly scorpion stings which can cause severe
      systemic envenomation. Spider bite is far less of a problem, and the majority of
      medically important cases can be attributed to widow spiders (Latrodectus spp.)
      and recluse spiders (Loxosceles spp.). Marine-related envenomations are common,
      but severe effects are less so. Plant and mushroom poisoning occur in most parts
      of the world, but the types and methods of poisoning vary considerably between
      continents. Management of toxin-related disease is often difficult, and in many
      cases meticulous supportive care is all that is available. The mainstay of
      treatment is the use of antivenoms for many envenomations and poisoning, although
      these do not exist for all dangerous organisms. Unfortunately antivenoms are not
      an economically viable product, so development and manufacture of these agents
      have been limited. This is now further worsened by a current shortage of
      antivenom. There is a need for improvement in the preventionand management of
      toxin-related disease. This will require well-designed studies to define the
      extent of the problem, initiatives to improve the prevention and management of
      these conditions, and development of new, and continuation of current, antivenom
      supplies.

PMID- 12807311
TI  - Snake antivenoms.

PMID- 12807312
TI  - Antivenom treatment in arachnidism.
AB  - Envenomation by arachnids causes significant medical illness worldwide. Scorpion
      sting is the most important arachnid envenomation causing adult morbidity and
      pediatric mortality. Important groups of spiders include the widow spiders
      (Latrodectus spp.), the recluse spiders (Loxosceles spp.), and two spiders
      confined to single countries: the Australian funnel web spider (Atrax and
      Hadronyche spp.) and the armed spider (Phoneutria spp.) from Brazil. There are
      four widow spider antivenoms available, including the Australian redback spider
      antivenom and the American black widow antivenom. Despite good in vitro animal
      work demonstrating effective neutralization with these antivenoms, and cross
      reactivity between many species, there continues to be a reluctance to use them
      in some countries. They are both associated with a relatively low rate of
      allergic reactions. Redback antivenom is routinely used by the intramuscular
      route, which may not be as effective as intravenous use based on clinical
      experience and animal studies. Antivenoms are available for Loxosceles spp., but
      there is little evidence to support their effectiveness, particularly against
      local effects. The Australian funnel web spider causes severe neurotoxic
      envenomation, and antivenom appears to be effective in reported cases. An
      antivenom exists for the Brazilian armed spider, but is used in only a minority
      of cases. Many scorpion antivenoms exist worldwide, but there remains significant
      controversy regarding their efficacy. Animal and human venom level studies
      demonstrate neutralization of circulating venom in systemic envenomation.
      Clinical experience in countries where antivenom has been introduced suggests it
      has reduced pediatric mortality. However, three controlled trials demonstrated
      that antivenom was not effective, but these included few severe cases. Until
      controlled trials of antivenom in systemically envenomated patients are
      undertaken, antivenom use appears justified in severe envenomation. Although
      envenomation from arthropods is common, no antivenoms exist for these, excepting
      Lonomia caterpillars in South America, and Ixodes paralysis ticks in Australia.

PMID- 12807313
TI  - Marine antivenoms.
AB  - There is an enormous diversity and complexity of venoms and poisons in marine
      animals. Fatalities have occurred from envenoming by sea snakes, jellyfish,
      venomous fish such as stonefish, cone snails, and blue-ringed octopus. Deaths
      have also followed ingestion of toxins in shellfish, puffer fish (Fugu), and
      ciguatoxin-containing fish. However antivenoms are generally only available for
      envenoming by certain sea snakes, the major Australian box jellyfish (Chironex
      fleckeri) and stonefish. There have been difficulties in characterizing the
      toxins of C. fleckeri venom, and there are conflicting animals studies on the
      efficacy of C. fleckeri antivenom. The vast majority of C. fleckeri stings are
      not life-threatening, with painful skin welts the major finding. However
      fatalities that do occur usually do so within 5 to 20 minutes of the sting. This
      unprecedented rapid onset of cardiotoxicity in clinical envenoming suggests that
      antivenom may need to be given very early (within minutes) and possibly in large
      doses if a life is to be saved. Forty years of anecdotal experience supports the
      beneficial effect of stonefish antivenom in relieving the excruciating pain after
      stonefish spine penetration. It remains uncertain whether stonefish antivenom is
      efficacious in stings from spines of other venomous fish, and the recommendation
      of giving the antivenom intramuscularly needs reassessment.

PMID- 12807314
TI  - Acute plant poisoning and antitoxin antibodies.
AB  - Plant poisoning is normally a problem of young children who unintentionally
      ingest small quantities of toxic plants with little resulting morbidity and few
      deaths. In some regions of the world, however, plant poisonings are important
      clinical problems causing much morbidity and mortality. While deaths do occur
      after unintentional poisoning with plants such as Atractylis gummifera (bird-lime
      or blue thistle) and Blighia sapida (ackee tree), the majority of deaths globally
      occur following intentional self-poisoning with plants such as Thevetia peruviana
      (yellow oleander) and Cerbera manghas (pink-eyed cerbera or sea mango).
      Antitoxins developed against colchicine and cardiac glycosides would be useful
      for plant poisonings--anti-digoxin Fab fragments have been shown to be highly
      effective in T. peruviana poisoning. Unfortunately, their great cost limits their
      use in the developing world where they would make a major difference in patient
      management. Therapy for some other plant poisonings might also benefit from the
      development of antitoxins. However, until issues of cost and supply are worked
      out, plant antitoxins are going to remain a dream in many of the areas where they
      are now urgently required.

PMID- 12807315
TI  - Pelvic osteotomy for acetabular dysplasia.

PMID- 12807316
TI  - Lessons learned after more than 250 periacetabular osteotomies.
AB  - The Bernese periacetabular osteotomy (PAO) has become the procedure of choice in
      many centers for the treatment of young patients with symptomatic hip dysplasia
      in the absence of severe secondary arthrosis. This article concerns our
      institution's "learning curve" with this procedure and focuses on patient
      selection, exposure, technical aspects of performing the bone cuts, mobilizing
      the fragment, and obtaining proper correction.

PMID- 12807317
TI  - Polygonal triple (Kotz) osteotomy in the treatment of acetabular dysplasia: 17
      patients (19 hips) with 4-9 years of follow-up.
AB  - We reviewed 19 hips in 17 patients between 17 and 33 years of age, who underwent
      a Kotz polygonal triple osteotomy. Their average follow-up was 7 (4.5-9) years.
      Although 13 patients had less pain after surgery, 3 continued to limp. The
      average corrections were 36 degrees for the center-edge angle, 31 degrees for the
      vertical center-edge angle and 19 degrees for Sharp's angle. 3 patients developed
      transient palsy of the sciatic nerve, and 3 asymptomatic nonunion of the ischium
      or pubic bone. The degree of arthrosis decreased in 10 hips.

PMID- 12807318
TI  - Two-incision technique for rotational acetabular osteotomy: good outcome in 35
      hips.
AB  - We have developed a 2-incision technique for rotational acetabular osteotomy.
      This includes both an extraperitoneal and an anterolateral exposure of the pelvic
      bones allowing an unconstrained approach without dissection of the muscle
      insertion. 2 plates are used to stabilize the osteotomy and full range motion of
      the hip is permitted within 2 days of surgery, while weight bearing is restricted
      for 6 weeks after the operation. We reviewed the complications and technical
      results in 27 patients (28 hips) after a minimum follow-up of mean 3 (1-5) years.
      No major surgical complications occurred, but dysfunction of the lateral femoral
      cutaneous nerve occurred frequently (14 patients). The radiographical correction
      of the femoral head covering was similar to those in previous reports of
      rotational osteotomy. The range of hip motion was not affected by the operation.
      A significant increase in the mean Merle D'Aubigne and Harris Hip scores was
      observed in a subgroup of 20 patients with a minimum follow-up of 2 years. In
      conclusion, the method we have used is safe and the early results are
      satisfactory.

PMID- 12807319
TI  - Excellent results of HA coating on a grit-blasted stem: 245 patients followed for
      8-12 years.
AB  - We report the outcome of a grit-blasted titanium stem designed for press-fit
      insertion and entirely plasma sprayed with HA. During the years 1988-1993, we
      performed 323 primary total hip replacements in 276 patients (189 women) with a
      HA-coated prosthesis. Their mean age was 48 (15-79) years. During the follow-up,
      12 patients died. 19 other patients did not attend the follow-up examination, but
      had no major symptoms according to telephone interviews and written replies.
      Thus, 245 patients (291 hips) were followed for a mean of 10 (8-12) years with
      radiographic and clinical examinations. Only 1 stem was revised due to mechanical
      failure. None were revised because of infection. Osteolysis was significantly
      associated with wear, and wear was significantly associated with the size of the
      femoral head. We found a small amount of proximal bone loss (37/291) and a low
      incidence of distal hypertrophy of the bone (23/291). These observations indicate
      an essentially physiological weight distribution from the stem to the femoral
      bone. The changes in the bone confirmed that the femoral component was well fixed
      in asymptomatic patients. To conclude, we found excellent 8-12-year results with
      a fully HA-coated femoral prosthesis designed for press-fit insertion.

PMID- 12807320
TI  - Strut allografts for failed treatment of periprosthetic femoral fractures: good
      outcome in 13 patients.
AB  - Strut allografts are not recommended after a femoral shaft exposure, because they
      may endanger the femoral blood supply. Up till now, we have seen no clinical
      reports on this problem. We treated 13 consecutive patients with very large
      anteromedial and anterolateral femoral strut allografts to restabilize
      periprosthetic fractures which had become loose after a previous attempt at
      surgical fixation (Vancouver type B fractures with severe bone loss). In 8 cases,
      the stem was revised in conjunction with the use of strut allografts and in 5
      cases, strut allografts alone were used. All refractures and nonunions healed
      without further treatment. At a mean follow-up of 3 (1.2-7) years, the mean
      Harris Hip Score was 78 (65-92). All strut grafts showed ingrowth with
      augmentation of periprosthetic bone on the radiographs. There were 3
      complications, 1 nonprogressive subsidence of a revision stem (fibrous stable), 1
      deep hematoma and 1 partial lesion of the sciatic nerve. In this series, strut
      grafts gave reliable healing with augmentation of the host bone stock despite
      previous femoral exposure, severe bone loss, adverse type of fracture, and
      persistent instability at the index operation.

PMID- 12807321
TI  - An in-vitro investigation of the CPS-Plus femoral stem: influence of the proximal
      centraliser on cement pressurisation during stem insertion.
AB  - The CPS-Plus stem is designed for use with a proximal and distal stem
      centraliser. This in-vitro study examined the cement pressurisation achieved
      during insertion of the CPS-Plus femoral stem into a model femur. Cement
      pressures were measured at proximal, mid and distal stem levels. Pressures were
      recorded during insertion of the CPS-Plus stem with both proximal and distal
      centralisers and compared with those achieved when only a distal centraliser was
      used with digital occlusion of the proximal femur. The CPS-Plus with a proximal
      centraliser generated significantly greater cement pressures than the CPS-Plus
      without a proximal centraliser at proximal and mid-stem regions. The use of a
      proximal stem centraliser may improve the cement-bone interdigitation and shear
      strength at the cement-bone interface, particularly in the region of the proximal
      femur.

PMID- 12807322
TI  - Scintigraphic image patterns in dysplastic coxarthrosis: evaluation with
      reference to radiographic findings in 210 hips.
AB  - Little is known about scintigraphic image patterns in the various stages of
      coxarthrosis. We assessed bone scintigraphy in 159 patients (210 hips) with
      dysplastic arthrosis of the hip. Scintigraphic images were divided into 5 types
      related to the radiographic stages of the disease. The scintigraphic images
      showed little, if any, uptake in the stage of prearthrosis. In the early stage,
      we found an increase in uptake in the weight bearing area in 30% of cases. In the
      advanced stage, more than half of the cases had an increase in uptake in the
      medial side of the joint and in the weight bearing area. In the terminal stage, a
      marked increase in uptake in the weight bearing area was commonest. Since the
      osteoblastic reaction intensified, a marked increase in uptake was seen not only
      in the weight bearing area, but also throughout the entire joint. These types of
      scintigraphic patterns, which change with the stage of coxarthrosis, seem to
      reflect the natural course of the disease. All hips with rapid progression of the
      disease showed a marked increase in uptake of radionuclide the entire joint at
      earlier stages.

PMID- 12807323
TI  - External fixators for pelvic fractures: comparison of the stiffness of current
      systems.
AB  - We evaluated the stiffness of external fixation (EF) systems with a reproducible,
      standardized human pelvic replica of aluminum and perspex in which a type C
      pelvic ring injury was created. 12 EF systems were analyzed in 2 situations that
      necessarily occur during a walking cycle. Endpoints were defined as 15 mm of
      dislocation or tolerance of the maximum load in each situation. In the no
      weightbearing situation, all except 2 fixators failed; in the weightbearing
      situation, all fixators failed. Single bar systems performed better than frame
      configurations. Stability provided by any external fixator is low, and in the
      case of a type C pelvic ring injury, it is insufficient for patient mobilization
      and weightbearing. Single bar systems provide more stability than frames.

PMID- 12807324
TI  - Surveillance of surgical-site infections in orthopedics.

PMID- 12807325
TI  - Quality of the surveillance of surgical wound infections: a 10-year prospective
      study of 12,364 wounds.
AB  - We did a survey of postoperative wound infection rates in our department over a
      10-year period. It was based on the results of forms completed by surgeons in the
      department after each operation and when an infection was diagnosed (primary
      registration). These forms were sent to the electronic data processing department
      for registration of data in a database. Every third month, detailed reports of
      the data were discussed with the surgeons. The quality of this routine survey was
      evaluated as follows: 1) Every year, the year's data in the surveys database were
      compared with those in the National Patient Register and, in case of
      discrepancies, the patient's records were checked and missing information about
      the operation and infections were recorded in the surveys database (secondary
      registration). 2) In case of a primary registered infection, the patient's record
      was carefully examined. Infections not fulfilling the criteria for an infection
      were called registration failures. The primary registration of operations reached
      an acceptable level (about 95%) after 5 years of the survey, but the recording of
      infections was unreliable throughout the study due to an unacceptably low
      registration rate (about 60%) and to a high rate of registration failures.

PMID- 12807326
TI  - Satisfactory long-term results after Eden-Hybbinette-Alvik operation for
      recurrent anterior dislocation of the shoulder: 6-20 years' follow-up of 52
      patients.
AB  - We studied the outcome after the Eden-Hybbinette-Alvik operation for recurrent
      anterior shoulder dislocation in 52 patients after a mean of 14 (6-20) years.
      Their mean age at operation was 26 years. Redislocation occurred in 2/52
      patients. The success rate was 49/52, when rated by the patients, and 38/45,
      using the Carter-Rowe shoulder score. 44/52 reported no pain, 48/52 no
      limitations at work and 37/51 no limitations in sports. Mild and moderate
      arthrosis were found in 24/45 on the operated side and 9/45 on the uninvolved
      side. None (0/21) of the patients without arthrosis and 5/24 of those with
      arthrosis in the operated shoulder reported mild or moderate pain.

PMID- 12807327
TI  - Radiographic classification of glenohumeral arthrosis.
AB  - We studied the interobserver agreement of two radiographic classification systems
      for evaluation of glenohumeral arthrosis in 40 patients at long-term follow-up
      after the Eden Hybbinette operation for habitual dislocation of the anterior
      shoulder. Both observers agreed that none of the patients had severe arthrosis.
      The Samilson-Prieto system showed agreement using the classification in 35 of 40
      operated shoulders (kappa 0.76). The Kellgren-Lawrence system showed agreement
      using the classification in 23 of 40 operated shoulders (kappa 0.36). The rate of
      arthrosis in the operated shoulder ranged from 0.2 to 0.6, depending on the
      classification system and the observer. None of the patients without arthrosis,
      but one fifth of those with arthrosis reported pain. The Samilson-Prieto
      classification is preferable because it is simple to use and has excellent
      interobserver agreement.

PMID- 12807328
TI  - Activated PMNs lead to oxidative stress on chondrocytes: a study of swine knees.
AB  - Using an in vitro model, based on primary cultured chondrocytes, we examined
      possible oxidative injury caused by activated polymorphonuclear neutrophil
      granulocytes (PMNs), which are thought to be part of the pathomechanism of
      hemarthrosis. Chondrocytes were isolated from swine knee joints and divided into
      three groups. Pure chondrocytes acted as the control population (group I). PMNs
      from the systemic circulation, and hydrogen peroxide (as an artificial source of
      reactive oxygen species (ROS)) were added to groups II and III, respectively. All
      cultures were incubated for 6 hours. After the experiment, lipid membrane
      degradation by ROS was assessed by monitoring changes in the levels of
      malondialdehyde (MDA) and 4-hydroxyalkenal contents of the chondrocyte specimens.
      Changes in the endogenous scavenger status of the chondrocytes were characterized
      by measuring of reductions in glutathione (GSH) concentration and superoxide
      dismutase (SOD) activity. Significant increases in MDA/4-hydroxyalkenal levels
      and SOD activity as well as an expressive reduction in intracellular GSH content
      were highlighted by comparing the control to the PMN- or H2O2-treated cell
      populations. These findings confirm previous suggestions that PMN-derived ROS
      contribute to degradation of cartilage in hemarthrosis.

PMID- 12807329
TI  - The effect of medial collateral ligament insufficiency on the reconstructed
      anterior cruciate ligament: a study in the rabbit.
AB  - The treatment for severe combined anterior cruciate ligament (ACL) and medial
      collateral ligament (MCL) ruptures is disputed. Using a rabbit model, we examined
      the effect of insufficiency of medial structures on the reconstructed ACL in
      combined ACL and MCL injury. 40 rabbits were divided into 2 groups. In both
      groups, ACL was subjected to in situ freeze-thaw treatment. In group F, only
      freeze-thaw treatment of ACL was given. In group FM, partial resection of MCL was
      also done. We killed 5 rabbits on each of 4 occasions: immediately after the
      operation (time 0), at 6, 12 and 24 weeks postoperatively. At each time, we
      measured valgus instability and mechanical properties of the ACL. Valgus
      instability in group FM persisted from time 0 to 24 weeks, and was significantly
      greater than that in group F. The tensile strength and tangent modulus of the ACL
      in group FM were lower than those in group F. We found that continuous valgus
      instability reduces the mechanical properties of the in situ frozen ACL.

PMID- 12807330
TI  - External rotation stress imaging in syndesmotic injuries of the ankle: comparison
      of lateral radiography and radiostereometry in a cadaveric model.
AB  - We compared the value of 7.5 Nm external rotation stress in diagnosing
      tibiofibular syndesmotic injuries of the ankle on lateral radiographs with
      radiostereometric analysis (RSA) in 10 cadaveric legs. After sectioning 2
      ligaments, RSA showed an increase in posterior translation and external rotation
      of the fibula. This increase in posterior translation was smaller than the
      posterior displacement of the fibula on the lateral radiograph, and RSA showed
      mainly an increase in external rotation of the fibula that can not be measured on
      conventional radiographs. We conclude that instability of the syndesmosis in
      cadaveric ankles can be detected with 7.5 Nm external rotation stress RSA, but
      that external rotation stress lateral radiography is unreliable.

PMID- 12807331
TI  - Simple end-to-end suture versus augmented repair in acute Achilles tendon
      ruptures: a retrospective comparison in 98 patients.
AB  - We retrospectively compared the results in 98 patients with an acute Achilles
      tendon rupture treated with an augmented tendon repair (n = 59) to patients with
      an end-to-end suture (n = 39) after an average follow-up of 44 (22-69) months. 7
      patients were operated on more than 2 weeks after the rupture, all with
      augmention. The complication rates in the augmention group were 0.1 and in the
      end-to-end suture group 0.2. We found no differences in subjective outcome or
      rerupture rate between the groups. In the augmentation group, the rate of
      complications was higher in those operated on after 2 weeks than in those
      operated on before. A simple end-to-end suture seems sufficient.

PMID- 12807332
TI  - Hallux valgus: immediate operation versus 1 year of waiting with or without
      orthoses: a randomized controlled trial of 209 patients.
AB  - Hallux valgus operations can not always be done immediately because of long
      waiting lists. In this study, 209 consecutive patients (mean age 48 years, 93%
      female) with a painful hallux valgus were randomized into 3 groups: immediate
      operation or 1 year waiting with or without foot orthoses. The follow-up period
      was 2 years. The main outcome measurement was the intensity of pain during
      walking. During the first year, 64/71, 0/69 and 4/69 patients were operated on in
      the surgery, orthosis and no orthosis groups, respectively, and during the 2-year
      follow-up, 66, 43 and 48, respectively. At the 1-year follow-up, the pain was
      least intense in the surgery group. At the 2-year follow-up, the intensity of
      pain was similar in all groups. The satisfaction with treatment was best in the
      surgery and orthosis groups. The total costs of care were similar in all groups.
      We conclude that immediate operation is superior to delayed operation or foot
      orthoses. However, if this is not possible because of limited possibilities for
      surgery, waiting for 1 year, with or without an orthosis, does not jeopardize the
      final outcome.

PMID- 12807333
TI  - Infection following total hip arthroplasty with a hydroxyapatite-coated
      prosthesis: histology and histomorphometry 6 years after implantation and
      infection--a case report.

PMID- 12807334
TI  - The sequelae of late diagnosis in tuberculous flexor tenosynovitis of the hand--a
      report of 2 cases.

PMID- 12807335
TI  - Wedge excision chondroplasty of the knee in dysplasia epiphysealis hemimelica-
      report of 2 cases.

PMID- 12807336
TI  - Cox inhibitors and bone healing.

PMID- 12807337
TI  - Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults
      with acute bronchitis. A randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: New evidence-based treatment options are required to avoid antibiotic
      overuse in acute bronchitis and to replace potentially inefficacious initial
      antibiotic treatment. OBJECTIVE: To evaluate the efficacy and safety of an
      extract of Pelargonium sidoides (EPs 7630) compared to placebo in patients with
      acute bronchitis. DESIGN: Randomized, double-blind, placebo-controlled trial
      using a multi-stage adaptive design. SETTING: 36 primary care physicians
      (investigators) at the out-patient care setting. PATIENTS: 468 adults with acute
      bronchitis present < or = 48 hours, Bronchitis Severity Score (BSS) > or = 5
      points, and informed consent. INTERVENTION: EPs 7630 or placebo (30 drops three
      times daily) for 7 days. MEASUREMENT: The primary outcome criterion was the
      change of BSS on day 7. RESULTS: The decrease of BSS from baseline to day 7 was
      5.9 +/- 2.9 points under EPs 7630 (n = 233), and 3.2 +/- 4.1 points under placebo
      (n = 235). The 95% CI for the difference of effects between the two treatment
      groups (EPs 7630 minus placebo) was calculated as [-3.359; -2.060] showing a
      significant superiority of EPs 7630 compared to placebo on day 7 (p < 0.0001).
      Working inability decreased to 16% in the EPs 7630 group compared to 43% in the
      placebo group (p < 0.0001). In addition, the duration of illness was
      significantly shorter for patients treated with EPs 7630 compared to placebo (p <
      0.001). Within the first four days, onset of treatment effect was recognized in
      53.6% of patients under EPs 7630 compared to 36.2% of patients under placebo,
      only (p < 0.0001). Adverse events (AEs) occurred in 36/468 patients (EPs 7630:
      20/233 patients, placebo: 16/235 patients). All events were assessed as non
      serious. CONCLUSION: EPs 7630 was superior in efficacy compared to placebo in the
      treatment of adults with acute bronchitis. Treatment with EPs 7630 clearly
      reduced the severity of symptoms and shortened the duration of working inability
      for nearly 2 days.

PMID- 12807338
TI  - Pharmacological profile of extracts of Pelargonium sidoides and their
      constituents.
AB  - In areas of southern Africa, aqueous extracts from the roots of Pelargonium
      sidoides are employed to cure various disorders. Nowadays, a modern formulation
      (EPs 7630), elaborated from the traditional herbal medicine, is successfully used
      for the treatment of respiratory tract diseases. We previously observed that root
      extracts of P. sidoides and their representative constituents exhibit moderate
      antibacterial and significant immunomodulatory capabilities. The present study
      was performed to further assess the efficacy and mode of action for these
      pharmacological activities. The results indicate that P. sidoides extracts may
      well possess antimycobacterial activity as claimed in traditional uses.
      Furthermore, significant antibacterial properties against multi-resistant
      Staphylococcus aureus strains as well as TNF-inducing potencies and prominent
      interferon-like activities in supernatants of sample-activated bone marrow
      derived macrophages were observed using several functional assays. In addition,
      EPs 7630 stimulated the synthesis of IFN-beta in MG 63 cells as demonstrated by a
      specific enzyme immunoassay. For gallic acid, a characteristic constituent,
      evidence for the expression of iNOS and TNF-alpha transcripts in stimulated RAW
      264.7 cells and, hence, activation at the transcriptional level was revealed by
      RT-PCR. The present results, when taken together with the recently reported
      pharmacological activities, provide for a rationale basis of the utilization of
      EPs 7630 in the treatment of respiratory tract infections.

PMID- 12807339
TI  - Treating depression comorbid with anxiety--results of an open, practice-oriented
      study with St John's wort WS 5572 and valerian extract in high doses.
AB  - Depressive disorders in comorbidity with anxiety disorders represent an
      frequently diagnostic and therapeutic problem. The studies quoted here prove that
      the symptoms associated with anxiety that severely afflict patients can be
      clearly improved more quickly with a combination therapy of St John's wort
      extract and valerian extract than with St John's wort monotherapy. The
      combination therapy was well tolerated, no significant side-effects occurred.
      Further studies are necessary to compare the combination treatment with other
      forms of therapy (serotonin- and noradrenalin re-uptake inhibitors).

PMID- 12807340
TI  - Topical treatment of atopic dermatitis with St. John's wort cream--a randomized,
      placebo controlled, double blind half-side comparison.
AB  - BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial
      effect of hyperforin, which is a major constituent of Hypericum perforatum L.
      (Saint John's wort). OBJECTIVE: In the present half-side comparison study we
      assessed the efficacy of a cream containing Hypericum: extract standardised to
      1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for
      the treatment of subacute Atopic Dermatitis. The study design was a prospective
      randomised placebo-controlled double-blind monocentric study. METHODS: In twenty
      one patients suffering from mild to moderate Atopic Dermatitis (mean SCORAD 44.5)
      the treatment with verum or placebo was randomly allocated to the left or right
      site of the body, respectively. The patients were treated twice daily over a
      period of four weeks. Eighteen patients completed the study. The severity of the
      skin lesions on the left and right site was determined by means of a modified
      SCORAD-index (primary endpoint). RESULTS: The intensity of the eczematous lesions
      improved on both sites of treatment. However, the hypericum-cream was
      significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p
      < 0.05). Skin colonisation with Staphylococcus aureus was reduced by both verum
      and placebo, showing a trend to better antibacterial activity of the hypericum
      cream (p = 0.064). Skin tolerance and cosmetic acceptability was good or
      excellent with both the hypericum-cream and the vehicle (secondary endpoints).
      CONCLUSION: Taken together, the present study shows a significant superiority of
      the hypericum-cream compared to the vehicle in the topical treatment of mild to
      moderate Atopic Dermatitis. The therapeutic efficacy of the hypericum-cream,
      however, has to be evaluated in further studies with larger patient cohorts, in
      comparison to therapeutic standards (i.e. glucocorticoids).

PMID- 12807341
TI  - Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in
      Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre
      clinical trial in 129 out-patients.
AB  - OBJECTIVE: An 8-week randomized, reference-controlled, double-blind, multi-centre
      clinical trial investigated Kava-Kava LI 150 in Generalized Anxiety Disorder
      (GAD; ICD-10: F41.1). METHOD: 129 out-patients received either 400 mg Kava LI
      150, 10 mg Buspirone or 100 mg Opipramol daily for 8 weeks. At week 9, subjects
      were seen to check for symptoms of withdrawal or relapse. Primary outcome
      measures comprised the HAMA scale and the proportion of responders at week 8.
      Secondary measures were the Boerner Anxiety Scale (BOEAS), SAS, CGI, a self
      rating scale for well-being (Bf-S), a sleep questionnaire (SF-B), a quality-of
      life questionnaire (AL) and global judgements by investigator and patients.
      RESULTS: In 127 patients (ITT) no significant differences could be observed
      regarding all efficacy and safety measures. About 75% of patients were classified
      as responders (50% reduction of HAMA score) in each treatment group, about 60%
      achieved full remission. CONCLUSION: Kava-Kava LI150 is well tolerated and as
      effective as Buspirone and Opipramol in the acute treatment of out-patients
      suffering from GAD.

PMID- 12807342
TI  - A newly developed extract (Ze 339) from butterbur (Petasites hybridus L.) is
      clinically efficient in allergic rhinitis (hay fever).

PMID- 12807343
TI  - Long-term efficacy and safety of PRO 160/120 (a combination of sabal and urtica
      extract) in patients with lower urinary tract symptoms (LUTS).

PMID- 12807344
TI  - Effects of a fixed combination of peppermint oil and caraway oil on symptoms and
      quality of life in patients suffering from functional dyspepsia.

PMID- 12807345
TI  - Bacterial deconjugation of arbutin by Escherichia coli.
AB  - Cystinol akut containing arbutin was developed as an antiseptic since it
      liberates hydroquinone in the urine. The in vivo release of hydroquinone from
      arbutin with or without addition of glusulase or an E. coli suspension was
      investigated in 4 volunteers. They ingested 6 dragees Cystinol akut (420 mg
      arbutin equivalent to 168 mg hydroquinone), urine was sampled and assayed by a
      validated HPLC method. RESULTS: In comparison to incubation with glusulase the E.
      coli-suspension resulted in a 2.3 fold higher increase in free hydroquinone. When
      separating bacteria from the urine, the hydroquinone concentration in bacteria
      was 20 fold higher than in the supernatant. CONSEQUENCES: Glucuronic acid or
      sulfuric acid conjugates of hydroquinones obviously are taken up, enriched and
      metabolized to hydroquinone by bacteria. Deconjugation of hydroquinone likely is
      catalyzed by intracellular enzymes presumably present in bacterial cytoplasm;
      comparable activities in eucaryotic cells usually are localized in lysosomes.
      Alkalization of the urine seems not to be a prerequisite to improve the
      antiseptic properties of hydroquinone released from arbutin.

PMID- 12807346
TI  - Dose-response related efficacy in orthostatic hypotension of a fixed combination
      of D-camphor and an extract from fresh crataegus berries and the contribution of
      the single components.
AB  - Independent, double-blinded, randomized, placebo-controlled studies using
      sublingual/oral administration of D-camphor, an extract from fresh crataegus
      berries, and a combination of the two (CCC) yielded the following results: Both
      the D-camphor and the extract from fresh crataegus berries, the components of
      CCC, contribute to the pressoric effects of the combination. The underlying
      hemodynamic mechanisms can be attributed to an increase in total peripheral
      resistance induced by an increased tone of the arterioles with both components
      and the effect of crataegus is intensified by an additional direct positive
      action on cardiac performance. Conceivably, the D-camphor component is the main
      factor in inducing the rapid initial effect, whereas the extract from fresh
      crataegus berries adds a long-lasting effect. For CCC, a dose-dependent increase
      in supine blood pressure and prevention of orthostatic fall in blood pressure
      following tilt table-induced orthostasis in patients with orthostatic
      dysregulation was demonstrated as well. The effect revealed a very rapid onset of
      action within 1 min following administration, confirming the traditional use in
      emergency situations such as orthostatic (pre)syncope. Thus, these studies show
      that CCC, depending on the pressoric activity of its two mono-components, exerts
      a significant effect that counteracts an orthostatic fall in blood pressure and
      thereby provides a rationale for its application that reemphasizes the decades
      long usefulness of this phyto-combination.

PMID- 12807347
TI  - Toxicity of kava pyrones, drug safety and precautions--a case study.
AB  - Kava pyrones have been sold in Germany as OTC anxiolytics until June 2002, when
      all preparations with a kava pyrone content of more than 10(-4) of a homeopathic
      stock solution were withdrawn. Other countries in which kava pyrones have been
      used as anxiolytics, namely GB and the USA, have not followed suit. Kava pyrone
      anxiolytics have been positively reviewed by the Cochrane Collaboration; also
      newer German clinical studies have indicated pharmacological anxiolysis at the
      recommended doses. To use the first choice of treatment, psychotherapy, for all
      uncomplicated cases of pathological fear does not appear to be realistic. Current
      data about kava pyrone toxicity are unclear. Judging from the few well documented
      cases of kava pyrone hepatotoxicity (appr. 2 out of 36) in Germany and
      Switzerland, an immunologically mediated idiosyncratic mechanism appears to be
      most likely, especially at higher doses, whereas a direct toxic mechanism is much
      less likely. No direct results are available for the incidence of kava pyrone
      related adverse drug effects. From spontaneously reported cases the incidences of
      adverse drug reactions cannot be obtained, a rough estimation indicates the
      incidence of hepatotoxicity to be comparable to those of benzodiazepines. Taken
      together, the withdrawal of kava pyrone-based anxiolytics appears to be an ill
      founded over-reaction given the lack of superior therapeutic alternatives.
      Neither the case evaluations presented by the BfArM (Bundesamt fur Arzneimittel
      und Medizinprodukte = Federal Office for Drugs and Medical Products) nor the
      complete rejection of proof for therapeutic efficacy of kava pyrone anxiolytics
      are scientifically well founded.

PMID- 12807348
TI  - Ginkgo extract or cholinesterase inhibitors in patients with dementia: what
      clinical trials and guidelines fail to consider.
AB  - Dementia of Alzheimer's type (DAT), together with vascular dementia, is the most
      important indication for Ginkgo biloba extract (EGb). The therapeutic efficacy of
      this extract is founded on neuroprotective, metabolic and rheological effects. In
      addition to these mechanisms--which also form the basis of the activity of the
      older synthetic nootropics--the hypothesis that DAT is due to a "cholinergic
      deficit" at central synapses has led, over the last decade, to the development of
      a new group of drugs for this indication, the cholinesterase (ChE) inhibitors.
      Thus nowadays, EGb is competing, on the synthetic side, with the ChE inhibitors
      tacrine, donepezil, rivastigmine and galantamine. No direct comparative trials
      have been undertaken, but long-term studies lasting 24-56 weeks to demonstrate
      efficacy have been carried out with both groups of substances in accordance with
      current EU guidelines. To date, only one psychometric scale has gained general
      acceptance as the primary criterion of efficacy, namely the cognitive subscale of
      the Alzheimer's Disease Assessment Scale (ADAS-Cog), whose scores range from 0 to
      70 (the lower the better). The initial scores of patients in the trials were
      between 20 and 30; the improvements after 6 months treatment (less those seen
      with placebo) were about 2 points under Ginkgo extract and 2 to 4 points with the
      ChE inhibitors. However, the relatively small differences are called into
      question by the occurrence of drug-specific side effects with the ChE inhibitors.
      Unlike the treatment with EGb, up to 90% of the patients given the ChE inhibitors
      developed nausea and vomiting, so there is a suspicion that methodological
      reasons in the sense of an "unblinding" of the treatment groups caused the
      apparent superiority in the intensity of the effect. In addition, the benefits of
      treatment were rapidly reversed after ending administration of ChE inhibitors,
      which did not occur to the same extent with EGb. Adverse drug reactions are more
      than 10 times more common with the ChE inhibitors and the treatment costs about
      five times higher than with EGb. Given the limited therapeutic options for DAT,
      treatment with EGb still appears to be the method of choice compared to the ChE
      inhibitors.

PMID- 12807350
TI  - Mechanisms of troglitazone hepatotoxicity.

PMID- 12807351
TI  - Immunomodulatory effects of tetrachlorobenzoquinone, a reactive metabolite of
      hexachlorobenzene.
AB  - Hexachlorobenzene (HCB) is an environmental pollutant that causes autoimmune-like
      effects in humans and rats. It is not completely clear whether T cells are
      involved and, if so, how they are stimulated after oral exposure to HCB. HCB as a
      rather inert chemical is not likely to bind covalently to macromolecules. The
      oxidative metabolite of HCB, tetrachlorobenzoquinone (TCBQ), which is in a redox
      equilibrium with tetrachlorohydroquinone (TCHQ), can bind to macromolecules,
      hence may form hapten-carrier complexes in vivo. We have assessed in the reporter
      antigen-popliteal lymph node assay whether HCB or TCHQ and TCBQ are able to
      induce a 2,4,6-trinitrophenyl (TNP) specific IgG1 response to the T cell
      independent antigen TNP-Ficoll, which is indicative of neoantigen specific T cell
      help. To this end, these compounds and silica were injected into the footpad of
      Balb/c mice. Silica was included as an inert model compound, which causes
      autoimmune-like effects by activating macrophages. Seven days later, cell number
      and TNP specific antibody-secreting cells (ASC) in the popliteal lymph node (PLN)
      were determined. Furthermore, a secondary PLNA was performed to find out if TCHQ
      was capable of eliciting a memory response. Silica, TCHQ, and TCBQ, but not HCB,
      increased PLN cellularity and the number of IgM-producing ASC by ELISPOT. Both
      oxidative metabolites were able to induce the formation of germinal centers as
      assessed by immunohistochemistry and an IgG1 response to TNP-Ficoll. In the
      secondary PLNA, only mice primed with TCHQ and challenged with TCHQ together with
      TNP-Ficoll showed a significant increase in TNP specific IgG1 ASC. Present data
      show that TCHQ and TCBQ are capable of inducing neoantigen specific T cell help
      and that TCHQ can induce a compound specific memory response.

PMID- 12807352
TI  - Conformations of stereoisomeric base adducts to 4-hydroxyequilenin.
AB  - Exposure to estrogen through estrogen replacement therapy increases the risk of
      women developing cancer in hormone sensitive tissues. Premarin (Wyeth), which has
      been the most frequent choice for estrogen replacement therapy in the United
      States, contains the equine estrogens equilin and equilenin as major components.
      4-Hydroxyequilenin (4-OHEN) is a phase I metabolite of both of these substances.
      This catechol estrogen autoxidizes to potent cytotoxic quinoids that can react
      with dG, dA, and dC to form unusual stereoisomeric cyclic adducts (Bolton, J. L.,
      et al. (1998) Chem. Res. Toxicol. 11, 1113-1127). Like other bulky DNA adducts,
      these lesions may exhibit different susceptibilities to DNA repair and mutagenic
      potential, if not repaired in a structure-dependent manner. To ultimately gain
      insights into structure-function relationships, we computed conformations of
      stereoisomeric guanine, adenine, and cytosine base adducts using density
      functional theory. We find near mirror image conformations in stereoisomer adduct
      pairs for each modified base, suggesting opposite orientations with respect to
      the 5' --> 3' direction of the modified strand when the stereoisomer pairs are
      incorporated into duplex DNA. Such opposite orientations could cause stereoisomer
      pairs of lesions to respond differently to DNA replication and repair enzymes.

PMID- 12807353
TI  - Regioselective synthesis of 1,N(2)-etheno-2'-deoxyguanosine and its generation in
      oligomeric DNA.
AB  - Chloroethylene oxide and chloroacetaldehyde, reactive intermediates derived from
      vinyl chloride, and the epoxy-hydroxy-alkanals, produced endogenously in the
      metabolism of polyunsaturated fatty acids, react with nucleic acid bases in DNA
      to form exocyclic etheno derivatives of 2'-deoxyadenosine, 2'-deoxyguanosine, and
      2'-deoxycytidine. This paper describes an efficient method for the synthesis of
      the exocyclic 1,N(2)-etheno adduct of 2'-deoxyguanosine and its incorporation
      into DNA oligomers using automated synthesis techniques. The synthesis was
      initiated by a high-yield alkylation of N(2)-protected 2'-deoxyguanosine at the 1
      position with 1,2-diacetoxy-3-bromopropane. The product was converted to the 5'-O
      dimethoxytrityl-3'-O-phosphoramidite using published techniques and incorporated
      site specifically into DNA oligomers with 99% coupling efficiency. Ring closure
      to yield the 6-hydroxyethano derivative was accomplished by oxidation with sodium
      periodate, and facile dehydration then afforded DNA oligomers containing 1,N(2)
      etheno-2'-deoxyguanosine. All oligomers were characterized fully by
      physicochemical methods.

PMID- 12807354
TI  - Reexamination of the aqueous chemistry of N-Nitroso-3-hydroxymorpholine, a
      metabolite of the carcinogen N-nitrosomorpholine.
AB  - N-Nitroso-3-hydroperoxymorpholine was synthesized in 12 steps starting from a
      commercially available serine derivative and was subsequently characterized by
      elemental analysis, one-dimensional (1)H and (13)C NMR spectroscopy, and
      homonuclear and heteronuclear two-dimensional methods. Treatment of the
      hydroperoxide with triarylphosphine or trialkylphosphine in CD(2)Cl(2) or CD(3)CN
      yields N-nitroso-3-hydroxymorpholine, a putative metabolite of the carcinogen N
      nitrosomorpholine, as indicated by (1)H and (13)C NMR spectroscopy. A study of
      the decomposition of N-nitroso-3-hydroxymorpholine in aqueous buffer solution,
      ionic strength 1 M (KCl), at 25 degrees C is reported. The kinetics of decay obey
      a three term rate law, with terms for a hydrogen ion-dependent, pH-independent,
      and hydroxide ion-dependent reactions, similar to what has been reported for
      other alpha-hydroxynitrosamines. The stability of this compound is similar to
      that of alpha-hydroxynitrosopiperidine reported previously. The reaction of 3
      hydroxymorpholine in aqueous solution, 25 degrees C, pH 6.6, yields (2-hydroxy
      ethoxy)acetaldehyde (62%), acetaldehyde (26%), and glycolaldehyde (26%), based on
      analysis of the dintrophenylhydrazine derivatives. Both the stability and the
      products of decay of N-nitroso-3-hydroxymorpholine that are reported here
      contrast strongly with a previous description.

PMID- 12807355
TI  - Predicting the genotoxicity of thiophene derivatives from molecular structure.
AB  - We report several binary classification models that directly link the genetic
      toxicity of a series of 140 thiophene derivatives with information derived from
      the compounds' molecular structure. Genetic toxicity was measured using an SOS
      Chromotest. IMAX (maximal SOS induction factor) values were recorded for each of
      the 140 compounds both in the presence and in the absence of S9 rat liver
      homogenate. Compounds were classified as genotoxic if IMAX >or= 1.5 in either
      test or nongenotoxic if IMAX < 1.5 for both tests. The molecular structures were
      represented by numerical descriptors that encoded the topological, geometric,
      electronic, and polar surface area properties of the thiophene derivatives. The
      classification models used were linear discriminant analysis (LDA), k-nearest
      neighbor classification (k-NN), and the probabilistic neural network (PNN). These
      were used in conjunction with either a genetic algorithm or a generalized
      simulated annealing to find optimal subsets of descriptors for each classifier.
      The quality of the resulting models was determined by the number of misclassified
      compounds, with preference given to models that produced fewer false negative
      classifications. Model sizes ranged from seven descriptors for LDA to three
      descriptors for k-NN and PNN. Very good classification results were obtained with
      all three classifiers. Classification rates for the LDA, k-NN, and PNN models
      were 80, 85, and 85%, respectively, for the prediction set compounds.
      Additionally, a consensus model was generated that incorporated all three of the
      basic model types. This consensus model correctly predicted the genotoxicity of
      95% of the prediction set compounds.

PMID- 12807356
TI  - Identification of novel electrophilic metabolites of piper methysticum Forst
      (Kava).
AB  - Dietary supplements containing Piper methysticum Forst. (kava) have been
      implicated in multiple cases of liver injury in humans, including 10 recently
      reviewed cases in which patients required liver transplantation following the
      usage of kava-containing products (Centers for Disease Control and Prevention,
      reprinted. (2003) J. Am. Med. Assoc. 289, 36-37). To investigate a possible
      mechanism(s) of kava-induced hepatotoxicity, an extract of kava was incubated in
      vitro with hepatic microsomes, NADPH, and GSH. Electrophilic intermediates that
      were generated via metabolic activation were trapped as GSH conjugates and
      removed from the protein mixture using ultrafiltration. Positive ion electrospray
      LC-MS/MS with precursor ion scanning was used for the selective detection of GSH
      conjugates, and LC-MS(n) product ion scanning was used to elucidate their
      structures. Using this in vitro MS-based screening assay, two novel electrophilic
      metabolites of kava, 11,12-dihydroxy-7,8-dihydrokavain-o-quinone and 11,12
      dihydroxykavain-o-quinone, were identified. Mercapturic acids of these quinoid
      species were not detected in the urine of a human volunteer following ingestion
      of a dietary supplement that contained kava; instead, the corresponding catechols
      were metabolized extensively to glucuronic acid and sulfate conjugates. These
      observations indicate that quinoid metabolites, under most circumstances, are
      probably not formed in substantial quantities following the ingestion of moderate
      doses of kava. However, the formation of electrophilic quinoid metabolites by
      hepatic microsomes in vitro suggests that such metabolites might contribute to
      hepatotoxicity in humans when metabolic pathways are altered (e.g., because of a
      drug interaction, genetic difference in enzyme expression, etc.) or if
      conjugation pathways become saturated.

PMID- 12807358
TI  - Properties of the reaction of chromate with metallothionein.
AB  - The reactivity of chromate or Cr(VI) with rabbit liver metallothionein (MT) was
      explored in this study. Zn(7)-MT reacts very slowly with Cr(VI) in a process
      characterized by a second-order rate constant of 3.9 x 10(-)(4) M(-)(1) s(-)(1).
      During the reaction, Zn(2+) was released from the protein. In contrast, apo-MT
      reduces chromate quicker and in this reaction is much more effective as a
      reducing agent, when compared to Cys or GSH. The kinetics are consistent with a
      reaction pathway involving an initial binding step followed by the reduction of
      Cr(VI). In the process, MT sulfhydryl groups were oxidized at the same rate that
      Cr(VI) disappeared. A Cr(V) intermediate was detected by EPR spectroscopy
      immediately upon mixing apo-MT with Cr(VI). The Cr(V) signal decayed during the
      reaction but was quite stable and could be observed for hours once the supply of
      thiols was depleted. The g values for the Cr(V) species were 2.014 and 1.987. The
      kinetics of the reaction of Cr(VI) and the concentration of the intermediate
      Cr(V) signal were independent of the oxygen concentration and were unaffected by
      the presence of superoxide dismutase, catalase, or DMSO. In the presence of
      oxygen, oxy radicals were generated according to ESR spin-trapping experiments
      with 5,5'-dimethyl-1-pyrroline-N-oxide. Superoxide dismutase decreased and
      catalase or DMSO largely inhibited the formation of the spin-trapped adduct.
      Cr(III), the presumed final species of the Cr(VI) reduction, formed a stable
      complex with apo-MT in the absence of oxygen with an average stoichiometry of two
      Cr ions bound per protein molecule. Upon addition of O(2), the complex slowly
      dissociated.

PMID- 12807357
TI  - Effect of halogenated substituents on the metabolism and estrogenic effects of
      the equine estrogen, equilenin.
AB  - Estrogen replacement therapy has been correlated with an increased risk for
      developing breast and endometrial cancers. One potential mechanism of estrogen
      carcinogenesis involves metabolism of estrogens to 2- and 4-hydroxylated
      catechols, which are further oxidized to electrophilic/redox active o-quinones
      that have the potential to both initiate and promote the carcinogenic process.
      Previously, we showed that the equine estrogens, equilin and equilenin, which are
      major components of the estrogen replacement formulation Premarin (Wyeth-Ayerst),
      are primarily metabolized to the catechol, 4-hydroxyequilenin. This catechol was
      found to autoxidize to an o-quinone causing oxidation and alkylation of DNA in
      vitro and in vivo. To block catechol formation from equilenin, 4-halogenated
      equilenin derivatives were synthesized. These derivatives were tested for their
      ability to bind to the estrogen receptor, induce estrogen sensitive genes, and
      their potential to form catechol metabolites. We found that the 4-fluoro
      derivatives were more estrogenic than the 4-chloro and 4-bromo derivatives as
      demonstrated by a higher binding affinity for estrogen receptors alpha and beta,
      an enhanced induction of alkaline phosphatase activity in Ishikawa cells, pS2
      expression in S30 cells, and PR expression in Ishikawa cells. Incubation of these
      compounds with tyrosinase in the presence of GSH showed that the halogenated
      equilenin compounds formed less catechol GSH conjugates than the parent
      compounds, equilenin and 17beta-hydroxyequilenin. In addition, these halogenated
      compounds showed less cytotoxicity in the presence of tyrosinase than the parent
      compounds in S30 cells. Also, as stated above, the 4-fluoro derivatives showed
      similar estrogenic effects as compared with parent compounds; however, they were
      less toxic in S30 cells as compared to equilenin and 17beta-equilenin. Because
      17beta-hydroxy-4-halogenated equilenin derivatives showed higher estrogenic
      effects than the halogenated equilenin derivatives in vitro, we studied the
      relative ability of the 17beta-hydroxy-4-halogenated equilenin derivatives to
      induce estrogenic effects in the ovariectomized rat model. The 4-fluoro
      derivative showed higher activity than 4-chloro and 4-bromo derivatives as
      demonstrated by inducing higher vaginal cellular differentiation, uterine growth,
      and mammary gland branching. However, 17beta-hydroxy-4-fluoroequilenin showed a
      lower estrogenic activity than 17beta-hydroxyequilenin and estradiol, which could
      be due to alternative pharmacokinetic properties for these compounds. These data
      suggest that the 4-fluoroequilenin derivatives have promise as alternatives to
      traditional estrogen replacement therapy due to their similar estrogenic
      properties with less overall toxicity.

PMID- 12807359
TI  - Comparative identification of prostanoid inducible proteins by LC-ESI-MS/MS and
      MALDI-TOF mass spectrometry.
AB  - Protein identification by MS is well-established. Mixtures of proteins from cell
      extracts are separated by either one- or two-dimensional gel electrophoresis, and
      specific bands or spots are subjected to in-gel digestion and subsequent analysis
      by MS. The two most common types of ionization used in MS are electrospray
      ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). When
      ESI is used, the sample is typically analyzed by inline HPLC-ESI-MS/MS with
      fragmentation of individual digest peptides, followed by database comparison
      between theoretical and experimental fragmentation patterns. MALDI-MS analysis is
      based on peptide mass mapping, with mass measurements of the digest peptides
      searched against a database of theoretical digests. We give here the results of a
      comparison between ESI-ion trap and MALDI-TOF (time-of-flight) analysis of 11
      deoxy,16,16-dimethyl prostaglandin E(2) (DDM-PGE(2)) inducible proteins.
      Individual peptides identified by the two techniques differed, in general, but
      the resulting protein identification was the same. Slightly higher coverage of
      each protein was obtained by MALDI-TOF, but the MS/MS data were more definitive
      by requiring fewer peptides to assign a positive identification. Both methods
      effectively identified two proteins in the same gel band. The samples here are
      derived from a renal epithelial cell line (LLC-PK(1)) established from the New
      Hampshire minipig, a species poorly represented in the current database, and
      strategies and limitations for analyzing such species are discussed.

PMID- 12807360
TI  - Gender differences in microsomal metabolic activation of hepatotoxic clivorine in
      rat.
AB  - The gender differences in the in vitro microsomal metabolic activation of
      hepatotoxic clivorine, a representative naturally occurring hepatotoxic otonecine
      type pyrrolizidine alkaloid, in Sprague-Dawley rats and their relation to the
      gender differences in susceptibility to clivorine intoxication were reported in
      the present study. Clivorine-induced liver damage in the male rat via metabolic
      activation to form the reactive pyrrolic ester followed by covalent binding to
      liver tissue constituents has been reported previously by our research group. The
      present study demonstrated, for the first time, that cytochromes p450 3A1 and
      3A2, which are constitutively expressed in the male rat, might play a significant
      role in the metabolic activation of clivorine in the rat. Thus, in the male rat,
      the metabolic activation by liver microsomes to form the reactive pyrrolic ester
      was found as the only direct metabolic pathway of clivorine followed by
      subsequent formation of the toxic tissue-bound pyrroles leading to
      hepatotoxicity. In the case of the female rat, a less significant metabolic
      activation was observed, whereas the formations of two novel nonpyrrolic
      metabolites were determined as the predominant biotransformations. None of the
      four cDNA-expressed rat enzymes (cytochrome p450 2C12, 2E1, 3A1, 3A2) tested
      could catalyze the formation of these two new metabolites. Furthermore, the
      female rat (LD(50) = 114 +/- 9 mg/kg, i.p.) was found to be significantly less
      susceptible to clivorine intoxication than the male rat (LD(50) = 91 +/- 3 mg/kg,
      i.p.). Therefore, the results suggested that a significantly lower metabolic
      activation due to the lack of cytochrome p450 3A1 and p450 3A2 activities mainly
      accounted for the smaller susceptibility of the female rat to clivorine
      intoxication.

PMID- 12807361
TI  - Binding of perfluorooctanoic acid to rat and human plasma proteins.
AB  - Perfluorooctanoic acid (PFOA) is a commercially important organic fluorochemical
      and is considered to have a long half-life in human blood. In this paper, PFOA
      binding to rat and human plasma proteins was investigated. On the basis of
      results from size-exclusion chromatography and ligand blotting, most PFOA was in
      protein-bound form in male and female rat plasma, and the primary PFOA binding
      protein in plasma was serum albumin. PFOA binding to rat serum albumin (RSA) in
      the gas phase was observed by electrospray ionization MS. (19)F NMR experiments
      revealed that binding to RSA caused peak broadening and chemical shift changes of
      PFOA resonances, and on the basis of this observation, the dissociation constant
      was determined to be approximately 0.3 mM. The dissociation constants for PFOA
      binding to RSA and human serum albumin (HSA) and the numbers of PFOA binding
      sites on RSA and HSA were also determined by a separation method using
      microdesalting columns. No significant difference was found between PFOA binding
      to RSA and PFOA binding to HSA. The dissociation constants for binding of PFOA to
      RSA or HSA and the numbers of PFOA binding sites were in the range of 0.3-0.4 mM
      and 6-9, respectively. On the basis of these binding parameters and the estimated
      plasma concentration of serum albumin, greater than 90% of PFOA would be bound to
      serum albumin in both rat and human blood.

PMID- 12807362
TI  - Synthesis of stereospecifically deuterated 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) iastereomers and metabolism by A/J mouse lung microsomes and
      cytochrome p450 2A5.
AB  - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is a lung carcinogen in mice and rats and is a putative human lung
      carcinogen. NNK undergoes cytochrome p450-mediated metabolic activation to DNA
      binding intermediates but is also extensively reduced to 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanol (NNAL) in vivo. Because NNAL is also tumorigenic, the
      carcinogenicity of NNK may actually be governed by the metabolic activation of
      NNAL, rather than direct activation of NNK. Metabolism of NNK and NNAL at the 4
      position generates the same critical DNA lesion, O(6)-methylguanine, the levels
      of which are correlated to tumorigenicity in the A/J mouse model. In an effort to
      better understand the bioactivation of NNAL and the effect of carbinol-carbon
      stereochemistry on prochiral selectivity at the 4-position, (R)- and (S)-NNAL,
      along with the stereospecifically 4-deuterated diastereomers (1R,4R)-[4
      (2)H(1)]NNAL, (1R,4S)-[4-(2)H(1)]NNAL, (1S,4R)-[4-(2)H(1)]NNAL, and (1S,4S)-[4
      (2)H(1)]NNAL, were synthesized. The in vitro metabolism of these compounds was
      investigated using A/J mouse lung microsomes and Spodoptera frugiperda-expressed
      mouse cytochrome p450 2A5. Carbinol-carbon stereochemistry did not appreciably
      influence stereoselectivity at the 4-position in the metabolism of these
      compounds by mouse lung microsomes or p450 2A5 but did influence the
      regiochemistry of metabolism. The ratio of 4- to N-methyl hydroxylation was
      approximately 1:1 for the A/J mouse lung microsome-mediated metabolism of all
      substrates, but this ratio was higher for (1S) substrates than for their (1R)
      counterparts when p450 2A5 was used. Interestingly, p450 2A5 converted substrates
      with (1S) stereochemistry to the respective N-oxides, but this metabolite was not
      formed from substrates with (1R) stereochemistry. Furthermore, p450 2A5 catalyzed
      the formation of NNK from (1S) substrates at significantly greater maximal rates
      than from (1R) substrates. The implications of these differences in metabolism
      for the tumorigenic mechanism of NNAL are discussed.

PMID- 12807363
TI  - Stereospecific deuterium substitution attenuates the tumorigenicity and
      metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK).
AB  - Stereochemical determinants of the tumorigenicity and metabolism of the tobacco
      specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were
      investigated using the stereospecifically deuterated isotopomers (4R)-[4
      (2)H(1)]NNK and (4S)-[4-(2)H(1)]NNK. Upon ip administration to groups of 20
      female A/J mice, NNK and (4S)-[4-(2)H(1)]NNK exhibited similar lung
      tumorigenicity at three different doses, whereas (4R)-[4-(2)H(1)]NNK was 2-fold
      less tumorigenic at all three doses. In a parallel experiment, levels of O(6)
      methylguanine and 7-methylguanine were 2-fold lower in lung DNA of mice treated
      with (4R)-[4-(2)H(1)]NNK than in mice treated with NNK or (4S)-[4-(2)H(1)]NNK. To
      corroborate these in vivo data, the in vitro metabolism of these compounds was
      investigated using A/J mouse lung microsomes and Spodoptera frugiperda (Sf9)
      expressed mouse cytochrome p450s 2A4 and 2A5. Kinetic isotope effects on the
      apparent V(max) ((D)V) for the product of NNK 4-hydroxylation, OPB, were 2.7 +/-
      0.2 and 2.8 +/- 0.4 when (4R)- and (4S)-[4-(2)H(1)]NNK were incubated with mouse
      lung microsomes, respectively. The (D)V values for OPB formation were 3.2 +/- 0.2
      and 2.2 +/- 0.2 when (4R)-[4-(2)H(1)]NNK was the substrate for p2A4 and 2A5,
      respectively, whereas they were 1.3 +/- 0.1 and 1.1 +/- 0.1 when (4S)-[4
      (2)H(1)]NNK was the substrate for these respective enzymes. Analysis of an OPB
      derivative (10) for deuterium content by LC/MS confirmed the results from the
      kinetic assays and indicated that p450s 2A4 and 2A5 preferentially abstract the
      pro-R 4-hydrogen of NNK. The results obtained using Sf9-expressed p450s provide a
      rationale for the differences observed in the lung tumor and DNA adduct
      experiments, namely, that the attenuated tumorigenicity of (4R)-[4-(2)H(1)]NNK
      relative to (4S)-[4-(2)H(1)]NNK is due to prochiral selectivity during p450
      catalyzed metabolic activation.

PMID- 12807365
TI  - Assessing the economic impact of adverse drug effects.
AB  - Although most commonly used drugs cause adverse effects, some of them with
      potentially serious consequences, relatively little is known about their economic
      impact. The purpose of this review is to summarise information describing the
      cost of treatment of drug-induced adverse effects as an additional cost of
      pharmaceutical treatment. The focus of this study was limited to the overall
      economic impact of drug-related morbidity and to the economic analysis of a
      single class of drugs with different safety profiles. Several studies carried out
      in the US have investigated adverse drug effects experienced by hospitalised
      patients and their impact on hospital costs. Patients who developed adverse
      effects were hospitalised an average of 1.2-3.8 days longer than patients who did
      not, with additional hospital costs of $US2284-5640 per patient (2000 values).
      Other research studies in different countries have quantified the incidence and
      economic consequences of adverse drug effects that occur in the ambulatory
      setting and that generate hospital admission and emergency department visits.
      They have shown that preventable adverse effects constitute between 43.3% and 80%
      of all adverse outcomes leading to emergency visits and hospital admissions, and
      disproportionately increase healthcare costs. Finally, a recent estimation
      revealed that in the US the cost of problems linked to drug use in the ambulatory
      setting exceeded $US177 billion in the year 2000.NSAIDs constitute a widely used
      class of drugs and they are one of the leading drug classes in causing adverse
      effects. The acquisition costs of the drugs, as well as the costs for prevention
      and treatment of adverse effects, determine their cost-effectiveness ratio.
      Depending on the incidence and severity of adverse effects, the cost per adverse
      effect avoided ranges from $US215 to $US35 459 (2000 values). According to the
      contingent valuation methodology, willingness to pay to avoid or reduce the
      incidence of adverse effects is an indicator of the value individuals associate
      with the impact of such effects on their well-being. Individuals are willing to
      pay annually an average of $US240 and $US350, respectively, to avoid vomiting and
      gastrointestinal distress induced by NSAIDs. Although the results of the
      different studies reviewed are not strictly comparable because of differences in
      the severity of adverse effects, the perspective of the analysis, the cost data
      included and the cost component considered, the data show that, apart from the
      implications for health, a substantial quantity of resources are used to treat
      adverse effects.

PMID- 12807366
TI  - The comparative medical costs of atherothrombotic disease in European countries.
AB  - BACKGROUND: The clinical manifestations of atherothrombotic disease include
      ischaemic heart disease (including myocardial infarction [MI]) and
      cerebrovascular disease (including ischaemic stroke [IS]). Although costs
      generated by the clinical manifestations of atherothrombotic disease represent an
      important economic burden for any healthcare system, very few economic
      comparative data are available. OBJECTIVE: To: (i) assess management costs of the
      different practice patterns for acute and chronic phases for MI, IS and
      peripheral arterial disease (PAD) in eight European countries; and (ii) to
      simulate the cost of managing a patient with an atherothrombotic disease for 2
      years in Europe. STUDY PERSPECTIVE: Healthcare system. METHODS: Firstly, the
      medical costs of managing MI and IS were analysed during the acute phase and
      subsequent 6-month periods over a total of 2 years. In each case, a decision tree
      was designed to indicate resource use. Assumptions concerning patient management
      and resource use were based on currently available local and international
      literature, official national statistics and local expert opinions (Delphi
      panel). Costs were assessed using diagnosis-related groups (Austria, Italy,
      Portugal and Sweden), or hospital databases and national tariffs (Belgium,
      France, Spain and Switzerland). Secondly, these costs were correlated to data
      from a large randomised clinical trial to estimate the overall cost per patient
      with atherothrombotic disease over a 2-year period. RESULTS: For MI, there was a
      2-fold difference in costs between the eight countries (euro9512-18 293), with 47
      76% of costs devoted to acute management, 14-48% to follow-up management during
      the first year, and 4-17% to follow-up during the second year. For IS, there was
      a 10-fold difference (euro5607-56 370), with 18-75% devoted to follow-up for the
      years 1995-1997. CONCLUSIONS: There are differences in the overall costs and cost
      breakdown in the clinical management patterns of MI and IS in Europe. These
      differences seem to arise as a result of local treatment pattern specificities as
      well as the availability of specific and well-adapted structures for patients'
      rehabilitation. Further studies are necessary to fully explain these differences.
      The assessment of the total medical costs of managing an atherothrombotic patient
      over a 2-year period (MI, IS, established PAD) has to take into account the risk
      of ischaemic events in different vascular areas (MI, IS or major leg ischaemia).

PMID- 12807364
TI  - Costs of bipolar disorder.
AB  - Bipolar disorder is a chronic affective disorder that causes significant economic
      burden to patients, families and society. It has a lifetime prevalence of
      approximately 1.3%. Bipolar disorder is characterised by recurrent mania or
      hypomania and depressive episodes that cause impairments in functioning and
      health-related quality of life. Patients require acute and maintenance therapy
      delivered via inpatient and outpatient treatment. Patients with bipolar disorder
      often have contact with the social welfare and legal systems; bipolar disorder
      impairs occupational functioning and may lead to premature mortality through
      suicide. This review examines the symptomatology of bipolar disorder and
      identifies those features that make it difficult and costly to treat. Methods for
      assessing direct and indirect costs are reviewed. We report on comprehensive cost
      studies as well as administrative claims data and program evaluations. The
      majority of data is drawn from studies conducted in the US; however, we discuss
      European studies when appropriate. Only two comprehensive cost-of-illness studies
      on bipolar disorder, one prevalence-based and one incidence-based, have been
      reported. There are, however, several comprehensive cost-of-illness studies
      measuring economic burden of affective disorders including bipolar disorder.
      Estimates of total costs of affective disorders in the US range from $US30.4-43.7
      billion (1990 values). In the prevalence-based cost-of-illness study on bipolar
      disorder, total annual costs were estimated at $US45.2 billion (1991 values). In
      the incidence-based study, lifetime costs were estimated at $US24 billion.
      Although there have been recent advances in pharmacotherapy and outpatient
      therapy, hospitalisation still accounts for a substantial portion of the direct
      costs. A variety of outpatient services are increasingly important for the care
      of patients with bipolar disorder and costs in this area continue to grow.
      Indirect costs due to morbidity and premature mortality comprise a large portion
      of the cost of illness. Lost workdays or inability to work due to the disease
      cause high morbidity costs. Intangible costs such as family burden and impaired
      health-related quality of life are common, although it has proved difficult to
      attach monetary values to these costs.

PMID- 12807367
TI  - Economic evaluation of norethisterone acetate/ethinylestradiol (FemHRT) for women
      with menopausal symptoms.
AB  - INTRODUCTION: The objective of this study was to assess the cost effectiveness of
      a continuous combined oral preparation of norethisterone (norethindrone) acetate
      and ethinylestradiol (NA/EE) [FemHRT] as both a first-line and second-line
      therapy for menopausal women. PERSPECTIVE: Third-party payer. METHODS: The cost
      effectiveness of NA/EE was assessed as both a first- and second-line therapy in
      comparison with conjugated equine oestrogen 0.625mg and medroxyprogesterone
      acetate 2.5mg (CEE/MPA) and no therapy. Analysis was conducted within a Markov
      model with states relating to the presence and absence of vaginal bleeding,
      menopausal symptoms and hip fracture. Analysis forecasted life expectancy, QALYs
      and lifetime costs for a 50-year-old menopausal woman. Compliance was modelled
      related to menopausal symptoms and vaginal bleeding. For the base-case analysis,
      it was assumed that compliant women would take therapy for up to 5 years.
      Sensitivity analysis assumed therapy was taken only for 1 year. RESULTS: Compared
      with both CEE/MPA and no therapy, NA/EE led to an increase in both costs and
      QALYs, both as a first- and second-line therapy. For first-line therapy, the
      incremental cost per QALY gained for NA/EE was $2200 Canadian dollars ($Can; 1999
      values) [compared with no therapy] and was $Can20 300 (compared with CEE/MPA).
      For second-line therapy, the incremental cost per QALY gained for NA/EE was
      $Can900 (compared with no therapy) and was $Can16 400 (compared with CEE/MPA).
      Results were robust to most sensitivity analyses. CONCLUSIONS: NA/EE is a cost
      effective therapy for women with menopausal symptoms both as a first-line and
      second-line therapy.

PMID- 12807368
TI  - Direct treatment costs for patients with lung cancer from first recurrence to
      death in france.
AB  - OBJECTIVE: To determine the direct treatment cost of lung cancer management from
      progression to death from the viewpoint of the hospital. METHODS: A retrospective
      descriptive study was performed. Data from 100 patients who died of lung cancer
      and who had received treatment from four different types of hospital were used;
      the hospitals were public hospitals (teaching and non-teaching), private not-for
      profit cancer centres, and private hospitals. Resource utilisation/cost data
      collected included the cost of diagnosis of the recurrence, the cost of
      hospitalisations or day care treatments and ambulatory surgery. All resources
      were valued in 2001 euros. RESULTS: In France, the average cost per patient was
      euro12 518 for the whole group (78% with non-small cell lung cancer [NSCLC], and
      22% with small cell lung cancer [SCLC]), euro13 969 for patients with NSCLC and
      euro7369 for patients with SCLC. The higher cost of treatment in patients with
      NSCLC is explained by longer survival and duration of chemotherapy. In patients
      with NSCLC, 51% of the total cost corresponded to terminal care, with up to seven
      lines of chemotherapy. In patients with SCLC, the costs of diagnosis and terminal
      care each represented 41% of the total cost. CONCLUSIONS: The cost of treatment
      of recurrence of lung carcinoma is high, and is related to the number of lines of
      chemotherapy and the use of radiotherapy and surgery.

PMID- 12807369
TI  - Rescuing patients from the rule of efficiency: a need to debate the 'rule of
      rescue'.

PMID- 12807370
TI  - Meta-analysis of observational studies: the case of rapid-cycling bipolar
      disorder.

PMID- 12807371
TI  - Rapid-cycling bipolar disorder: effects of long-term treatments.
AB  - OBJECTIVE: To compare responses to long-term treatment of rapid-cycling (RC) vs.
      non-RC bipolar disorder patients and assess relative effectiveness of specific
      agents in RC patients. METHOD: Studies identified by literature searching were
      analyzed for effects of RC status and treatment-type on clinical outcome
      (recurrence or non-improvement per exposure-time), using random-effects methods
      to estimate pooled rates and their 95% CI for quantitative meta-analytic
      modeling. RESULTS: Data were obtained from 16 reports with 25 trial-arms
      involving 1856 (905 RC and 951 non-RC) patients treated with carbamazepine,
      lamotrigine, lithium, topiramate, or valproate, alone or with other agents over
      an average of 47.5 months (7347 total patient-years). Estimated RC prevalence was
      15.4%. Crude rates (%/month) of recurrence (2.31/1.20) and clinical non
      improvement (1.93/0.49) averaged 2.9-fold greater in RC vs. non-RC subjects. The
      pooled RC/non-RC risk ratio (RR) for inferior treatment-response (in 13 direct
      comparisons) was 1.40 (CI 1.26-1.56; P < 0.0001). Pooled crude recurrence and non
      improvement rates suggested no clear advantage for any treatment, nor superiority
      for anticonvulsants over lithium. However, only lithium vs. carbamazepine could
      be directly compared (in four treatment-arms) meta-analytically in RC patients
      (RR = 0.93, CI 0.74-1.18, indicating no difference in effectiveness). CONCLUSION:
      As expected, RC was associated with lower effectiveness of all treatments
      evaluated. Direct comparisons of specific treatment alternatives for RC patients
      were rare, and provided no secure evidence of superiority of any treatment.
      Additional long-term studies comparing RC/non-RC patients randomized to specific
      treatments are required.

PMID- 12807372
TI  - Residual symptoms in elderly major depression remitters.
AB  - OBJECTIVE: To assess residual symptoms in severe geriatric major depression in
      remission, and to determine baseline clinical and sociodemographic predictors of
      residual symptoms in remitters. METHOD: A total of 108 elderly patients with
      unipolar major depression were evaluated and treated naturalistically for 9
      months so as to record the predictors of residual symptoms in remitters. In order
      to reduce the likelihood of confusing residual symptoms with normal effects of
      age, 30 control subjects were also monitored. RESULTS: Seventy-nine patients
      (73.1%) were considered remitters and 82.3% of remitters showed residual
      symptoms. Medical burden, chronic stress and subjective social support were the
      only variables which predicted the severity of residual symptoms in remitters.
      CONCLUSION: Residual symptoms in elderly patients with major depression in
      remission should not only be attributed exclusively to intrinsic factors of the
      illness or the age of the individual patient, but also to external factors.

PMID- 12807373
TI  - A differential response to nortriptyline and fluoxetine in melancholic
      depression: the importance of age and gender.
AB  - OBJECTIVE: To consider the impact of age and gender on the antidepressant
      response to nortriptyline and fluoxetine in melancholic depression. METHOD: Of
      191 depressed patients, 113 met study criteria for melancholia. All patients were
      randomized to receive either fluoxetine or nortriptyline. Response rates, defined
      as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale
      over 6 weeks of antidepressant treatment on an intention to treat basis, were
      examined by age, and by age and gender. RESULTS: Melancholic depressed patients
      40 years or older, especially men, had a markedly superior response to
      nortriptyline compared with fluoxetine. Conversely, melancholic depressed
      patients, age 18-24 years, especially women, had a markedly superior response to
      fluoxetine. CONCLUSION: Age and gender appear to be critical variables in
      understanding differential antidepressant responses to tricyclic antidepressants
      and selective serotonin reuptake inhibitors in melancholic depression.

PMID- 12807374
TI  - Antidepressants: psychiatrists' opinions and clinical practice.
AB  - OBJECTIVE: To describe and compare psychiatrists' opinion on antidepressant drugs
      and their prescriptions to depressed patients. METHOD: Between January and
      September 1999 a representative sample of French psychiatrists was asked their
      opinion of the 15 most prescribed antidepressants, and then to describe the
      treatments of the current depressive episode of four depressive patients each,
      their changes and the reason thereof. RESULTS: A total of 232 psychiatrists and
      935 patients participated. The best ranked antidepressants were clomipramine,
      paroxetine and amitriptyline for efficacy, tianeptine, paroxetine and citalopram
      for tolerability. In patients, the most often prescribed were paroxetine,
      fluoxetine and venlafaxine. Those least often stopped for intolerance were
      tianeptine (2.9%), citalopram (5.2%), venlafaxine (3.3%) and amitriptyline (5.7%)
      for lack of efficacy. There was no difference in stopping rates for inefficacy of
      tricyclics and serotonin-selective agents. CONCLUSION: The best predictors for
      the prescribed antidepressants were the psychiatrists' overall rankings and
      opinions of the tolerability of the drug.

PMID- 12807375
TI  - The Danish PET/depression project: cognitive function and regional cerebral blood
      flow.
AB  - OBJECTIVE: To clarify the relationship between cognitive functions and regional
      cerebral blood flow (rCBF) in a large group of depressed patients compared with
      healthy controls. METHOD: A set of principal components was extracted from scores
      of a battery of neuropsychological tests of 40 patients suffering from major
      depression and 49 healthy controls. The components were correlated by multiple
      linear regression analyses to selected regions of interest in the brain obtained
      from positron emission tomography images. RESULTS: In contrast to findings in the
      healthy controls, cognitive functions in the depressed patients correlated
      significantly with rCBF in specified regions of interest in only a few instances.
      CONCLUSION: Our study indicates that disturbed cognitive functions in depression
      do not relate to specific areas of the brain in the same way as normal cognitive
      functioning, suggesting that the abnormalities of brain function in major
      depression may be qualitative, rather than quantitative, in nature.

PMID- 12807376
TI  - Affective disorders in neurological diseases: a case register-based study.
AB  - OBJECTIVE: To investigate the temporal relationships between a range of
      neurological diseases and affective disorders. METHOD: Data derived from linkage
      of the Danish Psychiatric Central Register and the Danish National Hospital
      Register. Seven cohorts with neurological index diagnoses and two control group
      diagnoses were followed for up to 21 years. The incidences of affective disorders
      in the different groups were compared with the control groups, using competing
      risks to consider the risk of affective disorder and the risk of death in the
      same analysis. RESULTS: We found an increased incidence of affective disorders in
      dementia, Parkinson's disease, epilepsy, stroke and intracerebral haemorrhage
      compared with control groups. The association was found to be the strongest for
      dementia and Parkinson's disease. In hospitalized patients, with incident
      multiple sclerosis, the incidence of affective disorder was lower than the
      incidence in the control groups. CONCLUSION: In neurological diseases there seems
      to be an increased incidence of affective disorders. The elevated incidence was
      found to be particularly high for dementia and Parkinson's disease
      (neurodegenerative diseases).

PMID- 12807377
TI  - EEG phenotype in alcoholism: increased coherence in the depressive subtype.
AB  - OBJECTIVE: Electroencephalography (EEG) power and coherence changes may be trait
      markers for alcoholism providing clues to brain mechanisms of vulnerability.
      However, it is unclear whether alpha power and coherence differences reflect
      reversible toxic or withdrawal effects of alcohol. METHOD: The EEGs of 10 non
      abstinent and 16 long-term abstinent alcoholics (7.7 +/- 5.8 years) and 25
      controls were analyzed. Levels of anxiety and depression were assessed by
      questionnaire. RESULTS: No statistically significant EEG power differences were
      observed between groups, although the numerical difference between alcoholics and
      controls was similar to that previously reported. Bilateral, intrahemispheric,
      posterior coherences were significantly increased in the alpha and beta frequency
      bands both in long-term abstinent and non-abstinent alcohol-dependent subjects -
      particularly when depressiveness was included as a covariate. CONCLUSION: These
      results suggest that increased EEG-coherence (cortical synchronization) may serve
      as endophenotype for alcoholism in conjunction with increased depressiveness and
      point to a possible involvement of GABAergic and/or glutamatergic
      neurotransmission.

PMID- 12807378
TI  - Evaluation of the PAHO/WHO training program on the detection and treatment of
      depression for primary care nurses in Panama.
AB  - OBJECTIVE: This study evaluated the efficacy of a training program developed by
      Pan American Health Organization/World Health Organization (PAHO/WHO) for primary
      care nurses aimed at improving their capacity to detect and manage depression.
      METHOD: Changes in knowledge and clinical practice were assessed in a group of
      primary care nurses in Panama who underwent the program. They were compared with
      a group of controls. RESULTS: Nurses who underwent the training program showed a
      statistically significant improvement in knowledge and detection of depressive
      disorders. In addition, they increased their notification of patients with
      depression to the primary care physician. No change was noted in the control
      group. CONCLUSION: The results point to the benefit of the PAHO/WHO training
      program for primary care nurses in the care of major depression. Further studies
      are required to confirm these results.

PMID- 12807379
TI  - Explanatory models of psychosis among community health workers in South India.
AB  - OBJECTIVE: To examine commonly held indigenous beliefs about mental illness,
      which often differ markedly from the biomedical models, among community health
      workers in rural South India. METHOD: Indigenous beliefs about chronic psychosis
      were elicited from community health workers. The Short Explanatory Model
      Interview formed the basis of the interview. RESULTS: A variety of indigenous
      beliefs, which contradicted the biomedical model, were elicited. A significant
      proportion of health workers did not recognize chronic psychosis as a disease
      condition, believing that it was caused by black magic, evil spirits and poverty,
      and felt that doctors could not help. CONCLUSION: The results of the study
      suggest that training programmes should elicit and discuss local beliefs prior to
      the teaching of the biomedical model of mental disorders.

PMID- 12807380
TI  - Sertraline-induced hypomania: a genuine side-effect.
AB  - OBJECTIVE: Antidepressants including selective serotonin reuptake inhibitor
      (SSRI)-associated mania or hypomania has been well documented in the literature
      but these patients with switch have either mood disorders or various risk factors
      for bipolar disorder. This case report examines SSRI-induced hypomania in a
      patient with dissociative disorder and highlights hypomania as a genuine side
      effect of sertraline rather than a switch. METHOD: A 23-year-old female patient
      with dissociative disorder has been described. RESULTS: Hypomanic symptoms
      emerged during treatment with sertraline at the dose of 50 mg/day after 3-4 days
      of initiation of therapy and had complete recovery within 7 days after stopping
      sertraline. CONCLUSION: In the absence of risk factors for manic switch,
      sertraline-induced hypomania may be a true side-effect of drug.

PMID- 12807381
TI  - Somatoform pain disorder: a valid diagnosis?

PMID- 12807382
TI  - Clozapine and pulmonary embolism.

PMID- 12807386
TI  - A double-blind randomized clinical trial in amyotrophic lateral sclerosis using
      lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid
      levels and clinical parameters.
AB  - OBJECTIVES: A study was conducted to examine the effect of lamotrigine (LTG) in
      amyotrophic lateral sclerosis (ALS). MATERIAL AND METHODS: Patients were entered
      in a double-blind, placebo-controlled, crossover study. None of the patients were
      treated with riluzole, which was not approved for treatment of ALS in Sweden when
      the study started. After randomization, each patient was treated with placebo or
      LTG 300 mg daily, followed by a washout period and a second treatment period.
      RESULTS: Thirty patients completed the study and were included in the analysis of
      the primary outcome, which was measured with clinical scales. The cerebrospinal
      fluid (CSF) levels of glutamate, aspartate, branched-chain amino acids and LTG
      were also measured. Changes for glutamate, valine and LTG were found during the
      progression of the disease. The clinical parameters and the levels of CSF amino
      acids were similar for the two treatment groups. CONCLUSION: No clinical effect
      of LTG on ALS progression could be found.

PMID- 12807387
TI  - A pooled analysis of adjunctive topiramate in refractory partial epilepsy.
AB  - OBJECTIVES: To evaluate the impact of different dosages of topiramate (TPM) add
      on to stable antiepileptic therapy for refractory partial epilepsy in adults.
      MATERIAL AND METHODS: Pooled intention-to-treat analysis of six similarly
      designed double-blind, placebo-controlled trials, including 481 patients treated
      with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving
      placebo. RESULTS: Seizures were reduced by >/=50% from baseline in 41% of TPM
      treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%,
      respectively, were seizure-free (P < 0.003). TPM was significantly better than
      placebo regardless of gender, age, baseline seizure rate as well as number and
      type of concomitant antiepileptic drugs. Efficacy was statistically significant
      in favour of TPM at all dose levels: at least 50% seizure reduction was achieved
      in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800
      mg TPM when compared with 15% with placebo (P </= 0.001 for each dosage arm vs
      placebo). The median reduction in monthly seizure frequency was 38%, 42%, 45% and
      38% vs 8%, respectively (P </= 0.001). Moreover, response to TPM was
      significantly superior to placebo at each of the dose levels tested for most of
      the baseline variables. The total percentage of withdrawals increased with the
      dosage, and the withdrawals caused by adverse events increased from 3% with
      placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM
      (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003).
      CONCLUSION: The efficacy of TPM add-on in partial epilepsy is consistent across
      efficacy endpoints and independent of study population characteristics. The
      response at 200 mg TPM is similar to the response at higher doses, but as drop
      outs caused by adverse events are more frequent above the 200 mg dose, this
      pooled analysis supports that 200 mg daily is a good target dose for add-on
      therapy in most patients with partial epilepsy, showing an excellent balance
      between efficacy and tolerability.

PMID- 12807388
TI  - Native and transformed alpha2-macroglobulin in plasma from patients with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease with unknown
      etiology. Various proteinases have been observed in increased levels in the
      central nervous system of patients with MS, which may contribute to the release
      of immunogenic myelin components. alpha2-Macroglobulin (alpha2M) inhibits a broad
      spectrum of proteinases sterically, undergoing major conformational changes
      induced by the proteinases themselves. Moreover, alpha2M acts as a carrier of
      several cytokines in the systemic circulation. By use of radial immunodiffusion,
      we determined the total alpha2M levels in plasma from 28 MS patients and 15
      control subjects [14 patients with other neurologic diseases (OND) and one
      healthy individual]. No significant differences in total alpha2M concentration
      were observed between the MS patients and the control subjects. A comparison of
      the degree of alpha2M transformation in MS patients with different disease
      courses and controls was performed, using monoclonal antibodies (mAbs) specific
      for binding to native and transformed alpha2M, respectively. The fractions of
      transformed alpha2M were significantly increased in patients with secondary or
      primary progressive disease course compared with the controls. No significant
      differences were obtained using a native-specific mAb. At least a major
      proportion of alpha2M from the MS patients was able to change conformation from
      its native to its transformed state, as demonstrated by a shift in mAb
      reactivity, following methylamine treatment of the plasma samples. In conclusion,
      the results indicate that plasma alpha2M may be inactivated at a higher degree in
      patients with chronic progressive MS compared with patients with OND. This may
      influence the levels of proteinases and cytokines in the systemic circulation and
      may furthermore have diagnostic implications.

PMID- 12807389
TI  - Inclusion body myositis--sensory dysfunction revealed with quantitative
      determination of somatosensory thresholds.
AB  - In order to evaluate sensory function in inclusion body myositis (IBM), nine
      patients were subjected to sensibility screening and quantitative determination
      of somatosensory thresholds. Data were compared with results from
      electrophysiological examination and muscle biopsy. On sensibility screening all
      but one of the IBM patients had abnormal findings in hands and/or feet mostly
      affecting thermal sensibility. Vibratory thresholds were abnormal in five and
      thermal thresholds in four of the patients. Mean vibratory thresholds were
      significantly (P < 0.05) higher in the IBM patients when compared with the
      controls. Significantly increased heat pain thresholds were found in hands and
      feet when compared with the controls while thermal thresholds were normal. Nerve
      conduction velocities were decreased in three patients, EMG showed both myopathic
      and neuropathic abnormalities in six patients. Eight patients had neuropathic
      abnormalities on muscle biopsy. The sensory dysfunction found suggests an
      affection of peripheral nerves in IBM mainly affecting large diameter myelinated
      nerve fibres corroborating earlier findings of a peripheral neuropathy in IBM.

PMID- 12807390
TI  - Gender differences in disability and health-related quality of life in patients
      with Parkinson's disease treated with stereotactic surgery.
AB  - OBJECTIVES: To investigate eventual differences between women and men with
      Parkinson's disease (PD) before and after surgery, with respect to clinical
      status, disability and health-related quality of life (HRQoL). MATERIAL AND
      METHODS: Twenty-four men and 14 women with PD received a total of 46 surgical
      procedures (pallidotomy, thalamotomy and deep brain stimulation of the thalamus,
      pallidum or subthalamic nucleus). The impact of PD on disability and other
      aspects of HRQoL was analysed separately in men and women before and at a mean of
      11 months after surgery, using the following assessment tools: The Unified
      Parkinson's Disease Rating Scale (UPDRS), the ADL Taxonomy, the Nottingham Health
      Profile, the Life Satisfaction Questionnaire and a Visual Analogue Scale.
      RESULTS: At surgery, women had a significantly longer duration of disease than
      men (mean: 15 vs. 10 years, P < 0.01). They had a higher stage on the Hoehn and
      Yahr scale and worse scores on UPDRS parts II (ADL) and IV (complications), as
      well as on the Schwab and England scale and on the ADL Taxonomy. Following
      surgery, both men and women showed improvement, but women experienced greater
      benefit than men in ADL, in emotions, and in social life. CONCLUSIONS: Perhaps
      women with PD should be offered surgery more often and earlier in the course of
      their disease.

PMID- 12807391
TI  - An adjustable CSF shunt: advices for clinical use.
AB  - OBJECTIVES: The opening pressure and the resistance of a CSF shunt are essential
      for clinical use in order to set the proper opening pressure and to determine the
      shunt function in vivo. We find it of vital importance to validate and supplement
      the product description given by the manufacturer. The in vitro properties of a
      newly introduced, adjustable differential pressure valve with a siphon-preventing
      device (Strata valve) was compared with its predecessor (Delta valve). METHODS:
      An automated, computerized experimental set-up based on regulation of pressure,
      built into an incubator at 37 degrees C, was used. Opening pressure, resistance
      and siphon preventing properties were determined. Six brand-new shunts of each
      type with catheters were tested. The Delta valves were at a performance level of
      1.5. RESULTS: The hydrodynamic properties of the Strata and Delta valves were
      similar. The anti-siphoning device was functioning for all valves. The estimated
      mean resistance for Delta and Strata shunts was 2.6 +/- 0.4 and 2.2 +/- 1.0
      mmHg/ml/min, respectively. The mean opening pressure for the five performance
      levels of the Strata shunt are: 3.3, 5.1, 7.7, 10.7 and 13.1 mmHg. There may
      however, be considerable variations between the shunts. CONCLUSIONS: The Strata
      shunt is a properly working adjustable valve with anti-siphoning device that
      showed good reproducibility concerning opening pressure and resistance. At
      performance level 1.5, the new Strata shunt was similar to its predecessor
      concerning opening pressure and resistance. The given values of the different
      opening pressures and resistance could be used for in vivo testing of the valve
      function with a standard lumbar CSF infusion test.

PMID- 12807392
TI  - Dural metastasis in patients with malignant neoplasm and chronic subdural
      hematoma.
AB  - OBJECTIVES: Dural metastasis associated with chronic subdural hematoma (CSH) is
      rare in patients with malignant neoplasm. In this study, biopsy of the dura and
      cytological examination of the subdural hematoma was performed for patients with
      malignant neoplasm and chronic subdural hematoma to investigate the association
      of dural metastasis and CSH. MATERIALS AND METHODS: Four patients with malignant
      neoplasm (one breast, one lung, and one colon cancers, and one lymphoma) were
      diagnosed with CSH. Biopsy of the dura and cytological examination of the
      subdural fluid were performed for each of these patients. RESULTS: Pathological
      examination of the dura revealed metastasis for two patients (one lymphoma and
      one breast cancer), with no specific change except neomembrane formation revealed
      for the dura of the other two patients. The cytology study was negative for all
      four patients. All these four patients died within 10 days of the operation; one
      from recurrent subdural hematoma, and three from infection. CONCLUSION: The
      results suggest that dural metastasis should be considered in patients with
      malignant neoplasm and CSH. Further, the prognosis for patients with malignant
      neoplasm and CSH may be poor because of systemic metastasis and the side-effects
      of chemotherapy.

PMID- 12807393
TI  - Caveolin-3 gene mutation in Japanese with rippling muscle disease.
AB  - OBJECTIVES: Rippling muscle disease (RMD) is a rare myopathy characterized by
      percussion-induced rapid muscle contractions, muscle mounding, and rippling.
      Recently a caveolin-3 gene (CAV3) mutation was identified in patients with
      autosomal dominant RMD. The objective of this study was to determine whether a
      similar mutation was present in two Japanese families with this condition.
      PATIENTS AND METHODS: Clinical examination, mutational analysis, and muscle
      immunohistochemistry were carried out in six patients from two Japanese RMD
      pedigrees. RESULTS: Apart from the atrophy of the intrinsic muscles in their
      hands and a slight muscle weakness in their fingers, the clinical features of our
      patients were compatible with RMD. Our investigation revealed a CAV3 missense
      mutation, i.e. Arg26Gln in both families. Immunohistochemistry performed on a
      muscle biopsy specimen showed reduced caveolin-3 surface expression. CONCLUSIONS:
      Japanese RMD also appears to result from a CAV3 mutation.

PMID- 12807394
TI  - Detection of acute thalamo-mesencephalic infarction: diffusion abnormality
      precedes T2 hyperintensity.
AB  - OBJECTIVE: To examine the time course of signal changes in diffusion-weighted
      magnetic resonance imaging (DW-MRI) and T2-weighted MRI in a case of cerebral
      infarction in the posterior circulation territory. MATERIALS AND METHODS:
      Diffusion- and T2-weighted MRI and comparison of signal changes in these
      sequences at 4 h, 1 day and 4 days after the onset of clinical symptoms caused by
      acute thalamo-mesencephalic infarction. RESULTS: Four hours after the onset of
      symptoms, signal changes in DW-MRI revealed an infarction in the territory of the
      posterior perforating thalamic artery, whereas no signal changes were detected in
      T2-weighted MRI. In follow-up MRI 1 and 4 days after infarction, however, a
      marked hyperintensity matching the location of the diffusion deficit could be
      identified in T2 images. CONCLUSION: Signal changes in DW-MRI precede T2
      hyperintensity after infarction in the posterior circulation territory after
      hemispheric infarction.

PMID- 12807395
TI  - Benign bilateral independent periodic lateralized epileptiform discharges.
AB  - Bilateral independent periodic lateralized epileptiform discharges (BIPLEDs)
      usually appear transiently in patients with severe disturbances of consciousness
      and are indicative of a poor prognosis. Recurrent BIPLEDs have not previously
      been reported in the literature. We report a 64-year-old patient with bilateral
      hippocampal lesions (cerebral infarction) who exhibited persistent periodic
      lateralized epileptiform discharges (PLEDs) (chronic PLEDs) associated with
      recurrent BIPLEDs. Electroencephalography was recorded for more than 6 months.
      Left hemispheric PLEDs appeared first. Next, PLEDs shifted to the right
      hemisphere and BIPLEDs occasionally developed. Brain magnetic resonance imaging
      and single-photon emission computed tomography with technetium-99-hexamethyl
      propyleneamine oxime was performed before and after the appearance of BIPLEDs.
      The patient had no remarkable clinical symptoms aside from mild memory impairment
      for this period of time. This is the first case of recurrent 'benign' BIPLEDs,
      that is, BIPLEDs with a positive prognosis.

PMID- 12807396
TI  - MR evaluation of crossed and uncrossed cerebral-cerebellar diaschisis.
AB  - In three patients with infantile hemiplegia syndrome, MR imaging done later in
      life showed significant volume loss in the cerebellar hemisphere contralateral to
      the side of the affected cerebrum in two and ipsilateral in one. By comparison,
      the cerebellar volume loss seemed to correlate with the degree of volume loss in
      the contralateral cerebral hemispheres in two patients. These observations
      provide morphological evidence of the phenomenon of crossed and
      uncrossed/ipsilateral cerebral cerebellar diaschisis (CCD and ICD). Functional
      neuroimaging studies in support of the concept of CCD and ICD have been
      critically reviewed in the light of the morphological changes demonstrated in the
      cases cited herein.

PMID- 12807397
TI  - Levodopa-induced hyperhomocysteinaemia in Parkinson's disease.

PMID- 12807399
TI  - Infant lightness perception: do 4-month-old infants follow Wallach's ratio rule?
AB  - When adults view a test disk embedded in a higher-luminance surround, the
      perceived lightness of the disk is largely determined by the surround-to-disk
      (S/D) luminance ratio (Wallach's ratio rule). Performance of 4-month-old infants
      tested with a forced-choice novelty-preference technique was consistent with
      predictions based on Wallach's ratio rule. This result suggests that the ability
      to extract and maintain information about local luminance ratios is present early
      in infancy. This ability is likely to contribute to the development of lightness
      constancy.

PMID- 12807400
TI  - Directional bias in the mental representation of spatial events: nature or
      culture?
AB  - Previous research has shown a tendency for people to imagine simple sentences as
      evolving from left to right, with the sentence subject being located to the left
      of the object. In two cross-cultural studies comparing Italian and Arab
      participants, we investigated whether this bias is a function of hemispheric
      specialization or of directionality of written language (left to right in
      Italian, right to left in Arabic). Both studies found a reversal of directional
      bias in Arabs. Italians tended to position the subject to the left of the object,
      and Arabs tended to position the subject to the right of the object (Experiment
      1); both groups were facilitated in a sentence-picture matching task when the
      subject was drawn in the position that it would usually occupy in the written
      language (left for Italians, right for Arabs; Experiment 2). In Experiment 2, an
      additional, language-independent facilitation was observed when action evolved
      from left to right, suggesting that both hemispheric specialization and scanning
      habit affect visual imaging.

PMID- 12807401
TI  - The body-inversion effect.
AB  - Researchers argue that faces are recognized via the configuration of their parts.
      An important behavioral finding supporting this claim is the face-inversion
      effect, in which inversion impairs recognition of faces more than nonface
      objects. Until recently, faces were the only class of objects producing the
      inversion effect for untrained individuals. This study investigated whether the
      inversion effect extends to human body positions, a class of objects whose
      exemplars are structurally similar to each other. Three experiments compared the
      recognition of upright and inverted faces, houses, and body positions using a
      forced-choice, same/different paradigm. For both reaction time and error data,
      the recognition of possible human body postures was more affected by inversion
      than the recognition of houses. Further, the recognition of possible human body
      postures and recognition of faces showed similar effects of inversion. The
      inversion effect was diminished for impossible body positions that violated the
      biomechanical constraints of human bodies. These data suggest that human body
      positions, like faces, may be processed configurally by untrained viewers.

PMID- 12807402
TI  - Sit-and-wait strategies in dynamic visual search.
AB  - The role of memory in visual search has lately become a controversial issue.
      Horowitz and Wolfe (1998) observed that performance in a visual search task was
      little affected by whether the stimuli were static or randomly relocated every
      111 ms. Because a memory-based mechanism, such as inhibition of return, would be
      of no use in the dynamic condition, Horowitz and Wolfe concluded that memory is
      likewise not involved in the static condition. However, Horowitz and Wolfe could
      not effectively rule out the possibility that observers adopted a different
      strategy in the dynamic condition than in the static condition. That is, in the
      dynamic condition observers may have attended to a subregion of the display and
      waited for the target to appear there (sit-and-wait strategy). This hypothesis is
      supported by experimental data showing that performance in their dynamic
      condition does not differ from performance in another dynamic condition in which
      observers are forced to adopt a sit-and-wait strategy by being presented with a
      limited region of the display only.

PMID- 12807403
TI  - Effect of social category priming on personal attitudes.
AB  - In four studies, we examined the spontaneous activation of specific attitudes
      related to social categories. These studies investigated whether priming
      participants with concepts associated with the elderly and skinheads influenced
      participants' attitudes. The results consistently demonstrated that priming a
      social category can influence people's attitudes such that they become more
      similar to those of people in the primed category. After participants were primed
      with the elderly category, their attitudes became more conservative; after
      participants were primed with the skinhead category, their attitudes became more
      prejudiced. We also found that these effects can occur without awareness and
      intention and are specific to the participants' own attitudes. The theoretical
      and practical implications of these findings are considered.

PMID- 12807404
TI  - Providing social support may be more beneficial than receiving it: results from a
      prospective study of mortality.
AB  - This study examines the relative contributions of giving versus receiving support
      to longevity in a sample of older married adults. Baseline indicators of giving
      and receiving support were used to predict mortality status over a 5-year period
      in the Changing Lives of Older Couples sample. Results from logistic regression
      analyses indicated that mortality was significantly reduced for individuals who
      reported providing instrumental support to friends, relatives, and neighbors, and
      individuals who reported providing emotional support to their spouse. Receiving
      support had no effect on mortality once giving support was taken into
      consideration. This pattern of findings was obtained after controlling for
      demographic, personality, health, mental health, and marital-relationship
      variables. These results have implications for understanding how social contact
      influences health and longevity.

PMID- 12807405
TI  - Context effects in word recognition: evidence for early interactive processing.
AB  - This study investigated whether a prior context influenced lexical access as
      indexed by participants' electrophysiological response in the N1 from 132 to 192
      ms poststimulus. Ambiguous, high-frequency (HF), and low-frequency (LF) words
      were presented in neutral and biasing contexts. Event-related potentials (ERPs)
      for ambiguous words were compared with those for unambiguous HF (word form) and
      LF (word meaning) control words. Word frequency effects in the N1 extended
      previous ERP findings. A marginal effect of context for LF words provided
      electrophysiological support for the context-by-frequency interaction shown in
      reaction time paradigms. In neutral context, responses to ambiguous words were
      comparable to responses to HF words, and in biasing context (where context
      instantiated the subordinate sense), responses to ambiguous words were comparable
      to responses to LF words. The results establish temporal parameters for the early
      operation of context in lexical access. These constraints are more consistent
      with an interactive than a modular account.

PMID- 12807406
TI  - Using nonconscious behavioral mimicry to create affiliation and rapport.
AB  - Nonconscious behavioral mimicry occurs when a person unwittingly imitates the
      behaviors of another person. This mimicry has been attributed to a direct link
      between perceiving a behavior and performing that same behavior. The current
      experiments explored whether having a goal to affiliate augments the tendency to
      mimic the behaviors of interaction partners. Experiment 1 demonstrated that
      having an affiliation goal increases nonconscious mimicry, and Experiment 2
      further supported this proposition by demonstrating that people who have
      unsuccessfully attempted to affiliate in an interaction subsequently exhibit more
      mimicry than those who have not experienced such a failure. Results suggest that
      behavioral mimicry may be part of a person's repertoire of behaviors, used
      nonconsciously, when there is a desire to create rapport.

PMID- 12807407
TI  - Voluntary head movement and allocentric perception of space.
AB  - Although visual input is egocentric, at least some visual perceptions and
      representations are allocentric, that is, independent of the observer's vantage
      point or motion. Three experiments investigated the visual perception of three
      dimensional object motion during voluntary and involuntary motion in human
      subjects. The results show that the motor command contributes to the objective
      perception of space: Observers are more likely to apply, consciously and
      unconsciously, spatial criteria relative to an allocentric frame of reference
      when they are executing voluntary head movements than while they are undergoing
      similar involuntary displacements (which lead to a more egocentric bias).
      Furthermore, details of the motor command are crucial to spatial vision, as
      allocentric bias decreases or disappears when self-motion and motor command do
      not match.

PMID- 12807408
TI  - Overactive action monitoring in obsessive-compulsive disorder: evidence from
      functional magnetic resonance imaging.
AB  - The anterior cingulate cortex (ACC) in patients with obsessive-compulsive
      disorder (OCD) has been found to be hyperactive at rest, during symptom
      provocation, and after commission of errors in cognitive tasks. This
      hyperactivity might reflect an abnormality in conflict detection, a hypothesized
      basic mechanism for the action-monitoring function of the ACC. This hypothesis
      was tested using functional magnetic resonance imaging, by scanning 11 OCD
      patients and 13 matched control subjects while they performed a version of the
      continuous-performance task with four trial types that induced graded levels of
      response conflict. Although a behavioral index of conflict (i.e., accuracy) was
      similar for patients and control subjects, the ACC activation was increased in
      patients during high-conflict trials. The error-related activity in the same
      brain region was also higher in patients, consistent with previous
      electrophysiological findings. Both conflict- and error-related activity showed
      trends for positive correlations with severity of OCD symptoms, but not with
      anxiety. These findings suggest that as part of an overactive action-monitoring
      system, the ACC is more directly involved in the pathophysiology of OCD than
      previously thought.

PMID- 12807409
TI  - Evidence of motor planning in infant reaching behavior.
AB  - When adults reach for an object, kinematic measures of their approach movement
      are affected by what they intend to do after grasping it. We examined whether
      such future intended actions would be reflected in the approach-to-grasp phase of
      infant reaching. Twenty-one 10-month-old infants were encouraged to either throw
      a ball into a tub or fit it down a tube. Kinematic measures of the approach phase
      of the reach toward the ball were obtained using a motion analysis system.
      Infants, like adults, reached for the ball faster if they were going to
      subsequently throw it as opposed to using it in the precision action. The
      perceptual aspects of the ball were the same and cannot account for these
      kinematic differences. Infants appear to be planning both segments of their
      actions in advance. Our findings provide evidence for a level of sophistication
      in infant motor planning not reported before.

PMID- 12807410
TI  - Visual motion influences the contingent auditory motion aftereffect.
AB  - In this study, we show that the contingent auditory motion aftereffect is
      strongly influenced by visual motion information. During an induction phase,
      participants listened to rightward-moving sounds with falling pitch alternated
      with leftward-moving sounds with rising pitch (or vice versa). Auditory
      aftereffects (i.e., a shift in the psychometric function for unimodal auditory
      motion perception) were bigger when a visual stimulus moved in the same direction
      as the sound than when no visual stimulus was presented. When the visual stimulus
      moved in the opposite direction, aftereffects were reversed and thus became
      contingent upon visual motion. When visual motion was combined with a stationary
      sound, no aftereffect was observed. These findings indicate that there are strong
      perceptual links between the visual and auditory motion-processing systems.

PMID- 12807411
TI  - The "ticktock" of our internal clock: direct brain evidence of subjective accents
      in isochronous sequences.
AB  - The phenomenon commonly known as subjective accenting refers to the fact that
      identical sound events within purely isochronous sequences are perceived as
      unequal. Although subjective accenting has been extensively explored using
      behavioral methods, no physiological evidence has ever been provided for it. In
      the present study, we tested the notion that these perceived irregularities are
      related to the dynamic deployment of attention. We disrupted listeners'
      expectancies in different positions of auditory equitone sequences and measured
      their responses through brain event-related potentials (ERPs). Significant
      differences in a late parietal (P3-like) ERP component were found between the
      responses elicited on odd-numbered versus even-numbered positions, suggesting
      that a default binary metric structure was perceived. Our findings indicate that
      this phenomenon has a rather cognitive, attention-dependent origin, partly
      affected by musical expertise.

PMID- 12807412
TI  - Semantic categorization in the human brain: spatiotemporal dynamics revealed by
      magnetoencephalography.
AB  - We examined the cortical representation of semantic categorization using magnetic
      source imaging in a task that revealed both dissociations among superordinate
      categories and associations among different base-level concepts within these
      categories. Around 200 ms after stimulus onset, the spatiotemporal correlation of
      brain activity elicited by base-level concepts was greater within than across
      superordinate categories in the right temporal lobe. Unsupervised clustering of
      data showed similar categorization between 210 and 450 ms mainly in the left
      hemisphere. This pattern suggests that well-defined semantic categories are
      represented in spatially distinct, macroscopically separable neural networks,
      independent of physical stimulus properties. In contrast, a broader, task
      required categorization (natural/man-made) was not evident in our data. The
      perceptual dynamics of the categorization process is initially evident in the
      extrastriate areas of the right hemisphere; this activation is followed by higher
      level activity along the ventral processing stream, implicating primarily the
      left temporal lobe.

PMID- 12807413
TI  - Nonverbal "accents": cultural differences in facial expressions of emotion.
AB  - We report evidence for nonverbal "accents," subtle differences in the appearance
      of facial expressions of emotion across cultures. Participants viewed photographs
      of Japanese nationals and Japanese Americans in which posers' muscle movements
      were standardized to eliminate differences in expressions, cultural or otherwise.
      Participants guessed the nationality of posers displaying emotional expressions
      at above-chance levels, and with greater accuracy than they judged the
      nationality of the same posers displaying neutral expressions. These findings
      indicate that facial expressions of emotion can contain nonverbal accents that
      identify the expresser's nationality or culture. Cultural differences are
      intensified during the act of expressing emotion, rather than residing only in
      facial features or other static elements of appearance. This evidence suggests
      that extreme positions regarding the universality of emotional expressions are
      incomplete.

PMID- 12807414
TI  - The effect of object and event orientation on perception of biological motion.
AB  - Detection and recognition of point-light walking is reduced when the display is
      inverted, or turned upside down. This indicates that past experience influences
      biological motion perception. The effect could be the result of either presenting
      the human form in a novel orientation or presenting the event of walking in a
      novel orientation, as the two are confounded in the case of walking on feet. This
      study teased apart the effects of object and event orientation by examining
      detection accuracy for upright and inverted displays of a point-light figure
      walking on his hands. Detection of this walker was greater in the upright
      display, which had a familiar event orientation and an unfamiliar object
      orientation, than in the inverted display, which had a familiar object
      orientation and an unfamiliar event orientation. This finding supports accounts
      of event perception and recognition that are based on spatiotemporal patterns of
      motion associated with the dynamics of an event.

PMID- 12807415
TI  - Character strengths before and after September 11.
AB  - Did Americans change following the September 11 terrorist attacks? We provide a
      tentative answer with respect to the positive traits included in the Values in
      Action Classification of Strengths and measured with a self-report questionnaire
      available on-line and completed by 4,817 respondents. When scores for individuals
      completing the survey in the 2 months immediately after September 11 were
      compared with scores for those individuals who completed the survey before
      September 11, seven character strengths showed increases: gratitude, hope,
      kindness, leadership, love, spirituality, and teamwork. Ten months after
      September 11, these character strengths were still elevated, although to a
      somewhat lesser degree than immediately following the attacks.

PMID- 12807416
TI  - Reading disappearing text: cognitive control of eye movements.
AB  - Participants read sentences containing high- or low-frequency target words under
      normal reading conditions or disappearing-text conditions (in which the word that
      was fixated disappeared after 60 ms). Even though the fixated word had
      disappeared after 60 ms, there was still a robust frequency effect wherein
      readers fixated longer on low-frequency words than on high-frequency words. Thus,
      the results are consistent with cognitive-control models of eye movement control
      and inconsistent with visual/oculomotor-control models. Although the uptake of
      visual information is clearly important for reading, it is the cognitive
      processes associated with understanding the fixated words that drive the eyes
      through the text.

PMID- 12807419
TI  - Selenium and selenoproteins in the brain and brain diseases.
AB  - Over the past three decades, selenium has been intensively investigated as an
      antioxidant trace element. It is widely distributed throughout the body, but is
      particularly well maintained in the brain, even upon prolonged dietary selenium
      deficiency. Changes in selenium concentration in blood and brain have been
      reported in Alzheimer's disease and brain tumors. The functions of selenium are
      believed to be carried out by selenoproteins, in which selenium is specifically
      incorporated as the amino acid, selenocysteine. Several selenoproteins are
      expressed in brain, but many questions remain about their roles in neuronal
      function. Glutathione peroxidase has been localized in glial cells, and its
      expression is increased surrounding the damaged area in Parkinson's disease and
      occlusive cerebrovascular disease, consistent with its protective role against
      oxidative damage. Selenoprotein P has been reported to possess antioxidant
      activities and the ability to promote neuronal cell survival. Recent studies in
      cell culture and gene knockout models support a function for selenoprotein P in
      delivery of selenium to the brain. mRNAs for other selenoproteins, including
      selenoprotein W, thioredoxin reductases, 15-kDa selenoprotein and type 2
      iodothyronine deiodinase, are also detected in the brain. Future research
      directions will surely unravel the important functions of this class of proteins
      in the brain.

PMID- 12807420
TI  - Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor
      knockout mice.
AB  - The role of serotonin (5-HT)1B receptors in the mechanism of action of selective
      serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo
      microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout
      (KO 5-HT1B) mice in order to compare the effects of chronic administration of
      paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on
      extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral
      hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral
      hippocampus, approximately 20 h after removing the minipump, were not altered by
      chronic paroxetine treatment in both genotypes. On day 15, in the ventral
      hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger
      increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This
      difference between the two genotypes in the effect of the paroxetine challenge
      persisted following chronic paroxetine treatment. Conversely, in the medial
      prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in
      saline-pretreated mice of both genotypes. Such a challenge produced a further
      increase in cortical [5-HT]ext compared with that in saline-pretreated groups of
      both genotypes, but no differences were found between genotypes following chronic
      treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 micro m
      paroxetine was perfused locally through the dialysis probe implanted in the
      ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in
      acutely or chronically treated wild-type mice. Systemic administration of the
      mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated
      wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext
      in the ventral hippocampus, whereas systemic administration of the selective 5
      HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of
      quantitative microdialysis in the medial prefrontal cortex and ventral
      hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and
      the extraction fraction of 5-HT were similar in the medial prefrontal cortex and
      ventral hippocampus of both genotypes, suggesting that no compensatory response
      to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT
      uptake capacity occurred in vivo. As steady-state brain concentrations of
      paroxetine at day 14 were similar in both genotypes, it is unlikely that
      differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are
      due to alterations of the drug's pharmacokinetic properties in mutants. These
      data suggest that there are differences between the ventral hippocampus and
      medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their
      role in regulating dialysate 5-HT levels. These presynaptic receptors retain
      their capacity to limit 5-HT release mainly in the ventral hippocampus following
      chronic paroxetine treatment in mice.

PMID- 12807421
TI  - Mitogen and stress response kinase-1 (MSK1) mediates excitotoxic induced death of
      hippocampal neurones.
AB  - Activation of the mitogen-activated protein kinase (MAPK/ERK) signal transduction
      pathway may mediate excitotoxic neuronal cell death in vitro and during ischemic
      brain injury in vivo. However, little is known, of the upstream regulation or
      downstream consequences of ERK activation under these conditions. Magnesium
      removal has been described to induce hyperexcitability and degeneration in
      cultured hippocampal neurones. Here, we show that neurotoxicity evoked by Mg2+
      removal in primary hippocampal neurones stimulates ERK, but not p38,
      phosphorylation. Removal of Mg2+ also resulted in induction of the MAPK/ERK
      substrate mitogen- and stress-response kinase 1 (MSK1) and induced
      phosphorylation of the MSK1 substrate, the transcription factor cAMP response
      element binding protein (CREB). Neuronal death and phosphorylation of components
      in this cascade were inhibited by the Raf inhibitor SB-386023, by the MEK
      inhibitor U0126, or by the MSK1 inhibitors H89 and Ro318220. Importantly, this
      form of cell death was inhibited in hippocampal neurones cultured from MSK1-/-
      mice and inhibitors of Raf or MEK had no additive neuroprotective effect.
      Together, these data indicate that MSK1 is a physiological kinase for CREB and
      that this activity is an essential component of activity-dependent neuronal cell
      death.

PMID- 12807422
TI  - Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of
      DA and NMDA receptor antagonists vary as a function of neuronal phenotype and
      environmental context.
AB  - Dopamine (DA) and glutamate neurotransmission is thought to be critical for
      psychostimulant drugs to induce immediate early genes (IEGs) in the caudate
      putamen (CPu). We report here, however, that the ability of DA and glutamate NMDA
      receptor antagonists to attenuate amphetamine-evoked c-fos mRNA expression in the
      CPu depends on environmental context. When given in the home cage, amphetamine
      induced c-fos mRNA expression predominately in preprodynorphin and
      preprotachykinin mRNA-containing neurons (Dyn-SP+ cells) in the CPu. In this
      condition, all of the D1R, D2R and NMDAR antagonists tested dose-dependently
      decreased c-fos expression in Dyn-SP+ cells. When given in a novel environment,
      amphetamine induced c-fos mRNA in both Dyn-SP+ and preproenkephalin mRNA
      containing neurons (Enk+ cells). In this condition, D1R and non-selective NMDAR
      antagonists dose-dependently decreased c-fos expression in Dyn-SP+ cells, but
      neither D2R nor NR2B-selective NMDAR antagonists had no effect. Furthermore,
      amphetamine-evoked c-fos expression in Enk+ cells was most sensitive to DAR and
      NMDAR antagonism; the lowest dose of every antagonist tested significantly
      decreased c-fos expression only in these cells. Finally, novelty-stress also
      induced c-fos expression in both Dyn-SP+ and Enk+ cells, and this was relatively
      resistant to all but D1R antagonists. We suggest that the mechanism(s) by which
      amphetamine evokes c-fos expression in the CPu varies depending on the stimulus
      (amphetamine vs. stress), the striatal cell population engaged (Dyn-SP+ vs. Enk+
      cells), and environmental context (home vs. novel cage).

PMID- 12807423
TI  - L-DOPA supply to the neuro retina activates dopaminergic communication at the
      early stages of embryonic development.
AB  - DOPA decarboxylase (DDC; aromatic-l-amino acid decarboxylase; EC 4.1.1.28) is
      absent in retinas from 6-day-old chicken embryos (E6) but is expressed in retina
      of E8 embryos, in the presumptive outer plexiform layer. Thereafter, DDC appears
      in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10
      and E15/16 retinas, pre-incubated with l-DOPA for 1 h, increased 250- and 600
      fold, respectively, showing that DDC is active since early in development.
      Intercellular communication, measured by endogenous cyclic AMP accumulation, was
      observed when retinas from E9/10 to E15/16 were pre-incubated for 1 h with 1 mm l
      DOPA, washed and followed by incubation in the presence of 0.5 mm 3-isobutyl-1
      methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was
      prevented when pre-incubation with l-DOPA was carried out in the presence of
      carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2
      micro m). The incubation of retinas in medium previously conditioned by retina
      pigmented epithelium (RPE) also increased its cyclic AMP content with the
      characteristics described for l-DOPA. Our results show that dopaminergic
      communication takes place in the embryonic retina, before tyrosine hydroxylase
      expression, provided l-DOPA is supplied to the tissue. It also shows that RPE is
      a potential source of l-DOPA early in development.

PMID- 12807424
TI  - The heterogeneous growth cone glycoprotein gp93 is identical to the signal
      regulatory protein SIRPalpha/SHPS-1/BIT.
AB  - Growth cone gp93 is a highly heterogeneous membrane glycoprotein with an Mr of
      about 93 kDa. It was purified from adult rat brain and microsequenced. The
      sequences of four different peptide fragments of gp93 matched those of the
      'signal regulatory protein' SIRPalpha (also known as SHPS-1, BIT or P84), an Ig
      superfamily member. SIRPalpha contains a cytoplasmic tail that is a tyrosine
      kinase substrate and binds the protein tyrosine phosphatase SHP-2. SIRPalpha and
      gp93 also were immunochemically cross-reactive. A PCR strategy was used to
      determine whether gp93/SIRPalpha heterogeneity in the brain depended upon the
      presence of different transcripts and, thus, sequence heterogeneity. However, we
      observed only a single full-length transcript. A short splice variant also was
      detected. These data identify gp93 as the Ig superfamily member SIRPalpha.
      Together with our previous results, the data also demonstrate that, in rat brain,
      gp93/SIRPalpha heterogeneity is the result of differential glycosylation (plus
      phosphorylation), rather than sequence heterogeneity.

PMID- 12807425
TI  - The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic
      acid-induced hippocampal injury: evidence for a compensatory effect by increased
      CCR2 and CCR3.
AB  - Chemokines and their receptors have been strongly implicated in the inflammatory
      process. However, their roles in excitotoxic brain injury are largely unknown. In
      this study we used C-C chemokine receptor 5 (CCR5) knockout (KO) mice to
      investigate the role of CCR5 in neurodegeneration induced by intranasal
      administration of the excitotoxin kainic acid (KA). Although KA treatment
      resulted in an increased CCR5 mRNA level in the hippocampi of wild-type mice, a
      CCR5 deficiency in KO mice did not affect either the clinical and pathological
      changes in vivo or the neuronal susceptibilities to KA insult in vitro. KA
      treatment stimulated mRNA expression of the monocyte chemoattractant protein-2
      (MCP-2) in both the wild-type and KO mice. KA treatment did not affect mRNA
      levels for the macrophage inflammatory protein-1alpha (MIP-1alpha) or the
      regulated upon activation normal T cells expressed and secreted protein (RANTES)
      in either wild-type or CCR5 KO mice. CCR2 mRNA expression was undetectable in the
      hippocampi of wild-type mice regardless of KA treatment. In contrast, CCR5 KO
      mice showed CCR2 mRNA expression that was remarkably increased after KA
      treatment. KA treatment did not affect CCR3 mRNA expression in the wild-type
      mice, whereas KO mice showed both a higher basal level of CCR3 mRNA expression as
      well as a strong upregulation following KA treatment. These results indicate that
      CCR5 is not a necessary inflammatory mediator in KA induced neurodegeneration.
      The roles of CCR5 in excitotoxic injury in CCR5 deficient mice are compensated by
      increased CCR2 and CCR3 expression, which share the common MCP-2 ligand with
      CCR5.

PMID- 12807426
TI  - Valproic acid inhibits substance P-induced activation of protein kinase C epsilon
      and expression of the substance P receptor.
AB  - The neuropeptide substance P (SP) has been hypothesized to be involved in the
      etiopathology of affective disorders. This hypothesis is based on the findings
      that neurokinin-1-receptor antagonists have antidepressant effects in depressed
      patients and that SP may worsen mood. In this study, we investigated the effect
      of the mood-stabilizing agents valproic acid (VPA), carbamazepine, and lithium on
      SP-induced gene expression. As a model system, we used primary rat astrocytes and
      human astrocytoma cells, which both express functional SP-receptors and, upon
      stimulation with SP, synthesize interleukin-6 (IL-6), a cytokine which has been
      shown to be elevated during the acute depressive state. We found that VPA dose
      dependently inhibited SP-induced IL-6 synthesis which was seen with pre
      incubation periods of 30 min, 3, 7 and 14 days, whereas carbamazepine and lithium
      showed no inhibitory effect. The inhibitory effect of VPA was not mediated by
      inhibition of the stress-regulated kinases p38 and p42/44 (Erk1/2) but by
      inhibition of protein kinase C epsilon activation. Furthermore, VPA down
      regulated the expression of the substance P receptor (neurokinin(NK)-1-receptor)
      as assessed by real-time PCR. Whether both mechanisms contribute to the mood
      stabilizing properties of VPA has to be evaluated in further studies.

PMID- 12807427
TI  - Subcellular distributions of rat CaM kinase phosphatase N and other members of
      the CaM kinase regulatory system.
AB  - Ca2+/Calmodulin-dependent protein kinase (CaM kinase) regulatory system is
      composed of multifunctional CaM kinases such as CaM kinases IV and I, upstream
      CaM kinases such as CaM kinase kinases alpha and beta, which activate
      multifunctional CaM kinases, and CaM kinase phosphatases such as CaM kinase
      phosphatase and CaM kinase phosphatase N, which deactivate the activated
      multifunctional CaM kinases. To understand the combinations of CaM kinases I and
      IV, CaM kinase kinases alpha and beta, and CaM kinase phosphatases, the locations
      of the enzymes in the cell were examined by immunocytochemical studies of
      cultured cells. The results indicate that CaM kinase I, CaM kinase kinase beta,
      and CaM kinase phosphatase occur in the cytoplasm and that CaM kinase IV, CaM
      kinase kinase alpha (and CaM kinase kinase beta in some cell types and tissues),
      and CaM kinase phosphatase N occur inside the cellular nucleus, suggesting that
      there are at least two different sets of CaM kinase regulatory systems, one
      consisting of CaM kinase I, CaM kinase kinase beta, and CaM kinase phosphatase in
      the cytoplasm and the other consisting of CaM kinase IV, CaM kinase kinase alpha
      (and CaM kinase kinase beta in some cell types and tissues), and CaM kinase
      phosphatase N in the nucleus.

PMID- 12807428
TI  - Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a
      phosphatidylinositol 3-kinase (PI3) kinase-dependent manner in Neuro2a cells.
AB  - Insulin signalling is well studied in peripheral tissue, but not in neuronal
      tissue. To gain more insight into neuronal insulin signalling we examined protein
      kinase B (PKB) and extracellular regulated kinase 1 and 2 (ERK1/2) regulation in
      serum-deprived Neuro2a cells. Insulin phosphorylated PKB in a dose-dependent
      manner but reduced phosphorylation of ERK1/2. Both processes were
      phosphatidylinositol 3-kinase (PI3K) dependent. Interestingly, blockade of PI3K
      in combination with insulin induced phosphorylation of ERK1/2. The
      phosphorylation of ERK1/2 could be blocked with a specific inhibitor of mitogen
      activated protein/ERK kinase (MEK), suggesting that it was mediated through the
      highly conserved Ras-Raf-MEK-ERK1/2 pathway. Prolonged exposure to high
      concentrations of insulin resulted in a desensitized PI3K-PKB route. The insulin
      induced inhibition of ERK1/2 phosphorylation was also diminished when the PI3K
      PKB route was desensitized. Blockade of PI3K in combination with insulin,
      however, still resulted in an unaltered MEK-dependent phosphorylation of ERK1/2.
      We conclude that PI3K is an important integrator of insulin signalling in Neuro2a
      cells as it regulates activation of PKB and inhibition of ERK1/2, and is
      sensitive to the duration of the insulin stimulus.

PMID- 12807429
TI  - Inhibition of NMDA-induced striatal dopamine release and behavioral activation by
      the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.
AB  - Our laboratory has previously shown that the synthetic neuroactive steroid 3alpha
      hydroxy-5beta-pregnan-20-one hemisuccinate (3alpha5betaHS) is a negative
      modulator of NMDA receptors in vitro. Similarly, 3alpha5betaHS exhibits rapid
      sedative, analgesic, anticonvulsive, and neuroprotective effects in vivo. Here we
      report a study designed to investigate whether a negatively charged neuroactive
      steroid, 3alpha5betaHS, modulates the action of NMDA receptors in vivo. Our
      results indicate that peripherally administered 3alpha5betaHS enters the CNS and
      inhibits NMDA-mediated motor activity and dopamine release in the rat striatum.
      The increase in motor activity induced by intrastriatal microinjection of NMDA
      was blocked by the systemic administration of 3alpha5betaHS and the NMDA-induced
      increase in extracellular dopamine in the striatum was also attenuated by both
      systemically administered and intrastriatally administered (by in vivo
      microdialysis) 3alpha5betaHS. These data indicate that 3alpha5betaHS acts through
      striatal NMDA receptors in vivo. When taken together, these results suggest that
      neuroactive steroids may prove to be effective in the treatment of neurological
      and psychiatric disorders involving over-stimulation of NMDA receptors in the
      mesotelencephalic dopamine system.

PMID- 12807430
TI  - Escalation of cocaine self-administration does not depend on altered cocaine
      induced nucleus accumbens dopamine levels.
AB  - Previous studies showed that prolonged access to cocaine or heroin self
      administration (long access, or LgA) produces an escalation in drug intake not
      observed with limited access to the drug (short access, or ShA). The present
      experiment employed in vivo microdialysis to test the role of alterations in drug
      pharmacokinetics and/or efficacy in increasing dopamine (DA) levels in the
      nucleus accumbens (NAcc) during cocaine intake escalation. In experiment 1, both
      ShA and LgA rats were challenged with passive intravenous administration of
      cocaine (0.125-1 mg/injection). Regardless of the doses tested, there was no
      difference between groups in the ability of cocaine to increase NAcc DA levels
      and no group differences in the temporal profile of dialysate cocaine levels. In
      experiment 2, cocaine and DA concentrations were measured during cocaine self
      administration. Self-administration produced sustained increases of DA in the
      NAcc with LgA rats maintaining greater steady levels of DA (750% of baseline)
      than ShA rats (400% of baseline). The difference in the LgA versus ShA rats was
      not due to differences in the efficacy of cocaine to elevate DA levels, or in the
      rate of cocaine metabolism, but was directly related to the amount of self
      administered cocaine. These findings show that changes in cocaine efficacy or
      pharmacokinetics do not play a critical role in cocaine intake escalation.

PMID- 12807431
TI  - Pro-apoptotic signaling in neuronal cells following iron and amyloid beta peptide
      neurotoxicity.
AB  - In a previous report, we characterized several oxidative stress parameters during
      the course of amyloid beta (Abeta) peptide/Fe2+-induced apoptotic death in
      neuronal cells. In extending these findings, we now report a marked decrease in
      protein kinase C (PKC) isoforms, reduced Akt serine/threonine kinase activity,
      Bcl 2-associated death promoter (BAD) phosphorylation and enhanced p38 mitogen
      activated protein kinase (MAPK) and caspase-9 and -3 activation, 12 h after
      addition of both 5 micro m Abeta and 5 micro m Fe2+. These activities reminiscent
      for a pro-apoptotic cellular course were blocked in the presence of the iron
      chelator deferroxamine. Abeta alone, increased PKC isoform levels between three-
      and four-fold after 12 h, enhanced Akt activity approximately eight-fold and
      Ser136 BAD phosphorylation two-fold, suggesting that by itself is not toxic. Fe2+
      alone transiently enhanced p38 MAPK and caspase-9 and -3 enzymes indicative for
      cell damage, but was not sufficient to cause cell death as previously indicated.
      GF, a PKC inhibitor or wortmannin, a blocker of the Akt pathway enhanced
      Abeta/Fe2+-induced toxicity, while SB, a p38 MAPK inhibitor, prevented cell
      damage and apoptosis. These findings further support the hypothesis that metal
      ion chelation and inhibitors of pro-apoptotic kinase cascades may be beneficial
      for Alzheimer's disease therapy.

PMID- 12807432
TI  - Tumour necrosis factor-related apoptosis-inducing ligand sequentially activates
      pro-survival and pro-apoptotic pathways in SK-N-MC neuronal cells.
AB  - The SK-N-MC neuroblastoma cell line, which expresses surface tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R2 and TRAIL-R4,
      was used as a model system to examine the effect of TRAIL on key intracellular
      pathways involved in the control of neuronal cell survival and apoptosis. TRAIL
      induced distinct short-term (1-60 min) and long-term (3-24 h) effects on the
      protein kinase B (PKB)/Akt (Akt), extracellular signal-regulated kinase (ERK),
      cAMP response element-binding protein (CREB), nuclear factor kappa B (NF-kappaB)
      and caspase pathways. TRAIL rapidly (from 20 min) induced the phosphorylation of
      Akt and ERK, but not of c-Jun NH2-terminal kinase (JNK). Moreover, TRAIL
      increased CREB phosphorylation and phospho-CREB DNA binding activity in a
      phosphatidylinositol 3-kinase (PI 3K)/Akt-dependent manner. At later time points
      (from 3 to 6 h onwards) TRAIL induced a progressive degradation of inhibitor of
      kappaB (IkappaB)beta and IkappaBepsilon, but not IkappaBalpha, coupled to the
      nuclear translocation of NF-kappaB and an increase in its DNA binding activity.
      In the same time frame, TRAIL started to activate caspase-8 and caspase-3, and to
      induce apoptosis. Remarkably, caspase-dependent cleavage of NF-kappaB family
      members as well as of Akt and CREB proteins, but not of ERK, became prominent at
      24 h, a time point coincident with the peak of caspase-dependent apoptosis.

PMID- 12807433
TI  - Distribution, levels, and activation of MEK1 in Alzheimer's disease.
AB  - Extracellular-signal-regulated kinase (ERK) has been implicated in the
      pathogenesis of Alzheimer's disease (AD), but the upstream cascade leading to ERK
      activation has not been elucidated. In this study, we focused on one of the
      physiological activators of ERK, mitogen-activated protein kinase (MAPK)/ERK
      kinase 1 (MEK1). Although there was no significant difference in the level and
      distribution of total MEK1 between AD and age-matched control cases, increased
      levels of activated phospho-MEK1 were specifically localized to neuronal
      intracytoplasmic granular structures in severe AD (Braak stage V-VI). The
      considerable overlap between MEK1 and its downstream effector, phospho-ERK,
      suggests both a functional and mechanistic link. Nuclear localization of phospho
      MEK1 was a prominent feature in both mild AD cases (Braak stage III-IV) and
      control cases with limited pathology (Braak stage I-II). Since MEK1 is normally
      cytoplasmic due to the active export from nucleus because of the presence of
      nuclear export signal in its amino-terminus, we suspect that the apparent nuclear
      accumulation of phospho-MEK1 in AD patients at early stages suggests that
      abnormal nuclear trafficking may contribute to the pathogenesis of AD. By
      immunoblot analyses, phospho-MEK1 was significantly increased in AD over control
      cases. Together, these findings lend further credence to the notion that the ERK
      pathway is dysregulated in AD and also indicate an active role for this pathway
      in disease pathogenesis.

PMID- 12807434
TI  - Dopamine-dependent cytotoxicity of tetrahydrobiopterin: a possible mechanism for
      selective neurodegeneration in Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disorder associated with selective
      loss of dopaminergic neurons in the substantia nigra. While the underlying cause
      of this cell death is poorly understood, oxidative stress is thought to play a
      role. We have previously shown that tetrahydrobiopterin (BH4), an obligatory co
      factor for tyrosine hydroxylase (TH), exerts selective toxicity on dopamine
      producing cells and that this is prevented by antioxidants. This study shows that
      BH4-induced dopaminergic cell death is primarily mediated by dopamine, evidenced
      by findings that (i) BH4 toxicity is increased in proportion to cellular dopamine
      content; (ii) non-dopaminergic cells become susceptible to BH4 upon exposure to
      dopamine; and (iii) depletion of dopamine attenuates BH4 toxicity in dopamine
      producing cells. BH4 causes lipid peroxidation, suggesting involvement of
      oxidative stress but the toxicity does not require enzymatic oxidation of
      dopamine. Instead, it seems to involve formation of quinone product(s) because
      (i) the cell death is attenuated by exposure to or induction of quinone reductase
      and (ii) BH4-treated cells show increased formation of protein-bound quinones,
      which is inhibited by thiol antioxidants. These data taken together suggest that
      the presence of both BH4 and dopamine is important in rendering dopaminergic
      cells vulnerable and that this involves formation of reactive dopamine quinone
      products.

PMID- 12807435
TI  - Regulation of ania-6 splice variants by distinct signaling pathways in striatal
      neurons.
AB  - The striatum is a brain region involved in motor control and in diverse forms of
      implicit memory. It is also involved in the pathogenesis of many significant
      human disorders, including drug addiction, that are thought to involve adaptive
      changes in gene expression. We have previously shown that the cyclin L, ania-6,
      is expressed as at least two splice forms, which are differentially regulated in
      striatal neurons by different neurotransmitters. Here, we report that ania-6
      transcription is mostly regulated via cAMP response element binding protein
      (CREB), but that signaling pathways that converge on CREB at the transcriptional
      level produce different effects on splicing and neuronal gene expression.
      Glutamate induced a long ania-6 mRNA that encodes a truncated form of the cyclin.
      This effect depended on the activation of NMDA receptors but was independent of
      both calcium/calmodulin-dependent protein kinases (CaMK) and extracellular
      regulated kinase (ERK). Forskolin or brain-derived neurotropic factor (BDNF)
      induced a short ania-6 mRNA, that encodes the full-length cyclin, and this
      induction depended on ERK. However, KCl-mediated induction of ania-6 short mRNA,
      which required activation of L-type calcium channels, was independent of ERK but
      depended on CaMK. These data suggest that different neuronal signals can
      differentially regulate splicing and that different intracellular pathways can be
      recruited to yield a given splice variant.

PMID- 12807436
TI  - Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans
      overexpressing human alpha-synuclein.
AB  - Overexpression of human alpha-synuclein in model systems, including cultured
      neurons, drosophila and mice, leads to biochemical and pathological changes that
      mimic synucleopathies including Parkinson's disease. We have overexpressed both
      wild-type (WT) and mutant alanine53-->threonine (A53T) human alpha-synuclein by
      transgenic injection into Caenorhabditis elegans. Motor deficits were observed
      when either WT or A53T alpha-synuclein was overexpressed with a pan-neuronal or
      motor neuron promoter. Neuronal and dendritic loss were accelerated in all three
      sets of C. elegans dopaminergic neurons when human alpha-synuclein was
      overexpressed under the control of a dopaminergic neuron or pan-neuronal
      promoter, but not with a motor neuron promoter. There were no significant
      differences in neuronal loss between overexpressed WT and A53T forms or between
      worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate
      neuronal and behavioral perturbations elicited by human alpha-synuclein in C.
      elegans that are dependent upon expression in specific neuron subtypes. This
      transgenic model in C. elegans, an invertebrate organism with excellent
      experimental resources for further genetic manipulation, may help facilitate
      dissection of pathophysiologic mechanisms of various synucleopathies.

PMID- 12807437
TI  - Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on
      prostaglandin E2 release in primary rat microglia.
AB  - Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a
      variety of pathophysiological situations such as head trauma, ischemia or
      Alzheimer's disease. Most of these protective actions have been attributed to the
      antioxidative capacity of ascorbic acid. Besides the presence of elevated levels
      of oxygen radicals, prostaglandins produced by neurones and microglial cells seem
      to play an important role in prolonged tissue damage. We investigated whether
      ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment
      the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis.
      Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide
      treated primary rat microglial cells (IC50 = 3.70 micro m). In combination with
      acetylsalicylic acid (IC50 = 1.85 micro m), ascorbic acid augmented the
      inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 micro m
      in combination with 100 micro m ascorbic acid). Ascorbic acid alone or in
      combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2)
      protein synthesis but inhibited COX-2 enzyme activity. Our results show that
      ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2
      synthesis, which may help to explain a possible protective effect of ascorbic
      acid in various brain diseases.

PMID- 12807438
TI  - Gene expression in human neural stem cells: effects of leukemia inhibitory
      factor.
AB  - Human neural precursor cells grown in culture provide a source of tissue for drug
      screening, developmental studies and cell therapy. However, mechanisms underlying
      their growth and differentiation are poorly understood. We show that epidermal
      growth factor (EGF) responsive precursors derived from the developing human
      cortex undergo senescence after 30-40 population doublings. Leukemia inhibitory
      factor (LIF) increased overall expansion rates, prevented senescence and allowed
      the growth of a long-term self renewing neural stem cell (ltNSCctx) for up to 110
      population doublings. We established basal gene expression in ltNSCctx using
      Affymetrix oligonucleotide microarrays that delineated specific members of
      important growth factor and signaling families consistently expressed across
      three separate lines. Following LIF withdrawal, 200 genes showed significant
      decreases. Protein analysis confirmed LIF-regulated expression of glial
      fibrillary acidic protein, CD44, and major histocompatibility complex I. This
      study provides the first molecular profile of human ltNSCctx cultures capable of
      long-term self renewal, and reveals specific sets of genes that are directly or
      indirectly regulated by LIF.

PMID- 12807439
TI  - Alpha-synuclein protects naive but not dbcAMP-treated dopaminergic cell types
      from 1-methyl-4-phenylpyridinium toxicity.
AB  - The pre-synaptic protein, alpha-synuclein, has been associated with the
      pathogenesis of Parkinson's disease. The present study indicates that alpha
      synuclein, but not its mutants (A53T, A30P), can protect CNS dopaminergic cells
      from the parkinsonism-inducing drug 1-methyl-4-phenylpyridinium (MPP+), whereas
      it cannot protect from the dopaminergic toxin, 6-hydroxydopamine, hydrogen
      peroxide, or the beta-amyloid peptide, A-beta. Protection from MPP+ was directly
      correlated with the preservation of mitochondrial function. Specifically, alpha
      synuclein rescued cells from MPP+ mediated decreases in mitochondrial
      dehydrogenase activity and loss of ATP levels by utilizing ketosis. It also
      prevented toxin-induced activation of the creatine kinase/creatine phosphate
      system. Similarly, alpha-synuclein protected cells from the complex I inhibitor
      rotenone and 3-nitroproprionic acid, a complex II inhibitor. Wild-type alpha
      synuclein-mediated neuroprotection and subsequent alterations in energy were not
      found in dbcAMP-differentiated cells. These results suggest that the normal
      physiological role for alpha-synuclein may change during development.

PMID- 12807440
TI  - Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout
      mice.
AB  - Clearance rates for serotonin (5-HT) in heterozygote (+/-) and homozygote (-/-)
      serotonin transporter (5-HTT) knockout (KO) mice have not been determined in
      vivo. Moreover, the effect of selective serotonin reuptake inhibitors (SSRIs) on
      5-HT clearance in these mice has not been examined. In this study, the rate of
      clearance of exogenously applied 5-HT was measured in the CA3 region of the
      hippocampus of anesthetized mice using high-speed chronoamperometry. Compared
      with wild-type mice, the maximal rate of 5-HT clearance from extracellular fluid
      (ECF) was decreased in heterozygotes and more markedly so in KO mice.
      Heterozygote mice were more sensitive to the 5-HT uptake inhibitor, fluvoxamine,
      resulting in longer clearance times for 5-HT than in wild-type mice; as expected,
      the KO mice were completely unresponsive to fluvoxamine. There were no associated
      changes in norepinephrine transporter density, nor was there an effect of the
      norepinephrine uptake inhibitor, desipramine, on 5-HT clearance in any genotype.
      Thus, adaptive changes in the norepinephrine transport system do not occur in the
      CA3 region of hippocampus as a consequence of 5-HTT KO. These data highlight the
      potential of the heterozygote 5-HTT mutant mice to model the dynamic in vivo
      consequences of the human 5-HTT polymorphism.

PMID- 12807441
TI  - The influence of brain inflammation upon neuronal adenosine A2B receptors.
AB  - Alzheimer's disease (AD) is associated with glial activation and increased levels
      of pro-inflammatory cytokines. Epidemiological results suggest that anti
      inflammatory therapies can slow the onset of AD. Adenosine, acting at type-2
      receptors, is an effective endogenous anti-inflammatory agent that can modulate
      inflammation both in the periphery and the brain. We investigated changes in the
      expression of adenosine type-2B (A2B) receptors and a related intracellular
      second messenger during chronic brain inflammation and following treatment with
      the non-steroidal anti-inflammatory drug flurbiprofen and its nitric oxide (NO)
      donating derivative, HCT1026. Chronic infusion of lipopolysaccharide (LPS) into
      the 4th ventricle of young rats induced brain inflammation that was associated
      with microglial activation and reduced neuronal immunoreactivity for adenosine
      A2B receptors in the cortex. Daily administration of HCT1026, but not
      flurbiprofen, reduced microglial activation, prevented the down-regulation of A2B
      receptors and elevated tissue levels of cAMP. The results suggest that a therapy
      using an NO-releasing NSAID might significantly attenuate the processes that
      drive the pathology associated with AD and that this process may involve the
      activation of adenosine A2B receptors.

PMID- 12807442
TI  - Differential effect of nitric oxide on glutathione metabolism and mitochondrial
      function in astrocytes and neurones: implications for
      neuroprotection/neurodegeneration?
AB  - Primary culture rat astrocytes exposed to the long acting nitric oxide donor (Z)
      1-[2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) for
      24 h approximately double their concentration of glutathione (GSH) and show no
      sign of cell death. In contrast, GSH was depleted by 48%, and significant loss of
      mitochondrial respiratory chain complex activity and cell death were observed in
      primary culture rat neurones subjected to DETA-NO for 18 h. Northern blot
      analysis suggested that mRNA amounts of both subunits of glutamate-cysteine
      ligase (GCL), the rate-limiting enzyme in GSH synthesis, were elevated in
      astrocytes following nitric oxide (NO) exposure. This correlated with an increase
      in astrocytic GCL activity. Neurones on the other hand did not exhibit increased
      GCL activity when exposed to NO. In addition, the rate of GSH efflux was doubled
      and gamma-glutamyltranspeptidase (gamma-GT) activity was increased by 42% in
      astrocytes treated with NO for 24 h. These results suggest that astrocytes, but
      not neurones, up-regulate GSH synthesis as a defence mechanism against excess NO.
      It is possible that the increased rate of GSH release and activity of gamma-GT in
      astrocytes may have important implications for neuroprotection in vivo by
      optimizing the supply of GSH precursors to neurones in close proximity.

PMID- 12807443
TI  - Increased activin levels in cerebrospinal fluid of rabbits with bacterial
      meningitis are associated with activation of microglia.
AB  - Activin, a member of the transforming growth factor superfamily, is upregulated
      in a number of inflammatory episodes such as septicemia and rheumatoid arthritis.
      In the CNS, activin has been predominantly assessed in terms of a neuroprotective
      role. In this report we characterized the activin response in the CNS in a rabbit
      model of meningitis. In normal animals, cerebrospinal fluid (CSF) activin levels
      were higher than those in serum, indicating an intracranial secretion of this
      cytokine. Following intracisternal inoculation with Streptococcus pneumoniae,
      activin in CSF was unchanged for the first 12 h and then rose progressively;
      levels were increased approximately 15-fold within 24 h. Activin levels were
      correlated positively with CSF protein content and with the number of apoptotic
      neurons in the dentate gyrus. No apparent correlation was observed between CSF
      activin concentrations and bacterial titer, lactate concentrations or leukocyte
      density. Using immunohistochemistry, activin staining was localized to epithelial
      cells of the choroid plexus, cortical neurons and the CA3 region of the
      hippocampus, with similar staining intensities in both normal and meningitic
      brains. However, in meningitic brains there was also strong staining in activated
      microglia and infiltrating macrophages. Taken together, these results demonstrate
      that activin forms part of the CNS response to immune challenge and may be an
      important mediator to modulate inflammatory processes in the brain.

PMID- 12807444
TI  - Secretion of interleukin-1beta by astrocytes mediates endothelin-1 and tumour
      necrosis factor-alpha effects on human brain microvascular endothelial cell
      permeability.
AB  - Evidence suggests that endothelin-1 (ET-1) plays an essential role in brain
      inflammation. However, whether ET-1 contributes directly to blood-brain barrier
      (BBB) breakdown remains to be elucidated. Using an in vitro BBB model consisting
      of co-cultures of human primary astrocytes and brain microvascular endothelial
      cells (BMVECs), we first investigated the expression of ET-1 by BMVECs upon
      stimulation with tumour necrosis factor (TNF)-alpha, which plays an essential
      role in the induction and synthesis of ET-1 during systemic inflammatory
      responses. Increased ET-1 mRNA was detected in the human BMVECs 24 h after TNF
      alpha treatment. This was correlated with an increase in ET-1 levels in the
      culture medium, as determined by sandwich immunoassay. Both TNF-alpha and ET-1
      increased the permeability of human BMVECs to a paracellular tracer, sucrose, but
      only in the presence of astrocytes. The increase in BMVEC permeability by TNF
      alpha was partially prevented by antibody neutralization of ET-1 and completely
      by monoclonal antibody against IL-1beta. Concomitantly, TNF-alpha induced IL
      1beta mRNA expression by astrocytes in co-culture and this effect was partially
      prevented by ET-1 antibody neutralization. In parallel experiments, treatment of
      human primary astrocytes in single cultures with ET-1 for 24 h induced IL-1beta
      mRNA synthesis and IL-1beta protein secretion in the cell culture supernatant.
      Taken together, these results provide evidence for paracrine actions involving ET
      1, TNF-alpha and IL-1beta between human astrocytes and BMVECs, which may play a
      central role in BBB breakdown during CNS inflammation.

PMID- 12807445
TI  - Characterization of a novel G-protein coupled receptor from the parasitic
      nematode H. contortus with high affinity for serotonin.
AB  - The neurotransmitter serotonin (5HT) has been shown to modulate mobility,
      feeding, egg-laying, and defecation behaviors in the saprophytic nematode
      Caenorhabditis elegans. Although the effects of serotonin on these behaviors in
      parasitic nematodes is under study, little is known about the diversity,
      ontogeny, signaling, and pharmacology of serotonin receptors in these organisms.
      In an effort to increase our understanding of this system, we cloned and
      characterized a novel cDNA (5HT1Hc) from the parasitic nematode Haemonchus
      contortus that has high amino acid sequence homology with known G-protein coupled
      5HT1-receptors from invertebrates and vertebrates. Transcript expression studies
      in four development stages (egg, L1/L2, L3, and adult) revealed the presence of
      the mRNA in the L1/L2, L3, and adult stages. Membranes from insect cells (Sf9)
      expressing the 5HT1Hc-receptor cDNA displayed nanomolar binding affinity to
      serotonin and a unique pharmacological profile distinct from known invertebrate
      and mammalian 5HT-receptors. Receptor signaling studies with mammalian AV12 cells
      expressing the 5HT1Hc-receptor and the promiscuous G-protein, Galpha15,
      demonstrated dose-dependent intracellular signals with serotonin acting as an
      agonist. Together, these studies describe a novel invertebrate 5HT-receptor with
      high affinity for the indolealkylamine, serotonin, and pharmacological properties
      that do not conform to any known members of this superfamily of metabotropic
      receptors.

PMID- 12807446
TI  - Increased survival and neuroprotective effects of BN82451 in a transgenic mouse
      model of Huntington's disease.
AB  - There is substantial evidence that excitotoxicity and oxidative damage may
      contribute to Huntington's disease (HD) pathogenesis. We examined whether the
      novel anti-oxidant compound BN82451 exerts neuroprotective effects in the R6/2
      transgenic mouse model of HD. Oral administration of BN82451 significantly
      improved motor performance and improved survival by 15%. Oral administration of
      BN82451 significantly reduced gross brain atrophy, neuronal atrophy and the
      number of neuronal intranuclear inclusions at 90 days of age. These findings
      provide evidence that novel anti-oxidants such as BN82451 may be useful for
      treating HD.

PMID- 12807448
TI  - Growth-inhibiting effects of seco-tanapartholides identified in Artemisia
      princeps var. orientalis whole plant on human intestinal bacteria.
AB  - AIMS: The present work aimed at isolating antibacterial constituents from the
      whole plant of Artemisia princeps var. orientalis active towards nine human
      intestinal bacteria. METHODS AND RESULTS: The growth-inhibiting activities of
      materials derived from the Artemisia whole plant towards test bacteria were
      examined using an impregnated paper disc method. The biologically active
      constituents of the Artemisia whole plant were characterized as the sesquiterpene
      lactones seco-tanapartholides A and B by spectroscopic analysis. In a test using
      1 mg per disc, seco-tanapartholides A and B produced a clear inhibitory effect
      against Clostridium perfringens, Bacteroides fragilis and Staphylococcus aureus.
      These compounds did not affect the growth of test lactic acid-producing bacteria
      (Bifidobacterium adolescentis, Bif. breve, Lactobacillus acidophilus and Lact.
      casei) and Escherichia coli, whereas weak growth inhibition towards Bif. bifidum
      was observed. At 0.5 mg per disc, seco-tanapartholides A and B exhibited moderate
      growth inhibition towards Cl. perfringens but weak growth inhibition towards
      Bact. fragilis and Staph. aureus. CONCLUSIONS: Inhibitory action of seco
      tanapartholides A and B towards specific bacteria without any adverse effects on
      lactic acid-producing bacteria may be an indication of at least one of the
      pharmacological actions of A. princeps var. orientalis whole plant. SIGNIFICANCE
      AND IMPACT OF THE STUDY: These naturally occurring Artemisia whole plant-derived
      materials could be useful as a new preventive agent against various diseases
      caused by harmful intestinal bacteria such as clostridia.

PMID- 12807449
TI  - Molecular detection of Candida krusei contamination in fruit juice using the
      citrate synthase gene cs1 and a potential role for this gene in the adaptive
      response to acetic acid.
AB  - AIMS: To develop a reverse transcription-polymerase chain reaction (RT-PCR) assay
      to detect viable Candida krusei contaminations and examine the potential role of
      the citrate synthase (cs1) gene in adaptation to acetic acid. METHODS AND
      RESULTS: Fruit juice artificially contaminated with C. krusei cells was heat
      treated to inactivate the yeast cells, after which the improved ability of the RT
      PCR over the PCR assay, through the amplification of the cs1 gene, to
      differentiate viable contaminations was shown. The sensitivity of the detection
      assay was 6 x 104 CFU ml-1. RT-PCR and densitometric analysis of the cs1 gene
      throughout the process of adaptation to acetic acid highlighted a potential role
      for the gene in the yeast's adaptive response. CONCLUSIONS: The RT-PCR assay
      through the targeting of the cs1 gene proved to be a specific, sensitive and
      direct method for the identification of a C. krusei contamination in a food
      environment. The cs1 gene was shown to play a potential role in the adaptation of
      the culture to the weak-acid preservative acetic acid. SIGNIFICANCE AND
      IMPORTANCE OF THE STUDY: The development of a direct, sensitive and specific
      identification assay for C. krusei from a food environment and understanding the
      mechanism employed in adapting to a preservative challenge, represent important
      tools to the food industry in attempting to limit spoilage by this important food
      spoilage yeast.

PMID- 12807450
TI  - Cloning and study of the expression of a novel cry1Ia-type gene from Bacillus
      thuringiensis subsp. kurstaki.
AB  - AIMS: Cloning and expression of a new cry1Ia-type gene of Bacillus thuringiensis.
      METHODS AND RESULTS: PCR amplification, using gene cry1I-specific primers
      revealed the presence of such a gene in the strain BNS3 of Bacillus thuringiensis
      subsp. kurstaki. The cloning and sequencing from BNS3 of the cry1Ia-type gene,
      called crybns3-3, showed an open reading frame of 2160-bp, encoding a protein of
      719 amino acid residues. Both nucleotide and amino acid sequences similarity
      analysis revealed that the crybns3-3 is a new cry1Ia-type gene, presenting
      several differences from the cry1Ia-type genes. The study of the expression of
      crybns3-3 by Northern blot and RT-PCR showed that it was transcribed. The
      expression of crybns3-3 under the control of BtI and BtII promoters revealed that
      Crybns3-3 would co-crystallize with the endogenous delta-endotoxins. CONCLUSIONS:
      crybns3-3 is a novel cry1Ia gene isolated from B. thuringiensis subsp. kurstaki
      strain BNS3. SIGNIFICANCE AND IMPACT OF THE STUDY: The characteristics of crybns3
      3 indicate that it is a new cry1Ia-type gene. Amino acid residue substitutions
      presented in Crybns3-3 could be exploited for both toxicity and specificity
      studies. Crybns3-3 would interact and co-crystallize at least partially with the
      endogenous delta-endotoxins of BNS3, and then participate in the formation of the
      parasporal crystal inclusions.

PMID- 12807451
TI  - Usefulness of different groups of bacteriophages as model micro-organisms for
      evaluating chlorination.
AB  - AIMS: To assess the usefulness of bacterial and viral indicators in chlorination
      processes and to collect quantitative information necessary for risk assessment
      analysis in water disinfection processes based on chlorination. METHODS AND
      RESULTS: Naturally occurring bacterial indicators, bacteriophages and
      enteroviruses were determined to evaluate the effect of chlorination in
      groundwater and secondary sewage effluents. Additionally, the effect of
      chlorinating on selected bacteriophages, enteroviruses and Escherichia coli was
      also tested in spiked samples of bottled water and sewage effluents. Results
      indicate that chlorination inactivates more efficiently bacteria than phages and
      enteroviruses. Among the human viruses, phages infecting Bacteroides fragilis and
      selected somatic coliphages belonging to the Siphoviridae family were the most
      persistent to chlorination. CONCLUSIONS: The three groups of bacteriophages
      studied were all more resistant to chlorination than bacteria and some of the
      phages were more resistant than enteroviruses. Results presented here indicate
      that it is very risky to generalize from information obtained with inactivation
      experiments done with single isolates of any phage or virus. If possible,
      inactivation studies should be done with naturally occurring populations. Phages
      offer a good opportunity for studying naturally occurring populations. Thus, the
      bacteriophages offer a range of resistance to chlorination that may represent
      most of the viruses that can be found in water. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Data reported in this study support the inclusion of bacteriophages as
      additional indicators of the efficiency of water chlorination processes and water
      quality.

PMID- 12807452
TI  - Identification of a new putative enterotoxin SEU encoded by the egc cluster of
      Staphylococcus aureus.
AB  - AIMS: This paper reports on a new putative enterotoxin SEU encoded by the
      enterotoxin gene cluster egc from Staphylococcus aureus and on a real-time
      polymerase chain reaction (PCR) assay for detecting the seu gene. METHODS AND
      RESULTS: PCR and sequencing revealed a new putative enterotoxin SEU encoded by
      some egc clusters. The seu gene resulted from sequence divergence in the psient1
      and psient2 pseudogenes previously described in the egc cluster (Jarraud et al.
      [2001] Journal of Immunology166, 669). The presence of the seu gene was
      investigated in a collection of S. aureus strains by conventional PCR and by a
      specific 5'-nuclease PCR assay. Among the 24 strains harbouring the egc cluster,
      four tested positive for the seu gene. CONCLUSIONS: The existence of the seu gene
      adds to the number of newly described se genes and underlines the need for a
      better understanding of their role in the pathogenesis of S. aureus. SIGNIFICANCE
      AND IMPACT OF THE STUDY: A thorough study of the seu gene should provide further
      insight into the phylogenetics of the staphylococcal enterotoxins.

PMID- 12807453
TI  - A two-stage continuous culture system to study the effect of supplemental alpha
      lactalbumin and glycomacropeptide on mixed cultures of human gut bacteria
      challenged with enteropathogenic Escherichia coli and Salmonella serotype
      Typhimurium.
AB  - AIMS: Certain milk factors may promote the growth of a gastrointestinal
      microflora predominated by bifidobacteria and may aid in overcoming enteric
      infections. This may explain why breast-fed infants experience fewer intestinal
      infections than their formula-fed counterparts. The effect of formula
      supplementation with two such factors was investigated in this study. METHODS AND
      RESULTS: Infant faecal specimens were used to ferment formulae supplemented with
      glycomacropeptide (GMP) and alpha-lactalbumin (alpha-la) in a two-stage compound
      continuous culture model. At steady state, all fermenter vessels were inoculated
      with 5 ml of 0.1 m phosphate-buffered saline (pH 7.2) containing 108 CFU ml-1 of
      either enteropathogenic Escherichia coli 2348/69 (O127:H6) or Salmonella serotype
      Typhimurium (DSMZ 5569). Bacteriology was determined by independent fluorescence
      in situ hybridization. Vessels that contained breast milk (BM), as well as alpha
      la and GMP supplemented formula had stable total counts of bifidobacteria while
      lactobacilli increased significantly only in vessels with breast milk.
      Bacteroides, clostridia and E. coli decreased significantly in all three groups
      prior to pathogen addition. Escherichia coli counts decreased in vessels
      containing BM and alpha-la while Salmonella decreased significantly in all
      vessels containing BM, alpha-la and GMP. Acetate was the predominant acid.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Supplementation of infant formulae with
      appropriate milk proteins may be useful in mimicking the beneficial
      bacteriological effects of breast milk.

PMID- 12807454
TI  - Mechanisms of killing of Bacillus subtilis spores by hypochlorite and chlorine
      dioxide.
AB  - AIMS: To determine the mechanisms of Bacillus subtilis spore killing by
      hypochlorite and chlorine dioxide, and its resistance against them. METHODS AND
      RESULTS: Spores of B. subtilis treated with hypochlorite or chlorine dioxide did
      not accumulate damage to their DNA, as spores with or without the two major DNA
      protective alpha/beta-type small, acid soluble spore proteins exhibited similar
      sensitivity to these chemicals; these agents also did not cause spore mutagenesis
      and their efficacy in spore killing was not increased by the absence of a major
      DNA repair pathway. Spore killing by these two chemicals was greatly increased if
      spores were first chemically decoated or if spores carried a mutation in a gene
      encoding a protein essential for assembly of many spore coat proteins. Spores
      prepared at a higher temperature were also much more resistant to these agents.
      Neither hypochlorite nor chlorine dioxide treatment caused release of the spore
      core's large depot of dipicolinic acid (DPA), but hypochlorite- and chlorine
      dioxide-treated spores much more readily released DPA upon a subsequent normally
      sub-lethal heat treatment than did untreated spores. Hypochlorite-killed spores
      could not initiate the germination process with either nutrients or a 1 : 1
      chelate of Ca2+-DPA, and these spores could not be recovered by lysozyme
      treatment. Chlorine dioxide-treated spores also did not germinate with Ca2+-DPA
      and could not be recovered by lysozyme treatment, but did germinate with
      nutrients. However, while germinated chlorine dioxide-killed spores released DPA
      and degraded their peptidoglycan cortex, they did not initiate metabolism and
      many of these germinated spores were dead as determined by a viability stain that
      discriminates live cells from dead ones on the basis of their permeability
      properties. CONCLUSIONS: Hypochlorite and chlorine dioxide do not kill B.
      subtilis spores by DNA damage, and a major factor in spore resistance to these
      agents appears to be the spore coat. Spore killing by hypochlorite appears to
      render spores defective in germination, possibly because of severe damage to the
      spore's inner membrane. While chlorine dioxide-killed spores can undergo the
      initial steps in spore germination, these germinated spores can go no further in
      this process probably because of some type of membrane damage. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These results provide information on the mechanisms of the
      killing of bacterial spores by hypochlorite and chlorine dioxide.

PMID- 12807455
TI  - Protease, peptidase and esterase activities by lactobacilli and yeast isolates
      from Feta cheese brine.
AB  - AIMS: The study of peptidase, esterase and caseinolytic activity of Lactobacillus
      paracasei subsp. paracasei, Debaryomyces hansenii and Sacchromyces cerevisiae
      isolates from Feta cheese brine. METHODS AND RESULTS: Cell-free extracts from
      four strains of Lact. paracasei subsp. paracasei, four strains of D. hansenii and
      three strains of S. cerevisiae, isolated from Feta cheese brine were tested for
      their proteolytic and esterase enzyme activities. Lactobacillus paracasei subsp.
      paracasei strains had intracellular aminopeptidase, dipeptidyl aminopeptidase,
      dipeptidase, endopeptidase and carboxypeptidase activities. Esterases were
      detected in three of four strains of lactobacilli and their activities were
      smaller with higher molecular weight fatty acids. The strains of yeasts did not
      exhibit endopeptidase as well as dipeptidase activities except on Pro-Leu. Their
      intracellular proteolytic activity was higher than that of lactobacilli.
      Esterases from yeasts preferentially degraded short chain fatty acids.
      Lactobacilli degraded preferentially beta-casein. Caseinolytic activity of yeasts
      was higher than that of lactobacilli. CONCLUSIONS: The results suggest that Lact.
      paracasei subsp. paracasei and yeasts may contribute to the development of
      flavour in Feta cheese. SIGNIFICANCE AND IMPACT OF THE STUDY: Selected strains
      could be used as adjunct starters to make high quality Feta cheese.

PMID- 12807456
TI  - Fungi are the predominant micro-organisms responsible for degradation of soil
      buried polyester polyurethane over a range of soil water holding capacities.
AB  - AIMS: To investigate the relationship between soil water holding capacity (WHC)
      and biodegradation of polyester polyurethane (PU) and to quantify and identify
      the predominant degrading micro-organisms in the biofilms on plastic buried in
      soil. METHODS AND RESULTS: High numbers of both fungi and bacteria were recovered
      from biofilms on soil-buried dumb-bell-shaped pieces of polyester PU after 44
      days at 15-100% WHC. The tensile strength of the polyester PU was reduced by up
      to 60% over 20-80% soil WHC, but no reduction occurred at 15, 90 or 100% soil
      WHC. A PU agar clearance assay indicated that fungi, but not bacteria were, the
      major degrading organisms in the biofilms on polyester PU and 10-30% of all the
      isolated fungi were able to degrade polyester PU in this assay. A 5.8S rDNA
      sequencing identified 13 strains of fungi representing the three major colony
      morphology types responsible for PU degradation. Sequence homology matches
      identified these strains as Nectria gliocladioides (five strains), Penicillium
      ochrochloron (one strain) and Geomyces pannorum (seven strains). Geomyces
      pannorum was the predominant organism in the biofilms comprising 22-100% of the
      viable polyester PU degrading fungi. CONCLUSIONS: Polyester PU degradation was
      optimum under a wide range of soil WHC and the predominant degrading organisms
      were fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: By identifying the predominant
      degrading fungi in soil and studying the optimum WHC conditions for degradation
      of PU it allows us to better understand how plastics are broken down in the
      environment such as in landfill sites.

PMID- 12807457
TI  - Bile salts and cholesterol induce changes in the lipid cell membrane of
      Lactobacillus reuteri.
AB  - AIMS: The objective of this study was to evaluate the effect of bile salts and
      cholesterol in the lipid profile of Lactobacillus reuteri CRL 1098 and to
      determine the relationship existing between these changes: the in vitro removal
      of cholesterol and the tolerance of the cells to acid and cold stress. METHODS
      AND RESULTS: Lactobacillus reuteri CRL 1098 was grown in the following media: MRS
      (deMan Rogosa Sharpe; MC, control medium), MB (MC with bile salts), MCH (MC with
      sterile cholesterol) and MBCH (MC with bile salts and cholesterol). Fatty acids
      were determined by analytical gas-liquid chromatography, and phospholipids and
      glycolipids by colorimetric techniques. The cells from different culture media
      were subjected to cold and acid stress. The MB cultures displayed a decrease in
      phospholipids and a low ratio of saturated : unsaturated fatty acids. The
      presence of the unusual C18 : 0,10-OH and C18 : 0,10-oxo fatty acids was the
      prominent characteristic of the bile salts growing cells. The relative increase
      in glycolipids and the changes in the fatty acids profiles of the MB cells would
      be responsible for the cholesterol remotion. The changes induced by bile salts in
      the lipid profile did not improve the tolerance of L. reuteri CRL 1098 to
      freezing and acid stress. CONCLUSIONS: The changes in lipid profiles reported in
      this study would play a key role in the response of Lactobacilli to environmental
      stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides useful
      information about the effect of bile salts on the cell membrane of L. reuteri, a
      probiotic enterolactobacillus. The steady-state response of the cells subjected
      to bile stress seems to be the appropriate model for evaluating the bacterial
      behaviour in detergent-containing gastrointestinal tracts, where the bile salts
      stress would presumably be continuous.

PMID- 12807458
TI  - Animal host associated differences in Shiga toxin-producing Escherichia coli
      isolated from sheep and cattle on the same farm.
AB  - AIMS: To investigate if cattle on the same farm as sheep are a possible risk
      factor for stx in sheep and to determine whether or not sheep and cattle on the
      same farm share the same stx pool. METHODS AND RESULTS: Faecal samples from sheep
      and cattle were screened for stx by polymerase chain reaction (PCR). Of these
      samples, 87.6 and 64.6% were stx positive in sheep and cattle, respectively.
      There was no difference in stx occurrence in sheep from farms with or without
      cattle. From stx positive samples, 118 Shiga toxin-producing Escherichia coli
      (STEC) isolates were recovered by a filter-hybridization method. Serotyping, PCR
      and pulsed-field gel electrophoresis (PFGE) showed that there was a distinct
      association between serotypes, stx profiles and animal species. CONCLUSIONS:
      Keeping animals together in pens, which enhances faecal-oral contact, is
      suggested as a possible explanation for the differences seen in stx occurrence.
      Sheep and cattle isolates are distinctly different in serotype and stx profile
      although isolated from the same farm, and are more related to isolates within the
      same serotype with the same stx profile than to isolates with different serotype
      from the same farm. SIGNIFICANCE AND IMPACT OF STUDY: The study supports the
      animal-host relationship hypothesis suggested in other studies and indicates that
      the STEC sheep reservoir in Norway may not pose a serious public health risk.

PMID- 12807459
TI  - Genetic transfer of the mcd gene in soil.
AB  - AIMS: To investigate the role of horizontal gene transfer of mcd (methylcarbamate
      degrading) gene in high genetic diversity of carbofuran-degrading bacteria.
      METHODS AND RESULTS: The actuality of genetic transfer from degraders to an
      Agrobacterium tumefaciens strain was determined in liquid medium. The mcd gene
      was chosen for transfer experiments. Transconjugants were obtained irrespective
      of the type of the donor strain (Gram-positive or Gram-negative), size of the
      inoculum, or nature and concentration of the pesticide in the medium. Soil
      microcosms, inoculated with or without the donor and/or recipient strains were
      used. The size of the initial degrading population (treated or untreated soil)
      and the nature of the inoculated donor strains were considered. More
      transconjugants were isolated in the previously treated soil than in the
      untreated soil. Agrobacterium transconjugants were isolated even when the donor
      strain was not inoculated, probably as a result of gene transfer from indigenous
      degrading population to the recipient strain. Moreover, potential transconjugants
      belonging to the Pseudomonas genus were isolated. CONCLUSIONS: Our results seem
      to demonstrate that the mcd gene is transferable in soil among bacterial
      populations. SIGNIFICANCE AND IMPACTS OF THE STUDY: The transfer of the mcd gene
      is partly responsible for the high genetic diversity of micro-organisms able to
      catabolize carbofuran.

PMID- 12807460
TI  - Comparison of microbial communities in four different composting processes as
      evaluated by denaturing gradient gel electrophoresis analysis.
AB  - AIMS: We aimed to systematically understand the composting processes by a
      comparison of microbial communities during four full-scale composting processes.
      METHODS AND RESULTS: Microbial communities during the four different full-scale
      composting processes were analysed by denaturing gradient gel electrophoresis
      combined with measurement of physicochemical parameters. Two composting processes
      utilized sewage sludge and two utilized food-waste. Comparison of the four
      processes indicated that the concentration of dissolved organic carbon was higher
      in the food-waste-composting than in the sewage-sludge-composting processes, and
      microbial communities varied with composting substrate. The tendency for
      different microbes to appear in the composting process with different
      concentrations of dissolved organic carbon agreed with a previous study that
      showed that microbial succession occurred with a decrease in dissolved organic
      carbon in a laboratory-scale food-waste-composting process. CONCLUSIONS: Our
      results suggested that the main factor affecting microbial communities in the
      composting process is the concentration of dissolved organic materials.
      SIGNIFICANCE AND IMPACT OF THE STUDY: In addition to studying microbial
      communities involved in composting, this research is also the first to study
      composting mechanisms using molecular methods. The results of our studies may be
      helpful in the design and management of composting processes.

PMID- 12807461
TI  - Development of multicolour digital image analysis system to enumerate actively
      respiring bacteria in natural river water.
AB  - AIMS: To develop a rapid and simple method for the assessment of metabolic
      activity of bacteria in natural environment. METHODS AND RESULTS: A rapid and
      simple multicolour digital image analysis system for enumerating viable bacteria
      based on active fluorescent staining has been developed. This system can
      accurately differentiate actively respiring bacteria and non-respiring bacteria
      by distinctive colour information in the digital image captured by an
      epifluorescence microscope equipped with low magnification objective lens. An
      algorithm to distinguish bacteria from considerable detritus, which produced
      bright fluorescence in different colours, by colour segmentation has also been
      developed. This system was applied to river water samples, and the total and
      respiratory active bacterial counts by digital image analysis were highly related
      to those by epifluorescence microscopy (r2 = 0.96 and 0.93, respectively).
      CONCLUSION: This system allowed the rapid and simple differentiation of bacteria
      from detritus and concurrent assessment of their metabolic activity, with results
      being available within 1 h. SIGNIFICANCE AND IMPACT OF THE STUDY: The low
      magnification image analysis allows more rapid and simple quantification of
      bacteria and could considerably decrease image data amount and acquisition time.
      This system could be easily applied to the rapid analysis of microbes in various
      environments.

PMID- 12807462
TI  - Rapid sample preparation method for PCR-based detection of Escherichia coli
      O157:H7 in ground beef.
AB  - AIM: To develop an improved, rapid and sensitive sample preparation method for
      PCR-based detection of Escherichia coli O157:H7 in ground beef. METHODS AND
      RESULTS: Fresh ground beef samples were experimentally inoculated with varying
      concentrations of E. coli O157:H7. PCR inhibitors were removed and bacterial
      cells were concentrated by filtration and centrifugation, and lysed using
      enzymatic digestion and successive freeze/thaw cycles. DNA was purified and
      concentrated via phenol/chloroform extraction and the Shiga toxin 1 gene (stx1)
      was amplified using PCR to evaluate the sample preparation method. Without prior
      enrichment of cells in broth media, the detection limit was 103 CFU g-1 beef.
      When a 6 h enrichment step was incorporated, the detection limit was 1 CFU g-1
      beef. The total time required from beginning to end of the procedure was 12 h.
      CONCLUSIONS: The sample preparation method developed here enabled substantially
      improved sensitivity in the PCR-based detection of E. coli O157:H7 in ground
      beef, as compared to previous reports. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Superb sensitivity, coupled with quick turn-around time, relative ease of use and
      cost-effectiveness, makes this a useful method for detecting E. coli O157:H7 in
      ground beef.

PMID- 12807463
TI  - Modelling the combined effects of pH, temperature and sodium chloride stresses on
      the thermal inactivation of Bacillus subtilis spores in a buffer system.
AB  - AIMS: The inactivation of Bacillus subtilis 168 spores subjected to the combined
      stress of pH, temperature and sodium chloride in a buffer system was modelled.
      METHODS AND RESULTS: Bacillus subtilis 168 spore suspension in 50 mmol l-1
      potassium phosphate buffer was heated in an open system using a block heater. A
      second order polynomial equation was used to describe the relationship between
      pH, temperature, sodium chloride concentration and the logarithm of the decimal
      reduction time (D-value) of the spores. Response surface graphs were constructed
      to predict the inactivation within the experimental domain. The data obtained
      were also compared with those reported for B. subtilis in different media and
      foods included in a large reference-based database of thermal inactivation
      (ThermoKill Database, TKDB R9100), which was constructed in the laboratory.
      CONCLUSIONS: All the variables studied seemed to have a significant effect on the
      inactivation of B. subtilis 168 spores in potassium phosphate buffer. The
      coefficient of determination, r2, and an analysis of the residuals from the model
      indicated the adequacy of the model to predict the inactivation of B. subtilis
      spores within the range of the experimental variables studied. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The findings of this study will enable a better
      understanding of the inactivation of B. subtilis spores under the influence of
      the studied environmental variables. The model can be used by food industries to
      assess and monitor the shelf life of food products in the event of a chance
      contamination by B. subtilis spores.

PMID- 12807464
TI  - Reducing colonization of Salmonella Enteritidis in chicken by targeting outer
      membrane proteins.
AB  - AIMS: To evaluate the ability of Salmonella enterica ser. Enteritidis outer
      membrane proteins (OMPs) of 75.6 and 82.3 kDa to inhibit or reduce in vivo
      colonization of S. Enteritidis on intestinal mucosa in chickens. METHODS AND
      RESULTS: Nine-week-old specific-pathogen-free chickens were subcutaneously
      immunized with 75.6 or 82.3 kDa protein, and challenged with a virulent strain of
      S. Enteritidis. Chickens were killed, and portions of small intestine and caecum
      were removed at necropsy. The population of S. Enteritidis attached to chicken
      intestinal mucosa was determined. The population of S. Enteritidis recovered from
      the small intestine and caecum of chickens immunized with 75.6 or 82.3 kDa
      protein was significantly (P < 0.05) lower than that recovered from the control
      birds. CONCLUSIONS: Salmonella Enteritidis OMPs 75.6 kDa and 82.3 kDa were
      effective in reducing colonization of S. Enteritidis on intestinal mucosa in
      chickens. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella Enteritidis OMPs 75.6
      or 82.3 kDa could be used as potential vaccines to reduce S. Enteritidis
      colonization in chickens.

PMID- 12807465
TI  - Employment of stressful conditions during culture production to enhance
      subsequent cold- and acid-tolerance of bifidobacteria.
AB  - AIMS: This study examined whether exposure of early stationary phase
      Bifidobacterium longum and B. lactis cells to various combinations of reduced
      temperature, reduced pH and starvation would enhance the cells' subsequent cold-
      and/or acid-tolerance. METHODS AND RESULTS: Survival of B. longum in growth
      medium at 6 degrees C significantly (P < 0.05) increased as a result of starving
      cells for 30 or 60 min without any simultaneous decrease in temperature or pH.
      Acid-tolerance of B. lactis (at pH 3.5 in synthetic gastric fluid) increased
      significantly when the growth medium pH was decreased from 6.0 to 5.2 and cells
      experienced 30 or 60 min of starvation. Enhanced B. lactis acid-tolerance
      persisted through 8-11 weeks of -80 degrees C storage in the pH 5.2 growth
      medium. Upon addition to milk during yogurt manufacture, these cells initially
      had enhanced acid-tolerance relative to untreated cells but untreated cells
      became equally acid-tolerant during the first 2.5 h of yogurt manufacture.
      CONCLUSIONS: The cold- and acid-tolerance of bifidobacteria vary widely, but may
      be significantly increased by application of sub-lethal stress to early
      stationary phase cells during culture production. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The enhancement of B. lactis acid-tolerance observed in this study may be
      of potential importance in the production of effective ready-to-consume probiotic
      dietary supplements.

PMID- 12807467
TI  - Development of a Gram-negative selective agar (GNSA) for the detection of Gram
      negative microflora in sputa in patients with cystic fibrosis.
AB  - AIMS: To develop a selective agar medium to help detect and quantify Gram
      negative flora in the sputum of patients with cystic fibrosis (CF). METHODS AND
      RESULTS: A novel Gram-negative Selective Agar (GNSA) medium was developed
      consisting of tryptone soya broth (30 g), bacteriological agar no.1 (10 g), yeast
      extract (5 g), crystal violet (2 mg), nisin (48 mg), novobiocin (5 mg),
      cycloheximide (100 mg), amphotericin (2 mg) and double distilled water (1 l), for
      the selective culture of all Gram-negative flora from the sputum of patients with
      CF. GNSA was able to support the proliferation of all 34 Gram-negative organisms
      examined, including 23 species most commonly associated with CF, but was unable
      to support the growth of the 12 Gram-positive or seven fungal organisms examined.
      Sensitivity studies demonstrated that the GNSA medium was able to detect not less
      than 1.50 x 102 CFU ml-1 sputum Pseudomonas aeruginosa, 2.38 x 102 CFU ml-1
      sputum Burkholderia cepacia genomovar IIIb and 6.70 x 103 CFU ml-1 sputum
      Stenotrophomonas maltophilia. A comparison of the microbial flora detected in the
      sputa of 12 adult CF patients by employment of routine bacteriological agar media
      and GNSA, demonstrated that GNSA was able to detect all Gram-negative organisms
      cultured by routine media, but had the advantage of detecting Alcaligenes
      xylosoxidans in two CF patients, whom had no previous history of Gram-negative
      infection. CONCLUSIONS: GNSA was unable to support the proliferation of any Gram
      positive organism or yeast/fungi, but was successful in supporting the growth of
      all Gram-negative organisms challenged. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Employment of this medium coupled with semi-automated technology may aid in
      helping to efficiently determine Gram-negative loading of respiratory secretions,
      particularly in response to antibiotic intervention.

PMID- 12807466
TI  - A comparison of two pre-enrichment media prior to immunomagnetic separation for
      the isolation of E. coli O157 from bovine faeces.
AB  - AIMS: To compare the sensitivity of two pre-enrichment broth media prior to
      immunomagnetic separation for the isolation of Escherichia coli O157 from cattle
      faeces. METHODS AND RESULTS: One-gram portions of 721 cattle faeces collected
      from 43 farms were pre-enriched in buffered peptone water containing vancomycin,
      cefixime and cefsulodin (BPW-VCC) and buffered peptone water without additives
      (BPW-WOA), respectively. A total of 137 samples were positive for E. coli O157:
      127 pre-enriched with BPW-WOA and 89 pre-enriched in BPW-VCC. Representative
      isolates were tested for phage type, verotoxin and eae (E. coli attaching and
      effacing) gene sequences, resulting in the recognition of eight different types.
      All the E. coli O157 types recognized were isolated by both methods except for
      three different strains, each of which were isolated only on a single occasion:
      two by BPW-WOA and another by BPW-VCC. CONCLUSIONS: The results clearly
      demonstrate, under the conditions of this study, that BPW without antibiotics was
      the superior pre-enrichment medium for the isolation of E. coli O157 from cattle
      faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of BPW-WOA in preference to
      BPW-VCC for the isolation of E. coli O157 from cattle faeces in future research
      and outbreak studies should lead to a higher number of positive isolates.

PMID- 12807468
TI  - Studies on the mechanism of the osmoresistance of spores of Bacillus subtilis.
AB  - AIMS: To determine the reason that spores of Bacillus species, in particular
      Bacillus subtilis, are able to form colonies with high efficiency on media with
      very high salt concentrations. METHODS AND RESULTS: Spores of various Bacillus
      species have a significantly higher plating efficiency on media with high salt
      concentration (termed osmoresistance) than do log or stationary phase cells. This
      spore osmoresistance is higher on richer media. Bacillus subtilis spores lacking
      various small, acid-soluble spore proteins (SASP) were generally significantly
      less osmoresistant than were wild-type spores, as shown previously (Ruzal et al.
      1994). Other results included: (a) spore osmoresistance varied significantly
      between species; (b) the osmoresistance of spores lacking SASP was not restored
      well by amino acid osmolytes added to plating media, but was completely restored
      by glucose; (c) the osmoresistance of spores lacking SASP was restored upon brief
      germination in the absence of salt in a process that did not require protein
      synthesis; (d) significant amounts of amino acids generated by SASP degradation
      were retained within spores upon germination in a medium with high but not low
      salt; (e) slowing but not abolishing SASP degradation by loss of the SASP
      specific germination protease (GPR) did not affect spore osmoresistance; (f)
      sporulation at higher temperatures produced less osmoresistant spores; and (g)
      spore osmoresistance was not decreased markedly by the absence of the stress
      sigma factor for RNA polymerase, sigmaB. CONCLUSIONS: Spore osmoresistance
      appears as a result of three major factors: (1) specific characteristics of
      spores and cells of individual species; (2) the precise sporulation conditions
      that produce the spores; and (3) sufficient energy generation by the germinating
      and outgrowing spore to allow the spore to adapt to conditions of high osmotic
      strength; the substrates for this energy generation can come from either the
      endogenous generation of amino acids by SASP degradation or from the spore's
      environment, in the form of a readily taken up and metabolized energy source such
      as glucose. SIGNFICANCE AND IMPACT OF STUDY: These results provide information on
      the mechanisms of spore osmoresistance, a spore property that can be of major
      applied significance given the use of high osmotic strength with or without high
      salt as a means of food preservation.

PMID- 12807469
TI  - Occurrence and antimicrobial resistance of Gram-negative bacteria isolated in
      haemodialysis water and dialysate of renal units: results of a Greek multicentre
      study.
AB  - AIMS: To evaluate the occurrence, identity and antimicrobial resistance of Gram
      negative bacteria isolated from municipal water supplies, treated water, and
      dialysate of all 85 Greek haemodialysis centres. METHODS AND RESULTS: A total of
      141 Gram-negative bacterial isolates (98 non-fermentative and 43 enterobacteria)
      were recovered from 255 water samples. Twenty-four of them were isolated from tap
      water, 31 from treated water, and 86 from dialysate samples. The mean
      concentrations (CFU per 100 ml +/- s.d.) of the positive Gram-negative bacteria
      samples were 69.2 +/- 43.9, 31.2 +/- 28.7 and 3552.3 +/- 4485.0, respectively.
      The most common isolates, in order of frequency were Pseudomonas aeruginosa
      (22.7%), Chryseobacterium meningosepticum (14.9%), Stenotrophomonas maltophilia
      (13.5%), Escherichia coli (12.8%) and Enterobacter cloacae (7.8%), representing
      71.6% of all isolates. Ps. aeruginosa was the most prevalent isolate in all types
      of water sample followed by C. meningosepticum in tap and treated water and by E.
      coli in dialysate. Nineteen per cent of the enterobacteria and 35% of the non
      fermenters were resistant against three or more of the nine antibiotics tested.
      CONCLUSIONS: These data suggest that dialysate and treated water could be a
      source of infection for several non-fermentative and enterobacterial species.
      IMPACT OF THE STUDY: Microbiological monitoring of such samples is needed in
      order to know the identity and antibiotic resistance profiles of their
      potentially pathogenic bacterial population.

PMID- 12807470
TI  - Characterization of Serratia marcescens surviving in disinfecting footbaths.
AB  - AIM: To determine if disinfecting footbaths in the food industry were
      contaminated with bacteria and to characterize some of the bacteria present.
      METHODS AND RESULTS: Bacterial strains were isolated from disinfecting footbaths
      containing TEGO 103G (amphoteric disinfectant) or TP-99 (alkyl amino acetate
      based disinfectant) in five of six dairy factories. Fourteen strains identified
      as Cedecea spp. by their fatty acid composition were further characterized.
      Results from Rapid ID 32 E API analysis and 16S-rDNA-sequencing showed that all
      strains were Serratia marcescens. Unlike S. marcescens ATCC 13880, the isolates
      from disinfecting footbaths were not killed (<5 log10 reduction) by the
      recommended in-use concentration of TEGO 103G, TEGO 51 or benzalkonium chloride.
      Survival and multiplication in tap water with an in-use concentration of TEGO
      103G was demonstrated for one of the strains. All strains were killed by the in
      use concentrations of commercial disinfectants based on peracetic acid,
      hypochlorite, quaternary ammonium compounds and alkyl amino acetate (TP-99).
      There were no indications of cross-resistance between disinfectants and
      antibiotics. CONCLUSION: Serratia marcescens may survive and multiply in
      disinfecting footbaths containing TEGO 103G or alkyl amino acetate because of
      disinfectant resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: Disinfecting
      footbaths may act as contamination sources in food factories and should not be
      used without regular hygienic monitoring.

PMID- 12807471
TI  - Comparative evaluation of the MGIT and BACTEC culture systems for the recovery of
      Mycobacterium avium subsp. paratuberculosis from milk.
AB  - AIMS: To compare the detection capabilities of the non-radiometric MGIT
      (Mycobacteria Growth Indicator Tubes) and radiometric BACTEC 460TB culture
      systems (Becton Dickinson, Cowley, Oxford, UK) for recovering Mycobacterium avium
      subsp. paratuberculosis from milk. METHODS AND RESULTS: Ultra heat treated (UHT)
      milk samples spiked with different levels of M. paratuberculosis (10-107 cells ml
      1) were inoculated into MGIT and BACTEC media (containing recommended
      supplements) with and without prior chemical decontamination of the milk samples
      with 0.75% (w/v) cetylpyridinium chloride for 5 h. Time for the detection of
      growth in days was recorded for each culture system, and a M. paratuberculosis
      count for each milk sample was calculated from BACTEC readings using a published
      formula. Correlation between MGIT and BACTEC detection times was 0.6983. Both
      culture systems were capable of detecting 10-100 M. paratuberculosis cells ml-1
      in milk within 30-40 days when no decontamination treatment was applied, but only
      102-103 cells ml-1 or greater when chemical decontamination was applied before
      culture. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF STUDY: The non-radiometric MGIT
      system could be substituted for the radiometric BACTEC system for the culture of
      M. paratuberculosis from milk without loss of detection sensitivity. Chemical
      decontamination before culture caused a significant reduction in numbers of
      viable M. paratuberculosis in all spiked milk samples resulting in decreased
      detection capability for both culture systems.

PMID- 12807475
TI  - A new infectious disease challenge: Urbani severe acute respiratory syndrome
      (SARS) associated coronavirus.

PMID- 12807474
TI  - The peripheral generation of CD4+ CD25+ regulatory T cells.

PMID- 12807476
TI  - Nicotine has suppressive effects on dendritic cell function.

PMID- 12807477
TI  - Limited role of charge matching in the interaction of human immunoglobulin A with
      the immunoglobulin A Fc receptor (Fc alpha RI) CD89.
AB  - Human immunoglobulin A (IgA) mediates protective effector mechanisms through
      interaction with specific cellular Fc receptors (Fc alpha RI). Two IgA Fc
      interdomain loops (Leu257-Leu258 in the CH2 domain and Pro440-Phe443 in the CH3
      domain) have previously been identified as critical for binding to Fc alpha RI.
      On the receptor, the interaction site for IgA has been localized to the EC1
      domain. The essential Fc alpha RI residues involved are Tyr35, Tyr81 and Arg82,
      with contributions also from Arg52 and to a lesser extent from His85 and Tyr86.
      The basic nature of the side chains of some of the receptor residues implicated
      in ligand binding suggested that charge matching might play some role in the
      interaction. To address this possibility, we have generated five IgA1 mutants
      with point substitutions in acidic residues lying close to the putative
      interaction site and assessed their abilities to bind Fc alpha RI on human
      neutrophils. Mutants E254A, E254L and E437A displayed affinities for Fc alpha RI
      comparable to that of wild-type IgA1, while mutants D255A and D255V had only
      slightly reduced affinities for the receptor. Therefore, electrostatic
      interactions appear unlikely to play a significant role in the IgA-Fc alpha RI
      interaction. Moreover, the lack of effect of mutations in residues adjacent to
      those previously implicated in binding, reaffirms the importance of the
      interdomain loops in Fc alpha RI binding.

PMID- 12807478
TI  - Differential T-cell activation by B7-1 expression.
AB  - T-cell receptor-mediated T-cell activation requires cosimulation signal, which
      can be provided by B7-1 molecule. Our previous study demonstrated that the
      coexpression of a covalent peptide/major histocompatibility complex class II
      molecule complex and costimulatory molecule B7-1 by recombinant adenovirus leads
      to synergy in peptide-specific T-cell activation. However, the viral antigen
      specific T-cell activation is not enhanced by B7-1 expressed by the adenovirus.
      To verify the differential T cell activation by B7-1 and investigate its
      underlying mechanisms, we constructed an adenovirus coexpressing a covalent
      complex of hen egg lysozyme peptide/I-Ak (HEL46-61/I-Ak) and B7-1 in the present
      study. In vivo studies revealed that HEL46-61-specific T-cell response, but not
      viral antigen-specific T-cell response, was enhanced by B7-1 expression mediated
      by the adenovirus, suggesting that exogenous B7-1 expression may regulate T-cell
      response to these two different antigens through distinct mechanisms.
      Furthermore, our results revealed that antigen-presenting cells were not
      susceptible to adenovirus infection in vivo. Based on these findings, the
      possible mechanism of differential B7-1 costimulation on peptide-specific and
      viral antigen-specific T-cell activation is discussed.

PMID- 12807479
TI  - Characterization of extrathymic CD8 alpha beta T cells in the liver and intestine
      in TAP-1 deficient mice.
AB  - TAP-1 deficient (-/-) mice cannot transport MHC class I antigens onto the cell
      surface, which results in failure of the generation of CD8+ T cells in the
      thymus. In a series of recent studies, it has been proposed that extrathymic T
      cells are generated in the liver and at other extrathymic sites (e.g. the
      intestine). It was therefore investigated whether CD8+ extrathymic T cells
      require an interaction with MHC class I antigens for their differentiation in TAP
      1(-/-) mice. Although CD8+ thymically derived T cells were confirmed to be absent
      in the spleen as well as in the thymus, CD8 alpha beta+ T cells were abundant in
      the livers and intestines of TAP-1(-/-) mice. These CD8+ T cells expanded in the
      liver as a function of age and were mainly confined to a NK1.1-CD3int population
      which is known to be truly of extrathymic origin. Hepatic lymphocytes, which
      contained CD8+ T cells and which were isolated from TAP-1(-/-) mice (H-2b),
      responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class
      I antigens (H-2d) in in vitro mixed lymphocyte cultures. However, the results
      from repeated in vivo stimulations with alloantigens (H-2d) were interesting.
      Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(-/-) mice,
      although the magnitude of cytotoxicity was lower than that of liver lymphocytes
      in immunized B6 mice. All allogeneic cytotoxicity disappeared with the
      elimination of CD8+ cells in TAP-1(-/-) mice. These results suggest that the
      generation and function of CD8+ extrathymic T cells are independent of the
      existence of the MHC class I antigens of the mouse but have a limited
      allorecognition ability.

PMID- 12807480
TI  - Appearance of the LAT protein at an early stage of B-cell development and its
      possible role.
AB  - The linker protein LAT is expressed mainly in T and natural killer (NK) cells.
      LAT-deficient mice have an arrest of intrathymic T-cell development at the CD4+
      CD8+ stage and lack mature T cells in the periphery. However, no gross
      abnormality in development and function of the B and NK cells has been described.
      Here we report that LAT is expressed in mouse progenitor B (pro-B) and precursor
      B (pre-B) cells, but not in immature or mature B cells. LAT in pre-B cells
      becomes tyrosine phosphorylated upon cross-linking of the pre-B-cell receptor
      (pre-BCR) by anti- micro antibody. Incubation of 1xN/2b (mouse pre-B-cell line)
      cells or bone marrow cells from microMT/ microMT mice, which lack B cells after
      the small pre-B-cell stage, with anti-Ig beta antibody resulted in the
      downregulation of LAT expression. Transgenic mice which expressed LAT protein in
      B-lineage cells showed an increased proportion of pro- and large pre-B cells in
      the bone marrow and a remarkable reduction in the numbers of mature B cells in
      peripheral lymphoid tissues. Collectively, the present results indicate that LAT
      is expressed in the cells at the early stages of B-lineage development, but is
      absent in immature and mature B cells. LAT may play a crucial role in the
      negative regulation of B-cell development at the transition from pre-B to mature
      B-cell stages, and signal(s) via the pre-BCR may extinguish LAT expression, thus
      allowing pre-B-cell differentiation towards the mature B-cell stage.

PMID- 12807481
TI  - Immature dendritic cells possess a sugar-sensitive receptor for human mannan
      binding lectin.
AB  - Mannan-binding lectin (MBL) is a collectin synthesized by the liver and secreted
      into the bloodstream. It has a receptor for microbial structures in its C-type
      lectin domain and a separate receptor(s) located within its collagen-like region
      for autologous phagocytic cells. Here we demonstrate that human peripheral blood
      adherent cells (monocytes) and monocyte-derived dendritic cells are a source of
      MBL, and that a novel calcium-dependent and sugar-specific MBL receptor is up
      regulated in immature (CD1a-positive) dendritic cells. These findings suggest a
      previously unsuspected autologous function for MBL, perhaps a regulatory role
      within the immune system.

PMID- 12807482
TI  - Evidence for the immunosuppressive role of nicotine on human dendritic cell
      functions.
AB  - Nicotine alters a wide range of immunological functions, including innate and
      adaptive immune responses. To date, no studies have been reported showing the
      immunoregulatory effects of nicotine on dendritic cells (DCs), which are critical
      cells for initiation of cell-mediated immunity against infection and neoplastic
      diseases. In this work, we report that, in a nicotinic environment, monocyte
      derived DCs manifest lower endocytic and phagocytic activities. Interestingly,
      although immature DCs undergo maturation in response to bacterial antigen
      lipopolysaccharide, they produce decreased levels of pro-inflammatory cytokines,
      notably interleukin-12, and reveal a reduced ability to stimulate antigen
      presenting cell-dependent T-cell responses. Importantly, the reduction in T-cell
      responses is associated with a diminished ability of DCs to induce
      differentiation and expansion of type 1 T cells, as evidenced by a decreased
      frequency of interferon-gamma-producing effector cells. These results strongly
      suggest that nicotine can exert its immunosuppressive effects on immune
      surveillance through functional impairment of the DC system.

PMID- 12807483
TI  - Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via
      a proteasome-independent mechanism of major histocompatibility complex class I
      loading.
AB  - Immune stimulating complexes (ISCOMS) containing the saponin adjuvant Quil A are
      vaccine adjuvants that induce a wide range of immune responses in vivo, including
      strong class I major histocompatibility complex (MHC)-restricted cytotoxic T
      lymphocyte activity. However, the antigen-presenting cell responsible for the
      induction of these responses has not been characterized. Here we have
      investigated the role of dendritic cells (DC) in the priming of antigen-specific
      CD8+ T cells in vitro by ISCOMS containing ovalbumin. Resting bone marrow DC
      pulsed with ovalbumin ISCOMS efficiently prime resting CD8+ T cells through a
      mechanism that is transporter associated with antigen processing (TAP) dependent,
      but independent of CD40 ligation and CD4+ T-cell help. Lipopolysaccharide-induced
      maturation of DC markedly enhances their ability to prime CD8+ T cells through a
      mechanism which is also independent of CD4+ T-cell help, but is dependent on CD40
      ligation. Furthermore, DC maturation revealed a TAP-independent mechanism of CD8+
      T-cell priming. Our results also show that class I MHC-restricted presentation of
      ovalbumin in ISCOMS by DC is sensitive to chloroquine and brefeldin A but
      insensitive to lactacystin. We suggest that DC may be the principal antigen
      presenting cells responsible for the priming of CD8+ T cells by ISCOMS in vivo
      and that targeting these vectors to activated DC may enhance their presentation
      via a novel pathway of class I antigen processing.

PMID- 12807484
TI  - Efficient antigen presentation of soluble, but not particulate, antigen in the
      absence of Wiskott-Aldrich syndrome protein.
AB  - B cells and dendritic cells, lacking functional Wiskott-Aldrich syndrome protein
      (WASP), have aberrant formation of membrane protrusions. We hypothesized that
      protrusions may play a role in antigen presentation, and consequently, that
      impaired antigen presentation may be an underlying factor of the immune
      deficiency in patients with Wiskott-Aldrich syndrome. In this paper, we
      investigated the antigen presentation capacity of B cells and dendritic cells
      from WASP knockout mice, using soluble and particulate antigen, to CD4+ T cells
      from T-cell receptor transgenic DO11.10 mice. As antigen we used soluble
      ovalbumin (OVA), a peptide thereof (amino acids 323-339) or bacteria expressing
      OVA. We found that WASP-deficient B cells and dendritic cells efficiently
      processed and presented soluble OVA protein as well as its peptide in vitro,
      inducing proliferation and cytokine production from CD4+ T cells. Antigen
      presentation of soluble protein was efficient also in vivo, because immunization
      of WASP-deficient mice with OVA elicited proliferation of transferred,
      fluorescent-labelled, CD4+ T cells. Although we could detect uptake of bacteria
      in dendritic cells, processing and presentation of bacterial-expressed OVA was
      impaired in WASP-deficient dendritic cells. In conclusion, our data suggest that
      WASP is not needed for processing and presentation of soluble antigen, but that
      efficient presentation of particulate antigen require WASP.

PMID- 12807485
TI  - Apolipoprotein E modulates immune activation by acting on the antigen-presenting
      cell.
AB  - Apolipoprotein E (ApoE) is synthesized by a variety of cells including
      macrophages. These cells activate T lymphocytes by antigen presentation, while
      the T-cell cytokine, interferon-gamma, inhibits macrophage ApoE expression. ApoE
      inhibits T-cell proliferation in culture but its role in immune responses has
      been unclear. The ApoE-deficient (E0) mouse permits an evaluation of the
      immunological role of ApoE. We have analysed T-cell responses to an exogenous
      antigen (ovalbumin) and polyclonal mitogen (concanavalin A) in E0 and ApoE+/+
      mice. Macrophages of E0 mice stimulated T-cell activation more effectively as
      antigen-presenting cells than macrophages from ApoE+/+ mice. Both proliferation
      and interferon-gamma secretion were enhanced in T cells activated in the context
      of antigen-presenting cells from E0 mice. Since the macrophage-T-cell interaction
      depends on interactions between cell surface molecules, we assessed the
      expression of such molecules after in vivo stimulation with interferon-gamma.
      This treatment caused an increased expression of the co-stimulatory surface
      proteins CD40 and CD80, and also of the major histocompatibility complex class II
      molecules I-Ab on macrophages of E0 mice compared with ApoE+/+. Our data suggest
      that ApoE inhibits T-cell activation by reducing the density of immune
      stimulatory proteins on antigen-presenting cells.

PMID- 12807486
TI  - Oestradiol regulation of antigen presentation by uterine stromal cells: role of
      transforming growth factor-beta production by epithelial cells in mediating
      antigen-presenting cell function.
AB  - We have previously shown that oestradiol treatment of ovariectomized rats for 3
      days inhibits antigen presentation by uterine stromal cells at a time when
      oestradiol increases the numbers of antigen-presenting cells (APC) in the uterine
      stroma. In the present study, we found that oestradiol treatment for 1 day is
      sufficient to inhibit antigen presentation by stromal cells. To define the
      mechanism(s) of this inhibition, we examined the effect of cytokines and found
      that exogenous transforming growth factor-beta (TGF-beta) inhibits antigen
      presentation when stromal cells from saline- but not oestradiol-treated animals
      are incubated with ovalbumin (OVA)-specific T cells and OVA. In contrast, antigen
      presentation by uterine epithelial cells was not affected by TGF-beta. In other
      studies, the acute inhibitory effect of oestradiol (1 day) on stromal antigen
      presentation is fully reversed when anti-TGF-beta antibody is added to the
      culture media. When given for 3 days, oestradiol inhibition of antigen
      presentation is partially reversed by anti-TGF-beta antibody at a time when
      antibodies to tumour necrosis factor-alpha and interleukin-10 have no effect. To
      determine whether uterine epithelial cells produce TGF-beta, epithelial cells
      were grown to confluence on transwell inserts. Our findings indicate that uterine
      epithelial cells produce biologically active TGF-beta which is preferentially
      released basolaterally in the direction of underlying stromal cells. When
      oestradiol is given to ovariectomized rats 1 day before sacrifice, TGF-beta
      production by epithelial cells increases within 24 hr in culture, relative to
      saline controls. Taken together, these results suggest that oestradiol inhibition
      of stromal cell antigen presentation is mediated through the stimulatory effect
      of oestradiol on TGF-beta production by epithelial cells.

PMID- 12807487
TI  - Induction of interleukin-12 production in mouse macrophages by berberine, a
      benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1
      response.
AB  - In this study we investigated whether berberine-mediated induction of interleukin
      12 (IL-12) production in antigen-presenting cells could regulate a cytokine
      profile of antigen-primed CD4+ T helper (Th) cells. Pretreatment with berberine
      induced IL-12 production in both macrophages and dendritic cells, and
      significantly increased the levels of IL-12 production in lipopolysaccharide
      stimulated macrophages and in CD40 ligand-stimulated dendritic cells.
      Importantly, berberine pretreatment of macrophages increased their ability to
      induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in
      antigen-primed CD4+ T cells. Berberine did not influence the macrophage cell
      surface expression of the class II major histocompatibility complex molecule, the
      co-stimulatory molecules CD80 and CD86, and intracellular adhesion molecule-1.
      Addition of neutralizing anti-IL-12p40 monoclonal antibody to cultures of
      berberine-pretreated macrophages and CD4+ T cells restored IL-4 production in
      antigen-primed CD4+ T cells. The in vivo administration of berberine resulted in
      the enhanced induction of IL-12 production by macrophages when stimulated in
      vitro with lipopolysaccharide or heat-killed Listeria monocytogenes, leading to
      the inhibition of the Th type 2 cytokine profile (decreased IL-4 and increased
      IFN-gamma production) in antigen-primed CD4+ T cells. These findings may point to
      a possible therapeutic use of berberine or medicinal plants containing berberine
      in the Th type 2 cell-mediated immune diseases such as allergic diseases.

PMID- 12807489
TI  - Effects of functional Toll-like receptor-4 mutations on the immune response to
      human and experimental sepsis.
AB  - Genetically determined responsiveness to microbial stimuli such as
      lipopolysaccharide (LPS) may affect the pathophysiology of human sepsis. The
      D299G mutation in human Toll-like receptor-4 (TLR4) impairs LPS signalling in
      homozygous and heterozygous individuals. To investigate whether the presence of
      the TLR4(D299G) mutation may correlate with the development or outcome of sepsis
      following major visceral surgery the presence of TLR4(D299G) mutation was
      analysed in 307 Caucasian patients (154 without and 153 with sepsis). Sepsis was
      caused in 84% of patients by polymicrobial infection. The presence of the mutant
      TLR4 did not significantly correlate with development or outcome of sepsis. Serum
      levels of tumour necrosis factor, interleukin (IL)-10, and IL-6 at sepsis onset
      did not significantly differ between patients carrying wild-type and mutant TLR4.
      Moreover, studies in a murine model of polymicrobial septic peritonitis
      demonstrated that TLR4-deficiency did neither influence the systemic cytokine
      response nor the development of organ injury. The results suggest that the
      signalling capacity of TLR4 as affected by loss-of-function mutations does not
      influence human or experimental sepsis caused by polymicrobial infection. Thus,
      in polymicrobial infection, other innate immune receptors may compensate for TLR4
      defects.

PMID- 12807488
TI  - Differential regulation of interleukin-12 p40 and p35 induction via Erk mitogen
      activated protein kinase-dependent and -independent mechanisms and the
      implications for bioactive IL-12 and IL-23 responses.
AB  - Bioactive interleukin (IL)-12 is a 70 000-molecular weight (MW) heterodimeric
      cytokine comprising p40 and p35 chains. However, p40 can also form homodimers
      that antagonize bioactive IL-12 or heterodimerize with p19 to form IL-23, which
      exhibits overlapping yet distinct functions to that of IL-12. We now define
      distinct signalling mechanisms that regulate lipopolysaccharide (LPS)-mediated
      induction of IL-12 p40 and p35 in macrophages and which may therefore provide
      therapeutic targets for precise and specific fine-tuning of cytokine responses.
      Thus, whilst LPS-induced p38 mitogen-activated protein kinase (MAPkinase)
      activation is required for the induction of both p40 and p35 subunits, Erk
      MAPkinase signalling mediates negative feedback regulation of p40, but not p35,
      production. Such Erk MAPkinase activation is downstream of calcium influx and
      targets LPS-induced IL-12 p40 transcription by suppressing the synthesis of the
      transcription factor, interferon regulatory factor-1 (IRF-1). In contrast,
      negative regulation of the p35 subunit of IL-12 occurs via a calcium-dependent,
      but Erk-independent, mechanism, which is likely to involve nuclear factor (NF)
      kappa B signalling. Finally, the importance of both Erk and p38 MAPkinases in
      differentially regulating IL-12 p40 and p35 production is underscored by each
      being targeted by ES-62, a product secreted by parasitic filarial nematodes to
      polarize the immune system towards an anti-inflammatory phenotype conducive to
      their survival.

PMID- 12807490
TI  - Protein kinase C is involved in 2B4 (CD244)-mediated cytotoxicity and AP-1
      activation in natural killer cells.
AB  - 2B4 (CD244) is a member of the CD2 subset of the immunoglobulin superfamily and
      functions as a triggering molecule on natural killer (NK) cells. Previously, we
      have found that 2B4-mediated activation of NK cells involves complex interactions
      involving LAT, Ras, Raf, ERK and p38 and that cytolytic function and cytokine
      production may be regulated by distinct pathways. Here we assessed the role of
      protein kinase C (PKC) in 2B4-mediated cytotoxicity of YT cells, a human NK cell
      line. Our data indicate that PKC-delta is activated upon stimulation with
      monoclonal antibody against 2B4. Treatment with the PKC inhibitor,
      bisindolylmaleimide I (Go6850), of YT cells or YT cells depleted of Ca2+
      dependent isoforms of PKC prior to 2B4 stimulation, resulted in inhibition of
      natural cytotoxicity and redirected antibody-dependent cellular cytotoxicity.
      However, inhibition of PKC failed to block 2B4 stimulation of interferon-gamma
      secretion as opposed to pretreatment with LY294002, a phosphoinositide 3-kinase
      inhibitor. We also examined the effect of phorbol 12-myristate 13-acetate (PMA)
      induction on 2B4 gene transcription. PMA induction resulted in a more than two
      fold increase of 2B4 transcription. However, when we introduced a three-base
      substitution mutation to disrupt the activator protein-1 binding site at (-106 to
      -100) in the 2B4 promoter, we found complete loss of transcriptional activity,
      including the two-fold increase due to PMA induction of PKC. The present study
      indicated that PKC may play an important role in 2B4 signalling and activator
      protein-1 activation.

PMID- 12807491
TI  - The role of interferon-gamma, nitric oxide and lipopolysaccharide in intestinal
      graft-versus-host disease developing in F1-hybrid mice.
AB  - (C57BL/6 x DBA/2)F1-hybrid mice injected with lymphoid cells from wild-type,
      C57BL/6 donors develop acute, lethal graft-versus-host disease (GVHD) in which
      the intestine is a major target. In its destructive phase intestinal GVHD is
      characterized by apoptosis of intestinal crypt epithelial cells and the
      development of endotoxaemia. Injection of as little as 10 microg endotoxin is
      lethal in mice with acute GVHD, and associated with the release of large amounts
      of tumour necrosis factor-alpha (TNF-alpha) into the serum. To explore the role
      of interferon-gamma (IFN-gamma) in the pathogenesis of intestinal GVHD we used
      IFN-gamma gene knockout (gko) mice as donors. Recipients of grafts from these
      donors did not develop intestinal GVHD and, unlike recipients of wild-type
      grafts, did not die when injected with lipopolysaccharide (LPS). We also found
      that injection 10 microg LPS into recipients of wild-type grafts induced
      apoptosis of intestinal epithelial crypt cells and was associated with a burst of
      nitric oxide production in the intestine. Administration of N(omega)nitro L
      arginine methyl ester blocked this response. In contrast, LPS did not induce
      either intestinal epithelial cell apoptosis or increased nitric oxide production
      in recipients of IFN-gamma gko grafts. These findings indicate that donor-derived
      IFN-gamma is instrumental for the development of intestinal GVHD. In a previous
      study we showed that recipients of IFN-gamma gko grafts develop high levels of
      LPS-induced TNF-alpha release. When our current data are viewed in the context of
      this observation, they suggest that intestinal epithelial cell apoptosis in the
      parent-->F1-hybrid model of acute GVHD is mediated primarily by nitric oxide
      rather than TNF-alpha, and that this depends on donor-derived IFN-gamma.

PMID- 12807493
TI  - Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic
      inflammation in sensitized rats.
AB  - Immunomodulators such as cyclosporin A (CsA) and SAR943 (32-deoxorapamycin)
      inhibit single allergen-induced allergic inflammation such as eosinophilic and
      lymphocytic infiltration and mRNA expression for interleukin (IL)-4 and IL-5. We
      examined the effects of CsA and SAR943, administered orally, on asthmatic
      responses in a rat model of chronic allergic inflammation. Sensitized Brown
      Norway (BN) rats were exposed to ovalbumin (OVA) aerosol every third day on six
      occasions. CsA (5 mg/kg/day), SAR943 (2.5 mg/kg/day) or vehicle (Neoral) was
      administered orally, once a day, from days 10 to 21 (a total of 12 doses). We
      measured eosinophilic and T-cell inflammation in the airways, proliferation of
      airway cells by incorporation of bromodeoxyuridine (BrdU) and bronchial
      responsiveness to acetylcholine. CsA had no effects, while SAR943 inhibited
      airway smooth muscle (ASM, P < 0.05) and epithelial cell (P < 0.01) BrdU
      incorporation, and the number of CD4+ T cells (P < 0.05), without effects on BHR.
      ASM thickness was not significantly increased following chronic allergen
      exposure. Therefore, CsA and SAR943 have no effect on chronic eosinophilic
      inflammation, while SAR943, but not CsA, had a small effect on the proliferation
      of ASM and epithelium.

PMID- 12807492
TI  - Anti-human immunodeficiency virus-gag CD8+ memory T cells generated in vitro from
      Listeria-immunized mice.
AB  - The goal of vaccination is the generation of immune memory, an immune state that
      permits rapid and intense recall responses to a pathogen. Considerable effort is
      being made to understand the nature of memory T cells. We report here that by
      extending the length of in vitro culture following a single restimulation with
      specific peptide, preparations of highly enriched, highly active antigen-specific
      CD8+ memory T cells could be obtained. These cultures were begun with splenocytes
      from mice primed by infection either with an attenuated strain of Listeria
      monocytogenes or vaccinia virus, both expressing the human immunodeficiency virus
      1-gag gene. In the cultures, antigen-specific cytotoxic T lymphocyte (CTL)
      activity reached a maximum at about 9 days and thereafter fell to negligible
      values. Concomitant with the fall of CTL activity, however, we observed
      enrichment for a subset of CD11ahigh antigen-specific gag-tetramerpos CD8+ T
      cells. The cells showed little or no 4-hr CTL activity, but had high delayed (18
      hr) CTL activity, and very high cytolytic activity after restimulation. They
      rapidly expressed interferon-gamma production. Their growth and survival after
      sorting was completely dependent on interleukin-2 or -15. As few as 5000 of the
      fluorescence-activated cell sorting-purified cells protected recipients against
      challenge 3 months after transfer. In response to the challenge, the cells
      repopulated lymphoid and non-lymphoid organs and showed a sizeable increase in
      number. The cells therefore demonstrate high protective activity for long periods
      of time. These cultured cells are thus a potential source of enriched natural
      memory T cells for reperfusion studies and in which the mechanisms that underlie
      the generation, differentiation and persistence of memory can be examined.

PMID- 12807496
TI  - The genetics of autoimmune endocrine disease.
AB  - The common autoimmune endocrinopathies result from an interaction between
      environmental factors and genetic predisposition. Several chromosomal gene
      regions have been shown to contribute to more than one disease, supporting the
      clinical observation that the autoimmune endocrine diseases cluster within
      individuals and families. Genetic studies have implicated the major
      histocompatability complex (MHC)-human leucocyte antigen (HLA) genes on
      chromosome 6p21, although this chromosomal region does not explain all of the
      genetic contribution to the various disorders. Non-MHC-HLA genes, including
      disease-specific loci, are beginning to be identified and the publication of the
      draft sequence of the human genome will undoubtedly expediate future discoveries.
      Combined with the establishment of large cohorts of subjects with disease and the
      development of technology capable of performing high-throughput genotyping,
      genetic studies are likely to impact on the future treatment and prevention of
      the common autoimmune endocrine diseases.

PMID- 12807497
TI  - Growth hormone therapy for syndromic disorders.

PMID- 12807498
TI  - Vitamin D deficiency in the 21st century: an unnecessary pandemic?

PMID- 12807499
TI  - Physiological but not pharmacological growth hormone tests predict adult height.

PMID- 12807500
TI  - Growth hormone secretory pattern and response to treatment in children with short
      stature followed to adult height.
AB  - OBJECTIVE: To compare the relative utility of GH stimulation tests and assays of
      spontaneous GH secretion as predictors of change in height standard deviation
      score at the end of GH treatment in children with short stature. PATIENTS AND
      METHODS: We retrospectively studied 116 children (67 boys and 49 girls) with
      subnormal growth rates and short stature, defined as a height of more than 2SD
      below the mean for age and sex. The patients were classified according to their
      pattern of findings on baseline pharmacological GH stimulation tests and a 12-h
      assay of nocturnal spontaneous GH secretion. Twenty-eight patients (24%) had
      normal hormone levels by both methods (group I); 14 (12%) had normal levels by
      stimulation tests but subnormal levels by the physiological assay (group II); 48
      (41%) had subnormal levels on pharmacological stimulation, with normal
      physiologic levels (group III); and 26 (22%) had subnormal levels by both methods
      (group IV). All children in groups II and IV, and 27 in group III, designated
      IIIb, were treated with recombinant GH at 0.7 U (0.23 mg/kg) of body weight per
      week. GH secretory patterns were related to final height SD scores and other
      growth parameters, after the patients had attained their adult stature 6.7 +/-
      2.2 years (SD) after GH evaluation. RESULTS: The five groups were similar with
      respect to mean baseline height SD scores for chronological as well as bone age.
      Whether assessed as absolute or parentally adjusted (relative) values, mean gains
      in height SD scores were significantly greater in treated patients with
      physiological hormone deficiency (groups II and IV) than in those with normal
      hormone levels (group I, untreated controls). Relative height gains were 1.03 +/-
      1.45 cm (6.6 +/- 9.28 cm) and 1.85 +/- 1.21 cm (SDS; 11.8 +/- 7.74 cm) in groups
      II and IV respectively, compared with only 0.11 +/- 0.42 cm (0.7 +/- 2.68 cm) in
      group I (P < 0.01 and P < 0.001). GH treatment failed to improve either the
      absolute or parentally adjusted final height of patients with GH deficiency by
      stimulation tests but normal levels by physiological assay. CONCLUSION: Long-term
      administration of GH to short children with normal spontaneous GH secretion is
      not associated with an appreciable increase in adult height.

PMID- 12807502
TI  - Role of protein binding in renal elimination of leptin.
AB  - OBJECTIVE: Leptin, a hormone produced by fat which signals to the brain the
      extent of fat stores, is known to be eliminated from circulation primarily by the
      kidney. The hormone circulates in both free and protein-bound forms, but there is
      little information concerning the inter-relationship of these forms of leptin, or
      which form is influenced by physiological processes such as renal elimination. We
      studied total, free and bound concentrations of leptin in ambulatory adults
      undergoing catheterization for diagnosis/management of congenital cardiac
      disease. DESIGN: Blood specimens were collected from both the arterial
      circulation and the renal vein, for determination of the fractional extraction of
      leptin resulting from a single pass through the kidney. PATIENTS: Thirteen
      subjects were studied. MEASUREMENTS: Total leptin concentrations were measured by
      radioimmunoassay, and free/protein-bound leptin concentrations were quantified by
      an high-performance liquid chromatography method. Adequacy of renal vein sampling
      was assessed by comparing the creatinine concentration of arterial and venous
      specimens. RESULTS: Mean fractional extraction of creatinine was 28 +/- 7% in the
      13 subjects studied. Fractional extraction of total leptin was 18 +/- 8%,
      significantly less than that for creatinine. Fractional extraction of total
      leptin was not related to arterial leptin concentration or the fractional
      extraction of creatinine. Both free and bound fractions of leptin were
      significantly reduced by passage through the kidney, with fractional extractions
      of 22% and 25%, respectively. Efficiency of extraction was not influenced by the
      relative proportion of free or bound leptin fractions. Leptin-binding capacity (a
      measure of the concentrations of leptin-binding proteins) was not altered by
      passage through the kidney. CONCLUSIONS: Both free and bound leptin are
      metabolically active with regard to elimination. Protein-bound leptin
      equilibrates with the free leptin fraction in circulation as the result of a
      dynamic equilibrium. The data are consistent with either glomerular filtration or
      active uptake as mechanisms of elimination. Leptin-binding proteins are
      apparently neither eliminated or produced by the kidney.

PMID- 12807501
TI  - Is ovarian and adrenal venous catheterization and sampling helpful in the
      investigation of hyperandrogenic women?
AB  - OBJECTIVE: To audit our practice of performing ovarian and adrenal venous
      catheterization and sampling in hyperandrogenic women who fail to suppress their
      elevated androgen levels following a 48-h low-dose dexamethasone suppression test
      (LDDST). We considered the technical success rate of catheterization, the extra
      information obtained in addition to the standard biochemical tests and imaging
      findings, and the impact of sampling on management decisions. DESIGN: A
      retrospective analysis of the results of all ovarian and adrenal venous
      catheterizations performed at St Bartholomew's Hospital, London, in the years
      1980-1996. PATIENTS AND METHODS: Baseline ovarian and adrenal androgens were
      measured in all women presenting with symptoms and signs of hyperandrogenism.
      Those patients who failed to suppress their elevated testosterone (T),
      androstenedione (A4) and/or dehydroepiandrosterone-sulphate (DHEAS) levels
      following a LDDST to within the normal range or to less than 50% of the baseline
      value were investigated further with adrenal computed tomography (CT), ovarian
      ultrasound, and ovarian and adrenal venous catheterization and sampling. RESULTS:
      Results were available in 38 patients. The overall catheterization success rate
      was: all four veins in 27%, three veins in 65%, two veins in 87%. The success
      rate for each individual vein was: right adrenal vein (RAV) 50%, right ovarian
      vein (ROV) 42%, left adrenal vein (LAV) 87% and left ovarian vein (LOV) 73%.
      Eight patients were found to have tumours by means of imaging (adrenal CT and
      ovarian ultrasound), three adrenal and five ovarian, seven of which underwent
      operation. In six of these patients the clinical presentation was suggestive of
      the presence of a tumour; in addition, the combination of imaging findings
      allowed the detection of suspicious adrenal and ovarian masses in all eight
      cases. The five patients with ovarian tumours had serum testosterone levels > 4.5
      nmol/l. In a further eight patients, laparotomy was performed based on a
      combination of diagnostic and therapeutic indications; in two of these patients
      the catheterization results were suggestive of an ovarian tumour. All these eight
      patients were shown histologically to have polycystic ovarian syndrome (PCOS),
      and no occult ovarian tumour was identified. None of the patients with
      nontumourous hyperandrogenism had a baseline testosterone level in excess of 7
      nmol/l (median 4.4 nmol/l, range 2.5-7 nmol/l). CONCLUSIONS: Our results suggest
      that ovarian and adrenal venous catheterization and sampling should not be
      performed routinely in women presenting with symptoms and signs of
      hyperandrogenism, even if they fail to suppress their elevated androgen levels to
      a formal 48-h LDDST. All patients presenting with symptoms and signs of
      hyperandrogenism and elevated androgen levels, and where the suspicion of an
      androgen-secreting tumour is high, should have adrenal CT and ovarian ultrasound
      imaging to detect such a tumour. Venous catheterization and sampling should be
      reserved for patients in whom uncertainty remains, as the presence of a small
      ovarian tumour cannot be excluded on biochemical and imaging studies used in this
      series alone. Its use should be restricted to units with expertise in this area.

PMID- 12807503
TI  - A novel specific bioassay for the determination of glucocorticoid bioavailability
      in human serum.
AB  - OBJECTIVE: Some patients develop side-effects even on relatively low doses of
      topically administered glucocorticoids (GCs), while others appear to be less
      sensitive to GCs. We have developed and validated a bioassay which can measure
      glucocorticoid bioavailability directly from small amounts of human serum to help
      elucidate underlying mechanisms. METHODS: We have stably transfected the human
      embryonic kidney cell line HEK293 with a plasmid expressing the glucocorticoid
      receptor, and a plasmid containing the luciferase gene preceded by three
      concatenated steroid response elements, bringing luciferase expression under
      control of the liganded glucocorticoid receptor. RESULTS: The assay, with an
      intra- and interassay coefficient of variance (CV) better than 10%, showed the
      expected difference in potency between different GCs (fluticasone propionate >
      budesonide > dexamethasone > hydrocortisone). No cross-reactivity was detected
      with other steroid hormones such as progesterone, testosterone and oestradiol.
      The bioassay easily detects the rise and subsequent fall of bioavailable GCs in
      human serum following ingestion of only 0.5 mg dexamethasone, and clearly
      reflects the diurnal cortisol rhythm. Moreover, systemic availability following
      inhalation of 2 x 250 micro g fluticasone propionate using a pressure dose
      inhaler could be demonstrated. CONCLUSIONS: This assay can be used to determine
      levels of bioavailable GCs in serum, both endogenous and administered, and thus
      may help in optimizing treatment regimens. The small amount of serum needed to
      perform an analysis makes this assay applicable even to infants.

PMID- 12807504
TI  - Diagnostic reliability of a single IGF-I measurement in 237 adults with total
      anterior hypopituitarism and severe GH deficiency.
AB  - OBJECTIVE: Within an appropriate clinical context, GH deficiency (GHD) in adults
      must be demonstrated biochemically by a single provocative test. Insulin-induced
      hypoglycaemia (ITT) and GH-releasing hormone (GHRH) + arginine (ARG) are
      indicated as the tests of choice, provided that appropriate cut-off limits are
      defined. Although IGF-I is the best marker of GH secretory status, its
      measurement is not considered a reliable diagnostic tool. In fact, considerable
      overlap between GHD and normal subjects is present, at least when patients with
      suspected GHD are considered independently of the existence of other anterior
      pituitary defects. Considering the time and cost associated with provocative
      testing procedures, we aimed to re-evaluate the diagnostic power of IGF-I
      measurement. DESIGN: To this goal, in a large population [n = 237, 139 men, 98
      women, age range 20-80 years, body mass index (BMI) range 26.4 +/- 4.3 kg/m2] of
      well-nourished adults with total anterior pituitary deficit including severe GHD
      (as shown by a GH peak below the 1st centile limit of normal response to GHRH +
      ARG tests and/or ITT) we evaluated the diagnostic value of a single total IGF-I
      measurement. IGF-I levels in hypopituitary patients were evaluated based on age
      related normative values in a large population of normal subjects (423 ns, 144
      men and 279 women, age range 20-80 years, BMI range 18.2-24.9 kg/m2). RESULTS:
      Mean IGF-I levels in GHD were lower than those in normal subjects in each decade,
      but not the oldest one (74.4 +/- 48.9 vs. 243.9 +/- 86.7 micro g/l for 20-30
      years; 81.8 +/- 46.5 vs. 217.2 +/- 56.9 micro g/l for 31-40 years; 85.8 +/- 42.1
      vs. 168.5 +/- 69.9 micro g/l for 41-50 years; 82.3 +/- 39.3 vs. 164.3 +/- 60.3
      micro g/l for 51-60 years; 67.5 +/- 31.8 vs. 123.9 +/- 50.0 micro g/l for 61-70
      years; P < 0.0001; 54.3 +/- 33.6 vs. 91.6 +/- 53.5 micro g/l for 71-80 years, P =
      ns). Individual IGF-I levels in GHD were below the age-related 3rd and 25th
      centile limits in 70.6% and 97.63% of patients below 40 years and in 34.9% and
      77.8% of the remaining patients up to the 8th decade, respectively. CONCLUSIONS:
      Total IGF-I levels are often normal even in patients with total anterior
      hypopituitarism but this does not rule out severe GHD that therefore ought to be
      verified by provocative testing of GH secretion. However, despite the low
      diagnostic sensitivity of this parameter, very low levels of total IGF-I can be
      considered definitive evidence of severe GHD in a remarkable percentage of total
      anterior hypopituitary patients who could therefore skip provocative testing of
      GH secretion.

PMID- 12807505
TI  - Physiological testosterone replacement and arterial endothelial function in men.
AB  - OBJECTIVE: The vascular effects of fluctuations in testosterone levels within the
      physiological range in otherwise healthy men are not known. We therefore aimed to
      study arterial function in hypogonadal men receiving long-term physiological
      androgen replacement therapy, at trough and peak testosterone levels. PATIENTS
      AND DESIGN: We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving
      androgen replacement therapy, each treated with 800 mg testosterone (T) depot
      preparations every 6 months. MEASUREMENTS: Serum lipid and hormone levels and
      arterial reactivity were measured, prior to (trough T) and 2-4 weeks following
      testosterone administration (peak T). Each subject therefore served as their own
      control. Vessel diameter was measured by ultrasound at rest, during reactive
      hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent
      response] and after sublingual nitroglycerin (GTN, an endothelium-independent
      dilator). RESULTS: Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum
      T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/
      23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following
      subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs.
      175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a
      significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN
      responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood
      pressure and vessel diameter measurements were also similar before and after
      testosterone administration. CONCLUSION: Physiological replacement of
      testosterone is associated with decreased endothelium-dependent dilatation, in
      hypogonadal men.

PMID- 12807507
TI  - Assessment of quality of life in adults receiving long-term growth hormone
      replacement compared to control subjects.
AB  - OBJECTIVE: There are few studies of quality of life (QOL) in adults with growth
      hormone deficiency (GHD) compared to matched control populations without GHD.
      These have shown impairments in a variety of QOL measures, which improve but do
      not normalize after short-term replacement with GH. There is little information
      on QOL in long-term treated GHD patients compared with controls without GHD.
      PATIENTS AND METHODS: A total of 120 adults with GHD who had received GH
      replacement for at least 1 year were identified from the neuroendocrine clinic.
      Patients were asked to complete eight QOL questionnaires and an Energy Visual
      Analogue Scale (VAS). Results were compared with 83 control subjects without GHD
      from the local population who agreed to complete seven of the QOL questionnaires
      (excluding Disease Impact scale) and the energy VAS. The eight questionnaires
      were a combination of generic and disease-specific questionnaires used to assess
      health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile
      (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue
      Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD)
      scale and QOL-AGHDA (assessment of GHD in adults). RESULTS: Eighty-nine patients
      returned questionnaires and 85 (71%) had complete data for analysis. The mean
      (SD) duration of GH replacement was 36.0 +/- 26.4 (range 13-159) months. Mean age
      was 43.9 +/- 15.8 years (37 males) in treated GHD patients compared to a mean age
      41.7 +/- 10.5 years (32 males) in the controls. Mean IGF-1 levels were 22.5 +/-
      13.6 nmol/l in the GHD patients and the mean dose of GH replacement was 1.2 +/-
      0.4 IU daily. Analysis of the QOL questionnaires from the GH treated patients
      revealed highly significant impairments in all measures (most P </= 0.0001,
      except life fulfilment-material, P = 0.33) compared to the control population.
      CONCLUSIONS: This large population with treated GH deficiency have significant
      impairments in multiple aspects of QOL despite replacement with GH and other
      pituitary hormones for at least 1 year (mean 3 years). It is likely therefore
      that other factors in addition to GH deficiency must influence QOL in these
      patients. Further strategies to improve QOL in these individuals should therefore
      be considered, e.g. psychological support and treatments and physical treatments
      (such as exercise programmes).

PMID- 12807506
TI  - The relation between two polymorphisms in the glucocorticoid receptor gene and
      body mass index, blood pressure and cholesterol in obese patients.
AB  - OBJECTIVE: We have recently reported that, in healthy elderly Dutch individuals,
      a N363S polymorphism in the glucocorticoid receptor (GR) gene is associated with
      higher sensitivity to low-dose dexamethasone (0.25 mg), evaluated as both
      cortisol suppression and insulin response, and with an increased body mass index
      (BMI). In the present study we investigated the role of the N363S polymorphism,
      and a BclI restriction site polymorphism in a group of Italian patients with
      severe obesity. DESIGN: Two hundred and seventy-nine patients (mean BMI 45.9 +/-
      0.9 kg/m2) were genotyped using both PCR-restriction fragment length polymorphism
      analysis and Taqman Sequence Detection System. Determination of several metabolic
      and antropometric parameters was also performed in order to correlate them to the
      genotype. RESULTS: In this group of obese patients, 13 subjects (eight female,
      five males) were heterozygous for the N363S variant (allelic frequency 2.3%) and
      had significantly higher BMI (P < 0.04), resting energy expenditure (P < 0.03)
      and food intake (P < 0.01) when compared to wild-type homozygotes. When the data
      were analysed according to sex, female heterozygotes for the N363S allele had
      significantly higher BMI (P = 0.04), resting energy expenditure (P = 0.03) and
      food intake (P = 0.008) than obese women with the wild-type 363 GR gene. Male
      carriers of this variant also had higher values for these variables although the
      differences did not reach statistical significance. A case-control study with
      homozygous wild-type obese subjects which were age-, sex- and BMI-matched,
      revealed no difference in resting energy expenditure and food intake. The allele
      frequency of the BclI variant was 27% (89 females and 41 males out of 269
      subjects). No differences in anthropometric and metabolic parameters were found
      between subjects heterozygous or homozygous for this variant GR in this obese
      population. However, when we studied the effect of the presence of the BclI
      polymorphism and the N363S variant in the same individual, we found that the
      subjects who carried both polymorphisms had a tendency towards higher systolic
      and diastolic blood pressure and significantly higher total and LDL-cholesterol
      levels (P = 0.005 and P = 0.05, respectively). DISCUSSION: Taking the results of
      this study and those obtained in the Dutch population, we speculate that
      heterozygous carriers of the N363S variant who develop obesity, may become even
      more obese, possibly because they have a hypersensitive insulin response and
      thus, via activation of lipogenesis, store fat more efficiently. Furthermore,
      these data suggest that N363S carriers who carry the BclI polymorphism as well,
      tend to have a slightly unfavourable cardiovascular profile.

PMID- 12807508
TI  - Growth without growth hormone: growth pattern and final height of five patients
      with idiopathic combined pituitary hormone deficiency.
AB  - BACKGROUND: Growth without GH has been reported in patients with organic combined
      pituitary hormone deficiency (CPHD) after resection of craniopharyngiomas and
      hypothalamic tumours or in septo-optic dysplasia. METHODS: This study describes
      the growth pattern and final height of five children (four boys, one girl) with
      idiopathic CPHD (GH, TSH, ACTH, LH and FSH) who maintained normal growth despite
      persistent GH deficiency throughout the growth period. RESULTS: Presenting
      findings were borderline small penis in two children diagnosed at ages 3 and 9
      years, and absence of pubertal signs in three adolescents diagnosed at age 12.8
      13.7 years. The latter three patients also exhibited acromegaloid features. The
      height of all patients was within the 10-25th percentiles, and weight at the 25
      50th percentiles. Although they were moderately overweight, accelerated weight
      gain was not observed. Prepubertal growth rate was 4-5 cm/year. The pubertal
      growth period, starting after initiation of sex hormone therapy (chronological
      age 15.9-16.3 years and bone age 12.5-14.5 years) continued for 4-5.5 years.
      Total pubertal growth was 6-11.7 cm with reduced growth spurt. Final height,
      which was attained at an advanced age (19-22 years), was 170-179 cm in the boys
      and 164 cm in the girl, equal to or exceeding the target height range. Repeated
      hormonal evaluations revealed undetectable GH and IGF-I levels, and no evidence
      of hyperprolactinaemia or hyperinsulinism. CONCLUSIONS: Final height attainment
      within or above target height range may occur in patients with idiopathic CPHD
      despite persistent GHD. As this was not mediated by GH, IGF-I, insulin or
      prolactin, some other growth factors probably played a growth-promoting role.

PMID- 12807509
TI  - Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey.
AB  - BACKGROUND AND OBJECTIVES: Reduced bone mineral content (BMC) and bone mineral
      density (BMD) have previously been reported in Turner's syndrome, although
      appropriate GH treatment and early induction of puberty seem to permit normal
      bone mass accumulation. Furthermore, an increased risk of fractures and
      osteoporosis have been reported in a registry study. The aim of the present study
      was to further characterize the risk of fractures in TS and to explore risk
      factors, in a historical follow-up survey based on a self-administered
      questionnaire. STUDY GROUPS: The questionnaire was issued to all females with TS
      (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age
      and geographical region. A total of 322 patients (51%) and 1169 controls (62%)
      returned the questionnaire. RESULTS: TS women were younger than C (30 years,
      range: 1-73 years vs. 34 years, range 2-82 years, P < 0.0005), smoked less often
      (17%vs. 27%, P < 0.0005), and had less frequent spontaneous menstruation (18%vs.
      86%, P < 0.0005). In contrast, they used hormonal replacement therapy (HRT) more
      often (71%vs. 7%, P < 0.0005). The median age at start of HRT was 16 years (range
      8-59 years) in TS vs. 42 years (range 12-53 years) in C (P < 0.0005). Above the
      age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS
      but only 0.2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS.
      Altogether, 77 individuals with TS had 109 fractures. The fracture risk was
      increased in TS [hazard ratio (HR, status) 1.35, confidence interval (CI) 1.04
      1.75, P = 0.025]. Time to first fracture was reduced in TS (53 +/- 2 vs. 63 +/-
      1; log-rank P = 0.03). Spontaneous menstruation was protective in females above
      13 years of age (HR: 0.70, CI 0.54-0.93, P = 0.012). A history of parental
      fractures increased the risk (HR 1.92, CI 1.62-2.27, P < 0.001). Fractures of the
      forearm was more frequent among TS (P = 0.02). CONCLUSION: The present nationwide
      survey, based on questionnaires, confirms an increased risk of early fractures in
      TS, especially in those without ovarian function and with a positive family
      history of fracture and osteoporosis. It thereby emphasizes the need for being
      vigilant with respect to BMD measurements in these patients.

PMID- 12807510
TI  - Relationship between leptin levels and bone mineral density in the elderly.
AB  - OBJECTIVE: To assess the relationship between circulating leptin levels, bone
      mineral content and density in the elderly. DESIGN: A cross-sectional study.
      PATIENTS: A cohort of 92 men and 171 women, with ages ranging from 68 to 75
      years, selected as a healthy and normal functioning group, in the city centre of
      Verona. MEASUREMENTS: Plasma leptin levels were determined in each participant.
      Body composition was evaluated with dual energy X-ray absorptiometry (DXA). Bone
      mineral content (BMC) and bone mineral density (BMD) were measured at whole-body,
      hip and femoral neck level in all subjects. RESULTS: In both men and women a
      significant relationship between fat mass and whole-body BMC or BMD was found.
      The strength of this association was consistently reduced after adjustment for
      plasma leptin. A significant association between circulating leptin levels, whole
      body, total hip and femoral neck BMC and BMD was found in both sexes. This
      association retained the statistical significance after adjustment for fat mass
      percentage, especially in women. In stepwise multiple linear regression analyses,
      leptin was shown to be a significant predictor of whole-body, total hip and
      femoral neck BMC and BMD, independently of age and the percentage of body fat in
      both sexes. The circulating levels of leptin accounted for a variance in whole
      body BMC of 8.9% in men and 18.2% in women, and in whole-body BMD of 10.6% in
      women. CONCLUSION: Our data show a significant relationship between leptin, bone
      mineral mass and density in healthy elderly men and women.

PMID- 12807511
TI  - Interleukin-2 given to asymptomatic HIV-infected individuals leads to an
      exaggerated response of the pituitary gland to the action of CRH.
AB  - BACKGROUND AND AIMS: Studies investigating the impact of interleukin-2 (IL-2) on
      the corticotroph axis have shown that IL-2 can stimulate cortisol and ACTH
      secretion. However, the site, the time course and the mechanisms of IL-2
      stimulation of the corticotroph axis are still not known. The aim of this study
      was to gain insight into the mechanisms of IL-2 stimulation of the corticotroph
      axis. PATIENTS AND METHODS: A total of 9 x 10(6) IU/day IL-2 were given to 18
      male HIV-infected patients treated with a combination of HIV antiviral drugs
      (usually two reverse-transcriptase inhibitors and one protease-inhibitor) over a
      course of 4-5 days. Seven of these 18 patients received a second course of IL-2.
      RESULTS: Cortisol levels increased significantly (P < 0.001) from baseline levels
      (427 +/- 118 nmol/l) to 746 +/- 132 nmol/l after 4 days of IL-2 therapy with a
      gradual decrease to baseline within 10 days after the end of therapy. ACTH showed
      a similar pattern rising from 5.9 +/- 1.9 pmol/l at baseline to 12.4 +/- 4.6
      pmol/l on day 4 (P < 0.001). The cortisol response after CRH application (carried
      out at 15.00 h) was significantly more pronounced at the end of IL-2 application
      (CRH test B, baseline: 330 +/- 59 nmol/l, peak 774 +/- 134 nmol/l, 135% increase)
      when compared to pretreatment (CRH test A, baseline: 226 +/- 73 nmol/l, peak 459
      +/- 103 nmol/l, 103% increase, P </= 0.0001). The cortisol response 9 days after
      the end of IL-2 administration showed a similar pattern when compared to
      pretreatment values. The ACTH response after CRH was essentially paralleled by
      the cortisol response (CRH test B, baseline: 6.1 +/- 2.8 pmol/l, peak 16.0 +/-
      4.4 pmol/l, 170% increase; CRH test A, baseline: 4.3 +/- 1.9 pmol/l, peak 9.2 +/-
      3.1 pmol/l, 110% increase, P = 0.0005). Furthermore, we observed higher ACTH and
      cortisol concentrations in the morning when compared to late afternoon values
      during treatment with IL-2 [cortisol: baseline: 426 +/- 73 nmol/l (8.00 h); 226
      +/- 73 nmol/l (15.00 h)]; day 4: [746 +/- 132 nmol/l (8.00 h); 339 +/- 59 nmol/l
      (15.00 h)]; ACTH: baseline: [5.9 +/- 1.9 pmol/l (8.00 h); 4.3 +/- 1.9 pmol/l
      (15.00 h)]; day 4: [12.4 +/- 4.7 pmol/l (8.00 h); 6.1 +/- 2.8 pmol/l (15.00 h)].
      CONCLUSION: The data from this in vivo study suggest that IL-2 most likely
      resulted in corticotroph hyperplasia leading to an exaggerated response of the
      pituitary gland to the action of CRH.

PMID- 12807512
TI  - Left ventricular mass index and ventricular septum thickness are associated with
      serum dehydroepiandrosterone-sulphate levels in hypertensive women.
AB  - OBJECTIVE: Several data indicate that endogenous sex steroids might influence
      left ventricular mass. Our aim was to examine the association between
      dehyroepiandrosterone-sulphate (DHEAS) levels and left ventricular mass index
      (LVMI) and ventricular septal thickness (VST) in pre- and in postmenopausal women
      with treated essential hypertension. PATIENTS AND METHODS: LVMI and VST were
      related to serum DHEAS in 26 pre- and in 34 postmenopausal women. The
      associations between DHEAS and LVMI, VST were adjusted for body mass index,
      duration of hypertension, systolic blood pressure, serum cholesterol and
      testosterone levels using a multiple regression model. RESULTS: In premenopausal
      women there was a significant linear correlation between DHEAS and LVMI (P <
      0.02) after adjustment for confounding variables. In contrast, DHEAS was
      inversely correlated with LVMI and VST in postmenopausal women (r = -0.49, P <
      0.02, r =-0.42, P < 0.02, respectively). These associations also remained
      significant (P = 0.04, P = 0.03, respectively) after adjustment for confounding
      variables. CONCLUSION: DHEAS might be an independent determinant of LVMI and VST.
      Its effect on the heart may depend on hormonal milieu. In premenopausal women,
      DHEAS might have androgenic effects and might enhance fibroblast proliferation;
      while during the postmenopausal period it is dominantly oestrogenic in action,
      with antiproliferative effect on cardiac cells.

PMID- 12807513
TI  - Characterization of the intracellular mechanisms mediating somatostatin and
      lanreotide inhibition of DNA synthesis and growth hormone release from dispersed
      human GH-secreting pituitary adenoma cells in vitro.
AB  - OBJECTIVE: Somatostatin is an endogenous inhibitor of hormone secretion and cell
      proliferation. Treatment with somatostatin analogues in humans causes a reduction
      in size and secretory activity of endocrine tumours, including GH-secreting
      pituitary adenomas. This study was aimed to characterize the intracellular
      mechanisms mediating the in vitro antiproliferative and antisecretory effects of
      somatostatin and its analogue lanreotide, on primary cultures of GH-secreting
      pituitary adenoma cells. DESIGN: Thirteen GH-secreting pituitary adenoma
      postsurgical specimens were analysed for somatostatin receptor (SSTR) mRNA
      expression and a subset of them was analysed in vitro for the effect of
      somatostatin on cell proliferation, assessed by means of [3H]-thymidine uptake,
      and GH release, using an immunoradiometric assay. Moreover, the intracellular
      signalling involved in such effects has been studied. RESULTS: All the adenomas
      analysed expressed at least one somatostatin receptor subtype mRNA. SSTR2 mRNA
      was identified in 77% of the adenomas, SSTR1 and SSTR3 in 69% and SSTR5 in 60%.
      Somatostatin and lanreotide inhibited cell proliferation in phorbol ester (PMA)
      stimulated conditions (10/13 adenomas), as well as after fetal calf serum (3/3
      adenomas) or IGF-I stimulation (2/2 adenomas). Conversely, GHRH or forskolin
      treatments did not significantly affect DNA synthesis in adenoma cells in the
      presence or absence of somatostatin (2/2 and 4/4 adenomas, respectively).
      Vanadate pretreatment reversed somatostatin inhibition of PMA-induced DNA
      synthesis suggesting an involvement of tyrosine phosphatase in this effect (2/2
      adenomas); this was confirmed by the direct induction of tyrosine phosphatase
      activity in two adenomas after somatostatin treatment. Somatostatin and also
      lanreotide caused significant inhibition of phorbol ester, forskolin, GHRH and
      KCl-dependent increase of GH secretion in the culture medium. Moreover, voltage
      sensitive calcium channel activity induced by 40 mm KCl depolarization in
      microfluorimetric analysis, was significantly reduced (5/5 adenomas).
      CONCLUSIONS: These data show that somatostatin and lanreotide inhibit human GH
      secreting pituitary adenoma cell proliferation and hormone release in vitro, and
      suggest that the activation of tyrosine phosphatases may represent intracellular
      signals mediating the antiproliferative effects and that the inhibition of the
      voltage-dependent calcium channels and adenylyl cyclase activities may control GH
      secretion.

PMID- 12807514
TI  - Multiple endocrine neoplasia type 1 (MEN1): genetic and clinical analysis in the
      Southern Chinese.
AB  - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad
      of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue
      and the anterior pituitary gland. DESIGN: In order to define the prevalence of
      MEN1 germ-line mutations in Southern Chinese patients with MEN1 syndrome, we
      performed direct sequencing of the entire open reading frame of the MEN1 gene for
      12 index patients and their first-degree relatives. RESULTS: Six patients had
      familial MEN1 syndrome and six had apparently sporadic disease. Nine different
      germ-line mutations at the MEN1 gene were identified, including three novel
      mutations [248-249delTT in exon 2, K559X(AAG --> TAG) in exon 10 and IVS 2nt +
      2(G --> T) in intron 2]. All patients with familial MEN1 syndrome were
      heterozygous carriers of a germ-line mutation and MEN1-related disorders were
      only evident in their first-degree relatives who also carried the mutation. All
      patients with an enteropancreatic lesion were mutation carriers and the absence
      of mutation in three apparently sporadic MEN1 patients with only
      hyperparathyroidism and pituitary microadenoma might represent the presence of
      MEN1 phenocopy. CONCLUSIONS: The finding of MEN1 germ-line mutation in all
      patients with familial MEN1 syndrome suggests that genetic screening should be
      useful in our population to identify affected individuals within a kindred and
      allow early detection of MEN1-related tumours.

PMID- 12807516
TI  - Treatment of euvolemic hyponatremia: sodium repletion or water depletion?

PMID- 12807515
TI  - The effect of cryptorchidism on inhibin B in a subfertile population.
AB  - OBJECTIVE: Prepubertal cryptorchidism may cause fertility problems in adulthood,
      due to impaired spermatogenesis. Serum inhibin B has emerged as an accurate
      marker of spermatogenesis. The aim of this study was to evaluate the impact of a
      history of cryptorchidism on serum inhibin B levels and other markers of
      spermatogenesis in subfertile men. PATIENTS AND MEASUREMENTS: In a retrospective
      study, the effect of cryptorchidism on inhibin B, FSH, LH, free testosterone,
      testicular volume and semen parameters was assessed in a case-control study
      within a population of 2613 subfertile men. Of these, 161 and 102 subjects had a
      history of, respectively, unilateral and bilateral cryptorchidism that was
      treated by orchiopexy in childhood. Hormone data were complete for 64 cryptorchid
      patients (32 unilateral and 32 bilateral). A group of 128 patients was randomly
      selected out of the remaining group of 2350 men with idiopathic subfertility. An
      additional control group consisted of 32 fertile men from the general population.
      RESULTS: In cryptorchid subfertile men, inhibin B concentrations were
      significantly lower than in noncryptorchid subfertile men and fertile men (103
      ng/l, 143 ng/l and 148 ng/l, respectively; P < 0.01). The FSH concentration was
      significantly higher in cryptorchid men vs. noncryptorchid men and controls (6.1
      IU/l vs. 3.3 and 2.9 IU/l, respectively; P < 0.01). Testicular volumes and sperm
      concentration of cryptorchid men were significantly lower than in noncryptorchid
      subfertile men (12 vs. 15 ml, P < 0.01 and 3.8 x 10(6) sperm/ml vs. 17.4 x 10(6)
      sperm/ml; P < 0.05). A significantly higher inhibin B level and sperm
      concentration was observed in men undergoing orchiopexy at an early age (1-4
      years) compared with men treated between 5 and 9 years or later (P < 0.05).
      CONCLUSION: Spermatogenesis is more impaired in cryptorchid subfertile men
      compared to men with idiopathic subfertility, as reflected by a lower inhibin B
      concentration.

PMID- 12807517
TI  - Grapefruit juice inhibits 11beta-hydroxysteroid dehydrogenase in vivo, in man.

PMID- 12807518
TI  - Nitric oxide and headache: related, but how?

PMID- 12807520
TI  - Impairment of trigeminal sensory pathways in cluster headache.
AB  - Cluster headache (CH) typically presents in clusters of attacks of intense
      (peri)orbital, unilateral pain. The distribution of the pain implies involvement
      of central and/or peripheral trigeminal pathways. These can be investigated by
      means of trigeminal somatosensory evoked potentials (TSEP) and blink reflexes
      (BR). We aimed to relate functional changes in trigeminal sensory pathways to the
      presence of cluster periods. TSEP and BR were performed in 28 episodic CH
      patients during a cluster period and repeated in 22 outside a cluster period.
      TSEP latencies (N1, P1 and N2) and amplitude (N1-P1 and P1-N2) and BR latencies
      (R1, R2 ipsilateral and R2 contralateral) were compared between sides, during and
      outside a cluster period and with healthy control data (n = 22). During a cluster
      period, N2 TSEP latencies were longer on the symptomatic side compared with the
      non-symptomatic side (27.2 +/- 3.0 ms vs. 26.3 +/- 3.4 ms, P = 0.02), and
      compared with the same side outside the cluster period (26.7 +/- 3.1 ms vs. 25.1
      +/- 3.0 ms, P = 0.01). N1, P1 and N2 latencies on the symptomatic side in
      patients during the cluster period (14.8 +/- 2.3 ms, 20.4 +/- 2.5 ms and 27.2 +/-
      3.0 ms, respectively) were significantly longer than those of healthy controls
      (13.4 +/- 1.9 ms, 18.8 +/- 2.4 ms and 25.0 +/- 2.6 ms, respectively, P < 0.03).
      Outside the cluster period, N1 latencies of both sides (15.3 +/- 2.8 ms
      symptomatic side and 15.4 +/- 2.6 ms asymptomatic side) were longer compared with
      controls (13.4 +/- 1.9 ms, P < 0.04). TSEP amplitudes and BR latencies revealed
      no significant differences. We conclude that abnormalities of the afferent
      trigeminal pathway are present in patients with cluster headache, most prominent
      during the cluster period, and on the symptomatic side. This seems primarily due
      of changes within the higher cerebral regions of the system.

PMID- 12807519
TI  - Nitric oxide pathway and response to nitroglycerin in cluster headache patients:
      plasma nitrite and citrulline levels.
AB  - Nitric oxide (NO) may participate in the mechanisms underlying vascular
      headaches, such as migraine and cluster headache (CH), by triggering neurogenic
      inflammation and activation of fibres conveying nociceptive inputs to the
      trigeminal ganglion. Similarly to migraine, the administration of the NO donor
      glyceryltrinitrate (GTN) to CH patients is a known model of inducing spontaneous
      like attacks. We carried out a GTN test (0.9 mg, sublingually) in 18 patients
      with episodic CH in active phase and 12 controls. The plasma levels of NO
      metabolite nitrites (NO2-), after conversion of nitrates to NO2-, were measured
      spectrophotometrically at baseline, at the maximum intensity of the induced
      response (or 45 min after GTN in controls), and 120 min after GTN administration.
      The basal plasma levels of L-citrulline were also assayed in patients and
      controls using high-performance liquid chromatography. Basal NO2- levels, similar
      in GTN-responsive patients and controls (48.3 +/- 10.6 and 44.6 +/- 9.5
      micromol/l, respectively) were found to be increased significantly at pain peak
      in patients (76.1 +/- 10.2 micromol/l) and after 45 min in controls (78.2 +/- 9.6
      micromol/l) (P < 0.01 vs. respective baseline values), but not after 120 min,
      without differences between groups. L-citrulline levels in basal conditions
      showed no differences between groups (patients 64.8 +/- 11.7, controls 67.3 +/-
      10.8 micromol/l). These data do not support the presence of a basal hyperactivity
      of the L-arginine-NO pathway in CH patients. Increased NO production may be of
      importance in the mechanisms leading to CH attacks, but other factors are likely
      to render CH patients hyperresponsive to NO, and ultimately to cause the
      occurrence of pain and associated features.

PMID- 12807521
TI  - Headache in schoolchildren: agreement between different sources of information.
AB  - The level of agreement between different sources of information, i.e.
      questionnaires, interviews and diaries, was evaluated in a sample of 129
      schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache
      diagnoses and headache features showed high agreement between questionnaires and
      subsequent interviews. The concordance between questionnaires and interviews for
      headache diagnoses increased, and the number of unclassified headaches decreased,
      when the International Headache Society (IHS) duration criterion was excluded.
      When comparing headache frequency reported in questionnaires and interviews with
      diary recordings, the agreement was low and the frequency higher in the diaries.
      Overall, the agreement between questionnaires, interviews and diaries was not
      related to age or gender. The questionnaire may serve as a valid source of
      information in studies of headache in schoolchildren. Prospective recordings in
      diaries provide additional information, in particular of low-intensity headache.
      In children, the IHS duration criterion should be modified or excluded.

PMID- 12807522
TI  - The family impact of migraine: population-based studies in the USA and UK.
AB  - Despite an extensive body of research on the individual burden of migraine, few
      studies have examined its impact on the family. We aimed to assess the impact of
      migraine on family life both from the perspective of those with migraine and from
      the perspective of their partners. A validated computer-assisted telephone
      interview (CATI) identified 574 people with migraine from a population sample of
      4007 in mainland England, and 568 from 4376 in Philadelphia County, in the USA.
      Migraine cases with six or more migraine attacks per year and living as married
      with partners were asked, along with their partners, to participate in this
      study. In a follow-up interview, questions were asked of the proband (i.e.
      subject identified with migraine in the survey) about the impact of migraine.
      Similar questions were also asked of the probands' partners regarding the impact
      of the proband's migraine on their participation in social, family and leisure
      activities and on family relationships. The samples from the two countries showed
      similar characteristics, and were combined. Of 389 people with migraine living
      with a household partner, 85% reported substantial reductions in their ability to
      do household work and chores, 45% missed family social and leisure activities,
      and 32% avoided making plans for fear of cancellation due to headaches. One half
      believed that, because of their migraine, they were more likely to argue with
      their partners (50%) and children (52%), while majorities (52-73%) reported other
      adverse consequences for their relationships with their partner and children, and
      at work. A third (36%) believed they would be better partners but for their
      headaches. Participating partners (n = 100) partly confirmed these findings: 29%
      felt that arguments were more common because of headaches and 20-60% reported
      other negative effects on relationships at home. Compared with subjects who did
      not have migraine regarding their work performance, a statistically significantly
      higher proportion of migraine partners were unsatisfied with work demands placed
      on them (P = 0.02), with their level or responsibilities and duties (P = 0.02),
      and with their ability to perform (P = 0.001). Results from this study show that
      the impact of migraine extends to household partners and other family members.

PMID- 12807523
TI  - Migraine headache disability and health-related quality-of-life: a population
      based case-control study from England.
AB  - The aims of this study were: (i) to compare health-related quality of life
      (HRQoL) as measured by the Medical Outcomes Study Short Form 36-Item Health
      Survey (SF-36) in a population sample of migraine headache sufferers and controls
      without migraine; (ii) to assess the relationship of HRQoL and work-related
      disability attributed to headache in a population sample. The study was conducted
      in two phases. First, a population-based, telephone interview survey of 5769
      residents of greater London, England was conducted to identify individuals with
      migraine headache (cases) and controls without migraine. In the second stage, in
      person interviews were conducted in a matched sample of 200 migraine cases and
      200 controls selected from survey respondents. At the beginning of the in-person
      interview, participants were asked to complete the SF-36. In addition, a work
      related disability score based on the telephone interview was defined as the
      number of lost work days or days when usual activity was reduced by 50% or more
      over the previous year. The disability score was trichotomized as mild (n = 98),
      moderate (n = 49), and severe disability (n = 49). Compared with controls,
      individuals with migraine headache scored significantly lower in eight of the
      nine domains of the SF-36 as well as in the overall Physical Component Summary
      (PCS) score and Mental Component Summary (MCS) score. Further, among migraine
      sufferers, each of the disability groups scored significantly lower in seven of
      the nine domains and in the summary scales. Scores showed greater reductions in
      HRQoL for the moderate and severe disability groups vs. the mild disability group
      in five of nine scales and in the Total Physical Summary score. We conclude that,
      in a population-based sample of migraine headache sufferers, individuals with
      migraine headache have lower HRQoL scores compared with controls. Moreover, among
      individuals with migraine headache, work-related disability is associated with
      lower HRQoL scores. Specifically, individuals classified with moderate to severe
      work-related disability had lower HRQoL scores than those classified with low
      disability.

PMID- 12807524
TI  - Stress, anxiety, depression and migraine.
AB  - This study investigated the intensity of stress, anxiety and depression in a
      sample of 141 migraineurs compared with a control group of 109 non-migraine
      workers matched for age and sex. Stress was measured using the Perceived Stress
      Questionnaire, and anxiety and depression using the Hospital Anxiety and
      Depression Scale. Results indicated that stress and anxiety were higher in the
      migraine group than in the control group and above the clinical level. Depression
      scores remained low in both groups, under clinical relevance. Stress is a
      primordial factor in the triggering and perpetuation of migraine attacks. The
      high score of the items 'morning fatigue', 'intrusive thoughts about work',
      'feeling under pressure', 'impatience', and 'irritability' of the stress
      questionnaire in the migraineurs is particularly significant in the intensive
      stress response. It seems necessary to manage stress to improve the daily life of
      migraineurs and to study the link between stress, anxiety and migraine.

PMID- 12807525
TI  - Pain sensitivity in pericranial and extracranial regions.
AB  - Chronic myofascial pain is very common in the general population. The pain is
      most frequently located in the shoulder and neck regions, and nociceptive input
      from these regions may play an important role for tension-type headache. The
      mechanisms leading to the frequent occurrence of muscle pain in the shoulder and
      neck regions are largely unknown. It is possible that the pain is caused by
      increased sensitivity of muscle nociceptors or by central sensitization induced
      by nociceptive input from muscle. The primary aim of the present study was to
      compare muscle pain sensitivity in the trapezius and anterior tibial muscles. The
      secondary aim was to investigate whether temporal summation, a clinical correlate
      of wind-up, is more pronounced in muscle than in skin and, if so, whether such a
      difference is more pronounced in the trapezius than in the anterior tibial
      region. Sixteen healthy subjects were included. Pressure-pain thresholds and
      electrical cutaneous and intramuscular pain thresholds were measured at standard
      anatomical points in the trapezius and anterior tibial regions. Temporal
      summation was assessed by repetitive electrical stimulation. Pressure-pain
      thresholds (P = 0.005) and intramuscular electrical pain thresholds (P = 0.006)
      were significantly lower in trapezius than in anterior tibial muscle. Temporal
      summation was present in skin and muscle of both regions (P < 0.001). The degree
      of temporal summation was significantly higher in muscle than in skin in the
      trapezius region (P = 0.02), but not in the anterior tibial region (P = 0.47). In
      conclusion, we found that muscle pain sensitivity was higher in the trapezius
      than in the anterior tibial muscle. We also demonstrated that temporal summation
      could be induced in both muscle and skin and, importantly, that temporal
      summation was significantly more pronounced in muscle than in skin in the
      trapezius but not in the anterior tibial region. These data may help to explain
      why chronic muscle pain most frequently is located in the shoulder and neck
      regions.

PMID- 12807526
TI  - Eletriptan for the treatment of migraine in patients with previous poor response
      or tolerance to oral sumatriptan.
AB  - To determine the tolerability and efficacy of eletriptan in patients who had
      discontinued oral sumatriptan due to lack of efficacy or intolerable adverse
      events (AEs) during previous clinical treatment (not a controlled trial).
      Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial
      pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel
      group, placebo-controlled multicentre study, patients with and without aura (n =
      446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n
      = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two
      hour headache response, based on first-dose, first-attack data, was 59% for
      eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for
      both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was
      rapid, with 1-h headache response rates significantly superior for E40 and E80
      vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly
      superior to placebo, based on first-dose, first-attack data, for 2-h pain-free
      response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated
      significant consistency of response, with headache relief rates at 2 h on at
      least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs
      were mild to moderate in severity and dose related. The most commonly reported
      AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce
      an effective response in patients who had previously discontinued treatment with
      sumatriptan due to lack of efficacy or side-effects.

PMID- 12807527
TI  - The headaches of Thomas Jefferson.

PMID- 12807528
TI  - SUNCT syndrome responsive to lamotrigine: documentation of the first Indian case.

PMID- 12807529
TI  - Cluster-like headache due to warfarin therapy?

PMID- 12807530
TI  - The effectiveness of spinal manipulation for the treatment of headache disorders:
      a systematic review of randomized clinical trials.

PMID- 12807534
TI  - Effects of dipole position, orientation and noise on the accuracy of EEG source
      localization.
AB  - BACKGROUND: The electroencephalogram (EEG) reflects the electrical activity in
      the brain on the surface of scalp. A major challenge in this field is the
      localization of sources in the brain responsible for eliciting the EEG signal
      measured at the scalp. In order to estimate the location of these sources, one
      must correctly model the sources, i.e., dipoles, as well as the volume conductor
      in which the resulting currents flow. In this study, we investigate the effects
      of dipole depth and orientation on source localization with varying sets of
      simulated random noise in 4 realistic head models. METHODS: Dipole simulations
      were performed using realistic head models and using the boundary element method
      (BEM). In all, 92 dipole locations placed in temporal and parietal regions of the
      head with varying depth and orientation were investigated along with 6 different
      levels of simulated random noise. Localization errors due to dipole depth,
      orientation and noise were investigated. RESULTS: The results indicate that there
      are no significant differences in localization error due tangential and radial
      dipoles. With high levels of simulated Gaussian noise, localization errors are
      depth-dependent. For low levels of added noise, errors are similar for both deep
      and superficial sources. CONCLUSION: It was found that if the signal-to-noise
      ratio is above a certain threshold, localization errors in realistic head models
      are, on average the same for deep and superficial sources. As the noise
      increases, localization errors increase, particularly for deep sources.

PMID- 12807533
TI  - Bacterial adherence to mucosal epithelium in the upper airways has less
      significance than believed.
AB  - BACKGROUND: Bacterial adherence to the upper airway epithelium is considered to
      be an important phenomenon in the pathogenesis of infections. However, the
      evidence for the hypothesis that bacterial adherence to mucosal epithelial cells
      has significance for pathogenesis of mucosal infections is based on studies using
      indirect techniques. We could find no biopsy studies with direct ocular
      observations of significant numbers of bacteria adhering to upper airway mucosal
      epithelial cells either in health or during disease. RESULTS: We studied
      specimens from healthy and infected tonsillar epithelium and specimens from the
      soft palate epithelium obtained by surgery. The specimens were examined by TEM.
      In the vast majority of specimens, we found no bacteria adhering to the
      epithelial cells in the mucosal line regardless of whether the patient was
      infected or not. Bacteria adhering to shed epithelial cells were seen in higher
      numbers. Furthermore, as bacteria are small compared to epithelial cells, we
      calculated the risk of overlooking every adhered bacteria in a section if
      bacterial adherence was such a significant phenomenon as earlier suggested. We
      found this risk to be very small. CONCLUSION: We conclude that bacterial
      adherence to mucosal surface epithelial cells is not a significant phenomenon,
      either in healthy mucosa in the upper airways or during infection. This is also
      in line with our earlier results, where we have shown that the site for the
      infectious process in pharyngotonsillitis is in the secretion on the tonsillar
      mucosal surface.

PMID- 12807535
TI  - Reexamining age, race, site, and thermometer type as variables affecting
      temperature measurement in adults - A comparison study.
AB  - BACKGROUND: As a result of the recent international vigilance regarding disease
      assessment, accurate measurement of body temperature has become increasingly
      important. Yet, trusted low-tech, portable mercury glass thermometers are no
      longer available. Thus, comparing accuracy of mercury-free thermometers with
      mercury devices is essential. Study purposes were 1) to examine age, race, site
      as variables affecting temperature measurement in adults, and 2) to compare
      clinical accuracy of low-tech Galinstan-in-glass device to mercury-in-glass at
      oral, axillary, groin, and rectal sites in adults. METHODS: Setting 176 bed
      accredited healthcare facility, rural northwest USParticipants Convenience sample
      (N = 120) of hospitalized persons GreaterEqual; 18 years old.Instruments
      Temperatures ( degrees F) measured at oral, skin (simultaneous), immediately
      followed by rectal sites with four each mercury-glass (BD) and Galinstan-glass
      (Geratherm) thermometers; 10 minute dwell times. RESULTS: Participants averaged
      61.6 years (SD 17.9), 188 pounds (SD 55.3); 61% female; race: 85% White, 8.3%
      Native Am., 4.2% Hispanic, 1.7 % Asian, 0.8% Black. For both mercury and
      Galinstan-glass thermometers, within-subject temperature readings were highest
      rectally; followed by oral, then skin sites. Galinstan assessments demonstrated
      rectal sites 0.91 degrees F > oral and FullEqual; 1.3 degrees F > skin sites.
      Devices strongly correlated between and across sites. Site difference scores
      between devices showed greatest variability at skin sites; least at rectal site.
      95% confidence intervals of difference scores by site ( degrees F): oral (0.142 -
      0.265), axilla (0.167 - 0.339), groin (0.037 - 0.321), and rectal (-0.111 -
      0.111). Race correlated with age, temperature readings each site and device.
      CONCLUSION: Temperature readings varied by age, race. Mercury readings correlated
      with Galinstan thermometer readings at all sites. Site mean differences between
      devices were considered clinically insignificant. Still considered the gold
      standard, mercury-glass thermometers may no longer be available worldwide.
      Therefore, mercury-free, environmentally safe low-tech Galinstan-in-glass may be
      an appropriate replacement. This is especially important as we face new,
      internationally transmitted diseases.

PMID- 12807537
TI  - Challenging the quality of the quality indicator, "depression without treatment".
AB  - OBJECTIVE: To assess the validity of the Minimum Data Set (MDS)-based quality
      indicator, "depression without treatment," and examine whether a nonphysician
      based educational intervention can improve the accuracy of MDS questions
      regarding depression and its treatment. SUBJECTS: All residents of a 538-bed
      urban, university affiliated, long-term-care (LTC) facility. Nursing and social
      work staff involved in completing the mood and behavior items on the MDS. DESIGN:
      Two retrospective chart review of psychotropic medications, psychiatric
      diagnoses, mental health evaluation, and treatment of all residents who were
      identified as displaying the MDS quality indicator, depression without treatment,
      before and 2 months after an educational intervention. The education consisted of
      three 1 1/2-hour sessions led by a psychiatric clinical nurse specialist to
      educate registered nurse assessment coordinators and social workers about
      psychotropic medications, clinical characteristics of psychiatric diagnoses,
      chart review, and coordination of resident medical care. RESULTS: The first MDS
      identified 66 residents as having depression without treatment. Clinical record
      review revealed that 11 of these residents were receiving an antidepressant.
      Twenty-two others were receiving a psychotropic medication consistent with their
      psychiatric diagnosis. Twenty-five of the remaining residents had not received
      mental health assessment for greater than 1 year. Two months after the
      educational intervention, 36 residents were identified as depression without
      treatment. Four of these residents were receiving an antidepressant; eight others
      were receiving a psychotropic medication consistent with their psychiatric
      diagnosis. Thirteen of the remaining residents had not received mental health
      assessment for greater than 1 year. CONCLUSIONS: This preliminary study reveals
      that the presence of the quality indicator, depression without treatment, may not
      accurately capture clinically depressed LTC residents in need of mental health
      intervention. An educational intervention may be able to assist staff in more
      accurately completing MDS questions regarding depression and its treatment.

PMID- 12807538
TI  - Nursing home experience with hospice.
AB  - OBJECTIVE: Much has been written regarding the problems of terminally ill people
      residing in nursing homes. Hospice care is one option these facilities have to
      assist in managing dying patients. The purpose of the study was to explore the
      knowledge base, experience, and attitudes of nursing home management with and
      toward hospice care. DESIGN: A descriptive study that involved phone interviews
      of a systematic random sample of management personnel in nursing homes to explore
      their experiences with hospice care. SETTING: Nursing homes. PARTICIPANTS: 60
      administrators and directors of nursing (DON) from 42 nursing homes in Missouri.
      MEASUREMENTS: Measurements included overall experience with hospice, the benefit
      of hospice to residents, specific experiences with hospice service, knowledge of
      hospice regulation and reimbursement, and perception of pain assessment skills.
      RESULTS: Results show that management personnel believe that hospice was positive
      and valuable for residents. Concerns included the frequency and availability of
      hospice services for nursing home residents, especially in rural areas. Nursing
      home management claimed that hospice was knowledgeable in pain management, yet
      when measured, pain management skills ranked 2.1 on a scale of 1 to 5 (1 being
      the best). Community and physician understanding of hospice was identified as a
      major barrier for residents. CONCLUSIONS: While the results indicate a positive
      overall experience, a number of shortcomings are identified. The study points to
      opportunities for improvement in hospice/nursing home relationships. It also
      identifies opportunities for hospices and nursing homes to educate their medical
      directors in an effort to obtain active participation in the identification of
      patients for palliative care. In addition, the need for medical directors to
      assist in the education of nursing home staff regarding hospice services and
      benefits is indicated. Specifically, medical directors can educate nursing home
      staff on care plan responsibilities with hospice patients and other regulatory
      issues.

PMID- 12807536
TI  - Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain
      homogenates.
AB  - BACKGROUND: The cyclooxygenase-2 inhibitor nimesulide is able to reduce kainate
      induced oxidative stress in vivo. Here we investigate if this effect is mediated
      by the direct antioxidant properties of nimesulide using a well-characterized in
      vitro model of kainate toxicity. RESULTS: Exposure of rat brain homogenates to
      kainate (12 mM) caused a significant (p < 0.01) increase in the concentrations of
      malondialdehyde and 4-hydroxy-alkenals and a significant (p < 0.01) decrease in
      sulfhydryl levels. High concentrations of nimesulide (0.6-1.6 mM) reduced the
      extent of lipid peroxidation and the decline in both total and non-protein
      sulfhydryl levels induced by kainate in a concentration-dependent manner.
      CONCLUSIONS: Our results suggest that the neuroprotective effects of nimesulide
      against kainate-induced oxidative stress in vivo are not mediated through its
      direct free radical scavenging ability because the concentrations at which
      nimesulide is able to reduce in vitro kainate excitotoxicity are excessively
      higher than those attained in plasma after therapeutic doses.

PMID- 12807539
TI  - Challenges in pain management among persons with AIDS in a long-term-care
      facility.
AB  - OBJECTIVE: Opiate-resistant pain has been studied in cancer for many years;
      however, its existence in end-stage acquired immunodeficiency syndrome (AIDS) has
      captured little attention. This paper examines the existence, prevalence, and
      characteristics of opiate-resistant pain among persons with AIDS receiving end of
      life care at Bailey-Boushay House, an AIDS-skilled nursing facility in Seattle,
      WA. METHODS: A retrospective chart review of consecutive discharges during 1996
      to 1999 examined patients near the end of life with advanced AIDS who had used
      opioid patient-controlled analgesia (PCA) for pain relief. The patients were
      divided into a control group (n = 97) and an opiate-resistant group (ongoing,
      severe pain with morphine use of greater than 100 mg/hr in an alert patient with
      no response to doubling doses, n = 12). The two groups were compared on the basis
      of current diagnosis of depression, history of injection drug abuse, peripheral
      neuropathy, or central nervous system involvement. RESULTS: Out of a total of 740
      AIDS admissions during the study period, 226 patients were admitted for terminal
      care. Of these, 109 utilized a PCA for pain control for at least a day before
      death. Twelve (1.6% of all admissions, 5% of terminal patients, 11% of PCA users)
      experienced opiate-resistant pain. No associations with injection drug abuse,
      central nervous system involvement, depression, or peripheral neuropathy were
      found. CONCLUSIONS: Opiate-resistant pain is rare and can be relieved by
      aggressive use of adjuvants for pain treatment. There are no distinguishing
      characteristics that are predictive of this pain syndrome among AIDS patients
      near the end of life. The recognition of,prompt attention to, opiate-resistant
      pain remains a challenge for medical providers.

PMID- 12807540
TI  - End-of-life care in dementia: a review of problems, prospects, and solutions in
      practice.
AB  - The purpose of this literature review was to assess the current state of affairs
      in end-of-life care for persons with dementia, to identify barriers to the
      provision of high-quality care, and to describe exemplary programs that have
      discovered ways to overcome these barriers. The literature reviewed included
      English-language articles published since 1990, obtained by searches of Medline,
      presentations at meetings and conferences, and the Internet. Barriers to quality
      terminal dementia care identified by this review include: (1) measurement issues
      regarding quality of care and quality of life, (2) inappropriate interventions
      stemming from lack or disregard of advance directives, cost considerations,
      healthcare system factors, and caregiver factors, (3) poor symptom management
      involving both professional and family caregivers, and (4) current health policy
      formulated by federal or state governments, insurance companies, and health
      maintenance organization. High-quality care for persons with dementia at the end
      of life is possible and is currently being provided in some settings. Further
      research into areas identified in this review is necessary if the quality of care
      being provided to this population is to improve.

PMID- 12807541
TI  - Should hypercholesterolemia be treated in frail elders?

PMID- 12807542
TI  - Rhinoscleroma in an octogenarian woman.
AB  - Rhinoscleroma, a granulomatous infection caused by Klebsiella rhinoscleromatis
      and usually afflicting young adults, was diagnosed in an 81-year-old woman.
      Treatment was started with orally administered antibiotics but was soon halted
      because of side effects. She was treated instead by local spread of a 3% rifampin
      ointment. After 6 weeks, the lesion cleared up and she improved remarkably. There
      was no recurrence during 18 months of follow-up. The current report is the second
      published case of rhinoscleroma in an elderly person and the first report on its
      cure by local treatment with a 3% rifampin ointment. This favorable experience
      contributes to the limited knowledge on rhinoscleroma in the elderly.

PMID- 12807544
TI  - The Maryland regulations: rethinking physician and medical director
      accountability in nursing homes.

PMID- 12807543
TI  - Nursing home reform and the governance of medicine: lessons from Maryland.

PMID- 12807545
TI  - Quality improvement case study: issues involving elopement of residents.

PMID- 12807547
TI  - The American Medical Directors Association's Clinical Practice Guidelines:
      introduction.

PMID- 12807548
TI  - A Clinical Practice Guideline approach to treating depression in long-term care.

PMID- 12807549
TI  - If AMDA's 1996 Clinical Guidelines for Depression were updated today, what would
      change?

PMID- 12807552
TI  - Evaluation of urinary incontinence.

PMID- 12807550
TI  - Home hospitalization.
AB  - CONTEXT: Home Hospital is a worldwide phenomenon that provides acute and subacute
      medical care in the home in an attempt to reduce the need for hospitalization.
      OBJECTIVE: To evaluate the clinical parameters of a home hospitalization program
      operating in Jerusalem for 8 years. DESIGN: The Jerusalem Home Hospitalization
      (HH) program admits inpatients for early discharge from the hospital or accepts
      patients from the community when hospitalization is imminent. A clinical profile
      of HH was obtained from a chart review. OUTCOME MEASURES: Demographic data,
      diagnoses, duration of HH and the nature of the care required by patients at the
      end of HH were surveyed in 1995. RESULTS: From November 1991 until the end of
      1999, 6297 patients over age 65 were admitted to HH. As reflected in 1995 data,
      the most common disease categories in HH were heart disease, malignancy and
      infection; 51% of HH lasted less than one month, 69% less than two. CONCLUSION:
      For 8 years, HH in Jerusalem has provided intensive home care with high levels of
      patient and family satisfaction.

PMID- 12807553
TI  - Medical director's review of urinary incontinence in long-term care.

PMID- 12807554
TI  - Pharmacotherapy of urinary incontinence.

PMID- 12807555
TI  - Nonpharmacological treatments for urinary incontinence in long-term care
      residents.

PMID- 12807556
TI  - Quality care indicators and staffing levels in a nursing facility subacute unit.
AB  - OBJECTIVE: To determine whether admissions to a subacute unit in a university
      affiliated nursing facility received equivalent care on weekdays as opposed to on
      weekends with regard to certified nursing assistant (CNA) and licensed nurse
      staffing levels. DESIGN/SETTING: A 6-month prospective analytical study conducted
      from January to July 2000. All subacute unit residents admitted to this unit were
      monitored for the presence of specific outcome measures that were correlated to
      CNA and licensed nurse staffing levels during the day shift. The setting was a 14
      bed subacute unit within a 150-bed skilled nursing facility in Atlanta, GA.
      PRIMARY OUTCOME MEASURES: The quality care indicators used were measured by
      objective data obtained prospectively from the chart and medication
      administration record. The parameters monitored included medication errors,
      falls, presence of required daily nursing note and documentation of meals eaten.
      Each resident served as his or her own control for analyses conducted between
      Tuesdays and Thursdays (weekdays) as opposed to Saturdays and Sundays (weekends).
      Median staffing ratios compared the number of CNAs and licensed nurses on duty
      between weekdays with the number who were on duty on weekends during each
      resident's stay. RESULTS: From January until July 2000, a total of 31 residents
      (25 women, 6 men) were admitted to the subacute unit. Among these residents, the
      total of weekday and weekend 24-hour reviews was equal to 1,044 resident care
      days during this 6-month study. The age range of these residents was 65 to 104
      years, with a mean age of 82.0 years. Median nurse staffing levels were lower on
      weekend than on weekday day shifts (3 vs. 4; P < 0.001). Median CNA staffing
      levels were also lower on weekend than on weekday day shifts (4 vs. 5; P <
      0.001). A total of 12 (39%) of 31 of residents were missing a total of 22 of
      1,044 total required notes. This was 2 (0.3%) of 522 for weekdays as compared
      with 20 (3.8%) of 522 for weekends (P < 0.001). With regard to documentation of
      food intake, data were omitted for 199 of 1,884 meals on weekdays as compared
      with 343 (18.2%) of 1,884 meals on weekends (P < 0.001). The rate for falls was 1
      (0.19%) of 522 on weekdays as compared with 4 (0.77%) of 522 on weekends (P <
      0.05). There was no significant difference in medication errors detected.
      CONCLUSIONS: There was a significant decrease in staffing levels for both nurses
      and CNAs during the day shift on weekends. Increased omission of required daily
      nursing notes, of meal documentation and increased falls appears to be associated
      with lower levels of weekend staffing. There were no significant differences in
      medication errors during this study. Whether the lapses in documentation actually
      resulted in a lower level of delivered care cannot be determined at this time.

PMID- 12807557
TI  - Urban-rural differences in amitriptyline use among nursing facility residents.
AB  - OBJECTIVE: To characterize patterns of amitriptyline use across the urban-rural
      continuum. DESIGN: Retrospective analysis of antidepressant drug codes and
      demographic and clinical data from the Minimum Data Set (MDS), 1994 to 1997.
      SETTING: Kansas nursing facilities. PARTICIPANTS: Facility residents aged 65 and
      older. MEASURES: A four-strata system was used to classify nursing facility
      location by county, from urban to frontier. We examined admission use and after
      admission use of amitriptyline across strata for each year separately. Unadjusted
      and adjusted odds ratios were determined for each stratum, using the urban
      stratum as the point of reference. RESULTS: Admission use of amitriptyline
      occurred in 2.3 to 4% of all admissions, and although such use was highest in the
      most rural stratum, no clear urban-rural gradient was found. In contrast,
      amitriptyline use 30 days or more after admission demonstrated modest urban-rural
      gradients in unadjusted and adjusted analyses. In 1997, when adjusted for
      demographic factors, odds ratios for amitriptyline use were 2.10 (1.54-2.87),
      1.68 (1.33-2.13), and 1.49 (1.17-1.90) for the Frontier, Rural, and Densely
      Settled Rural categories as compared with the Urban reference group. CONCLUSIONS:
      After admission to Kansas nursing facilities, rural practice patterns for
      amitriptyline use are less favorable than those in urban areas, and an urban
      rural gradient is identified. Further work is needed to identify explanatory
      patient, facility, and prescriber factors.

PMID- 12807559
TI  - Dysphagia in the elderly patient.

PMID- 12807558
TI  - Physician behavior changes following CME on the prospective payment system in
      long-term care: a pilot study.
AB  - INTRODUCTION: Physicians must understand regulatory changes in long-term care
      (LTC) and adhere to prospective payment system (PPS) guidelines for minimum data
      set (MDS), resource utilization groups (RUG) and resident assessment instrument
      (RAI) processes, documentation, and evaluation. We pilot-tested "Prospective
      Payment System in LTC," a 7.5 hour continuing medical education (CME) program
      designed to help participants make plans to implement and adhere to PPS
      guidelines and regulatory requirements. METHODS: Twelve medical directors or
      attending physicians participated. A "commitment to change" evaluation assessed
      whether participants' plans were reasonable and were implemented, and what
      barriers interfered. Participants identified 3-5 changes they intended to make.
      Three months later, participants estimated actual implementation of intended
      changes, identified obstacles to success, and rated PPS's impacts on patient
      care. RESULTS: Respondents "committed" to an average of 3.4 changes ranging from
      "better monitor transfers from LTC to acute care" to "train nurses re MDS and
      RUGs." Of 40 commitments, 0%100% progress were reported on 9 (23%) each. Mean
      implementation rate was 41%. Removing responses reporting 0% implementation, the
      rate was 53%. Common barriers were "lack of time," and "can't get attending MDs
      to meetings." MDs' ratings of PPSs' impacts were neutral (2.9 on a scale where 1
      = "PPS causes great deterioration in quality of care," 3 = "...no change." and 5
      = "...great improvement.") both immediately and 3 months post-course.
      CONCLUSIONS: Participants made reasonable plans consistent with course objectives
      and made progress implementing most intentions. LTC physicians who attended the
      CME course intended to alter their behaviors, but significant obstacles
      interfered, at least in the short term. Most thought PPS would not change the
      quality of care provided in their institutions. Future courses should address
      implementation barriers.

PMID- 12807560
TI  - Oral anticoagulation in nursing home residents.

PMID- 12807561
TI  - PQRST: A mnemonic to communicate a change in condition.

PMID- 12807563
TI  - Wrongful death.

PMID- 12807562
TI  - Overnight pulse oximetry in nursing home residents with behavior problems: case
      reports.

PMID- 12807564
TI  - Experiences with external hip protectors in homes for the aged: a report from
      Finland.
AB  - OBJECTIVE: Three observational studies were performed to examine the use and
      effectiveness of external hip protectors intended to prevent hip fractures.
      METHODS: Data were collected by: (1) questionnaire to health centers or homes for
      the aged to which hip protectors had been sent; (2) comparison of users of hip
      protectors and control subjects;(3) comparison of users of hip protectors,
      comparing time wearing versus not wearing their hip protectors for part of the
      study period. OBSERVATIONS: The use of external hip protectors is a good, cost
      effective adjunctive tool in preventing hip fractures. However, improvements in
      design are still needed to increase compliance.

PMID- 12807565
TI  - Incidence and costs of acute medical conditions in long-stay incontinent nursing
      home residents.
AB  - OBJECTIVES: To determine the incidence of acute medical conditions in incontinent
      nursing home residents, and associated costs of diagnostic testing and treatment
      DESIGN: Prospective, cohort study. SETTING: Three community nursing homes.
      PARTICIPANTS: 161 long-stay residents with urinary incontinence in (mean age 86
      years, 77% female, 92% white). MEASUREMENTS: Acute medical conditions were
      identified prospectively through medical record review based on standardized
      criteria. All diagnostic testing and treatment provided for these conditions were
      recorded, and related costs in the nursing home were assigned based on 1997-1998
      Medicare and Medicaid reimbursement. RESULTS: The highest incidences of illness
      were for dermatological conditions (107 episodes per 1000 patient-weeks,
      involving 70% of subjects), respiratory illnesses (29 per 1000 patient-weeks, 47%
      of subjects) and gas-trointestinal illnesses (24 per 1000 patient-weeks, 36% of
      subjects). Among episodes with an incidence of at least 5 per 1000 patient-weeks,
      the illness events with the highest median diagnostic testing and treatment costs
      per episode were pneumonia, acute bronchitis, and depression. Only 42 out of the
      total 1071 episodes identified resulted in a hospitalization. Significant
      predictors of higher illness incidence included greater baseline comorbidity and
      higher number of routine medications (model adjusted R-square = 0.319, P =
      0.021). CONCLUSION: Acute illness is very common among incontinent nursing home
      residents, and is generally diagnosed and treated at the nursing home site, with
      variation among conditions in associated costs. Important policy implications
      include resource allocation (including appropriate staffing patterns),
      educational and quality improvement activities, and future research and guideline
      development for the optimal management of medical conditions in the nursing home
      setting.

PMID- 12807566
TI  - Use of antihypertensive drug therapy in older persons in an academic nursing
      home.
AB  - OBJECTIVES: To determine the prevalence of hypertension and the appropriate
      treatment of hypertension in older persons in an academic nursing home. DESIGN:
      The charts of all persons aged > or = 59 years currently residing in a nursing
      home affiliated with Westchester Medical Center/New York Medical College were
      analyzed by two geriatrics fellows according to a protocol designed by one of the
      authors (W.S.A.). SETTING: An academic nursing home affiliated with Westchester
      Medical Center/New York Medical College. PARTICIPANTS: The study population
      included 96 men and 159 women, mean age 77 +/- 9 years (range, 59-100 years).
      RESULTS: Hypertension was present in 129 of 255 persons (51%). Clinical
      cardiovascular disease or target organ damage or diabetes mellitus was present in
      121 of 129 persons (94%) with hypertension. Hypertension was poorly controlled in
      21 of 129 persons (16%). Of 129 persons with hypertension, 70 (54%) were treated
      with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1
      receptor blockers, 61 persons (47%) with beta blockers, 43 persons (33%) with
      diuretics, 36 persons (28%) with calcium channel blockers, 5 persons (4%) with
      alpha blockers, and 5 persons (4%) with other antihypertensive drugs. Of 54
      persons with hypertension and diabetes mellitus, 37 persons (69%) were treated
      with ACE inhibitors or angiotensin II type 1 receptor blockers. Of 58 persons
      with hypertension and coronary artery disease, 33 persons (57%) were treated with
      ACE inhibitors or angiotensin II type 1 receptor blockers, 31 persons (53%) with
      beta blockers, 20 persons (34%) with diuretics, 18 persons (31%) with calcium
      channel blockers, 2 persons (4%) with alpha blockers, and 4 persons (7%) with
      other antihypertensive drugs. Of 31 persons with hypertension and heart failure,
      only 5 persons (16%) had measurement of left ventricular ejection fraction. Of 31
      persons with hypertension and heart failure, 30 persons (97%) were treated with
      diuretics, 21 persons (68%) with ACE inhibitors or angiotensin II type 1 receptor
      blockers, 18 persons (58%) with beta blockers, and 8 persons (26%) with calcium
      channel blockers. CONCLUSIONS: Of older persons with hypertension in an academic
      nursing home, 16% had poor control of their hypertension. There was overuse of
      calcium channel blockers and alpha blockers and underuse of diuretics, beta
      blockers, and ACE inhibitors in treating hypertension. Physician education needs
      to be intensified to provide better medical care of older persons with
      hypertension through the use of optimal doses of drugs found to be effective and
      safe by evidence-based studies.

PMID- 12807568
TI  - Tardive dyskinesia in elderly patients: an update.
AB  - The use of antipsychotic agents can be limited by side effects, particularly
      extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). These neurologic
      movement disorders can occur early in the course of treatment (often as EPS) or
      as a more latent effect (TD). TD can be debilitating, and several patient-related
      and treatment-related factors have been associated with an increased risk for its
      development. Of these, older age has been strongly linked to TD. The advent of
      novel antipsychotics for the treatment of schizophrenia and severe behavioral
      disorders permits the use of such agents with reduced risk of EPS and TD. Most
      clinical trials of the novel antipsychotics have enrolled younger patients, but
      some data on their efficacy and safety in the elderly are now available. This
      article reviews the relationship between TD and aging and its treatment in
      elderly patients.

PMID- 12807567
TI  - Calcium and vitamin D supplementation in nursing home residents.

PMID- 12807569
TI  - Are all pressure ulcers avoidable?
AB  - A quality of care debate centers on whether pressure ulcers result from factors
      largely dependent on caregivers, or whether pressure ulcers result from factors
      associated with patient morbidity. A reduction in incidence, defined as the
      development of a new pressure ulcer, is the focus of prevention strategies. Yet
      epidemiological data demonstrates a stability in the incidence of pressure ulcers
      despite drastic improvements in understanding of pressure ulcers, increased
      regulatory oversight, and improvements in technologies available for prevention
      of pressure ulcers. The explanation for this stable incidence of pressure ulcers
      includes a failure of known effective preventive treatment to be applied or the
      failure of prevention strategies to be effective in spite of being applied. No
      intervention strategy has been reported that consistently and reproducibly
      reduces the incidence of pressure ulcers to zero. The published data on
      prevention of pressure ulcers do not support an assumption that all pressure
      ulcers are preventable. An effective prevention strategy demonstrated to
      eliminate pressure ulcers across healthcare settings is lacking.

PMID- 12807570
TI  - Oral anticoagulation in nursing home residents.

PMID- 12807571
TI  - Use and management of chronic urinary catheters in long-term care: much
      controversy, little consensus.
AB  - In long-term care facilities, 5 to 15% of residents have chronic urinary
      catheters in place. Catheters are commonly used for urinary retention,
      incontinence control, wound management, and patient comfort. The appropriate use
      and management of these devices continues to be studieddebated. Transurethral
      catheters are more common than suprapubic or condom-type devices, but no method
      has been proven superior for use in long-term care. Although some catheter
      management and infection control measures are well supported in the medical
      literature, clinical practices still vary widely. The accurate diagnosis of
      urinary tract infection can be especially challenging in this population. Many
      aspects of catheter care remain to be clarified, and further research based in
      chronic care settings is needed.

PMID- 12807572
TI  - A Clinical Practice Guideline approach to treating depression in long-term care.

PMID- 12807573
TI  - Responsibilities of attending physicians in long-term care facilities.

PMID- 12807574
TI  - Quality improvement case study: issues involving elopement of residents.

PMID- 12807576
TI  - Assessing antipsychotic effectiveness in dementia with the factor structure of
      the Psychogeriatric Dependency Rating Scale (PGDRS).
AB  - OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) impact
      patient functioning, caregiver burden, and transition to structured living
      environments. The purpose of this study was to use the derived factor structure
      of the Psychogeriatric Dependency Rating Scale (PGDRS) to retrospectively assess
      short-term antipsychotic effectiveness. SETTING AND MEASUREMENT: A principal
      components factor analysis was conducted with PGDRS admission ratings for a large
      national sample of hospitalized dementia patients (N = 2747). Changes in
      calculated factor scores (admission to discharge) were used to compare
      effectiveness for a subset of patients treated with one of three antipsychotic
      agents: haloperidol, olanzapine, or risperidone. RESULTS: A four-factor solution
      accounted for almost 60% of rating variance. Factors were interpreted as
      disruptive overactivity, thought/communication disorder, interpersonal
      aggressiveness, and destructiveness. Medication effects (adjusting for group
      differences) were found for only the Interpersonal Aggressiveness factor.
      Improvement in this factor score was significantly greater in the olanzapine
      group. CONCLUSIONS: Findings suggest that these four PGDRS factors can provide a
      useful framework for symptom assessment and for targeted treatment.

PMID- 12807578
TI  - Effectiveness of a group exercise program in a long-term care facility: a
      randomized pilot trial.
AB  - OBJECTIVE: The purpose of this pilot was to determine whether a strength and
      flexibility program in frail long-term care facility (LTC) residents would result
      in improved function. DESIGN: A prospective, randomized, controlled,
      semicrossover trial was designed with participants assigned either to group
      exercise (EX) or recreational therapy (C). In the EX group, the intervention
      continued for 1 year. In the C group, recreation continued for 6 months; these
      controls were then crossed over to the same exercise intervention as the EX group
      and followed for an additional 6 months. Functional outcomes were measured at
      baseline and 3, 6, 9, and 12 months for both groups. SETTING: A LTC facility,
      which included both assisted living (AL) and nursing home (NH) residents.
      PARTICIPANTS: Twenty frail residents (5 from NH, 15 from AL) aged 75 to 99 years
      at one LTC facility. INTERVENTION: After random group assignment, the EX group
      met 1 hour three times per week. An exercise physiologist and LTC staff conducted
      sessions which included seated range of motion (ROM) exercises and strength
      training using simple equipment such as elastic resistance bands (therabands) and
      soft weights. The C group met three times per week and participated in activities
      such as painting during the first 6 months, before crossing over to exercise.
      MEASUREMENTS AND METHODS: Objective measures of physical and cognitive function
      were obtained at baseline and 3, 6, 9, and 12 months using the timed get-up-and
      go test (TUG), Berg balance scale, physical performance test (PPT), and mini
      mental status exam (MMSE). Because we were interested in the impact of exercise
      on multiple endpoints and to protect the type I error rate, a global hypothesis
      test was used. RESULTS: There was a significant overall impact across the four
      measures of the exercise intervention (P = 0.013). Exercise benefit as indicated
      by the difference between exercise and control conditions showed exercise
      decreased TUG by 18 seconds, which represents an effect size (in standard
      deviation units) of 0.50, increased PPT scores by 1.3, with effect size = 0.40,
      increased Berg scores by 4.8, with effect size of 0.32, and increased MMSE by
      3.1, with effect size = 0.54. Except for the Berg, 90% confidence intervals on
      these exercise effects excluded 0. CONCLUSION: Frail elderly in a LTC facility
      were able to participate and benefit from a strength training program. The
      program was delivered with low-cost equipment by an exercise physiologist and LTC
      staff. The advantage of such a program is that it provides recreational and
      therapeutic benefits.

PMID- 12807577
TI  - Urban-rural patterns of increasing antidepressant use among nursing facility
      residents.
AB  - OBJECTIVE: To characterize changing patterns of antidepressant use in nursing
      facilities across the urban-rural continuum during the mid-1990s. DESIGN:
      Retrospective analysis of antidepressant drug codes and demographic/clinical data
      from the Minimum Data Set (MDS) 1994 to 1997. SETTING: Kansas nursing facilities.
      PARTICIPANTS: Facility residents aged 65 and older. MEASUREMENTS: We examined (1)
      admission use and (2) after-admission use for newer and older antidepressants for
      each year separately, using a 4-stratum system to classify nursing facility
      location by county, from urban to most rural. Incidence rate ratios were
      determined for antidepressant use in each stratum using the urban strata as the
      reference. RESULTS: Remarkable increases in use of newer antidepressants were
      seen over time in all strata, but use was highest in the urban area. Modest urban
      rural gradient effects attenuated over time and were not consistently seen across
      analyses and years. Tricyclic antidepressant (TCA) use remained largely unchanged
      over time and at much lower rates than newer agents. However, TCA use was also
      modestly higher in urban areas. Differences were clearer for use after admission,
      in contrast with admission use patterns. CONCLUSIONS: Newer antidepressants were
      rapidly adopted across the urban-rural continuum from 1994 to 1997. Marked
      increases in both admission and after-admission use of newer antidepressants were
      seen. Both newer and older antidepressants were used at modestly higher rates in
      urban areas. Further work is needed to elucidate the patient, prescriber, and
      facility factors that explain these prescribing patterns.

PMID- 12807579
TI  - The cost of treating pneumonia in the nursing home setting.
AB  - OBJECTIVE: To determine the costs of treating pneumonia in the nursing home
      setting and explore what factors are most responsible for that cost with a view
      to reducing cost. DESIGN: Prospective cohort study. SETTING: Thirty-six Missouri
      nursing homes participating in the study from April 1997 through September 1998.
      PARTICIPANTS: Nursing home residents with pneumonia who were not hospitalized (n
      = 502). We included residents evaluated in the emergency department (ED) and
      returned to the nursing home without admission. MEASUREMENTS: Residents were
      evaluated by project nurses. Examination findings, diagnostic testing, and
      treatment information for 30 days following evaluation were abstracted from
      medical records. Bills were obtained for individuals evaluated in the ED.
      RESULTS: There was significant variation in the cost of treating pneumonia in
      nursing homes. Episode costs were higher for residents seen in the ED of a
      hospital, residents with decubitus ulcers, black residents, and residents in
      larger facilities. Although total episode costs were related to illness severity,
      most of the variation in cost is not explained by resident or illness
      characteristics. The average cost for treating an episode of pneumonia in the
      nursing home, over and above usual care, was $458. CONCLUSIONS: There is wide
      variation in treatment for residents with similar clinical presentations. For
      residents at low risk of mortality, using less expensive antibiotics and reducing
      ED evaluation could result in cost reductions, although the effect on outcomes is
      unknown.

PMID- 12807580
TI  - Hospitalization of the nursing home patient.

PMID- 12807581
TI  - Decreasing the incidence of falls in the nursing home in a cost-conscious
      environment: a pilot study.
AB  - OBJECTIVE: To evaluate the prevalence of falls and determine the effectiveness of
      three simple interventions in decreasing the number of falls in a frail nursing
      home population. METHODS: Charts and records were reviewed to determine the
      prevalence of falls. Falls were tracked according to severity and time and place
      of occurrence. Interventions were made in three areas: (1) Environmental: Room
      furniture was repositioned. (2) Staffing: One additional staff member was added
      (by schedule change) at the time when the incidence of falls was highest. (3)
      Restorative activity program: A program was added at the time when the incidence
      of falls was high. Falls data were again collected after the intervention.
      RESULTS: Before intervention, there were 479 falls resulting in 16 fractures; 221
      (46%) of the falls occurred during the 3-11 shift and resulted in 63% (n = 10) of
      the fractures. After intervention, there were a total of 299 falls and 8
      fractures. This represents a statistically significant 38% reduction in the total
      number of falls and a 50% reduction in the total number of fractures during this
      period. Additionally, falls on the evening and night shifts were significantly
      reduced from 221 to 115 falls and 91 to 29 falls, respectively. CONCLUSION: Our
      interventions may have contributed to a decrease in the overall number of falls
      and resultant fractures. Our data suggest these simple, practical, and easy to
      implement methods may positively impact the number of falls in other institutions
      as well.

PMID- 12807582
TI  - Methadone maintenance: its future in skilled nursing facilities.
AB  - The number of geriatric residents in skilled nursing facilities (SNF) receiving
      methadone maintenance is likely to increase as the drug abusing population ages.
      Currently, facilities specializing in the care of human immunodeficiency virus
      (HIV) diseases are predominantly affected, but over the next decade this will
      change. Residents on methadone have unique needs based on their drug history and
      current treatment demands and will present new challenges for the affected
      institutions. There are no current publications or data in the literature
      exploring the use of methadone for the aging nursing home patient. Further
      investigation is necessary so that these residents are appropriately cared for.

PMID- 12807583
TI  - Advance care planning in long-term care facilities.
AB  - Residents of long-term care facilities are at risk of serious medical illnesses
      and being unable to express choices when difficult treatment decisions must be
      made. Advance care planning (ACP) allows residents to consider, make, and
      communicate their preferences for how medical decisions should be made if they
      are unable to participate in the decision-making process. This article reviews
      the three steps in ACP: consideration of options and expression of values,
      communication of decisions, and documentation of the choices. The article defines
      and describes the particular value of ACP in long-term care facilities, reviews
      the literature on successful ACP programs in long-term care, and concludes with
      practical suggestions on how to develop and implement ACP programs.

PMID- 12807584
TI  - Ethics corner: cases from the Hebrew Rehabilitation Center for aged-friends.

PMID- 12807585
TI  - Comments on the cases of Ms. S. And Ms. B.

PMID- 12807586
TI  - Assessing antipsychotic effectiveness in dementia: a factor analysis approach.

PMID- 12807587
TI  - The sky is falling.

PMID- 12807588
TI  - Reforming the care of our elders: reflections on the role of reimbursement.

PMID- 12807589
TI  - Improving pneumococcal vaccination rates.

PMID- 12807590
TI  - Pain Assessment for the Dementing Elderly (PADE): reliability and validity of a
      new measure.
AB  - OBJECTIVES: To establish the reliability and validity of a measure to assess pain
      in individuals with advanced dementia. DESIGN: Sixty-five residents of long-term
      care facilities were assessed using a new rating tool, the Pain Assessment for
      the Dementing Elderly (PADE), in two separate studies: (1) Residents were
      assessed simultaneously by two different raters, at Time 1 and 2, to establish
      interrater reliability, stability, and internal consistency. (2) Validity was
      established by assessing the correlation between an agitation scale and the PADE;
      by comparing groups with pain as a significant clinical factor (as assessed by an
      independent rater) versus not a significant factor, and by assessing individuals
      receiving versus not receiving psychoactive medications. SETTING: Four different
      long-term care facilities, three skilled nursing facilities, and a locked
      dementia assisted-living facility. PARTICIPANTS: Twenty-five residents of long
      term care facilities with advanced levels of dementia in Study 1, and 40
      residents with similar level of dementia in Study 2; 42% of the total sample were
      rated as having significant painful conditions. MEASUREMENTS: For Study 1, the
      PADE was administered; for Study 2, the PADE and the Cohen-Mansfield Agitation
      Inventory (CMAI) were administered. RESULTS: Reliability coefficients were
      adequate (interrater = 0.54-0.95; stability = 0.70-0.98; and internal consistency
      = 0.24-0.88). Validity coefficients were likewise encouraging, with the PADE
      demonstrating the expected relationship with a measure of agitation. The PADE
      also differentiated between groups that were independently judged to suffer
      clinically problematic pain versus those who were not. CONCLUSION: The PADE is a
      reliable and valid tool to assess pain in dementing elderly residents of long
      term care facilities.

PMID- 12807591
TI  - Development and psychometric evaluation of the Pain Assessment in Advanced
      Dementia (PAINAD) scale.
AB  - OBJECTIVES: To develop a clinically relevant and easy to use pain assessment tool
      for individuals with advanced dementia that has adequate psychometric properties.
      DESIGN: Instrument development study using expert clinicians and behavioral
      observation methods. Measurement of sensitivity of the instrument to detect the
      effects of analgesic medications in a quality improvement activity. SETTING:
      Inpatient dementia special care units in a Veterans Administration Medical
      Center. PARTICIPANTS: Nineteen residents with advanced dementia who were aphasic
      or lacked the ability to report their degree of pain and six professional staff
      members. Additionally, data from medical records of 25 residents who were
      receiving pain medications as required (PRN) were collected. MEASUREMENTS: Based
      on the literature review, related assessment tools and consultation with expert
      clinicians, a five-item observational tool with a range of 0 to 10 was developed.
      The tool, Pain Assessment in Advanced Dementia (PAINAD), was compared with the
      Discomfort Scale and two visual analog scales (discomfort and pain) by trained
      raters/expert clinicians in the development study, and used for detection of
      analgesic efficacy in a quality improvement activity. RESULTS: Adequate levels of
      interrater reliability were achieved between dyads of the principal investigator
      with each clinical research rater and between two raters. PAINAD had satisfactory
      reliability by internal consistency with a one factor solution. PAINADthe
      Discomfort Scale-Dementia of Alzheimer Type (DS-DAT) were significantly
      correlated, providing evidence of construct validity. PAINAD detected
      statistically significant difference between scores obtained before and after
      receiving a pain medication. CONCLUSIONS: The PAINAD is a simple, valid, and
      reliable instrument for measurement of pain in noncommunicative patients. Since
      the patient population used for its development and testing was limited to a
      relatively small number of males, further research is needed before it can be
      universally recommended.

PMID- 12807592
TI  - A profile of residents admitted to long-term care facilities for end-of-life
      care.
AB  - INTRODUCTION: Permanent placement in a Long-Term-Care (LTC) facility following
      hospitalization or when staying at home is no longer a viable option is the
      reality for a growing number of Americans. When death is imminent, the
      specialized knowledge and skill of the hospice team is required and accepted as
      an important component of end-of-life (EOL) care. The provision of appropriate
      care at the EOL is contingent on accurate identification of those residents who
      are approaching the final stage of life. This study describes the prevalence,
      profile, and survivorship of residents admitted to LTC facilities, using the
      Minimum Data Set (MDS) designation of being at the EOL. METHODS: A descriptive,
      correlational, retrospective cohort design was used to analyze all residents
      admitted to certified LTC facilities with hospice contracts in Missouri in 1999.
      Variables for analysis were selected from the MDS items that are clinically
      relevant for those residents at the EOL, for example, pain, incontinence, skin
      condition, activities of daily living (ADLs), depression, and weight loss. In
      addition, items regarding advance directives, use of special treatments, and
      diagnoses were selected because they are important to the care of residents at
      the EOL. RESULTS: Of 492 eligible facilities, 159 were confirmed as providing
      hospice care. Of 9615 admissions to these facilities, 432 (4.5%) met the EOL care
      definition; half of these were receiving specialist hospice care. The EOL
      residents were distinguishable in terms of symptoms. Median survival time for EOL
      admissions was 33 days. At 6 months, only 17% of EOL admissions remained in the
      facility. CONCLUSIONS: Residents designated as EOL who are admitted to LTC are a
      distinct group from other new residents, with identifiable needs requiring
      specialist attention. Accurate recognition that EOL is imminent is required for
      the development of appropriate strategies and resources for care.

PMID- 12807593
TI  - Staff perceptions of end-of-life care in long-term care.
AB  - OBJECTIVE: Although residential care/assisted living facilities and nursing homes
      have increasingly become a significant site of death for older Americans, little
      is known about staff perceptions of end-of-life care, perceived need for
      improvement in care, and differences by type of setting. DESIGN, SETTING, AND
      PARTICIPANTS: Ninety-nine staff provided their perceptions of end-of-life care
      for 99 decedents from 74 residential care/assisted living facilities and nursing
      homes in four states as part of a larger cohort study. Staff were interviewed
      retrospectively regarding care provided during residents' last month of life.
      MEASUREMENTS: Staff reported on 11 areas of end-of-life care, describing the
      importance of each area and the level of improvement they felt was indicated.
      Weighted "need for change" scores were calculated as the product of perceived
      importance and need for improvement. RESULTS: Both residential care/assisted
      living and nursing home staff reported a need for more staff education and
      nursing assistant time, as well as more use of volunteers. The two lowest ranked
      items for both facility types were involvement of hospice and encouragement for
      staff to attend funeral services. Nursing home staff perceived a greater need for
      improvement than residential care/assisted living staff in all 11 areas.
      CONCLUSION: Results underscore the staffing demands of end-of-life care across
      facility types, and staff desires to be able to provide quality care throughout
      the dying process.

PMID- 12807594
TI  - Tube-feeding versus hand-feeding nursing home residents with advanced dementia: a
      cost comparison.
AB  - OBJECTIVE: To compare the costs associated with caring for severely demented
      residents nursing homes with and without feeding tubes. DESIGN: Retrospective
      cohort study. SETTING: A 700-bed long-term care facility in Boston Participants:
      Nursing home residents aged 65 years and over with advanced dementia and eating
      problems for whom long-term feeding tube had been discussed as a treatment
      option. MEASUREMENTS: Costs were compared over the 6 months that followed the
      tube-feeding decision for those residents who did and did not undergo feeding
      tube placement for the following items: nursing time, physician assessments,
      food, hospitalizations, emergency room visits, diagnostic tests, treatment with
      antibiotics and parenteral hydration, and feeding tube insertion. RESULTS: Twenty
      two subjects were included, 11 were tube-fed (mean age 84.3 years +/- 6.0) and 11
      were hand-fed (mean age 90.2 years +/- 9.1). The daily costs of nursing home care
      were higher for the residents without feeding tubes compared with residents with
      tubes ($4219 +/- 1546 vs $2379 +/- 1032, P = 0.006). Nonetheless, Medicaid
      reimbursement to nursing homes in at least 26 states is higher for demented
      residents who are tube-fed than for residents with similar deficits who are not
      tube-fed. Costs typically billed to Medicare were greater for the tube-fed
      patients ($6994 +/- 5790 vs. $959 +/- 591, P < 0.001), primarily because of the
      high costs associated with initial feeding tube placement and hospitalizations or
      emergency rooms visits for the management of complications of tube-feeding.
      CONCLUSIONS: Nursing homes are faced with a potential fiscal incentive to tube
      feed residents with advanced dementia: tube-fed residents generate a higher daily
      reimbursement rate from Medicaid, yet require less expensive nursing home care.
      From a Medicare perspective, tube-fed patients are expensive due to the high
      costs associated with feeding tube placement and acute management of
      complications. Further work is needed to determine whether these potential
      financial incentives influence tube-feeding decisions in practice.

PMID- 12807596
TI  - Electroconvulsive therapy in the long-term care setting: an overview of
      controversies in practice.

PMID- 12807595
TI  - Acute diarrhea in frail elderly nursing home patients.

PMID- 12807598
TI  - Comments on the case of Mrs. R.

PMID- 12807597
TI  - Ethics corner: cases from the Hebrew rehabilitation center for aged-truth or
      consequences.

PMID- 12807599
TI  - Assessing pain in cognitively impaired nursing home residents: the state of the
      science and the state we're in.

PMID- 12807600
TI  - Should reimbursement rates be increased for feeding assistance in nursing homes?

PMID- 12807602
TI  - Antibiotic prescribing and outcomes following treatment of symptomatic urinary
      tract infections in older women.
AB  - OBJECTIVE: To describe antibiotic prescribing patterns for the treatment of
      urinary tract infections (UTI) among older women female long-term care facility
      residents and evaluate factors associated with adverse outcomes METHODS:  STUDY
      DESIGN: Population-based retrospective cohort study. Population and sampling
      frame: All female residents of Olmsted County, Minnesota, aged 65 years and
      older, who were treated for urinary tract infections during calendar year 1996
      were included in the study. DATA COLLECTION: Subjects' complete medical records
      were reviewed and abstracted. Data collected included age, weight, serum
      creatinine, antibiotic treatment including dosage and duration, as well as
      retreatment and adverse drug events. RESULTS: A total of 196 subjects, ranging in
      age from 65 to 98 years, were diagnosed with UTI during calendar year 1996. Forty
      four subjects were nursing home residents, and 152 resided in the community. The
      odds of prolonged antibiotic therapy (7 days or more) were 83 times higher among
      nursing home residents (Odds ratio = 82.7, 95% Confidence Interval, 11.1-617.7).
      The odds of receiving treatment for 10 days or longer were 5 times higher among
      nursing home residents compared to community subjects. The odds of underlying
      renal impairment necessitating dosage reduction were 3.6 times higher among
      nursing facility residents. Nursing facility residents were 7.3 times more likely
      to be treated with excessive dosages of antibiotics, 9.6 times more likely to
      experience adverse drug events, and 2.6 times more likely to receive retreatment
      for persistent or recurrent symptoms within one week of antibiotic
      discontinuation, compared to community subjects with UTI. CONCLUSIONS: Nursing
      home residents with UTI are treated for longer durations than community elderly.
      They experience a greater likelihood of receiving antibiotics in excessive
      dosage, a greater likelihood of adverse drug events, and a greater likelihood of
      retreatment compared with community subjects with UTI.

PMID- 12807601
TI  - Pneumococcal vaccination in pennsylvania nursing homes: factors associated with
      vaccination level.
AB  - OBJECTIVES: To determine the levels of knowledge and beliefs about pneumococcal
      disease and the pneumococcal polysaccharide vaccine (PPV), the level of PPV use,
      PPV-related practices, and factors associated with PPV use in Pennsylvania's
      nursing homes. DESIGN/SETTING: A 68-item, cross-sectional survey of Nursing
      Directors at a random sample of PA nursing homes (291) was conducted between
      April and June 1999. Survey results and facility characteristics were used to
      describe vaccination practices, estimate the vaccination level and determine
      through bivariate analysis, associations between vaccination level and facility
      characteristics and practices. RESULTS: Respondents are knowledgeable about PPV
      and recommendations for its use but less knowledgeable about financial
      reimbursement. Pneumonia is believed to be a serious threat to nursing home
      residents; PPV is thought to be important, effective, cost-effective, and safe
      for use in nursing homes. The estimated PPV rate is 49%, and vaccination
      practices are variable. Factors associated with higher vaccination level include:
      knowledge of financial reimbursement, strong belief in the importance of
      vaccinating residents and the effectiveness of the vaccine, practices related to
      policies, assessment, consent and orders, and organizational factors of size,
      ownership, average length of stay, and identification of a staff "vaccine
      advocate." CONCLUSION: Staff members are knowledgeable about the vaccine and
      believe it should be used in nursing homes. Efforts aimed at improving
      vaccination rates should concentrate on examples of effective vaccination
      programs and practices rather than basic information about the vaccine.
      Development of institutional policies, which guide vaccination practice and
      institutionalize the use of automated patient management systems that prompt
      staff to assess vaccination status and order vaccination, could have considerable
      impact in meeting the recommendation for vaccination of nursing home residents.

PMID- 12807604
TI  - Barriers to timely care of acute infections in nursing homes: a preliminary
      qualitative study.
AB  - BACKGROUND AND OBJECTIVES: During a large prospective study of lower respiratory
      infections in nursing home residents, project staff observed that in some
      facilities there was consistent difficulty in obtaining timely identification of
      potential subjects. Starting with this motivation, we conducted a preliminary
      qualitative study to investigate the process of illness identification and
      initiating management in episodes of acute infection. We sought factors promoting
      timely or delayed identification and treatment of acute infections among nursing
      home residents. DESIGN: Qualitative study using focus groups and in-depth semi
      structured interviews of residents, nurses, and physicians involved in episodes
      of acute-illness care in nursing home residents. SETTING: Four nursing homes
      participating in a longitudinal study of the course and outcomes of lower
      respiratory infection. PARTICIPANTS: Focus groups included nurses and physicians
      with experience in nursing home care. Interviews were conducted with those
      involved in six episodes of acute illness. Interviewees included four nursing
      home residents (two others were not cognitively intact), seven nurses, and six
      physicians or their staff. DATA ANALYSIS: Identifying themes from focus group
      contributions and content analyses of interviews. RESULTS: We identified a four
      stage model describing illness identification and management. Content analysis of
      interview transcripts revealed 22 factors that influenced timeliness of effective
      care with communication problems commanding the central focus. Barriers included:
      (1) failure of the communication medium; (2) evening or weekend illness onset
      with concomitant difficulty in contacting an on-call physician; (3) clinical
      decision-makers who interact through intermediaries; (4) the communication of
      inappropriate or inaccurate information; (5) inadequate information transfer at
      shift changes; and (6) prior relationship between staff nurse and physician.
      CONCLUSION: Effective identification and management of acute infections requires
      successful communication at multiple levels; however, breakdowns are common. Our
      model provides a framework for improving acute illness care in nursing homes,
      which offers important insights potentially useful in quality improvement
      activities in nursing homes and may facilitate further research.

PMID- 12807605
TI  - Preventing assaults by nursing home residents: nursing assistants' knowledge and
      confidence--a pilot study.
AB  - OBJECTIVE: To describe the frequency and context of assaults against nursing
      assistants (NAs) from residents and to describe NAs' beliefs about their violence
      prevention knowledge and self-efficacy to prevent assaults from residents.
      DESIGN: Survey. SETTING: Six nursing homes. PARTICIPANTS: A total of 138 nursing
      assistants. MEASUREMENTS: NAs completed two investigator-developed surveys, the
      Demographic and Employment Questionnaire and the Knowledge and Self-Efficacy
      Survey. The Demographic and Employment Questionnaire included questions about
      race, gender, age, and education, current and previous employment, number of
      residents usually assigned, frequency of assaults, and training on workplace
      violence. On the Knowledge and Self-Efficacy Survey, the participants used a five
      point Likert scale to rate their knowledge and confidence in recognizing and
      preventing assaults from residents. RESULTS: Assaults against nursing assistants
      from residents in nursing homes were common; 59% stated they were assaulted at
      least once a week and 16% stated they were assaulted daily. Fifty-one percent
      stated that they had been injured in their lifetime from an assault from a
      resident, and 38% of those injured received medical attention for an injury. On
      the Likert items, nursing assistants reported that they believed they had the
      most knowledge (mean = 3.76) and confidence (mean 3.81) in their ability to
      recognize when a resident is agitated or becoming aggressive. In comparison, NAs
      rated lower their knowledge (mean = 3.45) and confidence in their ability (3.50)
      to keep residents from becoming agitated or aggressive (mean 3.50). NAs rated
      lowest their knowledge (3.42) and confidence (mean = 3.47) in their ability to
      decrease residents' agitation and aggressiveness once they become agitated or
      aggressive. CONCLUSIONS: These findings provide useful information that supports
      the need for violence prevention education and for developing violence prevention
      programs in nursing homes.

PMID- 12807603
TI  - A comparison of previous antibiotic therapy following isolation of MRSA versus
      MSSA in nursing home residents: a preliminary investigation.
AB  - OBJECTIVE: Antibiotic exposure is a risk factor for isolation of methicillin
      resistant Staphylococcus aureus (MRSA). We reasoned that this relationship might
      be especially strong if the comparison was targeted to antibiotics with activity
      against methicillin-sensitive Staphylococcus aureus (MSSA), but not MRSA.
      SUBJECTS: Forty-eight cases with initial MRSA clinical isolates (15 urinary, 19
      wound, 11 sputum, 3 blood) were matched to 48 with MSSA clinical isolates from
      the same location. In addition, 10 whose MRSA was noted screening around an index
      case were matched to 10 with negative screening cultures sampled around the same
      index case. DESIGN: MSSA was always/usually sensitive to dicloxacillin,
      amoxicillin/clavulanate, cephalosporins, imipenem, quinolones, and erythromycin,
      whereas MRSA was always/usually resistant. These antibiotics were defined as
      "targeted" and would be expected to facilitate the proliferation of MRSA by
      suppressing competing bacteria. We compared the use of all antibiotics over 60
      days in cases and controls. RESULTS: The comparison of antibiotic exposure in the
      48 clinical isolates revealed that 29 (60%) with MRSA isolates versus 16 (33%)
      with MSSA isolates had received a targeted antibiotic (RR 1.81, CI 1.33-3.34, P =
      0.006). Twelve (25%) with MRSA clinical isolates versus 3 with MSSA isolates (6%)
      had received a nontargeted antibiotic (RR 4.00, CI 2.10-14.18, P = 0.009). The
      comparison of antibiotic exposure in MRSA screening isolates versus negative
      controls revealed that 7 (70%) had received a targeted antibiotic versus 2 (20%)
      of controls (RR 3.50, CI 1.57-16.85, P = 0.009)). One in the screening group
      versus 2 controls had received a nontargeted antibiotic. Twenty-one (62%) of 34
      with MRSA (urine or wound) isolates versus 4 MSSA controls (12%) had received a
      quinolone (RR 5.25, CI 1.80-15.30, P < 0.000). CONCLUSION: There was a
      significant association between antibiotic exposure and MRSA isolates. The
      association was especially strong for quinolones with urinary or wound isolation
      of MRSA. Our data do not support the hypothesis that targeted antibiotic use was
      more likely to be associated with MRSA isolation than nontargeted antibiotic use.
      The use of nontargeted antibiotics was low, with greater use in the MRSA clinical
      group.

PMID- 12807606
TI  - Dehydration in frail, older residents in long-term care facilities.

PMID- 12807607
TI  - Evaluation of a nonintrusive monitor to reduce falls in nursing home patients.
AB  - OBJECTIVE: A clinical study was conducted to measure the effectiveness and
      operational characteristics of a new device intended to reduce the incidence of
      falls in elderly patients at high risk of falling. The NOC.watch device consists
      of a credit-card size device contained within an adhesive "patch"worn on the
      thigh continuously for many days. The patch is small, wireless, disposable,
      waterproof, shockproof, and unobtrusive. When a patient's leg becomes weight
      bearing (such as when a patient gets out of bed or stands up unassisted), the
      receiver emits an audible signal which both alerts the patient to sit down and
      also summons a caregiver. DESIGN: A crossover design was used to compare the fall
      rate of patients while wearing the NOC.watch device with the fall rate while not
      wearing it. Patients (n = 47) wore the device for one week, and were monitored
      for fall activity before, during, and after this week. The three time periods
      were referred to as the "Pre," "During," and "Post" periods, respectively.
      PARTICIPANTS: The study was conducted between November 1, 2000, and April 1,
      2001, in the Medicare unit of a skilled nursing facility in northern California.
      Forty-seven patients admitted to the unit with a fall risk assessment (FRA) score
      of at least 6 were entered into the study, with a mean FRA of 11.4. MEASUREMENTS:
      The main outcome measure was fall rate per 100 patient days. Qualitative
      observations of adverse effects on skin integrity, degree of staff and patient
      acceptance of the system, and lack of false alarms are also reported. Poisson
      regression with generalized estimating equations was used for analysis of fall
      rates. RESULTS: Forty-seven patients wore the device. Total number of patient
      days of observation were 273, 299, and 497 in the Pre, During, and Post periods,
      respectively, for a total of 1,069 days of observation. These patients had 11
      falls in the Pre period (4.0 falls per 100 days), 1 fall in the During period
      (0.3 falls per 100 days) and 17 falls in the Post period (3.4 falls per 100
      days). This 91% reduction in fall rate while wearing the NOC.watch is
      statistically significant with P = 0.02. False alarms were qualitatively reported
      to be low or nonexistent, and patient and caregiver acceptance of the device was
      reported to be high. No adverse effects on skin integrity were noted. Cognitively
      impaired patients, who have difficulty remembering to call for assistance,
      appeared to respond particularly well to the device alarm. CONCLUSIONS: The
      prototype NOC.watch device appears to have a large impact on reducing fall risk
      in nursing home patients, with minimal adverse effects. However, due to the lack
      of an equivalent control group, these results should be confirmed with a larger,
      randomized, controlled study to better estimate the true magnitude of the effect
      of the NOC.watch device on fall rates.

PMID- 12807609
TI  - Dehydration despite drinking: beyond the BUN/creatinine ratio.

PMID- 12807608
TI  - Case report: A giant leg abscess in a patient with dementia.

PMID- 12807610
TI  - Ethics corner: cases from the Hebrew Rehabilitation Center for Aged--sex in the
      facility.

PMID- 12807612
TI  - Issues involving sexual abuse of nursing facility residents.

PMID- 12807613
TI  - Health care coalition-building.

PMID- 12807614
TI  - Can goal-based advance planning guide medical care in the nursing home?
AB  - OBJECTIVE: To determine whether a goal-based system of advance planning, which
      allows patients to choose among five "pathways of care" (longevous,
      ameliorative/comprehensive, ameliorative/basic, palliative/comfort, or
      palliative/hospice), enables physicians to select treatment options in specified
      clinical situations. DESIGN: A pencil and paper test was administered in which
      clinicians were presented five common clinical scenarios and were asked which of
      four possible treatment options they would recommend, given a predetermined
      "pathway of care." SETTING: A 725-bed teaching nursing home and affiliated
      continuing care retirement community. MEASUREMENTS: The proportion of correct
      answers was measured for each clinician, for each clinical scenario, and for each
      pathway. RESULTS: Of the test answers, 78% coincided with the reference answers.
      The greatest rate of correct answers was found for the ameliorative/comprehensive
      pathway and the palliative/hospice pathway. CONCLUSION: Establishing pathways of
      care by asking nursing home residents to prioritize their goals of care may help
      clinicians narrow the range of appropriate options when facing an acute medical
      problem. Key Words: Advance planning; goals of care; treatment limitations

PMID- 12807615
TI  - Mental health training for nursing home staff using computer-based interactive
      video: a 6-month randomized trial.
AB  - OBJECTIVE: Mental health education for the staffs of nursing homes is difficult
      to provide and often inadequate. The objectives of this study were to design and
      assess a curriculum of staff training on depression and dementia that is
      accessible, educational, and relevant. DESIGN: A core curriculum of 12 computer
      based interactive video training modules was created in a television news
      documentary format to educate nursing home staffs. A randomized trial of the
      first six modules, which are dedicated to mental health and aging, was conducted
      at a computer site (CS), a "lecture site" (LS), and control site (CON). SETTING:
      Three not-for-profit nursing facilities in Western Pennsylvania. PARTICIPANTS:
      The certified nursing assistants, and other nursing staff participated in the
      study as part of their required training. INTERVENTION: Nursing staffs at the two
      intervention sites (CS and LS) were mandated to participate in monthly
      educational sessions. At the CS, the computer program scheduled staff members
      each month for 45 minutes of individual, self-paced training using the
      interactive video modules. At the LS, staff members were scheduled to attend a 45
      minute monthly lecture with identical learning objectives delivered by an
      advanced degree nurse educator. A videotape of the lectures was shown at two
      additionally scheduled times during the month to accommodate all shifts.
      MEASUREMENTS: Compliance and satisfaction with training were monitored at both
      intervention sites. Knowledge was assessed at the CS, LS, and CON, before each
      monthly training session, and with a cumulative post-training exam, administered
      at the end of the 6-month study. RESULTS: Over the 6-month period, training
      compliance was 66% and 22% at CS and LS, respectively (P < 0.001). Satisfaction
      with training and the relevance of training were rated significantly higher at
      the CS (P < 0.0001). Before the study, assessed knowledge was similar at the CS,
      LS, and CON. After 6 months, the CS scored significantly higher than the LS and
      CON in terms of knowledge (P < 0.005). CONCLUSION: Individual, self-paced,
      interactive video education for nursing home staff resulted in greater compliance
      and satisfaction with training compared to staff receiving lectures. Knowledge of
      core concepts was greater for staff of the computer site compared to the staffs
      of either the lecture or control sites at the end of this 6-month study.

PMID- 12807616
TI  - Demographic and health characteristics of residents choosing to use on-site
      medical care in a newly opened continuing care retirement community (CCRC).
AB  - OBJECTIVE: To determine demographic and health characteristics of older adults
      choosing to use on-site medical care in a continuing care retirement community
      (CCRC). DESIGN: A descriptive study of residents moving into a newly opened CCRC.
      Residents responded to a self-report mail survey composed of questions related to
      reasons for moving to a CCRC, health and functional status,health care use during
      the previous 5 years. RESULTS: Of 942 residents, 642 (68%) completed the survey.
      Medical center users and nonusers were similar demographically and reported
      similar reasons for moving to the CCRC including desire for a low maintenance
      apartment (49% vs. 48%; P = 0.806), concern about health or spouse's health (67%
      vs. 63%; P = 0.345), and desire for social activities (63% vs. 58%; P = 0.151).
      However, on-site medical center users versus nonusers reported increased rates of
      fair/poor health (31% vs. 18%; P = 0.0001), fair/poor vision (27% vs. 15%; P =
      0.0003),difficulty walking in the home (13% vs. 8%; P = 0.53), using the toilet
      (6% vs. 2%; P = 0.044), shopping (29% vs. 20%; P = 0.007), using transportation
      (19% vs. 10%; P = 0.005), doing laundry (13% vs. 7%; P = 0.016), using the
      telephone (8% vs. 3%; P = 0.002), and taking medication (5% vs. 1%; P = 0.022).
      CONCLUSION: For both users and nonusers of the medical center, the most
      frequently cited reason for moving to the CCRC was concern about health. On-site
      medical center users had lower perceived health, were functionally more disabled,
      and had health characteristics that made them at higher risk for high health care
      utilization. The challenges to provide high quality medical care and enhance
      quality of life for CCRC residents will continue to increase. Physicians should
      play an active role not only in providing medical care to CCRC residents, but
      also in providing medical leadership for these institutions.

PMID- 12807617
TI  - Common and gender specific factors associated with one-year mortality in nursing
      home residents.
AB  - OBJECTIVES: To identify common and gender-specific factors associated with
      mortality in two distinct nursing home (NH) populations: newly admitted (NA), and
      long-stay (LS) residents. DESIGN: A retrospective cohort study. SETTING: NH
      facilities in the state of New York. PARTICIPANTS: A total of 59,080 NA female
      and 28,080 NA male NH residents, and 24,260 LS female and 8,928 LS male NH
      residents evaluated between June 1994 and December 1997 who were at least 65
      years of age. MEASUREMENTS: Minimum Data Set information including measures of
      health, functional, cognitive, psychological, and social status. RESULTS:
      Multivariate proportional hazards regression results indicate that in NA
      residents, use of feeding tubes, bowel incontinence, and refuses fluids were
      associated with mortality in women only, whereas fever was associated with
      mortality in men only. Cancer and congestive heart failure (CHF) were more
      strongly associated with mortality in women than men. In LS residents,
      deterioration in communication, refuses fluids, use of indwelling catheters, and
      deterioration in cognition were associated with mortality in women but not men.
      Bedfast most of the time, use of new medications, and a balance problem were
      associated with mortality in men but not women. Shortness-of-breath was more
      strongly associated with mortality in women than men. CONCLUSIONS: In both NA and
      LS residents, although men and women share many common factors associated with
      mortality, each gender has some unique factors associated with mortality.
      Furthermore, the strength of some common factors is significantly different
      across genders. These readily available data could be useful in making medical
      decisions and advance directive planning, and in the development of quality
      improvement initiatives and mortality prediction models.

PMID- 12807618
TI  - Clinical characteristics of nursing home residents hospitalized with heart
      failure.
AB  - OBJECTIVE: The purpose of this retrospective study was to describe the clinical
      characteristics of heart failure among nursing home residents hospitalized with
      heart failure and determine the validity of dyspnea at rest in the diagnosis of
      heart failure. METHODS: Subjects were nursing home residents hospitalized with a
      diagnosis of heart failure. Data on demographic and various admission
      characteristics were collected by chart abstraction. Proportions of patients
      presenting with various symptoms and signs of heart failure have been described.
      The diagnosis of heart failure was confirmed using modified Framingham criteria.
      The sensitivity, specificity, and positive predictive value of the symptom of
      dyspnea at rest in the diagnosis of heart failure in nursing home residents
      hospitalized with heart failure were then estimated. RESULTS: Patients (N = 98)
      were elderly, predominantly female and about one-fifth African-American. Dyspnea
      at rest was the presenting symptom of 85 (87%) patients. Sixty-eight (69%)
      patients met modified Framingham criteria for the diagnosis of heart failure.
      Dyspnea at rest had a sensitivity of 91%, specificity of 23%, and predictive
      value positive of 73% for diagnosis of heart failure. CONCLUSION: Dyspnea at rest
      was the most common symptom among this cohort of nursing home residents
      hospitalized with heart failure and has a potential to play a useful role in the
      diagnosis of heart failure in these patients.

PMID- 12807619
TI  - Psychiatric consultation: when to request it and what is the role of the
      consultant.

PMID- 12807620
TI  - Pulmonary vest therapy in pediatric long-term care.
AB  - OBJECTIVES: Pulmonary infections are common in children with quadriplegic
      cerebral palsy. High frequency chest wall oscillation with the vest therapy (VT)
      is used to promote pulmonary clearance and to prevent pneumonias in cystic
      fibrosis patients. The purpose of this study was to ascertain the effectiveness
      of VT in patients with quadriplegic cerebral palsy who reside in pediatric
      skilled nursing facilities. METHODS: Seven individuals with quadriplegic cerebral
      palsy, who had frequent pulmonary infections were identified (age range: 7-28
      years; median 19 years; 2 females and 5 males). Five had a tracheostomy and three
      an active seizure disorder. Clinical data was collected for 12 months before
      starting VT and during 12 months of VT. RESULTS: The total number of pneumonias
      that required antibiotics decreased from 36 per year before VT, to 18 during the
      year of VT (P < 0.05). The number of hospitalizations due to pneumonia decreased
      from 9 to 3. With VT, the frequency of effective suctioning of pulmonary
      secretions was significantly increased (P < 0.01). In the patients with epilepsy,
      with VT, the average monthly frequency of seizures decreased from 4 to 1, from 9
      to 2, and from 9 to 1. CONCLUSION: VT resulted in more effective suctioning of
      pulmonary secretions, reduced incidence of pneumonia, and reduced number of
      hospitalizations for pneumonia. In patients with epilepsy, VT resulted in reduced
      seizure frequency. VT was tolerated well, without complications or side effects.
      Further clinical investigations of the use of VT in cerebral palsy are indicated.

PMID- 12807621
TI  - Unusual weakness in nursing home residents--don't forget myasthenia gravis.

PMID- 12807622
TI  - Ethics corner: cases from the Hebrew Rehabilitation Center for Aged--restraint
      complaint.

PMID- 12807624
TI  - The United Kingdom National Service Framework for Older People--one year on.

PMID- 12807625
TI  - A dietitian's experience working in a Jewish long-term care facility.

PMID- 12807626
TI  - Osteoporosis in the elderly: a clinical perspective of current and future
      therapies.

PMID- 12807627
TI  - New approaches to treatment of dementia: optimizing resident function and
      caregiver efficiency.

PMID- 12807628
TI  - Cost-effective therapies in nursing home patients with epilepsy and seizures.

PMID- 12807629
TI  - Anticoagulation in long-term care: the state of the art.

PMID- 12807630
TI  - Quality care: a practical guide to managing behavioral symptoms of dementia.

PMID- 12807631
TI  - Contemporary issues in the diagnosis and treatment of late-life depression.

PMID- 12807632
TI  - Regulatory and legal barriers to effective pain management in the long-term care
      setting.

PMID- 12807633
TI  - Pharmacotherapy for the older patient with psychosis.

PMID- 12807634
TI  - Facility investigations: medical directors should know the rules.

PMID- 12807635
TI  - MDS quality indicators: looking beneath the numbers.

PMID- 12807636
TI  - House calls well worth a visit.

PMID- 12807638
TI  - Calls for unity in revamping the survey and enforcement system.

PMID- 12807637
TI  - AMDA House of Delegates addresses surveys, staffing, and public image of nursing
      facilities.

PMID- 12807639
TI  - Collective approach facilitates interactions at an Alzheimer's facility.

PMID- 12807640
TI  - The medical director's role in culture change.

PMID- 12807641
TI  - Time and economic cost of constipation care in nursing homes.
AB  - OBJECTIVE: Chronic constipation is a common disorder among residents in long-term
      care; yet the cost to the nursing home of constipation-related care is not known.
      The objective of this study was to quantify the nursing staff and supply-related
      cost of constipation care to nursing homes from the perspective of the nursing
      home. DESIGN: Prospective, observational time-and-motion design. SETTING: Two
      United States nursing homes. PARTICIPANTS: A total of 59 nursing home residents
      with chronic constipation and nursing staff providing constipation care to them.
      MEASUREMENTS: Actual time to complete constipation care-related tasks was
      measured via stopwatch by trained observers, and the number and professional
      level (eg, staff nurse, CNA) of staff performing each task was recorded.
      Frequency of constipation care task data was obtained through 60-day
      retrospective medical chart review for each subject. Nurse wage rate data was
      obtained from the Nursing Home Salary and Benefits Report, a US-based national
      source. Resident and nursing home descriptive information was also collected.
      RESULTS: The average cost per task occurrence ranged from 0.72 US dollars for
      enema administration to 1.74 US dollars for oral medication administration.
      Average nursing staff costs per subject per year were 1577 US dollars for oral
      medication administration, 215 US dollars for dietary supplement administration,
      39 US dollars for constipation assessment, 17 US dollars for suppository
      administration, and 6 US dollars for enema administration. Based on estimates of
      frequency of occurrence, the total annual labor and supply cost per long-term
      care resident with constipation was 2253 US dollars. CONCLUSION: Nursing staff
      performance of constipation care-related tasks is time consuming and costly in
      the long-term care setting.

PMID- 12807642
TI  - The cost of chronic constipation.
AB  - OBJECTIVES: This study investigates the cost of chronic constipation care. DESIGN
      AND PARTICIPANTS: A consecutive sample of 31 chronically constipated elderly
      patients. SETTING: A not-for-profit long-term care facility in New Hyde Park, New
      York. MEASUREMENTS: Patient demographics and functional status, including
      activity of daily living scores, diagnosis, and medications were recorded. All
      constipation medication costs were obtained using the average wholesale price
      obtained from the Redbook (November 1999). All subjects were closely monitored
      for constipation care during two shifts a day (from 7:00 AM to 11:00 PM), over a
      6-week period resulting in the collection of 1,860 shift reports. Each component
      of constipation treatment cost, namely drugs and staff time for drug
      administration, was identified and analyzed. RESULTS: The average number of
      nursing interactions for constipation treatment was 23.3 per month. The average
      cost per day for care specifically for the treatment of constipation was 2.11 US
      dollars. Fleet Enema trade mark and milk of magnesia accounted for 49% of all
      treatments. Administration (staffing) costs accounted for 70% of total drug
      costs. CONCLUSIONS: Although laxatives are the most frequently prescribed drugs
      used in long-term care settings, drug utilization patterns and associated costs
      in the treatment of chronic constipation have not been systematically reported.
      Our study identified staffing as the major cost factor in constipation care.

PMID- 12807643
TI  - Incidence and costs of acute medical conditions in long-stay incontinent nursing
      home residents.
AB  - OBJECTIVES: To determine the incidence of acute medical conditions in incontinent
      nursing home residents, and associated costs of diagnostic testing and treatment
      DESIGN: Prospective, cohort study. SETTING: Three community nursing homes.
      PARTICIPANTS: 161 long-stay residents with urinary incontinence in (mean age 86
      years, 77% female, 92% white). MEASUREMENTS: Acute medical conditions were
      identified prospectively through medical record review based on standardized
      criteria. All diagnostic testing and treatment provided for these conditions were
      recorded, and related costs in the nursing home were assigned based on 1997-1998
      Medicare and Medicaid reimbursement. RESULTS: The highest incidences of illness
      were for dermatological conditions (107 episodes per 1000 patient-weeks,
      involving 70% of subjects), respiratory illnesses (29 per 1000 patient-weeks, 47%
      of subjects) and gastrointestinal illnesses (24 per 1000 patient-weeks, 36% of
      subjects). Among episodes with an incidence of at least 5 per 1000 patient-weeks,
      the illness events with the highest median diagnostic testing and treatment costs
      per episode were pneumonia, acute bronchitis, and depression. Only 42 out of the
      total 1071 episodes identified resulted in a hospitalization. Significant
      predictors of higher illness incidence included greater baseline comorbidity and
      higher number of routine medications (model adjusted R-square = 0.319, P =
      0.021). CONCLUSION: Acute illness is very common among incontinent nursing home
      residents, and is generally diagnosed and treated at the nursing home site, with
      variation among conditions in associated costs. Important policy implications
      include resource allocation (including appropriate staffing patterns),
      educational and quality improvement activities, and future research and guideline
      development for the optimal management of medical conditions in the nursing home
      setting.

PMID- 12807644
TI  - Use of antihypertensive drug therapy in older persons in an academic nursing
      home.
AB  - OBJECTIVES: To determine the prevalence of hypertension and the appropriate
      treatment of hypertension in older persons in an academic nursing home. DESIGN:
      The charts of all persons aged > or = 59 years currently residing in a nursing
      home affiliated with Westchester Medical Center/New York Medical College were
      analyzed by two geriatrics fellows according to a protocol designed by one of the
      authors (W.S.A.). SETTING: An academic nursing home affiliated with Westchester
      Medical Center/New York Medical College. PARTICIPANTS: The study population
      included 96 men and 159 women, mean age 77 +/- 9 years (range, 59-100 years).
      RESULTS: Hypertension was present in 129 of 255 persons (51%). Clinical
      cardiovascular disease or target organ damage or diabetes mellitus was present in
      121 of 129 persons (94%) with hypertension. Hypertension was poorly controlled in
      21 of 129 persons (16%). Of 129 persons with hypertension, 70 (54%) were treated
      with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1
      receptor blockers, 61 persons (47%) with beta blockers, 43 persons (33%) with
      diuretics, 36 persons (28%) with calcium channel blockers, 5 persons (4%) with
      alpha blockers, and 5 persons (4%) with other antihypertensive drugs. Of 54
      persons with hypertension and diabetes mellitus, 37 persons (69%) were treated
      with ACE inhibitors or angiotensin II type 1 receptor blockers. Of 58 persons
      with hypertension and coronary artery disease, 33 persons (57%) were treated with
      ACE inhibitors or angiotensin II type 1 receptor blockers, 31 persons (53%) with
      beta blockers, 20 persons (34%) with diuretics, 18 persons (31%) with calcium
      channel blockers, 2 persons (4%) with alpha blockers, and 4 persons (7%) with
      other antihypertensive drugs. Of 31 persons with hypertension and heart failure,
      only 5 persons (16%) had measurement of left ventricular ejection fraction. Of 31
      persons with hypertension and heart failure, 30 persons (97%) were treated with
      diuretics, 21 persons (68%) with ACE inhibitors or angiotensin II type 1 receptor
      blockers, 18 persons (58%) with beta blockers, and 8 persons (26%) with calcium
      channel blockers. CONCLUSIONS: Of older persons with hypertension in an academic
      nursing home, 16% had poor control of their hypertension. There was overuse of
      calcium channel blockers and alpha blockers and underuse of diuretics, beta
      blockers, and ACE inhibitors in treating hypertension. Physician education needs
      to be intensified to provide better medical care of older persons with
      hypertension through the use of optimal doses of drugs found to be effective and
      safe by evidence-based studies.

PMID- 12807645
TI  - Impact of physician telephone management of nursing home residents before the
      initial assessment: a pilot study.
AB  - OBJECTIVE: To describe physician telephone management of newly admitted nursing
      home residents before direct evaluation by the physician, and the effect on
      resident outcomes. DESIGN: Retrospective chart review of 111 consecutive
      discharge records from two proprietary community nursing homes in Baltimore,
      Maryland in 1999. MEASUREMENTS: Data regarding the admission process were
      collected, with an emphasis on physician telephone orders at admission and all
      subsequent telephone orders before the first physician visit. Physicians were
      categorized as attending physicians or on-call physicians. Unexpected outcomes
      defined as an unplanned admission to an acute hospital or an unanticipated death
      within 14 days of admission to the nursing home were identified. The
      relationships among resident, physician, and admission characteristics and
      unexpected outcomes were analyzed. RESULTS: Most residents (97 of 111 (87%)) were
      admitted from an acute hospital, and the remaining 13% were admitted from home or
      another nursing home. An attending physician confirmed admission orders for 87 of
      111 (78%) residents, and an on-call physician confirmed admission orders for the
      remainder. Physicians changed medications at the time of admission, as compared
      with preadmission medications, in 58 of 111 (52%) residents and ordered
      laboratory studies or radiographs in 59 of 111 (53%). On-call physicians were
      just as likely to make both types of changes as attending physicians. In the time
      interval after the initial telephone contact but before the first physician
      visit, medication changes were made in 35 of 111 (32%) residents and testing was
      ordered in 16 of 111 (14%). Nineteen of 111 (17%) residents were either
      readmitted to the hospital or died within 14 days of admission to the nursing
      home. These unexpected outcomes were statistically less likely to occur in the
      group of residents for whom physicians made medication changes at the time of
      admission as compared to the group for whom no medication changes were made [6 of
      58 (10%) versus 13 of 53 (25%), P = 0.04, respectively], and in the group for
      whom tests were ordered at the time of admission as compared to not ordered [4 of
      59 (7%) versus 15 of 51 (29%), P = 0.002, respectively]. There were no
      differences in the likelihood of unexpected outcomes when physicians made
      medication changes or ordered tests after the time of admission but before the
      first physician visit. CONCLUSIONS: In this study, physicians made adjustments in
      medications and ordered tests for newly admitted nursing home patients before
      seeing the resident in the majority of cases. Unexpected outcomes including
      readmission to the hospital or death within 14 days of admission were less common
      among those residents when such changes were made at the time of admission.
      Further studies are needed to identify those changes as well as those resident
      and physician characteristics that might lead to improved outcomes.

PMID- 12807646
TI  - Cooperation in the care of the institutionalized elderly in a rural community.
AB  - OBJECTIVE: To develop a method of addressing and minimizing the institutional,
      cultural, and regulatory barriers to the care of nursing facility residents in
      our community. METHODS: Nurses, administrators, and medical directors from all
      the nursing facilities in our community plus representatives from the community
      hospital participated in a monthly meeting where difficult issues in the care of
      nursing facility residents were discussed. The committee developed responses to
      these issues that were implemented throughout the community. RESULTS: This
      committee has provided an opportunity for the whole community to address problems
      in the care of the institutionalized elderly. Systems have been developed which
      have improved communication between nurses and physicians and between nursing
      facilities and the hospital. Community standards for the care of common problems
      in nursing facility residents have also been developed. Other unexpected benefits
      have included community discussion of regulatory concerns, nurse assistant
      education, and care at the end of life, as well as coordination of laboratory
      services in the nursing facilities. Other rural communities may find a similar
      approach useful.

PMID- 12807647
TI  - Responsibilities of attending physicians in long-term care facilities.

PMID- 12807648
TI  - Ethics corner: cases from the Hebrew Rehabilitation Center for Aged--problematic
      proxies.

PMID- 12807650
TI  - Quality improvement case study: issues involving a nursing facility's obligation
      to follow its own policies.

PMID- 12807651
TI  - Commentary on the quality improvement case study.

PMID- 12807652
TI  - The Ombudsman Program: an overview of the history, purpose, and role of ombudsmen
      in long-term care facilities.

PMID- 12807653
TI  - Bert's Dad.

PMID- 12807654
TI  - Long-term care experience in an internal medicine residency program.
AB  - OBJECTIVES: To assess the impact of long- term care experience on internal
      medicine residents through prequestionnaires and postquestionnaires. DESIGN: A
      prospective study conducted from February 1999 to March 2000. SETTING: "Daughters
      of Israel," a 300-bed, long-term care institution in West Orange, New Jersey.
      PARTICIPANTS: Twenty-five 3rd-year medical residents (PGY3) from Saint Barnabas
      Medical Center, Livingston, and Newark Beth Israel Medical Center, Newark, New
      Jersey, who each rotated in a long-term care setting. INTERVENTION: Medical
      residents completed validated questionnaires before and after their rotation.
      MEASUREMENTS: The questionnaire integrated three subcategories: self-reported
      skills, knowledge, and attitudes. RESULTS: Self-reported skills in performing:
      (a) Histories and physicals increased from mean of 3.65 to 4.48 (1 = low; 5 =
      high). P < 0.0005; (b) Functional assessment from mean of 3.47 to 4.53, P <
      0.0005; and (c) Advance directive discussion from 3.78 to 4.37, P < 0.0005. All
      self-reported measures of knowledge in geriatrics increased significantly. All
      self-reported measures of attitudes toward the elderly also improved
      significantly. Career choice of geriatrics was not significantly altered by this
      experience. CONCLUSIONS: There was improvement in self-reported skills,
      knowledge, and attitudes for medical residents completing a rotation in the
      nursing home. These conclusions were based on validated questionnaires and
      prospective data. Our results support recommendations by the American Medical
      Directors Association (AMDA)the American Geriatric Society (AGS) to include the
      long-term care setting as a site for the geriatric education of medical
      residents.

PMID- 12807655
TI  - Hospitalization risk following admission to an academic nursing home.
AB  - OBJECTIVES: Nursing home residents are at risk for experiencing acute illness and
      hospitalization early in nursing home stay. The objectives of this study were (1)
      to measure the probability of hospitalization over time from nursing home
      admission, and (2) to determine resident risk factors for early hospitalization.
      DESIGN: Prospective observational study. SETTING: 409-bed urban, not-for-profit
      academic nursing home. PARTICIPANTS: 204 consecutive newly admitted residents who
      did not previously reside in the nursing home. MEASUREMENTS: Demographic profile,
      chronic comorbidity, physical function, recent medical events, admission
      condition and anticipated length of stay were ascertained on admission to the
      nursing home. Hospitalization and acute illness were recorded each week after
      nursing home admission. Data were collected primarily by chart review except for
      acute illness, which was identified by nurse report and chart review according to
      previously established criteria. RESULTS: Subjects were 69% female and 62% white.
      The mean age was 83. The percentage of residents experiencing their first
      hospitalization peaked 2 and 7 weeks after nursing home admission and after 14
      weeks plateaued at a low rate. The percentage with acute illness (commonly
      gastroenteritis, urinary tract infection, and pneumonia) paralleled that of
      hospitalization. In multivariate proportional hazards analysis, resident factors
      independently associated with early first hospitalization were atrial
      fibrillation (21% of subjects, 2.6 risk ratio), history of stroke (26%, 2.5),
      history of depression (25%, 1.9), absence of dementia (62%, 2.3), and receiving
      antibiotics on admission (23%, 3.3). Residents with 0, 1, 2,> or = 3 of these
      characteristics had 9%, 19%, 34% and 62% probability, respectively, of being
      hospitalized in the first 8 weeks of nursing home stay. CONCLUSIONS: In a large,
      urban, academic nursing home, residents' risk of hospitalization varied over time
      from admission and among different subgroups of residents. These results can be
      used to develop interventions to prevent acute illness and hospitalization early
      in nursing home stay and to enhance the communication of prognostic risk to
      nursing home residents, their caregivers and medical providers.

PMID- 12807656
TI  - Cerumen, hearing, and cognition in the elderly.
AB  - OBJECTIVE: This investigation was performed to study the prevalence of cerumen
      impaction and evaluate its impact on hearing and cognition in elderly patients
      admitted to a skilled nursing facility (SNF). DESIGN: Prospective clinical trial
      using a pretest-posttest design. SETTING: A 160-bed skilled nursing facility.
      SUBJECTS: Twenty-nine English-speaking residents over the age of 65 who were new
      admissions to a SNF. INTERVENTION: Participants with cerumen that occluded 50% or
      more of the external auditory canal had cerumen removed with a cerumenolytic
      agent and tepid water irrigation. MEASUREMENTS: A standardized Folstein Mini
      Mental Status Exam (MMSE)(1) and audiometric evaluation were administered to all
      participants before and after cerumen removal. Participants who did not have
      cerumen impaction served as controls. Hearing changes were scored as "+1" for an
      improvement, "0" for no change and "-1" for a loss at each frequency tested.
      Results were compared using 2-tailed paired t tests. RESULTS: Nineteen
      participants (65.5%) had cerumen in at least one ear. Following cerumen removal,
      hearing improved in 80% of impacted ears compared with 3% of nonimpacted ears (P
      < 0.001). The average change in hearing score following cerumen removal was 0.26
      +/- 0.50 compared with an average change of 0 +/- 0.16 in the controls (P <
      0.001). The average change in MMSE score was 1.05 +/- 1.6 for participants who
      had cerumen removed compared with -0.30 +/- 0.95 for the controls (P < 0.01).
      CONCLUSIONS: This study found a majority of residents admitted to the SNF had
      cerumen impaction. Evaluation of hearing and mental status following removal of
      cerumen resulted in a statistically significant improvement in hearing and
      cognition when compared with controls. Removal of cerumen is a relatively safe
      and easy procedure that can be done at minimal cost and provide a significant
      benefit to residents of a SNF.

PMID- 12807657
TI  - Accuracy of minimum data set in identifying residents at risk for undernutrition:
      oral intake and food complaints.
AB  - OBJECTIVE: to evaluate the accuracy of nursing home (NH) staff in documenting two
      Minimum Data Set (MDS) items that are used to identify residents at risk for
      undernutrition, low oral intake and food complaints, using standardized
      observation and interview assessment protocols implemented by research staff.
      DESIGN AND METHODS: MDS information related to low oral intake (item K4c: <75% of
      most meals) and complaints about the taste of food (item K4a) was compared to
      independent evaluations of low oral intake and food complaints for a random
      sample of 75 residents in two proprietary NHs within the same month that a
      complete MDS assessment was due for each participant. Direct observations were
      conducted by research staff during nine mealtime periods for 3 consecutive days
      according to a standardized mealtime observational protocol to estimate low oral
      intake; and, two one-on-one interviews with residents were conducted on two
      consecutive days using standardized questions to assess the stability of food
      complaints. RESULTS: Research staff documentation based on direct observation and
      resident interviews showed a significantly larger number of residents being
      identified as potentially at risk for undernutrition due to low oral intake (73%)
      and/or stable complaints about the taste of food (32%) as compared with NH staff
      documentation of MDS items K4c (44%) and K4a (0%), respectively, within the same
      month. A total of 47% of the participants expressed stable complaints about some
      aspect of the NH food service (eg, variety, appearance, temperature). CONCLUSION:
      The documentation of low oral intake and food complaints on the MDS was
      inaccurate and resulted in a significant underestimate of residents with either
      of these risk factors for undernutrition.

PMID- 12807658
TI  - Characterizing behavioral and psychological symptoms of dementia (BPSD) among
      geropsychiatric inpatients.
AB  - OBJECTIVE: The purpose of this database analysis was to determine if, upon
      hospital admission, particular behavioral and psychological symptoms of dementia
      (BPSD) could be linked to patient characteristics, levels of cognitive or
      clinical functioning, and/or type of residence before hospitalization. METHODS:
      Sampled were geropsychiatric inpatients with a primary DSM-IV discharge diagnosis
      of dementia, who participated in the Mental Health Outcomes, Inc. CQI+(SM)
      measurement program between January 1, 1996 and December 31, 1999 and who had
      admission data on all study variables and dementia subtype diagnosis at discharge
      (N = 2256). BPSD clusters were derived from the 16 behavioral items of the
      Psychogeriatric Dependency Rating Scale (PGDRS). Subgroups were formed on (1)
      level of cognitive impairment, (2) depressive symptoms, (3) independence of prior
      residence, (4) age, (5) gender, (6) race, (7) dementia subtype, and (8) prior
      psychiatric hospitalization. The relationship of these variables to presence of
      each PGDRS item was explored with Chi-Square Automatic Interaction Detection
      (CHAID). A random sample (75% of the patient sample) was used to create the
      model, with the remaining 25% used for cross-validation. Binary multiple logistic
      regression was employed to obtain odds ratios for variables significantly related
      (at < or = 0.01) to PGDRS items. RESULTS: The sample was 66% female, with an
      average age of 81. The regression analysis revealed that cognitive functioning
      was significantly associated with 12 of 16 PGDRS items. Odds ratios indicated a
      7% to 36% increase in odds of observing the target BPSD for a 3-point difference
      in MMSE. Also, living in a "dependent" environment (eg, nursing home) before
      hospitalization was significantly associated with 10 behaviors. Odds of
      displaying four (active aggression, disruptive behavior, noisy behavior, and
      verbal aggression) more than doubled for those admitted from a dependent living
      environment versus an independent one. Finally, age was related to only 1 PGDRS
      item (socially objectionable behavior). CONCLUSIONS: Findings help identify
      particular behaviors of dementia associated with being admitted to acute care
      from a restricted environment such as a nursing home. Treatments effectively
      targeting these BPSD may impact the intensity and costs of services required.

PMID- 12807659
TI  - Tardive dyskinesia in elderly patients: an update.
AB  - The use of antipsychotic agents can be limited by side effects, particularly
      extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). These neurologic
      movement disorders can occur early in the course of treatment (often as EPS) or
      as a more latent effect (TD). TD can be debilitating, and several patient-related
      and treatment-related factors have been associated with an increased risk for its
      development. Of these, older age has been strongly linked to TD. The advent of
      novel antipsychotics for the treatment of schizophrenia and severe behavioral
      disorders permits the use of such agents with reduced risk of EPS and TD. Most
      clinical trials of the novel antipsychotics have enrolled younger patients, but
      some data on their efficacy and safety in the elderly are now available. This
      article reviews the relationship between TD and aging and its treatment in
      elderly patients.

PMID- 12807660
TI  - Use and management of chronic urinary catheters in long-term care: much
      controversy, little consensus.
AB  - In long-term care facilities, 5 to 15% of residents have chronic urinary
      catheters in place. Catheters are commonly used for urinary retention,
      incontinence control, wound management, and patient comfort. The appropriate use
      and management of these devices continues to be studied and debated.
      Transurethral catheters are more common than suprapubic or condom-type devices,
      but no method has been proven superior for use in long-term care. Although some
      catheter management and infection control measures are well supported in the
      medical literature, clinical practices still vary widely. The accurate diagnosis
      of urinary tract infection can be especially challenging in this population. Many
      aspects of catheter care remain to be clarified, and further research based in
      chronic care settings is needed.

PMID- 12807661
TI  - The ADAPT Program at Geriatrix, Inc.
AB  - Behavioral problems in elderly patients are stressful for families, long- term
      care staff and health care providers. The individual patient's quality of life
      can suffer, and other residents may become fearful when behavioral problems are
      not appropriately addressed. Management of other issues becomes more difficult.
      Treatment approaches exist for behavioral problems, but at Geriatrix we found
      them difficult to apply. In response, we developed and tested our own approach to
      the behavioral problems of Agitation, Depression, Anxiety, Pain, and Thinking,
      the ADAPT Program. (This is not to be confused with ADAPT, the Alzheimer's
      Disease Anti-inflammatory Prevention Trial). The mission of our program is to
      identify and stratify those behavioral problems that are treatable and then to
      apply established guidelines for the management of these problems. This goal is
      accomplished using the tools of (a) word association and (b) probability
      weighting that involve the entire care team as well as family members.

PMID- 12807662
TI  - Clinical presentations in monozygotic twins with dementia with Lewy bodies.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) is widely recognized as the second
      most common neurodegenerative cause of dementia in patients over the age of 65.
      The clinical distinction between DLB and Alzheimers's disease (AD) can be
      difficult due to the significant clinical overlap between the two disorders.
      Although the specificity of current consensus criteria is high, the sensitivity
      of case detection is lower and more variable. In some cases, the diagnosis is
      only made at postmortem examination. CASE REPORT: Monozygotic twins with the
      neuropathological diagnosis of Lewy body disease are presented in this report.
      Despite a very similar presentation and a comparable course of illness, the twins
      received different clinical diagnoses during life, one DLB and the other AD. This
      highlights the difficulty of making a clinical diagnosis of DLB, which very much
      depends on recognizing the features of fluctuation in level of awareness,
      hallucinations, delusions and the occurrence of falls, and the interpretation of
      the importance of these signs and symptoms. Pathological examination was
      virtually identical for the two cases showing the classic neuropathological
      features of Lewy Body disease.

PMID- 12807663
TI  - The Vanderbilt Fall Prevention Program for long-term care: eight years of field
      experience with nursing home staff.

PMID- 12807664
TI  - Nutritional assessment and care of nursing facility residents: a practical
      approach.

PMID- 12807665
TI  - Ethics corner: cases from the Hebrew Rehabilitation Center for Aged.

PMID- 12807667
TI  - What's next?

PMID- 12807668
TI  - Who's going to cause me trouble? Predicting behavioral disturbances in demented
      patients.

PMID- 12807669
TI  - Morphological characterization of elastin-mimetic block copolymers utilizing cryo
      and cryoetch-HRSEM.
AB  - Elastin-mimetic block copolymers were produced by genetic engineering.
      Genetically driven synthesis permitted control of the final physiochemical
      characteristics of the block copolymers. We designed BB and BAB block copolymers
      in which the A-block was hydrophilic and the B-block was hydrophobic. By
      designing the copolymers in this manner, it was proposed that they would self
      assemble into micellar aggregates that, at high concentration, would form
      thermoreversible hydrogels. To analyze the three-dimensional fine surface
      morphology of the copolymers, to the resolution level of a few nanometers, we
      employed cryo-HRSEM. This method provided vast expanses of the specimen in its
      frozen hydrated state for survey. In our initial cryo-HRSEM studies, we observed
      the protein filaments and micelles surrounded by lakes of vitreous ice. Upon
      examination at low and intermediate magnifications, there was an extensive
      honeycomb-like filamentous network. To delineate the fine morphology of the
      hydrogel network at high magnification and to greater depths, we cryoetched away
      unbound water from the sample surface, in high vacuum, prior to chromium
      deposition. By using this technique, we were able to visualize for
      characterization purposes the fine fibril networks formed from the micellar
      aggregates over the surface of the hydrogel.

PMID- 12807670
TI  - Intraspinal endodermal cyst: ultrastructural study of abnormal cilia.
AB  - Abnormal cilia were demonstrated in the lining epithelial cells of three cases of
      intraspinal endodermal (bronchogenic) cyst. The changes comprised a wide spectrum
      of ultrastructural abnormalities, including (a). cilia with abnormal axonemal
      microtubules, (b). swollen cilia, (c). compound cilia with or without excessive
      ciliary matrix, (d). naked cilia without limiting membrane, and (e).
      intracytoplasmic cilia and aggregates of microtubules. Of these, compound cilia
      and swollen cilia were most common. Cilia with dynein arm deficiency were not
      observed. Ciliary abnormalities found in the present study were very similar to
      those described in the bronchial epithelium of various diseases. The present
      findings suggest that the lining epithelium of intraspinal endodermal cyst shares
      similar ciliogenesis and susceptibility to abnormal ciliary formation as that of
      the bronchial epithelium.

PMID- 12807672
TI  - Compositional averaging of backscatter intensities in compounds.
AB  - We present high-precision measurements of pure element stable isotope pairs that
      demonstrate mass has no influence on the backscattering of electrons at typical
      electron microprobe energies. The traditional prediction of average backscatter
      intensities in compounds was pragmatically based on elemental mass fractions. Our
      isotopic measurements establish that this approximation has no physical basis. We
      propose an alternative model to mass fraction averaging, based on the number of
      electrons or protons, termed "electron fraction," which predicts backscatter
      yield better than mass fraction averaging. We also present an improved
      backscatter (electron loss) factor based on a modified electron fraction average
      for the ZAF atomic number correction that provides a significant analytical
      improvement, especially where large atomic number corrections are required.

PMID- 12807671
TI  - Imaging mitochondrial organization in living primate oocytes and embryos using
      multiphoton microscopy.
AB  - We employed multiphoton laser scanning microscopy (MPLSM) to image changes in
      mitochondrial distribution in living rhesus monkey embryos. This method of
      imaging does not impair development; thus, the same specimen can be visualized
      multiple times at various developmental stages. Not only does this increase the
      amount of information that can be gathered on a single specimen but it permits
      the correlation of early events with subsequent development in the same specimen.
      Here we demonstrate the utility of MPLSM for determining changes in mitochondrial
      organization at various developmental stages and show that rhesus zygotes possess
      a distinct accumulation of mitochondria between the pronuclei prior to syngamy.
      We present evidence that suggests that this pronuclear accumulation may be
      positively correlated with development to the blastocyst stage-in the same embryo
      thereby illustrating how MPLSM can be used to correlate cellular dynamics of
      primate oocytes and early embryos with their developmental potential.
      Understanding the relationship between mitochondrial distribution and the
      subsequent development of mammalian embryos, particularly primates, will increase
      our ability to improve embryo culture technologies, including those used for
      human assisted reproduction.

PMID- 12807673
TI  - The correlation between ion beam/material interactions and practical FIB specimen
      preparation.
AB  - The focused ion beam (FIB) tool has been successfully used as both a stand alone
      analytical instrument and a means to prepare specimens for subsequent analysis by
      SEM, TEM, SIMS, XPS, and AUGER. In this work, special emphasis is given to TEM
      specimen preparation by the FIB lift-out technique. The fundamental ion/solid
      interactions that govern the FIB milling process are examined and discussed with
      respect to the preparation of electron transparent membranes. TRIM, a Monte Carlo
      simulation code, is used to physically model variables that influence FIB
      sputtering behavior. The results of such computer generated models are compared
      with empirical observations in a number of materials processed with an FEI 611
      FIB workstation. The roles of incident ion attack angle, beam current, trench
      geometry, raster pattern, and target-material-dependent removal rates are
      considered. These interrelationships are used to explain observed phenomena and
      predict expected milling behaviors, thus increasing the potential for the FIB to
      be used more efficiently with reproducible results.

PMID- 12807674
TI  - Characterization of contacting boundaries between nanoparticles with LACBED.
AB  - The boundary parameters between contacting spherical bcc-Fe particles have been
      characterized with the Large Angle Convergent Beam Electron Diffraction (LACBED)
      technique. The average accuracy of measurements can reach 0.07 degrees. The
      rotation parameters are interpreted using matrix algebra and evaluated according
      to the CSL model. The deviation between the experimental results and the
      reference misorientations given in the CSL model is determined. It is possible to
      reveal preferential misorientations between irregularly shaped particles with a
      size less than 100 nm. The method can be applied to nanoparticles and
      nanocrystalline materials with a wide range of grain orientations, and it is
      possible to modify it into an automatic method for TEM measurements.

PMID- 12807675
TI  - Electron radiation damage of MCM-41 and related materials.
AB  - The article compares the relative stability of MCM-41 and related mesoporous
      materials in electron beam at an accelerating voltage of 100-300 kV. The work
      encountered in electron microscopy presents a comparison with similar research
      that has been carried out on nonporous and microporous silicates, especially
      alpha-quartz and zeolite Y. The trends in stability are analyzed, classifying the
      effects of sample preparation, organic and inorganic moieties, and electron
      accelerating voltage on beam stability. A higher synthesis temperature, the use
      of an acid catalyst in the synthesis, and the presence of additional organic or
      inorganic material within the channels were all found to stabilize these
      materials. The dose required to completely disrupt the structure increased with
      accelerating voltage for nearly all samples, suggesting a primarily radiolytic
      damage mechanism. The exception, MCM-41 containing nanometer-sized titania
      particles in its channels, was found to be almost insensitive to accelerating
      voltage.

PMID- 12807686
TI  - What do we (not) know about the human bartonelloses?
AB  - The human bartonelloses are a group of diseases with a rapidly increasing
      clinical spectrum. Well known manifestations such as Carrion's disease, trench
      fever, cat-scratch disease, and bacillary angiomatosis are examples of Bartonella
      sp. infection. Along with these diseases, recurrent bacteremia, endocarditis,
      septicemia, erythema nodosum, erythema multiforme, trombocytopenic purpura and
      other syndromes have been reported having been caused by bacteria of this genus.
      The infectious process and the pathogenesis of these microorganisms are poorly
      understood. The bartonelloses may have a benign and self-limited evolution in a
      host, or a potentially fatal one. These bacteria can provoke a granulomatous or
      an angioproliferative histopathologic response. As these diseases are not yet
      well defined, we have reviewed the four main human bartonelloses and have
      examined unclear points about these emergent diseases.

PMID- 12807687
TI  - Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral
      agents in HIV-2 infection: a review.
AB  - Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) are the causative
      agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African
      countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is
      made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or
      two confirmatory tests specific for HIV-2. Following CD(4)(+)T cell counts, HIV-2
      viral burden and clinical signs and symptoms of immunodeficiency are beneficial
      in monitoring HIV-2 disease progression. Although non-nucleoside reverse
      transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse
      transcriptase inhibitors and protease inhibitors can be effective in dual and
      triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase
      CD(4)(+)T cell counts and improve AIDS-related symptoms. HIV-2 resistance to
      various nucleoside reverse transcriptase inhibitors and protease inhibitors,
      including zidovudine, lamivudine, ritonivir and indinavir, has been identified in
      some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2
      peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide
      the clinician in the choice of the initial antiretroviral regimen and for
      monitoring therapy success.

PMID- 12807688
TI  - AIDS-associated diarrhea and wasting in Northeast Brazil is associated with
      subtherapeutic plasma levels of antiretroviral medications and with both bovine
      and human subtypes of Cryptosporidium parvum.
AB  - Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel
      structure and function, and malnutrition. Resulting malabsorption of or
      pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic
      drug dosing and treatment failure in individual patients, and could require dose
      adjustment and/or dietary supplements during periods of diarrheal illness. We
      determined the plasma levels of antiretroviral medications in patients that had
      already been started on medication by their physicians, in an urban infectious
      diseases hospital in northeast Brazil. We also obtained blood samples from
      patients hospitalized for diarrhea or AIDS-associated wasting, and we found
      reduced stavudine and didanosine levels in comparison with outpatients without
      diarrhea or wasting who had been treated at the same hospital clinic. There was a
      predominance of the protozoal pathogens Cryptosporidium and Isospora belli,
      typical opportunistic pathogens of AIDS-infected humans, in the stool samples of
      inpatients with diarrhea. We conclude that severe diarrhea and wasting in this
      population is associated with both protozoal pathogens and subtherapeutic levels
      of antiretroviral medications.

PMID- 12807689
TI  - Pathogenicity mechanisms of prokaryotic cells: an evolutionary view.
AB  - The success of pathogenic microbes depends on their ability to colonize host
      tissues and to counter host defense mechanisms. Microorganisms can produce
      overwhelming infection because of their relatively short generation times, and
      because they have evolved powerful mechanisms for generating phenotypic diversity
      as an efficient strategy for adapting to rapidly responding immune system
      defenses and the broad range of polymorphisms characteristic of different host
      tissues. Bacterial evolution may not be a continuous process, but more of a
      succession of temporally spaced major events. These events cause a non-gradual
      sequence of adaptations to a given environment. The pathogenicity islands are
      genetically unstable elements, and many of the genes coding for the adhesins,
      toxins and other virulence factors are present in pathogenicity islands, which
      almost certainly had former lives as accessory elements or as parts thereof, or
      were borne on functional accessory elements. Novel genes are also acquired by
      transduction (mediated by bacteriophages, plasmids or transposons), by
      conjugation (DNA transfer between cells) or by transformation (natural DNA
      uptake). Horizontal gene transfer from other species is a major source of
      variation and is fundamental to the genetic theory of adaptive evolution in
      prokaryotes.

PMID- 12807690
TI  - Molecular techniques for MRSA typing: current issues and perspectives.
AB  - Staphylococcus aureus has long been recognised as an important pathogen in human
      disease. Serious staphylococcal infections can frequently occur in inpatients and
      may lead to dire consequences, especially for therapy with antimicrobial agents.
      The increase in the frequency of Methicillin-Resistant Staphylococcus aureus
      (MRSA) as the causal agent of nosocomial infection and the possibility of
      emergence of resistance to vancomycin demands a quick and trustworthy
      characterization of isolates and identification of clonal spread within
      hospitals. Enough information must be generated to permit the implementation of
      appropriate measures for control of infection, so that outbreaks can be
      contained. Molecular typing techniques reviewed in this manuscript include:
      plasmid profile analysis, analysis of chromosomal DNA after enzymatic
      restriction, Southern blotting, pulsed field gel electrophoresis (PFGE),
      techniques involving polymerase chain reaction and multilocus sequence typing
      (MLST). Repetitive DNA Sequence PCR (rep-PCR) may be used for screening due to
      its practicality, low cost and reproducibility. Because of its high
      discriminatory power Pulsed-Field Gel Electrophoresis (PFGE) still remains the
      gold standard for MRSA typing. New techniques with higher reproducibility and
      discriminatory power, such as Multi-Locus Sequence Typing (MLST), are appearing.
      These are mostly useful for global epidemiology studies. Molecular typing
      techniques are invaluable tools for the assessment of putative MRSA outbreaks and
      so should be extensively used for this purpose.

PMID- 12807691
TI  - Antibacterial resistance of community-acquired respiratory tract pathogens
      recovered from patients in Latin America: results from the PROTEKT surveillance
      study (1999-2000).
AB  - PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the
      Ketolide Telithromycin) is a global surveillance study established in 1999 to
      monitor antibacterial resistance of respiratory tract organisms. Thirteen centers
      from Argentina, Brazil and Mexico participated during 1999-2000; they collected
      1806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520,
      Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall,
      218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to
      penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin
      resistant. Mexico had the highest prevalence of penicillin (76.5%) and
      erythromycin (31.2%) resistance. Of 77 erythromycin-resistant S. pneumoniae
      tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1
      possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully
      susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H.
      influenzae isolates, 88 (16.9%) produced beta-lactamase, ranging from 11%
      (Brazil) to 24.5% (Mexico). Among M. catarrhalis isolates, 138 (98.6%) produced
      beta-lactamase. Twenty-four (8.7%) of the S. pyogenes isolates were erythromycin
      resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB
      (n=1). All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible
      to telithromycin. Methicillin resistance was found in 26.5% of the S. aureus
      isolates (Argentina 15%; Mexico 20%; Brazil 31.3%). Telithromycin was effective
      against 97.7% of methicillin-susceptible isolates. PROTEKT confirms that
      antibacterial resistance is an emerging problem in Latin America. The previously
      reported high levels of pneumococcal resistance to the beta-lactam and macrolides
      were exceeded. New agents that do not induce resistance or that exert low
      selective pressure, e.g. telithromycin, are essential to safeguard future
      antibacterial efficacy.

PMID- 12807692
TI  - An open label, multicenter, non-comparative study of the efficacy and safety of
      oral gatifloxacin in the treatment of community-acquired pneumonia: a Brazilian
      study in five centers.
AB  - We made an open label, multicenter, non-comparative study to assess the efficacy
      and safety of oral gatifloxacin, 400 mg PO given once-daily during 7 to 14 days
      for the treatment of adult outpatients with community-acquired pneumonia at five
      Brazilian medical facilities. Among the 86 subjects available for clinical
      evaluation, 84 (98%) were cured. The bacteriological eradication and presumed
      eradication rate was 98% (52/53) among the 44 (51%) patients who were
      bacteriologically evaluated. Drug-related adverse events were reported by 27% of
      the patients, diarrhea being the most frequent, occurring in 12% of patients.
      Adverse events were considered mild (89%) or moderate (11%). We conclude that a 7
      14 day course of gatifloxacin, 400 mg PO given once daily is safe and effective
      for the treatment of community-acquired pneumonia. The drug had a favorable
      safety profile and a good clinical and bacteriological efficacy.

PMID- 12807693
TI  - Prevalence of pathogens in cystic fibrosis patients in Bahia, Brazil.
AB  - INTRODUCTION: Recurrent respiratory infections account for most of the morbidity
      and mortality of cystic fibrosis patients. MATERIALS AND METHODS: The objective
      was to determine the prevalence of pathogens isolated from lower respiratory
      tract secretions in cystic fibrosis patients. In this descriptive observational
      study, data from 69 patients was collected from medical records. RESULTS: The
      microorganisms that were identified included 36.2 P. aeruginosa, 28.9% S. Aureus,
      4.3% K. pneumoniae, 1.5% H. influenzae, 1.5% E. coli, 1.5% S. maltoophilia, and
      in 27.5% the flora was normal. The prevalence of P. aeruginosa was 83% in
      patients under two years of age, demonstrating early colonization. CONCLUSION: P.
      aeruginosa and S. aureus were the most prevalent pathogens; there was also early
      infection/colonization by P. aeruginosa. This information will contribute to
      improved therapeutic measures for patients of the Bahia Cystic Fibrosis Reference
      Center.

PMID- 12807694
TI  - Clinical and radiological analysis of children and adolescents with tuberculosis
      in Bahia, Brazil.
AB  - We reviewed the clinical and radiological characteristics of tuberculosis (TB) in
      children and adolescents at the Hospital Especializado Octavio Mangabeira, (HEOM)
      in Salvador, Bahia. This study included 275 TB patients aged 1 to 15 years seen
      between January 1990 and November 2001. Standardized forms were filled out on the
      basis of a review of patient records and x-rays. Through a retrospective and
      descriptive analysis, it was found that 51.6% were male, 35.3% were aged 1 to 5
      years, 28% were aged 6 to 10 and 36.7% were aged 11 to 15. Among all patients,
      79.6% lived in the city of Salvador. A history of contact with TB was found in
      63.9%, most frequently among children under 5 years old; 77.2% were vaccinated
      with Bacillus Calmette-Guerin (BCG). The most frequently observed symptoms were
      coughing (76%), fever (73.1%) weight loss (53.1%), and 4.7% were asymptomatic.
      Pulmonary TB was most frequent (57.8%) and extra-pulmonary TB occurred in 24.4%,
      with a predominance of hilar adenopathy. Both forms occurred simultaneously in
      17.8%. In 53.1% of the cases the diagnosis was not determined by bacteriology or
      pathological anatomy; in these cases diagnosis was reached through clinical and
      radiological criteria, contact history, a tuberculin test > or = 10mm and a
      positive response to tuberculostatic drugs.

PMID- 12807695
TI  - The value of public health research and the division between basic vs. applied
      science.
AB  - We question the movement towards exclusion of population and social health
      research from the field of science. The background under analysis is contemporary
      Brazil, where the scientific field that hosts this kind of research is known as
      Collective Health. First, the problem is formalized on logical grounds,
      evaluating the pertinence of considering unscientific the many objects and
      methods of public health research. Secondly, the cases of pulmonary tuberculosis
      and external causes are brought in as illustrations of the kind of scientific
      problem faced in health research today. The logical and epistemological basis of
      different forms of "scientific segregation" based on biomedical reductionism is
      analyzed, departing from three theses: (i) the ethics of the general application
      of science; (ii) the inappropriateness of monopolies for objectivity in the
      sciences; (iii) the specificity of scientific fields. In the current panorama of
      health research in Brazil, a residual hegemonic position that defends a narrow
      and specific definition of the object of knowledge was found. The denial of
      validity and specificity to objects, methods and research techniques that
      constitute social and population research in health is linked to elements of
      irrationality in reductionism approaches. Nevertheless, efforts should be
      directed to overcome this scientific division, in order to develop a pluralist
      and interdisciplinary national science, committed to the health care realities of
      our country.

PMID- 12807696
TI  - Asthma intervention program prevents readmissions in high healthcare users.
AB  - The largest portion of the cost for asthma healthcare is due to hospitalizations.
      Improved methods of healthcare delivery for patients with asthma are needed to
      prevent readmissions. From 1996 to 1999, 96 adult subjects (predominantly young
      African American women) hospitalized with an asthma exacerbation, who had a
      history of frequent healthcare use, were randomized to an asthma nurse specialist
      intervention (n = 50) or a usual care group (n = 46) for 6 months. Our aim was to
      decrease rates of readmissions within 6 months of hospital discharge, to reduce
      cost, and to improve health-related quality of life. Our results demonstrate a
      60% reduction in total hospitalizations (31 readmissions in the intervention
      group and 71 in the control group, p = 0.04), with no significant change in
      emergency department visits. Readmissions for asthma were reduced by 54% (21 vs.
      42 in the control group; p = 0.04). We found a marked reduction in lost work or
      school days: 246 versus 1040 days in the control group (p = 0.02). The
      intervention resulted in a substantial reduction in direct and indirect
      healthcare costs, saving US dollars 6462 per patient (p = 0.03). A brief
      intervention program focusing on high healthcare users with asthma can result in
      improved asthma control and reduced hospital use with substantial cost savings.

PMID- 12807697
TI  - Bombesin-like peptides and mast cell responses: relevance to bronchopulmonary
      dysplasia?
AB  - Bombesin-like peptides (BLPs) are elevated in newborns who later develop
      bronchopulmonary dysplasia (BPD). In baboon models, anti-BLP blocking antibodies
      abrogate BPD. We now demonstrate hyperplasia of both neuroendocrine cells and
      mast cells in lungs of baboons with BPD, compared with non-BPD controls or BLP
      antibody-treated BPD baboons. To determine whether BLPs are proinflammatory,
      bombesin was administered intratracheally to mice. Forty-eight hours later, we
      observed increased numbers of lung mast cells. We analyzed murine mast cells for
      BLP receptor gene expression, and identified mRNAs encoding bombesin receptor
      subtype 3 and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide
      receptor. Only NMB-R-null mice accumulated fewer lung mast cells after bombesin
      treatment. Bombesin, gastrin-releasing peptide, NMB, and a bombesin receptor
      subtype 3-specific ligand induced mast cell proliferation and chemotaxis in
      vitro. These observations support a role for multiple BLPs in promoting mast cell
      responses, suggesting a mechanistic link between BLPs and chronic inflammatory
      lung diseases.

PMID- 12807700
TI  - Horizontal transfer of functional nuclear genes between multicellular organisms.

PMID- 12807698
TI  - Norepinephrine transport by the extraneuronal monoamine transporter in human
      bronchial arterial smooth muscle cells.
AB  - Inhaled glucocorticosteroids (GSs) cause acute, alpha1-adrenoreceptor (AR)
      mediated bronchial vasoconstriction. After release from sympathetic nerves,
      norepinephrine (NE) must be taken up into cells for deactivation by intracellular
      enzymes. Because postsynaptic cellular NE uptake is steroid sensitive, GSs could
      increase NE concentrations at alpha1-AR, causing vasoconstriction. We therefore
      evaluated mRNA expression of different NE transporters in human bronchial
      arterial smooth muscle and pharmacologically characterized NE uptake into these
      cells. RT-PCR demonstrated mRNA expression of the extraneuronal monoamine
      transporter (EMT) and organic cation transporter 1 (OCT-1). Fluorometric uptake
      assay showed time (within minutes)- and concentration-dependent NE uptake by
      freshly isolated bronchial arterial smooth muscle cells (SMC) with an estimated
      Km of 240 microM. Corticosterone and O-methylisoprenaline (1 microM each), but
      not desipramine, inhibited NE uptake, a profile indicative of NE uptake by EMT,
      but not OCT-1. Budesonide and methylprednisolone inhibited uptake with IC50
      values of 0.9 and 5.6 microM, respectively. Corticosterone's action was
      reversible and not sensitive to RU-486 (GS receptor antagonist), actinomycin D
      (transcription inhibitor), or cycloheximide (protein synthesis inhibitor).
      Corticosterone made membrane impermeant by coupling to BSA also blocked NE
      uptake. Immunocytochemistry indicated a specific membrane binding site for
      corticosterone on bronchial arterial SMC. These data demonstrate that although
      human bronchial arterial SMC express OCT-1 and EMT, EMT is the predominant plasma
      membrane transporter for NE uptake. This process can be inhibited by GSs, likely
      via a specific membrane binding site. This nongenomic GS action (increasing NE
      concentrations at alpha1-AR) could explain acute bronchial vasoconstriction
      caused by inhaled GSs.

PMID- 12807699
TI  - NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF
      alpha.
AB  - We tested the hypothesis that the NAD(P)H oxidase-dependent generation of
      superoxide anion (O2-*) mediates tumor necrosis factor-alpha (TNF)-induced
      alterations in the permeability of pulmonary microvessel endothelial monolayers
      (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue
      labeled albumin. The NAD(P)H oxidase subcomponents p47phox and p22phox were
      assessed by immunofluorescent microscopy and Western blot. The reactive oxygen
      species O2-* was measured by the fluorescence of 6-carboxy-2',7'
      dichlorodihydrofluorescein diacetatedi(acetoxymethyl ester), 5 (and 6)
      chloromethyl-2',7'-dichlorodihydrofluorescein diacetate-acetyl ester, and
      dihydroethidium. TNF treatment (50 ng/ml for 4.0 h) induced 1) p47phox
      translocation, 2) an increase in p22phox protein, 3) increased localization of
      p47phox with p22phox, 4) O2-* generation, and 5) increased permeability to
      albumin. p22phox antisense oligonucleotide prevented the TNF-induced effect on
      p22phox, p47phox, O2-*, and permeability. The scrambled nonsense oligonucleotide
      had no effect. The TNF-induced increase in O2-* and permeability to albumin was
      also prevented by the O2-* scavenger Cu-Zn superoxide dismutase (100 U/ml). The
      results indicate that the activation of NAD(P)H oxidase, via the generation of O2
      *, mediates TNF-induced barrier dysfunction in PMEM.

PMID- 12807701
TI  - Settlement cues in the locally dispersing temperate cup coral Balanophyllia
      elegans.

PMID- 12807702
TI  - Identification of asteroid genera with species capable of larval cloning.
AB  - Asexual reproduction in larvae, larval cloning, is a recently recognized
      component of the complex life histories of asteroids. We compare DNA sequences of
      mitochondrial tRNA genes (Ala, Leu, Asn, Pro, and Gln) from larvae in the process
      of cloning collected in the field with sequences from adults of known species in
      order to identify asteroid taxa capable of cloning. Neighbor-joining analysis
      identified four distinct groups of larvae, each having no, or very little,
      sequence divergence (p distances ranging from 0.00000 to 0.02589); thus, we
      conclude that each larval group most likely represents a single species. These
      field-collected larvae cannot be identified to species with certainty, but the
      close assemblage of known taxa with the four larval groups indicates generic or
      familial identity. We can assign two of the larval groups discerned here to the
      genera Luidia and Oreaster and another two to the family Ophidiasteridae. This
      study is the first to identify field-collected cloning asteroid larvae, and
      provides evidence that larval cloning is phylogenetically widespread within the
      Asteroidea. Additionally, we note that cloning occurs regularly and in multiple
      ways within species that are capable of cloning, emphasizing the need for further
      investigation of the role of larval cloning in the ecology and evolution of
      asteroids.

PMID- 12807703
TI  - Larval behavioral, morphological changes, and nematocyte dynamics during
      settlement of actinulae of Tubularia mesembryanthemum, Allman 1871 (Hydrozoa:
      Tubulariidae).
AB  - The marine colonial hydroid Tubularia mesembryanthemum produces a morphologically
      unique dispersive stage, the actinula larva. Detailed observations were made on
      the behaviors and nematocyte dynamics of actinula larvae during attachment and
      morphogenesis by employing microscopic and time lapse video techniques. These
      observations produced four primary results. (1) Actinula larvae demonstrated two
      forms of attachment: temporary attachment by atrichous isorhiza (AI)-nematocysts
      discharged from the aboral tentacle (AT) tips-and permanent settlement by cement
      secretion from the columnar gland cells of the basal protrusion. (2) During
      larval settlement, numerous AIs were discharged from the AT tips with sinuous
      movement and rubbing of the tentacles onto the substrata, leading to "nematocyte
      printing" around the settlement site. (3) Simultaneous with the discharge of the
      AIs, migration of stenoteles, desmonemes, and microbasic mastigophores occurred,
      resulting in a dramatic change of nematocyte composition in the ATs after larval
      settlement. This was in parallel with changes in larval behavior and the tentacle
      function. (4) Nematocyte-printing behavior during settlement could be recognized
      as metamorphic behavior responsible for irreversible changes in AT function, from
      attachment to feeding and defense.

PMID- 12807704
TI  - Energy metabolism during larval development of green and white abalone, Haliotis
      fulgens and H. sorenseni.
AB  - An understanding of the biochemical and physiological energetics of
      lecithotrophic development is useful for interpreting patterns of larval
      development, dispersal potential, and life-history evolution. This study
      investigated the metabolic rates and use of biochemical reserves in two species
      of abalone, Haliotis fulgens (the green abalone) and H. sorenseni (the white
      abalone). Larvae of H. fulgens utilized triacylglycerol as a primary source of
      endogenous energy reserves for development ( approximately 50% depletion from egg
      to metamorphic competence). Amounts of phospholipid remained constant, and
      protein dropped by about 30%. After embryogenesis, larvae of H. fulgens had
      oxygen consumption rates of 81.7 +/- 5.9 (SE) pmol larva(-1) h(-1) at 15 degrees
      C through subsequent development. The loss of biochemical reserves fully met the
      needs of metabolism, as measured by oxygen consumption. Larvae of H. sorenseni
      were examined during later larval development and were metabolically and
      biochemically similar to H. fulgens larvae at a comparable stage. Metabolic rates
      of both species were very similar to previous data for a congener, H. rufescens,
      suggesting that larval metabolism and energy utilization may be conserved among
      closely related species that also share similar developmental morphology and
      feeding modes.

PMID- 12807705
TI  - Localization and quantification of carbonic anhydrase activity in the symbiotic
      Scyphozoan Cassiopea xamachana.
AB  - The relationship between density and location of zooxanthellae and levels of
      carbonic anhydrase (CA) activity was examined in Cassiopea xamachana. In freshly
      collected symbiotic animals, high densities of zooxanthellae corresponded with
      high levels of CA activity in host bell and oral arm tissues. Bleaching resulted
      in a significant loss of zooxanthellae and CA activity. Recolonization resulted
      in full restoration of zooxanthellar densities but only partial restoration of CA
      activity. High levels of CA activity were also seen in structures with inherently
      higher zooxanthellar densities, such as oral arm tissues. Similarly, the oral
      epidermal layer of bell tissue had significantly higher zooxanthellar densities
      and levels of CA activity than did aboral bell tissues. Fluorescent labeling,
      using 5-dimethylaminonapthalene-1-sulfonamide (DNSA) also reflected this tight
      knit relationship between the presence and density of zooxanthellae, as DNSA-CA
      fluorescence intensity was greatest in host oral epithelial cells directly
      overlying zooxanthellae. However, the presence and density of zooxanthellae did
      not always correspond with enzyme activity levels. A transect of bell tissue from
      the margin to the manubrium revealed a gradient of CA activity, with the highest
      values at the bell margin and the lowest at the manubrium, despite an even
      distribution of zooxanthellae. Thus, abiotic factors may also influence the
      distribution of CA and the levels of CA activity.

PMID- 12807706
TI  - Reproductive behavior in the squid Sepioteuthis australis from South Australia:
      ethogram of reproductive body patterns.
AB  - Squids use a diverse range of body patterns for communication. Each pattern
      consists of a series of chromatic, postural, and locomotor components that are
      under neural control and can change within fractions of a second. Here we
      describe an ethogram of 48 body pattern components from in situ observations of
      reproductively active Sepioteuthis australis. In addition, we identify the total
      time and average duration that each component is shown, to a resolution of 1 s.
      Our results suggest that only a few components (e.g., "Golden epaulettes,"
      "Stitchwork fins," and "Rigid arms") are temporally common, that is, shown for
      more than 80% of the time. In contrast to the component classification reported
      for other species of squid, for this species we suggest a classification system
      consisting of "short acute" (lasting for < 10 s); some of these same components
      were also classified as "medium acute" (11-60 s) or "chronic" (> 60 s). Several
      body patterning components were previously unreported, as were some of the
      combinations observed. The significance of these patterning components is
      discussed within the context of the associated behaviors of the squid on the
      spawning grounds.

PMID- 12807707
TI  - Reproductive behavior in the squid Sepioteuthis australis from South Australia:
      interactions on the spawning grounds.
AB  - Squid behavior is synonymous with distinctive body patterns, postures, and
      movements that constitute a complex visual communication system. These
      communications are particularly obvious during reproduction. They are important
      for sexual selection and have been identified as a potential means of species
      differentiation. Here we present a detailed account of copulation, mating, and
      egg deposition behaviors from in situ observations of the squid Sepioteuthis
      australis from South Australia. We identified four mating types from 85 separate
      mating attempts: "Male-upturned mating" (64% of mating attempts); "Sneaker
      mating" (33%); "Male-parallel" (2%); and "Head-to-head" (1%). Intervals between
      successive egg deposition behaviors were clearly bimodal, with modes at 2.5 s and
      70.0 s. Ninety-three percent of egg capsules contained 3 or 4 eggs (mean = 3.54),
      and each egg cluster contained between 218 and 1922 egg capsules (mean = 893.9).
      The reproductive behavior of S. australis from South Australia was different from
      that described for other cephalopod species. More importantly, comparison between
      these results and those for other populations of S. australis suggests that
      behavior may differ from one population to another.

PMID- 12807708
TI  - Genetic differences within and between species of deep-sea crabs (chaceon) from
      the North Atlantic Ocean.
AB  - The deep-sea red crab Chaceon quinquedens is a commercially important crustacean
      on the Atlantic continental shelf and slope of North America. To assess genetic
      subdivision in C. quinquedens, we examined the nucleotide sequence of the
      mitochondrial 16S rDNA gene and the internal transcribed spacers (ITS) of the
      nuclear ribosomal repeat in samples from southern New England and the Gulf of
      Mexico. We compared those data to sequences from two congeners, a sympatric
      species from the Florida coast, C. fenneri, and an allopatric eastern Atlantic
      species, C. affinis. The 16S rDNA data consisted of 379 aligned nucleotides
      obtained from 37 individuals. The greatest genetic difference among geographical
      groups or nominal species was between C. quinquedens from southern New England
      and C. quinquedens from the Gulf of Mexico. Haplotypes from these two groups had
      a minimum of 10 differences. All 11 C. fenneri samples matched the most common
      haplotype found in C. quinquedens from the Gulf of Mexico, and this haplotype was
      not detected in C. quinquedens from southern New England. The three haplotypes of
      C. affinis were unique to that recognized species, but those haplotypes differed
      only slightly from those of C. fenneri and C. quinquedens from the Gulf of
      Mexico. Based on 16S rDNA and ITS data, genetic differences between C.
      quinquedens from southern New England and the Gulf of Mexico are large enough to
      conclude that these are different fishery stocks. Our results also indicate that
      the designation of morphological species within the commercially important genus
      Chaceon is not congruent with evolutionary history. The genetic similarity of C.
      affinis from the eastern Atlantic and C. quinquedens from the Gulf of Mexico
      suggests these trans-Atlantic taxa share a more recent common history than the
      two populations of "C. quinquedens" that we examined.

PMID- 12807709
TI  - Genetic linkage map of the eastern oyster Crassostrea virginica Gmelin.
AB  - Amplified fragment length polymorphisms (AFLPs), along with some microsatellite
      and Type I markers, were used for linkage analysis in Crassostrea virginica
      Gmelin, the eastern oyster. Seventeen AFLP primer combinations were selected for
      linkage analysis with two parents and their 81 progeny. The 17 primer
      combinations produced 396 polymorphic markers, and 282 of them were segregating
      in the two parents. Chi-square analysis indicated that 259 (91.8%) markers
      segregated in Mendelian ratio, while the other 23 (8.2%) showed significant (P <
      0.05) segregation distortion, primarily for homozygote deficiency and probably
      due to deleterious recessive genes. Moderately dense linkage maps were
      constructed using 158 and 133 segregating markers (including a few microsatellite
      and Type I markers) from male and female parents, respectively. The male
      framework map consisted of 114 markers in 12 linkage groups, covering 647 cM. The
      female map had 84 markers in 12 linkage groups with a length of 904 cM. The
      estimated genome length was 858 cM for the male map and 1296 cM for the female
      map. The observed genome coverage was 84% for the male and female map when all
      linked markers were considered. Genetic maps observed in this study are longer
      than the cytogenetic map, possibly because of low marker density.

PMID- 12807710
TI  - Use of multivariate analysis to assess the nutritional condition of fish larvae
      from nucleic acids and protein content.
AB  - The nutritional condition of turbot larvae (Scophthalmus maximus) was assessed by
      a multivariate analysis with DNA, RNA, and protein content as input variables.
      Special attention was given to the time that feeding began and to the timing and
      duration of starvation. The combination of the principal components analysis and
      the stepwise discriminant analysis, both techniques of multivariate analysis,
      made it possible to allocate the larvae into groups that were defined and
      identified based on similarities in developmental stage and nutritional
      condition. The developmental stage was mostly determined by the input variables
      DNA and protein content, while nutritional condition was determined by the RNA
      content. In the period studied, the more developed larvae were less resistant to
      starvation. Furthermore, when initial feeding was delayed as little as 6 h, the
      variables analyzed were markedly changed, and the effect on the deprived larvae
      was found to be equivalent to a 3-day delay in development-when compared with the
      larvae fed immediately after mouth opening. Through this technique, new samples
      of larvae with unknown history might be classified into groups, using their DNA,
      RNA, and protein content as input values in the defined classification functions.
      Results were compared to those obtained using RNA/DNA and RNA/dry weight indices,
      and the multivariate method was considered to be more sensitive and to provide
      extra information about larval nutritional history and development.

PMID- 12807711
TI  - Type 2 diabetes and coronary heart disease: we keep learning how little we know.

PMID- 12807712
TI  - c-Src and smooth muscle NAD(P)H oxidase: assembling a path to hypertrophy.

PMID- 12807713
TI  - Thrombin and vascular development: a sticky subject.
AB  - Formation of the vasculature is an essential step in embryogenesis. It was
      observed decades ago that the vasculature and the intravascular blood
      compartment, which uses the former as a means of transportation, develop in a
      close spatial and temporal relationship. In this review, we discuss the role of
      the blood coagulation system as a tool to coordinate angiogenesis. Several mouse
      models lacking coagulation factors result in impaired thrombin generation and
      display a phenotype of disturbed cardiovascular development. Similar phenotypes
      are observed in mouse models of impaired thrombin binding to its cellular
      receptor, protease-activated receptor-1, or of disrupted signaling via G
      proteins. Most interestingly, the available data provide evidence that thrombin
      signaling in vascular development cannot be explained by a model based only on
      the classic extrinsic and intrinsic coagulation pathways. Because angiogenesis in
      adults follows the same signaling patterns as angiogenesis in embryos, it is
      important to learn about these pathways, hoping that they may serve as
      therapeutic targets in cardiovascular disease.

PMID- 12807714
TI  - A peculiar result and a fanciful hypothesis regarding L-arginine.

PMID- 12807715
TI  - Should soluble CD40 ligand be measured from serum or plasma samples?

PMID- 12807717
TI  - The latent membrane protein 1 of Epstein-Barr virus and loss of the INK4a locus:
      paradoxes resolve to cooperation in carcinogenesis in vivo.
AB  - Nasopharyngeal carcinoma (NPC) is the most tightly Epstein-Barr virus (EBV)
      associated tumour. The EBV oncoprotein latent membrane protein 1 (LMP1) is
      frequently expressed in NPC tumours and may play a role in the genesis of the
      disease. NPC tumours often exhibit loss of expression (by deletion or
      methylation) of the INK4a locus, which encodes the tumour suppressor genes
      p16INK4a and p14ARF. To investigate the contribution of LMP1 and INK4a loss to
      tumourigenesis, skin chemical carcinogenesis was conducted using PyLMP1 and INK4a
      null mice. Surprisingly, INK4a null mice developed significantly fewer papillomas
      than wild-type mice, nevertheless, the papillomas that did develop grew faster
      and converted more rapidly to carcinoma than controls. This indicates that while
      loss of the INK4a locus plays an important role in the later stages of
      tumourigenesis, initially its loss inhibits papilloma formation. Conversely, LMP1
      promoted papilloma formation but paradoxically inhibited papilloma growth. Using
      cross-breeds, it was found that LMP1 cooperates with loss of the INK4a locus
      during epithelial tumourigenesis. The expression of LMP1 overcame the inhibition
      of papilloma formation observed in INK4a null mice, whilst the loss of the INK4a
      locus counteracted the inhibition of papilloma growth rate found in PyLMP1 mice.
      This suggests that LMP1 mediates the inhibition of papilloma growth via one or
      both of the INK4a locus products. Intriguingly, mice heterozygous for INK4a loss
      showed lesion growth rates intermediate between wild-type and null, demonstrative
      of haploinsufficiency. We propose that LMP1 acts at the early stages in
      carcinogenesis to promote the development of benign tumours and that early
      reduction of INK4a locus expression allows these lesions to expand in size. In
      addition, loss of the INK4a locus accelerates the development of a more
      aggressive lesion. Conversely, complete loss of the INK4a locus in an otherwise
      normal cell might inhibit lesion formation.

PMID- 12807718
TI  - Radiation-induced deletions in the 5' end region of Notch1 lead to the formation
      of truncated proteins and are involved in the development of mouse thymic
      lymphomas.
AB  - Notch1 protein is a transmembrane receptor that directs various cell fate
      decisions. Active forms of Notch1 consisting of a transmembrane domain and an
      intracellular domain (Notch1TM) or only an intracellular domain (Notch1IC)
      function as oncoproteins. To elucidate the effect of Notch1 abnormalities in
      radiation-induced lymphomagenesis, we determined the structure of the Notch1 gene
      and examined the frequency and the sites of Notch1 rearrangements in radiation
      induced mouse thymic lymphomas. The Notch1 gene consists of 37 exons, including
      three exons upstream of the previously reported exon 1. The transcript starting
      from exon 1 was the major transcript whereas the transcripts read upstream from
      exon 1a, in which amino acid sequences in the N-terminal region were changed,
      were minor. More than 50% of radiation-induced thymic lymphomas exhibited Notch1
      rearrangements, suggesting that Notch1 acts as a major oncogene in radiation
      induced lymphomagenesis. We identified three rearranged sites: novel sites in the
      5' end region encompassing exons 1 and 2, the previously identified juxtamembrane
      extracellular region, and the 3' end region. The 5' deletion and the insertion of
      murine leukemia virus in the juxtamembrane region led to the production of
      abnormal transcripts starting from cryptic transcription start sites located
      halfway through the Notch1 gene and resulted in transcripts lacking most of the
      extracellular domain. As a result of these rearrangements, truncated Notch1
      polypeptides resembling Notch1TM or Notch1IC were formed. In contrast, the 3'
      deletion led to the production of a C-terminal PEST motif-deleted transcript. The
      downstream target gene Hes1 was transcribed in a lymphoma with insertion of
      murine leukemia virus, but not in a lymphoma with a 5' deletion. These results
      indicate that in addition to Hes1 expression, other Notch1 pathway(s) have a role
      in thymic lymphomagenesis and suggest the presence of a novel mechanism for
      oncogenic activation of Notch1 by 5' deletion.

PMID- 12807719
TI  - Growth and angiogenesis of human breast cancer in a nude mouse tumour model is
      reduced by NK4, a HGF/SF antagonist.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a cytokine primarily produced
      by stromal fibroblasts and is a known angiogenic and invasion-inducing factor. It
      is increased in patients with breast cancer. This study examined the effect of
      NK4, a newly described HGF/SF antagonist, on HGF/SF-promoted growth of a human
      breast cancer. Both in vitro (invasion and migration assays) and in vivo (murine
      tumour model) methods were used to ascertain the effect of NK4 on HGF/SF from two
      sources: human fibroblast-derived HGF/SF and recombinant HGF/SF. In the in vitro
      invasion assay and migration assay, both HGF/SF and human fibroblasts, which
      secrete bioactive HGF/SF, increased the invasiveness and migration of the breast
      cancer cells (MDA MB 231). NK4 significantly reduced this invasiveness and
      motility. In the animal model, tumour volume and weight was significantly reduced
      with addition of NK4. It also suppressed HGF/SF-induced growth and markedly
      retarded tumour growth induced by fibroblasts (MRC5), secreting bioactive HGF/SF.
      Tumour angiogenesis was assessed by immunohistochemical staining of primary
      tissue sections using VE-cadherin (an endothelial cell specific cell-cell
      adhesion molecule). Again, NK4 reduced the effects of both HGF/SF and
      fibroblasts. We conclude that NK4 has a significant effect on the growth of human
      breast tumours in nude mice, particularly when stimulated by HGF/SF or
      fibroblasts. This may occur by decreasing angiogenesis. This gives a clear
      indication of the therapeutic worth of NK4.

PMID- 12807720
TI  - The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a
      suppresses polyp formation in Apc(Min/+) mice.
AB  - P-glycoprotein (P-gp) mediates the active transport of various substrates
      including xenobiotics, and it thus has a protective function in various cell
      types and tissues/organs including the intestinal epithelium. However, whether or
      not P-gp plays a positive role in the intestinal tumorigenesis is unclear. We
      have introduced disrupted alleles of the murine P-gp gene, mdr1a, into Apc(Min/+)
      mice to evaluate whether P-gp plays any role in intestinal carcinogenesis.
      Spontaneously occurring DNA damage was significantly increased in both the small
      and large intestine of mdr1a(-/-), Apc(Min/+) mice compared with mdr1a(+/+),
      Apc(Min/+) mice. Furthermore, we observed active proliferation and rapid
      migration/disappearance of enterocytes in the intestine of the compound mice
      deficient in mdr1a. Finally, we found that the number of polyps and cancers was
      markedly decreased in mdr1a(-/-), Apc(Min/+) mice (P=0.0016). P-gp thus appears
      to play a positive role during intestinal tumorigenesis.

PMID- 12807721
TI  - Human invasive trophoblasts transformed with simian virus 40 provide a new tool
      to study the role of PPARgamma in cell invasion process.
AB  - Invasive cytotrophoblasts play a key role in the development of human placenta
      and is therefore essential for subsequent development of the embryo. Human
      implantation is characterized by a major trophoblastic invasion that offers a
      unique model of a controlled and oriented tumor-like process. The ligand
      activated nuclear receptor peroxisome proliferator-activated receptor gamma
      (PPARgamma) modulates cell growth and differentiation and might be therefore
      considered as a tumor suppressor. We have recently reported that PPARgamma, in
      synergy with its dimerization partner retinoid X receptor (RXR)alpha, controls
      the invasion of human primary cytotrophoblasts. Because these cells are unable to
      replicate in culture, we have, in the present study, transformed these primary
      cells with the simian virus 40 large T antigen for studying the role of PPARgamma
      in cell invasion process. Our results show that the cell line human invasive
      proliferative extravillous cytotrophoblast (HIPEC) 65 expressed markers of human
      invasive primary cytotrophoblast as determined by immunocytochemistry,
      immunobloting and real-time RT-PCR, and were highly invasive in vitro. We have
      next studied the role of PPARgamma/RXRalpha heterodimers in cell proliferation
      and invasion. Our results show that PPARgamma and RXRalpha are co-expressed by
      HIPEC 65 and that, as commonly observed, activation of PPARgamma/RXRalpha
      heterodimers with the specific PPARgamma agonist rosiglitazone induced lipid
      droplet accumulation as revealed by oil red O staining. Treatment with
      rosiglitazone or with the natural PPARgamma agonist 15-deoxy-delta-(12,14) PGJ2
      did not modify cell growth, but interestingly, activation of PPARgamma by this
      synthetic (rosiglitazone) or natural (15d-PGJ2) ligand markedly inhibited cell
      invasion in a concentration-dependent manner. Finally, we showed that other
      potential natural PPARgamma ligand such as oxidized-but not native-low-density
      lipoprotein inhibited cell invasion. This proliferative and invasive human
      cytotrophoblast cell line from extravillous origin provides a new tool for
      studying specifically the role of PPARgamma in the control of cell invasion.

PMID- 12807722
TI  - HMGA1 protein over-expression is a frequent feature of epithelial ovarian
      carcinomas.
AB  - High mobility group A 1 (HMGA1) proteins are chromatinic factors, which are
      absent or expressed at very low levels in normal adult tissues, while they are
      over-expressed in several human malignant tumors. In this study, HMGA1 protein
      expression was investigated by immunohistochemistry in a series of 44 epithelial
      ovarian specimens, which included four normal ovarian tissues, 29 primary
      invasive carcinomas, one metastatic ovarian tumor and 10 low malignant potential
      (LMP) tumors. HMGA1 staining was not detected in normal ovarian surface
      epithelium, which is the area from which ovarian adenocarcinoma frequently
      arises. HMGA1 proteins were expressed at low levels in some LMP tumors, whereas
      they were present in abundance in most of the primary ovarian adenocarcinomas. RT
      PCR and western blot analysis correlated with immunohistochemical data. We
      demonstrated that the suppression of HMGA1 protein synthesis by an adenovirus
      carrying the HMGA1 gene in antisense orientation (Ad-Yas-GFP) inhibited the
      growth of two human ovarian carcinoma cell lines (OVCAR-5 and OVCAR-8). These
      results confirm HMGA1 over-expression as a general feature of human malignant
      neoplasias, including ovarian cancer and suggest that suppression of HMGA1
      protein synthesis by an antisense adenoviral vector may represent a new and
      promising gene therapy for the treatment of ovarian cancer.

PMID- 12807723
TI  - Extended lifespan of Barrett's esophagus epithelium transduced with the human
      telomerase catalytic subunit: a useful in vitro model.
AB  - As there has been no previous information on the consequences of telomerase
      expression in genetically altered, mortal cells derived from pre-malignant
      tissue, we sought to determine the effect of hTERT (human catalytic subunit of
      telomerase reverse transcriptase) transduction of pre-malignant cell strains from
      Barrett's esophagus that do not contain telomerase activity and possess a finite
      lifespan. Primary cultures of Barrett's esophageal epithelium transduced with a
      retrovirus containing hTERT were characterized by growth factor requirements,
      cytogenetics and flow cytometry. Expression of telomerase lengthened telomeres
      and greatly extended the lifespan of hTERT transduced (hTERT+) Barrett's
      esophagus cells. Growth factor dependency of the hTERT+ cultures remained largely
      similar to the parental cultures, although there was a modest increase in the
      ability to grow in agar. Chromosomal instability, measured by both karyotypic and
      FISH (fluorescence in situ hybridization) analyses, was reduced but not abrogated
      by hTERT transduction, suggesting that telomerase expression can enhance genomic
      stability. However, the persistence of residual instability gave rise to new
      clonal and non-clonal genetic variants, and in one hTERT+ culture a new DNA
      aneuploid population was observed, the only time such a ploidy shift has been
      seen in Barrett's cell strains in vitro. These in vitro observations are
      analogous to the clinical progression to aneuploidy that often precedes cancer in
      Barrett's esophagus, and suggest that reactivation of telomerase may be
      permissive for continued genetic evolution to cancer. Long-lived Barrett's
      esophagus epithelial cultures should provide a useful in vitro model for studies
      of neoplastic evolution and chemopreventive therapies.

PMID- 12807724
TI  - Mechanisms by which energy restriction inhibits rat mammary carcinogenesis: in
      vivo effects of corticosterone on cell cycle machinery in mammary carcinomas.
AB  - Increased secretion of adrenal cortical steroids may account in part for its
      cancer inhibitory activity of energy restriction (ER). To test this hypothesis, a
      study was conducted to determine the effects of dietary administration of
      corticosterone on the post-initiation stage of mammary carcinogenesis. Eighty
      four female Sprague-Dawley rats were injected with 50 mg 1-methyl-1
      nitrosourea/kg body wt (i.p.) at 21 days of age. One week later, animals were
      randomly divided into three groups and fed control diet, or that diet to which
      was added 200 or 400 mg corticosterone/kg. Diets were fed for 5 weeks after which
      the experiment was terminated. With increasing dietary corticosterone, a dose
      dependent reduction in the incidence (P=0.03), multiplicity (P=0.003) and size
      (P<0.003) of mammary carcinomas was observed. Dietary administration of
      corticosterone also reduced plasma insulin-like growth factor-1 (IGF-1) and
      levels of IGF-1 receptor in mammary carcinomas (P<0.01). In order to investigate
      molecular mechanisms underlying anticancer activity, the levels and activities of
      cell cycle components involved in the G1-S transition were investigated in
      mammary carcinomas that emerged in treated animals. Levels of cyclin D1, cyclin
      E, cyclin-dependent kinase (CDK)-2 and CDK-4 were reduced in carcinomas from
      corticosterone treated rats; whereas, levels of cyclin-dependent kinase
      inhibitors (CKI) Kip1/p27 and Cip1/p21 were elevated. Binding of these CKIs to
      both the cyclin D1-CDK-4 complex and the cyclin E-CDK-2 complex were increased
      and the kinase activities of these complexes were reduced with increasing dietary
      corticosterone. These effects were consistent with those observed in response to
      ER in vivo and corticosterone exposure in vitro. Whereas the effects of
      exogenously administered corticosterone and ER had many similarities, the lower
      efficacy of corticosterone versus ER in inhibiting the carcinogenic process imply
      that changes in cortical steroid metabolism alone are unlikely to explain the
      cancer inhibitory activity of ER.

PMID- 12807725
TI  - Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB
      activation through inhibition of IkappaBalpha kinase in human lung epithelial
      cells: correlation with suppression of COX-2, MMP-9 and cyclin D1.
AB  - Cigarette smoke (CS) is a major cause of a variety of malignancies including
      cancers of the larynx, oral cavity and pharynx, esophagus, pancreas, kidney,
      bladder and lung. The signal transduction pathway that mediates the effects of CS
      is not well understood but nuclear factor-kappa B (NF-kappaB) is probably
      involved. The gas phase of CS contains free radicals such as superoxide radicals,
      hydroxyl radicals and hydrogen peroxide, which potentially can activate NF
      kappaB. Benzo[a]pyrene, another potent carcinogen of CS, can also activate NF
      kappaB, but by an as yet unknown mechanism. Various other agents that activate NF
      kappaB are either tumor initiators or tumor promoters, and NF-kappaB activation
      can block apoptosis, promote proliferation and mediate tumorigenesis. Therefore,
      NF-kappaB is an ideal target for preventing CS-induced lung carcinogenesis. Thus,
      agents that abrogate NF-kappaB activation have the potential to suppress lung
      carcinogenesis. Because curcumin, a diferuloylmethane, is anticarcinogenic, we
      investigated the effect of this phytochemical on CS-induced NF-kappaB activation
      and NF-kappaB-regulated gene expression in human non-small cell lung carcinoma
      cells. Exposure of cells to CS induced persistent activation of NF-kappaB, and
      pre-treatment with curcumin abolished the CS-induced DNA-binding of NF-kappaB,
      IkappaBalpha kinase activation, IkBalpha phosphorylation and degradation, p65
      nuclear translocation and CS-induced NF-kappaB-dependent reporter gene
      expression. The inhibition of NF-kappaB activation correlated with suppression of
      CS-induced NF-kappaB-dependent cyclin D1, cyclooxygenase-2 and matrix
      metalloproteinase-9 expression. Overall our results indicate that CS-induced NF
      kappaB activation and NF-kappaB-regulated gene expression in human non-small cell
      lung carcinoma cells is suppressed by curcumin through suppression of
      IkappaBalpha kinase.

PMID- 12807726
TI  - Phenobarbital at low dose exerts hormesis in rat hepatocarcinogenesis by reducing
      oxidative DNA damage, altering cell proliferation, apoptosis and gene expression.
AB  - Our recent research indicated that phenobarbital (PB) may inhibit the development
      of N-diethylnitrosamine (DEN)-initiated pre-neoplastic lesions at low doses in a
      rat liver medium-term bioassay (Ito test), while high doses exhibit promoting
      activity. This raises the question of whether treatment with low doses of PB
      might reduce cancer risk. For clarification, male 6-week-old F344 rats were
      treated with PB at doses of 0, 2, 15 and 500 p.p.m. in the diet for 10 or 33
      weeks after initiation of hepatocarcinogenesis with DEN. In a second, short-term
      experiment, animals were given PB at doses of 2, 4, 15, 60 and 500 p.p.m. for 8
      days. Formation of glutathione S-transferase placental form (GST-P) positive foci
      and liver tumors was inhibited at 2 p.p.m. Generation of oxidative DNA damage
      marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG), cellular proliferation within the
      areas of GST-P positive foci and apoptosis in background liver parenchyma were
      suppressed. Suppression of 8-OHdG formation by PB at low dose might be related to
      the enhanced mRNA expression of 8-OHdG repair enzyme, oxoguanine glycosylase 1
      (Ogg1). Moreover, as detected by cDNA microarray analysis, PB treatment at low
      dose enhanced mRNA expression of glutamic acid decarboxylase (GAD65), an enzyme
      involved in the synthesis of gamma-aminobutyric acid (GABA), and suppressed MAP
      kinase p38 and other intracellular kinases gene expression. On the contrary, when
      PB was applied at a high dose, GST-P positive foci numbers and areas, tumor
      multiplicity, hydroxyl radicals and 8-OHdG levels were greatly elevated with the
      increase in CYP2B1/2 and CYP3A2 mRNA, protein, activity and gene expression of
      GST, nuclear tyrosine phosphatase, NADPH- cytochrome P-450 reductase and guanine
      nucleotide binding protein G(O) alpha subunit. These results indicate that PB
      exhibits hormetic effect on rat hepatocarcinogenesis initiated with DEN by
      differentially altering cell proliferation, apoptosis and oxidative DNA damage at
      high and low doses.

PMID- 12807727
TI  - Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis
      through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP,
      the release of cytochrome c and inhibition of Akt.
AB  - Curcumin, a natural, biologically active compound extracted from rhizomes of
      Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor
      and anti-oxidative properties. The mechanism by which curcumin initiates
      apoptosis remains poorly understood. In the present report we investigated the
      effect of curcumin on the activation of the apoptotic pathway in human renal Caki
      cells. Treatment of Caki cells with 50 microM curcumin resulted in the activation
      of caspase 3, cleavage of phospholipase C-gamma1 and DNA fragmentation. Curcumin
      induced apoptosis is mediated through the activation of caspase, which is
      specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp
      fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA
      fragmentation of Caki cells, which is preceded by the sequential
      dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and
      IAP proteins, release of cytochrome c and activation of caspase 3. Cyclosporin A,
      as well as caspase inhibitor, specifically inhibit curcumin-induced apoptosis in
      Caki cells. Pre-treatment with N-acetyl-cysteine, markedly prevented
      dephosphorylation of Akt, and cytochrome c release, and cell death, suggesting a
      role for reactive oxygen species in this process. The data indicate that curcumin
      can cause cell damage by inactivating the Akt-related cell survival pathway and
      release of cytochrome c, providing a new mechanism for curcumin-induced
      cytotoxicity.

PMID- 12807728
TI  - Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin
      E2, interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut
      extract and arecoline.
AB  - Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus
      fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of
      cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 micro
      g/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF
      alpha production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated
      PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 micro g/ml)
      also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast,
      arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81
      and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 micro g/ml
      AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at
      concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800
      micro g/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein
      production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but
      enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 micro g/ml) and
      anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell
      growth. Incubation of GK and KB cells with aspirin, anti-IL-6 ab and anti-TNF
      alpha ab showed little effect on arecoline- and AN-induced cytotoxicity, cell
      cycle arrest and apoptosis. Exposure to anti-TNF-alpha ab slightly affected
      arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells.
      Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+
      and CD8+ T cell activation. These results indicate that BQ chewing contributes to
      the pathogenesis of cancer and OSF by impairing T cell activation and by
      induction of PGE2, TNF-alpha and IL-6 production, which affect oral mucosal
      inflammation and growth of OMF and oral epithelial cells.

PMID- 12807729
TI  - Transcriptional regulation of the telomerase hTERT gene as a target for cellular
      and viral oncogenic mechanisms.
AB  - Malignant transformation from mortal, normal cells to immortal, cancer cells is
      generally associated with activation of telomerase and subsequent telomere
      maintenance. A major mechanism to regulate telomerase activity in human cells is
      transcriptional control of the telomerase catalytic subunit gene, human
      telomerase reverse transcriptase (hTERT). Several transcription factors,
      including oncogene products (e.g. c-Myc) and tumor suppressor gene products (e.g.
      WT1 and p53), are able to control hTERT transcription when over-expressed,
      although it remains to be determined whether a cancer-associated alteration of
      these factors is primarily responsible for the hTERT activation during
      carcinogenic processes. Microcell-mediated chromosome transfer experiments have
      provided evidence for endogenous factors that function to repress the telomerase
      activity in normal cells and are inactivated in cancer cells. At least one of
      those endogenous telomerase repressors, which is encoded by a putative tumor
      suppressor gene on chromosome 3p, acts through transcriptional repression of the
      hTERT gene. The hTERT gene is also a target site for viruses frequently
      associated with human cancers, such as human papillomavirus (HPV) and hepatitis B
      virus (HBV). HPV E6 protein contributes to keratinocyte immortalization and
      carcinogenesis through trans-activation of the hTERT gene transcription. In at
      least some hepatocellular carcinomas, the hTERT gene is a non-random integration
      site of HBV genome, which activates in cis the hTERT transcription. Thus, a
      variety of cellular and viral oncogenic mechanisms converge on transcriptional
      control of the hTERT gene. Regulation of chromatin structure through the
      modification of nucleosomal histones may mediate the action of these cellular and
      viral mechanisms. Further elucidation of the hTERT transcriptional regulation,
      including identification and characterization of the endogenous repressor
      proteins, should lead to better understanding of the complex regulation of human
      telomerase in normal and cancer cells and may open up new strategies for
      anticancer therapy.

PMID- 12807730
TI  - CpG methylation-dependent repression of the human O6-methylguanine-DNA
      methyltransferase gene linked to chromatin structure alteration.
AB  - The mechanism of inactivation of the O6-methylguanine-DNA methyltransferase
      (MGMT), responsible for repair of mutagenic and cytotoxic O6-alkylguanine, in Mex
      tumor cells, is not completely understood. We have examined the role of CpG
      methylation in the human MGMT promoter in a luciferase (luc) reporter plasmid and
      associated alteration in chromatin structure. Methylation of 16% CpG sequences in
      promoter and flanking sequences in the plasmid with HpaII methylase reduced
      luciferase activity by 10-12-fold, while methylation of all CpG sites, including
      those in the luc coding sequence, as well as the promoter sequence blocked
      expression completely. Repression of luc expression due to partial but not
      complete CpG methylation could be reversed by histone deacetylase inhibitor
      trichostatin A (TSA). However, 5-azacytidine, which reverses CpG methylation, but
      not TSA, could reactivate silent MGMT gene in Mex- HeLa MR cells. Furthermore,
      chromatin immunoprecipitation (ChIP) assay showed reduced level of acetylation of
      H4 histone bound to the methylated promoter compared with the non-methylated
      promoter. These results suggest that complete repression of the MGMT gene in Mex-
      cells requires methylation of CpG sequences in both promoter and neighboring
      regions of the gene, resulting in inactive, condensed chromatin state of the
      gene.

PMID- 12807731
TI  - Molecular dosimetry of N7-(2-hydroxypropyl)guanine in tissues of F344 rats after
      inhalation exposure to propylene oxide.
AB  - Propylene oxide (PO) is a high-volume chemical intermediate that causes a low
      incidence of nasal tumors in rodents exposed to high concentrations (> or =300
      p.p.m.). PO reacts with DNA forming mainly N7-(2-hydroxypropyl)guanine (7-HPG).
      The exposure-dependent accumulation of 7-HPG in nasal respiratory epithelium
      (NRE), lung and liver was determined in male F344 rats exposed to PO (0, 5, 25,
      50, 300 or 500 p.p.m.) by the inhalation route for 3 or 20 days (6 h/day; 5
      days/week). These exposures ranged from low concentrations, such as those
      potentially occurring in the workplace, to high concentrations that proved to be
      carcinogenic in rodents. Analysis of 7-HPG in DNA by gas chromatography-high
      resolution mass spectrometry (GC-HRMS) showed a linear response in 7-HPG for all
      three tissues after 3 days of exposure, and for NRE and lung after 20 days of
      exposure. A slightly sublinear response in 7-HPG was observed in liver after 20
      days of exposure. For both exposure periods, the NRE had the highest
      concentration of 7-HPG, followed by lung and liver. The amount of 7-HPG in NRE
      was seven and 17 times higher than in lung and liver, respectively, for the 3 day
      exposures. For the 20 day exposures, the concentration of 7-HPG in NRE was six
      and 13 times higher than that in lung and liver, respectively, over the
      concentration range studied. These results demonstrate a much higher extent of
      DNA alkylation in the target tissue for carcinogenesis, than in non-target
      tissues. As PO-induced tumor formation was highly sublinear, occurring only at
      high vapor concentrations, whereas 7-HPG adducts were shown to be linearly
      dependent on airborne concentration, these results suggest that 7-HPG is not
      sufficient for PO nasal carcinogenesis and that other factors such as increased
      cell proliferation may be important in determining the tumor exposure response.

PMID- 12807732
TI  - Single amino acid mutations, but not common polymorphisms, decrease the activity
      of CYP1B1 against (-)benzo[a]pyrene-7R-trans-7,8-dihydrodiol.
AB  - Genetic differences that underlie inter-individual variation in the metabolism of
      common carcinogens are important potential sources of cancer susceptibility.
      Cytochrome P450 1B1 (CYP1B1), a central enzyme in the activation of the
      ubiquitous environmental carcinogen benzo[a]pyrene (B[a]P), has several genetic
      variants. This study investigated six rare mutations and four common
      polymorphisms for their effects on B[a]P metabolism. Five missense mutations
      associated with congenital glaucoma (Gly61Glu, Gly365Trp, Asp374Asn, Pro437Leu
      and Arg469Tryp) dramatically decreased the capacity of CYP1B1 to convert (
      )benzo[a]pyrene-7R-trans-7,8-dihyrodiol (B[a]P-7,8-diol) to (+/-)benzo[a]pyrene-r
      7,t-8-dihydrodiol-9,10-epoxides. These five mutations resulted in enzymes with 3
      12% of normal activity when assayed in vitro using an Saccharomyces cerevisiae
      microsomal expression system. A 10 bp deletion mutation produced no detectable
      protein or activity. In contrast, proteins containing all possible combinations
      of four common single nucleotide polymorphisms (Arg48Gly, Ala199Ser, Val432Leu,
      Asn453Ser) had modest effects on B[a]P-7,8-diol metabolism. Michaelis-Menten
      analysis suggested that two alleles, Arg48, Ala119, Val432, Ser453 (RAVS) and
      Arg48, Ala119, Leu432, Ser453 (RALS), have KM values 2-fold lower than Arg48,
      Ala119, Val432, Ser453 (RAVN): 1.4+/-0.3 and 1.3+/-0.4 microM, respectively,
      compared with 2.8+/-0.8 microM (P<0.05). However, these differences could not be
      confirmed with direct measurements of rate at low substrate concentration. There
      were no significant differences for either of two other kinetic parameters, kcat
      or kcat/KM. Allele frequency analysis in three populations reveals the Ser453
      variant is rare among those of Asian (<1%) and African ancestry (<4%), and more
      common in individuals of European ancestry (16%). Haplotypes containing the
      Ser453 variant were uncommon; only RALS was detectable in our small populations.
      The RALS allele occurred between 0.5% in Asians and 15% in Europeans. Our study
      demonstrates that rare, disease-associated mutations in CYP1B1 significantly
      decrease the enzyme's metabolism of B[a]P-7,8-diol; however, our results do not
      identify any major differences in this metabolism due to four common single amino
      acid polymorphisms.

PMID- 12807733
TI  - Oncogenic and invasive potentials of human macrophage-stimulating protein
      receptor, the RON receptor tyrosine kinase.
AB  - The product of the RON (recepteur d'origine nantais) gene belongs to the MET
      proto-oncogene family, a distinct subfamily of receptor tyrosine kinases. The
      ligand of RON was identified as macrophage-stimulating protein (MSP), a member of
      the plasminogen-related growth factor family. RON is mainly expressed in cells of
      epithelial origin and is required for embryonic development. In vitro RON
      activation results in epithelial cell dissociation, migration and matrix
      invasion, suggesting that RON might be involved in the pathogenesis of certain
      epithelial cancers in vivo. Indeed, recent studies have shown that RON expression
      is significantly altered in several primary human cancers, including those of the
      breast and colon. Truncation of the RON protein has also been found in primary
      tumors from the gastrointestinal tract. These alterations lead to constitutive
      activation of RON that causes cell transformation in vitro, induces neoplasm
      formation in athymic nude mice, and promotes tumor metastasis into the lung.
      Studies employing transgenic models further demonstrated that over-expression of
      RON in lung epithelial cells results in multiple tumor formation with features of
      large cell undifferentiated carcinoma. The oncogenic activities of RON are
      mediated by RON-transduced signals that promote unbalanced cell growth and
      transformation leading to tumor development. Thus, abnormal accumulation and
      activation of RON could play a critical role in vivo in the progression of
      certain malignant human epithelial cancers.

PMID- 12807734
TI  - Molecular mechanism for growth suppression of human hepatocellular carcinoma
      cells by acyclic retinoid.
AB  - We have reported previously that acyclic retinoid, a synthetic retinoid X
      receptor alpha (RXRalpha)-ligand, suppresses the development of hepatocellular
      carcinoma (HCC) in patients with chronic liver disease. On the other hand, HCCs
      become refractory to physiological concentrations of the natural RXRalpha-ligand,
      9-cis retinoic acid (9cRA), due to extracellular signal-regulated kinase (Erk)
      1/2-mediated phosphorylation and inactivation of RXRalpha. Here, we show that
      acyclic retinoid restores the function of RXRalpha in human HCC-derived HuH7
      cells by inactivating the Ras-Erk 1/2 signaling system, thereby dephosphorylating
      RXRalpha. In contrast, 9cRA failed to suppress phosphoErk 1/2 levels and
      subsequent RXRalpha phosphorylation. Although 9cRA also suppressed Ras activity,
      it simultaneously down-regulated mitogen-activated protein kinase phosphatase-1,
      an enzyme that inactivates Erk, thereby leaving the phosphorylation status of Erk
      unchanged. A combination of 9cRA (a potent ligand) and acyclic retinoid (a weak
      ligand preventing phosphorylation) resulted in a marked cooperation in
      transactivation via the RXR-response element and in inhibiting the proliferation
      of HuH7 cells. These events provide a novel molecular basis for the antitumor
      activity of acyclic retinoid against HCC.

PMID- 12807735
TI  - Aberrant Connexin 43 endocytosis by the carcinogen lindane involves activation of
      the ERK/mitogen-activated protein kinase pathway.
AB  - Although worldwide concerns have emerged about environmental factors that display
      carcinogenic and reprotoxic effects, little is known about the mechanism(s) by
      which these chemicals alter testicular function. Using the 42GPA9 Sertoli cell
      line, we recently reported that one widely used lipid-soluble pesticide, Lindane
      impairs gap junctional intercellular communication by promoting the intracellular
      localization of Connexin 43 (Cx43), a tumor suppressor. We showed here that this
      chemical triggered the accumulation of Cx43 within Rab5 positive endosomes.
      Interestingly, evidence is provided that Lindane-induced Cx43 endocytosis did not
      stem on alteration of Cx43 partition in lipid rafts. Lindane induced
      concomitantly Cx43 phosphorylation and activation of extracellular signal
      regulated kinases (ERK) but not of JNK and p38 mitogen- activated protein
      kinases. Inhibition of ERK pathway by PD98059, a MEK1-specific inhibitor,
      prevented Lindane-induced Cx43 phosphorylation, restored Cx43 membranous
      localization and gap junction coupling. Altogether, these findings provide the
      first evidence that Lindane-altered Cx43 endocytosis requires ERK activation.
      Such inappropriate activation of the mitogenic MAPK pathway and inactivation of
      the tumor suppressor Cx43 by Lindane may participate in the promotion of
      neoplastic cell growth.

PMID- 12807736
TI  - Cigarette smoke exposure increases ulcerative colitis-associated colonic adenoma
      formation in mice.
AB  - Both chronic ulcerative colitis and smoking are associated with colorectal cancer
      in humans. In the present study, we investigated the effects of cigarette smoke
      (CS) exposure on inflammation-associated tumorigenesis in the mouse colon. Male
      balb/c mice were allocated into six groups: control, CS (2%), CS (4%), colitis,
      colitis + CS (2%) and colitis + CS (4%). They were given water or 3% dextran
      sulfate sodium (DSS) in drinking water for 7 days to induce colitis, with or
      without 1 h daily exposure to 2 or 4% CS. They were then allowed to drink water
      for 14 days. The cycle of 7 day DSS +/- CS/14 day H2O treatments were repeated
      twice. Mice were killed immediately or 1 month after the three cycles of
      treatments. Results indicated colonic adenoma was only found in the colitis group
      (one out of 11), Colitis + CS (2%) group (seven out of 12) and colitis + CS (4%)
      group (four out of five) 1 month after three cycles of DSS and/or CS treatment.
      CS exposure dose-dependently increased adenoma formation in mice with inflamed
      mucosa. CS exposure plus colitis was strongly associated with a high incidence of
      dysplasia (P < 0.01) and adenocarcinoma formation (P < 0.01) compared with
      induction of colitis alone. Colitis induced cell proliferation and apoptosis in
      colonic tissues. Cigarette smoking significantly attenuated the apoptotic effect
      by DSS probably via the induction of anti-apoptotic protein bcl-2. The ratio of
      apoptosis over proliferation was also significantly lower in the colitis + CS
      groups. Vascular endothelial growth factor and angiogenesis in the colon were
      also increased by cigarette smoking in animals with colitis. In conclusion, CS
      promotes inflammation-associated adenoma/adenocarcinoma formation in the mouse
      colon in a dose-dependent manner. This tumor development is associated with the
      inhibition of cellular apoptosis and supported by increased angiogenesis.

PMID- 12807737
TI  - Dietary feeding of proanthocyanidins from grape seeds prevents
      photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and
      lipid peroxidation.
AB  - The use of dietary botanicals is receiving considerable interest in the
      protection of skin from the adverse biological effects of solar ultraviolet (UV)
      radiation. Dietary feeding of proanthocyanidins extracted from grape seeds (GSP)
      (0.2 and 0.5%, w/w) in AIN76 control diet to SKH-1 hairless mice resulted in
      prevention of photocarcinogenesis in terms of tumor incidence (20-95%), tumor
      multiplicity (46-95%) and tumor size (29-94%) against UVB-induced complete (both
      initiation + promotion), initiation and promotion stages of photocarcinogenesis.
      Feeding of GSP (0.5%, w/w) also resulted in prevention of malignant
      transformation of UVB-induced papillomas to carcinomas in terms of carcinoma
      incidence (45%), carcinoma multiplicity (61%) and carcinoma size (75%) compared
      with non-GSP treated mice following UVB-induced complete carcinogenesis protocol
      at the end of 30 weeks. Biochemical analysis revealed that treatment of GSP in
      vivo and in vitro systems significantly inhibited UVB- or Fe3+-induced lipid
      peroxidation by 57-66% (P<0.01) and 41-77% (P< 0.05-0.001), respectively, thus
      suggesting the antioxidant mechanism of photoprotection by GSP. Long-term feeding
      of GSP did not show apparent signs of toxicity in mice when determined in terms
      of body weight, diet consumption and physical characteristics of internal body
      organs like spleen, liver and kidney. Feeding of GSP also did not show apparent
      signs of toxicity when determined in terms of total body mass (mass of lean +
      fat), total bone mineral density and total bone mineral content by employing dual
      energy X-ray absorptiometry (DXA). DXA analysis also revealed that feeding of GSP
      significantly decreased tissue fat level (24-27%, P<0.05) without changing the
      total body mass of the animals compared with non-GSP-fed animals. This can be
      attributed to increased lipolysis or decreased synthesis of fat due to
      administration of GSP. Together, it can be suggested that inhibition of
      photocarcinogenesis by GSP treatment may be associated with the reduction in UVB
      induced oxidative damage and tissue fat content.

PMID- 12807738
TI  - Effect of resistant starch on genotoxin-induced apoptosis, colonic epithelium,
      and lumenal contents in rats.
AB  - The effect of different doses of a type-2 resistant starch (RS) in the form of
      high amylose cornstarch (HAS) on the intralumenal environment and the acute
      apoptotic response to a genotoxic carcinogen (AARGC) in the colon was assessed to
      determine if changes in lumenal conditions were associated with an enhanced
      apoptotic response to DNA damage. The control diet was a modified form of the AIN
      76 diet containing fully digestible starch but no dietary fibre. HAS was added to
      the control diet at the expense of digestible starch to give 10% HAS, 20% HAS and
      30% HAS. Rats were fed the different experimental diets for a period of 4 weeks,
      after which a single injection of azoxymethane was given to induce DNA damage in
      the colonic epithelium; 6 h later AARGC was measured. Other measures included
      fecal and cecal short chain fatty acids (SCFA) and pH, and cell proliferation in
      the colonic epithelium. In HAS-supplemented rats, fermentation events were
      significantly increased in both cecum and feces. There was a progressive decrease
      in pH in both the cecum and feces as the amount of HAS in the diet increased.
      SCFA concentrations, including butyrate, were significantly elevated by HAS with
      higher levels being observed in the cecum than in the feces. There was a
      significant increase in colonic AARGC with HAS doses of 20 and 30% (P < 0.01) but
      not with 10% HAS. Cell proliferation was not affected by any dose of HAS.
      Correlations with AARGC, independent of dietary group, were seen for fecal SCFAs
      and pH, suggesting that fermentation events, might explain the effect of RS on
      AARGC. Altering amounts of dietary RS changes fermentative activity in the colon.
      Increased RS is associated with enhanced AARGC. Changes in amount of fermentable
      substrate are capable of changing the biological response to DNA damage.

PMID- 12807739
TI  - Inherited defects in the DNA glycosylase MYH cause multiple colorectal adenoma
      and carcinoma.

PMID- 12807740
TI  - Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese
      population.
AB  - The objective was to study the relationship between cyclin D1 gene (CCND1)
      polymorphism and lung cancer in the Chinese population. Blood samples of 182
      cases and 185 controls were collected from a hospital based case-control study.
      PCR-SSCP was used to examine the G/A polymorphism in exon 4 of CCND1. The results
      showed that the frequencies of the CCND1 AA, GA and GG genotypes were 31.3, 46.7
      and 22.0% respectively in cases, and 21.1, 53.0 and 25.9 respectively in
      controls. Adjusted by age (in years), sex and smoking status, multivariate
      logistic regression analysis showed that the AA genotype was associated with a
      significantly increased risk (OR = 1.87, 95% CI 1.01-3.45) for lung cancer. In
      the stratification analysis, the CCND1 AA variant genotype was associated with
      increased risk in individuals who were </=50 years old (OR = 3.23, 95% CI 1.17
      8.96) and males (OR = 2.46, 95% CI 1.18-5.10). According to histological types,
      there was significantly higher frequency of AA genotype in squamous cell lung
      cancer than that in controls (OR = 2.92, 95% CI 1.07-8.03). In conclusion, it is
      suggested that the CCND1 G/A polymorphism is associated with the early onset of
      lung cancer in men and contributes to susceptibility to lung cancer, especially
      squamous cell cancer, in this population.

PMID- 12807741
TI  - Tissue factor signal transduction in angiogenesis.
AB  - Tissue factor (TF), a 47-kDa transmembrane glycoprotein, is a principal regulator
      of oncogenic neoangiogenesis and controls therefore the cancerous process.
      Although originally identified as a component of the coagulation cascade, it has
      become clear that TF functions as a cytokine-like receptor and this notion was
      confirmed by the discovery of coagulation-independent actions of TF (which
      include regulation of tumour growth, embryonic and oncogenic blood vessel
      formation as well as regulation of inflammation and sepsis). In accordance, TF
      mediated signal transduction events are readily detected and the elucidation of
      the underlying molecular mechanisms has recently seen spectacular progress and it
      is now understood that the role of TF in angiogenesis is both coagulation
      dependent and independent. The recent evidence for this emerging insight will be
      the subject of this review.

PMID- 12807742
TI  - Pre-cancerous lesions for colorectal cancers in rodents: a new concept.
AB  - It is widely believed that colorectal carcinogenesis is a representative multi
      step tumorigenesis with events of genetic alterations. Aberrant crypt foci (ACF)
      recognized on the surface of cancer-predisposed colons of rodents have been
      regarded as early-appearing pre-neoplastic lesions. However, it is not clear if
      such lesions are truly pre-cancerous lesions for colorectal cancers in rodents.
      Recently, beta-catenin-accumulated crypts (BCAC) were identified in colonic
      mucosa at the early stages of colon carcinogenesis. Accumulating evidence
      indicates that they are independent small dysplastic lesions of ACF. Here we
      discuss the importance of BCAC as pre-cancerous lesions in colon carcinogenesis.

PMID- 12807743
TI  - Potent iron chelators increase the mRNA levels of the universal cyclin-dependent
      kinase inhibitor p21(CIP1/WAF1), but paradoxically inhibit its translation: a
      potential mechanism of cell cycle dysregulation.
AB  - Iron (Fe) chelators are potential antitumor agents. Cellular Fe depletion results
      in a G1/S arrest but the precise molecular mechanisms involved remain unclear.
      Recent studies have shown that this process is complex with multiple cell cycle
      molecules being involved. We previously showed that Fe chelators such as 2
      hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) were far more potent
      antitumor agents than the clinically used ligand, desferrioxamine (DFO). To
      further characterize the effects of chelators on cell cycle arrest, we compared
      their activity with the DNA-damaging agents actinomycin D (Act D) and cisplatin
      (CP). These latter two compounds increase the expression of p53 and its target
      genes such as the universal cyclin-dependent kinase inhibitor, p21(CIP1/WAF1).
      Incubation of normal and neoplastic cells with all agents resulted in increased
      nuclear p53, the effect being pronounced for Act D and CP. As expected, both Act
      D and CP also markedly increased nuclear p21(CIP1/WAF1) protein levels, while DFO
      and 311 caused a significant (P<0.0004) decrease. This latter effect was
      surprising, as these chelators markedly increased mRNA levels of this molecule.
      Immunofluorescence studies showed that Act D and CP caused nuclear localization
      of p21(CIP1/WAF1). In contrast, the chelators prevented translation of
      p21(CIP1/WAF1). This did not appear to be due to a general effect of the
      chelators on preventing translation, as transferrin receptor 1 was markedly up
      regulated 15- to 21-fold by DFO and 311. Combination of 311 with Act D or CP
      prevented translation of p21(CIP1/WAF1) and its nuclear localization observed
      with these DNA-damaging agents. Significantly, the effect of chelation on
      reducing nuclear p21(CIP1/WAF1) was reversed by the Fe donor ferric ammonium
      citrate, indicating that p21(CIP1/WAF1) translation was dependent on
      intracellular Fe levels. This study demonstrates that while Fe chelators markedly
      up-regulate the mRNA levels of p21(CIP1/WAF1) they paradoxically inhibit
      translation.

PMID- 12807744
TI  - Hypoxia induces p53 through a pathway distinct from most DNA-damaging and stress
      inducing agents.
AB  - The p53 tumour suppressor gene is a transcription factor that can induce cell
      cycle arrest and apoptosis. In response to various stress-inducing signals, p53
      level increases and this is accompanied with increased activities of p53.
      Interestingly, the methylxanthine caffeine can abrogate the p53 accumulation
      induced by certain DNA-damaging agents by an unknown mechanism. In an effort to
      understand how different signals induce p53, human tumour cell lines were treated
      with combinations of various stress-inducing agents and caffeine. Caffeine
      inhibited the accumulation of p53 induced by leptomycin B (LMB), an inhibitor of
      CRM1, but not N-acetyl-leu-leu-norleucinal, a proteasome inhibitor. Furthermore,
      caffeine also inhibited the accumulation of p53 by a variety of stress-inducing
      agents in vivo, such as 5-fluorouracil, doxorubicin, mitomycin C, camptothecin
      and roscovitine. However, caffeine failed to affect the accumulation of p53 in
      hypoxia (HYP)-treated cells. These results suggested that HYP must use a distinct
      pathway from most DNA-damaging and stress-inducing agents to induce p53.

PMID- 12807745
TI  - Rat mammary carcinogenesis induced by in situ expression of constitutive Raf
      kinase activity is prevented by tethering Raf to the plasma membrane.
AB  - Mammary carcinogenesis induced through expression of activated Raf was
      investigated using a model in which retroviral vectors were infused into the
      central ducts of rat mammary glands. This model allows efficient expression of
      experimental proteins in a small fraction of endogenous mammary epithelial cells
      in situ. We previously reported that Raf is the dominant oncogenic signaling
      pathway from activated Ras in rat mammary glands. We show here that mammary gland
      carcinogenesis is rapidly induced by the expression of c-Raf-1 kinase that is
      activated by N-terminal truncation (Delta-Raf). Interestingly, targeting Raf to
      the plasma membrane via C-terminal fusion with Ras membrane localization signals
      (Raf-Caax) induces Raf kinase activity that transforms 3T3 cells more frequently
      than Delta-Raf, yet in situ expression of Raf-Caax does not induce mammary
      carcinomas. To investigate these contrasting results and begin elucidating the
      mechanisms of Raf-induced mammary carcinogenesis, we combined both activating
      mutations (N-terminal truncation and C-terminal membrane localization motifs) in
      one Raf construct (Delta-Raf-Caax). While Delta-Raf-Caax transforms 3T3 cells
      more efficiently than Delta-Raf or Raf-Caax, in situ expression of Delta-Raf-Caax
      does not induce carcinomas in vivo, demonstrating that lipid modification on the
      C-terminus of Delta-Raf negates its oncogenic potential in rat mammary gland.

PMID- 12807746
TI  - Aldehydic DNA lesions induced by catechol estrogens in calf thymus DNA.
AB  - The primary purpose of this research is to examine the hypothesis that reactive
      oxygen species generated by estrogen quinonoids are the main source for the
      formation of aldehydic DNA lesions (ADL) in genomic DNA. ADL induced by quinonoid
      metabolites of 17beta-estradiol (E2), e.g. 4-hydroxyestradiol (4-OH-E2), 2
      hydroxyestradiol (2-OH-E2), estrogen-3,4-quinones (E2-3,4-Q) and estrogen- 2,3
      quinone (E2-2,3-Q), were investigated in calf thymus DNA (CT-DNA) under
      physiological conditions. The abasic sites resulting from the spontaneous
      depurination-depyrimidination of the modified bases and the aldehydic base and
      sugar lesions resulting from the oxidative damage to deoxyribose moieties in the
      DNA molecules were measured by an aldehyde reactive probe and were estimated as
      the number of ADL per 106 nucleotides. With the addition of NADPH (100 micro M)
      and Cu(II) (20 micro M), nanomolar levels (100 nM) of 4-OH-E2 and 2-OH-E2 induced
      approximately 10-fold increases in the number of ADL over control (P<0.001). In
      parallel, increases in 8-oxoguanine were detected in DNA exposed to 4-OH-E2 and 2
      OH-E2 (100 nM) plus Cu(II) and NADPH. Further investigation indicated that the
      ADL induced by estrogen catechols plus Cu(II) and NADPH were causally involved in
      the formation of hydrogen peroxide and Cu(I). Both E2-2,3-Q and E2-3,4-Q alone
      induced a 2-fold increase in the number of ADL over control (P<0.05) in CT-DNA at
      high concentrations (1 mM). Neither neutral thermal hydrolysis nor lower ionic
      strength of the reaction medium induced further increases in the number of ADL in
      E2-3,4-Q-modified CT-DNA. Conversely, with the inclusion of Cu(II) and NADPH,
      both E2-3,4-Q and E2-2,3-Q (1 micro M) induced parallel formation of DNA single
      strand breaks and approximately 20-fold increases in the number of ADL over
      control (P < 0.001). The data also demonstrated that the ADL induced by estrogen
      quinones with and without the presence of Cu(II) and NADPH contain 69 and 78%
      putrescine-excisable ADL in CT-DNA, respectively. Additionally, results of the
      ADL cleavage assay indicate that the ADL induced by estrogen quinones plus Cu(II)
      and NADPH in CT-DNA were predominantly T7 exonuclease-excisable (50%) and
      exonuclease III- excisable (20%) ADL, whereas the intact ADL, and other ADL
      accounted for 5 and 25%, respectively. These results suggest that the ADL induced
      by estrogen quinones in CT-DNA are derived from oxidative events rather than
      depurination/depyrimidination of labile estrogen quinone-DNA adducts. Overall,
      our results are at variance with the idea that depurination of estrogen quinone
      DNA adducts is the major source for the formation of ADL in genomic DNA. We
      hypothesize that in addition to DNA adducts and oxidized bases, the ADL induced
      by estrogen quinonoid-mediated oxidative stress may play a role in estrogen
      induced carcinogenicity.

PMID- 12807747
TI  - Re: Lohrer,H.D., Hieber,L. and Zitzelsberger,H. (2002) Differential mutation
      frequency in mitochondrial DNA from thyroid tumours. Carcinogenesis, 23, 1577
      1582.

PMID- 12807748
TI  - Defining the function of XPC protein in psoralen and cisplatin-mediated DNA
      repair and mutagenesis.
AB  - DNA damage recognition plays an important role in DNA repair and mutagenesis.
      Failure to recognize DNA damage may lead to DNA replication without damage repair
      as well as mutation accumulation. Mutations can lead to many disease conditions.
      XPC is a DNA damage recognition protein that binds to damaged DNA templates at a
      very early stage during the DNA repair process. We have studied the role of the
      XPC protein in DNA cross-link reagents, psoralen and cisplatin, mediated DNA
      repair and mutagenesis. When psoralen and cisplatin-damaged plasmid DNA was
      transfected into xeroderma pigmentosum group C (XPC) cells, which were defective
      in the XPC gene, very distinct mutation frequency and spectrum was observed: a
      decreased mutation frequency for psoralen-damaged plasmid and an increased
      mutation frequency for cisplatin-damaged plasmid; in contrast, most mutations
      generated by psoralen in XPC cells were T-to-G transversions and most mutations
      generated by cisplatin in XPC cells were large deletions. We also determined the
      DNA repair ability of XPC cells by both host cell reactivation (HCR) assay and in
      vitro DNA repair assay. The HCR results showed greatly reduced host cell
      reactivation of a luciferase reporter for both psoralen and cisplatin-damaged
      plasmid DNA in XPC cells. The in vitro DNA repair results revealed a defective
      repair capacity for both psoralen and cisplatin-damaged plasmid DNA in nuclear
      extract prepared from XPC cells. However, this defective DNA repair activity was
      partially restored when a functional XPC protein was supplemented into the XPC
      nuclear extract prior to the reaction. These results suggest that the XPC protein
      DNA damage recognition function plays a crucial role in DNA repair initiation and
      mutation avoidance and XPC defects may lead to increased mutations and high risk
      for disease progression.

PMID- 12807749
TI  - Metallothionein deficiency enhances skin carcinogenesis induced by 7,12
      dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate in
      metallothionein-null mice.
AB  - To clarify the physiological role(s) of metallothionein (MT) in carcinogenesis,
      we studied the susceptibility of MT-null mice to chemically mediated
      carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced two-stage carcinogenesis model. The
      MT-null mice were subjected to a single topical application of DMBA (50 or 100
      micro g/mouse) and, 1 week later, to promotion with TPA (10 micro g/mouse) twice
      a week for 20 weeks. At week 21, nearly all of the MT-null mice developed tumors
      in the skin, in contrast to only 10-40% of wild-type mice. No tumors were
      observed in MT-null or wild-type mice that were administered TPA alone. By using
      the PCR-restriction fragment length polymorphism and PCR-single strand
      conformation polymorphism methods, we found a transversion of A182 to T in codon
      61 of c-Ha-ras in the papilloma tissue of MT-null mice and wild-type mice but
      failed to find any mutations in the c-Ki-ras and c-N-ras genes. In two-stage skin
      carcinogenesis induction by DMBA/TPA, p53 and p21(WAF1/Cip1) expression levels
      were found to be increased in MT-null mice compared with wild-type mice. As to an
      earlier change at the promotion stage triggered by TPA application, MT-null mice
      were found to have both hyperplasia of the epithelium and a marked degree of
      inflammation in the basal layer, indicating that the induced as well as
      endogenous MT acted as a protective factor against tumorigenesis. In conclusion,
      the present study has demonstrated that MT has antitumorigenic potential in both
      the initiation and promotion stages of the two-stage chemical skin carcinogenesis
      model.

PMID- 12807750
TI  - Prevention of dual promoting effects of pentachlorophenol, an environmental
      pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in
      mice by green tea infusion.
AB  - In order to explore a possibility that the custom of drinking green tea infusion
      is efficacious for reducing the carcinogenic risk of environmental exposure to
      pentachlorophenol (PCP), we examined the effects in a hepato- and
      cholangiocarcinogenesis model in mice exposed to diethylnitrosamine (DEN). In the
      first experiment, groups of 15 male mice were initially treated with DEN at a
      dose of 20 p.p.m. in the drinking water for the first 8 weeks followed by a 4
      week recovery interval by PCP at concentrations of 0 (basal diet), 300 or 600
      p.p.m. in the diet for 23 weeks. Further groups of animals were treated with DEN
      and PCP in the same manner and received 2% green tea infusion (GT) instead of the
      drinking water from week 10 until death. PCP exposure at the high dose promoted
      DEN-induced hepatocarcinogenesis, and also caused progression of cystic
      hyperplasias of the intrahepatic bile ducts to cholangiocellular tumors. Co
      administration of GT was able to prevent the increases of incidences and
      multiplicities of DEN-induced hepatocellular tumors and also arrest the
      progression of cholangiocellular tumors. In the second experiment, co-treatment
      with GT in the drinking water from 1 week before 300 or 600 p.p.m. PCP treatment
      in the diet to the end of the experiment at week 3 in B6C3F1 male mice suppressed
      increases of serum ALT activities, 8-oxodeoxyguanosine levels in liver DNA and
      bromodeoxyuridine labeling indices of hepatocytes and intrahepatic biliary
      epithelial cells induced by PCP. These findings suggest that regular intake of
      green tea may reduce the carcinogenic risk posed by an environmental pollutant,
      PCP, presumably due to effects on oxidative stress.

PMID- 12807751
TI  - Genetic effects on urinary 1-hydroxypyrene levels in a Korean population.
AB  - Urinary 1-hydroxypyrene (1-OHP) has been used as a biomarker for assessing the
      level of exposure to environmental carcinogenic polycyclic aromatic hydrocarbons
      (PAHs). In order to perform the appropriate biological monitoring for examining
      the level of exposure to PAHs, this study investigated whether or not genetic
      polymorphisms of the metabolic enzymes, which might be involved in the metabolism
      of pyrene, affected the urinary 1-OHP levels in a population of 661 Koreans
      (male, 63%; female, 37%; mean age, 36.5 +/- 11.1 years) who were not
      occupationally exposed to PAHs. Urinary 1-OHP was detected in 76% of the subjects
      (range 0.001-3.8 micro g/l). Among the physical and lifestyle factors, cigarette
      smoking was found to be associated with the urinary 1-OHP levels (P < 0.05).
      After adjusting for these factors, we found that the GSTT1 genotypes affected the
      urinary 1-OHP levels, i.e. the GSTT1 present subjects had approximately 1.5 times
      the urinary 1-OHP level than the GSTT1 null subjects (P < 0.05). In the case of
      the subjects who were also GSTM1 null, this trend became stronger, i.e. the GSTT1
      present subjects had approximately 2 times the urinary 1-OHP level (P < 0.01).
      However, the genetic polymorphism of the other metabolic enzymes, cytochrome P
      450 (CYP)1A1, CYP1B1 and GSTM1 alone, did not affect the urinary 1-OHP level.
      Therefore, this study suggests that the GSTT1 genetic polymorphism has the
      potential to affect the biological monitoring of PAHs with urinary 1-OHP, and
      might act as a genetic factor in PAH-related toxicity.

PMID- 12807752
TI  - Sphingolipids suppress preneoplastic rat hepatocytes in vitro and in vivo.
AB  - Sphingolipids can modulate cell growth, differentiation and apoptosis. In the
      present investigation, selective death of hepatocytes localized in enzyme-altered
      foci (EAF hepatocytes) was shown to be induced by sphingolipids. Sphingosine (20
      micro M) caused rapid cell death predominantly of EAF hepatocytes in vitro.
      During 4 h of such exposure, cytochrome c was released from the mitochondria into
      the cytoplasm and the number of cells demonstrating cleaved caspase-9 activity
      increased. The selective sensitivity of EAF cells to sphingolipid-induced death
      was attenuated by tumor necrosis factor-alpha. In previous studies we have
      demonstrated that EAF hepatocytes are resistant to Fas-mediated apoptosis, a
      resistance shown here to be reversed by low concentrations of sphingosine.
      Immunohistological staining revealed higher levels of glucosylated ceramide in
      EAF than in the surrounding tissue. Furthermore, an inhibitor of glucosylation
      enhanced the toxicity of ceramide towards EAF cells. TLC analysis suggested low
      levels of sphingosine in preneoplastic lesions. In in vivo experiments EAF
      bearing rats were fed a diet supplemented with 0.1% sphingomyelin for 2 weeks.
      Sphingolipid feeding reduced the number of EAF and EAF area in the liver by 40
      50% as compared with rats fed a control diet. These studies indicate that the
      turnover of sphingolipids in preneoplastic EAF hepatocytes is altered. This
      alteration may explain not only the increased sensitivity of EAF cells towards
      sphingolipid-induced cell death, but also the resistance of these hepatocytes to
      cell death involving sphingolipids as second messengers. Furthermore,
      sphingomyelin in the diet may prevent EAF development. It is suggested that the
      altered turnover of sphingolipids might be a target for chemoprevention of
      hepatocellular carcinoma.

PMID- 12807753
TI  - Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations
      caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells
      in vivo.
AB  - 8-Hydroxyguanine (8OHG), an oxidatively damaged base, and benzo[a]pyrene-diol
      epoxide (BPDE), a metabolite of benzo[a]pyrene found in cigarette smoke, are
      thought to be major causes for G:C to T:A transversions in DNA of human cells. In
      this study, we assessed the abilities of OGG1, MYH and APE1 proteins, which are
      components of a base excision repair pathway, to suppress G:C to T:A
      transversions caused by 8OHG or BPDE by a bacterial suppressor tRNA (supF)
      forward mutation assay using a shuttle plasmid, pMY189. The introduction of a
      single 8OHG residue at position 159 of the supF gene and treatment with BPDE led
      to a 65- and 34-fold increase in mutation frequencies of the pMY189 plasmid,
      respectively, after replication in the NCI-H1299 human lung cancer cell line. G:C
      to T:A transversions were predominantly induced in these plasmids. Both the
      mutation frequency of the 8OHG-containing plasmid in NCI-H1299 cells and the
      occurrence of G:C to T:A transversions at position 159 in the supF gene were
      significantly reduced by overexpression of OGG1 and MYH proteins, but not by that
      of APE1 protein. In contrast, neither mutation frequency nor the occurrence of
      G:C to T:A transversion of the BPDE-treated plasmid was reduced by overexpression
      of OGG1, MYH and APE1 proteins. These results indicate that OGG1 and MYH function
      as suppressors for G:C to T:A transversions by 8OHG but not by BPDE in human
      cells.

PMID- 12807754
TI  - Roles of p38- and c-jun NH2-terminal kinase-mediated pathways in 2
      methoxyestradiol-induced p53 induction and apoptosis.
AB  - As 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, has been
      established to cause apoptosis of prostate cancer cells, the downstream effectors
      of the signaling remain unclear. In the current study, we investigated molecular
      mechanisms by which 2-ME induces apoptosis in human prostate cancer cell line,
      LNCaP. It was found that 2-ME mediates apoptosis through p53 induction. Nuclear
      factor kappaB (NFkappaB) was activated by 2-ME and closely regulated by the
      mitogen-activated protein kinase, p38. Inhibition of p38 or NFkappaB resulted in
      suppression of p53 induction and apoptosis. Moreover, we demonstrated that 2-ME
      activates the c-jun NH2-terminal kinase (JNK)/activation protein (AP)-1 pathway.
      Interestingly, inhibition of JNK strongly reduced Bcl-2 phosphorylation by 2-ME
      as well as p53 induction, and almost completely suppressed 2-ME-induced
      apoptosis. Androgen stimulation with dihydrotestosterone, a major endogenous
      metabolite of testosterone, also significantly inhibited p38/NFkappaB and JNK/AP
      1 activation and apoptosis. The results suggest that not only p53 induction
      through p38/JNK-dependent NFkappaB/AP-1 activation but also JNK-dependent Bcl-2
      phosphorylation are required for 2-ME-induced apoptosis; moreover, inhibition of
      these pathways may be involved in androgen-mediated resistance to apoptosis.

PMID- 12807755
TI  - Vitamin D receptor start codon polymorphism and colorectal cancer risk: effect
      modification by dietary calcium and fat in Singapore Chinese.
AB  - Vitamin D has been implicated as a protective agent against colorectal cancer. We
      hypothesized that a functional start codon polymorphism in the vitamin D receptor
      (VDR) influences the risk of colorectal carcinoma. We conducted a case-control
      study nested within a large cohort of Singapore Chinese. VDR genotypes,
      determined by FokI restriction endonuclease digestion of PCR-amplified DNA, were
      performed on 217 colorectal cancer cases and 890 controls. We found that compared
      with individuals carrying the FF genotype, those with Ff genotype had a 51%
      increase in risk of colorectal cancer and those with the ff genotype, an 84%
      increase in risk (P for trend = 0.01). The effect of the VDR genotype on risk
      appeared to be modified by both dietary calcium and fat. Among those with either
      low calcium or low fat intake (below the median values in controls), the risk for
      colorectal cancer increased in a gene-dose-dependent manner such that individuals
      possessing the ff genotype displayed an approximately 2.5-fold increased risk
      that was statistically significant. There was little evidence of a VDR genotype
      colorectal cancer association among subjects with higher than median values of
      either dietary fat or calcium.

PMID- 12807756
TI  - Erythropoietin regulates tumour growth of human malignancies.
AB  - In addition to the chief function of erythropoietin (Epo) in promoting
      erythropoiesis, some other roles have been found in the brain and uterus. We have
      reported that signalling pathways of Epo and Epo receptor (EpoR) are involved in
      the tumourigenesis of ovarian and uterine cancers. To determine whether Epo plays
      a similar role in other malignancies, we studied the expression of Epo in several
      malignant human cell lines. We found that 24 malignant human cell lines examined
      express Epo and EpoR regardless of their origins, types, genetic characteristics
      and biological properties and secrete a very small amount of Epo individually and
      that most of them respond to hypoxic stimuli by enhanced secretion of Epo. To
      determine whether the Epo-EpoR pathway operates in tumours of these cell lines,
      we transplanted several cell lines into nude mice and confirmed the presence of
      Epo-responsive sites in xenografts in which the phosphorylation of the STAT5
      (signal transducer and activator of transcription) is detectable. Furthermore, in
      nude mice we blocked the Epo signalling in xenografts of two representative cell
      lines, stomach choriocarcinoma and melanoma, by i.p. injections of EpoR
      antagonist and found inhibition of angiogenesis and survival of tumour cells
      leading to destruction of tumour masses and disturbances of phosphorylation of
      STAT5. In contrast, Epo mimetic peptide promotes angiogenesis and tumour cell
      survival. These findings suggest that Epo is indispensable for the growth and
      viability of malignant tumour and also that the deprivation of Epo signalling may
      be a promising therapy for human malignancy.

PMID- 12807757
TI  - Modulation of benzo[a]pyrene-induced p53 DNA activity by acrolein.
AB  - Acrolein, a highly electrophilic alpha,beta-unsaturated aldehyde, is by far the
      most reactive amongst the aldehydes present in smoke. The relative contribution
      of acrolein to complex mixture toxicity of smoke at the molecular level remains
      unknown. The current study examines the ability of acrolein to modulate the
      effect of benzo[a]pyrene (B[a]P), a major carcinogen found in smoke, on p53.
      Exposure of human lung adenocarcinoma A549 cells to 1 mM B[a]P for 48 h strongly
      activated the expression of p53 as seen by western blotting, and its DNA binding
      as shown by an electrophoretic mobility shift assay. Treatment of A549 cells with
      a non-lethal dose of acrolein alone (50 fmol/cell for 0.5 h) depleted 80% of
      total cellular glutathione but had no effect on basal p53 protein levels. When
      B[a]P-treated cells (48 h) were exposed to acrolein for 0.5 h there was also no
      effect on B[a]P-induced p53 protein levels. However, acrolein treatments
      profoundly inhibited the DNA binding of p53 under both basal and B[a]P-induced
      conditions. Depleting glutathione with buthionine sulfoximine in B[a]P-treated
      cells to levels similar to those obtained with acrolein decreased p53 DNA binding
      substantially less than with acrolein. Using a p53 dual luciferase reporter
      assay, acrolein caused an 83% decrease in the p53 activity induced by B[a]P (1 mM
      for 24 h post-transfection). The p53 protein that was immunoprecipitated after
      acrolein treatment was reactive with an anti-acrolein antibody indicating
      covalent modification. Results from this study suggest that acrolein can inhibit
      p53 DNA binding and activity by direct covalent modification as well as
      alteration of intracellular redox status. As both acrolein and B[a]P are found in
      cigarette smoke, this type of interaction may play an important role in the
      initiation of lung cancer by altering the tumor suppressor activity of p53.

PMID- 12807758
TI  - Inactivation of DNA repair gene O6-methylguanine-DNA methyltransferase by
      promoter hypermethylation and its relation to p53 mutations in esophageal
      squamous cell carcinoma.
AB  - The development of esophageal squamous cell carcinoma (ESCC) has been linked to
      exposure to carcinogens such as nitrosamines that cause various alkyl DNA damages
      and O6-methylguanine-DNA methyltransferase (MGMT) is a primary defence against
      alkylation-induced mutagenesis and carcinogenesis. This study was to investigate
      the role of inactivation of MGMT by promoter hypermethylation and its relation to
      p53 mutations in ESCC. Methylation of MGMT promoter was determined by methylation
      specific polymerase chain reaction in 119 ESCC specimens, 22 corresponding tissue
      samples adjacent to the tumors, and 21 normal epithelial specimens of the
      esophagus. The levels of MGMT protein in ESCC with methylated or unmethylated
      MGMT were analyzed by quantitative immunohistochemistry. Mutations of p53 in 119
      ESCC were detected by denaturing high-performance liquid chromatography and
      sequencing. We found that all 21 normal esophageal tissues had unmethylated MGMT;
      however, among 119 ESCC, 46 (38.7%) had hypermethylated MGMT. This epigenetic
      change also occurred in some normal tissues adjacent to the tumors. The level of
      MGMT protein in MGMT-methylated ESCC was significantly lower than that in MGMT
      unmethylated ESCC, whereas great inter-individual variation and poor expression
      was also observed among MGMT-unmethylated ESCC. Fifty-one percent (61/119) ESCC
      showed p53 mutations but the distribution of the mutations did not differ
      significantly between MGMT-methylated ESCC (44%) and MGMT-unmethylated ESCC
      (56.2%; P = 0.18). MGMT promoter hypermethylation was neither associated with
      overall G:C to A:T mutations nor associated with this type of mutations in non
      CpG dinucleotides in p53. Our results demonstrate that inactivation of MGMT by
      aberrant promoter methylation is a frequent molecular event in ESCC. This
      epigenetic alteration is an important, but may not be the sole, mechanism leading
      to the impaired expression of MGMT. Aberrant MGMT methylation seemed not to be
      associated with overall frequency and spectrum of p53 mutations in ESCC.

PMID- 12807759
TI  - Sex difference in the proliferative response of mouse hepatocytes to treatment
      with the CAR ligand, TCPOBOP.
AB  - The nuclear receptor Constitutive Androstane Receptor (CAR) binds DNA as a
      heterodimer with the retinoic-X receptor and activates gene transcription.
      Previously, in vitro studies have shown that the testosterone metabolites,
      androstenol and androstenol, inhibit the constitutive transcriptional activity of
      CAR, suggesting that differences might exist in the response to CAR-mediated gene
      activation between different sexes. In this study, we have analyzed the response
      of female and male CD-1 mice to stimulation of hepatocyte proliferation caused by
      the CAR ligand TCPOBOP. Results showed that the labelling index of female
      hepatocytes at 24, 30 and 36 h after treatment was much higher than that found in
      males. The higher proliferative activity of female hepatocytes was associated
      with increased hepatic levels of cyclin D1, cyclin A, E2F and enhanced
      phosphorylation of pRb and p107. The increased mitogenic response of females was
      associated with higher mRNA levels of CYP2B10, a known target of CAR.
      Administration of androstenol to TCPOBOP-treated mice caused a reduction of
      labelling index, which was accompanied by a decrease of CYP2B10 and CAR mRNA
      levels. In conclusion, the results show that, in addition to microsomal
      detoxification, another biological response elicited by the CAR ligand TCPOBOP,
      namely, hepatocyte proliferation, occurs at higher levels in female than male
      mice, suggesting that CAR transcriptional activity in males is partially
      counteracted by physiological higher levels of testosterone metabolites such as
      androstenol and androstenol.

PMID- 12807760
TI  - Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy
      subjects.
AB  - Gene-environment interactions play an important role in folate metabolism, with a
      potential impact on human health. Deficiencies in the uptake of key
      micronutrients and variant genotypes can affect the folic acid cycle, modulating
      methyl group transfer in key processes and leading to increased cancer risk and
      Down syndrome incidence. So far, the significance of folate status and metabolic
      genotypes on baseline levels of DNA damage in normal individuals has not been
      fully elucidated. In this study, the possible modulation of SCE, micronuclei and
      tail moment values in peripheral lymphocytes by plasma levels of folic acid,
      homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase
      (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was
      investigated in 191 healthy subjects. The results obtained show a highly
      significant (P = 0.001) positive association between plasma levels of vitamin B12
      and frequencies of both SCE and high frequency cells (HFC, above 90 degrees
      percentile) in smokers. No significant effect was observed in non-smokers.
      Moreover, after correction for age, gender and GSTM1 genotype, a significant
      association (P = 0.026) between the MTRR 66GG variant genotype and higher
      micronucleus rates was observed. Tail moment values were not affected by any of
      the independent variables considered. Overall, the results obtained suggest that
      both folate status and relevant metabolic genotype can influence background
      levels of DNA damage in normal subjects. The significant association observed in
      smokers between plasma vitamin B12 and SCE frequencies may highlight the effect
      of methylation status on DNA damage and repair, although the role of other,
      unidentified dietary factors cannot be ruled out. At the same time, micronucleus
      data indicate that the MTRR 66GG variant may represent another individual trait
      of relative genomic instability, thus supporting epidemiological data on
      increased risk of Down syndrome conception in MTRR 66GG subjects.

PMID- 12807761
TI  - Outbred CD-1 mice carry the susceptibility allele at the pulmonary adenoma
      susceptibility 1 (Pas1) locus.
AB  - CD-1 is the outbred mouse line most often used in toxicology and carcinogenicity
      bioassays. A literature survey revealed a relatively high (21.8%) incidence of
      spontaneous lung tumors in these mice, and a susceptibility to lung tumorigenesis
      induced by vinyl chloride, styrene or benzene inhalation that is not seen in
      B6C3F1 or C57BL/6 mice, or in rats and hamsters. As the pulmonary adenoma
      susceptibility 1 (Pas1) locus is the major determinant of genetic susceptibility
      to lung tumorigenesis in mice, we analyzed CD-1 mice for genetic polymorphisms of
      the Kras2 and Pthlh genes, which are tightly linked with the Pas1 locus. From 95
      to 98% of CD-1 mice carried the susceptibility allele at the Pas1 locus either at
      homozygosity or heterozygosity, providing a molecular genetic explanation for the
      high susceptibility of CD-1 mice to spontaneous and chemically induced lung
      tumorigenesis. These results may have implications for the risk assessment of
      chemicals in humans using experimental animals that display strain-specific lung
      tumorigenicity.

PMID- 12807762
TI  - Recovery of gap junctional intercellular communication after phorbol ester
      treatment requires proteasomal degradation of protein kinase C.
AB  - Reversible down-regulation of gap junctional intercellular communication (GJIC)
      is proposed to be an important cellular mechanism in tumor promotion. Gap
      junction function is modified by a variety of tumor promoters, including the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of cells with
      TPA results in the activation and subsequent depletion of the TPA-responsive
      protein kinase C (PKC) isoforms. TPA-induced degradation of the PKC isoforms
      alpha, delta and epsilon was recently shown to occur via the ubiquitin-proteasome
      pathway. In the present study we investigated the role of the proteasome in the
      TPA-induced modification of GJIC in IAR20 rat liver epithelial cells. TPA
      exposure of IAR20 cells induced hyperphosphorylation of gap junction protein
      connexin43 and inhibition of GJIC. Prolonged TPA treatment induced down
      regulation of PKCalpha, delta and epsilon and a reduction in the total PKC
      activity, which was associated with recovery of GJIC. Co-treatment of IAR20 cells
      with TPA and the proteasomal inhibitor MG132 suppressed down-regulation of
      PKCalpha, delta and epsilon and caused prolonged PKC activity. Under these
      conditions, the recovery of GJIC was blocked. The general PKC inhibitor GF109203X
      reversed the effect of MG132, indicating that the prolonged TPA-induced
      inhibition of GJIC caused by MG132 was due to the prolonged PKC activity. These
      results indicate that proteasomal degradation of PKC is one mechanism by which
      the recovery of GJIC after TPA treatment is regulated.

PMID- 12807763
TI  - Alterations in signal transduction pathways implicated in tumour progression
      during multistage mouse skin carcinogenesis.
AB  - The multistage mouse skin carcinogenesis model, although an artificial one, is an
      ideal system to study the timing of qualitative and quantitative alterations
      which take place during the different stages of chemical carcinogenesis, allowing
      analysis of the events that lead to the transition from the stage of initiation
      to the stage of promotion and finally to the progression of carcinogenesis. In
      this review we focus on the role of the H-ras gene and its target molecules
      during mouse skin carcinogenesis. Besides H-ras, which is a critical target of
      chemical carcinogens, we report alterations in oncosuppressor genes. Finally, we
      examine the potential suppression of metastatic dynamics of spindle cells after
      biological or chemical inhibition of the signalling cascades involved in mouse
      skin carcinogenesis.

PMID- 12807764
TI  - C. B. Bridges' repeat hypothesis and the nature of the gene.

PMID- 12807765
TI  - Phospholipase C-gamma contains introns shared by src homology 2 domains in many
      unrelated proteins.
AB  - Many proteins with novel functions were created by exon shuffling around the time
      of the metazoan radiation. Phospholipase C-gamma (PLC-gamma) is typical of
      proteins that appeared at this time, containing several different modules that
      probably originated elsewhere. To gain insight into both PLC-gamma evolution and
      structure-function relationships within the Drosophila PLC-gamma encoded by small
      wing (sl), we cloned and sequenced the PLC-gamma homologs from Drosophila
      pseudoobscura and D. virilis and compared their gene structure and predicted
      amino acid sequences with PLC-gamma homologs in other animals. PLC-gamma has been
      well conserved throughout, although structural differences suggest that the role
      of tyrosine phosphorylation in enzyme activation differs between vertebrates and
      invertebrates. Comparison of intron positions demonstrates that extensive intron
      loss has occurred during invertebrate evolution and also reveals the presence of
      conserved introns in both the N- and C-terminal PLC-gamma SH2 domains that are
      present in SH2 domains in many other genes. These and other conserved SH2 introns
      suggest that the SH2 domains in PLC-gamma are derived from an ancestral domain
      that was shuffled not only into PLC-gamma, but also into many other unrelated
      genes during animal evolution.

PMID- 12807766
TI  - Delineating the requirements for spontaneous DNA damage resistance pathways in
      genome maintenance and viability in Saccharomyces cerevisiae.
AB  - Cellular metabolic processes constantly generate reactive species that damage
      DNA. To counteract this relentless assault, cells have developed multiple
      pathways to resist damage. The base excision repair (BER) and nucleotide excision
      repair (NER) pathways remove damage whereas the recombination (REC) and
      postreplication repair (PRR) pathways bypass the damage, allowing deferred
      removal. Genetic studies in yeast indicate that these pathways can process a
      common spontaneous lesion(s), with mutational inactivation of any pathway
      increasing the burden on the remaining pathways. In this study, we examine the
      consequences of simultaneously compromising three or more of these pathways.
      Although the presence of a functional BER pathway alone is able to support
      haploid growth, retention of the NER, REC, or PRR pathway alone is not,
      indicating that BER is the key damage resistance pathway in yeast and may be
      responsible for the removal of the majority of either spontaneous DNA damage or
      specifically those lesions that are potentially lethal. In the diploid state,
      functional BER, NER, or REC alone can support growth, while PRR alone is
      insufficient for growth. In diploids, the presence of PRR alone may confer a
      lethal mutation load or, alternatively, PRR alone may be insufficient to deal
      with potentially lethal, replication-blocking lesions.

PMID- 12807767
TI  - Repair of damaged and mismatched DNA by the XPC homologues Rhp41 and Rhp42 of
      fission yeast.
AB  - Rhp41 and Rhp42 of Schizosaccharomyces pombe are homologues of human XPC, which
      is involved in nucleotide excision repair (NER) of damaged DNA. Inactivation of
      rhp41 caused moderate sensitivity to ultraviolet (UV) radiation. In addition, an
      increase of mitotic mutation rates was observed in the rhp41 mutant, which was
      dependent on active translesion polymerase Z. UV sensitivity and mutation rates
      were not different between rhp42 and wild type, but compared to rhp41 were
      further increased in rhp41 rhp42 cells. Transcription of the fbp1 gene (induced
      in vegetative cells) and of the SPBC1289.14 gene (induced during meiosis) was
      strongly blocked by UV-induced damages in the rhp41 mutant, but not, or only
      slightly, reduced in rhp42 background. NER-dependent short-patch repair of
      mismatches formed during meiosis was slightly affected in rhp41, moderately
      affected in rhp42, and absent in rhp41 rhp42. Epistasis analysis with rhp7 and
      rhp26 indicates that Rhp41 and Rhp42 are both involved in the global genome and
      transcription-coupled repair subpathways of NER. Rhp41 plays a major role in
      damage repair and Rhp42 in mismatch repair.

PMID- 12807768
TI  - Opposite roles of the F-box protein Rcy1p and the GTPase-activating protein Gyp2p
      during recycling of internalized proteins in yeast.
AB  - The F-box protein Rcy1p is part of a non-SCF (Skp1p-cullin-F-box protein) complex
      involved in recycling of internalized material. Like rcy1Delta, cells lacking the
      Rab-GTPase Ypt6p or its heterodimeric GEFs Rgp1p and Ric1p are unable to recycle
      the v-SNARE Snc1p. Here we provide genetic evidence suggesting that Rcy1p is a
      positive regulator of Ypt6p. Deletion of the GAP Gyp2p restores recycling in
      rcy1Delta, while overexpression of an active form of Ypt6p partially suppresses
      the recycling defect of rcy1Delta cells. Conversely, overexpression of Gyp2p in
      wild-type cells interferes with recycling of GFP-Snc1p, and the cells accumulate
      membrane structures as evidenced by electron microscopy. Gyp2p-GFP is distributed
      throughout the cytoplasm and accumulates in punctate structures, which
      concentrate in an actin-dependent manner at sites of polarized growth. Taken
      together, our results suggest that the F-box protein Rcy1p may activate the Ypt6p
      GTPase module during recycling.

PMID- 12807769
TI  - Sex slows down the accumulation of deleterious mutations in the homothallic
      fungus Aspergillus nidulans.
AB  - Coexistence of sexual and asexual reproduction within the same individual is an
      intriguing problem, especially when it concerns homothallic haplonts, like the
      fungus Aspergillus nidulans. In this fungus asexual and sexual offspring have
      largely identical genotypes. This genetic model organism is an ideal tool to
      measure possible fitness effects of sex (compared to asex) resulting from causes
      other than recombination. In this article we show that slightly deleterious
      mutations accumulate at a lower rate in the sexual pathway than in the asexual
      pathway. This secondary sex advantage may contribute to the persistence of sexual
      spores in this fungus. We propose that this advantage results from intra
      organismal selection of the fittest gametes or zygotes, which is more stringent
      in the costly sexual pathway.

PMID- 12807770
TI  - The G-protein alpha-subunit GasC plays a major role in germination in the
      dimorphic fungus Penicillium marneffei.
AB  - The opportunistic human pathogen Penicillium marneffei exhibits a temperature
      dependent dimorphic switch. At 25 degrees, multinucleate, septate hyphae that can
      undergo differentiation to produce asexual spores (conidia) are produced. At 37
      degrees hyphae undergo arthroconidiation to produce uninucleate yeast cells that
      divide by fission. This work describes the cloning of the P. marneffei gasC gene
      encoding a G-protein alpha-subunit that shows high homology to members of the
      class III fungal Galpha-subunits. Characterization of a DeltagasC mutant and
      strains carrying a dominant-activating gasC(G45R) or a dominant-interfering
      gasC(G207R) allele show that GasC is a crucial regulator of germination. A
      DeltagasC mutant is severely delayed in germination, whereas strains carrying a
      dominant-activating gasC(G45R) allele show a significantly accelerated
      germination rate. Additionally, GasC signaling positively affects the production
      of the red pigment by P. marneffei at 25 degrees and negatively affects the onset
      of conidiation and the conidial yield, showing that GasC function overlaps with
      functions of the previously described Galpha-subunit GasA. In contrast to the S.
      cerevisiae ortholog Gpa2, our data indicate that GasC is not involved in carbon
      or nitrogen source sensing and plays no major role in either hyphal or yeast
      growth or in the switch between these two forms.

PMID- 12807771
TI  - COM, a heterochromatic locus governing the control of independent endogenous
      retroviruses from Drosophila melanogaster.
AB  - ZAM and Idefix are two endogenous retroviruses whose expression is tightly
      controlled in Drosophila melanogaster. However, a line exists in which this
      control has been perturbed, resulting in a high mobilization rate for both
      retroviruses. This line is called the U (unstable) line as opposed to the other S
      (stable) lines. In the process of analyzing this control and tracing the genetic
      determinant involved, we found that ZAM and Idefix expression responded to two
      types of controls: one restricting their expression to specific somatic cells in
      the ovaries and the other silencing their expression in S lines but permitting it
      in U lines. While studying this second control in the U or S backgrounds, we
      found that the heterochromatic locus 20A2-3 on the X chromosome, previously
      implicated in the regulation of a third retroelement, gypsy, also controlled both
      ZAM and Idefix. We report here that genetic determinants necessary for endogenous
      retrovirus silencing occur at the 20A2-3 locus, which we call COM, for centre
      organisateur de mobilisation. We propose that if this point of control becomes
      mutated during the life of the fly, it may trigger processes reactivating dormant
      endogenous retroviruses and thus bring about sudden bursts of mobilization.

PMID- 12807772
TI  - Dynamics of molecular markers linked to the resistance loci in a mosquito
      Plasmodium system.
AB  - Models on the evolution of resistance to parasitism generally assume fitness
      tradeoffs between the costs of being parasitized and the costs associated with
      resistance. This study tested this assumption using the yellow fever mosquito
      Aedes aegypti and malaria parasite Plasmodium gallinaceum system. Experimental
      mosquito populations were created by mixing susceptible and resistant strains in
      equal proportions, and then the dynamics of markers linked to loci for Plasmodium
      resistance and other unlinked neutral markers were determined over 12
      generations. We found that when the mixed population was maintained under
      parasite-free conditions, the frequencies of alleles specific to the susceptible
      strain at markers closely linked to the loci for resistance (QTL markers) as well
      as other unlinked markers increased significantly in the first generation and
      then fluctuated around equilibrium frequencies for all six markers. However, when
      the mixed population was exposed to an infected blood meal every generation,
      allele frequencies at the QTL markers for resistance were not significantly
      changed. Small population size caused significant random fluctuations of allele
      frequencies at all marker loci. Consistent allele frequency changes in the QTL
      markers and other unlinked markers suggest that the reduced fitness in the
      resistant population has a genome-wide effect on the genetic makeup of the mixed
      population. Continuous exposure to parasites promoted the maintenance of alleles
      from the resistant Moyo-R strain in the mixed population. The results are
      discussed in relation to the proposed malaria control strategy through genetic
      disruption of vector competence.

PMID- 12807773
TI  - Gene silencing triggered by non-LTR retrotransposons in the female germline of
      Drosophila melanogaster.
AB  - Several studies have recently shown that the activity of some eukaryotic
      transposable elements is sensitive to the presence of homologous transgenes,
      suggesting the involvement of homology-dependent gene-silencing mechanisms in
      their regulation. Here we provide data indicating that two non-LTR
      retrotransposons of Drosophila melanogaster are themselves natural triggers of
      homology-dependent gene silencing. We show that, in the female germline of D.
      melanogaster, fragments from the R1 or from the I retrotransposons can mediate
      silencing of chimeric transcription units into which they are inserted. This
      silencing is probably mediated by sequence identity with endogenous copies of the
      retrotransposons because it does not occur with a fragment from the divergent R1
      elements of Bombyx mori, and, when a fragment of I is used, it occurs only in
      females containing functional copies of the I element. This silencing is not
      accompanied by cosuppression of the endogenous gene homologous to the chimeric
      transcription unit, which contrasts to some other silencing mechanisms in
      Drosophila. These observations suggest that in the female germline of D.
      melanogaster the R1 and I retrotransposons may self-regulate their own activity
      and their copy number by triggering homology-dependent gene silencing.

PMID- 12807774
TI  - DNA polymorphism in the beta-Esterase gene cluster of Drosophila melanogaster.
AB  - We have analyzed nucleotide polymorphism within a 5.3-kb region encompassing the
      functional Est-6 gene and the psiEst-6 putative pseudogene in 28 strains of
      Drosophila melanogaster and one of D. simulans. Two divergent sequence types were
      detected, which are not perfectly associated with Est-6 allozyme variation. The
      level of variation (pi) is very close in the 5'-flanking region (0.0059) and Est
      6 gene (0.0057), but significantly higher in the intergenic region (0.0141) and
      putative pseudogene (0.0122). The variation in the 3'-flanking region is
      intermediate (0.0083). These observations may reflect different levels of
      purifying selection in the different regions. Strong linkage disequilibrium
      occurs within the region studied, with the largest values revealed in the
      putative pseudogene and 3'-flanking region. Moreover, recombination is restricted
      within psiEst-6. Gene conversion is detected both within and (to a lesser extent)
      between Est-6 and psiEst-6. The data indicate that psiEst-6 exhibits some
      characteristics that are typical of nonfunctional genes, while other
      characteristics are typically attributed to functional genes; the same situation
      has been observed in other pseudogenes (including Drosophila). The results of
      structural entropy analysis demonstrate higher structural ordering in Est-6 than
      in psiEst-6, in accordance with expectations if psiEst-6 is indeed a pseudogene.
      Taking into account that the function of psiEst-6 is not known (but could exist)
      and following the terminology of J. Brosius and S. J. Gould, we suggest that the
      term "potogene" may be appropriate for psiEst-6, indicating that it is a
      potential gene that may have acquired some distinctive but unknown function.

PMID- 12807775
TI  - Cytoplasmic incompatibility and sperm cyst infection in different Drosophila
      Wolbachia associations.
AB  - Wolbachia are a group of maternally transmitted obligatory intracellular alpha
      proteobacteria that infect a wide range of arthropod and nematode species.
      Wolbachia infection in Drosophila in most cases is associated with the induction
      of cytoplasmic incompatibility (CI), manifested as embryonic lethality of
      offspring in a cross between infected males and uninfected females. While the
      molecular basis of CI is still unknown, it has been suggested that two bacterial
      functions are involved: mod (for modification) modifies the sperm during
      spermatogenesis and resc (for rescue) acts in the female germline and/or in early
      embryos, neutralizing the modification. There is considerable variation in the
      level of incompatibility in different Wolbachia/host interactions. We examine the
      relationship between the levels of CI in a number of naturally infected and
      transinfected Drosophila hosts and the percentage of Wolbachia-infected sperm
      cysts. Our results indicate the presence of two main groups of Drosophila
      Wolbachia associations: group I, which exhibits a positive correlation between CI
      levels and the percentage of infected sperm cysts (mod(+) phenotype), and group
      II, which does not express CI (mod(-) phenotype) irrespective of the infection
      status of the sperm cysts. Group II can be further divided into two subgroups:
      The first one contains associations with high numbers of heavily Wolbachia
      infected sperm cysts while in the second one, Wolbachia is rarely detected in
      sperm cysts, being mostly present in somatic cells. We conclude that there are
      three requirements for the expression of CI in a host-Wolbachia association: (a)
      Wolbachia has to be able to modify sperm (mod(+) genotype), (b) Wolbachia has to
      infect sperm cysts, and (c) Wolbachia has to be harbored by a permissive host.

PMID- 12807776
TI  - Distinct phospholipase C-gamma-dependent signaling pathways in the Drosophila eye
      and wing are revealed by a new small wing allele.
AB  - The Drosophila genome contains a single phospholipase C-gamma (PLC-gamma)
      homolog, encoded by small wing (sl), that acts as an inhibitor of receptor
      tyrosine kinase (RTK) signaling during photoreceptor R7 development. Although the
      existing sl alleles behave genetically as nulls, they may still produce truncated
      Sl products that could in theory still provide limited PLC-gamma function. Both
      to identify a true null allele and to probe structure-function relationships in
      Sl, we carried out an F(1) screen for new sl mutations and identified seven new
      alleles. Flies homozygous for any of these alleles are viable, with the same
      short-wing phenotype described previously; however, two of the alleles differ
      from any of those previously isolated in the severity of the eye phenotype: sl(9)
      homozygotes have a slightly more extreme extra-R7 phenotype, whereas sl(7)
      homozygotes have an almost wild-type eye. We determined the mutant defect in all
      seven alleles, revealing that sl(9) is a molecular null due to a very early stop
      codon, while sl(7) has a missense mutation in the highly conserved Y catalytic
      domain. Together with in vitro mutagenesis of the residue affected by the sl(7)
      mutation, these results confirm the role of Sl in RTK signaling and provide
      evidence for two genetically separable PLC-gamma-dependent pathways affecting the
      development of the eye and the wing.

PMID- 12807777
TI  - The Drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male
      specific lethal dosage compensation complex.
AB  - The Drosophila MSL complex consists of at least six proteins and two noncoding
      roX RNAs that mediate dosage compensation. It acts to remodel the male's X
      chromatin by covalently modifying the amino terminal tails of histones. The roX1
      and roX2 genes are thought to be nucleation sites for assembly and spreading of
      MSL complexes into surrounding chromatin where they roughly double the rates of
      transcription. We generated many transgenic stocks in which the roX1 gene was
      moved from its normal location on the X to new autosomal sites. Approximately 10%
      of such lines displayed unusual sexually dimorphic expression patterns of the
      transgene's mini-white eye-color marker. Males often displayed striking mosaic
      pigmentation patterns similar to those seen in position-effect variegation and
      yet most inserts were in euchromatic locations. In many of these stocks, female
      mini-white expression was very low or absent. The male-specific activation of
      mini-white depended upon the MSL complex. We propose that these transgenes are
      inserted in several different types of repressive chromatin environments that
      inhibit mini-white expression. Males are able to overcome this silencing through
      the action of the MSL complex spreading from the roX1 gene and remodeling the
      local chromatin to allow transcription. The potency with which an ectopic MSL
      complex overcomes silent chromatin suggests that its normal action on the X must
      be under strict regulation.

PMID- 12807778
TI  - The neural receptor protein tyrosine phosphatase DPTP69D is required during
      periods of axon outgrowth in Drosophila.
AB  - We have isolated and characterized a series of 18 chemically induced alleles of
      Ptp69D ranging in strength from viable to worse than null, which represent unique
      tools for probing the structure, function, and signaling pathway of DPTP69D.
      Three alleles are strongly temperature sensitive and were used to define the
      developmental periods requiring DPTP69D function; adult health requires DPTP69D
      during the mid- to late-pupal stage, eclosion requires DPTP69D during the early
      to mid-larval stage, and larval survival requires DPTP69D during embryogenesis.
      Mutations predicted to abolish the phosphatase activity of the membrane proximal
      D1 domain severely reduce but do not abolish DPTP69D function. Six alleles appear
      null; only 20% of null homozygotes pupate and <5% eclose, only to fall into the
      food and drown. One allele, Ptp69D(7), confers axon and viability defects more
      severe than those of the null phenotype. Sequence analysis predicts that
      Ptp69D(7) encodes a mutant protein that may bind but not release substrate. Like
      mutations in the protein tyrosine phosphatase gene Dlar, strong Ptp69D alleles
      cause the ISNb nerve to bypass its muscle targets. Genetic analysis reveals that
      the bypass defect in Dlar and Ptp69D mutants is dependent upon DPTP99A function,
      consistent with the hypothesis that DPTP69D and DLAR both counteract DPTP99A,
      allowing ISNb axons to enter their target muscle field.

PMID- 12807779
TI  - Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila
      ATM/ATR.
AB  - ATM/ATR kinases act as signal transducers in eukaryotic DNA damage and
      replication checkpoints. Mutations in ATM/ATR homologs have pleiotropic effects
      that range from sterility to increased killing by genotoxins in humans, mice, and
      Drosophila. Here we report the generation of a null allele of mei-41, Drosophila
      ATM/ATR homolog, and the use of it to document a semidominant effect on a larval
      mitotic checkpoint and methyl methanesulfonate (MMS) sensitivity. We also tested
      the role of mei-41 in a recently characterized checkpoint that delays
      metaphase/anaphase transition after DNA damage in cellular embryos. We then
      compare five existing mei-41 alleles to the null with respect to known phenotypes
      (female sterility, cell cycle checkpoints, and MMS resistance). We find that not
      all phenotypes are affected equally by each allele, i.e., the functions of MEI-41
      in ensuring fertility, cell cycle regulation, and resistance to genotoxins are
      genetically separable. We propose that MEI-41 acts not in a single rigid signal
      transduction pathway, but in multiple molecular contexts to carry out its many
      functions. Sequence analysis identified mutations, which, for most alleles, fall
      in the poorly characterized region outside the kinase domain; this allowed us to
      tentatively identify additional functional domains of MEI-41 that could be
      subjected to future structure-function studies of this key molecule.

PMID- 12807781
TI  - Change of the heterogametic sex from male to female in the frog.
AB  - Two different types of sex chromosomes, XX/XY and ZZ/ZW, exist in the Japanese
      frog Rana rugosa. They are separated in two local forms that share a common
      origin in hybridization between the other two forms (West Japan and Kanto) with
      male heterogametic sex determination and homomorphic sex chromosomes. In this
      study, to find out how the different types of sex chromosomes differentiated,
      particularly the evolutionary reason for the heterogametic sex change from male
      to female, we performed artificial crossings between the West Japan and Kanto
      forms and mitochondrial 12S rRNA gene sequence analysis. The crossing results
      showed male bias using mother frogs with West Japan cytoplasm and female bias
      using those with Kanto cytoplasm. The mitochondrial genes of ZZ/ZW and XX/XY
      forms, respectively, were similar in sequence to those of the West Japan and
      Kanto forms. These results suggest that in the primary ZZ/ZW form, the West Japan
      strain was maternal and thus male bias was caused by the introgression of the
      Kanto strain while in the primary XX/XY form and vice versa. We therefore
      hypothesize that sex ratio bias according to the maternal origin of the hybrid
      population was a trigger for the sex chromosome differentiation and the change of
      heterogametic sex.

PMID- 12807780
TI  - Molecular evolution and recombination in gender-associated mitochondrial DNAs of
      the Manila clam Tapes philippinarum.
AB  - Doubly uniparental inheritance (DUI) provides an intriguing system for addressing
      aspects of molecular evolution and intermolecular recombination of mitochondrial
      DNA. For this reason, a large sequence analysis has been performed on Tapes
      philippinarum (Bivalvia, Veneridae), which has mitochondrial DNA heteroplasmy
      that is consistent with a DUI. The sequences of a 9.2-kb region (containing 29
      genes) from 9 individuals and the sequences of a single gene from another 44
      individuals are analyzed. Comparisons suggest that the two sex-related
      mitochondrial genomes do not experience a neutral pattern of divergence and that
      selection may act with varying strength on different genes. This pattern of
      evolution may be related to the long, separate history of M and F genomes within
      their tissue-specific "arenas." Moreover, our data suggest that recombinants,
      although occurring in soma, may seldom be transmitted to progeny in T.
      philippinarum.

PMID- 12807782
TI  - Identification of quantitative trait loci for production traits in commercial pig
      populations.
AB  - The aim of this study was to investigate methods for detecting QTL in outbred
      commercial pig populations. Several QTL for back fat and growth rate, previously
      detected in experimental resource populations, were examined for segregation in
      10 different populations. Two hundred trait-by-population-by-chromosome tests
      were performed, resulting in 20 tests being significant at the 5% level. In
      addition, 53 QTL tests for 11 meat quality traits were declared significant,
      using a subset of the populations. These results show that a considerable amount
      of phenotypic variance observed in these populations can be explained by major
      alleles segregating at several of the loci described. Thus, despite a relatively
      strong selection pressure for growth and back fat traits in these populations,
      these alleles have not yet reached fixation. The approaches used here demonstrate
      that it is possible to verify segregation of QTL in commercial populations by
      limited genotyping of a selection of informative animals. Such verified QTL may
      be directly exploited in marker-assisted selection (MAS) programs in commercial
      populations and their molecular basis may be revealed by positional candidate
      cloning.

PMID- 12807783
TI  - Quantitative trait loci variation for growth and obesity between and within lines
      of pigs (Sus scrofa).
AB  - The hypothesis that quantitative trait loci (QTL) that explain variation between
      divergent populations also account for genetic variation within populations was
      tested using pig populations. Two regions of the porcine genome that had
      previously been reported to harbor QTL with allelic effects that differed between
      the modern pig and its wild-type ancestor and between the modern pig and a more
      distantly related population of Asian pigs were studied. QTL for growth and
      obesity traits were mapped using selectively genotyped half-sib families from
      five domesticated modern populations. Strong support was found for at least one
      QTL segregating in each population. For all five populations there was evidence
      of a segregating QTL affecting fatness in a region on chromosome 7. These
      findings confirm that QTL can be detected in highly selected commercial
      populations and are consistent with the hypothesis that the same chromosome
      locations that account for variation between populations also explain genetic
      variation within populations.

PMID- 12807784
TI  - Candidate gene analysis for quantitative traits using the transmission
      disequilibrium test: the example of the melanocortin 4-receptor in pigs.
AB  - Population-wide associations between loci due to linkage disequilibrium can be
      used to map quantitative trait loci (QTL) with high resolution. However, spurious
      associations between markers and QTL can also arise as a consequence of
      population stratification. Statistical methods that cannot differentiate between
      loci associations due to linkage disequilibria from those caused in other ways
      can render false-positive results. The transmission-disequilibrium test (TDT) is
      a robust test for detecting QTL. The TDT exploits within-family associations that
      are not affected by population stratification. However, some TDTs are formulated
      in a rigid form, with reduced potential applications. In this study we generalize
      TDT using mixed linear models to allow greater statistical flexibility. Allelic
      effects are estimated with two independent parameters: one exploiting the robust
      within-family information and the other the potentially biased between-family
      information. A significant difference between these two parameters can be used as
      evidence for spurious association. This methodology was then used to test the
      effects of the fourth melanocortin receptor (MC4R) on production traits in the
      pig. The new analyses supported the previously reported results; i.e., the
      studied polymorphism is either causal or in very strong linkage disequilibrium
      with the causal mutation, and provided no evidence for spurious association.

PMID- 12807785
TI  - PrBn, a major gene controlling homeologous pairing in oilseed rape (Brassica
      napus) haploids.
AB  - Precise control of chromosome pairing is vital for conferring meiotic, and hence
      reproductive, stability in sexually reproducing polyploids. Apart from the Ph1
      locus of wheat that suppresses homeologous pairing, little is known about the
      activity of genes that contribute to the cytological diploidization of
      allopolyploids. In oilseed rape (Brassica napus) haploids, the amount of
      chromosome pairing at metaphase I (MI) of meiosis varies depending on the
      varieties the haploids originate from. In this study, we combined a segregation
      analysis with a maximum-likelihood approach to demonstrate that this variation is
      genetically based and controlled mainly by a gene with a major effect. A total of
      244 haploids were produced from F(1) hybrids between a high- and a low-pairing
      variety (at the haploid stage) and their meiotic behavior at MI was
      characterized. Likelihood-ratio statistics were used to demonstrate that the
      distribution of the number of univalents among these haploids was consistent with
      the segregation of a diallelic major gene, presumably in a background of
      polygenic variation. Our observations suggest that this gene, named PrBn, is
      different from Ph1 and could thus provide complementary information on the
      meiotic stabilization of chromosome pairing in allopolyploid species.

PMID- 12807787
TI  - A centromeric tandem repeat family originating from a part of Ty3/gypsy
      retroelement in wheat and its relatives.
AB  - From a wild diploid species that is a relative of wheat, Aegilops speltoides, a
      301-bp repeat containing 16 copies of a CAA microsatellite was isolated. Southern
      blot and fluorescence in situ hybridization revealed that approximately 250 bp of
      the sequence is tandemly arrayed at the centromere regions of A- and B-genome
      chromosomes of common wheat and rye chromosomes. Although the DNA sequence of
      this 250-bp repeat showed no notable homology in the databases, the flanking or
      intervening sequences between the repeats showed high homologies (>82%) to two
      separate sequences of the gag gene and its upstream region in cereba, a Ty3/gypsy
      like retroelement of Hordeum vulgare. Since the amino acid sequence deduced from
      the 250 bp with seven CAAs showed some similarity ( approximately 53%) to that of
      the gag gene, we concluded that the 250-bp repeats had also originated from the
      cereba-like retroelements in diploid wheat such as Ae. speltoides and had formed
      tandem arrays, whereas the 300-bp repeats were dispersed as a part of cereba-like
      retroelements. This suggests that some tandem repeats localized at the
      centromeric regions of cereals and other plant species originated from parts of
      retrotransposons.

PMID- 12807786
TI  - Map-based cloning of leaf rust resistance gene Lr21 from the large and polyploid
      genome of bread wheat.
AB  - We report the map-based cloning of the leaf rust resistance gene Lr21, previously
      mapped to a gene-rich region at the distal end of chromosome arm 1DS of bread
      wheat (Triticum aestivum L.). Molecular cloning of Lr21 was facilitated by
      diploid/polyploid shuttle mapping strategy. Cloning of Lr21 was confirmed by
      genetic transformation and by a stably inherited resistance phenotype in
      transgenic plants. Lr21 spans 4318 bp and encodes a 1080-amino-acid protein
      containing a conserved nucleotide-binding site (NBS) domain, 13 imperfect leucine
      rich repeats (LRRs), and a unique 151-amino-acid sequence missing from known NBS
      LRR proteins at the N terminus. Fine-structure genetic analysis at the Lr21 locus
      detected a noncrossover (recombination without exchange of flanking markers)
      within a 1415-bp region resulting from either a gene conversion tract of at least
      191 bp or a double crossover. The successful map-based cloning approach as
      demonstrated here now opens the door for cloning of many crop-specific agronomic
      traits located in the gene-rich regions of bread wheat.

PMID- 12807788
TI  - A large rearrangement involving genes and low-copy DNA interrupts the
      microcollinearity between rice and barley at the Rph7 locus.
AB  - Grass genomes differ greatly in chromosome number, ploidy level, and size.
      Despite these differences, very good conservation of the marker order
      (collinearity) was found at the genetic map level between the different grass
      genomes. Collinearity is particularly good between rice chromosome 1 and the
      group 3 chromosomes in the Triticeae. We have used this collinearity to saturate
      the leaf rust resistance locus Rph7 on chromosome 3HS in barley with ESTs
      originating from rice chromosome 1S. Chromosome walking allowed the establishment
      of a contig of 212 kb spanning the Rph7 resistance gene. Sequencing of the contig
      showed an average gene density of one gene/20 kb with islands of higher density.
      Comparison with the orthologous rice sequence revealed the complete conservation
      of five members of the HGA gene family whereas intergenic regions differ greatly
      in size and composition. In rice, the five genes are closely associated whereas
      in barley intergenic regions are >38-fold larger. The size difference is due
      mainly to the presence of six additional genes as well as noncoding low-copy
      sequences. Our data suggest that a major rearrangement occurred in this region
      since the Triticeae and rice lineage diverged.

PMID- 12807789
TI  - Characterization of high-copy-number retrotransposons from the large genomes of
      the louisiana iris species and their use as molecular markers.
AB  - The Louisiana iris species Iris brevicaulis and I. fulva are morphologically and
      karyotypically distinct yet frequently hybridize in nature. A group of high-copy
      number TY3/gypsy-like retrotransposons was characterized from these species and
      used to develop molecular markers that take advantage of the abundance and
      distribution of these elements in the large iris genome. The copy number of these
      IRRE elements (for iris retroelement), is approximately 1 x 10(5), accounting for
      approximately 6-10% of the approximately 10,000-Mb haploid Louisiana iris genome.
      IRRE elements are transcriptionally active in I. brevicaulis and I. fulva and
      their F(1) and backcross hybrids. The LTRs of the elements are more variable than
      the coding domains and can be used to define several distinct IRRE subfamilies.
      Transposon display or S-SAP markers specific to two of these subfamilies have
      been developed and are highly polymorphic among wild-collected individuals of
      each species. As IRRE elements are present in each of 11 iris species tested, the
      marker system has the potential to provide valuable comparative data on the
      dynamics of retrotransposition in large plant genomes.

PMID- 12807790
TI  - Four loci on abnormal chromosome 10 contribute to meiotic drive in maize.
AB  - We provide a genetic analysis of the meiotic drive system on maize abnormal
      chromosome 10 (Ab10) that causes preferential segregation of specific chromosomal
      regions to the reproductive megaspore. The data indicate that at least four
      chromosomal regions contribute to meiotic drive, each providing distinct
      functions that can be differentiated from each other genetically and/or
      phenotypically. Previous reports established that meiotic drive requires
      neocentromere activity at specific tandem repeat arrays (knobs) and that two
      regions on Ab10 are involved in trans-activating neocentromeres. Here we confirm
      and extend data suggesting that only one of the neocentromere-activating regions
      is sufficient to move many knobs. We also confirm the localization of a
      locus/loci on Ab10, thought to be a prerequisite for meiotic drive, which
      promotes recombination in structural heterozygotes. In addition, we identified
      two new and independent functions required for meiotic drive. One was identified
      through the characterization of a deletion derivative of Ab10 [Df(L)] and another
      as a newly identified meiotic drive mutation (suppressor of meiotic drive 3). In
      the absence of either function, meiotic drive is abolished but neocentromere
      activity and the recombination effect typical of Ab10 are unaffected. These
      results demonstrate that neocentromere activity and increased recombination are
      not the only events required for meiotic drive.

PMID- 12807791
TI  - Analysis of natural allelic variation at seed dormancy loci of Arabidopsis
      thaliana.
AB  - Arabidopsis accessions differ largely in their seed dormancy behavior. To
      understand the genetic basis of this intraspecific variation we analyzed two
      accessions: the laboratory strain Landsberg erecta (Ler) with low dormancy and
      the strong-dormancy accession Cape Verde Islands (Cvi). We used a quantitative
      trait loci (QTL) mapping approach to identify loci affecting the after-ripening
      requirement measured as the number of days of seed dry storage required to reach
      50% germination. Thus, seven QTL were identified and named delay of germination
      (DOG) 1-7. To confirm and characterize these loci, we developed 12 near-isogenic
      lines carrying single and double Cvi introgression fragments in a Ler genetic
      background. The analysis of these lines for germination in water confirmed four
      QTL (DOG1, DOG2, DOG3, and DOG6) as showing large additive effects in Ler
      background. In addition, it was found that DOG1 and DOG3 genetically interact,
      the strong dormancy determined by DOG1-Cvi alleles depending on DOG3-Ler alleles.
      These genotypes were further characterized for seed dormancy/germination behavior
      in five other test conditions, including seed coat removal, gibberellins, and an
      abscisic acid biosynthesis inhibitor. The role of the Ler/Cvi allelic variation
      in affecting dormancy is discussed in the context of current knowledge of
      Arabidopsis germination.

PMID- 12807792
TI  - Spectrum of chemically induced mutations from a large-scale reverse-genetic
      screen in Arabidopsis.
AB  - Chemical mutagenesis has been the workhorse of traditional genetics, but it has
      not been possible to determine underlying rates or distributions of mutations
      from phenotypic screens. However, reverse-genetic screens can be used to provide
      an unbiased ascertainment of mutation statistics. Here we report a comprehensive
      analysis of approximately 1900 ethyl methanesulfonate (EMS)-induced mutations in
      192 Arabidopsis thaliana target genes from a large-scale TILLING reverse-genetic
      project, about two orders of magnitude larger than previous such efforts. From
      this large data set, we are able to draw strong inferences about the occurrence
      and randomness of chemically induced mutations. We provide evidence that we have
      detected the large majority of mutations in the regions screened and confirm the
      robustness of the high-throughput TILLING method; therefore, any deviations from
      randomness can be attributed to selectional or mutational biases. Overall, we
      detect twice as many heterozygotes as homozygotes, as expected; however, for
      mutations that are predicted to truncate an encoded protein, we detect a ratio of
      3.6:1, indicating selection against homozygous deleterious mutations. As expected
      for alkylation of guanine by EMS, >99% of mutations are G/C-to-A/T transitions. A
      nearest-neighbor bias around the mutated base pair suggests that mismatch repair
      counteracts alkylation damage.

PMID- 12807793
TI  - On the determination of recombination rates in intermated recombinant inbred
      populations.
AB  - The recurrent intermating of F(2) individuals for some number of generations
      followed by several generations of inbreeding produces an intermated recombinant
      inbred (IRI) population. Such populations are currently being developed in the
      plant-breeding community because linkage associations present in an F(2)
      population are broken down and a population of fixed inbred lines is also
      created. The increased levels of recombination enable higher-resolution mapping
      in IRI populations relative to F(2) populations. Herein we derive relationships,
      under several limiting assumptions, for determining the expected recombination
      fraction in IRI populations from the crossover rate per meiosis. These
      relationships are applicable to situations where the inbreeding component of IRI
      population development is by either self-fertilization or full-sib mating.
      Additionally, we show that the derived equations can be solved for the crossover
      rate per meiosis if the recombination fraction is known for the IRI population.
      Thus, the observed recombination fraction in any IRI population can be expressed
      on an F(2) basis. The implications of this work on the expansion of genetic maps
      in IRI populations and limits for detecting linkage between markers are also
      considered.

PMID- 12807794
TI  - Maximum-likelihood estimation of admixture proportions from genetic data.
AB  - For an admixed population, an important question is how much genetic contribution
      comes from each parental population. Several methods have been developed to
      estimate such admixture proportions, using data on genetic markers sampled from
      parental and admixed populations. In this study, I propose a likelihood method to
      estimate jointly the admixture proportions, the genetic drift that occurred to
      the admixed population and each parental population during the period between the
      hybridization and sampling events, and the genetic drift in each ancestral
      population within the interval between their split and hybridization. The results
      from extensive simulations using various combinations of relevant parameter
      values show that in general much more accurate and precise estimates of admixture
      proportions are obtained from the likelihood method than from previous methods.
      The likelihood method also yields reasonable estimates of genetic drift that
      occurred to each population, which translate into relative effective sizes (N(e))
      or absolute average N(e)'s if the times when the relevant events (such as
      population split, admixture, and sampling) occurred are known. The proposed
      likelihood method also has features such as relatively low computational
      requirement compared with previous ones, flexibility for admixture models, and
      marker types. In particular, it allows for missing data from a contributing
      parental population. The method is applied to a human data set and a wolflike
      canids data set, and the results obtained are discussed in comparison with those
      from other estimators and from previous studies.

PMID- 12807795
TI  - Fixation probability and time in subdivided populations.
AB  - New alleles arising in a population by mutation ultimately are either fixed or
      lost. Either is possible, for both beneficial and deleterious alleles, because of
      stochastic changes in allele frequency due to genetic drift. Spatially structured
      populations differ from unstructured populations in the probability of fixation
      and the time that this fixation takes. Previous results have generally made many
      assumptions: that all demes contribute to the next generation in exact proportion
      to their current sizes, that new mutations are beneficial, and that new alleles
      have additive effects. In this article these assumptions are relaxed, allowing
      for an arbitrary distribution among demes of reproductive success, both
      beneficial and deleterious effects, and arbitrary dominance. The effects of
      population structure can be expressed with two summary statistics: the effective
      population size and a variant of Wright's F(ST). In general, the probability of
      fixation is strongly affected by population structure, as is the expected time to
      fixation or loss. Population structure changes the effective size of the species,
      often strongly downward; smaller effective size increases the probability of
      fixing deleterious alleles and decreases the probability of fixing beneficial
      alleles. On the other hand, population structure causes an increase in the
      homozygosity of alleles, which increases the probability of fixing beneficial
      alleles but somewhat decreases the probability of fixing deleterious alleles. The
      probability of fixing new beneficial alleles can be simply described by 2hs(1 -
      F(ST))N(e)/N(tot), where hs is the change in fitness of heterozygotes relative to
      the ancestral homozygote, F(ST) is a weighted version of Wright's measure of
      population subdivision, and N(e) and N(tot) are the effective and census sizes,
      respectively. These results are verified by simulation for a broad range of
      population structures, including the island model, the stepping-stone model, and
      a model with extinction and recolonization.

PMID- 12807796
TI  - Likelihood-based estimation of microsatellite mutation rates.
AB  - Microsatellites are widely used in genetic analyses, many of which require
      reliable estimates of microsatellite mutation rates, yet the factors determining
      mutation rates are uncertain. The most straightforward and conclusive method by
      which to study mutation is direct observation of allele transmissions in parent
      child pairs, and studies of this type suggest a positive, possibly exponential,
      relationship between mutation rate and allele size, together with a bias toward
      length increase. Except for microsatellites on the Y chromosome, however,
      previous analyses have not made full use of available data and may have
      introduced bias: mutations have been identified only where child genotypes could
      not be generated by transmission from parents' genotypes, so that the probability
      that a mutation is detected depends on the distribution of allele lengths and
      varies with allele length. We introduce a likelihood-based approach that has two
      key advantages over existing methods. First, we can make formal comparisons
      between competing models of microsatellite evolution; second, we obtain
      asymptotically unbiased and efficient parameter estimates. Application to data
      composed of 118,866 parent-offspring transmissions of AC microsatellites supports
      the hypothesis that mutation rate increases exponentially with microsatellite
      length, with a suggestion that contractions become more likely than expansions as
      length increases. This would lead to a stationary distribution for allele length
      maintained by mutational balance. There is no evidence that contractions and
      expansions differ in their step size distributions.

PMID- 12807797
TI  - Selection in a subdivided population with local extinction and recolonization.
AB  - In a subdivided population, local extinction and subsequent recolonization affect
      the fate of alleles. Of particular interest is the interaction of this force with
      natural selection. The effect of selection can be weakened by this additional
      source of stochastic change in allele frequency. The behavior of a selected
      allele in such a population is shown to be equivalent to that of an allele with a
      different selection coefficient in an unstructured population with a different
      size. This equivalence allows use of established results for panmictic
      populations to predict such quantities as fixation probabilities and mean times
      to fixation. The magnitude of the quantity N(e)s(e), which determines fixation
      probability, is decreased by extinction and recolonization. Thus deleterious
      alleles are more likely to fix, and advantageous alleles less likely to do so, in
      the presence of extinction and recolonization. Computer simulations confirm that
      the theoretical predictions of both fixation probabilities and mean times to
      fixation are good approximations.

PMID- 12807798
TI  - Estimating mutation rate: how to count mutations?
AB  - Mutation rate is an essential parameter in genetic research. Counting the number
      of mutant individuals provides information for a direct estimate of mutation
      rate. However, mutant individuals in the same family can share the same mutations
      due to premeiotic mutation events, so that the number of mutant individuals can
      be significantly larger than the number of mutation events observed. Since
      mutation rate is more closely related to the number of mutation events, whether
      one should count only independent mutation events or the number of mutants
      remains controversial. We show in this article that counting mutant individuals
      is a correct approach for estimating mutation rate, while counting only mutation
      events will result in underestimation. We also derived the variance of the
      mutation-rate estimate, which allows us to examine a number of important issues
      about the design of such experiments. The general strategy of such an experiment
      should be to sample as many families as possible and not to sample much more
      offspring per family than the reciprocal of the pairwise correlation coefficient
      within each family. To obtain a reasonably accurate estimate of mutation rate,
      the number of sampled families needs to be in the same or higher order of
      magnitude as the reciprocal of the mutation rate.

PMID- 12807799
TI  - Comparing analysis methods for mutation-accumulation data: a simulation study.
AB  - We simulated single-generation data for a fitness trait in mutation-accumulation
      (MA) experiments, and we compared three methods of analysis. Bateman-Mukai (BM)
      and maximum likelihood (ML) need information on both the MA lines and control
      lines, while minimum distance (MD) can be applied with or without the control.
      Both MD and ML assume gamma-distributed mutational effects. ML estimates of the
      rate of deleterious mutation had larger mean square error (MSE) than MD or BM had
      due to large outliers. MD estimates obtained by ignoring the mean decline
      observed from comparison to a control are often better than those obtained using
      that information. When effects are simulated using the gamma distribution,
      reducing the precision with which the trait is assayed increases the probability
      of obtaining no ML or MD estimates but causes no appreciable increase of the MSE.
      When the residual errors for the means of the simulated lines are sampled from
      the empirical distribution in a MA experiment, instead of from a normal one, the
      MSEs of BM, ML, and MD are practically unaffected. When the simulated gamma
      distribution accounts for a high rate of mild deleterious mutation, BM detects
      only approximately 30% of the true deleterious mutation rate, while MD or ML
      detects substantially larger fractions. To test the robustness of the methods, we
      also added a high rate of common contaminant mutations with constant mild
      deleterious effect to a low rate of mutations with gamma-distributed deleterious
      effects and moderate average. In that case, BM detects roughly the same fraction
      as before, regardless of the precision of the assay, while ML fails to provide
      estimates. However, MD estimates are obtained by ignoring the control
      information, detecting approximately 70% of the total mutation rate when the mean
      of the lines is assayed with good precision, but only 15% for low-precision
      assays. Contaminant mutations with only tiny deleterious effects could not be
      detected with acceptable accuracy by any of the above methods.

PMID- 12807800
TI  - An argonaute-like protein is required for meiotic silencing.
AB  - We demonstrate the involvement of suppressor of meiotic silencing-2 (sms-2(+)), a
      Neurospora gene coding for an Argonaute-like protein, in meiotic silencing and
      normal sexual development.

PMID- 12807801
TI  - False discovery rate in linkage and association genome screens for complex
      disorders.
AB  - We explore the implications of the false discovery rate (FDR) controlling
      procedure in disease gene mapping. With the aid of simulations, we show how,
      under models commonly used, the simple step-down procedure introduced by
      Benjamini and Hochberg controls the FDR for the dependent tests on which linkage
      and association genome screens are based. This adaptive multiple comparison
      procedure may offer an important tool for mapping susceptibility genes for
      complex diseases.

PMID- 12807802
TI  - Design of a national retail data monitor for public health surveillance.
AB  - The National Retail Data Monitor receives data daily from 10,000 stores,
      including pharmacies, that sell health care products. These stores belong to
      national chains that process sales data centrally and utilize Universal Product
      Codes and scanners to collect sales information at the cash register. The high
      degree of retail sales data automation enables the monitor to collect information
      from thousands of store locations in near to real time for use in public health
      surveillance. The monitor provides user interfaces that display summary sales
      data on timelines and maps. Algorithms monitor the data automatically on a daily
      basis to detect unusual patterns of sales. The project provides the resulting
      data and analyses, free of charge, to health departments nationwide. Future plans
      include continued enrollment and support of health departments, developing
      methods to make the service financially self-supporting, and further refinement
      of the data collection system to reduce the time latency of data receipt and
      analysis.

PMID- 12807803
TI  - Technical description of RODS: a real-time public health surveillance system.
AB  - This report describes the design and implementation of the Real-time Outbreak and
      Disease Surveillance (RODS) system, a computer-based public health surveillance
      system for early detection of disease outbreaks. Hospitals send RODS data from
      clinical encounters over virtual private networks and leased lines using the
      Health Level 7 (HL7) message protocol. The data are sent in real time. RODS
      automatically classifies the registration chief complaint from the visit into one
      of seven syndrome categories using Bayesian classifiers. It stores the data in a
      relational database, aggregates the data for analysis using data warehousing
      techniques, applies univariate and multivariate statistical detection algorithms
      to the data, and alerts users of when the algorithms identify anomalous patterns
      in the syndrome counts. RODS also has a Web-based user interface that supports
      temporal and spatial analyses. RODS processes sales of over-the-counter health
      care products in a similar manner but receives such data in batch mode on a daily
      basis. RODS was used during the 2002 Winter Olympics and currently operates in
      two states-Pennsylvania and Utah. It has been and continues to be a resource for
      implementing, evaluating, and applying new methods of public health surveillance.

PMID- 12807804
TI  - Is there a digital divide among physicians? A geographic analysis of information
      technology in Southern California physician offices.
AB  - OBJECTIVE: The aim of this study was to determine whether physician offices
      located in high-minority and low-income neighborhoods have different levels of
      access to information technology than offices located in lower-minority and
      higher-income areas. DESIGN: A cross-sectional survey was conducted of
      pediatrics, family medicine, and general practice offices in Orange County,
      California. Survey data were linked with community demographic data from the 2000
      Census using a geographical information system. RESULTS: Of 307 offices surveyed,
      141 responded (46%). Offices located in high-minority and high-poverty areas were
      as likely to respond as other offices. Among responding offices, 94% had a
      computer, 77% had Web access, 29% had broadband Internet access, and 53% used
      computerized scheduling and billing systems. Offices located in minority and low
      income communities had equivalent access to each technology. Offices in
      communities with larger proportions of Hispanics were less likely to have
      practice Web pages, but other uses of the Internet were not associated with
      practice location. Offices reported high levels of interest in online clinical
      systems but also high levels of concern about these systems' usability and
      confidentiality. Offices with Web access and those with practice management
      systems expressed greater interest in online clinical systems but also greater
      levels of concern about usability and confidentiality. These attitudes were
      equivalent among offices in different communities. CONCLUSION: Primary care
      offices located in poor and minority communities in a large, suburban county had
      high levels of access to and interest in Web-based systems. Physicians' offices
      may therefore provide a venue for online services aimed at improving health
      outcomes for poor and minority communities. Research is needed in other
      geographic regions to determine the generalizability of these findings.

PMID- 12807805
TI  - Creating a text classifier to detect radiology reports describing mediastinal
      findings associated with inhalational anthrax and other disorders.
AB  - OBJECTIVE: The aim of this study was to create a classifier for automatic
      detection of chest radiograph reports consistent with the mediastinal findings of
      inhalational anthrax. DESIGN: The authors used the Identify Patient Sets (IPS)
      system to create a key word classifier for detecting reports describing
      mediastinal findings consistent with anthrax and compared their performances on a
      test set of 79,032 chest radiograph reports. MEASUREMENTS: Area under the ROC
      curve was the main outcome measure of the IPS classifier. Sensitivity and
      specificity of an initial IPS model were calculated based on an existing key word
      search and were compared against a Boolean version of the IPS classifier.
      RESULTS: The IPS classifier received an area under the ROC curve of 0.677 (90% CI
      = 0.628 to 0.772) with a specificity of 0.99 and maximum sensitivity of 0.35. The
      initial IPS model attained a specificity of 1.0 and a sensitivity of 0.04.
      CONCLUSION: The IPS system is a useful tool for helping domain experts create a
      statistical key word classifier for textual reports that is a potentially useful
      component in surveillance of radiographic findings suspicious for anthrax.

PMID- 12807806
TI  - Achieving evolvable Web-database bioscience applications using the EAV/CR
      framework: recent advances.
AB  - The EAV/CR framework, designed for database support of rapidly evolving
      scientific domains, utilizes metadata to facilitate schema maintenance and
      automatic generation of Web-enabled browsing interfaces to the data. EAV/CR is
      used in SenseLab, a neuroscience database that is part of the national Human
      Brain Project. This report describes various enhancements to the framework. These
      include (1) the ability to create "portals" that present different subsets of the
      schema to users with a particular research focus, (2) a generic XML-based
      protocol to assist data extraction and population of the database by external
      agents, (3) a limited form of ad hoc data query, and (4) semantic descriptors for
      interclass relationships and links to controlled vocabularies such as the UMLS.

PMID- 12807807
TI  - Development of a clinical data warehouse for hospital infection control.
AB  - Existing data stored in a hospital's transactional servers have enormous
      potential to improve performance measurement and health care quality. Accessing,
      organizing, and using these data to support research and quality improvement
      projects are evolving challenges for hospital systems. The authors report
      development of a clinical data warehouse that they created by importing data from
      the information systems of three affiliated public hospitals. They describe their
      methodology; difficulties encountered; responses from administrators, computer
      specialists, and clinicians; and the steps taken to capture and store patient
      level data. The authors provide examples of their use of the clinical data
      warehouse to monitor antimicrobial resistance, to measure antimicrobial use, to
      detect hospital-acquired bloodstream infections, to measure the cost of
      infections, and to detect antimicrobial prescribing errors. In addition, they
      estimate the amount of time and money saved and the increased precision achieved
      through the practical application of the data warehouse.

PMID- 12807808
TI  - Comparing paper-based with electronic patient records: lessons learned during a
      study on diagnosis and procedure codes.
AB  - Paper-based and electronic patient records generally are used in parallel to
      support different tasks. Many studies comparing their quality do not report
      sufficiently on the methods used. Few studies refer to the patient. Instead, most
      regard the paper record as the gold standard. Focusing on quality criteria, the
      current study compared the two records patient by patient, presuming that each
      might hold unique advantages. For surgical patients at a nonuniversity hospital,
      diagnosis and procedure codes from the hospital's electronic patient record (EPR
      set) were compared with the paper records (PPR set). Diagnosis coding from the
      paper-based patient record resulted in minor qualitative advantages. The EPR
      documentation showed potential advantages in both quality and quantity of
      procedure coding. As in many previous studies, the current study relied on a
      single individual to extract and transform contents from the paper record to
      compare PPR with EPR. The exploratory study, although limited, supports previous
      views of the complementary nature of paper and electronic records. The lessons
      learned from this study are that medical professionals should be cognizant of the
      possible discrepancies between paper and electronic information and look toward
      combining information from both records whenever appropriate. The inadequate
      methodology (transformations done by a single individual) used in the authors'
      study is typical of other studies in the field. The limited generalizability and
      restricted reproducibility of this commonly used approach emphasize the need to
      improve methods for comparing paper-based with electronic versions of a patient's
      chart.

PMID- 12807809
TI  - Falls prevention within the Australian general practice data model: methodology,
      information model, and terminology issues.
AB  - The iterative development of the Falls Risk Assessment and Management System
      (FRAMS) drew upon research evidence and early consumer and clinician input
      through focus groups, interviews, direct observations, and an online
      questionnaire. Clinical vignettes were used to validate the clinical model and
      program logic, input, and output. The information model was developed within the
      Australian General Practice Data Model (GPDM) framework. The online FRAMS
      implementation used available Internet (TCP/IP), messaging (HL7, XML), knowledge
      representation (Arden Syntax), and classification (ICD10-AM, ICPC2) standards.
      Although it could accommodate most of the falls prevention information elements,
      the GPDM required extension for prevention and prescribing risk management.
      Existing classifications could not classify all falls prevention concepts. The
      lack of explicit rules for terminology and data definitions allowed multiple
      concept representations across the terminology-architecture interface. Patients
      were more enthusiastic than clinicians. A usable standards-based online
      distributed decision support system for falls prevention can be implemented
      within the GPDM, but a comprehensive terminology is required. The conceptual
      interface between terminology and architecture requires standardization,
      preferably within a reference information model. Developments in electronic
      decision support must be guided by evidence-based clinical and information models
      and knowledge ontologies. The safety and quality of knowledge-based decision
      support systems must be monitored. Further examination of falls and other
      clinical domains within the GPDM is needed.

PMID- 12807810
TI  - Computer decision support as a source of interpretation error: the case of
      electrocardiograms.
AB  - OBJECTIVE: The aim of this study was to determine the effect that the computer
      interpretation (CI) of electrocardiograms (EKGs) has on the accuracy of resident
      (noncardiologist) physicians reading EKGs. DESIGN: A randomized, controlled trial
      was conducted in a laboratory setting from February through June 2001, using a
      two-period crossover design with matched pairs of subjects randomly assigned to
      sequencing groups. MEASUREMENTS: Subjects' interpretive accuracy of discrete,
      cardiologist-determined EKG findings were measured as judged by a board-certified
      internist. RESULTS: Without the CI, subjects interpreted 48.9% (95% confidence
      interval, 45.0% to 52.8%) of the findings correctly. With the CI, subjects
      interpreted 55.4% (51.9% to 58.9%) correctly (p < 0.0001). When the CIs that
      agreed with the gold standard (Correct CIs) were not included, 53.1% (47.7% to
      58.5%) of the findings were interpreted correctly. When the correct CI was
      included, accuracy increased to 68.1% (63.2% to 72.7%; p < 0.0001). When computer
      advice that did not agree with the gold standard (Incorrect CI) was not provided
      to the subjects, 56.7% (48.5% to 64.5%) of findings were interpreted correctly.
      Accuracy dropped to 48.3% (40.4% to 56.4%) when the incorrect computer advice was
      provided (p = 0.131). Subjects erroneously agreed with the incorrect CI more
      often when it was presented with the EKG 67.7% (57.2% to 76.7%) than when it was
      not 34.6% (23.8% to 47.3%; p < 0.0001). CONCLUSIONS: Computer decision support
      systems can generally improve the interpretive accuracy of internal medicine
      residents in reading EKGs. However, subjects were influenced significantly by
      incorrect advice, which tempers the overall usefulness of computer-generated
      advice in this and perhaps other areas.

PMID- 12807811
TI  - AsthmaCritic: issues in designing a noninquisitive critiquing system for daily
      practice.
AB  - The noninquisitive critiquing system, AsthmaCritic, uses routinely recorded
      electronic patient data to select and analyze records of patients with asthma or
      chronic obstructive pulmonary disease (COPD). The system generates critiquing
      comments and adds these comments to the patient record. The system was developed
      by using and expanding an existing generic critiquing system. After a brief
      overview of the system, this report focuses on the authors' design choices in
      light of existing literature and the issues that underlie these design choices.
      Currently, AsthmaCritic is used by primary care physicians and is undergoing
      clinical evaluation.

PMID- 12807812
TI  - The syntax and semantics of the PROforma guideline modeling language.
AB  - PROforma is an executable process modeling language that has been used
      successfully to build and deploy a range of decision support systems, guidelines,
      and other clinical applications. It is one of a number of recent proposals for
      representing clinical protocols and guidelines in a machine-executable format
      (see <www.openclinical.org>). In this report, the authors outline the task model
      for the language and provide an operational semantics for process enactment
      together with a semantics for expressions, which may be used to query the state
      of a task during enactment. The operational semantics includes a number of public
      operations that may be performed on an application by an external agent,
      including operations that change the values of data items, recommend or make
      decisions, manage tasks that have been performed, and perform any task state
      changes that are implied by the current state of the application. Disclosure:
      PROforma has been used as the basis of a commercial decision support and
      guideline technology Arezzo (Infermed, London, UK; details in text).

PMID- 12807813
TI  - Transparent ICD and DRG coding using information technology: linking and
      associating information sources with the eXtensible Markup Language.
AB  - With the introduction of ICD-10 as the standard for diagnostics, it becomes
      necessary to develop an electronic representation of its complete content,
      inherent semantics, and coding rules. The authors' design relates to the current
      efforts by the CEN/TC 251 to establish a European standard for hierarchical
      classification systems in health care. The authors have developed an electronic
      representation of ICD-10 with the eXtensible Markup Language (XML) that
      facilitates integration into current information systems and coding software,
      taking different languages and versions into account. In this context, XML
      provides a complete processing framework of related technologies and standard
      tools that helps develop interoperable applications. XML provides semantic
      markup. It allows domain-specific definition of tags and hierarchical document
      structure. The idea of linking and thus combining information from different
      sources is a valuable feature of XML. In addition, XML topic maps are used to
      describe relationships between different sources, or "semantically associated"
      parts of these sources. The issue of achieving a standardized medical vocabulary
      becomes more and more important with the stepwise implementation of
      diagnostically related groups, for example. The aim of the authors' work is to
      provide a transparent and open infrastructure that can be used to support
      clinical coding and to develop further software applications. The authors are
      assuming that a comprehensive representation of the content, structure, inherent
      semantics, and layout of medical classification systems can be achieved through a
      document-oriented approach.

PMID- 12807814
TI  - Developing and evaluating criteria to help reviewers of biomedical informatics
      manuscripts.
AB  - Peer-reviewed publication of scientific research results represents the most
      important means of their communication. The authors have annually reviewed a
      large heterogeneous set of papers to produce the International Medical
      Informatics Association (IMIA) Yearbook of Medical Informatics. To support an
      objective and high-quality review process, the authors attempted to provide
      reviewers with a set of refined quality criteria, comprised of 80 general
      criteria and an additional 60 criteria for specific types of manuscripts. Authors
      conducted a randomized controlled trial, with 18 reviewers, to evaluate
      application of the refined criteria on review outcomes. Whereas the trial found
      that reviewers applying the criteria graded papers more strictly (lower overall
      scores), and that junior reviewers appreciated the availability of the criteria,
      there was no overall change in the interrater variability in reviewing the
      manuscripts. The authors describe their experience as a "case report" and provide
      a reference to the refined quality review criteria without claiming that the
      criteria represent a validated instrument for quantitative quality measurement.

PMID- 12807815
TI  - Multimedia software to help caregivers cope.
AB  - OBJECTIVE: This report describes the design and evaluation of a software
      application to help carers cope when faced with caring problems and emergencies.
      DESIGN: The design process involved users at each stage to ensure the content of
      the software application was appropriate, and the research team carefully
      considered the requirements of disabled and elderly users. MEASUREMENTS: Focus
      group discussions and individual interviews were conducted in five European
      countries to ascertain the needs of caregivers in this area. The findings were
      used to design a three-part multimedia software application to help family
      caregivers prepare to cope with sudden, unexpected, and difficult situations that
      may arise during their time as a caregiver. This prototype then was evaluated via
      user trials and usability questionnaires to consider the usability and acceptance
      of the application and any changes that may be required. RESULTS: User acceptance
      of the software application was high, and the key features of usability such as
      content, appearance, and navigation were highly rated. In general, comments were
      positive and enthusiastic regarding the content of the software application and
      relevance to the caring situation. CONCLUSION: The software application has the
      potential to offer information and support to those who are caring for the
      elderly and disabled at home and to help them prepare for a crisis.

PMID- 12807816
TI  - Predicting proteasomal cleavage sites: a comparison of available methods.
AB  - The proteasome plays an essential role in the immune responses of vertebrates. By
      degrading intercellular proteins from self and non-self, the proteasome produces
      the majority of the peptides that are presented to cytotoxic T cells (CTL). There
      is accumulating evidence that the C-terminal, in particular, of CTL epitopes is
      cleaved precisely by the proteasome, whereas the N-terminal is produced with an
      extension, and later trimmed by peptidases in the cytoplasm and in the
      endoplasmic reticulum. Recently, three publicly available methods have been
      developed for prediction of the specificity of the proteasome. Here, we compare
      the performance of these methods on a large set of CTL epitopes. The best method,
      NetChop at www.cbs.dtu.dk/Services/NetChop, can capture approximately 70% of the
      C-termini correctly. This result suggests that the predictions can still be
      improved, particularly if more quantitative degradation data become available.

PMID- 12807817
TI  - Specific depletion of autoreactive B lymphocytes by a recombinant fusion protein
      in vitro and in vivo.
AB  - Antigen-specific B cells are key players in many autoimmune diseases through the
      production of autoreactive antibodies that can cause severe tissue damage and
      malfunction. We have designed and expressed a fusion protein, referred to as MOG
      Fc, composed of the extracellular Ig-like domain of human myelin oligodendrocyte
      glycoprotein (MOG) and the C(H)2 and C(H)3 domains of the human IgG1 heavy chain.
      The dimerized fusion protein was capable of mediating cytotoxicity against a MOG
      reactive hybridoma line in vitro. Likewise, MOG-Fc significantly reduced the
      number of circulating MOG-reactive B cells in an anti-MOG Ig heavy chain knock-in
      mouse model. Our study shows that autoantigen-reactive B lymphocytes can be
      efficiently and selectively eliminated by an autoantigen Fcgamma1 fusion protein
      in vitro as well as in vivo. Such fusion proteins may provide a platform for the
      development of highly selective therapeutic approaches.

PMID- 12807818
TI  - Successful elimination of large established tumors and avoidance of antigen-loss
      variants by aggressive adoptive T cell immunotherapy.
AB  - Utilization of ex vivo-expanded epitope-specific cytotoxic T lymphocytes has
      become a clinical standard in the adoptive immunotherapy of tumors. One of the
      obstacles faced by T cell-based immunotherapy is the development of tumor immune
      escape variants. Using our previously reported CMS5 tumor/DUC18 CD8(+) TCR
      transgenic system, we sought to investigate whether large established tumors can
      be successfully eliminated before the development of escape variants. Using
      BALB/c mice that were s.c. transplanted with two tumors that had been growing for
      8 days (double 8-day tumors), we assessed the in vivo anti-tumor activity of in
      vitro peptide-stimulated DUC18 T cells. A single infusion of activated DUC18 T
      cells showed a modest effect against the double 8-day tumors, whereas two and
      three administrations led to regression of both tumors within 10 days. However,
      in some mice, the tumors re-grew approximately 10 days after the regression. We
      found these tumors to be antigen-loss variants. These relapsed tumor cells
      progressively grew in DUC18 transgenic mice and did not express tERK-specific
      message. When four doses of activated DUC18 T cells were infused, the double 8
      day tumors were successfully eliminated and the tumors did not grow out in any
      mice. Our results demonstrate that mono-specific CD8(+) T cells can effectively
      eliminate large established tumors before the development of antigen-loss
      variants when a high number of T cells is rapidly administered.

PMID- 12807819
TI  - A truncated IFN-regulatory factor-8?IFN consensus sequence-binding protein acts
      as dominant-negative, interferes with endogenous protein-protein interactions and
      leads to apoptosis of immune cells.
AB  - IFN consensus sequence-binding protein (ICSBP) is a member of the IFN-regulatory
      factors (IRF) and is thus also called IRF-8. Its expression is restricted to
      hematopoietic cells and IRF-8?ICSBP(-/-) mice are defective in myeloid cell
      differentiation. This factor exerts its transcriptional activity through
      interaction with other transcription factors, which leads to either repression or
      activation. In this paper, we describe the use of a dominant-negative (DN) mutant
      of IRF-8?ICSBP designed to serve as a molecular tool to dissociate the role of
      the various protein-protein interactions. This DN-ICSBP is truncated at the DNA
      binding domain and can still associate with other factors, but the
      heterocomplexes produced are incapable of binding to the DNA. We show that the DN
      ICSBP is able to compete for the interaction of IRF-8?ICSBP with either IRF or
      non-IRF members such as PU.1. Accordingly, this DN construct was able to inhibit
      the PU.1-dependent expression of the IgLlambda in the plasmacytoma cell line
      J558L. However, stable expression of this DN-ICSBP led to apoptosis of only
      hematopoietic cells. The data suggests that DN-ICSBP can form heterocomplexes
      with an as-yet unidentified survival factor for hematopoietic cells.

PMID- 12807820
TI  - CD154-CD40-independent up-regulation of B7-2 on splenic antigen-presenting cells
      and efficient T cell priming by staphylococcal enterotoxin A.
AB  - It has been demonstrated that in vivo T cell priming requires CD154-CD40
      interaction, which is suggested to be critical in the induction of co-stimulatory
      activities on antigen-presenting cells (APC). In the current study, we
      demonstrate that in vivo administration of a high dose of a superantigen,
      staphylococcal enterotoxin A (SEA), could up-regulate B7-2 on most splenic APC
      independently of the CD154-CD40 interaction, followed by efficient expansion of
      SEA-reactive V(beta)3(+) T cells in CD154- or CD40-deficient mice. However, the
      CD154-CD40 interaction may be involved in SEA-mediated T cell activation, since a
      contribution of the CD154-CD40 interaction was observed when a lower dose of SEA
      was injected. CD154-independent T cell priming by SEA appeared also independent
      of the TRANCE-RANK pathway, which was shown to be capable of mediating CD154
      independent activation of naive T cells during the infection of some viruses.
      These results indicate that SEA, which provokes rapid and efficient T cell
      responses without adjuvant, could utilize multiple CD154/TRANCE-independent
      pathways, to prime T cells.

PMID- 12807821
TI  - Phosphodiesterase 4 inhibitors reduce human dendritic cell inflammatory cytokine
      production and Th1-polarizing capacity.
AB  - Inhibitors of cAMP-specific phosphodiesterase (PDE) 4 have been shown to inhibit
      inflammatory mediator release and T cell proliferation, and are considered
      candidate therapies for T(h)1-mediated diseases. However, little is known about
      how PDE4 inhibitors influence dendritic cells (DC), the cells responsible for the
      priming of naive T(h) cells. Therefore, we investigated the PDE profile of
      monocyte-derived DC, and whether PDE4 inhibitors modulate DC cytokine production
      and T cell-polarizing capacity. We mainly found cAMP-specific PDE4 enzymatic
      activity in both immature and mature DC. In contrast to monocytes that mainly
      express PDE4B, we found that PDE4A is the predominant PDE4 subtype present in DC.
      Immature DC showed reduced ability to produce IL-12p70 and tumor necrosis factor
      (TNF)-alpha upon lipopolysaccharide or CD40 ligand (CD40L) stimulation in the
      presence of PDE4 inhibitors, whereas cytokine production upon CD40L stimulation
      of fully mature DC in the presence of PDE4 inhibitors was not affected. Exposure
      to PDE4 inhibitors for 2 days during DC maturation did not influence T cell
      stimulatory capacity or acquisition of a mature phenotype, but increased the
      expression of the chemokine receptor CXCR4. Furthermore, DC matured in the
      presence of PDE4 inhibitors showed reduced capacity to produce IL-12p70 and TNF
      alpha upon subsequent CD40L stimulation. Using these PDE4 inhibitor-matured DC to
      stimulate naive T cells resulted in a reduction of IFN-gamma-producing (T(h)1)
      cells. These findings indicate that PDE4 inhibitors can affect T cell responses
      by acting at the DC level and may increase our understanding of the therapeutic
      implication of PDE4 inhibitors for T(h)1-mediated disorders.

PMID- 12807822
TI  - A novel tumor-vaccine cell therapy using bone marrow-derived dendritic cell type
      1 and antigen-specific Th1 cells.
AB  - Dendritic cell (DC)-based tumor-vaccine therapy is a rational strategy for tumor
      immunotherapy. However, using this protocol, it is still difficult to induce long
      term regression in established tumor-bearing mice. To overcome this problem we
      developed a novel tumor-vaccine therapy, combining inactivated tumor cells with
      bone marrow-derived DC type 1 (BMDC1) and antigen-specific T(h)1 cells. BALB/c
      mice were intradermally inoculated with A20-OVA tumor cells expressing ovalbumin
      (OVA) as a model tumor antigen. After A20-OVA tumor mass became palpable (6-8
      mm), mice were treated with DC-based vaccine therapy in various protocols. A
      complete cure of tumor-bearing mice was induced only when mice were repeatedly
      vaccinated with inactivated A20-OVA cells, OVA-pulsed BMDC1 and OVA-specific
      T(h)1 cells. Regression of tumor cells was associated with induction of
      T(h)1/T(c)1-dominant antitumor immunity. Removal of one of these cellular
      components during vaccination resulted in failure to completely cure tumor
      bearing mice. Moreover, BMDC2 cells could not replace the therapeutic effect of
      BMDC1 cells combined with T(h)1 cells. Thus, we propose a novel tumor-vaccine
      cell therapy using DC1 and T(h)1 cells.

PMID- 12807823
TI  - Bovine IgM antibodies with exceptionally long complementarity-determining region
      3 of the heavy chain share unique structural properties conferring restricted VH
      + Vlambda pairings.
AB  - Naturally occurring antibody repertoires of cattle (Bos taurus) include a group
      of IgMlambda antibodies with exceptionally long complementarity-determining
      region 3 of the heavy chain (CDR3H) segments, containing multiple Cys residues.
      These massive CDR3H segments will greatly influence the tertiary and quaternary
      structures of the bovine IgM combining sites. As an antibody's combining site is
      formed by both heavy and light chains, we have analyzed the nucleotide sequences
      and structural properties of the lambda-light chains that pair with micro -heavy
      chains containing exceptionally long CDR3H. There appears to be an exquisite
      selective pressure for the use of three V(lambda)1 genes (V(lambda)1x and two new
      V(lambda)1d and V(lambda)1e genes) in IgM with unusually long CDR3H. The
      V(lambda)1d and V(lambda)1e genes are similar to each other, but diverge from the
      other V(lambda)1 genes into two closely related subfamilies. The available bovine
      V(lambda) genes are classified into three V(lambda) gene families: V(lambda)1,
      V(lambda)2 and V(lambda)3 based on nucleotide similarity >/=80%. Further,
      analysis of total Ser content and positions of Ser residues in the sequences was
      found to be sufficient to classify the cattle V(lambda)1 subfamilies. Patterns of
      Ser residues differ for V(lambda) domains from ruminant species (e.g. cattle,
      sheep and goats) and other mammals (e.g. humans and mice). These 'Ser signatures'
      can be used to track divergent evolution in lambda-light chains. Interestingly,
      Ser90L in complementarity-determining region 3 of the light chain (CDR3L)
      occurred in all V(lambda) domains that pair with V(H) regions containing
      exceptionally long CDR3H. A structural role for Ser90L was revealed in homology
      models of V(lambda) domains, i.e. to hold the ascending polypeptide of CDR3L in a
      relatively tight space between the N-terminal segment and residues from CDR1L.
      The CDR3L of V(lambda) domains also occupied smaller volumes if paired to V(H)
      domains with extremely long CDR3H (>/=48 residues), and were more variable in
      their conformation and filled larger volumes if CDR3Hs were </=22 residues. Thus,
      the role of the lambda-light chains in these unusual cattle antibodies is
      probably to act as a relatively featureless supporting platform for the extremely
      long CDR3H regions, which undoubtedly are dominantly involved in binding to an
      antigen.

PMID- 12807824
TI  - Protection from autoimmune brain inflammation in mice lacking IFN-regulatory
      factor-1 is associated with Th2-type cytokines.
AB  - IFN-regulatory factor-1 (IRF-1) is a transcription factor that regulates the
      expression of IFN-induced genes and type I IFN. It has previously been
      demonstrated that IRF-1-deficient mice show reduced susceptibility to
      experimental autoimmune encephalomyelitis (EAE) induced by a peptide from myelin
      basic protein. To further study the role of IRF-1 in brain inflammation, we
      analyzed EAE induced by immunization with a myelin oligodendrocyte glycoprotein
      derived peptide in 129/Sv mice lacking IRF-1. We found that these mice were
      almost completely resistant to EAE induction and that this unresponsiveness was
      intrinsically related to the IRF-1 deficiency of the T cells, but not with any
      other cell type. Furthermore, we show that the amelioration of EAE was associated
      with increased production of T(h)2-type and decreased production of T(h)1-type
      cytokines. These results demonstrate that absence of IRF-1 in myelin-specific T
      cells results in protection from severe EAE and is associated with a skewing of
      the T cell response towards T(h)2.

PMID- 12807825
TI  - LIGHT-deficiency impairs CD8+ T cell expansion, but not effector function.
AB  - LIGHT, a newly identified member of the tumor necrosis factor (TNF) family, is
      expressed on activated T lymphocytes. To evaluate how LIGHT contributes to T cell
      functions, we generated LIGHT-deficient (LIGHT(-/-)) mice using gene targeting.
      Disruption of LIGHT significantly reduced CD8(+) T cell-cycle progression,
      leading to reduced proliferation to anti-CD3, anti-CD3/anti-CD28 or allogeneic
      stimulation, whereas proliferation of CD4(+) T cells remained unchanged. In
      contrast to the observed proliferative defects, isolated CD8(+) T cells from
      LIGHT(-/-) mice displayed normal cytotoxic effector function development when
      compared to wild-type CD8(+) T cells. Underlying a potential mechanism of reduced
      CD8(+) T cell proliferation, LIGHT(-/-) CD8(+) T cells displayed reduced surface
      levels of CD25 and a diminished ability to proliferate in response to exogenous
      IL-2. Furthermore, addition of IL-12 to LIGHT(-/-) CD8(+) T cell cultures could
      not ameliorate this proliferative defect. These results reveal a potential
      mechanism of action for LIGHT as a positive regulator of CD8(+) T cell expansion,
      but not lytic effector function development.

PMID- 12807826
TI  - Why are there so few key mutant clones? The influence of stochastic selection and
      blocking on affinity maturation in the germinal center.
AB  - A small number of key somatic mutations lead to high-affinity binding in the anti
      hapten immune responses to 2-phenyl-5-oxazolone (phOx) and (4-hydroxy-3
      nitrophenyl)acetyl (NP). Affinity maturation models of the germinal center hold
      that B cells carrying these key mutations are preferentially selected for
      expansion within the germinal centers. However, additional factors are required
      to account for some quantitative aspects of affinity maturation in vivo.
      Radmacher et al. have shown that key mutants are observed in vivo significantly
      less frequently than expected by these models. To account for this finding, they
      propose that selection is a stochastic process where key mutants may be
      overlooked by positive selection or recruited out of the germinal center. While
      acknowledging that a minimal amount of stochastic selection is probably
      unavoidable in the germinal center, we instead propose a structural explanation
      for this key mutant discrepancy. This model is based on the existence of a large
      number of blocking mutations whose presence can prevent the ability of key
      mutations to confer high-affinity binding. Using mathematical modeling and
      computer simulation, we show that in addition to reconciling the key mutant
      discrepancy, the blocking model accounts for other aspects of experimental data
      that are not predicted by the stochastic selection model. In particular, the
      blocking model is consistent with the observation that key mutants generally
      exhibit a higher number of mutations per sequence in the phOx response, but a
      lower number in the NP response.

PMID- 12807827
TI  - Effector T cells have a lower ligand affinity threshold for activation than naive
      T cells.
AB  - It has been previously established that effector and memory T cells are more
      sensitive to antigen stimulation than naive T cells. In this study, we compared
      the effect of ligand affinity on the activation of naive and effector T cells
      derived from pigeon cytochrome c (PCC)-specific TCR transgenic mice by
      stimulating these cells with a variety of ligands with widely differing
      antigenicity. The data obtained indicated the following. (i) The differences in
      antigen dose requirements for activation of naive and effector cells widened as
      the affinity of the antigen decreased. Most dramatically, peptides that were TCR
      antagonists for naive T cells were recognized as agonists by effector T cells.
      (ii) While both naive and effector T cells were activated by the bacterial
      superantigen staphylococcal enterotoxin A, specific for the transgenic TCR
      V(beta)3 chain, effector, but not naive, T cells were stimulated to proliferate
      by toxic shock syndrome toxin-1, a superantigen not previously described to be
      stimulatory for V(beta)3 T cells. (iii) Effector T cells, but not naive cells,
      proliferated in response to endogenous self-peptides presented by antigen
      presenting cells in a syngeneic mixed lymphocyte reaction. Taken together these
      data indicate that effector T cells have a lower affinity threshold for
      activation than naive T cells. Further studies demonstrated that the heightened
      reactivity of effector T cells to low-affinity ligands declined progressively
      with repeated stimulations by antigen such that after repeated stimulation
      effector T cells were no longer stimulated by low-affinity ligands but recognized
      them as TCR antagonists similar to naive T cells.

PMID- 12807828
TI  - The Edinburgh heart valve study.

PMID- 12807830
TI  - Invasive assessment of myocardial bridges.

PMID- 12807831
TI  - Assessing perfusion and function in acute myocardial infarction: how and when?

PMID- 12807832
TI  - Area ablation of ventricular tachycardia in a patient with arrhythmogenic right
      ventricular cardiomyopathy.

PMID- 12807833
TI  - The "ultrasonic stethoscope": is it of clinical value?

PMID- 12807834
TI  - The "pop phenomenon" detected by phased array intracardiac echocardiography.

PMID- 12807835
TI  - B Type natriuretic peptide: a good omen in myocardial ischaemia?

PMID- 12807837
TI  - Risk of competitive sport in young athletes with heart disease.
AB  - The majority of sudden deaths in young athletes occur in the context of
      underlying inherited or genetic cardiac disorders. The evaluation of every
      athlete regarding underlying cardiac disease is impractical and therefore needs
      to be targeted at those who are at a higher risk. A practical approach would be
      to channel efforts towards athletes with cardiac symptoms, those with a family
      history of inherited cardiac disease, and those with a family history of
      premature sudden death. There are potential pitfalls in the evaluation of young
      athletes using non-invasive tests when making the distinction between
      physiological adaptations to exercise and cardiac pathology. Physicians
      evaluating young athletes need to be aware of the spectrum of physiological
      adaptations and to be familiar with conditions responsible for sudden death in
      this population.

PMID- 12807838
TI  - Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine
      bioprostheses.
AB  - OBJECTIVE: To compare survival and outcome in patients receiving a mechanical or
      bioprosthetic heart valve prosthesis. DESIGN: Randomised prospective trial.
      SETTING: Tertiary cardiac centre. PATIENTS: Between 1975 and 1979, patients were
      randomised to receive either a Bjork-Shiley or a porcine prostheses. The mitral
      valve was replaced in 261 patients, the aortic in 211, and both valves in 61
      patients. Follow up now averages 20 years. MAIN OUTCOME MEASURES: Death,
      reoperation, bleeding, embolism, and endocarditis. RESULTS: After 20 years there
      was no difference in survival (Bjork-Shiley v porcine prosthesis (mean (SEM)):
      25.0 (2.7)% v 22.6 (2.7)%, log rank test p = 0.39). Reoperation for valve failure
      was undertaken in 91 patients with porcine prostheses and in 22 with Bjork-Shiley
      prostheses. An analysis combining death and reoperation as end points confirmed
      that Bjork-Shiley patients had improved survival with the original prosthesis
      intact (23.5 (2.6)% v 6.7 (1.6)%, log rank test p < 0.0001); this difference
      became apparent after 8-10 years in patients undergoing mitral valve replacement,
      and after 12-14 years in those undergoing aortic valve replacement. Major
      bleeding was more common in Bjork-Shiley patients (40.7 (5.4)% v 27.9 (8.4)%
      after 20 years, p = 0.008), but there was no significant difference in major
      embolism or endocarditis. CONCLUSIONS: Survival with an intact valve is better
      among patients with the Bjork-Shiley spherical tilting disc prosthesis than with
      a porcine prosthesis but there is an attendant increased risk of bleeding.

PMID- 12807839
TI  - Carbohydrates, dietary glycaemic load and glycaemic index, and risk of acute
      myocardial infarction.
AB  - OBJECTIVES: To assess the relation between selected carbohydrate foods, dietary
      glycaemic load and glycaemic index, and the risk of non-fatal acute myocardial
      infarction in a population with a high intake of refined carbohydrates. DESIGN
      AND SETTING: Hospital based case-control study conducted in Milan, Italy, between
      1995 and 1999. PATIENTS: 433 non-diabetic subjects with a first episode of non
      fatal acute myocardial infarction, and 448 controls admitted to hospital for a
      wide spectrum of acute conditions unrelated to known or potential risk factors
      for acute myocardial infarction. METHODS: Information was collected by
      interviewer administered questionnaires. Multivariate odds ratios (OR) and 95%
      confidence intervals (CI) were obtained by multiple logistic regression models.
      RESULTS: Compared with patients in the lowest tertile of intake, the multivariate
      OR for those in the highest tertile was 1.00 for bread, 1.27 for pasta and rice,
      1.38 for soups, 0.78 for potatoes, 0.97 for desserts, and 1.00 for sugar. The OR
      for the highest tertile of score was 1.08 for glycaemic load and 1.38 for
      glycaemic index. None of the estimates was significant. A significant association
      with acute myocardial infarction risk was found for glycaemic index in patients
      aged > or = 60 years (OR 1.81, 95% CI 1.07 to 3.07 for the highest tertile of
      score compared with the lowest) and in those with a body mass index > or = 25
      kg/m2 (OR 2.02, 95% CI 1.21 to 3.34). CONCLUSIONS: In this Italian population
      high glycaemic load and glycaemic index were not strongly associated with acute
      myocardial infarction risk, but slightly increased odds ratios were observed for
      glycaemic index in elderly people and in association with overweight.

PMID- 12807840
TI  - Right atrial thrombus following closure of an atrial septal defect.

PMID- 12807841
TI  - Clinical utility and cost effectiveness of a personal ultrasound imager for
      cardiac evaluation during consultation rounds in patients with suspected cardiac
      disease.
AB  - OBJECTIVE: To assess the clinical utility and cost effectiveness of a personal
      ultrasound imager (PUI) during consultation rounds for cardiac evaluation of
      patients with suspected cardiac disease. METHODS: 107 unselected patients from
      non-cardiac departments (55% men) were enrolled in the study. After the physical
      examination the consultant cardiologist performed an echocardiographic study with
      a PUI. The final report was given instantly to the referring physician. All
      patients subsequently underwent a study with a standard echocardiographic device
      (SED). For each patient the consultant cardiologist noted whether the findings of
      the PUI were adequate for final diagnosis. The total cost when full
      echocardiography was used was compared with the cost when the PUI was used. The
      time interval from request to diagnosis was also compared. RESULTS: In 84 (78.5%)
      patients no further examination with an SED was regarded as necessary. Twenty
      three patients (21.5%) required a further detailed examination with the SED
      because of the need for haemodynamic information. There was an excellent
      agreement for the detection of abnormalities between the two devices (96%). The
      total cost was euro;132 per patient with the SED and euro;75 per patient with the
      PUI. According to this study, the use of the PUI can lead to a 33.4% reduction of
      total cost. The mean time from request to diagnosis at the authors' institution
      was four days for the SED and instantly for the PUI, for additional potential
      cost savings. CONCLUSIONS: Immediate echocardiographic assessment during
      consultation rounds can lead to significant cost savings and can shorten the time
      to diagnosis.

PMID- 12807842
TI  - Infective endocarditis with progressive periaortal abscess formation in a
      previously healthy girl.

PMID- 12807843
TI  - Temporal evolution and functional outcome of no reflow: sustained and
      spontaneously reversible patterns following successful coronary recanalisation.
AB  - OBJECTIVE: To identify in humans the temporal patterns of no reflow and their
      functional implications. METHODS: 24 patients with first acute myocardial
      infarction and successful coronary recanalisation by recombinant tissue-type
      plasminogen activator (n = 15) or primary percutaneous transluminal coronary
      angioplasty (n = 9) were studied by myocardial contrast echocardiography within
      24 hours of recanalisation and at one month's follow up. Myocardial contrast
      echocardiography was performed by intermittent harmonic power Doppler and
      intravenous Levovist. The regional contrast score index (CSI) was calculated
      within dysfunctioning myocardium. Videointensity was measured (dB) within risk
      and control areas and their ratio was calculated. RESULTS: In 8 patients reflow
      was observed at 24 hours and persisted at one month. Conversely in 16 patients
      areas of no reflow were detectable at 24 hours. At one month, no reflow was
      spontaneously reversible in 9 patients (mean (SD) CSI and videointensity ratio
      improved from 2.5 (0.5) to 1.4 (0.6) and from 0.6 (0.1) to 0.7 (0.1),
      respectively; p < 0.05) and was sustained in the remaining 7 patients (CSI and
      videointensity ratio remained unchanged from 2.6 (0.6) to 2.6 (0.5) and from 0.5
      (0.2) to 0.5 (0.2), respectively; NS). Left ventricular function improved
      significantly in patients with reflow and reversible no reflow. Volumes were
      enlarged only in patients with sustained no reflow. CONCLUSIONS: No reflow
      detected at 24 hours may be sustained or spontaneously reversible at one month.
      Such reversibility of the phenomenon is associated with preserved left
      ventricular volumes and function. Clarification of the mechanisms of delayed
      reversibility may lead to tailored treatment of no reflow even in the subacute
      phase of myocardial infarction.

PMID- 12807844
TI  - Transcatheter embolisation of a large unilateral pulmonary arteriovenous
      malformation.

PMID- 12807846
TI  - Coronary arterial sling operation.

PMID- 12807845
TI  - Detection of scarred and viable myocardium using a new magnetic resonance imaging
      technique: blood oxygen level dependent (BOLD) MRI.
AB  - BACKGROUND: The identification of viable myocardium in patients with impaired
      left ventricular contraction secondary to coronary heart disease is important
      clinically as such myocardium is likely to benefit from revascularisation. Blood
      oxygen level dependent (BOLD) magnetic resonance imaging (MRI) relies on changes
      in deoxyhaemoglobin concentration under stress for signal generation and could be
      used for the differentiation between scarred and viable myocardium. AIM: To
      assess the signal change on BOLD MRI in viable and scarred myocardium as
      identified by positron emission tomography (PET). METHOD: 19 patients with
      impaired left ventricular contraction and at least one akinetic area were
      enrolled. They underwent rest and dipyridamole stress MRI, using a double breath
      hold T2* weighted, ECG gated sequence to produce BOLD contrast images, and cine
      MRI for wall thickening assessment. Dynamic perfusion and metabolic PET images
      followed the MRI. Signal change on BOLD MRI and the wall thickening were compared
      between rest and stress images in hibernating and scarred segments identified by
      PET on two short axis slices of mid ventricle, with eight segments each. RESULTS:
      Using PET, 68 segments were identified as hibernating and 42 as scarred. The
      hibernating segments were found on BOLD MRI to have an average signal change
      between rest and stress of -9.53%, compared with -2.15% in the scarred segments
      (p = 0.008). The average wall thickening was 8.7 mm in the hibernating segments
      compared with 5.9 mm in the scarred segments (p < 0.0001). CONCLUSIONS: BOLD MRI
      with wall thickening may differentiate scarred and viable myocardium and help
      identify suitable patients for revascularisation. Further larger studies are
      needed to establish a threshold for detection, sensitivity, and specificity.

PMID- 12807847
TI  - The influence of age, sex and other variables on the plasma level of N-terminal
      pro brain natriuretic peptide in a large sample of the general population.
AB  - OBJECTIVE: To identify potentially confounding variables for the interpretation
      of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). DESIGN: Randomly
      selected subjects filled in a heart failure questionnaire and underwent pulse and
      blood pressure measurements, ECG, echocardiography, and blood sampling. SETTING:
      Subjects were recruited from four Copenhagen general practices located in the
      same urban area and were examined in a Copenhagen University Hospital. PATIENTS:
      382 women and 290 men in four age groups: 50-59 years (n = 174); 60-69 years (n =
      204); 70-79 years (n = 174); and > 80 years (n = 120). MAIN OUTCOME MEASURES:
      Associations between the plasma concentration of NT-proBNP and a range of
      clinical variables. RESULTS: In the undivided study sample, female sex (p <
      0.0001), greater age (p < 0.0001), increasing dyspnoea (p = 0.0001), diabetes
      mellitus (p = 0.01), valvar heart disease (p = 0.002), low heart rate (p <
      0.0001), left ventricular ejection fraction < or = 45% (p < 0.0001), abnormal ECG
      (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma
      glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p <
      0.0001) were independently associated with a high plasma log10[plasma NT-proBNP]
      by multiple linear regression analysis. CONCLUSIONS: A single reference interval
      for the normal value of NT-proBNP is unlikely to suffice. There are several
      confounders for the interpretation of a given NT-proBNP concentration and at the
      very least adjustment should be made for the independent effects of age and sex.

PMID- 12807848
TI  - Different presentation of hypertrophic cardiomyopathy in monozygotic twins.

PMID- 12807849
TI  - Pregnancy related complications in women with hypertrophic cardiomyopathy.
AB  - OBJECTIVES: To determine whether pregnancy is well tolerated in hypertrophic
      cardiomyopathy. SETTING: Referral clinic. DESIGN: The study cohort comprised 127
      consecutively referred women with hypertrophic cardiomyopathy. Forty (31.5%)
      underwent clinical evaluation before pregnancy. The remaining 87 (68.5%) were
      referred after their first pregnancy. All underwent history, examination,
      electrocardiography, and echocardiography. Pregnancy related symptoms and
      complications were determined by questionnaire and review of medical and
      obstetric records where available. RESULTS: There were 271 pregnancies in total.
      Thirty six (28.3%) women reported cardiac symptoms in pregnancy. Over 90% of
      these women had been symptomatic before pregnancy. Symptoms deteriorated during
      pregnancy in fewer than 10%. Of the 36 women with symptoms during pregnancy, 30
      had further pregnancies. Symptoms reoccurred in 18 (60%); symptomatic
      deterioration was not reported. Heart failure occurred postnatally in two women
      (1.6%). No complications were reported in 19 (15%) women who underwent general
      anaesthesia and in 22 (17.4%) women who received epidural anaesthesia, three of
      whom had a significant left ventricular outflow tract gradient at diagnosis after
      pregnancy. Three unexplained intrauterine deaths occurred in women taking cardiac
      medication throughout pregnancy. No echocardiographic or clinical feature was a
      useful indicator of pregnancy related complications. CONCLUSIONS: Most women with
      hypertrophic cardiomyopathy tolerate pregnancy well. However, rare complications
      can occur and therefore planned delivery and fetal monitoring are still required
      for some patients.

PMID- 12807850
TI  - Progression of familial and non-familial dilated cardiomyopathy: long term follow
      up.
AB  - BACKGROUND: It is unknown whether progression of familial idiopathic dilated
      cardiomyopathy differs from progression in the non-familial form. It has been
      suggested that familial disease indicates a worse prognosis, and that this should
      be considered when planning the timing of heart transplantation. OBJECTIVE: To
      compare five year survival or time to heart transplantation in an unselected
      series of patients with dilated cardiomyopathy who had been evaluated for
      familial v non-familial disease through the echocardiographic investigation of
      first degree relatives. DESIGN: Medical records were reviewed and questionnaires
      were mailed to all patients who had previously participated in a family based
      study of dilated cardiomyopathy. Information was gathered about survival, heart
      transplantation, and left ventricular ejection fraction (LVEF) measurements.
      Survival data were censored at the time of cardiac transplantation. RESULTS:
      Follow up data were obtained for 99 of 101 patients (69 with non-familial and 30
      with familial disease). Five year survival was 55% for non-familial and 51% for
      familial patients (NS). The main predictor of mortality was an LVEF of < 30%.
      Familial status did not predict mortality. There was no significant difference in
      follow up LVEF values between the groups. CONCLUSIONS: Five year survival is not
      significantly different in the familial and non-familial forms of dilated
      cardiomyopathy.

PMID- 12807851
TI  - Partial anomalous pulmonary venous connection or scimitar syndrome.

PMID- 12807852
TI  - Left ventricular remodelling, and systolic and diastolic function in young adults
      with beta thalassaemia major: a Doppler echocardiographic assessment and
      correlation with haematological data.
AB  - OBJECTIVE: To evaluate left ventricular morphology and function in a large
      population of patients with beta thalassaemia. DESIGN: Echo Doppler assessment of
      left ventricular function and correlation of cardiovascular data with
      haematological data. SETTING: Thalassaemia unit in a tertiary referral centre.
      PATIENTS: 197 young adults with beta thalassaemia, following an adequate
      transfusional and chelation treatment regimen, without clinical signs of
      cardiopulmonary involvement. The control group consisted of 213 healthy subjects.
      RESULTS: Left ventricular volumes, mass index, and mass/volume ratio were
      increased. Diastolic and systolic shapes were different, the left ventricle
      maintaining an ellipsoidal shape. The ejection fraction was reduced, and was <
      50% in 33 patients. Stroke volume and cardiac index were increased, and systemic
      vascular resistance was decreased. Fractional shortening and mean velocity of
      circumferential shortening were decreased. Meridional end systolic and peak
      systolic stress were increased, as was circumferential end systolic stress. The
      contractile state was reduced while the functional preload index did not differ.
      Left ventricular diastolic function, evaluated from the mitral inflow, showed a
      slightly prolonged isovolumic relaxation time, increased flow velocity integrals,
      and an increased E/A ratio. Among the haematological data, only serum ferritin
      showed a weak negative correlation with left ventricular ejection fraction. The
      patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection
      fraction. CONCLUSIONS: Patients with beta thalassaemia on an adequate transfusion
      and chelation treatment regimen show abnormal left ventricular remodelling with
      increased volumes, mass, and mass/volume ratio. Systolic chamber function and
      contractile state are reduced, with a slightly increased afterload. These
      findings seem mainly to be related to the increased cardiac output caused by
      chronic anaemia. Left ventricular performance is better preserved when chelation
      treatment is adjusted to maintain the serum ferritin concentration at < 1000
      ng/ml.

PMID- 12807853
TI  - Adverse events in coronary artery bypass graft (CABG) trials: a systematic review
      and analysis.
AB  - OBJECTIVES: To quantify the incidence of major adverse events (AEs) occurring in
      hospital or within 30 days after surgery in patients undergoing coronary artery
      bypass graft (CABG) surgery and to identify risk factors for these AEs. METHODS:
      Systematic review and analysis of studies published in English since 1990.
      Studies of isolated standard CABG reporting postoperative incidence of myocardial
      infarction (MI), stroke, gastrointestinal bleeding, renal failure, or death in
      hospital or within 30 days were eligible for inclusion. Incidence of these events
      was calculated overall and for selected patient groups defined by all elective
      CABG versus mixed (some non-elective); mean ejection fraction < or = 50% versus >
      50%; mean age < or= 60 versus > 60 years; primary CABG versus some reoperations;
      randomised controlled trials versus cohort studies; and single centre versus
      multicentre studies. Odds ratios of selected AEs were computed according to group
      risk factors. RESULTS: 176 studies (205 717 patients) met all inclusion criteria.
      The average incidence of major AEs occurring in-hospital was death (1.7%); non
      fatal MI (2.4%); non-fatal stroke (1.3%); gastrointestinal bleeding (1.5%); and
      renal failure (0.8%). Thirty day mortality was 2.1%. Meta-analyses show that age
      > 70, female sex, low ejection fraction, history of stroke, MI, or heart surgery,
      and presence of diabetes or hypertension are all associated with increased 30 day
      mortality after CABG. CONCLUSION: The incidence of major AEs in patients after
      CABG varies widely across studies and patient populations, and this heterogeneity
      must be controlled when using the literature to benchmark safety.

PMID- 12807854
TI  - Transcatheter closure of large fistula between left main coronary artery and
      right atrium using Amplatzer duct occluder.

PMID- 12807855
TI  - High preprocedural non-HDL cholesterol is associated with enhanced oxidative
      stress and monocyte activation after coronary angioplasty: possible implications
      in restenosis.
AB  - OBJECTIVE: To investigate whether enhanced oxidant stress in patients undergoing
      percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher
      concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and
      whether this contributes to the inflammatory reaction and luminal renarrowing
      after PTCA. DESIGN: An ex vivo and in vitro study of 46 patients who underwent
      PTCA and who had repeat angiograms after six months. Blood samples were collected
      immediately before PTCA, and at 24 hours, 48 hours, and 15 days after. SETTING:
      Tertiary referral centre. SUBJECTS: 46 patients (30 male, 16 female; mean (SD)
      age, 62 (5) years) with stable or unstable angina who underwent elective PTCA.
      MAIN OUTCOME MEASURES: Continuous variable luminal loss as defined by change in
      minimum lumen diameter during follow up, normalised for vessel size; lag phase of
      low density lipoprotein to in vitro oxidation; plasma fluorescent products of
      lipid peroxidation (FPLP); plasma vitamin C and E; interleukin (IL) 1beta
      secretion from unstimulated monocytes; plasma C reactive protein (CRP). RESULTS:
      Restenosis occurred in 12 patients (26%). Oxidant stress after PTCA was greater
      (p < 0.0001 at 15 days) in the patients with restenosis and showed a significant
      correlation with the preprocedural concentration of non-HDL cholesterol (p <
      0.001). Inflammatory reaction (as reflected by IL-1beta production and CRP) and
      late lumen loss were linearly correlated (p < 0.001) with lag phase and FPLP
      throughout the study, and inversely (p < 0.05) with vitamin C and E measured at
      two and 15 days after PTCA. CONCLUSIONS: This study provides evidence for the
      critical role of cholesterol dependent oxidant stress in the pathophysiology of
      restenosis after PTCA. The findings raise the possibility that drugs capable of
      modulating oxidant status might provide a novel form of adjuvant treatment in
      patients with hypercholesterolaemia undergoing PTCA.

PMID- 12807856
TI  - Pericardial effusion after open heart surgery for congenital heart disease.
AB  - OBJECTIVES: To determine the prevalence and time course of pericardial effusion
      after open heart surgery for congenital heart diseases and to identify
      predisposing risk factors. DESIGN AND PATIENTS: Prospective assessment of
      development of pericardial effusion in 336 patients (163 males) undergoing open
      heart surgery for congenital heart disease by serial echocardiography on days 5,
      7, 14, 21, and 28 postoperatively. SETTING: Tertiary paediatric cardiac centre.
      RESULTS: The prevalence of pericardial effusion was 23% (77 of 336). Of the 77
      patients who developed effusion, 43 (56%) had moderate to large effusions and 18
      (23%) were symptomatic. Patients who had a large amount of effusion were more
      likely to be symptomatic than those with only a small to moderate amount (47.4% v
      15.5%, p = 0.01). The mean (SD) onset of pericardial effusion was 11 (7) days
      after surgery, with 97% (75 of 77) of cases being diagnosed on or before day 28
      after surgery. The prevalence of effusion after Fontan-type procedures (60%, 6 of
      10) was significantly higher than that after other types of cardiac surgery:
      repair of left to right shunts (22.1%, 43 of 195), repair of lesions with right
      ventricular outflow tract obstruction (22.6%, 19 of 84), arterial switch
      operation (6.7%, 1 of 15), and miscellaneous procedures (25%, 8 of 32) (p =
      0.037). Univariate analyses showed that female patients (p = 0.009) and those
      receiving warfarin (p = 0.002) had increased risk of postoperative pericardial
      effusion. A greater pericardial drain output in the first four hours after
      surgery also tended to be significant (p = 0.056). Multivariate logistic
      regression similarly identified warfarin treatment (beta = 1.73, p = 0.009) and
      female sex (beta for male = -0.63, p = 0.037) as significant determinants.
      CONCLUSIONS: Pericardial effusion occurs commonly after open heart surgery for
      congenital heart disease. Serial echocardiographic monitoring up to 28 days
      postoperatively is indicated in selected high risk patients such as those with
      symptoms of postpericardiotomy syndrome and those given warfarin.

PMID- 12807857
TI  - Pacemaker lead fracture.

PMID- 12807858
TI  - Femoral vein delivery of contrast improves transoesophageal detection of
      intracardiac shunting through a patent foramen ovale.

PMID- 12807859
TI  - The applicability of the Framingham coronary heart disease prediction function to
      black and minority ethnic groups in the UK.

PMID- 12807860
TI  - An audit of the implications of implementing NICE guidance on the use of
      implantable cardioverter-defibrillators.

PMID- 12807861
TI  - Transcardiac and transpulmonary gradients in the putative new cardiovascular
      hormone relaxin.

PMID- 12807862
TI  - Severe pulmonary hypertension in a patient with hypertrophic cardiomyopathy:
      response to alcohol septal ablation.

PMID- 12807863
TI  - Cardiac abnormalities in patients with Leber's hereditary optic neuropathy.

PMID- 12807864
TI  - HIV and cardiovascular medicine.

PMID- 12807865
TI  - Calcific aortic stenosis: from bench to the bedside--emerging clinical and
      cellular concepts.

PMID- 12807866
TI  - Development of the heart: (1) formation of the cardiac chambers and arterial
      trunks.

PMID- 12807868
TI  - Persisting fever in a patient with brucella endocarditis: occult splenic abscess.
AB  - Brucella endocarditis, despite its high mortality rate with combined medical and
      surgical treatment, has a low occurrence rate in cases of brucellosis and has
      been endemic in regions surrounding Turkey. Rarely, patients with infective
      endocarditis with common microorganisms develop a splenic abscess. A patient is
      reported on with brucella endocarditis and persistent fever. An occult splenic
      abscess was found. This is the second reported case in the literature of brucella
      endocarditis with splenic abscess.

PMID- 12807869
TI  - ATP uptake in the Golgi and extracellular release require Mcd4 protein and the
      vacuolar H+-ATPase.
AB  - Extracellular nucleotides signal via a large group of purinergic receptors.
      Although much is known about these receptors, the mechanism of nucleotide
      transport out of the cytoplasm is unknown. We developed a functional screen for
      ATP release to the extracellular space and identified Mcd4p, a 919-amino acid
      membrane protein with 14 putative transmembrane domains, as a participant in
      glucose-dependent ATP release from Saccharomyces cerevisiae. This release
      occurred through the vesicular trafficking pathway initiated by ATP uptake into
      the Golgi compartment. Both the compartmental uptake and the extracellular
      release of ATP were regulated by the activity of the vacuolar H+-ATPase. It is
      likely that the Mcd4p pathway is generally involved in non-mitochondrial ATP
      movement across membranes, it is essential for Golgi and endoplasmic reticulum
      function, and its occurrence led to the appearance of P2 purinergic receptors.

PMID- 12807870
TI  - Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter
      pylori-induced NF-kappa B activation and chemokine expression by epithelial
      cells.
AB  - Infection with Helicobacter pylori, a Gram-negative, microaerophilic, flagellated
      bacteria that adheres to human gastric mucosa, is strongly associated with
      gastric ulcers and adenocarcinoma. The mechanisms through which gastric
      epithelial cells recognize this organism are unclear. In this study we evaluated
      the interactions between the Toll-like receptors (TLRs) and H. pylori-mediated NF
      kappa B activation and the induction of chemokine mRNA expression. By reverse
      transcriptase-PCR we determined that MKN45 gastric epithelial cells express low
      but detectable amounts of TLR2, -4, and -5 but no MD-2. To determine which, if
      any, TLRs may play a role in the response of epithelial cells to H. pylori,
      HEK293 cells were cotransfected with the NF-kappa B-Luc reporter, CD14 and MD2
      expression plasmids, and expression plasmids for TLR2, TLR4, or TLR5. Infection
      of the cultures with H. pylori (strain 26695) induced NF-kappa B activity in
      cells transfected with TLR2 and TLR5, but not TLR4. Consistent with the HEK293
      experiments, H. pylori-induced NF-kappa B activation was decreased in MKN45
      gastric epithelial cells by transfection of dominant-negative versions of TLR2
      and TLR5 but not TLR4. Highly purified lipopolysaccharide from H. pylori strain
      26695 activated NF-kappa B in HEK293 via TLR2 but not TLR4. Partially purified
      flagellin from H. pylori was also capable of inducing NF-kappa B activation in
      HEK cells transfected with TLR5. Additionally, chemokine gene expression was
      induced by H. pylori in HEK293 cells following stable transfection with TLR2 or
      TLR5 expression plasmids. These studies demonstrate that gastric epithelial cells
      recognize and respond to H. pylori infection at least in part via TLR2 and TLR5.
      Furthermore, the unique lipopolysaccharide of H. pylori is a TLR2, not a TLR4
      agonist.

PMID- 12807871
TI  - Acquirement of brown fat cell features by human white adipocytes.
AB  - Obesity, i.e. an excess of white adipose tissue (WAT), predisposes to the
      development of type 2 diabetes and cardiovascular disease. Brown adipose tissue
      is present in rodents but not in adult humans. It expresses uncoupling protein 1
      (UCP1) that allows dissipation of energy as heat. Peroxisome proliferator
      activated receptor gamma (PPAR gamma) and PPAR gamma coactivator 1 alpha (PGC-1
      alpha) activate mouse UCP1 gene transcription. We show here that human PGC-1
      alpha induced the activation of the human UCP1 promoter by PPAR gamma. Adenovirus
      mediated expression of human PGC-1 alpha increased the expression of UCP1,
      respiratory chain proteins, and fatty acid oxidation enzymes in human
      subcutaneous white adipocytes. Changes in the expression of other genes were also
      consistent with brown adipocyte mRNA expression profile. PGC-1 alpha increased
      the palmitate oxidation rate by fat cells. Human white adipocytes can therefore
      acquire typical features of brown fat cells. The PPAR gamma agonist rosiglitazone
      potentiated the effect of PGC-1 alpha on UCP1 expression and fatty acid
      oxidation. Hence, PGC-1 alpha is able to direct human WAT PPAR gamma toward a
      transcriptional program linked to energy dissipation. However, the response of
      typical white adipocyte targets to rosiglitazone treatment was not altered by PGC
      1 alpha. UCP1 mRNA induction was shown in vivo by injection of the PGC-1 alpha
      adenovirus in mouse white fat. Alteration of energy balance through an increased
      utilization of fat in WAT may be a conceivable strategy for the treatment of
      obesity.

PMID- 12807872
TI  - Functional analysis of an inosine-guanosine transporter from Leishmania donovani.
      The role of conserved residues, aspartate 389 and arginine 393.
AB  - Equilibrative nucleoside transporters encompass two conserved, charged residues
      that occur within predicted transmembrane domain 8. To assess the role of these
      "signature" residues in transporter function, the Asp389 and Arg393 residues
      within the LdNT2 nucleoside transporter from Leishmania donovani were mutated and
      the resultant phenotypes evaluated after transfection into Delta ldnt2 parasites.
      Whereas an R393K mutant retained transporter activity similar to that of wild
      type LdNT2, the R393L, D389E, and D389N mutations resulted in dramatic losses of
      transport capability. Tagging the wild type and mutant ldnt2 proteins with green
      fluorescent protein demonstrated that the D389N and D389E mutants targeted
      properly to the parasite cell surface and flagellum, whereas the expression of
      R393L at the cell surface was profoundly compromised. To test whether Asp389 and
      Arg393 interact, a series of mutants was generated, D389R/R393R, D389D/R393D, and
      D389R/R393D, within the green fluorescent protein-tagged LdNT2 construct.
      Although all of these ldnt2 mutants were transport-deficient, D389R/R393D
      localized properly to the plasma membrane, while neither D389R/R393R nor
      D389D/R393D could be detected. Moreover, a transport-incompetent D389N/R393N
      double ldnt2 mutant also localized to the parasite membrane, whereas a
      D389L/R393L ldnt2 mutant did not, suggesting that an interaction between residues
      389 and 393 may be involved in LdNT2 membrane targeting. These studies establish
      genetically that Asp389 is critical for optimal transporter function and that a
      positively charged or polar residue at Arg393 is essential for proper expression
      of LdNT2 at the plasma membrane.

PMID- 12807873
TI  - A novel interleukin-17 receptor-like protein identified in human umbilical vein
      endothelial cells antagonizes basic fibroblast growth factor-induced signaling.
AB  - We have previously utilized a combination of high throughput sequencing and
      genome-wide microarray profiling analyses to identify novel cell-surface proteins
      expressed in human umbilical vein endothelial cells. One gene identified by this
      approach encodes a type I transmembrane receptor that shares sequence homology
      with the intracellular domain of members of the interleukin-17 (IL-17) receptor
      family. Real-time quantitative PCR and Northern analyses revealed that this gene
      is highly expressed in human umbilical vein endothelial cells and in several
      highly vascularized tissues such as kidney, colon, skeletal muscle, heart, and
      small intestine. In addition, we also found that it is also highly expressed in
      the ductal epithelial cells of human salivary glands, seminal vesicles, and the
      collecting tubules of the kidney by in situ hybridization. This putative
      receptor, which we have termed human SEF (hSEF), is also expressed in a variety
      of breast cancer tissues. In co-immunoprecipitation assays, this receptor is
      capable of forming homomeric complexes and can interact with fibroblast growth
      factor (FGF) receptor 1. Overexpression of this receptor inhibits FGF induction
      of an FGF-responsive reporter gene in human 293T cells. This appears to occur as
      a result of specific inhibition of p42/p44 ERK in the absence of upstream MEK
      inhibition. This inhibitory effect is dependent upon a functional intracellular
      domain since deletion mutants missing the IL-17 receptor-like domain lack this
      inhibitory effect. These findings are consistent with the recent discovery of the
      zebrafish homologue, Sef (similar expression to fgf genes), which specifically
      antagonizes FGF signaling when ectopically expressed in zebrafish or Xenopus
      laevis embryos. Based on sequence and functional similarities, this novel IL-17
      receptor homologue represents a potential human SEF and is likely to play
      critical roles in endothelial or epithelial functions such as proliferation,
      migration, and angiogenesis.

PMID- 12807874
TI  - Characterization of mouse short-chain aldehyde reductase (SCALD), an enzyme
      regulated by sterol regulatory element-binding proteins.
AB  - Sterol regulatory element-binding proteins (SREBPs) enhance transcription of
      genes encoding all of the proteins required for the cellular synthesis and uptake
      of cholesterol and unsaturated fatty acids. Here, we use suppression subtractive
      hybridization to identify a previously unrecognized SREBP-enhanced gene in mice.
      The gene encodes a membrane-bound enzyme that we designate SCALD, for short-chain
      aldehyde reductase. We expressed SCALD in bacteria, purified it extensively, and
      studied its catalytic properties in detergent solution. The enzyme specifically
      uses NADPH to reduce a variety of short-chain aldehydes, including nonanal and 4
      hydroxy-2-nonenal. The enzyme also reduces retinaldehydes, showing equal activity
      for all-trans-retinal and 9-cis-retinal. Northern blot analysis indicates that
      SCALD is expressed most abundantly in mouse liver and testis. In the liver of
      mice, SCALD is suppressed by fasting and induced by refeeding, consistent with
      regulation by SREBPs. In testis, SCALD expression is restricted to pachytene
      spermatocytes, as revealed by visualization of mRNA and protein. SCALD is also
      expressed in four layers of the retina, including the outer segment of rods and
      cones, as revealed by immunohistochemistry. SCALD appears to be the mouse
      ortholog of the human protein that has been designated variously as prostate
      short-chain dehydrogenase/reductase 1, retinal reductase 1, and retinol
      dehydrogenase 11. In view of its ability to reduce short-chain aldehydes in
      addition to retinals, we propose that SCALD may be induced by SREBP in liver and
      other tissues to prevent toxicity from fatty aldehydes that are generated from
      oxidation of unsaturated fatty acids that are synthesized as a result of SREBP
      activity.

PMID- 12807875
TI  - Direct interaction of target SNAREs with the Kv2.1 channel. Modal regulation of
      channel activation and inactivation gating.
AB  - Previously we suggested that interaction between voltage-gated K+ channels and
      protein components of the exocytotic machinery regulated transmitter release.
      This study concerns the interaction between the Kv2.1 channel, the prevalent
      delayed rectifier K+ channel in neuroendocrine and endocrine cells, and syntaxin
      1A and SNAP-25. We recently showed in islet beta-cells that the Kv2.1 K+ current
      is modulated by syntaxin 1A and SNAP-25. Here we demonstrate, using co
      immunoprecipitation and immunocytochemistry analyses, the existence of a physical
      interaction in neuroendocrine cells between Kv2.1 and syntaxin 1A. Furthermore,
      using concomitant co-immunoprecipitation from plasma membranes and two-electrode
      voltage clamp analyses in Xenopus oocytes combined with in vitro binding
      analysis, we characterized the effects of these interactions on the Kv2.1 channel
      gating pertaining to the assembly/disassembly of the syntaxin 1A/SNAP-25 (target
      (t)-SNARE) complex. Syntaxin 1A alone binds strongly to Kv2.1 and shifts both
      activation and inactivation to hyperpolarized potentials. SNAP-25 alone binds
      weakly to Kv2.1 and probably has no effect by itself. Expression of SNAP-25
      together with syntaxin 1A results in the formation of t-SNARE complexes, with
      consequent elimination of the effects of syntaxin 1A alone on both activation and
      inactivation. Moreover, inactivation is shifted to the opposite direction, toward
      depolarized potentials, and its extent and rate are attenuated. Based on these
      results we suggest that exocytosis in neuroendocrine cells is tuned by the
      dynamic coupling of the Kv2.1 channel gating to the assembly status of the t
      SNARE complex.

PMID- 12807876
TI  - Hydroxylation-induced stabilization of the collagen triple helix. Further
      characterization of peptides with 4(R)-hydroxyproline in the Xaa position.
AB  - 4(R)-Hydroxyproline in the Yaa position of the -Gly-Xaa-Yaa-repeated sequence of
      collagen plays a crucial role in the stability of the triple helix. Since the
      peptide (4(R)-Hyp-Pro-Gly)10 does not form a triple helix, it was generally
      believed that polypeptides with a -Gly-4(R)-Hyp-Yaa-repeated sequence do not form
      a triple helix. Recently, we found that acetyl-(Gly-4(R)-Hyp-Thr)10-NH2 forms a
      triple helix in aqueous solutions. To further study the role of 4(R)
      hydroxyproline in the Xaa position, we made a series of acetyl-(Gly-4(R)-Hyp
      Yaa)10-NH2 peptides where Yaa was alanine, serine, valine, and allo-threonine. We
      previously hypothesized that the hydroxyl group of threonine might form a
      hydrogen bond to the hydroxyl group of 4(R)hydroxyproline. In water, only the
      threonine- and the valine-containing peptides were triple helical. The remaining
      peptides did not form a triple helix in water. In 1,2- and in 1,3-propanediol at
      4 degrees C, all the soluble peptides were triple helical. From the transition
      temperature of the triple helices, it was found that among the examined residues,
      threonine was the most stable residue in the acetyl-(Gly-4(R)-Hyp-Yaa)10-NH2
      peptide. The transition temperatures of the valine- and allo-threonine-containing
      peptides were 10 degrees lower than those of the threonine peptide. Surprisingly,
      the serine-containing peptide was the least stable. These results indicate that
      the stability of these peptides depends on the presence of a methyl group as well
      as the hydroxyl group and that the stereo configuration of the two groups is
      essential for the stability. In the threonine peptide, we hypothesize that the
      methyl group shields the interchain hydrogen bond between the glycine and the Xaa
      residue from water and that the hydroxyl groups of threonine and
      4(R)hydroxyproline can form direct or water-mediated hydrogen bonds.

PMID- 12807877
TI  - Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of
      complexin II.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by an expanded CAG repeat in the HD gene. We reported recently that
      complexin II, a protein involved in neurotransmitter release, is depleted from
      both the brains of mice carrying the HD mutation and from the striatum of post
      mortem HD brains. Here we show that this loss of complexin II is recapitulated in
      PC12 cells expressing the HD mutation and is accompanied by a dramatic decline in
      Ca2+-triggered exocytosis of neurotransmitter. Overexpression of complexin II
      (but not complexin I) rescued exocytosis, demonstrating that the decline in
      neurotransmitter release is a direct consequence of complexin II depletion.
      Complexin II depletion in the brain may account for some of the abnormalities in
      neurotransmission associated with HD.

PMID- 12807878
TI  - Visualization and mechanism of assembly of a glucocorticoid receptor.Hsp70
      complex that is primed for subsequent Hsp90-dependent opening of the steroid
      binding cleft.
AB  - A minimal system of five proteins, hsp90, hsp70, Hop, hsp40, and p23, assembles
      glucocorticoid receptor (GR).hsp90 heterocomplexes and causes the simultaneous
      opening of the steroid binding cleft to access by steroid. The first step in
      assembly is the ATP-dependent and hsp40 (YDJ-1)-dependent formation of a GR.hsp70
      complex that primes the receptor for subsequent ATP-dependent activation by
      hsp90, Hop, and p23. This study focuses on three aspects of the GR priming
      reaction with hsp70. First, we have visualized the primed GR.hsp70 complexes by
      atomic force microscopy, and we find the most common stoichiometry to be 1:1,
      with some complexes of a size approximately 1:2 and a few complexes of larger
      size. Second, in a recent study of progesterone receptor priming, it was shown
      that hsp40 binds first, leading to the notion that it targets hsp70 to the
      receptor. We show here that hsp40 does not perform such a targeting function in
      priming the GR. Third, we focus on a short amino-terminal segment of the ligand
      binding domain that is required for GR.hsp90 heterocomplex assembly. By using two
      glutathione S-transferase (GST)/ligand binding domain fusions with (GST/520C) and
      without (GST/554C) hsp90 binding and steroid binding activity, we show that the
      priming step with hsp70 occurs with GST/554C, and it is the subsequent assembly
      step with hsp90 that is defective.

PMID- 12807879
TI  - Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk)
      proteins.
AB  - Pseudomonas aeruginosa ExoT is a type III cytotoxin that functions as an anti
      internalization factor with an N-terminal RhoGAP domain and a C-terminal ADP
      ribosyltransferase domain. Although ExoT RhoGAP stimulates actin reorganization
      through the inactivation of Rho, Rac, and Cdc42, the function of the ADP
      ribosylation domain is unknown. The present study characterized the mammalian
      proteins that are ADP-ribosylated by ExoT, using two-dimensional SDS-PAGE and
      matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) analysis.
      ExoT ADP-ribosylated two cytosolic proteins in cell lysates upon type III
      delivery into cultured HeLa cells. MALDI-TOF mass spectrometry analysis
      identified the two proteins as Crk-I and Crk-II that are Src homology 2-3 domains
      containing adaptor proteins, which mediate signal pathways involving focal
      adhesion and phagocytosis. ExoT ADP-ribosylated recombinant Crk-I at a rate
      similar to the ADP-ribosylation of soybean trypsin inhibitor by ExoS. ExoS did
      not ADP-ribosylate Crk-I. ADP-ribosylation of Crk-I may be responsible for the
      anti-phagocytosis phenotype elicited by ExoT in mammalian cells.

PMID- 12807880
TI  - Stability of the Rel homology domain is critical for generation of NF-kappa B p50
      subunit.
AB  - The NF-kappa B transcription factor p50 and the Rel protein-specific
      transcription inhibitor p105 are both encoded by the nfkb1 gene. The p50 protein
      is incorporated within the N-terminal portion of p105 and is a unique product of
      proteasomal processing. Because proteasome-mediated proteolysis generally results
      in complete degradation of the substrate, how p50 survives the proteasomal
      processing remains unknown. Survival of proteasomal processing has also been
      observed recently for the yeast transcription factors SPT23 and MGA2, but the
      mechanism is also unclear. Here we show evidence that stability of the Rel
      homology domain (RHD) within the N-terminal portion of the NF-kappa B 1 protein
      is required for p50 generation. We demonstrated that proteolysis initiated at an
      internal location of the NF-kappa B 1 protein, which normally generates p50,
      degrades the N-terminal portion of the NF-kappa B 1 protein when the RHD is
      destabilized. Our findings highlight the critical role of the unique structure of
      the RHD for the survival of p50 during proteosomal processing.

PMID- 12807881
TI  - The Ret finger protein induces apoptosis via its RING finger-B box-coiled-coil
      motif.
AB  - The Ret finger protein (RFP) is a member of the tripartite motif family, which is
      characterized by a conserved RING finger, a B-box, and a coiled-coil domain
      (together called RBCC). Although RFP is known to become oncogenic when its RBCC
      moiety is connected to a tyrosine kinase domain by DNA rearrangement, its
      biological function is not well defined. Here we show that ectopic expression of
      RFP in human embryonic kidney 293 cells causes extensive apoptosis, as assessed
      by multiple criteria. RFP expression activates Jun N-terminal kinase and p38
      kinase and also increases caspase-3-like activity. However, RFP failed to release
      cytochrome c and, therefore, to increase caspase-9-like activity. RFP-induced
      apoptosis could be blocked by the caspase-8 inhibitor crmA and dominant negative
      ASK1 but not by Bcl-2. These results reveal a novel RFP death pathway that
      recruits mitogen-activated protein kinase and caspases independently of
      mitochondrial events. Domain mapping showed that the intact RBCC moiety is
      necessary for the pro-apoptotic function of RFP. Moreover, expression of the RBCC
      moiety further potentiated the pro-apoptotic activity and resulted in a 7-fold
      increase of caspase activation compared with that induced by full-length RFP.
      This suggests that a large number of tripartite motif family members sharing the
      RBCC moiety may participate in the control of cell survival.

PMID- 12807882
TI  - Energetic contribution of residues in the Runx1 Runt domain to DNA binding.
AB  - Core-binding factors (CBFs) are a small family of heterodimeric transcription
      factors that play critical roles in hematopoiesis and in the development of bone,
      stomach epithelium, and proprioceptive neurons. Mutations in CBF genes are found
      in leukemias, bone disorders, and gastric cancer. CBFs consist of a DNA-binding
      CBF alpha subunit and a non-DNA-binding CBF beta subunit. DNA binding and
      heterodimerization with CBF beta are mediated by the Runt domain in CBF alpha.
      Here we report an alanine-scanning mutagenesis study of the Runt domain that
      targeted amino acids identified by structural studies to reside at the DNA or CBF
      beta interface, as well as amino acids mutated in human disease. We determined
      the energy contributed by each of the DNA-contacting residues in the Runt domain
      to DNA binding both in the absence and presence of CBF beta. We propose
      mechanisms by which mutations in the Runt domain found in hematopoietic and bone
      disorders affect its affinity for DNA.

PMID- 12807883
TI  - Mutagenesis of the Runt domain defines two energetic hot spots for
      heterodimerization with the core binding factor beta subunit.
AB  - Core-binding factors (CBFs) are a small family of heterodimeric transcription
      factors that play critical roles in several developmental pathways and in human
      disease. Mutations in CBF genes are found in leukemias, bone disorders, and
      gastric cancers. CBFs consist of a DNA-binding CBF alpha subunit (Runx1, Runx2,
      or Runx3) and a non-DNA-binding CBF beta subunit. CBF alpha binds DNA in a
      sequence-specific manner, whereas CBF beta enhances DNA binding by CBF alpha.
      Both DNA binding and heterodimerization with CBF beta are mediated by a single
      domain in the CBF alpha subunits known as the "Runt domain." We analyzed the
      energetic contribution of amino acids in the Runx1 Runt domain to
      heterodimerization with CBF beta. We identified two energetic "hot spots" that
      were also found in a similar analysis of CBF beta (Tang, Y.-Y., Shi, J., Zhang,
      L., Davis, A., Bravo, J., Warren, A. J., Speck, N. A., and Bushweller, J. H.
      (2000) J. Biol. Chem. 275, 39579-39588). The importance of the hot spot residues
      for Runx1 function was demonstrated in in vivo transient transfection assays.
      These data refine the structural analyses and further our understanding of the
      Runx1-CBF beta interface.

PMID- 12807884
TI  - D1 ring is stable and nucleotide-independent, whereas D2 ring undergoes major
      conformational changes during the ATPase cycle of p97-VCP.
AB  - The 97-kDa valosin-containing protein (p97-VCP) belongs to the AAA (ATPases
      associated with various cellular activities) family and acts as a molecular
      chaperone in diverse cellular events, including ubiquitinproteasome-mediated
      degradation. We previously showed that VCP contains a substrate-binding domain,
      N, and two conserved ATPase domains, D1 and D2, of which D2 is responsible for
      the major enzyme activity. VCP has a barrel-like structure containing two stacked
      homo-hexameric rings made of the D1 and D2 domains, and this structure is
      essential for its biological functions. During ATPase cycles, VCP undergoes
      conformational changes that presumably apply tensions to the bound substrate,
      leading to the disassembly of protein complexes or unfolding of the substrate.
      How ATPase activity is coupled with the conformational changes in VCP complex and
      the D1 and D2 rings is not clear. In this report, we took biochemical approaches
      to study the structure of VCP in different nucleotide conditions to depict the
      conformational changes in the ATPase cycles. In contrast to many AAA chaperones
      that require ATP/ADP to form oligomers, both wild type VCP and ATP-binding site
      mutants can form hexamers without the addition of nucleotide. This nucleotide
      independent hexamerization requires an intact D1 and the down-stream linker
      sequence of VCP. Tryptophan fluorescence and trypsin digestion analyses showed
      that ATP/ADP binding induces dramatic conformational changes in VCP. These
      changes do not require the presence of an intact ATP-binding site in D1 and is
      thus mainly attributed to the D2 domain. We propose a model whereby D1, although
      undergoing minor conformational changes, remains as a relatively trypsin
      resistant hexameric ring throughout the ATPase cycle, whereas D2 only does so
      when it binds to ATP or ADP. After ADP is released at the end of the ATP
      hydrolysis, D2 ring is destabilized and adopts a relatively flexible and open
      structure.

PMID- 12807885
TI  - PGC-1beta in the regulation of hepatic glucose and energy metabolism.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)
      is a transcriptional coactivator that regulates multiple aspects of cellular
      energy metabolism, including mitochondrial biogenesis, hepatic gluconeogenesis,
      and beta-oxidation of fatty acids. PGC-1alpha mRNA levels are increased in both
      type-1 and type-2 diabetes and may contribute to elevated hepatic glucose
      production in diabetic states. We have recently described PGC-1beta, a novel
      transcriptional coactivator that is a homolog of PGC-1alpha. Although PGC-1beta
      shares significant sequence similarity and tissue distribution with PGC-1alpha,
      the biological activities of PGC-1beta in the regulation of cellular metabolism
      is unknown. In this study, we used an adenoviral-mediated expression system to
      study the function of PGC-1beta both in cultured hepatocytes and in the liver of
      rats. PGC-1beta, like PGC-1alpha, potently induces the expression of an array of
      mitochondrial genes involved in oxidative metabolism. However, in contrast to PGC
      1alpha, PGC-1beta poorly activates the expression of gluconeogenic genes in
      hepatocytes or liver in vivo, illustrating that these two coactivators play
      distinct roles in hepatic glucose metabolism. The reduced ability of PGC-1beta to
      induce gluconeogenic genes is due, at least in part, to its inability to
      physically associate with and coactivate hepatic nuclear receptor 4alpha
      (HNF4alpha) and forkhead transcription factor O1 (FOXO1), two critical
      transcription factors that mediate the activation of gluconeogenic gene
      expression by PGC-1alpha. These data illustrate that PGC-1beta and PGC-1alpha
      have distinct arrays of activities in hepatic energy metabolism.

PMID- 12807886
TI  - Biosynthesis of phytosterols. Kinetic mechanism for the enzymatic C-methylation
      of sterols.
AB  - Cloned soybean sterol methyltransferase was purified from Escherichia coli to gel
      electrophoretic homogeneity. From initial velocity experiments, catalytic
      constants for substrates best suited for the first and second C1 transfer
      activities, cycloartenol and 24(28)-methylenelophenol, were 0.01 and 0.001 s-1,
      respectively. Two-substrate kinetic analysis using cycloartenol and S-adenosyl-l
      methionine (AdoMet) generated an intersecting line pattern characteristic of a
      ternary complex kinetic mechanism. The high energy intermediate analog 25
      azacycloartanol was a noncompetitive inhibitor versus cycloartenol and an
      uncompetitive inhibitor versus AdoMet. The dead end inhibitor analog
      cyclolaudenol was competitive versus cycloartenol and uncompetitive versus
      AdoMet. 24(28)-Methylenecycloartanol and AdoHcy generated competitive and
      noncompetitive kinetic patterns, respectively, with respect to AdoMet. Therefore,
      24(28)-methylenecycloartanol combines with the same enzyme form as does
      cycloartenol and must be released from the enzyme before AdoHcy. 25
      Azacycloartanol inhibited the first and second C1 transfer activities with about
      equal efficacy (Ki = 45 nm), suggesting that the successive C-methylation of the
      Delta 24 bond occurs at the same active center. Comparison of the initial
      velocity data using AdoMet versus [2H3-methyl]AdoMet as substrates tested against
      saturating amounts of cycloartenol indicated an isotope effect on VCH3/VCD3 close
      to unity. [25-2H]24(28)-Methylenecycloartanol, [28E-2H]24 (28)
      methylenelanosterol, and [28Z-2H]24(28)-methylene lanosterol were prepared and
      paired with AdoMet or [methyl-3H3]AdoMet to examine the kinetic isotope effects
      attending the C-28 deprotonation in the enzymatic synthesis of 24-ethyl(idene)
      sterols. The stereochemical features as well as the observation of isotopically
      sensitive branching during the second C-methylation suggests that the two
      methylation steps can proceed by a change in chemical mechanism resulting from
      differences in sterol structure, concerted versus carbocation; the kinetic
      mechanism remains the same during the consecutive methylation of the Delta 24
      bond.

PMID- 12807887
TI  - Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5
      beta 1 and alpha v beta 3 integrins.
AB  - Fibrillins are the major glycoprotein components of microfibrils that form a
      template for tropoelastin during elastic fibrillogenesis. We have examined cell
      adhesion to assembled purified microfibrils, and its molecular basis. Human
      dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to
      microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha
      5 beta 1 interactions with fibrillin ligands were identified, but integrin alpha
      v beta 3 also contributed to cell adhesion. Fluorescence-activated cell sorting
      analysis confirmed the presence of abundant alpha 5 beta 1 and some alpha v beta
      3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp
      containing fibrillin-1 protein fragments induced signaling events that led to
      cell spreading, altered cytoskeletal organization, and enhanced extracellular
      fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or
      fibronectin implied substrate-specific alpha 5 beta 1-mediated cellular
      responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified
      within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin
      ligands was enhanced by antibody-induced beta1 integrin activation. A375-SM
      melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly
      through alpha v beta 3, whereas HT1080 cells used mainly alpha 5 beta 1. This
      study has shown that fibrillin microfibrils mediate cell adhesion, that alpha 5
      beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1
      receptors, and that cellular interactions with fibrillin-1 influence cell
      behavior.

PMID- 12807888
TI  - Bi-directional regulation of brown fat adipogenesis by the insulin receptor.
AB  - Insulin is a potent inducer of adipogenesis, and differentiation of adipocytes
      requires many components of the insulin signaling pathway, including the insulin
      receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K). Brown pre
      adipocytes in culture exhibit low levels of insulin receptor (IR), and during
      differentiation there is both an increase in total IR levels and a shift in the
      alternatively spliced forms of IR from the A isoform (-exon 11) to the B isoform
      (+exon 11). Brown pre-adipocyte cell lines from insulin receptor-deficient mice
      exhibit dramatically impaired differentiation and an inability to regulate
      alternative splicing of the insulin receptor. Surprisingly, re-expression of
      either splice isoform of IR in the IR-deficient cells fails to rescue
      differentiation in these cells. Likewise, overexpression of IR in control IRlox
      cells also results in inhibition of differentiation and a failure to accumulate
      expression of the adipogenic markers peroxisome proliferator-activated receptor
      gamma, Glut4, and fatty acid synthase, although cells overexpressing IR retain
      the ability to activate PI3K and down-regulate mitogen-activated protein kinase
      (MAPK) phosphorylation. Thus, differentiation of brown adipocytes requires a
      timed and regulated expression of IR, and either the absence or overabundance of
      insulin receptors in these cells dramatically inhibits differentiation.

PMID- 12807889
TI  - Targeting a surface cavity of alpha 1-antitrypsin to prevent conformational
      disease.
AB  - Conformational diseases are caused by a structural rearrangement within a protein
      that results in aberrant intermolecular linkage and tissue deposition. This is
      typified by the polymers that form with the Z deficiency variant of alpha 1
      antitrypsin (Glu-342 --> Lys). These polymers are retained within hepatocytes to
      form inclusions that are associated with hepatitis, cirrhosis, and hepatocellular
      carcinoma. We have assessed a surface hydrophobic cavity in alpha1-antitrypsin as
      a potential target for rational drug design in order to prevent polymer formation
      and the associated liver disease. The introduction of either Thr-114 --> Phe or
      Gly-117 --> Phe on strand 2 of beta-sheet A within this cavity significantly
      raised the melting temperature and retarded polymer formation. Conversely, Leu
      100 --> Phe on helix D accelerated polymer formation, but this effect was
      abrogated by the addition of Thr-114 --> Phe. None of these mutations affected
      the inhibitory activity of alpha 1-antitrypsin. The importance of these
      observations was underscored by the finding that the Thr-114 --> Phe mutation
      reduced polymer formation and increased the secretion of Z alpha 1-antitrypsin
      from a Xenopus oocyte expression system. Moreover cysteine mutants within the
      hydrophobic pocket were able to bind a range of fluorophores illustrating the
      accessibility of the cavity to external agents. These results demonstrate the
      importance of this cavity as a site for drug design to ameliorate polymerization
      and prevent the associated conformational disease.

PMID- 12807890
TI  - The mitochondrial ornithine transporter. Bacterial expression, reconstitution,
      functional characterization, and tissue distribution of two human isoforms.
AB  - Two isoforms of the human ornithine carrier, ORC1 and ORC2, have been identified
      by overexpression of the proteins in bacteria and by study of the transport
      properties of the purified proteins reconstituted into liposomes. Both transport
      L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by
      unidirectional mechanisms, and they are inactivated by the same inhibitors. ORC2
      has a broader specificity than ORC1, and L- and D-histidine, L-homoarginine, and
      D-isomers of ornithine, lysine, and ornithine are all substrates. Both proteins
      are expressed in a wide range of human tissues, but ORC1 is the predominant form.
      The highest levels of expression of both isoforms are in the liver. Five mutant
      forms of ORC1 associated with the human disease hyperornithinemia-hyperammonemia
      homocitrullinuria were also made. The mutations abolish the transport properties
      of the protein. In patients with hyperornithinemia-hyperammonemia
      homocitrullinuria, isoform ORC2 is unmodified, and its presence compensates
      partially for defective ORC1.

PMID- 12807891
TI  - Hormonal control of ADP-ribosyl cyclase activity in pancreatic acinar cells from
      rats.
AB  - Cyclic ADP-ribose, a metabolite of NAD+ evokes Ca2+ release from intracellular
      stores in different cells. We have determined the activity of cADPr-producing
      enzymes (ADP-ribosyl cyclases) in different cellular fractions prepared from
      isolated pancreatic acinar cells by measuring the conversion of the beta-NAD+
      analogs 1,N6-etheno-NAD and nicotinamide guanine dinucleotide to the fluorescent
      products 1,N6-etheno-cADPr and cyclic GDP-ribose, respectively. Substrate/product
      analyses were carried out by reverse-phase high pressure liquid chromatography.
      In all subcellular fractions examined (cytosol, mitochondria, plasma, and
      intracellular membranes), ADP-ribosyl cyclase activity was detected except in
      zymogen granular membranes. Western blot analysis and immunoprecipitation
      experiments revealed the presence of the ADP-ribosyl cyclase CD38 in both plasma
      membranes and mitochondria but not in the cytosol. Hormonal stimulation of intact
      acinar cells for 1 min with acetylcholine (ACh), cholecystokinin (CCK), or a
      membrane-permeant analog of cGMP increased ADP-ribosyl cyclase activity in the
      cytosol by 1.8-, 1.6-, and 1.9-fold, respectively, as compared with the control
      but had no effect in any other fraction. Both ACh and CCK also increased
      accumulation of cGMP in the cells by about 2-fold. Bombesin had no significant
      effect on either ADP-ribosyl cyclase activity or cGMP accumulation within this
      short period of stimulation. We conclude that at least two types of ADP-ribosyl
      cyclases are present in pancreatic acinar cells: membrane-bound CD38 and a
      cytosolic enzyme different from CD38. Stimulation of pancreatic acinar cells with
      CCK or ACh results in exclusive activation of the cytosolic ADP-ribosyl cyclase
      activity, most likely mediated by cGMP.

PMID- 12807892
TI  - Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via
      interaction with phospholipids and the apolipoprotein E receptor 2'.
AB  - Patients with prolonged clotting times caused by lupus anticoagulant (LAC) are at
      risk for thrombosis. This paradoxal association is not understood. LAC is
      frequently caused by anti-beta2-glycoprotein I (beta 2GPI) antibodies. Antibody
      induced dimerization of beta 2GPI increases the affinity of beta 2GPI for
      phospholipids, explaining the observed prolonged clotting times. We constructed
      dimers of beta 2GPI that mimic effects of beta 2GPI-anti-beta 2GPI antibody
      complexes, and we studied their effects on platelet adhesion and thrombus
      formation in a flow system. Dimeric beta 2GPI increased platelet adhesion to
      collagen by 150% and increased the number of large aggregates. We also observed
      increased platelet adhesion to collagen when whole blood was spiked with patient
      derived polyclonal anti-beta 2GPI or some, but not all, monoclonal anti-beta 2GPI
      antibodies with LAC activity. These effects could be abrogated by inhibition of
      thromboxane synthesis. A LAC-positive monoclonal anti-beta 2GPI antibody, which
      did not affect platelet adhesion, prevented the induced increase in platelet
      adhesion by beta 2GPI dimers. Furthermore, increased platelet adhesion
      disappeared after preincubation with receptor-associated protein, a universal
      inhibitor of interaction of ligands with members of the low density lipoprotein
      receptor family. Using co-immunoprecipitation, it was shown that dimeric beta
      2GPI can interact with apolipoprotein E receptor 2 (apoER2'), a member of the low
      density lipoprotein receptor family present on platelets. These results
      demonstrate that dimeric beta 2GPI induces increased platelet adhesion and
      thrombus formation, which depends on activation via apoER2'.

PMID- 12807893
TI  - Selected contribution: Bone adaptation with aging and long-term caloric
      restriction in Fischer 344 x Brown-Norway F1-hybrid rats.
AB  - Rodents are commonly used as models for human aging because of their relatively
      short life span, the ease of obtaining age-specific tissue samples, and lower
      cost. However, age-associated disease may confound inbred animal studies. For
      example, numerous physiologically significant lesions, such as chronic
      nephropathy, are more common in aged Fischer 344 (F344) rats than in other
      strains (Bronson RT, Genetic Effects of Aging, 1990). Conversely, F344 x Brown
      Norway F1-hybrid (F344BN) rats, developed by the National Institute on Aging for
      aging research, live considerably longer and have fewer pathologies at any given
      age vs. inbred strains (Lipman RD, Chrisp CE, Hazzard DG, and Bronson RT, J
      Gerontol A Biol Sci Med Sci 51: 54-59, 1996). To our knowledge, there are no data
      regarding the effect of age on bone geometry and mechanics in this strain of rat.
      Furthermore, caloric restriction (CR) extends the mean and maximal life span of
      animals and significantly reduces age-associated disease but may have adverse
      consequences for bone growth and mechanics. Thus we investigated the effects of
      age and CR on bone geometry and mechanics in the axial and appendicular skeleton
      of F344 Brown-Norway rats. Ad libitum fed rats were assessed at 8 mo (young
      adult; n = 6), 28 mo (late middle age; n = 5), and 36 mo (senescence; n = 6). CR
      rats were assessed at 28 mo (n = 6). Tibiae and the sixth lumbar vertebrae (L6)
      were dissected, scanned (micro-computed tomography) to determine geometry, and
      tested mechanically. From 8 to 36 mo, there were no significant changes in L6
      geometry, and only the cross-sectional moment of inertia changed (increased) with
      the tibia. CR-induced body mass reductions accounted for changes in L6 load at
      proportional limit, maximal load, and stiffness (structural properties), but
      altered tibial structural properties were independent of body mass. In tibiae,
      geometric changes dominated alterations in structural properties. Those data
      demonstrated that, whereas aging in ad libitum-fed animals induced minor changes
      in bone mechanics, axial and appendicular bones were adversely influenced by CR
      in late-middle-aged animals in different manners.

PMID- 12807894
TI  - High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model
      of ventilator-induced lung injury.
AB  - Mechanical ventilation has been demonstrated to exacerbate lung injury, and a
      sufficiently high tidal volume can induce injury in otherwise healthy lungs.
      However, it remains controversial whether injurious ventilation per se, without
      preceding lung injury, can initiate cytokine-mediated pulmonary inflammation. To
      address this, we developed an in vivo mouse model of acute lung injury produced
      by high tidal volume (Vt) ventilation. Anesthetized C57BL6 mice were ventilated
      at high Vt (34.5 +/- 2.9 ml/kg, mean +/- SD) for a duration of 156 +/- 17 min
      until mean blood pressure fell below 45 mmHg (series 1); high Vt for 120 min
      (series 2); or low Vt (8.8 +/- 0.5 ml/kg) for 120 or 180 min (series 3). High Vt
      produced progressive lung injury with a decrease in respiratory system
      compliance, increase in protein concentration in lung lavage fluid, and lung
      pathology showing hyaline membrane formation. High-Vt ventilation was associated
      with increased TNF-alpha in lung lavage fluid at the early stage of injury
      (series 2) but not the later stage (series 1). In contrast, lavage fluid
      macrophage inflammatory protein-2 (MIP-2) was increased in all high-Vt animals.
      Lavage fluid from high-Vt animals contained bioactive TNF-alpha by WEHI bioassay.
      Low-Vt ventilation induced minimal changes in physiology and pathology with
      negligible TNF-alpha and MIP-2 proteins and TNF-alpha bioactivity. These results
      demonstrate that high-Vt ventilation in the absence of underlying injury induces
      intrapulmonary TNF-alpha and MIP-2 expression in mice. The apparently transient
      nature of TNF-alpha upregulation may help explain previous controversy regarding
      the involvement of cytokines in ventilator-induced lung injury.

PMID- 12807895
TI  - Physical and pubertal development in young male gymnasts.
AB  - The purpose of this study was to evaluate the effect of intense training on
      physical growth and sexual maturation in young male gymnasts. Physical
      development, pubertal development, testosterone levels, energy expenditure, and
      relative body fat were examined in 21 circumpubertal male gymnasts (13.3 +/- 0.3
      yr) and 24 age-matched controls (13.5 +/- 0.3 yr). Subjects completed a self
      assessment of genital and pubic hair development with the use of the Tanner
      scale. All subjects were measured for height, weight, and salivary testosterone
      levels (T). The Physical Activity Questionnaire for Adolescents was used to
      estimate weekly energy expenditure in metabolic equivalents. Percent body fat
      (%BF) was assessed by using bioelectrical impedance analysis. Developmental
      stages and T, as well as height and weight, were not different between groups.
      Energy expenditure was significantly higher (P <or= 0.05) and %BF was lower (P
      <or= 0.05) in athletes than in controls, but lean body mass was not significantly
      different between groups. Energy expenditure was negatively correlated (P <or=
      0.05) with %BF but not related to T. Developmental stages were strongly (P <or=
      0.05) related to T but not to energy expenditure or %BF. It is concluded that,
      although there is a higher energy expenditure accompanying intense training in
      young male athletes, their body composition is not necessarily affected, and
      there is no determined effect on their physical and pubertal development.

PMID- 12807896
TI  - Corticosteroids and skeletal muscle function in cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) have reduced peripheral muscle strength. We
      tested the hypothesis that steroid treatment contributes to muscle weakness in
      adults with CF. Twenty-three stable CF patients were studied. Measurements
      included knee extensor (KE), knee flexor (KF), elbow flexor (EF), handgrip (HG),
      expiratory (Pemax), and inspiratory (Pimax) muscle strengths. Spirometry, body
      mass index (BMI), and days spent in hospital over the preceding 12 mo (DH) were
      also measured. Average daily dose of prednisolone over the preceding 12 mo (ADD)
      was 5.1 mg/day. Pearson's correlation analysis revealed that ADD correlated
      significantly with skeletal muscle strengths (KF%, r = -0.63, P < 0.01) with the
      exception of HG%. These findings are independent of age, BMI, pulmonary function,
      and DH. Multiple-regression analysis revealed that ADD was the most significant
      predictor of all measures of skeletal muscle function except HG%. It was
      independently responsible for 54% of the variance in Pimax%, for 46% of the
      variance in Pemax%, for 45% of the variance in KE%, for 39% of the variance in
      KF%, and for 41% of the variance in EF%. Concomitant medications (e.g.,
      theophylline) were shown to have no causative effect. Corticosteroids contribute
      to the skeletal muscle weakness seen in CF patients. The correlation of proximal
      muscle strength, but not HG strength, with steroid dosage further supports a
      cause-effect relationship.

PMID- 12807897
TI  - C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in
      men and women.
AB  - We performed gene screening of the ciliary neurotrophic factor receptor (CNTFR)
      gene and genotyped three newly identified polymorphisms: C-1703T in the 5'
      promoter region, T1069A in intron 5, and C174T in exon 9. We studied the
      association of these CNTFR variants with muscle strength, mass, and body
      composition in 465 men and women (20-90 yr) from the Baltimore Longitudinal Study
      of Aging. Only the C174T variant was significantly associated with muscle-related
      phenotypes. In the entire cohort, when corrected for age, sex, race, physical
      activity, and height, homozygotes for the common C allele at C174T (CC) exhibited
      lower total body mass and body mass index than carriers of the rare T allele,
      which appeared to be due to significant differences in total nonosseous fat-free
      mass (FFM) (48.0 +/- 0.4 vs. 50.0 +/- 0.7 kg; P = 0.011) and lower limb FFM (16.5
      +/- 0.1 vs. 17.2 +/- 0.2 kg; P = 0.002). The CC group also exhibited
      significantly lower quadriceps concentric and eccentric isokinetic strength
      values at both 30 and 180 degrees /s than the T allele carriers (all P < 0.04),
      but these differences were no longer significant after adjustment for lower limb
      FFM. There were no significant sex-by-genotype interactions. The results indicate
      that the C174T polymorphism in exon 9 of CNTFR is significantly associated with
      FFM in men and women, with concomitant differences in muscular strength.

PMID- 12807898
TI  - Accuracy of noninvasive estimates of respiratory muscle effort during spontaneous
      breathing in restrictive diseases.
AB  - Mean inspiratory pressure (Pi), estimated from the occlusion pressure at the
      mouth and the inspiratory time, is useful as a noninvasive estimate of
      respiratory muscle effort during spontaneous breathing in normal subjects and
      patients with chronic obstructive pulmonary disease. The aim of this study was to
      compare the Pi with respect to mean esophageal pressure (Pes) in patients with
      restrictive disorders. Eleven healthy volunteers, 12 patients with chest wall
      disease, 14 patients with usual interstitial pneumonia, and 17 patients with
      neuromuscular diseases were studied. Pi, Pes, and mean transdiaphragmatic
      pressure were simultaneously measured. Tension-time indexes of diaphragm (TTdi)
      and inspiratory muscles (TTmu) were also determined. In neuromuscular patients,
      significant correlations were found between Pi and Pes, Pi and transdiaphragmatic
      pressure, and TTmu and TTdi. A moderate agreement between Pi and Pes and between
      TTmu and TTdi was found. No significant correlation between these parameters was
      found in the other patient groups. These findings suggest that Pi is a good
      surrogate for the invasive measurement of respiratory muscle effort during
      spontaneous breathing in neuromuscular patients.

PMID- 12807899
TI  - Gender differences in the regulation of amino acid metabolism.
AB  - Exercising men, compared with women, have a greater increase in leucine oxidation
      but not lysine rate of appearance. The cause for this sexual dimorphism is
      unknown; however, an inhibition of beta-adrenoreceptor activity has previously
      been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan
      SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and
      Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison
      of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta1,beta2
      blockade) and a placebo control by using a double-blind crossover protocol.
      Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h)
      after 7 days of dietary control. During exercise with beta-blockade, men had an
      increased nonprotein respiratory exchange ratio (P < 0.001), whereas women had an
      increased circulation of free fatty acids (P < 0.001). The genders also displayed
      distinct differences in exercise amino acid kinetics. The men, but not the women,
      increased leucine oxidation (P < 0.005) and lysine rate of appearance (P < 0.009)
      when exercising during beta-adrenergic blockade. This study indicates that during
      beta-blockade, exercising men increase their need for amino acids (and
      carbohydrate) to fuel energy needs, whereas women increase their mobilization of
      fat, thereby requiring less alternative fuels such as carbohydrate and amino
      acids. Gender-specific fuel preferences during exercise are regulated by beta
      adrenergic-receptor activity. Substrate availability during exercise appears to
      modulate the amino acid oxidation differences between genders.

PMID- 12807900
TI  - Impaired muscle Ca2+ and K+ regulation contribute to poor exercise performance
      post-lung transplantation.
AB  - Lung transplant recipients (LTx) exhibit marked peripheral limitations to
      exercise. We investigated whether skeletal muscle Ca2+ and K+ regulation might be
      abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and
      arterialized venous plasma [K+] (where brackets denote concentration) were
      measured during incremental exercise. Vastus lateralis muscle was biopsied at
      rest and analyzed for sarcoplasmic reticulum Ca2+ release, Ca2+ uptake, and Ca2+
      ATPase activity rates; fiber composition; Na+-K+-ATPase (K+-stimulated 3-O
      methylfluorescein phosphatase) activity and content ([3H]ouabain binding sites);
      as well as for [H+] and H+-buffering capacity. Peak oxygen consumption was 47%
      less in LTx (P < 0.05). LTx had lower Ca2+ release (34%), Ca2+ uptake (31%), and
      Ca2+-ATPase activity (25%) than controls (P < 0.05), despite their higher type II
      fiber proportion (LTx, 75.0 +/- 5.8%; controls, 43.5 +/- 2.1%). Muscle [H+] was
      elevated in LTx (P < 0.01), but buffering capacity was similar to controls.
      Muscle 3-O-methylfluorescein phosphatase activity was 31% higher in LTx (P <
      0.05), but [3H]ouabain binding content did not differ significantly. However,
      during exercise, the rise in plasma [K+]-to-work ratio was 2.6-fold greater in
      LTx (P < 0.05), indicating impaired K+ regulation. Thus grossly subnormal muscle
      calcium regulation, with impaired potassium regulation, may contribute to poor
      muscular performance in LTx.

PMID- 12807901
TI  - Fidelity of primate cell repair of a double-strand break within a (CTG).(CAG)
      tract. Effect of slipped DNA structures.
AB  - At least 15 human diseases are caused by the instability of gene-specific
      (CTG).(CAG) repeats. The precise mechanism of instability remains unknown, though
      bacterial and yeast models have suggested a role for aberrant repair of double
      strand breaks (DSBs). Using an established primate DSB repair system, we have
      investigated the fidelity of repair of a DSB within a (CTG).(CAG) repeat tract.
      DSB repair substrates were generated from plasmids that are stably replicated in
      their circular form, permitting us to highlight the effects of DSB repair on
      repeat stability and minimize the contribution of replication. DSBs were
      introduced into repeat-containing plasmids using a unique BsmI site, such that
      the entire repeat tract comprised one free end of the linearized plasmid.
      Substrates containing 17, 47, and 79 repeats, in either their linear duplex form
      or containing slipped structures (out-of-register interstrand mispairings at
      repeat sequences), were transiently transfected into primate cells. Linearized
      plasmids with repeats were repaired with mildly reduced efficiency, while the
      presence of slipped structures considerably reduced repair efficiency. The
      repaired products were characterized for alterations within the repeat tract and
      flanking sequence. DSB repair induced predominantly repeat deletions. Notably, a
      polarized/directional deletion effect was observed, in that the repetitive end of
      the DSB was preferentially removed. This phenomenon was dramatically enhanced
      when slipped structures were present within the repeat tract, providing the first
      evidence for error-prone processing of slipped-strand structures. These results
      suggest the existence of primate nuclease activities that are specific for
      (CTG).(CAG) repeats and the structures they form.

PMID- 12807902
TI  - Photoaffinity labeling demonstrates physical contact between vasoactive
      intestinal peptide and the N-terminal ectodomain of the human VPAC1 receptor.
AB  - Vasoactive intestinal peptide (VIP) is a prominent neuropeptide whose actions are
      mediated by VPAC receptors belonging to class II G protein-coupled receptors. To
      identify contact sites between VIP and its VPAC1 receptor, an analog of VIP
      substituted with a photoreactive para-benzoyl-l-Phe (Bpa) at position 22 has been
      synthesized and evaluated in Chinese hamster ovary cells stably expressing the
      recombinant human receptor. Bpa22-VIP and native VIP are equipotent in
      stimulating adenylyl cyclase activity in cell membranes. Cyanogen bromide
      cleavage of the covalent 125I-[Bpa22-VIP]-hVPAC1R complex yielded a single
      labeled fragment of 30 kDa that shifted to 11 after deglycosylation, most
      consistent with the 67-137 fragment of the receptor N-terminal ectodomain.
      Further cleavage of this fragment with V8 endoproteinase and creation of receptor
      mutants with new CNBr cleavage sites (XaMet), demonstrated that 125I-[Bpa22-VIP]
      was covalently attached to the short receptor 109-120 fragment (GWTHLEPGPYPI). In
      a three-dimensional model of the receptor N-terminal ectodomain, this fragment is
      located on one edge of the putative VIP binding groove and encompasses several
      amino acids previously shown to be crucial for VIP binding (reviewed in Laburthe,
      M., Couvineau, A., and Marie, J. C. (2002) Receptors Channels 8, 137-153). Our
      data provide the first direct evidence for a physical contact between VIP and the
      N-terminal ectodomain of the hVPAC1 receptor.

PMID- 12807903
TI  - WW domain-containing protein YAP associates with ErbB-4 and acts as a co
      transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that
      translocates to the nucleus.
AB  - The ErbB-4 receptor protein-tyrosine kinase is proteolytically processed by
      membrane proteases in response to the ligand or 12-O-tetradecanoylphorbol-13
      acetate stimulation resulting in the cytoplasmic fragment translocating to the
      cell nucleus. The WW domain-containing co-transcriptional activator Yes
      associated protein (YAP) associates physically with the full-length ErbB-4
      receptor and functionally with the ErbB-4 cytoplasmic fragment in the nucleus.
      The YAP.ErbB4 complex is mediated by the first WW domain of YAP and the most
      carboxyl-terminal PPXY motif of ErbB-4. In human tissues, we documented the
      expression of YAP1 with a single WW domain and YAP2 with two WW domains. It is
      known that the COOH-terminal fragment of ErbB4 does not have transcriptional
      activity by itself; however, we show here that in the presence of YAP its
      transcriptional activity is revealed. There is a difference in the extent of
      transactivation activity among YAP isoforms: YAP2 is the stronger activator
      compared with YAP1. This transactivation is abolished by mutations that abrogate
      the YAP.ErbB4 complex formation. The unphosphorylatable mutation that increases
      the nuclear localization of YAP increases transcription activity. The COOH
      terminal fragment of ErbB-4 and full-length YAP2 overexpressed in cells partially
      co-localize to the nucleus. Our data indicate that YAP is a potential signaling
      partner of the full-length ErbB4 receptor at the membrane and of the COOH
      terminal fragment of ErbB-4 that translocates to the nucleus to regulate
      transcription.

PMID- 12807904
TI  - Cell cycle-associated changes in Slingshot phosphatase activity and roles in
      cytokinesis in animal cells.
AB  - During cytokinesis the actomyosin-based contractile ring is formed at the
      equator, constricted, and then disassembled prior to cell abscission. Cofilin
      stimulates actin filament disassembly and is implicated in the regulation of
      contractile ring dynamics. However, little is known about the mechanism
      controlling cofilin activity during cytokinesis. Cofilin is inactivated by
      phosphorylation on Ser-3 by LIM-kinase-1 (LIMK1) and is reactivated by a protein
      phosphatase Slingshot-1 (SSH1). Here we show that the phosphatase activity of
      SSH1 decreases in the early stages of mitosis and is elevated in telophase and
      cytokinesis in HeLa cells, a time course correlating with that of cofilin
      dephosphorylation. SSH1 co-localizes with F-actin and accumulates onto the
      cleavage furrow and the midbody. Expression of a phosphatase-inactive SSH1
      induces aberrant accumulation of F-actin and phospho-cofilin near the midbody in
      the final stage of cytokinesis and frequently leads to the regression of the
      cleavage furrow and the formation of multinucleate cells. Co-expression of
      cofilin rescued the inhibitory effect of phosphatase-inactive SSH1 on
      cytokinesis. These results suggest that SSH1 plays a critical role in cytokinesis
      by dephosphorylating and reactivating cofilin in later stages of mitosis.

PMID- 12807905
TI  - Nanoparticles of compacted DNA transfect postmitotic cells.
AB  - Charge-neutral DNA nanoparticles have been developed in which single molecules of
      DNA are compacted to their minimal possible size. We speculated that the small
      size of these DNA nanoparticles may facilitate gene transfer in postmitotic
      cells, permitting nuclear uptake across the 25-nm nuclear membrane pore. To
      determine whether DNA nanoparticles can transfect nondividing cells, growth
      arrested neuroblastoma and hepatoma cells were transfected with DNA/liposome
      mixtures encoding luciferase. In both models, growth-arrested cells were robustly
      transfected by compacted DNA (6,900-360-fold more than naked DNA). To evaluate
      mechanisms responsible for enhanced transfection, HuH-7 cells were microinjected
      with naked or compacted plasmids encoding enhanced green fluorescent protein.
      Cytoplasmic microinjection of DNA nanoparticles generated a approximately 10-fold
      improvement in transgene expression as compared with naked DNA; this enhancement
      was reversed by the nuclear pore inhibitor, wheat germ agglutinin. To determine
      the upper size limit for gene transfer, DNA nanoparticles of various sizes were
      microinjected into the cytoplasm. A marked decrease in transgene expression was
      observed as the minor ellipsoidal diameter approached 25 nm. In summary, suitably
      sized DNA nanoparticles productively transfect growth arrested cells by
      traversing the nuclear membrane pore.

PMID- 12807907
TI  - Essential cell division protein FtsZ assembles into one monomer-thick ribbons
      under conditions resembling the crowded intracellular environment.
AB  - Experimental conditions that simulate the crowded bacterial cytoplasmic
      environment have been used to study the assembly of the essential cell division
      protein FtsZ from Escherichia coli. In solutions containing a suitable
      concentration of physiological osmolytes, macromolecular crowding promotes the
      GTP-dependent assembly of FtsZ into dynamic two-dimensional polymers that
      disassemble upon GTP depletion. Atomic force microscopy reveals that these FtsZ
      polymers adopt the shape of ribbons that are one subunit thick. When compared
      with the FtsZ filaments observed in vitro in the absence of crowding, the ribbons
      show a lag in the GTPase activity and a decrease in the GTPase rate and in the
      rate of GTP exchange within the polymer. We propose that, in the crowded
      bacterial cytoplasm under assembly-promoting conditions, the FtsZ filaments tend
      to align forming dynamic ribbon polymers. In vivo these ribbons would fit into
      the Z-ring even in the absence of other interactions. Therefore, the presence of
      mechanisms to prevent the spontaneous assembly of the Z-ring in non-dividing
      cells must be invoked.

PMID- 12807908
TI  - Protein 4.1-mediated membrane targeting of human discs large in epithelial cells.
AB  - Human discs large (hDlg) protein binds to protein 4.1R via a motif encoded by an
      alternatively spliced exon located between the SH3 and the C-terminal guanylate
      kinase-like domains. To evaluate the functional significance of protein 4.1R
      binding for subcellular localization of hDlg in vivo, we expressed full-length
      recombinant constructs of two naturally occurring isoforms of hDlg termed hDlg-I2
      and hDlg-I3. The hDlg-I3 but not the hDlg-I2 isoform binds to the FERM (Four.1
      Ezrin-Radixin-Moesin) domain of protein 4.1R in vitro. Upon transient
      transfection into subconfluent Madine-Darby canine kidney (MDCK) epithelial
      cells, the hDlg-I3 fused with the green fluorescent protein accumulated
      predominantly at the plasma membrane of cell-cell contact sites, whereas the hDlg
      I2 fusion protein distributed in the cytoplasm. In contrast, in stably
      transfected confluent MDCK cells, both hDlg-I2 and -I3 isoforms localized
      efficiently to the lateral membrane, consistent with the previous notion that the
      N-terminal domain of hDlg mediates its membrane targeting in polarized epithelial
      cells. We introduced a double mutation (I38A/I40A) into the N-terminal domain of
      hDlg, which disrupted its interaction with DLG2, a key event in the membrane
      targeting of hDlg. Interestingly, the hDlg-I2 isoform harboring the I38A/I40A
      mutation mislocalized from the membrane into cytoplasm. Importantly, the hDlg-I3
      isoform with the same mutation localized efficiently to the membrane of confluent
      MDCK cells. Together, our results demonstrate that in addition to the N-terminal
      targeting domain, the alternatively spliced I3 insertion plays a critical role in
      recruiting hDlg to the lateral membrane in epithelial cells via its interaction
      with protein 4.1R.

PMID- 12807909
TI  - Specific activation of the acetylcholine receptor subunit genes by MyoD family
      proteins.
AB  - Whether the myogenic regulatory factors (MRFs) of the MyoD family can
      discriminate among the muscle gene targets for the proper and reproducible
      formation of skeletal muscle is a recurrent question. We have previously shown
      that, in Xenopus laevis, myogenin specifically transactivated muscle structural
      genes in vivo. In the present study, we used the Xenopus model to examine the
      role of XMyoD, XMyf5, and XMRF4 for the transactivation of the (nicotinic
      acetylcholine receptor) nAChR genes in vivo. During early Xenopus development,
      the expression patterns of nAChR subunit genes proved to be correlated with the
      expression patterns of the MRFs. We show that XMyf5 specifically induced the
      expression of the delta-subunit gene in cap animal assays and in endoderm cells
      of Xenopus embryos but was unable to activate the expression of the gamma-subunit
      gene. In embryos, overexpression of a dominant-negative XMyf5 variant led to the
      repression of delta-but not gamma-subunit gene expression. Conversely, XMyoD and
      XMRF4 activated gamma-subunit gene expression but were unable to activate delta
      subunit gene expression. Finally, all MRFs induced expression of the alpha
      subunit gene. These findings strengthen the concept that one MRF can specifically
      control a subset of muscle genes that cannot be activated by the other MRFs.

PMID- 12807910
TI  - Eps15 homology domain-NPF motif interactions regulate clathrin coat assembly
      during synaptic vesicle recycling.
AB  - Although genetic and biochemical studies suggest a role for Eps15 homology domain
      containing proteins in clathrin-mediated endocytosis, the specific functions of
      these proteins have been elusive. Eps15 is found at the growing edges of clathrin
      coated pits, leading to the hypothesis that it participates in the formation of
      coated vesicles. We have evaluated this hypothesis by examining the effect of
      Eps15 on clathrin assembly. We found that although Eps15 has no intrinsic ability
      to assemble clathrin, it potently stimulates the ability of the clathrin adaptor
      protein, AP180, to assemble clathrin at physiological pH. We have also defined
      the binding sites for Eps15 on squid AP180. These sites contain an NPF motif, and
      peptides derived from these binding sites inhibit the ability of Eps15 to
      stimulate clathrin assembly in vitro. Furthermore, when injected into squid giant
      presynaptic nerve terminals, these peptides inhibit the formation of clathrin
      coated pits and coated vesicles during synaptic vesicle endocytosis. This is
      consistent with the hypothesis that Eps15 regulates clathrin coat assembly in
      vivo, and indicates that interactions between Eps15 homology domains and NPF
      motifs are involved in clathrin-coated vesicle formation during synaptic vesicle
      recycling.

PMID- 12807911
TI  - Assembly of archaeal cell division protein FtsZ and a GTPase-inactive mutant into
      double-stranded filaments.
AB  - We have studied the assembly and GTPase of purified FtsZ from the
      hyperthermophilic archaeon Methanococcus jannaschii, a structural homolog of
      eukaryotic tubulin, employing wild-type FtsZ, FtsZ-His6 (histidine-tagged FtsZ),
      and the new mutants FtsZ-W319Y and FtsZ-W319Y-His6, with light scattering,
      nucleotide analyses, electron microscopy, and image processing methods. This has
      revealed novel properties of FtsZ. The GTPase of archaeal FtsZ polymers is
      suppressed in Na+-containing buffer, generating stabilized structures that
      require GDP addition for disassembly. FtsZ assembly is polymorphic. Archaeal
      FtsZ(wt) assembles into associated and isolated filaments made of two parallel
      protofilaments with a 43 A longitudinal spacing between monomers, and this
      structure is also observed in bacterial FtsZ from Escherichia coli. The His6
      extension facilitates the artificial formation of helical tubes and sheets. FtsZ
      W319Y-His6 is an inactivated GTPase whose assembly remains regulated by GTP and
      Mg2+. It forms two-dimensional crystals made of symmetrical pairs of tubulin-like
      protofilaments, which associate in an antiparallel array (similarly to the known
      Ca2+-induced sheets of FtsZ-His6). In contrast to the lateral interactions of
      microtubule protofilaments, we propose that the primary assembly product of FtsZ
      is the double-stranded filament, one or several of which might form the dynamic Z
      ring during prokaryotic cell division.

PMID- 12807912
TI  - Mammals have two twinfilin isoforms whose subcellular localizations and tissue
      distributions are differentially regulated.
AB  - Twinfilin is a highly conserved actin monomer-binding protein that regulates
      cytoskeletal dynamics in organisms from yeast to mammals. In addition to the
      previously characterized mammalian twinfilin-1, a second protein with
      approximately 65% sequence identity to twinfilin-1 exists in mouse and humans.
      However, previous studies failed to identify any actin binding activity in this
      protein (Rohwer, A., Kittstein, W., Marks, F., and Gschwendt, M. (1999) Eur. J.
      Biochem. 263, 518-525). Here we show that this protein, which we named twinfilin
      2, is indeed an actin monomer-binding protein. Similar to twinfilin-1, mouse
      twinfilin-2 binds ADP-G-actin with a higher affinity (KD = 0.12 microM) than ATP
      G-actin (KD = 1.96 microM) and efficiently inhibits actin filament assembly in
      vitro. Both mouse twinfilins inhibit the nucleotide exchange on actin monomers
      and directly interact with capping protein. Furthermore, the actin interactions
      of mouse twinfilin-1 and twinfilin-2 are inhibited by phosphatidylinositol (4,5)
      bisphosphate. Although biochemically very similar, our Northern blots and in situ
      hybridizations show that these two proteins display distinct expression patterns.
      Twinfilin-1 is the major isoform in embryos and in most adult mouse non-muscle
      cell-types, whereas twinfilin-2 is the predominant isoform of adult heart and
      skeletal muscles. Studies with isoform-specific antibodies demonstrated that
      although the two proteins show similar localizations in unstimulated cells, they
      are regulated by different mechanisms. The small GTPases Rac1 and Cdc42 induce
      the redistribution of twinfilin-1 to membrane ruffles and cell-cell contacts,
      respectively, but do not affect the localization of twinfilin-2. Taken together,
      these data show that mammals have two twinfilin isoforms, which are
      differentially expressed and regulated through distinct cellular signaling
      pathways.

PMID- 12807913
TI  - Mapmodulin/leucine-rich acidic nuclear protein binds the light chain of
      microtubule-associated protein 1B and modulates neuritogenesis.
AB  - We had previously described the leucine-rich acidic nuclear protein (LANP) as a
      candidate mediator of toxicity in the polyglutamine disease, spinocerebellar
      ataxia type 1 (SCA1). This was based on the observation that LANP binds ataxin-1,
      the protein involved in this disease, in a glutamine repeat-dependent manner.
      Furthermore, LANP is expressed abundantly in purkinje cells, the primary site of
      ataxin-1 pathology. Here we focused our efforts on understanding the neuronal
      properties of LANP. In undifferentiated neuronal cells LANP is predominantly a
      nuclear protein, requiring a bona fide nuclear localization signal to be imported
      into the nucleus. LANP translocates from the nucleus to the cytoplasm during the
      process of neuritogenesis, interacts with the light chain of the microtubule
      associated protein 1B (MAP1B), and modulates the effects of MAP1B on neurite
      extension. LANP thus could play a key role in neuronal development and/or
      neurodegeneration by its interactions with microtubule associated proteins.

PMID- 12807914
TI  - The structure of Aip1p, a WD repeat protein that regulates Cofilin-mediated actin
      depolymerization.
AB  - Actin-interacting protein 1 (Aip1p) is a 67-kDa WD repeat protein known to
      regulate the depolymerization of actin filaments by cofilin and is conserved in
      organisms ranging from yeast to mammals. The crystal structure of Aip1p from
      Saccharomyces cerevisiae was determined to a 2.3-A resolution and a final
      crystallographic R-factor of 0.204. The structure reveals that the overall fold
      is formed by two connected seven-bladed beta-propellers and has important
      implications for the structure of Aip1 from other organisms and WD repeat
      containing proteins in general. These results were unexpected because a maximum
      of 10 WD repeats had been reported in the literature for this protein using
      sequence data. The surfaces of the beta-propellers formed by the D-A and B-C
      loops are positioned adjacent to one another, giving Aip1p a shape that resembles
      an open "clamshell." The mapping of conserved residues to the structure of Aip1p
      reveals dense patches of conserved residues on the surface of one beta-propeller
      and at the interface of the two beta-propellers. These two patches of conserved
      residues suggest a potential binding site for F-actin on Aip1p and that the
      orientation of the beta-propellers with respect to one another plays a role in
      binding an actin-cofilin complex. In addition, the conserved interface between
      the domains is mediated by a number of interactions that appear to impart
      rigidity between the two domains of Aip1p and may make a large substrate-induced
      conformational change difficult.

PMID- 12807915
TI  - G beta gamma mediates the interplay between tubulin dimers and microtubules in
      the modulation of Gq signaling.
AB  - Agonist stimulation causes tubulin association with the plasma membrane and
      activation of PLC beta 1 through direct interaction with, and transactivation of,
      G alpha q. Here we demonstrate that G beta gamma interaction with tubulin down
      regulates this signaling pathway. Purified G beta gamma, alone or with
      phosphatidylinositol 4,5-bisphosphate (PIP2), inhibited carbachol-evoked membrane
      recruitment of tubulin and G alpha q transactivation by tubulin. Polymerization
      of microtubules elicited by G beta gamma overrode tubulin translocation to the
      membrane in response to carbachol stimulation. G beta gamma sequestration of
      tubulin reduced the inhibition of PLC beta 1 observed at high tubulin
      concentration. G beta 1 gamma 2 interacted preferentially with tubulin-GDP,
      whereas G alpha q was transactivated by tubulin-GTP. Prenylation of the gamma 2
      polypeptide was required for G beta gamma/tubulin interaction. Both confocal
      microscopy and coimmunoprecipitation studies revealed the spatiotemporal pattern
      of G beta gamma/tubulin interaction during carbachol stimulation of neuroblastoma
      SK-N-SH cells. In resting cells G beta gamma localized predominantly at the cell
      membrane, whereas tubulin was found in well defined microtubules in the cytosol.
      Within 2 min of agonist exposure, a subset of tubulin translocated to the plasma
      membrane and colocalized with G beta. Fifteen min post-carbachol addition,
      tubulin and G beta colocalized in vesicle-like structures in the cytosol. G
      beta/tubulin colocalization increased after pretreatment of cells with the
      microtubule-depolymerizing agent, colchicine, and was inhibited by taxol. Taxol
      also inhibited carbachol-induced PIP2 hydrolysis. It is suggested that G beta
      gamma/tubulin interaction mediates internalization of membrane-associated tubulin
      at the offset of PLC beta 1 signaling. Newly cytosolic G beta gamma/tubulin
      complexes might promote microtubule polymerization attenuating further tubulin
      association with the plasma membrane. Thus G protein-coupled receptors might
      evoke G alpha and G beta gamma to orchestrate regulation of phospholipase
      signaling by tubulin dimers and control of cell shape by microtubules.

PMID- 12807916
TI  - Stimulation of signal transducer and activator of transcription-1 (STAT1)
      dependent gene transcription by lipopolysaccharide and interferon-gamma is
      regulated by mammalian target of rapamycin.
AB  - Mammalian target of rapamycin (mTOR) and phosphatidylinositol 3-kinase (PI3K)
      regulate cell growth, protein synthesis, and apoptosis in response to nutrients
      and mitogens. As an important source of nitric oxide during inflammation, human
      inducible nitric oxide synthase also plays a role in the regulation of cytokine
      driven cell proliferation and apoptosis. The role of mTOR and PI3K in the
      activation of human inducible nitric oxide synthase transcription by cytokines
      and lipopolysaccharide (LPS) was investigated in lung epithelial adenocarcinoma
      (A549) cells. LY294002, a dual mTOR and PI3K inhibitor, blocked human inducible
      nitric oxide synthase (hiNOS) promoter activation and mRNA induction by cytokines
      and LPS in a PI3K-independent fashion. On gene expression analysis, LY294002
      selectively blocked the induction of a subset of 14 LPS/interferon-gamma (IFN
      gamma)-induced genes, previously characterized as signal transducer and activator
      of transcription-1 (STAT1)-dependent. LY294002, but not wortmannin, inhibited
      LPS/IFN-gamma-dependent STAT1 phosphorylation at Ser-727 and STAT1 activity.
      Consistent with dual inhibition of mTOR and PI3K by LY294002, dominant-negative
      mTOR, anti-mTOR small interfering RNA, or rapamycin each inhibited
      phosphorylation of STAT1 only in the presence of wortmannin. LPS/IFN-gamma led to
      the formation of a macromolecular complex containing mTOR, STAT1, as well as
      protein kinase C delta, a known STAT1alpha kinase. Thus, LPS and IFN-gamma
      activate the PI3K and mTOR pathways, which converge to regulate STAT1-dependent
      transcription of pro-apoptotic and pro-inflammatory genes in a rapamycin
      insensitive manner.

PMID- 12807918
TI  - In response to: "Is there an antiaging medicine?".

PMID- 12807917
TI  - Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in
      Jurkat T lymphocytes.
AB  - The loss of intracellular potassium is a pivotal step in the induction of
      apoptosis but the mechanisms underlying this response are poorly understood. Here
      we report caspase-dependent stimulation of potassium channels by the Fas receptor
      in a human Jurkat T cell line. Receptor activation with Fas ligand for 30 min
      increased the amplitude of voltage-activated potassium currents 2-fold on
      average. This produces a sustained outward current, approximately 10 pA, at
      physiological membrane potentials during Fas ligand-induced apoptosis. Both basal
      and Fas ligand-induced currents were blocked completely by toxins that
      selectively inhibit Kv1.3 potassium channels. Kv1.3 stimulation required the
      expression of Fas-associated death domain protein and activation of caspase 8,
      but did not require activation of caspase 3 or protein synthesis. Furthermore,
      Kv1.3 stimulation by Fas ligand was prevented by chronic stimulation of protein
      kinase C with 20 nm phorbol 12-myristate 13-acetate during Fas ligand treatment,
      which also blocks apoptosis. Thus, Fas ligand increases Kv1.3 channel activity
      through the same canonical apoptotic signaling cascade that is required for
      potassium efflux, cell shrinkage, and apoptosis.

PMID- 12807919
TI  - What fecundity patterns indicate about aging and longevity: insights from
      Drosophila studies.
AB  - The age pattern of fecundity is represented as a result of a superposition of two
      processes: the genetic fecundity program encoded in the organism's reproductive
      machinery and senescence of the reproductive system. Accumulation of oxidative
      damage produces the energy decline, which could potentially be used in
      reproduction. As a result, the age-declining process arises in the reproductive
      machinery at a critical age. We show that this mechanism is common for different
      species. It establishes a connection between the decline of organism vitality and
      reproductive senescence. We suggest a parametric description of a fecundity
      pattern that allows for prediction of reproductive longevity. We apply the
      approach to Drosophila studies to analyze the relation between fecundity and
      survival. We show that fecundity patterns may predict a mean life span in
      Drosophila under specified environmental conditions.

PMID- 12807920
TI  - Differential patterns of age-related mortality increase in middle age and old
      age.
AB  - It is often assumed that aging is a uniform process throughout adulthood because
      of the approximately linear increase of logarithmic mortality. We explored this
      assumption by analyzing cause-specific mortality increases in France (1979-1994).
      Rising rapidly at ages 30-54 years ("middle age") are death rates from malignant
      neoplasms at various sites, acute myocardial infarction, hypertensive disease,
      and liver cirrhosis. Steeply increasing at 65-89 years ("old age") are death
      rates from certain infectious diseases, particularly of the respiratory system;
      certain types of accidents; nonalcoholic mental disorders (probably due mainly to
      Alzheimer's disease and senile dementia); heart failure; cerebrovascular disease;
      and some "vague" categories. The processes at work may be fundamentally different
      in these two life history stages, such that the mortality rise in middle age
      reflects specific chronic diseases that develop prematurely in some high-risk
      individuals, whereas the mortality increase in old age is dominated by senescent
      processes that eventually raise the vulnerability of almost all individuals to
      multiple pathologies.

PMID- 12807921
TI  - The effect of caloric restriction on glycation and glycoxidation in skin collagen
      of nonhuman primates.
AB  - The accumulation of Maillard reaction products increases with age in long-lived
      proteins and can be retarded by caloric restriction. Here we determined whether
      caloric restriction inhibits formation of glycation and glycoxidation products in
      skin collagen of squirrel and rhesus monkeys between 1990-1997. Restricted
      monkeys (n = 11, n = 30, respectively) were maintained at 70% of caloric intake
      of controls (n = 25, n = 32, respectively). Glycation was assessed by furosine
      and glycoxidation by pentosidine and carboxymethyl-lysine. With age, the rate of
      furosine formation moderately but nonsignificantly (p >.05) increased in both
      control monkey groups. It significantly (p =.011) decreased in the caloric
      restricted rhesus, but not squirrel monkeys. Caloric restriction did not
      significantly decrease the pentosidine or carboxymethyl-lysine rates in either
      species of monkeys. These results suggest that caloric restriction, when
      maintained long-term in nonhuman primates, tends to decrease glycation, but not
      glycoxidation.

PMID- 12807922
TI  - Intracerebral aneurysms: a review with special attention to geriatric aspects.
AB  - Rupture of an intracranial aneurysm (ICA) remains a devastating complication
      associated with a high degree of morbidity and mortality. In the past 2 decades,
      older people were often excluded from active treatment on the unique basis of
      their chronological age. Recent developments of less-invasive techniques for the
      diagnosis and treatment of ruptured and unruptured ICAs suggest that this
      fatalistic attitude toward older patients should be reconsidered. Furthermore,
      taking into account the heterogeneity of the elderly population, the use of a
      comprehensive geriatric assessment approach, based on a multidisciplinary
      evaluation, appears particularly helpful in proposing the optimal treatment
      strategy for each older patient. This article reviews the geriatric features of
      epidemiological, physiopathological, as well as clinical and therapeutic aspects
      of ruptured and unruptured ICAs.

PMID- 12807923
TI  - Changes in postural stability in women aged 20 to 80 years.
AB  - BACKGROUND: A study of postural stability was undertaken to identify the
      relationship between vision and support surface across age decades. Understanding
      when reliance on vision for postural stability emerges and the support conditions
      contributing to this instability may provide the evidence required to introduce
      falls-prevention strategies in younger age decades. METHODS: We measured postural
      stability in 453 women aged 20 to 80 years using the Balance Master force-plate
      system while the women performed the modified Clinical Test for the Sensory
      Interaction and Balance (firm and foam surfaces, eyes open and closed) and the
      Single-Limb Stance Test (eyes open and closed). RESULTS: Women in their 60s and
      70s were more unstable than younger women in bilateral stance on a firm surface
      with the eyes closed. This instability was evident from the 50s when a foam
      surface was introduced and from the 40s when single-limb stance was tested with
      eyes closed. A further decline in stability was demonstrated for each subsequent
      decade when the eyes were closed in single-limb stance. CONCLUSIONS: Age, visual
      condition, and support surface were significant variables influencing postural
      stability in women. Reliance on vision for postural stability was evident for
      women from the 40s when single-limb stance was tested, from the 50s when
      bilateral stance on foam was tested, and from the 60s when a firm surface was
      used. The cause(s) of this decline in stability requires further investigation,
      and screening for postural instability between the ages of 40 and 60 is
      advocated.

PMID- 12807924
TI  - Cognitive function and incidence of stroke in older Mexican Americans.
AB  - BACKGROUND: Given the high prevalence of cognitive impairment in older Mexican
      Americans and limited longitudinal research examining cognitive function in this
      ethnic group, we conducted a study examining whether cognitive impairment is a
      risk factor for new onset of stroke among older Mexican Americans. METHODS: We
      performed a prospective cohort study of 2682 Mexican Americans aged 65 years and
      older living in the southwestern United States. For subjects with no prior
      history of stroke and who completed the Mini-Mental State Examination (MMSE) at
      baseline, stroke incidence was assessed after 2, 5, and 7 years of follow-up.
      RESULTS: In Cox proportional regression models, MMSE score at baseline predicted
      risk of incident stroke over a 7-year follow-up period. For the unadjusted model,
      subjects with an MMSE score of 21 or higher were half as likely to report stroke
      at follow-up (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.35-0.69; p
      <.001) compared with those with a score of less than 21. We found similar results
      after controlling for relevant risk factors for stroke including age, gender,
      smoking status, education, body mass index, diabetes, heart attack, systolic
      blood pressure, and depressive symptoms (HR, 0.54; 95% CI, 0.38-0.77; p =.001).
      Additionally, each 1-point increase in MMSE score was associated with a 5%
      reduction in risk (HR, 0.95; 95% CI, 0.92-0.99; p =.01). CONCLUSIONS: Increasing
      MMSE score is associated with a decreasing incidence of stroke in older Mexican
      Americans. This study highlights the need for a more aggressive focus on
      identifying and addressing cognitive decline in the Mexican American population.

PMID- 12807925
TI  - Bilateral index expressions and iEMG activity in older versus young adults.
AB  - BACKGROUND: This study investigated the hypothesis that expressions of maximal
      and submaximal bilateral indices would not differ between older and young
      participants. METHODS: Twenty older (73.3 +/- 4.4 years) and 21 younger (22.4 +/-
      0.9 years) participants performed maximal voluntary isometric contractions of the
      elbow flexor muscles, using the right arm only, left arm only, and both arms
      simultaneously. The participants were asked to repeat these contractions at what
      they perceived to be 25%, 50%, and 75% of their maximal voluntary isometric
      contraction levels. RESULTS: Significant bilateral deficits (p <.05), defined as
      a bilateral index <0, existed at maximal and submaximal intensities, but the
      submaximal deficits (14-18%) were larger than the maximal deficits (11%).
      Normalized integrated electromyographic values tended to be higher for unilateral
      trials than for bilateral trials at all submaximal intensity levels. There were
      no significant differences between the older and young participants. CONCLUSIONS:
      Despite the decrease in the size of fast twitch motor units associated with
      aging, bilateral deficits exist in older adults, do not differ from those
      observed for younger adults, and remain larger for submaximal intensities.

PMID- 12807926
TI  - A comparative study of rehabilitation outcomes of elderly hip fracture patients:
      the advantage of a comprehensive orthogeriatric approach.
AB  - BACKGROUND: The optimal setting and design of a comprehensive treatment for
      elderly hip fracture patients is unknown. The aims of this study were to compare
      the functional outcomes associated with an innovative comprehensive single-step
      (geriatric-based) and classic double-step (orthopedic-based) treatment of such
      patients. METHODS: This is a partially concurrent prospective study, taking place
      in the orthogeriatric unit of a department of geriatric rehabilitation, in a
      large urban academic freestanding hospital. The participants were 336 consecutive
      elderly people, admitted for surgery of extracapsular or intracapsular hip
      fracture. 204 patients were admitted to the department of orthopedic surgery and
      transferred, shortly after surgery, to the orthogeriatric ward for ongoing
      rehabilitation (ORT group). Another 116 patients were admitted directly to a
      geriatric-based orthogeriatric ward, and they received surgical, medical, and
      rehabilitation treatment within the same facility (ORTGER group). The main
      outcome measures were length of stay, absolute functional gains of the motor
      functional independence measure (FIM), and relative functional motor gains
      according to the Montebello rehabilitation factor score. Successful
      rehabilitation was defined as relative functional gain >.5. RESULTS: 320 patients
      were included in the final analysis. The two groups were similar, yet ORT-group
      patients were somewhat younger (p <.02) and were cognitively better preserved (p
      <.01). Admission cognitive FIM was the strongest positive predictive factor
      associated with successful rehabilitation (odds ratio = 2.45, 95% confidence
      interval 1.89-3.31, and p <.001). Significant improvement of total FIM scores
      occurred during rehabilitation in both groups. The relative functional gain was
      similar in the two groups, but total hospital length of stay was 5 days shorter
      in the ORTGER group (p <.01). After the effect of age, sex, length of stay,
      fracture type, and cognition at onset of the rehabilitation period were adjusted
      for, patients of the ORTGER group had a twofold chance for successful
      rehabilitation, compared with ORT-group patients (odds ratio = 1.97, 95%
      confidence interval 1.09-3.65, and p =.03). CONCLUSIONS: The functional outcome
      of elderly hip fracture patients is better for those treated in the
      orthogeriatric setting, as compared with the common two-steps model of orthopedic
      surgery followed by transfer to a geriatric rehabilitation facility.

PMID- 12807927
TI  - Presence of behavioral and psychological symptoms predicts nursing home placement
      in community-dwelling elders with cognitive impairment in univariate but not
      multivariate analysis.
AB  - BACKGROUND: The role of behavioral and psychological symptoms as an independent
      risk factor of nursing home placement (NHP) in cognitively impaired elders has
      been controversial. METHODS: A community sample of 449 cognitively impaired
      elders and their knowledgeable informants (KIs) was followed for 1 year. Subjects
      were classified as having dementia (n=330) or mild cognitive impairment (MCI)
      (n=119) using a neuropsychiatric battery of 4 tests. Subject characteristics
      (behavioral and psychological symptoms, demographic, health related, and health
      services use) and KI characteristics were entered into the Cox proportional
      hazard regression analysis. RESULTS: The incidence rate of NHP was 8.9%. At
      baseline, 57.7% of subjects had at least 1 behavioral and psychological symptom.
      Presence of these symptoms was associated with shorter time to NHP only in a
      univariate analysis. Other factors significant in the multivariate Cox modeling
      were being white (hazard ratio [HR] = 2.17), having fair or poor physical health
      rating (HR= 2.12), having greater numbers of difficulties with activities of
      daily living (HR = 1.46), and having a physician's diagnosis of dementia (HR =
      6.76). An interaction was found between the last 2 variables (HR = 0.59),
      indicating that among those with a diagnosis of dementia, a greater number of
      difficulties with activities of daily living delayed time to NHP. KI
      characteristics were not associated with NHP. CONCLUSIONS: Behavioral and
      psychological symptoms were common, but having these symptoms was not an
      independent risk factor of NHP. Caregiver characteristics may not play as
      important a role in determining NHP as subject characteristics. Interventions
      aimed at improving or maintaining physical or cognitive functioning may have
      better chances of delaying NHP.

PMID- 12807928
TI  - Habitual walking and its correlation to better physical function: implications
      for prevention of physical disability in older persons.
AB  - BACKGROUND: Our objective was to determine the association between participation
      in habitual physical activity (including walking, shopping, and indoor and
      outdoor activities) and leisure-time or sports activities on physical performance
      and fitness in older persons. METHODS: In an observational study, 123
      predominantly ethnic Chinese participants aged 50 years and older were recruited
      from a health promotion program. Main outcome measures were bioelectric impedance
      for body fat composition, peak oxygen consumption (VO(2)max), gait speed,
      handgrip strength, and chair rise time. RESULTS: The mean age of participants was
      years. Those with a higher self-reported walking level had a better VO(2)max;
      every 1 minute per day increase in habitual walking increases VO(2)max by 0.096
      (ml/kg)/min (95% confidence interval [CI] 0.027-0.165, p=.007) and is possibly
      associated with a faster gait speed; (95% CI 0.000-0.005, p=.078). There is an
      age-related rise in body fat composition, decline in VO(2)max, and slower chair
      rise time. Men had a lower body fat composition, better VO(2)max, and stronger
      handgrip. CONCLUSIONS: Habitual walking may impart important health benefits in
      terms of improvement in physical performance, fitness, and its implications for
      the prevention of physical disability in older adults. This also reinforces the
      theory that low- to moderate-intensity activities may improve cardiorespiratory
      fitness. There is an inevitable physiological age-related decline in physical
      fitness.

PMID- 12807929
TI  - Effect of plasma lipoproteins on natural killer cell activity in the elderly
      population.
AB  - BACKGROUND: Natural killer (NK) cells possess spontaneous cytotoxicity against
      tumors and virus-infected cells to play a major role in immunosurveillance and
      defense against the development of cancer, as well as bacterial and viral
      infections. The role of plasma lipoproteins in atherogenesis is well recognized,
      but the physiological relevance of their immunoregulatory properties is still
      questioned. In particular, it is unknown whether hypercholesterolemia should be
      considered a risk factor for diminished immunity in old age. METHODS: To evaluate
      effects of plasma lipoprotein levels on immune function, we assessed the relation
      between plasma lipoprotein profiles and NK cell activity. NK cell activity was
      assayed by release of (51)Cr from K562 target cells, and concurrent plasma
      lipoprotein levels were measured in 47 samples of elderly males (mean age +/- SD,
      66.6 +/- 1.7 years). RESULTS: Univariate regression analyses revealed direct
      relations between NK cell activity and high-density lipoprotein cholesterol
      (r=.46, p<.001), apolipoprotein (Apo) A-1 (r=.48, p<.001), and Apo A-2 (r=.46,
      p<.005). In addition, multiple regression analyses showed a direct independent
      relation between NK cell activity and Apo A-1 (b=0.32+/-0.09 mg/dl, beta=0.48,
      and p <.001). CONCLUSION: NK cell activity is related directly to plasma Apo A-1
      levels in elderly subjects. The mechanisms of this interaction are unknown, but
      Apo A-1 contributes to the composition of the antiatherogenic fraction of high
      density lipoprotein and could also defend against infectious and malignant
      disease through a potential for NK cell activity.

PMID- 12807930
TI  - Communication between identical twins: health behavior and social factors are
      associated with longevity that is greater among identical than fraternal U.S.
      World War II veteran twins.
AB  - BACKGROUND: Longevity is greater for identical twins than for fraternal twins
      from the same population. Factors that are explanatory for this difference are
      not known. METHODS: Multivariate survival analysis is applied to current
      mortality data for 26,974 male twins with known zygosities of the National
      Academy of Science-National Research Council World War II Veteran Twins Registry,
      and this analysis is applied to their health and social behavior and personal
      histories, as collected from two survey questionnaires distributed in 1967 and
      1983 (with 14,300 and 9475 responses received, respectively). To explain this
      difference in longevity, social, health, and personal history factors are
      evaluated for associations with longevity. RESULTS: Survival functions of
      identical and fraternal twins differed significantly (p<.0001). Median lifetimes
      were 82 years for identical and 80.5 years for fraternal twins. The correlation
      between lifetimes of identical twin partners was greater than that of fraternal
      twins. For identical but not for fraternal twins, the risk of mortality was
      significantly lower for twin partners who communicated 1 or more times per month,
      compared with those who communicated less frequently (relative risk.80, 95%
      confidence interval 0.68-0.94, p=.008, with control for other factors associated
      with longevity: smoking, exercise, a current marriage, living with both parents
      until age 15 or older, and having a live co-twin). Distributions of
      communication, exercise level, and smoking prevalence were more beneficial with
      regard to longevity for identical than for fraternal twins as a group.
      CONCLUSIONS: Frequent communication between identical but not fraternal twin
      partners, and both level of exercise and prevalence of smoking, distributed more
      beneficially in terms of longevity for identical compared with fraternal twins,
      are explanatory for the greater longevity of identical than fraternal twins.

PMID- 12807931
TI  - Elderly diabetics with peripheral arterial disease and no coronary artery disease
      have a higher incidence of new coronary events than elderly nondiabetics with
      peripheral arterial disease and prior myocardial infarction treated with statins
      and with no lipid-lowering drug.
AB  - BACKGROUND: We report data showing the incidence of new coronary events in
      diabetics with prior myocardial infarction (MI), nondiabetics with prior MI,
      diabetes with no coronary artery disease (CAD), and nondiabetics with no CAD who
      were treated with and without statins. METHODS: We investigated-in an
      observational prospective study of 274 diabetics and 386 nondiabetics with
      peripheral arterial disease, mean age years, and a serum low-density lipoprotein
      cholesterol level of >/=125 mg/dl-the incidence of new coronary events in
      diabetics with prior MI, nondiabetics with prior MI, diabetics with no CAD, and
      nondiabetics with no CAD who were treated with and without statins. Follow-up was
      months. RESULTS: In patients treated with statins, the incidence of new coronary
      events was 73% in diabetics with prior MI (group 1), 37% in nondiabetics with
      prior MI (group 2), 57% in diabetics with no CAD (group 3), and 27% in
      nondiabetics with no CAD (group 4). In patients treated with no lipid-lowering
      drug, the incidence of new coronary events was 91% in diabetics with prior MI
      (group 5), 72% in nondiabetics with prior MI (group 6), 86% in diabetics with no
      CAD (group 7), and 52% in nondiabetics with no CAD (group 8). Significant p
      values were p<.0001 for group 1 versus 2, group 7 versus 8, and group 2 versus 6;
      p=.0006 for group 3 versus 4; p=.0007 for group 3 versus 7; p=.001 for group 5
      versus 6; p=.002 for group 4 versus 8; p=.003 for group 1 versus 5; p=.015 for
      group 2 versus 3; and p=.047 for group 6 versus 7. CONCLUSIONS: In patients
      treated with and without statins, diabetics with no CAD had a higher incidence of
      new coronary events than did nondiabetics with prior MI.

PMID- 12807932
TI  - Dose-intense paclitaxel: deja vu all over again?

PMID- 12807933
TI  - Functional imaging in phase I studies: decorations or decision making?

PMID- 12807934
TI  - Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and
      pharmacokinetic results.
AB  - PURPOSE: A phase I trial was performed with combretastatin A4 phosphate (CA4P), a
      novel tubulin-binding agent that has been shown to rapidly reduce blood flow in
      animal tumors. PATIENTS AND METHODS: The drug was delivered by a 10-minute weekly
      infusion for 3 weeks followed by a week gap, with intrapatient dose escalation.
      Dose escalation was accomplished by doubling until grade 2 toxicity was seen. The
      starting dose was 5 mg/m2. RESULTS: Thirty-four patients received 167 infusions.
      CA4P was rapidly converted to the active combretastatin A4 (CA4), which was
      further metabolized to the glucuronide. CA4 area under the curve (AUC) increased
      from 0.169 at 5 mg/m2 to 3.29 micromol * h/L at 114 mg/m2. The mean CA4 AUC in
      eight patients at 68 mg/m2 was 2.33 micromol * h/L compared with 5.8 micromol *
      h/L at 25 mg/kg (the lowest effective dose) in the mouse. The only toxicity that
      possibly was related to the drug dose up to 40 mg/m2 was tumor pain. Dose
      limiting toxicity was reversible ataxia at 114 mg/m2, vasovagal syncope and motor
      neuropathy at 88 mg/m2, and fatal ischemia in previously irradiated bowel at 52
      mg/m2. Other drug-related grade 2 or higher toxicities seen in more than one
      patient were pain, lymphopenia, fatigue, anemia, diarrhea, hypertension,
      hypotension, vomiting, visual disturbance, and dyspnea. One patient at 68 mg/m2
      had improvement in liver metastases of adrenocortical carcinoma. CONCLUSION: CA4P
      was well tolerated in 14 of 16 patients at 52 or 68 mg/m2; these are doses at
      which tumor blood flow reduction has been recorded.

PMID- 12807935
TI  - Assessment of pharmacodynamic vascular response in a phase I trial of
      combretastatin A4 phosphate.
AB  - PURPOSE: Clinical evaluation of novel agents that target tumor blood vessels
      requires pharmacodynamic end points that measure vascular damage. Positron
      emission tomography (PET) was used to measure the effects of the vascular
      targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue
      perfusion and blood volume. PATIENTS AND METHODS: Patients with advanced solid
      tumors were enrolled onto part of a phase I, accelerated-titration, dose
      escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney
      were investigated. Tissue perfusion was measured using oxygen-15 (15O)-labeled
      water and blood volume was measured using 15O-labeled carbon monoxide (C15O).
      Scans were performed immediately before, and 30 minutes and 24 hours after the
      first infusion of each dose level of CA4P. All statistical tests were two sided.
      RESULTS: PET data were obtained for 13 patients with intrapatient dose
      escalation. Significant dose-dependent reductions were seen in tumor perfusion 30
      minutes after CA4P administration (mean change, -49% at >or= 52 mg/m2; P =.0010).
      Significant reductions were also seen in tumor blood volume (mean change, -15% at
      >or= 52 mg/m2; P =.0070). Although by 24 hours there was tumor vascular recovery,
      for doses >or= 52 mg/m2 the reduction in perfusion remained significant (P
      =.013). Thirty minutes after CA4P administration borderline significant changes
      were seen in spleen perfusion (mean change, -35%; P =.018), spleen blood volume
      (mean change, -18%; P =.022), kidney perfusion (mean change, -6%; P =.026), and
      kidney blood volume (mean change, -6%; P =.014). No significant changes were seen
      at 24 hours in spleen or kidney. CONCLUSION: CA4P produces rapid changes in the
      vasculature of human tumors that can be assessed using PET measurements of tumor
      perfusion.

PMID- 12807936
TI  - Combretastatin A4 phosphate has tumor antivascular activity in rat and man as
      demonstrated by dynamic magnetic resonance imaging.
AB  - PURPOSE: Combretastatin A4 phosphate (CA4P) is a novel vascular targeting agent.
      Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) studies were
      performed to examine changes in parameters related to blood flow and vascular
      permeability in tumor and normal tissue after CA4P treatment. MATERIALS AND
      METHODS: Changes in kinetic DCE-MRI parameters (transfer constant [Ktrans] and
      area under contrast medium-time curve [AUC]) over 24 hours after treatment with
      CA4P were measured in 18 patients in a phase I trial and compared with those
      obtained in the rat P22 carcinosarcoma model, using the same imaging technique.
      Rats were treated with 30 mg/kg of CA4P; patients received escalating doses from
      5 to 114 mg/m2. RESULTS: A similar pattern and time course of change in tumor and
      normal tissue parameters was seen in rats and humans. Rat tumor Ktrans was
      reduced by 64% 6 hours after treatment with CA4P (30 mg/kg). No significant
      reductions in kidney or muscle parameters were seen. Significant reductions were
      seen in tumor Ktrans in six of 16 patients treated at >or= 52 mg/m2, with a
      significant group mean reduction of 37% and 29% at 4 and 24 hours, respectively,
      after treatment. The mean reduction in tumor initial area under the gadolinium
      diethylenetriamine pentaacetic acid concentration-time curve (AUC) was 33% and
      18%, respectively, at these times. No reduction was seen in muscle Ktrans or in
      kidney AUC in group analysis of the clinical data. CONCLUSION: CA4P acutely
      reduces Ktrans in human as well as rat tumors at well-tolerated doses, with no
      significant changes in kidney or muscle, providing proof of principle that this
      drug has tumor antivascular activity in rats and humans.

PMID- 12807938
TI  - Future Directions in Epidemiologic and Preventive Research on Human
      Papillomaviruses and Cancer. Proceedings of a workshop. Bethesda, Maryland, USA,
      June 2002.

PMID- 12807937
TI  - Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by
      filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer:
      an intergroup study.
AB  - PURPOSE: To determine if increasing the dose of paclitaxel increases the
      probability of clinical response, progression-free survival, or overall survival
      in women who have persistent or recurrent ovarian cancer, and whether doubling
      the dose of prophylactic filgrastim accompanying the higher paclitaxel dose
      decreases the frequency of neutropenic fever. PATIENTS AND METHODS: Consenting
      patients with persistent, recurrent, or progressing ovarian cancer, despite first
      line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel
      135 mg/m2, 175 mg/m2, or 250 mg/m2 over 24 hours every 3 weeks. Patients
      receiving paclitaxel 250 mg/m2 were also randomly assigned to 5 or 10 microg/kg
      of filgrastim per day subcutaneously. RESULTS: Accession to the paclitaxel 135
      mg/m2 arm was closed early. Among the 271 patients on the other regimens with
      measurable disease, partial and complete response on paclitaxel 250 mg/m2 (36%)
      was significantly higher than on 175 mg/m2 (27%, P =.027). This difference was
      more evident among patients who never responded to prior platinum. However,
      progression-free and overall survival results were similar. The median durations
      of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250
      mg/m2, respectively. Thrombocytopenia, neuropathy, and myalgia were greater with
      paclitaxel 250 mg/m2 (P <.05). The incidence of neutropenic fever after the first
      cycle of paclitaxel 250 mg/m2 was 19% and 18% on the 5-microg/kg and 10-microg/kg
      filgrastim dose, respectively (22% for paclitaxel 175 mg/m2 without filgrastim).
      CONCLUSION: Paclitaxel exhibits a dose effect with regard to response rate, but
      there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2
      plus filgrastim. Doubling the filgrastim dose from 5 to 10 microg/kg did not
      reduce the probability of neutropenic fever after high-dose paclitaxel.

PMID- 12807939
TI  - Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of
      causality.
AB  - Cervical cancer remains the second most common cancer in women worldwide and the
      most frequent in developing countries. Pre-neoplasic cervical lesions represent
      an additional burden in countries where screening is widespread. The human
      papillomavirus (HPV) prevalence and type distribution in normal smears and in
      cancer specimens are being described and show relatively small international
      variation. State-of-the-art detection techniques have unequivocally shown that
      HPV-DNA can be detected in 95% to 100% of adequate specimens of cervical cancer,
      supporting the claim that HPV is the necessary cause. The odds ratios for
      cervical cancer related to a cross sectional detection of HPV-DNA range from 50
      to several hundred in all studies. The risk for any of 15 high-risk types is not
      statistically different from the risk reported for HPV16. The estimates of the
      attributable fraction range from 90% to 98%. Additional work should be done in
      providing information on incidence of cervical cancer and on HPV infection in
      areas where the disease is common. Theoretical work including modeling of the
      incidence could be of potential use in the evaluation of the existing and novel
      preventive strategies. Research is currently being conducted on the mechanisms of
      HPV carcinogenesis. These include the determinants of the systemic and cellular
      immune response to the viral infection, the interaction between the host and the
      virus and the relevance of the different strains and variants of the HPV viral
      types. Technology developments in this area suitable for epidemiological studies
      are needed.

PMID- 12807940
TI  - Chapter 2: Natural history of anogenital human papillomavirus infection and
      neoplasia.
AB  - This chapter suggests promising areas of future epidemiologic research on human
      papillomavirus (HPV) and anogenital cancer, organized around our understanding of
      cervical carcinogenesis. The major steps in cervical carcinogenesis include HPV
      infection, HPV persistence over a certain period of time, progression to
      precancer, and invasion. Backward steps include clearance of HPV infection and
      regression of precancer. Additional studies of incident HPV infections among
      virgins initiating sexual activity could clarify the earliest aspects of
      transmission and immune response. Research on older women and their male partners
      should focus on understanding the determinants of varying age-specific HPV
      prevalence curves and underlying dynamics of viral persistence, clearance, and
      latency. It will be particularly important for epidemiologists to define HPV
      persistence rigorously in order to guide clinical management and vaccine trials.
      Intensive longitudinal studies that collect visual, microscopic (cytologic and
      histologic), and molecular data will be needed to understand the fate of
      individual HPV infections and to clarify whether multiple, concurrent infections
      act independently on the cervix. Case-control designs will be useful mainly in
      searching for new biomarkers of risk of progression among HPV-infected women that
      could then be validated prospectively. Prospective confirmation is also needed
      for the etiologic cofactors established by case-control studies of invasive
      cervical cancer. Much of the knowledge about cervical cancer might apply to anal
      neoplasia. Epidemiologic studies of other genital tumors such as penile neoplasia
      are still needed, but multicentric groups must place great emphasis on
      measurement technology, given the difficulty in obtaining reliable comprehensive
      measurements.

PMID- 12807941
TI  - Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity, oral
      contraceptives, and tobacco smoking.
AB  - It is now well established that infection with oncogenic human papillomavirus
      (HPV) types is the necessary cause of cervical cancer (CC) and its immediate
      precursor cervical intraepithelial neoplasia 3. However, HPV infection alone may
      not be sufficient to cause CC, and other exogenous and endogenous factors may
      exist that, in conjunction with HPV, influence the risk of progression from
      cervical HPV infection to CC. In this chapter, we review the evidence for the
      role of parity, oral contraceptive (OC) use, and tobacco smoking in CC. We also
      discuss limitations and methodologic problems encountered in assessing available
      data and outline recommendations for future research. Based on key studies on
      high-grade squamous intraepithelial lesions (HSILs) and CC conducted among HPV
      positive women, it can be concluded that high parity, smoking, and less
      consistently long-term OC use are cofactors that may modulate the risk of
      progression from HPV infection to HSIL/CC. From a public health point of view,
      parity seems to be the behavioral cofactor explaining the highest proportion of
      CC cases among HPV-infected women. Smoking and long-term OC use may have a
      similar impact in populations that are heavily exposed to HPV and to these
      cofactors. Large prospective and retrospective cohort studies of HSIL and CC
      among middle-aged women in which several markers of HPV exposure are used and HPV
      persistence is documented would be valuable to study the role of these and other
      cofactors in HPV carcinogenesis. If confirmed, our conclusions may imply that
      multiparous women, women who are smokers, and women on long-term OC use may need
      closer surveillance for cytologic abnormalities and HPV infections than women in
      the general population.

PMID- 12807942
TI  - Chapter 4: Genital tract infections, cervical inflammation, and antioxidant
      nutrients--assessing their roles as human papillomavirus cofactors.
AB  - Cervical infections by approximately 15 human papillomavirus (HPV) types are the
      necessary cause of cervical cancer and its immediate precursor lesions. However,
      oncogenic HPV infections are usually benign and usually resolve within 1-2 years.
      A few of these infections persist and progress to cervical precancer and cancer.
      A number of cervical factors, such as infection by sexually transmitted pathogens
      other than HPV, cervical inflammation, and antioxidant nutrients, may influence
      the natural history of HPV infection along the pathways of persistence and
      progression or resolution. We examine the possible roles of these HPV cofactors
      in cervical carcinogenesis and discuss new methodologies that may enable
      researchers to measure relevant markers of the cervical microenvironment in which
      these cofactors may be active.

PMID- 12807943
TI  - Chapter 5: Viral and host factors in human papillomavirus persistence and
      progression.
AB  - Understanding the interdependent roles that host and viral factors play in
      cervical cancer pathogenesis is important for distinguishing women at the highest
      risk of human papillomavirus (HPV) persistence and progression to cervical
      cancer. Ongoing research on viral factors such as viral variants is providing
      important clues regarding HPV oncogenesis; the comprehensive characterization of
      the HPV genome and the function of viral genes by HPV type and variant will
      further this understanding. Although the biologic importance of viral integration
      and viral load measurements in cervical neoplasia is still being debated,
      available data are difficult to interpret because of methodologic limitations; to
      sufficiently address the importance of these events will require further methods
      validation and subsequent application in epidemiologic studies. Continued and
      expanded investigation of host immune responses-humoral, cellular, and innate
      immunity-should specifically address the outcomes of HPV persistence and
      progression to cervical cancer. Molecularly based assays paired with functional
      assays will be integral toward the identification and validation of key immune
      pathways and genes specifically relevant to cervical cancer pathogenesis. Novel
      technologies such as gene expression microarrays will further allow comprehensive
      identification of relevant genes that are important at various stages of cervical
      pathogenesis. The study of viral and host factors will undoubtedly lead to
      markers that may hold diagnostic and/or prognostic value; the clinical validity
      and utility of these molecular events will, therefore, need to be carefully
      assessed before implementation in a population setting.

PMID- 12807944
TI  - Chapter 6: Immunosuppression and co-infection with HIV.
AB  - Individuals with immunosuppression caused by HIV infection or organ
      transplantation are at increased risk of human papillomavirus (HPV)-associated
      anogenital cancers compared with age-matched healthy individuals. The exact role
      of immunosuppression in conferring increased risk is not known. Although it is
      unknown which stages of progression from dysplasia to cancer are most affected by
      immunosuppression, current data suggest that immunosuppression is most strongly
      associated with the early stages of dysplasia, and that progression to cancer per
      se is not associated with immunosuppression. Studies to determine this
      relationship in detail are hampered by the paucity of precise biomarkers of cell
      mediated immune response to HPV. This chapter will address these and other issues
      to provide a better understanding of the biology of HPV infection among
      immunocompromised individuals. Questions remain about the biology of HPV
      infection among immunocompromised HIV-negative individuals (e.g., transplant
      patients) compared with those who are HIV-positive; the impact of highly active
      antiretroviral therapy on the natural history of anogenital dysplasia and cancer
      among those who are HIV-positive, and whether the biology of specific HPV types
      is the same in HIV-positive as in HIV-negative individuals. Understanding HPV
      infection in those who are immunocompromised offers the potential to better
      understand its pathobiology in the putatively immunocompetent host.

PMID- 12807945
TI  - Chapter 7: Human papillomavirus and cancer of the upper aerodigestive tract.
AB  - We discuss current evidence of the role of human papillomavirus (HPV) in some
      cancers of the upper aerodigestive tract, including the oral cavity, the pharynx,
      and the larynx. Cancers of the oral cavity and the pharynx are associated mainly
      with tobacco and alcohol exposure, but there is evidence from case series, from
      case-control studies, and from cohort studies that HPV plays a role in a fraction
      of these cancers, particularly cancer in the oropharynx and tonsil. The HPV type
      most commonly associated with cancers in these locations is HPV 16. Laboratory
      evidence indicates that the virus is integrated and that HPV oncogenes are
      transcriptionally active in these tumors. Many aspects of the association remain
      to be investigated, including the epidemiology and natural history of HPV
      infection in the mouth, the role of cofactors, and the potential use of HPV
      testing and vaccines in the prevention of these tumors. An analogous role for the
      virus at other anatomic sites in the upper aerodigestive tract such as the larynx
      is less clear. The relationship between HPV infection and laryngeal cancer is of
      particular interest, given that recurrent respiratory papillomatosis is clearly
      caused by benign proliferative growths induced by HPV 6 or 11 infection of the
      laryngeal epithelium. Although HPV genomic DNA has been detected in a proportion
      of laryngeal cancers and despite the many efforts made during the last 15 years,
      there is not yet compelling evidence that HPV plays a substantial role in
      laryngeal cancer.

PMID- 12807946
TI  - Chapter 8: Human papillomavirus and skin cancer.
AB  - A high prevalence of human papillomavirus (HPV) DNA, particularly in squamous
      cell skin carcinoma of immunosuppressed but also of immunocompetent patients, has
      renewed great interest in a possible etiologic role of HPV in nonmelanoma skin
      cancer. It is difficult, however, to interpret these findings against a
      background of low-level infections with multiple HPV types from supergroup B
      (HPV4-related and epidermodysplasia verruciformis [EV] HPV), probably acquired by
      everyone early in and throughout life. Thus far, no high-risk HPV types have been
      identified. Because of the low copy numbers of HPV DNA in skin cancers, probably
      not every tumor cell contains a viral genome, which is compatible with cutaneous
      HPV being possibly important for tumor initiation and progression, but not for
      maintenance of the malignant phenotype. The question with regard to high-risk
      types should, therefore, be readdressed in case-control studies on the basis of
      serology, which can reveal viral activities over years. The viruses lingering in
      all people are apparently activated by sunlight (UV) exposure, by
      immunosuppression, and by hyperproliferation of the epithelium (psoriasis) and/or
      in the specific genetic background of the host (EV). It is intriguing that most
      of these factors are established risk factors in skin carcinogenesis. The weak
      transforming activity of cutaneous HPV in vitro compared with the transforming
      activity of genital HPV may explain the need for activators and synergistic
      factors. The antiapoptotic activities of E6 proteins of cutaneous HPV could be
      relevant to oncogenesis in the interplay with UV exposure. Prospective studies
      should determine the kinetics of HPV activation relative to tumor development.

PMID- 12807947
TI  - Chapter 9: Role of mucosal human papillomavirus in nongenital cancers.
AB  - Established associations between human papillomavirus (HPV) and lower genital
      tract cancers provide a framework from which to evaluate a possible pathogenic
      role for the virus in cancers at nongenital sites. Proposed associations must fit
      coherently within the context of our current knowledge of the epidemiology and
      biology of HPV. In this article, insights obtained from studies of the etiologic
      link between mucosal-type HPV infection and four specific human cancers are
      described briefly. Specific characteristics, shared among cancers caused by HPV,
      are then used by extrapolation to discuss possible associations between certain
      other nongenital cancers and mucosal HPV infections in a manner intended to
      supplement, and in no way to supplant, the classic Hill criteria for causal
      inference.

PMID- 12807948
TI  - Chapter 10: Cervical cancer screening using visualization techniques.
AB  - There is a resurgence of interest in the use of visual techniques to identify
      cervical intraepithelial neoplasia (CIN). These visual techniques can be divided
      into two general categories. One is the simple visual screening method, such as
      direct visual inspection (DVI), during which the cervix is visualized with either
      the naked eye or a low-power magnification device after the application of a
      solution of 3% to 5% acetic acid that is used as a chemical contrast agent to
      highlight regions of CIN. DVI has been evaluated in a number of large clinical
      trials and is considered by some to be a possible alternative to cervical
      cytology for primary cervical cancer screening in low-resource settings. The
      advantages of DVI compared with cervical cytology for these settings are that it
      is inexpensive, it does not require a laboratory infrastructure, and it provides
      an immediate result, allowing the use of "screen and treat" protocols. The major
      disadvantage of DVI is that it is relatively nonspecific and that its sensitivity
      is low compared with testing for human papillomavirus. The other category of
      visual techniques includes devices that use electro-optical sensors and light of
      specific wavelengths produced by lasers or specialized light sources to identify
      and localize regions of CIN on the cervix. Although these "high-technology"
      devices are not yet in routine clinical use, several groups and companies have
      such devices in clinical trials.

PMID- 12807949
TI  - Chapter 11: Future directions in cervical pathology.
AB  - Technologic innovations, including the development of improved sampling devices,
      liquid-based collection systems, and computer-assisted screening, have
      revolutionized cervical cytology. Biologic discoveries in upcoming years promise
      to transform our understanding of the pathogenesis of cervical neoplasia, leading
      to another quantum leap in our approach to screening and prevention. This review
      summarizes the opportunities and challenges that recent and anticipated advances
      in pathology present for epidemiologic research.

PMID- 12807950
TI  - Chapter 12: Human papillomavirus technologies.
AB  - Currently, human papillomavirus (HPV) DNA tests validated in large trials and
      epidemiological studies are the hybrid capture second-generation (HC2) HPV DNA
      assay and a variety of polymerase chain reaction (PCR) protocols employing
      degenerate or consensus primers. This article describes the currently available
      technology for HPV detection and discusses novel technologies and their potential
      for large-scale screening. Ideally, an HPV test should allow detection of
      multiple HPV types, identify individual types, and provide quantitative
      information about the viral load of each individual type found. Moreover, it
      should be easy to perform, be highly reproducible, with a high specificity and
      sensitivity, and amenable for high throughput analysis and automation. Because we
      do not yet fully understand the true value of viral load and the biological
      relevance of the different HPV types, any HPV test should be able to detect the
      clinically relevant high-risk types with a sufficient sensitivity of at least 10
      000 genome copies per sample. To validate the different current and future test
      systems and to compare inter-laboratory performance we urgently need reference
      samples, validated reagents, and standardized protocols.

PMID- 12807951
TI  - Chapter 13: Primary screening of cervical cancer with human papillomavirus tests.
AB  - Despite its history of success in cancer screening, Pap cytology has important
      limitations, particularly its high false-negative rate, which carries important
      public health implications. Since the mid-1990s, there has been substantial
      interest in the use of human papillomavirus (HPV) DNA testing in cervical cancer
      screening under the premise that the testing of cervical cells for the causative
      agent of cervical cancer could have acceptable screening performance, while being
      more reproducible in clinical practice than Pap cytology. There have been several
      studies assessing the utility of HPV testing compared with the Pap test as a
      screening tool. These studies varied widely in lesion-outcome definition and in
      methodology. No studies were based on cervical cancer incidence or mortality. No
      randomized controlled trials have yet been published; all of the studies were
      based on concomitant testing for HPV and cytology or additional tests. HPV
      testing has greater sensitivity (average, 27%) but somewhat lower specificity
      (average, 8%) than Pap cytology for detecting high-grade lesions. Screening of
      women aged 30 years or older tends to improve test specificity, but it also does
      so for cytology. The combination of cytology and HPV attained high-negative
      predictive values, which suggests that their joint use could allow screening
      intervals to be safely increased, thus lowering costs. Although evidence is yet
      to come from long-term studies and from randomized controlled trials with high
      grade lesions and invasive cancer as outcomes, HPV testing is clearly one of the
      most promising new technologies and has the potential to improve cervical cancer
      screening effectiveness in many settings.

PMID- 12807952
TI  - Chapter 14: Role of triage testing in cervical cancer screening.
AB  - The classic model of cervical cancer prevention-primary screening with cytology,
      followed by diagnostic colposcopically directed biopsy, and finally treatment of
      cancer precursors-is undergoing dynamic change. The introduction of human
      papillomavirus (HPV) DNA testing and other new modalities provides more options
      but increases complexity in the sequence of screening, triage, diagnosis, and
      patient management. This chapter will focus on the role of triage and risk
      stratification in management. The utility of HPV testing has been established for
      triage of cytologic findings of atypical squamous cells of undetermined
      significance but not for low-grade squamous intraepithelial lesions or worse.
      Countries without established cytology services may consider alternative
      screening, triage, and treatment programs that may be more readily implemented
      than a resource-rich "cytology followed by colposcopy" paradigm requiring an
      infrastructure of highly trained personnel. The diagnostic step of colposcopy and
      directed biopsy is not completely sensitive in the detection of cervical
      intraepithelial neoplasia (CIN) 2 or 3 as is sometimes assumed. The partial
      insensitivity of this diagnostic step results in a population of women with
      negative colposcopically directed-biopsy findings but at increased risk for
      missed prevalent disease: these women may require additional triage rather than
      resumption of routine screening. As more efficient screening, triage, and
      diagnosis increase the sensitivity of detection of even very small CIN2 or CIN3,
      overtreatment of lesions that might otherwise regress becomes a concern and
      highlights the need to identify accurate markers of risk of progression to
      cancer. Markers of molecular events further along the pathway from HPV infection
      to development of cancer may ultimately provide more specificity in triage and
      diagnosis.

PMID- 12807953
TI  - Chapter 15: Public health policy and cost-effectiveness analysis.
AB  - Recent scientific advances are providing an opportunity to revisit strategies for
      cervical cancer prevention. How to invest health resources wisely, such that
      public health benefits are maximized-and opportunity costs are minimized-is a
      critical question in the setting of enhanced cytologic screening methods, human
      papillomavirus DNA testing, and vaccine development. Developing sound clinical
      guidelines and public health policy will require careful consideration of the
      incremental benefits, harms, and costs associated with new interventions compared
      with existing interventions, at both an individual and a population level. In
      addition to an intervention's effectiveness, public health decision making
      requires the consideration of its feasibility, sustainability, and affordability.
      No clinical trial or single cohort study will be able to simultaneously consider
      all of these components. Cost-effectiveness analysis and disease-simulation
      modeling, capitalizing on data from multiple sources, can serve as a valuable
      tool to extend the time horizon of clinical trials, to evaluate more strategies
      than possible in a single clinical trial, and to assess the relative costs and
      benefits of alternative policies to reduce mortality from cervical cancer.

PMID- 12807954
TI  - Chapter 16: Prophylactic human papillomavirus vaccines.
AB  - Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles
      (VLPs) are currently in human clinical trials. The main long-term goal of the
      vaccine is to reduce the incidence of cervical cancer and its precursors. In
      animal papillomavirus models, systemic immunization with L1 VLPs can induce high
      titers of neutralizing antibodies that confer protection against high-dose
      experimental papillomavirus challenge. In humans, systemic vaccination with L1
      VLPs has been well tolerated and induced high serum antibody titers (at least 40
      times higher than titers seen following natural infection). A recent proof of
      principle HPV16 L1 VLP efficacy trial has shown excellent protection against
      persistent HPV16 infection and associated cytological abnormalities. Large scale
      efficacy trials of L1 VLPs from HPV16 and 18 (the HPV types found most frequently
      in cervical cancer), with or without HPV6 and 11 (the HPV types responsible for
      most genital warts), are planned. If the results of these large trials support
      the encouraging results of the early trials, they should lead to a commercial
      prophylactic HPV vaccine. Implementation issues may include how to make the
      vaccine available in the developing world, where the majority of cervical cancer
      cases occur, the appropriate age of vaccination, and the role of male
      vaccination. Because a VLP vaccine is likely to provide type-specific protection,
      increasing the number of cancer-associated HPV types in the vaccine is a likely
      approach to broadening the protection to additional types. There will probably
      also be efforts to develop alternative vaccine formulations better suited to
      implementation in developing countries as well as attempts to develop vaccines
      with a therapeutic activity against established HPV infection because a combined
      prophylactic/therapeutic vaccine may be expected to have an even greater impact
      than a purely prophylactic vaccine on HPV induced disease.

PMID- 12807955
TI  - Chapter 17: Genital human papillomavirus infections--current and prospective
      therapies.
AB  - Many therapies are available for the treatment of human papillomavirus (HPV)
      associated disease, particularly external genital warts. However, at present,
      these therapies aim to remove the lesion rather than specifically target HPV
      infection. When disease and infection are local, as in cervical intraepithelial
      neoplasia (CIN), excisional therapies removing lesion and transformation
      susceptible cells are highly effective. However, when infection is regional, as
      is usually the case for the anogenital warts, vulval intraepithelial neoplasia
      (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia,
      and vaginal intraepithelial neoplasia, then current treatments are generally
      inadequate, with high recurrence rates. Future therapies will be directly or
      indirectly antiviral, targeting HPV protein functions or enhancing the ability of
      the immune system to resolve infection or inducing apoptosis indirectly in HPV
      infected cells. In the short to the medium term, immunotherapies for low-grade
      disease are the most likely to be in the clinic. Vaccines targeting the E1 and E2
      early proteins combined with immunomodulators or conventional adjuvants that
      induce a strong cell-mediated HPV antigen-specific response and good immune
      memory would be the predicted combination. Vaccines designed to target high-grade
      intraepithelial disease, even when used in combination with immunomodulators, are
      unlikely to effect lesion clearance in more than a fraction of the cases.
      However, they may have a role as adjunct therapy after cervical conization to
      prevent the recurrence of CIN or HPV reinfection. They certainly appear to have a
      role in multifocal disease, such as VIN and AIN, where partial clearance may be
      effected and lesion size reduced enough for effective ablative or excisional
      therapy. It seems unlikely that anti-HPV chemotherapies specifically targeting
      HPV protein functions will be in the clinic in the medium term. However, agents
      such as indole-3-carbinol have shown efficacy in small clinical trials, and if
      these effects are confirmed in larger, randomized, placebo-controlled trials,
      they could be clinically useful.

PMID- 12807956
TI  - Chapter 18: Statistical issues in the design and analysis of studies of human
      papillomavirus and cervical neoplasia.
AB  - Appropriately sophisticated statistical approaches are crucial for addressing the
      increasingly complex set of critical questions that follow from the recognition
      that human papillomavirus (HPV) is a necessary causal factor for cervical cancer.
      Cervical cancer researchers have defined the major stages of cervical
      carcinogenesis, with HPV infection as the necessary cause. Focus of etiologic
      studies is shifting from establishing causality to determining risk factors for
      HPV persistence and neoplastic progression using serially collected biomarkers.
      Prevention-oriented epidemiology and trials of new screening strategies and
      vaccines will rely on surrogate endpoints because we cannot let women develop
      cancer when it can be prevented. Future epidemiologic and prevention studies of
      HPV infection and cervical carcinogenesis will exploit subtle pathologic
      distinctions and will employ improved measurements of complex molecular biologic
      phenomena. The anticipated statistical issues are highlighted in this discussion.

PMID- 12807958
TI  - Telomeres: a diagnosis at the end of the chromosomes.
AB  - In recent years, subtelomeric rearrangements have been identified as a major
      cause of mental retardation and/or malformation syndromes. So far, over 2500
      subjects with mental retardation have been tested and reported of whom
      approximately 5% appeared to have a subtelomeric rearrangement. In this review,
      the clinical aspects of each known (submicroscopic) subtelomeric deletion will be
      presented and the various methods available for detecting subtelomeric
      abnormalities will be discussed. Not only will the patients and their families
      benefit from a good collection and report of the various telomeric abnormalities
      and their clinical phenotype, but it will also give more insight into the
      aetiology of mental retardation and malformation syndromes.

PMID- 12807959
TI  - Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate.
AB  - MSX1 has been proposed as a gene in which mutations may contribute to non
      syndromic forms of cleft lip and/or cleft palate. Support for this comes from
      human linkage and linkage disequilibrium studies, chromosomal deletions resulting
      in haploinsufficiency, a large family with a stop codon mutation that includes
      clefting as a phenotype, and the Msx1 phenotype in a knockout mouse. This report
      describes a population based scan for mutations encompassing the sense and
      antisense transcribed sequence of MSX1 (two exons, one intron). We compare the
      completed genomic sequence of MSX1 to the mouse Msx1 sequence to identify non
      coding homology regions, and sequence highly conserved elements. The samples
      studied were drawn from a panethnic collection including people of European,
      Asian, and native South American ancestry. The gene was sequenced in 917 people
      and potentially aetiological mutations were identified in 16. These included
      missense mutations in conserved amino acids and point mutations in conserved
      regions not identified in any of 500 controls sequenced. Five different missense
      mutations in seven unrelated subjects with clefting are described. Evolutionary
      sequence comparisons of all known Msx1 orthologues placed the amino acid
      substitutions in context. Four rare mutations were found in non-coding regions
      that are highly conserved and disrupt probable regulatory regions. In addition, a
      panel of 18 population specific polymorphic variants were identified that will be
      useful in future haplotype analyses of MSX1. MSX1 mutations are found in 2% of
      cases of clefting and should be considered for genetic counselling implications,
      particularly in those families in which autosomal dominant inheritance patterns
      or dental anomalies appear to be cosegregating with the clefting phenotype.

PMID- 12807961
TI  - Gene expression signatures identify novel regulatory pathways during murine lung
      development: implications for lung tumorigenesis.
AB  - Oligonucleotide array based analysis was conducted to examine the temporal
      pattern of gene expression across the various stages of lung development to
      identify regulatory pathways at key developmental time points. Whole embryo total
      RNA or embryonic lung total RNA was harvested from A/J mice at seven
      developmental stages. To investigate changes in gene expression during lung
      development, four samples from each stage were examined using Affymetrix U74Av2
      murine oligonucleotide microarrays. From the over 12,000 genes and ESTs
      represented on the array, 1346 genes and ESTs were identified as having a
      significant change in expression between at least one time point and the others
      (p<0.001, Kruskal-Wallis test). Within this group of approximately 1300 genes,
      four patterns of expression were seen: (1) upregulation during the embryonic
      period of development (up-down); (2) upregulation during the postnatal period of
      lung development (down-up) and (3) fluctuating expression, up initially, down for
      one or more time points, and then up again (up-down-up); and (4) vice versa (down
      up-down). Expression patterns of genes previously reported to be involved in
      pulmonary development were also examined. Using the pathway visualisation tool,
      GenMapp, at least three regulatory pathways were found to contain clusters of
      differentially expressed genes: Wnt signalling, cell cycle, and apoptosis.
      Furthermore, we have shown that many of the genes involved in lung development
      are either known oncogenes or tumour suppressor genes altered in lung cancer,
      such as Cyr61, Rassf1a, and Dutt1/Robo1, or putative lung cancer genes. In
      addition, the genes identified pertinent to early development may also serve as
      candidate susceptibility genes for various inherited lung cancer disorders as
      well as for various heritable disorders of lung development. These results will
      contribute to our understanding of novel aspects of the regulatory machinery for
      embryonic lung development and of the genes involved in lung tumorigenesis.

PMID- 12807962
TI  - A new genetic locus for X linked progressive cone-rod dystrophy.
AB  - X linked progressive cone-rod dystrophy (COD) is a retinal disease primarily
      affecting the cone photoreceptors. The disease is genetically heterogeneous and
      two loci, COD1 (Xp21.1-11.4) and COD2 (Xq27.2-28), have been previously
      identified. COD1 was recently shown to be caused by mutations in RPGR exon ORF15
      (Xp21.1), the gene that is also responsible for RP3 type retinitis pigmentosa. In
      this study, we performed a linkage study to map the disease gene in a large
      Finnish family with X linked cone-rod dystrophy, using a panel of 39 X
      chromosomal markers. Several recombinations between the disease gene and markers
      in the Xp21.1-p11.4 region have excluded COD1 as a candidate locus in this
      family. Consistent with the linkage results, no mutation was detected by direct
      PCR sequencing of the coding region of RPGR, including exon ORF15. The COD2 locus
      has been also excluded as the site of the gene on the basis of negative lod score
      values obtained for COD2 linked markers. The disease causing gene of the studied
      COD family has been localised between the markers DXS10042 and DXS8060 on Xp11.4
      q13.1. Positive pairwise lod scores >3 were obtained for markers DXS993, MAOB,
      DXS1055, and DXS1194. Since this locus is distinct from the previously identified
      two loci, COD1 and COD2, our results establish a new third genetic locus for X
      linked progressive cone-rod dystrophy and further expands our knowledge about the
      genetic heterogeneity underlying this disease entity.

PMID- 12807964
TI  - A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.
AB  - Asphyxiating thoracic dystrophy (ATD), or Jeune syndrome, is a multisystem
      autosomal recessive disorder associated with a characteristic skeletal dysplasia
      and variable renal, hepatic, pancreatic, and retinal abnormalities. We have
      performed a genome wide linkage search using autozygosity mapping in a cohort of
      four consanguineous families with ATD, three of which originate from Pakistan,
      and one from southern Italy. In these families, as well as in a fifth
      consanguineous family from France, we localised a novel ATD locus (ATD) to
      chromosome 15q13, with a maximum cumulative two point lod score at D15S1031
      (Zmax=3.77 at theta=0.00). Five consanguineous families shared a 1.2 cM region of
      homozygosity between D15S165 and D15S1010. Investigation of a further four
      European kindreds, with no known parental consanguinity, showed evidence of
      marker homozygosity across a similar interval. Families with both mild and severe
      forms of ATD mapped to 15q13, but mutation analysis of two candidate genes,
      GREMLIN and FORMIN, did not show pathogenic mutations.

PMID- 12807963
TI  - Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene
      with Alzheimer's disease.
AB  - Although possession of the epsilon 4 allele of the apolipoprotein E gene appears
      to be an important biological marker for Alzheimer's disease (AD) susceptibility,
      strong evidence indicates that at least one additional risk gene exists on
      chromosome 12. Here, we describe an association of the 3'-UTR +1073 C/T
      polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in
      French sporadic (589 cases and 663 controls) and American familial (230 affected
      sibs and 143 unaffected sibs) populations. The age and sex adjusted odds ratio
      between the CC+CT genotypes versus the TT genotypes was 1.56 (p=0.001) in the
      French sample and 1.92 (p=0.02) in the American sample. Furthermore, we have
      discovered a new T/A polymorphism two bases upstream of the +1073 C/T
      polymorphism. This +1071 T/A polymorphism was not associated with the disease,
      although it may weakly modulate the impact of the +1073 C/T polymorphism. Using
      3'-UTR sequence probes, we have observed specific DNA protein binding with
      nuclear proteins from lymphocyte, astrocytoma, and neuroblastoma cell lines, but
      not from the microglia cell line. This binding was modified by both the +1071 T/A
      and +1073 C/T polymorphisms. In addition, a trend was observed between the
      presence or absence of the +1073 C allele and the level of astrocytic activation
      in the brain of AD cases. However, Abeta(40), Abeta(42), Abeta total, and Tau
      loads or the level of microglial cell activation were not modulated by the 3'-UTR
      OLR1 polymorphisms. Finally, we assessed the impact of these polymorphisms on the
      level of OLR1 expression in lymphocytes from AD cases compared with controls. The
      OLR1 expression was significantly lower in AD cases bearing the CC and CT
      genotypes compared with controls with the same genotypes. In conclusion, our data
      suggest that genetic variation in the OLR1 gene may modify the risk of AD.

PMID- 12807965
TI  - Spectrum of NSD1 mutations in Sotos and Weaver syndromes.
AB  - Sotos syndrome is an overgrowth syndrome characterised by pre- and postnatal
      overgrowth, macrocephaly, advanced bone age, and typical facial features. Weaver
      syndrome is a closely related condition characterised by a distinctive
      craniofacial appearance, advanced carpal maturation, widened distal long bones,
      and camptodactyly. Haploinsufficiency of the NSD1 gene has recently been reported
      as the major cause of Sotos syndrome while point mutations accounted for a
      minority of cases. We looked for NSD1 deletions or mutations in 39 patients with
      childhood overgrowth. The series included typical Sotos patients (23/39), Sotos
      like patients (lacking one major criteria, 10/39), and Weaver patients (6/39). We
      identified NSD1 deletions (6/33) and intragenic mutations (16/33) in Sotos
      syndrome patients. We also identified NSD1 intragenic mutations in 3/6 Weaver
      patients. We conclude therefore that NSD1 mutations account for most cases of
      Sotos syndrome and a significant number of Weaver syndrome cases in our series.
      Interestingly, mental retardation was consistently more severe in patients with
      NSD1 deletions. Macrocephaly and facial gestalt but not overgrowth and advanced
      bone age were consistently observed in Sotos syndrome patients. We suggest
      therefore considering macrocephaly and facial gestalt as mandatory criteria for
      the diagnosis of Sotos syndrome and overgrowth and advanced bone age as minor
      criteria.

PMID- 12807966
TI  - Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar
      hypoplasia.

PMID- 12807967
TI  - Haplotype analysis of distantly related populations implicates corneodesmosin in
      psoriasis susceptibility.

PMID- 12807968
TI  - Association of genetic variants in the HDL receptor, SR-B1, with abnormal lipids
      in women with coronary artery disease.

PMID- 12807969
TI  - Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease
      transmission to offspring.

PMID- 12807970
TI  - Linkage and linkage disequilibrium searched for between non-syndromic cleft
      palate and four candidate loci.

PMID- 12807971
TI  - Is the locus for Costello syndrome on 11p?

PMID- 12807973
TI  - Is growth hormone treatment beneficial or harmful in Costello syndrome?

PMID- 12807974
TI  - Hereditary phaeochromocytomas and paragangliomas: a study of five susceptibility
      genes.

PMID- 12807975
TI  - Modulation of methylation in the FMR1 promoter region after long term treatment
      with L-carnitine and acetyl-L-carnitine.

PMID- 12807976
TI  - Laugier-Hunziker syndrome: an important differential diagnosis for Peutz-Jeghers
      syndrome.

PMID- 12807977
TI  - Microcephaly-cardiomyopathy syndrome: expansion of the phenotype.

PMID- 12807978
TI  - A unique form of hypodontia seen in Vietnamese patients: clinical and molecular
      analysis.

PMID- 12807979
TI  - Genetic information but not termination: pregnant women's attitudes and
      willingness to pay for carrier screening for deafness genes.

PMID- 12807980
TI  - Possible founder effect of rapsyn N88K mutation and identification of novel
      rapsyn mutations in congenital myasthenic syndromes.

PMID- 12807981
TI  - Recurrent mutations in the NF1 gene are common among neurofibromatosis type 1
      patients.

PMID- 12807982
TI  - GABA: exciting again in its own right.

PMID- 12807983
TI  - EEG oscillations at 600 Hz are macroscopic markers for cortical spike bursts.
AB  - The human electroencephalogram (EEG) is generated predominantly by synchronised
      cortical excitatory postsynaptic potentials oscillating at frequencies <100 Hz.
      Unusually, EEG responses to electrical nerve stimulation contain brief bursts of
      high-frequency (600 Hz) wavelets. Here we show, in awake monkeys, that a subset
      of primary somatosensory cortex single units consistently fires both bursts and
      single spikes phase-locked to EEG wavelets. Spike bursts were also evoked by
      tactile stimuli, proving that this is a natural response mode. EEG wavelets at
      600 Hz may therefore permit non-invasive assessment of population spike timing in
      human cortex.

PMID- 12807984
TI  - Cellular and network mechanisms underlying spontaneous sharp wave-ripple
      complexes in mouse hippocampal slices.
AB  - The mammalian hippocampus displays a peculiar pattern of fast (approximately 200
      Hz) network oscillations superimposed on slower sharp waves. Such sharp wave
      ripple complexes (SPW-R) have been implicated in memory consolidation. We have
      recently described a novel and unique method for studying SPW-R in naive slices
      of murine hippocampus. Here, we used this model to analyse network and cellular
      mechanisms of this type of network activity. SPW-R are usually generated within
      area CA3 but can also originate within the isolated CA1 region. Cellular
      synchronisation during SPW-R requires both excitatory and inhibitory synaptic
      transmission as well as electrical coupling, the latter being particularly
      important for the high-frequency component. Extracellular and intracellular
      recordings revealed a surprisingly strong inhibition of most CA1 pyramidal cells
      during SPW-R. A minority of active cells, however, increases action potential
      frequency and fires in strict synchrony with the field ripples. This strong
      separation between members and non-members of the network may serve to ensure a
      high signal-to-noise ratio in information processing during sharp wave-ripple
      complexes.

PMID- 12807987
TI  - T- and L-type Ca2+ currents in freshly dispersed smooth muscle cells from the
      human proximal urethra.
AB  - The purpose of the present study was to characterise Ca2+ currents in smooth
      muscle cells isolated from biopsy samples taken from the proximal urethra of
      patients undergoing surgery for bladder or prostate cancer. Cells were studied at
      37 degrees C using the amphotericin B perforated-patch configuration of the patch
      clamp technique. Currents were recorded using Cs+-rich pipette solutions to block
      K+ currents. Two components of current, with electrophysiological and
      pharmacological properties typical of T- and L-type Ca2+ currents, were present
      in these cells. When steady-state inactivation curves for the L current were
      fitted with a Boltzmann equation, this yielded a V1/2 of -45+/-5 mV. In contrast,
      the T current inactivated with a V1/2 of -80+/-3 mV. The L currents were reduced
      in a concentration-dependent manner by nifedipine (ED50=159+/-54 nM) and Ni2+
      (ED50=65+/-16 microM) but were enhanced when external Ca2+ was substituted with
      Ba2+. The T current was little affected by TTX, reduction in external Na+,
      application of nifedipine at concentrations below 300 nM or substitution of
      external Ca2+ with Ba2+, but was reduced by Ni2+ with an ED50 of 6+/-1 microM.
      When cells were stepped from -100 to -30 mV in Ca2+-free conditions, small inward
      currents could be detected. These were enhanced 40-fold in divalent-cation-free
      solution and blocked in a concentration-dependent manner by Mg2+ with an ED50 of
      32+/-16 microM. These data support the idea that human urethral myocytes possess
      currents with electrophysiological and pharmacological properties typical of T-
      and L-type Ca2+ currents.

PMID- 12807986
TI  - C terminus L-type Ca2+ channel calmodulin-binding domains are 'auto-agonist'
      ligands in rabbit ventricular myocytes.
AB  - L-type Ca2+ channel C terminus calmodulin (CaM)-binding domains are molecular
      determinants for Ca(2+)-CaM-dependent increases in L-type Ca2+ current (ICa), and
      a CaM-binding IQ domain mimetic peptide (IQmp) increases L-type Ca2+ channel
      current by promoting a gating mode with prolonged openings (mode 2), suggesting
      the intriguing possibility that CaM-binding domains are 'auto-agonist' signalling
      molecules. In order to test the breadth of this concept, we studied the effect of
      a second C terminus CaM-binding domain (CB) mp (CBmp), in conjunction with IQmp,
      on single L-type Ca2+ channel currents in excised cell membrane patches from
      rabbit ventricular myocytes. Here we show that both CBmp and IQmp are agonist
      ligands that non-additively increase L-type Ca2+ channel opening probability (Po)
      by inducing mode 2 gating. CBmp and IQmp agonist effects were lost under
      conditions favouring calcification of CaM (Ca(2+)-CaM, 150 nM free Ca2+ and 10-20
      microM CaM), but persisted in the presence of CaM (0-20 microM) under conditions
      adverse to Ca(2+)-CaM (20 mM BAPTA), indicating that CaM-binding domains increase
      L-type Ca2+ channel Po by a low Ca(2+)-CaM activity mechanism. Increasing Ca(2+)
      CaM in the bath (cytosol) reduced the efficacy of CBmp and IQmp signals with Ba2+
      as charge carrier, suggesting that CaM binding motifs target a site outside of
      the pore region. We measured the combined effects of CBmp and Ca(2+)-CaM
      dependent protein kinase II (CaMKII) on L-type Ca2+ channels by using an
      engineered Ca(2+)-CaM-independent form of CaMKII that remains active under low
      Ca(2+)-CaM conditions, permissive for CBmp signalling. CBmp and CaMKII increased
      L-type Ca2+ channel Po in a non-additive manner, suggesting that low and high
      Ca(2+)-CaM-dependent L-type Ca2+ channel facilitation pathways converge upon a
      common signalling mechanism.

PMID- 12807988
TI  - Resting membrane potential regulates Na(+)-Ca2+ exchange-mediated Ca2+ overload
      during hypoxia-reoxygenation in rat ventricular myocytes.
AB  - In the heart, reperfusion following an ischaemic episode can result in a marked
      increase in [Ca2+]i and cause myocyte dysfunction and death. Although the Na(+)
      Ca2+ exchanger has been implicated in this response, the ionic mechanisms that
      are responsible have not been identified. In this study, the hypothesis that the
      diastolic membrane potential can influence Na(+)-Ca2+ exchange and Ca2+
      homeostasis during chemically induced hypoxia-reoxygenation has been tested using
      right ventricular myocytes isolated from adult rat hearts. Superfusion with
      selected [K+]o of 0.5, 2.5, 5, 7, 10 and 15 mM yielded the following resting
      membrane potentials: -27.6+/-1.63 mV, -102.2+/-1.89, -86.5+/-1.03, -80.1+/-1.25, 
      73.6+/-1.02 and -66.4+/-1.03, respectively. In a second set of experiments
      myocytes were subjected to chemically induced hypoxia-reoxygenation at these
      different [K+]o, while [Ca2+]i was monitored using fura-2. These results
      demonstrated that after chemically induced hypoxia-reoxygenation had caused a
      marked increase in [Ca2+]i, hyperpolarization of myocytes with 2.5 mM [K+]o
      significantly reduced [Ca2+]i (7.5+/-0.32 vs. 16.9+/-0.55%); while depolarization
      (with either 0.5 or 15 mM [K+]o) significantly increased [Ca2+]i (31.8+/-3.21 and
      20.8+/-0.36 vs. 16.9+/-0.55%, respectively). As expected, at depolarized membrane
      potentials myocyte hypercontracture and death increased in parallel with Ca2+
      overload. The involvement of the Na(+)-Ca2+ exchanger in Ca2+ homeostasis was
      evaluated using the Na(+)-Ca2+ exchanger inhibitor KB-R7943. During reoxygenation
      KB-R7943 (5 microM) almost completely prevented the increase in [Ca2+]i both in
      control conditions (in 5 mM [K+]o: 2.2+/-0.40 vs. 10.8+/-0.14%) and in
      depolarized myocytes (in 15 mM [K+]o: -2.1+/-0.51 vs. 11.3+/-0.05%). These
      findings demonstrate that the resting membrane potential of ventricular myocytes
      is a critical determinant of [Ca2+]i during hypoxia-reoxygenation. This appears
      to be due mainly to an effect of diastolic membrane potential on the Na(+)-Ca2+
      exchanger, since at depolarized potentials this exchanger mechanism operates in
      the reverse mode, causing a significant Ca2+ influx.

PMID- 12807989
TI  - Differential modulation of intracortical inhibition in human motor cortex during
      selective activation of an intrinsic hand muscle.
AB  - Paired-pulse transcranial magnetic stimulation (TMS) was used to assess the
      effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons
      controlling three intrinsic hand muscles in humans. We hypothesised that the
      suppression of ICI with selective activation of a muscle would be restricted to
      corticospinal neurons controlling the muscle targeted for activation. Surface EMG
      was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI)
      and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested
      at rest and during weak selective activation of APB or ADM, while they attempted
      to keep the other muscles relaxed using visual feedback. Paired-pulse TMS was
      applied with a circular coil oriented to produce antero-posterior (AP) current
      flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal
      neurons) and with postero-anterior (PA) currents (to preferentially evoke I1
      waves). Paired-pulse TMS was less effective in suppressing the muscle evoked
      potential (MEP) when the muscle was targeted for selective activation, with both
      AP and PA stimulation. The mechanism for this includes effects on late I waves,
      as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves
      in corticospinal neurons. ICI circuits activated by TMS, which exert their
      effects on late I waves but do not affect I1 waves, are strongly implicated in
      this modulation. With AP stimulation, paired-pulse inhibition was not
      significantly altered for corticospinal neurons controlling other muscles of the
      same hand which were required to be inactive during the selective activation
      task. This differential modulation was not seen with PA stimulation, which
      preferentially activates I1 waves and evokes a MEP that is less influenced by
      ICI. The observations with AP stimulation suggest that selective activation of a
      hand muscle is accompanied by a selective suppression of ICI effects on the
      corticospinal neurons controlling that muscle. The pattern of differential
      modulation of ICI effectiveness with voluntary activation suggests that the ICI
      circuits assist the corticospinal system in producing fractionated activity of
      intrinsic hand muscles.

PMID- 12807990
TI  - GABA depolarizes neuronal progenitors of the postnatal subventricular zone via
      GABAA receptor activation.
AB  - Previous studies have reported the presence of migrating and dividing neuronal
      progenitors in the subventricular zone (SVZ) and rostral migratory stream (RMS)
      of the postnatal mammalian brain. Although the behaviour of these progenitors is
      thought to be influenced by local signals, the nature and mode of action of the
      local signals are largely unknown. One of the signalling molecules known to
      affect the behaviour of embryonic neurons is the neurotransmitter GABA. In order
      to determine whether GABA affects neuronal progenitors via the activation of
      specific receptors, we performed cell-attached, whole-cell and gramicidin
      perforated patch-clamp recordings of progenitors in postnatal mouse brain slices
      containing either the SVZ or the RMS. Recorded cells displayed a morphology
      typical of migrating neuronal progenitors had depolarized zero-current resting
      potentials, and lacked action potentials. A subset of progenitors contained GABA
      and stained positive for glutamic acid decarboxylase 67 (GAD-67) as shown by
      immunohistochemistry. In addition, every neuronal progenitor responded to GABA
      via picrotoxin-sensitive GABAA receptor (GABAAR) activation. GABAARs displayed an
      ATP-dependent rundown and a low sensitivity to Zn2+. GABA responses were
      sensitive to benzodiazepine agonists, an inverse agonist, as well as a
      barbiturate agonist. While GABA was hyperpolarizing at the zero-current resting
      potentials, it was depolarizing at the cell resting potentials estimated from the
      reversal potential of K+ currents through a cell-attached patch. Thus, our study
      demonstrates that neuronal progenitors of the SVZ/RMS contain GABA and are
      depolarized by GABA, which may constitute the basis for a paracrine signal among
      neuronal progenitors to dynamically regulate their proliferation and/or
      migration.

PMID- 12807992
TI  - Exercise in hypoxic environments: the mechanism remains elusive.

PMID- 12807991
TI  - Properties and modulation of the G protein-coupled K+ channel in rat cerebellar
      granule neurons: ATP versus phosphatidylinositol 4,5-bisphosphate.
AB  - Cerebellar granule (CG) neurons express a G protein-gated K+ current (GIRK) that
      is involved in the neurotransmitter regulation of the excitatory input to the
      Purkinje fibres of the cerebellum. Here, we characterized the single-channel
      behaviour of GIRK in CG neurons, and examined the effects of several known
      modulators of GIRK and their putative physiological roles. Whole-cell GIRKs were
      activated by baclofen, a GABAB receptor agonist. In cell-attached patches,
      baclofen activated GIRK with a single-channel conductance of 34 pS and a mean
      open time of 0.5 ms. In inside-out patches, application of GTPgammaS to the
      cytoplasmic side activated GIRK with similar kinetic properties. Addition of 2 mM
      ATP resulted in a marked increase in GIRK activity and induced longer-lived
      openings with a mean open time of 2.3 ms (ATP-dependent gating). Brain cytosolic
      fraction or free fatty acids inhibited this effect of ATP, and this was reversed
      by addition of purified recombinant brain fatty acid binding protein. Applying
      phosphatidylinositol 4,5-bisphosphate (PIP2) to inside-out patches in place of
      ATP also increased GIRK activity; however, only an increase in the frequency of
      opening was observed. The stimulatory effect of PIP2 on GIRK activity was not
      inhibited by the cytosolic fraction. Following maximal activation by PIP2, ATP
      caused an additional 2.2-fold increase in GIRK activity. These results show that
      GIRKs in CG neurons are regulated by positive and negative modulators that affect
      frequency as well as open time duration. The net effect is that the ligand
      activated GIRK is in the 'low activity' state associated with short-lived
      openings, mainly due to strong action of the cytosolic inhibitor of ATP-dependent
      gating. Our results also show that intracellular ATP modulates GIRK via pathways
      different from that of PIP2 in CG neurons.

PMID- 12807993
TI  - Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea
      pig enteric nervous system.
AB  - Electrophysiological recording was used to study a type of slow excitatory
      postsynaptic potential (slow EPSP) that was mediated by release of ATP and its
      action at P2Y1 receptors on morphologically identified neurones in the submucosal
      plexus of guinea-pig small intestine. MRS2179, a selective P2Y1 purinergic
      receptor antagonist, blocked both the slow EPSP and mimicry of the EPSP by
      exogenously applied ATP. Increased conductance accounted for the depolarization
      phase of the EPSP, which occurred exclusively in neurones with S-type
      electrophysiological behaviour and uniaxonal morphology. The purinergic
      excitatory input to the submucosal neurones came from neighbouring neurones in
      the same plexus, from neurones in the myenteric plexus and from sympathetic
      postganglionic neurones. ATP-mediated EPSPs occurred coincident with fast
      nicotinic synaptic potentials evoked by the myenteric projections and with
      noradrenergic IPSPs evoked by sympathetic fibres that innervated the same
      neurones. The P2Y1 receptor on the neurones was identified as a metabotropic
      receptor linked to activation of phospholipase C, synthesis of inositol 1,4,5
      trisphosphate and mobilization of Ca2+ from intracellular stores.

PMID- 12807994
TI  - Systemic hypoxia and the depression of synaptic transmission in rat hippocampus
      after carotid artery occlusion.
AB  - The relationship between step reductions in inspired oxygen and the amplitude of
      evoked field excitatory postsynaptic potentials (fEPSPs) recorded from
      hippocampal CA1 neurons was examined in anaesthetized rats with a unilateral
      common carotid artery occlusion. The amplitudes of fEPSPs recorded from the
      hippocampus ipsilateral to the occlusion were significantly more depressed with
      hypoxia than were the fEPSPs recorded from the contralateral hippocampus. The
      adenosine A1-selective antagonist, 8-cyclopentyl-1,3-dimethylxanthine (8-CPT),
      blunted the hypoxic depression of the fEPSP. Tissue partial pressure of oxygen
      (Ptiss,O2) was measured in the ipsilateral and contralateral hippocampus using
      glass Clark-style microelectrodes. Ptiss,O2 fell to similar levels as a function
      of inspired oxygen in the ipsilateral and contralateral hippocampus, and in the
      ipsilateral hippocampus after administration of 8-CPT. Hippocampal blood flow
      (HBF) was measured using laser Doppler flowmetry. A decline in HBF was associated
      with systemic hypoxia in both hippocampi. HBF, as a function of inspired oxygen,
      fell significantly more in the ipsilateral than in the contralateral hippocampus.
      We conclude that endogenous adenosine acting at the neuronal A1 receptor plays a
      major role in the depression of synaptic transmission during hypoxic ischaemia.
      The greater susceptibility of the fEPSP in the ipsilateral hippocampus to
      systemic hypoxia cannot be explained entirely by differences in Ptiss,O2 or HBF
      between the two hemispheres.

PMID- 12807995
TI  - Within-breath control of genioglossal muscle activation in humans: effect of
      sleep-wake state.
AB  - Pharyngeal dilator muscles are clearly important in the pathogenesis of
      obstructive sleep apnoea syndrome. Substantial data support the role of a local
      negative pressure reflex in modifying genioglossal activation across inspiration
      during wakefulness. Using a model of passive negative pressure ventilation, we
      have previously reported a tight relationship between varying intrapharyngeal
      negative pressures and genioglossal muscle activation (GGEMG) during wakefulness.
      In this study, we used this model to examine the slope of the relationship
      between epiglottic pressure (Pepi) and GGEMG, during stable NREM sleep and the
      transition from wakefulness to sleep. We found that there was a constant
      relationship between negative epiglottic pressure and GGEMG during both basal
      breathing (BB) and negative pressure ventilation (NPV) during wakefulness (slope
      GGEMG/Pepi 1.86+/-0.3 vs. 1.79+/-0.3 arbitrary units (a.u.) cmH2O(-1)). However,
      while this relationship remained stable during NREM sleep during BB, it was
      markedly reduced during NPV during sleep (2.27+/-0.4 vs. 0.58+/-0.1 a.u. cmH2O(
      1)). This was associated with a markedly higher pharyngeal airflow resistance
      during sleep during NPV. At the transition from wakefulness to sleep there was
      also a greater reduction in peak GGEMG seen during NPV than during BB. These data
      suggest that while the negative pressure reflex is able to maintain GGEMG during
      passive NPV during wakefulness, this reflex is unable to do so during sleep. The
      loss of this protective mechanism during sleep suggests that an airway dependent
      upon such mechanisms (as in the patient with sleep apnoea) will be prone to
      collapse during sleep.

PMID- 12807996
TI  - Cilostazol prevents tumor necrosis factor-alpha-induced cell death by suppression
      of phosphatase and tensin homolog deleted from chromosome 10 phosphorylation and
      activation of Akt/cyclic AMP response element-binding protein phosphorylation.
AB  - This study examines the signaling mechanism by which cilostazol prevents neuronal
      cell death. Cilostazol ( approximately 0.1-100 microM) prevented tumor necrosis
      factor-alpha (TNF-alpha)-induced decrease in viability of SK-N-SH and HCN-1A
      cells, which was antagonized by 1 microM iberiotoxin, a maxi-K channel blocker.
      TNF-alpha did not suppress the viability of the U87-MG cell, a phosphatase and
      tensin homolog deleted from chromosome 10 (PTEN)-null glioblastoma cell, but it
      did decrease viability of U87-MG cells transfected with expression vectors for
      the sense PTEN, and this decrease was also prevented by cilostazol. Cilostazol as
      well as 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)
      2H-benzimidazol-2-one (NS-1619) and (3S)(+)-(5-chloro-2-methoxyphenyl)-1,3
      dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one (BMS 204352), maxi-K channel
      openers, prevented increased DNA fragmentation evoked by TNF-alpha, which were
      antagonizable by iberiotoxin. TNF-alpha-induced increased PTEN phosphorylation
      and decreased Akt/cyclic AMP response element-binding protein (CREB)
      phosphorylation were significantly prevented by cilostazol, those of which were
      antagonized by both iberiotoxin and paxilline, maxi-K channel blockers. The same
      results were evident in U87-MG cells transfected with expression vectors for
      sense PTEN. Cilostazol increases the K+ current in SK-N-SH cells by activating
      maxi-K channels without affecting the ATP-sensitive K+ channel. Thus, our results
      for the first time provide evidence that cilostazol prevents TNF-alpha-induced
      cell death by suppression of PTEN phosphorylation and activation of Akt/CREB
      phosphorylation via mediation of the maxi-K channel opening.

PMID- 12807997
TI  - Functional and binding characterizations of urotensin II-related peptides in
      human and rat urotensin II-receptor assay.
AB  - Urotensin II (U-II; cyclo5-10[H-Glu-Thr-Pro-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH])
      is a potent vasoconstrictor in mammals, and it is postulated that it plays a
      central role in cardiovascular homeostasis. Thus, we initiated a structure-to
      function analysis of this peptide characterized by a N-terminal tail and a cyclic
      core formed through a disulfide bridging. A total of 41 analogs focusing on these
      characteristics were developed and evaluated using a binding assay on membranes
      from a stable HEK-293 cell line containing the human or rat U-II receptor, a
      functional assay for Ca2+ mobilization on transiently transfected CHO-K1 cells
      with the human or rat U-II receptor, and a rat thoracic aorta bioassay. At first,
      the focus was applied on peptide compounds containing exocyclic modifications.
      From this series, it appeared that only valine-11 played a significant role
      although it is not an essential amino acid. Similarly, endocyclic and ring
      transformations of hU-II were also studied. In most cases, a detrimental effect
      on affinity and biological activity was observed. However, two compounds,
      [Tyr6]hU-II and [Phe9]hU-II, retained affinity and activity. So far, our binding,
      functional, and pharmacological data clearly demonstrated the minor contribution
      of the N-terminal segment and the essential role of the cyclic structure. More
      particularly, three residues within the loop, i.e., Trp-7, Lys-8, and Tyr-9, are
      required for receptor recognition and activation. This three-pole feature, kept
      by the disulfide bond in a correct spatial arrangement, appears as the key
      pharmacophore for the U-II receptor.

PMID- 12807998
TI  - Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and
      healthy subjects.
AB  - Long-term treatment with ibuprofen twice daily, at doses that achieve peak plasma
      concentration (Cmax) >50 microg/ml, slows progression of lung disease in patients
      with cystic fibrosis (CF). Previous data suggest that Cmax >50 microg/ml is
      associated with a reduction in neutrophil (PMN) migration into the lung and that
      lower concentrations are associated with an increase in PMN migration. To
      estimate the threshold concentration at which ibuprofen is associated with a
      decrease in PMN migration in vivo, we measured the PMN content of oral mucosal
      washes in 35 healthy (age 19-40 years) and 16 CF (age 18-32 years) subjects who
      took ibuprofen twice daily for 10 days in doses that achieved Cmax 8 to 90
      microg/ml. Cmax >50 microg/ml was associated with a 31 +/- 7% (mean +/- S.E.M.)
      reduction in PMNs in CF (n = 11, p < 0.001) and 25 +/- 6% reduction in PMNs in
      healthy subjects (n = 16, p < 0.001). Increasing concentrations above 50
      microg/ml was not associated with a greater decrease in PMNs. The reduction in
      PMN migration was consistently present 12 h after a dose, but not after 24 h.
      Cmax <50 microg/ml was associated with an increase in PMNs of approximately 40%.
      These results suggest that Cmax >50 microg/ml and twice daily dosing of ibuprofen
      are required to decrease PMN migration, and reinforce the current recommendation
      that pharmacokinetics should be performed in CF patients prescribed ibuprofen.

PMID- 12807999
TI  - Contribution of lymphatically transported testosterone undecanoate to the
      systemic exposure of testosterone after oral administration of two andriol
      formulations in conscious lymph duct-cannulated dogs.
AB  - Orally administered testosterone (T) is ineffective in the treatment of male
      androgen deficiency syndromes due to extensive presystemic first-pass metabolism.
      In contrast, the lipophilic long-chain ester testosterone undecanoate (TU)
      exhibits androgenic activity that has been attributed to formation of T via
      systemic hydrolysis of lymphatically transported TU. However, there are no
      definitive data regarding the oral bioavailability of TU or the extent to which
      lymphatically transported TU contributes to the systemic availability of T after
      oral TU administration. This report describes the application of stable isotope
      methodology in a thoracic lymph duct-cannulated dog model to study the oral
      bioavailability and lymphatic transport of TU after postprandial administration.
      When administered as either Andriol or Andriol Testocaps, the mean (+/-S.E., n =
      4) absolute bioavailability of TU was 3.25 +/- 0.48 and 2.88 +/- 0.88%,
      respectively, and lymphatically transported TU accounted for between 91.5 and
      99.7% of the systemically available ester. Model-independent pharmacokinetic
      analysis indicated that 83.6 +/- 1.6 and 84.1 +/- 8.2% of the systemically
      available T, resulting from Andriol or Andriol Testocaps, respectively, was due
      to systemic hydrolysis of lymphatically transported TU. These data demonstrate
      that intestinal lymphatic transport of TU produces increased systemic exposure of
      T by avoiding the extensive first-pass effect responsible for the inactivation of
      T after oral administration.

PMID- 12808000
TI  - Neuronal necrosis inhibition by insulin through protein kinase C activation.
AB  - In the serum-free culture of rat embryonic neurons, most neurons rapidly died by
      necrosis, which was revealed by propidium iodide (PI)-positive staining as early
      as 3 h after the start of culture and by marked membrane disruption and
      mitochondrial swelling in transmission electron microscopic (TEM) analysis.
      However, neither nuclear condensation/fragmentation stained with Hoechst 33342
      nor activated caspase-3-like immunoreactivity was observed. In the serum-deprived
      culture, on the other hand, neurons showed apoptotic features, such as caspase-3
      activation and nuclear damages in TEM analysis. Insulin at relatively higher
      concentrations, up to 100 microg/ml, ameliorated the rapid decrease in survival
      activity measured with 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4
      disulfophenyl)-2H-tetrazolium, monosodium salt WST-8 assay and PI staining in the
      serum-free culture, despite the fact that brain-derived neurotrophic factor and
      insulin-like growth factor-I had no survival effect even at concentrations up to
      100 microg/ml. Insulin-induced survival effects were abolished by the protein
      kinase C (PKC) inhibitor calphostin C but not by the phosphatidyl inositol-3-OH
      kinase inhibitor wortmannin or the mitogen-activated protein kinase inhibitors
      PD98059 or U0126. Insulin significantly stimulated the PKC activity in cell
      lysates and suppressed the mitochondrial swelling and membrane disruption in TEM
      analysis in a calphostin C-reversible manner. All of these findings suggest that
      insulin inhibited the neuronal necrosis resistant to known neurotrophic factors
      under the serum-free culture through PKC mechanisms.

PMID- 12808001
TI  - Aromatase is the major enzyme metabolizing buprenorphine in human placenta.
AB  - Buprenorphine (BUP) is a partial opiate agonist used for treatment of the adult
      and the pregnant addicted to this class of narcotics. The kinetic parameters for
      transplacental transfer and the metabolism of BUP during its perfusion in a
      placental lobule were the subject of an earlier report from our laboratory. The
      aim of this investigation is to identify and characterize the enzyme catalyzing
      the metabolism of BUP in term human placenta. Norbuprenorphine (norBUP) is the
      only metabolite formed as determined by high performance liquid chromatography
      and mass spectrometry. The activity of the enzyme responsible for BUP metabolism
      is highest in the microsomal fraction and lowest in the cytosolic, with the
      mitochondrial in between. Compounds with selective affinity to the enzyme
      aromatase (CYP 19), namely 4-hydroxyandrostenedione and aminoglutethimide, caused
      >70% inhibition of norBUP formation. Monoclonal antibodies raised against CYP 19
      were the most potent inhibitors of BUP dealkylation. A comparison between the
      data obtained from the saturation isotherm for BUP dealkylation by placental
      microsomes and a commercially available system of cDNA-expressed CYP 19 indicated
      similar kinetic parameters, with apparent Km values of 12 +/- 4.0 and 14 +/- 8.0
      microM, respectively. Therefore, aromatase is the major enzyme catalyzing the
      biotransformation of BUP to norBUP in term human placentas obtained from healthy
      pregnancies. The minor involvement of other cytochrome P450 isoforms or enzyme(s)
      in the metabolism of BUP in placental tissue cannot be ruled out.

PMID- 12808002
TI  - Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays.
AB  - Corticosteroid (CS) pharmacogenomics was studied using gene microarrays in rat
      liver. Methylprednisolone (MPL) was administered intravenously at 50 mg/kg. Rats
      were sacrificed and liver excised at 17 time points over 72 h. RNAs from
      individual livers were used to query Affymetrix GeneChips that contain sequences
      for 8000 genes. Cluster analysis revealed six temporal patterns consisting of 197
      CS-responsive probes representing 143 genes. Based on our fifth-generation model
      of CS pharmacokinetics/pharmacodynamics (PK/PD), mechanistic models were
      developed to describe the time pattern for each CS-responsive gene. Two clusters
      showed increased expression with different effect duration. PK/PD models assuming
      CS stimulation of mRNA synthesis were applied. Another two clusters showed an
      initial decline followed by delayed increase, suggesting two mechanisms might be
      involved jointly. The initial suppression was captured by CS inhibition of mRNA
      synthesis or stimulation of degradation. CS may also stimulate the production of
      a biosignal (transcription factors or other hormones), which can cause secondary
      induction of the target mRNA. One cluster showed a very abrupt increase in
      message followed by rapid decrease. These genes were lymphocytic in origin and
      were modeled combining the fast gene induction effect of CS in lymphoid cells and
      its direct lymphocyte trafficking effect. Another cluster showed reduction
      persisting for 18 h, which was described by CS inhibition of mRNA synthesis. Our
      results reveal the marked diversity of genes regulated by CS via a limited array
      of mechanisms. These PK/PD models provide quantitation of CS pharmacogenomics and
      new hypotheses regarding understanding of diverse mechanisms of CS receptor-gene
      mediated action.

PMID- 12808003
TI  - Inhibition of canine (NCX1.1) and Drosophila (CALX1.1) Na(+)-Ca(2+) exchangers by
      7-chloro-3,5-dihydro-5-phenyl-1H-4,1-benzothiazepine-2-one (CGP-37157).
AB  - The electrophysiological effects of the benzothiazepine 7-chloro-3,5-dihydro-5
      phenyl-1H-4,1-benzothiazepine-2-one (CGP-37157) (CGP) were investigated on the
      canine (NCX1.1) and Drosophila (CALX1.1) plasmalemmal Na+-Ca2+ exchangers. These
      exchangers were selected for study because they show opposite responses to
      cytoplasmic regulatory Ca2+, thereby allowing us to examine the role of this
      regulatory mechanism in the inhibitory effects of CGP. CGP blocked Na+-Ca2+
      exchange current mediated by both transporters with moderate potency (IC50 values
      = approximately 3-17 microM) compared with other recently reported blockers of
      Na+-Ca2+ exchange [e.g., 2-[4-[2,5-difluorophenyl) methoxy]phenoxy]phenoxy]-5
      ethoxyaniline (KB-R7943) and 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea
      (SEA0400)]. Experiments using alpha-chymotrypsin to remove autoregulation of Na+
      Ca2+ exchange showed that block by CGP was reduced, suggesting that part of the
      effects of this drug may require intact ionic regulatory mechanisms. For NCX1.1,
      the inhibition produced by CGP was greater for outward Na+-Ca2+ exchange currents
      compared with inward currents. When CALX1.1 was examined, the extent of
      inhibition was similar for both inward and outward exchange currents. Although
      the extent and potency of CGP-mediated inhibition of Na+-Ca2+ exchange are less
      than those observed with SEA0400 and KB-R7943, our data demonstrate that CGP
      constitutes a novel class of plasmalemmal Na+-Ca2+ exchange inhibitors. Moreover,
      the widespread use of CGP as a selective mitochondrial Na+-Ca2+ exchange
      inhibitor should be reconsidered in light of these additional inhibitory effects.

PMID- 12808004
TI  - Multiple injections of pegylated liposomal Doxorubicin: pharmacokinetics and
      therapeutic activity.
AB  - Effects of multiple injections of liposomal doxorubicin on pharmacokinetics,
      therapeutic outcome, and toxicity were studied in mice using different dosing
      schedules and dose intensities. Biodistribution of doxorubicin to the cutaneous
      tissues of mice (skin and paws) and to orthotopically implanted mammary tumors
      (4T1) was examined. Weekly intravenous administration of pegylated (STEALTH)
      liposomal doxorubicin (SL-DXR) at a dose of 9 mg/kg (every week x 4 doses)
      resulted in accumulation of doxorubicin in cutaneous tissues of mice and
      development of lesions resembling palmar-plantar erythrodysesthesia (PPE).
      Lengthening the dose interval to every 2 weeks x 4 doses reduced the accumulation
      of doxorubicin and lowered the incidence of PPE-like lesions. A dose interval of
      every 4 weeks x 4 resulted in complete clearance of doxorubicin from tissues
      between subsequent doses and a negligible incidence of PPE-like lesions. Doses of
      9 mg/kg SL-DXR given at every week x 2 or every 2 weeks x 2 had similar
      therapeutic activities, whereas prolonging the dose interval to every 4 weeks x 2
      reduced therapeutic activity. Pharmacokinetics, biodistribution, and therapeutic
      activity were studied in tumor-bearing mice for three dose schedules having the
      same dose intensity (4.5 mg/kg every 3 days x 4, 9 mg/kg every week x 2, or 18
      mg/kg every 2 weeks x 1). For these schedules, larger doses administered less
      often tended to be superior therapeutically to smaller doses given more often.
      These data provide the first pharmacokinetic measurements of doxorubicin
      concentrations in cutaneous tissues and tumors with repeat administration of
      liposomal formulations, and they provide a useful model for the study of factors
      leading to PPE in humans.

PMID- 12808005
TI  - Differential regulation of the endocannabinoids anandamide and 2
      arachidonylglycerol within the limbic forebrain by dopamine receptor activity.
AB  - Glutamatergic synaptic transmission within the striatum and prefrontal cortex
      regulates the neuronal synthesis of endocannabinoids. Because a primary role of
      dopamine is to modulate this excitatory transmission, we tested the hypothesis
      that dopaminergic transmission modulates endocannabinoid content in the limbic
      forebrain. Liquid chromatography/mass spectrometry was used to determine
      endogenous anandamide and 2-arachidonylglycerol (2-AG) contents within the limbic
      forebrain of mice after pharmacological manipulation of dopaminergic
      transmission. Increasing synaptic dopamine concentrations with methylphenidate
      significantly and dose dependently decreased both anandamide and 2-AG content.
      The selective dopamine reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]
      4-(3-phenylpropyl)piperazine (GBR 12909) also significantly decreased anandamide
      and tended to decrease 2-AG content. The D1 receptor antagonist R-(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390)
      increased and the D1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl
      1H-3-benzazepine (SKF 33939) decreased anandamide content. 2-AG content was
      unaffected by SCH 23390 but was significantly increased by the D2 receptor
      antagonist eticlopride, which had no effect on anandamide content. The D2 agonist
      quinpirole had a biphasic effect on anandamide content with low, autoreceptor
      preferring doses increasing anandamide and higher doses decreasing it back toward
      control. Quinpirole did not significantly affect 2-AG content. Together, these
      data indicate that endogenous dopamine exerts a differential, net suppressive
      effect upon anandamide and 2-AG content via activation of D1 and D2 receptors,
      respectively. These data are consistent with the hypothesis that modulation of
      endocannabinoid content by dopamine is secondary to changes in glutamatergic
      transmission, and they provide a pharmacological framework for the rational
      development of endocannabinoid-based therapeutic interventions for dopamine
      related neuropsychiatric disorders.

PMID- 12808006
TI  - Evaluation of a social-skills training group intervention with children treated
      for brain tumors: a pilot study.
AB  - OBJECTIVE: To evaluate the effectiveness of a manual-based, social-skills
      training, group intervention to improve social skills and social functioning of
      children treated for brain tumors, and to assess the impact of cognitive
      functioning on the effectiveness of the intervention. METHODS: Three social
      skills training group interventions, each comprised of 5 to 7 children ages 8 to
      14 years, were conducted. A parent component was included. In total, 13 children
      and their parents and teachers completed standard measures prior to and 9 months
      after the intervention. Children participated in a neuropsychological test
      battery at baseline. RESULTS: Social skills and social functioning variables
      changed in the direction of improved functioning, with several scores showing
      significant improvement from baseline to the follow-up assessment. Small to
      medium effect sizes were documented. Higher verbal and nonverbal functioning were
      associated with greater improvement. CONCLUSIONS: Findings are suggestive of the
      potential effectiveness of social-skills training in groups for children with
      brain tumors. Multisite, randomized, controlled studies are recommended as the
      next step.

PMID- 12808007
TI  - Martin P. Levin Distinguished Mentorship Award: reflections on mentorship in
      pediatric psychology: key issues and implications.

PMID- 12808008
TI  - Clinical case study: pediatric residents' discussions of and interventions for
      children's behavioral and emotional problems.
AB  - OBJECTIVE: To examine the effects of a screening instrument and parent handouts
      on pediatric residents' discussions of and interventions for children's
      behavioral and emotional problems. METHOD: Four pediatric residents and 52 parent
      child dyads attending an ambulatory pediatric primary care clinic participated in
      the study. We used a multiple baseline design across residents. We assessed the
      effect of the interventions by measuring nine target behaviors of the pediatric
      residents. RESULTS: After being trained to use the screening instrument,
      residents increased the number and variety of questions they asked regarding
      behavioral and emotional issues. Residents' attempts at intervention showed small
      but consistent increases when handouts on behavior management procedures were
      made available for distribution to parents. CONCLUSIONS: The use of a screening
      instrument in pediatric primary care shows promise for increasing discussions
      between residents and parents about children's behavioral and emotional issues.
      Further research should examine strategies to improve pediatric residents'
      attempts at intervention for behavioral and emotional problems in children.

PMID- 12808009
TI  - Medication adherence in pediatric asthma: reasoning, responsibility, and
      behavior.
AB  - OBJECTIVE: To assess child adherence to preventive asthma medications; to
      investigate relations between knowledge, reasoning about asthma, and
      responsibility for management and adherence; and to determine the association
      between adherence and morbidity. METHODS: Participants were 106 children with
      asthma and their parents. Medication adherence was electronically monitored for 1
      month. Participants completed self-report measures. Children were interviewed to
      assess reasoning about asthma. RESULTS: Children's adherence was approximately
      48% of prescribed doses. Adherence was negatively related to age (r = -.21, p
      <.05); minority status, F(1, 98) = 7.55, p <.01; and morbidity (r = -.26, p
      <.01). Age was associated with increased child knowledge (r =.47, p <.001),
      reasoning about asthma (tau =.23, p <.01), and responsibility for asthma
      management (r =.44, p <.01). These variables were not associated with adherence.
      CONCLUSIONS: Although older children know more about asthma and assume more
      responsibility for disease management, their adherence is lower than that of
      younger children. No association was found between adherence and child knowledge,
      reasoning about asthma, or responsibility for asthma management.

PMID- 12808010
TI  - Social support, knowledge, and self-efficacy as correlates of osteoporosis
      preventive behaviors among preadolescent females.
AB  - OBJECTIVE: To develop and test a model based on Bandura's social cognitive theory
      to predict healthy lifestyle behaviors for the prevention of osteoporosis.
      METHODS: Participants were 354 girls, ages 8-11 years, recruited from area Girl
      Scout troops. Baseline data from a randomized trial of behavioral interventions
      are presented. Measures of social support, knowledge, self-efficacy, dietary
      calcium intake, and weight-bearing physical activity (WBPA) were obtained via
      interviews and self-administered questionnaires. RESULTS: A structural equation
      model was tested and fit the data well. Family social support, perceived self
      efficacy for eating a calcium-rich diet, and knowledge of WBPA significantly
      predicted calcium intake. Friend and family support for exercise predicted WBPA.
      Self-efficacy partially mediated the relationship between family support and
      calcium intake, as confirmed by Holmbeck's post-hoc probing strategy (2002).
      CONCLUSIONS: Suggestions are made for primary prevention interventions such as
      parent and peer involvement, health education, and problem-solving training.

PMID- 12808011
TI  - Brief report: adjustment to juvenile rheumatoid arthritis: a family systems
      perspective.
AB  - OBJECTIVE: To examine the relations of the family environment to adjustment to
      juvenile rheumatoid arthritis (JRA), and to examine how those relations are
      influenced by child sex and age. METHOD: Ninety-four children with JRA completed
      a questionnaire on family environment and adjustment. RESULTS: Family cohesion
      was related to good adjustment, whereas family conflict was related to poor
      adjustment. Some relations of family cohesion to adjustment were stronger for
      younger than for older children. The relations of child autonomy to adjustment
      depended on child sex and age. CONCLUSION: The relations of the family
      environment to adjustment to JRA are dependent on child sex and age.

PMID- 12808012
TI  - The reliability of reports of medical adherence from children with HIV and their
      adult caregivers.
AB  - OBJECTIVE: To compare children's reports of their medication adherence to those
      of their adult caregivers. METHOD: Several indicators of medication adherence
      were assessed for 48 adult-child dyads. Kappa statistics were calculated as
      measures of agreement. RESULTS: Adherence problems were common, although the
      level of agreement between the child and the adult was quite low (kappas for
      adherence variables ranged from .05 to .32). Compared to adult-child dyads that
      agreed, dyads that disagreed tended to include older children who had more
      responsibility for managing their own medications. CONCLUSIONS: Both researchers
      and clinicians would benefit from acquiring information on children's adherence
      from multiple sources.

PMID- 12808013
TI  - Daily stress and mood and their association with pain, health-care use, and
      school activity in adolescents with sickle cell disease.
AB  - OBJECTIVE: To determine the extent to which daily stress and mood are associated
      with pain, health-care use, and school activity in adolescents with sickle cell
      disease (SCD). METHOD: Adolescents with SCD (n = 37; aged 13 to 17 years)
      completed daily diaries assessing pain, stress, mood, activity, and health-care
      use for up to 6 months. Multilevel modeling was used to analyze the data.
      RESULTS: Daily increases in stress and negative mood were associated with
      increases in same-day pain, health-care use, and reductions in school and social
      activity. Increases in positive mood were associated with decreases in pain, less
      health-care use, and more activity participation. Notably, pain was predictive of
      higher stress and lower positive mood on subsequent days. CONCLUSION: Pain in
      adolescents with SCD is stressful and may lead to alterations in mood states.
      Understanding the way in which these variables relate to health-care use and
      activity may lead to improved pain management approaches.

PMID- 12808015
TI  - Destroying myth and wonder. By Caveman.

PMID- 12808016
TI  - 'Eph'ective signaling: forward, reverse and crosstalk.
AB  - The Eph receptors comprise the largest group of receptor tyrosine kinases and are
      found in a wide variety of cell types in developing and mature tissues. Their
      ligands are the ephrins, a family of membrane-bound proteins found in lipid
      rafts. In the past decade, Eph receptors and ephrins have been implicated in a
      vast array of cellular processes. Unlike other receptor tyrosine kinases,
      however, the Eph receptors seem to be geared towards regulating cell shape and
      movement rather than proliferation. Studies have uncovered intricate signaling
      networks that center around the ligand-receptor complex, and this may account for
      the broad repertoire of functions of Eph proteins. Deciphering the bi-directional
      pathways emanating from an Eph receptor-ephrin complex will not only help us to
      understand basic biological processes, but may also provide important insight
      into disease.

PMID- 12808017
TI  - Fluorescence in situ hybridization: past, present and future.
AB  - Fluorescence in situ hybridization (FISH), the assay of choice for localization
      of specific nucleic acids sequences in native context, is a 20-year-old
      technology that has developed continuously. Over its maturation, various
      methodologies and modifications have been introduced to optimize the detection of
      DNA and RNA. The pervasiveness of this technique is largely because of its wide
      variety of applications and the relative ease of implementation and performance
      of in situ studies. Although the basic principles of FISH have remained
      unchanged, high-sensitivity detection, simultaneous assay of multiple species,
      and automated data collection and analysis have advanced the field significantly.
      The introduction of FISH surpassed previously available technology to become a
      foremost biological assay. Key methodological advances have allowed facile
      preparation of low-noise hybridization probes, and technological breakthroughs
      now permit multi-target visualization and quantitative analysis - both factors
      that have made FISH accessible to all and applicable to any investigation of
      nucleic acids. In the future, this technique is likely to have significant
      further impact on live-cell imaging and on medical diagnostics.

PMID- 12808018
TI  - Intramembrane proteolysis by presenilin and presenilin-like proteases.
AB  - Regulated intramembrane proteolysis is a novel mechanism involving proteases that
      hydrolyze their substrates in a hydrophobic environment. Presenilin (PS) 1 and PS
      2 are required for intramembrane cleavage of an increasing number of type I
      membrane proteins, including the amyloid precursor protein of Alzheimer's disease
      and the Notch receptor, which signals during differentiation and development.
      Mutagenesis, affinity labeling, biochemical isolation, and reconstitution in
      cells reveal that PS, in complex with co-factors nicastrin, APH-1 and PEN-2,
      apparently contains the active site of gamma-secretase, a novel membrane aspartyl
      protease. In addition, other related aspartyl proteases have been identified.
      These include members of the type-4 prepilin peptidase family in bacteria, which
      are known proteases and carry a GD motif conserved in PS. A group of multi-pass
      membrane proteins found in eukaryotes also contain YD and LGXGD motifs in two
      transmembrane domains that are conserved in PS and postulated to constitute an
      aspartyl protease active site. Among these is signal peptide peptidase (SPP),
      which cleaves remnant signal peptides derived from signal-peptidase-mediated
      ectodomain shedding. SPP cuts type II membrane proteins, illustrating that PS
      like proteases play a key role in intramembrane proteolysis of single-pass
      membrane proteins oriented in either direction.

PMID- 12808019
TI  - Thrombospondin signaling through the calreticulin/LDL receptor-related protein co
      complex stimulates random and directed cell migration.
AB  - The matricellular extracellular matrix protein thrombospondin-1 (TSP1) stimulates
      focal adhesion disassembly through a sequence (known as the hep I peptide) in its
      heparin-binding domain. This mediates signaling through a receptor co-complex
      involving calreticulin and low-density lipoprotein (LDL) receptor-related protein
      (LRP). We postulate that this transition to an intermediate adhesive state
      enhances cellular responses to dynamic environmental conditions. Since cell
      adhesion dynamics affect cell motility, we asked whether TSP1/hep I-induced
      intermediate adhesion alters cell migration. Using both transwell and Dunn
      chamber assays, we demonstrate that TSP1 and hep I gradients stimulate
      endothelial cell chemotaxis. Treatment with focal adhesion-labilizing
      concentrations of TSP1/hep I in the absence of a gradient enhances endothelial
      cell random migration, or chemokinesis, associated with an increase in cells
      migrating, migration speed, and total cellular displacement. Calreticulin-null
      and LRP-null fibroblasts do not migrate in response to TSP1/hep I, nor do
      endothelial cells treated with the LRP inhibitor receptor-associated protein
      (RAP). Furthermore, TSP1/hep I-induced focal adhesion disassembly is associated
      with reduced chemotaxis to basic fibroblast growth factor (bFGF) but enhanced
      chemotaxis to acidic (a)FGF, suggesting differential modulation of growth factor
      induced migration. Thus, TSP1/hep I stimulation of intermediate adhesion
      regulates the migratory phenotype of endothelial cells and fibroblasts,
      suggesting a role for TSP1 in remodeling responses.

PMID- 12808020
TI  - Collagen-IV and laminin-1 regulate estrogen receptor alpha expression and
      function in mouse mammary epithelial cells.
AB  - The expression level and functional activity of estrogen receptor alpha is an
      important determinant of breast physiology and breast cancer treatment. However,
      it has been difficult to identify the signals that regulate estrogen receptor
      because cultured mammary epithelial cells generally do not respond to estrogenic
      signals. Here, we use a combination of two- and three-dimensional culture systems
      to dissect the extracellular signals that control endogenous estrogen receptor
      alpha. Its expression was greatly reduced when primary mammary epithelial cells
      were placed on tissue culture plastic; however, the presence of a reconstituted
      basement membrane in combination with lactogenic hormones partially prevented
      this decrease. Estrogen receptor alpha expression in primary mammary fibroblasts
      was not altered by these culture conditions, indicating that its regulation is
      cell type specific. Moreover, estrogen receptor-dependent reporter gene
      expression, as well as estrogen receptor alpha levels, were increased threefold
      in a functionally normal mammary epithelial cell line when reconstituted basement
      membrane was added to the medium. This regulatory effect of reconstituted
      basement membrane was reproduced by two of its components, collagen-IV and
      laminin-1, and it was blocked by antibodies against alpha2, alpha6 and beta1
      integrin subunits. Our results indicate that integrin-mediated response to
      specific basement membrane components, rather than cell rounding or cell growth
      arrest induced by reconstituted basement membrane, is critical in the regulation
      of estrogen receptor alpha expression and function in mammary epithelial cells.

PMID- 12808021
TI  - Stimulation of MMP-7 (matrilysin) by Helicobacter pylori in human gastric
      epithelial cells: role in epithelial cell migration.
AB  - Epithelial cell responses to bacterial infection include induction of matrix
      metalloproteinase 7 (MMP-7). Here, we identify increased MMP-7 expression in the
      gastric epithelium in response to the oncogenic bacterium Helicobacter pylori,
      and report on the mechanisms and consequences for gastric epithelial cell
      migration. In patients infected with H. pylori, there was increased MMP-7 in
      gastric biopsies detected by western blot. MMP-7 was localized to the advancing
      edge of migrating gastric epithelial cell colonies, including lamellipodia. Rates
      of spreading of gastric gland cells were higher in H. pylori-infected cultures
      compared with control, and this was inhibited by antisense oligonucleotides to
      MMP-7. Complementary data were obtained in a gastric cancer cell line (AGS
      cells). In the latter, H. pylori induced expression of an MMP-7-luciferase
      promoter/reporter vector through mechanisms that involved activation of Rho and
      Rac. RhoA acted through activation of both NF-kappaB and AP-1, whereas Rac
      activated NF-kappaB but not AP-1. MMP-7 is commonly upregulated in gastric
      cancer; since H. pylori is a recognized gastric carcinogen, the data suggest a
      new mechanism by which the bacterium might predispose towards gastric neoplasia.

PMID- 12808022
TI  - Consequences of nonadaptive alterations in cancer.

PMID- 12808023
TI  - Drosophila MCM10 interacts with members of the prereplication complex and is
      required for proper chromosome condensation.
AB  - Mcm10 is required for the initiation of DNA replication in Saccharomyces
      cerevisiae. We have cloned MCM10 from Drosophila melanogaster and show that it
      complements a ScMCM10 null mutant. Moreover, Mcm10 interacts with key members of
      the prereplication complex: Mcm2, Dup (Cdt1), and Orc2. Interactions were also
      detected between Mcm10 and itself, Cdc45, and Hp1. RNAi depletion of Orc2 and
      Mcm10 in KC cells results in loss of DNA content. Furthermore, depletion of
      Mcm10, Cdc45, Mcm2, Mcm5, and Orc2, respectively, results in aberrant chromosome
      condensation. The condensation defects observed resemble previously published
      reports for Orc2, Orc5, and Mcm4 mutants. Our results strengthen and extend the
      argument that the processes of chromatin condensation and DNA replication are
      linked.

PMID- 12808024
TI  - Tumor necrosis factor-alpha causes accumulation of a ubiquitinated form of
      hypoxia inducible factor-1alpha through a nuclear factor-kappaB-dependent
      pathway.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a regulator of metabolic adaptation to
      hypoxia. It is now appreciated that HIF-1alpha accumulation is achieved under
      normoxic conditions by various factors, such as TNF-alpha. Here, it was our
      intention to gain insight into the signaling mechanisms used by TNF-alpha to
      stimulate HIF-1alpha. In tubular LLC-PK1 or human embryonic kidney cells, TNF
      alpha induced accumulation of HIF-1alpha protein but not HIF-1alpha mRNA.
      Blocking nuclear factor (NF)-kappaB with sulfasalazine or expression of an
      IkappaB superrepressor attenuated HIF-1alpha accumulation, whereas transfection
      of active p50/p65-NF-kappaB subunits mimicked a TNF-alpha response. Experiments
      with actinomycin D and cycloheximide also pointed to a transcriptional and
      translational process in facilitating the TNF-alpha response. Interestingly, and
      in contrast to established hypoxic signaling concepts, TNF-alpha elicited HIF
      1alpha accumulation in a ubiquitinated form that still bound the von Hippel
      Lindau (pVHL) protein. These data indicate that HIF-1alpha accumulation by TNF
      alpha demands the NF-kappaB pathway, preserves ubiquitination of HIF-1alpha, and
      allows the HIF-1alpha-pVHL interaction.

PMID- 12808025
TI  - Pex15p of Saccharomyces cerevisiae provides a molecular basis for recruitment of
      the AAA peroxin Pex6p to peroxisomal membranes.
AB  - The gene products (peroxins) of at least 29 PEX genes are known to be necessary
      for peroxisome biogenesis but for most of them their precise function remains to
      be established. Here we show that Pex15p, an integral peroxisomal membrane
      protein, in vivo and in vitro binds the AAA peroxin Pex6p. This interaction
      functionally interconnects these two hitherto unrelated peroxins. Pex15p provides
      the mechanistic basis for the reversible targeting of Pex6p to peroxisomal
      membranes. We could demonstrate that the N-terminal part of Pex6p contains the
      binding site for Pex15p and that the two AAA cassettes D1 and D2 of Pex6p have
      opposite effects on this interaction. A point mutation in the Walker A motif of
      D1 (K489A) decreased the binding of Pex6p to Pex15p indicating that the
      interaction of Pex6p with Pex15p required binding of ATP. Mutations in Walker A
      (K778A) and B (D831Q) motifs of D2 abolished growth on oleate and led to a
      considerable larger fraction of peroxisome bound Pex6p. The nature of these
      mutations suggested that ATP-hydrolysis is required to disconnect Pex6p from
      Pex15p. On the basis of these results, we propose that Pex6p exerts at least part
      of its function by an ATP-dependent cycle of recruitment and release to and from
      Pex15p.

PMID- 12808026
TI  - She4p/Dim1p interacts with the motor domain of unconventional myosins in the
      budding yeast, Saccharomyces cerevisiae.
AB  - She4p/Dim1p, a member of the UNC-45/CRO1/She4p (UCS) domain-containing protein
      family, is required for endocytosis, polarization of actin cytoskeleton, and
      polarization of ASH1 mRNA in Saccharomyces cerevisiae. We show herein that
      She4p/Dim1p is involved in endocytosis and actin polarization through
      interactions with the type I myosins Myo3p and Myo5p. Two-hybrid and biochemical
      experiments showed that She4p/Dim1p interacts with the motor domain of Myo3/5p
      through its UCS domain. She4p/Dim1p was required for Myo5p localization to
      cortical patch-like structures. Using random mutagenesis of the motor region of
      MYO5, we identified four independent dominant point mutations that suppress the
      temperature-sensitive growth phenotype of the she4/dim1 null mutant. All of the
      amino acid substitutions caused by these mutations, V164I, N168I, N209S, and
      K377M, could suppress the defects of endocytosis and actin polarization of the
      she4/dim1 mutant as well. She4p/Dim1p also showed two-hybrid interactions with
      the motor domain of a type II myosin Myo1p and type V myosins Myo2p and Myo4p,
      and was required for proper localization of Myo4p, which regulates polarization
      of ASH1 mRNA. Our results suggest that She4p/Dim1p is required for structural
      integrity or regulation of the motor domain of unconventional myosins.

PMID- 12808027
TI  - ADP-ribosylation factor/COPI-dependent events at the endoplasmic reticulum-Golgi
      interface are regulated by the guanine nucleotide exchange factor GBF1.
AB  - ADP-ribosylation factor (ARF) mediated recruitment of COPI to membranes plays a
      central role in transport between the endoplasmic reticulum (ER) and the Golgi.
      The activation of ARFs is mediated by guanine nucleotide exchange factors (GEFs).
      Although several ARF-GEFs have been identified, the transport steps in which they
      function are still poorly understood. Here we report that GBF1, a member of the
      Sec7-domain family of GEFs, is responsible for the regulation of COPI-mediated
      events at the ER-Golgi interface. We show that GBF1 is essential for the
      formation, differentiation, and translocation of pre-Golgi intermediates and for
      the maintenance of Golgi integrity. We also show that the formation of transport
      competent ER-to-Golgi intermediates proceeds in two stages: first, a COPI
      independent event leads to the formation of an unstable compartment, which is
      rapidly reabsorbed in the absence of GBF1 activity. Second, the association of
      GBF1 with this compartment allows COPI recruitment and leads to its maturation
      into transport intermediates. The recruitment of GBF1 to this compartment is
      specifically inhibited by brefeldin A. Our findings imply that the continuous
      recruitment of GBF1 to spatially differentiated membrane domains is required for
      sustained membrane remodeling that underlies membrane traffic and Golgi
      biogenesis.

PMID- 12808028
TI  - RHAMM is a centrosomal protein that interacts with dynein and maintains spindle
      pole stability.
AB  - The receptor for hyaluronan-mediated motility (RHAMM), an acidic coiled coil
      protein, has previously been characterized as a cell surface receptor for
      hyaluronan, and a microtubule-associated intracellular hyaluronan binding
      protein. In this study, we demonstrate that a subset of cellular RHAMM localizes
      to the centrosome and functions in the maintenance of spindle integrity. We
      confirm a previous study showing that the amino terminus of RHAMM interacts with
      microtubules and further demonstrate that a separate carboxy-terminal domain is
      required for centrosomal targeting. This motif overlaps the defined hyaluronan
      binding domain and bears 72% identity to the dynein interaction domain of Xklp2.
      RHAMM antibodies coimmunprecipitate dynein IC from Xenopus and HeLa extracts.
      Deregulation of RHAMM expression inhibits mitotic progression and affects spindle
      architecture. Structure, localization, and function, along with phylogenetic
      analysis, suggests that RHAMM may be a new member of the TACC family. Thus, we
      demonstrate a novel centrosomal localization and mitotic spindle-stabilizing
      function for RHAMM. Moreover, we provide a potential mechanism for this function
      in that RHAMM may cross-link centrosomal microtubules, through a direct
      interaction with microtubules and an association with dynein.

PMID- 12808029
TI  - Tomographic evidence for continuous turnover of Golgi cisternae in Pichia
      pastoris.
AB  - The budding yeast Pichia pastoris contains ordered Golgi stacks next to discrete
      transitional endoplasmic reticulum (tER) sites, making this organism ideal for
      structure-function studies of the secretory pathway. Here, we have used P.
      pastoris to test various models for Golgi trafficking. The experimental approach
      was to analyze P. pastoris tER-Golgi units by using cryofixed and freeze
      substituted cells for electron microscope tomography, immunoelectron microscopy,
      and serial thin section analysis of entire cells. We find that tER sites and the
      adjacent Golgi stacks are enclosed in a ribosome-excluding "matrix." Each stack
      contains three to four cisternae, which can be classified as cis, medial, trans,
      or trans-Golgi network (TGN). No membrane continuities between compartments were
      detected. This work provides three major new insights. First, two types of
      transport vesicles accumulate at the tER-Golgi interface. Morphological analysis
      indicates that the center of the tER-Golgi interface contains COPII vesicles,
      whereas the periphery contains COPI vesicles. Second, fenestrae are absent from
      cis cisternae, but are present in medial through TGN cisternae. The number and
      distribution of the fenestrae suggest that they form at the edges of the medial
      cisternae and then migrate inward. Third, intact TGN cisternae apparently peel
      off from the Golgi stacks and persist for some time in the cytosol, and these
      "free-floating" TGN cisternae produce clathrin-coated vesicles. These
      observations are most readily explained by assuming that Golgi cisternae form at
      the cis face of the stack, progressively mature, and ultimately dissociate from
      the trans face of the stack.

PMID- 12808030
TI  - MTG1 codes for a conserved protein required for mitochondrial translation.
AB  - The MTG1 gene of Saccharomyces cerevisiae, corresponding to ORF YMR097c on
      chromosome XIII, codes for a mitochondrial protein essential for respiratory
      competence. A human homologue of Mtg1p capable of partially rescuing the
      respiratory deficiency of a yeast mtg1 mutant has also been localized in
      mitochondria. Mtg1p is a member of a family of GTPases with largely unknown
      functions. The respiratory deficiency of mtg1 mutants stems from a defect in
      mitochondrial protein synthesis. Mutations in the 21S rRNA locus are able to
      suppress the translation defect of mtg1 null mutants. This points to the 21S rRNA
      or the large ribosomal subunit as the most likely target of Mtg1p action. The
      presence of mature size 15S and 21S mitochondrial rRNAs in mtg1 mutants excludes
      Mtg1p from being involved in transcription or processing of these RNAs. More
      likely, Mtg1p functions in assembly of the large ribosomal subunit. This is
      consistent with the peripheral localization of Mtg1p on the matrix side of the
      inner membrane and the results of in vivo mitochondrial translation assays in a
      temperature-sensitive mtg1 mutant.

PMID- 12808031
TI  - Mdm30 is an F-box protein required for maintenance of fusion-competent
      mitochondria in yeast.
AB  - Mitochondrial fusion and fission play important roles for mitochondrial
      morphology and function. We identified Mdm30 as a novel component required for
      maintenance of fusion-competent mitochondria in yeast. The Mdm30 sequence
      contains an F-box motif that is commonly found in subunits of Skp1-Cdc53-F-box
      protein ubiquitin ligases. A fraction of Mdm30 is associated with mitochondria.
      Cells lacking Mdm30 contain highly aggregated or fragmented mitochondria instead
      of the branched tubular network seen in wild-type cells. Deltamdm30 cells lose
      mitochondrial DNA at elevated temperature and fail to fuse mitochondria in
      zygotes at all temperatures. These defects are rescued by deletion of DNM1, a
      gene encoding a component of the mitochondrial division machinery. The protein
      level of Fzo1, a key component of the mitochondrial fusion machinery, is
      regulated by Mdm30. Elevated Fzo1 levels in cells lacking Mdm30 or in cells
      overexpressing Fzo1 from a heterologous promoter induce mitochondrial aggregation
      in a similar manner. Our results suggest that Mdm30 controls mitochondrial shape
      by regulating the steady-state level of Fzo1 and point to a connection of the
      ubiquitin/26S proteasome system and mitochondria.

PMID- 12808032
TI  - Identifying phase-specific genes in the fungal pathogen Histoplasma capsulatum
      using a genomic shotgun microarray.
AB  - A fundamental feature of the fungal pathogen Histoplasma capsulatum is its
      ability to shift from a mycelial phase in the soil to a yeast phase in its human
      host. Each form plays a critical role in infection and disease, but little is
      understood about how these two morphologic phases are established and maintained.
      To identify phase-regulated genes of H. capsulatum, we carried out expression
      analyses by using a genomic shotgun microarray representing approximately one
      third of the genome, and identified 500 clones that were differentially
      expressed. Genes induced in the mycelial phase included several involved in
      conidiation, cell polarity, and melanin production in other organisms. Genes
      induced in the yeast phase included several involved in sulfur metabolism,
      extending previous observations that sulfur metabolism influences morphology in
      H. capsulatum. Other genes with increased expression in the yeast phase were
      implicated in nutrient acquisition and cell cycle regulation. Unexpectedly,
      differential regulation of the site of transcript initiation was also observed in
      the two phases. These findings identify genes that may determine some of the
      major characteristics of the mycelial and yeast phases.

PMID- 12808033
TI  - Cell and molecular regulation of endothelin-1 production during hepatic wound
      healing.
AB  - During hepatic wound healing, activation of key effectors of the wounding
      response known as stellate cells leads to a multitude of pathological processes,
      including increased production of endothelin-1 (ET-1). This latter process has
      been linked to enhanced expression of endothelin-converting enzyme-1 (ECE-1, the
      enzyme that converts precursor ET-1 to the mature peptide) in activated stellate
      cells. Herein, we demonstrate up-regulation of 56- and 62-kDa ECE-1 3'
      untranslated region (UTR) mRNA binding proteins in stellate cells after liver
      injury and stellate cell activation. Binding of these proteins was localized to a
      CC-rich region in the proximal ECE-1 3' UTR base pairs (the 56-kDa protein) and
      to a region between 60 and 193 base pairs in the ECE-1 3' UTR mRNA (62 kDa). A
      functional role for the 3' UTR mRNA/protein interaction was established in a
      series of reporter assays. Additionally, transforming growth factor-beta1, a
      cytokine integral to wound healing, stimulated ET-1 production. This effect was
      due to ECE-1 mRNA stabilization and increased ECE-1 expression in stellate cells,
      which in turn was a result of de novo synthesis of the identified 56- and 62-kDa
      ECE-1 3' UTR mRNA binding proteins. These data indicate that liver injury and the
      hepatic wound healing response lead to ECE-1 mRNA stabilization in stellate cells
      via binding of 56- and 62-kDa proteins, which in turn are regulated by
      transforming growth factor-beta. The possibility that the same or similar
      regulatory events are present in other forms of wound healing is raised.

PMID- 12808034
TI  - Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial
      outer membrane.
AB  - In Saccharomyces cerevisiae, mitochondrial fusion requires at least two outer
      membrane proteins, Fzo1p and Ugo1p. We provide direct evidence that the dynamin
      related Mgm1 protein is also required for mitochondrial fusion. Like fzo1 and
      ugo1 mutants, cells disrupted for the MGM1 gene contain numerous mitochondrial
      fragments instead of the few long, tubular organelles seen in wild-type cells.
      Fragmentation of mitochondria in mgm1 mutants is rescued by disrupting DNM1, a
      gene required for mitochondrial division. In zygotes formed by mating mgm1
      mutants, mitochondria do not fuse and mix their contents. Introducing mutations
      in the GTPase domain of Mgm1p completely block mitochondrial fusion. Furthermore,
      we show that mgm1 mutants fail to fuse both their mitochondrial outer and inner
      membranes. Electron microscopy demonstrates that although mgm1 mutants display
      aberrant mitochondrial inner membrane cristae, mgm1 dnm1 double mutants restore
      normal inner membrane structures. However, mgm1 dnm1 mutants remain defective in
      mitochondrial fusion, indicating that mitochondrial fusion requires Mgm1p
      regardless of the morphology of mitochondria. Finally, we find that Mgm1p, Fzo1p,
      and Ugo1p physically interact in the mitochondrial outer membrane. Our results
      raise the possibility that Mgm1p regulates fusion of the mitochondrial outer
      membrane through its interactions with Fzo1p and Ugo1p.

PMID- 12808035
TI  - A novel Golgi membrane protein is a partner of the ARF exchange factors Gea1p and
      Gea2p.
AB  - The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are
      highly conserved regulators of membrane dynamics and protein trafficking. The
      interactions of large ARF GEFs with cellular membranes for localization and/or
      activation are likely to participate in regulated recruitment of ARF and
      effectors. However, these interactions remain largely unknown. Here we
      characterize Gmh1p, the first Golgi transmembrane-domain partner of any of the
      high-molecular-weight ARF-GEFs. Gmh1p is an evolutionarily conserved protein. We
      demonstrate molecular interaction between the yeast Gmh1p and the large ARF-GEFs
      Gea1p and Gea2p. This interaction involves a domain of Gea1p and Gea2p that is
      conserved in the eukaryotic orthologues of the Gea proteins. A single mutation in
      a conserved amino acid residue of this domain is sufficient to abrogate the
      interaction, whereas the overexpression of Gmh1p can compensate in vivo defects
      caused by mutations in this domain. We show that Gmh1p is an integral membrane
      protein that localizes to the early Golgi in yeast and in human HeLa cells and
      cycles through the ER. Hence, we propose that Gmh1p acts as a positive Golgi
      membrane partner for Gea function. These results are of general interest given
      the evolutionary conservation of both ARF-GEFs and the Gmh proteins.

PMID- 12808036
TI  - Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.
AB  - S100 proteins are EF hand type Ca2+ binding proteins thought to function in
      stimulus-response coupling by binding to and thereby regulating cellular targets
      in a Ca2+-dependent manner. To isolate such target(s) of the S100P protein we
      devised an affinity chromatography approach that selects for S100 protein ligands
      requiring the biologically active S100 dimer for interaction. Hereby we identify
      ezrin, a membrane/F-actin cross-linking protein, as a dimer-specific S100P
      ligand. S100P-ezrin complex formation is Ca2+ dependent and most likely occurs
      within cells because both proteins colocalize at the plasma membrane after growth
      factor or Ca2+ ionophore stimulation. The S100P binding site is located in the N
      terminal domain of ezrin and is accessible for interaction in dormant ezrin, in
      which binding sites for F-actin and transmembrane proteins are masked through an
      association between the N- and C-terminal domains. Interestingly, S100P binding
      unmasks the F-actin binding site, thereby at least partially activating the ezrin
      molecule. This identifies S100P as a novel activator of ezrin and indicates that
      activation of ezrin's cross-linking function can occur directly in response to
      Ca2+ transients.

PMID- 12808037
TI  - Binding partners for the COOH-terminal appendage domains of the GGAs and gamma
      adaptin.
AB  - The adaptor appendage domains are believed to act as binding platforms for coated
      vesicle accessory proteins. Using glutathione S-transferase pulldowns from pig
      brain cytosol, we find three proteins that can bind to the appendage domains of
      both the AP-1 gamma subunit and the GGAs: gamma-synergin and two novel proteins,
      p56 and p200. p56 elicited better antibodies than p200 and was generally more
      tractable. Although p56 and gamma-synergin bind to both GGA and gamma appendages
      in vitro, immunofluorescence labeling of nocodazole-treated cells shows that p56
      colocalizes with GGAs on TGN46-positive membranes, whereas gamma-synergin
      colocalizes with AP-1 primarily on a different membrane compartment. Furthermore,
      in AP-1-deficient cells, p56 remains membrane-associated whereas gamma-synergin
      becomes cytosolic. Thus, p56 and gamma-synergin show very strong preferences for
      GGAs and AP-1, respectively, in vivo. However, the GGA and gamma appendages share
      the same fold as determined by x-ray crystallography, and mutagenesis reveals
      that the same amino acids contribute to their binding sites. By overexpressing
      wild-type GGA and gamma appendage domains in cells, we can drive p56 and gamma
      synergin, respectively, into the cytosol, suggesting a possible mechanism for
      selectively disrupting the two pathways.

PMID- 12808038
TI  - Distinct developmental function of two Caenorhabditis elegans homologs of the
      cohesin subunit Scc1/Rad21.
AB  - Cohesin, which mediates sister chromatid cohesion, is composed of four subunits,
      named Scc1/Rad21, Scc3, Smc1, and Smc3 in yeast. Caenorhabditis elegans has a
      single homolog for each of Scc3, Smc1, and Smc3, but as many as four for
      Scc1/Rad21 (COH-1, SCC-1/COH-2, COH-3, and REC-8). Except for REC-8 required for
      meiosis, function of these C. elegans proteins remains largely unknown. Herein,
      we examined their possible involvement in mitosis and development. Embryos
      depleted of the homolog of either Scc3, or Smc1, or Smc3 by RNA interference
      revealed a defect in mitotic chromosome segregation but not in chromosome
      condensation and cytokinesis. Depletion of SCC-1/COH-2 caused similar phenotypes.
      SCC-1/COH-2 was present in cells destined to divide. It localized to chromosomes
      in a cell cycle-dependent manner. Worms depleted of COH-1 arrested at either the
      late embryonic or the larval stage, with no indication of mitotic dysfunction.
      COH-1 associated chromosomes throughout the cell cycle in all somatic cells
      undergoing late embryogenesis or larval development. Thus, SCC-1/COH-2 and the
      homologs of Scc3, Smc1, and Smc3 facilitate mitotic chromosome segregation during
      the development, presumably by forming a cohesin complex, whereas COH-1 seems to
      play a role important for development but unrelated to mitosis.

PMID- 12808039
TI  - Golgi localization of Syne-1.
AB  - We have previously identified a Golgi-localized spectrin isoform by using an
      antibody to the beta-subunit of erythrocyte spectrin. In this study, we show that
      a screen of a lambdagt11 expression library resulted in the isolation of an
      approximately 5-kb partial cDNA from a Madin-Darby bovine kidney (MDBK) cell
      line, which encoded a polypeptide of 1697 amino acids with low, but detectable,
      sequence homology to spectrin (37%). A blast search revealed that this clone
      overlaps with the 5' end of a recently identified spectrin family member Syne
      1B/Nesprin-1beta, an alternately transcribed gene with muscle-specific forms that
      bind acetylcholine receptor and associate with the nuclear envelope. By comparing
      the sequence of the MDBK clone with sequence data from the human genome database,
      we have determined that this cDNA represents a central portion of a very large
      gene ( approximately 500 kb), encoding an approximately 25-kb transcript that we
      refer to as Syne-1. Syne-1 encodes a large polypeptide (8406 amino acids) with
      multiple spectrin repeats and a region at its amino terminus with high homology
      to the actin binding domains of conventional spectrins. Golgi localization for
      this spectrin-like protein was demonstrated by expression of epitope-tagged
      fragments in MDBK and COS cells, identifying two distinct Golgi binding sites,
      and by immunofluorescence microscopy by using several different antibody
      preparations. One of the Golgi binding domains on Syne-1 acts as a dominant
      negative inhibitor that alters the structure of the Golgi complex, which
      collapses into a condensed structure near the centrosome in transfected
      epithelial cells. We conclude that the Syne-1 gene is expressed in a variety of
      forms that are multifunctional and are capable of functioning at both the Golgi
      and the nuclear envelope, perhaps linking the two organelles during muscle
      differentiation.

PMID- 12808040
TI  - RNA polymerase III transcripts and the PTB protein are essential for the
      integrity of the perinucleolar compartment.
AB  - The perinucleolar compartment (PNC) is a nuclear substructure present in
      transformed cells. The PNC is defined by high concentrations of certain RNA
      binding proteins and a subset of small RNAs transcribed by RNA polymerase III
      (pol III), including the signal recognition particle RNA and an Alu RNA as
      reported here. To determine if the PNC is dependent on pol III transcription,
      HeLa cells were microinjected with the selective pol III inhibitor, Tagetin. This
      resulted in disassembly of the PNC, whereas inhibition of pol I by cycloheximide
      or pol II by alpha-amanitin did not significantly affect the PNC. However,
      overexpression of one of the PNC-associated RNAs from a pol II promoter followed
      by injection of Tagetin blocked the Tagetin-induced PNC disassembly,
      demonstrating that it is the RNA rather than pol III activity that is important
      for the PNC integrity. To elucidate the role of the PNC-associated protein PTB,
      its synthesis was inhibited by siRNA. This resulted in a reduction of the number
      of PNC-containing cells and the PNC size. Together, these findings suggest, as a
      working model, that PNCs may be involved in the metabolism of specific pol III
      transcripts in the transformed state and that PTB is one of the key elements
      mediating this process.

PMID- 12808041
TI  - Dissociating the centrosomal matrix protein AKAP450 from centrioles impairs
      centriole duplication and cell cycle progression.
AB  - Centrosomes provide docking sites for regulatory molecules involved in the
      control of the cell division cycle. The centrosomal matrix contains several
      proteins, which anchor kinases and phosphatases. The large A-Kinase Anchoring
      Protein AKAP450 is acting as a scaffolding protein for other components of the
      cell signaling machinery. We selectively perturbed the centrosome by modifying
      the cellular localization of AKAP450. We report that the expression in HeLa cells
      of the C terminus of AKAP450, which contains the centrosome-targeting domain of
      AKAP450 but not its coiled-coil domains or binding sites for signaling molecules,
      leads to the displacement of the endogenous centrosomal AKAP450 without removing
      centriolar or pericentrosomal components such as centrin, gamma-tubulin, or
      pericentrin. The centrosomal protein kinase A type II alpha was delocalized. We
      further show that this expression impairs cytokinesis and increases ploidy in
      HeLa cells, whereas it arrests diploid RPE1 fibroblasts in G1, thus further
      establishing a role of the centrosome in the regulation of the cell division
      cycle. Moreover, centriole duplication is interrupted. Our data show that the
      association between centrioles and the centrosomal matrix protein AKAP450 is
      critical for the integrity of the centrosome and for its reproduction.

PMID- 12808042
TI  - Human acyl-coenzyme A:cholesterol acyltransferase expressed in chinese hamster
      ovary cells: membrane topology and active site location.
AB  - Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that
      produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2)
      have been identified. The expression of ACAT1 is ubiquitous, whereas that of
      ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain
      seven transmembrane domains (TMDs). To study ACAT2 topology, we inserted two
      different antigenic tags (hemagglutinin, monoclonal antibody Mab1) at various
      hydrophilic regions flanking each of its predicted TMDs, and expressed the
      recombinant proteins in mutant Chinese hamster ovary cells lacking endogenous
      ACAT. Each tagged ACAT2 was expressed in the endoplasmic reticulum as a single
      undegraded protein band and was at least partially active enzymatically. We then
      used cytoimmunofluorescence and protease protection assays to monitor the
      sidedness of the hemagglutinin and Mab1 tags along the ER membranes. The results
      indicated that ACAT2 contains only two detectable TMDs, located near the N
      terminal region. We also show that a conserved serine (S245), a candidate active
      site residue, is not essential for ACAT catalysis. Instead, a conserved histidine
      (H434) present within a hydrophobic peptide segment, may be essential for ACAT
      catalysis. H434 may be located at the cytoplasmic side of the membrane.

PMID- 12808043
TI  - The fission yeast meiotic regulator Mei2p forms a dot structure in the horse-tail
      nucleus in association with the sme2 locus on chromosome II.
AB  - Fission yeast Mei2p is an RNA-binding protein essential for induction of both
      premeiotic DNA synthesis and first meiotic division. Mei2p forms a dot structure
      at an apparently fixed position in the horse-tail nucleus during meiotic
      prophase. This dot formation requires a meiosis-specific RNA species, meiRNA,
      which is indispensable for meiosis I, and the emergence of the dot is an
      indicator of the ability of the cell to perform meiosis I. Herein, we have sought
      the identity of this dot. Analyses using chromosome segregation in haploid
      meiosis, reciprocal translocation of chromosomes, and gene translocation have led
      us to conclude that the Mei2p dot is in association with the sme2 gene on the
      short arm of chromosome II, which encodes meiRNA. Transcripts of sme2, rather
      than the DNA sequence of the gene, seem to be the determinant of the localization
      of the Mei2p dot. However, evidence suggests that the dot may not be a simple
      reflection of the attachment of Mei2p to meiRNA undergoing transcription. We
      speculate that the Mei2p dot is a specialized structure, either to foster the
      assembly of Mei2p and meiRNA or to perform some unidentified function
      indispensable for meiosis I.

PMID- 12808044
TI  - Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1
      (ZO-1).
AB  - Connexin alpha1Cx43 has previously been shown to bind to the PDZ domain
      containing protein ZO-1. The similarity of the carboxyl termini of this connexin
      and the lens fiber connexins alpha3Cx46 and alpha8Cx50 suggested that these
      connexins may also interact with ZO-1. ZO-1 was shown to be highly expressed in
      mouse lenses. Colocalization of ZO-1 with alpha3Cx46 and alpha8Cx50 connexins in
      fiber cells was demonstrated by immunofluorescence and by fracture-labeling
      electron microscopy but showed regional variations throughout the lens. ZO-1 was
      found to coimmunoprecipitate with alpha3Cx46 and alpha8Cx50, and pull-down
      experiments showed that the second PDZ domain of ZO-1 was involved in this
      interaction. Transiently expressed alpha3Cx46 and alpha8Cx50 connexins lacking
      the COOH-terminal residues did not bind to the second PDZ domain but still formed
      structures resembling gap junctions by immunofluorescence. These results indicate
      that ZO-1 interacts with lens fiber connexins alpha3Cx46 and alpha8Cx50 in a
      manner similar to that previously described for alpha1Cx43. The spatial variation
      in the interaction of ZO-1 with lens gap junctions is intriguing and is
      suggestive of multiple dynamic roles for this association.

PMID- 12808045
TI  - Calponin repeats regulate actin filament stability and formation of podosomes in
      smooth muscle cells.
AB  - Phorbol ester induces actin cytoskeleton rearrangements in cultured vascular
      smooth muscle cells. Calponin and SM22 alpha are major components of
      differentiated smooth muscle and potential regulators of actin cytoskeleton
      interactions. Here we show that actin fibers decorated with h1 CaP remain stable,
      whereas SM22 alpha-decorated actin bundles undergo rapid reorganization into
      podosomes within 30 min of PDBu exposure. Ectopic expression of GFP alpha-actinin
      had no effect on the stability of the actin cytoskeleton and alpha-actinin was
      transported rapidly into PDBu-induced podosomes. Our results demonstrate the
      involvement of CaP and SM22 alpha in coordinating the balance between
      stabilization and dynamics of the actin cytoskeleton in mammalian smooth muscle.
      We provide evidence for the existence of two functionally distinct actin filament
      populations and introduce a molecular mechanism for the stabilization of the
      actin cytoskeleton by the unique actin-binding interface formed by calponin
      family-specific CLIK23 repeats.

PMID- 12808046
TI  - Caenorhabditis elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of
      UNC-97/PINCH in muscle adhesion complexes.
AB  - To further understand the assembly and maintenance of the muscle contractile
      apparatus, we have identified a new protein, UNC-98, in the muscle of
      Caenorhabditis elegans. unc-98 mutants display reduced motility and a
      characteristic defect in muscle structure. We show that the major defect in the
      mutant muscle is in the M-lines and dense bodies (Z-line analogs). Both
      functionally and compositionally, nematode M-lines and dense bodies are analogous
      to focal adhesions of nonmuscle cells. UNC-98 is a novel 310-residue polypeptide
      consisting of four C2H2 Zn fingers and several possible nuclear localization
      signal and nuclear export signal sequences. By use of UNC-98 antibodies and green
      fluorescent protein fusions (to full-length UNC-98 and UNC-98 fragments), we have
      shown that UNC-98 resides at M-lines, muscle cell nuclei, and possibly at dense
      bodies. Furthermore, we demonstrated that 1) the N-terminal 106 amino acids are
      both necessary and sufficient for nuclear localization, and 2) the C-terminal
      (fourth) Zn finger is required for localization to M-lines and dense bodies. UNC
      98 interacts with UNC-97, a C. elegans homolog of PINCH. We propose that UNC-98
      is both a structural component of muscle focal adhesions and a nuclear protein
      that influences gene expression.

PMID- 12808047
TI  - Alpha-smooth muscle actin is crucial for focal adhesion maturation in
      myofibroblasts.
AB  - Cultured myofibroblasts are characterized by stress fibers, containing alpha
      smooth muscle actin (alpha-SMA) and by supermature focal adhesions (FAs), which
      are larger than FAs of alpha-SMA-negative fibroblasts. We have investigated the
      role of alpha-SMA for myofibroblast adhesion and FA maturation. Inverted
      centrifugation reveals two phases of initial myofibroblast attachment: during the
      first 2 h of plating microfilament bundles contain essentially cytoplasmic actin
      and myofibroblast adhesion is similar to that of alpha-SMA-negative fibroblasts.
      Then, myofibroblasts incorporate alpha-SMA in stress fibers, develop mature FAs
      and their adhesion capacity is significantly increased. When alpha-SMA expression
      is induced in 5 d culture by TGFbeta or low serum levels, fibroblast adhesion is
      further increased correlating with a "supermaturation" of FAs. Treatment of
      myofibroblasts with alpha-SMA fusion peptide (SMA-FP), which inhibits alpha-SMA
      mediated contractile activity, reduces their adhesion to the level of alpha-SMA
      negative fibroblasts. With the use of flexible micropatterned substrates and EGFP
      constructs we show that SMA-FP application leads to a decrease of myofibroblast
      contraction, shortly followed by disassembly of paxillin- and beta3 integrin
      containing FAs; alpha5 integrin distribution is not affected. FRAP of beta3
      integrin-EGFP demonstrates an increase of FA protein turnover following SMA-FP
      treatment. We conclude that the formation and stability of supermature FAs
      depends on a high alpha-SMA-mediated contractile activity of myofibroblast stress
      fibers.

PMID- 12808048
TI  - The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions
      and dephosphorylates beta-catenin.
AB  - Cell-cell adhesion regulates processes important in embryonal development, normal
      physiology, and cancer progression. It is regulated by various mechanisms
      including tyrosine phosphorylation. We have previously shown that the protein
      tyrosine phosphatase Pez is concentrated at intercellular junctions in confluent,
      quiescent monolayers but is nuclear in cells lacking cell-cell contacts. We show
      here with an epithelial cell model that Pez localizes to the adherens junctions
      in confluent monolayers. A truncation mutant lacking the catalytic domain acts as
      a dominant negative mutant to upregulate tyrosine phosphorylation at adherens
      junctions. We identified beta-catenin, a component of adherens junctions, as a
      substrate of Pez by a "substrate trapping" approach and by in vitro
      dephosphorylation with recombinant Pez. Consistent with this, ectopic expression
      of the dominant negative mutant caused an increase in tyrosine phosphorylation of
      beta-catenin, demonstrating that Pez regulates the level of tyrosine
      phosphorylation of adherens junction proteins, including beta-catenin. Increased
      tyrosine phosphorylation of adherens junction proteins has been shown to decrease
      cell-cell adhesion, promoting cell migration as a result. Accordingly, the
      dominant negative Pez mutant enhanced cell motility in an in vitro "wound" assay.
      This suggests that Pez is also a regulator of cell motility, most likely through
      its action on cell-cell adhesion.

PMID- 12808049
TI  - The Chlamydomonas Fus1 protein is present on the mating type plus fusion
      organelle and required for a critical membrane adhesion event during fusion with
      minus gametes.
AB  - The molecular mechanisms of the defining event in fertilization, gamete fusion,
      remain poorly understood. The FUS1 gene in the unicellular, biflagellated green
      alga Chlamydomonas is one of the few sex-specific eukaryotic genes shown by
      genetic analysis to be essential for gamete fusion during fertilization. In
      Chlamydomonas, adhesion and fusion of the plasma membranes of activated mt+ and
      mt- gametes is accomplished via specialized fusion organelles called mating
      structures. Herein, we identify the endogenous Fus1 protein, test the idea that
      Fus1 is at the site of fusion, and identify the step in fusion that requires
      Fus1. Our results show that Fus1 is a approximately 95-kDa protein present on the
      external surface of both unactivated and activated mt+ gametes. Bioassays
      indicate that adhesion between mating type plus and mating type minus fusion
      organelles requires Fus1 and that Fus1 is functional only after gamete
      activation. Finally, immunofluorescence demonstrates that the Fus1 protein is
      present as an apical patch on unactivated gametes and redistributes during gamete
      activation over the entire surface of the microvillous-like activated plus mating
      structure, the fertilization tubule. Thus, Fus1 is present on mt+ gametes at the
      site of cell-cell fusion and essential for an early step in the fusion process.

PMID- 12808050
TI  - Nuclear export and plasma membrane recruitment of the Ste5 scaffold are
      coordinated with oligomerization and association with signal transduction
      components.
AB  - The Ste5 scaffold activates an associated mitogen-activated protein kinase
      cascade by binding through its RING-H2 domain to a Gbetagamma dimer (Ste4/Ste18)
      at the plasma membrane in a recruitment event that requires prior nuclear
      shuttling of Ste5. Genetic evidence suggests that Ste5 must oligomerize to
      function, but its impact on Ste5 function and localization is unknown. Herein, we
      show that oligomerization affects Ste5 activity and localization. The majority of
      Ste5 is monomeric, suggesting that oligomerization is tightly regulated.
      Increasing the pool of Ste5 oligomers increases association with Ste11.
      Remarkably, Ste5 oligomers are also more efficiently exported from the nucleus,
      retained in the cytoplasm by Ste11 and better recruited to the plasma membrane,
      resulting in constitutive activation of the mating mitogen-activated protein
      kinase cascade. Coprecipitation tests show that the RING-H2 domain is the key
      determinant of oligomerization. Mutational analysis suggests that the leucine
      rich domain limits the accessibility of the RING-H2 domain and inhibits export
      and recruitment in addition to promoting Ste11 association and activation. Our
      results suggest that the major form of Ste5 is an inactive monomer with an
      inaccessible RING-H2 domain and Ste11 binding site, whereas the active form is an
      oligomer that is more efficiently exported and recruited and has a more
      accessible RING-H2 domain and Ste11 binding site.

PMID- 12808051
TI  - Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to
      accumulation of unfolded proteins.
AB  - In the unfolded protein response (UPR) signaling pathway, accumulation of
      unfolded proteins in the endoplasmic reticulum (ER) activates a transmembrane
      kinase/ribonuclease Ire1, which causes the transcriptional induction of ER
      resident chaperones, including BiP/Kar2. It was previously hypothesized that
      BiP/Kar2 plays a direct role in the signaling mechanism. In this model,
      association of BiP/Kar2 with Ire1 represses the UPR pathway while under
      conditions of ER stress, BiP/Kar2 dissociation leads to activation. To test this
      model, we analyzed five temperature-sensitive alleles of the yeast KAR2 gene.
      When cells carrying a mutation in the Kar2 substrate-binding domain were
      incubated at the restrictive temperature, association of Kar2 to Ire1 was
      disrupted, and the UPR pathway was activated even in the absence of extrinsic ER
      stress. Conversely, cells carrying a mutation in the Kar2 ATPase domain, in which
      Kar2 poorly dissociated from Ire1 even in the presence of tunicamycin, a potent
      inducer of ER stress, were unable to activate the pathway. Our findings provide
      strong evidence in support of BiP/Kar2-dependent Ire1 regulation model and
      suggest that Ire1 associates with Kar2 as a chaperone substrate. We speculate
      that recognition of unfolded proteins is based on their competition with Ire1 for
      binding with BiP/Kar2.

PMID- 12808052
TI  - The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced
      adhesion and migration.
AB  - Rap1 is a potent inside-out signal that increases LFA-1 adhesive activity. In
      this study, we have defined the cytoplasmic region of the alphaL and beta2
      integrin that are required for Rap1-stimulated adhesion and subsequent migration
      on ICAM-1. Human LFA-1 bearing truncated and point-mutated alphaL and beta2
      cytoplasmic regions were reconstituted in mouse IL-3-dependent proB cells, BAF/3.
      Truncation of the alphaL, but not beta2 subunit cytoplasmic region, abolished
      Rap1V12-dependent adhesion to ICAM-1. The alanine substitution of two lysine
      residues (K1097/K1099) in the alphaL subunit was found to be critical in adhesion
      induced by Rap1V12, but not PMA. This mutation suppressed Rap1V12-induced LFA-1
      conformation changes and ligand-binding affinity. The K1097/K1099 mutation also
      impaired binding to ICAM-1 induced by TCR cross-linking or SDF-1. In contrast,
      the alanine substitution for tyrosine in the beta2 subunit endocytosis motif
      inhibited internalization of LFA-1, and severely impaired detachment at the cell
      rear, which resulted in long-elongated cell shapes. This result demonstrates that
      internalization of LFA-1 is a critical step in the deadhesion process. Our study
      revealed novel requirements of amino acid residues of the LFA-1 cytoplasmic
      region in the response to the inside-out signaling and the subsequent deadhesion
      process.

PMID- 12808053
TI  - Biphasic estradiol-induced AKT phosphorylation is modulated by PTEN via MAP
      kinase in HepG2 cells.
AB  - We reported previously in HepG2 cells that estradiol induces cell cycle
      progression throughout the G1-S transition by the parallel stimulation of both
      PKC-alpha and ERK signaling molecules. The analysis of the cyclin D1 gene
      expression showed that only the MAP kinase pathway was involved. Here, the
      presence of rapid/nongenomic, estradiol-regulated, PI3K/AKT signal transduction
      pathway, its modulation by the levels of the tumor suppressor PTEN, its cross
      talk with the ERK pathway, and its involvement in DNA synthesis and cyclin D1
      gene promoter activity have all been studied in HepG2 cells. 17beta-Estradiol
      induced the rapid and biphasic phosphorylation of AKT. These phosphorylations
      were independent of each other, being the first wave of activation independent of
      the estrogen receptor (ER), whereas the second was dependent on ER. Both
      activations were dependent on PI3K activity; furthermore, the ERK pathway
      modulated AKT phosphorylation by acting on the PTEN levels. The results showed
      that the PI3K pathway, as well as ER, were strongly involved in both G1-S
      progression and cyclin D1 promoter activity by acting on its proximal region (
      254 base pairs). These data indicate that in HepG2 cells, different
      rapid/nongenomic estradiol-induced signal transduction pathways modulate the
      multiple steps of G1-S phase transition.

PMID- 12808054
TI  - The C-terminal extension of a hybrid immunoglobulin A/G heavy chain is
      responsible for its Golgi-mediated sorting to the vacuole.
AB  - We have assessed the ability of the plant secretory pathway to handle the
      expression of complex heterologous proteins by investigating the fate of a hybrid
      immunoglobulin A/G in tobacco cells. Although plant cells can express large
      amounts of the antibody, a relevant proportion is normally lost to vacuolar
      sorting and degradation. Here we show that the synthesis of high amounts of IgA/G
      does not impose stress on the plant secretory pathway. Plant cells can assemble
      antibody chains with high efficiency and vacuolar transport occurs only after the
      assembled immunoglobulins have traveled through the Golgi complex. We prove that
      vacuolar delivery of IgA/G depends on the presence of a cryptic sorting signal in
      the tailpiece of the IgA/G heavy chain. We also show that unassembled light
      chains are efficiently secreted as monomers by the plant secretory pathway.

PMID- 12808056
TI  - Ki-67 and p53 expression in minimal deviation melanomas as compared with other
      nevomelanocytic lesions.
AB  - Minimal deviation melanoma is a controversial entity encompassing a heterogeneous
      group of lesions cytologically in the spectrum between recognized subtypes of
      nevi and conventional "primary configuration" melanomas and reported to have a
      better prognosis than the latter. To evaluate the distinctiveness of minimal
      deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal
      deviation melanomas were compared with those in compound nevi, Spitz nevi, and
      vertical growth phase superficial spreading malignant melanoma. Twelve examples
      of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins
      and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67
      (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation
      melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and
      25%, respectively. The mean Ki-67 proliferation rate was statistically greater in
      the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P
      <.05), but the proliferation rates in the two melanoma subtypes were not
      statistically significant (P =.08). The mean p53 values for these lesions were 0,
      9%, 9%, and 26%, respectively; the latter two were statistically different (P
      <.01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma
      may represent a distinct entity.

PMID- 12808055
TI  - Regulation of PRAK subcellular location by p38 MAP kinases.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role
      in cellular responses to inflammatory stimuli and environmental stress. p38
      regulated/activated protein kinase (PRAK, also known as mitogen-activated protein
      kinase activated protein kinase 5 [MAPKAPK5]) functions downstream of p38alpha
      and p38beta in mediating the signaling of the p38 pathway. Immunostaining
      revealed that endogenous PRAK was predominantly localized in the cytoplasm.
      Interestingly, ectopically expressed PRAK was localized in the nucleus and can be
      redistributed by coexpression of p38alpha or p38beta to the locations of p38alpha
      and p38beta. Mutations in the docking groove on p38alpha/p38beta, or the p38
      docking site in PRAK, disrupted the PRAK-p38 interaction and impaired the ability
      of p38alpha and p38beta to redistribute ectopically expressed PRAK, indicating
      that the location of PRAK could be controlled by its docking interaction with
      p38alpha and p38beta. Although the majority of PRAK molecules were detected in
      the cytoplasm, PRAK is consistently shuttling between the cytoplasm and the
      nucleus. A sequence analysis of PRAK shows that PRAK contains both a putative
      nuclear export sequence (NES) and a nuclear localization sequence (NLS). The
      shuttling of PRAK requires NES and NLS motifs in PRAK and can be regulated
      through cellular activation induced by stress stimuli. The nuclear content of
      PRAK was reduced after stimulation, which resulted from a decrease in the nuclear
      import of PRAK and an increase in the nuclear export of PRAK. The nuclear import
      of PRAK is independent from p38 activation, but the nuclear export requires p38
      mediated phosphorylation of PRAK. Thus, the subcellular distribution of PRAK is
      determined by multiple factors including its own NES and NLS, docking
      interactions between PRAK and docking proteins, phosphorylation of PRAK, and
      cellular activation status. The p38 MAPKs not only regulate PRAK activity and
      PRAK activation-related translocation, but also dock PRAK to selected subcellular
      locations in resting cells.

PMID- 12808057
TI  - Adenomyoma and adenomyomatous hyperplasia of the Vaterian system: clinical,
      pathological, and new immunohistochemical features of 13 cases.
AB  - Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are consistently
      benign lesions. Clinically, adenomyoma mimics frequently ampullary adenoma or
      carcinoma, and biopsy analysis is often difficult. The histogenesis of ampullary
      adenomyoma and adenomyomatous hyperplasia is still subject to debate. We present
      a retrospective study of clinicopathological features of 13 cases of surgically
      resected ampullary adenomyoma. The age of our patients was between 38 and 78
      years (mean: 63 y). The preoperative diagnosis was ampullary tumor or tumor of
      the head of the pancreas. On macroscopy, a white, firm lesion of the ampullary
      wall was observed; its size ranged between 10 and 30 mm. Histologically the
      lesion consisted of multiple glandular structures surrounded by a
      fibroblastic/myofibroblastic proliferation, resulting in a "pseudo-hypertrophy"
      of the Vaterian system. The immunophenotype of the epithelial component was
      cytokeratin 7+/cytokeratin 20-, similar to that of the normal biliary and
      pancreatic duct system. The epithelial cells exhibited low proliferative
      activity. The hyperplastic myofibroblastic cells expressed smooth muscle actin. A
      complete pancreatic heterotopy contiguous with the adenomyoma was noted in three
      cases. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are
      benign lesions frequently treated by extensive surgery because of long-term
      biliary obstruction. The clinicopathological characteristics suggest either a
      reactive and/or a malformative, nonneoplastic nature for this lesion, which
      could, in some cases, develop from heterotopic pancreas. The immunophenotype of
      epithelial cells may be a useful tool for differentiating it from ampullary
      adenoma on biopsy specimens.

PMID- 12808058
TI  - Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary
      mucinous carcinomas are usually microsatellite stable.
AB  - Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual
      ductal adenocarcinomas in their mucin expression profile and share with many
      extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous
      carcinomas are frequently associated with mutations of the DNA mismatch repair
      genes, causing them to exhibit the so-called mutator phenotype, we decided to
      investigate whether MNCCs of the pancreas are characterized by microsatellite
      instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous
      noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an
      invasive muconodular component, and 1 ductal adenocarcinoma with an extensive
      mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained
      with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and
      hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five
      primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were
      analyzed. MSI was diagnosed in case a novel allele was found, compared with the
      normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas
      tested exhibited nuclear expression of mismatch repair gene products, except for
      one MNCC that also showed MSI at the molecular level. The data suggest that
      pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1-) do not appear to
      normally exhibit mutations in the mismatch repair genes and therefore differ in
      their carcinogenesis from those in other organs.

PMID- 12808059
TI  - Galectin-1-mediated apoptosis in mycosis fungoides: the roles of CD7 and cell
      surface glycosylation.
AB  - Sezary cells, the malignant T cells in mycosis fungoides/Sezary syndrome, resist
      a variety of apoptosis-inducing agents, a feature that contributes to the poor
      response to therapy in mycosis fungoides. Galectin-1 is a mammalian lectin that
      triggers T cell apoptosis. For T cells to be susceptible to galectin-1-induced
      apoptosis, the T cells must express specific glycoprotein receptors, such as CD7,
      that bear the specific oligosaccharides recognized by galectin-1. Because Sezary
      cells are characteristically CD7(-), lack of CD7 expression has been proposed to
      render Sezary cells resistant to galectin-1-induced death. However, the role
      played by aberrant cell surface glycosylation in resistance of Sezary cells to
      galectin-1 has not been examined. In this study, we demonstrated abundant
      galectin-1 in mycosis fungoides skin lesions, indicating that Sezary cells are
      exposed to galectin-1 in vivo. To determine specific characteristics of Sezary
      cells that contribute to galectin-1 resistance, we assessed CD7 expression and
      cell surface glycosylation of Sezary cells in mycosis fungoides lesions and of
      four Sezary T cell lines. Sezary cells in primary lesions and Sezary T cell lines
      demonstrated a characteristic "glycotype" with sialylated core 1 O-glycans that
      promote galectin-1 resistance. Expression of CD7 was necessary but not sufficient
      for galectin-1-induced death of Sezary cell lines. In addition, CD7(-) Sezary
      cell lines, and Sezary cells within mycosis fungoides lesions, expressed galectin
      1, whereas CD7-positive Sezary cell lines did not express galectin-1. We propose
      that both loss of CD7 expression and altered cellular glycosylation contribute to
      apoptosis resistance of malignant T cells in mycosis fungoides.

PMID- 12808060
TI  - Overexpression of VEGF and angiopoietin 2: a key to high vascularity of
      hepatocellular carcinoma?
AB  - Hepatocellular carcinoma (HCC) is becoming one of the most common malignant
      tumors worldwide and is characterized by a high vascularity. Angiogenesis,
      formation of new microvessels, is critical for the growth and progression of
      various human solid tumors. Vascular endothelial growth factor (VEGF) and
      angiopoietins (Ang1 and Ang2) are endothelial cell-specific vasculogenic and
      angiogenic growth factors, but their expression and roles in HCC have not been
      extensively explored. The aim of this study was to determine the expression and
      cellular localization of VEGF, Ang1, and Ang2 in specimens of resected human HCC
      using in situ hybridization and immunohistochemical staining and to examine their
      relationship to microvessel density (MVD) and tumor size. We also investigated
      whether mutation of p53 protein might affect the expression of the above
      angiogenic growth factors. VEGF and Ang2 were strongly expressed and localized
      predominantly to cancer cells, whereas Ang1 was detected in supportive cells of
      large blood vessels, stromal cells, endothelial cells, and tumor cells.
      Expression of the VEGF protein and the Ang2 (but not Ang1) mRNA were strongly
      correlated with MVD (P <.05, P =.001) and tumor size (P <.05). There was also a
      strong correlation between VEGF protein and Ang2 mRNA expression (P <.001).
      However, no significant correlation was found between overexpression of p53 and
      the expression of VEGF, angiopoietins, or MVD. These findings suggest that
      overproduction of the angiogenic growth factors VEGF and Ang2 by HCC cells may
      increase vascularity and tumor growth in a paracrine manner. Our findings also
      suggest that interaction between VEGF and Ang2 may play a critical role in tumor
      angiogenesis in HCC.

PMID- 12808061
TI  - Prognostic significance of glutathione S-transferase-pi in invasive breast
      cancer.
AB  - Glutathione S-transferase pi (GST-pi), a Phase II detoxification enzyme, has
      recently been implicated in protection against apoptosis. Expression of GST-pi
      and Bcl-2 protein, an established apoptosis marker, was analyzed by
      immunohistochemistry in 116 cases of infiltrative ductal breast carcinomas in
      Singapore women. The markers were correlated with apoptosis detected by the TUNEL
      method and clinico-pathological parameters. There were 67 (58%) GST-pi-positive
      breast tumors and 43 (37%) Bcl-2-positive tumors. In a large proportion of GST-pi
      positive/Bcl-2-positive tumors, there was a distinct accumulation of the GST-pi
      enzyme within the nucleus of cancer cells when examined by double
      immunofluorescence labeling under confocal microscopy. GST-pi immunoreactivity
      was not significantly correlated with any of the traditional histologic factors
      known to influence prognosis, whereas Bcl-2 overexpression was associated with
      reduced size of primary tumor (P =.021) and positive estrogen receptor status (P
      =.001). Univariate analysis revealed that GST-pi-positive, Bcl-2-positive, and
      lower histological grade tumors had decreased levels of apoptosis (P =.024, P
      =.011, and P =.029, respectively). However, multivariate analysis showed that
      histological grade and Bcl-2, but not GST-pi, immunoreactivity were correlated
      with apoptotic status. The Kaplan-Meier disease-free survival curves showed a
      significant difference between GST-pi-positive and GST-pi-negative breast cancer
      cases (P =.002). Disease-free survival in patients with GST-pi-positive tumors
      was also worse than that in patients with GST-pi-negative tumors in the group who
      had adjuvant chemotherapy (P =.04). In patients who were lymph node positive, GST
      pi immunopositivity was found to influence disease-free survival. Recurrence of
      tumors was also significantly affected by GST-pi immunoreactivity (relative risk
      of 8.1). The findings indicate that GST-pi-positive tumors are more aggressive
      and have a poorer prognosis than do corresponding GST-pi-negative breast cancers.

PMID- 12808062
TI  - Longer failure-free survival interval of Epstein-Barr virus-associated classical
      Hodgkin's lymphoma: a single-institution study.
AB  - We analyzed Epstein-Barr virus association in classical Hodgkin's lymphoma from a
      single center in Austria with special emphasis on the latent membrane protein1
      gene configuration and clinical outcome. All 119 (65 male, 54 female) patients
      were treated from 1974 to 1999 in the Division of Hematology and Oncology at the
      Department of Internal Medicine, University of Innsbruck, Austria. The mean
      follow-up time was 122 months (range, 3-333 mo). Epstein-Barr virus was examined
      by latent membrane protein1 immunohistochemistry and by in situ hybridization for
      Epstein-Barr virus-encoded early ribonuclein acid transcripts. For assessment of
      the Epstein-Barr virus subtype (A/B) and latent membrane protein1 gene
      configuration, the polymerase chain reaction was employed. Fifty-four reactive
      tonsils were used as the control population. These results as well as clinical
      parameters such as age, gender, tumor stage, risk factors, and B symptoms were
      correlated with failure-free and overall survival. Latent membrane protein1 was
      detected in 31/119 (26%) classical Hodgkin's lymphoma, and Epstein-Barr virus
      subtyping was successful in 19 of the 31 virus-infected classical Hodgkin's
      lymphoma cases, as well as in 28 of 54 reactive tonsils. Subtype A was observed
      in all classical Hodgkin's lymphoma patients and in 26/28 (93%) tonsils. The 30
      base pair latent membrane protein1 gene deletion was found in only 4/31 (13%)
      Epstein-Barr virus-associated classical Hodgkin's lymphoma as well as in 20/54
      (37%) reactive tonsils. Patients with Epstein-Barr virus-associated classical
      Hodgkin's lymphoma showed a significantly longer mean time to first relapse of 99
      months, as compared with 49 months for the Epstein-Barr virus-negative cases (P
      <.02), and were more frequent in those aged >45 years (P <.04). Epstein-Barr
      virus-associated classical Hodgkin's lymphoma were predominantly of the mixed
      cellularity subtype and occurred more frequently in male patients, in patients
      with Stage III and IV, and in patients with B symptoms as well as risk factors.
      However, overall survival did not correlate with Epstein-Barr virus association.
      The 30-base pair latent membrane protein1 gene deletion had no influence on
      overall survival and failure-free survival time. Although the number of patients
      with this specific mutation was low, it further shows that an increased oncogenic
      potential of the latent membrane protein1 deletion variant is unlikely. This
      large single-center study demonstrates a low prevalence of Epstein-Barr virus
      positivity in classical Hodgkin's lymphoma in western Europe. In accordance with
      results of similar studies, the presence of Epstein-Barr virus has a beneficial
      effect on the length of failure-free survival despite the higher frequency of
      risk factors such as higher tumor stage or advanced age.

PMID- 12808063
TI  - Survivin expression in ovarian carcinoma: correlation with apoptotic markers and
      prognosis.
AB  - Survivin is a novel inhibitor of apoptosis commonly detected in tissues during
      fetal development and in cancer, but not usually in normal tissues. Expression of
      this protein may be of prognostic significance and therapeutically relevant in
      many cancers. We assessed survivin expression in ovarian carcinoma, correlating
      results with expression of other anti-apoptotic (bcl-2, bcl-x, mutant p53) and
      pro-apoptotic (bax) markers, with prognostic parameters, and prognosis. Paraffin
      embedded sections of 49 ovarian carcinoma were immunostained for survivin, bcl-2,
      bcl-x, bax, and p53. Expression was evaluated in nuclei and cytoplasm, as
      intensity (0-3+), and percentage of positive cells was scored on a four-tiered
      system with <10% as negative. Frequency of survivin, bcl-2, bcl-x, bax, and p53
      was 73.5%, 36.7%, 93.9%, 77.6%, and 60.4%, respectively. There was significant
      correlation between nuclear survivin expression and grade (P =.0014), histologic
      type (P =.0376), and mutant p53 (P =.0414). Survivin expression did not correlate
      with bcl-2, bcl-x, or bax expression, stage, or overall or disease-free survival.
      The majority (74%) of ovarian carcinoma show survivin expression, which
      correlates with poor prognostic parameters (high grade, histologic type, p53
      mutation) but not with survival. Therapeutic targeting of survivin in ovarian
      carcinoma is a future possibility.

PMID- 12808064
TI  - Ovarian sex cord-stromal tumors: an immunohistochemical study including a
      comparison of calretinin and inhibin.
AB  - Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous
      neoplasms that are relatively infrequently encountered, their diagnosis can be
      difficult. Immunohistochemical staining may be useful for establishing the
      diagnosis in problematic cases. We studied 53 ovarian SCSTs to characterize their
      immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4
      juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules
      (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas
      (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a
      metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin
      cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The
      fibromas and FTs were also tested with CD10. The extent of staining was assessed
      in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the
      tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of
      the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs
      were negative. WT1 was present in 39 tumors (74%), with expression most prominent
      in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas
      just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for
      CK5/6, and the 15 fibromas and FTs were negative for CD10. We conclude that
      because cytokeratin is frequently expressed by SCSTs, in particular by granulosa
      cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to
      exclude epithelial neoplasms. In addition, WT1, present in normal granulosa
      cells, is expressed by a majority of SCSTs. Finally, these results demonstrate
      that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and
      that it is more sensitive than inhibin for fibromas and FTs.

PMID- 12808065
TI  - The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating
      adrenal cortical and medullary tumors: an immunohistochemical study.
AB  - Morphologic distinction between adrenal cortical and medullary tumors can be
      difficult. Previous studies have shown inhibin, melan-A, and BCL-2 to be useful
      markers for adrenal cortical tumors. We have recently observed a high level of
      calretinin expression in normal adrenal cortex but not the medulla and therefore
      evaluated its diagnostic application for adrenal tumors in comparison with
      inhibin, melan-A, and BCL-2. C-kit is a transmembrane tyrosine kinase receptor.
      Immunodetection of c-kit expression has been recently used for tumor diagnosis,
      and c-kit-positive tumors can potentially benefit from kit kinase inhibitor
      treatment. Although c-kit expression was reported in adrenal medulla and
      pheochromocytoma, it has not been evaluated in adrenal cortical tumors. In this
      study, 28 adrenal cortical tumors (12 carcinomas, 16 adenomas), 20
      pheochromocytomas, and 20 extraadrenal paragangliomas were evaluated for
      calretinin, inhibin, melan-A, BCL-2, and c-kit expression by standard
      immunohistochemical assays on paraffin sections. The percentage of
      immunoreactivity in adrenal cortical tumors was as follows: calretinin, 96%;
      melan-A, 89%; inhibin, 92%; BCL-2, 20%; and c-kit, 5%. Normal adrenal medulla did
      not stain for c-kit but was positive for BCL-2. Eighty-six percent of
      pheochromocytomas stained for BCL-2 and none for calretinin, with the exception
      of the ganglioneuromatous areas in composite pheochromocytomas (n = 5).
      Extraadrenal paragangliomas showed reactivity with calretinin in 25%, melan-A in
      5%, inhibin in 16%, BCL-2 in 38%, and c-kit in 8% of the cases. Our results
      indicate that calretinin is the most sensitive among all the adrenal markers
      tested. Like melan-A and inhibin, calretinin is also a very specific marker in
      differentiating cortical from medullary adrenal tumors. In addition, calretinin
      can be used to confirm a composite pheochromocytoma. BCL-2 does not appear to be
      useful in differentiating adrenal cortical from medullary tumors. C-kit is not
      useful in the diagnosis of adrenal tumors, and kit kinase inhibitor might have a
      limited role in the treatment of adrenal tumors and paraganglioma because of the
      low frequency of c-kit expression in these tumors.

PMID- 12808066
TI  - Basal cell hyperplasia in the peripheral zone of the prostate.
AB  - Basal cell hyperplasia in the prostate is often viewed as a transition zone
      proliferation, related to usual, nodular glandular, and stromal hyperplasia.
      Basal cell hyperplasia in the prostatic peripheral zone, the most common site for
      development of prostatic intraepithelial neoplasia and carcinoma, has not been
      previously characterized. We characterized the incidence and histomorphological
      attributes of basal cell hyperplasia in a series of 500 consecutive sextant
      needle core biopsy samples and in 26 completely embedded prostate glands from
      radical prostatectomy specimens. Comparative proliferation indices (by MIB-1
      staining) and apoptotic indices (by TUNEL labeling) were quantitated for
      peripheral zone versus transition zone basal cell hyperplasia versus normal basal
      cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue
      was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of
      the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of
      cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and
      associated with inflammation, which was usually lymphocytic, in 84% of cases.
      Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands.
      Peripheral zone basal cell hyperplasia was not observed to be in direct physical
      continuity with intraepithelial or invasive neoplasia. Peripheral zone and
      transition zone basal cell hyperplasia exhibited similar mean proliferation and
      apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was
      elevated, and apoptotic index was decreased, relative to normal basal cells (P =
      1 x 10(-7)). Basal cell hyperplasia in the peripheral zone is present in a
      significant minority of prostate needle biopsy samples and whole prostate glands.
      The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic
      concern for a neoplastic proliferation. The increase in cell number in basal cell
      hyperplasia appears to be due to a coordinate increase in proliferation index
      coupled with a diminished apoptotic index. The presence of inflammation in the
      majority of basal cell hyperplasia foci suggests that peripheral zone basal cell
      hyperplasia in untreated patients may represent a stereotyped response to injury
      such as that sustained because of inflammation.

PMID- 12808067
TI  - Analysis of the PI-3-Kinase-PTEN-AKT pathway in human lymphoma and leukemia using
      a cell line microarray.
AB  - Tissue microarray technology facilitates rapid assessment of expression of
      molecular markers by enabling the simultaneous analysis of hundreds of tissue
      specimens. We have applied this technology to establish a microarray composed of
      cell pellets derived from 40 human lymphoma/leukemia-derived cell lines harboring
      a variety of molecular abnormalities. The application of cell line microarrays to
      the assessment of biologic marker evaluation was validated by studying the
      immunohistochemical expression of PTEN and phosphorylated AKT, two mediators of
      the phosphatidylinositol (PI)-3-kinase pathway. In addition to the high
      throughout analysis of protein expression in lymphoma/leukemia cells, this
      methodology also enables the evaluation of subcellular localization of protein
      expression. Cytoplasmic PTEN expression was observed in the majority of cell
      lines (87%), whereas a minor subset demonstrated nuclear expression.
      Phosphorylated AKT was also expressed predominantly within the cytoplasm in 65%
      of cell lines, whereas nuclear expression was seen in a minority. An inverse
      relationship between PTEN and phosphorylated AKT was observed in 63% of cell
      lines. No cell lines showed absence of PTEN expression, whereas 50% of cell lines
      showed low PTEN expression. Our data support the integrity of the PI-3-kinase
      PTEN-AKT pathway in a majority of cell lines derived from hematologic
      malignancies and clearly demonstrates the utility of microarray technology in the
      in situ assessment of expression of molecular markers in tumor-derived cell
      lines.

PMID- 12808068
TI  - Adenomatoid tumor of the pancreas: a case report with comparison of histology and
      aspiration cytology.
AB  - We present a 58-year-old woman who presented with a 1.5-cm, hypodense lesion in
      the head of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration
      yielded bland, monotonous cells with wispy cytoplasm, slightly granular
      chromatin, and small nucleoli. A presumptive diagnosis of a neuroendocrine lesion
      was rendered. Whipple procedure yielded a well-circumscribed, encapsulated lesion
      with dense, hyalinized stroma and a peripheral rim of lymphocytes. Spindled and
      epithelioid cells formed short tubules, cords, and nests. The neoplasm stained
      for CK 5/6, calretinin, vimentin, CD 99, pancytokeratin, and EMA, consistent with
      mesothelial origin. This characteristic histology and immunohistochemistry is
      consistent with an adenomatoid tumor. We believe we are the first to report this
      benign neoplasm in such an unusual location. Herein we address the diagnosis of
      adenomatoid tumor by histology, immunohistochemistry, and aspiration cytology.
      Our case is particularly unique in that the histology and cytology are compared
      and correlated.

PMID- 12808069
TI  - Correspondence re: Mikami Y, Hata S, Kiyokawa T, Manabe T. Expression of CD10 in
      malignant mullerian mixed tumors and adenosarcomas: an immunohistochemical study.
      Mod pathol 2002;15:923-30.

PMID- 12808071
TI  - Overexpression of Bcl-W in the testis disrupts spermatogenesis: revelation of a
      role of BCL-W in male germ cell cycle control.
AB  - To explore physiological roles of BCL-W, a prosurvival member of the BCL-2
      protein family, we generated transgenic (TG) mice overexpressing Bcl-w driven by
      a chicken beta-actin promoter. Male Bcl-w TG mice developed normally but were
      infertile. The adult TG testes displayed disrupted spermatogenesis with various
      severities ranging from thin seminiferous epithelium containing less germ cells
      to Sertoli cell-only appearance. No overpopulation of any type of germ cells was
      observed during testicular development. In contrast, the developing TG testes
      displayed decreased number of spermatogonia, degeneration, and detachment of
      spermatocytes and Sertoli cell vacuolization. The proliferative activity of germ
      cells was significantly reduced during testicular development and
      spermatogenesis, as determined by in vivo and in vitro 5'-bromo-2'deoxyuridine
      incorporation assays. Sertoli cells were structurally and functionally normal.
      The degenerating germ cells were TUNEL-negative and no typical apoptotic DNA
      ladder was detected. Our data suggest that regulated spatial and temporal
      expression of BCL-W is required for normal testicular development and
      spermatogenesis, and overexpression of BCL-W inhibits germ cell cycle entry
      and/or cell cycle progression leading to disrupted spermatogenesis.

PMID- 12808072
TI  - Chlamydial vaccine development.

PMID- 12808073
TI  - Microbial dinner-party conversations: the role of LuxS in interspecies
      communication.
AB  - Bacteria have a tendency to be gregarious by nature. Whether on abiotic surfaces
      in the environment or on the mucosal surfaces of humans, bacteria accumulate in
      complex multi-species communities. In these dynamic accretions, bacteria can be
      densely packed and often depend on each other for the provision of metabolic
      substrates. Under these circumstances, it will be advantageous for bacteria to be
      able to detect the presence of their neighbours, to communicate with them and to
      co-ordinate various physiological activities. Such cell-cell sensing and
      communication systems can be established through the release and detection of
      chemical signalling molecules. While originally considered a feature
      characteristic of eukaryotes, the exchange of chemical signals has now been
      demonstrated in many bacterial species and ecosystems. Indeed, it has even been
      suggested that assemblages of bacterial species can be considered as proto
      multicellular organisms, whereby biological processes are controlled for the
      benefit of the entire community. Regardless of the extent to which bacterial
      communication represents a step on the road to multicellularity, it is becoming
      increasingly apparent that the signalling systems devised by bacteria are
      essential for successful relationships with other bacteria and with eukaryotic
      hosts.

PMID- 12808074
TI  - Correlation between enterococcal biofilm formation in vitro and medical-device
      related infection potential in vivo.
AB  - Hospital-acquired infections caused by enterococci have increased dramatically
      since the 1970s. Many nosocomial enterococcal bloodstream infections are
      associated with medical devices such as central venous catheters. The ability to
      form biofilm on medical devices is a potential virulence trait that may allow
      enterococci to cause infections in the expanding population of patients managed
      with such devices. In this study, the hypothesis that increased ability to form
      biofilm in vitro is associated with medical-device-related infection in vivo was
      tested. A microplate assay was employed to assess biofilm-forming characteristics
      of enterococci in 0.9 % (w/v) sodium chloride, an oligotrophic environment, and
      BHI, a nutrient-rich environment. Results were compared in isolates from
      different sources of infection. One hundred and nine enterococcal bloodstream
      isolates were assayed. Biofilm formation on microplates was demonstrated by all
      Enterococcus faecalis isolates and 16/38 (42 %) Enterococcus faecium isolates. E.
      faecalis isolates produced significantly more biofilm than E. faecium isolates in
      both media (P < 0.0001, Mann-Whitney U test). E. faecalis isolates from
      intravascular-catheter-related bloodstream infections (CRBSIs) produced
      significantly more biofilm than non-CRBSI isolates (P < 0.0001), or isolates of
      uncertain clinical significance (P < 0.0001). Biofilm formed by E. faecium
      isolates was not significantly affected by culture medium and did not differ
      between isolates from the different clinical categories. In conclusion, there was
      significantly more biofilm formed by E. faecalis isolates causing CRBSI compared
      with isolates from other types of infection or from isolates of uncertain
      clinical significance. The ability of E. faecalis isolates to form biofilm in
      vitro appears to be a marker of a virulence trait that enhances the ability of
      isolates to cause CRBSI.

PMID- 12808075
TI  - Inability of outer-surface protein C (OspC)-primed mice to elicit a protective
      anamnestic immune response to a tick-transmitted challenge of Borrelia
      burgdorferi.
AB  - A one-inoculation regimen of recombinant outer-surface protein C (OspC), which
      has been demonstrated to elicit protective immunity against a tick-borne
      challenge of Borrelia burgdorferi, was administered to outbred mice. Following
      seroconversion, the serum antibody titre against OspC was allowed to wane with
      time until there was little or no detection of anti-OspC antibodies by
      immunoblot. The mice were then challenged with an infectious dose of B.
      burgdorferi by tick transmission. Eleven of 12 OspC-primed mice subsequently
      became infected by B. burgdorferi, demonstrating that a protective anamnestic
      response was not generated in these mice following the introduction of infectious
      OspC-expressing spirochaetes.

PMID- 12808076
TI  - Rapid identification and susceptibility testing of Mycobacterium tuberculosis
      from MGIT cultures with luciferase reporter mycobacteriophages.
AB  - In a prospective study conducted in a diagnostic laboratory in Mexico City,
      luciferase reporter mycobacteriophages (LRPs) were evaluated for their utility
      and performance in identification and antibiotic-susceptibility testing of
      Mycobacterium tuberculosis complex (MTC) isolates from MGIT-960 cultures. Eighty
      four consecutive MGIT cultures recovered from 54 patients were included in this
      study. The LRPs confirmed mycobacterial growth in 79 (94 %) of 84 MGIT cultures.
      Failure to confirm growth was due to low inoculum (n = 1) or growth with non
      tuberculous mycobacteria (n = 4). The median time to confirmation of MGIT
      cultures was 1 day (range 1-55). Confirmed cultures were identified with p-nitro
      alpha-acetylamino-beta-hydroxypropiophenone (NAP), a selective inhibitor of MTC
      species, and results obtained with LRPs were compared with those obtained by
      BACTEC-460. The sensitivity and specificity of the LRP NAP test were respectively
      97 and 100 %, and the median turnaround time for identification was 3 days with
      both methods. The accuracy and speed of the LRPs for susceptibility testing with
      rifampicin, streptomycin, isoniazid and ethambutol were compared with BACTEC-460
      and discrepant results were tested by the conventional agar proportion method. In
      total, 72 MTC cultures were tested. The overall agreement between the LRPs and
      BACTEC-460 was 98.6 %. Four isolates (5.6 %) were falsely identified as
      ethambutol-resistant. The median turnaround time for susceptibility testing was 3
      days (range 3-57) with the LRPs and 9 days (range 7-29) with BACTEC-460. LRPs
      offer an accurate and rapid approach for identification and susceptibility
      testing of M. tuberculosis from MGIT-960 cultures.

PMID- 12808077
TI  - Improved serodiagnosis of erythema migrans using novel recombinant borrelial
      BBK32 antigens.
AB  - The performances of recombinant borrelial BBK32 proteins as antigens in the
      serology of erythema migrans (EM) were evaluated in an ELISA. Serum samples were
      obtained from 75 patients from different geographic areas where three borrelial
      species, Borrelia burgdorferi sensu stricto, Borrelia afzelii or Borrelia
      garinii, cause Lyme borreliosis. Antibodies to variant BBK32 proteins were
      compared with anti-flagella or with anti-IR(6) peptide antibodies. In IgG ELISA
      at presentation of EM, 65/75 (87 %) patients had antibodies to one or more
      variants of BBK32, 29/75 (39 %) had antibodies to flagella and 29/75 (39 %) had
      antibodies to the VlsE IR(6) peptide antigen. The immunoreactivity against
      variant BBK32 proteins differed in patients from different geographic regions.
      The present results suggest that the BBK32 proteins used in combination or in
      parallel may improve the laboratory diagnosis of EM.

PMID- 12808078
TI  - Analysis of saliva for antibodies to the LPS of Escherichia coli O157 in patients
      with serum antibodies to E. coli O157 LPS.
AB  - The salivary antibody response to the Escherichia coli O157 LPS antigen was
      assessed in 44 patients with serum antibodies binding to the LPS of E. coli O157.
      Saliva from 477 controls was also examined to assess the specificity of the
      immunoassay used. Twenty of the 44 patients had salivary antibodies to E. coli
      O157 LPS, giving the salivary antibody test a sensitivity of 0.45 and a
      predictive positive value for seropositivity of 1.00. The presence of these
      antibodies appeared not to relate to the time interval between serum sampling and
      saliva sampling. None of the 477 volunteers had salivary antibodies binding to
      the LPS of E. coli O157 alone; however, 15 had antibodies which bound non
      specifically to both O157 LPS and BSA.

PMID- 12808079
TI  - Clostridium difficile in a geriatric unit: a prospective epidemiological study
      employing a novel S-layer typing method.
AB  - Clostridium difficile is the major identifiable cause of antibiotic-associated
      diarrhoea in the UK. The aim of this study was to employ traditional culture,
      toxin detection and a novel typing method to determine the level of C. difficile
      colonization and disease in a population of elderly patients and to investigate
      the association between strains in the patients and their environment. Three
      hundred and ninety patients between 62 and 101 years of age admitted to a
      geriatric unit in the Royal Victoria Hospital (RVH), Edinburgh, were investigated
      for the presence of C. difficile. C. difficile was cultured from 100 (26 %)
      patients using pre-reduced cycloserine-cefoxitin egg yolk agar, and toxin(s) was
      detected in the faeces of 34 of these patients using the Techlab ELISA test kit
      for the detection of C. difficile toxins A and/or B. Toxin(s) was detected in a
      further 18 patients from whom no C. difficile was detected in culture. Of the
      patients in whom C. difficile was detected, 49 % had diarrhoea, with the highest
      proportion of patients with diarrhoea being both culture- and toxin-positive for
      C. difficile. Environmental sampling of the patient environment yielded C.
      difficile from 14 % of samples. The organism was most frequently isolated from
      floors, sluice-rooms and toilet areas. The variation in the molecular mass of the
      C. difficile S-layer proteins was exploited as the basis of a novel typing method
      for C. difficile. Isolates from patients in the RVH were given a four-digit 'S
      type' number based on their S-layer protein profile. A total of seven S-types
      were identified, with one type, toxigenic S-type 5236, accounting for 73 % of all
      clinical isolates and 91 % of environmental isolates.

PMID- 12808080
TI  - Comparative viral frequency in Mexican children under 5 years of age with and
      without upper respiratory symptoms.
AB  - In Mexico, there is a lack of up-to-date published data that show viruses to be
      the main cause of acute respiratory infection (ARI). The objective of this study
      was to estimate the comparative viral frequency between children under the age of
      5 years with and without ARI (n = 179 in each group) in a suburban community
      (Nezahualcoyotl City). A nasopharyngeal sample was collected for viral culture
      and identification was carried out by indirect immunofluorescence (IIF) using
      mAbs. There were no sex differences between the two groups. Children under 1 year
      of age with ARI showed a higher frequency (56 %) of viral infections; this was
      statistically significant (P < 0.05) when compared with the same age group in ARI
      free children (17 %). Respiratory syncytial virus (RSV) was the most prevalent
      type of virus isolated from both groups (38 vs 18 %). A statistically
      significantly higher number of subjects with ARI (33/179) than without (12/179)
      were infected with RSV (P < 0.003). Prevalences of four other viruses studied
      were similar in the two groups. The highest viral incidence of ARI in children
      was detected in the winter-spring seasonal period.

PMID- 12808081
TI  - Identification of a novel antigen of pathogenic Leptospira spp. that reacted with
      convalescent mice sera.
AB  - The virulence of leptospires isolated from human patients against C3H/HeJ mice
      was investigated. Infection with clinical isolates from patients with severe
      leptospirosis was lethal to C3H/HeJ mice, suggesting that C3H/HeJ mice are
      suitable as an acute lethal model of severe leptospirosis. Using this model, a
      novel antigen of pathogenic Leptospira spp. (named LAg42), which reacted with
      convalescent mice sera, was identified. LAg42 is a 42 kDa inner-membrane protein
      and its immunogenic region is located in the C-terminal region. The gene for
      LAg42 is conserved among pathogenic leptospires but not among non-pathogenic
      leptospires, which suggests its involvement in virulence.

PMID- 12808082
TI  - Molecular analysis of bacterial flora associated with chronically inflamed
      maxillary sinuses.
AB  - Chronic maxillary sinusitis is a chronic inflammatory condition in which the role
      of microbial infection remains undefined. Bacteria have been isolated from
      chronically inflamed sinuses; however, their role in the chronicity of
      inflammation is unknown. The objective of this study was to determine whether
      bacteria are present in clinical samples from chronic maxillary sinusitis and to
      assess the diversity of the flora present. Washes and/or tissue samples from
      endoscopic sinus surgery on 11 patients with chronic maxillary sinusitis were
      subjected to PCR amplification of bacterial 16S rDNA using three universal primer
      pairs, followed by cloning and sequencing. The samples were also assessed for the
      presence of bacteria and fungi by conventional culture methods. Viable bacteria
      and/or bacterial 16S rDNA were detected from maxillary sinus samples of five of
      the 11 patients examined (45 %). Three sinus samples were positive by both PCR
      and culture methods, one was positive only by PCR, and one only by culture.
      Thirteen bacterial species were identified: Abiotrophia defectiva, Enterococcus
      avium, Eubacterium sp., Granulicatella elegans, Neisseria sp., Prevotella sp.,
      Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus,
      Stenotrophomonas maltophilia, Streptococcus gordonii, Streptococcus
      mitis/Streptococcus oralis and Streptococcus sp. Fungi were not detected. In one
      patient Streptococcus mitis/Streptococcus oralis, and in another patient
      Pseudomonas aeruginosa, were detected from both the sinus and the oral cavity
      using species-specific PCR primers. These results suggest that both aerobic and
      anaerobic bacteria can be detected in nearly half of chronic maxillary sinusitis
      cases.

PMID- 12808083
TI  - Septicaemia due to Corynebacterium striatum: molecular confirmation of entry via
      the skin.
AB  - Septicaemia due to Corynebacterium striatum occurs infrequently. A case of C.
      striatum septicaemia with a known skin focus is reported in a 69-year-old male
      with ischaemia, refractory anaemia and treated for thyroid cancer. The
      characterization and typing of blood and cutaneous isolates was carried out using
      biochemical and DNA molecular typing methods to analyse the isolates. This is the
      first reported case with a documented source.

PMID- 12808084
TI  - Genomovar distribution of the Burkholderia cepacia complex differs significantly
      between Czech and Slovak patients with cystic fibrosis.

PMID- 12808085
TI  - Akt regulates basic helix-loop-helix transcription factor-coactivator complex
      formation and activity during neuronal differentiation.
AB  - Neural basic helix-loop-helix (bHLH) transcription factors regulate neurogenesis
      in vertebrates. Signaling by peptide growth factors also plays critical roles in
      regulating neuronal differentiation and survival. Many peptide growth factors
      activate phosphatidylinositol 3-kinase (PI3K) and subsequently the Akt kinases,
      raising the possibility that Akt may impact bHLH protein function during
      neurogenesis. Here we demonstrate that reducing expression of endogenous Akt1 and
      Akt2 by RNA interference (RNAi) reduces neuron generation in P19 cells
      transfected with a neural bHLH expression vector. The reduction in neuron
      generation from decreased Akt expression is not solely due to decreased cell
      survival, since addition of the caspase inhibitor z-VAD-FMK rescues cell death
      associated with loss of Akt function but does not restore neuron formation. This
      result indicates that Akt1 and Akt2 have additional functions during neuronal
      differentiation that are separable from neuronal survival. We show that activated
      Akt1 enhances complex formation between bHLH proteins and the transcriptional
      coactivator p300. Activated Akt1 also significantly augments the transcriptional
      activity of the bHLH protein neurogenin 3 in complex with the coactivators p300
      or CBP. In addition, inhibition of endogenous Akt activity by the PI3K/Akt
      inhibitor LY294002 abolishes transcriptional cooperativity between the bHLH
      proteins and p300. We propose that Akt regulates the assembly and activity of
      bHLH-coactivator complexes to promote neuronal differentiation.

PMID- 12808087
TI  - Enhancer sequences influence the role of the amino-terminal domain of bicoid in
      transcription.
AB  - Bicoid (Bcd) is a Drosophila melanogaster morphogenetic gradient that controls
      embryonic patterning by activating target gene expression in a concentration
      dependent manner. In this study we describe experiments to determine how
      different enhancers respond to Bcd distinctively, focusing on two natural Bcd
      responsive enhancer elements, hunchback (hb) and knirps (kni). Our results show
      that, on the hb enhancer element, the amino-terminal domain of Bcd (residues 1 to
      91) plays primarily an inhibitory role, whereas on the kni enhancer element this
      same Bcd domain plays a positive role at low protein concentrations. We further
      demonstrate that while the amino-terminal domain is largely dispensable for
      cooperative binding to the hb enhancer element, it is preferentially required for
      cooperative binding to the kni enhancer element. Alteration of the arrangement of
      Bcd binding sites in the kni enhancer element reduces the role of the amino
      terminal domain in cooperative DNA binding but increases the effectiveness of the
      self-inhibitory function. In addition, elimination of symmetric pairs of Bcd
      binding sites in the kni enhancer element reduces both DNA binding and activation
      by Bcd. We propose that the amino-terminal domain of Bcd is an enhancer-specific
      switch that contributes to the protein's ability to activate different target
      genes in distinct manners.

PMID- 12808086
TI  - Use of Bmp1/Tll1 doubly homozygous null mice and proteomics to identify and
      validate in vivo substrates of bone morphogenetic protein 1/tolloid-like
      metalloproteinases.
AB  - Bone morphogenetic protein 1 (BMP-1) and mammalian Tolloid (mTLD), two
      proteinases encoded by Bmp1, provide procollagen C-proteinase (pCP) activity that
      converts procollagens I to III into the major fibrous components of mammalian
      extracellular matrix (ECM). Yet, although Bmp1(-/-) mice have aberrant collagen
      fibrils, they have residual pCP activity, indicative of genetic redundancy.
      Mammals possess two additional proteinases structurally similar to BMP-1 and
      mTLD: the genetically distinct mammalian Tolloid-like 1 (mTLL-1) and mTLL-2. Mice
      lacking the mTLL-1 gene Tll1 are embryonic lethal but have pCP activity levels
      similar to those of the wild type, suggesting that mTLL-1 might not be an in vivo
      pCP. In vitro studies have shown BMP-1 and mTLL-1 capable of cleaving Chordin, an
      extracellular antagonist of BMP signaling, suggesting that these proteases might
      also serve to modulate BMP signaling and to coordinate the latter with ECM
      formation. However, in vivo evidence of roles for BMP-1 and mTLL-1 in BMP
      signaling in mammals is lacking. To remove functional redundancy obscuring the in
      vivo functions of BMP-1-related proteases in mammals, we here characterize Bmp1
      Tll1 doubly null mouse embryos. Although these appear morphologically
      indistinguishable from Tll1(-/-) embryos, biochemical analysis of cells derived
      from doubly null embryos shows functional redundancy removed to an extent
      enabling us to demonstrate that (i) products of Bmp1 and Tll1 are responsible for
      in vivo cleavage of Chordin in mammals and (ii) mTLL-1 is an in vivo pCP that
      provides residual activity observed in Bmp1(-/-) embryos. Removal of functional
      redundancy also enabled use of Bmp1(-/-) Tll1(-/-) cells in a proteomics approach
      for identifying novel substrates of Bmp1 and Tll1 products.

PMID- 12808088
TI  - Sequential protein association with nascent 60S ribosomal particles.
AB  - Ribosome biogenesis in eukaryotes depends on the coordinated action of ribosomal
      and nonribosomal proteins that guide the assembly of preribosomal particles.
      These intermediate particles follow a maturation pathway in which important
      changes in their protein composition occur. The mechanisms involved in the
      coordinated assembly of the ribosomal particles are poorly understood. We show
      here that the association of preribosomal factors with pre-60S complexes depends
      on the presence of earlier factors, a phenomenon essential for ribosome
      biogenesis. The analysis of the composition of purified preribosomal complexes
      blocked in maturation at specific steps allowed us to propose a model of
      sequential protein association with, and dissociation from, early pre-60S
      complexes for several preribosomal factors such as Mak11, Ssf1, Rlp24, Nog1, and
      Nog2. The presence of either Ssf1 or Nog2 in complexes that contain the 27SB pre
      rRNA defines novel, distinct pre-60S particles that contain the same pre-rRNA
      intermediates and that differ only by the presence or absence of specific
      proteins. Physical and functional interactions between Rlp24 and Nog1 revealed
      that the assembly steps are, at least in part, mediated by direct protein-protein
      interactions.

PMID- 12808089
TI  - Silencing of mouse Aprt is a gradual process in differentiated cells.
AB  - Mouse Aprt constructs that are highly susceptible to DNA methylation-associated
      inactivation in embryonal carcinoma cells were transfected into differentiated
      cells, where they were expressed. Construct silencing was induced by either whole
      cell fusion of the expressing differentiated cells with embryonal carcinoma cells
      or by treatment of the differentiated cells with the DNA demethylating agent 5
      aza-2'-deoxycytidine. Induction of silencing was enhanced significantly by the
      presence of a methylation center fragment positioned upstream of a truncated
      promoter comprised of two functional Sp1 binding sites. Initial silencing of the
      Aprt constructs was unstable, as evidenced by high spontaneous reversion
      frequencies ( approximately 10(-2)). Stably silenced subclones with spontaneous
      reversion frequencies of <10(-5) were isolated readily from the unstably silenced
      clones. These reversion frequencies were enhanced significantly by treatment of
      the cells with 5-aza-2'-deoxycytidine. A bisulfite sequence analysis demonstrated
      that CpG methylation initiated within the methylation center region on expressing
      alleles and that the induction of silencing allowed methylation to spread towards
      and eventually into the promoter region. Combined with the induction of
      revertants by 5-aza-2'-deoxycytidine, this result suggested that stabilization of
      silencing was due to an increased density of CpG methylation. All allelic
      methylation patterns were variegated, which is consistent with a gradual and
      evolving process. In total, our results demonstrate that silencing of mouse Aprt
      is a gradual process in the differentiated cells.

PMID- 12808090
TI  - Gab1 is an integrator of cell death versus cell survival signals in oxidative
      stress.
AB  - Upon the addition of different growth factors and cytokines, the Gab1 docking
      protein is tyrosine phosphorylated and in turn activates different signaling
      pathways. On the basis of the large body of evidence concerning cross talk
      between the signaling pathways activated by growth factors and oxidative stress,
      we decided to investigate the role of Gab1 in oxidative injury. We stimulated
      wild-type mouse embryo fibroblasts (MEF) or MEF with a homozygous deletion of the
      Gab1 gene (-/- MEF) with H(2)O(2). Our results show that Gab1 is phosphorylated
      in a dose- and time-dependent manner after H(2)O(2) triggering. Gab1 then
      recruits molecules such as SHP2, phosphatidylinositol 3-kinase (PI3K), and Shc.
      Gab1 phosphorylation is sensitive to the Src family kinase inhibitor PP2.
      Furthermore, we demonstrate that Gab1 is required for H(2)O(2)-induced c-Jun N
      terminal kinase (JNK) activation but not for ERK2 or p38 activation.
      Reconstitution of Gab1 in -/- MEF rescues JNK activation, and we find that this
      is dependent on the SHP2 binding site in Gab1. Cell viability assays reveal that
      Gab1 has a dual role in cell survival: a positive one through its interaction
      with PI3K and a negative one through its interaction with SHP2. This is the first
      report identifying Gab1 as a component in oxidative stress signaling and one that
      is required for JNK activation.

PMID- 12808091
TI  - Selectable system for monitoring the instability of CTG/CAG triplet repeats in
      mammalian cells.
AB  - Despite substantial progress in understanding the mechanism by which expanded
      CTG/CAG trinucleotide repeats cause neurodegenerative diseases, little is known
      about the basis for repeat instability itself. By taking advantage of a novel
      phenomenon, we have developed a selectable assay to detect contractions of
      CTG/CAG triplets. When inserted into an intron in the APRT gene or the HPRT
      minigene, long tracts of CTG/CAG repeats (more than about 33 repeat units) are
      efficiently incorporated into mRNA as a new exon, thereby rendering the encoded
      protein nonfunctional, whereas short repeat tracts do not affect the phenotype.
      Therefore, contractions of long repeats can be monitored in large cell
      populations, by selecting for HPRT(+) or APRT(+) clones. Using this selectable
      system, we determined the frequency of spontaneous contractions and showed that
      treatments with DNA-damaging agents stimulate repeat contractions. The selectable
      system that we have developed provides a versatile tool for the analysis of
      CTG/CAG repeat instability in mammalian cells. We also discuss how the effect of
      long CTG/CAG repeat tracts on splicing may contribute to the progression of
      polyglutamine diseases.

PMID- 12808092
TI  - Nuclear factor YY1 inhibits transforming growth factor beta- and bone
      morphogenetic protein-induced cell differentiation.
AB  - Smad proteins transduce transforming growth factor beta (TGF-beta) and bone
      morphogenetic protein (BMP) signals that regulate cell growth and
      differentiation. We have identified YY1, a transcription factor that positively
      or negatively regulates transcription of many genes, as a novel Smad-interacting
      protein. YY1 represses the induction of immediate-early genes to TGF-beta and
      BMP, such as the plasminogen activator inhibitor 1 gene (PAI-1) and the inhibitor
      of differentiation/inhibitor of DNA binding 1 gene (Id-1). YY1 inhibits binding
      of Smads to their cognate DNA elements in vitro and blocks Smad recruitment to
      the Smad-binding element-rich region of the PAI-1 promoter in vivo. YY1 interacts
      with the conserved N-terminal Mad homology 1 domain of Smad4 and to a lesser
      extent with Smad1, Smad2, and Smad3. The YY1 zinc finger domain mediates the
      association with Smads and is necessary for the repressive effect of YY1 on Smad
      transcriptional activity. Moreover, downregulation of endogenous YY1 by antisense
      and small interfering RNA strategies results in enhanced transcriptional
      responses to TGF-beta or BMP. Ectopic expression of YY1 inhibits, while knockdown
      of endogenous YY1 enhances, TGF-beta- and BMP-induced cell differentiation. In
      contrast, overexpression or knockdown of YY1 does not affect growth inhibition
      induced by TGF-beta or BMP. Accordingly, YY1 does not interfere with the
      regulation of immediate-early genes involved in the TGF-beta growth-inhibitory
      response, the cell cycle inhibitors p15 and p21, and the proto-oncogene c-myc. In
      conclusion, YY1 represses Smad transcriptional activities in a gene-specific
      manner and thus regulates cell differentiation induced by TGF-beta superfamily
      pathways.

PMID- 12808093
TI  - Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its
      antiapoptotic action.
AB  - The antiapoptotic protein PED/PEA-15 features an Akt phosphorylation motif
      upstream from Ser(116). In vitro, recombinant PED/PEA-15 was phosphorylated by
      Akt with a stoichiometry close to 1. Based on Western blotting with specific
      phospho-Ser(116) PED/PEA-15 antibodies, Akt phosphorylation of PED/PEA-15
      occurred mainly at Ser(116). In addition, a mutant of PED/PEA-15 featuring the
      substitution of Ser(116)-->Gly (PED(S116-->G)) showed 10-fold-decreased
      phosphorylation by Akt. In intact 293 cells, Akt also induced phosphorylation of
      PED/PEA-15 at Ser(116). Based on pull-down and coprecipitation assays, PED/PEA-15
      specifically bound Akt, independently of Akt activity. Serum activation of Akt as
      well as BAD phosphorylation by Akt showed no difference in 293 cells transfected
      with PED/PEA-15 and in untransfected cells (which express no endogenous PED/PEA
      15). However, the antiapoptotic action of PED/PEA-15 was almost twofold reduced
      in PED(S116-->G) compared to that in PED/PEA-15(WT) cells. PED/PEA-15 stability
      closely paralleled Akt activation by serum in 293 cells. In these cells, the
      nonphosphorylatable PED(S116-->G) mutant exhibited a degradation rate threefold
      greater than that observed with wild-type PED/PEA-15. In the U373MG glioma cells,
      blocking Akt also reduced PED/PEA-15 levels and induced sensitivity to tumor
      necrosis factor-related apoptosis-inducing ligand apoptosis. Thus,
      phosphorylation by Akt regulates the antiapoptotic function of PED/PEA-15 at
      least in part by controlling the stability of PED/PEA-15. In part, Akt survival
      signaling may be mediated by PED/PEA-15.

PMID- 12808094
TI  - Loss of Sin3/Rpd3 histone deacetylase restores the DNA damage response in
      checkpoint-deficient strains of Saccharomyces cerevisiae.
AB  - We previously reported that expression of the human forkhead/winged helix
      transcription factor, CHES1 (checkpoint suppressor 1; FOXN3), suppresses
      sensitivity to DNA damage and restores damage-induced G(2)/M arrest in checkpoint
      deficient strains of Saccharomyces cerevisiae. We find that a functional
      glutathione S-transferase-Ches1 fusion protein binds in vivo to Sin3, a component
      of the S. cerevisiae Sin3/Rpd3 histone deacetylase complex. Checkpoint mutant
      strains with SIN3 deleted show increased resistance to UV irradiation, which is
      not further enhanced by CHES1 expression. Conversely, overexpression of SIN3
      blocks the Ches1-mediated G(2)/M delay in response to DNA damage, which is
      consistent with Ches1 acting by inhibiting the Sin3/Rpd3 complex. Deletion of
      either SIN3 or RPD3 in rad9 or mec1 checkpoint mutant strains suppresses
      sensitivity to replication blocks and DNA damage resulting from Cdc9 ligase
      deficiency and UV irradiation. SIN3 or RPD3 deletions also restored G(2)/M arrest
      after DNA damage without concomitant Rad53 phosphorylation in mec1 mutant
      strains. This DNA damage response is absent in mad1 spindle checkpoint mutants.
      These data suggest that modulation of chromatin structure may regulate checkpoint
      responses in S. cerevisiae. Inhibition of histone deacetylation results in a DNA
      damage checkpoint response mediated by the spindle checkpoint pathway that
      compensates for loss of the primary DNA damage checkpoint pathway.

PMID- 12808095
TI  - Transcriptional program of apoptosis induction following interleukin 2
      deprivation: identification of RC3, a calcium/calmodulin binding protein, as a
      novel proapoptotic factor.
AB  - Apoptosis of mature T lymphocytes preserves immune system homeostasis by
      counteracting transient increases in T-cell number. This process is regulated, at
      least in part, by the cytokine interleukin 2 (IL-2): T cells deprived of IL-2
      undergo apoptosis. The mechanism of apoptosis induction by IL-2 deprivation
      remains to be determined but is known to require RNA synthesis, implying the
      existence of transcriptionally activated genes whose products induce cell death.
      To identify such genes, we have performed expression profiling in IL-2-dependent
      T cells following cytokine deprivation. Our results reveal an intricate
      transcriptional program entailing the induction of known proapoptotic factors and
      the simultaneous repression of known antiapoptotic factors. Surprisingly, one
      gene whose transcription substantially increased was RC3 (also called
      neurogranin), which encodes a calmodulin binding protein thought to be a neural
      specific factor involved in learning and memory. We show that ectopic expression
      of RC3 in IL-2-dependent T cells increases the intracellular Ca(2+) concentration
      and induces apoptosis even in the presence of cytokine. Buffering the Ca(2+)
      increase with the cytoplasmic Ca(2+) chelator BAPTA-AM [1,2-bis(2
      aminophenoxy)ethane-N,N,N1,N-tetraacetic acid] blocks RC3-induced apoptosis,
      indicating that the rise in intracellular Ca(2+) is required for apoptotic death.
      RC3 mutants unable to bind calmodulin fail to increase intracellular Ca(2+)
      levels and to induce apoptosis. Based upon these results, we propose that IL-2
      deprivation raises the level of RC3 and other apoptotic factors, which induce
      apoptosis by increasing the intracellular Ca(2+) concentration.

PMID- 12808096
TI  - Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin
      proteasome pathway defines a novel paradigm of mitogen-activated protein kinase
      regulation during cellular differentiation.
AB  - Mitogen-activated protein (MAP) kinases are stable enzymes that are mainly
      regulated by phosphorylation and subcellular targeting. Here we report that
      extracellular signal-regulated kinase 3 (ERK3), unlike other MAP kinases, is an
      unstable protein that is constitutively degraded in proliferating cells with a
      half-life of 30 min. The proteolysis of ERK3 is executed by the proteasome and
      requires ubiquitination of the protein. Contrary to other protein kinases, the
      catalytic activity of ERK3 is not responsible for its short half-life. Instead,
      analysis of ERK1/ERK3 chimeras revealed the presence of two destabilization
      regions (NDR1 and -2) in the N-terminal lobe of the ERK3 kinase domain that are
      both necessary and sufficient to target ERK3 and heterologous proteins for
      proteasomal degradation. To assess the physiological relevance of the rapid
      turnover of ERK3, we monitored the expression of the kinase in different cellular
      models of differentiation. We observed that ERK3 markedly accumulates during
      differentiation of PC12 and C2C12 cells into the neuronal and muscle lineage,
      respectively. The accumulation of ERK3 during myogenic differentiation is
      associated with the time-dependent stabilization of the protein. Terminal
      skeletal muscle differentiation is accompanied by cell cycle withdrawal.
      Interestingly, we found that expression of stabilized forms of ERK3 causes G(1)
      arrest in NIH 3T3 cells. We propose that ERK3 biological activity is regulated by
      its cellular abundance through the control of protein stability.

PMID- 12808097
TI  - H1 linker histones are essential for mouse development and affect nucleosome
      spacing in vivo.
AB  - Most eukaryotic cells contain nearly equimolar amounts of nucleosomes and H1
      linker histones. Despite their abundance and the potential functional
      specialization of H1 subtypes in multicellular organisms, gene inactivation
      studies have failed to reveal essential functions for linker histones in vivo.
      Moreover, in vitro studies suggest that H1 subtypes may not be absolutely
      required for assembly of chromosomes or nuclei. By sequentially inactivating the
      genes for three mouse H1 subtypes (H1c, H1d, and H1e), we showed that linker
      histones are essential for mammalian development. Embryos lacking the three H1
      subtypes die by mid-gestation with a broad range of defects. Triple-H1-null
      embryos have about 50% of the normal ratio of H1 to nucleosomes. Mice null for
      five of these six H1 alleles are viable but are underrepresented in litters and
      are much smaller than their littermates. Marked reductions in H1 content were
      found in certain tissues of these mice and in another compound H1 mutant. These
      results demonstrate that the total amount of H1 is crucial for proper embryonic
      development. Extensive reduction of H1 in certain tissues did not lead to changes
      in nuclear size, but it did result in global shortening of the spacing between
      nucleosomes.

PMID- 12808098
TI  - Cooperation of cytokine signaling with chimeric transcription factors in
      leukemogenesis: PML-retinoic acid receptor alpha blocks growth factor-mediated
      differentiation.
AB  - We utilized a mouse model of acute promyelocytic leukemia (APL) to investigate
      how aberrant activation of cytokine signaling pathways interacts with chimeric
      transcription factors to generate acute myeloid leukemia. Expression in mice of
      the APL-associated fusion, PML-RARA, initially has only modest effects on
      myelopoiesis. Whereas treatment of control animals with interleukin-3 (IL-3)
      resulted in expanded myelopoiesis without a block in differentiation, PML-RARA
      abrogated differentiation that normally characterizes the response to IL-3.
      Retroviral transduction of bone marrow with an IL-3-expressing retrovirus
      revealed that IL-3 and promyelocytic leukemia-retinoic acid receptor alpha (PML
      RARalpha) combined to generate a lethal leukemia-like syndrome in <21 days. We
      also observed that a constitutively activated mutant IL-3 receptor, beta(c)V449E,
      cooperated with PML-RARalpha in leukemogenesis, whereas a different activated
      mutant, beta(c)I374N, did not. Analysis of additional mutations introduced into
      beta(c)V449E showed that, although tyrosine phosphorylation of beta(c) is
      necessary for cooperation, the Src homology 2 domain-containing transforming
      protein binding site is dispensable. Our results indicate that chimeric
      transcription factors can block the differentiative effects of growth factors.
      This combination can be potently leukemogenic, but the particular manner in which
      these types of mutations interact determines the ability of such combinations to
      generate acute myeloid leukemia.

PMID- 12808099
TI  - The murine Nck SH2/SH3 adaptors are important for the development of mesoderm
      derived embryonic structures and for regulating the cellular actin network.
AB  - Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three
      SH3 domains, followed by an SH2 domain, and are implicated in coupling
      phosphotyrosine signals to polypeptides that regulate the actin cytoskeleton.
      However, the in vivo functions of Nck1 and Nck2 have not been defined. We have
      mutated the murine Nck1 and Nck2 genes and incorporated beta-galactosidase
      reporters into the mutant loci. In mouse embryos, the two Nck genes have broad
      and overlapping expression patterns. They are functionally redundant in the sense
      that mice deficient for either Nck1 or Nck2 are viable, whereas inactivation of
      both Nck1 and Nck2 results in profound defects in mesoderm-derived notochord and
      embryonic lethality at embryonic day 9.5. Fibroblast cell lines derived from
      Nck1(-/-) Nck2(-/-) embryos have defects in cell motility and in the organization
      of the lamellipodial actin network. These data suggest that the Nck SH2/SH3
      adaptors have important functions in the development of mesodermal structures
      during embryogenesis, potentially linked to a role in cell movement and
      cytoskeletal organization.

PMID- 12808100
TI  - Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via
      Src kinase family-dependent phosphorylation of tyrosine 707.
AB  - The regulation of telomerase reverse transcriptase (TERT) plays an important role
      in the proliferative capacity and survival of cells. Here, we report that
      exogenously as well as endogenously induced oxidative stress leads to
      translocation of endogenous as well as overexpressed human TERT from the nucleus
      into the cytosol. TERT is transported through the nuclear pores in a leptomycin
      sensitive and Ran GTPase-dependent process. H(2)O(2)-induced nuclear export of
      TERT is preceded by TERT tyrosine phosphorylation at position 707 and prevented
      by the Src kinase family inhibitor PP1. Oxidative stress-induced nuclear export
      of TERT depends on association with the Ran GTPase. In contrast, mutation of
      tyrosine 707 inhibits phosphorylation induced by oxidative stress and prevents
      association with Ran and nuclear export of TERT. Moreover, inhibition of tyrosine
      phosphorylation at 707 increases the antiapoptotic capacity of TERT. Taken
      together, depletion of nuclear TERT by tyrosine phosphorylation-dependent nuclear
      export of TERT is a novel mechanism for regulation of TERT localization, which
      reduces the antiapoptotic activity of TERT.

PMID- 12808101
TI  - Intracellular segregation of phosphatidylinositol-3,4,5-trisphosphate by insulin
      dependent actin remodeling in L6 skeletal muscle cells.
AB  - Insulin stimulates glucose uptake by recruiting glucose transporter 4 (GLUT4)
      from an intracellular pool to the cell surface through a mechanism that is
      dependent on phosphatidylinositol (PI) 3-kinase (PI3-K) and cortical actin
      remodeling. Here we test the hypothesis that insulin-dependent actin filament
      remodeling determines the location of insulin signaling molecules. It has been
      shown previously that insulin treatment of L6 myotubes leads to a rapid
      rearrangement of actin filaments into submembrane structures where the p85
      regulatory subunit of PI3-K and organelles containing GLUT4, VAMP2, and the
      insulin-regulated aminopeptidase (IRAP) colocalize. We now report that insulin
      receptor substrate-1 and the p110alpha catalytic subunit of PI3-K (but not
      p110beta) also colocalize with the actin structures. Akt-1 was also found in the
      remodeled actin structures, unlike another PI3-K effector, atypical protein
      kinase C lambda. Transiently transfected green fluorescent protein (GFP)-tagged
      pleckstrin homology (PH) domains of general receptor for phosphoinositides-1
      (GRP1) or Akt (ligands of phosphatidylinositol-3,4,5-trisphosphate [PI-3,4,5
      P(3)]) migrated to the periphery of the live cells; in fixed cells, they were
      detected in the insulin-induced actin structures. These results suggest that PI
      3,4,5-P(3) is generated on membranes located within the actin mesh. Actin
      remodeling and GLUT4 externalization were blocked in cells highly expressing GFP
      PH-GRP1, suggesting that PI-3,4,5-P(3) is required for both phenomena. We propose
      that PI-3,4,5-P(3) leads to actin remodeling, which in turn segregates p85alpha
      and p110alpha, thus localizing PI-3,4,5-P(3) production on membranes trapped by
      the actin mesh. Insulin-stimulated actin remodeling may spatially coordinate the
      localized generation of PI-3,4,5-P(3) and recruitment of Akt, ultimately leading
      to GLUT4 insertion at the plasma membrane.

PMID- 12808102
TI  - Bone morphogenetic protein 4 mediates apoptosis of capillary endothelial cells
      during rat pupillary membrane regression.
AB  - Programmed capillary regression is essential for development, but little is known
      about the mechanism behind this phenomenon. In this study, we characterized the
      molecular determinants of capillary regression utilizing the pupillary membrane
      (PM) in the newborn rat's eye. We observed in the 1-day-culture system that
      apoptotic endothelial cells decrease in number with the addition of a natural
      antagonist, Noggin, strongly suggesting the involvement of the bone morphogenetic
      protein (BMP) family in PM regression. In addition, the lens-conditioned medium
      (Lens-CM) induced apoptosis of HUVE cells and inhibited endothelial
      tubulogenesis, which were completely blocked by both Noggin and the BMP4-specific
      neutralizing antibody. Activation of BMP4 pathway in endothelial cells was
      confirmed by both the up-regulation of Msx genes correlated with apoptosis and
      the translocation of Smad1 into the nucleus. We showed a transient expression of
      BMP4 in Lens-CM by immunoprecipitation assay. Furthermore, the transcorneal
      injection of BMP4 in rats enhanced the apoptosis of PMs, while that of Noggin
      attenuated it. These results indicate that BMP4 pathways play pivotal roles in
      capillary regression in a paracrine manner between lens and PMs.

PMID- 12808103
TI  - Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism
      of retinoic acid synthesis in the developing retina.
AB  - Genetic studies have shown that retinoic acid (RA) signaling is required for
      mouse retina development, controlled in part by an RA-generating aldehyde
      dehydrogenase encoded by Aldh1a2 (Raldh2) expressed transiently in the optic
      vesicles. We examined the function of a related gene, Aldh1a1 (Raldh1), expressed
      throughout development in the dorsal retina. Raldh1(-/-) mice are viable and
      exhibit apparently normal retinal morphology despite a complete absence of Raldh1
      protein in the dorsal neural retina. RA signaling in the optic cup, detected by
      using a RARE-lacZ transgene, is not significantly altered in Raldh1(-/-) embryos
      at embryonic day 10.5, possibly due to normal expression of Aldh1a3 (Raldh3) in
      dorsal retinal pigment epithelium and ventral neural retina. However, at E16.5
      when Raldh3 is expressed ventrally but not dorsally, Raldh1(-/-) embryos lack
      RARE-lacZ expression in the dorsal retina and its retinocollicular axonal
      projections, whereas normal RARE-lacZ expression is detected in the ventral
      retina and its axonal projections. Retrograde labeling of adult Raldh1(-/-)
      retinal ganglion cells indicated that dorsal retinal axons project to the
      superior colliculus, and electroretinography revealed no defect of adult visual
      function, suggesting that dorsal RA signaling is unnecessary for retinal ganglion
      cell axonal outgrowth. We observed that RA synthesis in liver of Raldh1(-/-) mice
      was greatly reduced, thus showing that Raldh1 indeed participates in RA synthesis
      in vivo. Our findings suggest that RA signaling may be necessary only during
      early stages of retina development and that if RA synthesis is needed in dorsal
      retina, it is catalyzed by multiple enzymes, including Raldh1.

PMID- 12808104
TI  - Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes
      involves inhibition of nuclear factor kappaB signaling.
AB  - Recent studies have revealed a positive correlation between astrocyte apoptosis
      and rapid disease progression in persons with neurodegenerative diseases.
      Glycogen synthase kinase 3beta (GSK-3beta) is a molecular regulator of cell fate
      in the central nervous system and a target of the phosphatidylinositol 3-kinase
      (PI-3K) pathway. We have therefore examined the role of the PI-3K pathway, and of
      GSK-3beta, in regulating astrocyte survival. Our studies indicate that inhibition
      of PI-3K leads to apoptosis in primary cortical astrocytes. Furthermore,
      overexpression of a constitutively active GSK-3beta mutant (S9A) is sufficient to
      cause astrocyte apoptosis, whereas an enzymatically inactive GSK-3beta mutant
      (K85M) has no effect. In light of reports on the interplay between GSK-3beta and
      nuclear factor kappaB (NF-kappaB), and because of the antiapoptotic activity of
      NF-kappaB, we examined the effect of GSK-3beta overexpression on NF-kappaB
      activation. These experiments revealed strong inhibition of NF-kappaB activation
      in astrocytes upon overexpression of the S9A, but not the K85M, mutant of GSK
      3beta. This was accompanied by stabilization of the NF-kappaB-inhibitory protein,
      IkappaBalpha and down-regulation of IkappaB kinase (IKK) activity. These findings
      therefore implicate GSK-3beta as a regulator of NF-kappaB activation in
      astrocytes and suggest that the pro-apoptotic effects of GSK-3beta may be
      mediated at least in part through the inhibition of NF-kappaB pathway.

PMID- 12808105
TI  - The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to
      its PDZ domain.
AB  - The protein kinase Bcr is a negative regulator of cell proliferation and
      oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the
      cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF
      6, which subsequently allows efficient binding of Bcr to AF-6, showing that the
      Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6
      colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6,
      and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a
      mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced
      binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6,
      interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since
      AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we
      propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to
      cellular junctions. We suggest that this trimeric complex is involved in
      downregulation of Ras-mediated signaling at sites of cell-cell contact to
      maintain cells in a nonproliferating state.

PMID- 12808106
TI  - Nrf1 is critical for redox balance and survival of liver cells during
      development.
AB  - The Nrf1 transcription factor belongs to the CNC subfamily of basic leucine
      zipper proteins. Knockout of Nrf1 is lethal in mouse embryos, but nothing is
      known about the cell types that absolutely require its function during
      development. We show by chimera analysis that Nrf1 is essential for the
      hepatocyte lineage. Mouse embryonic stem cells lacking Nrf1 developed normally
      and contributed to most tissues in adult chimeras where Nrf1 is normally
      expressed. Nrf1-deficient cells contributed to fetal, but not adult, liver cells.
      Loss of Nrf1 function resulted in liver cell apoptosis in late-gestation chimeric
      fetuses. Fetal livers from mutant embryos exhibited increased oxidative stress
      and impaired expression of antioxidant genes, and primary cultures of nrf1(-/-)
      fetal hepatocytes were sensitive to tert-butyl hydroperoxide-induced cell death,
      suggesting that impaired antioxidant defense may be responsible for the apoptosis
      observed in the livers of chimeric mice. In addition, cells deficient in Nrf1
      were sensitized to the cytotoxic effects of tumor necrosis factor (TNF). Our
      results provide in vivo evidence demonstrating an essential role of Nrf1 in the
      survival of hepatocytes during development. Our results also suggest that Nrf1
      may promote cell survival by maintaining redox balance and protecting embryonic
      hepatocytes from TNF-mediated apoptosis during development.

PMID- 12808107
TI  - Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal
      downstream UCAU-rich intronic splicing enhancer.
AB  - Nova is a neuron-specific RNA binding protein targeted in patients with the
      autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia, which is
      characterized by failure of inhibition of brainstem and spinal motor systems.
      Here, we have biochemically confirmed the observation that splicing regulation of
      the inhibitory GABA(A) receptor gamma2 (GABA(A)Rgamma2) subunit pre-mRNA exon E9
      is disrupted in mice lacking Nova-1. To elucidate the mechanism by which Nova-1
      regulates GABA(A)Rgamma2 alternative splicing, we systematically screened
      minigenes derived from the GABA(A)Rgamma2 and human beta-globin genes for their
      ability to support Nova-dependent splicing in transient transfection assays.
      These studies demonstrate that Nova-1 acts directly on GABA(A)Rgamma2 pre-mRNA to
      regulate E9 splicing and identify an intronic region that is necessary and
      sufficient for Nova-dependent enhancement of exon inclusion, which we term the
      NISE (Nova-dependent intronic splicing enhancer) element. The NISE element
      (located 80 nucleotides upstream of the splice acceptor site of the downstream
      exon E10) is composed of repeats of the sequence YCAY, consistent with previous
      studies of the mechanism by which Nova binds RNA. Mutation of these repeats
      abolishes binding of Nova-1 to the RNA in vitro and Nova-dependent splicing
      regulation in vivo. These data provide a molecular basis for understanding Nova
      regulation of GABA(A)Rgamma2 alternative splicing and suggest that general
      dysregulation of Nova's splicing enhancer function may underlie the neurologic
      defects seen in Nova's absence.

PMID- 12808108
TI  - Nonredundant role of Bax and Bak in Bid-mediated apoptosis.
AB  - Animal models suggest that Bax and Bak play an essential role in the
      implementation of apoptosis and as a result can hinder tumorigenesis. We analyzed
      the expression of these proteins in 50 human glioblastoma multiforme (GBM)
      tumors. We found that all the tumors expressed Bak, while three did not express
      Bax. In vitro, Bax-deficient GBM (BdGBM) exhibited an important resistance to
      various apoptogenic stimuli (e.g., UV, staurosporine, and doxorubicin) compared
      to the Bax-expressing GBM (BeGBM). Using an antisense strategy, we generated Bak(
      ) BeGBM and Bak(-) BdGBM, which enabled us to show that the remaining sensitivity
      of the BdGBM to apoptosis was due to the overexpression of Bak. Bax/Bak single or
      double deficiency had no influence on either the clonogenicity or the growth of
      tumors in Swiss nude mice. Of note, Bak(-) BeGBM cells were resistant to
      apoptosis induced by caspase 8 (C8) but not to that induced by granzyme B (GrB).
      Cells lacking both Bax and Bak (i.e., Bak(-) BdGBM) were completely resistant to
      all stimuli including the microinjection of C8 and GrB. We show that GrB-cleaved
      Bid and C8-cleaved Bid differ in size and utilize preferentially Bax and Bak,
      respectively, to promote cytochrome c release from mitochondria. Our results
      suggest that Bax deficiency is compensated by an increase of the expression of
      Bak in GBM and show, for the first time in human cancer, that the double Bax and
      Bak deficiency severely impairs the apoptotic program.

PMID- 12808109
TI  - p53 represses cyclin D1 transcription through down regulation of Bcl-3 and
      inducing increased association of the p52 NF-kappaB subunit with histone
      deacetylase 1.
AB  - The p53 and NF-kappaB transcription factor families are important,
      multifunctional regulators of the cellular response to stress. Here we have
      investigated the regulatory mechanisms controlling p53-dependent cell cycle
      arrest and cross talk with NF-kappaB. Upon induction of p53 in H1299 or U-2 OS
      cells, we observed specific repression of cyclin D1 promoter activity,
      correlating with a decrease in cyclin D1 protein and mRNA levels. This repression
      was dependent on the proximal NF-kappaB binding site of the cyclin D1 promoter,
      which has been shown to bind the p52 NF-kappaB subunit. p53 inhibited the
      expression of Bcl-3 protein, a member of the IkappaB family that functions as a
      transcriptional coactivator for p52 NF-kappaB and also reduced p52/Bcl-3 complex
      levels. Concomitant with this, p53 induced a significant increase in the
      association of p52 and histone deacetylase 1 (HDAC1). Importantly, p53-mediated
      suppression of the cyclin D1 promoter was reversed by coexpression of Bcl-3 and
      inhibition of p52 or deacetylase activity. p53 therefore induces a
      transcriptional switch in which p52/Bcl-3 activator complexes are replaced by
      p52/HDAC1 repressor complexes, resulting in active repression of cyclin D1
      transcription. These results reveal a unique mechanism by which p53 regulates NF
      kappaB function and cell cycle progression.

PMID- 12808112
TI  - Comparative microarray analysis of gene expression during activation of human
      peripheral blood T cells and leukemic Jurkat T cells.
AB  - Activation of T cells involves a complex cascade of signal transduction pathways
      linking T-cell receptor engagement at the cell membrane to the transcription of
      multiple genes within the nucleus. The T-cell leukemia-derived cell line Jurkat
      has generally been used as a model system for the activation of T cells. However,
      genome-wide comprehensive studies investigating the activation status, and thus
      the appropriateness, of this cell line for this purpose have not been performed.
      We sought to compare the transcriptional profiles of phenotypically purified
      human CD2(+) T cells with those of Jurkat T cells during T-cell activation, using
      cDNA microarrays containing 6912 genes. About 300 genes were up-regulated by more
      than 2-fold during activation of both peripheral blood (PB) T cells and Jurkat T
      cells. The number of down-regulated genes was significantly lower than that of up
      regulated genes. Only 79 genes in PB T cells and 37 genes in Jurkat T cells were
      down-regulated by more than 2-fold during activation. Comparison of gene
      expression during activation of Jurkat and PB T cells revealed a common set of
      genes that were up-regulated, such as Rho GTPase-activating protein 1, SKP2,
      CDC25A, T-cell specific transcription factor 7, cytoskeletal proteins, and
      signaling molecules. Genes that were commonly down-regulated in both PB T cells
      and Jurkat T cells included CDK inhibitors (p16, p19, p27), proapoptotic
      caspases, and the transcription factors c-fos and jun-B. After activation, 71
      genes in PB T cells and only 3 genes in Jurkat T cells were up-regulated 4-fold
      or more. Of these up-regulated genes and expressed sequence tags, 44 were
      constitutively expressed at high levels in nonactivated Jurkat cells.
      Quantitative real-time RT-PCR analysis confirmed our microarray data. Our
      findings indicate that although there is significant overlap in the activation
      associated transcriptional profiles in PB T cells compared with Jurkat T cells,
      there is a subset of genes showing differential expression patterns during the
      activation of the two cell types.

PMID- 12808110
TI  - Schizosaccharomyces pombe checkpoint response to DNA interstrand cross-links.
AB  - Drugs that produce covalent interstrand cross-links (ICLs) in DNA remain central
      to the treatment of cancer, but the cell cycle checkpoints activated by ICLs have
      received little attention. We have used the fission yeast, Schizosaccharomyces
      pombe, to elucidate the checkpoint responses to the ICL-inducing anticancer drugs
      nitrogen mustard and mitomycin C. First we confirmed that the repair pathways
      acting on ICLs in this yeast are similar to those in the main organisms studied
      to date (Escherichia coli, budding yeast, and mammalian cells), principally
      nucleotide excision repair and homologous recombination. We also identified and
      disrupted the S. pombe homologue of the Saccharomyces cerevisiae SNM1/PSO2 ICL
      repair gene and found that this activity is required for normal resistance to
      cross-linking agents, but not other forms of DNA damage. Survival and biochemical
      analysis indicated a key role for the "checkpoint Rad" family acting through the
      chk1-dependent DNA damage checkpoint in the ICL response. Rhp9-dependent
      phosphorylation of Chk1 correlates with G(2) arrest following ICL induction. In
      cells able to bypass the G(2) block, a second-cycle (S-phase) arrest was
      observed. Only a transient activation of the Cds1 DNA replication checkpoint
      factor occurs following ICL formation in wild-type cells, but this is increased
      and persists in G(2) arrest-deficient mutants. This likely reflects the fraction
      of cells escaping the G(2) damage checkpoint and arresting in the subsequent S
      phase due to ICL replication blocks. Disruption of cds1 confers increased
      resistance to ICLs, suggesting that this second-cycle S-phase arrest might be a
      lethal event.

PMID- 12808113
TI  - Binding sites for Lewis antigens are expressed by human colon cancer cells and
      negatively affect their migration.
AB  - In colon cancer, endothelial cell selectins can promote tumor cell attachment via
      interactions with sialylated Lewis antigens present at the surface of tumor
      cells, thereby facilitating tumor cell arrest and transmigration into the
      extravascular space. However, it is not known whether Lewis antigens interact
      with colon tumor cells and modify their migration. Our aim was to detect the
      presence of binding sites on human tumor cells for Lewis(a/x) antigens and their
      sialylated derivatives in vitro and in vivo and to analyze their influence on
      migration of colon cancer cells. The immunocytochemical and histochemical levels
      of expression of the four Lewis antigens were quantitatively determined in four
      human colon cancer cell lines and in in vivo nude mice xenografts. The levels of
      expression of specific binding sites for these sugar epitopes were determined by
      synthetic neoglycoconjugates. The influence of binding of these carbohydrate
      ligands on cancer cell migration was quantitatively evaluated by computer
      assisted phase-contrast videomicroscopy performed on Matrigel culture supports
      either left uncoated or coated with neoglycoconjugate presenting synthetic
      Lewis(a), sialyl Lewis(a), Lewis(x), or sialyl Lewis(x) antigens. The influence
      of the calcium concentration in the culture medium on the Lewis antigen-mediated
      effects was checked. Human colon cancer cells expressed significant amounts of
      specific binding sites detected by the synthetic probes in addition to the
      oligosaccharide epitopes. The expression levels differed considerably between the
      four cell lines and between in vitro and in vivo specimens. Cell migration
      analysis revealed that the four Lewis antigens markedly decreased the levels of
      migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium
      concentration in the culture medium. Binding sites for Lewis epitopes are present
      on colon cancer cells. The functional relevance of these sites is indicated by
      the negative influence on cell migration of a matrix containing the
      oligosaccharides as ligand parts.

PMID- 12808114
TI  - Genetic evaluation of localized prostate cancer in a cohort of forty patients:
      gain of distal 8q discriminates between progressors and nonprogressors.
AB  - Over-representation of sequences on chromosome 7 and 8 have been reported to be
      associated with aggressive behavior of prostate cancer. In this study we have
      performed a molecular cytogenetic survey by comparative genomic hybridization of
      a cohort of 40 prostate cancer patients, consisting of 20 progressors and 20
      nonprogressors, after radical surgery for localized adenocarcinoma. Progression
      was defined as a biochemical relapse, ie, an elevation in prostate-specific
      antigen level in the serum. The mean follow-up after prostatectomy for the
      progressor group was 10.6 years, for the nonprogressor group, 9.1 years. Using
      comparative genomic hybridization, we found that progressors harbored on average
      more aberrations than nonprogressors. Gains were especially more prominent among
      progressors (p < 0.05), whereas a statistical trend was detected for losses (p =
      0.10). As a consequence we examined all chromosome arms separately. The
      frequencies of loss for areas known to be frequently deleted in prostate cancer,
      such as 6q, 8p, or 13q, were not different between the two groups. A tendency was
      observed for more frequent gain on 3q in the progressor group (p = 0.09).
      However, gain of 8q (minimal overlapping region at 8q24-qter) was significantly
      more frequent in the progressor group (p = 0.04). This biomarker retained its
      significance when adjusted for the factors age, tumor grade, tumor stage,
      resection margin status, and preoperative prostate-specific antigen level. In
      conclusion we have created a map of genetic changes in progressive and
      nonprogressive prostatic carcinomas. Importantly, the presence of gain of distal
      8q markedly reduced the progression-free survival, suggesting a clinical role for
      8q gain in assessing the malignant potential of localized prostatic
      adenocarcinoma.

PMID- 12808115
TI  - Functional analysis of EBV in nasopharyngeal carcinoma cells.
AB  - A membrane invasion culture system was used to study the ability of EBV to
      enhance invasion and migration of nasopharyngeal carcinoma (NPC) cells. Semi
      reverse transcriptase-PCR analysis of matrix proteinases and angiogenic factors
      from EBV-infected, or EBV-positive (EBV+), cells demonstrated different degrees
      of elevated gene expression. In our animal model, EBV+ tumors grew faster and
      larger than EBV-free, or EBV-negative (EBV-), tumors and also had clonal EBV
      terminal repeat sequences. Double-localization of EBV and certain host proteins
      in EBV+ tumors and biopsy specimens demonstrated that EBV up-regulates host genes
      only in cells that express those genes but not in cells that do not express them.
      Double-localization of EBV and host genes in NPC biopsy specimens all showed EBV-
      tumor cells expressing those host genes. Our data strongly suggest that EBV
      infection enhances progression of NPC tumor growth. They do not rule out a role
      for EBV infection in the induction and early promotion of NPC development.
      Unidentified factors may also enhance NPC tumor growth independent of the effects
      of EBV.

PMID- 12808116
TI  - Expression of trkB in human neuroblastoma in relation to MYCN expression and
      retinoic acid treatment.
AB  - Expression of full-length trkB can be found in some highly malignant
      neuroblastoma tumors with an amplified MYCN gene. This contrasts sympathetic
      neuroblasts, from which neuroblastomas are thought to arise, which neither
      express trkB nor are dependent on the p145(trkB) ligands, brain-derived
      neurotrophic factor (BDNF) or neurotrophin-4/5, for their normal development. In
      this study we show that trkB was expressed in two out of five neuroblastoma
      tumors with amplified MYCN, while no trkB expression was observed when the MYCN
      gene was overexpressed in a non-MYCN-amplified neuroblastoma cell line. This
      shows that MYCN overexpression per se is not sufficient to induce trkB
      expression. trkB expression and BDNF responsiveness in neuroblastoma cells can be
      induced by all-trans-retinoic acid (RA). When SH-SY5Y cells were stimulated with
      a combination of RA and BDNF, norepinephrine and tyrosine hydroxylase levels were
      unaltered, showing that the cells did not change toward a more catecholaminergic
      sympathetic phenotype. However, expression of growth-associated protein 43,
      indicative of a neuronal phenotype, was elevated. Vesicular acetylcholine
      transporter, choline acetyl transferase, and neuropeptide tyrosine mRNA levels
      also increased in RA-BDNF-treated cells, which could suggest that these cells
      develop into a sympathetic cholinergic phenotype. In addition, treatment with RA
      induced expression of the platelet-derived growth factor receptor-alpha. As
      previously shown for BDNF, platelet-derived growth factor stimulated growth of
      the RA-treated cells, findings that could have clinical relevance. If these
      receptors mediate a mitogenic signal in vivo also, this might limit the effect of
      RA treatment on neuroblastoma patients.

PMID- 12808117
TI  - In chronic pancreatitis, widespread emergence of TRAIL receptors in epithelia
      coincides with neoexpression of TRAIL by pancreatic stellate cells of early
      fibrotic areas.
AB  - TRAIL (TNF-related apoptosis-inducing ligand) induces apoptosis by cross-linking
      of the two TRAIL receptors that contain a death domain, TRAIL-R1 and TRAIL-R2.
      TRAIL-R3 and TRAIL-R4 are receptors that do not transmit an apoptotic signal. Our
      aim was to determine the expression of TRAIL and its receptors in normal pancreas
      and chronic pancreatitis. We applied real-time PCR, immunohisto(cyto)chemistry,
      and nick-end labeling of apoptosis. In normal pancreas, a minor subset of acinar
      cells coexpressed TRAIL-R2 and TRAIL-R4, whereas ductular epithelium and
      interstitial fibroblast-like cells (FLC) expressed TRAIL-R4. TRAIL-R1 and TRAIL
      R3 were not detected in normal pancreas. In chronic pancreatitis, the exocrine
      epithelium strongly expressed TRAIL-R1, -R2, -R4, and, to a lesser extent, TRAIL
      R3. Islets focally neoexpressed TRAIL-R1 and -R2 and intensely expressed TRAIL
      R4. Changes in TRAIL receptor expression were most pronounced in areas of
      inflammatory infiltration and active fibrosis. In normal pancreas, expression of
      TRAIL was low on the mRNA level and undetectable on the protein level. In chronic
      pancreatitis, FLC in areas of active fibrosis expressed TRAIL. In addition,
      apoptosis were most numerous in these areas. We show that these FLC are
      pancreatic stellate cells. Pancreatic stellate cells express TRAIL in vivo and in
      vitro, and TRAIL expression is enhanced by IFN-gamma. Our findings indicate that
      the TRAIL/TRAIL receptor system is likely to be involved in chronic pancreatitis
      and suggest that pancreatic stellate cells may directly contribute to acinar
      regression by inducing apoptosis of parenchymal cells in a TRAIL-dependent
      manner.

PMID- 12808118
TI  - Differential inhibition of prion propagation by enantiomers of quinacrine.
AB  - Prion diseases are fatal neurologic disorders caused by accumulation of a
      pathogenic isoform (PrP(Sc)) of the prion protein (PrP). The recent discovery of
      the inhibitory action of quinacrine on PrP(Sc) formation in scrapie-infected
      neuroblastoma (ScN2a) cells raised the possibility of a treatment for patients
      with prion disease. To investigate the efficacy of quinacrine enantiomers, we
      measured the inhibitory effect of these isomers on PrP(Sc) formation in ScN2a
      cells. (S)-quinacrine exhibited superior antiprion activity compared with (R)
      quinacrine and two generic quinacrines that appear to be racemates. Treatment
      with these various forms of quinacrine did not induce adverse changes affecting
      cell survival and the expression of marker proteins over a range of potentially
      therapeutic concentrations. Thus, quinacrine enantiomers demonstrated
      stereoselectivity on prion elimination but not cytotoxicity in ScN2a cells. Our
      results raise the possibility that in vivo treatment using one enantiomer of
      quinacrine may be superior to a racemic mixture, which is the form that is
      generally used when quinacrine is employed to treat parasitic diseases.

PMID- 12808119
TI  - Improved detection of urothelial carcinomas with fluorescence immunocytochemistry
      (uCyt+ assay) and urinary cytology: results of a French Prospective Multicenter
      Study.
AB  - The aim of the study was to assess the sensitivity and specificity of
      fluorescence immunocytochemistry (uCyt+ assay) as combined with urinary cytology
      for detection of primary and recurrent urothelial carcinomas. We analyzed 694
      urinary samples from 236 new symptomatic patients and 458 patients followed after
      transurethral resection (TUR) for bladder tumor. Lesions suspicious for cancer at
      cystoscopy were sampled by biopsies or TUR. Sensitivity and specificity of tests
      were calculated using cystoscopy and histopathology, whether or not combined as
      gold standards. In new symptomatic patients, sensitivity of uCyt+ was 40%, 88.2%,
      and 76.7%, whereas that of urinary cytology was 30%, 70.6%, and 83.3%,
      respectively, in G1, G2, and G3 tumors. In follow-up cases, sensitivity of uCyt+
      was 61.9%, 66.7%, and 76.9%, whereas that of urinary cytology was 38.1%, 58.3%,
      and 64.1%, respectively, in G1, G2, and G3 tumors. The combination of uCyt+ and
      urinary cytology significantly increased mean sensitivity in newly diagnosed
      cases (86.4% versus 71.2% with urinary cytology only, p < 0.05), as well as in
      patients followed after TUR (79.3% versus 55.2%, p < 0.001). Specificity of uCyt+
      and urinary cytology was identical in new patients (83.3%) and was 81.9% and
      86.2%, respectively, in patients followed after TUR. In patients with negative
      cystoscopy, positive uCyt+ tests had a strong predictive value for tumor
      recurrence at 1 year (47.0% versus 11.9% in patients with negative assay, p <
      0.01). We conclude that combining uCyt+ with urinary cytology improves the
      detection of urothelial carcinomas as well in patients with symptoms suggesting
      bladder cancer as in those followed after treatment.

PMID- 12808120
TI  - Origin and development of the precursor lesions in experimental pancreatic cancer
      in rats.
AB  - Notwithstanding the importance of understanding how pancreatic ductal
      adenocarcinoma develops, the process remains controversial. A key question is
      whether the cells of origin of the tubular complexes that constitute precursor
      lesions are derived from a single cell type or from multiple types. Suggestions
      that they arise solely from centroacinar cells or ductal cells have been based on
      inference due to their morphologic appearance in tissue from patients or
      investigation of limited numbers of tubular complexes in animal models later in
      the carcinogenic process. The present study establishes clearly that two steps
      are involved; rapid transdifferentiation to produce tubular complexes followed
      later by transformation of the component cells. Animals were killed at intervals
      beginning 1 day after implantation of the carcinogen dimethylbenzanthracene.
      Transdifferentiation of acinar cells to ductal cells does not require cell
      division. Transition of lobules to tubular complexes begins by 2 days after
      implantation of carcinogen. Within 4 days after implantation well-developed
      tubular complexes are present. Islets participate in the process. Ductal
      adenocarcinoma is observed by 1 month after implantation of carcinogen.
      Chymotrypsin and cytokeratin localized by immunocytochemistry indicate acinar and
      ductal cell characteristics. Acino-ductal transdifferentiation persists in
      carcinogen-implanted animals, but not in controls implanted with sodium chloride
      crystals or subjected to sham implantation. The precursor lesions (tubular
      complexes) are formed by the transdifferentiation of acinar cells and to a lesser
      extent islet cells, with the incorporation of the duct cells pre-existing in the
      lobules. Therefore, cells that at one time were acinar cells, islet cells, and
      duct cells, provide the precursor cells for the ductal adenocarcinoma that
      develops from tubular complexes. The results raise the question whether the
      transdifferentiated cells in the tubular complexes of patients with chronic
      pancreatitis are more susceptible to carcinogenic influences, resulting in the
      increased rate of pancreatic cancer.

PMID- 12808121
TI  - Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor
      progression in ovarian carcinoma.
AB  - To clarify the role of small GTPases Rho in the biologic behavior of ovarian
      carcinoma, we first examined the mRNA expression of RhoA, RhoB, and RhoC in
      benign, borderline, and malignant ovarian tumors using RT-PCR and real-time RT
      PCR. The expression and localization of RhoA protein were also analyzed by
      Western blotting and immunohistochemistry. Finally, we examined whether up
      regulation of Rho enhances the invasiveness of ovarian cancer cells in vitro.
      Analysis of mRNA levels of the Rho family genes revealed that levels of both RhoA
      and RhoC were significantly higher in carcinomas than in benign tumors (RhoA, p =
      0.0035; RhoC, p = 0.0006). According to histologic subtype, both RhoA and RhoC
      mRNA levels in serous carcinomas were significantly higher than those in other
      histologic types. With regard to the International Federation of Gynecological
      and Obstetrics stage classification, both of RhoA and RhoC mRNA levels were
      significantly higher in tumors of Stages III+IV than in those of Stages I+II
      (RhoA, p = 0.0200; RhoC, p = 0.0057). In addition, analysis of matched pairs of
      primary and disseminated lesions demonstrated that expression of both RhoA and
      RhoC mRNA was significantly higher in metastatic than in primary tumors.
      Examination of the protein level showed that expression of RhoA was also
      increased in advanced ovarian carcinomas, especially those of serous histology.
      Accordingly, we hypothesized that up-regulation of Rho GTPases plays an important
      role in the progression of ovarian carcinoma. Matrigel invasion assay using the
      ovarian cancer cell line, SKOV3, showed that up-regulation and activation after
      treatment with lysophosphatidic acid was associated with enhanced invasion of the
      cancer cells. This increase in invasiveness was suppressed by the addition of C3,
      a specific inhibitor of Rho. These findings suggest that up-regulation of Rho
      GTPases is important in the tumor progression of ovarian carcinoma and that Rho
      family proteins could be a molecular target in cancer therapy.

PMID- 12808122
TI  - Fibrinolytic balance of the arterial wall: pulmonary artery displays increased
      fibrinolytic potential compared with aorta.
AB  - Classic pulmonary thromboembolism research has documented that large pulmonary
      thromboemboli lyse spontaneously, suggesting potent fibrinolytic activity in
      human pulmonary artery (Pa). This concept conflicts with published animal studies
      in which the proximal Pa was reported to be devoid of tissue plasminogen
      activator (t-PA) expression. The current study used in situ hybridization
      protocols to demonstrate t-PA expression in samples of human main Pa (n = 30).
      Real-time PCR was used to demonstrate quantitatively that the levels of t-PA
      transcripts were higher than those of its primary regulator [ie, plasminogen
      activator-inhibitor 1 (PAI-1)] in the Pa samples. Immunologic and functional
      assays extended these observations by demonstrating that levels of t-PA antigen
      were higher than PAI-1 antigen, which resulted in the detection of free t-PA
      activity. This contrasted with the fibrinolytic balance of matched samples of
      aorta (n = 6) in which PAI-1 transcripts and antigen values were higher than the
      corresponding t-PA values, and only M(r) 110 kDa t-PA-PAI-1 complexes could be
      detected in functional assays. To assess the relative fibrinolytic contribution
      of the endothelial cell layer, Pa endothelial cells and aortic endothelial cells
      were scraped and propagated in culture for 20 +/- 6 days. Pa endothelial cell
      conditioned media revealed increased t-PA/PAI-1 antigen ratios. Taken together,
      our data indicate that the balance between t-PA and PAI-1 is shifted in human
      main Pa to favor net PA activity.

PMID- 12808123
TI  - Establishment and characterization of a continuous human chondrosarcoma cell
      line, ch-2879: comparative histologic and genetic studies with its tumor of
      origin.
AB  - Chondrosarcomas are malignant cartilage-forming tumors that represent the second
      most common malignant solid tumor of bone. These biologically poorly understood
      neoplasms vary considerably in clinical presentation and biologic behavior.
      Chemotherapy and radiation therapy are generally ineffective. Here we describe
      the establishment and characterization of a new human chondrosarcoma cell line
      named ch-2879, and we compare the cell line with its tumor of origin. The cell
      line was established from a recurrent grade 3 chondrosarcoma of the chest wall
      and characterized by growth kinetics and morphologic studies. Immunocytochemistry
      and RT-PCR were performed to examine the expression of cartilage-specific
      phenotypes. Genetic characterization was performed using cytogenetics,
      fluorescence in situ hybridization, flow cytometry, and molecular techniques for
      analysis of the genes implicated in cell cycle control, amplification of MDM2,
      CDK4, and Cyclin D1, and mutations in the p53 gene. ch-2879 cells were
      subcultured for more than 80 passages. They expressed vimentin, HNK-1, HBA-71, Ki
      67, cyclin D1, Fli-1, S-100, p21, p27, and p53 and were negative for cytokeratin,
      EMA, p14, p16, MDM2, Rb, and c-erb-b2 antigens. Cytogenetically the recurrent
      tumor showed a hyperhaploid karyotype with clonal numerical and structural
      abnormalities. The sole structural abnormality was a chromosome derivative of a
      t(1;21) translocation. The cell line at passage 3 showed two populations: the
      hyperhaploid and an exactly duplicated, hypotriploid population. After the 18th
      passage, only the hypotriploid population was present. The cells expressed
      collagen 2. Molecular comparison of the primary and recurrent tumor evidenced an
      in vivo molecular change consisting of a deletion of 9p21 genes in the
      recurrence, probably caused by a selection process. Because of its gene
      expression profile, including expression of genes implicated in chondrogenesis in
      uncoated plastic dishes, this cell line may prove useful for cellular and
      molecular studies as well as studies of chondrosarcoma characterization and
      treatment.

PMID- 12808124
TI  - Zinc-based fixative improves preservation of genomic DNA and proteins in
      histoprocessing of human tissues.
AB  - Advantageous preservation of histology and detailed cellular morphology has
      rendered neutral buffered formalin (NBF) the most widely used fixative in
      clinical pathology. Despite excellent morphology for routine diagnostics, a major
      drawback of NBF fixation is its detrimental effect on DNA and RNA quality. In
      addition to complicating analysis of genes and transcripts in complex tissues,
      NBF denatures proteins and thereby hampers immunohistochemical visualization of
      certain antigens. In the present study, we evaluated a zinc-based fixative (ZBF)
      regarding its effects on tissue morphology, quality of genomic DNA, and
      preservation of protein immunoreactivity in a broad spectrum of tissues. Four
      different modes of fixation were analyzed: ZBF-paraffin embedding, NBF-paraffin
      embedding, ZBF-fixation prior to snap-freezing, and immediate snap-freezing.
      Laser-assisted microdissection, allowing retrieval of a defined number of cells
      for PCR, was used to study DNA quality. Genomic DNA was analyzed using primers
      for beta2-microglobulin and the transferrin receptor. Immunohistochemistry was
      performed using nine antibodies. Tissue microarray blocks were used for analysis
      of morphology and immunoreactivity. Only slight impairment of morphologic
      qualities was found after ZBF-paraffin embedding, whereas ZBF prior to freezing
      resulted in a more crisp morphology compared with routine cryosections. A
      significantly higher DNA yield was observed in samples isolated from ZBF-paraffin
      embedded tissues compared with NBF-paraffin-embedded tissues. Both yield and
      quality of DNA was comparable in frozen tissues irrespective to prior ZBF
      fixation. Immunoreactivity in paraffin-embedded tissue was superior in ZBF
      fixated tissue compared with NBF-fixated for a majority of tested antibodies.
      Furthermore, for seven out of nine antibodies, antigen retrieval pretreatment
      proved unnecessary in ZBF-fixated tissue. Thus, despite a slight impairment of
      morphology, ZBF preserves protein structures well. We conclude that ZBF is
      superior to NBF for analysis of DNA and protein expression. Fixation of tissues
      in ZBF may also be an alternative strategy to freeze storage of tissue specimens,
      eg, in future bio-banks.

PMID- 12808125
TI  - Coxsackievirus and adenovirus receptor, a tight junction membrane protein, is
      expressed in glomerular podocytes in the kidney.
AB  - In nephrosis, filtration slits of podocytes are greatly narrowed, and slit
      diaphragms are displaced by junctions with close contact. Freeze-fracture studies
      have shown that the newly formed junctions consist of tight junctions and gap
      junctions. Several tight-junction proteins are known as integral membrane
      components, including occludin and claudins; but none of them have been found in
      podocytes. Coxsackievirus and adenovirus receptor (CAR) has recently been
      identified as a virus receptor that is a 46-kDa integral membrane protein with
      two Ig-like domains in the extracellular region. In polarized epithelial cells,
      CAR is expressed at the tight junction, where it associates with ZO-1 and plays a
      role in the barrier to the movement of macromolecules and ions. In the present
      study, we investigated the expression and localization of CAR in rat kidneys
      treated with puromycin aminonucleoside (PAN) and in rat kidneys perfused for 15
      minutes with protamine sulfate (PS). Both the experimental models have been used
      to induce tight junctions in podocytes. Ribonuclease protection assay and Western
      blot analysis revealed a distinct increase of CAR transcript and protein in
      glomeruli during PAN nephrosis but no increase in glomeruli by PS perfusion.
      Immunohistochemistry revealed a significant increase in CAR staining intensity
      along the glomerular capillary wall in PAN nephrosis and after PS perfusion.
      Immunoelectron microscopy demonstrated in both the models that the immunogold
      particles for CAR along the capillary wall were found predominantly at close cell
      cell contact sites of podocytes but were rarely found at slit diaphragms. In
      cultured podocytes, CAR was localized at cell-cell contact sites. CAR
      distribution was identical to that of ZO-1 and different from that of a gap
      junction protein, connexin43. These findings indicate that CAR is an integral
      membrane component of tight junction in podocytes and that CAR expression in
      podocytes is regulated at the transcriptional level and in the redistribution of
      protein.

PMID- 12808126
TI  - Establishment and characterization by gene expression profiling of a new diffuse
      large B-cell lymphoma cell line, EJ-1, carrying t(14;18) and t(8;14)
      translocations.

PMID- 12808127
TI  - Percutaneous tumor ablation: reduced tumor growth with combined radio-frequency
      ablation and liposomal doxorubicin in a rat breast tumor model.
AB  - PURPOSE: To determine whether combined intravenous liposomal doxorubicin and
      radio-frequency (RF) ablation decreases tumor growth and increases endpoint
      survival over those with RF or liposomal doxorubicin alone in an animal tumor
      model. MATERIALS AND METHODS: Subcutaneous R3230 mammary adenocarcinoma (1.1-1.4
      cm) was implanted in female Fischer rats. Initially, 35 tumors were randomized
      into four experimental groups: (a) conventional monopolar RF (70 degrees C for 5
      minutes) alone, (b) liposomal doxorubicin (1 mg) alone, (c) RF ablation followed
      by liposomal doxorubicin, and (d) no treatment. Ten additional tumors were
      randomized into two groups that received a 90 degrees C RF dose either with or
      without liposomal doxorubicin. Tumor growth rates and the defined survival
      endpoint, the time at which the tumor reached 3.0 cm in diameter, were recorded.
      The effect of treatments on endpoint survival and tumor doubling time were
      analyzed by means of the Kaplan-Meier method and analysis of variance statistics.
      RESULTS: Differences in endpoint survival and tumor doubling time in the six
      groups were highly significant (P <.001). Endpoint survivals were 9.1 days +/-
      2.5 for the control group, 16 days +/- 3.7 for tumors treated with 70 degrees C
      RF alone, 16.5 days +/- 3.2 for tumors treated with liposomal doxorubicin alone,
      and 26.6 +/- 5.3 days with combined treatment. For 90 degrees C RF ablation,
      endpoint survivals were 16.6 days +/- 1.2 and 31.5 days +/- 3.0 without and with
      liposomal doxorubicin (P <.01). Mean endpoint survival and tumor doubling times
      for the three RF levels (0, 70 degrees C, and 90 degrees C) were all
      significantly different (P =.01). Additionally, animals that received combined
      liposomal doxorubicin and 90 degrees C RF ablation survived longer than did
      animals that received combined liposomal doxorubicin and 70 degrees C RF ablation
      (P <.01). CONCLUSION: Combined RF ablation and liposomal doxorubicin retards
      tumor growth and may increase animal survival compared with that with either
      therapy alone or no therapy.

PMID- 12808128
TI  - Structural determinant of TRPV1 desensitization interacts with calmodulin.
AB  - The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel
      that serves as a polymodal detector of pain-producing chemical and physical
      stimuli. Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch
      clamp experiments when using both heterologous expression systems and native
      sensory ganglia is thought to be one mechanism underlying the paradoxical
      effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca2+
      binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1,
      and that disruption of the calmodulin-binding segment prevents TRPV1
      desensitization. Compounds that interfere with the 35-aa segment could therefore
      prove useful in the treatment of pain.

PMID- 12808129
TI  - Single-molecule detection of DNA hybridization.
AB  - We demonstrate the detection of nanometer-scale conformational changes of single
      DNA oligomers through a micromechanical technique. The quantity monitored is the
      displacement of a micrometer-size bead tethered to a surface by the probe
      molecule undergoing the conformational change. This technique allows probing of
      conformational changes within distances beyond the range of fluorescence
      resonance energy transfer. We apply the method to detect single hybridization
      events of label-free target oligomers. Hybridization of the target is detected
      through the conformational change of the probe.

PMID- 12808130
TI  - Inducible nitric oxide synthase expression inhibition by adenovirus E1A.
AB  - Nitric oxide (NO) is an antiviral effector of the innate immune system. Viruses
      that can interfere with NO synthesis may be able to replicate more rapidly than
      viruses that cannot limit NO synthesis. We show that the adenovirus E1A protein
      inhibits NO production by decreasing expression of the inducible NO synthase
      (NOS2). The amino-terminal portion of E1A decreases transactivation of the NOS2
      5'-flanking region, limiting the DNA binding activity of NF-kappaB and inhibiting
      NOS2 expression. E1A is thus able to deactivate a critical component of the host
      defense against viral infection. Viral inhibition of NO production is a mechanism
      that may enable certain viruses to evade the host innate immune system.

PMID- 12808131
TI  - A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells.
AB  - Overexpression of c-Myc is one of the most common alterations in human cancers,
      yet it is not clear how this transcription factor acts to promote malignant
      transformation. To understand the molecular targets of c-Myc function, we have
      used an unbiased genome-wide location-analysis approach to examine the genomic
      binding sites of c-Myc in Burkitt's lymphoma cells. We find that c-Myc together
      with its heterodimeric partner, Max, occupy >15% of gene promoters tested in
      these cancer cells. The DNA binding of c-Myc and Max correlates extensively with
      gene expression throughout the genome, a hallmark attribute of general
      transcription factors. The c-Myc/Max heterodimer complexes also colocalize with
      transcription factor IID in these cells, further supporting a general role for
      overexpressed c-Myc in global gene regulation. In addition, transcription of a
      majority of c-Myc target genes exhibits changes correlated with levels of c-myc
      mRNA in a diverse set of tissues and cell lines, supporting the conclusion that c
      Myc regulates them. Taken together, these results suggest a general role for
      overexpressed c-Myc in global transcriptional regulation in some cancer cells and
      point toward molecular mechanisms for c-Myc function in malignant transformation.

PMID- 12808132
TI  - Recombinant lymphocytic choriomeningitis virus expressing vesicular stomatitis
      virus glycoprotein.
AB  - A recombinant S segment RNA (Sr) of the prototypic arenavirus lymphocytic
      choriomeningitis virus (LCMV) where the glycoprotein of vesicular stomatitis
      virus (VSVG) was substituted for the glycoprotein of LCMV (LCMV-GP) was produced
      intracellularly from cDNA under the control of a polymerase I promoter.
      Coexpression of the LCMV proteins NP and L allowed expression of VSVG from Sr.
      Infection of transfected cells with WT LCMV (LCMVwt) resulted in reassortment of
      the L segment of LCMVwt with the Sr at low frequency. Isolation of recombinant
      LCMV (rLCMV) expressing VSVG (rLCMV/VSVG) was achieved by selection against
      LCMVwt by using a cell line deficient in the cellular protease S1P. This approach
      was based on the finding that processing of LCMV-GP by S1P was required for virus
      infectivity. Characterization of protein and RNA expression of rLCMV/VSVG in
      infected cells confirmed the expected virus genome organization. rLCMV/VSVG
      caused syncytium formation in cultured cells and grew to approximately 100-fold
      lower titers than WT virus but, like the parent virus, it persisted in neonatally
      infected mice without clinical signs of disease.

PMID- 12808133
TI  - Targeted cytosine methylation for in vivo detection of protein-DNA interactions.
AB  - We report a technique, named targeted gene methylation (TAGM), for identifying in
      vivo protein-binding sites in chromatin. M.CviPI, a cytosine-5 DNA
      methyltransferase recognizing GC sites, is fused to a DNA-binding factor enabling
      simultaneous detection of targeted methylation, factor footprints, and chromatin
      structural changes by bisulfite genomic sequencing. Using TAGM with the yeast
      transactivator Pho4, methylation enrichments of up to 34- fold occur proximal to
      native Pho4-binding sites. Additionally, significant selective targeting of
      methylation is observed several hundred nucleotides away, suggesting the
      detection of long-range interactions due to higher-order chromatin structure. In
      contrast, at an extragenic locus lacking Pho4-binding sites, methylation levels
      are at the detection limit at early times after Pho4 transactivation. Notably,
      substantial amounts of methylation are targeted by Pho4-M.CviPI under repressive
      conditions when most of the transactivator is excluded from the nucleus. Thus,
      TAGM enables rapid detection of DNA-protein interactions even at low occupancies
      and has potential for identifying factor targets at the genome-wide level.
      Extension of TAGM from yeast to vertebrates, which use methylation to initiate
      and propagate repressed chromatin, could also provide a valuable strategy for
      heritable inactivation of gene expression.

PMID- 12808134
TI  - Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA
      mediated gene silencing.
AB  - Glucose homeostasis is controlled by insulin in part through the translocation of
      intracellular glucose transporter 4 to the plasma membrane in muscle and fat
      cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been
      implicated in this insulin-signaling pathway, but results with a variety of
      reagents including Akt1-/- and Akt2-/- mice have been equivocal. Here we report
      the application of small interfering RNA-directed gene silencing to deplete both
      Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired
      insulin-mediated hexose transport activity but had no detectable effect on
      glycogen synthase kinase (GSK)-3 phosphorylation. In contrast, depletion of Akt2
      alone by 70% inhibited approximately half of the insulin responsiveness. Combined
      depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin
      action on glucose transporter 4 movements, hexose transport activity, and GSK-3
      phosphorylation. These data demonstrate a primary role of Akt2 in insulin
      signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this
      pathway, and an absolute requirement of Akt protein kinases for regulation of
      glucose transport and GSK-3 in cultured adipocytes.

PMID- 12808135
TI  - Prediction and measurement of an autoregulatory genetic module.
AB  - The deduction of phenotypic cellular responses from the structure and behavior of
      complex gene regulatory networks is one of the defining challenges of systems
      biology. This goal will require a quantitative understanding of the modular
      components that constitute such networks. We pursued an integrated approach,
      combining theory and experiment, to analyze and describe the dynamics of an
      isolated genetic module, an in vivo autoregulatory gene network. As predicted by
      the model, temperature-induced protein destabilization led to the existence of
      two expression states, thus elucidating the trademark bistability of the positive
      feedback-network architecture. After sweeping the temperature, observed
      population distributions and coefficients of variation were in quantitative
      agreement with those predicted by a stochastic version of the model. Because
      model fluctuations originated from small molecule-number effects, the
      experimental validation underscores the importance of internal noise in gene
      expression. This work demonstrates that isolated gene networks, coupled with
      proper quantitative descriptions, can elucidate key properties of functional
      genetic modules. Such an approach could lead to the modular dissection of
      naturally occurring gene regulatory networks, the deduction of cellular processes
      such as differentiation, and the development of engineered cellular control.

PMID- 12808136
TI  - Effect of insulin on human skeletal muscle mitochondrial ATP production, protein
      synthesis, and mRNA transcripts.
AB  - Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP
      production. Although insulin is a major regulator of fuel metabolism, its effect
      on mitochondrial ATP production is not known. Here we report increases in vastus
      lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans
      (P < 0.01) i.v. infused with insulin (1.5 milliunits/kg of fat-free mass per min)
      while clamping glucose, amino acids, glucagon, and growth hormone. Increased ATP
      production occurred in association with increased mRNA levels from both
      mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase
      (COX) subunit IV] genes (164-180%) encoding mitochondrial proteins (P < 0.05). In
      addition, muscle mitochondrial protein synthesis, and COX and citrate synthase
      enzyme activities were increased by insulin (P < 0.05). Further studies
      demonstrated no effect of low to high insulin levels on muscle mitochondrial ATP
      production for people with type 2 diabetes mellitus, whereas matched nondiabetic
      controls increased 16-26% (P < 0.02) when four different substrate combinations
      were used. In conclusion, insulin stimulates mitochondrial oxidative
      phosphorylation in skeletal muscle along with synthesis of gene transcripts and
      mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic
      patients has a reduced capacity to increase ATP production with high insulin
      levels.

PMID- 12808137
TI  - Social interaction shapes babbling: testing parallels between birdsong and
      speech.
AB  - Birdsong is considered a model of human speech development at behavioral and
      neural levels. Few direct tests of the proposed analogs exist, however. Here we
      test a mechanism of phonological development in human infants that is based on
      social shaping, a selective learning process first documented in songbirds. By
      manipulating mothers' reactions to their 8-month-old infants' vocalizations, we
      demonstrate that phonological features of babbling are sensitive to nonimitative
      social stimulation. Contingent, but not noncontingent, maternal behavior
      facilitates more complex and mature vocal behavior. Changes in vocalizations
      persist after the manipulation. The data show that human infants use social
      feedback, facilitating immediate transitions in vocal behavior. Social
      interaction creates rapid shifts to developmentally more advanced sounds. These
      transitions mirror the normal development of speech, supporting the predictions
      of the avian social shaping model. These data provide strong support for a
      parallel in function between vocal precursors of songbirds and infants. Because
      imitation is usually considered the mechanism for vocal learning in both taxa,
      the findings introduce social shaping as a general process underlying the
      development of speech and song.

PMID- 12808138
TI  - Small nucleolar RNA interference induced by antisense or double-stranded RNA in
      trypanosomatids.
AB  - In trypanosomes the C/D- and H/ACA-like small nucleolar RNAs (snoRNAs) are
      clustered and repeated in the genome. The snoRNAs studied to date are transcribed
      as polycistronic transcripts by RNA polymerase II and then processed, resulting
      in mature snoRNAs. In this study we demonstrated that snoRNA genes can be
      silenced in three trypanosomatid species: Leptomonas collosoma, Leishmania major,
      and Trypanosoma brucei. Silencing was achieved in L. collosoma and L. major by
      the expressing of an antisense transcript complementary to the snoRNA gene and
      was accompanied by the accumulation of small interfering RNA. Silencing
      eliminated the mature snoRNA but not its precursor and abolished the specific 2'
      O-methylation guided by the snoRNA. In T. brucei, silencing was achieved by using
      the inducible synthesis of double-stranded RNA from T7 opposing promoters.
      Silencing varied between the different snoRNA genes, which may reflect the
      accessibility of small interfering RNA to the target RNAs. This study suggests
      that RNA interference can degrade snoRNAs. This study has further implications in
      elucidating the function of nucleolar RNAs and specific modifications guided by
      these RNAs in trypanosomatids and perhaps in other eukaryotes as well.

PMID- 12808139
TI  - From latent disseminated cells to overt metastasis: genetic analysis of systemic
      breast cancer progression.
AB  - According to the present view, metastasis marks the end in a sequence of genomic
      changes underlying the progression of an epithelial cell to a lethal cancer.
      Here, we aimed to find out at what stage of tumor development transformed cells
      leave the primary tumor and whether a defined genotype corresponds to metastatic
      disease. To this end, we isolated single disseminated cancer cells from bone
      marrow of breast cancer patients and performed single-cell comparative genomic
      hybridization. We analyzed disseminated tumor cells from patients after curative
      resection of the primary tumor (stage M0), as presumptive progenitors of manifest
      metastasis, and from patients with manifest metastasis (stage M1). Their genomic
      data were compared with those from microdissected areas of matched primary
      tumors. Disseminated cells from M0-stage patients displayed significantly fewer
      chromosomal aberrations than primary tumors or cells from M1-stage patients (P <
      0.008 and P < 0.0001, respectively), and their aberrations appeared to be
      randomly generated. In contrast, primary tumors and M1 cells harbored different
      and characteristic chromosomal imbalances. Moreover, applying machine-learning
      methods for the classification of the genotypes, we could correctly identify the
      presence or absence of metastatic disease in a patient on the basis of a single
      cell genome. We suggest that in breast cancer, tumor cells may disseminate in a
      far less progressed genomic state than previously thought, and that they acquire
      genomic aberrations typical of metastatic cells thereafter. Thus, our data
      challenge the widely held view that the precursors of metastasis are derived from
      the most advanced clone within the primary tumor.

PMID- 12808140
TI  - Differential effects of ethanol antagonism and neuroprotection in peptide
      fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity.
AB  - NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent
      neuroprotective protein, is protective at femtomolar concentrations against a
      wide array of neural insults and prevents ethanol-induced fetal wastage and
      growth retardation in mice. NAP also antagonizes ethanol inhibition of L1
      mediated cell adhesion (ethanol antagonism). We performed an Ala scanning
      substitution of NAP to determine the role of ethanol antagonism and
      neuroprotection in NAP prevention of ethanol embryotoxicity. The Ser-Ile-Pro
      region of NAP was crucial for both ethanol antagonism and protection of cortical
      neurons from tetrodotoxin toxicity (neuroprotection). Ala replacement of either
      Ser-5 or Pro-7 (P7A-NAP) abolished NAP neuroprotection but minimally changed the
      efficacy of NAP ethanol antagonism. In contrast, Ala replacement of Ile-6 (I6A
      NAP) caused a decrease in potency (>2 logarithmic orders) with only a small
      reduction (<10%) in the efficacy of NAP neuroprotection but markedly reduced the
      efficacy (50%) and the potency (5 logarithmic orders) of NAP ethanol antagonism.
      Ethanol significantly reduced the number of paired somites in mouse whole-embryo
      culture; this effect was prevented significantly by 100 pM NAP or by 100 pM P7A
      NAP, but not by 100 pM I6A-NAP. The structure-activity relation for NAP
      prevention of ethanol embryotoxicity was similar to that for NAP ethanol
      antagonism and different from that for NAP neuroprotection. These findings
      support the hypothesis that NAP antagonism of ethanol inhibition of L1 adhesion
      plays a central role in NAP prevention of ethanol embryotoxicity and highlight
      the potential importance of ethanol effects on L1 in the pathophysiology of fetal
      alcohol syndrome.

PMID- 12808141
TI  - Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2.
AB  - Mice lacking the chemokine receptor chemotactic cytokine receptor 2 (CCR2) have a
      marked attenuation of monocyte recruitment in response to various inflammatory
      stimuli and a reduction of inflammatory lesions in models of demyelinating
      disease. In the present study, we compared nociceptive responses in inflammatory
      and neuropathic models of pain in CCR2 knockout and wild-type mice. In acute pain
      tests, responses were equivalent in CCR2 knockout and wild-type mice. In models
      of inflammatory pain, CCR2 knockout mice showed a 70% reduction in phase 2 of the
      intraplantar formalin-evoked pain response but only a modest (20-30%) and
      nonsignificant reduction of mechanical allodynia after intraplantar Freund's
      adjuvant (CFA). In a model of neuropathic pain, the development of mechanical
      allodynia was totally abrogated in CCR2 knockout mice. CFA administration induced
      marked up-regulation of CCR2 mRNA in the skin and a moderate increase in the
      sciatic nerve and dorsal root ganglia (DRG). In response to nerve ligation,
      persistent and marked up-regulation of CCR2 mRNA was evident in the nerve and
      DRG. Disruption of Schwann cells in response to nerve lesion resulted in
      infiltration of CCR2-positive monocytes/macrophages not only to the neuroma but
      also to the DRG. Chronic pain also resulted in the appearance of activated CCR2
      positive microglia in the spinal cord. Collectively, these data suggest that the
      recruitment and activation of macrophages and microglia peripherally and in
      neural tissue may contribute to both inflammatory and neuropathic pain states.
      Accordingly, blockade of the CCR2 receptor may provide a novel therapeutic
      modality for the treatment of chronic pain.

PMID- 12808142
TI  - Understanding folding and design: replica-exchange simulations of "Trp-cage"
      miniproteins.
AB  - Replica-exchange molecular dynamics simulations in implicit solvent have been
      carried out to study the folding thermodynamics of a designed 20-residue peptide,
      or "miniprotein." The simulations in this study used the amber (parm94) force
      field along with the generalized Born/solvent-accessible surface area implicit
      solvent model, and they spanned a range of temperatures from 273 to 630 K.
      Starting from a completely extended initial conformation, simulations of one
      peptide sequence sample conformations that are <1.0 A Calpha rms positional
      deviation from structures in the corresponding NMR ensemble. These folded states
      are thermodynamically stable with a simulated melting temperature of
      approximately 400 K, and they satisfy the majority of experimentally observed NMR
      restraints. Simulations of a related mutant peptide show a degenerate ensemble of
      states at low temperature, in agreement with experimental results.

PMID- 12808143
TI  - Crystal structure of the SOS cell division inhibitor SulA and in complex with
      FtsZ.
AB  - SulA halts cell division in Escherichia coli by binding to the major component of
      the division machinery FtsZ. We have solved the crystal structure of SulA alone
      and in complex with FtsZ from Pseudomonas aeruginosa. SulA is expressed when the
      SOS response is induced. This is a mechanism to inhibit cell division and repair
      DNA in the event of DNA damage. FtsZ is a tubulin-like protein that forms
      polymers, with the active-site GTPase split across two monomers. One monomer
      provides the GTP-binding site and the other, through its T7 loop nucleotide
      hydrolysis. Our structures show that SulA is a dimer, and that SulA inhibits cell
      division neither by binding the nucleotide-binding site nor by inducing
      conformational changes in FtsZ. Instead, SulA binds the T7 loop surface of FtsZ,
      opposite the nucleotide-binding site, blocking polymer formation. These findings
      explain why GTP hydrolysis and polymer turnover are required for SulA inhibition.

PMID- 12808144
TI  - Mdm20 protein functions with Nat3 protein to acetylate Tpm1 protein and regulate
      tropomyosin-actin interactions in budding yeast.
AB  - The evolutionarily conserved Mdm20 protein (Mdm20p) plays an important role in
      tropomyosin-F-actin interactions that generate actin filaments and cables in
      budding yeast. However, Mdm20p is not a structural component of actin filaments
      or cables, and its exact function in cable stability has remained a mystery.
      Here, we show that cells lacking Mdm20p fail to N-terminally acetylate Tpm1p, an
      abundant form of tropomyosin that binds and stabilizes actin filaments and
      cables. The F-actin-binding activity of unacetylated Tpm1p is reduced severely
      relative to the acetylated form. These results are complemented by the recent
      report that Mdm20p copurifies with one of three acetyltransferases in yeast, the
      NatB complex. We present genetic evidence that Mdm20p functions cooperatively
      with Nat3p, the catalytic subunit of the NatB acetyltransferase. These combined
      results strongly suggest that Mdm20p-dependent, N-terminal acetylation of Tpm1p
      by the NatB complex is required for Tpm1p association with, and stabilization of,
      actin filaments and cables.

PMID- 12808145
TI  - Gene function analysis in environmental isolates: the nif regulon of the strict
      iron oxidizing bacterium Leptospirillum ferrooxidans.
AB  - A random genomic library from an environmental isolate of the Gram-negative
      bacterium Leptospirillum ferrooxidans has been printed on a microarray. Gene
      expression analysis was carried out with total RNA extracted from L. ferrooxidans
      cultures in the presence or absence of ammonium as nitrogen source under aerobic
      conditions. Although practically nothing is known about the genome sequence of
      this bacterium, this approach allowed us the selection and sequencing of only
      those clones bearing genes that showed an altered expression pattern. By sequence
      comparison, we have identified most of the genes of nitrogen fixation regulon in
      L. ferrooxidans, like the nifHDKENX operon, encoding the structural components of
      Mo-Fe nitrogenase; nifSU-hesB-hscBA-fdx operon, for Fe-S cluster assembly; the
      amtB gene (ammonium transporter); modA (molybdenum ABC type transporter); some
      regulatory genes like ntrC, nifA (the specific activator of nif genes); or two
      glnB-like genes (encoding the PII regulatory protein). Our results show that
      shotgun DNA microarrays are very powerful tools to accomplish gene expression
      studies with environmental bacteria whose genome sequence is still unknown,
      avoiding the time and effort necessary for whole genome sequencing projects.

PMID- 12808146
TI  - Direct activation of the apoptosis machinery as a mechanism to target cancer
      cells.
AB  - Apoptosis plays a pivotal role in the cytotoxic activity of most chemotherapeutic
      drugs, and defects in this pathway provide a basis for drug resistance in many
      cancers. Thus the ability to restore apoptosis by using small molecules could
      have important therapeutic implications. Using a cell-free assay to
      simultaneously target multiple components of the apoptosis pathway, we identified
      a class of compounds that activate caspases in a cytochrome c-dependent manner
      and induce apoptosis in whole cells. By reconstituting the apoptosis pathway with
      purified proteins, we determined that these compounds promote the protein-protein
      association of Apaf-1 into the functional apoptosome. These compounds exert
      cytostatic and cytotoxic effects on a variety of cancer cell lines while having
      little or no activity against the normal cell lines tested. These findings
      suggest that direct activation of the basic apoptosis machinery may be a viable
      mechanism to selectively target cancer.

PMID- 12808147
TI  - Membrane-binding and activation mechanism of PTEN.
AB  - PTEN is a tumor suppressor that reverses the action of phosphoinositide 3-kinase
      by catalyzing the removal of the 3' phosphate of phosphoinositides. Despite the
      critical role of PTEN in cell signaling and regulation, the mechanisms of its
      membrane recruitment and activation is still poorly understood. PTEN is composed
      of an N-terminal phosphatase domain, a C2 domain, and a C-terminal tail region
      that contains the PSD-95/Dlg/ZO-1 homology (PDZ) domain-binding sequence and
      multiple phosphorylation sites. Our in vitro surface plasmon resonance
      measurements using immobilized vesicles showed that both the phosphatase domain
      and the C2 domain, but not the C-terminal tail, are involved in electrostatic
      membrane binding of PTEN. Furthermore, the phosphorylation-mimicking mutation on
      the C-terminal tail of PTEN caused an approximately 80-fold reduction in its
      membrane affinity, mainly by slowing the membrane-association step. Subcellular
      localization studies of PTEN transfected into HEK293T and HeLa cells indicated
      that targeting of PTEN to the plasma membrane is coupled with rapid degradation
      and that the phosphatase domain and the C2 domain are both necessary and
      sufficient for its membrane recruitment. Results also indicated that the
      phosphorylation regulates the targeting of PTEN to the plasma membrane not by
      blocking the PDZ domain-binding site but by interfering with electrostatic
      membrane binding of PTEN. On the basis of these results, we propose a membrane
      binding and activation mechanism for PTEN, in which the
      phosphorylation/dephosphorylation of the C-terminal region serves as an
      electrostatic switch that controls the membrane translocation of the protein.

PMID- 12808148
TI  - Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic
      syndrome.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disease of
      unknown etiology. Recently, it has been reported that imatinib mesylate
      (Gleevec), an inhibitor of Bcr-Abl kinase useful in the treatment of chronic
      myeloid leukemia, is also effective in treating HES; however, the molecular
      target of imatinib in HES is unknown. This report identifies a genetic
      rearrangement in the eosinophilic cell line EOL-1 that results in the expression
      of a fusion protein comprising an N-terminal region encoded by a gene of unknown
      function with the GenBank accession number NM_030917 and a C-terminal region
      derived from the intracellular domain of the platelet-derived growth factor
      receptor alpha (PDGFRalpha). The fusion gene was also detected in blood cells
      from two patients with HES. We propose naming NM_030917 Rhe for Rearranged in
      hypereosinophilia. Rhe-PDGFRalpha fusions result from an apparent interstitial
      deletion that links Rhe to exon 12 of PDGFRalpha on chromosome 4q12. The fusion
      kinase Rhe-PDGFRalpha is constitutively phosphorylated and supports IL-3
      independent growth when expressed in BaF3 cells. Proliferation and viability of
      EOL-1 and BaF3 cells expressing Rhe-PDGFRalpha are ablated by the PDGFRalpha
      inhibitors imatinib, vatalanib, and THRX-165724.

PMID- 12808149
TI  - Comparative genomics of Physcomitrella patens gametophytic transcriptome and
      Arabidopsis thaliana: implication for land plant evolution.
AB  - The mosses and flowering plants diverged >400 million years ago. The mosses have
      haploid-dominant life cycles, whereas the flowering plants are diploid-dominant.
      The common ancestors of land plants have been inferred to be haploid-dominant,
      suggesting that genes used in the diploid body of flowering plants were recruited
      from the genes used in the haploid body of the ancestors during the evolution of
      land plants. To assess this evolutionary hypothesis, we constructed an EST
      library of the moss Physcomitrella patens, and compared the moss transcriptome to
      the genome of Arabidopsis thaliana. We constructed full-length enriched cDNA
      libraries from auxin-treated, cytokinin-treated, and untreated gametophytes of P.
      patens, and sequenced both ends of >40,000 clones. These data, together with the
      mRNA sequences in the public databases, were assembled into 15,883 putative
      transcripts. Sequence comparisons of A. thaliana and P. patens showed that at
      least 66% of the A. thaliana genes had homologues in P. patens. Comparison of the
      P. patens putative transcripts with all known proteins, revealed 9,907 putative
      transcripts with high levels of similarity to vascular plant genes, and 850
      putative transcripts with high levels of similarity to other organisms. The
      haploid transcriptome of P. patens appears to be quite similar to the A. thaliana
      genome, supporting the evolutionary hypothesis. Our study also revealed that a
      number of genes are moss specific and were lost in the flowering plant lineage.

PMID- 12808152
TI  - The evolution of vertebrate blood coagulation as viewed from a comparison of
      puffer fish and sea squirt genomes.
AB  - The blood coagulation scheme for the puffer fish, Fugu rubripes, has been
      reconstructed on the basis of orthologs of genes for mammalian blood clotting
      factors being present in its genome. As expected, clotting follows the same
      fundamental pattern as has been observed in other vertebrates, even though genes
      for some clotting factors found in mammals are absent and some others are present
      in more than one gene copy. All told, 26 different proteins involved in clotting
      or fibrinolysis were searched against the puffer fish genome. Of these, orthologs
      were found for 21. Genes for the "contact system" factors (factor XI, factor XII,
      and prekallikrein) could not be identified. On the other hand, two genes were
      found for factor IX and four for factor VII. It was evident that not all four
      factor VII genes are functional, essential active-site residues having been
      replaced in two of them. A search of the genome of a urochordate, the sea squirt,
      Ciona intestinalis, did not turn up any genuine orthologs for these 26 factors,
      although paralogs and/or constituent domains were evident for virtually all of
      them.

PMID- 12808153
TI  - Modeling of DNA microarray data by using physical properties of hybridization.
AB  - A method of analyzing DNA microarray data based on the physical modeling of
      hybridization is presented. We demonstrate, in experimental data, a correlation
      between observed hybridization intensity and calculated free energy of
      hybridization. Then, combining hybridization rate equations, calculated free
      energies of hybridization, and microarray data for known target concentrations,
      we construct an algorithm to compute transcript concentration levels from
      microarray data. We also develop a method for eliminating outlying data points
      identified by our algorithm. We test the efficacy of these methods by comparing
      our results with an existing statistical algorithm, as well as by performing a
      cross-validation test on our model.

PMID- 12808154
TI  - The thrombospondin 1-TGF-beta axis in fibrotic renal disease.

PMID- 12808150
TI  - Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal
      muscle fiber types and is regulated by calcineurin/NFAT signaling.
AB  - Utrophin levels have recently been shown to be more abundant in slow vs. fast
      muscles, but the nature of the molecular events underlying this difference
      remains to be fully elucidated. Here, we determined whether this difference is
      due to the expression of utrophin A or B, and examined whether transcriptional
      regulatory mechanisms are also involved. Immunofluorescence experiments revealed
      that slower fibers contain significantly more utrophin A in extrasynaptic regions
      as compared with fast fibers. Single-fiber RT-PCR analysis demonstrated that
      expression of utrophin A transcripts correlates with the oxidative capacity of
      muscle fibers, with cells expressing myosin heavy chain I and IIa demonstrating
      the highest levels. Functional muscle overload, which stimulates expression of a
      slower, more oxidative phenotype, induced a significant increase in utrophin A
      mRNA levels. Because calcineurin has been implicated in controlling this slower,
      high oxidative myofiber program, we examined expression of utrophin A transcripts
      in muscles having altered calcineurin activity. Calcineurin inhibition resulted
      in an 80% decrease in utrophin A mRNA levels. Conversely, muscles from transgenic
      mice expressing an active form of calcineurin displayed higher levels of utrophin
      A transcripts. Electrophoretic mobility shift and supershift assays revealed the
      presence of a nuclear factor of activated T cells (NFAT) binding site in the
      utrophin A promoter. Transfection and direct gene transfer studies showed that
      active forms of calcineurin or nuclear NFATc1 transactivate the utrophin A
      promoter. Together, these results indicate that expression of utrophin A is
      related to the oxidative capacity of muscle fibers, and implicate calcineurin and
      its effector NFAT in this mechanism.

PMID- 12808155
TI  - Functional changes in the ageing kidney: is there a role for asymmetric
      dimethylarginine?

PMID- 12808151
TI  - Transforming growth factor beta signaling impairs Neu-induced mammary
      tumorigenesis while promoting pulmonary metastasis.
AB  - The influence of transforming growth factor beta (TGF-beta) signaling on Neu
      induced mammary tumorigenesis and metastasis was examined with transgenic mouse
      models. We generated mice expressing an activated TGF-beta type I receptor or
      dominant negative TGF-beta type II receptor under control of the mouse mammary
      tumor virus promoter. When crossed with mice expressing activated forms of the
      Neu receptor tyrosine kinase that selectively couple to the Grb2 or Shc signaling
      pathways the activated type I receptor increased the latency of mammary tumor
      formation but also enhanced the frequency of extravascular lung metastasis.
      Conversely, expression of the dominant negative type II receptor decreased the
      latency of Neu-induced mammary tumor formation while significantly reducing the
      incidence of extravascular lung metastases. These observations argue that TGF
      beta can promote the formation of lung metastases while impairing Neu-induced
      tumor growth and suggest that extravasation of breast cancer cells from pulmonary
      vessels is a point of action of TGF-beta in the metastatic process.

PMID- 12808156
TI  - Is it really good to be fat on dialysis?

PMID- 12808157
TI  - Diagnosis of renal artery stenosis with magnetic resonance angiography: update
      2003.

PMID- 12808158
TI  - Immunogenicity of therapeutic proteins.

PMID- 12808159
TI  - Recurrent glomerulonephritis following renal transplantation: an update.

PMID- 12808160
TI  - Are the total exchangeable sodium, total exchangeable potassium and total body
      water the only determinants of the plasma water sodium concentration?

PMID- 12808161
TI  - Oxidative stress in end-stage renal disease: an emerging threat to patient
      outcome.
AB  - INTRODUCTION: Patients affected by end-stage renal disease (ESRD) experience an
      excess of morbidity and mortality due to cardiovascular disease (CVD), which
      cannot be fully explained by the classical CVD risk factors. Among emerging CVD
      risk factors, oxidative stress is currently being given emphasis. METHODS: We
      achieved a consensus on key points relating to oxidative stress in ESRD patients.
      RESULTS: ESRD patients are subjected to enhanced oxidative stress, as a result of
      reduced anti-oxidant systems (vitamin C and selenium deficiency, reduced
      intracellular levels of vitamin E, reduced activity of the glutathione system)
      and increased pro-oxidant activity (advanced age, high frequency of diabetes,
      chronic inflammatory state, uraemic syndrome, bio-incompatibility of dialysis
      membranes and solutions). Oxidative stress and inflammation are deeply inter
      related, as different oxidant free radicals are generated by phagocytic cells in
      response to inflammatory stimuli: both are related to endothelial dysfunction, as
      the endothelium is a source and a target of oxidants and participates in the
      inflammatory response. There is growing evidence, from experimental and clinical
      studies, that oxidative stress may be implicated in the pathogenesis of
      atherosclerosis and other complications of ESRD, namely dialysis-related
      amyloidosis, malnutrition and anaemia. Given that free radicals have very short
      half-lives (seconds), the clinical assessment of oxidative stress is based on the
      measurement of different stable oxidized compounds (such as lipid peroxidation
      products, advanced glycation and oxidation lipid and protein products, nucleic
      acid oxidation derivatives) or antibodies directed against oxidized epitopes
      (such as anti-oxidized low-density lipoprotein antibodies). At the same time,
      both enzymatic anti-oxidants (superoxide dismutase, catalase, glutathione
      peroxidase) and non-enzymatic anti-oxidants (glutathione, vitamin C, vitamin E,
      negative inflammatory proteins) can be evaluated. However, many laboratory
      methods assessing various oxidative stress components still have to be
      standardized. Moreover, it is still uncertain whether it is better measuring
      plasma and/or intracellular concentrations or activities of these components. The
      possibility of improving patient outcome by therapeutic interventions aimed at
      reducing oxidative stress, e.g. by vitamin C or vitamin E supplementation,
      currently is to the fore, but results so far have remained inconclusive.
      CONCLUSIONS: It is important to consider oxidative stress as a potentially
      important source of patient morbidity and mortality, although this knowledge is
      not yet immediately applicable in the clinical arena. Further well-designed,
      randomized controlled clinical trials with anti-oxidants (e.g. vitamin E, vitamin
      C, N-acetyl cysteine, L-arginine) are required to establish evidence-based
      recommendations for clinical practice.

PMID- 12808162
TI  - Milk or albumin? The history of proteinuria before Richard Bright.

PMID- 12808163
TI  - Vascular endothelial growth factor expression and glomerular endothelial cell
      loss in the remnant kidney model.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is constitutively expressed
      in the glomerulus where it may have a role in the maintenance of capillary
      endothelial cell integrity. The present study sought to examine changes in VEGF
      expression in a model of progressive renal disease and to assess the effects of
      angiotensin converting enzyme (ACE) inhibition. METHODS: Subtotal nephrectomized
      (STNx) rats were randomly assigned to receive vehicle (n=10) or the ACE inhibitor
      perindopril (8 mg/l drinking water) for 12 weeks duration (n=10). Sham-operated
      rats were used as controls (n=10). Glomerular capillary endothelial cell density
      was evaluated by immunostaining for the pan-endothelial cell marker RECA-1 and
      VEGF expression was assessed by quantitative in situ hybridization. RESULTS: In
      STNx rats glomerular capillary endothelial cell density was reduced to 19% that
      of sham rats (P<0.01) with a concomitant reduction in glomerular VEGF expression,
      also to 19% of sham rats (P<0.01). Perindopril treatment was associated with
      normalization of both capillary endothelial cell density and glomerular VEGF
      mRNA. CONCLUSIONS: Reduction in glomerular VEGF expression is a feature of the
      renal pathology that follows subtotal nephrectomy. In the context of the known
      functions of this growth factor, these findings suggest that diminution in VEGF
      may contribute to the demonstrated loss of glomerular endothelium that develops
      in this model of progressive renal disease.

PMID- 12808164
TI  - Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys
      obesus (sand rat).
AB  - BACKGROUND: Diabetic nephropathy is caused by multiple factors related to the
      altered metabolic environment in diabetes mellitus (DM). Experimental diabetic
      kidney disease is characterized by renal hypertrophy associated with increased
      tissue concentrations of insulin-like growth factor I (IGF-I). To assess the
      specific roles of serum insulin and glucose in mediating the development of
      diabetic nephropathy, the effects of both hyperinsulinaemic and hypoinsulinaemic
      DM were studied in Psammomys obesus (sand rat), a model of type 2 DM. METHODS:
      The IGF-I system was studied in normal Psammomys obesus gerbils and at 5, 15 and
      70 days after the induction of either hyper- or hypoinsulinaemic DM. To induce
      hyperinsulinaemic DM, Psammomys were raised on a high-energy diet.
      Hypoinsulinaemic DM was induced by either administration of streptozotocin or a
      specially designed diet. RESULTS: Hyperinsulinaemic hyperglycaemic Psammomys did
      not exhibit renal hypertrophy (unchanged kidney/body-weight ratio) and renal IGF
      I levels were in the normal range on days 5, 15 and 70. In contrast, Psammomys
      with hypoinsulinaemic hyperglycaemia induced either by streptozotocin injection
      or by pancreas exhaustion brought on by a long-term caloric excess diet, had
      significant increases in kidney/body-weight ratio which were associated with
      elevated renal IGF-I and mRNA and protein levels of kidney IGF binding protein I.
      CONCLUSIONS: This study shows that serum insulin levels in the presence of
      hyperglycaemia have an important role in the development of experimental diabetic
      nephropathy in the Psammomys model. The implication of this finding is that the
      pathophysiological mechanisms for diabetic kidney disease in experimental models
      may be different for type 1 and type 2 DM.

PMID- 12808165
TI  - Urinary excretion of the uraemic toxin p-cresol in the rat: contribution of
      glucuronidation to its metabolization.
AB  - BACKGROUND: Increasing evidence indicates that lipophilic and/or protein-bound
      substances such as p-cresol are responsible for adverse physiological alterations
      in uraemic patients. To better understand the evolution of p-cresol disposition
      in renal failure and dialysis patients, it is necessary to determine its kinetic
      characteristics and biotransformation pathways. METHODS: We studied the
      biotransformation of p-cresol after intravenous injection of the compound in
      eight rats with normal renal function. Urine was collected in four 1 h intervals.
      To evaluate the presence of p-cresol metabolites, beta-glucuronidase was added to
      urine samples and the isolated unidentified chromatographic peak observed in
      previous experiments was submitted to tandem mass spectrometry (MS/MS) analysis.
      RESULTS: Administration of p-cresol produced a p-cresol peak and an unknown peak,
      suggesting biotransformation of the compound. Addition of beta-glucuronidase to
      urine samples and incubation at 37 degrees C resulted in a marked decrease in the
      unidentified peak height (P<0.001) together with an increase in p-cresol peak
      height (P<0.001), suggesting that the unidentified peak was composed, at least in
      part, of p-cresylglucuronide. Mass spectrometry (MS) and MS/MS analysis of the
      isolated unidentified peak confirmed the presence of p-cresylglucuronide. Linear
      regression between the peak height of p-cresylglucuronide before enzyme treatment
      and the increase in p-cresol peak height after enzyme treatment in samples
      incubated with beta-glucuronidase allowed us to calculate the amount of p
      cresylglucuronide as its p-cresol equivalents. This revealed that 64% of the
      injected p-cresol was excreted as glucuronide. There was no change in peak
      heights when sulphatase was added to the urine. When p-cresol and p
      cresylglucuronide levels were combined, approximately 85% of all administered p
      cresol was recovered in the urine. In addition, the combined urinary excretion of
      p-cresol and p-cresylglucuronide was more than four times greater than excretion
      of p-cresol by itself (P<0.01). CONCLUSIONS: In rats with normal renal function,
      intravenous administration of p-cresol results in immediate and extensive
      metabolization of the compound into p-cresylglucuronide. The elimination of p
      cresol from the body depends largely on the urinary excretion of this metabolite.

PMID- 12808166
TI  - Predicted creatinine clearance to evaluate glomerular filtration rate in black
      Caribbean subjects.
AB  - BACKGROUND AND METHODS: Although Caribbean people have been a lesser-studied
      ethnic group than other populations, they have a high burden of hypertension and
      renal disease. Because Caribbean people have a greater muscle mass than
      Caucasians, this study examined the accuracy of creatinine-based estimates
      (creatinine clearance; C(cr) and Cockcroft-Gault formula; C-G Cl) of glomerular
      filtration rate (GFR) in 38 Caribbeans who were matched for age, gender, and GFR,
      with 38 Caucasian subjects. Patients were considered black Caribbean if at least
      one of two parents was of black Caribbean origin. GFR values ranging from 5 to
      140 ml/min/1.73 m(2) were measured by inulin clearance. Results were compared
      using linear correlations and the Bland and Altman methodology to provide better
      estimates of value dispersion. RESULTS: Correlation coefficients between C-G Cl
      and GFR were highly significant in both black Caribbean subjects (r=0.83,
      P<0.001) and Caucasians (r=0.84, P<0.001). Similar coefficients were obtained
      between C(cr) and GFR (r=0.89, P<0.001 and r=0.90, P<0.001, respectively). In
      spite of these strong correlations, the Bland and Altman representation
      highlighted huge intra-individual variations in GFR estimation by C-G Cl and by
      C(cr) in both ethnic groups. The underestimation of GFR by C-G Cl was significant
      in black Caribbeans (-8.6+/-20 ml/min/1.73 m(2), P<0.001) but not in Caucasians (
      5.6+/-20.7 ml/min/1.73 m(2)). C(cr) overestimation of GFR was significant both in
      Caribbeans (8.7+/-16.8 ml/min/1.73 m(2), P<0.001) and in Caucasians (7.2+/-15.7
      ml/min/1.73 m(2), P<0.01). CONCLUSIONS: The C-G formula for estimating GFR yields
      similar clinical values in black Caribbeans and in Caucasians, but the same
      limitations were observed in both ethnic groups.

PMID- 12808167
TI  - Steroid therapy reduces mesangial matrix accumulation in advanced IgA
      nephropathy.
AB  - BACKGROUND: Steroid therapy for IgA nephropathy (IgAN) has been reported to
      ameliorate the long-term prognosis of IgAN, but its mode of action has not been
      fully elucidated. In this study, we examined the effect of steroids on glomerular
      morphological changes in IgAN. METHODS: We examined 16 patients with biopsy
      proven IgAN (male/female =11/5, mean age 32.1 years) who were divided into
      prognosis groups according to criteria set by the Japanese Society of Nephrology.
      Initially, they received a loading dose of steroids, followed by a daily dose of
      10-15 mg prednisolone. After 12 months, they underwent a second biopsy, and their
      histological and clinical features were examined. RESULTS: Before and after
      therapy, systolic blood pressure, diastolic blood pressure, serum creatinine and
      creatinine clearance all remained unchanged. However, urinary protein excretion
      decreased dramatically, from 1.6+/-1.7 to 0.4+/-0.2 g/day (P<0.005). Furthermore,
      computerized imaging revealed a significant reduction of the mesangial matrix
      index (MMI) from 14.5+/-5.2 to 9.5+/-3.6% (P<0.001). The numbers of sclerosing
      glomeruli did not change. CONCLUSIONS: Steroid therapy reduces mesangial matrix
      accumulation and reduces urinary protein excretion in advanced IgAN.

PMID- 12808168
TI  - Idiopathic minimal change nephrotic syndrome in older adults: steroid
      responsiveness and pattern of relapses.
AB  - INTRODUCTION: Minimal change nephrotic syndrome (MCNS) is a common form of
      nephrotic syndrome in children and young adults. We investigated its clinical
      presentations, steroid responsiveness, subsequent clinical course and patterns of
      relapse in older adults in whom it was diagnosed after the age of 50 years.
      METHODS: The clinical records of renal patients followed-up in a single out
      patient clinic were retrieved and those patients with biopsy-proven MCNS were
      included. Patients in the 18-50-year age range (Group A) at the time of biopsy
      were compared with those older than 50 years (Group B) with regard to baseline
      demographic data, clinical features and outcome of treatment. RESULTS: In all, 50
      patients were studied, 35 in Group A (age at diagnosis: 38.8+/-11.91 years) and
      15 in Group B (age at diagnosis: 70+/-6.85 years), with an overall follow-up
      duration of 72.08+/-63.42 months. Group B had a higher prevalence of hypertension
      and lower creatinine clearance at presentation, but the values of creatinine
      clearance for both groups were comparable with age-matched controls. One patient
      from Group B and two from Group A had spontaneous remission. Complete remission
      was achieved in 9.09, 45.45, 90.91 and 100% of Group B patients and 15.63, 62.5,
      87.5 and 93.75% of Group A patients after 2, 4, 8 and 16 weeks of steroid
      therapy, respectively. The median time to complete remission and the duration of
      steroid treatment were similar for both groups. From Group B five patients and 22
      patients from Group A relapsed during follow-up (P=0.055), with similar
      proportions of each group being early relapsers or frequent relapsers. The
      average number of relapses was 2.06 episodes for Group A, compared with 0.87
      episodes for group B (P=0.062). Second agents were used in 20 Group A and four
      Group B patients (P=0.048). Complications of treatment were more common in Group
      A. None of the patients developed doubling of serum creatinine during follow-up.
      CONCLUSIONS: Clinical presentations of older patients with MCNS were similar to
      younger patients apart from the age-related decline of renal function and higher
      prevalence of hypertension. Both groups have similar steroid responsiveness, but
      older patients tend to have fewer relapses and require fewer second agents for
      treatment of relapses.

PMID- 12808169
TI  - Crescentic, proliferative IgA nephropathy: clinical and histological response to
      methylprednisolone and intravenous cyclophosphamide.
AB  - BACKGROUND: IgA nephropathy is an immune-complex glomerulopathy that can result
      in capillary or extra-capillary proliferation. Previous attempts to correlate
      specific histological findings including cellular crescents or endocapillary
      proliferation, with clinical outcomes, have produced conflicting results.
      METHODS: We conducted a prospective open-labelled trial of 12 patients with
      crescentic, proliferative IgA nephropathy and clinically progressive disease and
      treated them with pulse steroids and intravenous cyclophosphamide. Therapy
      included pulse solumedrol at 15 mg/kg/day for 3 days, followed by monthly
      intravenous cyclophosphamide at 0.5 g/m(2) body surface area for 6 months.
      Clinically significant proteinuria (>1.0 g/24 h) was present in all patients,
      while nephrotic-range proteinuria (>3.0 g/24 h) was observed in eight of 12
      patients. All patients were hypertensive (BP >140/90 mmHg). RESULTS: After 6
      months of treatment, the mean serum creatinine was reduced from a maximum of
      2.65+/-0.39 to 1.51+/-0.10 mg/dl (P<0.03), while proteinuria was reduced from
      4.04 to 1.35 g/24 h (P<0.01). The mean slope of 1/serum creatinine increased from
      -0.0398+/-0.02 to 0.0076+/-0.01 after 6 months of therapy, but this trend did not
      reach statistical significance (P<0.08). A repeat kidney biopsy was performed in
      all treated patients. Endocapillary proliferation, cellular crescents and
      karyorrhexis were eliminated in all 12 patients after 6 months of therapy, while
      interstitial fibrosis and tubule dropout remained unchanged. To determine the
      long-term efficacy of the treatment, treated patients were compared to 12
      historical controls matched for severity of IgA on initial biopsy. After 36
      months, the rate of end-stage renal disease in the treated group was lower (1/12)
      than in the historical controls (5/12). CONCLUSIONS: We conclude that steroids
      and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria
      and stabilize renal function in patients with crescentic IgA nephropathy.

PMID- 12808170
TI  - Early referral and planned initiation of dialysis: what impact on quality of
      life?
AB  - BACKGROUND: Early patient referral correlates with improved patient survival on
      dialysis. We examine whether early referral and a planned first dialysis affect
      quality of life (QoL). METHODS: All patients commencing dialysis in nine centres
      in seven European countries between 1 July 1998 and 31 October 1999 were
      recruited. DEFINITIONS: early referral=followed by a nephrologist >1 month before
      first dialysis (<1 month=late referral); planned=early referral and previous
      serum creatinine >300 micro mol/l and non-urgent first dialysis (early referral
      and no creatinine >300 micro mol/l or urgent first dialysis=unplanned). QoL was
      measured at 8 weeks using a visual analogue scale (VAS) and Short Form 36 (SF
      36). RESULTS: VAS was significantly higher in early referral patients [mean (SD)
      58.4 (20) vs 50.4 (19), P=0.005], particularly if the first dialysis was planned
      [60.7 (20) vs 54.2 (20), P=0.03]. Planned patients also had higher SF-36 mental
      summary scores [45.4 (12) vs 39.7 (11), P=0.003], role emotional scores [58.0
      (43) vs 30.9 (38), P=0.003], and mental health scores [63.7 (24) vs 54.6 (22),
      P=0.01] than unplanned patients. Adjusting for centre and other confounding
      variables showed that having a planned first dialysis had an independent effect
      on QoL (VAS, and the SF-36's mental summary score, physical functioning, role
      physical, general health, role emotional and mental health). Early referral had
      no independent effect on QoL. Socio-economic status had an important positive
      effect on physical QoL. CONCLUSIONS: While the effect of early referral to a
      nephrologist on QoL appeared centre dependent, a smooth transition onto dialysis
      was associated with significantly better early QoL, independent of other
      variables.

PMID- 12808171
TI  - Risk factors for higher mortality at the highest levels of spKt/V in
      haemodialysis patients.
AB  - BACKGROUND: The survival of patients on haemodialysis improves as the delivered
      doses of dialysis attain a Kt/V of 1.2 or more. However, a consistent yet
      paradoxical finding in the Kt/V survival relationship is that the mortality tends
      to increase at the higher ends of Kt/V. METHOD: To determine the relationship of
      Kt/V with survival at a time when increasing doses of dialysis are being
      delivered and to examine the effect of body mass and nutritional markers
      including serum pre-albumin on the paradoxical relationship, we analysed relative
      mortality risk (RR) as a function of single-pool Kt/V (spKt/V) in the Cox
      proportional hazard model. We used body mass index (BMI), dry body weight and
      nutritional parameters including serum pre-albumin obtained in 1151 patients on
      chronic haemodialysis as covariates. RESULTS: The mean spKt/V for February and
      March of 1997 was 1.46+/-0.28 (+/-SD). A spKt/V of >1.2 was achieved in 82.5% of
      patients and 20% of patients received a spKt/V of >1.68. Using spKt/V in deciles
      and assigning the third decile (spKt/V 1.2-1.3) as the reference group with an RR
      of 1, the extreme first and the tenth deciles displayed a higher RR imparting a U
      shaped configuration to the curve. In this unadjusted analysis, there was no
      dependency between delivered dose of spKt/V and RR values. spKt/V values were re
      analysed in quintiles. The U-shaped relationship persisted between spKt/V and RR,
      and an unadjusted analysis again exhibited no clear dependency between spKt/V and
      RR. The patients in the highest fifth spKt/V quintile, who received the highest
      dose of dialysis and had the paradoxical increase in RR, had the lowest body
      weight, BMI, serum pre-albumin and creatinine. Adjustments for case-mix
      characteristics (age, gender, race and diabetes) in the Cox multivariate model
      did not reduce the paradoxical increase in RR. However, introduction of BMI or
      dry body weight along with serum creatinine and pre-albumin to the above case-mix
      covariates for the first time produced a dose-dependent inverse relationship
      between the first four quintiles of the spKt/V and their respective RR. With the
      above variables adjusted, the fifth quintile RR of 1.6 (0.9, 3.1) was reduced to
      0.9 (0.4, 2.0), but was not corrected to the lowest RR of 0.6 (0.2, 1.2) noted in
      the fifth spKt/V quintile. This difference between the adjusted RR of fifth and
      fourth quintile was not statistically significant, but persisted after adjusting
      for any clustering variation. CONCLUSIONS: Our analysis, which is the first to
      include serum pre-albumin in the Kt/V survival analysis, demonstrates a steeper
      rise in the unadjusted RR at the highest end of spKt/V levels than reported
      previously and suggests that patients with lower weight and nutritional
      parameters may mostly account for the spKt/V and RR paradox. As we find a
      worsening in the spKt/V-RR paradox at a time when higher doses of dialysis are
      being delivered, we speculate that factors other than underweight and
      malnutrition such as 'toxicity' of rapid dialysis, especially in sick and
      underweight patients, may contribute to the paradox. If future studies were to
      verify this possibility, sick and underweight patients could benefit from less
      vigorous but frequent sessions of haemodialysis.

PMID- 12808172
TI  - Symptom burden, quality of life, advance care planning and the potential value of
      palliative care in severely ill haemodialysis patients.
AB  - BACKGROUND: There has been little research on the potential value of palliative
      care for dialysis patients. In this pilot study, we sought (i) to identify
      symptom burden, health-related quality of life (HRQoL) and advance directives in
      extremely ill haemodialysis patients to determine their suitability for
      palliative care and (ii) to determine the acceptability of palliative care to
      patients and nephrologists. METHODS: Nineteen haemodialysis patients with
      modified Charlson co-morbidity scores of > or =8 were recruited. Each completed
      surveys to assess symptom burden, HRQoL and prior advance care planning.
      Palliative care specialists then visited patients twice and generated
      recommendations. Patients again completed the surveys, and dialysis charts were
      reviewed to assess nephrologists' (i) compliance with recommendations and (ii)
      documentation of symptoms reported by patients on the symptom assessment survey.
      Patients and nephrologists then completed surveys assessing their satisfaction
      with palliative care. RESULTS: Patients reported 10.5 symptoms, 40% of which were
      noted by nephrologists in patients' charts. HRQoL was significantly impaired.
      Thirty-two percent of patients had living wills. No differences were observed in
      symptoms, HRQoL or number of patients establishing advance directives as a result
      of the intervention. Sixty-eight percent of patients and 76% of nephrologists
      rated the intervention worthwhile. CONCLUSIONS: Extremely ill dialysis patients
      have marked symptom burden, considerably impaired HRQoL and frequently lack
      advance directives, making them appropriate candidates for palliative care.
      Patients and nephrologists perceive palliative care favourably despite its lack
      of effect in this study. A more sustained palliative care intervention with a
      larger sample size should be attempted to determine its effect on the care of
      this population.

PMID- 12808173
TI  - Characteristics of hypotension-prone haemodialysis patients: is there a critical
      relative blood volume?
AB  - BACKGROUND: Intradialytic morbid events (IME, mostly hypotension) mainly due to
      ultrafiltration-induced hypovolaemia still are the most frequent complication
      during haemodialysis (HD). This study was performed to test the hypothesis that
      there is an individual critical relative blood volume (RBV(crit)) in IME-prone HD
      patients. METHODS: In this prospective international multicentre study, 60 IME
      prone patients from nine dialysis centres were observed during up to 21 standard
      HD sessions without trial-specific intervention. The RBV was monitored
      continuously by an ultrasonic method (BVM; blood volume monitor). Also, the
      ultrafiltration rate was registered continuously. Blood pressure was measured at
      regular intervals, and more frequently during IME. All IME and specific
      therapeutic interventions were noted. RESULTS: In total, 537 IME, some with more
      than one symptom, were documented during 585 HD sessions. The occurrence of IME
      increased up to 10-fold from the start to the end of the HD session. RBV(crit)
      showed a wide inter-individual range, varying from 71 to 98%. However, the intra
      individual RBV limit was relatively stable, with an SD of <5% in three-quarters
      of the patients. In patients with congestive heart failure, cardiac arrhythmia,
      advanced age, low ultrafiltration volume and low diastolic blood pressure, higher
      values of RBV(crit) were observed. While all correlations between RBV(crit) and
      patient characteristics alone were found to be of weak or medium strength, the
      combination of diastolic blood pressure, ultrafiltration volume and age resulted
      in a strong correlation with RBV(crit): the linear equation with these parameters
      allows an estimation of RBV(crit) in patients not yet monitored with a BVM.
      CONCLUSIONS: An individual RBV limit exists for nearly all patients. In most IME
      prone patients, these RBV values were stable with only narrow variability, thus
      making it a useful indicator to mark the individual window of haemodynamic
      instabilities.

PMID- 12808174
TI  - TNF-alpha elimination with high cut-off haemofilters: a feasible clinical
      modality for septic patients?
AB  - BACKGROUND: Renal replacement therapies with high cut-off haemofilters are new
      approaches in the adjuvant therapy of sepsis. We analysed the cytokine
      elimination capacity of a newly developed polyflux high cut-off haemofilter.
      Different renal replacement therapies are compared and tested for their clinical
      feasibility. METHODS: Blood from healthy volunteers (n=15) was incubated for 4 h
      with 1 mg of endotoxin and then circulated through a closed extracorporeal
      circuit. A newly developed polyflux haemofilter (P2SX) was used. Haemofiltration,
      haemodialysis and albumin dialysis were tested. IL-1ra (17 kDa), interleukin-6
      (IL-6) (28 kDa), tumour necrosis factor alpha (TNF-alpha) (51 kDa), albumin (64
      kDa), creatinkinase (CK) (80 kDa) and IgG (140 kDa) were measured in blood and
      filtrates prior to the initiation and after 5 min, 1, 2 and 4 h. RESULTS:
      Haemofiltration was superior to haemodialysis in the clearance capacity of all
      substances when applied in the 1 l/h ultrafiltration mode. Increasing the
      ultrafiltration rate/dialysate flow from 1 to 3 l/h led to a significant increase
      in cytokine clearances (P<0.001). At 3 l/h the differences between
      haemofiltration and haemodialysis vanished and both techniques achieved
      comparable cytokine clearances. Median clearance values ranged between 25 and 54
      ml/min for interleukin-1 receptor antagonist (IL-1ra), 23 and 42 ml/min for IL-6
      and 15 and 28 ml/min for TNF-alpha. Albumin loss was highest in the
      haemofiltration group with albumin clearances ranging between 7 and 13 ml/min.
      Using diffusion instead of convection significantly reduced the loss of albumin
      (P<0.01 for 1 l/h, P<0.05 for 3 l/h). Albumin dialysis was able to completely
      inhibit albumin loss but cytokine clearance capacity was limited. CONCLUSIONS:
      High cut-off haemofilters achieve high clearances for inflammatory IL-6 and TNF
      alpha. Due to the high protein loss in haemofiltration, dialysis in combination
      with balanced protein substitution seems to be a suitable approach for clinical
      trials.

PMID- 12808175
TI  - Dialysis filter type determines the acute effect of haemodialysis on endothelial
      function and oxidative stress.
AB  - BACKGROUND: Endothelial function of large arteries is impaired in chronic
      haemodialysis patients and oxidative stress due to the dialysis procedure has
      been suggested as a causal factor. However, it is not clear whether different
      types of dialysis membranes affect endothelial function differently. Therefore we
      determined endothelium-dependent, flow-mediated dilatation (FMD) of the brachial
      artery as well as markers of oxidative stress immediately before and after
      haemodialysis (HD) with either a cellulosic cuprophane or a synthetic
      polysulphone dialyser in a blinded, randomized, cross-over study. METHODS: Twelve
      haemodialysis patients (age 55+/-3 years, time on dialysis 20+/-2 months, mean
      fluid change -1782+/-21 ml, systolic/diastolic blood pressure 139/75 mmHg) were
      included. Using a multi-gate-pulsed Doppler system (echo-tracking device)
      brachial artery FMD and nitroglycerine-induced, endothelium-independent
      vasodilatation (NMD) were measured. Patients were randomized to HD with either a
      polysulphone or a cuprophane membrane and were crossed over to the other filter.
      Investigators were blinded to the type of membrane used. Serum concentrations of
      oxidized LDL (oxLDL) and alpha-tocopherol as markers of oxidative stress were
      measured before and after each dialysis session. RESULTS: Data are given as
      mean+/-SEM. Treatment with polysulphone filter HD did not significantly affect
      FMD (baseline 9.3+/-2.0% vs after HD 9.6+/-1.8%). After dialysis with a
      cuprophane membrane FMD decreased from 9.4+/-2.1 to 7.4+/-1.8% (P<0.05). NMD was
      not significantly affected by HD irrespective of the membrane material used.
      Serum levels of oxLDL were not changed by either treatment; however, alpha
      tocopherol concentrations fell significantly after dialysis with the cuprophane
      filter (baseline 18.0+/-2.3 after HD 16.6+/-1.3 micro g/ml, P<0.05), while alpha
      tocopherol levels remained unchanged when the polysulphone membrane was used.
      CONCLUSIONS: The type of dialysis filter membrane determines the acute effect of
      haemodialysis on arterial endothelial function. Differences in biocompatibility
      and oxidative stress may account for the observed differential effects, since the
      decrease of FMD after dialysis with a cellulosic cuprophane membrane-but not with
      a synthetic polysulphone membrane-was associated with a reduction in serum
      vitamin E.

PMID- 12808176
TI  - Different effects of enoxaparin and unfractionated heparin on extrinsic blood
      coagulation during haemodialysis: a prospective study.
AB  - BACKGROUND: Heparin inhibits prothrombotic tissue factor (TF) and releases its
      inhibitor, tissue factor pathway inhibitor (TFPI), from the endothelium, but
      repeated administration of heparin depletes vascular stores of TFPI. We studied
      the anticoagulant effects of unfractionated heparin (UFH) vs low-molecular-weight
      enoxaparin-used for thrice-weekly maintenance haemodialysis (HD)-on plasma levels
      of total TF and TFPI and on those of an activated coagulation marker prothrombin
      fragment 1+2 (PF 1+2). METHODS: Twenty-five patients dialysed using a single
      injection of enoxaparin (at a mean dose of 0.68 mg/kg) were randomly assigned to
      either receive UFH administered as a mean bolus of 42.1 IU/kg and continuous
      infusion of 57.8 IU/kg (n=12) or to be maintained on enoxaparin (n=13), and were
      followed prospectively for 12 weeks. Plasma immunoreactive TF, TFPI and PF 1+2
      were measured at the start and after 10 and 180 min of HD, and compared with
      values in 15 healthy controls. RESULTS: Pre-dialysis TF, TFPI and PF 1+2 were
      higher than normal (all P<0.0001). TF and PF 1+2 did not change, while TFPI
      levels, compared with baseline, increased at each interval in enoxaparin
      anticoagulated HD patients (all P<0.0001). TFPI increments correlated inversely
      with pre-dialysis TFPI (both P<0.0007). In patients switched to UFH, TF levels
      remained unchanged compared with pre-randomization values, TFPI increased at each
      interval of HD sessions (all P<0.035) and PF 1+2 increased pre-dialysis
      (P=0.015). The over-dialysis effects of UFH resembled those of enoxaparin. In
      contrast, baseline TFPI and its 10-min rise correlated inversely with the UFH
      loading dose (both P<0.040). Pre-dialysis PF 1+2 was inversely associated with
      TFPI increments (both P<0.034), and directly with pre-dialysis TFPI (P=0.018) and
      the UFH loading dose (P=0.045). CONCLUSIONS: Depletion of heparin-releasable
      stores of TFPI is an untoward effect of repeated anticoagulation during
      maintenance HD therapy. The traditional UFH regimen is more prothrombotic than
      single enoxaparin injections, with high loading doses of UFH being involved in
      TFPI exhaustion and subsequent hypercoagulability.

PMID- 12808177
TI  - Nutritional effects of increasing dialysis dose by adding an icodextrin daytime
      dwell to Nocturnal Intermittent Peritoneal Dialysis (NIPD) in children.
AB  - BACKGROUND: To assess the need to adapt dietary prescriptions, we studied
      potential effects of increasing the dialysis dose by adding a daytime icodextrin
      dwell, in children on Nocturnal Intermittent Peritoneal Dialysis (NIPD), on
      peritoneal amino acids (AA) and albumin loss, AA, albumin, cholesterol and
      fibrinogen plasma levels and nutritional intake. METHODS: A cross-over study in
      eight children (age 2-12 years) on NIPD at baseline (week 1). INTERVENTION: to
      increase dialysis dose we added a daytime dwell with 1100 ml/m(2) icodextrin
      solution for a week (week 2). MAIN OUTCOME MEASURES: peritoneal albumin loss
      (quantified by nephelometry) and AA loss (quantified by liquid chromatography
      mass spectrometry) in the last 72 h dialysate collections of weeks 1 and 2. On
      days 7 and 14, morning blood sample was taken for urea, creatinine, plasma AA
      levels, serum albumin, cholesterol and fibrinogen determination. Nutritional
      intake diaries were kept throughout the study period. RESULTS: Weekly dialysis
      creatinine clearance increased from 35 to 65 l/1.73 m(2) (P<0.0001) and Kt/V from
      1.99 to 2.54 (P<0.01). Peritoneal albumin loss did not change significantly
      (2.4+/-0.4 to 2.4+/-0.3 g/m(2)/24 h) nor did serum albumin (3.25+/-0.52 to 3.21+/
      0.25 g/dl), cholesterol (216+/-73 to 240+/-61 mg/dl) and fibrinogen (385+/-40 to
      436+/-64 mg/dl). There was a significant increase in loss of essential (EAA)
      [1122+/-200 to 2104+/-417 mg/m(2)/week (P<0.0001)] and non-essential amino acids
      (NEAA) [6160+/-1341 to 10406+/-2899 mg/m(2)/week (P<0.001)]. Plasma AA levels did
      not change significantly except for a drop in histidine and glutamine. Dietary
      protein intake did not change from 43+/-12 to 41+/-8 g/m(2)/day, caloric intake
      from 73+/-21 to 70+/-24 kcal/kg/day. CONCLUSIONS: Increasing dialysis dose by
      introducing a daytime icodextrin dwell during a week does not affect peritoneal
      albumin loss, serum albumin, cholesterol and fibrinogen levels nor dietary intake
      on a short term. There is a significant increase in EAA and NEAA loss without
      change in plasma levels. We suggest monitoring dietary intake when adding a
      daytime icodextrin dwell in children.

PMID- 12808178
TI  - Tranexamic acid is beneficial as adjunctive therapy in treating major upper
      gastrointestinal bleeding in dialysis patients.
AB  - BACKGROUND: In a pilot, non-randomized trial we tested the efficacy of tranexamic
      acid (TXA), a potent fibrinolytic inhibitor, as adjunctive therapy in standard
      treatment of major upper gastrointestinal bleeding in dialysis patients. METHODS:
      Twenty consecutive patients (12 male, eight female; 63+/-8 years) with 36
      episodes of major upper gastrointestinal bleeding were included in the study. In
      16 episodes of bleeding TXA was used (in a dosage of 20 mg intravenously,
      followed for the next 4 weeks by 10 mg/kg/48 h orally), whereas in 20 other cases
      of bleeding, TXA was not used. The decision to use TXA was left to the attending
      physician's clinical judgement, resulting in all the more severe cases of
      bleeding being treated with TXA. RESULTS: Treatment including TXA was shown to be
      beneficial (relative to cases not treated with TXA) in terms of decreasing the
      rate of early re-bleeding (in the first week, 0 vs 6, P<0.05), the rate of early
      and late re-bleeding (in the first month, 1 vs 8, P<0.05), the rate of repeated
      endoscopic procedures (in the first month, 1 vs 8, P<0.05) and the number of
      blood transfusions needed (in the first month, 1.4+/-1.3 vs 2.6+/-1.5 units,
      P<0.05). CONCLUSIONS: The results of this pilot study suggest that TXA can be
      beneficial in the treatment of major upper gastrointestinal bleeding in dialysis
      patients. This remains to be definitely confirmed in a randomized study.

PMID- 12808179
TI  - Over-expression of platelet-derived growth factor in human diabetic nephropathy.
AB  - BACKGROUND: The pathogenetic mechanisms responsible for progressive renal
      impairment of diabetic nephropathy are still poorly understood, despite its
      growing incidence. Increasing evidence suggests that growth factors may
      contribute to the initiation and progressive fibrosis of diabetic nephropathy. In
      this study, the gene expression and protein distribution of platelet-derived
      growth factor-A and -B (PDGF-A and PDGF-B) in human diabetic nephropathy were
      examined. METHODS: PDGF-A and PDGF-B mRNA levels in surplus renal biopsy tissue
      from seven patients with overt diabetic nephropathy and six nephrectomy samples
      were examined using quantitative reverse transcription-polymerase chain reaction
      (RT-PCR). In addition, each sample was also examined immunohistochemically to
      quantify and localize peptide expression of each PDGF isoform. RESULTS: Gene
      expression of PDGF-A and PDGF-B mRNA were increased 22- and 6-fold, respectively,
      in biopsies from patients with diabetic nephropathy compared with control tissue.
      Immunostaining also demonstrated increased peptide expression of both PDGF-A and
      PDGF-B in diabetic nephropathy, with each isoform showing a specific pattern of
      tissue distribution. CONCLUSIONS: The findings of increased gene and protein
      expression of PDGF in renal biopsies from patients with diabetic nephropathy
      imply a potential role for this prosclerotic growth factor in the development of
      the progressive fibrosis that characterizes human diabetic kidney disease.

PMID- 12808180
TI  - Clinical and Doppler ultrasonography data of a polyurethane vascular access graft
      for haemodialysis: a prospective study.
AB  - BACKGROUND: Absence of a permanent vascular access in most patients starting
      haemodialysis remains a cause of high morbidity and costs. This study obtained
      new clinical and colour Doppler ultrasound (CDU) data of a polyurethane vascular
      access graft (PVAG) proposing early post-operative cannulation. METHODS: Baseline
      characteristics were determined in 15 patients and the PVAGs were evaluated
      prospectively including first cannulation, patency and complications. CDU was
      used post-operatively and after 1 year for assessing graft morphology and access
      blood flow. RESULTS: PVAGs were cannulated at a median of 4 days post
      operatively. The 1-year primary patency of the PVAG was 66.7%. During the 15
      months observation three grafts thrombosed, one was replaced because of infection
      and one because of ischaemia. CDU measurements at the feeding brachial artery
      revealed a mean initial access volume flow of 773+/-89 ml/min, being
      significantly higher in patients without thrombosis compared to patients with
      thrombotic events (930+/-90 vs 375+/-143 ml/min, P<0.05). The initial inability
      to directly monitor PVAGs by CDU changed at sites of frequent centesis, where
      Doppler signals and luminal morphology could be evaluated in the follow up
      examination. CONCLUSIONS: The PVAG offers early access for urgent haemodialysis.
      CDU for access volume flow measurement at the feeding brachial artery contributes
      to predict access thrombosis. Direct non-invasive graft imaging is limited and
      the ultrasonographical changes in the polyurethane material enabling graft
      monitoring after repeated cannulation might indicate an injury of the graft with
      increased risk for access failure.

PMID- 12808181
TI  - Two kidney-transplant women with therapy-resistant hypertension: diagnostic error
      of a renal artery stenosis.

PMID- 12808182
TI  - Dialysis-resistant pulmonary oedema.

PMID- 12808183
TI  - Permanent catheter implantation via a persistent left superior vena cava.

PMID- 12808185
TI  - Challenges in taking care of patients on chronic haemodialysis.

PMID- 12808186
TI  - Liquid test and sudden death in dialysis patients.

PMID- 12808189
TI  - Haemodialysis increases QTc interval but not QTc dispersion in ESRD patients
      without manifest cardiac disease.

PMID- 12808191
TI  - Once weekly administration of erythropoietin.

PMID- 12808193
TI  - Does fasciotomy hurt the patients with crush syndrome?

PMID- 12808194
TI  - Frequent prolonged home haemodialysis.

PMID- 12808197
TI  - Platelet-derived growth factor-producing cells immortalized from rat
      mesencephalon with SV40 large T antigen transduced by an AAV vector.
AB  - PURPOSE: Adeno-associated virus (AAV) can infect a wide variety of mammalian cell
      types and is capable of infecting both dividing and non-dividing cell
      populations. Here we report the construction of a recombinant AAV vector which
      expresses the SV40 large T protein (AAV-T) and the use of this vector to
      immortalize primary cells from embryonic rat mesencephalon. METHODS: The AAV-T
      vector was constructed by introducing the BamH1 fragment of the pCMV/SVE/Neo
      plasmid containing T antigen and SV40 regulatory elements into the JM48 plasmid
      containing the inverted terminal repeats of AAV. Neuronal cultures from E-12 rat
      mesencephalon were grown in defined media supplemented with basic fibroblast
      growth factor. These cells were infected with the AAV-T vector. RESULTS: A cell
      line (designated RMAT) and six subclones were established from these cultures
      through multiple passages. This cell line was immunoreactive for SV40 large T
      antigen and the cytoskeletal proteins nestin and vimentin. Morphological
      differentiation and expression of neurofilament 160 kDa were induced by exposure
      to dibutyrl cyclic AMP. Immunoassays performed to measure endogenous production
      of growth factors showed that RMAT cells produced high levels of platelet-derived
      growth factor (PDGF). CONCLUSIONS: AAV may be a useful vector for the
      transduction of oncogenes to produce cell lines.

PMID- 12808198
TI  - Regeneration of ganglion cell axons into a peripheral nerve graft alters retinal
      expression of glial markers and decreases vulnerability to re-axotomy.
AB  - PURPOSE: To compare the effect of cutting the optic nerve versus replacing the
      cut optic nerve with a peripheral nerve (PN) graft on retinal glial markers, and
      to determine whether the PN graft can stabilize regenerating retinal ganglion
      cells (RGCs), thus preventing their death following re-axotomy. METHODS: Retinas
      harvested after ganglion cell regeneration into a sciatic nerve graft were
      compared to untreated control retinas and retinas obtained following optic nerve
      axotomy. Glial-specific proteins such as glial fibrillary acidic protein (GFAP),
      Bcl-2 and complement-3 receptor (Ox-42) were examined using immunohistochemistry.
      Ganglion cells that survived the second axotomy were quantified on retinal flat
      mounts by retrograde labeling from the graft. RESULTS: GFAP expression in
      astrocytes and Muller cells was elevated in axotomized retinas when compared to
      controls, and an additional up-regulation in Muller cells was found in retinas
      following ganglion cell regeneration. Increased GFAP expression in retinas
      containing regenerated neurons was accompanied by increased Bcl-2 expression with
      latter being confined to Muller cells. Moreover, re-axotomy of the regenerated
      axons within the graft did not result in significant retrograde degeneration of
      RGCs within 28 days. CONCLUSIONS: The data suggest that the graft stabilizes the
      regenerating RGCs to an extent reminiscent of peripheral neurons, a process that
      may involve the interaction between neuronal and glial elements.

PMID- 12808199
TI  - Rehabilitation of chronic post-stroke visual field defect with computer-assisted
      training: a clinical and neurophysiological study.
AB  - PURPOSE: Our aim was to study whether homonymous visual field defects could be
      restored in chronic stroke patients (N = 5) using computer-assisted training, and
      whether the possible beneficial effect could be maintained. Visual evoked
      potential (VEP) recordings were applied to evaluate whether they could
      demonstrate the possible training effects at the cortical level. METHODS: We
      applied a specially designed computer program in the training. Subjective
      assessment, static and kinetic perimetry, and pattern reversal hemifield VEP
      recordings were used to detect the possible changes. RESULTS: Two patients showed
      improvements immediately after the training in static perimetry. Further
      improvements were detected at a later follow-up in three patients. With kinetic
      perimetry, improvements were detected in three patients. The visual field defect
      was detected with VEP recordings in four patients before the training, and
      improvements could be verified with the method in three patients, two of which
      clearly improved in the static perimetry as well. CONCLUSIONS: In three patients,
      the visual defect diminished with the computer-assisted method. It seems evident
      that visual field defects resulting from stroke can be partially restored even in
      the chronic phase.

PMID- 12808200
TI  - CGP 3466 increases survival of cultured fetal dopaminergic neurons.
AB  - PURPOSE: To analyze the effects of CGP 3466, a compound structurally related to
      deprenyl, on survival and function of fetal ventral mesencephalic dopaminergic
      neurons. METHODS: Free-floating roller tube (FFRT) cultures of rat (E14) ventral
      mesencephalon were treated with CGP 3466 [10-8 M] for 7 days. Tyrosine
      hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunocytochemistry
      was performed to allow analysis of dopaminergic neurons and astroglial cells,
      respectively. Lactate dehydrogenase activity in the culture medium served as a
      measure of cell death. Control and CGP 3466 treated cultures were grafted into 6
      hydroxydopamine-lesioned rats, and graft survival and function evaluated 9 weeks
      posttransplantation. RESULTS: FFRT cultures treated with CGP 3466 contained
      significantly more (two fold) surviving TH-immunoreactive (-ir) neurons and
      decreased lactate dehydrogenase activity in the culture medium compared to
      controls. The actions of CGP 3466 seem not to be mediated by astroglial cells,
      since GFAP-ir cell numbers and GFAP protein levels did not differ between the
      groups. CGP 3466 pretreatment of donor cultures did not improve TH-ir cell
      survival in the grafts nor did it alter functional recovery as compared to
      controls. CONCLUSIONS: CGP 3466 is an effective survival factor for cultured
      midbrain dopaminergic neurons. However, CGP 3466 pretreatment does not ameliorate
      survival and function of the dopaminergic neurons after grafting into a rat model
      of Parkinson's disease.

PMID- 12808201
TI  - Spontaneous recovery of locomotion induced by remaining fibers after spinal cord
      transection in adult rats.
AB  - PURPOSE: A major issue in analysis of experimental results after spinal cord
      injury is spontaneous functional recovery induced by remaining nerve fibers. The
      authors investigated the relationship between the degree of locomotor recovery
      and the percentage and location of the fibers that spared spinal cord
      transection. METHODS: The spinal cords of 12 adult rats were transected at T9
      with a razor blade, which often resulted in sparing of nerve fibers in the
      ventral spinal cord. The incompletely-transected animals were used to study the
      degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB
      rating scale, in correlation to the extent and location of the remaining fibers.
      RESULTS: Incomplete transection was found in the ventral spinal cord in 42% of
      the animals. The degree of locomotor recovery was highly correlated with the
      percentage of the remaining fibers in the ventral and ventrolateral funiculi. In
      one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus
      were able to sustain a certain recovery of locomotion. CONCLUSIONS: Less than 5%
      of remaining ventrolateral white matter is sufficient for an unequivocal motor
      recovery after incomplete spinal cord injury. Therefore, for studies with spinal
      cord transection, the completeness of sectioning should be carefully checked
      before any conclusion can be reached. The fact that the degree of locomotor
      recovery is correlated with the percentage of remaining fibers in the
      ventrolateral spinal cord, exclusive of most of the descending motor tracts, may
      imply an essential role of propriospinal connections in the initiation of
      spontaneous locomotor recovery.

PMID- 12808202
TI  - Changes in protein levels of elongation factors, eEF1A-1 and eEF1A-2/S1, in long
      term denervated rat muscle.
AB  - PURPOSE: This study was designed to determine whether the quantitative
      relationship between the levels of the eEF1A-1(developmental) and eEF1A-2/S1
      (adult) isoforms of peptide elongation factor remains stable after denervation of
      skeletal muscle or whether in response to denervation the relative amount of the
      developmental form would increase. In normal postnatal rat muscle, eEF1A-2/S1 is
      the dominant form represented, and levels of eEF1A-1 are extremely low. METHODS:
      One hind limb in young adult rats was permanently denervated. Denervated and
      corresponding contralateral control muscles were removed for biochemical and
      morphological analysis from 2 days to 25 months after denervation. RESULTS: By
      one month after denervation, relative levels of eEF1A-1 rose dramatically in
      relation to those of eEF1A-2/S1, and they remained high throughout the remainder
      of the 25-month denervation period. Ultrastructural analysis showed a complex mix
      of muscle fiber atrophy, dying muscle nuclei and muscle fibers, and newly forming
      muscle fibers in the same tissue. CONCLUSIONS: As during muscle regeneration,
      levels of the developmental eEF1A-1 isoform of peptide elongation factor greatly
      increased relative to those of the adult eEF1A-2/S1 adult isoform following
      denervation in rat muscles. However, in contrast to regeneration, the elevated
      level of eEF1A-1 did not return to the basal minimal level. Since switching from
      eEF1A-1 to eEF1A-2/S1 is an indicator that terminal differentiated is completed,
      the failure of eEF1A-1 to return to basal level may be indicative of the
      persistence of an unstable tissue environment that includes muscle fiber atrophy,
      degeneration and neomyogenesis. The specific cellular basis for the increase in
      eEF1A-1 could not be determined from this study.

PMID- 12808203
TI  - Activation of A(3) receptors by endogenous adenosine inhibits synaptic
      transmission during hypoxia in rat cortical neurons.
AB  - PURPOSE: The aim of our study was to characterize the influence of A(3) receptors
      on synaptic potentials (PSPs) in pyramidal cells from the rat cingulate cortex
      during hypoxia. METHODS: Intracellular recordings (n=49) were taken from slice
      preparations. PSPs were evoked by electrical stimulation. RESULTS: Hypoxia
      (95%N(2)-5%CO(2), 5 min) reduced the amplitude of the PSPs significantly. The
      effect was more pronounced in the presence of adenosine re-uptake inhibitor S-(p
      nitrobenzyl)-6-thioguanosine (NBTG) and deaminase inhibitor erythro-9-(2-hydroxy
      3-nonyl)adenine (EHNA); the effect was completely reversed by bovine adenosine
      deaminase. Hypoxic inhibition induced after A(1) receptor blockade with 1,3
      dipropyl-8-cyclopentylxanthine (DPCPX) in the presence of NBTG was completely
      reversed by the A(3) antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino]
      1,2,4-triazolo[1,5-c]quinazoline (MRS 1220), indicating the involvement of A(3)
      receptors in hypoxic PSP inhibition. This was confirmed by A(3) agonist N(6)-(3
      iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) inhibiting PSPs. The
      effect of IB-MECA was blocked by the rat A(3) receptor-selective antagonist 3
      propyl-6-ethyl-5-[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate
      (MRS 1523) and was not observed in the presence of G-protein inhibitor guanosine
      5'-O-2-thiodiphosphate (GDP-beta-S). CONCLUSION: We conclude that a high level of
      endogenous adenosine, which occurs during hypoxia, activates A(3) receptors.
      Their activation contributes to PSP inhibition by adenosine during hypoxia.

PMID- 12808204
TI  - Xenotransplantation of porcine pancreatic endocrine cells to total
      pancreatectomized dogs.
AB  - Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion
      chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total
      pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups
      of 3 dogs each. In three dogs of the control group, exogenous insulin was
      administered twice a day for 30 weeks to maintain fasting blood glucose (FBG)
      levels within the normal range. The remaining three dogs were implanted with Bio
      AEPs (implantation group), in addition to daily insulin administration. In the
      implantation group, Bio-AEPs containing 1.3 to 1.8 x 10(7) cells per kg of body
      weight of the recipient were implanted without fixation into the abdominal
      cavity. In the control group, exogenous insulin requirements did not decrease
      during the experimental period, whereas it significantly decreased for a certain
      period (3, 11, 17 weeks) after implantation in all implanted dogs. In the
      implantation group, laparotomy was performed after FBG and the exogenous insulin
      requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were
      completely destroyed, and the remaining one was encapsulated by thin fibrous
      tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was
      not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia,
      of the PE-cells was observed on transmission electron microscopy. In conclusion,
      Bio-AEP could function for a certain period after implantation in this study.
      However, more preclinical researches should be needed to apply this technique for
      the treatment of diabetic dogs.

PMID- 12808205
TI  - An automated experimental milker for rat.
AB  - The development of sucking pressure was investigated with an artificial nipple in
      16 male and female rat pups on postnatal days 4, 7, 10, 14, and 18. The rat pups
      refused to suck on the artificial nipple on postnatal day 14 or day 18 thus
      negative sucking pressure had to be calculated by regression analysis. As a
      result, the mean maximum intra-oral negative sucking pressure on day 18 was
      calculated to be -160.1 mmHg in the male and -103.4 mmHg in the female. Based on
      these results, the maximum level of negative pressure of the automated
      experimental rat milker was set at -160 mmHg. The automated experimental milker
      for rat is able to collect milk from lactating mothers by alternating negative
      and atmospheric pressures through two solenoid valves and a vacuum pump attached
      to a microcomputer. Mother rats were milked with the automated experimental
      milker on postpartum days 4, 7, 10, 14 and 18 of a single lactation period. The
      maximum mean milk yield with this machine was 3.18 +/- 1.37 g, obtained on day 14
      of the lactation period. This quantity is considerably lower than previously
      reported values obtained by measuring differences in body weight of the offspring
      and mother rat before and after suckling. It is necessary to further optimize
      this system, but the milk yield in the present study is adequate for chemical
      analysis.

PMID- 12808206
TI  - Pre-exposure treatment of cats with anti-FHV-1 and anti-FCV mouse-cat chimeric
      antibodies.
AB  - Prior to pre-exposure treatment of cats with two mouse-cat chimeric antibodies,
      FJH2 and F1D7, having neutralizing activity to feline herpesvirus-1 (FHV-1) and
      cat calicivirus (FCV), respectively, these chimeric antibodies were labeled with
      (125)I and administered to cats to examine their blood kinetics. Concentrations
      of the both administered chimeric antibodies in the blood reached maximum at the
      48th hour post-administration, and the level was 34% for FJH2 and 54% for F1D7.
      Then the concentration levels declined gently, and decreased afterwards to 8.2%
      for FJH2 and 25% for F1D7 on the 20th day post-administration. The blood half
      lives of FJH2 and F1D7 were 8.3 days and 10.7 days, respectively. In order to
      examine effectiveness in pre-exposure treatment of cats with these chimeric
      antibodies, cats were administered on the 15th day prior to the challenge
      infections with FHV-1 and FCV by subcutaneous route with 0.5 ml/kg of an FJH-F1D7
      mixture being adjusted to contain each chimeric antibody of 10 mg/ml. The cats
      that received the pre-exposure treatment with the cocktail, showed obvious
      reductions in manifestations of symptoms caused by those viral infections. The
      protective effectiveness of the pre-exposure treatment against these viral
      challenge infections was almost equal to that of the treatment given at right
      after these challenge infections.

PMID- 12808207
TI  - Persorption of bovine lactoferrin from the intestinal lumen into the systemic
      circulation via the portal vein and the mesenteric lymphatics in growing pigs.
AB  - The absorption and the transportation of intestinally administrated bovine
      lactoferrin (LF) were immunohistochemically and physiochemically investigated in
      the small intestine of growing pigs. At the apical halves of the small intestinal
      villi, bovine LF was absorbed by transcytosis as small vesicles through villous
      columnar epithelial cells. The presence of bovine LF-positive membranes of
      transcytotic vesicles suggests that the absorption was mediated by LF-binding
      factors on the epithelial cell membranes. Almost all of the absorbed bovine LF
      was demonstrated to be transported via the lymphatics and the portal vein into
      the systemic circulation. The LF-concentration in systemic circulation was
      significantly higher at 1 hr following intestinal administration of bovine LF.
      Bovine LF-positive lymphocytes also were transferred into the systemic
      circulation from intestine via the lymphatics and the portal vein.

PMID- 12808208
TI  - Molecular cloning of the feline telomerase reverse transcriptase (TERT) gene and
      its expression in cell lines and normal tissues.
AB  - Telomerase is a kind of reverse transcriptase which synthesizes and elongates
      telomeres. Telomerase activity is detected in many naturally occurring tumors and
      its expression appears to play an important role in the immortalization of tumor
      cells. In this study, cDNA encoding the feline telomerase reverse transcriptase
      (TERT) gene was cloned partially from a feline lymphoma cell line. The clone
      obtained in this study was 237 bp long including a reverse transcriptase motif 2,
      and was shown to have amino acid sequence similarity of 81.0% and 58.2% with
      human and mouse TERT cDNAs, respectively. TERT mRNA expression was detected in
      telomerase-positive cells (FL74, FT-1, 3201, FKNp, FONp, and FYMp), and was not
      detected in telomerase-negative cells (normal fibroblasts and CRFK). TERT mRNA
      was detected in various normal tissues including the spleen, pancreas, stomach,
      cerebrum, testis, bone marrow, lymph node and thymus, and relatively high-level
      expression was observed in the small bowel and large bowel. No expression of TERT
      mRNA was detected in the liver, adrenal gland, urinary bladder and lung. The TERT
      cDNA clone and the results obtained in this study will be useful for further
      investigation of feline tumors.

PMID- 12808209
TI  - Lymphocyte subsets and specific IgG antibody levels in clindamycin-treated and
      untreated dogs experimentally infected with Babesia gibsoni.
AB  - This study was carried out to clarify the role of lymphocyte subpopulations and
      Babesia-specific antibody on the treatment of clindamycin in dogs infected with
      B. gibsoni. Ten beagle dogs were divided into two groups: an untreated group (5
      dogs) and a clindamycin-treated group (5 dogs), which was administered
      clindamycin at 25 mg/ kg body weight, per os, q 12 hr from 7 days to 21 days post
      infection (PI). On the acute stage of infection, clindamycin treatment resolved
      anaemia and other clinical findings. There were no significant differences
      between treated and untreated dogs either in parasitemia levels or Babesial IgG
      antibody levels. However, morphological changes that indicated degeneration in
      the majority of parasites were observed. The numbers of CD4(+) showed a
      significant increase in treated dogs, especially after treatment. On the chronic
      stage, CD4(+) cells maintained high level both of the treated and untreated dogs.
      Although parasitemia maintained low level, their relapses were occurred on the
      49th day PI in treated dogs and on the 42nd and 63rd PI in untreated dogs. A
      rapid humoral antibody response was observed in treated dogs, however, lower
      humoral antibody responses in untreated dogs after relapses. The antibody levels
      of treated dogs were significantly higher than those of untreated dogs. These
      results suggested that clindamycin might not eliminate rapidly parasites from
      peripheral blood, but damage parasites, which might stimulate efficiently humoral
      and cellular immunity against Babesia infection, and result in an improvement of
      clinical conditions.

PMID- 12808210
TI  - Viability and infectivity of Cryptosporidium parvum oocysts detected in river
      water in Hokkaido, Japan.
AB  - The viability and infectivity of Cryptosporidium parvum (C. parvum) oocysts,
      detected in water samples collected from river water in Hokkaido, were
      investigated using Severe Combined Immunodeficient (SCID) mice. The water samples
      collected from September 27 through October 10, 2001 by filtration using Cuno
      cartridge filters were purified and concentrated by the discontinuous centrifugal
      flotation method. From 1.2 x 10 (5) liters of the raw river water, approximately
      2 x 10(4) oocysts were obtained and designated as Hokkaido river water 1 isolate
      (HRW-1). Oocyst identification was carried out using microscopic and
      immunological methods. Six 8-week-old female SCID mice were each inoculated
      orally with 1 x 10 (3) oocysts. Infection was successfully induced, resulting in
      fecal oocyst shedding. Oocysts were then maintained by sub-inoculation into SCID
      mice every 3 months. Infectivity was evaluated by making comparisons with two
      known C. parvum stocks, HNJ-1 and TK-1, which were bovine genotypes detected in
      fecal samples from a cryptosporidiosis patient and young cattle raised in
      Tokachi, Hokkaido respectively. The oocyst genotypes were determined from a small
      subunit ribosomal RNA (SSU-rRNA) gene by polymerase chain reaction - restriction
      fragment length polymorphism (PCR-RFLP) analysis. No significant differences were
      observed in the average number of oocysts per gram of feces (OPG) in any of the
      isolates. Our data indicates that the C. parvum oocysts detected in the sampled
      river water were of C. parvum genotype 2. Moreover, our data on the continued
      isolation, detection and identification of the C. parvum isolates is consistent
      with the available epidemiological data for the Tokachi area.

PMID- 12808211
TI  - A comparison of the phenotype of dendritic cells derived from discrete Peyer's
      patch macrophages of non-infected and Toxoplasma gondii infected mice.
AB  - A comparison of the expression of surface membrane antigens between dendritic
      cells (DC) derived from Peyer's patch macrophages (DPP-DC) of non-infected and
      Toxoplasma gondii (T. gondii) infected mice was performed. C57BL/6J mice aged 6-8
      weeks of both sexes were infected orally with a 0.5 ml suspension containing 2 x
      10(4) bradyzoites of the Beverley strain of T. gondii, sacrificed on day 8 and DC
      generated using discrete Peyer's patch macrophages (DPP-Mo) as progenitor cells.
      When a comparison of the expression of surface membrane antigens between the
      antigen presenting cells (APC) obtained from discrete Peyer's patches of non
      infected and T. gondii infected mice was carried out, no significant differences
      were observed in the macrophage progenitor and DC populations expression of
      F4/80, DEC-205, CD11c, CD80 (B7-1) and CD34. However, a significant decrease in
      MHC class II antigen levels and a down regulation of the co-stimulatory molecule
      CD86 (B7-2) were noted. B7-1 appeared to be the dominant co-stimulatory ligand,
      whereas B7-2, which was down regulated during T. gondii infection, had a weak
      expression. Taken together, these results may help clarify the role of DC in the
      complex network regulating surface membrane antigens, as well as, their capacity
      for antigen uptake, processing and presentation during toxoplasmosis.

PMID- 12808212
TI  - Relation between phenotype of tumor cells and clinicopathology in bovine
      leukosis.
AB  - Thirty-three cases of enzootic bovine leukosis (EBL) and 14 cases of sporadic
      bovine leukosis (SBL) were examined by immunohistochemistry using 6 monoclonal
      antibodies against leukocyte differentiation molecules of bovine leukocytes.
      There were 17 cases of B-1a cell type, 10 cases of B-1b cell type and 6 cases of
      B-2 cell type in EBL, and 5 cases originating from B cells (B-2 cell type) and 9
      cases originating from immature T cells in SBL. The average age for the EBL cases
      of B-1a cell type was 8.6 years, B-1b cell type was 6.5 years, and of B-2 cell
      type was 4.5 years. In cases of SBL, immature T cell type patients were younger
      than B-2 cell type ones. The lymphoma originating from B cells differed from that
      originating from T cells in morphology. In T cell tumors, the nucleus of tumor
      cells was round, the edge of the cytoplasm obvious, and tumor cells were
      sporadically present and proliferated. When compared with T cells, the region
      among B cells was obscure. But, there was no relation between phenotype and the
      histologic classification of tumor cells. In EBL, beyond the lymph node, tumors
      of B-1a and B-1b types had developed in the heart and abomasum, and those of the
      B-2 type tended to occur in liver. In SBL, B-2 type and T type cells formed
      tumors in the liver, kidney, thymus, and one case of T-cell type tumor formed on
      the skin. We would like to propose a new classification of bovine leukosis as
      EBL, calf type B-cell lymphoma, juvenile T-cell lymphoma and skin type T-cell
      lymphoma.

PMID- 12808213
TI  - Development of Peyer's patch and cecal tonsil in gut-associated lymphoid tissues
      in the chicken embryo.
AB  - It is well known that chicken B cells develop in the bursa of Fabricius (BF),
      which is categorized as gut-associated lymphoid tissue (GALT). Chicken GALT also
      includes Peyer's patch (PP) and cecal tonsil (CT). The relationship between these
      tissues in GALT during B cell development is currently unknown. In this study, we
      conducted comparative examination of PP, CT and BF development during
      embryogenesis using immunohistochemical staining. On day 13 of embryogenesis
      (E13), accumulation of MHC class II(+) cells was observed in the intestine.
      Thereafter, Bu-1(+) cells and IgM(+) cells appeared, and their number
      continuously increased at the same sites where MHC class II(+) cells were
      present. Similar results were obtained in the CT. The locations of embryonic PP
      were limited to two sites; near the Meckel's diverticulum and the ileocecal
      junction. Anlage of bursal follicles first appeared at E13 and developed
      thereafter. Immigration of Bu-1(+) cells to bursal follicles began at E13, and
      the number of Bu-1(+) cell subsequently increased. When the follicle of BF was
      eliminated from the embryo by treatment with testosterone, development of PP and
      CT were observed. We concluded therefore that the development of PP and CT start
      during late embryogenesis at the same time as the follicle of BF, and that
      appearance of surface IgM(+) cells in PP and CT is independent form the
      development of the follicle of BF.

PMID- 12808214
TI  - Effect of sustained release isosorbide dinitrate (EV151) in dogs with
      experimentally-induced mitral insufficiency.
AB  - To investigate the hemodynamic effects on seven anesthetized dogs with
      experimentally-induced mitral insufficiency, isosorbide dinitrate (ISDN) in
      sustained release form (EV151) was administered at different dosages (0, 2, 8 and
      16 mg/kg). The drug administration resulted in altered pulmonary arterial wedge
      pressure (preload), and cardiac output and total systemic resistance (afterload).
      Arterial pressure increased in the control group and in animals receiving 2
      mg/kg, but decreased in animals 1-2 hr after receiving 8 and 16 mg/kg dosages.
      Cardiac output increased in animals receiving 2, 8 and 16 mg/kg dosages, with
      concomitant decreases in total systemic resistance. ISDN caused mild vasodilation
      at 2 mg/kg and severe vasodilation at 8 and 16 mg/kg. Future experiments on non
      anesthetized dogs may be of benefit.

PMID- 12808215
TI  - Contraceptive effect of proligestone on spotted seals and crossbreeds of spotted
      seals and harbor seals.
AB  - Spotted seals (Phoca largha) and related crossbreeds maintained at Kamogawa Sea
      World breed seasonally from the end of January to middle of March. For
      contraception in these animals, the effect of a single administration of a
      contraceptive synthetic luteal hormone for dogs, proligestone (PRG), was
      investigated. The animals tested were 10 seals aged 4-24 years old, and a total
      of 35 trials were performed over five years. PRG was administered in 23 trials
      during January, which was one month before the estimated estrus, and in 12 trials
      during December of the previous year, which was two months before the estimated
      estrus. The dose of PRG was 5 mg/kg in 32 trials and 10 mg/kg in 3 trials. The
      effect of the contraception was judged by the presence or absence of delivery.
      Among 23 animals treated in January, 2 animals treated with 5 mg/kg PRG became
      pregnant, but the contraception was successful in the other 21 animals.
      Contraception was successful in all 12 trials treated with 5 mg/kg PRG in
      December. Overall, contraception was successful in 94.3% (33/35). Therefore, a
      single administration of 5 mg/kg PRG in December may be an effective method of
      contraception for seals.

PMID- 12808216
TI  - Diseases and outcomes in rabbits with high BUN levels.
AB  - One hundred and ninety cases of rabbits, seen at animal hospitals in Saitama and
      Tokyo, Japan from 1998 to 2001, with BUN values greater than 27 mg/dl were
      analyzed regarding their underlying and/or complicating diseases and outcomes.
      Gastrointestinal disorder (54 cases) was the most common disease, followed by
      overgrowth of molar teeth and then liver disturbance. The total mortality was
      48.9% within three months, and cases showing complications such as liver
      disturbance or bacterial infection showed highest mortality. Cases with higher
      BUN values showed even higher mortality, although mortality varied depending on
      the complications. Therefore, the prognosis of rabbit cases with high BUN values
      should be evaluated based on findings from blood chemistry, together with the
      seriousness of the underlying and/or complicating disease.

PMID- 12808217
TI  - Increased plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1)
      and soluble vascular cell molecule-1 (sVCAM-1) associated with disease severity
      in a primate model for severe human malaria: Plasmodium coatneyi-Infected
      Japanese macaques (Macaca fuscata).
AB  - In the present study, we investigated plasma levels of soluble intercellular
      adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in
      seven Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi.
      Concentrations of sICAM-1 and sVCAM-1 were significantly elevated in the severe
      phase; the levels were maximally increased up to six times and three times those
      before infection, respectively. We subsequently examined kinetic profiles of
      sICAM-1 and sVCAM-1 concentration in plasma obtained from two infected monkeys.
      Both infected monkeys had markedly increased levels of these adhesion molecules
      when they exhibited severe clinical signs correlated with rapid increase in
      parasitemia. These results suggest that the elevation of levels of sICAM-1 and
      sVCAM-1 is a critical step in the pathogenesis of severe malaria in vivo.

PMID- 12808218
TI  - Characterization of vpr vector constructed from chimeric simian and human
      immunodeficiency virus.
AB  - Chimeric simian and human immunodeficiency viruses (SHIVs) are useful tool for
      investigating AIDS pathogenesis and for development of vaccine. We constructed a
      SHIV-vpr vector (designated as SHIV-3sj) by replacing vpr region with restriction
      enzyme sites. SHIV-3sj was designed to express inserted gene along with its viral
      replication. Five cytokine genes were inserted into SHIV-3sj, and ability of
      viral replication and expression of the inserted genes were examined. The short
      insert including RANTES and IL-5 resulted in the successful expression from SHIV
      3sj, while the construct having longer genes including IL-2, IL-6 and IL-12p35
      failed to become replication competent. These results suggest that the length of
      the insert is an important factor for the replication ability of SHIV-3sj vector.

PMID- 12808219
TI  - Rabbit syphilis diagnosed clinically in household rabbits.
AB  - This paper deals with 16 cases presented from April to December 2001 and
      diagnosed clinically as rabbit syphilis, because they showed distinct lesions
      around the nose and/or mouth, responded to chemotherapy, and the "Rapid Plasma
      Reagin" test was positive. Twelve cases exhibited initial symptoms and four were
      relapses. Lesions around the genitalia and/or anus as well as the nose and/or
      mouth were seen in 8 cases, and 6 cases indicated sneezing. Fifteen cases were
      successfully treated with oral administration of chloramphenicol, and one was
      treated with long-acting penicillin by intramuscular injection. The mean age of
      onset was 8.8 months. As none of these cases had any mating history, the disease
      was likely to be maternally transmitted.

PMID- 12808220
TI  - Clinical usefulness of propofol as an anesthetic induction agent in dogs and
      cats.
AB  - Propofol was used as an induction agent of general anesthesia in 77 dogs and 64
      cats, all client owned, for a variety of surgeries/treatments or diagnostic
      procedures. The mean intravenous doses of propofol required to achieve
      endotracheal intubation in dogs and cats were 6.5 +/- 1.4 mg/kg and 10.1 +/- 2.8
      mg /kg, respectively. Most of the animals could be induced to anesthesia smoothly
      by the administration of propofol with a high incidence of apnea. Propofol is a
      clinically valuable anesthetic induction agent in both dogs and cats, however,
      care must be taken for apnea.

PMID- 12808221
TI  - Molecular cloning of equine muscle-type phosphofructokinase cDNA.
AB  - The complete coding region sequence of equine muscle-type phosphofructokinase
      (ePFKM) was obtained from skeletal muscle of a thoroughbred horse. The deduced
      amino acid sequence of ePFKM showed 97%, 96%, 96%, 96% and 95% identity to
      canine, human, mouse, rabbit and rat PFKM, respectively. The amino and carboxyl
      terminal halves of ePFKM presented a structure of tandem repeat, as other
      mammalian PFKMs. As the amino acid residues constituting various ligand-binding
      sites were also conserved, it is thought that ePFKM has enzymatic activity
      similar to PFKM in other mammals.

PMID- 12808223
TI  - Deformed liver with prominent proliferation of bile ducts in a pig.
AB  - A deformed liver characterized by remarkable ductular proliferation was
      encountered in a 6-month-old pig and examined histopathologically. The most
      conspicuous histopathologic change was a mild to severe ductular proliferation in
      the interlobular areas without any degenerative changes of cholangiolar
      epithelial cells or hepatocytes. Fibrotic changes and reconstruction of the
      lobule were not found. Morphological evidence of intrahepatic and extrahepatic
      cholestasis was lacking. Other characteristics were deformity with displacement
      of the gall bladder, irregular shape and size of lobules, and structural
      abnormality of large-sized vessels. The severe ductular proliferation was
      considered to be due to structural malformations of the excretion channel of
      bile.

PMID- 12808222
TI  - Identification of endotrypanum species from a sloth, a squirrel and Lutzomyia
      sandflies in ecuador by PCR amplification and sequencing of the mini-exon gene.
AB  - PCR amplification and nucleotide sequencing of the mini-exon gene revealed that
      four strains isolated from a sloth (Choloepus hoffmanni), a squirrel (Sciurus
      granatensis) and two sandflies (Lutzomyia hartmanni) in Ecuador were
      indistinguishable from Endotrypanum monterogeii. Another strain isolated from Lu.
      hartmanni showed the high sequence similarity to E. schaudinni. Since three of
      these strains have been previously identified as Leishmania (Viannia)
      equatorensis, the results demonstrate that L. (V.) equatorensis is genetically
      closely related to the genus Endotrypanum. The present study also indicates that
      Endotrypanum species are distributed in arboreal animals and sandflies in
      Ecuador, and that mini-exon gene amplification is useful for epidemiological
      studies of Leishmania and Endotrypanum in the New World.

PMID- 12808224
TI  - Intratubal insemination with fresh semen in dogs.
AB  - The number of spermatozoa required to obtain conception by intratubal
      insemination in dogs was examined. Three groups consisting of 5, 8 and 8 dogs
      received 0.5 x 10 (6), 2.0 x 10(6) and 4.0 x 10(6) spermatozoa, respectively,
      into each uterine tube. No conception occurred in the 5 animals inseminated with
      0.5 x 10(6) spermatozoa, but conception occurred in 6/8 (75.0%) and 3/8 (37.5%)
      dogs inseminated with 2.0 x 10(6) and 4.0 x 10 (6) spermatozoa, respectively.
      Among the pregnant animals, three aborted (33.3%) and the mean number of newborns
      was small, 2.5 +/- 0.5 (SE). One acardiacus anceps was observed with normal fetus
      in one animal with a Caesarean delivery.

PMID- 12808225
TI  - The effect of combined aerobic and resistance exercise training on abdominal fat
      in obese middle-aged women.
AB  - The purpose of this study was to investigate the effect of combined aerobic and
      resistance training on abdominal fat. Our participants in the study consisted of
      thirty obese women. They were separated into three groups: a control group
      (n=10), an aerobic training group (n=10) and a combined training group (n=10).
      The aerobic training group was composed of 60-70% HRmax (intensity), 60 minutes a
      day (duration) for 6 days a week (frequency). The combined training group was
      separated into resistance training (3 days a week, Mon, Wed, Fri) and the aerobic
      training (3 days a week, Tue, Thu, Sat). The levels for abdominal fat volume were
      measured by determining the subcutaneous fat volume (SFV), visceral fat volume
      (VFV), and VFV/SFV by CT (computed tomography). The VO(2max) was significantly
      (p<0.05) increased in both groups. The subcutaneous fat and visceral fat levels
      were decreased in the combined training group more than in the aerobics training
      group. Also, the lean body mass (LBM) was significantly increased only in the
      combined training group. In addition, the total cholesterol, triglyceride and LDL
      C were significantly (p<.05) decreased and the HDL-C was significantly (p<.05)
      increased in both groups. In conclusion, our results observed that combined
      training decreased abdominal subcutaneous fat and visceral fat more than aerobic
      training only.

PMID- 12808226
TI  - Does the regional oxygen uptake measured by near infrared spectroscopy reflect
      the phase II pulmonary oxygen uptake at the onset of exercise?
AB  - It has been hypothesized that the signals of near infrared spectroscopy (NIRS)
      would reflect muscle O(2) uptake (mVO(2)). Although it is not definite that NIRS
      signals accurately reflect mVO(2), there is every possibility that NIRS signals
      at least reflect regional O(2) uptake (rVO(2)). The phase II kinetics of
      pulmonary oxygen uptake (pVO(2)) is regarded as reflecting mVO(2) at the onset of
      exercise. To examine whether the rVO(2) on-kinetics measured by NIRS reflects the
      mVO(2) on-kinetics at the onset of exercise, we compared the rVO(2) as measured
      by NIRS with the phase II kinetics of pVO(2) at the onset of exercise. Twelve
      healthy male subjects cycled a Monark ergometer at three different intensities:
      below the ventilatory threshold (VT) level (below-VT), on the VT level (on-VT),
      and above the VT level (above-VT), for 6 minutes on three separate occasions. The
      rVO(2) was calculated from the concentration of oxyhemoglobin and
      deoxyhemoglobin, as measured by NIRS every 3 seconds. The pVO(2) was determined
      by the breath-by-breath method. A significant relationship between the amount of
      increases of pVO(2) and rVO(2) from rest to the end of exercise among all levels
      of exercise intensity was found (r=0.935, P<0.001). The time constants of rVO(2)
      (rVO(2)-Tc: below-VT: 6.514+/-2.159 s, on-VT: 7.760+/-2.035 s, above-VT: 9.532+/
      2.342 s) were significantly faster than the time constants of pVO(2) (pVO(2)-Tc:
      below-VT: 23.8+/-4.4 s, on-VT: 25.9+/-5.1 s, above-VT: 26.3+/-5.7 s) (P<0.001).
      There was no significant relationship between rVO(2)-Tc and pVO(2)-Tc for each
      intensity (P>0.05). We conclude that the rVO(2) on-kinetics measured by NIRS does
      not necessarily reflect the mVO(2) kinetics at the onset of exercise.

PMID- 12808227
TI  - Change in double product during stepwise incremental exercise.
AB  - The purpose of this study was to observe the change in double product with
      increases in the intensity of bicycle exercise. Eleven young male adults
      participated in this study. The subjects performed graded bicycling exercise
      increasing 20 watts every 2 min from 0 watts until the heart rate (HR) reached
      170 beats.min(-1). During exercise systolic blood pressure (SBP) and HR were
      continuously measured. Initially SBP gradually increased with the increase in
      workload, but when the intensity of exercise became even higher, the rate of
      increase slowed. On the other hand, the increase in HR was very small during the
      initial 5 min of exercise and when the intensity of exercise increased, the rate
      of increase of HR became higher. The polygonal regression analyses on the
      relation of double product to elapsed time revealed clear break-points. On
      average, the break-point of double product was 6.6 min (56 watts). These results
      clearly showed that the break-point of double product with an increase in
      workload appeared even though the workload was relatively low.

PMID- 12808228
TI  - Muscular performance modeling of the upper limb in static postures.
AB  - The purpose of the present paper is to describe and evaluate the polynomial
      models for predicting the muscular work capacity of the upper limb during
      sustained holding tasks. This research was concerned with the relationship
      between indicators of performance, i.e., specific posture or specific level of
      maximum voluntary contraction (MVC), and then modeling the functional data based
      on experimental results to estimate factors that may have an effect on task
      performance. To this end, we designed an experiment using 10 subjects in which
      each subject performed sustained isometric shoulder and elbow flexion endurance
      exercise under 27 conditions [3 shoulder angles (SA)x3 elbow angles (EA)x3 levels
      of %MVC]. Throughout all experiments, subjective perception of effort was
      assessed using the Borg scale, every 60, 30, and 10 s during the 20%, 40%, and
      60% MVC tests, respectively. Proposal models were represented by three
      approaches: model A: estimation of endurance time (ET), with input variables such
      as SA, EA, and %MVC; model B: estimation of recommendation time (RT, the time
      during which the operator was able to maintain a position under the desired
      condition), with input variables such as SA, EA, %MVC, and required rate on the
      Borg scale; and model C: estimation of limit strength or %MVC, with input
      variables such as SA, EA, request limit time for work (LT), and required rate on
      the Borg scale. Statistical analysis indicated that the three proposal estimation
      models based on polynomial regression functions showed high significance
      (p<0.0001). The proposal models suggested and recommended the possibility of
      finding the best positions entailing the reduction and minimization of total
      muscular strain from manual material handling tasks in different work situations,
      with the consequent increase in work efficiency.

PMID- 12808229
TI  - Relationships between depression, lifestyle and quality of life in the community
      dwelling elderly: a comparison between gender and age groups.
AB  - This study aimed to comprehensively investigate the comprehensive relationships
      between depression and the characteristics of lifestyle and quality of life (QOL)
      of healthy, community dwelling elderly, and compare them according to gender and
      age groups. 1302 subjects (657 males and 645 females) were used for analysis. The
      investigators in this study were researchers working at universities in each
      prefecture. Data collection was conducted in a general delivery survey and
      interview setting or an education class setting. The geriatric depression scale
      (GDS) consisting of 15 items with a dichotomous scale was used to assess
      depression symptoms in the elderly. In addition, 16 items selected from the four
      factors of economic situation, physical health, social activity, and personal
      status were used to assess lifestyle. Furthermore, this study investigated life
      satisfaction, morale, and physical function with the LSI scale, PGC morale scale
      and the ADL scale of the Ministry of Education, Science and Culture,
      respectively. According to our results, depression characteristics of the elderly
      differ between gender and age groups. Depression increases in the old-old elderly
      rather than in the young-old elderly and is highest in old-old females. The
      factors significantly related to depression in community dwelling elderly were
      the number of friends and morale. In particular, an increase in the number of
      friends was related to a decrease in depression. Depression in the old-old
      elderly was more significantly related to many lifestyle items compared with the
      young-old elderly, and especially in the old-old elderly, the extent of social
      activities related to a decrease in depression.

PMID- 12808230
TI  - Hepatic stellate cells: unique characteristics in cell biology and phenotype.
AB  - Hepatic stellate cells (HSCs), a mesenchymal cell type in hepatic parenchyma,
      have unique features with respect to their cellular origin, morphology, and
      function. Normal, quiescent HSCs function as major vitamin A-storing cells
      containing over 80% of total vitamin A in the body to maintain vitamin A
      homeostasis. HSCs are located between parenchymal cell plates and sinusoidal
      endothelial cells, and extend well-developed, long processes surrounding
      sinusoids in vivo as pericytes. However, HSCs are known to be 'activated' or
      'transdifferentiated' to myofibroblast-like phenotype lacking cytoplasmic lipid
      droplets and long processes in pathological conditions such as liver fibrosis and
      cirrhosis, as well as merely during cell culture after isolation. HSCs are the
      predominant cell type producing extracellular matrix (ECM) components as well as
      ECM degrading metalloproteases in hepatic parenchyma, indicating that they play a
      pivotal role in ECM remodeling in both normal and pathological conditions. Recent
      findings have suggested that HSCs have a neural crest origin from their gene
      expression pattern similar to neural cell type and/or smooth muscle cells and
      myofibroblasts. The morphology and function of HSCs are regulated by ECM
      components as well as by cytokines and growth factors in vivo and in vitro. Liver
      regeneration after partial hepatectomy might be an invaluable model to clarify
      the HSC function in elaborate organization of liver tissue by cell-cell and cell
      ECM interaction and by growth factor and cytokine regulation.

PMID- 12808231
TI  - The induction of apoptosis by methotrexate in activated lymphocytes as indicated
      by fluorescence hyperpolarization: a possible model for predicting methotrexate
      therapy for rheumatoid arthritis patients.
AB  - The objectives of this study were to test the in vitro response of healthy non
      activated, activated, and rheumatoid arthritis (RA) lymphocytes to methotrexate
      (MTX), and design an in vitro model for predicting the efficiency of MTX
      treatment for RA patients. Considering the RA profile of clonal-expanded CD4(+) T
      cells, phytohemagglutinin-activated mononuclear cells taken from healthy donors
      were incubated with different concentrations of MTX. The MTX-immunosuppressive
      effect was tested by fluorescence intensity measurements, including PI assay and
      annexin V assay. For simple detection, we used the Individual Cell Scanner (IC
      S), which enables the measurement of early events in individual cells. Healthy
      mononuclear cells (MNC), and MNC derived from RA patients, were tested by the IC
      S while utilizing fluorescence polarization (FP) measurements of fluorescein
      diacetate (FDA) as an established marker of activation or suppression. In healthy
      activated MNC, we found that MTX, through its early incubation period, interferes
      with the activation signal obtained by PHA and exerts an apoptotic signal, which
      is noted by increases in the FP. Comparing our model to six long-standing RA
      patients and five newly-diagnosed patients revealed significant differences in
      the FP measurements, including fluorescence depolarization as an early
      established measurement of lymphocyte activation, and hyperpolarization as a
      measurement of an early immunosuppressive effect. We conclude that MTX, an
      effective therapy for RA patients, could easily be tested by fluorescence
      polarization measurements of FDA before (or during) clinical use in order to
      predict its efficiency on a specific RA patient. Moreover, the FP measurements
      can be used for the diagnosis, and making timing and dosage decisions.

PMID- 12808232
TI  - Phenylarsine oxide and H2O2 plus vanadate induce reverse translocation of phorbol
      ester-activated PKCbetaII.
AB  - The intracellular localization of protein kinase C (PKC) is important for the
      regulation of its biological activity. Recently, it was reported that, whereas
      phorbol esters such as PMA induce prolonged translocation of PKC to the plasma
      membrane, with physiological stimuli, the translocation of PKC is transient and
      followed by rapid return to the cytoplasm. In addition, this membrane
      dissociation of PKC was shown to require both the kinase activity of PKC and the
      phosphorylation of its carboxyl terminus autophosphorylation sites. However, the
      detailed molecular mechanism of PKC reverse translocation remains obscure. We
      demonstrated that in porcine polymorphonuclear leucocytes (PMNs), phenylarsine
      oxide (PAO), a putative protein tyrosine phosphatase (PTPase) inhibitor, induced
      reverse translocation of PMA-stimulated PKCbetaII. Hydrogen peroxide (H(2)O(2))
      in combination with vanadate, both of which are PTPase inhibitors, also induced
      reverse translocation of PKCbetaII. H(2)O(2) or vanadate alone had little effect
      on PMA-induced PKCbetaII translocation. Furthermore, genistein and ethanol, which
      are inhibitors of tyrosine kinase and phospholipase D, respectively, prevented
      the PKCbetaII reverse translocation induced by the PTPase inhibitors. These
      results indicate, for the first time, that the tyrosine
      phosphorylation/phospholipase D pathway may be involved in the process of
      membrane dissociation of PKC.

PMID- 12808233
TI  - Functional characterization of bacterial signal peptide OmpA in a baculovirus
      mediated expression system.
AB  - Signal sequences are evolutionarily conserved and are often functionally
      interchangeable between prokaryotes and eukaryotes. However, we have found that
      the bacterial signal peptide, OmpA, functions incompletely in insect cells. Upon
      baculovirus-mediated expression of chloramphenicol acetyltransferase (CAT) in
      insect cells, OmpA signal peptide led to the cytosolic accumulation of the CAT
      molecules in an aglycosylated, signal-peptide cleaved form, in addition to the
      secretion of the glycosylated CAT. When green fluorescent protein (GFP) was used
      as another reporter, the GFP molecules expressed from the OmpA-GFP construct was
      distributed primarily in the cytosol as aggresome-like structures. These results
      together suggest that, subsequent to the cleavage of OmpA signal peptide in the
      ER, some of the processed proteins are returned to the cytoplasm. Since the
      prototypical insect signal peptide, melittin, did not result in this ER-to
      cytosol dislocation of the reporter proteins, we proposed a model explaining the
      dislocation process in insect cells, apparently selective to the OmpA-directed
      secretory pathway bypassing the co-translational transport.

PMID- 12808234
TI  - Design and feasibility assessment of topically applied drug formulations for
      electroporation.
AB  - Few studies have been reported on the design of topical formulations consisting
      of electrodes and active drugs for electroporation as a means to increase skin
      permeability of the drugs, although many studies were reported for the effect of
      this physical means using aqueous drug solutions. We, therefore, designed a
      prototypic reservoir and matrix topical formulations that are suitable for
      electroporation in the present study. Plate-plate Ag electrodes and sodium
      diclofenac were used as model electrodes and the drug, respectively. The in vitro
      skin permeations of the drug obtained from the reservoir and matrix formulations
      were slightly higher than that from an aqueous suspension. This may be due to
      slightly higher electric field in the skin barrier for the presently designed
      formulations than that for the aqueous suspension. The present feasibility test
      suggests that these reservoirs and matrix formulations are useful prototypic
      topical formulations for electroporation application to improve the drug
      permeability through skin.

PMID- 12808235
TI  - Multiparticulate chitosan-dispersed system for drug delivery.
AB  - A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug
      reservoir and the drug release-regulating layer, was developed for drug delivery.
      The drug release-regulating layer is a mixture of water-insoluble polymer and
      chitosan powder. The drug is released from CDS pellets in all regions of the
      gastrointestinal tract (from the stomach to the colon). CDS pellets containing
      chitosan powder were designed to dissolve chitosan powder partly in the release
      regulating layer in the stomach and release part of drug. After passing through
      the stomach, the drug is released from CDS pellets at a constant speed in the
      small intestine. In the large intestine, CDS pellets were designed to
      disintegrate the remaining chitosan powder at an accelerated speed and the
      remaining drug in CDS pellets is released. The drug release rate can be
      controlled with the thickness of the chitosan-dispersed water-insoluble layer.
      Furthermore, for colon-specific drug delivery, an additional outer enteric
      coating is necessary to prevent drug release from CDS pellets in the stomach,
      because the chitosan-dispersed water-insoluble layer dissolves gradually under
      acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to
      permit colon-specific drug delivery. In this study, the multiparticulate CDS was
      adopted not only for colon-specific drug delivery but also for sustained drug
      release.

PMID- 12808236
TI  - Synthesis and evaluation of guanidine-containing Schiff base copper(II),
      zinc(II), and iron(III) chelates as trypsin inhibitors.
AB  - 3-Formyl-4-hydroxyphenylguanidine hydrochloride and its Schiff base copper(II),
      zinc(II), and iron(III) chelates were synthesized and their inhibitory activity
      against bovine beta-trypsin were determined. Syntheses of Schiff base metal
      chelates were carried out from 3-formyl-4-hydroxyphenylguanidine, various L-amino
      acids, and divalent metal acetate. Their structures were established on the basis
      of spectroscopic evidence and elemental analysis. The inhibitory activity of
      these chelates against bovine beta-trypsin was determined. The guanidine
      containing copper(II) and zinc(II) chelates behaved as potent competitive
      inhibitors of trypsin. However, similar inhibitory activity was not observed for
      guanidine-containing iron(III) chelates. The inhibition constants (K(i) values,
      ca. 10(-5) M) of guanidine-containing Schiff base copper(II) and zinc(II)
      chelates were slightly lower than those (ca. 10(-6) M) of the corresponding
      amidine-containing Schiff base chelates with regard to bovine trypsin.

PMID- 12808237
TI  - Synthesis and anti-HIV-1 activity of novel 10-thiaisoalloxazines, a structural
      analog of C-5 and/or C-6 substituted pyrimidine acyclonucleoside.
AB  - A series of novel 10-thiaisoalloxazine derivatives bearing an alkoxymethyl or
      benzyloxymethyl moiety at the N-1 position has been synthesized through the
      bromination of 1-substituted-5-hydroxyuracils and subsequent condensation with
      aminobenzenethiol in a one-pot reaction. Contrary to the previous report, the
      formation of intermediary 5,6-diethoxy-5-hydroxy-5,6-dihydrouracil seems to be
      not the necessary factor for the formation of the thiaisoalloxazines, since the
      reaction proceeds in tetrahydrofuran (THF) or acetonitrile far more smoothly than
      in ethanol. The anti-human immunodeficiency virus (HIV)-1 activity of the
      resulted thiaisoalloxazine derivatives was evaluated in lymphocyte cells based on
      the inhibitory activity against the viral-induced cytopathic activity. Among the
      derivatives, compounds 6, 7, and 8 bearing an alkoxymethyl moiety at the N-1
      position exhibited modest inhibitory activity towards the cytotopathic effect of
      HIV-1.

PMID- 12808238
TI  - HPLC determination of (+)-pseudoephedrine and (-)-ephedrine in Japanese herbal
      medicines containing Ephedra herb using solid-phase extraction.
AB  - We developed a rapid and simple HPLC method combined with solid-phase extraction
      (SPE) for quantitative analysis of (+)-pseudoephedrine (PEP) and (-)-ephedrine
      (EP) in Japanese herbal (Kampo) medicines such as Kakkon-to, Sho-seiryu-to,
      Goshaku-san and Bofu-tsusho-san. SPE was performed on TOYOPAK IC-SP M containing
      propylsulfonic groups. Determination of PEP and EP was carried out using ion-pair
      reversed-phase HPLC with sodium dodecyl sulfate. N-Benzyldiethylamine was used as
      an internal standard. The analytical procedure was validated with regard to
      specificity, linearity, accuracy, and precision. These data suggest that the
      analytical method developed in this study is useful for quantitative analysis of
      PEP and EP in various formulations of Kampo medicine containing Ephedra herb.

PMID- 12808239
TI  - Synthesis and anti-tumor activity of new steroidal nuclear analogues of
      aragusterol A.
AB  - 3alpha,7alpha-Dihydroxy-5-epiaragusterol A (3) was synthesized from bile acid
      (cholic acid) as a new steroidal nuclear analogue of antitumor marine steroid
      aragusterol A. 7alpha-Hydroxyaragusterol A (4) was also derived from xestokerol
      B. The in vitro anti-proliferative activity of each of these analogues toward KB
      cells as well as in vivo anti-tumor activity of 5-epiaragusterol A (2) previously
      synthesized by the authors and 3 were assessed.

PMID- 12808240
TI  - Microbial metabolites of harman alkaloids.
AB  - Several microorganisms showed the ability to transform the harman alkaloids,
      harmaline (1), harmalol (2) and harman (5). Harmaline (1) and harmalol (2) were
      converted by Rhodotorula rubra ATCC 20129 into the tryptamines, 2-acetyl-3-(2
      acetamidoethyl)-7-methoxyindole (3) and 2-acetyl-3-(2-acetamidoethyl)-7
      hydroxyindole (4), respectively. Harman (5) was biotransformed by Cunninghamella
      echinulata NRRL 3655 into 6-hydroxyharman (6) and harman-2-oxide (7).

PMID- 12808241
TI  - Preparation of ternary platinum(II) complexes with N-(omega-phenylalkyl)-1,2
      ethanediamine and 2,2'-dipyridine and the effect of the methylene chain length of
      the N-(omega-phenylalkyl)-1,2-ethanediamine in the complexes on intermolecular
      interactions with various arylsulfonates.
AB  - A series of ternary complexes comprised of platinum(II), 2,2'-dipyridine, and N
      (omega-phenylalkyl)-1,2-ethanediamine was prepared by varying the number (n) of
      methylene chain carbons between the phenyl group and one of the amino groups of
      1,2-ethanediamine. NMR measurements indicated that intramolecular stacking
      occurred for n=1 and intermolecular stacking occurred for n=3 for several of the
      aryl sulfonates.

PMID- 12808242
TI  - Bioactive constituents from Chinese natural medicines. XI. inhibitors on NO
      production and degranulation in RBL-2H3 from Rubia yunnanensis: structures of
      rubianosides II, III, and IV, rubianol-g, and rubianthraquinone.
AB  - Three new arborinane-type triterpene glycosides, rubianosides II, III, and IV, a
      new arborinane-type triterpene, rubianol-g, and a new anthraquinone,
      rubianthraquinone, were isolated from a Chinese natural medicine, the roots of
      Rubia yunnanensis. The structures of the new constituents including their
      absolute configurations were determined on the basis of chemical and
      physicochemical evidence. The inhibitory effects of the isolated constituents on
      nitric oxide production in lipopolysaccharide-activated macrophages were
      examined. Among them, a cyclic peptide constituent, RA-XII and its aglycon, RA-V
      (deoxybouvadin), potently inhibited overproduction of nitric oxide and induction
      of inducible nitric oxide synthase. In addition, an anthraquinone constituent, 2
      methyl-1,3,6-trihydroxy-9,10-anthraquinone, was found to show inhibitory effects
      on the release of beta-hexosaminidase in RBL-2H3 cells.

PMID- 12808243
TI  - Effect of sodium tetraborate (borax) on the thermal properties of frozen aqueous
      sugar and polyol solutions.
AB  - The effect of sodium tetraborate (Na(2)B(4)O(7), borax) on the thermal property
      of frozen aqueous sugar and polyol solutions was studied through thermal
      analysis. Addition of borax raised the thermal transition temperature (glass
      transition temperature of maximally freeze-concentrated solutes; T(g)') of frozen
      sucrose solutions depending on the borax/sucrose concentration ratios. Changes in
      the T(g)' of frozen mono- and disaccharide solutions suggested various forms of
      complexes, including those of a borate ion and two saccharide molecules. Borax
      exerted the maximum effect to raise the oligosaccharide and dextran T(g)'s at
      borax/saccharide molar ratios of approximately 1-2 (maltose and
      maltooligosaccharides), 2 (dextran 1060), 5 (dextran 4900), and 10 (dextran
      10200). Further addition of borax lowered T(g)'s of the saccharide solutions.
      Borax also raised T(g) and T(g)' temperatures of frozen aqueous glycerol
      solutions. The decreased solute mobility in frozen solutions by the borate-polyol
      complexes suggested higher collapse temperature in the freeze-drying process and
      improved stability of biological systems in frozen solutions.

PMID- 12808244
TI  - Super acid-induced Pummerer-type cyclization reaction: improvement in the
      synthesis of chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines.
AB  - Improved synthesis of four stereoisomeric chiral 1,3-dimethyl-1,2,3,4
      tetrahydroisoquinolines (1a, b, ent-1a, b) was achieved via the super acid
      induced cyclization of chiral N-[1-methyl-2-(phenylsulfinyl)ethyl]-N-(1
      phenylethyl)formamides (4a, b, ent-4a, b) using the Pummerer-type cyclization
      reaction as a key step. The cyclization leading to the isoquinoline ring
      proceeded in a quantitative manner when trifluoromethane sulfonic acid (TFSA) was
      used as the super acid, although Friedel-Crafts-type alkylation of 4
      phenylsulfanyl TIQ derivatives (5) with benzene used as the solvent accompanied
      cyclization to yield the 4-phenyl-TIQs (7). The byproduct (7) was exclusively
      formed when a large excess amount of TFSA was used.

PMID- 12808245
TI  - Glycosides of Atractylodes lancea.
AB  - Five sesquiterpenoid glycosides (two guaiane-type glycosides and three eudesmane
      type glucosides) and a glucoside of an acetylene derivative were newly isolated
      from the water-soluble portion of the methanolic extract of Atractylodes lancea
      rhizome together with 26 known compounds. Their structures were characterized as
      atractyloside A 14-O-beta-D-fructofuranoside, (1S,4S,5S,7R,10S)-10,11,14
      trihydroxyguai-3-one 11-O-beta-D-glucopyranoside, (5R,7R,10S)-isopterocarpolone
      beta-D-glucopyranoside, cis-atractyloside I, (2R,3R,5R,7R,10S)-atractyloside G 2
      O-beta-D-glucopyranoside, and (2E,8E)-2,8-decadiene-4,6-diyne-1,10-diol 1-O-beta
      D-glucopyranoside on the basis of chemical and spectroscopic investigation. The
      presence of six characteristic guaiane-type glucosides in both rhizomes of A.
      lancea and Atractylodes japonica suggested a close chemotaxonomic relationship
      between them.

PMID- 12808246
TI  - Wild ginseng grows in Myanmar.
AB  - Ginseng, the underground parts of plants of Panax species, has been used in
      oriental traditional medicine for centuries. Unfortunately, because of extensive
      exploitation over thousands of years, the natural source of these species has
      been almost exhausted. Recently, we have found a wild ginseng growing in Myanmar.
      Here, by a combination of chemical composition study and gene sequence analysis,
      we unambiguously demonstrate that the wild ginseng is actually P. zingiberensis,
      commonly known as ginger ginseng. This ginseng was an indigenous to the
      southwestern China. However, now it is seriously threatened to brink of
      extinction and is put on the highest level of protection in China. Therefore, an
      appropriate protection measure is highly recommended to preserve this valuable
      resource, since this Myanmar ginseng might turn out to be the last P.
      zingiberensis, which could ever be seen in the planet.

PMID- 12808247
TI  - Four new cycloartane glycosides from Aquilegia vulgaris and their
      immunosuppressive activities in mouse allogeneic mixed lymphocyte reaction.
AB  - Four new cycloartane glycosides, named aquilegiosides C-F, were isolated from the
      dried aerial parts of Aquilegia vulgaris. Their structures were determined by two
      dimensional (2D) NMR spectroscopic analysis and chemical evidence. Aquilegiosides
      C-F suppressed the proliferation of lymphocytes in mouse allogeneic mixed
      lymphocyte reaction with IC(50), ranging from 3.7x10(-5) to 2.2x10(-4) M.

PMID- 12808248
TI  - Atropisomers of 1-(acyl or aroyl)-2-naphthylindolines. Isolation, X-ray crystal
      structure and conformational analysis.
AB  - A series of pairs of stable diastereomeric atropisomers caused by restricted
      rotation around the Csp3-Csp2 bond of [2-(2-hydroxynaphthalen-1-yl)-3,3-dimethyl
      2,3-dihydroindol-1-yl]-(3- or 4-substituted phenyl)-methanone or [2-(2
      hydroxynaphthalen-1-yl)-3,3-dimethyl-2,3-dihydroindol-1-yl]-1-alkanone were
      isolated. The conformational analyses of the atropisomers were performed based on
      the X-ray crystallographic and (1)H-NMR spectral data. It became clear that
      rotation about the C2-naphthyl bond is restricted at room temperature, whereas
      the >NCO-Ar bond rotates freely.

PMID- 12808249
TI  - Structure-activity relationships of 2-(benzothiazolylthio)acetamide class of CCR3
      selective antagonist.
AB  - The structure activity relationships of novel selective CCR3 receptor
      antagonists, 2-(benzothiazolylthio)acetamimde derivatives were described. A lead
      structure (1a) was discovered from the screening of the focused library that was
      based on the structure of our dual antagonists for the human CCR1 and CCR3
      receptors. Derivatization of 1a including incorporation of substituent(s) into
      each benzene ring of the benzothiazole and piperidine side chain resulted in the
      identification of potent and selective compounds (1b, r, s) exhibiting nano-molar
      binding affinity (IC(50)s: 1.5-3.0 nM) and greater than 800-fold selectivity for
      the CCR3 receptor over the CCR1 receptor.

PMID- 12808250
TI  - Application of the Lewis acid-Lewis base bifunctional asymmetric catalysts to
      pharmaceutical syntheses: stereoselective chiral building block syntheses of
      human immunodeficiency virus (HIV) protease inhibitor and beta3-adenergic
      receptor agonist.
AB  - Chiral building block syntheses of promising drugs were achieved using two types
      of catalytic stereoselective cyanosilylations of aldehydes promoted by Lewis acid
      Lewis base bifunctional catalysts 1 and 2 as the key steps (diastereoselective
      cyanosilylation of amino aldehyde and enantioselective cyanosilylation). In the
      first part of this article, syntheses of chiral building blocks (6) of Atazanavir
      (3: human immunodeficiency virus (HIV) protease inhibitor) using the bifunctional
      catalyst 2 are discussed. The reaction of Boc-protected phenylalaninal 21 in the
      presence of 1 mol% catalyst 2 selectively afforded the anti isomer 22 as the
      major product (diastereomeric ratio=97 : 3), which was successively converted to
      the corresponding epoxide 6 in six steps. In the second part, we describe a
      chiral building block synthesis of beta(3)-adrenergic receptor agonists. The
      enantioselective cyanosilylation of 3-chlorobenzaldehyde (38) with 9 mol%
      catalyst 1 gave the chiral cyanohydrin 39, which was converted to beta
      hydroxyethylamine 40 by reduction. Moreover, the chiral ligand of catalyst 1
      could be recovered without column chromatography and reused without decreasing
      its activity.

PMID- 12808251
TI  - Phylogenetic relationship of psychoactive fungi based on the rRNA gene for a
      large subunit and their identification using the TaqMan assay.
AB  - "Magic mushrooms" (MMs) are psychoactive fungi containing the and Psychotropics
      Control Law in Japan. Because there are many kinds of MMs and they are often sold
      even as dry powders in local markets, it is very difficult to identify the
      original species of the MMs by morphological observation. Therefore, we
      investigated the rRNA gene for a large subunit (LSU) of several MMs to classify
      them by a genetic approach. In this paper, we described the phylogeny of species
      of MMs based on the partial sequence (about 970 bp) of the LSU and the rapid
      identification of MMs using the TaqMan PCR assay.

PMID- 12808252
TI  - A simple HPLC method for simultaneous determination of lopinavir, ritonavir and
      efavirenz.
AB  - We developed a simple HPLC method for the simultaneous determination of lopinavir
      (LPV), ritonavir (RTV) and efavirenz (EFV) to evaluate the efficiency of co
      administration of LPV/RTV and EFV in Japanese patients enrolled in a clinical
      study. The monitoring of LPV plasma concentration is important because co
      administration of LPV/RTV with EFV sometimes decreases plasma concentrations of
      LPV caused by EFV activation of cytochrome P-450 3A. A solution of acetonitrile,
      methanol and tetramethylammonium perchlorate (TMAP) in dilute aqueous
      trifluoroacetic acid (TFA) has been used as the mobile phase in a HPLC method to
      elute LPV and RTV. We found that a solvent ratio of 45 : 5 : 50 (v/v/v) of
      acetonitrile/methanol/0.02 M TMAP in 0.2% TFA optimized separation of LPV, RTV
      and EFV. A column temperature of 30 degrees C was necessary for the
      reproducibility of the analyses. Standard curves were linear in the range 0.060
      to 24.06 micro g/ml for LPV, 0.010 to 4.16 micro g/ml for RTV, and 0.047 to 37.44
      micro g/ml for EFV. Coefficients of variation (CVs) of LPV, RTV and EFV in
      intraday and interday assays ranged from 1.5 to 4.0%, 2.5 to 16.8% and 1.0 to
      7.7%, respectively. Accuracies ranged from 100 to 110%, 101 to 116% and 99 to
      106% for LPV, RTV and EFV, respectively. The extraction recoveries were 77-87, 77
      83 and 81-91% for LPV, RTV and EFV, respectively.

PMID- 12808253
TI  - First natural urease inhibitor from Euphorbia decipiens.
AB  - Three new diterpene esters with a myrsinol-type skeleton have been isolated from
      Euphorbia decipiens BOISS. & BUHSE. The structure elucidation of the isolated
      compounds was based primarily on two-dimensional (2D)-NMR techniques including
      correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC),
      heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser effect
      spectroscopy (NOESY) experiments. Compounds 1 and 3 are active against prolyl
      endopeptidase and compound 2 showed inhibitory activity against urease enzyme.

PMID- 12808254
TI  - Isolation of peridinin-related norcarotenoids with cell growth-inhibitory
      activity from the cultured dinoflagellate of Symbiodinium sp., a symbiont of the
      Okinawan soft coral Clavularia viridis, and analysis of fatty acids of the
      dinoflagellate.
AB  - Two norcarotenoids, 1 and 2, related to peridinin (3) were isolated from the
      cultured dinoflagellate of the genus Symbiodinium, a symbiont of the Okinawan
      soft coral Clavularia viridis, which contains in abundance antitumor marine
      prostanoids such as clavulones. The structures of 1 and 2 were elucidated on the
      basis of spectroscopic analysis. These compounds showed significant growth
      inhibitory activity in vitro toward cancer cells. Analysis of fatty acids of the
      dinoflagellate was also carried out, suggesting that the marine prostanoids are
      produced by the host soft coral itself.

PMID- 12808255
TI  - Synthesis and evaluation of 5-Aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2-(3H)
      thiones as P-glycoprotein inhibitors.
AB  - 5-Aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 3 were prepared by
      cyclocondensation of 1-(4-hydroxyphenyl)-2-aroylhydrazines with thiophosgene. All
      compounds exhibited antiproliferation activity in K562, IC(50) ranging from 24 to
      94 micro M comparable efficacy with apigenin and genistein and showed more potent
      antiproliferation of K562/adr cells, highly expressing P-glycoprotein. Compounds
      3g, 3e and 3a inhibited the function of P-glycoprotein with the alpha(0.5) equal
      to 10+/-3 micro M, 21+/-5 micro M and 34+/-7 micro M, respectively.

PMID- 12808256
TI  - 1,3-dimethylisoguaninium, an antiangiogenic purine analog from the sponge
      Amphimedon paraviridis.
AB  - An antiangiogenic purine analog, 1,3-dimethylisoguaninium (1), was isolated from
      the ethanol (EtOH) extract of the Okinawan sponge Amphimedon paraviridis. The
      structure was elucidated on the basis of its spectral properties and X-ray
      crystallographic analysis. Compound 1 exhibited specific inhibition of the basic
      fibroblast growth factor (bFGF)-induced proliferation of bovine aorta endothelial
      cells (BAECs). Moreover, compound 1 reduced the tube formation of BAECs in a time
      dependent manner.

PMID- 12808257
TI  - Measurement of diffusion coefficients of parabens and steroids in water and 1
      octanol.
AB  - Diffusion coefficients (D) of parabens and steroids in water and 1-octanol were
      determined by using the chromatographic broadening method at 37 degrees C, and
      the relationships between the D values and the physicochemical properties of the
      drugs were discussed. The D values in 1-octanol were lower than those in water
      because of the higher viscosity of 1-octanol. The D values depend on not only the
      molecular weight (MW), but also the lipophilicity of the drugs in water and on
      the ability for hydrogen-bonding in 1-octanol. When the lipophilic index (LI),
      calculated from the retention time using in a reverse-phase column, was used as a
      parameter of drug lipophilicity, the following equation was obtained for D in
      water (D(w)); log D(w)=-0.215.log MW-0.077.log LI-4.367. When the hydrogen bond
      index (HI), the logarithm of the ratio of the partition coefficient of the drugs
      in 1-octanol and cyclohexane, was used as an index of hydrogen-bonding, the
      following equation was obtained for D in 1-octanol (D(o)); log D(o)=-0.690.log MW
      0.074.log HI-4.085.

PMID- 12808258
TI  - Wrightiamines A and B, two new cytotoxic pregnane alkaloids from Wrightia
      javanica.
AB  - Two new pregnane alkaloids, wrightiamines A (1) and B (2), were isolated from the
      extract of the tropical Apocynaceous plant Wrightia javanica collected in
      Thailand, and their structures were elucidated by spectral data. Wrightiamine B
      (2) was preparaed from 3beta-hydroxy-5alpha-pregnan-20-one to establish the
      configuration of the C-20 position as S. Wrightiamine A (1) exhibited cytotoxic
      activity against vincristine-resistant murine leukemia P388 cells.

PMID- 12808259
TI  - Direct evidence for the plant origin of Brazilian propolis by the observation of
      honeybee behavior and phytochemical analysis.
AB  - To identify the plant origin of Brazilian propolis directly, we observed the
      behavior of honeybees in Minas Gerais State of Brazil. Honeybee workers bit and
      chewed leaves of the plant, Baccharis dracunculifolia, packed the material into
      their pollen basket, brought it back to their nest, and used it as propolis. We
      collected the leaves of B. dracunculifolia and propolis, and compared their
      constituents by liquid chromatography-mass spectrometry (LC/MS) analysis. There
      was no difference between the chemical constituents of the ethanol extracts of B.
      dracunculifolia and those of propolis. This indicates directly that the plant
      origin of Brazilian propolis is B. dracunculifolia.

PMID- 12808260
TI  - Development of a novel granular detergent with an interspersion particle
      comprising an anionic surfactant and a polymeric polycarboxalate.
AB  - This paper discusses a process for making a novel granular detergent with an
      interspersion particle comprising an anionic surfactant and a polymeric
      polycarboxalate. This process contains three steps to develop the interspersion
      particles with anionic surfactant and polymeric ploycarboxalate. The first step
      was to form a detergent particle by spray drying of an aqueous detergent slurry
      comprising anionic surfactant (liner alkyl benzene sulfonate) with the different
      levels of polymeric polycarboxalate. In the second step, the spray-dried granules
      were densified and ground by a roll compacter and a grinder. The ground particles
      were coated by nonionic and zeolite in a vertical batch type high shear mixer
      (third step). In this study, the feasibility to make better performance of
      granular detergent was discussed.

PMID- 12808261
TI  - Reduction in serum total cholesterol and risks of coronary events and cerebral
      infarction in Japanese men: the Kyushu Lipid Intervention Study.
AB  - Lowering serum total cholesterol is shown to decrease the risk of coronary heart
      disease (CHD) in Western countries,but evidence is limited regarding cerebral
      infarction (CI). The present study used the Kyushu Lipid Intervention Study to
      examine the risks of CHD events and CI in relation to reduction in serum total
      cholesterol. Subjects were 4,615 men aged 45-74 years with serum total
      cholesterol of 220 mg/dl (5.68 mmol/L) or greater who had no history of CHD
      events or stroke. CHD events and CI numbered 125 and 92, respectively, in a 5
      year follow-up. After adjustment for potential confounding factors, the relative
      risks of CHD events and CI for 15% or greater reduction in total cholesterol,
      compared with less than 5% reduction, were 0.78 (95% confidence limit [CL]0.46
      1.32) and 0.39 (95% CL 0.22-0.69), respectively. As compared with on-treatment
      cholesterol levels of 240 mg/dl (6.20 mmol/L)or higher, the risk of CHD events
      was approximately 50% lower across 3 categories below 240 mg/dl (6.20 mmol/L),
      and that of CI was 70%lower at 2 categories below 220 mg/dl (5.68 mmol/L).
      Lowering serum total cholesterol below 220 mg/dl (5.68 mmol/L) seems desirable
      with regard to the prevention of CI.

PMID- 12808262
TI  - Body composition as a risk factor for coronary artery disease in Chinese type 2
      diabetic patients in Taiwan.
AB  - This study aimed to clarify whether body mass index (BMI), waist/hip ratio (WHR)
      or percent body fat (%fat) is associated with coronary artery disease (CAD) in
      Chinese type 2 diabetic patients in Taiwan. A total of 463 patients were
      recruited. BMI and WHR were measured by standard methods and %fat by
      bioelectrical impedance. CAD was diagnosed as acute myocardial infarction, angina
      pectoris, or an electrocardiogram showing 'coronary probable or possible'
      according to the Minnesota codes. Age, sex, diabetes duration, hypertension,
      smoking, fasting plasma glucose, hemoglobin A(1c),and serum concentrations of
      total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and
      low-density lipoprotein cholesterol were treated as confounders. Results showed
      that 144 patients had CAD. Age, hypertension, HDL-C and %fat were independently
      associated with CAD. CAD prevalence was 25.5%, 26.8%, 31.9% and 43.0%,
      respectively, for the first to fourth quartile of %fat (p<0.05). Multivariate
      adjusted odds ratio for CAD for every 1% increase in %fat was 1.02 (1.01-1.03);
      and 1.01 (0.73-1.88), 1.26 (0.69-2.32) and 2.11 (1.09-4.07) for the second to
      fourth quartile, respectively, compared with the first quartile. BMI and WHR were
      not associated with CAD in similar analyses. In conclusion, %fat was a better
      predictor for CAD than BMI and WHR in Chinese type 2 diabetic patients in Taiwan.

PMID- 12808263
TI  - Clinical significance of prolonged P wave width after right atrial appendage
      pacing in sick sinus syndrome.
AB  - The present study investigated both the clinical significance of atrial
      fibrillation (AF) before right atrial appendage (RAA) pacing and the influence of
      prolonged P wave on AF occurrence in RAA-paced patients with sick sinus syndrome
      (SSS). Fifty-seven patients (age 68+/-10 years; 19 men, 38 women) with SSS who
      underwent RAA pacing were divided into 2 groups: 23 patients without AF before
      pacing (I + II; Rubenstein I or II) and 34 patients with AF before pacing (III;
      Rubenstein III). The P wave duration in intrinsic rhythm and with RAA pacing were
      measured on the standard electrocardiography in leads II and V(1) with the use of
      a digitizing tablet. Group III was further subdivided into 2 groups: 20 patients
      (IIIb) with a paced P wave >130 ms in both leads II and V(1) and the other 14
      patients (IIIa). The duration of the intrinsic P wave in leads II and V(1) was
      significantly greater in group III than in group I + II (119+/-20 vs 108+/-21 ms,
      p=0.0417, 106+/-16 vs 95+/-21 ms, p=0.0258, respectively). During the follow-up
      of 40+/-21 months, AF recurrence was significantly higher in group IIIb than in
      groups IIIa and I + II (17/20 vs 5/14 vs 2/23 p<0.0001). A few occurrences of AF
      were observed by conventional RAA pacing in patients without AF before pacing.
      However, SSS with AF before pacing caused a significant intra-atrial conduction
      disturbance and a high incidence of AF recurrence after implantation of RAA
      pacing, especially in patients with a prolonged paced P wave, in whom new pacing
      modalities may be needed to shorten paced P wave duration and prevent AF.

PMID- 12808264
TI  - Narrowing of the left ventricular cavity associated with transient ventricular
      wall thickening reduces stroke volume in patients with acute myocarditis.
AB  - It has been reported that some patients with acute myocarditis have transient
      ventricular thickening associated with narrowing of the left ventricular cavity
      caused by interstitial edema. The present study investigated this phenomenon in
      20 patients with acute myocarditis. Based on the sum of the interventricular
      septal wall thickness and left ventricular posterior wall thickness (IVST + PWT),
      measured by M-mode echocardiography, patients were divided into group A (IVST +
      PWT >/=25 mm, n=12) and group B (IVST + PWT <25 mm, n=8). The IVST + PWT was 31.8
      +/-3.5 mm in group A and 21.9+/-2.7 mm in group B (p<0.0001). The left
      ventricular end-diastolic dimension (LVDd) was 42.3+/-6.0 mm in group A and
      49.4+/-6.7 mm in group B (p<0.05). The stroke volume (SV) was 41.1+/-20.5 ml and
      73.0+/-32.3 ml in groups A and B, respectively (p<0.05). The left ventricular
      ejection fraction (LVEF) was similar in group A (47.9+/-13.0%) and group B
      (56.9+/-9.0%). The SV correlated inversely with IVST + PWT (r=-0.62, p<0.01), and
      directly with both the LVDd (r=0.95, p<0.0001) and LVEF (r=0.64, p<0.01). The
      LVDd correlated inversely with IVST + PWT (r=-0.62, p<0.01). In conclusion, the
      reduction in SV that occurs during the acute phase of myocarditis is not only the
      result of systolic dysfunction, but also of the concentric left ventricular wall
      thickening associated with myocardial interstitial edema, which results in
      narrowing of the left ventricular cavity at end diastole.

PMID- 12808266
TI  - Beneficial effect of coronary artery bypass grafting as assessed by quantitative
      gated single-photon emission computed tomography.
AB  - The development of quantitative gated single-photon emission computed tomography
      (SPECT) has enabled the assessment of left ventricular perfusion, function and
      wall thickness in a single examination. Accordingly, the present study used gated
      SPECT to assess the benefit of coronary artery bypass grafting (CABG) in patients
      with coronary artery disease; 47 of those patients were evaluated before and 5
      months after CABG. As a result of coronary revascularization, a significant
      improvement was observed in global ejection fraction (50+/-12 --> 53+/-11%;
      p<0.05). In 107 revascularized territories, the average regional reversible
      defect score (0.8+/-0.5 --> 0.2 +/-0.3; p<0.0001), average regional perfusion
      score at rest (0.6+/-0.6 --> 0.3+/-0.4; p<0.0001), average regional wall motion
      score (0.9+/-0.7 --> 0.7+/-0.5; p<0.05), and end-diastolic wall thickness (8.1+/
      1.3 --> 8.6+/-1.5 mm; p<0.0005) all improved significantly. Even in 34 non
      revascularized territories, the average regional reversible defect score (0.5+/
      0.7 --> 0.2+/-0.5; p<0.03), average regional wall motion score (0.8+/-1.1 --> 0.5
      +/-1.0; p<0.03) and end-diastolic wall thickness (8.0+/-1.4 --> 9.1+/-2.0 mm;
      p<0.03) all improved significantly. These results indicate that improvement in
      myocardial ischemia, hibernation and left ventricular function with CABG can be
      assessed in detail with gated SPECT.

PMID- 12808265
TI  - Q-T peak dispersion in congenital long QT syndrome: possible marker of mutation
      of HERG.
AB  - Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac
      potassium or sodium channel genes, with 6 different genotypes thus far
      identified. However, it is unknown whether these genotypes can be differentiated
      by QT variables. The electrocardiograms obtained from 16 patients with a mutation
      in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control
      subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc)
      and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected
      interval from T peak to T end (Tpec) was measured in lead V(5). The maximum QTc,
      QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2
      patients than in the controls. However, there were no significant differences in
      these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion
      was significantly increased in the LQT2 patients (78+/-25 ms) compared with the
      LQT1 patients (29+/-15 ms) and controls (26+/-19 ms). These results suggest that
      increased lag of the peak of the T wave in each precordial lead (QTpc dispersion)
      may be a possible index to differentiate LQTS patients with HERG mutation from
      those with KCNQ1 mutation.

PMID- 12808267
TI  - Exercise training in patients with chronic heart failure improves endothelial
      function predominantly in the trained extremities.
AB  - The present study investigates whether lower-limb dominant exercise training in
      patients with chronic heart failure (CHF) improves endothelial function primarily
      in the trained lower extremities or equally in the upper and lower extremities.
      Twenty-eight patients with CHF were randomized to the exercise or control group.
      The exercise group underwent cycle ergometer training for 3 months while controls
      continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test)
      and flow-mediated vasodilation in the brachial and posterior tibial arteries were
      evaluated. After 3 months, walking performance increased only in the exercise
      group (488+/-16 to 501+/-14 m [control]; 497+/-23 to 567+/-39 m [exercise,
      p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change
      in either group (4.2+/-0.5 to 4.5+/-0.4% [control]; 4.3+/-0.5 to 4.6+/-0.4%
      [exercise]), but that in the posterior tibial arteries increased only in the
      exercise group (4.1+/-0.5 to 4.1+/-0.3% [control]; 3.6+/-0.3 to 6.4+/-0.6%
      [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation
      in the trained lower limbs, but not in the untrained upper limbs. Exercise
      training appears to correct endothelial dysfunction predominantly by a local
      effect in the trained extremities.

PMID- 12808268
TI  - Autonomic imbalance as a property of symptomatic Brugada syndrome.
AB  - The autonomic properties in 27 patients with the electrocardiographic morphology
      of Brugada syndrome were investigated using 24-h Holter monitoring: 10 patients
      had a history of ventricular fibrillation (VF; Br-VF group) and 17 did not (Br-N
      group); there were 26 healthy subjects enrolled in this study. All subjects
      underwent normal Holter data monitoring and power spectral analysis. Few
      extrasystoles were observed in either group, and the mean heart rate (HR),
      maximum HR, and total heart beats over 24 h were obtained. All of these
      measurements were significantly lower in the Br-VF group than in the Br-N and
      healthy subject groups. The RR interval variability was analyzed over 512 beats
      every 10 min. The high-frequency component (0.15-0.40 Hz; HF), low-frequency
      component (0.04-0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. The HF
      was significantly higher and LF/HF ratio lower in the Br-VF group than in the
      healthy subjects. The HF was also significantly higher than in the Br-N group.
      During the night (00.00-05.00 h), the HF was significantly higher in the Br-VF
      group, and the LH/HF lower. During the day (12.00-17.00 h), the HF was
      significantly higher in the Br-VF group, but there was no difference in the
      LF/HF. These results indicate that high vagal tone and low sympathetic tone are
      specific properties of symptomatic Brugada syndrome.

PMID- 12808269
TI  - Changes in evoked QT intervals according to variations in atrioventricular delay
      and cardiac function in patients with implanted QT-driven DDDR pacemakers.
AB  - In patients with implanted DDD pacemaker, cardiac output is maximal when
      atrioventricular (AV) delay is set to give the maximum QT interval (QTI). QTI is
      used as a sensor of a rate-responsive pacemaker and the evoked QTI (eQTI) is
      measured as the time duration from the ventricular pace-pulse and the T sense
      point, which is the steepest point of the intracardiac T wave. The relationship
      between the changes in eQTI according to AV delay variations and cardiac function
      was studied in 13 patients (74.2+/-9.3 [SD] years old) with an implanted QT
      driven DDDR-pacemaker. A special software module was downloaded into the
      pacemaker memory and a personal computer equipped with the special software was
      connected to the programmer for eQTI date-logging. AV delay was set at 100, 120,
      150, 180 and 210 ms. Delta eQTI was defined as maximal eQTI - minimal eQTI. The
      ejection fraction (EF) was measured by echocardiography. When the AV delay was
      prolonged, eQTI gradually increased and reached a peak, and then decreased. Delta
      eQTI in patients with reduced cardiac function (EF <40%) was significantly
      greater than that in normal cardiac function (EF >55%, 7.6+/-4.9 vs 2.7+/-9.8 ms,
      p<0.05). There was significant negative correlation between EF and delta eQTI (r=
      0.63, p<0.05). The peak of changes in eQTI according to AV delay variations was
      steeper in patients with reduced cardiac function than in those with normal
      cardiac function. In conclusion, changes in eQTI according to AV delay variation
      are greater in patients with reduced cardiac function than in those with normal
      cardiac function, and the AV delay that gives the maximal eQTI can be easily
      determined in patients with reduced cardiac function.

PMID- 12808270
TI  - Effects of candesartan and probucol on restenosis after coronary stenting:
      results of insight of stent intimal hyperplasia inhibition by new angiotensin II
      receptor antagonist (ISHIN) trial.
AB  - The purpose of this study was to determine whether candesartan and its
      combination with probucol reduce restenosis after coronary stenting. A total of
      132 patients who successfully underwent stenting were randomly assigned to a
      control group (n=45), a candesartan group (8 mg daily, n=43), or a candesartan
      plus probucol group (+ probucol 500 mg daily, n=44). No differences in late loss
      were observed between the control and candesartan groups. In the candesartan plus
      probucol group, late loss was significantly smaller than in the control and
      candesartan groups (p=0.003, 0.015). The restenosis rate was 27% in the control
      group, 26% in the candesartan group (p>0.99), and 11% in the candesartan plus
      probucol group (p=0.104 vs the control group and p=0.103 vs the candesartan
      group). Intravascular ultrasound revealed no differences in stent area among the
      3 groups, and no differences in lumen area or in intimal hyperplasia area between
      the control and candesartan groups. However, the intimal hyperplasia area in the
      candesartan plus probucol group was significantly less than that in the control
      and candesartan groups (p<0.001, p<0.001). This study demonstrated that
      candesartan failed to inhibit the neointimal hyperplasia and although the
      combination treatment did reduce neointimal hyperplasia, it did not statistically
      reduce the restenosis rate.

PMID- 12808271
TI  - Coronary flow--pressure relationship distal to epicardial stenosis.
AB  - To assess the coronary flow velocity - pressure relationship distal to a
      stenosis, and to evaluate the influence of microvascular abnormalities on this
      relationship, coronary flow velocity and coronary pressure were measured
      simultaneously in 38 patients (42 vessels). The instantaneous peak coronary flow
      velocity was plotted against the simultaneous measured distal coronary pressure,
      and the slope of the relation in the phase of diastolic flow decrease was
      calculated as the flow - pressure slope index (FPSI) and the X-intercept of the
      slope was calculated as zero-flow pressure (Pzf). The slope of the curve
      increased from 2.0+/-2.6 to 4.5+/-4.1 (p<0.001) and the X-intercept decreased
      from 42+/-16 to 27+/-13 mmHg (p<0.001) after papaverine injection. After
      successful coronary intervention, Pzf increased from 23+/-10 to 35+/-11 (p<0.01)
      and FPSI decreased from 6.8+/-5.1 to 3.5+/-1.8 (p<0.05). Pzf was higher in
      patients with an old myocardial infarction. It is feasible to assess the
      relationship between coronary flow and pressure distal to a stenosis in the
      clinical setting, and the relationship may provide additional information
      regarding coronary microcirculation. Microvascular abnormalities may play an
      important role in the coronary flow - pressure relationship distal to stenosis.

PMID- 12808272
TI  - Feasibility and effect on blood pressure of 6-week trial of low sodium soy sauce
      and miso (fermented soybean paste).
AB  - A double-blind, randomized placebo-controlled study was conducted to evaluate the
      feasibility of the long-term use of low-sodium soy sauce and miso in the general
      Japanese population and its effect on blood pressure (BP). Forty men and 24 women
      were randomly allocated to a low-sodium group (n=32) or a control group (n=32).
      Low-sodium soy sauce and miso, which were approximately 25% and 20% lower in salt
      content than common soy sauce and miso, were used in the study. The change in BP
      after a 6-week intervention was evaluated. There were no significant differences
      in age, sex, body mass index, BP or hypertension between the 2 groups before
      intervention. After the 6-week intervention, no significant change in BP was
      observed in the entire cohort. However, in those aged 40 years and older, 6.4
      mmHg net reduction in diastolic BP with no significant change in systolic BP was
      noted in the low-sodium group. Taste evaluation for the low-sodium seasoning was
      considerably good. Replacing soy sauce and miso of the common type with the low
      sodium alternative is feasible in the general population and could be the basis
      for a salt reduction strategy in the Japanese diet.

PMID- 12808273
TI  - Angiotensin-converting enzyme inhibitor promotes coronary collateral circulation
      in patients with coronary artery disease.
AB  - Previous studies have suggested that angiotensin-converting enzyme inhibitors
      (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present
      study was designed to determine the association between treatment with ACEI and
      the development of coronary collateral circulation, as assessed by the Rentrop
      Score, in patients with coronary artery disease (CAD) in a case - control study.
      Subjects included 456 patients with angina who underwent coronary angiography.
      Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels,
      and who received only ACEI without any other anti-hypertensive medication were
      defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56)
      were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the
      cases included a higher percentage of patients with Rentrop Score of at least 1
      than the controls, suggesting that ACEI was associated with coronary collateral
      circulation. Patients with 1-V disease who were treated with ACEI were most
      likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral
      circulation, as assessed by a multiple logistic regression analysis. Therefore,
      treatment with ACEI was associated with the development of collateral circulation
      in patients with CAD, suggesting that such an action is associated with
      bradykinin production by ACEI.

PMID- 12808274
TI  - Early and late results of cardiac and thoracic aortic surgery in octogenarians:
      comparison with high-risk younger patients.
AB  - Forty octogenarians (OCTO) undergoing a variety of cardiac and thoracic aortic
      surgeries using cardiopulmonary bypass (CPB) between 1994 and 2002 were
      retrospectively studied. The results were compared with those of high-risk
      younger patients aged less than 60 years (YOUNG) (n=89). All patients had an
      expected operative mortality of EuroSCORE 5 and over. The EuroSCORE score was
      9.9+/-3.3 (range, 5-18) in the OCTO group and 6.8+/-2.3 (range, 5-16) in the
      YOUNG patients (p<0.0001). There were 4 (10%) and 10 (11%) hospital deaths,
      respectively (p>0.99). Major postoperative complications occurred in 50% of the
      OCTO and 36% of the YOUNG patients (p=0.17). There were 10 and 7 late deaths,
      respectively. Actuarial survival including hospital death was significantly lower
      in the OCTO group than in the YOUNG (p=0.033). Actuarial survival was
      significantly higher in female octogenarians than in male (p=0.046). The overall
      3-year survival rate was 88+/-8% and 64+/-11%, respectively. Multivariate
      analysis showed that predictors of late death were male gender (p=0.0005) and a
      high EuroSCORE (p=0.0010). Cardiac and thoracic aortic surgery using CPB can be
      performed in octogenarians with an acceptable hospital mortality rate and
      gratifying medium-term survival results.

PMID- 12808275
TI  - Beneficial effects of low-dose benidipine in acute autoimmune myocarditis:
      suppressive effects on inflammatory cytokines and inducible nitric oxide
      synthase.
AB  - Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS)
      contributes to the progression of myocardial damage in myocarditis. Some
      dihydropyridine calcium channel blockers reportedly inhibit NO production and
      proinflammatory cytokines and the present study sought to clarify if a low dose
      of benidipine, a novel dihydropyridine calcium channel blocker, would ameliorate
      experimental autoimmune myocarditis (EAM). Rats with or without myocarditis were
      administered oral benidipine at a dose of 3 mg. kg(-1). day(-1) for 3 weeks. Low
      dose benidipine did not decrease blood pressure significantly compared with the
      untreated group, but markedly reduced the severity of myocarditis. Myocardial
      interleukin-1beta (IL-1beta) expression and IL-1beta-positive cells were
      significantly less in rats with EAM that were treated with low-dose benidipine
      compared with untreated rats. Also, myocardial iNOS expression and iNOS-positive
      cells were markedly reduced in in the treated rats compared with the untreated
      group. Furthermore, myocardial NO production and nitrotyrosine expression were
      suppressed by the treatment in rats with EAM. The cardioprotection of low-dose
      benidipine may be caused by suppression of inflammatory cytokines and inhibition
      of NO production.

PMID- 12808276
TI  - Rupture of an aneurysm resulting from a coronary artery fistula: a case report.
AB  - A rare case of coronary-to-pulmonary artery fistulas associated with formation of
      a saccular aneurysm that ruptured into the pericardium occurred in a 69 year-old
      female who had experienced an episode of unconsciousness 3 months earlier and who
      suffered a second episode. She was diagnosed as having a cardiac tamponade caused
      by rupture of a coronary artery aneurysm formed by a left coronary artery -
      pulmonary artery fistula. The hemorrhage stopped after pericardial drainage. She
      was referred for surgical treatment of the aneurysm and suture closure of the
      afferent coronary artery into the aneurysm, transpulmonary closure of the
      fistulas, and aneurysmorrhaphy. There was adhesion between the aneurysm and
      pericardium. Her postoperative course was uneventful and she has remained well
      for 4 months after the operation.

PMID- 12808277
TI  - Highly vascular pelvic tumor causing high-output heart failure because of massive
      arteriovenous shunting: a case report.
AB  - A 53-year-old Japanese woman underwent investigation of her heart murmur. A
      continuous abdominal bruit was heard. Blood gas analysis and chest X-ray showed
      congestive heart failure. Enhanced computed tomography of the pelvis showed a 10
      x 4 cm hypervascular tumor in the retroperitoneal space. Cardiac catheterization
      disclosed a cardiac output of 13.2 L/min and a step-up of oxygen at the right
      common iliac vein. Abdominal aortic angiography showed an extremely vascular
      pelvic tumor and rapid filling of the inferior vena cava. This is a rare case of
      a highly vascular pelvic tumor causing high-output heart failure because of th
      massive arteriovenous shunting.

PMID- 12808278
TI  - Left ventricular apical thrombus formation in a patient with suspected tako-tsubo
      like left ventricular dysfunction.
AB  - A 74-year-old woman with hypertension and bronchial asthma had chest discomfort
      at rest and 4 days later was admitted to her nearby hospital because of the
      sudden onset of right hemiparesis. The hemiparesis had almost disappeared within
      24 h of onset, but because an electrocardiogram showed sinus tachycardia and
      diffuse symmetrical T-wave inversion, she was referred for cardiac examination.
      Coronary angiography did not reveal any significant coronary artery stenosis, but
      left ventriculography revealed severe hypokinesis of the left ventricular apical
      region, which contained a 4 x 4-mm solid thrombus moving freely with a wavy
      motion. Moreover, the activity of both protein C and protein S had decreased. The
      thrombus disappeared after 2 weeks of anticoagulant treatment with warfarin. Her
      clinical course suggested that the transient cerebral ischemic attack was caused
      by embolism of the left ventricular thrombus associated with 'tako-tsubo-like
      left ventricular dysfunction'.

PMID- 12808279
TI  - Sudden death of a case of hypertrophic obstructive cardiomyopathy 19 months after
      successful percutaneous transluminal septal myocardial ablation.
AB  - A 56-year-old male with hypertrophic obstructive cardiomyopathy complicated with
      medically refractory paroxysmal atrial fibrillation and congestive heart failure
      was treated with percutaneous transluminal septal myocardial ablation. The
      resting left ventricular outflow tract gradient decreased from 70 mmHg to 0 mmHg
      after the procedure, and clinical symptoms improved dramatically. However, the
      patient died suddenly 19 months later and autopsy revealed nontransmural
      myocardial fibrosis with an irregular border in the interventricular septum.

PMID- 12808280
TI  - Telemedicine of the heart: real-time telescreening of echocardiography using
      satellite telecommunication.
AB  - The early detection of disease is important to keep people healthy, but it is not
      easy for elderly residents living in rural areas at a distance from well-equipped
      medical institutes to be examined. Therefore, the present study evaluated the
      usefulness of real-time telescreening of echocardiography using satellite
      communications. The participants in this study were 57 residents of a rural
      community in Japan. The resolution of the real-time ultrasound images sent by
      communications satellite was almost identical to that of the original images
      taken in the hospital. Although some problems remain to be solved, telescreening
      of echocardiography will be a practical method for public health in the near
      future.

PMID- 12808281
TI  - Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils
      with a broad apoptosis-inducing activity.
AB  - Calprotectin, a complex of two calcium-binding proteins that belong to the S100
      protein family, is abundant in the cytosolic fraction of neutrophils. A high
      level of calprotectin reportedly exists in extracellular fluid during various
      inflammatory conditions, such as rheumatoid arthritis, cystic fibrosis and
      abscesses. However, the exact biological role(s) of the factor is now under
      investigation. We recently observed that neutrophils contain a factor that shows
      growth-inhibitory and apoptosis-inducing activities against various cell types
      including tumor cells and normal fibroblasts, and we identified that factor as
      calprotectin. The findings suggest that calprotectin exerts a regulatory activity
      in inflammatory processes through its effect on the survival or growth states of
      cells participating in the inflammatory reaction. It is also possible that
      calprotectin, at a high concentration, might have a deleterious effect on
      fibroblasts and influence the recovery of inflammatory tissue. Therefore, the
      protein factor may be a new drug target to control inflammatory reactions. We
      found that a few of the Amaryllidaceae alkaloids effectively inhibited the growth
      inhibitory and apoptosis-inducing activities of calprotectin. In this article, we
      focus on the biological functions of calprotectin in extracellular fluids,
      focusing on its apoptosis-inducing activity.

PMID- 12808282
TI  - Development of enzyme-linked immunosorbent assay for therapeutic drug monitoring
      of mexiletine.
AB  - This paper reports a sensitive and specific enzyme-linked immunosorbent assay for
      determination of the antiarrhythmic drug mexiletine in human serum. Anti
      mexiletine antibody was obtained by immunizing rabbits with an antigen conjugated
      with mercaptosuccinyl bovine serum albumin using N-(epsilon
      maleimidocaproyloxy)succinimide as a heterobifunctional coupling agent. Enzyme
      labeling of mexiletine with beta-D-galactosidase was performed using
      glutaraldehyde. In this assay, the mexiletine to be quantified is chemically
      modified by acetic anhydride allowed to compete with a mexiletine-beta-D
      galactosidase conjugate for binding to a limited amount of an anti-mexiletine
      antibody which was used to coat the wells of a microtiter plate. Mexiletine
      concentrations lower than 80 ng/ml were measurable reproducibly by the enzyme
      linked immunosorbent assay. This assay was specific for mexiletine and showed
      very slight cross-reactivity with its major metabolite, 2-hydroxymethylmexiletine
      (1.5%), but none with p-hydroxymexiletine. The values of serum mexiletine levels
      from 15 patients by this enzyme-linked immunosorbent assay were comparable with
      those measured by HPLC. There was a good correlation between the values
      determined by the two methods. The enzyme-linked immunosorbent assay should be a
      valuable tool in therapeutic drug monitoring and pharmacokinetic studies of
      mexiletine.

PMID- 12808283
TI  - Cholesterol synthesis in mice is suppressed but lipofuscin formation is not
      affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard
      and n-6 fatty acid-enriched oils.
AB  - Hypocholesterolemic activity of dietary polyunsaturated fatty acids is observed
      after relatively short-term but not long-term feedings, and their long-term
      feedings are suspected to accelerate aging through tissue accumulation of lipid
      peroxides and age pigments (lipofuscin). To define the long-term effects of fats
      and oils in more detail, female mice were fed a conventional basal diet
      supplemented with lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed
      oil (Rap), high-alpha-linolenic (n-3) perilla oil (Per), or a mixture of ethyl
      docosahexaenoate and soybean oil (DHA/Soy) from 17 weeks to 71 weeks of age. The
      DHA/Soy and Per groups had decreased serum cholesterol levels compared with the
      Lar and Saf groups, but the difference between the Lar and Saf groups was not
      significant. The 3-hydroxy-3-methyglutary-CoA (HMG-CoA) reductase activity in the
      liver was also significantly lower in the Per and DHA/Soy groups. However, no
      significant difference in lipofuscin contents in the brain and liver was observed
      among the 5 dietary groups, despite significant differences in peroxidizability
      indices of the dietary and/or tissue lipids. These results indicate that n-3
      fatty acid-rich oils are hypocholesterolemic by suppressing hepatic HMG-CoA
      reductase activity compared with animal fats and high-linoleic (n-6) oil, but
      tissue lipofuscin contents are not affected by a long-term feeding of fats and
      oils with different degree of unsaturation in mice.

PMID- 12808284
TI  - Interaction of protein-bound polysaccharide (PSK) with smooth muscle myosin
      regulatory light chain.
AB  - The interaction of a protein-bound polysaccharide (PSK) isolated from
      Basidiomycetes with smooth muscle myosin components was evaluated by limited
      digestion, urea/glycerol gel electrophoresis, affinity chromatography and overlay
      assay using a peptide array. PSK was bound to the regulatory light chain (RLC) of
      myosin, but not to the essential light chain. The binding to PSK was definitely
      observed for unphosphorylated RLC, compared to phosphorylated one. From the amino
      acid sequence of the RLC, 490 peptides were synthesized on a cellulose membrane.
      Overlay assays showed that the PSK-binding on the molecule of RLC were localized
      in the N- and C-terminal basic regions and these sites were conserved in RLC from
      the human smooth muscle and nonmuscle cells.

PMID- 12808285
TI  - The presence of ceramidase activity in liver nuclear membrane.
AB  - This report presents a demonstration of ceramidase activity in the nuclear
      membrane or envelope of mammalian livers. The products of ceramidase reaction
      were identified by means of TLC for released fatty acid and HPLC for sphingosine.
      The ceramidase activity was maximum over a broad neutral to alkaline region
      ranging from pH 7.0 to 8.8. This activity was inhibited by N-oleoylethanolamine
      known as a specific inhibitor for ceramidase and by anandamide to a similar
      extent. The enzymatic study suggests that the nuclear ceramidase has different
      properties from other ceramidase reported previously. As sphingomyelinase, one of
      enzymes involved in the sphingomyelin cycle, are known to be present in the
      nuclear membrane, it is now evident that at least two enzymes involved in the
      sphingomyelin cycle are present in the nuclear membrane.

PMID- 12808286
TI  - Genistein prevents bone resorption diseases by inhibiting bone resorption and
      stimulating bone formation.
AB  - Genistein, a soybean-derived isoflavone, has been shown to suppress osteoclastic
      bone resorption. To clarify the mechanisms underlying this action, we
      investigated the effects of genistein on the differentiation, cytoskeleton and
      function in mice osteoclasts in vitro and bone metabolism in ovariectomized rats.
      STUDY DESIGN: Primary OCs were isolated from 3 week-old mice and induced by
      1,25(OH)(2)D(3). Then OCs were exposed to genistein at various concentration of 0
      M, 10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M, and 10(-5) M. The number of TRAP+
      cells were counted as well as the surface area of bone resorption on bone slice.
      F-actin change was observed by Confocal. In vivo, forty 12 week-old female SD
      rats were randomly assigned to four groups: (1) sham operated (Sham); (2) (OVX);
      (3) ovariectomized and treated with estradiol (OVX-E); (4) ovariectomized and
      received genistein (OVX-G). After 12 weeks, BMD, body weight, serum level of
      alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin (OC), IL-1beta,
      TNFalpha, IL-6 and calcitonin (CT) were evaluated. Femur were sectioned. In
      addition, the serum estradiol, the weight of uteri and histological behavior were
      also examined to indicate the side effect of genistein to the uteri. RESULTS: In
      vitro, the number of TRAP+ cells decreased depending on the concentration of
      genistein as well as the area of bone resorption. F-actin became disorder under
      Confocal. In vivo, after treated with genistein, BMD and the serum level of ALP,
      ACP, osteocalcin increased significantly, while the serum level of IL-1beta and
      TNFalpha decreased. Especially, the increase of ALP and osteocalcin of OVX-G was
      higher than that of OVX-E. Histologically, the pachy-trabecula were observed as
      well as the more mineral deposition lines. Additionally, the uterus weight index
      and the serum estradiol in OVX-G rats were lower significantly than those of OVX
      E. The epithelia of uteri gland in OVX-G appeared cubic while those of OVX-E
      became squamous. CONCLUSIONS: Genistein can prevent bone resorption diseases by
      the promotion of bone formation and the prevention of bone resorption with slight
      side effect.

PMID- 12808287
TI  - Contribution of lipid dynamics on the inhibition of bovine brain synaptosomal Na+
      K+-ATPase activity induced by 4-hydroxy-2-nonenal.
AB  - The effects of lipid hydroperoxide degradation products, such as 4-hydroxy-2
      nonenal (HNE) and malondialdehyde (MDA), on bovine brain synaptosomal ATPase
      activities and their membrane lipid organization were examined. When the
      synaptosomes were treated with HNE, this resulted in the decrease of Na(+)-K(+)
      ATPase activity with the loss of sulfhydryl (SH) groups in the membrane proteins.
      In contrast, MDA treatment of the synaptosomes did not induce an appreciable
      decrease in the ATPase activity or a loss of SH groups. The decreases in ATPase
      activity and SH content by treatment with HNE were also observed, as a Na+-K+
      ATPase preparation was used in place of the synaptosomes. On the other hand, HNE
      had very little effect on synaptosomal Ca2+- and Mg2+-ATPase activities. The
      results of the kinetic analysis of the Na+-K+-ATPase activity indicated that the
      decrease in the activity by HNE-modification is due to a decreased affinity for
      the substrate. ATP completely protected the ATPase from the HNE attack.
      Modification of the synaptosomes with HNE caused a decrease in the membrane lipid
      fluidity near the lipid/water interface, not the lipid layer interior. In
      addition, it was found that there is a good relationship between the lipid
      fluidity and the Na+-K+-ATPase activity under the presence of various
      concentrations of HNE, suggesting that the lipid dynamics are closely related to
      HNE-induced inhibition of the ATPase activity. On the other hand, MDA did not
      induce change in the membrane lipid fluidity. HNE and MDA are mainly incorporated
      into the lipid and protein fractions in the synaptosomal membranes, respectively.
      Based on these results, we proposed a possible mechanism of HNE-induced
      inhibition of synaptosomal Na+-K+-ATPase activity associated with alterations in
      the membrane lipid organization.

PMID- 12808288
TI  - Identification of selenoprotein P fragments as a cell-death inhibitory factor.
AB  - Megakaryoblastoma (Dami cells) cultured in a serum-free medium containing
      albumin, proliferated for three days but died on the fourth day. This cell death
      was not observed when human plasma was added, suggesting that human plasma
      contains a cell-death inhibitory factor. In order to identify this factor, we
      purified it from human plasma. N-terminal amino acid sequence analysis revealed
      that this factor is a mixture of C-terminal fragments of selenoprotein P, a major
      selenocysteine-containing protein in plasma. The specific activity (unit per pmol
      of selenium) of selenoprotein P fragments protein was 15-fold and 1900-fold
      higher than that of the full-length SeP and sodium selenite, respectively.

PMID- 12808289
TI  - Increased expression of Hsp70 for resistance to deuterium oxide in a yeast mutant
      cell line.
AB  - Labeling with stable isotopes, typically deuterium (D), is powerful tool for
      studying the functional structure of biomolecules by NMR. Biosynthesis of certain
      deuterated proteins in microorganisms cultured in deuterium oxide (D(2)O) is an
      attractive strategy. However, the growth of almost all microorganisms is
      inhibited at high concentrations of D(2)O. We isolated a mutant of yeast that
      grows well in D(2)O. The expression of Hsp70 was enhanced in the mutant. The
      increased expression also endowed the yeast with cold-resistance. The mutant
      might be useful for biosynthesis of D-labeled biomolecules.

PMID- 12808290
TI  - Protective effects of quinic acid derivatives on tetrahydropapaveroline-induced
      cell death in C6 glioma cells.
AB  - Protective effects of quinic acids from Aster scaber on tetrahydropapaveroline
      (THP)-induced cell toxicity were evaluated in rat C6 glioma cells. Among 4 quinic
      acid derivatives tested, (-) 4,5-dicaffeoyl quinic acid (QA3) exhibited the
      highest protective effect against THP-induced cell toxicity. C6 cells treated
      with THP exhibited the decrease in the survival rate and activities of
      glutathione peroxidase and catalase, but increased the level of malondialdehyde
      and superoxide dismutase activity. Staining C6 cells with propidium iodide and
      Hoechst 33342 revealed that 10 microM of THP treatment caused to necrotic and
      apoptotic cell death. However, preincubation of cells with QA3 prior to THP
      exposure recovered the cell survival rate and activities of antioxidant enzymes
      to control level. Taken together, the results indicate that QA3 might be a
      potential agent for treating or preventing diseases with oxidative stress.

PMID- 12808291
TI  - Effects of KD3-671, an angiotensin II type 1 receptor antagonist, on anti-thy-1
      nephritis in rats.
AB  - We examined the effects of KD3-671 (2-propyl-8-oxo-1-[(2'-(H-tetrazole-5
      yl)biphenyl-4-yl)methyl]-4,5,6,7-tetrahydrocycloheptimidazole), an angiotensin II
      type1 receptor antagonist, on an experimental rat model of mesangioproliferative
      glomerulonephritis, anti-Thy-1 nephritis. Anti-Thy-1 nephritis was induced by
      intravenous injection of 300 microg/kg of anti-Thy-1.1 monoclonal antibody into
      rats. KD3-671 (3, 10, 30 mg/kg per day) or enalapril (30 mg/kg per day), an
      angiotensin II converting enzyme inhibitor, was given p.o. once daily from the
      day before the antibody injection (the 1st day) to the 15th day after. KD3-671
      significantly inhibited an increase in the number of total and proliferating cell
      nuclear antigen-positive cells and the deposition of alpha-smooth muscle actin
      and fibronectin in the glomeruli of nephritic rats, but enalapril (30 mg/kg per
      day) suppressed only the number of total cells and the deposition of alpha-smooth
      muscle actin in the glomeruli. Moreover, to elucidate the effect of KD3-671 on
      matrix deposition in the glomeruli, we measured the production of fibronectin in
      isolated glomeruli obtained from anti-Thy-1 nephritic rats. The glomeruli in anti
      Thy-1 nephritic rats produced more fibronectin than that in control rats. KD3-671
      (10(-8), 10(-7), 10(-6) M) dose-dependently attenuated fibronectin production in
      isolated nephritic glomeruli. These findings suggest that KD3-671 may be an
      effective agent for the treatment of mesangioproliferative glomerulonephritis.

PMID- 12808292
TI  - Pharmacokinetic study of the digoxin-acenocoumarol interaction in rabbits.
AB  - A study was carried out to evaluate the potential pharmacokinetic interaction
      between digoxin and acenocoumarol. The binding of digoxin to rabbit cardiac
      tissue homogenates was assessed in vitro, using the equilibrium dialysis
      technique. An increase in the first-order constant (p<0.05) and a reduction in
      the partition coefficient in the equilibrium situation (p<0.001) of digoxin were
      observed when the cardiac homogenates were previously treated with acenocoumarol.
      In the in vivo study, the kinetics of digoxin administered in single and multiple
      dosage regimens were compared in control rabbits and in rabbits treated
      simultaneously with acenocoumarol. Kinetic analysis of the results was performed
      using Non-linear Mixed Effects Modeling (NONMEM). In the presence of
      acenocoumarol, the population distribution volume (Vd) of digoxin was increased
      by 40-60%, no differences being found as regards the elimination clearance. Also,
      joint administration of both drugs led to a reduction in digoxin concentrations
      in the heart (p<0.01) at the end of the dosage regimen. Both sets of results
      point to the hypothesis of a hitherto unreported possible pharmacokinetic
      interaction between the two drugs affecting the distribution process. This
      interaction could lead to lower plasma digoxin levels, in view of the increased
      Vd, and a possible reduction in the therapeutic effect, owing to the decrease in
      affinity and in concentration in heart tissue.

PMID- 12808293
TI  - Antioxidative potential of fluvastatin via the inhibition of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase activity.
AB  - We previously reported that fluvastatin, a potent 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, a strong lipid lowering drug, exerted
      an anti-atherosclerotic effect at doses insufficient to lower serum lipids in
      cholesterol fed rabbits. The evidence demonstrated that the superoxide anions
      from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a critical
      role in several steps in the development of atherosclerosis. This study was
      designed to determine the effects of HMG-CoA reductase inhibitors on the
      production of the superoxide anions of NADPH oxidase in isolated rat peritoneal
      neutrophils. Fluvastatin (1-10 microM) decreased phorbol 12-myristate 13-acetate
      (PMA, 10 nM)-dependent reactive oxygen species (ROS) generation in a
      concentration-dependent manner. It also (10 microM) decreased PMA-dependent O(2)
      consumption of the rat neutrophils. These effects were reversed by the addition
      of mevalonate, a metabolite in the HMG-CoA reductase pathway. Treatment with
      pravastatin did not show any significant changes. Fluvastatin (10 microM)
      decreased ROS, such as hydroxyl radicals and superoxide anions generated by the
      Fenton reaction, and by the xanthine-xanthine oxidase system. Rats were treated
      with either fluvastatin (5 mg/kg per day, p.o.) or pravastatin (5 mg/kg per day,
      p.o.) for 1 week. Treatment with fluvastatin decreased the PMA-dependent ROS
      generation. The fluvastatin induced effect on the PMA-dependent ROS generation
      was reversed by the combined administration with 40 mg/kg mevalonate per day. The
      antioxidative effect of fluvastatin was thought to have caused not only the
      scavenging action of the radicals but also to have inhibited ROS generation by
      inhibiting the NADPH oxidase activity. This antioxidative potential of
      fluvastatin via the inhibition of NADPH oxidase activity may be profitable in
      preventing atherosclerosis.

PMID- 12808294
TI  - Oral administration of proteoglycan isolated from Phellinus linteus in the
      prevention and treatment of collagen-induced arthritis in mice.
AB  - To examine whether oral administration of proteoglycan derived from Phellinus
      linteus, which is known as the medicinal mushroom, can prevent or treat collagen
      induced arthritis (CIA) in mice as experimental model of autoimmune disease. CIA
      was induced by intradermal injection of type II collagen (CII) emulsified with
      complete freund's adjuvant (CFA) into the base of the tail (on day 7) followed by
      a booster injection on day 21 into the footpad. To examine the ability of
      proteoglycan to effect the inhibition of CIA, doses of proteoglycan were orally
      administered on day 0 (pre-administration) or day 28 (post-administration) at two
      groups. The inhibition of CIA by oral administration of proteoglycan was
      associated with decrease in anti-CII IgG and IgG2a antibodies (Abs) as well as
      varying kinds of cytokines including IL-12, TNF-alpha, and IFN-gamma. The results
      showed that administration of proteoglycan was followed by decrease of CIA of the
      mice in pre- and post-administration groups. Our findings suggest that
      immunomodulating proteoglycan isolated from P. linteus may be crucially involved
      in the prevention and treatment of autoimmune joint inflammation such as
      rheumatoid arthritis, although no definite role of anti-CII Abs in the human
      disease has been established.

PMID- 12808295
TI  - Subacute toxicity and toxicokinetics of a new antibiotic, DW-224a, after single
      and 4-week repeated oral administration in dogs.
AB  - The subacute toxicity and toxicokinetics of a new fluoroquinolone antibiotic, DW
      224a, were evaluated after single (on the 1st day) and 4-week (on the 28th day)
      oral administration of the drug at doses of 0 (to serve as a control), 10, 30,
      and 90 mg/kg/d, to male and female dogs (n=3 for male and female dogs for each
      dose). During the test period, clinical signs, mortality, body weight, food
      consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross
      findings, organ weight and histopathology were examined. The 4-week repeated oral
      dose of DW-224a resulted in vomiting, salivation, increased serum cholesterol
      level, and atrophy of thymus and testes. The target organ was determined to be
      the thymus and testes. The absolute toxic dose of DW-224a was 30 mg/kg and the
      level at which no adverse effects were observed was 10 mg/kg for both sexes.
      There were no significant gender differences in the pharmacokinetic parameters of
      DW-224a for each dose after both single and 4-week oral administration. The
      pharmacokinetic parameters of DW-224a were dose independent after a single oral
      administration; the time to reach the peak plasma concentration (T(max)) and the
      dose-normalized area under the plasma concentration-time curve from time zero to
      24 h in plasma (AUC(0-24 h)) were not significantly different among the three
      doses. The accumulation of DW-224a after 4-week oral administration was not
      notable at the toxic dose of 90 mg/kg/d. For example, after 4-week
      administration, the dose-normalized AUC(0-24 h) value at 90 mg/kg/d (7.69, 7.05
      microg h/ml) was not significantly greater than that at 10 mg/kg/d. After 4-week
      oral administration, the dose-normalized C(max) and AUC(0-24 h) at 90 mg/kg/d
      were not significantly higher and greater, respectively, than those after a
      single oral administration.

PMID- 12808296
TI  - Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by
      esculetin.
AB  - Linoleic acid hydroperoxide (LOOH) has been reported to cause an increase in the
      content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a typical oxidation
      product of DNA bases, in cultured cells due to coexisting iron(III) ion. We
      examined whether coumarins are able to suppress the formation of 8-oxodG in the
      DNA of human diploid fibroblasts, TIG-7 cells, treated with LOOH and iron(III)
      ion. Cotreatment of TIG-7 cells with esculetin (6,7-dihydroxycoumarin)
      significantly suppressed the increase in 8-oxodG content induced by LOOH and
      iron(III) ion. Pretreatment of cells with esculetin for 24 h was also effective
      in protecting cellular DNA against oxidative damage induced by subsequent
      treatment with LOOH and iron(III) ion. Pretreatment with esculin, the 6-glucoside
      of esculetin, was effective, but to a lesser extent. Furthermore, the free
      radical-scavenging activities of coumarins and hydroxycinnamic acids were
      examined by measuring the inhibition of spin-adduct formation of hydroxyl
      radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Compounds bearing an ortho
      catechol moiety, such as esculetin, fraxetin, and caffeic acid, significantly
      reduced the ESR signal intensities of the DMPO-OH spin adduct. These results
      indicate that esculetin is effective in protecting cells against DNA damage
      induced by oxidative stress and that the presence of an ortho-catechol moiety is
      important for antioxidant activities against reactive oxygen species.

PMID- 12808297
TI  - Isolation and quantitative analysis of cryptotanshinone, an active quinoid
      diterpene formed in callus of Salvia miltiorrhiza BUNGE.
AB  - Effect of N(6)-benzyladenine (BA) on tanshinone formation in callus cultures of
      Salvia miltiorrhiza was examined in an attempt to increase the productivity of
      the medicinal compound, cryptotanshinone. Primary callus was induced by culturing
      leaf explants on Murashige and Skoog's (MS) basal medium supplemented with 1.0 mg
      l(-1) of 2,4-dichlorophenoxyacetic acid (2,4-D) in darkness. The callus
      proliferated further on MS basal medium containing 1.0 mg l(-1) 2,4-D and 0.5 mg
      l(-1) BA and was analyzed for cryptotanshinone by high performance liquid
      chromatography (HPLC). The HPLC results indicated that it contained small amounts
      of cryptotanshinone (0.26+/-0.05 mg/g dry wt). Omission of 2,4-D from the medium
      resulted in a marked increase in the content of cryptotanshinone in callus. The
      HPLC analysis revealed that the content of cryptotanshinone in the callus
      cultured on the MS basal medium supplemented with 0.1, 0.2, 0.5, 1.0, and 2.0 mg
      l(-1) of BA was significantly higher than the marketed crude drug (processed
      underground parts of S. miltiorrhiza). Maximum yield of cryptotanshinone (4.59+/
      0.09 mg/g dry wt) was observed in the callus cultured on MS basal medium
      supplemented with 0.2 mg l(-1) BA for 60 d. Cryptotanshinone was isolated from
      callus through silica gel column chromatography followed by preparative TLC and
      characterized based on NMR and mass spectral data.

PMID- 12808298
TI  - Effect of Radix Ginseng and Radix Trichosanthis on the melanogenesis.
AB  - Melanogenesis is a well known physiological response of human skin exposed to
      ultraviolet light, genetic reasons and other sources. In this study, we conducted
      to evaluate the effects of Radix Ginseng (RG) and Radix Trichosanthis (RT) on the
      melanogenesis in the B16 melanoma cells. The cells were treated for 48 h with RT
      at concentrations ranging from 1 to 50 microg/ml, RG at concentration of 10-1000
      microg/ml, or RG at various doses (10-1000 microg/ml) with 25 microg/ml RT.
      Treatment with RT alone dose-dependently suppressed tyrosinase activity and
      melanin content compared with untreated control, and significantly inhibited cell
      proliferation. However, RG at various concentrations did not exhibit any
      significant change of them. Treatment with RT in the presence of various
      concentrations of RG suppressed tyrosinase activity and melanin content, similar
      to treatment with RT alone, but slightly increased cell proliferation.
      Furthermore, tyrosinase protein level was significantly decreased in treatment
      with 25 microg/ml RT alone and with a combination of 100 microg/ml RG. These
      results indicate that treatment with RG and RT significantly inhibits the
      melanogenesis in B16 cells, and raise the possibility that this combination may
      be effective in the whitening agent for the skin.

PMID- 12808299
TI  - 3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic
      lipase.
AB  - The pancreatic lipase inhibitory activity of the rhizome of Alpinia officinarum
      (AO) and its antihyperlipidemic activity were measured. When the water extract of
      AO was fractionated stepwise with organic solvents, the ethyl acetate fraction
      exhibited the most potent inhibition. 3-Methylethergalangin was isolated from
      that fraction as an inhibitor of pancreatic lipase with an IC(50) value of 1.3
      mg/ml (triolein as a substrate). AO and its ethyl acetate fraction significantly
      inhibited the serum TG level in corn oil feeding-induced triglyceridemic mice,
      and serum triglyceride (TG) and cholesterol in Triton WR-1339-induced
      hyperlipidemic mice. However, this compound and the AO ethyl acetate fraction did
      not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic
      mice. The results suggest that the hypolipidemic activity of AO and 3
      methylethergalangin is due to the inhibition of pancreatic lipase.

PMID- 12808300
TI  - Effect of ginsenosides administered intrathecally on the antinociception induced
      by cold water swimming stress in the mouse.
AB  - We examined the effects of ginseng total saponin (GTS) and several ginsenosides
      injected intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on the
      antinociception induced by cold water swimming. The tail-flick response was used
      as an antinociceptive parameter. We found that i.t. injection of GTS time- and
      dose-dependently attenuated inhibition of the tail-flick response induced by cold
      water swimming, although GTS given i.c.v. had no significant effect on the
      latency of the tail-flick response induced by cold water swimming. To identify
      those responsible for antagonism of GTS against cold water swimming-induced
      antinociception, the effects of various kinds of ginsenosides (R(b1), R(b2),
      R(c), R(d), R(e), and R(g1)) on inhibition of the tail-flick response induced by
      cold water swimming were examined. R(b1), R(d), R(e), and R(g1) effectively
      attenuated the inhibition of the tail-flick response induced by cold water
      swimming stress. Our results suggest that GTS injected spinally, but not
      supraspinally, reduces the antinociception induced by this stress, and that the
      responsible ginsenosides against antinociception induced by cold water swimming
      may be R(b1), R(d), R(e), and R(g1). Moreover, the possible involvement of the
      opioid system in the regulation of cold water swimming stress-induced
      antinociception by these four ginsenosides is discussed.

PMID- 12808301
TI  - A quantitative ELISA using monoclonal antibody to survey paeoniflorin and
      albiflorin in crude drugs and traditional Chinese herbal medicines.
AB  - This work describes an immunochemical approach for the quality control of
      Paeoniae Radix by an enzyme-linked immunosorbent assay (ELISA) based on
      determination of the total concentration of paeoniflorin (PF) and albiflorin
      (Alb), which are major bioactive constituents in Paeoniae Radix. Four hybridromas
      secreting monoclonal antibodies against PF and Alb were produced by fusing
      splenocytes from a mouse immunized by a PF-bovine serum albumin (BSA) conjugate
      with the hypoxanthine-aminopterin-thymidine (HAT)-sensitive mouse myeloma cell
      line, P3-X63-Ag8-653. A relatively higher reactivity of monoclonal antibodies
      (MAbs) with PF and Alb than oxypaeoniflorin (OP) and benzoylpaeoniflorin (BP) was
      observed, while other monoterpenes and benzoic acid did not cross-react. When PF
      was used as a standard, the assay can cover a measuring range of 20-600 ng/ml for
      PF and Alb. A series of Paeoniae Radix samples have been determined, and the
      results showed good agreement with that determined by traditional high
      performance liquid chromatography (HPLC). The developed competitive ELISA was 100
      times more sensitive than the HPLC method. Meanwhile, fifteen Chinese traditional
      prescriptions were determined by the competitive ELISA.

PMID- 12808302
TI  - Field survey of Glycyrrhiza plants in Central Asia (1). Characterization of G.
      uralensis, G. glabra and the putative intermediate collected in Kazakhstan.
AB  - The characteristics of Glycyrrhiza plants from 12 collection sites in
      southeastern Kazakhstan were investigated. G. uralensis was observed at 9 of the
      sites from Almaty to Shu, and G. glabra was observed at 8 sites. At 4 sites near
      Shu, and 1 site near Almaty, G. glabra and G. uralensis grew together forming a
      mixed population, and intermediate-type plants between them were also observed at
      3 sites. Although two nucleotide substitutions of the chloroplast rbcL gene were
      observed between G. uralensis and G. glabra, rbcL sequences of the intermediate
      types were divided into G. uralensis-type (G-A type) and G. glabra-type (A-T
      type). HPLC analysis of the roots indicated that species-specific flavonoids,
      glabridin and glycycoumarin, were detected in the roots of G. glabra and G.
      uralensis, respectively, but neither flavonoid was detected in underground parts
      of the intermediate-types. HPLC analysis of their leaves indicated a significant
      difference among G. uralensis, G. glabra and the intermediate-type plants. Both
      G. glabra-specific and G. uralensis-specific compounds were detected in the
      leaves of the intermediate-type, thus suggesting that the intermediate plants are
      hybrids of G. glabra and G. uralensis.

PMID- 12808303
TI  - Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients
      with renal failure on haemodialysis.
AB  - Objective of the present study was to investigate the elimination kinetics of
      quinaprilat and perindoprilat, the active metabolites of angiotensin-converting
      enzyme (ACE) inhibitors quinapril and perindopril, in hypertensive patients with
      renal failure under haemodialysis to evaluate the appropriate duration of off
      dose of these drugs before starting of low-density lipoprotein (LDL) apheresis.
      The informed consent was received from 12 hypertensive patients with renal
      failure, who were under haemodialysis (42 to 62 years). The patients received
      oral administration of quinapril (10 mg) or perindopril (2 mg) once a day for
      four weeks. First, to evaluate the dialyzability of each metabolite, blood
      samples were collected before and after haemodialysis one week after the repeated
      doses. Second, to evaluate the elimination kinetics of quinaprilat or
      perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after
      the final administration. Plasma concentrations of quinaprilat and perindoprilat
      were measured by high-performance liquid chromatography (HPLC) and
      radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a
      model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction
      ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for quinaprilat and 108.1+/
      5.9 ml/min and 0.75+/-0.04 for perindoprilat, respectively. The terminal
      elimination half-lives of quinaprilat and perindoprilat were 60.7+/-2.1 and
      79.9+/-14.0 h, respectively. The dialyzability of perindoprilat was much higher
      than that of quinaprilat probably due to low protein binding potency. The present
      study suggests that hypertensive patients receiving chronic therapy with
      quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3
      weeks before LDL apheresis.

PMID- 12808304
TI  - Clinical efficacy of therapeutic drug monitoring in patients receiving
      vancomycin.
AB  - Efficacy of therapeutic drug monitoring (TDM) of vancomycin (VCM) was
      retrospectively investigated in 184 patients with methicillin-resistant
      Staphylococcus aureus (MRSA) infection. The incidence of nephrotoxicity was
      compared between the patients who received TDM practice (TDM group, n=73) and did
      not (non-TDM group, n=111). Creatinine clearance (CLcr) values decreased
      significantly after the VCM therapy in the non-TDM group (p<0.05). The patients
      with MRSA bacteremia or pneumonia were classified into two groups according to
      peak concentrations of VCM: above 25 microg/ml (Group A: n=29) and below (Group
      B: n=24). Mean duration of VCM therapy (14.1 d) in Group A was significantly
      shorter than that (27.0 d) in Group B. Mean cumulative total VCM doses (13.3 g)
      in Group A was significantly less than that (25.0 g) in Group B. These results
      indicate that monitoring peak concentration is essential to obtain better
      clinical effects for VCM therapy, and that the peak concentration above 25
      microg/ml is more effective.

PMID- 12808305
TI  - Culture time-dependent gene expression in isolated primary cultured rat
      hepatocytes by transfection with the cationic liposomal vector TFL-3.
AB  - The development of a carrier system that enables the transfer of a functional
      exogenous gene to non- or less frequently dividing mammalian cells is essential
      for increasing the available options for the treatment of various diseases. The
      issue of whether TFL-3, a recently developed cationic liposome, can be
      successfully used to achieve gene expression in primary cultured rat hepatocytes
      was examined. The hepatocytes were transfected for 4 h with plasmid DNA (pDNA) in
      TFL-3 at various time points after 4-h preculture. The transfection efficiency
      was determined at various times posttransfection with pDNA coding for
      chloramphenicol acetyltransferase (CAT), luciferase, or beta-galactosidase. The
      amount of intranuclear pDNA present, as a consequence of the lipofection, was
      also quantitatively determined. Successful lipofections were observed for all
      pDNA tested, and the efficiencies were superior to that of commercially available
      LIPOFECTAMINE under our experimental conditions. The degree and rate of gene
      expression were dependent on incubation time prior to lipofection as well as on
      the density of the cells per dish, but this relationship did not hold for the
      amount of gene delivered to the nuclei. These results indicate that TFL-3 could
      be a useful vector for achieving sufficient gene expression in rat hepatocytes
      and suggest that the culture time prior to and following lipofection, which is
      related to the biological condition of the cells, may be one major factor
      affecting efficient gene expression in nondividing cells.

PMID- 12808306
TI  - Factors affecting the microclimate pH of the rat jejunum in ringer bicarbonate
      buffer.
AB  - General characteristics of the microclimate layer on the mucosal surface of the
      rat jejunum incubated in bicarbonate buffers were investigated in vitro using pH
      sensitive flat membrane microelectrode. Jejunal surface microclimate (JSM) pH
      changed from 7.30+/-0.03 to 5.83+/-0.04 when the incubation buffer pH decreased
      from 8.03+/-0.02 to 6.12+/-0.01. Treatment of the mucosal side with mucolytic
      substances L-cysteine (1% (wt/v)) and 1,4-dithio-DL-threitol (2 mM) significantly
      (p<0.01) increased JSM pH. Respiratory chain inhibitor, sodium azide (10 mM) also
      significantly (p<0.05) increased JSM pH. D-Glucose (10 mM) at the mucosal side
      markedly (p<0.05) decreased JSM pH, which was attenuated by Na(+)/H(+) exchange
      inhibitor, amiloride (1 mM). Amiloride had no effect on JSM pH when D-glucose was
      not present at the mucosal side. In contrast to previous observations using
      bicarbonate free incubation buffers, we have demonstrated that JSM pH is not a
      constant value, but is dependent on pH of the incubation buffer. Additionally,
      Na(+)/H(+) exchanger does not contribute to acidic properties of JSM, when there
      is no D-glucose in the bicarbonate incubation buffer at the mucosal side of the
      tissue. In conclusion, we suggest that the bicarbonate buffers which are more
      close to in vivo situation than bicarbonate free buffers should be preferable
      incubation media when examining JSM.

PMID- 12808307
TI  - Kinetic analysis of reversible inhibition of 16alpha-hydroxyandrostenedione
      aromatization in human placental microsomes by suicide substrates of
      androstenedione aromatization.
AB  - To gain insight into the catalytic function of aromatase and its substrate
      specificity, we studied reversible inhibition of 16alpha-hydroxyandrostenedione
      (16alpha-OHAD) aromatization in human placental microsomes by several suicide
      substrates of androstenedione (AD) aromatization, including 4-hydroxyAD (1), 6
      oxoAD (2) and its 19-hydroxy analogue 3, androst-5-ene-4,7,17-trione (4), and
      10beta-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a
      suicide inactivation of 16alpha-OHAD aromatization. All inhibitors examined
      blocked 16alpha-OHAD aromatization in a competitive manner with apparent K(i)
      values ranging from 0.50 to 980 nM. The relative K(i) values between inhibitors 1
      5 obtained in the 16alpha-OHAD aromatization experiments were markedly different
      from those obtained in the AD aromatization experiments. The results predict that
      all inhibitors examined bind to the 16alpha-OHAD binding site in a manner that
      does not cause suicide inactivation of 16alpha-OHAD aromatization. These findings
      would be useful for understanding the active (binding) site structure as well as
      the catalytic function of aromatase.

PMID- 12808308
TI  - Cardiotoxicity of trastuzumab (herceptin) in chick embryos.
AB  - The cardiac toxicity of trastuzumab was studied in chick embryos. Fertilized eggs
      of White Leghorns were incubated and investigated. Trastuzumab 5 mg/egg (low
      dose) or 15 mg/egg (high dose) was injected into the air sac of a fertilized egg
      on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60
      min after the injection. After low dosing of trastuzumab, the heart rate was not
      different compared with the control. However, the heart rate was significantly
      decreased by high dosing of trastuzumab. In addition, arrhythmia was produced by
      high dosing of trastuzumab. These findings indicate that trastuzumab has a marked
      dose- and time-dependent influence on the heart rate in chick embryos.

PMID- 12808309
TI  - Inhibitory effect of the repeated treatment with Unsei-in on substance P-induced
      itch-associated responses through the downregulation of the expression of NK(1)
      tachykinin receptor in mice.
AB  - Unsei-in, a traditional medicine, is prescribed against pruritic cutaneous
      diseases, but the mechanisms of antipruritic action are still unknown. In the
      present study, we examined the antipruritic effects of Unsei-in in mice. Single
      administration of Unsei-in did not inhibit substance P-induced itch-associated
      response (scratching) in mice. However, repeated treatment with Unsei-in for 7 d
      significantly inhibited substance P-induced scratching. The same repeated
      treatment with Unsei-in suppressed the expression of NK(1) tachykinin receptors
      in the skin. These results suggest that Unsei-in inhibits substance P-associated
      itching and that the inhibition is at least partly due to the suppression of the
      expression of NK(1) tachykinin receptors in the skin.

PMID- 12808310
TI  - Kinetic characterization of carrier-mediated transport systems for D-glucose and
      taurocholate in the everted sacs of the rat colon.
AB  - The present study was aimed at kinetically characterizing the carrier-mediated
      transport systems for D-glucose and taurocholate in the rat colon, compared with
      their respective counterparts in the small intestine. The transport of these
      compounds was evaluated by measuring the initial uptake into everted intestinal
      tissue sacs. The uptake of both D-glucose and taurocholate was highly saturable,
      conforming to Michaelis-Menten kinetics without an appreciable nonsaturable
      transport component. The Michaelis constant (K(m)) was 0.43 and 0.021 mM,
      respectively, for D-glucose and taurocholate and the maximum transport rate
      (J(max)) was 0.82 and 0.056 nmol/min/100 mg wet tissue weight (wtw),
      respectively. For both compounds, these values of K(m) and J(max) in the colon
      were one to three orders of magnitude smaller than those in the small intestine,
      suggesting that the transport systems in the colon have by far a higher affinity
      and a lower transport capacity than their counterparts in the small intestine.
      However, it is now evident from kinetic studies that carrier-mediated transport
      systems for D-glucose and taurocholate are also present in the colon. It will be
      interesting to explore the possibility that they could be used for oral drug
      delivery via the colon. Their physiological roles would also be of interest.

PMID- 12808311
TI  - Comparative study of protective effects of chitin, chitosan, and N-acetyl
      chitohexaose against Pseudomonas aeruginosa and Listeria monocytogenes infections
      in mice.
AB  - We conducted a comparative study of the protective effects of chitin, chitosan,
      and N-acetyl chitohexaose (NACOS-6) against mice infected intravenously or
      intraperitoneally with Pseudomonas aeruginosa and Listeria monocytogenes. Mice
      pretreated with chitin, chitosan, and NACOS-6 showed resistance to
      intraperitoneal infections by both microbes. Only mice pretreated with chitin and
      chitosan showed resistance to intravenous infections by both microbes. The
      number, active oxygen generation, and myeloperoxidase activity of peritoneal
      exudate cells (PEC) in the chitin, chitosan, and NACOS-6-treated mice were
      greater than those of the untreated mice. Also, these PEC factors from mice
      pretreated with chitin and chitosan were greater than those from the NACOS-6
      treated mice.

PMID- 12808312
TI  - Effect of the isocoumarin paepalantine on the luminol and lucigenin amplified
      chemiluminescence of rat neutrophils.
AB  - Paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naphto(2,3c)pyran-1-one), a natural
      isocoumarin isolated from the capitula of Paepalanthus bromelioides
      (Eriocaulaceae), was assessed for its effect on the respiratory burst (zymosan
      stimulated luminol-enhanced chemiluminescence and PMA-stimulated lucigenin
      enhanced chemiluminescence) of polymorphonuclear neutrophils in vitro. Special
      attention was devoted to establishing the IC(50) for neutrophils. Paepalantine
      was able to decrease luminol and lucigenin chemiluminescence, reflecting an
      inhibitory effect on the respiratory burst, with an ED(50) of 0.44+/-0.05 and
      0.84+/-0.15 microg/ml, respectively. A cell-free system was performed with
      paepalantine on myeloperoxidase/H(2)O(2) and myeloperoxidase/H(2)O(2)/Cl(-)
      systems. Paepalantine inhibited luminol oxidation in both systems. This
      inhibition was related to the interaction of paepalantine-myeloperoxidase and its
      scavenger effect on HOCl.

PMID- 12808313
TI  - Trypsinogen hL is not a new member of the human trypsinogen family, but a known
      mouse ortholog.
AB  - An allegedly novel human trypsinogen cDNA clone termed trypsinogen hL was
      recently reported in the Biological & Pharmaceutical Bulletin (2003; 26: 361
      364). This "new" trypsinogen sequence was isolated by PCR using human lung cDNAs
      as template and was presumed to be a new member of the human trypsinogen family.
      However, trypsinogen hL does not match any sequence in the human genome; whereas
      it is 100% identical to mouse trypsinogen 7. Thus, trypsinogen hL is not of human
      origin, and its cloning from a human cDNA library was clearly a result of
      contamination with mouse genetic material. Publication of this cloning artifact
      could have been avoided by a simple BLAST search of GenBank or other sequence
      databanks.

PMID- 12808314
TI  - RNA interference in functional genomics and medicine.
AB  - RNA interference (RNAi) is the sequence-specific gene silencing induced by double
      stranded RNA (dsRNA). Being a highly specific and efficient knockdown technique,
      RNAi not only provides a powerful tool for functional genomics but also holds a
      promise for gene therapy. The key player in RNAi is small RNA (approximately 22
      nt) termed siRNA. Small RNAs are involved not only in RNAi but also in basic
      cellular processes, such as developmental control and heterochromatin formation.
      The interesting biology as well as the remarkable technical value has been
      drawing widespread attention to this exciting new field.

PMID- 12808315
TI  - Efficacy of vancomycin-beta-lactam combinations against heterogeneously
      vancomycin-resistant Staphylococcus aureus (hetero-VRSA).
AB  - There have been conflicting data about the interactions between vancomycin and
      beta-lactam agents against Staphylococcus aureus strains with heterogeneous
      resistance to vancomycin. We evaluated the efficacy of these combinations against
      Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains
      which were isolated from Korean patients using a population analysis method.
      Antagonistic effects were observed when less than 1 g/mL of beta-lactam
      antibiotics was combined with vancomycin, whereas synergistic effects were
      noticed with more than 4 microgram/mL of beta-lactam antibiotics. The
      antagonistic effects at low concentrations of beta-lactams were most prominent at
      2 microgram/mL of vancomycin, which were the vancomycin MICs of tested hetero
      VRSA strains. This study showed the variable effects of vancomycin- beta-lactam
      combinations depending on the concentrations of beta-lactam antibiotics and this
      property could be used to develop screening methods for hetero-VRSA strains.

PMID- 12808316
TI  - A virulent strain of Salmonella enterica serovar London isolated in infants with
      enteritis traced by active surveillance and molecular epidemiological study.
AB  - A total of 74 isolates of Salmonella enterica serovar London were collected
      through the Laboratory-Based Diarrheal Diseases Surveillance in 2000-2001. In
      order to characterize the isolates and investigate the source of the epidemic, we
      performed antimicrobial susceptibility tests and XbaI Pulsed-field gel
      electrophoresis (PFGE) of 44 Salmonella London isolates. Forty isolates were from
      feces of infants and four isolates were from adults aged 30, 52, 54, and 59 yr.
      Two subtypes were identified: a tetracycline-susceptible A 0 PFGE pattern and a
      tetracyclineresistant A 1 PFGE pattern. Interestingly, the isolates from all
      infants and one 30-yr-old adult were A 0 PFGE pattern and tetracycline
      susceptible. Furthermore, the A 0 PFGE pattern strain was approximately 2 times
      more virulent than the A 1 PFGE pattern strain, according to the results of in
      vitro invasion assay using J774A.1 macrophage-like cells. These results indicate
      that the active surveillance with molecular epidemiological tools would be
      valuable for promptly finding new epidemic strains. Our results also suggested
      that the virulent Salmonella London strain might infect the infants through a
      common contaminated source.

PMID- 12808317
TI  - Rubella seroprevalence in Korean children.
AB  - The aim of this study was to determine the age-specific rubella seroprevalence
      and the related factors in Korean children. Subjects of the study were 5393
      students from 8 elementary schools in Gyeonggi Province, Korea. Questionnaire
      surveys with blood sampling were conducted in 1993, 1996, and 1999. ELISA tests,
      used to detect rubella specific IgG antibody, were Imx (R) (Abbott, U.S.A.) in
      1993 and 1999, and Enzygnost (Behring, Germany) in 1996. The age-adjusted rubella
      susceptibility rate was 22.9% (95% CI: 22.8-23.0%) and it increased with age from
      14% to 28%. The susceptibility rates of vaccinees, nonvaccinees, and the unknown
      group were 21%, 35%, and 27%, respectively (p=0.000). The rates by parental
      education levels for elementary and below, middle school, high school, and
      college and over were 37%, 26%, 24%, and 20%, respectively. The geometric mean
      titers (GMTs) of nonvaccinees, the unknown group, and vaccinees were 47 IU/mL, 42
      IU/mL, and 37 IU/mL, respectively (p=0.000). The susceptibility level was too
      high to prevent the rubella epidemic in Korea, which necessitates a programme
      that will enhance the coverage for 1st and 2nd MMR vaccination among school
      children. In particular, more attention should be paid to the vaccination of the
      children whose parental education level is relatively low.

PMID- 12808318
TI  - Infarct size-limiting effect of calcium preconditioning in rabbit hearts.
AB  - Recent studies demonstrated that brief period of Ca2+ depletion and repletion
      (Ca2+ preconditioning, CPC) has strong protective effects against ischemia in a
      rat heart. CPC and classic preconditioning (IPC) were compared in relation with
      infarct size and protein kinase C (PKC) isozymes. Isolated Langendorff-perfused
      rabbit hearts were subjected to 45-min ischemia (Isc) followed by 120-min
      reperfusion (R) with or without IPC, induced by 5-min Isc and 10-min R. In the
      CPC hearts, 5-min Ca2+ depletion and 10-min repletion (CPC) were given before 45
      min Isc, with or without concurrent PKC inhibition (calphostin C, 200 nmol/L).
      IPC enhanced recovery of LV function, while CPC did not. Infarct size was
      significantly reduced by both CPC and IPC (p < 0.05 vs. ischemic control).
      Membrane PKC was significantly increased from 2.53 +/- 0.07 (baseline, nmol/g
      tissue) to 3.11+/-0.07, 3.34 +/- 0.11, 3.15 +/- 0.09, and 3.06 +/- 0.08 by IPC,
      IPC and 45-min Isc, CPC and 45-min Isc, respectively (p < 0.01). Immunoblots of
      membrane PKC were increased by IPC, IPC and 45-min Isc, and CPC. These effects
      were abolished by PKC inhibition. Thus, activation of PKC may have trigger role
      in the mechanism of cardioprotective effect by CPC.

PMID- 12808319
TI  - Comparison of clinical and echocardiographic outcomes after valve repair:
      degenerative versus rheumatic mitral regurgitation.
AB  - We compared clinical (30+/-24 months) and echocardiographic follow-up (22 +/- 20
      months) data of 184 consecutive patients with myxomatous degenerative mitral
      regurgitation (Group A) and 85 consecutive patients with rheumatic mitral
      regurgitation (Group B) after repair. Selection criteria for rheumatic etiology
      was predominant mitral regurgitation with valve area >or= 2.0 cm(2) and with no
      significant calcification in valvular apparatus. Repair was successful in 93% of
      group A and in 92% of group B (p>0.05). There was no difference of operative
      mortality (1% vs 0%) and of the incidence of the second-pump valve replacement
      (4% vs 5%). The 4-yr survival, 4-yr event-free survival, and 4-yr mitral
      regurgitation-free survival rates in group A were 96 +/- 2%, 89 +/- 4%, and 76 +/
      5%, respectively, which were not different from those in group B (97 +/-2 %, 93
      +/- 4%, and 68 +/-7 %, p >0.05). Independent determinants of development of at
      least moderate regurgitation in group A were no use of ring annuloplasty (hazards
      ratio 6.6, 95% CI 2.0 to 21.5) and new chordae formation (hazards ratio 3.5, 95%
      CI 1.4 to 8.7). In group B, no use of ring annuloplasty (hazards ratio 15.3, 95%
      CI 3.5 to 66.7) also was independent predictor. Valve repair is highly feasible
      in selected patients with rheumatic mitral regurgitation, and clinical course is
      not significantly different from that of patients with degenerative mitral
      regurgitation.

PMID- 12808320
TI  - A practical protocol for titrating "optimal" PEEP in acute lung injury:
      recruitment maneuver and PEEP decrement.
AB  - This study was conducted to evaluate the effectiveness and safety of a practical
      protocol for titrating positive end-expiratory pressure (PEEP) involving
      recruitment maneuver (RM) and decremental PEEP. Seventeen consecutive patients
      with acute lung injury who underwent PEEP titration were included in the
      analysis. After baseline ventilation, RM (continuous positive airway pressure, 35
      cm H2O for 45 sec) was performed and PEEP was increased to 20 cmH2O or the
      highest PEEP guaranteeing the minimal tidal volume of 5 mL/kg. Then PEEP was
      decreased every 20 min in 2 cmH2O decrements. The "optimal" PEEP was defined as
      the lowest PEEP attainable without causing a significant drop (>10%) in PaO2. The
      "optimal PEEP" was 14.5 +/- 3.8 cmH2O. PaO2 /FI O2 ratio was 154.8 +/- 63.3 mmHg
      at baseline and improved to 290.0 +/- 96.4 mmHg at highest PEEP and 302.7 +/-
      94.2 mmHg at "optimal PEEP", both significantly higher than baseline (p<0.05).
      Static compliance was significantly higher at "optimal" PEEP (27.2 +/- 10.4 mL/
      cmH2O) compared to highest PEEP (22.3 +/- 7.7 mL/cmH2O) (p<0.05). Three patients
      experienced transient hypotension and one patient experienced atrial premature
      contractions. No patient had gross barotrauma. PEEP titration protocol involving
      RM and PEEP decrement was effective in improving oxygenation and was generally
      well-tolerated.

PMID- 12808321
TI  - Pararenal leiomyosarcoma of the inferior vena cava.
AB  - A complete surgical resection is the only proven therapeutic modality that
      prolongs the survival in patients with leiomyosarcoma of the inferior vena cava
      (IVC). Reconstruction of the IVC is not always necessary but is often required to
      facilitate venous drainage of the kidney for the tumors at the pararenal area of
      the IVC. Controversy exists in postoperative adjuvant therapy. Recently, we
      experienced four cases of pararenal leiomyosarcoma of the IVC, of which treatment
      consisted of a complete resection of the tumor, ringed polytetrafluoroethylene
      (PTFE) graft interposition, and bilateral renal vein reconstructions in all
      patients. Postoperative radiation therapy was instituted in 3 of 4 patients. One
      patient who did not receive the postoperative radiation therapy was treated with
      adjuvant chemotherapy. The kidneys were preserved in all patients and no deep
      vein thrombosis (DVT) or venous insufficiency of the lower extremity veins
      developed. Distant metastasis to the lung was noted in one patient at 18 months
      after surgery, who was not received the postoperative radiation therapy but
      chemotherapy. In conclusion, a complete resection of the tumor, IVC
      reconstruction, and bilateral renal vein reconstruction followed by adjuvant
      radiation therapy is recommended for the treatment of pararenal leiomyosarcoma of
      the IVC.

PMID- 12808322
TI  - Surgical treatment for pectus excavatum.
AB  - The aim of this study was to compare clinical outcomes in pectus excavatum
      patients undergoing a Ravitch operation with those undergoing a Nuss procedure.
      Retrospective study was conducted on one hundred and twenty three patients who
      underwent Ravitch operation (n=16) and Nuss procedure (n=107) between 1995 and
      2002. Mean age of the patients was 7.9+/-6.2 yr. In the Ravitch group, operation
      time was 196.9+/-61.0 min, and required 10.2+/-2.6 chondral bone resections.
      Average hospital stay time was 15.9 days. In the Nuss group, operation time was
      67.2+/-33.1 min, and bar removal was required two years after the bar insertion.
      The length of hospital stay was averagely 8.0 days, and postoperative
      reoperations were performed in five patients due to bar displacements, while
      early bar removal was required in one patient. The patient interviews for
      operation results were conducted and revealed that 92.3% of the patients in the
      Ravitch group showed good to excellent, while 93.3% of Nuss bar removed patients
      replied good to excellent. Though Nuss procedure has many advantages, it also has
      some disadvantages. So, the method of the operation should be selected according
      to the characteristics of the patient.

PMID- 12808323
TI  - The treatment of severe aplastic anemia: outcomes of bone marrow transplantation
      and immunosuppressive therapy in a single institution of Korea.
AB  - The present study represents an analysis of 96 patients with severe aplastic
      anemia (SAA) treated in Seoul National University Hospital, Seoul, Korea between
      1990 and 1999. Twenty-two patients were treated by allogeneic bone marrow
      transplantation (BMT) from HLA identical sibling donors and 74 by
      immunosuppressive therapy (IS) with antithymocyte globulin (ATG) or
      antilymphocyte globulin (ALG). There was no statistical difference between the
      two treatment groups in age, sex, disease duration, and previous transfusion
      amount. In the BMT group, grade II-IV acute graft versus host disease (GVHD)
      developed in 10% and chronic GVHD occurred in 33% of patient. Only one patient
      died from complication of transplantation (veno-occlusive disease). Of 74
      patients who received IS treatment, 45% achieved a complete or partial response.
      Twenty patients died among IS treatment group. Major causes of death were
      hemorrhage (40%) and infection (55%). In the BMT group, the 5-yr overall survival
      (OS) was 95% after a median follow-up of 42 months. In the IS group, the 5-yr OS
      was 70% after a median follow-up of 49 months (p=0.04). In conclusion, the long
      term survival rates of SAA in Koreans receiving BMT or IS were excellent compared
      with the Western data. Further evaluation on the prognosis of aplastic anemia in
      Asians should be done.

PMID- 12808324
TI  - Active immunization using dendritic cells mixed with tumor cells inhibits the
      growth of lymphomas.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells for the induction and
      activation of cytotoxic T lymphocytes. We tested whether bone marrow-derived DCs
      are capable of inducing protective immunity against a murine lymphoma (A20). DCs
      were grown from tumor-bearing BALB/c mice by culturing bone marrow cells. BALB/c
      mice were injected (sc) with A20 cells on day 0. Intraperitoneal immunization
      with DCs mixed with lethally irradiated A20 cells were started when the tumor
      reached ca. 4-5 mm in diameter (Group A) or on day -7 (Group B). Booster
      immunizations were given every 3-4 days for four weeks. By 31 days in group A,
      there was a significant reduction in tumor growth in the mice immunized with DCs
      mixed with irradiated A20 cells as compared with the control groups (p=0.016). In
      group B, tumor growth was completely inhibited and there was no tumor growth
      following extended observations after completion of immunization. Thus, DCs mixed
      with irradiated tumor cells can induce an antitumor effect. This provides a
      rationale for the use of DCs mixed with irradiated tumor cells in immunotherapy
      for minimal residual disease of lymphomas.

PMID- 12808325
TI  - Production and expression of Gro-alpha and RANTES by peripheral blood mononuclear
      cells isolated from patients with Kawasaki disease and measles.
AB  - We investigated whether the production and gene expression of Gro-alpha and
      RANTES in Kawasaki disease differ in measles. Forty-two samples from 14 patients
      in different clinical stages of Kawasaki disease, eight samples from 8 patients
      in the acute stage of measles and seven samples from 7 healthy children were
      collected. The present study was performed using ELISA and RT-PCR for the
      productions and gene expression of the chemokines. The production of Gro-alpha
      was markedly elevated during the acute stage of measles compared with Kawasaki
      disease. Moreover, the expression of Gro-alpha was increased in every case of
      measles, but not in Kawasaki disease. The production of RANTES was elevated in
      the acute stage of both diseases when compared to the healthy control. However,
      the plasma RANTES level did not change significantly according to the clinical
      stages of Kawasaki disease. A correlation between the production and gene
      expression of RANTES and Gro-alpha was not found in Kawasaki disease. These
      results suggest that Kawasaki disease differs from measles with regard to Gro
      alpha production and expression, but not RANTES. Gro-alpha might play an
      important role in the acute stage of measles, however not in Kawasaki disease.
      Further studies are needed to clarify the efficacy of Gro-alpha as a marker in
      measles.

PMID- 12808326
TI  - Characterization of mutator pathway in younger-age-onset colorectal
      adenocarcinomas.
AB  - The high-frequency microsatellite instability (MSI-H) phenotype, frequently
      identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts
      for approximately 15% of sporadic colorectal cancers. Microsatellite instability
      (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes,
      i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1
      in sporadic colorectal tumors. The mutator pathway including microsatellite
      instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns
      were identified in 21 sporadic colorectal adenocarcinoma patients younger than 30
      yr excluding HNPCC. More than half of tumors showed MSI, with five MSI-H and six
      MSI-L (low-frequency microsatellite instability). Three of six MSI-H tumors
      showed the hMLH1 promoter methylation and did not express the hMLH1 protein. On
      the other hand, all MSI-L and all MSS (microsatellite stable) tumors expressed
      both hMSH2 and hMLH1 proteins. Two novel mutations, i.e. a missense mutation in
      hMLH1 and a splice-site alteration in hMSH2, were identified in two patients
      respectively. Although mutator pathway was implicated in younger-age-onset
      colorectal carcinogenesis, many tumors appeared to evolve from different genetic
      events other than hMSH2 and hMLH1 mutations frequently identified in HNPCC.

PMID- 12808327
TI  - The pattern of differentially expressed genes in biliary atresia.
AB  - Biliary atresia is a progressive obliterative cholangiopathy, but the etiology of
      this disorder remains uncertain. Identifying genes specifically expressed in
      biliary atresia and analyzing the pattern of expression may lead to a better
      understanding of the pathogenesis. Liver tissues were taken from a recipient with
      biliary atresia and a normal donor during liver transplantation. Total RNA was
      extracted from each sample and reversely transcribed to cDNA. Then radiolabeled
      cDNA probe pools were made by random primed DNA labeling method and used for
      screening of differentially expressed genes by hybridizing with expressed
      sequence tags (EST) dot blot panel. Northern blot hybridization was done to
      confirm that these genes are also differentially expressed in other liver
      tissues. Among 1730 EST clones, 26 cDNA clones were significantly overexpressed
      in biliary cirrhosis, while 2 clones were significantly decreased in biliary
      atresia. By Northern blot hybridization, the results of tissue inhibitor of
      metalloproteinase (TIMP)-1 and IGFBP-2 were well correlated with differential EST
      screening (DES). This study identified the pattern of differentially expressed
      genes in the biliary cirrhosis due to biliary atresia using DES technique.

PMID- 12808328
TI  - De novo chromosomal aberrations in the fetus; genetic counseling and clinical
      outcome.
AB  - The aim of this study was to examine the incidence and clinical outcome of de
      novo chromosomal aberrations retrospectively and provide useful data for genetic
      counseling in the prenatal cytogenetic diagnosis. We found 17 cases of de novo
      chromosomal aberrations in 5501 cases of prenatal cytogenetic analysis and
      reviewed the karyotype, further study, medical records, fetal ultrasound findings
      and clinical outcomes. Out of the 17 de novo chromosomal aberrations, 5 had
      balanced reciprocal translocations and 12 had unbalanced translocations
      characterized as deletion, addition, or marker. In the case of the five balanced
      reciprocal translocations, 3 cases without abnormal ultrasound findings were
      carried to term after comprehensive genetic counseling. Neonates were
      phenotypically normal and clinical examinations were normal. Two cases with
      abnormal ultrasound findings were terminated therapeutically. Twelve cases of
      unbalanced translocations were terminated except one case with a mosaic marker
      chromosome. High resolution fetal ultrasound and detailed cytogenetic and
      molecular study will be adjunctive tools for predicting the karyotype/phenotype
      correlations of fetuses with de novo chromosomal aberrations, although they have
      limitation to find all phenotypic effects.

PMID- 12808329
TI  - Differential expression of placenta growth factors and their receptors in the
      normal and pregnancy-induced hypertensive human placentas.
AB  - Placental development requires extensive angiogenesis and the invasion of the
      maternal decidua by the trophoblasts. Adequate and organized interaction of
      vascular endothelial growth factors (VEGF), placenta growth factors (PlGF), and
      their receptors are essential for a normal development and function of the
      placenta. In this study, we evaluated the expressions of PlGFs and their
      receptors, mRNAs by Northern blotting, in situ hybridization and RT-PCR in the
      normal and pregnancy-induced hypertensive (PIH) placentas. The expression level
      of PlGF-2 mRNA was lower in the PIH placentas compared to control as assessed by
      Northern blotting and in situ hybridization. PlGF mRNA was mainly localized to
      the vasculosyncytial membrane of placental villi and villous stroma. The
      expression of PlGF receptor-1 (PlGFR-1) was significantly increased in the PIH
      placentas compared to the normal ones. These results suggest that the alteration
      of PlGF-2 and PlGFR-1 mRNA expressions in the placenta are related to the
      pathogenesis of PIH.

PMID- 12808330
TI  - Effects of ylang-ylang essential oil on the relaxation of rat bladder muscle in
      vitro and white rabbit bladder in vivo.
AB  - Current and primary treatment modality in overactive bladder includes the
      administration of anticholinergics. The demand for new agents has been rising
      since anticholinergics have proven to come with many side effects. This study was
      designed to investigate the effects of ylang-ylang essential oil (YYEO) on the
      relaxation of urinary bladder muscle in vitro and in vivo. Effects of YYEO were
      assessed on resting tension, and electrical field stimulation- and various drug
      induced contraction in vitro by checking the isometric tension changes of muscle
      strips and same procedures were repeated in the presence of methylene blue, Nw
      Nitro-L-arginine methyl ester hydrochloride (L-NAME), or N-ethylmaleimide, and in
      vivo. YYEO decreased significantly the contractility of strips. There was no
      statistically significant difference between the treated group only with YYEO and
      the pretreated group with YYEO and methylene blue or L-NAME. When N
      ethylmaleimide was employed, there was a statistically significant decrease in
      the rate of contraction. In vivo studies showed the same results compared with in
      vitro study. The results of this study indicate that YYEO has a relaxing effect
      on the bladder, and such mechanism is thought to be brought about by a pathway
      mediated by c-AMP.

PMID- 12808331
TI  - Intercellular adhesion molecule-1 polymorphisms in Korean patients with Behcet s
      disease.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is expressed on vascular endothelial
      cells and its expression increases during the inflammatory response in patients
      with active Behcet's disease (BD). The ICAM1 gene mutations are associated with
      BD in Caucasians, but clinical features of the mutation phenotype are unknown. We
      analyzed ICAM1 polymorphisms in Korean BD patients to determine if there was an
      association between particular mutations and clinical symptoms. The prevalence of
      ICAM1R241G and ICAM1K469E polymorphisms was determined among 197 patients with BD
      and 248 healthy controls using BsrG1 and BstU1 PCR-RFLP. The frequency of both
      genotypes ICAM1469 * K/ * E and ICAM-1469 * E/ * E was significantly higher in BD
      patients compared with controls (66.0% vs 52.4%, p=0.004, OR=1.28, 95% CI 1.08
      1.50) and the allele frequency of ICAM1469 * E was higher in patients with skin
      lesions (0.41), genital ulcers (0.41), vasculitis (0.43), ocular lesions (0.41)
      and arthritis (0.39) than in controls (0.31). Only one heterozygote, ICAM1241G/R,
      was detected in BD patients but the ICAM1241 * R mutation was not found in any of
      the 248 healthy controls. These results show that the ICAM1 mutation is
      associated with BD susceptibility, and is another genetic risk factor for BD
      among the Korean population.

PMID- 12808332
TI  - The association of subjective stress, urinary catecholamine concentrations and PC
      game room use and musculoskeletal disorders of the upper limbs in young male
      Koreans.
AB  - The use of PCs can cause health problems, including musculoskeletal disorders
      (MSDs) of the upper limbs. This study was performed to investigate whether using
      PCs in PC game rooms may induce MSDs of the upper limbs. 284 young male Koreans
      were included. A self-administered, structured questionnaire was used to gather
      information about game room use, perceived subjective stress, and the symptoms
      related to MSDs. Urinary concentrations of epinephrine, norepinephrine, and
      dopamine were measured in spot urine. The symptom prevalence of MSDs of the upper
      limbs increased according to the increase of the duration of game room use. The
      intensity of perceived subjective stress showed a significant dose-response
      relationship with the frequency of MSDs symptoms in neck and shoulder areas.
      However, the urinary level of catecholamines was not significantly correlated
      with the symptom prevalence of MSDs in the upper limbs. These findings suggest
      that using PCs in game rooms produce physical stress on the upper limbs, strong
      enough to induce MSDs.

PMID- 12808333
TI  - Molecular relatedness between isolates Yersinia pseudotuberculosis from a patient
      and an isolate from mountain spring water.
AB  - A 40-yr-old buddhist monk was admitted to the hospital with abdominal pain,
      fever, and confusion. He had a history of drinking untreated mountain spring
      water in his temple, and experienced the above symptoms for several days before
      admission. In past medical history, he had suffered from hepatic cirrhosis.
      Yersinia pseudotuberculosis was isolated from his blood and ascitic fluid. The
      mountain spring water that he had ingested was cultivated and Y.
      pseudotuberculosis was also isolated. For identification of pathogenic Y.
      pseudotuberculosis, each isolate from the three sources (blood, ascitic fluid,
      and drinking water) was also analysed for the inv gene for Y. pseudotuberculosis
      and the virF gene for virulent plasmid by PCR. All strains were positive for both
      the virF and the inv genes and also positive for autoagglutination test. For
      relationship study, each isolate from the three sources was also analysed with
      serotyping and restriction endonuclease analysis of virulence plasmid DNA (REAP)
      using BamHI. All belonged to the serotype 4b and REAP pattern D. Thus, all these
      findings supported that the mountain spring water was the source of the Y.
      pseudotuberculosis infection in this case.

PMID- 12808334
TI  - A case of gastroenteritis associated with gastric trichuriasis.
AB  - A rare human case of gastroenteritis and eosinophilic ascites associated with
      gastric trichuriasis is described. The patient was a 32-yr-old woman who was
      working in a farm near Pohang, Korea. She complained of abdominal pain, diarrhea,
      and vomiting. Endoscopic examination found focal linear hyperemia on the mucosa
      of the stomach antrum, and endoscopic biopsy confirmed eosinophilic inflammation
      of the mucosa and submucosa of the stomach, terminal ileum, and cecum. The biopsy
      specimen of the stomach included a female Trichuris trichiura which was covered
      by many inflammatory cells on its surface. Ascites and intestinal wall thickening
      was found by CT scan, and Douglas pouch centesis aspirated bloody ascites which
      included many eosinophils. She was medicated with prednisolone and albendazole
      and cured. She is the first case of eosinophilic inflammation of the
      gastrointestinal tract and ascites associated with trichuriasis in the stomach.

PMID- 12808335
TI  - Vesico-ileosigmoidal fistula caused by diverticulitis: report of a case and
      literature review in Japan.
AB  - Enterovesical fistula is a relatively uncommon complication of colorectal and
      pelvic malignancies, diverticulitis, inflammatory bowel disease, radiotherapy,
      and trauma in Asian countries. A case of vesico-ileosigmoidal fistula and a
      literature review of this disease in Japan are presented. A 70-yr-old male was
      referred with complaints of urinary pain and pneumaturia. On admission, urinary
      tract infection and pneumaturia were presented. A barium enema demonstrated
      multiple diverticulum in his sigmoid colon and the passage of contrast medium
      into the bladder and ileum. Under the diagnosis of vesico-ileosigmoidal fistula
      due to suspected diverticulitis of the sigmoid colon, sigmoidectomy and partial
      resection of the ileum with partial cystectomy were performed. The histopathology
      revealed diverticulosis of the sigmoid colon with diverticulitis and development
      of a vesico-ileosigmoidal fistula. No malignant findings were observed. Until the
      year 2000, a total of 173 cases of vesico-sigmoidal fistula caused by
      diverticulitis had been reported in Japan. Pneumaturia and fecaluria are the most
      common types, presenting symptoms in 63% of the cases. Computed tomography, with
      a sensitivity of 40% to 100%, is the most commonly used diagnostic study. For
      patients with vesico-sigmoidal fistula, resection of the diseased sigmoid colon
      and partial cystectomy with primary anastomosis are the safest and most
      acceptable procedures, leading to the best results.

PMID- 12808336
TI  - Leakage of jejunal end of roux limb after total gastrectomy: management with a
      placement of a covered metallic stent: case report.
AB  - Postoperative leakage is a serious complication in patients after gastric
      surgery. It can lead to a rapid deterioration in the patient's condition and
      quality of life. Treatment is guided by the type of anastomosis and the patient's
      clinical status. The role of interventional radiology in gastrointestinal tract
      is evolving. Metallic stent placement has shown encouraging results for the
      palliation of gastrointestinal tract obstruction and fistula in malignant
      patients. We encountered a case of the leakage of jejunal end of Roux limb after
      total gastrectomy. This patient required a drainage procedure with long-term
      parenteral nutrition. We performed peroral placement of a covered metallic stent
      to avoid surgery and long-term parenteral nutrition, and he resumed adequate oral
      intake immediately after stent placement. This minimally invasive procedure is
      very promising for the treatment of a gastrointestinal fistula to avoid surgery
      and long-term parenteral nutritional support in selected cases.

PMID- 12808337
TI  - Successful treatment of left atrial auricular abscess.
AB  - Mural endocarditis causing myocardial abscess without valvular involvement is
      very rare. We report an unusual case of left atrial auricular abscess which was
      successfully treated by surgical resection, treatment with antibiotics, and
      mediastinal irrigation. A 9-yr-old female patient with previous history of
      urinary tract infection was admitted because of persistent fever.
      Echocardiography and magnetic resonance imaging revealed massive pericardial
      effusion and a mass lesion at the left upper cardiac border. Pericardiocentesis
      isolated Staphylococcus aureus on culture. The patient underwent mass removal
      under cardiopulmonary bypass. The mass was located in the left atrial auricle
      with fibropurulent abscess formation inside. Postoperative mediastinal irrigation
      was performed using povidone iodine solution. Pathological examination of the
      mass showed organized thrombi with chronic fibrosing mural endocarditis.

PMID- 12808338
TI  - A case of Cushing s syndrome in pregnancy secondary to an adrenal cortical
      adenoma.
AB  - Cushing  s syndrome in pregnant women is rare and difficult to be diagnosed
      because of the syndrome's association with oligomenorrhea or amenorrhea and the
      changes in cortisol metabolism during normal pregnancy. Cushing syndrome in
      pregnancy is usually confused with complicated pregnancy, such as preeclampsia or
      gestational diabetes, and its rarity leads to a low degree of clinical suspicion,
      often delaying diagnosis. We experienced a case of Cushing  s syndrome in
      pregnancy, which had been considered as the severe preeclampsia and gestational
      diabetes due to uncontrolled hypertension and hyperglycemia. The pregnancy was
      terminated with an emergency cesarean operation at 30 weeks of gestation because
      of severe preeclampsia. In consequence of the evaluation about the Cushing  s
      syndrome after delivery, the adrenal cortical adenoma of right adrenal gland was
      diagnosed and laparoscopic adrenalectomy was performed.

PMID- 12808339
TI  - Localized amyloidosis of seminal vesicle and vas deferens: report of two cases.
AB  - We reported localized amyloidosis involving seminal vesicles and vasa deferentia,
      which was found in two patients with prostatic adenocarcinoma. A 60-yr-old (Case
      1) and a 59-yr-old (Case 2) man came to our hospital with elevation of serum
      prostate-specific antigen (PSA) and biopsy proven carcinoma, respectively. MRI
      revealed multiple irregular foci of low signal intensity in the prostates as well
      as in both seminal vesicles and vasa deferentia on T2-weighted imaging,
      suggesting prostatic carcinoma with extension to both seminal vesicles and vasa
      deferentia in both cases. Under the clinical diagnosis of stage III prostatic
      adenocarcinoma, a radical prostatectomy was performed in both patients.
      Microscopically, Gleason score 7 adenocarcinoma was observed in both patients. In
      addition, isolated amyloidosis of both seminal vesicles and vasa deferentia was
      found without carcinoma involvement. Localized amyloidosis in the seminal
      vesicles, which is considered as senile process, has been occasionally reported
      in the autopsy and in the surgical specimens. Amyloid deposition in the vas
      deferens has also been reported in the literature, however, the deposition
      mimicking extension of carcinoma has not been reported. In this report, two cases
      of isolated amyloidosis of the seminal vesicles and vasa deferentia are described
      with electron microscopic study and literature review.

PMID- 12808340
TI  - Bizarre leiomyoma of the scrotum.
AB  - Scrotal leiomyomas with atypical bizarre nuclei are rare, which might be
      misdiagnosed as malignant tumor. We describe a case of scrotal bizarre leiomyoma
      in a 65-yr-old man. The tumor was a 1 cm-sized, well circumscribed, oval mass
      arising from the tunica dartos muscle. Histologically, it was formed by whorling
      bundles of fusiform cells with occasional atypical, pleomorphic nuclei and pseudo
      inclusions. Mitosis was not found. Although morphologically atypical, scrotal
      bizarre leiomyomas take on a biologic behavior not different from that of
      conventional leiomyoma, they should be distinguished from leiomyosarcoma to avoid
      unnecessary treatment.

PMID- 12808342
TI  - Gianotti-Crosti syndrome following Japanese encephalitis vaccination.
AB  - We report a three-year-old Korean boy who presented with itching symmetrical
      erythematous macules and papules on his face, trunk, and extremities for 1 week.
      Lymphadenopathies were detected on physical examination. He was vaccinated
      against Japanese B Encephalitis (JE) 1 day before developing skin rashes. The
      patient  s serum JE antibody titer by hemagglutinin inhibition (HI) test was
      1:40. Under the diagnosis of Gianotti-Crosti syndrome following JE vaccination,
      he was conservatively treated with an antihistamine agent, and his symptoms were
      all cleared 2 weeks after treatment.

PMID- 12808341
TI  - Nasal rhinoscleroma in a nonendemic area: a case report.
AB  - Rhinoscleroma is a chronic, granulomatous infectious lesion most frequently
      affecting the respiratory tract mucosa. This disease is endemic to Africa,
      Central and South America, South Central and Eastern Europe, the Middle East, and
      China. We report an extremely rare disease of nasal rhinoscleroma in Korea. The
      patient was a 63-yr-old man, who suffered from chronic nasal obstruction and
      septal deviation. Characteristic histology from a nasal biopsy was proven and
      special stains for bacteria were employed: periodic acid-Schiff, Warthin-Starry
      silver, Giemsa, and Gram stains. Isolation of Klebsiella rhinoscleromatis from a
      culture of nasal discharge was failed, but ultrastructural examination of
      numerous phagocyzed bacilli in the Mikulicz cells confirmed the diagnosis. The
      histiocytic nature of the Mikulicz cells was confirmed, using CD 68 and alpha-1
      antitrypsin, and by the ultrastructural features of Mikulicz cells. Here, we
      emphasize the recognition of this rare entity in nonendemic regions, frequently
      leading to delayed diagnosis.

PMID- 12808343
TI  - Delusional parasitosis as 'folie a deux'.
AB  - Delusional parasitosis is characterized by the unshakeable belief of being
      infested with tiny (microscopic) insects. Patients spend much time trying to get
      rid of the bugs and suffer from these symptoms. Patients prefer to go to
      dermatologists because they have a strong conviction over the presence of a
      somatic disease and do not accept any psychiatric advice for their complaints.
      Folie a deux or shared psychotic disorder (SPD) is a relatively rare syndrome,
      which has long attracted clinical attention. Delusional parasitosis is associated
      in 5-15% of SPD and can run within a family. We experienced delusional
      parasitosis as Folie a Deux between a mother and her son and successfully treated
      them through early psychiatric intervention. We believe that attention should be
      drawn to DP with SPD.

PMID- 12808344
TI  - Persistence of the nitric oxide pathway in the aorta of hypercholesterolemic
      apolipoprotein-E-deficient mice.
AB  - The markers of the bioavailability of NO (endothelium-dependent relaxation to
      acetylcholine and cyclic GMP content) in the thoracic aorta of apolipoprotein-E
      deficient (ApoE KO) mice, 20 weeks old with enriched cholesterol diet or 35 weeks
      old on regular chow, are not decreased, in contrast with other models of
      atherosclerosis. However, severe hypercholesterolemia, the presence of
      atherosclerotic lesions and increased NADPH oxidase activity have been reported
      as early as at 20 weeks of age. The present experiments were designed to test if
      an increased capacity of NO production in these mice explains this paradox. The
      expressions of the 3 isoforms of NO synthase (NOS) were compared in ApoE KO and
      C57Bl/6J mice using Western blot and localized by immunohistochemistry. No
      adaptive increase in the expression of NOS was detected in ApoE KO mice. NO
      bioavailability could also be preserved by upregulation of enzymes involved in
      redox status such as CuZn or Mn superoxide dismutase and catalase. However, these
      enzymes were less expressed in ApoE KO mice than in control mice. These results
      highlight that ApoE KO mice represent an atypical model of atherosclerosis.

PMID- 12808345
TI  - Different growth properties of neointimal and medial smooth muscle cells in
      response to growth factors.
AB  - Different smooth muscle cell phenotypes coexist in arteries. The majority of
      cells cultured from a normal rat aortic media have a spindle-shaped phenotype
      while cells isolated from an intimal thickening 15 days after endothelial injury
      show a distinct epithelioid phenotype. These two phenotypes express their own
      specific set of genes and differ in their proliferation and migration
      characteristics. We studied growth factor-induced DNA synthesis in both
      phenotypes and investigated the potential mechanisms behind the differences in
      growth characteristics. Insulin-like growth factor-I (IGF-I), platelet-derived
      growth factor (PDGF-BB), and basic fibroblast growth factor (FGF) increased
      thymidine incorporation in both phenotypes, but the increase was markedly
      stronger in neointimal cells than in medial cells. Northern blot analysis 30 min
      after growth factor stimulation showed that c-FOS and c-JUN mRNAs were induced
      more strongly in neointimal than in medial cells. IGF-I receptor and PDGF-R beta
      levels were higher in neointimal cells than in medial cells, but the FGF receptor
      level was not different between the cell types. In summary, our results indicate
      that neointimal cells are more sensitive to growth factors than medial cells,
      likely due to a higher expression of IGF-I receptor and PDGF-R beta. Our results
      provide insight into the mechanism by which epithelioid cells play a primary role
      in vascular neointima formation.

PMID- 12808346
TI  - The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester
      on neuropeptide-induced vasodilation and protein extravasation in human skin.
AB  - Endogenous neuropeptides released from nociceptors can induce vasodilation and
      enhanced protein extravasation (neurogenic inflammation). The role of nitric
      oxide (NO) in the induction of neurogenic inflammation is controversial. In this
      study, dermal microdialysis was used in awake humans (n = 39) to deliver
      substance P (SP; 10(-7) and 10(-6)M) or calcitonin gene-related peptide (CGRP; 5
      x 10(-7)M and 2 x 10(-6)M). Neuropeptide-induced local and axon reflex erythema
      was assessed by laser Doppler imaging. Total protein concentration in the
      dialysate was measured to quantify local protein extravasation. The responses
      were assessed in the absence and the presence of the nitric oxide synthase
      inhibitor, N-nitro-L-arginine-methyl ester (L-NAME) added to the perfusate at
      concentrations of 5, 10 or 20 mM. L-NAME (5 mM) applied via the dialysis
      catheters reduced local blood flow by approximately 30%. In addition, L-NAME
      inhibited SP-induced vasodilation by about 40% for 10(-7)M SP and 30% for 10(-6)M
      SP (n = 11, p < 0.01). In contrast, CGRP-induced vasodilation was only marginally
      inhibited by L-NAME. SP, but not CGRP, provoked a dose-dependent increase in
      protein extravasation. L-NAME (5 mM) inhibited this increase by up to 40% for
      both SP concentrations used (n = 11, p < 0.01). Higher concentrations of L-NAME
      did not further reduce SP- or CGRP-induced vasodilation or SP-induced protein
      extravasation. Exogenously applied SP induces vasodilation and protein
      extravasation, which is partly NO mediated, whereas CGRP-induced vasodilation
      appears to be NO independent.

PMID- 12808347
TI  - Co-infection with Chlamydia pneumoniae and Helicobacter pylori results in
      vascular endothelial dysfunction and enhanced VCAM-1 expression in apoE-knockout
      mice.
AB  - BACKGROUND: Upregulation of proinflammatory endothelial cell adhesion molecules
      and decreased bioactivity of endothelial nitric oxide (NO) are important in the
      pathogenesis of atherosclerosis. We investigated the effects of co-infection with
      Chlamydia pneumoniae and Helicobacter pylori on these two events in apoE-KO mice.
      METHODS: Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4
      groups. The first 2 groups were infected with either C. pneumoniae or H. pylori,
      while the 3rd group was infected with both C. pneumoniae and H. pylori. Mice from
      the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal
      aortas were harvested after 10 weeks, and staining for vascular cell adhesion
      molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by
      immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to
      methacholine were studied in organ chambers in the absence and presence of L
      NAME. The plasma levels of nitrate/nitrite were measured. RESULTS: Staining for
      VCAM-1 was more intense at the branching sites of aortas from mice with co
      infection than in mono-infected or noninfected apoE-KO mice. The relaxation
      responses to methacholine and the plasma levels of nitrate/nitrite were
      significantly less in the co-infected group than in the other groups (p < 0.05).
      CONCLUSION: Co-infection of apoE-KO mice with C. pneumoniae and H. pylori seems
      to be associated with impaired bioactivity of endothelial NO and increased
      expression of VCAM-1 at branching sites. The findings may suggest an additive
      interaction of these pathogens in atherogenesis.

PMID- 12808348
TI  - Heterogeneity in the acute control of vascular protein synthesis in vivo.
AB  - In response to both hemodynamic and neurohumoral changes, the cardiovascular
      system remodels and this process could contribute to end organ damage. The aim of
      this study was to determine the early in vivo interactions between 3 systems
      known to contribute to vascular hypertrophic remodeling, in conduit and
      resistance arteries. Exogenous angiotensin II, norepinephrine and endothelin 1
      administration elevated protein synthesis in the aorta and in small mesenteric
      arteries. In small arteries, the effect of angiotensin II was blocked by
      angiotensin II type 1, alpha-adrenergic and endothelin receptor antagonists,
      while only the alpha-adrenergic and endothelin receptor antagonists inhibited the
      effect of norepinephrine. Moreover, only the endothelin receptor antagonist
      significantly blunted the effect of exogenous endothelin on protein synthesis. In
      the aorta, the stimulation of angiotensin II on protein synthesis was also
      inhibited by the 3 antagonists. However, only the alpha-adrenoceptor antagonist
      blunted the response to norepinephrine, and the 3 antagonists prevented the
      endothelin-induced elevation of protein synthesis. The blood pressure effects of
      the drugs did not correlate with their capacity to stimulate or inhibit vascular
      protein synthesis. In conclusion, interactions in the control of protein
      synthesis are heterogeneous along the vascular tree. In small arteries, the
      interaction is linear with endothelin as the downstream effector. In the aorta,
      the local sympathetic nervous system appears to control protein synthesis. The
      heterogeneity in downstream effectors should be considered in studies
      investigating signaling events related to protein synthesis, which is used as an
      early marker of hypertrophy.

PMID- 12808349
TI  - Enhancement of cell viability in cryopreserved rat vascular grafts by
      administration of regenerating gene (REG) inducers.
AB  - The regenerative capacity of viable cells remaining in cryopreserved vascular
      allografts is still unclear. Recently, the regenerating gene (REG) has been
      documented to play an important role in various regenerating tissues. Here we
      show the possibility of REG induction for the enhancement of cryopreserved
      vascular allograft viability. Cryopreserved rat aortae were isografted or
      allografted heterotopically. Fresh isografts were also tested. The transplants
      were retrieved 3, 6, 9, and 12 days after implantation and the intragraft REG
      mRNA was measured by a real-time quantitative reverse transcriptional polymerase
      chain reaction method. REG expression was not detected before implantation. REG
      expression in cryopreserved isografts gradually increased after transplantation,
      whereas in fresh isografts or cryopreserved allografts it decreased over time
      after initial expression. Daily administration of 0.5 g/kg nicotinamide (an agent
      known to be a potent inducer of REG) induced intragraft REG mRNA in cryopreserved
      allografts (p < 0.05) accompanied by augmentation of the intragraft cell
      population. Daily administration of 0.5 mg/kg FK506 (an immunosuppressant)
      induced intragraft REG mRNA both in cryopreserved isografts and allografts (p <
      0.01). We conclude that REG-inductive therapy shows promise as a novel strategy
      for enhancing the viability of vascular allografts. Moreover, FK506 may be
      involved in tissue regeneration as well as immunosuppression.

PMID- 12808350
TI  - Requisite role of p38 MAPK in mural cell recruitment during angiogenesis in the
      rat aorta model.
AB  - During the early stage of angiogenesis, neovascular sprouts are composed
      primarily of endothelial cells. As they mature, microvessels acquire a coating of
      mural cells, which are critical for the development and maintenance of a
      functional vasculature. Though growth factor regulation of mural cell recruitment
      has been extensively investigated, the intracellular signaling events involved in
      this process remain poorly understood. Among the intracellular kinases implicated
      in angiogenesis, the p38 MAPK has been shown to transduce signals critical for
      vascular remodeling and maturation. The rat aorta model of angiogenesis was used
      to further investigate the role of this signaling pathway in the recruitment of
      mural cells during angiogenesis. The p38 MAPK inhibitor SB203580 selectively
      blocked mural cell recruitment, resulting in the formation of naked endothelial
      tubes without mural cells. SB203580 inhibited angiopoietin-1-induced mural cell
      recruitment without influencing angiopoietin-1-stimulated endothelial sprouting.
      Adenoviral vector-mediated expression of a dominant negative form of p38 MAPK
      significantly reduced mural cell recruitment, whereas overexpression of a
      constitutively activated form of MKK6, an upstream activator of p38 MAPK,
      increased mural cell number. These results indicate that the p38 MAPK signaling
      pathway plays a critical role in mural cell recruitment during neovascularization
      and may represent a therapeutic target in angiogenesis-related disorders.

PMID- 12808351
TI  - Conducted vasoconstriction is reduced in a mouse model of sepsis.
AB  - The ability of an arteriole to conduct vasomotor responses along its length
      contributes to the control of organ perfusion. Sepsis, a systemic inflammatory
      response to infection, may compromise this control. We aimed to determine whether
      sepsis, induced by cecal ligation and perforation (CLP), reduces conducted
      vasoconstriction 24 h post-CLP. We locally stimulated mouse cremaster arterioles
      with KCl, measured the resulting local and the conducted constriction (500 microm
      upstream) and, based on these measurements, determined the communication ratio
      (CR(500)) as an index of the conducted response. Sepsis significantly reduced the
      CR(500) from 0.75 to 0.20. Based on a mathematical model, this reduction was
      predicted to have a significant impact on blood flow control. In septic mice,
      either a 1-hour washout of the cremaster muscle with physiological saline or a
      treatment of this muscle with the tyrosine kinase inhibitor PP-2 (100 nM)
      restored the CR(500) to the control level. Treatment of septic arterioles with
      the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (100
      microM) partially restored the CR(500) from 0.2 to 0.4. In control mice,
      lipopolysaccharide (LPS; 10 microg/ml) superfused over the cremaster muscle for 1
      h reduced the CR(500); the nitric oxide (NO) donor S-nitroso-N-acetyl
      penicillamine (50 microM) also reduced the CR(500). Thus, LPS and NO could be two
      factors mediating reduced conduction of vasoconstriction in sepsis. We conclude
      that sepsis reduces the KCl-induced conducted vasoconstriction in the mouse
      cremaster muscle by a tyrosine kinase- and nitric oxide- dependent mechanism.

PMID- 12808352
TI  - Evidence for a differential cellular distribution of inward rectifier K channels
      in the rat isolated mesenteric artery.
AB  - The distribution of functionally active, inwardly rectifying K (K(IR)) channels
      was investigated in the rat small mesenteric artery using both freshly isolated
      smooth muscle and endothelial cells and small arterial segments. In Ca(2+)-free
      solution, endothelial cells displayed a K(IR) current with a maximum amplitude of
      190 +/- 16 pA at -150 mV and sensitivity to block with 30 microM Ba(2+) (n = 7).
      In smooth muscle cells, outward K current was activated at around -47 +/- 3 mV,
      but there was no evidence of K(IR) current (n = 6). Furthermore, raising
      extracellular [K(+)] to either 60 or 140 mM, or applying the alpha(1)
      adrenoceptor agonist phenylephrine (PE; 30 microM), failed to reveal an inwardly
      rectifying current in the smooth muscle cells, although PE did stimulate an
      iberiotoxin-sensitive outward K current (n = 4). Exogenous K(+) (10.8-16.8 mM)
      both relaxed and repolarized endothelium-denuded segments of the mesenteric
      artery contracted with PE. These effects were depressed by 100 microM ouabain but
      unaffected by either 30 microM BaCl(2) or 3 microM glibenclamide. These data
      suggest that functional, inwardly rectifying Ba(2+)-sensitive channels are
      restricted to the endothelial cell layer in the rat small mesenteric artery.

PMID- 12808353
TI  - Attenuation of canine cerebral vasospasm after subarachnoid hemorrhage by protein
      kinase C inhibitors despite augmented phosphorylation of myosin light chain.
AB  - The purpose of the present study is to assess the roles of protein kinase C (PKC)
      isoforms, especially PKC delta and alpha, and 20-kD myosin light chain (MLC(20))
      phosphorylation in the mechanism of cerebral vasospasm following subarachnoid
      hemorrhage (SAH). We had shown that those PKC isoforms are involved in the
      development of cerebral vasospasm. Using PKC isoform-specific inhibitors in a
      'two- hemorrhage' canine model, we examined changes in the development of
      cerebral vasospasm, translocation of PKC isoforms and MLC(20) phosphorylation
      level in canine basilar arteries. A PKC inhibitor (5 microM rottlerin for PKC
      delta or chelerythrine for PKC alpha) was injected into the cisterna magna on day
      4 before the second hemorrhage. The treatment was continued daily until day 7.
      Rottlerin inhibited the initial phase of vasospasm and PKC delta translocation,
      but did not significantly inhibit PKC alpha translocation. Chelerythrine
      inhibited cerebral vasospasm, and the translocation of both PKC delta and alpha
      throughout the entire course of the study. Although cerebral vasospasm after SAH
      was inhibited by each PKC inhibitor, the MLC(20) phosphorylation level remained
      elevated as in the untreated hemorrhage-control study. We conclude that cerebral
      vasospasm following SAH depends on PKC delta and alpha, while the enhancement of
      MLC(20) phosphorylation contributes little to this form of vasospasm.

PMID- 12808355
TI  - [From Swiss herbs to the global plant system and individual use--a biographic
      approach to Alfred Vogel].
AB  - BACKGROUND: Even 100 years after the birth of Alfred Vogel there is a lack of
      reliable data about his life as a non-doctoral therapist in the fields of
      naturopathy and phytotherapy. OBJECTIVE: Which documents about A. Vogel do exist,
      which facts do they prove about his career and which interpretations of his point
      of view of phytotherapy do they allow. MATERIALS AND METHODS: With the methods in
      medical history (heuristic, critic, interpretation) video, audio and written
      documents from the A. Vogel Museum and A. Vogel publisher in Teufen, the A. Vogel
      collection in the Museum in Aesch and the Bioforce AG in Roggwil have been
      examined. RESULTS: From 1923 to 1932 A. Vogel runs a grocer's shop or a herb and
      health-food store in Basel and later Bern, Zurich and Solothurn. The economic
      success of his health-food stores and his interest in the field of naturopathy
      enable him to take part in a training to become a 'natural doctor' and in 1933 he
      is registered by the 'Natural Doctors Association of Switzerland'. From 1935 on
      he is working as a nutritionalist in his own spa pension in Trogen and produces
      plant extracts in his 'Laboratory Bioforce'. From 1937 to 1957 he has a spa hotel
      in Teufen and is producer of extracts from fresh plants. He is able to travel all
      continents of the world from 1958 on, in order to observe customs and medical
      habits of different tribes. He writes about his findings in his own magazine and
      books. His knowledge about the usage of herbs in different cultures inspires his
      production of herbal extracts in his company. In 1963, to meet the increasing
      sales of his products, he founds the <<Bioforce AG>> where he, until the early
      1990s, takes part in the adjustment of the recipes to the new pharmaceutic
      medical standards. CONCLUSION: Because of his work as a 'natural doctor' A. Vogel
      becomes one of Switzerland's best known non-doctoral therapists in the 20th
      century. The publication of his collected wisdom in a lay-like language is a
      contribution to the tradition and popularity in this field through which, as well
      as through the development of extracts from fresh plants, he becomes a promoter
      of phytotherapy.

PMID- 12808356
TI  - [History of a plant: the example of Echinacea].
AB  - In comparison with other medicinal plants, the history of use of Echinacea is
      relatively short. The plant originates from North America and was employed by the
      indigenous Indians. The first archaeological evidence dates from the 18th
      century. Included in the name Echinacea or purple coneflower are several species
      of the Asteraceae family: Echinacea purpurea (L.) Moench, Echinacea angustifolia
      DC. and Echinacea pallida (Nutt.) Nutt. Information about the use of the plant
      from traditional healers ranges from external application for wounds, burns and
      insect bites to the chewing of roots for toothache and throat infections, and
      internal application for pain, coughs, stomach cramps and snake bites. The
      interest of white settlers was also drawn to this medicinal plant. The first
      Echinacea preparation, known as Meyers Blood Purifier, arrived on the market
      around 1880, with rheumatism, neuralgia and rattlesnake bites as indications. At
      the beginning of the 20th century, Echinacea was the most frequently used plant
      preparation in the USA. Commercial cultivation was started in Germany around
      1939. The introduction and cultivation of Echinacea in Switzerland by A. Vogel
      was around 1950. Chemists and pharmacologists became interested in Echinacea and
      many constituents are now known, such as polysaccharides, echinacoside, cichoric
      acid, ketoalkenes and alkylamides. The extracts exhibit immunostimulant
      properties and are mainly used in the prophylaxis and therapy of colds, flu and
      septic complaints. Although there are over 400 publications concerning the plant
      and dozens of preparations of Echinacea n the market, the true identity of the
      active principles still remains open.

PMID- 12808357
TI  - [Indication and constitution in the phytotherapeutic qualitative concept].
AB  - In its original form, phytotherapy is based, among other things, on qualitative
      concept. Starting-point of the concept are the paired terms: warmth/cold and
      moisture/dryness. Young people tend to have a warm constitution and older
      individuals a cold constitution. There are, however, type-related differences.
      Illnesses progress in various phases. A simple cold, for example, can also be
      split into a cold and warm phase. These phases should be treated separately with
      different remedies.

PMID- 12808358
TI  - Systematic reviews of herbal medicines--an annotated bibliography.
AB  - OBJECTIVE: To provide a comprehensive collection and a summary of systematic
      reviews of clinical trials on herbal medicines. METHODS: Potentially relevant
      reviews were searched through the register of the Cochrane Complementary Medicine
      Field, the Cochrane Library, Medline, and bibliographies of articles and books.
      To be included articles had to review prospective clinical trials of herbal
      medicines; had to describe review methods explicitly; had to be published; and
      had to focus on treatment effects. Information on conditions, interventions,
      methods, results and conclusions was extracted using a pretested form and
      summarized descriptively. RESULTS: From a total of 79 potentially relevant
      reviews preselected in the screening process 58 met the inclusion criteria. 30 of
      the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus,
      and macular degeneration), hypericum (for depression) or garlic preparations (for
      cardiovascular risk factors and lower limb atherosclerosis). The quality of
      primary studies was criticized in the majority of the reviews. Most reviews
      judged the available evidence as promising but definitive conclusions were rarely
      possible. CONCLUSIONS: Systematic reviews are available on a broad range of
      herbal preparations prescribed for defined conditions. There is very little
      evidence on the effectiveness of herbalism as practiced by specialist herbalists
      who combine herbs and use unconventional diagnosis.

PMID- 12808359
TI  - [St. John' Wort (Hypericum perforatum L.)--multicompound preparations versus
      single substances].
AB  - Aqueous alcoholic extracts of St. John s wort are used for the treatment of mild
      to moderate depression. Recently, Hypericum extracts were also shown to inhibit
      the growth of various human malignant cells. We promote the hypothesis that the
      various biological activities of aqueous Hypericum extracts are based on
      synergistic interactions of all compounds present therein and not on the
      pharmacological activities of single compounds.

PMID- 12808360
TI  - [St. John's Wort (Hypericum perforatum): a plurivalent raw material for
      traditional and modern therapies].
AB  - St. John's Wort is one of the oldest and one of the best experimentally and
      clinically examined herbal remedies. In various medical cultures and medical
      systems--that is to say the regions of origin of Hypericum perforatum, like
      Europe, West Asia and North Africa--St. John's Wort has been used as a remedy for
      centuries. Preparations from St. John's Wort not only represent medical
      traditions but also ways of thinking, ideas and experiences from naturopathic
      healers (non-physicians) as well as patients. The complex multicompound with its
      evolutionary and coevolutionary developed composition and structure acts as a
      varied raw material for the production of quantitative and qualitative dissimilar
      remedies, which are multicompounds themselves. They differ not only analytically
      but also quite often in their effects. The certain and potential spectrum of
      internal and external uses includes gastrointestinal complaint and illness, skin
      disease, mucosal lesion, superficial injury, depressive upset and depression,
      somatoform disorders, restlessness, nervosity, convalescence, exhaustion, sleep
      disturbance and nursing treatment. The plurivalent character of the multicompound
      even enables a broad spectrum of activity. This might justify to prefer St.
      John's Wort to other drugs in a wide range of treatments: In tumor patients with
      depression the antioxidative effect and the experimentally documented induction
      of apoptosis could mean an additional advantage, and in depressive patients with
      coronary heart disease the same applies to the anti-inflammatory and
      antioxidative effects.

PMID- 12808361
TI  - [The common butterbur (Petasites hybridus)--portrait of a medicinal herb].
AB  - For hundreds of years butterbur (Petasites hybridus) has been used against many
      diseases. Modern indications are the prophylaxis of migraine, tension headache,
      spasms of the urogenital tract, gastro-intestinal tract and bile duct and
      hopefully hay fever and asthma in the near future. The petasines, the main
      components of butterbur, inhibit the synthesis of leucotrienes and decrease the
      intracellular concentration of calcium which explains the anti-inflammatory and
      spasmolytic properties of extracts of butterbur. Thanks to extraction with
      supercritical CO(2) the concentrations of the potentially hepatotoxic and
      carcinogenic pyrrolizidine alkaloids lie below the detection limits. Until now
      four cases of a reversible cholestatic hepatitis have been probably associated
      with long-term administration of butterbur (incidence of 1:175.000). It is
      unknown which components of butterbur are responsible for the long-term
      hepatotoxicity. Further side effects involve the gastrointestinal tract and are
      usually mild.

PMID- 12808362
TI  - [Arnica: new insights on the molecular mode of action of a traditional medicinal
      plant].
AB  - Preparations from Arnica flowers have been used in traditional medicine since a
      long time for the treatment of inflammatory diseases. Sesquiterpene lactones are
      considered as their main active compounds. Previously, it was shown that these
      natural products attack inflammatory processes at a very central point by
      inhibiting the transcription factors NF-kappa B and NF-AT at micromolar
      concentrations. Both transcription factors regulate the transcription of genes
      encoding for many inflammatory mediators. Thus, these new insights on their
      molecular mode of action are an important contribution for a better understanding
      of the antiinflammatory activity of preparations from Arnica. First clinical
      studies show that they can support the treatment of rheumatic diseases. The
      agreed use is important to avoid undesirable side effects.

PMID- 12808363
TI  - [Who is surprised by the healing power of prayer?].

PMID- 12808364
TI  - The placebo effect on mood and behavior: possible role of opioid and dopamine
      modulation of the hypothalamic-pituitary-adrenal system.
AB  - There has been an increasing interest in the placebo effect over the past several
      decades. The relationship between the placebo effect and the underlying
      mechanisms of the body that control and maintain health is still not well
      understood. Significant evidence suggests that endogenous opioids and dopamine
      are involved in the mechanisms of the placebo effect. The endogenous opioid and
      dopaminergic systems have been demonstrated to exert effects on the functional
      activity of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA system
      contributes to regulation of mood and behavior. The author suggests that opioid
      and dopamine modulation of the HPA system is one of the neurobiological
      mechanisms of the placebo effect on mood and behavior. To elucidate the
      underlying biological mechanisms of placebo effects and to study the use of
      placebo in clinical practice to improve health are two important and interrelated
      tasks. Future studies of the neurobiology of the placebo response may yield
      interesting and important results.

PMID- 12808365
TI  - [Development of a questionnaire for endogenous regulation--a contribution for
      salutogenesis research].
AB  - INTRODUCTION: Objective of this study was to develop a questionnaire for
      endogenous regulation (eR) and to evaluate its relevance in clinical and
      preventive medicine. The inventory included items about sleeping and waking,
      orthostatic regulation, thermoregulation, and circadian well-being. METHODS: 158
      age-matched women with diabetes (1/2, n = 53), breast cancer (n = 52) and healthy
      controls (n = 53) filled in the Havelhohe constitutional questionnaire (HKF1.0),
      and a 24-h-Oxford-FD3-ECG was recorded. RESULTS: We developed a twelve-items
      scale for eR, which is according to test theory an objective and reliable
      instrument (Cronbach-alpha: r alpha = 0.71, retest reliability: rt = 0.83). The
      validity analysis confirmed that the breast cancer and diabetic group show a
      lower eR than the control group (both p < 0.001). Furthermore, high eR is
      correlated with a 'rare tendency to feel quite low', 'less allergies', 'less
      period pains', and a 'shorter duration of breast cancer'. Therefore eR can be
      regarded as a marker for health and well-being. High eR correlates as well with
      personality traits as morningness, 'needing less time for thinking through',
      'being less unsure at important decisions', and 'being less confidential'. We can
      show first correlations between eR and the rhythmical marker 'nightly pattern
      predominance'. With both methods we are achieving for women until 60 years a
      satisfying discrimination between breast cancer and healthy individuals.
      CONCLUSIONS: We are achieving a first validation of our scale of endogenous
      regulation. Further studies for the evaluation of the conceptual, clinical,
      rehabilitative, and preventive medicine relevance of eR are necessary.

PMID- 12808366
TI  - Seasonal variation of lipid-lowering effects of complex spa therapy.
AB  - BACKGROUND AND OBJECTIVE: It has been shown that spa therapy has a lipid-lowering
      effect. Also, seasonal variations in spa therapy effects have been found for some
      outcome measures. The aim of the present study is to investigate whether the
      lipid-lowering effects of spa therapy as a complex health intervention also are
      subject to seasonal variation. METHOD: The effect of 3-week resident spa therapy
      at the Austrian spa Bad Tatzmannsdorf was studied in 395 patients with moderate
      musculoskeletal chronic pain over a time of 2 years. Spa therapy included
      balneotherapy, exercise therapy, and dietary measures. Total cholesterol (CHOL),
      HDL, LDL, triglycerides (TG), and the CHOL/HDL ratio were assessed at the
      beginning and end of therapy. RESULTS: Spa therapy was associated with a decrease
      of CHOL, HDL, and LDL (p < 0.001). TG and CHOL/HDL did not change. The decrease
      of lipids was smaller for older patients, females, and normal weight individuals.
      CHOL decrease showed a seasonal variation independent of weight loss (p = 0.04),
      being largest in fall (-6.1%) and smallest in spring (-2.4%). CHOL and CHOL/HDL
      for obese individuals showed the greatest decrease in winter (-10% for CHOL, -9%
      for CHOL/HDL ratio), whereas corresponding measures increased for normal-weight
      subjects. CONCLUSIONS: The lipid-lowering effect of spa therapy could be
      confirmed; it is partly moderated by season. The results suggest that the effect
      of some components of spa therapy such as exercise therapy, diet, and relaxation
      may be subject to seasonal variation.

PMID- 12808367
TI  - Kombucha: a systematic review of the clinical evidence.
AB  - AIM: Kombucha has become a popular complementary remedy. The aim of this
      systematic review was to critically evaluate the evidence related to its efficacy
      and safety. METHODS: Computerised literature searches were carried out to locate
      all human medical investigations of kombucha regardless of study design. Data
      were extracted and validated by the present author and are reported in narrative
      form. RESULTS: No clinical studies were found relating to the efficacy of this
      remedy. Several case reports and case series raise doubts about the safety of
      kombucha. They include suspected liver damage, metabolic acidosis and cutaneous
      anthrax infections. One fatality is on record. CONCLUSIONS: On the basis of these
      data it was concluded that the largely undetermined benefits do not outweigh the
      documented risks of kombucha. It can therefore not be recommended for therapeutic
      use.

PMID- 12808368
TI  - Characteristics and quality of systematic reviews of acupuncture, herbal
      medicines, and homeopathy.
AB  - BACKGROUND: We aimed to describe the approaches and characteristics of systematic
      reviews on three major complementary therapies and to assess their methodological
      quality. METHODS: Systematic reviews of clinical trials of acupuncture, herbal
      medicines, and homeopathy were identified from a database developed for the
      Cochrane Collaboration Complementary Medicine Field. Information on conditions,
      interventions, methods, results, and conclusions was extracted using a pre-tested
      form; methodological quality was assessed using the Oxman scale. RESULTS: 115
      reviews were included (39 on acupuncture, 58 on herbal medicine, 18 on
      homeopathy). Research questions were most specific in herbal medicine, and tended
      to be very general in homeopathy. The main comparison in most reviews was with
      placebo. The methodological quality of reviews was highly variable. Deficiencies
      were most frequent for the description of the selection process and the summary
      of the results of primary studies. CONCLUSION: Systematic reviews tend to
      approach different complementary therapies in different manner. Compared to a set
      of reviews on analgesic interventions methodological quality was slightly better
      on the average, but there is ample room for improvement in future complementary
      medicine reviews.

PMID- 12808369
TI  - Status epilepticus: a review of different syndromes, their current evaluation,
      and treatment.
AB  - BACKGROUND: Status epilepticus (SE) encompasses a wide range of seizure types
      with different clinical presentations, pathophysiologies, treatment imperatives,
      and outcomes. The most dramatic and life-threatening form, generalized convulsive
      status epilepticus, has been reviewed in all of these aspects, but other less
      common types of SE have been described less extensively. REVIEW SUMMARY:
      Definitions of generalized convulsive SE and its pathophysiology are reviewed
      briefly. Defining SE by a specific duration of seizures is controversial and has
      implications for studies and for clinical management. Several types of SE are
      different in their causes, presentations, and outcomes. Many are underdiagnosed.
      This article focuses on the pharmacology and clinical studies of several
      anticonvulsant medications used to treat SE. A protocol approach is not detailed.
      Rather, the clinical evaluation begins with meticulous diagnosis of the type of
      SE. Establishing the SE syndrome diagnosis and use of anticonvulsants with
      demonstrated effectiveness facilitate an appropriate treatment plan for
      individual patients. Recent developments in the basic science of SE raise the
      possibility of better treatments in the future. CONCLUSIONS: As there are many
      types of seizures, there are also many types of SE. Each has unique presentations
      and treatment considerations. Review of actual clinical data from SE treatment
      studies should be helpful in devising the best treatment for an individual
      patient.

PMID- 12808370
TI  - Thymectomy for myasthenia gravis: analysis of controversies--patient management.
AB  - BACKGROUND: Debate continues regarding the effectiveness of thymectomy in the
      treatment of nonthymomatous autoimmune myasthenia gravis primarily because there
      have been no controlled prospective studies. The debate is compounded by the lack
      of recognition that all thymectomies are not equal in extent or effectiveness and
      by the fact that all the studies are retrospective without common definitions of
      myasthenia gravis manifestations or response to therapy. In addition, the
      analysis of data is often inappropriate. REVIEW SUMMARY: Evidence is presented
      demonstrating that the extent of the various thymic resectional techniques is
      very variable and often incomplete and that the more complete the thymic
      resection the better the results. The indications for thymectomy, the selection
      of the technique of the resection, the reoperations issue, the perioperative
      management of the myasthenia gravis patient, morbidity and mortality, and
      appropriate methods of outcome research are also reviewed. CONCLUSION: In view of
      the impressive results associated with a complete thymic resection in the
      treatment of myasthenia gravis, patients should not be denied this operation
      because of lack of prospective proof to-date, and when a thymectomy is performed
      a total resection is indicated.

PMID- 12808371
TI  - The emergency management of headaches.
AB  - BACKGROUND: Sufferers of severe headaches present for emergent treatment when
      attacks are unusually severe or refractory to therapy. Secondary headaches must
      always be considered. REVIEW SUMMARY: Most severe attacks are due to migraine,
      but cluster headaches may present for emergent treatment as well. It is unusual
      for a tension-type headache to be severe, unless it is associated with migraine.
      Options for emergent treatment of migraine depend upon which treatments have been
      recently utilized and what associated symptoms are present. CONCLUSIONS: Options
      include neuroleptics, triptans, nonsteroidal antiinflammatory agents, ergots, and
      intravenous valproic acid. Cluster headaches are best managed with oxygen
      inhalation, injectable sumatriptan, or dihydroergotamine.

PMID- 12808373
TI  - Neurological evaluation of urinary incontinence in the female patient.
AB  - BACKGROUND: Urinary incontinence is one of the most common medical complaints of
      women older than 50 years of age. Understanding the anatomy and physiology is
      important in the diagnosis and management of these patients. REVIEW SUMMARY:
      Evaluation of the incontinent patient is complicated by the frequent vagueness of
      the patient's complaints, complexity of anatomic pathways involved in maintaining
      continence, and the poor availability of specific diagnostic tests for evaluating
      incontinence. Close attention to specific aspects of the patient's history
      including type of leakage, precipitating factors, and associated symptoms can
      dramatically increase diagnostic yield. In addition to the routine neurologic
      examination, certain additional clinical testing sheds light on the site of
      lesion causing incontinence. Examination of tone and voluntary contraction of the
      anal sphincter, bulbocavernosus reflex, and the anal reflex are valuable but
      underused methods that can be cost-effective as a means of achieving a specific
      diagnosis. Electrophysiological testing may be needed as an adjunct to physical
      examination and includes electromyography of the anal sphincter and urodynamic
      testing. CONCLUSIONS: Urinary incontinence is a problem that needs a systematic
      approach to the patient both in terms of specific questions and physical
      examination. This allows categorization of type of urinary incontinence and
      identification of the anatomic process. During treatment the underlying
      neurologic problem causing incontinence needs to be addressed. Mild incontinence
      may be treated by conservative measures that reduce social inconvenience. In
      patients for whom the problem is more severe, various pharmacologic and surgical
      options are available.

PMID- 12808372
TI  - Childhood autism: a circuit syndrome?
AB  - BACKGROUND: Autism is a disorder that can lead to life-long disability.
      Currently, the etiology of autism is unknown, and although there are treatments
      for some of the behavioral abnormalities, there is no cure. REVIEW SUMMARY: While
      this article will review the clinical, anatomic, and pathologic features seen in
      autism, the primary focus will be to present a new and provocative unifying
      theory regarding the underlying mechanisms causing this disorder. Current
      research advances, some controversial, will be discussed, and a novel definition
      of autism as a "circuit syndrome" will be presented. The work elaborated here
      will tie many of the disparate findings together, based on the idea that autism
      arises from abnormalities of the cerebellolimbic circuitry. Some of the more
      alternative theories of autism, such as mercury toxicity, linkage to the measles,
      mumps, and rubella vaccine, and the use of secretin will be discussed. Finally,
      pharmacologic treatment options will be reviewed. CONCLUSIONS: Autism is not
      single disorder but represents dysfunction of the cerebellolimbic circuitry that
      can arise from many different etiologies.

PMID- 12808374
TI  - Patient family fact sheet. Dystonia.

PMID- 12808376
TI  - Advances in human stem cell research.

PMID- 12808377
TI  - Blastocyst transfer.

PMID- 12808378
TI  - Ovarian folliculogenesis: emerging role of in vitro maturation of oocytes and
      follicles in clinical practice.

PMID- 12808379
TI  - GnRH antagonists.

PMID- 12808380
TI  - Molecular and clinical evidence for the unique nature of individual selective
      estrogen receptor modulators.

PMID- 12808381
TI  - Recombinant gonadotropins.

PMID- 12808382
TI  - Low-dose hormone therapy for postmenopausal women.

PMID- 12808383
TI  - Insulin sensitizers for polycystic ovary syndrome.

PMID- 12808384
TI  - Anti-osteoporotic medications: traditional and nontraditional.

PMID- 12808386
TI  - Associated multiple gestation--ART.

PMID- 12808385
TI  - Dopamine agonist therapy for hyperprolactinemia.

PMID- 12808388
TI  - Physiologic aspects of exercise in pregnancy.

PMID- 12808389
TI  - Nutrition during pregnancy for the physically active woman.

PMID- 12808390
TI  - Athletes and pregnancy.

PMID- 12808391
TI  - Recent studies in the epidemiologic assessment of physical activity, fetal
      growth, and preterm delivery: a narrative review.

PMID- 12808392
TI  - Effect of exercise on birthweight.

PMID- 12808393
TI  - Exercise in water during pregnancy.

PMID- 12808394
TI  - Thermoregulation during exercise in pregnancy.

PMID- 12808395
TI  - Orthopedic considerations during pregnancy.

PMID- 12808396
TI  - Substrate utilization and hormonal responses to exercise in pregnancy.

PMID- 12808397
TI  - Exercise: the alternative therapeutic intervention for gestational diabetes.

PMID- 12808398
TI  - Canadian guidelines for exercise in pregnancy.

PMID- 12808399
TI  - Exercise during pregnancy and the postpartum period.
AB  - The physiologic and morphologic changes of pregnancy may interfere with the
      ability to engage safely in some forms of physical activity. A woman's overall
      health, including obstetric and medical risks, should be evaluated before
      prescribing an exercise program. Generally, participation in a wide range of
      recreational activities appears to be safe during pregnancy; however, each sport
      should be reviewed individually for its potential risk, and activities with a
      high risk of falling or those with a high risk of abdominal trauma should be
      avoided during pregnancy. Scuba diving also should be avoided throughout
      pregnancy because the fetus is at an increased risk for decompression sickness
      during this activity. In the absence of either medical or obstetric
      complications, 30 minutes or more of moderate exercise a day on most, if not all,
      days of the week is recommended for pregnant women.

PMID- 12808400
TI  - Issues and impacts of the changing nature of scientific communication.

PMID- 12808401
TI  - Management of filamentary keratitis associated with aqueous-deficient dry eye.
AB  - PURPOSE: To review the incidence, underlying pathophysiology, and clinical
      features of filamentary keratitis and to identify evidence-based best-practice
      strategies for managing filamentary keratitis. METHODS: A comprehensive review of
      published literature was undertaken. Recommendations for best-practice management
      strategies were based on the available evidence. Three cases are presented to
      illustrate the clinical findings and management of patients with chronic
      filamentary keratitis. RESULTS: Although the evidence base is limited by the
      absence of well-designed studies, current evidence indicates the following: (1)
      Aqueous-deficient dry eye (keratoconjunctivitis sicca) is the most common ocular
      condition associated with filamentary keratitis. (2) Current best-practice
      management of filamentary keratitis involves treating the underlying dry eye and
      specific treatments for the corneal filaments. Proposed treatments include
      nonpreserved lubricants, topical steroidal and nonsteroidal anti-inflammatory
      agents, and punctal plugs for aqueous-deficient dry eye as well as mechanical
      removal of filaments, hypertonic saline, mucolytic agents, and bandage contact
      lenses for the filaments. (3) Filamentary keratitis can be induced or exacerbated
      by contact lens wear and ocular surgical procedures such as cataract surgery and
      corneal graft surgery. Pre- and postoperative ocular surface management
      strategies should be considered in the surgical planning of patients with, or who
      are susceptible to, filamentary keratitis. Filamentary keratitis can also be
      induced and/or exacerbated by chronic use of ocular and/or systemic medications,
      and alternate medications or additional measures to manage the tear film and
      ocular surface may be required in these cases. CONCLUSIONS: Filamentary keratitis
      can be a chronic, recurrent, and debilitating condition. With a systemic approach
      to diagnosis and management, the condition can be effectively controlled and the
      incidence and severity of recurrences minimized.

PMID- 12808402
TI  - Normative data for the Rosner Test of Visual Analysis Skills on an Australian
      population.
AB  - PURPOSE: The purpose of this study was to produce normative data for Rosner's
      Test of Visual Analysis Skills (TVAS, 1979). METHODS: A total of 881 unselected
      children aged 5 to 10 years and in the first 4 years of school in Australia were
      tested to threshold on the TVAS. Percentile, mean, and standard deviation for
      each age group were calculated. RESULTS: We found a steady increase in scores
      with grade and age and a significant difference in scores between most of the
      ages and grades. This progression indicates that the test accurately reflects
      increased sophistication in visual analysis skills. There was no significant
      difference between girls and boys. CONCLUSIONS: Normative data is presented in
      terms of percentiles for each age group. Interpretation of the scores is
      discussed.

PMID- 12808403
TI  - Measuring central corneal thickness with ultrasound pachymetry.
AB  - PURPOSE: To determine how many ultrasound pachymetry measurements are required to
      obtain a reasonable estimate of central corneal thickness. METHODS: Five central
      corneal thickness measurements were obtained from each eye of 101 patients with
      normal corneas. The means of fewer than five readings were compared with the mean
      of five values for each eye to determine the incremental clinical value of
      additional measurements. RESULTS: Compared with the mean of five values, fewer
      than three measurements per eye provided a mean central corneal thickness value
      with inadequate confidence. Conversely, means of more than three readings
      provided little additional confidence over means of three values. CONCLUSIONS:
      Central corneal thickness by ultrasound pachymetry can be adequately assessed in
      the majority of eyes by taking three measurements per eye.

PMID- 12808404
TI  - Changes in corneal structure with continuous wear of high-Dk soft contact lenses:
      a pilot study.
AB  - PURPOSE: Despite numerous studies that have considered the effects of extended
      wear of high-Dk soft contact lenses on ocular physiology, little attention has
      been paid to the impact of such lenses on central or peripheral corneal thickness
      and curvature. The present study aims to report the time course of changes in
      corneal thickness and curvature that accompanies the 30-night continuous wear of
      new silicone hydrogel soft contact lenses in a neophyte population in a
      longitudinal study. METHODS: Six subjects wore high-Dk lotrafilcon (Dk = 140) on
      a 30-night replacement schedule for 12 months. Only measurements from the right
      eye were considered for analysis. Topographical measurements of corneal thickness
      and curvature were taken. The same parameters were monitored for an additional
      period of 3 months after lens removal. RESULTS: An almost homogenous increase in
      corneal radius of curvature was detected for all the locations studied, being
      statistically significant for the 4-mm cord diameter area. This effect was
      associated with a progressive thinning effect for the central cornea, whereas
      midperipheral and peripheral areas did not display such a thinning effect during
      continuous wear. These effects were still evident for the central cornea 3 months
      after contact lens wear discontinuation. CONCLUSIONS: Continuous wear of high-Dk
      silicone hydrogel contact lenses is associated with clinically appreciable
      changes in topographical corneal curvature, whereas only a reduction in corneal
      thickness is appreciated in the central area. This effect seems to be a result of
      mechanical pressure induced by these hybrid hyperpermeable materials,
      characterized by a higher modulus of elasticity. The small sample size
      compromises the conclusions addressed from this study, and further work will be
      necessary to confirm the present results.

PMID- 12808405
TI  - The reliability and validity of hand-held refractometry water content measures of
      hydrogel lenses.
AB  - PURPOSE: To investigate within- and between-examiner reliability and validity of
      hand-held refractometry water content measures of hydrogel lenses. METHODS:
      Nineteen lenses of various nominal water contents were examined by two examiners
      on two occasions separated by 1 hour. An Atago N2 hand-held refractometer was
      used for all water content measures. Lenses were presented in a random order to
      each examiner by a third party, and examiners were masked to any potential lens
      identifiers. Intraclass correlation coefficients (ICC), 95% limits of agreement,
      and Wilcoxon signed rank test were used to characterize the within- and between
      examiner reliability and validity of lens water content measures. RESULTS: Within
      examiner reliability was excellent (ICC, 0.97; 95% limits of agreement, -3.6% to
      +5.7%), and the inter-visit mean difference of 1.1 +/- 2.4% was not biased (p =
      0.08). Between-examiner reliability was also excellent (ICC, 0.98; 95% limits of
      agreement, -4.1% to +3.9%). The mean difference between examiners was -0.1 +/-
      2.1% (p = 0.83). The mean difference between the nominally reported water content
      and our water content measures was -2.1 +/- 1.7% (p < 0.001); the 95% limits of
      agreement for this difference were -5.4% to +1.1%. CONCLUSION: There is good
      reliability within and between examiners in measuring water content of hydrogel
      lenses. However, with our sample of lenses, examiners tended to overestimate the
      nominal water content of hydrogel lenses. As discussed, this bias may be
      associated with the Brix scale used in refractometry and is material dependent.
      Therefore, investigators may need to account for bias when measuring hydrogel
      lens water content via hand-held refractometry.

PMID- 12808406
TI  - Vertical cup-to-disc ratio: agreement between direct ophthalmoscopic estimation,
      fundus biomicroscopic estimation, and scanning laser ophthalmoscopic measurement.
AB  - PURPOSE: Ophthalmoscopic estimation of the vertical cup-to-disc ratio (VCDR) of
      the optic nerve head is important in the management of patients with glaucoma or
      who are glaucoma suspects. The purpose of this study was to compare the accuracy
      of estimation of VCDR obtained with direct ophthalmoscopy with that obtained with
      fundus biomicroscopy through undilated pupils. Measurements of VCDR obtained with
      the Heidelberg Retina Tomograph (HRT), a confocal scanning laser ophthalmoscope,
      were used as a standard. METHODS: Thirty young, healthy adults had their optic
      discs photographed and then imaged and analyzed with the HRT. Due to HRT software
      limitations, the VCDR could not be calculated automatically, and so a validated
      VCDR measurement was derived. This was used as the standard against which
      ophthalmoscopic estimations were compared. Two months later, the subjects had
      their VCDRs estimated using direct ophthalmoscopy and fundus biomicroscopy
      performed in random order after varying time intervals. Agreement between
      ophthalmoscopic VCDR estimation and HRT-derived VCDR measurement was assessed by
      means of bias plots and the weighted kappa statistic. RESULTS: Compared with the
      HRT-derived VCDR measurement, both ophthalmoscopic techniques tended to
      underestimate VCDR. The bias with direct ophthalmoscopy was statistically
      significant. There were also wide variations in VCDR estimation with direct
      ophthalmoscopy and fundus biomicroscopy, which were more pronounced with direct
      ophthalmoscopy. The weighted kappa statistic indicated moderate agreement between
      fundus biomicroscopy and HRT-derived VCDR measurement. There was poor to fair
      agreement between direct ophthalmoscopy and HRT-derived VCDR measurement. The
      level of disagreement was independent of HRT-derived VCDR, optic nerve head size
      and pupil size for both direct ophthalmoscopy and fundus biomicroscopy.
      CONCLUSIONS: Fundus biomicroscopy enables more accurate, less variable VCDR
      estimation than direct ophthalmoscopy. The clinician should record which method
      they used to examine the optic nerve head so that subsequent clinical decisions
      are not influenced by apparent VCDR changes.

PMID- 12808407
TI  - Effect of exercise on intraocular pressure and pulsatile ocular blood flow in a
      young normal population.
AB  - PURPOSE: The hypotensive effect of exercise on intraocular pressure is well
      documented, however, little is known about the effect of exercise on pulsatile
      ocular blood flow. This study examines this effect and follows the recovery of
      intraocular pressure and pulsatile ocular blood flow after a standard exercise
      period. METHODS: Eighteen visually normal subjects participated in a 4-min period
      of bicycle ergometry. Intraocular pressure and pulsatile ocular blood flow were
      measured by pneumotonometry before, immediately after exercise, and at regular
      intervals during the recovery period. RESULTS: Intraocular pressure was found to
      decrease significantly with strenuous exercise and recovered gradually toward
      baseline over a period of 30 min. Pulsatile ocular blood flow increased
      significantly immediately after exercise then returned to baseline levels between
      5 and 10 min after stopping exercise. CONCLUSIONS: This study confirms the
      hypotensive effect of exercise on intraocular pressure and shows that exercise
      significantly increases pulsatile ocular blood flow.

PMID- 12808408
TI  - Accommodation and vergence require effort-to-see.
AB  - PURPOSE: Accommodation and vergence both appear to be influenced by multiple
      nonsensory factors. "Effort-to-see" is one of these factors. This study was
      designed to assess the extent to which effort-to-see affects accommodation and
      vergence. METHOD: Nine volunteers participated in this study. Stimuli were chosen
      to stimulate selectively either accommodation or vergence. Accommodation and
      vergence responses were measured while observers viewed each stimulus with the
      instruction of "concentrate" or "space-out." RESULTS: Both oculomotor adjustments
      were accurate when observers "concentrated," but regressed toward the resting
      posture during identical stimulus conditions when observers spaced-out.
      Interesting, individual differences in oculomotor behavior were apparent.
      CONCLUSION: This study demonstrates that higher-level attentional factors play an
      important role in accommodation and vergence for active exploration of the three
      dimensional environment.

PMID- 12808409
TI  - The role of cerebrovascular disease in dementia.
AB  - BACKGROUND: Improvements in health care over the last 50 years have lengthened
      average life expectancy significantly, resulting in considerable growth of the
      population over 65 years of age. With increased age, however, comes an increased
      risk for Alzheimer's disease (AD), and the prevalence of AD is predicted to reach
      epidemic proportions by the later half of the 21st century. The prevalence of
      cerebrovascular disease also increases with age, and recent evidence suggests
      that cerebrovascular risk factors such as hypertension and hypercholesterolemia
      also increase an individual's risk for AD, suggesting a potential interaction
      between these two very common disorders. The potential impact of cerebrovascular
      disease on general cognitive health is not yet well understood, but is now being
      actively explored and clarified. REVIEW SUMMARY: Cerebrovascular disease may
      manifest itself in many ways, and this review begins by discussing the possible
      spectrum of brain injury associated with common cerebrovascular risk factors. The
      prominent role of brain imaging to detect clinically silent cerebrovascular
      disease is recognized and reviewed. The neuropsychological consequences of
      cerebrovascular disease across the cognitive spectrum is also reviewed, including
      potential mechanisms by which cerebrovascular disease may interact with AD to
      increase the expression or hasten the progression of dementia. CONCLUSIONS:
      Cerebrovascular risk factors, common to the elderly, lead to pernicious brain
      injury and subtle cognitive impairment that most probably places the individual
      at greater lifetime risk for dementia. The cause of dementia among individuals
      with cerebrovascular disease, however, remains AD. Recognition of the potential
      role of cerebrovascular disease as an independent risk factor for AD offers the
      possibility of primary prevention through treatment of well-recognized risk
      factors and deserves further study. In the meantime, clinicians presented with an
      individual suffering from a slowly progressive dementia and findings of
      clinically silent cerebrovascular brain injury should recognize the potential
      role of cerebrovascular disease in the dementia process but not ignore the likely
      overwhelming effects of AD and treat appropriately.

PMID- 12808410
TI  - Acupuncture in clinical neurology.
AB  - BACKGROUND: A majority of people in the United States use alternative or
      complementary therapy at some point in their lives, and acupuncture is among the
      most frequently used modalities. Many United States medical schools offer courses
      in alternative medicine, and a growing number of insurers offer coverage for
      alternative therapies. This paper critically reviews our current knowledge about
      the safety and efficacy of acupuncture for neurologic conditions. REVIEW SUMMARY:
      Acupuncture is a safe procedure when performed by trained professionals.
      Complications from acupuncture are rare and mainly related to negligence of
      sterile technique. Studies of the therapeutic value of acupuncture are fraught
      with challenging methodologic problems, including the choice of a placebo, a
      suitable control treatment, and the technique of stimulation applied. Clinical
      trials of the use of acupuncture for pain syndromes (headache, neck, and back
      pain), stroke rehabilitation, Parkinson's disease, multiple sclerosis, and
      substance abuse are reviewed. CONCLUSIONS: Based on the current literature, no
      definitive recommendation can be made regarding the efficacy of acupuncture for
      common pain syndromes including headache, and neck and back pain. Better quality
      clinical trials fail to demonstrate efficacy for the use of acupuncture as part
      of a rehabilitation program following stroke or as a treatment for drug
      addiction. Acupuncture may have a role in the treatment of sleep disturbance
      associated with Parkinson's disease but was not efficacious for the primary
      symptoms of either Parkinson's disease or multiple sclerosis. In light of
      increasing public interest and use of alternative therapies, this review may be
      helpful in promoting more discussion between patients and physicians about the
      use of acupuncture.

PMID- 12808411
TI  - Information technology, the internet, and the future of neurology.
AB  - BACKGROUND: This review addresses the impact of information technology and the
      Internet on the current and future practice of neurology. Information technology
      is influencing medical practice in ways that could be both beneficial and
      harmful. Scenarios are presented to depict some of the ways in which the practice
      of neurology is being influenced by the growth of technology. REVIEW SUMMARY:
      First, the advantages and disadvantages of e-mail as a means of doctor-patient
      communication are presented. Some of the ethical and legal issues arising in this
      context are discussed.Second, the Internet is changing neurologists'
      relationships to other professionals in the health care industry. Geographical
      isolation is less problematic than in the past. Telemedicine, including remote
      consulting via the Web, has special implications for neurologists in several
      areas, including stroke management, movement disorders, and epilepsy.Third, the
      growing availability of large databases, powerful search engines, and online full
      text journals is discussed. Skill in navigating and managing these resources will
      become increasingly important. New computer-assisted decision support systems
      will continue to be implemented. Applications exist or are being developed for
      use by clinicians for many specific neurologic disorders.Finally, some of the
      problematic issues concerning medical use of the Internet are discussed,
      including availability, portability, security, quality, and outcomes.
      CONCLUSIONS: Medical information systems, with their attendant advantages and
      limitations, will become increasingly significant in the practice of neurology.
      Despite overall improvement in access to information, major barriers still exist
      to the proper implementation and utilization of truly integrated information
      systems.

PMID- 12808412
TI  - Observations on the use of vagus nerve stimulation earlier in the course of
      pharmacoresistant epilepsy: patients with seizures for six years or less.
AB  - BACKGROUND: This study retrospectively compared the effectiveness of vagus nerve
      stimulation (VNS) therapy among a constant cohort of patients in the patient
      outcome registry, which systematically monitors outcomes of patients receiving
      VNS therapy. Patients in the study had pharmacoresistant seizures for 6 years or
      less (early treatment group) or more than 6 years (late treatment group) before
      initiation of VNS therapy, and results are provided after both 3 and 12 months.
      REVIEW SUMMARY: Of 405 patients, 51 were in the early and 354 in the late
      treatment groups. Median age at onset of seizures was 7 years in the early and
      4.5 years in the late treatment group. Seizure reduction of 100% was reported in
      7.8% (early) and 3.7% (late) patients at 3 months and 11.8% (early) and 4.5%
      (late) at 12 months (P = 0.033). Reductions in seizure frequency greater than or
      equal to 90% for early and late treatment groups were similar: 11.8% (early) and
      11.0% (late) at 3 months and 23.5% (early) and 17.0% (late) at 12 months.
      CONCLUSIONS: Patients treated earlier with VNS therapy were twice as likely to
      report no seizures as patients who had seizures for more than 6 years before they
      received VNS therapy. The effectiveness of VNS therapy should be assessed among
      other patients with pharmacoresistant seizures and lesser cumulative seizure
      loads.

PMID- 12808413
TI  - Chorea in an octogenarian.

PMID- 12808414
TI  - 10 most commonly asked questions about carotid artery occlusion.

PMID- 12808415
TI  - Patient and family fact sheet. The electromyogram.

PMID- 12808418
TI  - Insulin therapy in type 2 diabetes.

PMID- 12808422
TI  - Fear and the cerebellum.

PMID- 12808423
TI  - What's new in epilepsy genetics?

PMID- 12808424
TI  - Association between cannabinoid receptor gene (CNR1) and childhood attention
      deficit/hyperactivity disorder in Spanish male alcoholic patients.

PMID- 12808425
TI  - Two-step association analyses of the chromosome 18p11.2 region in schizophrenia
      detect a locus encompassing C18orf1.

PMID- 12808426
TI  - Hypothalamic-pituitary-adrenal (HPA) system activity in depression and infection
      with Borna disease virus and Chlamydia pneumoniae.

PMID- 12808427
TI  - Genetic polymorphisms and personality in healthy adults: a systematic review and
      meta-analysis.
AB  - A meta-analysis was conducted on studies reporting data on associations between
      candidate genes and human personality. Studies reporting data for psychiatric
      populations (including organic disease and substance abuse) were excluded. A
      total of 46 studies contributed to the analysis. Pooled data using a fixed
      effects model suggested significant associations between the 5HTT LPR, DRD4 c>t,
      DRD4 length, DRD2 A1/A2, DRD3 A1/A2 polymorphisms and personality traits. A
      multivariate analysis using a mixed-effects model and including age, sex and
      predominant ethnicity as covariates was applied to the analyses of 5HTT LPR and
      DRD4 length polymorphism data. Only the association between the 5HTT LPR
      polymorphism and avoidance traits remained significant (P=0.038). However,
      sensitivity analyses excluding data from studies reporting allele frequencies not
      in Hardy-Weinberg equilibrium and unpublished data resulted in this association
      no longer being significant. Implications for the design of future association
      studies of human personality are discussed, including the likely sample sizes
      that will be required to achieve sufficient power and the potential role of
      moderating variables such as sex.

PMID- 12808428
TI  - Support for genetic variation in neuregulin 1 and susceptibility to
      schizophrenia.
AB  - Recently, it has been reported that genetic variants around the gene neuregulin 1
      are associated with schizophrenia in an Icelandic sample. Of particular interest
      was the presence of a single-risk haplotype that was significantly over
      represented in schizophrenic individuals compared to controls (15.4 : 7.5%, P=6.7
      x 10(-6)). We have attempted to replicate this result in our large collection of
      573 schizophrenia cases and 618 controls. We found that the risk haplotype was
      more common in cases than controls (9.5 : 7.5%; P=0.04), and especially in our
      subset of 141 cases with a family history of schizophrenia (11.6%; P=0.019). Our
      results therefore replicate the Icelandic findings in an out-bred Northern
      European population, although they suggest that the risk conferred by the
      haplotype is small.

PMID- 12808429
TI  - Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to
      chromosome 6q23 and supports a locus at chromosome 10q24.
AB  - Schizophrenia is a complex neuropsychiatric disorder to which an as-yet-unknown
      number of genes contribute, interacting with each other and the environment.
      Linkage analyses have implicated several chromosomal regions as harboring
      schizophrenia susceptibility loci although rarely at levels commensurate with
      proposed thresholds for genome-wide significance. We systematically recruited
      Arab Israeli families multiply affected with schizophrenia from the catchment
      area of a Regional Mental Health Center. Clinical diagnoses were established by
      semistructured interviews and all other available sources of information under
      narrow, core and broad categories. Using 350 microsatellite markers, spaced at an
      average of 10.3 cM, we performed an autosomal scan in 155 subjects from 21
      families. Linkage analysis employed affects only, multipoint, nonparametric
      (model-free) and also parametric (dominant and recessive) approaches. We detected
      significant evidence for a schizophrenia susceptibility gene at chromosome 6q23
      with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) under the broad
      diagnostic category and a parametric LOD score of 3.33 (dominant model). Under
      the core diagnostic category the NPL was 4.29 (P=0.00001) and the LOD score 4.16
      (dominant model). We also detected suggestive evidence for linkage at chromosome
      10q24 under the broad diagnostic category (NPL 3.24, P=0.0008; heterogeneity LOD
      score, dominant model 2.65, alpha=0.82). Additionally, NPL scores >2.0 were
      observed at chromosome 2q37, 4p15-16, 7p22, 9q21-22 and 14q11.1-11.2. The linkage
      we detected at chromosome 6q23 fulfills the criteria for genome-wide significance
      and is located approximately midway between loci suggested by a previous
      significant report at chromosome 6q25 and findings located more centromerically
      at 6q21-22.

PMID- 12808430
TI  - Identification of a high-risk haplotype for the dystrobrevin binding protein 1
      (DTNBP1) gene in the Irish study of high-density schizophrenia families.
AB  - A recent report showed significant associations between several SNPs in a
      previously unknown EST cluster with schizophrenia. (1). The cluster was
      identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence
      database comparisons and homology with mouse DTNBP1. (2). However, the linkage
      disequilibrium (LD) among the SNPs in DTNBP1 as well as the pattern of
      significant SNP-schizophrenia association was complex. This raised several
      questions such as the number of susceptibility alleles that may be involved and
      the size of the region where the actual disease mutation(s) could be located. To
      address these questions, we performed different single-marker tests on the 12
      previously studied and 2 new SNPs in DTNBP1 that were re-scored using an improved
      procedure, and performed a variety of haplotype analyses. The sample consisted of
      268 Irish multiplex families selected for high density of schizophrenia. Results
      suggested a simple structure where the LD in the target region could be explained
      by 6 haplotypes that together accounted for 96% of haplotype diversity in the
      whole sample. From these six, a single high-risk haplotype was identified that
      showed a significant association with schizophrenia and explained the pattern of
      significant findings in the analyses with individual markers. This haplotype was
      30 kb long, had a large effect, could be measured with two tag SNPs only, had a
      frequency of 6% in our sample, seemed to be of relatively recent origin in
      evolutionary terms, and was equally distributed over Ireland. Implications of
      these findings for follow-up and replication studies are discussed.

PMID- 12808431
TI  - Linkage analysis of candidate regions using a composite neurocognitive phenotype
      correlated with schizophrenia.
AB  - As schizophrenia is genetically and clinically heterogeneous, systematic
      investigations are required to determine whether ICD-10 or DSM-IV categorical
      diagnoses identify a phenotype suitable and sufficient for genetic research, or
      whether correlated phenotypes incorporating neurocognitive performance and
      personality traits provide a phenotypic characterisation that accounts better for
      the underlying variation. We utilised a grade of membership (GoM) model (a
      mathematical typology developed for studies of complex biological systems) to
      integrate multiple cognitive and personality measurements into a limited number
      of composite graded traits (latent pure types) in a sample of 61 nuclear families
      comprising 80 subjects with ICD-10/DSM-IV schizophrenia or schizophrenia spectrum
      disorders and 138 nonpsychotic first-degree relatives. GoM probability scores,
      computed for all subjects, allowed individuals to be partly assigned to more than
      one pure type. Two distinct and contrasting neurocognitive phenotypes, one
      familial, associated with paranoid schizophrenia, and one sporadic, associated
      with nonparanoid schizophrenia, accounted for 74% of the affected subjects.
      Combining clinical diagnosis with GoM scores to stratify the entire sample into
      liability classes, and using variance component analysis (SOLAR), in addition to
      parametric and nonparametric multipoint linkage analysis, we explored candidate
      regions on chromosomes 6, 10 and 22. The results indicated suggestive linkage for
      the familial neurocognitive phenotype (multipoint MLS 2.6 under a low-penetrance
      model and MLS>3.0 under a high-penetrance model) to a 14 cM area on chromosome 6,
      including the entire HLA region. Results for chromosomes 10 and 22 were negative.
      The findings suggest that the familial neurocognitive phenotype may be a
      pleiotropic expression of genes underlying the susceptibility to paranoid
      schizophrenia. We conclude that use of composite neurocognitive and personality
      trait measurements as correlated phenotypes supplementing clinical diagnosis can
      help stratify the liability to schizophrenia across all members of families prior
      to linkage, allow the search for susceptibility genes to focus selectively on
      subsets of families at high genetic risk, and augment considerably the power of
      genetic analysis.

PMID- 12808432
TI  - Novel truncated isoform of SK3 potassium channel is a potent dominant-negative
      regulator of SK currents: implications in schizophrenia.
AB  - The small-conductance calcium-activated K(+) channel SK3 (SKCa3/KCNN3) regulates
      electrical excitability and neurotransmitter release in monoaminergic neurons,
      and has been implicated in schizophrenia, ataxia and anorexia nervosa. We have
      identified a novel SK3 transcript, SK3-1B that utilizes an alternative first exon
      (exon 1B), but is otherwise identical to SK3. SK3-1B, mRNA is widely distributed
      in human tissues and is present at 20-60% of SK3 in the brain. The SK3-1B protein
      lacks the N-terminus and first transmembrane segment, and begins eight residues
      upstream of the second transmembrane segment. When expressed alone, SK3-1B did
      not produce functional channels, but selectively suppressed endogenous SK3
      currents in the pheochromocytoma cell line, PC12, in a dominant-negative fashion.
      This dominant inhibitory effect extended to other members of the SK subfamily,
      but not to voltage-gated K(+) channels, and appears to be due to intracellular
      trapping of endogenous SK channels. The effect of SK3-1B expression is very
      similar to that produced by expression of the rare SK3 truncation allele, SK3
      Delta, found in a patient with schizophrenia. Regulation of SK3 and SK3-1B levels
      may provide a potent mechanism to titrate neuronal firing rates and
      neurotransmitter release in monoaminergic neurons, and alterations in the
      relative abundance of these proteins could contribute to abnormal neuronal
      excitability, and to the pathogenesis of schizophrenia.

PMID- 12808433
TI  - High prevalence of rare dopamine receptor D4 alleles in children diagnosed with
      attention-deficit hyperactivity disorder.
AB  - Associations have been reported of the 7-repeat (7R) allele of the human dopamine
      receptor D4 (DRD4) gene with both the personality trait of novelty seeking and
      attention-deficit/hyperactivity disorder (ADHD). The increased prevalence of the
      7R allele in ADHD probands is consistent with the common variant-common disorder
      hypothesis, which proposes that the high frequency of many complex genetic
      disorders is related to common DNA variants. Recently, based on the unusual DNA
      sequence organization and strong linkage disequilibrium surrounding the DRD4 7R
      allele, we proposed that this allele originated as a rare mutational event, which
      nevertheless increased to high prevalence in human populations by positive
      selection. We have now determined, by DNA resequencing of 250 DRD4 alleles
      obtained from 132 ADHD probands, that most ADHD 7R alleles are of the conserved
      haplotype found in our previous 600 allele worldwide DNA sample. Interestingly,
      however, half of the 24 haplotypes uncovered in ADHD probands were novel (not one
      of the 56 haplotypes found in our prior population studies). Over 10 percent of
      the ADHD probands had these novel haplotypes, most of which were 7R allele
      derived. The probability that this high incidence of novel alleles occurred by
      chance in our ADHD sample is much less than 0.0001. These results suggest that
      allelic heterogeneity at the DRD4 locus may also contribute to the observed
      association with ADHD.

PMID- 12808434
TI  - Evidence that a single nucleotide polymorphism in the promoter of the G protein
      receptor kinase 3 gene is associated with bipolar disorder.
AB  - In a genome-wide linkage survey, we have previously shown evidence suggesting
      that the chromosome 22q12 region contains a susceptibility locus for bipolar
      disorder (BPD). Two independent family sets yielded lod scores suggestive of
      linkage at markers in this region near the gene G protein receptor kinase 3
      (GRK3). GRK3 is an excellent candidate risk gene for BPD since GRK3 is expressed
      widely in the brain, and since GRKs play key roles in the homologous
      desensitization of G protein-coupled receptor signaling. We have also previously
      shown GRK3 expression to be induced by amphetamine in an animal model of mania
      using microarray-based expression profiling. To identify possible functional
      mutations in GRK3, we sequenced the putative promoter region, all 21 exons, and
      intronic sequence flanking each exon, in 14-22 individuals with BPD. We found six
      sequence variants in the 5'-UTR/promoter region, but no coding or obvious splice
      variants. Transmission disequilibrium analyses of one set of 153 families
      indicated that two of the 5'-UTR/promoter variants are associated with BPD in
      families of northern European Caucasian ancestry. A supportive trend towards
      association to one of these two variants (P-5) was then subsequently obtained in
      an independent sample of 237 families. In the combined sample, the P-5 variant
      had an estimated allele frequency of 3% in bipolar subjects, and displayed a
      transmission to non-transmission ratio of 26 : 7.7 (chi(2)=9.6, one-sided P
      value=0.0019). Altogether, these data support the hypothesis that a dysregulation
      in GRK3 expression alters signaling desensitization, and thereby predisposes to
      the development of BPD.

PMID- 12808435
TI  - Linkage of a bipolar disorder susceptibility locus to human chromosome 13q32 in a
      new pedigree series.
AB  - Bipolar (BP) disorder or manic depressive illness is a major psychiatric disorder
      for which numerous family, twin and adoption studies support a substantial
      genetic contribution. Recently, we reported the results of a genome-wide search
      for BP disorder susceptibility loci in 20 pedigrees. Suggestive evidence for
      linkage was found in this study at three markers on 13q, representing possibly
      two peaks separated by 18 cM. We have now collected a second set of 32 pedigrees
      segregating BP disorder and have tested for evidence of linkage to markers on
      human chromosome 13q. In this sample, we have replicated the linkage result in
      13q32 at D13S154 (lod=2.29), the more proximal of the two original peaks. When
      all 52 pedigrees were combined, the multipoint maximum lod score peaked
      approximately 7 cM proximal to D13S154 (lod=3.40), with a second peak occurring
      between D13S225 and D13S796 (lod=2.58). There have been several other reports of
      significant linkage to both BP disorder and schizophrenia in this region of
      chromosome 13. These pedigrees provide additional evidence for at least one locus
      for BP disorder in 13q32, and are consistent with other reports of a possible
      genetic overlap between these disorders.

PMID- 12808437
TI  - Pancreatic cancer escape variants that evade immunogene therapy through loss of
      sensitivity to IFNgamma-induced apoptosis.
AB  - Combined injections into experimental tumor nodules of adenovirus encoding IL-12
      and certain chemokines are capable to induce immune-mediated complete
      regressions. In this study, we found that the combination of two adenoviruses,
      one encoding IL-12 and other MIP3alpha (AdCMVIL-12+AdCMVMIP3alpha) was very
      successful in treating CT-26-derived colon carcinomas. However, in experimental
      tumors generated from the pancreatic carcinoma cell line Panc02 such combined
      treatment induces 50% of macroscopic complete regressions, although local
      relapses within 1 week are almost constant. We derived cell lines from such
      relapsing tumors and found that experimental malignancies derived from their
      inoculum were not amenable to treatment in any case with AdCMVIL-12+AdCMVMIP
      3alpha. Importantly, relapsing cell lines were insensitive to in vitro induction
      of apoptosis by IFNgamma, in clear contrast with the original Panc02 cells.
      Comparative analyses by cDNA arrays of relapsing cell lines versus wild-type
      Panc02 were performed revealing an important number of genes (383) whose
      expression levels were modified more than two-fold. These changes grouped in
      certain gene ontology categories should harbor the mechanistic explanations of
      the acquired selective resistance to IFNgamma.

PMID- 12808438
TI  - Tissue-dependent factors affect gene delivery to tumors in vivo.
AB  - Systemic application of surface-shielded transferrin-polyethylenimine/DNA
      complexes leads to predominant DNA uptake and gene expression in Neuro2a tumors
      in syngeneic A/J mice. Similarly, high expression levels were found in Huh-7 and
      HepG2 human tumor xenografts in SCID mice after systemic application of surface
      shielded EGF-PEG-PEI/DNA complexes. Significant DNA uptake but low gene
      expression were found in the M-3 melanoma while no DNA uptake and no gene
      expression were found in KB, 518A2, A549, and SW480 xenograft tumor models. To
      elucidate the reasons for these differences, the tumors were analyzed for
      vascularization and infiltration of macrophages. Neuro2a, Huh-7, and HepG2 tumors
      are well vascularized, with a high density of partially immature blood vessels
      and low numbers of infiltrating macrophages. The M-3 melanoma is well
      vascularized correlating with significant DNA uptake, however, necrosis and
      intensive infiltration by macrophages lead to rapid degradation of DNA. In
      contrast, the KB, 518A2, A549, and SW480 tumors are poorly vascularized,
      correlating with undetectable DNA uptake and gene expression. Using two different
      vector systems the data indicate that gene delivery to tumors in vivo is affected
      by tissue-dependent factors. Uptake of DNA into the tumor depends on
      vascularization of the tumor, while necrosis and macrophage infiltration may
      facilitate degradation of the DNA.

PMID- 12808439
TI  - Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer:
      a comparison of adenoviral vectors and liposomes.
AB  - Large bone defects resulting from nonunion fractures or tumour resections are
      common clinical problems. Recent studies have shown bone morphogenetic protein-2
      (BMP-2) gene transfer using adenoviral vectors to be a promising new therapeutic
      approach. However, comparative studies of different vectors are required to
      identify the optimal system for possible clinical trials. This study compares the
      use of liposome-mediated and adenoviral gene transfer for the generation of
      autologous BMP-2-producing bone marrow stromal cells (BMSC). Primary BMSC
      isolated from the rat femur were treated ex vivo with either an adenovirus or a
      liposome carrying human BMP-2 cDNA. The genetically modified cells were evaluated
      in vitro and transplanted into critical size defects in the rat mandible in vivo.
      BMSC treated with a reporter gene vector or untreated BMSC served as controls.
      The newly formed tissue was analysed by in situ hybridization, radiography and
      immunohistochemistry. Both groups of genetically modified cells produced BMP-2
      for at least 2 weeks, and markers of new bone matrix such as osteopontin and
      osteocalcin were observed within 2 weeks following gene transfer. In the liposome
      group, the critical size defects were found completely healed at 6 weeks after
      the gene transfer, whereas the more efficient adenoviral gene transfer allowed
      for complete bone healing within 4 weeks. None of the three control groups showed
      bone healing, not even after 8 weeks. Thus, both liposome-mediated and adenoviral
      BMP-2 gene transfer to primary BMSC are suitable methods to achieve the healing
      of critical size bone defects in rats. As liposomes have proven sufficient for
      this purpose and offer several advantages over any other vector, such as ease of
      preparation, theoretically no limitation of the size of the DNA, and less
      immunological and safety problems, they may represent the best vector system for
      future clinical trials of bone regeneration by BMP-2 gene therapy.

PMID- 12808440
TI  - Sustainable correction of junctional epidermolysis bullosa via transposon
      mediated nonviral gene transfer.
AB  - Sustainable correction of severe human genetic disorders of self-renewing
      tissues, such as the blistering skin disease junctional epidermolysis bullosa
      (JEB), is facilitated by stable genomic integration of therapeutic genes into
      somatic tissue stem cells. While integrating viral vectors can achieve this, they
      suffer from logistical and biosafety concerns. To circumvent these limitations,
      we used the Sleeping Beauty transposable element to integrate the LAMB3 cDNA into
      genomes of epidermal holoclones from six unrelated JEB patients. These cells
      regenerate human JEB skin that is normalized at the level of laminin 5 protein
      expression, hemidesmosome formation and blistering. Transposon-mediated gene
      delivery therefore affords an opportunity for stable gene delivery in JEB and
      other human diseases.

PMID- 12808441
TI  - Cytosolic delivery of antisense oligonucleotides by listeriolysin O-containing
      liposomes.
AB  - Antisense oligodeoxynucleotides (ODNs) possess great potential as sequence
      specific therapeutic agents. Sufficient concentrations of intact ODN must bypass
      membrane barriers and access the cytosol and nucleus, for ODNs to be
      therapeutically effective. A cytosolic delivery strategy was designed to improve
      the efficiency of ODN delivery in bone-marrow-derived macrophages. This liposome
      based formulation utilizes listeriolysin O (LLO), the endosomolytic hemolysin
      from Listeria monocytogenes, to mediate the escape of ODN from endocytic
      compartments into the cytosol. To monitor the cytosolic delivery of ODN,
      subcellular trafficking of fluorescently labeled ODNs was visualized using
      epifluorescence microscopy. The expression of target protein and mRNA after
      delivery was measured using flow cytometry and Northern blot analysis,
      respectively. ODN specific for murine intercellular adhesion molecule-1 (ICAM-1)
      encapsulated in LLO-liposomes was released to the cytosol and trafficked to the
      nucleus, efficiently and specifically suppressing activation-induced expression
      of ICAM-1 at both protein and mRNA levels. Delivery without LLO resulted in
      sequestration of ODN in vesicular compartments leading to little inhibition of
      ICAM-1 expression, which supports the requirement of LLO for efficient cytosolic
      delivery using this system. The data clearly demonstrate that LLO-mediated escape
      of ODN from intracellular vesicles is an effective approach to achieve full
      therapeutic antisense activity in cultured macrophages.

PMID- 12808442
TI  - Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors
      engineered to express IL-13 receptor alpha2 chain in vivo.
AB  - Interleukin-13 receptor (IL-13R) alpha2 chain plays a key role in ligand binding
      and internalization. We have recently demonstrated that this cytokine receptor
      chain has unique characteristics in tumor biology: it inhibits tumorigenicity of
      breast and pancreatic cancer in animal models. In this study, we have exploited
      IL-13Ralpha2 chain and established a novel approach for pancreatic cancer
      therapy. For this, a plasmid encoding the IL-13Ralpha2 chain gene was mixed with
      liposomes and injected into subcutaneously or orthotopically xenografted human
      pancreatic tumors in immunodeficient mice, followed by systemic or local therapy
      by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Ralpha2
      chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin.
      There was a dominant infiltration of cells including macrophages and natural
      killer cells in the regressing tumors. Since macrophages were found to produce
      nitric oxide, IL-13Ralpha2-targeted cancer therapy involved not only a direct
      tumor cell killing by IL-13 cytotoxin but also activation of innate immune
      response at the tumor site. Therefore, this approach may be a new powerful tool
      for pancreatic cancer or other localized cancer therapy.

PMID- 12808443
TI  - In vivo characterization of a prostate-specific antigen promoter-based suicide
      gene therapy for the treatment of benign prostatic hyperplasia.
AB  - To develop a novel gene therapeutic modality for the effective treatment of
      benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene
      therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex
      virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular
      ablation of epithelial cells with minimal systemic toxicity in canine prostate.
      Replication-defective recombinant adenoviral vectors containing HSV-TK gene under
      transcriptional control of long PSA promoter (Ad-PSA-HSV-TK) were developed and
      delivered in an situ manner. Briefly, laparotomies were performed and Ad-PSA-HSV
      TK (1 x 10(9) PFUs) was injected into the left lateral lobe of prostate only on
      days 1 and 7 with appropriate prodrug acyclovir in adult Beagle dogs. The
      therapeutic efficacy was evaluated on the 56th experimental day. The striking
      apoptosis of epithelial cells was identified in the treated left half of canine
      prostate on TUNEL assay. On immunohistochemical studies, there was markedly
      decreased number of PSA-secreting epithelial cells compared to control. Also
      significant atrophy of prostate glands, associated with dense infiltration of
      lymphocytes and plasma cells, was identified in the treated side. The PSA
      promoter-based suicide gene therapy induced highly selective and definite
      ablation of epithelial cells in benign canine prostate. Our novel approach could
      open opportunity of gene therapeutic modality for the treatment of clinical BPH.

PMID- 12808444
TI  - A molecular switch between alternative conformational states in the complex of
      Ran and importin beta1.
AB  - Several million macromolecules are exchanged each minute between the nucleus and
      cytoplasm by receptor-mediated transport. Most of this traffic is controlled by
      the small GTPase Ran, which regulates assembly and disassembly of the receptor
      cargo complexes in the appropriate cellular compartment. Here we applied dynamic
      force spectroscopy to study the interaction of Ran with the nuclear import
      receptor importin beta1 (impbeta) at the single-molecule level. We found that the
      complex alternates between two distinct conformational states of different
      adhesion strength. The application of an external mechanical force shifts
      equilibrium toward one of these states by decreasing the height of the interstate
      activation energy barrier. The other state can be stabilized by a functional Ran
      mutant that increases this barrier. These results support a model whereby
      functional control of Ran-impbeta is achieved by a population shift between pre
      existing alternative conformations.

PMID- 12808445
TI  - Structure of human dCK suggests strategies to improve anticancer and antiviral
      therapy.
AB  - Human deoxycytidine kinase (dCK) phosphorylates the natural deoxyribonucleosides
      deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA) and is an
      essential enzyme for the phosphorylation of numerous nucleoside analog prodrugs
      routinely used in cancer and antiviral chemotherapy. For many of these compounds,
      the phosphorylation step catalyzed by dCK is the rate-limiting step in their
      overall activation pathway. To determine the factors that limit the
      phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK
      to a resolution of 1.6 A in complex with its physiological substrate
      deoxycytidine and with the prodrugs AraC and gemcitabine. The structures reveal
      the determinants of dCK substrate specificity. Especially relevant to new prodrug
      development is the interaction between Arg128 and the hydrogen-bond acceptor at
      the sugar 2'-arabinosyl position of AraC and gemcitabine. On the basis of the
      structures, we designed a catalytically superior dCK variant that could be used
      in suicide gene-therapy applications.

PMID- 12808446
TI  - How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration.
AB  - The interaction of the plasma protein vitronectin with plasminogen activator
      inhibitor-1 (PAI-1) is central to human health. Vitronectin binding extends the
      lifetime of active PAI-1, which controls hemostasis by inhibiting fibrinolysis
      and has also been implicated in angiogenesis. The PAI-1-vitronectin binding
      interaction also affects cell adhesion and motility. For these reasons, elevated
      PAI-1 activities are associated both with coronary thrombosis and with a poor
      prognosis in many cancers. Here we show the crystal structure at a resolution of
      2.3 A of the complex of the somatomedin B domain of vitronectin with PAI-1. The
      structure of the complex explains how vitronectin binds to and stabilizes the
      active conformation of PAI-1. It also explains the tissue effects of PAI-1, as
      PAI-1 competes for and sterically blocks the interaction of vitronectin with cell
      surface receptors and integrins. Structural understanding of the essential
      biological roles of the interaction between PAI-1 and vitronectin opens the
      prospect of specifically designed blocking agents for the prevention of
      thrombosis and treatment of cancer.

PMID- 12808447
TI  - Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic
      fever.
AB  - Dengue virus presents a growing threat to public health in the developing world.
      Four major serotypes of dengue virus have been characterized, and epidemiological
      evidence shows that dengue hemorrhagic fever (DHF), the more serious
      manifestation of the disease, occurs more frequently upon reinfection with a
      second serotype. We have studied dengue virus-specific T-cell responses in Thai
      children. During acute infection, few dengue-responsive CD8+ T cells were
      recovered; most of those present showed an activated phenotype and were
      undergoing programmed cell death. Many dengue-specific T cells were of low
      affinity for the infecting virus and showed higher affinity for other, probably
      previously encountered strains. Profound T-cell activation and death may
      contribute to the systemic disturbances leading to DHF, and original antigenic
      sin in the T-cell responses may suppress or delay viral elimination, leading to
      higher viral loads and increased immunopathology.

PMID- 12808448
TI  - BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and
      reverses chronic renal injury.
AB  - Bone morphogenic protein (BMP)-7 is a 35-kDa homodimeric protein and a member of
      the transforming growth factor (TGF)-beta superfamily. BMP-7 expression is
      highest in the kidney, and its genetic deletion in mice leads to severe
      impairment of eye, skeletal and kidney development. Here we report that BMP-7
      reverses TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) by
      reinduction of E-cadherin, a key epithelial cell adhesion molecule. Additionally,
      we provide molecular evidence for Smad-dependent reversal of TGF-beta1-induced
      EMT by BMP-7 in renal tubular epithelial cells and mammary ductal epithelial
      cells. In the kidney, EMT-induced accumulation of myofibroblasts and subsequent
      tubular atrophy are considered key determinants of renal fibrosis during chronic
      renal injury. We therefore tested the potential of BMP-7 to reverse TGF-beta1
      induced de novo EMT in a mouse model of chronic renal injury. Our results show
      that systemic administration of recombinant human BMP-7 leads to repair of
      severely damaged renal tubular epithelial cells, in association with reversal of
      chronic renal injury. Collectively, these results provide evidence of cross talk
      between BMP-7 and TGF-beta1 in the regulation of EMT in health and disease.

PMID- 12808449
TI  - SSeCKS regulates angiogenesis and tight junction formation in blood-brain
      barrier.
AB  - The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and
      low permeability. BBB maintenance is important in the central nervous system
      (CNS) because disruption of the BBB may contribute to many brain disorders,
      including Alzheimer disease and ischemic stroke. The molecular mechanisms of BBB
      development remain ill-defined, however. Here we report that src-suppressed C
      kinase substrate (SSeCKS) decreases the expression of vascular endothelial growth
      factor (VEGF) through AP-1 reduction and stimulates expression of angiopoietin-1
      (Ang-1), an antipermeability factor in astrocytes. Conditioned media from SSeCKS
      overexpressing astrocytes (SSeCKS-CM) blocked angiogenesis in vivo and in vitro.
      Moreover, SSeCKS-CM increased tight junction proteins in endothelial cells,
      consequently decreasing [3H]sucrose permeability. Furthermore, immunoreactivity
      to SSeCKS gradually increased during the BBB maturation period, and SSeCKS
      expressing astrocytes closely interacted with zonula occludens (ZO)-1-expressing
      blood vessels in vivo. Collectively, our results suggest that SSeCKS regulates
      BBB differentiation by modulating both brain angiogenesis and tight junction
      formation.

PMID- 12808450
TI  - RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and
      accumulation in brain.
AB  - Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta
      levels in the brain and cerebral blood flow, providing a means of amplifying the
      Abeta-induced cellular stress underlying neuronal dysfunction and dementia.
      Systemic Abeta infusion and studies in genetically manipulated mice show that
      Abeta interaction with receptor for advanced glycation end products (RAGE)
      bearing cells in the vessel wall results in transport of Abeta across the blood
      brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1
      (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE
      ligand interaction suppresses accumulation of Abeta in brain parenchyma in a
      mouse transgenic model. These findings suggest that vascular RAGE is a target for
      inhibiting pathogenic consequences of Abeta-vascular interactions, including
      development of cerebral amyloidosis.

PMID- 12808452
TI  - Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory
      cells.
AB  - Immunological memory depends on the long-term maintenance of memory T cells.
      Although the factors that maintain CD8 T cell memory are well understood, those
      responsible for CD4 memory are not well defined. We have shown here that
      interleukin 7 (IL-7) was an important survival factor for CD4 memory T cells that
      together with T cell receptor (TCR) signals regulated homeostasis of the CD4
      memory population in lymphopenic conditions and in the intact immune system.
      Thus, IL-7 contributes to the maintenance of all naive and memory T cell subsets,
      and therefore controls the overall size of the T cell pool.

PMID- 12808451
TI  - Deletion of cytosolic phospholipase A2 promotes striated muscle growth.
AB  - Generation of arachidonic acid by the ubiquitously expressed cytosolic
      phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular
      homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2
      is a negative regulator of growth, specifically of striated muscle. We find that
      normal growth of skeletal muscle, as well as normal and pathologic stress-induced
      hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack
      the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that
      cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling.
      Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway,
      which results from the failure of 3-phosphoinositide-dependent protein kinase
      (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-zeta, a negative
      regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-zeta,
      correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic
      PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple
      growth-regulatory pathways.

PMID- 12808453
TI  - Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium
      and liver morphogenesis.
AB  - Although advances have been made in understanding cell differentiation, only
      rudimentary knowledge exists concerning how differentiated cells form tissues and
      organs. We studied liver organogenesis because the cell and tissue architecture
      of this organ is well defined. Approximately 60% of the adult liver consists of
      hepatocytes that are arranged as single-cell anastomosing plates extending from
      the portal region of the liver lobule toward the central vein. The basal surface
      of the hepatocytes is separated from adjacent sinusoidal endothelial cells by the
      space of Disse, where the exchange of substances between serum and hepatocytes
      takes place. The hepatocyte's apical surface forms bile canaliculi that transport
      bile to the hepatic ducts. Proper liver architecture is crucial for hepatic
      function and is commonly disrupted in disease states, including cirrhosis and
      hepatitis. Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is
      essential for morphological and functional differentiation of hepatocytes,
      accumulation of hepatic glycogen stores and generation of a hepatic epithelium.
      We show that Hnf4alpha is a dominant regulator of the epithelial phenotype
      because its ectopic expression in fibroblasts induces a mesenchymal-to-epithelial
      transition. Most importantly, the morphogenetic parameters controlled by
      Hnf4alpha in hepatocytes are essential for normal liver architecture, including
      the organization of the sinusoidal endothelium.

PMID- 12808454
TI  - Blindness and auditory impairment caused by loss of the sodium bicarbonate
      cotransporter NBC3.
AB  - Normal sensory transduction requires the efficient disposal of acid (H+)
      generated by neuronal and sensory receptor activity. Multiple highly sensitive
      transport mechanisms have evolved in prokaryotic and eukaryotic organisms to
      maintain acidity within strict limits. It is currently assumed that the
      multiplicity of these processes provides a biological robustness. Here we report
      that the visual and auditory systems have a specific requirement for H+ disposal
      mediated by the sodium bicarbonate cotransporter NBC3 (refs. 7,8). Mice lacking
      NBC3 develop blindness and auditory impairment because of degeneration of sensory
      receptors in the eye and inner ear as in Usher syndrome. Our results indicate
      that in certain sensory organs, in which the requirement to transduce specific
      environmental signals with speed, sensitivity and reliability is paramount, the
      choice of the H+ disposal mechanism used is limited.

PMID- 12808455
TI  - Spatial proximity of translocation-prone gene loci in human lymphomas.
AB  - Cancer cells frequently have disease-specific chromosome rearrangements. It is
      poorly understood why translocations between chromosomes recur at specific
      breakpoints in the genome. Here we provide evidence that higher-order spatial
      genome organization is a contributing factor in the formation of recurrent
      translocations. We show that MYC, BCL and immunoglobulin loci, which are
      recurrently translocated in various B-cell lymphomas, are preferentially
      positioned in close spatial proximity relative to each other in normal B cells.
      Loci in spatial proximity are non-randomly positioned towards the nuclear
      interior in normal B cells. This locus proximity is the consequence of higher
      order genome structure rather than a property of individual genes. Our results
      suggest that the formation of specific translocations in human lymphomas, and
      perhaps other tissues, is determined in part by higher-order spatial organization
      of the genome.

PMID- 12808456
TI  - Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals
      during limb patterning.
AB  - During limb outgrowth, signaling by bone morphogenetic proteins (BMPs) must be
      moderated to maintain the signaling loop between the zone of polarizing activity
      (ZPA) and the apical ectodermal ridge (AER). Gremlin, an extracellular Bmp
      antagonist, has been proposed to fulfill this function and therefore be important
      in limb patterning. We tested this model directly by mutating the mouse gene
      encoding gremlin (Cktsf1b1, herein called gremlin). In the mutant limb, the
      feedback loop between the ZPA and the AER is interrupted, resulting in abnormal
      skeletal pattern. We also show that the gremlin mutation is allelic to the limb
      deformity mutation (ld). Although Bmps and their antagonists have multiple roles
      in limb development, these experiments show that gremlin is the principal BMP
      antagonist required for early limb outgrowth and patterning.

PMID- 12808457
TI  - PGC-1alpha-responsive genes involved in oxidative phosphorylation are
      coordinately downregulated in human diabetes.
AB  - DNA microarrays can be used to identify gene expression changes characteristic of
      human disease. This is challenging, however, when relevant differences are subtle
      at the level of individual genes. We introduce an analytical strategy, Gene Set
      Enrichment Analysis, designed to detect modest but coordinate changes in the
      expression of groups of functionally related genes. Using this approach, we
      identify a set of genes involved in oxidative phosphorylation whose expression is
      coordinately decreased in human diabetic muscle. Expression of these genes is
      high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and
      correlated with total-body aerobic capacity. Our results associate this gene set
      with clinically important variation in human metabolism and illustrate the value
      of pathway relationships in the analysis of genomic profiling experiments.

PMID- 12808458
TI  - Early 'visual' cortex activation correlates with superior verbal memory
      performance in the blind.
AB  - The visual cortex may be more modifiable than previously considered. Using
      functional magnetic resonance imaging (fMRI) in ten congenitally blind human
      participants, we found robust occipital activation during a verbal-memory task
      (in the absence of any sensory input), as well as during verb generation and
      Braille reading. We also found evidence for reorganization and specialization of
      the occipital cortex, along the anterior-posterior axis. Whereas anterior regions
      showed preference for Braille, posterior regions (including V1) showed preference
      for verbal-memory and verb generation (which both require memory of verbal
      material). No such occipital activation was found in sighted subjects. This
      difference between the groups was mirrored by superior performance of the blind
      in various verbal-memory tasks. Moreover, the magnitude of V1 activation during
      the verbal-memory condition was highly correlated with the blind individual's
      abilities in a variety of verbal-memory tests, suggesting that the additional
      occipital activation may have a functional role.

PMID- 12808459
TI  - Non-invasive mapping of connections between human thalamus and cortex using
      diffusion imaging.
AB  - Evidence concerning anatomical connectivities in the human brain is sparse and
      based largely on limited post-mortem observations. Diffusion tensor imaging has
      previously been used to define large white-matter tracts in the living human
      brain, but this technique has had limited success in tracing pathways into gray
      matter. Here we identified specific connections between human thalamus and cortex
      using a novel probabilistic tractography algorithm with diffusion imaging data.
      Classification of thalamic gray matter based on cortical connectivity patterns
      revealed distinct subregions whose locations correspond to nuclei described
      previously in histological studies. The connections that we found between
      thalamus and cortex were similar to those reported for non-human primates and
      were reproducible between individuals. Our results provide the first quantitative
      demonstration of reliable inference of anatomical connectivity between human gray
      matter structures using diffusion data and the first connectivity-based
      segmentation of gray matter.

PMID- 12808460
TI  - A T-type calcium channel required for normal function of a mammalian
      mechanoreceptor.
AB  - The dorsal root ganglia (DRG) contain a variety of mechanoreceptors, but no
      molecular markers uniquely identify specific mechanoreceptor subtypes. We have
      used DNA microarrays and subtracted cDNA libraries to isolate genes that are
      specifically expressed by one type of mouse mechanoreceptor. The T-type calcium
      channel Ca(v)3.2 was exclusively expressed in the DRG by D-hair receptors, a very
      sensitive mechanoreceptor. Pharmacological blockade of T-type calcium channels
      indicated that this channel may be essential for normal D-hair receptor
      excitability including mechanosensitivity. This is the first evidence that a
      calcium channel is required for normal function of a vertebrate mechanoreceptor.

PMID- 12808461
TI  - Phosphoinositide profiling in complex lipid mixtures using electrospray
      ionization mass spectrometry.
AB  - Phosphoinositides (phosphorylated derivatives of phosphatidylinositol, PI) are
      versatile intracellular signaling lipids whose occurrence in low concentrations
      complicates direct mass measurements. Here we present a sensitive method to
      detect, identify and quantify phosphatidylinositol phosphate (PIP) and
      phosphatidylinositol bisphosphate (PIP(2)) with different fatty acid compositions
      (phosphoinositide profiles) in total lipid extracts by electrospray ionization
      mass spectrometry (ESI-MS). Using this method, we detected elevated
      concentrations of PIP2 in human fibroblasts from patients with Lowe syndrome, a
      genetic disorder that affects phosphoinositide metabolism. Saccharomyces
      cerevisiae cells deficient in enzymes involved in PIP metabolism--Sac1p, a
      phosphoinositide phosphatase, and Vps34p and Pik1p, a PI 3-kinase and PI 4
      kinase, respectively--showed not only different PIP concentrations but also
      differential changes in PIP profiles indicating metabolic and/or subcellular
      pooling. Mass spectrometric analysis of phosphoinositides offers unique
      advantages over existing approaches and may represent a powerful diagnostic tool
      for human diseases that involve defective phosphoinositide metabolism.

PMID- 12808462
TI  - Measurement of the millisecond activation switch of G protein-coupled receptors
      in living cells.
AB  - Hormones and neurotransmitters transduce signals through G protein-coupled
      receptors (GPCR). Despite their common signaling pathways, however, the responses
      they elicit have different temporal patterns. To reveal the molecular basis for
      these differences we have developed a generally applicable fluorescence-based
      technique for real-time monitoring of the activation switch of GPCRs in living
      cells. We used such direct measurements to investigate the activation of the
      alpha(2A)-adrenergic receptor (alpha(2A)AR; neurotransmitter) and the parathyroid
      hormone receptor (PTHR; hormone) and observed much faster kinetics than expected:
      approximately 40 ms for the alpha(2A)AR and approximately 1 s for the PTHR. The
      different switch times are in agreement with the different receptors' biological
      functions. Agonists and antagonists could rapidly switch the receptors on or off,
      whereas a partial agonist caused only a partial signal. This approach allows the
      comparison of agonist and partial agonist intrinsic activities at the receptor
      level and provides evidence for millisecond activation times of GPCRs.

PMID- 12808463
TI  - Noninvasive laser-induced photoacoustic tomography for structural and functional
      in vivo imaging of the brain.
AB  - Imaging techniques based on optical contrast analysis can be used to visualize
      dynamic and functional properties of the nervous system via optical signals
      resulting from changes in blood volume, oxygen consumption and cellular swelling
      associated with brain physiology and pathology. Here we report in vivo
      noninvasive transdermal and transcranial imaging of the structure and function of
      rat brains by means of laser-induced photoacoustic tomography (PAT). The
      advantage of PAT over pure optical imaging is that it retains intrinsic optical
      contrast characteristics while taking advantage of the diffraction-limited high
      spatial resolution of ultrasound. We accurately mapped rat brain structures, with
      and without lesions, and functional cerebral hemodynamic changes in cortical
      blood vessels around the whisker-barrel cortex in response to whisker
      stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic
      changes. This neuroimaging modality holds promise for applications in
      neurophysiology, neuropathology and neurotherapy.

PMID- 12808464
TI  - Biological containment of genetically modified Lactococcus lactis for intestinal
      delivery of human interleukin 10.
AB  - Genetically modified Lactococcus lactis secreting interleukin 10 provides a
      therapeutic approach for inflammatory bowel disease. However, the release of such
      genetically modified organisms through clinical use raises safety concerns. In an
      effort to address this problem, we replaced the thymidylate synthase gene thyA of
      L. lactis with a synthetic human IL10 gene. This thyA- hIL10+ L. lactis strain
      produced human IL-10 (hIL-10), and when deprived of thymidine or thymine, its
      viability dropped by several orders of magnitude, essentially preventing its
      accumulation in the environment. The biological containment system and the
      bacterium's capacity to secrete hIL-10 were validated in vivo in pigs. Our
      approach is a promising one for transgene containment because, in the unlikely
      event that the engineered L. lactis strain acquired an intact thyA gene from a
      donor such as L. lactis subsp. cremoris, the transgene would be eliminated from
      the genome.

PMID- 12808465
TI  - The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1
      DNA.
AB  - High mutation frequency during reverse transcription has a principal role in the
      genetic variation of primate lentiviral populations. It is the main driving force
      for the generation of drug resistance and the escape from immune surveillance. G
      to A hypermutation is one of the characteristics of primate lentiviruses, as well
      as other retroviruses, during replication in vivo and in cell culture. The
      molecular mechanisms of this process, however, remain to be clarified. Here, we
      demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme,
      catalytic polypeptide-like 3G; APOBEC3G), an endogenous inhibitor of human
      immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is
      able to induce G to A hypermutation in newly synthesized viral DNA. This effect
      can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that
      this viral DNA mutator is a viral defence mechanism in host cells that may induce
      either lethal hypermutation or instability of the incoming nascent viral reverse
      transcripts, which could account for the Vif-defective phenotype. Importantly,
      the accumulation of CEM15-mediated non-lethal hypermutation in the replicating
      viral genome could potently contribute to the genetic variation of primate
      lentiviral populations.

PMID- 12808466
TI  - Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent
      reverse transcripts.
AB  - Viral replication usually requires that innate intracellular lines of defence be
      overcome, a task usually accomplished by specialized viral gene products. The
      virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is
      required during the late stages of viral production to counter the antiviral
      activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide
      like 3G; also known as CEM15), a protein expressed notably in human T
      lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is
      non-infectious. APOBEC3G is closely related to APOBEC1, the central component of
      an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA.
      APOBEC family members also have potent DNA mutator activity through dC
      deamination; however, whether the editing potential of APOBEC3G has any relevance
      to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G
      exerts its antiviral effect during reverse transcription to trigger G-to-A
      hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act
      on a broad range of retroviruses in addition to HIV, suggesting that
      hypermutation by editing is a general innate defence mechanism against this
      important group of pathogens.

PMID- 12808467
TI  - Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal
      differentiation of NT2 cells.
AB  - MicroRNAs (miRNAs) are phylogenetically widespread small RNAs of 18-25
      nucleotides in length, and are found in animals and plants. These small RNAs can
      regulate gene expression at a translational level through interactions with their
      target messenger RNAs, and they have a role in the development of Caenorhabditis
      elegans and plants. Although more than two hundred miRNAs have been found in
      mammals, their mRNA targets remain to be identified. Here, we demonstrate that
      the expression of Hes1, basic helix-loop-helix transcriptional repressor, is
      regulated by miRNA-23 (miR-23) in NT2 cells. miR-23 is almost complementary to
      part of the coding region, just upstream of the termination codon, of Hes1 mRNA.
      Reduction in the level of miR-23 by small interfering RNAs resulted in the
      accumulation of Hes1, and hindered the retinoic-acid-induced neuronal
      differentiation of NT2 cells. Thus, our results indicate that miR-23 regulates
      the expression of Hes1 at the post-transcriptional level, and participates in
      retinoic-acid-induced neuronal differentiation of NT2 cells.

PMID- 12808469
TI  - cDNA cloning and high-level expression of a thrombin-like enzyme from Agkistrodon
      acutus venom.
AB  - Agkistrodon acutus (Guenther), a poisonous snake species of the family of
      Crotalidae, is mainly found south of the Yellow River in China. The main symptom
      of this poison is massive hemorrhage, in which thrombin-like enzymes (TLEs) in
      the venom play an important role. TLEs are abundant, especially in the venom of
      A. acutus. We isolated the total RNA from the venom gland tissue of A. acutus and
      amplified the cDNAs of the TLEs using reverse transcription-polymerase chain
      reaction (RT-PCR). The cDNAs were cloned into vector pThioHis B and were
      expressed as fusion proteins in the form of inclusion bodies, which accounted for
      nearly 50% of the total cell proteins. The inclusion bodies were washed,
      dissolved, refolded and purified by affinity chromatography. The purity was
      higher than 97%, as indicated by capillary zone electrophoresis. The renatured
      recombinant enzyme exhibited arginine esterase activity, as tested by the BAEE
      method, and also showed a fibrinogen cleavage effect, as detected by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). This method
      provides a fast and convenient system for studying the structure-function
      relationships in TLE isoenzymes, and also a practical way for mass production of
      TLEs in the pharmaceutical industry.

PMID- 12808468
TI  - Melanopsin and rod-cone photoreceptive systems account for all major accessory
      visual functions in mice.
AB  - In the mammalian retina, besides the conventional rod-cone system, a melanopsin
      associated photoreceptive system exists that conveys photic information for
      accessory visual functions such as pupillary light reflex and circadian photo
      entrainment. On ablation of the melanopsin gene, retinal ganglion cells that
      normally express melanopsin are no longer intrinsically photosensitive.
      Furthermore, pupil reflex, light-induced phase delays of the circadian clock and
      period lengthening of the circadian rhythm in constant light are all partially
      impaired. Here, we investigated whether additional photoreceptive systems
      participate in these responses. Using mice lacking rods and cones, we measured
      the action spectrum for phase-shifting the circadian rhythm of locomotor
      behaviour. This spectrum matches that for the pupillary light reflex in mice of
      the same genotype, and that for the intrinsic photosensitivity of the melanopsin
      expressing retinal ganglion cells. We have also generated mice lacking melanopsin
      coupled with disabled rod and cone phototransduction mechanisms. These animals
      have an intact retina but fail to show any significant pupil reflex, to entrain
      to light/dark cycles, and to show any masking response to light. Thus, the rod
      cone and melanopsin systems together seem to provide all of the photic input for
      these accessory visual functions.

PMID- 12808470
TI  - Effect of vitamin E and vitamin C combination on experimental influenza virus
      infection.
AB  - Successful antioxidant treatment of the so-called "free radical diseases" has
      been reported in the literature. In this study we examined the preventive effect
      of vitamin E and vitamin C, alone and in combination, on the damage caused by
      influenza virus infection (IVI). Male mice (ICR), infected with influenza virus
      A/2/68/(H3N2) (1.5 of LD(50)), were administered single once-daily doses of
      vitamin E (60 mg/kg b.w.) and vitamin C (80 mg/kg b.w.) intraperitoneally (3 days
      before virus inoculation). On the 5th and 7th day, respectively, after virus
      inoculation, animals were decapitated. Monooxygenase enzyme activity
      (ethylmorphine N-demethylase, amidopyrin N-demethylase, analgin N-demethylase,
      aniline hydroxylase, cytochrome P-450 content and NADPH-cytochrome C reductase
      [CCR]) was determined in liver 9000 x g supernatant. Primary and secondary
      products of lipid peroxidation (LPO; conjugated dienes [CD] and TBA-reactive
      substances) were measured in blood plasma, lung and liver 9000 x g supernatant.
      Vitamin E effectively restored LPO-levels increased by IVI. The effect of vitamin
      C was similar, but slighter. The combination (vitamin E + C) had greater effect
      on LPO levels than their separate administration. P-450-dependent monooxygenase
      activity was significantly restored and more pronounced cytochrome P-450 content
      and NADPH-CCR activity was noted. The preventive effect of vitamin E was stronger
      than the effect of vitamin C, but the combination (vitamin E + C) had the
      strongest effect. The superior protective effect of the combination is probably
      due to vitamin C's repairing effect on vitamin E's tocopheroxyl radical.

PMID- 12808471
TI  - Experimental anxiety and antiepileptics: the effects of valproate and vigabatrin
      in the mirrored chamber test.
AB  - The potential anxiolytic-like effects of valproate (VPA; 200, 300 and 400 mg/kg
      i.p.) and vigabatrin (GVG; 150, 300 and 450 mg/kg i.p.) were evaluated in an
      experimental model of anxiety in mice. The mirrored chamber test was the model
      selected. In this study, anxiogenic-like behavior was induced by pretreatment
      with m-chlorophenylpiperazine hydrochloride (m-CPP; 1 mg/kg i.p.). For
      comparative purposes, the effects of an established reference anxiolytic,
      lorazepam (LOR; 0.025, 0.05 and 0.10 mg/kg i.p.) were also evaluated. Results
      showed that 2 weeks of repeated treatment with 200, 300 and 400 mg/kg of VPA or,
      to a lesser extent, 300 and 450 mg/kg i.p. of GVG, antagonized the anxiogenic
      effects of m-CPP. VPA induced behavioral changes very similar to those produced
      by lorazepam, i.e., a decrease in the latency time to enter the mirrored chamber
      and an increase in the time spent in the mirrored chamber. The anxiolytic-like
      potency of GVG was lower than that of VPA in this test. In conclusion, these data
      provide additional evidence for the anxiolytic-like effects of VPA and
      substantiate its role in the treatment of anxiety disorders and in the withdrawal
      state of ethanol or sedative-hypnotics.

PMID- 12808472
TI  - Fluoxetine suppresses morphine tolerance and dependence: modulation of NO
      cGMP/DA/serotoninergic pathways.
AB  - Although the phenomenon of opioid tolerance and dependence has been widely
      investigated, neither opioid nor non-opioid mechanisms are completely understood.
      In view of the modulation of 5-HT transport into presynaptic terminals in the
      brain by nitric oxide (NO) via cGMP, and the existence of a tonic 5-HTergic
      inhibition of dopamine release, the present study investigated the effect of
      fluoxetine, a selective serotonin reuptake inhibitor, and NO modulators L-N(G)
      nitroarginine methyl ester (L-NAME; NO synthase inhibitor) and L-Arginine
      (substrate for nitric oxide synthase) alone or in combination against morphine
      tolerance and dependence. Animals developed tolerance to the antinociceptive
      effect of morphine (10 mg/kg s.c. twice daily) on day 3 and the degree of
      tolerance was further enhanced on days 9 and 10. The development of tolerance to
      the antinociceptive effect of morphine was delayed by prior administration of
      fluoxetine (10 mg/kg i.p, twice daily for 9 days) and L-NAME (10 mg/kg i.p. twice
      daily for 9 days) alone or in combination. It was accentuated by L-Arginine (50
      mg/kg i.p. twice daily for 9 days) alone or in combination with fluoxetine (10
      mg/kg i.p. twice daily for 9 days). Similarly, fluoxetine (10 mg/kg i.p.) or L
      NAME (10 mg/kg i.p.), when administered acutely on day 10, reversed morphine
      induced tolerance. L-Arginine (50 mg/kg i.p.) however, when administered acutely
      on day 10, accentuated morphine tolerance. Fluoxetine (10 mg/kg i.p. twice daily
      for 9 days) suppressed the development of morphine dependence as assessed by
      naloxone (2 mg/kg i.p.)-precipitated withdrawal jumps. This suppression of
      dependence was potentiated by L-NAME (10 mg/kg i.p. twice daily for 9 days) and
      reversed by L-Arginine (50 mg/kg i.p. twice daily for 9 days), respectively.
      Acute administration of the respective drugs on day 10 modulated morphine
      dependence in a similar fashion. L-Arginine also reversed fluoxetine-induced
      weight loss in morphine-dependent animals. The present study demonstrated that
      fluoxetine suppressed the dependence and development of tolerance to the
      antinociceptive effect of morphine. Fluoxetine-induced suppression was
      potentiated by L-NAME and accentuated by L-Arginine. The results therefore
      suggest that a complex phenomenon such as morphine tolerance and dependence might
      involve close interplay of the NO-c GMP/5-HT/DA receptor system. To the best of
      the authors' knowledge, this is the first report to suggest targeting this
      cascade for amelioration of opioid tolerance and withdrawal syndrome.

PMID- 12808473
TI  - Effect of paeonol on L-type calcium channel in rat ventricular myocytes.
AB  - In order to study the possible mechanisms of paeonol on the cardiovascular
      system, the effect of paeonol on L-type Ca(2+) channel current (I(Ca,L)) was
      studied in rat ventricular myocytes using the whole cell patch-clamp technique.
      Exposure to paeonol (approximately 10 to 1000 microm/l) resulted in a
      concentration-dependent inhibition of peak I(Ca,L), with a half maximum
      inhibition concentration, IC(50), of 561 microm/l. Paeonol 600 microm/l inhibited
      I(Ca,L) by 55.3%, shifted the steady state activation and inactivation curve of
      I(Ca,L) to more positive and negative potentials, respectively, tended to prolong
      the recovery of I(Ca,L) from inactivation and did not have a use-dependent
      effect. However, the current-voltage relationship and reversal potential of
      I(Ca,L) were not altered. These results suggest that the protection by paeonol
      against myocardial injury is due to its blocking effect on I(Ca,L).

PMID- 12808474
TI  - Involvement of L-arginine-nitric oxide system in the response of isolated trachea
      to reactive oxygen species.
AB  - The aim of this study was to investigate the effect of reactive oxygen species
      (ROS), generated by electrolysis of Krebs-Henseleit solution (GE-KHS), on
      isolated guinea pig trachea and to assess the possible involvement of nitric
      oxide (NO) in the observed effects. The isolated trachea was superfused in GE
      KHS, generating H2O2 and hypochlorous acid (HOCl), both of which slowly increased
      in the organ bath and reached final stable concentrations of 42 and 63 microM,
      respectively, at the rate of 20 ml/min(-1), and 261 and 245 microM, respectively,
      at the rate of 5 ml/min(-1). ROS GE-KHS-induced relaxation of tracheal rings was
      preceded by a small transient contraction in 40% and 65% of experiments when
      tracheal rings were superfused at the rate of 20 ml/min(-1) and 5 ml/min(-1),
      respectively. Removal of tracheal epithelium abolished the relaxation of the
      trachea induced by ROS GE-KHS and unmasked or potentiated trachealis contraction.
      The ROS GE-KHS-induced changes in trachealis tension were accompanied by an
      increase in thiobarbituric acid reactive substances (TBARS) and a decrease in
      nonprotein (NP) thiols in the trachea. These changes were inhibited by treatment
      with the antioxidant N-acetylcysteine (100 microM). Pretreatment of tracheal
      rings with the inhibitor of NO synthase (NOS) N(omega)-nitro-L-arginine (L-NOARG;
      100 microM) for 20 min prior to exposure to ROS GE-KHS decreased the ROS GE-KHS
      induced relaxation. When L-NOARG (100 microM) was present in the superfusing
      solution, not only 20 min before but also during superfusion with ROS GE-KHS, the
      evoked trachealis relaxation was reduced in the first 15 min but was enhanced in
      the 30th min. This late enhancement of relaxation was accompanied by a 12-fold
      increase in nitric oxide metabolites (NO(x)). ROS GE-KHS-induced elevation of
      TBARS levels in the trachea was decreased to 63% by pretreatment with L-NOARG
      (100 microM). Elevation of TBARS levels induced by incubation of brain liposomes
      with a hydroxyl radical generating system was decreased to 90% by L-NOARG (10,
      100 microM), while the antioxidant stobadine (100 microM) nearly completely
      inhibited the evoked lipid peroxidation. In comparison with Trolox, L-NOARG
      exerted a slight scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl radical.
      The presence of L-arginine and D-arginine in the superfusion fluid for 15-20 min
      before and during exposure of the trachea to ROS GE-KHS inhibited trachealis
      relaxation. Results indicate that epithelium derived NO may participate in the
      response of guinea pig trachea to ROS GE-KHS. The presence of L-NOARG in the
      bathing fluid during superfusion with ROS GE-KHS gave rise to NO(x), with
      relaxing activity. L- and D-arginine induced an inhibition of the relaxatory
      response to ROS GE-KHS and partially prevented a ROS-induced decrease in NP
      thiols. The involvement of the small antioxidant effects of L-NOARG and L- and D
      arginine in the above mentioned actions of L-NOARG and L-arginine requires
      additional investigation.

PMID- 12808475
TI  - Pharmacological studies on resveratrol.

PMID- 12808476
TI  - Recent developments in clinical trials for bronchial asthma.
AB  - Bronchial asthma is a chronic inflammatory disorder of the airways. Currently
      available antiinflammatory treatments, represented by inhaled corticosteroids
      (ICS), are highly effective in controlling symptoms in the majority of patients,
      but their potential side effects have led to the use of adjunctive or alternative
      therapies and to the development of new therapies. Most of these new agents are
      aimed at inhibiting various components of allergic inflammation, with better
      safety profiles than ICS. They include inhibitors of phosphodiesterase 4,
      cytokine modulators, chemokine receptor antagonists and antisense
      oligonucleotides.

PMID- 12808477
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies knowledge area of Prous Science Integrity,
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007,
      adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid
      hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra,
      aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1
      vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate,
      bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride,
      cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa
      (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997,
      epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib,
      everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1
      cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132,
      ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine
      hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine
      hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride,
      miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP,
      parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept,
      pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000,
      prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan,
      ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306,
      stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib,
      trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

PMID- 12808478
TI  - Anemia in chronic congestive heart failure: frequency, prognosis, and treatment.
AB  - Chronic heart failure (CHF) is a leading cause of morbidity and mortality.
      Although a precise definition for a cut-off value of hemoglobin level for anemia
      is still lacking, it has recently been found to be a common complication in CHF,
      occurring in 10-20% of patients. There are several possible pathogenetic
      mechanisms for anemia in CHF, and a precise underlying cause is found in only a
      minority of patients. In CHF, more than 50% of anemia cases are considered to be
      'anemia in chronic illness'. In CHF patients, low hemoglobin values directly
      relate to poor peak oxygen consumption, disabling symptoms, and impaired
      survival. Recent pilot studies showed that correction of anemia with
      erythropoietin and iron may lead to improvement in symptoms and exercise
      capacity. These issues need to be tested in larger, double-blind, randomized,
      placebo-controlled trials before anemia treatment becomes routine in patients
      with CHF.

PMID- 12808479
TI  - Mitral valve repair as an alternative treatment for heart failure patients.
AB  - Heart failure is one of the leading causes of hospitalization worldwide. Mitral
      regurgitation (MR) is a known complication of end-stage cardiomyopathy and is
      associated with a poor prognosis. Historically, these patients were managed
      medically and frequently with mitral valve replacement, both of which have
      unfavorable long-term outcomes. Over a 10-year period, we studied 167 patients
      with cardiomyopathy and severe MR who underwent mitral valve repair. These
      patients with 4+ MR, a mean left ventricular ejection fraction (LVEF) of 14+/-6
      and New York Heart Association (NYHA) class III or IV congestive heart failure
      (CHF) were prospectively studied. All patients underwent mitral valve repair with
      an undersized annuloplasty ring. There was one intra-operative death and eight 30
      day mortalities. Intra-operative echocardiography revealed no MR in most patients
      and trivial to mild MR in seven patients. There were 26 late deaths; two of these
      patients had progression of CHF and underwent transplantation. The 1-, 2-, and 5
      year actuarial survival rates were 82%, 71%, and 52%, respectively. NYHA class
      was improved for all patients from a pre-operative mean of 3.2+/-0.2 to 1.8+/-0.4
      postoperatively. At 24-month follow-up, all patients demonstrated improvement in
      LVEF, cardiac output, and end-diastolic volume, with a reduction in sphericity
      index and regurgitant volume. Mitral valve repair utilizing an undersized
      annuloplasty ring is safe and effectively corrects MR in cardiomyopathic
      patients. All of the observed changes contribute to reverse remodeling and
      restoration of the normal LV geometric relationship. Mitral valve repair offers a
      new strategy for patients with MR and end-stage cardiomyopathy.

PMID- 12808480
TI  - The emerging role of brain natriuretic peptide in the management of acute and
      chronic heart failure in outpatients.
AB  - B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac
      ventricles. It is released as N-terminal pro-BNP (NT-proBNP) and cleaved
      enzymatically to the NT fragment and the immunoreactive BNP. Measurement of BNP
      is now available as a rapid bedside assay that is easily available to physicians
      in an office, clinic, emergency department, or inpatient setting. It has proven
      utility in the emergency department diagnosis of congestive heart failure (CHF)
      in patients with unclear causes of dyspnea. The use of BNP level as a criterion
      for hospital admission has been studied as has its use as an aid in decision
      making regarding the adequacy of treatment and readiness for hospital discharge.
      Treatment of chronic CHF in outpatients using BNP as a guide for the intensity of
      pharmacological therapy shows promise in further decreasing the rate of adverse
      events associated with this diagnosis. Other uses for BNP measurement include the
      prognostication of CHF exacerbation and myocardial infarction, and screening
      those at risk to identify patients that may benefit from early intervention and
      treatment of early CHF.

PMID- 12808481
TI  - Classes of antianginal compounds: old and new--therapeutic implications.

PMID- 12808483
TI  - Heart failure complicated by atrial fibrillation: mechanistic, prognostic, and
      therapeutic implications.
AB  - Atrial fibrillation and congestive heart failure are two distinct clinical
      entities that are responsible for significant morbidity and mortality in the
      Western world. Hypertension, coronary artery disease, and nonischemic
      cardiomyopathy represent the most prevalent underlying pathologies of both
      diseases, implying a coincidence of both in many patients. The prevalence of
      atrial fibrillation with a progressive degree of congestive heart failure is
      increasing, as judged by New York Heart Association functional class. Moreover,
      the presence of congestive heart failure has been identified as one of the most
      powerful independent predictors of atrial fibrillation, with a sixfold increase
      in relative risk of its development. On the other hand, atrial fibrillation can
      cause or significantly aggravate symptoms of congestive heart failure in
      previously asymptomatic or well-compensated patients. In some patients,
      symptomatic dilated cardiomyopathy may develop over time entirely due to atrial
      fibrillation with rapid ventricular rates. Upon restoration of sinus rhythm, this
      type of "tachymyopathy" has been shown to be often reversible. Recent
      investigations of the physiologic and structural changes of the atrial myocardium
      ("electrical and structural remodeling") have shown that neurohumoral activation,
      fibrosis, and apoptosis are demonstrable with both diseases. On the other hand,
      experimental data suggest that the substrates of atrial fibrillation in
      congestive heart failure are different from those of pure atrial tachycardia
      related forms of atrial fibrillation. This review highlights the clinical and
      pathophysiologic similarities and differences of atrial fibrillation and
      congestive heart failure relevant to the understanding, treatment, and prevention
      of these diseases in the population at risk.

PMID- 12808482
TI  - Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in
      heaven?
AB  - A relatively novel group of drugs that inhibit the funny current in the sinus
      node pacemaker cells, the so-called specific bradycardic agents, are likely to
      play a significant role in the management of a wide range of cardiovascular
      disorders, including the sinus tachyarrhythmias. This comprehensive review
      initially provides an insight into these agents, their historical background, and
      their mechanism of action. It then discusses the differential diagnosis of the
      sinus tachyarrhythmias (normal sinus tachycardia, inappropriate sinus
      tachycardia, postural orthostatic tachycardia syndrome, and sinus node reentry
      tachycardia), elaborates on their pathophysiologic basis, and provides up-to-date
      evidence-based information on their optimum management. The specific bradycardic
      agents, by the very nature of their mode of action, may prove ideal therapies for
      the management of the sinus tachyarrhythmias, and this is explored at every
      stage.

PMID- 12808484
TI  - Vasopressor agents for cardiopulmonary resuscitation.
AB  - The primary goal of cardiopulmonary resuscitation is to reestablish blood flow to
      vital organs until spontaneous circulation is restored. Adrenergic vasopressor
      agents produce systemic vasoconstriction. This increases aortic diastolic
      pressure, and consequently, coronary and cerebral perfusion pressures. The
      pharmacologic responses to the adrenergic agents are mediated by a group of
      receptors that are classified as alpha (alpha), including alpha1 and alpha2, and
      beta (beta), including beta1 and beta2. Epinephrine, which has each of these
      adrenergic actions, has been the preferred adrenergic agent for the management of
      cardiac arrest for almost 40 years. Its primary efficacy is due to its alpha
      adrenergic vasopressor effects. This contrasts with its beta-adrenergic actions,
      which are inotropic, chronotropic, and vasodilator. Accordingly, beta-adrenergic
      actions prompt increases in myocardial oxygen consumption, ectopic ventricular
      arrhythmias, and transient hypoxemia due to pulmonary arteriovenous shunting.
      This may account for the failure to demonstrate that epinephrine improves
      ultimate outcomes in human victims of cardiac arrest. Major interest has more
      recently been focused on selective alpha-adrenergic agonists. Both alpha1
      agonists and alpha2-agonists are peripheral vasopressors. However, rapid
      desensitization of alpha1-adrenergic receptors occurs during cardiopulmonary
      resuscitation. Moreover, alpha1-adrenergic receptors are present in the
      myocardium, and beta1-agonists, like beta-adrenergic agonists, increase
      myocardial oxygen consumption. If they cross the blood-brain barrier, alpha2
      adrenoceptor agonists also have centrally acting vasodilator effects. In the
      absence of central nervous system access, alpha2-adrenergic agonists have
      selective peripheral vasoconstrictor effects. Under experimental conditions of
      cardiopulmonary resuscitation, selective alpha2-agonists, which do not gain
      entrance into the brain, produce only systemic vasoconstriction. Experimentally,
      these selective alpha2-agonists are as effective as epinephrine for initial
      cardiac resuscitation and have the additional advantage of minimizing myocardial
      oxygen consumption during the global myocardial ischemia of cardiac arrest.
      Accordingly, myocardial ischemic injury during cardiopulmonary resuscitation is
      minimized, and postresuscitation myocardial function is preserved with improved
      survival.

PMID- 12808485
TI  - Efficacy of alternate-day dosing versus daily dosing of atorvastatin.
AB  - BACKGROUND: Atorvastatin is a synthetic inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase. In placebo-controlled trials, it has been shown
      to achieve significant dose-dependent reductions in low-density lipoprotein
      cholesterol, total cholesterol, and triglycerides. This trial compared the
      efficacy of daily atorvastatin administration with that of alternate-day dosing.
      METHODS: This was a randomized, prospective, nonblinded, controlled clinical
      trial. Fifty-four patients with low-density lipoprotein cholesterol of 100 to 200
      mg/dL were enrolled. Baseline fasting lipid profile (total cholesterol, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol, and
      triglycerides), liver function tests (aspartate transaminase and alanine
      aminotransferase), and creatine kinase were drawn. Patients were randomized to
      three atorvastatin dose groups. Group I received 10 mg of atorvastatin every day,
      Group II received 10 mg every other day, and Group III received 20 mg every other
      day. After 6 weeks of treatment with atorvastatin, fasting lipid profiles, liver
      function tests, and creatine kinase concentrations were redrawn. Compliance to
      treatment was assessed at each visit. RESULTS: Of the 54 patients enrolled, 46
      completed the study. All three regimens significantly reduced total cholesterol
      and low-density lipoprotein cholesterol compared to baseline. No statistically
      significant differences existed between the three groups in regards to total, or
      a percentage, decrease in total cholesterol and low-density lipoprotein
      cholesterol at 6 weeks compared to baseline. All regimens were well tolerated and
      none of the patients had a significant elevation of liver enzymes or creatine
      kinase during the course of the study. CONCLUSION: Alternate-day dosing of
      atorvastatin is an efficacious and safe alternative to daily dosing.

PMID- 12808486
TI  - The combination of nebivolol plus pravastatin is associated with a more
      beneficial metabolic profile compared to that of atenolol plus pravastatin in
      hypertensive patients with dyslipidemia: a pilot study.
AB  - Nebivolol, a selective beta1-lipophilic blocker, achieves blood pressure control
      by modulating nitric oxide release in addition to b-blockade. This dual mechanism
      of action could result in minimum interference with lipid metabolism compared to
      atenolol, a classic beta1-selective blocker. Hypertensive patients commonly
      exhibit lipid abnormalities and frequently require statins in combination with
      the anti-hypertensive therapy. We conducted this trial in order to clarify the
      effect on the metabolic profile of beta-blocker therapy with atenolol or
      nebivolol alone, or in conjunction with pravastatin. Thirty hypertensive
      hyperlipidemic men and women (total cholesterol >240 mg/dL [6.2 mmol/L], low
      density lipoprotein cholesterol >190 mg/dL [4.9 mmol/L], triglycerides <500 mg/dL
      [5.6 mmol/L]) were separated in two groups. One group consisted of 15 subjects on
      atenolol therapy (50 mg daily), and the other group included 15 subjects on
      nebivolol therapy (5 mg daily). After 12 weeks of beta-blocker therapy,
      pravastatin (40 mg daily) was added in both groups for another 12 weeks. Atenolol
      significantly increased triglyceride levels by 19% (P=.05), while nebivolol
      showed a trend to increase high-density lipoprotein cholesterol by 8% (NS) and to
      decrease triglyceride levels by 5% (NS). Atenolol significantly increased
      lipoprotein(a) by 30% (P=.028). Fibrinogen levels were equally and not
      significantly decreased in both groups by 9% and 7%, respectively. Furthermore,
      atenolol and nebivolol decreased serum high-sensitivity C-reactive protein levels
      by 14% (P=.05) and 15% (P=.05), respectively. On the other hand, both atenolol
      and nebivolol showed a trend to increase homocysteine levels (NS) by 13% and 11%,
      respectively. Although uric acid levels remained the same, atenolol significantly
      increased the fractional excretion of uric acid by 33% (P=.03). Following
      nebivolol administration, glucose levels remained the same, while insulin levels
      were reduced by 10% and the HOMA index (fasting glucose levels multiplied by
      fasting insulin levels and divided by 22.5) was reduced by 20% (P=.05). There
      were no significant differences between the two patient groups in the measured
      parameters after the administration of beta-blockers, except for triglycerides
      (P<.05) and the HOMA index (P=.05). The addition of pravastatin to all patients
      (n=30) decreased total cholesterol by 21% (P<.001), low-density lipoprotein
      cholesterol by 28% (P<.001), apolipoprotein-B by 22% (P<.001), apolipoprotein-E
      by 15% (P=.014) and lipoprotein(a) levels by 12% (P=.023). Moreover, homocysteine
      levels and C-reactive protein were reduced by 17% (P=.05) and 43% (P=.05),
      respectively. We conclude that nebivolol seems to be a more appropriate therapy
      in hypertensive patients with hyperlipidemia and carbohydrate intolerance.
      Finally, the addition of pravastatin could further correct the well-established
      predictors of cardiovascular events.

PMID- 12808487
TI  - Resident cardiac mast cells and ischemia-reperfusion injury.
AB  - BACKGROUND: The intense inflammatory reaction following reperfusion of ischemic
      myocardium has been implicated as a factor in the extension of myocardial injury.
      One of the therapeutic goals of modern cardiology is to design strategies to
      limit the infarct size following myocardial infarction. A sound understanding of
      the inflammatory cascade that involves the release of various proinflammatory
      mediators from cardiac cells is necessary before a specific intervention is
      pursued. OBSERVATION: Summarized is the role of resident cardiac mast cells,
      which are noted to release inflammatory mediators, in ischemia-reperfusion
      induced myocardial injury. Various pharmacologic interventions, such as disodium
      cromoglycate and ketotifen, that stabilize cardiac mast cells, or agents such as
      chlorpheniramine and cetirizine that prevent their degranulation during ischemia
      and reperfusion, may prove to be potential therapeutic agents to limit or salvage
      ischemia-reperfusion-induced injury. CONCLUSION: On the basis of the effects of
      histamine H1 antagonists, adrenoceptor blockers, cellular calcium and nitric
      oxide modulators, as well as inhibitors of phosphodiesterase and mitogen
      activated protein kinase on mast cells, cardiac resident mast cells may represent
      a novel target for the development of cardioprotective agents.

PMID- 12808489
TI  - Low density lipoproteins modulate collagen metabolism in fibroblasts.
AB  - High levels of low-density lipoprotein are associated with atherosclerosis, and
      myocardial and arterial remodeling. We postulated that low-density lipoprotein
      influences collagen synthesis and degradation in fibroblasts as a potential
      mechanism of tissue remodeling. Incubation of cultured human skin fibroblasts
      with low-density lipoproteins resulted in a time-dependent and dose-dependent
      increase in the secretion of matrix metalloproteinase activity measured by
      gelatin zymography. Western blot analysis showed a concomitant increase in matrix
      metalloproteinase-1 protein. Northern blot analysis demonstrated an increase in
      collagen I messenger RNA after treatment with low-density lipoprotein. The matrix
      metalloproteinase-1 secretory response of fibroblasts to low-density lipoprotein
      was attenuated by heparin, which inhibits low-density lipoprotein uptake through
      the low-density lipoprotein-receptor. These observations suggest that low-density
      lipoprotein has a regulatory effect on collagen metabolism in fibroblasts.

PMID- 12808488
TI  - Cocaine produces cardiac hypertrophy by protein kinase C dependent mechanisms.
AB  - BACKGROUND: Chronic cocaine users can have as much as a 69% increase in left
      ventricular muscle mass without associated increases in arterial blood pressure,
      heart rate, renin, aldosterone, or cortisol. We determined whether cocaine
      directly increases cardiomyocyte protein content and whether protein kinase C is
      important in this process. METHODS AND RESULTS: Adult rat cardiomyocytes were
      isolated and grown in cultures. In Series I experiments, cocaine, 10(-8) to 10(
      6) M, or vehicle, in the absence or presence of phentolamine or metoprolol, was
      added to each culture and the cells were subsequently harvested. In Series II,
      cocaine, 10(-6) M, cocaine, 10(-6) M, plus bisindolylmaleimide, 10(-6) M, a
      protein kinase C inhibitor, or vehicle were added to each culture and the cells
      subsequently harvested. We determined the total protein content, the content of
      alpha-myosin and fetal beta-myosin heavy-chain protein, and the presence of
      protein kinase C isoforms in the cardiomyocyte soluble and particulate fractions.
      Protein kinase C translocation from the soluble to particulate fraction is
      indicative of activation. In Series III, we determined the cocaine effects on
      ERK, SAPK/JNK, and p38. In Series I, cocaine, 10(-8) to 10(-6) M, dose
      dependently increased myocyte protein content by as much as 28%+/-2% (P<.001) and
      fetal beta-myosin heavy-chain protein content by 80%+/-2% (P<.001). Neither
      phentolamine nor metoprolol inhibited this process. In Series II, we determined
      that ventricular myocytes contain alpha (alpha), beta (beta), delta (delta),
      epsilon (epsilon), and zeta (zeta) protein kinase C isoforms. Cocaine, 10(-6) M,
      caused a 45+/-5% increase (P<.001) in protein kinase Calpha in the particulate
      fraction. The addition of a protein kinase C inhibitor to the myocyte cultures
      prevented the cocaine-induced translocation of protein kinase Calpha and limited
      the increase in beta-myosin heavy-chain protein content by >75% (P<.001).
      However, cocaine did not increase the phosphorylation of ERK, SAPK/JNK or p38 in
      Series III. CONCLUSIONS: Cocaine increases adult cardiomyocyte protein content by
      protein kinase Calpha-dependent mechanisms, and this process can contribute to
      the cardiac hypertrophy and cardiomyopathy that results from chronic cocaine use.

PMID- 12808490
TI  - Omapatrilat induces profound renal vasodilation but does not affect coronary
      hemodynamics.
AB  - BACKGROUND: Omapatrilat has potent enzymatic inhibitory effects on the
      angiotensin-converting enzyme and neutral endopeptidase. The prolonged effects of
      this inhibition on systemic and regional hemodynamics, cardiovascular mass, and
      hydroxyproline concentration in spontaneously hypertensive rats were studied. The
      contribution of endogenous bradykinin on the cardiovascular actions of
      omapatrilat in this genetic model of hypertension was also investigated. METHODS
      AND RESULTS: Systemic and regional hemodynamics (radionuclide-labeled
      microspheres), left and right ventricular and aortic masses, and hydroxyproline
      concentration were determined in 35-week-old spontaneously hypertensive rats
      after 12 weeks of treatment with omapatrilat (40 mg/kg/day), with and without the
      bradykinin receptor antagonist icatibant (500 microg/kg/day). Omapatrilat
      decreased mean arterial pressure, reducing total peripheral resistance as well as
      decreased left ventricular and aortic mass indices. It also induced a profound
      renovasodilation associated with a decrease renal vascular resistance that
      markedly increased renal blood flow. Coronary hemodynamics and left ventricular
      hydroxyproline concentration remained unaltered. Concomitant blockade of
      bradykinin receptors partially attenuated the hypotensive effect of omapatrilat
      and its effect on aortic mass; and icatibant did not influence the
      renovasodilation. CONCLUSION: Omapatrilat produced profoundly beneficial effects
      on systemic and renal hemodynamics, as well as on left ventricular and aortic
      masses, without any effect on coronary hemodynamics. These effects of omapatrilat
      on arterial pressure and aortic mass, but not on renal hemodynamics and left
      ventricular mass, may have been at least partially mediated through the action of
      bradykinin.

PMID- 12808491
TI  - [A descriptive study of intrahospital neurology service consultations].
AB  - INTRODUCTION: Neurology consultations requested by other services are a part of
      hospital attention that has not been studied or valued enough. However, it is a
      health care activity that is carried out on a daily basis and which consumes
      considerable amounts of time and resources. AIMS. The aim of this study is to
      assess intrahospital consultations (IHC) requested from a Neurology service.
      PATIENTS AND METHODS: We conducted a retrospective study of the requests for
      consultations received in the Neurology Service at the Hospital Universitario San
      Cecilio in Granada throughout the year 2001. The following variables were
      analysed: number of consultations, specialities involved, urgency of the request,
      syndromic diagnosis, complementary tests requested, final resolution and referral
      of patients. RESULTS: The number of consultations amounted to 270. The most
      frequent syndromic diagnoses were stroke (24.3%), epilepsy (13.7%) and dementia
      (11.7%). Internal Medicine, Cardiology, Vascular surgery and Oncology were the
      specialities that requested most consultations from the Neurology service. The
      most common complementary test was a computerised axial tomography of the head.
      38.74% of the consultations were referred to Neurology outpatients for follow up.
      40.5% of the consultations received were lacking in the information needed to
      understand the actual problem the patient was suffering from. CONCLUSIONS: This
      study attempts to highlight the importance of IHC as part of the day to day
      activity within a Neurology service, with respect to the number of consultations,
      knowledge of the most prevalent neurological pathologies in other services and
      the resources used in this type of assistance. More studies are needed on this
      subject, since there are few references in the literature to reports that analyse
      this type of attention.

PMID- 12808492
TI  - [Neuronal DNA damage correlates with a positive detection of c-Jun, nuclear
      factor kB, p53 and Par-4 transcription factors in Alzheimer's disease].
AB  - INTRODUCTION AND OBJECTIVES: Alzheimer s disease is a neurodegenerative disorder
      characterized neuropathologically by beta amyloid plaques, neurofibrillary
      tangles, gliosis and neuronal loss. Recently, we have elucidated a molecular
      cascade of cell death induced by A beta 25 35 involving the activation of nuclear
      factor kappa B (NF kB), p53, and c Jun transcription factors in vitro. At
      present, no comparative reports have been published to establish a similar cell
      death signalization pathway in in vitro and in in vivo. The aim of this
      investigation was to determine if AD brains might activate NF kB, p53, c Jun, Par
      4 transcription factors and to establish whether there exist a relationship
      between neuronal DNA damage and transcription factors activation. PATIENTS AND
      METHODS: We investigated Ab plaques, neurofibrillary tangles and NF kB, p53, and
      c Jun transcription factor activation in five cerebral regions from 3 normal
      subjects and from six demented patient with sporadic AD and one patient with AD
      familiar according to CERAD criteria. Using TUNEL we determine neuronal damage.
      RESULTS: We demonstrated neuronal damage in 17 out of 50 regions evaluated as
      TUNEL positive, and their distribution was heterogeneous in all brain regions
      evaluated; and the activation of NF kB, p53, c Jun and Par 4 transcription
      factors from case # 24 and #22, corresponding to TUNEL positive. CONCLUSIONS: We
      found a correlation between severity of DNA damage and nuclear activation of the
      transcription factors. These findings suggest that the AD brain may induce cell
      death by a molecular signalization similar to a non neuronal model by Ab
      exposure. This in situ study might validate previous Ab induced cell death
      observations in vitro.

PMID- 12808493
TI  - [S100 protein in tumours of the central nervous system].
AB  - OBJECTIVE: S100 protein has been detected in glials cells. The subject of this
      study is to evaluate the usefulness of serum levels of S100 as tumor marker for
      the screening diagnosis and follow up in patients with CNS tumors. PATIENTS AND
      METHODS: 57 patients were studied with tumors of the CNS: 24 multiform
      glioblastomas (GM), 11 anaplastic astrocytomas (AA), 3 oligodedrogliomas, 1
      pinealoblastoma, 3 neurinomas, 1 low grade glioma and 13 brain metastasis of
      other extraneural primary tumors. 25 healthy people have been taken as control
      group. The S100 was analyzed by an immunoradiometric assay (IRMA) with 125 Iode.
      The cut off value was 0.2 g/L. RESULTS: The presurgical mean serum values of S100
      didn t differ of the mean values of the control group (0.08 and 0.07 g/L,
      respectively). In the surgical treated patients with residual tumoral or
      recurrent tumors, the values of S100 increases to 38.9% in GM, 57.11% in AA and
      76.9% in brain metastasis. In GM the serum values are significantly higher in
      patients with active tumor before receiving treatment with chemotherapy,
      radiotherapy or radiosurgery (p < 0.05). The values decreses to normal levels
      after response to oncological therapies. During the follow up (mean 551 days),
      the global sensitivity of S100 for progression of the disease was 47.5% and
      specificity was 90% with a correspondence between S100 and disease s evolution of
      56%. CONCLUSIONS: S100 protein is not useful in the initial diagnosis of tumoral
      disease but it could be of help in the follow up of the disease because it
      decreases with successful treatments and increases at the time when the tumor
      progress.

PMID- 12808495
TI  - [Multiple sclerosis in Mexico: a multicentre study].
AB  - INTRODUCTION: Multiple sclerosis (MS) is considered to be a low prevalence
      disease in Mexico; its characteristics have been described in isolated studies in
      small populations concentrated in a single region of the country and using
      heterogeneous methodological tools. AIMS. In this study, our aim was define the
      clinical profile and some socio demographic aspects of MS in Mexico using
      validated homogeneous criteria and tools. PATIENTS AND METHODS: Eight hospitals
      representing the five most densely populated regions of the country, the north,
      centre and south of Mexico, took part in the study. Data were obtained through a
      survey created, validated and published in Spanish (k interobserver 0.73 and k
      intraobserver 0.76), which consisted of 142 questions arranged in 10 sections and
      which was applied by 12 neurologists. The procedure was verified with 50 randomly
      selected surveys. A total of 337 surveys were applied, which were analysed by
      descriptive statistics using the EPI INFO, version 6.04b, software application.
      All the patients presented MS that had been clinically defined with the help of
      paraclinical studies according to Schumaher and Poser's criteria. RESULTS: A
      sample of 337 patients was studied; 99.1% were mestizos, with an average age of
      37 9 years, 69.7% were females and 30.3% males. 95% had access to the Social
      Security system and 96% had been born in Mexico to Mexican parents. No cases were
      found among native Mexicans. The clinical profile of the disease did not differ
      to that reported in other countries; the pattern observed corresponded to that
      found in northern latitudes. CONCLUSION: This is the first multicentre study
      carried out in Mexico with a population that is highly representative of the
      whole country and with a homogeneous methodology.

PMID- 12808494
TI  - [Specific alterations in attention in the early stages of Parkinson's disease].
AB  - INTRODUCTION: The cognitive disorders presented by patients with Parkinson s
      disease (PD) have drawn attention to the role played by the basal ganglia in
      cognition. It has been suggested that through a system of cortico subcortical
      circuits they monitor the work done by the frontal regions by guiding the
      anterior and posterior attentional systems, whose functioning is necessary for
      the so called executive functions to be carried out. PATIENTS AND METHODS: We
      studied 10 patients with PD in developmental stages I and II according to the
      scale of Hoehn and Yahr, and 10 healthy paired controls. All of them were
      administered a test for simple sustained attention, complex sustained attention
      and attentional shift. RESULTS: In the simple sustained attention task there were
      no significant differences between groups. In the complex sustained attention
      test the patients committed more mistakes, and in the attentional shift task they
      committed more omissions and there was a significant increase in reaction time.
      CONCLUSIONS: Even in the early stages of the disease, patients suffering from
      Parkinson present cognitive disorders. These are concentrated in the detection
      and evaluation of new information, in the capability to shift attention between
      different spatial regions in a flexible manner and in choosing, inhibiting and
      activating motor programmes. In order to detect these alterations more sensitive
      and complex tests must be used.

PMID- 12808496
TI  - [Peculiarities of the parietal organisation of the superficial temporal artery].
AB  - INTRODUCTION: The study of the structure in the arterial wall has been essential
      to use vessels in the coronary and cerebral bypass. The superficial temporal
      artery, owing to its high elastic content and its topography, close to the middle
      cerebral artery, has made possible the revascularization surgery in cerebral
      areas with ischemia. AIM. The purpose of this study is define the structure of
      the superficial temporal artery. MATERIAL AND METHODS: The material of the
      present study are 60 arteries from medico legal necropsies without apparent
      vascular pathology. Pieces were fixed in 10% formol, embedded in Paraplast,
      sectioned in sequence of 7 mm and were stained to detect elastic, collagen and
      reticulin fibers. Histochemical techniques have been done too. RESULTS: The
      superficial temporal artery shows a high elastic content, above all in the middle
      outer of the tunica media. The negative aspect is the great quantity of collagen
      in this tunica, that produces the progressive hardness of this vessel with the
      increase of the age. Histochemistry shows how the accumulation of acid
      mucosubstances interferes in the correct nourishing of the internal elastic
      membrane, that is disorganized in the cushions. CONCLUSION: The superficial
      temporal artery is an appropriate vessel to the coronary and cerebral bypass, due
      to its high elastic content in this tunica and the limitants. It have not been
      observed in our material zones without internal elastic membrane. Histochemistry
      shows abundant acid mucosubstances that difficult the nourishing in the arterial
      wall.

PMID- 12808497
TI  - [Multiple symmetric lipomatosis associated to polyneuropathology, atrophy of the
      cerebellum and mitochondrial cytopathy].
AB  - INTRODUCTION: Multiple symmetric lipomatosis (MSL), which is predominantly found
      in middle aged males, is characterised by accumulations of fat in the neck,
      shoulders and other parts of the trunk, and sometimes associated with different
      neurological manifestations, both central and peripheral. Although its aetiology
      is unknown, it has been described as associated with mitochondrial cytopathies.
      AIMS. To describe the case of a young female with MSL associated with
      mitochondrial encephalomyopathy. CASE REPORT: Girl aged 14 with MSL, ataxia,
      patellar hyperreflexia, bilateral Babinski sign, pes cavus, axonal peripheral
      neuropathy, involvement of the optic pathway, atrophy of the cerebellum,
      subsarcolemmal mitochondrial accumulations in the untrastructural examination of
      the vastus lateralis muscle and partial deficit of complex I in the mitochondrial
      respiratory chain. As regards molecular genetic aspects, the most frequent
      mutations of the ATPase 6 gene in lymphocytes, and mtDNA deletions and tRNALys
      and tRNALeu(UUR) mutations in muscles were excluded. CONCLUSIONS: Despite the
      fact that MSL is an entity normally found in adults, the possibility of its being
      diagnosed in the paediatric age must be taken into account. This case is probably
      the second time MSL has been observed associated with mitochondrial cytopathy in
      this age bracket.

PMID- 12808498
TI  - [Zellweger syndrome. Reports on two new cases].
AB  - INTRODUCTION: Zellweger syndrome, or cerebrohepatorenal syndrome, is the most
      serious form of the peroxisomal diseases. Clinically, it is characterised by the
      association between craniofacial dysmorphia and neurological disorders, together
      with the involvement of other organs. To perform a diagnosis it is advisable to
      follow a procedural protocol that begins with the quantification of very long
      chain fatty acids in an assortment of samples (serum, fibroblasts and
      mononucleate cells), plasmalogens, branched chain fatty acids in serum (phytanic
      and pristanic acids), polyunsaturated acids and bile salts. Studies conducted
      with neuroimaging, renal echography, skeletal X rays and biopsy samples of
      different tissues will provide us with information about the involvement of
      different organs. CASE REPORTS: The first case we report is that of a male who,
      from birth, presented a distinctive phenotype with very large fontanelles,
      important hypotonia, epileptic seizures and acute organic disorders that led to
      death at the age of seven weeks. The second case involved a new born male
      suffering from prenatally diagnosed heart disease and craniofacial dysmorphia
      with hypotonia. CONCLUSIONS: Given the scarce survival rate of patients, early
      diagnosis of this type of disease is crucial and, although complex, a study must
      be conducted so as to be able to provide genetic counselling.

PMID- 12808499
TI  - [Foreign language syndrome as a first sign of multiple sclerosis].
AB  - INTRODUCTION: Foreign accent syndrome (FAS) is a little known disorder affecting
      language which has been described in a few cases after acute strokes or traumatic
      brain injuries, but until now has not been reported in multiple sclerosis (MS).
      It is characterised by the appearance of what is perceived to be a foreign accent
      in the language of the patient. Although it could be included within the
      dysprosodias that accompany motor aphasias, it should be considered as an entity
      in its own right, since it may appear without the accompanying aphasia. Aphasia
      is an infrequent manifestation of MS and even less so when it appears as an
      initial symptom of the disease. When it does occur it usually accompanies large
      demyelinating lesions in the dominant hemisphere, and it is usually of a motor
      type. CASE REPORT: Patient, aged 38 years, who presented FAS that accompanied
      mild non fluent aphasia as the first manifestation of MS with pseudotumoral
      lesions. Initially the clinical features were interpreted as a somatoform
      disorder, which delayed diagnosis. CONCLUSIONS: Like aphasia, FAS can occur in MS
      as a manifestation of a cortical language disorder. It is important to recognise
      this in order to prevent mistaken diagnoses.

PMID- 12808500
TI  - [Acute myelopathy in a diver caused by decompression sickness. A case description
      and a survey of the literature].
AB  - INTRODUCTION: Decompression sickness (DS) is caused when bubbles of an inert gas
      usually nitrogen, since oxygen is metabolised in the tissues are released into
      the bloodstream and tissues during fast ascents once the atmospheric pressure is
      lowered near the surface. Neurological complications are its most serious form of
      expression and include vertigo, headache, stroke and acute myelopathy, among
      others. DS that affects the spinal cord is infrequent. CASE REPORT: A male, 42
      years old, who presented progressive tetraparesis 15 minutes after returning to
      the surface following several immersions up to 40 metres deep in the same day.
      Neurological exploration revealed tetraparesis that was predominantly distal and
      in the lower limbs, a posterior cord syndrome, urinary incontinence and
      neurogenic pain. Total column magnetic resonance imaging showed areas of diffused
      hypersignal in the T2 sequence in the thoracic and cervical (C2 to C6) regions,
      predominating in the posterior cords. The echocardiogram, transcranial Doppler
      and spirometric studies ruled out an arterial gas embolism following pulmonary
      barotrauma. CONCLUSIONS: Spinal DS can give rise to a serious myelopathy, which
      affects the pyramidal pathway, posterior cords and sphincteral control, and which
      generally appears after sudden ascents from the deep dives.

PMID- 12808501
TI  - [Progressive encephalopathy with oedema, hypsarrhythmia and optic atrophy (PEHO
      syndrome). A case report].
AB  - INTRODUCTION: Progressive encephalopathy with oedema, hypsarrhythmia and optic
      atrophy (PEHO syndrome) is a pathological process that begins in the first months
      of life and quickly leads to a very serious encephalopathy. We report the case of
      an infant suffering from PEHO syndrome and discuss its pathogenesis. CASE REPORT:
      A 4 year old male, the son of parents who were not blood related, with no pre or
      perinatal background of interest, who, from the first month, was seen to have a
      moderate retardation in psychomotor development and generalised hypotonia. These
      clinical signs increased progressively over the next months. From the age of 6
      months onwards infantile spasms were observed, together with an EEG displaying
      hypsarrhythmic characteristics, slight facial oedema as well as in the hands,
      abnormal ocular movements and loss of vision with optic atrophy. In the
      neuroimaging serial studies, MRI showed a progressive atrophy of the brain stem
      and the cerebellum associated with cortical atrophy, hypoplasia of the corpus
      callosum and retarded myelination. CONCLUSIONS: Diagnosis of PEHO syndrome is
      essentially clinical with the help of neuroimaging, since there is no biological
      or genetic marker. The case described fulfils the criteria required for diagnosis
      of PEHO syndrome. The existence of cases in the family suggests that PEHO
      syndrome is due to a genetically based neurodevelopmental disorder. To our
      knowledge this is the first case reported in Spain.

PMID- 12808502
TI  - [Pharmacological targets in neurodegenerative diseases].
AB  - The frequency, morbidity and complexity of neurodegenerative diseases (NDD) make
      them the greatest therapeutic challenge to Medicine today. These diseases are
      characterized by a decreased number of cells in certain neuronal populations,
      which is clinically reflected in the appearance of specific symptoms. In this
      study, we will centre our attention on the two fundamental lines of action that,
      from a pharmacological point of view, are available for the treatment of NDD. The
      first is aetiopathogenic, and is aimed at stopping cell death and promoting the
      recovery of cell populations. The second line is physiopathological and seeks to
      prevent, delay or palliate the appearance of the symptoms indicating an
      alteration in the levels of neurotransmitters, and its chief objective is to
      maintain them. Pharmacology has already provided neurologists with a wide range
      of tried and tested drugs, yet the results obtained in research laboratories in
      the last few years seem to indicate that the number of therapeutic possibilities
      are very likely to rise sharply in the future. Progress made in genomics and the
      better understanding of cellular biochemical cycles allow us to expect that this
      century will finally be that of the Neurosciences, and that Neurology, without
      losing its cognitive essence, will start to be considered to be a speciality that
      is as therapeutic as it is diagnostic.

PMID- 12808503
TI  - [The interest of multiple sclerosis attacks. Physiopathology and therapy].
AB  - AIMS: To review the clinical concept of an attack, the physiopathological
      mechanisms underlying the symptoms of the attack, in the recovery phase, and
      those corresponding to the progressive or degenerative phase of the disease.
      DEVELOPMENT: Although they do not explain the exact mechanisms responsible for
      the onset of the attack or the processes that account for the clinical and
      pathological heterogeneity, most research studies suggest that the lesions
      produced in multiple sclerosis are the consequence of complex immunological
      interactions that take place mostly in the white matter of the central nervous
      system. These lesions affect, to variable extents, the myelin and the axon. We
      survey how these events are reflected in the images obtained by magnetic
      resonance. Clinical observations have shown that, in some patients, infections
      and hormones can exert an influence on the activity of the disease. Recovery, in
      the initial stages at least, would be produced by the action of poorly understood
      mechanisms that limit inflammation, and by local or cortical neuroplasticity or
      repair processes. Finally, we discuss the mechanisms behind the action of
      corticoids that justify their use when treating these attacks. CONCLUSION: A more
      thorough understanding of these events opens up the way to providing better
      therapy in the future.

PMID- 12808504
TI  - [Sphincter function disorders. physiopathology and neurophysiological study].
AB  - Miction and defecation disturbances are very frequent in the general population
      and far more so among neurological patients. It is essential to know the
      physiopathology of these disorders in clinical practice. The neurological control
      of these functions is carried out by automatisms that are regulated in the nuclei
      of the brain stem through somatic and vegetative peripheral structures that act
      simultaneously. The cortical, hypothalamic and reticular levels play a part in
      the activation or inhibition of the pontine nuclei. Continence depends on the
      integrity of the anatomical structures and the sensory, pressure and mechanical
      systems that enable the automatisms to develop. Neurological examination must be
      combined with studies conducted by other specialists on patients in which no
      neurological illness is known, but who have this kind of dysfunction. Adding a
      neurophysiological examination allows us to complete the clinical study and to
      check objectively for the existence of external anal sphincter denervation or
      disorders involving the exteroceptive reflexes of the sacrum. The recent
      appearance of techniques for treating incontinence that make use of the repeated
      and continuous stimulation of the sacral roots has revolutionised the way these
      patients are treated and calls for greater involvement of neurologists in dealing
      with these problems.

PMID- 12808505
TI  - [Ex vivo gene therapy in the treatment of Parkinson s disease].
AB  - OBJECTIVE: Taking into account the growing development and application of in vivo
      and ex vivo gene therapy in neurodegenerative disorders we review this kind of
      therapy applications in Parkinson s disease. DEVELOPMENT: Gene therapy carried
      out to this illness includes the liberation of genes encoding biosynthetic
      enzymes for dopamine synthesis: tyrosine hydroxylase, AADC and GTP cyclohydrolase
      and neurotrophic factors like GDNF which promotes the survival and maintenance of
      dopamin rgic neurons. Ex vivo gene therapy allows the control of the gene
      transfer before implantation, however one of the fundamental problems of this
      procedure is given by the immunologic rejection, so the use of autologous sources
      is recommended. CONCLUSIONS: Ex vivo gene therapy is advantageous in relation to
      in vivo gene therapy because it allows the control of gene transfer before the
      implantation; looking for cellular sources of neural origin or pluripotent stem
      cells which can be differenciated toward a wanted cellular type in order to
      achieve the structural and functional integration of the cells implanted in the
      central nervous system are recommended; however it becomes necessary the
      development of vectors of new generation to avoid biosafety problems involved in
      the gene therapy.

PMID- 12808506
TI  - [The neurobiology of developmental dyslexia: a survey].
AB  - One of the most common disorders affecting the ability to read is developmental
      dyslexia, which, unlike the alexia related to a loss of the capacity to read
      associated with brain damage, refers to a specific disorder in the acquisition of
      reading skills and becomes apparent in reiterated persistent difficulties in
      learning to read. A number of studies have attempted to detect structural and
      functional abnormalities that might be the origin of problems in learning to
      read. The use of functional neuroimaging techniques such as positron emission
      tomography (PET), spectroscopic magnetic resonance imaging (SMRI) and functional
      magnetic resonance imaging (fMRI) enables us to measure changes in the metabolic
      activity associated with alterations in the neuronal networks involved in the
      reading process. In this review, different studies are analysed in an attempt to
      identify alterations in the cortico subcortical regions which could be the origin
      of the developmental dyslexia. Results show that in dyslexics there is a
      temporoparietooccipital disconnection, and a disconnection with the left frontal
      cortex as regards the demands for fast auditory processing, as well as
      abnormalities in the connections between the temporoparietal cortex and the
      cerebellum with other regions of the brain. Such findings suggest that the
      altered areas of the brain do not only show a characteristic pattern of
      hypoactivation, but also that these alterations could be the cause of this
      malady. We highlight the importance of these findings in the diagnosis and
      rehabilitation of this population.

PMID- 12808507
TI  - [Towards a taxonomy of consciousness].
AB  - INTRODUCTION: There are many definitions in order to describe the consciousness.
      In the literature appear concepts such alertness, attention, knowledge, conscious
      experience, awareness of deficits, self awareness, theory of mind in relation
      with consciousness definition. This multiplicity conceptual lead to formulate a
      question: Do exist different levels of complexity in the consciousness that
      depend on neuroanatomics structures differentiated? METHOD: In this paper an
      approximation toward a taxonomy of consciousness is offered and five levels of
      complexity and its relation with cerebral structures differentiated are
      suggested. In the first place, it s consider the alertness state as a necessary
      condition to exist the consciousness and his relation with attentional states. In
      the second place, it s present the conscious experience that depends on
      synchronicity neural activity. On the other hand, the daily clinic work shows the
      possibility of the existence of a consciousness for each specific field of
      knowledge. In the fourth place, it s located the self awareness understood like
      the capacity to perceive to us with objectivity but maintaining a subjectivity
      sense. At last, the theory of mind refers to the ability for attribute to the
      others specific mental states. CONCLUSION: It s plan an analysis of the different
      models that have tried to give an answer to each one of complexity levels to
      attempt an approach based on the analytic science and not descriptive plane.

PMID- 12808510
TI  - Agencies and acronyms: a guide to regulatory jargon.
AB  - This article highlights a table listing acronyms frequently encountered in
      perianesthesia and ambulatory surgery settings. Agencies, regulations,
      legislative acts, organizations, and more are provided along with contact
      information and brief comments. The resource guide is printed with changes with
      the permission of its author, Mrs. Jerry Henderson, and the American Association
      of Ambulatory Surgery Centers.

PMID- 12808511
TI  - Accreditation: a "voluntary" regulatory requirement.
AB  - Hospitals and ambulatory surgery centers may choose to voluntarily apply for
      accreditation from the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO), the Accreditation Association for Ambulatory Health Care
      (AAAHC), or the American Association for the Accreditation of Ambulatory Surgical
      Facilities (AAAASF) as appropriate. The facilities must comply with written
      standards regarding the environment of care, the provision of care, and the
      quality of care. Regular surveys of the organization's performance by the
      accrediting agency are intended to ensure the quality of care provided to the
      patients entrusted to our care. The accreditation process certifies to the health
      care community and the community-at-large that the facilities meet nationally
      accepted standards through a recognized accreditation program. Perianesthesia
      nurses should have an understanding of the regulatory agencies that influence
      daily patient care. This article provides an overview of the 3 accrediting
      bodies: JCAHO, AAAHC, and AAAASF. These agencies are committed to improving
      safety by providing standards of care, survey evaluations, and professional
      consultative and educational services, and they have an important role in our
      health care environments.

PMID- 12808512
TI  - The professional nurse and regulation.
AB  - The regulation of nursing began as a simple registry process to protect the
      nursing title and the public. Today, the primary purpose is still the protection
      of the public through defining nursing practice, approving nursing education, and
      overseeing the competence of nurses through licensing and disciplinary rules and
      regulations. State Boards of Nursing are legislatively given the authority to
      license and discipline the nursing profession. The RN is responsible for the care
      given to assigned patients. Issues of staffing, delegation, and reporting of
      incompetent or impaired nurses are a concern of nurses today with regard to their
      license. Each nurse must understand the regulations, which vary from state to
      state, that directly and indirectly affect his/her daily practice. As the health
      care environment is met with several challenges, pressures are increasing to
      modernize the licensing and competency assessment of nurses. Ultimately, the
      safety of patients must remain at the center of the regulatory debate.

PMID- 12808513
TI  - Standards of perianesthesia nursing practice: advocating patient safety.
AB  - The practice continuum of perianesthesia nursing interacts in concert with other
      nursing and medical professional organizations. Professional standards of care
      establish frameworks that guide these practitioners in the delivery of care.
      ASPAN is charged with the ethical responsibility of defining and promulgating
      minimum standards of perianesthesia nursing practice. This article discusses the
      various definitions and uses of standards, as well as the vital importance of
      using ASPAN Standards. How standards differ from position statements, laws, and
      regulations, and how standards advocate for patient safety and protect the nurses
      in their specialty practice are also discussed. In addition, case scenarios will
      be presented to show how the American Society of Anesthesiologists' (ASA)
      standards play a major role in the surgical patient's care.

PMID- 12808514
TI  - Regulatory compliance in the ambulatory surgery setting: a process improvement
      approach.
AB  - Keeping up with the many rules and regulations associated with health care can be
      a challenge in these times of constantly increasing and changing local, state,
      federal, and accreditation agency regulations. The task can be made simpler by
      using a quality improvement process to track and enhance performance and
      compliance. This article focuses on the development of a plan that not only
      tracks requirements, but also provides the format for process change and
      improvement. The process is designed for use in the ambulatory surgery setting,
      although certain ideas and processes can be applied in the hospital setting as
      well. The process can and should ensure that the unit or facility is doing the
      "right thing" for team members, patients, and visitors.

PMID- 12808515
TI  - Understanding and complying with HIPAA.
AB  - The Health Insurance Portability & Accountability Act (HIPAA) has required health
      care organizations to make significant changes to operations to comply with
      federal regulations for Privacy and Electronic Transactions. This article
      provides a brief history and overview of the law, its implications for nurses,
      the consequences of noncompliance with the law, and where to find informational
      resources.

PMID- 12808516
TI  - The basics of an exposure control plan.
AB  - Prevention and control of employee injury and exposure begins with an
      organizational commitment to provide a safe work environment for the employees.
      An Exposure Control Plan (ECP) helps to ensure this safe environment, and is
      developed by an organization and administered to provide for the elimination and
      minimization of occupational exposure to blood-borne pathogens, which is one of
      the greatest areas of risk for the health care provider. The Occupational Safety
      and Health Administration (OSHA) standard 29 CFR 1010.1030, "Occupational
      Exposure to Bloodborne Pathogens," outlines the requirements necessary to meet
      compliance as an institution. However, occupational exposure requirements have
      changed over the last few years and now incorporate practice advances regarding
      safety devices (ie, needleless and protected) and their use and implementation.
      Directives addressing the management of the employee who has been exposed to
      blood-borne pathogens have also been added. This article focuses on important
      elements in developing an institutional exposure control plan.

PMID- 12808517
TI  - Perianesthesia medication administration: can we be too careful?

PMID- 12808518
TI  - Preventing medical errors in the perianesthesia setting.

PMID- 12808519
TI  - The advanced directive: a fundamental communication.

PMID- 12808520
TI  - Research and regulatory actions: a continuing circle of events.

PMID- 12808522
TI  - Peer review: is it for you?

PMID- 12808527
TI  - Outpatient cognitive behavioral pain management programs: a randomized comparison
      of a group-based multidisciplinary versus an individual therapy model.
AB  - OBJECTIVE: To compare the efficacy of 2 models of chronic pain management.
      DESIGN: Randomized comparative trial with 2 active treatment arms. SETTING:
      Outpatient pain management clinics. PARTICIPANTS: A total of 113 adults with
      chronic pain of 0.5 to 38 years duration in (mean, 8.8y). INTERVENTIONS:
      Cognitive behavioral therapy (including education, relaxation, use of cognitive
      coping strategies, pacing, exercise) delivered in group-based multidisciplinary
      program or in an individual therapy program. MAIN OUTCOME MEASURES: Self-report
      of interference with daily activities and sense of control over pain (West Haven
      Yale Multidimensional Pain Inventory [WHYMPI]) and depression (Beck Depression
      Inventory). Secondary outcome measures were state anxiety (Spielberger State
      Trait Anxiety conventory), analgesic medication consumption, general activity,
      and pain severity (WHYMPI). Measurement points were 0 (before treatment), 2
      months (end of treatment), and 3, 6 and 12 months (follow-up). RESULTS: No
      significant differences were found between the 2 modes of treatment at any of the
      major time points (0, 2, 12mo). Both treatment conditions made significant and
      sustained improvements on all primary outcome measures, although sense of control
      over pain tended to decline by 1 year. Individually treated participants made
      slower gains in some areas, but showed a lesser tendency to rebound at the end of
      treatment. CONCLUSION: The 2 programs appear to be equally efficacious for pain
      management in adults with chronic pain. In practical terms, the choice of model
      for service provision may rest more on local issues such as the availability of
      space and staff time.

PMID- 12808528
TI  - Pain characteristics in patients admitted to hospital with complications after
      spinal cord injury.
AB  - OBJECTIVES: To determine characteristics of pain, the relation between pain and
      mood, the effect of pain on activities, and the perceived difficulty in coping
      with pain in patients hospitalized for treatment of complications associated with
      spinal cord injury (SCI). DESIGN: Cohort survey. SETTING: Hospital inpatient unit
      in Australia. PARTICIPANTS: Consecutive sample of patients (N=88) admitted to a
      hospital spinal injuries unit with complications after SCI. Two eligible patients
      declined to participate. INTERVENTION: Face-to-face interview with questionnaire.
      MAIN OUTCOME MEASURES: Pain severity, global self-rated health, mood (Kessler
      Mood Inventory), and interference with activities (Von Korff disability scale).
      RESULTS: Sixty-six (75%) of the 88 subjects experienced pain, with an average
      time of onset +/- standard deviation of 8.02+/-12.4 years; 27% of those with pain
      described it as severe or excruciating. Subjects with pain were less likely to
      rate their global health as excellent or very good when compared with those who
      did not have pain (22% vs 44%, respectively). Patients with pain had
      significantly greater levels of psychologic distress than did people with SCI and
      no pain. CONCLUSIONS: Pain is a common problem in people admitted to hospital
      with SCI for treatment of other complications. It has a significant impact on
      activities and is associated with a reduction in global self-rated health and
      higher levels of psychologic distress.

PMID- 12808529
TI  - Use of behavioral contingencies to promote prevention of recurrent pressure
      ulcers.
AB  - OBJECTIVE: To determine effectiveness of an intervention using monetary rewards
      as a consequence for preventing or reducing severity of pressure ulcers in spinal
      cord injury (SCI) patients with a history of chronic, recurrent ulcers. DESIGN:
      Multiple baseline analysis across subjects (time-lagged control), comparing
      severity of pressure ulcers and treatment costs during baseline and intervention.
      SETTING: Outpatient wound-care clinic of private, nonprofit specialty hospital.
      PARTICIPANTS: Nine adults (all with paraplegia) with a history of
      hospitalizations for treatment of pressure ulcers. INTERVENTIONS: In study 1,
      participants (n=6) undertook (1) a comprehensive self-care plan, (2) had a
      graduated schedule of visits with an advanced practice nurse, and (3) received
      monetary rewards for successfully preventing serious ulcers. In study 2,
      participants (n=3) undertook interventions 1 and 2, but monetary rewards were in
      staged phases so a component analysis could compare the effectiveness of visits
      alone to visits plus monetary rewards. MAIN OUTCOME MEASURES: Severity of
      pressure ulcers measured with the Pressure Ulcer Scale for Healing (PUSH Tool
      3.0); and direct costs of treatment and preventive care for pressure ulcers.
      RESULTS: In study 1, severity of pressure ulcers-and their related treatment
      costs-decreased for the 6 participants. Maintenance of effects postintervention
      was highly variable, with only 3 participants showing long-term improvements. In
      study 2, for 2 participants, visits alone did not reduce pressure ulcer severity,
      but visits plus payments did effectively reduce ulcer severity, indicating
      improved prevention behaviors. CONCLUSIONS: Findings support the assumption that
      pressure ulcers may recur among some individuals because there are insufficient
      positive consequences for effective prevention.

PMID- 12808530
TI  - Physical, mental, and social predictors of functional outcome in unilateral lower
      limb amputees.
AB  - OBJECTIVE: To study the value of physical, mental, and social characteristics as
      predictors of functional outcome of elderly amputees. DESIGN: Prospective,
      inception cohort study; comparisons with reference populations. SETTING: Main
      hospitals, rehabilitation centers, nursing homes, patients' own residence
      settings in 1 of the 3 northern provinces in the Netherlands. PARTICIPANTS: Forty
      six patients older than 60 years, with unilateral transtibial or transfemoral
      amputation or knee disarticulation because of vascular disease. INTERVENTIONS:
      Measurement of physical, mental, and social predictors 2 and 6 weeks
      postamputation. MAIN OUTCOME MEASURES: The Sickness Impact Profile (SIP-68),
      Groningen Activity Restriction Scale (GARS), Timed up and go (TUG) test, and
      prosthetic use. RESULTS: A total of 15% of amputees died within the first year
      after amputation. Seventy percent lived independently at home 1 year
      postamputation. The functional level of the patients was low, as shown by high
      scores on the SIP-68 (mean, 23.6), GARS (mean, 41.2), and TUG test (mean, 23.9s).
      Functionally effective prosthetic use, as measured with the classification of
      Narang and Pohjolainen, was reached by 49%. For the SIP-68 scores, age,
      comorbidity, 1-leg balance, and the 15-word test predicted functional outcome in
      69% of amputees. For the GARS score, age, 1-leg balance, and the 15-word test
      predicted functional outcome in 64%. For the TUG test, age and 1-leg balance
      predicted functional outcome in 42% of amputees. After correction for age, the
      only significant predictor for prosthetic use was 1-leg balance. CONCLUSIONS:
      Elderly patients with a leg amputation had a low functional level 1-year
      postamputation. An important part of functional outcome could be predicted 2
      weeks after amputation by age at amputation, 1-leg balance on the unaffected
      limb, and cognitive impairment. Severe comorbidity probably also played a role.
      The results may be used in the general policy concerning leg amputees.

PMID- 12808531
TI  - Classification of shoulder complaints in general practice by means of nonmetric
      multidimensional scaling.
AB  - OBJECTIVES: To determine if a classification of shoulder complaints in general
      practice can be made from variables of medical history and physical examination
      with nonmetric multidimensional scaling and to investigate the reproducibility of
      results from an earlier hierarchical cluster analysis. DESIGN: A classification
      study performed using nonmetric multidimensional scaling. SETTING: Four general
      practices in the Netherlands. PARTICIPANTS: Ninety-eight consecutive patients
      presenting with shoulder complaints in general practice were examined at study
      entry and after 2 weeks of treatment. INTERVENTION: All patients were treated
      with a nonsteroidal anti-inflammatory drug during the first 2 weeks of treatment.
      MAIN OUTCOME MEASURES: Eleven variables of the medical history and 19 variables
      of the physical examination were used in a nonmetric multidimensional scaling
      analysis. RESULTS: The analysis of the data at inclusion as well after 2 weeks
      shows that a 1-dimensional configuration can be used to represent the shoulder
      complaints. The results of the cluster analysis are consistent with the results
      of the nonmetric multidimensional scaling. The degree of limitation in range of
      motion and the degree of pain felt by the patients together determine the
      position of the patients on the dimension. CONCLUSIONS: The analysis shows that
      detailed classifications for the diagnosis of patients with shoulder complaints
      in general practice cannot be confirmed by empirical data available to the
      general practitioner. The results confirmed the recommendations of the new Dutch
      Guidelines for Shoulder Complaints, issued in 1999.

PMID- 12808532
TI  - Practical problems and management of seating through the clinical stages of
      Duchenne's muscular dystrophy.
AB  - OBJECTIVE: To describe seating problems in patients with Duchenne's muscular
      dystrophy (DMD), for the purpose of identifying management solutions that are
      practicable for both patient and caregiver. DESIGN: Case series. SETTING: A
      Japanese long-term care facility. PARTICIPANTS: Ninety-five patients with DMD
      (mean age, 15.9+/-4.4y; Swinyard stages: stage 5, n=17; stage 6, n=24; stage 7,
      n=33; stage 8, n=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Spinal deformity types, frequency and sites of pain, wheelchair propulsive
      ability, activities of daily living, and caregiving-related problems. RESULTS:
      Thirty-three percent of the patients belonged to the early straight group, 21% to
      the scoliotic group, 20% to the kyphoscoliotic group, 2% to the kyphotic group,
      and 24% to the extended spine group. The percentage needing support for sitting
      was higher in patients with spinal deformities (76% vs 0%, P<.05). Forty-one
      percent had pressure problems, and the percentage increased with advancing
      stages, with pain sites related to spinal deformity types. Self-feeding was
      difficult in 10 patients having spinal deformities. Four patterns of manual
      wheelchair propulsion were observed: upper extremity, anteroposterior trunk
      flexion, lateral trunk flexion, and wrist-hand patterns; and propulsion became
      increasingly less practical in this order. For toileting, more patients were
      cared for on wheelchairs with backrests reclined with stage progression. Of 60
      caregivers, 58% experienced trauma related to seating systems. CONCLUSION: The
      seating problems that were identified enabled specific, practical suggestions to
      be made for better management.

PMID- 12808533
TI  - Overwork weakness in Charcot-Marie-Tooth disease.
AB  - OBJECTIVE: To determine the incidence of overwork weakness in Charcot-Marie-Tooth
      disease (CMT). DESIGN: Prospective survey. SETTING: Rehabilitation department for
      CMT in an Italian tertiary care hospital. PARTICIPANTS: A total of 106
      outpatients with CMT, selected for absence of other causes of weakness (age
      range, 11-69y), and 48 healthy volunteers (controls). INTERVENTIONS: The strength
      of 2 intrinsic hand muscles (abductor pollicis brevis [APB], first dorsal
      interosseous) in the dominant and nondominant hands was graded by using manual
      muscle testing and a modified Medical Research Council (MRC) Scale. MAIN OUTCOME
      MEASURES: The side of the stronger muscle and the difference in strength between
      the nondominant and dominant muscles. RESULTS: Muscles were stronger on the
      nondominant side in 65.57% of patients versus 1.04% of controls, and on the
      dominant side in .94% of patients versus 84.38% controls. The difference in
      strength for first dorsal interosseous was .51 in patients and -.32 in controls
      (P>.01). The difference in strength for APB was .65 in patients and -.35 in
      controls (P>.01). CONCLUSIONS: CMT muscles in the dominant hand are weaker than
      in the nondominant hand. This may be the result of overwork weakness.

PMID- 12808534
TI  - Quantitative evaluation of reflex and voluntary activity in children with
      spasticity.
AB  - OBJECTIVE: To determine whether increased reflexes are related to functional
      impairment in children with spasticity. DESIGN: Descriptive measurement study.
      SETTING: Rehabilitation department in Poland. PARTICIPANTS: Sixteen able-bodied
      children and 29 children with spasticity. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Measurement of modulation function of knee tendon reflexes by
      isometric knee extension, maximum isometric knee flexion, and extension torques,
      and scoring of ambulation in patients. RESULTS: In able-bodied children, the
      reflex modulation function increased with voluntary knee extension, reached
      maximum at 5% to 20% of voluntary extension, and then decreased. The reflex
      modulation function in patients fell into 2 major categories. In the majority of
      affected limbs, the modulation function was inverse, with maximum reflex response
      at relaxation, and decreased with an increase of voluntary extension. In the
      remaining limbs, the shape of the reflex modulation function was normal, although
      other parameters changed. Isometric torques decreased more in flexion (65%) than
      in extension (39%). A torque decrease was a result of cocontraction more often
      during knee flexion (65%) than in knee extension (24%). The larger the reflexes,
      the more flexion torque decreased and ambulation deteriorated. This pattern
      occurred in patients with inverse modulation function but not in those with
      normal modulation function. The reciprocal inhibition from knee flexors to
      extensors could be affected in patients with inverse modulation function and
      cocontraction during flexion, whereas other mechanisms occurred in other
      patients. CONCLUSIONS: The experimental design has potential as a quantitative
      measure of abnormal control in children with spasticity and can lead to more
      precise treatment selection criteria.

PMID- 12808535
TI  - Quantitative assessment of the stops walking while talking test in the elderly.
AB  - OBJECTIVE: To examine whether trunk sway and walking speed differ between elderly
      "stoppers" and "nonstoppers" during a shorter version of the stops walking while
      talking (SWWT) test-an observational assessment of impaired dual-task performance
      and during a normal walking trial. DESIGN: The original SWWT test was
      administered on the way to the test room (over a distance of 150m). Then,
      subjects were asked to walk 2 trials of 8m while wearing a trunk sway measuring
      device strapped firmly to their lower back. For the first 8-m trial, no questions
      were asked (control trial). During the second 8-m trial, subjects were asked an
      easy question (What is your age?) after walking 2m. SETTING: Long-stay geriatric
      care unit in Switzerland. PARTICIPANTS: Seventeen institutionalized elderly (16
      women, 1 man; mean age, 86.3y; range, 79-93y). Subjects had to be able to walk at
      least 150m and to understand simple questions. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The amplitude of trunk sway angle and angular velocity in
      the forward-backward (pitch) and side-to-side (roll) directions and the duration
      of each trial were compared between the two 8-m walking trials with and without a
      question among subjects who did and did not come to a complete stop. RESULTS: In
      the original SWWT test, 4 persons stopped walking while talking, compared with 8
      persons who stopped in the short (8-m) walking trial when a question was asked.
      Persons who stopped during the 8-m trial when a question was asked had
      significantly longer walking durations (by 19s) and larger trunk roll angular
      displacements (by 5.5 degrees ) during trials, both with and without a question.
      For both stoppers and nonstoppers, duration was longer during the trial when a
      question was asked. CONCLUSION: A fixed and brief walking distance, coupled with
      a single sudden question, provided an effective method of identifying subjects
      who stop walking while talking. These subjects are those who have slower walking
      speeds and more unstable trunk control in the roll plane even under normal
      walking conditions. Our findings support the predictive capabilities of a brief
      SWWT test for the unstable and fall-prone elderly, as well as the usefulness of
      objective trunk sway measures to identify gait instabilities.

PMID- 12808536
TI  - Agonist contractions against electrically stimulated antagonists.
AB  - OBJECTIVE: To assess an exercise program that uses electrically stimulated
      antagonists to resist agonist muscle contractions. DESIGN: In 1 limb,
      electrically stimulated antagonists resisted elbow flexion and extension. In the
      other, stimulation occurred without volitional muscle contraction. SETTING: A
      biomechanics laboratory in Japan. PARTICIPANTS: Twelve men between the ages of 19
      and 24 years. Subjects served as their own controls. INTERVENTION: Subjects
      trained 3 times a week for 12 weeks. Each session consisted of 10 sets of 10
      elbow flexor and extensor contractions. MAIN OUTCOME MEASURES: Isokinetic elbow
      extension and flexion torques. Biceps and triceps brachii cross-sectional areas.
      RESULTS: Elbow extension torques increased (32.85% at 30 degrees/s, 27.20% at 60
      degrees/s, 26.16% at 90 degrees/s; all P<or=.02) over the training period in
      limbs that trained against electrically stimulated antagonists. Control limb
      extension torque increases were smaller (8.52% -14.91%) and did not reach
      statistical significance. Elbow flexion torques improved in both groups, but the
      changes did not reach statistical significance. Cross-sectional areas increased
      in all muscles but were most marked in the antagonist stimulated limbs: triceps
      16.20% versus 4.25% (P=.01) and biceps 16.65% versus 7.00% (P=.005). CONCLUSIONS:
      Exercises that use electrically stimulated antagonist muscles may be effective in
      increasing muscle strength and mass.

PMID- 12808537
TI  - Complications from therapeutic modalities: results of a national survey of
      athletic trainers.
AB  - OBJECTIVE: To understand better the frequency and type of complications
      encountered by athletic trainers. DESIGN: A descriptive questionnaire. SETTING:
      Athletic training facilities at the high school, college, and professional
      levels, as well as physical therapy clinics. PARTICIPANTS: A total of 3012
      certified athletic trainers employed in above-mentioned settings. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Frequency and types of complications
      encountered for different modalities were computed. Primary modality type used
      and frequency of complications in different settings were explored. RESULTS: Of
      the 3012 surveyed, 905 (30%) responded, 26% of whom reported a complication; 362
      total complications were documented. Cryotherapy accounted for 42% of
      complications, with allergic reactions (n=86), burns (n=23), and intolerance/pain
      (n=16) most commonly listed. Electric stimulation accounted for 29% of
      complications, with skin irritation (n=41), burns (n=40), and intolerance/pain
      (n=18) most commonly listed. Therapeutic heat accounted for 22% of complications;
      therapeutic exercise accounted for 7% of complications. CONCLUSIONS: Compared
      with documented complications in the peer-reviewed literature, our survey results
      differed vastly with regard to the complications encountered. This may reflect a
      learning phenomenon, a shift in modality usage, or a general underreporting of
      complications.

PMID- 12808538
TI  - The use of bioelectric impedance analysis to measure fluid compartments in
      subjects with chronic paraplegia.
AB  - OBJECTIVES: To determine the sensitivity and specificity of body mass index (BMI)
      as a surrogate marker of obesity in individuals with chronic paraplegia and to
      validate bioelectric impedance analysis (BIA) as a method of measuring body
      composition in this group. DESIGN: Cross-sectional study. SETTING: University
      hospital. PARTICIPANTS: Convenience sample of 31 subjects with paraplegia (19
      men, 12 women; mean age, 34.2+/-8.8y) and 62 able-bodied control subjects (30
      men, 32 women; mean age, 28.6+/-7.2y). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Total-body water (TBW) by deuterium dilution; extracellular
      water (ECW) by corrected bromide space. Fat-free mass (FFM)=TBW/.732; fat mass
      (FM)=weight-FFM. Single-frequency whole-body and segmental BIA, and
      multifrequency whole-body BIA. RESULTS: BMI had 100% specificity and 20%
      sensitivity in distinguishing obese from nonobese subjects with paraplegia. TBW
      was predicted by using the equation: TBW (inL)=2.11
      0.1age+3.45sex+.34wt+.28(ht(2)/R)-.086sex x wt(r(2)=.95, standard error of the
      estimate [SEE]=1.86L, P<.0001). This equation had 81.8% specificity and 68.4%
      sensitivity. ECW was predicted by using the equation: ECW (in L)=
      .025+1.03sex+.187wt+.0041(ht(2)/X(c)) -.033sex x wt (r(2)=.75, SEE=1.62L,
      P<.0001). Multifrequency BIA offered no greater prediction of TBW or ECW than
      single-frequency BIA. CONCLUSIONS: BMI has excellent specificity but poor
      sensitivity in distinguishing obese from nonobese individuals with paraplegia.
      TBW (and therefore FFM and FM) and ECW can be reasonably well predicted by using
      single-frequency BIA.

PMID- 12808539
TI  - Locked-in syndrome: improvement in the prognosis after an early intensive
      multidisciplinary rehabilitation.
AB  - OBJECTIVE: To evaluate prognosis and recovery in patients with locked-in syndrome
      (LIS) receiving early intensive rehabilitative care. DESIGN: Consecutive sample
      and follow-up for 5 months to 6 years. SETTING: Three rehabilitation centers in
      Italy. PARTICIPANTS: Fourteen patients with LIS who underwent the same treatment
      and subsequently recovered. INTERVENTIONS: Intensive nursing care and intensive
      and early rehabilitative program, including physiotherapy and respiratory,
      swallowing, and speech training. For 4 patients, occupational therapy was
      performed; 4 subjects also had oculomotor training. After discharge,
      rehabilitative maintenance care continued for each patient. MAIN OUTCOME
      MEASURES: Motor recovery according to the Patterson and Grabois classification,
      functional improvement, and mortality rate. RESULTS: A significant motor recovery
      was found in 21% of subjects, within 3 to 6 months of onset of the morbid event;
      complete swallow recovery in 42%; verbal communication in 28%; communication
      through devices in 42%; effective bladder and bowel control in 35%; and good
      breathing patterns in 50%. At follow-up, the mortality rate was 14% and only 2
      complications were reported. CONCLUSIONS: Intensive and early rehabilitation,
      begun within about 1 month of the morbid event, improved the functional recovery
      and reduced the mortality rate, which, as reported in the literature, had been
      60% about 10 years ago. Further studies are necessary to confirm these data.

PMID- 12808540
TI  - Functional measurement of knee joint position sense after anterior cruciate
      ligament reconstruction.
AB  - OBJECTIVE: To examine for differences in joint position sense (JPS) between knees
      with reconstructed anterior cruciate ligaments (ACLs) and uninjured knees by
      using a functional weight-bearing measurement method. DESIGN: Two-way repeated
      measures in a convenience sample. SETTING: An Australian university
      rehabilitation laboratory. PARTICIPANTS: Nine subjects presenting at 12 to 16
      months after unilateral ACL reconstruction using the semitendinosus/gracilis
      graft who were recruited from 2 orthopedic surgeons. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: JPS of the reconstructed and uninjured knees
      was examined by using the Peak Motus motion measurement system to record target
      joint angles and to calculate reproduced angles after limb movement into flexion
      and extension, performed in a weight-bearing position. RESULTS: There were no
      significant differences in JPS between reconstructed and uninjured knees (P=.68)
      or between the flexion and extension tasks (P=.47). CONCLUSION: There was no
      deficit in knee JPS 12 to 16 months after ACL reconstruction, as measured by a
      functional weight-bearing method. Further studies should examine the clinical
      utility of the method as a way to evaluate functional aspects of knee joint
      proprioception.

PMID- 12808541
TI  - Comparison between an indoor and an outdoor 6-minute walk test among individuals
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To investigate the feasibility of an outdoor 6-minute walk test
      (6MWT) as a measure of functional status among individuals with chronic
      obstructive pulmonary disease (COPD), and to examine the relationship between
      performance on an indoor and an outdoor 6MWT. DESIGN: An experimental, repeated
      measures crossover design. Subjects were studied on 2 separate days in the same
      week. Two 6MWTs-one indoors and the other outdoors-were performed on each study
      day, with a rest in between. The test order was randomly selected on the first
      day and reversed on the second day. Outdoor tests were performed on days of
      moderate weather conditions (mean temperature +/- standard deviation, 21 degrees
      +/-3 degrees C; mean wind speed, 15+/-7km/h; no precipitation) and on a flat
      surface (sidewalk). SETTING: Outpatient rehabilitation program in Ontario.
      PARTICIPANTS: Eighteen subjects with COPD (10 men, 8 women; age, 70+/-8y), 5
      using supplemental oxygen at rest (forced expiratory volume in 1s, 1.0+/-0.3L;
      42%+/-8% of predicted). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Distance walked in 6 minutes (in meters), duration of rest (in seconds), and
      change in rate of perceived dyspnea. RESULTS: There was no significant effect of
      setting (indoors vs outdoors) on distance walked (394+/-86m vs 398+/-84m, P=0.4),
      duration of rest (13+/-28s vs 9+/-20s, P=0.4), or change in rate of perceived
      dyspnea (2.3+/-1.7 vs 2.3+/-2.0, P=0.8). Testing day had no significant effect on
      walk test performance (all P>0.1). CONCLUSIONS: The results indicate that the
      6MWT performed outdoors within reasonable climatic parameters may be reflective
      of 6MWT performance indoors.

PMID- 12808542
TI  - The accuracy of needle placement in lower-limb muscles: a blinded study.
AB  - OBJECTIVE: To assess the accuracy of common anatomic guides for electromyographic
      needle placement in muscles. DESIGN: Blinded study. The dissector identified
      different needle placements by a random number attached to a wire in the
      insertion site. SETTING: A university anatomy laboratory. CADAVERS: Ten cadaver
      lower limbs. INTERVENTIONS: By using techniques published in texts by Gieringer
      and Delagi and Perotto, clinical electromyographers palpated and measured
      appropriate locations for needle placement. A thin wire was inserted through the
      needle into 36 different muscles in 10 cadavers, resulting in 263 targeted
      muscles. An anatomist blinded to intended location dissected and recorded muscles
      and other tissues that the wire pierced or passed near. MAIN OUTCOME MEASURES:
      Targeted muscle penetration, final resting place of the wire tip, and proximity
      to vital structures. RESULTS: Fifty-seven percent of insertions penetrated the
      intended muscle. The wire tip was in the intended muscle 45% of the time.
      Seventeen percent of insertions penetrated or passed within 5mm of an important
      structure, including nerve (9.1%), tendon (3.0%), named artery (2.7%), vein
      (2.7%), or joint (0.8%). Specific muscle accuracy was highly variable, from 0%
      for 12 tries in various deep hip muscles to 100% of 10 tries in the vastus
      medialis. CONCLUSION: The accuracy of blind needle placement varied according to
      muscle. With the blind insertion technique, more accurate and safe needle
      placement strategies can be developed.

PMID- 12808543
TI  - Reliability and validity of ankle proprioceptive measures.
AB  - OBJECTIVE: To determine the reliability and validity of ankle proprioceptive
      measures. DESIGN: Reliability was assessed between test occasions. Construct
      validity was addressed by the ability of measures to differentiate among groups.
      SETTING: Laboratory of an educational institution. PARTICIPANTS: Eight healthy
      adults were recruited into each of 3 groups: (1) young (20-39y), (2) middle-aged
      (40-59y), and (3) older adults (>or=60y). Four subjects from each group (n=12)
      participated in retesting. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Threshold for perception of passive movement, error in active reproduction of
      position, error in reproduction of velocity, and error in reproduction of torque.
      RESULTS: Intersession reliability was excellent (intraclass correlation
      coefficient [ICC] range, .79 - .95) for threshold for perception of movement,
      error in active reproduction, error in velocity reproduction, and error in
      dorsiflexion torque reproduction; intersession reliability was good for error in
      reproduction of plantarflexion torque (ICC=.72). Threshold for perception of
      movement differed between groups 1 and 3 and between groups 2 and 3 (P<.05).
      Error in reproduction of position was greater in group 2 than in group 1 (P<.05).
      CONCLUSION: Differences in proprioception between the older and the 2 younger
      groups were best detected by using threshold for perception of passive movement.

PMID- 12808544
TI  - State of the art in geriatric rehabilitation. Part I: review of frailty and
      comprehensive geriatric assessment.
AB  - OBJECTIVES: To increase recognition of geriatric rehabilitation and to provide
      recommendations for practice and future research. DATA SOURCES: A CINAHL and 2
      MEDLINE searches were conducted for 1980 to 2001. A fourth search used the
      Cochrane database. STUDY SELECTION: One author reviewed the reference for
      relevance and another for quality. A total of 336 articles were selected.
      Excluded articles were unrelated to geriatric rehabilitation or were anecdotal or
      descriptive reports. DATA EXTRACTION: The following major geriatric
      rehabilitation subtopics were identified: frailty, comprehensive geriatric
      assessment, admission screening, assessment tools, interdisciplinary teams, hip
      fracture, stroke, nutrition, dementia, and depression. Part I describes the first
      5 subtopics on concepts and processes in geriatric rehabilitation. Part II
      focuses on the latter 5 subtopics of common clinical problems in frail older
      persons. A level-of-evidence framework was used to review the literature. Level 1
      evidence was a randomized controlled trial (RCT) or a meta-analysis or systematic
      review of RCTs. Level 2 evidence included controlled trials without
      randomization, cohort, or case-control studies. Level 3 evidence involved
      consensus statements from experts or descriptive studies. DATA SYNTHESIS: Of the
      336 articles evaluated, 108 were level 1, 39 were level 2, and 189 were level 3.
      Recommendations were made for each subtopic. In cases in which several articles
      were written on the same topic and drew similar conclusions, the authors chose
      those articles with the strongest level of evidence, reducing the total number of
      references. CONCLUSIONS: Frail elderly patients should be screened for
      rehabilitation potential. Standardized tools are recommended to aid diagnosis,
      assessment, and outcome measurement. The team approach to geriatric
      rehabilitation should be interdisciplinary and use a comprehensive geriatric
      assessment. Medication reviews and self-medication programs may be beneficial.
      Future research should address cost effectiveness, consensus on outcome measures,
      which components of geriatric rehabilitation are most effective, screening, and
      what outcomes are sustainable.

PMID- 12808545
TI  - State of the art in geriatric rehabilitation. Part II: clinical challenges.
AB  - OBJECTIVES: To examine common clinical problems in geriatric rehabilitation and
      to make recommendations for current practice based on evidence from the
      literature. DATA SOURCES: A CINAHL database and 2 MEDLINE searches were conducted
      for 1980 to 2001. A fourth search was completed by using the Cochrane database.
      STUDY SELECTION: One author reviewed the references for relevance and another for
      quality. A total of 336 articles were considered relevant. Excluded articles were
      unrelated to geriatric rehabilitation or were anecdotal or descriptive reports on
      a small number of patients. DATA EXTRACTION: The following areas were the major
      geriatric rehabilitation subtopics identified in the search: frailty,
      comprehensive geriatric assessment, admission screening, assessment tools,
      interdisciplinary teams, hip fracture, stroke, nutrition, dementia, and
      depression. This article focuses on the latter 5 subtopics. The literature was
      reviewed by using a level-of-evidence framework. Level 1 evidence was a
      randomized controlled trial (RCT) or meta-analysis or systematic review of RCTs.
      Level 2 evidence included controlled trials without randomization, cohort, or
      case-control studies. Level 3 evidence involved consensus statements from
      experts, descriptive studies, or reports of expert committees. DATA SYNTHESIS: Of
      the 336 articles evaluated, 108 were level 1, 39 were level 2, and 189 were level
      3. Recommendations were made for each subtopic according to the level of evidence
      in the specific area. In cases in which several articles were written on a topic
      with similar conclusions, we selected the articles with the strongest level of
      evidence, thereby reducing the total number of references. CONCLUSIONS: Frail
      older patients with hip fracture should receive geriatric rehabilitation. They
      should also be screened for nutrition, cognition, and depression. Older persons
      should receive nutritional supplementation when malnourished. If severe dysphagia
      occurs in stroke patients, gastrostomy tube feeding is superior to nasogastric
      tube feeding.

PMID- 12808546
TI  - The diagnostic and therapeutic challenge of femoral head osteoid osteoma
      presenting as thigh pain: a case report.
AB  - Osteoid osteoma, an infrequent but important cause of musculoskeletal pain, is
      often difficult to diagnose. We present a case of a 31-year-old man who, for 2
      years, had left groin pain radiating to the thigh. Symptoms began 1 month after a
      motorcycle crash in which he sustained only shin abrasions. Initial spine and hip
      radiographs were negative. Treatment with naproxen provided significant relief,
      but the symptoms gradually worsened over 6 months. An electromyogram and lumbar
      magnetic resonance imaging (MRI) of the left lower leg were unremarkable. Hip MRI
      revealed edema without fracture. Prophylactic femoral pinning for impending
      stress fracture provided no relief. Rheumatologic evaluation revealed normal
      serologies and synovial fluid. Cyclobenzaprine and sulfasalazine were started and
      provided mild relief. At presentation to our institution, he was in significant
      discomfort, but could ride a bicycle for exercise and was completing a home
      exercise program. He had antalgic gait and globally restricted hip motion with
      end-range pain. A neurologic examination showed no abnormalities. Hip and pelvis
      computed tomography scan revealed increased sclerosis of the femoral head, with a
      central lucency suggestive of osteoid osteoma. This was confirmed by biopsy.
      Radiofrequency ablation provided significant symptom relief.

PMID- 12808547
TI  - Breathlessness associated with abdominal spastic contraction in a patient with C4
      tetraplegia: a case report.
AB  - A tetraplegic patient with C4 cervical cord injury reported breathlessness during
      episodes of spastic contraction of the abdominal muscles. To determine the
      mechanism, we performed electrophysiologic testing of the phrenic nerves. We
      measured abdominal pressure, esophageal pressure, and transdiaphragmatic pressure
      (Pdi) during a maximal inspiratory effort (Pdi max), a maximal sniff maneuver
      (sniff Pdi) during resting breathing, and during the episodes of breathlessness.
      Electrophysiologic testing of the phrenic nerves showed axonal neuropathy on the
      left. Sniff Pdi and Pdi max were 38cmH(2)O and 42cmH(2)O, respectively. Transient
      spastic contractions of abdominal muscles were associated with an increase in
      abdominal pressure greater than 30cmH(2)O, with a decrease in abdominal volume;
      this rise in abdominal pressure was transmitted to the esophageal pressure.
      Inspiration became effective only when esophageal pressure fell below the resting
      baseline value. Achieving this decrease required an increase in inspiratory
      effort, characterized by swings in esophageal pressure and Pdi of 30cmH(2)O and
      40cmH(2)O (approximately 100% of Pdi max), respectively. During these periods,
      minute ventilation was markedly reduced. This is the first report that spastic
      abdominal muscle contractions can impose a significant load on the diaphragm,
      uncovering moderate diaphragmatic weakness. This has important clinical
      implications; abolition of the spastic abdominal muscle contraction in this
      patient completely resolved her intermittent respiratory symptoms.

PMID- 12808548
TI  - Femoral, saphenous nerve palsy after tourniquet use: a case report.
AB  - Persistent motor and sensory abnormalities after surgery may affect the
      rehabilitation process. Patients with continued weakness may be perceived as
      lacking motivation by health care providers. However, there may be an underlying
      pathophysiologic abnormality preventing patients from progressing through their
      rehabilitation programs. We report a case of a 20-year-old man who underwent
      surgical repair of multiple knee structures with the use of a pneumatic
      tourniquet. Several weeks after surgery, electromyographic evaluation was done
      because he was having difficulty in his rehabilitation because of persistent
      weakness. An electromyography and nerve conduction study (NCS) revealed femoral
      and saphenous nerve palsies. Our report is the first on tourniquet-induced
      saphenous nerve injury as well as on abnormal femoral NCSs caused by tourniquet
      use. A review of the literature indicates that tourniquet-induced nerve palsies
      are not a rare event. Further evaluation should be considered if patients who are
      having persistent weakness or sensory findings after surgery have used a
      tourniquet.

PMID- 12808549
TI  - Use of a prone transfer technique in patients with severe hip-flexion
      restrictions: a report of 3 cases.
AB  - We report 3 cases in which the prone transfer technique improved the functional
      status of patients with postoperative restriction of hip flexion. All 3 patients,
      who had undergone a different type of surgery, were unable to get out of bed
      without a tilt table, and therefore could not be discharged home. The prone
      transfer technique enables patients to move from a lying to a standing position
      with or without the use of a flat board. All 3 patients were discharged home when
      they could perform this transfer without assistance. It required 10 to 18
      sessions of therapy training, which took place in 5 to 9 days. With advancements
      in surgical techniques, postoperative joint-motion restriction may be seen more
      frequently in community settings. Prone transfer may provide a low-cost, low
      technologic way to mobilize patients with hip-flexion restriction.

PMID- 12808551
TI  - A novel accelerometer tilt switch device for switch actuation in the patient with
      profound disability.
AB  - We describe the design and operation of a new switch that can be operated by
      patients with severely limited movement. The basis for the switch is an
      inexpensive single-chip accelerometer device. The switch responds to a relatively
      rapid rotation of the active components. We have ensured that the sensitivity of
      the switch device is adjustable over a wide range. The device automatically
      adjusts for changes in attitude of the device that result from a patient changing
      posture. We show that the device can operate in a wide range of attitudes. We
      describe 2 case studies in which the switch was successfully used as a head tilt
      switch.

PMID- 12808550
TI  - Robot-assisted arm trainer for the passive and active practice of bilateral
      forearm and wrist movements in hemiparetic subjects.
AB  - OBJECTIVE: To determine whether use of a robotic arm trainer for bilateral
      exercise in daily repetitive training for a 3-week period reduced spasticity and
      improved motor control in the arm of severely affected, chronic hemiparetic
      subjects. DESIGN: Before-after trial. SETTING: Community rehabilitation center in
      Germany. PARTICIPANTS: Consecutive sample of 12 chronic hemiparetic patients;
      minimum stroke interval 6 months; patients could maximally protract the affected
      shoulder, hold the extended arm, or slightly flex and extend the elbow.
      INTERVENTIONS: Additional daily therapy of 15 minutes with the arm trainer for 3
      weeks; the 1 degree of freedom trainer enabled the bilateral passive and active
      practice of a forearm pronation and supination and wrist dorsiflexion and
      volarflexion; impedance control guaranteed a smooth movement. MAIN OUTCOME
      MEASURES: Patients' impressions, the Modified Ashworth Scale (MAS) score (range,
      0-5) to assess spasticity, and the arm section of the Rivermead Motor Assessment
      (RMA) score (range, 0-15) to assess motor control were rated before therapy,
      after each 3-week interval, and at follow-up 3 months later. RESULTS: All
      patients had favorable impressions: the extremity felt more vivid, and 8 subjects
      noticed a reduction in spasticity, an ease of hand hygiene, and pain relief. The
      MAS score of the wrist and fingers joints decreased significantly (P<.0125) from
      a median of 3 (2-3) and 3 (3-4) to 2 (1-2) and 2.5 (2-3). The RMA score minimally
      increased in 5 cases without improvement in functional tasks. The median RMA
      score before therapy was 2.0 (1-2) and 2.0 (1-3.75) after therapy. There were no
      side effects. At follow-up, the effects had waned. CONCLUSIONS: The arm trainer
      made possible intensive bilateral elbow and wrist training of severely affected
      stroke patients. Future studies should address the treatment effect in subacute
      stroke patients and determine the optimum treatment intensity.

PMID- 12808552
TI  - An ankle-foot orthosis with inhibitor bar: effect on hemiplegic gait.
AB  - OBJECTIVE: To test whether an inhibitor bar attached to an ankle-foot orthosis
      (AFO) improves walking ability in hemiplegic stroke patients with tonic toe
      flexion reflex (TTFR). DESIGN: Before-after trial. SETTING: Rehabilitation
      hospital in Japan. PARTICIPANTS: Nine patients with TTFR were assigned to the
      TTFR group, and 8 patients without TTFR were assigned to the control group.
      INTERVENTION: Inhibitor bar attached to an AFO. MAIN OUTCOME MEASURE: Gait was
      analyzed by measuring the number of steps and the time required to walk 10m at a
      maximal walking speed. RESULTS: In the TTFR group, use of an inhibitor bar for 2
      weeks significantly increased the maximal walking speed, stride length, and
      cadence by 13.8% (P=.0045), 8.0% (P=.0398), and 6.1% (P=.0056), respectively.
      There were no significant changes in the control group. CONCLUSION: An inhibitor
      bar improved walking ability of hemiplegic patients with TTFR, and its use with
      an AFO is recommended.

PMID- 12808564
TI  - Cortical dysplasia in extratemporal lobe intractable epilepsy: a study of 52
      cases.
AB  - Cortical dysplasias or malformations due to abnormalities of cortical development
      are a well-recognized cause of intractable seizures. This study retrospectively
      examines the clinicopathologic features of 52 cases of extratemporal cortical
      dysplasia (from 135 total resections performed over a 16-year period). The study
      consists of 52 patients (27 males; 25 females) who underwent extratemporal
      resection for epilepsy at a mean age of 15.1 years (range, 3 months to 44.1
      years). Seizure duration before surgery ranged from 7 to 372 months (mean
      duration, 129 months). Patterns of cortical dysplasia observed included diffuse
      architectural disorganization (n=48), neuronal cytomegaly (n=32), increased
      number of molecular layer neurons (n=32), balloon cells (n=19), gray matter
      heterotopia (n=3), neuronal glial clustering (n=3), and pial glial neuronal
      tissue (n=2). Five patients had coexistent nodular hamartomas. Coexistent tumors
      were present in five patients; including three dysembryoplastic neuroepithelial
      tumors, one ganglioglioma, and one low-grade fibrillary astrocytoma. Two patients
      had tuberous sclerosis. Follow-up was available in 50 patients (mean follow-up,
      29 months). Thirty-eight patients (73%) had complete resolution or significant
      decrease in seizure frequency, 13 patients (25%) had increased seizures or no
      change in seizures, and one patient died in the postoperative period. In
      conclusion, (1). cortical dysplasia was identified in 38.5% of extratemporal
      resections for epilepsy; (2). the common cortical dysplasia patterns observed
      included diffuse cortical disorganization, neuronal cytomegaly, and increased
      molecular layer neurons; (3). 10% of extratemporal cortical dysplasia was
      associated with tumors; (4). improved seizure control was obtained in
      approximately three fourths of patients after resection; and (5). seizures
      associated with balloon cell dysplasia were less successfully managed with
      surgery.

PMID- 12808553
TI  - Myotonometer intra- and interrater reliabilities.
AB  - OBJECTIVES: To assess the intra- and interrater reliabilities of the
      Myotonometer, a hand-held, computerized, electronic device that quantifies muscle
      stiffness (tone/compliance). DESIGN: Reliability study. SETTING: Research
      laboratory. PARTICIPANTS: Thirty-five healthy, nondisabled adults (age range, 22
      42 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Two raters used the
      Myotonometer to evaluate subjects' lateral gastrocnemius and biceps brachii
      muscles. Muscles were measured in a relaxed state and during a voluntary
      isometric contraction. Coefficients were calculated for each muscle and each
      condition (relaxed, contracted). Results were analyzed by using Design II
      intraclass correlation coefficients. RESULTS: Reliability coefficients were
      highest when the instrument exerted moderate to strong forces against the muscle
      (range, 0.50-2.00 kg; intrarater reliability R range, .84 - .99; interrater
      reliability R range, .75 - .96). CONCLUSIONS: Myotonometer measurements had high
      to very high intra- and interrater reliabilities for measurements of the lateral
      gastrocnemius and biceps brachii muscles.

PMID- 12808565
TI  - Histologic analysis of chronic inflammatory patterns in the gallbladder:
      diagnostic criteria for reporting cholecystitis.
AB  - Cholecystectomy is one of the most common surgical procedures. Inflammatory
      disease is by far the most common pathology of the gallbladder. Terms for
      describing cholecystitis are numerous, thus there is no uniform terminology. One
      hundred cholecystectomies and 10 gallbladders from autopsies were reviewed and
      inflammatory changes were analyzed. Chronic cholecystitis was seen in 75% of
      cases with epithelial metaplasia and 73% with regenerative epithelium, the latter
      being associated with erosion but not with the presence of lithiasis. Muscular
      thickening and adipose deposits were mostly mild. Inflammation was mild in 28%,
      moderatein 57%, and severe in 15%. Activity was found in 29% of cases. Fibrosis
      was present in all cases: 26% mild, 62% moderate, and 12% severe. Autopsy cases
      did not show significant changes. A simple and reproducible scoring system of
      inflammation and fibrosis of the gallbladder is proposed. Three numbers refer to
      mild, moderate, or severe degrees of chronic inflammation and activity, with a
      final score that results from adding both values. The fibrosis is classified in
      three different stages. The final report uses both values to classify the chronic
      cholecystitis. A scoring system for chronic cholecystopathy to replace
      descriptive terms would give an exact transduction of the observed changes in an
      objective fashion that could not be misinterpreted by physicians or other
      pathologists.

PMID- 12808566
TI  - Sinonasal tract seromucous adenocarcinomas: a report of 12 cases.
AB  - Sinonasal seromucous adenocarcinomas may originate from the surface epithelium or
      from the submucosal glands. We reviewed the clinicopathologic material from 12
      patients with sinonasal tract seromucous adenocarcinomas at the University of
      Texas M. D. Anderson Cancer Center (Houston, TX). There were nine men and three
      women age 30 to 87 years (mean age, 56.3 years). The clinical presentation
      included nasal obstruction, nasal mass, and epistaxis. Eight tumors were located
      in the nasal cavity, three in the ethmoidal sinuses, and one involved the nasal
      cavity and ethmoid. Histologically, in nine cases the neoplastic glands were
      lined by a single cell type, arranged back to back without intervening stroma and
      often inducing desmoplastic reaction. The remaining three tumors also had a
      cribriform and papillary pattern. All patients were treated by surgical
      resection. Three patients had recurrences, which occurred at 36, 36, and 48
      months after initial therapy. Their treatment involved surgery and irradiation.
      Eleven patients are alive and free of disease at 36 to 108 months after
      diagnosis. One patient died 48 months after diagnosis of another cause. Sinonasal
      tract seromucous adenocarcinomas arise purely from submucosal seromucous glands.
      The diagnosis is facilitated by their anatomic location, the absence of tumor
      within the mucosal surface epithelium, and the striking similarity to terminal
      tubules of the seromucous glands.

PMID- 12808567
TI  - Pulmonary epithelioid hemangioendothelioma with prominent signet ring cell
      features mimicking metastatic adenocarcinoma.
AB  - We report the case of a 65-year-old woman who presented with persistent dry cough
      and was initially treated for pneumonia without much improvement. Computed
      tomography of the chest showed a 2.5 cm poorly marginated right infrahilar
      opacity and multiple ill-defined ground glass opacities scattered throughout the
      lungs. Computed tomography-guided fine needle aspiration of the right
      infrahilarmass showed malignant epithelioid cells, many of which were strikingly
      plasmacytoid with a vacuolated cytoplasm suggesting signet ring cells. A
      diagnosis of adenocarcinoma with signet ring cell features was made and, in view
      of the clinical history of multiple masses in the lung, metastatic adenocarcinoma
      from sites such as gastrointestinal or pancreaticobiliary tract was favored. The
      patient underwent exploratory thoracotomy during which she was found to have
      multiple, small pulmonary nodules, one of which was sampled for intraoperative
      examination. Frozen section of the nodule was interpreted as adenocarcinoma with
      signet ring cell features, probably metastatic in origin. Histopathologic
      examination of the pulmonary nodules demonstrated fairly well-delineated lesions
      with an acellular central zone of hyalinized matrix surrounded by a more cellular
      zone of moderately pleomorphic epithelioid cells, some of which had a
      peripherally displaced nucleus and vacuolated cytoplasm resembling signet ring
      cells. The epithelioid cells were positive for vascular markers CD31 and CD34
      and, therefore, a diagnosis of epithelioid hemangioendothelioma was confirmed.
      This case clearly indicates the importance of recognizing the cytomorphologic and
      histologic spectrum of this entity to avoid misdiagnosing it as either primary or
      metastatic adenocarcinoma.

PMID- 12808568
TI  - Polymorphous hemangioendothelioma of the neck.
AB  - Polymorphous hemangioendotheliomas are rare, low-grade borderline malignant
      vascular tumors of endothelial cell origin. To the best of our knowledge (MEDLINE
      1966-2002), there have been nine cases of polymorphous hemangioendothelioma
      reported in the English literature. Most of the initial patients reported were
      men, but we present the third case in a woman. Her previous radiation history to
      the neck makes this report unique. Polymorphous hemangioendothelioma is
      characterized by the variety of patterns of growth within and between tumors,
      making histologic recognition of the tumor difficult. Because management remains
      conservative via wide local excision, the misdiagnosis of this lesion as a
      malignancy has possible treatment implications. Alternatively, the high
      propensity for local recurrence underscores the necessity for accurate
      classification of the neoplasm and close clinical follow-up.

PMID- 12808569
TI  - Widely invasive solitary fibrous tumor of the sphenoid sinus, cavernous sinus,
      and pituitary fossa.
AB  - Solitary fibrous tumor is a spindle cell tumor first described in the pleura, but
      also found in multiple extrathoracic sites including the meninges, orbit, nasal
      and paranasal sinuses. No cases have been previously reported in the cavernous
      sinus or pituitary fossa. We present the case of a 54-year-old woman who
      presented with progressive amaurosis. On imaging studies, a widely infiltrative
      lesion involving the pituitary fossa, sphenoid sinus, cavernous sinus, carotid
      artery, medial temporal, ethmoid, and pterygoid bones, and extending into the
      nasopharynx was discovered; impression was a malignant tumor originating in the
      pituitary fossa. At surgery, the tumor was only partially resectable because of
      extensive bony invasion and encasement of the carotid artery, and was found to
      compress but not invade the pituitary gland. Histology showed a spindle cell
      proliferation with a dense, hyalinized collagenous stroma and dilated vascular
      spaces, some showing a staghorn-like appearance. Areas of cellular pleomorphism
      and increased cellularity were present, but few mitoses were identified.
      Immunohistochemistry showed strong positivity with CD34, factor XIIIa, CD99, and
      Bcl-2. There was scattered cyclin D1, mib-1, and p53 positivity. Muscle,
      epithelial, vascular, and melanocytic markers were negative. These results led to
      the diagnosis of solitary fibrous tumor. The size, extensive invasion, and bony
      destruction indicated a tumor with at least low malignant potential. The
      occurrence of solitary fibrous tumors in the pituitary fossa and sinuses of the
      head and neck is rare, but must be considered in the differential diagnosis of
      spindle cell lesions in these regions.

PMID- 12808570
TI  - Primary extramedullary plasmacytoma of the esophagus.
AB  - An uncommon manifestation of plasma cell neoplasia occurs outside the bone marrow
      and is designated "extramedullary plasmacytoma." These are usually encountered in
      mucosal sites of the head and neck region. The gastrointestinal tract may be
      secondarily involved in multiple myeloma or be the site of primary extramedullary
      plasmacytomas (PEMPs). The esophagus is the least common site of gastrointestinal
      PEMP. A 58-year-old man presented with dysphagia for solids over a period of 2
      months. Otherwise, he was well and systemic examination did not reveal anything
      of note. After a nondiagnostic biopsy, the patient was subjected to esophago
      gastrectomy. Gross examination of the esophagus revealed a large polypoid tumor.
      Histologically, it was composed of mature plasma cells, plasmablasts (some of
      which appeared anaplastic), and a minor admixture of lymphoid cells. Focally, the
      infiltrate permeated the squamous epithelium simulating lymphoepithelial lesions.
      The neoplastic cells were positive for epithelial membrane antigen, CD79a, IgG,
      and kappa, while the lymphoid cells were predominantly B cells. The patient did
      not have a monoclonal gammopathy. Skeletal x-rays and bone trephine examination
      were both normal. PEMP is biologically and prognostically different to other
      plasma cell neoplasms. Although rare, esophageal PEMP should be considered in the
      differential diagnosis of so-called undifferentiated malignant tumors of the
      esophagus.

PMID- 12808571
TI  - Microglandular adenocarcinoma of the uterus mimicking microglandular cervical
      hyperplasia.
AB  - We present a rare case of microglandular carcinoma of the uterus occurring in 76
      year-old woman. The tumor tissue in the curettage specimen showed strong
      similarity with microglandular hyperplasia of the cervix. Microglandular
      aggregates of glands with only mild nuclear atypia but without any structures of
      conventional endometrioid carcinoma were seen. Therefore, a microglandular
      hyperplasia of the cervix was seriously considered. The following features were
      helpful in the differential diagnosis: numerous neutrophils and "dirty" amount
      within glandular lumens; very scarce (but nevertheless present) mitoses; isolated
      single glands with more endometrioid than endocervical appearance; and strong
      expression of vimentin, which is unusual for microglandular hyperplasia of the
      cervix. In the resectate, a conventional well-differentiated endometrioid
      adenocarcinoma with microinvasion of the myometrium (under 1 mm of depth) was
      found. Microglandular differentiation has been, however, present in plaque-like
      proliferation replacing the endometrium and on the surface of conventional
      adenocarcinoma. Eleven months after the hysterectomy, the patient has no signs of
      recurrence or metastasis. Our case shows the difficulties in the diagnosis of
      this lesion and confirms a low aggressiveness that was observed in all 10 cases
      described to date.

PMID- 12808572
TI  - Infinitesimals, quantum mechanics, and exiguous carcinomas: how to possibly save
      a patient's larynx.
AB  - Occasionally, a patient will have a minimally invasive squamous cell carcinoma of
      the larynx that is such a meager carcinoma that, following biopsy, the larynx is
      surgically removed and the pathologic specimen contains no evidence of residual
      carcinoma or even significant dysplasia. Such gross overtreatment is a tragedy.
      How does this happen and what can a pathologist do to help preclude this event?

PMID- 12808573
TI  - Whatever happened to Dorothy Reed?
AB  - Born in 1874, Dorothy Reed entered the fourth medical school class at Johns
      Hopkins Medical School. After internship, she spent a year as University Fellow
      in Pathology, during which time she wrote and illustrated her well-known paper,
      "On the Pathological Changes in Hodgkin's Disease, With Especial Reference to Its
      Relationship to Tuberculosis." She left pathology at Hopkins after 1 year
      because, as a woman, she was told she could not be appointed to the faculty and
      because of an unhappy love affair. She took training in pediatrics, married a
      long-time friend, and moved to Madison, WI. Her first two children died
      tragically; subsequently, she gave birth to two fine boys. She developed a new
      career as a pioneer in maternal and child health. She established infant welfare
      clinics in Madison, wrote pamphlets for the United States Children's Bureau, and
      taught college students child development and sexual hygiene. For the first time,
      the identity of her lover and his role in establishing her fame is revealed.

PMID- 12808578
TI  - Remembering the contributions of Kenneth I. Howard.
AB  - This special issue of the Journal of Clinical Psychology recognizes the
      contributions of Kenneth I. Howard, one of the most influential and productive
      contemporary scholars in the domain of psychotherapy process and outcome. The
      articles address some of the major contributions by Dr. Howard and extend their
      implications to contemporary clinical practice and research.

PMID- 12808579
TI  - The dose-effect relationship in psychotherapy: a defining achievement for Dr.
      Kenneth Howard.
AB  - This article summarizes the Howard, Kopta, Krause, and Orlinsky (1986) study and
      notes its contributions to the field of psychotherapy. These contributions
      include (a) being the flagship study to estimate how psychotherapy is enough, (b)
      establishing number of sessions or dose as the common treatment unit of
      psychotherapy, (c) providing the first dosage standard for determining treatment
      groups, (d) inspiring the recent wave of effectiveness research, and (e)
      presenting the first methodology that assesses the efficiency of psychotherapy.

PMID- 12808580
TI  - Equivalence to normal?
AB  - The two articles discussed are integral ingredients of a greater whole Ken Howard
      envisioned. The first (Saunders, Howard, & Newman, 1988) refined our
      understanding of clinical significance, challenging researchers to clearly define
      the character and range of behaviors identified as normal or nonclinical for a
      specific population. The second (Rogers, Howard, & Vessey, 1993) focused on tests
      of equivalency between two experimental groups. Both were part of a general
      theme: A study's outcome requires a careful delineation of the norms and
      "normality" for that population as well as to whether the differences or
      equivalencies of the outcomes from these norms are important to the client, to
      the client's family, or to the community/society in which the client is to
      function. Ken's second authorship, typical on his many publications, honored his
      dedication to mentoring those who would improve upon what is currently
      understood.

PMID- 12808581
TI  - Efficacy, effectiveness, and expected treatment response in psychotherapy.
AB  - This article provides a summary of "The Evaluation of Psychotherapy: Efficacy,
      Effectiveness, and Patient Progress" (Howard, Moras, Brill, Martinovich, & Lutz,
      1996) and an introduction to the "patient profiling" method. First, the
      difference between the two main approaches to treatment research in
      psychotherapy, efficacy research and effectiveness research, are discussed. Next,
      the idea is introduced that both types of treatment-focused research strategies
      need to be supplemented by a patient-focused research strategy. The concept of
      patient profiling is presented as an application of such a patient-focused
      research strategy. The usefulness of patient profiling for monitoring and
      evaluating individual patients' progress in ongoing psychotherapy as well as for
      clinical decision making is described. An expression of the personal and
      professional impact of Ken Howard on the author is provided.

PMID- 12808582
TI  - What random assignment does and does not do.
AB  - Random assignment of patients to comparison groups stochastically tends, with
      increasing sample size or number of experiment replications, to minimize the
      confounding of treatment outcome differences by the effects of differences among
      these groups in unknown/unmeasured patient characteristics. To what degree such
      confounding is actually avoided we cannot know unless we have validly measured
      these patient variables, but completely avoiding it is quite unlikely. Even if
      this confounding were completely avoided, confounding by unmeasured Patient
      Variable x Treatment Variable interactions remains a possibility. And the causal
      power of the confounding variables is no less important for internal validity
      than the degree of confounding.

PMID- 12808583
TI  - The Pain Distress Inventory: development and initial psychometric properties.
AB  - A new 26-item self-report measure, the Pain Distress Inventory (PDI), was
      designed to assess affective distress symptoms related to physical pain. Phases 1
      to 3 were designed to construct the PDI using contemporary test development
      strategies. Studies 1 and 2 were conducted to define and confirm the four-factor
      oblique structure of the PDI: PDI-Depression, PDI-Anger, PDI-Pain Sensitivity,
      and PDI-Somatic Anxiety. The internal consistency reliability estimates were high
      for both the PDI total and scale scores. Study 3 examined relationships of the
      PDI with demographic variables and pain- and psychological-related responses.
      Scores on the PDI were useful in predicting scores on a pain-interference index
      and a pain-symptom index. Study 4 was designed to replicate previous findings of
      reliability and validity. The PDI total and scale scores were useful in
      differentiating between the responses of the clinic and nonclinic study
      participants. Limitations and potential uses of the PDI are discussed.

PMID- 12808584
TI  - A cautionary note on deviation scores for the WISC-III and WAIS-III.
AB  - This article highlights some dangers inherent in interpreting individual examinee
      strengths and weaknesses in WAIS-III and WISC-III profiles. In both manuals,
      there are tables providing point estimates for determining if a significant
      difference exists when comparing one subtest to the average of several subtests.
      However, these point estimates may lead to interpretation errors. A confidence
      interval approach that provides a solution to the interpretation problem is
      described and illustrated. These intervals show that differences between a single
      subtest score and the average subtest score that just reach statistical
      significance carry the potential of having no clinical significance.

PMID- 12808585
TI  - Couple alcohol treatment benefits patients' partners.
AB  - This study explored the effects of conjoint therapy on the partner of alcoholic
      patients. Seventy-five alcohol abusers were randomly assigned to one of two
      manualized alcoholism treatments. Effects on partners were evaluated on three
      outcome measures. Results indicated that partner alcohol use was initially high,
      but was improved by treatment. An assessment of cross-cutting dimensions of
      patient-treatment matching, found to be effective in predicting patient response,
      was then applied to the prediction of partner response. These dimensions were
      unsuccessful in predicting changes in partner response to treatment. Results are
      discussed in respect to possible differences in matching partners versus clients
      to treatment. The statistical representation of patient-treatment matching is
      discussed along with other topics for future Aptitude x Treatment interaction
      research.

PMID- 12808586
TI  - SEM and TEM analysis of water degradation of human dentinal collagen.
AB  - Recently several long-term studies have reported evidence of the hydrolytic
      degradation of collagen fibrils based on fractured surface observations after
      bond testing. Those studies suggested that one cause of the decline in the bond
      strength was the degradation of the collagen fibrils within the bonds. However,
      one concern has been raised that the dentinal collagen fibrils may be stable in
      water that does not contain oral bacteria or enzymes. Therefore, the present
      study aimed to clarify the micromorphological change in naked collagen fibrils
      after 500 days of water storage. To prepare exposed collagen fibrils, sectioned
      and polished human dentin surfaces were acid conditioned for 15 s with the use of
      two commercially available acid conditioners: All-Etch (10% phosphoric acid) and
      Uni-Etch (32% phosphoric acid) (Bisco, Inc.). Those specimens were stored in
      distilled water at 37 degrees C for 1 day (control) for 500 days. After the
      storage periods, the samples were examined with the use of SEM and TEM. Under SEM
      and TEM examination, micromorphological alterations (disarrangement of collagen
      web, widening the interfibrillar space, and the thinning diameter of collagen
      fibrils) were found in the specimens after 500 days in water.

PMID- 12808588
TI  - The effect of 30% hydrogen peroxide on the color of compomers.
AB  - The interaction between bleaching agents and recently introduced compomers has
      several issues that need to be explored, including morphology and mechanical
      properties. To investigate the effect of 30% hydrogen peroxide, a bleaching
      agent, on the color of compomers, three compomers (Compoglass F, Elan, and F2000)
      were polymerized, bleached up to 120 h, and then measured to determine the
      reflectance of the specimen during the bleaching process. Color differences were
      evaluated from the reflectance and color values that were represented by CIE
      L*a*b* values. Compomers stored in distilled water were used as a source of
      reference. Teeth were also used for comparison. Color differences for both the
      tested teeth and compomers and different periods of bleaching and soaking in
      distilled water showed statistically significant difference (p < 0.0001). Among
      the tested compomers, Compoglass F demonstrated the highest color difference. In
      addition, the color differences were maximal during the first 24 h. After 24 h,
      the color difference increased nearly linearly. Compomers stored in both a
      bleaching agent and distilled water did not exhibit much color difference between
      them. However, the color difference between teeth and compomers was considerable.

PMID- 12808587
TI  - Failure analysis of two Ti-alloy total hip arthroplasty femoral stems fractured
      in vivo.
AB  - Failure of total hip arthroplasty femoral stems is a serious clinical
      complication. Even modern metal alloys and designs sometimes suffer such
      incidents. The reported study aimed at the investigation of the reasons leading
      the in vivo fracture of two Ti6Al4V femoral stems. Stems were retrieved during
      revision surgery approximately 2 years postoperatively. Examination and analysis
      included XRF spectrometry for identification of chemical composition, macroscopic
      examination and topographical measurements, SEM study of fracture surfaces, study
      of alloy microstructure by optical microscopy, and finally measurement of
      mechanical properties by means of tensile testing conducted on alloy samples
      machined from the stems themselves. Macroscopic examination and measurements
      showed close topographical similarity between the two fractures. XRF
      spectrometry, tensile testing, and microstructure analysis identified the alloy
      as a typical Ti6Al4V surgical titanium alloy. During SEM analysis the fracture
      surfaces exhibited characteristic fatigue striations tidally running on the cross
      sections, which were considered as the weakest ones regarding toward geometry and
      stress concentration. Fracture in both stems occurred due to fatigue along these
      cross sections.

PMID- 12808589
TI  - Mechanical evaluation of a porous bone graft substitute based on poly(propylene
      glycol-co-fumaric acid).
AB  - A porous, resorbable polymer composite based on poly(propylene glycol-co-fumaric
      acid) (PPF) was mechanically evaluated in vitro for use as a bone graft
      substitute and fracture fixative. The test material created a dynamic system
      capable of initially providing mechanical integrity to bony voids and a
      degradative mechanism for ingrowth by native bone. The unsaturated polymer, PPF,
      was crosslinked in the presence of effervescent agents to yield a porous
      microstructure upon curing. An in vitro degradation study first assessed the
      temporal mechanical properties of the test material. This research was followed
      by an ex vivo study using a long-bone osteotomy model to characterize the
      mechanics of fixation. Results showed the initial compressive strength of the
      cross-linked PPF system was comparable to cancellous bone. The rate of strength
      loss was commensurate with the predicted mechanical recovery of healing bone with
      analogous results in a composite that comprised also 25% (by weight) autograft.
      Mechanical testing in the long-bone model demonstrated that PPF-based bone-graft
      substitute increased the flexural strength of K-wire stabilized osteotomies.
      These results suggest that this type of bone graft substitute may have clinical
      utility in the stabilization of complex tubular bone fractures.

PMID- 12808590
TI  - Effect of admixed high-density polyethylene (HDPE) spheres on contraction stress
      and properties of experimental composites.
AB  - Additives that provide stress relief may be incorporated into dental composites
      to reduce contraction stress (CS). This study attempted to test the hypothesis
      that conventional fillers could be replaced by high-density polyethylene (HDPE)
      spheres in hybrid and nanofill composites to reduce CS, but with minimal effect
      on mechanical properties. Nanofill and hybrid composites were made from a Bis
      GMA/TEGDMA resin having either all silica nanofiller or 75 wt.% strontium glass +
      5 wt.% silica and replacing some of the nanofiller or the glass with 0%, 5%
      (hybrid only), 10% or 20 wt.% HDPE. The surface of the HDPE was either left
      untreated or had a reactive gas surface treatment (RGST). Contraction stress (CS)
      was monitored for 10 min in a tensilometer (n = 5) after light curing for 60 s at
      390 mW/cm(2). Other specimens (n = 5) were light cured 40 s from two sides in a
      light-curing unit and aged 1 d in water before testing fracture toughness
      (K(Ic)), flexure strength (FS), and modulus (E). Results were analyzed by ANOVA
      with Tukey's multiple comparison test at p < 0.05. There was no difference
      between composites with RGST and untreated HDPE except for FS-10% HDPE hybrid
      (RGST higher). An increased level of HDPE reduced contraction stress for both
      types of composites. Flexure strength, modulus (hybrid only), and fracture
      toughness were also reduced as the concentration of HDPE increased. SEM showed
      evidence for HDPE debonding and plastic deformation during fracture of the hybrid
      composites. In conclusion, the addition of HDPE spheres reduces contraction
      stress in composites, either through stress relief or a reduction in elastic
      modulus.

PMID- 12808591
TI  - Degradation patterns of different adhesives and bonding procedures.
AB  - Various types of resin adhesives and procedures are available in the clinical
      field, so comprehensive understanding of degradation is required for each
      material and bonding procedure. The objective of this study was to investigate
      the bond durability for different adhesives and bonding procedures. Resin-dentin
      bonded beams were prepared with the use of two adhesives (One-Up Bond F/self
      etching primer system and One Bond/total-etch adhesive) and two experimental
      groups for the bonding procedure (wet and dry bonding of the total-etch
      adhesive). Those samples were soaked in water for 24 h(control), 6 and 12 months.
      After the water immersion, the bond strengths were measured by the microtensile
      bond test, and subsequently fractography was performed with the use of SEM.
      Statistically significant reduction of the bond strength (p < 0.05) was apparent
      after 12 months of water exposure in the range 22-48% of the control. The bonding
      resin was eluted from the hybrid layer of the self-etching and the total-etch
      adhesives for the wet bonding. Micromorphological alterations were found due to
      the hydrolysis of collagen fibrils with the total-etch adhesive for the dry
      bonding mode. These pathologic alterations were in accord with the bond strength.

PMID- 12808592
TI  - Effect of chemical etching and aging in boiling water on the corrosion resistance
      of Nitinol wires with black oxide resulting from manufacturing process.
AB  - The effect of chemical etching in a HF/HNO(3) acid solution and aging in boiling
      water on the corrosion resistance of Nitinol wires with black oxide has been
      evaluated with the use of potentiodynamic, modified potentiostatic ASTM F746, and
      scratch tests. Scanning-electron microscopy, elemental XPS, and Auger analysis
      were employed to characterize surface alterations induced by surface treatment
      and corrosion testing. The effect of aging in boiling water on the temperatures
      of martensitic transformations and shape recovery was evaluated by means of
      measuring the wire electroresistance. After corrosion tests, as-received wires
      revealed uniformly cracked surfaces reminiscent of the stress-corrosion-cracking
      phenomenon. These wires exhibited negative breakdown potentials in potentiostatic
      tests and variable breakdown potentials in potentiodynamic tests (- 100 mV to +
      400 mV versus SCE). Wires with treated surfaces did not reveal cracking or other
      traces of corrosion attacks in potentiodynamic tests up to + 900-1400-mV
      potentials and no pitting after stimulation at + 800 mV in potentiostatic tests.
      They exhibited corrosion behavior satisfactory for medical applications.
      Significant improvement of corrosion parameters was observed on the reverse scans
      in potentiodynamic tests after exposure of treated wires to potentials > 1000 mV.
      In scratch tests, the prepared surfaces repassivated only at low potentials,
      comparable to that of stainless steel. Tremendous improvement of the corrosion
      behavior of treated Nitinol wires is associated with the removal of defect
      surface material and the growth of stable TiO(2) oxide. The role of precipitates
      in the corrosion resistance of Nitinol-scratch repassivation capacity in
      particular-is emphasized in the discussion.

PMID- 12808593
TI  - Titanium-cell interaction: analysis of gene expression profiling.
AB  - Titanium and its alloys are used worldwide in surgery. Dental implants, screws
      and plates, prostheses, and surgical instruments are made with titanium-based
      metals. The favorable characteristics that make this material desirable for
      implantation are (a) mechanical proprieties and (b) biocompatibility. The latter
      has been demonstrated by in vivo studies with animal models and clinical trials
      over a 40-year period. However, the exact effect of titanium on cells is still
      not well characterized. Expression profiling by DNA microarray is a new molecular
      technology that allows the analysis of gene expression in a cell system. Several
      genes whose expression was significantly up- or downregulated in an osteoblast
      like cell line (MG-63) on titanium were identified with the use of DNA
      microarrays containing 19,200 genes. The differentially expressed genes are
      associated with a broad range of functional activities, including apoptosis,
      vesicular transport, and structural function. It was also possible to detect some
      genes whose function is unknown. The data reported are, to the author's
      knowledge, the first genetic portrait of titanium-cell interaction. They may help
      to provide a better understanding of the molecular mechanisms of titanium
      biocompatibility and serve as a model for studying the biocompatibility of other
      materials.

PMID- 12808594
TI  - Endotoxin contamination in wound dressings made of natural biomaterials.
AB  - Contamination by endotoxin of nine kinds of wound dressings made of natural
      biomaterials (calcium alginate, collagen, chitin, and poly-L-leucine) was
      examined with the use of water extracts. By applying the Limulus amoebocyte
      lysate (LAL) test, high concentrations of endotoxin were detected in extracts
      from three kinds of products made of calcium alginate. These extracts evoked
      fever in rabbits and induced the release of a proinflammatory (pyrogenic)
      cytokine, interleukin-6 (IL-6), from human monocytic cells (MM6-CA8). The effects
      disappeared when the extracts were treated with endotoxin-removing gel column
      chromatography or with an endotoxin antagonist, B464, confirming that the
      contaminating pyrogen was endotoxin. A noteworthy finding was that one of the
      endotoxin-containing extracts showed very weak IL-6-inducibility in human
      monocytic cells in contrast to its high pyrogenicity to rabbits. The discrepancy
      could be explained based on differences between humans and rabbits in sensitivity
      to the endotoxin, because the extract showed higher proinflammatory-cytokine (TNF
      alpha)-inducibility in rabbit whole-blood cells (WBCs) than human WBCs. The
      results suggest that the LAL test is a useful method of detecting endotoxin
      contamination in wound dressings and the MM6-CA8 assay is a good supplement to
      the LAL test for evaluating pyrogenicity in humans accurately.

PMID- 12808595
TI  - Glutaraldehyde-fixed kangaroo aortic wall tissue: histology, crosslink stability
      and calcification potential.
AB  - Stentless aortic heart valve substitutes, manufactured from biological tissues,
      are fixed with glutaraldehyde to cross-link collagen, reduce antigenicity, and
      sterilize the tissue. Despite improved cross linking, reduced antigenicity, and
      various anticalcification measures, the aortic wall tissue present in these
      prostheses tends to calcify. The aim of this study was to assess the morphology,
      collagen cross-link stability, and calcification potential of glutaraldehyde
      preserved kangaroo aortic wall tissue as opposed to porcine aortic wall tissue.
      Porcine and kangaroo aortic wall tissues were fixed in 0.625% buffered
      glutaraldehyde. Histology and cross-link stability were examined. Calcification
      potential was determined in the subcutaneous rat model. Kangaroo aortic wall
      tissue was significantly (p < 0.01) less calcified than porcine aortic wall
      tissue (26.67 +/- 6.53 versus 41.959 +/- 2.75 microg/mg tissue) at 8 weeks. In
      conclusion, the histological differences between kangaroo and porcine aortic wall
      tissue correlate well with the reduced calcification potential of kangaroo aortic
      wall tissue. The reduced calcification potential could result in improved long
      term durability of stentless kangaroo heart valves as bioprostheses.

PMID- 12808596
TI  - Frontal sinus and skull bone defect obliteration with three synthetic bioactive
      materials. A comparative study.
AB  - Three synthetic bioactive materials were studied in an experimental model to
      compare their usability in a frontal sinus and a skull bone defect obliteration.
      Bioactive glass number 9 (BAG(1)), bioactive glass number 13 (BAG(2)), and
      hydroxyapatite (HA) granules were investigated. BAG(1) and HA granules have been
      previously tested clinically. The clinical usefulness of BAG(2) granules has not
      been tested. Upper bony walls of 45 Elco rabbits' frontal sinuses were drilled
      open from four separate holes with the use of a standard method. The skull bone
      defects and the sinuses in frontal bone were filled with BAG(1) or BAG(2) on one
      side, and with HA on the other side. Two parallel posterior defects were covered
      with a pedicled periosteum flap, and two anterior defects with a free flap. The
      resorption of materials, new bone, and fibrous-tissue formation were observed
      with a histomorphometric method at 1, 3, and 6 months postoperatively. Scanning
      electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) were
      done at 6 months. In histomorphometry, the new bone formation increased with all
      the investigated materials throughout the study (p < 0.001), but the results
      showed higher new bone formation in the defects filled with BAG(1) than in
      corresponding BAG(2)- or HA- filled defects. New bone formation and resorption of
      materials were faster in defects covered by pedicled than by free periosteum
      flaps (p < 0.001). Intimate contact between the used materials and new bone was
      confirmed by SEM. FTIR analysis of bone produced by BAG(1) and BAG(2) was of the
      same type as natural frontal bone. BAG(2) can be manufactured in various shapes,
      and thus, could possibly be used in clinical conditions requiring a special
      anatomical implant shape. However, more research is needed regarding this
      property of BAG(2).

PMID- 12808597
TI  - Difference in polymerization color changes of dental resin composites by the
      measuring aperture size.
AB  - The objective of this study was to evaluate the influence of the
      illuminating/viewing aperture diameter of 11 mm/8 mm and 3 mm/3 mm and measuring
      geometry on the color and polymerization color changes of dental resin
      composites. Color of resin composites of 12 mm in diameter was measured on a
      reflection spectrophotometer with SCE and SCI geometry under D65 illumination.
      Before polymerization, difference in the three-color coordinates by the material
      was prominent in spite of the fact that the shade designation of all materials
      was the same. After polymerization, L* value decreased in hybrid composites but
      not in packable composites, and changes in a* value were small. When the same
      aperture size was used, polymerization color change with the SCE was generally
      higher than those with the SCI. Measured color was different by the aperture
      size, and the color difference was 16.82-27.05 before polymerization and 20.09
      28.51 after polymerization. General trends of polymerization color change were
      similar in both aperture sizes. Polymerization color changes with 3-mm aperture
      size were higher than those with 8-mm aperture size in hybrid resin composites in
      both geometries (p < 0.05); however, the color change was material dependent in
      the case of packable resin composites.

PMID- 12808598
TI  - Design and evaluation of novel blood incubation systems for in vitro
      hemocompatibility assessment of planar solid surfaces.
AB  - Success in the development of hemocompatible biomaterials depends on adequate
      equipment and procedures for standardized analysis of blood-materials
      interactions in vitro. In view of the limited standard of knowledge on that
      important aspect, two novel incubation systems were designed, built, and
      evaluated for the in vitro assessment of the hemocompatibility of planar solid
      surfaces: A screening setup was introduced for the comparison of up to 12
      different samples. A perfusion setup was developed to model the directed blood
      flow in the vascular system during incubation by a recirculation circuit,
      allowing the variation of the wall shear rate at the sample surface. The
      incubation procedures utilized freshly drawn, heparinized whole human blood.
      Hemocompatibility in terms of selected aspects of coagulation, thrombogenicity,
      and immune responses was quantified through plasma levels of characteristic
      molecules (immunoassays), cell counting, and analysis of adherent cells and
      fibrin formation (scanning electron microscopy), respectively. Prevention of
      blood-air contact and mechanical stress, constant temperature and blood pH during
      incubation, and the suitable choice of reference materials were found to be
      crucial for reliable testing. Considering those requirements, screening and
      perfusion system both provided sensitive discrimination between a given set of
      planar solid surfaces. In conclusion, the suggested methods for an in vitro
      hemocompatibility assessment permit versatile, sensitive, and efficient analysis
      of important blood-material interactions despite the unavoidable variability of
      blood characteristics in different experiments.

PMID- 12808599
TI  - Adsorption of parotid saliva proteins and adhesion of Streptococcus mutans ATCC
      21752 to dental fiber-reinforced composites.
AB  - The use of fiber-reinforced composites (FRC) in dentistry has increased during
      recent years. In marginal areas of crowns and removable partial dentures the
      fibers may become exposed and come into contact with oral tissues, saliva, and
      microbes. To date, few articles have been published on oral microbial adhesion to
      FRCs. The aim of this study was to compare different FRCs, their components, and
      conventional restorative materials with respect to S. mutans ATCC 21752 adhesion
      and adsorption of specific S. mutans binding proteins. Surface roughness of the
      materials was also determined. Four different FRCs, a restorative composite, and
      a high-leucite ceramic material were studied. Polyethylene FRC was found to be
      significantly rougher than all other materials. Aramid FRC also showed higher
      surface roughness in comparison with all materials but polyethylene FRC. Without
      a saliva pellicle, adhesion of S. mutans coincided with surface roughness and
      polyethylene and aramid FRC promoted S. mutans adhesion better than the other
      smoother materials. In the presence of salivary pellicle, ceramic and
      polyethylene FRC bound more bacteria than the other materials studied. Higher
      quantities of S. mutans binding proteins in the pellicles may in part account for
      the higher S. mutans adhesion to saliva-coated ceramic and polyethylene FRC.

PMID- 12808600
TI  - Microleakage and interfacial morphology of self-etching adhesives in class V
      resin composite restorations.
AB  - The purpose of the study was to evaluate the marginal leakage of three adhesive
      systems in Class V resin composite restorations. Two adhesive systems containing
      acidic primers: Clearfil SE Bond (CSEB) and Etch & Prime 3.0 (E&P), were compared
      with a conventional water-based primer: Scotchbond Multipurpose Plus (SBMP).
      Class V cavities were made at the cementum-enamel junction of extracted human
      molars, which were then divided between three groups. One of the adhesive systems
      was applied to each group following manufacturers' instructions. Composite
      restorations were placed, light cured for 40 s, and polished. Specimens were then
      immersed in a solution of 2% basic fuchsin dye for 24 h. Longitudinal sections
      were obtained and studied with a stereomicroscope for assessment of the
      microleakage according to the degree of dye penetration (scale of 0-3). Data were
      analyzed by Kruskal-Wallis one-way ANOVA, Mann-Whitney tests, and the Wilcoxon
      matched-pairs signed rank test. Two specimens for each group were analyzed by
      scanning-electron microscopy (SEM). Bonded interfaces of dentin were also
      examined by transmission-electron microscopy (TEM). On enamel, there were no
      significant differences between the three groups. On dentin, CSEB showed the
      lowest dye penetration values among the three adhesive systems. SEM and TEM
      studies showed hybrid layer and resin tag formations in all groups.

PMID- 12808601
TI  - Reduction of wear in total hip replacement prostheses by amorphous diamond
      coatings.
AB  - Wear-debris-induced periprosthetic bone loss and aseptic loosening is regarded as
      the main long-term problem of total hip replacements (THRs). In this study the
      amount of wear debris from articulating surfaces of THRs was reduced so as to be
      close to negligible by the use of high-quality amorphous diamond (AD) coatings
      deposited by pulsed plasma arc techniques. The wear rates determined in a
      commercial hip simulator for 15 million walking cycles (corresponding to about 15
      years of clinical use) in serum lubrication were even 1,000,000 times lower than
      the clinical values for conventional THRs (polyethylene-metal or metal-metal
      pairs). Elimination of wear debris and good biomechanical performance should
      provide a substantial improvement of the clinical longevity of the THRs.

PMID- 12808602
TI  - Bonded interface between a self-curing resin and dentin primed with a
      metalloprotein.
AB  - The purpose of this study was to investigate adhesive bonding between a self
      curing luting agent and dentin conditioned with a metalloprotein in terms of
      resin-dentin hybridization and interfacial polymerization. Of the six
      experimental primers containing bovine heart cytochrome c (BHCC), three contained
      2-hydroxyethylmethacrylate (HEMA) and the remaining three did not. The self
      curing luting agent used consisted of methyl methacrylate (MMA) and tri-n
      butylborane (TBB) with or without 4-methacryloyloxyethyl trimellitate anhydride
      (4-META). Bovine dentin surfaces were etched with 10wt% phosphoric acid, primed,
      and then bonded with stainless steel rods. After 24 h of water storage, the
      optimum bond strength was obtained with the 4-META/MMA-TBB luting agent and the
      aqueous primer contained 0.1 micromol/g BHCC and 35wt% HEMA. Microscopic
      observations showed continuity among the luting agent, the hybridized dentin, and
      the dentin substrate. A model experiment suggested that BHCC accelerates the
      polymerization of the 4-META/MMA/HEMA mixture from the hybridized dentin.

PMID- 12808603
TI  - Inverse relationship between tensile bond strength and dimensions of bonded area.
AB  - It is a known fact that there is a relationship between magnitude of bonded area
      and laboratory tensile test results. This relationship has been described for a
      range of areas between 1 and 10 mm(2), in extracted, nonperfused teeth. The aim
      of this study is to test this relationship in perfused teeth, with bonded areas
      ranging from 0.7 to 110.9 mm(2). Dentin of 92 sound third human molars was
      exposed and perfused, and three groups of bonded areas (BA) were delimited: small
      (0.69-1.89 mm(2)), medium (8.66-19.54 mm(2)), and large (58.91-110.86 mm(2)).
      Tensile bond strength (TBS) of three adhesive restorative systems was found. The
      best nonlinear curve estimation was searched (SPSS 9.0) between TBS and BA, for
      each and all materials. The best estimation was, for all materials, TBS = 4.17 +
      10.35/BA (p < 0.0001).

PMID- 12808604
TI  - Tantalum as a buffer layer in diamond-like carbon coated artificial hip joints.
AB  - The acid resistance of tantalum coated and uncoated human hip joint prostheses
      was studied with commercial CrCoMo acetabular cups. The samples were exposed to
      10% HCl solution and the quantities of dissolved Cr, Co, and Mo were measured
      with proton-induced X-ray emission (PIXE). The absolute quantities were obtained
      with the use of Cr and Se solution standards. Tantalum coatings (thicknesses 4-6
      microm) were prepared in vacuum with magnetron sputtering. Tantalum coating
      decreased the corrosion rate by a factor of 10(6). As a spinoff from recent wear
      tests on artificial hip joints it was shown that tantalum has excellent
      mechanical properties as an intermediate layer of diamond-like carbon (DLC)
      coatings. When tantalum was tested together with DLC on three metal-on-metal hip
      joint pairs in a hip simulator, no observable defects occurred during 15 million
      walking cycles with a periodic 50-300-kg load (Paul curve).

PMID- 12808605
TI  - Novel Guglielmi detachable coils (GDCs) for the treatment of brain aneurysms. In
      vitro study of hydroxyapatite coating on Pt plate as GDCs model.
AB  - With the use of an alternate soaking process a thin layer of hydroxyapatite (HAp)
      was formed on a platinum plate (Pt plate) which was used as a model for Guglielmi
      detachable coils (GDCs). The in vitro coagulant activity of the HAp-coated Pt
      plate was evaluated for the purpose of brain aneurysm treatment. In order to fix
      and to form the apatite layer homogeneously, beta-mercaptopropionic acid was
      immobilized onto the Pt surface prior to use. The HAp layer was formed on the
      beta-mercaptopropionic acid-fixed Pt plate surface, and quantitative control of
      apatite formation was achieved by controlling the number of alternate soaking
      process cycles. The HAp formed on the Pt plate surface was confirmed by X-ray
      diffraction and X-ray photoelectron spectroscopy studies. Blood interaction with
      the Pt plate was altered from nonthrombotic to highly thrombotic by forming a HAp
      layer on the surface. The alternate soaking process is an appropriate method to
      modify the GDCs. Complete treatment of brain aneurysms is expected with the use
      of HAp-coated GDCs, which would allow formation of a stable blood clot.

PMID- 12808606
TI  - Novel visible-light-induced photocurable tissue adhesive composed of multiply
      styrene-derivatized gelatin and poly(ethylene glycol) diacrylate.
AB  - A novel photocurable tissue adhesive glue, which is composed of styrene
      derivatized (styrenated) gelatin, poly(ethylene glycol) diacrylate (PEGDA), and
      carboxylated camphorquinone in phosphate-buffered saline (PBS), was prepared. The
      prototype formulation suitable for arterial repair was determined based on the
      gel yield, degree of swelling, tissue adhesive strength, and breaking (or burst)
      strength in vitro. The formulated photocurable tissue adhesive glue with an
      appropriate viscosity was converted to a water-swollen gel within 1 min of
      visible light irradiation. The tissue adhesive glue, which was coated on a rat
      abdominal aorta incised with a pair of scissors, was immediately converted to a
      swollen gel upon subsequent irradiation with visible light, and concomitantly
      hemostasis was completed. Histological examination showed that the produced gel
      was tightly adhered to the artery shortly after photoirradiation. The gel
      gradually degraded with time and was completely absorbed within 4 weeks after
      treatment. These results indicate that the photocurable glue developed here may
      serve as a tissue adhesive glue applicable to vascular surgery.

PMID- 12808607
TI  - Use of injectable calcium-phosphate cement for the fixation of titanium implants:
      an experimental study in goats.
AB  - This in vivo study evaluated the fixation of two types of titanium implants with
      the use of an injectable calcium-phosphate (CaP) cement. The cement was either
      used to create a cement mantle (Type A implant) or as an additive to press-fit
      placed titanium plasma sprayed implants (Type B implant). The implants were
      placed in trabecular bone of the medial femoral condyle of goats and left in
      place for 2 and 10 weeks. Mechanical evaluation of the implant fixation was done
      by torque testing. This showed that for the Type A implants the calcium-phosphate
      cement's performance was significantly inferior (P < 0.05) to that of
      polymethylmethacrylate cement fixation. For the two-week Type B implants a
      significant increase (P < 0.05) in failure load was found for calcium-phosphate
      cemented implants compared with just press-fitted Type B implants. Histological
      evaluation revealed that for Type A implants, failure during torque testing
      occurred at the implant-cement interface. In contrast, for Type B implants,
      failure occurred in the bone-implant interface for press-fit-placed devices and
      in the cement layer for CaP-cemented devices. Further, the CaP cement was found
      to be overgrown with new formed bone already after 2 weeks of implantation. The
      cement showed resorption due to regular bone remodeling. On the basis of these
      observations, it was concluded that the use of injectable CaP cement might
      facilitate earlier loading of press-fit inserted titanium implants. Nevertheless,
      the results have to be confirmed in dynamical mechanical as well as loaded in
      vivo studies.

PMID- 12808608
TI  - Fatigue testing and performance of acrylic bone-cement materials: state-of-the
      art review.
AB  - Over the past three decades or so, a very large volume of literature has been
      generated on the impact of an assortment of variables on the fatigue lifetimes of
      a large number of acrylic bone-cement formulations. In the present article, this
      literature is examined critically to reveal areas of agreement, areas of
      disagreement, as well as a welter of underexplored and unexplored topics. For
      example, there is unanimity of support for the notion that an increase in the
      molecular weight of the powder constituents or the fully cured cement leads to an
      increase in the cement's fatigue life, whereas there is disagreement as to
      whether vacuum mixing the cement constituents leads to an increase in the fatigue
      life of the fully cured cement (relative to the hand-mixed counterpart). Among
      the underexplored topics is systematic study of the effect of test frequency on
      the fatigue results, whereas determination of the optimal concentration of the
      antibiotic in an antibiotic-loaded cement is an example of the unexplored topics.
      It is pointed out that resolving the controversies, addressing the underexplored
      topics, and filling the lacunae will allow comprehensive evaluations of acrylic
      bone-cement materials to be made. This enhanced body of knowledge will prove
      invaluable in the continued use of acrylic bone cement as the anchoring agent in
      cemented arthroplasties.

PMID- 12808609
TI  - Tele-manipulator robots in surgery.

PMID- 12808610
TI  - Laparoscopic liver resection.

PMID- 12808611
TI  - Telemedicine in surgery.
AB  - BACKGROUND: Telemedicine is influencing surgical training, allows mentoring,
      proctoring and teleconferencing, and is increasingly being applied to carry out
      remote surgical procedures. A systematic review of the telemedicine systems
      available, along with a critical appraisal of their application, potential and
      limitations in the surgical field, has been undertaken. METHOD: Medline, Ovid and
      internet searches were carried out using the keywords 'telesurgery',
      'telepresence surgery' and 'telemedicine and surgery', along with hand searches
      of the two peer-reviewed telesurgery journals. RESULTS: Telementoring and
      teleconferencing have been used widely for surgical teaching and training. Two
      clinical telesurgery systems are currently available and have been a trial in
      patients undergoing a variety of operations including cholecystectomy, coronary
      artery bypass, prostatectomy and gastroplasty. Most studies have reported
      successful outcomes but with prolonged operating times. In 2002 the first long
      distance telesurgery procedure was successfully performed. CONCLUSION:
      Telemedicine has huge potential to alter surgical practice but improvements are
      required in telesurgical technology with respect to tactile feedback,
      instrumentation, telecommunication speed and availability. Issues of liability,
      legislation, cost and benefit require clarification. The future of telemedicine
      in surgery may lie in facilitating complex minimally invasive techniques.

PMID- 12808612
TI  - Sentinel lymph node mapping in colorectal cancer.
AB  - BACKGROUND: Ultrastaging, by serial sectioning combined with immunohistochemical
      techniques, improves detection of lymph node micrometastases. Sentinel lymph node
      mapping and retrieval provides a representative node(s) to facilitate
      ultrastaging. The impact on staging of carcinoma of the colon and rectum in all
      series emphasizes the importance of this technique in cancer management. Now the
      challenge is to determine the biological relevance and prognostic implications.
      METHODS: The electronic literature (1966 to present) on sentinel node mapping in
      carcinoma of the colon and rectum was reviewed. Further references were obtained
      by cross-referencing from key articles. RESULTS: Lymphatic mapping appears to be
      readily applicable to colorectal cancer and identifies those lymph nodes most
      likely to harbour metastases. Sentinel node mapping carries a false-negative rate
      of approximately 10 per cent in larger studies, but will also potentially upstage
      a proportion of patients from node negative to node positive following the
      detection of micrometastases. The prognostic implication of these micrometastases
      requires further evaluation. CONCLUSION: Further follow-up to assess the
      prognostic significance of micrometastases in colorectal cancer is required
      before the staging benefits of sentinel node mapping can have therapeutic
      implications.

PMID- 12808613
TI  - Systematic review of the safety and effectiveness of methods used to establish
      pneumoperitoneum in laparoscopic surgery.
AB  - BACKGROUND: A systematic review was conducted to determine which of the methods
      of obtaining peritoneal access and establishing pneumoperitoneum is the safest
      and most effective. METHODS: Studies that met the inclusion criteria were
      identified from six bibliographic databases up to May 2002, the internet, hand
      searches and reference lists. They were critically appraised using a validated
      checklist and data were extracted using standardized protocols. RESULTS: Meta
      analysis of prospective, non-randomized studies of open versus closed
      (needle/trocar) access indicated a trend during open access towards a reduced
      risk of major complications (pooled relative risk (RR(p)) 0.30, 95 per cent
      confidence interval (c.i.) 0.09 to 1.03). Open access was also associated with a
      trend towards a reduced risk of access-site herniation (RR(p) 0.21, 95 per cent
      c.i. 0.04 to 1.03) and, in non-obese patients, a 57 per cent reduced risk of
      minor complications (RR(p) 0.43, 95 per cent c.i. 0.20 to 0.92) and a trend for
      fewer conversions to laparotomy (RR(p) 0.21, 95 per cent c.i. 0.04 to 1.17). Data
      on major complications in studies of direct trocar versus needle/trocar access
      were inconclusive. Minor complications in randomized controlled trials were fewer
      with direct trocar access (RR(p) 0.19, 95 per cent c.i. 0.09 to 0.40),
      predominantly owing to a reduction in extraperitoneal insufflation. CONCLUSION:
      The evidence on the comparative safety and effectiveness of the different access
      methods was not definitive, but there were trends in the data that merit further
      exploration.

PMID- 12808614
TI  - Randomized clinical trial of the effect of microemulsion cyclosporin and
      tacrolimus on renal allograft fibrosis.
AB  - BACKGROUND: The aim of this study was to compare the effect of Neoral cyclosporin
      and tacrolimus-based therapy on the development of renal allograft fibrosis
      (chronic allograft nephropathy; CAN) in a prospective randomized trial. METHODS:
      A total of 102 patients undergoing renal transplantation were randomized to
      immunosuppression with either microemulsion cyclosporin (Neoral; 15 mg per kg per
      day adjusted to whole-blood trough concentrations of 200-300 ng/ml) or tacrolimus
      (0.2 mg per kg per day adjusted to whole-blood trough levels of 8-15 ng/ml) in
      conjunction with steroids, or at a lower dose (7 mg per kg per day and 0.1 mg per
      kg per day respectively) with the addition of azathioprine for non-heart-beating
      renal transplant recipients. Renal transplant interstitial fibrosis was
      quantified using computerized histomorphometric measurement of picrosirius red
      stained 1-year protocol renal transplant biopsies. Levels of interstitial
      fibrosis were compared in relation to observed efficacy and toxicity profiles of
      the two drugs. RESULTS: There was a significant increase in allograft
      interstitial fibrosis in the patients treated with Neoral compared with those
      given tacrolimus. There was no significant difference in the demographic
      characteristics between the patient groups or in the incidence of acute rejection
      (Neoral 36 per cent versus tacrolimus 35 per cent) or steroid-resistant rejection
      (both 10 per cent) between the two drugs. There was a higher incidence of insulin
      resistance in the tacrolimus group (post-transplant diabetes mellitus, glucose
      tolerance testing) but this was not statistically significant. Neoral was
      associated with a significant increase in total cholesterol (P = 0.030) and low
      density lipoprotein (P = 0.021) levels, which persisted throughout the study
      period. CONCLUSION: Despite equivalent efficacy and pretransplantation risk
      factors for CAN, Neoral was associated with increased allograft fibrosis and
      significantly higher serum low-density lipoprotein cholesterol levels compared
      with tacrolimus.

PMID- 12808615
TI  - Randomized clinical trial of the effect of interferon alpha on survival in
      patients with disseminated midgut carcinoid tumours.
AB  - BACKGROUND: Midgut carcinoid tumours often present with widespread disease making
      curative surgery impossible. Medical treatment therefore plays a major role in
      the treatment of these patients. METHODS: In this prospective randomized study,
      the effect of interferon (IFN) alpha on survival and risk of tumour progression
      was evaluated in 68 patients with midgut carcinoid tumours metastatic to the
      liver. All patients had undergone primary surgical treatment and hepatic arterial
      embolization of liver metastases before randomization. Patients were randomized
      to treatment with either octreotide alone (n = 35) or octreotide in combination
      with IFN-alpha (n = 33). RESULTS: Forty-one of the 68 patients died during a
      follow-up period of 33-120 months, equivalent to a 5-year survival rate of 46.5
      per cent. There was no significant difference in survival between patients
      treated with octreotide alone (5-year survival rate 36.6 per cent) and those
      given octreotide in combination with IFN-alpha (56.8 per cent). However, patients
      treated with IFN-alpha had a significantly reduced risk of tumour progression
      during follow-up (P = 0.008). CONCLUSION: Addition of IFN-alpha to octreotide may
      retard tumour growth in patients with midgut carcinoid tumours.

PMID- 12808616
TI  - Portal vein resection and reconstruction prior to hepatic dissection during right
      hepatectomy and caudate lobectomy for hepatobiliary cancer.
AB  - BACKGROUND: Hepatobiliary cancer invading the hilar bile duct often involves the
      portal bifurcation. Portal vein resection and reconstruction is usually performed
      after completion of the hepatectomy. This retrospective study assessed the safety
      and usefulness of portal vein reconstruction prior to hepatic dissection in right
      hepatectomy and caudate lobectomy plus biliary reconstruction, one of the common
      procedures for radical resection. METHODS: Clinical characteristics and
      perioperative results were compared in patients who underwent right hepatectomy
      and caudate lobectomy plus biliary reconstruction with (ten patients) and without
      (11 patients) portal reconstruction from September 1998 to March 2002. RESULTS:
      All ten portal vein reconstructions were completed successfully before hepatic
      dissection; the portal cross-clamp time ranged from 15 to 41 (median 22) min.
      Blood loss, blood transfusion during the operation, postoperative liver function,
      morbidity and length of hospital stay were similar in the two groups. No patient
      suffered postoperative hepatic failure or death. CONCLUSION: This study
      demonstrates that portal vein reconstruction does not increase the morbidity or
      mortality associated with right hepatectomy and caudate lobectomy with biliary
      reconstruction. This approach facilitates portal vein reconstruction for no-touch
      resection of hepatobiliary cancer invading the hilar bile duct.

PMID- 12808617
TI  - Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis leads to a systemic inflammatory response
      characterized by widespread leucocyte activation and, as a consequence, distant
      lung injury. In CC chemokines the first two cysteine residues are adjacent to
      each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC
      chemokine receptor antagonist, on pancreatic inflammation and lung injury in
      caerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was
      induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was
      administered either 30 min before or 1 h after starting caerulein injections, and
      pancreatic inflammation and lung injury were assessed. There were five groups of
      eight mice each including controls. RESULTS: Treatment with Met-RANTES had little
      effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung
      injury when given either before administration of caerulein (mean(s.e.m.) lung
      myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P
      = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63)
      lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio
      (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27)
      versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular
      permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). CONCLUSION:
      Treatment with Met-RANTES reduces lung damage associated with caerulein-induced
      pancreatitis in mice. Chemokine receptor antagonists may be of use for the
      treatment of the systemic complications of acute pancreatitis.

PMID- 12808618
TI  - Worldwide survey among polyposis registries of surgical management of severe
      duodenal adenomatosis in familial adenomatous polyposis.
AB  - BACKGROUND: The lifetime risk of developing duodenal cancer in familial
      adenomatous polyposis (FAP) is about 5 per cent. When and to what extent surgical
      intervention should be undertaken to prevent death from invasive carcinoma is
      controversial. The aim of this study was to determine the effectiveness of
      various surgical treatments for cancer and severe duodenal adenomatosis. METHODS:
      A questionnaire was mailed to the members of the Leeds Castle Polyposis Group to
      obtain data on patients with FAP, treated for duodenal cancer or severe duodenal
      adenomatosis after 1990. RESULTS: Sixty-nine patients were included. The
      indication for surgery was invasive cancer in 13 patients, of whom six died from
      metastatic disease. Fifty-six patients were initially treated for severe duodenal
      adenomatosis, five (9 per cent) of whom died from metastatic disease (P = 0.002).
      In surviving patients, adenomas recurred after ampullectomy (six of eight, at
      mean follow-up of 11 months), after duodenotomy with polypectomy (17 of 21, at
      mean 29 months) and after pancreatoduodenectomy (six of 25, at mean 47 months).
      None of six patients who underwent a pancreas-sparing duodenectomy had recurrence
      of adenoma (mean follow-up 11 months). CONCLUSION: Surgery for duodenal
      adenomatosis should take place before endoscopic biopsy reveals invasive cancer.
      Even after extensive surgical procedures, small bowel adenomas may occur,
      emphasizing the need for chemoprevention.

PMID- 12808619
TI  - Male gender adversely affects survival following surgery for colorectal cancer.
AB  - BACKGROUND: Previous studies have suggested that survival following surgery for
      colorectal cancer is better in women than men. However, the findings were
      inconsistent and few studies adjusted for case-mix. The aim of the present study
      was to establish whether there were gender differences in survival following
      surgery for colorectal cancer after adjusting for case-mix. METHODS: Some 3200
      patients who underwent resection for colorectal cancer between 1991 and 1994 in
      11 hospitals in Scotland were included in the study. Five-year survival rates,
      and the corresponding hazard ratios, adjusted for age, mode of presentation, site
      of tumour, the nature of surgery and Dukes stage, were calculated for men and
      women. RESULTS: Overall survival at 5 years was higher in women than men, in
      those with colonic tumours, those who underwent elective surgery and those who
      underwent apparently curative resection (all P < 0.001). Cancer-specific survival
      at 5 years was also higher in women (P = 0.008) and those who underwent elective
      surgery (P < 0.001). The adjusted hazard ratios, for women relative to men
      following curative resection, were 0.76 (95 per cent confidence interval (c.i.)
      0.68 to 0.85) (P < 0.001) for overall survival and 0.84 (95 per cent c.i. 0.73 to
      0.98) (P = 0.021) for cancer-specific survival. CONCLUSION: Following apparently
      curative resection for colorectal cancer and after adjusting for case-mix, there
      was an excess of both cancer-related and intercurrent deaths in men.

PMID- 12808620
TI  - Adverse association of oesophageal atresia and cleft lip and palate.

PMID- 12808621
TI  - Temporary closure of open abdominal wounds by the modified sandwich-vacuum pack
      technique.
AB  - BACKGROUND: A 5-year experience with the modified sandwich-vacuum pack technique,
      using an opened 3-litre urological irrigation bag and continuous high-pressure
      suction, for temporary abdominal wall closure is presented. METHODS: The records
      of all patients who underwent temporary abdominal wall closure using this method
      from January 1996 to December 2000 were examined. RESULTS: The modified sandwich
      vacuum pack was used 139 times in 55 patients. Forty patients sustained
      penetrating trauma while 15 patients sustained blunt trauma. The mean Injury
      Severity Score was 19 (range 9-34). Intra-abdominal sepsis (51 per cent) was the
      commonest indication, followed by visceral oedema (18 per cent), abdominal
      compartment syndrome (16 per cent), intra-abdominal packing (11 per cent) and
      abdominal wall defects (4 per cent). The overall mortality rate was 45 per cent.
      Three patients (5 per cent) developed enterocutaneous fistula. Of the 30
      survivors, 16 patients underwent primary fascial closure. CONCLUSION: The
      modified sandwich-vacuum pack technique of temporary abdominal wall closure is
      easy and rapid, cost effective and provides an effective means of containing
      abdominal wall contents.

PMID- 12808622
TI  - Adult small intestinal transplantation in England and Wales.
AB  - BACKGROUND: In 1996 two transplantation centres in the UK were commissioned by
      the National Specialist Commissioning Advisory Group for England and Wales to
      assess small intestinal transplantation in adults. The joint experience of the
      two centres is presented. METHODS: Patients with irreversible small intestinal
      failure and complications of parenteral nutrition, and those with abdominal
      disease requiring extensive visceral resection, were assessed as candidates and
      where appropriate listed for surgery. RESULTS: Thirty-six patients were assessed
      for small intestinal transplantation and, of these, 14 underwent surgery. Twelve
      patients survived the transplantation procedure. Of these, seven patients were
      alive at 1 year, five at 3 years and three at 5 years. Three patients remain
      alive. Patient and graft survival improved with experience; the 1-year survival
      rate improved in the last 4 years of this experience from 43 to 57 per cent, and
      the 3-year survival rate from 29 to 43 per cent. CONCLUSION: Small intestinal
      transplantation is associated with a high mortality rate but may benefit
      carefully selected patients in whom conservative management is likely to carry a
      greater mortality rate.

PMID- 12808623
TI  - Natural course of acquired undescended testis in boys.
AB  - BACKGROUND: Although orchidopexy is commonly performed for acquired undescended
      testis, therapy is still controversial. A prospective study on the natural course
      of acquired undescended testis in boys was initiated. METHODS: At present, the
      study includes 63 boys with 74 acquired undescended testes in whom treatment and
      follow-up has been completed. In 15 boys with 20 acquired undescended testes,
      orchidopexy was performed before the onset of puberty, mainly at the request of
      the parents. In the remaining 48 boys with 54 acquired undescended testes, the
      onset of puberty was awaited. Of these, four boys with four acquired undescended
      testes were lost to follow-up. RESULTS: In 42 of 50 boys the testis descended
      spontaneously at puberty with a testicular volume appropriate for age. In the
      remaining eight boys the testis failed to descend at puberty and orchidopexy was
      performed. CONCLUSION: The preliminary results of this study indicate that
      spontaneous descent at puberty commonly occurs in boys with acquired undescended
      testes, with testicular volume appropriate for age. It is suggested that surgical
      intervention before onset of puberty may not always be necessary in acquired
      undescended testis.

PMID- 12808624
TI  - Regional cerebral blood flow in patients with primary hyperparathyroidism before
      and after successful parathyroidectomy.
AB  - BACKGROUND: Single-photon emission computed tomography (SPECT) is used to study
      cerebral blood flow and cerebral metabolism in various neuropsychiatric
      disorders. Reduced regional cerebral blood flow has been demonstrated in patients
      with depression and chronic fatigue, symptoms that are common in primary
      hyperparathyroidism. The aim of this study was to reveal possible changes in
      regional cerebral blood flow in patients with primary hyperparathyroidism before
      and after operative treatment. METHODS: This was a prospective study of regional
      cerebral blood flow in 16 consecutive women of median age 72 (range 50-82) years
      using SPECT with (99m)Tc-labelled hexamethylpropylenamine-oxime. The measurements
      were performed before and 2, 4 and 12 months after parathyroidectomy. The
      Montgomery and Asberg depression rating scale (MADRS) depression score was used
      as a parallel clinical test. RESULTS: Reduced (pathological) regional cerebral
      blood flow was seen before operation in 14 patients, 13 with a solitary adenoma
      and one with double adenoma. After surgery, this improved to normal values in 13,
      but was further reduced in one. In two patients with preoperative normal regional
      cerebral blood flow, both of whom were asymptomatic and had diffuse hyperplasia,
      a slight reduction was demonstrated. Eight patients had a pathological
      preoperative MADRS score, which normalized in seven after surgical treatment.
      CONCLUSION: The finding of reduced regional cerebral blood flow in patients with
      primary hyperparathyroidism followed by significant improvement after operation
      might influence the case for surgical treatment.

PMID- 12808625
TI  - Image-directed parathyroidectomy under local anaesthesia in the elderly.
AB  - BACKGROUND: Surgical morbidity and mortality rates are increased in elderly
      patients. The aim of this study was to evaluate the outcome of targeted
      parathyroid operations in patients over the age of 70 years. METHODS: Forty
      patients aged over 70 years underwent targeted parathyroidectomy for primary
      hyperparathyroidism (HPT). Data were collected prospectively and reviewed
      retrospectively. RESULTS: : There were 33 women and seven men with a mean age of
      78 (range 70-92) years, all of whom had symptoms attributable to HPT. A solitary
      parathyroid adenoma was detected by ultrasonography and/or sestamibi scintigraphy
      before operation in all patients. Six patients had a history of neck surgery,
      including two with persistent or recurrent HPT. Thirty-three patients underwent
      neck exploration under local anaesthesia with intravenous sedation. Following
      parathyroidectomy, intraoperative parathyroid hormone levels normalized in 39 of
      40 patients and accurately predicted postoperative eucalcaemia. Intraoperative
      findings included 37 solitary adenomas, one double adenoma and two carcinomas.
      One patient with persistent HPT developed severe hypoparathyroidism following
      targeted parathyroid exploration with autotransplantation. Twenty-nine patients
      were discharged from hospital on the day of surgery. Nineteen of 21 patients for
      whom data were available reported an improvement in symptoms. CONCLUSION: A
      focused neck exploration provides a safe and effective alternative to bilateral
      neck exploration in elderly patients in whom a solitary parathyroid adenoma has
      been localized before operation. Targeted parathyroidectomy under local
      anaesthesia is recommended in most elderly patients with HPT.

PMID- 12808626
TI  - Limits and drawbacks of video-assisted parathyroidectomy.
AB  - BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) is a
      novel minimally invasive approach to primary hyperparathyroidism (PHPT). It is a
      gasless operation characterized by a single central incision and external
      retraction. This paper describes the drawbacks and limitations of this procedure
      based on a 5-year experience and 260 operations. METHODS: Of 364 patients with
      PHTP, 260 were selected for MIVAP. In most patients a unilateral minimally
      invasive exploration was performed. RESULTS: MIVAP was carried out successfully
      in 239 patients with a mean operating time of 40 (range 20-180) min. Conversion
      to cervicotomy was required in 21 patients (8.1 per cent). Complications included
      recurrent nerve palsy in two patients (0.8 per cent), haemorrhage that required
      reoperation 6 h after parathyroidectomy in one patient (0.4 per cent) and
      transient hypoparathyroidism in six patients (2.5 per cent). In five patients
      (2.1 per cent) persistent PHPT developed shortly after surgery. CONCLUSION: After
      5 years of experience, MIVAP appears to be feasible, safe and applicable to the
      majority of patients with PHPT.

PMID- 12808627
TI  - Role of endoscopic ultrasonography in screening and treatment of pancreatic
      endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type
      1.
AB  - BACKGROUND: Patients with multiple endocrine neoplasia (MEN) type 1 risk
      premature death from pancreatic endocrine tumours (PETs). Endoscopic
      ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A
      screening and therapeutic approach for asymptomatic patients is delineated in
      which EUS plays a pivotal role. METHODS: This was a retrospective study of 15
      patients with MEN-1 but with no symptoms of a PET. All patients underwent serum
      hormone measurement, including gastrin, and EUS. The findings were used to
      facilitate operative treatment. RESULTS: Six of 15 patients had a normal basal
      gastrin level and nine had a raised level. EUS demonstrated PETs in 14 patients
      and identified multiple lesions in 12. There was no predictive relationship
      between age or gastrin level and the number or size of PETs discovered. Thirteen
      patients have undergone enucleation or resection of PETs and two remain under
      observation. Nine of the 13 patients underwent transduodenal exploration to
      excise gastrinoma(s). One patient had lymph node metastases found at operation.
      There was no death. Self-limiting pancreatic fistula in five patients and biliary
      fistula in one. CONCLUSION: Early and aggressive screening using EUS identifies
      PETs in asymptomatic patients with MEN-1. Detection of tumours at an early stage,
      before the development of symptoms, lymph node metastases or liver metastases,
      may facilitate prompt surgical intervention and improve prognosis.

PMID- 12808628
TI  - Accuracy of fine-needle aspiration cytology in patients with radiation-induced
      thyroid neoplasms.
AB  - BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for selecting
      patients with thyroid nodules for thyroidectomy. Its value in patients who have
      been exposed to low-dose therapeutic radiation is questionable because these
      patients have an increased risk of multifocal benign and malignant tumours, and
      thyroid cancer is common in such patients. METHODS: Between 1960 and 1999, 171
      patients with one or more thyroid nodules who had a history of exposure to
      radiation underwent operation; 49 of these patients had preoperative FNAC. The
      cytology results in these 49 patients were compared with those of an age- and sex
      matched control group of patients with thyroid nodules who did not have a history
      of radiation exposure. RESULTS: Of those who had been exposed to radiation, six
      of 20 patients with 'benign' cytology by FNAC and six of 16 patients with
      'suspicious' cytology had thyroid cancer. All 13 specimens considered to be
      malignant on FNAC were indeed malignant. There was a higher rate of false
      negative cytological examinations among patients with a history of irradiation
      that in those without. CONCLUSION: FNAC of thyroid nodules in patients with a
      history of irradiation is not as accurate as that in non-irradiated patients,
      primarily because of coexisting occult thyroid cancers.

PMID- 12808629
TI  - Letter 1: Systemic inflammatory response predicts survival following curative
      resection of colorectal cancer (Br J Surg 2003; 90: 215-219).

PMID- 12808630
TI  - Letter 2: Systemic inflammatory response predicts survival following curative
      resection of colorectal cancer (Br J Surg 2003; 90: 215-219).

PMID- 12808631
TI  - Letter 3: Systemic inflammatory response predicts survival following curative
      resection of colorectal cancer (Br J Surg 2003; 90: 215-219).

PMID- 12808632
TI  - Letter 3: Moving from open to laparoscopic appendicectomy (Br J Surg 2003; 90:
      257-258).

PMID- 12808633
TI  - Letter 2: Moving from open to laparoscopic appendicectomy (Br J Surg 2003; 90:
      257-258).

PMID- 12808634
TI  - Letter 1: Moving from open to laparoscopic appendicectomy (Br J Surg 2003; 90:
      257-258).

PMID- 12808635
TI  - Female fecundity before and after operation for familial adenomatous polyposis
      (Br J Surg 2003; 90: 227-231).

PMID- 12808636
TI  - Low-cost laparoscopic cholecystectomy (Br J Surg 2002; 89: 1602-1607).

PMID- 12808637
TI  - Letter 1: Bone marrow micrometastasis in breast cancer (Br J Surg 2003; 90: 290
      301).

PMID- 12808638
TI  - Letter 2: Bone marrow micrometastasis in breast cancer (Br J Surg 2003; 90: 290
      301).

PMID- 12808639
TI  - Lesion progression with time and the effect of vascular occlusion following
      radiofrequency ablation of the liver (Br J Surg 2003; 90: 306-312).

PMID- 12808642
TI  - Studies on oogenesis and oviposition in the brown spider Loxosceles intermedia
      (Araneae: Sicariidae).
AB  - Loxosceles intermedia is a poisonous spider that has a wide distribution in
      southern Brazil, and constitutes a public health problem. In this study, the
      ovaries of mature females were examined by light and electron microscopy, and by
      histochemistry. Oocytes at all stages of development were observed in the same
      area of the mature ovarian wall, surrounded by a basement membrane and a proteic
      band. They were supported by a group of pedicular cells, which may function as
      follicular cells. No follicular cell was seen around the oocyte. Mature oocytes
      pass through the ovarian epithelial wall and are released into the ovarian lumen,
      covered by a vitelline membrane. The basement membrane and proteic band remain in
      the ovarian wall. On its way out, the oocyte is coated by proteins that will form
      the chorion. The presence of different coats throughout oogenesis, and at the
      time of egg release, is correlated with conditions that indicate fertilization
      occurs in the uterus lumen during oviposition.

PMID- 12808643
TI  - Morphological features in human cortical brain microvessels after head injury: a
      three-dimensional and immunocytochemical study.
AB  - We studied the morphology of cortical microvessels in the brains of 10 patients
      who had died after receiving a traumatic head injury (THI). Scanning electron
      microscopy (SEM) of vascular corrosion casts, confocal microscopy of histological
      sections after immunocytochemistry, and detection of apoptosis by terminal dUTP
      nick end labeling (TUNEL) were used. Microvascular casts showed an
      angioarchitectonic distribution that was defined as normal according to results
      obtained in a previous, nontraumatic series of subjects. However, when we
      compared them with previous works, the cast surface of some of the microvessels
      showed three types of morphological alterations: longitudinal folds, sunken
      surfaces with craters, and a significant flattening with reduction of lumen. The
      vessels that were primarily affected were the arterioles and capillaries of the
      middle and deep cortical vascular zones. Immunostaining with the monoclonal
      antibody MAS-336 against endothelial cells also showed the presence of
      longitudinal folds with a thinning of the vascular lumen, cytoplasmic round
      bodies, and a thickening of the endothelial cell membrane. The TUNEL technique
      revealed a positive staining of some endothelial cells. The structural
      alterations we observed indicate that microvessels undergo endothelial cell
      damage after THI. We suggest that this kind of lesion and the secondary
      functional injury to the blood-brain barrier (BBB) could play an important role
      in the development of the secondary lesions that these patients show in the
      subacute phase.

PMID- 12808644
TI  - Morphology and histology of chimpanzee primary visual striate cortex indicate
      that brain reorganization predated brain expansion in early hominid evolution.
AB  - Human brain evolution is characterized by an overall increase in brain size,
      cerebral reorganization, and cerebral lateralization. It is generally understood
      when brain enlargement occurred during human evolution. However, issues
      concerning cerebral reorganization and hemispheric lateralization are more
      difficult to determine from brain endocasts, and they are topics of considerable
      debate. One region of the cerebral cortex that may represent the earliest
      evidence for brain reorganization is the primary visual cortex (PVC), or area 17
      of Brodmann. In nonhuman primates, this region is larger in volume (demarcated
      anteriorly by the lunate sulcus), and extends further rostrally than it does in
      modern humans. In early hominid fossil (Australopithecus) endocasts, this region
      appears to occupy a smaller area compared to that in nonhuman primates. Some have
      argued that the brain first underwent size expansion prior to reorganization,
      while others maintain that reorganization predated brain expansion. To help
      resolve this question, we provide a description of two male, common chimpanzee
      (Pan troglodytes) brains, YN77-111 and YN92-115, which clearly display a more
      posterior lunate sulcal morphology than seen in other chimpanzees. These data
      show that neurogenetic variability exists in chimpanzees, and that significant
      differences in organization (e.g., a reduced PVC) can predate brain enlargement.
      While the human brain has experienced numerous expansion and reorganization
      events throughout evolution, the data from these two chimpanzees offer
      significant support for the hypothesis that the neurogenetic basis for brain
      reorganization was present in our early fossil ancestors (i.e., the
      australopithecines) prior to brain enlargement.

PMID- 12808645
TI  - Expression of cVg1 mRNA during chicken embryonic development.
AB  - Using degenerated PCR-primers to identify known and novel BMPs that are expressed
      in the developing chicken heart, we identified not only BMP2, -4, and -7 mRNA,
      but also the TGFbeta superfamily member cVg1. The expression pattern of cVg1 mRNA
      was determined during chicken development from HH4 to HH44. In early
      developmental stages, cVg1 mRNA is expressed in the primitive streak, paraxial
      mesoderm, developing somites, and developing neural tube. Subsequently, cVg1 mRNA
      is expressed in the developing central and peripheral nervous system, retina,
      auditory vesicle, notochord, lung alveoli, and olfactory mucosa. In the heart,
      cVg1 is initially expressed through the linear heart tube, but becomes restricted
      to the forming chamber myocardium, in an expression domain similar to that of
      atrial natriuretic factor (ANF) mRNA.

PMID- 12808646
TI  - Ontogenetic and regional morphologic variations in the turkey ulna diaphysis:
      implications for functional adaptation of cortical bone.
AB  - This study examines relationships between bone morphology and mechanically
      mediated strain/fluid-flow patterns in an avian species. Using mid-diaphyseal
      transverse sections of domestic turkey ulnae (from 11 subadults and 11 adults),
      we quantified developmental changes in predominant collagen fiber orientation
      (CFO), mineral content (%ash), and microstructure in cortical octants or
      quadrants (i.e., %ash). Geometric parameters were examined using whole mid
      diaphyseal cross-sections. The ulna undergoes habitual bending and torsion, and
      demonstrates nonuniform matrix fluid-flow patterns, and high circumferential
      strain gradients along the neutral axis (cranial-caudal) region at mid-diaphysis.
      The current results showed significant porosity differences: 1) greater osteocyte
      lacuna densities (N.Lac/Ar) (i.e., "non-vascular porosity") in the caudal and
      cranial cortices in both groups, 2) greater N.Lac/Ar in the pericortex vs.
      endocortex in mature bones, and 3) greater nonlacunar porosity (i.e., "vascular
      porosity") in the endocortex vs. pericortex in mature bones. Vascular and
      nonvascular porosities were not correlated. There were no secondary osteons in
      subadults. In adults, the highest secondary osteon population densities and
      lowest %ash occurred in the ventral-caudal, caudal, and cranial cortices, where
      shear strains, circumferential strain gradients, and fluid displacements are
      highest. Changes in thickness of the caudal cortex explained the largest
      proportion of the age-related increase in cranial-caudal breadth; the thickness
      of other cortices (dorsal, ventral, and cranial) exhibited smaller changes. Only
      subadult bones exhibited CFO patterns corresponding to habitual tension (ventral)
      and compression (dorsal). These CFO variations may be adaptations for
      differential mechanical requirements in "strain-mode-specific" loading. The more
      uniform oblique-to-transverse CFO patterns in adult bones may represent
      adaptations for shear strains produced by torsional loading, which is presumably
      more prevalent in adults. The micro- and ultrastructural heterogeneities may
      influence strain and fluid-flow dynamics, which are considered proximate signals
      in bone adaptation.

PMID- 12808647
TI  - Anatomical study of the pancreas in the house musk shrew (Suncus murinus), with
      special reference to the blood supply and innervation.
AB  - To examine the macroscopic structure, blood supply, and innervation of the
      pancreas in the house musk shrew (Suncus murinus), we performed gross anatomical
      dissection and whole-mount immunostaining of the autonomic nerve of Suncus
      pancreases based on neurofilament protein (NFP) immunoreactivity. The adult
      Suncus pancreas is clearly separated into right and left lobes that are not
      fused. The right lobe of the Suncus pancreas is located in the dorsum of the
      duodenum and to the right of the common bile duct independently. The right lobe
      is supplied by branches of the superior mesenteric artery, and is innervated by
      branches that originate from the superior mesenteric plexus and run along the
      arterial branches of the superior mesenteric artery. The left lobe occupies 9/10
      of the entire pancreas and is located to the left of the common bile duct. It is
      supplied mainly by branches of the splenic and common hepatic arteries, and is
      innervated by branches that originate from the celiac plexus and run along the
      splenic and common hepatic arteries. According to previous studies on the blood
      supply and innervation of the human pancreas, the right and left lobes of the
      Suncus pancreas correspond to the pancreatic parts derived from the ventral and
      dorsal pancreatic buds. The current results suggest that the Suncus pancreas is a
      suitable experimental model for studying the development of the human pancreas.

PMID- 12808648
TI  - Distribution of MHC II (+) cells in skin of the Atlantic bottlenose dolphin
      (Tursiops truncatus): an initial investigation of dolphin dendritic cells.
AB  - The skin is an important tissue of the immune system; however, little is known
      about immune cells in dolphin skin, and very few cetacean-specific immunoreagents
      are available for investigative purposes. Therefore, in this study
      immunohistochemistry techniques were used with species-specific and non-species
      specific antibodies to characterize immune cells, primarily focusing on
      Langerhans cells, in skin from the Atlantic bottlenose dolphin (Tursiops
      truncatus). An antibody to human major histocompatibility complex (MHC) class II
      molecules labeled cells with a dendritic-like morphology. The immunophenotype,
      morphology, and distribution of some of these cells are consistent with those of
      Langerhans cells. The cells were predominantly found in dermal papillae,
      primarily along the epidermal-dermal junction. Thus, the location of these cells
      was somewhat different from that in terrestrial mammals. Other MHC II (+) cells
      of varying morphology were observed deeper in the dermis, with a perivascular
      concentration, and had characteristics of macrophages and dermal dendritic cells.
      There was no immunostaining with cetacean-specific CD2 or CD21. In diseased skin,
      a subjective increase of MHC II (+) cells, most notably in the superficial skin
      layers, was associated with an ulcerative dermatitis. A few CD2 (+) cells were
      also present. Differences between dolphins and terrestrial mammals in terms of
      morphology, mechanisms of response to insult and repair, and environmental
      challenges may explain the modified distribution of MHC II (+) cells in dolphin
      skin. An elucidation of the immune cells in cetacean skin will contribute to our
      understanding of the evolution of functional adaptations to various environments,
      facilitate diagnosis of skin diseases, and define the potential for intradermal
      administration of vaccines and other immunotherapeutics.

PMID- 12808649
TI  - Anatomy and motor pathways of the electric organ of skates.
AB  - The electric organ of skates is a paired structure within the tail consisting of
      two longitudinal columns of electrocytes contained within the lateral musculature
      on each side of the vertebral column. The electrocytes develop from hypaxial
      skeletal muscle fibers, and, depending upon the species, are generally classified
      as either cup-shaped or disc-shaped. The disc-shaped electrocytes are considered
      to be the more derived type. Regardless of the morphology of the electrocyte, the
      electric organ discharge of all skates is characterized as a weak asynchronous
      and long-lasting signal. Although recent behavioral investigations have revealed
      a communicative function for the electric organ, details as to which specific
      behaviors utilize this motor system remain uncertain. The electric organ is
      innervated by segmental motor nerves that branch from the ventral root of caudal
      spinal nerves at all levels of the electric organ. The cells of origin of the
      electromotor nerves, or electromotoneurons (EMNs), are large multipolar neurons
      with extensive dendrites located within the ventral gray matter of the spinal
      cord. The EMNs are uniformly distributed among the somatic motoneurons at levels
      corresponding to the rostrocaudal extent of the electric organ, and therefore do
      not form a discrete nucleus. The medullary command nucleus is comprised of
      neurons located within the nucleus raphe magnus, and forms a descending spinal
      pathway to the EMNs.

PMID- 12808650
TI  - Fine structure of soft and hard tissues involved in eye migration in
      metamorphosing Japanese flounder (Paralichthys olivaceus).
AB  - The body of a Japanese flounder (Paralichthys olivaceus) changes from a
      symmetrical to an asymmetrical form during metamorphosis. To obtain detailed
      information on the mechanisms of the migration of the right eye to the left side,
      soft and hard tissues in the head of larval flounders were examined using
      transmission electron microscopy (TEM). Retrorbital vesicles (Rvs) are pairs of
      sac-like structures under the eyes. It has been suggested that the asymmetrical
      development of Rvs, with the right (blind) one being bigger than the left, is the
      driving force behind eye migration. The present study revealed that the
      ultrastructure of the Rv sheath is quite similar to that of a lymphatic
      capillary. Thus, it is possible that the Rv is a part of the lymph system, and is
      probably related to the secondary vascular system in teleosts. If we assume that
      the Rv sheath has a high permeability to liquid, similar to lymphatic
      capillaries, it is not plausible that the active expansion of the Rv pushes the
      eyeball. On the other hand, the pseudomesial bar (Pb) is a bone that is unique to
      flounders and is present only on the right (blind) side. At the beginning of eye
      migration, an aggregation of fibroblast-like cells is observed in the dermis
      under the right eye, where the Pb will subsequently be formed. These cells have a
      well-developed rough endoplasmic reticulum (rER) and mitochondria, and are
      probably responsible for formation of the thick layers of collagen fibrils around
      them. Since it is unlikely that the active expansion of the Rv causes eye
      migration, the role played by the Pb and its rudiment becomes more significant in
      right eye migration in the Japanese flounder becomes more significant.

PMID- 12808653
TI  - Anterior skull base surgery for malignant tumors: a multivariate analysis of 27
      years of experience.
AB  - INTRODUCTION: Few studies have examined prognostic factors that have an impact on
      outcomes in anterior skull base surgery by multivariate analysis. METHODS: We
      retrospectively examined our institution's skull base experience from 1973-2000.
      RESULTS: During this time, 166 patients underwent an anterior skull base
      resection for malignancy (median age, 53 years; range, 6-92 years). The 5-year
      relapse-free and disease-specific survival was 41% and 57% (median follow-up, 53
      months). Multivariate analysis found that dural invasion, primary histologic
      diagnosis, and margin status had a significant impact on relapse-free and disease
      specific survival. CONCLUSIONS: These data indicate that patients with anterior
      skull base malignancies are treated successfully with skull base surgery.
      Patients demonstrating adverse prognostic variables such as dural invasion,
      adverse histologic findings, and/or positive margins should be considered for the
      addition of adjuvant therapy or innovative therapies as they become available in
      the future.

PMID- 12808654
TI  - The value of frozen section in intraoperative surgical management of thyroid
      follicular carcinoma.
AB  - BACKGROUND: Preoperative and intraoperative diagnosis of follicular carcinoma
      (FC), resulting in one-stage surgical treatment of follicular thyroid tumors, is
      an important issue in thyroid surgery. METHODS: In the 10-year period there were
      4158 operations performed on thyroid gland. There were 1559 patients with
      follicular tumors, 70 (4.4%) of them having FC. We analyzed the groups of
      patients with FC determined on frozen section (FS) and permanent section (PS)
      according to duration of clinical symptoms, ultrasound (US) examination, tumor
      size, patient gender and age, intensity of invasion, localization, and multiple
      or solitary occurrence of tumor. RESULTS: FC was diagnosed in 39 (55.7%) patients
      on frozen section (FS). Among the encapsulated (minimal invasion) carcinomas, the
      FS was accurate in 19 of 33 (57.6%) FC and in 5 of 15 (27.8%) Hurthle cell
      carcinomas (HCC); among extensively invasive carcinoma in 11 of 14 (78.6%) FC and
      in 4 of 5 (80.0%) HCC. FC was significantly more common in men (p <.001) and in
      the right lobe (p <.05). We did not find statistically significant differences
      concerning duration of symptoms, US examination, tumor size, patient age, and
      multiple or solitary occurrence of the tumor between the patients with FC
      diagnosed on FS and the patients with FC diagnosed on PS. CONCLUSIONS: The
      intraoperative diagnosis of FC is difficult. Although the percentage of false
      negative results was relatively high (44.3%), there were no false-positive
      results. This means that the second operation was avoided in 55.7% of the
      patients, and no unnecessary thyroidectomies were performed. FS biopsy is an
      important method in surgery of follicular tumors. Improved technical support and
      the ability to analyze a greater number of slides will increase the accuracy of
      the method.

PMID- 12808655
TI  - Radiation therapy for esthesioneuroblastoma: rationale for elective neck
      irradiation.
AB  - PURPOSE: Esthesioneuroblastoma is an uncommon malignancy of neural crest origin
      arising in the upper nasal cavity. We describe the University of Florida
      experience using radiation therapy (RT) in the treatment of this neoplasm,
      particularly the use of elective nodal irradiation. MATERIALS AND METHODS:
      Between May 1972 and August 1998, 22 patients received RT for
      esthesioneuroblastoma. Two additional patients were treated with palliative
      intent and were excluded from analysis. Equal numbers of male and female patients
      were treated, with a median age of 54 years (range, 3-82). The modified Kadish
      stage was A in 1 patient, B in 4 patients, C in 15 patients, and D in 2 patients.
      Treatment modalities included primary RT in 6 patients, preoperative RT in 1
      patient, postoperative RT after craniofacial resection in 12 patients, and
      salvage RT in 3 patients treated for recurrence after surgery. Elective neck RT
      was performed in 11 of 20 patients; 2 patients had cervical metastases at
      presentation for RT. RESULTS: Rates of local control, cause-specific survival,
      and absolute survival at 5 years were 59%, 54%, and 48%, respectively. The cause
      specific survival rate at 5 years was lower after primary RT (17%) than after
      craniofacial resection and postoperative RT (56%). Cervical metastases occurred
      in 6 of 22 patients (27%). No neck recurrences occurred in 11 patients treated
      with elective neck RT compared with 4 neck recurrences in 9 patients (44%) not
      receiving elective neck RT (p =.02). CONCLUSIONS: Combined modality therapy is
      preferred over RT alone in advanced-stage esthesioneuroblastoma. Our data and
      review of the current literature suggest a higher cervical failure rate than
      previously recognized. Elective neck RT seems to correlate with improved nodal
      control and should be considered in the treatment of esthesioneuroblastoma.

PMID- 12808656
TI  - Parameters that predict local control after definitive radiotherapy for squamous
      cell carcinoma of the head and neck.
AB  - PURPOSE: To analyze parameters that may influence the likelihood of local control
      after definitive radiotherapy for head and neck cancer. METHODS: Between April
      1980 and January 2000, 404 patients were treated with definitive RT alone (358
      patients) or combined with adjuvant chemotherapy (46 patients) at our institution
      and were followed up for 0.25 to 20.25 years (median, 3.5 years.) All living
      patients were followed up for at least 2 years. All patients had the primary
      tumor volume calculated on pretreatment CT. End points were local control after
      RT and local control after RT without a severe late complication. Parameters
      evaluated in multivariate analyses of these end points included primary site, T
      stage, primary tumor volume, N stage, histologic differentiation, fractionation
      schedule, adjuvant chemotherapy, and gender. RESULTS: The rates of local control
      and local control without a severe late complication after RT were significantly
      influenced by primary tumor volume for patients with cancer of the supraglottic
      larynx and true vocal cord. In contrast, the rates of local control and local
      control without severe complications for patients with tumors of the oropharynx
      and hypopharynx were less influenced by tumor volume. Multivariate analysis of
      the overall population revealed that the only parameter that was significantly
      related to the probability of local control after RT was T stage. Multivariate
      analyses stratified by primary site revealed that tumor volume significantly
      influenced local control for patients with cancers of the supraglottis (p =.0220)
      and glottis (p =.0042) but not for those with lesions of the tonsillar
      fossa/posterior tonsillar pillar (p =.0892), base of tongue (p =.9493), anterior
      tonsillar pillar/soft palate (p =.5909), and hypopharynx (p =.2282). CONCLUSIONS:
      The most important parameter that has an impact on local control after RT is T
      stage. Primary tumor volume also significantly influences the probability of
      local control in cancers of the supraglottis and glottis.

PMID- 12808657
TI  - Parotid gland surgery: 4-year review of 118 cases in an Asian population.
AB  - BACKGROUND: To determine the presentation and management of parotid lesions
      requiring excision in a largely Chinese Asian population. METHODS: Retrospective
      study of 118 consecutive parotidectomies. RESULTS: Thirty-seven percent were
      Warthin's tumor (WT), 33% pleomorphic adenoma (PA), 21% other benign disease
      (OBD), and 9% malignant tumor (MT). Mean age was significantly different between
      benign (51 years) and malignant (40 years) lesions. MT decreased above 50 years,
      but increased five times with pain and two times with a noninferior pole lesion.
      Sensitivity of fine-needle aspiration (FNA) for differentiating benign from MT =
      78%, for WT =5 8%, for PA =82%, for OBD = 28%, and for MT = 38%. CT scans did not
      alter WT management. Facial nerve (FN) paresis was not associated with histology,
      tumor size, site, or parotidectomy type. CONCLUSIONS: This is the first report
      documenting that most benign parotid tumors are WT and not PA. MT risk is greater
      in those less than 50 with pain and a noninferior pole lesion. Cystic lesions
      such as WT require great care in the evaluation of FNA findings.

PMID- 12808658
TI  - Microvascular free tissue transfer in elderly patients: the Toronto experience.
AB  - BACKGROUND: Microvascular free tissue transfer has become an accepted and
      versatile method of reconstruction in the head and neck region, offering a one
      stage procedure and thus reducing the number and length of hospital stays. Many
      of the patients requiring head and neck free flaps are elderly, with concomitant
      medical problems, including respiratory and cardiovascular compromise, and are
      therefore potentially at higher risk of adverse outcomes. In addition, they
      frequently have a history of heavy alcohol and cigarette consumption, which can
      compound the risks. METHODS: We analyzed a series of 288 intraoral free flap
      reconstructions and arbitrarily divided them into four groups depending on age:
      <50, 51-60, 61-70, >70. These reconstructions were all performed for malignant
      lesions. Preoperative medical problems, including ischemic heart disease,
      hypertension, chronic obstructive pulmonary disease, peripheral vascular disease,
      and diabetes, were assessed and compared among the different age groups.
      CONCLUSIONS: Our results suggest that free flap surgery is a safe technique in
      elderly patients with comparable surgical complications to a younger patient
      population. As a result of concomitant medical problems, however, postoperative
      medical complications are more frequent in the older age groups, with a resultant
      increase in length of hospital stay.

PMID- 12808659
TI  - Biodegradable polymer-mediated intratumoral delivery of cisplatin for treatment
      of human head and neck squamous cell carcinoma in a chimeric mouse model.
AB  - BACKGROUND: The effectiveness of chemotherapeutic agents is proportional to the
      dose of the agents at their targets; however, the dose is limited by systemic
      toxicity. Attempts have been made to improve therapeutic effectiveness by
      increasing maximum tolerated dose (MTD) of chemotherapeutic agents using various
      local and regional drug delivery systems. Herein we report the use of an
      injectable biodegradable polymer to deliver cisplatin for intratumoral treatment
      of human head and neck squamous cell carcinoma (HNSCC) in a chimeric mouse model.
      The objectives of this research project were (1) to determine the release
      kinetics of cisplatin from the polymer delivery system, (2) to identify the MTD
      of polymer-delivered cisplatin, and (3) to evaluate its therapeutic efficacy.
      METHODS: To determine the in vivo release kinetics, cisplatin-loaded polymer was
      injected subcutaneously into rats. Implants were removed and analyzed for
      remaining cisplatin by a high-performance liquid chromatography technique. Sera
      from these rats were assayed for platinum by atomic absorption spectrophotometry.
      For MTD determination, SCID mice were engrafted subcutaneously with fresh biopsy
      specimens of HNSCC. Various doses of free or polymer-loaded cisplatin were
      injected intratumorally. MTD was estimated based on the threshold at which all
      mice survived. The antitumor efficacy of free and polymer-loaded cisplatin at
      their respective MTD was assayed on the same chimeric mouse model. RESULTS: The
      polymer delivery system released 80% of the loaded cisplatin in vivo over a 7-day
      period. The polymer-delivered cisplatin exhibited higher MTD (36 mg/kg) than free
      cisplatin (18 mg/kg) and had a statistically significant tumor suppression effect
      compared with free cisplatin when used at their respective MTD. CONCLUSIONS: The
      polymer delivery system can sustain cisplatin release for a period of 7 days. It
      can increase MTD and potentially enhance the antitumor efficacy of cisplatin
      against human head and neck cancers.

PMID- 12808660
TI  - Comprehensive head and neck oncology health status assessment.
AB  - BACKGROUND: This article presents the validation of the Head and Neck Cancer
      Inventory (HNCI), a health status assessment instrument with a small number of
      multiple-item domains that captures patients' ratings of functional status and
      attitude about that function. METHODS: The HNCI was administered to patients with
      upper aerodigestive tract carcinoma. An initial, cross-sectional study assessed
      feasibility and reliability. A subsequent, longitudinal study's factor analysis
      identified ineffective items and confirmed domain cohesiveness. Construct and
      criterion-related validity and sensitivity to detect change across time were
      evaluated. RESULTS: The HNCI was highly reliable. Criterion-related validity was
      demonstrated through comparisons with other HNC-specific instruments. Construct
      validity was demonstrated based on significant differences between patient groups
      (HNC/non-HNC, employment status, clinical stage, and type of treatment). Domain
      scores were sensitive to change across time. The domains' functional and
      attitudinal scores were significantly different. CONCLUSIONS: The HNCI is a
      reliable, valid instrument that evaluates the functional and attitudinal
      components of health status in HNC patients. This survey is recommended for self
      reported health status evaluation in HNC clinical trials.

PMID- 12808661
TI  - Effects of psychosocial intervention on quality of life in patients with head and
      neck cancer.
AB  - BACKGROUND: A longitudinal, prospective, case-control study evaluated if a
      psychosocial support program improved health-related quality of life (HRQL) in
      head and neck (H&N) cancer patients. METHODS: One hundred forty-four H&N cancer
      patients were included: 52 study patients and 92 controls. The study group met
      the support team repeatedly throughout the first year after diagnosis. HRQL was
      assessed three times during the first year and after 3 years using the EORTC QLQ
      C30, EORTC QLQ-H&N35, and HADS. RESULTS: A few statistically significant
      differences were found, all favoring the controls. Controls reported better
      global quality of life after 1 year and felt less ill after 3 years. Depression
      and treatment-related side effects were prevalent in both groups. CONCLUSIONS:
      Our psychosocial support program did not improve HRQL in H&N cancer patients. Its
      effectiveness may be improved by evaluating and actively integrating HRQL
      assessments during the program, thereby enabling rapid and adequate symptomatic
      treatment and/or psychologic intervention.

PMID- 12808662
TI  - Treatment outcome for synchronous locoregional failures of nasopharyngeal
      carcinoma.
AB  - BACKGROUND: To review the outcome and evaluate the prognostic factors in the
      treatment of synchronous locoregional failures of nasopharyngeal carcinoma (NPC).
      METHODS: We reviewed the records of 43 patients with synchronous locoregional
      failures of NPC who received salvage treatment or chemotherapy between November
      1986 and January 2001. The recurrent disease was stage II in 61%, stage III in
      30%, and stage IV in 9%. The local disease was rT1-2 in 67% and rT3-4 in 33%, and
      the regional disease was rN1 in 91% and rN2 in 9%. Persistent disease, defined as
      failures within 4 months of completion of primary radiotherapy, occurred in 53.5%
      and recurrent disease in 46.5%. Seventeen patients received surgery for regional
      and/or local failures with or without combined radiotherapy (ST group), 14
      patients received reirradiation to both local and regional disease (RT group),
      and 12 patients received palliative chemotherapy only (CT group). The median
      follow-up was 18 months (range, 4-153) and for the surviving patients it was 29
      months (range, 6-153). RESULTS: The 3-year relapse-free survival (RFS) rate and
      disease-specific survival (DSS) rate after salvage treatment or chemotherapy were
      17% and 38%, respectively. The 3-year RFS rates in stage II, III, and IV disease
      were 25%, 8%, and 0%, respectively. The corresponding 3-year DSS rates were 43%,
      28%, and 38%. The 3-year RFS rates in the ST, RT, and CT group were 39%, 7%, and
      0%, respectively. The corresponding 3-year DSS rates were 55%, 25%, and 25%.
      Patients whose local disease was treated by surgical resection had a 3-year local
      control rate of 71% compared with 38% by reirradiation using brachytherapy or
      external radiotherapy. For regional disease, the 3-year nodal control rate after
      radical neck dissection was 65% compared with 24% by reirradiation. Further
      locoregional failure represents the major failure pattern, and the proportion of
      patients who had further local, regional, and both locoregional failures were
      16%, 9%, and 53%, respectively. Distant metastasis occurred in 30% of patients,
      and only 5% had isolated distant metastasis in the absence of locoregional
      failures. On multivariate analysis, treatment by reirradiation or chemotherapy
      alone and rN2 disease were independent factors that predicted poor survival,
      whereas treatment by reirradiation or chemotherapy alone was the only independent
      factor that predicted further relapse or failure. CONCLUSIONS: Proper selection
      of patients for aggressive salvage treatment and individualization of treatment
      are important in managing patients with synchronous locoregional failures of NPC.
      A significant proportion of patients with early stage locoregional failures can
      still achieve long-term disease control and survival after aggressive salvage
      treatment using surgery with or without combined radiotherapy. In patients with
      more advanced disease, treatment by reirradiation alone or palliative
      chemotherapy is largely ineffective and is associated with a poor outcome.

PMID- 12808663
TI  - The beverage mate: a risk factor for cancer of the head and neck.
AB  - BACKGROUND: Mate is a tealike beverage consumed habitually in South America and
      among South Americans throughout the world. It is brewed from the dried leaves
      and stemlets of the perennial tree Ilex paraguariensis (yerba mate), a species
      that belongs to the Aquifoliaceae family. Mate consumption has been associated
      with an increased rate of oral, oropharyngeal, esophageal, and laryngeal cancers.
      The purpose of this study is to review the literature and discuss the role of
      Mate consumption as a risk factor for head and neck cancers. MATERIALS AND
      METHODS: We performed a thorough review of the relevant literature linking mate
      consumption with head and neck cancer and the proposed carcinogenicity of mate.
      Case control studies on mate-drinking populations and in vivo and in vitro
      studies on the carcinogenicity of mate were reviewed. The populations included in
      many of these studies also used alcohol and tobacco products, confounding the
      influence of mate as an independent risk factor. RESULTS: Evidence in the
      literature suggests that mate consumption is carcinogenic and plays a role in the
      development of cancers of the oral cavity, pharynx, larynx, and esophagus.
      CONCLUSIONS: The exact mechanism of carcinogenesis of mate is unknown. Both
      chemical and thermal carcinogenesis mechanisms have been suggested. Available
      information suggests that mate drinking is a risk factor for upper aerodigestive
      tract cancer.

PMID- 12808664
TI  - Total upper lip reconstruction with a free temporal scalp flap: long-term follow
      up.
AB  - BACKGROUND: In men, reconstruction of large full-thickness defects of the upper
      lip requires both an inner layer to replace the mucosal lining and an outer hair
      bearing layer. METHODS: When locating the superficial temporal vessels, the
      design of the temporal flap is marked following the hairline needed. After
      meticulously dissecting the flap, it is inset and microanastomosed with the
      facial blood vessels. The internal mucosal layer of the flap is grafted on.
      During the follow-up period, the sensory recovery and motor functions are
      examined and recorded. RESULTS: The postoperative courses were uneventful, and
      patients were satisfied with the results. One patient has a long follow-up period
      of 18 years. CONCLUSIONS: The free temporal scalp hair-bearing flap offers a
      reasonable alternative to conventional techniques in the reconstruction of large
      defects of the male upper lip or even a total upper lip. It is a single-staged,
      relatively simple method of providing hair-bearing skin to the upper lip.

PMID- 12808665
TI  - Myofibroblastoma of the larynx: a study of two cases.
AB  - BACKGROUND: We describe, for the first time, the occurrence of two pure examples
      of spindle cell neoplasm with fibrous and smooth muscle differentiation in the
      larynx. MATERIALS AND METHOD: Tissue sections from both tumors stained with
      hematoxylin and eosin were reviewed. Immunophenotypic analysis using keratin, S
      100 protein, SMA, and h-Caldesmon markers was performed. RESULTS: Tumors were
      seen as raised submucosal nodules in the glottic region of two elderly male
      patients. Histopathologically, the lesions were unencapsulated and composed of
      spindle cells that manifested variable cellular anaplasia and expressed SMA and
      were negative for keratin, S-100, and h-Caldesmon. CONCLUSIONS: We document
      histologically low-grade malignant myofibroblastic tumors of the larynx. Complete
      excision is advised.

PMID- 12808666
TI  - Liability in prenatal ultrasound screening.

PMID- 12808667
TI  - Vascular abnormalities of the uterus: have we recently over-diagnosed them?

PMID- 12808668
TI  - Short-term outcome of isolated and associated congenital heart defects in
      relation to antenatal ultrasound screening.
AB  - OBJECTIVE: To investigate the outcome of fetuses affected by congenital heart
      defects (CHD), either detected or undetected at ultrasound screening, according
      to their complexity and severity. DESIGN: The study group comprised 3633
      malformed fetuses entered into the Eurofetus database of which 798 had CHD. We
      compared the short-term outcome in cases where a CHD was detected by ultrasound
      screening with that in cases where a CHD was not detected. Isolated and
      associated CHD (ICHD and ACHD) and the degree of severity of defects were
      considered separately. Outcome data included termination of pregnancy (TOP),
      intrauterine fetal death, neonatal death (< 6 days after birth), gestational age
      at diagnosis and at delivery, mode of delivery and birth weight. RESULTS: Of the
      798 fetuses with CHD, 595 had ICHD and 203 had ACHD. The diagnosis of an anomaly
      was made significantly earlier in ACHD cases. TOP was chosen in 28% of cases with
      a prenatal diagnosis of CHD, 20% for ICHD and 37% for ACHD (P < 0.001). The
      survival rate of antenatally diagnosed fetuses was lower in those with ACHD than
      in those with ICHD (P < 0.001) and lower for fetuses with antenatal diagnosis
      than with postnatal diagnosis (P < 0.001); this was due to significant
      differences in the complexity and severity of the defect. Premature delivery (<
      32 weeks) was more frequent in fetuses in which an antenatal diagnosis of CHD had
      been made. Severe CHD were diagnosed earlier and were associated with a higher
      rate of TOP and spontaneous loss. CONCLUSIONS: The severity of CHD has a positive
      influence on the sensitivity of screening but a negative influence on the
      outcome. CHD that are not diagnosed antenatally include a high proportion of
      benign malformations. This explains the apparent paradox of a poorer outcome in
      fetuses in which a CHD was detected prenatally compared to those fetuses in which
      the defect was undetected prenatally. However, prenatal diagnosis provides
      parents with the option of TOP or of preventive care in specialized centers.

PMID- 12808669
TI  - Abnormal cardiac function in fetuses with increased nuchal translucency.
AB  - OBJECTIVE: To evaluate cardiac function in structurally and chromosomally normal
      fetuses with increased nuchal translucency (NT). METHODS: Forty-two structurally
      and chromosomally normal fetuses with increased NT at 11-14 weeks of gestation
      underwent fetal echocardiographic examination at 20-23 weeks. Fifty fetuses with
      normal NT values were considered as controls. Pulmonary and aortic peak velocity
      and time to peak velocities were measured as indices of ventricular systolic
      function. The ratios between the E-wave and A-wave (E/A) and the ratios between
      the E-wave and time velocity integral (E/TVI) at the level of both
      atrioventricular valves were evaluated as indices of ventricular diastolic
      function. RESULTS: In fetuses with increased NT the E/A ratios were significantly
      decreased when compared to control fetuses at the level of both the mitral (0.52
      +/- 0.09 vs. 0.60 +/- 0.10, P = 0.0002) and tricuspid (0.51 +/- 0.09 vs. 0.61 +/-
      0.09, P < 0.0001) valves. Similar results were found for the E/TVI ratios (mitral
      valve 4.79 +/- 1.03 vs. 5.63 +/- 1.23, P = 0.0007 and tricuspid valve 4.40 +/-
      0.88 vs. 5.19 +/- 0.82, P < 0.0001). No significant relationship was found
      between the degree of NT and the abnormalities in Doppler indices. There were no
      significant differences in Doppler systolic indices. CONCLUSION: Structurally and
      chromosomally normal fetuses with increased NT have low E/A and E/TVI ratios at
      20-23 weeks of gestation. These findings might indicate cardiac diastolic
      dysfunction.

PMID- 12808670
TI  - Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound
      examination across Europe.
AB  - OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine
      part of prenatal care in most European countries. The objective of this study was
      to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound
      examination. METHODS: Data from 20 registries of congenital malformations in 12
      European countries were included in the study. RESULTS: There were 2454 cases
      with congenital heart diseases, 479 of which were recognized syndromes, including
      375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty
      one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of
      1130 cases with renal anomalies were recognized syndromes, including 128
      chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them
      (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non
      chromosomal syndromes. Fifty-four of the 250 cases with limb defects were
      recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without
      chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally
      (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal
      wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with
      gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases
      with diaphragmatic hernia had recognized syndromes, including 20 chromosomal
      aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them
      (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal
      anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There
      were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP)
      including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes.
      Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%).
      Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed
      prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of
      them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed
      prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are
      associated with major congenital anomalies (cardiac, renal, intestinal, limb
      defects, abdominal wall defects and oral clefts) can be detected prenatally by
      the anomaly scan. However the detection rate varies with the type of syndrome and
      with the different countries' policies of prenatal screening.

PMID- 12808671
TI  - Ultrasound assessment of cervical length in threatened preterm labor.
AB  - OBJECTIVE: More than 70% of women presenting with threatened preterm labor do not
      progress to active labor and delivery. The aim of this study was to investigate
      the hypothesis that in women with threatened preterm labor, sonographic
      measurement of cervical length helps distinguish between true and false labor.
      METHODS: We examined 216 women with singleton pregnancies presenting with regular
      and painful uterine contractions at 24-36 (mean, 32) weeks of gestation. Women in
      active labor, defined by the presence of cervical dilatation > or = 3 cm, and
      those with ruptured membranes were excluded. On admission to the hospital a
      transvaginal scan was performed to measure the cervical length. The subsequent
      management was determined by the attending obstetrician. The primary outcome was
      delivery within 7 days of presentation. RESULTS: In 173 cases the cervical length
      was > or = 15 mm and only one of these women delivered within 7 days. In the 43
      cases with cervical length < 15 mm delivery within 7 days of presentation
      occurred in 16 (37%) including 6/14 (42%) treated with tocolytics and 10/29 (35%)
      managed expectantly. Logistic regression analysis demonstrated that the only
      significant contributor in the prediction of delivery within 7 days was cervical
      length < 15 mm (odds ratio = 101, 95% CI 12-800, P < 0.0001) with no significant
      contribution from ethnic group, maternal age, gestational age, body mass index,
      parity, previous history of preterm delivery, cigarette smoking, contraction
      frequency or use of tocolytics. CONCLUSIONS: In women with threatened preterm
      labor, sonographic measurement of cervical length helps distinguish between true
      and false labor.

PMID- 12808672
TI  - Cervical changes in twin pregnancies observed by transvaginal ultrasound during
      the latter half of pregnancy: a longitudinal, observational study.
AB  - OBJECTIVE: To determine what constitutes normal cervical changes in twin
      gestations during the latter half of pregnancy, and whether there are differences
      in the pattern of cervical change between women expecting twins giving birth at
      term (> or = 36 completed gestational weeks, GW) and preterm. METHODS: Twenty
      women (12 nulliparous, eight parous) expecting twins were examined with
      transvaginal ultrasound every week from 24 GW until delivery. Cervical length and
      width were measured, the inner cervical os was assessed as being closed or open,
      and any dynamic cervical changes were noted. Examination results were unavailable
      to the staff involved in the care of the women. RESULTS: Eight women (40%)
      delivered preterm spontaneously at 32-35 GW. Cervical length remained unchanged (
      approximately 10 mm) in one woman, who delivered preterm. It decreased in the
      remaining 19 women. The median shortening rate for women manifesting a continuous
      shortening of the cervix was 2.9 (0.8-5.2) mm/week in women giving birth preterm
      vs. 1.8 (0.8-2.4) mm/week in those who gave birth at term (P = 0.08). Median
      cervical length at the first examination was similar in women who delivered
      preterm and at term (39 vs. 41 mm), but at 32 GW the cervix was shorter in women
      who delivered preterm (median, 18 vs. 31 mm, P = 0.02). Cervical width remained
      unchanged in 63% (5/8) of the women who delivered preterm vs. 8% (1/12) of those
      who gave birth at term (P = 0.02). The cervix became wider in the remaining
      women. Median cervical width at the first examination was similar in women who
      delivered preterm and at term (38 vs. 38 mm), but in women who delivered preterm
      the cervix was thinner at 0-6 days before spontaneous start of labor (median, 40
      vs. 48 mm, P = 0.07). An opening of the inner cervical os was seen < or = 27 GW
      in 88% (7/8) of the women who delivered preterm vs. 17% (2/12) of those who
      delivered at term (P = 0.006), the corresponding figures for dynamic changes
      being 63% (5/8) vs. 17% (2/12) (P = 0.06). Dynamic changes were seen in a greater
      proportion of the examinations in women who delivered preterm (median, 25% vs.
      4%, P = 0.07). CONCLUSIONS: The pattern of cervical changes from 24 GW to
      delivery differs between twin pregnancies delivering preterm (at 32-35 GW) and at
      term (> or = 36 GW). In twin pregnancies delivered preterm cervical shortening is
      more rapid, the cervix does not broaden to the same extent as in twins delivered
      at term, an open inner cervical os and dynamic cervical changes are seen earlier
      in gestation, and dynamic cervical changes are seen more often. Cervical changes
      in women with twins who give birth as early as at 24-31 GW may be different.

PMID- 12808673
TI  - Prenatal detection of velamentous insertion of the umbilical cord: a prospective
      color Doppler ultrasound study.
AB  - OBJECTIVE: Velamentous insertion of the umbilical cord, with a reported incidence
      of 1% in singleton pregnancies, has been associated with several obstetric
      complications including fetal growth restriction, prematurity, congenital
      anomalies, low Apgar scores, fetal bleeding and retained placenta. The aim of
      this study was to determine the feasibility of identifying velamentous insertion
      of the umbilical cord during routine obstetric ultrasound. DESIGN: This was a
      prospective, cross-sectional ultrasound study in 832 unselected second- and third
      trimester singleton pregnancies. Color Doppler ultrasound was routinely performed
      to identify the placental cord insertion site. The role of three-dimensional (3D)
      ultrasound in evaluating the placental cord insertion site was also studied in a
      subset of 50 pregnancies from this population. RESULTS: The placental cord
      insertion site was identified in 825/832 (99%) cases. Visualization was not
      achieved in seven third-trimester pregnancies with a posterior placenta. A
      velamentous insertion was suspected prenatally in eight cases, seven of which
      were confirmed after delivery as velamentous and one as markedly eccentric
      (battledore placenta). 3D ultrasound performed poorly at evaluating placental
      cord insertion site, being less efficient due to poor-quality resolution and far
      more time-consuming than the combined use of gray-scale and color Doppler
      ultrasound. CONCLUSIONS: Velamentous insertion of the umbilical cord can reliably
      be detected prenatally by gray-scale and color Doppler ultrasound. 3D imaging had
      limited value in the evaluation of the placental cord insertion site in our
      subset of patients. Systematic assessment of the placental cord insertion site at
      routine obstetric ultrasound has the potential of identifying pregnancies with
      velamentous insertion and, therefore, those at risk for obstetric complications
      including vasa previa.

PMID- 12808674
TI  - Color Doppler imaging is a valuable tool for the diagnosis and management of
      uterine vascular malformations.
AB  - OBJECTIVE: The aim of this study was to assess the spontaneous outcome of uterine
      vascular malformations detected with ultrasonography and color Doppler, and to
      investigate the predictive value of color Doppler imaging as to which patients
      require invasive treatment. METHODS: This was a prospective observational study
      conducted between January 1999 and February 2001 comprising all consecutive
      patients diagnosed with a uterine vascular malformation by ultrasonography and
      color Doppler imaging. Spectral analysis included measurement of flow velocities,
      pulsatility index (PI) and resistance index (RI). Close follow-up was arranged in
      all cases and the outcomes were recorded. RESULTS: A total of 30 consecutive
      patients with uterine vascular malformations were included in the study. Spectral
      analysis of the vessels in the vascular malformations within the myometrium and
      endometrium revealed the presence of a low-impedance and high-velocity flow. The
      average values for PI, RI, peak systolic velocity (PSV) and time-averaged maximum
      velocity (TAMXV) were 0.50, 0.38, 0.63 m/s and 0.46 m/s, respectively. Eight
      patients (27%) eventually required embolization of the uterine arteries and three
      of them had true arteriovenous malformations confirmed at angiography. PSV values
      of >/= 0.83 m/s were associated with higher probabilities of further treatment,
      such as an embolization, whereas no vascular malformation with a PSV value < 0.39
      m/s required embolization. CONCLUSION: Conservative management is possible in
      more than two-thirds of patients presenting with uterine vascular malformations
      diagnosed by color Doppler sonography. Despite considerable overlap, PSV values
      appear to be useful in distinguishing between low- and high-risk patients.

PMID- 12808675
TI  - Reproducibility of three-dimensional ultrasound diagnosis of congenital uterine
      anomalies.
AB  - OBJECTIVE: To examine the reproducibility of the diagnosis of congenital uterine
      anomalies and the repeatability of measurements of uterine cavity dimensions
      using three-dimensional (3D) ultrasound. METHODS: The reproducibility of
      diagnosis of congenital uterine anomalies was examined by re-slicing stored 3D
      ultrasound volumes. Each data set was evaluated by two independent observers.
      Assessment of uterine morphology was performed in a standardized plane, with the
      interstitial portions of the Fallopian tubes used as reference points.
      Additionally, in 35 cases of congenital uterine anomalies the width of the
      uterine cavity (W), fundal distortion (F) and the length of unaffected uterine
      cavity (C) were measured. Intraobserver and interobserver variabilities were
      evaluated by each observer performing all three measurements twice. RESULTS:
      Eighty-three 3D ultrasound volumes were examined. Both operators classified 27
      uteri as normal, 33 as arcuate, 19 as subseptate and three as unicornuate. A
      single case of uterine anomaly was described as arcuate uterus by one operator
      and subseptate by another (kappa 0.97). The intraobserver variability for each of
      the three measurements (W, F and C) was satisfactory with limits of agreement
      ranging from +/-1.43 to +/-2.51 mm. The examination of the interobserver
      variability showed no significant differences between the two observers (F =
      0.484, P > 0.05). CONCLUSION: 3D ultrasound is a reproducible method for the
      diagnosis of congenital uterine anomalies and for the measurement of uterine
      cavity dimensions.

PMID- 12808676
TI  - Endometrial blood flow mapping using transvaginal power Doppler sonography in
      women with postmenopausal bleeding and thickened endometrium.
AB  - OBJECTIVE: To evaluate the role of transvaginal power Doppler sonography to
      discriminate between benign and malignant endometrial conditions in women
      presenting with postmenopausal bleeding and thickened endometrium at baseline
      sonography. METHODS: Ninety-one postmenopausal women (median age, 58 years;
      range, 47-83 years) presenting with uterine bleeding and a thickened endometrium
      (> or = 5-mm double-layer endometrial thickness) on transvaginal sonography were
      included in this prospective study. Endometrial blood flow distribution was
      assessed in all patients by power Doppler immediately after B-mode transvaginal
      sonography. Three different vascular patterns were defined: Pattern A: multiple
      vessel pattern, Pattern B: single-vessel pattern and Pattern C: scattered-vessel
      pattern. Histological diagnoses were obtained in all cases. No patient taking
      tamoxifen citrate or receiving hormone replacement therapy was included. RESULTS:
      Histological diagnoses were as follows: endometrial cancer: 33 (36%), endometrial
      polyp: 37 (41%), endometrial hyperplasia: 14 (15%), endometrial cystic atrophy: 7
      (8%). Blood flow was found in 97%, 92%, 79% and 85% of cases of carcinoma, polyp,
      hyperplasia and endometrial cystic atrophy, respectively. A total of 81.3% of
      vascularized endometrial cancers showed Pattern A, 97.1% of vascularized polyps
      exhibited Pattern B and 72.7% of vascularized hyperplasias showed Pattern C.
      Sensitivity and specificity for endometrial cancer were 78.8% and 100%. For
      endometrial polyp these respective values were 89.2% and 87% and for hyperplasia
      they were 57.1% and 88.3%. CONCLUSIONS: Transvaginal power Doppler blood flow
      mapping is useful to differentiate benign from malignant endometrial pathology in
      women presenting with postmenopausal bleeding and thickened endometrium at
      baseline sonography.

PMID- 12808677
TI  - Three-dimensional ultrasound imaging of the pelvic floor: the effect of
      parturition on paravaginal support structures.
AB  - OBJECTIVE: It is assumed that support of the female urethra and bladder is
      maintained by paraurethral and paravaginal fascial structures, with hypermobility
      resulting from delivery-related trauma. This study used three-dimensional
      translabial ultrasound to assess these structures and document peripartal
      changes. DESIGN: A clinical observational pilot study was performed on 26
      nulliparous women recruited in the third trimester of pregnancy. They underwent
      translabial two- and three-dimensional ultrasound. Twenty-three women were again
      seen 2-5 months postpartum. The assessor was blinded against two-dimensional
      ultrasound and delivery data. Vaginal tenting was rated as being present,
      indeterminate or absent at each of three levels, and was correlated with bladder
      neck descent (BND) and urethral rotation on Valsalva maneuver. RESULTS: Tenting
      was visible at all levels in 21 of 26 women antepartally. In three women tenting
      was absent on one level; in two cases tenting was rated indeterminate. There was
      no significant difference in BND between women with visible tenting and those
      without. The BND range for women with intact tenting was 5.4-41.6 mm. Twenty-one
      of the 26 women were included in the postpartum analysis. Of these, obvious
      peripartal changes were documented in five. Loss of tenting did not correlate
      significantly with changes in BND. CONCLUSIONS: Most nulliparous women showed
      evidence of intact paravaginal support structures. Tenting occurred in women with
      widely varying BND, implying that excess bladder neck mobility may be due to
      increased fascial compliance. Postnatally, fascial disruption was suspected in a
      minority of patients only. In some women delivery-related changes may be due to
      attenuation rather than disruption of structures.

PMID- 12808678
TI  - Nuchal translucency thickness measurement: repeatability using a virtual
      ultrasound scanner.
AB  - AIM: To use a PC-based virtual ultrasound scanner (VirUS) in the investigation of
      inter- and intraoperator nuchal translucency (NT) thickness measurement
      repeatability of experienced ultrasound operators. METHODS: Realistic fetal
      ultrasound images of defined NT thickness were simulated with VirUS with
      emulation of scanner gain and time-gain compensation and gain-dependent echo size
      changes. A set of 50 images was generated with uniformly distributed NT thickness
      (range, 1-5 mm at 1-mm intervals) and translucency angle (mean +/- standard
      deviation of +/- 2.52 degrees +/- 1.85 degrees about the horizontal). Operators
      (n = 13) measured NT thickness in the image set on three occasions separated by
      at least 1 day, giving 150 measurements per operator (total measurements, 1950).
      RESULTS: Inter- and intraoperator repeatabilities were +/- 0.41 mm and +/- 0.22
      mm, respectively (at the 95% confidence level). There were significant
      correlations between repeatability and mean measured NT thickness (r = - 0.72, P
      = 0.005 at 4-mm interval), between gain and mean measured NT thickness (P </=
      0.002, n = 8/13) and between gain and repeatability coefficient (P < 0.01, n =
      6/13). DISCUSSION: VirUS provides a consistent NT audit environment and
      demonstrates the need to both optimize repeatability vs. mean measured thickness
      and to set gain consistently. The technique has potential in operator training.

PMID- 12808679
TI  - Arteriovenous malformation of the uterus associated with secondary postpartum
      hemorrhage.
AB  - We present the case of a young woman with persistent secondary postpartum
      hemorrhage. Transvaginal imaging demonstrated an irregular pulsatile lesion in
      the anterior myometrium. Color Doppler analysis revealed the presence of abnormal
      vessels consistent with an arteriovenous malformation. Typically this vascular
      abnormality had a turbulent pattern of arterial and venous flow with high peak
      velocities and low resistance. The patient was treated with selective arterial
      embolization leading to a full recovery.

PMID- 12808680
TI  - Ultrasound diagnosis of uterine arteriovenous fistula associated with placental
      site trophoblastic tumor.
AB  - We report a case of a woman with abnormal vaginal bleeding who had a placental
      site trophoblastic tumor (PSTT) detected following hysterectomy. Surgery was
      performed because of a large uterine arteriovenous fistula detected by
      transvaginal color and pulsed Doppler sonography. Color Doppler sonography
      revealed a lacunar-type lesion with a marked increase in uterine vascularity, and
      pulsed Doppler sonography demonstrated a low resistance index. This vascular
      pattern indicated the formation of blood lacunae and arteriovenous shunts caused
      by PSTT within the uterine myometrium. This is the first report to describe the
      ultrasound findings in a case of PSTT complicated by a uterine arteriovenous
      fistula.

PMID- 12808681
TI  - Multiple fetal anomalies associated with subtle subtelomeric chromosomal
      rearrangements.
AB  - We report two cases of multiple fetal anomalies detected by prenatal ultrasound
      and associated with subtle subtelomeric chromosomal rearrangements. The first
      case presented at 25 weeks of gestation with an enlarged cisterna magna and
      ventriculomegaly. Karyotyping of amniocytes showed a subtle terminal abnormality
      of chromosome 6q. Thereafter, screening of all unique chromosomal subtelomeric
      regions using a panel of telomere-specific, fluorescence in situ hybridization
      (FISH) probes revealed an unbalanced reciprocal translocation between 6q and 17p
      [46,XX.ish der(6)t(6;17)(q25.3;p13)(TelVysion6q-;TelVysion17p+)]. The second case
      presented at 25 weeks of gestation with tetralogy of Fallot and at 34 weeks of
      gestation had additional ultrasound findings of an arachnoid cyst and
      intrauterine growth restriction. Postnatal karyotyping of peripheral blood was
      performed and appeared normal. However, a cryptic deletion of the subtelomeric
      region of the long arm of chromosome 14 was identified when the infant's blood
      sample was used as a control for an oncology FISH probe. Thereafter, screening of
      all unique chromosomal subtelomeric regions using a panel of telomere-specific
      FISH probes revealed an unbalanced reciprocal translocation of chromosomes 14q
      and 20p [46,XY.ish der(14)t(14;20)(q32.3;p13)(IGH-, D14S308-,TelVysion20p+)mat].
      These two cases add to a growing number of reports of cryptic subtelomeric
      chromosomal rearrangements associated with congenital anomalies. This is the
      first report of multiple, simultaneous FISH screening of the subtelomeric regions
      in amniotic fluid and has demonstrated the technical feasibility of this
      technique in the prenatal period.

PMID- 12808682
TI  - First-trimester diagnosis of micrognathia as a presentation of Pierre Robin
      syndrome.
AB  - We describe a case of first-trimester diagnosis of micrognathia. A transvaginal
      ultrasound scan performed at 13 weeks' gestation revealed an abnormal fetal
      facial profile consisting of a small mandible and a receding chin. A subsequent
      amniocentesis at 15 weeks' gestation revealed a normal karyotype. A morphology
      scan and subsequent postmortem examination at 19 weeks confirmed the first
      trimester findings and revealed, in addition to the facial pathology, a complex
      cardiac abnormality and unilateral talipes equinovarus. These findings are
      consistent with the diagnosis of Pierre Robin syndrome.

PMID- 12808683
TI  - Prenatal diagnosis of congenital megalourethra associated with VACTERL sequence
      in twin pregnancy: favorable postnatal outcome.

PMID- 12808684
TI  - Cervical pregnancy: transvaginal sonographic diagnosis and conservative surgical
      management after failure of systemic methotrexate.

PMID- 12808685
TI  - Is reduction in size pathognomonic of functional ovarian cysts?

PMID- 12808686
TI  - Transvaginal sonographic appearance of anaerobic endometritis.

PMID- 12808687
TI  - Variable umbilical artery end-diastolic frequency is associated with arterio
      arterial anastomosis.

PMID- 12808688
TI  - Sonography for the diagnosis of adenomyosis.

PMID- 12808689
TI  - Three-dimensional ultrasonographic imaging of cleft lip: the winners are the
      parents.

PMID- 12808691
TI  - Competency to stand trial: rationalism, "contextualism" and other modest
      theories.
AB  - Determinations of competency to stand trial in criminal cases are complicated and
      rendered unpredictable by two sub-surface issues that are rarely articulated: (i)
      the place of the defendant's rationality in the substantive standard(s) for
      competency and (ii) the level or degree of incompetency required to stop the
      criminal process. The rare references to these issues, mostly indirect, that are
      made in the cases, commentary, and competency testing instruments devised
      (including those civil as well as criminal) are examined. The conclusion that
      emerges is that the level of capacity and rationality required of the defendant
      depends much on context-the type of case, its relative complexity, and the values
      and stakes implicated in the outcome.

PMID- 12808692
TI  - Beyond Dusky and Godinez: competency before and after trial.
AB  - Scholars have carefully considered all aspects of the incompetency to stand trial
      process, questions involving incompetency to confess, questions involving
      incompetency to be executed, and, to a lesser extent, questions related to
      incompetency to plead guilty or to waive counsel, but little attention has been
      paid to the relationship between incompetency and the full range of other
      criminal procedure issues: sentencing, appeals, consent to searches, and others.
      This article discusses this range of issues, assesses the factors relied upon by
      courts in deciding these cases and attempts to offer an agenda for future
      scholarly developments in this area.

PMID- 12808693
TI  - Involuntary competence.
AB  - This article addresses whether the state has the right to medicate involuntarily
      a defendant who is incompetent either to plead guilty or to stand trial for the
      purpose of restoring legal competence. It first presents the constitutional
      background concerning incompetence and the right of prisoners generally to refuse
      psychotropic medication. Then the article examines the individual and state
      interests that must be considered to decide specifically whether the state may
      involuntarily medicate a criminal defendant solely for the purpose of restoring
      competence. Although the individual interests are strong, the article contends
      that the state does have a right to medicate involuntarily defendants charged
      with most crimes to restore trial competence, and that adequate remedies are
      available to ensure that medicated defendants receive a fair trial.

PMID- 12808694
TI  - Five year research update (1996-2000): evaluations for competence to stand trial
      (adjudicative competence).
AB  - This article reviews and evaluates publications during 1996-2000 with relevance
      for assessments of competence to stand trial (also known as adjudicative
      competence). The review focuses specifically on articles that provide new
      concepts or data supported by research or case analyses. The studies are reviewed
      under the following headings: (i) the systemic context of evaluations of
      adjudicative competence (AC); (ii) conceptual guidelines for AC evaluations;
      (iii) research on AC assessment methods; (iv) empirical correlates of AC
      judgments and psycholegal abilities; (v) quality of AC evaluations and reports;
      (vi) interpretation of AC evaluation data; (vii) issues in AC assessment of
      special populations (e.g., juveniles, persons with mental retardation, and
      women); and (viii) treatment to restore competence. Suggestions are offered for
      further research to advance the quality of clinical evaluations of adjudicative
      competence.

PMID- 12808695
TI  - Issues and considerations regarding the use of assessment instruments in the
      evaluation of competency to stand trial.
AB  - Since the early 1960s, a number of instruments, reflecting a broad range of
      assessment methods, have been developed to assist in the evaluation of competency
      to stand trial. These instruments have taken various forms including checklists,
      self-report questionnaires, sentence-completion tasks, and interview-based
      instruments with and without criterion-based scoring. This article reviews these
      assessment instruments with a specific focus on their contribution to the
      competency evaluation process. Furthermore, relevant issues and considerations
      regarding the use of these instruments are outlined, including a comparison of
      screening versus assessment applications of these instruments, balancing
      standardized approaches with individualized assessments, the integration of
      instrumentally derived data with other components of a competency evaluation, and
      the communication of results to the fact finder. Each of these issues is
      discussed in relation to specific competency assessment instruments. Overall, we
      argue that each of the competency assessment instruments developed to date can
      make a contribution to the competency evaluation process and this article serves
      to delineate those areas in which these contributions are made.

PMID- 12808696
TI  - Hospitalization of criminal defendants for evaluation of competence to stand
      trial or for restoration of competence: clinical and legal issues.
AB  - The clinical and legal literature abounds with articles dealing with competence
      to stand trial; while most agree that criminal defendants must be capable of
      defending themselves before the state can bring them to trial, a number of
      articles are quite critical of the procedures by which these concepts are
      operationalized, some even going so far as to suggest abolishing the requirement
      for competence altogether. One of the major problems leading to the criticisms is
      the unnecessary loss of liberty involved. Although the length of incarceration
      has decreased significantly since the 1970s, the majority of states still permit,
      or require, hospitalization for evaluation of competence, and even more so for
      treatment to restore competence. The author reviews case law and presents data
      from his survey of current state statutes and responses from state forensic
      mental health program directors, to demonstrate the rarity of outpatient
      treatment to restore competence. He argues that outpatient treatment for
      defendants who do not require hospitalization on clinical or public safety
      grounds should be available, on both clinical and legal grounds, and provides
      recommendations for establishing such programs in the community.

PMID- 12808697
TI  - Pre-adjudicative and adjudicative competence in juveniles and young adults.
AB  - There are several different types of legal competence, such as competence to
      waive Miranda rights, competence to confess, and competence to stand trial.
      Although it can be surmised that many of the underlying factors that influence
      the different legal competencies are similar, little research has been conducted
      to empirically test this hypothesis. In the present study, juveniles' and young
      adults' understanding and appreciation of their Miranda rights and their ability
      to stand trial were measured. Age, suggestibility, average grades in school, and
      frequency of previous police involvement were also examined as possible factors
      that influence both types of legal knowledge. Results indicated that Miranda
      competence and adjudicative competence are indeed strongly related, especially
      for juveniles. Also, age and suggestibility were found to predict Miranda
      competence, whereas suggestibility and average school grades predicted competence
      to stand trial. Patterns of findings often diverged for juveniles and young
      adults. Implications for legal policy are discussed.

PMID- 12808698
TI  - Lessons learned.

PMID- 12808699
TI  - Clinical and urodynamic features of intrinsic sphincter deficiency.
AB  - AIMS: A prospective analysis of 92 patients with genuine stress incontinence was
      performed to identify the clinical and urodynamic features of intrinsic sphincter
      deficiency (ISD). METHODS: We divided the patients into two categories: 50
      patients affected by pure ISD as they had severe stress incontinence and no
      urethral mobility; 42 patients suffering from stress urinary incontinence without
      ISD as they had mild stress incontinence and marked urethral hypermobility.
      Cystometry was normal in all patients. The presence/absence of ISD was considered
      the dependent variable and was correlated against the following independent
      variables: age, vaginal deliveries, menopause, previous urogynecological surgery
      and/or hysterectomy, supine stress test, irritative and/or obstructive symptoms,
      Valsalva leak point pressure (VLPP), maximum urethral closure pressure (MUCP),
      urethral functional length (UFL), and leakage during cystometry. RESULTS: The
      statistical analysis showed close correlations between ISD and age (P < 0.001),
      menopausal status (P < 0.001), previous surgery (P < 0.0001), supine stress test
      (P < 0.0001), leakage during cystometry (P < 0.001), and UFL (P < 0.01). The VLPP
      was below the cut-off value (</=60 cm H(2)O) in 70% of ISD patients (P < 0.0001),
      whereas the MUCP in 50% of ISD patients (P < 0.0001). Multiple logistic analysis
      showed that lower VLPP, lower MUCP, and previous surgery correlate more
      significantly with ISD. After backward conditional stepwise logistic regression,
      the odds ratio of having ISD were VLPP = 2.3, MUCP = 7.7, VLPP + MUCP = 62.8.
      CONCLUSIONS: ISD is related to the presence of a more severe clinical picture and
      case history, but the most significant independent variables are the VLPP and
      MUCP.

PMID- 12808700
TI  - Compliance of the bladder neck supporting structures: importance of activity
      pattern of levator ani muscle and content of elastic fibers of endopelvic fascia.
AB  - AIMS: Firm bladder neck support during cough, suggested to be needed for
      effective abdominal pressure transmission to the urethra, might depend on
      activity of the levator ani muscle and elasticity of endopelvic fascia. METHODS:
      The study group of 32 patients with stress urinary incontinence and hypermobile
      bladder neck, but without genitourinary prolapse, were compared with the control
      group of 28 continent women with stable bladder neck. The height of the bladder
      neck (HBN) and compliance of the bladder neck support (C) were assessed, the
      latter by the quotient of the bladder neck mobility during cough and the change
      in abdominal pressure. By using wire electrodes, the integrated full-wave
      rectified electromyographic (EMGave) signal of the levator ani muscle was
      recorded simultaneously with urethral and bladder pressures. The pressure
      transmission ratio (PTR), time interval between the onset of muscle activation
      and bladder pressure increment (DeltaT), and area under the EMGave curve during
      cough (EMGcough) were calculated. From bioptic samples of endopelvic fascia
      connecting the vaginal wall and levator ani muscle, elastic fiber content was
      assessed by point counting method. Mann-Whitney test was used to compare all the
      variables. Correlations between the parameters were evaluated by using the
      Spearman correlation coefficient. RESULTS: In the study group, HBN was
      significantly lower (P < 0.001), C was significantly greater (P < 0.001), and PTR
      was significantly lower (P < 0.001). In the study group, the muscular activation
      started later (median, DeltaT(l), -0.147 second; DeltaT(r), -0.150 second), and
      in the control group, it preceded (DeltaT(l), 0.025 second; P < 0.001; DeltaT(r),
      0.050 second; P < 0.001) the bladder pressure increment. EMGcough on the left
      side was significantly greater in the study group (P < 0.046). Elastic fiber
      content showed no difference between the groups. The analysis of all patients
      revealed negative correlations between C and PTR (r = -0.546; P < 0.001) and
      between C and DeltaT(l) (r = -0.316; P < 0.018). CONCLUSIONS: Firm bladder neck
      support enables effective pressure transmission. Timely activation of the levator
      ani seems to be an important feature.

PMID- 12808701
TI  - Predicting urethral area from video-urodynamics in women with voiding
      dysfunction.
AB  - AIMS: Mathematical models are useful for developing predictive parameters for
      characterizing the biomechanics of voiding dysfunction. The goal of this project
      was to test a one-dimensional steady flow model used to predict the minimum cross
      sectional urethral area from urodynamic data. METHODS: Nine adult female subjects
      underwent video-urodynamic testing. By using Bernoulli's formula and the
      Torricelli theorem, the minimum urethral area was predicted from pressure and
      flow rate at the moment of maximum flow rate during voiding. This prediction was
      compared with the minimum cross-sectional area of the urethra, which was
      calculated from minimum urethral diameter as measured from fluoroscopy, assuming
      a circular cross-section. RESULTS: The maximum flow rate during voiding was 14.4
      +/- 3.0 mL/sec. Mean bladder, abdominal, and detrusor pressures simultaneous with
      maximum flow rate were 63 +/- 7, 29 +/- 6, and 33 +/- 6 cm H(2)O, respectively.
      Mean minimum cross-sectional area of the urethra from fluoroscopy was 8.0 +/- 2.0
      mm(2). Mean minimum cross-sectional area of the urethra predicted by the
      mathematical model was 5.0 +/- 1.0 mm(2) using bladder pressure and 7.0 +/- 2.0
      mm(2) using detrusor pressure. There were no significant differences between the
      three cross-sectional area measures. However, when area predictions were
      expressed as percentage of fluoroscopic measurements, the estimate from detrusor
      pressure (97 +/- 13%) was significantly larger than the estimate from bladder
      pressure (69 +/- 7%). CONCLUSIONS: A steady flow model is accurate enough on
      average to describe urine flow in the urethra. However, it may not be
      sufficiently accurate to aid in diagnosis of individuals.

PMID- 12808702
TI  - Effectiveness of pelvic floor muscle exercise therapy supplemented with a health
      education program to promote long-term adherence among women with urinary
      incontinence.
AB  - AIMS: A longitudinal randomized controlled trial (RCT) was conducted to evaluate
      the effectiveness of physiotherapeutic pelvic floor muscle exercise (PFME)
      therapy supplemented with a health education program to promote long-term
      adherence among women with stress, mixed, and urge urinary incontinence (UI).
      METHODS: Women (n = 129) were evaluated by their general practitioner (GP) and
      randomized in either the control group (PFME therapy alone) or one of the three
      experimental groups (PFME therapy with one of the three health education program
      versions). Therapy consisted of 9-18 individual 30 min sessions with a
      specialized physiotherapist, over 14-22 weeks. Outcome measures were weekly
      frequency of wet episodes and adherence behavior. Women were assessed up to 1
      year after therapy. RESULTS: The health education program had no additional
      impact to individual contact during PFME therapy on treatment outcome, nor on
      adherence. However, the individual physiotherapeutic treatment protocol was very
      effective in reducing weekly frequency of wet episodes from 23 to 8 times a week
      immediately after therapy, and effects were maintained during the 1-year follow
      up period. Adherence was very high; most women followed the behavioral advice on
      average 6 days/week at posttest and still 4-5 days 1 year after therapy. Results
      were not different between incontinence types. Women who had relatively frequent
      wet episodes before and 1 year after therapy had higher adherence levels compared
      to women who had fewer weekly losses. CONCLUSIONS: Results suggest that a
      standardized protocol checklist for physiotherapists covering all treatment
      aspects of PFME therapy, may optimize long-term treatment outcome and adherence
      behavior among patients, and outshines the addition of a health education
      program.

PMID- 12808703
TI  - Inter-observer agreement in the estimation of bladder pressure using a penile
      cuff.
AB  - AIMS: Objective data are useful in quantifying a patient's lower urinary tract
      symptoms (LUTS). We are investigating the use of an inflatable penile cuff to
      obstruct flow progressively during voiding, and thereby determine the pressure
      p(cuff,int) at which flow is interrupted. The aim of this study was to determine
      the agreement between experienced observers in their estimates of p(cuff,int).
      METHODS: We recorded 486 cuff inflation cycles during 142 voids from 42 subjects
      recruited from urology out-patient's and prostate assessment clinics. Each
      inflation cycle was assessed independently by three experienced observers, a
      total of 1,458 ratings. According to our standard assessment procedure, the
      observers (i) indicated whether the inflation should be analyzed, (ii) estimated
      p(cuff,int) for those inflation cycles judged suitable for analysis, and (iii)
      discarded measurements that were clearly inconsistent with others from the same
      voiding cycle. RESULTS: Overall, 689 of the 1,458 ratings (45%) were excluded,
      with just 4% of all ratings discarded for inconsistency. For 385 of the 486
      inflation cycles (79%) there was complete agreement that the cycle should or
      should not be analyzed. Thereafter, for the 262 inflation cycles analyzed by two
      or three observers, the overall SD error in measurements of p(cuff,int) was 4.6
      cm H(2)O. CONCLUSIONS: We conclude that there is good agreement between
      experienced observers in their interpretation of data from the cuff test. For
      practical purposes, there is no need for multiple observers in the clinical
      application of the cuff method.

PMID- 12808704
TI  - Clinical diagnosis of bladder outlet obstruction in men with lower urinary tract
      symptoms: reliability of commonly measured parameters and the role of idiopathic
      detrusor overactivity.
AB  - AIMS: There is no generally accepted consensus how to evaluate patients with
      lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction
      (BOO). We have tried to determine whether the most frequently used objective
      variables as prostate volume, IPS-score, maximum flow rate, residual urine
      volume, functional bladder capacity, and pressure-flow study are reliable for
      diagnosis of BOO and we investigated the influence of idiopathic detrusor
      overactivity (IDO) on this condition. METHODS: A total of 153 men with LUTS and
      suspected BOO were systematically examined with routine investigation including
      digital rectal examination, transrectal ultrasound (TRUS), post-void residual
      urine volume measurement, uroflowmetry, and pressure-flow study. All patients
      completed IPS-score. Patients were divided into groups based on Schafer's grade
      of obstruction and incidence of IDO and clinical and urodynamical variables were
      compared. RESULTS: At baseline, 45.8% of the patients were urodynamically
      moderately obstructed and 37.9% were found to be severely obstructed. The grade
      of obstruction did not correlate with age. Prostate volume, post-void residual
      volume (PVR), and maximum flow rate correlated significantly with the degree of
      obstruction. The mean IPS-score remained almost unchanged throughout all
      obstruction groups. The incidence of IDO was 40.5% and increased from 16% in the
      minor obstruction group to 38.6% and 53.4% in the moderate and severe obstruction
      group, respectively. The patients with IDO were older, had larger prostates and
      were more obstructed. There was no impact of IDO on symptomatology of BOO.
      CONCLUSIONS: These data indicate that IPS-score does not achieve sufficient
      diagnostic accuracy and its role in the assessment of BOO is limited. The grade
      of obstruction is more related to prostate volume, PVR, and maximum flow rate.
      BOO and IDO seem to be related and have numerous mutual interactions.

PMID- 12808705
TI  - Motor evoked potentials from the striated urethral sphincter and puborectal
      muscle: normative values.
AB  - AIMS: Transcranial magnetic stimulation enables the study of corticospinal motor
      pathways through evoked potential testing. By separate stimulation of cortical
      centers and spinal roots, it is possible to test motor conduction times
      segmentally. This method enables the localization of central or peripheral
      demyelinating neuropathies. As lower urinary tract dysfunction often accompanies
      these diseases, we wanted to present normative data for the motor innervation of
      the external urethral sphincter (EUS) and the puborectal muscle (PR). METHODS:
      Thirty healthy women without evidence of neurologic or lower urinary diseases
      were studied. They had a mean age of 52 years. Transcutaneous magnetic
      stimulations were applied to the vertex, the upper lumbar spine, and the sacrum.
      Evoked potentials were recorded with concentric needle electrodes placed in the
      EUS and the PR by a transvaginal route. Stimulations were performed with relaxed
      pelvic floor and with tonic contraction (facilitated responses). At least three
      responses were recorded for each modality. Stepwise multiple regression analysis
      was performed to test for the effect of age, height, body mass index, vaginal
      parity, and menopause. RESULTS: In some subjects, it was only possible to record
      cortical latencies with facilitation. Technical difficulties were encountered
      with spinal stimulations. Reference values are presented as means with 95%
      confidence intervals. Regression analysis revealed height as a dependent factor
      for sacral latencies. CONCLUSIONS: Our data can serve as reference values for
      future studies of the fast conducting fibers in patients with sphincter
      dysfunction. The height of the patient should be taken into account. The clinical
      applicability of the method is questionable.

PMID- 12808706
TI  - Clinical value of combined electrophysiological and urodynamic recordings to
      assess sexual disorders in spinal cord injured men.
AB  - AIMS: To assess the significance of combined neurophysiological and
      neurourological examinations for diagnosis of neurogenic male sexual dysfunction.
      METHODS: This is a prospective study of 32 spinal cord injured men. Each
      underwent clinical and neurophysiological examinations (sympathetic skin
      responses (SSR), pudendal somato-sensory evoked potentials (P-SSEP),
      bulbocavernosus reflex (BCR)) and neuro-urological measurements (urodynamic
      examination (UE), reflex erections (RE), psychogenic erections (PE) and nocturnal
      penile tumescence recordings (NPTR)). RESULTS: Erectile dysfunction due to
      impairment of RE was associated with loss of BCR and detrusor areflexia (P >
      0.001), whereas that due to impairment of PE was associated with loss of perineal
      SSR (P < 0.001). P-SSEP corresponded in 94% with impairment of penile sensibility
      and duration of erections in NPTR. The NPTRs were less related to functional
      sexual impairment. NPTRs in complete and incomplete suprasacral (level > T10)
      spinal lesion showed sufficient erections despite strongly disturbed PE. NPTRs in
      lumbosacral lesion revealed significant reduction in or absent erections and
      underestimated the presence of well excitable PE. CONCLUSIONS: Combined
      neurophysiologic and neurourologic testing provides highly relevant diagnostic
      informations about sexual dysfunction in men with spinal cord injury. Loss of the
      BCR and detrusor areflexia imply loss of somatic and parasympathetic reflex
      activity and correlate with loss of RE. Loss of PE correlates with loss of
      perineal SSR (sympathetic denervation).

PMID- 12808707
TI  - Impact of urinary incontinence after stroke: results from a prospective
      population-based stroke register.
AB  - AIM: The purpose of this study was to investigate, in a community-based
      population, the frequency of stroke-related urinary incontinence (UI) and to
      analyse the long-term impact of UI on prognosis and institutional care. METHODS:
      Included were 752 acute stroke patients admitted consecutively during a 4-year
      period. We evaluated the UI by using the Barthel Index during the first 7 days
      and at 12-months follow-up. RESULTS: During the acute stage, the proportions of
      patients with full UI, partial UI, and no UI were 41%, 12%, and 47%, respectively
      (16%, 16%, and 68% at 12-months follow-up). A total of 45% of patients with UI at
      12 months were institutionalised compared with 5% of patients without UI. In a
      multivariate logistic regression model, age, urinary incontinence at day 7, and
      severe disability at 12 months were demonstrated to be independent factors for a
      higher frequency of institutional care 12 months after stroke. CONCLUSIONS: On
      admission in the acute stage, more than 50% of an unselected stroke population
      have UI. The proportion declines to one third of the surviving patients at 12
      months. Stroke survivors who are incontinent in the acute stage have an fourfold
      higher risk to be institutionalised after 1 year.

PMID- 12808708
TI  - Uroneurological assessment of spina bifida cystica and occulta.
AB  - AIMS: Spina bifida is a rare but well-documented congenital spinal anomaly
      comprising a cystic form, which appears in infancy, and an occult form, which
      appears in late childhood and in adulthood. Herein, we report the results of
      uroneurological assessment in patients with spina bifida cystica and occulta,
      with respect to diagnosis and management of the disorders. METHODS: We performed
      a neurological examination, urinary questionnaire, and urodynamic studies in 28
      consecutive patients with urinary symptoms, including 16 with the cystic form
      (nine male and seven female patients, ages 2 to 25 years), all of whom underwent
      neonatal surgical management, and 12 with occult form (six men and six women,
      ages 7 to 32 years) diagnosed by myelography and spinal magnetic resonance
      imaging who did not undergo surgery. RESULTS: Neurological examination revealed a
      combination of flaccid and spastic paresis, with dominant lower motoneuron signs
      in the cystic form, whereas there were dominant upper motoneuron signs in the
      occult form. Four patients with occult spina bifida presented with urinary
      symptoms as the sole initial complaint. There was no correlation between
      neurological findings and urodynamic abnormalities. Urinary incontinence and
      enuresis were common at all ages, and large post-micturition residuals and
      vesicoureteral reflux were not uncommon, particularly in the cystic form. Bladder
      abnormalities in the cystic and occult forms included detrusor hyperreflexia
      during filling in 38% and 42%, low compliance detrusor in 81% and 67%,
      supersensitivity to bethanechol in two (100%) patients with the cystic form and
      in three of four (75%) with the occult form, and impaired bladder sensation in
      25% and 8% in each form, respectively. Urethral abnormalities in cystic and
      occult forms included detrusor/sphincter dyssynergia in 50% and 27%, low Pure max
      in 56% and 17%, silent sphincter electromyographic activity in 25% and 0%, absent
      bulbocavernosus reflex in 87% and 56%, absent anal reflex in 100% and 57%,
      neurogenic motor unit potentials in one patient with cystic form studied and in
      two of three patients with occult form, respectively. CONCLUSIONS: Spina bifida
      cystica and occulta present with a wide spectrum of urodynamic abnormalities
      including upper and lower motoneuron types of bladder and urethral dysfunction.
      Careful uroneurological assessment and spinal magnetic resonance imaging are
      important for diagnosing young adult patients with spina bifida occulta because
      they may present with urinary symptoms as the sole initial complaint and have no
      other obvious neurological abnormalities.

PMID- 12808709
TI  - Loss of urinary voiding sensation due to herpes zoster.
AB  - A case of sacral herpes zoster infection in a 56-year-old man with the
      complication of loss of urinary voiding sensation is presented. He had typical
      herpes zoster eruption on the left S2 dermatome, hypalgesia of the S1-S4
      dermatomes, and absence of urinary voiding sensation. There was no other urinary
      symptom at the first medical examination. Urinary complications associated with
      herpes zoster are uncommon, but two types, acute cystitis and acute retention,
      have been recognized. No cases of loss of urinary voiding sensation due to herpes
      zoster have been reported. In this case, hypalgesia of the sacral dermatomes was
      mild compared to the marked loss of urethral sensation. This inconsistency is
      explained by the hypothesis that the number of urethral fibers is very small as
      compared to that of cutaneous fibers, therefore, urethral sensation would be more
      severely disturbed than cutaneous sensation.

PMID- 12808710
TI  - Role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder
      trigonal muscle in vitro.
AB  - AIMS: To investigate the role of beta-adrenoceptor subtypes in mediating
      relaxation of the pig bladder trigonal muscle in vitro. MATERIALS AND METHODS:
      Longitudinal strips of trigonal muscle were isolated, and the mucosa and serosa
      removed. Tissues were precontracted with KCl, and beta-adrenoceptor agonists
      (isoprenaline or salbutamol) were added cumulatively, and concentration
      relaxation curves (CRCs) were obtained. CRCs to agonists were obtained in the
      absence and presence of antagonists and antagonist affinity values were
      calculated. RESULTS: Isoprenaline (non-selective beta-agonist) relaxed with high
      potency (pEC(50) = 7.2). Propranolol antagonized CRCs to isoprenaline with a high
      affinity (apparent pK(B) = 8.8), but the Schild plot had a slope significantly (P
      < 0.01) less than unity (0.61), suggesting that responses were mediated by more
      than one beta-adrenoceptor subtype. CGP20712A (beta(1)-antagonist) antagonized
      responses to isoprenaline with a low affinity (apparent pK(B) = 5.13), indicating
      beta(1)-adrenoceptors did not participate in the response. The affinity of
      ICI118551 (beta(2)-antagonist) for antagonism of responses to isoprenaline was
      also relatively low (apparent pK(B) = 6.9), and the Schild slopes were
      significantly (P < 0.01) less than unity (0.58). SR59230A (beta(3)-antagonist)
      antagonized CRCs to isoprenaline with a relatively low affinity (apparent pK(B) =
      7.5), and with a Schild slope significantly (P < 0.01) less than unity (0.86),
      indicating that responses may be mediated by more than one beta-adrenoceptor
      subtype. In contrast to that observed with isoprenaline, the beta(2)-adrenoceptor
      selective agonist salbutamol induced relaxation with a relatively low potency
      (pEC(50) = 6.6) and with maximum responses of 80% of that to isoprenaline.
      ICI118551 competitively antagonized (Schild plot of unity) responses to
      salbutamol with a high affinity (pA2 = 8.3). CONCLUSIONS: These data suggest that
      beta-adrenoceptor mediated responses to isoprenaline of the bladder trigone are
      mediated via both the beta(2)- and beta(3)-adrenoceptor subtypes whilst responses
      to salbutamol appear to be mediated only via the beta(2)-adrenoceptor.

PMID- 12808712
TI  - The Erlangen Stroke Project.

PMID- 12808711
TI  - Ascending and descending brainstem neuronal activity during cystometry in
      decerebrate cats.
AB  - AIMS: This study was undertaken to examine the distribution of pontomedullary
      neurons related to micturition or urine storage, as well as the connections
      between the pontine micturition center (PMC), medullary neurons, and the spinal
      cord. METHODS: In decerebrate cats, extracellular recording of the rostral
      pontine and rostral medullary neurons was performed. Firing of each neuron was
      quantitated during cystometry. Connections between the PMC, medullary neurons,
      and the spinal cord (L1) were also examined electrophysiologically. RESULTS:
      Ninety-four neurons showed an increase or decrease of the firing rate during
      micturition. Units with an antidromic response to L1 stimulation and an increased
      firing rate were located in the nucleus locus coeruleus alpha (LCa; n = 8)
      corresponding to the PMC, and in the medial reticular formation (MRF) of the
      medulla (n = 14). Units showing a decreased firing rate were located in the
      nucleus reticularis pontis oralis (PoO; n = 26) and in the MRF (n = 11). The
      latencies of antidromic and orthodromic responses of the LCa units were longer
      than those of the PoO units. MRF neurons responded antidromically and/or
      orthodromically to stimulation of the PMC or L1. CONCLUSIONS: These results
      suggest that the pathway concerned with urine storage has a faster
      spinobulbospinal loop than the micturition reflex pathway and that rostral
      medullary neurons also play an important role in micturition and urine storage.
      There may be two descending pathways between the PMC and the spinal cord: both a
      direct pathway and one by means of medullary neurons.

PMID- 12808713
TI  - Intravesical ethanol 10% in saline is not an inert vehicle.

PMID- 12808715
TI  - From dust to dust: ethical and practical issues involved in the location,
      exhumation, and identification of bodies from mass graves.
AB  - There are many potential purposes served by the investigation of human remains:
      criminal fact-finding, archaeological exploration, forensic research, and others.
      This paper focuses on the identification of remains from mass graves to find
      missing persons. The primary goal of such efforts is to honor the memory of the
      dead by bringing closure to living family members, thus supporting the human
      rights of both the living and the deceased. Cultures, customs, political, and
      interpersonal specifics will vary, but that singular goal should remain the
      central guiding principle. This article presents ethical and practical issues
      resulting from efforts to locate, exhume, and identify the remains of mass
      fatalities.

PMID- 12808716
TI  - World Trade Center human identification project: experiences with individual body
      identification cases.
AB  - AIM: To present individual body identification efforts, as part of the World
      Trade Center (WTC) mass disaster identification project. METHODS: More than 500
      samples were tested by using polymerase chain reaction (PCR) amplification and
      short tandem repeat (STR) typing. The extent to which the remains were fragmented
      and affected by taphonomic factors complicated the identification project.
      Anthropologists reviewed 19,000 samples, and detected inconsistencies in 69,
      which were further split into 239 new cases and re-sampled by DNA specialists.
      RESULTS: The severity and nature of the disaster required an interdisciplinary
      effort. DNA profiling of 500 samples was successful in 75% of the cases. All
      discrepancies, which occurred between bone and tissue samples taken from the same
      body part, were resolved by re-sampling and re-testing of preferably bone tissue.
      Anthropologists detected inconsistencies in 69 cases, which were then split into
      239 new cases. Out of 125 "split" cases, 65 were excluded from their original
      case. Of these 65 cases, 37 did not match any profiles in M-FISys, probably
      because profiles were incomplete or no exemplar for the victim was available. Out
      of the 60 remains not excluded from their original case, 30 were partial profiles
      and did not reach the statistical requirement to match their original case,
      because the population frequency of the DNA profile had to be </=1 in 10(9) for
      men and </=1 in 10(8) for women. CONCLUSION: Due to transfer of soft tissue and
      other commingling of remains, DNA testing alone would have led to problems if
      only soft tissue would have been tested. This was one of the reasons that
      forensic anthropologists were needed to evaluate the consistency between all
      linked body parts. Especially in disasters with a high potential for commingling,
      the described anthropological review process should be part of the investigation.

PMID- 12808717
TI  - Development of a quality, high throughput DNA analysis procedure for skeletal
      samples to assist with the identification of victims from the World Trade Center
      attacks.
AB  - The attacks on the World Trade Center (WTC) Towers on September 11, 2001,
      represented the single largest terrorist-related mass fatality incident in the
      history of the United States. More than 2,700 individuals of varied racial and
      ethnic background lost their lives that day. Through the efforts of thousands of
      citizens, including recovery workers, medical examiners, and forensic scientists,
      the identification of approximately 1,500 victims had been accomplished through
      June 2003 (the majority of these identifications were made within the first 8-12
      months). The principal role of The Bode Technology Group (Bode) in this process
      was to develop a quality, high throughput DNA extraction and short tandem repeat
      (STR) analysis procedure for skeletal elements, and to provide STR profiles to
      the Office of the Chief Medical Examiner (OCME) in New York City to be used for
      identification of the victims. A high throughput process was developed to include
      electronic accessioning of samples, so that the numbering system of the OCME was
      maintained; rapid preparation and sampling of skeletal fragments to allow for the
      processing of more than 250 fragments per day; use of a 96-well format for sample
      extraction, DNA quantification, and STR analysis; and use of the Applied
      Biosystems 3100 and 3700 instrumentation to develop STR profiles. Given the
      highly degraded nature of the skeletal remains received by Bode, an advanced DNA
      extraction procedure was developed to increase the quantity of DNA recovery and
      reduce the co-purification of polymerase chain reaction (PCR) amplification
      inhibitors. In addition, two new STR multiplexes were developed specifically for
      this project, which reduced the amplicon size of the STR loci, and therefore,
      enhanced the ability to obtain results from the most challenged of samples. In
      all, the procedures developed allowed for the analysis of more than 1,000
      skeletal samples each week. Approximately 13,000 skeletal fragments were analyzed
      at least once, for a total of more than 18,000 analyses, and greater than 8,000
      of the skeletal samples produced STR results (65%). The percentage of successful
      results was low in relation to previous mass fatality incidents involving airline
      disasters. However, when this same process was applied to the analysis of
      skeletal remains from the American Airlines Flight 587 disaster that occurred on
      November 12, 2001, the success rate was in line with expected results (ie,
      greater than 92% of the skeletal remains produced results). This illustrated the
      quality aspects of the procedure and the degree of degradation that had occurred
      for the remains of the WTC victims. For future mass fatality incidents, the
      quality, high throughput procedures developed by Bode will allow for more rapid
      DNA analysis of victim remains, more rapid identification of victims, and thus
      more rapid return of remains to family members.

PMID- 12808718
TI  - Specific quantification of human genomes from low copy number DNA samples in
      forensic and ancient DNA studies.
AB  - We reviewed the current methodologies used for human DNA quantitation in forensic
      and ancient DNA studies, including sensitive hybridization methods based on the
      detection of nuclear alpha-satellite repetitive DNA regions or more recently
      developed fluorogenic real-time polymerase chain reaction (PCR) designs for the
      detection of both nuclear and mitochondrial DNA regions. Special emphasis has
      been put on the applicability of recently described different real-time PCR
      designs targeting different fragments of the HV1 mtDNA control region, and a
      segment of the X-Y homologous amelogenin gene. The importance of these
      quantitative assays is to ensure the consistency of low copy number DNA typing
      (STR profiling and mtDNA sequencing).

PMID- 12808719
TI  - Forensic utility of mitochondrial DNA analysis based on denaturing high
      performance liquid chromatography.
AB  - AIM: To determine the forensic utility for pairwise DNA comparisons and DNA
      mixture resolution with denaturing high-performance liquid chromatography (DHPLC)
      of human mitochondrial DNA (mtDNA). METHODS: MtDNA hypervariable regions (HV) 1
      and 2 from the mtDNA D-loop were amplified by the polymerase chain reaction and
      mixed between known and unknown sample sources. The DNA mixtures were denatured
      and reannealed, and the resultant homo- and heteroduplices were evaluated by
      temperature-modulated heteroduplex analysis by the DHPLC method. RESULTS: All 144
      pairwise comparisons of HV1 and HV2 mtDNA fragments were successfully resolved by
      the DHPLC method. Forensic proficiency test standards were successfully resolved
      and DHPLC match/non-match results agreed with sequencing results provided by the
      test providers. The DHPLC method successfully identified one questioned sample
      that was prepared by the test provider as a body fluid mixture. MtDNA amplicon
      mixtures could be separated into their constitutive components by DHPLC and
      fraction collection approaches. CONCLUSIONS: DHPLC methods provide the forensic
      scientist with a powerful tool to rapidly screen mtDNA and may result in
      standardized methods to resolve mtDNA mixtures. These advances will allow mtDNA
      analysis in cases not previously examined by current sequencing-based approaches
      and could allow more forensic case samples to be entered into the proposed mtDNA
      Combined DNA Index System (CODIS trade mark ) databank as a result of mtDNA
      mixture resolution.

PMID- 12808720
TI  - Mixed stains from sexual assault cases: autosomal or Y-chromosome short tandem
      repeats?
AB  - We analyzed forensic DNA samples from four cases of sexual assault, using the Y
      chromosome-specific human DNA markers and a panel of autosomal short tandem
      repeats (STRs). The presence of male contribution was evaluated by the analysis
      of the Amelogenin locus. A panel of tetrameric Y-STR (DYS19, DYS390, DYS391,
      DYS392, DYS385, DYS389I and II) was used in further analysis of samples,
      increasing the efficiency of the forensic genetic analyses. It was possible to
      identify a partial or full Y-profile of the rapists in different DNA mixtures
      when genetic profile could not be detected by autosomal STRs. However, in the
      case of male/male DNA mixture, only the victim's Y-profile could be obtained
      because the DNA of the offenders was present in low amounts. When the mixture
      contained different male/male proportion of DNA, only the full profile of the
      major component could be detected. In cases where male/female DNA mixed stains
      contained a sufficient amount of male DNA, the analysis of autosomal STRs was
      adequate enough to identify the full profile of the rapist. Our experience shows
      that the main advantage of the Y-STR approach is its ability to detect the male
      component in the mixed stains when the DNA of the male contributor is present
      only in a very small amount.

PMID- 12808721
TI  - Identification of human remains by immobilized sequence-specific oligonucleotide
      probe analysis of mtDNA hypervariable regions I and II.
AB  - AIM: A rapid analysis of mitochondrial DNA (mtDNA) sequences with an array of
      immobilized sequence-specific oligonucleotide (SSO) probes was tested on 18
      skeletal elements recovered from mass graves in Croatia, which could not be
      genotyped with common forensic nuclear DNA systems (PM+DQA1 and short tandem
      repeat analysis). METHODS: We used duplex polymerase chain reaction (PCR)
      amplification of the mtDNA hypervariable regions I and II (HVI and HVII) (444 bp
      and 415 bp amplicons, respectively) and subsequent linear array typing, which
      targets six polymorphic regions and two additional sites within the human mtDNA
      HVI and HVII. The remaining amplified products were subjected to direct sequence
      analysis to obtain complete sequence information for the targeted HV regions.
      RESULT: Duplex PCR amplification of the mtDNA HVI and HVII was successful in
      providing sufficient product for typing with the array of SSO probes in 14 out of
      the 18 sample extracts. We report here the sequence match of one set of remains
      with a panel of immobilized SSO probes, followed by direct sequence analysis. The
      corresponding mtDNA haplotype obtained for the bone sample and the putative
      maternal reference was unique in a database of 105 randomly selected Croatian
      individuals. CONCLUSION: Mitochondrial DNA typing with an array of immobilized
      SSO probes can be a benefit to forensic DNA analysis of mass disaster remains and
      identity testing of single and mass graves.

PMID- 12808722
TI  - Identification of forensic samples by using an infrared-based automatic DNA
      sequencer.
AB  - We have recently introduced a new protocol for analyzing all core loci of the
      Federal Bureau of Investigation's (FBI) Combined DNA Index System (CODIS) with an
      infrared (IR) automatic DNA sequencer (LI-COR 4200). The amplicons were labeled
      with forward oligonucleotide primers, covalently linked to a new infrared
      fluorescent molecule (IRDye 800). The alleles were displayed as familiar
      autoradiogram-like images with real-time detection. This protocol was employed
      for paternity testing, population studies, and identification of degraded
      forensic samples. We extensively analyzed some simulated forensic samples and
      mixed stains (blood, semen, saliva, bones, and fixed archival embedded tissues),
      comparing the results with donor samples. Sensitivity studies were also performed
      for the four multiplex systems. Our results show the efficiency, reliability, and
      accuracy of the IR system for the analysis of forensic samples. We also compared
      the efficiency of the multiplex protocol with ultraviolet (UV) technology.
      Paternity tests, undegraded DNA samples, and real forensic samples were analyzed
      with this approach based on IR technology and with UV-based automatic sequencers
      in combination with commercially-available kits. The comparability of the results
      with the widespread UV methods suggests that it is possible to exchange data
      between laboratories using the same core group of markers but different primer
      sets and detection methods.

PMID- 12808723
TI  - Different dental tissues as source of DNA for human identification in forensic
      cases.
AB  - AIM: To evaluate different dental tissues (pulp, dentin, and cement) as sources
      of DNA for forensic analysis. METHODS: A total of 20 teeth were obtained from
      unidentified bodies buried at the Central Cemetary in Bogota in 1995 and exhumed
      in 2000. The tissues from three teeth obtained after surgery were used as
      controls. The pulp cavity was exposed after cutting each tooth with a high-speed
      handpiece. The pulp was removed and processed separately from the dentin and
      cement. The dentin and cement were obtained by drilling with a high-speed
      handpiece and placed into separate tubes. DNA was extracted from mineralized
      tissues after a short decalcification step with EDTA. The DNA was quantified by
      dot-blot hybridization with D17Z1 probe, a primate- and human-specific alpha
      satellite DNA for the D17Z1 locus. Polymerase chain reaction was carried out for
      the hypervariable control region between nucleotides 29 and 408 bp (HV2 region)
      of the mitochondrial DNA, followed by gel electrophoresis to evaluate the amount
      and efficiency of the amplification. RESULTS: The pulp yielded the strongest
      amplification signals. The signals for dentin and cement were very similar
      because of the presence of cells of the periodontal ligament in the cement. The
      results of the amplification of the HV2 region of the mitochondrial DNA showed
      that dentin and cement acted as protective factors for the cells and allowed the
      conservation of the DNA. CONCLUSION: Cementoblasts and odontoblasts located
      within the cement and dentin are surrounded by the mineral matrix of the dental
      structure and thus protected from any environmental degradation forces, which
      makes them suitable sources for the DNA analysis.

PMID- 12808724
TI  - Allele and haplotype frequencies of Y-short tandem repeat loci in Turkey.
AB  - AIM: To assess the frequency distribution of six Y-chromosomal specific short
      tandem repeat (STR) polymorphisms and frequencies of haplotypes in Turkish
      population. METHODS: Blood samples were taken from 200 unrelated Turkish men from
      different regions of Turkey, who were involved in legal proceedings concerning
      paternity. The DNA was amplified and typed by use of Y-Plex 6 kit containing 6 Y
      STR markers (DYS393, DYS19, DYS389 II, DYS390, DYS391, and DYS385). Capillary
      electrophoresis was carried out on an ABI 310 Genetic Analyzer. RESULTS: Allele
      frequency profiles of the Turkish men showed no significant differences compared
      with previously published results for Swiss and German populations. The range of
      gene diversity was determined between 48.3% for DYS391 and 96.0% for DYS385. Of
      184 determined haplotypes, 170 occurred once, and the rest more than once. The
      most common haplotypes had a frequency of 1.5%. CONCLUSION: High degree of
      haplotype diversity in Turkish population makes analysis of Y-STRs a useful tool
      in forensic cases.

PMID- 12808725
TI  - An overview of DNA methods for the identification and individualization of
      marijuana.
AB  - The purpose of this review is to summarize the status of DNA-based methods for
      the identification and individualization of marijuana. In forensics, both
      identification of a substance as marijuana and the subsequent individualization
      of a sample may be desired for casework. Marijuana identification methods in the
      United States primarily include biochemical tests and, less frequently, DNA-based
      tests. Under special circumstances, DNA-based tests can be useful. For example,
      if the quantity of seized marijuana is extremely small and/or biochemical tests
      do not detect any D9-tetrahydrocannabinol (THC), DNA identification of plant
      material as Cannabis is still possible. This circumstance can arise when seeds,
      trace residue, tiny leaf fragments, or fine roots need to be analyzed. Methods
      for the individualization of marijuana include amplified fragment length
      polymorphism (AFLP), random amplified polymorphic DNA (RAPD), and short tandem
      repeat (STR) techniques that link an evidentiary sample to a source. Marijuana
      growers propagate their plants either by seed or by cloning. Seed-generated
      marijuana plants are expected to have unique DNA profiles analogous to a human
      population. Cloned marijuana plants, however, exhibit identical DNA profiles that
      allow for tracking of plant material derived from a common genetic lineage. The
      authors have validated the AFLP method for marijuana samples and are constructing
      a comparative database of marijuana seizure samples to estimate the expected
      frequency of a DNA profile match between unrelated plants. Continued development
      of DNA-based methods for plants can be useful for marijuana and other types of
      plant evidence in forensics.

PMID- 12808726
TI  - How high should paternity index be for reliable identification of war victims by
      DNA typing?
AB  - AIM: To analyze statistically and logically the significance of genetic matches
      between skeletal remains and relatives of missing persons in the process of
      identification of war victims by DNA typing. METHODS: DNA was isolated from bone
      and blood samples and short tandem repeat (STR) loci were typed by using AmpFLSTR
      Profiler, Profiler Plus, and Identifiler kits. Novel mini-haplotype analysis that
      compares matches in all three-locus combinations of alleles was developed and
      used in the analysis of inbreeding in the group of 295 unrelated individuals.
      RESULTS: While comparing 98 skeletal remains exhumed in the process of
      identification of war victims in Croatia with over 3,000 genotypes of relatives
      of missing persons, we revealed 20 cases of 14-locus matches and 4 cases of 15
      locus matches between unrelated people. We hypothesized that this unexpectedly
      high number of false matches might be a consequence of local inbreeding and
      supported this hypothesis with very low correlation between the probability of a
      genotype and the number of matching genotypes in the database (R(2) = 0.36).
      Further support for the hypothesis was obtained by the analysis of mini
      haplotypes, which revealed up to 90% overrepresentation of some mini-haplotypes.
      CONCLUSIONS: STR DNA typing is the "golden standard" of human identification, but
      evidential value of a genetic match can be easily misinterpreted. Therefore,
      careful use of statistical methods is essential for the proper evaluation of
      laboratory results. Whenever possible, multiple relatives should be analyzed and
      other evidence based on the information about time, place, and other conditions
      of disappearance, as well as anthropological and other "classical" forensic data
      should always be put together and compared before any final decision about the
      identity is made.

PMID- 12808727
TI  - Quantitative polymerase chain reaction-based assay for estimating DNA yield
      extracted from domestic cat specimens.
AB  - A quantitative polymerase chain reaction (PCR) assay has been developed for the
      quantification of genomic DNA extracted from domestic cat samples. The assay,
      which targets highly repetitive genomic short interspersed nuclear elements
      (SINE), can be performed rapidly and is highly sensitive, detecting as little as
      10 fg of feline genomic DNA. The assay was linear over a 10(6) dilution range. We
      have recently developed a short tandem repeat (STR) multiplex panel for forensic
      analysis of feline specimens. The SINE assay is an integral part of the forensic
      typing system. The sensitivity of the assay will enable forensic examiners to
      determine the likelihood of success of genotyping sample extracts with the STR
      panel without sacrificing valuable DNA necessary to perform genotyping of
      samples.

PMID- 12808728
TI  - Development of a 17-plex microsatellite polymerase chain reaction kit for
      genotyping horses.
AB  - AIM: To describe the development and performance of the new horse genotyping kit.
      METHODS: Highly discriminatory 17-Plex horse genotyping kit was designed by
      adding the fifth dye to the StockMarks kit for genotyping horses and taking
      advantage of the new instrument platforms. This was accomplished by using a new
      set of five fluorescent dyes developed by Applied Biosystems (DS-31), with four
      of the dyes used to label the forward amplification primers (6-FAM, VIC, NED, and
      PET) in each primer set. RESULTS: The new equine kit contained five extra loci
      (ASB17, LEX3, HMS1, CA425, and ASB23) in addition to the 12 original loci (VHL20,
      HTG4, AHT4, HMS7, HTG6, HMS6, HTG7, HMS3, AHT5, ASB2, HTG10, and HMS2)
      recommended by the International Society for Animal Genetics. The kit performed
      well on different instrument platforms (ABI PRISM 377, 310, and 3100 instruments)
      and across wide ranges of DNA template concentrations (1-10 ng). These 17 loci
      were combined and amplified in a single polymerase chain reaction (PCR) cycle,
      which dramatically improved the power of statistical tests for pedigree analysis
      while reducing the time and work required to perform such tests. An in-lane size
      standard labeled with the fifth dye (LIZ) provided accurate size determination
      for genotyping. CONCLUSION: The new 17-Plex horse kit, designed to improve the
      laboratory efficiency by genotyping more markers in a shorter time, has 17 primer
      sets labeled with new fluorescent dyes, which can be amplified in one PCR cycle
      and genotyped in one run on a high-throughput instruments.

PMID- 12808729
TI  - Laboratory aspects of bioterrorism-related anthrax--from identification to
      molecular subtyping to microbial forensics.
AB  - During the bioterrorism-associated anthrax investigation of 2001 in the United
      States, 11 patients were diagnosed with inhalational anthrax and 11 more with the
      cutaneous forms of the disease. Over 125,000 specimens were processed at
      laboratories of the Laboratory Response Network including those at the Centers
      for Disease Control and Prevention. Although the 2001 anthrax investigation
      initially began as a public health investigation, the forensic aspect quickly
      became a preeminent component of the investigation. Whereas a public health
      investigation aims primarily to identify the causative agent and its source, so
      that appropriate and timely control and preventative measures can be implemented,
      a forensic investigation goes further to associate the source of the causative
      agent with a specific individual or group. In addition to identification and
      molecular characterization of the causative agents, which are the crucial
      components of forensic microbiology, there are many other requirements and
      activities that need to be in place for investigators to successfully complete a
      forensic investigation. These activities include establishment of quality
      assurance/quality control criteria and regular proficiency testing for all
      laboratories where evidence is analyzed; additional and/or specialized training
      in handling and processing samples in accordance with forensic microbiology
      criteria, not only for first responders but also for laboratory and other public
      health scientists; and establishing and maintaining repositories and databases
      containing isolates of diverse temporal and geographic origins to provide a
      comparative and diverse background for investigators to identify and track the
      origin and source of such agents.

PMID- 12808730
TI  - Double incompatibility at human alpha fibrinogen and penta E loci in paternity
      testing.
AB  - We present a paternity testing case in which a double incompatibility was found
      for two short tandem repeat (STR) markers, human fibrinogen alpha (FGA) and Penta
      E. Analysis of the trio (mother, father, and daughter) included the amplification
      with a battery of 15 autosomal short tandem repeats (STR) by using a commercially
      available PowerPlex 16 System kit, and the detection with an ultraviolet
      automatic sequencer. The biological paternity was confirmed with 12 additional
      markers. Reanalysis of the trio for the same markers with different primers was
      carried out by using an infrared automated sequencer and infrared-fluorescent
      primers. High paternity index confirmed that the observed inconsistencies were
      due to a double mutation, which was confirmed by sequence analysis at FGA and
      Penta E loci. Amplification and detection results obtained by the infrared
      protocol showed consistent results with those obtained by ultraviolet-protocol
      and a commercially available kit. This has been our first case of double mutation
      at FGA and Penta E in a paternity testing. The use of our approach, based on two
      amplification and detection formats and on the sequence analysis, confirmed the
      observed meiotic paternal mutations.

PMID- 12808731
TI  - Paternity testing in case of brother-sister incest.
AB  - We performed a paternity test in a case of incest between brother and sister. DNA
      from blood samples of the alleged parents and their two children was obtained
      with Chelex DNA extraction method and quantified with Applied Biosystems
      QuantiBlot quantitation kit. Polymerase chain reaction (PCR) amplification of DNA
      samples was performed with AmpFlSTR SGM Plus PCR amplification kit and GenePrint
      PowerPlex PCR amplification kit. The amplified products were separated and
      detected by using the Perkin Elmer's ABI PRISM trade mark 310 Genetic Analyser.
      DNA and data analysis of 17 loci and Amelogenin confirmed the suspicion of
      brother-sister incest. Since both children had inherited all of the obligate
      alleles from the alleged father, we could confirm with certainty of 99.999999%
      that the oldest brother in the family was the biological father of both children.
      Calculated data showed that even in a case of brother-sister incest, paternity
      could be proved by the analysis of Amelogenin and 17 DNA loci.

PMID- 12808732
TI  - Analysis of DNA evidence recovered from epithelial cells in penile swabs.
AB  - In the rape case presented here, no semen, hair, or other biological evidence
      were left by the perpetuator at the crime scene or on the victim. The alleged
      assailant was arrested soon after the crime. A classical stain recovery technique
      using cotton swab moistened with sterile water was taken for recovering potential
      female epithelial cells and leukocytes deposited on the alleged assailant's penis
      during sexual assault. The organic method used for DNA extraction was quantified
      according to the slot-blot procedure and amplified at 9 and 15 polymorphic loci.
      Penile swab revealed a DNA profile of mixed origin. In addition to the suspect's
      DNA profile, DNA contribution from the victim was identified as a minor component
      in the mixture. Frequency of the profile resulted in a value of 5 x 10(-14) for
      the multiplex systems AmpFlSTR Plus and 2.5 x 10(-18) for the multiplex system
      PowerPlex 16, taking into account only non-overlapping alleles between the
      suspect and the victim from the minor component in the DNA mixture. Moreover,
      three additional alleles were observed at D21S11 locus by use of PowerPlex and
      STR SGM plus primers, which could not belong to the suspect. The victim's DNA
      profile showed the same three-banded genotype at this locus. The same pattern was
      detected when the victim's saliva or blood were used as reference samples. Our
      laboratory finding was consistent with the police report that the victim was a
      person with Down syndrome, a human genetic disease mainly resulting from trisomy
      (triplication) of the 21 chromosome.

PMID- 12808733
TI  - Scuba diver with a knife in his chest: homicide or suicide?
AB  - A scuba diver was found dead at the bottom of an undersea cave at 54.1 m water
      depth, with a knife protruding from his chest. Autopsy confirmed death due to
      both drowning and a penetrating knife wound. The incident was first considered a
      homicide and two suspects were arrested. Careful forensic analysis of the profile
      of the diver's last dive stored in the dive computer, dimensions of the undersea
      cave, as well as other forensic findings, showed that the case was a suicide,
      which the diver most probably committed while running out of air, in an attempt
      to avoid the agony of drowning. To the best of our knowledge, this is the first
      report on a suicide during diving.

PMID- 12808736
TI  - Prisons in the heart of the city.

PMID- 12808735
TI  - Autopsy and the quality of care.

PMID- 12808737
TI  - Cognitive ability and delinquent behavior among inner-city youth: a life-course
      analysis of main, mediating, and interaction effects.
AB  - Drawing on the emerging life-course paradigm in criminological theory, this study
      examines the relationship between cognitive ability and delinquent behavior
      within a sample of inner-city youth. The results indicate that net of statistical
      controls, cognitive ability maintains a robust inverse relationship with the
      likelihood of the onset of delinquency, the early onset of delinquency, and the
      persistence of delinquency during the 18-year period covered by the dataset.
      Furthermore, cognitive ability mediates the effect of concentrated disadvantage
      on both the onset and early onset of delinquency. Overall, the results of this
      study suggest that cognitive ability is an important criminogenic risk factor
      that has important implications for both correctional interventions and the
      continued development of structural and multilevel theories of crime.

PMID- 12808738
TI  - Police corruption and psychological testing: a strategy for preemployment
      screening.
AB  - The prediction, control, and prevention of police corruption represent pervasive
      and enduring problems. Researchers have suggested that intervention at the
      preemployment screening stage may be the best solution. However, investigators
      have acknowledged that existing assessment practices are flawed. This article
      proposes a strategy for the preemployment screening of law enforcement personnel.
      In particular, it examines the utility of the Inwald Personality Inventory and
      the Revised-NEO Personality Inventory in relation to assessing antisocial
      behavioral tendencies and conscientious personality traits, respectively, and
      argues that their combined use, appropriately administered in a testing
      situation, represents a reliable and valid predictor of good job performance. The
      article speculatively comments on this strategy for purposes of psychological
      testing, future research in the field, and law enforcement administration
      practices.

PMID- 12808739
TI  - Building bridges between the parole officer and the families of serious juvenile
      offenders: a preliminary report on a family-based parole program.
AB  - Responding to a model of juvenile offender case supervision that called for a new
      intervention paradigm to guide the work of probation and parole officers, the
      present article reports on the use of a family-based parole initiative known as
      the Growing Up FAST program. Developed in part as a tool for use within this new
      intervention paradigm, the Growing Up FAST parole program targets serious
      youthful offenders who have been released from juvenile correctional facilities
      and their families. Based on elements contained within the "what works"
      literature and the Balanced and Restorative Justice model, this program
      recognizes the central role that field staff can play in rehabilitation efforts.
      Demographic information and formative data regarding the first set of families to
      participate in this program are presented, then program limitations and lessons
      learned as part of the initial offering of this parole initiative are discussed.

PMID- 12808740
TI  - A multivariate analysis of sex offender recidivism.
AB  - Sex offender recidivism risk is a multifaceted phenomenon requiring consideration
      across multiple risk factor domains. The impact of treatment involvement and
      subsequent recidivism is given limited attention in comparison to other forensic
      mental health issues. The present analysis is a retrospective study of sex
      offenders treated at a secure facility utilizing a cognitive-behavioral program
      matched with an untreated correctional sample. Variables studied included
      demographic, criminal history, offense related, and treatment progress.
      Recidivism was assessed through arrest data. Multivariate analysis suggests that
      recidivism is significantly related to quality of treatment involvement, offender
      demographics, offense characteristics, and criminal history. Successfully treated
      offenders were significantly less likely to subsequently reoffend. Recidivists
      were also significantly younger, less likely married, had engaged in more victim
      grooming or less violent offending behavior, and had significantly more prior
      property charges. The authors discuss the clinical and policy implications of the
      interrelationship between treatment involvement and recidivism.

PMID- 12808741
TI  - Antisocial constructs in predicting institutional violence among violent
      offenders and child molesters.
AB  - This study investigated the ability of self-reported antisocial constructs to
      predict serious institutional infractions among a correctional sample of child
      molesters (n = 69) and violent offenders (n = 138). Each group had significant
      predictors, but the predictors differed between the two groups. Interpersonal
      problems accounted for significant incremental variance after age in the
      relationship with institutional violence for child molesters. With the violent
      offender group, alienation and impulse expression showed significant incremental
      variance after accounting for age. Alienation and impulse expression also added
      to age in the relationship with the function of failure over time for the most
      institutionally disruptive. Implications for institutional classification and
      clinical use in an offender population are discussed.

PMID- 12808742
TI  - Economic crime: does personality matter?
AB  - Since the publication of Edwin Sutherland's classical study, White Collar Crime,
      personality has been treated as completely irrelevant as a cause or as a
      correlating variable in studies of economic crime. This article questions that
      thesis. In an ongoing Swedish project studying economic crime in the areas of
      construction, engineering, and the music industry, 128 informants were
      interviewed regarding the personal character of the economic criminal compared to
      that of the law-abiding businessperson. Data were collected from five different
      regions in Sweden using the Big Five model, the personality model most often used
      within the field of personality research today. This article compares the results
      from the interviews with the few international studies that exist regarding
      economic crimes in these areas and common results are emphasized. It also
      presents nuanced analyses of the significance of personality in economic crime.

PMID- 12808743
TI  - Can the early implementers deliver?

PMID- 12808744
TI  - The primary care revolution.

PMID- 12808745
TI  - Understanding obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is characterised by various signs and symptoms,
      but specifically by the occurrence of repetitive episodes of partial or complete
      collapse of the upper airway, which prevents breathing. This is known as apnoea.
      Episodes of apnoea are usually accompanied by: loud snoring, excessive daytime
      sleepiness and a reduction of blood oxygen saturation. OSA is not a condition
      that develops spontaneously; rather it can best be described as a continuum of
      snoring. It is estimated to affect around four per cent of men and two per cent
      of women. The lack of awareness among the general population and physicians means
      that an estimated 80 to 90 per cent of people with OSA have not received a
      clinical diagnosis.

PMID- 12808746
TI  - What you need to know about... Down's syndrome.

PMID- 12808747
TI  - Flexible sigmoidoscopy.

PMID- 12808748
TI  - Patient group directions: training practitioners for competency.
AB  - Since the mid-1990s, three new initiatives have been introduced by the government
      to allow the prescribing of medicines by practitioners other than doctors:
      extended nurse prescribing, supplementary prescribing and patient group
      directions. Professional education and assessment is vital to ensure that these
      systems operate safely. After the implementation of patient group directions
      within a regional cancer centre, a training programme was developed,
      incorporating an assessment framework for competency development.

PMID- 12808749
TI  - Developing services for younger people with dementia.
AB  - The services available for younger people with dementia (typically between 45 and
      65 years of age) are underdeveloped. This article describes how one trust has
      addressed the problem through a 'coffee shop' project. This drop-in facility
      allows younger people with dementia and their carers to meet informally, support
      each other and access a range of services, such as counselling, medical
      information, help with benefits and legal advice.

PMID- 12808750
TI  - How I coped with ... working in a war zone. Interview by David Crouch.

PMID- 12808751
TI  - Raising the profile of the forgotten disease. Interview by Kathy Oxtoby.

PMID- 12808752
TI  - A chance to look at the bigger picture. Interview by Victoria Hoban.

PMID- 12808753
TI  - Congress presses forward with health care agenda despite international focus on
      Iraq.

PMID- 12808756
TI  - What do you think?

PMID- 12808754
TI  - Leading by example. Health plan CEOs helping to reshape the health care policy
      debate.

PMID- 12808755
TI  - A leading publication.

PMID- 12808757
TI  - AAHP on expanding access for the uninsured. Proposal offers realistic solutions.

PMID- 12808758
TI  - Let the patient's voice be heard in health care research. Interview by Lisette
      Hilton.

PMID- 12808759
TI  - Tackling a new opponent. NFL star tells those with diabetes to "check your feet".

PMID- 12808760
TI  - M-CARE: expanding care with complex case management.

PMID- 12808761
TI  - Disease management, care guidelines win physician support. Health plans provide
      tools to assist doctors.

PMID- 12808762
TI  - Managed care pharmacy: the job gets more intense.

PMID- 12808763
TI  - The next-generation health plan: building operational competence.

PMID- 12808764
TI  - Is there a captive insurance company in your future?

PMID- 12808765
TI  - Developing a computer database for registering and monitoring patients on chronic
      drug therapy to determine drug consumption: a pilot study.
AB  - OBJECTIVES: To develop a computerised database for monitoring actual drug
      consumption by a group of patients on chronic drug therapy and pilot the database
      to assess its effectiveness. SETTING: Community based in Chitungwiza, Zimbabwe.
      SUBJECTS: 434 patients with asthma, hypertension, epilepsy, Diabetes mellitus or
      multiple conditions whose medical information was entered into the database. MAIN
      OUTCOME MEASURE: Accessibility of information on the exact amount of drugs being
      utilised by patients. RESULTS: It was possible to determine the amount of drugs
      being consumed by the patients on chronic drug therapy from the database.
      Additional information on patient demographic data as well as adverse drug
      reactions could be compiled from that basic data. The database could also be used
      to follow up patients and record any changes in their treatment regimens and
      other relevant clinical information. CONCLUSION: It is feasible to create a
      database for monitoring actual drug consumption by patients on chronic drug
      therapy as a way of forecasting drug requirements accurately. Such a database has
      more advantages over the current methods used to estimate drug requirements. It
      could also be very useful as an information resource centre for nation-wide use.

PMID- 12808766
TI  - Orbital exenterations and squamous cell carcinoma of the conjunctiva at Sekuru
      Kaguvi Eye Unit, Zimbabwe.
AB  - OBJECTIVES: The aim of the audit was to determine the common orbital diseases
      necessitating orbital exenterations at Sekuru Kaguvi Hospital (SKH) between
      January and December 1999 and recommend ways of reducing the numbers of
      procedures done annually. DESIGN: Retrospective cross sectional study. SETTING:
      Department of Surgery, Parirenyatwa Hospital, University of Zimbabwe. SUBJECTS:
      23 patients who underwent orbital exenterations at SKH over a one year period.
      MAIN OUTCOME MEASURE: The nature of orbital tumours requiring orbital
      exenteration in Zimbabwe. RESULTS: A total of 23 patients underwent orbital
      exenteration during the period under review. Of the 23 patients, 13 (56.5%) had
      squamous cell carcinoma (SCCA) of the conjunctiva with orbital extensions, 69% of
      the 13 patients were females and the mean age of these patients was 37.2 years
      (interquartile range 28, 48). CONCLUSIONS: People in tropical regions, where
      there is a high risk of squamous cell carcinoma of the conjunctiva in terms of
      increased predisposition to solar radiation, high prevalence of HIV and
      inadequate eye care services, should seek medical attention as soon as they
      notice a persistent conjunctival growth. Conjunctival tumours should be widely
      excised and material sent for histology to confirm diagnosis and clarity of
      excision margins. All patients diagnosed as having SCCA of the conjunctiva should
      be closely monitored to facilitate early detection of recurrences and institute
      appropriate treatment.

PMID- 12808767
TI  - Trends in maternal mortality for the Greater Harare Maternity Unit: 1976 to 1997.
AB  - OBJECTIVE: To determine the magnitude, trends and the main causes of maternal
      death for Harare Maternity Hospital (HMH) and thereby identify potential areas
      for interventions. DESIGN: A descriptive retrospective analysis of maternal
      mortality data from the institution included in publications and recent annual
      reports. SETTING: Department of Obstetrics and Gynaecology Greater Harare
      Maternity Unit, Zimbabwe. MAIN OUTCOME MEASURES: The trends in maternal mortality
      ratios (MMR) and the relative importance of different causes of death between
      1976 and 1997. RESULTS: There was a decline in MMR between 1976 and the early
      1980s but there has been a steady increase in MMR for Harare residents from
      50/100,000 in 1988 to 224/100,000 in 1997. Sepsis has remained the leading cause
      of maternal death. There has been a significant increase in indirect deaths due
      to meningitis, tuberculosis and pneumonia where HIV infection is an underlying
      factor. Avoidable factors were identified at patient/community, local health
      facility and at the tertiary hospital. There has been a decline in the quality of
      care in recent years. CONCLUSION: Maternal mortality for HMH is unacceptably high
      and could still be rising. HIV infection has contributed to the worsening
      picture. Interventions to improve access and quality of care at all levels could
      lead to significant reduction in maternal deaths.

PMID- 12808768
TI  - Injury registration in a developing country. A study based on patients' records
      from four hospitals in Dar es Salaam, Tanzania.
AB  - BACKGROUND: A recent study conducted in some parts of Tanzania has revealed that
      injuries rank as the third major leading cause of death among the adult
      population only after tuberculosis and HIV/AIDS. Critical to any injury
      prevention activities is a reliable surveillance system. Such a system may for
      instance be based on hospital registration of injuries. OBJECTIVES: The aim of
      this study was to evaluate available hospital records for the purpose of
      describing the epidemiology of injuries among inpatients in four hospitals in Dar
      es Salaam, Tanzania. METHODS: The study utilized patients' medical records for
      the year 1998. The final sample included 1098 cases from four hospitals. Data
      handling and analysis was performed using statistical software SPSS for windows
      version 10.0. Cross tabulations with Chi-square testing for independence, t-test
      for difference between means (independent groups) and one way analysis of
      variance was used. RESULTS: The age group 21 to 30 years formed the largest
      proportion of injury-related admissions. The male to female ratio was 2.3 to 1.
      The largest categories of injuries were road traffic injuries (43.7%), violence
      and assaults (23.5%), and falls (13.8%). Burns accounted for 6.5% of the cases.
      The following variables were routinely recorded in case notes: gender (100%),
      nature of injury/principal diagnosis (99.6%), body part injured (99.4%), and age
      (96.4%). CONCLUSIONS: There is a need for improving the way injuries are recorded
      in hospitals. Hospitals' records could provide a useful tool for monitoring
      injury preventive activities in developing countries like Tanzania.

PMID- 12808769
TI  - Topical vaginal microbicides in HIV/STI prevention.

PMID- 12808770
TI  - Abortion admissions in rural Matebeleland north province.
AB  - OBJECTIVES: To describe the characteristics, clinical features and management of
      women admitted with an abortion in rural Zimbabwe. DESIGN: Cross sectional
      descriptive study. SETTING: Four government and two mission hospitals in rural
      Matebeleland North province. SUBJECTS: Hospital records of 355 consecutive women
      admitted with the diagnosis abortion from May to October 2000, and delivery
      registers covering the same six month period. MAIN OUTCOME MEASURES: Age, marital
      status, reproductive history, referral status, distance home to hospital,
      presenting symptoms, findings on examination, complications, management in
      hospital, final diagnosis, length of hospital stay. RESULTS: Abortion patients
      tended to be older and of higher parity than women who delivered in the same
      period. Fifteen percent were teenagers, 81.2% were married and 2% nullipara. Mean
      period of gestation was 11.3 weeks. About half of the women had been referred and
      74.4% lived within a 50 km radius from the hospital. Forty two percent had never
      used contraception. Of the users, 38.6% had discontinued in order to conceive and
      19.3% had fallen pregnant on the method. Thirty one percent of the women wanted
      no more children. One third of the abortion patients had a temperature above 37.6
      degrees C; 25.9% offensive vaginal discharge and 7% a haemoglobin of less than 6
      g/dl. Eighty percent were given antibiotics and 4.2% received a blood
      transfusion; 73.2% had an evacuation of the uterus for incomplete abortion, with
      a mean delay between admission and evacuation of 32.5 hours. Only 17.5% of the
      women had on record that they were given a contraceptive method on discharge.
      Mean length of hospital stay was 3.1 days. The case fatality rate was more than
      1%. An estimated 43.4% of the women had a possibly unsafe induced abortion prior
      to admission. CONCLUSION: As evidenced by the high morbidity and mortality,
      abortions are a serious public health problem in rural Matebeleland North. Taking
      into account that only a minority of the women with both unsafe and spontaneous
      abortions present to a hospital, it is imperative that the reproductive needs of
      the women who do come are addressed. No opportunity should be missed to offer
      contraceptives to a group of women whose use of contraception is lower than
      average. Clinical management of abortion patients could improve by earlier
      evacuation of the uterus in cases of incomplete abortion, use of local or no
      anaesthesia and by increased availability of suction cannulas in district level
      hospitals, which would also reduce length of hospital stay.

PMID- 12808771
TI  - Body fluid shifts in soldiers after a jogging/walking exercise in the heat:
      effects of water and electrolyte solution on rehydration.
AB  - OBJECTIVES: To examine the relationships between dehydration and body fluid
      shifts and the effects of ingesting water or oral rehydration solution or no
      fluid during and after exercise in the heat [mean (SE)] temperature, 40.5 (0.66)
      degrees C and 32 (3.7)% humidity. DESIGN: PRE and POST three hours exercise
      comparative study. SETTING: Zimbabwe National Army Wafa-Wafa Training Camp,
      Kariba, Zimbabwe. SUBJECTS: 18 male soldiers volunteered to be studied during and
      after a 20 km (three hour) jogging/walking exercise in full kit. MAIN OUTCOME
      MEASURES: Body mass, total body water, extracellular water, intracellular water,
      plasma osmolality, plasma sodium, and volume changes compared using paired t
      test. RESULTS: Total body water decreased by 4.9 (0.38) 1 (p < 0.02) in soldiers
      exercising without fluid, 1.5 (0.3) 1 (oral rehydration solution), 2.4 (0.8) 1
      (water). Extracellular water decreased by 3.6 (0.3) 1 (p < 0.05), 1.3 (0.2) 1,
      1.7 (0.3) 1, and intracellular water decreased by 1.3 (0.1) 1, 0.2 (0.01) 1, 0.7
      (0.01) 1 respectively in these groups. Plasma volume decreased by [mean (SE)] 16
      (1.4)% on no fluid, three (0.3)% on oral rehydration solution, five (0.3)% on
      water. Plasma osmolality increased significantly from 285 (1.0) to 301 (2.3)
      mosmol.kg-1 (p < 0.001) in subjects exercising without fluid and from 283 (2.0)
      to 291 (0.7) mosmol.kg-1 (p < 0.02) in subjects taking oral rehydration solution.
      No significant increases were observed when taking water only. CONCLUSIONS:
      During dehydration, total body water loss was derived from both fluid
      compartments but extracellular water contributed the most. Effective rehydration
      depends on adequate replacement of electrolytes lost from each fluid compartment.
      Water alone may not provide adequate rehydration.

PMID- 12808772
TI  - Susceptibility of Zimbabwean Streptococcus agalactiae (group B Streptococcus;
      GBS) isolates to four different antibiotics.
AB  - OBJECTIVE: To establish the susceptibility of Zimbabwean GBS strains isolated
      from hospitalised patients to four antibiotics. DESIGN: Cross sectional survey.
      SETTINGS: Four regions of Zimbabwe (Bindura, Bulawayo, Harare, and Masvingo).
      SUBJECTS: 113 GBS isolates from hospitalised patients in Bindura, Bulawayo,
      Harare and Masvingo, of whom most were suffering from infectious diseases. MAIN
      OUTCOME MEASURES: All isolates were tested for their susceptibility to
      clindamycin, erythromycin, penicillin and tetracycline. RESULTS: All isolates
      were 100% sensitive to clindamycin, 98% to penicillin, 86% to erythromycin; 2% of
      the isolates showed intermediate susceptibility to penicillin and 100% showed
      resistance to tetracycline. CONCLUSION: Penicillin is still the antibiotic of
      choice for treatment of GBS infections and for intrapartum chemoprophylaxis in
      Zimbabwe. For patients who are allergic to penicillin, clindamycin will be the
      drug of choice for both treatment and/or chemoprophylactic use in Zimbabwe.

PMID- 12808773
TI  - Choledochal cyst associated with HIV (human immunodeficiency virus) disease.

PMID- 12808774
TI  - Current considerations in the management of the elderly hypertensive patient.

PMID- 12808775
TI  - A critical incident reporting system in anaesthesia.
AB  - OBJECTIVE: To audit the recently established Critical Incident Reporting System
      in the Department of Anaesthesia and Critical Care Medicine, University of
      Zimbabwe Medical School. The system was set up with the purpose of improving the
      quality of care delivered by the department. DESIGN: Cross sectional study. A
      critical incident was defined as 'any adverse and reversible event in theatre,
      during or immediately after surgery that if it persisted without correction would
      cause harm to the patient'. The anaesthetic or recovery room staff filled a
      critical incident form anonymously. Data was collected from critical incident
      reporting forms for analysis. SETTING: The anaesthetic service in the two
      teaching hospitals of Harare Central and Parirenyatwa General Hospitals.
      SUBJECTS: Between May and October 2000, 62 completed critical incident forms were
      collected. MAIN OUTCOME MEASURES: The nature of the incident and the monitoring
      used were recorded, the cause was classified as human, equipment or monitoring
      failure and the outcome for each patient reported. There was no formal system for
      reminding staff to fill in their critical incident forms. RESULTS: A total of
      14,165 operations were performed over the reporting period: 62 critical incident
      forms were collected, reporting 130 incidents, giving a rate of 0.92%
      (130/14,165). Of these, 42 patients were emergencies and 20 elective. The
      incidents were hypotension, hypoxia, bradycardia, ECG changes, aspiration,
      laryngospasm, high spinal, and cardiac arrest. Monitoring present on patients who
      had critical incidents was: capnography 57%, oxymetry 90% and ECG 100%. Other
      monitors are not reported. Human error contributed in 32/62 of patients and
      equipment failure in 31/62 of patients. Patient outcome showed 15% died, 23% were
      unplanned admissions to HDU while 62% were discharged to the ward with little or
      no adverse outcome. CONCLUSION: Despite some under reporting, the critical
      incident rate was within the range reported in the literature. Supervision of
      juniors is not adequate, especially on call. The stress under which everyone has
      to work includes poor morale, drug shortages, poor equipment and power cuts with
      no backup generator. Despite this, the challenge for senior personnel is to
      improve quality of care. In other countries similar audits have led to change of
      practice and improvement in the safety features of the service provided by the
      hospital and staff.

PMID- 12808776
TI  - Effectiveness and safety of high dose oxytocin for augmentation of labour in
      nulliparous women.
AB  - OBJECTIVE: To compare high and low starting dose of oxytocin infusion for
      effectiveness and safety in augmentation of labour in nulliparous women. DESIGN:
      An open randomised controlled clinical trial. SETTING: Harare Maternity Hospital,
      Zimbabwe. SUBJECTS: 258 nulliparous women, with spontaneous onset of labour, who
      required augmentation. MAIN OUTCOMES MEASURES: Duration of augmentation, mode of
      delivery, maternal and neonatal complications. INTERVENTIONS: Women were randomly
      allocated to either low dose (starting at 4 mIU/minute) or high dose (starting at
      10 mIU/minute) oxytocin group. RESULTS: Of the 258 women enrolled, 133 were
      randomized to the low and 125 to the high starting oxytocin dose groups. The
      groups were comparable for maternal and gestational age. There was no difference
      in mean cervical dilatation before augmentation of labour; six cm in both groups
      (p = 0.167). The mean augmentation to delivery interval was shorter in the high
      dose group, 218 versus 326 minutes (p < 0.001). There was no difference in the
      mode of delivery and fetal outcome in terms of birthweight, five minute Apgar
      score, admission to neonatal unit and perinatal death. CONCLUSION: A high
      starting dose of oxytocin infusion is as safe but more effective for augmentation
      of labour in nulliparous women, compared to a low starting dose.

PMID- 12808777
TI  - Mercury poisoning: prevalence, knowledge and frequency of gold panning and doing
      retort among alluvial gold panners in Chiweshe and Tafuna communal lands in
      Zimbabwe.
AB  - OBJECTIVES: To estimate the prevalence of mercury poisoning, to estimate the
      knowledge level that mercury can be a poison, and to establish the frequency of
      gold panning and doing retorts. DESIGN: Cross sectional study. SETTING: Chiweshe
      and Tafuna communal lands. SUBJECTS: Gold panners. MAIN OUTCOME MEASURE: Mercury
      levels in blood and urine. RESULTS: Totals of 23 respondents from Chiweshe and 43
      respondents from Tafuna were recruited. Four out of 43 respondents in Tafuna and
      seven out of 23 respondents in Chiweshe had levels of mercury greater than 0.05
      mg/L in blood (p = 0.040). Out of 43 respondents in Tafuna, four (9.3%) had
      levels of mercury of more than 0.01 mg/L in urine. Totals of 18 out of 37 and
      seven out of 22 respondents from Tafuna and Chiweshe, respectively, did not know
      that mercury could be a poison. Altogether, 35 (56.5%) out of 62 respondents were
      full time gold panners. Significantly more respondents in Chiweshe (14/19) than
      in Tafuna (8/29) did less than four retorts per month (p = 0.005). Respondents
      who did four or more retorts per month were 3.21 (95% CI 1.06 to 9.72) times more
      likely to have had raised levels of mercury in their blood compared with persons
      who did less than four retorts per month. CONCLUSION: Mercury poisoning among
      gold panners in Chiweshe and Tafuna communal lands is of public health
      importance. Panners should be educated on the possibilities of mercury being a
      poison. A low cost and safe technology to separating mercury from the amalgam
      should be introduced to the panners.

PMID- 12808779
TI  - Rationalizing the cost of anaesthesia in Zimbabwe: a proposal.

PMID- 12808778
TI  - Asymptomatic salmonellosis and drug susceptibility in the Buea District,
      Cameroon.
AB  - OBJECTIVES: The objectives were to investigate the prevalence of asymptomatic
      Salmonella infections in Buea and determine the antibiotic susceptibility pattern
      of isolates cultured from carriers. DESIGN: This was a descriptive study.
      Subjects were randomly selected from the community. Stool samples or rectal swabs
      were collected after consent to participate in the study. These samples were
      cultured on standard media. Salmonella species isolated were tested for
      antibiotic sensitivity by the agar diffusion method. SETTING: The study was
      carried out in three localities of the Buea district of Cameroon namely Molyko,
      Great Soppo and Bolifamba. SUBJECTS: 156 participants aged three months to 47
      years old who were not suffering from fever, gastroenteritis or other signs and
      symptoms were recruited. INTERVENTION: Carriers of Salmonella were referred to
      the medical doctor of the university of Buea Health Unit. MAIN OUTCOME MEASURES:
      Asymptomatic carriers could eventually form the basis of an effective
      epidemiological surveillance system in developing rational strategies to control
      Salmonella infections. RESULTS: Salmonella species were isolated in 62 (39.7%)
      subjects with the following distribution: eight (5.1%) S. typhi, 19 (12.2%) S.
      paratyphi and 35 (22.4%) S. typhimurium. No significant difference was observed
      between those who were infected with the different Salmonella species (p > 0.05).
      The most effective antibiotic was ofloxacin while resistance to chloramphenicol
      was remarkable. S. typhimurium showed the highest resistance to all antibiotics
      tested. CONCLUSION: The population of Buea is at risk of acquiring Salmonella
      infections from asymptomatic individuals. An effective surveillance system to
      detect carriers and properly treat them is highly recommended.

PMID- 12808780
TI  - An investigation of symptomatic malaria parasitaemia and anaemia in nursery and
      primary school children in Buea District Cameroon.
AB  - OBJECTIVES: To investigate the prevalence of asymptomatic malaria parasitaemia
      and anemia in nursery and primary school children and correlate parasite density
      with haemoglobin levels. DESIGN: Cross sectional study. SETTING: Samples were
      collected from children attending the Saint Theresa's bilingual school and the
      Government Primary school, Buea, South West Province, Cameroon. SUBJECTS: 297
      nursery and primary school children two to 11 years old selected based on
      parental consent. MAIN OUTOME MEASURES: Relationship between asymptomatic malaria
      and anaemia. RESULTS: The prevalence of asymptomatic malaria in children was
      30.3%. Parasite prevalence and density was independent of age and sex (p > 0.05).
      The mean haemoglobin level for parasitaemic children was 11.9 g/dl (+/- SD1.1)
      compared with 12.1 g/dl (+/- 1.2) for non-parasitaemic children. The difference
      was not significant (t = 1.918, p > 0.05). Anaemia when present was mild. No
      correlation was found between malaria parasite density and haemoglobin levels (r
      = -0.065; p > 0.05). CONCLUSION: Asymptomatic malaria was accompanied by low
      grade parasitaemia, which did not seem to have a significant effect on
      haemoglobin levels.

PMID- 12808781
TI  - Nutrition knowledge and food choice among black students in South Africa.
AB  - OBJECTIVES: To investigate the relationship between nutrition knowledge and
      dietary behaviour, and to assess the perceived influences on food selection among
      Black students in South Africa. DESIGN: Cross sectional study. SETTING:
      University of the North and two semi-urban Secondary Schools. SUBJECTS: 213
      second year social science university students, 104 (48.2%) male and 112 (51.9%)
      female, and 199 Grade 11 secondary school students, 67 male (32.7%) and 132
      female (66.3%). MAIN OUTCOME MEASURES: A General Nutrition Knowledge
      Questionnaire and a Food Choice Questionnaire. RESULTS: Generally, students
      seemed to have below average nutrition knowledge levels. University students had
      significantly more nutrition knowledge than secondary school students. Dietary
      recommendations were associated with source of nutrients and diet-disease
      relationships, and sources of nutrients were associated with diet-disease
      relationships. Choosing everyday foods was not associated with dietary
      recommendations, source of nutrients, and diet-disease relationships. Among both
      university and secondary school students the three highest food choice factors
      included health, sensory appeal and mood. CONCLUSION: Below average nutrition
      knowledge levels were found. Choosing everyday food seemed to be not associated
      with nutrition knowledge, and food choice was not only influenced by health but
      also sensory appeal and mood.

PMID- 12808782
TI  - The mandibular angles of dry adult human mandibles from north eastern arid zone
      of Nigeria.
AB  - OBJECTIVES: To study and document the mandibular angle of Nigerians from the
      north eastern arid zone, and investigate its role as an anthropological parameter
      for racial and or population groups differential diagnosis, its utilization in
      laryngoscopy and for successful inferior alveolar nerve anesthesia. DESIGN: A
      cross sectional study. SETTING: Department of Anatomy, College of Medical
      Sciences, University of Maiduguri, Maiduguri, Borno State, Nigeria. SUBJECTS: 60
      dry adult mandibles from Nigerians who lived in Maiduguri (Borno State Capital)
      and its environ until their death. MAIN OUTCOME MEASURES: Measurements of the
      right and left mandibular angles, length and height of the mandibles and the
      comparison of the mean angle with that of other racial and or population groups.
      RESULTS: The mean mandibular angle (118.75 +/- 0.395 i.e. mean +/- SEM) was
      smaller than that of other African populations but was wider than that of the
      Neanderthals and similar to that of the Chinese and Peruvians. The mandible had a
      shorter ramus, slightly longer length resulting in a smaller angle than that of
      the Zimbabwean mandible. Highly significant differences occurred between the mean
      angle of the Nigerian mandible and those of other African population groups (p <
      0.0001) except the mandibular angle of Natal Nguni and Cape Nguni populations
      from South Africa. There was no mutual dependence and no significant departure
      from linearity between the mean angle, length and height. CONCLUSION: The
      mandibular angle in conjunction with other anthropological parameters may be
      useful anthropological tools in racial and or population diagnosis. The
      configuration of the mandible of Nigerians from the northeast arid zone may
      predispose them to difficult laryngoscopy and/or intubation.

PMID- 12808783
TI  - Specialisation patterns of medical graduates, University of Malawi College of
      Medicine, Blantyre.
AB  - OBJECTIVE: To describe specialization patterns of medical graduates of the
      University of Malawi College of Medicine. DESIGN: Cross sectional study.
      SUBJECTS: Medical graduates of the University of Malawi College of Medicine.
      SETTING: University of Malawi College of Medicine. MAIN OUTCOME MEASURES:
      Speciality choices, sources of funding for training, employer at time of graduate
      studies and country where specialist training obtained. RESULTS: Between 1991 and
      2000, 60 (35.5%) of the 169 graduates of the College of Medicine of the
      University of Malawi have obtained or are in specialist training, 38/60 (63.3%)
      with training institutions either in the United States or the United Kingdom, 10
      (16.7%) had gone to South Africa, 8% Kenya, 5% to the Republic of China (Taiwan)
      and 3.3% to Uganda. Other countries are; Uganda, Australia and Finland. The
      preferred specialties were; Public Health 17 (28.8%), Internal Medicine 12 (20%)
      and Paediatrics 10 (16.7%). Most of the funding was provided by
      agencies/institutions in the USA and UK. At the time of their training
      fellowship, 33 (55%) of the candidates were employed by the College of Medicine,
      24 (40%) by the public service and the rest, three (5%) by other institutions.
      CONCLUSIONS: Most Malawian medical graduates are obtaining their specialty
      training overseas funded mostly by institutions/agencies in the UK and USA. There
      is need to explore ways on how training could be provided regionally. Malawi and
      her neighbours must develop post graduate speciality training locally and
      regionally.

PMID- 12808784
TI  - Bony anomalies of the craniocervical junction.
AB  - A review of the literature on bony anomalies of the craniovertebral junction was
      carried out with emphasis on anomalous manifestations associated with the
      occipital bone, atlas and axis vertebrae. A summary of the evolution and normal
      development of the above bony structures and the embryological structures
      contributing to the bony anomalies is presented. In addition the diagnostic
      measurements used for the diagnosis of the bony anomalies of the craniocervical
      junction and their clinical presentation were summarised. This review was
      prepared with the aim of providing reference material for neurosurgeons and
      radiologists.

PMID- 12808785
TI  - Parthenium hysterophorus allergy.

PMID- 12808786
TI  - A toolkit for trainer appraisal and development.
AB  - All GPs are required to undergo formal revalidation and appraisal. Revalidation
      and re-accreditation assess past performance with a view to licensing future
      activity. GP trainers have additional responsibilities for delivering high
      quality education to tomorrow's doctors beyond those of a GP. In order to fulfill
      this role trainers are required to attend re-accreditation courses by their local
      educational establishments and will have different needs to those of their doctor
      role. Course organizers have responsibilities that include the organisation and
      assurance of quality of the training provided by their scheme. Although there are
      no absolute definitions of good quality teaching, it is widely accepted that
      proxy measures for both consulting and teaching are important and definable. In
      the case of teaching registrars, these include provision for welcoming, inducting
      and informing new registrars, assessing their needs, and providing a climate in
      which they can flourish, as well as actually teaching them. This toolkit explores
      a system of appraisal designed to help trainers achieve these tasks efficiently,
      using structured feedback from registrars as well as the trainers' own reports as
      a basis for discussion during an appraisal interview. It contains some hints for
      interviewers and comments on the likely issues to emerge, as well as the basic
      tools needed to conduct the process. The toolkit can be adapted for local use. It
      has been well received by the trainers, and refined in the light of their
      feedback.

PMID- 12808787
TI  - Severe acute respiratory syndrome.

PMID- 12808788
TI  - Lymphatic filariasis.

PMID- 12808789
TI  - [Infections--allergies--cancers. Attacks on the lung].

PMID- 12808790
TI  - [Progress in interventional bronchology. Valves for treating pulmonary
      emphysema].

PMID- 12808791
TI  - [Bacterial-fungal cocktail from aerosol generators. Indoor waterfall lung].

PMID- 12808792
TI  - [Early detection of bronchial carcinoma. How effective is screening of risk
      patients?].

PMID- 12808793
TI  - [Tormenting muscle pains refractory to all treatment attempts. Finally cortisone
      therapy leads to right track].

PMID- 12808794
TI  - [Chronic inflammatory bowel diseases. Dermatoses and joint pain can be the
      initial symptoms].

PMID- 12808795
TI  - [Trauma of the cervical spine. Only medicine winds up in a skid].

PMID- 12808796
TI  - [Trauma of the cervical spine. Only medicine winds up in a skid].

PMID- 12808797
TI  - [Trauma of the cervical spine. Only medicine winds up in a skid].

PMID- 12808798
TI  - [Trauma of the cervical spine. Only medicine winds up in a skid].

PMID- 12808799
TI  - [Cor bovis and metallic gold in heart failure? A positive list for shamans!].

PMID- 12808800
TI  - [Drug therapy and adjuvant therapy in heart failure. Exercise training--more
      effective than digitalis?].
AB  - Physical training is known to have a favorable effect on the extracardiac causes
      of intolerance of exertion associated with cardiac insufficiency. Randomized
      studies have shown an improvement in the oxidative capacity of the skeletal
      muscles, to an attenuation of chronic inflammation, correction of endothelial
      dysfunction, and to normalization of the frequently pathological ventilation
      under effort. The result is an increase in the maximum oxygen uptake--depending
      on the study--of between 15% and 29% (average 2 ml/kg min). An old worry that
      physical training might lead to a worsening of hemodynamics was not confirmed. As
      a result of the positive effect of training on the neurohumoral system and the
      peripheral endothelial function the resistance of peripheral vessels was lowered
      and the burden on the left ventricle reduced. The results of initial long-term
      observational studies also reveal a reduction in mortality.

PMID- 12808801
TI  - [Anticoagulation--control of heart rate--cardioversion. Therpeutic algorithm in
      ventricular tachycardia].
AB  - The first therapeutic step in the emergency situation absolute tachyarrhythmia in
      underlying atrial fibrillation is the immediate initiation of anticoagulation
      treatment with heparin, followed by control of the ventricular frequency.
      Cardioversion promises success when: atrial fibrillation < 48 hours,
      transesophageal echocardiography excludes a thrombus, > 3 weeks effective
      anticoagulation, left ventricle < 50 mm, and atrial fibrillation not longer than
      one year. In the emergency situation electric cardioversion is to be preferred to
      drug-induced cardioversion. If the pumping function is reduced, amiodarone is a
      safe agent for rhythm stabilization. Care must be exercised with verapamil,
      digitalis and adenosine in irregular broad QRS complex tachycardia and suspected
      WPW syndrome.

PMID- 12808802
TI  - [Early detection of myocardial infarct risk with cardio-CT. Can coronary calcium
      calculation prevention sudden cardiac death?].
AB  - The measurement of the calcium score with the cardio-CT is an option for
      determination of the individually elevated risk of a heart attack. In contrast to
      cardiac catheterization, the calcium score does not assess the coronary lumen,
      but rather the coronary vessel wall. Therefore, cardiac catheterization and
      calcium scoring are not competing but complementary tests: cardiac
      catheterization is performed to prove coronary stenoses, i.e. in patients with
      angina pectoris, while cardio-CT is used for the prognostic evaluation in
      asymptomatic patients. Cardio-CT should not be used to determine if cardiac
      catheterization should be performed. Also, in patients with angina pectoris,
      known coronary artery disease, s/p myocardial infarction or high absolute
      coronary risk, there is no indication for calcium scoring with cardio-CT. The
      prevailing indication for cardio-CT is detection of patients at high risk of a
      heart attack defined as > 2% annually. The recently presented St. Francis Heart
      Study has shown that calcium scoring provides a significantly higher prognostic
      value than the traditional Framingham score.

PMID- 12808803
TI  - [Differential alopecia areata diagnosis. Looking for clues im sparse scalp hair].

PMID- 12808804
TI  - [Schoenlein-Henoch immune vasculitis. The varigated picture of purpura].

PMID- 12808805
TI  - [Drooping upper eyelid. In the evening it is especially severe].

PMID- 12808806
TI  - [Basedown disease, thyroid gland autonomy, nodular goiter. When is radiotherapy
      indicated?].
AB  - Treatment options for benign diseases of the thyroid include medication,
      radioiodine therapy and surgery. Patients with hyperthyroidism initially receive
      antithyroid drugs, with further treatment determined by the relapse risk. In the
      case of Graves' disease this is determined by a number of risk factors, including
      the volume of the thyroid gland or the presence of endocrinal ophthalmopathy. In
      such cases with a high relapse risk, radioiodine therapy is the recommended first
      line treatment. Further indications--if surgery is not necessary--are autonomous
      goiter, recurrent (autonomous) goiter and latent hyperthyroidism. A single
      radioiodine treatment suffices to control the situation in more than 90% of the
      cases, and the goiter clearly diminishes in size. Radiation-induced malignancies
      or malformations have not been seen, but iodine treatment is contraindicated in
      pregnancy. In view of the short hospital stay of only four to five days, and the
      ready availability of treatment units, the authors consider radioiodine therapy a
      suitable first-line option in patients with Graves' hyperthyroidism.

PMID- 12808807
TI  - [How does disease management work? A manual for diabetes DMP should clarify the
      issue].

PMID- 12808808
TI  - [Reading it twice--then you are experts (interview by Susanne Pickl)].

PMID- 12808809
TI  - [Backache--specific or nonspecific? With a 5-minute test for differential
      diagnosis].

PMID- 12808810
TI  - [Dangerous deficits in management of hypertensive diabetic patients. A kidney
      check is far from standard procedure].

PMID- 12808811
TI  - [Proper diagnosis--preventing complications. Inflamed pancreas].

PMID- 12808812
TI  - [New drugs for cancer, diabetes, dpression. Therapy a la genetic code].

PMID- 12808813
TI  - [Arm wrestling, hypnosis or patches? Colleagues--tipps for smoking cessation
      (interview by Dr. Judith Neumaier)].

PMID- 12808815
TI  - [Specific immunotherapy in desensitization of allergic patients. Oral
      administration instead of injections? (interview by Andrea Warpakowski)].

PMID- 12808814
TI  - [Reality in general practice. Capabilities required of the general practitioner].

PMID- 12808816
TI  - [Illness caused by work pressure. Occupational stresses are not appreciated
      enough as etiologies of illness].

PMID- 12808817
TI  - [Time pressure, inadequate wages, fear of unemployment. When work causes
      illness].
AB  - Changing demands made by the workplace may be associated with psychomental and
      socioemotional stresses. Underlying reasons involve work organization and
      specific work content, as also social relationships at the workplace, the
      remuneration situation, and the risks related to the occupational biography of
      the individual. Changes in the workplace-related risks necessitate further
      investigations into the work and performance process relevant to the individual
      case.

PMID- 12808818
TI  - [Finding the reasons for "workplace phobia". Sick leave can cause damage].
AB  - Anxiety engendered by the workplace leads to an inability to work and earn one's
      living. The term workplace phobia is applied when anxiety leads to avoidance of
      the workplace. As in the case of school phobia, a range of differential diagnoses
      may be involved, requiring careful clarification. Such may include post-traumatic
      stress disease, posttraumatic embitterment, social phobia, personality disorders,
      depression and organic brain disease. The treatment of workplace-related phobia
      differs from that of other phobias because of the peculiarities of the workplace.
      Simply giving the patient sick leave may do more harm than good, and as such
      needs to be carefully weighed up.

PMID- 12808819
TI  - [Mobbing, discrimination, sexual harrassment. How can work site personnel
      counseling facilities help?].

PMID- 12808820
TI  - [The so-called preventive house call. Forestalling nursing home admission].
AB  - In view of the increasing numbers of elderly citizens in the general population,
      there is a need to ensure that they receive medical care within a setting of
      independence preservation and, wherever possible, within the domestic
      environment. Preventive house calls can contribute greatly to efforts made to
      achieve this aim. The implementation of this effective instrument should be in
      the hands of a team of specially trained family doctors, nurses and geriatric
      care-providers. During a house call, a multidimensional geriatric assessment
      covering such aspects as mobility, nutritional status, somatosensory status, and
      domestic and social environment, should be made. Of essential importance is the
      long-term care of the geriatric patient, which can be realized by the family
      doctor via repeated house calls. Current cost/benefit analyses clearly favor
      anchoring the preventive house calls in the public health service.

PMID- 12808821
TI  - [Improving early detection. A simple screening test for asthma and COPD].

PMID- 12808822
TI  - [Lumbar back pain. Consensus concept for initial diagnosis in general practice].

PMID- 12808823
TI  - [Therapy of hypertension. Pulse pressure must also be reduced].

PMID- 12808824
TI  - [Adverse effect-free analgesia. New COX-2 inhibitor is even more selective].

PMID- 12808825
TI  - [Hear failure. Indications for diuretic therapy in general practice].

PMID- 12808826
TI  - [Leukotriene antagonist added in asthma therapy. Loophole in anti-inflammatory
      therapy closed].

PMID- 12808827
TI  - Recent expose of cruelty towards older people prompts call for human rights
      commissioner.

PMID- 12808828
TI  - City challenges.

PMID- 12808829
TI  - Nurse consultants and the care of older people: developing new roles.

PMID- 12808830
TI  - Dementia and personhood: implications for advance directives.

PMID- 12808831
TI  - Continence and older people: the importance of functional assessment.
AB  - Continence problems among older people are debilitating, embarrassing and
      uncomfortable but, despite widely held views to the contrary, with sound
      assessment their effects can be minimised.

PMID- 12808832
TI  - Assessing blood results in older people: cardiac enzymes and biochemistry.

PMID- 12808833
TI  - Playing with the service.

PMID- 12808834
TI  - My country. Interview by Daloni Carlisle.

PMID- 12808836
TI  - Safer surgeries.

PMID- 12808835
TI  - Early intervention. Interview by Mary Hampshire.

PMID- 12808837
TI  - Measure your dreams.

PMID- 12808838
TI  - Do-it-yourself health.

PMID- 12808839
TI  - Gene testing and disability.

PMID- 12808840
TI  - The reflective patient: intrapersonal care.
AB  - AIM: To consider the relevance and potential role of patient reflection in their
      overall healthcare experience. METHOD: In-depth, unstructured, qualitative
      interviews were conducted with 19 patients due to have elective orthopaedic
      surgery. A longitudinal study design was used, covering the period from a few
      weeks before to approximately three months after surgery. Forty five interviews
      were conducted in total. RESULTS: The degree to which participants expressed
      evidence of reflection and the nature of their reflections varied. Much
      reflection focused on remaining unknowns and lingering queries. Participants
      seemed to be trying to work towards an acceptable interpretation of their
      experiences. This interpretation then fed into their experience of, and responses
      to, their care. CONCLUSION: Intrapersonal care is suggested as a way of
      conceptualizing the patient's process of reflection. This complements
      interpersonal care given by nurses. Intrapersonal care must be well supported to
      realise its potential therapeutic effect.

PMID- 12808841
TI  - Post-operative pain management in day surgery.
AB  - BACKGROUND: The author carried out a literature review of post-operative pain
      management in day surgery units. CONCLUSION: Based on this review, the article
      makes recommendations for: pre-operative information for patients about their
      proposed surgery and strategies for pain relief during their stay; a recovery
      protocol for the administration of intravenous opioids of choice, in titrated
      doses, by appropriately qualified nurses; and a protocol for the administration
      of oral analgesia by nurses, from a prescribed list, for patients in pain on the
      ward.

PMID- 12808842
TI  - Atrial fibrillation: Part 2.
AB  - In the second part of this article, the author examines common causes and
      consequences of atrial fibrillation (AF). The author also discusses some of the
      investigations required to assess patients with this condition, the clinical
      features of AF and the various treatment strategies available.

PMID- 12808844
TI  - Management of risk: whose business is it?

PMID- 12808843
TI  - General prescribing principles. Improving practice.
AB  - There is a lot of information available for nurses to help monitor and develop
      prescribing practice. The most important of these include: Prescribing Analysis
      and CosT reports National Institute for Clinical Excellence National service
      frameworks PRODIGY Pharmaceutical information Local prescribing committees
      Colleagues Yourself

PMID- 12808845
TI  - Our language should show respect for older people.

PMID- 12808846
TI  - Hand hygiene is a nursing issue.

PMID- 12808848
TI  - ME and children.

PMID- 12808847
TI  - Single checking of controlled drugs.

PMID- 12808849
TI  - More voices bring greater choices.

PMID- 12808850
TI  - Treatment decisions at the end of life.

PMID- 12808851
TI  - SARS: current advice and information for would-be travellers.

PMID- 12808852
TI  - Blood-borne viral STIs.

PMID- 12808853
TI  - A communication protocol to help patients with sensory impairment.
AB  - Patients with sight, hearing and speech impairment are entitled in law to equal
      access to health care according to the Disabilities Discrimination Act. More and
      more patients experience these problems as the population grows older. This paper
      reports on how a group of staff in one trust helped set up a protocol to ensure
      that this group's communication needs are tackled.

PMID- 12808854
TI  - Cellular pathophysiology. Part 1: Changes following tissue injury.
AB  - This paper provides a comprehensive review of the pathophysiological responses to
      an insult to the body. It is generally not the extent of the initial injury but
      rather the less understood, incredibly complex, diffuse cellular complications
      that cause irreversible damage to cells, tissues and organs. The effects of this
      can last for months or years after the initial insult.

PMID- 12808855
TI  - New topical treatments in the management of atopic eczema.
AB  - Atopic eczema is a common condition that is not caused by any single factor. The
      nurse has an important role in educating patients about the condition, teaching
      them how to control their symptoms and providing follow-up support for treatment.
      Nurses in both primary and secondary care are also likely to be responsible for
      counselling patients and their families.

PMID- 12808856
TI  - Adverse health-care events: Part 2. Incident reporting systems.
AB  - This paper, the second in a series of four on adverse health events, outlines the
      process for reporting, investigating and learning from clinical incidents. It
      outlines the nursing contribution and nurses' responsibility with regards to
      effective clinical risk management in order to achieve a major cornerstone of
      clinical governance--making the NHS safer for patients.

PMID- 12808857
TI  - Poor systems and staffing problems led to poor patient outcomes.
AB  - The office of the Health Service Ombudsman regularly publishes reports of
      complaints investigated by its assessors. The cases presented here relate to
      failures of nursing care: some of the problems were found to be the result of
      inadequate staffing and training, others were due to poor documentation, lack of
      staff accountability and inadequate organisation.

PMID- 12808858
TI  - The Five-a-Day campaign: how nurses can promote healthier diets.
AB  - Nurses in both primary and secondary care have a crucial role in encouraging
      patients to eat more healthily; in particular, by promoting the benefits of
      eating at least five portions of fruit and vegetables--or just 400 g--a day. This
      has been shown to reduce the risk of coronary heart disease and the incidence of
      the more common cancers prevalent in the UK.

PMID- 12808859
TI  - Taking action on urology.

PMID- 12808860
TI  - An evaluation of a nurse-led cystoscopy surveillance service.
AB  - The findings of a regional audit found that Salford had a high incidence of
      superficial bladder cancer. It was felt that the needs of the patient population
      could best be served by introducing a nurse-led cystoscopy service. This paper
      reports on the findings of a postal survey to evaluate the appropriateness and
      quality of care offered by the new service.

PMID- 12808861
TI  - Intermittent self-catheterisation for managing urinary problems.
AB  - Intermittent self-catheterisation is mainly practiced by patients with urinary
      incontinence or voiding difficulties. In one trust it was offered as an
      alternative to urology patients who fail their trial without catheter. A review
      of this practice investigated frequency of patient ISC, concordance with
      treatment and views on care.

PMID- 12808862
TI  - The role of the modern matron in a urology department.
AB  - The introduction of modern matrons--strong clinical leaders--is part of
      Government policy for the health service. In October 2001 the post of urology
      matron was set up in one London trust. This paper discusses her experience of the
      job, examines the key objectives for the matron role and describes the challenges
      faced.

PMID- 12808863
TI  - Safeguarding children: 5. Listening as part of the child-protection process.
AB  - Adults cannot always assume that they know what is best for children and young
      people. Without listening to young clients, it is not possible to meet their
      needs. Part five of this series considers how health-care professionals can
      become good listeners to and advocates of those under their care, and looks
      forward to the forthcoming National Service Framework for children.

PMID- 12808864
TI  - How a pyramid helps to unravel the stages of nursing assessment.
AB  - Teaching nurses at one college's nursing and midwifery department how to assess
      patients and clients has been made easier with the help of a visual pyramid
      developed by one lecturer. The model highlights the need to distinguish between
      holistic, physical and specialist/specific assessment.

PMID- 12808865
TI  - Turning the tables: when a cancer patient contributes to staff training.

PMID- 12808866
TI  - End of the line.

PMID- 12808867
TI  - Fall from grace.

PMID- 12808868
TI  - Money on the mind.

PMID- 12808869
TI  - The HSJ interview: Andrew Dillon. The NICE guy. Interview by Lyn Whitfield.

PMID- 12808870
TI  - Practice managers. Value added facts.
AB  - South Manchester PCT set up a one-day-a-month course to aid the professional
      development of practice managers. This was the first time practice managers had
      been engaged through a tailored programme. GPs now encourage their practice
      managers to attend the course having seen the benefits.

PMID- 12808871
TI  - Mental health. Pay attention.
AB  - Research into user involvement groups in mental health was conducted to make them
      more effective. Responses revealed frustration about a lack of real input, use of
      volunteers, lack of payment and burn-out of activists. The responses also
      revealed a widespread feeling of 'influence without power'.

PMID- 12808873
TI  - Law. Knowledge is power.

PMID- 12808872
TI  - Data briefing. The euro.

PMID- 12808874
TI  - HSJ people. Judgement day.

PMID- 12808875
TI  - Appetite suppressants: problems and pitfalls of drug discovery.

PMID- 12808876
TI  - Prospects for obesity treatment: MCH receptor antagonists.
AB  - The convergence of the orphan G protein-coupled receptor SLC-1 with its
      orexigenic neuropeptide ligand melanin-concentrating hormone (MCH) in 1999
      stimulated considerable research activity aimed at characterizing the role of
      this receptor system in the regulation of body weight. A solid body of genetic
      and pharmacological evidence now supports a role for MCH in the modulation of
      food intake and energy expenditure. High-throughput screening efforts have led to
      the identification of small molecule MCH receptor antagonists with diverse
      structural features and drug-like properties. In vivo results with two of these
      antagonists indicate efficacy in several animal models of body weight regulation
      and feeding behavior. Based on these preclinical findings, it is likely that
      reports from clinical studies of MCH antagonists will soon be forthcoming.

PMID- 12808877
TI  - The impact of statin treatment on diabetic patients.
AB  - Retrospective analysis of secondary prevention trials indicates that 3-hydroxy-3
      methyglutaryl coenzyme A reductase inhibitors (statins) reduce the risk of
      recurrent coronary heart disease events in individuals with diabetes. Diabetic
      individuals may receive greater benefit from statin treatment than non-diabetic
      individuals, because of a higher absolute risk. Available data are limited,
      although several randomized trials of primary prevention with diabetic patients
      are ongoing. The low-density lipoprotein cholesterol goal is now considered to be
      < 100 mg/dl for individuals with diabetes. Pleiotropic effects of statins may be
      involved in anti-atherogenic or other actions of statin.

PMID- 12808879
TI  - Thiazolidinediones in diabetes: current status and future outlook.
AB  - Thiazolidinediones have recently emerged as promising antidiabetic drugs. Unlike
      other oral antidiabetic drugs, thiazolidinediones function to ameliorate insulin
      resistance, a primary factor for the development of type 2 diabetes.
      Thiazolidinediones are ligands of the nuclear receptor, peroxisome proliferator
      activated receptor-gamma, and their antidiabetic effects appear to be mediated by
      activation of this receptor. The two currently marketed thiazolidinediones,
      rosiglitazone and pioglitazone, display similar efficacies in their glucose
      lowering activities, but interestingly display slightly different clinical and
      side effect profiles. Understanding the molecular basis for these differences
      will help in the development of next generation thiazolidinediones that are more
      efficacious and safer for the treatment of type 2 diabetes.

PMID- 12808878
TI  - Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2
      diabetes.
AB  - New therapies for the long-term treatment of type 2 diabetes are needed to
      ameliorate declining pancreatic beta-cell function. Ideally, these therapies
      should lower fasting and post-prandial blood glucose, produce no hypoglycemia or
      weight gain, cause no other limiting side effects, and reduce cardiovascular
      complications. Exenatide (synthetic exendin-4) is a potential therapeutic which
      may fulfill these criteria. Dose-ranging studies have identified an optimal dose
      of 0.05 to 0.2 microgram/kg administered subcutaneously twice daily.
      Pharmacokinetic data support a pivotal study design which mitigates the transient
      nausea observed in early studies by including a dose initiation period of 1 month
      at 5 micrograms twice daily, followed by maintenance therapy at 10 micrograms
      twice daily. Ongoing studies suggest exenatide improves glycemic control through
      a combination of mechanisms discussed in this review.

PMID- 12808880
TI  - Dipeptidyl peptidase IV inhibitors for the treatment of impaired glucose
      tolerance and type 2 diabetes.
AB  - Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L
      cells in the small intestine in response to the ingestion of nutrients and
      enhances the glucose-dependent secretion of insulin from pancreatic beta-cells.
      In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide
      decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell
      function. Hormone action is rapidly terminated by the N-terminal cleavage of GLP
      1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). The short in
      vivo half-life of GLP-1 (< 3 min) poses challenges to the development of
      exogenous GLP-1-based therapy. The inhibition of endogenous GLP-1 degradation by
      reducing DPPIV activity is an alternative strategy for improving the incretin
      action of GLP-1 in vivo. This review summarizes recent advances in the design of
      potent and selective small molecule inhibitors of DPPIV and the potential
      challenges to the development of DPPIV inhibitors for the treatment of impaired
      glucose tolerance and type 2 diabetes.

PMID- 12808881
TI  - Pharmacological regulation of hepatic glucose production.
AB  - The discovery of antidiabetic agents that inhibit hepatic glucose production is a
      popular and potentially fruitful research area for the pharmaceutical research
      community. Metformin, a marketed agent with this mechanism of action, is widely
      used for the treatment of type 2 diabetes, however, more efficacious agents are
      sought. A number of promising proteins are being targeted for modulation by new
      compounds, including the glucagon receptor, glycogen phosphorylase,
      glucocorticoid receptor, 11 beta-hydroxysteroid dehydrogenase-1, fructose-1,6
      bisphosphatase, carnitine palmitoyltransferase-1, glycogen synthase kinase-3,
      glucose-6-phosphate T1 translocase and the A2B receptor. Compounds designed to
      work against these targets are at the early clinical or preclinical phase of
      study. Glucagon receptor antagonists, glycogen phosphorylase inhibitors, 11 beta
      hydroxysteroid dehydrogenase-1 inhibitors, carnitine palmitoyltransferase-1
      inhibitors and fructose-1,6-bisphosphatase inhibitors are, or have been,
      clinically evaluated. Preclinical studies against the other targets have yielded
      compounds that demonstrate efficacy in diabetic animal models and clinical
      activity will continue.

PMID- 12808882
TI  - Regulation of insulin receptor kinase activity by endosomal processes: possible
      areas for therapeutic intervention.
AB  - The insulin receptor kinase (IRK) is activated following insulin binding and is
      rapidly internalized into endosomes (ENs) from which signaling occurs. Four
      endosomal processes limit the intensity and duration of intracellular signal
      transduction: (i) insulin degradation by an endosomal acidic insulinase,
      cathepsin D, which removes the ligand leading to receptor deactivation; (ii) IRK
      dephosphorylation by an associated protein tyrosine phosphatase abrogates its
      activated state; (iii) acidification of ENs changes IRK conformation reducing its
      affinity for ligand and inactivating its kinase; and (iv) trafficking within ENs
      can sequester activated IRK from signal transduction elements. Each process
      presents an opportunity for new potential therapeutic approaches.

PMID- 12808883
TI  - Novel treatment options for overlapping yet distinct erectile dysfunction and
      andropause syndromes.
AB  - The Food & Drug Administration has recently approved, or is in the process of
      approving newer drugs such as the phosphodiesterase inhibitors and apomorphine to
      treat men's health issues including erectile dysfunction. Increasing age results
      in a gradual hypogonadal state in men, for which different novel delivery systems
      of androgens are currently offered for the symptomatic patient. As such, many men
      are presenting to healthcare practitioners for the first time. The age of
      presentation for erectile dysfunction and andropause often overlaps, typically in
      the fifties and beyond, therefore, it makes sense to screen for erectile
      dysfunction in andropause patients and vice versa. Erectile dysfunction is
      usually a harbinger for other illnesses, such as coronary heart disease and
      depression. The hypogonadal state, likewise, could be a harbinger for other ill
      health states in men, including obesity, depression, osteoporosis and possibly
      memory loss. While the newer treatments for erectile dysfunction and andropause
      are distinctly different and targeted at symptom relief, the presentation of the
      patient with erectile dysfunction or andropause offers an excellent opportunity
      for screening for other health states and health education strategies.

PMID- 12808884
TI  - Hormone replacement therapy and health protection.
AB  - Menopause is potentially a cause of concern and hormone-related diseases. Hormone
      replacement therapy (HRT) is considered to be an effective treatment strategy to
      relieve menopausal symptoms and prevent related diseases, however, knowledge on
      HRT and its benefits and risks is still evolving. For many climacteric women, HRT
      is the ideal choice to treat symptoms, prevent diseases and improve quality-of
      life, while for others it can cause concerns and problems. Thus, the appropriate
      role of HRT has still to be fully defined. An individualized, patient-tailored
      approach to HRT, based on the current evidence of risk factors for hormone
      related diseases and treatments, is essential to maximize the benefits and
      minimize the risks.

PMID- 12808885
TI  - MK-767. Kyorin/Banyu/Merck.
AB  - MK-767 (KRP-297, L-410198) is a peroxisome proliferator-activated receptor (PPAR)
      alpha and PPAR gamma agonist under development by Banyu, Kyorin and Merck for the
      potential treatment of diabetes. The compound is currently undergoing phase III
      trials in the US and phase I trials in Japan.

PMID- 12808886
TI  - Insulin detemir. Novo Nordisk.
AB  - Insulin detemir (NN-304) is a soluble, long-acting insulin analog being developed
      by Novo Nordisk for the potential treatment of type 1 and 2 diabetes. As of
      February 2003, Novo Nordisk was expecting both US and EU approval in the first
      half of 2004. In December 2002, Novo Nordisk submitted an NDA to the FDA and an
      NDS to the Canadian Biologics & Genetics Therapeutic Directorate for the approval
      of insulin detemir for the treatment of diabetes mellitus.

PMID- 12808887
TI  - NN-414. Novo Nordisk.
AB  - Novo Nordisk is developing NN-414, an orally active beta-cell-selective regulator
      of insulin release, for the potential treatment of type 1 and type 2 diabetes.
      Phase 1 efficacy trials were underway by November 2000; these trials were ongoing
      in February 2002 and had been concluded by February 2003.

PMID- 12808888
TI  - Exenatide. Amylin/Eli Lilly.
AB  - Amylin Pharmaceuticals Inc and Eli Lilly & Co are co-developing exenatide (AC
      2993; synthetic exendin-4), a 39-amino acid, glucagon-like peptide-1 agonist
      derived from the venom of the Gila monster lizard (Heloderma suspectum) as a
      potential injectable treatment for type 2 diabetes. The first phase III trial
      (exenatide as a monotherapy) was initiated in December 2001. In January 2002 the
      second phase III trial, of exenatide in conjunction with sulfonylureas, was
      initiated and in March 2002, Amylin initiated the third phase III trial, of
      exenatide in combination with metformin and sulfonylureas.

PMID- 12808889
TI  - SomatoKine. Insmed.
AB  - SomatoKine, a recombinant fusion of insulin-like growth factor-1 and its binding
      protein, BP-3, is being developed by Insmed (formerly Celtrix Pharmaceuticals)
      for the potential treatment of growth hormone insensitivity syndrome (GHIS), and
      as a potential injectable insulin sensitizer for the management of type 1 and
      type 2 diabetes in patients who are less sensitive to insulin therapy. By July
      2002, the FDA had granted SomatoKine Orphan Drug status for the treatment of
      GHIS. Also at this time, a phase II trial in children suffering from GHIS was
      initiated. In September 2002, Insmed expected to initiate a further clinical
      trial in GHIS in early 2003, and planned to continue phase II development in type
      1 and type 2 diabetes.

PMID- 12808890
TI  - Miglustat. Oxford GlycoSciences/Actelion.
AB  - Oxford GlycoSciences and Actelion have developed and launched miglustat (OGT-918;
      Vevesca; Zavesca) for the treatment of type 1 Gaucher disease. Miglustat is an
      orally administered small-molecule glucosylceramide glucosyltransferase inhibitor
      licensed from Searle, and it is also in development for the treatment of other
      glycolipid storage disorders such as Tay-Sachs, Fabry and Niemann-Pick type C
      diseases. In November 2002, miglustat received EU approval for the treatment of
      Gaucher disease and was launched in the UK in March 2003 by Actelion. At this
      time, additional EU launches were expected over the next few months.

PMID- 12808891
TI  - [Realities in management of water electrolyte imbalance--special reference to
      fluid infusion therapy].

PMID- 12808893
TI  - [Pathophysiological study on water electrolyte imbalance--special reference to
      sodium metabolism disorders].

PMID- 12808892
TI  - [Pathophysiological study on water electrolyte imbalance--special reference to
      body-water metabolism disorder].

PMID- 12808894
TI  - [Pathophysiological study on water electrolyte imbalance--special reference to
      potassium metabolism disorders].

PMID- 12808895
TI  - [Pathophysiological study on water electrolyte imbalance--special reference to
      calcium-phosphorus metabolism disorders].

PMID- 12808896
TI  - [Pathophysiological study on water electrolyte imbalance--special reference to
      acid-base imbalance].

PMID- 12808897
TI  - [Management and diagnosis of water electrolyte imbalance manifested as
      dehydration and oliguria].

PMID- 12808898
TI  - [Management and diagnosis of water electrolyte imbalance due to kidney diseases].

PMID- 12808899
TI  - [Water electrolyte balancing in management of patients with heart failure].

PMID- 12808900
TI  - [Water electrolyte balancing in management of patients with respiratory failure].

PMID- 12808901
TI  - [Water electrolyte balancing in management of patients with liver failure].

PMID- 12808902
TI  - [Management of water electrolyte imbalance associated with diabetes mellitus].

PMID- 12808904
TI  - [Management of water electrolyte imbalance in aged patients].

PMID- 12808903
TI  - [Management of water electrolyte imbalance in infants and children].

PMID- 12808905
TI  - [Realities in the use and application of total parenteral nutrition].

PMID- 12808906
TI  - [Role of ion channels of kidney in water-electrolyte metabolism].

PMID- 12808907
TI  - [Water electrolyte imbalance associated with kidney tubular transport inborn
      error].

PMID- 12808909
TI  - [Clinical physicians' views on water electrolyte imbalance (discussion)].

PMID- 12808908
TI  - [Renal tubular acidosis].

PMID- 12808910
TI  - [Cytomegalovirus colitis in a patient with severe refractory ulcerative colitis].

PMID- 12808911
TI  - [De novo acute lymphocytic leukemia with t(14;18) complicated by tumor lysis
      syndrome].

PMID- 12808912
TI  - [Systemic lupus erythematosus with multifocal posterior pigment epitheliopathy].

PMID- 12808913
TI  - [Focal autoimmune pancreatitis which discovered for formation of a large
      pancreatic pseudocyst].

PMID- 12808914
TI  - [Case of systemic mastocytosis with hemophagocytic syndrome].

PMID- 12808915
TI  - [Therapeutic angiogenesis for patients with critical limb ischemia using
      autologous bone marrow cell transplantation].

PMID- 12808916
TI  - [Molecular targeting therapy for chronic myelogenous leukemia].

PMID- 12808917
TI  - [Transcription factors and diabetes mellitus].

PMID- 12808919
TI  - [Classification of angina pectoris].

PMID- 12808918
TI  - [Angina--concept, definition, and progress of clinical research].

PMID- 12808920
TI  - [Pathophysiology of myocardial ischemia and anginal chest pain].

PMID- 12808921
TI  - [Symptoms of angina pectoris].

PMID- 12808922
TI  - [Angina pectoris: symptomatology and differential diagnosis].

PMID- 12808923
TI  - [Angiographic diagnosis of ischemic heart disease].

PMID- 12808924
TI  - [Electrocardiographic diagnosis of angina pectoris].

PMID- 12808925
TI  - [Ultrasound diagnosis of angina pectoris].

PMID- 12808926
TI  - [Clinical significance of myocardial perfusion imaging for patients with angina
      pectoris].

PMID- 12808927
TI  - [Assessment of myocardial ischemia by stress perfusion scintigraphy].

PMID- 12808928
TI  - [Left ventricular function in angina pectoris].

PMID- 12808929
TI  - [Factors influencing the progress and prognosis of angina pectoris].

PMID- 12808931
TI  - [Medical treatment in patients with angina pectoris].

PMID- 12808930
TI  - [The type of angina pectoris and the selection of the treatment].

PMID- 12808933
TI  - [Coronary revascularization: the indication, selection of operative methods and
      long-term results].

PMID- 12808932
TI  - [Percutaneous coronary angioplasty for the treatment of angina pectoris:
      indication, selection of procedures, and initial and late results].

PMID- 12808934
TI  - [Coronary spasm and coronary atherosclerosis in early stage].

PMID- 12808935
TI  - [Circadian variation of basal total vascular tone in patients with vasospastic
      angina pectoris--pathogenesis and treatment].

PMID- 12808936
TI  - [Diagnosis of coronary artery spasm].

PMID- 12808937
TI  - [Vasospastic angina and serious ventricular arrhythmia].

PMID- 12808938
TI  - [Clinical characteristics of multivessel coronary artery spasm].

PMID- 12808939
TI  - [Clinical and experimental evidences regarding the relations of coronary
      vasospasm to progression of organic coronary stenosis and acute myocardial
      infarction].

PMID- 12808940
TI  - [Transient left ventricular dysfunction (stunned myocardium) following coronary
      artery spasm].

PMID- 12808941
TI  - [Treatment and prognosis of vasospastic angina].

PMID- 12808942
TI  - [Definition and the classification of unstable angina].

PMID- 12808943
TI  - [Pathophysiology and management for unstable angina based on the responsiveness
      to drug treatment].

PMID- 12808944
TI  - [Myocardial scintigraphy for the detection of unstable angina pectoris].

PMID- 12808945
TI  - [Acute phase CAG and clinical type in patients with unstable angina].

PMID- 12808946
TI  - [Coronary angioscopy and unstable angina].

PMID- 12808947
TI  - [Clinical value of biochemical markers in patients with unstable angina].

PMID- 12808948
TI  - [Blood coagulation/fibrinolytic system in unstable angina].

PMID- 12808949
TI  - [Percutaneous coronary intervention in unstable angina].

PMID- 12808950
TI  - [Surgical indication for unstable angina].

PMID- 12808951
TI  - [Refractory unstable angina].

PMID- 12808952
TI  - [Stable effort angina--definition and classification].

PMID- 12808953
TI  - [Pathophysiology of stable effort angina].

PMID- 12808954
TI  - [Diagnosis of stable effort angina pectoris].

PMID- 12808955
TI  - [Treatment and prognosis of stable effort angina].

PMID- 12808956
TI  - [Acute coronary syndrome--an overview of its pathophysiology].

PMID- 12808957
TI  - [Coronary plaque formation and rupture].

PMID- 12808958
TI  - [Pathogenesis of coronary spasm].

PMID- 12808959
TI  - [Detection and management of vulnerable plaque].

PMID- 12808960
TI  - [Thrombus formation and platelet].

PMID- 12808961
TI  - [Thrombus formation and tissue factor].

PMID- 12808962
TI  - [Acute coronary syndrome].

PMID- 12808964
TI  - [Classifications of myocardial infarction].

PMID- 12808963
TI  - [Medical treatment of acute coronary syndromes].

PMID- 12808965
TI  - [The pathogenesis of myocardial infarction and risk factors].

PMID- 12808966
TI  - [Secondary prevention of myocardial infarction].

PMID- 12808967
TI  - [Distribution of coronary stenoses and occlusions in ischemic heart disease].

PMID- 12808968
TI  - [An interpretation of electrocardiographic wave forms in myocardial infarction
      and its clinical significance].

PMID- 12808969
TI  - [Mechanisms of ventricular arrhythmias in myocardial infarction].

PMID- 12808970
TI  - [Non-Q-wave infarction and Q-wave infarction].

PMID- 12808971
TI  - [Clinical manifestation, pathophysiology and treatment of right ventricular
      infarction].

PMID- 12808972
TI  - [A clinical and pathological study of atrial infarction].

PMID- 12808973
TI  - [Progress in management of acute myocardial infarction].

PMID- 12808974
TI  - [Body surface potential mapping].

PMID- 12808975
TI  - [Two-dimensional echocardiographic assessment of myocardial infarct size and
      viability and the prediction of clinical course in acute myocardial infarction].

PMID- 12808976
TI  - [Assessment of myocardial viability with MR imaging].

PMID- 12808977
TI  - [Evaluation of necrosis and viability of myocardium after acute myocardial
      infarction, and risk stratification by nuclear method].

PMID- 12808978
TI  - [Assessment of myocardial infarct size by cardiac markers].

PMID- 12808979
TI  - [Diagnosis and risk stratification of non Q wave myocardial infarction].

PMID- 12808980
TI  - [Prehospital care for acute myocardial infarction].

PMID- 12808981
TI  - [Cardiac life support for acute coronary syndrome].

PMID- 12808982
TI  - [Intensive care for acute myocardial infarction (coronary care unit: CCU)].

PMID- 12808983
TI  - [Relationship between the location and size of myocardial infarction and pump
      failure--predictors of cardiogenic shock associated with acute myocardial
      infarction].

PMID- 12808984
TI  - [Killip and Forrester classifications for patients with acute myocardial
      infarction].

PMID- 12808985
TI  - [Pharmacologic treatment of heart failure in patients with acute myocardial
      infarction].

PMID- 12808986
TI  - [Progress and practice of treatment for pump failure].

PMID- 12808987
TI  - [Progress in ventricular assist systems (VAS) and treatment of pump failure].

PMID- 12808988
TI  - [Present status of heart transplantation for ischemic heart disease].

PMID- 12808989
TI  - [Incidence and prognostic significance of arrhythmias after the myocardial
      infarction].

PMID- 12808990
TI  - [Prognostic value of arrhythmias in acute myocardial infarction].

PMID- 12808991
TI  - [Late potential and prediction of malignant ventricular arrhythmias].

PMID- 12808992
TI  - [The treatment of periinfarction arrhythmias].

PMID- 12808993
TI  - [Catheter ablation for the treatment of arrhythmia associated with myocardial
      infarction].

PMID- 12808994
TI  - [Emergency surgery for the complications of myocardial infarction].

PMID- 12808995
TI  - [Strategies and selection of reperfusion therapy for acute myocardial
      infarction].

PMID- 12808996
TI  - [PTCA for acute myocardial infarction--classification, adaptation, and effect].

PMID- 12808997
TI  - [Reperfusion therapy and ischemic preconditioning].

PMID- 12808998
TI  - [Diagnosis and treatment for reperfusion injury].

PMID- 12808999
TI  - [Prevention of acute coronary occlusion after reperfusion therapy--application of
      antithrombotic drugs].

PMID- 12809000
TI  - [Efficiency and limitation of late myocardial reperfusion therapy].

PMID- 12809001
TI  - [Advantages of reperfusion therapy in AMI].

PMID- 12809002
TI  - [Strategy for preventing or treating 'no reflow' phenomenon].

PMID- 12809003
TI  - [Emergency CABG: indication and current status].

PMID- 12809004
TI  - [Clinical pathways for early rehabilitation program in patients with acute
      myocardial infarction].

PMID- 12809005
TI  - [Nonatherosclerotic coronary artery disease].

PMID- 12809006
TI  - [Silent myocardial ischemia: clinical concept, classification, and diagnostic
      criteria].

PMID- 12809007
TI  - [Perception of anginal pain in myocardial ischemia and mechanisms of silent
      myocardial ischemia].

PMID- 12809008
TI  - [Pathophysiology of asymptomatic myocardial ischemia].

PMID- 12809009
TI  - [Clinical features, frequency and prognosis of asymptomatic myocardial ischemia].

PMID- 12809010
TI  - [Silent myocardial ischemia in elderly patients: Clinical feature and prognosis].

PMID- 12809011
TI  - [Characteristics and prognosis of silent myocardial ischemia in diabetic
      patients].

PMID- 12809012
TI  - [Medical treatment for silent myocardial ischemia].

PMID- 12809013
TI  - [Interventional therapy for silent ischemia].

PMID- 12809014
TI  - [Pre-infarction and post-infarction angina--examination from autopsied hearts].

PMID- 12809015
TI  - [Pathophysiological mechanisms of early post-infarction angina (relationship with
      PCI)].

PMID- 12809016
TI  - [Short-term and long-term prognosis of postinfarction angina in the reperfusion
      era].

PMID- 12809017
TI  - [Long-term prognosis of myocardial infarction].

PMID- 12809018
TI  - [Prevention and treatment of the severe complications of myocardial infarction in
      chronic phase].

PMID- 12809019
TI  - [Coronary flow reserve of infarct region in patients with previous myocardial
      infarction].

PMID- 12809020
TI  - [Clinical significance of treadmill stress testing in old myocardial infarction;
      correlation with the severity of coronary artery stenosis].

PMID- 12809021
TI  - [The rehabilitation program of a myocardial infarction in chronic stage].

PMID- 12809022
TI  - [Exercise therapy in phase 3 cardiac rehabilitation for patients with MI].

PMID- 12809023
TI  - [Secondary prevention of myocardial infarction].

PMID- 12809024
TI  - [Long-term prognosis of old myocardial infarction treated by medication, PTCA and
      CABG].

PMID- 12809025
TI  - [Myocardial infarction in the aged].

PMID- 12809026
TI  - [Myocardial infarction in women].

PMID- 12809027
TI  - [Acute myocardial infarction in young adults].

PMID- 12809028
TI  - [The differentiation between tako-tsubo-like left ventricular dysfunction and
      acute myocardial infarction].

PMID- 12809029
TI  - [Pathophysiology of ischemic myocardium].

PMID- 12809030
TI  - [Hemodynamics and adaptive mechanisms of the ischemic heart].

PMID- 12809031
TI  - [Left ventricular remodeling after acute myocardial infarction].

PMID- 12809032
TI  - [Chronic heart failure and ischemic heart disease].

PMID- 12809033
TI  - [Ischemic cardiomyopathy].

PMID- 12809034
TI  - [Assessment of myocardial viability and angioplasty in ischemic cardiomyopathy].

PMID- 12809035
TI  - [Electrophysiological characteristics of ischemic myocardium].

PMID- 12809036
TI  - [Sudden cardiac death in ischemic heart disease].

PMID- 12809037
TI  - [Prediction of ventricular tachyarrhythmias in patients with old myocardial
      infarction: assessment of ventricular vulnerability by body surface mapping and
      signal-averaged electrocardiogram].

PMID- 12809038
TI  - [Infection and ischemic heart disease].

PMID- 12809039
TI  - [Endothelial function and ischemic heart disease--approach from vascular
      endocrinology].

PMID- 12809040
TI  - [Ischemic heart disease and cytokines].

PMID- 12809041
TI  - [Ischemic heart disease and oxidative stress].

PMID- 12809043
TI  - [Adenosine and ischemic heart disease].

PMID- 12809042
TI  - [Tissue renin-angiotensin system and ischemic heart diseases].

PMID- 12809044
TI  - [Endothelin and ischemic heart diseases].

PMID- 12809045
TI  - [The role of nitric oxide in ischemic heart disease].

PMID- 12809046
TI  - [Chymase in ischemic cardiovascular diseases].

PMID- 12809047
TI  - [ADMA (asymmetric dimethyl arginine) and coronary artery disease].

PMID- 12809049
TI  - [Chronic renal failure and ischemic heart disease].

PMID- 12809048
TI  - [Rho-kinase inhibitors for ischemic heart disease].

PMID- 12809050
TI  - [Diabetes mellitus and ischemic heart diseases].

PMID- 12809051
TI  - [Cerebrovascular diseases and ischemic heart diseases].

PMID- 12809052
TI  - [Ischemic heart disease and heart transplantation].

PMID- 12809053
TI  - [Cardiac rehabilitation in ischemic heart disease--along with a new guideline on
      exercise therapy in heart disease].

PMID- 12809054
TI  - [Autonomic nervous system and ischemic heart disease].

PMID- 12809055
TI  - [Sildenafil and ischemic heart disease].

PMID- 12809056
TI  - [Coronary heart disease and hormone replacement therapy].

PMID- 12809057
TI  - [Guidelines for the prevention and treatment of coronary artery disease].

PMID- 12809058
TI  - [Clinical trials in coronary disease].

PMID- 12809059
TI  - [Syndrome X and microvascular angina--studying process, concept, definition and
      pathogenesis].

PMID- 12809060
TI  - [Diagnostic criteria for syndrome X].

PMID- 12809061
TI  - [Ultrastructures of small vessels and cardiomyocytes in patients with micro
      vascular angina].

PMID- 12809062
TI  - [Pathogenesis and pathophysiology of syndrome X].

PMID- 12809063
TI  - [Therapeutic strategy and prognosis in patients with syndrome X].

PMID- 12809064
TI  - [Coronary atherectomy].

PMID- 12809065
TI  - [Coronary stent].

PMID- 12809066
TI  - [New generation of antiarrhythmic drugs in coronary heart disease].

PMID- 12809067
TI  - [Donor-cell-derived acute leukemias after allogeneic bone marrow
      transplantation].
AB  - The authors survey the clinical, immunophenotypic, cytogenetic, molecular genetic
      spectrum and pathogenetic mechanisms of donor cell derived acute leukemias after
      allogeneic bone marrow transplantation. The main aspects for detection of donor
      cell origin and the available therapeutic approaches are discussed through
      demonstration of one documented patient and data of the literature. Several
      hypotheses are summarized which try to explain how donor cell leukemia might
      arise including occult leukemia in the donor cells, transfer of oncogene from
      host to donor cells and the role of impaired immune surveillance. Investigation
      of donor cell leukemia cases might bring closer to understand the pathogenesis of
      leukemia serving as a model for studying the leukemiagenesis in vivo.

PMID- 12809068
TI  - [Experience in first-line chemotherapy with paclitaxel for the treatment of
      ovarian carcinomas].
AB  - OBJECTIVE: The purpose of this study was to investigate the possible benefit of
      the paclitaxel based combined chemotherapy introduced as an "up front"
      chemotherapy in Hungary for the treatment of ovary cancer. METHODS: Data of four
      Hungarian Ovary Cancer Treatment Center was collected, evaluated and presented
      here as a preliminary retrospective study. Data of 67 patients was included into
      the investigation who underwent laparatomy followed with paclitaxel/carboplatin
      or paclitaxel/cisplatin combined chemotherapy between 1st of July 1999 and 31st
      of December 2000. The paclitaxel was administered as 135 mg/m2 i.v. infusion for
      3 hours. The main attention was pay on the response rate and the side effect
      occurred during the administration of the anticancer drugs. RESULTS: 34 out of 67
      patients underwent optimal surgery, and 33 out of 67 had got suboptimal procedure
      only. The chemotherapy was started at the 7th postoperative day. 430 cycles of
      chemotherapy was evaluated. The overall response rate (RR) at the end of the
      treatment was 76.1% (CR 68.65%. PR 7.46%). At the end of the follow-up there was
      41 patients free of disease (61.19%), 12 patients alive with residual disease
      (17.91%), 10 patients (14.9%) died of disease, and there was 4 (6%) patients
      lost. The overall survival (OS) during the follow up period was 16.82 months. In
      the suboptimally operated group, 36.3% of the patients (12/33) underwent second
      laparotomy after the 3rd cycle of chemotherapy. Optimal operation was done in 8
      out of this 12 patients and all of optimally operated patients remained free of
      disease at the and of the follow up. Three treatment out of 67 was interrupted
      because of major side effect, and 13 patients needed supportive treatment. Eleven
      blood transfusions was performed during the chemotherapy and erythropoetin (EPO)
      was administered in two patients. CONCLUSIONS: The outcome of patients during of
      follow up period was better in the optimally operated group. There was 2 death
      compared to 8 in suboptimally operated group, the progression free survival (PFS)
      was longer (8 vs. 6.54 months), and so was the OS (17.11 vs. 16.54 months). More
      disease free patients was registered at the end of follow-up in the optimally
      operated group (29 vs. 12). The haematological side effect was also more frequent
      in the suboptimally operated group (12 vs 1). The data suggest that the quality
      of initial surgical procedure remains the main prognostic factor even if
      paclitaxel based combine chemotherapy is administered. On the other hand due to
      the paclitaxel based chemotherapy seems to be a promising "up front" treatment in
      patients with ovary cancer with few major side effect generally, and quite a lot
      haematological side effect in the suboptimally operated group only.

PMID- 12809069
TI  - [Adjuvant therapy with parenteral piracetam in alcohol withdrawal delirium].
AB  - The author reports his results of parenteral piracetam treatment in 193 patients
      admitted to the Psychiatric Department of Semmelweis Hospital with alcohol
      withdrawal delirium. Alcohol withdrawal delirium is a complex metabolic disorder,
      the disturbance of the highest cerebral integrative functions, which is caused by
      the impairment of cerebral oxidative metabolism. Piracetam is effective on most
      neurotransmitter systems, without a specific receptor agonism or antagonism,
      increases the effectivity of different biogenic amine systems, has also an effect
      on membrane permeability, increases the concentration of NMDA (methyl-D
      aspartate) receptors in the impaired brain and improves cognitive functions. In
      the patients suffered from alcohol dependence piracetam produces positive
      morphologic changes, by decreasing lipofuscin accumulation. In early stage it
      prevents the development of delirium. Despite of the great number (approximately
      150) of medication that were tried in the treatment of delirium, the ideal one
      still has not been found. Among the accessible therapeutic possibilities the
      author searched for methods which make the treatment more effective. The
      administration of parental piracetam, therefore was brought into his
      therapeutical protocol. Parenteral piracetam--similarly to literature data-
      proved to be effective in the treatment of alcohol withdrawal delirium.
      Considering the present--insufficient--hospital financing, it is remarkable that
      though the costs of the new therapy are higher than the traditional meprobamat
      therapy, through less side effect it is more economical (overall costs lower) and
      by decreasing the time of delirium it is more humane to the patients.

PMID- 12809071
TI  - [Fetal uropathies and pulmonary hypoplasia].
AB  - The author discusses the role of fetal uropathies in the development of pulmonary
      hypoplasia. The predisposing abnormalities may occur at various locations,
      including the kidneys and the efferent urinary ducts (ureters, urocyst, urethra).
      Following a brief general overview of the normal development of the urinary
      system, the developmental abnormalities are discussed. These anomalies interfere
      with the secretion of urine or, alternatively, may hinder or obstruct its
      elimination through the urinary ducts, thus leading to oligohydramnios.
      Inadequate production of amniotic fluid hinders the respiratory movements and
      unfavourable affects or even arrests pulmonary development. The stage of lung
      maturity at the time of birth offers a key to the determination of the time of
      initial occurrence of pulmonary hypoplasia. Regretfully, the therapeutic options
      are rather limited, due to the substantial maternal and fetal risks of in utero
      fetal surgery. In case of valvula urethrae posterior, a vesico-amniotic shunt
      offers a realistic chance for success.

PMID- 12809070
TI  - [Treatment of acute porphyrias. The importance of follow-up of patients and
      carriers].
AB  - Acute porphyrias are caused by the inherited decreased activity of the enzymes of
      the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types
      of them: acute intermittent porphyria, porphyria variegata, coproporphyria and
      delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of
      their frequency. Basically the clinical picture is the same in the four types of
      acute porphyria. The most frequent complaints and symptoms are: cramping
      abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the
      advanced phase, there is a red-colored urine, hyponatremia, subileus, acute
      psychosis and Landry-type paralysis. Without proper treatment death is caused by
      respiratory paralysis or serious arrhythmia. In case of suspicion of acute
      porphyria it is mandatory to identify the type of the acute porphyria and the
      actual status of the patient. The later indicates what kind of treatment should
      be used. In the acute phase the early therapy with heme arginate is the treatment
      of choice. Since the clinical symptoms are precipitated by endogenous or
      exogenous inducing factors--most often by drugs-, the drugs negatively affecting
      the heme biosynthesis should be omitted at once even in the suspicion of acute
      porphyria. The role of the inducing factors in the manifestation of the clinical
      symptoms makes possible the prevention. It is possible to avoid the inducing
      factors and this way to prevent the acute attack if the acute porphyrias are
      recognized in time and the patients and the carriers are under regular control.
      The patients receive special identification card and the up-to-date list of safe
      drugs. They can use only these drugs in any kind of illness. Other drugs should
      be considered as porphyrinogenic since it is impossible to predict based on their
      chemical structure if they negatively affect the heme biosynthesis.

PMID- 12809072
TI  - [Prince Dr. Laszlo Batthyany-Strattmann, "physician of the poor" (1870-1931)].

PMID- 12809073
TI  - [Samuel Zay born 250 years ago (1753-1812)].

PMID- 12809074
TI  - Testosterone supplementation in men with type 2 diabetes, visceral obesity and
      partial androgen deficiency.
AB  - The objective of this study was to assess the effects of oral testosterone
      supplementation therapy on glucose homeostasis, obesity and sexual function in
      middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight
      middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of
      androgen deficiency, were included in this open-label study. Twenty-four subjects
      received testosterone undecanoate (TU; 120 mg daily, for 3 months); 24 subjects
      received no treatment. Body composition was analyzed by bio-impedance. Parameters
      of metabolic control were determined. Symptoms of androgen deficiency and
      erectile dysfunction were scored by self-administered questionnaires. TU had a
      positive effect on (visceral) obesity: statistically significant reduction in
      body weight (2.66%), waist-hip ratio (-3.96%) and body fat (-5.65%); negligible
      changes were found in the control group. TU significantly improved metabolic
      control: decrease in blood glucose values and mean glycated hemoglobin (HbA1c)
      (from 10.4 to 8.6%). TU treatment significantly improved symptoms of androgen
      deficiency (including erectile dysfunction), with virtually no change in the
      control group. There were no adverse effects on blood pressure or hematological,
      biochemical and lipid parameters, and no adverse events. Oral TU treatment of
      type 2 diabetic men with androgen deficiency improves glucose homeostasis and
      body composition (decrease in visceral obesity), and improves symptoms of
      androgen deficiency (including erectile dysfunction). In these men, the benefit
      of testosterone supplementation therapy exceeds the correction of symptoms of
      androgen deficiency and also includes glucose homeostasis and metabolic control.

PMID- 12809075
TI  - Age-related change in serum concentrations of testosterone in middle-aged Korean
      men.
AB  - The objective of this study was to determine whether testosterone and sex hormone
      binding globulin (SHBG) levels are different between healthy men and men with
      chronic illness, and to evaluate the age-related changes of testosterone and SHBG
      in healthy men in Korea. enrollment took place between January 2000 and December
      2001 at Pundang CHA General Hospital in Korea. All men who came for male
      climacteric and geriatric health screening examinations were eligible. Of the 762
      men recruited, 136 men had at least one present or previous medical illness and
      626 men were healthy. Higher serum concentrations of total testosterone (5.31 +/-
      1.88 ng/ml vs. 4.96 +/- 1.43 ng/ml; p < 0.05), free androgen index (16.60 +/-
      7.36 vs. 14.57 +/- 5.55; p < 0.01) and calculated bioavailable testosterone (8.88
      +/- 3.52 nmol/l vs. 7.91 +/- 2.52 nmol/l; p < 0.01) were demonstrated in the
      healthy compared with the disease group. Total testosterone declined at a rate of
      0.2% per year, SHBG increased by 1.74% per year, calculated bioavailable
      testosterone declined by 0.8% per year, and free androgen index declined by 1.15%
      per year in healthy subjects aged between 40 and 70. The above results seem to be
      consistent with previous Western studies, showing higher concentrations of
      testosterone in healthy men, that decline with increasing age.

PMID- 12809076
TI  - A pilot study on the effects of testosterone in hypogonadal aging male patients
      with Alzheimer's disease.
AB  - The male aging process brings about declines in hormonal function including a
      gradual decline in bioavailable testosterone levels. Animal studies suggest that
      testosterone modulates cognitive function through enhancing acetylcholine release
      and up-modulation of nicotinic receptors. Tau protein deposition is also affected
      by androgen supplementation in animals. We hypothesize that testosterone
      replacement in elderly hypogonadal males may improve cognition, in particular the
      visual-spatial domain. Thirty-six male patients with a new diagnosis of
      Alzheimer's disease had their total and bioavailable testosterone levels
      measured. None of the patients had been on acetylcholinesterase inhibitors. Ten
      of the 36 patients (28%) were deemed biochemically hypogonadal (total
      testosterone < 240 ng/dl or 7 nmol/l). Five of the hypogonadal patients were
      randomized to testosterone and five to placebo. Initial Alzheimer's Disease
      Assessment Scale cognitive subscale (ADAScog) and Mini Mental Status Examination
      (MMSE) ranged from 31 to 19 and from 17 to 22, respectively. The clock drawing
      test (CDT) and the pentagon-tracing portion of the MMSE were used as measures of
      visual-spatial abilities. Normal prostate-specific antigen (PSA) levels were
      essential before treatment with intramuscular testosterone, 200 mg every 2 weeks.
      Measurement of testosterone, complete blood count, lipids, PSA and
      neuropsychological cognitive tests were repeated at 3, 6, 9 and 12 months of
      treatment. In the testosterone-treated group, levels of total testosterone
      increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l (p
      = 0.11). Bioavailable testosterone also increased from a mean of 48.7 ng/dl to
      142 ng/dl or 1.39 nmol/l to 4.05 nmol/l (p = 0.10). PSA levels were also elevated
      from a mean of 0.98 to 1.37 ng/ml (p = 0.07). ADAScog improved from a mean of 25
      to 16.3 (p = 0.02); MMSE improved from a mean of 19.4 to 23.2 (p = 0.02), CDT
      also improved from 2.2 to 3.2 (p = 0.07). One patient stopped treatment because
      of hypersexual behavior. The placebo-treated group deteriorated gradually. This
      small pilot study performed in aging male patients suggests that testosterone
      could indeed improve cognition, including visual-spatial skills in mild to
      moderate Alzheimer's disease.

PMID- 12809077
TI  - The penalties of passion and desire: love and the aging male in early 20th
      century film.
AB  - In popular feature films of the 20th century, the aging male is generally
      presented as a kindly, if feeble, old grandfather or as a ruthless villain. A
      handful of films from this era broke with tradition and took the bold step of
      exploring the social and medical implications of latent sexual impulses in this
      age group. Love for aging males was typically presented as a dangerous aberration
      that held the promise of tragic consequences. This paper will demonstrate that
      cinematographic presentations of geriatric male sexuality faithfully adhere to
      the medical dogma of the day.

PMID- 12809078
TI  - Complementary psychometric methods in pharmaco-electroencephalography research.

PMID- 12809079
TI  - Electroencephalography and glucose metabolism (positron-emission tomography) in
      dementing disorders.

PMID- 12809080
TI  - Combining electroencephalography, functional magnetic resonance imaging and
      transcranial magnetic stimulation in the study of human cognition.

PMID- 12809081
TI  - Monitoring of disease progression and therapeutic efficacy in Alzheimer's disease
      by electrophysiological indices.

PMID- 12809082
TI  - Predicting response to antipsychotics by electrophysiological indices.

PMID- 12809083
TI  - Evoked potentials in psychiatry: psychophysiological meaning and clinical
      utility.

PMID- 12809084
TI  - Pharmaco-EEG in the first months of life.

PMID- 12809085
TI  - Pharmaco-electroencephalography in Phase I.

PMID- 12809086
TI  - Spatial EEG structure in schizophrenia.

PMID- 12809087
TI  - Prevention is treatment: prevention with positives in clinical care.

PMID- 12809088
TI  - HIV testing in correctional settings.

PMID- 12809089
TI  - Global fund to fight disease runs short.

PMID- 12809090
TI  - Global AIDS bill passes soundly in House, moves to Senate.

PMID- 12809091
TI  - Resolution urges PepsiCo to report impact of AIDS.

PMID- 12809092
TI  - Firms fumble for grip on HIV.

PMID- 12809093
TI  - Confidentiality. Australian court hears landmark HIV disclosure case.

PMID- 12809094
TI  - New testing helps CDC track HIV.

PMID- 12809095
TI  - U.S. House lauded for global leadership in passing AIDS funding bill.

PMID- 12809096
TI  - AIDS discrimination against funeral home dismissed.

PMID- 12809097
TI  - Glaxo drops drug prices, AIDS foundation drops suit.

PMID- 12809098
TI  - Anatomy of a successful campaign to lower AIDS drug prices.

PMID- 12809099
TI  - SSI. Disability benefits denied HIV-positive epileptic.

PMID- 12809100
TI  - Doctors sued for failure to offer prenatal HIV testing.

PMID- 12809101
TI  - GAO releases report on AIDS global fund.

PMID- 12809102
TI  - Enfuvirtide access, administration, and patient education.

PMID- 12809103
TI  - The optimal use of enfuvirtide.

PMID- 12809104
TI  - Drug profile: enfuvirtide (Fuzeon, ENF, T-20).

PMID- 12809105
TI  - More from CROI...new drugs: full pipeline, steady progress.

PMID- 12809106
TI  - Progress in pharmacology and drug interactions from the 10th CROI.

PMID- 12809107
TI  - Cytomegalovirus retinitis in 2003.

PMID- 12809108
TI  - A Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire:
      evaluation of questions about olfaction.
AB  - OBJECTIVE: A Scandinavian adaptation of the Multi-Clinic Smell and Taste
      Questionnaire (MCSTQ-Sc) was evaluated with respect to comprehension and test
      retest reliability for responses to questions about olfactory dysfunction
      (abnormal sensitivity, parosmia and phantosmia) and related questions about
      medical history and consequences of olfactory dysfunction. MATERIAL AND METHODS:
      Comprehension was evaluated in a first study in 20 patients with chief complaints
      of olfactory dysfunction by comparing questionnaire- and interview-based
      responses. Test-retest reliability was evaluated in a second study in 30 other
      patients with olfactory complaints. RESULTS: Data from the two studies suggest
      that the vast majority of the questions evaluated from the MCSTQ-Sc are
      comprehensible and generate responses with very good reliability. Distinct
      exceptions were poor agreement between the questionnaire- and interview-based
      responses for questions about the number of cigarettes smoked and the
      pleasantness and typical episode length of phantosmia; the test-retest
      reliability regarding the nostril side of phantosmia also showed poor agreement.
      The results suggest the importance of probing these areas further in the clinical
      interview. CONCLUSION: The findings imply that, with a few caveats, the MCSTQ-Sc
      is a useful tool for the clinical assessment of olfactory dysfunction and its
      consequences.

PMID- 12809109
TI  - Public health and aging: projected prevalence of self-reported arthritis or
      chronic joint symptoms among persons aged >65 years--United States, 2005-2030.
AB  - Arthritis and other rheumatic conditions are among the most common chronic
      diseases, affecting 70 million U.S. adults in 2001, and comprise the leading
      cause of disability among U.S. adults. Arthritis prevalence increases with age,
      affecting approximately 60% of the U.S. population aged >/= 65 years. As a result
      of better identification and treatment of other chronic diseases and lower
      mortality from infectious diseases, U.S. adults are living longer, and the U.S.
      population is aging. For this reason, the number of persons living with nonfatal
      but disabling conditions such as arthritis or chronic joint symptoms (CJS) might
      be increasing. To estimate the projected future burden of arthritis or CJS among
      persons aged >/= 65 years, CDC applied data from the 2001 Behavioral Risk Factor
      Surveillance System (BRFSS) to projected national population data for 2005-2030
      and state population data for 2025. This report summarizes the results of that
      analysis, which indicate that if arthritis prevalence rates remain stable, the
      number of affected persons aged >/= 65 years will nearly double by 2030. Proven
      public health interventions should be applied and new interventions developed to
      improve function, decrease pain, and delay disability among persons with
      arthritis, particularly those at highest risk for functional impairment and
      disability.

PMID- 12809110
TI  - Update: cardiac-related events during the civilian smallpox vaccination program-
      United States, 2003.
AB  - During the pre-event smallpox vaccination program, the U.S. Department of Defense
      (DOD) and CDC have received reports of cardiac events after vaccination. A case
      definition for myo/pericarditis as a smallpox vaccine--associated adverse event
      has been developed in conjunction with DOD, the joint Smallpox Vaccine Safety
      Working Group of the Advisory Committee on Immunization Practices (ACIP) and the
      Armed Forces Epidemiology Board (AFEB), and consulting cardiologists,
      immunologists, and epidemiologists. The term myo/pericarditis is used for
      surveillance purposes to refer to patients who have myocarditis, pericarditis, or
      both (myopericarditis). Myo/pericarditis cases are classified into suspected,
      probable, and confirmed categories. Suspected cases include those that are
      investigated and reported, although the level of certainty for the diagnosis is
      lower. These definitions were used to categorize all cardiac-related reports
      among civilian vaccinees received through May 9, 2003; a total of 21 cases of
      myo/pericarditis were ascertained. All have been reported previously; however,
      some have been reclassified. In addition, nine cases of ischemic cardiac events
      (i.e., myocardial infarction [MI] or angina) among civilian vaccinees have been
      reported previously. This report includes the case definition of myo/pericarditis
      and updates information on all reports of cardiac adverse events among 36,217
      civilian vaccinees since the beginning of the civilian smallpox vaccination
      program reported through May 9 to CDC from the Vaccine Adverse Event Reporting
      System (VAERS).

PMID- 12809111
TI  - State Medicaid coverage for tobacco-dependence treatments--United States, 1994
      2001.
AB  - Tobacco use is the leading preventable cause of death in the United States. One
      of the national health objectives for 2010 is to increase insurance coverage of
      evidence-based treatment for nicotine dependence (i.e., total coverage of
      behavioral therapies and Food and Drug Administration [FDA]--approved
      pharmacotherapies) in Medicaid programs from 36 states to all states and the
      District of Columbia (DC) (objective 27.8). To increase both the use of treatment
      by smokers attempting to quit and the number of smokers who quit successfully,
      the Guide to Community Preventive Services recommends reducing the "out-of
      pocket" cost of effective tobacco-dependence treatments (i.e., individual, group,
      and telephone counseling, and FDA--approved pharmacotherapies) for smokers. The
      2000 Public Health Service (PHS) Clinical Practice Guideline supports expanded
      insurance coverage for tobacco-dependence treatments. In 2000, approximately 32
      million low-income persons in the United States received their health insurance
      coverage through the federal-state Medicaid program; 11.5 million (36%) of these
      persons smoked (CDC, unpublished data, 2000). The amount and type of coverage for
      tobacco-dependence treatment offered by Medicaid has been reported for 1998 and
      2000 from state surveys conducted by the Center for Health and Public Policy
      Studies (CHPPS) at the University of California, Berkeley. All states and DC were
      re-surveyed in 2001 about amount and type of coverage, and level of coverage
      since 1994. This report summarizes the results of the survey, which indicate that
      the number of Medicaid programs providing some coverage for tobacco-dependence
      counseling or medication increased from 34 in 2000 to 36 in 2001, but only one
      state offered coverage for all the counseling and pharmacotherapy treatments
      recommended by the 2000 PHS guideline. If the 2010 national health objective is
      to be achieved, Medicaid coverage for treatment of tobacco dependence should be
      increased dramatically.

PMID- 12809112
TI  - Update: severe acute respiratory syndrome--United States, May 28, 2003.
AB  - CDC continues to work with state and local health departments, the World Health
      Organization (WHO), and other partners to investigate cases of severe acute
      respiratory syndrome (SARS). This report updates SARS cases reported worldwide
      and in the United States and reports a seventh laboratory-confirmed U.S. case.

PMID- 12809113
TI  - [Johann Hedwig (1730-1799), an eminent physician and botanist from Transylvania].

PMID- 12809115
TI  - Reflections of an Egyptian surgeon visiting Nippon Medical School.

PMID- 12809114
TI  - You're the flight surgeon.  A new smoking cessation program.

PMID- 12809116
TI  - An introduction to the general surgery department at Cairo University.

PMID- 12809117
TI  - The socioeconomic impact of gambling: the Whistler Symposium.

PMID- 12809118
TI  - [The Guillain-Barre syndrome].

PMID- 12809119
TI  - [Combined treatment of multiple sclerosis. A case report].

PMID- 12809120
TI  - Experimental cadaveric study of lateral impact of the pelvis in children.
AB  - OBJECTIVE: To study the mechanic response of children's pelvis to lateral impact.
      METHODS: Twelve 2-to 12 year-old children's cadavers were donated by their
      relatives for this impact test, dividing into younger group (2 to 4 years old,
      n=6) and elder group (5 to 12 years old, n=6). CT scan and X-ray examination were
      performed before the impact test, and after the test, X-ray examination and
      autopsy were conducted. All the pelvises were impacted at a speed of 7.5+/-0.5
      m/s but for one at 9.1m/s. RESULTS: All tests showed similar behavior of the
      pelvis with similar timing and peak viscous criterion (V*C) values. Statistical
      significance was noted in the maximum V*C and degree of stiffness of the pelvis
      between the 2 groups (P<0.05). No injuries occurred in the 2 groups after the
      impact. CONCLUSION: The pelvic test yields very repeatable pelvic response among
      each group tested.

PMID- 12809121
TI  - [Muscle pseudohypertrophy associated with hypothyroidism (Hoffman's syndrome)].

PMID- 12809122
TI  - [Transilluminated powered phlebectomy for varicose veins of the lower extremity:
      report of one case].

PMID- 12809124
TI  - Why is St. Mary's the exception?

PMID- 12809123
TI  - Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse
      axonal injury: a pilot double-blind randomized trial.

PMID- 12809126
TI  - Can staff handle the truth?

PMID- 12809125
TI  - Sharing patient safety data.

PMID- 12809127
TI  - 1Q[3a]. Do teaching hospitals need sweeping changes?

PMID- 12809128
TI  - Humble beginnings.

PMID- 12809130
TI  - [Roundtable: Cross reactions to food allergens. Introduction].

PMID- 12809132
TI  - [The beginnings of dental training in Transylvania].

PMID- 12809131
TI  - [Normative documents of the Spanish Society for Pediatric Clinical Immunology and
      Allergology. Minimum requirements for practicing the specialty of pediatric
      allergy and immunology in a hospital setting].

PMID- 12809133
TI  - Environmental consequences of impact cratering events as a function of ambient
      conditions on Earth.
AB  - The end of the Mesozoic Era is defined by a dramatic floral and faunal turnover
      that has been linked with the Chicxulub impact event, thus leading to the
      realization that impact cratering can affect both the geologic and biologic
      evolution of Earth. However, the environmental consequences of an impact event
      and any subsequent biological effects rely on several factors, including the
      ambient environmental conditions and the extant ecosystem structures at the time
      of impact. Some of the severest environmental perturbations of the Chicxulub
      impact event would not have been significant in some periods of Earth history.
      Consequently, the environmental and biological effects of an impact event must be
      evaluated in the context in which it occurs.

PMID- 12809134
TI  - Large aerial bursts: an important class of terrestrial accretionary events.
AB  - Large aerial bursts similar to the 1908 Tunguska bolide but much larger in
      magnitude have surely been responsible for many catastrophic events in the
      history of the Earth. Because aerial bursts produce shallow (or even negligible)
      craters, their existence is difficult to document in the geological record. Even
      aerial bursts as small as Tunguska deposit enough energy to melt approximately
      1mm of dry soil. Silica-rich glass formed in such melts has the potential to
      survive in the soil for many Ma, thus a potential indicator of large aerial
      bursts is glass that was formed as thick regions within silicate melt sheets. The
      layered tektites from Southeast Asia and the Libyan desert glass may have formed
      by a combination of sedimentation and downslope flow of silicate melt heated by
      radiation from large aerial bursts. The alternative, formation of layered
      tektites as crater ejecta, cannot account for observations such as uniformly high
      10Be contents, the orientation of the magnetic remanence field, and the absence
      of splash-form (e.g., teardrop or dumbbell) tektites in regions where layered
      tektites are common. The largest asteroids or comets make craters no matter what
      their strength. Recent reviews suggest that, for events in the energy range up to
      10(19)-10(20) J (about two orders of magnitude larger than the Meteor Crater
      impact), aerial bursts are more likely than cratering events, and the layered
      tektites of Southeast Asia imply the existence of aerial bursts one to two orders
      of magnitude larger still.

PMID- 12809135
TI  - Misleading meta-analysis.

PMID- 12809136
TI  - Smokeless tabacco.

PMID- 12809137
TI  - VA program bridges skills gap, improves performance.

PMID- 12809138
TI  - Focus on butterfly eyespot development.
AB  - The beautiful eyespot patterns on the wings of butterflies help them to evade
      predators, but they also present biologists with a unique opportunity to
      investigate the reciprocal interactions of development and evolution.

PMID- 12809139
TI  - Development, plasticity and evolution of butterfly eyespot patterns.
AB  - The developmental and genetic bases for the formation, plasticity and diversity
      of eyespot patterns in butterflies are examined. Eyespot pattern mutants,
      regulatory gene expression, and transplants of the eyespot developmental
      organizer demonstrate that eyespot position, number, size and colour are
      determined progressively in a developmental pathway largely uncoupled from those
      regulating other wing-pattern elements and body structures. Species comparisons
      and selection experiments suggest that the evolution of eyespot patterns can
      occur rapidly through modulation of different stages of this pathway, and
      requires only single, or very few, changes in regulatory genes.

PMID- 12809140
TI  - Practice brief. Internet resources for HIM professionals.

PMID- 12809141
TI  - Evidence for trends in heavy rainfall events over the UK.
AB  - Daily precipitation in the UK has changed over the period 1961-2000, becoming on
      average more intense in winter and less intense in summer. Recent increases in
      total winter precipitation are shown to be mainly due to an increase in the
      amount of precipitation on wet days, with a smaller contribution in the western
      UK from a trend towards more wet days. If the wet-day amounts are modelled using
      a gamma distribution, then positive trends in its scale parameter are found
      across almost all of the UK, consistent with an increased frequency of heavy
      winter precipitation. Non-parametric analyses confirm an increase in the
      contribution of heavy events to winter precipitation totals. Analysis of multi
      day sequences of heavy rainfall indicate a corresponding increase in their
      frequency. Results for summer show almost opposite trends: decreased
      precipitation totals (driven more equally by fewer wet days and reduced wet-day
      amounts), decreases in gamma scale parameter (although accompanied by a trend
      towards a less positively skewed distribution) and decreases in the occurrence of
      heavy precipitation (whether defined parametrically or non-parametrically). A
      more sparse network of weather stations with data back to 1901 suggests that the
      recent winter changes are unusual, while the recent summer changes are not,
      though the poorer coverage reduces the confidence in these longer-period results.

PMID- 12809145
TI  - Preventing suicide--are we?

PMID- 12809142
TI  - Behavioral health issue brief: co-occurring mental illness and drug addiction
      treatment: overview and bibliography: year end report - 2002.

PMID- 12809146
TI  - Child and adolescent survivors of suicide.
AB  - Suicide in a family is distressing for each and every member. Children and
      adolescents bereaved by suicide are known to be more at risk of suffering from a
      variety of psychiatric problems, especially affective disorders. A group of
      children and adolescents who experienced a suicidal death in the family were
      assessed for psychiatric problems as well as for social adjustment. The findings
      suggest that the bereaved children and adolescents are at elevated risk for major
      depressive disorder, posttraumatic stress disorder, and impaired social
      adjustment.

PMID- 12809147
TI  - Can a theory of suicide predict all "suicides" in the elderly?
AB  - Older adults consistently have the highest rates of suicide in most societies.
      Despite the paucity of studies until recently, research has shown that suicides
      in later life are best understood as a multidimensional event. An especially
      neglected area of research is the psychological/psychiatric study of personality
      factors in the event. This paper outlines one comprehensive model of suicide and
      then raises the question: Is such a psychiatric/psychological theory applicable
      to all suicides in the elderly? To address the question, I discuss the case of
      Sigmund Freud; raise the topic of suicide and/or dignified death in the
      terminally ill; and examine suicide notes of the both terminally ill and
      nonterminally ill elderly. I conclude that, indeed, greater study and theory
      building are needed into the "suicides" of the elderly, including those who are
      terminally ill.

PMID- 12809148
TI  - The death of offenders in England and Wales.
AB  - The death of offenders in the community has received considerably less attention
      than the death of prisoners, although limited research suggests that community
      offenders may be even more vulnerable to death than prisoners. This study
      compared the nature and extent of death among prisoners (n = 236) and offenders
      serving community sentences or ex-prisoners receiving postcustodial supervision
      by the Probation Service (n = 1,267) in England and Wales in 1996 and 1997.
      Information contained in death certificates was used to code for mode of death.
      Prisoners and community offenders were found to be reasonably similar in
      vulnerability to suicide/self-inflicted death; however, the risk of accidental
      death and homicide was greater for community offenders, and drugs and alcohol
      played a bigger part in their deaths. The policy implications of the findings are
      discussed.

PMID- 12809149
TI  - Suicidal behavior in black South Africans.
AB  - In the past suicidal behavior among Black South Africans has been largely
      underresearched. Earlier studies among the other main ethnic groups in the
      country showed suicidal behavior in those groups to be a serious problem. This
      article briefly reviews some of the more recent research on suicidal behavior in
      Black South Africans. The results indicate an apparent increase in suicidal
      behavior in this group. Several explanations are offered for the change in
      suicidal behavior in the reported clinical populations. This includes past
      difficulties for all South Africans to access health care facilities in the
      Apartheid (legal racial separation) era, and present difficulties of post
      Apartheid transformation the South African society is undergoing, as the people
      struggle to come to terms with the deleterious effects of the former South
      African racial policies, related socio-cultural, socio-economic, and other
      pressures.

PMID- 12809150
TI  - Networking to support suicide survivors.
AB  - This paper is the first report on a national program for increasing bereavement
      support for suicide survivors in the Flemish region in Belgium. A Working Group
      consisting of representatives of a wide variety of mental health institutions,
      social programs, and suicide survivor groups in the area determined that a
      program developing networks between the services seems to hold the greatest
      promise for both an increase in the number of services available and an
      improvement in the quality of services offered.

PMID- 12809151
TI  - Anguish and despair in adolescents with eating disorders--helping to manage
      suicidal ideation and impulses.
AB  - Adolescents struggling against anorexia nervosa or bulimia nervosa often
      experience self-punishing thoughts and behaviors, including self-mutilation, and
      suicidal ideation and attempts. These arise out of the profound anguish and
      despair frequently experienced by these young people. This paper outlines four
      particularly salient clinical themes underlying this despair that have
      significant implications for treatment. A practice perspective is discussed which
      emphasizes empathic listening and the development of a strong therapeutic
      alliance with the adolescent. Treatment recommendations draw from narrative
      theory and practice, and from feminist perspectives. The paper also draws on
      cognitive therapy and on recent developments in the areas of spirituality and
      motivational enhancement. Involving the distressed adolescent's family is also
      addressed.

PMID- 12809152
TI  - Victims and survivors--letter across the pacific.

PMID- 12809153
TI  - Deinstitutionalization and suicide.

PMID- 12809154
TI  - Evaluation of the pupillary light response as an objective measure of visual
      function.
AB  - Examination of the pupil provides critical objective information that complements
      subjective visual measurements and can provide important clues for distinguishing
      among different etiologies of loss of visual function. Although automated
      technologies and pupillary perimetry provide valuable insight into the
      correspondence between visual and pupillary dysfunction, a firm understanding of
      the principles of the afferent examination of the pupil is all that is required
      for the clinician to quickly obtain this objective measure of function during any
      routine examination.

PMID- 12809155
TI  - Visual acuity and its measurement.
AB  - Despite its critical importance to our daily life, the most common measurement of
      visual function, visual acuity, is a relatively crude and narrow one testing only
      a small portion of the broad range of visual functions. Visual acuity is the
      measurement of the ability to discriminate two stimuli separated in space at high
      contrast relative to the background. Clinically, this is measured by asking the
      subject to discriminate letters of known visual angle. The visual acuity is
      represented as the reciprocal of the minimal angle of resolution (the smallest
      letters resolved) at a given distance and at high contrast. Other measurements of
      visual acuity also exist, including Vernier acuity. Newer charts, such as the
      ETDRS chart, use letters of equal recognition difficulty and use the log of the
      minimal angle of resolution; these charts have significant advantages over the
      old Snellen-type charts. This article reviews visual measurements in children and
      in patients with low vision, and it reviews factors affecting visual acuity, such
      as pupil size, refractive error, media opacities, and pharmacologic agents.

PMID- 12809156
TI  - Contrast sensitivity.
AB  - Spatial contrast is a physical dimension referring to the light-dark transition
      of a border or an edge in an image that delineates the existence of a pattern or
      an object. Contrast sensitivity refers to a measure of how much contrast a person
      requires to see a target. Contrast-sensitivity measurements differ from acuity
      measurements; acuity is a measure of the spatial-resolving ability of the visual
      system under conditions of very high contrast, whereas contrast sensitivity is a
      measure of the threshold contrast fur seeing a target. Today the most common
      methods for measuring contrast sensitivity are chart-based systems that can be
      mounted on the wall. These charts use test targets that are either sine-wave
      gratings or letters. Which specific chart a clinician selects should be guided by
      his or her purpose in using contrast sensitivity for patient management. In the
      research setting, chart selection should rest on ensuring that the scientific
      aims of the study are met. Contrast-sensitivity tests can provide useful
      information by revealing in some conditions visual loss not identifiable through
      visual acuity tests, by providing another method of monitoring treatments, and by
      providing a better understanding of visual performance problems faced by persons
      with vision impairment.

PMID- 12809157
TI  - Color vision.
AB  - Many visual disorders produce acquired color vision defects. Color vision theory
      emphasizes several stages of visual processing: prereceptoral filters (lens,
      macular pigment, pupil), cone photopigments (L-, M-, and S-cones), and
      postreceptoral processes (red-green, S-cone, and luminance channels). Congenital
      color defects, which affect 8% to 10% of males and 0.4% to 0.5% of females,
      result from alterations in the photopigment absorption spectra or the absence of
      one or more photopigments. The most common defects are color vision deficiencies
      (protan and deutan defects), which are milder than the rarer achromatopsias
      (complete loss of color vision). Acquired color vision defects can be attributed
      to a number of different causes: alteration of prereceptoral filters, reduced
      cone photopigment optical density, greater loss of one cone type than the others,
      and disruption of postreceptoral processes. Acquired color vision defects have
      been divided into three classes: type 1, red-green defect with scotopization;
      type 2, red-green defect without scotopization; and type 3, blue defects (with or
      without pseudoprotanomaly). Blue defects are usually type 3 acquired defects
      because congenital tritan defects have an incidence of one in several tens of
      thousands. Red-green defects can be acquired or congenital, and ruling out
      acquired defects can require a battery of tests (plates and arrangement tests,
      anomaloscopy, perhaps genetic analysis). Color vision tests must be administered
      carefully (with a standard illuminant and protocol), and pupillary miosis or high
      lens density should be noted and their possible effects considered when
      interpreting test results. Plate tests provide a simple screening method but do
      not provide a diagnosis. Arrangement tests and anomaloscope testing take more
      time and make greater demands on the tester, but they provide a more thorough
      evaluation. When standard protocols are followed and results are interpreted in
      terms of prereceptoral filters, photopigment optical density, cone loss, and
      disruption of postreceptoral processes, a battery of color vision tests can be
      useful in the differential diagnosis, after progression of the disease, and for
      evaluating the effectiveness of treatment.

PMID- 12809158
TI  - Standard perimetry.
AB  - As distinguished from measuring the ability to see at the location where the
      eye's gaze is fixated, perimetry consists of determining the visual capabilities
      throughout the field of vision. Traditionally the ability to see a white object
      or a projected spot of white light is determined and quantified under standard
      conditions. Modern machines use automated methods to present spots of light in a
      programmed manner to determine the threshold of visual capability, and, after
      recording the data, these machines also apply statistical analyses of the results
      to assist the clinician in evaluation of the patient. New methods for testing
      particular aspects of visual function and analyzing the results are continuously
      under development.

PMID- 12809159
TI  - Frequency-doubling technology perimetry.
AB  - The FDT perimeter is a compact and relatively inexpensive perimeter whose
      transportability, tolerance to refractive errors, and rapid test times (less than
      1 minute per eye) make it a suitable candidate for visual field screening. It is
      a uniform finding that the C-20-1 screening protocol of the FDT perimeter
      provides good sensitivity and specificity for the detection of moderate and
      severe losses in glaucoma. Sensitivity can be increased by use of the C-20-5
      screening protocol. In addition, the FDT perimeter demonstrates good sensitivity
      and specificity for detecting the presence of neuro-ophthalmic disorders, though
      it may have a limited ability to determine whether a field defect is hemianopic.
      There is only limited evidence that the FDT can appropriately detect retinal
      disease. Despite some evidence that the current FDT perimeter may be suitable for
      staging and monitoring the progression of visual field damage, the large targets
      used in the test make this of limited practicability. The development of a
      frequency-doubling test with smaller targets spaced over narrower intervals would
      improve the ability of FDT perimetry to determine the spatial extent of visual
      field defects.

PMID- 12809160
TI  - Short-wavelength automated perimetry.
AB  - Short-wavelength automated perimetry (SWAP) is a visual field test designed to
      assess the short-wavelength sensitive color system by isolating the blue-yellow
      pathway. SWAP is a powerful clinical tool able to detect visual field deficits 3
      to 5 years before standard automated perimetry (white-on-white) in most glaucoma
      patients, and progression of visual field defects up to 3 years earlier. SWAP
      deficits are predictive of the onset and location of future visual field loss,
      and they correlate well with structural damage associated with glaucoma. The main
      disadvantage of SWAP remains the longer testing time required. In the clinic, it
      is recommended that SWAP be performed on patients who are at higher risk for
      glaucoma. Although SWAP was originally developed to detect visual loss in
      glaucoma patients, it is also useful for patients with diabetic retinopathy and
      maculopathy, optic neuropathies, vision loss associated with HIV, migraine, and
      multiple sclerosis. More sensitive psychophysical tests of visual function, such
      as SWAP, can significantly shorten clinical trials and aid in the validation of
      new therapeutic approaches.

PMID- 12809161
TI  - Electrophysiology.
AB  - Numerous electrophysiologic tests are available for use in the clinic. When
      properly recorded and analyzed, these tests provide important diagnostic and
      prognostic information about the site and nature of the disease process. If the
      results from these tests are combined with psychophysical findings (color vision,
      acuity, visual fields), their usefulness in defining disease can be further
      extended.

PMID- 12809162
TI  - Vision testing in the pediatric population.
AB  - The goal of office testing of the child remains the same as it is for the adult-
      to gather as much information as efficiently as possible. Clinical testing of the
      child requires familiarity with the limitations available tests. Perhaps most
      important is the ability choose the proper test to use at every development
      stage. Cooperation may be surprisingly good in to hands of experienced examiners,
      though very young children can be unpredictable. The general ophthalmologist
      should not fear having young patients but rather take joy in the interaction with
      them. Armed with as many tools as possible, the challenge of testing children can
      be converted to the reward of helping families.

PMID- 12809163
TI  - Practical assessment of vision in the elderly.
AB  - In this article we have demonstrated the significant visual impairments in elders
      with good vision by standard measures when the viewing conditions are less than
      ideal--low contrast, low or changing light level, or glare. Much of this
      impairment can be accounted for by the known age-related changes in the eye. We
      have emphasized that two people of the same age with the same standard acuity can
      have dramatically different vision under these nonideal conditions. Because one
      cannot predict vision under these conditions on the basis of standard acuity, it
      is important to use these additional measures. These other vision measures are
      more closely related to task performance (reading, face recognition) than
      standard acuity. We find that persons who perform poorly on these low-contrast
      measures are more likely to have significant losses of standard acuity in the
      future. Hence, these measures help identify persons who should be more closely
      monitored. Each of the vision functions shows significant decline across age. It
      is important to recognize that a 60-year-old with 20/30 acuity is different from
      an 80-year-old with the same acuity. The older person is more likely to be
      impaired under the conditions of daily life. Measurement and appreciation of
      visual function should allow better understanding of subjective visual symptoms
      and allow the clinician to offer appropriate advice for mitigating these
      impairments. Often simple interventions, such as correcting refractive error,
      improving lighting, avoiding large changes in light level, increasing contrast,
      and avoiding glare (perhaps through cataract surgery), can greatly improve not
      only vision function but quality of life. Many studies have reported that good
      vision allows for independent living, which is the goal for most elders.

PMID- 12809164
TI  - Real-world evaluation of visual function.
AB  - Visual function declines with age in a variety of ways. It must also be kept in
      mind, however, that the results reported here are primarily group findings. When
      evaluating the performance of older persons, there is extremely wide variability,
      and even though average performance may decline as a function of age, many older
      adults maintain excellent visual function throughout their lifetimes. It is
      important to keep the variability of individual performance in mind to avoid
      ageist stereotypes. Although declines in age-related vision are well documented,
      it is less clear why these declines have occurred. Most recent studies have
      controlled for criterion differences by using forced-choice methods. These
      studies confirm that even after correcting for differences in threshold criteria,
      age-related declines persist. Many other studies have controlled for optical
      changes using a variety of techniques. Again, some age-related declines still
      exist Although it is widely believed that the neuroanatomy and physiology of the
      visual pathways are affected by aging, there is still relatively little
      understanding of how these changes impact visual function. Thus, there is a need
      for further studies to link potential neural mechanisms to observed changes in
      functional visual performance. Furthermore, there is also a possibility that
      there may be multiple sites of decline within a given person and that these sites
      of decline may vary across persons. Thus, the use of an individual-differences
      approach is needed to evaluate the many potential explanations for sensory
      decline. Finally, there is frequently a discrepancy between performance in the
      laboratory and real-world performance. In trying to predict the performance of
      real-world tasks and in designing the best environments for the elderly, sensory
      function should not be considered in isolation. Rather contributing factors such
      as cognitive ability, expectations, distractions, and other health-related and
      motor problems must also be considered. Traditional clinical measures of visual
      function, though appropriate for evaluating the presence of disease, are often
      inadequate in explaining everyday performance impairments. Thus, further research
      is needed to fully understand the complex interactions between sensory,
      cognitive, motor, economic, and physical factors that together determine one's
      level of ability or disability in everyday tasks.

PMID- 12809165
TI  - Effect of a multidisciplinary program of weight reduction on endothelial
      functions in obese women.
AB  - Obesity is associated with an increased risk of developing atherosclerosis and
      atherosclerotic lesions are essentially an inflammatory response. The aim of this
      study was to evaluate the effect of a medically supervised, multidisciplinary
      weight loss program on endothelial functions and circulating levels of
      proinflammatory cytokines in obese women. Twenty healthy pre-menopausal obese
      women and 20 age-matched normal weight women were studied. Endothelial functions
      were assessed by evaluating the response of blood pressure and platelet
      aggregation to an intravenous bolus of L-arginine (3 g), the natural precursor of
      nitric oxide. In obese women, the vascular and rheological responses to L
      arginine were significantly lower (p < 0.05) at baseline, as compared with non
      obese women, indicating endothelial dysfunction; on the contrary, basal
      concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6) were significantly higher (p < 0.01). After one year of a multidisciplinary
      program of weight reduction consisting of diet, exercise and liposuction surgery,
      all obese women lost at least 10% of their original weight (10.5 +/- 1.7 kg,
      range 7.9-13.9 kg). Compared with baseline, sustained weight loss was associated
      with reduction of cytokine (p < 0.01) concentrations and with improvement of
      vascular responses to L-arginine. In conclusion, a multidisciplinary approach
      aimed at inducing a sustained reduction of body weight in obese women is feasible
      and is associated with improvement of endothelial functions and reduction of
      circulating proinflammatory cytokine concentrations.

PMID- 12809166
TI  - GH secretagogues and hypothalamo-pituitary-adrenal axis.

PMID- 12809167
TI  - Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine
      activity of acylated ghrelin in humans.
AB  - Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, displays
      strong GH-releasing activity mediated by the GH secretagogue (GHS)-receptor (GHS
      R) type 1a at the hypothalamus-pituitary level. Ghrelin and synthetic GHS also
      possess other GH-independent peripheral endocrine and non-endocrine activities
      via the activation of peripheral GHS-R subtypes. In rats in vivo non-acylated
      ghrelin has been reported devoid of any endocrine activity; however, in vitro, it
      has been shown as effective as ghrelin in exerting anti-proliferative activity on
      tumor cell lines. The aim of the present study was to clarify whether non
      acylated human ghrelin shares some of the endocrine activities of its acylated
      form in humans. To this goal, the effects of acylated or non-acylated ghrelin
      (1.0 microg/kg i.v. at 0 min) on GH, PRL, ACTH, F, insulin and glucose levels
      were studied in two different testing sessions in 7 normal young volunteers (age
      [mean +/- SE]: 24.3 +/- 1.7 yr; BMI: 21.5 +/- 0.9 kg/m2). The effects of placebo
      administration were also studied. The administration of acylated ghrelin induced
      prompt and marked increase in circulating GH levels (AUC: 5452.4 +/- 904.9
      microg*min/l; p < 0.01 vs placebo) and significant increase in PRL (1273.5 +/-
      199.7 microg*min/l; p < 0.01 vs placebo), ACTH (4482.7 +/- 954.4 pg*min/ml; p <
      0.01 vs placebo) and F levels (15985.0 +/- 1141.9 microg*min/l; p < 0.01 vs
      placebo). Its administration was also followed by decrease in insulin levels
      (1448.67 +/- 137.9 mU*min/l; p < 0.05 vs placebo) that was coupled with an
      increase in plasma glucose levels (10974.2 +/- 852.5 mg*min/dl; p < 0.05 vs
      placebo). The administration of non-acylated ghrelin and that of placebo did not
      induce any change in the hormonal parameters or in glucose levels. In conclusion,
      this study shows that in humans nonacylated ghrelin does not possess the
      pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in
      Serine 3.

PMID- 12809168
TI  - Effects of non-specific vs individualized exercise training protocols on aerobic,
      anaerobic and strength performance in severely obese subjects during a short-term
      body mass reduction program.
AB  - The purpose of the present study was to compare aerobic, anaerobic and strength
      performance changes induced by two short-term (3-week) body mass reduction
      programs based on the same low-calory diet (1200-1500 kcal/day), nutritional
      education and psychological counseling, but entailing different exercise training
      protocols. An individualized, low-volume and moderate-intensity exercise training
      (IET) was contrasted with a non-specific, high-volume, low-intensity exercise
      training (NET). Thirty obese in-patients (12 males, 18 females; mean age +/- SD:
      33.9 +/- 9.4 yr, range: 19-51yr; mean BMI: 40.5 +/- 3.8 kg/m2, range: 35.3-51.4
      kg/m2) were randomly divided in two gender-matched groups of 15 subjects each
      undergoing a different exercise training protocol. Maximum oxygen uptake (VO2max)
      determined with a submaximal indirect test on a bicycle ergometer, lower limb
      maximum power output (W(max)) determined with the jumping method, global motor
      capabilities determined by analysis of locomotor pattern during a short (8 m)
      running, maximum strength (1-RM) of upper and lower limb muscle groups determined
      with isotonic machines were tested before and after the program. Adherence to an
      individual exercise activity and maintenance of body weight (bw) loss were
      evaluated with a telephonic interview 6 months after the completion of the
      program. In both groups a significant (p < 0.001) and comparable weight loss was
      observed (IET: -4.27%; NET: -4.17%). In both groups VO2max and W(max) increased
      significantly (p < 0.05-0.001) when expressed relatively to body mass, while in
      absolute terms they were significantly (p < 0.001) improved only in IET group. 1
      RM in all tested muscle groups was significantly increased in both IET and NET
      subjects (p < 0.001-0.01), but improvements were significantly greater in IET as
      compared with NET (p < 0.05-0.001). The analysis of locomotor pattern during the
      short running indicated that IET subjects significantly improved their global
      motor capabilities (p < 0.05-0.001), while no change was observed in NET group.
      After 6 months, IET subjects reported a level of spontaneously chosen physical
      activity significantly higher (p < 0.05) than NET subjects, displaying a trend of
      further decrease in bw. It was concluded that, although no difference in bw loss
      was appreciated between the two studied groups and significant improvements were
      found also in subjects performing NET protocol, the IET protocol offers better
      overall results in terms of muscle performance and physical fitness, with a
      possibly stronger motivation to subsequent exercise activity.

PMID- 12809169
TI  - Acute goserelin administration inhibits gonadotropin and androgen secretion in
      post-menopausal women with ovarian hyperandrogenism.
AB  - The aim of this study was to verify the effect of goserelin, a GnRH agonist, in
      women with post-menopausal virilization. Six patients with post-menopausal
      virilization and increase in 17-hydroxyprogesterone (17-OHP), total (TT) and free
      testosterone (FT) levels underwent single subcutaneous administration of
      goserelin, 3.6 mg. Serum 17-OHP, TT, FT, LH, FSH, E2, delta4 and 3alpha-andro
      stanediol glucuronide levels were measured before and 4, 8 and 18 days after
      goserelin administration. Goserelin administration was followed by progressive
      inhibition of FSH and LH, which fell to premenopausal levels on day 18, and
      progressive normalization of androgen parameters. The low E2 levels recorded at
      baseline were further reduced by goserelin administration. Four patients then
      underwent ovariectomy while in two patients, rejecting surgical treatment,
      goserelin treatment was protracted up to 6 and 12 months, respectively, with
      remission of hyperandrogenism. This study shows that in post-menopausal patients
      with virilization GnRH agonist allows to confirm the diagnosis of gonadotropin
      dependent ovarian hyperandrogenism: its administration induces inhibition of
      gonadotropin levels, normalization of androgen parameters, and remission of
      virilization when the treatment is protracted in patients waiting for surgery.

PMID- 12809170
TI  - Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-GLy) on melatonin
      secretion by the pineal gland of young and old rats.
AB  - The pineal gland contains many peptides known to be implicated in melatonin
      production. We examined the effects of a synthetic pineal tetrapeptide Ala-Glu
      Asp-Gly on melatonin secretion by the pineal gland. The tetrapeptide effects on
      pineal gland melatonin secretion were studied in young (9 weeks) and old (27
      months) male Wistar rats using a perifusion device. Pineal tetrapeptide at the
      concentrations used (10(-4) to 10(-6) M) had no significant effect upon melatonin
      secretion whatever the age of the animals, young or old. We also looked at the
      effect of the tetrapeptide on pineal melatonin stimulated by a beta-adrenergic
      agonist, isoproterenol. We found that isoproterenol-induced melatonin increase
      was not modified by the tetrapeptide. Our results suggest that the pineal
      tetrapeptide Ala-Glu-Asp-Gly, does not seem to play a role, at least in vitro, in
      the control of melatonin secretion by the rat pineal gland.

PMID- 12809171
TI  - Elevated concentrations of C-reactive protein in subjects with type 2 diabetes
      mellitus are moderately influenced by glycemic control.
AB  - The aim of this study was to establish whether glycemic control results in
      decrease of C-reactive protein (CRP) in Type 2 diabetic subjects. Newly diagnosed
      Type 2 diabetic subjects were recruited and followed-up by 6-month intensive
      medical management. All the participants were carefully interviewed, clinically
      examined, and laboratory tested to exclude conditions likely to provoke an
      inflammatory response, which was an exclusion criterium. CRP was measured by
      automated microparticle enzyme immunoassay (IMx, Abbott Laboratories, USA). Two
      hundred and forty-eight patients were included in the analysis of data. At
      baseline, average CRP levels were of 9.6 +/- 6.2 mg/l. Only 14 (5.7%) patients
      showed a fasting glucose equal or lower than 6.1 mmo/l (5.6 +/- 0.4 mmo/l); of
      them, 6 (42.8%) had elevated CRP levels (8.8 +/- 6.7 mg/l). The fasting glucose
      in the 234 (94.3%) non-controlled subjects was 13.1 +/- 4.8 mmol/l; of them 179
      (76.5%) subjects showed elevated CRP levels (10.9 +/- 6.5 mg/I). At the end of
      the 6-month follow-up, the average fasting glucose and HbA1c in the overall group
      decreased from 12.5 +/- 5.0 to 9.0 +/- 1.6 mmol/l, p < 0.00001, and 13.0 +/- 4.9
      to 8.9 +/- 2.9%, p < 0.00001, which resulted in a significant reduction of CRP
      levels (9.6 +/- 6.2 to 6.3 +/- 3.0 mg/l, p < 0.00001). Seventy-one (28.6%)
      patients reached glycemic control; however, only 29 (40.8%) of them reduced the
      CRP levels to 3 mg/l or less (1.3 +/- 1.9 mg/l), and the remaining 42 controlled
      patients maintained high CRP concentration (4.2 +/- 1.2 mg/I), p < 0.00001.
      Concentration of CRP is moderately influenced by glycemic control in the Type 2
      diabetic subjects.

PMID- 12809172
TI  - Targeting of thyroglobulin to transcytosis following megalin-mediated
      endocytosis: evidence for a preferential pH-independent pathway.
AB  - TG internalized from the colloid by megalin, bypasses the lysosomal pathway and
      is transported across thyrocytes by transcytosis. Although most of the
      intracellular mechanisms responsible for targeting of ligands to transcytosis are
      unknown, for certain ligands a role of lysosomal pH has been established. Thus,
      ligands that undergo lysosomal degradation dissociate from their receptors due to
      the low pH of endosomes, whereas certain ligands that undergo transcytosis fail
      to dissociate because they bind to their receptors at acidic pH. Here we studied
      the role of pH in TG transcytosis. We first investigated the effect of pH on
      megalin binding to TG in solid phase assays and found that, although megalin
      bound to TG at various pH values (ranging from 4-8), optimal binding was seen at
      acidic pH (ranging from 4.5-6). We then studied the effect of chloroquine (CQ)
      and ammonium chloride (AC), which increase endosomal pH, on transcytosis of TG
      across Fisher rat thyroid (FRTL-5 cells). Transcytosis assays were performed
      using FRTL-5 cells cultured on filters in dual chambered devices, with megalin
      expression only on the upper surface of the layers. TG was added to the upper
      chamber and transcytosed TG was measured in fluids collected from the lower
      chamber after incubation at 37 C. Treatment of FRTL-5 cells with CQ or AC did not
      affect binding and uptake of TG, but it did reduce T3 release from exogenously
      added TG, used as a measure of TG degradation in the lysosomal pathway. Treatment
      with CQ or AC resulted in an increase of transcytosis of TG across FRTL-5 cells,
      but only to a minimal extent (15-20%). The effects of CQ or AC and those of a
      megalin competitor (the monoclonal antibody 1H2, which reduced transcytosis) were
      not additive, suggesting that CQ and AC act on the megalin-mediated pathway. In
      conclusion, because TG binding to megalin is greatest at acidic pH, it is
      possible that TG does not dissociate from megalin in the lysosomal pathway.
      However, the pH-dependence of TG binding to megalin does not account for much of
      transcytosis, which probably occurs largely because of other mechanisms of
      targeting.

PMID- 12809173
TI  - GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's
      disease: comparison with DDAVP.
AB  - It has been shown that hexarelin stimulates ACTH and cortisol secretion in
      patients with Cushing's disease. The ACTH release induced by this peptide is 7
      fold greater than that obtained by hCRH. The mechanism of action of hexarelin on
      the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although
      controversial, there is evidence that it might be mediated by arginine
      vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol
      releasing effects of GHRP-6 in patients with Cushing's disease and to compare
      them with those obtained with DDAVP administration. We studied 10 patients with
      Cushing's disease (8 female, 2 male; age: 36.7 +/- 4.2 yr), 9 with microadenomas,
      who were submitted to both GHRP-6 (2 microg/kg iv) and DDAVP (10 micro g i.v.) in
      bolus administration on 2 separate occasions. ACTH was measured by
      immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities
      of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was
      able to increase significantly both ACTH (pmol/l, mean +/- SE; basal: 15.5 +/-
      1.7 vs peak: 45.1 +/- 9.3) and cortisol values (nmol/l, basal: 583.0 +/- 90.8 vs
      peak: 1013.4 +/- 194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(
      1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration
      there was a significant increase in ACTH (basal: 13.0 +/- 1.4 vs peak: 50.5 +/-
      16.2) and cortisol levels (basal: 572.5 +/- 112.7 vs peak: 860.5 +/- 102.8. AUC
      values for ACTH and cortisol were 1627.6 +/- 639.8 and 18364.7 +/- 5661.4,
      respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ
      significantly (peak: 45.1 +/- 9.3 vs 50.5 +/- 16.2; AUC: 1235.4 +/- 424.8 vs
      1627.6 +/- 639.8). There was a significant positive correlation between peak
      cortisol values after GHRP-6 and DDAVP administration (r = 0.87, p = 0.001). Our
      results show that GHRP-6 is able to stimulate ACTH and cortisol release in
      patients with Cushing's disease. These responses are similar to those obtained
      after DDAVP injection. These findings could suggest the hypothesis that both
      peptides act by similar mechanisms, either at hypothalamic or pituitary level.

PMID- 12809174
TI  - Early carotid atherosclerosis in normotensive severe obese premenopausal women
      with low DHEA(S).
AB  - The aim of this study was to investigate the direct involvement of
      hyperinsulinaemia, DHEA and DHEA-S [DHEA(S)] in severe obesity in early carotid
      atherosclerosis, measured as intima-media thickness (IMT). Seventeen normotensive
      premenopausal women with very high BMI (43.5 +/- 1.6 kg/m2) were recruited for
      the study. Six women were also evaluated 12 months after laparoscopic adjustable
      silicone gastric banding (LASGB). Dietary intake, fasting plasma lipid profile,
      glycemic and insulinemic response to the OGTT, adrenal secretion, at baseline and
      after ACTH stimulation test, were measured. IMT, common carotid diameter (CD) and
      left ventricular mass index (LVMi) were measured by B-mode echotomography. All
      obese subjects showed higher fasting and stimulated insulin levels, but lower
      DHEA(S) levels than controls, showing a negative correlation between both fasting
      and stimulated insulin and DHEA(S), either at baseline or after ACTH testing. IMT
      was higher (p < 0.05) than controls, with a positive correlation with stimulated
      insulin (p < 0.05) and a strong negative correlation with DHEA(S) (p < 0.001). In
      a multiple linear regression analysis, insulin response to OGTT maintained an
      association with DHEA(S) independent of fasting insulin, while DHEA maintained
      the association with IMT independent of stimulated insulin (p < 0.0001). In the
      six patients evaluated 12 months after LASGB, fasting insulin levels decreased,
      while DHEA(S) levels increased (p < 0.05). In conclusion, an early cardiovascular
      involvement was detected in this group of severe obese with hyperinsulinaemia and
      low DHEA(S), even in the absence of other well known CVD risk factors.

PMID- 12809175
TI  - Circulating ghrelin levels of visceral obese men are not modified by a short-term
      treatment with very low doses of GH replacement.
AB  - Ghrelin, the endogenous ligand for the GH secretagogue-receptor (GHS-R), in
      addition to its GH-releasing action, has orexigenic and adipogenic properties.
      These characteristics make ghrelin a potential hormone involved in the
      pathogenesis of obesity. Ghrelin levels are decreased in obese humans and it is
      unknown whether this decrease is responsible for the blunted GH secretion
      reported in visceral obesity. Since only few data are available on the potential
      feedback regulation by GH on systemic ghrelin concentrations, it remains to be
      established whether the correction of circulating GH concentrations in obese
      individuals affects ghrelin concentrations. To answer this question, we measured
      plasma ghrelin levels after a week of administration of low doses of recombinant
      human GH (rhGH) in a randomized, double-blind, placebo (PL)-controlled trial.
      This study was originally designed to evaluate the effects of GH replacement on
      lipid kinetics in visceral obese men. Six adult men with abdominal/visceral
      obesity (age 42+/-3 yr, body weight 107 +/- 10 kg, BMI 33 +/- 1 kg/m2, waist
      circumference 111 +/- 3 cm, mean +/- SE) were evaluated in the basal state (BS)
      and after one week of treatment with subcutaneous bedtime injections of either
      PL, 2.5 (GH2.5) or 3.3 (GH3.3) pg/kg/die of rhGH. In comparison to BS either PL,
      GH2.5 or GH3.3 did not significantly modify circulating ghrelin concentrations (p
      = 0.77). In contrast, a significant increase of serum GH (p = 0.0028), IGF-I (p =
      0.0033) and whole body rate of lipolysis (p = 0.038, GH2.5; p = 0.009, GH3.3)
      occurred, in comparison to BS or PL, after GH2.5 and GH3.3, without differences
      between the two treatments. These data demonstrate that in abdominal/visceral
      obese men a short-term treatment with very low doses of rhGH replacement,
      sufficient to augment the rate of lipolysis, do not modify circulating ghrelin
      levels.

PMID- 12809176
TI  - Effects of a 3-week integrated body weight reduction program on leptin levels and
      body composition in severe obese subjects.
AB  - The effects of short-term (3 weeks) integrated body weight reduction (BWR)
      program (including energy-restricted diet, aerobic and strength exercise (5
      days/week), nutritional education and psychological counseling) on plasma leptin
      levels and body composition were investigated in 54 morbidly obese patients (38
      females/16 males; mean BMI +/- SE: 41.8 +/- 0.1 kg/m2, range 35-58 kg/m2; mean
      age: 29.8 +/- 1.0 yr, age range: 18-46 yr). The BWR program induced a significant
      (p < 0.001) weight loss (BMI reduction: -4.8%) and a significant modification in
      body composition, consisting in a fat mass (FM) decrease (-7.0 +/- 0.4%, p <
      0.001) with a concomitant fat-free (FFM) mass increase (1.8 +/- 0.3%, p < 0.001).
      On average, plasma leptin levels decreased significantly both in males (from 19.4
      +/- 2.6 ng/ml to 11.6 +/- 1.3 ng/ml, p < 0.001) and in females (from 41.1 +/- 3.6
      ng/ml to 29.9 +/- 3.0 ng/ml, p < 0.001). Both before and after weight loss,
      leptin levels were positively correlated (p < 0.001) with BMI and percent fat
      mass (FM) values. Weight changes after the BWR program were negatively correlated
      with baseline leptin concentrations both in absolute terms and expressed per unit
      FM. In conclusion, a short-term diet plus aerobic/strength training effectively
      induces body composition changes and reduces plasma leptin levels. Body FM
      reduction appears to be not the unique determinant of leptin levels regulation
      and the degree of leptin over-expression may negatively affect weight loss in
      morbidly obese patients.

PMID- 12809178
TI  - Interferon-alpha-induced transient severe hypothyroidism in a patient with
      Graves' disease.
AB  - Interferons (IFNs) are proteins with anti-viral activity and are widely used in
      the treatment of patients with chronic hepatitis C virus (HCV) infection. The use
      of IFNs has resulted in thyroid dysfunction in a variety of ways. We report a
      case of a woman with hyperthyroidism due to Graves' disease who developed
      significant hypothyroidism during treatment with IFN-alpha 2a for HCV infection.
      However, after discontinuation of IFN-alpha 2a, hyperthyroidism recurred.
      Potential mechanisms by which IFNs influence thyroid function are discussed.

PMID- 12809177
TI  - Development of Graves' disease in a patient under immunosuppressive therapy after
      liver transplantation.
AB  - Susceptibility to Graves' disease (GD) is determined by multiple environmental
      and genetic factors, which are not fully understood. Because of the autoimmune
      etiology of the disease, recent reports describing the development of GD during
      long-term immunosuppressive treatment seem quite surprising. We report a second
      case of GD in a 17-yr old patient, treated with cyclosporin A and prednisone,
      after liver transplantation. The development of GD despite adequate
      immunosuppressive therapy may suggest that this patient had a genetic
      predisposition to autoimmunity and severe immunoregulatory defects. We analyzed
      the HLA-DRB1 alleles and cytotoxic T lymphocyte associated antigen-4 (CTLA-4)
      gene polymorphism (A/G) at position 49 in exon 1. The patient had the HLA-DRB1*03
      allele which is known to confer susceptibility to GD. Further studies are
      necessary to identify genes that may predispose patients specifically to GD
      during immunosuppressive therapies.

PMID- 12809179
TI  - Cow's milk and the new trials for prevention of type 1 diabetes.

PMID- 12809180
TI  - The role of the medical andrologist in the assisted reproduction era.

PMID- 12809182
TI  - Creating an environment for diversity in dental schools: one school's approach.
AB  - Recent reports have indicated the need to improve the diversity in the dental
      profession's workforce. The enrollment of underrepresented minority students in
      the nation's dental schools must increase to accomplish this goal. A complex
      change process within the dental schools is required to prepare schools to enroll
      a more diverse student body. While each dental school in the United States is
      unique, a product of its history and institutional culture, and will, therefore,
      create an environment for diversity in different ways, it is appropriate to
      describe lessons learned in individual schools as they strive for diversity. The
      purpose of this paper is to describe how one dental school, the Columbia
      University School of Dental and Oral Surgery, approached diversity, so that
      appropriate strategies can be shared among schools.

PMID- 12809183
TI  - Self-reported mental illness in a dental school clinic population.
AB  - The purpose of this study is to assess the prevalence of mental illness in a
      university-based dental clinic population. Dentists routinely review the
      patient's medical history to identify any physical disease or condition that may
      impact dental treatment. Mental illness may also affect dental treatment and
      patient management. This study examined the degree to which patients seeking
      routine dental care report these diagnoses. Data was gathered from records of 508
      consecutive new patients whose treatment plans were submitted for faculty
      approval. The patient's self-reported mental illness was obtained from the
      patient questionnaire and physical evaluation forms of the dental record. One
      hundred thirty-six patients (26.77 percent) reported at least one mental illness.
      Of all diseases and disorders recorded in the medical history, self-reported
      depression was second only to hypertension in frequency. Substance abuse,
      anxiety, anorexia, bulimia, insomnia, bipolar disorder, and post-traumatic stress
      disorder were also common findings. This study establishes the need for training
      of dental students to recognize and manage psychologically compromised patients.
      The dental curriculum must address these issues.

PMID- 12809181
TI  - Molecular heterogeneity of human GH: from basic research to clinical
      implications.

PMID- 12809184
TI  - Underserved region recruitment and return to practice: a thirty-year analysis.
AB  - The purpose of this investigation was a retrospective analysis of a select group
      of graduates from the University of Kentucky College of Dentistry (UKCD) over a
      thirty-year history to determine how many of these individuals came from the
      Appalachian Region of Eastern Kentucky, which historically has been economically
      depressed and underserved by health care practitioners including dentists. This
      same group of dental school graduates was then tracked to see if they established
      dental practices in the Appalachian region of the state. Recruiting trends were
      investigated by reviewing student records regarding county of origin from
      targeted classes at UKCD in 1969, 1979, and 1989 to gain ten-year incremental,
      historical perspectives. To identify more recent trends, classes graduating in
      1994 through 1999 were reviewed. Once identified, the databank of the Kentucky
      Board of Dentistry was used to determine if these individuals reported practicing
      in counties of Kentucky designated by the Appalachian Regional Commission (ARC).
      The findings of this study indicate an alarming decline both in numbers of
      students being recruited from this underserved area and a concomitant decline in
      those recruits returning to ARC-designated counties in the state. This study
      establishes the need for persistent diligence in recruitment of students from
      underserved areas and challenges dental schools to create strategies that will
      encourage their graduates to establish practices in these regions.

PMID- 12809185
TI  - Current status of predoctoral geriatric education in U.S. dental schools.
AB  - The elderly constitute the fastest growing segment of the U.S. population. Dental
      schools must educate dental students so that they are competent and confident in
      managing the treatment needs of elderly patients. Programs in geriatric dentistry
      have been developed in response to the changing oral health needs of growing
      numbers of older adults. The purpose of this online survey was to identify the
      current status of predoctoral geriatric dental education in U.S. dental schools.
      A questionnaire relating to the teaching of geriatric dentistry was posted on the
      World Wide Web, and fifty-four US. dental schools were invited to complete the
      form. Data from completed questionnaires were submitted to the investigators via
      email. Following repeated phone calls and emails to urge school administrators to
      respond to the electronic questionnaire, a 100 percent response rate was
      achieved. All schools reported teaching at least some aspects of geriatric
      dentistry, and 98 percent had curricula that contain required didactic material.
      Sixty-seven percent of schools reported having a clinical component to geriatric
      dental teaching. Of these schools, the clinical content was required in 77
      percent and elective in the rest. Thirty percent of schools reported a specific
      geriatric dentistry clinic within the school, and 11 percent had a remote
      clinical site. Sixty-three percent of schools have a geriatric program director
      or a chairman of a geriatric section. Over a third of schools indicated that they
      plan to extend the teaching of geriatric dentistry in the future. Geriatric
      dental education has continued to expand over the last twenty years and has
      established itself in the U.S. predoctoral dental curriculum. The format of
      teaching the subject varies considerably among the dental schools. Although
      didactic teaching of geriatric dentistry has increased markedly in the last two
      decades, clinical experience, both intramurally and extramurally, did not keep
      pace.

PMID- 12809186
TI  - Dental students' reflections on their community-based experiences: the use of
      critical incidents.
AB  - Dental schools are challenged to develop new learning methodologies and
      experiences to better prepare future dental practitioners. The purpose of this
      study was to gain insight into the community-based experiences of dental students
      as documented in their critical incident essays and explore what learning
      outcomes and benefits students reported. Following two required community-based
      clinical rotations, each student wrote a reflection essay on a self-defined
      critical incident that occurred during the rotations. Rotations took place in
      settings such as a public health clinic, special needs facility, hospital, or
      correctional institution. Essays for two classes of students were content
      analyzed for recurring themes and categories. Students were confronted in their
      rotations with a wide range of situations not typically encountered in dental
      academic settings. Their essays showed that, as a result of these rotations,
      students developed increased self-awareness, empathy, communications skills, and
      self-confidence. Critical incidents challenged assumptions and stereotypes,
      enhanced awareness of the complexities of dental care, and raised complex ethical
      dilemmas. The essays also illustrated a heightened sense of professional identity
      and enabled students to appreciate the role dentistry can play in impacting
      patients' lives. We concluded from the study that community-based dental
      education that includes a process for reflection holds promise as an educational
      strategy to facilitate the personal and professional development of future
      dentists.

PMID- 12809187
TI  - The effectiveness of computer-aided, self-instructional programs in dental
      education: a systematic review of the literature.
AB  - Computer-aided learning (CAL), self-instructional programs provide an accessible,
      interactive, and flexible way of presenting curriculum material. In order to
      assess the effectiveness of CAL programs in dental education, a systematic review
      of the published literature comparing CAL with other teaching methods was
      performed. A systematic search of the published literature was performed.
      Articles formally assessed for inclusion had to meet the following criteria:
      randomized controlled trials comparing CAL with any other method of instruction,
      and the use of academically homogeneous dental students or dental professionals
      with objective, predefined outcome criteria measuring performance, time spent,
      and attitudes. The searches located a total of 1,042 articles; of these, only
      twenty-seven articles met the inclusion criteria. Further quality assessment
      identified twelve studies that were included in the final review. Five of the
      studies documented statistically significant differences in outcome measures
      (scores on multiple choice, written or oral tests, and clinical performance)
      favoring CAL over comparison group(s), while six revealed no statistically
      significant differences. One study documented a greater improvement in test
      scores in the seminar group over the CAL group. Participants' attitudes towards
      CAL in the included studies are also discussed. Our study concluded that CAL is
      as effective as other methods of teaching and can be used as an adjunct to
      traditional education or as a means of self-instruction.

PMID- 12809188
TI  - Canadian dentists' view of the utility and accessibility of dental research.
AB  - As part of a major reorganization of health and health care research in Canada, a
      study was performed to investigate the views of Canadian dentists on the utility
      and accessibility of the results of dental research. A cross-sectional survey
      design was used. Questionnaires and a postage-prepaid reply envelope were mailed
      with the December 2001 issue of the Journal of the Canadian Dental Association
      (JCDA) to all registered Canadian dentists. No second mailing occurred. Of 17,648
      questionnaires distributed, 2,797 were returned representing a 15.8 percent
      response rate. In this sample, 64.3 percent found research findings easily
      available, 88.8 percent found research findings useful, and 95.8 percent had
      already changed one or more aspects of their clinical practice due to research
      findings. Significant differences in preferred means of learning the results of
      research and preferred formats for written reports of research findings were
      evident between generalist/clinicians and specialist/researchers. These results
      suggest that Canadian dentists are interested in the results of research and
      apply them to their practice, but that there are two main groups
      (generalist/clinicians and specialist/researchers) with different needs for
      learning the results of that research.

PMID- 12809189
TI  - Stress management for dental students performing their first pediatric
      restorative procedure.
AB  - Research has demonstrated that dental students experience considerable stress
      during their training. Students' anxiety is likely to be especially high when
      they perform their first pediatric restorative procedure. The aims of this study
      were to provide a description of dental students' level of anxiety and typical
      coping strategies and to evaluate the use of a distress management intervention
      for reducing anxiety around their first pediatric restorative procedure. Dental
      students were randomly assigned to either an Anxiety Management or an Attention
      Control group. The management group received training on relaxation strategies
      (i.e., deep breathing, progressive muscle relaxation). The control group attended
      a lecture on the relation among stress, anxiety, and health. No significant
      differences were found between group levels of anxiety related to their first
      pediatric restorative procedure. Information is provided on students' reported
      level of anxiety and general coping strategies. Limitations of the current study
      and suggestions for future research are provided.

PMID- 12809190
TI  - Genetics in dental practice: social and ethical issues surrounding genetic
      testing.
AB  - It is evident that human genetic variation is associated with many if not all
      human diseases including the more prevalent chronic diseases. As a result,
      genetics is becoming integrated into health care in all medical specialties,
      including oral medicine and its specialties. At the level of public health,
      genetic information will become increasingly important in research, policy, and
      program development. As application of genome technologies moves from the
      research laboratory to the clinical setting, a complex array of challenges will
      face dental clinicians in their efforts to use genetic information to improve
      health care and prevent disease on an individual, family, and community level.
      The broader social, ethical, and legal implications raised by the clinical use of
      genomic information have not received the same attention as did recent gene
      identification aspects of the Human Genome Project. The goal of this review is to
      foster attention and dialogue within the dental community of the ethical and
      social issues emerging from the availability of genetic information. Specific
      areas addressed include genetic testing, confidentiality, discrimination,
      informed consent, risk communication, and professional education.

PMID- 12809191
TI  - Improving the oral health status of all Americans: roles and responsibilities of
      academic dental institutions: the report of the ADEA President's Commission.
AB  - Academic dental institutions are the fundamental underpinning of the nation's
      oral health. Education, research, and patient care are the cornerstones of
      academic dentistry that form the foundation upon which the dental profession
      rises to provide care to the public. The oral health status of Americans has
      improved dramatically over the past twenty-five to thirty years. In his 2000
      report on oral health, the Surgeon General acknowledges the success of the dental
      profession in improving the oral health status of Americans over the past twenty
      five years, but he also juxtaposes this success to profound and consequential
      disparities in the oral health of Americans. In 2002, the American Dental
      Education Association brought together an ADEA President's Commission of national
      experts to explore the roles and responsibilities of academic dental institutions
      in improving the oral health status of all Americans. They have issued this
      report and made a variety of policy recommendations, including a Statement of
      Position, to the 2003 ADEA House of Delegates. The commission's work will help
      guide ADEA in such areas as: identifying barriers to oral health care, providing
      guiding principles for academic dental institutions, anticipating workforce
      needs, and improving access through a diverse workforce and the types of oral
      health providers, including full utilization of allied dental professionals and
      collaborations with colleagues from medicine.

PMID- 12809192
TI  - Measuring behaviours and perceptions: Rasch analysis as a tool for rehabilitation
      research.
AB  - Variables present in an individual, for example, independence, pain, balance,
      fatigue, depression and knowledge, cannot be measured directly (hence the term
      "latent" variables). They are usually assessed by measuring related behaviours,
      defined by sets of standardized items. The homogeneity of the different items,
      and proportionality of raw counts to measure, can only be postulated. In 1960
      Georg Rasch proposed a statistical model that complied with the fundamental
      assumptions made in measurements in physical sciences. It allowed for the
      transformation of the cumulative raw scores (achieved by a subject across items,
      or by an item across subjects) into linear continuous measures of ability (for
      subjects) and difficulty (for items). These 2 parameters, only, govern the
      probability that "pass" rather than "fail" occurs. The discrepancies between
      model-expected scores (continuous between 0 and 1) and observed scores (discrete,
      either 0 or 1) provide indexes of inconsistency of individual subjects, items and
      classes of subjects. In subsequent years the same principles were extended to
      rating scales, with items graded on more than 2 levels, and to "many-facet"
      contexts where, beyond items and subjects, multiple raters, times of
      administration, etc. converge in determining the observed scores. Rasch modelling
      has increasing application in rehabilitation medicine. New scales with
      unprecedented metric validity (including internal consistency and reliability)
      can be built. Existing scales can be improved or rejected on a sound theoretical
      basis. In clinical trials the consistency and the linearity of measures of either
      subjects or raters can be validly matched with those of physical and chemical
      measures. The stability of the item difficulties across time, cultures,
      diagnostic groups and time of administration can be estimated, thus making it
      possible to compare homogeneous measures or foster diagnostic procedures on the
      reasons for differential item functioning.

PMID- 12809193
TI  - The Northwick Park Dependency Score and its relationship to nursing hours in
      neurological rehabilitation.
AB  - OBJECTIVE: To evaluate the reliability and validity of the Northwick Park
      Dependency Score as a measure of nursing dependency. SUBJECTS: Inpatients in a
      specialist neurological rehabilitation unit. METHODS: The Northwick Park
      Dependency Score was measured by 2 assessors and compared with nursing hours. The
      Barthel ADL Index and the Short Orientation Memory and Concentration test were
      also compared with the Northwick Park Dependency Score. Time to score the Barthel
      ADL Index and Northwick Park Dependency Score was recorded. Statistical analysis
      was carried out using Spearman's Rank Correlation Coefficient. RESULTS: There was
      a high correlation between the Northwick Park Dependency Score total scores of
      the 2 observers (rho = 0.80, p < 0.005) and a correlation of rho = 0.87 between
      the Northwick Park Dependency Score total score and nursing time. There was a
      high negative correlation between the Northwick Park Dependency Score and the
      Barthel ADL Index. CONCLUSION: The Northwick Park Dependency Score is a valid and
      reliable way to assess nursing dependency. However, total scores can obscure
      relevant detail and individual raters differ. The Barthel ADL Index is equally
      related to nursing dependency.

PMID- 12809194
TI  - Societal services after traumatic spinal cord injury in Sweden.
AB  - OBJECTIVE: Societal services after traumatic spinal cord injury in Sweden were
      investigated, including self-rated levels of satisfaction with the application
      process and resource allocation. DESIGN: Survey of an incidence population.
      SUBJECTS: Thirty-four persons of a total regional incidence population (n = 48)
      with traumatic spinal cord injury. METHODS: Structured interviews using a
      standardized questionnaire. RESULTS: About 25 separate services were identified
      being available for persons with traumatic spinal cord injury. The average number
      of applications per person was 5 (range 0-11). The most common service was
      "transportation service". Of the applications, 17% were partially or totally
      rejected. Most subjects received information about available services from a
      social worker. For 13 available services at least 1 subject claimed ignorance
      about its existence. CONCLUSIONS: In Sweden, significant resources are allocated
      for allowing independence and financial compensation for individuals with
      traumatic spinal cord injury. However, this support system sometimes also results
      in frustration and disappointment. Insufficient information and co-ordination are
      reported as weaknesses. The persons' efforts to acquire knowledge of how the
      system works take time which could be better used for rehabilitation and full
      integration into the community.

PMID- 12809195
TI  - Indicators for return to work after stroke and the importance of work for
      subjective well-being and life satisfaction.
AB  - OBJECTIVES: This study focuses on the continuation of gainful employment after
      experiencing stroke, addressing factors indicative of readiness for return to
      work, subjective well-being and life satisfaction. METHODS: The target group
      comprised 120 patients, studied by means of medical records and postal
      questionnaires. RESULTS: A total of 41% had returned to work, although there were
      changes concerning employers, assignments and working hours. Individuals who had
      returned to work reported a significantly higher level in subjective well-being
      and life satisfaction. Being able to walk meant the greatest chance of returning
      to work (odds ratio = 3.98) followed by white-collar worker (odds ratio = 2.99)
      and having preserved cognitive capacity (odds ratio = 2.64). CONCLUSION:
      Returning to work after stroke is a major factor for high subjective well-being
      and life satisfaction. Three factors indicative of readiness for return to work
      were identified, providing implications for more efficient vocational
      rehabilitation programmes.

PMID- 12809196
TI  - Intensive group training versus cognitive intervention in sub-acute low back
      pain: short-term results of a single-blind randomized controlled trial.
AB  - OBJECTIVE: To evaluate the short-term effect of physical exercise and a cognitive
      intervention in low back pain. DESIGN: Randomized controlled trial. SUBJECTS:
      Ninety-three patients sick-listed for 8-12 weeks for sub-acute low back pain were
      randomized to an exercise regime (n = 30), a cognitive intervention (n = 34) or a
      control group (n = 29). METHODS: Primary outcome measures were pain, disability,
      sick-listing and satisfaction with care. Secondary outcome measures were self
      efficacy for pain and for function, fear-avoidance beliefs, emotional distress,
      generic health status and life satisfaction. RESULTS: Eighteen percent of
      subjects dropped out. Drop-out was most frequent in the exercise group. At 18
      weeks after inclusion fear-avoidance beliefs were reduced in both intervention
      groups. The cognitive group demonstrated significant improvement in disability,
      self-efficacy for pain, emotional distress, general health and life satisfaction.
      Patients in the exercise group were significantly more satisfied with the
      treatment, and patients following the exercise protocol reduced pain
      significantly. No effect on sick-listing was seen. CONCLUSION: Cognitive
      intervention improved disability and may be feasible for most patients sick
      listed in the sub-acute phase. Physical exercise reduced patients' symptoms, but
      requires high motivation by patients. Despite positive effects in intervention
      groups on variables considered as negative prognostic factors for long-term
      disability and sickness absence, interventions had no effect on sick-listing.

PMID- 12809197
TI  - Is the Rivermead Mobility Index a suitable outcome measure in lower limb
      amputees?--A psychometric validation study.
AB  - OBJECTIVE: To examine the internal consistency, validity, responsiveness and test
      scalability of the Rivermead Mobility Index. DESIGN: Methodological research
      (consecutive sampling, prospective longitudinal study). PATIENTS: 140 unilateral
      lower limb amputees (79 above-knee and 61 below-knee). METHODS: The Rivermead
      Mobility Index was administered to all patients at the beginning (T0) and at the
      end (T2) of the prosthetic training. In 70 of the patients, the Functional
      Independence Measure and a timed walking test were also carried out. RESULTS: The
      Cronbach's alpha of the Rivermead Mobility Index was 0.85 and the item-to-total
      correlation coefficients rpb ranged from 0.33 to 0.74 (p < 0.0001), for the items
      considered, at T0; 4 correlations were not calculated due to the extremely low
      variability of some item responses (mode > or = 98%). The correlation (rs) of
      Rivermead Mobility Index score with the motor subscale of the Functional
      Independence Measure was 0.83 at T0 and 0.69 at T2 (p < 0.0001, for both) and
      that with timed walking test 0.70 (p < 0.0001) at T2. The effect size was 1.35.
      The scalability coefficients were below the limits of acceptability. CONCLUSION:
      When applied in lower limb amputees, the Rivermead Mobility Index is an ordinal
      measure with adequate levels of a series of psychometric properties, which seems
      more useful for epidemiological studies than for clinical decision-making in
      single patients. Further steps should be considered to improve its item
      selection, response format and scaling properties.

PMID- 12809198
TI  - Are the ICF Activity and Participation dimensions distinct?
AB  - OBJECTIVE: To test the hypothesis that distinct Activity and Participation
      dimensions of the International Classification of Functioning, Disability, and
      Health could be identified using physical functioning items drawn from the Late
      Life Function and Disability Instrument. DESIGN: A cross-sectional, survey design
      was employed. SUBJECTS: The sample comprised 150 community-dwelling adults aged
      60 years and older. METHODS: Exploratory factor analysis was used to identify
      interpretable dimensions underlying 48 physical functioning questionnaire items.
      RESULTS: Findings revealed that one conceptual dimension underlying these
      physical functioning items was not sufficient to adequately explain the data (X2
      = 2383; p < 0.0001). A subsequent solution produced 3 distinct, interpretable
      factors that accounted for 61.1% of the variance; they were labeled: Mobility
      Activities (24.4%), Daily Activities (24.3%), and Social/Participation (12.4%).
      All 3 factors achieved high internal consistency with coefficient alphas of 0.90
      or above. CONCLUSION: Within physical functioning, distinct concepts were
      identified that conformed to the dimensions of Activity and Participation as
      proposed in the ICF. We believe this is the first empirical evidence of separate
      Activity and Participation dimensions within the International Classification of
      Functioning, Disability, and Health classification.

PMID- 12809200
TI  - From curiosities to commodities: ionic liquids begin the transition.

PMID- 12809199
TI  - Psychometric properties and practical attributes of the trunk control test in
      stroke patients.

PMID- 12809201
TI  - Molecular structure design and synthetic approaches to the heterometallic
      alkoxide complexes (soft chemistry approach to inorganic materials by the eyes of
      a crystallographer).
AB  - General principles of formation and stability of the heterometallic alkoxides
      existing due to Lewis Acid-Base interaction, isomorphous substitution and
      heterometallic metal-metal bonds are discussed. The molecular structure design
      approach based on the choice of a proper molecular structure type and completing
      it with the ligands, providing both the necessary number of donor atoms and the
      sterical protection of the metaloxygen core, is presented. Its applications in
      prediction of the composition and structure of single source precursors of
      inorganic materials are demonstrated for such classes of compounds as
      oxoalkoxides, alkoxide beta-diketonates, alkoxide carboxylates, derivatives of
      functional alcohols, metallatranes and metallasiloxanes.

PMID- 12809202
TI  - Charge assisted chiral hybrid H-bonded molecular networks.
AB  - The co-crystallisation of [Fe(CN)5NO]2- and cyclic achiral 1(2+) and chiral 2(2+)
      or 3(2+) bisamidinium tectons leads in the crystalline phase to the formation of
      1-D H-bonded achiral and chiral molecular networks respectively. In all cases,
      the network is formed by mutual bridging of the anionic and cationic units
      through a chelate mode of H-bonding.

PMID- 12809203
TI  - Luminescence-detected phase transitions in lanthanide-containing liquid crystals.
AB  - Complexes between lanthanide nitrates and a pro-mesogenic 18-membered diaza
      substituted coronand are luminescent both as powders and liquid crystals (between
      87 and 195 degrees C), and the phase transitions are detected by monitoring
      luminescence intensity and lifetime.

PMID- 12809204
TI  - A strongly positive dendrimer effect in asymmetric catalysis: allylic aminations
      with Pyrphos-palladium functionalised PPI and PAMAM dendrimers.
AB  - A remarkable and unprecedented increase in catalyst selectivity in dendrimer
      catalysis is observed for the Pyrphos-Pd catalysed allylic amination of 1,3
      diphenyl-1-acetoxypropene as a function of the dendrimer generation (with up to
      64 metal sites). This steady increase in ee-values for the allylic amination is
      less pronounced for the poly(propyleneimine)-derived catalysts than for the
      corresponding palladium-PAMAM dendrimer catalysts for which an increase in
      selectivity from 9% ee for a mononuclear reference system to 69% ee for the Pd64
      dendrimer was found.

PMID- 12809205
TI  - Coencapsulation of large and small hydrocarbons.
AB  - Combinations of small, gaseous hydrocarbons and sizable aromatics, e.g. methane
      and anthracene, are directly observed in a cylindrical capsule by NMR.

PMID- 12809206
TI  - Palladium-catalyzed, heteroatom assisted, regioselective cyclizations.
AB  - Unusual Pd-catalyzed cyclizations of unsymmetrical allylic acetates, where the
      nucleophile is tethered to the central allyl carbon, are shown for the first time
      to be remarkably controlled by heteroatom-mediated preassociation of the reacting
      partners.

PMID- 12809208
TI  - Gold nanosheets via reduction of aqueous chloroaurate ions by anthracene anions
      bound to a liquid-liquid interface.
AB  - Anthracene anions bound to a liquid-liquid interface and charged by
      photochemically reduced Keggin ions when exposed to aqueous chloroaurate ions
      result in the formation of high concentration of thin, gold nanosheets at the
      interface.

PMID- 12809207
TI  - Synthesis of HyBeacons and dual-labelled probes containing 2'-fluorescent groups
      for use in genetic analysis.
AB  - An FMOC-protected 2'-hydroxyethyl uridine phosphoramidite has been used to
      synthesise fluorescein-labelled HyBeacon probes and "FAM-ROX" dual-labelled
      fluorogenic oligonucleotides.

PMID- 12809209
TI  - Titanocene dichloride route to a tetranuclear oxo-bridged monocyclopentadienyl
      titanium(IV) calix[4]arene complex.
AB  - Lithiation of p-tBu-calix[4]arene followed by reaction with titanocene dichloride
      affords a novel tetranuclear titanium(IV) monocyclopentadienyl complex, wherein a
      single calix[4]arene in a cone conformation provides O-phenoxy coordination to
      four titanium atoms, with additional mu-oxo bridging between titanium centres in
      an eight membered ring.

PMID- 12809210
TI  - A phenolysis route to a new type of octanuclear iron(III) wheel:
      [Fe8(OH)4(OPh)8(O2CBut)12].
AB  - Alcoholysis of [Fe6O2(OH)2(O2CBut)10(hep)2] (1) affords ferric wheels of
      different nuclearities: methanol yields [Fe10(OMe)20(O2CBut)10], whereas phenol
      gives the structurally unprecedented wheel [Fe8(OH)4(OPh)8(O2CBut)12], and the
      first to contain phenoxide.

PMID- 12809211
TI  - The rate of elimination of a beta-amino zinc reagent is reduced by using a better
      leaving group.
AB  - Replacing the N-Boc-protecting group on a beta-amino organo-zinc reagent with a
      trifluoroacetyl group, which would be expected to make the nitrogen a better
      leaving group, results in a reagent that is more stable towards elimination.

PMID- 12809213
TI  - Radical anion chain process initiated by a dissociative electron transfer to a
      monocyclic endoperoxide.
AB  - Electron transfer to 3,3,6,6-tetraphenyl-1,2-dioxane results in the cleavage of
      the oxygen-oxygen bond, generating a distonic radical anion intermediate whose
      fragmentation initiates an unprecedented radical anion chain process in
      competition with a second electron transfer.

PMID- 12809212
TI  - Hydrolytic decomposition of PFCs over AlPO4-Al2O3 catalyst.
AB  - AlPO4-Al2O3 (Al/P > 9), prepared by impregnating (NH4)2HPO4 on Boehmite, showed
      high catalytic activity and durability for the hydrolytic decomposition of
      perfluoro compounds even in the presence of water and HF.

PMID- 12809214
TI  - Cooperative thermal and optical switching of spin states in a new two-dimensional
      coordination polymer.
AB  - (Fe(pmd)2[Cu(CN)2]2) (pmd = pyrimidine) displays a rigid two-dimensional
      structure and undergoes thermal- and optical-driven spin crossover behaviour;
      cooperative elastic coupling between iron(II) ions in the framework induces
      thermal hysteresis in the HS <--> LS conversion and sigmoidal HS --> LS
      relaxation of the photo-induced HS state at low temperatures.

PMID- 12809215
TI  - Ruthenium complexes carrying a disialo complex-type oligosaccharide: enzymatic
      synthesis and its application to a luminescent probe to detect influenza viruses.
AB  - Tris-bipyridine ruthenium-complexes carrying a disialo complex-type
      oligosaccharide were prepared via a one-pot transglycosylation using endo
      glycosidase (Endo M); they bind to type-A influenza viruses with excellent
      affinity (IC50 = 8.4 microM), and their luminescence intensity is strongly
      depressed by virus-binding.

PMID- 12809216
TI  - Enantioselective recognition of a chiral quaternary ammonium ion by C3 symmetric
      cyclic hexapeptides.
AB  - C3 Symmetric cyclic hexapeptides containing alternating L-proline and 3
      aminobenzoic acid derivatives as subunits possess different affinities towards
      the two enantiomers of the N,N,N-trimethyl-1-phenylethyl ammonium cation.

PMID- 12809217
TI  - A polymer supported manganese catalyst useful as a superoxide dismutase mimic.
AB  - Polymer supported manganese was synthesized via a template polymerization
      involving functional monomers to afford a catalyst with superoxide dismutase
      activity.

PMID- 12809218
TI  - An optically-active subphthalocyanine dimer.
AB  - A subphthalocyanine (SubPc) dimer linked by racemic 1,1'-binaphth-2,2'-dioxy
      (BINOL), 1, has been synthesized and characterized by 1- and 2-D 1H NMR, high
      resolution mass spectrometry (FAB), X-ray crystallography and electronic
      absorption spectroscopy. Additionally, the dimer derived from optically-active
      (R)-(+)-BINOL, 2, has been made and studied using CD and MCD spectroscopies.

PMID- 12809219
TI  - Hydrotelluration of aminoalkynes.
AB  - Metal tellurolates (M = B3+; BuTeTeBu/NaBH4/EtOH; Li3+, Te0/BuLi/THF; In3+,
      BuTeTeBu/InI/EtOH) react with aminoalkynes to produce vinylic tellurides
      containing amino groups; the regio-, and stereo-chemistry of the hydrotelluration
      reaction depend on the metallic counter ion and on the nature of the amino group
      substituent.

PMID- 12809220
TI  - An oscillating C2(2-) unit inside a copper rectangle.
AB  - [Cu4(mu-dppm)4(mu4-eta1,eta2-C[triple bond]C-)]2+ has been shown by 31P and 1H
      NMR studies to undergo two fluxional processes in solution, the oscillation of
      the C[triple bond]C2- unit inside the copper rectangle and the flipping of the
      diphosphines, and this has been supported by DFT(B3LYP) calculations.

PMID- 12809221
TI  - Surface modification of a layered alkali titanate with organosilanes.
AB  - Silylated derivatives of K2Ti4O9 x nH2O were successfully synthesized by the
      reaction of octylammonium-tetratitanate intercalation compound with n
      alkyltrimethoxysilanes.

PMID- 12809223
TI  - Preparation, X-ray structure and reactivity of a stable glycosyl iodide.
AB  - Highly selective reaction of methyl tetra-O-pivaloyl-beta-D-glucopyranuronate 2
      with iodotrimethylsilane or (Me3Si)2 and I2 affords, in excellent yield, the
      'disarmed' glycosyl iodide 1 which has good stability at 20 degrees C and
      excellent stability at 0 degrees C; the X-ray crystal structure of 1 is
      described, along with a comparison of its utility as a glycosyl donor to that of
      the corresponding bromide.

PMID- 12809222
TI  - Extra amino group-containing gramicidin S analogs possessing outer membrane
      permeabilizing activity.
AB  - Novel (2S,4R)- and (2S,4S)-4-aminoproline residue-containing analogs of the
      cyclic decapeptide antibiotic gramicidin S were synthesized, which exhibited
      marked permeabilizing activity on the outer membrane of gram-negative bacteria.

PMID- 12809224
TI  - A novel migrative addition reaction of hydrazines to the diketone derivative of
      C60.
AB  - A novel addition reaction of an aromatic hydrazine to the diketone derivative of
      C60 occurs highly regioselectively with an unusual migration of two hydrogen
      atoms from the hydrazine to the fullerene and affords a fluorescent product
      having a methylene carbon along the orifice.

PMID- 12809225
TI  - A new type of bromide anion conducting solid.
AB  - A new type of bromide anion conducting solid electrolyte was designed with the
      solid electrolyte based on oxybromide; the oxybromide lends unique
      characteristics of thermal stability and water insolubility (5.6 mg in 100 g of
      water at 25 degrees C) to the electrolyte which shows the highest Br- anion
      conductivity reported above 500 degrees C.

PMID- 12809226
TI  - Trimethyltriazacyclohexane as bridging ligand for triangular Cu3 units and C-H
      hydride abstraction into a Cu6 cluster.
AB  - Reaction of [Cu(MeCN)4](BF4) with N,N',N"-trimethyl-1,3,5-triazacyclohexane in
      CH2Cl2 leads to two Cu6 clusters containing the triazacyclohexane as a ligand to
      triangular Cu3 units with the abstraction and incorporation of chloride and
      hydride.

PMID- 12809227
TI  - The 'Trinity' helix: synthesis and structural characterisation of a C3-symmetric
      tris-bidentate ligand and its coordination to Ag(I).
AB  - The synthesis and structural characterisation of a novel C3-symmetric tris
      bidentate ligand, L, featuring a triphenylamine core appended by pyridylimine
      coordination sites is reported: 1H NMR compleximetric titration studies with
      Ag(I) and ESMS indicate the presence of [Ag3L2]3+ species in solution, consistent
      with the formation of a trinuclear double helicate complex: the Trinity helix.

PMID- 12809228
TI  - Dodecanuclear and octanuclear manganese rods.
AB  - The reaction of the neutral triangle [Mn3O(O2CR)6(L)3] with 1,1,1
      tris(hydroxymethyl)ethane (H3thme) affords novel dodecanuclear and octanuclear
      manganese complexes with unusual ladder-like cores built from edge-sharing
      triangles.

PMID- 12809230
TI  - Copper exchanged beta zeolites for the catalytic oxidation of ammonia.
AB  - Copper exchanged on beta zeolites are extremely active and selective for the
      catalytic oxidation of ammonia to nitrogen and water and this activity correlates
      to the ease of reduction of the copper species.

PMID- 12809229
TI  - Synthesis and structure of the hexameric, dodecanuclear metallamacrocycle [(5
      methyl-3-phenylpyrazole)2Zn2(OCH2CH2S)]6.
AB  - A metallamacrocycle containing twelve Zn2+ ions, making it the largest member of
      a family of pyrazole-bridged cyclic metal clusters, has been synthesized and
      structurally characterized from the reaction of [Zn(ClO4)2] with 5-methyl-3
      phenylpyrazole, 2-mercaptoethanol, and NaOH.

PMID- 12809231
TI  - Gold nanocluster confined within a cage: template-directed formation of a
      hexaporphyrin cage and its confinement capability.
AB  - A novel container complex in which a 1.4 nm gold cluster is confined within a
      hexaporphyrin cage was synthesized; the cage showed notable confinement
      capability for the cluster core, but allowed the interpenetration of small
      molecules into the interstitial space.

PMID- 12809232
TI  - A novel left-handed double helicate constructed from L-tartrate bridged
      molybdenum(vi) and gadolinium(iii) atoms.
AB  - The one-dimensional double helicate, [NH4][Mo2O4Gd(H2O)6(L-C4H2O6)2] x 4H2O (1),
      which was synthesized by the reaction of GdCl3, L-tartaric acid and ammonium
      molybdate in acidified water solution, is built up by two heft-handed single
      helical chains, linked up further by eight-coordinated GdIII pieces in an
      enantiopure left-handed double helical configuration, of which each helix is
      formed by L-tartrate bridged six-coordinated MoVI atoms.

PMID- 12809233
TI  - The influence of the Jahn-Teller effect and of heteroligands on the reactivity of
      Cu2+.
AB  - Experimentally hardly accessible Jahn-Teller inversions and the influence of
      heteroligands on the reactivity of Cu2+ are characterized by ab initio QM/MM MD
      simulations of Cu2+ ion and its amino complexes in water.

PMID- 12809234
TI  - Synthesis and structure of [(Sn(mu-PCy))3(Na x PMDETA)2], containing an electron
      deficient [(Sn(mu-PCy))3]2- dianion.
AB  - The reaction of CyPHNa with Sn(NMe2)2 in the presence of PMDETA (=
      (Me2NCH2CH2)2NMe) gives the title compound [(Sn(mu-PCy))3(Na x PMDETA)2] (1),
      containing an electron-deficient [(Sn(mu-PCy))]3(2-) dianion with a novel two
      electron, three centre (2e-3c) bonding arrangement.

PMID- 12809235
TI  - Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,2-bis(propiolyl)benzenes with
      monoalkynes leading to substituted anthraquinones.
AB  - [2 + 2 + 2] cycloadditions of 1,2-bis(propiolyl)benzenes with monoalkynes were
      effectively catalysed by Cp*RuCl(cod) under mild conditions to give substituted
      anthraquinones in moderate to high yields.

PMID- 12809236
TI  - Chemical oxidation of endohedral metallofullerenes: identification and separation
      of distinct classes.
AB  - Chemical oxidation is useful for solubilizing and separating endohedral
      metallofullerenes, as demonstrated here by a separation of three categories of
      Gd@C2n species and by the solubilization of Tm@C60+ and Tm@C70+ for the first
      time.

PMID- 12809237
TI  - Synthesis and characterization of cobalt(III) complexes containing 2
      pyridinecarboxamide ligands and their application in catalytic oxidation of
      ethylbenzene with dioxygen.
AB  - Four novel cobalt(III) complexes were found to have high catalytic activities and
      excellent selectivities in the oxidation of ethylbenzene to acetophenone using O2
      as oxidant without need of solvent.

PMID- 12809238
TI  - Improved biotransformations on charged PEGA supports.
AB  - PEGA supports functionalised with permanent charges show superior swelling
      properties in aqueous media when compared to neutral PEGA; a novel positively
      charged PEGA resin significantly improves penicillin G amidase (PGA) catalysed
      biotransformation on solid support, by favouring accessibility of the negatively
      charged enzyme.

PMID- 12809239
TI  - Visible-light induced hydrophilicity on nitrogen-substituted titanium dioxide
      films.
AB  - Nitrogen-substituted titanium dioxide thin films were found to undergo
      hydrophilic conversion under irradiation with visible light. The hydrophilicity
      was enhanced by increasing the degree of nitrogen substitution at oxygen sites.
      The water contact angle for the thin film with the greatest hydrophilicity,
      TiO1.9884N0.0116, changed from 20 degrees to 6 degrees following irradiation.

PMID- 12809240
TI  - In situ ammonia generation as a strategy for catalytic NOx reduction under oxygen
      rich conditions.
AB  - Under highly oxygen rich conditions palladium/alumina catalysts exhibit strongly
      enhanced NOx reduction activity in the presence of CO:H2 mixtures due to in situ
      generation of ammonia via the formation and subsequent hydrolysis of isocyanate
      (NCO) species.

PMID- 12809241
TI  - Synthesis of silica nanotubes from kaolin clay.
AB  - Silica nanotubes were synthesized from kaolin clay using surfactant
      intercalation, sulfuric acid and hydrothermal treatments.

PMID- 12809242
TI  - Tower-like structure of ZnO nanocolumns.
AB  - The tower-like structure of ZnO nanocolumns grows normal to alumina substrates
      via pyrolysis and oxidation of ZnS, and is formed by stacking of ZnO nanocrystals
      layer upon layer.

PMID- 12809243
TI  - 'Template-switching': a supramolecular strategy for the quantitative, gram-scale
      construction of a molecular target in the solid state.
AB  - A template-switching strategy based on the modularity of template-directed solid
      state synthesis has been successfully utilised to achieve a quantitative,
      stereospecific solid-state synthesis of a p-[2.2]-cyclophane target in gram
      quantities.

PMID- 12809244
TI  - Density functional study of the enzymatic reaction catalyzed by a cyclin
      dependent kinase.
AB  - Density functional theory (DFT) calculations were carried out to study the
      molecular mechanism of the phosphoryl transfer reaction catalyzed by cyclin
      dependent kinases (CDKs). The DFT study presented here shows that CDKs catalyze
      the phosphoryl transfer reaction from ATP to the serine substrate through a
      single step mechanism with a SN2-like transition state.

PMID- 12809245
TI  - Chiral phosphine Lewis base catalyzed asymmetric aza-Baylis-Hillman reaction of N
      sulfonated imines with methyl vinyl ketone and phenyl acrylate.
AB  - In the aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl
      ketone (MVK) promoted by chiral phosphine Lewis base: (R)-2'-diphenylphosphanyl
      [1,1']binaphthalenyl-2-ol (10 mol%), the aza-Baylis-Hillman adducts 1 were
      obtained in good yields with high ee (70-94% ee) at -30 degrees C in THF. In
      CH2Cl2 upon heating at 40 degrees C, the aza-Baylis-Hillman reaction of N
      sulfonated imines with phenyl acrylate gave the adducts 2 in high yields (60-97%)
      with moderate ee (52-77%).

PMID- 12809246
TI  - Osmylated macroporous resins: safe, highly efficient and recyclable catalysts for
      asymmetric aminohydroxylation of olefins.
AB  - Osmylated macroporous resins displayed excellent catalytic performances in the
      asymmetric aminohydroxylation of olefins and, moreover, these resins were easily
      recovered and reused without any significant decrease in catalytic efficiencies.

PMID- 12809247
TI  - Nucleophilic acylation of arylfluorides catalyzed by imidazolidenyl carbene.
AB  - Imidazolidenyl carbene catalyzes nucleophilic acylation reaction of arylfluorides
      with electron withdrawing groups to give benzophenone derivatives.

PMID- 12809248
TI  - The times, they ARE a changin'...

PMID- 12809249
TI  - Increased sympathetic nervous system activity as cause of exercise-induced
      ventricular tachycardia in patients with normal coronary arteries.
AB  - In this prospective study, we set out to determine whether analysis of heart rate
      variability (HRV) in patients with exercise-induced ventricular tachycardia
      (EIVT) and normal coronary arteries would reveal increased sympathetic nervous
      system activity. From January 1996 to December 2001, we compared 16 patients with
      EIVT and normal coronary arteries with an age- and sex-matched control group.
      Analysis of HRV showed that parameters indicative of parasympathetic activity
      were lower in our study group than in our control group: standard deviation of
      the mean of qualified NN intervals (SDNN), 81.6 +/- 14.5 vs 139.3 +/- 11.0, P
      <0.001; root mean square of successive differences (RMSSD), 22.3 +/- 4.8 vs 36.3
      +/- 6.6, P <0.001; number of NN intervals that differed by more than 5 ms from
      the adjacent interval, divided by the total number of NN intervals (PNN50), 4.8
      +/- 1.5 vs 10.2 +/- 3. 1, P <0.001; and high-frequency component (HF), 28.7 +/-
      2.5 vs 32.4 +/- 3.9, P <0.05. Conversely, parameters indicative of sympathetic
      activity were higher in patients with EIVT: low-frequency component (LF), 71.2 +/
      5.0 vs 52.0 +/- 5.8, P <0.001; and absolute low/high frequency component ratio
      (LF/HF), 2.7 +/- 0.2 vs 1.6 +/- 0.2, P <0.001. There was a positive correlation
      between EIVT and LF (r=0.79, P <0.001) and between EIVT and LF/HF (r=0.81, P
      <0.001). Our results suggest the presence of increased sympathetic and decreased
      parasympathetic tone in patients with EIVT. We conclude that EIVT is associated
      with an imbalance in the autonomic nervous system.

PMID- 12809250
TI  - Bronchogenic cyst.
AB  - The clinical presentation of the bronchogenic cyst is variable, from respiratory
      distress at birth to late appearance of symptoms. In order to determine clinical
      features and treatments, we retrospectively studied the medical records and
      pathology reports of all patients with bronchogenic cysts (n = 22) referred to
      our surgical department from February 1985 through January 2002. They included 18
      male and 4 female patients with an age range of 1 to 38 years (average, 16.4
      years). There were 14 mediastinal, 2 hilar, and 6 intrapulmonary bronchogenic
      cysts. Symptoms were present in 18 of the 22 patients. Cough was the most common
      symptom (45%). Ten patients (45%) presented with complications: severe
      hemoptysis, pneumothorax and pleuritis, esophageal compression, infected cyst,
      and postobstructive pneumonia. In all patients, complete resection of the
      bronchogenic cyst was performed by thoracotomy A postoperative sequela occurred
      in only 1 patient, who had a persistent air leak. There were no late sequelae,
      nor was there a recurrence of the cyst. The follow-up period ranged from 8 months
      to 12 years (mean, 5.2 years). Because a confident preoperative diagnosis is not
      always possible and because complications are common, we recommend surgical
      resection of all suspected bronchogenic cysts in operable candidates.

PMID- 12809251
TI  - Intravenous milrinone in treatment of advanced congestive heart failure.
AB  - Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve
      hemodynamics in patients with advanced congestive heart failure. We
      retrospectively evaluated the hemodynamic and clinical outcomes of long-term
      combination therapy with intravenous milrinone and oral beta-blockers in 65
      patients with severe congestive heart failure (New York Heart Association class
      IV function and ejection fraction <25%) refractory to oral medical therapy. Fifty
      one patients successfully began beta-blocker therapy while on intravenous
      milrinone. Oral medical therapy was maximized when possible. The mean duration of
      milrinone treatment in this combination-treatment group was 269 days (range, 14
      1,026 days). Functional class improved from IV to II-III with milrinone therapy.
      Twenty-four such patients tolerated beta-blocker up-titration and were
      successfully weaned from milrinone. Sixteen patients (31%) died while receiving
      combination therapy; one died of sudden cardiac death (on treatment day 116); the
      other 15 died of progressive heart failure or other complications. Hospital
      admissions during the previous 6 months and admissions within 6 months after
      milrinone initiation stayed the same. Meanwhile, the total number of hospital
      days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay
      decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus
      beta-blocker combination therapy is an effective treatment for heart failure even
      with beta-blocker up-titration, 2) weaning from milrinone may be possible once
      medications are maximized, 3) patients' functional status improves on the
      combination regimen, and 4) treatment-related sudden death is relatively
      infrequent during the combination regimen.

PMID- 12809252
TI  - First Turkish experience with the MicroMed DeBakey VAD.
AB  - Mechanical bridging to cardiac transplantation with a ventricular assist device
      may be a life-saving procedure for patients with end-stage heart failure. Here we
      report our 3 cases of patients implanted with the MicroMed DeBakey VAD
      (ventricular assist device). Three male patients, aged 37, 41, and 40, had end
      stage left heart failure due to idiopathic cardiomyopathy and were listed for
      cardiac transplantation. They had progressive hemodynamic deterioration. Although
      Patient 1 underwent surgery, after device implantation, for bowel necrosis caused
      by thromboemboli of unknown origin, heart transplantation was performed 70 days
      after implantation. Pump thrombosis occurred in Patient 2 on the 120th day.
      Outflow graft ligation was performed because the patient refused a pump exchange.
      This patient died on the 25th day after ligation and the 145th day after
      ventricular assist device implantation. A heparin-coated version of the device
      was implanted in Patient 3, whose preoperative profound biventricular failure had
      been improved by inotropic medication and intra-aortic balloon pump support.
      Successful heart transplantation was performed 161 days after implantation. These
      are the 1st implantations of a left ventricular assist device in Turkey. From
      these cases, we have learned that the DeBakey VAD supplies adequate blood flow
      during the bridging period and, due to its simplicity, portability, and low
      infection rate, enables discharge of the patient from the hospital. However,
      preoperative psychological evaluation and postoperative psychological support are
      important for a successful bridging procedure, as is close observation of
      coagulation and of pump operation.

PMID- 12809253
TI  - Ex vivo resuscitation of adult pig hearts.
AB  - One possible way to expand the human heart donor pool is to include non-heart
      beating human donors. To begin validating this approach, we developed an ex vivo
      cardiac perfusion circuit to support large mammalian hearts in Langendorff mode
      and beating-ejecting mode and to assess and improve their ischemic tolerance. In
      vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6
      anesthetized pigs. Hearts were isolated and connected to a recirculating
      perfusion circuit primed with autologous buffered blood (pH, 7.40). After
      retrograde aortic perfusion in Langendorff mode, the left atrium was gravity
      filled at 10-20 mmHg, and the left ventricle began to eject against a compliance
      chamber in series with a systemic reservoir set to a hydraulic afterload of 100
      120 mmHg. Left ventricular function was restored and maintained in all 6 hearts
      for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic
      pressure, left atrial pressure, and heart rate were measured. The mean myocardial
      oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and
      mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One
      resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then
      flushed with Celsior and re-resuscitated. The ex vivo perfusion method described
      herein restored left ventricular ejection function and allowed assessment of
      ischemic tolerance in large mammalian hearts, potentially a 1st step toward
      including non-heart-beating human donors in the human donor pool.

PMID- 12809254
TI  - Left common carotid artery cannulation for type A aortic dissections.
AB  - We used left common carotid artery cannulation for repair of type A aortic
      dissection in 2 patients for whom both femoral artery and axillary artery
      cannulation were thought to be more dangerous, due to dissection of the
      brachiocephalic trunk and left subclavian artery in association with abdominal
      stenosis. Before performing end-to-side anastomosis, we attached a small partial
      clamp to the left common carotid artery, thereby maintaining adequate cerebral
      blood flow during perfusion. To date, neither of our patients has experienced
      neurologic complications related to this procedure. We believe that left common
      carotid artery cannulation for type A dissections is useful when dissection of
      the brachiocephalic trunk and left subclavian artery is found in association with
      abdominal or femoral artery stenosis. To the best of our knowledge, these 2 cases
      are the 1st described in the medical literature.

PMID- 12809255
TI  - Diagnosis of pericardial disease using percutaneous biopsy: case report and
      literature review.
AB  - We describe the case of a 75-year-old man who presented with a large pericardial
      effusion and an intrapericardial mass. Malignant thymoma with pericardial
      involvement was diagnosed by percutaneous pericardial tumor biopsy. The pleural
      effusion was not malignant. The patient underwent further oncologic evaluation
      followed by adjunctive chemotherapy and radical extirpation of the tumor. He
      remains asymptomatic and free of disease 24 months after the procedure. We also
      discuss the role of percutaneous biopsy in the diagnosis of pericardial diseases.

PMID- 12809256
TI  - Large extracranial vertebral aneurysm with absent contralateral vertebral artery.
AB  - The extracranial segment of the vertebral artery is well protected, and the rate
      of occurrence of extracranial vertebral aneurysms is very low. We describe the
      case of a 40-year-old woman who presented with a large aneurysm of the left
      vertebral artery in the angiographic absence of a right vertebral artery. Her
      medical history included a motorcycle accident at the age of 20, at which time a
      neck sprain had been diagnosed. Computed tomography of the chest and neck
      revealed a 6- x 4-cm aneurysm with mural thrombus in the left thoracic outlet and
      in the first portion of the left vertebral artery before the entrance of the
      transverse foramen of the 6th cervical vertebra. Angiography of the arch vessels
      confirmed both the presence of an aneurysm of the left vertebral artery and the
      absence of a right vertebral artery. Due to the lack of contralateral vertebral
      flow, we planned to perform a graft interposition under deep hypothermic
      circulatory arrest, for cerebral protection. Unfortunately, the patient refused
      the operation and was lost to follow-up. To our knowledge, there has been no
      previous report of an extracranial vertebral artery aneurysm in the absence of a
      contralateral vertebral artery. We believe that deep hypothermic circulatory
      arrest with graft interposition is the best treatment strategy, although we did
      not, in this case, have opportunity to treat the patient.

PMID- 12809257
TI  - Pseudomonas aeruginosa pseudoaneurysm of the ascending aorta after coronary
      artery bypass graft surgery.
AB  - Mycotic pseudoaneurysms of the ascending aorta are rare in patients undergoing
      coronary artery bypass graft surgery and are usually caused by Staphylococcus
      aureus. We describe a patient with a mycotic pseudoaneurysm of the ascending
      aorta at the proximal vein graft anastomosis site after coronary artery bypass
      grafting. Cultures from the saphenous vein harvest site and from the aneurysm sac
      obtained intraoperatively during repair of the pseudoaneurysm grew Pseudomonas
      aeruginosa. Treatment included femorofemoral bypass and hypothermic circulatory
      arrest with in situ patch repair. The patient was given ceftazidime and
      gentamicin intravenously for 2 weeks, then ceftazidime alone for 6 weeks.
      Thereafter, he began taking ciprofloxacin orally for chronic suppression. He was
      doing well at 18-month follow-up.

PMID- 12809258
TI  - Right luxation of the heart after pericardial rupture caused by blunt trauma.
AB  - Rupture of the pericardium with luxation of the heart after blunt trauma is a
      fairly rare condition but carries a high mortality rate. In this report, we
      describe our experience with a case of right luxation of the heart in a young
      patient with multiple injuries due to an automobile accident. The patient, who
      was in hemodynamic failure, underwent successful emergency surgical treatment to
      replace the heart in its anatomic site. We discuss the diagnosis and management
      of this dangerous event.

PMID- 12809259
TI  - Coronary-pulmonary arteriovenous fistula used as proximal anastomotic site for
      saphenous vein grafts in patient with porcelain aorta.
AB  - Coronary artery bypass grafting in patients with porcelain aorta and calcified
      great vessels is associated with a high risk of systemic embolism. Various
      techniques have been suggested to minimize that risk. We describe the case of a
      patient with left main coronary disease and a severely calcified ascending aorta,
      who could not undergo cardiopulmonary bypass. To the best of our knowledge, this
      is the 1st reported use of a congenital coronary-pulmonary arteriovenous fistula
      as a proximal anastomotic site for saphenous vein grafts, to achieve optimal
      revascularization in a patient with porcelain aorta.

PMID- 12809260
TI  - Reoperation in a Jehovah's Witness 22 years after aortic allograft reconstruction
      of the right ventricular outflow tract.
AB  - We report the case of a 29-year-old male Jehovah's Witness who presented with
      hemolysis and right heart failure as a consequence of extreme calcification of an
      aortic valve-containing allograft and Dacron prosthesis that had been placed 22
      years earlier to repair tetralogy of Fallot. Reoperation had been denied by
      several other centers, because of the patient's refusal to undergo blood
      transfusion. For 2 weeks preoperatively, we raised the patient's hemoglobin level
      by treating him with recombinant erythropoietin, oral iron, and folic acid. At
      surgery, under normothermic cardiopulmonary bypass, we replaced the aortic
      allograft in the right ventricular outflow tract with a cryopreserved pulmonary
      allograft, also containing a valve. The postoperative course was uneventful, and
      the patient was released from the hospital on the 13th postoperative day in
      excellent condition.

PMID- 12809261
TI  - Emergent surgery for massive pulmonary embolism on the basis of clinical
      diagnosis.
AB  - We treated a 52-year-old man for a large pleural effusion that had occurred after
      he fell from a ladder. Upon discharge from the hospital, the patient collapsed
      and was nonresponsive and hypotensive. We suspected the cause to be pulmonary
      embolism. When it became evident that this patient would die without emergent
      intervention, he was taken to surgery. A massive clot was removed from the left
      pulmonary artery, and multiple smaller clots were removed from both pulmonary
      arteries. The patient recovered and was discharged from the hospital on the 11th
      postoperative day. To our knowledge, this is the 1st report of pulmonary
      embolectomy being performed on the basis of clinical diagnosis alone.

PMID- 12809262
TI  - Unruptured aneurysm of the sinus of Valsalva presenting with right ventricular
      outflow obstruction.
AB  - Sinus of Valsalva aneurysms rarely present until rupture occurs. We describe the
      case of a patient who presented with acute right heart failure and upon
      investigation was found to have an unruptured sinus of Valsalva aneurysm causing
      right ventricular outflow obstruction; there was an associated subaortic
      ventricular septal defect. To the best of our knowledge, only 1 other case with
      these features has been reported in the medical literature. The diagnosis was
      made by transthoracic echocardiography and cardiac catheterization. Through an
      aortic and right ventricular approach, we successfully excised the aneurysmal
      right coronary sinus, closed the ventricular septal defect, and replaced the
      aortic valve.

PMID- 12809263
TI  - Intestinal obstruction mimicking acute myocardial infarction.
AB  - A 64-year-old woman presented at our institution with abdominal pain. An
      electrocardiogram suggested the possibility of acute anteroseptal myocardial
      infarction. Her medical history included esophageal reconstruction with use of a
      jejunal conduit in the anterior mediastinum. Echocardiography revealed a
      distended jejunal conduit, which was compressing the right ventricle. Once the
      cause was identified, nasogastric suction was initiated and the symptoms and
      electrocardiographic changes resolved.

PMID- 12809264
TI  - Gunshot injury of the heart: an unusual cause of acute myocardial infarction.
AB  - A 30-year-old man had multiple pellet injuries after being shot. An asymptomatic,
      acute, inferior-wall myocardial infarction was detected on an electrocardiogram
      at the time of a pre-anesthetic evaluation for eye surgery. A computed
      tomographic scan of the chest confirmed the presence of an intracardiac foreign
      body. Coronary angiography showed occlusion of the distal right coronary artery
      by a pellet. The patient was managed conservatively with aspirin and metoprolol.
      In conclusion, a single coronary lesion, the absence of other cardiac
      complications, and a favorable outcome with conservative medical treatment after
      a gunshot injury contribute to the rarity of this case of myocardial infarction.

PMID- 12809265
TI  - Left ventricular pseudoaneurysm secondary to left ventricular apical venting.

PMID- 12809266
TI  - Use of myocardial biopsy catheter in retrieving "lost" intracardiac device.

PMID- 12809267
TI  - Conflict of interest.

PMID- 12809268
TI  - Upregulation of immunoreactivity of endothelin-1 and alpha-SMA in PDL
      microvasculature following acute tooth loading: an immunohistochemical study in
      the marmoset.
AB  - OBJECTIVES: To test the hypothesis that a continuous mechanical tooth load would
      elevate immunoreactivity of endothelin-1 (ET-1) and alpha-smooth muscle actin
      (alpha-SMA) in the periodontal ligament (PDL) microvasculature. DESIGN: A
      randomized control study employing 1.5 h of loading to first molars. SETTING AND
      SAMPLE POPULATION: Orthodontic Research Laboratory, Dental School, Adelaide
      University. Four young adult, male marmoset monkeys were consecutively
      anaesthetized and treated. EXPERIMENTAL VARIABLE: An external telescoping frame
      applied a jaw closing load (120-200 g) transmitted occlusally, via a rubber pad,
      to randomly assigned mandibular left or right first molars. Contralateral molars
      were used as controls. OUTCOME MEASURE: Undemineralized, midsagittal, mandibular
      molar slices, approximately 150 microm thick were immunolabelled with ET-1 and
      alpha-SMA antibodies and examined in a confocal laser scanning microscope (CLSM)
      for vascular endothelium and smooth muscle immunolabelling. RESULTS: Three
      categories of post-capillary-sized venule endothelial cell immunolabelling
      occurred: endothelium labelled solely with ET-1; endothelium labelled solely with
      alpha-SMA; endothelium labelled with both ET-1 and alpha-SMA. In endothelial
      cells, the alpha-SMA showed a moderate cytoplasmic distribution with dense
      peripheral concentration. Loading increased arteriole alpha-SMA actin labelling.
      CONCLUSION: Scattered expression of ET-1 is the default state in primate PDL
      endothelial cells. Increased antigenicity of endothelial cells to both ET-1 and
      alpha-SMA, and of arteriolar smooth muscle to alpha-SMA, is a response to shear
      and compression loads.

PMID- 12809269
TI  - Inheritance of cleft palate in South America: evidence for a major locus
      recessive.
AB  - OBJECTIVES: Determine the model of inheritance of non-syndromic cleft palate in
      humans. DESIGN: Complex segregation analysis performed in families of consecutive
      newborns affected with non-syndromic cleft palate. SETTING AND SAMPLE POPULATION:
      The Latin American Collaborative Study of Congenital Malformations (ECLAMC). Four
      hundred and seven consecutive newborns affected with non-syndromic cleft palate
      registered during the period 1967-97. OUTCOME MEASURE: Likelihood ratio test and
      Akaike information criterion (AIC) values. RESULTS: The single major locus
      recessive model provided a significantly better explanation of the data. It was
      the most parsimonious and had the smallest AIC value of the six models tested
      with approximately the same likelihood as the general model (chi2 = 2.44, p =
      0.5). CONCLUSIONS: To have defined a genetic model for non-syndromic cleft palate
      and provided evidence for a single major locus inheritance suggests that genetic
      linkage studies could be implemented.

PMID- 12809270
TI  - Effects of the headgear-activator Teuscher appliance in the treatment of Class II
      Division 1 malocclusion: a geometric morphometric study.
AB  - OBJECTIVES: To test the hypothesis that there are no gender differences in the
      outcomes of patients with class II malocclusion treated with the headgear
      activator Teuscher appliance (HATA). DESIGN: Retrospective, longitudinal SETTING
      AND SAMPLE POPULATION: Puerto Rico and Scotland, UK. Thirty-one patients
      requiring correction of class II division 1 malocclusions. EXPERIMENTAL VARIABLE:
      Male and female patients treated using HATA. OUTCOME MEASURES: Mean pre- and post
      treatment parameters derived from cephalometry subjected to t-tests, and finite
      element scaling analysis (FESA), which localizes and quantifies differences
      between mean pre- and post-treatment configurations. RESULTS: Post-treatment,
      cephalometry showed that for both males and females, angle SNA decreased, SNB
      increased, and lower facial heights increased significantly (p < 0.01). For the
      female post-treatment configuration, FESA revealed large size increases
      (approximately 20%) located in the inter-maxillary region, the ramus and
      mandibular body, and around the nasal and mental regions. Conversely, the lip
      region was diminished (approximately 20%). Similarly, male post-treatment showed
      size increases located in the inter-maxillary region that extended into the nasal
      region and the mandibular body (approximately 10-15%), and around the chin (15%).
      The lip region was diminished (approximately 5%). CONCLUSION: In the attainment
      of a normal occlusion, both male and female patients treated for class II
      malocclusions using HATA exhibit antero-posterior restraint of the maxilla,
      improvements in the mandible maintaining facial height, and lip changes
      commensurate with improvements in the soft tissue profile.

PMID- 12809271
TI  - Shear-peel bond strength of orthodontic primers in wet conditions.
AB  - OBJECTIVE: The purpose of this in vitro study was to determine whether a
      hydrophilic primer (Transbond MIP, [MIP]) produces a significant difference in
      shear/peel bond strength compared with a traditional hydrophobic primer
      (Transbond XT, [XT]) in wet (W) or dry (D) conditions and if there is a
      difference in the site of bond failure. DESIGN: A randomized blinded in vitro
      design. SETTING AND SAMPLE POPULATION: The University of Missouri-Kansas City
      School of Dentistry. Forty extracted human premolars were divided into four test
      groups (n = 10 each): MIP-dry conditions (MIPD), MIP-wet conditions (MIPW), XT
      dry (XTD) and XT-wet (XTW). EXPERIMENTAL VARIABLE: Orthodontic brackets were
      bonded to the teeth according to the manufacturer's directions except XTW and
      MIPW were exposed to moisture. OUTCOME MEASURE: Shear/peel test 24 h after
      bonding using an Instron at a crosshead speed of 0.5 mm/min and the adhesive
      remnant index to determine the site of bond failure. RESULTS: The bond strengths
      (X +/- SD) in MPa were XTD = 8.3 +/- 2.3; XTW = 0.8 +/- 0.7; MIPD = 7.5 +/- 1.8
      and MIPW = 7.9 +/- 1.7. The shear/peel bond strengths were significantly
      different: XTD = MIPD = MIPW > XTW (p < or = 0.01; two-way ANOVA; Tukey HSD). The
      ARI scores were also significantly different: XTD = MIPD = MIPW > XTW (p < or =
      0.01; Chi-square). CONCLUSIONS: Orthodontists who suspect moisture contamination
      should use a hydrophilic primer during bonding procedures to maintain shear/peel
      bond strength.

PMID- 12809272
TI  - Palatal lift prosthesis for palatopharyngeal closure in Wilson's disease.
AB  - This is a report of our work on a female patient with Wilson's disease who was
      treated for speech improvement. A palatal lift prosthesis was constructed to
      displace the soft palate superiorly and posteriorly and partially restore the
      functional deficiencies of palatopharyngeal insufficiency. Cephalometric
      radiographs confirm the association between the displacement of the soft palate
      and speech improvement.

PMID- 12809273
TI  - Cephalometric evaluation of maxillary advancement with an internal distractor in
      an adult boxer dog.
AB  - OBJECTIVE: The aim of the study was to evaluate cephalometrically the effects of
      distraction of the maxilla over a 1-year period by means of an internal
      distractor applied in a boxer dog. DESIGN: Internal distractors were placed
      bilaterally in the internal cavity of the maxillary sinus of a 2-year-old boxer
      dog after a Le Fort I osteotomy. Distraction was started 5 days after surgery and
      activations were continued for 14 days at a rate of 1 mm/day. Standardized
      lateral cephalograms were taken with an extemal source of 90 kV, 60 mS
      immediately pre-surgery, at day 1 after the start of the distraction (dp) and at
      day 5 dp, day 7 dp, day 10 dp, day 14 dp (end of distraction), at 14 days of
      consolidation period (cp), at 28 days cp and at 56 days cp (removal of the
      distractors). One year after the removal of the distractor, a final lateral
      cephalogram was taken. Cephalometric analysis was performed and superimpositions
      were used for the evaluation of the sagittal position of the maxilla. RESULTS:
      The linear measurements, as well as the superimposition showed evidence for a
      significantly advanced position of the maxilla, which was stable 1 year after
      removal of the distractor. CONCLUSION: The application of the internal maxillary
      distractor in a boxer dog resulted in a sagittal advancement of the midface that
      was still present after 1 year.

PMID- 12809274
TI  - Meta-analysis in evidence-based orthodontics.
AB  - OBJECTIVE: In the last 10 years, health sciences literature has seen a
      significant increase in papers that report findings of meta-analyses. Meta
      analysis overcomes the weakness of conventional narrative literature review.
      Moreover, it has established itself as a significant tool in clinical research
      and evidence-based medicine. But despite its station in the field, it is not
      without controversy. The aim of this paper is to present the main controversies
      that surround meta-analyses and to discuss the most important issues of conduct
      and reporting of results derived from these studies. RESULTS: Controversial
      issues include the ability of the investigators to combine studies that differ in
      important aspects; such as study populations, experimental designs and quality
      controls, and the like. It has been argued that selection bias could exist. Thus,
      it is common for the results of metaanalyses to be contradictory. As any other
      statistical procedure or analytical approach, meta-analyses too can be misused or
      abused. Misleading results could be avoided if certain basic principles are
      followed in the conduct of a meta-analysis. In particular, attention should be
      given to: (a) the methods of literature search for the studies to be included in
      the analysis, (b) the measures taken to reduce or eliminate bias, (c) the
      inclusion and exclusion criteria of the individual studies from the analysis, (d)
      how the data will be extracted from the literature, and (e) how the data will be
      analyzed statistically. CONCLUSION: Reports of meta-analytical studies carried
      out with the above parameters in mind yield a more objective appraisal of the
      evidence, and a more precise estimate of the treatment effect.

PMID- 12809275
TI  - Leaching characteristics of heavy metals from sewage sludge by Acidithiobacillus
      thiooxidans MET.
AB  - An acidophilic, sulfur-oxidizing Acidithiobacillus thiooxidans MET bacterium was
      isolated from anaerobically digested, dewatered sewage sludge. This bacterium
      showed sulfur-oxidizing ability at both acidic and neutral conditions, and
      allowed metal leaching even at a high (130 g L(-1)) sludge solids concentration.
      We found that low metal leaching efficiency at high solids concentration was
      mainly due to an increase in buffering capacity resulting in retardation of pH
      reduction. Therefore, metal leaching was mainly influenced not by sludge solids
      concentration, but by the pH (or sulfate concentration per unit sludge mass) of
      the sludge solutions. The relationship between the pH of the sludge solution and
      the efficiency of metal leaching was obtained by quantitatively investigating the
      effect of pH reduction or the amount of sulfate produced per unit sludge mass on
      leaching of each metal. Furthermore, the relationship between total metal content
      in the sludge and metal leached to the solution was obtained for each metal. Such
      a relationship allowed estimation of leachable metal at various amounts of total
      metal content in sludge.

PMID- 12809276
TI  - Three approaches to define desired soil organic matter contents.
AB  - Soil organic C is often suggested as an indicator of soil quality, but desirable
      targets are rarely specified. We tested three approaches to define maximum and
      lowest desirable soil C contents for four New Zealand soil orders. Approach 1
      used the New Zealand National Soils Database (NSD). The maximum C content was
      defined as the median value of long-term pastures, and the lower quartile defined
      the lowest desirable soil C content. Approach 2 used the CENTURY model to predict
      maximum C contents of long-term pasture. Lowest desirable content was defined by
      the level that still allowed recovery to 80% of the maximum C content over 25 yr.
      Approach 3 used an expert panel to define desirable C contents based on
      production and environmental criteria. Median C contents (0-20 cm) for the
      Recent, Granular, Melanic, and Allophanic orders were 72, 88, 98, 132 Mg ha(-1),
      and similar to contents predicted by the CENTURY model (78, 93, 102, and 134 Mg
      ha(-1), respectively). Lower quartile values (54, 78, 73, and 103 Mg ha(-1),
      respectively) were similar to the lowest desirable C contents calculated by
      CENTURY (55, 54, 67, and 104 Mg ha(-1), respectively). Expert opinion was that C
      contents could be depleted below these values with tolerable effects on
      production but less so for the environment. The CENTURY model is our preferred
      approach for setting soil organic C targets, but the model needs calibrating for
      other soils and land uses. The statistical and expert opinion approaches are less
      defensible in setting lower limits for desirable C contents.

PMID- 12809278
TI  - Iron sulfide oxidation as influenced by calcium carbonate application.
AB  - Two overburden materials, with different FeS2 contents (1.9 and 4.1%) and low
      acid neutralization potential, were limed with CaCO3 at rates of 0, 25, 50, 75,
      100, and 125% based on the amount of CaCO3 needed to provide an acid-base account
      deficit (A/Ba) of zero (A/Ba = neutralization potential--potential acidity-
      exchangeable acidity). The limed overburden materials were inoculated with
      Thiobacillus ferrooxidans and leached weekly with deionized water. Residual FeS2
      and CaCO3 were determined in samples over a 378-d period. Oxidation followed zero
      order kinetics with respect to FeS2 concentration at pH values greater than 4 and
      first-order kinetics at pH values less than 4. Zero-order oxidation rates ranged
      from 0.01 to 0.46 micromol g(-1) d(-1) in the overburden with 1.9% FeS2 and from
      0.01 to 0.22 micromol g(-1) d(-1) in the overburden with 4.1% FeS2. Oxidation
      following the first-order rate law had a first-order rate constant of 0.03 d(-1)
      in the 1.9% FeS2 overburden and 0.01 d(-1) in the 4.1% FeS2 overburden. The
      calculated half-life was 23 d for the 1.9% FeS2 overburden and 69 d for the 4.1%
      FeS2 overburden. Additions of CaCO3 affected FeS2 oxidation by controlling the pH
      of the system. Liming to greater than 50% of the acid-base account deficit did
      not significantly affect the zero-order oxidation rate. Dissolution of the
      applied CaCO3 was found to be faster than the oxidation of FeS2 at pH values
      greater than 4. It was projected that at lime rates up to 125%, the CaCO3 would
      dissolve and leach out of the system before all the FeS2 oxidized, leaving the
      potential for acid minesoil formation.

PMID- 12809277
TI  - Reduction of arsenic uptake by lettuce with ferrous sulfate applied to
      contaminated soil.
AB  - Soil contamination by arsenic (As) presents a hazard in many countries and there
      is a need for techniques to minimize As uptake by plants. A proposed in situ
      remediation method was tested by growing lettuce (Lactuca sativa L. cv. Kermit)
      in a greenhouse pot experiment on soil that contained 577 mg As kg(-1), taken
      from a former As smelter site. All combinations of iron (Fe) oxides, at
      concentrations of 0.00, 0.22, 0.54, and 1.09% (w/w), and lime, at concentrations
      of 0.00, 0.27, 0.68, and 1.36% (w/w), were tested in a factorial design. To
      create the treatments, field-moist soil, commercial-grade FeSO4, and ground
      agricultural lime were mixed and stored for one week, allowing Fe oxides to
      precipitate. Iron oxides gave highly significant (P < 0.001) reductions in
      lettuce As concentrations, down to 11% of the lettuce As concentration for
      untreated soil. For the Fe oxides and lime treatment combinations where soil pH
      was maintained nearly constant, the lettuce As concentration declined in an
      exponential relationship with increasing FeSO4 application rate and lettuce yield
      was almost unchanged. Iron oxides applied at a concentration of 1.09% did not
      give significantly lower lettuce As concentrations than the 0.54% treatment.
      Simultaneous addition of lime with FeSO4, was essential. Ferrous sulfate with
      insufficient lime lowered soil pH and caused mobilization of Al, Ba, Co, Cr, Cu,
      Fe, K, Mg, Mn, Na, Ni, Pb, Sr, and Zn. At the highest Fe oxide to lime ratios, Mn
      toxicity caused severe yield loss.

PMID- 12809279
TI  - Compost and calcium surface treatment effects on subsoil chemistry in acidic
      minespoil columns.
AB  - Surface incorporation of a liming agent in combination with compost or biosolids
      is a proven way to revegetate acidic minespoils, but little is known about the
      effect of the surface amendments on subsoil chemistry. We conducted a greenhouse
      column experiment to investigate how different surface amendments affected plant
      growth and subsoil chemistry in highly acidic minespoil material. Columns were
      filled with shale minespoil material (pH approximately 2.5), amended with CaCO3,
      CaSO4 x 2H2O (gypsum), and two rates of compost, and seeded with birdsfoot
      trefoil (Lotus corniculatus L.) and 'Kentucky 31' tall fescue (Festuca
      arundinacea Schreb.). We measured leachate and plant growth over a 170-d period
      with extensive irrigation. Without CaCO3, plants could only grow at the high
      compost rate (68.8 g kg(-1)), even though the soil pH in those treatments was
      below 3.5, indicating the capability of natural organic matter to detoxify Al(3+)
      by forming Al-organic matter complexes. Compost had no effect on the subsoil.
      When CaCO3 or gypsum was added to the surface, extractable Ca increased in the
      subsoil, but there was no relevant increase in subsoil pH. Even in the first 5 cm
      of subsoil material, extractable Al did not decrease very much, possibly because
      a jurbanite-like solid phase controlled subsoil Al(3+) activities. During the
      reclamation of highly acidic minespoil material one should therefore not expect
      significant effects of the surface treatment on the untreated subsoil. A
      sufficient root zone would have to be achieved by incorporating the liming agent
      down to the desired rooting depth.

PMID- 12809280
TI  - Nitrate distributions and source identification in the Abbotsford-Sumas Aquifer,
      northwestern Washington State.
AB  - The Abbotsford-Sumas Aquifer is a shallow, predominantly unconfined aquifer that
      spans regions in southwestern British Columbia, Canada and northwestern
      Washington, USA. The aquifer is prone to nitrate contamination because of
      extensive regional agricultural practices. A 22-month ground water nitrate
      assessment was performed in a 10-km2 study area adjacent to the international
      boundary in northwestern Washington to examine nitrate concentrations and
      nitrogen isotope ratios to characterize local source contributions from up
      gradient sources in Canada. Nitrate concentrations in excess of 10 mg nitrate as
      nitrogen per liter (mg N L(-1)) were observed in ground water from most of the 26
      domestic wells sampled in the study area, and in a creek that dissects the study
      area. The nitrate distribution was characteristic of nonpoint agricultural
      sources and consistent with the historical documentation of agriculturally
      related nitrate contamination in many parts of the aquifer. Hydrogeologic
      information, nitrogen isotope values, and statistical analyses indicated a
      nitrate concentration stratification in the study area. The highest
      concentrations (> 20 mg N L(-1)) occurred in shallow regions of the aquifer and
      were linked to local agricultural practices in northwestern Washington. Nitrate
      concentrations in excess of 10 mg N L(-1) deeper in the aquifer (> 10 m) were
      related to agricultural sources in Canada. The identification of two possible
      sources of ground water nitrate in northwestern Washington adds to the difficulty
      in assessing and implementing local nutrient management plans for protecting
      drinking water in the region.

PMID- 12809281
TI  - Use of mini-sprinklers to strip trichloroethylene and tetrachloroethylene from
      contaminated ground water.
AB  - Three low-volume mini-sprinklers were tested for their efficacy to strip
      trichloroethylene (TCE) and tetrachloroethylene (PCE) from water. Deionized water
      spiked with TCE and PCE was pumped for approximately 1 h at 0.19 to 0.21 MPa (28
      to 30 lb in(-2)) through a mini-sprinkler supported on top of a 1.8-m-tall riser.
      Water was collected in collection vessels at 0.61 and 1.22 m above the ground on
      support columns that were spaced at 0.61-m intervals from the riser base, and
      samples were composited per height and distance from the riser. Overall, air
      stripping reduced dissolved concentrations of TCE and PCE by 99.1 to 100 and 96.9
      to 100%, respectively, from mean influent dissolved concentrations of 466 to 1675
      microg L(-1) TCE and 206 to 940 microg L(-1) PCE. In terms of mass removed, the
      mini-sprinklers removed TCE and PCE at a rate of approximately 1400 to 1700 and
      700 to 900 microg L(-1), respectively, over a 1-h test period. Mini-sprinklers
      offer the advantages of (i) easy setup in series that can be used on practically
      any terrain; (ii) operation over a long period of time that does not threaten
      aquifer depletion; (iii) use in small or confined aquifers in which the capacity
      is too low to support large irrigation or purging systems; and (iv) use in
      forests in which the small, low-impact droplets of the mini-sprinklers do not
      damage bark and in which trees can help manage (via evapotranspiration) excess
      waste water.

PMID- 12809282
TI  - Virus retention and transport as influenced by different forms of soil organic
      matter.
AB  - Organic materials are widespread in natural soil and aquatic environments. Their
      effect on virus transport is very important in assessing the risk for
      contamination of ground water by viruses. This study aimed to determine how
      different forms (mineral-associated and dissolved) of natural organic matter
      influence the retention and transport of two bacteriophages (MS-2 and phiX174) in
      two porous media (a sand and a soil). We found that mineral-associated organic
      matter significantly promoted the transport of one virus (MS-2) but not the other
      (phiX174) in a phosphate-buffered saline solution. Similarly, MS-2 was retained
      less in sand columns with increasing concentrations of dissolved humic acid,
      while little effect was observed for phiX174 under the same conditions. The two
      viruses have different surface properties and thus exhibited different reactivity
      to the metal oxides present on sand particles and were affected differently by
      organic matter. Because the organic matter used in the study was negatively
      charged and hydrophilic, blocking of virus sorption sites and increasing of virus
      medium electrostatic repulsion arising from modification of the sand and virus
      surface by organic matter are probably responsible for the facilitated transport.
      For dissolved humic acid, its competition for sorption sites with viruses was an
      additional mechanism involved. This study suggests that the effect of organic
      matter varied depending on the organic material properties and the type of
      viruses involved. As a general trend, the effect of organic matter was dominated
      by electrostatic rather than hydrophobic interactions.

PMID- 12809283
TI  - A biotest for evaluating copper bioavailability to plants in a contaminated soil.
AB  - This work aimed at defining the optimal conditions for a novel ecotoxicological
      test designed for evaluating the bioavailability and phytotoxicity of metals to
      plants. This biotest, which provided easy access to roots, shoots, and
      rhizosphere soil, was applied to a vineyard calcareous soil that had been
      contaminated by the application of Cu fungicides. A preliminary hydroponic
      experiment comparing various levels of solution Cu concentration enabled us to
      determine the no observable adverse effects concentration (NOAEC), which was in
      the range 5 to 20 microM total Cu (0.01-0.06 microM free Cu ion) for rape
      (Brassica napus L. cv. Goeland). For the biotest, rape was grown in hydroponic
      conditions for 21 d in pots designed so that plants developed a planar mat of
      roots at the surface of a polyamide mesh. By then, the plants were transferred
      for 4 or 8 d onto a 1- or 3-mm-thick soil layer that was separated from the root
      mat by the mesh and connected to a reservoir of nutrient solution or deionized
      water via a filter paper wick. An 8-d period was the best option as it enabled
      plant growth to be significant. The use of 1-mm soil thickness was recommended if
      the biotest aimed at investigating root-induced changes in the rhizosphere.
      Although it may cause some artifacts, compared with deionized water, nutrient
      solution provided better standardized conditions for comparing widely differing
      soil samples. The studied soil did not induce any Cu phytotoxicity in spite of
      its fairly large total Cu content.

PMID- 12809284
TI  - Root growth and metal uptake in four grasses grown on zinc-contaminated soils.
AB  - Depth and area of rooting are important to long-term survival of plants on metal
      contaminated, steep-slope soils. We evaluated shoot and root growth and metal
      uptake of four cool-season grasses grown on a high-Zn soil in a greenhouse. A
      mixture of biosolids, fly ash, and burnt lime was placed either directly over a
      Zn-contaminated soil or over a clean, fine-grained topsoil and then the Zn
      contaminated soil; the control was the clean topsoil. The grasses were 'Reliant'
      hard fescue (Festuca brevipila R. Tracey), 'Oahe' intermediate wheatgrass
      [Elytrigia intermedia (Host) Nevski subsp. intermedia], 'Ruebens' Canada
      bluegrass (Poa compressa L.), and 'K-31' tall fescue (Festuca arundinacea
      Schreb.). Root growth in the clean soil and biosolids corresponded to the
      characteristic rooting ability of each species, while rooting into the Zn
      contaminated soil was related to the species' tolerance to Zn. While wheatgrass
      and tall fescue had the strongest root growth in the surface layers (0-5 cm) of
      clean soil or biosolids, wheatgrass roots were at least two times more dense than
      those of the other grasses in the second layer (5-27 cm) of Zn-contaminated soil.
      When grown over Zn-contaminated soil in the second layer, hard fescue (with 422
      mg/kg Zn) was the only species not to have phytotoxic levels of Zn in shoots;
      tall fescue had the highest Zn uptake (1553 mg/kg). Thus, the best long-term
      survivors in high-Zn soils should be wheatgrass, due to its ability to root
      deeply into Zn-contaminated soils, and hard fescue, with its ability to
      effectively exclude toxic Zn uptake.

PMID- 12809285
TI  - Adsorption and transport of arsenic(V) in experimental subsurface systems.
AB  - The adsorption and transport of As(V) in a heterogeneous, iron oxide-containing
      soil was investigated in batch and column laboratory experiments. The As(V)
      adsorbed rapidly to the soil over the first 48 h, but continued to adsorb slowly
      over the next several weeks, clearly indicating the potential for rate-limited
      transport. The equilibrium As(V) adsorption isotherm was markedly nonlinear,
      further indicating the potential for nonideal transport. A model developed for
      the adsorption of As(V) to hydrous ferric oxide (HFO) was able to predict the pH
      dependent adsorption of As(V) to the soil in batch experiments within 0.116 to
      0.726 root mean square error (RMSE). Arsenic(V) was significantly retarded in
      column transport experiments. The column transport experiments were modeled using
      the one-dimensional advection-dispersion equation, considering both linear and
      nonlinear adsorption equilibrium. Although the nonlinear local equilibrium model
      (NLLE, RMSE = 0.273) predicted the data better than the linear local equilibrium
      model (LLE, RMSE = 0.317), As(V) breakthrough occurred more rapidly than
      predicted by either model due to adsorption nonequilibrium. However, due to the
      presence of an irreversible or slowly desorbing fraction, the peak aqueous As(V)
      concentration (0.624 mg L(-1)) and the total amount of As(V) recovered (44%) was
      lower than predicted based on the two equilibrium models (NLLE and LLE). For the
      conditions used in this study [1 mg L(-1) As(V), pH 4.5 and 9,0-0.25 mM PO4, 0.53
      1.6 cm min(-1) pore water velocity], the effect on As(V) mobility and recovery
      increased in the order pH < pore water velocity < PO4.

PMID- 12809286
TI  - Metal bioavailability and speciation in a wetland tailings repository amended
      with biosolids compost, wood ash, and sulfate.
AB  - Lead poisoning of waterfowl from direct ingestion of wetland mine tailings has
      been reported at the Coeur d'Alene River basin in Idaho. A greenhouse study was
      conducted to evaluate the effects of surface applications of amendments on lead
      bioavailability in the tailings. Treatments included sediment only, and sediment
      with three different surface amendments: (i) biosolids compost plus wood ash,
      (ii) compost + wood ash + a low SO4(2-) addition as K2SO4, and (iii) compost +
      wood ash + a high SO4(2-) addition. Measured variables included growth and tissue
      Pb, Zn, and Cd concentration of arrowhead (Sagittaria latifolia Willd.) and
      cattail (Typha latifolia L.) and soil pH, redox potential (Eh), pore water Pb, Pb
      speciation by X-ray absorption spectroscopy, and in vitro Pb bioavailability. The
      compost + ash amendment alleviated phytotoxicity for both plant species.
      Bioavailability of Pb as measured by a rapid in vitro extract decreased by 24 to
      34% (over control) in the tailings directly below the amendment layer in the
      compost + SO4 treatments. The ratio of acid volatile sulfide (AVS) to
      simultaneously extracted metals (SEM) also indicated a reduction in Pb
      bioavailability (1:40 control, 1:20 compost, 1:8 compost + low SO4, and 1:3
      compost + high SO4). Extended X-ray adsorption fine structure (EXAFS) and X-ray
      absorption near edge structure (XANES) spectroscopy data indicated that lead
      sulfide was greater after 99 d in the treatments that included additions of
      sulfate. These results indicated that, under reducing conditions, surface
      amendments of compost + wood ash (with or without sulfate) decreased the
      bioavailability of Pb in metal-contaminated mine tailings.

PMID- 12809287
TI  - Heavy metal release from contaminated soils: comparison of column leaching and
      batch extraction results.
AB  - Heavy metals in soils may adversely affect environmental quality. In this study,
      we investigated the release of Zn, Cd, Pb, and Cu from four contaminated soils by
      column leaching and single and sequential batch extractions. Homogeneously packed
      soil columns were leached with 67 mL/g 10(-2) M CaCl2 to investigate the
      exchangeable metal pool and subsequently with 1400 mL/g 10(-2) M CaCl2 adjusted
      to pH 3 to study the potential of metal release in response to soil
      acidification. In two noncalcareous soils (pH 5.7 and 5.1), exchange by Ca
      resulted in pronounced release peaks for Zn and Cd that were coupled to the
      exchange of Mg by Ca, and 40 to 70% of total Zn and Cd contents were rapidly
      mobilized. These amounts compared well with exchangeable pools determined in
      single and sequential batch extractions. In two soils with near-neutral pH, the
      effluent concentrations of Zn and Cd were several orders of magnitude lower and
      no pronounced elution peaks were observed. This behavior was also observed for Cu
      and Pb in all four soils. When the soils were leached at pH 3, the column
      effluent patterns reflected the coupling of CaCO3 dissolution (if present) and
      other proton buffering reactions, proton-induced metal release, and metal
      specific readsorption within the soil column. Varying the flow rate by a factor
      of five had only minor effects on the release patterns. Overall, Ca exchange and
      subsequent acidification to pH 3 removed between 65 and 90% of total Zn, Cd, Pb,
      and Cu from the four contaminated soils.

PMID- 12809288
TI  - Chemical extraction methods to assess bioavailable arsenic in soil and solid
      media.
AB  - Soil ingestion by children is an important pathway in assessing public health
      risks associated with exposure to arsenic-contaminated soils. Soil chemical
      methods are available to extract various pools of soil arsenic, but their ability
      to measure bioavailable arsenic from soil ingestion is unknown. Arsenic extracted
      by five commonly used soil extractants was compared with bioavailable arsenic
      measured in vivo by immature swine (Sus scrofa) dosing trials. Fifteen
      contaminated soils that contained 233 to 17 500 mg kg(-1) arsenic were studied.
      Soil extractants were selected to dissolve surficially adsorbed and/or readily
      soluble arsenic (water, 1 M sodium acetate, 0.1 M Na2HPO4/0.1 M NaH2PO4) and
      arsenic in Fe and Mn oxide minerals (hydroxylamine hydrochloride, ammonium
      oxalate). The mean percent of total arsenic extracted was: ammonium oxalate
      (53.6%) > or = hydroxylamine hydrochloride (51.7%) > phosphate (10.5%), acetate
      (7.16%) > water (0.15%). The strongest relationship between arsenic determined by
      soil chemical extraction and in vivo bioavailable arsenic was found for
      hydroxylamine hydrochloride extractant (r = 0.88, significant at the 0.01
      probability level). Comparison of the amount of arsenic extracted by soil methods
      with bioavailable arsenic showed the following trend: ammonium oxalate,
      hydroxylamine hydrochloride > in vivo > phosphate, acetate > water. The amount of
      arsenic dissolved in the stomach (potentially bioavailable) is between
      surficially adsorbed (extracted by phosphate or acetate) and surficially adsorbed
      + nonsurficial forms in Fe and Mn oxides (extracted by hydroxylamine
      hydrochloride or ammonium oxalate). Soil extraction methods that dissolve some of
      the amorphous Fe, such as hydroxylamine hydrochloride, can be designed to provide
      closer estimates of bioavailable arsenic.

PMID- 12809289
TI  - Partitioning and availability of uranium and nickel in contaminated riparian
      sediments.
AB  - The effects of iron oxides and organic matter on the partitioning and chemical
      lability of U and Ni were examined for contaminated riparian sediments from the
      U.S. Department of Energy's Savannah River Site. In sequential extractions of
      four sediments that ranged from 12.7 to 82.2 g kg(-1) in organic carbon, U was
      found almost exclusively in moderately labile fractions (93% in acid-soluble +
      organically bound). Nickel was distributed across all operationally defined
      fractions, including substantial amounts in the very labile fractions (4-15% in
      water-soluble + exchangeable), noncrystalline and crystalline iron oxides (38
      49%), and in the nonlabile residual fraction (25-34%). Aqueous U concentrations
      in 1:1 sediment-water extracts were highly correlated to dissolved organic carbon
      (DOC) (R2 = 0.96; p < 0.0001) and ranged from 29 to 410 microg L(-1). Aqueous
      concentrations of Ni exceeded U by two to three orders of magnitude (124-2227
      microg L(-1)) but were not correlated with DOC (R2 = 0.04; p = 0.53).
      Partitioning and solubility trends suggest that Ni availability is controlled
      primarily by iron-oxide phases, whereas U availability is dominated by naturally
      occurring organic carbon. Discrete mineral phases were also identified as
      nonlabile reservoirs of anthropogenic metals. In spite of comparably high
      sediment concentrations, Ni appears to be significantly more available than U in
      riparian sediments and therefore warrants greater consideration in terms of
      environmental consequences (i.e., transport, biological uptake, and toxicity).

PMID- 12809290
TI  - Characterization of lead removal from contaminated soils by nontoxic soil-washing
      agents.
AB  - Few effective strategies exist for remediating and restoring metal-contaminated
      soils. We have evaluated the potential of two environmentally compatible,
      nondestructive, biological soil-washing agents for remediating aged, lead
      contaminated soils. Two contaminated soils were washed with 10 mM rhamnolipid
      biosurfactant and 5.3% carboxymethyl-beta-cyclodextrin (CMCD). The metal removal
      efficiency of these agents was compared with 10 mM diethylenetriamine pentaacetic
      acid (DTPA) and 10 mM KNO3. Lead removal rates by both soil-washing agents
      exceeded the removal by KNO3, but were an order of magnitude less than removal by
      the synthetic chelator, DTPA. Analysis of soil extractions revealed that the Pb
      in the first soil (3780 mg kg(-1)) was primarily associated with the soluble,
      exchangeable, oxide, and residual fractions while the Pb in the second soil (23
      900 mg kg(-1)) was found in the soluble, exchangeable, carbonate, and residual
      fractions. After 10 consecutive washes, rhamnolipid had removed 14.2 and 15.3% of
      the Pb from the first and second soils, respectively, and CMCD had removed 5 and
      13.4% from the same two soils. The Pb removal rate by both agents either
      increased or was consistent throughout the 10 extractions, indicating a potential
      for continued removal with extended washing. Significant levels of Cu and Zn in
      both soils did not prevent Pb removal by either agent. Interestingly, the
      effectiveness of each agent varied as a function of Pb speciation in the soil.
      Rhamnolipid was more effective than CMCD in removing Pb bound to amorphous iron
      oxides, while both agents demonstrated similar potential for removing soluble,
      exchangeable, and carbonate-bound Pb. Neither agent demonstrated potential for
      the complete remediation of metal-contaminated soils.

PMID- 12809291
TI  - Surface runoff losses of copper and zinc in sandy soils.
AB  - Increased anthropogenic inputs of Cu and Zn in soils have caused considerable
      concern relative to their effect on water contamination. Copper and Zn contents
      in surface soil directly influence the movement of Cu and Zn. However, minimal
      information is available on runoff losses of Cu and Zn in agricultural soils, and
      soil-extractable Cu and Zn in relation to runoff water quality. Field experiments
      were conducted in 2001 to study dissolved Cu and Zn losses in runoff in Florida
      sandy soils under commercial citrus and vegetable production and the relationship
      between soil-extractable Cu and Zn forms and dissolved Cu and Zn concentrations
      in runoff water. Five extraction methods were compared for extracting soil
      available Cu and Zn. Concentrations of dissolved Cu and Zn in runoff were
      measured and runoff discharge was monitored. Mean dissolved Cu in field runoff
      water was significantly correlated with the extractable Cu obtained only by 0.01
      mol L(-1) CaCl2, Mehlich 1, or DTPA-TEA methods. Dissolved Zn in runoff water was
      only significantly correlated with extractable Zn by 0.01 mol L(-1) CaCl2. The
      highest correlations to dissolved Cu in runoff were obtained when soil-available
      Cu was extracted by 0.01 mol L(-1) CaCl2. The results indicate that 0.01 mol L(
      1) CaCl2-extractable Cu and Zn are the best soil indexes for predicting readily
      released Cu and Zn in the sandy soils. Both runoff discharge and 0.01 mol L(-1)
      CaCl2-extractable Cu and Zn levels had significant influences on Cu and Zn loads
      in surface runoff.

PMID- 12809292
TI  - Nitrate exported in drainage waters of two sprinkler-irrigated watersheds.
AB  - Nitrate contamination of surface waters has been linked to irrigated agriculture
      across the world. We determined the NO3-N loads in the drainage waters of two
      sprinkler-irrigated watersheds located in the Ebro River basin (Spain) and their
      relationship to irrigation and N management. Crop water requirements, irrigation,
      N fertilization, and the volume and NO3-N concentration of drainage waters were
      measured or estimated during two-year (Watershed A; 494 irrigated ha) and one
      year (Watershed B; 470 irrigated ha) study periods. Maize (Zea mays L.) and
      alfalfa (Medicago sativa L.) were grown in 40 to 60% and 15 to 33% of the
      irrigated areas, respectively. The seasonal irrigation performance index (IPI)
      ranged from 92 to 100%, indicating high-quality management of irrigation.
      However, the IPI varied among fields and overirrigation occurred in 17 to 44% of
      the area. Soil and maize stalk nitrate contents measured at harvest indicated
      that N fertilizer rates could be decreased. Drainage flows were 68 mm yr(-1) in
      Watershed A and 194 mm yr(-1) in Watershed B. Drainage NO3-N concentrations were
      independent of drainage flows and similar in the irrigated and nonirrigated
      periods (average: 23-29 mg L(-1)). Drainage flows determined the exported mass of
      NO3-N, which varied from 18 (Watershed A) to 49 (Watershed B) kg ha(-1) yr(-1),
      representing 8 (Watershed A) and 22% (Watershed B) of the applied fertilizer plus
      manure N. High-quality irrigation management coupled to the split application of
      N through the sprinkler systems allowed a reasonable compromise between
      profitability and reduced N pollution in irrigation return flows.

PMID- 12809293
TI  - Effectiveness of grassed waterways in reducing runoff and sediment delivery from
      agricultural watersheds.
AB  - Grassed waterways (GWWs) drain surface runoff from fields without gullying along
      the drainageway. Secondary functions include reducing runoff volume and velocity
      and retaining sediments and harmful substances from adjacent fields. Grass cover
      (sward)-damaging sedimentation in the GWW is commonly reduced by frequent mowing,
      but in doing so the effectiveness of the waterway relative to the secondary
      functions is reduced. Our objectives were to (i) evaluate whether the maintenance
      of a GWW can be reduced if on-site erosion control is effective, (ii) measure the
      effectiveness of such a GWW, and (iii) analyze the underlying mechanisms. A long
      term (1994-2000) landscape experiment was performed in four watersheds, where two
      had GWWs for which maintenance was largely neglected. An intensive soil
      conservation system was established on all fields. Runoff and sediment delivery
      were continuously measured in the two watersheds with GWWs and in their paired
      watersheds that were similar, but without GWWs. Runoff was reduced by 90 and 10%
      for the two sets of paired watersheds, respectively. The different efficiencies
      of the GWWs resulted from different layouts (doubled width and flat-bottomed vs.
      v-shaped drainageway). The GWWs reduced sediment delivery by 97 and 77%,
      respectively, but the sward was not damaged by sedimentation. Grain sizes > 50
      microm were settled due to gravity in both GWWs. Smaller grain sizes were
      primarily settled due to infiltration, which increased with a more effective
      runoff reduction. In general, the results indicated a high potential of GWWs for
      reducing runoff volume and velocity, sediments, and agrochemicals coming from
      agricultural watersheds.

PMID- 12809294
TI  - Uptake and release of phosphorus from overland flow in a stream environment.
AB  - Phosphorus runoff from agricultural fields has been linked to fresh-water
      eutrophication. However, edge-of-field P losses can be modified by benthic
      sediments during stream flow by physiochemical processes associated with Al, Fe,
      and Ca, and by biological assimilation. We investigated fluvial P when exposed to
      stream-bed sediments (top 3 cm) collected from seven sites representing forested
      and agricultural areas (pasture and cultivated), in a mixed-land-use watershed.
      Sediment was placed in a 10-m-long, 0.2-m-wide fluvarium to a 3-cm depth and
      water was recirculated over the sediment at 2 L s(-1) and 5% slope. When overland
      flow (4 mg dissolved reactive phosphorus [DRP] and 9 mg total phosphorus [TP] L(
      1)) from manured soils was first recirculated, P uptake was associated with Al
      and Fe hydrous oxides for sediments from forested areas (pH 5.2-5.4) and by Ca
      for sediments from agricultural areas (pH 6.5-7.2). A large increase (up to 200%)
      in readily available P NH4Cl fraction was noted. After 24 h, DRP concentration in
      channel flow was related to sediment solution P concentration at which no net
      sorption or desorption of P occurs (EPC0) (r2 = 0.77), indicating quasi
      equilibrium. When fresh water (approximately 0.005 mg P L(-1) mean base flow DRP
      at seven sites) was recirculated over the sediments for 24 h, P release kinetics
      followed an exponential function. Microbial biomass P accounted for 34 to 43% of
      sediment P uptake from manure-rich overland flow. Although abiotic sediment
      processes played a dominant role in determining P uptake, biotic process are
      clearly important and both should be considered along with the location and
      management of landscape inputs for remedial strategies to be effective.

PMID- 12809295
TI  - Soil sorption of acidic pesticides: modeling pH effects.
AB  - A model of acidic pesticide sorption in soils was developed from theoretical
      modeling and experimental data, which initially considered a combination of a
      strongly acidic pesticide and a variable-charge soil with high clay content.
      Contribution of 2,4-D [(2,4-dichlorophenoxy) acetic acid] anionic-form sorption
      was small when compared with molecular sorption. Dissociation of 2,4-D was not
      sufficient to explain the variation in Kd as a function of pH. Accessibility of
      soil organic functional groups able to interact with the pesticide
      (conformational changes) as a function of organic matter dissociation was
      proposed to explain the observed differences in sorption. Experimental 2,4-D
      sorption data and K(oc) values from literature for flumetsulam [N-(2,6
      difluorophenyl)-5-methyl [1,2,4] triazolo [1,5-a] pyrimidine-2-sulfonamide] and
      sulfentrazone [N-[2,4-dichloro-5-[4-(difluromethyl)-4,5-dihydro-3-methyl-5-oxo-1H
      1,2,4-triazol-1-yl] phenyl] methanesulfonamide] in several soils fit the model.

PMID- 12809296
TI  - Stochastical analysis of surfactant-enhanced remediation of denser-than-water
      nonaqueous phase liquid (DNAPL)-contaminated soils.
AB  - Stochastical analysis was performed to assess the effect of soil spatial
      variability and heterogeneity on the recovery of denser-than-water nonaqueous
      phase liquids (DNAPL) during the process of surfactant-enhanced remediation.
      UTCHEM, a three-dimensional, multicomponent, multiphase, compositional model, was
      used to simulate water flow and chemical transport processes in heterogeneous
      soils. Soil spatial variability and heterogeneity were accounted for by
      considering the soil permeability as a spatial random variable and a
      geostatistical method was used to generate random distributions of the
      permeability. The randomly generated permeability fields were incorporated into
      UTCHEM to simulate DNAPL transport in heterogeneous media and stochastical
      analysis was conducted based on the simulated results. From the analysis, an
      exponential relationship between average DNAPL recovery and soil heterogeneity
      (defined as the standard deviation of log of permeability) was established with a
      coefficient of determination (r2) of 0.991, which indicated that DNAPL recovery
      decreased exponentially with increasing soil heterogeneity. Temporal and spatial
      distributions of relative saturations in the water phase, DNAPL, and
      microemulsion in heterogeneous soils were compared with those in homogeneous
      soils and related to soil heterogeneity. Cleanup time and uncertainty to
      determine DNAPL distributions in heterogeneous soils were also quantified. The
      study would provide useful information to design strategies for the
      characterization and remediation of nonaqueous phase liquid-contaminated soils
      with spatial variability and heterogeneity.

PMID- 12809297
TI  - Significance of anion exchange in pentachlorophenol sorption by variable-charge
      soils.
AB  - Sorption data and subsequent predictive models for evaluating acidic pesticide
      behavior on variable-charge soils are needed to improve pesticide management and
      environmental stewardship. Previous work demonstrated that sorption of
      pentachlorophenol (PCP), a model organic acid, was adequately modeled by
      accounting for pH-and pKa-dependent chemical speciation and using two organic
      carbon-normalized sorption coefficients; one each for the neutral and anionic
      species. Such models do not account for organic anion interaction to positively
      charged surface sites, which can be significant for variable-charge minerals
      present in weathered soils typical of tropical and subtropical regions. The role
      of anion exchange in sorption of ionizable chemicals by variable-charge soils was
      assessed by measuring sorption of PCP by several variable-charge soils from
      aqueous solutions of CaCl2, CaSO4, Ca(H2PO4)2 as a function of pH. Differences in
      sorption from phosphate and chloride electrolyte solutions were attributed to
      pentachlorophenolate interactions with anion exchange sites. Suppression of PCP
      sorption by phosphate ranged from negligible in a soil with essentially no
      positively charge sites, as measured by negligible anion exchange capacity, to as
      much as 69% for variable-charge soils. Pentachlorophenolate exchange correlated
      well with the ratio of pH-dependent anion exchange capacity to net surface
      charge. Sorption reversibility of PCP by both CaCl2 and Ca(H2PO4)2 solutions was
      also demonstrated. Results for PCP clearly demonstrate that sorption to anion
      exchange sites in variable-charge soils should be considered in assessing
      pesticide mobility and that phosphate fertilizer application may increase the
      mobility of acidic pesticides.

PMID- 12809298
TI  - Polycyclic aromatic hydrocarbons in mountain soils of the subtropical Atlantic.
AB  - Surface soil samples from various altitudes on Tenerife Island, ranging from sea
      level up to 3400 m above mean sea level, were analyzed to study the distribution
      of 26 polycyclic aromatic hydrocarbons (PAHs) in a remote subtropical area. The
      stable atmospheric conditions in this island define three vertically stratified
      layers: marine boundary, trade-wind inversion, and free troposphere. Total PAH
      concentrations, 1.9 to 6000 microg/kg dry wt., were high when compared with those
      in tropical areas and in a similar range to those in temperate areas. In the
      marine boundary layer, fluoranthene (Fla), pyrene (Pyr), benz [a]anthracene
      (BaA), and chrysene (C + T) were largely dominant. The predominance of Fla over
      Pyr may reflect photo-oxidative processes during atmospheric transport, although
      coal combustion inputs cannot be excluded. The PAHs found in higher concentration
      in the soils from the inversion layer were benzo[b + j]fluoranthene (BbjF) +
      benzo[k]fluoranthene (BkF) > benzo[e]pyrene (BeP) approximately indeno[1,2, 3
      cd]pyrene (Ind) > benzo[a]pyrene (BaP) approximately benzo[ghi]perylene (Bghi) >
      coronene (Cor) approximately dibenz[a,h]anthracene (Dib), reflecting that high
      temperatures and insolation prevent the accumulation of PAHs more volatile than
      BbjF in significant amounts. These climatic conditions involve a process of
      standardization that prevents the identification of specific PAH sources such as
      traffic, forest fires, or industrial inputs. Only soils with high total organic
      carbon (TOC) (e.g., 10-30%) preserve the more volatile compounds such as
      phenanthrene (Phe), methylphenanthrenes (MPhe), dimethylphenanthrenes (DMPhe),
      and retene (Ret). However, no relation between PAHs and soil TOC and black carbon
      (BC) was found. The specific PAH distributions of the free tropospheric region
      suggest a direct input from pyrolytic processes related to the volcanic emission
      of gases in Teide.

PMID- 12809299
TI  - Simplified method for detecting tritium contamination in plants and soil.
AB  - Cost-effective methods are needed to identify the presence and distribution of
      tritium near radioactive waste disposal and other contaminated sites. The
      objectives of this study were to (i) develop a simplified sample preparation
      method for determining tritium contamination in plants and (ii) determine if
      plant data could be used as an indicator of soil contamination. The method
      entailed collection and solar distillation of plant water from foliage, followed
      by filtration and adsorption of scintillation-interfering constituents on a
      graphite-based solid phase extraction (SPE) column. The method was evaluated
      using samples of creosote bush [Larrea tridentata (Sesse & Moc. ex DC.) Coville],
      an evergreen shrub, near a radioactive disposal area in the Mojave Desert.
      Laboratory tests showed that a 2-g SPE column was necessary and sufficient for
      accurate determination of known tritium concentrations in plant water.
      Comparisons of tritium concentrations in plant water determined with the solar
      distillation-SPE method and the standard (and more laborious) toluene-extraction
      method showed no significant difference between methods. Tritium concentrations
      in plant water and in water vapor of root-zone soil also showed no significant
      difference between methods. Thus, the solar distillation-SPE method provides a
      simple and cost-effective way to identify plant and soil contamination. The
      method is of sufficient accuracy to facilitate collection of plume-scale data and
      optimize placement of more sophisticated (and costly) monitoring equipment at
      contaminated sites. Although work to date has focused on one desert plant, the
      approach may be transferable to other species and environments after site
      specific experiments.

PMID- 12809300
TI  - Nitrogen removal and nitrate leaching for two perennial, sod-based forage systems
      receiving dairy effluent.
AB  - In northern Florida, year-round forage systems are used in dairy effluent
      sprayfields to reduce nitrate leaching. Our purpose was to quantify forage N
      removal and monitor nitrate N (NO3(-)-N) concentration below the rooting zone for
      two perennial, sod-based, triple-cropping systems over four 12-mo cycles (1996
      2000). The soil is an excessively drained Kershaw sand (thermic, uncoated Typic
      Quartzip-samment). Effluent N rates were 500, 690, and 910 kg ha(-1) per cycle.
      Differences in N removal between a corn (Zea mays L.)-bermudagrass (Cynodon spp.)
      rye (Secale cereale L.) system (CBR) and corn-perennial peanut (Arachis glabrata
      Benth.)-rye system (CPR) were primarily related to the performance of the
      perennial forages. Nitrogen removal of corn (125-170 kg ha(-1)) and rye (62-90 kg
      ha(-1)) was relatively stable between systems and among cycles. The greatest N
      removal was measured for CBR in the first cycle (408 kg ha(-1)), with the
      bermudagrass removing an average of 191 kg N ha(-1). In later cycles, N removal
      for bermudagrass declined because dry matter (DM) yield declined. Yield and N
      removal of perennial peanut increased over the four cycles. Nitrate N
      concentrations below the rooting zone were lower for CBR than CPR in the first
      two cycles, but differences were inconsistent in the latter two. The CBR system
      maintained low NO3(-)-N leaching in the first cycle when the bermudagrass was the
      most productive; however, it was not a sustainable system for long-term
      prevention of NO3(-)-N leaching due to declining bermudagrass yield in subsequent
      cycles. For CPR, effluent N rates > or = 500 kg ha(-1) yr(-1) have the potential
      to negatively affect ground water quality.

PMID- 12809301
TI  - Responses of red-osier dogwood to oil sands tailings treated with gypsum or alum.
AB  - The application of composite or consolidated tailings (CT) technology provides
      Alberta's oil sands industry with a means of reducing the volume of the fines
      fraction in extraction tailings and allows for faster reclamation and
      revegetation of mining sites. This study examined the effects of coagulant aids
      (gypsum and alum), used in the production of CT, on the ion content, growth, and
      survival of greenhouse-grown red-osier dogwood (Cornus sericea L. subsp.
      sericea). Seedlings were planted in gypsum-CT and alum-CT substrates, and
      compared with those planted in reclamation material (salvaged peat and till). The
      seedlings were bottom-watered with one of the following: (i) Hoagland mineral
      solution prepared in deionized water (Epstein, 1972); (ii) Hoagland solution in
      gypsum-based CT release water; or (iii) Hoagland solution in alum-based CT
      release water. Pore water of CT substrates and CT release waters had similar
      chemical characteristics, including salinity levels. However, plants in CT
      substrates had higher concentrations of ions (particularly Na and B), reduced
      growth, and higher mortality than plants in reclamation material and treated with
      CT waters. The presence of H2S indicated low-oxygen conditions in the CT
      substrates, while in the reclamation materials with CT release water treatments,
      no evidence of sulfides was observed. Low-oxygen conditions in the CT substrate
      treatments may have interfered with plant exclusion mechanisms for Na and B.
      Therefore, substrate properties may modify responses of reclamation plants to
      pore water chemistry due to the effects on oxygen availability to roots.

PMID- 12809302
TI  - Testing soils and cornstalks to evaluate nitrogen management on the watershed
      scale.
AB  - High nitrate (NO3-N) concentrations in Iowa rivers have been linked to areas of
      intensive row crop production, but they have not been experimentally linked to
      specific management practices used during row crop production. This study
      demonstrates how the late-spring test for soil NO3-N and the end-of-season test
      for cornstalk NO3-N can be used to measure N sufficiency levels across many
      fields and how the results can be used to evaluate management practices within a
      watershed. More than 3200 soil and cornstalk samples were collected over a 12-yr
      period from fields planted to corn (Zea mays L.) and already fertilized by
      farmers using their normal practices. Results showed that early-season rainfall
      and associated N losses were major factors affecting N concentrations in soils
      and cornstalks. Evidence for NO3-N movement from fields to rivers was provided by
      an inverse relationship between annual means for NO3-N concentrations in soils
      and rivers. Because these losses can be avoided by delaying N applications, the
      practice of applying N several weeks or months before plants grow was linked to
      inefficient use of fertilizer and manure N by crops. Results of the study
      demonstrate how aggregate analyses of soil and cornstalk samples collected across
      many farms and years make it possible to identify the major factors affecting N
      management outcomes and, therefore, N management practices that are likely to
      produce the best outcomes within a watershed or region. This approach seems to
      have unique potential to interrelate the management practices of farmers, the
      efficiency of N fertilization, and NO3-N concentrations in rivers.

PMID- 12809303
TI  - Herbicides and herbicide degradation products in Upper Midwest agricultural
      streams during August base-flow conditions.
AB  - Herbicide concentrations in streams of the U.S. Midwest have been shown to
      decrease through the growing season due to a variety of chemical and physical
      factors. The occurrence of herbicide degradation products at the end of the
      growing season is not well known. This study was conducted to document the
      occurrence of commonly used herbicides and their degradation products in
      Illinois, Iowa, and Minnesota streams during base-flow conditions in August 1997.
      Atrazine, the most frequently detected herbicide (94%), was present at relatively
      low concentrations (median 0.17 microg L(-1)). Metolachlor was detected in 59%
      and cyanazine in 37% of the samples. Seven of nine compounds detected in more
      than 50% of the samples were degradation products. The total concentration of the
      degradation products (median of 4.4 microg L(-1)) was significantly greater than
      the total concentration of parent compounds (median of 0.26 microg L(-1)).
      Atrazine compounds were present less frequently and in significantly smaller
      concentrations in streams draining watersheds with soils developed on less
      permeable tills than in watersheds with soils developed on more permeable loess.
      The detection and concentration of triazine compounds was negatively correlated
      with antecedent rainfall (April-July). In contrast, acetanalide compounds were
      positively correlated with antecedant rainfall in late spring and early summer
      that may transport the acetanalide degradates into ground water and subsequently
      into nearby streams. The distribution of atrazine degradation products suggests
      regional differences in atrazine degradation processes.

PMID- 12809304
TI  - Macroinvertebrate biomonitoring in intermittent coastal plain streams impacted by
      animal agriculture.
AB  - Little attention has been given to the ecology of intermittent coastal plain
      streams in the southeastern United States, and it is not known whether available
      macroinvertebrate biomonitoring methods reliably detect degradation in these
      streams. This study compared differences in biomonitoring metrics between
      reference and agricultural streams, and between the flow period (January-April)
      and the intermittent flow period (May-December). Percentages of crustaceans,
      isopods, and Ephemeroptera-Plecoptera-Trichoptera (EPT) were significantly higher
      at the reference site than the two most impacted sites during the flow period,
      probably resulting from the abundance of leaf litter and lower temperatures.
      During this same period, the agriculturally impacted sites had a significantly
      higher percentage of dipterans--a group that thrives in the silty, nutrient-rich
      waters. Four metrics (percent Crustacea, Isopoda, Diptera, and EPT) had no
      overlap between values for the most impacted and the least impacted sites during
      the flow period, but no metrics were able to detect more discrete differences
      among sites. Sites were physically and biologically similar during the
      intermittent period when natural stresses (i.e., stagnant water, high
      temperatures, low dissolved oxygen) were high, with many metrics, such as
      percentages of dominant family, burrowers, chironomids, and dipterans becoming
      similar at all sites. Our findings indicate that development of a better
      understanding of invertebrate fauna in reference conditions and of the natural
      variation in intermittent streams is necessary to develop effective biomonitoring
      programs for these systems.

PMID- 12809305
TI  - Phosphorus loss to runoff water twenty-four hours after application of liquid
      swine manure or fertilizer.
AB  - Phosphorus (P) added to soil from fertilizer or manure application could pose a
      threat to water quality due to its role in eutrophication of fresh water
      resources. Incorporating such amendments into the soil is an established best
      management practice (BMP) for reducing soluble P losses in runoff water, but
      could also lead to higher erosion. The objective of this study was to test
      whether incorporation of manure or fertilizer 24 h before an intense rain could
      also reduce sediment-bound and total phosphorus (TP) losses in runoff. A rainfall
      simulation study was conducted on field plots (sandy loam with 6-7% slope, little
      surface residue, recently cultivated) that received two application rates of
      liquid swine manure or liquid ammonium polyphosphate fertilizer, using either
      surface-broadcast or incorporated methods of application. Incorporation increased
      the total suspended solids (TSS) concentrations in runoff but mass losses were
      not affected. Incorporation also reduced flow-weighted concentrations and losses
      of dissolved reactive phosphorus (DRP) and TP by as much as 30 to 60% depending
      on source (fertilizer vs. manure) and application rate. Phosphorus is moved below
      the mixing zone of interaction on incorporation, and thus the effect of the
      amount and availability of P in this zone is more important than cultivation on
      subsequent P losses in runoff. Incorporating manure or fertilizer in areas of
      intense erosive rain, recent extensive tillage, and with little or no surface
      residue is therefore a best management practice that should be adhered to in
      order to minimize contamination of surface water. Results also show comparatively
      lower P losses from manure than fertilizer.

PMID- 12809306
TI  - Effects of prolonged irrigation with treated municipal effluent on runoff rate.
AB  - The use of domestic effluents for the irrigation of crops has been widespread in
      Israel for the past 30 years. The sodium adsorption ratio (SAR) of the
      standardized domestic effluents ranges between 4 and 6. According to the
      literature, when soils with SAR levels of 4 to 6 are exposed to direct raindrop
      impact they are subjected to enhanced aggregate disintegration, leading to
      sealing processes of the soil surface and subsequent increased runoff and soil
      erosion. However, these phenomena were not observed in the laboratory and field
      experiments of this study. On the other hand, a rapid decrease of the soil SAR to
      its initial values was observed, in laboratory and fieldwork, once the soil was
      subjected to a simulated rainstorm of distilled water (laboratory) or natural
      rainstorms (field plots). We can conclude that the process of SAR increase during
      irrigation with standardized effluent water is reversible. Further investigation
      in this direction can lead to recommendations regarding the necessary levels of
      domestic sewage water purification in correlation with soil types, climatic
      conditions, and hazards to tap water aquifers.

PMID- 12809307
TI  - Retention and runoff losses of atrazine and metribuzin in soil.
AB  - Minimizing herbicide runoff and mobility in the soil and thus potential
      contamination of water resources is a national concern. Metribuzin [4-amino-6
      (1,1-dimethylethyl)-3-(methylthio)-1,2,4-triazin-5(4H)-one] and atrazine [2
      chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine] dynamics in surface soils
      and in runoff waters were studied on six 0.2-ha sugarcane (Saccharum spp.) plots
      of a Commerce silt loam (fine-silty, mixed, superactive, nonacid, thermic
      Fluvaquentic Endoaquept) during three growing seasons under different best
      management practices. Metribuzin was applied in the spring as a postemergence
      herbicide and atrazine was applied following winter harvest. Both herbicides were
      applied on top of the sugarcane rows as 0.6- or 0.9-m band width application, or
      broadcast application, where the entire area was treated. Maximum effluent
      concentrations were measured from the broadcast treatment and ranged from 600 to
      1100 microg L(-1) for atrazine and 250 to 450 microg L(-1) for metribuzin.
      Atrazine runoff losses were highest for the broadcast treatment (2.8-11% of that
      applied) and lowest for the 0.6-m band treatment (1.9-7.6%), with a similar trend
      for metribuzin losses. Measured extractable herbicides from the surface soil
      exhibited a sharp decrease with time and were well described with a simple first
      order decay model. For atrazine, estimates for the decay rate (lambda) were
      higher than for metribuzin. Results based on laboratory adsorption-desorption
      (kinetic-batch) measurements were consistent with field observations. The
      distribution coefficients (Kd) for atrazine exhibited stronger retention over
      time in comparison with metribuzin on the Commerce soil. Moreover, discrepancies
      between adsorption isotherm and desorption indicated slower release and that
      hysteresis was more pronounced for atrazine compared with metribuzin.

PMID- 12809308
TI  - Effect of broadcast manure on runoff phosphorus concentrations over successive
      rainfall events.
AB  - Concern over eutrophication has directed attention to manure management effects
      on phosphorus (P) loss in runoff. This study evaluates the effects of manure
      application rate and type on runoff P concentrations from two, acidic
      agricultural soils over successive runoff events. Soils were packed into 100- x
      20- x 5-cm runoff boxes and broadcast with three manures (dairy, Bos taurus,
      layer poultry, Gallus gallus; swine, Sus scrofa) at six rates, from 0 to 150 kg
      total phosphorus (TP) ha(-1). Simulated rainfall (70 mm h(-1)) was applied until
      30 min of runoff was collected 3, 10, and 24 d after manure application.
      Application rate was related to runoff P (r2 = 0.50-0.98), due to increased
      concentrations of dissolved reactive phosphorus (DRP) in runoff; as application
      rate increased, so did the contribution of DRP to runoff TP. Varied
      concentrations of water-extractable phosphorus (WEP) in manures (2-8 g WEP kg(
      1)) resulted in significantly lower DRP concentrations in runoff from dairy
      manure treatments (0.4-2.2 mg DRP L(-1)) than from poultry (0.3-32.5 mg DRP L(
      1)) and swine manure treatments (0.3-22.7 mg DRP L(-1)). Differences in runoff
      DRP concentrations related to manure type and application rate were diminished by
      repeated rainfall events, probably as a result of manure P translocation into the
      soil and removal of applied P by runoff. Differential erosion of broadcast manure
      caused significant differences in runoff TP concentrations between soils. Results
      highlight the important, but transient, role of soluble P in manure on runoff P,
      and point to the interactive effects of management and soils on runoff P losses.

PMID- 12809309
TI  - Estimating soil phosphorus requirements and limits from oxalate extract data.
AB  - Excessive fertilizer and manure phosphorus (P) inputs to soils elevates P in soil
      solution and surface runoff, which can lead to freshwater eutrophication. Runoff
      P can be related to soil test P and P sorption saturation, but these approaches
      are restricted to a limited range of soil types or are difficult to determine on
      a routine basis. The purpose of this study was to determine whether easily
      measurable soil characteristics were related to the soil phosphorus requirements
      (P(req), the amount of P sorbed at a particular solution P level). The P(req) was
      determined for 18 chemically diverse soils from sorption isotherm data (corrected
      for native sorbed P) and was found to be highly correlated to the sum of oxalate
      extractable Al and Fe (R2 > 0.90). Native sorbed P, also determined from oxalate
      extraction, was subtracted from the P(req) to determine soil phosphorus limits
      (PL, the amount of P that can be added to soil to reach P(req)). Using this
      approach, the PL to reach 0.2 mg P L(-1) in solution ranged between -92 and 253
      mg P kg(-1). Negative values identified soils with surplus P, while positive
      values showed soils with P deficiency. The results showed that P, Al, and Fe in
      oxalate extracts of soils held promise for determining PL to reach up to 10 mg P
      L(-1) in solution (leading to potential runoff from many soils). The soil oxalate
      extraction test could be integrated into existing best management practices for
      improving soil fertility and protecting water quality.

PMID- 12809310
TI  - Studies on mobility and degradation pathways of terbuthylazine using lysimeters
      on a field scale.
AB  - Terbuthylazine [N2-tert-butyl-6-chloro-N4-ethyl-1,3,5-triazine-2,4-diamine]
      degradation pathways in agricultural soils were evaluated by following the
      appearance and mobility of its main transformation products: dealkylated and
      hydroxylated derivatives. Three experimental degradation studies in open field
      were performed in different hydraulic conditions: constant hydraulic head on
      topsoil, achieved to simulate the highest-risk situation for the aquifer,
      intermittent artificial precipitation to simulate a medium-risk situation; and
      natural precipitation to reproduce the lowest-risk condition. Concentrations of
      terbuthylazine transformation products derived from dealkylation and
      hydroxylation reactions were measured in leachates and soil samples collected
      during the three experiments. Desethylterbuthylazine (DET) and
      deethylterbuthylazine-2-hydroxide [DETH; 4-amino-6-terbutylamino-(1,3,5)-triazine
      2-OH] were found to be the highest-leaching compounds and therefore can be
      considered as potential pollutants for aquifer contamination.

PMID- 12809311
TI  - Reduction of ammonia emission by shallow slurry injection: injection efficiency
      and additional energy demand.
AB  - Ammonia (NH3) emission from livestock production causes undesirable environmental
      effects and a loss of plant-available nitrogen. Much atmospheric NH3 is lost from
      livestock manure applied in the field. The NH3 emission may be reduced by slurry
      injection, but slurry injection in general, and especially on grassland,
      increases the energy demand and places heavy demands on the slurry injection
      techniques used. The reduction in NH3 emission, injection efficiency, and energy
      demand of six different shallow slurry-injection techniques was examined. The NH3
      emission from cattle slurry applied to grassland was reduced by all the injectors
      tested in the study, but there were major differences in the NH3 reduction
      potential of the different types of injectors. Compared with the trailing hose
      spreading technique, the NH3 loss was reduced by 75% when cattle slurry was
      injected using the most efficient slurry injection technique, and by 20% when
      incorporated by the least efficient injection technique. The reduction in NH3
      emission was correlated with injection depth and the volume of the slot created.
      The additional energy demand for reducing ammonia emissions by slurry injection
      was approximately 13 000 kJ ha(-1) for a 20% reduction and 34 000 kJ ha(-1) for a
      75% reduction. The additional energy demand corresponds to additional emissions
      of, respectively, 5.6 and 14.5 kg CO2 per ha injected.

PMID- 12809312
TI  - Weed seed viability in composted beef cattle feedlot manure.
AB  - Manure composting has gained increased acceptance by the beef cattle (Bos taurus)
      feedlot industry in southern Alberta, Canada. Unlike fresh manure, compost is
      often promoted as being "weed-free." Studies were conducted with five weed
      species in 1997 and thirteen in 1999 to examine the effect of feedlot manure
      composting on weed seed viability. Weed seeds were buried in open-air compost
      windrows and recovered at various times during the thermophilic phase of
      composting. Windrow temperature and water contents were also measured.
      Germinability was zero for all composted weed seeds at all sampling times in
      1997. However, some seeds remained viable (positive tetrazolium test denoting
      respiration) on Day 70. In 1999, only one of the thirteen species retained
      germinability on Day 21 and only two species had respiring seeds on Day 42. Time
      viability relationships during composting were defined by exponential decay
      models. Lethal temperatures to eliminate viability was species-dependent. In
      1999, four weed species were killed in the initial 7 d of composting at a lethal
      temperature of 39 degrees C while temperatures of > 60 degrees C were required
      for two species. Regression analysis on weed seed viability versus windrow
      temperature resulted in significant R2 values, which showed that only 17 to 29%
      of the variation in viability was accounted for by temperature. The lack of
      definitive relationships between temperature and weed seed viability demonstrated
      that factors other than temperature may play a role in eliminating weed seeds
      during composting.

PMID- 12809313
TI  - Phosphorus sorption and availability in soils amended with animal manures and
      sewage sludge.
AB  - Soils that receive large applications of animal wastes and sewage sludge are
      vulnerable to releasing environmentally significant concentrations of dissolved P
      available to subsurface flow owing to the gradual saturation of the soil's P
      sorption capacity. This study evaluated P sorption (calculated from Langmuir
      isotherms) and availability of P (as CaCl2-P and resin P) in soils incubated for
      20 d with poultry litter, poultry manure, cattle slurry, municipal sewage sludge,
      or KH2PO4, added on a P-equivalent basis (100 mg P kg(-1)). All the P sources had
      a marked negative effect on P sorption and a positive effect on P availability in
      all soils. In the cattle slurry- and KH2PO4-treated soils, the decreases in P
      sorption maximum (19-66%) and binding energy (25-89%) were consistently larger
      than the corresponding decreases (7-41% and 11-30%) in poultry litter-, poultry
      manure-, and sewage sludge-treated soils. The effects of cattle slurry and KH2PO4
      on P availability were, in most cases, larger than those of the other P sources.
      In the poultry litter, poultry manure, and sewage sludge treatments, the increase
      in soil solution P was inversely related (R2 = 0.75) to the input of Ca from
      these relatively high Ca (13.5-42 g kg(-1)) sources. Correlation analyses implied
      that the magnitude of the changes in P sorption and availability was not related
      to the water-extractable P content of the P sources. Future research on the
      sustainable application of organic wastes to agricultural soils needs to consider
      the non-P- as well as P-containing components of the waste.

PMID- 12809314
TI  - Sequestration of phosphorus by acid mine drainage floc.
AB  - Solubilization and transport of phosphorus (P) to the water environment is a
      critical environmental issue. Flocs resulting from neutralizing acid mine
      drainage (AMD) were tested as a possible low-cost amendment to reduce the loss of
      soluble P from agricultural fields and animal wastewater. Flocs were prepared by
      neutralizing natural and synthetic solutions of AMD with limestone, lime,
      ammonium hydroxide, and sodium hydroxide. Phosphorus sequestration was tested in
      three distinct environments: water, soil, and manure storage basins. In water,
      flocs prepared from AMD adsorbed 10 to 20 g P kg(-1) dry floc in equilibrium with
      1 mg L(-1) soluble P. Similar results were observed for both Fe-based and Al
      based synthetic flocs. A local soil sample adsorbed about 0.1 g P kg(-1), about
      two orders of magnitude less. The AMD-derived flocs were mixed with a high-P soil
      at 5 to 80 g floc kg(-1) soil, followed by water and acid (Mehlich-1)
      extractions. All flocs performed similarly. About 70% of the water-extractable P
      was sequestered by the floc when applied at a rate of 20 g floc kg(-1) soil,
      whereas plant-available P only decreased by about 30%. Under anaerobic conditions
      simulating manure storage basins, all AMD flocs reduced soluble P by greater than
      95% at a rate of 0.2 g floc g(-1) rainbow trout (Oncorhynchus mykiss) manure.
      These findings indicate that AMD flocs could be an effective agent for preventing
      soluble P losses from soil and manure to the water environment, while at the same
      time decreasing the costs associated with AMD treatment.

PMID- 12809315
TI  - Sediment retention in rangeland riparian buffers.
AB  - Controlling nonpoint-source sediment pollution is a common goal of riparian
      management, but there is little quantitative information about factors affecting
      performance of rangeland riparian buffers. This study evaluated the influence of
      vegetation characteristics, buffer width, slope, and stubble height on sediment
      retention in a Montana foothills meadow. Three vegetation types (sedge wetland,
      rush transition, bunchgrass upland) were compared using twenty-six 6- x 2-m plots
      spanning 2 to 20% slopes. Plots were clipped moderately (10-15 cm stubble) or
      severely (2-5 cm stubble). Sediment (silt + fine sand) was added to simulated
      overland runoff 6, 2, or 1 m above the bottom of each plot. Runoff was sampled at
      15-s to > 5-min intervals until sediment concentrations approached background
      levels. Sediment retention was affected strongly by buffer width and moderately
      by vegetation type and slope, but was not affected by stubble height. Mean
      sediment retention ranged from 63 to > 99% for different combinations of buffer
      width and vegetation type, with 94 to 99% retention in 6-m-wide buffers
      regardless of vegetation type or slope. Results suggest that rangeland riparian
      buffers should be at least 6 m wide, with dense vegetation, to be effective and
      reliable. Narrower widths, steep slopes, and sparse vegetation increase risk of
      sediment delivery to streams. Vegetation characteristics such as biomass, cover,
      or density are more appropriate than stubble height for judging capacity to
      remove sediment from overland runoff, though stubble height may indirectly
      indicate livestock impacts that can affect buffer performance.

PMID- 12809316
TI  - Estimating turf pesticide volatilization from simple evapotranspiration models.
AB  - A previously developed model by Haith et al. (2002) related pesticide
      volatilization from turf to evapotranspiration (ET) by scaling factors determined
      from vapor pressures and heats of vaporization. Although the model provided
      volatilization estimates that compared well with field measurements, it relied on
      the Penman ET equation, requiring hourly temperature, wind speed, and solar
      radiation data, none of which are routinely available at field sites. The current
      study determined that the volatilization model works equally well with a simpler
      ET equation requiring only daily temperatures. Three daily temperature-based ET
      models were evaluated as vehicles for estimating pesticide volatilization from
      turf: Hamon, Hargreaves-Samani, and a modified Priestley-Taylor. When compared
      with field volatilization measurements for eight pesticides, volatilization
      estimates produced from the Hargreaves-Samani model most closely approximated
      both the field observations and the previous estimates based on the more data
      intensive Penman model. Mean estimated volatilization exceeded mean observations
      by 15% and the coefficient of variation (R2) between estimates and observations
      was 0.65. The comparable values based on Penman ET were 17% and 0.63,
      respectively.

PMID- 12809317
TI  - Denitrification potential in urban riparian zones.
AB  - Denitrification, the anaerobic microbial conversion of nitrate (NO3-) to nitrogen
      (N) gases, is an important process contributing to the ability of riparian zones
      to function as "sinks" for NO3- in watersheds. There has been little analysis of
      riparian zones in urban watersheds despite concerns about high NO3-
      concentrations in many urban streams. Vegetation and soils in urban ecosystems
      are often highly disturbed, and few studies have examined microbial processes
      like denitrification in these ecosystems. In this study, we measured
      denitrification potential and a suite of related microbial parameters (microbial
      biomass carbon [C] and N content, potential net N mineralization and
      nitrification, soil inorganic N pools) in four rural and four urban riparian
      zones in the Baltimore, MD metropolitan area. Two of the riparian zones were
      forested and two had herbaceous vegetation in each land use context. There were
      few differences between urban and rural and herbaceous and forest riparian zones,
      but variability was much higher in urban than rural sites. There were strong
      positive relationships between soil moisture and organic matter content and
      denitrification potential. Given the importance of surface runoff in urban
      watersheds, the high denitrification potential of the surface soils that we
      observed suggests that if surface runoff can be channeled through areas with high
      denitrification potential (e.g., stormwater detention basins with wetland
      vegetation), these areas could function as important NO3- sinks in urban
      watersheds.

PMID- 12809318
TI  - Rationing decisions and individual responsibility for illness: are all lives
      equal?
AB  - OBJECTIVES: This survey measured individuals' rationing allocation choices for
      situations in which patients are deemed to hold personal responsibility for their
      diseases and the influence of different arguments on such choices. METHODS: The
      association between allocation decisions for liver disease and asthma and the
      belief that a patient was responsible for his or her illness was modeled using
      multivariable regression analysis, controlling for the effect of arguments on
      choices. RESULTS: In data from 310 returned surveys (43% response rate),
      respondents were 10 to 17 times more likely to allocate liver transplants or
      asthma treatment to patients they deemed not responsible for their illnesses than
      to patients they deemed responsible for their conditions (liver transplants: odds
      ratio [OR] = 10.3, 95% confidence interval ([CI] = 2.5-42.1; asthma: OR = 16.8,
      95% CI = 2.1-136.6). CONCLUSIONS: Personal responsibility for illness was an
      important consideration in respondents' rationing allocation decisions. These
      choices appeared to be stable although possibly influenced by respondents'
      interpretations of the survey scenarios and decision tasks.

PMID- 12809319
TI  - "Perfect health" versus "disease free": the impact of anchor point choice on the
      measurement of preferences and the calculation of disease-specific disutilities.
AB  - BACKGROUND: During preference testing, some investigators use "perfect health" as
      the upper anchor point of their measurement scale ("Q scale"), whereas others use
      "disease free" ("q scale"), which can confound the interpretation and comparison
      of study results. METHODS: We measured current health preferences among 74
      patients with cervical spondylotic myelopathy (CSM) on both the Q and q scales
      using the visual analogue scale (VAS), standard gamble (SG), time tradeoff (TTO),
      and willingness to pay (WTP). RESULTS: There were significant differences in mean
      Q and q scale values for the VAS, SG, and WTP (for all, P < 0.011); there were no
      significant differences for mean TTO values (P = 0.592). CSM accounted for 63% to
      82% of total disutility, whereas other comorbidities accounted for 28% to 37%.
      CONCLUSIONS: Preferences for CSM differ when measured on the Q and q scales.
      Caution should be used when comparing and interpreting health values measured on
      scales with different upper anchors.

PMID- 12809320
TI  - Unexplained complaints in general practice: prevalence, patients' expectations,
      and professionals' test-ordering behavior.
AB  - OBJECTIVE: To gain insight into general practitioners' (GPs) test-ordering
      behavior for patients presenting with unexplained complaints. An unexplained
      complaint's symptoms are not alarming, and there is no plausible medical or
      psychosocial explanation for it. The Dutch College of General Practitioners
      (DCGP) recommends a watchful, waiting attitude for test ordering for unexplained
      complaints. METHODS: Observational, cross-sectional study of 567 doctor-patient
      consultations performed by 21 GPs. RESULTS: On average, 13% of consultations
      involved complaints considered unexplained by GPs. Unexplained complaints were
      positively related to test ordering (adjusted odds ratio [OR] = 2.4, 95%
      confidence interval [CI] 1.1-5.3), despite the DCGP's recommendation. Patients'
      expectations about testing influenced test ordering even more (adjusted OR = 4.1,
      95% CI 2.2-7.6). DISCUSSION: Unexplained complaints happen daily in general
      practice. Besides the DCGP's recommendation, factors such as GPs' desire to
      understand complaints and patients' expectations seem to have impacts. Guideline
      development and quality improvement projects should respect, next to Bayesian
      rules, GP- and patient-related determinants of test ordering.

PMID- 12809321
TI  - A potential error in evaluating cancer screening: a comparison of 2 approaches
      for modeling underlying disease progression.
AB  - BACKGROUND: Evaluating cancer screening often requires modeling the underlying
      disease process and not observed disease, particularly in the absence of direct
      evidence linking screening to a survival benefit. METHODS: To illustrate a
      potential error in modeling disease progression among healthy persons with a
      history of a precancerous lesion, we constructed 2 models with 4 basic health
      states (disease free, presence of a precancerous lesion, presence of cancer,
      dead), calibrated to predict the same 10-year cancer incidence. We assumed a
      homogeneous cohort enters each model free of disease, the probability of
      developing a precancerous lesion was greater for patients with a history of a
      prior lesion, and the screening test was perfect and riskless. In one model, we
      assigned a higher transition probability from a precancerous lesion to cancer in
      those with a history of a previously removed lesion; in the other, we assumed it
      was equal to those with no history. RESULTS: Using the 1st model, life expectancy
      without screening was 2.4 months longer than with screening. This error did not
      occur using the 2nd model, in which the transition from precancerous lesions to
      cancer was not conditional on a history of a lesion. This modeling error's
      magnitude was examined under a variety of assumptions. CONCLUSIONS: We have
      identified an important error to avoid when modeling the underlying disease
      process in evaluating screening programs for cancers associated with precancerous
      states.

PMID- 12809322
TI  - Properties of the cumulative risk-adjusted mortality (CRAM) chart, including the
      number of deaths before a doubling of the death rate is detected.
AB  - The cumulative risk-adjusted mortality (CRAM) chart is intended to detect changes
      in the failure rate in a sequence of trials when the relative risk but not the
      absolute risk of failure at each trial is known. For example, surgical mortality
      can be monitored taking into account the heterogeneity of patients and
      procedures. We simulate abrupt change to twice or half the previous failure rate
      and series with no change. As with any control procedure, changes are eventually
      signaled whether or not real changes have occurred. With initial mean failure
      rates ranging from 1% to 25%, the median number of failures before a doubling is
      signaled is about 20 (i.e., about 10 extra failures) and is nearly independent of
      the extent of heterogeneity in the series. CRAM chart calculations give an
      estimate of the risk of failure at the next trial, and we document the
      performance of this estimate.

PMID- 12809323
TI  - A Bayesian approach to aid in formulary decision making: incorporating
      institution-specific cost-effectiveness data with clinical trial results.
AB  - Pharmacy and therapeutics committees commonly cite a lack of generalizability as
      a reason for not incorporating cost-effectiveness information into decision
      making. To address this concern, many committees undertake site-specific economic
      evaluations, which are often limited by small sample sizes and nonrandomized
      designs. We show how 2 complementary approaches were used to minimize these
      limitations in an economic evaluation of abciximab at 1 institution. Using a
      propensity score methodology, we selected patients who did not receive abciximab
      for the comparison cohort. Then, we adopted a Bayesian, hierarchical, random
      effects model to integrate site-specific and clinical trial data. We applied the
      posterior distributions of effectiveness with local cost data in a traditional
      decision-analytic model. In 74% of the simulations, abciximab was cost-effective
      at 1 institution at the $50,000 per life year saved threshold, assuming a 50:50
      split of patients undergoing coronary stenting and angioplasty. Among patients
      undergoing coronary stenting, the cost-effectiveness ratio of the addition of
      abciximab was at or below the $50,000 per life year saved threshold in 66.0% of
      the simulations.

PMID- 12809324
TI  - Neonatal hearing screening.
AB  - Neonatal hearing screening can be performed using reliable and reproducible
      methods. Intervention before the age of 6 months with hearing aids and
      appropriate educational support services will give the infant the best possible
      opportunity to develop language. Potential barriers to efficient implementation
      of a neonatal hearing screening program include access to appropriate and timely
      diagnostic and support services and insurance to cover the services. Without
      universal neonatal hearing screening, many children with hearing loss will be
      missed, which will have a direct negative impact on their speech, language,
      educational, and social development.

PMID- 12809325
TI  - Genetic screening for deafness.
AB  - Genetic testing for deafness has become a reality. It has changed the paradigm
      for evaluating deaf and hard-of-hearing persons and will be used by physicians
      for diagnostic purposes and as a basis for treatment and management options.
      Although mutation screening is currently available for only a limited number of
      genes, in these specific instances, diagnosis, carrier detection, and
      reproductive risk counseling can be provided. In the coming years there will be
      an expansion of the role of genetic testing and counseling will not be limited to
      reproductive issues. Treatment and management decisions will be made based on
      specific genetic diagnoses. Although genetic testing may be a confusing service
      for the practicing otolaryngologist, it is an important part of medical care. New
      discoveries and technologies will expand and increase the complexity of genetic
      testing options and it will become the responsibility of otolaryngologists to
      familiarize themselves with current discoveries and accepted protocols for
      genetic testing.

PMID- 12809326
TI  - Auditory neuropathy/dyssynchrony: its diagnosis and management.
AB  - Patients with auditory neuropathy/dyssynchrony exhibit no auditory brain stem
      response (ABR), no middle ear muscle response, and both normal otoacoustic
      emissions or normal cochlear microphonics. An absent or grossly abnormal ABR is
      not always associated with deafness. In contrast, a hearing loss of 30 dB or more
      usually predicts absent otoacoustic emissions, but normal emissions can be seen
      in some patients whose behavioral audiograms imply total deafness. This article
      reviews the underlying physiology that makes these tests both useful and
      potentially misleading, and recommends steps to be considered by primary care
      physicians and other professionals to compensate for the vulnerabilities of each
      of the procedures.

PMID- 12809327
TI  - Cochlear implantation update.
AB  - Cochlear implantation is recognized as a valuable intervention with important
      implications for the acquisition of speech perception and verbal language in
      children with severe to profound hearing impairment. Auditory rehabilitation,
      language intervention, and close coordination between parents, schools, and the
      implant center are necessary to maximize efficacy. Early identification of
      hearing loss, early hearing aid use and language intervention, and cochlear
      implantation by 2 years of age are positive predictors for language acquisition
      that can approach the levels of normal-hearing children. There are early
      indications that increased access to mainstream education and gains in quality of
      life are long-term benefits that render cochlear implantation a cost-effective
      intervention.

PMID- 12809328
TI  - Disorders of phonation in children.
AB  - Vocal disturbances in children are surprisingly common. Typical pathologic
      conditions differ, however, from those that are seen commonly in adults.
      Disturbances in the vibratory characteristic of the vocal folds cause dysphonia.
      The most common causes for dysphonia are infectious, anatomic, congenital,
      inflammatory, neoplastic, neurologic, or iatrogenic in nature. A child who
      presents with hoarseness demands a rapid and thorough assessment. Fine points
      during the history may provide the clinician with clues as to the correct
      etiologic category. Proper treatment requires an accurate diagnosis. Although
      some conditions are similar in the adult larynx, treatment of the pediatric
      larynx often differs. An understanding of the changing and growing pediatric
      larynx is necessary for treatment and satisfactory results.

PMID- 12809329
TI  - Ankyloglossia: does it matter?
AB  - Ankyloglossia is an uncommon oral anomaly that can cause difficulty with breast
      feeding, speech articulation, and mechanical tasks such as licking the lips and
      kissing. For many years the subject of ankyloglossia has been controversial, with
      practitioners of many specialties having widely different views regarding its
      significance. In many children, ankyloglossia is asymptomatic; the condition may
      resolve spontaneously, or affected children may learn to compensate adequately
      for their decreased lingual mobility. Some children, however, benefit from
      surgical intervention (frenotomy or frenuloplasty) for their tongue-tie. Parents
      should be educated about the possible long-term effects of tongue-tie while their
      child is young (< 1 year of age), so that they may make an informed choice
      regarding possible therapy.

PMID- 12809330
TI  - Modern management of acute otitis media.
AB  - Although recent clinical trials suggest that conjugate vaccination will be less
      effective for the prevention of AOM than for IPD, these trials have demonstrated
      impressive reductions in the incidence of AOM due to invasive and antibiotic
      resistant pneumococcal serotypes. These data suggest that if serotype replacement
      does occur in immunized children, the causative agents are likely to be less
      virulent than vaccine strains. Furthermore, a recent cost-effectiveness analysis
      projected that immunization of healthy infants with the heptavalent conjugate
      vaccine could prevent over one million episodes of AOM and 12,000 cases of
      invasive pneumococcal disease. Because significant reductions have been
      demonstrated in the incidence of frequently recurrent AOM, children with the
      worst disease stand to benefit most from vaccination. Based on data currently
      available, however, the conjugate vaccine is not going to eradicate AOM.
      Consequently, there will continue to be a need to scrutinize the threshold for
      prescribing antibiotics. In addition, there will be an ongoing need for surgery
      in some cases of recurrent AOM and persistent OME.

PMID- 12809331
TI  - Treatment of pediatric sinusitis.
AB  - The successful management of RS in children relies on careful diagnosis,
      recognition of causative factors, and judicious yet adequate antibiotic usage.
      Refractory cases will require surgical therapy, with adenoidectomy as the first
      line intervention and ESS reserved for those cases refractory to adenoidectomy.
      This overall approach will improve quality of life and prevent complications in
      children with RS.

PMID- 12809332
TI  - Obstructive sleep apnea in children: an update.
AB  - The diagnosis of obstructive sleep apnea in children requires clinical suspicion
      supplemented with the use of specific diagnostic tests. Polysomnography remains
      the key to diagnosis, and helps to assess the need for treatment, the risk for
      perioperative respiratory compromise, and the likelihood of persistent OSAS after
      treatment. Adenotonsillectomy is the mainstay of treatment, although children
      with complex medical conditions that affect upper airway anatomy and tone may
      require additional treatment.

PMID- 12809333
TI  - Infectious indications for tonsillectomy.
AB  - Tonsillectomy is the most common major surgery performed on children in the
      United States. Recurrent throat infections of either bacterial or viral etiology
      can cause significant morbidity and decreased quality of life, and potentially
      lead to life-threatening complications. When performed in the proper patient,
      tonsillectomy can be a highly effective procedure. Recent clinical trials have
      sought to better define the appropriate infectious indications for surgery.
      Despite the improved understanding gained from these studies, the decision to
      operate always must be made on an individual basis with the primary care
      physician, surgeon, patient, and family all involved in the decision-making
      process.

PMID- 12809334
TI  - Nasal deformity in neonates and young children.
AB  - Pediatric nasal deformities comprise a broad range of congenital and acquired
      pathologies. The congenital deformities are rare and often require specific
      surgical interventions. The acquired deformities are more common, and in the
      majority of cases surgical intervention is not necessary. The decision to operate
      is based primarily on the extent of the functional impairment and the severity of
      the aesthetic deformity.

PMID- 12809335
TI  - Oral lesions in young children.
AB  - Oral lesions in very young children usually have a benign presentation, and only
      rarely contribute to significant aerodigestive symptomatology. Management begins
      with early recognition of the pathology and appropriate diagnosis. Hemangiomas,
      lymphangiomas, and teratomas may present with airway compromise or feeding
      difficulties, necessitating early intervention.

PMID- 12809336
TI  - Gastroesophageal reflux and the upper airway.
AB  - EER is a disorder commonly seen in otolaryngologic practice and differs from GERD
      in its clinical manifestations, pathophysiology, and response to treatment. Its
      association with numerous disorders in children should lead otolaryngologists to
      consider this diagnosis in all patients with voice, airway, and swallowing
      complaints.

PMID- 12809337
TI  - Nontuberculous mycobacterial infections of the head and neck.
AB  - Nontuberculous mycobacteria are ubiquitous in the environment. Immunocompetent
      children are commonly infected by these resilient organisms. Cervical
      lymphadenitis, the most frequent head and neck manifestation of NTM infection,
      often presents as chronic, unilateral lymphadenopathy with characteristic
      violaceous overlying skin changes. Diagnosis is ultimately dependent on culture
      or histopathologic examination of specimen obtained through excisional lymph node
      biopsy or FNA. The principal treatment of NTM infection remains the surgical
      excision of diseased tissue. Antibiotics augment surgical therapy and their
      potential role as a single-modality therapy continues to be investigated.

PMID- 12809338
TI  - The lesser of two evils: a contextual view of the English case of the conjoined
      twins.
AB  - In 2000 conjoined twin girls were born in Manchester, England. They were joined
      in such a way that it was impossible to separate them to enable both twins to
      survive. Their bodies were fused at the lower abdomen and they shared an aorta
      and a bladder. Their arms and legs were at right angles to their conjoined trunk.
      The situation of the conjoined twins is of supreme importance as a private
      tragedy for their family. The resulting litigation also presents an important
      landmark in English law. In deciding the fate of the two children, the Court of
      Appeal provided an authoritative review, analysis and application of family law
      and medical law with regard to neonates. The most significant legal legacy of the
      case, however, may well be in the field of criminal law by way of the court's
      interpretation and application of the defences of necessity and self-defence.

PMID- 12809339
TI  - Mining disasters in South Africa: the Rovic Diamond Mine disaster and the
      criminal liability of the mine authorities.
AB  - The South African economy depends heavily on the mining industry. Deep level
      mining--which is a very common occurrence in the South African Mining Industry,
      is fraught with dangers. It is therefore inevitable that these dangers will be a
      constant source of medico-legal involvement. At the end of November 1996, a
      mining disaster occurred at the Rovic Diamond Mine between Boshof and Dealsville.
      At about 1000 metres underground, a mudslide occurred and trapped 20 miners.
      Rescue workers could only retrieve four bodies. Due to the dangers of additional
      mudslides and collapse of the entire slope, the rescue workers were withdrawn.
      The 16 miners were later declared dead by a Court Order after a full
      investigation into the disaster was completed. In this discussion focus will be
      placed on the Rovic Mine Disaster Investigation, the post mortem examination of
      the four victims, the legal declaration of death of the other victims not found
      and the legal accountability of the mine authority.

PMID- 12809340
TI  - Current ethical and other problems in the practice of African traditional
      medicine.
AB  - Medicine in Africa is regarded as possessing its own "life force", not just using
      a system of prescribing. This is because health problems are not only attributed
      to pathological explanations alone, but also to other "forces". Hence,
      traditional healers utter incantations to take care of negative forces which
      militate against achieving cure. Treatment in African traditional medicine (ATM)
      is holistic. It seeks to strike a balance between the patients' body, soul and
      spirit. The problems arise from the infiltration of charlatans into the field,
      the practice of using mystical explanations for ill-health, and inadequate
      knowledge of the properties and clinical use of herbal remedies. Despite its
      problems, ATM can work in parallel with orthodox medicine using its strengths
      rather than its weaknesses. ATM has to be applied within a uniform ethical
      system. Practitioners of ATM must follow the principles of autonomy and
      confidentiality.

PMID- 12809341
TI  - Psychiatric commitment: patients' perspectives.
AB  - OBJECTIVE: The literature pertaining to patients' perceptions of commitment and
      its consequences is limited. The object of this study was to learn more about
      these experiences from the patient's perspective. MATERIAL AND METHODS: 108 court
      committed patients (78% of whom were schizophrenic) were identified for inclusion
      in a retrospective follow-up study. After an interval varying from one to 4.5
      years from time of commitment to follow-up, 76 patients could be contacted, of
      whom 47 were included in the follow-up. RESULTS: The majority of patients felt
      that their court commitment had not been justified and could have been avoided.
      Events and circumstances identified as particularly stressful about commitment
      were confinement in a locked ward, side effects of medication, feelings of
      helplessness, and certain staffbehaviors. Adverse psychological, somatic, and
      social consequences were common. Coercive measures during hospitalization were
      strongly associated with negative feelings about the effect of commitment on
      mental health and about subsequent treatment. The majority, however, also
      remained in treatment after commitment was terminated, said they would return to
      hospital in event of future crisis, and had pertinent comments about how
      commitment could have been avoided. CONCLUSIONS: Many patients who had been court
      committed reported negative feelings about their experiences, but the great
      majority had continued in treatment, both at the termination of commitment and
      later. They also had ideas about how to reduce the negative impact of commitment
      that are worth including in future contingency plans.

PMID- 12809342
TI  - A review of Greek law on human cloning.
AB  - The creation of Dolly, a cloned lamb from adult cells was a major scientific
      breakthrough, which opened new avenues for many research fields such as
      reproductive medicine, transplantation and biotechnology. However this
      achievement brought to public attention the theoretical possibility of human
      reproductive cloning. Inevitably heated debate occurred on several ethical and
      legal consequences of the prospect of human cloning. At the present time there is
      no legal framework in any country to respond to this challenge in a pragmatic way
      in order to protect human rights and at the same time to allow science to work
      for the best interests of mankind. Greece is a European Union country with its
      own traditions, history, culture and beliefs but without political and
      legislative experience in the handling of medical and biotechnological matters.
      This paper aims to discuss the legal issues likely to be raised by the prospect
      of human reproductive cloning in relation to the current state of the Greek legal
      system.

PMID- 12809343
TI  - Consent: a Cartesian ideal? Human neural transplantation in Parkinson's disease.
AB  - The grafting of human embryonic cells in Parkinson's disease is an innovative and
      hopefully useful therapeutic approach. However, it still concerns a very small
      number of patients and is only suggested as a research protocol. We present here
      a study of the problems of information and consent to research within the
      framework of this disease in which the efficacy of medical treatment is
      shortlived. The only French center to use this treatment (Hopital H. Mondor in
      Creteil) has received authorization from the Comite Consultatif National
      d'Ethique (Consultative National Committee on Ethics). Eleven patients were
      treated between 1991 and 1998. The study of the results of a questionnaire sent
      to those patients showed the difficulties met in evaluating the perception of
      information despite intact intellectual capacities in people "prepared to risk
      everything." In France, the duty to inform patients during research procedures is
      regulated by the Huriet Act. However, it is not easy to guarantee genuine consent
      when preliminary information is given to patients psychologically impaired by the
      slow and ineluctable course of their disease. In these borderline cases, a valid
      consent seems to be a myth in terms of pure autonomy when considered with the
      Cartesian aim of elimination of uncertainty. The relevance of this concept of
      genuine consent probably makes more sense as aiming at a Cartesian ideal which is
      perhaps more in the spirit rather than in the letter. It is in that same spirit
      that, from the outset, we propose to define t he practical ways of answering the
      patients' request for information, even sometimes after consent has been given.

PMID- 12809344
TI  - Protection of human participants from risks in biomedical research: an analysis
      of the law of South Africa and international ethical guidelines.
AB  - In order to enhance the quality of lives of South Africans who are afflicted by
      many diseases, medical researchers have been engaged in biomedical research with
      the aim of testing, evaluating newly developed prophylactic and therapeutic
      methods. However, during the testing of newly developed therapeutic methods,
      participants are sometimes exposed to harm which may ruin the remainder of their
      lives or even lead to their deaths. Despite the seriousness of harm which may
      result from research, South Africa does not regard social and economic harms as a
      threat to the welfare and health of participants. Though they utilize the risk
      benefit analysis as outlined by international ethical guidelines to minimize
      harm, this developed criterion has been shown to be an inadequate safeguard for
      the welfare and health of participants as it fails to cover the occurrence of
      scientifically unforeseen risk. To ensure protection of participants, this paper
      suggests the introduction of a precautionary approach in research and also,
      specific reference to South Africa, the recognition of all categories of harm.

PMID- 12809345
TI  - Regulations governing drug trials in Turkey.
AB  - The ethical issues involved in drug trials using human subjects have become a
      challenge to the investigators involved. The needs of the drug industry and the
      increase in the number of such trials have added to these problems. In Turkey
      activity in the field is increasing. The legal provisions governing the conduct
      of drug trials in humans are progressive and improvement is largely directed
      towards better trial design and protection of volunteers.

PMID- 12809346
TI  - A comparison of firearms--related legislation on four continents.
AB  - Firearms are produced in great quantities. Their use is universal, widespread and
      often lethal. The control and supervisory systems of these weapons differ from
      country to country and are an expression of specific attitudes and cultural
      trends of each society on the subjects of individual rights, violence and the
      meaning of firearm possession. This paper presents a comparative study of firearm
      use legislation of four different countries in four different areas of the world
      (Sweden, United States, Japan and Israel). Particular attention will be paid to
      the traditions and cultural characteristics underlying the differences in
      legislative approach.

PMID- 12809347
TI  - Political assassins--the psychiatric perspective and beyond.
AB  - Three cases of highly publicized political assassinations, which occurred during
      the twentieth century, are described. In two of them (Tsafendas and Amir) a head
      of a state was assassinated. In both cases the second author (A.Z.) was involved
      in the psychiatric evaluation of the perpetrator. A third case, in which a head
      of state was badly wounded (Hinckley) is referred due to its overwhelming impact
      on public opinion and legislation. Few similarities are found between the
      perpetrators, who came from different cultures and acted in different eras. The
      psychiatric examination had a crucial role in the outcome of their trial. In
      spite of different milieus the forensic psychiatrist found himself amidst a
      highly charged event. There is no single common denominator characterizing the
      psychopathology of the political assassin. It is suggested that there is a
      spectrum of psychiatric diagnoses ranging from the psychotic perpetrator who
      targets the victim due to his intrapsychic delusional world, to the "sane"
      fanatic who chooses to commit an extreme act of violence in the service of a
      political goal. The criminal act, as well as the trial and the verdict bring in
      its wake a huge emotional public response. Consequently, theories of conspiracy
      as well as legislation initiatives are raised. The forensic psychiatrist should
      adhere to the sphere of his expertise, and it is for the court to decide upon the
      issues of responsibility and fitness to stand trial.

PMID- 12809348
TI  - Revealing the secrets of the body: medical tests as legal evidence in personal
      status disputes in modern Egypt.
AB  - The study seeks to answer the following question: In the field of personal
      status, what kinds of medical tests have been considered reliable and acceptable
      by Egyptian courts of law, what kinds have been less accepted, and why? The main
      finding is that, on the one hand, the judges (qadis) have welcomed tests that
      seek to determine age or to discover physical diseases and/or mental disorders.
      On the other hand, they have been reluctant to introduce tests to determine
      virginity and pregnancy tests, and even more so to introduce paternity tests that
      might bring into light manifestations of moral laxity within Egyptian society and
      jeopardize the future of illegitimate children. In conclusion, the main
      resistance to the reliance on modern medical evidence has not been the lack of
      modern knowledge and technologies or opposition to this, but rather traditional
      moral and social perceptions.

PMID- 12809349
TI  - Informed consent, a legal requirement in the management of patients with
      epilepsy.

PMID- 12809350
TI  - Epilepsy and medical practitioner duty of care in an employment context.
AB  - A medical practitioner who consults with persons with epilepsy has imposed upon
      him or her a duty of care in accordance with current Australian legal authority
      expressed or cited in Rogers v Whitaker, but may also have such a duty imposed in
      a number of circumstances not involving a treating doctor relationship. The
      requirement for sufficient proximity in legal terms exists where the relationship
      is not (or is) a standard doctor-patient relationship, but once duty and
      proximity have been established, it is open to argument, and possibly to future
      judicial determination, that a higher standard of care may exist in relation to
      persons with epilepsy, although the law has yet to recognise differing standards.
      Whilst case law involving claims for damages by workers with epilepsy against
      medical practitioners is sparse, considerable scope appears to exist for the
      novel extension of the duty of care requirements of doctors in employment matters
      involving employees with and without epilepsy.

PMID- 12809351
TI  - Laws and practices relating to euthanasia and assisted suicide in 34 countries of
      the council of Europe and the USA.

PMID- 12809352
TI  - Mini-infarct encephalopathy associated with uncommon microvessel convolute
      formation presenting with presenile dementia.
AB  - A female patient started to suffer from transient ischemic attacks when she was
      47 years of age, followed by increasing predominantly left-side spastic
      tetraparesis, generalized seizures and progressive dementia over a period of 11
      years. She died when she was 58 years of age. On gross examination the brain
      showed enlarged ventricles and arteriosclerotic changes of large extracerebral
      vessels of the circulus arteriosus. Microscopic examination of the atrophic brain
      showed innumerable incomplete microinfarcts in the white and gray matter
      throughout all parts of the brain. In the white matter these lesions were
      characterized by small foci of demyelination and loss of oligodendrocytes while
      occasionally some scavenger cells were seen. Axons seemed to be unaffected or
      displayed irregular axonal regeneratory growth. Any inflammatory reaction failed.
      In the cerebral cortex and subcortical nuclei the lesions showed loss of neurons
      and decrease in synaptophysin expression. Intracerebral arteries showed fibrosis
      or fibrohyalinosis of the entire intracerebral small-vessel network. In addition,
      numerous uncommon clusters of angioma-like telangiectatic vessels were observed.
      Medium-sized ischemic infarcts were found in the right putamen and adjacent
      internal capsule region, left-side dorsolateral brain stem and cerebellar
      hemisphere as well as a left-side pyramidal tract degeneration. Contralateral
      pseudohypertrophy of the inferior olivary nucleus was seen. The clinical and the
      neuropathologic observations made in this patient are compatible with small
      vessel disease characterized by a multicentric special and not yet described type
      of incomplete mini-infarcts in cerebral cortex and white matter accompanied by
      some larger ischemic infarcts of the common type in brain stem and cerebellum.

PMID- 12809353
TI  - Adult-onset subacute sclerosing panencephalitis: clinico-pathological findings in
      2 new cases.
AB  - Subacute sclerosing panencephalitis (SSPE), an uncommon disease usually affecting
      children and adolescents, is caused by persistent measles infection that
      progresses to chronic infection with fatal outcome. The debut of this disease in
      adults is rare, with a small number of cases in the medical literature. This
      article presents the clinical, radiologic and post-mortem neuropathologic
      findings in 2 new cases of women with SSPE (1 of them during pregnancy), which
      showed very atypical clinical characteristics, presentation and evolution. The
      influence of pregnancy on the course of the disease was unfavorable, in keeping
      with earlier reports. Our patients showed a very prolonged biphasal clinical
      course, with a period of disease-free remission that lasted several years.
      Histological study disclosed features of inflammatory disease associated with
      others of a neurodegenerative nature, such as the formation of neurofibrillary
      tangles, which would relate SSPE with other tauopathies.

PMID- 12809354
TI  - Tuberous sclerosis complex with disseminated telencephalic distribution of
      atypical cells and their relation to corticogenesis.
AB  - In 2 cases of tuberous sclerosis complex (TSC), a disseminated distribution of
      atypical cells throughout the white matter and cortex of the telencephalon has
      been found. No cortical tubera were observed. In 1 of the cases, ventricular wall
      tumors (giant astrocytomas) were present. Stripes and candle guttering
      excrescences of groups of atypical cells perpendicular to the ventricular wall
      and to the cortical surface indicate erroneous genetic information in sets of
      neuroepithelial germ cells. This is compatible with the somatic second hit
      hypothesis effective in addition to the basic defect of TSC1 and TSC2 genes. The
      normal age-correspondend corticogenesis with regular layering and regular
      differentiation of neurons and glia without any cortical malformation or
      dysplasia and the sparing of allocortical parts of the telencephalon
      (hippocampus) as well as of basal ganglia, cerebellum, brain stem and spinal cord
      point to the rather late appearance of atypical cells which manifest in loco and
      do not interfere with corticogenesis. The bidirectional potential of atypical
      cells is obvious by their strong GFAP and APP surface staining. This coexpression
      indicates glial as well as neuronal features and emphasizes the relatively low
      level of differentiation of these cells. In their disseminated localization in
      our cases, these cells do not form tumors in the telencephalic white matter or
      cortex thus escaping sonographic detection before birth.

PMID- 12809355
TI  - Quantitative investigation of nuclear morphology in glioblastomas and its
      relation to survival time.
AB  - OBJECTIVE: To investigate the influence of nuclear morphology of tumor cells on
      survival time of patients with primary glioblastomas. STUDY DESIGN: Tumor cell
      nuclei have been measured in paraffin sections from 51 glioblastomas (Ki-67
      immunostaining). In each tumor, the region with the highest proliferative
      activity has been selected for performing the morphometric analysis. Nuclear
      area, shape variables (roundness factor, Fourier amplitudes) and the
      proliferation index Ki-67 have been determined. Statistical relationships between
      these variables have been tested by principal component analysis and Spearman's
      correlation analysis. The survival time has been tested using Kaplan-Meier
      analysis. The influence of morphometric variables on survival time and on the
      time until recurrence has been tested by Cox analysis. RESULTS: There is a
      significant correlation of mean value and standard deviation of nuclear area with
      shape variables. Cox analysis showed a significant influence of the quantitative
      morphologic variables on survival time for patients with and without complete
      surgical resection. For patients with complete surgical resection, there was a
      distinct influence of mean nuclear area on survival time. Patients with
      incomplete surgical resection of the tumors had a significantly shorter survival.
      No significant influence of the variables on the time from surgery to recurrence
      could be shown. CONCLUSION: Quantitative morphology of tumor cell nuclei in our
      set of glioblastoma cases showed a statistically significant relation with the
      survival time of the patients, indicating the biological significance of nuclear
      morphology in glioblastomas.

PMID- 12809356
TI  - Atypical paraneoplastic syndrome associated with anti-Yo antibodies.
AB  - OBJECTIVE: Polyneuropathy, myopathy and spasticity have not been described as a
      manifestation of a neurologic paraneoplastic syndrome (NPS) associated with anti
      Yo antibodies (anti-Yo). CASE HISTORY: The patient is a 60-year-old woman with a
      history of ovarectomy, salpingectomy, hysterectomy and omentectomy because of
      ovarian cancer with peritoneal carcinosis. From May to September 1999, she
      received chemotherapy with carboplatin and docetaxel. In June 1999, weaknesses of
      the lower limbs began to appear. Neurologic investigation revealed bilateral
      ptosis with right-sided predominance, exaggerated deep tendon reflexes, discrete
      distal weakness, wasting of the upper limbs and diffuse weakness of the lower
      limbs. She had slight CK elevation, elevated lactate dehydrogenase and aldolase
      levels. Testing for anti-neuronal antibodies revealed high serum titers of
      antibodies against the cytoplasm of Purkinje cells, confirmed as anti-Yo by
      immunoblot with recombinant proteins. CSF investigations showed 12/3 cells and
      positive oligoclonal bands. MRI of the brain showed bilateral, old ischemic basal
      ganglia lesions exclusively. Visually evoked potentials gave prolonged P100
      latencies bilaterally. Nerve conduction studies and electromyography revealed
      motor polyneuropathy of the lower limbs. Muscle biopsy from the right anterior
      tibial muscle showed non-specific myopathic features. CONCLUSION: Polyneuropathy,
      myopathy and tetraspasticity may be the exclusive manifestations of an atypical
      NPS associated with anti-Yo. Anti-Yo may persist for years without relapse of the
      primary tumor.

PMID- 12809357
TI  - Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard
      -a standardized fixed combination of Andrographis paniculata Nees, with
      Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza
      glabra L. extracts in patients with Familial Mediterranean Fever.
AB  - Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a
      standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus
      senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special
      extracts standardized for the content of Andrographolide (4 mg/tablet),
      Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel
      groups of patients. The study was conducted in 24 (3-15 years of both genders)
      patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of
      series A (verum) and 10 patients received series B product (placebo). The study
      medication was taken three times of four tablets daily for 1 month. Daily dose of
      the andrographolide--48 mg. The primary outcome measures in physician's
      evaluation were related to duration, frequency and severity of attacks in FMF
      patients (attacks characteristics score). The patient's self-evaluation was based
      mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia,
      erysipelas-like erythema. All of 3 features (duration, frequency, severity of
      attacks) showed significant improvement in the verum group as compared with the
      placebo. In both clinical and self evaluation the severity of attacks was found
      to show the most significant improvement in the verum group. Both the clinical
      and laboratory results of the present phase II (pilot) clinical study suggest
      that ImmunoGuard is a safe and efficacious herbal drug for the management of
      patients with FMF.

PMID- 12809358
TI  - Neuroprotective effects of tanshinones in transient focal cerebral ischemia in
      mice.
AB  - Tanshinones are the major lipid soluble pharmacological constituents of Danshen,
      the dried roots of Salvia miltiorrhiza Bunge (Labiatae), a well known traditional
      Chinese medicine used for the treatment of cerebrovascular diseases including
      stroke. Potential neuroprotective effects of tanshinones IIA (TsIIA) and IIB
      (TsIIB) were examined in adult mice subjected to transient focal cerebral
      ischemia caused by middle cerebral artery occlusion (MCAo). Our results revealed
      that TsIIA (16 mg/kg) readily penetrated the blood brain barrier reaching a peak
      concentration of 0.41 nmol/g brain wet weight 60 minutes after intraperitoneal
      injection and decreased slowly over several hours. Twenty-four hours after middle
      cerebral artery occlusion, brain infarct volume was reduced by 30% and 37%
      following treatment with TsIIA and TsIIB, respectively. The reduction in brain
      infarct volume was accompanied by a significant decrease in the observed
      neurological deficit. Tanshinones or other structurally related compounds may
      have potential for further development as neuroprotective drugs.

PMID- 12809359
TI  - Inhibition of DNA synthesis by carvacrol in mouse myoblast cells bearing a human
      N-RAS oncogene.
AB  - Monoterpenes are dietary components found in the essential oils of a wide variety
      of plants. A number of these monoterpenes have antitumor activity. We have
      investigated the effects of carvacrol obtained by fractional distillation of
      Origanum onites L. essential oil, on DNA synthesis of N-ras transformed myoblast
      cells, CO25. Incubation of the cells with different doses of carvacrol prevented
      DNA synthesis in the growth medium and ras-activating medium, which contains
      dexamethasone. This result demonstrates that carvacrol inhibits growth of
      myoblast cells even after activation of mutated N-ras oncogene, suggesting the
      possibility that carvacrol may find application in cancer therapy.

PMID- 12809360
TI  - In vitro antiproliferative effects on human tumor cell lines of extracts from the
      Bangladeshi medicinal plant Aegle marmelos Correa.
AB  - In the present paper we show that extracts from Aegle marmelos Correa are able to
      inhibit the in vitro proliferation of human tumor cell lines, including the
      leukemic K562, T-lymphoid Jurkat, B-lymphoid Raji, erythroleukemic HEL, melanoma
      Colo38, and breast cancer MCF7 and MDA-MB-231 cell lines. Molecules present
      within the studied Aegle marmelos C. extracts were identified by gas
      chromatography/mass-spectrometry analysis; three derivatives (butyl p-tolyl
      sulfide, 6-methyl-4-chromanone and butylated hydroxyanisole) were found to
      exhibit strong activity in inhibiting in vitro cell growth of human K562 cells.
      The antiproliferative activity of these compounds was found to be comparable to
      that of known antitumor agents, including cisplatin, chromomycin, cytosine
      arabinoside and 5-fluorouracil. In addition, the antiproliferative activity of
      butyl-p-tolyl sulfide, 6-methyl-4-chromanone and 5-methoxypsolaren was associated
      to activation of the differentiation pattern of K562 cells.

PMID- 12809361
TI  - Isolation and synthesis of TNF-alpha release inhibitors from Fijian kawa (Piper
      methysticum).
AB  - Two unique evidence that cancer incidence rates in Fiji were unusually low,
      compared with those of another Pacific islands and that green tea beverage is an
      acknowledged cancer preventive in Japan, allowed us to study a local beverage in
      Fiji, kawa (kava kava) or yangona (Piper methysticum) belonging to Piperaceae. We
      isolated five known kawapyrones (kavapyrones) (1-5) and a new additional
      kawapyrone, 7,8-epoxyyangonin (6), from kawa MeOH extract and subjected them to
      TNF-alpha (tumor necrosis factor-alpha) release assay from BALB/3T3 cells treated
      with okadaic acid, a tumor promoter. 5,6-Dehydrokawain (desmethoxyyangonin)(1)
      and yangonin (4) significantly inhibited TNF-alpha release with IC50 values of 17
      microM and 40 microM; a potency as great as (-)-epigallocatechin gallate (EGCG)
      isolated from green tea extract. Among the experiments with 1-5, dihydrokawain
      (2) was unique in showing the strongest inhibitory activity against TNF-alpha
      release in mice, but the weakest activity in the cells. We synthesized 5,6
      dehydrokawain (1) and yangonin (4) via three steps from the dianion of ethyl
      acetoacetate achieving a good yield and determined their conformations by high
      resolution NMR and x-ray crystallographic analysis.

PMID- 12809362
TI  - Immunologically active O6-branched (1-->3)-beta-glucan from the lichen Thamnolia
      vermicularis var. subuliformis.
AB  - A lentinan-type gel-forming beta-glucan, Ths-2, has been isolated in about 1.5%
      yield from the alkali extract of the lichen Thamnolia vermicularis var.
      subuliformis, using ethanol fractionation, dialysis and gel filtration. The mean
      Mr of Ths-2 was determined by GP-HPLC to be 67 kD, and the optical rotation was
      measured to be -14 degrees. The structure of Ths-2 was further elucidated by
      methylation analysis by GC-MS, 1H- and 13C-NMR spectroscopy and selective
      enzymatic hydrolysis with exo-(1 --> 3)-beta-D-glucanase followed by analysis of
      oligosaccharides by HPAEC-PAD. Ths-2 was found to be consisting of a (1 --> 3)
      beta-D-glucopyranosyl main chain with branches of a (1 --> 6) linked
      glucopyranosyl unit on every third unit of the main chain. Similar polysaccharide
      structures have been described from fungi, but this is the first report of a
      lentinan-type (1 --> 3)-beta-D-glucan from a lichen species. The immunomodulating
      activity of Ths-2 was tested in an in vitro anti-complementary assay, and proved
      to be strongly active.

PMID- 12809363
TI  - Bioactive crude plant seed extracts from the NCAUR oilseed repository.
AB  - Over four-hundred crude extracts from 202 plant species distributed among 131
      plant families were evaluated for their bioactivity against brine shrimp (Artemia
      salina). Activity was determined for both the organic (CH2Cl2:MeOH) and aqueous
      extracts against A. salina in a 96 well-plate assay. Of the greater than four
      hundred extracts tested, 21 organic and 6 aqueous extracts demonstrated potent
      cytotoxic activity (LC50 = < 100 microg/ml). Three of these organic extracts
      (Crateva religiosa, Diospyros dichrophylla, and Olax subscorpioidea) were chosen
      for chemical investigations due to their high activity and a lack of prior
      investigations. Chemical analysis of these extracts resulted in the isolation of
      oleanolic acid (1) and 4-epi-hederagenin (2) from C. religiosa, isodiospyrin (3)
      from D. dichrophylla, and santalbic acid (4) from O. subscorpioidea.

PMID- 12809364
TI  - In vitro inhibition of human cytochrome P450-mediated metabolism of marker
      substrates by natural products.
AB  - Spices, herbal and black teas, and soybean products were analyzed for their
      capacity to inhibit in vitro metabolism of drug marker substrates by human
      cytochrome P-450 (CYP) isoforms. Inhibition of drug metabolism was determined
      using aliquots or infusions from these products in a fluorescence-detection
      assay. Aliquots and infusions of all natural product categories inhibited 3A4
      metabolism to some extent. Of the 26 aliquots from teas and spices further tested
      with 2C9, 2C19 and 2D6, many demonstrated significant inhibitory activity on the
      metabolism mediated by these isoforms. Black teas and herbal tea mixtures were
      generally more inhibitory than single-entity herbal teas. Spices and single
      entity herbal teas showed species-specific isoform inhibition with sage, thyme,
      cloves, St John's Wort and goldenseal having the highest activity against several
      isoforms. Seven soybean varieties tested, as well as daidzein and genistein
      isolated from soybean, were found to inhibit 3A4-mediated metabolism. Genistein
      was found to inhibit 3A7- but not 3A5-mediated metabolism of the marker
      substrate. Assessment of the in vitro CYP inhibition potential for these natural
      products has important implications for predicting the likelihood of natural
      product-drug interactions if these products are taken concomitantly.

PMID- 12809365
TI  - Effect of three vegetal sources of propolis on macrophages activation.

PMID- 12809366
TI  - Bioactivity of secoiridoid glycosides from Centaurium erythraea.
AB  - As part of our on-going search for bioactive compounds from Scottish plants, two
      secoiridoid glycosides, swertiamarin and sweroside, have been isolated from the
      aerial parts of Centaurium erythraea Rafn (Family: Gentianaceae) by reversed
      phase preparative HPLC coupled with a photo-diode-array detector. The structures
      of these compounds were elucidated unambiguously by UV, FABMS and extensive 1D
      and 2D NMR spectroscopic analyses and also by comparing experimental data with
      literature data. Antibacterial, free radical scavenging activities and general
      toxicity of these glycosides have been assessed. Both compounds inhibited the
      growth of Bacillus cereus, Bacillus subtilis, Citrobacter freundii and
      Escherichia coli. While swertiamarin was also active against Proteus mirabilis
      and Serratia marcescens, sweroside inhibited the growth of Staphylococcus
      epidermidis. Swertiamarin and sweroside exhibited significant general toxicity in
      brine shrimp lethality bioassay and the LD50 values were 8.0 microg/ml and 34
      microg/ml, respectively, whereas that of the positive control podophyllotoxin, a
      well known cytotoxic lignan, was 2.79 microg/ml. Chemotaxonomic implications of
      these compounds in the family Gentianaceae have also been discussed briefly.

PMID- 12809367
TI  - Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications.
AB  - Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used
      to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate
      that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia
      (mastalgia) is beneficially influenced by an AC extract. In addition, numerous
      less rigidly controlled studies indicate that AC extracts have also beneficial
      effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia
      is most likely due to a latent hyperprolactinemia, i.e. patients release more
      than physiologic amounts of prolactin in response to stressful situations and
      during deep sleep phases which appear to stimulate the mammary gland.
      Premenstrually this unphysiological prolactin release is so high that the serum
      prolactin levels often approach heights which are misinterpreted as
      prolactinomas. Since AC extracts were shown to have beneficial effects on
      premenstrual mastodynia serum prolactin levels in such patients were also studied
      in one double-blind, placebo-controlled clinical study. Serum prolactin levels
      were indeed reduced in the patients treated with the extract. The search for the
      prolactin-suppressive principle(s) yielded a number of compounds with
      dopaminergic properties: they bound to recombinant DA2-receptor protein and
      suppressed prolactin release from cultivated lactotrophs as well as in animal
      experiments. The search for the chemical identity of the dopaminergic compounds
      resulted in isolation of a number of diterpenes of which some clerodadienols were
      most important for the prolactin-suppressive effects. They were almost identical
      in their prolactin-suppressive properties than dopamine itself. Hence, it is
      concluded that dopaminergic compounds present in Vitex agnus castus are
      clinically the important compounds which improve premenstrual mastodynia and
      possibly also other symptoms of the premenstrual syndrome.

PMID- 12809368
TI  - Scientific reporting of unscientific data--a case of Ginkgo biloba being
      miscredited.

PMID- 12809369
TI  - Ground one.
AB  - The events of September 11th, 2001, have had long-lasting effects on our culture,
      interpersonal relationships, understanding of evil intent and terrorism, and
      approach to and treatment of trauma states. This article is a personal account of
      September 11th by a junior attending psychiatrist as he experienced it from St.
      Vincent's Hospital, the closest level-one trauma center and coordinated medical
      response center to the World Trade Center.

PMID- 12809370
TI  - The role of the primary clinician in the multidisciplinary team.
AB  - This article explores the role of the primary clinician as an integral member of
      the modern inpatient psychiatric treatment team, as it is practiced on the
      Professionals in Crisis program at The Menninger Clinic. The modern inpatient
      team consists of individuals from multiple disciplines and acts as an embodiment
      of the neo-biopsychosocial model, with each team member providing not only a
      unique perspective on viewing the patient but also offering unique opportunities
      to aid in creating an environment that is conducive to change. The role of the
      primary clinician as the conduit of communication between various treaters and as
      the individual who provides oversight of the patient's treatment is described.
      The unique therapeutic elements that this role brings to treatment, with
      particular respect to the four cornerstones of psychotherapeutic success
      (alliance, activity, focus, and expectation) are defined.

PMID- 12809371
TI  - Clinical applications of recent research on electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) has been in use since the late 1930s to treat a
      variety of severe mental illnesses, most notably major depression. Current
      research efforts focus on patient selection, memory impairment, and high
      posttreatment relapse rates. Psychopathological factors such as psychosis and
      severe psychomotor retardation predict favorable response to ECT in depression.
      Technical variables that affect memory include electrode placement, stimulus
      intensity, and treatment frequency. Strategies to reduce posttreatment relapse
      rates include maintenance ECT and aggressive medication combinations. In this
      article, I review recent research that bears on these aspects of ECT practice.
      Additionally, I review some findings on the neurobiological effects of ECT.

PMID- 12809372
TI  - Working with pathological and healthy forms of splitting: a case study.
AB  - The author illustrates through a case discussion how he understands the concept
      of splitting and how he makes use of that understanding in tracking, and at
      times, interpreting movement of the unconscious transference and
      countertransference. He views splitting not simply as a primitive defense but
      also as essential to early emotional development and to healthy psychological
      maturation in the course of analytic work. In the analytic relationship discussed
      in this article, the author presents both aspects of splitting--as a primitive
      defense and as a healthy movement toward new and more complex object relatedness.
      Difficulties arise when one fails to distinguish pathological from healthy but
      immature forms of splitting. Healthy splitting in its beginnings represents an
      important developmental step that serves as a transition to ambivalence and
      mature integration. The author demonstrates the importance of the analyst's
      capacity to distinguish pathological splitting from healthy splitting during
      periods of analytic impasse.

PMID- 12809373
TI  - Fragmented attachments: the paranoid-schizoid experience of loss and persecution.
AB  - The author discusses paranoid-schizoid patients who have yet to deal with whole
      object depressive fears of harming one's object. Their paranoid-schizoid anxiety
      is more a combination of dread, paranoia, and fear of destroying one's object
      with neediness, envy, and other oral desires. In this part-self and part-object
      world, destruction is absolute. Ego functions and object relational capacities
      such as guilt and grief are not yet fully consolidated. The part-object is not
      only destroyed but is also equally capable of magically resurrecting itself to
      seek revenge. Fear of annihilation of the self and object, as well as desperate
      attempts at keeping each other alive, are the primary focus of this early anxiety
      state. These infantile fears are at the root of certain difficult treatment
      situations. Within the transition from paranoid-schizoid to depressive, the ego
      struggles with highly exaggerated and distorted fantasies of persecution, loss,
      and primitive guilt by resorting to crude and often self-destructive mechanisms.
      These include splitting, projective identification, and idealization. During the
      course of analytic treatment, three overlapping phases are distinguishable.
      Acting out is the main theme of early treatment. As this externalization of
      internal conflict is analyzed and contained, a second phase of intrapsychic
      struggle emerges. The patient exhibits a paralyzing battle between certain ego
      object ties and the striving of a defensive death instinct. If the analytic
      relationship is able to withstand passage through these difficult phases, the
      patient begins to work through more core issues of persecutory loss and
      annihilation. Case material is used for illustration.

PMID- 12809374
TI  - A study to assess patient satisfaction of transitioning from Medicaid to managed
      care by sickle cell patients in Hampton Roads, Virginia.
AB  - Transition issues faced by the sickle cell patient who has a significant chronic
      illness or disability are many and often life threatening. The problems that are
      faced in transitioning from Medicaid to managed care are many that could hinder
      the process and patient satisfaction. Such problems during the transition periods
      could stem from interrupted health care services; improperly coordinated
      services; inappropriate intervention; and inappropriate or unfounded
      psychologically diagnosed cases (Blum, 1993). It is not known which health care
      programs are cost-effective and which are not. Nor is it known which health care
      program best meets the needs of patients with chronic illnesses or varying levels
      of severity; and it is not known if health status actually improves as a result
      of transitioning from one program to another. What factors then impact the
      satisfaction levels in transitioning from Medicaid to managed care for sickle
      cell patients in Hampton Roads, Virginia? This study looked at patient
      satisfaction with the transition from Medicaid to managed care as related to the
      cost of care, quality of care, and access to care.

PMID- 12809375
TI  - Help-seeking and risk-taking behavior among Black street youth: implications for
      HIV/AIDS prevention and social policy.
AB  - This article explores and analyzes the help-seeking and risk-taking behavior of
      Black urban street youth in Washington, DC, USA and Cape Town, South Africa. The
      target population of 100 youths came from the streets of Washington, DC and Cape
      Town, South Africa. Structured face-to-face interviews and direct observation of
      informal and formal settings where youths congregated were used to gather data.
      Major findings indicate that the majority received high levels of support from
      families and friends. In terms of formal systems, social and mental health
      services are viewed as much less accessible or useful. Youths were knowledgeable
      about HIV/AIDS but did not translate this into safer sexual practices.
      Implications for health and social policy are outlined.

PMID- 12809376
TI  - Arthritis and the role of the physician in nonmalignant pain and disability.
AB  - Most adults will experience at least one episode of low back pain. It is the
      second most common symptom that prompts visits to the doctor's office. Back pain
      is subjective and often presents with few objective findings on a physical exam.
      It remains a diagnostic and therapeutic challenge to many practitioners.
      Psychosocial and economic issues, such as litigation, workers' compensation
      claims and depression may have an impact on the management and treatment outcomes
      (Helfgott, MD, Simon M., 2001). Workers' compensation programs have a mandate to
      compensate only those who deserve compensation. Therefore, disability rating
      exists to sort out those who cannot work from those who will not work (Sullivan,
      MD, 1992). When treating chronic nonmalignant pain the physician should make a
      decision to either function as the patient's advocate or the rater of the
      patient's limitations. This will increase the likelihood of a healthy patient
      physician relationship during what may be a very vulnerable and stressful period.
      It is very important to obtain sound acceptable documentation of the diseased
      patient's limitations by choosing the proper cost effective diagnostic studies,
      which are appropriate for each individual case. This will result in establishing
      an accurate and correct diagnosis. This process should lead to offering the
      patient treatment options designed to achieve pain reduction and improvement of
      his/her activity of daily living.

PMID- 12809377
TI  - The context of religiosity, social support and health locus of control:
      implications for the health-related quality of life of African-American
      hemodialysis patients.
AB  - Most African-Americans choose hemodialysis as a treatment regimen when diagnosed
      with renal failure modality. Some researchers suggest that African-American
      hemodialysis patients' health-related quality of life enables them to cope with
      and survive this type of difficult renal therapy better than other racial and
      ethnic groups. This article examines how the sociocultural and social
      psychological constructs of religiosity, social support and health locus of
      control, relate to the health-related quality of life for this population group.

PMID- 12809378
TI  - Motivated but fearful: welfare reform, disability, and race.
AB  - The Personal Responsibility and Work Opportunity Reconciliation Act (1996)
      instituted reforms in welfare that focused on mandatory work requirements. It
      imposes strict requirements and lifetime limits that force non-exempt individuals
      to work or risk sanctions. The law particularly impacts persons with disabilities
      because of the substantial numbers who believe they are unable to work. This
      article uses findings from a research study to discuss barriers faced by
      individuals with physical disabilities who are forced to find work under welfare
      reform. It highlights the experiences of African Americans who have the added
      burden of health disparities because of discriminatory and differential practices
      in diagnoses, treatment, access, and utilization. It also presents practice
      implications.

PMID- 12809379
TI  - Predicting weekly earning for consumers with severe disabilities: implications
      for welfare reform and vocational rehabilitation.
AB  - This 1999 research analyzed selected descriptive variables for consumers with
      significant disabilities, who were successfully employed. The goal was to
      investigate employment outcomes for consumers whose cases were closed as
      successfully employed. Human capital theory provided the theoretical
      underpinnings for evaluating the findings. This study empirically assessed
      factors which contributed to increased weekly earnings for consumers of state
      vocational rehabilitation services with severe disabilities. The variables
      included in this study were weekly earnings at closure, correlated with year last
      employed, highest grade completed, and birth year. The study found that 17.2% of
      variability in weekly earnings of the significantly disabled consumers can be
      predicted by these variables. Education, age, and work experience were found to
      be predictors of potential earning power. These findings can be used to provide
      the foundation for the development of reliable program evaluation as well as
      clinical interventions. This study links outcomes to the services provided. It
      further provides the data necessary to support policy development in the areas of
      rehabilitation and welfare reform.

PMID- 12809380
TI  - Foster care children with disabilities.
AB  - Each year the number of children who enter the foster care system grows because
      the number of children who are vulnerable to abuse, neglect and/or poverty grows.
      Children with disabilities are a particularly vulnerable subset of this already
      vulnerable population. What are the implications of conceptual and methodological
      issues in theories of disability for estimates of children with disabilities in
      foster care? To what extent do children in the foster care system have
      disabilities? What are implications of existing health care coverage strategies
      (Medicaid, managed care, etc.) for the health and well-being of foster care
      children with disabilities? Conceptual and operational definitions of disability
      are reviewed. Descriptive statistics based on a secondary analysis of 1998
      administrative AFCARS data are used to summarize the extent of disabilities. In
      addition, existing empirical studies and public policies on national and state
      health care insurance strategies are analyzed.

PMID- 12809381
TI  - Public housing accommodations for individuals with disabilities.
AB  - The federal Housing Act of 1962 as amended and the subsequent laws of
      accommodations insure that all groups within American society, including those
      with disabilities, have access to housing opportunities. In spite of the clear
      provisions of various laws of accommodations enacted after 1962, it is
      questionable whether disabled individuals are adequately served by resident
      programs operated by Public Housing Agencies (PHAs) because rates of poverty,
      unemployment, domestic violence, and suicide are much higher among people with
      disabilities than in the nondisabled population. There are approximately 5
      million residents living in 2.5 public housing units nationwide. New York, Puerto
      Rico, Chicago, Philadelphia and Baltimore have the five largest PHAs in the
      country. In combination, they rent 320,000 of the 1,300,495 inventory of rental
      properties owned by the country's 3,400 PHAs. Elderly and disabled residents
      without children account for 43% of all public housing families in the country.

PMID- 12809382
TI  - Addressing students' social and emotional needs: the role of mental health teams
      in schools.
AB  - Children in today's society face many stresses from a variety of sources that
      have a major impact on thier psychosocial adjustment and academic performance in
      school. These stressful events and thier consequences on the quality of life and
      academic success are particularly significant among low-income and ethnic
      minority students in American society. Many schools have adopted strategies to
      help students who are impacted by stressful life events to deal affectively with
      their problems in an attempt to reduce school failure and school dropout rates
      among these students. Most notable among these strategies are school-based mental
      health programs including the establishment of school-based mental health teams
      which seek to proactively address individual student concerns while improving the
      general climate of schools. The evidence seems to support the claim that these
      school-based services have a positive impact on students' social and emotional
      well-being as well as on their academic achievements. However, with more careful
      monitoring and much more consistent support from administrators and policy
      makers, these school-based approaches can more fully realize their potential to
      enhance the quality of life and to positively impact the future of many poor and
      ethnic minority students.

PMID- 12809383
TI  - Parent-adolescent interaction: influence on the academic achievement of African
      American adolescent males.
AB  - As the achievement gap between African American and while students persists, an
      examination of factors outside the school setting are essential. Acknowledging
      the dynamics of family environment as perceived by African American adolescent
      males is apposite to understanding the relationship between family environment
      and academic achievement. Utilizing an ecological perspective, this study
      describes the characteristics of family process variables and analyzes the
      adolescents' perception of parent-adolescent interaction and its influence on
      their psychological well-being. Results indicate that a substantial proportion of
      the 179 adolescent males who perceived parent-adolescent interaction as positive
      and were identified as having a stable psychological well-being, were more likely
      to have average to above-average grade point averages, high Stanford Nine scores
      and high achievement group membership, than those adolescent males who did not
      perceive parent-adolescent interaction as positive.

PMID- 12809384
TI  - The state of mental health services for children and adolescents: an examination
      of programs, practices and policies.
AB  - This article presents an overview of the state of mental health services for
      children and adolescents. It provides a brief historical review of policies
      affecting mental health services for children and adolescents with emotional and
      behavioral disorders. It discusses the roles of various systems in the provision
      services for emotionally and behaviorally disordered children and adolescents,
      and the need for cross-systems collaboration and funding. A model psycho
      educational day treatment program. City Lights, is highlighted as an approach to
      serving inner-city African American adolescents with a profile of services and of
      the types of youth best served by such a program.

PMID- 12809385
TI  - 100% access, zero health disparities, and GIS: an improved methodology for
      designating health professions shortage areas.
AB  - The (Health Professions Shortage Areas) HPSA designation process was developed as
      a mechanism to identify primary care shortage areas eligible for participation in
      specific federally funded programs including a 10% Medicare supplement, the
      National Health Service Corps, and health professions training programs. The
      purpose of this paper was to explore the utility of Geographic Information
      Systems (GIS) technology as an improved methodology for obtaining HPSA
      designation status for geographic areas. Results showed that GIS identified 24
      Medical Services Study Areas (rational planning areas) in Los Angeles County that
      met the minimum 3500:1 population-to-primary-care physician ratio for geographic
      area HPSA designation compared to only three that currently are identified.
      Authors concluded that restructuring of the state/county responsibilities for
      HPSA designation is long overdue and that use of GIS as a required methodology
      would help ensure that all areas in any state that meet the intent of federal
      legislation are included.

PMID- 12809386
TI  - A study of the influence of protective factors as a resource to African American
      males in traditional batterers' interventions.
AB  - The purpose of this study was to examine the relationship between protective
      factors and the responses of African American males in traditional batterers'
      interventions. African American male batterers have been viewed as responding
      poorly to batterers' interventions and were reported in the literature as at risk
      for dropout and treatment failure. This research proposed that there were
      culturally related protective factors that enhanced traditional interventions for
      African American males, increasing their potential for changing abusive
      behaviors. This within-group study used secondary data to examine the influence
      of protective factors on the responses of 268 active duty Navy African American
      males. They were a sub-sample of 861 males randomly assigned to one of four
      different interventions for batterers. The interventions included a cognitive
      behavioral men's group, couple's group, safety and stabilization group, and a
      control group. Each of their cases had been officially substantiated by the Navy
      for assault of their spouses. The measures for the protective factors of
      religion, self-esteem, and family support were drawn from the original study's
      self-report measurement tool. The results of the statistical analyses were found
      to be significant. The protective factors performed as social controls for
      reducing certain types of abusive behaviors. Little research has been conducted
      on the influence of cultural factors on batterers intervention outcome for
      African Americans. This study established a strong support for further research.

PMID- 12809387
TI  - African centered family healing: an alternative paradigm.
AB  - African centered family healing posits an alternative paradigm that can be used
      as a model for family healing. Effective intervention begins with the recognition
      that what we have been doing has not been working for African American families
      (Boyd-Franklin, 1989; Kambon, 1998; Logan, Freeman and McRoy, 1990; Owusu-Bempah,
      1999; and Weaver, 1992). Social work intervention efforts must integrate mental
      health constructs that exist in the communities we are attempting to serve. One
      such concept is communal knowledge. Another such concept is communal values. When
      one joins communal knowledge and values, one begins to restructure the
      understanding of mental health in the African American family. The family unit
      must be viewed as interdependent. This understanding is requisite to family
      healing. It is therefore necessary that we change our thinking and then our
      actions. This article posits that social workers must become social healers.

PMID- 12809388
TI  - A model program for African American children in the foster care system.
AB  - The children who come into shelter care are usually children who have been abused
      and neglected. Many have experienced numerous placements. Typically, these
      children have had to perform adult roles, such as caring for their own siblings
      or parents. They have not had the opportunity to negotiate the developmental
      phases of childhood in a healthy manner. Few appropriate socialization behaviors
      have been modeled. Many of these children demonstrate a sense of mistrust,
      hopelessness and serious academic problems. These are factors that have the
      potential to lead to life disabilities. Based on their work in the foster care
      system, the authors maintain that interventions at any level in the continuum of
      care can contribute to the healthy development of children. Effective
      interventions at the shelter care level may significantly reduce the foster
      child's potential for lifelong disabilities. This article will focus on African
      American males in shelter care between the ages of 7 and 14. At this juncture in
      their lives, these children are especially open to therapeutic interventions. The
      authors believe the presented model has application to all racial and ethnic
      groups, and aspects of the model are applicable to other settings in the foster
      care system.

PMID- 12809389
TI  - Missed opportunities and unlimited possibilities: teaching disability content in
      schools of social work.
AB  - The issue of disability is paramount to the delivery of social services to a
      vulnerable population--a noble cause of the social work profession. Yet social
      workers are not the purveyors of services to the disabled. As a way of
      determining the impact of social work in the field of disability, an analyses of
      courses are made of disability and school social work content. While this
      comparison of courses may seem perilous it is important to note that a
      significant portion of the disabled community are serviced in the schools. The
      purpose of this article is to raise the professional consciousness of social
      workers to their responsibility to the treatment and policy development for those
      who have disabilities. It challenges schools of social work to re-think their
      course offerings or to reorganize course content to include more information on
      disabilities.

PMID- 12809390
TI  - Long-term results of cardiac transplantation.
AB  - Heart transplantation is a successful therapeutic option for patients with end
      stage heart cardiomyopathy. From April 1991 to December 2000, 345 patients
      underwent heart transplantation at the Juan Canalejo Hospital. The mean age of
      recipients was 54.5 +/- 11.4 years; 286 (83%) were male patients. Idiopathic
      (52.2%) and ischemic (34.9%) end-stage cardiomyopathy were the main causes
      leading to transplantation. Ninety-four patients had undergone a previous heart
      operation. The mean left ventricular ejection fraction was 22.8 +/- 11.4. Forty
      patients (11.5%) were transplanted in urgent (status I) condition. The mean time
      spent on the waiting list was 35.9 days. In-hospital mortality was 10.6% and 24%
      for transplantations performed on an elective and urgent basis, respectively.
      Operative (30-day), one-year and six-year survival was 87.2%, 81.3% and 64%,
      respectively. In terms of actuarial survival, there were no significant
      differences with regard to the recipient's age, sex, previous cardiac surgery,
      and the etiology of the end-stage cardiomyopathy. The six-year actuarial survival
      for recipients receiving hearts from female donors was 59% compared with 72% for
      male donors (p = 0.05). There has been a low incidence of rejection, as well as
      cardiac graft vasculopathy. Actuarial survival at six years was 66% for patients
      transplantated on an elective basis compared with 57% for patients transplanted
      on an urgent basis (p = 0.04). The aim of the study was to evaluate long-term
      results for patients who underwent orthotopic heart transplantation. In our
      experience, status I is associated with a higher mortality.

PMID- 12809391
TI  - Early and late results of partial left ventriculectomy: single center experience
      and review of the literature.
AB  - AIM: To evaluate early and late outcome of partial left ventriculectomy (PLV) in
      a single center and to conduct a review of the literature. METHODS: From February
      1996 to August 2001, 24 patients with dilated cardiomyopathy (DCM) (12
      idiopathic, 12 ischemic) underwent PLV. Perioperative and follow-up data were
      prospectively entered into a database and analyzed. An observational analysis of
      the literature was carried out of all the published series of PLV reporting on >
      or =15 patients. RESULTS: In our series there were 22 males with amean age of 65
      years (range 49 to73). Of the 22, there were 3 (12.5%) in-hospital deaths. Mean
      duration of follow-up was 26 months (range 3 to 71) with 9 late deaths (38%), 6
      in the idiopathic group. The five-year actuarial survival was 74% in the ischemic
      group and 33% in the idiopathic group. The observational analysis of literature
      included a total of 506 patients (425 males, age 50.2 +/- 5.2 years)]. The
      etiology was idiopathic in 255 (50.4%), and ischemic in 89 (17.6%) patients.
      Baseline characteristics of the whole population include: ejection fraction 18.9
      +/- 3.9%, NYHA functional class 3.7 +/- 0.2, and LVEDD of 7.7 +/- 0.4 cm. Severe
      mitral regurgitation was present in 368 (72.7%) patients. There were 88 (17.4%)
      in-hospital deaths. Cause of death included 55 due to (62.5%) low cardiac output,
      10 (11.3%) due to severe bleeding, 7 (7.95%) caused by malignant arrhythmias, 8
      (9%) due to sepsis, and 5 (5.7%) as a result of stroke. Ten of the selected
      series (overall 386 patients) reported late outcome. There were 89 (22.9%) late
      deaths, 12 (13.5%) were not cardiac-related, 50 (56.2%) were due to recurrence of
      congestive heart failure (CHF), 20 (22.5%) caused by sudden arrhythmias, 5 (5.6%)
      due to infections, and 2 (2.2%) from strokes. Overall, there were 248 (64.2%)
      survivors, of whom 179 (72.17%) were reported to be in NYHA functional class I or
      II. All 10 papers reported one-year survival ranging from 50% to 85%. Seven
      reported a two-year survival of 45% to 72%, and 4 reported a three-year survival
      of 33% to 64%. CONCLUSIONS: Our results and the review of the literature seem to
      suggest a relatively high early mortality with satisfactory late results of PLV
      in patients with dilated cardiomyopathy.

PMID- 12809392
TI  - Partial left ventriculectomy (Batista's Procedure) case report: 40 months follow
      up.
AB  - OBJECTIVE: Partial left ventriculectomy (PLV) (also known as Batista's Procedure)
      is a surgical procedure for treatment of dilated cardiomyopathy when cardiac
      transplant is contraindicated. Mitral valve replacement is needed because of
      mitral regurgitation as a consequence of annulus enlargement and papillary muscle
      resection. Bleeding and arrythmias are the main complications. METHODS: We
      considered for this operation a 60-year-old male patient. He suffered from
      valvular dilating cardiomyopathy as a consequence of mitral and aortic valve
      regurgitation. Furthermore, a severe peripheral vascular disease treated with
      aortic-bifemoral prosthesis contraindicated heart transplantation. He needed
      frequent hospital admissions for pulmonary edema and his quality of life was very
      poor. Batista's procedure was performed in March 1998, successfully. Mitral and
      aortic valves were replaced by use of mechanical prosthesis. The postoperative
      period was characterized by early weaning from ventilator and drugs; atrial
      fibrillation, reversed by Amiodaron; a little bilateral pleural effusion; and
      pacemaker implantation following advanced heart conduction block. No bleeding
      episodes were observed. In March 2001 the progression of the vascular disease
      forced the patient to undergo to a femoro-femoral bypass and endoarterectomy of
      the right branch of the vascular prothesis. The patient tolerated the procedure
      very well. He had no complications during the postoperative period with early
      weaning from ventilator and drugs. RESULTS: At the end of the procedure ejection
      fraction raised from 15% to 30%. Echocardiographic data demonstrated a slow but
      progressive improvement of the cardiac diameters and volumes with a preserved
      left ventricular function. CONCLUSION: Even if a larger number of cases and
      longer follow-up are necessary, our report demonstrated that Batista's procedure
      should be considered as a surgical alternative to heart transplantation, in well
      selected patients with absolute contraindication to heart transplantation and
      left ventricular assist device implantation.

PMID- 12809393
TI  - End-stage cardiomyopathy and secondary mitral insufficiency surgical alternative
      with prosthesis implant and left ventricular remodeling.
AB  - Secondary mitral insufficiency is a strong risk factor for death in end-stage
      cardiomyopathies. The possible correction of mitral regurgitation is now being
      accepted as an alternative to cardiac transplantation in a special subset of
      patients. We proposed a new surgical approach that consisted of implantation of a
      mitral prosthesis smaller than the annulus, as well as preservation and traction
      of the papillary muscles to reduce sphericity of the left ventricle. Between
      December 1995 and August 2001, 71 cases were operated on including the following
      etiologies: ischemic (38), idiopathic (29), Chaga's disease (2), viral (1), and
      postpartum (1). All patients were in an end-stage phase with more than two
      hospital admissions in the last three months; seven were in intensive care units
      receiving drugs and intra-aortic balloon counterpulsation, and one was in
      cardiogenic shock. The patients were analyzed according to clinical criteria,
      echocardiographic findings, and morphology of the left ventricle. Hospital
      mortality was 16.9% (12/71) and mid-term follow-up showed evidence of improvement
      in clinical status and some echocardiographic parameters. This technique, despite
      a high mortality rate (due to other clinical conditions at the time of surgery),
      offers a promising therapeutic alternative for the treatment of patients in
      refractory heart failure with cardiomyopathy associated with secondary mitral
      regurgitation.

PMID- 12809394
TI  - Use of off-pump and on-pump CABG strategies in current clinical practice: the
      Clinical Outcomes Assessment Program of the state of Washington.
AB  - BACKGROUND: The purpose of this study is to assess clinical outcomes and regional
      differences in the use of on-pump and off-pump CABG in current clinical practice.
      METHODS: Between January 1, 1999, and December 31, 2000, there were 10,429 CABG
      procedures performed in 16 Washington state hospitals, all of which participate
      in Clinical Outcomes Assessment Program database. This analysis excluded patients
      with a history of prior CABG as well as those who underwent emergent surgery.
      After applying these exclusion criteria, 8402 patients (7169 on-pump and 1233 off
      pump CABG procedures) were evaluated and presented as both unadjusted and risk
      adjusted outcomes. OUTCOMES: Off-pump CABG constituted 14.7% of all surgical
      revascularization procedures. These varied enormously among individual centers
      from an incidence of 0% to 68.9%. The use of off-pump CABG was not associated
      with a decreased risk of risk-adjusted hospital mortality or stroke, but was
      associated with a reduction in hospital stay > 7 days (OR 0.62, CI 0.51-0.76),
      ventilator > 24 hours (OR 0.52, CI 0.34-0.81), dialysis (OR 0.34, CI 0.14-0.86),
      and RBC transfusion (OR 0.5, CI 0.40-0.61). CONCLUSIONS: Despite its highly
      variable use, off-pump CABG seems to be judiciously used in current clinical
      practice in the State of Washington and is associated with a decrease in
      morbidity in appropriately selected patients.

PMID- 12809395
TI  - Effect of timing of chest tube removal on development of pericardial effusion
      following cardiac surgery.
AB  - BACKGROUND: There are no standard criteria for the timing of drain removal. The
      objective of this study was to determine whether the macroscopic appearance of
      chest tube drainage fluid to serosanguineous may be used as a criteria for drain
      removal. METHODS: 2,359 patients were assessed retrospectively and 80 randomized
      patients were followed prospectively who underwent cardiac surgery. In both parts
      of the study, patients were divided into two groups according to the timing of
      drain removal. Group I consisted of patients whose chest tubes were removed as
      soon as the macroscopic appearance of the drainage fluid turned to
      serosanguineous. Group II consisted of patients whose chest tubes were removed at
      the second postoperative day when the drainage output declined to less than 50 mL
      in a five-hour period. In the retrospective part, cases of hemodynamically
      significant pericardial effusion observed within seven days postoperatively were
      reviewed. In the prospective part, just before the drain removal, the fluid
      sample hematocrit obtained from the drain lines and patients' blood hematocrit
      were measured and recorded. Patients were evaluated with echocardiography for
      pericardial effusion. RESULTS: No statistically significant difference was
      detected in the frequency of hemodynamically significant pericardial effusion and
      incidence or amount of pericardial effusion between the two study groups. The
      drain hematocrit to blood hematocrit ratios before drain removal showed a
      significant correlation with pericardial effusion. The strength of correlation
      between the drain hematocrit to blood hematocrit ratios before drain removal and
      pericardial effusion was also studied using receiver operating characteristic
      curve, which suggests that a drain hematocrit to blood hematocrit ratio of < or =
      0.3 is strongly predictive that pericardial effusion would be absent or mild
      between the fifth and seventh postoperative days. CONCLUSIONS: It is safe to
      remove the chest tubes as soon as the macroscopic appearance of the drainage
      fluid turns to serosanguineous since this practically indicates cessation of
      active bleeding.

PMID- 12809396
TI  - A critical evaluation of results of partial left ventriculectomy.
AB  - BACKGROUND: Because of the variation in the surgical procedures designed to
      reduce ventricular radius, along with differences in hospital care, it is
      difficult to disentangle the factors that may contribute to the success or
      failure of the partial left ventriculectomy. METHODS AND RESULTS: We undertook
      partial left ventriculectomy in 18 patients, 10 suffering from idiopathic dilated
      cardiomyopathy and 8 from ischemic heart disease. We assessed the amount of
      reduction in wall stress, the systolic thickening of the ventricular wall, and
      the extent of connective tissue in the excised segment of the wall. Of the
      overall group, six patients died, three from infarction, one of stroke, one with
      asystole, and one with ventricular fibrillation. The mean decrease in measured
      mesh tension was 40% (p < 0.001). Most patients exhibited improvements
      postoperatively in terms of the systolic thickening of the posterior and superior
      free walls of the left ventricle. In those in whom the events could be monitored,
      life-threatening arrhythmias posed complications in three of four patients with
      ischemic heart disease, and in two of six patients suffering from idiopathic
      dilated cardiomyopathy. In one patient, death was associated with a transmural
      alignment of fibrous tissue. CONCLUSIONS: Our measured reductions in myocardial
      mesh tension were in keeping with the anticipated theoretical reduction in wall
      stress expected from partial ventriculectomy. The basic concept underscoring
      surgical maneuvers to reduce ventricular radius, therefore, is sound. A potential
      trap is the resection of the marginal artery. Critical myofibrosis was a rare
      complication. Arrhythmias, which are common, can successfully be treated by
      implantation of antitachycardic and defibrillatory devices.

PMID- 12809397
TI  - Delayed presentation of injury to the sinus of valsalva with aortic regurgitation
      resulting from penetrating cardiac wounds.
AB  - A 39-year-old man had attempted to commit suicide using a small knife to
      penetrate the anterior chest wall. An emergency operation was performed
      successfully to repair the penetrating cardiac injury of the right ventricular
      outflow tract without using cardiopulmonary bypass. Two years after the
      operation, he was complained of dyspnea and a continuous murmur was detected.
      Echocardiography and cardiac catheterization revealed aorto-right ventricular
      fistula in the sinus of valsalva with aortic regurgitation. In operation, the
      healed laceration of the right coronary cusp and the fistula between aorta and
      right ventricle were identified. The fistula was closed using a Dacron patch and
      the aortic valve was replaced with a mechanical valve. Long-term follow-up of
      penetrating thoracic injuries is important for detecting underlying intracardiac
      lesions.

PMID- 12809398
TI  - Intracardiac left ventricular support in beating heart, multi-vessel
      revascularization.
AB  - BACKGROUND: Less invasive operation procedures without support of extracorporeal
      circulation are becoming increasingly important. A basic requirement for good
      long-term results in such cases is, however, the complete revascularization of
      the affected coronary vessels. The unsatisfactorily high conversion rate from
      bypass operations originally planned as off-pump to conventional operations with
      heart-lung machines, because of the failure to reach the target vessels on the
      rear wall of the heart through hemodynamic instability led to investigation of
      the efficiency of a microaxial pump (Impella elect) placed in the left ventricle.
      METHODS: In a prospective project 15 of 38 consecutive patients selected for
      coronary revascularization with beating heart had a micro pump transaortically
      implanted in the left ventricle to support the heart during the operation with a
      flow rate of 2.5 to 3.9 l/min. RESULTS: With 8 of 23 patients operated on without
      pump support, the operation had to be converted to conventional methods with a
      heart-lung machine. Only one patient out of the left-ventricle-supported group
      had to be further operated on conventionally because of a deep intramyocardial
      positioned left anterior descending coronary artery (LAD) (p < 0.05). The
      investigated laboratory parameters, especially creatine kinase (CK), CK-MB
      isoenzyme, and clotting showed no significant difference. There tended to be a
      higher blood loss recorded with the pump-supported patients. CONCLUSION: In
      summary, it appeared that the application of a left ventricular coaxial pump with
      comparable results seemed to make possible complete revascularization in nearly
      all patients.

PMID- 12809399
TI  - Bilateral pectoral myocutaneous advancement flaps and anatomic sternal wound
      reconstruction in cyanotic infants with mediastinitis.
AB  - OBJECTIVE: The purpose of this study was to assess the results and applicability
      of a modified chest closure technique employing bilateral pectoral myocutaneous
      advancement flaps after sternal re-approximation for postoperative mediastinitis
      in cyanotic infants. METHODS: The study population is of a single surgeon's
      pediatric cardiac experience (n = 253) over a 2-year period. With retrospective
      hospital chart review six cases with deep sternal wound complications were
      identified (five mediastinitis and one hypoxemic wound necrosis). Sternal wound
      reconstruction was done with the above technique in all cases. Follow up was
      completed by outpatient record review and with telephone interviews. RESULTS: All
      six cases presented in this paper were neonates or infants with complex cyanotic
      cardiac malformations. Following chest wall reconstruction all had complete
      resolution of their mediastinitis with no mortality and no wound healing
      complications. Three of them have since undergone elective staged repair, with no
      evidence of residual wound infection. Two babies died during follow-up as a
      result of progressive respiratory compromise. CONCLUSION: For postcardiotomy
      mediastinitis in cyanotic infants we recommend limited debridement and anatomic
      sternal reconstruction supported by bilateral pectoral myocutaneous advancement
      flap closure.

PMID- 12809400
TI  - Simplified technique for patch augmentation and chorda reconstruction of left
      atrioventricular valve in complete atrioventricular septal defect.
AB  - Management of the left AV valve is the most crucial component of the repair of
      complete atrioventricular septal defect (cAVSD). A scarcity or deficiency of
      leaflet tissue may compromise satisfactory repair in a small number of patients
      with cAVSD, especially in patients with a normal karyotype. We describe the case
      of a 44-day-old baby who had cAVSD with severe left atrioventricular valve
      regurgitation due to dysplastic bridging leaflets. The repair was successfully
      performed by augmenting leaflet tissue and reconstructing the chorda using single
      patch. This technique could be one of the options in the repair of valves in
      order to avoid valve replacement in a small infant, although material of patch
      and reoperation need to be considered.

PMID- 12809401
TI  - Perpendicular insertion of Dacron patch for aortoplasty in adult coarctation of
      aorta to increase circular elasticity.
AB  - Circular elasticity cannot be obtained in standard patch aortaplasty in patients
      with coarctation of aorta. We inserted Dacron patch perpendicularly to standard
      fashion. The creases of Dacron patch became parallel to descenden aorta. Circular
      elasticity, that reduces both true and false aneurysm incidence in the long
      termperiod, can be obtained with this modification.

PMID- 12809402
TI  - Repair of partial atrioventricular septal defect through a minimal right vertical
      infra-axillary thoracotomy.
AB  - OBJECTIVE: To report a new minimally invasive and cosmetic approach for partial
      atrioventricular septal defect (PAVSD) repair. METHODS: From November 1997 to
      January 2000, six patients with a mean age of 19.2 +/- 7.7 years underwent
      minimal right vertical infra-axillary thoracotomy for PAVSD repair. Left
      atrioventricular (AV) valve regurgitation was assessed on the beating heart
      before and after valvuloplasty. Commissuroplasty of the left AV valve and atrial
      septum repair were done in all patients. RESULTS: There were no operative or late
      mortality, and no morbidity directly related to the thoracotomy approach. The
      average length of the incision was 8.3 +/- 131 cm. The arrest times averaged 32.8
      +/- 8.3 minutes, and the cardiopulmonary bypass times averaged 66.0 +/- 9.0
      minutes. One patient had a mild to moderate left AV valve regurgitation
      postoperatively. All patients were free of symptoms during the follow-up.
      CONCLUSION: The minimal right vertical infra-axillary thoracotomy is a safer,
      more cosmetic and less invasive approach than median sternotomy for the repair of
      PAVSD.

PMID- 12809403
TI  - Early experience with cardiopulmonary bypass: reflections.

PMID- 12809405
TI  - Tobacco control as a lifetime process.

PMID- 12809404
TI  - Clinical cellular cardiomyoplasty: technical considerations.
AB  - Three patients, all with a history of coronary heart disease, underwent coronary
      artery bypass grafting and implantation of autologous satellite cells. Satellite
      cells were isolated from muscle biopsies of the right vastus lateralis muscle
      after enzymatic treatment. While the heart was still under hypothermic
      cardioplegia, 4 mL of cell suspension divided into approximately 40 doses was
      injected into the ventricular wall of the ischemic area. Less than 5 minutes were
      required to complete the cell implantation. All patients survived the procedure,
      without obvious arrhythmia, had an uneventful recovery, and were discharged from
      the hospital. At 3 to 4 months follow-up examination, increased left ventricular
      ejection fraction, decreased left ventricular diastolic diameter, as well as
      improved ventricular wall thickness and perfusion at the satellite cell
      implantation sites were observed. Our experience indicated the safety and early
      benefit of cellular cardiomyoplasty using autologous satellite cells.

PMID- 12809406
TI  - Oncologists disagree on impact of patient internet use.

PMID- 12809407
TI  - Breast cancer screening: a final analysis?

PMID- 12809408
TI  - American Cancer Society guidelines for breast cancer screening: update 2003.
AB  - In 2003, the American Cancer Society updated its guidelines for early detection
      of breast cancer based on recommendations from a formal review of evidence and a
      recent workshop. The new screening recommendations address screening mammography,
      physical examination, screening older women and women with comorbid conditions,
      screening women at high risk, and new screening technologies.

PMID- 12809409
TI  - Finding breast cancer early.

PMID- 12809410
TI  - Ongoing care of patients after primary treatment for their cancer.
AB  - Nearly nine million people living in the United States have had a diagnosis of
      cancer. As the population ages, this number will increase. Most of these people
      will need follow-up care to deal with problems related to their cancer. Depending
      on the cancer, they may or may not benefit from surveillance to detect
      recurrence. Most will be more likely than average to develop a second primary
      cancer. Some will be genetically susceptible to another type of cancer. Many will
      have complications from their treatment that need attention. Also, their
      treatment may have altered certain physiologic functions. Finally, many will have
      suffered psychosocial difficulties either as a result of their cancer or its
      treatment. This article deals with these issues for the most commonly encountered
      cancers. Its major goal is to alert physicians to be aware of and help them to
      deal with these issues. Clearly, such an ambitious goal can only be partly
      achieved in a single journal article. Hopefully, the references included will
      allow physicians to proceed further if they wish.

PMID- 12809411
TI  - Do we need a checklist for reporting the results of diagnostic test evaluations?
      The STARD proposal.

PMID- 12809412
TI  - Factors predicting successful needle-localized breast biopsy.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to identify factors that
      predict successful removal of nonpalpable breast lesions with mammography-guided
      needle-localized breast biopsy. MATERIALS AND METHODS: Of the 455 consecutive
      patients referred for needle-localized breast biopsy of one or more nonpalpable
      breast lesions between January 1990 and December 1994, 272 (59.8%) had
      sufficiently complete data to be included in this study. Medical charts,
      pathology laboratory reports, wire-placement mammograms, and radiographs of
      specimens from each patient were retrospectively reviewed to evaluate the effect
      of the following factors on the success of the procedure: distance from the
      lesion to the localizing wire, breast density, breast size, specimen volume, and
      lesion volume. All radiographs were independently evaluated by two radiologists
      who are experts in breast imaging. RESULTS: Needle-localized breast biopsy was
      successful in 254 (93.3%) of 272 lesions. Placement of the localization wire
      within 5 mm of the breast lesion was a significant predictor of successful lesion
      removal (P = .007). Results from logistic regression analysis showed that needle
      localized breast biopsy failure was associated with increased wire distance (P =
      .0006), decreased breast size (P = .02), and decreased specimen volume (P = .03).
      CONCLUSION: Needle localization wires should be placed within 5 mm of
      mammographically visible lesions to increase the probability of successful lesion
      excision.

PMID- 12809413
TI  - Spatial variation of resolution and noise in multi-detector row spiral CT.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate an
      approach for measuring the variations of three-dimensional spatial resolution and
      image noise throughout a field of view imaged with multi-detector row spiral
      computed tomographic (CT) scanners. MATERIALS AND METHODS: The authors designed a
      phantom (diameter, 320 mm) that contained 37 metallic spheres (diameter,
      approximately 0.8 mm) positioned between two disks made of a material with
      attenuation being that of water. One sphere was located at the isocenter of the
      phantom, and the rest were evenly spaced in three concentric rings with diameters
      of 100, 200, and 300 mm, respectively. The phantom was imaged with two widely
      used multi-detector row CT scanners by using a standard protocol and four
      variations of that protocol. Because a recently developed theory holds that image
      resolution should be proportional to the square root of the trace of the
      covariance matrix of a point spread function, the authors developed a software
      package to segment high-attenuation spheres from the CT image volume and compute
      point spread functions from blurred images of the spheres. Three-dimensional
      spatial resolution and image noise were calculated as a function of radial
      distance within the field of view. RESULTS: Resolution and noise were quantified
      in the resultant CT image volumes and found to be nonisotropic, with worse
      resolution and less noise occurring at the periphery of the field of view.
      CONCLUSION: The method enabled measurement of variations in spatial resolution
      and of their distribution on images obtained with multi-detector row CT scanners.
      These findings may contribute to the development of an improved algorithm for
      image reconstruction.

PMID- 12809414
TI  - T1rho MR imaging of the human wrist in vivo.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was (a) to demonstrate the
      feasibility of computing T1rho maps of, and T1rho dispersion in, human wrist
      cartilage at MR imaging in vivo and (b) to compare T1rho and T2 weighting in
      terms of magnitude of relaxation times and signal intensity contrast. MATERIALS
      AND METHODS: T2 and T1rho magnetic resonance images of wrist joints in healthy
      volunteers (n = 5) were obtained with a spin-echo sequence and a fast spin-echo
      sequence pre-encoded with a spin-lock pulse cluster. A 1.5-T clinical imager was
      used (Signa; GE Medical Systems, Milwaukee, Wis) with a 9.5-cm-diameter transmit
      receive quadrature birdcage coil tuned to 63.75 MHz. RESULTS: T1rho relaxation
      times at a spin-lock frequency of 500 Hz vary from 40.5 msec +/- 0.85 to 56.6
      msec +/- 4.83, and T2 relaxation times vary from 28.1 msec +/- 1.88 to 34.5 msec
      +/- 2.63 (mean +/- standard error of the mean, n = 5, P < .016) in various
      regions of the wrist. T1rho dispersion was observed in the range of spin-lock
      frequencies studied. T1rho-weighted images not only have higher signal-to-noise
      ratios but also show better fluid and fat signal suppression than T2-weighted
      images. CONCLUSION: It was possible to perform T2- and T1rho-weighted MR imaging
      of human wrist cartilage in vivo with standard clinical imagers. The higher
      signal-to-noise ratio and improved contrast between cartilage and surrounding fat
      achieved with T1rho imaging may provide better definition of lesions and accurate
      quantitation of small changes in cartilage degeneration.

PMID- 12809415
TI  - Making cost-effectiveness analyses clinically relevant: the effect of provider
      expertise and biliary disease prevalence on the economic comparison of
      alternative diagnostic strategies.
AB  - RATIONALE AND OBJECTIVES: This study was performed to assess the incremental cost
      effectiveness of initial magnetic resonance cholangiopancreatography (MRCP) and
      initial endoscopic ultrasonography (EUS) compared with initial endoscopic
      retrograde cholangiopancreatography (ERCP) and to evaluate the effect of MRCP
      provider expertise on the relative cost-effectiveness of the three methods.
      MATERIALS AND METHODS: Thirty patients with suspected biliary disease and
      referred for ERCP were prospectively evaluated with EUS, MRCP, or ERCP within 24
      hours of referral, according to institutional review board-approved protocol.
      Performance characteristics were measured for EUS and MRCP, with ERCP as the
      reference standard. A decision analysis compared the clinical and economic
      effects of three diagnostic strategies (ERCP, EUS followed by ERCP [EUS-ERCP],
      and MRCP followed by ERCP [MRCP-ERCP]) using prospective EUS and MRCP test
      characteristics and Medicare reimbursements. The added costs per additional
      correct diagnosis and per additional false-positive finding averted and the rates
      and costs of ERCP-related complications were calculated for EUS-ERCP and MRCP
      ERCP. Two additional MRCP readers reviewed MRCP data to evaluate interobserver
      variability and estimate provider expertise. Additional economic analyses
      incorporated these estimates. RESULTS: Compared with initial ERCP, EUS-ERCP
      demonstrated 72% of biliary abnormalities and reduced ERCP-related complications
      by 60%; the corresponding percentages for MRCP-ERCP were 48% and 40%. Initial EUS
      and initial MRCP decreased the number of ERCP procedures performed by 69% and
      49%, respectively. Each correct diagnosis made with ERCP that would not have been
      made with initial EUS or initial MRCP cost an additional 4,875 dollars or 2,580
      dollars, respectively. Each false-positive diagnosis averted with initial ERCP
      that would have been made with EUS-ERCP or MRCP-ERCP cost an additional 9,750
      dollars or 1,548 dollars, respectively. The decision model was most sensitive to
      disease prevalence. As provider expertise increased, the additional cost of an
      additional correct diagnosis increased for ERCP compared with MRCP-ERCP, with
      disease prevalence accentuating provider effects. CONCLUSION: Initial EUS and
      initial MRCP are less costly than initial ERCP, but provider expertise, biliary
      disease prevalence, and procedural costs influence incremental cost
      effectiveness.

PMID- 12809417
TI  - Measurement of the RT interval on ECG records during electron-beam CT.
AB  - RATIONALE AND OBJECTIVES: The R wave of the electrocardiogram is used widely as a
      trigger for cardiac imaging. This study was designed to determine the optimal
      interval between the R wave and end systole for triggering of electron-beam
      computed tomography (CT) in a group of patients with various heart rates who are
      undergoing assessment for coronary artery calcification. MATERIALS AND METHODS: A
      total of 862 consecutive asymptomatic patients referred for screening with
      electron-beam CT for coronary artery calcification were enrolled in the study.
      Patients' R-R, RT, and PR intervals were measured by using the software of the CT
      console computer. Correlation coefficients were computed and linear regression
      analyses were performed for all intervals measured. Results were analyzed
      according to patient age (three subgroups), sex (two subgroups), and heart rate
      (nine subgroups). Separate formulas for calculating the length of RT intervals in
      men and in women were developed. RESULTS: After correction for heart rate, a
      significant difference was found in mean RT and PR intervals between women and
      men, with the mean intervals in women being longer (P < .001). No significant
      difference was found in these intervals within the three age-defined subgroups (<
      or = 40, 41-60, and >60 years; P > .05). However, significant negative
      correlations were found between heart rates and the lengths of all measured
      intervals. The results of statistical analysis indicate that most of the
      variation in the R-R interval with different heart rates occurred in diastole and
      that the duration of systole was relatively constant. CONCLUSION: For optimal
      cardiac imaging, triggering should take place in late systole, avoiding the RT
      interval variability that occurs in diastole.

PMID- 12809416
TI  - Aortic atherosclerosis detected with electron-beam CT as a predictor of
      obstructive coronary artery disease.
AB  - RATIONALE AND OBJECTIVES: Several studies have demonstrated an association
      between coronary and aortic atherosclerosis. Aortic atherosclerosis is easily
      quantified by means of electron-beam computed tomography (CT). The aim of this
      study was to evaluate the usefulness of measurement of aortic atherosclerosis
      with electron-beam CT as an independent predictor of obstructive coronary artery
      disease (CAD). MATERIALS AND METHODS: Ninety-seven patients (67 men, 30 women;
      mean age, 61 years +/- 12) were enrolled and underwent electron-beam CT with and
      without contrast material. Coronary artery calcification was quantified with
      nonenhanced electron-beam CT by means of Agatston score. CAD was defined as
      luminal narrowing of the coronary artery by at least 70%, as measured with
      electron-beam angiography. Aortic atherosclerosis was quantified by measuring
      raised lesions of the aortic wall (plaque) and wall thickening (volume and
      thickness) in the midportion of the descending thoracic aorta (10 contiguous
      sections), as depicted at contrast material-enhanced CT angiography. RESULTS:
      Aortic plaque and calcification were detected only in patients who were at least
      58 years old. The presence of aortic plaque was predictive of obstructive CAD,
      independent of coronary artery calcification. The sensitivity of aortic plaque
      (raised lesions) for obstructive CAD was 89% in patients at least 58 years old,
      and the specificity was 63%. Aortic calcification had a sensitivity of 56% and a
      specificity of 72% for diagnosis of obstructive CAD. CONCLUSION: This study
      demonstrated that aortic plaque detected with contrast-enhanced electron-beam CT
      was a more consistent predictor of obstructive CAD than other independent aortic
      variables. Aortic calcification depicted on nonenhanced CT images was highly
      specific for obstructive CAD.

PMID- 12809418
TI  - Postsurgical change in the tracheal bifurcation angle after upper lobectomy:
      radiographic evaluation.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate postsurgical
      changes in the tracheal bifurcation angle on chest radiographs after upper
      lobectomy and to determine whether bronchial repositioning after upper lobectomy
      mimics that in upper lobe collapse. MATERIALS AND METHODS: The authors selected
      81 patients who had undergone upper lobectomy with complete mediastinal and
      subcarinal lymph node dissection and in whom chest radiographs had been obtained
      before operation and at four postoperative intervals. The interbronchial angle
      and the subcarinal angle were measured on the preoperative and postoperative
      radiographs and compared statistically. RESULTS: The average interbronchial angle
      and subcarinal angle during any postoperative period were significantly smaller
      than those before lobectomy (P < .001). These average angles decreased gradually
      during the postoperative periods. CONCLUSION: The tracheal bifurcation angle was
      decreased on follow-up chest radiographs in most patients who underwent upper
      lobectomy with mediastinal lymph node dissection. This finding may be useful for
      establishing a history of this surgical procedure on the basis of chest
      radiographs.

PMID- 12809419
TI  - 2003 AUR Joseph E. And Nancy O. Whitley Award. Developing tomorrow's academic
      radiologists: a 3-month residency elective in education.
AB  - RATIONALE AND OBJECTIVES: The shortage of academic radiologists reveals an urgent
      need to attract more residents into academic careers. A great deal of attention
      has been focused on research, but few programmatic initiatives have addressed the
      development of the next generation of radiology educators. The purpose of this
      study was to develop and test a new 3-month residency elective in education.
      MATERIALS AND METHODS: A large academic radiology department developed a 3-month
      education elective, during which two residents would be relieved of clinical
      duties and focus full-time on tasks related to their development as educators,
      including the completion of a major educational project. RESULTS: Two residents,
      in their 3rd year and 4th year of residency, respectively, proposed to
      collaborate in developing a Web-delivered tutorial for the department's senior
      medical student clerkship. At the end of 3 months, their radiology tutorial was
      introduced. In its 1st month, it received a mean rating of 4.3 on a five-point
      scale. The residents stated that the elective had enabled them to develop
      important skills in instructional technology, put into practice their enhanced
      understanding of learning psychology, and substantially strengthened their
      overall commitment to academic careers. CONCLUSION: It is vital that residency
      programs focus on developing the next generation of radiology educators. This
      ongoing education elective represents one successful model.

PMID- 12809420
TI  - Radiology residency eCurriculum developed in-house: evaluation of benefits and
      weaknesses.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate residents'
      use of a radiology curriculum CD-ROM designed to provide ready access to the
      department's curricula, study materials, and Internet resources. MATERIALS AND
      METHODS: A survey questionnaire eliciting feedback about the usability and value
      of the CD-ROM, as well as suggestions for future modifications in its content,
      was distributed to radiology residents (n = 26) in the authors' training program.
      Twenty-three (88%) of the residents responded to the survey. RESULTS: Eighteen
      (78%) of the 23 respondents reported having used the CD-ROM at least once, and 22
      (96%) considered the CD-ROM an asset to the residency program. Fourteen (61%)
      identified the centralization of important information as the greatest benefit of
      the CD-ROM. Nonetheless, a majority continued to rely on more traditional methods
      of obtaining information essential to their work and studies. Twelve (52%) of the
      23 residents reported that daily use of the material stored on the CD-ROM would
      be encouraged by placing it on a departmental intranet, while seven (30%)
      preferred the addition of dedicated computers and the provision of study space in
      the department. CONCLUSION: The CD-ROM has not been fully integrated into the
      residency program. The greatest obstacle to its use is the lack of computer
      resources in the department.

PMID- 12809422
TI  - Sensitivity and specificity should be de-emphasized in diagnostic accuracy
      studies.

PMID- 12809421
TI  - Toward complete and accurate reporting of studies of diagnostic accuracy: the
      STARD initiative.
AB  - RATIONALE AND OBJECTIVES: To comprehend the results of diagnostic accuracy
      studies, readers must understand the design, conduct, and analysis of such
      studies. The authors sought to develop guidelines for improving the accuracy and
      completeness of reporting of studies of diagnostic accuracy in order to allow
      readers better to assess the validity and generalizability of study results.
      MATERIALS AND METHODS: The Standards for Reporting of Diagnostic Accuracy group
      steering committee searched the literature to identify publications on the
      appropriate conduct and reporting of diagnostic studies and to extract potential
      guidelines for authors and editors. An extensive list of items was prepared.
      Members of the steering committee then met for 2 days with other researchers,
      editors, methodologists, statisticians, and members of professional organizations
      to develop a checklist and a prototypical flowchart to guide authors and editors
      of studies of diagnostic accuracy. RESULTS: The search for published guidelines
      on diagnostic research yielded 33 previously published checklists, from which the
      group produced an initial list of 75 items. This list was honed to 25 key items
      by group consensus and on the basis of published research on bias. A prototypical
      flowchart was developed as a tool for conveying information about the method of
      patient recruitment, the order of test execution, and the numbers of patients
      undergoing the test under evaluation, the reference test, or both. Potential
      users reviewed the conference version of the checklist and flowchart and provided
      additional suggestions, which were then incorporated. CONCLUSION: Use of these
      carefully developed, consensus-based guidelines should enable clearer and more
      complete reporting of studies of diagnostic accuracy, as well as better reader
      understanding of the validity and generalizability of study results.

PMID- 12809423
TI  - Automatic registration of MR and SPECT images for treatment planning in prostate
      cancer.
AB  - RATIONALE AND OBJECTIVES: To aid in surgical and radiation therapy planning for
      prostate adenocarcinoma, a general-purpose automatic registration method that is
      based on mutual information was used to align magnetic resonance (MR) images and
      single photon emission computed tomographic (SPECT) images of the pelvis and
      prostate. MATERIALS AND METHODS: The authors assessed the effects of various
      factors on alignment between pairs of MR and SPECT images, including the use of
      particular pulse sequences in MR imaging, image voxel intensity scaling, the use
      of different regions on the MR-SPECT histogram, spatial masking of nonoverlapping
      visual data between images, and multiresolution optimization. A mutual
      information algorithm was used as the cost function for automatic registration.
      Automatic registration was deemed acceptable when it resulted in a transformation
      with less than 2 voxel units (6 mm) difference in translation and less than 2
      degree difference in rotation from that obtained with manual registration
      performed independently by nuclear medicine radiologists. RESULTS: Paired sets of
      MR and SPECT image volumes from four of five patients were successfully
      registered. For successful registration, MR images must be optimal and
      registration must be performed at full spatial resolution and at the full
      intensity range. Masking, cropping, and the normalization of mutual information,
      used to register partially overlapping MR-SPECT volumes, were not successful.
      Multiresolution optimization had little effect on the accuracy and speed of the
      registration. CONCLUSION: Automatic registration between MR and SPECT images of
      the pelvis can be achieved when data acquisition and image processing are
      performed properly. It should prove useful for prostate cancer diagnosis,
      staging, and treatment planning.

PMID- 12809424
TI  - Is terminology used effectively to convey diagnostic certainty in radiology
      reports?
AB  - RATIONALE AND OBJECTIVES: This study was performed to assess the extent of
      agreement among radiologists and nonradiologists in perception of diagnostic
      certainty conveyed by words and phrases commonly used in radiology reports.
      MATERIALS AND METHODS: The study was performed in a large academic radiology
      department. To determine the commonly used terminology for conveying diagnostic
      certainty in radiology reports, 12 randomly selected radiologists from six
      different subspecialties were interviewed. The authors identified the 15 most
      commonly used words and phrases and included these in random order in a
      questionnaire sent to all staff radiologists (n = 45) and to 158 referring
      physicians. Physicians were asked to rank the 15 phrases in order of the
      diagnostic certainty conveyed by each, from 1 (most certain) to 15 (least
      certain), using each number only once. The kappa statistic was used to assess
      agreement in rank order among physicians. RESULTS: The questionnaire response
      rate was 76% (n = 34) for radiologists and 49% (n = 78) for nonradiologists.
      There was excellent agreement among radiologists (kappa = 0.95) and
      nonradiologists (kappa = 0.93) in the rank order for the phrase diagnostic of.
      Although there was good agreement (kappa = 0.45) among radiologists for the word
      unlikely, agreement among nonradiologists was poor (kappa = 0.27). There was very
      poor agreement among all physicians for the rank order of the other 13 phrases.
      CONCLUSION: Among radiologists and nonradiologists, concordance was poor
      regarding the diagnostic certainty associated with phrases commonly used in
      radiology reports. Because poor agreement could lead to suboptimal quality of
      care, the standardization of terminology would benefit all parties.

PMID- 12809425
TI  - The double-edged sword.

PMID- 12809426
TI  - Chest radiography as the comparison for spiral CT in the National Lung Screening
      Trial.

PMID- 12809427
TI  - Inorganics and hormesis.
AB  - The article is a comprehensive review of the occurrence of hormetic dose-response
      relationships induced by inorganic agents, including toxic agents, of significant
      environmental and public health interest (e.g., arsenic, cadmium, lead, mercury,
      selenium, and zinc). Hormetic responses occurred in a wide range of biological
      models (i.e., plants, invertebrate and vertebrate animals) for a large and
      diverse array of endpoints. Particular attention was given to providing an
      assessment of the quantitative features of the dose-response relationships and
      underlying mechanisms that could account for the biphasic nature of the hormetic
      response. These findings indicate that hormetic responses commonly occur in
      appropriately designed experiments and are highly generalizeable with respect to
      biological model responses. The hormetic dose response should be seen as a
      reliable feature of the dose response for inorganic agents and will have an
      important impact on the estimated effects of such agents on environmental and
      human receptors.

PMID- 12809428
TI  - Chemotherapeutics and hormesis.
AB  - This article represents the first comprehensive assessment of hormetic effects of
      chemotherapeutic agents. Hormetic dose-response relationships were reported for a
      wide range of chemotherapeutics, including antibiotics, antiviral, and antitumor
      agents as well as substances that affect hair growth, prostate function,
      cognitive performance, and numerous other endpoints. Particular attention was
      given to assessing the quantitative features of the dose response, the underlying
      mechanistic features of the biphasic nature of the dose response, and the
      clinical implications of hormetic responses. Recognition of the hormetic-like
      biphasic nature of the dose response is expected to have an important impact on
      the design of experiments to assess chemotherapeutics and how such agents may be
      employed more successfully in clinical applications.

PMID- 12809429
TI  - Peptides and hormesis.
AB  - The article provides a broad assessment of the occurrence of hormetic-like
      biphasic dose-response relationships by over 30 peptides representing many major
      peptide classes. These peptide-induced biphasic dose responses were observed to
      occur in a extensive range of tissues, affecting an diverse range of biological
      endpoints. Despite diversity of peptides, models and endpoints, the quantitative
      features of the biphasic dose responses are remarkably similar with respect to
      the amplitude and width of the stimulatory response. These findings strongly
      suggest that hormetic-like biphasic dose responses represent a broadly
      generalizable biological phenomenon.

PMID- 12809430
TI  - Ethanol and hormesis.
AB  - This article provides a detailed assessment of the toxicological and
      pharmacological literature concerning alcohol-induced biphasic dose-response
      relationships. The assessment reveals that alcohol-induced hormetic-like dose
      response relationships are commonly observed, highly generalizeable according to
      model and endpoint and quantitative feature of the dose response. These findings
      have important implications affecting study design, animal model, and endpoint
      selection as well as clinical applications.

PMID- 12809431
TI  - A NIEHS-oriented perspective on hormesis.

PMID- 12809432
TI  - On radiation hormesis expressed in the immune system.
AB  - Radiation hormesis is reviewed with emphasis on its expression in the immune
      system. The shape of the dose-response relationship of the immune functions
      depends on a number of factors, chiefly the target cell under study, experimental
      design with emphasis on the dose range, dose spacing, dose rate and temporal
      changes, as well as the animal strain. For mouse and human T lymphocyte functions
      in the dose range of 0.01 to 10 Gy a J or inverted J-shaped curve is usually
      observed. For the more radioresistant macrophages, stimulation of many of their
      functions is often observed in the dose range up to a few grays. The cellular and
      molecular mechanisms of the enhancement of immunity induced by low-dose radiation
      were analyzed on the basis of literature published in the last decade of the past
      century. Intercellular reactions among the APCs and lymphocytes via distinct
      changes in expression of relevant surface molecules and secretion of regulatory
      cytokines in response to different doses of radiation were described. The major
      signal transduction pathways activated in response to these intercellular
      reactions were illustrated. The suppressive effect of low-dose radiation on
      cancer induction, growth, and metastasis and its immunologic mechanisms were
      analyzed. The present status of research in this field gives strong support to
      radiation hormesis in immunity with low-dose radiation as one of the mechanisms
      of cancer surveillance. Further research with new techniques using microarray
      with biochips to fully elucidate the molecular mechanisms is suggested.

PMID- 12809433
TI  - Metabolic efficiency in response to environmental agents predicts hormesis and
      invalidates the linear no-threshold premise: ionizing radiation as a case study.
AB  - Hormesis derives from high metabolic efficiency and hence high fitness that
      evolve in response to single and multiple environmental agents in low to moderate
      stress habitats. Consequently, nonlinear fitness continua are an evolutionary
      expectation for all environmental agents, which invalidates the LNT premise. For
      ionizing radiation, hormesis is interpreted to be adaptation to background
      radiation exposures, combined with adaptation to higher radiation exposures
      dependent on metabolic protection from the array of other abiotic stresses in the
      environment. This model of radiation hormesis renders suggestions of therapeutic
      radiation supplementation redundant because of similar health effects from other
      environmental agents. Furthermore, the model is compatible with a return of
      exposure levels for radiation protection to higher doses than are presently
      permissible, a deduction with substantial economic benefits.

PMID- 12809434
TI  - Scientific foundations of hormesis. Part 2. Maturation, strengths, limitations,
      and possible applications in toxicology, pharmacology, and epidemiology.
AB  - The notion of hormesis has undergone numerous modifications in the course of the
      20th century. Because of its unfortunate association with homeopathy, hormesis
      did not gain acceptance among biomedical professionals. The lack of a plausible
      mechanism for its occurrence may have contributed much to the rejection of this
      concept. This treatise outlines the conceptual struggle for an understanding of
      the widespread occurrence of low dose effects that appear to be opposite to those
      caused by high doses as also seen in hormesis. An incomplete conceptualization of
      time as a fundamental variable of effects (in addition to dose) is identified as
      one of the major reasons why hermetic responses were not observed more frequently
      than was reported by Calabrese and Baldwin. The definition of hormesis as an
      (over)compensation response to an inhibitory signal lacks a designation for
      (over)compensation responses to stimulatory signals in the other direction.
      Hormoligosis, which was coined by Luckey for all low-dose stimulatory responses
      of toxins, is suggested as a suitable term for generalizing the latter types of
      effects. Both types of effects are recognized as originating in a homeostatic
      overcompensation response that optimizes the ability of an organism to meet
      challenges beyond the limits of normal (unexercised) adaptation. Thus, repeated
      biochemical/physiologic/immunological, etc. exercises like physical exercise make
      an organism more fit and hence both hormetic and hormoligotic effects will have
      life-prolonging consequences. A more complete generalization was developed by
      linking hormesis/hormoligosis with the vast literature on Selye's general
      adaptation syndrome to stress. According to this broader view, stress is just one
      type of homeostatic exercise making organisms more fit for future
      biochemical/physiological/immunological, etc.challenges. Therefore, both hormesis
      and hormoligosis are manifestations of two nonmutational evolutionary principles-
      homeostasis and optimization.

PMID- 12809435
TI  - A mechanism for hormesis--a problem in the wrong discipline.
AB  - The wealth of examples of hormesis exhibiting the beta curve leave little doubt
      as to the generality of the phenomenon. However, its full acceptance requires a
      satisfactory theoretical basis to account for the diversity of instances of
      hormesis; without it the concept has little meaning beyond what is obvious from
      the defining beta curve. It has been proposed that a homeostatic hypothesis is
      the most plausible and is gaining support. However, there is a need to involve
      researchers in other disciplines than toxicology to identify physiological
      mechanisms to account for it, whereupon hormesis can begin to gain wider
      recognition and fulfill its potential in pure and applied science.

PMID- 12809450
TI  - Diagnostic strategies for excluding pulmonary embolism in clinical outcome
      studies. A systematic review.
AB  - BACKGROUND: Pulmonary embolism is a common clinical disorder that is associated
      with high morbidity and mortality if untreated. It is important to confirm or
      rule out the diagnosis in patients with clinical suspicion of the disease.
      PURPOSE: To evaluate various diagnostic strategies for excluding pulmonary
      embolism. DATA SOURCES: MEDLINE (1966 to February 2003), EMBASE, and DARE; study
      investigators; and reference lists. STUDY SELECTION: Prospective clinical outcome
      studies. DATA EXTRACTION: The researchers recorded the frequency of symptomatic
      venous thromboembolism over 3 months of follow-up in patients in whom pulmonary
      embolism had been excluded according to various strategies. Strategies were
      divided into three categories according to the number of rounds of diagnostic
      tests needed to exclude pulmonary embolism. DATA SYNTHESIS: 25 studies involving
      more than 7000 patients were included. In all referred patients, two strategies
      normal results on pulmonary angiography or lung scintigraphy and normal d -dimer
      levels combined with low clinical probability-safely excluded pulmonary embolism
      (failure rates < or = 3%). In the second round of diagnostic tests, in patients
      who had had a nondiagnostic lung scan, both pulmonary angiography and serial leg
      testing for venous thrombosis were accurate and safe. When d -dimer testing
      combined with clinical probability was inconclusive, a normal perfusion lung scan
      safely excluded pulmonary embolism. Accumulating evidence shows that normal
      results on spiral computed tomography may also safely exclude the disease.
      CONCLUSIONS: Many diagnostic strategies to exclude pulmonary embolism have been
      evaluated in consecutive patients. Interest is likely to increase in a simple,
      fast strategy, starting with a normal perfusion lung scan or a combination of
      normal d -dimer levels and low clinical probability. After the initial round of
      testing, a reliable diagnostic method, such as angiography or lung scintigraphy,
      is warranted.

PMID- 12809451
TI  - Glimepiride combined with morning insulin glargine, bedtime neutral protamine
      hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A
      randomized, controlled trial.
AB  - BACKGROUND: Patients with type 2 diabetes are often treated with oral
      antidiabetic agents plus a basal insulin. OBJECTIVE: To investigate the efficacy
      and safety of glimepiride combined with either morning or bedtime insulin
      glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with
      type 2 diabetes. DESIGN: Open-label, randomized, controlled trial. SETTING: 111
      centers in 13 European countries. PATIENTS: 695 patients with type 2 diabetes who
      were previously treated with oral antidiabetic agents. INTERVENTION:
      Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or
      bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The
      insulin dose was titrated by using a predefined regimen to achieve fasting blood
      glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL). MEASUREMENTS:
      Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight.
      RESULTS: Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to 
      1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with
      bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH
      insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin
      glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime
      insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point
      fasting blood glucose levels improved similarly in all three groups. Nocturnal
      hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and
      bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin
      (89 of 232 patients [38%]) (P < 0.001). CONCLUSION: The risk for nocturnal
      hypoglycemia was lower with glimepiride in combination with morning and bedtime
      insulin glargine than with glimepiride in combination with bedtime NPH insulin in
      patients with type 2 diabetes. Morning insulin glargine provided better glycemic
      control than did bedtime insulin glargine or bedtime NPH insulin.

PMID- 12809452
TI  - Cost-effectiveness of vaccination against invasive pneumococcal disease among
      people 50 through 64 years of age: role of comorbid conditions and race.
AB  - BACKGROUND: Guidelines are increasingly recommending preventive services starting
      at 50 years of age, and policymakers are considering such a recommendation for
      pneumococcal polysaccharide vaccination. The finding that pneumococcal
      vaccination is cost-saving for people 65 years of age or older raises the
      question of the vaccination's implications for other older adults, especially
      black people, whose disease incidence exceeds that of nonblack people, and those
      with high-risk conditions. OBJECTIVE: To assess the implications of vaccinating
      black and nonblack people 50 through 64 years of age against invasive
      pneumococcal disease. DESIGN: Cost-effectiveness analysis. DATA SOURCES:
      Published literature for vaccination effectiveness and cost estimates; data on
      disease incidence and case-fatality rates from the Centers for Disease Control
      and Prevention. TARGET POPULATION: Hypothetical cohort 50 through 64 years of age
      with the 1995 U.S. age distribution. TIME HORIZON: Lifetime. PERSPECTIVE:
      Societal. INTERVENTION: Pneumococcal polysaccharide vaccination compared with no
      vaccination. OUTCOME MEASURES: Incremental medical costs and health effects, in
      quality-adjusted life-years per vaccinee. RESULTS OF BASE-CASE ANALYSIS:
      Vaccination saved medical costs and improved health among high-risk black people
      (27.55 dollars savings per vaccinee) and nonblack people (5.92 dollars savings
      per vaccinee), excluding survivors' future costs. For low-risk black and nonblack
      people and the overall general population, vaccination cost 2477 dollars, 8195
      dollars, and 3434 dollars, respectively, to gain 1 year of healthy life. RESULTS
      OF SENSITIVITY ANALYSIS: Excluding survivors' future costs, in the general
      immunocompetent population, cost per quality-adjusted life-year in global worst
      case results ranged from 21 513 dollars for black people to 68 871 dollars for
      nonblack people; in the high-risk population, cost ranged from 11 548 dollars for
      black people to 39 000 dollars for nonblack people. In the global best case,
      vaccination was cost-saving for black and nonblack people in the general
      immunocompetent and high-risk populations, excluding survivors' future costs. The
      cost-effectiveness range was narrower in probabilistic sensitivity analyses, with
      95% probabilistic intervals ranging from cost-saving to 1594 dollars for black
      people and from cost-saving to 12 273 dollars for nonblack people in the general
      immunocompetent population. Costs per quality-adjusted life-year for low-risk
      people with case-fatality rates from 1998 were 2477 dollars for black people and
      8195 dollars for nonblack people, excluding survivors' medical costs.
      CONCLUSIONS: These results support the current recommendation to vaccinate high
      risk people and provide useful information for considering extending the
      recommendation to the general population 50 through 64 years of age. Lack of
      evidence about the effectiveness of revaccination for people 65 years of age or
      older, when disease risks are higher, argues for further research to guide
      vaccination policy.

PMID- 12809454
TI  - Error, blame, and the law in health care--an antipodean perspective.
AB  - Patients are frequently harmed by problems arising from the health care process
      itself. Addressing these problems requires understanding the role of errors,
      violations, and system failures in their genesis. Problem-solving is inhibited by
      a tendency to blame those involved, often inappropriately. This has been
      aggravated by the need to attribute blame before compensation can be obtained
      through tort and the human failing of attributing blame simply because there has
      been a serious outcome. Blaming and punishing for errors that are made by well
      intentioned people working in the health care system drives the problem of
      iatrogenic harm underground and alienates people who are best placed to prevent
      such problems from recurring. On the other hand, failure to assign blame when it
      is due is also undesirable and erodes trust in the medical profession.
      Understanding the distinction between blameworthy behavior and inevitable human
      errors and appreciating the systemic factors that underlie most failures in
      complex systems are essential for the response to a harmed patient to be
      informed, fair, and effective in improving safety. It is important to meet
      society's needs to blame and exact retribution when appropriate. However, this
      should not be a prerequisite for compensation, which should be appropriately
      structured, fair, timely, and, ideally, properly funded as an intrinsic part of
      health care and social security systems.

PMID- 12809453
TI  - Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic
      obstructive pulmonary disease. A meta-analysis.
AB  - BACKGROUND: There is no consensus on the effectiveness of inhaled corticosteroids
      for the treatment of chronic obstructive pulmonary disease (COPD). PURPOSE: To
      evaluate the long-term effects of inhaled corticosteroids on the rate of FEV1
      decline in patients with COPD. DATA SOURCES: MEDLINE, EMBASE, CISCOM, and AMED
      databases and the Cochrane Library (1966 to December 2002), reference lists from
      identified articles, and consultation with experts. Searches were not limited to
      the English language. STUDY SELECTION: Randomized, placebo-controlled trials that
      examined the rate of FEV1 decline as a primary outcome in patients with COPD.
      DATA EXTRACTION: Two reviewers independently extracted the data by using
      predetermined criteria. DATA SYNTHESIS: For the six studies that met the
      inclusion criteria, the summary estimate for the difference in FEV1 decline
      between the placebo and treatment groups was -5.0 +/- 3.2 mL/y (95% CI, -11.2 to
      1.2 mL/y; P = 0.11). CONCLUSIONS: The use of inhaled corticosteroids was not
      associated with the rate of FEV1 decline in 3571 patients followed for 24 to 54
      months.

PMID- 12809455
TI  - A physiologic approach to diagnosis of the Cushing syndrome.

PMID- 12809456
TI  - Zen and the art of physician autonomy maintenance.
AB  - The miracles of scientific medicine propelled physicians to an unparalleled level
      of clinical autonomy during the 20th century. During the past 20 years, physician
      autonomy has been declining, in part because the public has become aware that
      physicians are not consistently applying all of the science they know. One of
      medicine's most cherished professional values, individual clinical autonomy, is
      an important cause of the sometimes suboptimal performance in the timely and
      consistent application of clinical science; thus, it contributes to the decline
      in overall professional autonomy. This paper calls for physicians to practice the
      science of medicine as a profession so that society will allow physicians to
      continue practicing the art of medicine as individual professionals. In a Zen
      like paradox, physicians must give up autonomy in order to regain it.

PMID- 12809457
TI  - Improving patient care.

PMID- 12809458
TI  - Patient safety and the reliability of health care systems.

PMID- 12809459
TI  - A need to update and revise the pneumococcal vaccine recommendations for adults.

PMID- 12809460
TI  - Inhaled corticosteroids and chronic obstructive pulmonary disease: are we barking
      up the wrong tracheobronchial tree?

PMID- 12809461
TI  - The sustenance of teaching.

PMID- 12809462
TI  - A road less traveled.

PMID- 12809464
TI  - The relative safety of ephedra compared with other herbal products.

PMID- 12809465
TI  - Statin-associated myopathy with normal creatine kinase levels.

PMID- 12809466
TI  - Statin-associated myopathy with normal creatine kinase levels.

PMID- 12809467
TI  - Statin-associated myopathy with normal creatine kinase levels.

PMID- 12809468
TI  - Statin-associated myopathy with normal creatine kinase levels.

PMID- 12809470
TI  - The In-Training Examination in Internal Medicine.

PMID- 12809471
TI  - The In-Training Examination in Internal Medicine.

PMID- 12809473
TI  - The In-Training Examination in Internal Medicine.

PMID- 12809474
TI  - Fish oil therapy in recurrent IgA nephropathy.

PMID- 12809476
TI  - Physicians contribute professional expertise worldwide.

PMID- 12809477
TI  - Summaries for patients. Excluding pulmonary embolism safely.

PMID- 12809478
TI  - Summaries for patients. Inhaled steroids for chronic obstructive lung disease.

PMID- 12809479
TI  - Summaries for patients. Cost-effectiveness of pneumococcal vaccine for people 50
      through 64 years of age.

PMID- 12809480
TI  - Summaries for patients. A comparison of three insulin regimens (morning glargine,
      bedtime glargine, or bedtime neutral protamine Hagedorn) in addition to a pill
      for treating type 2 diabetes.

PMID- 12809481
TI  - Simvastatin.

PMID- 12809482
TI  - Biochemistry and structural DNA nanotechnology: an evolving symbiotic
      relationship.
AB  - Structural DNA nanotechnology is derived from naturally occurring structures and
      phenomena in cellular biochemistry. Motifs based on branched DNA molecules are
      linked together by sticky ends to produce objects, periodic arrays, and
      nanomechanical devices. The motifs include Holliday junction analogues, double
      and triple crossover molecules, knots, and parallelograms. Polyhedral catenanes,
      such as a cube or a truncated octahedron, have been assembled from branched
      junctions. Stiff motifs have been used to produce periodic arrays, containing
      topographic features visible in atomic force microscopy; these include
      deliberately striped patterns and cavities whose sizes can be tuned by design.
      Deliberately knotted molecules have been assembled. Aperiodic arrangements of DNA
      tiles can be used to produce assemblies corresponding to logical computation.
      Both DNA structural transitions and branch migration have been used as the basis
      for the operation of DNA nanomechanical devices. Structural DNA nanotechnology
      has been used in a number of applications in biochemistry. An RNA knot has been
      used to establish the existence of RNA topoisomerase activity. The sequence
      dependence of crossover isomerization and branch migration at symmetric sites has
      been established through the use of symmetric immobile junctions. DNA
      parallelogram arrays have been used to determine the interhelical angles for a
      variety of DNA branched junctions. The relationship between biochemistry and
      structural DNA nanotechnology continues to grow.

PMID- 12809483
TI  - ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a
      cytoplasmic tail that interacts with proteins related to signal transduction
      pathways.
AB  - In 1997, McCormick and co-workers identified a novel putative tumor suppressor
      gene, designated ST7, encoding a unique protein with transmembrane receptor
      characteristics [Qing et al. (1999) Oncogene 18, 335-342]. Using degenerate
      primers corresponding to the highly conserved region of the ligand-binding
      domains of members of the low-density lipoprotein receptor (LDLR) superfamily,
      Ishii et al. [Genomics (1998) 51, 132-135] discovered a low-density lipoprotein
      receptor-related protein (LRP) that closely resembles ST7. Later, another LRP
      closely resembling ST7 and LRP3 was found (murine LRP9) [Sugiyama et al. (2000)
      Biochemistry 39, 15817-15825]. These results strongly suggested that ST7 was also
      a novel member of the low-density lipoprotein receptor superfamily. Proteins of
      this superfamily have been shown to function in endocytosis and/or signal
      transduction. To evaluate the relationship of ST7 to the LDLR superfamily
      proteins and to determine whether ST7 may function in endocytosis and/or signal
      transduction, we used proteomic tools to analyze the functional motifs present in
      the protein. Our results indicate that ST7 is a member of a subfamily of the LDLR
      superfamily and that its cytoplasmic domain contains several motifs implicated in
      endocytosis and signal transduction. Use of the yeast two-hybrid system to
      identify proteins that associate with ST7's cytoplasmic domain revealed that this
      domain interacts with three proteins involved in signal transduction and/or
      endocytosis, viz., receptor for activated protein C kinase 1 (RACK1), muscle
      integrin binding protein (MIBP), and SMAD anchor for receptor activation (SARA),
      suggesting that ST7, like other proteins in the LDLR superfamily, functions in
      these two pathways. Clearly, ST7 is an LRP, and therefore, it should now be
      referred to as LRP12.

PMID- 12809485
TI  - Spectroscopic characterization of soybean lipoxygenase-1 mutants: the role of
      second coordination sphere residues in the regulation of enzyme activity.
AB  - Lipoxygenases are non-heme iron enzymes, which catalyze the stereo- and
      regiospecific hydroperoxidation of unsaturated fatty acids. Spectroscopic studies
      on soybean lipoxygenase have shown that the ferrous form of the enzyme is a
      mixture of five- and six-coordinate species (40 and 60%, respectively). Addition
      of substrate leads to a purely six-coordinate form. A series of mutations in the
      second coordination sphere (Q697E, Q697N, Q495A, and Q495E) were generated, and
      the structures of the mutants were solved by crystallography [Tomchick et al.
      (2001) Biochemistry 40, 7509-7517]. While this study clearly showed the
      contribution of H-bond interactions between the first and the second coordination
      spheres in catalysis, no correlation with the coordination environment of the
      Fe(II) was observed. A recent study using density-functional theory [Lehnert and
      Solomon (2002) J. Biol. Inorg. Chem. 8, 294-305] indicated that coordination
      flexibility, involving the Asn694 ligand, is regulated via H-bond interactions.
      In this paper, we investigate the solution structures of the second coordination
      sphere mutants using CD and MCD spectroscopy since these techniques are more
      sensitive indicators of the first coordination sphere ligation of Fe(II) systems.
      Our data demonstrate that the iron coordination environment directly relates to
      activity, with the mutations that have the ability to form a five-coordinate/six
      coordinate mixture being more active. We propose that the H-bond between the weak
      Asn694 ligand and the Gln697 plays a key role in the modulation of the
      coordination flexibility of Asn694, and thus, is crucial for the regulation of
      enzyme reactivity.

PMID- 12809484
TI  - Functional capabilities of an N-formyl peptide receptor-G(alpha)(i)(2) fusion
      protein: assemblies with G proteins and arrestins.
AB  - G protein-coupled receptors (GPCRs) must constantly compete for interactions with
      G proteins, kinases, and arrestins. To evaluate the interactions of these
      proteins with GPCRs in greater detail, we generated a fusion protein between the
      N-formyl peptide receptor and the G(alpha)(i2) protein. The functional
      capabilities of this chimeric protein were determined both in vivo, in stably
      transfected U937 cells, and in vitro, using a novel reconstitution system of
      solubilized components. The chimeric protein exhibited a cellular ligand binding
      affinity indistinguishable from that of the wild-type receptor and existed as a
      complex, when solubilized, containing betagamma subunits, as demonstrated by
      sucrose density sedimentation. The chimeric protein mobilized intracellular
      calcium and desensitized normally in response to agonist. Furthermore, the
      chimeric receptor was internalized and recycled at rates similar to those of the
      wild-type FPR. Confocal fluorescence microscopy revealed that internalized
      chimeric receptors, as identified with fluorescent ligand, colocalized with
      arrestin, as well as G protein, unlike wild-type receptors. Soluble
      reconstitution experiments demonstrated that the chimeric receptor, even in the
      phosphorylated state, existed as a high ligand affinity G protein complex, in the
      absence of exogenous G protein. This interaction was only partially prevented
      through the addition of arrestins. Furthermore, our results demonstrate that the
      GTP-bound state of the G protein alpha subunit displays no detectable affinity
      for the receptor. Together, these results indicate that complex interactions
      exist between GPCRs, in their unphosphorylated and phosphorylated states, G
      proteins, and arrestins, which result in the highly regulated control of GPCR
      function.

PMID- 12809486
TI  - High-resolution structure of the soluble, respiratory-type Rieske protein from
      Thermus thermophilus: analysis and comparison.
AB  - The structure of the soluble Rieske protein from Thermus thermophilus has been
      determined at a resolution of 1.3 A at pH 8.5 using multiwavelength anomalous
      dispersion (MAD) techniques. This is the first report of a Rieske protein from a
      menaquinone-utilizing organism. The structure shows an overall fold similar to
      previously reported Rieske proteins. A novel feature of this crystal form appears
      to be a shared hydrogen between the His-134 imidazole ring ligated to Fe2 of the
      [2Fe-2S] cluster and its symmetry partner, His-134', one being formally an
      imidazolate anion, Fe2-(His-134)N(epsilon)(-)...H-N(epsilon')(His-134')-Fe2', in
      which crystallographic C(2) axes pass equidistant between
      N(epsilon)...N(epsilon') and normal to the line defined by
      N(epsilon)...N(epsilon'). This provides evidence for a stable, oxidized cluster
      with a His(-) ligand and lends support to a previously proposed mechanism of
      coupled proton and electron transfer. A detailed comparison of the Thermus Rieske
      protein with six other Rieske and Rieske-type proteins indicates: (a) The cluster
      binding domain is tightly conserved. (b) The 3-D structure of the 10 beta-strand
      fold is conserved, even among the most divergent proteins. (c) There is an
      approximately linear relation between acid-pH redox potential and number of H
      bonds to the cluster. (d) These proteins have two faces, one points into the
      larger complex (bc(1), b(6)f, or other), is involved in the proton coupled
      electron transfer function, and is highly conserved. The second is oriented
      toward the solvent and shows wide variation in charge, sequence, length,
      hydrophobicity, and secondary elements in the loops that connect the beta-sheets.

PMID- 12809487
TI  - MauG, a novel diheme protein required for tryptophan tryptophylquinone
      biogenesis.
AB  - The biosynthesis of methylamine dehydrogenase (MADH) from Paracoccus
      denitrificans requires four genes in addition to those that encode the two
      structural protein subunits. None of these gene products have been previously
      isolated. One of these, mauG, exhibits sequence similarity to diheme cytochrome c
      peroxidases and is required for the synthesis of the tryptophan tryptophylquinone
      (TTQ) prosthetic group of MADH. A system was developed for the homologous
      expression of MauG in P. denitrificans. Its signal sequence was correctly
      processed, and it was purified from the periplasmic cell fraction. The protein
      contains two covalent c-type hemes, as predicted from the deduced sequence. EPR
      spectroscopy reveals that the protein as isolated possesses about equal amounts
      of one high-spin heme with axial symmetry and one low-spin heme with rhombic
      symmetry. The low-spin heme contains a major and minor component suggesting a
      small degree of heme heterogeneity. The high-spin heme and the major low-spin
      heme component each exhibit resonances that are atypical of c-type hemes and
      dissimilar to those reported for diheme cytochrome c peroxidases. MauG exhibited
      only very weak peroxidase activity when assayed with either c-type cytochromes or
      o-dianisidine as an electron donor. Fully reduced MauG was shown to bind carbon
      monoxide and could be reoxidized by oxygen. The relevance of these unusual
      properties of MauG is discussed in the context of its role in TTQ biogenesis.

PMID- 12809488
TI  - Effect of tryptophan insertions on the properties of the human group IIA
      phospholipase A2: mutagenesis produces an enzyme with characteristics similar to
      those of the human group V phospholipase A2.
AB  - An important characteristic of the human group IIA secreted phospholipase A(2)
      (IIA PLA(2)) is the extremely low activity of this enzyme with
      phosphatidylcholine (PC) vesicles, mammalian cell membranes, and serum
      lipoproteins. This characteristic is reflected in the lack of ability of this
      enzyme to bind productively to zwitterionic interfaces. Part of the molecular
      basis for this lack of activity is an absence of tryptophan, a residue with a
      known preference for residing in the interfacial region of zwitterionic
      phospholipid bilayers. In this paper we have replaced the eight residues that
      make up the hydrophobic collar on the interfacial binding surface of the enzyme
      with tryptophan. The catalytic and interfacial binding properties of these
      mutants have been investigated, particularly those properties associated with
      binding to and hydrolysis of zwitterionic interfaces. Only the insertion of a
      tryptophan at position 3 or 31 produces mutants that significantly enhance the
      activity of the human IIA enzyme against zwitterionic interfaces and intact cell
      membranes. Importantly, the ability of the enzyme mutants to hydrolyze PC-rich
      interfaces such as the outer plasma membrane of mammalian cells was paralleled by
      enhanced interfacial binding to zwitterionic interfaces. The corresponding double
      tryptophan mutant (V3,31W) displays a specific activity on PC vesicles comparable
      to that of the human group V sPLA2. This enhanced activity includes the ability
      to interact with human embryonic kidney HEK293 cells, previously reported for the
      group V enzyme [Kim, Y. J., Kim, K. P., Rhee, H. J., Das, S., Rafter, J. D., Oh,
      Y. S., and Cho, W. (2002) J. Biol. Chem. 277, 9358-9365].

PMID- 12809489
TI  - Solution structure of human intestinal fatty acid binding protein with a
      naturally-occurring single amino acid substitution (A54T) that is associated with
      altered lipid metabolism.
AB  - The human intestinal fatty acid binding protein (I-FABP) belongs to a family of
      intracellular lipid binding proteins. This 15 kDa protein binds dietary long
      chain fatty acids in the cytosol of enterocytes. A naturally-occurring nucleotide
      polymorphism at codon 54, which produces either an alanine-containing (A54) or a
      threonine-containing (T54) protein, has been identified. These two I-FABP forms
      display differential binding and transport of fatty acids across cells, and their
      alleles are associated with in vivo insulin resistance and/or altered lipid
      metabolism in several human populations. The three-dimensional solution structure
      of the more common A54 form was previously determined in our lab. A direct
      comparison between human A54 and T54 I-FABP has now been performed to help
      elucidate the structural origins of their physiological distinctions. The
      solution structure of T54 I-FABP is highly homologous to that of A54 I-FABP, with
      the same overall three-dimensional fold that includes an antiparallel beta-clam
      motif. Chemical shift differences between the two proteins suggest only minor
      local structural changes within the "portal region" and no significant
      alterations elsewhere. Hence, the slightly stronger binding of fatty acids to T54
      I-FABP does not originate from residues in direct contact with the bound fatty
      acid. Instead, it appears that the larger Thr(54) side chain affects the passage
      of the ligand through the entry portal. Structural details of this portal region
      will be discussed in view of the influence residue 54 exerts on the functional
      properties of human I-FABP.

PMID- 12809490
TI  - Structure of the nuclear factor ALY: insights into post-transcriptional
      regulatory and mRNA nuclear export processes.
AB  - ALY is a ubiquitously expressed nuclear protein which interacts with proteins
      such as TAP that are involved in export of mRNA from the nucleus to the
      cytoplasm, as well as with proteins that bind the T cell receptor alpha gene
      enhancer. ALY has also been shown to bind mRNA and to co-localize in the nucleus
      with components of a multiprotein postsplicing complex that is deposited 20-24
      nucleotides upstream of exon-exon junctions. ALY has a conserved RNA binding
      domain (RBD) flanked by Gly-Arg rich N-terminal and C-terminal sequences. We
      determined the solution structure of the RBD homology region in ALY by nuclear
      magnetic resonance methods. The RBD motif in ALY has a characteristic
      beta(1)alpha(1)beta(2)-beta(3)alpha(2)beta(4) fold, consisting of a beta sheet
      composed of four antiparallel beta strands and two alpha helices that pack on one
      face of the beta sheet. As in other RBD structures, the beta sheet has an exposed
      face with hydrophobic and charged residues that could modulate interactions with
      other molecules. The loop that connects beta strands 2 and 3 is in intermediate
      motion in the NMR time scale, which is also characteristic of other RBDs. This
      loop presents side chains close to the exposed surface of the beta sheet and is a
      primary candidate site for intermolecular interactions. The structure of the
      conserved RBD of ALY provides insight into the nature of interactions involving
      this multifunctional protein.

PMID- 12809491
TI  - Noncompetitive antagonist binding sites in the torpedo nicotinic acetylcholine
      receptor ion channel. Structure-activity relationship studies using adamantane
      derivatives.
AB  - We used a series of adamantane derivatives to probe the structure of the
      phencyclidine locus in either the resting or desensitized state of the nicotinic
      acetylcholine receptor (AChR). Competitive radioligand binding and photolabeling
      experiments using well-characterized noncompetitive antagonists such as the
      phencyclidine analogue [piperidyl-3,4-(3)H(N)]-N-[1-(2-thienyl)cyclohexyl]-3,4
      piperidine ([(3)H]TCP), [(3)H]ethidium, [(3)H]tetracaine, [(14)C]amobarbital, and
      3-(trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine ([(125)I]TID) were
      performed. Thermodynamic and structure-function relationship analyses yielded the
      following results. (1) There is a good structure-function relationship for
      adamantane amino derivatives inhibiting [(3)H]TCP or [(3)H]tetracaine binding to
      the resting AChR. (2) Since the same derivatives inhibit neither
      [(14)C]amobarbital binding nor [(125)I]TID photoincorporation, we conclude that
      these positively charged molecules preferably bind to the TCP locus, perhaps
      interacting with alphaGlu(262) residues at position M2-20. (3) The opposite is
      true for the neutral molecule adamantane, which prefers the TID (or barbiturate)
      locus instead of the TCP site. (4) The TID site is smaller and more hydrophobic
      (it accommodates neutral molecules with a maximal volume of 333 +/- 45 A(3)) than
      the TCP locus, which has room for positively charged molecules with volumes as
      large as 461 A(3) (e.g., crystal violet). This supports the concept that the
      resting ion channel is tapering from the extracellular mouth to the middle
      portion. (5) Finally, although both the hydrophobic environment and the size of
      the TCP site are practically the same in both states, there is a more obvious
      cutoff in the desensitized state than in the resting state, suggesting that the
      desensitization process constrains the TCP locus. A plausible location of neutral
      and charged adamantane derivatives is shown in a model of the resting ion
      channel.

PMID- 12809492
TI  - Solution conformation of the antibody-bound tyrosine phosphorylation site of the
      nicotinic acetylcholine receptor beta-subunit in its phosphorylated and
      nonphosphorylated states.
AB  - Phosphorylation of the acetylcholine receptor (AChR) seems to be responsible for
      triggering several effects including its desensitization and aggregation at the
      postsynaptic membrane and probably initiates a signal transduction pathway at the
      postsynaptic membrane. To study the structural and functional role of the
      tyrosine phosphorylation site of the AChR beta-subunit and contribute to the in
      depth understanding of the structural basis of the ion channel function, we
      synthesized four peptides containing the phosphorylated and nonphosphorylated
      sequences (380-391) of the human and Torpedo AChR beta-subunits and studied their
      interaction with a monoclonal antibody (mAb 148) that is known to bind to this
      region and that is capable of blocking ion channel function. All four peptides
      were efficient inhibitors of mAb 148 binding to AChR, although the
      nonphosphorylated human peptide was considerably less effective than the three
      others. We then investigated the conformation acquired by all four peptides in
      their antibody-bound state, which possibly illustrates the local conformation of
      the corresponding sites on the intact AChR molecule. The phosphorylated human and
      Torpedo peptides adopted a distorted 3(10) helix conformation. The
      nonphosphorylated Torpedo peptide, which is also an efficient inhibitor, was also
      folded. In contrast, the nonphosphorylated human peptide (a less efficient
      inhibitor) presented an extended structure. It is concluded that the
      phosphorylation of the AChR at its beta-subunit Tyr site leads to a significant
      change in its conformation, which may affect several functions of the AChR.

PMID- 12809494
TI  - HU protein employs similar mechanisms of minor-groove recognition in binding to
      different B-DNA sites: demonstration by Raman spectroscopy.
AB  - The sequence isomers d(CGCAAATTTGCG) and d(TCAAGGCCTTGA) form self-complementary
      duplexes that present distinct targets for binding of the homodimeric
      architectural protein HU of Bacillus stearothermophilus (HUBst). Raman
      spectroscopy shows that although each duplex structure is of the B-DNA type,
      there are subtle conformational dissimilarities between them, involving torsion
      angles of the phosphodiester backbone and the arrangements of stacked bases. Each
      DNA duplex forms a stable stoichiometric (1:1) complex with HUBst, in which the
      structure of the HUBst dimer is largely conserved. However, the Raman signature
      of each DNA duplex is perturbed significantly and similarly with HUBst binding,
      as reflected in marker bands assigned to localized vibrations of the
      phosphodiester moieties and base residues. The spectral perturbations identify a
      reorganization of the DNA backbone and partial unstacking of bases with HUBst
      binding, which is consistent with non-sequence-specific minor-groove recognition.
      Prominent among the HUBst-induced perturbations of B-DNA are a conversion of
      approximately one-third of the alpha/beta/gamma torsions from the canonical g(
      )/t/g(+) conformation to an alternative conformation, an equivalent conversion of
      deoxyadenosyl moieties from the C2'-endo/anti to the C3'-endo/anti conformation,
      and appreciable unstacking of purines. The results imply that each solution
      complex is characterized by structural perturbations extending throughout the 12
      bp sequence. Comparison with previously studied protein/DNA complexes suggests
      that binding of HUBst bends DNA by approximately 70 degrees.

PMID- 12809493
TI  - Hurpin is a selective inhibitor of lysosomal cathepsin L and protects
      keratinocytes from ultraviolet-induced apoptosis.
AB  - Hurpin (headpin/PI13/serpinB13) is an intracellular, differentially spliced
      member of the serpin superfamily that has been linked to differentiation and
      apoptosis of human keratinocytes. It is transiently downregulated by UV light and
      overexpressed in psoriatic skin lesions. Although it has all of the features of
      an inhibitory serpin, a productive interaction between hurpin and a proteinase
      has not yet been reported. Here we demonstrate that hurpin is a potent and
      selective inhibitor of the archetypal lysosomal cysteine proteinase cathepsin L
      (catL). Recombinant hurpin inhibits human catL with a stoichiometry of inhibition
      (SI) of 1.7 and a rate constant k(assoc) of (4.6 +/- 0.14) x 10(5) M(-1) s(-1).
      It inefficiently inhibits catV and does not inhibit papain, catB, or catK. To
      investigate the inhibitory mechanism, we determined the P1-P1' bond in the
      reactive center loop cleaved by catL ((356)Thr-(357)Ser) and expressed variants
      in which the proximal hinge, P1 residue, or differentially spliced CD loop was
      mutated. The results of assays using these proteins suggest that inhibition of
      catL by hurpin occurs via the conventional serpin inhibitory mechanism and that
      the CD loop plays no role in the process. Finally, it was found that the majority
      of hurpin is cytosolic and that its overexpression in human keratinocytes confers
      resistance to UV-induced apoptosis. Given that lysosomal disruption, release of
      catL, and catL-mediated caspase activation are known to occur in response to
      cellular stress, we propose that a physiological role of hurpin is to protect
      epithelial cells from ectopic catL.

PMID- 12809495
TI  - Subunit III of cytochrome c oxidase of Rhodobacter sphaeroides is required to
      maintain rapid proton uptake through the D pathway at physiologic pH.
AB  - The catalytic core of cytochrome c oxidase is composed of three subunits where
      subunits I and II contain all of the redox-active metal centers and subunit III
      is a seven transmembrane helix protein that binds to subunit I. The N-terminal
      region of subunit III is adjacent to D132 of subunit I, the initial proton
      acceptor of the D pathway that transfers protons from the protein surface to the
      buried active site approximately 30 A distant. The absence of subunit III only
      slightly alters the initial steady-state activity of the oxidase at pH 6.5, but
      activity declines sharply with increasing pH, yielding an apparent pK(a) of 7.2
      for steady-state O(2) reduction. When subunit III is present, cytochrome oxidase
      is more active at higher pH, and the apparent pK(a) of steady-state O(2)
      reduction is 8.5. Single-turnover experiments show that proton uptake through the
      D pathway at pH 8 slows from >10000 s(-1) in the presence of subunit III to 350
      s(-1) in its absence. At low pH (5.5) the D pathway of the oxidase lacking
      subunit III regains its capacity for rapid proton uptake. Analysis of the F --> O
      transition indicates that the apparent pK(a) of the D pathway in the absence of
      subunit III is 6.8, similar to that of steady-state O(2) reduction (7.2). The
      pK(a) of D132 itself may decline in the absence of subunit III since its
      carboxylate group will be more exposed to solvent water. Alternatively, part of a
      proton antenna for the D pathway may be lost upon removal of subunit III. It is
      proposed that one role of subunit III in the normal oxidase is to maintain rapid
      proton uptake through the D pathway at physiologic pH.

PMID- 12809496
TI  - A role for subunit III in proton uptake into the D pathway and a possible proton
      exit pathway in Rhodobacter sphaeroides cytochrome c oxidase.
AB  - Protons are transferred from the inner surface of cytochrome c oxidase to the
      active site by the D and K pathways, as well as from the D pathway to the outer
      surface by a largely undefined proton exit route. Alteration of the initial
      proton acceptor of the D pathway, D132, to alanine has previously been shown to
      greatly inhibit oxidase turnover and slow proton uptake into the D pathway. Here
      it is shown that the removal of subunit III restores a substantial rate of O(2)
      reduction to D132A. Presumably an alternative proton acceptor for the D pathway
      becomes active in the absence of subunit III and D132. Thus, in the absence of
      subunit III cytochrome oxidase shows greater flexibility in terms of proton entry
      into the D pathway. In the presence of DeltaPsi and DeltapH, turnover of the wild
      type oxidase or D132A is slower in the absence of subunit III. Comparison of the
      turnover rates of subunit III-depleted wild-type oxidase to those of the zinc
      inhibited wild-type oxidase containing subunit III, both reconstituted into
      vesicles, leads to the hypothesis that the absence of subunit III inhibits the
      ability of the normal proton exit pathway to take up protons from the outside in
      the presence of DeltaPsi and DeltapH. Thus, subunit III appears to affect the
      transfer of protons from both the inner and outer surfaces of cytochrome oxidase,
      perhaps accounting for the long-observed lower efficiency of proton pumping by
      the subunit III-depleted oxidase.

PMID- 12809497
TI  - Stereoselectivity of each of the three steps of the heme oxygenase reaction:
      hemin to meso-hydroxyhemin, meso-hydroxyhemin to verdoheme, and verdoheme to
      biliverdin.
AB  - Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin
      IXalpha with concomitant liberation of CO and iron by three sequential
      monooxygenase reactions. The alpha-regioselectivity of heme oxygenase has been
      thought to result from the regioselective oxygenation of the heme alpha-meso
      position at the first step, which leads to the reaction pathway via meso
      hydroxyheme IXalpha and verdoheme IXalpha intermediates. However, recent reports
      concerning heme oxygenase forming biliverdin isomers other than biliverdin
      IXalpha raise a question whether heme oxygenase can degrade meso-hydroxyhemin and
      isomers other than the alpha-isomers. In this paper, we investigated the
      stereoselectivity of each of the two reaction steps from meso-hydroxyhemin to
      verdoheme and verdoheme to biliverdin by using a truncated form of rat heme
      oxygenase-1 and the chemically synthesized four isomers of meso-hydroxyhemin and
      verdoheme. Heme oxygenase-1 converted all four isomers of meso-hydroxyhemin to
      the corresponding isomers of verdoheme. In contrast, only verdoheme IXalpha was
      converted to the corresponding biliverdin IXalpha. We conclude that the third
      step, but not the second, is stereoselective for the alpha-isomer substrate. The
      present findings on regioselectivities of the second and the third steps have
      been discussed on the basis of the oxygen activation mechanisms of these steps.

PMID- 12809498
TI  - Recombinant water-soluble chlorophyll protein from Brassica oleracea var. Botrys
      binds various chlorophyll derivatives.
AB  - A gene coding for water-soluble chlorophyll-binding protein (WSCP) from Brassica
      oleracea var. Botrys has been used to express the protein, extended by a
      hexahistidyl tag, in Escherichia coli. The protein has been refolded in vitro to
      study its pigment binding behavior. Recombinant WSCP was found to bind two
      chlorophylls (Chls) per tetrameric protein complex but no carotenoids in
      accordance with previous observations with the native protein [Satoh, H.,
      Nakayama, K., Okada, M. (1998) J. Biol. Chem. 273, 30568-30575]. WSCP binds Chl
      a, Chl b, bacteriochlorophyll a, and the Zn derivative of Chl a but not
      pheophytin a, indicating that the central metal ion in Chl is essential for
      binding. WSCP also binds chlorophyllides a and b and even the more distant Chl
      precursor Mg-protoporphyrin IX; however, these pigments fail to induce
      oligomerization of the protein. We conclude that the phytol group in bound Chl
      plays a role in the formation of tetrameric WSCP complexes. If WSCP in fact binds
      Chl or its derivative(s) in vivo, the lack of carotenoids in pigmented WSCP
      raises the question of how photooxidation, mediated by triplet-excited Chl and
      singlet oxygen, is prohibited. We show by spin-trap electron-paramagnetic
      resonance that the light-induced singlet-oxygen formation of WSCP-bound Chl is
      lower by a factor of about 4 than that of unbound Chl. This as-yet-unknown
      mechanism of WSCP to protect its bound Chl against photooxidation supports the
      notion that WSCP may function as a transient carrier of Chl or its derivatives.

PMID- 12809499
TI  - Nearest neighbor analysis of the SecYEG complex. 1. Identification of a SecY-SecG
      interface.
AB  - Integral membrane components SecY, SecE, and SecG of protein translocase form a
      complex in the Escherichia coli plasma membrane. To characterize subunit
      interactions of the SecYEG complex, a series of SecY variants having a single
      cysteine in its cytoplasmic (C1-C6) or periplasmic (P1-P5) domain were subjected
      to site-specific cross-linking experiments using bifunctional agents with thiol
      amine reactivity. Experiments using inverted membrane vesicles revealed specific
      cross-linkings between a cysteine residue placed in the C2 or C3 domain of SecY
      and the cytosolic lysine (Lys26) near the first transmembrane segment of SecG.
      These SecY Cys residues also formed a disulfide bond with an engineered cytosolic
      cysteine at position 28 of SecG. Thus, the C2-C3 region of SecY is in the
      proximity of the N-terminal half of the SecG cytoplasmic loop. Experiments using
      spheroplasts revealed the physical proximity of P2 (SecY) and the C-terminal
      periplasmic region of SecG. In addition, mutations in secG were isolated as
      suppressors against a cold-sensitive mutation (secY104) affecting the TM4-C3
      boundary of SecY. These results collectively suggest that a C2-TM3-P2-TM4-C3
      region of SecY serves as an interface with SecG.

PMID- 12809500
TI  - Nearest neighbor analysis of the SecYEG complex. 2. Identification of a SecY-SecE
      cytosolic interface.
AB  - Although the importance of interactions involving both the cytosolic and
      transmembrane regions of SecY and SecE has been documented, no information has
      been available for the physical contact sites of these translocase subunits in
      their cytosolic domains. We now carried out site-specific cross-linking
      experiments to identify SecY and SecE regions that are physically close.
      Cysteines introduced into SecY residue 244 in the fourth cytosolic domain (C4) as
      well as into residues 354-356 and 362 in the C5 domain could be cross-linked with
      natural or engineered residues at positions 79 and 81 in the central part of the
      cytosolic loop of SecE. These cross-linkages were abolished by the Gly240
      mutation in the SecY C4 region as well as by prlG alterations in SecE
      transmembrane segment 3, known to compromise SecY-SecE interaction. We suggest
      that the cytosolic and intramembrane interactions bring these two subunits
      together, forming a functionally crucial SecYE interface involving the SecY C5
      region and the conserved cytosolic segment of SecE.

PMID- 12809501
TI  - The Na+/H+ exchanger cytoplasmic tail: structure, function, and interactions with
      tescalcin.
AB  - We characterized the regulatory cytoplasmic tail of the Na(+)/H(+) exchanger
      using a histidine-tagged protein containing the C-terminal 182 amino acids
      (His182). Both tescalcin and calmodulin, two Na(+)/H(+) exchanger binding
      proteins, bound to the His182 protein. Cascade blue was used to label the His182
      protein. Calcium caused an increase in fluorescence, suggesting exposure of the
      label on the protein to a more hydrophilic environment. Decreasing external pH
      caused a transient increase in cascade blue fluorescence, followed by a decrease
      in fluorescence of the cascade blue labeled Na(+)/H(+) exchanger C-terminus.
      Tescalcin caused a decrease in fluorescence by labeled His182 protein, and
      calcium reversed this effect. Expression of tescalcin in vivo inhibited activity
      of the Na(+)/H(+) exchanger when there was an intact C-terminus of the protein.
      We examined the CD spectra of His182 in the presence and absence of tescalcin.
      The C-terminal amino acids demonstrated a very small amount of alpha-helical
      structure and much more beta-sheet and beta-turn. This was not greatly affected
      by the presence of tescalcin, but calcium caused an increase in the amount of
      beta-structure and a decrease in the unstructured proportion of the protein.
      Sedimentation equilibrium analysis demonstrated that the C-terminal 182 amino
      acids exist predominantly as a monomer. The results suggest that the C-terminus
      of the Na(+)/H(+) exchanger exists primarily as a monomeric protein that binds
      regulatory tescalcin and can change conformation depending on pH and calcium.
      Conformation changes in this region of the protein may be responsible for
      altering the pH sensitivity of the intact Na(+)/H(+) exchanger.

PMID- 12809502
TI  - Peripheral binding mode and penetration depth of cobra cardiotoxin on
      phospholipid membranes as studied by a combined FTIR and computer simulation
      approach.
AB  - Cobra cardiotoxin, a cytotoxic beta-sheet basic polypeptide, is known to cause
      membrane leakage in many cells including human erythrocytes. Herein, we
      demonstrate that the major cobra cardiotoxin from Naja atra, CTX A3, can cause
      leakage of vesicle contents in phosphatidylglycerol (PG) and phosphatidylserine
      containing, but not in pure phosphatidylcholine (PC), membrane bilayers. By the
      combined polarized attenuated total reflection infrared spectroscopy and computer
      simulation studies, CTX A3 is shown to peripherally bind to both zwitterionic and
      anionic monolayers in a similar edgewise manner with a tilted angle of
      approximately 48 +/- 20 degrees between the beta-sheet plane of the CTX molecule
      and the normal of the membrane surface. The average surface area expansion
      induced by CTX A3 binding to the PG monolayer, however, is two times larger than
      that of the PC monolayer as determined by the Langmuir minitrough method.
      Interaction energy considerations of CTX A3 on neutral and negatively charged
      membrane surfaces suggests that the electrostatic interaction between anionic
      lipid and cationic CTXs plays a role in modulating the penetration depth of CTX
      molecules on the initial peripheral binding mode and reveals a pathway leading to
      the formation of an inserted mode in negatively charged membrane bilayers.

PMID- 12809503
TI  - Human DNA polymerase lambda diverged in evolution from DNA polymerase beta toward
      specific Mn(++) dependence: a kinetic and thermodynamic study.
AB  - The recently discovered human DNA polymerase lambda (DNA pol lambda) has been
      implicated in translesion DNA synthesis across abasic sites. One remarkable
      feature of this enzyme is its preference for Mn(2+) over Mg(2+) as the activating
      metal ion, but the molecular basis for this preference is not known. Here, we
      present a kinetic and thermodynamic analysis of the DNA polymerase reaction
      catalyzed by full length human DNA pol lambda, showing that Mn(2+) favors
      specifically the catalytic step of nucleotide incorporation. Besides acting as a
      poor coactivator for catalysis, Mg(2+) appeared to bind also to an allosteric
      site, resulting in the inhibition of the synthetic activity of DNA pol lambda and
      in an increased sensitivity to end product (pyrophosphate) inhibition. Comparison
      with the closely related enzyme human DNA pol beta, as well as with other DNA
      synthesising enzymes (mammalian DNA pol alpha and DNA pol delta, Escherichia coli
      DNA pol I, and HIV-1 reverse transcriptase) indicated that these features are
      unique to DNA pol lambda. A deletion mutant of DNA pol lambda, which contained
      the highly conserved catalytic core only representing the C-terminal half of the
      protein, showed biochemical properties comparable to the full length enzyme but
      clearly different from the close homologue DNA pol beta, highlighting the
      existence of important differences between DNA pol lambda and DNA pol beta,
      despite a high degree of sequence similarity.

PMID- 12809504
TI  - Novel phosphorylation target in the serum response factor MADS box regulates
      alpha-actin transcription.
AB  - Serum response factor (SRF) is a phosphoprotein that regulates skeletal and
      cardiac alpha-actin gene transcription. Myotonic dystrophy protein kinase (DMPK),
      a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity
      of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in
      nonmyogenic cells. DMPK phosphorylated SRF in vitro in the alphaI coil of the DNA
      binding domain in the MADS box, a highly conserved region required for DNA
      binding, dimerization, and co-activator interaction in COS and CV1 cells.
      Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target
      in vitro as well as in vivo of both DMPK and protein kinase C-alpha. Substitution
      of threonine 159 with the nonphosphorylatable residue alanine markedly diminished
      activation of the cardiac alpha-actin promoter in the presence of kinase, while
      its substitution with aspartic acid, to introduce a negative charge and mimic
      phosphorylation, restored activation completely. Phosphorylation of the MADS box
      may constitute a novel mechanism for regulation of SRF-dependent actin gene
      transcription.

PMID- 12809505
TI  - Association of an aminoacyl-tRNA synthetase with a putative metabolic protein in
      archaea.
AB  - Aminoacyl-tRNA synthetases are essential enzymes that catalyze attachment of
      amino acids to tRNAs for decoding of genetic information. In higher eukaryotes,
      several synthetases associate with non-synthetase proteins to form a high
      molecular mass complex that may improve the efficiency of protein synthesis. This
      multi-synthetase complex is not found in bacteria. Here we describe the isolation
      of a non-synthetase protein from the archaeon Methanocaldococcus jannaschii that
      was copurified with prolyl-tRNA synthetase (ProRS). This protein, Mj1338, also
      interacts with several other tRNA synthetases and has an affinity for general
      tRNA, suggesting the possibility of forming a multi-synthetase complex. However,
      unlike the non-synthetase proteins in the eukaryotic complex, the protein Mj1338
      is predicted to be a metabolic protein, related to members of the family of H(2)
      forming N(5),N(10)-methylene tetrahydromethanopterin (5,10-CH(2)-H(4)MP)
      dehydrogenases that are involved in the one-carbon metabolism of the archaeon.
      The association of Mj1338 with ProRS, and with other components of the protein
      synthesis machinery, thus suggests the possibility of a closer link between
      metabolism and decoding in archaea than in eukarya or bacteria.

PMID- 12809506
TI  - The first direct characterization of a high-valent iron intermediate in the
      reaction of an alpha-ketoglutarate-dependent dioxygenase: a high-spin FeIV
      complex in taurine/alpha-ketoglutarate dioxygenase (TauD) from Escherichia coli.
AB  - The Fe(II)- and alpha-ketoglutarate(alphaKG)-dependent dioxygenases have roles in
      synthesis of collagen and sensing of oxygen in mammals, in acquisition of
      nutrients and synthesis of antibiotics in microbes, and in repair of alkylated
      DNA in both. A consensus mechanism for these enzymes, involving (i) addition of
      O(2) to a five-coordinate, (His)(2)(Asp)-facially coordinated Fe(II) center to
      which alphaKG is also bound via its C-1 carboxylate and ketone oxygen; (ii)
      attack of the uncoordinated oxygen of the bound O(2) on the ketone carbonyl of
      alphaKG to form a bicyclic Fe(IV)-peroxyhemiketal complex; (iii) decarboxylation
      of this complex concomitantly with formation of an oxo-ferryl (Fe(IV)=O(2)(-))
      intermediate; and (iv) hydroxylation of the substrate by the Fe(IV)=O(2)(-)
      complex via a substrate radical intermediate, has repeatedly been proposed, but
      none of the postulated intermediates occurring after addition of O(2) has ever
      been detected. In this work, an oxidized Fe intermediate in the reaction of one
      of these enzymes, taurine/alpha-ketoglutarate dioxygenase (TauD) from Escherichia
      coli, has been directly demonstrated by rapid kinetic and spectroscopic methods.
      Characterization of the intermediate and its one-electron-reduced form (obtained
      by low-temperature gamma-radiolysis of the trapped intermediate) by Mossbauer and
      electron paramagnetic resonance spectroscopies establishes that it is a high
      spin, formally Fe(IV) complex. Its Mossbauer isomer shift is, however,
      significantly greater than those of other known Fe(IV) complexes, suggesting that
      the iron ligands in the TauD intermediate confer significant Fe(III) character to
      the high-valent site by strong electron donation. The properties of the complex
      and previous results on related alphaKG-dependent dioxygenases and other non-heme
      Fe(II)-dependent, O(2)-activating enzymes suggest that the TauD intermediate is
      most probably either the Fe(IV)-peroxyhemiketal complex or the taurine
      hydroxylating Fe(IV)=O(2)(-) species. The detection of this intermediate sets the
      stage for a more detailed dissection of the TauD reaction mechanism than has
      previously been reported for any other member of this important enzyme family.

PMID- 12809507
TI  - Coordinated production and utilization of FADH2 by NAD(P)H-flavin oxidoreductase
      and 4-hydroxyphenylacetate 3-monooxygenase.
AB  - 4-Hydroxyphenylacetate (4HPA) 3-monooxygenase (HpaB) is a reduced flavin adenine
      dinucleotide (FADH(2)) utilizing monooxygenase. Its cosubstrate, FADH(2), is
      supplied by HpaC, an NAD(P)H-flavin oxidoreductase. Because HpaB is the first
      enzyme for 4HPA metabolism, FADH(2) production and utilization become a major
      metabolic event when Escherichia coli W grows on 4HPA. An important question is
      how FADH(2) is produced and used, as FADH(2) is unstable in the presence of free
      O(2). One solution is metabolic channeling by forming a transitory HpaB-HpaC
      complex. However, our in vivo and in vitro data failed to support the
      interaction. Further investigation pointed to an alternative scheme for HpaB to
      sequester FADH(2). The intracellular HpaB concentration was about 122 microM in
      4HPA-growing cells, much higher than the total intracellular FAD concentration,
      and HpaB had a high affinity for FADH(2) (K(d) of 70 nM), suggesting that most
      FADH(2) is bound to HpaB in vivo. The HpaB-bound FADH(2) was either used to
      rapidly oxidize 4HPA or slowly oxidized by O(2) to FAD and H(2)O(2) in the
      absence of 4HPA. Thus, HpaB's high intracellular concentration, its high affinity
      for FADH(2), its property of protecting bound FADH(2) in the absence of 4HPA, and
      its ability to rapidly use FADH(2) to oxidize 4HPA when 4HPA is available can
      coordinate FADH(2) production and utilization by HpaB and HpaC in vivo. This type
      of coordination, in responding to demand, for production and utilization of
      labile metabolites has not been reported to date.

PMID- 12809508
TI  - Conversion of cyclodextrin glycosyltransferase into a starch hydrolase by
      directed evolution: the role of alanine 230 in acceptor subsite +1.
AB  - Cyclodextrin glycosyltransferase (CGTase) preferably catalyzes transglycosylation
      reactions, whereas many other alpha-amylase family enzymes are hydrolases.
      Despite the availability of three-dimensional structures of several
      transglycosylases and hydrolases of this family, the factors that determine the
      hydrolysis and transglycosylation specificity are far from understood. To
      identify the amino acid residues that are critical for the transglycosylation
      reaction specificity, we carried out error-prone PCR mutagenesis and screened for
      Bacillus circulans strain 251 CGTase mutants with increased hydrolytic activity.
      After three rounds of mutagenesis the hydrolytic activity had increased 90-fold,
      reaching the highest hydrolytic activity ever reported for a CGTase. The single
      mutation with the largest effect (A230V) occurred in a residue not studied
      before. The structure of this A230V mutant suggests that the larger valine side
      chain hinders substrate binding at acceptor subsite +1, although not to the
      extent that catalysis is impossible. The much higher hydrolytic than
      transglycosylation activity of this mutant indicates that the use of sugar
      acceptors is hindered especially. This observation is in favor of a proposed
      induced-fit mechanism, in which sugar acceptor binding at acceptor subsite +1
      activates the enzyme in transglycosylation [Uitdehaag et al. (2000) Biochemistry
      39, 7772-7780]. As the A230V mutation introduces steric hindrance at subsite +1,
      this mutation is expected to negatively affect the use of sugar acceptors. Thus,
      the characteristics of mutant A230V strongly support the existence of the
      proposed induced-fit mechanism in which sugar acceptor binding activates CGTase
      in a transglycosylation reaction.

PMID- 12809509
TI  - The role of human and mouse hepatic scavenger receptor class B type I (SR-BI) in
      the selective uptake of low-density lipoprotein-cholesteryl esters.
AB  - Low-density lipoprotein (LDL)-cholesteryl ester (CE) selective uptake has been
      demonstrated in nonhepatic cells overexpressing the scavenger receptor class B
      type I (SR-BI). The role of hepatic SR-BI toward LDL, the main carrier of plasma
      CE in humans, remains unclear. The aim of this study was to determine if SR-BI,
      expressed at its normal level, is implicated in LDL-CE selective uptake in human
      HepG2 hepatoma cells and mouse hepatic cells, to quantify its contribution and to
      determine if LDL-CE selective uptake is likely to occur in the presence of human
      HDL. First, antibody blocking experiments were conducted on normal HepG2 cells.
      SR-BI/BII antiserum inhibited (125)I-LDL and (125)I-HDL(3) binding (10 microg of
      protein/mL) by 45% (p < 0.05) and CE selective uptake by more than 85% (p < 0.01)
      for both ligands. Second, HepG2 cells were stably transfected with a eukaryotic
      vector expressing a 400-bp human SR-BI antisense cDNA fragment. Clone 17 (C17)
      has a 70% (p < 0.01) reduction in SR-BI expression. In this clone, (3)H-CE-LDL
      and (3)H-CE-HDL(3) association (10 microg of protein/mL) was 54 +/- 6% and 45 +/-
      7% of control values, respectively, while (125)I-LDL and (125)I-HDL(3) protein
      association was 71 +/- 3% and 58 +/- 5% of controls, resulting in 46% and 55% (p
      < 0.01) decreases in LDL- and HDL(3)-CE selective uptake. Normalizing CE
      selective uptake for SR-BI expression reveals that SR-BI is responsible for 68%
      and 74% of LDL- and HDL(3)-CE selective uptake, respectively. Thus, both
      approaches show that, in HepG2 cells, SR-BI is responsible for 68-85% of CE
      selective uptake. Other pathways for selective uptake in HepG2 cells do not
      require CD36, as shown by anti-CD36 antibody blocking experiments, or class A
      scavenger receptors, as shown by the lack of competition by poly(inosinic acid).
      However, CD36 is a functional oxidized LDL receptor on HepG2 cells, as shown by
      antibody blocking experiments. Similar results for CE selective uptake were
      obtained with primary cultures of hepatic cells from normal (+/+), heterozygous (
      /+), and homozygous (-/-) SR-BI knockout mice. Flow cytometry experiments show
      that SR-BI accounts for 75% of DiI-LDL uptake, the LDL receptor for 14%, and
      other pathways for 11%. CE selective uptake from LDL and HDL(3) is likely to
      occur in the liver, since unlabeled HDL (total and apoE-free HDL(3)) and LDL,
      when added in physiological proportions, only partially competed for LDL- and
      HDL(3)-CE selective uptake. In this setting, human hepatic SR-BI may be a crucial
      molecule in the turnover of both LDL- and HDL(3)-cholesterol.

PMID- 12809510
TI  - Temperature-induced conformational switch in intestinal fatty acid binding
      protein (IFABP) revealing an alternative mode for ligand binding.
AB  - IFABP is a small beta-barrel protein with a short helix-turn-helix motif near the
      N-terminus that is thought to participate in the regulation of the uptake and
      delivery of fatty acids. In a previous work, we detected by near UV circular
      dichroism a reversible conformational transition of this protein occurring
      between 35 and 50 degrees C in the absence of fatty acids. The addition of the
      natural ligand oleic acid prevents this phenomenon. In both cases, the overall
      structure of the beta-barrel is maintained. This thermal transition is also
      detected by the fluorescent probe bis-anilino naphthalene sulfonic acid (bisANS)
      but not by its monomer ANS. In the present work, we studied in detail the
      interaction of each compound with IFABP as a function of temperature and in the
      absence or in the presence of oleic acid. A contrasting behavior was observed for
      these probes: (i) IFABP is able to bind two molecules of bisANS but only one
      molecule of ANS and (ii) oleic acid can fully displace ANS but only partially
      bisANS. Three independent lines of evidence, namely, fluorescence spectroscopy,
      circular dichroism, and limited proteolysis, indicate that there is an
      equilibrium among different conformations of IFABP, which differ in the extent of
      flexibility of the helical domain. This equilibrium can be shifted by raising
      temperature. bisANS is able to probe a population of IFABP in an altered state,
      which is more susceptible to cleavage by clostripain as compared to the apo-form,
      whereas the conformation of IFABP bound to oleic acid is characteristically more
      ordered. These results highlight the idea of an enhanced flexibility exhibited by
      IFABP that bears importance on its transport function, supporting the role of a
      dynamic entry portal region for the fatty acid ligand.

PMID- 12809511
TI  - Reconstitution reveals additional roles for N- and C-terminal domains of g(alpha)
      in muscarinic receptor coupling.
AB  - The molecular basis for selectivity of M1 and M2 muscarinic receptor coupling to
      heterotrimeric G proteins has been studied using receptors expressed in Sf9 cell
      membranes and reconstituted with purified chimeric G(alpha) subunits containing
      different regions of Gi1alpha and Gq(alpha). The abilities of G protein
      heterotrimers containing chimeric alpha subunits to stabilize the high-affinity
      state of the receptors for agonist and to undergo receptor stimulated guanine
      nucleotide exchange was compared with G protein heterotrimers containing either
      native Gi1alpha or Gq(alpha). The data confirm the importance of the proper
      context of the C-terminus of Galpha by demonstrating that the C-terminus of
      Gi1alpha, when placed in the context of Gq(alpha), prevents coupling to
      muscarinic M1 receptors, while the C-terminus of Gq(alpha), when placed in the
      context of Gi1alpha, prevents coupling to muscarinic M2 receptors. However, C
      terminal amino acids of Gq(alpha) placed in the context of Gi1alpha were not
      sufficient to allow M1 receptor coupling, nor were C-terminal amino acids of
      Gi1alpha placed in the context of Gq(alpha) sufficient for M2 receptor coupling.
      The unique six amino acid N-terminal extension of Gq(alpha) when added to the N
      terminus of Gi1alpha neither prevented M2 receptor coupling nor permitted M1
      receptor coupling. A Gi1alpha-based chimera containing both N- and C-terminal
      regions of Gq(alpha) gained the ability to productively couple M1 receptors
      suggesting that the proper context of both N- and C-termini is required for
      muscarinic receptor coupling.

PMID- 12809512
TI  - Different biological effects of unmodified prolactin and a molecular mimic of
      phosphorylated prolactin involve different signaling pathways.
AB  - Previous work has shown that naturally phosphorylated prolactin antagonizes the
      growth-promoting activities of unmodified prolactin (U-PRL) and that this effect
      is duplicated by a molecular mimic, S179D PRL. At the same time, the S179D PRL is
      a superagonist with regard to expression of some PRL-regulated genes. We have
      asked whether the different activities of U-PRL and S179D PRL are the result of
      differential signaling. HC11 cells (a normal mouse mammary cell line) were grown
      to confluence, primed with hydrocortisone, and then exposed to the PRLs. A 15 min
      incubation of PRL-naive cells led to substantial tyrosine phosphorylation of Jak
      2 and Stat 5a by U-PRL and an essentially equivalent Jak 2 activation by S179D
      PRL. The latter, however, was accompanied by reduced tyrosine phosphorylation of
      Stat 5a. EMSA analysis using a Stat 5 binding site showed both PRLs to cause
      equivalent binding of nuclear proteins and that most of what bound was complexed
      through Stat 5a. Phosphoamino acid analysis of Stat 5 showed S179D PRL to double
      the amount of serine phosphorylation versus that seen with U-PRL. Analysis of the
      MAP kinase pathway showed U-PRL capable of activation of ERKs 1 and 2 but that
      signaling via ERKs 1 and 2 was greater with S179D PRL. A 7-day incubation in
      either PRL increased beta-casein mRNA levels, but S179D PRL caused a 2-fold
      increase over that seen with U-PRL. The increase, over that seen with U-PRL, was
      blocked by the MAP kinase inhibitor, PD98059. After 7 days of treatment with
      S179D PRL, expression of the short PRL receptor was doubled, and signaling showed
      a greater dependence on the MAP kinase pathway (2.9-fold increase in ERK 1 and 2
      activation). We conclude that although both PRLs use both pathways to some
      extent, U-PRL signals primarily through Jak 2-Stat 5 whereas S179D PRL signals
      primarily through the MAP kinase pathway especially after prolonged exposure.
      This is the first demonstration of differential involvement of signaling pathways
      by different forms of PRL.

PMID- 12809513
TI  - Identification of the putative MAP kinase docking site in the thyroid hormone
      receptor-beta1 DNA-binding domain: functional consequences of mutations at the
      docking site.
AB  - In CV-1 cells transfected with wild-type (wt) nuclear thyroid hormone receptor
      TRbeta1 (TR), L-thyroxine (T(4)) causes activation and nuclear translocation of
      mitogen-activated protein kinase (MAPK, ERK1/2), co-immunoprecipitation of MAPK
      and TR, and MAPK-dependent serine phosphorylation of TR. In the present studies,
      we have identified (1) the likely site of TR serine phosphorylation in the TR DNA
      binding domain (DBD) by T(4)-activated MAPK, (2) the site of MAPK docking on TR
      induced by T(4), and (3) functional consequences of TR docking site and serine
      phosphorylation site mutations on co-repressor and co-activator binding and on
      transcriptional activation by wt and mutant receptors in T(4)-treated cells.
      Plasmids containing TR(wt), serine 142-substituted TR (TR(S142A) or TR(S142E)),
      TR(K128A), TR(R132A), or TR(R133A) were transfected into CV-1 cells, and the
      cells were treated with 10(-7) M T(4) for 30 min. Activated MAPK was present in
      nuclear fractions of all T(4)-treated cells and co-immunoprecipitated prominently
      with TR(wt), TR(S142A), and TR(S142E). TR(K128A) complexing with activated MAPK
      was minimally detectable, but no association of MAPK with TR(R132A) or TR(R133A)
      was seen in cells treated with T(4). Serine phosphorylation of TR(wt), but not of
      any mutants, occurred with T(4). In in vitro phosphorylation studies,
      constitutively activated MAPK phosphorylated only TR(wt). We concluded that
      serine 142 of the TR DBD is the likely site of phosphorylation by T(4)-activated
      MAPK and that the docking site on TR for activated MAPK includes residues 128-133
      (KGFFRR), a basic amino acid-enriched motif novel for MAPK substrates. TR
      mutations in the proposed MAPK docking domain and at residue 142 modulated T(4)
      conditioned shedding of co-repressor and recruitment of co-activator proteins by
      the receptor, and they altered transcriptional activity of TR in a thyroid
      hormone response element-luciferase reporter assay.

PMID- 12809514
TI  - Catalytic site-directed gamma-secretase complex inhibitors do not discriminate
      pharmacologically between Notch S3 and beta-APP cleavages.
AB  - The generation of gamma-secretase inhibitors which block the release of beta
      amyloid peptide (Abeta) has long been an attractive therapeutic avenue for
      treatment or prevention of Alzheimer's disease (AD). Such inhibitors would reduce
      levels of Abeta available for aggregation into toxic assemblies that lead to the
      plaque pathology found in affected brain tissue. Cumulative evidence suggests
      that the S3 cleavage of Notch is also dependent on presenilins (PS) and is
      carried out by the multimeric PS-containing gamma-secretase complex. It is
      therefore possible that Notch function could be affected by gamma-secretase
      inhibitors. To assess the relationship between the cleavage of these substrates
      in the same system, Western blot cleavage assays have been established using a
      human cell line stably expressing both the beta-amyloid precursor protein (beta
      APP) and the truncated Notch1 receptor fragment NotchDeltaE. Thus, a direct
      correlation may be made, following inhibitor treatment, of the decrease in the
      levels of the cleavage products, Abeta peptide and the Notch intracellular domain
      (NICD), as well as the increase in stabilized levels of both substrates. This
      analysis has been performed with a range of selected gamma-secretase inhibitors
      from six distinct structural classes. Changes in all four species usually occur
      in concert and with remarkably good agreement. A significant cleavage window is
      not clearly apparent in any case. Thus, these Notch and beta-APP cleavages cannot
      be dissected apart easily since they show the same pharmacological profile of
      inhibition. Whether this translates into proportionally reduced Notch signaling
      in vivo, however, remains to be seen.

PMID- 12809515
TI  - High-precision, high-throughput stability determinations facilitated by robotics
      and a semiautomated titrating fluorometer.
AB  - The use of statistical modeling to test hypotheses concerning the determinants of
      protein structure requires stability data (e.g., the free energy of denaturation
      in H(2)O, DeltaG(HOH)) from hundreds of protein mutants. Fluorescence-monitored
      chemical denaturation provides a convenient method for high-precision, high
      throughput DeltaG(HOH) determination. For eglin c we find that a throughput of
      about 20 min per protein can be attained in a two-channel semiautomated titrating
      fluorometer. We find also that the use of robotics for protein purification and
      preparation of the solutions for chemical denaturation gives highly precise
      DeltaG(HOH) values in which the standard deviation of values from multiple
      preparations (+/-0.051 kcal/mol) differs very little from multiple measurements
      from a single preparation (+/-0.040 kcal/mol). Since the variance introduced into
      model fitting by DeltaG(HOH) increases as the square of measurement error, there
      is a premium on precision. In fact, the fraction of stability behavior explicable
      by otherwise perfect models goes from 98% to only 50% over the error range
      commonly reported for chemical denaturation measurements (0.1-0.6 kcal/mol). We
      have found that the precision of chemical denaturation DeltaG(HOH) measurements
      depends most heavily on the precision of the instrument used, followed by protein
      purity and the capacity to precisely prepare the solutions used for titrations.

PMID- 12809516
TI  - Testing hypotheses about determinants of protein structure with high-precision,
      high-throughput stability measurements and statistical modeling.
AB  - Statistical modeling provides the mathematics to use data from large numbers of
      mutant proteins to generate information about hypotheses concerning protein
      structure not easily obtained from anecdotal studies on small numbers of mutants.
      Here we use the unfolding free energies of 303 unique eglin c mutant proteins
      obtained from high-precision, high-throughput chemical denaturation measurements
      to assess models concerning helix stability. A model with helix propensity as the
      sole determinant of stability accounts for 83% of the mutant-to-mutant variation
      in stability for 99% of the mutant proteins (three outliers). When position
      effects and side chain-side chain interactions are added to the model, the
      fraction of variation explained increases to 92%. The propensity parameters in
      this model are identical to helix propensity values derived from other
      approaches. Measurement error accounts for another 1% of the mutant-to-mutant
      variation in stability. While the data support terms for several of the expected
      stabilizing/destabilizing effects, it does not support terms for several others,
      including i, i + 3 effects in the center of the helix and helix-dipole effects.
      In addition, the model does better with terms for several
      stabilizing/destabilizing effects for which we cannot identify the physical
      basis. The precision of our unfolding stability measurements (+/-0.087 kcal/mol)
      allows us to conclude that the 7% of variation in stabilities of the mutant
      proteins not accounted for by the model or by measurement variation is both real
      and large with respect to the nonpropensity terms in the model. The analysis also
      shows that the common practice of using C(m)m(av) instead of C(m)m(mut) to
      calculate DeltaG(HOH,N-D) values for each mutant protein results in a loss of
      information. We see no correlation between the residuals derived from the full
      model and m(mut) - m(wt), and hence it is unlikely our m(mut) values reflect
      mutant-to-mutant differences in the denatured state.

PMID- 12809517
TI  - Rupture of the hydrogen bond linking two Omega-loops induces the molten globule
      state at neutral pH in cytochrome c.
AB  - His26Tyr and His33Tyr mutants were obtained from the Cys102Thr variant of yeast
      iso-1-cytochrome c. Spectroscopic studies show that a mutation at position 26 at
      pH 7.0 enhances flexibility of the peptide, alters the heme pocket region and the
      axial coordination to heme-iron, and reduces protein stability. The His26Tyr
      mutant shows properties typical of the molten globule. Further, formation of an
      axially misligated minor low spin species occurs with partial displacement of
      Met80, the axial ligand of the heme-iron in the native protein. The pK(a)
      determined for the alkaline transition of this mutant is 7.48 (+/- 0.05),
      approximately 0.5 lower than that of the wild-type protein. Hence, the alkaline
      conformer is populated at pH 7.0, and the sixth ligand of the misligated species
      is proposed to be a lysine. Furthermore, a reduction in catalytic activity
      indicates that the functional properties are altered. The results suggest that
      the structural and functional changes observed in the His26Tyr mutant are because
      the mutation frees the two Omega-loops that, in the native protein, are linked by
      the hydrogen bond between His26 and Glu44. Hence, one may infer that the His26
      Glu44 hydrogen bond is essential for the rigidity and stability of the native
      protein. In its absence, the heightened flexibility of the peptide fold results
      in conversion of the macromolecule to a molten globule state, even at neutral pH.
      Ligand exchange at the sixth coordination position of the heme-iron(III) observed
      as the minor species (i.e., the alkaline conformer) is therefore induced by a
      long-range effect. This result is of interest since mutations reported to date,
      which stabilize the alkaline conformer, all occur in the loop including Met80. By
      contrast, only very minor spectroscopic (and, thus, structural) changes are
      observed for the His33Tyr mutant. This suggests that His33 does not form
      intramolecular bonds considered important for the protein structure and
      stability, and is consistent with the high variability of residues at position 33
      in cytochromes c.

PMID- 12809518
TI  - Trehalose favors a cutinase compact intermediate off-folding pathway.
AB  - The folding of cutinase, an enzyme displaying lipolytic activity, has been
      studied in the presence of trehalose. Equilibrium unfolding data show that
      trehalose increases the free energy change between folded and unfolded states.
      Unfolding kinetics reveal the presence of an intermediate which is ca. 60% folded
      in terms of solvent exposure. Trehalose stabilizes this intermediate relative to
      the folded state. In contrast, the intermediate revealed by folding kinetics is
      more compact than the transition state, as shown by the positive slope observed
      at low denaturant concentration in the chevron plot, as well as the decrease in
      the observable rate constant for folding with the increase in trehalose
      concentration. This intermediate displays more than 50% of area buried from the
      solvent (relative to the native state) compared to around 40% for the transition
      state for folding and therefore appears to be off the folding pathway. Trehalose
      stabilizes and guanidine hydrochloride destabilizes this compact intermediate.
      Both unfolding and folding kinetics show that compact conformational states are
      stabilized by trehalose, in agreement with current models on the effect of
      compatible solutes. This effect occurs even for compact states that decelerate
      the folding as in the case of the intermediate revealed by folding kinetics.

PMID- 12809519
TI  - Troponin I binds polycystin-L and inhibits its calcium-induced channel
      activation.
AB  - Polycystin-L (PCL) is an isoform of polycystin-2, the product of the second gene
      associated with autosomal dominant polycystic kidney disease, and functions as a
      Ca(2+)-regulated nonselective cation channel. We recently demonstrated that
      polycystin-2 interacts with troponin I, an important regulatory component of the
      actin microfilament complex in striated muscle cells and an angiogenesis
      inhibitor. In this study, using the two-microelectrode voltage-clamp technique
      and Xenopus oocyte expression system, we showed that the calcium-induced PCL
      channel activation is substantially inhibited by the skeletal and cardiac
      troponin I (60% and 31% reduction, respectively). Reciprocal co
      immunoprecipitation experiments demonstrated that PCL physically associates with
      the skeletal and cardiac troponin I isoforms in overexpressed Xenopus oocytes and
      mouse fibroblast NIH 3T3 cells. Furthermore, both native PCL and cardiac troponin
      I were present in human heart tissues where they indeed associate with each
      other. GST pull-down and microtiter binding assays showed that the C-terminus of
      PCL interacts with the troponin I proteins. The yeast two-hybrid assay further
      verified this interaction and defined the corresponding interacting domains of
      the PCL C-terminus and troponin I. Taken together, this study suggests that
      troponin I acts as a regulatory subunit of the PCL channel complex and provides
      the first direct evidence that PCL is associated with the actin cytoskeleton
      through troponin I.

PMID- 12809520
TI  - Investigation of the role and mechanism of IF1 and STF1 proteins, twin inhibitory
      peptides which interact with the yeast mitochondrial ATP synthase.
AB  - Inhibition of the yeast F(0)F(1)-ATP synthase by the regulatory peptides IF1 and
      STF1 was studied using intact mitochondria and submitochondrial particles from
      wild-type cells or from mutants lacking one or both peptides. In intact
      mitochondria, endogenous IF1 only inhibited uncoupled ATP hydrolysis and
      endogenous STF1 had no effect. Addition of alamethicin to mitochondria readily
      made the mitochondrial membranes permeable to nucleotides, and bypassed the
      kinetic control exerted on ATP hydrolysis by the substrate carriers. In addition,
      alamethicin made the regulatory peptides able to cross mitochondrial membranes.
      At pH 7.3, F(0)F(1)-ATPase, initially inactivated by either endogenous IF1 or
      endogenous STF1, was completely reactivated hours or minutes after alamethicin
      addition, respectively. Previous application of a membrane potential favored the
      release of endogenous IF1 and STF1. These observations showed that IF1 and STF1
      can fully inhibit ATP hydrolysis at physiological concentrations and are
      sensitive to the same effectors. However, ATP synthase has a much lower affinity
      for STF1 than for IF1, as demonstrated by kinetic studies of ATPase inhibition in
      submitochondrial particles by externally added IF1 and STF1 at pHs ranging from
      5.5 to 8.0. Our data do not support previously proposed effects of STF1, like the
      stabilization of the IF1-F(0)F(1) complex or the replacement of IF1 on its
      binding site in the presence of the proton-motive force or at high pH, and raise
      the question of the conditions under which STF1 could regulate ATPase activity in
      vivo.

PMID- 12809521
TI  - Chemical biology of signal transduction.

PMID- 12809523
TI  - The raison d'etre of constitutively active protein kinases: the lesson of CK2.
AB  - Protein kinases generally are tightly controlled signaling molecules that are
      switched on only in response to specific stimuli. Exceptionally few protein
      kinases are constitutively active, the most striking example being provided by
      CK2 (formerly "casein kinase 2"). Owing to unique structural features, the
      catalytic activity of CK2 is constantly on, although its targeting can be deeply
      influenced by the association of its two catalytic subunits (alpha and/or alpha')
      with a dimeric non catalytic beta subunit. Constitutive activity of CK2 reflects
      its extraordinary pleiotropy documented by its growing list of >300 protein
      substrates and is consistent with emerging evidence that CK2 plays an essential
      role in the cell by counteracting premature and/or unscheduled apoptosis, thus
      ensuring cell survival under stress conditions.

PMID- 12809522
TI  - Applications of one-bead one-compound combinatorial libraries and chemical
      microarrays in signal transduction research.
AB  - The "one-bead-one-compound" (OBOC) combinatorial library method synthesizes
      millions of random compounds such that each bead displays only one compound. Bead
      libraries are screened, and positive beads are isolated for structure analysis.
      Peptide substrates and inhibitors of protein kinases, and peptide ligands for
      cell surface receptors have been identified using this method. A novel encoding
      strategy for OBOC libraries has been developed to identify peptidomimetic and
      small-molecule ligands that specifically interact with cellular proteins. These
      ligands will be tested for their effects on cell signaling and used to construct
      chemical microarrays for further characterization of ligand-protein interactions.

PMID- 12809524
TI  - Chemical and mechanistic approaches to the study of protein tyrosine
      phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are signaling enzymes that control a diverse
      array of cellular processes. Site-directed mutagenesis, combined with detailed
      kinetic and mechanistic studies of Yersinia PTP, have contributed greatly to the
      understanding of the chemical mechanism for PTP catalysis, the nature of the
      enzymatic transition state, and the means by which the transition state is
      stabilized. Significant progress has been made in developing specific small
      molecule inhibitors as tools to dissect the functional roles of PTP both in
      normal physiology and pathological conditions. Despite the conserved structural
      and catalytic properties, recent results show that there are sufficient
      differences in the PTPs so that potent and selective bidentate inhibitors that
      simultaneously bind both the active site and a unique adjacent site can be
      obtained.

PMID- 12809526
TI  - Chemical probes of signal-transducing proteins.
AB  - Protein kinases are key participants in signal transduction pathways. A direct
      assessment of the relationship between the activity of any given protein kinase
      and the corresponding cellular phenotype has proven challenging. This is due to
      the large number of protein kinases encoded by the human genome coupled with
      intracellular temporal and spatial constraints that appear to further regulate
      the ultimate response of a cell to a stimulus. Our work has focused on the
      development of chemical probes to address the complexities associated with
      protein kinase-mediated cell signaling. These include the acquisition of highly
      selective substrates and inhibitors for specific members of the protein kinase
      family, the design and synthesis of light-activated signaling proteins and their
      corresponding inhibitors, and the preparation of fluorescent reporters of
      intracellular protein kinase action.

PMID- 12809525
TI  - Determinants of substrate recognition in nonreceptor tyrosine kinases.
AB  - Cytoplasmic tyrosine kinases do not occur as isolated catalytic domains. Instead,
      each kinase family possesses a characteristic array of additional domains that
      are appended to the catalytic domain. The combination and the arrangement of
      these modular domains are important in kinase regulation and function. This
      Account describes how the noncatalytic regions of Src family tyrosine kinases are
      involved in enzyme regulation, substrate selection, and multisite
      phosphorylation.

PMID- 12809527
TI  - Specificity is complex and time consuming: mutual exclusivity in tyrosine kinase
      mediated signaling.
AB  - Most fundamental cellular processes are transduced through tyrosine kinase (TK)
      mediated pathways. For transduction without corruption, the protein-protein
      interactions involved have to be mutually exclusive. Many of these proteins bind
      via homologous domains whose binding characteristics suggest that their innate
      specificity is not sufficiently high to account for the integrity of signal
      transduction. Stimulation of TK-mediated signals is often accompanied by
      recruitment of a precise, multimolecular protein complex that is itself capable
      of imposing specificity. Furthermore, this complex provides protection against
      phosphatase activity, controlling the longevity of the active signaling complex,
      and thus influencing outcomes in subsequent downstream events.

PMID- 12809528
TI  - Roscovitine and other purines as kinase inhibitors. From starfish oocytes to
      clinical trials.
AB  - This article reviews the steps that have led us from very fundamental research on
      the cell division cycle, investigated with the starfish oocyte model, to the
      identification of drugs now being evaluated against cancer in the clinic. Among
      protein kinases activated during entry in M phase, the cyclin-dependent kinase
      CDK1/cyclin B was initially identified as a universal M-phase promoting factor.
      It was then used as a screening target to identify pharmacological inhibitors.
      The first inhibitors to be discovered were 6-dimethylaminopurine and
      isopentenyladenine, from which more potent and selective inhibitors were
      optimized (olomoucine, roscovitine, and purvalanols). All were cocrystallized
      with CDK2 and found to localize in the ATP-binding pocket of the kinase. Their
      selectivity and cellular effects have been thoroughly investigated. Following
      encouraging results obtained in preclinical tests and favorable pharmacological
      properties, one of these purines, roscovitine (CYC202), is now entering phase II
      clinical trials against cancers and phase I clinical tests against
      glomerulonephritis. CDK inhibitors are also being evaluated, at the preclinical
      level, for therapeutic use against neurodegenerative diseases, cardiovascular
      disorders, viral infections, and parasitic protozoa. This initially unexpected
      scope of potential applications and the large number and chemical diversity of
      pharmacological inhibitors of CDKs now available constitute a very encouraging
      stimulus to pursue the search for optimization and characterization of protein
      kinase inhibitors, from which we expect numerous therapeutic applications.

PMID- 12809529
TI  - Phosphotyrosyl mimetics in the development of signal transduction inhibitors.
AB  - Phosphotyrosyl (pTyr) residues play important roles in cellular signal
      transduction by facilitating recognition and binding necessary for critical
      protein-protein interactions, and for this reason pTyr motifs represent
      attractive starting points in the development of signaling antagonists. Although
      the pTyr phosphoryl moiety is central in these phenomena, its incorporation into
      signaling inhibitors is contraindicated due to enzymatic lability and limited
      bioavailability associated with phosphate esters. To address these limitations,
      an entire field of study has arisen devoted to the design and utilization of pTyr
      mimetics. This Account provides a perspective on the roles of pTyr residues in
      signal transduction and approaches to pTyr mimetic development.

PMID- 12809530
TI  - Synthetic diacylglycerols (DAG) and DAG-lactones as activators of protein kinase
      C (PK-C).
AB  - The central role of protein kinase C (PK-C) in cellular signal transduction has
      established it as an important therapeutic target for cancer and other diseases.
      We have developed a series of 4,4-disubstituted-gamma-butyrolactones, which
      contain a constrained glycerol backbone (DAG-lactones) and behave as potent and
      selective activating ligands of PK-C with affinities that approach those of the
      structurally complex natural product agonists, such as the phorbol esters. This
      Account traces the design and construction of these molecules. Initially, we
      examined the consequences of reducing the entropic penalty associated with the
      transformation of a DAG into a DAG-lactone. Then, using molecular modeling to
      extend insights arising from the newly solved crystal structure of a C1 domain
      complexed with phorbol ester, we incorporated amino acid-specific branched
      hydrophobic chains to provide a new generation of DAG-lactones that have the
      capacity to bind to PK-C with low nanomolar affinity. Depending on the specific
      pattern of hydrophobic substitution, some DAG-lactones are able to induce
      selective translocation of individual PK-C isozymes to different cellular
      compartments, and since the specific nature of these hydrophobic interactions
      influences biological outcome, some of these compounds exhibit cell-specific
      antitumor activity. The ability to direct specific PK-C isozyme translocation
      with sets of structurally simple, yet highly potent molecules provides a powerful
      tool for engineering a plethora of molecules with novel biological functions.

PMID- 12809531
TI  - Chemical approaches to reversible protein phosphorylation.
AB  - Protein phosphorylation catalyzed by protein kinases plays a critical role in
      cellular signaling. Here we review several chemical approaches to understanding
      protein kinases and the consequences of protein phosphorylation. We discuss the
      design of bisubstrate analogue inhibitors based on a dissociative transition
      state, the development of reagents for cross-linking protein kinases with their
      substrates, the chemical rescue of mutant protein tyrosine kinases, and the
      application of expressed protein ligation to understanding protein
      phosphorylation.

PMID- 12809532
TI  - The characterization of protein post-translational modifications by mass
      spectrometry.
AB  - Most biological processes are regulated by post-translational modifications of
      proteins, and conditions that disrupt the regulation of such events can lead to
      disease. In the past decade, the identification and characterization of covalent
      modifications have been driven by advances in mass spectrometry. Here, we discuss
      current mass spectrometric and proteomic approaches for the identification of
      proteins and their covalent modifications, and we highlight high-throughput
      strategies for comprehensive analysis of cell proteomes.

PMID- 12809533
TI  - Protein kinase inhibitors as a therapeutic modality.
AB  - Most of the signal transduction pathways are mediated by protein kinases
      regulating every aspect of cell function. Mutations which deregulate their
      expression or their function or both result in cancers. Therefore, protein kinase
      inhibitors has become the focus of development of new therapies for cancer.
      Almost all 120 protein tyrosine kinases are involved in signaling, whereas only a
      handful of Ser/Thr kinases are involved. Thus, most of the effort is directed
      toward the development of tyrosine phosphorylation inhibitors. The success of
      Gleevec in the treatment of chronic myeloid leukemia and of Iressa for lung
      cancer validates the approach.

PMID- 12809534
TI  - Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and
      implications for assessment of exposure risk of chronic beryllium disease.
AB  - The continued occurrence of chronic beryllium disease (CBD) suggests the current
      occupational exposure limit of 2 microg beryllium per cubic meter of air does not
      adequately protect workers. This study examined the morphology and measured the
      particle surface area of aerodynamically size-separated powders and process
      sampled particles of beryllium metal, beryllium oxide, and copper-beryllium
      alloy. The beryllium metal powder consisted of compact particles, whereas the
      beryllium oxide powder and particles were clusters of smaller primary particles.
      Specific surface area (SSA) results for all samples (N=30) varied by a factor of
      37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the
      process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the
      </=0.4 microm size fraction of the metal powder). Large relative differences in
      SSA were observed as a function of particle size for the powder of beryllium
      metal, from 4.0 +/- 0.01 m(2)/g (for the particle size fraction >6 microm) to
      20.8 +/- 0.44 m(2)/g (for the particle size fraction </=0.4 microm). In contrast,
      little relative difference in SSA (<25%) was observed as a function of particle
      size for the beryllium oxide powder and particles collected from the screening
      operation. The SSA of beryllium metal powder decreases with increasing particle
      size, as expected for compact particles, and the SSA of the beryllium oxide
      powders and particles remains constant as a function of particle size, which
      might be expected for clustered particles. These associations illustrate how
      process-related factors can influence the morphology and SSA of beryllium
      materials. To avoid errors in predicting bioavailability of beryllium and the
      associated risks for CBD, the mechanisms of particle formation should be
      understood and the SSA of beryllium particles should be measured directly.

PMID- 12809535
TI  - The impact of a change to inhalable occupational exposure limits: strontium
      chromate exposure in the U.S. Air Force.
AB  - The American Conference of Governmental Industrial Hygienists has announced its
      intention to replace all total particulate threshold limit values (TLVs) with
      size-selective TLVs. Because the U.S. Air Force has adopted the TLVs as its
      occupational exposure limits, the impact of this change is of interest,
      specifically for hexavalent chromium. This article reviews historical strontium
      chromate sampling data in the Air Force and the impact of its reinterpretation in
      comparison to an inhalable TLV. Based on the measured conversion factor between
      the 37-mm cassette and the IOM inhalable sampler, inhalable strontium chromate
      exposures will continue to exceed the TLV during all aircraft priming and most
      sanding procedures. In addition, inhalable exposures are expected to exceed 1000
      times the TLV, greater than the highest currently assigned protection factor for
      airline respirators, during 25% of priming procedures. Without a change in the
      value of the current TLV time-weighted average of 0.5 microg/m(3), the Air Force
      will need to reduce strontium chromate levels, either by incorporating work
      practices that decrease worker productivity or considering a change to
      nonchromated primers.

PMID- 12809536
TI  - Laboratory and field testing of particle size-selective sampling methods for
      mineral dusts.
AB  - The performances of eight sampling devices were tested with mineral dusts in the
      laboratory and in a talc production plant. The IOM sampler was chosen as the
      reference method for inhalable dust, and the IOM samplers provided with the
      porous plastic foam media were used as the reference methods for both the
      thoracic and respirable aerosols. The other size-selective instruments tested
      included the Respicon virtual impactor, the optical GRIMM aerosol monitor, and a
      two-stage cascade impactor with cut points of 10 and 4 microm. The 37-mm
      cassettes were also included both as open- and closed-face versions. The study
      confirmed the usability of the IOM samplers for mineral dust, not only in its
      original version for the inhalable fraction but also its modified versions for
      the thoracic and respirable fractions. A high correlation with the two-stage
      impactor results is an indication of good reproducibility. The results increased
      the evidence that the 37-mm cassette is a poor indicator of inhalable aerosol.
      The concentrations obtained with both cassette methods were not only
      systematically too low but also showed large collection efficiency variability.
      Therefore, the results cannot be corrected by using correction factors. The
      concentrations of inhalable aerosol measured with the Respicon were generally
      low, but its performances for the thoracic and respirable fractions were closer
      to those for the reference samplers. The results also indicate that the GRIMM
      monitor is well-suited for such mineral dust determinations when very good
      accuracy is not required, but the immediate availability of the result is more
      important.

PMID- 12809537
TI  - Silica dust exposures during selected construction activities.
AB  - This study characterized exposure for dust-producing construction tasks. Eight
      common construction tasks were evaluated for quartz and respirable dust exposure
      by collecting 113 personal task period samples for cleanup; demolition with
      handheld tools; concrete cutting; concrete mixing; tuck-point grinding; surface
      grinding; sacking and patching concrete; and concrete floor sanding using both
      time-integrating filter samples and direct-reading respirable dust monitors. The
      geometric mean quartz concentration was 0.10 mg/m(3) (geometric standard
      deviation [GSD]=4.88) for all run time samples, with 71% exceeding the threshold
      limit value. Activities with the highest exposures were surface grinding, tuck
      point grinding, and concrete demolition (GM[GSD] of 0.63[4.12], 0.22[1.94], and
      0.10[2.60], respectively). Factors recorded each minute were task, tool, work
      area, respiratory protection and controls used, estimated cross draft, and
      whether anyone nearby was making dust. Factors important to exposure included
      tool used, work area configuration, controls employed, cross draft, and in some
      cases nearby dust. More protective respirators were employed as quartz
      concentration increased, although respiratory protection was found to be
      inadequate for 42% of exposures. Controls were employed for only 12% of samples.
      Exposures were reduced with three controls: box fan for surface grinding and
      floor sanding, and vacuum/shroud for surface grinding, with reductions of 57, 50,
      and 71%, respectively. Exposures were higher for sweeping compound, box fan for
      cleanup, ducted fan dilution, and wetted substrate. Construction masons and
      laborers are frequently overexposed to silica. The usual protection method,
      respirators, was not always adequate, and engineering control use was infrequent
      and often ineffective.

PMID- 12809538
TI  - Statistical comparison of diesel particulate matter measurement methods.
AB  - Four methods are used to quantify diesel particulate matter (DPM) in the mine
      environment: respirable combustible dust sampling (RCD), size selective sampling
      with gravimetric analysis (SSG), respirable dust sampling with elemental carbon
      (EC) analysis, and respirable dust sampling with total carbon (TC) analysis. The
      authors assembled data from three underground mine studies to statistically
      compare these methods. The sampling protocol used in each study was similar. For
      all the four methods, samples were collected in triplicate at three locations
      upwind and downwind of the diesel scoop and on the scoop. The methods were
      compared with respect to their precision, selectivity, sensitivity, and LOD, as
      well as their limitations in measuring DPM concentrations. This constitutes a
      meta-analysis of the available data and provides information over a broader range
      of mining conditions and DPM concentrations than any of the individual studies.
      The weighing imprecision for the SSG method is almost twice that for the RCD
      technique. The imprecision of the EC and TC methods are a function of the mass
      loading, and EC has a lower imprecision than TC. The EC method was used as the
      reference "gold standard" against which the other methods were evaluated. The
      RCD, SSG, and TC methods exhibited substantial levels of interference, leading to
      much higher minimum concentrations that can be measured by these methods. Of the
      three, the SSG method has the highest level of interference, primarily from
      nondiesel material that is collected in the <0.8 microm size range.

PMID- 12809539
TI  - Occupational exposure to diesel exhaust in the Canadian federal jurisdiction.
AB  - To assess the impact of the proposed American Conference of Governmental
      Industrial Hygienists threshold limit value-time-weighted average to diesel
      particulate matter (DPM), 177 full-shift samples were taken in 23 workplaces
      under Canadian federal jurisdiction. National Institute for Occupational Safety
      and Health (NIOSH) Method 5040 (Elemental Carbon: Diesel Exhaust) was used to
      assess exposure. Quality control tests were conducted prior to field sampling by
      taking air samples in the exhaust stream of two diesel engines mounted on a test
      bed and having them analyzed by two laboratories using the same thermal program.
      Field sampling results indicated that 77% of the elemental carbon (EC) levels
      were below the currently proposed limit of 20 microg/m(3), and 54% below 10
      microg/m(3). The geometric mean concentration of EC was 24.4 microg/m(3) in high
      activity and 4.0 microg/m(3) in low-activity work sites. Corresponding arithmetic
      mean concentrations were 41.4 and 8.4 microg/m(3), respectively. The ratio of EC
      to total carbon (TC) was close to 90% for all quality control samples. It was no
      higher than 50% for the field samples, and it varied significantly with EC
      concentration. Finally, results are presented from the analysis of 41 samples by
      a third laboratory using a thermal-optical method slightly different from NIOSH
      5040. Even if one were to opt for EC as a surrogate for DPM, unless analysis
      details (particularly the thermal program) are specified, significant differences
      in the results can be expected. This could lead to problems for regulatory
      agencies and for epidemiologic research.

PMID- 12809540
TI  - Construction work practices and conditions improved after 2-years' participation
      in the HomeSafe pilot program.
AB  - This study reevaluated changes in job-site safety audit scores for a cohort of
      residential construction workers that had protracted exposure to the HomeSafe
      pilot program for 2(1/2) years. The investigation was a repeated measure of a
      cohort study underway in the six-county metro area of Denver, Colo. The larger
      study was a longitudinal, quasi-experimental design with a cohort of residential
      construction workers within the HomeSafe strategic partnership between
      Occupational Safety and Health Administration Region VIII and the Home Builders
      Association of Metropolitan Denver (HBA). Audits were conducted on residential
      construction sites. Study subjects were construction workers employed by partner
      or control companies within the study. Repeated measures of 41 companies showed
      significant improvement (p=.01) in audit scores, increasing from 71.8 to 76.8
      after 2(1/2) years in the program. HomeSafe companies out-performed controls
      (p=.01) for both the retest group and previously unaudited HomeSafe companies.
      Prolonged exposure in the HomeSafe pilot program resulted in improved audit
      scores for companies within the program for at least 2 years.

PMID- 12809541
TI  - Heat stress evaluation and worker fatigue in a steel plant.
AB  - This study assessed fatigue in electric arc melting workers (ER) and continuous
      casting workers (CC) in a steel plant and evaluated their physiological response
      to different levels of heat stress. Fifty-five men participated in the study. The
      ER group (mean, standard deviation [SD]=41.6, 7.4 years) was significantly older
      than the CC group (34.9, 6.4 years). The wet bulb globe temperature (WBGT) index
      of the workplace was measured. Workers' subjective fatigue symptoms were
      investigated by a 30-item constructive questionnaire, and physiological
      conditions and response time were measured before and after work for 2
      consecutive days. WBGT ranged from 25.4 approximately 28.7 degrees C and 30.0
      approximately 33.2 degrees C for the CC and ER areas, respectively. After age
      adjustment the ER group had significantly higher prevalence rates in subjective
      symptoms and slower response time than the CC group. The response "thirsty" was
      the highest after work (75 and 60% for the 2 ER interview days, respectively). A
      high prevalence (over 40%) of "eyes feel strained," "perception of shoulders
      stiff," or "feel waist pain" also was observed. Average pre- and postwork ER
      group systolic pressures were 129.1+/-11.4 mmHg (mean+/-SD) and 126.1+/-12.1
      mmHg, 132.5+/-11.4 and 130.6+/-11.2 mmHg for the CC group. Continuous heat-strain
      monitoring data from one ER and one CC worker indicated that average working
      heart rate and body temperature were well below 150 beats/min and 38 degrees C.
      Faster response in critical flicker fusion was found after work than before work,
      but the differences were not statistically significant (p>.05). Response time for
      the falling bar grasp was faster at the beginning of work, declined with working
      time, and rebounded at the end of work. Workers exposed to a hot environment are
      inclined to subjective fatigue, and their fatigue symptoms increase with the heat
      exposure levels. However, low resting heart rate and systolic pressure are two
      characteristics for high heat exposure workers.

PMID- 12809542
TI  - Evaluation of a personal monitor employing an electrochemical sensor for
      assessing exposure to hydrogen peroxide in the workplace.
AB  - A commercially available direct-reading instrument designed for personal
      monitoring of vapor phase hydrogen peroxide (VHP) was evaluated in the laboratory
      and the workplace. Monitoring VHP has gained increasing importance in the
      pharmaceutical industry because sterilization using VHP has proven to be a good
      alternative to previously used sterilizing methods. The current Occupational
      Safety and Health Administration impinger method for VHP measurements, based on
      bubbling air through an acid solution with subsequent laboratory analysis, is not
      practical for monitoring personal exposures. By employing an electrochemical
      sensor, the instrument evaluated provides real-time exposure data with auxiliary
      functions such as displaying concentrations in parts per million, data logging,
      and alarms. A double-dilution technique using a syringe pump was used to generate
      dynamic test atmospheres ranging from 0.2 to 10 ppm in an exposure chamber. Time
      weighted average concentration data from the direct-reading instrument was
      compared with concentration data from the impingers. The overall accuracy was
      less than the +/-25%, National Institute for Occupational Safety and Health
      criterion. No significant differences in accuracy were observed at three humidity
      levels (i.e., 15, 50, and 80%). The instrument was similarly evaluated in a
      workplace under typical conditions. The results agreed within +/-0.2 ppm.
      Selected performance characteristics of the instrument also were investigated,
      including reproducibility, response and recovery times, calibration frequency,
      and suitability of the calibration adapter. Results of the investigation suggest
      that the instrument provides a means for simple and accurate monitoring of
      personal exposures to VHP in workplace environments.

PMID- 12809543
TI  - Using a spreadsheet to compute contaminant exposure concentrations given a
      variable emission rate.
AB  - Two key elements of mathematical exposure models are the contaminant's emission
      rate and pattern of dispersion in room air. Assuming that the mass emission rate
      is constant and room air is perfectly mixed affords relative mathematical
      simplicity. However, treating a highly variable emission rate as constant
      underestimates peak exposure intensity, which may be toxicologically important,
      and assuming a well-mixed condition underestimates exposure intensity near the
      source. In the past decade multizone models and turbulent diffusion models have
      been used to account for spatial variability in airborne concentrations, and
      variable emission rate functions have been described for different processes. Due
      to the greater complexity of these models, closed-form equations for
      concentration as a function of time may not be available. This article presents a
      numerical method that combines a variable contaminant emission rate function with
      the three dispersion constructs most commonly used by industrial hygienists-the
      well-mixed room, the near field/far field, and hemispherical turbulent eddy
      diffusion. The article describes how the numerical method is implemented by a
      computer spreadsheet program, and illustrates the method using a sinusoidal
      contaminant emission rate function.

PMID- 12809544
TI  - A prospective field study of the relationship of potential occupational risk
      factors with occupational injury/illness.
AB  - Twenty-one occupationally related risk factors were measured and prospectively
      evaluated for statistically significant relationships with occupational
      injury/illness in 442 manual material handlers, working for three different
      companies, at nine U.S. locations, and encompassing 15 different job
      descriptions. OSHA 200 logs were used to ascertain evidence of occupational
      injury/illness (dichotomous) within this population for 1 year after the testing
      and measurement were completed. The present study demonstrated evidence of a
      subset of critical variables significantly related to occupational injury/illness
      occurrence through the significantly related occupational risk factors presented
      in the univariate and multivariate models. Higher occurrences of injury/illness
      were significantly associated with nine risk factors in the univariate model,
      with odds ratios ranging from 1.11-2.27. The significantly (p<0.05) related risk
      factors in the univariate model were lifting frequency; weight lifted per day;
      weight lifted per hour; number of trunk flexions per hour; number of trunk twists
      per hour; number of trunk motions per hour; number of knee flexions per hour;
      number of shoulder flexions per hour; and static shoulder flexion. In the
      multivariate analysis two risk factors were associated with occupational
      injury/illness. The significantly (p<0.05) related risk factors in the
      multivariate model were lifting frequency (p=0.0010, odds ratio [OR]=4.47, 95%
      confidence interval [CI]=[2.38-8.40], and average weight of lift (p=0.0001,
      OR=1.71, 95% CI=[1.29-2.25]).

PMID- 12809545
TI  - Effects of garage employment and tobacco smoking on breathing-zone concentrations
      of carbonyl compounds.
AB  - Exposure to carbonyl compounds may cause adverse health effects. The present
      study examined whether working in a garage and smoking can significantly affect
      personal "daily" exposure to a number of important carbonyl compounds. The study
      was carried out on 37 subjects including 22 garage workers (9 smokers and 13
      nonsmokers) and 15 nongarage workers or so-called controls (4 smokers and 11
      nonsmokers). Daily exposure was estimated using 48-hour integrated measurement of
      breathing-zone concentrations. The measurement involved the use of a passive
      carbonyl sampler and high performance liquid chromatography/fluorescence analysis
      technique. Each subject was measured for up to three measurement sessions. A wide
      range of breathing-zone concentrations (unit: microgram per cubic meter) was
      observed for each of the following carbonyls: formaldehyde (14.1-80.1);
      acetaldehyde (8.41-80.3); acetone (0.65-1096); acrolein (<0.14-3.71);
      propionaldehyde (1.08-14.6); crotonaldehyde (<0.13-2.80); benzaldehyde (1.79
      9.91); and hexaldehyde (0.122-22.4). Statistical significance of smoking effects
      and working in a garage effects were assessed using SAS mixed models. The results
      show that the garage workers had significantly higher levels of formaldehyde and
      acetaldehyde than the controls, and that the smokers had significantly higher
      levels of acetaldehyde, propionaldehyde, and hexaldehyde, than the nonsmokers
      (P<.10). Garage employment and smoking appeared to increase breathing-zone
      concentrations of crotonaldehyde. In general, within-subject variations were
      smaller than between-subject variations on 48-hour averaged breathing-zone
      concentrations of carbonyl compounds.

PMID- 12809546
TI  - Environmental agricultural tractor cab filter efficiency and field evaluation.
AB  - To evaluate filter efficiency and performance of environmental enclosures for
      tractors, 3- to 4-year-old tractor enclosure combinations (cabs retrofitted to
      tractors after manufacturing) were studied at a custom pesticide applicators
      facility. Optical particle counters were used to measure the aerosol number
      concentration inside and outside the cab. The ratio of these concentrations
      multiplied by 100 is termed percentage penetration, the amount of the aerosol
      that penetrates into the enclosure. For particles in the 0.3 to 0.4 microm range,
      penetration into the cab was reduced from 11 to 0.4% in the following sequential
      steps. First, manufacturing mistakes were corrected by fixing a bowed flange and
      inappropriate sealing of the sheet metal used to separate incoming air from air
      that had passed through the filter. This reduced aerosol penetration from 11 to
      4.8%. Replacing gasket material on the used filter reduced penetration from 4.8
      to 0.65%. This suggests that the filter gaskets are deforming and allowing
      leakage. Also, the filter media were evaluated for aerosol penetration as a
      function of particle size and were tested per the criteria stipulated in 42 CFR
      84 for negative pressure air-purifying particulate respirators. These results
      showed penetration through the filter media of less than 0.03%, indicating that
      filter media were not a major source of aerosol leakage into the cab. The results
      suggest that the manufacturer should implement a quality control program to
      ensure that minimal aerosol penetration criteria into the cabs are met and an
      acceptable maintenance program exists to ensure compliance. Furthermore, the
      degradation of filter gasket material over time needs to be minimized to ensure
      that the environmental cabs continue to provide acceptable performance.

PMID- 12809547
TI  - Applying mathematical modeling to create job rotation schedules for minimizing
      occupational noise exposure.
AB  - This research developed worker schedules by using administrative controls and a
      computer programming model to reduce the likelihood of worker hearing loss. By
      rotating the workers through different jobs during the day it was possible to
      reduce their exposure to hazardous noise levels. Computer simulations were made
      based on data collected in a real setting. Worker schedules currently used at the
      site are compared with proposed worker schedules from the computer simulations.
      For the worker assignment plans found by the computer model, the authors
      calculate a significant decrease in time-weighted average (TWA) sound level
      exposure. The maximum daily dose that any worker is exposed to is reduced by
      58.8%, and the maximum TWA value for the workers is reduced by 3.8 dB from the
      current schedule.

PMID- 12809548
TI  - Comparison of alternate methods of preparing wood sports floors for recoating.
AB  - Recreational wood sports surfaces receive periodic refinishing. Most school
      sports floors are recoated annually. The two primary methods of preparing wooden
      sports floors (creating a "bondable" surface for recoating), "dry abrasion" and
      "wet abrasion," were examined for employee dust exposure. Refinishing workers'
      personal total dust exposures were measured for a large collegiate basketball
      court, a community center gymnasium, and two racquetball courts as well as areas
      immediately adjoining the work areas. The refinishing workers breathing zone
      total dust concentrations ranged from 7.2 to 39.0 mg/m(3) and for adjacent areas
      were 1.1 to 5.3 mg/m(3) for the dry abrasion method. During wet abrasion there
      were no detectable particles (<0.5 mg/m(3)) in either the work areas or the
      immediately adjoining areas. The authors conclude the wet abrasion method can
      control dust levels adequately to prevent cross-contamination of adjacent areas
      while preventing worker exposures. Further studies in this area would be of
      interest, particularly determining the nature of the dust and whether it contains
      any wood component, because certain hardwood dusts have been listed as confirmed
      human carcinogens.

PMID- 12809549
TI  - Using an extractive Fourier transform infrared spectrometer for improving
      cleanroom air quality in a semiconductor manufacturing plant.
AB  - A mobile extractive Fourier transform infrared (FTIR) spectrometer was
      successfully used to locate, identify, and quantify the "odor" sources inside the
      cleanroom of a semiconductor manufacturing plant. It was found that ozone (O(3))
      gas with a peak concentration of 120 ppm was unexpectedly releasing from a
      headspace of a drain for transporting used ozonized water and that silicon
      tetrafluoride (SiF(4)) with a peak concentration of 3 ppm was off-gassed from
      silicon wafers after dry-etching processing. When the sources of the odors was
      pinpointed by the FTIR, engineering control measures were applied. For O(3)
      control, a water-sealed pipeline was added to prevent the O(3) gas (emitting from
      the ozonized water) from entering the mixing unit. A ventilation system also was
      applied to the mixing unit in case of O(3) release. For SiF(4) mitigation, before
      the wafer-out chamber was opened, N(2) gas with a flow rate of 150 L/min was used
      for 100 sec to purge the wafer-out chamber, and a vacuum system was
      simultaneously activated to pump away the purging N(2). The effectiveness of the
      control measures was assured by using the FTIR. In addition, the FTIR was used to
      monitor the potential hazardous gas emissions during preventative maintenance of
      the semiconductor manufacturing equipment.

PMID- 12809550
TI  - Expression of melanotransferrin isoforms in human serum: relevance to Alzheimer's
      disease.
AB  - Levels of soluble melanotransferrin in serum have been reported to be higher in
      patients with Alzheimer's disease than in control subjects. The present study
      investigated melanotransferrin in human body fluids in the light of these
      findings. To clarify the correlation between melanotransferrin and Alzheimer's
      disease, the melanotransferrin content was determined by non-reducing, denaturing
      SDS/PAGE and Western blotting. Under these conditions, serum melanotransferrin
      migrated at 79 and 82 kDa. Melanotransferrin antigenicity and the relative
      proportions of the two forms were very sensitive to factors that altered its
      conformation, including disulphide bridges, pH and bivalent cations. Serum
      melanotransferrin levels were not significantly different between control
      subjects and patients with Alzheimer's disease using whole serum, EDTA
      supplemented serum or serum immunoglobulin-depleted by Protein G-Sepharose and
      enriched by affinity precipitation with the lectin from Asparagus pea.
      Glycosylated forms of serum melanotransferrin bound to Asparagus lectin
      manifested similar patterns on two-dimensional gel electrophoresis in samples
      from controls and Alzheimer's disease subjects. Melanotransferrin was also
      present in saliva and at a high level in urine, but contents were similar in
      controls and patients with Alzheimer's disease. Together, these results
      demonstrate that serum melanotransferrin exists in various conformations
      depending on the binding of bivalent cations or following post-translational
      modification. These data also indicate that human serum melanotransferrin levels
      are unchanged in subjects with Alzheimer's disease.

PMID- 12809551
TI  - The metabolism of nitrosothiols in the Mycobacteria: identification and
      characterization of S-nitrosomycothiol reductase.
AB  - When grown in culture Mycobacterium smegmatis metabolized S-nitrosoglutathione to
      oxidized glutathione and nitrate, which suggested a possible involvement of an S
      nitrosothiol reductase and mycobacterial haemoglobin. The mycothiol-dependent
      formaldehyde dehydrogenase from M. smegmatis was purified by a combination of
      Ni2+-IMAC (immobilized metal ion affinity chromatography), hydrophobic
      interaction, anion-exchange and affinity chromatography. The enzyme had a subunit
      molecular mass of 38263 kDa. Steady-state kinetic studies indicated that the
      enzyme catalyses the NAD+-dependent conversion of S-hydroxymethylmycothiol into
      formic acid and mycothiol by a rapid-equilibrium ordered mechanism. The enzyme
      also catalysed an NADH-dependent decomposition of S-nitrosomycothiol (MSNO) by a
      sequential mechanism and with an equimolar stoichiometry of NADH:MSNO, which
      indicated that the enzyme reduces the nitroso group to the oxidation level of
      nitroxyl. Vmax for the MSNO reductase reaction indicated a turnover per subunit
      of approx. 116700 min(-1), which was 76-fold faster than the formaldehyde
      dehydrogenase activity. A gene, Rv2259, annotated as a class III alcohol
      dehydrogenase in the Mycobacterium tuberculosis genome was cloned and expressed
      in M. smegmatis as the C-terminally His6-tagged product. The purified recombinant
      enzyme from M. tuberculosis also catalysed both activities. M. smegmatis S
      nitrosomycothiol reductase converted MSNO into the N -hydroxysulphenamide, which
      readily rearranged to mycothiolsulphinamide. In the presence of MSNO reductase,
      M. tuberculosis HbN (haemoglobin N) was converted with low efficiency into metHbN
      [HbN(Fe3+)] and this conversion was dependent on turnover of MSNO reductase.
      These observations suggest a possible route in vivo for the dissimilation of S
      nitrosoglutathione.

PMID- 12809552
TI  - Synergistic effects of epoxy- and amine-silanes on microarray DNA immobilization
      and hybridization.
AB  - Most microarray slides are manufactured or coated with a layer of poly(L-lysine)
      or with silanes with different chemical functional groups, for the attachment of
      nucleic acids on to their surfaces. The efficiency with which nucleic acids bind
      to these surfaces is not high, because they can be washed away, especially in the
      case of spotting oligonucleotides. In view of this, we have developed a method to
      increase the binding capacity and efficiency of hybridization of DNA on to
      derivatized glass surfaces. This makes use of the synergistic effect of two
      binding interactions between the nucleic acids and the coating chemicals on the
      surface of the glass slides. The enhanced binding allows the nucleic acids to be
      bound tightly and to survive stringency washes. When immobilized, DNA exhibits a
      higher propensity for hybridization on the surface than on slides with only one
      binding chemical. By varying the silane concentrations, we have shown that
      maximal DNA oligonucleotide binding on glass surfaces occurs when the percentage
      composition of both of the surface-coating chemicals falls to 0.2%, which is
      different from that on binding PCR products. This new mixture-combination
      approach for nucleic-acid binding allows signals from immobilization and
      hybridization to have higher signal-to-noise ratios than for other silane-coated
      methods.

PMID- 12809553
TI  - Phosphorylation of BATF regulates DNA binding: a novel mechanism for AP-1
      (activator protein-1) regulation.
AB  - BATF is a member of the AP-1 (activator protein-1) family of bZIP (basic leucine
      zipper) transcription factors that form transcriptionally inhibitory, DNA binding
      heterodimers with Jun proteins. In the present study, we demonstrate that BATF is
      phosphorylated in vivo on multiple serine and threonine residues and at least one
      tyrosine residue. Reverse-polarity PAGE revealed that serine-43 and threonine-48
      within the DNA binding domain of BATF are phosphorylated. To model
      phosphorylation of the BATF DNA binding domain, serine-43 was replaced by an
      aspartate residue. BATF(S43D) retains the ability to dimerize with Jun proteins
      in vitro and in vivo, and the BATF(S43D):Jun heterodimer localizes properly to
      the nucleus of cells. Interestingly, BATF(S43D) functions like wild-type BATF to
      reduce AP-1-mediated gene transcription, despite the observed inability of the
      BATF(S43D):Jun heterodimer to bind DNA. These data demonstrate that
      phosphorylation of serine-43 converts BATF from a DNA binding into a non-DNA
      binding inhibitor of AP-1 activity. Given that 40% of mammalian bZIP
      transcription factors contain a residue analogous to serine-43 of BATF in their
      DNA binding domains, the phosphorylation event described here represents a
      mechanism that is potentially applicable to the regulation of many bZIP proteins.

PMID- 12809554
TI  - Association of human kinesin superfamily protein member 4 with BRCA2-associated
      factor 35.
AB  - A large portion of human kinesin superfamily protein member 4 (KIF4) is
      associated with the nuclear matrix during the interphase, while a small portion
      is found in the cytoplasm. During mitosis, it is associated with chromosomes
      throughout the entire process. In the present study, we identified a protein that
      interacts with KIF4 using a yeast two-hybrid system, co-immunoprecipitation and
      co-fractionation. This protein is BRCA2-associated factor 35 (BRAF35) containing
      a non-specific DNA binding high-mobility-group domain and a kinesin-like coiled
      coil domain. It appeared that the interaction between the two proteins occurs
      through their respective alpha-helical coiled-coil domains. The co-fractionation
      experiment revealed that KIF4 and BRAF35 were present in a complex of approx. 540
      kDa. The composition and biological significance of this complex should be
      studied further.

PMID- 12809555
TI  - Differential spatial and temporal phosphorylation of the visual receptor,
      rhodopsin, at two primary phosphorylation sites in mice exposed to light.
AB  - Phosphorylation of rhodopsin critically controls the visual transduction cascade
      by uncoupling it from the G-protein transducin. The kinase primarily responsible
      for this phosphorylation is rhodopsin kinase, a substrate-regulated kinase that
      phosphorylates light-activated rhodopsin. Protein kinase C has been implicated in
      controlling the phosphorylation of both light-activated and dark-adapted
      rhodopsin. Two of the major rhodopsin phosphorylation sites in vivo, Ser(334) and
      Ser(338), are effective protein kinase C phosphorylation sites in vitro, while
      the latter is preferentially phosphorylated by rhodopsin kinase in vitro. Using
      phosphospecific antibodies against each of these two sites, we show that both
      sites are under differential spatial and temporal regulation. Exposure of mice to
      light results in rapid phosphorylation of Ser(338) that is evenly distributed
      along the rod outer segment. Phosphorylation of Ser(334) is considerably slower,
      begins at the base of the rod outer segment, and spreads to the top of the
      photoreceptor over time. In addition, we show that phosphorylation of both sites
      is abolished in rhodopsin kinase(-/-) mice, revealing an absolute requirement for
      rhodopsin kinase to phosphorylate rhodopsin. This requirement may reflect the
      need for priming phosphorylations at rhodopsin kinase sites allowing for
      subsequent phosphorylation by protein kinase C at Ser(334). In this regard,
      treatment of mouse retinas with phorbol esters results in a 4-fold increase in
      phosphorylation on Ser(334), with no significant effect on the phosphorylation of
      Ser(338). Our results are consistent with light triggering rapid priming
      phosphorylations of rhodopsin by rhodopsin kinase, followed by a slower
      phosphorylation on Ser(334), which is regulated by protein kinase C.

PMID- 12809556
TI  - Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin
      and decreases calcipressin half-life.
AB  - Calcipressin 1 is an endogenous inhibitor of calcineurin, which is a
      serine/threonine phosphatase under the control of Ca(2+) and calmodulin.
      Calcipressin 1 is encoded by DSCR1, a gene on human chromosome 21 with seven
      exons, exons 1-4 are alternative first exons (isoforms 1-4). We show that
      calcipressin 1 isoform 1 has an N-terminal coding region longer than that
      previously described, and this generates a new polypeptide of 252 amino acids.
      This polypeptide is able to interact with calcineurin A and to inhibit NF-AT
      mediated transcriptional activation. We demonstrate for the first time that
      endogenous calcipressin 1 exists as a complex together with the calcineurin A and
      B heterodimer. Calcipressin 1 is a phosphoprotein that increases its capacity to
      inhibit calcineurin when phosphorylated at the FLISPP motif, and this
      phosphorylation also controls the half-life of calcipressin 1 by accelerating its
      degradation. Additionally, we have also detected further phosphorylation sites
      outside the FLISPP motif and these contribute to the complex phosphorylation
      pattern of calcipressin 1. Taking all these results into consideration we suggest
      that phosphorylation of calcipressin 1 is involved in the regulation of the
      phosphatase activity of calcineurin and can therefore act as a modulator of
      calcineurin-dependent cellular pathways.

PMID- 12809557
TI  - Cumulus cells steroidogenesis is influenced by the degree of oocyte maturation.
AB  - BACKGROUND: The possibility to predict the ability of a germ cell to properly
      sustain embryo development in vitro or in vivo as early as possible is
      undoubtedly the main problem of reproductive technologies. To date, only the
      achievement of nuclear maturation and cumulus expansion is feasible, as all the
      studies on cytoplasmic maturation are too invasive and have been complicated by
      the death of the cells analyzed. The authors studied the possibility to test the
      cytoplasmic quality of pig oocytes by evaluating their ability to produce
      steroidogenesis enabling factor(s). To this aim, oocytes matured under different
      culture conditions that allowed to obtain gradable level of cytoplasmic
      maturation, were used to produce conditioned media (OCM). The secretion of the
      factor(s) in conditioned media was then recorded by evaluating the ability of the
      spent media to direct granulosa cells (GC) steroidogenesis. METHODS: In order to
      obtain germ cells characterized by a different degree of developmental
      competence, selected pig oocytes from prepubertal gilts ovaries were cultured
      under different IVM protocols; part of the matured oocytes were used to produce
      OCM, while those remaining were submitted to in vitro fertilization trials to
      confirm their ability to sustain male pronuclear decondensation. The OCM
      collected were finally used on cumulus cells grown as monolayers for 5 days. The
      demonstration that oocytes secreted factor(s) can influence GC steroidogenesis in
      the pig was confirmed in our lab by studying E2 and P4 production by cumulus
      cells monolayers using a radioimmunoassay technique. RESULTS: Monolayers obtained
      by growing GC surrounding the oocytes for five days represent a tool, which is
      practical, stable and available in most laboratories; by using this bioassay, we
      detected the antiluteal effect of immature oocytes, and for the first time,
      demonstrated that properly matured germ cells are able to direct cumulus cells
      steroidogenesis by inhibiting E2 production (P < 0.01). Nevertheless, only fully
      competent oocytes were able to suppress estrogens production, while those
      cultured under unfavourable conditions were unable to exert any inhibitory effect
      on the functions of cumulus cells (P < 0.01). CONCLUSION: These results
      demonstrated that good quality oocytes can be easily selected on the basis of
      their ability to affect granulosa cell steroidogenesis thus reducing failures in
      reproductive technologies due to the transfer of fertilized oocytes with a scarce
      ability to sustain embryo development.

PMID- 12809558
TI  - Health-related quality of life, utility, and productivity outcomes instruments:
      ease of completion by subjects with COPD.
AB  - An important outcome of any clinical intervention is the change in the subject's
      own perceived state of health. This can be categorized as health-related quality
      of life (HRQL), utility (preference-based health state), and daily life
      performance. 174 Swedish subjects with chronic obstructive pulmonary disease
      (COPD) (mean age 64.3 PlusMinus; 12 years) completed five self-administered
      questionnaires: Short Form 36 (SF-36), St George's Respiratory Questionnaire
      (SGRQ), EuroQol-5D (EQ-5D), Health States-COPD (HS-COPD), and Work Productivity
      and Activity Impairment Questionnaire for COPD (WPAI-COPD). The subjects scored
      these outcomes instruments for ease of completion using a 5-point scale. The time
      taken to complete them was noted and the administrators' opinion of the subjects'
      comprehension of the questionnaires recorded using a 4-point scale. A score of 1
      3 ("very easy" to "acceptable") was recorded by 92% of subjects for the SF-36,
      90% for SGRQ, 80% for EQ-5D, 83% for WPAI-COPD, and 53% for HS-COPD. The HS-COPD
      was graded "very difficult" to complete by 21% of subjects compared with 3-5% of
      subjects for the other questionnaires. The mean time taken to complete all
      questionnaires was 39 minutes, and the large majority of subjects scored "good"
      for understanding by the administrator. Age correlated significantly with the
      degree of the subject's opinion of the ease of completion of five outcomes
      instruments, while the influence of gender, socio-economic status and disease
      severity was not statistically significant.

PMID- 12809559
TI  - Ethnic differences in allelic distribution of IFN-g in South African women but no
      link with cervical cancer.
AB  - BACKGROUND: The failure of specific types of human papillomaviruses (HPV) to
      raise effective immune responses may be important in the pathogenesis of cervical
      cancer, the second most common cancer in South African women. Polymorphisms of a
      number of cytokine genes have been implicated in inducing susceptibility or
      resistance to cancers caused by infectious agents owing to their role in
      determining host immune response. Polymorphisms of IL-10 and IFN-gamma genes are
      believed to influence the expression and/or secretion levels of their respective
      cytokines. METHODS AND RESULTS: In this study, women with histologically proven
      cancer of the cervix (n = 458) and hospital-based controls (n = 587) were
      investigated for bi-allelic -1082 (A/G) polymorphisms of IL-10 and the bi-allelic
      +874(A/T) polymorphisms of IFN-gamma. In addition, the distributions of the
      allelic frequencies were stratified in both the African and mixed race population
      groups of South Africa. We found striking differences in the allele distribution
      of IFN-gamma (X2 = 0.02) among the two ethnic groups. A significant increase in
      the allele distribution of the IFN-gamma AA genotype was found in the African
      group compared to the mixed population group (OR, 0.5; 95% CI, 0.2-1.0). For IL
      10 there were no significant allelic differences between the two South African
      ethnic groups. Furthermore, when the ethnic groups were combined the IL-10
      allelic frequencies in the combined South African data were similar to those
      observed in an Oriental population from Southern China and in an Italian
      population. However, the allele frequencies of the IFN-gamma genotype among the
      two South African ethnic groups were different when compared to an Italian
      Caucasoid group. While crude analysis of these data showed both statistically
      significantly increased and diminished risks of cervical cancer among high
      producers of INF-gamma and low producers of IL-10 respectively, these
      associations were no longer significant when the data were adjusted for
      confounding factors. CONCLUSION: These findings demonstrate a clear correlation
      between ethnicity and IFN-gamma polymorphism across different population groups.
      However, these differences in ethnicity and gene polymorphisms in the
      aforementioned cytokines are suggested not to influence the development of
      invasive cervical cancer but may represent an important susceptibility biomarker
      for other diseases and should be explored further.

PMID- 12809560
TI  - A tool for sharing annotated research data: the "Category 0" UMLS (Unified
      Medical Language System) vocabularies.
AB  - BACKGROUND: Large biomedical data sets have become increasingly important
      resources for medical researchers. Modern biomedical data sets are annotated with
      standard terms to describe the data and to support data linking between
      databases. The largest curated listing of biomedical terms is the the National
      Library of Medicine's Unified Medical Language System (UMLS). The UMLS contains
      more than 2 million biomedical terms collected from nearly 100 medical
      vocabularies. Many of the vocabularies contained in the UMLS carry restrictions
      on their use, making it impossible to share or distribute UMLS-annotated research
      data. However, a subset of the UMLS vocabularies, designated Category 0 by UMLS,
      can be used to annotate and share data sets without violating the UMLS License
      Agreement. METHODS: The UMLS Category 0 vocabularies can be extracted from the
      parent UMLS metathesaurus using a Perl script supplied with this article. There
      are 43 Category 0 vocabularies that can be used freely for research purposes
      without violating the UMLS License Agreement. Among the Category 0 vocabularies
      are: MESH (Medical Subject Headings), NCBI (National Center for Bioinformatics)
      Taxonomy and ICD-9-CM (International Classification of Diseases-9-Clinical
      Modifiers). RESULTS: The extraction file containing all Category 0 terms and
      concepts is 72,581,138 bytes in length and contains 1,029,161 terms. The UMLS
      Metathesaurus MRCON file (January, 2003) is 151,048,493 bytes in length and
      contains 2,146,899 terms. Therefore the Category 0 vocabularies, in aggregate,
      are about half the size of the UMLS metathesaurus.A large publicly available
      listing of 567,921 different medical phrases were automatically coded using the
      full UMLS metatathesaurus and the Category 0 vocabularies. There were 545,321
      phrases with one or more matches against UMLS terms while 468,785 phrases had one
      or more matches against the Category 0 terms. This indicates that when the two
      vocabularies are evaluated by their fitness to find at least one term for a
      medical phrase, the Category 0 vocabularies performed 86% as well as the complete
      UMLS metathesaurus. CONCLUSION: The Category 0 vocabularies of UMLS constitute a
      large nomenclature that can be used by biomedical researchers to annotate
      biomedical data. These annotated data sets can be distributed for research
      purposes without violating the UMLS License Agreement. These vocabularies may be
      of particular importance for sharing heterogeneous data from diverse biomedical
      data sets. The software tools to extract the Category 0 vocabularies are freely
      available Perl scripts entered into the public domain and distributed with this
      article.

PMID- 12809561
TI  - The postural effects of load carriage on young people--a systematic review.
AB  - BACKGROUND: Spinal pain in young people is a significant source of morbidity in
      industrialised countries. The carriage of posterior loads by young people has
      been linked with spinal pain, and the amount of postural change produced by load
      carriage has been used as a measure of the potential to cause tissue damage. The
      purpose of this review was to identify, appraise and collate the research
      evidence regarding load-carriage related postural changes in young people.
      METHODS: A systematic literature review sought published literature on the
      postural effects of load carriage in young people. Sixteen databases were
      searched, which covered the domains of allied health, childcare, engineering,
      health, health-research, health-science, medicine and medical sciences. Two
      independent reviewers graded the papers according to Lloyd-Smith's hierarchy of
      evidence scale. Papers graded between 1a (meta-analysis of randomised controlled
      trials) and 2b (well-designed quasi-experimental study) were eligible for
      inclusion in this review. These papers were quality appraised using a modified
      Crombie tool. The results informed the collation of research evidence from the
      papers sourced. RESULTS: Seven papers were identified for inclusion in this
      review. Methodological differences limited our ability to collate evidence.
      CONCLUSIONS: Evidence based recommendations for load carriage in young people
      could not be made based on the results of this systematic review, therefore
      constraining the use of published literature to inform good load carriage
      practice for young people.

PMID- 12809562
TI  - The disabilities of the arm, shoulder and hand (DASH) outcome questionnaire:
      longitudinal construct validity and measuring self-rated health change after
      surgery.
AB  - BACKGROUND: The disabilities of the arm, shoulder and hand (DASH) questionnaire
      is a self-administered region-specific outcome instrument developed as a measure
      of self-rated upper-extremity disability and symptoms. The DASH consists mainly
      of a 30-item disability/symptom scale, scored 0 (no disability) to 100. The main
      purpose of this study was to assess the longitudinal construct validity of the
      DASH among patients undergoing surgery. The second purpose was to quantify self
      rated treatment effectiveness after surgery. METHODS: The longitudinal construct
      validity of the DASH was evaluated in 109 patients having surgical treatment for
      a variety of upper-extremity conditions, by assessing preoperative-to
      postoperative (6-21 months) change in DASH score and calculating the effect size
      and standardized response mean. The magnitude of score change was also analyzed
      in relation to patients' responses to an item regarding self-perceived change in
      the status of the arm after surgery. Performance of the DASH as a measure of
      treatment effectiveness was assessed after surgery for subacromial impingement
      and carpal tunnel syndrome by calculating the effect size and standardized
      response mean. RESULTS: Among the 109 patients, the mean (SD) DASH score
      preoperatively was 35 (22) and postoperatively 24 (23) and the mean score change
      was 15 (13). The effect size was 0.7 and the standardized response mean 1.2.The
      mean change (95% confidence interval) in DASH score for the patients reporting
      the status of the arm as "much better" or "much worse" after surgery was 19 (15
      23) and for those reporting it as "somewhat better" or "somewhat worse" was 10 (7
      14) (p = 0.01). In measuring effectiveness of arthroscopic acromioplasty the
      effect size was 0.9 and standardized response mean 0.5; for carpal tunnel surgery
      the effect size was 0.7 and standardized response mean 1.0. CONCLUSION: The DASH
      can detect and differentiate small and large changes of disability over time
      after surgery in patients with upper-extremity musculoskeletal disorders. A 10
      point difference in mean DASH score may be considered as a minimal important
      change. The DASH can show treatment effectiveness after surgery for subacromial
      impingement and carpal tunnel syndrome. The effect size and standardized response
      mean may yield substantially differing results.

PMID- 12809563
TI  - r.hu-erythropoietin (EPO) treatment of pre-ESRD patients slows the rate of
      progression of renal decline.
AB  - BACKGROUND: As EPO treatment of chronic anemia of advanced renal disease is now
      the standard of care we examined if such treatment may slow the progression of
      renal function decline. METHODS: Data of 18 pre-ESRD patients were analyzed
      retrospectively 12 months prior and prospectively 12 months after the initiation
      of EPO. Mean creatinine was 5.0 +/- 1.8 mg/dL (Mean +/- SEM) when starting EPO at
      a weekly dose of 5000 +/- 500 units once the hematocrit was below 30 %. EPO dose
      was titrated monthly for a hematocrit between 33.0% and 37.0%. Metabolic
      complications and hypertension were controlled. RESULTS: At month_0 the average
      blood pressure was 148/76 +/- 5/4 mmHg and at month_12 it was 145/73 +/- 6/3 mmHg
      (p = 0.75 by 2 tailed paired Student's t test). 12/18 patients were on an ACE-i
      or ARB before month_0 and 14/18 were on it after (p = 0.71 by Fisher's 2 tailed
      exact test). The average hematocrit rose from 26.9% +/- 0.6 to 33.1 % +/- 0.1.
      When linear regression analysis was applied to pre- and post-EPO 1/creatinine
      data the mean rate of decline was -0.0140 +/- 0.0119 (mean +/- SD) and -0.0017 +/
      0.0090 (non-parametric Wilcoxon matched pairs signed rank sum test: Z value: 
      2.91; P = 0.004) respectively. 5/18 patients did not require dialysis 12 months
      after starting EPO (month_0). CONCLUSION: Treatment of the anemia of chronic
      renal failure with erythropoietin, when instituted together with vigorous
      metabolic control may slow the rate of renal function decline.

PMID- 12809564
TI  - Determinants for hospitalization in " low-risk" community acquired pneumonia.
AB  - BACKGROUND: A variable decision in managing community acquired pneumonia (CAP) is
      the initial site of care; in-patient versus outpatient. These variations persist
      despite comprehensive practice guidelines. Patients with a Pneumonia Severity
      Index (PSI) score lower than seventy have low risk for complications and
      outpatient antibiotic management is recommended in this group. These patients are
      generally below the age of fifty years, non-nursing home residents, HIV negative
      and have no major cardiac, hepatic, renal or malignant diseases. METHODS: A
      retrospective analysis of 296 low-risk CAP patients evaluated within a year one
      period at St. Agnes Hospital, Baltimore, Maryland was undertaken. All patients
      were assigned a PSI score. 208 (70%) were evaluated and discharged from the
      emergency department (E.D.) to complete outpatient antibiotic therapy, while 88
      (30%) were hospitalized. Patients were sub-stratified into classes I-V according
      to PSI. A comparison of demographic, clinical, social and financial parameters
      was made between the E.D. discharged and hospitalized groups. RESULTS:
      Statistically significant differences in favor of the hospitalized group were
      noted for female gender (CI: 1.46-5.89, p= 0.0018), African Americans (CI: 0.31
      0.73, p= 0.004), insurance coverage (CI: 0.19-0.63, p= 0.0034), temperature (CI:
      0.04-0.09, p= 0.0001) and pulse rate (CI: 0.03-0.14, p= 0.0001). No statistically
      significant differences were observed between the two groups for altered mental
      status, hypotension, tachypnea, laboratory/radiological parameters and social
      indicators (p>0.05). The average length of stay for in-patients was 3.5 days at
      about eight time's higher cost than outpatient management. There was no
      difference in mortality or treatment failures between the two groups. The
      documentation rate and justifications for hospitalizing low risk CAP patients by
      admitting physicians was less than optimal. CONCLUSIONS: High fever, tachycardia,
      female gender, African- American race and medical insurance coverage are
      determinants for hospitalization among low risk CAP patients in our study. The
      average length of stay for in-patients was 3.5 days (3 to 5 days). The cost of in
      patient care was about eight times higher than outpatient management. This study
      supports the recommendation of using the PSI for E.D evaluation of patients in
      appropriate social settings.

PMID- 12809565
TI  - Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells.
AB  - BACKGROUND: Fanconi anemia (FA) is a complex recessive genetic disease
      characterized by progressive bone marrow failure (BM) and a predisposition to
      cancer. We have previously shown using the Fancc mouse model that the progressive
      BM failure results from a hematopoietic stem cell defect suggesting that function
      of the FA genes may reside in primitive hematopoietic stem cells. METHODS: Since
      genes involved in stem cell differentiation and/or maintenance are usually
      regulated at the transcription level, we used a semiquantitative RT-PCR method to
      evaluate FA gene transcript levels in purified hematopoietic stem cells. RESULTS:
      We show that most FA genes are highly expressed in primitive CD34-positive and
      negative cells compared to lower levels in more differentiated cells. However, in
      CD34- stem cells the Fancc gene was found to be expressed at low levels while
      Fancg was undetectable in this population. Furthermore, Fancg expression is
      significantly decreased in Fancc -/- stem cells as compared to wild-type cells
      while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in
      Fancc-/- hematopoietic cells. CONCLUSIONS: These results suggest that FA genes
      are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+
      cells correlates with a role at the CD34+ differentiation stage and that lack of
      Fancc affects the expression of other FA gene, more specifically Fancg and
      Fancd1/Brca2, through an unknown mechanism.

PMID- 12809566
TI  - Randomized trials, generalizability, and meta-analysis: graphical insights for
      binary outcomes.
AB  - BACKGROUND: Randomized trials stochastically answer the question. "What would be
      the effect of treatment on outcome if one turned back the clock and switched
      treatments in the given population?" Generalizations to other subjects are
      reliable only if the particular trial is performed on a random sample of the
      target population. By considering an unobserved binary variable, we graphically
      investigate how randomized trials can also stochastically answer the question,
      "What would be the effect of treatment on outcome in a population with a possibly
      different distribution of an unobserved binary baseline variable that does not
      interact with treatment in its effect on outcome?" METHOD: For three different
      outcome measures, absolute difference (DIF), relative risk (RR), and odds ratio
      (OR), we constructed a modified BK-Plot under the assumption that treatment has
      the same effect on outcome if either all or no subjects had a given level of the
      unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary
      covariate on a binary outcome in two treatment groups; it was originally
      developed to explain Simpsons's paradox.) RESULTS: For DIF and RR, but not OR,
      the BK-Plot shows that the estimated treatment effect is invariant to the
      fraction of subjects with an unobserved binary variable at a given level.
      CONCLUSION: The BK-Plot provides a simple method to understand generalizability
      in randomized trials. Meta-analyses of randomized trials with a binary outcome
      that are based on DIF or RR, but not OR, will avoid bias from an unobserved
      covariate that does not interact with treatment in its effect on outcome.

PMID- 12809567
TI  - The protective effect of M40401, a superoxide dismutase mimetic, on post-ischemic
      brain damage in Mongolian gerbils.
AB  - BACKGROUND: Overproduction of free radical species has been shown to occur in
      brain tissues after ischemia-reperfusion injury. However, most of free radical
      scavengers known to antagonize oxidative damage (e.g. superoxide dismutase,
      catalase), are unable to protect against ischemia-reperfusion brain injury when
      given in vivo, an effect mainly due to their difficulty to gain access to brain
      tissues. Here we studied the effect of a low molecular weight superoxide
      dismutase mimetic (M40401) in brain damage subsequent to ischemia-reperfusion
      injury in Mongolian gerbils. RESULTS: In animals undergoing ischemia-reperfusion
      injury, neuropathological and ultrastructural changes were monitored for 1-7 days
      either in the presence or in the absence of M40401 after bilateral common carotid
      artery occlusion (BCCO). Administration of M40401 (1-40 mg/kg, given i.p. 1 h
      after BCCO) protected against post-ischemic, ultrastructural and
      neuropathological changes occurring within the hippocampal CA1 area. The
      protective effect of M40401 was associated with a significant reduction of the
      levels of malondialdehyde (MDA; a marker of lipid peroxidation) in ischemic brain
      tissues after ischemia-reperfusion. CONCLUSION: Taken together, these results
      demonstrate that M40401 provides protective effects when given early after the
      induction of ischemia-reperfusion of brain tissues and suggest the possible use
      of such compounds in the treatment of neurological dysfunction subsequent to
      cerebral flow disturbances.

PMID- 12809568
TI  - Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis
      and M. tuberculosis.
AB  - BACKGROUND: Tuberculosis remains a serious world-wide health threat which
      requires the characterisation of novel drug targets for the development of future
      antimycobacterials. One of the key obstacles in the definition of new targets is
      the large variety of metabolic alterations that occur between cells in the active
      growth and chronic/dormant phases of tuberculosis. The ideal biochemical target
      should be active in both growth phases. Methionine adenosyltransferase, which
      catalyses the formation of S-adenosylmethionine from methionine and ATP, is
      involved in polyamine biosynthesis during active growth and is also required for
      the methylation and cyclopropylation of mycolipids necessary for survival in the
      chronic phase. RESULTS: The gene encoding methionine adenosyltransferase has been
      cloned from Mycobacterium tuberculosis and the model organism M. smegmatis. Both
      enzymes retained all amino acids known to be involved in catalysing the reaction.
      While the M. smegmatis enzyme could be functionally expressed, the M.
      tuberculosis homologue was insoluble and inactive under a large variety of
      expression conditions. For the M. smegmatis enzyme, the Vmax for S
      adenosylmethionine formation was 1.30 micromol/min/mg protein and the Km for
      methionine and ATP was 288 microM and 76 microM respectively. In addition, the
      enzyme was competitively inhibited by 8-azaguanine and azathioprine with a Ki of
      4.7 mM and 3.7 mM respectively. Azathioprine inhibited the in vitro growth of M.
      smegmatis with a minimal inhibitory concentration (MIC) of 500 microM, while the
      MIC for 8-azaguanine was >1.0 mM. CONCLUSION: The methionine adenosyltransferase
      from both organisms had a primary structure very similar those previously
      characterised in other prokaryotic and eukaryotic organisms. The kinetic
      properties of the M. smegmatis enzyme were also similar to known prokaryotic
      methionine adenosyltransferases. Inhibition of the enzyme by 8-azaguanine and
      azathioprine provides a starting point for the synthesis of higher affinity
      purine-based inhibitors.

PMID- 12809569
TI  - [Fulminant hepatic failure and liver transplantation. Experience of the Hospital
      Virgen de la Arrixaca].
AB  - INTRODUCTION: Medical treatment for fulminat hepatic failure seeks spontaneous
      recovery of the liver function, but the results are very discouraging (50-80%
      mortality). Liver transplantation is an option in patients with a poor evolution
      despite medical treatment, with survival rates of > 50%. The ideal moment for
      performing the transplant is controversial, as it should not be done too soon,
      when the liver disease is still reversible, or tool late, when the patient is in
      an irreversible clinical situation. PATIENTS AND METHOD: A retrospective review
      was made of the clinical histories of 34 patients admitted to our hospital with a
      diagnosis of fulminant hepatic failure, of whom 26 underwent transplantation. The
      most frequent cause was viral, with 10 cases (38%); no aetiology at all could be
      established in 11 cases (42%). Thirteen patients had preoperative complications,
      the most frequent being renal insufficiency. As for degree of ABO/DR
      compatibility, 13 cases were identical (40%), 17 compatible (51%) and the other 3
      incompatible (9%). RESULTS: Thirty-three transplants were performed in 26
      patients: 4 were retransplants due to chronic rejection, 2 for primary graft
      failure and 1 for hyperacute rejection. The overall mortality rate was 46% (12
      patients), the most frequent cause of death being infection (50%). The overall
      actuarial survival rate was 68% at 1 year, 63% at 3 years and 59% at 5 years. The
      factors of poor prognosis were renal and respiratory insufficiency, a grade D
      electroencephalogram, and encephalopathy grades III and IV, the latter being the
      only prognostic factor identified in the multivariate analysis. The prognostic
      factors for mortality were a grade D electroencephalogram, encephalopathy grades
      III and IV and respiratory insufficiency, the latter being the only prognostic
      factor identified in the multivariate analysis. CONCLUSIONS: The achievement of
      good results with the use of transplantation in the management of fulminant
      hepatic failure depends on an optimum selection of transplant candidates, which
      means identifying them early, i.e. early indication for transplant, reduction in
      mean waiting time and exclusion of factors of poor prognosis.

PMID- 12809570
TI  - [Gastrointestinal anisakiasis. Study of a series of 25 patients].
AB  - INTRODUCTION: Infection with the parasite Anisakis simplex is common in Japan and
      northern European countries. The number of reported cases in Spain has increased
      since the first description in 1991. The aim of the present study was to evaluate
      the incidence, clinical patterns, histopathological lesions, treatment, and
      outcome of Anisakis simplex infection in our environment. MATERIAL AND METHOD:
      Cases of gastrointestinal anisakiasis diagnosed in our center from December 1999
      to January 2002 were studied. Only patients with detection of the parasite in
      oral endoscopy or the surgical specimen and those with elevated levels of
      specific IgE to Anisakis simplex, a clinical picture compatible with anisakiasis,
      or a history of raw fish intake were included. Epidemiological, clinical and
      laboratory data, as well as diagnostic, histopathologic and therapeutic features,
      and outcome in these patients were recorded. RESULTS: Twenty-five cases of
      gastrointestinal anisakiasis were diagnosed during the study period, representing
      an incidence of 3.87 cases per 100 000 inhabitants/year. All the patients had
      ingested raw anchovies. Two groups were observed. The first group was composed of
      10 patients with a gastric form of the infection, in which the main symptom was
      epigastralgia (90%). Oral endoscopy was performed in all patients and the
      parasite was detected in five (50%). The second group was composed of 15 patients
      with intestinal involvement in which the main manifestations were symptoms
      mimicking appendicitis (80%). The most frequent finding of laparotomy and/or
      imaging tests (abdominal ultrasonography, intestinal transit, abdominal CAT) was
      terminal ileitis (80%). Seven patients underwent surgery: intestinal resection
      was performed in four with detection of Anisakis simplex in three. Eosinophilic
      infiltration was found in all surgical specimens. Treatment was symptomatic in
      most of the patients and outcome was favorable in all. CONCLUSIONS: Infection
      with Anisakis simplex should be investigated in patients with abdominal pain
      after intake of raw fish, ileitis of unclear origin, or eosinophilic
      gastroenteritis.

PMID- 12809572
TI  - [Intestinal tuberculosis. A diagnostic challenge].
AB  - Tuberculosis (TB) is a common disease in Spain, whose incidence has increased due
      to AIDS, immunotherapy and immigration. Intestinal disease is rare and can be
      difficult to diagnose because its symptoms and laboratory results are
      nonspecific. In addition, endoscopic lesions resemble those of other diseases
      such as Crohns disease (CD). Differentiating between intestinal TB and CD is very
      important since steroid treatment con be life saving in CD and lethal in
      intestinal TB. Colonoscopy plays an important role in establishing a suspected
      diagnosis. The endoscopic findings most characteristic of intestinal TB are
      circular ulcers, small diverticula (3-5 mm), and sessile firm polyps. The
      suspected diagnosis must be confirmed by the presence of caseating granulomas
      and/or acid fast bacilli. Polymerase chain reaction is currently recommended for
      assessing the presence of tubercle bacilli in tissue specimens obtained by
      endoscopic biopsy. We report a case of intestinal TB in a female renal transplant
      recipient that demonstrates the difficulty of making this diagnosis.

PMID- 12809571
TI  - [Granulocytic sarcoma (chloroma) of small bowel: an unfrequent cause of
      intestinal obstruction].
AB  - Granulocytic sarcoma or chloroma is a malignant extra medullar tumor, based on
      inmature myeloid cells. It usually emerges as a secondary manifestation of acute
      myeloid leukemia. Chloromas are scarcely diagnosed in patiens without
      hematological malignances, either peripheral or medullar, and are thus frequently
      misdiagnosed for other tumors. In these patients, further development of acute
      leukemia seems to stand as a rule. Small bowel location of these tumors has
      hardly been reported. A case of granulocytic sarcoma in a non-leukemic at time of
      diagnosis patient is reported therein. Medical literature is briefly reviewed.

PMID- 12809573
TI  - [Consensus document on indications for liver transplantation. 2002].

PMID- 12809574
TI  - [Solitary rectal ulcer inflammation, infection, ischemia or motor disorder?].

PMID- 12809575
TI  - [Fibrogenesis and liver transplantation].

PMID- 12809576
TI  - [An infrequent presentation of Gemella morbillorum infection: liver abscess].

PMID- 12809577
TI  - [Primary hemochromatosis with abnormally low serum ferritin].

PMID- 12809578
TI  - [Follicular lymphoid hyperplasia, IgA deficiency and coinfecction of Giardia
      lamblia and Epstein-Barr virus].

PMID- 12809579
TI  - [Hepato-gastric tuberculosis: a rare association].

PMID- 12809580
TI  - [The multiple faces of the control of tuberculosis].

PMID- 12809581
TI  - [Study investigating infection in contacts of tuberculosis patients in a semi
      urban area].
AB  - INTRODUCTION: The most important factors for establishing priorities in studies
      of contacts are the bacteriological status of the patient and the degree of
      exposure of contact persons to the index case. The aim of the present study was
      to analyze the results of tuberculosis contact tracing and the relationship
      between these results and the bacteriological situation of the index case and the
      proximity of exposure. METHODS: We studied the contacts of tuberculosis cases
      examined in the Center for Tuberculosis Control and Prevention of Lleida (a city
      in the autonomous region of Catalonia, Spain) over the period 1991-1997. The
      Mantoux test with 2 TU of PPD-RT23 was used to identify infected persons.
      Diagnosis of tuberculosis disease was made on evidence from the clinical
      situation, chest radiography and bacteriological status. Associations between
      infection or disease in the contact, and the bacteriological status of the index
      case and proximity of exposure, were analyzed. The chi-square test was used for
      statistical analyses; significance was set at a p value of, 0.05. The odds ratio
      was calculated as a measure of association. RESULTS: The prevalence of
      tuberculosis infection among the contacts was 44% (763/1733). Tuberculin
      conversion was observed in 7.8% of contacts, and 31 new cases of tuberculosis
      were detected (1.8%). The percentages of tuberculosis infection, tuberculin
      conversion and case detection were higher among persons exposed to sputum smear
      positive patients and among those in close contact with the index case. Contact
      infection was more highly associated with the bacteriological status of the index
      case and degree of proximity of exposure when the analysis was restricted to
      contacts less than 15 years old. Case detection was 4% among close contacts
      living with a sputum smear-positive patient. CONCLUSIONS: Investigation into
      tuberculosis contacts offered a high yield of detection of infected contact
      persons and new tuberculosis cases, even among contacts of culture-negative
      pulmonary tuberculosis patients and contacts of extrapulmonary tuberculosis
      patients.

PMID- 12809582
TI  - [Randomized trial of three regimens to prevent tuberculosis in HIV-infected
      patients with anergy].
AB  - INTRODUCTION: To evaluate the efficacy of three regimens of prophylactic therapy
      for tuberculosis in HIV-infected patients with anergy. METHODS: Prospective,
      multi-center, randomized, comparative, and open clinical trial. Anergy was
      defined as absence of induration in response to three antigens (PPD, Candida
      albicans and parotiditis antigen) applied by the Mantoux method. Patients were
      randomized into one of the following prophylactic treatment groups: isoniazid for
      six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus
      pyrazinamide for two months (2RZ) or no treatment (NT). After completion of
      treatment, patients were followed up for two years. RESULT: A total of 319
      patients were included in the study, 83 in the 6H regimen, 82 in 3RH, 77 in 2RZ
      and 77 in NT. The observation period following treatment was 88, 96, 81 and 126
      person-years, respectively, for 6H, 3RH, 2RZ and NT. There were 11 cases of
      tuberculosis during the follow-up period. The tuberculosis rates (cases per 100
      person-years) were 3.4, 3.1, 1.2 and 3.1 for 6H, 3RH, 2RZ and NT respectively,
      with relative risks in regimens 6H, 3RH and 2RZ with respect to NT of 1.07 (0.24
      4.80), 0.98 (0.22-4.4) and 0.39 (0.04-3.48), all statistically non-significant.
      Twenty-nine patients died during the follow-up period, none due to tuberculosis,
      and no appreciable differences were found among the groups. CONCLUSIONS: The
      results showed no significant decrease in the risk of developing tuberculosis
      with any of the evaluated regimens and, therefore, do not support the use of
      antituberculosis chemoprophylaxis in anergic HIV-infected patients.

PMID- 12809583
TI  - [Directly observed treatment of latent tuberculosis infection: comparative study
      of two isoniazid regimens].
AB  - INTRODUCTION: To compare compliance with two isoniazid regimens in drug users
      with latent tuberculosis infection. METHODS. DESIGN: clinical trial. Group 1:
      isoniazid 300 mg once daily (16 patients); Group 2: isoniazid 900 mg/twice weekly
      (21). ENDPOINTS: compliance, toxicity and efficacy. RESULTS: Group 1 vs. Group 2:
      continuation in program 81/82% (p 5 NS), compliance full doses 43.7/66.6% (p 5
      0.1), median percentage of days not taking isoniazid: 1.8 (0.2-4.3) vs. 0 (0-1.7)
      (p 5 0.06). CONCLUSIONS: Compliance was high in both therapeutic arms. The twice
      weekly isoniazid regimen favored compliance, but differences were not
      significant.

PMID- 12809584
TI  - [What terms can be applied to mycobacteria other than M. tuberculosis and M.
      leprae].
AB  - A review of the terms used to name mycobacteria other than M. tuberculosis and M.
      leprae was performed. A system using binomial nomenclature is defended. The
      author comments on the various names applied to mycobacteria over the history of
      medicine, from 1899 to the present, and the reasons why terms such as
      environmental mycobacteria or nontuberculous mycobacteria are incorrect and
      should not be used. In the case that a general name must be chosen for these
      mycobacteria, the term atypical mycobacteria is advocated.

PMID- 12809585
TI  - [Drugs with activity against Mycobacterium tuberculosis].
AB  - Treatment for Mycobacterium tuberculosis has to be lengthy, since populations of
      this bacillus differ in metabolic activity, and it has to consist of various
      associated drugs, since spontaneous chromosome mutations can give rise to drug
      resistance. The multiresistant phenotype emerges with sequential acquisition of
      mutations in several loci of separate genes. Knowledge of the mechanisms of
      resistance permits the development of molecular techniques for the early
      detection of resistant strains, thereby making proper control possible.
      Tuberculosis treatment includes isoniazid, rifampicin and pyrazinamide during the
      first two months and isoniazid and rifampicin to complete six months of
      treatment. In specific situations, a fourth drug is added, ethambutol for adults
      and streptomycin for children in whom visual acuity cannot be monitored. This
      review describes the characteristics, activity, resistance mechanisms and side
      effects associated with the various antituberculosis drugs.

PMID- 12809586
TI  - [Defining AIDS terminology. A practical approach].
AB  - Since the appearance of AIDS, the study of this disease has generated a large
      amount of information and an extensive related vocabulary comprised of new terms
      or terms borrowed from other scientific fields. The urgent need to provide names
      for newly described phenomena and concepts in this field has resulted in the
      application of terms that are not always appropriate from the linguistic and
      scientific points of view. We discuss the difficulties in attempting to create
      adequate AIDS terminology in the Spanish language, considering both the general
      problems involved in building any scientific vocabulary and the specific problems
      inherent to this activity in a field whose defining illness has important social
      connotations. The pressure exerted by the predominance of the English language in
      reporting scientific knowledge is considered, and the inappropriate words most
      often found in a review of current literature are examined. Finally, attending to
      the two most important criteria for the creation of new scientific terms,
      accuracy and linguistic correction, we propose some well thought-out alternatives
      that conform to the essence of the Spanish language.

PMID- 12809587
TI  - [Hypogastric colic pain and eosinophilia in a patient from the Gambia].

PMID- 12809588
TI  - [Acute maxillary sinusitis in a patient with VIH infection].

PMID- 12809589
TI  - [Primary abscess of the psoas due to Salmonella enterica, serogroup G, serotype
      friedenau].

PMID- 12809590
TI  - [Early post-exposure diagnosis of HIV infection].

PMID- 12809591
TI  - [Detection of antibodies against teichoic acids (Endo-Staph Teichoic Acid
      Antibody Test, Meridian Diagnostic) in deep Staphylococcus aureus infections].

PMID- 12809592
TI  - [Linezolid-induced anemia].

PMID- 12809593
TI  - [Cholestatic hepatitis due to amoxicillin-clavulanic acid with positive re
      exposure].

PMID- 12809594
TI  - [Acute abdomen due to Anisakis simplex].

PMID- 12809595
TI  - [Compliance with antiretroviral treatment. Prevalence study in a general
      hospital].

PMID- 12809596
TI  - [Acute bacterial parotiditis due to methicillin-resistant Staphylococcus aureus
      in the institutionalized elderly].

PMID- 12809597
TI  - The flowers that bloom in the spring: RNA processing and seasonal flowering.
AB  - Seasonal flowering in plants responds to hormonal and environmental cues that
      lead to expression of genes for flowering and growth. A new paper in this issue
      of Cell describes how one regulatory gene controls its own expression at the
      level of mRNA polyadenylation, adding an exciting new model for both the RNA
      processing and plant gene expression fields.

PMID- 12809598
TI  - MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing.
AB  - Drosophila geneticists have uncovered roles for microRNAs in the coordination of
      cell proliferation and cell death during development, and in stress resistance
      and fat metabolism. In C. elegans, a homolog of the well-known fly developmental
      regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway
      controlling developmental timing.

PMID- 12809599
TI  - PARP goes transcription.
AB  - PARP-1, an enzyme that catalyzes the attachment of ADP ribose units to target
      proteins, plays at least two important roles in transcription regulation. First,
      PARP-1 modifies histones and creates an anionic poly(ADPribose) matrix that binds
      histones, thereby promoting the decondensation of higher-order chromatin
      structures. Second, PARP-1 acts as a component of enhancer/promoter regulatory
      complexes. Recent studies have shown that both of these activities are critical
      for gene regulation in vivo.

PMID- 12809600
TI  - Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
AB  - TGF-beta signaling controls a plethora of cellular responses and figures
      prominently in animal development. Recent cellular, biochemical, and structural
      studies have revealed significant insight into the mechanisms of the activation
      of TGF-beta receptors through ligand binding, the activation of Smad proteins
      through phosphorylation, the transcriptional regulation of target gene
      expression, and the control of Smad protein activity and degradation. This
      article reviews these latest advances and presents our current understanding on
      the mechanisms of TGF-beta signaling from cell membrane to the nucleus.

PMID- 12809601
TI  - mRNA cap-1 methyltransferase in the SARS genome.
AB  - The 3D jury system has predicted the methyltransferase fold for the nsp13 protein
      of the SARS coronavirus. Based on the conservation of a characteristic tetrad of
      residues, the mRNA cap-1 methyltransferase function has been assigned to this
      protein, which has potential implications for antiviral therapy.

PMID- 12809602
TI  - Rb-mediated heterochromatin formation and silencing of E2F target genes during
      cellular senescence.
AB  - Cellular senescence is an extremely stable form of cell cycle arrest that limits
      the proliferation of damaged cells and may act as a natural barrier to cancer
      progression. In this study, we describe a distinct heterochromatic structure that
      accumulates in senescent human fibroblasts, which we designated senescence
      associated heterochromatic foci (SAHF). SAHF formation coincides with the
      recruitment of heterochromatin proteins and the retinoblastoma (Rb) tumor
      suppressor to E2F-responsive promoters and is associated with the stable
      repression of E2F target genes. Notably, both SAHF formation and the silencing of
      E2F target genes depend on the integrity of the Rb pathway and do not occur in
      reversibly arrested cells. These results provide a molecular explanation for the
      stability of the senescent state, as well as new insights into the action of Rb
      as a tumor suppressor.

PMID- 12809603
TI  - Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of
      a lipid attraction signal.
AB  - Efficient engulfment of the intact cell corpse is a critical end point of
      apoptosis, required to prevent secondary necrosis and inflammation. The
      presentation of "eat-me" signals on the dying cell is an important part of this
      process of recognition and engulfment by professional phagocytes. Here, we
      present evidence that apoptotic cells secrete chemotactic factor(s) that
      stimulate the attraction of monocytic cells and primary macrophages. The
      activation of caspase-3 in the apoptotic cell was found to be required for the
      release of this chemotactic factor(s). The putative chemoattractant was
      identified as the phospholipid, lysophosphatidylcholine. Further analysis showed
      that lysophosphatidylcholine was released from apoptotic cells due to the caspase
      3 mediated activation of the calcium-independent phospholipase A(2). These data
      suggest that in addition to eat-me signals, apoptotic cells display attraction
      signals to ensure the efficient removal of apoptotic cells and prevent
      postapoptotic necrosis.

PMID- 12809604
TI  - The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid
      signaling pathway.
AB  - Ecdysteroid pulses trigger the major developmental transitions during the
      Drosophila life cycle. These hormonal responses are thought to be mediated by the
      ecdysteroid receptor (EcR) and its heterodimeric partner Ultraspiracle (USP). We
      provide evidence for a second ecdysteroid signaling pathway mediated by DHR38,
      the Drosophila ortholog of the mammalian NGFI-B subfamily of orphan nuclear
      receptors. DHR38 also heterodimerizes with USP, and this complex responds to a
      distinct class of ecdysteroids in a manner that is independent of EcR. This
      response is unusual in that it does not involve direct binding of ecdysteroids to
      either DHR38 or USP. X-ray crystallographic analysis of DHR38 reveals the absence
      of both a classic ligand binding pocket and coactivator binding site, features
      that seem to be common to all NGFI-B subfamily members. Taken together, these
      data reveal the existence of a separate structural class of nuclear receptors
      that is conserved from fly to humans.

PMID- 12809605
TI  - A kinesin, invA, plays an essential role in volvox morphogenesis.
AB  - In Volvox carteri adults, reproductive cells called gonidia are enclosed within a
      spherical monolayer of biflagellate somatic cells. Embryos must "invert" (turn
      inside out) to achieve this configuration, however, because at the end of
      cleavage the gonidia are on the outside and the flagellar ends of all somatic
      cells point inward. Generation of a bend region adequate to turn the embryo
      inside out involves a dramatic change in cell shape, plus cell movements. Here,
      we cloned a gene called invA that is essential for inversion and found that it
      codes for a kinesin localized in the cytoplasmic bridges that link all cells to
      their neighbors. In invA null mutants, cells change shape normally, but are
      unable to move relative to the cytoplasmic bridges. A normal bend region cannot
      be formed and inversion stops. We conclude that the InvA kinesin provides the
      motile force that normally drives inversion to completion.

PMID- 12809606
TI  - Drosophila clock can generate ectopic circadian clocks.
AB  - Circadian rhythms of behavior, physiology, and gene expression are present in
      diverse tissues and organisms. The function of the transcriptional activator,
      Clock, is necessary in both Drosophila and mammals for the expression of many
      core clock components. We demonstrate in Drosophila that Clock misexpression in
      nai;ve brain regions induces circadian gene expression. This includes major
      components of the pacemaker program, as Clock also activates the rhythmic
      expression of cryptochrome, a gene that CLOCK normally represses. Moreover, this
      ectopic clock expression has potent effects on behavior, radically altering
      locomotor activity patterns. We propose that Clock is uniquely able to induce and
      organize the core elements of interdependent feedback loops necessary for
      circadian rhythms.

PMID- 12809607
TI  - Control of cell morphogenesis in bacteria: two distinct ways to make a rod-shaped
      cell.
AB  - Cell shape in most eubacteria is maintained by a tough external peptidoglycan
      cell wall. Recently, cell shape determining proteins of the MreB family were
      shown to form helical, actin-like cables in the cell. We used a fluorescent
      derivative of the antibiotic vancomycin as a probe for nascent peptidoglycan
      synthesis in unfixed cells of various Gram-positive bacteria. In the rod-shaped
      bacterium B. subtilis, synthesis of the cylindrical part of the cell wall occurs
      in a helical pattern governed by an MreB homolog, Mbl. However, a few rod-shaped
      bacteria have no MreB system. Here, a rod-like shape can be achieved by a
      completely different mechanism based on use of polar growth zones derived from
      the division machinery. These results provide insights into the diverse molecular
      strategies used by bacteria to control their cellular morphology, as well as
      suggesting ways in which these strategies may impact on growth rates and cell
      envelope structure.

PMID- 12809608
TI  - FY is an RNA 3' end-processing factor that interacts with FCA to control the
      Arabidopsis floral transition.
AB  - The nuclear RNA binding protein, FCA, promotes Arabidopsis reproductive
      development. FCA contains a WW protein interaction domain that is essential for
      FCA function. We have identified FY as a protein partner for this domain. FY
      belongs to a highly conserved group of eukaryotic proteins represented in
      Saccharomyces cerevisiae by the RNA 3' end-processing factor, Pfs2p. FY regulates
      RNA 3' end processing in Arabidopsis as evidenced through its role in FCA
      regulation. FCA expression is autoregulated through the use of different
      polyadenylation sites within the FCA pre-mRNA, and the FCA/FY interaction is
      required for efficient selection of the promoter-proximal polyadenylation site.
      The FCA/FY interaction is also required for the downregulation of the floral
      repressor FLC. We propose that FCA controls 3' end formation of specific
      transcripts and that in higher eukaryotes, proteins homologous to FY may have
      evolved as sites of association for regulators of RNA 3' end processing.

PMID- 12809609
TI  - Study of the structural dynamics of the E coli 70S ribosome using real-space
      refinement.
AB  - Cryo-EM density maps showing the 70S ribosome of E. coli in two different
      functional states related by a ratchet-like motion were analyzed using real-space
      refinement. Comparison of the two resulting atomic models shows that the ribosome
      changes from a compact structure to a looser one, coupled with the rearrangement
      of many of the proteins. Furthermore, in contrast to the unchanged inter-subunit
      bridges formed wholly by RNA, the bridges involving proteins undergo large
      conformational changes following the ratchet-like motion, suggesting an important
      role of ribosomal proteins in facilitating the dynamics of translation.

PMID- 12809610
TI  - DNA deamination mediates innate immunity to retroviral infection.
AB  - CEM15/APOBEC3G is a cellular protein required for resistance to infection by
      virion infectivity factor (Vif)-deficient human immunodeficiency virus (HIV).
      Here, using a murine leukemia virus (MLV)-based system, we provide evidence that
      CEM15/APOBEC3G is a DNA deaminase that is incorporated into virions during viral
      production and subsequently triggers massive deamination of deoxycytidine to
      deoxyuridine within the retroviral minus (first)-strand cDNA, thus providing a
      probable trigger for viral destruction. Furthermore, HIV Vif can protect MLV from
      this CEM15/APOBEC3G-dependent restriction. These findings imply that targeted DNA
      deamination is a major strategy of innate immunity to retroviruses and likely
      also contributes to the sequence variation observed in many viruses (including
      HIV).

PMID- 12809612
TI  - Statistical methods for chip calibration and saturation effects in antibody
      spiked gene expression data.
AB  - Oligonucleotide microarrays are amongst, a set of technologies that allow for
      high throughput assessment of vast numbers of gene expressions. In order to
      evaluate gene expressions given detection limits, antibody spiking is often used
      providing one with an expression curve relating antibody treated expression and
      non-antibody treated expression. These curves can exhibit different functional
      shapes across chips and hence need to be standardized. In addition, each curve is
      subject to saturation effects, which are typically dealt with by extrapolating a
      linear fit to the subset of the data not visually subject to saturation. In this
      paper we introduce methods for the non-parametric standardization of expression
      curves using univariate smoothers. We also explore parametric methods for more
      efficient analysis of the standardized curves. We demonstrate an alternate method
      of parametric analysis using a weighted linear mixed effects model that does not
      arbitrarily delete data beyond an observed saturation point; allows for natural
      grouping of genes and provides significantly more accurate predictions than naive
      linear extrapolation. Both methodologies are studied through sets of simulations.

PMID- 12809613
TI  - Developmental molecular switches regulating breathing patterns in CNS.
AB  - The present paper presents some of the molecular switches that may operate at
      early embryonic stages to make development of the brainstem respiratory rhythm
      generator a robust and irreversible process. We concentrate on the role of
      transient Hox-related gene expression patterns in register with the
      regionalisation of the rhombencephalic neural tube along the antero-posterior
      axis. Using different recording and isolation procedures in chick embryos, we
      show that the hindbrain is subdivided at E1 into developmental units
      (rhombomeres) intrinsically able to produce rhythm generating neuronal circuits
      active at E5. At E6, intrinsic cues also allow a progressive maturation of
      episodic rhythm generators that persists after isolation of the hindbrain in
      vitro and requires odd/even rhombomeric interactions at E1. From these results
      and from respiratory pathologies observed in transgenic mice, we are beginning to
      understand that, despite diversity of breathing patterns and adaptations, there
      are links between developmental control genes and adult respiration.

PMID- 12809614
TI  - Dopaminergic mechanisms of neural plasticity in respiratory control: transgenic
      approaches.
AB  - Data supporting the hypothesis that dopamine-2 receptors (D(2)-R) contribute to
      time-dependent changes in the hypoxic ventilatory response (HVR) during
      acclimatization to hypoxia are briefly reviewed. Previous experiments with
      transgenic animals (D(2)-R 'knockout' mice) support this hypothesis (J. Appl.
      Physiol. 89 (2000) 1142). However, those experiments could not determine (1) if
      D(2)-R in the carotid body, the CNS, or both were involved, or (2) if D(2)-R were
      necessary during the acclimatization to hypoxia versus some time prior to chronic
      hypoxia, e.g. during a critical period of development. Additional experiments on
      C57BL/6J mice support the idea that D(2)-R are critical during the period of
      exposure to hypoxia for normal ventilatory acclimatization. D(2)-R in carotid
      body chemoreceptors predominate under control conditions to inhibit normoxic
      ventilation, but excitatory effects of D(2)-R, presumably in the CNS, predominate
      after acclimatization to hypoxia. The inhibitory effects of D(2)-R in the carotid
      body are reset to operate primarily under hypoxic conditions in acclimatized
      rats, thereby optimizing O(2)-sensitivity.

PMID- 12809615
TI  - Tachykinins in the control of breathing by hypoxia: pre- and post-genomic era.
AB  - This article highlights major findings from physiological and pharmacological
      studies conducted in the pre- and post-genomic era examining the roles of
      substance P (SP) and other tachykinins in the response of the carotid body to
      hypoxia, in the ventilatory response to hypoxia and in respiratory rhythm
      generation. In the post-genomic period, the hypoxic ventilatory responses of mice
      carrying targeted deletion of genes that affect synthesis or degradation or
      receptor interaction of SP have been examined by us and also by other
      investigators. A brief summary of the findings from these investigations will
      also be presented. The combined observations from the pre- and post-genomic era
      strongly support the involvement of SP and also other tachykinins in the control
      of respiration during hypoxia.

PMID- 12809616
TI  - Neuronal growth factors and development of respiratory control.
AB  - Neurotrophic molecules, released by neurons and neural target tissues, play a
      pivotal role in regulating neuronal development and plasticity. This article
      reviews recent work demonstrating the pivotal role of two such molecules, brain
      derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic
      factor (GDNF), in the growth and maturation of respiratory neurons and the
      expression of normal ventilatory behavior. Although BDNF and GDNF are
      structurally dissimilar and signal through wholly distinct receptors, they are
      both required for development of peripheral chemoafferent neurons that provide
      hypoxic drive to the brainstem respiratory network. Studies of genetically
      engineered mice carrying targeted deletions in the genes encoding BDNF and GDNF,
      as well as genetic linkage analysis in humans, indicate that these trophic
      molecules may be candidate genes for human developmental disorders of breathing.

PMID- 12809617
TI  - Genetic aspects of breathing: on interactions between hypercapnia and hypoxia.
AB  - Indeed, specific genes in humans and mice regulate breathing pattern at baseline
      and breathing control during chemical stimulation. The current review addresses
      the question of coupling plausible candidate genes to physiological variation in
      control of breathing. That is, can genes discovered in mice be candidates
      assigned to similar physiological mechanisms as genetic control of breathing in
      humans? As an illustration, this review examines the interaction of hypoxia in
      affecting the hypercapnic ventilatory sensitivity (HCVS) curve in humans and
      mice. Strain distribution patterns (SDPs) incorporating ten inbred mouse strains
      demonstrate that hypoxic stimulation likely influences HVCS via an additive
      mechanism rather than synergy between hypercapnia and hypoxia (i.e. CO(2)
      potentiation). As a mechanism associated with the chemical control of breathing
      in humans, the absence of CO(2) potentiation in mice suggests that specific genes
      interact to establish variation in complex breathing traits among mouse strains
      and between species. If future studies support the current evidence, the absence
      of CO(2) potentiation in mice compared with humans suggest a clearly defined
      species difference, which may depend on alternative hypoxic interactions such as
      hypometabolic and central neuronal depressive mechanisms in mice. Because the
      complexity of breathing mechanisms varies with modest adjustments in the
      environment, gene-targeting strategies that achieve 'one-gene, one-phenotype'
      results must be complimented with alternative strategies that consider
      integrating complex respiratory mechanisms with gene-to-gene interactions.

PMID- 12809618
TI  - Periodic breathing and genetics.
AB  - The episodic waxing and waning of ventilation is a fundamental event in sleep
      apnea syndromes. Post-hypoxic frequency decline (PHFD) and periodic breathing
      (PB) are evoked by brief hypoxic exposures in unanaesthetized and unrestrained
      inbred C57BL/6J mice, but not in A/J mice; and expression of PHFD differs not
      only among these mice strains but in among rat strains as well. These
      observations along with the current literature on genetic factors that operate on
      ventilatory behavior at rest and with chemosensory drive lead to the hypothesis
      that genetic factors infer some proportion of risk for the ventilatory
      instability observed in human sleep apnea syndromes.

PMID- 12809619
TI  - Genomic approaches to understanding obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is an increasingly recognized, common chronic
      disease in the developed nations and is a complex disease that has high social
      and economic costs. OSA and its associated 'intermediate' phenotypes-craniofacial
      structure, body fat distribution and metabolism, and neurological control of the
      upper airway muscles and of sleep and circadian rhythm-are under a substantial
      degree of genetic control. Investigating the genetic aetiology of OSA offers a
      means of better understanding its pathogenesis, with the goal of improving
      preventive strategies, diagnostic tools and therapies. Molecular studies of OSA
      itself are in their infancy, but considerable effort and expense has already been
      expended in attempts to detect genetic loci contributing to OSA-associated
      intermediate phenotypes, such as obesity. However, many of the fundamental
      questions relating to the genetic epidemiology of OSA and associated factors
      remain unanswered. This chapter reviews the current state of knowledge of the
      genetics of OSA, with a focus on genomic approaches to understanding sleep
      disorders.

PMID- 12809620
TI  - Functional genomics of sleep.
AB  - Functional genomics is a systematic and high-throughput effort to analyze the
      functions of genes and gene products. Functional genomics is divided into gene-
      and phenotype-driven approaches. Gene-driven approaches to the functional
      genomics of sleep have demonstrated that transcripts of many genes change as a
      function of behavioral state. A phenotype-driven approach includes identification
      and characterization of gene function through the analyses of natural polygenic
      traits, creation of transgenic animals or high-throughput mutagenesis.
      Identification of a gene for narcolepsy through QTL analyses and concomitantly
      using a transgenic approach is one example of the phenotype-driven approach to
      the functional genomics of sleep. Though the majority of functional genomics is
      currently performed in mice, the rat is emerging as an important model for
      genomic research. Since rest in Drosophila shares many features with mammalian
      sleep, this allows a comparative functional genomics approach to the study of
      rest and sleep. The concepts outlined here for the functional genomics of sleep
      are applicable to respiration research.

PMID- 12809621
TI  - Understanding the molecular responses to hypoxia using Drosophila as a genetic
      model.
AB  - We have previously discovered that Drosophila melanogaster could recover from
      extended periods of anoxia (0% oxygen) with no apparent consequential injuries.
      We have since employed forward and reverse genetic approaches to decipher the
      molecular basis for anoxia tolerance. In so doing, we have identified several
      independent mutant lines that demonstrated increased sensitivity to anoxia.
      Characterization of one of these mutants resulted in the identification of a
      dADAR gene that plays a role in the sensitivity to low levels of oxygen. We have
      also used microarrays to study all known Drosophila genes, the expression of
      which may be altered by hyoxia. Microarrays experiments have generated a large
      body of information that is being currently analyzed. We believe that these
      undertakings will provide insight into the genetic mechanisms of hypoxia
      tolerance and ischemic injuries.

PMID- 12809622
TI  - Functional genomics and proteomics in control of breathing.
AB  - New genomic and proteomic techniques offer remarkable promise as tools to address
      longstanding questions regarding molecular mechanisms involved in the control of
      breathing. Here, these techniques are described. Additionally, recent examples of
      the application of these and related molecular techniques are provided
      particularly including observations regarding the role of S-nitrosylation
      signaling reactions in regulating ventilatory responses.

PMID- 12809623
TI  - Variation in human ventilatory control-genetic influence on the hypoxic
      ventilatory response.
AB  - Studies in human subjects have shown considerable variation in the ventilatory
      response to hypoxia among individuals. The potential influence of genetic factors
      was initially suggested by the finding of clusters of low responses in families
      of patients with unexplained hypoventilation and endurance athletes. Further
      evidence of a genetic effect was evident in studies which found greater
      similarity of hypoxic ventilatory response in monozygotic than in dizygotic
      twins. The apparently selective effect on the hypoxic versus the hypercapnic
      response suggests that the genetic influence is related to peripheral
      chemosensitivity. Studies in cats and rats also point to a genetic effect on the
      carotid body.

PMID- 12809624
TI  - Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of
      breathing?
AB  - As part of a large scale, high through-put physiologic genomics study, we sought
      to determine whether genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to
      phenotypic differences in the control of breathing between two inbred rat strains
      (SS/Mcw and BN/Mcw). Through a chromosomal substitution breeding strategy, we
      created 5 consomic rat strains (SS.BN9, SS.BN13, SS.BN16, SS.BN18, and SS.BN20),
      which were BN/Mcw homozygous at only one chromosome and SS/Mcw homozygous at all
      other chromosomes. Standard plethsmography was used to assess eupneic breathing
      and ventilatory responses to CO(2) (FI(CO(2))=0.07) and hypoxia (FI(CO(2))=0.12),
      and Pa(CO(2)) during treadmill exercises provided the index of the exercise
      hyperpnea. There were no robust differences in eupneic breathing between any
      strains. The ventilatory response to CO(2) was 150% greater (P<0.001) in the
      SS/Mcw rats than in the BN/Mcw rats and all consomic strains had the SS/Mcw
      phenotype. Hyperventilation during hypoxia did not differ between the parental
      and the consomic strains, but ventilation during hypoxia was greater (P<0.001) in
      the SS/Mcw than in the BN/Mcw, and the SS.BN9, and SS.BN18 appeared to acquire
      this BN/Mcw phenotype. The hyperventilation during treadmill walking was greater
      (P<0.006) in the BN/Mcw and the SS.BN18 rats than in the SS/Mcw rats. Finally,
      the duration of the apnea following an augmented breath (post sigh apnea, PSA)
      was greater (P<0.001) in the BN/Mcw and the SS.BN9 rats than all other strains.
      We conclude that the robust difference between the parental strains in
      ventilatory CO(2) sensitivity is not due to genotypic differences on the 5
      chromosomes studied to date, but genotypic differences on chromosomes 9 and 18
      contribute to differences in ventilatory responses to hypoxia, exercise, and/or
      to the differences in the PSA.

PMID- 12809625
TI  - The relationship of the legalisation of midwifery and safe motherhood.

PMID- 12809626
TI  - The impact of inequality on the health of mothers.
AB  - In this paper presented at a conference in October 2002, the author presents the
      causes of maternal mortality and shows how these are related to inequalities in
      education, finance and access to family planning and health facilities. The
      commitment of the EU to breaking this cycle is outlined.

PMID- 12809627
TI  - Midwifery and the enlarged European Union.
AB  - The freedom of movement of midwives within the European Union has been guaranteed
      by the application of midwives' sectoral directives signed in 1980 and applied in
      1983. Since then the size of the European Union has grown from 9 to 15 members
      and is due for a next wave of enlargement of another 10 member states in 2004.
      The rules and regulations that govern the European Union are being revisited to
      accommodate this change. Midwifery will be affected and some changes are
      potentially worrying, in particular the proposed loss of the Advisory Committee
      on the Training of Midwives. Six other professions regulated in a very similar
      way are also to lose their own advisory committees. The European Commission has
      proposed the adoption of a single directive for all professions, together with
      the setting up of an expert group whose function would be to deal principally
      with health professions. However, neither its remit nor its membership has been
      determined. Whereas previous movement of midwives within Europe has been minimal,
      it is anticipated that this may well be changed at the next enlargement stage.
      Without clear directives and some form of controlling power at European level,
      public health may be threatened. In this paper the developments to date and the
      concerns that have emerged from the recent proposals are outlined.

PMID- 12809628
TI  - Reproductive history and involvement in pregnancy and childbirth of fathers of
      babies born to teenage mothers in Stockholm, Sweden.
AB  - OBJECTIVE: to describe and compare sexual and reproductive history as well as
      reactions to the pregnancy and attendance in antenatal care, family classes and
      childbirth of fathers of babies born to teenage mothers and fathers of babies
      born to average aged mothers. DESIGN: a descriptive comparative study using a
      structured questionnaire for data collection. SETTING: eleven postnatal wards at
      the five obstetric and gynaecological departments in the Stockholm area.
      PARTICIPANTS: 132 fathers of babies born to primiparous teenage mothers (Group A)
      and the same number of fathers of babies born to primiparous women aged between
      25-29 years (Group B) who were present in the postnatal wards. FINDINGS: 43 of
      Group A compared to 17% of the Group B fathers had their first intercourse before
      15 years of age. This early sexual debut was related to other health hazard, such
      as use of illicit drugs and cigarette smoking. The majority of the pregnancies in
      Group A were unplanned but most fathers reacted positively to the pregnancy and
      participated in the antenatal care. In contrast, only half of these fathers
      attended family classes. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: fathers
      of babies born to teenage mothers differed from fathers of babies to older
      mothers regarding reproductive background as well as involvement during
      pregnancy. The findings of this study challenge midwives to organise clinical
      practice in order to meet the specific needs of this group.

PMID- 12809629
TI  - Expectant first-time fathers' experiences of pregnancy.
AB  - OBJECTIVE: to describe first-time-expectant fathers' experiences of pregnancy.
      DESIGN: an inductive method using narrative interview form and qualitative
      content text analysis. The text of the transcripts was coded and categorised.
      SETTINGS AND PARTICIPANTS: seven first-time-expectant fathers living in a
      multicultural industrial town in southern Sweden were interviewed individually
      when their partner was in the 38th to 39th week of pregnancy. MEASUREMENTS AND
      FINDINGS: all the fathers-to-be experienced some psychological, social and/or
      physical change during the pregnancy. The main category, was 'time of
      transition'. Eight categories were found under this. They were: 'feelings of
      unreality, 'insufficiency and inadequacy', 'exclusion', 'reality', 'social
      changes', 'physical changes', 'responsibility, and development'. KEY CONCLUSION:
      the fathers'-to-be special needs for support and encouragement during pregnancy
      may be as important as those of the mothers'-to-be. The caregiver needs to be as
      aware of and sensitive to these needs. However, before any interventions can be
      recommended more research is needed.

PMID- 12809630
TI  - The impact of the establishment of a midwife managed unit on women in a rural
      setting in England.
AB  - OBJECTIVE: to determine what impact the changes from consultant-led care to
      midwife-led care in a local maternity service have had on women using that
      service. DESIGN: case study, data were collected by postal questionnaire, semi
      structured, tape-recorded interviews, observations and scrutiny of records.
      SETTING: a small town in rural England. PARTICIPANTS: all pregnant women eligible
      for a midwife-managed unit (MMU) birth in a small rural town in England.
      FINDINGS: the women using the MMU were satisfied with the care they received and
      the MMU style of care. Women giving birth at the MMU and at home required less
      pain relief and were more likely to have an intact perineum than a similar group
      of women giving birth in hospital. Continuity of carer did not appear to be an
      issue for women as long as they felt supported by a known team of midwives.
      Transfer for complications during the birthing process was a cause for anxiety
      and stress for women and their partners. Women, whilst satisfied with the MMU,
      would prefer the consultant-led maternity hospital to be re-established in the
      town. The home-birth rate rose by 28% when the consultant unit closed.
      IMPLICATIONS FOR PRACTICE: while the establishment of a midwife-managed unit has
      provided increased choice for a minority of women, the removal of the consultant
      unit in the town has disadvantaged the majority of pregnant women. While
      guidelines are needed when establishing these units the application of
      restrictive inclusion and exclusion criteria can sometimes force women to make
      less appropriate birth choices.

PMID- 12809631
TI  - Searching for autonomy.
AB  - OBJECTIVE: to gain an understanding of what midwives understand by the term
      'autonomy',and to discover whether they consider themselves and their colleagues
      to be autonomous in practice. PARTICIPANTS: a snowball sample of 27 midwives
      working in five National Health Service (NHS) trusts within the south west of
      England, based in both hospitals and in the community. METHOD: within a
      qualitative research design, semi-structured interviews with participants were
      tape-recorded and transcribed verbatim, and analysed using thematic content
      analysis. FINDINGS: most participants did not fully understand the implications
      of professional autonomy, particularly in terms of interprofessional
      collaboration and control of their own practice. There were mixed views among
      respondents about whether they practised autonomously. Although good
      relationships with medical personnel were found to facilitate midwifery autonomy,
      the ongoing dominance of the medical profession was still perceived as a major
      barrier to autonomy. Many participants did not feel that their midwifery
      education had equipped them for professional autonomy, although midwives educated
      by the direct-entry route were perceived to be more capable of exercising
      autonomy in practice than were nurse-trained midwives. Some participants
      expressed doubts about the possibility of genuine midwifery autonomy within the
      present system, while others felt that many midwives do not support their own or
      other midwives' professional autonomy. IMPLICATIONS FOR PRACTICE: midwives need
      to initiate major change at a collective level, or to consider the creation of
      obstetric nursing posts, both to afford women the choice of genuinely autonomous
      midwifery care and to alleviate the stresses of practising within a system that
      requires the accountability and responsibility of midwifery autonomy, yet neither
      recognises nor supports it.

PMID- 12809632
TI  - How well do midwives estimate the date of delivery?
AB  - OBJECTIVE: to compare expected date of delivery (EDD) and gestational age (GA)
      obtained by midwives with those calculated using the Confidential Enquiry into
      Stillbirths and Death in Infancy (CESDI) recommended formula. DESIGN:
      retrospective study of obstetric records and prospective study of clinical cases
      examined by multiple midwives. SETTING: postnatal wards, Maternity Unit,
      Plymouth, Devon, UK. PARTICIPANTS: two studies were performed. The first was a
      retrospective analysis of 115 sets of obstetric records. The second, a
      prospective study which included five clinical cases and 19 qualified midwives
      whose experience ranged from six months to 25 years. FINDINGS: in the
      retrospective study, 68 (59%) of the 115 obstetric case notes had sufficient
      information to apply the CESDI formula. The midwives'calculated EDD was
      interpreted to a GA and 35 (52.5%) agreed to within three days of the GA derived
      from the CESDI formula EDD. In the prospective study, the midwives' calculation
      of EDD was in good agreement with the CESDI formula in cases where last menstrual
      period (LMP) was known and menstrual cycle was 28 days with 17 (90%) of the 19
      midwives providing the EDD to within three days of the CESDI formula. In the
      clinical case where LMP was known but menstrual cycle length was 33 days only two
      (10%) of the 19 calculated the EDD within three days of the CESDI formula. KEY
      CONCLUSIONS: when LMP is known and the cycle length is 28 days, midwives produce
      results consistent with the CESDI formula. However, when the menstrual cycle
      differs from 28 days or LMP is unknown, inaccurate or ambiguous and obstetric
      ultrasound scan (USS) information is used to calculate the EDD, the midwives show
      varying degrees of departure from the CESDI formula. Further, we found that the
      midwives tended to produce underestimates when calculating GA from EDD. This bias
      occurs across the range of gestations covered, including early gestations when
      such biases may have more important medical implications. IMPLICATIONS FOR
      PRACTICE: midwives' calculation of EDD and estimation of GA showed both random
      and systematic errors; in some cases, the errors were so large that they may have
      important medical consequences. If the CESDI-recommended formula for calculating
      EDD were used there would be improved accuracy and reliability of EDD and the
      calculation of GA.

PMID- 12809633
TI  - The power of place.
AB  - OBJECTIVE: to describe the power that 'place' holds over the postnatal-care
      experiences of women. DESIGN: a study informed by phenomenology within a feminist
      framework was undertaken to examine the experiences of women electing early
      postnatal discharge. Three extended conversations with each woman participating
      in the study were audiotaped and transcribed. Journal notes made by the
      researcher added to the audiotaped data. Thematic analysis revealed major
      structures of experience. SETTING: data were obtained from conversations with
      women in their respective homes. PARTICIPANTS: five women, parity 1-3, living in
      the Sydney metropolitan area and birthing in their local hospitals participated
      in the study. FINDINGS: four major constructs of experience were revealed through
      analysis and include spatiality, corporeality, temporality and relationality. In
      this paper, components of spatiality expressed through the power place exerts in
      matters of physical environment,control, confidence, safety, time, talk and the
      heart of the matter are presented. KEY CONCLUSIONS: the experiences of women
      entering the foreign place of hospital to birth their children were those of
      alienation and disempowerment while the familiar territory of home offered
      stronger feelings of security and support. IMPLICATIONS FOR PRACTICE: failing to
      recognise the impact of place on the experiences of postnatal women reduces the
      likelihood that midwives will be able to offer sensitive and appropriate care.

PMID- 12809634
TI  - A qualitative study of pregnant teenagers' perceptions of the acceptability of a
      nutritional education intervention.
AB  - OBJECTIVE: in order to assess the feasibility of nutritional education
      intervention sessions for pregnant teenagers, standard dietary assessment
      schedules were supplemented by a qualitative appraisal. Reported in this paper
      are the perceptions of pregnant teenagers who attended one or more of these
      sessions. DESIGN: qualitative study using a phenomenological approach. Data were
      collected using semi-structured tape-recorded group interviews. SETTING: two
      community centres and one maternity unit in Tayside, Scotland. PARTICIPANTS: ten
      pregnant teenagers aged 16-18 years. INTERVENTIONS: all had attended one or more
      of a series of food preparation sessions led by a midwife. Food to take away was
      provided, as were supermarket vouchers. FINDINGS: those who attended found the
      sessions to be social, educational, and practical. These young women appreciated
      being in a group which did not include 'older' pregnant women. To a limited
      extent they had changed their dietary habits at home. Food to take home was a
      significant attraction. Some of the teenagers sought maternity-related
      information from the midwife leading the session. KEY CONCLUSIONS: nutritional
      education remains an important public health issue. Despite offering a range of
      incentives, attracting teenagers to these sessions was difficult, making their
      economic feasibility questionable. IMPLICATIONS FOR PRACTICE: with better
      recruitment, such sessions could form an important part of improving nutrition
      and overall health for current and future generations.

PMID- 12809635
TI  - A systematic review of randomised controlled trials evaluating the effect of
      mother/baby skin-to-skin care on successful breast feeding.
AB  - OBJECTIVE: to examine the effects of early skin-to-skin contact between mother
      and baby on the initiation and duration of breast feeding. REVIEW METHODS: 
      SEARCH STRATEGY: electronic databases--the Cochrane Library, MEDLINE,CINAHL and
      EMBASE. References of studies were examined to identify additional trials and
      contact was made with researchers in the field. Study selection criteria:
      randomised or quasi-randomised controlled trials in any language in which skin-to
      skin contact between mothers and their healthy full-term newborn babies was
      compared to routine contact. Primary outcomes were success of first breast feed
      and duration of breast feeding. Secondary outcomes included, baby temperature and
      behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed
      using criteria defined by the Cochrane Collaboration. Application of inclusion
      criteria, validity assessment and data extraction were carried out independently
      by two reviewers with a third reviewer to resolve differences. FINDINGS: seven
      randomised controlled trials were identified. Five studies assessed duration of
      breast feeding with mixed results. None of the studies assessed the success of
      the first breast-feeding experience. Study quality was variable with methods of
      randomisation and blinding of assessment unclear in four of the five studies
      providing relevant results. CONCLUSIONS: the findings of this systematic review
      fail to support the current initiatives to implement changes in clinical practice
      to include skin-to-skin contact. Methodological flaws within the included studies
      prohibit firm conclusions being reached with regard to the effect of skin-to-skin
      contact on the duration of breast feeding, timing of first breast feed or baby
      physiological factors. The review highlights the need for further primary
      research to assess the effect of skin-to-skin contact on the breast-feeding
      experience.

PMID- 12809636
TI  - Regulation of the mitochondrial ATP-synthase in health and disease.
AB  - In most tissues the mitochondrial ATP-synthase plays a central role by
      synthesizing the bulk of ATP. According to the classical theory of respiratory
      control, flux through this enzyme is solely determined by substrate (ADP)
      concentration while the enzyme has a fixed capacity. However, in different cell
      types such as rat cardiomyocytes and neurons, dog heart, human fibroblasts, and
      skeletal and heart muscle from children, it has been shown that active regulation
      of the mitochondrial ATP-synthase in response to cellular energy demand exists.
      For example, in rat cardiomyocytes the mitochondrial ATP-synthase activity is
      down-regulated in response to anoxia or mitochondrial uncoupling. By this
      mechanism cellular ATP is conserved, as under these conditions the ATP-synthase
      would work in reverse and hydrolyze ATP. When cardiomyocytes are stimulated to
      contract, ATP-synthase activity is up-regulated in line with the increased energy
      demand. Preincubation of the cardiomyocytes with positive inotropic substances
      results in further up-regulation of the ATP-synthase. By blocking calcium
      transport, it has been shown that the up-regulation of the enzyme is calcium
      dependent. On a molecular level, up-regulation is probably mediated by the
      calcium-binding inhibitor protein (CaBI) and down-regulation via the inhibitor
      protein IF(1). The ATP-synthase system is disturbed under several
      pathophysiological conditions. First, mutations can cause a primary defect in the
      mitochondrial ATP-synthase (respiratory chain defect). Furthermore, secondary
      defects of the ATP-synthase occur. In rat models abnormalities of ATP-synthase
      can be detected in different types of cardiomyopathy/heart hypertrophy. The
      changes are reversible in response to treatment of the heart diseases.
      Abnormalities of the ATP-synthase system can be observed in fibroblasts from
      patients with neuronal ceroidlipofuscinoses. Toxic metabolites accumulating in
      methylmalonic acidurias can inhibit ATP-synthase. When neurons are incubated with
      3-OH glutarate - a substance accumulating in glutaric aciduria I-as a model for
      glutaric aciduria I, ATP-synthase activity is compromised. This lack of energy
      may lead to 'slow onset' excitotoxicity and finally cell death. Cells can be
      rescued by adding creatine to the incubation medium. In D-2-hydroxyglutaric
      aciduria, inhibition of the ATP-synthase has been observed.

PMID- 12809637
TI  - Disease-causing mutations in cis with the common arylsulfatase A pseudodeficiency
      allele compound the difficulties in accurately identifying patients and carriers
      of metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder most often
      caused by mutations in the sulfatide sulfatase or arylsulfatase A (ASA) gene.
      This results in the storage of sulfatides in the peripheral and central nervous
      systems as well as in the kidneys. Patients with MLD exhibit a wide range of
      clinical features presenting from the late infantile period to adulthood. Testing
      for this disease is performed on a majority of the patient samples received for
      diagnostic testing in the authors' laboratory. If low ASA activity is measured,
      additional testing is required to confirm the diagnosis due to several factors.
      ASA activity is also low in individuals with multiple sulfatase deficiency and in
      individuals with copies of the so-called pseudodeficiency (Pd) allele. Due to the
      high frequency of the common Pd allele, it is possible for individuals, both with
      and without neurologic disease, to have low ASA activity but not have MLD.
      Unfortunately, the finding of the Pd mutation by molecular analysis does not rule
      out a diagnosis of MLD. In a recent 25 month period, this laboratory diagnosed 52
      patients with MLD, and of these, 13 patients from 10 families had one or two
      copies of the Pd mutation. Sequencing of the ASA gene in these 10 families
      revealed four new mutations in cis with the Pd allele (S43R, R84Q, R311X, and
      E329R) and two additional new mutations (R299W, C488R). Six patients had
      previously reported mutations on the Pd background. Thus, a total of 14 mutations
      have been found to occur in cis with the Pd allele. We estimate that 1-2% of Pd
      alleles will have a disease-causing mutation, and this complicates the
      identification of patients and the assignment of risk for a couple when a copy of
      the Pd allele is detected.

PMID- 12809638
TI  - Spectrum of mutations in the arylsulfatase A gene in a Canadian DNA collection
      including two novel frameshift mutations, a new missense mutation (C488R) and an
      MLD mutation (R84Q) in cis with a pseudodeficiency allele.
AB  - We describe three novel mutations in the human arylsulfatase A gene in three
      patients with MLD, an autosomal recessive lysosomal storage disorder. An
      insertion, 2590_2591insCCCC in exon 8 and a deletion, 752_758delGCCGGCC, in exon
      3 will both result in frameshifts. A mutation in exon 8, 2566T-->C, results in a
      missense mutation C488R, disrupting an unusual cysteine-knot at the C-terminal
      end of the protein. All three mutations are heterozygous with previously
      documented mutations. A previously reported mutation, R84Q was identified on a
      pseudodeficiency allele. These mutations are part of a heterogeneous spectrum of
      mutations found in a collection of DNA samples from MLD patients from across
      Canada and the USA.

PMID- 12809639
TI  - Mutation analysis of feline Niemann-Pick C1 disease.
AB  - Niemann-Pick C (NPC) disease is an autosomal recessive neurovisceral lysosomal
      storage disorder that results in defective intracellular transport of
      cholesterol. The major form of human NPC (NPC1) has been mapped to chromosome 18,
      the NPC1 gene (NPC1) has been sequenced and several mutations have been
      identified in NPC1 patients. A feline model of NPC has been characterized and is
      phenotypically, morphologically, and biochemically similar to human NPC1.
      Complementation studies using cultured fibroblasts from NPC affected cats and
      NPC1 affected humans support that the gene responsible for the NPC phenotype in
      this colony of cats is orthologous to human NPC1. Using human-based PCR primers,
      initial fragments of the feline NPC cDNA were amplified and sequenced. From these
      sequences, feline-specific PCR primers were generated and designed to amplify six
      overlapping bands that span the entire feline NPC1 open reading frame. A single
      base substitution (2864G-C) was identified in NPC1 affected cats. Obligate
      carriers are heterozygous at the same allele and a PCR-based assay was developed
      to identify the geneotype of all cats in the colony. The mutation results in an
      amino acid change from cysteine to serine (C955S). Several of the mutations
      identified in people occur in the same region. Marked similarity exists between
      the human and feline NPC1 cDNA sequences, and is greater than that between the
      human and murine NPC1 sequences. The human cDNA sequence predicts a 1278aa
      protein with a lysosomal targeting sequence, several trans-membrane domains and
      extensive homology with other known mediators of cholesterol homeostasis.

PMID- 12809640
TI  - Gaucher disease with parkinsonian manifestations: does glucocerebrosidase
      deficiency contribute to a vulnerability to parkinsonism?
AB  - Among the phenotypes associated with Gaucher disease, the deficiency of
      glucocerebrosidase, are rare patients with early onset, treatment-refractory
      parkinsonism. Sequencing of glucocerebrosidase in 17 such patients revealed 12
      different genotypes. Fourteen patients had the common "non-neuronopathic" N370S
      mutation, including five N370S homozygotes. While brain glucosylsphingosine
      levels were not elevated, Lewy bodies were seen in the four brains available for
      study. The shared clinical and neuropathologic findings in this subgroup suggest
      that the deficiency in glucocerebrosidase may contribute to a vulnerability to
      parkinsonism.

PMID- 12809641
TI  - Large neutral amino acid therapy and phenylketonuria: a promising approach to
      treatment.
AB  - Six subjects with classical phenylketonuria (PKU) were treated with large neutral
      amino acid supplements (PreKUnil, Nilab, Dk) at 0.4g/kg/day in equally divided
      doses three times each day on an increased natural protein diet. All six subjects
      had low or deficient blood concentrations of both tyrosine and tryptophan, which
      are precursors for dopamine and serotonin, respectively, at the beginning of the
      study and were increased substantially throughout the study. Blood phenylalanine
      concentrations remained essentially unchanged, while the brain phenylalanine
      concentrations gradually decreased toward the carrier range as seen in parents of
      children with PKU. Two subjects were diagnosed with clinical depression and were
      in counseling programs at initiation of the study. At the end of the study all
      patients reported increased energy and overall improvement in well-being.

PMID- 12809642
TI  - Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
AB  - Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or
      trifunctional protein (TFP) deficiency consists of fasting avoidance, and
      limiting long-chain fatty acid (LCFA) intake. This study reports the relationship
      of dietary intake and metabolic control as measured by plasma acylcarnitine and
      organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1
      year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11%
      as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of
      hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters
      positively correlated with total LCFA intake and negatively correlated with MCT
      intake suggesting that as dietary intake of LCFA decreases and MCT intake
      increases, there is a corresponding decrease in plasma hydroxyacylcarnitines.
      There was no correlation between plasma acylcarnitines and level of carnitine
      supplementation. Dietary intake of fat-soluble vitamins E and K was deficient.
      Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic
      acid, were deficient. On this dietary regimen, the majority of subjects were
      healthy with no episodes of metabolic decompensation. Our data suggest that an
      LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate
      protein and limited LCFA intake (10% of total energy) while providing 10-20% of
      energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that
      includes all of the fat-soluble vitamins. The diet should be supplemented with
      vegetable oils as part of the 10% total LCFA intake to provide essential fatty
      acids.

PMID- 12809643
TI  - A splice junction mutation in muscle carnitine palmitoyltransferase II
      deficiency.
AB  - We report the first splice junction mutation to be described in the carnitine
      palmitoyltransferase (CPT) 2 gene in a patient with the muscle form of CPT II
      deficiency. The patient, a 25-year-old man, suffered from attacks of myalgia and
      muscle weakness in early adult life. There was biochemical evidence of CPT II
      deficiency. Molecular genetic analysis revealed the common S113L mutation on one
      allele whilst a novel mutation at the splice donor junction in intron 3 was
      identified on the other allele. Sequencing of reverse transcription polymerase
      chain reaction (RT-PCR) products clearly demonstrated that this mutation causes
      the skipping of exon 3, thus establishing its pathogenic role.

PMID- 12809644
TI  - Analysis of the human folate receptor beta gene for an association with neural
      tube defects.
AB  - The folate receptor beta (FRbeta) gene encodes a receptor that binds and
      transports 5-methyltetrahydrofolate. FRbeta polymorphisms may potentially alter
      folate delivery and are likely candidates for an association with neural tube
      defect (NTD) risk. To look for association between FRbeta polymorphisms we
      studied NTD-affected children and their parents (254 triads) recruited throughout
      Ireland and a control population of 296 pregnant women who did not give birth to
      an NTD-affected child. Five potential single nucleotide polymorphisms (SNPs) were
      examined. These were located within the coding, intronic and 3(')-untranslated
      regions of the FRbeta gene. Four of these SNPs were not found to be variable
      within our Irish cohort. SNP rs651646 (A-->T), located upstream of exon 2 within
      an intronic region, is polymorphic and is thus a marker for an FRbeta NTD
      association study. The frequency of the SNP rs651646 "A" allele was not
      significantly different in cases (odds ratio [OR] 1.07, 95% CI. 0.84-1.36;
      P=0.60), their mothers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.51) or
      fathers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.50) when compared to
      controls. Comparisons of allele transmission from 255 informative heterozygous
      parents of NTD cases showed no preferential transmission of either the A or T
      alleles (A: 50.2%, n=128; T: 49.8%, n=127; P=1.00, McNemar chi(2) 0.0). We also
      measured allele frequencies in a sample of American-Caucasians and African
      Americans. Highly significant allele frequency differences were observed between
      populations. In conclusion, SNP rs651646 within the FRbeta gene is polymorphic
      but is not associated with neural tube defects within the Irish population.

PMID- 12809645
TI  - Refinement of the Smith-Magenis syndrome critical region to approximately 950kb
      and assessment of 17p11.2 deletions. Are all deletions created equally?
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental
      retardation syndrome associated with an interstitial deletion of chromosome
      17p11.2. SMS is thought to be a contiguous gene syndrome caused by
      haploinsufficiency of one or more genes in the associated deletion region. To
      date, no gene has been reported to contribute to the characteristics seen in the
      SMS phenotype. To expedite the search for the SMS causative genes, we have
      reduced the SMS critical region to approximately 950kb by analyzing 11 patient
      samples carrying 17p11.2 deletions. In addition, we have re-evaluated the
      frequency with which different 17p11.2 deletions naturally occur, showing
      evidence that homologous recombination likely takes place between low copy
      repeats at a higher frequency than previously reported.

PMID- 12809646
TI  - A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with
      hepatic glycogen storage disease and residual enzyme activity.
AB  - We identified a novel mutation in the glycogen phosphorylase gene (PGYL) in a
      Chinese patient with glycogen storage disease (GSD) type VI. The patient
      presented with gross hepatomegaly since the age of two without history of any
      hypoglycemic attack. Otherwise, he was largely asymptomatic. Liver tissue enzyme
      assays revealed a mild deficiency of total glycogen phosphorylase. Both PGYL and
      PHKA2 genes were sequenced. The patient was homozygous of a missense mutation
      G233D in PGYL. This location forms a hairpin turn secondary structure and the
      small glycine residue is completely conserved in all the orthologous proteins
      from Escherichia coli to mammals. This is the sixth reported mutation of this
      form of GSD.

PMID- 12809647
TI  - A genetic study of cathepsin C gene in two families with Papillon-Lefevre
      syndrome.
AB  - Papillon-Lefevre syndrome (PLS) is an inherited human disorder characterised by
      premature destruction of the periodontium of the deciduous and permanent teeth,
      palmoplantar hyperkeratosis, and increased susceptibility to bacterial infections
      during the first years of life. In this paper two PLS families have been studied.
      Family 1 presents a novel homozygous mutation (880T>C) in exon 6 causing Y294H
      amino acid substitution. Family 2 shows a previously described non-sense
      homozygous punctual change (72C>A) that introduces a termination codon at the
      extracellular domain of the protein (C24X).

PMID- 12809648
TI  - Update on tetraplegia.

PMID- 12809649
TI  - Recording congenital differences of the upper limb.
AB  - Consistent classification of congenital differences of the upper limb is of
      paramount importance for the study of the pathogenesis. To overcome the
      inconsistencies of present classifications, a non-classifying recording method
      has been developed. This method records individual aberrations, including bone
      and soft-tissue defects. Between 1996 and 1998, a prospective study was performed
      to validate the method. Two hundred and thirty-one patients with upper limb
      differences were assessed, and all individual aberrations were recorded. These
      data can be transferred to any classification. It is concluded that the presented
      method will allow consistent grouping of patients without losing details about
      simple and complex differences.

PMID- 12809650
TI  - The classification of phocomelia.
AB  - We studied 24 patients with 44 phocomelic upper limbs. Only 11 limbs could be
      grouped in the classification system of Frantz and O' Rahilly. The non
      classifiable limbs were further studied and their characteristics identified. It
      is confirmed that phocomelia is not an intercalary defect.

PMID- 12809651
TI  - Compression and stretching of the brachial plexus in thoracic outlet syndrome:
      correlation between neuroradiographic findings and symptoms and signs produced by
      provocation manoeuvres.
AB  - In order to investigate the mechanism of nerve irritation in thoracic outlet
      syndrome (TOS), we studied 150 patients who presented with symptoms of neurologic
      TOS between 1985 and 1999. They first performed various provocative physical
      manoeuvres and then underwent injection of contrast medium into the
      supraclavicular part of the brachial plexus. Several of the provocative
      manoeuvres were then repeated and radiographs were again obtained. Based on the
      neuroradiographs, we identified three subsets of patients; those with only
      compression (type 1 TOS, n=27, 18%), those with combined compression and
      stretching (type 2 TOS, n=111, 74%), and those with only stretching (type 3 TOS,
      n=12, 8%). We were able to correlate the neuroradiological subsets with symptoms
      elicited by pre-radiographic provocative manoeuvres; in 92 patients (61%) these
      were elicited by traction manoeuvres. We conclude that stretching is an important
      factor of nerve irritation in TOS.

PMID- 12809652
TI  - Dynamic splinting after extensor tendon repair in zones V to VII.
AB  - This retrospective study evaluates a dynamic active motion protocol for extensor
      tendon repairs in zones V to VII. Fifty-eight patients with 87 extensor tendon
      injuries were examined. Using Geldmacher's and Kleinert and Verdan's evaluation
      systems, the results were graded as "excellent" and "good" in more than 94%, and
      as "satisfactory" in the remainder. The need for secondary tenolysis was low
      (6%), and no other surgical complication occurred.

PMID- 12809653
TI  - External fixation for surgical treatment of a mallet finger.
AB  - A new surgical technique is described for the treatment of mallet finger
      deformity which involves the application of a mini external fixator across the
      distal interphalangeal joint and resection of a portion of the extensor
      mechanism. We reviewed 19 patients who were treated with this technique, at a
      mean follow-up period of 36 (range, 24-48) months. The mean extensor lag was 2
      degrees (range, -7 degrees to 13 degrees ) and the mean flexion range was 70
      degrees (range, 20 degrees -90 degrees ).

PMID- 12809654
TI  - No more frayed ends--a technique for trimming the uneven ends of ruptured flexor
      tendons prior to repair.
AB  - We describe a technique for the accurate and conservative debridement of the ends
      of divided flexor tendons. We have found this technique particularly useful for
      the secondary repair of tendons after re-rupture.

PMID- 12809655
TI  - A modification in technique of abductor digiti minimi (Huber) opponensplasty.
AB  - Abductor digiti minimi opponensplasty is a well-established method of restoring
      opposition following median nerve trauma or in congenital deficiency of thenar
      intrinsic musculature. The abductor digiti minimi is detached distally and
      rerouted through a subcutaneous tunnel for insertion into the area of the thumb
      metacarpophalangeal joint. The pivot point for this rotation is the pisiform bone
      and it is at this site that the ulnar nerve is vulnerable to compression by the
      transferred muscle. We describe a modification of technique which involves
      complete islanding of the muscle without re-insertion of its proximal end. This
      eliminates the possibility of this complication without detracting from the
      efficacy of opposition produced by the transferred muscle.

PMID- 12809656
TI  - A new clinical severity scoring system for reflex sympathetic dystrophy of the
      upper limb.
AB  - A scoring system for the clinical severity of reflex sympathetic dystrophy (RSD)
      is proposed. The following signs and symptoms were considered to be significant:
      pain, reduction of finger flexion, swelling, temperature changes, discolouration,
      sensory disturbances, shoulder pain and loss of movement, increased sweating, and
      hair/nail growth changes. One point was assigned for strong expression of most of
      these features, half a point for moderate expression and no point if the feature
      was absent. A total score of 4 points was assumed, empirically, to indicate a
      mild degree of RSD, and the maximum score of 10 to indicate the most severe form
      of RSD. One hundred and forty-six patients with RSD of the hand were classified
      according to this system. Seventy-four patients (51%) had a score of 4-6, 51
      patients (35%) a score of 6.5-8, and 21 patients (14%) a score of 8.5-10. Use of
      this system will allow more precise analysis of RSD patients and facilitate
      comparisons between studies.

PMID- 12809657
TI  - Excision of the trapezium and interposition arthroplasty with gelfoam for the
      treatment of trapeziometacarpal osteoarthritis.
AB  - Excision of the trapezium with Gelfoam interposition was performed in 35 thumbs,
      34 of which were evaluated after an average 5 years. Twenty-four patients had
      unilateral procedures. The follow-up examination included a standardized
      questionnaire and clinical and radiological examinations. Pain relief was
      achieved in all cases. The patients considered that 32 of their operated hands
      had improved function, while two had not improved. All patients were satisfied
      with the final postoperative result. Adduction of the thumb to the index finger,
      and opposition to the tip of the little finger was possible in all cases.
      Weakness, in comparison to the other thumb, of lateral pinch (71%; P=0.0001), tip
      pinch (74%; P=0.007), and grip strength (85%; P=0.006) were observed. The first
      web span was preserved in all hands. Calculation of the trapezial space ratio
      demonstrated only slight, insignificant shortening (7%; P=0.06) of the thumb ray.
      No significant correlations between the postoperative trapezial space ratio and
      lateral pinch strength, tip pinch strength, and grip strength were observed. We
      conclude that excision of the trapezium and Gelfoam interposition has no specific
      complications and is a reliable surgical treatment for osteoarthritis of the
      trapeziometacarpal joint.

PMID- 12809658
TI  - Trapeziometacarpal joint osteoarthritis and carpal tunnel syndrome: a new
      surgical approach for concomitant treatment.
AB  - A new approach for the concomitant surgical treatment of trapeziometacarpal joint
      osteoarthritis and carpal tunnel syndrome through the same incision is described.
      The technique was used in 25 patients (20 women, five men; mean age, 56 years).
      At a mean follow-up of 27 months, there was complete disappearance of the
      symptoms of carpal tunnel syndrome in 20 of the 25 patients, incomplete but
      substantial relief in four patients, and no improvement in one patient. One
      patient had scar tenderness and another had a superficial wound infection. The
      surgical technique is simple, safe and cost-effective as it avoids separate
      operations for both pathologies. The procedure is not suitable for severe carpal
      tunnel syndrome or when direct visualization of the median nerve and the carpal
      tunnel is necessary.

PMID- 12809659
TI  - Evaluation of carpal tunnel release using the Knifelight instrument.
AB  - We have performed a prospective randomized controlled trial to compare the
      results of open carpal tunnel release with those of carpal tunnel release using a
      Knifelight (Stryker, Kalamazoo, MI). This is a new knife with its own battery
      powered light source which enables the operation to be performed through a small
      incision in the palm of the hand. There were 43 patients in the open operation
      group and 39 in the Knifelight group. We found no difference in discomfort
      reported during surgery, in the operative time, in the grip strength measured at
      2 and 6 weeks post-operatively or in the proportion of patients cured of their
      pre-operative symptoms. Patients in the Knifelight group had a statistically
      significant improvement in the time to return to work and in scar tenderness at 6
      weeks post-operatively.

PMID- 12809660
TI  - A study of the relative responsiveness of five sensibility tests for assessment
      of recovery after median nerve injury and repair.
AB  - A longitudinal dynamic cohort study was conducted on patients with median nerve
      injuries to evaluate the relative responsiveness of five sensibility tests: touch
      threshold using the WEST (monofilaments), static two-point discrimination,
      locognosia, a pick-up test and an object recognition test. Repeated assessments
      were performed starting at 6 months after surgery. In order to compare the
      relative responsiveness of each test, effect size and the standard response mean
      were calculated for sensibility changes occurring between 6 and 18 months after
      repair. Large effect sizes (>0.8) and standard response means (>0.8) were
      obtained for the WEST, locognosia, pick-up and object recognition tests. Two
      point discrimination was hardly measurable at any time point and exhibited strong
      flooring effects. Further analysis of all time points was undertaken to assess
      the strength of the monotonic relationship between test scores and time elapsed
      since surgery. Comparison of monotonicity between the five tests indicated that
      the WEST performed best, whereas two-point discrimination performed worst. These
      results suggest that the monofilament test (WEST), locognosia test, Moberg pick
      up test and tactile gnosis test capture sensibility changes over time well and
      should be considered for inclusion in the outcome assessment of patients with
      median nerve injury.

PMID- 12809661
TI  - The position of the centre of the distal radial articular surface in the sagittal
      plane: a radiological study.
AB  - Using a digital vernier calliper, measurements of the position of the centre of
      the distal radial articular surface in the sagittal plane with respect to the
      long axis of the distal radius were made on 50 lateral radiographs of normal
      wrists. In all 50 cases, the centre of the distal radial articular surface was
      palmar on the long axis of the radius. The mean value for this palmar position
      was 5.3mm (44% of the radial shaft width). There was no correlation between the
      position of the centre of the distal radial articular surface and either the
      width of the radial shaft, the length of the articular surface of the distal
      radius or the age or sex of the individuals. However, the position of the centre
      of rotation was found to correlate with palmar tilt. The palmar position of the
      centre of the distal radial articular surface on the long axis of the radius may
      be biomechanically important.

PMID- 12809662
TI  - Palmar plate fixation of AO type C2 fracture of distal radius using a locking
      compression plate--a biomechanical study in a cadaveric model.
AB  - The stability of palmar plate fixation using a locking compression T-plate was
      compared with that of a conventional palmar T-plate and a dorsal T-plate in a
      cadaveric model of an AO type C2 fracture of distal radius. The wrist axial load
      transmission through the radius was tested for each fixation. The results show
      that, under 100N axial load, the palmar locking compression T-plate restores
      stability comparable to that of the intact radius, and is superior to
      conventional palmar or dorsal T-plates.

PMID- 12809663
TI  - Reconstruction of the interosseous ligament of the forearm reduces load on the
      radial head in cadavers.
AB  - Excision of the radial head after fracture may be complicated by longitudinal
      radio-ulnar instability (Essex-Lopresti lesion) if the forearm interosseous
      ligament has also been torn. In such cases proximal migration of the radius
      occurs, and ulnar impaction at the wrist and radiocapitellar contact at the elbow
      may impair function. Although metal radial head arthroplasties are now used for
      irreparable radial head fractures, the long-term clinical outcome may still be
      unsatisfactory because of excessive radiocapitellar load causing pain.
      Interosseous ligament reconstruction might improve outcome by restoring normal
      load transfer from the radius to ulna, but the biomechanical effect of
      reconstruction has not been reported. This study evaluated forearm load transfer
      following interosseous ligament reconstruction with an Achilles tendon allograft
      in a cadaveric model with the radial head intact. Interosseous ligament
      reconstruction reduced proximal radius loading by transferring force to the
      proximal ulna, but force transfer by the reconstruction was only half that by the
      intact ligament.

PMID- 12809664
TI  - Salvage of failed Sauve-Kapandji procedure with an ulnar head prosthesis: report
      of three cases.
AB  - Three failed Sauve-Kapandji procedures were salvaged using an ulnar head
      prosthesis. At 7-22 month follow-up, all three patients were much improved.
      However, the stem of one implant subsequently fractured in a fall and this
      implant had to be removed.

PMID- 12809665
TI  - Perioperative complications associated with brachial plexus repair in infants.
AB  - This report details the complications experienced during 100 consecutive cases of
      brachial plexus surgery in infants. There were eight perioperative complications.
      There was no mortality or permanent sequelae from any complication.

PMID- 12809666
TI  - Congenital duplication of the palm in a patient with multiple anomalies.
AB  - In 1995, Parr and McMahon described a syndrome of congenital duplication of
      footpads in mice which lacked a protein called 'Wingless-type mouse mammary
      tumour virus integration site family member 7a" (Wnt-7a). This syndrome has not
      been described in humans and the following report describes a similar syndrome in
      a Saudi girl. The role of Wnt-7a in the development of the limb along the dorso
      ventral axis is discussed, along with interaction between the Wnt-7a and other
      axes of limb growth.

PMID- 12809669
TI  - Re: Clinical value of electrodiagnostic testing following repair of peripheral
      nerve lesions: a prospective study. Th. H.J. Van de Kar, J.B. Jaquet, J.
      Meulstee, C.B.H. Molenaar, R.J. Schimsheimer, S.E.R. Hovius. Journal of Hand
      Surgery, 2002; 27B(4): 345-349.

PMID- 12809671
TI  - CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and
      obsessive compulsive disorder.
AB  - Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex
      neuropsychiatric disorder characterized by involuntary motor and vocal tics.
      There is comorbidity with disorders like obsessive compulsive disorder and
      attention deficit hyperactivity disorder. Until now linkage analysis has pointed
      to a number of chromosomal locations, but has failed to identify a clear
      candidate gene(s). We have investigated a GTS family with a complex chromosomal
      insertion/translocation involving chromosomes 2 and 7. The affected father
      [46,XY,inv(2) (p23q22),ins(7;2) (q35-q36;p21p23)] and two affected children
      [46,XX,der(7)ins(7;2)(q35-q36;p21p23) and 46,XY,der(7)ins(7;2)(q35-q36;p213p23)]
      share a chromosome 2p21-p23 insertion on chromosome 7q35-q36, thereby
      interrupting the contactin-associated protein 2 gene (CNTNAP2). This gene encodes
      a membrane protein located in a specific compartment at the nodes of Ranvier of
      axons. We hypothesize that disruption or decreased expression of CNTNAP2 could
      lead to a disturbed distribution of the K(+) channels in the nervous system,
      thereby influencing conduction and/or repolarization of action potentials,
      causing unwanted actions or movements in GTS.

PMID- 12809672
TI  - An exhaustive DNA micro-satellite map of the human genome using high performance
      computing.
AB  - The current pace of the generation of sequence data requires the development of
      software tools that can rapidly provide full annotation of the data. We have
      developed a new method for rapid sequence comparison using the exact match
      algorithm without repeat masking. As a demonstration, we have identified all
      perfect simple tandem repeats (STR) within the draft sequence of the human
      genome. The STR elements (chromosome, position, length and repeat subunit) have
      been placed into a relational database. Repeat flanking sequence is also publicly
      accessible at http://grid.abcc.ncifcrf.gov. To illustrate the utility of this
      complete set of STR elements, we documented the increased density of potentially
      polymorphic markers throughout the genome. The new STR markers may be useful in
      disease association studies because so many STR elements manifest multiallelic
      polymorphism. Also, because triplet repeat expansions are important for human
      disease etiology, we identified trinucleotide repeats that exist within exons of
      known genes. This resulted in a list that includes all 14 genes known to undergo
      polynucleotide expansion, and 48 additional candidates. Several of these are non
      polyglutamine triplet repeats. Other examinations of the STR database
      demonstrated repeats spanning splice junctions and identified SNPs within repeat
      elements.

PMID- 12809673
TI  - Linkage disequilibrium analysis of the human adenosine deaminase (ada) gene
      provides evidence for a lack of correlation between hot spots of equal and
      unequal homologous recombination.
AB  - The linkage disequilibrium (LD) pattern within the adenosine deaminase (ADA) gene
      was analyzed by studying 13 polymorphic loci in 137 families from two European
      and three African populations. Evidence for the presence of a 12-kb meiotic
      crossover hot spot, spanning part of the first and the second intron and flanked
      by regions of reduced recombination activity, was obtained. Moreover, segregation
      analysis of 113 informative meioses revealed two recombination events that are
      internal or overlap the 12-kb region, thus suggesting a recombination rate for
      the hot-spot region about 50-fold higher than the mean rate across the human
      genome. Within the hot spot, a 144-bp palindromic sequence was also identified
      and its possible involvement in the recombination process is discussed. The 12-kb
      region characterized by the low degree of LD does not include the 3.2-kb region
      that is deleted, as a result of recurrent unequal homologous recombination
      between two Alu elements, in patients affected by autosomal severe combined
      immunodeficiency. This observation provides the first evidence for an absence of
      correlation between hot spots of equal and unequal homologous recombination.

PMID- 12809674
TI  - The mouse Ifi200 gene cluster: genomic sequence, analysis, and comparison with
      the human HIN-200 gene cluster.
AB  - The interferon-activatable Ifi200 gene cluster is located on mouse Chromosome
      1q21-q23. We report here our analysis of two genomic regions encoding at least 10
      closely related 200 family genes (Ifi201, Ifi202a, Ifi202b, Ifi202c, Ifi203a,
      Ifi203b, Ifi203c, Ifi203', Ifi204, and Ifi204') in 129/SvJ mice. Through a BAC
      based sequencing approach, the exact structure and organization of these highly
      similar Ifi200 genes were obtained. A high degree of conservation (99% identity)
      was observed between Ifi202a and b and between Ifi203a and b. The presence of an
      additional transcribed region in intron 4 of Ifi203a and b suggests the
      possibility of alternative splicing, and a spliced variant of the Ifi204' mRNA
      exhibits 91% sequence identity with a related but unmapped D3 mRNA. Comparative
      analysis of the mouse and human clusters indicates an absence of significant
      sequence conservation in noncoding sequences, suggesting that the 200 family
      emerged prior to human-mouse speciation and subsequently diverged after gene
      duplication.

PMID- 12809675
TI  - A cluster of proton/amino acid transporter genes in the human and mouse genomes.
AB  - We recently cloned and functionally characterized two novel proton/amino acid
      transporters (PAT1 and PAT2) from mouse. Here we report the isolation of the
      corresponding cDNAs of the human orthologues and one additional mouse and human
      PAT-like transporter cDNA, designated PAT3. The PAT proteins comprise 470 to 483
      amino acids. The mouse PAT3 mRNA is expressed in testis of adult mice. In the
      human and mouse genomes the genes of the PAT transporters (designated SLC36A1-3
      and Slc36a1-3, respectively) are clustered on human chromosome 5q33.1 and in the
      syntenic region of mouse chromosome 11B1.3. PAT-like transporter genes are
      present as well in the genomes of other eukaryotic organisms such as Drosophila
      melanogaster and Caenorhabditis elegans. For the PAT3 subtype transporter, we
      could not yet identify its function. The human PAT1 and PAT2 transporters when
      functionally expressed in Xenopus laevis oocytes show characteristics similar to
      those of their mouse counterparts.

PMID- 12809676
TI  - Genomic structure and promoter analysis of PKC-delta.
AB  - Protein kinase C-delta (PKC-delta) is a ubiquitously expressed kinase involved in
      a variety of cellular signaling pathways including cell growth, differentiation,
      apoptosis, tumor promotion, and carcinogenesis. While signaling pathways
      downstream of PKC-delta are well studied, the regulation of the gene has not been
      extensively analyzed. A mouse genomic DNA fragment containing the PKC-delta gene
      was sequenced by the primer-walking method, and the subsequent DNA sequence data
      were used as a query to clone Caenorhabditis elegans and human genomic homologs
      from the publicly available genomic databases. The genomic structures of C.
      elegans, mouse, rat, and human PKC-delta were analyzed, and the result revealed
      that PKC-delta genes comprise 12, 18, 19, and 18 exons for C. elegans, mouse,
      rat, and human, respectively. The translation start methionine resides in the
      second exon in mouse and human and in the third exon in rat. The first intron
      between the first exon and the exon with the translation start methionine in
      mammalian genes represents a very large gap, as long as 17 kb in human,
      indicating a complexity involved in gene splicing. Overall exon-intron genomic
      structure is highly conserved among mammals, while significantly diverged in C.
      elegans. Putative transcription factor binding sites on the 1.7-kb promoter
      region of the mouse gene suggest that PKC-delta might be involved in
      spermatogenesis, embryogenesis, development, brain generation, immune response,
      oxidative environment, and oncogenesis. Studies on the promoter and subsequent
      biological testing on mouse keratinocytes indicate that tumor necrosis factor
      (TNF)-alpha increases the expression of PKC-delta, and this correlates with the
      time of NFkappaB nuclear translocation and activation. This TNF-alpha-mediated
      upregulation of PKC-delta is repressed in keratinocytes that are preinfected with
      IkappaB superrepressor adenovirus, suggesting that NFkappaB is involved directly
      in PKC-delta expression.

PMID- 12809678
TI  - Analysis of gene expression profiles of gastric normal and cancer tissues by
      SAGE.
AB  - In an attempt to understand the molecular bases of gastric cancer progression, we
      have analyzed the differentially expressed genes in gastric cancer by SAGE. Four
      SAGE cDNA tag libraries were constructed from two sets of gastric cancer and
      normal tissues and 241,127 tags were obtained. By comparing the tags from cancer
      and normal tissues, 414 differentially expressed tags, representing 383 genes,
      were identified in cancer tissues (p </= 0.01). Of the 414 tags, 50 tags were
      previously unidentified and potentially novel genes. Although each gastric cancer
      tissue revealed more than 200 differentially expressed genes compared to the
      respective normal tissue, the number of genes with consistent regulation patterns
      in both cancer tissues was 51: 12 up-regulated and 39 down-regulated genes. The
      genes that showed consistent regulation patterns included well-known genes such
      as Trefoil factor 3, RegIV, gastric intrinsic factor, and lactotransferrin as
      well as a few novel candidates. Interestingly, the expression of several genes,
      such as osteoglycin, prostate stem cell antigen, and histone deacetylase 3, was
      variable in the two normal tissues but similar in the cancer tissues. The
      expression profiles of these genes in normal tissues, possibly due to genetic
      background, could greatly affect individual sensitivity to cancer development
      and/or progression. The genes identified in this study will provide useful target
      genes for diagnosis and molecular treatment of gastric cancer.

PMID- 12809677
TI  - Targeted modification of a human beta-globin locus BAC clone using GET
      Recombination and an I-Scei counterselection cassette.
AB  - There is a need for better approaches to allow precise engineering of large
      genomic BAC DNA fragments, to facilitate the use of intact genomic loci for
      therapeutic and biotechnology applications. We report an efficient method to
      insert any modification in any genomic locus, using a human beta-globin locus BAC
      clone as a model system. The modifications can range from single base changes to
      large insertions or deletions and leave no operational sequences. A
      counterselection cassette, consisting of an inducible I-SceI gene, its
      recognition site, and an antibiotic resistance gene, is inserted into the
      targeted region using GET Recombination. A PCR fragment carrying the modification
      but no selectable marker replaces the counterselection cassette in a second round
      of GET Recombination. The unique I-SceI site in the counterselection cassette is
      cut by I-SceI endonuclease, strongly selecting against nonrecombinant clones and
      yielding up to 30% correct recombinants.

PMID- 12809679
TI  - Linkage mapping of the primary disease locus for collie eye anomaly.
AB  - Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of
      the choroid and sclera segregating in several breeds of dog, including rough,
      smooth, and Border collies and Australian shepherds. The disease is reminiscent
      of the choroidal hypoplasia phenotype observed in humans in conjunction with
      craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can
      vary significantly; many dogs exhibit no obvious clinical consequences and retain
      apparently normal vision throughout life, while severely affected animals develop
      secondary retinal detachment, intraocular hemorrhage, and blindness. We report
      genetic studies establishing that the primary cea phenotype, choroidal
      hypoplasia, segregates as an autosomal recessive trait with nearly 100%
      penetrance. We further report linkage mapping of the primary cea locus to a 3.9
      cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region
      corresponding to human chromosome 2q35. These results suggest the presence of a
      developmental regulatory gene important in ocular embryogenesis, with potential
      implications for other disorders of ocular vascularization.

PMID- 12809680
TI  - Task-switching and long-term priming: role of episodic stimulus-task bindings in
      task-shift costs.
AB  - When subjects switch between two tasks, performance is slower after a task switch
      than after a task repetition. We report five experiments showing that a large
      part of these "task-shift-costs" cannot be attributed to a control operation,
      needed to configure the cognitive system for the upcoming task (e.g., ). In all
      experiments subjects switched between picture-naming and word-reading. We
      presented different stimuli either in just one of the two tasks, or in both of
      them. Shift-costs were larger for stimuli presented in both tasks than for those
      presented in only one task, even after more than 100 intervening trials between
      prime and probe events. We suggest (as proposed by ) that stimuli acquire
      associations with the tasks in which they occur. When the current task activation
      is weak, as on a switch of tasks, stimuli can trigger retrieval of the
      associated, competing task, provoking larger time costs.

PMID- 12809681
TI  - The transfer of abstract principles governing complex adaptive systems.
AB  - Four experiments explored participants' understanding of the abstract principles
      governing computer simulations of complex adaptive systems. Experiments 1, 2, and
      3 showed better transfer of abstract principles across simulations that were
      relatively dissimilar, and that this effect was due to participants who performed
      relatively poorly on the initial simulation. In Experiment 4, participants showed
      better abstract understanding of a simulation when it was depicted with concrete
      rather than idealized graphical elements. However, for poor performers, the
      idealized version of the simulation transferred better to a new simulation
      governed by the same abstraction. The results are interpreted in terms of
      competition between abstract and concrete construals of the simulations.
      Individuals prone toward concrete construals tend to overlook abstractions when
      concrete properties or superficial similarities are salient.

PMID- 12809682
TI  - Forebrain neurons with collateral projections to both the interstitial nucleus of
      the posterior limb of the anterior commissure and the nucleus of the solitary
      tract in the rat.
AB  - The interstitial nucleus of the posterior limb of the anterior commissure (IPAC)
      receives inputs from several autonomic/limbic regions in the forebrain, including
      the agranular insular cortex, bed nucleus of the stria terminalis, the amygdaloid
      complex, and the lateral hypothalamic area. We sought to identify the
      distribution of afferent sources to the IPAC and to determine whether these IPAC
      projection fibers issue collaterals to the nucleus of the solitary tract (NTS),
      the principal relay of primary visceral afferents. Two fluorescent tracers,
      FluoroGold and FluoroRed, were centered stereotaxically on the IPAC and the NTS
      on chloral hydrate-anesthetized Sprague-Dawley rats. Although the majority of
      IPAC and NTS afferents were spatially segregated, small but substantial numbers
      of dually labeled neurons (three to four cells/section) were observed in the
      dorsal bank of the posterior agranular insular cortex, exclusively in layer V.
      Collateral projection neurons were also found in the posterior part of the
      lateral hypothalamic area (two to six cells/section). The branching projections
      identified here may represent a potential link between affective or motivated
      behavior and viscerosensory processing.

PMID- 12809683
TI  - Casein kinase ii (protein kinase ck2) regulates serotonin 5-ht(3) receptor
      channel function in ng108-15 cells.
AB  - We have used whole-cell recording techniques in the mouse neuroblastoma X rat
      glioma hybrid NG108-15 cell line to test whether protein kinase CK2 (CK2; also
      known as casein kinase II) modulates the function of the serotonin 5-HT(3)
      receptor (5-HT(3)R) channel. The rapid application of 5-HT (50 microM) to NG108
      15 cells elicits a 5-HT(3)R-mediated inward current response that rapidly reaches
      peak amplitude and then desensitizes in the continued presence of agonist.
      Internal dialysis with CK2 (20 micrograms/ml) via the patch pipette significantly
      increases the amplitude and decreases the rate of desensitization of the 5-HT(3)R
      mediated responses. CK2 that had been heat-inactivated has no effect on either
      the amplitude or the kinetics of desensitization of the 5-HT(3)R responses. These
      data suggest that dialysis with protein kinase CK2 significantly enhanced current
      through the 5-HT(3)R channel, and that CK2 may be an important regulator of 5
      HT(3)R channel function in the nervous system, possibly serving to facilitate the
      5-HT-induced excitation of the cells.

PMID- 12809684
TI  - Arrested neuronal proliferation and impaired hippocampal function following
      fractionated brain irradiation in the adult rat.
AB  - The generation of new neurons in the adult mammalian brain has been documented in
      numerous recent reports. Studies undertaken so far indicate that adult
      hippocampal neurogenesis is related in a number of ways to hippocampal
      function.Here, we report that subjecting adult rats to fractionated brain
      irradiation blocked the formation of new neurons in the dentate gyrus of the
      hippocampus. At different time points after the termination of the irradiation
      procedure, the animals were tested in two tests of short-term memory that differ
      with respect to their dependence on hippocampal function. Eight and 21 days after
      irradiation, the animals with blocked neurogenesis performed poorer than controls
      in a hippocampus-dependent place-recognition task, indicating that the presence
      of newly generated neurons may be necessary for the normal function of this brain
      area. The animals were never impaired in a hippocampus-independent object
      recognition task. These results are in line with other reports documenting the
      functional significance of newly generated neurons in this region. As our
      irradiation procedure models prophylactic cranial irradiation used in the
      treatment of different cancers, we suggest that blocked neurogenesis contributes
      to the reported deleterious side effects of this treatment, consisting of memory
      impairment, dysphoria and lethargy.

PMID- 12809685
TI  - Effects of postischemic environment on transcription factor and serotonin
      receptor expression after permanent focal cortical ischemia in rats.
AB  - Housing rats in an enriched environment improves functional outcome after
      ischemic stroke, this may reflect neuronal plasticity in brain regions outside
      the lesion. Which components of the enriched environment that are of greatest
      importance for recovery after brain ischemia is uncertain. We have previously
      found that enriched environment and social interaction alone both improve
      functional recovery after focal cerebral ischemia, compared with isolated housing
      with voluntary wheel-running. In this study, the aim was to separate components
      of the enriched environment and investigate the effects on some potential
      mediators of improved functional recovery; such as the inducible transcription
      factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the
      glucocorticoid and serotonin systems. After permanent middle cerebral artery
      occlusion, rats were divided into four groups: individually housed with no
      equipment (deprived group), individually housed with free access to a running
      wheel (running group), housed together in a large cage with no equipment (social
      group) or in a large cage furnished with exchangeable bars, chains and other
      objects (enriched group). mRNA expression of inducible transcription factors,
      serotonin and glucocorticoid receptors was determined with in situ hybridisation
      1 month after cerebral ischemia. Rats housed in enriched or social environments
      showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical
      regions outside the lesion and in the CA1 (cornu ammonis region of the
      hippocampus), compared with isolated rats with or without a running wheel. NGFI-A
      and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to
      functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT(1A)) mRNA expression
      and binding, as well as 5-HT(2A) receptor mRNA expression were decreased in the
      hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor
      gene expression was increased in the dentate gyrus amongst wheel-running rats. No
      group differences were found in plasma corticosterone levels or mRNA levels of
      glucocorticoid receptor, corticotropin-releasing hormone, 5-HT(2C) or c-fos. In
      conclusion, we have found that social interaction is a major component of the
      enriched environment regarding the effects on NGFI-A and NGFI-B expression. These
      transcription factors may be important mediators of improved functional recovery
      after brain infarctions, induced by environmental enrichment.

PMID- 12809686
TI  - Characteristics of late Na(+) current in adult rat small sensory neurons.
AB  - Na(+) currents were recorded using patch-clamp techniques from small-diameter
      (<25 micrometers) dorsal root ganglion neurons, cultured from adult rats (>150
      g). Late Na(+) currents maintained throughout long-duration voltage-clamp steps
      (>/=200 ms) were of two types: a low-threshold, tetrodotoxin-sensitive (TTX-s)
      current that was largely blocked by 200 nM TTX, and a high-threshold, TTX
      resistant (TTX-r) current. TTX-s late current was found in approximately 28%
      (10/36) of small-diameter neurons and was recorded only in neurons exhibiting TTX
      s transient current. TTX-s transient current activation/inactivation gating
      overlap existed over a narrow potential range, centered between -30 and -40 mV,
      whereas late current operated over a wider range. The kinetics associated with de
      inactivation of TTX-s late current were slow (tau approximately 37 ms at -50 mV),
      strongly suggesting that different subpopulations of TTX-s channel generate
      transient and late current. High-threshold TTX-r late current was only present in
      neurons generating TTX-r transient current. TTX-r late current operated over the
      same potential range as that for TTX-r transient current activation/inactivation
      gating overlap, and activation/inactivation gating overlap could be measured even
      after 1.5-s-duration pre-pulses. We suggest that TTX-s late sodium current
      results from channel openings different from those generating transient current.
      As in large-diameter sensory neurons, TTX-s channels generating late openings may
      play a key role in controlling membrane excitability. In contrast, a single
      population of high-threshold TTX-r channels may account for both transient and
      late TTX-r currents.

PMID- 12809687
TI  - Creatine supplementation and riluzole treatment provide similar beneficial
      effects in copper, zinc superoxide dismutase (G93A) transgenic mice.
AB  - This study investigated the effects of riluzole (Ril), creatine (Cr) and a
      combination of these treatments on the onset and progression of clinical signs
      and neuropathology in an animal model of familial amyotrophic lateral sclerosis,
      the G93A transgenic mouse (n=13-17 per group). The onset of clinical signs was
      delayed (P<0.05) by about 12 days in all treatment groups compared with control;
      however, no differences occurred between treatments. All animals were killed at
      199 days of age. At the end of the experimental period the severity of clinical
      signs was less (P<0.05) with all treatments compared with control. Again no
      differences between treatments were observed. The treatments had no effect on the
      number of neurons in ventral horns of the lumbar region of the spinal cord.
      Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in
      cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These
      data demonstrate that treatment with Ril and Cr were both effective in delaying
      disease onset and clinical disability. To the age of killing, no additional
      benefit was conferred by co-administration of Ril and Cr.

PMID- 12809688
TI  - Potential cognitive actions of (n-propargly-(3r)-aminoindan-5-yl)-ethyl, methyl
      carbamate (tv3326), a novel neuroprotective agent, as assessed in old rhesus
      monkeys in their performance of versions of a delayed matching task.
AB  - (N-propargyl-(3R)-aminoindan-5-yl)-ethyl, methyl carbamate (TV3326), a known
      neuroprotective agent exhibiting the properties of both an inhibitor of monoamine
      oxidase (brain selective) and an inhibitor of acetylcholinesterase was
      administered to seven old rhesus monkeys well trained to perform versions of a
      delayed matching-to-sample (DMTS) task. An increasing dose regimen of TV3326 was
      administered orally according to a schedule that allowed the animals to perform
      the standard DMTS task and a self-titrating version of the DMTS task each week
      during the study. A distractor version of the task was administered during two of
      the doses of TV3326. Under the conditions of this experiment TV3326 failed to
      significantly affect accuracy on the standard DMTS task; however, the drug was
      very effective in improving the ability of subjects to titrate to longer-duration
      delay intervals in the titrating version of the task. The maximal drug-induced
      extension of the self-titrated delay interval amounted to a 36.7% increase above
      baseline. This increase in maximum delay duration occurred without a significant
      change in overall task accuracy. TV3326 also significantly improved task accuracy
      during distractor (interference) sessions. The compound was effective enough to
      return group performance efficiency to standard DMTS vehicle levels of accuracy.
      These results were independent of whether trials were associated with a
      distractor or non-distractor delay interval, and they were independent of delay
      interval. The lack of delay selectivity in task improvement by TV3326 may not be
      consistent with a selective effect on attention. TV3326 was not associated with
      any obvious side effect or untoward reaction of the animals to the drug. Thus,
      TV3326 may be expected to offer a significant positive cognitive outcome in
      addition to its reported neuroprotective action.

PMID- 12809689
TI  - Regional variations and age-related changes in nitric oxide synthase and arginase
      in the sub-regions of the hippocampus.
AB  - L-arginine can be metabolised by nitric oxide synthase (NOS) with the formation
      of L-citrulline and nitric oxide (NO), or arginase with the production of L
      ornithine and urea. In contrast to studies showing a potential involvement of
      NOS/NO in the aging process, the role of arginase has not been well documented.
      The present study investigates for the first time the regional variations and age
      related changes in both NOS and arginase in sub-regions of the hippocampus. In
      young adult rats, although the total NOS activity was not significantly different
      across the hippocampal CA1, CA2/3 and the dentate gyrus (DG) sub-regions, the
      total arginase activity showed a clear regional variation with the highest level
      in DG. Western blotting revealed that the highest levels of neuronal NOS (nNOS)
      and endothelial NOS (eNOS) proteins were located in CA1. Arginase I is expressed
      at a very low level in the brain (the whole hippocampus) as compared with the
      liver. By contrast, arginase II protein shows an extremely high expression in the
      brain with little or no expression in the liver. There was no regional variation
      in arginase I or arginase II protein expression across the sub-regions of the
      hippocampus. When a comparison was made between young (4-month-old) and aged (24
      month-old) rats, a significant increase in total NOS activity was found in DG and
      significant decreases in arginase activity were observed in the CA1 and CA2/3
      regions in the aged animals. Western blotting further revealed a dramatic
      decrease in eNOS protein expression in aged CA2/3 with no age-associated changes
      in nNOS, arginase I and II protein expression in any region examined.
      Interestingly, evidence of activity or protein expression of the inducible
      isoform of NOS (iNOS) was not detected in any tissue from either group. The
      present results, in conjunction with previous findings, support the contribution
      of NOS/NO to aging but question the involvement of iNOS in the normal aging
      process. Region-specific changes in arginase suggest that this enzyme may also
      contribute to aging.

PMID- 12809690
TI  - Spatiotemporal transcription of connexin45 during brain development results in
      neuronal expression in adult mice.
AB  - Characterization of the expression pattern of connexins in neural tissue is a
      necessary prerequisite for understanding the functional relevance of the
      corresponding gap junction channels in brain. Here we describe the cell type
      specific expression of connexin45 in the CNS and the spatiotemporal expression
      pattern from embryonic day 19.5 to adult brain using a recently described
      connexin45 LacZ-reporter mouse. The connexin45 gene is highly expressed during
      embryogenesis and up to 2 weeks after birth in nearly all brain regions.
      Afterward its expression is restricted to the thalamus, the CA3 region of
      hippocampus and the cerebellum. In adult mouse brain, the pattern of LacZ
      staining in combination with the analysis of different neuronal and glial marker
      proteins strongly suggests that connexin45 is expressed in neurons, but
      presumably not in astrocytes or mature oligodendrocytes. Expression of the
      LacZ/connexin45 reporter gene in subsets of neurons, such as cerebral cortical,
      hippocampal and thalamic neurons as well as basket and stellate cells of
      cerebellum should be corroborated by functional investigations of connexin45
      protein in electrical synapses. Based on its expression pattern during
      development, we suggest that the connexin45-containing gap junction channels have
      a rather ubiquitous role during brain development and may contribute to
      functional specification in certain subsets of neurons in the adult brain.

PMID- 12809691
TI  - Phosphorylation of extracellular signal-regulated kinases 1/2 is predominantly
      enhanced in the microglia of the rat spinal cord following dorsal root
      transection.
AB  - The present study was initiated to investigate the role of extracellular signal
      regulated kinases (ERK) 1/2 signaling pathway in the early response of spinal
      cord and associated dorsal root ganglion (DRG) to rhizotomy by using Western
      blotting and immunohistochemical techniques in a rat model of L3 and L4 dorsal
      root transection. The results showed that there were a considerable amount of
      total and phosphorylated ERK 1/2 protein in both spinal cord and DRG in normal
      animals killed under pentobarbital anesthesia. The total ERK 1/2 distributed in
      both glia and neurons, while phosphorylated ERK 1/2 dominantly existed in the
      latter in the gray matter of spinal cord, as demonstrated with double
      immunofluorescent staining. Twenty-four and forty-eight hours after axotomy, the
      phosphorylation level of ERK 1/2 in the operation side of dorsal spinal cord was
      much higher than that in the contralateral side, while the total ERK 1/2 level
      seemed unchanged. The increased expression of Fos protein was also seen in the
      dorsal spinal cord at lesion side twelve and twenty-four hours after axotomy.
      Double fluorescent staining proved that the phosphorylated ERK 1/2 positive cells
      in the ipsilateral dorsal spinal cord after axotomy predominantly were microglia
      and small portion was oligodendrocytes, whereas the Fos expression was mainly in
      neurons. In normal DRG, most neurons, especially the medium and small-sized ones,
      and the satellite cells contained total ERK 1/2-like immunoreactivity, whereas
      only a small portion of neurons and satellite cells contained phosphorylated ERK
      1/2. After unilateral dorsal rhizotomy, there were no detectable changes for the
      phosphorylation of ERK 1/2 in either neurons or satellite cells in
      DRG.Collectively, the present results suggest that both ERK and Fos signal
      pathways involve the cellular activation in the spinal cord following dorsal
      rhizotomy, with ERK mainly in microglia and Fos in neurons. The increase of
      phosphorylation of ERK 1/2 in microglia of spinal cord after rhizotomy implicates
      that ERK signaling pathway involves intracellular activity of microglia
      responding to the experimental injury.

PMID- 12809692
TI  - Precursor-protein convertase 1 gene expression in the mouse hypothalamus:
      differential regulation by ob gene mutation, energy deficit and administration of
      leptin, and coexpression with prepro-orexin.
AB  - The expression of precursor-protein convertase (PC)1, PC2 and paired basic amino
      acid cleaving enzyme four mRNA was studied by in situ hybridisation in regions of
      the hypothalamus involved in energy regulation in relation to obese (ob) gene
      mutation and energy deficit. PC1 gene was differentially expressed in
      hypothalamic nuclei of mice from different genetic backgrounds or energetic
      status, whereas no differences in expression were observed for either the PC2 or
      paired basic amino acid cleaving enzyme four genes. In obese ob/ob mice, PC1 mRNA
      levels were increased in the paraventricular nucleus, decreased in the lateral
      hypothalamus and unchanged in the ventromedial nucleus and arcuate nucleus
      relative to lean controls. In response to intraperitoneal injection of murine
      leptin, PC1 mRNA levels in obese ob/ob mice decreased in the arcuate nucleus,
      increased in the lateral hypothalamus and were unchanged in both the
      paraventricular nucleus and ventromedial nucleus. In mice deprived of food for 24
      h, PC1 mRNA levels were reduced in the ventromedial nucleus, increased in the
      lateral hypothalamus and unchanged in the paraventricular nucleus and arcuate
      nucleus relative to ad libitum-fed controls. Overall, whilst the data show
      effects related to leptin and energetic status, they do not support a strong and
      consistent link between PC1 gene expression and energy balance. This suggests
      that if PC1 is important to the control of energy balance then protein expression
      and activity, rather than gene expression may be the more critical parameters of
      regulation. The relationship between PC1 and candidate energy balance-related
      genes in the lateral hypothalamus was investigated by dual in situ hybridisation.
      PC1 mRNA was localised in prepro-orexin mRNA expressing neurons in the lateral
      hypothalamus, which suggests a functional relationship.

PMID- 12809693
TI  - The influence of specific noradrenergic and serotonergic lesions on the
      expression of hippocampal brain-derived neurotrophic factor transcripts following
      voluntary physical activity.
AB  - Previous studies have shown that hippocampal brain-derived neurotrophic factor
      (BDNF) mRNA levels are significantly increased in rats allowed free access to
      exercise wheels and/or administered antidepressant medications. Enhancement of
      BDNF may be crucial for the clinical effect of antidepressant interventions.
      Since increased function of the noradrenergic and/or serotonergic systems is
      thought to be an important initial mechanism of antidepressant medications, we
      sought to test the hypothesis that noradrenergic or serotonergic function is
      essential for the increased BDNF transcription occurring with exercise. In
      addition, individual transcript variants of BDNF were examined, as evidence
      exists they are differentially regulated by discrete interventions, and are
      expressed in distinct sub-regions of the hippocampus. The neurotransmitter system
      specific neurotoxins p-chloroamphetamine (serotonergic) and N-(2-chloroethyl)-N
      ethyl-2-bromobenzylamine (noradrenergic) were administered to rats prior to
      commencing voluntary wheel-running activity. In situ hybridization experiments
      revealed an absence of exercise-induced full-length BDNF mRNA elevations in the
      hippocampi of noradrenergic-lesioned rats. In addition, the striking elevation of
      the exon I transcript in the dentate gyrus was removed with this noradrenergic
      lesion. In contrast, other transcript variants (exons II and III) were elevated
      in several hippocampal regions as a result of this lesion. In serotonin-lesioned
      rats, the significant increases in full-length BDNF, exon I and exon II mRNA
      levels were sustained without alteration (with the exception of exon IV in the
      cornus ammonis subregion 4, CA4). Overall, these results indicate that an intact
      noradrenergic system may be crucial for the observed ability of exercise to
      enhance full-length and exon I hippocampal BDNF mRNA expression. In addition,
      these results suggest that the promoter linked to exon I may provide a major
      regulatory point for BDNF mRNA expression in the dentate gyrus. Elevations of
      other exons, such as II and III, may require the activation of separate
      neurotransmitter systems and intracellular pathways.

PMID- 12809694
TI  - The dopamine D1 receptor-rich main and paracapsular intercalated nerve cell
      groups of the rat amygdala: relationship to the dopamine innervation.
AB  - The intercalated cell masses are GABAergic neurons interposed between the major
      input and output structures of the amygdala. Dopaminergic projections to the main
      and paracapsular intercalated islands were examined by determining the
      relationship of the dopamine nerve-terminal networks to the D1-receptor
      immunoreactive staining of cells within the intercalated islands, using double
      fluorescence immunolabelling procedures in combination with confocal laser
      microscopy. The relationship of terminals positive for both tyrosine hydroxylase
      and dopamine beta-hydroxylase (noradrenaline and/or adrenaline) to terminals
      positive for tyrosine hydroxylase but negative for dopamine beta-hydroxylase
      (dopamine terminals) was studied in relation to the D1-receptor immunoreactivity
      in adjacent sections at various rostrocaudal levels. The microscopy and image
      analysis revealed that there was only a minor dopaminergic innervation of the D1
      receptor-immunoreactive cells in the rostromedial and caudal component of the
      main intercalated island, suggesting volume transmission as the main
      communication mode for dopamine in these regions. In contrast, the D1 receptor
      immunoreactive areas in the rostrolateral part of the main island and also the
      paracapsular intercalated islands showed a high degree of dopaminergic
      innervation, indicating that synaptic and perisynaptic dopamine transmission
      plays a dominant role in these regions. It is known that amygdala neurons are
      involved in the elicitation and learning of fear-related behaviors. We suggest
      that slow dopaminergic volume transmission in the rostromedial and caudal parts
      of the main intercalated island may have a role in tonic excitatory modulation in
      these parts of the main island, allowing GABAergic activity to develop in the
      central amygdaloid nucleus and thereby contributing to inhibition of fear-related
      behavioral and autonomic responses. In contrast, a faster synaptic and
      perisynaptic dopaminergic transmission in the rostrolateral part of the main
      intercalated island and in the paracapsular intercalated islands may have a role
      in allowing a more rapid elicitation of fear-related behaviors.

PMID- 12809695
TI  - Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein
      expression and pain behavior in a rat model of inflammation.
AB  - Activation of cannabinoid CB(2) receptors attenuates thermal nociception in
      untreated animals while failing to produce centrally mediated effects such as
      hypothermia and catalepsy [Pain 93 (2001) 239]. The present study was conducted
      to test the hypothesis that activation of CB(2) in the periphery suppresses the
      development of inflammatory pain as well as inflammation-evoked neuronal activity
      at the level of the CNS. The CB(2)-selective cannabinoid agonist AM1241 (100, 330
      micrograms/kg i.p.) suppressed the development of carrageenan-evoked thermal and
      mechanical hyperalgesia and allodynia. The AM1241-induced suppression of
      carrageenan-evoked behavioral sensitization was blocked by the CB(2) antagonist
      SR144528 but not by the CB(1) antagonist SR141716A. Intraplantar (ipl)
      administration of AM1241 (33 micrograms/kg ipl) suppressed hyperalgesia and
      allodynia following administration to the carrageenan-injected paw but was
      inactive following administration in the contralateral (noninflamed) paw,
      consistent with a local site of action. In immunocytochemical studies, AM1241
      suppressed spinal Fos protein expression, a marker of neuronal activity, in the
      carrageenan model of inflammation. AM1241 suppressed carrageenan-evoked Fos
      protein expression in the superficial and neck region of the dorsal horn but not
      in the nucleus proprius or the ventral horn. The suppression of carrageenan
      evoked Fos protein expression induced by AM1241 was blocked by coadministration
      of SR144528 in all spinal laminae. These data provide evidence that actions at
      cannabinoid CB(2) receptors are sufficient to suppress inflammation-evoked
      neuronal activity at rostral levels of processing in the spinal dorsal horn,
      consistent with the ability of AM1241 to normalize nociceptive thresholds and
      produce antinociception in inflammatory pain states.

PMID- 12809696
TI  - Substantia nigra pars reticulata GABA is involved in the regulation of operant
      lever pressing: pharmacological and microdialysis studies.
AB  - Substantia nigra pars reticulata (SNr) is an important mesencephalic nucleus that
      functions as a relay area for basal ganglia output. SNr receives GABAergic inputs
      from the neostriatum and globus pallidus, and in turn sends projections to a
      variety of motor areas. Although a large number of studies have focused upon the
      behavioral functions of basal ganglia dopamine, much less is known about the
      behavioral functions of SNr GABA. The present studies were undertaken to
      investigate the role of SNr GABA in lever pressing behavior. In the first
      experiment, the GABA(A) antagonist bicuculline was infused locally into SNr to
      determine if blockade of GABA receptors interfered with the performance of lever
      pressing on a fixed ratio 5 schedule. SNr injections of bicuculline produced a
      dose-related suppression of operant responding. Analysis of interresponse time
      bins showed that SNr bicuculline produced a response slowing characterized by a
      relative reduction in the number of fast interresponse times, and an increase in
      the relative number of pauses. In an additional experiment, microdialysis methods
      were used to determine if extracellular GABA is elevated during the performance
      of fixed ratio five lever pressing. During the 30 min lever pressing session,
      extracellular GABA showed a significant and substantial increase relative to
      baseline levels. These data support the hypothesis that SNr GABA is involved in
      the regulation of motor output, and indicate that GABA release in this structure
      is increased during behavioral stimulation.

PMID- 12809697
TI  - Implication of brain-derived neurotrophic factor in the release of dopamine and
      dopamine-related behaviors induced by methamphetamine.
AB  - It is widely recognized that methamphetamine enhances the release of dopamine at
      dopaminergic neuron terminals of the mesolimbic system, which induces dopamine
      related behaviors. Brain-derived neurotrophic factor (BDNF), a neurotrophin,
      binds to and activates its specific receptor tyrosine kinase, TrkB. BDNF has been
      shown to influence the release of dopamine in the mesolimbic dopamine system. The
      present study was designed to investigate roles of BDNF and TrkB in the
      expression of methamphetamine-induced dopamine release in the nucleus accumbens
      and dopamine-related behaviors induced by methamphetamine in rats.
      Methamphetamine (1 mg/kg, s.c.) produced a substantial increase in the
      extracellular levels of dopamine and induced a progressive augmentation of
      dopamine-related behaviors such as rearing and sniffing. In contrast, both the
      stimulation of dopamine release and induction of dopamine-related behaviors by
      methamphetamine were significantly suppressed by pretreatment with intra-nucleus
      accumbens injection of either BDNF (2.0 microl/rat, 1:1000, 1:300 and 1:100) or
      TrkB (2.0 microl/rat, 1:1000 and 1:100) antibody. Furthermore, the basal level of
      dopamine in the nucleus accumbens was not affected by treatment with both BDNF
      and TrkB antibodies. These findings provide further evidence that BDNF/TrkB
      pathway is implicated in the methamphetamine-induced release of dopamine and the
      induction of dopamine-related behaviors.

PMID- 12809698
TI  - Relative involvement of globus pallidus and subthalamic nucleus in the regulation
      of somatodendritic dopamine release in substantia nigra is dopamine-dependent.
AB  - Previously, we have shown that GABA(A) receptors and glutamate receptors in
      substantia nigra play distinct roles in the regulation of somatodendritic
      dopamine release. GABAergic input to substantia nigra was found to be the primary
      determinant of the level of spontaneous somatodendritic dopamine release. In
      contrast, acute blockade of dopamine receptors by systemic haloperidol
      administration produced an increase in somatodendritic dopamine release in
      substantia nigra that was found to be dependent exclusively upon activation of
      nigral glutamate receptors. The focus of the present study was to identify
      anatomical structures that may participate in the differential regulation of
      somatodendritic dopamine release by GABA and glutamate under these two
      conditions. To this end, we pharmacologically inhibited the activity of either
      globus pallidus or subthalamic nucleus using microinfusion of the GABA(A)
      receptor agonist muscimol. The effects of these manipulations on spontaneous
      efflux of somatodendritic dopamine and on increases in this measure produced by
      systemic haloperidol administration were determined in ipsilateral substantia
      nigra using in vivo microdialysis. As observed previously, administration of
      haloperidol (0.5 mg/kg, i.p.) significantly increased extracellular dopamine in
      substantia nigra. Microinfusion of muscimol (400 ng/200 nl) into globus pallidus
      also produced a significant increase in somatodendritic dopamine efflux. When
      haloperidol was administered systemically in conjunction with microinfusion of
      muscimol into globus pallidus, an increase in nigral dopamine efflux was observed
      that was significantly greater than that which was produced singly by muscimol
      microinfusion into globus pallidus or by systemic haloperidol administration. The
      additive nature of the increases in somatodendritic dopamine release produced by
      these two manipulations indicates that independent neural circuitries may be
      involved. Inactivation of subthalamic nucleus by microinfusion of muscimol (200
      ng/100 nl) had no effect on spontaneous somatodendritic dopamine efflux. Muscimol
      application into subthalamic nucleus, however, completely abolished the
      stimulatory effect of systemic haloperidol on dendritic dopamine efflux in
      substantia nigra. The present data extend our previous findings by demonstrating:
      1) an important involvement of globus pallidus efferents in the GABAergic
      regulation of somatodendritic dopamine efflux in substantia nigra under normal
      conditions and, 2) an emergent predominant role of subthalamic nucleus efferents
      in the glutamate-dependent increase in somatodendritic dopamine efflux observed
      after systemic haloperidol administration. Thus, the relative influence of globus
      pallidus and subthalamic nucleus in the determination of the level of
      somatodendritic dopamine release in substantia nigra qualitatively varies as a
      function of dopamine receptor blockade. These findings are relevant to current
      models of basal ganglia function under both normal and pathological conditions,
      e.g. Parkinson's disease.

PMID- 12809699
TI  - Morphine induction of c-fos expression in the rat forebrain through glutamatergic
      mechanisms: role of non-n-methyl-D-aspartate receptors.
AB  - Acute injection of morphine induces expression of the immediate-early genes c-Fos
      and JunB in several forebrain regions of the rat, in part through an N-methyl-D
      aspartate (NMDA) receptor-dependent mechanism. Because membrane depolarization
      through (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      glutamate receptors is believed to be necessary for full activation of NMDA
      receptors, we determined the role of AMPA receptors in morphine-induced c-Fos
      expression. Rats were given the AMPA receptor antagonist GYKI-52466 (12.9 mg/kg,
      i.p.) 15 min before morphine (10 mg/kg, s.c.), or the AMPA receptor enhancer
      CX516 (30 mg/kg, i.p.) 5 min after morphine. The c-Fos response was attenuated by
      the antagonist and augmented by the enhancer. Using double immunocytochemistry,
      we found that morphine induced c-Fos in neurons containing the GluR2/3, but not
      the GluR1 and rarely the GluR4, subunits of the AMPA receptor. Double
      immunocytochemistry for mu opioid receptor and c-Fos showed that c-Fos expression
      was mainly absent in the patch compartment of the striatum, which is enriched in
      mu opioid receptors. The glutamatergic synapse often contains metabotropic
      receptors as well as ionotropic receptors. Type I metabotropic glutamate
      receptors are coupled to activation of protein kinase C, which has also been
      shown to mediate the immediate-early gene response to morphine. To determine if
      activation of metabotropic glutamate receptors is involved in rapid effects of
      morphine on the brain, rats were given the type I metabotropic glutamate receptor
      antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.2 mg/kg, i.p.) or
      vehicle 30 min before morphine treatment. Pretreatment with AIDA completely
      blocked morphine-induced c-Fos expression in the caudate-putamen.Taken together,
      these results demonstrate involvement of both AMPA and type I metabotropic
      glutamate receptors in the acute effects of morphine on the forebrain, supporting
      an important role for glutamatergic neurotransmission mediated by non-NMDA
      glutamate receptors in morphine's actions.

PMID- 12809700
TI  - Experience-dependent regulation of synaptic zinc is impaired in the cortex of
      aged mice.
AB  - Zinc plays an important role in synaptic signaling in the mammalian cerebral
      cortex. Zinc is sequestered into presynaptic vesicles of subpopulations of
      glutamatergic neurons and is released by depolarization, in a calcium-dependent
      manner. As the majority of mechanisms that have been suggested to participate in
      experience-dependent alterations in synaptic strength in the cerebral cortex
      implicate signaling by glutamate, it stands to reason that zincergic signaling
      might also be crucial. Here we show that synaptic zinc is rapidly and dynamically
      modulated in relation to alterations in sensory input and that this response is
      highly age-dependent. Juvenile, adult, and aged mice were subjected to whisker
      removal and levels of staining for synaptic zinc in deprived and non-deprived
      cortical barrels were quantitatively assessed at post-deprivation times ranging
      from 3 h to 21 days. In the first 12 h, zinc levels increased slightly, but
      significantly, in all groups. At later time points, zinc levels increased
      robustly (23%) in the youngest group by 24 h and remained elevated through 7
      days. By contrast, deprivation-induced changes in zinc staining in aged animals,
      achieved their maximal levels at 12 h (approximately 10%) and steadily declined
      thereafter. Adult animals revealed a biphasic, intermediate change with time. In
      all age groups, levels of zinc staining returned to baseline by 21 days after
      whisker plucking. However, only in juvenile and adult mice did we observe that
      the level of zinc staining in deprived barrel hollows, was correlated with the
      length of whiskers as they regrew. Our data suggest that alterations in the
      regulation of synaptic zinc may be involved with decrements of synaptic
      plasticity that accompany senescence.

PMID- 12809701
TI  - Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ
      hybridisation and immunohistochemistry.
AB  - In this study we used in situ hybridisation and double-labelling
      immunohistochemistry to characterise cannabinoid receptor 1 (CB(1)) expression in
      rat lumbar dorsal root ganglion (DRG) neurons.Approximately 25% of DRG neurons
      expressed CB(1) mRNA and displayed immunoreactivity for CB(1). Sixty-nine percent
      to 82% of CB(1)-expressing cells were also immunoreactive for neurofilament 200,
      indicative of myelinated A-fibre neurons, which tend to be large- and medium
      sized DRG neurons (>600 microm(2)). Approximately 10% of CB1-expressing cells
      also expressed transient receptor potential vanilloid family ion channel 2
      (TRPV2), the noxious heat-transducing channel found in medium to large lightly
      myelinated Adelta-fibre DRG neurons. Seventeen percent to 26% of CB(1)-expressing
      cells co-stained using Isolectin B4, 9-10% for calcitonin gene-related peptide
      and 11-20% for transient receptor potential vanilloid family ion channel 1
      (TRPV1), predominantly markers of small non-myelinated C-fibre DRG neurons (<600
      microm(2)). These findings suggest that whilst a wide range of DRG neuron
      phenotypes express CB(1), it is predominantly associated with myelinated fibres.

PMID- 12809702
TI  - Ectopic synaptogenesis during retinal degeneration in the royal college of
      surgeons rat.
AB  - Rod photoreceptor-specific mutations cause ectopic synapses to form between cone
      photoreceptor terminals and rod bipolar cell dendrites in degenerating retinas of
      rhodopsin transgenic (P347L) pigs and retinal degeneration mice. Since the
      mutations occur in rod photoreceptor-specific genes in these two models, it is
      not known if ectopic synaptogenesis occurs specifically due to some rod
      photoreceptor cell-autonomous properties of a mutation or as a general
      consequence of photoreceptor degeneration. In the Royal College of Surgeons (RCS)
      rat, a mutation in the receptor tyrosine kinase gene, Mertk, causes failure of
      the retinal pigment epithelial (RPE) cells to phagocytose shed photoreceptor
      outer segments; subsequently, both rod and cone photoreceptors die. The non
      phagocytic phenotype of the RCS rat is RPE cell-autonomous and the photoreceptors
      degenerate secondarily. Here we show that in 35-day-old RCS rats, where a
      majority of rod and cone photoreceptors remained, rod bipolar cell dendrites had
      abnormal (flat-contact type) synaptic contacts with rod and cone terminals.
      Demonstration of ectopic synapses in the RCS rat suggested that ectopic
      synaptogenesis could occur as a result of photoreceptor degeneration, even when
      the rods and cones were developmentally normal. This further supported the
      hypothesis that ectopic synaptogenesis may be a common step in the disease
      progression of different forms of retinal degeneration that include photoreceptor
      death as a feature, such as retinitis pigmentosa.

PMID- 12809704
TI  - Sexual dimorphism for protein kinase c epsilon signaling in a rat model of
      vincristine-induced painful peripheral neuropathy.
AB  - Painful peripheral neuropathy is a major dose-limiting adverse effect of many
      cancer chemotherapeutic agents, such as the vinca alkaloids and taxanes. Recent
      studies demonstrate sexual dimorphism in second-messenger signaling for primary
      afferent nociceptor sensitization, and a role of second messengers in the models
      of metabolic and toxic painful peripheral neuropathies. This study tested the
      hypothesis that sexual dimorphism alters the severity and second-messenger
      signaling pathways for enhanced nociception in an animal model of vincristine
      induced painful peripheral neuropathy.I.V. injection of vincristine induced
      mechanical hyperalgesia that was greater in female rats. Gonadectomy in the
      females but not the males abolished the sex-dependent difference in mechanical
      hyperalgesia; this effect of gonadectomy in females was reversed by estrogen
      replacement. Inhibition of protein kinase C epsilon (PKC epsilon ) attenuated
      vincristine-induced hyperalgesia in males and ovariectomized females, but not in
      normal females or in estrogen-replaced ovariectomized females. Inhibitors of
      protein kinase A, protein kinase G, p42 / p44-mitogen activated protein kinase
      and nitric oxide synthase also attenuated vincristine-induced hyperalgesia, but
      to a similar degree in both sexes. These data demonstrate an estrogen-dependent
      sexual dimorphism in vincristine-induced hyperalgesia (female>male) and an
      unexpected opposite sexual dimorphism in the contribution of PKC epsilon to the
      severity of this hyperalgesia (male>female).

PMID- 12809703
TI  - The cognitive effects of ovariectomy and estrogen replacement are modulated by
      aging.
AB  - Recent experimental and clinical studies suggest that estrogen may be an
      important factor influencing neuronal function during normal and pathological
      aging. Using different behavioral paradigms in rodents, estrogen replacement was
      shown to enhance learning and memory as well as attenuate learning deficits
      associated with cholinergic impairment. The goal of this study was to determine
      whether cognitive sensitivity to estrogen manipulations (short-term ovariectomy
      and chronic estrogen replacement) is affected by aging. Middle-aged and old
      female Fischer-344 rats were used to estimate the effects of estrogen
      manipulations at two different stages of reproductive aging. At middle age, when
      the females underwent an initial stage of reproductive aging (irregular
      cyclicity), ovariectomy did not significantly affect the acquisition of the T
      maze active avoidance as compared with Sham rats, while estrogen replacement
      decreased behavioral vulnerability to scopolamine. However, when tested at more
      advanced stage of aging (consistent diestrus), old ovariectomized rats were more
      sensitive to scopolamine as compared with the control rats. Moreover, estrogen
      treatment at this age did not produce any protective effect against scopolamine.
      Contrasting findings of the effects of estrogen replacement in middle-aged and
      old rats suggest that the ability of estrogen to enhance the basal forebrain
      cholinergic function declines with age. These data indicate that aging processes
      may substantially modulate the mechanisms of estrogen action. A "time window"
      during which hormone replacement must be initiated in order to be effective could
      be determined in terms of the stages of reproductive senescence. This study is
      the first to clearly demonstrate that the cognitive effects of estrogen
      replacement are still preserved during the initial stages of reproductive aging
      (irregular cyclicity) and dramatically limited as aging progresses (cessation of
      proestrus).

PMID- 12809705
TI  - Integrated contributions of basal forebrain and thalamus to neocortical
      activation elicited by pedunculopontine tegmental stimulation in urethane
      anesthetized rats.
AB  - Efferents from the pedunculopontine tegmentum (PPTg) exert widespread control
      over neocortical electrocorticographic (ECoG) activity and aid in maintaining
      high-frequency ECoG activation during waking and rapid eye movement sleep. The
      mechanisms and subcortical routes that allow the PPTg to influence cortical
      activity remain controversial. We examined the relative contributions of the
      thalamus and basal forebrain in ECoG activation elicited by PPTg stimulation in
      urethane-anesthetized rats. Stimulation (100 Hz, 2 s) of the PPTg suppressed
      large-amplitude, low-frequency oscillations, replacing them with high-frequency
      beta-gamma activity. Systemic administration of the anti-muscarinic drug
      scopolamine (1 mg/kg, i.p.) abolished activation elicited by PPTg stimulation,
      suggestive of an essential role of acetylcholine in this effect. Local infusions
      of lidocaine (1 microl, 1%) into the region of the cholinergic basal forebrain
      complex produced a strong reduction in activation elicited by PPTg stimulation.
      Lidocaine infusions into the reticular thalamic nucleus had no effect, but
      infusions into central thalamus produced a small attenuation of PPTg-evoked
      cortical activation. Combined basal forebrain-central thalamic infusions (1
      microl/site) produced roughly additive effects, leading to a greater loss of
      activation than single-site infusions. These results indicate that, under the
      present experimental conditions, high-frequency cortical ECoG activation elicited
      by the PPTg involves relays in both the basal forebrain and central thalamus,
      with a predominant role of the basal forebrain. After concurrent central thalamic
      basal forebrain inactivation, the forebrain can maintain only limited, short
      lasting activation in response to PPTg stimulation. The additivity of infusion
      effects suggests that, rather than participating in one serial system, basal
      forebrain and central thalamus constitute parallel activating pathways. These
      findings aid in resolving previous controversies regarding the role of thalamus
      and basal forebrain in activation by emphasizing the importance of multiple,
      large-scale networks between brainstem and cortex in regulating the activation
      state of the mammalian neocortex.

PMID- 12809706
TI  - The discharge variability of neocortical neurons during high-conductance states.
AB  - In vivo recordings have shown that the discharge of cortical neurons is often
      highly variable and can have statistics similar to a Poisson process with a
      coefficient of variation around unity. To investigate the determinants of this
      high variability, we analyzed the spontaneous discharge of Hodgkin-Huxley type
      models of cortical neurons, in which in vivo-like synaptic background activity
      was modeled by random release events at excitatory and inhibitory synapses. By
      using compartmental models with active dendrites, or single compartment models
      with fluctuating conductances and fluctuating currents, we found that a high
      discharge variability was always paralleled with a high-conductance state, while
      some active and passive cellular properties had only a minor impact. Furthermore,
      a balance between excitation and inhibition was not a necessary condition for
      high discharge variability. We conclude that the fluctuating high-conductance
      state caused by the ongoing activity in the cortical network in vivo may be
      viewed as a natural determinant of the highly variable discharges of these
      neurons.

PMID- 12809707
TI  - Blockade of nociceptive inhibition of plasma extravasation by opioid stimulation
      of the periaqueductal gray and its interaction with vagus-induced inhibition in
      the rat.
AB  - We have previously shown that stimulation of cutaneous or visceral nociceptors
      suppresses inflammation measured as bradykinin-induced synovial plasma
      extravasation in the knee joint of the rat. This suppression occurs through the
      activation of a spinal as well as a supraspinal reflex pathway leading to
      activation of the adrenal medullae and probably the release of epinephrine. These
      nociceptive-neuroendocrine reflex pathways are tonically inhibited by activity in
      abdominal vagal afferents acting through an inhibitory descending pathway
      projecting through the dorsolateral funiculus (DLF) ipsilateral to the cutaneous
      afferent nociceptive input. Here we investigated whether the descending
      inhibitory pathway acted upon by vagal afferents is also modulated by the
      periaqueductal gray (PAG), similar to other bulbo-spinal pathways acting on
      spinal nociceptive transmission. Injection of morphine sulfate (10 nmol) in the
      ventrolateral PAG significantly inhibited the nociceptive-neuroendocrine reflex
      pathways, an effect that was significantly less after removal of vagal afferents
      (i.e. after release from tonic inhibition maintained by vagal afferents).
      Interruption of the DLF ipsilateral to the nociceptive input removed the
      inhibitory effect of vagal afferents and partly reduced the inhibition produced
      by morphine injected in the PAG. From these investigations we conclude that PAG
      induced inhibition of the nociceptive-neuroendocrine reflex pathways is mediated
      through the DLF ipsilateral to the nociceptive input, involving the same
      descending inhibitory pathway that relays afferent vagal inhibition, and through
      other spinal and possibly supraspinal pathways.

PMID- 12809708
TI  - Chronic stress attenuates glucocorticoid negative feedback: involvement of the
      prefrontal cortex and hippocampus.
AB  - Disruption of the glucocorticoid negative feedback system is observed in
      approximate one half of human depressives, and a similar condition is induced in
      animals by chronic stress. This disruption is thought to involve down-regulation
      of glucocorticoid receptors (GRs) in the feedback sites of the brain. However,
      the responsible site of the brain has not been well elucidated. Here we examined
      the effects of chronic stress induced by water immersion and restraint (2 h/day)
      for 4 weeks followed by recovery for 10 days on the GR levels in the prefrontal
      cortex (PFC), hippocampus, and hypothalamus of rats using a Western immunoblot
      technique. In the PFC, the cytosolic GR levels were decreased, but the nuclear GR
      levels were not changed. In the hippocampus, the levels of cytosolic and nuclear
      GRs were increased. However, there were no marked changes in the GR levels in the
      hypothalamus. The changes in the cytosolic GR levels were confirmed at the mRNA
      level by an in situ hybridization technique. We next examined the suppressive
      effects of dexamethasone (DEX) infusions into these regions on the circulating
      corticosterone levels. When DEX was infused into the PFC or hippocampus of the
      chronically stressed rats, the suppressive response to DEX was abolished, but the
      response was normal in the hypothalamus. In addition, when DEX was injected
      systemically to the chronically stressed rats, the suppressive response to DEX
      was significantly attenuated. These results suggest that the abnormal changes in
      GRs in the higher centers of the hypothalamo-pituitary-adrenal axis are involved
      in the chronic stress-induced attenuation of the feedback. Since dysfunction of
      the PFC or hippocampus is implicated in the pathogenesis of depression, the
      present findings would help to understand the mechanisms underlying the disrupted
      feedback system and its relation to brain dysfunction in depression.

PMID- 12809709
TI  - Exercise induces behavioral recovery and attenuates neurochemical deficits in
      rodent models of Parkinson's disease.
AB  - Exercise is thought to improve motor function and emotional well-being in
      patients with Parkinson's disease (PD). However, it is not clear if the
      improvements are due to neurochemical alterations within the affected
      nigrostriatal region or result from a more general effect of exercise on affect
      and motivation. In this study we show that motorized treadmill running improves
      the neurochemical and behavioral outcomes in two rodent models of PD: the
      unilateral 6-hydroxydopamine (6-OHDA) rat model and bilateral 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) model in aged C57bl mice. Exposure to the
      dopamine (DA) toxins 6-OHDA or MPTP resulted in permanent behavioral and
      neurochemical loss. In contrast, when lesioned animals were exposed to treadmill
      activity two times a day for the first 10 days post-lesion they displayed no
      behavioral deficits across testing days and had significant sparing of striatal
      DA, its metabolites, tyrosine hydroxylase, vesicular monoamine transporter, and
      DA transporter levels compared to lesion sedentary animals. These results
      demonstrate that exercise following nigrostriatal damage ameliorates related
      motor symptoms and neurochemical deficits in rodent models of PD.

PMID- 12809710
TI  - Vanillin.
AB  - Vanillin (4-hydroxy-3-methoxybenzaldehyde) is an important flavour and aroma
      molecule, but is also of interest because of its biogenetic relationship to the
      phenylpropanoid pathway and to other molecules of physiological significance,
      notably salicylate. Recent progress towards characterisation of the biosynthesis
      of vanillin is reviewed. In Vanilla, there is some evidence that the route to
      vanillin-beta-D-glucoside may proceed from 4-coumaric acid via 4
      hydroxybenzaldehyde, with glucoside formation occurring not necessarily as the
      final step, and possibly with the involvement of 4-hydroxybenzyl alcohol beta-D
      glucoside tartrate bis-esters as "shunt" metabolites. This appears to be given
      tentative support by the recent partial characterisation of a 4
      hydroxybenzaldehyde synthase from Vanilla. On the other hand, a well
      characterised, CoA-dependent, non-oxidative chain-shortening mechanism to produce
      vanillin from ferulic acid, occurring as part of a pathway of hydroxycinnamate
      degradation in Pseudomonas, may not be representative of hydroxycinnamate chain
      shortening mechanism(s) occurring in Vanilla and other plants. Nevertheless, by
      expression of the Pseudomonas enzyme 4-hydroxycinnamoyl-CoA hydratase/lyase
      (HCHL), attempts have been made to introduce a direct capacity for vanillin
      formation into model plants by diversion of the phenylpropanoid pathway. The
      results obtained have emphasised the obstacles to achieving the desired oxidation
      level (aldehyde) and ring substitution (4-hydroxy-3-methoxyphenyl), even when a
      substantial metabolic diversion is successfully achieved. Finally, the
      significance of the latest biosynthetic and biotechnological developments is
      reviewed briefly in relation to authentication of vanillin.

PMID- 12809711
TI  - The patatin-like protein from the latex of Hevea brasiliensis (Hev b 7) is not a
      vacuolar protein.
AB  - Upon centrifugation, rubber latex is divided into a layer of rubber particles,
      the cytosol, and the lutoid-body fraction, which is of vacuolar origin. One of
      the proteins isolated from the lutoid-body fraction is a protein with a molecular
      mass of 43 kDa, which has esterase activity on p-nitrophenylpalmitate and which
      shows significant sequence similarity with patatin, a vacuolar protein with
      esterase activity from potato (Solanum tuberosum). This protein is a major
      allergen in rubber latex products (Hev b 7) and can also be isolated from the
      cytosol fraction of rubber latex. The mature protein isolated from lutoid-bodies
      has no structural features expected for a vacuolar protein: the N-terminal
      methionine in the cDNA-derived sequence is cleaved off, the second residue is N
      acetylated, and the C-terminal sequence is identical to that in the cDNA-derived
      sequence. Thus the patatin-like protein in Hevea brasiliensis is not a vacuolar
      protein, but may be associated with not yet characterized particles in the
      cytoplasm, which either sediment with lutoid-bodies or remain in the cytosol
      fraction, depending on the centrifugation conditions.

PMID- 12809712
TI  - Identification of potent inhibitors of Helicoverpa armigera gut proteinases from
      winged bean seeds.
AB  - Dry mature seeds of winged bean (Psophocarpus tetragonolobus L., DC.) (WB)
      contain several proteinase inhibitors. Two-dimensional gel analysis of WB seed
      protein followed by activity visualization using a gel-X-ray film contact print
      technique revealed at least 14 trypsin inhibitors (TIs) in the range of 28-6 kD.
      A total of seven inhibitors (WBTI-1 to 7) were purified by heat treatment and gel
      filtration followed by elution from preparative native gels. Based on their
      biochemical characterization such as molecular mass, pI, heat stability, and
      susceptibility to inactivation by reducing agents, WBTI-1 to 4 are Kunitz type
      inhibitors while WBTI-5 to 7 are classified as Bowman-Birk type serine proteinase
      inhibitors. Although Kunitz type TIs (20-24 kD) of WB have been reported, the
      smaller TIs that belong to the Bowman-Birk type have not been previously
      characterized. Seven major TIs isolated from WB seed were individually assessed
      for their potential to inhibit the gut proteinases (HGP) of Helicoverpa armigera,
      a pest of several economically important crops, which produces at least six major
      and several minor trypsin/chymotrypsin/elastase-like serine proteinases in the
      gut. WBTI-1 (28 kD) was identified as a potent inhibitor of HGP relative to
      trypsin and among the other WBTIs; it inhibited 94% of HGP activity while at the
      same concentration it inhibited only 22% of trypsin activity. WBTI-2 (24 kD) and
      WBTI-4 (20 kD) inhibited HGP activity greater than 85%. WBTI-3,-5,-6 and-7 showed
      limited inhibition of HGP as compared with trypsin. These results indicate that
      WBTIs have different binding potentials towards HGP although most of the HGP
      activity is trypsin-like. We also developed a simple and versatile method for
      identifying and purifying proteinase inhibitors after two-dimensional separation
      using the gel-X-ray film contact print technique.

PMID- 12809714
TI  - Maize stem tissues: ferulate deposition in developing internode cell walls.
AB  - It has been hypothesized that ferulates are only deposited in the primary cell
      wall of grasses. To test this hypothesis, the fourth elongating, above-ground
      internode of maize (Zea mays l.) was sampled from three maize hybrids throughout
      development. Cell wall composition was determined by the Uppsala Dietary Fibre
      method. Ester- and ether-linked ferulates were determined by HPLC analysis of
      ferulic acid released from the internodes by low and high temperature alkaline
      treatments. Internode length increased from 9 to 152 mm over 96 days of growth,
      with elongation being complete in the first 12 days. More than half of the cell
      wall material in the maize internodes accumulated after elongation had ended.
      Deposition of cell wall material appeared to reach its maximum extent 40 days
      after sampling began, well before physiological maturity of the maize plants.
      Galactose and arabinose began to accumulate early in cell wall development which
      was presumed to be associated with primary wall growth during internode
      elongation. The major secondary wall constituents (analyzed as glucose, xylose,
      and Klason lignin) did not begin to accumulate rapidly until shortly before
      internode elongation ended. Ferulate ester deposition began before ferulate
      ethers were observed in the cell wall, but both forms of ferulate continued to
      accumulate in secondary cell walls, long after internode elongation had ceased.
      These data clearly show that contrary to the hypothesis, ferulate deposition was
      not restricted to the primary wall and that active lignin/polysaccharide cross
      linking mediated by ferulates occurs in the secondary wall.

PMID- 12809713
TI  - Use of plant cell cultures to study graminicide effects on lipid metabolism.
AB  - Graminicides belonging to the cyclohexanedione and aryloxyphenoxypropionate
      classes are well established to act by disrupting acyl lipid biosynthesis via
      specific inhibition of acetyl-CoA carboxylase. Species of grass inherently
      resistant to such herbicides, or biotypes of grassy weed species which display
      acquired resistance to recommended rates of graminicide application, are known to
      possess an altered plastidic multifunctional acetyl-CoA carboxylase showing
      reduced sensitivity to these herbicides in vitro. Studies reported here
      demonstrate that cell suspension cultures of maize, a graminicide-sensitive
      species and Poa annua, a graminicide-insensitive species, display a similar
      differential sensitivity of acyl lipid biosynthesis as tissue from corresponding
      intact plants. Acyl lipid biosynthesis in P. annua can be inhibited if
      sufficiently high concentrations of graminicide are used. The major plastidic
      form and the minor cytosolic forms of acetyl-CoA carboxylase were successfully
      purified from maize cell suspensions, were compared to those from leaf tissue and
      were shown to be differentially inhibited by graminicides in a similar manner to
      their counterparts from leaf tissue. These studies demonstrate that cell
      suspensions are useful for studying the mode of action of graminicides,
      especially in view of the limited amount of material obtainable from many grassy
      species which are very fine-growing.

PMID- 12809715
TI  - Rice seedlings release momilactone B into the environment.
AB  - Since the growth inhibitor momilactone B was found recently in root exudates of
      rice (Oryza sativa L.), 3-day-old rice seedlings were transferred to hydroponic
      culture and the level of momilactone B released into the environment from the
      seedlings was measured. At day 15 after transfer, the level of momilactone B in
      the culture solution was 1.8 nmol per seedling compared with endogenous levels of
      0.32 and 0.63 nmol per root and shoot, respectively, suggesting that rice
      seedlings actively releases momilactone B into the culture solution. This release
      must occur from the roots because only rice roots were immersed in the culture
      solution. Momilactone B inhibited the growth of ten cress (Lepidium sativum L.)
      seedlings at concentrations greater than 3 microM. Ten rice seedlings were
      incubated with ten cress seeds in a Petri dish containing 1 ml of medium, the
      medium contained 18 nmol of momilactone B, which came to 18 microM. This level of
      momilactone B was enough to reveal growth inhibition of the cress seedlings.
      Release level of momilactone B and its effectiveness as a growth inhibitor
      suggest that it may play an important role in rice allelopathy.

PMID- 12809716
TI  - Chemical profiling of Ocimum americanum using external flavonoids.
AB  - A HPLC survey was undertaken of the external flavonoids in 111 herbarium
      specimens of Ocimum americanum L. (O. canum Sims), which were largely collected
      from their natural habitats throughout Africa and Asia. The purpose of this study
      was to establish the flavonoid profiles of this species over the full range of
      its geographic distribution in order to use these for authentication purposes.
      Six different external flavonoid chemotypes were found. The major chemotype,
      present in circa 80% of the specimens of both var. americanum and var. pilosum
      collected throughout the distribution area of the species, was characterised by
      very high levels of nevadensin, slightly lower levels of salvigenin and much
      lower levels of up to 15 other external flavones. Of the remaining five
      chemotypes, two were found in var. americanum and three in var. pilosum. All
      specimens belonging to these chemotypes were collected in South or East Africa
      and represented by only a few specimens. These samples contained much smaller
      levels of flavones than present in the major chemotype of O. americanum and all
      lacked nevadensin. Xanthomicrol, a compound absent from the main chemotype, was
      the dominant flavone in two of the minor chemotypes. The external flavonoid
      profiles found in the six chemotypes of O. americanum were compared with those of
      O. x citriodorum (11 herbarium specimens studied) and seven other closely related
      species of Ocimum. The main nevadensin/salvigenin pattern present in O.
      americanum was also found in O. x citriodorum, O. basilicum and some specimens of
      O. minimum, but there were strong quantitative differences in external flavonoids
      among these taxa. The other chemotypes of O. americanum showed some similarities
      in their external flavone profiles to those found in the closely related East
      African species O. fischeri, O. forskolei, O. kenyense and O. kilimandscharicum,
      which occur in the same geographic areas. This suggests that the uncommon
      chemotypes of O. americanum may have originated by an exchange of genes with
      other Ocimum species, e.g. by introgressive hybridisation. Despite some
      similarities in profiles, chemical differences were also found among the species,
      so that it should be possible to authenticate a large proportion of leaf samples
      of O. americanum on the basis of external flavonoid profiles.

PMID- 12809717
TI  - Antimicrobial action of palmarosa oil (Cymbopogon martinii) on Saccharomyces
      cerevisiae.
AB  - The essential oil extracted from palmarosa (Cymbopogon martinii) has proven anti
      microbial properties against cells of Saccharomyces cerevisiae. Low
      concentrations of the oil (0.1%) inhibited the growth of S. cerevisiae cells
      completely. The composition of the sample of palmarosa oil was determined as 65%
      geraniol and 20% geranyl acetate as confirmed by GC-FTIR. The effect of palmarosa
      oil in causing K(+) leakage from yeast cells was attributed mainly to geraniol.
      Some leakage of magnesium ions was also observed. Blocking potassium membrane
      channels with caesium ions before addition of palmarosa oil did not change the
      extent of K(+) ion leakage, which was equal to the total sequestered K(+) in the
      cells. Palmarosa oil led to changes in the composition of the yeast cell
      membrane, with more saturated and less unsaturated fatty acids in the membrane
      after exposure of S. cerevisiae cells to the oil. Some of the palmarosa oil was
      lost by volatilization during incubation of the oil with the yeast cells. The
      actual concentration of the oil components affecting the yeast cells could not
      therefore be accurately determined.

PMID- 12809718
TI  - Allelopathic substances in Pueraria thunbergiana.
AB  - Leaves of Pueraria thunbergiana possess allelopathic activity and the putative
      compounds causing this growth inhibitory effect were isolated from their aqueous
      methanol extract. The chemical structures of these growth inhibitors were
      determined by high-resolution MS and 1H NMR spectral data as cis,trans-xanthoxin
      and trans,trans-xanthoxin. cis,trans-Xanthoxin and trans,trans-xanthoxin
      inhibited the root growth of cress (Lepidium sativum L.) seedlings at
      concentrations greater than 0.3 and 3 microM, respectively. The doses required
      for 50% inhibition on the cress roots were 1.1 and 14 microM for cis,trans- and
      trans,trans-xanthoxin, respectively. The concentrations of cis,trans- and
      trans,trans-xanthoxin in P. thunbergiana leaves were 51.4 and 72.5 ng g(-1) fresh
      weight, respectively. The effectiveness of cis,trans- and trans,trans-xanthoxin
      on the growth inhibition and the occurrence of both xanthoxins in P. thunbergiana
      suggest that xanthoxins may contribute to the growth inhibitory effect of P.
      thunbergiana, and may play an important role in the allelopathy of P.
      thunbergiana after being released into the soil.

PMID- 12809719
TI  - Sesquiterpene constituents from the liverwort Bazzania japonica.
AB  - The hydrodistillation products of the liverwort Bazzania japonica were separated
      by preparative gas chromatography (GC) and investigated by spectroscopic methods.
      Seven unknown compounds were isolated and identified by GC-MS and NMR. Four of
      them, the norsesquiterpene hydrocarbons 4-epi-11-nor-aristola-1(10),11-diene (1),
      4-epi-11-nor-aristola-1,9,11-triene (2), 4-epi-11-nor-aristola-9,11-diene (3),
      and one oxygenated sesquiterpene, (-)-aristol-1(10)-en-12-ol (5) are new natural
      compounds, and one, (+)-himachala-2,4-diene (7), has for the first time been
      isolated from liverworts. The absolute configurations of 5 and 7 were derived by
      chemical correlation reactions and/or enantioselective GC using cyclodextrin
      phases. 1, 2 and 3 have identical absolute configuration.

PMID- 12809720
TI  - A "flavone-polysaccharide" redefined as a mixture of 6-methoxyluteolin penta- and
      hexa-O-glycosides.
AB  - The incomplete structure proposed in 1972 for a unique "flavone-polysaccharide"
      compound, MF-1, from the liverwort Monoclea forsteri, has been re-examined.
      Rather than the proposed 8-methoxyluteolin structure with polysaccharides
      attached to the 7- and 4'-hydroxyls, MF-1 has been shown to be primarily a
      mixture of penta- and hexa-O-glycosides of 6-methoxyluteolin, which are
      accompanied by their luteolin analogues. MS and NMR evidence is marshalled to
      define the structure of MF-la as 6-methoxyluteolin 7-O-[2-O-alpha-rhamnosyl-3-O
      alpha-arabinosyl-beta-glucuronide]-4'-O-[2-O-alpha-rhamnosyl-3-O-beta-xylosyl
      beta-glucuronide], and MF-1b as 6-methoxyluteolin 7-O-[2-O-alpha-rhamnosyl-beta
      glucuronide]-4'-O-[2-O-alpha-rhamnosyl-3-O-beta-xylosyl-beta-glucuronide]. This
      report is the first to provide substantive evidence for the existence of flavone
      penta- and hexa-O-glycosides in nature. The newly defined structure(s) for MF-1
      more closely align M. forsteri with the only other species in the order
      Monocleales, M. gottschei.

PMID- 12809721
TI  - An arylbenzofuran and four isoflavonoids from the roots of Erythrina poeppigiana.
AB  - An arylbenzofuran, erypoegin F and four isoflavonoids, erypoegins G-J, together
      with six known compounds were isolated from the roots of Erythrina poeppigiana,
      and their structures were elucidated on the basis of spectroscopic evidence.
      Erypoegin F is a rare 2-arylbenzofuran possessing a formyl group from a natural
      source, and erypoegin I is the first naturally occurring isoflavonoid with a 2
      oxo-3-methylbutyl group.

PMID- 12809722
TI  - Chemical and cytotoxic constituents from Peperomia sui.
AB  - Three polyketide compounds, surinone A, surinone B, surinone C and one
      acylresorcinol, suranone, along with thirty known compounds, were isolated from
      the whole plant of Peperomia sui. Their structures were elucidated from spectral
      analysis. Several compounds showed cytotoxic activity against HONE-1 and NUGC-3
      cell lines in vitro.

PMID- 12809723
TI  - Aromatic compound glucosides, alkyl glucoside and glucide from the fruit of
      anise.
AB  - From the polar portion of the methanolic extract of the fruit of anise
      (Pimpinella anisum L.), which has been used as a spice and medicine since
      antiquity, four aromatic compound glucosides, an alkyl glucoside and a glucide
      were isolated together with 24 known compounds. The structures of the new
      compounds were clarified as (E)-3-hydroxyanethole beta-D-glucopyranoside, (E)-1'
      (2-hydroxy-5-methoxyphenyl)propane beta-D-glucopyranoside, 3-hydroxyestragole
      beta-D-glucopyranoside, methyl syringate 4-O-beta-D-glucopyranoside, hexane-1,5
      diol 1-O-beta-D-glucopyranoside and 1-deoxy-L-erythritol 3-O-beta-D
      glucopyranoside by spectral investigation.

PMID- 12809724
TI  - The unmasking of lignin structures in wheat straw by alkali.
AB  - This study reports on the structural modifications of wheat straw cell wall
      promoted by potassium carbonate and sodium hydroxide that lead to the unmasking
      of some lignin structures. The first impact of the treatments was the extraction
      of a particular fraction of lignin enriched in C-C linked structures compared to
      the mean composition in reference wheat straw. Concomitantly, an apparent
      increase in the amount of lignin monomers released by the cleavage of alkyl-aryl
      ether bonds was observed in alkali-extracted samples. By summing the amount of
      ether linked monomers analyzed by thioacidolysis in the solubilized lignin to
      that found in the extracted wheat straw, an excess of up to 37% is apparent,
      relative to the corresponding amount in the reference wheat straw. Other
      modifications of the cell wall were also found. Indeed, a fraction of uronic
      acids was lost during the treatments and a new fractionation pattern of the
      lignin-carbohydrate complexes was evidenced. It can thus be concluded that a
      significant proportion of lignin within the cell wall was unmasked after (i) the
      selective removal of a particular lignin fraction, (ii) a partial saponification
      of the esterified fraction of lignin with uronic acids and (iii) a modification
      of the interactions between the cell wall constituents.

PMID- 12809725
TI  - Conodurine, conoduramine, and ervahanine derivatives from Tabernaemontana
      corymbosa.
AB  - Four bisindole alkaloids, viz., 19'(S)-hydroxyconodurine, conodurinine, 19'(S)
      hydroxyconoduramine, and 19'(S)-hydroxyervahanine A, in addition to conodurine
      and ervahanine A, were obtained from the leaf and stem-bark extracts of
      Tabernaemontana corymbosa. The structures of the new alkaloids were determined
      using NMR and MS analysis.

PMID- 12809730
TI  - Bone in the pregnant mother and newborn at birth.
AB  - BACKGROUND: Changes in maternal bone during pregnancy may affect fetal bone
      mineralization. ISSUES: The biphasic changes in maternal bone histology
      (temporary loss of cancellous bone in early pregnancy restored by term gestation)
      are consistent with corresponding blood biochemistry changes; increased bone
      resorption markers in the first trimester, while bone formation markers increased
      in the last trimester. Postpartum bone mineral density (BMD) by DEXA is increased
      at cortical bone and decreased at trabecular bone sites compared with
      prepregnancy values. The mean reduction of spine BMD is 3.5% from prepregnancy to
      immediate postpartum. Neonatal bone mineral content (BMC) is different by season
      of birth, low weight relative to gestation, and having a diabetic mother. Lower
      total body BMC and high bone resorption marker in winter vs. summer-born newborns
      was related to low vitamin D, indicating alterations of fetal bone metabolism by
      maternal D deficiency. Lower BMC and decreased bone formation marker in infants
      born small for gestational age than those born appropriate for gestation may
      relate to reduced transplacental mineral transfer. Low BMC in infants of diabetic
      mother was correlated inversely with poor control of maternal diabetes during
      early pregnancy. CONCLUSIONS: During pregnancy, maternal bone mineral metabolism
      are changed, and influences on fetal bone mineralization occur in utero.

PMID- 12809731
TI  - A review of clinical and laboratory findings and treatment of tumor lysis
      syndrome.
AB  - Acute tumor lysis syndrome (TLS) has started to be considered a separate entity
      or condition associated with bulk tumor treatment. TLS is described as the
      biochemical disturbances associated with rapid destruction of tumor cells with
      subsequent synchronised massive release of cellular breakdown products sufficient
      to overwhelm excretory mechanisms and the body's normal reutilization capacity.
      The cardinal signs of TLS are: hyperkalemia, hyperphosphatemia, hypocalcemia and
      hyperuricemia. This review comprehensively discusses the differential diagnosis,
      pathophysiology and clinical features, possible causal indications for laboratory
      monitoring and treatment options of TLS.

PMID- 12809732
TI  - Analysis of glutathione: implication in redox and detoxification.
AB  - BACKGROUND: Glutathione is a ubiquitous thiol-containing tripeptide, which plays
      a central role in cell biology. It is implicated in the cellular defence against
      xenobiotics and naturally occurring deleterious compounds, such as free radicals
      and hydroperoxides. Glutathione status is a highly sensitive indicator of cell
      functionality and viability. Its levels in human tissues normally range from 0.1
      to 10 mM, being most concentrated in liver (up to 10 mM) and in the spleen,
      kidney, lens, erythrocytes and leukocytes. In humans, GSH depletion is linked to
      a number of disease states including cancer, neurodegenerative and cardiovascular
      diseases. The present review proposes an analysis of the current knowledge about
      the methodologies for measuring glutathione in human biological samples and their
      feasibility as routine methods in clinical chemistry. Furthermore, it elucidates
      the fundamental role of glutathione in pathophysiological conditions and its
      implication in redox and detoxification process. TESTS AVAILABLE: Several methods
      have been optimised in order to identify and quantify glutathione forms in human
      biological samples. They include spectrophotometric, fluorometric and
      bioluminometric assays, often applied to HPLC analysis. Recently, a liquid
      chromatography-mass spectrometry technique for glutathione determination has been
      developed that, however, suffers from the lack of total automation and the high
      cost of the equipment. CONCLUSION: Glutathione is a critical factor in protecting
      organisms against toxicity and disease. This review may turn useful for analysing
      the glutathione homeostasis, whose impairment represents an indicator of tissue
      oxidative status in human subjects.

PMID- 12809733
TI  - Precision and long-term stability of capillary electrophoresis measurement of
      serum protein zones.
AB  - BACKGROUND: Analytical evaluations of an available system for capillary zone
      electrophoresis (CZE) of serum protein have been reported. However, data
      concerning long-term precision and stability of the system, operated under
      routine conditions, are lacking. We report data from an internal quality control
      (QC) scheme, obtained over a 1-year period. METHODS: Measurements were done with
      a pair of instruments (Beckman Paragon CZE 2000 system), each equipped with seven
      capillaries. After preliminary (1 month) assessment of possible inter-capillary
      and inter-instrument variations, the QC material (a home prepared serum pool
      stored in the frozen state) was assayed daily over a 1-year period. RESULTS:
      Maximum inter-capillary and inter-instrument differences were 3.1% and 2.4%. No
      significant trend was observed for daily values (205 measurements over 1 year);
      in the same period overall imprecision values (CV) were in the interval 1.2%
      (albumin) to 3.2-6.1% (globulin zones). Mean monthly imprecision (CV) values were
      in the interval 1.1% (albumin) to 5.2% (globulin zones). There was no significant
      trend of monthly means with time. The observed imprecision values were within the
      biological variation-derived goals for imprecision. CONCLUSIONS: It is concluded
      that the assessed analytical instruments, operated in routine conditions, show
      long-term stability and imprecision consistent with the clinical use of the
      results produced.

PMID- 12809734
TI  - Rapid and reliable genotyping for the Toll-like receptor 4 A896G polymorphism
      using fluorescence-labeled hybridization probes in a real-time polymerase chain
      reaction assay.
AB  - BACKGROUND: The Toll-like receptor 4 (TLR4) is involved in immune response to
      endotoxin as well as the pathogenesis of atherosclerosis. The TLR4 gene was shown
      to carry a single-nucleotide polymorphism (A896G). We developed a rapid-cycle
      polymerase chain reaction (PCR) which allows for rapid genotyping and, therefore,
      may be useful in clinical risk assessment. METHODS: Fluorescently labeled
      oligonucleotide hybridization probes were designed for the LightCycler
      instrument. A PCR product was generated in a single reaction followed by melting
      point analysis. Ninety-three German Caucasians were genotyped. The interleukin
      1beta (IL-1beta) response to endotoxin was assessed after whole blood stimulation
      with endotoxin according to TLR4 genotypes. RESULTS: The method suggested by us
      is a time-saving technique requiring no additional manual steps. Frequencies of
      the A and G allele were 0.95 and 0.05, respectively. The study population was in
      Hardy-Weinberg equilibrium. The specificity of the method was confirmed by
      sequencing. The IL-1beta levels were lower in carriers of the G allele.
      CONCLUSIONS: This PCR assay is a rapid and reliable technique for TLR4
      genotyping.

PMID- 12809735
TI  - Performance characteristics of the Dimension RxL iron and total iron-binding
      capacity methods.
AB  - BACKGROUND: Measurements of serum iron and total iron-binding capacity (TIBC) can
      be used to aid the diagnosis of iron deficiency and iron overload states. A
      variety of different methods for these measurements are commercially available.
      METHODS: Linearity, imprecision and hemoglobin interference of homogeneous iron
      and TIBC methods on a Dimension RxL analyzer were assessed. Method comparison
      studies were performed with a Vitros 950 analyzer. RESULTS: The Dimension RxL
      iron method was linear from 40 to 1000 microg/dl. The coefficient of variation of
      the iron and TIBC methods were <4% and <2%, respectively, at iron concentrations
      of 68 and 228 microg/dl and TIBC concentrations of 206 and 384 microg/dl.
      Comparison of the Vitros 950 and Dimension RxL iron methods gave a slope of 0.97,
      an intercept of 6.0 and r=0.99. Corresponding results for the TIBC methods were
      1.02, -6.6 and r=0.97, respectively. Simulation of acute iron overload in vitro
      did not produce the same effect on TIBC measurements as in vivo overload. Iron
      recovery by the Dimension RxL method was reduced 40-60% by the addition of
      deferoxamine at a concentration of 200 micromol/l. CONCLUSIONS: The Dimension RxL
      assay provides acceptable measurements of iron and TIBC in routine patient
      samples. Iron measurements are unreliable in the presence of deferoxamine.

PMID- 12809736
TI  - A novel colorimetric assay for the determination of lysophosphatidic acid in
      plasma using an enzymatic cycling method.
AB  - BACKGROUND: Several methods for measuring concentrations of lysophosphatidic acid
      (LPA), a lipid mediator, have been reported to date. However, these methods are
      not routinely used because most of them require specialized instrument and a
      complicated protocol. METHODS: We developed a novel LPA assay using enzymatic
      cycling. LPA in a sample is hydrolyzed with lysophospholipase to glycerol-3
      phosphate, followed by enzymatic cycling using glycerol-3-phosphate oxidase and
      glycerol-3-phosphate dehydrogenase. Amplified concentrations of hydrogen
      peroxides, a product of the enzymatic cycling, are then colorimetrically
      measured. RESULTS: This method was specific for LPA, being insensitive to the
      presence of phosphatidic acid or lysophosphatidylcholine. The within-run and
      between-run CVs were 1.31-1.32% and 0.73-1.03%, respectively. The recoveries of
      exogenous LPA added to plasma were 100.3-101.6%. In males, LPA concentrations
      (mean+/-S.D.) of human serum and EDTA-plasma were 0.41+/-0.14 and 0.08+/-0.02
      micromol/l, respectively. In females, they were 0.41+/-0.12 and 0.09+/-0.02
      micromol/l, respectively. CONCLUSIONS: This novel colorimetric assay for
      determination of LPA using enzymatic cycling is simple and highly sensitive. It
      can be used with an automatic analyzer. It may also be useful for further studies
      of the biological functions of LPA as well as clinical applications in various
      disorders.

PMID- 12809737
TI  - Chronic cold exposure affects the antioxidant defense system in various rat
      tissues.
AB  - BACKGROUND: Chronic exposure to stress alters the normal body homeostasis and,
      hence, leads to the development of various human pathologies, which might involve
      alterations in the antioxidant defense system. We studied the effect of chronic
      cold exposure on oxidative stress and antioxidant defense system in various rat
      tissues. METHODS: Male albino rats (Wistar strain), 2-3 months old, were exposed
      to 3 weeks of cold treatment. Antioxidant enzymes, superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and
      glutathione S-transferase (GST) were measured in addition to the antioxidants,
      ascorbic acid (AsA) and glutathione (GSH), and the prooxidants, lipid peroxides
      (LPO) and xanthine oxidase (XOD), in brain, heart, kidney, liver and small
      intestine using standard protocols. RESULTS: Chronic cold exposure resulted in a
      significant increase in LPO in all the tissues studied while XOD was increased in
      the brain and intestine. Total SOD activity was significantly decreased in all
      the tissues, whereas CAT activity was significantly increased in the kidney and
      decreased in heart, liver and intestine in the animals exposed to cold. GPx
      activity was increased only in the brain and intestine of stressed rats. Chronic
      cold exposure resulted in significant decrease in GR activity in heart, liver and
      intestine. GST activity was increased (except heart) and GSH was significantly
      decreased in all the tissues in treated rats. AsA was increased in kidney and
      intestine but decreased in heart of stressed animals. CONCLUSIONS: The observed
      changes in the antioxidant defense system are tissue specific, but it is evident
      that chronic exposure to cold leads to oxidative stress by displacing the
      prooxidant-antioxidant balance of this defense system by increasing the
      prooxidants while depleting the antioxidant capacities.

PMID- 12809738
TI  - Bone mineral density correlates strongly with basal metabolic rate in
      postmenopausal women.
AB  - BACKGROUND: This study investigated the relationships of bone mineral density
      (BMD) with body composition, basal metabolic rate (BMR), and fat distribution.
      METHODS: We measured body mass index (BMI), anthropometrics, and BMD in 345
      postmenopausal women and 224 elderly men. Total body fat (TBF), fat distribution,
      and BMR were assessed using a body composition analyzer. Lumbar spine and
      proximal femur BMDs were measured with dual-energy X-ray absorptiometry. RESULTS:
      Lumbar spine BMD was more strongly correlated with BMR (r=0.51, p<0.01) than with
      lean body mass (r=0.39, p<0.01) and waist hip ratio (r=-0.28, p<0.01) in
      postmenopausal women. The mean values of BMR in osteoporotic women were
      significantly lower than those for non-osteoporotic women (p<0.01). The
      prevalences of osteoporosis at the sites of lumbar spine and proximal femur were
      32.1% and 23.3% in the women with BMR<1230 kcal, which were significantly higher
      than those of osteoporosis (5.4% and 7.7%) at the corresponding sites in the
      women with BMR> or =1230 kcal (p<0.01). In elderly men, the incidence of
      osteoporosis at the proximal femur was 29.5% in the subjects with BMR<1390 kcal,
      significantly higher than that (2.2%) in the subjects with BMR> or =1390 kcal
      (p<0.01). CONCLUSION: BMR is more closely associated with bone density in elderly
      persons, at least as compared to TBF, BMI, or lean body mass.

PMID- 12809739
TI  - Protective effects of CVPM on vascular endothelium in rats fed cholesterol diet.
AB  - BACKGROUND: The cardiovascular protective mixture (CVPM) is a concoction of nine
      Chinese traditional medicines: Dan-shen root, Szechwan lovge rhizome, Chinese
      angelica, Hawthorn fruit, Safflower, Peach seed, Red peony root, earthworm, and
      membranous milkvetch root. These medicines are used to cure cardiovascular
      disease in China. METHODS: Animal models were established by feeding the Sprague
      Dawley (SD) rats with lipid-rich forage. Serum total cholesterol (TC) and low
      density lipoprotein cholesterol (LDL-C) were measured. Malondialdehyde (MDA)
      content was determined to monitor lipid peroxidation. The 6-keto-prostaglandin
      F(1alpha)(6-keto-PGF(1alpha)) concentration was measured by radioimmunoassay to
      investigate the content of prostacyclin (PGI(2)). Electron microscope (JEM
      1200EX) was used to observe the microstructure of the vascular endothelium. Rat
      aortic endothelial cell was cultured to investigate the effect of CVPM on
      vascular endothelial cell in vitro. RESULTS: CVPM inhibited the accumulation of
      TC, LDL-C, and MDA in vivo, when the rats were fed with cholesterol diet. CVPM
      promoted synthesizing and excreting of PGI(2), since it is capable of activating
      the proliferation of vascular endothelium in vitro. Electron micrographs showed
      that CVPM had notable protective effect on the vascular endothelium and prevented
      the shedding of these cells from subendothelial layer. CONCLUSIONS: CVPM could
      ameliorate the internal environment in which vascular endothelial cells lived,
      and activate the proliferation of these cells. Through these mechanisms, CVPM
      protect vascular endothelial cell from being harmed by excess cholesterol in
      vivo.

PMID- 12809742
TI  - Example of use of a desktop scanner for data acquisition in a colorimetric assay.

PMID- 12809740
TI  - Inadequacy of theoretical basis of breath methylated alkane contour for assessing
      oxidative stress.

PMID- 12809743
TI  - Erythrocyte glutathione and serum glutathione-S-transferase in patients with
      brain tumors.

PMID- 12809744
TI  - Importance of midstream clean-catch technique for urinalysis, reconfirmed by
      urinary flow cytometry.

PMID- 12809745
TI  - Effect of total parenteral nutrition products on enzymatic measurements of
      glycated albumin.

PMID- 12809746
TI  - ADHD and stuttering: a tutorial.
AB  - The purpose of this tutorial is twofold. The first is to provide a brief
      description of some of the key diagnostic features of attention deficit
      hyperactivity disorder (ADHD) for speech-language pathologists who might not be
      knowledgeable about this disorder. The second purpose is to provide information
      and suggestions about treating children who stutter and who have been diagnosed
      with ADHD. Specific information is provided regarding medication used to treat
      ADHD symptoms as well as the minimal documented evidence of its impact on
      stuttering. Suggestions for educational, behavioral, and cognitive management of
      children who stutter and have ADHD also are discussed. EDUCATIONAL OBJECTIVES:
      The reader will learn about and be able to: (1) identify diagnostic criteria for
      children with ADHD; (2) differentiate pharmacological, environmental, and
      behavioral interventions for children with ADHD; and (3) examine effective
      instructional techniques for children who stutter and have ADHD.

PMID- 12809747
TI  - Predicting stuttering from linguistic factors for German speakers in two age
      groups.
AB  - Brown's factors [J. Speech Disorders 10 (1945) 181] predict the likely loci of
      disfluency in English-speaking adults who stutter. A word is more likely to be
      stuttered for these speakers if it is a content word, starts with a consonant, is
      positioned at the beginning of a sentence, and if it is a long word. These same
      factors were examined in native German-speaking children and adults who stutter.
      Speech data of 15 German adults and 17 children were coded according to Brown's
      factors. For the adult group, it was predicted that words starting with
      consonants would not lead to as much of an increase in disfluencies compared with
      English samples, because of cross-linguistic differences in syllable onset
      properties. It was predicted that stuttering would be more likely in later
      sentence positions in German because in German the verb is usually near the end
      of a sentence. There were no obvious reasons to expect differences on the two
      remaining factors, content words and word length. With children, it was
      hypothesised that Brown's factors that specify level of linguistic difficulty
      would not be such a good predictor of stuttering rate. Specifically, it was
      predicted that the difference in stuttering rate between function and content
      words would be lower in children. For the adults both word type
      (content/function) and word length increased stuttering rate significantly,
      whereas changes in stuttering rate for the other two factors were non
      significant. It was also found that when word difficulty (based on a combined
      measure of all factors) increased, stuttering rate rose. With children, only the
      word-length factor was significant, and stuttering rate was not governed to the
      same extent by overall word difficulty. Conclusions are drawn as to the effect of
      linguistic and motor influences on stuttering. EDUCATIONAL OBJECTIVES: The reader
      will learn about and be able to describe: (1) how linguistic factors affect
      stuttering rates in German; (2) the different patterns of adults and children who
      stutter and how language might influence this pattern; and (3) how to interpret
      these findings in light of a current theory of fluency failure.

PMID- 12809748
TI  - Childhood stuttering and speech disfluencies in relation to children's mean
      length of utterance: a preliminary study.
AB  - The purpose of this study was to examine the influence of utterance length and
      complexity relative to the children's mean length of utterance (MLU) on
      stuttering-like disfluencies (SLDs) for children who stutter (CWS) and
      nonstuttering-like disfluencies (nonSLDs) for children who do not stutter (CWNS).
      Participants were 12 (3;1-5;11, years;months) children: 6 CWS and 6 age-matched
      (+/-5 months) CWNS, with equal numbers in each talker group (CWS and CWNS)
      exhibiting MLU from the lower to the upper end of normal limits. Data were based
      on audio-video recordings of each child in two separate settings (i.e., home and
      laboratory) during loosely structured, 30-min parent-child conversational
      interactions and analyzed in terms of each participant's utterance length, MLU,
      frequency and type of speech disfluency. Results indicate that utterances above
      children's MLU are more apt to be stuttered or disfluent and that both stuttering
      like as well as nonstuttering-like disfluencies are most apt to occur on
      utterances that are both long and complex. Findings were taken to support the
      hypothesis that the relative "match" or "mismatch" between linguistic components
      of an utterance (i.e., utterance length and complexity) and a child's language
      proficiency (i.e., MLU) influences the frequency of the child's stuttering/speech
      disfluency. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to:
      (1) compare different procedures for assessing the relationship among stuttering,
      length and complexity of utterance, (2) describe the difference between relative
      and absolute measures of utterance length, (3) discuss the measurement and value
      of mean length of utterance and its possible contributions to childhood
      stuttering, and (4) describe how length and complexity influence nonstuttering
      like disfluencies of children who stutter as well as the stuttering-like
      disfluencies of children who do not stutter.

PMID- 12809749
TI  - A preliminary study of self-esteem, stigma, and disclosure in adolescents who
      stutter.
AB  - This study examined the self-esteem, perceived stigma, and disclosure practices
      of 48 adolescents who stutter divided into two age cohorts: younger (13, 14, and
      15 years) and older (16, 17, and 18 years) adolescents. Results revealed that 41
      (85%) of the participants scored within 1 S.D. from the mean on a standardized
      measure of self-esteem, indicative of positive self-esteem. Results also showed
      that stuttering did not present a stigmatizing condition for the majority (65%)
      of adolescents who stutter. However, 60% of participants indicated that they
      "rarely" or "never" discussed their stuttering. The younger adolescents perceived
      stuttering as a more negative and stigmatizing condition than older adolescents.
      Implications for understanding stuttering in adolescents are discussed.
      EDUCATIONAL OBJECTIVES: Readers will learn about and understand (a) the role of
      stigma, disclosure, and self-esteem in stuttering; (b) the methods used to
      evaluate stigma, disclosure, and self-esteem in adolescents; and (c) the
      similarities between adolescents who stutter and normative data on self-esteem
      and stigma scales.

PMID- 12809750
TI  - In vitro and in vivo efficacy of alpha-cyclodextrin for treatment of experimental
      cryptosporidiosis.
AB  - The efficacy of alpha-cyclodextrin against infection by Cryptosporidium parvum
      was evaluated using in vitro and in vivo models. Cyclodextrins are water-soluble
      cyclic hexamers of glucose units with hydrophobic cavities capable of
      solubilizing lipophiles and are widely used as drug excipients in the
      pharmaceutical industry. The viability of purified C. parvum oocysts, exposed for
      30, 60, 90, 120 min and 24h to different concentrations of alpha-cyclodextrin
      (2.5, 5, 7.5, 10, 12.5 and 15%), was evaluated by inclusion or exclusion of two
      fluorogenic vital dyes and by an excystation technique. Preventive and curative
      efficacies against cryptosporidial infections, at different doses (2.5 and 5%)
      and regimes of administration of alpha-cyclodextrin, were determined in an
      experimental neonatal mice model. Results of the viability assay showed a
      decrease in oocyst viability that was associated with an increase in exposure
      time, for each of the concentrations used. Moreover, a high proportion of
      nonviable oocysts (81%) was observed when C. parvum oocysts were exposed to alpha
      cyclodextrin (2.5%) for 24h. The intensity of infection, determined 7 days post
      inoculation by examination of intestinal homogenates, was significantly lower
      (P<0.05) than in the control litters, for all the assays carried out with alpha
      cyclodextrin. Only 38.8% of the animals became infected when the alpha
      cyclodextrin solution (5%) was administered 2h before inoculated oocysts, and
      every 24h at 1 and 2 days post-inoculation.

PMID- 12809751
TI  - Serological evidence of Neospora caninum infections in beef bulls in six counties
      of the Corrientes province, Argentina.
AB  - The purpose of the present work was to identify Neospora caninum infections in
      beef bulls belonging to 19 herds from six counties located in the Corrientes
      province, Argentina. The presence of antibodies to N. caninum was evaluated in
      305 serum samples of bulls (Bos taurus and Bos indicus). Age and breed were
      recorded. An indirect fluorescent antibody test was used to determine specific
      antibodies. The number of bulls with natural Neospora-infection was 15 of 305
      (4.9%). No association between serologic status and breed (odds ratio (OR), 0.53;
      95% CI, 0.18-1.53) was found. Neospora-infected beef bulls were identified in the
      present work. The bull role in bovine neosporosis and the risk of horizontal
      transmission for cows should be investigated.

PMID- 12809752
TI  - Humoral immunity and reinfection resistance in dogs experimentally inoculated
      with Babesia canis and either treated or untreated with imidocarb dipropionate.
AB  - It is proposed that the chronic asymptomatic carrier state produced by Babesia
      canis infection could make dogs more resistant against subsequent infections.
      This suggests that treatment with imidocarb dipropionate, which removes the
      organism, can make dogs more susceptible to reinfection in a short period of
      time. Ten male and female dogs of approximately 4-5 months of age were inoculated
      with B. canis. Half of them received treatment with imidocarb dipropionate (7
      mg/kg) on days 15 and 27 post-infection and the other half were untreated. All
      the animals were examined using clinical and laboratory methods (CBC, platelet
      counts and serological study by indirect immunofluorescence test) for a 6-month
      period. Antibodies were first detected on day 7 post-injection and remained at
      high levels (1:2560) over the period in the non-treated group. This result was
      significantly different (P<0.001) from the treated group in which antibodies
      titers declined after day 34 post-infection. Six months later, after a homologous
      challenge infection only the dogs of treated group showed parasitaemia,
      thrombocytopenia and splenomegaly, which was significantly different (P<0.05)
      from the non-treated group. The sterilizing treatment with imidocarb dipropionate
      was effective in clearing the infection, but inhibited the maintenance of
      protective antibodies, making the animals more susceptible to reinfection.

PMID- 12809753
TI  - Productivity effects of bovine mange and control with ivermectin.
AB  - A randomised block design study was conducted to evaluate the effects of mange on
      cattle. Twenty-four Simmentaler Fleckvieh bulls were formed into eight replicates
      of three bulls based on Day -56 body weight (288-414 kg). Within replicates bulls
      were randomly allocated to groups G1: uninfested control, G2: infested control or
      G3: infested, treated with 0.2mg ivermectin/kg (1% ivermectin injection; IVOMEC,
      Merial) on Day 0. The G2 and G3 bulls were infested with Sarcoptes/Chorioptes
      mites on Days -56 and -49. Feed consumption was recorded daily throughout the
      study (Days -56 to 56). Body weights were measured and serum samples collected.
      Mites were counted at bi-weekly intervals from Day -14 on. The carcasses of the
      bulls and the leather produced from their hides were evaluated. Differences
      between variables were declared significant if P</=0.05. All G2 and G3 bulls
      became infested. No Sarcoptes or Chorioptes mites were detected on the G3 bulls
      after Day 14 or Day 28, respectively, whereas G2 bulls maintained infestation
      throughout the study. From Days -42 to 0, anti-Sarcoptes antibody levels in the
      two infested groups increased linearly, while levels in the uninfested G1
      remained near zero. From Day 14 to Day 56, antibody levels in G2 continued to
      increase and those in G3 decreased (P</=0.05). From Days -56 to 0, G1 had
      significantly greater mean weight gain (94.0 kg) than the infested G2 and G3
      (76.1 and 75.9 kg). During Days 0-56, G3 gained significantly more weight (90.4
      kg) than G2 (58.8 kg), while G1 gained 76.0 kg, not significantly different from
      either G2 or G3. During Days -56 to 0, the feed conversion efficiency (kg gain/kg
      feed) of the infested G2 and G3 was significantly lower than that of the
      uninfested G1; during the 56 days following treatment, feed conversion efficiency
      of G3 was significantly higher than that of G2, while the uninfested G1 was
      intermediate. Carcass weight of G2 was significantly lower than those of G1 and
      G3, which did not differ significantly. Carcass yield, rib eye area and weight of
      kidney fat of the uninfested G1 were significantly greater than those of G2 and
      G3. Weights of the adrenal glands, prescapular and precrural lymph nodes were
      significantly higher for the infested G2 than for the other two groups.
      Significantly less of leather area from the infested G2 was of usable quality
      than of the leathers from the uninfested G1 or the infested, treated G3, and the
      leathers from G2 showed significantly more severe gouging or etching than
      leathers from the two other groups.

PMID- 12809754
TI  - Evaluation of the enzyme-linked immunoelectrotransfer blot (EITB) for ovine
      hydatidosis relative to age and cyst characteristics in naturally infected sheep.
AB  - An enzyme-linked immunoelectrotransfer blot (EITB) for ovine echinococcosis was
      evaluated in an endemic area of the Peruvian central sierra. An overall test
      sensitivity of 91.4% was determined for 199 sheep. EITB sensitivity reached a
      plateau of nearly 100% at 3 years of age, while the prevalence of cystic disease
      peaked at 95% in sheep >/=6 years of age. In this highly endemic area, 61.7% of
      sheep without detectable cystic disease at necropsy (n=47) had positive EITB
      results. Relationships between EITB sensitivity, age, and cyst location, size,
      number, type, fertility, and viability were evaluated with logistic regression
      models. EITB sensitivity increased 14-fold in sheep with calcified cysts and 4
      fold for each 1cm increase in pulmonary cyst size.

PMID- 12809755
TI  - Dose confirmation of moxidectin 0.5% pour-on against adults and fourth-stage
      larvae of various Cooperia spp. and Trichostrongylus colubriformis in Louisiana.
AB  - Thirty-five castrate or intact Holstein male calves, ranging in weight from 122
      to 210kg, were used in the study. On study Days -15 and -14, all study calves
      were treated with fenbendazole 10% paste at 10mg/kg to remove existing nematode
      infections. All cattle had zero egg counts on Day -1. Experimental infections of
      a mixed species inoculum were administered to all calves on Day 0. The inoculum
      consisted of Cooperia spp. (primarily C. punctata, but also C. pectinata, C.
      spatulata, C. oncophora and C. surnabada-total 40,961); Ostertagia ostertagi
      1550; Trichostrongylus colubriformis-4996; and Oesophagostomum radiatum-38.
      Necropsy results from two of three monitor calves slaughtered on Day 6 after
      infection indicated that Day 6 was an appropriate time to evaluate efficacy of
      moxidectin against fourth larval stages (L(4)). The remaining 32 calves were
      randomly allotted to four groups of eight based on body weights. Eight calves
      (Group 1) were treated with moxidectin 0.5% pour-on at 0.5mg/kg on Day 6 to
      evaluate efficacy against nematode larval stages; eight control calves (Group 2)
      were matched with these principals. Eight calves (Group 3) were also treated with
      moxidectin pour-on at the same dosage on Day 23 in order to determine efficacy
      against adult nematodes; eight control calves (Group 4) were matched with these
      principals. In both cases, principals and controls of the Days 6 and 23
      treatments were necropsied at 14-15 days after treatment. C. punctata was the
      only species found in a sufficient number of controls to evaluate moxidectin
      efficacy against the L(4). Moxidectin pour-on was not effective (P<0.05) against
      C. punctata L(4) by arithmetic means, but was highly effective based on geometric
      means. Regardless of whether arithmetic or geometric means were used for percent
      efficacy calculations, moxidectin pour-on was demonstrated to be highly effective
      (>99%) against the adult stages of C. oncophora, C. punctata, C. spatulata, C.
      surnabada, Cooperia spp. adult females and T. colubriformis adults.

PMID- 12809756
TI  - Serine protease activity in excretory-secretory products of Oestrus ovis
      (Diptera: Oestridae) larvae.
AB  - The sheep bot fly, Oestrus ovis, is a very common myiasis of nasal and sinus
      cavities of sheep and goats causing severe welfare and production implications.
      As the viability of O. ovis adult flies strictly depends on larval abilities to
      assimilate and to stock nutrients from the host, it was necessary to investigate
      proteolytic activities in larval excretory/secretory products (ESP). ESP of O.
      ovis larvae degrade mucosal and plasmatic components such as mucin, albumin or
      immunoglobulin G. A preliminary biochemical characterization, using substrate gel
      analysis and inhibitor sensitivity, demonstrated the presence of at least six
      major serine proteases (molecular weights from 20 to 100 kDa), mainly trypsin
      like, secreted in the digestive tube of larvae. Their involvement in larval
      trophic activity and evasion from the host immune response is further discussed
      as O. ovis excretory/secretory serine proteases could represent potential
      vaccinal targets.

PMID- 12809757
TI  - Review of successes and failures of contagious bovine pleuropneumonia control
      strategies in Tanzania.
AB  - Contagious bovine pleuropneumonia (CBPP) was first introduced in Tanzania in 1916
      and was eradicated in 1964. The disease re-emerged in the country in 1990 and
      since then it has spread widely, threatening the entire national cattle herd.
      Because of lack of a clear disease-control policy, uncontrolled cattle movements,
      lack of public awareness and commitment, ineffective legislation, attempts to
      control and eradicate the disease for the last 10 years have failed. We reviewed
      the methods that were used to control CBPP in Tanzania during the 1916-1964 and
      1990 episodes.

PMID- 12809758
TI  - Maedi-visna impact on productivity in Quebec sheep flocks (Canada).
AB  - An epidemiological study was conducted to determine the impact of maedi-visna
      (MV) seropositivity on productivity in commercial sheep flocks of the province of
      Quebec, Canada. A total of 1734 ewes and 220 rams were selected randomly from 29
      flocks distributed in the Bas-St-Laurent and Estrie regions. Serostatus was
      determined with an enzyme-linked immunosorbent assay (ELISA) using recombinant
      proteins.Flock-specific, animal-level seroprevalence varied from 3 to 70%
      (median=29%). Seroprevalence increased with age and size of the flock, and was
      higher in ewes relative to rams (but was not associated with body score). A
      decrease of 0.94 kg per lamb in weaning weight was seen only for lambs raised by
      seropositive ewes >/=4 years old, and seropositivity in ewes of any age was
      associated with an increase in 0-30 days lamb-mortality (OR: 1.65). The impact of
      MV infection on weaning weight and lamb mortality did not vary between flocks,
      and seropositivity in ewes was not associated with litter size or lamb's birth
      weight.

PMID- 12809759
TI  - Biosecurity practices on intensive pig production systems in Chile.
AB  - Chile eradicated classical swine fever (CSF) in April 1998, following a 17-year
      eradication programme. The authors describe biosecurity levels of pig farms in
      Chile after the eradication of CSF. A formal survey was administered to 50 large
      integrated pig farms, which represented almost 60% of the swine population. The
      main topics on the questionnaire were production, health management, biosecurity,
      insurance and information about CSF outbreaks in the past. Biosecurity practices
      were analysed according to the criteria stated by Barcelo and Marco in 1998. A
      scoring system to measure biosecurity was designed and pig farms were classified
      according to this score. An adjusted specific measure is discussed as a potential
      indicator of risk for disease infections. The authors explore associations
      between biosecurity herd size and insurance policy against CSF.

PMID- 12809760
TI  - Social-network analysis of Mycobacterium bovis transmission among captive
      brushtail possums (Trichosurus vulpecula).
AB  - Wild brushtail possums (Trichosurus vulpecula) are the main source of
      Mycobacterium bovis infection for New Zealand livestock. The disease is spread
      principally by infectious aerosol; therefore, social interactions determine
      disease transmission. In captive possums, den-sharing behaviour provided the
      greatest risk of tuberculosis transmission between animals. Den sharing between
      individual possums was used as the basic measurement for quantifying close
      proximity between animals over extended periods. Social-network analysis (SNA)
      was used to model patterns of social behaviour and to predict tuberculosis
      transmission. There was great diversity between groups in their social behaviour
      but there were consistent trends in the SNA measures (closeness and flow
      betweenness). With time, the social distance between possums in the same group
      increased, the social network became more homogeneous and the possums less
      differentiated from each other. Alteration of the physical environment of the
      pens (such as changing the number of dens or relocating the group to a new pen)
      had an inconsistent effect on social structure when comparing different groups.
      During the infection-transmission study, the possums that became infected had
      greater closeness and flow-betweenness scores than those that remained free of
      infection. Although standard statistical descriptive measures (such as the number
      of partners and the frequency of den-sharing events) were greater for the
      infected than the infection-free possums, the SNA-specific measures were more
      precise and could be compared across time and between groups.

PMID- 12809761
TI  - The association between quarter somatic-cell counts and clinical mastitis in
      three British dairy herds.
AB  - The association between quarter somatic-cell counts (QSCCs) of milk and the risk
      of clinical mastitis (CM) was investigated in a 1-year study on three dairy herds
      in Somerset, UK. The three herds had 95-130 milking cows and an annual mean bulk
      milk somatic-cell count (BMSCC) of <150 x 10(3)cells/ml. The farms were visited
      every 4-6 weeks at morning milking when quarter-milk samples were collected. The
      farmers recorded all cases of CM and were trained to collect sterile milk samples
      from affected quarters, before treatment for bacteriology. The three herds had CM
      incidence rates of 25.4, 55.2, and 67.6 quarter-cases per 100 cow-years.
      Escherichia coli and Streptococcus uberis were cultured from approximately 50% of
      cases. QSCC was categorised and the risk of CM occurring in the month after the
      QSCC was examined using multilevel models to account for the correlated nature of
      the dependent data. Three models were developed: one for all cases of CM, one for
      those caused by coliforms and one for those caused by S. uberis. When all cases
      of CM were considered, quarters with somatic-cell count (SCC) 21-100 x
      10(3)cells/ml had reduced odds (OR=0.60, P=0.06) and quarters with SCC >200 x
      10(3)cells/ml has over three time the odds (OR=3.7, P<0.01) of CM compared with
      QSCC 1-20 x 10(3)cells/ml. When only coliform CM were investigated, quarters with
      SCC 6-200 x 10(3)cells/ml had reduced odds of coliform CM (OR=0.47, P=0.04)
      compared with QSCC 1-5 x 10(3)cells/ml, and SCC >200 x 10(3)cells/ml were not
      significantly different from the baseline. Finally, when S. uberis CM were
      investigated, quarters with SCC >200 x 10(3)cells/ml had more than three times
      the odds of S. uberis CM compared with QSCC 1-20 x 10(3)cells/ml (OR=3.73,
      P<0.01). QSCC <21 x 10(3) and >200 x 10(3)cells/ml are associated with increased
      odds of CM in the following 4-6 weeks; this association may be pathogen specific.

PMID- 12809762
TI  - Comments on "Pouillot, R., Gerbier, G., Gardner, I.A., 2002. "TAGS", a program
      for the evaluation of test accuracy in the absence of a gold standard. Prev. Vet.
      Med. 53, 67-81".

PMID- 12809764
TI  - Reply to letter to the editor: How effective is acute normovolaemic haemodilution
      in femoro-distal bypass surgery?

PMID- 12809765
TI  - Wear resistance of experimental Ti-Cu alloys.
AB  - After using cast titanium prostheses in clinical dental practice, severe wear of
      titanium teeth has been observed. This in vitro study evaluated the wear behavior
      of teeth made with several cast titanium alloys containing copper (CP Ti+3.0 wt%
      Cu; CP Ti+5.0 wt% Cu; Ti-6Al-4V +1.0 wt% Cu; Ti-6Al-4V+4.0 wt% Cu) and compared
      the results with those for commercially pure (CP) titanium, Ti-6Al-4V, and gold
      alloy. Wear testing was performed by repeatedly grinding upper and lower teeth
      under flowing water in an experimental testing apparatus. Wear resistance was
      assessed as volume loss (mm(3)) at 5kgf (grinding force) after 50,000 strokes.
      Greater wear was found for the six types of titanium than for the gold alloy. The
      wear resistance of the experimental CP Ti+Cu and Ti-6Al-4V+Cu alloys was better
      than that of CP titanium and Ti-6Al-4V, respectively. Although the gold alloy had
      the best wear property, the 4% Cu in Ti-6Al-4V alloy exhibited the best results
      among the titanium metals. Alloying with copper, which introduced the alpha
      Ti/Ti(2)Cu eutectoid, seemed to improve the wear resistance.

PMID- 12809766
TI  - Bioactive sol-gel glasses with and without a hydroxycarbonate apatite layer as
      substrates for osteoblast cell adhesion and proliferation.
AB  - The biocompatibility of three sol-gel bioactive glasses with SiO(2) as the main
      constituent (75, 72.5 and 70 mol%), identical CaO content (25mol%), and without
      or with P(2)O(5) as third constituent (0, 2.5 and 5 mol%), have been analyzed
      (S75, S72.5P2.5, and S70P5 glasses). These studies were performed on both
      untreated glasses and on glasses coated with a hydroxycarbonate apatite (HCA)
      layer formed in vitro by soaking 7d in an acellular simulated body fluid. Cell
      attachment, spreading and proliferation were studied using neonatal rat calvaria
      osteoblasts. Cells attach to the three untreated glasses but show a higher
      efficiency on that with the higher phosphate content (S70P5). The formation of
      the HCA layer significantly enhances this process (1.7-fold). In all cases,
      attachment is followed by cell spreading on the surface of the materials,
      adopting the cells a flattened morphology and showing diverse anchoring cell
      projections. Mitotic activity has been detected on osteoblasts growing on the sol
      gel glasses, being this process 2-4-fold higher when the apatite-like layer is
      already formed. Taking into account the results herein presented, these bioactive
      glasses can be considered biocompatible. In addition, their biocompatibility is
      greatly enhanced after induction of the formation of an HCA layer.

PMID- 12809767
TI  - Modulation of angiogenic functions in human macrophages by biomaterials.
AB  - We examined the ability of polyvinylchloride (PVC), polytetrafluorethylene (PTFE)
      and tissue culture polystyrene (TCPS) to affect angiogenic functions in human
      monocyte-derived macrophages by measuring the mRNA expression of genes encoding
      angiogenic and anti-angiogenic molecules including basic fibroblast growth factor
      (bFGF), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and
      thrombospondin-1 (Tsp-1). The angiogenic activity of the corresponding macrophage
      conditioned media (CM) was measured by the proliferation of endothelial cells and
      the sprouting of new capillaries from fragments of human placental blood vessels.
      We determined that bFGF was not expressed in macrophages while VEGF and Tsp-1
      mRNAs were expressed constitutively. Ang-1 was expressed in macrophages cultured
      up to 7 days on PTFE and TCPS independent of the culture stage. In contrast,
      macrophages cultured on PVC did not produce detectable amounts of Ang-1 mRNA
      after 7 days. CM from macrophages cultured either on PTFE or TCPS stimulated
      angiogenesis whereas CM from macrophages cultured on PVC inhibited it. The
      results demonstrate that polymers can cause differential expression of the
      angiogenic molecule Ang-1 in macrophages. They also induce different phenotypes
      of macrophages, which can either stimulate or inhibit angiogenesis suggesting a
      material-dependent influence on neovascularization.

PMID- 12809768
TI  - Micro- and nano-testing of calcium phosphate coatings produced by pulsed laser
      deposition.
AB  - Micro- and nano-testing methods have been explored to study the thin calcium
      phosphate coatings with high adhesive strength. The pulsed laser deposition (PLD)
      technique was utilised to produce calcium phosphate coatings on metal substrates,
      because this type of coatings exhibit much higher adhesive strength with
      substrates than conventional plasma-sprayed coatings. Due to the limitations of
      the conventional techniques to evaluate the mechanical properties of these thin
      coatings (1 microm thick), micro-scratch testing has been applied to evaluate the
      coating-to-substrate adhesion, and nano-indentation to determine the coating
      hardness and elastic modulus. The test results showed that the PLD produced
      amorphous and crystalline HA coatings are more ductile than titanium substrates,
      and the PLD coatings are not delaminated from the substrates by scratch. Also,
      the results showed that the crystalline HA coating is superior in internal
      cohesion to the amorphous one, even though the lower elastic modulus of amorphous
      coating could be more mechanically compatible with natural bone.

PMID- 12809770
TI  - Osteoblasts response to allogenic and xenogenic solvent dehydrated cancellous
      bone in vitro.
AB  - The present in vitro study investigates the cellular interaction of primary human
      osteoblasts with human and bovine solvent dehydrated cancellous bone (SDCB)
      discs. These are bio-implants from solvent dehydrated, gamma-irradiated preserved
      human and bovine cancellous bone, pre-treated to remove all cells, genetic
      components and water soluble proteins. Primary human osteoblasts were harvested
      from cancellous chips of trauma patients undergoing osteosynthesis with bone
      grafting from the iliac crest. All patients provided informed consent. The
      present investigation tested proliferation, synthesis of phenotypic marker, and
      morphology of primary cultured human osteoblasts on SDCB in vitro. The total
      protein and collagen type 1 content could not be revealed, due to the inherent
      naturally occurring protein content in these two bio-implants. In conclusion, our
      in vitro results suggest that SDCB may be a suitable bone substitute which
      provides a well structured and biocompatible scaffold for ingrowing human
      osteoblasts.

PMID- 12809769
TI  - A novel chemical modification of bioprosthetic tissues using L-arginine.
AB  - A novel chemical modification of biological tissues was developed by the direct
      coupling of bioactive molecule, L-arginine to bovine pericardium (BP). The
      modification involves pretreatment of BP using GA and followed by grafting
      arginine to BP by the reaction of residual aldehyde and amine group of L
      arginine. BP was modified by direct coupling of bioactive molecules and the
      effect of L-arginine coupling on calcification and biocompatibility was evaluated
      in vitro and in vivo. Modified BPs were characterized by measuring shrinkage
      temperature, mechanical properties, digestion resistance to collagenase enzyme,
      in vitro plasma protein adsorption and platelet adhesion, and in vivo
      calcification. Thermal and mechanical properties showed that the durability of
      arginine treated tissue increased as compared with fresh tissue and GA treated
      tissue. Resistance to collagenase digestion revealed that modified tissues have
      greater resistance to enzyme digestion than did fresh tissue and GA treated
      tissue. Lower protein adsorption and platelet adhesion were observed on modified
      tissue than non-modified tissue. In vivo calcification study demonstrated much
      less calcium deposition on arginine treated BP than GA treated one. Obtained
      results attest to the usefulness of L-arginine treated BP for cardiovascular
      bioprostheses.

PMID- 12809771
TI  - Nanoscale features influence epithelial cell morphology and cytokine production.
AB  - Available, easy and fast fabrication methods of nanostructured surfaces, and the
      knowledge that cells in vivo interacts with nanometer-sized structures/objects,
      led us to study the impact of nanotopography on cell morphology and cytokine
      production. Uroepithelial cells were seeded on three different substrate types:
      two with defined nanometer topographies and a flat control, all three having
      identical surface chemistry. The nanostructured substrates contained
      hemispherical pillars or step edges, the latter in the form of parallel grooves
      and ridges. Qualitative and quantitative analysis of cell morphology and cytokine
      production were studied. Both quantities were significantly different between
      cells cultured on hemispherically structured surfaces compared to flat control
      surfaces. Cells cultured on hemispherically structured surfaces showed a decrease
      in IL-6 and IL-8 production and were less spread, less round and more stellate
      (larger dispersion). Only cell morphology differed between cells cultured on
      grooved surfaces and flat control surfaces. These findings suggest that
      epithelial cell morphology and cytokine production are dependent on the
      underlying nanotopography.

PMID- 12809772
TI  - Photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2
      stimulates wound healing in healing-impaired db/db mice.
AB  - Application of ultraviolet light (UV-) irradiation to a photocrosslinkable
      chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2)
      resulted within 30s in an insoluble, flexible hydrogel. About 20% of the FGF
      2molecules were released from the FGF-2-incorporated chitosan hydrogel into
      phosphate buffered saline (PBS) within 1 day, after which no further significant
      release occurred under in vitro non-degradation conditions of the hydrogel. The
      FGF-2molecules retained in the chitosan hydrogel remained biologically active,
      and were released from the chitosan hydrogel upon the in vivo biodegradation of
      the hydrogel. In order to evaluate its accelerating effect on wound healing, full
      thickness skin incisions were made on the back of healing-impaired diabetic
      (db/db) mice and their normal (db/+) littermates. Application of the chitosan
      hydrogel significantly induced wound contraction and accelerated wound closure in
      both db/db and db/+ mice. However, the addition of FGF-2 in the chitosan hydrogel
      further accelerated wound closure in db/db mice, although not in db/+ mice.
      Histological examination also has demonstrated an advanced granulation tissue
      formation, capillary formation and epithelialization in wounds treated with FGF-2
      incorporated chitosan hydrogels in db/db mice.

PMID- 12809773
TI  - Repair of segmental long bone defect in rabbit femur using bioactive titanium
      cylindrical mesh cage.
AB  - A segmental rabbit femur defect was repaired using an empty bioactive titanium
      (BAT) mesh cage. A 10mm long titanium mesh cage was positioned in the bony defect
      and reinforced by intramedullary fixation. The BAT surface was prepared by
      chemical and thermal treatment. Pure titanium cages were used as a control.
      Torsional stiffness of the BAT group at 4 weeks was approximately equal to, and
      at 8 weeks twice, that of the intact femur. Differences between the torsional
      stiffness of the control and BAT groups were significant at both time intervals.
      Histological examinations showed that woven bone appeared around the cage by 4
      weeks and transformed to lamella bone by 8 weeks. New bone bonded to the BAT
      surface without an intervening layer. The BAT cage enhanced the bone repairing
      process and achieved faster repair of long bone segmental defects.

PMID- 12809774
TI  - Cellular interactions and degradation of aliphatic poly(ester amide)s derived
      from glycine and/or 4-amino butyric acid.
AB  - A series of poly(ester amide)s derived from amino acid (glycine or 4-amino
      butyric acid), diol (1,6-hexanediol or 1,4-butanediol) and sebacoyl chloride were
      prepared by interfacial polymerization. FT-IR analysis indicated that for
      poly(ester amide)s derived from glycine, only amide-amide hydrogen bonds and
      hydrogen-bonded C=O ester groups were established, whereas the poly(ester amide)s
      derived from 4-amino butyric acid contained amide-amide hydrogen bonds and amide
      ester hydrogen bonds, including NH groups and C=O ester groups in free state. The
      biodegradability was estimated by weight residue of poly(ester amide) films in pH
      6 buffer solution with papain at 37 degrees C. The poly(ester amide) films
      derived from glycine demonstrated significantly improved degradability compared
      to the poly(ester amide) films derived from 4-amino butyric acid. This difference
      of degradation rate could be explained by the bonding state in C=O ester groups.
      The cellular interaction of the poly(ester amide)s was studied by measuring the
      proliferation of human dermal fibroblasts on the polymer films. The cells
      proliferated significantly faster on poly(ester amide) films derived from 4-amino
      butyric acid than on poly(ester amide) films derived from glycine. These results
      suggest that the poly(ester amide) prepared in this study may serve as a
      potential cell-compatible biomedical material.

PMID- 12809775
TI  - Compositional changes of a dicalcium phosphate dihydrate cement after
      implantation in sheep.
AB  - A hydraulic calcium phosphate cement having dicalcium phosphate dihydrate (DCPD)
      as end-product of the setting reaction was implanted in a cylindrical defect in
      the diaphysis of sheep for up to 6 months. The composition of the cement was
      investigated as a function of time. After setting, the cement composition
      consisted essentially of a mixture of DCPD and beta-tricalcium phosphate (beta
      TCP). In the first few weeks of implantation, the edges of the cement samples
      became depleted in DCPD, suggesting a selective dissolution of DCPD, possibly due
      to low pH conditions. The cement resorption at this stage was high. After 8
      weeks, the resorption rate slowed down. Simultaneously, a change of the color and
      density of the cement center was observed. These changes were due to the
      conversion of DCPD into a poorly crystalline apatite. Precipitation started after
      6-8 weeks and progressed rapidly. At 9 weeks, the colored central zone reached
      its maximal size. The fraction of beta-TCP in the cement was constant at all
      time. Therefore, this study demonstrates that the resorption rate of DCPD cement
      is more pronounced as long as DCPD is not transformed in vivo.

PMID- 12809776
TI  - Evaluation of sodium alginate for bone marrow cell tissue engineering.
AB  - Sodium alginate has applications as a material for the encapsulation and
      immobilisation of a variety of cell types for immunoisolatory and biochemical
      processing applications. It forms a biodegradable gel when crosslinked with
      calcium ions and it has been exploited in cartilage tissue engineering since
      chondrocytes do not dedifferentiate when immobilised in it. Despite its
      attractive properties of degradability, ease of processing and cell
      immobilisation, there is little work demonstrating the efficacy of alginate gel
      as a substrate for cell proliferation, except when RGD is modified. In this study
      we investigated the ability of rat bone marrow cells to proliferate and
      differentiate on alginates of differing composition and purity. The mechanical
      properties of the gels were investigated. It was found that high purity and high
      G-type alginate retained 27% of its initial strength after 12 days in culture and
      that comparable levels of proliferation were observed on this material and tissue
      culture plastic. Depending on composition, calcium crosslinked alginate can act
      as a substrate for rat marrow cell proliferation and has potential for use as 3D
      degradable scaffold.

PMID- 12809777
TI  - Characterization and performance of membranes designed for
      macroencapsulation/implantation of pancreatic islet cells.
AB  - Amphiphilic polymer membranes were synthesized for macroencapsulation of cells
      and characterized by select chemical and biological techniques. The membranes
      were prepared by crosslinking hydrophilic poly(N,N-dimethyl acrylamide) (PDMAAm)
      main chains with hydrophobic di-, tri-, and octa-methacrylate telechelic
      polyisobutylene (PIB) stars. The hydrophilic/hydrophobic composition and the
      molecular weights between crosslink sites (both M(c,hydrophilic) and
      M(c,hydrophobic)) were controlled by synthesis conditions. Small tubular
      membranes were made by in situ rotational copolymerization/crosslinking and
      filled with pancreatic rat islets. The water-swelling behavior, mechanical
      properties, and oxygen and insulin diffusion were studied. Macroencapsulatory
      performance of these membranes was investigated in vitro by macroencapsulation of
      pancreatic rat islets within tubular membranes for up to 1.5 months, and studying
      the insulin secreting ability of encapsulated islets in culture. The membranes
      are robust and maintain their integrity for the period of encapsulation. They
      allow oxygen and insulin diffusion. Macroencapsulated islets maintained their
      viability and insulin secretion over an extended period (i.e., 45 days).

PMID- 12809778
TI  - Synthesis, permeability and biocompatibility of tricomponent membranes containing
      polyethylene glycol, polydimethylsiloxane and polypentamethylcyclopentasiloxane
      domains.
AB  - The synthesis of "smart" tricomponent amphiphilic membranes containing
      poly(ethylene glycol) (PEG), polydimethylsiloxane (PDMS) and
      polypentamethylcyclopentasiloxane (PD(5)) domains is described. Contact angle
      hysteresis indicates that in air, the surfaces of such PEG/PD(5)/PDMS membranes
      are enriched by the hydrophobic components, PDMS and PD(5), while in water, the
      surfaces are rich in the hydrophilic PEG. The oxygen permeability of a series of
      membranes with varying M(c,hydrophilic) (M(n,PEG)=4600, 10,000 and 20,000 g/mol)
      and varying PEG/PD(5)/PDMS compositions was studied. Oxygen permeability
      increased with the amount of PDMS in the membrane. The molecular weight cut-off
      (MWCO) ranges and permeability coefficients of insulin through a series of
      PEG/PD(5)/PDMS(=29/14/57) membranes with varying M(c,hydrophilic) were
      determined. Insulin permeability is directly related to M(c,hydrophilic) of the
      membrane. MWCO studies show that the membranes are semipermeable to, i.e., allow
      the transport of smaller proteins such as insulin (M(n)=5733 g/mol, R(s)=1.34 nm)
      and cytochrome c (M(n)=12,400 g/mol, R(s)=1.63 nm), but are barriers to larger
      proteins such as albumin (M(n)=66,000 g/mol, R(s)=3.62 nm). Implantation of
      representative membranes in rats showed them to be biocompatible. According to
      these studies, PEG/PD(5)/PDMS membranes may be suitable for biological
      applications, e.g., immunoisolation of cells.

PMID- 12809779
TI  - Electrophoretic deposition of porous hydroxyapatite scaffold.
AB  - Bioactive porous hydroxyapatite (HA) scaffold was fabricated using
      electrophoretic deposition (EPD) technique in the present work. Bulk HA scaffold
      was achieved by repeated deposition. The green scaffold was sintered at 1200
      degrees C to 82% of the theoretical density. Scanning electron microscopy
      examination and mercury porosimetry measurement have shown that the porosity
      remains interconnected and a range of pore size from several microns to hundreds
      of microns was obtained. X-ray diffraction analysis was performed and confirmed
      that there is no HA decomposition during the sintering process. Mechanical
      characterization has also shown that the EPD scaffold possesses excellent
      properties. Cell culturing experiment was carried out and the result shows that
      the scaffold bioactivity is not only dependent on the interconnectivity of the
      pores, but also the pore size.

PMID- 12809780
TI  - Rat costochondral cell characteristics on poly (L-lactide-co-epsilon
      caprolactone) scaffolds.
AB  - This study was designed to examine the adhesion, proliferation, and morphology of
      chondrocytes on new scaffolds; and to examine these cells histologically for the
      ability of the chondrocytes to maintain chondrogenic properties after
      subcutaneous implantation into nude mice. Both 75:25 poly (L-lactide-co-epsilon
      caprolactone) (75PLC) and 50:50 poly (L-lactide-co-epsilon-capro-lactone)
      scaffold (50PLC) were tested as a scaffold for rat costochondral resting zone
      chondrocytes in comparison with a type I collagen sponge scaffold (collagen
      scaffold). Both of the poly (L-lactide-co-epsilon-caprolactone) scaffolds (75PLC
      and 50PLC) were coated with type I collagen solution and the effects of the
      collagen coat (hybrid-PLC) were also examined. The hybrid-75PLC bound the same
      number of cells as the collagen scaffold, whereas the 75PLC and the 50PLC bound
      60% and 50% fewer cells than the collagen scaffold, respectively. The cell growth
      on the scaffolds progressed with culture time in all scaffolds. Cell morphology
      was assessed by scanning electron microscopy for differences in the structure of
      cellular interaction. Chondrocytes on every scaffold maintained a spherical
      shape. The hybrid-PLCs were superior to the PLCs with respect to the number of
      cells attached. The PLCs had an advantageous degradation characteristic in that
      they retained their original shape better than the collagen scaffold.
      Additionally, in the PLCs seeded, the cells retained their integrity 4 weeks
      after implantation, although the volume of collagen scaffold decreased by 50%.

PMID- 12809781
TI  - Endothelial cells grown on thin polyelectrolyte mutlilayered films: an evaluation
      of a new versatile surface modification.
AB  - Endothelial cell seeding constitutes an appreciated method to improve blood
      compatibility of small-diameter vascular grafts. In this study, we report the
      development of a simple innovative technique based on multilayered
      polyelectrolyte films as cell adhesive substrates. Polyelectrolyte multilayered
      films ending by poly(sodium-4-styrenesulfonate)/poly(allylamine hydrochloride)
      (PSS/PAH) or poly(L-glutamic acid)/poly(D-lysine) (PGA/PDL) could enhance cell
      adhesion by modification of the physico-chemical properties of the surface. The
      biological responses of human umbilical vein endothelial cells seeded on the
      polyelectrolyte multilayer films, on PDL or PAH monolayers, and on control
      surfaces, were evaluated in terms of initial attachment, growth, cellular
      metabolic activity, endothelial phenotype, and adhesion. The results showed that
      polyelectrolyte multilayers neither induce cytotoxic effects nor alter the
      phenotype of the endothelial cells. The polyelectrolyte multilayered films
      enhanced initial cell attachment as compared to the polyelectrolyte monolayer.
      Cell growth observed on the films was similar to that on TCPS. Among the
      different coating tested, the film ending by PSS/PAH exhibited an excellent
      cellular biocompatibility and appeared to be the most interesting surface in
      terms of cellular adhesion and growth. Such films could be used to cover
      hydrophobic (cell resistant) substrates in order to promote cell colonization,
      thereby constituting an excellent material for endothelial cell seeding.

PMID- 12809782
TI  - Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the
      intervertebral disc: a potential therapeutic model for disc degeneration.
AB  - Intervertebral disc degeneration is considered to be one of the major causes of
      low back pain. Despite this irreversible phenomenon, attempts to decelerate disc
      degeneration using various techniques have been reported. However, to date there
      has been no proven technique effective for broad clinical application. Based on
      previous studies, we hypothesize that maintenance of proteoglycan content in the
      disc is achieved by avoiding the depletion of nucleus pulposus and preserving the
      structure of the annulus is a primary factor in decelerating disc degeneration.
      One novel approach to solve the dilemma of intervertebral disc degeneration is
      found at the stem cell level. Mesenchymal stem cells (MSCs) are known to possess
      the ability to differentiate into various kinds of cells from mesenchymal origin.
      Although the majority of cells that contribute to disc formation are known to
      obtain chondrocyte-like phenotypes, no reported study has emphasized the
      correlation with mesenchymal stem cells. To evaluate the possible potential of
      MSCs in disc cell research and treatment of degenerative disc disease, autologous
      MSCs embedded in Atelocollagen gel were transplanted into the discs of rabbits
      which had undergone a procedure proven to induce degeneration. The results
      suggest that MSC transplantation is effective in decelerating disc degeneration
      in experimental models and provided new hopes for treatment of degenerative disc
      disease in humans. Atelocollagen gel served as an important carrier of MSCs in
      transplantation, permitting proliferation, matrix synthesis and differentiation
      of MSCs. This study strengthens the viable efficacy of practical application of
      MSCs in treatment of intervertebral disc disease.

PMID- 12809783
TI  - Thermal and photochemical nitric oxide release from S-nitrosothiols incorporated
      in Pluronic F127 gel: potential uses for local and controlled nitric oxide
      release.
AB  - The local delivery of nitric oxide (nitrogen monoxide, NO) by thermal or
      photochemical means to target cells or organs has a great potential in several
      biomedical applications, especially if the NO donors are incorporated into non
      toxic viscous matrices. In this work, we have shown that the NO donors S
      nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) can be
      incorporated into F127 hydrogels, from where NO can be released thermally or
      photochemically (with lambda(irr)>480nm). High sensitivity differential scanning
      calorimetry (HSDSC) and a new spectrophotometric method, were used to
      characterize the micellization and the reversal thermal gelation processes of the
      F127 hydrogels containing NO donors, and to modulate the gelation temperatures to
      the range 29-32 degrees C. Spectral monitoring of the S-NO bond cleavage showed
      that the initial rates of thermal and photochemical NO release (ranging from 2 to
      45 micromoll(-1)min(-1)) are decreased in the hydrogel matrices, relative to
      those obtained in aqueous solutions. This stabilization effect was assigned to a
      cage recombination mechanism and offers an additional advantage for the storage
      and handling of S-nitrosothiols. These results indicate that F127 hydrogels might
      be used for the thermal and photochemical delivery of NO from S-nitrosothiols to
      target areas in biomedical applications.

PMID- 12809784
TI  - Synthesis and characterization of biodegradable polylactide-grafted dextran and
      its application as compatilizer.
AB  - Brush-like biodegradable polylactide-grafted dextran copolymer (PLA-g-dextran)
      was by a bulk polymerization reaction using a trimethylsilyl-protected (TMS)
      dextran as macroinitiator and stannous octoate as catalyst. After the
      polymerization, the TMS groups could be easily removed by immersing the copolymer
      in methanol for 48 h. The PLA-g-dextran copolymers were characterized by (1)H
      NMR, GPC and intrinsic viscosity measurements. Besides, mouse 3T3 fibroblasts
      were cultured on these copolymeric substrates together with pure polylactide
      (PLA). Although the copolymers exhibited better hydrophilicity and cell affinity
      compared to pure PLA because of the incorporation of glucose units and the brush
      like architecture, it was found that the cells still could not migrate into the
      center part of scaffold made of PLA-g-dextran copolymer. In result, PLA-g-dextran
      copolymers themselves were not an appropriate choice for the cell scaffold
      material, however, it could be used as compatilizer to ameliorate the
      compatibility between hydrophilic dextran and hydrophobic PLA due to its
      amphiphilic structure, which could improve the mechanical properties of
      PLA/dextran blends by reducing the phase separation between PLA and dextran.
      Therefore, the PLA/dextran blends, which had good cell affinity and moderate
      mechanical strength, might be prospect cell scaffold materials.

PMID- 12809785
TI  - Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) block copolymers:
      characterization and their use as drug carriers for a controlled delivery system.
AB  - Poly(epsilon-caprolactone)-poly(ethylene glycol) (PECL) copolymers were
      synthesized from polyethylene glycol (PEG) and epsilon-caprolactone (epsilon-CL)
      using stannous octoate as catalyst at 160 degrees C by bulk polymerization. The
      effect of the molecular weight of PEG and the copolymer ratio on the properties
      of the copolymers was investigated by (1)H-NMR, IR, DSC and GPC. PCL and PECL
      microspheres containing human serum albumin were elaborated by solvent extraction
      method based on the formation of double w/o/w emulsion. Microspheres were
      characterized in terms of morphology, size, loading efficiency, and the
      efficiency of microspheres formation. The results show that the microspheres
      prepared from PECL-10 and PECL-15 copolymers achieved the highest loading
      efficiency (about 50%) among all copolymers. These results indicate that the
      properties of copolymers could be tailored by adjusting polymer composition. It
      is suggested that these matrix polymers may be optimized as carriers in the
      protein (antigen) delivery system for different purposes.

PMID- 12809786
TI  - Evaluation of anhydride oligomers within polymer microsphere blends and their
      impact on bioadhesion and drug delivery in vitro.
AB  - The effect of the addition of small molecular weight anhydride oligomers to
      polymer microspheres was evaluated and increased bioadhesion of the composite was
      demonstrated. Blends of low molecular weight anhydride oligomers with
      thermoplastic poly(fumaric-co-sebacic anhydride) [p(FASA)] and polycaprolactone
      were examined. The effects of anhydride oligomers on polymer microsphere
      degradation, crystallinity, and surface morphology were also explored. The
      results demonstrated that fumaric anhydride oligomer remained within polymer
      microspheres for several hours after exposure to phosphate buffer, formed a
      homogenous crystalline blend, increased bioadhesion as measured on rat intestine,
      and enhanced drug delivery in vitro as measured by the everted sac technique.

PMID- 12809787
TI  - Ion release from NiTi orthodontic wires in artificial saliva with various
      acidities.
AB  - NiTi orthodontic wire products from different manufacturers would have different
      corrosion resistance. We assayed the corrosion resistance, in terms of ion
      release, of different NiTi orthodontic wires in artificial saliva with various
      acidities. Four types of as-received commercial NiTi orthodontic wires were
      immersed in artificial saliva (37 degrees C) at pH 2.5-6.25 for different periods
      (1-28d). The amount of Ni and Ti ions released from NiTi wires was determined
      using an atomic adsorption spectrophotometer. Surface morphology and roughness of
      wires were related to the corrosion resistance. Results showed that the
      manufacturer, pH value, and immersion period, respectively, had a significantly
      statistical influence on the release amount of Ni and Ti ions. The amount of Ni
      ions released in all test solutions was well below the critical value necessary
      to induce allergy and below daily dietary intake level. The amount of Ti ions
      released in pH>/=3.75 solution was mostly not detectable, representing that the
      TiO(2) film on NiTi wires exhibited a good protection against corrosion. Pre
      existed surface defects on NiTi wires might be the preferred locations for
      corrosion. The NiTi wire with the highest release amount of metal ions had the
      maximal increase in surface roughness after immersion test, while a rougher
      surface did not correspond to a higher metal ion release.

PMID- 12809788
TI  - The effect of different power densities and method of exposure on the marginal
      adaptation of four light-cured dental restorative materials.
AB  - PURPOSE: To determine whether marginal adhesion is sensitive to different
      irradiation parameters, we investigated the in vitro adhesion values of four
      dental resins on metal surfaces. METHODS: Four groups of eight specimens each of
      Z250, Filtek flow, Dyract AP and Dyract flow were placed in pre-treated stainless
      steel cavities and irradiated using different methods of exposure. The curing
      lights used were a Spectrum 800 halogen curing light at settings of 800 and 450
      mW/cm(2) and an Optilux 501 ramping light. The maximum amount of push-out force
      required to displace the resin from the metal cavity was equated with adhesive
      value (shear bond strength). Comparisons (ANOVA, p<0.0001) were made within the
      same material and between the different materials when using different curing
      protocols. RESULTS: Significant lower bond strengths were recorded when curing
      was done by gradually increasing the intensity (ramping method) compared to
      curing with the fixed intensities (p>0.0001) Comparing the fixed intensities,
      significant lower bond strength values were obtained at 800 mW/cm(2) compared to
      450 mW/cm(2) (p<0.0001). For all exposures, the two flowable materials
      demonstrated weaker values when compared to the higher filled materials. CLINICAL
      SIGNIFICANCE: The advantage of initial slow polymerization (more elasticity and
      less tension) obtained by the so-called "soft start" method, was offset by a rise
      in total polymerization shrinkage, when final curing was completed at 1130
      mW/cm(2). These tests demonstrated that using halogen units, exposure for 40s
      with an intensity of 450 mW/cm(2) appeared to be the most promising for light
      curing dental resin composites.

PMID- 12809789
TI  - Platelet compatible blood filtration fabrics using a phosphorylcholine polymer
      having high surface mobility.
AB  - To obtain a novel polymer for coating on blood filtration devices, which can
      reduce platelet adhesion and activation when the polymer is in contact with blood
      under a dry condition, a phosphorylcholine polymer with high mobility of the
      polymer side chain was designed. The polymer possesses 2
      methacryloyloxyethoxyethyl phosphorylcholine unit (PMEO2B) having a diethylene
      oxide chain between the phosphorylcholine group and the backbone. The surface
      density of the phosphorylcholine groups and their orientation under aqueous
      conditions were analyzed with an X-ray photoelectron spectroscope. On the PMEO2B
      surface, the surface density of phosphorylcholine groups was much higher than
      that of the theoretical value even when the surface was in air atmosphere. The
      period for equilibrating the surface of PMEO2B by hydration was shorter than that
      of the 2-methacryloyloxyethyl phosphorylcholine polymer (PMB). The mobility of
      the polymer chain with hydration was remarkably improved with the addition of a
      diethylene oxide chain as a bridging unit. The platelet activation and adhesion
      were evaluated using a non-woven fabric made from poly(ethylene terephthalate)
      fibers and that coated with these phosphorylcholine polymers. Even when the
      platelets were passed through the PMEO2B-coated fabric without prehydration, the
      activity of the platelets eluted was similar to that of native platelets.
      Moreover, adherent cells were not observed on the fabric. On the other hand, the
      platelets adhered to the PET fabric and to that coated with PMB. Based on these
      results, we concluded that the higher mobility of the polymer chain is very
      important to reduce interactions with platelets.

PMID- 12809790
TI  - Antibacterial activity of bactericide-immobilized filler for resin-based
      restoratives.
AB  - This study examined the antibacterial activity of prepolymerized resin filler, in
      which the bactericide quaternary ammonium was immobilized. The experimental
      filler was prepared by grinding prepolymerized resin blocks of methacrylate
      monomers, silica particles, and the antibacterial monomer
      methacryloyloxydodecylpyridinium bromide (MDPB). The number of Streptococcus
      mutans after incubation for 18h in contact with the experimental filler with or
      without protein adsorption by saliva treatment was determined, and adherence of
      bacteria to the filler surface was evaluated by scanning electron microscopy.
      Elution of unpolymerized MDPB from the filler and its influence on bacterial
      growth were also investigated. The growth of S. mutans was completely inhibited
      by contact with the experimental filler without saliva treatment. Although the
      effects were attenuated, the saliva-treated filler still exhibited growth
      inhibition at >99.9%. Less bacteria attached to the experimental filler than the
      control filler without MDPB, indicating that the reduction in bacterial number
      after contact with the experimental filler was not due to bacterial adherence to
      the particles. Unpolymerized MDPB at 1 microg/ml was eluted from the filler
      particles but was confirmed to have little effect on bacterial growth. The
      results indicate that the bactericide-immobilized filler containing MDPB shows
      significant bacteriostatic effects without releasing antibacterial components,
      and is useful for incorporation into various resin-based restoratives.

PMID- 12809791
TI  - The removal torque of titanium screw inserted in rabbit tibia treated by dual
      acid etching.
AB  - Chemical acid etching alone of the titanium implant surface have the potential to
      greatly enhance osseointegration without adding particulate matter (e.g. TPS or
      hydroxyapatite) or embedding surface contaminants (e.g. grit particles). The aims
      of the present study were to evaluate any differences between the machined and
      dual acid etching implants with the removal torque as well as topographic
      analysis. A total of 40 custom-made, screw-shaped, commercially pure titanium
      implants with length of 5 mm and an outer diameter of 3.75 mm were divided into 4
      groups, 10 screws in each, and chemical modification of the titanium implant
      surfaces were achieved using HF and HCl/H(2)SO(4) dual acid etching. The first
      exposure was to hydrofluoric acid and the second was to a combination of
      hydrochloric acid and sulfuric acid. The tibia metaphysics was exposed by
      incisions through the skin, fascia, and periosteum. One implant of each group was
      inserted in every rabbit, 2 in each proximal tibia metaphysics. Every rabbit
      received 3 implants with acid etched surfaces and 1 implant with a machined
      surface. Twelve weeks post-surgically, 7 rabbits were sacrificed, Subsequently,
      the leg was stabilized and the implant was removed under reverse torque rotation
      with a digital torque gauge (Mark-10 Corporation, USA) (Fig. 1). Twelve weeks
      after implant placement, the removal torque mean values were the dual acid etched
      implants (24%HF+HCl/H(2)SO(4), group C) required a higher average force (34.7
      Ncm), than the machined surface implants (group A) (p=0.045) (Mann-Whiteney
      test). Scanning electron micrographs of acid etching of the titanium surface
      created an even distribution of very small (1-2 microm) peaks and valleys, while
      machining of the titanium surface created typical microscopically grooved surface
      characteristics. Nonetheless, there was no difference in surface topography
      between each acid etched implant groups. Therefore, chemically acid etching
      implant surfaces have higher strengths of osseointegration than machined implant
      surfaces. There is less correlation between removal torque and the difference in
      HF volume%.

PMID- 12809792
TI  - Evaluation of the silver iontophoretic catheter in an animal model.
AB  - Silver iontophoretic catheters (SIC) were shown to be highly efficacious in
      preventing catheter infections in vitro and in a rabbit model (J. Infect. Dis.
      173 (1996) 495). Furthermore, we sought to determine the safety and durability of
      SIC prior to use in humans. A total of 30 New Zealand white rabbits (3-4 kg) were
      randomly assigned to one of three groups whereby SIC or Arrow Guard (AG)
      catheters were tunneled and inserted in the jugular vein. All animals were
      followed for 2-12 weeks after catheter implantation. Blood was collected from
      each rabbit for assessment of toxicity and determination of silver levels. The
      electrical current generated by each SIC was measured once daily. At the end of
      the follow-up period, tissue samples were collected from the skin surrounding the
      catheter, the lungs, spleen, and liver. Microscopically, none of the tissues
      examined from any of the animals showed evidence of silver deposits, silver
      toxicity, thermal or electrical injury. The silver levels in the animals that
      received the SIC ranged from 0.1 to 2.23 microg/l with a mean of 0.62 (+/-0.44
      SD). In conclusion SIC were safe with normal serum silver levels and were not
      associated with any local or systemic toxicity.

PMID- 12809793
TI  - Structural and mechanical properties of the organic matrix layers of nacre.
AB  - The type of nanostructure referred to in biomineralization as a mineral bridge
      has been directly observed and measured in the organic matrix layers of nacre by
      transmission electron microscopy and scanning electron microscopy. Statistical
      analysis provides the geometric characteristics and a distribution law of the
      mineral bridges in the organic matrix layers. Experiments reveal that the
      nanostructures significantly influences the mechanical properties of the organic
      matrix layers. In addition, the mechanical analysis illustrates the effects of
      the nanostructures on the behaviors of the organic matrix layers, and the
      analytical results explain the corresponding experimental phenomena fairly well.
      The present study shows that the mineral bridges play a key role in the
      mechanical performances of the organic matrix layers of nacre. The results
      obtained provide a guide to the interfacial design of synthetic materials.

PMID- 12809794
TI  - Dopaminergic excitation of the goat carotid body is mediated by the serotonin
      type 3 receptor subtype.
AB  - The purpose of the present study was to use chemoafferent recordings from the
      goat carotid body (CB) to pharmacologically identify the putative low affinity
      excitatory receptor for dopamine (DA). Close arterial injections of DA (1-50
      microg kg(-1)) induced a dose-dependent excitatory burst followed by inhibition
      of the CB chemoafferent activity. The inhibition is likely DA D(2) receptor
      mediated as it was blocked by domperidone (0.5-1.0 mg kg(-1) iv). The initial
      high frequency burst of CB chemoafferent activity could not be attenuated by
      selective antagonists for the DA D(1-4) receptors but could be blocked by D
      tubocurarine or the selective serotonin(3) (5-HT(3)) receptor antagonists,
      tropisetron and MDL72222. The selective nicotinic antagonists, hexamethonium and
      vecuronium, were without effect. Selective blockade of the 5-HT(3)-receptor
      subtype using tropisetron significantly reduced both normoxic and hypoxic unitary
      CB discharge. These results suggest that DA-mediated excitation of the goat CB
      chemosensitive afferents occurs via the 5-HT(3)-receptor subtype and that the 5
      HT(3)-receptor may exert an excitatory modulation of CB output during normal
      physiological responses in the goat.

PMID- 12809795
TI  - Effects of C fiber blockade on cardiorespiratory responses to laryngeal
      stimulation in concious lambs.
AB  - The primary aim of the study was to explore cardiorespiratory reflexes
      originating from laryngeal C fiber endings in the neonatal period. Seventeen
      lambs were instrumented for recording glottal adductor and diaphragm EMG, heart
      rate, systemic arterial pressure and respiratory movements. C fiber blockade was
      induced in eight lambs by 30 mg/kg capsaicin, the remaining nine lambs serving as
      controls. Cardiorespiratory reflexes were induced in non-sedated lambs by flowing
      air, menthol or 13% CO2, or by injecting water or 50 microg capsaicin in the
      laryngeal inlet through an endoscope. Responses to all stimuli but capsaicin were
      similar between the two groups. While cardiorespiratory responses were induced by
      capsaicin in control lambs, the responses were significantly inhibited in lambs
      with C fiber blockade. We conclude that laryngeal C fiber endings are functional
      and responsible for laryngeal chemoreflexes in newborn lambs.

PMID- 12809796
TI  - Hypercapnia-induced activation of brainstem GABAergic neurons during early
      development.
AB  - During early development, GABAergic mechanisms contribute to the regulation of
      respiratory timing in response to CO2. In 5-7 day old piglets, a double labeling
      technique was used to determine whether GABA-containing neurons are activated by
      normoxic hypercapnia (10% CO2, 21% O2, and 69% N2). The c-Fos gene encoded
      protein (c-Fos) was employed to localize CO2 activated cells within the piglet
      medulla oblongata. Parvalbumin was used as a marker for GABAergic neurons. In
      animals breathing room air, only scant c-Fos-like immunoreactive neurons were
      observed. A marked increase in c-Fos positive cells was induced after a 60 min
      exposure to hypercapnia. Colocalization studies revealed that hypercapnia
      significantly increased c-Fos expression in GABA-containing neurons in the
      medulla oblongata, especially in the ventral aspect of the medulla, within the
      Botzinger region, the gigantocellular reticular nucleus, and the caudal raphe
      nuclei. Only a few double-labeled cells were observed within the nucleus tractus
      solitarius. Therefore, brainstem GABAergic neurons are part of the neural
      networks that respond to CO2 and may contribute to respiratory frequency
      responses to hypercapnia during early development.

PMID- 12809797
TI  - Effects of afferent input on the breathing pattern continuum in the tambaqui
      (Colossoma macropomum).
AB  - This study used a decerebrate and artificially-ventilated preparation to examine
      the roles of various afferent inputs in breathing pattern formation in the
      tambaqui (Colossoma macropomum). Three general breathing patterns were observed:
      (1) regular breathing; (2) frequency cycling and (3) episodic breathing. Under
      normoxic, normocapnic conditions, 50% of control fish exhibited regular
      continuous breathing and 50% exhibited frequency cycling. Denervation of the
      gills and oro-branchial cavity promoted frequency cycling. Central denervation of
      the glossopharyngeal and vagus nerves produced episodic breathing. Regardless of
      the denervation state, hyperoxia produced either frequency cycling or episodic
      breathing while hypoxia and hypercarbia shifted the pattern to frequency cycling
      and continuous breathing. We suggest that these breathing patterns represent a
      continuum from continuous to episodic breathing with waxing and waning occupying
      an intermediate stage. The data further suggest that breathing pattern is
      influenced by both specific afferent input from chemoreceptors and generalised
      afferent input while chemoreceptors specific for producing changes in breathing
      pattern may exist in fish.

PMID- 12809798
TI  - Ventilatory load compensation response to long-term chest compression in rat
      model.
AB  - Short-term chest compression has been shown to decrease tidal volume and increase
      respiratory frequency. The present study was designed to assess and characterize
      the effect of long-term chest compression on breathing pattern and blood gases in
      awake rats. Chest compression was carried out by inflating a pneumatic cuff
      placed around the chest to a pressure of 25 mmHg and the pressure was maintained
      for 28 days. Respiratory frequency increased progressively until 14 days after
      chest compression whereas a decrease in tidal volume was stabilized within 3 days
      after chest compression. Although the changes in minute ventilation were small
      and no substantial change in Pa(CO2) was observed, an impairment of weight gain
      and a decrease in body temperature with a concomitant hypoxemia were evident
      during sustained chest compression. These observations suggest that the
      ventilatory response to chest compression may involve not only neural reflex
      mechanisms but also other non-reflex mechanisms. Sustained chest compression
      possibly impairs growth and metabolism.

PMID- 12809799
TI  - Accounting for flow dependence of respiratory resistance during exercise.
AB  - Studies of airway function during exercise have produced conflicting results both
      in healthy and diseased subjects. Respiratory resistance (Rrs) was measured using
      an impulse oscillation technique. A flow/resistance curve was established for
      each of 16 healthy males during voluntary hyperventilation (VHV) at rest. Then,
      Rrs and flow were measured immediately (t(0)) and 90 sec (t(90)) after exercise
      on a cycle ergometer at 60, 70, and 80% of maximal aerobic power. The
      flow/resistance relationship at rest during VHV was used to assess the flow
      dependence of Rrs. Rrs at t(0) was higher than at rest (P <0.01) but lower than
      Rrs obtained at matched flow during VHV (P <0.05). In healthy subjects, the
      linear increase in Rrs with VHV indicates airflow dependency of Rrs following
      Rohrer's equation. The relative decrease in Rrs with exercise suggests
      bronchodilation. The bronchodilating effect disappeared promptly when exercise
      was stopped suggesting that it may have been related to a reflex mechanism.

PMID- 12809800
TI  - A tidal ventilation model for oxygenation in respiratory failure.
AB  - We develop tidal-ventilation pulmonary gas-exchange equations that allow
      pulmonary shunt to have different values during expiration and inspiration, in
      accordance with lung collapse and recruitment during lung dysfunction (Am. J.
      Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against
      published animal data from intravascular oxygen tension and saturation sensors.
      These equations provide one explanation for (i) observed physiological phenomena,
      such as within-breath fluctuations in arterial oxygen saturation and blood-gas
      tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions.
      We suggest that tidal-ventilation models are needed to describe within-breath
      fluctuations in arterial oxygen saturation and blood-gas tension in acute
      respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen
      saturation and tension fluctuations, and the mean oxygen blood-gas values, are
      affected by physiological variables such as inspired oxygen concentration, lung
      volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in
      pulmonary shunt during the respiratory cycle.

PMID- 12809801
TI  - SARS: at least and at last, are we learning from the worst?

PMID- 12809802
TI  - Comparative population dynamics of mosquito-borne flaviviruses.
AB  - Among the members of the genus Flavivirus are several important human pathogens,
      including the dengue (DEN) and Japanese encephalitis (JE) viruses. From the
      analysis of gene sequence data of samples of these virus populations it is
      possible to infer phylogenetic relationships, which in turn can yield important
      epidemiological information, including their demographic history in humans. In
      this study, we use a recently developed method, based on coalescent theory, to
      infer the population dynamics of a variety of mosquito-borne flaviviruses. Our
      study involves the testing of alternative hypotheses, the estimation of
      confidence intervals around demographic model parameter values, and the placing
      of the maximum likelihood (ML) demographic model into a "real time"
      epidemiological history. We reveal that all the Flavivirus populations studied
      are growing at an exponential rate, with the rates of population growth of dengue
      virus serotypes 2 and 3 increasing rapidly in the recent past, and that of
      Japanese encephalitis virus changing from constant population size to exponential
      growth within the last century. We therefore demonstrate that the use of these
      coalescent methods may be extremely valuable in monitoring responses to
      interventions such as vaccination or vector control.

PMID- 12809803
TI  - A fluorescent based PCR assay for the detection and quantitation of Giardia
      duodenalis genotypes in mixed populations.
AB  - A method based on the polymerase chain reaction has been developed for
      differentiating between genotypically and phenotypically distinct strains of
      Giardia duodenalis and quantifying the amount of initial template of the
      different genotypes in mixed populations. The assay relies on a sequence-specific
      probe, labelled with two fluorescent dyes, designed to bind within the small
      subunit ribosomal (SSU) RNA gene. This target region is amplified by primers
      specific for either Group 1 or Group 2-type isolates of G. duodenalis and the
      probe binds within the primer-targeted region. This quantitative method takes
      advantage of the 5' nuclease activity of Taq DNA polymerase, which, on
      encountering a probe bound within the target DNA sequence cleaves it, causing it
      to become dissociated from the template. When the two fluorescent dyes bound to
      the probe are in close proximity (when the probe is intact), the interaction of
      the two dyes prevents the reporter dye from fluorescing. However, during the
      extension phase of amplification, the activity of the DNA polymerase causes the
      dyes to become separated and hence the reporter dye increases its fluorescent
      intensity. This release of fluorescence is directly related to the amplified
      amount of target template. This assay was developed with the aim of providing a
      unique method with which to investigate interactions within mixed populations of
      genetically distinct strains of G. duodenalis.

PMID- 12809804
TI  - Transformation of Rhodococcus rhodnii, a symbiont of the Chagas disease vector
      Rhodnius prolixus, with integrative elements of the L1 mycobacteriophage.
AB  - Elimination of vector populations through the use of insecticides is the
      principal means of controlling Chagas disease. Because of the limitations of
      insecticide use, we have been developing a new potential method of control, to be
      used in conjunction with insecticide programs, a method which utilizes
      genetically modified symbiotic bacteria. These transformed bacteria can express
      anti-parasitic agents in the gut of the bug where the trypanosomes also are
      found. Previous studies have shown that it is possible to transform Rhodococcus
      rhodnii with a shuttle plasmid that contains the gene for cecropin A, an insect
      anti-microbial peptide. The bacteria expressed this peptide and reduced or
      eliminated the number of trypanosomes in the bug Rhodnius prolixus [Proc. Natl.
      Acad. Sci. U.S.A. 94 (1997) 3274]. In an effort to improve efficacy and
      transformation stability, we have begun using plasmids that contain integrative
      elements from the L1 mycobacteriophage to insert DNA into the genome of the
      bacterium. The integrative plasmid pBP5 contains the attachment site (attP) and
      integrase gene (int) of the L1 mycobacteriophage, an antibiotic resistance gene
      and the lacZ gene. After transforming R. rhodnii with pBP5, nine positive clones
      were obtained and six different insertions sites were identified. In each clone,
      the integrative plasmid is inserted only once, the lacZ gene is expressed
      intensely and, all clones but one, remained stable for 100 generations of culture
      in the absence of antibiotic selection. In addition, the construct remains stable
      throughout the life cycle of the bug. These data demonstrate that L1
      mycobacteriophage integrative plasmids are significantly more stable than
      episomally located plasmids used in previous studies and will be greatly
      beneficial for use in the transformation of symbiotic bacteria of Chagas disease
      vectors.

PMID- 12809805
TI  - Evidence for the presence of a type III secretion system in diffusely adhering
      Escherichia coli (DAEC).
AB  - Diffusely adhering Escherichia coli (E. coli) strains (DAEC) represent a
      potential cause of diarrhoea in infants, and the detection of type three
      secretion system (TTSS) genes in DAEC would substantiate their pathogenic nature.
      In this work, four isolates of DAEC, recovered from stools of diarrhoeic
      children, were analysed by PCR, in order to detect the presence of TTSS genes.
      Primers targeted to the escC, escJ, escN and escV, some of the most conserved
      TTSS genes in enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and
      EHEC), were used in order to verify the occurrence of homologous genes in our
      DAEC isolates. By this approach, we were able to characterise DNA fragments
      corresponding to putative escJ and escN genes in all DAEC isolates. Furthermore,
      DNA fragments homologous to the escC and escV genes were also amplified from all
      isolates. Besides the similarity found among the DAEC esc homologues with EPEC
      and EHEC esc genes, the nucleotide sequence analysis of the flanking regions of
      the amplified DNA fragments suggests that the putative DAEC esc genes are
      organised in the same manner as observed in EPEC and in EHEC strains. The results
      described here provide strong evidence for the presence of a TTSS in the DAEC
      strains analysed, implicating a pathogenic nature of these isolates.

PMID- 12809806
TI  - Genotypically distinct Leishmania colombiensis isolates from Venezuela cause both
      cutaneous and visceral leishmaniasis in humans.
AB  - Cutaneous leishmaniasis in Venezuela has been associated with different
      Leishmania species and the visceral form is frequently related to L. chagasi.
      However, in this study we have characterized as L. colombiensis by molecular
      techniques some isolates of Leishmania from patients presenting either cutaneous
      or visceral leishmaniasis. Three different molecular markers (two DNA and one
      protein) were used to investigate the diversity among the L. colombiensis
      isolates. The analysis revealed the isolates to be similar although distinct from
      the reference strain of L. colombiensis. Slight variation among the isolates
      could not be correlated with any epidemiological features of the samples however
      the visceral isolates were observed to cluster on a phenetic tree derived from
      one DNA marker. The results confirm previous findings that L. colombiensis can
      cause both the cutaneous and visceral forms of the disease and that there exists
      at least two distinct etiological agents of American visceral leishmaniasis
      (AVL). The report also shows the necessity of careful differentiation of
      leishmanial isolates in any clinical or epidemiological study of human
      leishmaniasis.

PMID- 12809807
TI  - Genotyping of the Mycobacterium tuberculosis complex using MIRUs: association
      with VNTR and spoligotyping for molecular epidemiology and evolutionary genetics.
AB  - The recent introduction of molecular methods has gained increased acceptance as a
      powerful tool for epidemiology and phylogeny of tuberculosis (TB). In this
      investigation, the efficiency of molecular typing using mycobacterial
      interspersed repetitive units (MIRUs) was assessed on a set of 116 Mycobacterium
      tuberculosis complex clinical isolates from 11 different geographic origins. The
      results obtained were compared with spoligotyping and variable number of tandem
      DNA repeats (VNTRs) typing data. Eighty-nine different MIRU profiles were
      obtained on the sample studied. Spoligotyping- or VNTR-defined clusters were
      split into subclusters by MIRU typing. Conversely, almost all of the clinical
      isolates clustered by MIRUs were shown to belong to spoligotyping-based defined
      clusters. The calculation of the discriminative power by the Hunter-Gaston index
      (HGI) for VNTR, spoligotyping and MIRU typing gave the values of, respectively,
      0.959, 0.965 and 0.988, showing the high discriminative power of the MIRUs. The
      allelic diversity of the sample was calculated for each of the MIRU-VNTR loci;
      five MIRU loci (MIRU nos. 10, 23, 26, 31 and 40) were "highly discriminant", four
      (MIRU nos. 4, 16, 24 and 39) were "moderately discriminant", and three (MIRU nos.
      2, 20 and 27) were "poorly discriminant". Among the three complementary VNTRs
      (exact tandem repeats ETR-A, ETR-B and ETR-C), ETR-A was the most discriminant
      locus. A combined numerical analysis of spoligotyping, VNTR and MIRU typing
      results partly corroborated a recently hypothesized evolutionary scenario for the
      M. tuberculosis complex. M. canettii would be the first branch to have diverged
      from a common M. tuberculosis complex ancestor. The East-African Indian (EAI)
      clade could be the first family to have diverged thereafter. A third branching
      separated a M. africanum-M. bovis clade, followed by a node separating Beijing
      versus non-Beijing M. tuberculosis. The Beijing clade was distinct from the
      Central Asian 1 (CAS1) family. Among non-Beijing strains, branches such as the
      Latin-American and Mediterranean (LAM), X and Haarlem clades diverged later. In
      conclusion, the results obtained show the congruence between clades defined by
      spoligotyping, and MIRU-VNTR, and underline the potential of these methods for M.
      tuberculosis phylogeny reconstruction. We also conclude that MIRU typing is a
      very promising method that may be used in a "two PCR-based" genotyping strategy,
      in conjunction to conventional epidemiological investigations.

PMID- 12809808
TI  - Transmission dynamics of Toxoplasma gondii on a pig farm.
AB  - Transmission of Toxoplasma gondii infection on a pig farm in New England was
      investigated using genetic and ecological methods to (i) determine if infection
      of pigs was a result of a single source, such as in an epizootic situation (e.g.
      outbreak) or of multiple sources, such as in an enzootic situation, (ii) identify
      the main source species of infection to pigs and (iii) evaluate the role of the
      environment surrounding the farm as the source of infection on the farm. Genetic
      characterization of 25 T. gondii isolates from market pigs revealed three
      distinct genotypes with no evidence of recombinants. These data imply that at
      least three distinct exposure events occurred during the 7-month lifespan of
      these pigs. This genotype diversity is consistent with enzootic transmission of
      T. gondii on the farm. Cats were suspected as the main source of pig infection
      based on the high seroprevalence (>95%) in pigs. The presence of the two most
      common T. gondii genotypes in eight isolates from free ranging chickens on this
      farm corroborated the role of cats because chickens were probably infected
      through ingestion of oocysts in the soil. The seroprevalence of toxoplasmosis in
      163 wild mammals and birds captured around the pig sties (overall 13.1%)
      increased with proximity to the pig sties. Thus, transmission of T. gondii was
      higher near the pig sties than in the surrounding environment probably because of
      increased density of oocysts there. We propose that the farm does not simply
      reflect its surroundings in terms of strain composition and risk of infection,
      but that it acts as a reservoir of strains from which the outflow of new
      infections into its surrounding environment is higher than the inflow.

PMID- 12809809
TI  - Identification of Trypanosoma brucei circulating in a sleeping sickness focus in
      Cote d'Ivoire: assessment of genotype selection by the isolation method.
AB  - Genetic studies of Trypanosoma brucei have been mainly based on rodent
      inoculation (RI) for isolation of trypanosome strains. However, Trypanosoma
      brucei gambiense is difficult to grow in rodents. The development and use of the
      Kit for In Vitro Isolation (KIVI) of trypanosomes has led to a better isolation
      success. However, some authors report a genetic monomorphism in T. b. gambiense,
      and the extensive use of the KIVI was suspected as being responsible for this low
      genetic diversity. In the present work, trypanosome stocks were isolated from
      both humans and pigs in an active sleeping sickness focus in Cote d'Ivoire. Two
      methods were simultaneously used for this purpose: KIVI and rodent inoculation.
      None of the human stocks grew in rodents. Some of the stocks originating from
      pigs could be isolated with both methods. Each of these stocks (from the same
      pig) showed a different isoenzymatic pattern according to the isolation method
      used. All the human stocks identified belonged to the major zymodeme 3 of T. b.
      gambiense group 1, whereas the stocks isolated from pigs belonged to a new group
      of zymodemes even if they were genetically closely related. These observations
      may have significant implications when analysing the population structure of T.
      brucei, and also raise again the question of the importance of the animal
      reservoir in Human African Trypanosomiasis (HAT).

PMID- 12809811
TI  - Colonic manometry: for children only? A typical case of paradoxical motility.

PMID- 12809812
TI  - 6-TG for IBD. simple, but safe?

PMID- 12809813
TI  - A link between leptin and steatosis in chronic hepatitis C? Time to weigh up the
      fats.

PMID- 12809814
TI  - Elevated AST or ALT to nonalcoholic fatty liver disease: accurate predictor of
      disease prevalence?

PMID- 12809815
TI  - The prevalence and etiology of elevated aminotransferase levels in the United
      States.
AB  - Chronic liver disease is a major cause of morbidity and mortality in the United
      States. Although often used to detect liver disease, the prevalence and etiology
      of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr
      and older (N = 15,676) from the Third National Health and Nutrition Examination
      Survey (1988-1994). Participants were classified as having elevated
      aminotransferase levels if either aspartate aminotransferase or alanine
      aminotransferase was elevated above normal. Aminotransferase elevation was
      classified as "explained" if there was laboratory evidence of hepatitis B or C
      infection, iron overload, or if there was a history of alcohol consumption.
      Analyses were weighted to provide national estimates. The prevalence of
      aminotransferase elevation in the United States was 7.9%. Aminotransferase
      elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in
      Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic
      whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection
      and high transferrin saturation were found in only 31.0% of cases.
      Aminotransferase elevation was unexplained in the majority (69.0%). In both men
      and women, unexplained aminotransferase elevation was significantly associated
      with higher body mass index, waist circumference, triglycerides, fasting insulin,
      and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05).
      Aminotransferase elevation was common in the United States, and the majority
      could not be unexplained by alcohol consumption, viral hepatitis or
      hemochromatosis. Unexplained aminotransferase elevation was strongly associated
      with adiposity and other features of the metabolic syndrome, and thus may
      represent nonalcoholic fatty liver disease.

PMID- 12809816
TI  - Concepts in pathogenesis and treatment of chronic anal fissure--a review of the
      literature.
AB  - OBJECTIVE: Chronic anal fissures are associated with a persistent hypertonia and
      spasm of the internal anal sphincter. Classic treatment is surgical
      sphincterotomy to reduce the anal tone and eliminate sphincteric spasm. However,
      concerns have been raised about the incidence of fecal incontinence after
      surgery. Therefore, pharmacological means to treat chronic anal fissures have
      been explored. METHODS: We conducted a literature review on MEDLINE database.
      RESULTS: All treatments address the anomaly of a high anal pressure. Several
      studies have investigated the effect of topical glyceryl trinitrate ointment.
      Healing rates range from 30% to 86%. Therapy is limited because of a high
      incidence of moderate to severe headaches in up to 84% of patients. Comparable
      results are observed after injection of botulinum toxin into the anal sphincter
      (43-96%). Minor incontinence for flatus and soiling has been reported in up to
      12% of patients. Further pharmacological approaches including treatment via
      calcium channel blockade and treatment with alpha-adrenoceptor antagonists are
      still at a developmental stage. CONCLUSIONS: Topical glyceryl trinitrate ointment
      and injection of botulinum toxin into the anal sphincter are advocated as the
      first-line treatment for chronic anal fissure. Lateral sphincterotomy should be
      offered to patients with relapse and therapeutic failure of prior pharmacological
      treatment.

PMID- 12809817
TI  - Gastric mucosa-associated lymphoid tissue lymphoma.
AB  - The connection between Helicobacter pylori and gastric mucosa-associated lymphoid
      tissue (MALT) lymphoma is well established. H. pylori infection causes an
      immunological response, leading to chronic gastritis with formation of lymphoid
      follicles within the stomach. These lymphoid follicles resemble nodal tissues
      found throughout the body and are composed of reactive T cells and activated
      plasmal cells and B cells. The B cells are responsible for initiating a clonal
      expansion of centrocyte-like cells that form the basic histology of MALT
      lymphoma. Early diagnosis of MALT lymphoma is difficult but essential for
      adequate treatment. Clinical symptoms are vague and varied, with abdominal pain
      being a common presenting complaint. The endoscopic appearance of this tumor is
      varied and can be infiltrative, exophytic, or ulcerative. In addition, the tumor
      can have a multifocal distribution, and therefore aggressive tissue sampling is
      crucial for diagnosis. Endoscopic ultrasound is essential to document the extent
      of disease and is more accurate than CT scan in detection of spread to
      perigastric lymph nodes. Lesions that are confined to the mucosa or submucosa of
      the gastric wall are believed to be dependent on H. pylori stimulation and
      therefore can be successfully treated with H. pylori eradication. Those MALT
      lymphomas that present at more advanced stages require more aggressive management
      and can be treated with surgical resection, radiation, or chemotherapy. Follow-up
      is critical in all patients who have been treated with H. pylori eradication and
      consists of multiple endoscopic biopsies for histological and molecular studies
      as well as endoscopic ultrasound at 3, 6, and 12 months after treatment. The
      reappearance of MALT lymphomas has been seen years after treatment, and therefore
      follow-up of these patients should be indefinite.

PMID- 12809818
TI  - Asthmatics with gastroesophageal reflux: long term results of a randomized trial
      of medical and surgical antireflux therapies.
AB  - OBJECTIVE: In short term studies, asthma symptoms and pulmonary function have
      been reported to improve during and after medical treatment or surgical
      correction of gastroesophageal reflux (GER). In this study, we aimed to determine
      whether prolonged treatment of GER altered the long term natural history of
      asthma in asthmatics with GER. METHODS: A total of 62 patients with both GER and
      asthma entered a randomized study of antireflux treatments for at least 2 yr: 24
      controls (antacids as needed); 22 medical (ranitidine 150 mg t.i.d.); and 16
      surgical (Nissen fundoplication). Asthma was defined as a previous diagnosis of
      asthma with discrete attacks of wheezing and 20% reversibility in airway disease.
      GER was defined as an abnormal ambulatory 24-h esophageal pH test and macroscopic
      or microscopic evidence of GER disease. Overall clinical status, asthma symptom
      scores, and pulmonary medication requirements were recorded monthly. Peak
      expiratory flow rates were recorded up to seven times per day for 1 wk of each
      month throughout the years. Pulmonary function, esophageal manometry, and
      endoscopy with biopsy were repeated yearly. RESULTS: The 62 patients were
      followed for up to 19.1 yr. In the surgical group, but not in the medical or
      control groups, there was an immediate and sustained reduction in acute nocturnal
      exacerbations of wheezing, coughing, and dyspnea. By the end of 2 yr,
      improvement, marked improvement, or cure in the overall asthma status occurred in
      74.9% of the surgical group, 9.1% of the medical group and 4.2% of the control
      group, whereas the overall status worsened in 47.8% of the control group, 36.4%
      of the medical group, and 12.5% of the surgical group (p < 0.001, surgical vs
      medical and control). The mean asthma symptom score of the surgical group
      improved 43%, compared with less than 10% in the medical and control groups (p =
      0.0009). As determined by changes in peak expiratory flow rates, there was no
      statistically significant difference in pulmonary function during the 2-yr period
      or during regularly scheduled follow-up. There was no difference in medication
      requirements among the groups. There was no difference between the groups in
      overall survival. CONCLUSION: In patients with both GER and asthma, antireflux
      surgery (but not medical therapy with ranitidine 150 mg t.i.d.) has minimal
      effect on pulmonary function, pulmonary medication requirements, or survival, but
      significantly improves asthma symptoms and overall clinical status.

PMID- 12809819
TI  - Esophageal contractions and oropharyngeal and esophageal transits in patients
      with iron deficiency anemia.
AB  - OBJECTIVE: Patients with iron deficiency may have reduced power of the pharyngeal
      muscle for bolus propulsion into the esophagus. We hypothesized that esophageal
      muscle is similarly impaired. METHODS: We studied the oropharyngeal and
      esophageal transits and esophageal motility of 12 patients (11 women) aged 31-50
      yr (median 36 yr) with iron deficiency anemia (serum iron less than 40 microg/dl)
      and 17 normal volunteers (16 women) aged 26-52 yr (median 37 yr) with serum iron
      greater than 60 microg/dl. The esophageal motility was studied by the manometric
      method, with continuous perfusion and 10 swallows of a 2-ml bolus of water
      alternated with 10 swallows of a 7-ml bolus; and the oropharyngeal and esophageal
      transits were studied by scintigraphy, with swallows of a 10-ml bolus for the
      study of oropharyngeal transit and of a 10-ml bolus for the study of esophageal
      transit. Motility and transit were studied in the supine position. RESULTS: The
      amplitude, duration and area under the curve of contractions were lower in
      patients than in volunteers. There were no differences in peristaltic contraction
      velocity, lower esophageal sphincter pressure, and lower esophageal sphincter
      relaxation duration. There was no difference in oropharyngeal transit. In the
      esophagus the transit was slower in patients than in volunteers. The time needed
      by the scintigraphic activity to reach a peak in the proximal esophagus was
      longer in patients than in volunteers. CONCLUSIONS: Iron deficiency may decrease
      esophageal contractions and impair esophageal transit.

PMID- 12809820
TI  - Studies regarding the mechanism of false negative urea breath tests with proton
      pump inhibitors.
AB  - OBJECTIVE: The mechanism of false negative urea breath tests (UBTs) results among
      proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI
      associated negative UBT, the relation to Helicobacter pylori density, and whether
      gastric acidification would prevent false negative UBT results. METHOD: In the
      UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d.
      for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and
      1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment,
      after a wash-out of >5 months, nine of the original subjects were rechallenged
      with omeprazole for 6.5 days. Antral and corpus biopsies for histology and
      culture were done before and 1 day after PPI administration. RESULTS: Thirty
      subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day
      6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT
      recovered in all but one subject by the fourth day post-PPI and in all subjects
      by day 14. In the culture and histology experiment, upon PPI rechallenge, three
      of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by
      culture or histology, decreased with PPI therapy; antral biopsies became
      histologically negative in five subjects and corpus biopsies in three subjects.
      CONCLUSION: PPI-induced negative UBT results were related to the anti-H. pylori
      effect of the PPI. Acidification of the stomach did not prevent false negative
      UBT results. Three days is likely the minimum delay from stopping PPI until one
      should perform a test for active infection. A delay of 14 days is preferred.

PMID- 12809821
TI  - The clinical role of cytochrome p450 genotypes in Helicobacter pylori management.
AB  - OBJECTIVE: The aim of this pharmacogenomics study was to investigate the
      influence of different cytochrome P450 (CYP) genotypes in Helicobacter pylori
      eradication therapy. METHOD: The study involved 143 consecutive Italian Caucasian
      patients with H. pylori infection diagnosed and treated with 1-wk triple therapy
      according to European Helicobacter Pylori Study Group guidelines. Using human
      genomic DNA, CYP2C19 (*2 and *3) and CYP3A4 alleles (*1B, *2, and *3) were
      evaluated by polymerase chain reaction-restriction fragment length polymorphism
      assays and confirmed by sequencing the amplicons. RESULT: According to the
      endoscopy-based gold standard, 93 patients achieved H. pylori eradication.
      Regarding CYP2C19 genotype, the 50 patients who remained infected were all
      homozygous or heterozygous extensive metabolizers (homEM or hetEM). Carriers of
      homEM fared significantly less well than those of hetEM; homEM genotype was also
      predictive of failure at univariate/multivariate analysis. Carriers of CYP3A4
      polymorphisms achieved favorable eradication rates similar to patients bearing
      CYP2C19. All four patients with single CYP3A4*2 polymorphism achieved
      eradication, and only 29% (5/17) of all CYP3A4*1B carriers did not achieve
      eradication. All nine patients carrying CYP3A4 polymorphisms in the CYP2C19 hetEM
      subgroup were cured, suggesting the possibility of a positive synergism between
      CYP3A4 and CYP2C19. CONCLUSIONS: This first pharmacogenomics study on the
      influence of different CYP genotypes on H. pylori therapy suggests that, as in
      Asian populations, CYP2C19 genotype patterns are probably also relevant in
      Caucasians receiving H. pylori eradication regimens that include omeprazole. The
      possibility of a favorable drug interaction mediated by CYP2C19 and CYP3A4
      requires investigation.

PMID- 12809822
TI  - Utility of Web-based assessment of patient satisfaction with endoscopy.
AB  - OBJECTIVES: The dramatic growth of the World Wide Web (Web) holds potential for
      use in survey distribution and submission. Its use has not previously been
      studied in the context of patient satisfaction with endoscopy procedures. In this
      study we compared standard mail, telephone, and Web-based modes of endoscopy
      satisfaction survey administration with respect to response rate and response
      content. METHODS: An endoscopy satisfaction questionnaire consisting of seven
      core items from the modified Group Health Association of America (GHAA-9) was
      distributed to patients after routine outpatient endoscopy. Patients were
      randomized to receive the questionnaire by standard mail, telephone, or Web (if
      applicable). Response rates and satisfaction scores in the groups were compared.
      The nonresponders to the standard mail and Web surveys were subsequently
      contacted by telephone to determine their level of satisfaction. RESULTS:
      Response rates to the telephone survey (81% among those designated as non-Web
      users and 78% among Web users) and standard mail (75% non-Web users, 67% Web
      users) were higher than response rate to the Web-based survey (34%) (p < or =
      0.0005). There was no significant difference in satisfaction scores among the
      groups or between satisfaction of nonresponders and responders. CONCLUSIONS: The
      potential of our Web-based survey was limited by poor response rates. This arose
      from privacy protection precautions that complicated access to the Web site.
      Future Web-based strategies for surveying patients will need to be more user
      friendly while maintaining the intent of the recent Health Insurance Portability
      and Accountability Act regulations.

PMID- 12809823
TI  - Endoscopic ultrasound-guided biopsy for the diagnosis of focal lesions of the
      spleen.
AB  - OBJECTIVES: Needle biopsy of splenic lesions using computed tomography (CT) or
      ultrasound (US) is difficult if the size of the lesion is small. It may be
      dangerous if the lesion is adjacent to the splenic hilum or located peripherally.
      We used endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to
      elucidate the tissue diagnosis of splenic abnormalities. METHODS: EUS-FNA was
      performed in 12 patients when US- or CT-guided biopsy was inconclusive (n = 5),
      was not attempted because of small tumor size (0.9-1.4 cm; N = 4), or was
      considered dangerous (n = 3). A linear echo-endoscope and 22-gauge needles were
      used for cytology and bacteriology. RESULTS: The age of the patients was 19-68 yr
      (median 32 yr). Seven patients were male and five female. The size of the lesions
      was 0.8-4.2 cm (median 1.4 cm). Cytology was inadequate in one patient.
      Bacteriology was positive for Staphylococcus aureus and Serratia in one patient
      each, and cultures were positive for Mycobacterium tuberculosis in two patients.
      A positive diagnosis was made in 10 of 12 patients (83%). Final diagnoses were
      tuberculosis in two patients, Hodgkin's disease in two, sarcoidosis in two,
      abscesses in two, metastatic colon cancer in one, and infarction in one.
      Suspected recurrence of non-Hodgkin's lymphoma was not confirmed in one case. One
      patient experienced pain after puncture, but no hematoma was demonstrated on
      subsequent US examination. CONCLUSIONS: EUS-FNA cytodiagnosis in patients with
      unknown splenic lesions seems feasible, even in very small foci, when CT- or US
      guided biopsy fails. Additional material for bacteriology may show benign
      treatable diseases such as abscesses or tuberculosis.

PMID- 12809824
TI  - Clinical utility of stent cytology for the diagnosis of pancreaticobiliary
      neoplasms.
AB  - OBJECTIVE: ERCP is frequently the technique of choice for the diagnosis and
      palliative treatment of pancreaticobiliary neoplasms. The sensitivity of tissue
      sampling techniques has been disappointing. Two small series have reported a high
      diagnostic yield from cytological examination of cellular debris from removed
      biliary stents. The aim of this study was to determine the clinical utility of
      stent cytology for the diagnosis of biliary and pancreatic neoplasia. METHODS:
      Patients who had biliary or pancreatic stents removed at ERCP and evaluated
      cytologically were the subjects of this study. Stents were scraped and washed,
      and the cellular debris was examined cytologically and recorded as positive,
      atypical, or negative. Patient demographics, ductal stricture, and stent
      characteristics were recorded. RESULTS: Between January, 1994 and January, 2001 a
      total of 126 biliary stents from 101 patients (61 male, 40 female, mean age 62
      yr) and 29 pancreatic stents from 19 patients (seven male, 12 female, mean age 58
      yr) were examined. The sensitivity, specificity, positive predictive value, and
      negative predictive value of biliary and pancreatic stents for the diagnosis of
      neoplasia were: 11%, 100%, 100%, 53%, and 25%, 100%, 100%, 77.8%, respectively.
      The sensitivity improved slightly if all degrees of atypia were considered
      positive for neoplasia. The mean duration of stent placement was 93.6 days for
      biliary stents and 43.5 days for pancreatic stents. CONCLUSIONS: Biliary and
      pancreatic stent cytology has limited clinical utility in the diagnosis of
      pancreaticobiliary neoplasia, owing to poor sensitivity. In addition, the time
      lag between stent placement and removal for cytologic examination further limits
      its contribution to patient management.

PMID- 12809825
TI  - Gallstones, gallbladder disease, and pancreatitis: cross-sectional and 2-year
      data from the Swedish Obese Subjects (SOS) and SOS reference studies.
AB  - OBJECTIVES: Obesity and weight loss have been associated with gallstone disease.
      There is also an association between gallstones and pancreatitis. We investigated
      cross-sectional relationships between body mass index (BMI), body fat
      distribution, and prevalence of gallstones, gallbladder disease, and pancreatitis
      in men and women. Furthermore, 2-yr incidences of these disorders were examined
      in relation to changes in weight and body fat distribution after surgical and
      conventional obesity treatment. METHODS: Self-administered questionnaires were
      used to assess biliary and pancreatic disease. In the cross-sectional
      investigation, 6328 obese patients and 1135 randomly selected reference
      individuals were used. Longitudinally, 1422 operated and 1260 conventionally
      treated patients were examined. RESULTS: Obese subjects had significantly higher
      prevalence of cholelithiasis, cholecystitis, cholecystectomies, and pancreatitis
      as compared with the reference population. In women, BMI and waist-hip ratio
      (WHR) were independently related to an increased biliary disease prevalence. In
      men, only BMI was independently associated with biliary disease. Compared with
      conventional treatment, obesity surgery significantly increased the incidence of
      cholelithiasis, cholecystitis, and cholecystectomies in men. There was no
      incidence difference among women. In both genders, weight loss, but not change in
      WHR, was related to an increased incidence of biliary disease. CONCLUSIONS: This
      study showed an increased prevalence of gallstones, gallbladder disease, and
      pancreatitis in the obese. Biliary disease was related to BMI and WHR in women,
      but only to BMI in men. Weight loss, but not change in WHR, increased the risk of
      biliary disease in both genders.

PMID- 12809826
TI  - A questionnaire for the assessment of biliary symptoms.
AB  - OBJECTIVES: Gallstone disease is common and causes high health care costs, but a
      measure of symptomatic biliary disease for outcome studies is lacking. We aimed
      to develop a reproducible, valid, discriminative, disease-specific measure of
      biliary symptoms. METHODS: We created the self-report Biliary Symptoms
      Questionnaire (BSQ) by combining possible biliary symptoms with validated items
      for gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and
      other disorders. We developed the final version through an iterative process and
      assessed reproducibility by the test-retest method, concurrent validity by
      comparing BSQ responses with symptoms obtained by structured interview, and
      discriminative validity by comparing BSQ-based diagnoses of biliary symptoms,
      GERD, and IBS with patients' final diagnoses. A shortened version (sBSQ) also
      underwent reproducibility testing. RESULTS: A total of 245 outpatients (mean age,
      55.2 yr; 61% female) participated. Median completion times for the BSQ and sBSQ
      were 36 and 10 min, respectively. For the BSQ, median kappa values were 0.65
      (range -0.03 to 0.95) for reproducibility and 0.61 (range 0.15-0.95) for
      concurrent validity. Using BSQ responses, investigators distinguished IBS and
      GERD 79-90% of the time. For the sBSQ, the median kappa value for reproducibility
      was 0.72 (range 0.32-0.86). CONCLUSIONS: The BSQ is reproducible and has good
      concurrent and discriminative validity for biliary symptoms. The abridged sBSQ
      has good reproducibility. These instruments may be useful in future outcome
      studies.

PMID- 12809827
TI  - Colonic manometry in children with defecatory disorders. role in diagnosis and
      management.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of colonic manometry in
      clarifying pathophysiology of childhood defecatory disorders and to evaluate its
      impact on management. METHODS: We conducted a retrospective review of medical
      records of children referred to undergo colonic manometry to a tertiary care
      Motility Center from 1996 to 2001. Families were followed up a median of 20
      months after evaluation (range 3-60 months). RESULTS: A total of 150 colonic
      manometries were performed in 146 children (74 male, median age 79 months, range
      4-225 months). Colonic manometry had been requested to clarify the
      pathophysiology of lower GI symptoms in 68%; as part of diagnostic workup for
      chronic intestinal pseudo-obstruction in 11%; to decide about reanastomosis of a
      diverted colon in 7%; and to clarify the pathophysiology of persisting symptoms
      after surgery for Hirschsprung's disease in 14%. Normal motility was found in the
      entire colon in 38% of children. In 17%, there was normal motility in the
      proximal colon with abnormality limited to the dilated distal colon. Abnormal
      motility was found in 45% of children. After colonic manometry, treatment changes
      were recommended in 93% of patients. We were able to follow up 65% of the
      families. When recommendations were followed (96% of the contacted patients), the
      symptoms improved in 78%, were unchanged in 18%, and were worse in 4% of
      patients. Among the parents, 88% believed that the suggestions given after
      colonic manometry had been helpful in improving their children's health.
      CONCLUSIONS: Colonic manometry may provide information useful in guiding therapy
      in a subgroup of patients with defecatory disorders.

PMID- 12809828
TI  - Thioguanine: a potential alternate thiopurine for IBD patients allergic to 6
      mercaptopurine or azathioprine.
AB  - OBJECTIVE: Approximately 10% of inflammatory bowel disease (IBD) patients
      receiving 6-mercaptopurine (6-MP) or azathioprine (AZA) develop drug
      hypersensitivity reactions necessitating early discontinuation of these
      traditional thiopurines. These allergic reactions typically reoccur upon
      rechallenge. Our recently published pilot study suggested that thioguanine (6
      TG), a closely related thiopurine, was efficacious and well tolerated in IBD
      patients resistant to 6-MP/AZA. The aim of this study was to determine if
      hypersensitivity reactions to 6-MP/AZA reoccur with 6-TG therapy. METHODS: IBD
      patients allergic to 6-MP and/or AZA were treated with 6-TG as an alternate
      thiopurine. Hypersensitivity reactions to 6-MP/AZA must have been documented
      within 6 wk of 6-MP/AZA initiation. RESULTS: 6-TG was initiated in 21 IBD
      patients at a median (range) dose of 20 (10-40) mg/day. 6-TG hypersensitivity
      reaction occurred in only four of 21 (19%) patients after a median time interval
      of 9 days. Pancreatitis did not reoccur with 6-TG. Eighty-two percent of 6-TG
      tolerant patients were assessed as improved at last follow-up. CONCLUSIONS: These
      results suggest that 6-TG may be considered as a possible alternate thiopurine in
      patients allergic to traditional 6-MP/AZA. Despite these favorable results,
      candidates for 6-TG should be selected with caution, and its use should be
      reserved for IBD patients well informed about potential toxicities.

PMID- 12809829
TI  - Work losses related to inflammatory bowel disease in the United States: results
      from the National Health Interview Survey.
AB  - BACKGROUND: U.S. studies using varying methodologies have reported different
      estimates for the indirect, or nonmedical cost per person with inflammatory bowel
      disease (IBD). Our analysis contributes to this literature by using the 1999
      sample of the National Health Interview Survey (NHIS) to estimate the work-loss
      effect of IBD on work in the United States and the associated cost to society.
      METHODS: A weighted logistic regression model was used to estimate the OR of
      being out of the labor force as determined by predictive variables, including
      having been diagnosed with IBD, with or without symptoms. Controls included
      health status indicators and demographic variables. For those people in the labor
      force, a second analysis was performed to determine the relative influence of the
      same variables on working less than 12 months versus the entire year. SUDAAN 8.0
      was used to generate population estimates, systematically correcting for survey
      design. RESULTS: Of IBD patients who had experienced symptoms in the past 12
      months, 31.5% reported being out of the labor force (OR = 2.14, relative to the
      non-IBD group). We estimated the excess in the nonparticipation rate attributable
      to IBD with symptoms in the past 12 months in the United States to be 12.3%.
      Based on this, the indirect cost of nonparticipation attributable to IBD in
      1998/1999 was more than $3.6 billion U.S. dollars (USD) or $5228 USD per person
      with IBD and symptoms. According to the second weighted logistic regression, for
      those who are in the labor force, having IBD had no association with the duration
      of work. CONCLUSIONS: By using directly observed data in our analysis, this
      method of estimation can be used to predict the overall paid-employment burden of
      IBD.

PMID- 12809830
TI  - Therapy of travelers' diarrhea with rifaximin on various continents.
AB  - OBJECTIVE: Our aim was to compare the efficacy and safety of rifaximin, a
      virtually nonabsorbed antibiotic, 600 and 1200 mg per day, with placebo in
      patients with travelers' diarrhea. METHODS: This was a multicenter, 1:1:1
      randomized, parallel-group, double-blind study, conducted in Antigua, Guatemala;
      Guadalajara and Morelia, Mexico; and the coast of Kenya north and south of
      Mombasa. Adult patients with acute travelers' diarrhea were recruited; exclusion
      criteria included primarily medication that could influence the outcome. Subjects
      were treated for 3 days, three times daily; follow-up lasted 5 days. For each 24
      h period, the subjects completed a diary card. Pre- and posttreatment stool,
      blood, and urine samples were assessed. RESULTS: Among the 380 volunteers, median
      time to the last unformed stool was 32.5 and 32.9 h in both rifaximin groups,
      compared with 60.0 h with placebo (p = 0.0001). Also, secondary clinical outcome
      measures were favorably influenced by the active agent. No relevant side effects
      were reported. CONCLUSION: Rifaximin is efficacious and safe for treatment of
      travelers' diarrhea at daily doses of 600 mg or higher.

PMID- 12809831
TI  - Reliability of antitransglutaminase antibodies as predictors of gluten-free diet
      compliance in adult celiac disease.
AB  - OBJECTIVE: Strict lifelong compliance to a gluten-free diet (GFD) minimizes the
      long-term risk of mortality, especially from lymphoma, in adult celiac disease
      (CD). Although serum IgA antitransglutaminase (IgA-tTG-ab), like antiendomysium
      (IgA-EMA) antibodies, are sensitive and specific screening tests for untreated
      CD, their reliability as predictors of strict compliance to and dietary
      transgressions from a GFD is not precisely known. We aimed to address this
      question in consecutively treated adult celiacs. METHODS: In a cross-sectional
      study, 95 non-IgA deficient adult (median age: 41 yr) celiacs on a GFD for at
      least 1 yr (median: 6 yr) were subjected to 1) a dietician-administered inquiry
      to pinpoint and quantify the number and levels of transgressions (classified as
      moderate or large, using as a cutoff value the median gluten amount ingested in
      the overall noncompliant patients of the series) over the previous 2 months, 2) a
      search for IgA-tTG-ab and -EMA, and 3) perendoscopic duodenal biopsies. The
      ability of both antibodies to discriminate celiacs with and without detected
      transgressions was described using receiver operating characteristic curves and
      quantified as to sensitivity and specificity, according to the level of
      transgressions. RESULTS: Forty (42%) patients strictly adhered to a GFD, 55 (58%)
      had committed transgressions, classified as moderate (< or = 18 g of gluten/2
      months; median number 6) in 27 and large (>18 g; median number 69) in 28. IgA-tTG
      ab and -EMA specificity (proportion of correct recognition of strictly compliant
      celiacs) was 0.97 and 0.98, respectively, and sensitivity (proportion of correct
      recognition of overall, moderate, and large levels of transgressions) was 0.52,
      0.31, and 0.77, and 0.62, 0.37, and 0.86, respectively. IgA-tTG-ab and -EMA
      titers were correlated (p < 0.001) to transgression levels (r = 0.560 and R =
      0.631, respectively) and one to another (p < 0.001) in the whole patient
      population (r = 0.834, N = 84) as in the noncompliant (r = 0.915, N = 48) group.
      Specificity and sensitivity of IgA-tTG-ab and IgA-EMA for recognition of total
      villous atrophy in patients under a GFD were 0.90 and 0.91, and 0.60 and 0.73,
      respectively. CONCLUSIONS: In adult CD patients on a GFD, IgA-tTG-ab are poor
      predictors of dietary transgressions. Their negativity is a falsely secure marker
      of strict diet compliance.

PMID- 12809832
TI  - High prevalence of fatigue in quiescent inflammatory bowel disease is not related
      to adrenocortical insufficiency.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD) patients, with active as well as
      quiescent disease, frequently complain of fatigue. This often has consequences
      for patients' work and daily lives. The primary aim of this study was to assess
      the prevalence and severity of fatigue in IBD patients in remission. Furthermore,
      we studied the correlation between fatigue and disease activity, quality of life,
      and biochemical and hematological test results, and the role of (secondary)
      hypocortisolism. METHODS: Eighty subjects with proven IBD were included. Disease
      activity was assessed using the Clinical Activity Index for Ulcerative Colitis
      and the Crohn's Disease Activity Index. Quality of life was measured by the
      Inflammatory Bowel Disease Questionnaire, and fatigue was assessed using the
      Multidimensional Fatigue Inventory (MFI). Routine biochemical and hematological
      tests were performed, and basal cortisol was determined. To evaluate
      adrenocortical reserve in subjects with a cortisol level of <0.4 micromol/L, a
      low dose adrenocorticotrophin hormone test was performed. Healthy age- and sex
      matched subjects (n = 67) served as controls. RESULTS: More than 40% of the IBD
      patients in remission suffered from fatigue. Mean MFI scores of the IBD patients
      were comparable to mean MFI scores reported in cancer patients. The Inflammatory
      Bowel Disease Questionnaire showed a negative correlation with the MFI (r = 
      0.735; p < 0.001). No correlation was found between fatigue and basal cortisol
      levels or other laboratory parameters. CONCLUSION: Fatigue is an important
      feature in IBD in remission, adversely affecting the quality of life. It does
      not, however, affect all patients, nor does it seem to be the result of
      hypocortisolism.

PMID- 12809833
TI  - Bone density in a population-based cohort of premenopausal adult women with early
      onset inflammatory bowel disease.
AB  - OBJECTIVE: We aimed to determine the bone mineral density (BMD) using dual energy
      x-ray absorptiometry in a population-based sample of women with inflammatory
      bowel disease who were diagnosed before age 20 yr and who are currently
      premenopausal and less than 45 yr. METHODS: The University of Manitoba
      Inflammatory Bowel Disease Epidemiology Research Registry was accessed to find
      eligible women. Of 171 eligible subjects, 82 agreed to participate, and 70
      appeared for dual energy x-ray absorptiometry. All subjects completed
      demographic, clinical, and lifestyle questionnaires and underwent dual energy x
      ray absorptiometry with analyses for both areal and volumetric BMD. RESULTS: The
      mean areal T scores at the lumbar spine, femoral neck, total hip, and total body
      were -0.14 +/- 1.05, -0.15 +/- 1.04, -0.25 +/- 1.17, and +0.09 +/- 1.04,
      respectively. Forty-five subjects had normal BMD, and 25 had a T score < -1.
      There were no significant differences between these groups for predictive
      variables. Only three (4%) had osteoporosis (T score < -2.5 at any site). There
      were 12 with disease onset before puberty and 58 after puberty. There were no
      differences between these groups for BMD. Volumetric BMD was slightly higher than
      areal BMD at the lumbar spine (p < 0.0002), femoral neck (p < 0.01), and total
      hip (p < 0.001). CONCLUSIONS: In a population-based sample of women diagnosed
      with IBD before 20 yr of age and who are currently premenopausal, their average
      BMD is normal and the prevalence of osteoporosis is very low. Despite the
      potential for children with IBD to develop osteoporosis, their BMD as adults is
      generally normal.

PMID- 12809834
TI  - TNF-alpha -308A promoter polymorphism is associated with enhanced TNF-alpha
      production and inflammatory activity in Crohn's patients with fistulizing
      disease.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the
      inflammatory response and pathogenesis of Crohn's disease (CD). TNF-alpha -308A
      polymorphism within the TNF-alpha gene promoter has been associated with enhanced
      TNF-alpha production in vitro. The aim of this study was to investigate the
      effect of TNF-alpha promoter polymorphism at -308 on the susceptibility and
      phenotypic expression of fistulizing CD. METHODS: The distribution of -308 TNF
      alpha genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy
      matched controls. TNF-alpha, interleukin-1beta, and interleukin-6 serum levels
      were measured by ELISA. Serum amyloid-A, C-reactive protein, alpha1-antitrypsin,
      alpha1-acid glycoprotein, and haptoglobin were measured by nephelometry. RESULTS:
      No significant differences were found in the allele frequencies of the
      polymorphism between patients and controls. However, compared with -308GG
      patients, those carrying -308AG had a significant increase of serum levels of TNF
      alpha (58 +/- 79 vs 8 +/- 19 pg/ml, p < 0.001), interleukin-1beta (36 +/- 45 vs
      16 +/- 20 pg/ml, p = 0.048), and acute phase proteins (APPs). -308A carriers had
      also a higher frequency of arthritis (66% vs 26%, p = 0.039). The logistic
      regression model showed that the patients carrying -308A polymorphism had a
      relative risk for developing arthritis of 5.45 (95% CI = 1.1-25.6). No other
      clinical or analytical findings were predictive for the risk of development of
      arthritis. CONCLUSIONS: TNF-alpha -308A polymorphism is associated with enhanced
      TNF-alpha production, more intense inflammatory activity, and an increased risk
      for arthritis susceptibility in CD patients with fistulizing disease.

PMID- 12809835
TI  - Risk factors for chronic constipation based on a general practice sample.
AB  - OBJECTIVES: Many factors have been associated with the occurrence of
      constipation, particularly poor diet and lack of exercise. However, the
      importance of medications and general medical illnesses in constipation remains
      more uncertain. We aimed to identify risk factors for constipation from among
      patient clinical, therapeutic, and demographic characteristics. METHODS: The
      sample was composed of patients explicitly diagnosed with chronic constipation (n
      = 7251), those diagnosed with constipation of unspecified chronicity (n = 6441),
      and a sample of controls (n = 7103). All were drawn from a general practice
      research database representing more than 10 yr of data collection. RESULTS: A
      large number of clinical and therapeutic factors were independently associated
      with chronic constipation over and above age and gender. Primary neurological
      diseases were strongly associated with constipation but accounted for few cases.
      Opioids (OR = 1.6, population attributable risk [PAR] = 2.6%), diuretics (OR =
      1.7, PAR = 5.6%), antidepressants (OR = 1.9, PAR = 8.2%), antihistamines (OR =
      1.8, PAR = 9.2%), antispasmodics (OR = 3.3, PAR = 11.6%), anticonvulsants (OR =
      2.8, PAR = 2.5%) and aluminum antacids (OR = 1.7, PAR = 3.0%) were associated
      with the highest risk among medications. CONCLUSIONS: Constipation is common in
      primary care, and multiple medications seem to be an important contributing
      factor. Concurrent diseases are also associated but at most are only contributing
      to a minority of cases.

PMID- 12809836
TI  - Treatment of chronic constipation with colchicine: randomized, double-blind,
      placebo-controlled, crossover trial.
AB  - OBJECTIVE: Refractory constipation is a common GI complaint seen by physicians in
      all practice settings. We have previously shown that p.d. colchicine (0.6 mg
      t.i.d.) increases the number of spontaneous bowel movements, hastens GI transit,
      and improves GI symptoms in patients with chronic constipation during an 8-wk,
      open-label therapeutic trial. The aim of this study was to determine if p.d.
      colchicine will increase spontaneous bowel movements and accelerate colonic
      transit in patients with idiopathic chronic constipation in a randomized, placebo
      controlled, crossover trial. METHODS: A total of 16 patients (15 women, one man)
      with a mean age of 47 yr (age range 25-89) with chronic idiopathic constipation
      who were refractory to standard medical therapy participated in the study.
      Patients randomly received either colchicine 0.6 mg p.o. t.i.d. or an identical
      placebo p.o. t.i.d. for a total of 4 wk in a double-blind, crossover fashion.
      Patients recorded their daily number of bowel movements and daily symptoms of
      daily nausea, abdominal pain, and bloating. Mean colonic transit was calculated
      at baseline, weeks 6 and 12. RESULTS: Colchicine increased the number of bowel
      movements and accelerated colonic transit compared with baseline and placebo
      conditions. There were no significant differences between conditions on ratings
      of nausea and bloating. During colchicine administration, mean abdominal pain was
      greater than the baseline or placebo conditions, however, the pain decreased
      significantly by the last week the patient was on colchicine. CONCLUSION:
      Colchicine increases the frequency of bowel movements and hastens colonic transit
      in patients with chronic constipation. Colchicine may be an effective agent
      available to practitioners to treat a subset of patients with chronic
      constipation who are refractory to standard medical therapy.

PMID- 12809837
TI  - Incidence of colonic ischemia, hospitalized complications of constipation, and
      bowel surgery in relation to use of alosetron hydrochloride.
AB  - OBJECTIVE: Alosetron hydrochloride (Lotronex), a potent selective 5
      hydroxytryptamine(3) receptor antagonist, was approved in February, 2000 in the
      United States for the treatment of diarrhea-predominant irritable bowel syndrome
      (IBS) in women. Marketing was suspended in November, 2000, after reports of
      colonic ischemia and serious complications of constipation. We sought to compare
      the incidence of colonic ischemia, hospitalized complications of constipation,
      and bowel surgery among alosetron users and a cohort of patients with IBS who did
      not use alosetron. METHODS: We sought outcomes of colonic ischemia, hospitalized
      complications of constipation, and bowel surgery in 3,631 Lotronex users and
      2,480 comparison IBS subjects using diagnoses, procedures, and drugs recorded in
      the UnitedHealthcare insurance claims database, and validated these by chart
      review. The initial assessment was to last for 3 yr beginning with the start of
      alosetron treatment and was to include 10,000 Lotronex users; however, the
      observation period ended by December 31, 2000, after suspension of marketing.
      RESULTS: There were 3631 alosetron users among members of UnitedHealthcare from
      March through December, 2000, and we identified 2480 comparison IBS-only
      patients; follow-up time averaged about 5 months in both groups. There were no
      instances of colonic ischemia in either cohort. Thirty instances of bowel surgery
      occurred, giving rates of 10.2/1000 person-yr in the alosetron cohort and
      11.8/1000 person-yr in the IBS/no alosetron cohort. There were three cases of
      hospitalized complications of constipation. The incidence rates were essentially
      the same in alosetron users (1.24/1000 person-yr) and in IBS patients with no
      alosetron use (0.92/1000 person-yr). CONCLUSIONS: Alosetron users did not differ
      from IBS patients not using alosetron in the incidence of bowel surgery or
      hospitalized complications of constipation; there were no cases of colonic
      ischemia. The statistical upper limit of colonic ischemia rates in alosetron
      users was 2.28/1000 person-yr. Because of the market withdrawal, the size of the
      cohort and the duration of follow-up were smaller than originally planned;
      consequently, the statements about the safety of alosetron were necessarily
      limited. On June 7, 2002, the Food and Drug Administration approved alosetron for
      reintroduction in the U.S. market for women with severe diarrhea-related IBS.

PMID- 12809838
TI  - Automated quantitative analysis of nocturnal jejunal motor activity identifies
      abnormalities in individuals and subgroups of patients with slow transit
      constipation.
AB  - OBJECTIVE: Small bowel dysmotility has previously been demonstrated in some
      patients with slow transit constipation (STC), suggesting a generalized
      intestinal disorder. However, no study has addressed whether the incidence of
      small intestinal dysfunction differs between subgroups of patients in this
      heterogeneous population. Using appropriate methodology, we aimed to determine
      prospectively the proportion of individuals with abnormal small bowel motility,
      and to assess whether heterogeneity in terms of pattern of colonic transit delay
      (based on (111)In diethylene-triamine-pentaacetic acid (DTPA) isotope
      scintigraphy), or mode of onset (based on clinical history) is of importance.
      METHODS: Thirty-seven patients with STC underwent 24-h ambulatory jejunal
      manometry; data were compared with those obtained in 38 healthy controls.
      Automated quantitative analysis of seven variables of the nocturnal migrating
      motor complex was performed, to assess whether differences existed between
      groups, and whether individual patients had evidence of small intestinal
      dysmotility, defined as two or more measures of migrating motor complex variables
      outside the normal range. Four variables differed significantly between STC
      patients and controls: in phase III, propagation was slower, duration was longer,
      and contraction amplitude was higher; in phase II, contraction frequency was
      increased. Seven of 24 patients with a generalized pattern of colonic transit
      delay had abnormal small bowel motility compared with none of 13 with a left
      sided delay (p < 0.04). These included four patients with chronic idiopathic
      symptoms and three with acquired symptoms. Approximately one third of patients
      with a generalized delay in colonic transit had evidence of jejunal enteric
      neuromuscular dysfunction. Individual patients with a left-sided colonic delay
      did not satisfy the criteria for nocturnal small bowel dysmotility, but as a
      group, some differences were noted from controls. In contrast to previous
      reports, evidence of generalized enteric dysmotility may be present irrespective
      of the mode of onset.

PMID- 12809839
TI  - Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C.
AB  - OBJECTIVES: Hepatic steatosis (HS) has been related to obesity and fibrosis in
      chronic hepatitis C (CHC). The aim of this study was to determine the role of
      leptin system in HS development. METHODS: Patients (n = 131) with biopsy-proven
      CHC, positive HCV RNA, and raised ALT were enrolled. Body mass index, percentage
      of body fat by skin fold measurement, and bioelectrical impedance analysis was
      calculated and serum leptin concentration measured. Intrahepatic HCV RNA, HS,
      necroinflammatory activity, and fibrosis were determined in liver biopsy tissue.
      RESULTS: HS was present in 63 patients (48.1%). Steatosis was evident in 32 of 91
      patients (35.2%) infected with genotype 1 and in 22 of 27 patients (81.5%) with
      genotype 3a (p < 0.001). In patients infected by genotype 3a, HS correlated
      significantly with intrahepatic HCV RNA load (r = 0.78; p < 0.001). However, in
      genotype 1, HS was associated with host factors such as leptin, body mass index,
      percentage of body fat, and visceral obesity. Multivariate analysis showed
      genotype (OR = 11.54, 95% CI = 1.13-117.14, p = 0.038), leptin levels (OR = 1.09,
      95% CI = 1.03-1.17, p = 0.008) and fibrosis (OR = 9.86, 95% CI = 2.11-5.86, p =
      0.03) as independent variables of HS development. CONCLUSIONS: Hepatic steatosis
      was related to genotype, fibrosis degree, and serum leptin levels. Genotype 3
      seems to have a viral specific steatogenic effect. Leptin seems to be a link
      between obesity and steatosis development in CHC genotype 1-infected patients.

PMID- 12809840
TI  - Hepatic metallothionein in patients with chronic hepatitis C: relationship with
      severity of liver disease and response to treatment.
AB  - OBJECTIVES: Reactive oxygen species may be involved in the pathogenesis of
      chronic hepatitis C virus infection. Metallothionein (MT) is an essential protein
      for the protection of cells against reactive oxygen species. The aim of this
      prospective study was to assess the influence of the hepatic level and cellular
      distribution of MT in hepatitis C virus (HCV) infection and in the liver disease
      outcome. METHODS: In liver biopsy samples of 32 patients with chronic HCV
      infection and of 12 control subjects, quantification of MT was performed by
      radioimmunoassay, MT, interleukin (IL)-1 and -6, and tumor necrosis factor (INF)
      alpha mRNA by reverse transcription-polymerase chain reaction (PCR) and cellular
      distribution by immunohistochemistry. RESULTS: In HCV-infected patients, MT liver
      protein level was 3-fold lower than in control specimens. A significant inverse
      linear regression between MT protein or mRNA expression and the Histological
      Activity Index, the necroinflammatory grade, and the stage of fibrosis was
      observed. MT immunostaining was located in the nucleus and cytoplasm in
      hepatocytes of control subjects, whereas it was mainly cytoplasmic in HCV
      infected patients. Before interferon (IFN) therapy, the hepatic MT level in
      patients that were nonsustained responders was half that of sustained responders.
      Intrahepatic IL-6 and MT were simultaneously down-regulated, but no correlation
      was found between MT and intrahepatic cytokine mRNA expression in patients with
      chronic HCV infection. CONCLUSIONS: This study shows that hepatic MT expression
      could reflect the severity of chronic HCV infection and could be one of the
      factors associated with a favorable clinical outcome in the response to
      interferon therapy.

PMID- 12809841
TI  - Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma
      viral load, steatosis, and liver fibrosis.
AB  - OBJECTIVES: A relationship between chronic hepatitis C virus (HCV) infection and
      lipid metabolism has recently been suggested. The aim of this study was to
      determine the correlation between lipid profile and virology, histologic lesions,
      and response to alpha interferon therapy in noncirrhotic, nondiabetic patients
      with hepatitis C. METHODS: A total of 109 consecutive untreated chronic hepatitis
      C patients were studied to assess the following: 1) the effects of HCV genotype,
      viral load, steatosis, hepatic fibrosis, and body mass index (BMI) on lipid
      profile; and 2) whether lipid parameters could predict response to antiviral
      therapy. RESULTS: The control group showed a significantly higher apolipoprotein
      B (apoB) concentration compared with patients with chronic hepatitis C.
      Hypobetalipoproteinemia (apo B <0.7 g/L) was found in 27 (24.7%) chronic HCV
      patients and in five (5.3%) control subjects (p = 0.0002). Levels of apo B were
      negatively correlated with steatosis and HCV viral load (r = -0.22; p = 0.03).
      This last correlation was strong for non-1 genotype and genotype 3 (r = -0.48; p
      = 0.0005, and r = -0.47; p = 0.007, respectively) but was not found in genotype
      1. In multivariate analysis, low apo B concentration was significantly associated
      with fibrosis grade 2 or 3 versus grade 0 or 1 (p < 0.001), steatosis >5% (p <
      0.001), low body mass index (p < 0.001), and high HCV viral load (p < 0.014). No
      correlation was found in the 76 treated patients between apo B and response to
      interferon therapy. CONCLUSIONS: In chronic HCV patients, hypobetalipoproteinemia
      occurs already in the early stages of HCV infection before the development of
      liver cirrhosis. The correlation between apo B levels and HCV viral load seems to
      confirm the interaction between hepatitis C infection and beta-lipoprotein
      metabolism.

PMID- 12809842
TI  - Is there a role for liver biopsy in primary sclerosing cholangitis?
AB  - OBJECTIVE: Liver biopsies are performed in patients with primary sclerosing
      cholangitis (PSC) to stage disease and to rule out coexisting liver disease. The
      purpose of this study was to examine how often routine liver biopsies provide
      important information in patients with PSC. METHODS: We reviewed the charts of
      138 patients with a cholangiographic diagnosis of PSC to determine whether
      information from liver biopsy had an impact on clinical management. RESULTS: A
      total of 30 patients did not have a liver biopsy, whereas 29 patients had a
      biopsy before cholangiography. In 79 patients the liver biopsy was performed
      after the diagnosis of PSC was established by cholangiography (median time from
      cholangiography to liver biopsy, 21 days). In 78 of 79 patients (98.7%) the liver
      biopsy revealed no atypical findings and did not affect clinical management. In
      one patient the liver biopsy revealed findings of an overlap syndrome with
      autoimmune hepatitis, and the patient was treated with corticosteroids and
      azathioprine. This patient had biochemical features consistent with autoimmune
      hepatitis. One patient developed a bile leak after liver biopsy, requiring
      hospitalization (complication rate 0.9%). CONCLUSIONS: Liver biopsies rarely
      contribute new information that affects the management of patients with PSC.
      Given the risks of the procedure, liver biopsies for patients with a diagnosis of
      PSC established by cholangiography may not routinely be necessary.

PMID- 12809843
TI  - Comparison of three commercially available assays for HCV RNA using the
      international unit standard: implications for management of patients with chronic
      hepatitis C virus infection in clinical practice.
AB  - OBJECTIVES: The present study was performed to evaluate the impact of the
      international unit standard for measuring HCV RNA in the management of patients
      with chronic hepatitis C virus (HCV) infection. METHODS: The three assays used
      were Amplicor Monitor PCR, the National Genetics Institute PCR assay, and
      branched chain DNA. HCV RNA was measured at four time points (baseline, 3 months
      after the start of therapy, at the end of treatment, and 6 months after
      discontinuation of therapy) in 106 consecutive patients who received interferon
      and ribavirin for chronic HCV. RESULTS: The mean age of the patients was 44 yr.
      Of the patients, 62% were male, 24% were African American, 38% had bridging
      fibrosis or cirrhosis, and 75% were HCV genotype 1. Of the 424 samples analyzed,
      82-89% of values were within 1 log unit and 85-92% were within 2 log units by the
      various assays. This variability was not dependent upon HCV genotype. HCV RNA was
      undetectable in 1.4-6.8% of samples when virus was detected by another assay. The
      mean HCV RNA in these discordant samples was 1.47-6.33 log IU/ml (30-2,100,000
      IU/ml). CONCLUSIONS: These data demonstrate that approximately 90% of serum
      values for HCV RNA were within 1 log unit by the international unit standard
      regardless of which virological assay was used. However, false positive and false
      negative results as well as variations in the HCV RNA level of more than 1 to 2
      log units can occur with any of the assays, and these results may have an impact
      upon the management of patients receiving interferon therapy. It is therefore
      unwise in clinical practice to base important treatment decisions upon a single
      HCV RNA determination.

PMID- 12809844
TI  - Comparison of MELD, Child-Pugh, and Emory model for the prediction of survival in
      patients undergoing transjugular intrahepatic portosystemic shunting.
AB  - OBJECTIVES: Recently, new prognostic models (Model for End-Stage Liver Disease
      [MELD model] and Emory score) were proposed for the prediction of survival in
      transjugular intrahepatic portosystemic shunt (TIPS) patients. Although the MELD
      model is considered to be superior and has consecutively been applied to priority
      listing for liver transplantation, these models have never been directly compared
      in terms of long-term prognosis. We therefore compared the prognostic accuracy of
      the different models, including the Child-Pugh score, in an unselected cohort of
      TIPS patients followed long-term. METHODS: Baseline risk scores for 162
      unselected consecutive TIPS patients followed until death (n = 81), liver
      transplantation, or end of observation (n = 81) (mean follow-up 30.7 +/- 26.4
      months) were calculated, and respective concordance- (c-)statistics for the
      predictive accuracy of 3-, 12-, and 36-month survival for the three models were
      compared statistically. RESULTS: All three models predicted short-term (3-month)
      survival with similar accuracy. The MELD model generated the best c-statistics
      for both 12-month (c-statistic 0.73, 95% CI = 0.64-0.82) and 36-month survival (c
      statistic 0.74, 95% CI = 0.64-0.84). The predictive accuracy of the Emory score
      was significantly lower (c-statistic for 12-month survival: 0.60, 95% CI = 0.52
      0.68, p = 0.012 vs MELD). In the statistical comparison of the MELD and the Child
      Pugh model, only a trend favoring MELD for the prediction of 1-yr survival in
      patients with intestinal bleeding could be observed (MELD: c-statistic 0.78, 95%
      CI = 0.67-0.89; Child-Pugh: c-statistic 0.67, 95% CI = 0.55-0.80, p = 0.059).
      CONCLUSIONS: The MELD model is superior to the Emory score but only slightly
      superior to the Child-Pugh classification for the prediction of long-term
      survival in TIPS patients.

PMID- 12809845
TI  - Insurance, employment, and psychosocial consequences of a diagnosis of hereditary
      hemochromatosis in subjects without end organ damage.
AB  - OBJECTIVES: Asymptomatic individuals with hereditary hemochromatosis (HH) may
      experience difficulties in obtaining employment or insurance, despite their good
      health. The extent to which these difficulties occur is unclear. The aim of this
      study was to assess the insurance, employment, and psychosocial consequences of a
      diagnosis of HH in subjects with no end organ damage. METHODS: In three
      outpatient clinics specializing in the treatment of HH, we performed a survey of
      individuals diagnosed with HH who were without end organ damage secondary to iron
      overload, along with their unaffected siblings. A review of the medical records
      of subjects with HH was performed. Main outcomes were attaining and keeping
      employment; health, disability and life insurance; and scores on the SF-36, a
      quality of life measure, and the SCL-90-R, a measure of psychological well-being.
      RESULTS: Of 130 eligible subjects with HH, 126 (97%) responded. Of the 55
      eligible controls, 46 (84%) responded. Of the 126 subjects with HH, 25 (20%)
      described 28 incidents of insurance denial or increased premium rates, which they
      attributed to their diagnosis HH. Of the 28 incidents, 16 (57%) involved life
      insurance, eight (29%) involved health insurance, and four (14%) involved
      disability insurance. One subject reported an employment refusal. Five of the 25
      subjects (20%) reporting insurance denial or increased premiums had significant
      comorbid conditions. One of 46 sibling controls (2%) reported an increased rate
      for life insurance (p = 0.003). No differences were noted in either the SF-36 or
      the SCL-90-R scores between subjects with HH and unaffected siblings. Overall
      rates of active health, disability, and life insurance were similar between the
      groups. CONCLUSIONS: Insurance denial and increased premium rates are reported
      commonly among individuals with HH without end organ damage. However, the overall
      proportion of those with active insurance, the quality of life, and the
      psychological well-being of these subjects were similar to those of unaffected
      siblings.

PMID- 12809846
TI  - Transarterial chemoembolization for inoperable, early stage hepatocellular
      carcinoma in patients with Child-Pugh grade A and B: results of a comparative
      study in 96 Chinese patients.
AB  - OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation
      of survival is controversial. We conducted a comparative study to determine
      whether TACE treatment had any survival benefit for patients with unresectable
      hepatocellular carcinoma (HCC) and with relatively preserved liver function.
      METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and
      Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who
      received TACE were compared to 16 patients (group 2) who were treated
      conservatively. RESULTS: The median survival time of group 1 patients was
      significantly longer than that of group 2 patients (31.2 vs 14.1 months
      respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr,
      3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5%
      (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5%
      versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor
      response was observed in 28% of patients receiving TACE. Patients with higher
      pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and
      Okuda stage I disease were associated with a favorable response to TACE.
      CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in
      the early stages and with relatively preserved liver function.

PMID- 12809847
TI  - Survival of colorectal cancer patients hospitalized in the Veterans Affairs
      Health Care System.
AB  - OBJECTIVES: A recent analysis based on data from the Surveillance, Epidemiology,
      and End Results (SEER) Program of the National Cancer Institute indicates that no
      survival benefit occurred, for white or for black individuals, in colorectal
      cancer diagnosed during 1986-1997, and that blacks fared worse than whites. The
      objective of this research was to evaluate recent temporal trends in the survival
      of patients with colorectal cancer admitted to hospitals in the Veterans Affairs
      (VA) system, which offers equal access to care and facilitates systemwide
      implementation of prevention and treatment services. METHODS: This research was a
      cohort study of patients admitted to all VA hospitals with a new diagnosis of
      colorectal cancer between October, 1987, and September, 1998, and followed
      through September, 2001. Temporal changes in observed 5-yr survival were
      evaluated for the periods 1987-1989, 1990-1992, 1993-1995, and 1996-1998.
      Cumulative survival was obtained from Kaplan-Meier estimates, whereas adjusted
      risk of death was calculated using a Cox proportional hazards model. Adjustment
      was made for differences in patient characteristics, including comorbidity.
      RESULTS: We identified 46,044 individuals with colorectal cancer in VA hospitals
      during 1987-1998, 98.5% of whom were men. The mean age was 67.7 yr, and the two
      largest racial/ethnic groups were whites (76.5%) and blacks (17.1%). Significant
      differences in survival were seen over time (p < 0.001, log rank test) with
      longer survival in patients diagnosed in the more recent time periods. In the
      multivariable Cox model, survival showed an 18% increase over time (1987-1998)
      after adjusting for differences in age, race, comorbidity, cancer site, and
      extent of disease. There was a small but statistically significant decrease in
      chance of survival in blacks compared with whites (adjusted relative survival
      0.96, 95% CI = 0.92-0.99). CONCLUSIONS: Recent non-VA studies have shown stable
      survival for colorectal cancer patients over time, coupled with significantly
      decreased survival for blacks compared with whites. In contrast, in the VA
      system, survival has improved for both white and black patients; in addition, the
      racial discrepancy in survival is markedly attenuated. These results suggest that
      the benefits of prevention and treatment advances may be more readily achieved in
      the VA's equal access, integrated health care system.

PMID- 12809848
TI  - P53 protein and malignant progression in Barrett's metaplasia (Barrett's
      esophagus).

PMID- 12809850
TI  - Re: Laine and Sugg-Helicobacter pylori eradication on esophagitis and GERD.

PMID- 12809852
TI  - Over-the-counter nonsteroidal anti-inflammatory drugs and risk of
      gastrointestinal symptoms.

PMID- 12809854
TI  - Ulcerating proctitis in a patient with congenital neutropenia.

PMID- 12809855
TI  - The end of Helicobacter pylori as a hypothetic cause of SIDS.

PMID- 12809856
TI  - Successful treatment of steroid resistant ulcerative colitis associated with
      severe autoimmune hemolytic anemia with oral microemulsion cyclosporin--a brief
      case report.

PMID- 12809857
TI  - Plummer-Vinson syndrome associated with celiac disease and complicated by
      postcricoid carcinoma and carcinoma of the tongue.

PMID- 12809858
TI  - Acute hyperkalemia associated with intravenous omeprazole therapy.

PMID- 12809859
TI  - Acute pancreatitis may precede the clinical manifestations of Crohn's disease.

PMID- 12809860
TI  - Compression of liver parenchyma by a malignant hepatic cyst: a previously
      unreported manifestation of metastatic gastric cancer.

PMID- 12809861
TI  - The low prevalence of helicobacter infection in patients with inflammatory bowel
      disease could be attributed to previous antibiotic treatment.

PMID- 12809862
TI  - Chili pepper and rectal hyperalgesia in irritable bowel syndrome.

PMID- 12809863
TI  - Combined lamivudine and interferon-alpha therapy for chemotherapy-induced
      reactivation of hepatitis B virus.

PMID- 12809865
TI  - Nitric oxide and the lower urinary tract: current concepts, future prospects.

PMID- 12809866
TI  - Comparison of lower urinary tract symptom severity and associated bother between
      community-dwelling black and white men: the Olmsted County Study of Urinary
      Symptoms and Health Status and the Flint Men's Health Study.
AB  - OBJECTIVES: To determine the magnitude of racial disparity in lower urinary tract
      symptom (LUTS) severity and bother by combining two large comparable
      epidemiologic studies of community-dwelling white and black men, thereby avoiding
      many of the referral biases present in previous studies. Prior studies evaluating
      racial differences in benign prostatic hyperplasia have been hampered by
      selection bias, because nearly all have used surgical treatment as a marker for
      benign prostatic hyperplasia. METHODS: Data from the Olmsted County Study of
      Urinary Symptoms and Health Status and the Flint Men's Health Study were combined
      for a total study sample of 2480 men. We examined LUTS severity and associated
      bother as measured by the self-administered American Urological Association
      Symptom Index and Symptom Problem Index. RESULTS: Overall 34% of white men
      reported moderate/severe LUTS compared with 41% of black men (P <0.001). These
      patterns were consistent across age and persisted after adjustment for age and
      other sociodemographic factors. The relationship between LUTS severity and bother
      differed by race in that black men reported less bother for each unit increase in
      LUTS (P <0.001). CONCLUSIONS: In contrast to studies based on clinical
      populations, our community-based study demonstrated greater LUTS severity in
      black men compared with white men but black men reported less bother for any
      given level of LUTS severity. Although these findings suggest a racial disparity
      in benign prostatic hyperplasia, additional studies of anatomic, physiologic, and
      molecular factors may clarify whether these racial differences are real or due to
      sociocultural differences in reporting symptom morbidity.

PMID- 12809867
TI  - Variability of renal stone fragility in shock wave lithotripsy.
AB  - OBJECTIVES: To measure, in an in vitro study, the number of shock waves to
      complete comminution for 195 human stones, representing six major stone types.
      Not all renal calculi are easily broken with shock wave lithotripsy. Different
      types of stones are thought to have characteristic fragilities, and suggestions
      have been made in published reports of variation in the fragility within some
      types of stones, but few quantitative data are available. METHODS: Kidney stones
      classified by their dominant mineral content were broken in an unmodified Dornier
      HM3 lithotripter or in a research lithotripter modeled after the HM3, and the
      number of shock waves was counted for each stone until all fragments passed
      through a sieve (3-mm-round or 2-mm-square holes). RESULTS: The mean +/- SD
      number of shock waves to complete comminution was 400 +/- 333 per gram (n = 39)
      for uric acid; 965 +/- 900 per gram (n = 75) for calcium oxalate monohydrate;
      1134 +/- 770 per gram (n = 21) for hydroxyapatite; 1138 +/- 746 per gram (n = 13)
      for struvite; 1681 +/- 1363 per gram (n = 23) for brushite; and 5937 +/- 6190 per
      gram (n = 24) for cystine. The variation for these natural stones (83% +/- 15%
      coefficient of variation) was greater than that for artificial (eg, gypsum-based)
      stones (17% +/- 8%). CONCLUSIONS: The variability in stone fragility to shock
      waves is large, even within groups defined by mineral composition. Thus, knowing
      the major composition of a stone may not allow adequate prediction of its
      fragility in lithotripsy treatment. The variation in stone structure could
      underlie the variation in stone fragility within type, but testing of this
      hypothesis remains to be done.

PMID- 12809869
TI  - Cytologic detection of human papillomavirus DNA in normal male urethral samples.
AB  - OBJECTIVES: To quantify the existence of human papillomavirus (HPV) infection
      without detectable lesions in the male urethra, and to verify the sensitivity and
      specificity of ureteral cytology. We compared the results of clinical and
      colposcopic examinations, ureteral cytology, and HPV DNA testing by polymerase
      chain reaction amplification in the male partners of women with genital HPV
      disease. METHODS: A total of 110 cytobrush samples of urethral cells from male
      sexual partners of women with genital HPV-associated lesions were analyzed by
      cytology and for virologic detection of HPV 6/11, 42, 16/18 by polymerase chain
      reaction followed by Southern blot hybridization. The results were correlated
      with the presence or absence of genital HPV-associated lesions. RESULTS: HPV DNA
      was detected in 1 sample (3%) from men without visible lesions, in 5 samples
      (15%) from men with penile lesions but without urethral lesions, and in 16 men
      with urethral lesions (78%). Cytology showed cellular changes suggesting HPV
      infection in 81% of men with urethral lesions, but also in 15% of men without
      lesions. CONCLUSIONS: Our results show that HPV-DNA positivity in the absence of
      clinically or colposcopically detected lesions is a rare event. Although
      sensitive enough, cytology is not specific, and its use as a screening tool may
      lead to a high number of false-positive results.

PMID- 12809870
TI  - Prospective study of the effects of shock wave lithotripsy on renal function:
      role of post-shock wave lithotripsy obstruction.
AB  - OBJECTIVES: To examine the effects of transient post-shock wave lithotripsy (SWL)
      obstruction on renal function after SWL application for treatment of renal stones
      in nonobstructed kidneys. METHODS: One hundred consecutive patients with
      unilateral renal stones were treated by SWL monotherapy. They had a normal
      laboratory profile and no or controlled urinary tract infection. The urinary
      tract was radiologically normal. Technetium-99m mercaptoacetyltriglycine and
      Doppler ultrasonography were performed for all cases a few days before and 1 week
      and 3 months after SWL. Renal uptake, time to peak clearance, split renal
      function, effective renal plasma flow, and resistive index were obtained.
      Patients were stratified into two groups. Group 1 consisted of patients with
      normal kidneys before SWL and unobstructed kidneys after SWL (n = 84). Group 2
      consisted of patients with normal kidneys before SWL that were obstructed 1 week
      after SWL (n = 16). RESULTS: In group 1, there was a gradual increase in the
      effective renal plasma flow that became significant after 3 months, up to 114% of
      the pretreatment levels (P = 0.008). The glomerular filtration rate was stable 1
      week after SWL and had increased significantly after 3 months, up to 110% of the
      pretreatment levels (P = 0.006). In group 2, there was marked deterioration of
      the effective renal plasma flow and glomerular flow rate to 50.5% (P = 0.002) and
      45.8% (P = 0.001), respectively, of the pretreatment levels. These levels
      returned to the basal levels after 3 months. No significant changes occurred in
      the resistive index in both groups. CONCLUSIONS: Extracorporeal shock wave
      lithotripsy has no deleterious effects on the renal function. Post-SWL
      obstruction, although transient, has a major effect on the renal function on the
      treated side and must be managed urgently.

PMID- 12809872
TI  - Impact of hydronephrosis and renal function on treatment outcome: antegrade
      versus retrograde endopyelotomy.
AB  - OBJECTIVES: To compare, in a single-surgeon, single-institution study, the
      efficacy of antegrade and retrograde endopyelotomy in terms of success rate and
      morbidity and to identify which risk factors affect treatment outcomes. METHODS:
      The results were retrospectively reviewed for 88 patients with ureteropelvic
      junction obstruction treated with endopyelotomy. Antegrade endopyelotomy was
      performed with a hook knife, scissors, or cutting balloon device. Retrograde
      endopyelotomy was performed with a cutting balloon device. Objective results were
      based on intravenous urogram and/or diuretic nuclear renal scan findings, and
      subjective results were based on direct patient query and questionnaire. RESULTS:
      Ninety-three endopyelotomy procedures, 64 antegrade and 29 retrograde, were
      performed. The mean follow-up was 37.0 months (range 5 to 76). The overall
      success rates between antegrade and retrograde endopyelotomy (81.3% versus 75.9%)
      were not statistically different (P = 0.553). Patients with massive
      hydronephrosis and poor initial renal function were less likely to have
      successful endopyelotomy. Antegrade endopyelotomy, however, was more successful
      than retrograde endopyelotomy in patients with massive hydronephrosis (66.7%
      versus 20.0%; P = 0.046). The average operative time for antegrade and retrograde
      endopyelotomy was 93.9 and 32.7 minutes (P <0.001), respectively. The average
      length of hospital stay after antegrade and retrograde endopyelotomy was 3.20 and
      0.14 nights (P <0.001), respectively. CONCLUSIONS: Both antegrade and retrograde
      endopyelotomy are effective treatments for ureteropelvic junction obstruction
      associated with minimal morbidity. Antegrade endopyelotomy appears to be more
      successful in patients with high-grade hydronephrosis. Retrograde endopyelotomy
      results in a shorter hospital stay, a shorter operative time, and less
      postoperative pain.

PMID- 12809874
TI  - Electrical prostate morcellator: an alternative to manual morcellation for
      laparoscopic nephrectomy specimens? An in vitro study.
AB  - OBJECTIVES: To compare the safety and efficacy of morcellation with the
      electrical prostate morcellator (EPM) or manual morcellation of the kidney, using
      an internal view within the morcellation sac. METHODS: Thirty porcine kidneys,
      mean renal mass 174.5 g, were divided into three groups of 10. All morcellations
      were performed inside the LapSac. Groups 1 and 2 underwent morcellation using the
      EPM, monitored inside the LapSac using the nephroscope and outside the LapSac
      with the laparoscope, respectively. Group 3 underwent manual morcellation with
      ring forceps. The groups were assessed for morcellation time, fragment size, and
      LapSac integrity. RESULTS: In group 1, one pinhole perforation occurred; in group
      2, nine perforations occurred (five large and four pinhole). No perforations
      occurred (P <0.001) in group 3 (manual morcellation). The mean morcellation time
      for groups 1 through 3 was, respectively, 86.9, 47.1, and 15.1 minutes (P
      <0.0001). The corresponding mean fragment size was 0.011, 0.015, and 1.36 g. The
      difference in mean fragment size was significantly different between the manual
      morcellation group and the EPM groups (P <0.001), but not between the two EPM
      groups (P = 0.12). CONCLUSIONS: Manual morcellation was safe, fast, and superior
      to morcellation with the EPM monitored either inside or outside the LapSac. The
      high rate of LapSac perforation precludes the use of EPM after laparoscopic
      radical nephrectomy in the clinical forum.

PMID- 12809877
TI  - American Urological Association Symptom Index for lower urinary tract symptoms in
      women: correlation with degree of bother and impact on quality of life.
AB  - OBJECTIVES: To determine first whether the American Urological Association
      Symptom Index (AUASI) correlates with the degree of bother caused by lower
      urinary tract symptoms (LUTS) in women and whether the association varies with a
      woman's age and continent status; and second, whether the AUASI and degree of
      bother caused by symptoms correlate with a woman's quality of life (QOL) and
      whether the association varies with a woman's age and continent status. LUTS
      occur in women and may produce significant bother and affect their QOL. The AUASI
      has been used to evaluate LUTS in female patients; however, its correlation with
      the degree of bother and QOL has not been clearly established in women. METHODS:
      The charts of 1232 women who completed the AUASI, as well as the Symptom Problem
      Index and global QOL question, were reviewed. Spearman's rank order correlation
      was computed to assess the correlation between the AUASI and Symptom Problem
      Index. It was also computed after stratifying the women's age and continence
      status (continent versus incontinent). A linear regression model was applied,
      with the AUASI and Symptom Problem Index as the response variables and QOL as the
      continuous explanatory variable. RESULTS: The mean age was 54.6 years. Six
      hundred women (49%) were incontinent. Spearman's rank order showed a strong
      correlation between symptoms and problems caused by symptoms (0.858, P <0.0001).
      The correlation existed throughout various age groups and was independent of
      coexisting incontinence. The symptoms correlated with QOL in a similar pattern.
      CONCLUSIONS: The AUASI accurately described LUTS in women and, as with men, is a
      good indicator of the degree of bother and affect on QOL.

PMID- 12809878
TI  - Estimated economic costs of overactive bladder in the United States.
AB  - OBJECTIVES: To estimate the economic costs of overactive bladder (OAB), including
      community and nursing home residents, and to compare the costs in male versus
      female and older versus younger populations. METHODS: The National Overactive
      Bladder Evaluation Program included a representative telephone survey of 5204
      community-dwelling adults 18 years and older in the United States and a follow-up
      postal survey of all individuals with OAB identified and age and sex-matched
      controls. The postal survey asked respondents about bladder symptoms, self-care
      use, treatment use, work loss, and OAB-related health consequences. Survey data
      estimates were combined with year 2000 average cost data to calculate the cost of
      OAB in the community. Institutional costs were estimated from the costs of
      urinary incontinence in nursing homes, limited to only those with urge
      incontinence or mixed incontinence (urge and stress). RESULTS: The estimated
      total economic cost of OAB was 12.02 billion dollars in 2000, with 9.17 and 2.85
      billion dollars incurred in the community and institutions, respectively.
      Community female and male OAB costs totaled 7.37 and 1.79 billion dollars,
      respectively. The estimated total cost was sensitive to the estimated prevalence
      of OAB; therefore, we calculated the average cost per community-dwelling person
      with OAB, which was 267 dollars per year. CONCLUSIONS: By quantifying the total
      economic costs of OAB, this study-the first obtained from national survey data
      provides an important perspective of this condition in society. The conservative
      estimates of the total cost of OAB were comparable to those of osteoporosis and
      gynecologic and breast cancer. Although this provides information on the direct
      and indirect costs of OAB, quality-of-life issues must be taken into account to
      gain a better understanding of this condition.

PMID- 12809879
TI  - Endorectal coil magnetic resonance imaging for diagnosis of urethral and
      periurethral pathologic findings in women.
AB  - OBJECTIVES: To report our experience with endorectal coil magnetic resonance
      imaging (ERC-MRI) in the evaluation of female patients with lower urinary tract
      symptoms (LUTS). We present the results of symptomatic patients who underwent
      this imaging modality, to better define its use and to try to identify
      applications relevant to everyday clinical practice. METHODS: We reviewed
      retrospectively 140 consecutive patients who presented with LUTS and underwent
      ERC-MRI between June 1997 and June 2000. Assessment included history, physical
      examination, urodynamic studies, and other radiologic evaluations (such as
      voiding cystourethrogram). Patients were divided into five groups on the basis of
      the main indication for ordering the MRI. The results in the subgroups of
      patients who had repeat ERC-MRI and transvaginal urethrolysis were also analyzed.
      RESULTS: Findings consistent with periurethral fibrosis were detected in 52% of
      the patients, most frequently in those with symptoms suggestive of, or with
      urodynamic evidence of, obstruction. Ten percent of the patients were found to
      have urethral diverticula; in 54% of this group, the diagnosis was made solely by
      MRI. Repeat ERC-MRI showed either periurethral fibrosis or a urethral
      diverticulum in most patients (17 of 22). No correlation was observed between the
      subjective estimate of scar tissue during urethrolysis and the amount determined
      by the interpretation of the images. CONCLUSIONS: Our 3-year experience suggests
      that ERC-MRI may help better define the diagnosis of urethral and periurethral
      pathologic features in female patients with LUTS. With improved patient
      selection, ERC-MRI will likely have a role in evaluating women with symptoms
      difficult to explain by other diagnostic modalities.

PMID- 12809882
TI  - Value of express T2-weighted pelvic MRI in the preoperative evaluation of severe
      pelvic floor prolapse: a prospective study.
AB  - OBJECTIVES: To report our prospective experience with extended-phase conjugate
      symmetry rapid spin-echo sequence (EXPRESS) magnetic resonance imaging (MRI) of
      the female pelvis in the preoperative staging of severe pelvic floor prolapse
      (PFP). Severe PFP represents a significant diagnostic and reconstructive
      challenge for clinicians. Although the clinical utility of dynamic MRI has
      already been demonstrated, EXPRESS MRI has not been prospectively studied in the
      evaluation of PFP. METHODS: Between January 1999 and December 2001, 31
      consecutive female patients with severe PFP were referred to our institution.
      Twenty of them underwent EXPRESS dynamic pelvic MRI. The physical examination,
      MRI, and intraoperative findings were statistically correlated. RESULTS: The mean
      age of the 20 patients undergoing preoperative EXPRESS MRI was 67 years. The mean
      duration of prolapse was 6.1 years. All 20 patients underwent surgery for
      symptomatic PFP with or without associated voiding dysfunction. No postoperative
      complications or recurrent PFP had occurred at a median follow-up of 19 months.
      Significant correlations were found between the preoperative pelvic examination
      findings and operative findings of cystourethrocele and vaginal cuff prolapse,
      and significant correlations were found between MRI findings and operative
      findings of enterocele, cystourethrocele, vaginal cuff prolapse, and uterine
      prolapse. CONCLUSIONS: EXPRESS MRI can accurately stage PFP. The technique is
      rapid, precise, and noninvasive. Practitioners should consider obtaining dynamic,
      rapid-sequence sagittal pelvic MRI scans in cases of severe PFP when the
      diagnosis is not clear before surgery. More accurate preoperative information may
      ultimately result in improved long-term surgical outcomes and guide the
      refinement of surgical techniques.

PMID- 12809883
TI  - Association of p53 and p21 expression with clinical outcome in patients with
      carcinoma in situ of the urinary bladder.
AB  - OBJECTIVES: To determine whether p53 and p21 expression in bladder carcinoma in
      situ (CIS) with or without papillary disease can predict disease recurrence,
      progression, and survival. METHODS: Immunohistochemical staining for p53 and p21
      was carried out on paraffin-embedded tumor specimens from 47 and 39 patients,
      respectively, who had CIS with or without Ta or T1 disease, but without muscle
      invasive cancer. Immunoreactivity was categorized as either positive (reactivity
      in 10% or more CIS cells) or negative. RESULTS: Expression of p53 and p21 was
      positive in 28 (60%) of 47 and 12 (31%) of 39 CIS tumors, respectively. p53
      expression was not associated with clinical outcome. Positive p21 expression was
      associated with bladder cancer recurrence (P = 0.035) and progression (P = 0.033)
      when adjusted for the effects of clinical stage and grade. The combined p53/p21
      expression status was independently associated with disease recurrence (P =
      0.022), progression (P = 0.042), and cancer-specific survival (P = 0.031).
      Patients with p53+/p21+ expression were at significantly greater risk of disease
      recurrence, progression, and mortality than those having a p53+/p21- or p53-/p21-
      phenotype (not significantly different from each other statistically).
      CONCLUSIONS: In CIS without muscle-invasive disease, positive p21 expression was
      independently associated with bladder cancer recurrence and progression. Positive
      expression for both p53 and p21 puts patients with bladder CIS at the greatest
      risk of bladder cancer recurrence, progression, and, most importantly, mortality,
      suggesting a potential rationale for early definitive therapy in these patients.
      On the other hand, an intact pathway at the level of p21 seems to abrogate the
      detrimental effects of altered p53 immunoreactivity on the outcome of bladder
      CIS.

PMID- 12809884
TI  - Cytologic analysis of ureteral washings is informative in patients with grade 2
      upper tract TCC considering endoscopic treatment.
AB  - OBJECTIVES: To determine the diagnostic accuracy of ureteroscopic biopsy and
      whether exfoliated cell cytology can improve diagnostic accuracy. METHODS: Sixty
      two cases of upper tract transitional cell carcinoma were diagnosed by
      ureteroscopic biopsy and treated by nephroureterectomy. Stage and grade
      evaluation was possible in 51 cases. Cytology for exfoliated cells from the
      ureter/pelvis was available in 48 cases. RESULTS: Biopsies were staged as Tis in
      3, Ta in 35, and T1 in 13 and graded as G1 in 6, G2 in 32, and G3 in 13. Cytology
      was positive/suspicious in 40% (19 of 48). The biopsy grade accurately predicted
      the pathologic grade (P <0.0001) and stage (P = 0.001). The biopsy stage was not
      associated with the final stage (P = 0.112, Fisher's exact test). Biopsy G3
      accurately predicted high-grade (G3) transitional cell carcinoma in 92% (12 of
      13) of cases. The remaining 1 case was G2 by final histologic examination. No
      case of high-grade (G3) disease was found in the 6 G1 biopsies (100%). Of 32 G2
      biopsies, 9 were upgraded to G3. Cytology was available for 8 of the 9 and 5
      (63%) were positive. For patients with G2 biopsies, combining cytology and biopsy
      grade improved the sensitivity and specificity of high-grade tumor detection from
      43% to 55% and 23% to 85%, respectively. CONCLUSIONS: The results of this study
      have shown that biopsy grade reflects the pathologic stage and grade. Combining
      exfoliated cell cytology improved the predictive power of biopsy G2 disease for
      high-risk specimen grade. Exfoliated cell cytology in combination with biopsy
      grade is recommended as part of the evaluation of upper tract transitional cell
      carcinoma selected for endoscopic management.

PMID- 12809885
TI  - Clinical presentation and outcome of high-grade urinary bladder leiomyosarcoma in
      adults.
AB  - OBJECTIVES: To determine the clinical presentation and outcome of patients with
      high-grade bladder leiomyosarcoma. METHODS: Between July 1986 and April 1998, 36
      adult patients (mean follow-up 56 months) with a diagnosis of urinary bladder
      leiomyosarcoma were evaluated at the University of Texas M. D. Anderson Cancer
      Center. We retrospectively reviewed the records of these patients for information
      on clinical features, treatment, and outcome. RESULTS: The mean age of the
      patients was 63 years. Twenty-six patients were white men in their seventh
      decade. The most common symptom at presentation was gross hematuria (81% of
      patients), followed by increased urinary frequency (28%), and dysuria (19%).
      Thirty-five patients were treated surgically for bladder leiomyosarcoma; of
      these, 12 (34%) developed recurrent disease (5 with local recurrence and 7 with
      distant metastasis), with a median time to diagnosis of recurrent disease of 8.3
      months. The most common site of distant failure was the retroperitoneum. The
      disease-specific survival rate at 1, 3, and 5 years was 88.6%, 62.0%, and 62.0%,
      respectively. Multivariate analyses demonstrated that only the Memorial Sloan
      Kettering Cancer Center disease stage system was a significant predictor of
      survival of patients with bladder leiomyosarcoma (P = 0.018). CONCLUSIONS: In
      patients with high-grade leiomyosarcoma of the bladder, radical cystectomy in the
      face of localized disease, whether at the initial presentation or after
      neoadjuvant chemotherapy, can result in a 5-year, disease-specific survival rate
      of 62.0%.

PMID- 12809886
TI  - Acupuncture ameliorates symptoms in men with chronic prostatitis/chronic pelvic
      pain syndrome.
AB  - OBJECTIVES: To determine in a pilot study whether acupuncture improved pain,
      voiding symptoms, and the quality of life of men with chronic prostatitis/chronic
      pelvic pain syndrome. METHODS: Men diagnosed with chronic prostatitis/chronic
      pelvic pain syndrome (National Institutes of Health [NIH] criteria) who were
      refractory to standard therapy (antibiotics, alpha-blockers, anti-inflammatories,
      phytotherapy) were referred for acupuncture therapy. The treatment protocol
      involved three sets of acupuncture points totaling 30 points (8 points were
      electrically stimulated) given alternatively twice weekly for 6 weeks. The
      patients completed the NIH Chronic Prostatitis Symptom Index (CPSI) at baseline
      and the CPSI and subjective global assessment at 6 weeks (end of treatment), 12
      weeks, and at least 6 months after the baseline assessment. RESULTS: Twelve men
      underwent a minimum of 6 weeks of acupuncture treatment. The average follow-up
      (from baseline) was 33 weeks (range 24 to 52). A significant decrease occurred in
      total NIH-CPSI (28.2 to 8.5), NIH-CPSI pain (14.1 to 4.8), NIH-CPSI urinary (5.2
      to 1.3), and NIH-CPSI quality-of-life (8.8 to 2.3) scores after an average of 33
      weeks of follow-up. Ten patients (83%) had a sustained greater than 50% decrease
      in NIH-CPSI at final visit (average 33 weeks). Ten patients (83%) reported marked
      improvement on the subjective global assessment at 12 weeks. At an average of 33
      weeks, 8 patients (67%) had sustained marked improvement on subjective global
      assessment evaluation. No adverse events were reported in this pilot study.
      CONCLUSIONS: Acupuncture appears to be a safe, effective, and durable treatment
      in improving symptoms in, and the quality of life of, men with chronic
      prostatitis/chronic pelvic pain syndrome refractory to treatment. A larger
      controlled study is required to confirm these encouraging initial results.

PMID- 12809888
TI  - Cooled thermotherapy for the treatment of benign prostatic hyperplasia:
      durability of results obtained with the Targis System.
AB  - OBJECTIVES: To evaluate the durability of benefit associated with cooled high
      energy thermotherapy (cooled thermotherapy) using the Targis System with data
      extending to 5 years after treatment. METHODS: At three centers in Canada and the
      United Kingdom, 150 patients with benign prostatic hyperplasia underwent cooled
      thermotherapy with the Targis System. This was an outpatient procedure performed
      without general or regional anesthesia. Patients were followed up at 1 and 6
      weeks, 3, 6, and 12 months, and yearly to 5 years. RESULTS: Patients were
      evaluated at 1, 2, 3, 4, and 5 years after treatment (n = 132, 111, 90, 77, and
      59, respectively). At these intervals, the American Urological Association
      symptom scores improved by 11.7 (57%), 12.1 (58%), 11.5 (53%), 10.1 (47%), and
      10.6 (47%) points (P <0.0001 for each), the peak flow rates improved by a mean of
      4.0 (57%), 4.0 (56%), 3.4 (48%), 3.3 (47%) and 2.4 (37%) mL/s (P <0.0001 for
      each), and quality-of-life scores improved by 2.6, 2.6, 2.5, 2.3, and 2.3 points
      (P <0.0001 for each). At least a 50% improvement in the American Urological
      Association symptom score was observed in 63% to 68% of patients available for
      follow-up at years 1, 2, and 3 and 50% and 51% of patients available for follow
      up at years 4 and 5, respectively. Four patients required repeated microwave
      thermotherapy, 27 required subsequent invasive treatments, 1 permanent
      catheterization, 11 required alpha-blockers, and 1 antiandrogen therapy.
      CONCLUSIONS: Cooled thermotherapy with the Targis System produces durable
      improvements in symptoms, quality of life, and flow rates to at least 5 years
      after treatment.

PMID- 12809891
TI  - 5-year outcome of a prospective randomized trial to compare transurethral
      electrovaporization of the prostate and standard transurethral resection.
AB  - OBJECTIVES: To update our prospective randomized trial comparing the safety,
      efficacy, and durability of transurethral electrovaporization of the prostate
      (TUVP) using the VaporTrode with standard transurethral resection of the prostate
      (TURP). METHODS: A total of 104 patients, taken from the waiting list for surgery
      for benign prostatic hyperplasia were randomized to TUVP (52 patients, mean age
      67.5 years) or TURP (52 patients, mean age 70.2 years). In each group, 51, 47,
      and 40 patients completed 1, 2, and 3 years of follow-up, respectively. Of the
      104 patients, 27 TURP and 26 TUVP patients completed 5 years of follow-up.
      RESULTS: Both groups were comparable in terms of the mean preoperative
      International Prostate Symptom Score, quality-of-life score, maximal urinary flow
      rate, and postvoid residual volume. The follow-up data at 5 years showed a
      significant and maintained improvement in the mean International Prostate Symptom
      Score (TUVP: 5.9 +/- 6.3 versus TURP: 8.6 +/- 7.1, P = 0.16), quality-of-life
      score (TUVP: 1.1 +/- 1.2 versus TURP: 1.7 +/- 1.4, P = 0.09), and mean maximal
      urinary flow rate (TUVP: 21 +/- 9 mL/s versus TURP: 17.9 +/- 13.1 mL/s, P =
      0.17), with decreases in the mean postvoid residual volume (TUVP: 27.3 +/- 44.3
      mL versus TURP: 10.7 +/- 13.1 mL, P = 0.08). Two patients in each group (4%)
      developed urethral strictures. Two TURP patients (4%) developed bladder neck
      strictures compared with one TUVP patient (2%). In each arm, 7 patients (13%)
      underwent reoperation during a 5-year period (approximate reoperation rate: 3% in
      each arm per year). Postoperatively and during 3 years of follow-up, impotence
      was reported in 17% of the TUVP group and 11% of the TURP group (P = 0.49);
      retrograde ejaculation was reported in 72% of the TUVP group and 89% of the TURP
      group (P = 0.47). CONCLUSIONS: Our 5-year follow-up results confirm that TUVP is
      as effective as standard TURP in the treatment of moderate-size benign prostatic
      hyperplasia. The reoperation rate and long-term complication rate are comparable
      and the initial improvement has been maintained during a 5-year period for most
      patients in both groups.

PMID- 12809892
TI  - Combination of interstitial laser coagulation and transurethral resection of the
      prostate: ex vivo evaluations.
AB  - OBJECTIVES: To evaluate the combination of interstitial laser coagulation (ILC)
      and transurethral resection of the prostate (TURP) in an ex vivo model.
      Perioperative bleeding is still regarded as the main complication of conventional
      TURP. The minimally invasive procedure ILC and the highly effective TURP seem to
      be a promising concept to improve hemostasis. METHODS: Isolated blood-perfused
      porcine kidneys were used to determine hemostatic efficacy of different
      interstitial laser procedures (neodymium:yttrium-aluminum-garnet [Nd:YAG], 1064
      nm; and holmium:YAG [Ho:YAG], 2100 nm) in combination with conventional TURP.
      Bleeding could thus be quantified in relation to tissue ablation for the
      different techniques. Additionally, the specimens were evaluated histologically.
      RESULTS: A combination of Nd:YAG ILC, followed by TURP, resulted in significantly
      (P <0.001) reduced bleeding compared with TURP alone for a standardized ablation
      volume of 16 cm(3) of perfused kidney tissue (5.1 mL/min versus 24.1 mL/min).
      Similarly, significantly (P <0.001) better hemostasis was demonstrated with the
      combination of Ho:YAG ILC compared with TURP alone (4.8 mL/min versus 24.1
      mL/min). The differences between the two laser procedures were not significant.
      The histologic examinations revealed significantly larger coagulation zones for
      the groups pretreated with Nd:YAG ILC or Ho:YAG ILC compared with TURP alone.
      CONCLUSIONS: ILC before conventional TURP leads, ex vivo, to a significantly
      superior hemostasis compared with TURP alone. The hemostatic effects of Nd:YAG
      and Ho:YAG laser treatments seem comparable.

PMID- 12809893
TI  - Bicycle riding has no important impact on total and free prostate-specific
      antigen serum levels in older men.
AB  - OBJECTIVES: To investigate whether bicycle riding significantly alters total
      prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA)
      serum concentrations in potential candidates for prostate cancer screening.
      METHODS: Thirty-three men, ranging in age from 50 to 74 years (mean 61 +/- 8),
      rode a 13-mile bicycle course. Blood samples for PSA analysis were drawn
      immediately before and 1 hour after cycling for 90 minutes. The precycling and
      postcycling tPSA, fPSA, and %fPSA values were compared using the Wilcoxon matched
      pairs test, with P = 0.01 set as the significance level. RESULTS: Changes between
      precycling and postcycling values for tPSA (P = 0.517), fPSA (P = 0.048), and
      %fPSA (P = 0.166) were not statistically significant. CONCLUSIONS: Physical
      activity combined with perineal pressure as induced by a 13-mile bicycle tour has
      no diagnostic impact on PSA values.

PMID- 12809894
TI  - Prospective evaluation of a 21-sample needle biopsy procedure designed to improve
      the prostate cancer detection rate.
AB  - OBJECTIVES: To evaluate prospectively the diagnostic yield of a 21-sample
      ultrasound-guided needle biopsy procedure for prostate cancer in patients with
      elevated serum prostate-specific antigen and/or abnormal digital rectal
      examination findings. METHODS: Between December 2000 and May 2002, 303 patients
      underwent 21-sample needle biopsy under local anesthesia, comprising sextant
      biopsies at a 45 degrees angle, 3 biopsies in each peripheral zone at an 80
      degrees angle, 3 biopsies in each transition zone (TZ), and 3 biopsies in the
      midline peripheral zone. Morbidity was assessed clinically. A short questionnaire
      was filled out by 90 consecutive patients. RESULTS: The cancer detection rate
      using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral
      biopsies), 18 samples (sextant plus lateral plus TZ biopsies), and 21 samples
      (sextant plus lateral plus TZ, plus midline biopsies) was 22.7%, 28.3%, 30.7%,
      and 31.3%, respectively. The 21-sample procedure statistically improved the
      cancer detection rate by 37.9% relative to the 6-sample procedure. The
      improvement was most marked in patients with a prostate volume of more than 40
      cm(3) (48.3%), patients with Stage T1c prostate disease (44.9%), patients
      undergoing repeat biopsy (66.2%), and patients with prostate-specific antigen
      levels greater than 10 ng/mL (38.5%). Adverse effects were infrequent (3%),
      consisting of prostatitis in 3 patients, acute urinary retention in 6 patients,
      and rectal bleeding requiring hospitalization in 1 patient taking aspirin. Using
      the questionnaire, 84% of patients reported macroscopic hematuria for an average
      of 3.4 days and hematospermia for 12.8 days, and 45% reported minor rectal
      bleeding lasting 1.1 days. The mean pain score, with a visual analog scale
      ranging between 0 (no pain) and 10 (intense pain), was 4.56. CONCLUSIONS: A 21
      sample needle biopsy procedure increased the prostate cancer detection rate
      relative to a 6-sample procedure, without increasing morbidity. Patients with
      elevated prostate-specific antigen values should undergo sextant biopsies and at
      least 6 additional biopsies in the peripheral zone and 6 in the TZ.

PMID- 12809895
TI  - Predicting biochemical recurrence after radical prostatectomy for patients with
      organ-confined disease using p27 expression.
AB  - OBJECTIVES: It is unclear why men who undergo radical prostatectomy (RP) and are
      found to have pathologically organ-confined disease develop prostate-specific
      antigen (PSA) recurrences. We previously found that patients with less than 45%
      of cells in the prostate needle biopsy specimen (PNBx) staining positive for the
      cell cycle regulator p27 had a significantly increased risk of biochemical
      recurrence after RP. We sought to determine whether p27 staining in the PNBx
      specimen might serve as a molecular marker for PSA failure in the subset of
      patients who develop PSA recurrence despite organ-confined disease at RP.
      METHODS: The PNBx specimens of 161 men treated with RP between 1991 and 2000 were
      examined for p27 expression using immunohistochemistry. The p27 cutpoint of less
      than 45% expression was used to define the high and low-risk categories. Patients
      were separated into two groups for analysis: organ-confined (pT2 and negative
      surgical margins) and non-organ-confined (pT2 with positive surgical margins,
      pT3, pT4, or lymph node involvement). The mean and median follow-up for patients
      with organ-confined and non-organ-confined disease was 47 and 43 months and 42
      and 38 months, respectively. Multivariate Cox proportional hazards analysis was
      used to examine the preoperative clinical variables that were the strongest
      predictors of biochemical recurrence after RP among each group. RESULTS: Among
      organ-confined patients, p27 expression was the only significant independent
      predictor of the time to biochemical recurrence after RP (hazard ratio 5.15, 95%
      confidence interval 1.41 to 18.83, P = 0.013). Among patients with non-organ
      confined disease, the percentage of biopsy tissue with cancer, biopsy Gleason
      score, and PSA level were independent predictors of PSA recurrence. p27
      expression was not a significant independent predictor of PSA recurrence among
      men with non-organ-confined disease. CONCLUSIONS: p27 expression in the PNBx was
      a significant independent predictor of PSA failure for patients with
      pathologically organ-confined disease, but not for those with non-organ-confined
      disease. Patients with organ-confined disease but low p27 expression had a
      greater than fivefold risk of developing PSA recurrence than were men with high
      p27 expression, suggesting that p27 may be a molecular marker associated with
      micrometastatic disease at the time of RP.

PMID- 12809896
TI  - Familial prostate cancer cases before and after radical prostatectomy do not show
      any aggressiveness compared with sporadic cases.
AB  - OBJECTIVES: To compare the clinical and biologic features at diagnosis between
      sporadic and familial clinically localized prostate cancer (CaP), and to compare
      the prognosis of familial with that of sporadic cases after radical prostatectomy
      in southwestern Europe. METHODS: Eighty-five sporadic (one case of CaP) and 37
      familial (two or more CaP cases in the family) patients with clinically localized
      CaP undergoing radical prostatectomy were compared regarding preoperative (mean
      age, clinical status, mean prostate-specific antigen level, and mean Gleason
      score at diagnosis) and postoperative (pT, pN, and pathologic Gleason score)
      parameters using the Student t test, Fisher's exact test, and the chi-square
      test. The biochemical relapse-free survival for each group was compared using the
      Kaplan-Meier method and the log-rank test. RESULTS: The mean follow-up was about
      51.8 months (range 1 to 156) in the sporadic group and 35 months (range 1 to 96)
      in the familial group. No specific preoperative and postoperative clinical or
      biologic feature was associated with familial CaP. Biochemical relapse occurred
      in 40.5% (15 of 37) of cases when the proband had a positive family history of
      CaP versus 32.9% (28 of 85) in the sporadic cases (P = 0.42). Biochemical relapse
      free survival curves did not display any difference (P = 0.46) between familial
      and sporadic CaP. CONCLUSIONS: In this population, the outcome after radical
      prostatectomy is similar in those with and without a family history. Thus, the
      natural history of CaP seems to follow the same path whether the triggering point
      is inherited or acquired for this subset of patients during this period.

PMID- 12809897
TI  - Meeting the information needs of Australian men with prostate cancer by way of
      the internet.
AB  - OBJECTIVES: To assess the information preferred by Australian men for a prostate
      cancer website, to establish such a website, and to assess whether the first 2
      years of use of the website reflected those needs. Successful patient information
      programs must be relevant to the target group's needs. METHODS: In phase 1, we
      surveyed Australian prostate cancer support group members asking for the
      preferred functions and content of an Australian website. In phase 2, a website
      was developed (http://www.prostatehealth.org.au) with the requested content
      derived from a urology service, state Cancer Councils, and medical directory and
      support group organizations. In phase 3, usage patterns of the site were analyzed
      using Web-Trends software for the first 2 years (2000 to 2002). RESULTS: The
      phase 1 survey of 54 men (response rate 69.2%) showed the most preferred pages
      were understanding diagnosis/understanding treatment (59%), on-line help-line
      (49%), and news sections (44%) with listings of Australian support groups (22%).
      Credible, up-to-date Australian-oriented content was requested. In phase 2, the
      site developed had five searchable databases with requested medical content from
      a urology service, support group and treatment center listings, and an on-line
      help-line run by a cancer council. In phase 3, after 2 years of operation, the
      site averaged 150,000 hits and 15,000 page views per month, with 46% of visitors
      from Australian domains. Most visited sections closely followed the needs
      assessment. CONCLUSIONS: Needs assessment is an important precursor to targeted
      web-based education programs. Nonmedical, community-based information is
      important to men with prostate cancer, as is information on diagnosis and
      treatment.

PMID- 12809898
TI  - Salvage radiotherapy for biochemical failure of radical prostatectomy: a single
      institution experience.
AB  - OBJECTIVES: To review the efficacy of salvage radiotherapy (RT), to treat
      elevated prostate-specific antigen (PSA) levels for presumed local recurrence of
      prostatic adenocarcinoma after retropubic prostatectomy, and identify the factors
      that may predict for successful treatment. METHODS: Fifty-one patients with
      hormonally naive pT2-3N0-1M0 prostate cancer were treated with RT for locally
      persistent or recurrent disease. The patients received a median dose of 65.7 Gy
      (range 61.2 to 72.3) to the prostate bed. Successfully treated patients had
      undetectable PSA levels; the endpoint of the study was biochemical failure.
      RESULTS: The median follow-up was 3.8 years; 42 of 51 patients had at least 2
      years of follow-up. Twenty-three patients (45%) were biochemically free of
      disease. The estimated biochemically free of disease rate at 3 and 5 years was
      56% and 16%, respectively. Whether the patients were treated for persistently
      elevated PSA levels or for rising PSA levels from undetectable levels after
      retropubic prostatectomy, their PSA values were equally likely to drop to
      undetectable levels (65%). Univariate analysis demonstrated two factors that
      significantly predicted for successful salvage treatment: the absence of seminal
      vesicle invasion and the absence of lymphovascular invasion. A pretreatment PSA
      level less than 0.425 ng/mL trended toward statistical significance (P = 0.059).
      Only seminal vesicle invasion maintained significance on multivariate analysis.
      The RT was well tolerated, and the gastrointestinal and genitourinary toxicity
      was largely Radiation Therapy Oncology Group grade 1. CONCLUSIONS: Salvage RT is
      moderately effective in treating patients with locally persistent or recurrent
      prostate adenocarcinoma. Seminal vesicle invasion and lymphovascular invasion
      predicted for unsuccessful treatment.

PMID- 12809899
TI  - The combination of estramustine and mitoxantrone in hormone-refractory prostate
      cancer: a phase II feasibility study conducted by the Hellenic Cooperative
      Oncology Group.
AB  - OBJECTIVES: To consider the safety profile and therapeutic value of the
      combination of estramustine and mitoxantrone in a bimonthly schedule to treat
      hormone-refractory prostate cancer. The survival of patients with prostate cancer
      who relapse after androgen ablation is limited and the therapeutic options are
      restricted. METHODS: Twenty-nine patients with relapse after previous treatment
      were included in the study; however, 3 patients who refused to start treatment
      were not included in the analysis, leaving 26 eligible patients. The median age
      was 64 years (range 44 to 82), the World Health Organization performance status
      ranged from 1 to 3, and the mean prostate-specific antigen level was 103 ng/mL
      (range 1 to 620). The Gleason score ranged from 2 to 9. The patients received a
      total of 208 therapeutic cycles (mean 8, range 3 to 24). Every cycle consisted of
      oral estramustine 140 mg, 3 times a day continuously, and intravenous
      mitoxantrone 20 mg (total dose). The regimen was repeated every 2 weeks. RESULTS:
      Twenty-seven percent of patients with measurable soft-tissue disease demonstrated
      an objective response, which included one complete and six partial responses.
      Thirteen patients (50%) had a greater than 50% reduction in serum prostate
      specific antigen level. The median duration of response was 9.2 months, and the
      median survival for all patients was 15 months. The most common side effects were
      neutropenia and thrombocytopenia. CONCLUSIONS: The combination of estramustine
      and mitoxantrone is safe, well tolerated, and relatively active in patients with
      hormone-refractory prostate cancer. More patients are needed to partake in Phase
      III studies to establish the survival benefit that this combination may offer.

PMID- 12809900
TI  - Penile verrucous carcinoma successfully treated by intra-aortic infusion with
      methotrexate.
AB  - OBJECTIVES: Penile verrucous carcinoma is characterized by aggressive local
      growth and a low metastatic potential. Lower abdominal aortic infusion
      chemotherapy has the main advantage of delivering a very high concentration of an
      anticancer drug to the whole pelvic area, including the penis, and is especially
      suitable to treat penile verrucous carcinoma. METHODS: From 1991 to 2000, 4 cases
      of penile verrucous carcinoma were treated by continuous intra-aortic infusion
      with methotrexate (50 mg) every 24 hours, for an average of 10 days. Citrovorum
      factor (6 mg) was given intramuscularly every 6 hours during the period of
      methotrexate infusion. RESULTS: After treatment, 3 patients achieved complete
      remission. They were living disease free 10 years, 10 months, 6 years, 9 months,
      and 1 year, 8 months after therapy. CONCLUSIONS: Intra-aortic infusion
      chemotherapy is a simple and effective method for penile verrucous carcinoma with
      the unique advantage of preserving cosmetic and functional integrity. It may be
      considered an effective alternative treatment for penile verrucous carcinoma. By
      using this simple method many unnecessary penectomies can be avoided.

PMID- 12809901
TI  - Outcomes of vasectomy reversal performed for men with the same female partners.
AB  - OBJECTIVES: To review the fertility outcomes of patients who underwent vasectomy
      reversal and attempted conception with the same female partners. METHODS: A
      retrospective review of two surgeons' experience was performed. Patency was
      defined as the presence of motile sperm. Patients with less than 6 months of
      follow-up were excluded from the patency rate analysis unless they had sperm in
      the semen sample. Similarly, patients with less than 6 months of follow-up or no
      ongoing interest in establishing conception were excluded from the pregnancy rate
      analysis unless they had established a pregnancy. RESULTS: Of 200 consecutive
      men, 34 (17%) underwent microsurgical vasectomy reversal with the same female
      partner. All but two of the couples had previous proven fertility. The procedures
      performed for those who pursued fertility were bilateral vasovasostomy (n = 27),
      vasovasostomy/vasoepididymostomy (n = 4), and bilateral vasoepididymostomy (n =
      1). The mean obstructive interval was 5 years (range 4 months to 10 years). The
      mean female partner age was 31.9 years (range 26 to 38). The median follow-up was
      8 months (range 1 to 48). Patency was achieved in 27 (93%) of 29, and pregnancy
      occurred in 15 (60%) of 25 cases with sufficient follow-up. The ongoing or
      delivered rate was 56% (14 of 25). Female factor problems were present in three
      couples, and two miscarriages occurred for couples with known female factor
      problems. CONCLUSIONS: Microsurgical vasectomy reversal may have higher success
      rates when performed for couples with the same female partner. These results may
      be related to a shorter obstructive interval and a history of previous fertility
      as a couple.

PMID- 12809902
TI  - Unilateral urinary flow impairment at the pelviureteral junction: outcome of
      renal function with respect to therapeutic strategy.
AB  - OBJECTIVES: To evaluate the renal function outcome in children with unilateral
      hydronephrosis and urinary flow impairment at the pelviureteral junction with
      respect to the therapeutic strategy. METHODS: We retrospectively selected 45
      children with iodine-123-hippuran renography performed at diagnosis and after 3
      or more years of follow-up. All children had bilateral nonobstructive pattern
      findings on diuretic renography at follow-up. Eleven children were treated
      conservatively, and 34 underwent unilateral pyeloplasty. Split and individual
      renal function, measured by an accumulation index, was computed from background
      corrected renograms for the affected and contralateral kidneys at diagnosis and
      the follow-up examination. RESULTS: Of 11 children treated conservatively, 9 had
      normal bilateral function at diagnosis, all had reached normal function at follow
      up. Of the 34 operated kidneys, 12 (38%) had initially normal function that
      remained normal at the follow-up examination, and 22 had impaired function that
      had normalized at the follow-up examination in 15 (68%). The function of the
      contralateral kidneys was increased in 5 of 8 children with persistently abnormal
      affected kidneys. Pyeloplasty was performed in 23 children (68%) and 11 children
      (32%) younger and older than 1 year, respectively. The function of the affected
      kidneys increased in both groups, but normalization occurred only in the younger
      children. CONCLUSIONS: Of the children selected for conservative treatment, 82%
      had normal bilateral renal function at diagnosis that was normal in all at the
      follow-up examination. Of the children treated surgically, 65% had initially
      impaired function of the affected kidney that improved in 87% after pyeloplasty.
      Normalization of function was observed only in children who were younger than 1
      year old at surgery. Persistently low function of the affected kidney was
      compensated for by the contralateral one regardless of the age at surgery.

PMID- 12809905
TI  - Tubeless Barcat: a patient-friendly hypospadias procedure.
AB  - OBJECTIVES: To determine whether the distinct advantages of a catheter-free
      hypospadias repair can be obtained with a Barcat procedure without an adverse
      effect on surgical outcome. METHODS: A retrospective review was performed on
      consecutive patients who had undergone a catheter-free Barcat repair from July
      1998 to May 2002. Patient records were examined for information regarding age,
      meatal location, primary or secondary procedure, operative time, postoperative
      follow-up, and complications. RESULTS: Thirty-six consecutive catheter-free
      Barcat hypospadias repairs were performed in the review period. Patient age
      ranged from 6 months to 9 years (mean 26 months). All patients either had a
      coronal meatus or a subcoronal meatus. Thirty-three patients (92%) underwent a
      primary repair. Three patients (8%) underwent the repair as a secondary procedure
      after a previous failed procedure. The mean follow-up was 25 months. One patient
      required a single catheterization in the immediate postoperative period for
      urinary retention. Another patient had glans separation and meatal retrusion
      requiring a revision procedure. All the other patients achieved a satisfactory
      cosmetic result with an orthotopic slit-like meatus. CONCLUSIONS: The Barcat
      hypospadias repair may be performed in patients with distal hypospadias without
      the use of a postoperative urethral catheter. Foregoing a catheter had no adverse
      effect on the surgical outcome with reduced patient discomfort.

PMID- 12809907
TI  - Role of laparoscopy in patients with previous negative exploration for impalpable
      testis.
AB  - OBJECTIVES: To evaluate the impact of laparoscopy in the treatment of patients
      with previous negative inguinal exploration for impalpable undescended testes.
      METHODS: A retrospective review was performed of patients who underwent
      laparoscopy after prior incomplete or "questionable" negative inguinal
      explorations for nonpalpable undescended testes. RESULTS: Twenty-seven males aged
      1 to 22 years old, with 30 impalpable testes, underwent laparoscopy after prior
      negative open exploration. The operative notes were available for all patients.
      In 9 patients (33%), blind-ending spermatic vessels, vas deferens, and a closed
      ring were found. However, in the remaining 18 patients (67%), viable intra
      abdominal or inguinal gonads (9 patients) and intra-abdominal remnants (9
      patients) were identified. In 1 patient, seminoma of an intra-abdominal testis
      was present. CONCLUSIONS: When a patient is referred with an inconclusive
      previous open exploration for an impalpable gonad, laparoscopy has an important
      role in establishing or refuting the diagnosis of an absent testis. Moreover,
      therapeutic laparoscopy provides definitive options to standard open techniques
      when a viable testis or remnant is encountered. In this study, laparoscopy proved
      more accurate than open exploration with operative notes available defining the
      nature of the exploration.

PMID- 12809909
TI  - Risk of renal scarring in vesicoureteral reflux detected either antenatally or
      during the neonatal period.
AB  - OBJECTIVES: To evaluate both the demographic features and the renal outcome of
      fetal vesicoureteral reflux (VUR), two well-defined populations were analyzed:
      those with hydronephrosis detected by obstetric ultrasonography, and neonates
      diagnosed after developing their first urinary tract infection within the first 4
      postnatal weeks. METHODS: Twenty-one neonates with antenatally detected VUR were
      compared with 30 patients with neonatally detected symptomatic disease. The mode
      of presentation, fate of reflux, and renal outcome were analyzed. RESULTS:
      Significantly more bilateral dilating VUR was found in postnatally versus
      antenatally diagnosed patients (53% versus 29%; P = 0.05). Fourteen percent
      presented with congenital renal dysplasia. No difference was found in the
      incidence of congenital dysplasia between the two groups. Focal renal scars
      developed during follow-up in 19% of renal units. New scars were observed in
      dilating VUR only, especially in grades 4 and 5 (P <0.05), and these were
      exclusively in the postnatal patient group (P <0.005). CONCLUSIONS: Several
      demographic features of fetal VUR differ, depending on whether detected
      antenatally or postnatally. The incidence of bilateral dilating VUR was greater
      in postnatally detected cases, suggesting a more severe manifestation of the
      disease. Renal injury occurred in an appreciable number of renal units. The
      damage may be of congenital origin or may be acquired secondary to urinary tract
      infection. The risk of acquired renal scarring is particularly significant if
      dilating VUR is not detected until neonatally after the first urinary tract
      infection.

PMID- 12809911
TI  - Ureteroscopically assisted percutaneous renal access.
AB  - Percutaneous nephrostolithotomy is a common procedure for removing kidney stones.
      Obtaining percutaneous access can be difficult in some patients. We describe our
      technique of ureteroscopically assisted percutaneous renal access for patients in
      whom standard percutaneous access may be challenging.

PMID- 12809912
TI  - Laparoscopic radical nephrectomy incorporating intraoperative ultrasonography for
      renal cell carcinoma with renal vein tumor thrombus.
AB  - The purpose of this study was to describe the technique of laparoscopic right
      radical nephrectomy incorporating intraoperative, real-time ultrasonography in
      the management of renal cell carcinoma with level 1 renal vein tumor thrombus.
      With the patient in a modified flank position, a transperitoneal four-port
      approach was used to laparoscopically resect an 8.5-cm right renal mass with
      tumor thrombus extending to, but not into, the inferior vena cava. Early arterial
      control with gentle traction on the right renal vein provided a short proximal
      renal venous segment devoid of tumor on laparoscopic inspection. Intraoperative
      laparoscopic ultrasonography allowed confident identification of the proximal
      extent of the tumor thrombus. After hilar control, complete resection and intact
      removal of the renal specimen was performed using standard non-hand-assisted
      laparoscopic techniques. The actual surgical time was 180 minutes. Surgical
      resection was successfully performed laparoscopically. No postoperative
      complications or hospital readmission occurred. Pathologic examination confirmed
      T3b renal cell carcinoma with negative surgical margins. Laparoscopic right
      radical nephrectomy incorporating intraoperative, real-time ultrasonography is
      feasible in the management of renal cell carcinoma with a large-sized level 1
      renal vein thrombus. Additional studies are necessary to evaluate its role in
      urologic oncologic surgery.

PMID- 12809913
TI  - Rectus abdominis vaginoplasty after anterior exenteration for urologic
      malignancy.
AB  - INTRODUCTION: Vaginal resection is occasionally required in female patients who
      undergo anterior exenteration for invasive lower urinary tract malignancy. We
      have used a rectus abdominis myocutaneous flap to reconstruct the vagina and
      perineum after extensive local resection of bladder and urethral carcinoma.
      TECHNICAL CONSIDERATIONS: Either a left or right rectus flap is used. Once
      anterior exenteration, partial vaginectomy, and urinary diversion are completed,
      the median infraumbilical incision is extended superiorly to form an elliptical
      skin paddle centered over the superior half of the muscle. The superior
      epigastric vessels are ligated, the cephalad end of the muscle is divided at the
      level of the costal margin, and the flap is progressively elevated out of the
      rectus sheath by sequentially dividing the lateral perforating nerves and
      vessels. As the muscle is elevated, the inferior epigastric pedicle is carefully
      preserved and followed inferiorly to its origin from the external iliac artery.
      Once a length of muscle sufficient for it to reach the perineum is mobilized, the
      flap is carried transpelvically. For complete vaginal reconstruction, the flap
      may be inverted into a tube, with the cephalic portion anchored to the perineum.
      Alternatively, the skin paddle may be used to fill tissue defects in the vagina
      and pelvic floor. The anterior abdominal wall fascia and skin edges at the donor
      site are closed primarily. We have successfully applied this technique in 4
      patients who underwent anterior exenteration for invasive bladder and urethral
      carcinoma. CONCLUSIONS: Rectus abdominis vaginoplasty is a viable surgical option
      for reconstruction after anterior exenteration with vaginal resection for
      invasive cancer of the bladder and urethra.

PMID- 12809915
TI  - A new technique in scrotal reconstruction: short gracilis flap.
AB  - INTRODUCTION: The gracilis flap is commonly used for the reconstruction of the
      genitalia and scrotum, but the procedure has problems owing to a pedicle away
      from the pubic tubercle and a bulky nature. A new use of this flap without
      including its pedicle has been described as the "short gracilis flap" and has
      been used for vulvovaginal, perineal, and inguinal reconstruction with
      considerable results. However, scrotal use has not yet been mentioned. TECHNICAL
      CONSIDERATIONS: We applied the flap in 2 cases of Fournier's gangrene for scrotal
      reconstruction. The flap dissection was straightforward. Because one uses the
      vascularity through the origin of the muscle on the pubic bone, the short
      gracilis flap has the advantage of greater mobility. No "dog ears" or bulky zones
      because of pedicle protection are created. The skin island is transposed more
      proximally than with the conventional gracilis flap where the circumference of
      the thigh is greater, thus allowing primary closure easily. The flap does not
      have any vascular problems. The donor site scars can be hidden more easily, and
      the flap atrophies significantly with time. CONCLUSIONS: The short gracilis flap
      may be a good choice for selected cases of scrotal reconstruction.

PMID- 12809916
TI  - Sclerosing peritonitis.

PMID- 12809917
TI  - Fetal bladder rupture due to anteriorurethral valves.
AB  - A rupture of the fetal bladder that resulted in urinary ascites has rarely been
      reported in published studies. We present the first case of a spontaneous rupture
      of the fetal bladder, due to an anterior urethral valve, in which the diagnosis
      was suspected prenatally by means of Doppler ultrasonography and was confirmed
      postnatally.

PMID- 12809918
TI  - Reninoma treated with nephron-sparing surgery.
AB  - A 14-year-old hypertensive boy was evaluated in our clinic. The physical
      examination was essentially normal except for his high blood pressure. Laboratory
      findings showed increased plasma renin activity. Abdominal ultrasonography
      detected a hypoechoic, 2-cm mass in right kidney. Contrast-enhanced computed
      tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing
      cortical lesion in the middle of the right kidney. Magnetic resonance angiography
      documented bilateral normal renal arteries. With a preoperative diagnosis of
      reninoma, the patient underwent nephron-sparing surgery. Intraoperative frozen
      section analysis revealed a benign lesion. Subsequently, histopathologic
      examination and electron microscopy confirmed the diagnosis of juxtaglomerular
      cell tumor. The patient remained normotensive in the postoperative period. Follow
      up intravenous urography showed bilateral normally functioning kidneys.

PMID- 12809919
TI  - "Indeterminate" cystic lesion of the kidney partially lined by small cells with
      clear cytoplasm--malignant or benign?
AB  - Complex renal cysts, which present radiographically as "indeterminate for
      malignancy" (Bosniak category III), can prove challenging both pathologically and
      clinically. We report a case of a renal cyst that, by standard radiographic and
      histologic criteria, should have been diagnosed as a malignant cystic renal cell
      carcinoma. However, the cytogenetic profile appeared more closely consistent with
      cystic renal adenoma or low-grade papillary renal cell carcinoma--tumors with
      limited metastatic potential. We postulate that other, similarly complex, renal
      cysts might also be more precisely defined by meticulous histopathologic
      examination, supported by cytogenetic study.

PMID- 12809920
TI  - Urinary retention in a patient with West Nile virus.
AB  - West Nile Virus (WNV) has received much recent attention due to multiple
      outbreaks in North America, its insidious onset in many patients, and a wide
      variety of neurologic manifestations. A 45-year-old man who exhibited urinary
      retention as a presenting symptom of WNV infection is presented herein. We
      believe this to be the first reported case of a urologic sequela secondary to WNV
      infection.

PMID- 12809921
TI  - False fracture of the penis.
AB  - Penile fracture is an uncommon, but well-described, entity that requires emergent
      treatment. The classic, "text-book" history, a blow to the erect penis
      accompanied by a "snap," pain, and immediate detumescence, is not universally
      present. We report 2 cases of "false" penile fracture, a condition that closely
      mimics "true" penile fracture. Perhaps the most distinguishing symptoms are the
      absence of the "snap" and gradual detumescence, both of which suggest false
      fracture but are not specific. It is our intention to bring this condition to the
      attention of general urologists who may see it in clinical practice and to guide
      them in its management.

PMID- 12809922
TI  - Tricorporal priapism in a patient with metastatic esophageal cancer.
AB  - Tricorporal priapism refers to priapism involving the corpora cavernosa and
      spongiosum. It is exceedingly rare and, depending on the etiology, may be
      difficult or impossible to treat. We present a case of tricorporal priapism in a
      patient with metastatic esophageal cancer and complete thrombosis of all venous
      vasculature below the level of the renal veins. Ultimate management consisted of
      comfort measures and minimizing the risk of infection. In this case of
      tricorporal ischemic priapism, the recognized treatment options for ischemic
      priapism were not applicable, because no viable shunt targets were available. The
      treating urologist should be aware of this potential clinical entity and be
      prepared to offer conservative management.

PMID- 12809923
TI  - Adrenal hemorrhage mimicking an abdominal aortic aneurysm.
AB  - The adrenal gland is the most common site of extranodal spread from primary lung
      cancer. We report a case of adrenal hemorrhage secondary to metastasis in a
      patient with primary large cell carcinoma of the lung presenting as a suspected
      ruptured abdominal aortic aneurysm.

PMID- 12809924
TI  - Use of sarcoma-based chemotherapy in a case of congenital mesoblastic nephroma
      with liver metastases.
AB  - Congenital mesoblastic nephroma was originally considered to be a benign
      neoplasm. A more aggressive cellular form, however, that has a close relationship
      to congenital fibrosarcoma, is widely described. Previous reported sites of
      metastases are the lungs, heart, brain, and bone. We describe a patient with
      isolated metastasis to liver and review the management, together with evidence
      that it may be more appropriate to use a vincristine, ifosfamide, doxorubicin,
      and etoposide (VIDE) regimen rather than Wilm's tumor-based regimens in those
      cases for which chemotherapy is indicated.

PMID- 12809925
TI  - Male genital malformations associated with right renal agenesis.
AB  - A 30-year-old man visited our department complaining of discomfort on
      micturition. Hypoplasia of the bilateral epididymis, impalpable vas deferens, and
      prostatic tenderness were noted. Diagnostic imaging revealed agenesis of the
      right kidney, cystic dilation of the right seminal vesicle, and a prostatic
      utricle cyst. Examination of the genital tract confirmed aplasia of the left
      seminal vesicle and vas deferens and hypoplasia of the right seminal vesicle. On
      the basis of postoperative extravasation of contrast medium to the right
      epididymis, cystic dilation of the right seminal vesicle was diagnosed.

PMID- 12809926
TI  - Identification and preliminary clinical evaluation of a 50.8-kDa serum marker for
      prostate cancer.
AB  - OBJECTIVES: To identify a 50.8-kDa biomarker to perform a preliminary clinical
      evaluation of its utility as an aid in the early detection of prostate cancer.
      METHODS: The 50.8-kDa protein, previously called NMP48, was partially purified
      from the serum of an individual with prostate cancer and identified by peptide
      mass fingerprinting of tryptic peptides from an in-gel digest. Serum samples were
      obtained from men with biopsy-confirmed prostate cancer, high-grade prostatic
      intraepithelial neoplasia, and benign histologic features, from men with
      clinically defined benign prostatic hyperplasia, and from controls without
      prostatic disease. These samples were analyzed for the presence of the biomarker
      by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.
      RESULTS: The 50.8-kDa protein was identified by peptide mass fingerprinting as
      being related to vitamin D-binding protein. It was found in 96% of the sera from
      individuals with prostate cancer (n = 52) including 11 of 12 specimens that
      exhibited prostate-specific antigen values of less than 4 ng/mL. The 50.8-kDa
      protein was found in 10 of 19 samples from men with prostatic intraepithelial
      neoplasia; however, it was not detected in the sera of 5 (75%) of 20 individuals
      with benign prostatic histologic features, 7 (70%) of 10 with clinical benign
      prostatic hyperplasia, 8 (80%) of 10 patients who had previously undergone
      radical prostatectomy, or 48 (96%) of 50 specimens from healthy controls.
      CONCLUSIONS: Although the study cohort was relatively small, the data suggest
      that an assay for the 50.8-kDa protein may be useful for the early detection of
      prostate cancer. Additional elucidation of its structure may yield insight into
      the development of this disease.

PMID- 12809927
TI  - DNA cytometric features in biopsies of TaT1 urothelial cell cancer predict
      recurrence and stage progression more accurately than stage, grade, or treatment
      modality.
AB  - OBJECTIVES: To compare retrospectively the predictive value for recurrence and
      stage progression of DNA ploidy and S-phase fraction by flow cytometry and highly
      automated ultrafast image cytometry (ICM) in biopsies of TaT1 urothelial cell
      carcinomas (UCCs) of the urinary bladder with stage, grade, other pathologic
      features, and treatment. METHODS: Three experienced pathologists reviewed the
      stage and grade of 228 UCCs; 193 (85%) consensus cases were analyzed further. We
      had enough material for single-cell suspensions for both flow cytometry and ICM
      in 183 cases (94.8%). The 2001 European Society for Analytical Cellular Pathology
      standards for DNA ICM were followed. The predictive value of DNA features,
      classic prognosticators (stage, grade, carcinoma in situ, multicentricity), and
      treatment modality for recurrence and stage progression were analyzed with
      univariate (Kaplan-Meier) survival and multivariate (Cox model) regression
      analysis. Ta and T1 cases were analyzed separately. RESULTS: Of the 228 cases, 88
      (51.5%) recurred and 13 (7.6%) progressed. On univariate analysis, most of the
      DNA features studied were statistically significant. Treatment modality and grade
      were only prognostic for progression (not for recurrence) and only in Ta cases.
      On multivariate analysis, DNA ICM features performed best; the strongest
      recurrence predictor for Ta UCC was a DNA index (DI) of 1.0 versus all others,
      and for T1 UCC, a DI of less than 1.3 versus 1.3 or greater. The best stage
      progression predictor for Ta UCCs was a DI of 1.0 plus an S-phase fraction of
      less than 10%, and for T1 UCCs, a DI of less than 1.3 versus 1.3 or greater. With
      multivariate analysis, sex, age, grade, carcinoma in situ, multicentricity, and
      treatment modality were excluded once the DNA ICM features were selected.
      CONCLUSIONS: DNA image cytometric features predict recurrence and stage
      progression in TaT1 UCC biopsies more accurately than classic prognostic factors,
      independent of treatment modality.

PMID- 12809928
TI  - Effectiveness of vaginally administered oxybutynin on rabbit bladder function.
AB  - OBJECTIVES: To demonstrate the effectiveness of vaginally delivered oxybutynin on
      bladder function. Oxybutynin has been used for treatment of urge urinary
      incontinence for more than 20 years. METHODS: Thirty female New Zealand White
      rabbits were used for this experiment. Each rabbit was anesthetized, and the
      carotid artery was cannulated for blood pressure monitoring. The bladder dome was
      catheterized for both monitoring of bladder pressure and cystometry. After
      initial cystometry, acetylcholine (ACh) was injected into the vesical artery at
      15-minute intervals for 4 hours. Cystometry was performed at the 2-hour mark and
      at the end of each experiment (4 hours). After the third ACh administration,
      vaginal or oral oxybutynin was given and the effect on the response to ACh, blood
      pressure, and cystometry was observed. RESULTS: The high dose of oxybutynin
      completely inhibited the response to ACh and significantly inhibited the
      micturition reflex. A 45% inhibition of micturition pressure occurred at the
      intermediate dose. Little effect on compliance after the low dose and a
      significant increase in compliance after the mid-dose occurred. Both the low and
      intermediate doses of oxybutynin reduced the response to ACh to approximately 50%
      of control. No blood pressure effects of vaginal oxybutynin were noted for any
      concentration. Oral oxybutynin showed very similar effects to that of the
      intermediate vaginal dose. CONCLUSIONS: Vaginally delivered oxybutynin was
      effective in decreasing bladder compliance and inhibiting intra-arterial ACh
      stimulated bladder contractions with little or no effect on the vascular effect
      of ACh.

PMID- 12809929
TI  - Decreased in vitro proliferation of bladder epithelial cells from patients with
      interstitial cystitis.
AB  - OBJECTIVES: To determine whether explanted bladder epithelial cells from patients
      with interstitial cystitis (IC) display intrinsically decreased rates of
      proliferation in vitro, and to compare the growth rates of untreated IC and
      normal bladder cells with the rates of normal cells treated with a purified
      antiproliferative factor (APF) at levels found in urine from patients with IC.
      METHODS: Epithelial cell explants were prepared from the bladder biopsies of 4
      patients with IC and 2 asymptomatic controls. Cell proliferation was determined
      by serial counting of trypan blue-negative cells. APF and mock APF were purified
      chromatographically, and activity was determined by (3)H-thymidine incorporation
      into primary normal bladder epithelial cells. Heparin-binding epidermal growth
      factor-like growth factor and epidermal growth factor were measured by enzyme
      linked immunosorbent assay. RESULTS: Bladder epithelial cells from patients with
      IC proliferated significantly less than did control cells by day 2 after serum
      starvation (P = 0.02). Similar inhibition of the proliferation rate was seen in
      control cells treated with APF; APF-induced changes in heparin-binding epidermal
      growth factor-like growth factor, but not epidermal growth factor, production by
      cells were associated with changes in growth rates. CONCLUSIONS: The
      proliferation rate of explanted bladder epithelial cells from patients with IC in
      serum-free medium was significantly less than that of control cells, indicating
      an intrinsic abnormality in IC cell proliferation. This abnormality may be caused
      by APF, which induces reversible inhibition of heparin-binding epidermal growth
      factor-like growth factor production and normal bladder epithelial cell
      proliferation.

PMID- 12809930
TI  - Muscle-derived stem cells seeded into acellular scaffolds develop calcium
      dependent contractile activity that is modulated by nicotinic receptors.
AB  - OBJECTIVES: To explore the contractile activity and physiologic properties of
      muscle-derived stem cells (MDSCs) incorporated into small intestinal submucosa
      (SIS) scaffolds. METHODS: MDSCs were harvested from mice hind leg muscles using
      the preplate technique and stably transfected with a plasmid to express the LacZ
      reporter gene. Fifty different preparations of SIS cultured with MDSCs (MDSC/SIS)
      or SIS alone were incubated at 37 degrees C for 1, 4, and 8 weeks and also were
      mounted in a bath to measure the isometric contractions. RESULTS: LacZ and Masson
      trichrome staining revealed MDSCs could migrate into and distribute throughout
      the SIS and form myotubes. In MDSC/SIS, spontaneous contractile activities were
      noted in the 4-week (five of six specimens) and 8-week (eight of eight specimens)
      cultures, but not in 1-week cultures (n = 11). All SIS control groups after 1 (n
      = 11), 4 (n = 6), and 8 (n = 8) weeks of incubation did not show any activity. In
      most of the 4-week, and all of the 8-week, MDSC/SIS cultures, the frequency and
      amplitude of spontaneous contractile activities were decreased by succinylcholine
      10 microM and 20 microM. Electrical field stimulation, carbachol, and KCl did not
      alter the frequency, amplitude, or pattern of spontaneous contractile activities
      in MDSC/SIS. Spontaneous contractile activities were blocked by Ca(32+)-free
      Krebs solution with ethyleneglycoltetraacetic acid 200 microM and distilled
      water. CONCLUSIONS: MDSCs could be incorporated into SIS-forming myotubes capable
      of contracting. The contractile activity of this three-dimensional construct is
      Ca(2+) dependent and is modulated by nicotinic receptors. MDSC seeding of an
      acellular matrix may become a functional sling to reengineer the deficient
      sphincter or as contractile bladder augmentation.

PMID- 12809932
TI  - Notice of retraction. Different docetaxel-induced apoptotic pathways are present
      in prostate cancer cell lines LNCaP and PC-3.

PMID- 12809931
TI  - PC-SPES.

PMID- 12809933
TI  - Immunoreactivity to pyruvate dehydrogenase complex-E2 in well-defined patients
      with autoimmune hepatitis: Western blot analysis.
AB  - Anti-mitochondrial antibodies (AMA) are frequently detected in sera from patients
      with primary biliary cirrhosis (PBC). Major autoantigens for AMA have been
      identified as members of the 2-oxoacid dehydrogenase enzyme complex family, with
      pyruvate dehydrogenase complex (PDC)-E2 showing strongest reactivity to AMA in
      PBC patients. Recently, anti-PDC-E2 has been found in patients with other
      diseases. Since frequency and significance of anti-PDC-E2 in patients with
      autoimmune hepatitis (AIH) remain obscure, we measured anti-PDC-E2 in sera from
      well-defined AIH cases by Western blotting using bovine heart mitochondrial
      protein and recombinant PDC-E2 protein as antigen sources. All 55 enrolled
      patients fulfilled the international diagnostic criteria for definite or probable
      AIH. Anti-PDC-E2 positivity showed concordance between native and recombinant
      antigens. Anti-PDC-E2 was detected in nine of 55 sera from AIH patients (16%).
      Variables including alkaline phosphatase (ALP) and IgM concentrations, effects of
      prednisolone, and pathologic findings concerning bile ducts showed no significant
      differences between anti-PDC-E2-positive and anti-PDC-E2-negative AIH patients.
      These data indicate that detection of anti-PDC-E2 is not rare in defined AIH, but
      anti-PDC-E2-positive AIH does not represent an intermediate entity in a clinical
      spectrum between AIH and PBC.

PMID- 12809934
TI  - Eta-1/osteopontin genetic polymorphism and primary biliary cirrhosis.
AB  - Early T-lymphocyte activation 1 (Eta-1)/osteopontin is a soluble ligand with
      pleomorphic immunologic activities including activation of macrophage chemotaxis,
      promotion of Th1 responses, and activation of B1 B-cells. A recent study
      suggested that a single-nucleotide polymorphism (SNP) at position nt 9250 (C to
      T) in exon 7 was highly associated with systemic lupus erythematosus (SLE). Eta
      1/osteopontin was reported to be highly expressed in the MRL/lpr mouse, which is
      recognized as one of the spontaneous autoimmune models of SLE. In the present
      study, we first investigated the association with this SNP and susceptibility to
      primary biliary cirrhosis (PBC). The allele frequencies of C/C, C/T, and T/T at
      position nt 9250 on the Eta-1/osteopontin gene in 50 PBC patients were 20, 32,
      and 48%, respectively, compared with 9, 47, and 44% in 34 healthy controls
      (P<0.16-0.72). The gene frequencies of C and T at this position in such PBC
      patients were 0.36 and 0.64, whereas those in the healthy controls were 0.32 and
      0.68 (P<0.91), respectively. Moreover, clinical findings and pathologic stages
      were not correlated with the variation of SNP. Those findings suggest no
      associations with Eta-1/osteopontin genetic polymorphism and susceptibility to
      PBC.

PMID- 12809935
TI  - Circulating KL-6 level at baseline is a predictive indicator for the occurrence
      of interstitial pneumonia during interferon treatment for chronic hepatitis C.
AB  - Interstitial pneumonia (IP) is a serious adverse event of interferon alpha
      (IFNalpha) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who
      received IFNalpha treatment with or without ribavirin between January 1992 and
      June 2002, six patients (1.1%) developed IP, including one patient who developed
      IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the
      onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum
      levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D),
      respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D
      levels were within the normal range in all seven cases, but the serum KL-6 level
      was elevated in five of the seven cases, contrasting with that in three of 48 age
      adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%;
      P=0.0003). Furthermore, the circulating KL-6 level at baseline was significantly
      higher among the seven cases than among the controls (543+/-105 vs. 304+/-98
      U/ml, P=0.0001). These results indicate that measurement of the circulating KL-6
      level in CH-C patients before IFN treatment may be useful for predicting the
      occurrence of IP during IFN treatment.

PMID- 12809936
TI  - Lens culinaris agglutinin-A-reactive alpha-fetoprotein as a marker for liver
      atrophy in fulminant hepatic failure.
AB  - Liver atrophy is frequently found at autopsy of patients with fulminant hepatic
      failure (FHF). Imaging studies in patients with FHF demonstrate that estimation
      of total liver volume correlates with prognosis. In this study, in order to
      determine serum markers for evaluating liver atrophy, we measured the weight of
      whole livers resected from 31 transplant recipients with FHF, and assessed the
      relation between the liver weights and several prognostic markers. The level of
      liver atrophy was evaluated by calculating the ratio of the removed whole liver
      weight to the body weight of each recipient, and 16 major variables including
      several serological markers were analyzed among those recipients. We found that
      the serum Lens culinaris agglutinin-A-reactive alpha-fetoprotein (AFP-L3) levels
      were significantly higher in patients with FHF than in those with other liver
      diseases. In FHF patients, the serum AFP-L3 level at the onset of encephalopathy
      was significantly higher in cases with mild atrophy than in those with severe
      atrophy (P<0.05). Notably, the residual liver volume was significantly correlated
      with the serum AFP-L3 level (Pearson's correlation coefficient=0.63), but not
      with AFP. In conclusion, AFP-L3 is a possible serum marker for evaluating liver
      atrophy and/or liver regeneration in patients with FHF.

PMID- 12809937
TI  - Inactivation of porcine endogenous retrovirus by human serum as a function of
      complement activated through the classical pathway.
AB  - BACKGROUND: The clinical use of organs and cells of pig donors as a source of
      tissue for xenotransplantation and extracorporeal therapies has been problematic
      due to the risk for zoonotic infection of porcine endogenous retroviruses (PERV).
      METHODS: The effect of human serum on PERV was evaluated using an infectivity
      assay and virolysis assay. Cell-free PERV infection to human 293 cells was
      determined by the presence of proviruses 5 days post-infection by a highly
      sensitive nested PCR, and the lysis of PERV virions was determined by the reverse
      transcriptase activities released into the supernatant. RESULTS: Treatment of
      PERV-PK, the culture supernatant of a pig kidney cell line containing the virus
      titer of 10(2.8) TCID(50) units/ml, with a quarter volume of human serum
      completely inactivated the infectivity. This activity was heat-labile and
      sensitive to an anti-complement agent, nafamostat mesilate, and a Ca(2+)
      chelator, EGTA, indicating the crucial involvement of complement activated
      through the classical pathway. Since a synthetic galactosyl alpha1-3 galalactose
      (Galalpha1-3Gal) largely absorbed the activity from the serum, natural antibodies
      to the Galalpha1-3Gal epitopes are likely to trigger the complement activation.
      CONCLUSION: Cell-free PERV seems no longer be infectious in human serum. This
      greatly encourages the clinical application of pig tissues in particular for
      extracorporeal therapies such as a bioartificial liver, in which pig cells do not
      come in direct contact with a recipient.

PMID- 12809938
TI  - Unusual hyperbilirubinemia associated with bacterial pneumonia and acute myeloid
      leukemia.
AB  - A 77-year-old man with pneumonia associated with acute myeloid leukemia was
      introduced to the hepatology unit at our hospital for hyperbilirubinemia. He had
      been suffering from a high fever because of pneumonia. He was icteric and his
      serum concentrations of total and direct bilirubin were 13.1 and 7.9 mg/dl,
      respectively. However, the other standard biochemical examinations for hepatic
      function, such as serum concentrations of aspartate aminotransferase, alanine
      aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase were
      normal except for lactate dehydrogenase. Lactate dehydrogenase isoenzyme analysis
      revealed that the high concentration was derived from leukemia cells.
      Ultrasonography of the abdomen revealed no abnormality in the liver or biliary
      tract. Administration of antibiotics for pneumonia decreased the serum bilirubin
      concentration, however, he died because of respiratory failure caused by the
      progression of pneumonia at 33 days after the admission. It was suggested that a
      disturbance in the bilirubin metabolism without hepatocyte necrosis or mechanical
      cholestasis might be involved in the pathogenesis of hyperbilirubinemia in
      patients with infectious diseases.

PMID- 12809939
TI  - Genotypic analysis of hepatitis B virus from patients with fulminant hepatitis:
      comparison with acute self-limited hepatitis.
AB  - AIM/BACKGROUND: There is an increasing evidence that certain hepatitis B virus
      (HBV) strains may contribute to the pathogenesis of fulminant hepatitis B (FHB).
      Recently, we reported that genotypes of HBV influence the clinical course of
      acute self-limited hepatitis B (AHB). In this study, we compared clinical
      features of FHB between different HBV genotypes and compared the prevalence of
      each genotype between FHB and AHB patients. METHODS: The subjects consisted of
      seven patients with FHB and 25 patients with AHB. The core promoter and precore
      region were directly sequenced following polymerase chain reaction, and genotype
      was determined by restriction fragment length polymorphism analysis of the S
      gene. RESULTS: Of the seven FHB patients, one had genotype A, one had genotype B,
      four had genotype C, and one had genotype D. Six of the seven FHB patients were
      infected by heterosexual contact; one FHB patient who was not infected by
      heterosexual contact had genotype C. All four FHB patients with genotype C had a
      short duration clinical course. In one patient with genotype A, the time from
      onset of hepatitis to hepatic coma was 30 days. These results are similar to
      those of the patients with AHB, in which clinical course was longer in patients
      with genotype A than in patients with genotype C. CONCLUSION: Viral genotype can
      be used to predict the clinical course of both FHB and AHB.

PMID- 12809940
TI  - Detection of serum hepatitis B virus DNA by real-time quantitative polymerase
      chain reaction (TaqMan PCR) during lamivudine treatment: comparison with three
      other assays.
AB  - Monitoring of hepatitis B virus (HBV) levels in serum plays an important role in
      the management of chronic hepatitis B in patients receiving lamivudine. We
      evaluated the usefulness of real-time quantitative polymerase chain reaction
      (TaqMan PCR) for the measurement of HBV DNA. The subjects were 22 patients with
      chronic hepatitis B treated with lamivudine for 4-12 months. HBV DNA was measured
      by TaqMan PCR. For comparison, HBV DNA was also measured in 88 sera by branched
      DNA (bDNA) assay, transcription-mediated amplification (TMA) assay, and Amplicor
      monitor test. Correlation was significant between the results of TaqMan PCR and
      those of the three other assays (r=0.630, 0.681, and 0.715, respectively;
      P<0.05). Of the 22 patients, HBV DNA was beneath the detection limit at the start
      of therapy in 4 (18%) on the bDNA assay, 3 (14%) on the TMA assay, 2 (9%) on the
      Amplicor test, and 0 (0%) on TaqMan PCR. Of the 19 patients for whom sera were
      available at 12 weeks of therapy, HBV DNA was not detected in 16 (84%) on the
      bDNA assay, 12 (63%) on the TMA assay, 6 (32%) on the Amplicor test, and 2 (11%)
      on TaqMan PCR. Tyrosine-methionine-aspartate-aspartate (YMDD) variants emerged in
      three patients; TaqMan PCR detected HBV DNA throughout treatment and revealed
      significantly increased viral loads before biochemical breakthrough. We conclude
      that monitoring of HBV by TaqMan PCR is useful for evaluating response to
      lamivudine treatment and for early detection of drug-resistant variants.

PMID- 12809941
TI  - Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol,
      acetaldehyde or lipopolysaccharide.
AB  - The aim of this work was to study the induction and secretion of interleukin 8
      (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde
      (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated
      with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and
      secretion were determined in the presence of the toxics, and the effect of
      antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was
      evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis
      factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide
      dismutase and glutathione peroxidase activities were determined. Lipid
      peroxidation increased significantly only in Ac-treated cells. All toxics failed
      to decrease significantly the intracellular levels of reduced GSH. Catalase
      activity was diminished in all treatments, while other enzyme activities did not
      present changes. No change in peroxide production was found with any treatment.
      IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant
      and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)
      treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase
      chain reaction results correlated with secretion values. Our results show that Ac
      and LPS treatment produced an increased IL-8 induction and secretion. Oxidative
      stress and TNF-alpha are mediators in IL-8 response. This observation suggests
      that in the in vivo liver, the mechanism of ethanol-induced IL-8 production
      requires ethanol metabolism, and hepatocytes do not require the interaction among
      different populations of liver cells to respond.

PMID- 12809942
TI  - Portal vein invasion and intrahepatic micrometastasis in small hepatocellular
      carcinoma by gross type.
AB  - Background/AIMS: Recurrence due to clinically undetectable intrahepatic
      metastasis and portal vein invasion of HCC cells is not 'uncommon' even in small
      HCCs. The present study investigated the relationship between these factors and
      macroscopic types of HCC. METHODS: Surgically resected 209 cases of small HCC
      less than 3 cm in diameter were examined. Macroscopically, 209 cases were divided
      into 'vaguely nodular type', 'single nodular type', 'single nodular type with
      extranodular growth' and 'confluent multinodular type'. RESULTS: None of the
      vaguely nodular type had intrahepatic metastasis or portal vein invasion, and
      their diameter was significantly smaller than the other three types. 'Single
      nodular type with extranodular growth' and 'confluent multinodular type' show
      higher frequency of portal vein invasion and intrahepatic metastases than 'single
      nodular type'. Among 149 metastatic lesions, the distance was 10 mm or shorter in
      118 (79.2%). CONCLUSIONS: It is important to precisely determine the gross type
      of small HCC by diagnostic imaging in order to predict portal vein invasion and
      micrometastasis. It is also important to ablate the tumor with enough surrounding
      tissue 1 cm in width at least to prevent the recurrence from those
      micrometastasis.

PMID- 12809943
TI  - Induction of donor-specific tolerance to allogeneic hepatocytes by allogeneic
      bone marrow transplantation.
AB  - Allogenic hepatocytes are rejected within a few days after transplantation
      without immunosuppression. We previously showed that the peripheral tolerance did
      not effectively prolong the survival of allogeneic hepatocytes transplanted in
      the spleen, because anergic T cells lysed allogeneic hepatocytes through Fas/Fas
      ligand system. The aim of this study was to address whether or not the central
      tolerance induced by allogeneic bone marrow transplantation (BMT) allows
      transplanted hepatocytes to survive in the spleen of the recipient. Bone marrow
      cells obtained from C57BL/6 (B6) donor mice were injected intravenously into
      lethally irradiated BALB/c recipients. Ninety percent of the recipient mice were
      able to survive more than 30 days, although all of the non-BMT controls died
      within 12 days. Full donor chimerism was observed in the recipient. Then
      hepatocytes from B6 mice were transplanted into the spleen of BALB/c mice at 30
      days post-BMT. The transplanted donor-hepatocytes were able to survive for over 7
      days, while those from third-party mice (C3H/He) were rejected within a few days.
      These findings demonstrate that donor-specific tolerance was induced by
      allogeneic BMT. Furthermore, the induction of central tolerance, but not
      peripheral tolerance, may be a useful strategy for prolonging the survival of
      allogeneic hepatocytes in the spleen.

PMID- 12809944
TI  - AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis.
AB  - The majority of Caucasian patients with hemochromatosis are homozygous for C282Y
      mutation of the HFE gene. In contrast to its high prevalence in Caucasians,
      hemochromatosis is a rare disorder in Japan. This may be due to the low
      prevalence of the C282Y mutation of the HFE gene in Japanese. Recent reports
      suggest that the mutations of transferrin receptor 2 (TfR2) gene may be involved
      in non-HFE hemochromatosis. Therefore, we investigated the TfR2 gene of 6
      sporadic and 5 familiar cases of Japanese hemochromatosis. Three siblings in one
      family were found to be homozygous for an AVAQ 594-597 deletion. All three had
      severe iron deposits in the hepatocytes and bile ducts, but none was affected by
      diabetes mellitus. This mutation was not detected in 100 control individuals.
      Further study was undertaken to investigate whether the large deletion of the
      TfR2 gene is the mutation responsible for some of the Japanese hemochromatosis
      cases.

PMID- 12809945
TI  - Unique reciprocal changes of hepatocellular membrane transporter expression and
      fluidity in rats with selective biliary obstruction.
AB  - BACKGROUND AND AIMS: The localized occlusion of bile ducts by
      intrahepaticlithiasis and intrahepatic neoplasms dose not cause severe jaundice,
      although the reason is unclear. The aim of this study was to clarify the
      molecular change of the liver in partial cholestasis, especially with respect to
      transporter expression (Mrp2, Mrp3, Bsep, P-gps) and membrane fluidity. METHODS
      AND RESULTS: After 3 days of selective bile duct ligation in Sprague-Dawley rats,
      the obstructed lobe (OL) and non-OL were analyzed. Canalicular and sinusoidal
      membrane fluidity were decreased in the OL compared with the non-OL. Mrp2 protein
      expression was significantly lower in the OL (by 62.9+/-6.9%) when compared with
      the non-OL. Mdr1b and Mdr2 mRNA were up-regulated in the OL when compared with
      the non-OL. Interestingly, Mrp3 protein and mRNA were induced in both the non-OL
      and OL of rats without hyperbilirubinemia. CONCLUSIONS: It seems that the
      reduction of membrane fluidity in the OL is a local response to localized
      cholestasis, while the induction of Mrp3 observed in both the OL and non-OL may
      be a response of the whole liver to localized impairment of bile secretion,
      although the regulatory mechanism is yet to be established.

PMID- 12809946
TI  - Jun N-terminal kinase activation and upregulation of p53 and p21(WAF1/CIP1) in
      selenite-induced apoptosis of regenerating liver.
AB  - To investigate apoptosis induced by selenite in hepatocytes in vivo, rats
      received a single injection of sodium selenite immediately after partial
      hepatectomy. Characteristic DNA fragmentation in gel electrophoresis and in situ
      end-labeling and the increase in caspase-3 activity were observed at 4 h after
      partial hepatectomy with selenite injection. The activation of Jun N-terminal
      kinase (JNK) was observed as early as 15 min and increased to about 10-fold the
      maximal level of the control at 1 and 2 h after partial hepatectomy in selenite
      injected rats, while a transient increase was observed at 1 h in the control.
      Western blot analysis revealed that the c-Jun and the phosphorylated c-Jun
      protein markedly increased after 30 min and reached a maximal level at 1 and 2 h
      after partial hepatectomy with selenite injection, although c-Jun and a faint
      band of the phosphorylated c-Jun were observed after 1 h in the control. The
      levels of c-jun mRNA and c-Fos protein and mRNA in selenite-injected rats also
      increased more than in the control. The rise in the p53 protein level after
      partial hepatectomy with selenite injection was followed by the upregulation of
      p21(WAF1/CIP1) mRNA and protein expression. These results suggested that selenite
      induced apoptosis accompanied by the activation of caspase-3 and JNK and the
      upregulation of c-jun, c-fos, p53 and p21(WAF1/CIP1) at the early stage of liver
      regeneration.

PMID- 12809947
TI  - The anthelmintic levamisole is an allosteric modulator of human neuronal
      nicotinic acetylcholine receptors.
AB  - L-[-]-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1b]-thiazole hydrochloride
      (levamisole) is an anthelmintic that targets the nicotinic acetylcholine
      receptors of parasitic nematodes. We report here the effects of levamisole on
      human neuronal alpha 3 beta 2 and alpha 3 beta 4 nicotinic receptors,
      heterologously expressed in Xenopus oocytes and studied with the voltage clamp
      method. Applied alone, levamisole was a very weak partial agonist for the two
      subunit combinations. When co-applied with acetylcholine, micromolar
      concentrations of levamisole potentiated responses, while millimolar
      concentrations inhibited them; these effects were complex functions of both
      acetylcholine and levamisole concentrations. The differences in the levamisole
      effects on the two receptor combinations suggest that the effects are mediated by
      the beta subunit. Several combinations of agonist and anthelmintic gave the dual
      potentiation/inhibition behavior, suggesting that the modulatory effects are
      general. Levamisole inhibition showed macroscopic characteristics of open channel
      block. Several results led us to conclude that levamisole potentiation occurs
      through noncompetitive binding to the receptor. We propose pseudo-site binding
      for noncompetitive potentiation by levamisole.

PMID- 12809948
TI  - Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor
      ligand, in forced swimming test.
AB  - This study examined the effects of peripheral-type benzodiazepine receptors in
      the forced swimming test. PK 11195 (1-(2-chloro-phenyl)-N-methyl-N-(1
      methylpropyl)-1-isoquinoline carboxamide) and Ro5-4864 (7-chloro-5-(4
      chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine-2-one) were i.p.
      injected in mice, according to an acute (1 or 24 h) and a repeated (14 days)
      schedule. Pretreatment with the agonist, Ro5-4864, significantly reduced
      immobility time 1 h after treatment but not 24 h after it, whereas the
      antagonist, PK11195, did not interfere with the test parameters. Nevertheless,
      PK11195 pretreatment inhibited the Ro5-4864 antidepressant-like effect. Animals
      repeatedly treated with Ro5-4864 had a similar profile of action with no sign of
      motor impairment or locomotor activation as evaluated in the rota-rod and open
      field tests, respectively. Aminoglutethimide pretreatment, which blocks the early
      step of steroid synthesis, inhibited the antidepressant-like effect of Ro5-4864.
      The present findings suggest an antidepressant-like profile for the
      benzodiazepine, Ro5-4864, that seems to involve steroid synthesis as underlying
      mechanism.

PMID- 12809949
TI  - Involvement of presynaptic 5-HT(1A) and benzodiazepine receptors in the
      anticonflict activity of 5-HT(1A) receptor antagonists.
AB  - In the present paper, we examined the effect of lesions of 5-hydroxytryptamine (5
      HT) neurons, produced by p-chloroamphetamine (p-CA; 2 x 10 mg/kg), and the
      influence of flumazenil (Ro 15-1788, 10 mg/kg), a benzodiazepine receptor
      antagonist, on the anticonflict activity of N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) and trans-1
      (2-methoxy-phenyl)-4-[4-succinimidocyclohexyl]piperazine (MP 349), pre- and
      postsynaptic 5-HT(1A) receptor antagonists, and 1-(2-methoxyphenyl)-4-(4
      succinimidobutyl)piperazine (MM 77), a postsynaptic 5-HT(1A) receptor antagonist,
      in the Vogel conflict drinking test in rats. Diazepam was used as a reference
      compound. WAY 100635 (0.5-1 mg/kg), MP 349 (0.25-0.5 mg/kg), MM 77 (0.03-0.25
      mg/kg) and diazepam (2.5-5 mg/kg) significantly increased the number of shocks
      accepted during experimental sessions in the conflict drinking test. In p
      chloroamphetamine-pretreated rats, neither WAY 100635 (1 mg/kg) nor MP 349 (0.25
      mg/kg) induced an anticonflict effect, whereas MM 77 (0.06 mg/kg) did produce it.
      Flumazenil fully blocked the anticonflict effects of WAY 100635 (1 mg/kg) and
      diazepam (5 mg/kg), and it partly but significantly reduced the anticonflict
      effects of MP 349 (0.25 mg/kg) and MM 77 (0.06 mg/kg). p-Chloroamphetamine and
      flumazenil alone were inactive in the conflict drinking test. The present results
      suggest that, first, the anticonflict effect of the 5-HT(1A) receptor
      antagonists, WAY 100635 and MP 349, but not MM 77, is linked to the
      presynaptically located 5-HT(1A) receptors, and second, benzodiazepine receptors
      are indirectly involved in such effects of WAY 100635, MP 349 and MM 77, due
      maybe to a possible interaction between the 5-HT and the gamma-aminobutyric acid
      (GABA)/benzodiazepine systems.

PMID- 12809950
TI  - Role of K(+) channels in the coronary and renal vascular reactivity to
      vasopressin in diabetic rats.
AB  - To study the role of K(+) channels in the coronary and renal vascular response to
      vasopressin during diabetes mellitus, and whether there are gender differences in
      this role, we have examined the isometric response to this peptide of 2-mm-long
      arterial segments from male and female, normoglycemic and streptozotocin-induced
      diabetic rats. Vasopressin (10(-12)-3 x 10(-8) M) produced arterial concentration
      dependent contraction, and during normoglycemia, this contraction was lower in
      coronary arteries from female than from male rats, and it was similar in renal
      arteries from both genders. This contraction was reduced by diabetes in coronary
      arteries, and increased in renal arteries, from both genders. The blocker of
      Ca(2+)-sensitive K(+) channels charybdotoxin (10(-7) M) increased the contraction
      to vasopressin in coronary arteries of diabetic females, but not in the other
      cases (diabetic males and normoglycemic females or males). This blocker also
      increased the contraction to vasopressin in renal arteries from diabetic, but not
      in those from normoglycemic female rats, and also increased it in a higher
      magnitude in arteries from diabetic than in those from normoglycemic male rats.
      The blocker of ATP-sensitive K(+) channels glybenclamide (10(-5) M) or the
      scavenger of superoxide radicals superoxide dismutase (100 U/ml) did not modify
      the contraction to vasopressin in any experimental group. These results suggest
      that diabetes activates the modulatory role of K(+) channels in the coronary and
      renal vasoconstriction to vasopressin, but it alters in a different way the
      vasoconstriction to vasopressin in these two types of arteries. The effects of
      diabetes on this vasoconstriction are not related to increased release of
      superoxide radicals.

PMID- 12809951
TI  - Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in
      postinfarcted rat myocardium.
AB  - The present study was designed to investigate the effects of dantrolene on
      intracellular Ca(2+) ([Ca(2+)](i)) handling and inotropy in rat infarcted
      myocardium. Dantrolene-treated rats with myocardial infarction were placed into
      two different dosage groups. The infarcted control group received placebo only.
      Isometric contractility and intracellular Ca(2+) transients were recorded
      simultaneously in isolated papillary muscles. Diastolic [Ca(2+)](i) was
      significantly lower in muscle preparations from infarcted rats receiving
      dantrolene compared to the placebo control group. Additionally, treatment with
      dantrolene in infarcted rats significantly improved the inotropic response to 10(
      4) M isoproterenol. The protein levels of the sarcoplasmic reticulum Ca(2+)
      ATPase were increased in infarcted rat hearts with dantrolene treatment. We
      conclude that dantrolene improved the inotropic response to beta-adrenoceptor
      stimulation in rat postinfarcted myocardium, which is related to improved
      intracellular Ca(2+) handling, and lowered diastolic Ca(2+) concentration.

PMID- 12809952
TI  - Actions of galanin on neurotransmission in the submucous plexus of guinea pig
      small intestine.
AB  - Electrophysiologic recording methods were used to study the actions of galanin on
      synaptic transmission in the submucous plexus of guinea pig ileum. Exposure to
      galanin resulted in concentration-dependent suppression of slow noradrenergic
      inhibitory postsynaptic potentials and fast nicotinic excitatory postsynaptic
      potentials in the majority of neurons. Failure of galanin to suppress nicotinic
      depolarizing responses to micropressure pulses of acetylcholine and failure to
      suppress hyperpolarizing responses to micropressure pulses of norepinephrine
      suggested that galanin acted at presynaptic inhibitory receptors to suppress
      release of acetylcholine and norepinephrine. Galanin suppressed slow excitatory
      postsynaptic potentials in eight of eight neurons with AH (after
      hyperpolarization) type electrical behavior and in none of 26 neurons with S
      (synaptic) type electrical behavior. Suppression of excitatory neurotransmission
      in AH neurons was always associated with membrane hyperpolarization. Excitatory
      responses caused by experimentally applied substance P were also inhibited by
      galanin. Galanin-(1-16) and galanin-like peptide mimicked the inhibitory actions
      of galanin on neurotransmission. The selective galanin GAL2 receptor agonist [D
      Trp(2)]galanin was inactive. The chimeric peptides, galanin-(1-13)-spantide I,
      galantide, galanin-(1-13)-neuropeptide Y(25-36) amide, galanin-(1-13)-bradykinin
      (2-9)amide and galanin-(1-13)-Pro-Pro-Ala-Leu-Ala-Leu-Ala amide all produced
      varying degrees of suppression of the synaptic potentials. The evidence suggests
      that the galanin GAL1 receptor, but not the galanin GAL2 receptor, mediated the
      presynaptic and postsynaptic inhibitory actions of galanin.

PMID- 12809953
TI  - Gastroprotective effects of phenylpropanoids from the rhizomes of Alpinia galanga
      in rats: structural requirements and mode of action.
AB  - The effects of 1'S-1'-acetoxychavicol acetate and related phenylpropanoids
      isolated from the rhizomes of Alpinia galanga on ethanol-induced gastric lesions
      in rats were examined. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'
      acetoxyeugenol acetate markedly inhibited the ethanol-induced gastric mucosal
      lesions (ED(50)=0.61 and ca. 0.90 mg/kg). In addition, 1'S-1'-acetoxychavicol
      acetate inhibited the lesions induced by 0.6 M HCl (ED(50)=0.73 mg/kg) and
      aspirin (ED(50)=0.69 mg/kg) but it did not show a significant effect on
      indomethacin-induced gastric lesions and acid output in pylorus-ligated rats at
      doses of 0.5-5.0 mg/kg. From the gastroprotective effects of various related
      compounds, the 1'-acetoxyl group of 1'S-1'-acetoxychavicol acetate and 1'S-1'
      acetoxyeugenol acetate was found to be essential for their strong activity. With
      regard to the mode of action, the gastroprotective effects of 1'S-1'
      acetoxychavicol acetate were attenuated by pretreatment with indomethacin and N
      ethylmaleimide, and 1'S-1'-acetoxychavicol acetate significantly increased the
      glutathione levels of gastric mucosa in rats. These findings suggest that
      endogenous prostaglandins and sulfhydryl compounds are involved in the protective
      effect of 1'S-1'-acetoxychavicol acetate.

PMID- 12809954
TI  - Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative, S-2E.
AB  - A newly synthesized benzoic acid derivative, (+)-(S)-p-[1-(p-tert-butylphenyl)-2
      oxo-4-pyrrolidinyl]methoxybenzoic acid (S-2E), has the capacity to inhibit the
      biosynthesis of both sterol and fatty acids. Here, we report the mechanism by
      which S-2E lowers blood cholesterol and triglyceride levels. In the liver, S-2E
      was converted into its active metabolite, S-2E-CoA. S-2E-CoA noncompetitively
      inhibited the enzymatic activities of both 3-hydroxy-3-methylglutaryl coenzyme-A
      (HMG-CoA) reductase and acetyl-CoA carboxylase at K(i)=18.11 microM and K(i)=69.2
      microM, respectively. Interestingly, pharmacokinetic experiments in rats showed
      that the concentration of S-2E-CoA in the liver was sufficient to inhibit the
      activities of HMG-CoA reductase and acetyl-CoA carboxylase, for example, when
      orally given to rats at 10 mg/kg. Indeed, S-2E (3-30 mg/kg) given orally
      suppressed the secretion rate of very-low-density lipoprotein (VLDL)-cholesterol
      and triglyceride in Triton WR-1339-injected rats. Furthermore, S-2E lowered the
      blood total cholesterol and triglyceride levels simultaneously in Zucker fatty
      rats. Collectively, S-2E may be useful in the treatment of familial
      hypercholesterolemia and mixed hyperlipidemia.

PMID- 12809956
TI  - Olmesartan medoxomil: an angiotensin II-receptor blocker.
AB  - BACKGROUND: Regulation of the activity of the renin-angiotensin-aldosterone
      system has become important in the management of cardiovascular disease.
      Olmesartan medoxomil (CS-866) is the newest selective angiotensin II-receptor
      blocker (ARB) to be approved for the treatment of hypertension. OBJECTIVE: This
      review describes the mechanism of action, pharmacokinetics, adverse-effect
      profile, drug-interaction potential, and dosing of olmesartan medoxomil. The
      results of relevant clinical efficacy and safety trials are also discussed.
      METHODS: This review is based on data from published clinical efficacy and safety
      trials and abstracts of conference presentations. To identify appropriate English
      language publications for review, MEDLINE (1966-October 2002) and EMBASE (1990
      2002) were searched using the terms olmesartan medoxomil, CS-866, angiotensin II
      receptor blocker, and hypertension. RESULTS: Olmesartan medoxomil has been
      reported to be an effective agent for the treatment of hypertension. Its blood
      pressure-lowering effects were comparable to those of other antihypertensive
      agents and other ARBs. Effects were seen as early as 2 weeks and persisted when
      olmesartan medoxomil was administered long term (for 1 year). The maximum
      recommended daily dose is 40 mg, except in the presence of severe renal
      insufficiency (creatinine clearance <20 mL/min) or moderate hepatic insufficiency
      (Child-Pugh score 7-9), when the daily dose should not exceed 20 mg. Olmesartan
      medoxomil was well tolerated. The most commonly reported adverse effect occurring
      significantly more often with olmesartan medoxomil than with placebo was
      dizziness (seen in approximately 3% of patients). The occurrence of clinically
      significant drug interactions was minimal. CONCLUSIONS: Based on the available
      literature, olmesartan medoxomil is an effective ARB for the treatment of
      hypertension, with a favorable adverse-effect and drug-interaction profile.

PMID- 12809957
TI  - Efficacy of a low-dose regimen of cyclobenzaprine hydrochloride in acute skeletal
      muscle spasm: results of two placebo-controlled trials.
AB  - BACKGROUND: Cyclobenzaprine hydrochloride is a muscle relaxant that is effective
      in improving muscle spasm, reducing local pain and tenderness, and increasing
      range of motion in acute, painful musculoskeletal conditions. Sedation is the
      most common adverse event associated with its use at the usual dosage of 10 mg
      TID. Studies in healthy adults suggest that a lower dose may produce less
      sedation. Because cyclobenzaprine's duration of action is 4 to 6 hours, reducing
      the dosing frequency to 10 mg BID would create a potentially painful untreated
      interval between doses. The alternative is administration of a lower dose (eg, 5
      or 2.5 mg) TID. OBJECTIVE: These studies were designed to assess the efficacy and
      tolerability of cyclobenzaprine 2.5, 5, and 10 mg TID compared with placebo in
      patients with acute musculoskeletal spasm. METHODS: In 2 randomized, double
      blind, placebo-controlled, parallel-group trials conducted at primary care
      centers in the United States, adult patients with acute painful muscle spasm of
      the lumbar or cervical region were randomly assigned to receive treatment with
      2.5, 5, or 10 mg cyclobenzaprine TID or placebo for 7 days (study 1:
      cyclobenzaprine 5 or 10 mg TID or placebo; study 2: cyclobenzaprine 2.5 or 5 mg
      TID or placebo). The primary efficacy measures were patient-rated clinical global
      impression of change, medication helpfulness, and relief from starting backache.
      Neither study included a nonsteroidal anti-inflammatory drug (NSAID) as an active
      control. Although physicians frequently prescribe an analgesic or NSAID in
      addition to cyclobenzaprine, these studies were not designed to assess whether
      adding cyclobenzaprine provides a benefit over that of an analgesic. RESULTS: One
      thousand four hundred five patients (737 study 1; 668 study 2), two thirds with
      low back pain and one third with neck pain, were randomized to treatment. Their
      mean age was 42 years, and approximately 89% were white. In both studies,
      patients receiving cyclobenzaprine 5 or 10 mg had significantly higher mean
      scores on the primary efficacy measures compared with those receiving placebo
      (study 1-P</=0.001 cyclobenzaprine 5 and 10 mg vs placebo, all measures at visits
      2 and 3; study 2-P</=0.03 cyclobenzaprine 2.5 mg vs placebo, relief from starting
      backache on day 3 only; cyclobenzaprine 5 mg vs placebo, patient-rated clinical
      global impression of change, medication helpfulness, and relief from starting
      backache at visit 3 or day 7 only). On day 7, significantly more patients
      receiving cyclobenzaprine 5 or 10 mg reported relief compared with placebo
      recipients (P < 0.05 all cyclobenzaprine groups vs placebo). Onset of relief was
      apparent within 3 or 4 doses of the 5-mg regimen. In the subanalysis of the
      proportion of responders in the pooled 5-mg groups who did and did not report
      somnolence, a meaningful treatment effect was observed on all primary efficacy
      variables in patients who did not report somnolence, suggesting that efficacy was
      independent of sedation. Cyclobenzaprine was well tolerated. Somnolence and dry
      mouth, the most common adverse effects, were mild and dose related. Overall, >/=
      1 adverse event was reported in 54.1%, 61.8%, and 35.4% of patients receiving
      cyclobenzaprine 5 or 10 mg or placebo, respectively, in study 1 and by 43.9%,
      55.9%, and 35.4% of patients receiving cyclobenzaprine 2.5 or 5 mg or placebo,
      respectively, in study 2. Adverse events were the primary reason for
      discontinuation of treatment in the cyclobenzaprine 5- and 10-mg groups in both
      studies. In study 2, ineffectiveness of therapy was the main reason for
      discontinuation of therapy in the group receiving cyclobenzaprine 2.5 mg.
      CONCLUSIONS: Cyclobenzaprine 2.5 mg TID was not significantly more effective than
      placebo. The cyclobenzaprine 5- and 10-mg TID regimens were associated with
      significantly higher mean efficacy scores compared with placebo. Cyclobenzaprine
      5 mg TID was as effective as 10 mg TID, and was associated with a lower incidence
      of sedation.

PMID- 12809958
TI  - A randomized, double-blind, placebo-controlled, clinical trial of the effects of
      pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic
      medication-naive patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: The goal of this study was to compare the effects of 2 doses of
      pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo
      on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in
      patients with type 2 diabetes mellitus who had suboptimal glycemic control and
      mild dyslipidemia. METHODS: Patients with type 2 diabetes mellitus (HbA(1c)
      >/=6.5% and </=9.8%) who had not previously received insulin or oral
      antihyperglycemic medications (OAMs) were randomized to treatment with placebo,
      pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16
      weeks at 41 centers in Canada and Spain. RESULTS: A total of 297 patients were
      randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was
      58.4 (10.9) years (range, 24-85 years), mean (SD) body mass index was 31.4 (4.8)
      kg/m(2), mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months,
      and 30.6% of patients were receiving medication for dyslipidemia. Treatment with
      pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA(1c) by 0.8% and 0.9%
      from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction
      in HbA(1c) of 0.2% was observed in the placebo group (P = 0.025). In patients
      with medium (>/=7% to <8%) or high (>/=8% to </=9.8%) baseline HbA(1c), both
      doses of pioglitazone significantly reduced HbA(1c) (both P < 0.001 vs placebo).
      Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus
      placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity
      by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001,
      respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly
      increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P < 0.001,
      respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P <
      0.001, respectively). Pioglitazone 45 mg also significantly reduced serum
      triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo
      (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg
      were associated with a significant reduction in serum alanine aminotransferase
      relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone
      appeared to be safe and was well tolerated. CONCLUSIONS: In the present study,
      pioglitazone 30 and 45 mg produced significant improvements in HbA(1c), insulin
      sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes
      mellitus with suboptimal glycemic control and mild dyslipidemia.

PMID- 12809959
TI  - A combined analysis of two studies assessing the ocular comfort of antiallergy
      ophthalmic agents.
AB  - BACKGROUND: Many topical agents with similar efficacies are available for the
      treatment of ocular allergies. In addition to efficacy, comfort is an important
      criterion because it affects overall patient satisfaction, compliance, and in
      turn efficacy. OBJECTIVE: The goal of this study was to compare the comfort
      profiles of permirolast, ketorolac, cromolyn, and nedocromil ophthalmic solutions
      using combined results from 2 separate clinical trials. METHODS: Two clinical
      trials were conducted. Adults with asymptomatic eyes were included in the first
      study. In this single-center, 7-day, prospective, double-blind, single-dose,
      crossover, parallel-group study, subjects were randomized to be bilaterally dosed
      with pemirolast, cromolyn, or ketorolac at each of 3 visits. Study 2 was a single
      center, 1-day, prospective, randomized, double-blind, single-dose, contralateral,
      active-control study in which subjects received pemirolast in 1 eye and
      nedocromil in the contralateral eye. In both studies, subjects completed a pre-
      and postinstillation ocular comfort questionnaire: the primary variable was
      overall ocular discomfort, measured on a 4-point scale original to these studies
      (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Half-increments were permitted.
      Secondary variables included burning/stinging, foreign-body sensation, tearing,
      and photophobia. RESULTS: Forty-five subjects (29 women, 16 men; mean [SD] age,
      35.9 [12.6] years) were enrolled in study 1; 48 subjects (30 women, 18 men; mean
      [SD] age, 33.6 [10.2] years) were enrolled in study 2. In study 1, overall
      discomfort was significantly lower with pemirolast than with cromolyn (P = 0.001)
      or ketorolac (P < 0.001). In terms of overall discomfort, the number of subjects
      with a clinically significant increase (>/=1 unit) in score was significantly
      lower with pemirolast compared with ketorolac (P = 0.021). Burning/stinging and
      tearing were also significantly lower with pemirolast than with cromolyn (P <
      0.001 and P = 0.014, respectively). Mean changes in score compared with
      preinstillation were consistently lower with pemirolast than with cromolyn for
      both burning/stinging (P < 0.001) and tearing (P = 0.014). In study 2, overall
      discomfort was significantly lower with pemirolast than with nedocromil (P <
      0.001). The number of subjects with a clinically significant increase in overall
      discomfort score was significantly lower with pemirolast than with nedocromil (P
      = 0.007). No changes in ocular tolerability parameters were reported in either
      study. CONCLUSION: In these single-dose studies, pemirolast was found to be
      significantly more comfortable than cromolyn, ketorolac, or nedocromil.

PMID- 12809960
TI  - Randomized, double-blind, placebo-controlled comparison of the action of
      orlistat, fluvastatin, or both an anthropometric measurements, blood pressure,
      and lipid profile in obese patients with hypercholesterolemia prescribed a
      standardized diet.
AB  - OBJECTIVE: The aim of this study was to assess obese patients with
      hypercholesterolemia whom were prescribed a standardized diet, comparing the
      action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on
      anthropometric measurements, blood pressure (BP), and lipid profile. METHODS:
      This was a 1-year, randomized, double-blind, placebo-controlled trial. The
      patients were prescribed a controlled-energy diet and were randomly allocated to
      receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or
      olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements
      (body weight, body mass index [BMI], waist circumference, and BP) and lipid
      profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol
      [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs])
      were performed at baseline and after 6 months and 1 year of treatment. RESULTS:
      The study included 99 obese patients with hypercholesterolemia (48 men and 51
      women; mean [SD] age, 51 [9] years). There were no significant differences
      between groups in baseline demographic, BP, or plasma lipid values. Three
      patients dropped out (2 women in the O group and 1 man in the OF group) due to
      adverse events related to orlistat treatment, including gastrointestinal events
      (oily spotting and fecal urgency). Ninety-six patients completed the study. There
      were significant differences from baseline (mean [SD]) in BMI, waist
      circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF
      group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P <
      0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0
      [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6]
      kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF
      group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P <
      0.01). Significant reductions from baseline in systolic and diastolic BP were
      observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P
      < 0.01). At 6 months, there were significant reductions from baseline in TC and
      LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P
      < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase
      in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction
      from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01,
      respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P
      < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was
      significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01,
      respectively). CONCLUSION: Improvements in clinical and lipid-profile parameters
      were found at 1 year with all 3 treatments.

PMID- 12809961
TI  - Tramadol/acetaminophen combination tablets for the treatment of chronic lower
      back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient
      study.
AB  - BACKGROUND: Tramadol and acetaminophen (APAP) have both shown efficacy in the
      treatment of lower back pain. The combination of these 2 agents has demonstrated
      synergistic analgesic action in animal models at specific ratios. OBJECTIVE: This
      study assessed the long-term (3-month) efficacy and safety of tramadol 37.5
      mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain.
      METHODS: Patients with at least moderate lower back pain (pain visual analog
      [PVA] score >/=40 mm on a 100-mm scale) were randomized to receive up to 8
      tablets of tramadol/APAP per day or placebo for 91 days. Medication was titrated
      from 1 to 4 tablets/d by day 10. The primary efficacy measure was PVA score at
      the final visit. Secondary measures included scores on the Pain Relief Rating
      Scale (PRRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Roland Disability
      Questionnaire (RDQ), and 36-Item Short-Form Health Survey (SF-36); the incidence
      of discontinuation due to insufficient pain relief (Kaplan-Meier analysis); and
      overall assessments of medication by the patients and investigators. RESULTS:
      Three hundred eighteen patients (161 tramadol/APAP, 157 placebo) were included in
      the intent-to-treat population, defined as all patients who took >/=1 dose of
      study medication and had >/=1 postrandomization efficacy measurement. The mean
      age of the study population was 53.9 years, 63.2% were female, 90.3% were white,
      and the mean baseline PVA score was 70.0 mm. There were no significant
      differences between groups at baseline. Tramadol/APAP significantly improved
      final PVA scores (P = 0.015) and final PRRS scores (P < 0.001) compared with
      placebo. Tramadol/APAP also significantly improved RDQ scores (P </= 0.027) and
      scores on many subcategories of the SF-MPQ, including total score (P = 0.021).
      The tramadol/APAP group had significant improvements on the role-physical (P =
      0.005), bodily pain (P = 0.046), role-emotional (P = 0.001), mental health (P =
      0.026), reported health transition (P = 0.038), and mental component summary (P =
      0.008) subscales of the SF-36. The cumulative incidence of discontinuation due to
      insufficient pain relief was 22.1% for tramadol/APAP and 41.0% for placebo (P <
      0.001). Treatment-emergent adverse events in the tramadol/APAP group included
      nausea (13.0%), somnolence (12.4%), and constipation (11.2%). CONCLUSIONS: In
      this study, tramadol 37.5 mg/APAP 325 mg combination tablets were effective and
      had a favorable safety profile in the treatment of chronic lower back pain.

PMID- 12809962
TI  - A comparison of granisetron, droperidol, and metoclopramide in the treatment of
      established nausea and vomiting after breast surgery: a double-blind, randomized,
      controlled trial.
AB  - BACKGROUND: Women undergoing breast surgery are at particular risk for post
      operative nausea and vomiting (PONV), with an incidence of emesis as high as 50%
      when no prophylactic antiemetic is used. OBJECTIVE: This study compared the
      efficacy of the selective 5-hydroxytryptamine(3) receptor antagonist granisetron
      with that of the traditional antiemetics droperidol and metoclopramide in the
      treatment of established PONV after breast surgery. METHODS: In this prospective,
      randomized, double-blind trial, patients who had undergone breast surgery and
      were experiencing PONV during the first 3 hours after anesthesia received either
      granisetron 40 microg/kg IV, droperidol 20 microg/kg IV, or metoclopramide 0.2
      mg/kg IV. Patients were observed for 24 hours after administration of study drug.
      Emetic episodes were recorded by nursing staff who were blinded to treatment
      assignment. RESULTS: Seventy-five patients were enrolled in the study, 25 in each
      treatment group. Their age ranged from 41 to 65 years. There were no significant
      between-group differences in patients' demographic or surgical characteristics at
      study entry. The number of patients who were emesis free (no nausea, retching, or
      vomiting) was significantly higher in patients who received granisetron (88%
      [2225]) than in those who received droperidol (64% [1625]; P = 0.047) or
      metoclopramide (56% [1425]; P = 0.013). In patients who experienced nausea (3, 8,
      and 9 patients in the granisetron, droperidol, and metoclopramide groups,
      respectively), the severity of nausea was significantly lower with granisetron
      compared with droperidol (P = 0.028) and metoclopramide (P = 0.025). No
      clinically serious adverse events were observed in any group. CONCLUSION:
      Granisetron was significantly more effective than the traditional antiemetics
      droperidol and metoclopramide for the treatment of PONV in this population of
      patients undergoing breast surgery.

PMID- 12809963
TI  - Differential effects of antipsychotic agents on the risk of development of type 2
      diabetes mellitus in patients with mood disorders.
AB  - BACKGROUND: Atypical antipsychotics are being used increasingly in the management
      of mood disorders. OBJECTIVE: The objective of this study was to investigate the
      association between exposure to antipsychotic therapy and newly reported type 2
      diabetes mellitus in patients with mood disorders. METHODS: Claims data for the
      period January 1996 through December 1997 were analyzed for patients with mood
      disorders in 2 large US health plans. Logistic regression models were used to
      determine the odds of reporting diabetes in patients exposed to risperidone,
      olanzapine, or high- or low-potency conventional antipsychotics compared with
      untreated patients, taking into account duration of treatment and dosage. Some of
      the covariates used in the models were concurrent use of antipsychotics, use of
      other psychotropic drugs, age, sex, and length of observation. RESULTS: Based on
      the claims data, 849 patients were exposed to risperidone, 656 to olanzapine, 785
      to high-potency conventional antipsychotics, and 302 to low-potency conventional
      antipsychotics; 2644 patients were untreated. The odds of newly reported type 2
      diabetes in patients who received risperidone were not significantly different
      from those in untreated patients (12-month odds ratio [OR] = 1.024; 95% CI, 0.351
      3.015). The odds in patients treated with high-potency conventional
      antipsychotics also did not differ significantly from those of untreated patients
      (12-month OR = 1.945; 95% CI, 0.794-4.786). Unlike patients who received
      risperidone or high-potency conventional antipsychotics, patients who received
      olanzapine (12-month OR = 4.289; 95% CI, 2.102-8.827) and low-potency
      conventional antipsychotics (12-month OR = 4.972; 95% CI, 1.967-12.612) had
      significantly higher odds for the development of type 2 diabetes compared with
      untreated patients. CONCLUSIONS: These findings suggest that some antipsychotics
      may increase the risk for the development of type 2 diabetes in patients with
      mood disorders and that the effect may vary by drug. In contrast to olanzapine
      and low-potency conventional antipsychotics, risperidone and high-potency
      conventional antipsychotics were not associated with an increased risk for
      development of type 2 diabetes in this patient population.

PMID- 12809964
TI  - Patient persistency with ocular prostaglandin therapy: a population-based,
      retrospective study.
AB  - BACKGROUND: Open-angle glaucoma affects an estimated 33 million individuals
      worldwide. An intraocular pressure >21 mm Hg in individuals with no evidence of
      optic nerve damage is termed ocular hypertension, a risk factor for glaucoma that
      has been estimated to affect as many as 10% of individuals 40 years of age or
      older. OBJECTIVE: The purpose of this research was to assess persistency (time on
      therapy) with prostaglandin analogues in the treatment of glaucoma or ocular
      hypertension. METHODS: This population-based, retrospective cohort study used the
      Protocare Sciences managed care database, which includes prescription and medical
      claims data from multiple managed care organizations. Patients 20 years of age or
      older who initiated therapy with latanoprost, bimatoprost, or travoprost (index
      drugs) between April 2001 and June 2002 were included. Patients were required to
      be continuously enrolled in the same plan for the 180 days preceding index
      prescription fill. Follow-up continued through June 30, 2002. Two outcome
      measures were analyzed: (1) discontinuation of the index prostaglandin and (2)
      either discontinuation or change in the index prostaglandin regimen. Changing
      therapy was defined as switching to or adding another ocular hypotensive agent.
      Cox regression models were used to compare rate ratios of discontinuation and
      discontinuation/change. Patient data were censored on termination of insurance
      coverage or at the end of the study period. RESULTS: Overall, 7527 patients were
      prescribed a prostaglandin analogue; 4356 patients met the inclusion criteria (n
      = 2376, 993, and 987 for latanoprost, bimatoprost, and travoprost, respectively).
      A total of 58% of patients were women, and 74% were 65 years of age or older.
      Compared with latanoprost, those treated with bimatoprost were 38% more likely to
      discontinue and 31% more likely to discontinue/change therapy, and patients
      treated with travoprost were 36% more likely to discontinue and 29% more likely
      to discontinue/change therapy (P < 0.001 for each comparison). CONCLUSION:
      Latanoprost-treated patients demonstrated significantly (P < 0.001) greater
      persistency than did those treated with either bimatoprost or travoprost.

PMID- 12809965
TI  - An analysis of cholesterol control and statin use in the Losartan Intervention
      for Endpoint Reduction in Hypertension Study.
AB  - BACKGROUND: There is general agreement that patients who have elevated lipid
      levels and/or risk factors for or existing cardiovascular disease should receive
      aggressive cholesterol-lowering therapy. However, it is not clear whether
      patients are receiving the recommended treatment. OBJECTIVE: This study evaluated
      cholesterol control and statin use in the setting of a large, long-term
      cardiovascular end point trial. METHODS: The Losartan Intervention For Endpoint
      reduction in hypertension (LIFE) study was conducted between 1995 and 2001 to
      compare the incidence of cardiovascular morbidity and mortality with losartan- or
      atenolol-based treatment in 9193 patients aged 55 to 80 years with hypertension
      and left ventricular hypertrophy. The mean (SD) duration of follow-up was 4.8
      (0.9) years. Use of lipid-lowering therapy was at the discretion of the
      investigator. In the present study, analyses of baseline and end-of-study mean
      total cholesterol (TC) and high-density lipoprotein cholesterol levels and statin
      use were performed for the combined treatment groups. Based on generally accepted
      guidelines, achievement of a TC level <5.0 mmol/L (193.5 mg/dL) was used as the
      treatment target for the purpose of these analyses. The proportions of patients
      with TC levels above this cutoff were calculated at baseline and at the final
      visit. RESULTS: A total of 8653 patients had baseline and end-of-study
      cholesterol measurements and were included in this analysis. At baseline, 528
      (6.1%) patients were receiving statins; TC levels were above the cutoff in 381
      (72.2%) of these patients, who had a mean TC level of 6.07 mmol/L (234.7 mg/dL).
      Of 8125 (93.9%) patients who were not receiving statins at baseline, TC levels
      were above the cutoff in 6859 (84.4%), with a mean TC level of 6.37 mmol/L (246.4
      mg/dL). At the end of the study, 1892 (21.9%) patients were receiving a statin;
      TC levels were above the cutoff in 1096 (57.9%) of these patients, who had a mean
      TC level of 5.99 mmol/: (231.6 mg/dL). Of 6761 (78.1%) patients who were not
      receiving statins at the end of the study, TC levels were above the cutoff in
      5316 (78.6%), with a mean TC level of 6.24 mmol/L (241.4 mg/dL). CONCLUSIONS: In
      this long-term cardiovascular end point study in patients with moderate to severe
      hypertension and left ventricular hypertrophy, statins were not optimally
      administered and cholesterol levels were poorly controlled.

PMID- 12809966
TI  - An evaluation of the potential for pharmacokinetic interaction between
      escitalopram and the cytochrome P450 3A4 inhibitor ritonavir.
AB  - BACKGROUND: Depression often coexists with a number of disease states, and
      patients with a diagnosis of depression often receive multiple medications. Thus,
      it is desirable to avoid coadministration of agents that have a potential for
      drug interactions in these patients. Although escitalopram and its metabolites
      are weak to negligible inhibitors of the cytochrome P450 (CYP) 3A4 isozyme and
      are therefore unlikely to affect plasma concentrations of ritonavir (a CYP3A4
      substrate and prototype CYP3A4 inhibitor), ritonavir may potentially affect
      plasma concentrations of escitalopram, as CYP3A4 is partially responsible for
      conversion of escitalopram to its major metabolite, S-demethylcitalopram (S-DCT).
      OBJECTIVES: The aim of this study was to investigate the potential for
      pharmacokinetic interaction between escitalopram and ritonavir after concomitant
      administration of a single dose of each in healthy young subjects. METHODS: In
      this single-center, randomized, open-label, 3-way crossover study, subjects
      received each of the following: a single dose of escitalopram 20 mg, a single
      dose of ritonavir 600 mg, and single doses of both escitalopram 20 mg and
      ritonavir 600 mg. Blood was collected and plasma was analyzed for the
      pharmacokinetic parameters (maximum plasma concentration [C(max)], time to C(max)
      [T(max)], area under the plasma concentration-time curve, plasma elimination half
      life, oral clearance, and apparent volume of distribution) of escitalopram, S
      DCT, and ritonavir. RESULTS: Of 21 subjects (11 men, 10 women; mean [SD] age,
      28.4 [4.4] years) who were enrolled, 18 completed the study. After concomitant
      administration of escitalopram and ritonavir, no statistically significant
      differences were noted in the pharmacokinetics of escitalopram, with the
      exception of apparent volume of distribution, which was reduced by approximately
      10% (P < 0.001). The pharmacokinetics of S-DCT were unaffected by
      coadministration of ritonavir, with the exception of T(max), which was increased
      in the presence of ritonavir. The pharmacokinetic parameters of ritonavir were
      also unaffected by coadministration of escitalopram. CONCLUSION: In general, no
      pharmacokinetic interaction was observed between escitalopram and ritonavir in
      the present study.

PMID- 12809967
TI  - Targeted etanercept for discogenic neck pain: uncontrolled, open-label results in
      two adults.
AB  - BACKGROUND: Etanercept, a recombinant biologic anti-tumor necrosis factor (TNF)
      alpha therapeutic, is approved for the treatment of certain autoimmune
      arthritides by subcutaneous (SC) injection. TNF-alpha has been suggested to play
      a central role in neuropathic pain and neuronal damage associated with
      intervertebral disc herniation. Directed local administration of etanercept, in
      anatomic proximity to the site of disc and neuronal abnormality, may result in an
      enhanced therapeutic response. OBJECTIVE: This study reviews findings from 2
      patients with chronic, severe, discogenic cervical pain who were treated with a
      targeted cervical injection of etanercept with the objective of obtaining relief
      from their treatment-resistant pain. METHODS: In this uncontrolled, open-label
      study, the case histories of 2 patients (1 woman and 1 man) presenting with a
      history of chronic neck pain refractory to various treatments are reviewed. Both
      patients were treated with etanercept 25 mg by SC injection to the cervical
      region (case 1) or the posterior neck overlying the spine (case 2). RESULTS: Both
      patients experienced almost complete pain relief as assessed subjectively. In
      case 1, the Oswestry score decreased from 58 before treatment to 6 one day
      following treatment. In addition, 1 day after treatment the patient reported a
      subjective assessment of 98% pain improvement, 100% sensory improvement, and 100%
      weakness improvement. She has remained asymptomatic for >1 year. In case 2, the
      Oswestry score decreased from 44 before treatment to 4 two months after
      treatment. The patient reported 100% pain relief and 90% sensory improvement 1
      day after treatment. At 8-month follow-up, pain improvement continued to be 100%
      and sensory improvements was 75%. CONCLUSIONS: Etanercept, delivered by targeted
      SC injection, may be of benefit for selected patients with resistant pain
      associated with cervical disc disease. Further study of this new treatment
      modality is warranted.

PMID- 12809968
TI  - Assessment of the stability of dalteparin sodium in prepared syringes for up to
      thirty days: an in vitro study.
AB  - BACKGROUND: If a low-molecular-weight heparin (LMWH) injectable formulation
      maintains its stability for up to 30 days, substantial cost reductions in
      hospital stay could be achieved with its use on an outpatient basis in patients
      who might otherwise be treated with IV heparin as inpatients. OBJECTIVE: This
      study was designed to assess the stability for up to 30 days of injectable
      solutions of the LMWH dalteparin sodium when repackaged in plastic syringes.
      METHODS: In the first part of the study, 1-mL and 3-mL plastic syringes were
      filled with the contents of a 10,000-IU/mL dalteparin ampule or a 25,000-IU/mL
      dalteparin multidose vial. In a separate part of the study, 1-mL and 3-mL
      syringes were filled with doses of 7500 IU and 10,000 IU, respectively, from a
      10,000-IU/mL multidose vial. After the syringes were brought to room temperature
      or 4 degrees C, the stability of dalteparin was assessed over 30 days by
      measuring anti-factor Xa levels. RESULTS: No significant loss of dalteparin
      activity was found for up to 30 days in the syringes after storage at room
      temperature or 4 degrees C. The solutions retained anti-factor Xa activity at
      room temperature and under refrigeration. CONCLUSION: Dalteparin is stable for up
      to 30 days when stored at room temperature or 4 degrees C. The findings suggest
      that preparation of a postdischarge supply of dalteparin is feasible,
      contributing to more convenient and effective management of outpatients at risk
      for thrombotic complications.

PMID- 12809969
TI  - The complexity of assessing outcomes of combination therapy.

PMID- 12809970
TI  - Timeliness of review and approval of new drugs in Canada from 1999 through 2001:
      is progress being made?
AB  - BACKGROUND: The median time to approval of new drugs in Canada decreased
      considerably in the mid-1990s, although it continued to be longer than in such
      countries as Australia, Sweden, the United Kingdom, and the United States.
      Ongoing concern about approval times pointed to a need for a further
      international comparison. OBJECTIVE: This study was designed to assess whether
      there have been continuing improvements in drug approval times in Canada relative
      to these other countries. METHODS: Application and approval dates of new chemical
      or biological substances approved for marketing from 1999 through 2001 were
      requested from the Canadian, Australian, and Swedish regulatory agencies.
      Information for the United States was derived from publications of the
      Pharmaceutical Research and Manufacturers of America. The regulatory agency for
      the United Kingdom does not release application dates, although these were the
      same as the Swedish application dates for most drugs approved in both countries
      through the centralized European Union (EU) review procedure. Application dates
      for drugs licensed under the EU mutual-recognition arrangement or in the United
      Kingdom only were requested from the relevant pharmaceutical companies. RESULTS:
      One hundred eighty-six new drugs were approved in >/=1 of the countries studied
      between January 1999 and December 2001: 17 (9.1%) in all 5 countries, 25 (13.4%)
      in 4, 27 (14.5%) in 3, 39 (21.0%) in 2, and 78 (41.9%) in 1. Approval times were
      longer in Canada than in Australia, although not significantly so (median time,
      645 and 551 days, respectively). Canadian and Australian approval times were
      significantly longer than those in Sweden (431 days), the United Kingdom (479
      days), and the United States (371 days) (P < 0.001). The annual median approval
      time in Canada increased in each of the 3 years. The approval times of priority
      reviewed drugs in Canada were significantly longer than in the United States
      (median 317 vs 232 days) but significantly shorter than in Australia (509 days)
      (both comparisons, P < 0.001). CONCLUSIONS: Overall approval times of new drugs
      in Canada were longer than those in Australia, Sweden, the United Kingdom, and
      the United States in the period studied. The findings warrant ongoing monitoring
      of Canadian drug approval times.

PMID- 12809971
TI  - Assessment of the effect of ramipril therapy on direct health care costs for
      first and recurrent strokes in high-risk cardiovascular patients using data from
      the Heart Outcomes Prevention Evaluation (HOPE) study.
AB  - BACKGROUND: In the Heart Outcomes Prevention Evaluation (HOPE) Study, the
      angiotensin-converting enzyme (ACE) inhibitor ramipril was shown to significantly
      reduce the relative risk of stroke by 32% in high-risk cardiovascular patients (P
      < 0.001). However, the study did not examine the economic implications of these
      findings. OBJECTIVE: The purpose of this economic analysis was to estimate the
      potential economic benefits of the differences in direct health care costs
      attributable to the prevention of first and recurrent strokes in the HOPE Study
      patient population through the use of ramipril. METHODS: The epidemiologic
      component of the model examined the incidence of first and recurrent strokes in
      the HOPE Study population, assessed at annual increments, for the years 1995
      through 1997. An economic decision model was constructed by the application of
      costs to the epidemiologic foundation. Direct costs for stroke hospitalization
      and follow-up were calculated based on estimates provided by Samsa et al (1999).
      The estimated cost of ramipril treatment was based on the average wholesale price
      for the corresponding year of the analysis. The Samsa index costs are given in
      1991 US $; they were converted to study-year US $ using the Consumer Price Index
      for the corresponding year. RESULTS: The mean age of the patient population was
      69 years, with >70% of patients aged >/=65 years. When ACE-inhibitor treatment
      costs were included in the calculation of treatment costs, the expense to avert 1
      stroke was estimated at $13,766 for years 1 to 2 after randomization and $12,281
      for years 2 to 3. By years 3 to 4, ramipril treatment resulted in 21 fewer
      strokes and produced an estimated savings of $52,861. CONCLUSION: Ramipril 10
      mg/d was a cost-effective means of preventing first and recurrent ischemic
      strokes in the HOPE Study patient population.

PMID- 12809972
TI  - A time-series analysis of the effect of increased copayments on the prescription
      of antidepressants, anxiolytics, and sedatives in Sweden from 1990 to 1999.
AB  - BACKGROUND: Outpatient prescription medication spending in Sweden has increased
      sharply since 1974. The Swedish government has raised copayments to reduce
      medication consumption and limit the growth of medication spending. OBJECTIVE:
      The aim of this study was to examine the effect of the 1995 and 1997 copayment
      increases on Swedish consumption of antidepressants, anxiolytics, sedatives.
      METHODS: Monthly drug-use data for July 1990 through December 1999 for these 3
      pharmaceutical classes were obtained from Apoteket AB (Stockholm, Sweden). Data
      were provided for both sexes in units of defined daily doses per 1000
      inhabitants. These series were analyzed with the use of Box-Jenkins
      autoregressive, integrated, moving-average time-series modeling methods. RESULTS:
      Dispensing of all 3 drugs classes increased immediately before copayment changes,
      with the exception of male sedative use at the time of the 1997 reform. Permanent
      increases in male antidepressant and sedative use occurred before the 1995
      copayment reform. Only female antidepressant use was permanently reduced
      following the 1997 copayment reform. CONCLUSIONS: Our findings suggest that
      Swedish patients' valuation of mental health medications exceeds the enacted
      price increases. The permanent increases in male antidepressant and sedative use,
      beginning in 1995, may have been the result of previous undertreatment. The
      permanent reduction in female antidepressant use, beginning in 1997, suggests
      that the price levels reached a threshold that matched or exceeded Swedish
      women's valuation of these modific

PMID- 12809973
TI  - An economic assessment of the extent of medication use and wastage among families
      in Saudi Arabia and Arabian Gulf countries.
AB  - BACKGROUND: Expenditures for prescription and over-the-counter medications
      constitute a large percentage of total health care costs. Governments, health
      care providers, and consumers must work together to find ways to control these
      costs while continuing to provide quality health care for their nations. To this
      end, medication wastage is an unnecessary burden on an already fiscally
      restrained health care system. OBJECTIVE: This study was conducted to identify
      the extent of medication use and wastage among families in the Arabian Gulf
      countries, with an emphasis on Saudi Arabia. METHODS: A questionnaire was
      developed and administered to households in 5 regions in Saudi Arabia and other
      Gulf countries. A total of 1641 households participated in the study (1554 in
      Saudi Arabia; 87 in other countries). RESULTS: The mean (SD) family size of
      household respondents from Saudi Arabia was 6.60 (3.20) members, with 0.32%
      reporting no medicines present in the household, 81.8% of households reporting 5
      or more medicines, and 29.9% of respondents reporting having at least 10
      medications at home. Overall, the mean (SD) number of medicines per household in
      Saudi Arabia was 8.0 (4.3). The most common therapeutic classes of medications
      kept at home in Saudi Arabia were respiratory medications (16.8%), central
      nervous system agents (16.4%), and antibiotics (14.3%). The mean (SD) number of
      drug products unused, deteriorated, or expired was 2.2 (2.7) and 2.7 (1.9) per
      household in Saudi Arabia and other Gulf countries, respectively. From these
      data, mean medication wastage was estimated to be 25.8% (Saudi Arabia) and 41.3%
      (other Gulf countries). When analyzed on the basis of total medication cost,
      medication wastage was 19.2% and 25.0% in Saudi Arabia and other Gulf countries,
      respectively. The mean out-of-pocket expenditure (based on the percentage of
      annual income) for medications was 0.72% for households in Saudi Arabia compared
      with 0.48% in other Gulf countries. CONCLUSIONS: Families in Saudi Arabia and
      other Gulf countries spent a total of approximately US $150 million on
      medications that were never consumed. However, there appear to be no immediate
      solutions to the problem of medication wastage's impact on health care costs. The
      use of generic alternatives should be promoted, and drug use assessments should
      be implemented on a national level.

PMID- 12809974
TI  - In vivo micro magnetic resonance imaging signal changes in scrapie infected mice.
AB  - Signal abnormalities on magnetic resonance imaging (MRI) T2-weighted images
      (T2WI) have been described in patients with Creutzfeldt-Jakob disease; however,
      the pathology underlying these findings remains to be fully described. We
      investigated the time-course of signal alterations in a murine model of prion
      disease using in vivo 9.4 Tesla micro magnetic resonance imaging (muMRI). The
      topography of muMRI signal changes was correlated with the accumulation of
      proteinase resistant PrP(Sc) in corresponding brain sections. Increased signal
      intensity on T2WI was observed in the septum and in the hippocampus of
      presymptomatic mice 120 days post infection (dpi). Mildly symptomatic animals
      (150 dpi) and animals with apparent neurological deficit (180 dpi) had a greater
      increase of signal intensity on T2WI in the septum and the hippocampus; in
      addition, abnormalities in the cortex and in the thalamus were found.
      Neuropathological evaluation demonstrated accumulation of PrP(Sc) and
      astrogliosis but only minimal or no spongiform changes in structures where
      abnormal signal was detected. These observations suggest that early pathological
      changes related to the accumulation of PrP(Sc) may be detectable in
      presymptomatic subjects using MRI systems with higher magnetic field strength.

PMID- 12809975
TI  - Dioxin exposure down-regulates nitric oxide synthase and NADPH-diaphorase
      activities in the hypothalamus of Long-Evans rat.
AB  - In this study, we investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) gastric administration on the expression of neuronal nitric oxide synthase
      (nNOS) and the NADPH-diaphorase (NADPH-d) activities in the brain of the Long
      Evans rat. A single dose of TCDD (dissolved in olive oil, 50 microg/kg) or olive
      oil alone was administered to the rats by gavage. nNOS Western blotting
      experiment indicated a marked decrease in nNOS immunoreactivity at 1 and 2 weeks
      after TCDD treatment. NADPH-d histochemistry results showed a marked decrease in
      the number of NADPH-d stained cell bodies in the paraventricular hypothalamic
      nucleus, lateral hypothalamic area and perifornical nucleus in the TCDD-treated
      rats. The present study suggests that TCDD administration down-regulates nitric
      oxide product in the hypothalamus, which may be partially responsible for TCDD
      induced feeding inhibition.

PMID- 12809976
TI  - Expression patterns of inwardly rectifying potassium channel subunits in rat
      retina.
AB  - The expression patterns of inwardly rectifying potassium (Kir) channel subunits
      (Kir 1.1, 2.1, 2.3, 3.1, 3.2, 3.3, 4.1, and 4.2) were studied in rat retina by
      immunohistochemistry, with special emphasis on neuronal expression. Except for
      Kir4.1, the subunits tested were all expressed on neurons in the inner nuclear
      and ganglion cell layers. While Kir2.1 was densely present in the cytoplasm, the
      staining for all other subunits was predominantly expressed on the cell membrane.
      Most subunits, but not Kir 2.1 and 2.3, were present in the outer and inner
      plexiform layers to different extents. Kir4.1-immunoreactivity was found in
      astrocytes wrapping retinal blood vessels, in addition to the Muller cell
      endfoot. The differential expression of the Kir subunits suggests the diversity
      of physiological roles these channels may play.

PMID- 12809977
TI  - Removal of the superior cervical ganglia fails to block Fos induction in the
      accessory olfactory system of male mice after exposure to female odors.
AB  - When exposed to female odors, testosterone-primed male mice show a robust
      expression of immediate early genes in the vomeronasal organ (VNO) and associated
      accessory olfactory structures. We asked whether the superior cervical ganglia
      (SCG), which provide autonomic inputs to the VNO, are required for odor induction
      of Fos. Gonadally intact male mice received sham, unilateral, or bilateral SCG
      lesions and were exposed to odors from estrous females. In comparison to clean
      bedding, female odors significantly increased neuronal Fos immunoreactivity in
      sites throughout the VNO projection pathway, but these responses were not
      reliably modified by SCG removal. Thus, noradrenergic inputs to the VNO, which
      regulate a pumping mechanism thought to facilitate entrance of chemosignals into
      the VNO lumen, are not required for odors to induce Fos in the mouse accessory
      olfactory system.

PMID- 12809978
TI  - Cortical motor areas in plantar response: an event-related functional magnetic
      resonance imaging study in normal subjects.
AB  - The role of the cerebral cortices in normal plantar response was investigated
      with event-related functional magnetic resonance imaging (fMRI) at 3 Tesla in 12
      right-handed normal subjects. During fMRI acquisition, the lateral (LS) and
      medial (MS) side of the left sole was mechanically stimulated every 16 s to evoke
      the plantar response under monitoring of the surface electromyogram. LS activated
      the contralateral supplementary motor area (SMA) more intensively than MS. In
      contrast, no difference was found in the commonly activated areas including the
      contralateral primary sensorimotor area, bilateral secondary sensory areas and
      the thalamus. The results support the hypothesis that the normal plantar response
      is influenced by the cerebral cortices, and that the SMA likely participates in
      the regulation of the plantar reflex arc at the spinal level.

PMID- 12809979
TI  - Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease:
      evidence of effect modification by apolipoprotein E (APOE).
AB  - Insulin degrading enzyme (IDE) is a protease that degrades insulin and the beta
      amyloid peptide implicated in Alzheimer's disease (AD). We reexamined data on
      five previously reported IDE polymorphisms stratifying the analysis by the
      presence or absence of an apolipoprotein E (APOE) epsilon4 allele. Three IDE
      variants were associated with AD within epsilon4-negative subjects (genotype
      exact test P-values < or =0.02). A haplotype containing the minor variant at each
      of these sites represented an estimated 4.2% of case haplotypes versus 12.3% of
      control haplotypes among epsilon4-negative subjects. Lack of this minor haplotype
      may be predictive of AD, potentially explaining some fraction of disease within
      subjects without the APOE epsilon4 risk allele. Confirmation of this finding with
      a larger sample of cases and controls is warranted.

PMID- 12809980
TI  - Rate dependency of the human cortical network subserving executive functions
      during generation of random number series--a functional magnetic resonance
      imaging study.
AB  - In a random number generation (RNG) task subjects are instructed to generate the
      numbers 1-10 in a random fashion. RNG performance is assumed to involve executive
      functions, as it requires controlled response generation and suppression of
      habitual responses. To investigate cerebral structures involved in RNG associated
      executive functions we investigated functional magnetic resonance imaging in
      eight healthy subjects while performing an RNG task at two different response
      rates (1 and 2 Hz). During the 1 Hz condition an activation was detected
      bilaterally in the dorsolateral prefrontal cortex (BA 9/46), the lateral premotor
      cortex (BA 6), the anterior cingulate (BA 32), the inferior and superior parietal
      cortex (BA 7/40) and the cerebellar hemispheres. In the 2 Hz condition
      behavioural data showed higher counting tendencies reflecting poorer executive
      control. In parallel, a homogenous diminution of the activity in the involved
      cortical areas was obtained. This finding would support the theory of a cortical
      network involved in executive functions consisting of distinct brain regions
      working together rather than a distinct fronto-cortical functional localisation.

PMID- 12809981
TI  - Early gene expression in the rat cortex after experimental traumatic brain injury
      and hypotension.
AB  - To determine c-fos and egr-1 mRNA levels in the rat cortex after traumatic brain
      injury (TBI) and TBI plus hemorrhagic hypotension (HH). Sprague-Dawley rats were
      subjected to TBI. HH was induced by removing 5 ml of blood from the jugular vein
      for a duration of 20 min. Cortical tissue was harvested at 0 and 120 min, and
      mRNA levels of the immediate early genes c-fos, egr-1 were obtained. Rats that
      sustained TBI alone had increased c-fos and egr-1 mRNA expression at 120 min that
      was significant. Additionally, c-fos mRNA levels after TBI alone were
      significantly higher than c-fos mRNA levels after TBI+HH at 120 min. Levels of
      egr-1 mRNA after TBI alone at 120 min were not significantly higher than egr-1
      mRNA levels after TBI+HH at 120 min.

PMID- 12809982
TI  - Neurotrophin-like immunoreactivity in the gut of teleost species.
AB  - By means of immunochemistry and immunohistochemistry, we investigated in the gut
      of teleostean species the presence and localization of three neurotrophins: nerve
      growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin
      (NT)-3. In all studied species both NGF- and NT-3-like immunoreactivity (IR) were
      present in the enteric nervous system, while BDNF-like IR was never detected.
      More in particular, both NGF and NT-3-like IR were detected in neurons of small
      and large intestine, while only NT3-like IR was also observed in stomach
      plexuses. Furthermore, Western blot analysis revealed the presence of molecules
      immunoreactive to NGF and NT-3, which weight were very similar to those of
      mammalian corresponding neurotrophins. These results extend to teleost species
      the presence and distribution of NGF- and NT-3-like IR in the enteric nervous
      system, suggesting a well-preserved presence of these substances in the gut
      during vertebrate phylogenesis.

PMID- 12809983
TI  - Postnatal changes in nerve growth factor and brain derived neurotrophic factor
      levels in the retina, visual cortex, and geniculate nucleus in rats with
      retinitis pigmentosa.
AB  - Royal College of Surgeons (RCS) rats are a well established animal model of
      inherited retinitis pigmentosa (RP). Using RCS rats we examined the distribution
      of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in the
      visual cortex, geniculate nucleus and retina at three different postnatal ages.
      It was found that the retina of rats with RP expresses low amounts of NGF and
      BDNF in young and adult life. Altered levels of these factors were found in the
      visual cortex and in the geniculate nucleus. Our findings indicate that NGF and
      BDNF are differentially affected in the visual system of developing and adult RCS
      rats, suggesting that neurotrophins may be implicated in the pathogenesis of
      inherited RP.

PMID- 12809984
TI  - Inhibition of the human soleus Hoffman reflex during standing without descending
      commands.
AB  - The purpose of the present study was to ascertain the contribution of peripheral
      sensory inputs to posture-related Hoffman reflex (H-reflex) modulation in the
      human soleus muscle. The soleus H-reflexes were elicited in the sitting (SI) and
      passive standing (ST) conditions in patients with clinically complete spinal cord
      injuries (SCI) and in neurologically normal subjects. The results clearly showed
      suppression of the H-reflex amplitude during the ST compared with the SI
      condition especially in the SCI group. Considering the lack of a descending
      neural command in the SCI patients, our findings suggest that peripheral sensory
      inputs primarily contribute to the reduction of the soleus H-reflex during the
      upright standing posture.

PMID- 12809985
TI  - Spinal inhibitory synaptic transmission in the glycine receptor mouse mutant
      spastic.
AB  - Inhibitory glycine receptor (GlyR) and GABA(A) receptor (GABA(A)R)-mediated
      synaptic transmission was examined in two strains of the GlyR mutant mouse
      spastic and the respective wild types. The mutants display a mild and a severe
      neurological phenotype. Electrically evoked postsynaptic whole-cell currents were
      recorded from alpha-motoneurons in lumbar spinal cord slices. Amplitudes of GlyR
      mediated IPSCs were significantly reduced in the severe phenotype in comparison
      to the respective wild type and the mild phenotype mutants. Surprisingly,
      amplitudes of GABA(A)R-mediated IPSCs were also significantly reduced in both
      mutants. Fast time constants of the decay phase of IPSCs were slightly reduced
      for the GlyR-mediated IPSCs and significantly larger for the GABA(A)R-mediated
      IPSCs in both mutant strains.

PMID- 12809986
TI  - Unimodal circadian rhythm in the suprachiasmatic nucleus of behaviorally
      splitting mice.
AB  - CS mice exhibit rhythm splitting in constant darkness (DD). To examine the
      anatomical and physiological bases of this phenomenon, mouse Period1 (mPer1)
      driven green fluorescent protein (GFP) mice with rhythm splitting were produced
      by crossing CS and mPer1::GFP mice. GFP expression in the suprachiasmatic nucleus
      (SCN) slices showed a clear unimodal rhythm with the highest level at circadian
      time (CT) 8 or CT12 in splitting and non-splitting GFP mice under DD and no
      essential differences in the pattern of GFP expression were found between these
      mice. Moreover, there were no significant differences in the degree of symmetry
      in the paired rostral, central and caudal SCN between splitting and non-splitting
      mice. These results indicate that behavioral rhythm splitting in CS mice does not
      reflect the pattern of clock gene expression in the SCN.

PMID- 12809987
TI  - Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder
      pedigrees in humans.
AB  - Hypofunction of glutamatergic neurotransmission has been hypothesized to underlie
      the pathophysiology of bipolar affective disorder, as well as schizophrenia. We
      examined the role of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene
      on 16p13.3, a region thought to be linked to bipolar disorder, (1) because in a
      prior study we identified a functional and polymorphic (GT)n repeat in the 5'
      regulatory region of the gene, with longer alleles showing lower transcriptional
      activity and an over representation in schizophrenia, and (2) because of the
      suggestion of a genetic overlap between affective disorder and schizophrenia.
      Family-based association tests detected a nominally significant preferential
      transmission of longer alleles in a panel of 96 multiplex bipolar pedigrees.
      These results support the hypothesis that a hypoglutamatergic state is involved
      in the pathogenesis of bipolar affective disorder.

PMID- 12809988
TI  - Increase of preprotachykinin mRNA in the uninjured mandibular neurons after rat
      infraorbital nerve transection.
AB  - An increasing number of studies are suggesting that the adjacent uninjured
      primary afferents contribute to the mechanisms of neuropathic pain following
      peripheral nerve injury. In this study, we report that transection of the
      infraorbital nerve, a major branch of the maxillary nerve, causes exaggerated
      face grooming to normally innocuous mechanical stimuli in the skin territory of
      the uninjured mandibular nerve, and increases the expression of preprotachykinin
      mRNA in the primary afferent neurons in the mandibular zone in the trigeminal
      ganglia. Considering the various functions of substance P in the sensory
      transmission process, the increase in preprotachykinin mRNA in the uninjured
      primary afferent neurons may be one of the mechanisms of pain-related behavior in
      this neuropathic pain model.

PMID- 12809989
TI  - Signal transducer and activator of transcription-3 activation is mediated by N
      methyl-D-aspartate receptor and L-type voltage-gated Ca2+ channel during cerebral
      ischemia in rat hippocampus.
AB  - It has been proved that signal transducer and activator of transcription-3
      (STAT3) is expressed and activated following cerebral ischemia/reperfusion in
      cortex and striatum. Here we investigated the changes in tyrosine phosphorylation
      and DNA-binding activity of STAT3 in hippocampus in a four-vessel occlusion model
      of Sprague-Dawley rats. Phospho-STAT3 (in cytoplasm) was enhanced from 5 min and
      reached its peak level at 10 min of ischemia. While in nucleus, phospho-STAT3
      increased from 10 min and then peaked at 30 min of ischemia. Concomitantly, DNA
      binding activity of STAT3 demonstrated a similar rule in nucleus extracts. The
      increased tyrosine phosphorylation and DNA-binding activity of STAT3 in nucleus
      were blocked by ketamine, an N-methyl-D-aspartate receptor antagonist, or by
      nifedipine, a L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist. These
      results illustrated that the ionotropic glutamate receptor and L-VGCC are
      important in mediating STAT3 activation during severe cerebral ischemia.

PMID- 12809990
TI  - Perturbations in the thiol homeostasis following neonatal cerebral hypoxia
      ischemia in rats.
AB  - Changes in the thiol/disulphide status in the neonatal rat brain were evaluated
      after an episode of neonatal hypoxia-ischemia (HI) in 7-day-old rats. The
      glutathione level decreased in the post-HI period. The lowest values (43-68%)
      were obtained 24 h post-HI. A statistically significant difference first appeared
      in hippocampus, immediately after the HI event, and only 12 h later in striatum
      and cortex. On the 7th day post-HI the glutathione content was completely
      recovered in the hippocampus and the striatum, and partially in the cortex. The
      glutathione loss could not be explained through its conversion to glutathione
      disulphide or to protein mixed disulphide (S-thiolation), whose values remained
      constant. Furthermore, we found a consistent decrease (20-30%) in protein thiols,
      which were not recovered after 7 days post-HI. Perturbations in protein thiols,
      along with the glutathione loss, may represent a valuable marker of immature rat
      brain damage.

PMID- 12809991
TI  - Compatibility of bidirectional synaptic plasticity on hippocampo-prefrontal
      cortex pathway in rats.
AB  - The hippocampo-prefrontal cortex pathway reportedly expresses long-term
      potentiation (LTP) and depression (LTD) in anesthetized rats. We examined whether
      there were any effects governing the induction of LTD after prior induction of
      LTP, or vice versa. Induction in sequence of LTP and LTD resulted in
      significantly stable changes of about 140 and 70% of a common control for 1 h
      each. The reversed sequence, LTD and LTP, showed a mirror image of about 65 and
      135% of control, which were not different from the respective changes in the
      first sequence (P>0.3 for each). The correlation coefficient between changes was
      significantly positive in the first sequence and weakly negative in the reverse.
      These results indicate that this pathway can express compatibility of
      bidirectional synaptic plasticity while historical changes remain covert.

PMID- 12809992
TI  - The midlatency auditory evoked potential P50 is abnormal in Huntington's disease.
AB  - The P50 (or P1) potential is a midlatency auditory evoked response, believed to
      be partially generated by the cholinergic pedunculopontine nucleus (PPN) neurons
      that give rise to the ascending reticular activating system (RAS). We compared
      the P50 potential in 11 Huntington's disease (HD) patients and 13 normal controls
      using a paired click stimulus paradigm. HD patients exhibited a P50 potential
      with reduced amplitude and increased latency to the first stimulus of the pair
      (first P50 potential), suggesting impaired ascending reticular activating system
      function, which may contribute to sleep disorders seen in HD. Sensory gating,
      measured as the percent ratio of the second P50 potential amplitude to the first
      P50 potential amplitude, was reduced at 250 and 500 ms interstimulus intervals
      (ISI), which may be related to disordered attention and anxiety in HD.

PMID- 12809993
TI  - Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis
      and myelopathy.
AB  - After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic
      radicular sacral-distribution pain (zoster sine herpete), cervical-distribution
      zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella
      zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with
      reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for
      albumin and total IgG, proved that VZV caused the protracted neurological
      complications. Diagnosis by antibody testing led to aggressive antiviral
      treatment and a favorable outcome.

PMID- 12809994
TI  - Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple
      sclerosis patients presenting with severe myelitis.
AB  - Recent studies showed that the 14-3-3 protein is detectable in the cerebrospinal
      fluid (CSF) of prion-unrelated neurological diseases, such as meningoencephalitis
      and myelitis. To investigate the possible association between the amounts of the
      14-3-3 protein in the CSF and the clinical severity of multiple sclerosis (MS),
      its levels were determined by Western blot in the CSF of the patients with
      relapsing-remitting MS (RRMS) (n=10), secondary progressive MS (SPMS) (n=7),
      primary progressive MS (PPMS) (n=2), and non-MS inflammatory diseases of the CNS
      (n=5). The 14-3-3 protein was identified in seven CSF samples, including four
      patients with SPMS in acute relapse, one with SPMS in remission accompanied by
      fresh cerebral infarction, one with RRMS in acute relapse, and one with human T
      lymphotropic virus type I (HTLV-I)-associated myelopathy. The patients positive
      for the CSF 14-3-3 protein immunoreactivity showed more severe disability and
      higher levels of pleocytosis, protein, IgG, beta2-microglobulin, and neuron
      specific enolase in the CSF, compared with those negative for its
      immunoreactivity. Four of these patients exhibited extensive lesions distributed
      along multiple vertebral segments in the spinal cord on MRI. In contrast, none of
      the MS patients without an extensive involvement of the spinal cord showed the
      CSF 14-3-3 protein immunoreactivity. These results suggest that detection of the
      14-3-3 protein in the CSF provides a marker for severe inflammation-induced
      extensive damage of the central nervous system tissues responsible for poor
      therapeutic responses and irreversible neurological deficits in MS.

PMID- 12809995
TI  - 1H-NMR spectroscopy combined with pattern recognition analysis reveals
      characteristic chemical patterns in urines of MS patients and non-human primates
      with MS-like disease.
AB  - Proton nuclear magnetic resonance (1H-NMR) spectroscopy in combination with
      pattern recognition techniques were used to investigate the composition of
      organic compounds in urines from patients with multiple sclerosis (MS), patients
      with other neurological diseases (OND) and healthy controls (H). Using a valid
      animal model of MS, namely the common marmoset (Callithrix jacchus) model of
      experimental autoimmune encephalomyelitis (EAE), the relation of disease
      progression and alteration of the urine composition was investigated. Urine
      samples were collected during different stages of EAE, either induced with whole
      human myelin or with the myelin protein MOG in complete adjuvant. The urine
      samples were analysed with 1H-NMR spectroscopy allowing simultaneous detection of
      an array of compounds. Spectral differences between urines from EAE-affected and
      healthy monkeys were assessed with multivariate analysis. Evidence is provided
      that development of EAE is associated with changes in the chemical composition of
      the urine, in particular of compounds with NMR peaks in the region of the
      spectrum between 0.5 and 3.50 ppm. In addition, we found preliminary evidence for
      differences between urines from MS, OND and H groups.

PMID- 12809996
TI  - Video-assisted thoracoscopic extended thymectomy and extended transsternal
      thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after
      6 years of follow-up.
AB  - The aims of this study were to assess the efficacy of video-assisted
      thoracoscopic extended thymectomy (VATET) as a treatment for myasthenia gravis
      (MG) and to identify prognostic factors for thymectomy success. Clinical efficacy
      and variables influencing outcome were assessed by life-table and Cox
      proportional hazards regression analysis. Complete stable remission (CSR), as
      defined by the MGFA Medical Task Force, was the end point for efficacy. VATET was
      performed in 159 MG patients and T-3b in 47 MG patients. At 6 years of follow-up,
      CSR, assessed by life-table analysis, was 50.6% in non-thymomatous VATET patients
      and 48.7% in non-thymomatous T-3b surgery. By univariate analysis, the presence
      of thymic hyperplasia (P=0.0002) and treatment only with anticholinesterases
      (P<0.0001) were positively associated with the probability of CSR. By
      multivariate analysis, the chance of complete remission was significantly
      increased by the use of anticholinesterases (odds ratio [OR] 2.45; 95% confidence
      interval [CI] 1.44-4.17; P=0.001) and the presence of thymic hyperplasia (OR
      1.96; 95% CI 1.05-3.68; P=0.036). VATET seems to be effective in inducing CSR in
      MG with an efficiency similar to that of the T-3b transsternal (TS) approach; it
      is easy to perform in experienced hands and is associated with low morbidity and
      negligible esthetic sequelae.

PMID- 12809997
TI  - Early pregnancy factor treatment suppresses the inflammatory response and
      adhesion molecule expression in the spinal cord of SJL/J mice with experimental
      autoimmune encephalomyelitis and the delayed-type hypersensitivity reaction to
      trinitrochlorobenzene in normal BALB/c mice.
AB  - Early pregnancy factor (EPF) is a secreted protein, present in serum during early
      pregnancy and essential for maintaining viability of the embryo. It is a
      homologue of chaperonin 10 (Cpn10) but, unlike Cpn10, it has an extracellular
      role. EPF has immunosuppressive and growth regulatory properties. Previously we
      have reported the preparation of recombinant EPF (rEPF) and shown that treatment
      with rEPF will suppress clinical signs of MBP-EAE in Lewis rats and PLP-EAE in
      SJL/J mice. In the present study, these findings have been extended to
      investigate possible mechanisms involved in the action of EPF. Following
      treatment of mice with rEPF from the day of inoculation, there were fewer
      infiltrating CD3+ and CD4+ cells in the parenchyma of the spinal cord during the
      onset of disease and after the initial episode, compared with mice treated with
      vehicle. Expression of the integrins LFA-1, VLA-4 and Mac-1 and of members of the
      immunoglobulin superfamily of adhesion molecules ICAM-1 and VCAM-1 was suppressed
      in the central nervous system (CNS) following rEPF treatment. The expression of
      PECAM-1 was not affected. To determine if rEPF suppressed T cell activation in
      the periphery, the delayed-type hypersensitivity (DTH) reaction of normal BALB/c
      mice to trinitrochlorobenzene (TNCB) following treatment with rEPF was studied.
      The results showed that treatment with rEPF suppressed the DTH reaction,
      demonstrating the ability of EPF to downregulate the cell-mediated immune
      response. These results indicate that suppression of immunological mechanisms by
      rEPF plays a major role in the reduction of clinical signs of disease in
      experimental autoimmune encephalomyelitis (EAE).

PMID- 12809998
TI  - Gait dynamics in Parkinson's disease: relationship to Parkinsonian features,
      falls and response to levodopa.
AB  - OBJECTIVES: Patients with Parkinson's disease (PD) have an increased risk of
      falling that has yet to be fully explained. To better understand the gait
      disturbance in PD and the factors that contribute to falls, we quantitatively
      evaluated: (1) the relationship between gait variability (a marker of fall risk
      in other populations), fall history, and other parkinsonian features, and (2) the
      effects of levodopa on these relationships. METHODS: The average stride time and
      stride-to-stride variability were measured using force-sensitive insoles during
      comfortable walking. Fall frequency, motor control, function, and mental health
      were measured using the Unified Parkinson's Disease Rating Scale (UPDRS), the
      Mini-Mental State Exam (MMSE), and the timed motor tests of the Core Assessment
      Program for Intracerebral Transplantations (CAPIT) in 32 subjects with idiopathic
      PD, in an "off" (unmedicated) state and again in an "on" (medicated) state.
      RESULTS: Average stride time was not associated with any UPDRS or CAPIT measure
      and was similar in fallers and non-fallers in "off" and "on" states (p>0.27).
      Stride time variability was significantly associated with fall frequency as well
      as with total scores on the CAPIT and the UPDRS, ADL abilities, and motor
      function. Stride time variability and falls were not related to tremor, rigidity
      or bradykinesia in the "off" state. 41% of subjects reported one or more falls.
      Stride time variability was 8.8+/-7.9% in fallers and 4.2+/-1.3% in non-fallers
      (p<0.009). Stride time variability significantly improved in response to
      levodopa, both in fallers and non-fallers, but remained increased in fallers (vs.
      non-fallers). CONCLUSIONS: The patho-physiology responsible for impaired stride
      to-stride regulation of gait timing is apparently independent of other cardinal
      features of PD, i.e., tremor, rigidity, or bradykinesia, but is responsive to
      levodopa. Stride-to-stride variability is especially impaired among PD subjects
      with a history of falls, suggesting, for the first time, the possibility of
      exaggerated impairment of internal clock function in PD fallers.

PMID- 12809999
TI  - Coagulation-fibrinolysis abnormalities in patients receiving antiparkinsonian
      agents.
AB  - Neuroleptic malignant syndrome (NMS) is induced by alteration of medication in
      Parkinson's disease (PD); and blood coagulation disorder is regarded as one of
      the mechanisms implicated in NMS. We have studied markers of blood coagulation
      and fibrinolysis in 270 patients with PD and 159 healthy controls matched in age
      and gender. The average values of prothrombin time (international normalized
      ratio) and plasma levels of prothrombin fragment(1+2), D-dimer, plasmin-alpha 2
      antiplasmin complex, thrombomodulin and E-selectin were higher in patients
      receiving antiparkinsonian agents as compared to the patients without any
      medication or healthy controls. The effect of antiparkinsonian drugs was analyzed
      by dividing the patients into three groups according to the medication: the
      patients under the combination therapy with levodopa and a dopamine agonist, the
      patients administered levodopa, and those that received a dopamine agonist. Of
      the three groups, the patients under the combination therapy had the highest
      values of these markers, and those treated with only levodopa had the lowest
      values. PD patients receiving antiparkinsonian drugs are often associated with
      blood coagulation abnormalities, and plasma hemostatic markers should be
      routinely assessed in the management of such patients. Further study is needed to
      determine whether these abnormalities predispose to the development of NMS.

PMID- 12810000
TI  - Multi-unit activity suppression and sensorimotor deficits after endothelin-1
      induced middle cerebral artery occlusion in conscious rats.
AB  - Conscious Wistar rats with stereotaxically and unilaterally implanted cannula
      just above the middle cerebral artery (MCA) were injected with the powerful
      vasoconstrictor peptide endothelin-1 (ET1, 60 pmol in 3 microl). The purpose was
      to examine the long-term (from the 1st to the 14th day) changes in neuronal
      bioelectrical activity together with sensorimotor deficits after ET1-induced MCA
      occlusion (MCAO). Extracellular multi-unit activity (MUA) recorded from the
      ipsilateral fronto-parietal cortical area (supplied by MCA) and sensorimotor
      behavior (one postural reflex test and six limb placing tests) were examined. A
      significant suppression of the multi-unit activity was observed until the 14th
      day post-ET1. The rats exhibited significant unilateral sensorimotor deficits
      with a maximum at the 3-7 days after ET1 and a spontaneous partial recovery by
      days 11-14. A significant correlation was found between the suppression of the
      multi-unit activity and the sensorimotor deficits between the 3rd and the 10th
      day post-ET1. The results suggest that studying the bioelectrical activity in
      combination with the behavioral sensorimotor functions may be of use to assess
      the functional disturbances associated with focal cerebral ischemia and would
      help to examine the therapeutic benefits of various cerebroprotective treatments
      before initiating human clinical trials.

PMID- 12810001
TI  - Viliuisk encephalomyelitis: intrathecal synthesis of oligoclonal IgG.
AB  - Viliuisk encephalomyelitis (VE) is a neurodegenerative disorder expressed as
      subacute meningo-encephalitis progressing to a more prolonged pan-encephalitic
      syndrome with a fatal outcome within 1 to 10 years. Some patients survive to a
      steady state of global dementia and severe spasticity that may last for over 20
      years. Multiple micronecrotic foci surrounded by inflammatory infiltrates are
      observed throughout the cerebral cortex and other gray matter areas. Infectious
      etiology of VE is strongly suspected, but the causative agent has not been
      identified. We conducted a search for assays that might be helpful for VE
      diagnosis and established for the first time that the majority of patients with
      definite VE show evidence for intrathecal IgG synthesis correlating with the
      clinical manifestations of the disease. This indicates that the detection of
      oligoclonal IgG banding in the cerebrospinal fluid is a valuable diagnostic assay
      for VE. Implications of these findings for a possible etiology of VE are
      discussed.

PMID- 12810002
TI  - Identification of a novel KRIT1 mutation in an Italian family with cerebral
      cavernous malformation by the protein truncation test.
AB  - Familial cerebral cavernous malformation (CCM) exhibits autosomal dominant
      inheritance and is characterized by vascular disorders of the brain, which can
      lead to seizures, focal neurological deficits, hemorrhagic stroke, and migraine.
      Three CCM loci have been mapped, but the gene for only one locus--KRIT1 coding
      for Krev-1/rap1 interaction trapped 1 (KRIT1) protein, which is responsible for
      more than 40% of familial cases--has been identified. To date, a total of 72
      mutations have been described, with one founder effect in the Mexican/Hispanic
      community. We report the case of an Italian family with CCM that has a novel
      KRIT1 gene mutation leading to a truncated KRIT1 protein. The protein truncation
      test (PTT) has been used as a rapid method of identifying germline mutations in
      the KRIT1 gene.

PMID- 12810003
TI  - Genetic, clinical and pathological studies of CADASIL in Japan: a partial
      contribution of Notch3 mutations and implications of smooth muscle cell
      degeneration for the pathogenesis.
AB  - We have examined Notch3 mutations in patients with cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose
      samples were submitted to us in Japan. The subjects were composed of 21 Japanese,
      1 Iranian, 1 Korean and 1 Canadian families. Mutations in the Notch3 gene were
      found in 7 of 24 families examined. These were R133C in two unrelated Japanese
      families, and R213K, C174F and R169C in each Japanese family. In addition, we
      have found R90C in an Iranian family and C174R in a Korean family. Thus,
      contribution of Notch3 gene mutations is less than one fourth of Japanese CADASIL
      families, suggesting the existence of other causative genes in CADASIL. It is
      also of interest to know that Notch3 mutant CADASIL exists in other Asian
      countries. We next examined the localization of Notch3 protein in the tissue by
      immunohistochemistry. It was restricted to the wall of arterioles in the brain
      and other organs. In the brain, there was no difference in the staining pattern
      among arterioles in the cortex, white matter and meninges. The staining was
      negative in the venule and capillaries as well as in neurons and glial cells.
      From the staining pattern, it was recognized to be expressed in the vascular
      smooth muscle cells in the adult tissue. In an autopsy case with R213K mutation,
      we could see numerous cerebral infarcts and arteriole wall degeneration with
      deposits of granular osmiophilic material (GOM). However, it is interesting to
      note that occlusion of arterioles was rarely observed and the GOM was negative
      for Notch3 staining. These findings suggest that hemodynamic abnormalities due to
      smooth muscle cell degeneration may be important in the pathogenesis of CADASIL.

PMID- 12810004
TI  - Activation of a residual cortical network during painful stimulation in long-term
      postanoxic vegetative state: a 15O-H2O PET study.
AB  - Survivors of prolonged cerebral anoxia often remain in the persistent vegetative
      state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O
      PET to analyze their central processing of pain. The study was approved by the
      local Ethics Committee, the experiments were performed in accordance with the
      Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin
      for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed
      functional PET of the brain using 15O-labelled water during electrical
      nociceptive stimulation. Additionally, a brain metabolism study using 18F
      fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set)
      were acquired in all patients. PET data were analyzed by means of Statistical
      Parametric Mapping (SPM99) and coregistered to a study-specific brain template.
      MRI and FDG PET showed severe cortical impairment at the structural and the
      functional level, that is, general atrophy of various degrees and a widespread
      significant hypometabolism, respectively. Pain-induced activation
      (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex
      (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate
      cortex contralateral to the stimulus and in the posterior insula ipsilateral to
      the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex
      pain-processing matrix were significantly activated. In conclusion, the regional
      activity found at the cortical level indicates that a residual pain-related
      cerebral network remains active in long-term PVS patients.

PMID- 12810005
TI  - Diurnal locomotor activity and oxidative metabolism of the suprachiasmatic
      nucleus in two models of hepatic insufficiency.
AB  - Subjects with hepatic cirrhosis develop alterations of several rhythmic
      behavioural and biochemical patterns. Since most cirrhotic patients combine
      portal hypertension and hepatic impairment, our work aims to assess the extent to
      which rhythmical changes can be due to hepatic insufficiency or portal
      hypertension. This was done using two experimental models in rats, portacaval
      shunt model (PC) and portal hypertension by a triple stenosing ligature of the
      portal vein (PH). We assess diurnal locomotor activity and determine the
      oxidative metabolism of the suprachiasmatic nucleus (SCN) by histochemical
      determination of cytochrome oxidase (COX). The results show that animals with PC
      have altered diurnal locomotor rhythm compared to control and PH rats (p<0.001).
      They also present lower COX activity in the SCN (p<0.05). We conclude that
      rhythmic alterations are due to hepatic insufficiency and not to portal
      hypertension.

PMID- 12810006
TI  - Extensive bihemispheric ischemia caused by acute occlusion of three major
      arteries to the brain.
AB  - An 86-year-old woman developed cardioembolic stroke three times. In the last one,
      she fell into sudden coma and fatal outcome due to acute occlusion of bilateral
      internal carotid arteries (ICAs) and the basilar artery. Diffusion-weighted
      magnetic resonance imaging (MRI) delineated brain ischemia in the whole bilateral
      cerebral hemisphere soon after the stroke onset. Signal intensity of the brain
      parenchyma increased in whole the hemisphere. Especially, all the cortical rims
      glittered. This is the first report of the cardioembolic stroke due to
      simultaneous occlusion of the three major arteries to the brain.

PMID- 12810007
TI  - Nuclear spin relaxation in paramagnetic systems (S>/=1) under fast rotation
      conditions.
AB  - A new theoretical model for nuclear spin relaxation in paramagnetic systems in
      solution has been developed. Fast rotational motion is included in the model,
      both as a source of modulation of the static zero-field splitting, which provides
      a mechanism for electron spin relaxation, and as an origin of the stochastic
      variation of the electron spin-nuclear spin dipole-dipole interaction leading to
      nuclear spin relaxation. At the limit of low magnetic field, the model is
      essentially identical to the earlier formulations from our laboratory, but new
      closed-form expressions are given for the inner- and outer-sphere relaxation at
      the high-field limit. Numerical comparisons with a general theory are reported
      for the inner-sphere case. In addition, some nuclear magnetic relaxation
      dispersion (NMRD) profiles from the literature are considered for systems where
      experiments have been done with both low-molecular weight paramagnetic complexes
      and their adducts with proteins. Previously developed theories are used to
      interpret data for the slowly rotating protein adducts, and good fits of the fast
      rotating counterparts are obtained by further adjustment of one or two additional
      parameters.

PMID- 12810008
TI  - Laser-polarized 129Xe NMR at 1.88 T and 8.5 mT: a signal-to-noise ratio
      comparison.
AB  - The signal-to-noise ratio of nuclear magnetic resonance signals from laser
      polarized 129Xe gas was investigated at 8.5 mT and compared to that of signals
      acquired at 1.88 T. A dedicated 8.5 mT resistive magnet was constructed and used
      to acquire the signals. The SNR for 1 atm of xenon gas with a polarization of 1%
      was measured to be 1900 at a field of 1.88 T. Under identical acquisition
      conditions, the SNR at 8.5 mT was about 60 (or 32 times lower). After measuring
      and including all of the electrical factors of the detection systems at each
      field strength, theory indicates the SNR value measured at 8.5m T should be about
      36 times lower. Considering the widely differing frequencies and completely
      different detection systems the agreement is quite good and indicates that
      extrapolating the frequency dependence of the SNR down to very low fields does
      work as long as the detection system parameters are carefully accounted for. This
      work suggests that magnetic resonance (MR) imaging is achievable on ideal gas
      samples at 8.5 mT using laser-polarized 129Xe gas down to the practical
      resolution limit of about 0.5mm, although the SNR will be very low (approximately
      1.4). The feasibility of imaging small animals at 8.5 mT is discussed and it is
      suggested that a field of about 50 mT is required.

PMID- 12810009
TI  - An improved gridding method for spiral MRI using nonuniform fast Fourier
      transform.
AB  - The algorithm of Liu and Nguyen [IEEE Microw. Guided Wave Lett. 8 (1) (1998) 18;
      SIAM J. Sci. Comput. 21 (1) (1999) 283] for nonuniform fast Fourier transform
      (NUFFT) has been extended to two dimensions to reconstruct images using spiral
      MRI. The new gridding method, called LS_NUFFT, minimizes the reconstruction
      approximation error in the Least Square sense by generated convolution kernels
      that fit for the spiral k-space trajectories. For analytical comparison, the
      LS_NUFFT has been fitted into a consistent framework with the conventional
      gridding methods using Kaiser-Bessel gridding and a recently proposed generalized
      FFT (GFFT) approach. Experimental comparison was made by assessing the
      performance of the LS_NUFFT with that of the standard direct summation method and
      the Kaiser-Bessel gridding method, using both digital phantom data and in vivo
      experimental data. Because of the explicitly optimized convolution kernel in
      LS_NUFFT, reconstruction results showed that the LS_NUFFT yields smaller
      reconstruction approximation error than the Kaiser-Bessel gridding method, but
      with the same computation complexity.

PMID- 12810010
TI  - Automated data processing of [1H-decoupled] 13C MR spectra acquired from human
      brain in vivo.
AB  - In clinical 13C infusion studies, broadband excitation of 200 ppm of the human
      brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to
      2000 metabolite peaks over 2h. We describe a fast, automated, observer
      independent technique for processing [1H-decoupled] 13C spectra. Quantified 13C
      spectroscopic signals, before and after the administration of [1-13C]glucose
      and/or [1-13C]acetate in human subjects are determined. Stepwise improvements of
      data processing are illustrated by examples of normal and pathological results.
      Variation in analysis of individual 13C resonances ranged between 2 and 14%.
      Using this method it is possible to reliably identify subtle metabolic effects of
      brain disease including Alzheimer's disease and epilepsy.

PMID- 12810011
TI  - BlochLib: a fast NMR C++ tool kit.
AB  - Computational power, speed, and algorithmic complexity are increasing at a
      continuing rate. As a result, scientific simulations continue to investigate more
      and more complex systems. Nuclear magnetic resonance (NMR) is no exception. NMR
      theory and language is extremely well developed, that simulations have become a
      standard by which experiments are measured. Nowadays, complex computations can be
      performed on normal workstations and workstation clusters. Basic numerical
      operations have also become extremely optimized and new computer language
      paradigms have become implemented. Currently there exists no complete NMR tool
      kit which uses these newer techniques. This paper describes such a tool kit,
      BlochLib. BlochLib is designed to be the next generation of NMR simulation
      packages; however, the basic techniques implemented are applicable to almost any
      problem. BlochLib enables the user to simulate almost any NMR idea both
      experimental or theoretical in nature. Both classical and quantum mechanical
      techniques are included and demonstrated, as well as several powerful user
      interface tools. The total tool kit and documentation can be found at
      http://waugh.cchem.berkeley.edu/blochlib/.

PMID- 12810012
TI  - Ultra-broadband NMR probe: numerical and experimental study of transmission line
      NMR probe.
AB  - We have reinvestigated a transmission line NMR probe first published by Lowe and
      co-workers in 1970s [Rev. Sci. Instrum. 45 (1974) 631; 48 (1977) 268] numerically
      and experimentally. The probe is expected to be ultra-broadband, thus might
      enable new types of solid-state NMR experiments. The NMR probe consists of a coil
      and capacitors which are connected to the coil at regular intervals. The circuit
      is the same as a cascaded LC low-pass filter, except there are nonzero mutual
      inductances between different coil sections. We evaluated the mutual inductances
      by Neumann's formula and calculated the electrical characteristics of the probe
      as a function of a carrier frequency. We found that they were almost the same as
      those of a cascaded LC low-pass filter, when the inductance L of a section was
      estimated from the inductance of the whole coil divided by the number of the
      sections, and if C was set to the capacitance in a section. For example, the
      characteristic impedance of a transmission line coil is given by Z=(L/C)(1/2). We
      also calculated the magnitude and the distribution of RF magnetic field inside
      the probe. The magnitude of RF field decreases when the carrier frequency is
      increased because the phase delay between neighboring sections is proportional to
      the carrier frequency. For cylindrical coils, the RF field is proportional to
      (pinu/2nu(d))(1/2)exp(-nu/nu(d)), where the decay frequency nu(d) is determined
      by the dimensions of the coil. The observed carrier frequency thus must be much
      smaller than the decay frequency. This condition restricts the size of
      transmission line coils. We made a cylindrical coil for a 1H NMR probe operating
      below 400 MHz. It had a diameter 2.3mm and a pitch 1.2mm. Five capacitors of 6pF
      were connected at every three turns. The RF field strength was 40 and 60 kHz at
      the input RF power 100 W by a calculation and by experiments, respectively. The
      calculations showed that the RF field inhomogeneity along the coil axis was
      caused by a standing wave of current, which arose from the reflections at the
      coil ends. The calculation showed that the homogeneity could be improved by
      decreasing the pitch near the both ends and making their impedance close to that
      at the center.

PMID- 12810013
TI  - Two-dimensional Hadamard spectroscopy.
AB  - Direct frequency-domain excitation of NMR with an array of different
      radiofrequencies has been used to speed up two-dimensional NMR experiments by a
      large factor. Multiplex excitation in the F(1) frequency dimension is restricted
      to the signal-bearing regions and is encoded according to a Hadamard matrix of
      dimension N by N, where N is a relatively small number. The detected signals are
      decoded by reference to the same Hadamard matrix. Alternatively a phase-encoding
      scheme can be employed. Two-dimensional correlation experiments (COSY and TOCSY)
      and cross-relaxation measurements (NOESY) implemented on proton systems can be
      completed in less than a minute in cases where the intrinsic sensitivity is
      sufficiently high that prolonged multiscan averaging is not required. The results
      are presented in the form of a high-resolution contour diagram similar to the
      familiar two-dimensional spectra obtained by Fourier transform methods.
      Experiments on strychnine demonstrate more than two orders of magnitude
      improvement in speed compared with the traditional methods.

PMID- 12810014
TI  - Optimal control of spin dynamics in the presence of relaxation.
AB  - Experiments in coherent spectroscopy correspond to control of quantum mechanical
      ensembles guiding them from initial to final target states. The control inputs
      (pulse sequences) that accomplish these transformations should be designed to
      minimize the effects of relaxation and to optimize the sensitivity of the
      experiments. For example in nuclear magnetic resonance (NMR) spectroscopy, a
      question of fundamental importance is what is the maximum efficiency of coherence
      or polarization transfer between two spins in the presence of relaxation.
      Furthermore, what is the optimal pulse sequence which achieves this efficiency?
      In this paper, we give analytical answers to the above questions. Unexpected
      gains in sensitivity are reported for one of the most commonly used experimental
      building blocks in NMR spectroscopy. Surprisingly, in the case when longitudinal
      relaxation is small, the relaxation optimized pulse elements (ROPE) that transfer
      maximum polarization between coupled spins are longer than conventional
      sequences.

PMID- 12810015
TI  - Diffusion-relaxation correlation in simple pore structures.
AB  - The effects of independent encoding for relaxation and for diffusion using
      separate time and gradient dimensions are calculated for spins diffusing in plane
      parallel and spherical pores with relaxing walls. Two-dimensional inverse Laplace
      transformation is used to obtain computed (D,T(2)) maps for both geometries, in
      the regime in which the dimensionless diffusion coefficient is less than unity
      and the dimensionless relaxation parameter of order unity or greater. It is shown
      that there exist two distinct branches on the (D,T(2)) maps, one with diffusion
      and relaxation strongly correlated and one in which the diffusion coefficients
      vary widely independently of relaxation.

PMID- 12810016
TI  - The equivalence between off-resonance and on-resonance pulse sequences and its
      application to steady-state free precession with diffusion in inhomogeneous
      fields.
AB  - We show that the spin dynamics of any pulse sequence with off-resonant pulses is
      identical to that of a modified sequence with on-resonant pulses, including
      relaxation and diffusion effects. This equivalence applies to pulse sequences
      with arbitrary offset frequency deltaomega(0) which may exceed the RF field
      strength omega(1). Using this approach, we examine steady-state free precession
      (SSFP) in grossly inhomogeneous fields. We show explicitly that the magnitude of
      the magnetization for each mode at an offset frequency deltaomega(0) is equal to
      that for SSFP with on-resonance pulses of rescaled amplitude, with the same
      dependence on relaxation times and diffusion coefficient. The rescaling depends
      on offset frequency and RF field strength. The theoretical results have been
      tested experimentally and excellent agreement is found.

PMID- 12810017
TI  - 170 nm nuclear magnetic resonance imaging using magnetic resonance force
      microscopy.
AB  - We demonstrate one-dimensional nuclear magnetic resonance imaging of the
      semiconductor GaAs with 170 nm slice separation and resolve two regions of
      reduced nuclear spin polarization density separated by only 500 nm. This was
      achieved by force detection of the magnetic resonance, magnetic resonance force
      microscopy (MRFM), in combination with optical pumping to increase the nuclear
      spin polarization. Optical pumping of the GaAs created spin polarization up to 12
      times larger than the thermal nuclear spin polarization at 5K and 4T. The
      experiment was sensitive to sample volumes of 50 microm(3) containing
      approximately 4 x 10(11)71 Ga/Hz. These results demonstrate the ability of force
      detected magnetic resonance to apply magnetic resonance imaging to semiconductor
      devices and other nanostructures.

PMID- 12810018
TI  - Measurement of small spin-spin splittings in the presence of chemical exchange:
      case of deuteriated water.
AB  - A new implementation of a described data processing for measuring small scalar
      coupling constant J is proposed. It is applied particularly to situations where
      the coupling constant is around the linewidth at half-height, and in the presence
      of chemical exchange. This modified data processing uses only a simple "one
      pulse" experiment instead of a series of spin echoes experiments required by the
      previous processing. The FID recorded in the one pulse experiment is used by a
      reconstitution program to generate a set of signals, which are analyzed in the
      time domain to obtain a spectrum where the scalar coupling constant is apparently
      multiplied by n+1, where n is positive. The new processing is tested with
      simulated spectra. The coupling constant between proton and deuterium is measured
      in the proton spectrum of a solution of 80% of D(2)O and 20% of H(2)O. It was
      found to be J=1.54+/-0.01 Hz.

PMID- 12810019
TI  - Self-diffusion coefficient by single-sided NMR.
AB  - It is presented a novel method for the measure of the self-diffusion coefficient.
      The method exploits the fixed gradient of an open magnet, as that used in single
      sided NMR, and it does not use prior information on T(2). The approach presented
      in this paper can be practiced also on the fringe field of superconducting
      magnets and it is based on the construction of the ratios between echoes taken at
      different interpulses separation in a Carr-Purcell-Meiboom-Gill pulse sequence.
      The determination of the self-diffusion coefficient facilitates the estimate of
      T(2) because the transverse relaxation results almost influenced by the molecular
      diffusion effect, also at the shorter interpulses time, when it is measured in
      field strongly inhomogeneous.

PMID- 12810020
TI  - Flow effects in long-range dipolar field MRI.
AB  - Incoherent spin motion, such as diffusion, can lead to significant signal loss in
      multiple spin echoes (MSE) experiments, sometimes to its complete extinction.
      Coherent spin motion, such as laminar flow, can also modify the magnetization in
      MSE imaging and yield additional contrast. Our experimental results indicate that
      MSE is flow-sensitive. Our theoretical analysis and experimental results show how
      the effect of the distant dipolar field can be annihilated by flow. This effect
      can be quantified by directly solving the nonlinear Bloch equation, taking into
      account the deformation of the dipolar field by motion. Unexpected results have
      been observed, such as a recovery of the dipolar interaction due to flow in the
      "magic angle" condition.

PMID- 12810021
TI  - Separation of velocity distribution and diffusion using PFG NMR.
AB  - Pulsed field gradient (PFG) NMR is applied to investigate flow processes. In this
      case the NMR signal experiences phase modulation due to flow and signal
      attenuation due to the distribution of velocities. The velocity distribution
      consists of one part originating from diffusion and of a second part, the
      distribution of the directed motion. The usual PFG-experiment in which the
      gradient strength is incremented cannot distinguish between both. Incrementing
      velocity at constant gradient strength keeps the contribution from diffusion
      constant but changes the absolute width of the velocity distribution. So the
      signal is attenuated again, but only due to the distribution of the directed
      motion. The phase modulation as a signature of flow is not affected by this
      strategy, because velocity and gradient strength are Fourier conjugated. The key
      advantage of this approach is the possibility of measuring very low velocities,
      which only cause a very slight phase modulation that is easily covered by
      diffusion. The method is discussed here for very slow flow in a rheometer cell.

PMID- 12810022
TI  - Chain dynamics in the low-temperature phases of lipid membranes by electron spin
      echo spectroscopy.
AB  - Spin-echo decays of spin-labelled phospholipids have been recorded to study the
      chain dynamics in the low-temperature phases of dipalmitoyl phosphatidylcholine
      membranes with and without 50 mol% cholesterol. The phase-memory relaxation time,
      T(2M), depends on the position of spin-labelling in the sn-2 chain, and on the
      presence of cholesterol. A biphasic temperature dependence of T(2M) is obtained
      over the range 150-270 K. Echo-detected field-swept absorption EPR spectra were
      recorded as a function of the echo delay time, tau. The echo-detected EPR
      lineshapes show a strong dependence on tau, revealing anisotropic phase
      relaxation arising from torsional chain motions. Cholesterol has a large effect
      on torsional oscillations about the chain long axis. Small-amplitude chain
      motions in the low-temperature phases may be important for cryopreservation of
      membranes.

PMID- 12810023
TI  - Measurement of spin-lattice relaxation times in EPR with enhanced orientation
      selectivity.
AB  - Two schemes for the measurement of orientation-dependent spin-lattice relaxation
      times are introduced, which combine the inversion-recovery experiment with
      electron-Zeeman-resolved or right-angle wiggling EPR. The principles of the
      experiments are outlined and their performance is illustrated by examples of
      application. With the electron Zeeman-resolved approach the relaxation times of
      two metal complexes with different g values are unraveled, whereas with right
      angle wiggling the orientation-dependent relaxation behavior of a metal complex
      with large hyperfine anisotropy is analyzed.

PMID- 12810024
TI  - Internal consistency of NMR data obtained in partially aligned biomacromolecules.
AB  - A method of testing structure-related NMR data prior to structure calculations is
      presented. The test is applicable to second rank tensor interactions (dipolar
      coupling, anisotropic chemical shielding, and quadrupolar interaction) observed
      in partially aligned samples of biomacromolecules. The method utilizes the fact
      that only limited number of frequencies corresponding to the mentioned
      interactions can be measured independently in a rigid fragment of the
      macromolecule. Additional values can be predicted as linear combinations of the
      set of independent frequencies. Internal consistency of sufficiently large sets
      of frequencies measured in individual molecular fragments is tested by comparing
      the experimental data with their predicted values. The method requires only
      knowledge of local geometry (i.e., definition of the interaction tensors in the
      local coordinate frames of the fragments). No information about the alignment or
      shape of the molecule is required. The test is best suited for planar fragments.
      Application to peptide bonds and nucleic acid bases is demonstrated.

PMID- 12810025
TI  - Echo-planar rotating-frame imaging.
AB  - A new rotating-frame imaging method that produces a complete cross section of an
      object in a single experiment is reported. The echo planar rotating frame imaging
      (EPROFI) technique uses two perpendicular RF gradients for two-dimensional
      spatial encoding and fully exploits the formation of rotary echoes for fast
      sampling of spatial frequencies. The acquisition scheme yields the Fourier
      transform of the spin distribution on Cartesian coordinates for straightforward
      image reconstruction. Implementation of the technique on a low-field portable NMR
      probe is described and results are presented for test objects with different
      geometries.

PMID- 12810026
TI  - SCAM-STMAS: satellite-transition MAS NMR of quadrupolar nuclei with self
      compensation for magic-angle misset.
AB  - Several methods are available for the acquisition of high-resolution solid-state
      NMR spectra of quadrupolar nuclei with half-integer spin quantum number.
      Satellite-transition MAS (STMAS) offers an approach that employs only
      conventional MAS hardware and can yield substantial signal enhancements over the
      widely used multiple-quantum MAS (MQMAS) experiment. However, the presence of the
      first-order quadrupolar interaction in the satellite transitions imposes the
      requirement of a high degree of accuracy in the setting of the magic angle on the
      NMR probehead. The first-order quadrupolar interaction is only fully removed if
      the sample spinning angle, chi, equals cos(-1)(1/3) exactly and rotor
      synchronization is performed. The required level of accuracy is difficult to
      achieve experimentally, particularly when the quadrupolar interaction is large.
      If the magic angle is not set correctly, the first-order splitting is
      reintroduced and the spectral resolution is severely compromised. Recently, we
      have demonstrated a novel STMAS method (SCAM-STMAS) that is self-compensated for
      angle missets of up to +/-1 degrees via coherence transfer between the two
      different satellite transitions ST(+)(m(I)=+3/2<-->+1/2) and ST(-)(m(I)=-1/2<-->
      3/2) midway through the t(1) period. In this work we describe in more detail the
      implementation of SCAM-STMAS and demonstrate its wider utility through 23Na
      (I=3/2), 87 Rb (I=3/2), 27 Al (I=5/2), and 59 Co (I=7/2) NMR. We discuss
      linewidths in SCAM-STMAS and the limits over which angle-misset compensation is
      achieved and we demonstrate that SCAM-STMAS is more tolerant of temporary
      spinning rate fluctuations than STMAS, resulting in less "t(1) noise" in the two
      dimensional spectrum. In addition, alternative correlation experiments, for
      example involving the use of double-quantum coherences, that similarly display
      self-compensation for angle misset are investigated. The use of SCAM-STMAS is
      also considered in systems where other high-order interactions, such as third
      order quadrupolar effects or second-order quadrupole-CSA cross-terms, are
      present. Finally, we show that the sensitivity of the experiment can be improved
      through the use of amplitude-modulated pulses.

PMID- 12810027
TI  - Impurity proton NMR signals from common "proton-free" laboratory materials.
AB  - For the study of small samples (tens of microns cubed) by NMR, impurities from
      the environment and construction materials (Teflon, Kel-F, glass NMR tubes, etc.)
      can dominate the signal, in particular for proton NMR. Using pulsed NMR with a
      resolution of several microseconds, we have studied a number of common
      construction materials considered to be proton-free and find considerable proton
      impurity. We present results in terms of impurity proton spins per milligram and
      discuss procedures to minimize the effects of impurity signal.

PMID- 12810028
TI  - Selective excitation in pulsed EPR of a spin-correlated triplet-radical pair.
AB  - Experiments are described in which a low-amplitude microwave pulse excites only
      one out of three allowed transitions of the quinone radical (Q(A)(-)) in a spin
      correlated triplet-radical pair 3PQ(A)(-) of the bacterial photosynthetic
      reaction center. A second high-amplitude pulse produces a FID whose temporal
      shape is strongly modulated with frequencies determined by electron-electron
      dipolar interaction in the pair. The FID is detected in both the in-phase and the
      out-of-phase channels. The out-of-phase FID is a result of switching off the
      magnetic dipolar interaction between 3P and Q(A)(-) due to decay of 3P during the
      time interval between the two pulses. Refocusing of FID by an additional non
      selective pulse allows a dead-time free measurement of this modulation. The
      influence of the dead-time problem on the distance determination is discussed.

PMID- 12810029
TI  - Anisotropic motion effects in CW non-linear EPR spectra: relaxation enhancement
      of lipid spin labels.
AB  - Continuous-wave (CW) EPR measurements of enhancements in spin-lattice (T(1)-)
      relaxation rate find wide application for determining spin-label locations in
      biological systems. Often, especially in membranes, the spin-label rotational
      motion is anisotropic and subject to an orientational potential. We investigate
      here the effects of anisotropic diffusion and ordering on non-linear CW-EPR
      methods for determining T(1) of nitroxyl spin labels. Spectral simulations are
      performed for progressive saturation of the conventional in-phase, first-harmonic
      EPR signal, and for the first-harmonic absorption EPR signals detected 90 degrees
      -out-of-phase with respect to the Zeeman field modulation. Motional models used
      are either rapid rotational diffusion, or strong-jump diffusion of unrestricted
      frequency, within a cone of fixed maximum amplitude. Calculations of the T(1)
      sensitive parameters are made for both classes of CW-experiment by using motional
      parameters (i.e., order parameters and correlation times), intrinsic homogeneous
      and inhomogeneous linewidth parameters, and spin-Hamiltonian hyperfine- and g
      tensors, that are established from simulation of the linear CW-EPR spectra.
      Experimental examples are given for spin-labelled lipids in membranes.

PMID- 12810030
TI  - Enhanced triple-quantum excitation in 13C magic-angle spinning NMR.
AB  - We describe a new method for exciting triple-quantum coherences in 13C-labelled
      powder samples under MAS. The proposed method combines selective double-quantum
      excitation with rotational resonance and frequency-selective composite pulses.
      The spin dynamics of this new method are described theoretically. Numerical
      calculations of the spin dynamics are compared to experimental results on fully
      13C-labelled L-alanine. The observed triple-quantum filtering efficiency is
      around 10% for the most intense spectral peak. The method is also demonstrated on
      other fully 13C-labelled compounds, including a uniformly 13C-labelled amino
      acid.

PMID- 12810031
TI  - High frequency and field EPR spectroscopy of Mn(III) complexes in frozen
      solutions.
AB  - We have performed high-frequency and -field electron paramagnetic resonance
      (HFEPR) experiments on two complexes of high-spin Mn(III) (3d(4),S=2):
      mesotetrasulfonato-porphyrinatomanganese(III) (Mn(TSP)) and [(R,R)-(-)-N,N(')
      bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III)]
      (Mn(salen)). The main aim of this work was to qualitatively and quantitatively
      characterize the conditions suitable for HFEPR of high-spin transition metal
      complexes in frozen solutions, and compare them with experiments performed on
      solid samples. Mn(TSP) is a porphyrin complex soluble in water, in contrast to
      most metalloporphyrins. Mn(salen), often referred to as Jacobsen's catalyst, is a
      complex widely used in organic synthesis for alkene epoxidation, and is soluble
      in organic solvents. High-quality HFEPR signals were observed for solid state
      Mn(TSP), as has been previously shown for many Mn(III) complexes. The present
      study is, however, the first to report high-quality HFEPR spectra of a Mn(III)
      complex in frozen aqueous solution. Analysis of the data yielded the following
      spin Hamiltonian parameters: S=2; D=-3.16+/-0.02 cm(-1), E=0, and isotropic
      g=2.00(2). No X-band EPR signals were observed for Mn(TSP), which is a
      consequence of this being a rigorously axial spin system. Mn(salen), in contrast,
      did not give good quality HFEPR spectra in the solid state, but high-quality
      HFEPR spectra were recorded in frozen organic solutions. Analysis of the data
      yielded the following spin Hamiltonian parameters: S=2; D=-2.47+/-0.02 cm(-1),
      |E|=0.17+/-0.01 cm(-1), and isotropic g=2.00(2). These values differ from those
      reported using X-band parallel mode EPR [J. Am. Chem. Soc. 123 (2001) 5710], as
      discussed in the text. Therefore, a comparison between HFEPR and parallel-mode X
      band spectroscopy is made. Finally, the concentration sensitivity aspect of HFEPR
      spectroscopy is also discussed.

PMID- 12810032
TI  - Analysis of the tuning and operation of reflection resonator EPR spectrometers.
AB  - This paper investigates basic characteristics of the electron paramagnetic
      resonance (EPR) signal obtained from spectrometers employing reflection
      resonators. General equations are presented which reveal the phase and amplitude
      dependence on instrumental parameters of both components of the continuous wave
      (CW) EPR signal (absorption and dispersion). New phase vector diagrams derived
      from these general equations are presented for the analysis of the EPR response.
      The dependence of the phase and absolute value of the CW EPR signal on the local
      oscillator (LO) phase and on resonator offset and coupling is presented and
      analyzed. The EPR spectrometer tuning procedures for both balanced and unbalanced
      heterodyne receivers are analyzed in detail using the new phase diagrams.
      Extraneous signals at the RF input of the microwave receiver (resulting from
      circulator leakage and reflections in the resonator transmission line) have been
      taken into account and analyzed. It is shown that a final tuning condition that
      corresponds to an extremum of the receiver output as a function of the resonator
      frequency is necessary and sufficient for the acquisition of pure absorption
      signal. This condition is universal: it applies to all spectrometer
      configurations in all frequency ranges. High Frequency EPR spectrometer (130 GHz)
      data are used to generate experimental phase diagrams that illustrate the
      theoretical concepts presented in the paper. Conditions are presented under which
      the absorption signal can be measured with complete suppression of the
      dispersion, independent of the mutual frequency offset between the microwave
      source and the EPR sample resonator. Equations describing the approximate
      relationship between changes of the resonator properties (Q-factor and frequency)
      and paramagnetic susceptibility are derived and analyzed.

PMID- 12810033
TI  - Chemical shift referencing in MAS solid state NMR.
AB  - Solid state 13C magic angle spinning (MAS) NMR spectra are typically referenced
      externally using a probe which does not incorporate a field frequency lock.
      Solution NMR shifts on the other hand are more often determined with respect to
      an internal reference and using a deuterium based field frequency lock. Further
      differences arise in solution NMR of proteins and nucleic acids where both 13C
      and 1H shifts are referenced by recording the frequency of the 1H resonance of
      DSS (sodium salt of 2,2-dimethyl-2-silapentane-5-sulphonic acid) instead of TMS
      (tetramethylsilane). In this note we investigate the difficulties in relating
      shifts measured relative to TMS and DSS by these various approaches in solution
      and solids NMR, and calibrate adamantane as an external 13C standard for solids
      NMR. We find that external chemical shift referencing of magic angle spinning
      spectra is typically quite reproducible and accurate, with better than +/-0.03
      ppm accuracy being straight forward to achieve. Solid state and liquid phase NMR
      shifts obtained by magic angle spinning with external referencing agree with
      those measured using typical solution NMR hardware with the sample tube aligned
      with the applied field as long as magnetic susceptibility corrections and solvent
      shifts are taken into account. The DSS and TMS reference scales for 13C and 1H
      are related accurately using MAS NMR. Large solvent shifts for the 13C resonance
      in TMS in either deuterochloroform or methanol are observed, being +0.71 ppm and 
      0.74 ppm from external TMS, respectively. The ratio of the 13C resonance
      frequencies for the two carbons in solid adamantane to the 1H resonance of TMS is
      reported.

PMID- 12810034
TI  - Evolutionary developmental psychology: introduction to the special issue.

PMID- 12810035
TI  - Infants perceiving and acting on the eyes: tests of an evolutionary hypothesis.
AB  - It has been hypothesized that an evolutionarily ancient mechanism underlies the
      ability of human infants to detect and act upon the direction of eye gaze of
      another human face. However, the evidence from behavioral studies with infants is
      also consistent with a more domain-general system responsive to the lateral
      motion of stimuli regardless of whether or not eyes are involved. To address this
      issue three experiments with 4-month-old infants are reported that utilize a
      standard face-cueing paradigm. In the first experiment an inverted face was used
      to investigate whether the motion of the pupils elicits the cueing effect
      regardless of the surrounding face context. In the second experiment pupil motion
      and eye gaze direction were opposed, allowing us to assess their relative
      importance. In a third experiment, a more complex gaze shift sequence allowed us
      to analyse the importance of beginning with a period of mutual gaze. Overall, the
      results were consistent with the importance of the perceived direction of motion
      of pupils. However, to be effective in cueing spatial locations this motion needs
      to be preceded by a period of direct mutual gaze (eye contact). We suggest that
      evolution results in information-processing biases that shape and constrain the
      outcome of individual development to eventually result in adult adaptive
      specializations.

PMID- 12810036
TI  - Strategies of control, aggression, and morality in preschoolers: an evolutionary
      perspective.
AB  - Moral reasoning, moral affect, social problem solving skills, and social
      preferences were assessed in 163 ethnically mixed preschoolers (2.86-5.95 years).
      Participants were rated by their teachers on prosocial and coercive strategies of
      control, success at resource control, and aggression (overt and relational).
      Based on their employment of coercive and prosocial strategies of resource
      control, the children were categorized as bistrategic controllers, coercive
      controllers, prosocial controllers, noncontrollers, or typicals. Teacher-rated
      relational aggression was positively associated with moral maturity in girls.
      Bistrategic controllers, although aggressive, were morally mature and preferred
      play partners by their peers. The results are discussed in terms of hypotheses
      that arise from evolutionary theory which suggests that highly effective resource
      controllers would be simultaneously aggressive and yet well aware of moral norms.
      The findings are contrasted with alternative hypotheses that might arise
      variously from traditional and prevailing approaches.

PMID- 12810037
TI  - Children's performance on a false-belief task is impaired by activation of an
      evolutionarily-canalized response system.
AB  - We examine whether children's performance on a false-belief task is impaired by
      task content that activates an early-developing, prepotent motivational system:
      predator-avoidance. In two studies (N = 46 and N = 37), children aged 3-4 years
      completed variants of a false-belief task that involved predator-avoidance,
      playmate-avoidance, prey-seeking, and playmate-seeking, respectively. The
      proportion of correct answers on the playmate-avoidance task (Study 1: 52%; Study
      2: 51%) was significantly greater than the proportion of correct answers on the
      analogous predator-avoidance task (Study 1: 28%; Study 2: 22%). This difference
      was not an artifact of children generally performing better on playmate stories
      than on predator-prey stories. The findings are consistent with the hypothesis
      that activation of the predator-avoidance system generates prepotent response
      patterns that pre-empt full consideration of the mental states of the prey
      characters in false-belief stories.

PMID- 12810038
TI  - A sexual selection theory longitudinal analysis of sexual segregation and
      integration in early adolescence.
AB  - The three objectives in this longitudinal study were motivated by sexual
      selection theory. The theory specifies the role of sexually segregated groups and
      the effects of dominance in male groups and relational/indirect aggression in
      female groups for heterosexual relationships. Using a multi-method, multi
      informant, longitudinal design we studied youngsters (N=138) across their first
      two years of middle school. First, we examined the nature of change in
      segregation and dating popularity across two years during early adolescence.
      Second, a model derived from sexual selection theory is tested to explain the
      ways in which boys and girls are nominated for hypothetical dates (dating
      popularity). Third, we examined the role of "poke and push courtship" behavior in
      boys' and girls' dating popularity. Results indicate that although groups did not
      become more integrated with time, changes in peer group sexual integration co
      varied dynamically with dating popularity. Secondly, dominance-related strategies
      were more important for boys than girls in dating popularity whereas indirect, or
      relational, aggression strategies were more important for girls than boys. Third,
      "poke and push courtship" behaviors did not influence peer group integration or
      dating.

PMID- 12810039
TI  - Possible olfaction-based mechanisms in human kin recognition and inbreeding
      avoidance.
AB  - Three studies explored kin recognition through olfaction. In Study I, adults
      (N=22) were tested for ability to identify the odors of themselves; their mother;
      their father; a sister; a brother; a familiar, unrelated individual; and a
      stranger. Acquaintances were identified as accurately as biological kin,
      implicating an association mechanism. However, biological kin were often
      confused, implicating phenotypic matching. Same-sex kin were confused more than
      opposite-sex kin, but mainly when same-sex kin had odors of similar intensity.
      Study II implicated phenotypic matching. Mothers (N=18) could identify their
      biological children but not their stepchildren. The preadolescent children (N=37)
      identified their full siblings but not half-siblings or stepsiblings. Thus,
      olfactory cues may help mediate favoritism of blood relatives. In Study III,
      mutual olfactory aversion occurred only in the father-daughter and brother-sister
      nuclear family relationships. Recognition occurred between opposite-sex siblings
      but not same-sex siblings. Thus, olfaction may help mediate the development of
      incest avoidance during childhood (the Westermarck effect).

PMID- 12810040
TI  - Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni:
      correlation with their octanol-water partition coefficients.
AB  - The experiments described here report on the correlation between the ex vivo
      diffusion of different benzimidazole (BZD) anthelmintics into the cestode
      parasite Moniezia benedeni, and their octanol-water partition coefficients
      (P.C.). The characterisation of the drug diffusion process into target parasites
      is relevant to understand the mechanism of drug penetration and the
      pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M.
      benedeni, used as a helminth parasite model, were obtained from untreated cattle
      killed at the local abattoir. The collected parasites were incubated (5-210 min)
      with either fenbendazole (FBZ), albendazole (ABZ), ricobendazole (RBZ),
      oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ),
      in a Kreb's Ringer Tris buffer medium at a final concentration of 5 nmol/ml.
      After the incubation time elapsed, samples of parasite material were chemically
      extracted and prepared for high performance liquid chromatography (HPLC) analysis
      to measure drug/metabolite concentrations. Additionally, the octanol-water P.C.
      for each molecule was estimated as an indicator of drug lipophilicity, using
      reversed phase HPLC analysis. All the incubated drugs were recovered from the
      tapeworms as early as 5 min post incubation. There was a high correlation
      (r=0.87) between drug lipophilicity, expressed as octanol-water P.C. (Log P), and
      drug availability within the parasite. The most lipophilic BZD compounds (FBZ,
      ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative
      higher concentrations within the tapeworm compared to those drugs with the lowest
      P.C. values. Considering the results from the current and previous studies, it is
      clear that passive diffusion is a major mechanism of BZD penetration into cestode
      parasites, where lipid solubility is a determinant factor influencing the
      diffusion of these anthelmintic molecules through the parasite tegument.

PMID- 12810041
TI  - Entamoeba histolytica: a beta 1 integrin-like fibronectin receptor assembles a
      signaling complex similar to those of mammalian cells.
AB  - During tissue invasion, Entamoeba histolytica trophozoites interact with
      endothelial cells and extracellular matrix (ECM) proteins such as fibronectin
      (FN), collagen, and laminin. It has been demonstrated that trophozoites interact
      with FN through a beta1 integrin-like FN receptor (beta 1EhFNR), activating
      tyrosine kinases. In order to characterize the signaling process triggered by the
      amoebic receptor, activation, and association of tyrosine kinases and structural
      proteins were determined. As a result of FN binding by the beta 1EhFNR, the
      receptor itself, FAK, and paxillin were phosphorylated in tyrosine. Co
      immunoprecipitation experiments showed that a multimolecular signaling complex
      was formed by the amoebic FN receptor, FAK, paxillin, and vinculin. These results
      strongly suggest that a signaling pathway, similar to the one used in mammalian
      cells, is activated when E. histolytica trophozoites adhere to FN.

PMID- 12810042
TI  - Brugia pahangi and Wolbachia: the kinetics of bacteria elimination, worm
      viability, and host responses following tetracycline treatment.
AB  - Wolbachia spp., first reported from filariae nearly 30 years ago, have been
      suggested to contribute to the pathogenesis associated with human filarial
      infection. Tetracycline has been used to cure filariae of Wolbachia, as a novel
      means of chemotherapeutic treatment for both ocular and lymphatic filariasis.
      Tetracycline treatment of L4 or adult Brugia pahangi in vivo resulted in
      Wolbachia clearance. Less tetracycline was required to clear Wolbachia when
      treatment began at the L4 stage, compared with adults. Female worms died earlier
      than male worms when tetracycline was administered at the L4 stage. In all cases,
      Wolbachia clearance was closely associated with worm death. Worm recoveries
      decreased following the L4-L5 molt, suggesting tetracycline does not interrupt
      molting in this model system. Despite worm death and the assumed release of both
      bacterial- and worm-derived molecules, differences in inflammatory cell
      population and T cell cytokine mRNA profiles were negligible between tetracycline
      treated and non-treated B. pahangi infected gerbils. These data suggest the
      contribution of Wolbachia to the in vivo induction of the gerbil immune response
      to B. pahangi may be small.

PMID- 12810044
TI  - Trypanosoma vivax: mechanical transmission in cattle by one of the most common
      African tabanids, Atylotus agrestis.
AB  - The role of mechanical vectors in the transmission of African livestock
      trypanosomes has always been controversial relative to tsetse flies, their
      cyclical vectors. An experiment was carried out in Burkina Faso to demonstrate
      mechanical transmission of Trypanosoma vivax by one of the most common tabanids
      in Africa: Atylotus agrestis. Eight heifers (crossbred zebuxBaoule), free of
      trypanosome infection, were kept in a corral covered by a mosquito net, together
      with two heifers infected experimentally with a local stock of T. vivax. On
      average, 324 A. agrestis, freshly captured with Nzi traps, were introduced daily
      over 20 days. Parasitological, PCR and serological examinations were carried out
      regularly to assess infections and levels of parasitaemia. Microscopic
      examination of buffy-coats indicated that five of the eight receiver-heifers were
      infected on days 8, 13, 32, 41, and 48. PCR results indicated that these five
      heifers were already infected by day 13. Mechanical transmission of T. vivax by
      A. agrestis was demonstrated unequivocally, at a high rate (63% in 13-20 days).
      Conditions of transmission in this experiment are discussed in terms of natural
      rates of challenge. The importance of tabanids as mechanical vectors of T. vivax
      should be re-considered, in light of these results. Creation of tsetse free zones
      in Africa will generally lead to the disappearance of T. congolense, T. brucei,
      and most often T. vivax as well; however, in areas where T. vivax can be
      mechanically transmitted, clearance of tsetse may not be sufficient to eradicate
      livestock trypanosomosis.

PMID- 12810043
TI  - Trypanosoma cruzi: allelic comparisons of the actin genes and analysis of their
      transcripts.
AB  - Two allelic genomic fragments containing actin genes from Trypanosoma cruzi were
      isolated and characterized. One allele comprises two complete tandem repeats of a
      sequence encoding an actin gene. In the other, only one actin gene is found. Each
      one of these three gene copies encode for a complete and identical potential
      protein of 376 amino acids which is 93% similar with its homolog from Trypanosoma
      brucei. Northern hybridizations of both total and polysomal RNA from
      epimastigotes demonstrated the presence of an actin polyadenylated mRNA of about
      1.6 kb. Actin transcripts processing sites were determined by 5(')- and 3(')
      RACE. The obtained sequence data demonstrates that actin genes from both alleles
      are expressed. The stability of actin mRNA was found to be similar to the one
      exhibited by the ribosomal protein S4 mRNA as an internal reference. A time
      course analysis of cultured epimastigotes showed a novel behaviour in which actin
      mRNA steady state concentration peaks during the transition from the logarithmic
      to the stationary phase of growth.

PMID- 12810045
TI  - Trichomonas vaginalis: evaluating capsid proteins of dsRNA viruses and the dsRNA
      virus within patients attending a sexually transmitted disease clinic.
AB  - Some isolates of Trichomonas vaginalis, the number one, non-viral sexually
      transmitted disease agent, are infected with one or several distinct double
      stranded (ds)-RNA virus. Immune rabbit anti-capsid serum (IRS) reacted with the
      capsid protein of purified dsRNA virus of a subset of the virus-infected T.
      vaginalis isolates. A monoclonal antibody (mAb) that recognized the capsid
      protein reactive with the IRS was generated. Analysis of the virus capsid protein
      of virus-infected isolates by probing nitrocellulose blots with mAb revealed
      diversity among immunoreactivity and in the size of the reactive capsid protein.
      Despite difficulties in visualizing virus within parasites by cross-section
      electron microscopy, gold-conjugated mAb readily labeled the cytoplasm of virus
      positive trichomonads. Finally and importantly, isolates infecting patients
      attending an STD clinic, 75% of which were virus-positive isolates, had capsid
      protein of the same size detected by mAb present in all dsRNA viruses.

PMID- 12810046
TI  - Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral
      treatment for visceral leishmaniasis.
AB  - Drugs currently available for visceral leishmaniasis treatment are potentially
      toxic, have to be administered by parenteral route and frequently give rise to
      drug resistance, due to the involvement of P-glycoproteins (P-gp) in Leishmania.
      The purpose of this study was to investigate a possible inhibitory effect of 2n
      propylquinoline (2nPQ) on P-gp activity. 2nPQ is a new oral anti-leishmanial drug
      that has demonstrated its efficacy in BALB/c infected mice with Leishmania
      donovani [Antimicrob. Agents Chemother. 37 (1993) 859]. Rat everted gut sacs and
      human intestinal Caco-2 cell lines were used to study the effect of 2nPQ on P-gp
      activity. Our results demonstrate an inhibitory effect of 2nPQ on the P-gp
      activity with two P-gp substrates (rhodamine 123 and digoxin), two P-gp
      inhibitors (cyclosporin A and verapamil), and in two different species. Alone or
      associated with other active drugs, 2nPQ would be very useful to control
      Leishmania Multi-Drug-Resistance and intestinal P-gp in humans with kala-azar.

PMID- 12810047
TI  - Brugia malayi: establishment in inbred and outbred strains of mice.
AB  - Immunocompetent mouse model for human filarial parasite Brugia malayi is urgently
      required in view of the paucity of commercial reagents for other susceptible
      rodent viz. mastomys and gerbil. Genes within the major histocompatibility
      complex have been reported to influence the susceptibility of mouse to helminth
      parasites. Attempts have therefore been made in the present investigation to
      experimentally infect various inbred strains of mice viz. NZB/BINJ, BALB/c, AKR,
      C(3)H, and SJL/J with H-2 haplotype (H-2: d, d, k, k, s, respectively) and
      outbred strains of mice viz. Parks and Swiss. Findings indicate that
      susceptibility of mice to B. malayi is strain associated. This is the first
      report on the successful completion of full developmental cycle of subperiodic B.
      malayi in NZB/BINJ, an immunocompetent mouse strain. In some of the other
      strains, partial development or low degree of establishment of worms was
      observed.

PMID- 12810048
TI  - Entamoeba invadens: inhibition of excystation and metacystic development by
      aphidicolin.
AB  - The effect of aphidicolin, a specific inhibitor of the replicative DNA
      polymerases, on the excystation and metacystic development of Entamoeba invadens
      was examined. The protein profile of metacystic amoebae and their immunogenicity
      in the presence and absence of aphidicolin were also examined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblotting. Excystation, which
      was assessed by counting the number of metacystic amoebae after the induction of
      excystation, was inhibited by aphidicolin in a concentration-dependent manner
      during incubation compared to the controls. Metacystic development, when
      determined by the number of nuclei in amoeba, was also inhibited by aphidicolin,
      because the percentage of 4-nucleate amoebae in cultures with aphidicolin during
      incubation was higher than that in cultures without the drug. The addition of
      aphidicolin to cultures at day 1 of incubation reduced the number of metacystic
      amoebae thereafter compared to cultures without the drug. The inhibitory effect
      of aphidicolin on excystation and metacystic development was reversed by removal
      of the drug. Pretreatment of cysts with aphidicolin before transfer to a growth
      medium containing the drug had no further effect on the excystation and
      metacystic development. Cellular proteins of metacystic amoebae with 4 nuclei,
      which were predominant even at day 3 in the cultures with aphidicolin, reacted
      strongly with rabbit anticyst serum absorbed with trophozoite proteins. In
      contrast, those of metacystic amoebae with 1 nucleus, which were predominant at
      day 3 in cultures without aphidicolin, no longer reacted with the absorbed
      anticyst serum, suggesting change in the expression of proteins during metacystic
      development.

PMID- 12810049
TI  - Toxoplasma gondii: analysis of the active site insertion of its ferredoxin
      NADP(+)-reductase by peptide-specific antibodies and homology-based modeling.
AB  - Apicomplexan parasites possess an apicoplast-localized redox system consisting of
      a plant-type ferredoxin-NADP(+)-reductase (FNR) and its redox partner ferredoxin,
      a small [2Fe-2S] protein. We show here that several apicomplexan FNRs contain
      unique amino acid insertions of various lengths which are located in close
      proximity to the enzymatically important FAD and ferredoxin-binding sites of
      these proteins. Using the insertion of the Toxoplasma gondii reductase as an
      example we raised epitope-specific antibodies against an 11 amino acids long
      peptide predicted to be surface-exposed within this insertion. This peptide was
      found to be immunogenic when presented to the immune system as part of a carrier
      protein, but also in its natural structural context in the whole recombinant
      protein, implying that the epitope is surface-exposed. Three-dimensional modeling
      of T. gondii FNR based on the known 3D-structure of maize root FNR predicts that
      the overall structure of plant and apicomplexan FNRs are very similar and that
      the 11 amino acids are part of an alpha-helix, looping out of the molecule.
      Collectively, these data suggest that the insertion in T. gondii FNR does not
      affect the overall structure of the protein but may have an effect on the binding
      dynamics of FAD, NADP(+), and/or ferredoxin to FNR.

PMID- 12810050
TI  - Conserved nucleotides surrounding the trans-splicing acceptor site and the
      translation initiation codon in Leishmania genes.

PMID- 12810051
TI  - Entamoeba histolytica: expression and DNA binding of CCAAT/enhancer-binding
      proteins are regulated through the cell cycle.

PMID- 12810052
TI  - Plasmodium falciparum: new vector with bi-directional promoter activity to stably
      express transgenes.

PMID- 12810053
TI  - Measurements of the free luminal ER Ca(2+) concentration with targeted "cameleon"
      fluorescent proteins.
AB  - The free ER Ca(2+) concentration, [Ca(2+)](ER), is a key parameter that
      determines both the spatio-temporal pattern of Ca(2+) signals as well as the
      activity of ER-resident enzymes. Obtaining accurate, time-resolved measurements
      of the Ca(2+) activity within the ER is thus critical for our understanding of
      cell signaling. Such measurements, however, are particularly challenging given
      the highly dynamic nature of Ca(2+) signals, the complex architecture of the ER,
      and the difficulty of addressing probes specifically into the ER lumen. Prompted
      by these challenges, a number of ingenious approaches have been developed over
      the last years to measure ER Ca(2+) by optical means. The two main strategies
      used to date are Ca(2+)-sensitive synthetic dyes trapped into organelles and
      genetically encoded probes, based either on the photoprotein aequorin or on the
      green fluorescent protein (GFP). The GFP-based Ca(2+) indicators comprise the
      camgaroo and pericam probes based on a circularly permutated GFP, and the
      cameleon probes, which rely on the fluorescence resonance energy transfer (FRET)
      between two GFP mutants of different colors. Each approach offers unique
      advantages and suffers from specific drawbacks. In this review, we will discuss
      the advantages and pitfalls of using the genetically encoded "cameleon" Ca(2+)
      indicators for ER Ca(2+) measurements.

PMID- 12810054
TI  - Cell-specific Ca(2+) responses in glucose-stimulated single and aggregated beta
      cells.
AB  - A rise in the cytoplasmic calcium concentration ([Ca(2+)](i)) is a key event for
      insulin exocytosis. We have recently found that the 'early [Ca(2+)](i) response'
      in single ob/ob mouse beta-cells is reproduced during consecutive glucose
      stimulations. It, therefore, appears that the response pattern is a
      characteristic of the individual beta-cell. We have now investigated if a cell
      specific [Ca(2+)](i) response is a general phenomenon in rodent beta-cells, and
      if it can be observed when cells are functionally coupled. With the use of the
      fura-2 technique, we have studied the 'early [Ca(2+)](i) response' in single
      dispersed beta-cells, in beta-cell clusters of different size and in intact
      islets from the ob/ob mouse during repeated glucose stimulation (20mM). beta
      Cells from lean mouse and rat, and intact islets from lean mouse were also
      investigated. Significant correlations between the first and second stimulation
      were found for the parameters lag-time for Ca(2+) rise (calculated as the time
      from start of stimulation of the cell until the first value above an extrapolated
      baseline), nadir of initial lowering (difference between the baseline and lowest
      [Ca(2+)](i) value), and peak height (difference between baseline and the highest
      [Ca(2+)](i) value of the first calcium peak) in single dispersed beta-cells, in
      'single beta-cell within a small cluster', in clusters of medium and large size,
      and in single dispersed beta-cells from lean mouse and rat. The lag-times for
      Ca(2+) rise and peak heights were correlated within the pairs of stimulation also
      in intact ob/ob islets. In summary, despite a large heterogeneity of the 'early
      [Ca(2+)](i) response' among individual cells, the lag-time for [Ca(2+)](i) rise,
      the nadir of initial lowering and the height of the first peak response can be
      identified as cell-specific markers in beta-cells.

PMID- 12810055
TI  - Effects of calcium buffers and calbindin-D28k upon histamine-induced calcium
      oscillations and calcium waves in HeLa cells.
AB  - The effects of the artificial Ca(2+) buffers EGTA and BAPTA upon histamine
      induced Ca(2+) oscillations and calcium waves were studied in HeLa cells. These
      events were also examined in HeLa cell lines transfected with the intracellular
      calcium-binding protein calbindin-D28k (CaBP; HeLa-CaBP) or the pCINeo vector
      alone (HeLa-pCINeo). High concentrations of the Ca(2+) indicators fluo-3 and fura
      2 significantly influenced the oscillatory pattern of intracellular Ca(2+) in
      HeLa-pCINeo cells exposed to 1 microM histamine. Loading cells with low
      concentrations of the cell-permeant esters of the artificial Ca(2+)-buffers EGTA
      or BAPTA, resulted in fewer cells with a distinct "baseline" oscillatory pattern,
      and loading with higher concentrations of BAPTA almost completely abolished them.
      In HeLa-CaBP cells, stimulation with 1 microM histamine resulted in individual
      Ca(2+) spikes that had a flattened profile when compared to control cells; peak
      [Ca(2+)](i) was lowered, the rate of increase in [Ca(2+)](i) was slower and
      transients were prolonged. When compared to HeLa-pCINeo cells, loading with EGTA
      or BAPTA, or transfection of CaBP, significantly reduced the propagation velocity
      (by up to 60%) of Ca(2+) waves induced by exposure to 100 microM histamine. We
      conclude that intracellular Ca(2+) buffering exerts a significant influence on
      global Ca(2+) responses in HeLa cells and the propagation of Ca(2+) waves that
      underlie them. The relative effectiveness of different Ca(2+) buffers, including
      CaBP, appears to be particularly dependent upon the rapidity of their binding
      kinetics, with BAPTA being the most effective.

PMID- 12810056
TI  - Ca(2+) oscillations regulated by Na(+)-Ca(2+) exchanger and plasma membrane
      Ca(2+) pump induce fluctuations of membrane currents and potentials in human
      mesenchymal stem cells.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) have the potential to
      differentiate into several types of cells. We have demonstrated spontaneous
      [Ca(2+)](i) oscillations in hMSCs without agonist stimulation, which result
      primarily from release of Ca(2+) from intracellular stores via InsP(3) receptors.
      In this study, we further investigated functions and contributions of Ca(2+)
      transporters on plasma membrane to generate [Ca(2+)](i) oscillations. In confocal
      Ca(2+) imaging experiments, spontaneous [Ca(2+)](i) oscillations were observed in
      193 of 280 hMSCs. The oscillations did not sustain in the Ca(2+) free solution
      and were completely blocked by the application of 0.1mM La(3+). When plasma
      membrane Ca(2+) pumps (PMCAs) were blocked with blockers, carboxyeosin or
      caloxin, [Ca(2+)](i) oscillations were inhibited. Application of Ni(2+) or
      KBR7943 to block Na(+)-Ca(2+) exchanger (NCX) also inhibited [Ca(2+)](i)
      oscillations. Using RT-PCR, mRNAs were detected for PMCA type IV and NCX, but not
      PMCA type II. In the patch clamp experiments, Ca(2+) activated outward K(+)
      currents (I(KCa)) with a conductance of 170+/-21.6pS could be recorded. The
      amplitudes of I(KCa) and membrane potential (V(m)) periodically fluctuated liked
      to [Ca(2+)](i) oscillations. These results suggest that in undifferentiated hMSCs
      both Ca(2+) entry through plasma membrane and Ca(2+) extrusion via PMCAs and NCXs
      play important roles for [Ca(2+)](i) oscillations, which modulate the activities
      of I(KCa) to produce the fluctuation of V(m).

PMID- 12810057
TI  - Similar Ca(2+)-signaling properties in keratinocytes and in COS-1 cells
      overexpressing the secretory-pathway Ca(2+)-ATPase SPCA1.
AB  - Mutations in the ubiquitously expressed secretory-pathway Ca(2+)-ATPase (SPCA1)
      Ca(2+) pump result in Hailey-Hailey disease, which almost exclusively affects the
      epidermal part of the skin. We have studied Ca(2+) signaling in human
      keratinocytes by measuring the free Ca(2+) concentration in the cytoplasm and in
      the lumen of both the Golgi apparatus and the endoplasmic reticulum. These
      signals were compared with those recorded in SPCA1-overexpressing and control COS
      1 cells. Both the sarco(endo)plasmic-reticulum Ca(2+)-ATPase (SERCA) and SPCA1
      can mediate Ca(2+) uptake into the Golgi stacks. Our results indicate that
      keratinocytes mainly used the SPCA1 Ca(2+) pump to load the Golgi complex with
      Ca(2+) whereas the SERCA Ca(2+) pump was mainly used in control COS-1 cells.
      Cytosolic Ca(2+) signals in keratinocytes induced by extracellular ATP or
      capacitative Ca(2+) entry were characterized by an unusually long latency
      reflecting extra Ca(2+) buffering by an SPCA1-containing Ca(2+) store, similarly
      as in SPCA1-overexpressing COS-1 cells. Removal of extracellular Ca(2+) elicited
      spontaneous cytosolic Ca(2+) transients in keratinocytes, similarly as in SPCA1
      overexpressing COS-1 cells. With respect to Ca(2+) signaling keratinocytes and
      SPCA1-overexpressing COS-1 cells therefore behaved similarly but differed from
      control COS-1 cells. The relatively large contribution of the SPCA1 pumps for
      loading the Golgi stores with Ca(2+) in keratinocytes may, at least partially,
      explain why mutations in the SPCA1 gene preferentially affect the skin in Hailey
      Hailey patients.

PMID- 12810058
TI  - The Ile2453Thr mutation in the ryanodine receptor gene 1 is associated with
      facilitated calcium release from sarcoplasmic reticulum by 4-chloro-m-cresol in
      human myotubes.
AB  - Central core disease (CCD) is a congenital disorder of skeletal muscle that is
      characterised histologically by typical central cores in type 1 skeletal muscle
      fibres. This disease is associated with malignant hyperthermia susceptibility and
      has been linked to the gene of skeletal muscle ryanodine receptor RYR1. In this
      study, we present a family with the spontaneous occurrence of the RYR1 Ile2453Thr
      mutation. Affected individuals were diagnosed as susceptible to malignant
      hyperthermia in the in vitro contracture test (IVCT) and showed histological
      signs of CCD. Myotubes were derived from the index patient. The calcium
      homeostasis in response to the ryanodine receptor agonist 4-chloro-m-cresol
      (4CmC) was investigated by calcium imaging using the Ca(2+)-sensitive fluorescent
      probe FURA 2. In the myotubes derived from the mutation carrier, the EC(50) of
      4CmC was reduced to 94 micro as compared to 201 microM in a control group of 16
      individuals non-susceptible to malignant hyperthermia. In the myotubes of the non
      affected family members, the EC(50) was found within the same range as that of
      the control group. The reduction of EC(50) indicates a facilitated calcium
      release from sarcoplasmic reticulum in the myotubes of the index patient
      suggesting that the RYR1 Ile2453Thr mutation is pathogenic for the malignant
      hyperthermia susceptibility and CCD of the two affected individuals.

PMID- 12810059
TI  - Involvement of capacitive calcium entry and calcium store refilling in
      osteoclastic survival and bone resorption process.
AB  - Bone resorption is closely dependent on osteoclastic survival and osteoclast
      apoptotic cell death could represent a key step at the end of this process. In
      order to precise the possible role of calcium movement in osteoclastic cell
      death, we investigated whether intracellular calcium store replenishment and
      capacitive calcium entry (CCE) are involved in osteoclastic survival and bone
      resorption. We demonstrate that (i). thapsigargin, a sarco-endoplasmic reticulum
      calcium ATPase pump (SERCA) blocker, decreases both osteoclastic survival and
      bone resorption process, (ii). 2-aminoethoxydiphenyl borate (2-APB) and SKF
      96365, two store-operated channel (SOC) blockers, dramatically decrease
      osteoclastic survival and bone resorption and (iii). culture in calcium-free
      medium and thapsigargin exposure synergically inhibit osteoclastic survival which
      falls dramatically to a value close to 0% (P<0.001). Inversely, osteoclastic
      survival increases significantly when thapsigargin-treated cells are cultured in
      the presence of 20mM calcium, suggesting that increasing extracellular calcium
      concentration stimulates osteoclasts survival when the filling of intracellular
      stores is prevented. Taken together, our data strongly suggest that in
      osteoclasts, calcium movements between cellular compartments involved in the
      regulation of calcium signalling, such as calcium stores refilling and CCE, are
      closely associated to the regulation of osteoclast survival and bone resorption.

PMID- 12810060
TI  - Differential functional interaction of two Vesl/Homer protein isoforms with
      ryanodine receptor type 1: a novel mechanism for control of intracellular calcium
      signaling.
AB  - Vesl/Homer proteins physically link proteins that mediate cellular signaling
      [Curr. Opin. Neurobiol. 10 (2000) 370; Trends Neurosci. 23 (2000) 80; J. Cell
      Sci. 113 (2000) 1851] and thereby influence cellular function [Nat. Neurosci. 4
      (2001) 499; Nature 411 (2001) 962]. A previous study reported that Vesl-1L/Homer
      1c (V-1L) controls the gain of the intracellular calcium activated calcium
      channel ryanodine receptor type 1 (RyR1) channel [J. Biol Chem. 277 (2002)
      44722]. Here, we show that the function of RyR1 is differentially regulated by
      two isoforms of Vesl-1/Homer-1, V-1L and Vesl-1S/Homer-1a (V-1S). V-1L increases
      the activity of RyR1 while important regulatory functions and pharmacological
      characteristics are preserved. V-1S alone had no effect on RyR1, even though,
      like V-1L, it is directly bound to the channel. However, V-1S dose-dependently
      decreased the effects of V-1L on RyR1, providing a novel mechanism for the
      regulation of intracellular calcium channel activity and calcium homeostasis by
      changing expression levels of Vesl/Homer proteins.

PMID- 12810061
TI  - Intercellular Ca(2+)-transient propagation in normal and high glucose solutions
      in rat retinal epithelial (RPE-J) cells during mechanical stimulation.
AB  - We investigated the effect of high glucose and modulation of protein kinase C
      (PKC) on the intercellular propagation of Ca(2+)-waves in a rat retinal pigment
      epithelial cell line (RPE-J cells) in order to compare its properties with the
      properties previously investigated in primary LE-RPE cells. The intercellular
      propagation of the Ca(2+)-waves in RPE-J cells was analyzed by fluorescence
      imaging confocal microscopy and fluorescence recovery after photobleaching
      (FRAP). In control conditions the maximal normalized fluorescence in the
      mechanically stimulated (MS) cell and the propagation towards the neighboring RPE
      J cells were similar to LE-RPE cells. As in LE-RPE cells, the propagation was
      reduced by the gap junction (GJ) blocker halothane, and FRAP experiments
      demonstrated the presence of functional GJ coupling. Similar to the effect in LE
      RPE cells, the propagation of the Ca(2+)-transient was reduced by 25 mM glucose.
      However, unlike LE-RPE cells, the neighboring RPE-J cells presented a Ca(2+)-rise
      of amplitude similar to that in normal glucose levels. PKC activation with 1
      microM PMA for 30 min resulted in inhibition of the Ca(2+)-wave propagation,
      which could be overcome by PKC downregulation as in LE-RPE cells. Cells grown for
      72 h in a high glucose solution in which PKC activity was downregulated, did not
      develop the inhibitory effect on Ca(2+)-wave propagation that was induced by
      elevated glucose levels. However, the effects were not as pronounced as in LE-RPE
      cells. We concluded that despite marked similarities, the transduction and the
      modulation of intercellular propagation of the Ca(2+)-transients in RPE-J cells
      are not identical to the mechanisms in primary LE-RPE cells.

PMID- 12810062
TI  - Increments in the concentrations of sodium and calcium in cell compartments of
      stretched mouse ventricular myocytes.
AB  - Increments in total intracellular sodium [Na] and calcium concentration [Ca],
      expected from stretch activation of non-selective cation current I(SAC), were
      quantified by means of electron probe microanalysis (EPMA) with 16 nm spatial
      resolution.Voltage-clamped mouse ventricular myocytes were stretched by
      increasing the distance between patch pipette and a cell-attached stylus by 20%.
      After 2 min stretch, cells were shock-frozen for EPMA. Stretch incremented [Na]
      in peripheral cytosol from 23 to 48 mM, central cytosol from 17 to 29 mM, central
      mitochondria from 10 to 21 mM, nuclear envelope from 43 to 71 mM, nucleus from 12
      to 24 mM. Stretch increased total [Ca] in peripheral cytosol from 570 to 840
      microM, central cytosol from 404 to 840 microM. Mitochondrial [Ca] did not
      change. Stretch increased [Ca] in both nucleus (from 180 to 300 microM) and
      nuclear envelope (from 933 to 1530 microM) suggesting a calcium barrier function
      for the envelope. Block of I(SAC) by 50 microM streptomycin abolished stretch
      induced increments in [Na] suggesting Na(+) influx with I(SAC) as underlying
      mechanism. Streptomycin abolished the stretch-induced increase in peripheral but
      not in central cytosolic [Ca], as if additional mechanisms to I(SAC) were
      involved in elevating central [Ca].

PMID- 12810063
TI  - Fractional Ca(2+) current through human neuronal alpha7 nicotinic acetylcholine
      receptors.
AB  - The neuronal alpha7 nicotinic acetylcholine (ACh) receptor is believed to be a
      highly Ca(2+) permeable ligand-gated receptor-channel. However, the contribution
      of Ca(2+) to cationic current generated by ACh has not yet been directly measured
      to date. Simultaneous fluorescence and whole-cell current measurements using the
      Ca(2+) indicator dye fura-2 were made in GH4C1 pituitary cells stably expressing
      human alpha7 receptors and the fractional Ca(2+) current (the proportion of whole
      cell current carried by Ca(2+); P(f)) was determined. We report that the P(f)
      value was 11.4+/-1.3%. This value was significantly larger than P(f) of human
      L248Talpha7 receptor mutant (P(f)=6.3+/-1.0%) and of rat alpha7 receptor
      (P(f)=8.8+/-1.5%) both determined in transiently transfected GH4C1 cells. In our
      knowledge, the findings here reported indicate the human alpha7 receptors are the
      most Ca(2+) conductive homomeric ligand-gated receptor-channels expressed in a
      heterologous cell system.

PMID- 12810064
TI  - Debt91, a putative zinc finger protein differentially expressed during epithelial
      morphogenesis.
AB  - In a differential screen for genes that might be important in the regulation of
      epithelial morphogenesis, we identified a novel gene, Debt91 (differentially
      expressed in branching tubulogenesis), which is up-regulated in an in vitro model
      of renal tubulogenesis and branching. Debt91 appears to encode a 381 amino acid
      molecule with high Ser and Thr composition and is highly conserved at its N
      terminus across species. Sequence analysis suggests that it is a coiled-coil
      nuclear phosphoprotein with zinc finger motifs at the N-terminal conserved
      region, which is rich in cysteine and histidine. Debt91 is located on mouse
      chromosome 6 at a region that has conserved synteny with human chromosome 2p11.2,
      and appears to express two transcripts in several mouse cell lines and adult
      tissues. On whole murine embryo blots Debt91 expresses primarily its small
      transcript and is differentially regulated during development. Analysis of
      expression in in vitro cell culture models suggests that Debt91 is an immediate
      early gene up-regulated during growth factor-induced branching tubulogenesis.

PMID- 12810065
TI  - Androgen-independent prostate cancer DU145 cells suppress androgen-dependent
      growth of prostate stromal cells through production of inhibitory factors for
      androgen responsiveness.
AB  - Imbalances in the epithelial-stromal interactions are important in the
      pathogenesis of prostate cancer. However, we know little about androgenic
      regulation in the stroma of prostate cancer. We examined the cancer-stromal
      interaction paying attention to androgen responsiveness of stromal side. In co
      culture, PC3 and LNCaP cells did not affect dihydrotestosterone (DHT)-dependent
      growth of prostate stromal cells (PrSCs), but DU145 cells significantly reduced
      it. Conditioned medium from DU145 cells (DU145-CM) also inhibited DHT-dependent
      PrSCs growth, androgen receptor (AR) expression, and prostate specific antigen
      transcription. Although the inhibitory effect of DU145-CM was not affected by
      neutralizing antibody against EGF, FGF-2, or TNF-alpha, pretreatment with
      testosterone-Sepharose partially reduced the inhibitory ability of DU145-CM.
      These results suggest that DU145 cells produce inhibitory factors for androgen
      responsiveness, including steroid-binding protein(s), and these may participate
      in crosstalk between DU145 cells and PrSCs as modulators of androgen.

PMID- 12810066
TI  - Identification of AMSH-LP containing a Jab1/MPN domain metalloenzyme motif.
AB  - We have isolated a cDNA clone encoding a new AMSH (associated molecule with the
      SH3 domain of STAM) family protein, termed AMSH-like protein (AMSH-LP). AMSH-LP
      has similar characteristics to AMSH; both AMSH-LP and AMSH are expressed
      ubiquitously in various human tissues, contain a putative nuclear localization
      signal (NLS), an Mpr/Pad1/N-terminal (MPN) domain, and a Jab1/MPN domain
      metalloenzyme (JAMM) motif in their structures, and are excluded from the nucleus
      when lacking either the NLS or MPN domain. Moreover, we observed an enhancement
      of interleukin 2 (IL-2)-mediated c-myc induction in AMSH-LP-transfected cells
      similar to that seen in AMSH-transfected cells, suggesting a functional
      similarity between AMSH-LP and AMSH. However, the present study demonstrated that
      AMSH-LP, unlike AMSH, fails to bind to the SH3 domains of STAM1 (signal
      transducing adaptor molecule 1) and Grb2. These results suggest that AMSH-LP and
      AMSH may have different functions.

PMID- 12810067
TI  - Expression of functional multidrug-resistance protein 1 in Saccharomyces
      cerevisiae: effects of N- and C-terminal affinity tags.
AB  - Studies of the multidrug-resistance protein 1 (MRP1) have been hampered by the
      lack of a simple expression system allowing for rapid generation of mutants and
      yielding milligram amounts of protein. Here, we describe a Saccharomyces
      cerevisiae expression system that meets those conditions. MRP1 was expressed
      under the control of the constitutive PMA1 (yeast proton pump) promoter. The best
      conditions for expression were determined, including the use of the chemical
      chaperone glycerol, which increased MRP1 expression. N-terminal poly-histidine or
      FLAG affinity tags reduce MRP1 expression, whereas the same tags fused to the C
      terminus had no effect. All the fusion proteins were functional. We conclude that
      because of its low cost and simplicity, the S. cerevisiae-based MRP1-expression
      system will be useful for studies where a large number of mutants or milligram
      amounts of purified MRP1 are needed.

PMID- 12810068
TI  - Control mechanisms in the regulation of telomerase reverse transcriptase
      expression in differentiating human teratocarcinoma cells.
AB  - Telomerase is active in about 90% of cancers and contributes to the immortality
      of cancer cells by maintaining the lengths of the ends of chromosomes.
      Undifferentiated embryonic human teratocarcinoma (HT) cells were found to express
      high levels of hTERT, the catalytic subunit of telomerase, and the hTERT promoter
      was unmethylated in these cells. Retinoic acid (RA)-induced differentiation led
      to hTERT gene silencing and increased methylation of the hTERT promoter.
      Treatment with trichostatin A, a histone deacetylase inhibitor, resulted in hTERT
      reactivation only in very early differentiating HT cells. After methylation
      patterns had been established within the hTERT promoter region in late
      differentiating cells, 5-azacytidine, a common demethylating agent, activated the
      hTERT gene but trichostatin A had no effect on hTERT transcription. These studies
      suggest that histone deacetylation is involved in early hTERT gene down
      regulation and that DNA methylation may maintain silencing of the hTERT gene in
      these cells.

PMID- 12810069
TI  - p54nrb acts as a transcriptional coactivator for activation function 1 of the
      human androgen receptor.
AB  - The androgen receptor (AR) has two transactivation functions that have been
      mapped to the N- and C-terminal domains and designated as activation function-1
      (AF-1) and AF-2, respectively. While the molecular basis for AF-2 function has
      been well studied, little is known about AF-1 coregulators. Therefore, we
      attempted to identify AF-1-interacting proteins from HEK293 cells by biochemical
      purification followed by mass fingerprinting by matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Purified AF-1 region
      interacting proteins were found to contain nuclear RNA-binding protein p54(nrb),
      polypyrimidine tract-binding protein-associated splicing factor (PSF),
      paraspeckle protein 1 (PSP1), and PSP2, which are assumed to be involved in pre
      mRNA processing. p54(nrb) interacted with AR via the A/B domain in a ligand
      dependent manner. Reflecting the physical interaction between p54(nrb) and the AR
      A/B domain, AR AF-1 function was potentiated by p54(nrb). Our results suggest
      that p54(nrb) functions as a coactivator of AR that potentiates transcription,
      and presumably splicing as well.

PMID- 12810070
TI  - Reconstitution of archaeal ribonuclease P from RNA and four protein components.
AB  - Ribonuclease P (RNase P) is an endonuclease responsible for generating the 5(')
      end of matured tRNA molecules. A homology search of the hyperthermophilic
      archaeon Pyrococcus horikoshii OT3 genome database revealed that the four genes,
      PH1481, PH1601, PH1771, and PH1877, have a significant homology to those encoding
      RNase P protein subunits, hpop5, Rpp21, Rpp29, and Rpp30, of human, respectively.
      These genes were expressed in Escherichia coli cells, and the resulting proteins
      Ph1481p, Ph1601p, Ph1771p, and Ph1877p were purified to apparent homogeneity in a
      set of column chromatographies. The four proteins were characterized in terms of
      their capability to bind the cognate RNase P RNA from P. horikoshii. All four
      proteins exhibited the binding activity to the RNase P RNA. In vitro
      reconstitution of four putative RNase P proteins with the in vitro transcripted
      P. horikoshii RNase P RNA revealed that three proteins Ph1481p, Ph1601p, and
      Ph1771p, and RNase P RNA are minimal components for the RNase P activity.
      However, addition of the fourth protein Ph1877p strongly stimulated enzymatic
      activity, indicating that all four proteins and RNase P RNA are essential for
      optimal RNase P activity. The present data will pave the way for the elucidation
      of the reaction mechanism for archaeal as well as eukaryotic RNase P.

PMID- 12810071
TI  - Down-regulation of Toll-like receptor expression in monocyte-derived Langerhans
      cell-like cells: implications of low-responsiveness to bacterial components in
      the epidermal Langerhans cells.
AB  - In the skin, there are unique dendritic cells called Langerhans cells, however,
      it remains unclear why this particular type of dendritic cell resides in the
      epidermis. Langerhans cell-like dendritic cells (LCs) can be generated from
      CD14(+) monocytes in the presence of GM-CSF, IL-4, and TGF-beta1. We compared LCs
      with monocyte-derived dendritic cells (DCs) generated from CD14(+) monocytes in
      the presence of GM-CSF and IL-4 and examined the effect of exposure to two
      distinct bacterial stimuli via Toll-like receptors (TLRs), such as peptidoglycan
      (PGN) and lipopolysaccharide (LPS) on LCs and DCs. Although stimulation with both
      ligands induced a marked up-regulation of CD83 expression on DCs, PGN but not LPS
      elicited up-regulation of expression CD83 on LCs. Consistent with these results,
      TLR2 and TLR4 were expressed on DCs, whereas only TLR2 was weakly detected on
      LCs. These findings suggest the actual feature of epidermal Langerhans cells with
      low-responsiveness to skin commensals.

PMID- 12810072
TI  - A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted
      areas of mouse brain.
AB  - A variety of secreted and membrane proteins play key roles in the formation of
      neuronal circuits in the central nervous system. Using the signal sequence trap
      method, we isolated and characterized a novel gene, Btcl1 (brain-specific
      transmembrane protein containing two CUB and an LDLa domains). BTCL1 has
      significant homology with neuropilin-1 and -2 in their CUB domains. Domain
      structure of BTCL1 indicates that BTCL1 belongs to a new class of brain-specific
      CUB domain-containing protein. On Northern blot analysis, Btcl1 mRNA was observed
      as a single transcript of 3.7 kb specifically in the brain. In situ hybridization
      analysis revealed that Btcl1 mRNA was highly expressed in the hippocampal CA3
      region, olfactory bulb, and neocortex in the adult brain. Expression pattern of
      mRNA and structural similarity with neuropilin suggest that BTCL1 plays a role in
      the development and/or maintenance of neuronal circuitry.

PMID- 12810073
TI  - Predominant expression of the short form of GGA3 in human cell lines and tissues.
AB  - Three GGAs (GGA1-3) were found in humans, among which GGA3 has short and long
      forms of spliced variants (GGA3-S and GGA3-L). The present study analyzed
      expression patterns of both GGA3 variants in human tissues and cell lines.
      Western blot analysis revealed that the brain contained both GGA3-S and -L, while
      other tissues and cell lines examined predominantly expressed GGA3-S. By double
      immunofluorescence microscopy, GGA1 and GGA3 were localized with slightly
      different patterns in both the trans-Golgi network (TGN) and peripheral region.
      When the dominant-negative mutant, VHS-GAT domain, of GGA1 or GGA3-L was
      overexpressed, TGN-associated GGA1 was redistributed into the cytoplasm. However,
      the GGA3 distribution was not affected by the expression of either VHS-GAT
      domain. These results indicate that GGA3-S which would not be directly involved
      in the cargo protein recognition is predominantly expressed in human tissues
      except the brain and in cell lines.

PMID- 12810075
TI  - Differential expressions of heme oxygenase-1 gene in CD25- and CD25+ subsets of
      human CD4+ T cells.
AB  - Growing evidence suggests that the immunomodulatory heme oxygenase-1 (HO-1) may
      have an important role in regulating T-cell responses. In this study, we
      investigated whether CD4(+)CD25(-) and CD4(+)CD25(+) T cells of human CD4(+)
      subpopulation could differentially express HO-1. Our results obtained from
      qualitative reverse transcriptase-polymerase chain reaction and quantitative flow
      cytometry analyses revealed that the CD4(+)CD25(+) T cells constitutively express
      HO-1 and that T cell stimulation with plate-bound anti-CD3 in combination with
      soluble anti-CD28 not only induced HO-1 gene expression in the CD4(+)CD25(-) T
      cells but also up-regulated HO-1 gene expression in the CD4(+)CD25(+) T cells.
      Our further studies showed that CD28 signal alone was enough to induce HO-1
      expression and CD3 signal, of which signal alone did not induce HO-1 expression,
      was required at least for full HO-1 expression in both CD25(-) and CD25(+)
      subsets of human CD4(+) T cells. In addition, transfection of human Jurkat T
      cells with HO-1 suppressed the cellular proliferation, and this effect was
      reversed by zinc protoporphyrin, a specific HO competitive inhibitor. Taken
      together, we have first reported that human CD4(+)CD25(+) regulatory T cells
      constitutively express HO-1 and that HO-1 inhibits Jurkat T cell proliferation.

PMID- 12810074
TI  - A fission yeast homologue of the human uracil-DNA-glycosylase and their roles in
      causing DNA damage after overexpression.
AB  - A functional homologue (ung1) of the human uracil-DNA-glycosylase (UNG) gene was
      characterized from fission yeast (Schizosaccharomyces pombe). The ung1 gene is
      highly conserved and encodes a protein with uracil-DNA-glycosylase activity
      similar to human UNG. The Ung1 protein localizes predominantly to the nucleus,
      suggesting that it is more similar to the nuclear form (UNG2) than the
      mitochondrial form (UNG1) of human UNG. Even though deletion of ung1 does not
      cause any obvious defects, overexpression of ung1 increases the mutation
      frequency. Overexpression of ung1 or human UNG2 induces a DNA checkpoint
      dependent cell cycle delay and causes cell death which is enhanced when the
      checkpoints are inactive. In addition, the steady-state level of AP
      (apurinic/apyrimidinic) sites increases after ung1 overexpression, indicating
      that AP sites are likely to be the DNA damage caused by overexpression. Analysis
      of mutant ung indicates that catalytic activity is not required for the effects
      of overexpression, but that binding of Ung1 or UNG2 to AP sites may be important.

PMID- 12810076
TI  - Formation of N-(hexanoyl)ethanolamine, a novel phosphatidylethanolamine adduct,
      during the oxidation of erythrocyte membrane and low-density lipoprotein.
AB  - The primary amino groups of biomolecules such as aminophospholipids, as well as
      proteins, are the potential targets of covalent modifications by lipid
      peroxidation products; however, little attention has been paid to the
      modification of aminophospholipids such as phosphatidylethanolamine (PE). The
      purpose of this study was to characterize the formation of a novel modified
      phospholipid, N-(hexanoyl)phosphatidylethanolamine (HEPE), in the reaction of PE
      with lipid hydroperoxides using mass spectrometric analyses. Upon reaction of egg
      PE with 13-hydroperoxyoctadecadienoic acid or other oxidized polyunsaturated
      fatty acids followed by phospholipase D-mediated hydrolysis, the formation of N
      (hexanoyl)ethanolamine (HEEA), a head group of HEPE, was confirmed by isotope
      dilution liquid chromatography/tandem mass spectrometry. Moreover, increasing
      HEEA was detected in the hydrolysates of oxidized erythrocyte ghosts and low
      density lipoprotein with their increasing lipid peroxidation levels.
      Collectively, these results suggest that the N-hexanoylated product of
      phospholipid, HEPE, can be generated during lipid peroxidation and may serve as
      one mechanism for the covalent modification of aminophospholipids in vivo.

PMID- 12810078
TI  - The human solute carrier SLC41A1 belongs to a novel eukaryotic subfamily with
      homology to prokaryotic MgtE Mg2+ transporters.
AB  - We report here the first identification and structural characterization of a
      eukaryotic protein with homology to the bacterial MgtE family of potential Mg(2+)
      transporters. This human protein, denoted solute carrier family 41 member 1
      (SLC41A1), consists of 513 amino acids with an estimated molecular weight of
      56kDa. Computer analysis of the protein structure reveals that the protein
      consists of 10 putative transmembrane domains and includes two distinct domains
      highly homologous to the integral membrane part of the bacterial MgtE protein
      family. The gene encoding SLC41A1 is found on chromosome 1 (1q31-32) and the
      protein coding sequence is found on 10 exons. A 5-kb long transcript is
      identified in various human tissues with highest expression levels in heart and
      testis. We have also identified 10 SLC41A1 homologs in Homo sapiens, Mus
      musculus, Drosophila melanogaster, Anopheles gambiae, and Caenorhabditis elegans,
      and propose that these hypothetical proteins belong to a novel eukaryotic gene
      family.

PMID- 12810077
TI  - Effective small interfering RNAs and phosphorothioate antisense DNAs have
      different preferences for target sites in the luciferase mRNAs.
AB  - Antisense DNA target sites can be selected by the accessibility of the mRNA
      target. It remains unknown whether a mRNA site that is accessible to an antisense
      DNA is also a good candidate target site for a siRNA. Here, we reported a
      parallel analysis of 12 pairs of antisense DNAs and siRNA duplexes for their
      potency to inhibit reporter luciferase activity in mammalian cells, both of the
      antisense DNA and siRNA agents in a pair being directed to same site in the mRNA.
      Five siRNAs and two antisense DNAs turned out to be effective, but the sites
      targeted by those effective siRNAs and antisense DNAs did not overlap. Our
      results indicated that effective antisense DNAs and siRNAs have different
      preferences for target sites in the mRNA.

PMID- 12810079
TI  - The two NK-1 binding sites are distinguished by one radiolabelled substance P
      analogue.
AB  - Two non-stoichiometric binding sites had previously been characterized for the NK
      1 receptor using two different types of radiolabelled analogues of substance P.
      However, the question remained on their eventual conformational interconversion
      induced or not by the ligand. In this study, kinetic, saturation, and competition
      studies using [3H]propionyl[Pro(9)]SP demonstrate the existence of two
      independent binding components in CHO cells transfected with the human NK-1
      receptor, with K(d) values of 0.040 nM ( approximately 20% of total sites) and
      5.9 nM ( approximately 80% of total sites) that correspond to those of the two
      previously described binding sites. These two binding sites do not seem to
      interconvert since the minor one can be selectively extinguished in saturation
      studies in the presence of a SP analogue specific of this binding site.

PMID- 12810080
TI  - p38 MAPK inhibition is critically involved in VEGFR-2-mediated endothelial cell
      survival.
AB  - Vascular endothelial growth factor (VEGF) promotes vasculogenesis,
      arteriogenesis, and angiogenesis by stimulating proliferation, migration, and
      cell survival of endothelial cells. VEGF mediates its actions through activation
      of two receptor tyrosine kinases, VEGFR-1 and VEGFR-2. Serum starvation led to
      apoptosis of human umbilical vein endothelial cells (HUVEC), which was
      accompanied by activation of p38 MAPK and caspase-3. Stimulation of both VEGF
      receptors resulted in a considerable decrease of apoptosis, which was associated
      with the inhibition of p38 MAPK and caspase-3 activity. Selective stimulation of
      VEGFR-2 showed similar results, whereas the isolated activation of VEGFR-1 was
      without effect. Incubation of HUVEC with SB203580, a p38 MAPK inhibitor, resulted
      in similar effects as VEGF-stimulation: p38 MAPK and caspase-3 enzyme activity
      were reduced and apoptosis was prevented. These data indicate that activation of
      VEGFR-2 prevents endothelial cell apoptosis by inhibiting p38 MAPK
      phosphorylation and thus, reducing caspase-3 activity.

PMID- 12810081
TI  - Ca2+ signal blockers can inhibit M/A transition in mammalian cells by interfering
      with the spindle checkpoint.
AB  - A key step in mitosis is the sister-chromatid separation at the metaphase
      anaphase (M/A) transition. Several earlier studies had suggested that Ca(2+)
      signal is involved in regulating this process in somatic cells. The detailed
      mechanisms, however, are not yet well understood. In this study, we used the GFP
      gene fusion method and a living-cell imaging technique to examine the effects of
      suppressing cytosolic Ca(2+) level on the mitotic process in HeLa and PtK2 cells.
      We observed that application of the Ca(2+) chelator BAPTA/AM can block or
      severely delay the M/A transition. This blockage was caused by a failure in
      activating the anaphase-promoting complex (APC), since both cyclin B and securin
      could not be degraded under this situation. Furthermore, using YFP-labeled
      tubulin, we found that the mitotic spindle structure in most of the BAPTA-treated
      cells gradually deformed with time. Other Ca(2+) signal blockers, such as
      heparin, also produced a similar effect. These results suggest that one pathway
      for the blockage of M/A transition by suppressing cytosolic Ca(2+) level is due
      to its interference with the mitotic spindle checkpoint.

PMID- 12810082
TI  - Fibronectin blocks p38 and jnk activation by cyclic strain in Caco-2 cells.
AB  - Diverse repetitive forces deform the intestinal epithelium and basement membrane.
      Such repetitive deformation induces intestinal epithelial proliferation,
      differentiation, and intracellular signaling. Although at least some deformation
      induced signals probably involve integrins, the matrix-dependence of these
      signals is poorly understood. We compared rapid strain activation of p38 and jnk
      in human Caco-2 intestinal epithelial cells cultured on collagen I, collagen IV,
      laminin, and tissue fibronectin. These signals were inhibited in cells on a
      fibronectin substrate, but activated by strain on collagens and laminin.
      Furthermore, adding 300 microg/ml plasma fibronectin (approximately the
      concentration found in plasma) to the culture medium inhibited strain activation
      of p38 and jnk in cells cultured on collagen. Since tissue and plasma fibronectin
      levels vary in acute or chronic inflammatory or infectious conditions, these
      results suggest that tissue or plasma fibronectin may modulate the intestinal
      epithelial response to repetitive deformation.

PMID- 12810083
TI  - pVHL-independent ubiquitination of HIF1alpha and its stabilization by cobalt ion.
AB  - Recent studies have shown that hypoxia-inducible factor1alpha (HIF1alpha) is
      ubiquitinated by an E3-ligase complex containing von Hippel-Lindau gene product
      (pVHL) after which it is targeted for proteasomal degradation. In this study, we
      showed that HIF1alpha was stabilized in the pVHL-deficient cell line 786-0
      treated with a proteasome inhibitor or Co(2+). This suggests that HIF1alpha is
      also ubiquitinated by a pVHL-independent pathway and that its stability is
      regulated by Co(2+). Indeed, using the COS cell expression system, we confirmed
      that HIF1alpha is ubiquitinated at the N-terminal region by a pVHL-independent
      pathway and that its degradation is inhibited by Co(2+). We also demonstrated
      that Co(2+) binds to both PAS domains in the N-terminal region of HIF1alpha.
      These observations imply that the stability of HIF1alpha is regulated by an
      additional pathway through the cobalt binding of PAS domains.

PMID- 12810084
TI  - Establishment of a hepatitis C virus subgenomic replicon derived from human
      hepatocytes infected in vitro.
AB  - The hepatitis C virus (HCV) replicon system is a potent tool for understanding
      the mechanisms of HCV replication and proliferation, and for the development of
      treatments for patients with HCV. Recently, we established an HCV subgenomic
      replicon (50-1) using HCV genome RNA obtained from the cultured human T cell line
      MT-2C infected with HCV (isolate 1B-1) in vitro. In order to further obtain other
      HCV replicons without difficulty, we generated a replicon RNA library derived
      from human non-neoplastic hepatocytes infected with HCV (isolate 1B-2) in vitro.
      Upon transfection of the generated RNA library to "cured cells," from which the
      50-1 subgenomic replicon was eliminated by prolonged treatment with interferon
      alpha, we successfully established a new HCV subgenomic replicon, 1B-2R1. We
      characterized 1B-2R1 replicon in terms of efficiency of replication, HCV
      sequence, and sensitivity to interferons. The results revealed that the
      replication level of the 1B-2R1 replicon was comparable to that of the 50-1
      replicon. We also found that the 1B-2R1 replicon possessed an HCV sequence
      distinct from those of other replicons established to date, and that the 1B-2R1
      replicon was sensitive to interferon-alpha, interferon-beta, and interferon
      gamma. Taken together, present results indicate that the replicon RNA library
      generated using an in vitro HCV infection system is useful for the establishment
      of an HCV subgenomic replicon.

PMID- 12810085
TI  - Regulation of FcepsilonRI-mediated signaling by an adaptor protein STAP-2/BSK in
      rat basophilic leukemia RBL-2H3 cells.
AB  - Crosslinking of multivalent antigen bound IgE transduces FcepsilonRI mediated
      signaling cascades, which activate nonreceptor-type protein-tyrosine kinases and
      subsequent tyrosine phosphorylation of cellular proteins, and these are critical
      elements for degranulation in mast cells. We cloned a novel adaptor molecule,
      signal transducing adaptor protein (STAP)-2 containing PH and SH2-like domains as
      a c-fms interacting protein. STAP-2 was identical to a recently cloned adaptor
      molecule, BKS, a substrate of BRK (breast tumor kinase) tyrosine kinase, although
      its function is still unknown. To examine a novel function of STAP-2/BSK, we
      expressed STAP-2/BSK or its mutants in rat basophilic leukemia RBL-2H3 cells.
      Overexpression of STAP-2/BSK resulted in a suppression of FcepsilonRI-mediated
      calcium mobilization and degranulation. FcepsilonRI-induced tyrosine
      phosphorylation of phospholipase C-gamma (PLC-gamma) but not Syk was
      significantly suppressed in these cells. Furthermore, STAP-2/BSK associated with
      PLC-gamma in vivo. These data indicate that STAP-2/BSK negatively controls the
      FcepsilonRI-mediated calcium mobilization and degranulation by direct modulation
      of tyrosine phosphorylation of PLC-gamma.

PMID- 12810086
TI  - Chemical complementation: small-molecule-based genetic selection in yeast.
AB  - Protein and metabolic engineering would greatly benefit from a general system
      linking the presence of a small molecule to the power of genetic selection. We
      use nuclear receptors to link the survival of Saccharomyces cerevisiae to the
      presence of small molecules through genetic selection, extending classical
      genetic complementation to a new "chemical complementation." In this system the
      Gal4 DNA-binding domain is fused to ligand-binding domains from two nuclear
      receptors, expressed in the strain PJ69-4A, and grown on plates containing known
      ligands for the receptors. Yeast survive on selective plates only in the presence
      of a nuclear receptor and the corresponding ligand. Mutagenesis can increase the
      sensitivity of chemical complementation. This system may be extended to engineer
      nuclear receptors for practically any small molecule through directed evolution
      coupled to genetic selection, and for performing metabolic engineering in yeast.

PMID- 12810087
TI  - Effect of phosphodiesterase type 4 on circadian clock gene Per1 transcription.
AB  - The induction of Per1 gene in the suprachiasmatic nucleus, the center of the
      circadian clock, is assumed to play significant roles in the adjustment of the
      internal clock. cAMP is one of the intracellular mediators which activates Per1
      transcription. Here, we showed that the amount of the rat Per1 (rPer1) transcript
      induced by forskolin (FK) was significantly upregulated by the inhibition of
      phosphodiesterase type 4 (PDE4), a specific phosphodiesterase for cAMP, in rat-1
      fibroblasts. Administration of rolipram, a specific inhibitor of PDE4, increased
      intracellular cAMP concentration, phosphorylation of cAMP response element
      binding protein (CREB) and enhanced rPer1 induction at their peaks. However, in
      the falling phase of rPer1 induction, the inhibition of PDE4 hardly affected the
      profile of rPer1 expression. These findings suggest the involvement of PDE4 for
      the regulation of rPer1 expression via cAMP metabolism at peak of the induction
      but little or no participation of PDE4 in the decreasing phase of the gene
      expression.

PMID- 12810090
TI  - Impacts of the Jessica oil spill: an introduction.

PMID- 12810088
TI  - Influence of tat mutations on the ribose-binding protein translocation in
      Escherichia coli.
AB  - Proteins are exported across the bacterial cytoplasmic membrane either as
      unfolded precursors via the Sec machinery or in folded conformation via the Tat
      system. The ribose-binding protein (RBP) of Escherichia coli is a Sec-pathway
      substrate. Intriguingly, it exhibits fast folding kinetics and its export is
      independent of SecB, a general chaperone protein dedicated for protein secretion.
      In this study, we found that the quantity of RBP was significantly reduced in the
      periplasm of tat mutants, which was restored by in trans expression of the tatABC
      genes. Pulse-chase experiments showed that significant amount of wild-type RBP
      was processed in a secY mutant in the presence of azide (SecA inhibitor), whereas
      the processing of a slow folding RBP derivative was almost completely blocked
      under the same conditions. These results would suggest that under the Sec
      defective conditions the export of a portion of folded RBP could be rescued by
      the Tat system.

PMID- 12810089
TI  - Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine
      H3-receptors.
AB  - We had previously reported that activation of histamine H(3)-receptors (H(3)R) on
      cardiac adrenergic nerve terminals decreases norepinephrine (NE) overflow from
      ischemic hearts and alleviates reperfusion arrhythmias. Thus, we used transgenic
      mice lacking H(3)R (H(3)R(-/-)) to investigate whether ischemic arrhythmias might
      be more severe in H(3)R(-/-) hearts than in hearts with intact H(3)R
      (H(3)R(+/+)). We report a greater incidence and longer duration of ventricular
      fibrillation (VF) in H(3)R(-/-) hearts subjected to ischemia. VF duration was
      linearly correlated with NE overflow, suggesting a possible cause-effect
      relationship between magnitude of NE release and severity of reperfusion
      arrhythmias. Thus, our findings strengthen a protective antiarrhythmic role of
      H(3)R in myocardial ischemia. Since malignant tachyarrhythmias cause sudden death
      in ischemic heart disease, attenuation of NE release by selective H(3)R agonists
      may represent a new approach in the prevention and treatment of ischemic
      arrhythmias.

PMID- 12810091
TI  - Impacts of the Jessica oil spill on intertidal and shallow subtidal plants and
      animals.
AB  - Densities of fishes, invertebrates and plants at rocky intertidal and shallow
      subtidal sites were censused 1-2 days prior to the Jessica oil spill and compared
      with information obtained for the same sites one month after the spill, both for
      sites impacted by oil and unaffected reference sites. While the availability of
      pre-spill data made this analysis one of the most powerful to date for testing
      impacts of oil on shoreline environments, no clear changes attributable to oiling
      could be identified. Discharged oil appeared to cause very little impact in the
      intertidal and shallow subtidal zones, with such impacts lying within the range
      of natural spatial and temporal variation at sites investigated. Factors
      considered to minimize impact in Galapagos included paucity of fully sheltered
      shores in spill path, moderate wave action, warm temperature, high levels of
      sunlight, and mixing of bunker oil with diesel.

PMID- 12810092
TI  - The effect of the Jessica grounding on subtidal invertebrate and plant
      communities at the Galapagos wreck site.
AB  - Impacts of the grounding of the oil tanker Jessica off San Cristobal island,
      Galapagos, included both effects of oil on biota and also mechanical effects
      associated with a shallow furrow 50 m x 30 m gouged across the rocky seafloor and
      wreckage strewn over 7500 m(2). The wreckage represented a minor but potentially
      chronic source of pollution to the surrounding environment through delayed
      releases of oil, antifouling compounds and other toxic chemicals, and a possible
      source of exotic marine taxa. Investigation at the wreck site indicated that
      impacts on subtidal plant and macro-invertebrate communities were largely
      confined within 100 m of the wreck site itself. Observed population effects
      included significant increases in cover of opportunistic algae (filamentous green
      algae, filamentous red algae and Ulva sp.) and the hydroid Ectopleura media
      adjacent to the wreck, while densities of the green sea urchin Lytechinus
      semituberculatus significantly decreased from 0.3 m(-2) adjacent to the wreck to
      11 m(-2) at 100 m distance.

PMID- 12810093
TI  - The effect of the Jessica grounding on Galapagos reef fish communities adjacent
      to the wreck site.
AB  - The grounding of the oil tanker Jessica off San Cristobal Island, Galapagos,
      resulted in generally elevated rather than depressed densities of fishes adjacent
      to the wreck site 15 weeks post spill. Species richness of fishes declined along
      transects out from the wreck; however, patterns were inconsistent for different
      depth strata, with the most clearly defined decline evident for the intermediate
      5-7 m depth stratum. Fish species attracted to the immediate wreck site, most
      notably the surgeonfish Prionurus laticlavius, the damselfish Microspathodon
      dorsalis and the angelfish Holacanthus passer, were considered to be responding
      either to the heterogeneity provided by the wreck structure or elevated densities
      of macroalgae. The fish community at the wreck site lay outside the range of
      variation for other sites investigated in the region; however, contrary to
      predictions of grounding impacts, the fish assemblage immediately adjacent to the
      wreckage showed greater faunal similarity to reference sites than did fish
      assemblage at 60-90 m distance from the grounding.

PMID- 12810094
TI  - Oil contamination of sedimentary shores of the Galapagos Islands following the
      wreck of the Jessica.
AB  - Sediment samples were collected from sandy beaches at a variety of sites in the
      southern Galapagos Archipelago to assess levels of hydrocarbon contamination
      following the wreck of the oil tanker Jessica. Hydrocarbon levels in sediments
      were generally very low by international standards ranging between 0.4 and 48.9
      ppm, with contamination attributable to the Jessica only detected at three sites
      Santa Fe, Playa Estacion (Puerto Ayora, Santa Cruz) and Long Beach (Isabela).
      There was evidence of residual hydrocarbon contamination from sources other than
      the wreck of the Jessica.

PMID- 12810095
TI  - Impacts of the Jessica oil spill on sea lion (Zalophus wollebaeki) populations.
AB  - Following the Jessica oil spill, a total of 79 oiled Galapagos sea lions
      (Zalophus wollebaeki) were recorded around the islands of San Cristobal, Santa
      Fe, Isabela and Floreana. Almost half of these animals required washing and other
      treatment. One sea lion death and a high incidence of conjunctivitis and burns
      were detected during the period of the oil spill. Sea lion populations exhibited
      a tendency for decline in the first months following the spill at all three
      colonies monitored close to the grounding site on San Cristobal. By comparison,
      declines of similar magnitude occurred at only one of six sea lion colonies
      monitored on islands more distant from the spill. However, no significant
      decreases in population numbers were detected for any colony in the year
      following the spill. Galapagos sea lion populations were partially recovering
      from the much more catastrophic impact of the 1997/98 El Nino.

PMID- 12810096
TI  - Effects of the Jessica oil spill on artisanal fisheries in the Galapagos.
AB  - In contrast to local perceptions, the impact on the local Galapagos artisanal
      fishery of the 16 January 2001 grounding of the Jessica and subsequent oil spill
      was relatively minor. No significant changes in fishing effort, total fishing
      catches or catch-per-unit effort were detected after the spill based on analyses
      of fisheries monitoring data. Nevertheless, large boats tended to move away from
      sites near the path of the spill following the grounding in 2001, with no fishing
      recorded from the oil-affected regions of Floreana and southern Isabela in
      February 2001. The total fishing effort of small boats operating from the Jessica
      grounding island of San Cristobal also declined immediately after the spill,
      probably in part because such boats were used in clean up operations. During
      2001, prices paid to fishers remained stable at levels higher than in 2000, with
      the notable anomaly that prices fell precipitously to 30% of previous levels
      during a 1-2 week period in early February 2001. Fish exports remained at similar
      levels for the years 2000 and 2001; however, as in the previous year, little fish
      product was exported from Galapagos in the month following the spill, with most
      fish product dried and stored for up to two months prior to transport to the
      continent.

PMID- 12810097
TI  - SeaWiFS satellite monitoring of oil spill impact on primary production in the
      Galapagos Marine Reserve.
AB  - Near daily satellite monitoring of ocean colour using sea viewing wide angle of
      field viewing sensor (SeaWiFS) allowed the oceanic and near coastal chlorophyll-a
      distributions to be followed across the Galapagos Marine Reserve (GMR) from
      space. In the aftermath of the Jessica spill early indications suggested that,
      compared to the three preceding years 1998-2000, local chlorophyll concentrations
      over January 2001 were elevated across the Galapagos Marine Reserve [Biological
      Impacts of the Jessica Oil Spill on the Galapagos Environment: Preliminary
      Report. Charles Darwin Foundation, Puerto Ayora, Galapagos, Ecuador, 2001]. At
      the time of the spill the central and eastern extent of the archipelago was
      experiencing a spatially extensive moderate bloom event (0.5-2.5 mgm(-3) chl-a)
      extending over the central islands, including the source of the spill and areas
      of known impact such as the islands of Santa Fe, eastern Santa Cruz and Floreana
      directly in the advection path.Further investigation shows that chlorophyll
      across the affected regions of western San Cristobal, Santa Fe, southeast Santa
      Cruz, eastern Floreana and eastern Isabela declined in the week directly
      following the spill event, yet rose in the successive month to levels analogous
      to preceding years. Although there may have been a localised effect of the spill
      upon near coast phytoplankton primary production in the short term, the observed
      variance in the weeks following the spill was not significant in comparison to
      the normal high variation between years and within the El Nino/Southern
      Oscillation signal.

PMID- 12810098
TI  - The Toll-IL-1 receptor adaptor family grows to five members.
AB  - Toll-like receptor (TLR) signal transduction is mediated by an adaptor protein
      termed MyD88. In the case of TLR2 and TLR4, another adaptor related to MyD88
      called Mal also participates in signalling. Two recent papers have added a third
      adaptor to the family, called Toll-interleukin-1 receptor (TIR) domain-containing
      adaptor inducing interferon-beta (IFN-beta) (TRIF) or TIR-containing adaptor
      molecule-1 (TICAM-1), which is particularly important for IFN regulatory factor-3
      (IRF-3) activation by antiviral TLR3. Two additional adaptors are present in
      humans, termed Trif-related adaptor molecule (TRAM) and sterile alpha and HEAT
      Armadillo motifs (SARM). It is probable that differential use of adaptors will
      help explain the distinct pathways activated by TLRs during host defence.

PMID- 12810099
TI  - Immune responsiveness, tolerance and dsRNA: implications for traditional
      paradigms.
AB  - Double-stranded (ds)RNA motifs are central to immune regulation and block
      tolerance to tumor-associated, self- and foreign antigens. In addition, they
      could explain why DNA vectors encoding self-replicating mRNA (replicons) are more
      immunogenic than conventional DNA vaccines. Accumulating evidence on the
      immunomodulatory roles of dsRNAs warrants a reconsideration of various models of
      immune homeostasis.

PMID- 12810100
TI  - Research on complement: old issues revisited and a novel sphere of influence.
AB  - Immunology in recent years has taken a somewhat surprising turn, expressed by a
      renewed interest in innate immunity. Especially intriguing is the regulatory role
      exerted by the innate components on the adaptive response, with Toll receptors
      and complement components being the most investigated. This function has been
      firmly established for complement protein CR2 (CD21) as part of the BCR co
      receptor CD19/CD21/CD81. New findings are now providing a broader picture of
      complement and its tuning of the immune response; for example, complement
      proteins have been implicated in the control of T-cell-mediated responses. We
      will review some of these data here and summarize new discoveries in areas of
      research on more traditional topics within the complement literature, such as
      complement and renal diseases, and the therapeutic use of C1-Inhibitor. We cover
      papers selected from studies presented at the XIX International Complement
      Workshop, held in Palermo in September 2002, and published within the past six
      months.

PMID- 12810101
TI  - New jobs for an old enzyme: the revival of IDO.

PMID- 12810103
TI  - IL-6, monocyte infiltration and parenchymal cells.

PMID- 12810105
TI  - L-arginine metabolism in myeloid cells controls T-lymphocyte functions.
AB  - Although current attention has focused on regulatory T lymphocytes as suppressors
      of autoimmune responses, powerful immunosuppression is also mediated by a subset
      of myeloid cells that enter the lymphoid organs and peripheral tissues during
      times of immune stress. If these myeloid suppressor cells (MSCs) receive signals
      from activated T lymphocytes in the lymphoid organs, they block T-cell
      proliferation. MSCs use two enzymes involved in arginine metabolism to control T
      cell responses: inducible nitric oxide synthase (NOS2), which generates nitric
      oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1
      cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either
      enzyme alone results in a reversible block in T-cell proliferation. When both
      enzymes are induced together, peroxynitrites, generated by NOS2 under conditions
      of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus,
      NOS2 and Arg1 might act separately or synergistically in vivo to control specific
      types of T-cell responses, and selective antagonists of these enzymes might prove
      beneficial in fighting diseases in which T-cell responses are inappropriately
      suppressed. This Opinion is the second in a series on the regulation of the
      immune system by metabolic pathways.

PMID- 12810106
TI  - Molecular evolution of CXC chemokines: extant CXC chemokines originate from the
      CNS.
AB  - The mammalian CXC chemokine system comprises 16 ligands and six receptors, and
      its actions stretch well beyond the immune system. Recent elucidation of the
      pufferfish genome, a representative of an evolutionary ancient vertebrate class,
      has enabled analysis of the mammalian CXC chemokine system in a phylogenetic
      context. Comparison of the phylogenies of vertebrate CXC chemokines revealed that
      fish and mammals have found different solutions to similar problems, grafted on
      the same basic structural motif. Phylogenetic analyses showed that the large,
      highly redundant CXC chemokine family is a very recent phenomenon that is
      exclusive to higher vertebrates. Moreover, its ancestral role is found within the
      central nervous system and not within the immune system.

PMID- 12810107
TI  - What's the difference between CD80 and CD86?
AB  - CD28 and CD152 have crucial yet opposing functions in T-cell stimulation, in
      which CD28 promotes but CD152 inhibits T-cell responses. Intriguingly, they share
      two ligands, CD80 and CD86, but at present there is no clear model for
      understanding whether a ligand will promote or inhibit responses. Current
      perceptions are based around the concept that CD86 is the initial co-stimulatory
      ligand based on its more abundant and earlier expression pattern; CD80 has a role
      following antigen-presenting-cell activation. We describe an alternative view in
      which CD80 is the initial ligand, responsible for maintaining aspects of immune
      tolerance through interactions with CD152. These inhibitory functions can then be
      over-ridden by the upregulation of CD86 on dendritic cells as a result of
      inflammatory stimuli, leading to immune activation.

PMID- 12810108
TI  - From rafts to crafts: membrane asymmetry in moving cells.
AB  - Many important biological events, including the leukocyte-mediated immune
      response, wound repair, axon guidance and developmental patterning, involve
      persistent cell movement towards a directional signal, a process termed
      chemotaxis. Establishment of functional and spatial cell polarity is an absolute
      requirement for this response. We propose that redistribution of specific
      membrane microdomains, termed rafts, during cell migration is a pivotal step in
      achieving polarity. On the one hand, partitioning of molecules into rafts might
      help to localize proteins at the front or the rear of moving cells, and on the
      other hand, rafts might function as platforms for local activation and
      coordination of the signaling pathways involved in cell migration.

PMID- 12810109
TI  - Leukocyte-endothelial-cell interactions in leukocyte transmigration and the
      inflammatory response.
AB  - Both the innate and adaptive immune responses are dependent on the migration of
      leukocytes across endothelial cells. The process of diapedesis, in which the
      leukocyte crawls between tightly apposed endothelial cells, is a unique and
      complex process. Several molecules concentrated at the junctions of endothelial
      cells, originally described as having a role in holding the endothelial monolayer
      together, have also been shown to have a role in the emigration of leukocytes.
      Several mechanisms have been proposed for 'loosening' the junctions between
      endothelial cells to enable leukocyte passage. These leukocyte-endothelial-cell
      adhesion molecules are probably involved in regulating the signaling as well as
      the adhesion events of diapedesis. In addition, this Review introduces a new and
      unified nomenclature for the junctional adhesion molecule (JAM) family.

PMID- 12810110
TI  - Tumors as elusive targets of T-cell-based active immunotherapy.
AB  - The understanding of tumor-host interactions remains elusive despite significant
      progress in the identification of tumor antigens (TAs) recognized by autologous T
      cells. In particular, most human tumors do not regress and continue to grow in
      spite of spontaneous or immunization-induced immune responses demonstrated in
      circulating lymphocytes. Indeed, systemic immune responses might insufficiently
      address the complexity of tumor-host interactions because of factors, such as (1)
      the lack of productive T-cell receptor (TCR) engagement with epitope owing to
      qualitative and/or quantitative defects in the generation and maintenance of the
      immune response, (2) insufficient costimulation provided by the host, (3) the
      lack of localization of the immune response in target tissues and (4) the
      complexity of tumor-host interactions within the tumor microenvironment caused by
      temporal changes in tumor phenotypes and an array of immune mediators expressed
      in the tumor microenvironment. Here, we will review current knowledge of the
      different 'levels' of immune response that might be necessary for immunotherapy
      to be effective in the treatment of cancer. Furthermore, we will discuss the
      information still required in order to understand the mechanism(s) governing
      tumor rejection by the immune system in response to TA-specific immunization.

PMID- 12810112
TI  - The Heidelberg Conference: Setting an agenda for the IMIA working group on Health
      Information Systems.

PMID- 12810111
TI  - Transitional B cells: step by step towards immune competence.
AB  - Transitional B cells mark the crucial link between bone-marrow (BM) immature and
      peripheral mature B cells. Examination reveals unexpected heterogeneity,
      consisting of contiguous subsets with phenotypic and functional differences. Data
      point to the late transitional B-cell stage as a crucial juncture at which
      developing B cells gain access to splenic follicles, become responsive to T-cell
      help and lose sensitivity to negative selection, characterizing the immature B
      cell response to B-cell antigen receptor (BCR) signaling in vitro and in vivo.
      The biological and molecular processes directing maturation through this stage
      are becoming clearer through biochemical studies and murine models deficient in
      various components of the BCR signaling pathway.

PMID- 12810113
TI  - Hospital information systems: perspectives on problems and prospects, 1979 and
      2002.
AB  - PURPOSE: To assess progress made in hospital information systems (HIS) since
      1979, when the forerunner of the International Medical Informatics Association
      Working Group on HIS first met. METHODS: A review of the recommendations made in
      1979 identified core concerns, which were analyzed in light of the state of the
      art in 2002. RESULTS: Despite significant changes over the years, the underlying
      concerns identified in 1979 are still valid today. In 2002 as in 1979, HIS must
      be integrated into the hospital's organizational structure; financial and
      economic benefits depend upon using technology as an enabler of improved clinical
      outcomes; and education and training remain critical to the successful use of
      technology solutions. The tools available for addressing these concerns have
      changed enormously. Where there were dumb terminals, there are the World Wide Web
      and handheld devices. As a result, we are raising our expectations and changing
      the terms of our discussions. Today the focus is shifting to patient safety,
      decision support, and evidence-based practice; the concerns voiced in 1979 have
      become medical informatics cornerstones. New tools and new approaches now
      available can improve the quality of care. Using them appropriately requires
      careful planning and education for patients as well as healthcare professionals.

PMID- 12810114
TI  - Views on HIS development; recommendations of earlier working conferences compared
      with present challenges.
AB  - The objective of this paper is to consider the recommendations and expectations
      of the IMIA WG10 working conferences at Nijmegen (1988) and Gottingen (1991) from
      the present perspective. The methods: the original task description of WG10 is
      considered and the main items during the Nijmegen and Gottingen working
      conferences are addressed. The design and use of a HIS are compared by those for
      a ship. THE RESULTS: the tasks of WG10 have only partially been completed.
      However, for several items significant progress has been made. The conclusions:
      the recommendations of the earlier conferences are to a large extent still valid.
      A scientific foundation for HIS development has not yet been created, in this
      respect HIS design and development compares unfavourably with shipbuilding. The
      choice has to be made: either we consider HIS development as an art or we give
      priority to the development of a Science of Health Information Processing (SHIP)
      to found the HIS development.

PMID- 12810115
TI  - Making the boundaries clearer: revisiting information systems with fading
      boundaries.
AB  - PURPOSE: To address issues of importance in 1994 and what has happened in those
      issues. METHODS: A number of questions and issues will be examined. Were we right
      in our focus at that time and what did we miss? What has happened that perhaps
      changed our perspectives and philosophies? Has the need changed? Is the model of
      fading boundaries a correct one, and how far have we gone in realizing a
      communication system in dealing with those boundaries? What progress have we made
      internationally on these issues? How are we working internationally to solve
      these problems? RESULTS: The fifth working conference relating to hospital
      information systems (HIS) was held in Durham, North Carolina in August 1994. The
      Institute of Medicine publication The Computer-based Patient Record: An Essential
      Technology for Health Care had been published in 1991 and had begun influencing
      thinking and direction for clinical information systems. The difference between
      and relationship of HIS and Computer-based Patients Records was the topic of much
      discussion and debate. The 1994 conference strongly recognized the need for
      standards specifically for data exchange, unique patient identifier, data
      definitions and common clinical data sets and for clinical terminology.
      Interconnectivity and interoperability were identified as separate but related
      problems to be solved. Technology was not considered to be a barrier, and
      projections for bandwidth to meet data dissemination requirements were favorable.
      In the 7 years after the Durham conference, many things have changed
      dramatically. Progress has been made in a number of areas, and some of the
      projections have been realized. However, it is surprising to note what areas
      still remain problems, particularly noting what problems have been worked on
      without success and what problems have not even been addressed. It is interesting
      to speculate that if the Durham conference was repeated today, would it be
      accepted as a current event?

PMID- 12810116
TI  - Health information systems challenges: the Heidelberg conference and the future.
AB  - OBJECTIVES: To present a summary of the state of the art in Health Information
      Systems (HIS), as discussed during the Heidelberg HIS Working Group Conference,
      and to examine possible strategies for continuous improvement of the field.
      METHODS: The state of the art in HIS is briefly described, and the historical
      trends are examined that emerge from a review of the previous HIS Working Group
      conferences. To extrapolate from those trends and suggest possible new
      directions, we consider whether perceived difficulties in the diffusion of HIS
      systems are simply a product of technological factors, or whether fundamental
      social factors have been ignored. RESULTS: The experience with HIS environments
      is 'reasonably good' but not excellent, and true HIS success stories are not
      common. One of the apparent difficulties is that the typical HIS does not regard
      communication among clinical users as its core mission, even though repeated
      studies of information needs and practice patterns show that communication is the
      leading cost in today's health care environment. It is suggested that progress in
      the HIS arena will benefit from increased emphasis on the social aspects of
      health care, and better integration of diverse data to promote the organizational
      communication and workflow. Improvements could also come from a change to a
      highly participatory and evolutionary software engineering process, focusing on
      communication behavior and co-operative work practices. CONCLUSIONS: Future HIS
      development should view provider-provider and provider-patient communication as a
      core function, and incorporate features such as seamless support and tracking of
      communication, automatic gathering and presentation of data from multiple
      sources, data collection in atomic units by the most qualified provider, and
      integrated management, resource utilization, and tracking. The steps towards HIS
      that support these features might be smaller than generally suspected, once the
      appropriate changes in the reference point have been made.

PMID- 12810117
TI  - The HEGP component-based clinical information system.
AB  - OBJECTIVES: The opening of the Georges Pompidou University Hospital (HEGP) in
      southwest Paris from the merging of three aging facilities was the opportunity to
      conceive and deploy a brand new clinical information system (CIS) based on a
      component-based approach. This paper describes the process of selection of the
      business components, the main functions currently in use, and the technical
      infrastructure that proved necessary. METHODS: The HEGP CIS features generic and
      healthcare-related components. The generic components include a reference
      manager, a security manager, a document manager, a Corba bus, and various
      mediation and supervision tools. The healthcare-related components include the
      patient, healthcare record, act management, and resource scheduler components.
      RESULTS: Major functions of CIS were operational at the opening of the hospital
      in July 2000. Two years later, the unique patient record and the provider order
      entry system were used in 96% of the concerned healthcare units. Sixty-five
      percent of the biological orders and 55% of the imaging orders were directly
      entered by the physicians. Access to investigation results including on-line
      availability of images is used by physicians in 100% of the units. DISCUSSION AND
      CONCLUSION: A component-based approach was found to be high-performing and cost
      effective for the design and deployment of HEGP CIS.

PMID- 12810118
TI  - Building man-man-machine synergies: experiences from the Vanderbilt and Geneva
      clinical information systems.
AB  - OBJECTIVES: To demonstrate how a transition to an open hospital information
      system architecture can help foster stronger collaborations between computer
      based clinical tools and the network of care process stakeholders. METHODS:
      Description of two evolution strategies towards an open, component-based
      architecture: the vertical decomposition of a monolithic system, and the
      transversal integration of foundation components such as terminology servers,
      documentation management, prescription, scheduling, workflow and notification
      engines. CONCLUSION: The progressive migration of production clinical systems
      towards a component-based architecture is feasible at a reasonable cost and leads
      to substantial benefits in terms of user acceptance through participative design
      and collaborative maintenance of knowledge bases, as well as improved ability to
      evolve, scale and share individual components. A taxonomy of the components of a
      health information system and their interactions should be developed to realize
      the collaborative potential of a marketplace of interoperable components.

PMID- 12810119
TI  - VistA--U.S. Department of Veterans Affairs national-scale HIS.
AB  - The Veterans Health Administration of the U.S. Department of Veterans Affairs has
      a long, successful, and interesting history of using information technology to
      meet its mission. Each medical center is computerized to a degree that surprises
      the uninitiated. For example, medical documentation and ordering are computerized
      at every facility. A sophisticated national infrastructure has been developed to
      replicate, support, and evolve single-center successes. With advances in inter
      facility networking, data sharing, and specialized central support and technical
      tools, VistA is becoming a single, highly scalable national health information
      system (HIS) solution. In this paper, we present an historical overview of
      VistA's development, describe its current functionality, and discuss its
      emergence as a national-scale hospital information system.

PMID- 12810120
TI  - Standards for detailed clinical models as the basis for medical data exchange and
      decision support.
AB  - INTRODUCTION: Detailed clinical models are necessary to exchange medical data
      between heterogeneous computer systems and to maintain consistency in a
      longitudinal electronic medical record system. At Intermountain Health Care
      (IHC), we have a history of designing detailed clinical models. The purpose of
      this paper is to share our experience and the lessons we have learned over the
      last 5 years. DESIGN: IHC's newest model is implemented using eXtensible Markup
      Language (XML) Schema as the formalism, and conforms to the Health Level Seven
      (HL7) version 3 data types. The centerpiece of the new strategy is the Clinical
      Event Model, which is a flexible name-value pair data structure that is tightly
      linked to a coded terminology. DISCUSSION: We describe IHC's third-generation
      strategy for representing and implementing detailed clinical models, and discuss
      the reasons for this design.

PMID- 12810121
TI  - Open Source software in medical informatics--why, how and what.
AB  - 'Open Source' is a 20-40 year old approach to licensing and distributing software
      that has recently burst into public view. Against conventional wisdom this
      approach has been wildly successful in the general software market--probably
      because the openness lets programmers the world over obtain, critique, use, and
      build upon the source code without licensing fees. Linux, a UNIX-like operating
      system, is the best known success. But computer scientists at the University of
      California, Berkeley began the tradition of software sharing in the mid 1970s
      with BSD UNIX and distributed the major internet network protocols as source code
      without a fee. Medical informatics has its own history of Open Source
      distribution: Massachusetts General's COSTAR and the Veterans Administration's
      VISTA software have been distributed as source code at no cost for decades.
      Bioinformatics, our sister field, has embraced the Open Source movement and
      developed rich libraries of open-source software. Open Source has now gained a
      tiny foothold in health care (OSCAR GEHR, OpenEMed). Medical informatics
      researchers and funding agencies should support and nurture this movement. In a
      world where open-source modules were integrated into operational health care
      systems, informatics researchers would have real world niches into which they
      could engraft and test their software inventions. This could produce a burst of
      innovation that would help solve the many problems of the health care system. We
      at the Regenstrief Institute are doing our part by moving all of our development
      to the open-source model.

PMID- 12810122
TI  - The collaborative edge: patient empowerment for vulnerable populations.
AB  - OBJECTIVE: The problems with access to care and the special needs for educational
      outreach for disadvantage or vulnerable populations of patients require
      innovation. This paper describes Baby CareLink use of information technology to
      support communication, consultation, and collaboration among colleagues as well
      as with patients, their families, and community resources. METHODS: In response
      to the educational, emotional and communication needs of parents of premature
      infants and the clinicians who care for the infants and support the families, we
      developed Baby CareLink, a secure collaborative environment. Baby CareLink
      provides a nurturing environment where parents, even though remote from the
      Neonatal Intensive Care Unit, can actively participate in decisions surrounding
      their baby's care. RESULTS: In a southeastern hospital serving a mostly Medicaid
      population in a rural setting, more than 300 parents have used Baby CareLink more
      than 11000 times during the past year. Despite the common wisdom that Medicaid
      families do not have access to the Internet, approximately 85% of the parents
      access Baby CareLink from home, at work, from the library or other public access
      point. The median use of Baby CareLinks from outside the hospital by parents is
      17 separate sessions. In a city hospital in the midwestern US which exclusively
      serves a Medicaid population, experience has been equally encouraging. More than
      70 parents have initiated more than 600 secure sessions with Baby CareLink. In
      contrast to the rural hospital, only 35% of sessions have been initiated outside
      the hospital. DISCUSSION: Experience with Baby CareLink suggests that families
      from all walks of life will use and benefit from collaborative tools that keep
      them informed and involved in the care of their children. The most significant
      barrier to wider deployment is bandwidth limitations into the homes of most
      families. The care of premature infants is a great example of an area where
      medical knowledge and ability has grown dramatically, and where information and
      communication technology holds enormous potential.

PMID- 12810123
TI  - Electronic healthcare record; a way to empower the patient.
AB  - BACKGROUND: Patients are demanding a bigger role in the management of their own
      health and health care. METHODS: The Dutch Federation of Patient and Consumer
      Organizations (NPCF) has initiated several projects in this area. One project
      started in 2001 and aims at contributing to the development of a nation-wide EPR
      system. RESULTS: the NPCF participates in the National Institute for the Care
      Sector (NICTIZ). The NPCF plays an important role in defining the requirements
      regarding authorization and security of the EPR as well as for the legal
      framework in which optimal use can be made of the EPR. NPCF strongly promotes an
      active role of NICTIZ in developing a master plan for the EPR and an active role
      in its implementation. CONCLUSION: Patients and their organizations have to play
      an active role in designing and implementation of an ICT infrastructure for
      health care and in particular of the EPR.

PMID- 12810124
TI  - Organizational issues = change.
AB  - Information systems fail for a number of reasons. Several failure reasons include
      communication, complexity, organization, technology, and leadership. Failure can
      be outlined in four major categories: technical shortcomings, project management
      shortcomings, organizational issues, and the continuing information explosion.
      Change management is the process of assisting individuals and organizations in
      passing from an old way of doing things to a new way of doing things. Change
      management starts early in a technical process, as the need for making major
      changes starts at the conceptual level. This paper briefly covers the people side
      of implementing new information systems, and describes resistance to change and
      various strategies to manage technological change.

PMID- 12810125
TI  - Interaction design theory.
AB  - OBJECTIVE: This paper presents a framework for the design of interactions between
      human and computational agents working in organisations, mediation by
      technological systems. DESIGN: The design of interactions within an organisation
      is viewed from the point of view, not of the technology mediating the new
      interaction, but of the human and computational agents who interact with each
      other. RESULTS: Understanding the limits to individual agent resources permits an
      analysis of the impact that a new interaction will have in a given setting. When
      we look beyond simple interaction settings, we can use the notion of interaction
      equilibria to predict the impact of new information and communication
      technologies within an organisation. Economic supply and demand curves, for
      example, may allow us to make both qualitative and quantitative predictions about
      technological adoption of communication systems. CONCLUSION: Rather than focusing
      solely on characteristics of individual technologies, or psychological and social
      issues, these can be combined to explain the overall decisions that individuals
      make when using technologies. Without necessarily understanding all the local
      decision criteria used by any individual, we can make robust predictions about
      how a group as a whole will interact.

PMID- 12810126
TI  - The mantra of modeling and the forgotten powers of paper: A sociotechnical view
      on the development of process-oriented ICT in health care.
AB  - The recognition that restructuring care processes is central to effective and
      efficient health care will result in the emergence of process-oriented electronic
      patient records (EPRs). How will these technologies come into being? Within
      informatics, it is often stated that to informate something, we should first
      model it. This paper queries whether a detailed modeling of work processes and
      data flows is the primary step that needs to be completed before such EPRs can be
      developed or tailored. Building upon a sociotechnical understanding of ICT
      development, we argue for a reinterpretation of 'models' in such development
      processes. We do so through a reverse engineering of parts of the paper-based
      medical record, which has received little attention in medical informatics. In
      process-oriented EPR design, we argue, modeling should not be conceived as the
      crucial first step in this design, but rather as an intervention in the
      organizational change-processes that constitute proper ICT development.

PMID- 12810128
TI  - When and how to evaluate health information systems?
AB  - AIMS: Evaluating large scale health information systems (HIS) such as hospital
      systems can be difficult. This article discusses the reasons we need to evaluate
      these systems and a range of appropriate methods to carry out evaluations. It is
      written in non-technical language to assist health policy makers and others
      commissioning or implementing such systems, with references and a web site
      containing information for those wishing more detail
      (http://www.ucl.ac.uk/kmc/evaluation/index.html). METHODS: A variety of questions
      relevant to HIS and qualitative and quantitative methods ranging from simple
      before-after to controlled before-after and fully randomised designs, are
      discussed. A running example--evaluating the impact of an order communications
      system on lab requests--is used to illustrate the potential problems, and how
      they can be resolved. RESULTS: The main types of biases affecting impact studies
      and methods to reduce them are described. The article then discusses some trade
      offs between the low cost, easily conducted before-after study with its
      unreliable results versus the more complex, expensive but much more rigorous
      randomised trial. CONCLUSIONS: As would be expected, the correct methods to
      evaluate depend not on what technology is being evaluated--whether an information
      system or a drug--but on the questions the study is designed to answer, and how
      reliable the answers must be. Only those commissioning an evaluation study can
      decide these.

PMID- 12810127
TI  - Implementing computerized physician order entry: the importance of special
      people.
AB  - OBJECTIVE: To articulate important lessons learned during a study to identify
      success factors for implementing computerized physician order entry (CPOE) in
      inpatient and outpatient settings. DESIGN: Qualitative study by a
      multidisciplinary team using data from observation, focus groups, and both formal
      and informal interviews. Data were analyzed using a grounded approach to develop
      a taxonomy of patterns and themes from the transcripts and field notes. RESULTS:
      The theme we call Special People is explored here in detail. A taxonomy of types
      of Special People includes administrative leaders, clinical leaders (champions,
      opinion leaders, and curmudgeons), and bridgers or support staff who interface
      directly with users. CONCLUSION: The recognition and nurturing of Special People
      should be among the highest priorities of those implementing computerized
      physician order entry. Their education and training must be a goal of teaching
      programs in health administration and medical informatics.

PMID- 12810129
TI  - Is medical informatics a mature science? A review of measurement practice in
      outcome studies of clinical systems.
AB  - OBJECTIVE: To determine the extent of explicit attention to formal issues of
      'measurement' in studies examining outcomes of the deployment of clinical
      information systems. METHODS: A structured literature review identified 27
      published studies reporting quantitative outcomes including attitudes, clinician
      behavior, quality of care, and cost of care. These studies were analyzed for
      types of outcome reported, evidence of 'reuse' of measurement methodology, and
      evidence of formal study of the reliability and validity of these measures.
      RESULTS: The 27 studies meeting the inclusion criteria were published between
      1976 and 2002. Several of the studies addressed multiple outcome types. Nine
      examined clinician attitudes; 22 examined health care behaviors; 15 examined
      patient health status/quality of care; and four examined economic indicators.
      There were eight examples of reuse of measurement methods, five of which
      represented reuse within a single research group. Reliability indices were
      reported in three studies. There were no reported validity indices. CONCLUSION:
      Based on this sample of studies, specific attention to issues of measurement is
      sparse in outcome studies of deployed clinical information systems. As such,
      medical informatics does not appear to be on a par with more mature sciences in
      its approaches to measurement of key outcome variables.

PMID- 12810130
TI  - Decision support in medicine: lessons from the HELP system.
AB  - PURPOSE: This report describes an ongoing transition from the HELP Hospital
      Information System to HELP II, a replacement Health Information System built to
      manage clinical information captured in a variety of medical settings. The focus
      of the article is on the medical decision support provided by this system and
      studied by researchers at the University of Utah and Intermountain Health Care
      (IHC), a large health care organization in Utah, for many years. METHODS: Select
      success features of the original HELP system's decision support environment are
      identified and lessons learned are related. Plans for transferring these features
      to HELP II are discussed. RESULTS: The article focuses on four features: (1) the
      importance of easy access to patient data essential for decision support, (2) the
      commitment to continued measurement and revision of both the logic and the
      interventional strategy in a decision support application, (3) experience with
      data mining as a tool for developing decision support tools, and (4) the role of
      clinical reports in supporting the decision making process.

PMID- 12810131
TI  - Health care quality management by means of an incident report system and an
      electronic patient record system.
AB  - BACKGROUND: Quality management in health care services has not been as successful
      as in other industries. OBJECTIVE: To assess the potential contribution of an on
      line incident reporting system (OIRS) and of an electronic patient record (EPR)
      system to quality management in hospitals. METHODS: The two approaches are being
      implemented in Osaka University Hospital. RESULTS: Analysis of the early use of
      the on-line reporting system indicates that this qualitative approach has been
      effective to avoid adverse medical events. The quantitative methodology with the
      EPR is still in the phase of developing. CONCLUSION: Direct data entry by medical
      staff and an EPR based on dynamic templates and a dynamic problem oriented
      approach could be useful for building clinical data repositories that can support
      clinical quality management.

PMID- 12810132
TI  - Report of conference track 1: basic bottlenecks.

PMID- 12810133
TI  - Report of conference track 2: pathways to open architectures.

PMID- 12810134
TI  - Report of conference track 3: patient empowerment.
AB  - Patient empowerment is a philosophy of health care that proceeds from the
      perspective that optimal outcomes of health care interventions are achieved when
      patients become active participants in the health care process. Under a patient
      empowerment philosophy, patients and clinicians jointly set goals, select
      interventions, and assess outcomes according to mutually-defined parameters.
      Employing patient empowerment as an information systems design philosophy leads
      to creation of computerized information resources, management systems and
      telehealth innovations in a manner that insures patients' abilities to
      participate as full partners in health care. Discussions in the track 3
      discussion group led to refinement of the concept from patient empowerment to
      patient engagement. This report reflects the discussions by the participants.

PMID- 12810135
TI  - Report of conference Track 4: socio-technical issues of HIS.

PMID- 12810136
TI  - Report on conference track 5: evaluation metrics and outcome.

PMID- 12810138
TI  - Analysis model for planning chemical dependence treatment systems.
AB  - Statewide needs assessments commonly generate a single estimate of the number of
      persons needing chemical dependence treatment. The present analysis utilizes help
      seeking behavior models and patient placement concepts to break a single
      statewide need estimate into operational units of services and costs that can be
      used for planning and resource allocation. The analyses are presented as
      allocation models for placements, service populations, service capacities, and
      costs. The guide was tested using state data for a target year and the results
      were compared to actual treatment admissions, which revealed a lack of
      convergence. Only 9% of persons were estimated to need intensive residential
      treatment whereas actual admissions to intensive residential treatment accounted
      for 29% of all admissions. The disparities may be accounted for by sampling bias
      of the needs estimate and by the likelihood that persons with more severe
      problems may be overrepresented when only a small proportion of treatment need is
      being met. These findings suggest that if resources become available to narrow
      the treatment gap, a larger proportion of outpatient services and less intensive
      services may be appropriate for the expanded clientele.

PMID- 12810139
TI  - The toughest job you'll ever love: a Pacific Northwest Treatment Workforce
      Survey.
AB  - The training, recruitment, and retention of the most qualified professionals for
      the substance abuse treatment workforce is a crucial underlying strategy in the
      improvement of client care. Conducted in the year 2000, this survey of substance
      abuse treatment agency directors and clinical staff in the Pacific Northwest of
      the United States provides the first empirical estimates of issues surrounding
      these goals and points to the need for more aggressive strategies if a quality
      workforce is to be maintained and improved. Results of the survey indicate that
      there is an average of 25% turnover per year among treatment agency staff, and
      that the vast majority of this turnover is voluntary and stays within the
      treatment profession. Agency management and direct service staff differ in their
      perceptions of the recruitment and retention approaches currently in place in
      their agencies.

PMID- 12810140
TI  - Slowing the revolving door: stabilization programs reduce homeless persons'
      substance use after detoxification.
AB  - This study examined whether homelessness predicted earlier resumption of
      substance use after detoxification, and sought evidence concerning the impact of
      post-detoxification stabilization programs among homeless and nonhomeless
      individuals. Kaplan-Meier plots and proportional hazards models were used to
      determine the association between homelessness, stabilization program use, and
      recurrent substance use in a prospective cohort of persons entering inpatient
      detoxification (n=470). Among 254 persons available at 6 months, 76% reported
      recurrent substance use. Homeless persons not using stabilization programs
      experienced the highest hazard of return to substance use after detoxification,
      Hazard Ratio (HR) 1.26, 95% CI (0.88, 1.80). Homeless persons using these
      programs had the lowest rate of return to substance use: HR 0.61, 95% CI (0.40,
      0.94). A similar impact of stabilization programs was not seen among nonhomeless
      subjects. Post-detoxification stabilization programs were associated with
      improved outcomes for homeless addicted persons. This treatment modality may slow
      the "revolving door" phenomenon of relapse after detoxification among homeless
      persons.

PMID- 12810141
TI  - Ecstasy use among college undergraduates: gender, race and sexual identity.
AB  - We examined a random sample (N=3606) of undergraduates at one large midwestern
      university and explored correlates of ecstasy use and how use varied by gender,
      race, and sexual identity. Approximately 10% of the sample used ecstasy in their
      lifetime; 7% had used within the past year and 3% within the past month. Ecstasy
      was the second most likely illicit drug to be used, marijuana being the first.
      Multivariate logistic regression indicated that while men and women were equally
      likely to have used ecstasy, excessive partying, sexual identity, and grade point
      average were strongly correlated with ecstasy use. After adjusting for several
      factors, the number of sexual partners increased the likelihood of ecstasy use,
      as did self-reported sexual identity; gay, lesbian, and bisexual students were
      more than two times as likely to have used ecstasy in the past year. Significant
      relationships existed between ecstasy use and other substance use such as binge
      drinking, marijuana use, and cigarette smoking. Implications for interventions
      are discussed.

PMID- 12810142
TI  - Methadone versus buprenorphine maintenance for the treatment of heroin-dependent
      outpatients.
AB  - The aim of this study was to assess the efficacy of methadone compared with
      buprenorphine maintenance therapy in heroin-dependent patients over a treatment
      period of 18 weeks. Subjects were randomized to receive either methadone or
      buprenorphine in a comparative double-blind study and consisted of 164 heroin
      dependent male patients who met the DSM-IV criteria for heroin dependence and
      were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41
      patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also
      41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years
      for total buprenorphine group and 33.7 years for methadone group (the mean age
      differences in 4 groups were not statistically significant). Subjects received
      buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg
      per day and were treated in an urban outpatient clinic, offering a 1-hour weekly
      individual counseling session. Days retained in treatment were measured.
      Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose
      group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for
      the 30-mg methadone dose group. Retention in the 8-mg dose group was
      significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose
      group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant.
      Methadone group was significantly better than 1mg buprenorphine dose group
      (p=.004), but was not significantly different from 3 mg buprenorphine dose group
      (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the
      efficacy of buprenorphine for outpatient treatment of heroin dependence and seem
      to indicate that the highest dose (8 mg) of buprenorphine was the best of the
      three doses of buprenorphine, and also support the superiority of 30 mg of
      methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent
      patients to increase their retention in treatment.

PMID- 12810143
TI  - Factors that predict adolescent motivation for substance abuse treatment.
AB  - Many adolescent substance abusers enter treatment because of external pressures
      and thus lack motivation to change their behavior and engage in treatment.
      Because an understanding of adolescent motivation may contribute to improved
      treatment, an investigation of factors that predict motivation was undertaken
      with youth admitted to an adolescent outpatient substance abuse treatment program
      (N=196). At admission, these subjects received a comprehensive biopsychosocial
      assessment. Using multiple regression analysis, factors considered to potentially
      predict motivation were assessed. Of the factors examined, those that involved
      experiencing various negative consequences of substance use emerged as important
      predictors of motivation, whereas severity of substance use did not. Diminished
      awareness of negative consequences of use was consonant with lower motivation,
      suggesting the importance of interventions to help youth recognize negative
      consequences of their substance use. Interventions to enhance motivation are
      likely to become more important as the juvenile justice system increasingly
      refers troubled youth to treatment.

PMID- 12810144
TI  - Adherence to methadone is associated with a lower level of HIV-related risk
      behaviors in drug users.
AB  - There have been limited studies on the potential role of methadone treatment in
      HIV prevention in Asia. Over an 8-week period, we assessed the profiles of drug
      taking and HIV risk behaviors, and tried to identify their relationships with
      methadone adherence in 690 clients who attended Hong Kong's methadone treatment
      program. In the preceding month, 71% of respondents reported using drugs and two
      thirds of those respondents who had injected drugs at some time in their lives
      injected then. Infrequent clients who attended methadone clinics <2 times in the
      previous week were twice more likely to have injected drugs in the last month and
      six times more likely to have >5 injections in the last week than frequent clinic
      attendees. Also, clients taking <60 mg methadone daily were twice more likely to
      have >5 injections in the last week than those taking > or = 60 mg methadone. The
      findings called for further studies on harm reduction programs for HIV prevention
      among drug users in Asian countries.

PMID- 12810145
TI  - Dropout from 12-step self-help groups: prevalence, predictors, and counteracting
      treatment influences.
AB  - Attendance at 12-step self-help groups is frequently recommended as an adjunct to
      professional substance use disorder (SUD) treatment, yet patient dropout from
      these groups is common. This study assessed the prevalence, predictors, and
      treatment-related factors affecting dropout in the first year following treatment
      for 2,778 male patients. Of these, 91% (2,518) were identified as having attended
      12-step groups either in the 90 days prior to, or during, treatment. At 1-year
      followup 40% had dropped out. A number of baseline factors predicted dropout.
      Importantly, patients who initiated 12-step behaviors during treatment were less
      likely to drop out. Further findings suggest patients at highest risk for dropout
      may be at lower risk if treated in a more supportive environment. Clinicians may
      decrease the likelihood of dropout directly, by screening for risk factors and
      focusing facilitation efforts accordingly, and indirectly, by increasing the
      supportiveness of the treatment environment, and facilitating 12-step involvement
      during treatment.

PMID- 12810146
TI  - Twenty-four week maintenance treatment of cigarette smoking with nicotine gum,
      clonidine and naltrexone.
AB  - This research study investigated the effect of nicotine gum, clonidine, and
      naltrexone, in the maintenance treatment of cigarette smoking. In a double blind
      study, 171 nicotine-dependent male subjects who met DSM-IV criteria for nicotine
      dependence and smoking 10 cigarettes or more per day, were allocated randomly to
      three equal groups of 57. Subjects received nicotine gum, clonidine, or
      naltrexone over a 24-week treatment period. The nicotine gum dose was 2 mg every
      1 to 2 h for the first 6 weeks, 2 mg every 2 to 4 h for the next 3 weeks, and 2
      mg every 4 to 8 h for the remaining 15 weeks. The clonidine dose was 0.4 mg and
      the naltrexone dose was 50 mg per day. Continuous abstinence rates were recorded
      weekly for 24 weeks from the quit date. The abstinence rates by treatment groups
      were 36.8% for the nicotine gum group, 19.3% for the clonidine group, and 5.3%
      for the naltrexone group,and all between groups differences were significant.
      These results support the efficacy and safety of nicotine gum and clonidine for
      smoking relapse prevention among Iranian nicotine-dependent patients, but call in
      question the utility of naltrexone treatment for smoking relapse prevention.

PMID- 12810147
TI  - Sources of distress among women in treatment with their alcoholic partners.
AB  - We examined sources of psychological and relationship distress among 90
      nonalcoholic women with alcoholic male partners seeking outpatient, conjoint
      alcohol treatment. Results indicated that greater psychological distress among
      these women was most strongly associated with lower satisfaction with the marital
      relationship, presence of domestic violence, lower frequency of male partner's
      drinking, lower perceived social support from family, and more frequent attempts
      to cope with the partner's drinking. Controlling for psychological distress,
      greater marital satisfaction was associated most strongly with greater attempts
      to reinforce positively the partner's abstinence and with less effort to detach
      from the partner's drinking. Severity of partner's alcohol problems was
      unexpectedly associated with greater marital satisfaction in multiple regression
      analyses, though not in bivariate analyses. Results highlight the close
      connection between psychological and relationship distress and potential
      relations between alcohol-related coping behaviors and both psychological and
      relationship distress.

PMID- 12810148
TI  - Treatment of methamphetamine abuse: research findings and clinical directions.
AB  - Over the past few years, methamphetamine has appeared in mass quantities, in
      part, because of the ease and cost efficiency of manufacturing. With this
      increase in availability, the use of methamphetamine has increased significantly.
      The purpose of this article is to describe the existing treatment options for
      methamphetamine abuse and provide recommendations for practitioners and
      researchers. Methamphetamine abuse adversely impacts physical functioning, brain
      functioning and cognition, social support and social networks, and behavioral
      functioning. Negative consequences have also been documented to the environment
      and communities. In the studies reviewed on effective treatments, interventions
      consisted of aversion therapy, medication, psychosocial treatment, and case
      management. Each specific treatment is described as connected with an overall
      drug treatment program. If methamphetamine abuse continues to increase and the
      consequences continue to be so devastating, researchers and clinicians could
      advance the field by particular focus on the treatment of this type of drug use.

PMID- 12810149
TI  - Domestic violence treatment referrals for men seeking alcohol treatment.
AB  - The annual prevalence of intimate partner violence (IPV) in samples of men
      seeking alcohol treatment has been estimated at 50% or higher. One proposed
      approach to these co-occurring problems is the provision of IPV screening and
      treatment referrals within alcohol treatment programs. The current study found
      that alcohol treatment providers infrequently referred men with a pretreatment
      year history of IPV to domestic violence treatment programs, and that men
      receiving such referrals rarely followed the recommendation and sought additional
      treatment. These findings suggest future research is necessary to identify
      factors that may act as barriers to IPV assessment or referral in alcohol
      treatment settings, factors that may limit client follow-through on such
      referrals, and new strategies for addressing IPV in substance abusing
      populations.

PMID- 12810150
TI  - Serum HER-2/neu in the management of breast cancer patients.
AB  - The clinical role of HER-2/neu, a 185 kD epithelial transmembranous protein, has
      evolved after the approval of the anti-HER-2/neu targeted monoclonal antibody
      trastuzumab (Herceptin) for the therapy of metastatic breast cancer. The
      extracellular domain of HER-2/neu undergoes proteolytic cleavage from the full
      length protein by metalloproteases, and is shed into the blood as a circulating
      antigen. While HER-2/neu gene amplification and/or protein overexpression are
      detected in approximately 25% of primary breast cancers, serum HER-2/neu levels
      are elevated beyond the upper limit of normal in 50 to 60% of stage IV breast
      cancer patients. HER-2/neu in serum can be detected by enzyme immunoassays
      (manual and automated versions). It has been shown to have prognostic and
      predictive information in breast cancer patients. Monitoring for recurrence by
      serum HER-2/neu reaches a high sensitivity for HER-2/neu positive tumors.
      Longitudinal follow-up of patients during any kind of systemic therapy allows for
      monitoring of the therapeutic success. When utilized in these applications, serum
      HER-2/neu testing is complementary to HER-2/neu tissue results and to the
      determination of classical tumor markers such as CA 15-3, CA 27.29 and CEA, which
      are not targeted by specific forms of systemic therapy.

PMID- 12810151
TI  - Studies of apolipoprotein (a) promoter from subjects with different plasma
      lipoprotein (a) concentrations.
AB  - OBJECTIVE: High plasma lipoprotein (a) [Lp(a)] level is closely related to
      coronary heart disease and cerebral thrombosis. The Lp(a) concentration is
      determined primarily by apolipoprotein (a) [apo(a)] gene and APO(a) mRNA
      abundance has been found to vary with apo(a) isoform. Our objective is to
      investigate whether APO(a) promoter activity is related to plasma Lp(a) level.
      DESIGN AND METHODS: The 5' 1.4 kilobases (kb) promoter region of APO(a) was
      cloned into plasmid pGL-2 basic that carries luciferase reporter system. The
      promoter activity was assayed in HepG2 cells. DNA sequence of the promoter was
      also determined. RESULTS: Few nucleotide changes besides the variations at the
      five polymorphic sites: -1270 (TTTTA repeat), -868 (T repeat), -772 (A/G
      variation), +93 (C/T variation) and +121 (A/G variation) were observed in these
      promoters. APO(a) promoter activity differed in subjects with different plasma
      Lp(a) levels. CONCLUSION: The sequence variation of APO(a) promoter region may
      contribute to the variation of its transcription activity.

PMID- 12810152
TI  - Biochemical studies of apoptosis induced by tamoxifen in estrogen receptor
      positive and negative breast cancer cell lines.
AB  - OBJECTIVES: Tamoxifen has been reported to show an efficacy in the treatment of
      breast cancer. Apoptosis could be a major mechanism of its antitumor effect.
      Therefore, this study has been designed to investigate the biochemical mechanisms
      of tamoxifen-induced apoptosis in both ER(+) MCF-7 and ER(-) MDA-MB468 breast
      cancer cell lines. METHODS: Trypan blue dye exclusion test, Annexin V
      Fluorescein/PI flow cytometry, MTT assay and Hoechst 33258 staining were used to
      detect cytotoxicity and apoptosis. The activation of caspase-3 was assayed by
      colorimetric assay kit. Bcl-2 and Bax proteins were estimated by western
      immunoblotting method. RESULTS: Tamoxifen induced apoptosis in both cell lines
      (chi-square test, p < 0.05). Unlike the MCF-7 cells, which responded to the low
      concentration (1 microM), the treated MDA-MB468 cells have mainly been affected
      at a higher dose (20 microM) at which a significant increase was also obtained in
      the caspase-3 activity (chi-square test, p < 0.05). Interestingly, tamoxifen at
      doses higher than 2.5 microM increased cell proliferation in the MCF-7 cells. The
      levels of Bcl-2 and Bax remained unchanged. CONCLUSION: Since tamoxifen has
      induced apoptosis in both cell lines by different mechanisms, it might be
      concluded that there exists ER(+) and ER(-) pathways for the induction of
      apoptosis.

PMID- 12810153
TI  - Expression of human Calbindin-D(9k) correlated with age, vitamin D receptor and
      blood calcium level in the gastrointestinal tissues.
AB  - OBJECTIVE: Calbindin-D(9k) (CaBP-9k) has been thought to be one of the important
      factors of calcium absorption and metabolism in the intestine. The understanding
      of CaBP-9k role in the gastrointestinal tissues is important in human in relation
      with aging and gender, and whether there is any relationship with mineral
      homeostasis and risk for the development of age-related calcium disorders such as
      osteoporosis. DESIGN AND METHODS: The expression of CaBP-9k and vitamin D
      receptor (VDR) was analyzed in the human gastrointestinal tissues with different
      ages and gender. In addition, the correlation among CaBP-9k expression, age and
      calcium concentration in blood was elucidated in these tissues. RESULTS: A
      significant increase in the expression of CaBP-9k mRNA was observed in the bulb
      and 2(nd) portion of duodenum over age in both men and women. However, no
      significant age-associated change in VDR mRNA level was detected in the duodenum.
      The concentration of blood calcium level decreased with age in both men and
      women. CONCLUSION: The duodenal CaBP-9k may be not involved in calcium absorption
      in these tissues. The functional significance of the increase in the intestinal
      CaBP-9k expression with age is not currently clear and requires further
      investigation.

PMID- 12810154
TI  - Polymorphisms in CYP-7A1, not APOE, influence the change in plasma lipids in
      response to population dietary change in an 8 year follow-up; results from the
      Czech MONICA study.
AB  - OBJECTIVES: To evaluate the influence of variation in the genes for
      apolipoprotein E (APOE; epsilon2, epsilon3, epsilon4) and cholesterol-7alpha
      hydroxylase (CYP-7A1; -204A-->C) on plasma lipid level changes. DESIGN AND
      METHODS: 131 males for whom dietary composition markedly changed and total
      cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 - 5.43 +/- 1.06 mmol/L
      in 1996) over an 8 yr follow-up study. Polymorphisms were investigated using PCR.
      RESULTS: APOE genotype influenced plasma total and LDL cholesterol, with carriers
      of the epsilon4 having the highest and epsilon2 carriers the lowest levels, this
      reached borderline significance for cholesterol in 1988 (p = 0.06) and strongly
      affected the 1996 levels of LDL cholesterol (p = 0.008). However, APOE did not
      influence the change in these measures over time. In contrast, the CYP-7A1 -204A-
      >C polymorphism did not affect lipid measures per se but was strongly associated
      with a decrease in plasma total cholesterol [AA -0.38 (+/- 0.20) mmol/L, AC -0.65
      +/- (0.08), CC -1.33 (+/- 0.3) mmol/L, p = 0.01] over the 8 yr time period.
      CONCLUSIONS: Variation in the CYP-7A1 gene may play an important role in an
      individual's sensitivity to dietary composition.

PMID- 12810155
TI  - Diabetic ketoacidosis and its treatment increase plasma 3-deoxyglucosone.
AB  - OBJECTIVES: Highly reactive dicarbonyl compounds are known to be increased by
      hyperglycemia, ketone bodies and lipid peroxidation. This study was carried out
      to investigate the effect of diabetic ketoacidosis (DKA) and its treatment on the
      plasma concentration of 3 deoxyglucosone (3-DG) one of the dicarbonyl compounds.
      DESIGN AND METHODS: 3-DG was measured in 7 children before, during and following
      correction of severe DKA. 3-DG was elevated before treatment (610 nmol/L +or/-
      70) in comparison to baseline (120 h) (200 nmol/L+/or- 17) (p < 0.05). At 6 to 24
      h into treatment 3-DG was further elevated (1080 nmol/L +or/- 80) in comparison
      to both pretreatment (p < 0.05) and baseline (p < 0.05). CONCLUSION: 3-DG is
      significantly elevated before the treatment of DKA and increases further during
      the treatment of DKA. The time course of the increase of 3-DG coincides with the
      time of progression of subclinical brain edema, which occurs in DKA.

PMID- 12810156
TI  - Urine methylmalonic acid measurements for the assessment of cobalamin deficiency
      related to neuropsychiatric disorders.
AB  - BACKGROUND: Detection of cobalamin deficiency is clinically important for a
      better understanding of neuropsychiatric diseases, and why the deficiency occurs
      more frequently than previously anticipated. However, serum cobalamin
      measurements have a limited ability to diagnose a deficiency state. OBJECTIVE: To
      evaluate functional cobalamin status in neuropsychiatric patients using an
      appropriate photometric urine methylmalonic acid (MMA) determination method that
      could be easily adapted to all routine clinical laboratories. METHODS: We
      modified the old photometric method used for determining urinary MMA
      concentrations. MMA measurements were made in first morning urine samples with
      normalizing by creatinine concentrations. The serum cobalamin, total homocysteine
      (tHcy), folate, red cell folate, and urinary MMA concentrations taken from 17
      psychosis, 28 depression, 16 dementia patients and 47 healthy people were
      analyzed using the ROC, correlation and multiple regression analysis. RESULTS:
      The modified method was found to have better recovery (96-103%) and CV% values
      than the old method. Mean +/- SDs of uMMA and cobalamin concentrations were 11.49
      +/- 4.93 mmol/mol creatinine, and 231 +/- 151 pg/mL in psychosis and depression
      group, and 6.04 +/- 1.93 mmol/mol creatinine and 308 +/- 140 pg/mL in control
      group, respectively. Those in the dementia group were 11.53 +/- 4.0 mmol/mol
      creatinine and 231 +/- 84 pg/mL, and in the control group 6.05 +/- 1.94 mmol/mol
      creatinine and 364 +/- 188 pg/mL. There was a good correlation between urinary
      MMA and serum Vitamin B(12) determinations for all groups at a confidence level
      (p) of 99%. The correlation between urinary MMA and red cell folate was also
      significant at p = 95% for depression, psychosis and control groups, and p = 99%
      for dementia group. In the ROC analyses, area under the curve values for uMMA,
      B12 and tHcy were 0.842, 0.796 and 0.728, respectively. CONCLUSIONS: A sensitive
      and easy photometric method has been presented. When cobalamin deficiency is
      suspected in neuropsychiatric patients, photometric urinary MMA determination
      analysis can be the first diagnostic test used. If the urinary MMA concentration
      is above the reference value, serum cobalamin levels can be determined for
      further diagnosis.

PMID- 12810157
TI  - Measurement of glutathione S-transferase and its class-pi in plasma and tissue
      biopsies obtained after laparoscopy and endoscopy from subjects with esophagus
      and gastric cancer.
AB  - OBJECTIVES: To develop an indirect enzyme-linked immunosorbent assay (ELISA) for
      measuring class-pi glutathione S-transferase (GST) in plasma, and tissue biopsies
      obtained from upper gastrointestinal cancer (UGI Ca) patients. METHODS: GST
      activity and GST-pi concentration were detected in normal human squamous
      esophageal epithelium, normal gastric cardia and their corresponding malignant
      tumor biopsies. RESULTS: Plasma GST was significantly higher (p < 0.05) in UGI Ca
      patients as compared to those obtained from normal individuals. Plasma GST-pi
      concentration in normal subjects was 6.6 +/- 1.9 ng/mg protein, whereas it was
      higher in UGI Ca patients (esophageal, 10.0 +/- 1.8; gastric, 10.7 +/- 1.7 ng/mL,
      p <or= 0.01). GST and GST-pi levels were higher in surgically resected tumor
      biopsies as compared to normal tissues adjacent to a tumor (p < 0.05). GST-pi was
      also elevated in malignant esophagus and gastric biopsies taken at endoscopy as
      compared to normal and normal-appearing esophageal tissues (p < 0.05). Total GST
      was also increased significantly in gastric malignant tissues although its
      activity was within the same range in normal and normal-appearing tissues. A
      significant correlation between plasma GST-pi with that in malignant tissues was
      observed. Total GST and GST-pi were also correlated in different malignant
      tissues. CONCLUSIONS: Biopsies obtained at endoscopy can be used satisfactorily
      to measure tumor markers.

PMID- 12810158
TI  - Serum prolidase I activity and some bone metabolic markers in patients with
      breast cancer: in relation to menopausal status.
AB  - OBJECTIVES: The purpose of this study was to investigate the diagnostic value of
      some osteoblastic/osteoclastic biochemical markers and serum prolidase I activity
      in breast cancer (BC). DESIGN AND METHODS: Serum bone gla protein (BGP),
      prolidase I activity, urinary deoxypyridinoline (Dpy) and calcium excretions were
      measured, in metastatic and nonmetastatic BC patients, and in 52 healthy women.
      RESULTS: In patients with metastases, bone turnover markers were found to be
      significantly higher than those in the control group and in patients without
      metastases. Serum prolidase activity in patients with and without metastases was
      also significantly higher than those in the control group, but there was no
      difference between the two patient groups. CONCLUSIONS: Bone turnover has been
      suggested to be accelerated in BC patients with the more pronounced osteolytic
      activation, especially in metastatic state. Serum prolidase in premenopausal
      period appears to be valuable in discriminating cancer patients from controls.
      BGP and to a lesser degree of Dpy, may be useful markers for predicting the
      metastatic bone involvement, as well as for the more cost effective management of
      BC patients and monitoring the effects of antiresorptive therapy of malignant
      osteolysis before any metastasis could be detected by other invasive techniques.

PMID- 12810159
TI  - A correlation between knee cartilage degradation observed by arthroscopy and
      synovial proteinases activities.
AB  - OBJECTIVE: A novel study has been carried out to characterize the amount and
      activity levels of metalloproteinases (i.e., MMP-1, MMP-2, MMP-3, MMP-8, MMP-9
      and MMP-13) and of their inhibitors (i.e., TIMP-1 and TIMP-2) in synovial fluid
      from patients (n = 56) with different degrees of either chondral lesions or knee
      arthritis identified and classified by arthroscopy. DESIGN AND METHODS:
      Zymographies, Western blotting and ELISA tests have been used to correlate the
      disease stage, as determined by arthroscopy, and both the amount and the
      activation state of different MMPs and of their inhibitors. RESULTS: Analysis of
      data obtained demonstrates that the degree of cartilage degradation, as seen by
      arthroscopy, is strictly related to the activity of some synovial MMPs, in
      particular MMP-2 and MMP-13 and on reduced inhibitory effect of MMP-2 by TIMP-2;
      in addition, a serine protease weighing about 125 kDa appears only in patients
      with severe cartilage degradation, i.e., with knee arthritis. CONCLUSIONS: On the
      whole, this is the first study in which an analysis of synovial MMPs/other
      proteinases activity and TIMPs has been strictly related to arthroscopy results
      in patients with different degrees of osteoarthritis. Results indicate that an
      imbalance between specific MMP activities and the amount of TIMPs and of its
      inhibitory efficiency is crucial for the disease evolution and it is related to
      the disease stage.

PMID- 12810160
TI  - Application of denaturing gradient gel electrophoresis (DGGE) to screen for
      mutations of the human glucocorticoid receptor alpha gene (hGRalpha).
AB  - OBJECTIVES: In a previous publication, we had presented a sensitive method to
      detect mutations of the segment of the human glucocorticoid receptor alpha
      (hGRalpha) gene encoding the ligand binding domain (LBD) and part of the DNA
      binding domain (DBD) of hGRalpha, as several types of glucocorticoid resistance
      syndromes have been correlated with mutations in the respective nucleotide
      sequences. However, mutations affecting various regions covering the whole length
      of hGRalpha are increasingly reported in a variety of disease states. We now
      present an expanded screening methodology to detect mutations covering the whole
      length of hGRalpha. DESIGN AND METHODS: We developed a sensitive, simple
      screening PCR-DGGE method to detect mutations in the aminoterminal domain and DNA
      binding domain of the hGRalpha. Wild type hGRalpha cDNA and mutant samples were
      included in the analysis to ensure the accuracy and sensitivity of the method.
      RESULTS: The PCR-DGGE method identified the mutant samples and discriminated them
      from wild type hGRalpha. CONCLUSIONS: The method described is accurate,
      sensitive, simple, cheap and fulfills the critera for a screening method which
      will be useful in delineating possible involvement of hGRalpha mutations in the
      aetiopathology of diseases correlated to derangements of glucocorticoid action.

PMID- 12810161
TI  - Evaluation of a new pretreatment reagent for use with the EMIT 2000 cyclosporine
      assay.
AB  - OBJECTIVES: Evaluate the performance of the new pretreatment (NPT) reagent for
      use with the EMIT cyclosporine A (CsA) assay. DESIGN AND METHODS: Samples from
      transplant patients receiving CsA were tested using a COBAS MIRA S. RESULTS: A
      downward shift in target values for commercial controls was observed using the
      NPT reagent. There was excellent correlation for patient results when comparing
      the NPT reagent with methanol pretreatment. CONCLUSION: The NPT reagent is an
      acceptable substitute for methanol in the EMIT(R) extraction procedure for CsA.

PMID- 12810162
TI  - Analytical evaluation of hemoglobin A(1c) dual kit assay on Bio-Rad Variant II:
      an automated HPLC hemoglobin analyzer for the management of diabetic patients.
AB  - OBJECTIVES: To evaluate the analytical performance of the Bio-Rad Variant II
      HbA(1c) dual kit assay. DESIGN AND METHODS: Precision, carryover, linearity and
      analytical range were investigated. 139 patients' HbA(1c) results analyzed by the
      Variant II were compared to the Variant I method. 49 blood samples analyzed by
      the Variant II at Toronto Medical Laboratories (TML) were compared to the Variant
      II at Hospital for Sick Children (HSC). RESULTS: Total imprecision was less than
      2% for the Variant II assay. The method had a wide analytical range with no
      carryover. HbA(1c) results were not changed after switching back and forth from
      the beta thalassemia to HbA(1c) assay. The Variant II showed an average of 0.0027
      negative bias compared to the Variant I method. There was an average of 0.0020
      negative bias for HbA(1c) results on the Variant II at TML compared to the
      Variant II at HSC. CONCLUSIONS: HbA(1c) analysis on the Variant II HbA(1c) dual
      kit is a relatively fast and reproducible method.

PMID- 12810165
TI  - The surface antigen CD45R identifies a population of estrogen-regulated murine
      marrow cells that contain osteoclast precursors.
AB  - We examined the osteoclastogenic potential of murine bone marrow cells that were
      fractionated according to their expression of the surface antigen CD45R.
      Osteoclast-like cells (OCL) with many authentic osteoclast characteristics
      readily formed in purified CD45R(+) murine bone marrow cell cultures after
      treatment with receptor activator of nuclear factor kappaB ligand (RANKL) and M
      CSF. Ovariectomy (Ovx) caused a 1.5- to 2-fold increase in OCL number in
      unfractionated and CD45R(+) murine bone marrow cell cultures without affecting
      OCL formation in CD45R(-) marrow cells. Limiting dilution assays confirmed that
      Ovx caused an increase in osteoclast precursor cell number in CD45R(+) but not
      CD45R(-) cells. Mice deficient in the type 1 IL-1 receptor (IL-1R1 KO) do not
      lose bone mass after Ovx. We found that unfractionated, CD45R(+), and CD45R(-)
      bone marrow cells from IL-1R1 KO mice showed no increase in OCL formation in
      vitro after Ovx. In both the wild-type (WT) and the IL-1R1 KO mice Ovx was
      associated with a 2-fold increase in pre-B-lymphocytes. About 1.3-3.5% of murine
      marrow cells expressed surface RANK (the receptor for RANKL) while about 11.9-15%
      of murine bone marrow cells expressed c-Fms (the receptor for M-CSF). There was
      little effect of Ovx on cells expressing either RANK or c-Fms. These results
      demonstrate that CD45R expression identifies a subset of murine bone marrow cells
      whose ability to form OCL in vivo is regulated by estrogen in WT but not IL-1R1
      KO cells. The effects of estrogen on bone mass may be related to these responses.

PMID- 12810166
TI  - In vivo bone formation in fracture repair induced by direct retroviral-based gene
      therapy with bone morphogenetic protein-4.
AB  - This study sought to develop an in vivo gene therapy to accelerate the repair of
      bone fractures. In vivo administration of an engineered viral vector to promote
      fracture healing represents a potential high-efficacy, low-risk procedure. We
      selected a murine leukemia virus (MLV)-based retroviral vector, because this
      vector would be expected to target transgene expression to the proliferating
      periosteal cells arising shortly after bone fracture. This vector transduced a
      hybrid gene that consisted of a bone morphogenetic protein (BMP)-4 transgene with
      the BMP-2 secretory signal to enhance the secretion of mature BMP-4. The MLV
      vector expressing this BMP-2/4 hybrid gene or beta-galactosidase control gene was
      administered at the lateral side of the fracture periosteum at 1 day after
      fracture in the rat femoral fracture model. X-ray examination by radiograph and
      peripheral quantitative computed tomography at 7, 14, and 28 days after fracture
      revealed a highly significant enhancement of fracture tissue size in the MLV-BMP
      2/4-treated fractures compared to the control fractures. The tissue was
      extensively ossified at 14 and 28 days, and the newly formed bone exhibited
      normal bone histology. This tissue also exhibited strong immunohistochemical
      staining of BMP-4. Additional control and MLV-BMP-2/4-treated animals each were
      monitored for 70 days to determine the fate of the markedly enhanced fracture
      callus. Radiographs showed that the hard callus had been remodeled and
      substantial healing at the fracture site had occurred, suggesting that the union
      of the bone at the fracture site was at least as high in the BMP-4-treated bone
      as in the control bone. There was no evidence of viral vector infection of
      extraskeletal tissues, suggesting that this in vivo gene therapy for fracture
      repair is safe. In summary, we have demonstrated for the first time that a MLV
      based retroviral vector is a safe and effective means of introducing a transgene
      to a fracture site and that this procedure caused an enormous augmentation of
      fracture bone formation.

PMID- 12810167
TI  - Modification of gene expression induced in human osteogenic and osteosarcoma
      cells by culture on a biphasic calcium phosphate bone substitute.
AB  - Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells
      are very promising alternatives to autologous bone graft. Along this line, the
      development of in vitro models, dedicated to analyze the influence of these
      biomaterials on osteogenic cells, will help to improve the performance of these
      bone substitutes. In the present work we analyzed the effects of a macroporous
      biphasic calcium phosphate ceramic (BCP, Triosite) on three different human
      osteosarcoma cell lines and on human primary osteogenic cells and compared this
      culture substratum to traditional culture on plastic. We showed that all these
      osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a
      different spatial organization for osteosarcoma cells compared to normal
      osteogenic cells. We also demonstrated that osteoblastic marker genes such as
      Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed
      at similar levels by these cells cultured on either substratum, suggesting that
      adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we
      provided the first evidence of differences of cytokine expression profiles
      revealed on this Ca-P ceramic as compared to expression in classical culture.
      These modifications affected the expression of cytokines such as TGF-beta1, G
      CSF, and IL-3 and were quantitatively different between osteosarcoma cells and
      normal osteogenic cells. Given the role of these cytokines in bone biology and in
      hematopoiesis, these results obtained in vitro suggest that the BCP ceramic
      studied here could stimulate osteogenesis in vivo by activating cellular
      processes during bone formation and healing. This study highlights the notion
      that the nature of the culture substratum must be taken into account when
      studying bone cell biology in vitro. Owing to the nature and spatial organization
      of the BCP, our hypothesis is that culture on BCP is closer to the physiological
      situation than culture on plastic.

PMID- 12810168
TI  - Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA
      expression and iPTHrP secretion.
AB  - We used both clonal osteoblast-like cells and primary calvarial osteoblastic
      cells to examine the role of Hedgehog in osteoblast biology. Primary osteoblasts
      and several clonal osteoblast-like cell lines express Indian hedgehog (Ihh), and
      genes encoding both components of its receptor, patched (Ptc) and smoothened
      (Smo). Moreover, Ihh is relatively increased in phenotypically mature clonal
      cells and it increases by fivefold in primary osteoblasts as they mature in
      culture. Recombinant N-terminal Sonic Hedgehog (rSHH-N) upregulates Ptc and Gli-1
      in osteoblasts, classical transcriptional targets. Furthermore; in response to
      rSHH-N, immunoreactive parathyroid hormone-related peptide (iPTHrP) secretion is
      transiently increased in medium conditioned by primary osteoblasts. Changes in
      PTHrP expression mirror those of iPTHrP, except in late cultures, when mRNA
      levels remain relatively elevated in response to rSHH-N. Gli-1, but not Ptc,
      becomes resistant to treatment with rSHH-N over a time course paralleling that of
      PTHrP, suggesting that mechanisms regulated by Gli-1 affect PTHrP. Last, rSHH-N
      increases formation of mineralized bone nodules and it accelerates expression of
      alkaline phosphatase, alkaline phosphatase activity, and mineralization. Taken
      together, these data suggest a functional role for Hedgehog protein in osteoblast
      recruitment and differentiation, which includes stimulation of PTHrP expression
      and secretion.

PMID- 12810169
TI  - Expression of RANK is dependent upon differentiation into the
      macrophage/osteoclast lineage: induction by 1alpha,25-dihydroxyvitamin D3 and TPA
      in a human myelomonocytic cell line, HL60.
AB  - Receptor activator of nuclear factor (RANK) is a member of the tumor necrosis
      factor receptor superfamily indispensable for osteoclast differentiation.
      However, little is known about the regulatory mechanism of RANK expression. In
      the present study, RANK expression during macrophage/osteoclast differentiation
      was investigated using a human myelomonocytic cell line, HL60, capable of
      differentiating into mature osteoclasts under appropriate conditions. RANK mRNA
      expression was barely detectable in growing HL60 cells. We found that treatment
      with 1alpha,25-dihydroxyvitamin D(3) and TPA resulted in an apparent induction of
      RANK mRNA and protein in association with differentiation into the
      macrophage/osteoclast lineage. Induction of RANK was time and dose dependent and
      lineage specific. Moreover, RANK induction was blocked by an RNA polymerase II
      inhibitor, suggesting an involvement of a transcriptional mechanism. The induced
      RANK was functional as it was able to bind RANK ligand and activate NF-kappaB. In
      the induced HL60 cells expressing both c-Fms and RANK, RANK mRNA expression was
      further enhanced by RANKL, but not by macrophage colony-stimulating factor. These
      results suggest a positive feedback regulation of RANK expression by its own
      intracellular signaling. The in vitro system described here may be a useful model
      to elucidate the regulatory mechanism of RANK expression and its role in human
      osteoclastogenesis.

PMID- 12810170
TI  - Changes in vasoactive factors associated with altered vessel morphology in the
      tibial metaphysis during ovariectomy-induced bone loss in rats.
AB  - We hypothesized that estrogen deficiency induces changes in bone vascularization
      which might be involved in bone loss mechanisms. First, we studied gene
      expression of angiogenic (vascular endothelial growth factor (VEGF), fibroblast
      growth factor-2 (FGF-2)) and vasodilator (endothelial nitric oxide synthase
      (ecNOS), neuronal NOS (nNOS), inducible NOS (iNOS), PTH-related protein (PTHrP),
      and its receptor PTH/PTHrP) factors in proximal tibial metaphysis of
      ovariectomized (OVX) rats and OVX 17beta-estradiol-treated rats at 3, 7, and 14
      days. We then evaluated bone and vessel histomorphometry in secondary spongiosae
      by infusing vessels with a mixture of India ink/barium sulfate after 7 and 14
      days of OVX. After 7 days expression of angiogenic and vasodilator factors
      decreased, concomitant with a decrease in the bone vessel number and possibly
      area. After 14 days all factors except FGF-2 exhibited either increased or
      normalized expression, which was associated with the stimulation of both bone
      formation and resorption. 17beta-Estradiol administration for 7 or 14 days
      prevented not only the OVX-induced changes in bone remodeling but also the
      morphological alterations observed in bone vessels. It also prevented the
      alterations in the expression of genes modified by OVX, except for that of FGF-2
      whose transcription was similarly down-regulated in OVX rats with or without
      estrogen treatment.

PMID- 12810171
TI  - Estrogen deposits extra mineral into bones of female rats in puberty, but
      simultaneously seems to suppress the responsiveness of female skeleton to
      mechanical loading.
AB  - To first test the possible effect of gender on the responsiveness of growing rat
      skeleton to mechanical loading, 5-week-old littermates of 25 male and 25 female
      rats were subjected to either free-cage activity or treadmill training for a
      period of 14 weeks (experiment 1). Using peripheral quantitative computed
      tomography (pQCT) and mechanical testing of the femoral neck, we observed female
      rats exhibiting a clearly lower responsiveness to external loading than male rats
      (+3.0% vs +25% in cross-sectional area (CSA), +4.2% vs +27% in the bone mineral
      content (BMC), -0.6% vs +10% in volumetric bone mineral density (BMD), and +4.7%
      vs +28% in fracture strength (F(max)) of the femoral neck). Also, relative to the
      mechanical demands placed on the skeleton, the bones of the young female rats
      were considerably denser (>50%) than those of the males. In the subsequent
      experiment 2, we repeated the above-noted first experiment with 33-week-old rats
      and observed virtually identical exercise-induced benefits (+2.1% vs +10% in CSA,
      +3.4% vs +18% in BMC, +2.5% vs +23% in BMD, and -1.1% vs +27% in F(max) in
      females vs males, respectively) and the growth/puberty-related condensation of
      mineral into female bones. Finally, in experiment 3, 60 littermates of 3-week-old
      female rats were first subjected to sham operation or ovariectomy and then
      further randomized to exercise or control groups, respectively, to study whether
      the condensation of mineral into female bones and their lower responsiveness to
      loading were attributable to the effects of estrogen. At the end of the 16-week
      intervention, our pQCT and mechanical testing analysis showed not only the
      anticipated effect of reduced bone density in the ovariectomized rats (
      approximately -20%) but also the hypothesized better responsiveness to mechanical
      loading in these estrogen-depleted rats (-3.5% vs +9.1% in CSA, -0.4% vs +12% in
      BMC, +4.4% vs +9.6% in BMD, and -4.2% vs +16% in F(max) in SHAM vs OVX,
      respectively). In conclusion, the results of our series of three experiments
      suggest that as such estrogen seems to have very little primary effect on the
      sensitivity of female bone to respond to external loading, but rather deposits
      extra stock of mineral into female bones in puberty. This estrogen-driven extra
      condensation of the female skeleton seems to persist into adulthood,
      simultaneously damping the responsiveness of the female skeleton to mechanical
      loading.

PMID- 12810172
TI  - Evidence for an extensive collagen type III/VI proximal domain in the rat femur.
      I. Diminution with ovariectomy.
AB  - Collagenous proteins other than Type I have received little attention in
      hypogonadal bone loss. Using femora from 25 young (2.5 months) and older (11
      months) control and ovariectomized adult rats killed 1-4 months postoperation,
      cancellous atrophy was histologically confirmed, and the immunolocalization of
      collagen Type III was examined. This occurred as numerous immunofluorescent
      Sharpey-like fibers, 5-25 microm thick, regularly associated with collagen Type
      VI, which ramified the femoral cortex. Sequential transverse cryosections enabled
      the mapping of the fibers in three-dimensions, demonstrating that they
      constituted an extensive subperiosteal domain which may be a lasting legacy of
      early skeletal development. Fiber density was greatest in the trochanters and
      femoral neck. The domain tapered distally and was apparently anchored into the
      mid-shaft by intracortical cartilaginous islands, staining for collagen Type VI
      (as well as Type II and fibronectin). Ovariectomy caused disconnection of the
      fibers and reduced the proximal domain of both young and older animals,
      previously positive areas of the cortex becoming negative. It is concluded that
      collagen Type III/VI occupies a substantial, discrete domain in the rat proximal
      femur as a complex extension of the periosteum. Diminution of this cortical
      domain with trabecular atrophy suggests that it has a proactive or reactive role
      in determining bone mass and strength by facilitating musculoskeletal exchange in
      a form that is disengaged by ovariectomy.

PMID- 12810173
TI  - Evidence for an extensive collagen type III proximal domain in the rat femur. II.
      Expansion with exercise.
AB  - Exercise in youth may affect bone "quality" as well as quantity. Using the rat
      model, 1.5-month-old females were divided into four weight-matched groups,
      exercised short-term (6 weeks, E(s), n = 20) and long-term (14 weeks, E(L), n =
      10) by access to monitored running wheels, and corresponding "sedentary" controls
      (S(S) short-term, n = 20; S(L) long-term, n = 10). Femora were either plastic
      embedded or fresh-frozen. Transverse histological slices, 100 microm thick, were
      cut midshaft, while similar cryosections, 8 microm thick, were prepared from the
      same site and also coronal to the femoral neck region. An image analyser measured
      femoral neck and midshaft microarchitecture, while immunostaining localized
      collagen type III-rich fibres (CIII, an index of Sharpey fibre insertions) and
      osteopontin-rich osteons (OPN, an index of remodelling). Exercise increased
      cortical bone (proximal width +18%, midshaft area +7%). It also raised cancellous
      bone volume (+25%) by trabecular thickening (+30%) with more intraosseous
      vascularity and new trabecular interconnections (node-terminus ratio, +57%;
      trabecular pattern factor, -147%; marrow star volume. -48%). In the cortex a
      prominent discrete subperiosteal domain became wider (+50% midshaft) with
      exercise and contained more numerous (+15%) CIII-stained fibres. In contrast the
      encircled inner bone developed more numerous (+14%) OPN-rich osteons. It is
      concluded that short-term voluntary exercise augments both cortical and
      cancellous microarchitecture. It also alters protein composition, such that
      expanding arrays of Sharpey's fibres within a circumferential proximal domain
      (Part I) interconnect more powerfully with the musculature and interface more
      robustly with the core bone that in response becomes more vascular and
      biodynamic, providing further insight into how muscle mass may be skeletally
      translated.

PMID- 12810174
TI  - Skeletal unloading induces resistance to insulin-like growth factor I on bone
      formation.
AB  - Skeletal unloading results in an inhibition of bone formation associated with a
      decrease in osteoblast number, impaired mineralization of bone, and altered
      proliferation and differentiation of osteoprogenitor cells. Although such changes
      are likely to be mediated by multiple factors, resistance to the growth-promoting
      action of insulin-like growth factor I (IGF-I) has been hypothesized to play an
      important role. To determine whether skeletal unloading induces resistance to IGF
      I on bone formation, we examined the response of unloaded (hindlimb elevation)
      and normally loaded tibia and femur to IGF-I administration. To eliminate the
      variable of endogenous growth hormone production and secretion during exogenous
      IGF-I administration, we used growth hormone-deficient dwarf rats (dw-4). The
      rats were given IGF-I (2.5 mg/kg/day) or vehicle during 7 and 14 days of
      unloading or normal loading. This significantly increased the serum level of IGF
      I in both the normally loaded and unloaded rats. Unloading did not affect the
      serum level of IGF-I in the vehicle-treated rats. IGF-I markedly increased
      periosteal bone formation at the tibiofibular junction of normally loaded rats.
      Unloading decreased bone formation in the vehicle-treated rats, and blocked the
      ability of IGF-I to increase bone formation. On the other hand, IGF-I increased
      periosteal bone formation at the midpoint of the humerus (normally loaded in this
      model) in both hindlimb-elevated and normally loaded rats. IGF-I significantly
      increased osteogenic colony number, total ALP activity, and total mineralization
      in bone marrow osteoprogenitor (BMOp) cells of normally loaded rats. Unloading
      reduced these parameters in the vehicle-treated rats, and blocked the stimulation
      by IGF-I. Furthermore, IGF-I administration (10 ng/ml) in vitro significantly
      increased cell proliferation of the BMOp cells isolated from normally loaded
      bone, but not that of cells from unloaded bone. These results indicate that
      skeletal unloading induces resistance to IGF-I on bone formation.

PMID- 12810175
TI  - Serum levels of osteoprotegerin increase with age in a healthy adult population.
AB  - Regulation of the balance of osteoblastic and osteoclastic activity is critical
      for the understanding of normal cell biology and forms the basis of metabolic
      bone diseases. Our study reports about influences of age and gender on serum
      levels of osteoprotegerin (OPG) and its association to other clinical parameters
      of bone metabolism in a precisely determined cohort of 1134 healthy subjects at
      17 Austrian outpatient bone clinics, aged between 19 and 96 years (females n =
      687, 50 +/- 21 years, 19-94, and males n = 447, 52 +/- 13.5 years, 24-96). Mean
      OPG serum levels for all participants were 50.83 +/- 51.47 pg/ml (n = 1134;
      median 36, 2-584) and we observed a sharp increase in females after 60 years and
      in males after 70 years of age. OPG serum levels increased significantly by age,
      2.1 pg/ml in females and 1.9 pg/ml in males for every year (P < 0.0001).
      Correlation of OPG serum levels and several bone parameters of bone metabolism
      showed that OPG negatively correlated with serum iPTH (r = -0.14; P < 0.001) and
      with serum estradiol in females (r = -0.16, P < 0.0001). Bone mineral density
      measured by DXA method at the spine and at the hip did not correlate with OPG
      serum levels, except a borderline negative correlation at the trochanteric region
      (r = -0.1, P < 0.05) in females only. Our results show a significant increase of
      osteoprotegerin with age in healthy females and males but fluctuations do not
      predict bone mineral density under in vivo conditions.

PMID- 12810176
TI  - Oral ibandronate: changes in markers of bone turnover during adequately dosed
      continuous and weekly therapy and during different suboptimally dosed treatment
      regimens.
AB  - The aims of the present study were to investigate how changes in the cumulative
      dose and the frequency of dosing influence the short-term antiresorptive efficacy
      of oral ibandronate treatment and whether serial measurements of bone markers
      could provide a useful diagnostic tool for the revelation of noncompliance to
      established treatments with antiresorptive drugs. Study participants were 200
      healthy women 50-70 years old (mean 63.1 years) with a lumbar spine BMD t-score
      of -1 to -5. Women were randomly allocated to receive treatment with oral
      ibandronate according to one of the following eight dosing regimes: (1) 2.5 mg
      daily for 84 days; (2) 20 mg weekly for 84 days; (3) 2.5 mg daily for 28 days +
      no treatment for 56 days; (4) 2.5 mg daily for 28 days + 2.5 mg weekly for 56
      days; (5) 2.5 mg daily for 28 days + 2.5 mg three times weekly for 56 days; (6)
      2.5 mg daily for 14 days + 2.5 mg three times weekly for 56 days; (7) 2.5 mg
      three times weekly for 84 days; (8) no treatment for 168 days. Study parameters
      were the serum concentration of the C-terminal telopeptide of collagen type I (s
      CTX, resorption marker) and N-MID osteocalcin (formation marker) measured by
      enzyme-linked immunosorbent assay. Oral treatment with ibandronate 20 mg weekly
      (cumulative dose 240 mg) resulted in greater final inhibition in s-CTX and area
      under the curve (AUC) compared to the 2.5 mg daily treatment (cumulative dose 210
      mg), indicating that as long as optimal doses are administered the frequency of
      dosing has secondary importance for overall efficacy. When the cumulative dose
      was 130 mg or less, the final degree of inhibition was still the function of the
      cumulative dose, but the overall efficacy estimated by the AUC was also under the
      influence of the frequency of dosing. These observations suggest that serial
      measurements of s-CTX may provide a useful diagnostic tool for the early
      revelation of suboptimal dosing or noncompliance to already optimized therapies
      with antiresorptive agents.

PMID- 12810177
TI  - Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk.
AB  - The etiologic role of dietary calcium and vitamin D intake in primary prevention
      of osteoporotic fractures is uncertain, despite considerable research efforts.
      With the aim to examine these associations with an improved precision, we used
      data from a large population-based prospective cohort study in central Sweden. We
      estimated nutrient intake from a self-administered food-frequency questionnaire
      filled in by 60,689 women, aged 40-74 years at baseline during 1987-1990. During
      follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip
      fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox
      proportional hazards models. We found no dose-response association between
      dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was
      1.01 (95% CI 0.96-1.06) per 300 mg calcium/day and the corresponding risk of any
      osteoporotic fracture was 0.99 (95% CI 0.96-1.03). Furthermore, women with an
      estimated calcium intake below 400 mg/day and those with a calcium intake higher
      than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with
      intermediate calcium intakes: RR 1.07 (95% CI 0.92-1.24) and RR 1.00 (95% CI 0.79
      1.27), respectively. Vitamin D intake was not associated with fracture risk.
      Furthermore, women in the highest quintiles compared to the lowest quintiles of
      both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all
      fractures (95% CI 0.88-1.17). Dietary calcium or vitamin D intakes estimated at
      middle and older age do not seem to be of major importance for the primary
      prevention of osteoporotic fractures in women.

PMID- 12810178
TI  - Associations of hormone replacement therapy with bone structure and physical
      performance among postmenopausal women.
AB  - The purpose of this cohort study was to focus on factors associated with bone
      mass and structure of lower limbs and physical performance after menopause.
      Eighty nonsmoking women with a mean age of 62.1 (SD 0.8) years participated in
      the study. They were classified into two groups by their use of hormone
      replacement therapy (HRT), either the current users (n = 43) or the never or
      discontinued users (n = 37). The tibial shaft and distal tibia were scanned with
      peripheral computed tomography. For the shaft region, the bone mineral content
      (BMC, g), cortical density (CoD, g/cm(3)), cortical area (CoA, mm(2)), and
      section modulus (BSI, mm(3)) were determined. For the distal part, the evaluated
      variables were BMC, total area (ToA), ratio of cortical to total area (CoA/ToA),
      trabecular density (TrD, g/mm(3)), cortical thickness, BSI, and buckling ratio.
      Isometric and dynamic muscle strength of the leg extensors, agility and postural
      sway, and cardiorespiratory capacity (VO(2max)) were measured. Unadjusted values
      for all bone variables were slightly higher among the HRT users compared to
      nonusers, with the exception of TrD with no difference. After controlling for
      body weight, the mean differences (95% confidence interval) remained significant
      for CoD of the tibial shaft and BSI of the distal tibia, the mean between-group
      differences being 1.5% (0.4 to 2.5%) and 23.0% (7.1 to 41.3%), respectively.
      Underlying the greater bending strength, HRT users had thicker cortices and a
      greater ratio of CoA/ToA. No differences existed between the two study groups for
      lower limb isometric or dynamic power, cardiorespiratory capacity, or postural
      balance or sway. HRT may offer protection against bone loss and maintain bone
      strength, although its ability to improve physical performance is not evident.

PMID- 12810179
TI  - Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and
      osteoporotic fracture.
AB  - Genetic factors play an important role in the pathogenesis of osteoporosis and
      several candidate gene polymorphisms have been implicated in the regulation of
      this process. One of the most widely studied is the Sp1 binding site polymorphism
      in the COL1A1 gene. This polymorphism has been associated with BMD and
      osteoporotic fracture in several studies, but the data from different studies
      have been conflicting. Here we have attempted to clarify the association between
      COL1A1 Sp1 alleles, BMD, and osteoporotic fracture by conducting a meta-analysis
      of 26 published studies including 7849 participants. Under a fixed effects model,
      BMD values at the lumbar spine (6800 subjects) were significantly lower in the
      "Ss" genotype group when compared with "SS" homozygotes (standardized mean
      difference = 0.131 [95% CI, 0.06,0.16], P = 0.00005) but the difference was not
      significant for the "ss" comparison (0.09 [-0.03,0.21], P = 0.13). At the femoral
      neck (6750 subjects) BMD values were lower in the "Ss" genotype (0.14
      [0.08,0.19], P < 0.00001) and lower still in the "ss" genotype group (0.19
      [0.07,0.31], P = 0.001). Similar results were found when the data were analyzed
      under a random effects model. Analysis of fracture data (6961 subjects) showed an
      increased odds ratio for any fracture in "Ss" subjects (1.26 [95% CI 1.09,1.46],
      P = 0.002) and an even greater increase in "ss" subjects (1.78 [1.30,2.43], P =
      0.0003). Subgroup analysis showed that increased risk was largely attributable to
      vertebral fracture where the odds ratio was 1.37 [1.15,1.64] for "Ss" (P =
      0.0004) and 2.48 [1.69,3.65] for "ss" (P < 0.00001). The risk of nonvertebral
      fracture was not increased in relation to the COL1A1 genotype, although power to
      detect an effect was limited by the fact that fewer studies had analyzed
      nonvertebral fracture. We conclude that the COL1A1 Sp1 alleles are associated
      with a modest reduction in BMD and a significant increase in risk of osteoporotic
      fracture, particularly vertebral fracture.

PMID- 12810180
TI  - Health-related quality of life and cost of ambulatory care in osteoporosis: how
      may such outcome measures be valuable information to health decision makers and
      payers?
AB  - The objective was to quantify the outcome of osteoporosis (OP) in terms of health
      related quality of life (HR-QOL) and cost of ambulatory care and to look at the
      association between these two outcomes variables. A cross-sectional health survey
      of 4800 Belgian individuals over the age of 45 years was used. Individuals having
      reported OP were retrieved and for each of them, at least two matched individuals
      for age, sex, residency location, and health insurance status were identified.
      All individuals were assessed with the SF-36. The two major health insurance
      providers furnished cost value for ambulatory care. HR-QOL and cost data were
      compared between the OP group and control group. Beta-coefficients from linear
      regression were calculated to give information on the relative importance of the
      association between each SF-36 dimensions and cost of ambulatory care. Of 4796
      individuals appropriately surveyed, 221 (4.8%) reported OP. The control group
      included 651 individuals. The OP group experienced impaired HR-QOL compared to
      their matched counterparts, all the difference in mean or median SF-36 scores
      being significant at the level of P < 0.001. Osteoporotic respondents averaged
      816 in cost of ambulatory care whereas controls averaged 579 (P < 0.001). When
      looking at detailed comparisons between categories of cost, costs in the OP group
      far exceeded those in the control group, all the differences being significant at
      the level of P < 0.001 except for home health nurse (P = 0.012). In the OP group,
      vitality dimensions played the most important role in the determination of cost
      (beta = -0.28, P < 0.001), followed by physical functioning (beta = -0.26, P <
      0.01), general health, and social functioning (beta = -0.23, P < 0.01). This
      study evidences the burden of OP in terms of HR-QOL and cost of ambulatory care.
      Exploring the association between HR-QOL and cost show that mental dimension such
      as vitality can play an important role in the determination of cost.
      Conclusively, they should not be neglected in future management of OP.

PMID- 12810181
TI  - Controversies in respiratory diseases and their management.

PMID- 12810182
TI  - Genes for asthma: much ado about nothing?
AB  - The identification of genes that make individuals susceptible to developing
      asthma is an area of increasing focus by both academic and industrial groups. The
      complexity of asthma genetics has made the identification of susceptibility genes
      difficult; however, genome-wide screens followed by positional cloning have
      started to identify such genes for both asthma and asthma-related traits. In
      addition, evidence from candidate gene studies indicates that gene-gene
      interactions also play an important role in conferring genetic risk for asthma
      development. Although progress in terms of identifying new therapeutic targets
      has not been dramatic, our understanding of the complexity of the genetic basis
      of asthma has greatly increased. There can be little doubt that, in the future,
      this knowledge will lead to fundamental insights into the molecular
      pathophysiology of asthma and the development of new therapies.

PMID- 12810183
TI  - Immunomodulation in asthma: mechanisms and possible pitfalls.
AB  - Atopic diseases, including atopic asthma, are characterized by T helper cell
      (Th)2 cytokine pathology. The increased prevalence of asthma and allergic
      diseases, as well as Th1-associated conditions, is linked to 'excessive' hygiene.
      Several new immunomodulatory strategies in asthma and allergy, such as peptide
      therapy and DNA vaccines, show promise and are under clinical evaluation. They
      appear to exert their effects by producing a Th2 to Th1 shift, as well as
      inducing regulatory cytokines such as interleukin-10 and transforming growth
      factor-beta. There is no evidence that such approaches are associated with Th1
      pathology in humans, although lung inflammation induced by Th1 cells has been
      observed in mice. IL-10 plays a key regulatory role in dampening both Th2- and
      Th1-associated diseases. Failure to stimulate regulatory responses could explain
      the rising trends in allergy and autoimmunity, and also partly explain the mode
      of action of allergen-injection immunotherapy and new immunomodulatory
      approaches.

PMID- 12810184
TI  - The eosinophil as a therapeutic target in asthma: beginning of the end, or end of
      the beginning?
AB  - A major goal in asthma therapy is to reduce or prevent the inflammatory response
      associated with bronchial hyperresponsiveness, reversible airway obstruction and
      airway remodelling. However, because of the complex nature of the disease, a
      single target for such an ideal therapeutic approach remains elusive. To ensure a
      more rational design of anti-asthma drugs, recent investigations have attempted
      to elucidate the roles of inflammatory cellular components in asthma. Such
      studies have shown that eosinophilic infiltration is a prominent feature in the
      pathophysiology of asthma. Nonetheless, the role of the eosinophil in asthma has
      been questioned following recent human studies investigating the efficacy of a
      novel therapeutic strategy targeted at eosinophils.

PMID- 12810185
TI  - Bronchial hyperresponsiveness: too complex to be useful?
AB  - Measures of bronchial responsiveness are widely used for the diagnosis and
      monitoring of asthma. A vast array of non-specific bronchoconstrictor stimuli is
      available. Methacholine and histamine cause airflow limitation predominantly
      through a direct effect on airway smooth muscle. Indirect challenges (adenosine,
      exercise and hypertonic saline) induce airflow limitation by an action on cells
      other than smooth muscle cells, with a variety of cells, mediators and receptors
      being involved in this process. Bronchial responsiveness to a direct stimulus is
      only weakly related to airway inflammation, whereas indirect airway challenges
      might better reflect active airway inflammation. Both direct and indirect airway
      challenges are useful outcome parameters in clinical studies of asthma. For
      example, an indirect challenge responds to treatment with inhaled steroids within
      hours to days, whereas improvement in direct responsiveness might take months to
      years. Bronchial challenges are also an essential step in the development of new
      anti-asthma treatments, such as adenosine or tachykinin receptor antagonists.

PMID- 12810186
TI  - Airway sensory innervation as a target for novel therapies: an outdated concept?
AB  - Sensory nerves in the airways regulate central and local reflex events such as
      bronchoconstriction, airway plasma leakage, mucus secretion and cough. Sensory
      nerve activity can be enhanced during inflammation and, as a result, these
      protective reflexes become exacerbated and deleterious. The development of drugs
      that directly inhibit sensory nerve function has again become an attractive
      target for the pharmaceutical industry. In particular, the focus is on inhibition
      of the symptoms associated with airway inflammatory diseases such as asthma,
      chronic obstructive pulmonary disease and cough of any aetiology.

PMID- 12810187
TI  - Modeling asthma and COPD in animals: a pointless exercise?
AB  - Animal modeling has been essential to the development of every drug used to treat
      asthma and chronic obstructive pulmonary disease (COPD). Determining the safety
      and efficacy of new therapeutics will also depend upon animal experimentation,
      and future targets for therapeutic intervention will probably be identified
      during careful experimentation using animals. Animal modeling of chronic diseases
      is made possible by the fact that the processes associated with the regulation of
      breathing, gas exchange, airway smooth-muscle contraction and relaxation, blood
      flow through the pulmonary and bronchial vasculature, inflammatory cell
      recruitment, mucus secretion, mucociliary clearance and airway surface liquid
      composition are highly conserved in mammals. This conservation is apparent at the
      whole-organ level and also at the level of the cell and the genome. The
      subtleties of how the airways and lungs are regulated and experimentally measured
      in different species make the more complex processes associated with asthma and
      COPD difficult to faithfully model or duplicate in mammals, particularly in
      mammals such as rodents that are only distantly related to humans.

PMID- 12810188
TI  - The single mediator approach to asthma therapy: is it so unreasonable?
AB  - Asthma involves a complex syndrome of respiratory pathologies that ultimately
      results in bronchial obstruction and reduced lung ventilatory capacity.
      Inflammation of the respiratory tract underlies this disease and can be linked to
      the production and release of multiple mediators of bronchoconstriction and
      airway wall restructuring and obstruction. Disease triggers vary between patients
      and include allergens, exercise, inhaled irritants and virus infections. Disease
      severity can also be highly variable from patient to patient. All of this
      indicates a heterogeneous disease phenomenon. Bronchodilator drugs that induce
      rapid symptom relief are just one component of conventional asthma therapy. The
      use of controller agents, such as anti-inflammatory glucocorticoids, constitutes
      the other important treatment option. The question is whether a key mediator is
      released in asthma that can be targeted by either single or multiple therapeutic
      agents to halt or reverse this complex mix of disease processes.

PMID- 12810189
TI  - Anti-leukotrienes: here to stay?
AB  - Anti-leukotrienes, which are competitive antagonists of cysteinyl-leukotriene-1
      receptors, are the first new class of anti-asthmatics introduced in over 30
      years. There is a strong scientific rationale for their use, as cysteinyl
      leukotrienes are increased in asthma and can mimic several of the
      pathophysiological features of asthma. In addition, there is often increased
      tissue responsiveness to these mediators. Anti-leukotrienes inhibit several
      bronchoconstrictor challenges, including allergens, exercise, irritants and
      aspirin. In clinical trials, they have significant benefit compared with placebo,
      but are less effective compared with low doses of inhaled corticosteroids. As an
      add-on therapy to inhaled corticosteroids, they are also disappointing and less
      effective than long-acting beta(2)-receptor agonists. In clinical practice, they
      have not proved to be very useful, and they are less cost-effective than other
      treatments. It is unlikely that this class of drug will be improved greatly in
      the future, and so will remain as a weak second-line therapy.

PMID- 12810190
TI  - The case for a role for adenosine in asthma: almost convincing?
AB  - Mice rendered adenosine deaminase-deficient manifest an 'asthma' phenotype in the
      lungs that includes mast cell degranulation, eosinophilia, mucus hypersecretion
      and bronchial hyperresponsiveness. These changes can be reversed by enzyme
      therapy with adenosine deaminase, and attenuated by theophylline. Theophylline
      also blocks the pro-inflammatory effects of adenosine in allergen-challenged
      mice. Adenosine A(2A) receptors are an essential part of the physiological
      negative feedback mechanism for limitation and termination of both tissue
      specific and systemic inflammatory responses. In recent clinical studies,
      increases in plasma adenosine have been shown to accompany exercise-induced
      asthma, and adenosine concentrations in exhaled breath condensate are increased
      in asthmatics. These new data provide support for a key role for adenosine in
      asthma, which has become increasingly persuasive in recent years. The evidence is
      now convincing, and the time has come for the asthma community to give its full
      support to the design and evaluation of molecules that mimic or block the
      biological effects of adenosine as potential novel therapeutics for this
      condition.

PMID- 12810191
TI  - Long-acting beta 2-adrenoceptor agonists or tiotropium bromide for patients with
      COPD: is combination therapy justified?
AB  - Bronchodilators are the mainstay of therapy for patients with established chronic
      obstructive pulmonary disease (COPD) but, at present, the majority of patients
      use short-acting agents. There is increasing evidence that long-acting agents,
      such as the beta(2)-adrenoceptor agonists salmeterol and formeterol, and the new
      anticholinergic tiotropium bromide provide a better therapeutic option. In the
      treatment of COPD, long-acting beta(2)-adrenoceptor agonists (LABAs) given twice
      daily cause the same degree of bronchodilation as tiotropium bromide given once
      daily. Combined use of an inhaled LABA with tiotropium bromide should provide
      important therapeutic benefits, as these drugs have distinct and complementary
      pharmacological actions in the airways. Although clinical trials of this
      combination have not been performed, clinical experience with Combivent, a
      combination of a short-acting beta(2)-adrenoceptor agonist (salbutamol) and a
      short-acting anticholinergic (ipratropium bromide), in COPD is encouraging
      because the bronchodilation produced is of a magnitude greater than that of
      either component alone. However, because LABAs are given twice daily but
      tiotropium bromide is required only once daily, the challenge is to develop a
      combined inhaler that can be employed on a daily basis.

PMID- 12810192
TI  - Musculoskeletal diseases: from complex genetics to therapy.

PMID- 12810193
TI  - Molecular genetics of rheumatoid arthritis.
AB  - Following the successful determination of the molecular genetics of single-gene
      disorders, attention has not surprisingly turned to complex genetic disorders.
      However, preliminary experience suggests that unravelling the genetic component
      of common inflammatory disorders, such as rheumatoid arthritis, multiple
      sclerosis and systemic lupus erythematosus, might be a harder nut to crack.

PMID- 12810194
TI  - Genetic determinants of susceptibility to osteoporosis.
AB  - Major advances in our knowledge about the genetic determinants of osteoporosis
      have been made in recent years. They include the discovery of genes responsible
      for monogenic bone diseases associated with abnormal bone mass; the
      identification of quantitative trait loci for bone mass in the general population
      and in mice; and the characterisation of several candidate genes for
      osteoporosis. Information from these studies is being used to design new drugs
      for osteoporosis and to develop genetic markers for fracture risk assessment.

PMID- 12810195
TI  - Genetics of calcium-sensing--regulation of calcium levels in the body.
AB  - The skeleton contains over 200 bones, with the regulation of calcium being vital
      for maintaining this dynamic tissue. The calcium-sensing receptor (CASR) plays a
      pivotal role in the regulation of calcium both systemically through the
      parathyroid and locally in specific tissues. Recent studies have identified
      several sites of expression and further functions for the CASR gene, which
      include a role in the epidermis, tooth development and fluid regulation. In
      addition, genetic studies have identified gain-of-function mutations in the CASR
      gene, leading to a greater understanding of the pathogenesis of Bartter's
      syndrome, an inherited nephropathy that results in deficiency of sodium and
      chloride absorption.

PMID- 12810196
TI  - Genetics of osteoarthritis and potential for drug development.
AB  - Genome-wide linkage scans for the mapping of osteoarthritis susceptibility loci
      have come to the fore in recent years, driven by the failure of candidate gene
      association studies. Four scans have been published, with several strong linkages
      reported. These do not encompass the major cartilage structural genes that many
      consider the most likely susceptibility loci. This has increased the probability
      that the biological pathways responsible for susceptibility are modifiable by
      drug treatment, which one would not reasonably expect for a structural protein.
      This in itself has stimulated the interest of several pharmaceutical companies.
      Such interest will be to the benefit of patients, but will require candid co
      operation between academics and industry if the delay in transferring research
      findings from the laboratory to the clinic is to be minimised.

PMID- 12810197
TI  - Role of transcription factors in skeletal muscle and the potential for
      pharmacological manipulation.
AB  - Our understanding of the role of transcription factors in skeletal muscle vastly
      exceeds our ability to manipulate this class of proteins for therapeutic benefit.
      Transcription factors responsible for controlling the fate, growth, migration,
      proliferation, differentiation and regeneration of muscle cells have been
      identified, and additional factors involved in these processes continue to be
      discovered. These factors are often involved in multiple steps in muscle
      differentiation and can have redundant activities. As such, a detailed
      understanding of their intermolecular interactions and the gene programs they
      control is essential to the rational design of therapeutics. Mutations in
      transcription factors cause a number of muscle disorders. Moreover, the
      manipulation of transcriptional signals holds the promise of treating muscle
      diseases by exploiting the ability of muscle cells to regenerate after injury.
      Finally, several proteins have recently been shown to inhibit muscular dystrophy
      in mouse models. Because some of these proteins are enriched at the neuromuscular
      synapse, the manipulation of factors governing synaptic transcription is a
      promising new approach to the treatment of muscular dystrophy.

PMID- 12810198
TI  - Expression profiling and pharmacogenomics of muscle and muscle disease.
AB  - Parallel technologies are emerging for the study of DNA (single nucleotide
      polymorphism genotyping and association studies), and RNA (microarrays and
      expression profiling). Muscle tissue has many intrinsic features that make it the
      tissue of choice to model the application of these newly emerging technologies.
      Well-preserved human biopsies are readily available both from volunteers
      undergoing specific muscle training protocols and from neuromuscular disease
      patients. Furthermore, the rapid adaptation of muscle to environmental cues (e.g.
      exercise, conditioning and weightlessness) makes it possible to conduct time
      series data in humans (molecular cause and effect). Muscle is also important in
      drug metabolism and adverse events, and the application of single nucleotide
      polymorphism association studies in muscle pharmacogenomics is a field of
      expected future growth.

PMID- 12810200
TI  - Antibody therapy for rheumatoid arthritis.
AB  - High-quality monoclonal antibodies (mAbs) with specificity for relevant disease
      molecules can now be produced in abundance. Anti-tumour necrosis factor-alpha
      therapies have set a new standard for symptom control in rheumatoid arthritis,
      and blockade of tumour necrosis factor has the potential to protect joints from
      structural damage. Other targets for therapeutic antibodies include the cytokines
      interleukin (IL)-1, IL-6, IL-8, IL-15, IL-17 and IL-18. In addition, there is
      preliminary evidence for the clinical efficacy of both keliximab, a mAb targeting
      the T cell antigen CD4, and rituximab, a chimeric mAb against the B cell antigen
      CD20 and CTLA4-Ig, which blocks the CD28/B7 interaction. Phase III studies have
      yet to be undertaken for these novel biological agents, and it is unclear whether
      any of these agents will have true disease-modifying capabilities.

PMID- 12810199
TI  - The role of apoptosis in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease, which results in
      inflammation of the synovial lining and destruction of the adjacent bone and
      cartilage. Synovial macrophages, fibroblasts and lymphocytes are critical to the
      pathogenesis of this disease, in which apoptosis may play divergent roles. In
      joints of patients with active RA, few apoptotic cells are detected, and
      experimental data suggest that enhanced apoptosis within the joint might be
      therapeutically beneficial. Signaling pathways, such as the nuclear factor kappa
      B, phosphatidylinositol 3-kinase/Akt-1 and signal transducer and activator of
      transcription-3 pathways, are highly activated in the RA joint. Activation of
      these pathways contributes not only to the expression of genes that cause
      inflammation and destruction but also to the expression of a variety of anti
      apoptotic molecules, including FLICE inhibitory protein, Bcl-2, and Mcl-1, which
      protect against apoptosis that may be initiated through death receptor- or
      mitochondria-dependent pathways. The induction of apoptosis of macrophages,
      synovial fibroblasts or lymphocytes, either through suppression of signaling
      pathways or inhibition of the expression of anti-apoptotic molecules, could be
      therapeutically beneficial in RA. While tumour necrosis factor-alpha contributes
      to inflammation, destruction and protection against apoptosis in the RA joint
      (together with FasL), it also promotes apoptosis of bone marrow progenitor cells
      that contribute to anemia of chronic disease, which is very common in acute RA.

PMID- 12810201
TI  - Stem cells in the treatment of muscle and connective tissue diseases.
AB  - Current data indicate the existence of two types of postnatal stem cells. Tissue
      non-specific stem cells are haematopoietic in origin and can differentiate into
      different blood lineages. In contrast, tissue-specific stem cells preferentially
      differentiate into cells of the residing tissue, although they also possess a
      limited ability to turn into other lineages. In terms of therapeutic potential,
      unmodified muscle-derived stem cells have been proven capable of regenerating
      dystrophic muscle. Furthermore, when genetically modified to express growth
      factors, these cells are versatile in promoting bone healing. This also occurs
      with mesenchymal stem cells, which have been used in an attempt to repair defects
      of cartilage and ligaments. Thus, stem-cell-based therapy--particularly
      genetically engineered therapy--holds great potential for the treatment of a
      variety of disorders and conditions affecting the muscle and connective tissue.

PMID- 12810202
TI  - A cost-outcome analysis of long-term adjuvant goserelin in addition to
      radiotherapy for locally advanced prostate cancer.
AB  - To quantify the incremental costs and outcomes of using long-term adjuvant
      goserelin in addition to radiotherapy for locally advanced prostate cancer. The
      cost of radiotherapy for prostate cancer has been calculated using an activity
      costing model. The total cost of administering adjuvant hormonal therapy for 3
      years is based on local pharmacy charges plus typical physician billing fees and
      additional laboratory costs. Outcome data were obtained from the published EORTC
      22,863 randomized trial comparing treatment of locally advanced prostate cancer
      with radiotherapy alone or in combination with 3 years of adjuvant goserelin.
      Using this information, the cost-effectiveness of adjuvant goserelin was
      calculated and expressed in terms of dollars per life-years (LY) gained. The
      total institutional costs of radiotherapy are $9000 Cdn. and the additional costs
      of providing adjuvant goserelin for 3 years are approximately $19,800 CDN. The
      improvement in outcome with the use of adjuvant goserelin was estimated to be 1.2
      LY per patient treated, giving a cost-effectiveness ratio of $16,500 Cdn ($11,000
      US) per LY from an institutional perspective. Our sensitivity analysis confirms
      the robustness of our findings since even in our "worst case" scenario the cost
      effectiveness ratio was estimated to be $21,600 Can ($14,400 US) per LY gained.
      This figure is still below $50,000 US per LY gained which is the quoted current
      standard for cost-effectiveness. This analysis demonstrates that the use of long
      term adjuvant goserelin for locally advanced prostate cancer provides substantial
      benefit at an acceptable cost.

PMID- 12810203
TI  - Conventional (clear cell) renal carcinoma metastases have greater bcl-2
      expression than high-risk primary tumors.
AB  - Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In
      renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its
      expression is reportedly low in primary tumors and lacks prognostic value. This
      study evaluates patterns of bcl-2 expression in high-risk (pT(3)) primary tumors
      and in matched patient metastases. Immunohistochemical analysis of bcl-2 was
      performed on 149 cases of conventional (clear cell) RCC (112 pT(3) primaries, 37
      metastases). Paraffin-embedded tissues were obtained from nephrectomies and
      metastatic resections. Median follow up was 48 months in the entire cohort and 69
      months in living patients. We evaluated associations between bcl-2 expression and
      tumor recurrence or patient survival with the Cox regression test, and used the t
      test and Pearson correlation methods to evaluate bcl-2 expression in primary and
      metastatic cases. Bcl-2 expression was observed at a higher frequency in
      metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P <
      0.001). The percentage of cells stained was greater in metastases than primary
      tumors (P = 0.003). This finding was also noted when expression in metastatic
      cases was compared with matched primaries (P = 0.05). Bcl-2 expression did not
      predict disease-free (P = 0.30), disease-specific (P = 0.90), or overall (P =
      0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2
      protein, whereas most RCC metastases display greater protein levels. Bcl-2
      expression in primary tumors does not predict clinical outcome. However,
      expression of bcl-2 protein occurs at a high frequency in RCC metastases when
      compared to primary tumors. It may be reasonable to target RCC patients
      displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2,
      should metastatic disease develop.

PMID- 12810204
TI  - Phase II trial of cisplatin, 5-fluorouracil, and interferon-alpha-2B as first
      line treatment of advanced urothelial cancer.
AB  - Cisplatin based combination chemotherapy remains the mainstay for treatment of
      advanced urothelial cancer. The combination of 5-fluorouracil and interferon has
      been found to be effective second line treatment of advanced urothelial cancer.
      Hence, we tested the combination of cisplatin, 5-fluorouracil and interferon as
      first line therapy in advanced urothelial cancer. Eligible patients had to have
      no prior chemotherapy or interferon. Treatment consisted of cisplatin 80 mg/m(2)
      on day one, followed by 5-fluorouracil 750 mg/m(2) as a daily infusion for 5 days
      and interferon alpha 2 B 5 MU/m(2) subcutaneously daily on day 1-5 of 5
      fluorouracil infusion. Cycles repeated every 21 days. Eighteen patients, of which
      sixteen were males were enrolled. Median age was 60 years. All patients had
      transitional-cell carcinoma. The median number of cycles given was 4. Thirteen
      patients were evaluable for response. Two patients achieved CR and 3 PR for an
      overall response rate of 28% (95% confidence interval 7% to 49%). Median response
      duration was 8.3 months. Median survival was 5.5 months. Four patients died
      secondary to chemotherapy toxicities. Those were GI perforation in one,
      bronchopneumonia in one, acute renal failure in one and one patient died at home
      3 weeks following the third cycle. The above regimen demonstrates excessive
      toxicity and moderate activity. It cannot be recommended in its present format.
      Novel anti-cancer agents need to explored.

PMID- 12810205
TI  - Caveolin expression in adult renal tumors.
AB  - Histopathological criteria are usually sufficient for the accurate distinction of
      benign form malignant renal tumors. A minority of cases however, poses a vexing
      diagnostic dilemma. Recent studies suggest that caveolin, a scaffolding cell
      membrane protein may prove helpful in predicting the behavior of these neoplasms.
      We analyzed a series of 40 renal tumors of which 7 were clear cell and 6 granular
      Renal Cell Carcinomas (RCC), 10 cases of Papillary Carcinoma (PCC), 4 cases of
      Chromophobe Renal cell carcinomas (CRCR), 11 cases of Oncocytomas (OC) and 2
      cases of Collecting Duct Carcinomas (CDC). The distribution of immunoreactivity
      was analyzed by quantifying caveolin cell membrane staining in each case. There
      was a statistically significant difference in the expression of caveolin-1
      between oncocytoma with a mean labeling index of 91.7 and the cases of malignant
      renal tumors with a mean labeling index of 26.9 for RCC, 24 for CDC, 21 for CRCR,
      and 19.2 for PCC. The results suggest an association between loss of caveolin
      expression among malignant renal tumors that might be useful in distinguishing
      oncocytoma from malignant renal tumors and possibly implicates this peptide in
      their pathogenesis.

PMID- 12810206
TI  - Combination of adenovirus-mediated thymidine kinase gene therapy with cytotoxic
      chemotherapy in bladder cancer in vitro.
AB  - We evaluated efficacy, toxicity and potential synergism of adenoviral-mediated
      thymidine kinase (tk)- ganciclovir (GCV) gene therapy in combination with 4
      cytotoxic chemotherapeutic agents (doxorubicin, cisplatin, mitomycin C, and
      methotrexate) in 3 human bladder cancer cell lines. Cell lines were exposed to
      (1) 10 different concentrations of adenovirus expressing tk plus GCV; (2) 8
      different concentrations of either doxorubicin, methotrexate, mitomycin C or
      cisplatin; or (3) combination treatment consisting of either low-, medium- or
      high-dose tk-GCV gene therapy plus 8 different concentrations of a single
      chemotherapeutic agent. Cell survival was determined using a MTT-based cell
      proliferation-assay. For most combinations, adding chemotherapy to tk-GCV gene
      therapy did not result in any therapeutic benefit. In some scenarios, we observed
      modest improvement with combinations of high-dose tk-GCV gene therapy and high
      dose standard chemotherapy over tk-GCV monotherapy. Low concentrations of
      methotrexate enhanced the antitumor effects of low- and medium-dose tk-GCV gene
      therapy. Low level negative interference between tk-GCV gene therapy and
      chemotherapy occurred in some combinations but was overall negligible. In
      general, adding chemotherapy to tk-GCV gene therapy did not demonstrate
      significant therapeutic benefit in vitro. High doses of chemotherapeutic agents
      should be used in combination with tk-GCV gene therapy in order to take advantage
      of the occasional instance where modest improvement occurred with combination
      therapy. Additional studies exploring the role of methotrexate in enhancing the
      tk-GCV system are required. Investigation of other, potentially more synergistic
      chemotherapeutic agents in combination with tk-GCV is warranted.

PMID- 12810207
TI  - Is bladder biopsy necessary at three or six months post BCG therapy?
AB  - The standard of practice set by the SWOG investigation of BCG therapy for
      superficial bladder cancer has been to evaluate response at 3 months with
      cystoscopy and bladder biopsy. This study is to determine if all patients require
      a biopsy post therapy at 3 or 6 months. We reviewed the charts of 43 patients who
      had received a 6-weekly course of BCG (Connaught strain) for high grade or
      recurrent Ta, T1, or Tis transitional cell carcinoma of the bladder. The patients
      with Ta recurrent, T1 or Tis disease received maintenance therapy. All patients
      were followed through 6 months. At 3 months, 32/43 patients had negative
      cystoscopies. All 32 patients had corresponding negative biopsies. Eight patients
      had visible papillary tumors, while three patients had erythematous lesions,
      which were biopsy negative. At 6 months, eight different patients had visible
      lesions on cystoscopy that were biopsy proven superficial bladder cancer. The
      positive predictive value at 3 and 6 months post BCG therapy was 72.6% and 100%,
      respectively. The false positive rate was 7% at the 3-month checkpoint. Bladder
      biopsy is not necessary at the 3 or 6 month period following BCG therapy in the
      face of negative cystoscopic findings.

PMID- 12810209
TI  - Contemporary preoperative parameters predict cancer-free survival after radical
      prostatectomy: a tool to facilitate treatment decisions.
AB  - Prostate specific antigen (PSA) screening has heralded stage migration in
      prostate cancer toward cancers that may be readily eliminated by primary
      intervention. We sought to identify contemporary, preprostatectomy measures of
      cancer severity useful and significant for predicting postprostatectomy,
      recurrence-free survival. The association of baseline variables clinical
      variables (age, clinical stage, serum PSA, and race) and prostate biopsy
      parameters (Gleason score, presence of perineural invasion, number of biopsy
      cores with cancer, and the greatest percentage of a biopsy core occupied by
      cancer--GPC) with recurrence-free survival was evaluated by multivariate Cox
      proportional hazards regression among consecutive patients that underwent radical
      prostatectomy as primary therapy between 1994 and 2002. Tables were generated
      depicting expected 5-year recurrence-free survival after prostatectomy. From 1414
      patients, 183 developed biochemical recurrence, 8 died from prostate cancer, and
      31 died of all causes. Multivariable Cox regression found that clinical stage,
      PSA, Gleason score, and the greatest percentage of a biopsy core involved by
      cancer (GPC), were each significant determinants of post-prostatectomy, PSA
      recurrence-free survival (P < 0.05 for each). Gleason score and GPC were also
      significantly associated with clinical recurrence-free survival and cancer death,
      whereas other biopsy parameters and PSA were not. The amount of cancer in a
      biopsy core is a significant predictor of recurrence-free survival after
      prostatectomy, and is a simple clinical measure that complements baseline PSA,
      and Gleason score in predicting outcome. Tabulated 5-year PSA-free survival
      outcomes, stratified by these preoperative parameters, provide a basis for
      preoperative counseling of patients regarding postprostatectomy cancer control
      expectations.

PMID- 12810210
TI  - High-risk localized prostate cancer: primary surgery and adjuvant therapy.
AB  - High risk localized prostate cancer includes patients with palpable disease
      outside the capsule (clinical stage T3) as well as those with apparently
      localized disease but with adverse prognostic factors such as Gleason 8-10 tumors
      or very extensive disease on biopsy. The goals of therapy for these patients are
      to achieve both long-term local control and to remain free of metastatic disease.
      The ideal treatment to achieve these goals is unknown. We present a review of the
      outcome of contemporary reported series of such patients treated with primary
      radical prostatectomy, with or without neoadjuvant or adjuvant therapies. Over
      80% of the patients overall achieved a 5-year disease-specific survival, though
      well under 50% have undetectable prostate specific antigen at that time point. We
      also review what is known about the choice and timing of adjuvant therapies, and
      describe current cooperative group studies underway to answer some of these
      questions.

PMID- 12810211
TI  - Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate
      cancer: defining appropriate endpoints.
AB  - High-risk localized prostate cancer remains a vexing problem for clinicians.
      Definitive local treatments such as surgery and radiation therapy cure only a
      minority of these patients. As a result, efforts are being made to reduce the
      risk of recurrence by using chemotherapy and new agents before, during or after
      definitive local therapy. Neoadjuvant androgen deprivation therapy has yielded
      disappointing results when combined with surgery. Chemotherapy in the management
      of localized disease is evolving, and preliminary studies are just now being
      completed. Although these agents have established activity and acceptable
      toxicity in the hormone-refractory setting, more extensive use of them in
      patients with androgen-dependent disease will require data from randomized
      studies to determine overall efficacy. New molecular-targeted therapies are
      promising and hold the greatest hope that outcomes in early disease may be
      improved with early use of systemic therapy. The neoadjuvant surgical model also
      has promise in assessing the activity of new drugs, because it provides a means
      to determine molecular effects of specific agents, along with standard pathologic
      and clinical parameters of efficacy.

PMID- 12810212
TI  - Management of high-risk localized prostate cancer: the integration of local and
      systemic therapy approaches.
AB  - Using a combination of PSA, Gleason score, and clinical stage, it is possible to
      identify a group of patients with prostate cancer who have a high risk of relapse
      following initial treatment (e.g., radiotherapy or radical prostatectomy). For
      these patients, multi-modal therapy may result in improved outcomes. We reviewed
      published literature to identify methods to identify high-risk patients as well
      as options for adjuvant or neoadjuvant therapy to reduce risk of disease
      recurrence. At the present time, the most promising adjuvant therapy is hormonal
      therapy following radiotherapy for locally advanced disease (T3-T4, or N1). In
      phase III trials in these patients, survival is improved. For all other
      applications, including adjuvant and neoadjuvant hormonal therapy, chemotherapy,
      or radiotherapy, the benefits are unclear. Perhaps most promising at this time,
      and the subject of a current phase III trial, is the utility of adjuvant
      chemotherapy in high-risk patients. It will be through the conduct of phase III
      trials that the benefits of multi-modal therapy will be evaluated. Patients with
      high-risk prostate cancer undergoing radiotherapy or surgery should be offered
      participation in these clinical trials.

PMID- 12810213
TI  - Magnetic resonance imaging in the assessment of synovial inflammation of the
      hindfoot in patients with rheumatoid arthritis and other polyarthritis.
AB  - OBJECTIVES: To describe the localisation of synovitis and tenosynovitis of the
      hindfoot observed on magnetic resonance imaging (MRI) in patients with chronic
      polyarthritis, and to correlate the findings of physical examination and MRI.
      METHODS: Patients with chronic polyarthritis, and one or two painful hindfoot
      were included. On physical examination and on MRI, the tibio-talar, talo
      calcaneal, and talo-navicular and calcaneo-cuboidal joints were adjudged to have
      or not synovitis, and the tibialis anterior and posterior, the peroneus longus
      and brevis, the flector digitorum and hallucis longus tendons to have or not
      tenosynovitis. Criteria for synovitis and tenosynovitis were a high signal
      intensity on T2-weighted images, a low signal intensity on T1-weighted images,
      and enhancement after Gd-DTPA injection, in the joint area, and around the
      tendon, respectively. The correlation between the findings of physical
      examination and those of MRI were evaluated using the Kappa statistics. RESULTS:
      12 patients (three men, nine women, mean age of 55.5 years+/-11.4 S.D.) with
      chronic polyarthritis (rheumatoid arthritis (RA): nine, ankylosing spondylitis:
      one; psoriatic arthritis: one, unclassified: one) were included. All presented
      with one (7 patients) or two (5 patients) painful hindfeet (and swelling for 16
      out of 17 hindfeet). On physical examination, 25 joints and eight tendons were
      adjudged to have synovitis and tenosynovitis. MRI showed synovitis in 12 out of
      25 of these joints (48%), and tenosynovotis in three out of eight of these
      tendons (37.5%). Moreover, MRI showed ten and seven clinically unsuspected
      synovitis and tenosynovitis, respectively. The proportion of agreements between
      physical examination and MRI were 54.9% (kappa=0.1) and 88.2% (kappa=0.27) for
      synovitis and tenosynovitis, respectively. CONCLUSION: A weak correlation was
      observed between the findings of physical examination and MRI in patients with
      chronic polyarthritis and a painful hindfoot. MRI might be used to localise
      synovitis in the area before performing some intra-articular injections. However,
      other studies are needed to address this question.

PMID- 12810214
TI  - Incidentally found and unexpected tumors discovered by MRI examination for
      temporomandibular joint arthrosis.
AB  - We examined the frequency of incidentally found or unexpected tumors discovered
      at the time of magnetic resonance imaging (MRI) examinations in the
      temporomandibular joint (TMJ) region for patients with suspicion of TMJ
      arthrosis. Five MR images (T1-weighted transverse scout image and proton density
      and T2-weighted oblique sagittal images at the open and closed mouth) were
      acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered.
      They consisted of an adenoid cystic carcinoma in the deep portion of the parotid
      gland, and a malignant tumor extending from the infratemporal fossa to the
      parapharyngeal space. The rate of incidentally founded or unexpected tumors in
      TMJ examinations was low (0.072%), but the two tumors found were malignant
      tumors, and therefore, scout image should be carefully examined, not only used
      for positing the slice.

PMID- 12810215
TI  - Meniscal tears: comparison of half-Fourier technique and conventional MR imaging.
AB  - PURPOSE: To determine whether half-Fourier MR image acquisition technique can
      provide similar information to that of conventional MR acquisition technique for
      evaluation of meniscal tears. MATERIALS AND METHODS: We studied 101 menisci in 52
      patients who were referred for evaluation of meniscal tears. Sagittal MR images
      of the knee were obtained for all patients by using proton density and T2
      weighted SE sequences on a 1-T clinical system. The half-Fourier technique and
      conventional technique were used for all patients. All other imaging parameters
      were identical for both sequences (TR/TE=2400/20,70; 3 mm slice thickness; 200 x
      256 matrix; field of view, 200; one signal acquired). Both sets of images were
      filmed with standard window and level settings. Images were randomised and
      interpreted independently by two radiologists for the presence of meniscal tears.
      Images were also subjectively assessed for image quality using a five-point
      grading scale. RESULTS: On half-Fourier images, Reader 1 interpreted 23 menisci
      as torn, compared to 28 for Reader 2. On conventional images, Reader 1
      interpreted 24 menisci as torn, compared to 26 for Reader 2. Agreement between
      interpretation of the conventional and that of the half-Fourier images was 99%
      for Reader 1, and 98% for Reader 2. Agreement between readers for the half
      Fourier images was 95%, and for the conventional images 96%. No statistically
      significant difference was found in the subjective evaluation of image quality
      between the conventional and half-Fourier images. CONCLUSION: The half-Fourier
      acquisition technique compares favourably with the conventional technique for the
      evaluation of meniscal tears.

PMID- 12810216
TI  - Quiz case. Macrodystrophia lipomatosa.

PMID- 12810217
TI  - Osteogenesis imperfecta in childhood: MR imaging of basilar impression.
AB  - OBJECTIVE: To determine on radiographs the presence of Basilar Impression (BI) in
      children with Osteogenesis Imperfecta (OI). To confirm this sign and altered
      geometrical relationships of the craniocervical junction in course of time with
      magnetic resonance imaging (MRI). METHODS AND PATIENTS: In a cohort study of 130
      patients with OI (OI type I: 85; OI type III: 21; OI type IV: 24) lateral
      radiographs of the skull and cervical spine were made in a standardised way. MRI
      scans were performed when BI was suspected based upon protrusion of the odontoid
      above Chamberlain's line. Intracranial abnormalities as well as the basal angle
      were described. Neurological examination was performed in patients with
      conclusive BI at MRI-scan. RESULTS AND DISCUSSION: In eight patients BI could be
      confirmed by MRI-scan. None of the children had or developed in time neurological
      symptoms or signs. Follow up of BI by MRI scans was done in seven patients (mean:
      5 years; range: 2-6 years). No alteration of intracranial findings were seen at
      subsequent investigation, although in one child Chamberlain's line increased from
      8 (first MRI) to 15 mm (last MRI). BI can be diagnosed by radiographs but in the
      extreme osteoporotic bone and altered anatomy of the craniocervical junction of
      children with OI MRI is preferable. As intracranial pathology can be demonstrated
      by MRI, also a relation can be laid to possible neurological symptoms and signs
      at clinical examination. CONCLUSION: In our cohort study no alteration of the
      intracranial contents was seen at subsequent MRI scans. Although anatomic
      deformations exist in BI, no neurological symptoms or signs were present in our
      study and no operative reconstruction had to be performed. Periodical MRI-scan
      has not been of influence on the clinical decision making process. At the moment
      we perform a MRI-scan if BI is suspected at lateral skull radiographs. The MRI
      images serve as reference findings to anticipate on possible future symptoms and
      signs of neurological deficit.

PMID- 12810218
TI  - Can bone marrow edema be seen on STIR images of the ankle and foot after 1 week
      of running?
AB  - PURPOSE: To evaluate whether initiation of running in sedentary individuals would
      lead to bone marrow edema on MR images, within the time span of 1 week. MATERIALS
      AND METHODS: The feet of 10 healthy volunteers were imaged by MR imaging before
      and after running during 30 min a day for 1 week. The images were evaluated by
      consensus of 2 musculoskeletal radiologists who graded the presence of bone
      marrow edema on a 4-point scale. Edema scores and number of bones involved before
      and after running were compared statistically. RESULTS: Edema was present on the
      baseline images in 3 subjects. After running edema showed an increase or was
      present in 5 subjects. The changes after running were statistically significant.
      Bones involved were the talus, calcaneus, navicular bone, cuboid bone, and 5th
      metatarsal. CONCLUSION: Edema patterns can be seen in the feet of asymptomatic
      individuals. During initiation of running an increase of edema or development of
      new edema areas can be seen.

PMID- 12810219
TI  - Spiral CT and radiation dose.
AB  - Recent studies in the USA and Europe state that computed tomography (CT) scans
      compromise only 3-5% of all radiological exams, but they contribute 35-45% of
      total radiation dose to the patient population. These studies lead to concern by
      several public authorities. Basis of CT-dose measurements is the computed
      tomography dose index (CTDI), which was established 1981. Nowadays there are
      several modifications of the CTDI values, which may lead to confusion. It is
      suggested to use the standardized CTDI-100 w. value together with the dose length
      product in all CT-examinations. These values should be printed on all CT-images
      and allows an evaluation of the individualized patient dose. Nowadays,
      radiologist's aim must be to work at the lowest maximal diagnostic acceptable
      signal to noise ratio. To decrease radiation dose radiologist should use low kV
      and mA, but high pitches. Newly developed CT-dose-reduction soft-wares and
      filters should be installed in all CT-machines. We should critically compare the
      average dose used for a specific examination with the reference dose used in this
      country and/or Europe. Greater differences should caution the radiologist.
      Finally, we as radiologists must check very carefully all indications and
      recommend alternative imaging methods. But we have also to teach our customers
      patients and medical doctors who are non-radiologists-that a 'good' image is not
      that which show all possible information, but that which visualize 'only' the
      diagnostic necessary information.

PMID- 12810220
TI  - The measurement of the rotational deformities with computed tomography in femoral
      shaft fractures of the children treated with early spica cast.
AB  - Twenty-eight children with femoral shaft fractures, treated with early spica
      cast, were evaluated with computed tomography (CT), for their femoral shaft
      rotational deformities. The femoral torsion angles were measured on both sides.
      If the torsion angle of the fractured side was more than the other side, it was
      considered as an internal rotational deformity and if it was less, it was
      considered as an external rotational deformity. Internal rotational deformities
      were detected in nine cases and external rotational deformities were detected in
      17 cases. Rotational deformity was not observed in two cases. Four cases, with a
      rotational deformity more than 10 degrees, were corrected with a gypsotomy
      through the level of the fracture. We concluded that a rotational deformity,
      which is an important complication in conservative treatment of the femoral shaft
      fractures in children, can be determined exactly with CT and corrections on the
      spica cast can be made with a gypsotomy.

PMID- 12810221
TI  - Comparison of surface coil and knee coil for evaluation of the patellar cartilage
      by MR imaging.
AB  - PURPOSE: The aim of this work was to compare the knee coil and the surface coil
      for the visualisation of the patellar cartilage. MATERIALS AND METHODS: In 28
      patients (17 women, 11 men) with an average age of 40 years (range 14-76) with
      knee pain MR was performed. Transverse images were obtained using a fast spin
      echo proton density weighted sequence on a Philips Gyroscan Intera 1.5 T clinical
      system. Transverse images were obtained at the level of the patellar cartilage
      using both the surface and the knee coil. All images were evaluated by consensus
      of two radiologists. They evaluated a number of quality criteria on a 4-point
      scale. Criteria for artefacts were also graded on a 4-point scale. RESULTS: For
      the visualisation of fluid there was no significant difference between the knee
      coil and the surface coil (P=0.021). For all other criteria regarding image
      quality and presence of imaging artefacts there was a significant difference
      between both coils (P<0.001) with the surface coil obtaining the better result.
      CONCLUSION: The use of the surface coil in the visualisation of the patellar
      cartilage can be recommended at knee MR.

PMID- 12810222
TI  - Semi-automated evaluation of the cortico-medullar index on radius radiographs: a
      study in prepubertal girls.
AB  - The aim of the study was to validate a non-invasive method allowing a semi
      automatic cortico-medullar index (CMI) computation from standard radiographs.
      Fifty-five radiographs of the non-dominant radius of prepubertal girls (aged
      10.12+/-1.47 years) were scanned (100 microm scanning resolution) by the same
      observer. To detect the grey level peaks, we used the Deriche's recursive filter
      applied to the grey level gradients and we defined the cortical areas by
      thresholding (iterative contour detection). The CMI was calculated as cortical
      areas divided by the total bone area. The reproducibility was tested through the
      analysis of ten radiographs scanned twice, on 5, 10, 15, 20, 30 and 40 lines at
      each side of a reference line located at the distal third part of the radius. We
      used the root mean square coefficient of variation (RMS-CV) as verification. Dual
      Energy X-ray (DXA) was used for densitometry measurements of the whole body, and
      non dominant radius (mid-, distal third and ultra distal). The result attaining
      the best reproducibility concerned the 15-line position (Mean CMI=0.58+/-0.005
      with a 1.36% RMS-CV). CMI correlated significantly with Bone Mineral Density
      (BMD) (r=0.40, 0.33 and 0.50, P<0.01, respectively, at the whole body, mid- and
      third distal of the radius), Bone Mineral Content (BMC) (r=0.32, 0.36, 0.34 and
      0.35, respectively, at the whole body (P=0.01), mid- (P=0.007), third distal
      (P=0.01) and ultra distal of the radius (P=0.01)) but not with BMD at the ultra
      distal of the radius (r=-0.01, P=0.9). This semi-automated new method has been
      easily implemented, reproducible, and therefore, could be useful tool for the
      bone CMI computation.

PMID- 12810223
TI  - Quiz case. Nodular fasciitis.

PMID- 12810224
TI  - Quiz case. Nontraumatic avulsion of the lesser trochanter secondary to metastatic
      adenocarcinoma of the colon.

PMID- 12810225
TI  - Quiz case. Bilateral complex skewfoot.

PMID- 12810226
TI  - Imaging of fractures of the lateral process of the talus, a frequently missed
      diagnosis.
AB  - Although if fractures of the lateral process of the talus (LPT) have been
      considered rare the widespread diffusion in snowboard practice has resulted in a
      dramatic increase in their frequency. If unrecognized they can result in
      secondary osteoarthritis of the ankle and/or talo-calcaneal joints and chronic
      pain and stiffness. Due to the complex anatomy of the region, these fractures are
      difficult to detect by standard radiographs. A high degree of suspicion is then
      necessary to diagnose them. Once suspected on the basis of physical examination
      and/or non concluding radiographs, computed tomography (CT) is the best modality
      to confirm the diagnosis and accurately appreciate the number of the fragments
      and their position which have therapeutic consequences (medical vs. surgical
      treatment). A better knowledge of these lesions seems necessary to the general
      radiologist to allow an early diagnosis in order to avoid chronic sequel. The
      purpose of this article is to report three additional cases of LPT fractures and
      discuss their pathogenesis, diagnosis and treatment.

PMID- 12810227
TI  - Lung findings on high resolution CT in early ankylosing spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly
      affecting the axial skeleton and pulmonary involvement is a well known feature of
      the disease. The aim of this study was to investigate the pulmonary high
      resolution computed tomography (HRCT) findings of patients with early AS. The
      relationship between pulmonary function tests (PFT) and HRCT findings was also
      determined. SUBJECTS AND METHODS: Twenty-eight patients with AS (mean age 30.8+/
      7.4 and disease duration 7.0+/-2.6) were included in the study. Patients with a
      disease duration of >10 years or had other pulmonary diseases were excluded. All
      patients underwent plain chest radiography (posteroanterior and lateral views),
      thoracic HRCT and PFT. RESULTS: All chest radiographs were normal and HRCT
      revealed abnormalities in 18 patients. The most common abnormalities seen on HRCT
      were mosaic pattern (ten of 28), subpleural nodule (seven of 28) and parenchymal
      bands (five of 28). Seven of ten patients with mosaic pattern revealed air
      trapping areas on end expiratory scans. Twelve patients had abnormal PFT and all
      had restrictive type of involvement. Ten of these 12 patients had abnormal HRCT
      and the remaining two patients had normal HRCT. On the other hand, eight patients
      with normal PFT had abnormalities on HRCT. CONCLUSION: Patients with early AS
      frequently have abnormalities on HRCT, even though they have normal PFT and chest
      X-ray. Small airway involvement was found as frequent as interstitial lung
      disease in early AS.

PMID- 12810239
TI  - Prognostic value of QT interval parameters in type 2 diabetes mellitus: results
      of a long-term follow-up prospective study.
AB  - The prognostic importance of electrocardiographic ventricular repolarization QT
      parameters (maximum rate-corrected QT interval-QTcmax, QT interval dispersion
      QTd, and QTcd), in relation to other risk markers, on cardiovascular and cardiac
      mortality, and on total fatal or nonfatal cardiovascular events, was evaluated
      prospectively in 471 type 2 diabetic outpatients. During a median follow-up of 57
      months (range: 2-84), 121 (25.7%), patients died, 44 (36.3% of them) from
      cardiovascular causes and 106 (22.5%) fatal or nonfatal cardiovascular events
      were observed. In Cox proportional hazards multivariate analysis, both QTd and
      QTcmax were independent predictors of cardiovascular and cardiac mortality
      (hazard ratio [HR]: 1.34, 95% confidence interval [95% CI]: 1.12-1.59, for each
      10-ms increments in QTd and HR: 1.17, 95% CI: 1.03-1.21 for 10-ms increments in
      QTcmax, for cardiovascular mortality). They were also predictors of total fatal
      or nonfatal cardiac and cardiovascular events (HR: 1.18, 95% CI: 1.05-1.33 for
      QTd and HR: 1.09, 95% CI: 1.04-1.15 for QTcmax). Additional independent
      prognostic markers for total cardiovascular events were the presence of previous
      cardiac disease, cerebral or peripheral vascular disease, age, male gender, known
      diabetes duration, heart rate, and serum triglycerides. Excluding patients with
      prior cardiac disease did not change significantly the prognostic performance of
      QTd but decreased that of QTcmax. In conclusion, QT interval parameters give
      additional prognostic information in patients with type 2 diabetes mellitus,
      beyond that obtained from traditional risk factors. QT interval dispersion seems
      a better prognostic marker than maximum QT interval, particularly in patients
      without previous cardiac diseases.

PMID- 12810240
TI  - Efficacy and tolerability of acarbose in Asian patients with type 2 diabetes
      inadequately controlled with diet and sulfonylureas.
AB  - The objective of this study was to investigate the efficacy, tolerability, and
      safety of acarbose in the improvement of glycemic control in Asian patients with
      type 2 diabetes inadequately controlled by diet and sulfonylureas. A 24-week,
      double-blind, placebo-controlled multicenter group comparison study was
      conducted. Patients were randomized to receive acarbose titrated up to 100-mg tid
      (n=36) or matching placebo (n=33). Concomitant sulfonylurea treatment remained
      unchanged throughout the study. The primary efficacy parameter was the change in
      HbA(1c) from baseline to double-blind endpoint. Secondary efficacy variables
      consisted of the change from baseline to endpoint in blood glucose (fasting and 1
      h postprandial), serum insulin (fasting and 1-h postprandial), and urinary
      glucose. In the intention-to-treat (ITT) analysis, acarbose treatment was
      associated with significantly greater reductions in glycated hemoglobin (HbA(1c))
      (-0.91% vs. placebo 0.13%, P=.0018) and 1-h postprandial blood glucose levels (
      2.84 mmol/l vs. placebo -0.28 mmol/l, P=.002) compared to placebo. There were no
      significant differences between the treatment groups regarding changes in fasting
      blood glucose, fasting or 1-h postprandial serum insulin, urinary glucose, or
      body weight. Adverse events occurred with similar frequency in both treatment
      arms except for drug-related gastrointestinal side-effects associated with
      acarbose (acarbose 48.5% and placebo 12.5%). This study has shown that the use of
      acarbose in Asian patients with type 2 diabetes inadequately controlled by diet
      and sulfonylureas is efficacious in improving metabolic control and that acarbose
      is safe and well tolerated.

PMID- 12810241
TI  - Risk factor management in stable, insulin-treated patients with Type 2 diabetes:
      the Diabetes Outcomes in Veterans Study.
AB  - OBJECTIVES: Describe the methodologies and study population of the Diabetes
      Outcomes in Veterans Study (DOVES). RESEARCH DESIGN AND METHODS: Prospective,
      multicenter, observational study of Southwestern veterans with stable, insulin
      treated Type 2 diabetes. Subjects were randomly selected from pharmacy records
      and were required to be using at least one long-acting insulin preparation daily.
      Baseline psychosocial evaluations included psychological status, social and
      cultural barriers to care, self-care behaviors, and vascular disease risk
      factors. Clinical measurements included self-reported vascular disease,
      hemoglobin A1c (HbA1c), blood pressure, blood lipids, and body mass index (BMI).
      A subset of subjects completed a protocol of four times daily self-monitored
      blood glucose testing for 8 weeks. Subjects were followed for 12 months.
      Principal endpoints included glycemic control, the occurrence of hypoglycemia,
      and control of vascular disease risk factors. RESULTS: We enrolled 338 subjects.
      The mean (+/-S.D.) age was 65.1+/-9.7 years and 3.8% were women. At baseline,
      over two-thirds of subjects reported vascular disease complications. Nearly three
      quarters had limited physical activity. Among subjects younger than 65 years, 53%
      considered themselves disabled for work. Despite the high prevalence of vascular
      disease, 43.8% had an HbA1c >/=8.0%. Many subjects were sedentary, 62.1% had a
      BMI of 30 kg/m(2) or above, and 22.2% were still smoking. CONCLUSIONS: Detailed
      measurements of psychological status, self-care behaviors, and risk factor
      control are feasible in this elderly, debilitated population. Although the
      prevalence of complications and self-rated disability was high, vascular disease
      risk factors were poorly controlled in a substantial proportion of subjects.

PMID- 12810242
TI  - Oral dryness and peripheral neuropathy in subjects with type 2 diabetes.
AB  - Two common complaints related to diabetes mellitus are oral dryness (xerostomia)
      and peripheral neuropathy (PN) and there is some evidence of a relationship
      between them. Therefore, we formulated a hypothesis that type 2 diabetic subjects
      with xerostomia in our study also exhibited PN. The study included 102 randomly
      sampled type 2 diabetic patients from a healthcare district in mid-Sweden.
      Besides clinical and X-ray examinations, patients were asked whether they
      experienced oral dryness. PN was defined through thorough foot examination and
      the use of a modified neuropathy symptom score (NSS) and neuropathy disability
      score (NDS). Other diabetes-related variables were extracted from medical
      records. More than half of the individuals (53.5%) reported oral dryness and
      23.8% were diagnosed with PN. None of the variables in a stepwise regression
      analysis could explain the variance in oral dryness, besides "pain in the legs,"
      which contributed with 5% to the explanation. Our hypothesis that type 2 diabetic
      subjects with xerostomia also were affected with PN could not be verified in this
      study, but the results must be interpreted with caution as relatively few
      subjects were affected with both oral dryness and PN (13.8%). Further and larger
      controlled studies are needed before the hypothesis can be definitely rejected.
      Despite our incomplete understanding about the relation between oral dryness and
      PN, professionals in oral health as well as in primary health have to strive for
      increased knowledge in this field.

PMID- 12810243
TI  - Autologous human keratinocytes cultured on membranes composed of benzyl ester of
      hyaluronic acid for grafting in nonhealing diabetic foot lesions: a pilot study.
AB  - Diabetic foot complications are the most common cause of nontraumatic lower
      extremity amputations in the industrialised world. Unsatisfactory healing
      requires advanced therapeutic strategies, such as the use of skin grafts, which
      may represent a helpful option for wound coverage. Alternatively, a method using
      autologous keratinocytes grown to thin sheet grafts is available. The purpose of
      this pilot study was to investigate the application of autologous human
      keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid
      (Laserskin autograft) to diabetic foot ulcers. We studied 14 patients with type 2
      diabetes mellitus and a nonhealing diabetic foot lesion, defined as existing
      longer than 6 months or with no wound healing apparent for 12 weeks. Between 7
      and 64 days after the transplantation (depending on the size of the ulceration),
      11/14 of the lesions were completely healed. The transplantation of autologous
      keratinocytes may allow faster closure of diabetic foot lesions and subsequently
      reduce length of hospitalization. This method can easily be planned with regard
      to logistics and time, and furthermore, this therapy option can be carried out by
      the diabetologist.

PMID- 12810244
TI  - Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy.
AB  - OBJECTIVE: To evaluate the vasodilation induced by topical application of methyl
      nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine
      (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic
      patients. RESEARCH DESIGN AND METHODS: Ten diabetic patients with peripheral
      neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were
      enrolled. The vasodilatory response to topical application of 1% MN and a placebo
      emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min
      was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to
      iontophoresis of 1% ACh and 1% SNP solutions was also evaluated. RESULTS: The
      maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and
      foot level in the diabetic patients. In the control group, the responses to MN,
      ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory
      response was higher when compared to the ACh and SNP responses. MN-related
      vasodilation was present 5 min after the application, reached its peak at 15-30
      min and declined to pre-application levels 120 min afterward. CONCLUSIONS:
      Topical application of MN at the forearm and foot levels of diabetic neuropathic
      patients results in skin vasodilation that is comparable to the maximal
      vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for
      less than 2 h. Further studies will be required to explore the potential of MN to
      increase blood flow and to prevent diabetic foot problems in clinical practice.

PMID- 12810245
TI  - Combination therapy with pioglitazone plus metformin or sulfonylurea in patients
      with Type 2 diabetes: influence of prior antidiabetic drug regimen.
AB  - PURPOSE: To evaluate two trials of combination therapy, pioglitazone together
      with metformin or sulfonylurea, for Type 2 diabetes mellitus and to examine how
      pretrial antidiabetic therapies may have influenced the results. SUBJECTS AND
      METHODS: The results of two published trials that examine combination therapy,
      pioglitazone plus metformin or pioglitazone plus sulfonylurea were analyzed. A
      post hoc analysis was performed in which patients from both of these trials were
      subdivided on the basis of their oral antidiabetic therapy before enrollment into
      the trials. Those subsets receiving pretrial therapy with a sulfonylurea plus
      metformin - and discontinuing one of the agents before randomization - were
      compared to those receiving only one of the agents before enrollment. RESULTS:
      Patients in the combination pioglitazone (30 mg/day) plus metformin therapy arm
      of one trial, who entered with stable metformin monotherapy, experienced a
      significant decrease in glycosylated hemoglobin (HbA(1C)) levels during the 16
      week course of the trial (-1.0+/-0.1 [mean+/-S.E.] percentage points; P<.05). In
      contrast, those in the same arm of the trial whose pretrial therapy included
      metformin plus a sulfonylurea - and who discontinued the sulfonylurea before
      enrollment - experienced no significant change in HbA(1C) levels (0.2+/-0.2
      percentage points; P>.05). The difference between groups was significant
      (P<.001). Patients in the combination pioglitazone (15 or 30 mg/day) plus
      sulfonylurea therapy arm of the other trial, who entered the trial on stable
      sulfonylurea monotherapy, experienced significant decreases in HbA(1C) levels (
      1.0+/-0.1 and -1.4+/-0.1 percentage points, respectively, for the 15- and 30-mg
      pioglitazone arms; P<.05). Those in the same arm whose pretrial therapy included
      sulfonylurea plus metformin - and who discontinued the metformin before
      enrollment - experienced no significant change in HbA(1C) levels. Differences
      between the groups separated on the basis of pretrial antidiabetic regimen were
      significant (P<.001). CONCLUSIONS: The efficacy of pioglitazone as an add-on in
      combination therapy (with metformin or a sulfonylurea) is likely to be greater
      than in previous reports, because those trial results were influenced by
      treatment regimens used by a portion of the patients before enrollment. Trials of
      oral hypoglycemic agents must be carefully constructed to consider the effects of
      agents given prior to the trial.

PMID- 12810246
TI  - The expanding scope of the metabolic syndrome and implications for the management
      of cardiovascular risk in type 2 diabetes with particular focus on the emerging
      role of the thiazolidinediones.
AB  - Over the last decade, new factors including endothelial dysfunction, vascular
      inflammation, and abnormalities of blood coagulation have joined more established
      components of the metabolic syndrome, such as hyperglycemia, hypertension,
      dyslipidemia, and visceral obesity. Many of these factors are known to promote
      atherosclerosis and the clustering of metabolic abnormalities within the syndrome
      makes a major contribution to the increased risk of cardiovascular disease and
      death associated with type 2 diabetes. Given that most patients have multiple
      cardiovascular risk factors, good glycemic control does not, by itself,
      adequately reduce the burden of cardiovascular disease associated with diabetes
      and clinical management needs to address the full profile of cardiovascular risk.
      The thiazolidinediones have potentially beneficial effects on many components of
      the metabolic syndrome and so may help to improve cardiovascular outcomes in type
      2 diabetes.

PMID- 12810247
TI  - Efficacy and reliability of fundus digital camera as a screening tool for
      diabetic retinopathy in Kuwait.
AB  - OBJECTIVE: Many screening and follow-up methods are available for detecting
      diabetic retinopathy (DR). However, once patients develop retinopathy, it is
      unclear as to what method should be used for their review. This study is designed
      to assess the correlation between fundus digital image and clinical examination
      and to develop a screening program for the early detection of sight-threatening
      DR using a Canon CF 60 UV fundus camera. METHODS: Patients who were not treated
      for DR earlier were enrolled in the study. All patients underwent digital fundus
      photography. The photographs were evaluated and compared with the clinical
      findings as recorded by retinal specialists. DR and macular edema were analyzed
      separately, and the correlation was statistically measured. The kappa statistic
      was used to estimate the extent of the agreement between the two procedures.
      RESULTS: A total of 92 eyes of 51 patients were eligible to be entered in the
      study. Comparison of the digital image of the fundus and the examination by an
      ophthalmologist showed a good correlation. The kappa score for retinopathy was
      estimated to be 93% with 95.6% concordance. The kappa score for diabetic
      maculopathy was 88% with concordance of 92.2%. CONCLUSION: We conclude that
      digital images provide an efficient method for diagnosing and classifying sight
      threatening DR, particularly proliferative diabetic retinopathy (PDR). However,
      agreement between the digital fundus camera and clinical examination by an
      ophthalmologist for diabetic maculopathy detection, though substantial
      statistically, was not very satisfactory. It was also felt that the digital
      photographs can be used as a tool for teleophthalmology and can be integrated as
      a screening system in Kuwait.

PMID- 12810248
TI  - Deletion of chromosome 15 represents a rare but recurrent chromosomal abnormality
      in myelocytic malignancies.
AB  - We report on three cases with myelocytic malignancies cytogenetically
      characterized by a deletion of chromosome 15 occurring as the sole cytogenetic
      aberration. The deletions were defined as del(15) (q12q21) (two cases) and
      del(15)(q11q21) (one case). Cytogenetic analysis was supplemented by fluorescence
      in situ hybridization (FISH) using a chromosome 15 specific whole chromosome
      painting probe and probes hybridizing to the UBE3A gene on 15q11~q13, the PML
      gene on 15q22, and the telomeric region of 15q. Hereby, an interstitial deletion
      of 15q including UBE3A, but not PML and the telomeric region of 15q could be
      demonstrated. Two of our patients were diagnosed as acute myelocytic leukemia
      (AML) with bone marrow dysplasia classified as AML-M6 and AML-M4, respectively,
      according to the French-American-British classification; the third patient
      suffered from a chronic myelomonocytic leukemia (CMMoL). In two cases, the
      aberration was found at the time of primary diagnosis, whereas the third case
      showed the del(15) only during relapse of leukemia. Both cases with acute
      leukemia did not adequately respond to intensive chemotherapeutic treatment and
      died 13 and 11 months, respectively, after primary diagnosis. Our findings and
      the data of five previously published cases with an isolated del(15) indicate
      that: 1) del(15) represents a rare but recurrent abnormality in myelocytic
      hemopathies; 2) in our cases, del(15) was interstitial and included the region
      15q11~q13/UBE3A, but not 15q22/PML and the telomeric region of 15q as shown by
      FISH; 3) del(15) occurs frequently in disorders with myelodysplastic or
      myeloproliferative features and may therefore affect early hematopoietic
      progenitor cells; and 4) del(15) may occur during disease progression and is
      often associated with an unfavorable prognosis.

PMID- 12810249
TI  - Loss of 1p and 7p in radiation-induced meningiomas identified by comparative
      genomic hybridization.
AB  - Cytogenetic and molecular studies of radiation-induced meningiomas (RIM) are rare
      and controversial. While comparative genomic hybridization (CGH) analysis
      identified monosomy 22 as the predominant change in RIM, occurring in frequencies
      comparable to those found in spontaneous meningioma (SM), molecular genetic
      analysis shows infrequent loss of chromosome 22 DNA markers. We have performed
      CGH analysis of six additional cases of RIM and detected an unbalanced genome in
      five of 6 cases. Loss of 1p and 7p was identified in the majority of RIM with an
      abnormal karyotype (4/5 cases), whereas loss of 6q occurred in three of five
      cases. Only one of five RIM had monosomy for chromosome 22. Loss of 7p is not
      frequently reported in SM and yet it was detected in four of 5 RIM with an
      abnormal karyotype in our study. Molecular and cytogenetic studies of chromosome
      7 copy number should be attempted on a larger number of RIM to further
      investigate the role of 7p loss in RIM.

PMID- 12810250
TI  - Chromosomal gains and losses in ocular melanoma detected by comparative genomic
      hybridization in an Australian population-based study.
AB  - To define the location of potential oncogenes and tumor suppressor genes in
      ocular melanoma we carried out comparative genomic hybridization (CGH) analysis
      on a population-based series of 25 formalin-fixed, paraffin-embedded primary
      tumors comprising 17 choroidal, 2 ciliary body, 4 iris, and 2 conjunctival
      melanomas. Twelve (48%) of the 25 melanomas showed no chromosomal changes and 13
      (52%) had at least one chromosomal gain or loss. The mean number of CGH changes
      in all tumors was 3.3, with similar mean numbers of chromosomal gains (1.5) and
      losses (1.8). The highest number of chromosomal changes (i.e., nine) occurred in
      a conjunctival melanoma and included four changes not observed in tumors at any
      other ocular site (gains in 22q and 11p and losses in 6p and 17p). The most
      frequent gains in all primary ocular melanomas were on chromosome arm 8q (69%),
      6p (31%) and 8p (23%) and the most frequent losses were on 6q (38%), 10q (23%),
      and 16q (23%). The most common pairing was gain in 8p and gain in 8q, implying a
      whole chromosome copy number increase; gains in 8p occurred only in conjunction
      with gains in 8q. The smallest regions of copy number alteration were mapped to
      gain of 8q21 and loss of 6q21, 10q21, and 16q22. Sublocalization of these
      chromosomal changes to single-band resolution should accelerate the
      identification of genes involved in the genesis of ocular melanoma.

PMID- 12810251
TI  - Cytogenetic characterization of three malignant peripheral nerve sheath tumors.
AB  - Malignant peripheral nerve sheath tumors (MPNST) are soft tissue sarcomas
      occurring frequently in patients with neurofibromatosis 1. We present three fully
      karyotyped cases of MPNST revealing aberrant near-triploid karyotypes. In all
      three cases we found deletions of chromosome arms or chromosomes 1p, 10q, 9, and
      15, as well as gain of chromosome 7 in two NF1-associated cases and gain of
      chromosome 8 in an NF1-associated and a sporadic case. The chromosomal region of
      the NF1 gene was cytogenetically unchanged in all cases, whereas two MPNST cases
      showed losses of the region 22q harboring the locus of the NF2 gene.

PMID- 12810252
TI  - Tetrasomy 6 and 6q14 deletion are associated with better survival in
      hepatocellular carcinomas. a fluorescence in situ hybridization study of 77
      cases.
AB  - We previously described frequent 6q14 deletion and polysomy 6 in 25
      hepatocellular carcinomas (HCC) by fluorescence in situ hybridization (FISH). A
      more favorable prognosis was noted in patients with 6q14 deletions. To confirm
      this clinical association, a two-colored FISH study was carried out on 77 HCC
      using a combination of a yeast artificial chromosome probe (813_E_12) of the 6q14
      region and a chromosome 6 centromeric probe (D6Z1) for simultaneous evaluation of
      the copy number change and chromosome arm deletion. The 77 HCC were divided into
      four groups according to the copy number of the centromeric signal: 26 with HCC
      (33.7%) were disomy for chromosome 6, 9 with HCC (11.7%) were trisomy, 29 with
      HCC (37.6%) were tetrasomy, and 13 with HCC (17%) were classified as hypersomy
      with presence of one major clone (>7%) of pentasomy or hexasomy of chromosome 6.
      Allelic loss at 6q14 was found in 40 with HCC (52%). The distribution of sex,
      age, stage, tumor size, tumor grade, and viral markers in each group showed no
      significant differences. An association with cirrhosis, however, was
      significantly lower in the hypersomy group (P = 0.001). The tetrasomy group had
      the best survival. An interaction between 6q14 deletion and numerical change of
      chromosome 6 on patients' survival were also noted. For patients with 6q14
      deletion, both disomy and tetrasomy groups had significantly better survival
      rates than trisomy and hypersomy groups. In contrast, no differences in survival
      rates could be observed among these four groups for patients without the 6q14
      deletion. The association with more favorable prognosis shown in this study
      indicates that tetrasomy 6 and 6q14 deletion may play an important role in the
      tumorigenesis of hepatocellular carcinoma and is worthy of further investigation.

PMID- 12810253
TI  - A xeno-transplantable plasma cell leukemia line with a split translocation of the
      IgH gene.
AB  - A novel cell line, SACHI, was established from a pericardial effusion developed
      during the course of primary plasma cell leukemia (PCL). The cell line SACHI
      cells were the same as the infiltrating plasma cells with regard to surface
      markers (CD38(+)CD19(-)PCA-1(+)VLA-5(-)CD56(-)TdT(+)) and immunoglobulin gene
      rearrangements. Analysis of SACHI cells showed a complex hypertriploid (karyotype
      mode 70-73) including 7p32, 14q32, and Xq24 structural abnormalities, which were
      found also in the original leukemia cells. Dual-color fluorescence in situ
      hybridization revealed that the c-MYC gene was juxtaposed with a constant region
      of IgG (Cgamma) on 14q32. The split Cgamma locus was fused near the MAFB gene on
      chromosome 20. The SACHI cells had increased amounts of c-MYC and MAFB
      transcripts. Injection of SACHI cells into NOD/SCID mice generated leukemic
      plasmacytosis with invasion to liver, spleen, and bone marrow. This cell line may
      be useful for therapeutic testing as well as analyzing the molecular pathogenesis
      of PCL.

PMID- 12810254
TI  - Cytogenetics, fluorescence in situ hybridization, and reverse transcriptase
      polymerase chain reaction are necessary to clarify the various mechanisms leading
      to an MLL-AF10 fusion in acute myelocytic leukemia with 10;11 rearrangement.
AB  - In acute myelocytic leukemia (AML), predominantly in AML M5a, a recurrent
      chromosome aberration involves 11q23/MLL and the short arm of chromosome 10.
      Molecular studies have shown that the AF10 gene at 10p12 is consistently a
      partner gene in cases with 10;11 rearrangement. A simple reciprocal translocation
      cannot lead to the known MLL-AF10 fusion transcript because the 3' part of the
      MLL gene is orientated to the telomere and the 3' part of the AF10 gene to the
      centromere. In a series of 1897 AML samples, 14 cases (0.74%) showed 10;11
      rearrangements leading to a MLL-AF10 fusion transcript. These cases were analyzed
      in detail with G banding analyses, fluorescence in situ hybridization, and
      molecular investigation in a single center. Five different mechanisms of (10;11)
      rearrangements leading to a MLL-AF10 fusion transcript can be observed (i.e.,
      reciprocal translocations, insertions of either 10p into 11q or 11q into 10p, as
      well as complex and cryptic rearrangements). Compared to translocations involving
      MLL and other partner genes, complex rearrangements are unique for MLL-AF10
      fusions. This may result from the opposite orientation of MLL and AF10.

PMID- 12810255
TI  - Establishment of a new human malignant fibrous histiocytoma cell line, FU-MFH-1:
      cytogenetic characterization by comparative genomic hybridization and
      fluorescence in situ hybridization.
AB  - Although a number of malignant fibrous histiocytoma (MFH) cell lines have been
      reported, their characterization at a molecular cytogenetic level has not been
      fully established. In this study, we established a new human cell line,
      designated as FU-MFH-1, from a storiform-pleomorphic MFH arising in the
      retroperitoneum of a 61-year-old woman, and applied comparative genomic
      hybridization (CGH) and fluorescence in situ hybridization (FISH) with chromosome
      painting probes for the characterization of chromosome alterations. FU-MFH-1
      cells were spindle, round, or polygonal in shape with oval nuclei, and were
      maintained continuously in vitro for over 50 passages for more than 12 months. G
      banding analysis was performed and FU-MFH-1 revealed a complex karyotype with an
      abnormal chromosome 19 containing a homogeneously staining region (hsr). CGH
      analysis showed a high-level amplification of 12q13-->q21. The high-level
      amplification detected by CGH was refined by FISH. These results showed that the
      hsr was composed of amplified DNA sequences from 12q. Our study emphasizes the
      usefulness of CGH as a powerful tool for chromosomal localization of amplified
      sequences. The FU-MFH-1 cell line should be useful for biologic and molecular
      pathogenetic investigations of human MFH.

PMID- 12810256
TI  - Arm-specific multicolor fluorescence in situ hybridization reveals widespread
      chromosomal instability in glioma cell lines.
AB  - An investigation of numerical and structural chromosome aberrations using
      chromosome arm-specific multicolor fluorescence in situ hybridization (armFISH)
      revealed considerable genetic heterogeneity among and within 11 glioma cell
      lines. Despite the substantial variation in numerical chromosome alterations
      among the cell lines, several distinct and glioma growth-associated losses or
      gains were frequently observed, that is, losses of chromosomes 10, 13, and 22 and
      gain of chromosome 7 in particular. Structural aberrations frequently affected
      chromosomes 1, 4, 7, 16, and 19; however, no single structural chromosome
      aberration common to all or even several glioma cell lines could be found.
      Structural alterations were often multiform, and a large variety of unstable
      chromosome structures were detected. Two of the cell lines also harbored small
      marker chromosomes containing mainly heterochromatin and chromosomal insertions
      within hetero-chromatic regions. Altogether, the armFISH provides a versatile
      tool for the identification of chromosomal aberrations as well as their formation
      patterns in tumors with a complex genome at the level of chromosome arms.

PMID- 12810257
TI  - Cytogenetic findings in a case of dedifferentiated chondrosarcoma.
AB  - Cytogenetic analysis of a case of dedifferentiated chondrosarcoma with a
      malignant fibrous histiocytoma (MFH) component revealed a near-triploid karyotype
      with multiple copies of chromosome 7, deletion of chromosome arm 9p, and a
      derivative chromosome 19 [add(19p)] in each metaphase. Whereas numerical
      anomalies of chromosome 7 have been frequently reported in chondrosarcoma,
      deletion 9p and add (19p) have been observed in MFH. A putative MFH tumor
      suppressor gene could be present in a critical region on chromosome bands
      9p21~p22.

PMID- 12810258
TI  - Monosomy 7p in meningiomas: a rare constituent of tumor progression.
AB  - We present karyotypes of 15 meningiomas with structural aberrations of chromosome
      7, which were taken from a consecutive series of 400 cytogenetically
      characterized meningiomas. Twelve of these tumors (80%) displayed partial or
      complete monosomy 7p with a consensus deleted region of 7p12 approximately pter,
      in 6 of 15 cases arising from an unbalanced whole-arm t(1;7)(q11;p11), and in 4
      of 15 cases from a whole-arm translocation involving other chromosomes. Other
      types of partial aneusomy 7 (3/15 cases) or balanced aberrations of chromosome 7
      (2/15 cases) were relatively rare. In most cases (11/15), the centromeric region
      of chromosome 7 was involved in the rearrangements. We conclude that in
      meningiomas, the near-centromeric region of chromosome 7 is particularly prone to
      structural rearrangements most frequently resulting in monosomy 7p. The
      investigation of the histopathologic features of this rare cytogenetic subgroup
      of meningiomas showed no clear genotype/phenotype correlation. As 7 of 11 of the
      meningiomas with monosomy 7p belonged to World Health Organization grades II or
      III, which usually comprise less than 20% of all meningiomas, partial loss of 7p
      appears to be involved in tumor progression in meningiomas. Because monosomy 7p
      is typically associated with the strongly progression-associated monosomy 1p,
      however, monosomy 7p represents a cofactor more than a stand-alone feature of
      meningioma progression.

PMID- 12810260
TI  - Application of comparative genomic hybridization technique for detection of
      chromosomal aberrations in benign cystic teratoma.
AB  - Benign cystic teratoma, also known as dermoid cyst, is the most common of all
      ovarian neoplasms accounting for 10%-20% of all ovarian cysts. Most have a normal
      46,XX karyotype. Less than 2% can undergo malignant transformation. By using the
      comparative genomic hybridization technique on nine benign ovarian cysts we were
      able to show two cases with chromosomal aberrations not seen before in dermoid
      cysts but known to be involved in malignant ovarian tumors. We speculate that
      these are the tumors carrying the potential for malignant transformation.

PMID- 12810259
TI  - Trisomy 13 in a patient with common acute lymphoblastic leukemia: description of
      a case and review of the literature.
AB  - Trisomy 13 occurring as a single cytogenetic abnormality has been associated with
      undifferentiated or biphenotypic acute leukemias and with an adverse prognostic
      outcome. We describe for the first time a case of B-cell common acute
      lymphoblastic leukemia (ALL) with trisomy 13 at diagnosis in an 18-year-old boy.
      The leukemic cells did not express myelocytic or T-cell associated antigens and
      no molecular abnormalities were detected. Following treatment, according to the
      GIMEMA ALL 0496 protocol, the patient achieved a brief (2 months) complete
      remission. At relapse, cytogenetic analysis showed karyotypic evolution that
      included two novel subclones carrying a del(6q), a del(7q), and an add(17q) in
      association with trisomy 13. In addition, immunophenotypic analysis revealed the
      coexpression of the CD33 and CD7 antigens on common ALL blasts, in accordance
      with other reported cases that displayed a predominant biphenotypic leukemia
      profile. The patient failed to obtain a second remission and died soon after due
      to infective complications. This report indicates that trisomy 13 can be found
      also in B-lineage ALL and underlines that this cytogenetic abnormality may
      identify a subgroup of male patients with clonal evolution potential and an
      adverse clinical outcome.

PMID- 12810261
TI  - An indolent B-cell lymphoma with t(2;8)(p12;q24) abnormality and absence of C-MYC
      amplification and TP53 deletion. A new variant?
AB  - The translocation between chromosomes 2 and 8, t(2;8), is well known for its
      strong association with high-grade Burkitt lymphoma. However, the significance of
      this translocation in indolent lymphoproliferative disorders is not clear. We
      present the case of a 75-year-old white male with left upper quadrant abdominal
      pain, splenomegaly, and an elevated white cell count of 30.3x10(9) cells/L (84%
      large lymphoid cells with scanty cytoplasm and prominent central nucleoli).
      Immunophenotyping revealed a clonal B-cell population coexpressing CD5, CD19, and
      CD20 with weak CD23 and CD25 and very weak, restricted, surface lambda. The
      cytogenetic analysis showed all 20 cells with t(2;8)(p12;q24.3). In addition,
      four of the 20 cells also showed a second translocation: t(12;17)(p13;q21).
      Molecular analysis using c-myc and p53 probes showed normal results with no
      indication of amplification of C-MYC or deletion of TP53. The patient was managed
      as an indo-lent/low-grade lymphoproliferative disorder with excellent response to
      eight cycles of fludarabine.

PMID- 12810262
TI  - Evaluation of PARVG located on 22q13 as a candidate tumor suppressor gene for
      colorectal and breast cancer.
AB  - Colorectal cancer (CRC) and breast cancer constitute common neoplasms in Western
      countries and leading causes of cancer-related death. Development and progression
      of both malignancies occur as a multistep process, requiring the activation of
      oncogenes and the inactivation of several tumor suppressor genes. Our group has
      recently identified a minimal region of deletion on 22q13 involved in CRC and
      breast cancer patients, which is highly indicative of the existence of a tumor
      suppressor gene (or genes). We performed mutation analysis of the PARVG gene, one
      of the genes present on the 22q13 region of interest, which has been previously
      demonstrated to have a reduced expression in some cancer cell lines. We have
      identified several DNA variants that are not compatible with pathogenic
      mutations. Accordingly, PARVG appears not to be a tumor suppressor gene involved
      in CRC and breast cancer development and progression.

PMID- 12810263
TI  - Interphase cytogenetic characterization of aberrations in the long arm of
      chromosome 1 in B-cell lymphoid malignancies.

PMID- 12810264
TI  - The common fragile site FRA16C does not map within the 16q smallest region of
      overlap number 2 frequently lost in breast carcinoma.

PMID- 12810265
TI  - Array comparative genomic hybridization analysis of myelodysplastic syndromes
      with complex karyotypes. A technical evaluation.

PMID- 12810266
TI  - Quorum sensing and expression of virulence in Escherichia coli O157:H7.
AB  - Enterohaemorrhagic Escherichia coli O157:H7 causes a characteristic
      histopathology in intestinal cells known as attaching and effacing lesion. The
      genes for the lesion are encoded by the Locus of Enterocyte Effacement (LEE)
      pathogenicity island, that encodes a type III secretion system, the intimin
      intestinal colonization factor, and the translocated intimin receptor protein
      that is translocated from the bacterium to the host epithelial cells. Expression
      of the operons encoded within LEE is complex, but recent studies have
      demonstrated that quorum sensing influences transcription from four of the LEE
      operon promoters. A transcriptional regulator (LuxR homologue), signal synthase
      (LuxI homologue), and autoinducer (acylhomoserine lactone) are indispensable for
      this system in most gram-negative bacteria. Vibrio harveyi, a gram-negative
      bioluminescent marine bacterium, regulates light production in response to two
      autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone produced by most gram
      negative bacteria. The structure of AI-2 is not known, but many species of gram
      positive and gram-negative bacteria, including E. coli and more specifically
      O157:H7, have been shown to produce AI-2 depending on the function encoded by the
      luxS gene. The LuxS acts as an AI-2 synthase and the AI-2 is produced from S
      adenosylmethionine in three enzymatic steps. The substrate for LuxS is S
      ribosylhomocysteine, which is cleaved to form two products, one of which is
      homocysteine, and the other is AI-2. The biosynthetic pathways and the
      biochemical intermediates in AI-2 biosynthesis have been observed to be identical
      in several gram-negative bacteria, such as E. coli, Salmonella typhimurium, V.
      harveyi, Vibrio cholerae, and Enterococcus faecalis. Thus, unlike quorum sensing
      via the family of related homoserine autoinducers, AI-2 is a universal signal,
      which may be used by a variety of bacteria for communication among and between
      species and may be responsible for regulation of virulence genes in E. coli
      O157:H7.

PMID- 12810267
TI  - Immunostimulatory oligonucleotide, CpG-like motif exists in Lactobacillus
      delbrueckii ssp. bulgaricus NIAI B6.
AB  - The present study was conducted to find an immunostimulatory oligonucleotide
      derived from yogurt starter cultures. The chromosomal DNA was purified from nine
      strains of Lactobacillus delbrueckii ssp. bulgaricus and six strains of
      Streptococcus thermophilus. An immunostimulatory ability of the DNA was examined
      in a proliferation of peyer's patch and splenic B cells. Only the DNA from L.
      bulgaricus NIAI B6 induced a significant proliferation of both cells. When the
      DNA was cloned and amplified using PCR, the mitogenic activities to B cells were
      significantly increased by 13 of 135 DNA clones. Ten homologous nucleotide
      sequences were found as possible oligonucleotide sequences of mitogens, and were
      then chemically synthesized (sOL-LB1 to sOL-LB10). One CpG-like motif (sOL-LB7;
      5'-CGGCACGCTCACGATTCTTG-3') was identified as an immunostimulatory
      oligonucleotide, but it did not contain palindromic CpG structure known as a B
      cell-specific mitogen. The sOL-LB7 substantially bound to B cells and increased
      the CD69 positive cells in peyer's patch cells. This study demonstrated that L.
      bulgaricus NIAI B6 was a good candidate of a starter culture for the production
      of new functional foods, "Bio-Defense Foods".

PMID- 12810268
TI  - Inhibition of Clostridium tyrobutyricum in Vidiago cheese by Lactococcus lactis
      ssp. lactis IPLA 729, a nisin Z producer.
AB  - Lactococcus lactis ssp. lactis IPLA 729 is a nisin Z producer isolated from raw
      milk cheese able to grow and produce nisin Z in milk. The ability of this strain
      to inhibit the growth of Clostridium tyrobutyricum CECT 4011, a late blowing
      agent, in Vidiago cheese, a semi-hard farmhouse variety, manufactured in
      Asturias, Northern Spain, was investigated. For control purposes, cheeses were
      manufactured with the mesophilic mixed starter IPLA-001. In experimental cheeses,
      the nisin-producing strain L. lactis IPLA 729 was combined with this starter.
      Nisin Z activity reached a concentration of 1600 AU/ml in 1-day cheeses and this
      level was maintained until 15 days of ripening. Furthermore, to compare the
      inhibitory activity of the nisin-producing strain to nitrate, cheeses were also
      manufactured with a commercial starter culture and potassium nitrate as anti
      blowing agent was added in accordance with Vidiago's cheesemakers. The control,
      experimental and commercial cheeses were contaminated with C. tyrobutyricum CECT
      4011. The composition of the three different cheeses showed only slight
      differences with respect to total solids, protein and fat, although control and
      experimental cheeses showed a richer flavour-compound profile than commercial
      cheeses. The level of the spoilage strain C. tyrobutyricum CECT 4011 decreased
      from 1.2x10(6) to 1.3x10(3) cfu/g during ripening in presence of the nisin Z
      producer, while it increased to 1.99x10(9) cfu/g in control cheeses and to
      3.5x10(7) cfu/g in commercial cheeses.

PMID- 12810269
TI  - Mode of action of lactocin 705, a two-component bacteriocin from Lactobacillus
      casei CRL705.
AB  - Lactocin 705 is a bacteriocin whose activity depends on the complementary action
      of two peptides (705alpha and 705beta) of 33-amino-acid residues each and is
      produced by Lactobacillus casei CRL705. Biologically active, synthetic lactocin
      705 was used to study the mode of action on sensitive cells of Lactobacillus
      plantarum CRL691. The addition of 90 nmol l(-1) of lactocin 705 to cells of L.
      plantarum dissipated both, the membrane potential (DeltaPsi) and the pH gradient
      (DeltapH). Energized membrane, obtained after the addition of glucose, were more
      susceptible to lactocin 705 action leading to the immediate release of
      intracellular K(+) and inorganic phosphate. When the role of various ions on
      sensitive cells were analyzed, only Ca(2+) ion exhibited a protective effect
      against lactocin 705. These data suggest that the presence of a proton motive
      force (PMF) promotes the interaction of the bacteriocin with the cytoplasmic
      membrane of energized cells, leading to pore formation which allows for the
      efflux of ions, thereby ensuring efficient killing of target bacteria.

PMID- 12810270
TI  - A RAPD-based comparison of thermophilic bacilli from milk powders.
AB  - The similarity of strains of thermophilic Geobacillus stearothermophilus
      (formerly Bacillus stearothermophilus), Anoxybacillus flavithermus (formerly
      Bacillus flavothermus), Bacillus licheniformis and Bacillus subtilis isolated
      from separate milk powder production runs from multiple factories was examined
      using a random amplified polymorphic DNA (RAPD) protocol. As a result of the
      analysis of the RAPD fingerprints and data relating to general growth and
      biochemical tests, over 98% of the 1470 isolates examined (grown at 55 degrees C)
      were assigned to the species G. stearothermophilus, A. flavithermus, B.
      licheniformis and B. subtilis. The G. stearothermophilus isolates were identified
      as being nearly identical to G. stearothermophilus (DSMZ 22; equivalent to ATCC
      12980), or G. stearothermophilus var. calidolactis (DSMZ 1550). Three groups of
      isolates were found to be related to A. flavithermus (DSMZ 2641) by partial small
      ribosomal subunit (16S) sequence comparisons and shown to be interrelated by RAPD
      analyses with multiple primer sets. The thermophilic isolates of B. licheniformis
      were positively identified by comparison with type strains of B. licheniformis
      DSMZ 13 and DSMZ 8785. All of the B. subtilis strains shared bands in their RAPD
      profiles and were similar to a common B. subtilis type strain (DSMZ 10 and DSMZ
      347). Overall, the most common and prevalent group of strains (group A) was
      demonstrated to be closely related to G. stearothermophilus (DSMZ 22).

PMID- 12810271
TI  - Application of a novel immunomagnetic separation-bacteriophage assay for the
      detection of Salmonella enteritidis and Escherichia coli O157:H7 in food.
AB  - Salmonella infection is the second most prevalent cause of foodborne illness in
      most developing countries. Meat, poultry, and dairy products are frequently
      implicated in outbreaks. The objective of this study was to apply a novel
      immunomagnetic separation (IMS)-bacteriophage assay to the detection of
      Salmonella enteritidis in artificially inoculated skimmed milk powder, chicken
      rinses, and ground beef. In all food types tested, the IMS-bacteriophage assay
      was able to detect an average of 3 CFU of S. enteritidis in 25 g or ml of food
      sample. Total assay time including pre-enrichment is about 20 h. The results
      indicate that the IMS-bacteriophage assay is a rapid and sensitive means of
      detecting S. enteritidis in these foods. The assay was successfully adapted to
      the detection of Escherichia coli O157:H7 and was able to detect E. coli in
      ground beef at the lowest inoculation level tested, 2 CFU/g. The assay was also
      adapted to the simultaneous detection of S. enteritidis and E. coli. The results
      indicate that the IMS-bacteriophage assay shows promise for the simultaneous
      detection of these pathogens, but further development work would be necessary to
      improve sensitivity and produce reliable results at low inoculation levels.

PMID- 12810272
TI  - Antibacterial activity of 11 essential oils against Bacillus cereus in
      tyndallized carrot broth.
AB  - The antibacterial activity of 11 essential oils from aromatic plants against the
      strain INRA L2104 of the foodborne pathogen Bacillus cereus grown in carrot broth
      at 16 degrees C was studied. The quantity needed by the essential oils of nutmeg,
      mint, clove, oregano, cinnamon, sassafras, sage, thyme or rosemary to produce 14
      1110% relative extension of the lag phase was determined. Total growth inhibition
      of bacterial spores was observed for some of the antimicrobial agents assayed.
      The addition of 5 microl cinnamon essential oil per 100 ml of broth in
      combination with refrigeration temperatures of <or=8 degrees C produced the
      conditions necessary to inhibit the growth of B. cereus for at least 60 days in a
      model, refrigerated minimally processed food product, made with carrots and
      tyndallized. This is especially important considering that the psychrotrophic
      enterotoxigenic strain of B. cereus INRA TZ415 was able to grow in this substrate
      at low temperatures in the absence of any essential oil. Furthermore, the study
      of the sensory characteristics of the final product suggests that the use of
      cinnamon essential oil can be considered as an alternative to "traditional food
      preservatives".

PMID- 12810273
TI  - Isolation of moulds capable of producing mycotoxins from blue mouldy Tulum
      cheeses produced in Turkey.
AB  - A total of 16 moulds was isolated and identified from 12 blue mouldy Tulum
      cheeses collected from retailers in Erzurum, Turkey; 12 were Penicillium
      roqueforti and 4 were Geotrichum candidum. The P. roqueforti isolates were grown
      in yeast sucrose broth at 5, 12 and 25 degrees C for 10 days, then extracted with
      chloroform and acetone and the extracts were examined for the presence of
      patulin, penicillic acid, roquefortine and PR toxin using thin layer
      chromatography. All of the P. roqueforti strains had toxin-producing ability at
      5, 12 and 25 degrees C, eight produced only at 5 and 12 degrees C and six could
      not produce toxin at 5 degrees C.

PMID- 12810274
TI  - Optimising growth conditions for the pectinolytic activity of Kluyveromyces
      wickerhamii by using response surface methodology.
AB  - This present study was undertaken to find optimum conditions of pH, temperature
      and, period of incubation for the pectinolytic activity of Kluyveromyces
      wickerhamii isolated from rotting fruits and to assess the effect of these
      factors by use of response surface methodology (RSM). A central composite
      rotatable design was used as an experimental design for the analysis of the
      allocation of treatment combinations. A second order polynomial regression model
      was fitted and was found adequate, with an R(2) of 0.94469 (P<0.001). The effects
      of temperature and pH were the most significant factors in influencing enzyme
      production. Estimated optimum conditions were as follows: pH 5.0, temperature, 32
      degrees C and an incubation period of 91 h. Pectinesterase (PE), pectin lyase
      (PL), and cellulase activities were not detected. Pectinase production was
      partially constitutive. Pectin was degraded by the isolated strain of K.
      wickerhamii in the current study, and the pectinolytic activity is referred to as
      polygalacturonase (PG) activity. Crude enzyme extract was thermostable at various
      temperatures and, stimulated by the presence of Ca(2+) ions but inhibited by
      other ions like Mg(2+), Zn(2+), Co(2+), Mn(2+) and Na(+).

PMID- 12810275
TI  - Detection of Salmonella spp., Yersinia enterocolitica and verocytotoxin-producing
      Escherichia coli O157 in pigs at slaughter in Italy.
AB  - From December 1999 to December 2000, 150 pigs were randomly selected in two large
      abattoirs of northern Italy. Caecal material and carcass swabs were collected and
      examined for Salmonella, Yersinia enterocolitica, and Escherichia coli O157.
      Tonsils were examined for Salmonella and Y. enterocolitica. Salmonella was
      isolated from the intestinal content of 55 (36.7%) specimens, from 8 (5.3%)
      tonsils, and from 9 (6.0%) carcasses. Ten different serotypes were detected; the
      more common were Salmonella derby (37.8%), Salmonella bredeney (21.6%), and
      Salmonella typhimurium (14.8%). S. typhimurium isolates that belonged to phage
      types DT104 and DT208 were 45% and 27.3%, respectively; 18.2% belonged to U302
      and 9.1% were non-typeable. Y. enterocolitica was detected in the intestinal
      matter of 6 (4.0%) slaughtered pigs and in 22 (14.7%) tonsils; however, this
      pathogen was not found on carcasses. The majority of Y. enterocolitica isolates
      (82.1%) belonged to serotype O:3 biotype 4, one (3.6%) belonged to serotype O:9,
      and 13% did not belong to any known biotype. Verocytotoxin-producing E. coli
      (VTEC) O157 was isolated from the intestinal content of one (0.7%) slaughtered
      pig and from one (0.7%) carcass; four (2.7%) faecal samples contained E. coli
      O157 strains negative for the presence of both eae and VT genes.

PMID- 12810276
TI  - Changes in selected biochemical and sensory parameters as affected by the
      superficial inoculation of Penicillium camemberti on dry fermented sausages.
AB  - An atoxigenic strain of Penicillium camemberti was superficially inoculated on
      fermented sausages in an attempt to improve their sensory properties. The growth
      of this mould on the surface of the sausages resulted in an intense proteolysis
      and lipolysis, which caused an increase in the concentration of free amino acids,
      free fatty acids (FFA) and volatile compounds. Many of these were derived from
      amino acid catabolism and were responsible for the "ripened flavour", i.e.
      branched aldehydes and the corresponding alcohols, acids and esters. The
      development of the fungal mycelia on the surface of the sausages also protected
      lipids from oxidation, resulting in both lower 2-thiobarbituric acid (TBARS)
      values and lipid oxidation-derived compounds, such as aliphatic aldehydes and
      alcohols. The sensory analysis of superficially inoculated sausages showed clear
      improvements in odour and flavour and, as a consequence, in the overall quality
      of the sausages. Therefore, this strain is proposed as a potential starter
      culture for dry fermented sausage production.

PMID- 12810277
TI  - Effects of fermentation temperature and Saccharomyces species on the cell fatty
      acid composition and presence of volatile compounds in wine.
AB  - Low temperature alcoholic fermentations are becoming more frequent due to the
      wish to produce wines with more pronounced aromatic profiles. However, their
      biggest drawback is the high risk of stuck and sluggish fermentations. Changes in
      the plasma membrane composition may be an adaptive response to low temperature
      fermentations. The production of volatile compounds and the changes in the
      membrane fatty acids were determined by GC to show the degree of cell adaptation
      and performance at low temperatures (13 degrees C) taking 25 degrees C as
      reference. The tests were done in two strains of Saccharomyces cerevisiae and one
      strain of Saccharomyces bayanus. Low temperatures restricted yeast growth and
      lengthened the fermentations. The analysis of plasma membrane fatty acids showed
      that dry yeasts had similar levels of unsaturation, between 70% and 80%, with no
      medium-chain fatty acids (MCFA). Long-chain saturated fatty acids (SFA) were the
      most frequent membrane fatty acids throughout the fermentations. Lipid
      composition changed with the growth temperature. The optimal membrane fluidity at
      low temperatures was modulated by changes in the unsaturation degree in S.
      cerevisiae strains. In S. bayanus, however, this change in the unsaturated fatty
      acid (UFA) percentage was not observed at different growth temperatures but the
      concentration of MCFA at low fermentation temperatures was higher. Concentrations
      of volatile compounds were higher in wines produced at lower temperatures and
      depended on the strain.

PMID- 12810278
TI  - Microbiology of wheat and flour milling in Australia.
AB  - A survey was undertaken to determine the microbiological status of Australian
      wheat and the distribution of microorganisms in the flour milling fractions and
      end products. A total of 650 milling process and end product samples was obtained
      from nine flour mills located in New South Wales (4), Queensland (2), Victoria
      (2) and Western Australia (1) during the 1997-1998 and 1998-1999 wheat seasons.
      Most frequent (modal) counts in wheat and flour were, respectively, as follows:
      aerobic mesophilic plate count, 10(5) and 10(2) colony forming units/gram
      (cfu/g); coliforms, 10 and 1 most probable number/gram (MPN/g); Bacillus spp.,
      10(4) and 10(2) cfu/g; B. cereus, 1 and 0.1 MPN/g; mesophilic aerobic spores, 10
      and 1 cfu/g; aerobic thermophiles, both 10 cfu/g; yeasts, 10(3) and 10(2) cfu/g,
      and moulds, 10(3) and 10(2) cfu/g. Bacillus spp., coliforms, yeasts and moulds
      were the most frequently detected microorganisms throughout the survey. The most
      common moulds isolated were Aspergillus, Penicillium, Cladosporium and Eurotium
      spp. Environmental serovars of Salmonella were isolated from two samples.
      Escherichia coli and B. cereus were present at very low levels, a majority of
      positive samples being at the minimum level of detection (3 and 0.3 MPN/g,
      respectively). As wheat grain layers are separated, surface-adhering contaminants
      are concentrated in end product bran, wheat germ and pollard, which comprise the
      outer layers of the grain. Consequently, the inner endosperm fraction contains
      lower microbial counts, and flour is the cleanest end product of the milling
      process. Higher microbiological counts midstream in the milling process indicate
      that equipment contamination may contribute to microbiological contamination;
      however, the microbiological quality of incoming wheat has a strong influence on
      the ultimate quality of milling end products.

PMID- 12810279
TI  - Damage of yeast cells induced by pulsed light irradiation.
AB  - DNA damage, such as formation of single strand breaks and pyrimidine dimers was
      induced in yeast cells after irradiation by pulsed light, which were essentially
      the same as observed with continuous ultraviolet (UV) light. The UV-induced DNA
      damage is slightly higher than seen with pulsed light. However, increased
      concentration of eluted protein and structural change in the irradiated yeast
      cells were observed only in the case of pulsed light. A difference in the
      inactivation effect between pulsed light and UV light was found and this
      suggested cell membrane damage induced by pulsed light irradiation. It is
      proposed that pulsed light can be used as an effective sterilizing method for the
      yeast Saccharomyces cerevisiae.

PMID- 12810280
TI  - Lactobacillus strains isolated from Danbo cheese as adjunct cultures in a cheese
      model system.
AB  - Isolates of Non-Starter Lactic Acid Bacteria (NSLAB) from six ripened Danbo
      cheeses of different ages and of different brands were examined. Special emphasis
      was on the genus Lactobacillus with the aim of investigating their role in cheese
      maturation. Thirty-three isolates were typed by the PCR-based method, Randomly
      Amplified Polymorphic DNA (RAPD). Ten RAPD types were found and 70% of the
      isolates were of RAPD types found in more than one cheese. The different RAPD
      types were identified to species level by Temporal Temperature Gradient Gel
      Electrophoresis (TTGE). Most of the isolates were identified as Lactobacillus
      paracasei (76%), but also Lactobacillus curvatus, Lactobacillus plantarum,
      Lactobacillus rhamnosus and some taxa originating from the starter culture were
      detected. In one cheese, no lactobacilli were found. One strain of the most
      frequent Lactobacillus RAPD type from each of the five cheeses with a
      Lactobacillus flora was used as adjunct cultures in a cheese model system. Four
      of the five adjuncts were re-isolated during ripening. Two adjunct containing
      model cheeses received higher flavour scores than the control while two other
      were associated with off-flavours. The two model cheeses with off-flavour had a
      similar microflora and both were after 13 weeks of ripening dominated by a strain
      identified as L. plantarum.

PMID- 12810281
TI  - The effect of temperature and pH on the growth of lactic acid bacteria: a pH
      auxostat study.
AB  - The growth of Streptococcus salivarius subsp. thermophilus, Lactococcus lactis
      subsp. lactis, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus
      acidophilus and Lactobacillus paracasei was studied in a pH-auxostat. The
      computer-controlled smooth change of pH or temperature was used to study the
      effect of pH and temperature on the culture characteristics (specific growth rate
      mu growth yield Y(ATP) and specific lactate production rate Q(ATP)). The
      behaviour of mu and Q(ATP) with an increase of temperature suggested that ATP
      production capacity was an important factor in determining the maximum growth
      rate of lactic acid bacteria (LAB). The decrease of Y(ATP) with increase of
      temperature resulted in the decrease of specific growth rate while Q(ATP)
      remained constant or even increased. With the decrease of pH, decrease of both
      Y(ATP) and Q(ATP) was observed. S. thermophilus St20 having the highest maximum
      specific growth rate of 2.2 h(-1) at 44 degrees C was the most acid sensitive
      strain. The L. paracasei E1H3 having the lowest mu(max) was the most tolerant
      strain to pH change. The behaviour of mixed culture of L. bulgaricus and S.
      thermophilus in milk in a pH-auxostat with pH-decrease was in agreement with the
      pure culture experiments of the same species. The study showed that pH-auxostat
      with smooth controlled change of pH and temperature is an effective method for
      determination of technological characteristics and comparative physiological
      study of LAB.

PMID- 12810282
TI  - Combinations of pulsed white light and UV-C or mild heat treatment to inactivate
      conidia of Botrytis cinerea and Monilia fructigena.
AB  - The use of pulses of intense white light to inactivate conidia of the fungi
      Botrytis cinerea and Monilia fructigena, responsible for important economical
      losses during postharvest storage and transport of strawberries and sweet
      cherries, was investigated in this study. In the first stage, a light treatment
      applying pulses of 30 micros at a frequency of 15 Hz was investigated, resulting
      in a treatment duration varying from 1 to 250 s. The conidia of both fungi showed
      similar behaviour to pulsed light, with a maximal inactivation of 3 and 4 log
      units for B. cinerea and M. fructigena, respectively. The inactivation of the
      conidia increased with increasing treatment intensity, but no complete
      inactivation was achieved. The sigmoidal inactivation pattern obtained by the
      pulsed light treatment was described using a modification of the model of
      Geeraerd et al. [Int. J. Food Microbiol. 59 (2000) 185]. Hereto, the shoulder
      length was incorporated explicitly and relative values for the microbial
      populations were used. In the second stage, combinations of light pulses and
      ultraviolet-C or heat were applied. The UV light used in the experiments is the
      short-wave band or UV-C, running from 180 to 280 nm with a peak at 254 nm (UV-B
      runs from 280 to 320 nm and UV-A from 320 to 380 nm). The UV-C doses were 0.025,
      0.05 and 0.10 J/cm(2), and the temperatures for the thermal treatment ranged from
      35 to 45 degrees C during 3-15 min. When combining UV-C and light pulses, there
      was an increase in inactivation for both B. cinerea and M. fructigena, and
      synergism was observed. There was no effect of the order of the treatments. For
      the heat-light pulses combination, there was a difference between both fungi. The
      order of the treatments was highly significant for B. cinerea, but not for M.
      fructigena. Combining heat and light treatments improved the inactivation, and
      synergism between both methods was again observed. Complete inactivation of M.
      fructigena conidia was obtained after, e.g., a 40-s pulsed light treatment and 15
      min at 41 degrees C, or after an 80-s light treatment and 10 min at 41 degrees C.

PMID- 12810283
TI  - Isolation of antimicrobial-resistant Escherichia coli from retail meats purchased
      in Greater Washington, DC, USA.
AB  - Four hundred and seventy-two generic Escherichia coli isolates were recovered
      from ground and whole retail beef, chicken, pork, and turkey obtained from
      Greater Washington, DC, USA during the years 1998 to 2000. Many of the isolates
      displayed resistance to tetracycline (59%), sulfamethoxazole (45%), streptomycin
      (44%), cephalothin (38%) and ampicillin (35%). Resistance was also observed, but
      to a lesser extent, to gentamicin (12%), nalidixic acid (8%), chloramphenicol
      (6%), ceftiofur (4%) and ceftriaxone (1%). Sixteen percent of the isolates
      displayed resistance to one antimicrobial, followed by 23% to two, 23% to three,
      12% to four, 7% to five, 3% to six, 2% to seven and 2% to eight. Three E. coli
      isolates were shown to possess Shiga toxin genes (stx2) via PCR; all were O non
      typeable and were recovered from ground beef samples purchased on the same day at
      the same supermarket. One of the Shiga toxin-producing E. coli (STEC) isolates
      was susceptible to each of the antimicrobials tested, whereas one displayed
      resistance to cephalothin and sulfamethoxazole, and one displayed resistance to
      ampicillin, cephalothin, gentamicin, streptomycin, sulfamethoxazole and
      tetracycline. Findings from this study indicate that retail raw meats may often
      be contaminated with antimicrobial-resistant E. coli.

PMID- 12810289
TI  - The effect of processed meat and meat starter cultures on gastrointestinal
      colonization and virulence of Listeria monocytogenes in mice.
AB  - Listeria monocytogenes is a foodborne pathogen of major concern to the food
      industry in general and the meat industry in particular. The aim of this study
      was firstly to identify a strain of Listeria that was virulent in SPF BALB/c
      mice. Secondly, to investigate if a traditional meat starter culture (FloraCarn)
      and nontraditional meat starter (NTMS) cultures of dairy product and human origin
      (Lactobacillus and bifidobacteria) inhibit this pathogen in vivo. In addition,
      the inhibition of Listeria was investigated in vitro. In vitro inhibition was
      investigated using an agar inhibition assay, where soft agar containing the
      pathogen was laid over colonies of NTMS cultures, and inhibition expressed as the
      zones of inhibition developing around the colonies. For assessment of virulence,
      mice were intragastrically challenged with broth cultures of five strains of
      Listeria. For assessment of anti-listeria effect in vivo, the Listeria strain
      proven to be most pathogenic (LM3) was given to mice in salami batter containing
      no other added cultures (control) or batter inoculated with either (1) FloraCarn,
      (2) a NTMS culture, or (3) a combination of FloraCarn and a NTMS culture. The
      batter was given to mice after a 3-day fermentation and faecal levels of pathogen
      and body weight were monitored. Intragastric challenge with LM3, but no other
      strains, resulted in a significant weight loss (p<0.05) and up to 10(6) colony
      forming units (cfu) of LM3 per gram faeces. No weight loss was observed in
      animals fed with salami batter containing LM3. Consumption of salami batter
      fermented by a combination of NTMS culture (Lactobacillus acidophilus LAFTI(R)
      L10) and FloraCarn reduced faecal levels of the pathogen by 2.5 log units
      compared to the control. Consumption of salami batter fermented with FloraCarn
      and LAFTI(R) L10 (L10) alone reduced faecal levels by 0.5-1 and 1.5 log units,
      respectively. Of the NTMS cultures investigated here, L10 displayed the greatest
      inhibition of LM3 in vitro. These results indicate that the ability of pathogenic
      Listeria to cause listeriosis is dependent on the nature of the food in which the
      pathogen is present, and that a traditional meat starter culture (FloraCarn) and
      some NTMS cultures, particularly L10, inhibit growth of the pathogen during
      passage through the gastrointestinal tract.

PMID- 12810290
TI  - Relevance of microbial interactions to predictive microbiology.
AB  - Microbial interaction can be ignored in predictive microbiology under most
      conditions. We show that interactions are only important at high population
      densities, using published data on inhibition of growth of Listeria monocytogenes
      in broth. Our analysis using growth models from predictive microbiology indicated
      that interactions only occur at population densities of approximately 10(8)
      cfu/ml of the protective cultures. Spoilage is evident at these levels, except
      for fermented foods. In bacterial colonies, diffusion limitation acts as a
      constraint to growth. We have shown that these constraints only become important
      after large outgrowth of colonies (in the order of 5-log growth in Lactobacillus
      curvatus colonies), which depends on the initial inoculation density. Intra
      colony interactions play an important role under these conditions. There is no
      large outgrowth of colonies when the initial inoculation densities are high and
      broth culture growth can be used to approximate colony growth.

PMID- 12810291
TI  - Relations between the occurrence of resistance to antimicrobial growth promoters
      among Enterococcus faecium isolated from broilers and broiler meat.
AB  - From 1995 to 2001, Enterococcus faecium isolates were collected from broiler
      flocks at slaughter and broiler meat products at retail outlets and were tested
      for susceptibility to classes of antimicrobials used for growth promotion in
      broilers in Denmark, namely: evernimicin, glycopeptide, macrolide and
      streptogramin. By February 1998, all antimicrobial growth promoters (AGPs) were
      withdrawn from the Danish broiler production. The present study investigates, by
      logistic regression analyses, the (1) changes in the occurrence of AGP resistance
      among E. faecium from broilers and broiler meat from the fourth quarter of 1995
      to the fourth quarter of 2001 and (2) relations between the occurrence of AGP
      resistance among E. faecium isolates from Danish broilers and AGP resistance
      among E. faecium isolates from the broiler meat of Danish and unknown origin
      collected in the same quarter within the year. In the present study, we showed
      that after the AGP withdrawal, a significant decline in resistance to avilamycin,
      erythromycin, vancomycin and virginiamycin was observed among E. faecium from
      broilers and broiler meat. In addition, a decline in the occurrence of AGP
      resistance among E. faecium from Danish broilers was associated with a decrease
      in the predicted probability of isolating an AGP-resistant E. faecium isolate
      from a randomly selected broiler meat product. In the analyses "relations between
      the occurrence of AGP resistance among E. faecium isolated from broilers and
      broiler meat collected in the same quarter" errors in the explanatory variable
      were expected. Therefore, a simulation study was performed to validate the
      results from logistic regression analyses. The results obtained by the two
      methods were similar.

PMID- 12810292
TI  - Genetic variability among isolates of Listeria monocytogenes from food products,
      clinical samples and processing environments, estimated by RAPD typing.
AB  - RAPD analysis with four primers was used to examine the genetic relationship
      among 432 strains of Listeria monocytogenes isolated from clinical and
      veterinarian cases of listeriosis, dairy, vegetable, meat- and fish-based food
      items, environmental samples and samples collected from one transport terminal,
      one poultry-processing company and four Atlantic salmon-processing plants. The
      purpose of the study was to determine whether clinical isolates belonged to a
      specific genetic group, whether links could be made between food groups and
      clinical cases and whether specific genetic groups were associated with specific
      food products or processing units. There was great genetic variability among the
      isolates, which produced a total of 141 RAPD composites based on the RAPD
      analysis with four primers. The RAPD composites divided in two major clusters and
      clinical isolates were evenly distributed in both of them. None of the isolates
      from food products had the same RAPD composite as isolates from human patients,
      thus, no particular food commodity could be linked to clinical cases. Each food
      processing environment was contaminated with more than one RAPD composite and the
      genetic variability found within each company was, in most cases, of
      approximately the same magnitude as the variability found when considering all
      the samples. In each plant, one or a few types persisted over time, indicating
      the presence of an established in-house flora. Our results indicate that most of
      the analysed cases of listeriosis were sporadic and, further, that these cases
      cannot be traced to a few specific food sources. We also found that no particular
      RAPD composite was better suited for survival in specific food types or food
      processing environments, indicating that although differences may be found in
      virulence properties of individual strains, all L. monocytogenes must be treated
      as potentially harmful.

PMID- 12810293
TI  - Screening for enterocins and detection of hemolysin and vancomycin resistance in
      enterococci of different origins.
AB  - The inhibitory activity of 122 out of 426 Enterococcus strains of geographically
      widespread origin and from different sources (food and feed, animal isolates,
      clinical and nonclinical human isolates) was tested against a wide range of
      indicator bacteria. Seventy-two strains, mainly belonging to the species
      Enterococcus faecium and Enterococcus faecalis were bacteriocinogenic. A
      remarkable variation of inhibitory spectra occurred among the strains tested,
      including inhibition of, for instance, only closely related enterococci, other
      lactic acid bacteria (LAB), food spoilage and pathogenic bacteria. No correlation
      could be found between the origin of the strains and the type of inhibitory
      spectrum, although a clustering of human isolates from both fecal and clinical
      origin was observed in the group of strains inhibiting lactic acid bacteria,
      Listeria, and either Staphylococcus or Clostridium. No relationship could be
      established between the presence of enterocin structural genes and the origin of
      the strain either, and hence no correlation seemed to exist between the presence
      of known enterocin genes and the activity spectra of these enterococci. The
      structural gene of enterocin A was widely distributed among E. faecium strains,
      whereas that of enterocin B only occurred in the presence of enterocin A. The
      vancomycin resistance phenotype as well as the presence of vancomycin resistance
      genes was also investigated. The vanA gene only occurred among E. faecium
      strains. The incidence of beta-hemolysis was not restricted to E. faecalis
      strains, but among the E. faecium strains the structural genes of cytolysin were
      not detected. beta-Hemolysis occurred in strains both from food and nonfood
      origin. It has been concluded that bacteriocin-producing E. faecium strains
      lacking hemolytic activity and not carrying cytolysin nor vancomycin resistance
      genes may be useful as starter cultures, cocultures, or probiotics.

PMID- 12810294
TI  - Effect of proteolytic starter cultures as leavening agents of pizza dough.
AB  - Lactic acid bacteria (LAB) and yeasts were selected on the basis of in vitro
      proteolytic activity against wheat gluten protein and then assayed as leavening
      agents for pizza dough. Trials were carried out to compare a proteolytic starter
      (Prt(+)), consisting of Lactobacillus sakei T56, Weissella paramesenteroides A51
      and Candida krusei G271, and a non-proteolytic starter (Prt(-)), consisting of
      Lb. sakei T58, W. paramesenteroides A58 and Saccharomyces cerevisiae T22. The
      proteolytic activity of the starter cultures was monitored immediately after
      mixing of the dough and throughout the fermentation process. The proteolytic
      activity was assessed by analysing the salt-soluble protein (SSP) and the dioxane
      soluble protein (DSP) fractions of the pizza dough by discontinuous SDS-PAGE.
      Only the Prt(+) starter exhibited considerable qualitative and quantitative
      changes in the electrophoretic patterns of the protein fractions extracted. After
      the fermentation, the Prt(+) and Prt(-) doughs were tested to evaluate the
      influence of the proteolytic activity on the mechanical properties of the dough
      before and after baking. Indications emerged suggesting an influence of the
      proteolytic activity on the viscoelasticity of pizza dough. The pizza dough with
      Prt(+) strains showed an increase in viscous properties during the fermentation
      as compared with the Prt(-) dough. Moreover, an increase in the firmness of the
      crumb was observed in Prt(+) baked pizza dough.

PMID- 12810295
TI  - Effect of Penicillium chrysogenum and Debaryomyces hansenii on the volatile
      compounds during controlled ripening of pork loins.
AB  - During ripening of meat products such as dry-cured ham, the moulds and yeasts
      that proliferate on the surface may contribute to flavour development. However,
      their contribution to volatile components of dry-cured meat products is not
      known. One strain each of Penicillium chrysogenum and Debaryomyces hansenii,
      selected from dry-cured ham by their proteolytic activity, were tested to
      determine their effect on the volatile compounds during ripening. Sterile pork
      loins were inoculated and ripened for 106 days. Volatile compounds collected with
      a Solid Phase Micro-Extraction (SPME) fibre were analysed by GC/MS. Inoculation
      of pork loins with P. chrysogenum lead to a decrease in compounds attributed to
      lipid oxidation and to an increase of compounds derived from free amino acids.
      Inoculation with D. hansenii seemed to favour the formation of complex alcohols.

PMID- 12810298
TI  - Expandable gastroretentive dosage forms.
AB  - Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3
      decades. They were originally created for possible veterinary use, but later the
      design was modified for enhanced drug therapy in humans. These GRDFs are easily
      swallowed and reach a significantly larger size in the stomach due to swelling or
      unfolding processes that prolong their gastric retention time (GRT). After drug
      release, their dimensions are minimized with subsequent evacuation from the
      stomach. Gastroretentivity is enhanced by the combination of substantial
      dimensions with high rigidity of the dosage form to withstand the peristalsis and
      mechanical contractility of the stomach. Positive results were obtained in
      preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow
      absorption window drugs compounded in such systems have improved in vivo
      absorption properties. These findings are an important step towards the
      implementation of expandable GRDFs in the clinical setting. The current review
      deals with expandable GRDFs reported in articles and patents, and describes the
      physiological basis of their design. Using the dog as a preclinical screening
      model prior to human studies, relevant imaging techniques and pharmacokinetic
      pharmacodynamic aspects of such delivery systems are also discussed.

PMID- 12810296
TI  - Contamination of bovine carcasses and abattoir environment by Escherichia coli
      O157:H7 in Istanbul.
AB  - The aim of this study was to investigate contamination of carcasses and abattoir
      environment with Escherichia coli O157:H7. Five abattoirs in Istanbul were
      visited between January 2000 and April 2001. During visits, sampling was
      performed and a total of 330 cattle were selected. Cattle were examined for the
      presence of faeces on the hide (abdomen and legs) before slaughter. The swabs
      from the carcasses and environmental samples (abattoir floor, benches including
      conveyors, knives, aprons, saws, hooks, hands) were taken at the abattoir
      immediately after slaughter using sterile cotton swabs. A sample from the wash
      water of the abattoir was also taken. Preenrichment, immunomagnetic separation
      and CT-SMAC agar were used for the isolation. The reaction of the isolates with
      anti-O157 and H7 antisera were also analysed. Twelve strains (3.6%) of E. coli
      O157 were isolated from the cattle carcasses and eight (2.4%) of them gave
      positive reaction with anti-H:7. Six strains of E. coli O157 were isolated from
      the environmental samples and all strains were positive for H7. The number of E.
      coli O157H:7 strains isolated from the environmental samples was two from the
      knife, two from the hands, one from the apron and one from the floor. No E. coli
      O157 was isolated from the abattoir water.

PMID- 12810299
TI  - Organosilicate-polymer drug delivery systems: controlled release and enhanced
      mechanical properties.
AB  - Dexamethasone-loaded poly(ethylene-co-vinyl acetate) (EVAc) nanocomposites were
      fabricated via solution-casting with three different organosilicates for study in
      a drug delivery system. X-ray diffraction (XRD) showed that all three
      nanocomposites were in an intercalated morphology. Release studies of
      dexamethasone into phosphate-buffered saline revealed that the presence of
      silicates reduced the rate of drug release, and this reduction was a function of
      volume fraction of silicate in the composite, as well as the aspect ratio of the
      silicate layers. It was also found that the presence of silicate in a
      nanocomposite resulted in an increase in the Young's modulus as compared to the
      pure polymer, and this increase was also a function of the volume fraction of
      silicate present as well as the aspect ratio of the silicate layers. Silicates
      are a viable additive to EVAc drug delivery systems, providing controlled release
      characteristics as well as enhanced mechanical properties in an economically and
      biologically safe manner.

PMID- 12810300
TI  - Effect of electric field on the enhanced skin permeation of drugs by
      electroporation.
AB  - Electroporation (voltage; 200 V) was applied using an exponentially decaying
      electric pulse generator on hairless rat skin using different shapes of
      electrodes, and the in vitro skin permeation of benzoate was measured as an index
      of the effectiveness of electroporation. Despite the same voltage of application,
      the skin permeation of benzoate was markedly different by the electrode shapes.
      Several experiments hereafter suggest that this reason was probably due to
      different 2-dimensional electric fields in the skin barrier, stratum corneum, and
      the voltage decreasing pattern applied. To confirm whether this phenomenon was
      specific for benzoate, diclofenac having a similar pKa was selected to carry out
      the same kind of examination. As a result, the skin permeability of diclofenac
      was influenced by 2-dimensional electric fields in the stratum corneum and the
      voltage decreasing pattern, similar to the benzoate permeation. Next, a
      rectangular pulse generator, where no decaying pattern was obtained for the
      application voltage, was used to measure the effect of electroporation on the
      skin permeation of diclofenac. As expected, the enhanced skin permeation of
      diclofenac was dependent only on the electric field when using the rectangular
      pulse generator. These results suggest that the electric field and time profile
      of the voltage (or AUC of voltage against time) at electroporation are very
      important factors to increase the efficacy of electroporation, and that the
      efficacy can be optimized by the shape of electrodes in addition to the
      application conditions of electroporation.

PMID- 12810301
TI  - Carbon dioxide extraction of residual solvents in poly(lactide-co-glycolide)
      microparticles.
AB  - A process for the reduction of residual solvents in spray-dried poly(lactide-co
      glycolide) (PLGA)-darbepoetin alfa microparticles was developed using carbon
      dioxide (CO(2)) as an extraction solvent. CO(2) was investigated in two phase
      states, liquid and gas. Detrimental effects on encapsulated protein integrity and
      microparticle morphology were observed with liquid CO(2) exposure. Extraction
      with CO(2) gas at <100 psig reduced residual solvent concentration and particle
      agglomeration was limited. Extraction rates and particle agglomeration increased
      with higher CO(2) gas pressures. The CO(2) pressures below which particles of
      polylactide (PLA) and PLGA microparticles significantly agglomerated were
      determined and the data used to develop extraction cycles. Extraction cycles were
      developed in which CO(2) gas pressure was increased as residual solvent
      concentration decreased in order to keep extraction rates high throughout the
      cycle. Spray dried darbepoetin alfa-PLGA microparticles were extracted with CO(2)
      gas and characterized for residual solvent concentration, process yield, particle
      size distribution, morphology, and protein integrity. The results indicated CO(2)
      gas may be used to reduce residual solvent to approximately 200 ppm with no
      significant detrimental effects on protein integrity or microparticle morphology.

PMID- 12810302
TI  - Pulmonary deposition of a budesonide/gamma-cyclodextrin complex in vitro.
AB  - Cyclodextrins (CDs) may be potential excipients in inhalation powders; e.g., to
      increase drug stability, dissolution rate and bioavailability, or to decrease
      local irritation of an inhaled drug. The aim of this study was to investigate the
      effect of CD complexation on the pulmonary deposition of drugs. Studies were
      performed by using novel Taifun multi-dose dry powder inhalers and budesonide as
      a model compound. A precipitation method was developed to prepare solid
      budesonide/gamma-CD complexes. Inhalation powders containing either
      budesonide/gamma-CD complexes (15 microg/dose; complex:carrier ratio 1:15) or
      budesonide (10 microg/dose and 100 microg/dose; drug:carrier ratio 1:159 and
      1:15, respectively) with a lactose carrier, were prepared by dry mixing. The in
      vitro pulmonary depositions of budesonide and budesonide/gamma-CD complexes were
      determined initially and after 1 month's storage (40 degrees C, 75% RH) using an
      Andersen cascade impactor. The respirable fraction (RF) of the budesonide/gamma
      CD complex was 35% initially and 31% after storage. The RF of budesonide was 35%
      (10 microg/dose) and 45% (100 microg/dose) initially, and 31% (10 microg/dose)
      and 51% (100 microg/dose) after storage, respectively. In conclusion, CDs may be
      used in inhalation powders to improve pharmaceutical and biopharmaceutical
      properties of drugs without lowering their pulmonary deposition.

PMID- 12810303
TI  - In vivo release and gene expression of plasmid DNA by hydrogels of gelatin with
      different cationization extents.
AB  - The objective of this paper is to investigate the in vivo release and gene
      expression of lacZ plasmid DNA (pSV-lacZ) by the hydrogels of cationized gelatin.
      Gelatin with different cationization extents was prepared by changing the amount
      of ethylenediamine added to aminize the carboxyl groups of gelatin with a water
      soluble carbodiimide. The cationized gelatin prepared was crosslinked by various
      concentrations of glutaraldehyde (GA) to obtain cationized gelatin hydrogels with
      different cationization extents as the release carrier of plasmid DNA. When the
      cationized gelatin hydrogels incorporating 125I-labeled pSV-lacZ were implanted
      into the femoral muscle of mice, the radioactivity remaining decreased with time
      and the retention period was prolonged with an increase in the concentration of
      GA used for hydrogel preparation. In vivo experiments with 125I-labeled
      cationized gelatin hydrogels revealed that the higher the GA concentration, the
      longer the in vivo retention period of radioactivity remaining for every
      cationized gelatin hydrogel. Only for the hydrogels prepared from gelatin with
      the aminized percentages of 29.7, 41.6, and 47.8 mol.%, the time profile of pSV
      lacZ retention correlated well with that of hydrogel retention. The gene
      expression by the cationized gelatin hydrogels incorporating pSV-lacZ depended on
      the aminized percentage of gelatin and was significant at the percentage of 41.6
      mol.% or higher. It is possible that the pSV-lacZ was complexed with the degraded
      fragments of cationized gelatin and released with a positive charge, resulting in
      enhanced gene expression. We conclude that gelatin with a cationization extent of
      at least 41.6 mol.% is needed for the enhanced in vivo gene expression of plasmid
      DNA by the hydrogel release system.

PMID- 12810304
TI  - Influence of silicone elastomer solubility and diffusivity on the in vitro
      release of drugs from intravaginal rings.
AB  - The in vitro release characteristics of eight low-molecular-weight drugs
      (clindamycin, 17beta-estradiol, 17beta-estradiol-3-acetate, 17beta-estradiol
      diacetate, metronidazole, norethisterone, norethisterone acetate and oxybutynin)
      from silicone matrix-type intravaginal rings of various drug loadings have been
      evaluated under sink conditions. Through modelling of the release data using the
      Higuchi equation, and determination of the silicone solubility of the drugs, the
      apparent silicone elastomer diffusion coefficients of the drugs have been
      calculated. Furthermore, in an attempt to develop a quantitative model for
      predicting release rates of new drug substances from these vaginal ring devices,
      it has been observed that linear relationships exist between the log of the
      silicone solubility of the drug (mg x ml(-1)) and the reciprocal of its melting
      point (K(-1)) (y=3.558x-9.620, R=0.77), and also between the log of the diffusion
      coefficient (cm(2) s(-1)) and the molecular weight of the drug molecule (g x mol(
      1)) (y=-0.0068x-4.0738, R=0.95). Given that the silicone solubility and silicone
      diffusion coefficient are the major parameters influencing the permeation of
      drugs through silicone elastomers, it is now possible to predict through use of
      the appropriate mathematical equations both matrix-type and reservoir-type
      intravaginal ring release rates simply from a knowledge of drug melting
      temperature and molecular weight.

PMID- 12810305
TI  - Gelled emulsion particles for the controlled release of lipophilic volatiles
      during eating.
AB  - Gelled emulsion particles are discussed in relation to controlling the release of
      lipophilic volatiles in the mouth during eating, using a mass spectroscopic
      technique that enables real time measurement of volatiles on the breath. Our
      studies have demonstrated that by encapsulating triglyceride oil droplets within
      biopolymer gelled particles (70-5000 microm), the initial flavour release maxima
      were reduced by kinetically inhibiting the mass transfer of flavour through the
      particle. An important feature of this approach was that it was the oil droplets
      and not the volatiles that were encapsulated. Factors such as particle size, oil
      phase volume and the partition coefficient of the volatile all affected the rate
      of volatile release. To control the temporal release profile, gelled emulsion
      particles have been designed that break down in a controlled manner under
      physiological conditions in the mouth. The physiological 'trigger mechanisms'
      investigated included mechanical failure, melting and enzyme hydrolysis.

PMID- 12810306
TI  - The in vivo transport of elastic vesicles into human skin: effects of occlusion,
      volume and duration of application.
AB  - In the present study, several aspects of elastic vesicle transport into human
      skin were investigated in vivo. Surfactant-based elastic vesicles were applied
      onto human skin in vivo and subsequently a series of tape-strippings were
      performed, which were visualised by freeze fracture electron microscopy. Factors
      of investigation for non-occlusive treatment were the duration of application and
      the volume of application. In addition, occlusive vs. non-occlusive application
      was studied. The results have shown a fast penetration of intact elastic vesicles
      into the stratum corneum after non-occlusive treatment, frequently via channel
      like regions. Intact vesicles could reach the ninth tape-strip after the 1-h non
      occlusive treatment. After the 4-h treatment, vesicle material could be found in
      the 15th tape-strip. However, micrographs of the 4-h treatment showed extensive
      vesicle fusion, both at the skin surface as well as in the deeper layers of the
      stratum corneum. A higher volume of application resulted in an increase in the
      presence of vesicle material found in the deeper layers of the stratum corneum.
      Micrographs after occlusive treatment revealed very few intact vesicles in the
      deeper layers of the stratum corneum, but the presence of lipid plaques was
      frequently observed. Furthermore, we have proposed a hypothesis that the channel
      like regions represent imperfections within the intercellular lipid lamellae in
      areas with highly undulating cornified envelopes.

PMID- 12810307
TI  - Short term dynamics of diatoms in an upland stream and implications for
      monitoring eutrophication.
AB  - A study designed to examine the effect of intermittent diffuse nutrient inputs on
      diatom assemblages in a small upland stream in northern England was confounded by
      other changes that occurred in the stream just before fertilisation started. A
      flora dominated by attached diatoms changed, over a period of about 3 weeks to
      one dominated by motile Nitzschia spp. In the absence of any likely human causes,
      the most likely reason for this change was undercutting of a meander upstream,
      releasing fine silts which favoured motile diatoms. Changes due to fertilisation
      by phosphorus were also recorded, with an increase in the proportion of Epithemia
      in samples, possibly favoured by the lower N:P ratio caused by the increased P
      concentration. The implication of these changes for monitoring eutrophication and
      ecological status in upland streams is discussed.

PMID- 12810308
TI  - Field intercomparison of throughfall measurements performed within the framework
      of the Pan European intensive monitoring program of EU/ICP Forest.
AB  - A 6-month field intercomparison study on throughfall measurements was performed
      at Speulder forest near the west coast in The Netherlands. Twenty throughfall
      sampling systems were evaluated on accuracy, sampling strategy and performance
      under field conditions. Throughfall fluxes of NO3-, K+ and Kjeldahl-N generally
      could be determined with a larger accuracy than fluxes of SO4(2-), NH4+, Na+, Cl
      , Mg2+, Ca2+, and alkalinity. Throughfall fluxes of H+ generally had the lowest
      accuracy. Only 20% of the sampling systems differed more than 20% from the best
      estimate, whereas 45% of the systems stayed within a 10% range from the best
      estimate. The difference from the best estimate was mainly caused by aspects
      related to sampling strategy, like, for example, collecting area, sampler
      placement. The inaccuracy induced by the sampling system appeared to be much
      larger than that resulting from the analysis of the samples by different
      laboratory as determined by ring-tests. The field intercomparison described in
      this article gave a good insight in the different aspects contributing to the
      overall accuracy of the measurements. However, performing a future field
      intercomparison is recommended for throughfall and stemflow in order to also take
      in account other aspects that might influence the performance of the different
      measurement systems (e.g. tree species, climate zone, summer/winter period).

PMID- 12810309
TI  - Field intercomparison of precipitation measurements performed within the
      framework of the Pan European Intensive Monitoring Program of EU/ICP Forest.
AB  - A 6-month field intercomparison study on precipitation measurements was performed
      at Schagerbrug near the west coast in the Netherlands. Twenty bulk sampling
      systems and two wet-only samplers were evaluated on accuracy, sampling strategy
      and performance under field conditions. Bulk precipitation fluxes of NO3-, NH4+,
      H+ and Kjeldahl-N generally could be determined with a greater accuracy than bulk
      precipitation fluxes of SO4(2-), Na+, Cl-, Mg2+, Ca2+, Alkalinity and H+. Bulk
      precipitation fluxes of K+ generally had the lowest accuracy. Only 20% of the
      sampling systems differed less than 10% from the best estimate, whereas most
      systems (60%) differed more than 20% from the best estimate. The inaccuracy
      induced by the sampling system appeared to be much larger than that resulting
      from the analysis of the samples by different laboratories as determined by ring
      tests.

PMID- 12810310
TI  - Accumulation features of persistent organochlorines in resident and migratory
      birds from Asia.
AB  - Concentrations of organochlorine contaminants including polychlorinated biphenyls
      (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs),
      hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs),
      hexachlorobenzene (HCB) were determined in the resident and migratory birds,
      which were collected from India, Japan, Philippines, Russia (Lake Baikal) and
      Vietnam. Accumulation patterns of organochlorine concentrations in resident birds
      suggested that the predominant contaminants of each country were as follows:
      Japan--PCBs Philippines--PCBs and CHLs, India--HCHs and DDTs, Vietnam--DDTs, and
      Lake Baikal--PCBs and DDTs. The migratory birds from Philippines and Vietnam
      retained mostly the highest concentrations of DDTs among the organochlorines
      analyzed, indicating the presence of stopover and breeding grounds of those birds
      in China and Russia. On the other hand, migratory birds from India and Lake
      Baikal showed different patterns of organochlorine residues, reflecting that each
      species has inherent migratory routes and thus has exposure to different
      contaminants. Species which have breeding grounds around the Red Sea and Persian
      Gulf showed high levels of PCBs, indicating the presence of areas heavily
      polluted by PCBs in the Middle East.

PMID- 12810311
TI  - Large-scale spatial variation in mercury concentrations in cattle in NW Spain.
AB  - Mercury (Hg) is a highly toxic environmental contaminant and man-made emissions
      account for between a quarter and a third of total atmospheric levels. Point
      discharges, particularly coal-burning power stations, are major sources of
      atmospheric Hg and can result in marked spatial variation in mercury deposition
      and subsequent uptake by biota. The aims of this study were to quantify the
      extent to which major point and diffuse sources of atmospheric Hg emissions
      affected accumulation of Hg by biota throughout Galicia and Asturias, two of the
      major regions in northwest Spain. We did this by relating renal Hg concentrations
      in locally reared cattle (n=284) to the proximity of animals to point and diffuse
      sources of Hg emissions. Mercury residues in calf kidneys ranged between non
      detected and 89.4 g/kg wet weight. Point discharges from coal-fired power plants
      in Galicia had the most dominant impact on Hg accumulation by calves in Galicia,
      affecting animals throughout the region and explaining some two-thirds of the
      variation in renal residues between animals located directly downwind from the
      plants. The effects of more diffuse emission sources on Hg accumulation in calves
      were not distinguishable in Galicia but were detected in cattle from neighbouring
      Asturias. The impact of both point and diffuse sources in elevating environmental
      levels of bioavailable Hg and subsequent accumulation by cattle extended to
      approximately 140-200 km downwind from source.

PMID- 12810312
TI  - Groundwater quality surrounding Lake Texoma during short-term drought conditions.
AB  - Water quality data from 55 monitoring wells during drought conditions surrounding
      Lake Texoma, located on the border of Oklahoma and Texas, was compared to assess
      the influence of drought on groundwater quality. During the drought month of
      October, water table levels were three feet (0.9 m) lower compared with several
      months earlier under predrought climate conditions. Detection frequencies of
      nitrate (> 0.1 mg/l), orthophosphates (> 0.1 mg/l), chlorides (> MCL), and
      sulfates (> MCL) all increased during drought. Orthophosphate level was higher
      during drought. Largest increases in concentration were nitrate under both
      agriculture lands and in septic tank areas. An increase in ammonium-nitrogen was
      only detected in the septic tank area. The study showed that stressors such as
      nitrate and total salts could potentially become a health or environmental
      problem during drought.

PMID- 12810313
TI  - Excess plutonium in soil near the Nevada Test Site, USA.
AB  - Two soil profiles were collected from undisturbed areas near the Nevada Test Site
      (NTS). The activity of 137Cs in the surface layer of the downwind Queen City
      Summit profile is three times higher than at the upwind site at Searchlight, NV
      (41.1+/-0.6 mBq/g vs. 13.0+/-0.4 mBq/g), and the 239,240Pu activity is 100 times
      greater (51+/-2 mBq/g vs. 0.52+/-0.03 mBq/g). An examination of the literature
      suggests that the 137Cs/239,240Pu and the 239,240Pu/238Pu activity ratios in
      soils and sediments from the northern hemisphere, due to fallout from atmospheric
      atomic weapons testing, have generalized values of 36+/-4 and 30+/-4,
      respectively (as of 1 July 1995). Deviations from these values may indicate
      possible contamination by sources other than fallout. Data from the surface soil
      of the downwind Queen City Summit profile yield a 137Cs/239,240Pu ratio of 0.81+/
      0.02 and a 239,240Pu/238Pu ratio of 78+/-6. Clearly, an increase in 239,240Pu
      relative to 137Cs or 238Pu can account for these observations. There is
      compelling evidence that this "excess" 239,240Pu came from activities at the NTS
      during the aboveground testing of nuclear devices, more than likely from safety
      tests, some 40 years ago, and/or during the interim by the wind-driven
      resuspension of contaminated surface soil on the NTS and its transport off-site.
      Moreover, the two concentration profiles show that high percentages of both of
      these elements are retained for decades in the upper few centimeters of soil in
      Nevada's desert environment.

PMID- 12810314
TI  - Scots pine (Pinus sylvestris L.) growth and condition in a polluted environment:
      from decline to recovery.
AB  - The results of long-term investigations of Scots pine (Pinus sylvestris L.)
      growth and condition in the impact zone of one of the biggest air pollution
      sources in Lithuania--mineral fertilizers plant "Achema" are presented. The main
      attention is laid to the recovery of damaged stands since annual emissions to air
      were reduced essentially. The investigations indicated, that the recovery of tree
      increment was mostly caused by distinct reduction of emissions of nitrogen and
      sulphur oxides and dust of mineral fertilizers. Despite reduced pollution, crown
      defoliation of investigated stands has continued to increase for a certain
      period. After the crown recovery of damaged stands has started, the recovery of
      most damaged survived trees was most intensive and convergence of defoliated to a
      different extend stands and trees is characteristic feature of this period. No
      defoliation threshold has been determined beyond of which recovery of trees would
      be impossible. Recovery of more than a quarter of damaged trees was registered
      even in the case of 90% of defoliation. Recovery of dominant trees occurs to be
      faster of that for suppressed trees within the same level of defoliation. The
      impact of stand density on the crown recovery rate is negative, the higher
      density (more intensive competition), the slower recovery of damaged trees. The
      dependence of growth rate on defoliation was found to be of logistic character:
      while crown defoliation consists up to 25-30%, tree increment losses are rather
      inconsiderable, further increase of defoliation leads to the essentially higher
      increment losses, however having achieved 65-70% defoliation, further increase of
      defoliation does not result such intensive decrease of radial increment.

PMID- 12810315
TI  - The solid-solution partitioning of heavy metals (Cu, Zn, Cd, Pb) in upland soils
      of England and Wales.
AB  - Ninety-eight surface soils were sampled from the uplands of England and Wales,
      and analysed for loss-on-ignition (LOI), and total and dissolved base cations,
      Al, Fe, and trace heavy metals (Cu, Zn, Cd, Pb). The samples covered wide ranges
      of pH (3.4-8.3) and LOI (9-98%). Soil metal contents measured by extraction with
      0.43 mol l-1 HNO3 and 0.1 mol l-1 EDTA were very similar, and generally lower
      than values obtained by extraction with a mixture of concentrated nitric and
      perchloric acids. Total heavy metal concentrations in soil solution depend
      positively upon soil metal content and [DOC], and negatively upon pH and LOI,
      values of r2 ranging from 0.39 (Cu) to 0.81 (Pb). Stronger correlations (r2=0.76
      0.95) were obtained by multiple regression analysis involving free metal ion
      (Cu2+, Zn2+, Cd2+, Pb2+) concentrations calculated with the equilibrium
      speciation model WHAM/Model VI. The free metal ion concentrations depend
      positively upon MHNO3 and negatively upon pH and LOI. The data were also analysed
      by using WHAM/Model VI to describe solid-solution interactions as well as
      solution speciation; this involved calibrating each soil sample by adjusting the
      content of "active" humic matter to match the observed soil pH. The calibrated
      model provided fair predictions of total heavy metal concentrations in soil
      solution, and predicted free metal ion concentrations were in reasonable
      agreement with the values obtained from solution-only speciation calculations.

PMID- 12810316
TI  - Specific accumulation of polychlorinated biphenyls and organochlorine pesticides
      in Japanese common squid as a bioindicator.
AB  - Organochlorines (OCs) representing Persistent Organic Pollutants (POPs) such as
      PCBs (polychlorinated biphenyls), DDTs (DDT and its metabolites), CHLs (chlordane
      compounds), HCHs (hexachlorocyclohexane isomers) and HCB (hexachlorobenzene) were
      determined in the liver of Japanese common squid (Todarodes pacificus) collected
      from the waters around Japan (Japan Sea and western North Pacific Ocean). Among
      OCs concentrations, PCBs (upto 5600 ng/g lipid wt.) were the highest, and those
      of other OCs were in the order of DDT> CHLs > HCHs > HCB. Studies on growth trend
      and seasonal variation of OCs in this species suggest a rapid reflection of the
      pollution levels in seawater where and when they were collected, regardless of
      body-length and time of collection. These results indicate that Japanese common
      squid is a suitable bioindicator for monitoring OCs pollution in waters around
      Japan. With regard to the geographical distribution of OCs in this species
      collected from waters around Japan, OCs concentrations in specimens from Japan
      Sea were higher than those from the Pacific Ocean. This result might reflect some
      existing of local pollution sources of OCs around Japan Sea, and slower water
      exchange between Japan Sea and open ocean.

PMID- 12810317
TI  - Ameliorating effects of industrial sugar residue on the Jales gold mine spoil (NE
      Portugal) using Holcus lanatus and Phaseolus vulgaris as indicators.
AB  - Phytostabilisation of bare heavily contaminated substrate, such as abandoned mine
      sites, is considered a very appropriate technology in order to diminish erosion
      and dispersion of contaminants into the surroundings. In this short-term pot
      study, application of industrial sugar residue (ISR), a waste product of the
      sugar industry, proved to ameliorate spoils conditions for plant performance by
      elevating pH and immobilising several metals. Although arsenate concentrations
      were positively correlated to spoil pH and spoil treatment with ISR mobilised As,
      growth of both Phaseolus vulgaris and Holcus lanatus improved significantly after
      applications of 3.75 g ISR kg(-1) dry spoil. Nutrient uptake from the substrate,
      with the exception of potassium, was elevated by ISR. As a remediation technique
      ISR application could be effective although in As-contaminated sites application
      might be restricted to areas where leaching to (ground) water does not form a
      risk.

PMID- 12810318
TI  - Rapid oxidation of sulfide mine tailings by reaction with potassium ferrate.
AB  - The chemistry of sulfide mine tailings treated with potassium ferrate (K2FeO4) in
      aqueous slurry has been investigated. The reaction system is believed to parallel
      a geochemical oxidation in which ferrate ion replaces oxygen. This chemical
      system utilized in a pipeline (as a plug flow reactor) may have application
      eliminating the potential for tailings to leach acid while recovering the metal
      from the tailings. Elemental analyses were performed using an ICP spectrometer
      for the aqueous phase extract of the treated tailings; and an SEM-EDX for the
      tailing solids. Solids were analyzed before and after treatments were applied.
      ICP shows that as the mass ratio of ferrate ion to tailings increases, the
      concentration of metals in the extract solution increases; while EDX indicates a
      corresponding decrease in sulfur content of the tailing solids. The extraction of
      metal and reduction in sulfide content is significant. The kinetic timeframe is
      on the order of minutes.

PMID- 12810319
TI  - Fish mercury levels in lakes--adjusting for Hg and fish-size covariation.
AB  - Accurate estimates of lake-specific mercury levels are vital in assessing the
      environmental impact on the mercury content in fish. The intercepts of lake
      specific regressions of Hg concentration in fish vs. fish length provide accurate
      estimates when there is a prominent Hg and fish-size covariation. Commonly used
      regression methods, such as analysis of covariance (ANCOVA) and various
      standardization techniques are less suitable, since they do not completely remove
      the fish-size covariation when regression slopes are not parallel. Partial least
      squares (PLS) regression analysis reveals that catchment area and water chemistry
      have the strongest influence on the Hg level in fish in circumneutral lakes. PLS
      is a multivariate projection method that allows biased linear regression analysis
      of multicollinear data. The method is applicable to statistical and visual
      exploration of large data sets, even if there are more variables than
      observations. Environmental descriptors have no significant impact on the slopes
      of linear regressions of the Hg concentration in perch (Perca fluviatilis L.) vs.
      fish length, suggesting that the slopes mainly reflect ontogenetic dietary shifts
      during the perch life span.

PMID- 12810320
TI  - Effects of salinity, pH and temperature on the re-establishment of
      bioluminescence and copper or SDS toxicity in the marine dinoflagellate
      Pyrocystis lunula using bioluminescence as an endpoint.
AB  - Pyrocystis lunula is a unicellular, marine, photoautotrophic, bioluminescent
      dinoflagellate. This organism is used in the Lumitox bioassay with inhibition of
      bioluminescence re-establishment as the endpoint. Experiments determined if acute
      changes in pH, salinity, or temperature had an effect on the organisms' ability
      to re-establish bioluminescence, or on the bioassay's potential to detect sodium
      dodecyl sulfate (SDS) and copper toxicity. The re-establishment of
      bioluminescence itself was not very sensitive to changes in pH within the pH 6-10
      range, though reducing pH from 8 to levels below 6 decreased this capacity.
      Increasing the pH had little effect on Cu or SDS toxicity, but decreasing the pH
      below 7 virtually eliminated the toxicity of either compound in the bioassay.
      Lowering the salinity from 33 to 27 per thousandth or less resulted in a
      substantial decrease in re-establishment of bioluminescence, while increasing the
      salinity to 43 or 48 per thousandth resulted in a small decline. Salinity had
      little influence on the bioassay's quantification of Cu toxicity, while the data
      showed a weak negative relationship between SDS toxicity and salinity. Re
      establishment of bioluminescence showed a direct dependence on temperature, but
      only at 10 degrees C did temperature have an obvious effect on the toxicity of Cu
      in this bioassay.

PMID- 12810321
TI  - Lichens as biomonitors of uranium in the Balkan area.
AB  - The contribution of the conflict of 1999 to the environmental levels of uranium
      in the Balkan area was evaluated by means of lichens used as biomonitors. The
      average U concentration found in lichens in the present study was in line with
      the values reported for lichens from other countries and well below the levels
      found in lichens collected in areas with natural or anthropogenic sources of U.
      Measurement of isotopic ratios 235U/238U allowed to exclude the presence of
      depleted uranium. According to these results, we could not detect widespread
      environmental contamination by depleted uranium in the Balkan area.

PMID- 12810322
TI  - Mercury in fish from three rift valley lakes (Turkana, Naivasha and Baringo),
      Kenya, East Africa.
AB  - Total mercury (THg) concentrations were measured for various fish species from
      Lakes Turkana, Naivasha and Baringo in the rift valley of Kenya. The highest THg
      concentration (636 ng g(-1) wet weight) was measured for a piscivorous tigerfish
      Hydrocynus forskahlii from Lake Turkana. THg concentrations for the Perciformes
      species, the Nile perch Lates niloticus from Lake Turkana and the largemouth bass
      Micropterus salmoides from Lake Naivasha ranged between 4 and 95 ng g(-1). The
      tilapiine species in all lakes, including the Nile tilapia Oreochromis niloticus,
      had consistently low THg concentrations ranging between 2 and 25 ng g(-1). In
      Lake Naivasha, the crayfish species, Procambrus clarkii, had THg concentrations
      similar to those for the tilapiine species from the same lake, which is
      consistent with their shared detritivore diet. THg concentrations in all fish
      species were usually consistent with their known trophic position, with highest
      concentrations in piscivores and declining in omnivores, insectivores and
      detritivores. One exception is the detritivore Labeo cylindricus from Lake
      Baringo, which had surprisingly elevated THg concentrations (mean=75 ng g(-1)),
      which was similar to those for the top trophic species (Clarias and Protopterus)
      in the same lake. Except for two Hydrocynus forskahlii individuals from Lake
      Turkana, which had THg concentrations near or above the international marketing
      limit of 500 ng g(-1), THg concentrations in the fish were generally below those
      of World Health Organization's recommended limit of 200 ng g(-1) for at-risk
      groups.

PMID- 12810323
TI  - Two new growth inhibition tests with the filamentous algae Ceramium strictum and
      C. tenuicorne (Rhodophyta).
AB  - Two growth inhibition tests using the red marine macroalgae Ceramium strictum and
      the brackish water relative C. tenuicorne have been developed. Besides using
      phenol as a reference substance, the toxicity of a metal, a flame retardant and a
      complex effluent water were assayed. The two methods are reliable and repeatable
      bioassays for salinities between 4 and 30 per thousandth. The coefficients of
      variation (CV) for toxicity of the reference substance phenol were 15% for the
      Stereo Microscope Analysis test and between 24 and 51% for the Computer Image
      Analysis test (n=5). Ceramium spp. are common and important primary producers in
      temperate coastal waters and are thus relevant as test organisms. Both algae grow
      well in laboratorial conditions and tests can be performed all year around.

PMID- 12810324
TI  - Effects of fenoxycarb exposure on complete larval development of the xanthid
      crab, Rhithropanopeus harrisii.
AB  - Pest control agents, such as juvenile hormone analogues (JHA), have been
      developed to limit effects on non-target organisms that co-inhabit insect pest
      habitats. Rhithropanopeus harrisii, an estuarine xanthid crab, was used to
      observe the impacts of the JHA, fenoxycarb, on the pattern of complete larval
      development as well as survival of larvae and successful metamorphosis to first
      crab stage. Significant mortality occurred in the first of four zoeal stages
      (after 2-3 days of exposure) at the highest treatment of 240 microg fenoxycarb/l
      and in megalopae exposed to 48 microg fenoxycarb/l. The time required to
      metamorphose to the first crab stage was significantly increased for megalopae in
      all treatments 48 microg/l. This delay in development was sufficient to
      significantly prolong the entire developmental period from zoea to crabs.
      Unexposed larvae developed to crabs in an average of 16 days; larvae exposed to
      >/=48 microg/l required 19-20 days. Reduced survival and extended duration of
      developing larval stages in the life history of a benthic invertebrate may alter
      the population dynamics of these organisms in the estuary.

PMID- 12810325
TI  - Urban disadvantage and delayed nephrology referral in Australia.
AB  - This paper explores the relationship between area level measures of social
      disadvantage and the late referral of patients with end-stage renal disease
      (ESRD) to a nephrologist. Patients who were referred late were those who needed
      to commence dialysis within 3 months of referral to a nephrologist. Late referral
      has been associated with increased morbidity and mortality. We studied 3334
      patients who started ESRD treatment in Australian capital cities between 1 April
      1995 and 31 December 1998. The proportion referred late varied between areas, was
      higher in areas of greater disadvantage and was significantly related to the age-
      and sex-standardised incidence of ESRD. This may indicate inequitable access to
      optimal pre-ESRD care.

PMID- 12810326
TI  - Height of young men.
AB  - We analysed the height of young men in Belgium, using 613 257 records of medical
      examinations made prior to their conscription into the army (about 68% of the
      male population concerned). All analyses showed very significant associations.
      Height differed according to the region (-1.24cm in Wallonia, French-speaking and
      poorer) compared to Flanders (Dutch-speaking and richer), when "age-class" and
      year are taken into account. The smallest men lived in Hainaut (a deprived area),
      the tallest ones in Walloon Brabant (wealthy green suburbs of the capital).
      Height increased across time (+1.11cm, 1978-1990) and with "age-class" (+2.66cm,
      18-26years), controlling for other factors. The increase in Brussels stops in
      1983, probably due to other socio-demographic evolutions.

PMID- 12810327
TI  - Self-assessed health--a case study of social differentials in Soweto, South
      Africa.
AB  - The study of the relationship between health and social differentials as a focus
      of research is not new. However, most of the studies originate in the Western
      developed world and are thus informed by this specific social and cultural
      context. The aim of the paper was to analyse the relationship between health and
      a range of social factors in a specific social context of a relatively deprived
      community in South Africa. It is based on a secondary analysis of data collected
      in a comprehensive social survey of Soweto conducted in 1997. A total of 2947
      interviews were used for the current analysis. An attempt was made to explore
      basic measures of social inequality as well as more sophisticated indicators of
      social relationships and access to "social resources" and how they are linked to
      people's perception of their own health. The results reveal a clear relationship
      between health and a range of socio-economic indicators of inequalities. Health
      is significantly associated with a good "perception about the living environment"
      and "access to social resources". This paper presents an interesting scenario
      which -while reaffirming the already established connection between social
      differentials and health-also sheds light on a different social context and
      specific relationships with regard to health. It also points towards the ways
      people try to cope with the psycho-social stressor emanating from their specific
      context.

PMID- 12810328
TI  - What features of the home and the area might help to explain observed
      relationships between housing tenure and health? Evidence from the west of
      Scotland.
AB  - This study aimed to explore the role of dwelling conditions and neighbourhood
      characteristics in explaining the frequently observed association between housing
      tenure and health. A postal questionnaire, focusing on a number of specific
      aspects of the home and the area, was sent to a random sample of adults in the
      west of Scotland (achieved sample size 2867, response rate 50%). The health
      measures were limiting long-standing illness, self-assessed health, recent
      symptoms, and anxiety and depression. Having controlled for age, sex, and marital
      status, housing tenure explained, respectively, 2.7%, 5.4%, 3.9%, 2.4% and 5.4%
      of the variance in these variables. These percentages were reduced by between 93%
      (for anxiety) and 73% (for self-assessed health) when housing problems, housing
      fixtures, overcrowding, dwelling type, access to garden, area type and area
      amenities were introduced into the model. This suggests that features of the
      dwelling and its surroundings help to explain observed associations between
      tenure and health in the UK, and that housing and area problems may be
      particularly important. Housing improvements and urban regeneration may help to
      reduce the health gap between housing tenures, and more generally to reduce
      inequalities in health.

PMID- 12810329
TI  - 'Everywhere and nowhere': locating and understanding the 'new' public health.
AB  - Public health was recently described as being 'everywhere and nowhere' (Br.
      Med.J. 319(7213)(1999)839). This image captures the idea that public health is
      shaped by a range of social, environmental and physiological influences, and that
      these are mapped across the activities and practices of a range of players. It
      also suggests it is difficult to capture the spaces of public health. This paper
      explores how theoretical and methodological developments in the social sciences,
      in particular ideas around reflexive modernisation, can help us to read the
      complex terrain of public health policy and practice, and visualise these spaces
      more clearly.

PMID- 12810330
TI  - City-level gender differentials in the prevalence of dental caries and
      restorative dental treatment.
AB  - This study assesses gender differentials in the distribution of dental caries and
      restorative treatment at the city level in order to discuss gender inequities in
      health. We retrieved data for caries prevalence and dental service utilisation by
      11- and 12-year-old girls and boys in 131 towns in the state of Sao Paulo,
      Brazil, 1998. We also gathered aggregate population data for these towns, and
      information already held by the health authority regarding the provision of
      dental services. Results of data analysis indicated that girls presented higher
      caries indices in permanent teeth than boys of the same age, concurrent with a
      higher utilisation of dental care. When studying aggregate data at the city
      level, we gathered evidence reinforcing the hypothesis that the higher prevalence
      of caries in girls is attributable to their earlier eruption of permanent teeth,
      with no significant association between this excess and indices of socio-economic
      status at the city level. However, indices assessing the discrepant incorporation
      of dental services between genders were higher in towns with a poorer profile of
      socio-economic status. We also observed that towns whose public health service
      was more effective in providing dental care presented a more equitable gender
      distribution of dental services. Public resources destined to dental assistance
      contributed to reducing inequities in oral health by allowing an incorporation of
      restorative dental treatment more equitably distributed between girls and boys.

PMID- 12810331
TI  - Visual localisation of community health needs to rational decision-making in
      public health services.
AB  - The objectives were to visualise the locations of community health needs and to
      develop a community health needs assessment geographic information system (GIS)
      for rational decision-making in public health services. We compiled census data,
      digital data of basic planning maps, digital data of topographic maps, contents
      of registers of medical and welfare facilities, and statistics of establishments
      into a geographical database; visualised geographical distributions of specific
      community health needs by integrating sets of indicators to reflect individual
      needs; and quantified their clustering by the nearest neighbour method. The
      database aggregated 3400 items of demographic, life and environmental factors.
      Thematic maps and clustering values showed different patterns of geographical
      distribution of the individual community needs. Means to match needs with
      services in smaller geographical units were discussed. This GIS will support
      appropriate resource allocation, intersectoral collaboration and greater
      transparency in planning and implementing services, by visualising locations of
      community health needs.

PMID- 12810332
TI  - One-stop health centres: what co-location means for pharmacy.
AB  - This paper examines the potential for the development of patient services that
      could arise from the co-location of pharmacies with medical practices in the new
      "one-stop" centres. A review of the pharmacy-specific literature shows limited
      understanding of influence of location upon service development and highlights a
      tension between the professional and commercial drives. The aim of the survey of
      health centre pharmacists was to describe the current patterns of integration in
      the primary health care team. The study demonstrates that co-location offers
      opportunities but that there are barriers linked to the loss of traditional
      commercial activity.

PMID- 12810333
TI  - Neighborhood poverty and self-reported health among low-income, rural women, 50
      years and older.
AB  - We examined the relationship between neighborhood socioeconomic context and self
      reported health among low-income, rural women aged 50+ years, without a history
      of breast cancer. Tract-level census data were linked to individual level data
      from the baseline survey of a community trial to increase breast cancer screening
      rates. Generalized estimating equations were used to analyze data for 1988 women
      and 56 census tracts. Neighborhood poverty was associated with a greater
      likelihood of poor self-reported health, adjusted for age, race and socioeconomic
      status (OR=1.35, 95% CI=1.08-1.68). This effect was greatest for individuals with
      incomes below the median neighborhood income.

PMID- 12810334
TI  - Visualization of the spatial scan statistic using nested circles.
AB  - We propose a technique for the display of results of Kulldorff's spatial scan
      statistic and related cluster detection methods that provides a greater degree of
      informational content. By simultaneously considering likelihood ratio and
      relative risk, it is possible to identify focused sub-clusters of higher (or
      lower) relative risk among broader regional excesses or deficits. The result is a
      map with a nested or contoured appearance. Here the technique is applied to
      prostate cancer mortality data in counties within the contiguous United States
      during the period 1970-1994. The resulting map shows both broad and localized
      patterns of excess and deficit, which complements a choropleth map of the same
      data.

PMID- 12810336
TI  - Cost-utility analysis of vagus nerve stimulators for adults with medically
      refractory epilepsy.
AB  - INTRODUCTION: The cost-utility of vagus nerve stimulator (VNS) devices for
      medically refractory epilepsy has yet to be estimated. METHODS: Using a meta
      analysis of randomised controlled trials of VNS, we estimate that six people
      require implantation in order for one person to experience a 50% reduction in
      seizure frequency. Costs averted from improved epilepsy control were ascertained
      from published literature. Values for health states were obtained from a series
      of 42 seizure clinic attenders using time trade-off techniques and the EQ-5D
      health status instrument. The cost per quality adjusted life year gained was
      estimated and the values obtained were tested in a sensitivity analysis. RESULTS:
      Improved epilepsy control averted, on average, 745 pounds sterling health care
      costs per annum. People with epilepsy had great difficulty performing the time
      trade-off experiment, but those who managed to complete the task valued a 50%
      reduction in their own seizure frequency at 0.285 units. For a programme of six
      implants, the baseline model estimated the cost per quality adjusted life year
      gained at 28,849 pounds sterling. The most favourable estimate was equal to 4785
      pounds sterling per quality adjusted life year gained, assuming that the number
      needed to treat was similar to published series in which one response was
      obtained for every three implants. The least favourable estimate was equal to
      63,000 pounds sterling per quality adjusted life year gained, when EQ-5D utility
      values were used. The cost per quality adjusted life year gained was not
      sensitive to changes in length of stay, nor complication rates, but was
      significantly influenced by cost of device and device battery life expectancy.
      CONCLUSION: There is not a strong economic argument against a programme of VNS
      implantation, although care should be taken to try and identify and treat those
      most likely to benefit.

PMID- 12810337
TI  - Lateralising value of ictal features in partial seizures: effect on postsurgical
      outcome.
AB  - We reviewed the videotapes of 49 consecutive patients with a history of medically
      refractory temporal lobe epilepsy for the presence and laterality of unilateral
      hand posturing (UHP), unilateral hand automatism (UHA), non-forced head turning
      (HT), and post-ictal dysphasia (PID). All of these patients underwent temporal
      resections with follow-up for more than 2 years after the surgery. We examined
      the correlation of consistency, frequency, and laterality of each of these signs
      on the postsurgical outcomes. The distribution of these signs was not
      significantly different between patients with Engel class 1 versus Engel class 2
      4. The consistency and laterality of these signs do not correlate with
      postsurgical outcomes.

PMID- 12810338
TI  - The Washington Psychosocial Seizure Inventory (WPSI): psychometric evaluation and
      future applications.
AB  - The Washington Psychosocial Seizure Inventory (WPSI) clinical scales were
      developed via an empirical item selection approach and have been used widely to
      measure aspects of psychosocial functioning of patients with epilepsy. However,
      these empirically derived clinical scales have not been assessed psychometrically
      using a modern item response theory-based model. The goals of this study were to:
      (1) evaluate how items in each clinical scale performed in such a way as to
      represent the underlying constructs being measured; and (2) derive a shorter
      version while maintaining measurement precision. WPSI item response data from 145
      adults with epilepsy collected for an evaluation study of an intervention to pact
      negative attributional style in epilepsy were used. The dichotomous Rasch model
      suitable for the true-false response choices was used to analyse each clinical
      scale separately. Most items within each scale fit the measurement model well,
      with very few exceptions. All items, therefore, were retained. A method, based on
      computerised adaptive testing (CAT), is offered for shortening the WPSI using a
      psychosocial outcomes item bank derived from the study. Individuals' specific
      levels of functioning are used to derive measures of their psychosocial
      functioning with a minimum number of items.

PMID- 12810339
TI  - Complex partial seizures of frontal lobe onset statistical analysis of ictal
      semiology.
AB  - OBJECTIVE: To identify the ictal semiology of complex partial seizures
      originating from the frontal lobe (FLCPS) and mesial temporal lobe (MTLE) in
      patients who became seizure free after surgery. METHODS: We analysed 149 seizures
      from 42 patients, 28 with MTLE (75 seizures) and 14 with FLCPS (74 seizures)
      seizure free for at least 1 year after surgery. Fifty-eight symptoms and signs
      were looked for in every seizure and their time of onset and ending noted.
      Statistical analysis was then used to define the frequency, time of onset and
      cluster analysis of these symptoms/signs. RESULTS: Epigastric aura was more
      frequent in MTLE while an aura of a general body sensation or indescribable
      feeling occurred only in FLCPS. Alimentary automatisms were more common and
      occurred earlier in MTLE (P<0.001). Perseverative automatisms, retching and
      vomiting occurred exclusively in MTLE while bicycling movements occurred only in
      FLCPS. Abdominal, psychic or olfactory aura followed by behavioural arrest,
      alimentary automatisms, repetitive distal upper extremity movements, complete
      loss of consciousness, looking around and whole body movements were typical of
      MTLE. Repetitive coarse upper extremity movements, complete loss of
      consciousness, complex motor and hypermotor activity were typical of FLCPS.
      CONCLUSION: The earliest symptoms and signs as well as their order of appearance
      allow one to distinguish between complex partial seizures arising from the
      frontal lobe and mesial temporal lobe.

PMID- 12810340
TI  - Use of clobazam for the treatment of refractory complex partial seizures.
AB  - Clobazam (CLB) add-on therapy was attempted in 183 patients with intractable
      complex partial seizures in whom conventional benzodiazepines had been
      successfully discontinued before initiation of CLB. Although complete remission
      was initially achieved in 61, tolerance developed in almost half (49.2%) within
      the first 3 months, whereas 23 out of 31 patients (74.2%) who remained seizure
      free for the first 3 months continued to be so over the next 3 months. CLB add-on
      therapy proved to be significantly more effective when concurrent GTC occurred
      more often than yearly. In the current series, no frank psychotic episodes were
      elicited among the 61 patients who achieved complete suppression of long-standing
      complex partial seizures, which was in agreement with previous studies. From
      these results, we believe that CLB is an effective, safe, and inexpensive
      medication for add-on therapy in difficult to treat focal epilepsies, especially
      without concurrent use of conventional benzodiazepine compounds.

PMID- 12810341
TI  - Non-epileptic seizures: patients' understanding and reaction to the diagnosis and
      impact on outcome.
AB  - RATIONALE: The study aim was to assess patients' understanding of and reaction to
      a diagnosis of non-epileptic attack disorder and to explore whether these factors
      contribute to outcome. METHOD: Eighty-four patients diagnosed with non-epileptic
      attack disorder participated in the study. Participants answered questions about
      their seizures and understanding and reaction to the diagnosis. Data were
      collected by semi-structured telephone interview. Questionnaires were sent to the
      patients' general practitioners (GPs) to gather information regarding the
      patient's seizure status, prescription of anti-epileptic drugs and opinion
      regarding the diagnosis. RESULTS: At the time of follow-up, a third of
      participants reported being seizure free. A total of 63% did not have a good
      understanding of the diagnosis, most were unclear about the precipitating factors
      and the most common reaction to the diagnosis was confusion. Many reported a
      negative impact of NES on everyday life. Sixty-five percent reported receiving
      psychological follow-up but the number of sessions attended was few (median 2).
      There was evidence that the reaction to the diagnosis contributed to the outcome
      in particular an angry outcome was associated with a poor prognosis. Ten GPs did
      not agree with the diagnosis. CONCLUSION: Patients understanding and reactions to
      a diagnosis of non-epileptic attacks are important factors that should contribute
      to the development of more tailored treatment approaches.

PMID- 12810342
TI  - Tilt table testing in patients referred from an epilepsy clinic.
AB  - OBJECTIVE: To assess the role of head up tilt testing (HUT) in diagnosing
      probable or possible vasovagal syncope (VVS) in patients referred from an
      epilepsy clinic. METHODS: One hundred thirty two patients underwent HUT over 36
      months. Complete data were available on 128 patients (52 male) aged 14-80 (mean
      36.7) years. The main indication for HUT (head up tilt at 70 degrees for 45
      minutes) was recurrent undiagnosed blackouts, likely to be VVS. Patients were
      divided, prior to knowledge of the HUT results, into probable VVS, possible VVS,
      or probable/possible VVS associated with definite epilepsy. RESULTS: HUT was
      positive in 72 patients (56%), and led to an alternative definite diagnosis in 31
      (24%). Diagnostic change was more likely in those provisionally labelled either
      as possible VVS (15 of 34; 44%) or as a combination of epilepsy with possible or
      probable VVS (12 of 19; 63%) compared to those with probable VVS (4 of 75; 5%;
      P<0.01).Of the 45 patients previously treated with antiepileptic medications 27
      did not have epilepsy. CONCLUSION: HUT has an important role in confirming or
      refuting the diagnosis of VVS in patients presenting with undiagnosed blackouts
      to an epilepsy clinic, and particularly so in patients with possible rather than
      probable VVS, and in those thought to have a combination of epilepsy and possible
      or probable VVS.

PMID- 12810343
TI  - Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA,
      glutamate, and glutamine concentrations.
AB  - The effects of antiepileptic drugs, gabapentin, pregabalin and vigabatrin, on
      brain gamma-aminobutyric acid (GABA), glutamate and glutamine concentrations were
      studied in Long Evans rats using proton magnetic resonance spectroscopy (MRS) of
      perchloric acid extracts. Cellular glutamate concentrations significantly
      decreased by 7% (P<0.05) 2 hours after intraperitoneal injection of 100mg/kg
      gabapentin and 4% (P<0.05) with 1000 mg/kg. No differences were observed in
      cellular GABA and cellular glutamine concentrations in rats treated with
      gabapentin. Pregabalin, an analogue of gabapentin, significantly decreased
      cellular glutamate concentrations by 4% (P<0.05), while no effect was observed on
      cellular GABA or glutamine concentrations in the healthy rat forebrain.
      Vigabatrin, used as a positive control to increase GABA levels, produced a 50%
      increase in cellular GABA compared to saline treated rats (P<0.003). Although,
      gabapentin and pregabalin are anticonvulsants designed to mimic GABA, these drugs
      do not raise cellular GABA levels acutely but modestly decreased cellular
      glutamate levels in our healthy rat forebrain model.

PMID- 12810344
TI  - Hamartomas and epilepsy: clinical and imaging characteristics.
AB  - PURPOSE: Cerebral hamartomas are lesions marked by a disorganized arrangement of
      mature neural elements and represent a rare cause of medically intractable focal
      epilepsy. We present the clinical presentation and imaging findings of this rare
      entity. METHODS: History and neurophysiological studies of 14 patients with
      pathologically confirmed hamartomas who had surgery for intractable focal
      epilepsy were reviewed. MRIs were available for review in 10 patients. RESULTS:
      The lesions were most commonly located in the temporal and frontal lobes. Seizure
      semiology was concordant with the anatomic location of the hamartoma in all
      patients. Nine of the thirteen patients (69%) with the hamartoma confined to one
      lobe had interictal spikes and sharp waves at the corresponding electrodes. The
      ictal pattern was confined to the same lobe of the hamartoma in five of nine
      patients with ictal recordings. Although imaging characteristics were variable,
      all patients had signal increase on T2-weighted images and 50% of them had mild
      mass effect. Neocortical involvement was present in the majority of patients
      (7/10), blurring of the gray/white matter interface was seen in seven patients.
      Five of those seven patients were found to have associated cortical dysplasia by
      pathology. CONCLUSION: Hamartomas represent a rare entity and may cause
      devastating epilepsy. Imaging characteristics are difficult to distinguish from
      those of some other developmental tumors. Hamartomas are frequently associated
      with microscopic cortical dysplasia (CD), thus underlining their malformative
      etiology.

PMID- 12810345
TI  - Cerebellar volume and long-term use of phenytoin.
AB  - OBJECTIVES: To perform MRI cerebellum volumetry in patients exposed to phenytoin
      and to identify factors associated with cerebellar atrophy (CA). METHODS: From
      100 consecutive epilepsy patients we selected those with phenytoin use for more
      than 2 months and with MRI scan available for volumetric studies. We obtained
      cerebellar volumes corrected for total intracranial volume. Volumes below 2
      standard deviations from the mean of control group were considered abnormal.
      RESULTS: We studied 56 patients (33 women). Mean age was 33.6 years and mean
      duration of epilepsy was 17.6 years. Mean daily dose of phenytoin was 301 mg. CA
      was detected in 20 (35.7%) patients. CA was not associated with frequent
      generalised seizures. CA correlated with duration of epilepsy (r=-0.34; P=0.01)
      and years of treatment with phenytoin (r=-0.48; P=0.001), but not with age and
      mean daily dosage of phenytoin (P>0.05). However, a multiple correlation analysis
      as well as a backward stepwise multiple regression analysis including all
      variables showed that only duration of treatment was significantly associated
      with CA (P=0.001). CONCLUSIONS: CA is frequently associated with long-term use of
      phenytoin. Although duration of epilepsy may have an influence in the CA, this is
      clearly less important than the time of exposure to phenytoin.

PMID- 12810346
TI  - The anticonvulsant effect of citalopram as an indirect evidence of serotonergic
      impairment in human epileptogenesis.
AB  - Some evidence would indicate that a serotonergic deficit may be involved in
      epileptogenesis. A preliminary trial of citalopram, a selective inhibitor of
      serotonin reuptake, was carried out. Citalopram 20mg/day was given to 11 non
      depressed patients with poorly controlled epilepsy as an add on treatment with an
      open label design for 8-10 months. The median seizure frequency dropped by 55.6%
      in the whole group, with nine patients improving by at least 50%. No adverse
      reactions occurred with the exception of mild drowsiness. There were no changes
      of post-treatment as compared to pre-treatment AED serum concentrations. Although
      controlled studies are required to confirm the anticonvulsant effect of
      citalopram, these findings may be regarded as an indirect evidence of
      serotonergic impairment in human epileptogenesis.

PMID- 12810347
TI  - Nonconvulsive status epilepticus due to a de novo contralateral focus during
      tiagabine adjunctive therapy.
AB  - We describe a 30-year-old woman with an infantile-onset epilepsy due to a left
      temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE)
      during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de
      novo right temporal focus not previously evident. After the i.v. administration
      of 4 mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal
      EEG abnormalities reappeared. To our knowledge this is the first case of
      paradoxical seizure exacerbation associated with TGB therapy in which the
      clinical and EEG features are congruous with a new contralateral focus.

PMID- 12810348
TI  - Effects of histamine on Th1/Th2 cytokine balance.
AB  - Atopic asthma is a chronic inflammatory disorder of the airways where upon
      exposure to allergens, the body mounts an immune response. This disease is
      associated with an increase in the number of Th2 (T helper type 2) cells and Th2
      cytokines and a decrease in the number of Th1 (T helper type 1) cells and Th1
      cytokines. Histamine plays an important role in the pathogenesis of atopic asthma
      through differential regulation of T helper lymphocytes. Histamine enhances the
      secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13
      and inhibits the production of Th1 cytokines IL-2 and IFNgamma (interferon-gamma)
      and monokine IL-12. It has been shown that histamine can modulate the cytokine
      network through upregulation of PGE(2) (prostaglandin E(2)) and NO (nitric
      oxide). Histamine also affects cytokine production via H2 receptors and through
      the activation of PKA (protein kinase A). We have also demonstrated that the Jak
      STAT (Janus kinase-signal transducers and activators of transcription) pathway is
      involved in histamine-mediated regulation of Th2 cytokines IL-5, IL-10, IL-13 and
      Th1 cytokine IFNgamma. While standard treatment of asthma consists of beta
      receptor agonists and inhaled corticosteroids, the elucidation of histamine's
      control over the cytokine network and the Th1/Th2 balance provides a basis for
      the potential use of antihistamines in the prevention and treatment of atopic
      asthma. Several other anti-allergic agents to modulate the Th1/Th2 balance are
      under current investigation based on this paradigm. These include cytokines,
      cytokine antagonists, anti-IgE, and vaccinations. As more advances are made in
      our understanding of histamine and its control over the Th1/Th2 balance, the use
      of new therapeutic targets such as these will play a prominent role in disease
      management.

PMID- 12810349
TI  - Modulation of CD(4)(+) and CD(8)(+) tumor infiltrating lymphocytes by a fraction
      isolated from shark cartilage: shark cartilage modulates anti-tumor immunity.
AB  - Shark cartilage has proven to have some inhibitory effects on angiogenesis,
      metastasis, cell adhesion and proteolysis. In this study, we wanted to study some
      of the effects of shark cartilage on tumor immune response. Firstly, by means of
      chromatographic methods and delayed type hypersensitivity (DTH) test, we
      optimized a procedure for isolation and purification of a shark cartilage protein
      fraction with most immunostimulatory effects. Then, we examined its effect on the
      infiltration of CD(4)(+) and CD(8)(+) lymphocytes into a murine tumor model. Our
      fraction was composed of two major proteins with molecular weights (MWs) of about
      14 and 15 kDa. This fraction highly increases DTH response against sRBC in mice.
      Furthermore, intraperitoneal injection of this fraction to tumor-bearing mice
      could increase T-cell infiltration into the tumor. Also, there was a significant
      increase in the CD(4)/CD(8) ratio in tumor infiltrating lymphocytes, but no such
      changes were found in the peripheral blood lymphocytes. According to these
      results, we suppose that this fraction is a good candidate for further studies in
      cancer therapy. Also, we concluded that this fraction, with previously proven
      anti-angiogenic effects, can augment cellular immune response and T-cell
      infiltration into the tumor and thus, there may be a direct relationship between
      angiogenesis inhibition and T-cell infiltration.

PMID- 12810350
TI  - Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity.
AB  - Apoptosis plays an important role in immune responses, but little is known about
      its involvement in contact hypersensitivity (CH). In this study, we have
      investigated the role of Fas/Fas ligand (FasL)-mediated apoptosis in the
      pathogenesis of CH. Mice were sensitized by one topical application of 100 microl
      of 3% oxazolone to shaved skin of the abdomen. Six days later, CH was provoked by
      challenging both sides of sensitized mouse right ear with 15 microl of 1%
      oxazolone. Using a DNA ladder assay, we found that apoptosis was induced in the
      skin of oxazolone-sensitized mice 24-96 h after allergen challenge. Annexin V
      fluorescein isothiocyanate (FITC)-propidium iodide (PI) apoptosis flow cytometric
      assay showed that early apoptotic CD4(+) T cells (annexin V-FITC(+)PI(-)), but
      not late apoptotic CD4(+) T cells (annexin V-FITC(+)PI(+)), increased in the
      inflamed skin of mice with CH. Moreover, the expressions of mRNAs for T helper
      (Th2) cytokine (interleukin (IL)-4), Th1 cytokine (interferon (IFN)-gamma) and
      proapoptotic molecules (Bax, Fas, FasL and IL-1beta-converting enzyme
      (ICE)/caspase-1) were significantly elevated in the oxazolone-sensitized mouse
      skin 6-72 h after allergen challenge. Dramatic increase in IL-10 mRNA was only
      observed in the sensitized mouse skin 6 and 12 h after allergen challenge.
      Furthermore, CH was significantly inhibited with decreased apoptosis and early
      apoptotic CD4(+) T cells in inflamed skin in Fas mutant lpr/lpr mice compared to
      wild-type mice, whereas there were no significant differences in IL-4, IFN-gamma,
      IL-10, Bax and ICE mRNAs in the inflamed skin of CH between lpr/lpr and wild-type
      mice. Our results thus suggest that Fas/FasL pathway partially contributes to
      apoptosis in murine CH and that Fas/FasL-mediated apoptosis plays a partial role
      in the development of CH. The contribution of Fas/FasL-mediated apoptosis to CH
      appears independent of Th1 and Th2 cytokines.

PMID- 12810351
TI  - Intestinal tissue kallikrein-kallistatin profile in inflammatory bowel disease.
AB  - The profile of tissue kallikrein (TK) and its inhibitor, kallistatin was
      evaluated in patients with active ulcerative colitis (UC) and Crohn's disease
      (CD). Tissue kallikrein is mainly localized to goblet cells and kallistatin to
      epithelial cells of human intestine. Intestinal tissue kallikrein (ITK) and
      kallistatin are significantly decreased in inflamed intestine compared to
      noninflammatory controls. TK mRNA as well as kallistatin mRNA is significantly
      decreased in intestinal biopsy samples from UC-active patients compared with
      controls. The difference in distribution and levels of ITK and kallistatin in
      protein and mRNA in patients with inflammatory bowel disease (IBD) compared to
      controls suggest a role in inflammatory state.

PMID- 12810352
TI  - Maternal immune stimulation reduces both placental morphologic damage and down
      regulated placental growth-factor and cell cycle gene expression caused by
      urethane: are these events related to reduced teratogenesis?
AB  - Activation of the maternal immune system in mice decreased cleft palate caused by
      the chemical teratogen, urethane. Direct and indirect mechanisms for this
      phenomenon have been suggested, including maternal macrophages that cross the
      placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins
      (cytokines) that cross placenta to alleviate or partially alleviate toxicant
      mediated effects in the developing fetus. A third mechanism to explain improved
      fetal developmental outcome in teratogen-challenged pregnant mice might involve
      beneficial effects of immune stimulation on the placenta. In the present
      experiments, urethane treatment altered placental morphology and impaired
      placental function, the latter indicated by down-regulated activity of cell cycle
      genes and of genes encoding cytokines and growth factors. Maternal immune
      stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma
      (IFNgamma) reduced morphologic damage to the placenta caused by urethane and
      normalized expression of several genes that were down-regulated by urethane.
      Urethane treatment also shifted placental cytokine gene expression toward a T
      cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2
      profile that may be more beneficial to pregnancy and fetal development. These
      data suggest that the beneficial effects of maternal immune stimulation on fetal
      development in teratogen-exposed mice may, in part, result from improved
      placental structure and function.

PMID- 12810353
TI  - Tissue-dependent effects of immunization with a nicotine conjugate vaccine on the
      distribution of nicotine in rats.
AB  - Vaccination of rats against nicotine reduces nicotine distribution to brain even
      at nicotine doses greatly exceeding the estimated binding capacity of the
      available antibody. This observation suggests a differential effect by which
      vaccination reduces nicotine distribution to brain to a greater extent than to
      other tissues. To test this hypothesis, vaccinated rats received a single
      intravenous nicotine dose equal to twice the estimated binding capacity of
      nicotine-specific antibody in vaccinated rats. The total and bound serum nicotine
      concentrations were higher in the vaccinated rats compared to controls, while the
      unbound serum nicotine concentration was lower. Distribution of nicotine to brain
      was reduced in vaccinated rats in a time-dependent manner, with a greater
      reduction at 1 min (64%) than at 25 min (45%). Vaccination reduced nicotine
      distribution to muscle, testis, spleen, liver, heart, and kidney, but to a lesser
      extent than to brain, while nicotine distribution to fat was increased.
      Chronically infused nicotine showed a similarly altered pattern of tissue
      distribution in vaccinated rats, but differences were in general smaller than
      after a single nicotine dose; brain nicotine concentration was 24% lower in
      vaccinated rats, while lung nicotine concentration was higher. The presence of
      nicotine-specific antibody in tissues may have contributed to the increased
      nicotine concentrations in fat and lung. These data suggest that vaccination
      reduces nicotine distribution to brain not only by sequestering nicotine in serum
      but also by redirecting tissue distribution disproportionately away from brain,
      such that nicotine concentrations are reduced to a greater extent in brain than
      in other tissues.

PMID- 12810354
TI  - The antiplatelet activity of Geiji-Bokryung-Hwan, Korean traditional formulation,
      is mediated through inhibition of phospholipase C and inhibition of TxB(2)
      synthetase activity.
AB  - Geiji-Bokryung-Hwan (GBH), consisting of herbes of Cinnamomi ramulus (Geiji),
      Poria cocos (Bokryun), Mountan cortex radicis (Mokdanpi), Paeoniae radix
      (Jakyak), and Persicae semen (Doin), on antiplatelet activity in human platelet
      suspensions was studied. The mechanism involved in the antiplatelet activity of
      GBH in human platelet suspensions was investigated. GBH did not significantly
      affect the thromboxane synthetase activity of aspirin-treated platelet microsomes
      and GBH (15 and 30 microg/ml) significantly inhibited [3H]arachidonic acid
      released in collagen-activated platelets but not in unactivated-platelets. Nitric
      oxide (NO) production in human platelets was measured by a chemiluminesence
      detection method in this study. GBH did not significantly affect nitrate
      production in collagen (10 microg/ml)-induced human platelet aggregation. Various
      concentrations of GBH (0, 5, 10, 15, and 30 microg/ml) dose-dependently inhibited
      [3H]inositol monophosphate formation stimulated by collagen (10 microg/ml) in
      [3H]myoinositol-loaded platelets at different incubation times (1, 2, 3, and 5
      min). These results indicated that the antiplatelet activity of GBH may possibly
      be due to the inhibition of phospholipase C (PLC) activity, leading to reduce
      phosphoinositide breakdown, followed by the inhibition of thromboxane A(2)
      formation, and then inhibition of [Ca(2+)](i) mobilization of platelet
      aggregation stimulated by agonists. In conclusion, GBH suppressed PLC in a dose
      dependent manner, and may have pharmaceutical applications. These data suggest
      that GBH extracts merit investigation as a potential anti-atherosclerogenic agent
      in humans.

PMID- 12810355
TI  - Effect of total secondary carotenoids extracts from Chlorococcum sp on
      Helicobacter pylori-infected BALB/c mice.
AB  - Helicobacter pylori is a human pathogen associated with type B gastritis, peptic
      ulcer disease and gastric cancer. A high intake of carotenoids has been suggested
      to prevent development of gastric malignancies. Microalgae Chlorococcum sp. could
      accumulate secondary carotenoids under stress conditions. The aim of the present
      study was to investigate whether dietary cell extract of Chlorococcum sp. could
      affect the bacterial load of H. pylori infected BALB/c mice and whether it could
      induce modulation of cytokine production. BALB/c mice were infected with H.
      pylori three times at 2-day intervals. Two weeks later, they were orally fed with
      cell extract of Chlorococcum sp. for the following 2 weeks. Animals were killed
      at the end of the experiments. Stomachs were removed and paraffin sections were
      stained for histology examination. Splenocytes were obtained and cultured in
      vitro with H. pylori sonicate to evaluate induction of interferon gamma (IFN
      gamma) and interleukin 4 (IL-4) secretion. Mice treated with carotenoids-rich
      algal meal showed significantly reduced bacterial load and gastric inflammation.
      These changes were associated with a shift of the T-lymphocytes response from a
      predominant T helper type 1 (Th1) response dominated by IFN-gamma to a Th1/Th2
      response with IFN-gamma and IL-4.

PMID- 12810356
TI  - Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in
      stable renal transplant patients: evaluation of long-term target C(2).
AB  - We investigated the relationship between the pharmacokinetics and
      pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order
      to define an effective and safe therapeutic range. The area under the curve of
      the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median
      values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a
      strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with
      C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively).
      Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing
      significant reductions (82% and 89.6%, respectively; p<0.0005) compared with
      normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml
      at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions
      of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1
      pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1%
      reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation
      between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537,
      p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030,
      r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's
      p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701)
      production. In treated patients, the Emax inhibitory sigmoidal model showed that
      a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF
      gamma production. The results demonstrated a significant inhibition of
      calcineurin activity and IL-2 and IFN-gamma production in patients receiving
      cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384
      ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN
      gamma synthesis, and the lack of rejection episodes and relevant toxicity.

PMID- 12810357
TI  - Inhibitory effects of deer antler aqua-acupuncture, the pilose antler of Cervus
      Korean TEMMINCK var mantchuricus Swinhoe, on type II collagen-induced arthritis
      in rats.
AB  - Water extract of deer antler aqua-acupunture (DAA) prepared from the growing
      antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe, was used to
      investigate the efficacy of a traditional immunosuppressive and immuno-activating
      Korean aqua-acupuncture, on the development of type II collagen (CII)-induced
      arthritis (CIA) in rats. The onset of arthritis was observed at the 24th day
      after the CII-immunization in rats, and the severity of CIA was gradually
      developed. As compared with rats treated with saline, DAA i.p. injected at doses
      of more than 50 microg/kg once a day for 14 days inhibited the ability of
      inguinal lymph node cells to produce T cell cytokines interleukin 2 and
      interferon-gamma when the cells were obtained from rats 24 days after
      immunization and cultured in vitro with CII. Treatment with DAA also inhibited
      the production of macrophage cytokines interleukin-1beta, IL-6 and tumor necrosis
      factor alpha in response to in vitro stimulation of lymph node and macrophage
      cells with CII. In addition, in order to evaluate the influence of DAA on the
      incidence and development of arthritis in rat CIA, rats were immunized twice at a
      3-week interval with bovine CII, with DAA being given i.p. once a day for 14 days
      with four different regimens. A 14-day course of DAA treatment at a daily dose of
      100 microg/kg, which began on the day of the first CII immunization, suppressed
      the development of arthritis, as well as antibody formation and delayed-type
      hypersensitivity to CII. Treatment with DAA, which started on the same day as the
      booster immunization, also resulted in inhibition of development of arthritis and
      of immune responses to CII. However, treatment with DAA, which was
      prophylactically started prior to a primary immunization, did not inhibit the
      development of arthritis and immune response to CII. Furthermore, DAA extract did
      not affect the established diseases.

PMID- 12810358
TI  - Cocaine increases inducible nitric oxide synthase expression in rats: effects of
      acute and binge administration.
AB  - The present studies assessed the effects of acute and binge cocaine
      administration on the in vivo production of inducible nitric oxide synthase in a
      rat model of endotoxemia. Inducible nitric oxide synthase is a key enzyme
      involved in host defense and inflammatory responses consequent to infection
      through its production of nitric oxide. Male Lewis rats received subcutaneous
      injections of saline or selected doses of cocaine (7.5-30 mg/kg) at the same time
      as a 50 microg/kg dose of lipopolysaccharide (LPS). Animals in the binge cocaine
      experiments received two additional injections of cocaine or saline at 2 and 4 h
      after the initial injections. All animals were sacrificed 6 h after initial drug
      administration and tissues harvested for determination of iNOS protein levels.
      Plasma nitrite/nitrate levels were also assayed to assess any treatment-related
      differences in the degradative by-products of nitric oxide metabolism. Western
      blot analyses of iNOS expression indicated that both acute and binge cocaine
      treatment resulted in significant increases in iNOS expression in all tissues
      assayed. Furthermore, acute and binge cocaine treatment also dose-dependently
      increased plasma nitrite levels. These data suggest that cocaine may impact
      resistance to gram-negative infections and severity of these infections via
      modulation of nitric oxide parameters.

PMID- 12810359
TI  - Dopamine inhibits cytokine release and expression of tyrosine kinases, Lck and
      Fyn in activated T cells.
AB  - The effect of dopamine (DA) on the release of cytokines from activated human T
      cells has been evaluated to analyze the mechanism by which physiological
      concentration of dopamine inhibits T cell proliferation. Dopamine inhibited anti
      CD3 mAb-induced release of both Th1 and Th2 cytokines, IL2, IFN-gamma and IL4
      from T cells by specific class of dopamine receptors. This action of dopamine was
      mediated by a new mechanism. Dopamine suppressed non-receptor tyrosine kinases,
      Lck and Fyn expression which are the initial and pivotal signaling steps in T
      cell receptor (TCR) mediated different down stream signaling cascades, leading to
      cytokine release and subsequent clonal expansion of these immune effector cells.

PMID- 12810360
TI  - Effect of a traditional Chinese herbal medicine, Ren-Shen-Yang-Rong-Tang
      (Japanese name: Ninjin-Youei-To), on oligodendrocyte precursor cells from aged
      rat brain.
AB  - Understanding of oligodendrocyte precursor cells and their role in the generation
      of oligodendrocytes in developing and adult rodents has been considered,
      particularly much less is known about aged-rodent oligodendrocyte precursor cells
      and their cell lineage. In this present study, we have developed oligodendrocyte
      cultures from the 30-month-old rat brain and examined whether oligodendrocyte
      precursor cells can proliferate in vitro. Adult oligodendrocyte precursor cells
      (O1(-), O4(+)) and oligodendrocytes (O1(+), O4(+)) are present in the cultures of
      the 30-month-old rat brain. They are also capable of proliferating and
      differentiating in the cultures. These capabilities increased four- to fivefold,
      when the aged rats are treated with Ninjin-Youei-To for 3 months in comparison
      with those of control aged rats. These results suggest that Ninjin-Youei-To has a
      potential mitotic effect on oligodendrocyte precursor cells in aged-rat brains
      and may be expected to have a therapeutic effect on brain aging.

PMID- 12810361
TI  - The effect of aerial parts of Echinacea on the circulating white cell levels and
      selected immune functions of the aging male Sprague-Dawley rat.
AB  - Echinacea is one of the most widely used over-the-counter herbal preparations
      that purport to "improve immune system function", especially when taken as a
      short course of therapy (6-8 weeks). Since many purchasers are older individuals,
      a double-blind, placebo-controlled study was performed to investigate whether
      Echinacea could affect total and differential white cell counts, phagocytic
      activity and interleukin (IL-2) levels in 12-month-old, healthy, male Sprague
      Dawley rats when administered over an 8-week period. Echinacea (50 mg/kg of
      aerial parts) mixed with peanut butter or peanut butter alone was fed to 16 rats,
      which were receiving regular food and water ad libitum. Cell counts and immune
      functions were determined on rat tail vein blood on a weekly basis. Echinacea
      significantly increased circulating total white cell counts during the first 2
      weeks of administration, and IL-2 levels during the final 5 weeks of the study
      period (p<0.05). Differential counts were altered during the entire 8-week study,
      with mononuclear cells significantly increased to the detriment of granulocytes
      (p<0.05). No such changes were observed in animals given peanut butter alone. No
      difference was observed in phagocytic function between animals given Echinacea or
      peanut butter alone. These studies suggest that aerial components of Echinacea
      affect both mononuclear cell levels and circulating IL-2 levels in older animals.

PMID- 12810362
TI  - [Current problems in the data acquisition of digitized virtual human and the
      countermeasures].
AB  - As a relatively new field of medical science research that has attracted the
      attention from worldwide researchers, study of digitized virtual human still
      awaits long-term dedicated effort for its full development. In the full array of
      research projects of the integrated Virtual Chinese Human project, virtual
      visible human, virtual physical human, virtual physiome, and intellectualized
      virtual human must be included as the four essential constitutional opponents.
      The primary importance should be given to solving the problems concerning the
      data acquisition for the dataset of this immense project. Currently 9 virtual
      human datasets have been established worldwide, which are subjected to critical
      analyses in the paper with special attention given to the problems in the data
      storage and the techniques employed, for instance, in these datasets. On the
      basis of current research status of Virtual Chinese Human project, the authors
      propose some countermeasures for solving the problems in the data acquisition for
      the dataset, which include (1) giving the priority to the quality control instead
      of merely racing for quantity and speed, and (2) improving the setting up of the
      markers specific for the tissues and organs to meet the requirement from
      information technology, (3) with also attention to the development potential of
      the dataset which should have explicit pertinence to specific actual
      applications.

PMID- 12810363
TI  - Construction of dataset for Virtual Chinese Male No.1.
AB  - OBJECTIVE: To establish digitized Virtual Chinese Human Male No.1 (VCH-M1) image
      dataset with a 0.2-mm equal interval. METHODS: The body of a 24-year-old male was
      used for this study. Perfusion with phenol and vermilion of the arteries was
      performed, followed by body shape adjustment by cold saline and pre-embedding
      with broken ices in an upside-down position, which was completed in a stepwise
      procedure to minimize body shape deformation. Section milling was conducted
      subsequently with the section thickness of 2 mm and the section images were
      captured by digital camera, which were immediately transferred to a computer for
      storage and processing. RESULTS: A total of 9 232 sections were obtained for the
      whole body, and the resolution of each of the image in TIF format was 3 024x2 016
      pixels, resulting in the size of approximately 18 M for each image and about 161
      G for the whole dataset. CONCLUSIONS: Compared with VCH-F1, the image quality in
      VCH-M1 dataset is significantly improved, demonstrated by much clearer tissue
      boundary in the images and minimized body shape deformation during the embedding
      process.

PMID- 12810364
TI  - [Improvement of specimen sectioning technique for Virtual Chinese Human study].
AB  - OBJECTIVE: To improve the image quality of the specimen serial sections for
      establishing the Virtual Chinese Human dataset and to extend the durability of
      the milling tools. METHOD: The image quality of the serial sections obtained by
      using tangential and radial indexable milling tools was compared. RESULTS AND
      CONCLUSION: Compared with radial milling tools, tangential ones were more
      suitable for use in this study to ensure high-quality section image acquisition,
      showing the advantages such as high efficiency, long durability and low cost.

PMID- 12810365
TI  - [Three-dimensional reconstruction of the knee joint of digitized Virtual Chinese
      Male No.1 by finite element simulation].
AB  - To provide a three-dimensional (3D) model of the knee joint of digitized Virtual
      Chinese Male No.1 for finite element simulation, the digitized image data of the
      serial sections of the virtual human knee joint were imported to a computer for
      3D reconstruction using Mimics software after image segmentation and
      registration. Surface smoothing of the reconstructed model was performed with
      FreeForm system and transformation to IGES format executed. Following these
      procedures, the 3D model of IGES format of knee point was reconstructed, which
      can be used for finite element simulation.

PMID- 12810366
TI  - [Establishment of Internet-based database of the Virtual Chinese Human dataset].
AB  - To establish an Internet-based database for the dataset of Virtual Chinese Human
      that is accessible to the interested researchers, modifications and compression
      of the original VCH-format dataset of Virtual Chinese Human were performed before
      it was uploaded to the server, and RAID0+1 storage technology was adopted with
      specific download accesses designed for different users. After dataset
      modification and compression, the data size was considerably reduced to allow
      convenient data storage and transfer. The RAID0+1 storage technology guarantees
      the security and high-speed download of data through different means established.
      Internet-based database provides important accesses for sharing the achievement
      in virtual human study between world-wide researchers, which has been imperative
      in the present situation of science development.

PMID- 12810367
TI  - [Registration of the image data of the Virtual Chinese Female No.1].
AB  - In this study, the authors attempt to find a solution for the image registration
      before three-dimensional reconstruction of digitized Virtual Chinese Female No.1
      (VCH-F1) image data can be completed. On the basis of a thorough understanding of
      the features of the image data, the parameters were determined based on the
      marker outside the specimen and the least-square procedure performed on the
      outline offset distance between two images, prior to the completion of the image
      registration by means of rigid body transformation with the parameters. In the
      trial application of these two methods in image registration for these image
      data, good results were obtained, which approved of the application of the two
      methods for accomplishing the image registration with simpler calculation
      processes and easier computer processing.

PMID- 12810368
TI  - [Differential diagnosis of severe acute respiratory syndrome (SARS) in "post
      SARS" stage].
AB  - The epidemic of severe acute respiratory syndrome (SARS) has now been brought
      under control and entered the so-called post-SARS stage, with only a very few new
      cases reported daily throughout China. As an infectious disease spreading through
      the respiratory tract, SARS is featured by the inconsistency between its clinical
      representations, physical signs of the lungs and chest imaging findings. It has
      been shown that atypical pneumonia (AP), with similar clinical features to SARS,
      has been identified in Guangzhou, China, long before the prevalence of SARS, a
      fact that urges further understanding of SARS in regard to its incidence and
      variable clinical courses, for its differential diagnosis with such diseases as
      AP, influenza-related pneumonia, pulmonary tuberculosis, fungal and
      cytomegalovirus pneumonia. Information sharing among the medical institutes and
      training of the first-line medical staff for their better understanding and
      awareness of SARS and AP is crucial in the clinical practice, to insure timely
      case identification and avoid "oversensitive" diagnosis. Consultation of
      particular cases involving experts from multiple medical science fields should be
      encouraged, which is also an effective measure against newly emerged infectious
      diseases.

PMID- 12810369
TI  - [Construction and identification of the cDNA phage expression library for human
      colorectal cancer antigens].
AB  - OBJECTIVE: To construct a cDNA phage expression library for human colorectal
      carcinoma antigens. METHODS: After the total RNA was extracted from human
      colorectal cancer tissues, the single-strand and double-strand cDNA were
      synthesized through reverse transcriptase PCR and long-distance PCR, with the
      cDNA fragments smaller than 500 bp removed and the remaining cDNA combined with
      the right and left arms of dephosphorylated lambdaTriplEx2 phage vector. The
      recombinant phage were then packaged in vitro by MaxPlax Packaging extract, and a
      small portion of the packaged phage was used to infect E.coli XL1-Blue. Titer
      measurement was performed so as to determine the capacity of the library. SfiI
      restriction endonucleases was used to cut the recombined phage DNA in order to
      identify the size of inserted cDNA. RESULTS: The constructed cDNA phage
      expression library for human colorectal cancer antigens consisted of 2.39 x 10(6)
      pfu/ml bacteriophages with a recombination rate of 97.5% and the length of the
      inserted cDNA fragment ranged from 600 to 4,000 bp with an average of 1,400 bp.
      CONCLUSION: The cDNA phage expression library of human colorectal cancer antigens
      is successfully constructed to meet the currently recognized standards, and can
      be well applicable in screening cDNA-cloned genes of human colorectal cancer
      associated antigens by immunoscreening.

PMID- 12810370
TI  - [Effect of human hair keratin implant on oligodendrocyte proliferation and
      differentiation in rats with acute spinal cord injury].
AB  - OBJECTIVE: To investigate the changes of oligodendrocyte proliferation and
      differentiation in response to implantation of degradable human hair keratin
      (HHK) into the spinal cord with acute injury in adult rats. METHOD: Rat models of
      acute spinal cord injury were established by direct impact of the exposed spinal
      cord with a weight-dropping device, 12 of which received immediate HHK implant
      into the injured spinal cord. The rats of control injury group (n=12) were
      subjected to the injury but did not receive subsequent implant, and those in sham
      operation group (n=12) only had the spinal cord exposure without injury. Another
      8 rats were used as the normal control group. Samples of the spinal cord were
      obtained 1, 4, 12, and 26 weeks respectively after the operations and serial
      sections were prepared for examination with light and electron microscope.
      RESULTS: One week after the injury, few oligodendrocytes were observed among the
      large number of the infiltrating leukocytes in the injured spinal cord with HHK
      implants. Staining with hematoxylin eosin and Mallory's phosphotungstic acid
      hematoxylin at the fourth week revealed oligodendrocyte proliferation around the
      HHK implant. The period from the 12th to 26th week was characterized by nerve
      regeneration and myelin sheath reconstruction, in the course of which empty
      cavity occurred within the sheath of the oligodendrocytes, and lamellar
      separation of the myelin sheath were observed. Phagocytized myelin sheath and
      axone fragment were detected in oligodendrocytes, with the newly generated
      oligodendrocytes scattering abound the rebuilt myelin sheath. CONCLUSION: HHK can
      be beneficial for the proliferation and differentiation of oligodendrocytes and
      myelin sheath rebuilding and repair in the course of neuronal regeneration after
      acute spinal cord injury.

PMID- 12810371
TI  - [Proliferation of retrorsine-treated SD rat immortalized hepatocytes after
      intrasplenic transplantation].
AB  - OBJECTIVE: To investigate the effect of retrorsine on the proliferation of SD rat
      immortalized hepatocytes after intrasplenic transplantation. METHODS:
      Immortalized hepatocytes from SD rats was prepared by transfecting the primary
      hepatocytes with a retroviral vector SSR69 expressing the genes encoding Simian
      virus 40 T large antigen. Twenty-four adult SD rats were randomly assigned to 3
      equal groups designated respectively as A, B, and C groups. Intraperitoneal
      retrorsine injections at the dose of 26 mg/kg.b.w. were performed twice in groups
      A and B at the interval of two weeks before hepatocyte transplantation. After 20%
      hepatic lobe resection were completed in all the groups, groups A and C received
      intraplenic transplant with immortalized hepatocytes, while group B received
      normal hepatocyte transplant. Post-mortem examinations were performed on the
      spleen samples with HE staining. Albumin expression in the transplanted
      hepatocytes was examined by immunohistochemical staining, and the ultrastructure
      of the transplanted cells was observed under transmission electron microscope.
      RESULTS: Histological examination demonstrated that the rat spleens in all the 3
      groups contained cluster of transplanted hepatocytes from 1 week to 3 weeks after
      the transplantation, and the proliferation of the transplanted cells were
      comparable between groups A and B, but both of which showed significant
      difference from group C. Albumin excretion by the immortalized hepatocyte was
      identified in all the groups, and the transplanted immortalized cells preserved
      normal cell ultrastructure. CONCLUSION: Immortalized hepatocytes of SD rat have
      the normal cell ultrastructure and albumin-excretion function, and retrorsine can
      promote the proliferation of the transplanted hepatocytes.

PMID- 12810372
TI  - [Recombinant Helicobacter pylori urease B subunit and its biological properties].
AB  - OBJECTIVE: To perform genetic recombination of the urease B subunit (UreB) of
      Helicobacter pylori (Hp) and examine the biological properties of the recombinant
      protein. METHODS: The gene fragment encoding Hp UreB was isolated clinically from
      Chinese subjects by means of PCR, and cloned subsequently into an expression
      vector pET-11C-UreB for the non-fusion protein expression in E.coli BL21 (DE3)
      strain. RESULTS: The expression of recombinant UreB was achieved in E.coli BL21
      with a relative molecular weight of approximately 62,000 at the expression ratio
      of 26%, and the first 15 amino acids of recombinant UreB were MKKISREYVSMYGP. The
      results of peptide mapping and amino acid compositional analysis were consistent
      with previous theoretical prediction, and enzyme-linked immunosorbent assay
      together with Western blotting indicated strong immunogenicity and reactivity of
      the recombinant protein in BalB/c mice, which were specifically recognized by
      polyclonal BalB/c mice anti-Hp sera or human sera infected with Hp. CONCLUSION:
      The results of this study has laid an solid immunological foundation for
      incorporating recombinant UreB as a subunit vaccine component against Hp.

PMID- 12810373
TI  - [Construction of recombinant adeno-associated virus carrying hepatitis B surface
      antigen gene and preliminary study of the gene expression and function].
AB  - OBJECTIVE: To construct recombinant adeno-associated virus (rAAV) carrying
      hepatitis B surface antigen (HBsAg) gene and study the function of the expressed
      HBsAg. METHODS: HBsAg gene (subtype ayw) was amplified from PTHBV-1 by PCR and
      cloned into the adeno-associated virus vector pSNAV to form the recombinant pSNAV
      HBsAg, which was transfected into BHK-21 cells by means of lipofectamine. Using
      G418 selection, a mixed cell line, BHK-HBsAg, was isolated, which was capable of
      HBsAg expression and was subsequently infected with HSV-1-HSV1-rc/Delta UL2 that
      was able to package the rAAV. After purification, rAAV-HBsAg was obtained. The
      expression of HBsAg in BHK-21 cells and 293 cells infected with rAAV-HBsAg were
      detected by enzyme-linked immunosorbent assay (ELISA), and the HBsAg antibodies
      in the sera of rAAV-HBsAg-immunized BalB/C mice were assayed by radio
      immunoassay. RESULTS: As detected by ELISA, the expressed HBsAg in mixed cell
      line mounted to 28.6+/-6.72 ng per 5 x 10(6) cells. The BHK-21 cells and 293
      cells infected with rAAV-HBsAg were both capable of HBsAg expression, the amount
      of which augmented with the increase of multiplicity of infection (MOI). BalB/C
      mice immunized with rAAV-HBsAg produced anti-HBsAg antibodies. CONCLUSIONS: rAAV
      HBsAg can induce humoral immune response against HBsAg and therefore can be a
      promising candidate hepatitis B vaccine, and in addition, it may serve the
      purpose of exploring possible immunotherapy for chronic HBV infection.

PMID- 12810374
TI  - [Methoxypolyethylene glycol-modified HLA-A2 antigen on lymphocytes].
AB  - OBJECTIVE: To modify the HLA-A2 antigen on the lymphocytes with
      methoxypolyethylene glycol (mPEG) so as to block the specific binding site for
      antibody. METHOD: Different types of mPEG (all with final concentration of 12
      mmol/L) were used at different temperatures in PBS with varied pH values for the
      modification of the HLA-A2 antigen. RESULT: The modification of the antigen was
      not obviously affected when it was carried out at 4 degrees Celsius or room
      temperature, but higher temperatures of 30 and 37 degrees Celsius significantly
      hampered the modification. Better antigen modification was observed with high
      concentration mPEG in basic PBS, depending also on the type of mPEGs used for
      this purpose. CONCLUSION: The specific HLA-A2 binding on the lymphocytes is
      completely blocked by benzotriazole carbonate-mPEG(mPEG-BTC), which is superior
      to N-hydroxysuccinimidyl ester of mPEG(mPEG-SPA). Maleimide-mPEG(mPEG-MAL) is
      incapable of blocking the HLA-A2 ligand-binding site with antibody.

PMID- 12810375
TI  - [Trabeculectomy with crescent tunnel knife under surface anesthesia for glaucoma:
      report of 41 cases].
AB  - This study aims to modify the surgical procedure of conventional trabeculectomy
      for glaucoma by incorporating scleral flap preparation with crescent tunnel knife
      under surface anesthesia. A total of 41 patients (48 eyes) received this modified
      surgical procedure, with the anesthesia being successfully implemented in all the
      cases. The time consumption by the operation on each eye averaged 17 min,
      shortened by 37% compared with the conventional procedure. The postoperative
      intraocular pressure was well under control without any complications arising
      either during or after the operation, showing the safety, rapidness and efficacy
      of this surgical approach in the treatment of glaucoma.

PMID- 12810376
TI  - [Effects of aging and hypoxia on the proliferation of cultured rat pulmonary
      arterial smooth muscle cells].
AB  - OBJECTIVE: To study the effects of aging and hypoxia on the proliferative
      behavior of cultured pulmonary arterial smooth muscle cells (PASMCs). METHODS:
      PASMCs isolated from aged (18-24 months) and young (3-4 months) rats were
      divided, according to the different treatments the cells were subjected to, into
      young and aged normoxic groups (groups A and B) and young and aged hypoxic groups
      (groups C and D) respectively. MTT cell proliferation assay, 3H-TdR incorporation
      assay, flow cytometriy and immunocytochemical analysis were respectively employed
      to observe the proliferative behavior. RESULTS: Compared with the cells from
      young rats, PASMCs from aged rats had a higher proliferation rate, more 3H-TdR
      incorporation, increased mitotic cell ratio, reduced amount of the total protein,
      and elevated content of proliferating cell nuclear antigen (PCNA). In comparison
      with normoxic condition, hypoxia elicited higher proliferation rate of the cells
      with inhibition of 3H-TdR incorporation that was subsequently increased. Higher
      percentage of mitotic cells, less total protein amount and increased PCNA were
      also observed in response to hypoxia. CONCLUSIONS: Aging and hypoxia may directly
      induce PASMC proliferation, and in aging PASMCs, the proliferation is the most
      obvious in response to hypoxic stimulation.

PMID- 12810377
TI  - [Relationship between aquaporin-4 expression in astrocytes and brain edema caused
      by glioma].
AB  - OBJECTIVE: To investigate the relationship between aquaporin-4 (AQP4) water
      channel expression in astrocytes and brain edema caused by glioma. METHODS: The
      changes of water transport in in vitro blood-brain barrier models were examined
      using high-performance liquid chromatography (HPLC), and the expression level of
      AQP4 was assayed by semiquantitative RT-PCR. RESULTS: The water transport of the
      in vitro blood-brain barrier model from the luminal side to basolateral side was
      increased after coculture with glioma cells, which induced significantly
      decreased expression level of AQP4 in the astrocytes. CONCLUSIONS: Glioma cells
      can promote water transport in in vitro blood-brain barrier model from the
      luminal side to abluminal side, and the brain edema induced by the glioma cells
      may not necessarily be the result of hyperpermeability of the blood-brain barrier
      to macromolecules in the plasma. The decreased expression level of AQP4 induced
      by glioma cells may be a molecular mechanism for neoplastic brain edema in
      patients with glioma.

PMID- 12810378
TI  - [Morphological changes of collagen fibrils during the formation of autogenous
      tendon induced by human hair keratin artificial tendon].
AB  - OBJECTIVE: To observe the morphological changes of collagen fibrils during the
      formation of autogenous tendon induced by human hair keratin (HHK) artificial
      tendon. METHODS: Rabbit models of injured tendon were established in which
      implantation of HHK artificial tendon was performed to observe the formation of
      autogenous tendon under light microscope and electron microscope at 3, 6, 9, 12
      and 16 weeks after HHK implantation. RESULTS AND CONCLUSION: During autogenous
      tendon formation induced by HHK artificial tendon, the tendon cells of the
      impaired end of the tendon and beneath the tendon membrane dedifferentiate and
      are capable of collagen secretion, followed by the formation of typesI,II and III
      collagen fibrils, and eventually, the majority of the tendon cells disappear with
      the collagenization of the tendon.

PMID- 12810379
TI  - [Expression of urotensinII in human coronary artery and coronary
      atherosclerosis].
AB  - OBJECTIVE: To assess the expression intensity of urotensinII (UII) in normal and
      atheromatous human coronary artery and explore its significance in coronary
      atherosclerosis. METHODS: Specimens of coronary arteries were obtained from 5
      normal subjects and the expression of human UII in the specimens was detected by
      immunohistochemical method. RESULTS: UII expression was found in the endothelial
      cells (ECs), foam cells (FCs), inflammatory cells (ICs) and intima smooth muscle
      cells (ISMs) of human coronary artery. Even in the normal coronary artery, UII
      expression could be detected immunohistochemically in the ECs, which, however,
      was characterized by higher UII expression levels in fatty streak lesions but by
      almost normal levels in fibrous and atheromatous plaque in the coronary artery.
      Enhanced UII expression was observed in FCs and ICs when fibrous plaque and
      atheromatous plaque developed in comparison with that in fatty streak lesions.
      The ISMs in all the lesions had mild UII immunoreactivity, but as the
      atherosclerosis exacerbated, the immunoreactivity tended to intensify.
      CONCLUSION: Human UII may regulate the functions of ECs, FCs, ICs and ISMs in the
      development and progression of coronary atherosclerosis.

PMID- 12810380
TI  - [Highly efficient construction of recombinant adenovirus containing double
      suicide gene driven by cytomegalovirus promoter using two-step CaCl2
      transformation method].
AB  - OBJECTIVE: To construct recombinant adenovirus containing double suicide gene
      driven by cytomegalovirus (CMV) promoter. METHODS: CD and TK gene were amplified
      by PCR and cloned into the shuttle vector pAdtrack CMV, and the resultant plasmid
      pAdtrack CMV-CDTK was linearized with PmeI and transformed into competent
      AdEasier-1 cells prepared by CaCl2 method. PacI digestion of identified
      recombinant plasmid DNA was performed before it was transected into 293 cells to
      package adenovirus, which was used to infect endothelial cells in vitro after
      adenovirus titer determination. RESULTS: Chemical transformation of linearized
      transfer plasmid into AdEasier-1 cells resulted in very high ratio (20/20) of
      positive clones of recombinant adenovirus containing. CD and TK fusion gene as
      confirmed by PCR test. CONCLUSION: The modified AdEasy system is more convenient
      and efficient for constructing recombinant adenovirus, which may facilitate
      further study of anti-tumor therapy targeting at the double suicide gene.

PMID- 12810381
TI  - [Role of antisense oligodeoxynucleotide of inducible nitric oxide synthase in the
      apoptosis and p-p38 MAPK signal transduction in rat neurons after spinal cord
      injury].
AB  - OBJECTIVE: To study the role of antisense oligodeoxynucleotides (ASODN) of
      inducible nitric oxide synthase (iNOS) on the apoptosis and p-p38 mitogen
      activated protein kinase (p-p38 MAPK) signal transduction of the neurons after
      spinal cord injury (SCI). METHODS: Antisense and non-sense oligodeoxynucleotides
      of iNOS were designed and synthesized, and injected into the subarachnoid space
      12 h before the compressive injury was given to the rat spinal cord. Reverse
      transcription-PCR and flow-cytometry were used to examine the iNOS mRNA
      expression and the apoptosis of the neurons within the injured spinal cord. The
      changes of p-p38 MAPK signal transduction pathway were detected by Western
      blotting. RESULTS: Obvious increase in iNOS expression and up-regulated p-p38
      MAPK were detected after SCI, and neuronal apoptosis was observed in the injured
      spinal cord. ASODN-iNOS treatment resulted in decreased expression levels of iNOS
      mRNA and p-p38 MAPK, and the neuronal apoptosis was alleviated. CONCLUSION: ASODN
      iNOS inhibits iNOS expression and neuronal apoptosis following SCI which may be
      related to the p-p38 MAPK signal transduction pathway.

PMID- 12810382
TI  - [Cloning of hepatitis C virus open reading frame sequence and non structural
      protein expressions of the virus].
AB  - OBJECTIVE: To induce the expressions of the constituent proteins of hepatitis C
      virus (HCV) using a vaccinia virus expression system. METHODS: The open reading
      frame (ORF) sequence encoding HCV large polyprotein precursor was cloned into a
      vaccinia virus promoter to construct the recombinant plasmid pVHCV, which was
      subsequently used, along with a control plasmid (pSC59) in a parallel experiment,
      to transfect BHK21 cells via Lipofectamine 2000 reagent, followed by infection of
      the cells with vTF7-3 vaccinia viruses. After a 48-h culture, the expressions of
      HCV nonstructural proteins NS3 and NS5a in the cells were detected using Western
      blotting and immunofluorescence assay. RESULTS: Western blotting analysis
      presented the nonstructural proteins NS3 and NS5a detected in pVHCV-transfected
      BKH21 cells as two bands with molecular weights of 70,000 and 56,000,
      respectively. In the immunofluorescence assay, intense granular fluorescence
      signal was detected in the cytoplasm of pVHCV-transfected cells, irrespective of
      the use of either NS3- or NS5a- specific mouse monoclonal antibody. CONCLUSION:
      HCV nonstructural proteins NS3 and NS5a can be expressed in BKH21 cells.

PMID- 12810383
TI  - [An experimental study of the implantation of an epitendineum-109 human hair
      artificial tendon complex in rabbits].
AB  - OBJECTIVE: To study the feasibility of in vivo implantation of an epitendineum
      109 human hair (109HH) artificial tendon composite. METHODS: An absorbable
      epitendineum-109HH artificial tendon complex was implanted into rabbits to
      observe its changes at different time points. In control groups, 109HH artificial
      tendons or the artificial tendon-Dacron complex were implanted instead. RESULTS
      AND CONCLUSION: and Conclusion The epitendieum-109HH artificial tendon complex
      was gradually but finally completely absorbed by the surrounding tissues to be
      replaced by normal tendon without conglutination or scar formation, approving the
      feasibility of the implantation of epitendineum-109 human hair artificial tendon
      complex in vivo.

PMID- 12810384
TI  - [Effect of tumor suppressor gene KAI1 on the biological behaviors of human
      colorectal carcinoma].
AB  - OBJECTIVE: To determine whether the expression of tumor suppressor gene KAI1 can
      suppress the invasive or metastatic ability of colorectal carcinoma cells.
      METHODS: KAI1 cDNA was transfected into highly malignant colorectal carcinoma
      cell line LoVo, which had low levels of endogenous KAI1 expression. The
      expressions of KAI1 mRNA and protein were determined by immunohistochemistry and
      in situ hybridization, and the biological behaviors of the KAI1-transfected LoVo
      cells were investigated by cell-cell adhesion, cell-matrix adhesion and invasion
      assays. RESULTS: KAI1 expression significantly suppressed the metastatic
      potential of KAI1-transfected LoVo cells, whose metastasis suppression was
      correlated with the increased adhesion to homotypic cells and reduced tumor
      adhesion to extracellular matrix components. KAI1 expression significantly
      suppressed the in vitro cell invasion in KAI1-transfected LoVo cells. CONCLUSION:
      KAI1 might function as inhibitor of colorectal carcinoma metastasis.

PMID- 12810385
TI  - [Discrepancy between the blood flow in hyperperfused epicardial coronary vessels
      and myocardial microcirculation following reperfusion: a study in canines].
AB  - OBJECTIVE: To investigate the hemodynamic changes in the epicardial coronary
      blood flow (ECBF) and myocardial microcirculation (MMC) during reactive hyperemia
      (RH) in response to reperfusion following 2-min ischemia in the left anterior
      descending coronary artery of canines. METHODS: Twelve adult mongrel dogs were
      used, whose left anterior descending coronary artery was separated and ligated
      for 2 min twice below the first branch. The heart rate, systolic blood pressure,
      diastolic blood pressure, mean blood pressure, ECBF and MMC were measured
      respectively before and after the ligation and at 5, 10, 15, 30, 45, 60, 90 and
      120 s after reperfusion. ECBF was determined with Doppler coronary flowmeter and
      MMC derived from the ultrasonic intensity measured by myocardial contrast
      echocardiography. RESULTS: During the course of RH, ECBF and MMC both evinced
      responses to hyperperfusion but in manners different in view of their hemodynamic
      changes, demonstrating the mismatch between them in this condition. ECBF
      exhibited a much higher peak flow increase than MMC. CONCLUSIONS: RH occurs in
      response to reperfusion after short-term (2 min) myocardial ischemia, when the
      discrepancy arises between ECBF and MMC. The primary mechanism might involve the
      recruitment of the capillaries and the opening of the shunt through the
      capillaries, and as a consequence, the myocardial perfusion is increased at the
      cost of decreased reserve of the coronary microcirculation.

PMID- 12810386
TI  - [Effect of tanshinone IIA on the growth behavior of human hepatoma cell line BEL
      7402 in vitro and its mechanism].
AB  - OBJECTIVE: To investigate the effect of tanshinone IIA on the growth behavior of
      human hepatoma cell line BEL-7402 in vitro and explore the mechanism. METHODS:
      Human hepatoma cell line BEL-7402 was exposed to tanshinoneIIA at different
      concentrations for 72 h, and the suppression of the cell growth was observed
      under inverted-phase contrast microscope. Apoptosis-related alterations in the
      cell morphology and biochemistry were examined under fluorescence microscope and
      transmission electron microscope (TEM) and by DNA agarose gel electrophoresis,
      and the apoptotic rate was quantified by flow cytometry (FCM). RESULTS: After
      treatment with 0-10 microg/ml tanshinone IIA for 72 h, the proliferation of BEL
      7402 cells was significantly suppressed, and cell apoptosis occurred
      characterized by cell shrinkage, nuclear chromatin condensation and
      fragmentation, formation of membrane blebs and apoptotic bodies as observed under
      fluorescence microscope and TEM. DNA ladder was presented in DNA electrophoresis.
      FCM analysis yielded the cell apoptotic rates of (20.78+/-2.17) %, (24.64+/-2.07)
      %, (31.47+/-3.86) %, (43.65+/-4.04) % and (52.36+/-3.75) % at tanshinone IIA
      concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 microg/ml respectively, all
      significantly higher than those of the control group [(2.37+/-0.29)%].
      CONCLUSION: Tanshinone IIA can inhibit the growth of human hepatoma BEL-7402
      cells possibly through the mechanism of apoptosis induction.

PMID- 12810387
TI  - [Quantitative study of bacteriological infections in dogs undergoing gunshot
      wound in seawater].
AB  - OBJECTIVE: To investigate the changes in bacterial proliferation and the time of
      infection occurrence in dogs wounded by gunshot in seawater. METHOD: Fourteen
      canine models of gunshot wound in seawater were established, with another 2 dogs
      receiving the wound without seawater immersion serving as control. Gross
      observation and quantitative bacterial analysis were performed at 0, 6, 12 and 24
      h after the injury respectively, and two dynamic models for the bacterial growth
      were set up on the basis of statistical analysis of the results. RESULTS:
      Bacterial quantity in both of the two groups tended to increase with time, but at
      each time point after the injury, the seawater group had higher bacterial count
      than the other group. Within 6 h after the injury, the bacterial count reached
      the critical point for clinical infection in seawater group. The two bacterial
      growth dynamics models were (1) Y=9.12 x 10(3+0.247X) and (2) Y=1.35 x
      10(3+0.227X) for the seawater group and land group respectively, with the variant
      X representing time after gunshot injury, and Y the bacterial count per gram
      tissue. Using the dynamic models, we found that to reach the same bacteria count,
      the land group needed 4 h more than the seawater group(4.2 h). CONCLUSIONS:
      Bacterial proliferation is accelerated in the wounds in seawater to result in
      earlier infection onset with more severity, suggesting that early debridement
      within 4 h after the injury, complete washing of the wound and early
      administration of the antibiotics are necessary for the wound management.

PMID- 12810388
TI  - [Purification of porcine pulmonary surfactant by CO2 supercritical fluid
      extraction].
AB  - OBJECTIVE: To develop a supercritical fluid extraction (SFE) method for purifying
      porcine pulmonary surfactant. METHOD: An orthogonal design with 4 factors and 4
      levels was used to optimize the SFE conditions. RESULTS: The best extraction
      conditions were established as the following: pressure 30 MPa, temperature 50
      degrees Celsius, dynamic extraction for 4 h with 0.2 ml ethanol as the modifier.
      CONCLUSION: The new method for purifying porcine pulmonary surfactant by SFE-CO2
      can cause drastic reduction of organic solvents, being convenient to use and
      effective to purify.

PMID- 12810389
TI  - [Significance of plasma 8-iso-prostaglandin F2alpha level in acute myocardial
      ischemia and intervention effect of N-acetylcysteine: a study in rats].
AB  - OBJECTIVE: To examine the correlation between 8-iso-prostaglandin F2alpha (8-iso
      PGF2alpha) levels in the plasma and myocardial tissue of rats with myocardial
      ischemia and observe the intervention effect of N-acetylcysteine (NAC), for the
      purpose of assessing the value of 8-iso-PGF2alpha in estimating the extent of
      free radical damage and implementing possible interventions. METHODS: Forty-five
      Wistar rats were divided into ischemia, ischemia+NAC and control groups, and in
      the former 2 groups, acute myocardial ischemia models were produced by pituitrin.
      Elevated ST segment in ECG served as the indicator for myocardial ischemia. Rats
      in ischemia+NAC group were pre-treated with NAC (0.1 g/kg x d) for three weeks
      before the ischemia 8-iso-PGF2alpha levels in the plasma and myocardial tissue
      were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In
      ischemia group, the 8-iso-PGF2alpha levels in the plasma and myocardial tissue
      were 187.4+/-45.8 pg/ml and 259.3+/-47.5 pg/g, respectively, higher than those in
      the control group (60.4+/-13.7 pg/ml and 88.6+/-16.9 pg/g, respectively, P<0.01)
      and those in ischemia+NAC group (88.2+/-16.4 pg/ml and 109.4+/-24.7 pg/g,
      respectively, P<0.01). A positive correlation was noted between the 8-iso
      PGF2alpha levels in the plasma and myocardial tissue (r=0.865, P<0.01). In
      comparison with the control group, elevation of the ST segment of ECG in rats
      with myocardial ischemia was obvious, and the peak elevation occurred 45 min
      after ischemia (0.34+/-0.05 mV, P<0.01). Pre-treatment with NAC proved to help
      alleviate the subsequent ischemia, with ST segment elevation of only 0.18+/-0.05
      mV. CONCLUSION: In condition of acute myocardial ischemia in rats, 8-iso
      PGF2alpha levels tend to increase, which can be indicative of the degree of
      myocardial ischemia. NAC pre-treatment can alleviate the ischemic condition by
      offsetting the damage caused by the free radicals.

PMID- 12810390
TI  - [Effect of triglycerides on rat islet cell function in vitro].
AB  - OBJECTIVE: To study the effect of triglycerides (TGs) on the function of in vitro
      cultured rat islet cells. METHODS: SD rat islet cells were isolated for monolayer
      cell culture and treated with TGs at different concentrations (0, 0.5, 2.5, 5.0,
      10.0 mmol/L) for 72 h. Insulin level in the cell culture media was measured after
      glucose loading test, and the deposition of fat droplets in the islet cells
      observed by oil red O-staining. RESULTS: No obvious effect was observed after a
      72-h incubation of the islet cells with TGs at low glucose level (2.8 mmol/L),
      while with the stimulation of high-level glucose (27.8 mmol/L), the insulin
      secretion was significantly inhibited by TGs of higher concentrations (5.0, 10.0
      mmol/L). The deposition of fat droplets was found in the islet cells after
      incubation with TGs, with TGs of higher concentrations. CONCLUSION: TGs induces
      deposition of fat droplets in islet cells in vitro, and may inhibit the insulin
      secreting function of the cells.

PMID- 12810391
TI  - [Effects of basic fibroblast growth factor on rat models of Alzheimer disease].
AB  - OBJECTIVE: To study the effects of basic fibroblast growth factor (bFGF) on the
      praxiology and cerebral acetylcholinesterase (AchE) fiber density of kainic acid
      lesioned rat models of Alzheimer disease (AD). METHODS: AD models were induced in
      30 normal adult rats by damaging the rat nucleus basalis of Meynert (NBM) with
      kainic acid, and the models were then assigned into 3 groups to receive
      cerebroventricular infusion with bFGF, saline or nothing for treatment, serving
      respectively as the treatment group at 30 min, 1, 3 and 7 d after the injury,
      sham treatment group or injury group. Another 10 rats were used as control group,
      which received saline injections into the NBM without further treatment. The
      learning and memory abilities of the rats were measured through Y-maze test 30 d
      after the operations, and AchE cytochemical study was conducted to calculate the
      density of the AchE fibers in the hippocampus and forebrain of the rats. RESULTS:
      In comparison with the injury group, improvement was noted in the memory ability
      of rats with bFGF treatment and the density of AchE fiber was also significantly
      increased (P<0.01), but the improvement in both respects failed to reach the
      normal level (P<0.01). CONCLUSIONS: AD model can be successfully established by
      damaging the NBM with kainic acid, and bFGF is beneficial in improving the
      impaired learning and memory abilities and increasing the density of AchE fibers
      in the basal forebrain cortex and hippocampus in the models.

PMID- 12810392
TI  - [Establishment of rat models of simultaneous liver and kidney transplantation].
AB  - OBJECTIVE: To establish a simple and reliable rat model of simultaneous liver and
      kidney transplantation. METHODS: The simultaneous transplantation was performed
      in healthy male SD rats as the recipients and other SD rats of either gender as
      the donors. The donor liver and kidney were resected simultaneously and grafted
      into the recipients whose corresponding organs were previously removed.
      Anastomosis of the portal vein and the inferior vein cava (IVC) inferior to the
      kidney between the graft and the recipient was performed by a double cuff method,
      followed by end-to-side anastomosis of the IVC superior to the liver between the
      donor and the recipient. The urethra and bile duct were anastomised using a
      simple inside bracket. RESULTS: The time for blood vessel anastomosis and for
      recipient operation were reduced, with a success rate of 73.3% in the operations.
      The function of the grafted liver and kidney remained normal. CONCLUSION: This
      rat model of simultaneous liver-kidney transplantation is simple and reliable.

PMID- 12810393
TI  - [Hematopoietic reconstitution in early period after autologous and allogeneic
      peripheral blood stem cell transplantation].
AB  - OBJECTIVE: To investigate the ratio and amount of CD34+ cells and their subsets
      in mobilized peripheral blood (MPB) and leukapheresis products in patients
      receiving autologous peripheral blood stem cell transplantation (auto-PBSCT) and
      in allo-PBSCT donors, and clarify the role of CD34+ cells in post-transplantation
      hematopoietic reconstitution. METHOD: Sixteen patients receiving auto-PBSCT and
      24 allo-PBSCT donors were studied for CD34+ and CD34+CD38- cell ratios in the 115
      MPB and their leukapheresis product samples by way of flow cytometry, and the
      time of hematopoietic recovery was observed in the two groups. RESULTS: The CD34+
      cell ratio in the MPB samples and leukapheresis products was significantly lower
      in the donors than in auto-PBSCT patients (P<0.05), but CD34+CD38- cell ratio
      showed no obvious difference between the two groups. The amount of mononuclear
      cells (MNCs) received by allo-PBSCT patients was much more than that received by
      auto-PBSCT patients (P<0.01). Similar average times for post-transplant
      neutrophils recovery to over 0.5x10(9)/L and platelets to over 2 x 10(10)/L
      (P>0.05) were observed between the groups, and in both of them, the recovery was
      related to the amount of MNCs, CD34+ and CD34+/CD38- cell infusion. CONCLUSION:
      Irrespective of auto-PBSCT or allo-PBSCT, the number of CD34+ and CD34+CD38-cells
      infused after the transplantation is the key factor to influence the course of
      hemopoietic reconstitution.

PMID- 12810394
TI  - [Phenotype analysis of alpha1-antichymotrypsin in the Guangzhou Han population].
AB  - OBJECTIVE: To understand the phenotype distribution profile of alpha1
      antichymotrypsin (alpha1-ACT) in the Han population in Guangzhou municipality so
      as to decide whether geographical factors affect the distribution of alpha1-ACT
      phenotypes. METHODS: Polyacrylamide gel isoelectric focusing followed by
      immunofixation techniques was employed for examining the alpha1-ACT phenotypes in
      200 unrelated individuals randomly selected from the Guangzhou Han residents.
      RESULTS: Three phenotypes of alpha1-ACT were identified in this subject cohort,
      which were identical to those identified in Chongqing but with different
      distributions of the phenotype frequencies. CONCLUSION: Geographical factors may
      affect the distribution of the phenotype frequencies of alpha1-ACT, which is a
      promising genetic marker for the pursuit of human genetics.

PMID- 12810395
TI  - [Comparison of digital radiography and conventional X-ray in the diagnosis of
      solitary pulmonary nodule with receiver operating characteristic analysis].
AB  - OBJECTIVE: To compare digital radiographs with conventional radiographs in the
      detection of solitary pulmonary nodules. METHODS: Thirty patients with solitary
      pulmonary nodule and 30 cases without pulmonary nodules were enrolled in the
      study. The existence of solitary pulmonary nodule was confirmed by chest computed
      tomography (CT) as well as biopsy. All patients examined by both digital
      radiography (group A) and conventional radiographs (group B) were reviewed by
      four experienced chest radiologists and four residents. Assessment was performed
      with receiver operating characteristic (ROC) analysis of the images in both
      groups. RESULTS: (1) Observer performance of the experienced radiologists in
      group B (Az=0.838) was superior to that in group A (Az=0.816) (P<0.05) in
      detection of solitary pulmonary nodule. For the residents, observer performance
      in group B (Az=0.842) was superior to that in group A (Az=0.712) (P<0.05). (2)
      There was no difference between the two groups (P=0.272), for the judgement of
      benign or malignant solitary pulmonary nodule. CONCLUSIONS: Digital radiographs
      is superior to conventional radiographs in detection of solitary pulmonary
      nodule. However, there was no significant differences in discrimination between
      benign and malignant solitary pulmonary nodules in the two groups.

PMID- 12810396
TI  - [Causes of transplant renal arterial stenosis in cadaveric renal transplant
      recipients].
AB  - OBJECTIVE: To explore the possible causes of transplant renal artery stenosis
      (TRAS) in cadaveric transplant recipients. METHOD: We retrospectively analyzed
      multiple factors that may contribute to TRAS (including the patients' age,
      presence of diabetes, cold ischemic time, acute rejection episode,
      cytomegalovirus infection, serum cholesterol, LDL cholesterol, pre-operative
      dialysis, number of donor renal arteries, which side of donor kidney, type of
      surgical anastomosis, different protocols of inductive and maintenance drug
      therapy) in 18 recipients with transplant renal artery stenosis after cadveric
      renal transplantation from Jan. 2000 to Dec. 2001 in comparison with another 566
      non-TRAS recipients who underwent the transplantation during the same period.
      RESULTS: There was a higher incidence of acute rejection in the TRAS group than
      non-TRAS group (66.67% vs 5.48%, P<0.01), and no significant difference was noted
      between TRAS and non-TRAS cases in terms of the pre-operative dialysis, presence
      of diabetes, cold ischemic time, number of donor renal arteries, whith side of
      donor kidney, type of surgical anastomosis, different protocols of inductive and
      maintenance drug therapy, cytomegalovirus infections and serum and LDL
      cholesterols. CONCLUSION: The occurrence of TRAS in cadaveric allografts is
      associated with acute graft rejection episode, suggesting the importance of the
      treatment of acute graft rejection in the prevention of TRAS.

PMID- 12810397
TI  - [Psychological health status of students taking part in medical support for
      military training on the sea].
AB  - OBJECTIVE: To investigate the adaptability and psychological health status of the
      students from the military medical universities enrolled in the medical support
      service for military training on the sea, so as to provide more pertinent and
      specific psychological advice for students in military medical universities.
      METHODS: The psychological health status of 139 students were assessed by issuing
      a self-rating symptom scale (SCL-90) before the training and later before the
      maneuvers commenced, respectively. RESULTS: Except for obsessive-compulsive and
      interpersonal sensitivity factors, significant increases were recorded in the
      scores for other factors immediately before the maneuvers as compared with those
      recorded before the training (P<0.01, P<0.05). The positive symptom rates of
      various factors measured before the maneuvers were also higher. CONCLUSIONS: It
      is the essential task for daily psychological health education to help the
      students foster psychological self-regulation ability and cope with stresses to
      strengthen their psychological well-being. Building self-confidence, improving
      the adaptability and conquering fears should be the primary concern of the
      psychological advisors before military actions.

PMID- 12810398
TI  - [Traumatic nasal cerebrospinal fluid fistula: report of 86 cases].
AB  - The clinical record of 86 cases of traumatic nasal cerebrospinal fluid (CSF)
      fistula treated either surgically or conservatively between 1997 and 2001 was
      retrieved and analyzed. The fistula completely healed in 15 surgically treated
      patients (17.4%) and 71 conservatively treated patients (82.6%), and in the
      follow-up observation, recurrence was identified in none of the cases. Our
      experience approves the importance of head position, lowering intracranial
      pressure and application of antibiotics in the conservative therapy, and for
      surgical treatment, water-tight closure of the dura fistula should be performed.

PMID- 12810399
TI  - [Catheter-directed thrombolysis for iliofemoral vein thrombosis: report of 13
      cases].
AB  - OBJECTIVE: To evaluate the safety and effectiveness of catheter-directed
      thrombolysis in the treatment of iliofemoral vein thrombosis. METHODS: Thirteen
      cases of iliofemoral vein thrombosis were treated by urokinase administered in
      the forms of large bolus doses, medium-dose intra-catheter infusion and small
      dose intervenous injection in succession. The average time of intra-catheter drug
      administration was 18 h, with the average dose of urokinase of 3.31x10(6) U.
      RESULTS: Partial recanalization was achieved in all the cases and the rate for
      complete recanalization reached 84.6%. The clinical symptoms of the patients were
      significantly improved after treatment without serious complications. CONCLUSION:
      Catheter-directed thrombolysis is safe and effective for treating iliofemoral
      vein thrombosis.

PMID- 12810400
TI  - [Anatomic observation of the prostate for clinical application of local drug
      injection through the rectum for chronic prostatitis].
AB  - OBJECTIVE: To provide anatomic evidences for local drug injection through the
      rectum for treating chronic prostatitis and observe the therapeutic effect of
      this treatment. METHODS: Anatomic observation of the median sagittal plane of 16
      male pelvic specimens was conducted, with special attention to the structures
      between the prostate and the rectum. The distance from the posterior wall of the
      prostate to the anterior wall of the rectum, the scope that allowed the entry of
      the puncture needle, the appropriate puncture depth, and the distance from the
      anus to the safe were carefully measured. Analysis of the clinical record was
      performed in 51 chronic prostatitis cases treated with local injection of
      prednisolone, antibiotic and lidocaine through the rectum. RESULTS: Only some fat
      tissues and venous plexus were found between the prostate and the anterior wall
      of the rectum, and the distance from posterior wall of the prostate to the
      anterior wall of the rectum averaged 5.773+/-0.710 mm. The scope for possible
      puncture was 15.408 8+/-1.438 2 mm with a depth of 15.703 1+/-0.944 1 mm. The
      maximum and minimum distances from the anus to the puncture were 47.594+/-2.432
      mm and 35.781+/-1.850 mm, respectively. Among the 51 cases investigated, the
      total cure rate was 84.31%, and improvement was achieved in 13.73% of the case,
      with only one case (2%) failed to respond to the treatment. CONCLUSION: Local
      drug injection through the rectum can be ideal for the treatment of prostatitis
      for its safety and effectiveness.

PMID- 12810401
TI  - [Mixed infection of Strongyloides stercoralis and Clonorchis sinensis: report of
      one case].
AB  - OBJECTIVE: We report a case of mixed infection of Strongyloides stercoralis and
      Clonorchis sinensis, the diagnosis of which was difficult due to lack of specific
      clinical and imaging features. Definitive diagnosis was finally reached on the
      basis of detection of the larvae and eggs in the stool of the patient. Timely and
      effective therapy is of much importance for the prognosis of the disease.

PMID- 12810402
TI  - Captain Cook's beer: the antiscorbutic use of malt and beer in late 18th century
      sea voyages.
AB  - The custom of allowing British seamen the regular use of fermented liquor is an
      old one. Ale was a standard article of the sea ration as early as the fourteenth
      century. By the late eighteenth century, beer was considered to be at once a food
      (a staple beverage and essential part of the sea diet), a luxury (helping to
      ameliorate the hardship and irregularity of sea life) and a medicine (conducive
      to health at sea). In particular, beer and its precursors, wort and malt, were
      administered with the aim of preventing and curing scurvy. This paper examines
      the use of malt and beer during late eighteenth century British sea voyages,
      particularly their use as antiscorbutic agents, focusing on James Cook's three
      voyages during the period 1768-1780. Cook administered sweet wort (an infusion of
      malt), beer (prepared from an experimental, concentrated malt extract), and
      spruce beer (prepared mainly from molasses), among many other items, in his
      attempts to prevent and to cure scurvy. Despite the inconclusive nature of his
      own experiments, he reported favourably after his second voyage (1772-1775) on
      the use of wort as an antiscorbutic sea medicine (for which purpose it is now
      known to be useless). Cook thereby lent credibility to erroneous medical theories
      about scurvy, helping to perpetuate the use of ineffective treatments and to
      delay the discovery of a cure for the disorder.

PMID- 12810403
TI  - Nutrition and related claims used on packaged Australian foods--implications for
      regulation.
AB  - The aim of this study was to describe the use of nutrition and related claims on
      packaged food for sale in Australia and measure the compliance of such claims
      with regulations governing their use. A survey was conducted of the labelling of
      6662 products in 40 different food categories on sale in New South Wales in 2001.
      Levels of compliance were assessed by comparing the claims on the label and data
      in the nutrition information panel with requirements of the Foods Standards Code
      and the Code of Practice on Nutrient Claims. Half of the products (51.3%) carried
      some type of nutrition related claim and 36.2% made at least one nutrient claim,
      with an average of 1.2 nutrition related claims on every food product. The foods
      with the highest use of nutrient claims were sports drinks, breakfast cereals,
      meat substitutes, pretzels and rice cakes, muesli bars and yoghurt. The most
      common nutrient claims were for fat, cholesterol, vitamins, minerals, and sugar.
      More than 20% of products carried claims related to additives. Many nutrient
      claims (12.9%) did not comply with current regulations, especially those in the
      voluntary Code of Practice. Adoption of mandatory requirements for all claims
      within the Food Standards Code may improve the levels of compliance. Implications
      for the regulation of nutrition and related claims are discussed. The impact of
      nutrition claims on consumer purchasing and consumption behaviour deserves
      further study.

PMID- 12810404
TI  - Effect of dietary medium- and long-chain triacylglycerols (MLCT) on accumulation
      of body fat in healthy humans.
AB  - We investigated whether a structured medium- and long-chain triacylglycerols
      (MLCT) diet could decrease accumulation of body fat in healthy humans. The study
      was conducted under a double-blind randomized design. Ninety-three subjects
      participated in this study. However, 10 subjects could not consume the specified
      meal, and one subject wished to opt out. Consequently, the study included 82
      subjects. The experimental subjects consumed the test bread, which was made with
      14 g of MLCT containing 1.7 g MCFA, daily at breakfast during the study period of
      12 weeks, and the control subjects consumed bread made with long-chain
      triacylglycerols (LCT). All subjects consumed the same standard packaged meals.
      Body composition parameters were body weight, total body fat and abdominal fat,
      and blood analyses included serum cholesterol, triacylglycerols and
      phospholipids. Significant decreases of body weight, the amount of body fat,
      subcutaneous and visceral fat were noted in the MLCT group as compared with those
      of the LCT group for 12 weeks (P<0.05). Furthermore, a significant decrease in
      serum total cholesterol was noted in the MLCT group as compared with that of the
      LCT group at 8 weeks (P<0.05). However, other serum parameters were not different
      between the MLCT and LCT groups. The results suggest that the daily intake of
      MLCT diet could result in a reduction in body weight and in accumulation of body
      fat, and, moreover, it could reduce serum total cholesterol.

PMID- 12810405
TI  - Assessment of bioelectrical impedance analysis for the prediction of total body
      water in cystic fibrosis.
AB  - The aim of this study was to compare the measurement of total body water (TBW) by
      deuterium (2H2O) dilution and bioelectrical impedance analysis (BIA) in patients
      with cystic fibrosis (CF) and healthy controls. Thirty-six clinically stable
      patients with CF (age 25.4+/-5.6 yrs) and 42 healthy controls (age 25.4+/-4.8)
      were recruited into this study. TBW was measured by 2H2O dilution and predicted
      by BIA in patients and controls. The TBW predicted from BIA was significantly
      different from TBW as measured using 2H2O in patients (P<0.05) but not in
      controls. Mean (+/-SD) values for predicted and measured TBW differed by 5.6 (+/
      9.1) L in patients and 0.4 (+/-3.6)L in controls. This bias was consistent for
      all controls but not for patients. In CF, BIA over predicted TBW determined by
      2H2O dilution to an increasing extent at larger TBW volumes. There was a strong
      correlation between height2/impedance and TBW in patients with CF (r=0.90;
      y=0.67x+2.50) and in controls (r=0.81; y=0.57x+9.60). The slope of the regression
      lines was similar for both groups, however the y intercepts were significantly
      different (P<0.05). BIA overestimates TBW in patients with CF, possibly due to
      invalid factory installed regression equations within BIA instrumentation. Future
      studies employing BIA as a measure of TBW or FFM in CF should use alternative
      predictive equations to those that have been developed for healthy individuals. A
      large scale study to develop specific regression equations for use in CF is
      warranted.

PMID- 12810406
TI  - Association of food patterns, central obesity measures and metabolic risk factors
      for coronary heart disease (CHD) in middle aged Bengalee Hindu men, Calcutta,
      India.
AB  - The association of central obesity measures and food patterns with metabolic risk
      factors for coronary heart disease (CHD) were studied among middle aged (>or =30
      years) Bengalee Hindu men of Calcutta, India. CHD risk factors included total
      cholesterol (TC), fasting triglyceride (FTG), fasting plasma glucose (FPG), high
      density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL
      c) and very low density lipoprotein cholesterol (VLDL-c). The total sample size
      in the study was 212 male individuals. Anthropometric measurements, metabolic and
      food pattern variables were collected from each participant. The relative role of
      central obesity measures and food pattern variables in explaining metabolic risk
      factors of CHD were also made in this study. The results revealed that body mass
      index (BMI) had no significant relation with any of the metabolic risk factors of
      CHD. Whereas almost all-central obesity measures, namely waist circumference
      (WC), waist-hip ratio (WHR), and conicity index (CI) were significantly and
      positively related with TC, FTG, FPG and VLDL-c. Of the food pattern variables,
      only the frequency of egg, fried snacks and Bengalee sweets consumption were
      positively and significantly related with all central obesity measures. In
      contrast, frequency of chicken and fish consumption was negatively associated
      with central obesity measures. Conicity index (CI) was found to be the most
      consistent in explaining metabolic variables of CHD. Percent of variance
      explained by central obesity measures and food patterns were TC (10%), FPG (16%),
      FTG (6.6%) and VLDL-c (6.7%). Significant negative association of chicken and
      fish consumption with central obesity measures indicates the beneficial effect of
      both these items in this population.

PMID- 12810407
TI  - Energy, protein, calcium, vitamin D and fibre intakes from meals in residential
      care establishments in Australia.
AB  - Residents from high level (nursing homes) and low-level care facilities (hostel)
      being served the three common diet texture modifications (full diet, soft-minced
      diet and pureed diet) were assessed. Individual plate waste was estimated at
      three meals on one day. Fifty-six males and 156 females, mean age 82.9+/-9.5 (SD)
      years, of which 139 lived in nursing homes (NH) and 76 in hostels (H) were
      included. Mean total energy served from meals was 5.3 MJ/day, 5.1 to 5.6 MJ/day,
      95% confidence intervals (CI), in NH which was less than in H, 5.9 MJ/day (CI 5.6
      to 6.2 MJ/day) (P=0.007). Protein and calcium intakes were lower in NH, 44.5g (CI
      41.5 to 47.5g), 359.0mg (CI 333.2 to 384.8mg), versus 50.5g (CI 46.6 to 54.3g),
      480.5mg (CI 444.3 to 516.7mg) in H (P=0.017, P<0.001 respectively). There was no
      difference in nutrient/energy ratios, except for protein/energy, which was higher
      in NH 11.7 (CI 11.3 to 12.2) than in H 9.8 (CI 9.4 to 10.3) (P<0.001). Ability to
      self-feed had no significant effect on nutrient intakes in NH. The self fed group
      (N=63) had the following nutrient intakes: energy 4.0 MJ (CI 3.6 to 4.3 MJ),
      protein 44.6g (CI 40.3 to 48.9g), calcium 356.9mg (CI 316.3 to 397.4mg), fibre
      14.9g (CI 13.2 to 16.5g). The assisted group (N=64) had the following nutrient
      intakes: energy 3.9MJ (CI 3.6 to 4.2MJ), protein 46.0g (CI 40.7 to 49.6), calcium
      361.9mg (CI 327.8 to 396.1mg), fibre 14.9g (CI 13.2 to 16.1g). Of NH classified
      as eating impaired, 36% received no assistance with feeding and had lower intakes
      of protein 37.8g (CI 33.0 to 42.1g) compared to those receiving some assistance
      46.1g (CI 41.3 to 50.9g) (P=0.026). Reduced energy intake accounted for the
      differences in nutrient intakes between nursing homes and hostels, except for
      protein. Strategies to effectively monitor nutrient intakes and to identify those
      with eating impairment are required in order to ensure adequate nutrition of
      residents in nursing homes and hostels.

PMID- 12810408
TI  - Micronutrient status of primary school girls in rural and urban areas of South
      Vietnam.
AB  - Dietary habits, especially micronutrient intake, and nutritional status of
      Vietnamese primary school girls were investigated in a cross-sectional survey. We
      interviewed 284 girls aged 7 to 9 years old, randomly selected from three rural
      (N=148) and two urban (N=136) primary schools. Dietary data were calculated from
      the results of 24-h recall interviews over three consecutive days. The dietary
      micronutrient pattern of the rural group showed deficiency of iron, calcium,
      phosphorus, potassium, magnesium, beta-carotene, vitamin A and vitamin C. On the
      contrary, adequate consumption of these elements, except low beta-carotene, was
      observed in the urban group. Despite a low prevalence of anaemia, the prevalence
      of rural children with iron deficiency was close to the level regarded as being a
      public health problem. In contrast, 7.7% of urban children were found to have
      excessive iron status. Children with exhausted retinol stores (7.1%) requiring
      immediate retinol supplementation were only found in the rural group.
      Furthermore, the prevalence of children with marginal retinol stores in both the
      rural (35.7%) and urban (21.4%) groups was above the level of being a public
      health problem (20%). In both groups, more than 50% and 20% of children showed
      beta-carotene and tocopherol levels in the range of severe deficiency,
      respectively. Thus, nutritional education to improve the dietary habits of the
      two groups is necessary for Vietnamese primary school children.

PMID- 12810409
TI  - Academic performance of Korean children is associated with dietary behaviours and
      physical status.
AB  - The purpose of this study was to obtain a fuller understanding of the association
      of dietary behaviours, physical status and socio-economic status with academic
      performance in Korean teenagers. The subjects in this study were 6,463 boys and
      girls, in grade 5, 8, and 11 in Korea. A self-administered questionnaire and the
      food-frequency form were used. Grade point average (GPA), height, weight, and
      physical fitness score for the year were recorded from the school record. The
      academic performance of students was strongly associated with dietary behaviours,
      especially with regularity of three meals even after control for parent's
      education level. Regular breakfast and lunch were more important in grades 5 and
      8, while regular dinner was more related with academic performance in grade 11.
      Small, positive associations of height and physical fitness to academic
      performance were also found. The relative importance of regularity of meals was
      greater than that of socio-economic status and physical status in older
      teenagers. The results of this study suggest that accommodation of better dietary
      environment and nutrition education for three regular meals is recommended.

PMID- 12810410
TI  - Effect of carob bean on gastric emptying time in Thai infants.
AB  - Thickening agents, such as carob bean gum or galactomannan, have been
      successfully administered for the treatment of gastroesophageal reflux in
      infants. To study the effect of carob bean gum on gastric emptying and to
      symptoms of regurgitation, we recruited 20 full term Thai infants (mean
      age=13.4+/-7 week; mean body weight=4943+/-1272gm) without pathological
      gastroesophageal reflux. Initially, we determined half time gastric emptying (T
      1/2 GET) by Tc99m radioscintigraphy method (mean T 1/2 GET=116.1+/-72 min) in
      infants consuming standard infant cow's milk formula for 2 weeks. Afterwards,
      carob bean infant formula was given for 2-4 weeks and weight gain, vomiting
      symptoms, night cough, colic, flatus, defaecation character and T 1/2 GET were
      assessed. There were statistically significant improvements in symptoms of
      vomiting (a smaller quantity P<0.001 and frequency of vomiting P<0.0001) and
      improvements in weight gain per week (W1=121.2+106.9gm, W2=221.3+136.1gm;
      P=0.005) when infants consumed the carob bean formula. However, there was no
      significance difference in gastric emptying half time (GET1=116.1+72,
      GET2=148.5+130.9; P=0.154). In conclusion, carob bean gum, as a thickening agent,
      improves the clinical symptoms of regurgitating infants, but does not
      significantly alter the gastric emptying physiology.

PMID- 12810411
TI  - Iron deficiency anaemia in childhood and thyroid function.
AB  - Studies in animals and adults have indicated iron deficiency anaemia to be
      associated with altered thyroid hormone metabolism. The aim of the present study
      was to determine the effect of iron deficiency anaemia on the thyroid function of
      young children. Concentrations of thyroxine (T4) and triiodothyronine (T3), free
      thyroid hormones (fT4 and fT3), thyroxine binding globulin (TBG), and thyroid
      stimulating hormone (TSH) were measured in the basal state and in response to an
      intravenous bolus of thyrotropin releasing hormone (TRH) in nine children one to
      three years of age with iron deficiency anaemia (IDA) before and after treatment
      with oral iron. The results of the anaemic children were also compared to basal
      and stimulated concentrations of thyroid hormones, TBG, and TSH of eight iron
      sufficient, age-matched children. Seven of the IDA and 6 of the control children
      were male. The mean haemoglobin (Hb) and serum ferritin (SF) in the IDA children
      at baseline were 93g/L (range 81-102) and 6g/L (range 1-12) which increased to
      121g/L (range 114-129) and 54g/L (range 19-175), respectively, after a mean of
      2.3 months (SD 0.5) of iron therapy. In the control group, mean Hb and SF were
      125g/L (range 114-130) and 51 g/L (range 24-144), respectively. The basal values
      of TBG and thyroid hormones of the IDA children before and after iron treatment
      were not different from the control children. Similarly, there was no statistical
      difference in the thyroid hormones in the IDA children before compared to after
      resolution of the anaemia. Compared to the control children, the TSH response
      over time to TRH, TSH area under the curve (TSHAUC), and the peak TSH value after
      stimulation were all lower in the IDA children both before and after resolution
      of anaemia, but the differences were not significant. Iron therapy and resolution
      of anaemia had no effect among the IDA children. The time to reach the peak TSH
      concentration was longer in the IDA children (P=0.08) than the control children
      before iron therapy. While the time to peak TSH decreased upon resolution of the
      anaemia, the difference was not significant. There was no effect of Hb
      concentration, age, or anthropometry with TSH, TSHAUC, or time to peak TSH after
      TRH stimulation in the IDA children before treatment. Normal thyroid function was
      preserved in these children with iron deficiency anaemia, however three of nine
      children had minor abnormalities of hypothalamic-pituitary function. These
      results indicate that hypothyroidism is unlikely to be a major cause of impaired
      psychomotor development or growth in young children with iron deficiency anaemia.

PMID- 12810412
TI  - Nutritional status of Korean male patients with alcoholic and viral liver
      cirrhosis.
AB  - This descriptive cross-sectional study aimed to investigate whether malnutrition
      occurs in outpatients with liver cirrhosis, and to compare the nutritional status
      of patients with alcoholic and viral liver cirrhosis using a variety of objective
      measures. This study also aimed to provide useful information about nutritional
      education and nutritional therapies for medical teams and patients with liver
      cirrhosis. Sixty-six Korean men between the ages of 30 and 69 with liver
      cirrhosis (24 alcohol-related and 42 virus-related) were recruited from the
      Internal Medicine Centres, Hanyang University Hospital, Seoul, Korea. The results
      showed that patients with alcoholic liver cirrhosis (ALC) were significantly
      lower in socio-economic status than patients with viral liver cirrhosis (VLC)
      (P<0.05). The energy intakes (excluding alcohol-derived energy) were 1448kcal and
      1769kcal in the ALC and the VLC groups, respectively (P<0.05). As well, vitamin C
      intake was found to be higher in the VLC group than the ALC group, yet still more
      than 125% of the RDA for both groups (P<0.05). Among nutritional indices, only
      the TSF thickness showed interaction with the aetiology and the severity of the
      cirrhosis (P<0.05). Thus, these findings indicate that outpatients with liver
      cirrhosis in this study, particularly those with alcoholic liver cirrhosis,
      consumed a lower energy intake than suggested, but may not have been in a status
      of malnutrition. Body fat is more affected than other nutritional parameters in
      patients with liver cirrhosis.

PMID- 12810413
TI  - Blood cholesterol and lipid-lowering effects of carrageenan on human volunteers.
AB  - Algal polysaccharides such as carrageenan are good sources of dietary fibre.
      Previous studies have shown that carrageenan has hypoglycemic effects, but its
      cholesterol and lipid-lowering effects have yet to be demonstrated. In this
      study, carrageenan was incorporated into 4 food items, then fed to 20 human
      volunteers to determine its effects on blood cholesterol and lipid levels. The
      study followed a randomized crossover design. Each phase of the study--control
      and experimental--lasted for 8 weeks separated by a 2-week washout. At control,
      the subjects consumed their usual food intake; at experimental, they were given
      test foods with carrageenan partly substituting similar items in their usual
      diet. Fasting venous blood samples were collected immediately before and after
      each phase to assay serum cholesterol and triglyceride. The mean serum
      cholesterol was significantly lower (P<0.0014) after the experimental phase at
      3.64 mmol/L compared with the mean level after the control phase, 5.44 mmol/L.
      The mean triglyceride level after the experimental phase, 0.87 mmol/L, was
      significantly lower (P<0.0006) in comparison to the level after the control
      phase, 1.28 mmol/L. The mean HDL cholesterol level significantly increased
      (P<0.0071) after the experimental phase at 1.65 mmol/L compared to the mean value
      after the control phase, 1.25 mmol/L. No significant differences were observed
      between the LDL cholesterol levels after the experimental and the control phases.
      This study indicates that regular inclusion of carrageenan in the diet may result
      in reduced blood cholesterol and lipid levels in human subjects.

PMID- 12810414
TI  - Retinoic acid receptor-beta mRNA expression during chemoprevention of hamster
      cheek pouch carcinogenesis by garlic.
AB  - The effect of aqueous garlic (Allium sativum Linn.) on retinoic acid receptor
      beta (RARbeta) mRNA expression was investigated in male Syrian hamsters during 12
      dimethyl enz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis. RARbeta mRNA expression was analysed by slot blotted
      hybridization with radiolabelled RAR-beta probe. In DMBA-induced HBP tumours,
      decreased expression of RARbeta mRNA was observed. Administration of garlic
      (250mg/kg body weight) to animals painted with DMBA restored RARbeta mRNA
      expression to normal pattern suggesting that this may be one of the mechanisms by
      which garlic exerts its chemopreventive effects.

PMID- 12810415
TI  - Bioavailability of soluble oxalate from spinach eaten with and without milk
      products.
AB  - Leafy vegetables such as spinach (Spinacia oleracea) are known to contain
      moderate amounts of soluble and insoluble oxalates. Frozen commercially available
      spinach in New Zealand contains 736.6+/-20.4 mg/100g wet matter (WM) soluble
      oxalate and 220.1+/-96.5mg/100g WM insoluble oxalate. The frozen spinach
      contained 90mg total calcium/100g WM, 76.7%of this calcium was unavailable as it
      was bound to oxalate as insoluble oxalate. The oxalate/calcium (mEq) ratio of the
      frozen spinach was 4.73. When frozen convenience food is grilled there is no
      opportunity for the soluble oxalates to be leached out into the cooking water and
      discarded. Soluble oxalates, when consumed, have the ability to bind to calcium
      in the spinach and any calcium in foods consumed with the spinach, reducing the
      absorption of soluble oxalate. In this experiment 10 volunteers ingested 100g
      grilled spinach alone or with 100g additions of cottage cheese, sour cream and
      sour cream with Calci-Trim milk (180 g) and finally, with 20g olive oil. The
      availability of oxalate in the spinach was determined by measuring the oxalate
      output in the urine over a 6-hour and 24-hour period after intake of the test
      meal. The mean bioavailability of soluble oxalate in the grilled spinach was
      0.75+/-0.48% over a 6-hour period after intake and was 1.93+/-0.85% measured over
      a 24-hour period. Addition of sour cream and Calci-Trim milk reduced the
      availability of the oxalate in the spinach significantly (P<0.05) in both the 6
      hour and 24-hour collection periods.

PMID- 12810416
TI  - Metabolic effects of D-psicose in rats: studies on faecal and urinary excretion
      and caecal fermentation.
AB  - D-psicose (D -ribo-2-hexulose), a C-3 epimer of D-fructose, is one of the "rare
      sugars" present in small quantities in commercial carbohydrate complex or
      agricultural products. We investigated the absorption and excretion of D-psicose
      when orally administrated (5g/kg body weight) to Wistar rats, and the
      fermentation of D-psicose was measured as caecal short-chain fatty acids (SCFAs)
      when fed to rats in controlled diets (0, 10, 20 and 30%). Urinary and faecal
      excretions of D-psicose over the 24 h, following a single oral administration,
      were 11-15% of dosage for the former and 8-13% of dosage for the latter. Serum D
      psicose concentration and D-psicose in the contents of stomach and small
      intestines decreased progressively after administration. D-psicose in caecum
      contents was detected after 3h and 7h administration, but not after 1h. Rats fed
      on D-psicose diets showed short-chain fatty acid production with caecal
      hypertrophy. These results suggest that D-psicose is partly absorbable in the
      digestive tract and is excreted into urine and faeces. As with other poorly
      absorbed dietary carbohydrates, D-psicose is fermented in the caecum by
      intestinal microflora.

PMID- 12810417
TI  - Circadian rhythms in RA.

PMID- 12810419
TI  - Systemic vasculitis following an unreported rat bite.

PMID- 12810418
TI  - Interpreting radiographic data in rheumatoid arthritis.
AB  - Plain film radiography is the preferred method for evaluating disease progression
      in rheumatoid arthritis and for establishing the efficacy of new disease
      modifying antirheumatic agents. However, the relative efficacy of these agents
      cannot be determined by comparing radiographic data from different studies, and a
      standardised system is needed.

PMID- 12810420
TI  - Increased carotid artery intima-media thickness may be associated with stroke in
      primary antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate the prevalence and clinical significance of carotid
      artery intima-media thickness (IMT) in patients with primary antiphospholipid
      syndrome (APS). METHODS: 28 patients with primary APS with at least a five year
      follow up, and 28 healthy subjects, matched by age and sex, were included in the
      study. Colour Doppler with high resolution B mode carotid ultrasonography and
      spectral analysis were performed in patients and controls. Information on
      cardiovascular risk factors and the clinical course were collected. RESULTS: The
      mean (SD) age of patients and controls (12 male, 16 female in each group) was 40
      (8.5) years; the mean (SD) disease duration 7.7 (3) years. Carotid artery IMT was
      found in 23/28 patients (2.6 (1.14) mm) and 7/28 controls (1.2 (0.44))
      (p=0.0001). A decrease in the lumen diameter was also found in 11/28 patients
      with primary APS without carotid atherosclerotic plaque, and 2/28 controls
      (p=0.004). Hyperlipidaemia, diabetes, smoking, obesity, and hypertension were not
      associated with carotid artery IMT. Patients with carotid artery IMT had arterial
      vascular disease more often than patients without: 9/23 v 0/5 (p<0.009). These
      patients had stroke (seven patients), myocardial infarction (one), and mesenteric
      thrombosis (one). Subjects with IMT had a threefold higher risk for stroke than
      those without IMT (95% CI 0.78 to 14.3). CONCLUSIONS: Patients with primary APS
      have a high prevalence of carotid artery IMT and a decreased lumen diameter. IMT
      in primary APS may be associated with stroke. Patients with primary APS with IMT
      must be considered as carriers of atherosclerosis.

PMID- 12810421
TI  - Course of radiographic damage over 10 years in a cohort with early rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate development of radiographic damage in hands and feet of
      patients with early rheumatoid arthritis (RA) monitored prospectively for 10
      years, and to search for prognostic factors. PATIENTS AND METHODS: 181 patients
      with early RA (mean disease duration one year) were assessed annually with
      radiographs of hands and feet during years 0-5 and at year 10. Radiographs were
      evaluated according to Larsen (range 0-200). Predictive factors for progressive
      disease for years 0-5 and 5-10 were evaluated by logistic regression analyses.
      RESULTS: 82/168 (49%) patients had erosions at inclusion and almost all became
      erosive with time (90% after two years and 96% after 10 years). Radiographic
      progression was most rapid during the first two years and 75% of all damage
      occurred during the first five years. The median Larsen score increased from 6 at
      inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all
      evaluated joints became maximally eroded, the second metacarpophalangeal joint
      being the most commonly affected. Mean ESR during the first three months and
      rheumatoid factor status were significant predictors for radiographic progressive
      disease, it was not possible to predict non-progressive disease. CONCLUSIONS:
      Joint damage in hands and feet developed early and progression was most rapid
      during the first years of disease. The different rates of progression at
      different stages should be considered in the design of trials of drugs aimed at
      retarding joint damage. Disease activity at study start influenced the degree of
      joint damage during the entire 10 years.

PMID- 12810422
TI  - Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly
      associated with generalised osteoporosis.
AB  - OBJECTIVES: To investigate determinants of joint destruction and reduced bone
      mineral density (BMD) in postmenopausal women with active rheumatoid arthritis
      (RA) not treated with bisphosphonates or hormone replacement therapy and to
      evaluate if there are common markers of erosive disease and bone loss. METHODS:
      BMD was measured using dual x ray absorptiometry and joint damage was examined by
      x ray examination according to the Larsen method in 88 patients with RA.
      Associations between BMD and Larsen score, and between demographic and disease
      related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and
      markers of bone and cartilage turnover, were examined bivariately by simple and
      multiple linear regression analyses. RESULTS: 49/88 (56%) patients had
      osteoporosis in at least one site. Reduced BMD and increased joint destruction
      were associated with: at the forearm and femoral neck, high Larsen score, low
      weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at
      the total hip, low weight, high Larsen score, and dose of injected
      glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight,
      reduced cartilage oligomeric matrix protein, and increased carboxyterminal
      propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was
      associated with long disease duration and increased C reactive protein (CRP)
      (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal
      patients with RA. Low weight and high Larsen score were strongly associated with
      BMD reduction. Increased CRP and long disease duration were determinants of
      erosive disease in postmenopausal women with RA. These findings indicate common
      mechanisms of local and generalised bone loss in RA.

PMID- 12810423
TI  - Effectiveness of a measurement feedback system on outcome in rheumatoid
      arthritis: a controlled clinical trial.
AB  - BACKGROUND: With the help of a measurement feedback system, the treatment
      strategy for individual patients with rheumatoid arthritis (RA) can be adjusted
      to achieve optimal control of disease activity. OBJECTIVE: To study whether a
      measurement feedback system is effective in reducing disease activity in patients
      with RA. METHODS: Forty eight rheumatologists and 264 patients participated in a
      controlled clinical trial. A three month control period was followed by a 12
      month period, where feedback on disease activity, disability, and damage was
      provided to the rheumatologist. The primary outcome measure was the rheumatoid
      arthritis disease activity index (RADAI). RESULTS: The feedback system was used
      for 142/228 (62%) patients. Disease modifying antirheumatic drug changes occurred
      in 69/169 (41%) patients. In patients with high disease activity and feedback use
      (n=70), the RADAI decreased in the feedback period by -0.27 points per 30 days
      (p<0.05), as compared with the control period. Patients for whom the feedback
      system was used had a better outcome than non-users. CONCLUSION: Much more
      training on the use of a feedback system and outcome measures, as well as the
      inclusion of explicit treatment guidelines will be necessary to increase the
      clinical use of measurement feedback and, possibly, to reduce disease activity
      for a larger number of patients with RA.

PMID- 12810424
TI  - Increased inflammatory activity parallels increased basal nitric oxide production
      and blunted response to nitric oxide in vivo in rheumatoid arthritis.
AB  - BACKGROUND: Endothelial dysfunction, defined as loss of bioactivity of NO in the
      vessel wall, is thought to precede atherosclerosis. OBJECTIVE: To determine
      whether endothelial dysfunction characterises patients with RA and whether these
      patients have increased inducible nitric oxide synthase (iNOS) dependent NO
      production in vivo. METHODS: and results: Twenty patients with RA and 33 normal
      subjects received intrabrachial artery infusions of endothelium dependent
      (acetylcholine (ACh)) and independent (sodium nitroprusside (SNP)) vasodilators
      to determine arterial responsiveness to NO. Basal flow and its percentage
      decrease by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of both iNOS and
      endothelium dependent NOS (eNOS), was used to determine the contribution of iNOS
      and eNOS dependent NO to basal flow. Both SNP (p<0.01) and ACh (p<0.05) increased
      blood flow significantly less in patients with RA than normal subjects. Serum
      concentrations of TNFalpha were, within the RA group, inversely correlated with
      blood flow responses to both SNP (r=-0.67, p=0.002) and ACh (r=-0.64, p<0.005).
      Basal flow was significantly increased in RA and correlated within this group
      with serum CRP (r=0.48, p<0.05), TNFalpha (r=0.61, p<0.01) concentrations, and
      ESR (r=0.68, p<0.002). L-NMMA decreased basal flow significantly more (-34+/-2%)
      in the patients with RA than the normal subjects (-24+/-3%, p<0.02), suggesting
      in view of the blunted response to ACh, increased iNOS activity. CONCLUSIONS:
      Patients with RA have a dual abnormality in NO dependent vascular function. Basal
      blood flow is increased in proportion to inflammatory activity and more inhibited
      by L-NMMA, suggesting increased iNOS activity, and responsiveness to NO is
      reduced.

PMID- 12810425
TI  - Analysis of the cell infiltrate and expression of proinflammatory cytokines and
      matrix metalloproteinases in arthroscopic synovial biopsies: comparison with
      synovial samples from patients with end stage, destructive rheumatoid arthritis.
AB  - BACKGROUND: Synovial tissue (ST) from end stage destructive rheumatoid arthritis
      (RA) and arthroscopic biopsies obtained during active inflammation might exhibit
      different characteristics. OBJECTIVE: To define the cell infiltrate and the
      expression of proinflammatory cytokines, angiogenic factors, and matrix
      metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from
      end stage RA. METHODS: Synovial biopsy specimens were obtained from the actively
      inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared
      with ST from 10 patients with end stage, destructive RA. Immunohistological
      analysis was performed to detect T cells, plasma cells, macrophages, fibroblast
      like synoviocytes (FLS), and the expression of interleukin (IL)1beta, IL6, tumour
      necrosis factor alpha (TNFalpha), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF.
      RESULTS: The expression of CD68+ macrophages was significantly higher in ST
      selected at arthroscopy than in samples obtained at surgery, both in the intimal
      lining layer and in the synovial sublining. The expression of CD3+ T cells also
      tended to be higher in arthroscopic samples. The expression of TNFalpha, IL6, MMP
      1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at
      arthroscopy. In contrast, the expression of IL1beta was on average higher in
      surgical samples. CONCLUSION: Active arthritis activity is associated with
      increased cell infiltration, expression of proinflammatory cytokines, MMPs, and
      angiogenic growth factors in synovial biopsy samples selected at arthroscopy.
      Increased expression of IL1beta in the synovium of patients with destructive RA
      requiring joint replacement may well reflect the important role of IL1beta in
      cartilage and bone destruction.

PMID- 12810426
TI  - Epidural corticosteroid injections for sciatica: a randomised, double blind,
      controlled clinical trial.
AB  - OBJECTIVE: To determine the efficacy of epidural corticosteroid injections for
      sciatica. METHODS: Three epidural injections (two day intervals) of 2 ml
      prednisolone acetate (50 mg) or 2 ml isotonic saline were administered to
      patients with sciatica presumably due to a disk herniation lasting 15-180 days.
      Self evaluation was the main judgment criterion at day 20. Patients who recovered
      or showed marked improvement were considered as success. Pain measured by VAS,
      the SLR test, Schober's test, Dallas pain questionnaire, and the Roland-Morris
      index were evaluated at days 0, 5, 20, and 35. Only analgesics were authorised,
      patients requiring non-steroidal anti-inflammatory drugs (NSAIDs) before day 20
      were considered as failure. RESULTS: 42 patients were included in the control
      group (CG), 43 in the steroid group (SG). On an intention to treat analysis 15/42
      (36%) in the CG and 22/43 (51%) in the SG (p=0.15) were considered as success
      (difference 15.5%, 95% CI (-5.4 to 36.3)). Among the 48 failures, 14 patients (6
      CG, 8 SG) required NSAIDs, 3 (2 CG, 1 SG) required surgery, and 7 (3 CG, 4 SG)
      other treatments. On analysis according to protocol, in 74 remaining patients
      12/35 (34%) in the CG and 22/39 (56%) in the SG (p=0.057) were considered as
      success (difference 22.1%, 95% CI (0.0 to 44.2)). For all secondary end points
      intragroup improvement with time was significant, but intergroup differences were
      not. CONCLUSION: The efficacy of isotonic saline administered epidurally for
      sciatica cannot be excluded, but epidural steroid injections provide no
      additional improvement.

PMID- 12810427
TI  - Prevalence of self reported musculoskeletal diseases is high.
AB  - OBJECTIVES: To present the prevalence of self reported musculoskeletal diseases,
      the coexistence of these diseases, the test-retest reliability with six months in
      between, and the association with musculoskeletal pain symptoms. METHODS: Twelve
      layman descriptions of common musculoskeletal diseases were part of the
      questionnaires of a prospective cohort study of a random sample in the general
      Dutch population aged 25 years or more (baseline: n=3664, follow up after six
      months: n=2338). Data collection also included information about pain relating to
      five different anatomical areas. RESULTS: Osteoarthritis of the knee (men 10.1%,
      women 13.6%) was amongst the most reported musculoskeletal diseases, whereas the
      figures for self reported rheumatoid arthritis (RA) were 1.6% and 4.6% for men
      and women, respectively. The coexistence of these diseases is high: 47 of the 66
      combinations were reported more often than would be expected if they were
      independent of each other (p<0.05). For most diseases the test-retest reliability
      was good (kappa between 0.6 and 0.8), but for repetitive strain injury
      (kappa=0.37) and chronic arthritis other than RA (kappa=0.44) the agreement was
      fair to moderate. All complaints of pain were more often reported by those with
      musculoskeletal diseases than those without those diseases, and the pain pattern
      was disease-specific. CONCLUSIONS: Self reported musculoskeletal diseases are
      highly prevalent, with a fair to good reliability and a disease-specific pain
      pattern. Health surveys are a limited but valuable source of information for this
      group of health problems, which is not available from most other sources of
      information.

PMID- 12810428
TI  - Correlations of Y chromosome microchimerism with disease activity in patients
      with SLE: analysis of preliminary data.
AB  - BACKGROUND: Recently it has been suggested that microchimerism may have a
      significant role in the aetiopathogenesis of some autoimmune diseases.
      OBJECTIVES: To evaluate the incidence of microchimerism in systemic lupus
      erythematosus (SLE), to quantify the phenomenon, to evaluate changes of
      microchimerism during follow up, and to correlate these data with clinical and
      laboratory variables. METHODS: Patients were selected for the study on the basis
      of the following criteria: (a) pregnancy with at least one male offspring; (b) no
      history of abortion and blood transfusion. Microchimerism was detected using a
      competitive nested polymerase chain reaction for a specific Y chromosome sequence
      and an internal competitor designed ad hoc. Disease activity and organ
      involvement were also evaluated. RESULTS: Sixty samples from 22 patients with SLE
      and 24 healthy controls were examined. Microchimerism was seen in 11 (50%)
      patients and 12 (50%) controls. The mean number of male equivalent cells was 2.4
      cells/100 000 (range 0.1-17) in patients with SLE and 2.5 (range 0.2-1.8) in
      healthy controls. No differences in the incidence of microchimerism or in the
      number of microchimeric cells were found between patients and healthy controls.
      Patients with a history of lupus nephritis had a higher mean number of fetal
      cells than patients with no such history. Disease activity did not appear to
      correlate with microchimerism. CONCLUSIONS: The preliminary data suggest that
      microchimerism does not interfere with the disease course of SLE, although
      further analysis on larger groups will be necessary to confirm these
      observations.

PMID- 12810429
TI  - Antibiotic treatment and long term prognosis of reactive arthritis.
AB  - OBJECTIVE: To evaluate whether a three month course of lymecycline has an effect
      on the long term prognosis of reactive arthritis (ReA). METHODS: In 1987-88 a
      double-blind controlled study with three month course of lymecycline/placebo was
      conducted. 17 of 23 patients treated at the outpatient department of Helsinki
      University Central Hospital volunteered to take part in a follow up study, where
      a physical examination were performed, and erythrocyte sedimentation rate, C
      reactive protein, rheumatoid factor, and radiographs of the lumbosacral spine and
      sacroiliac joints and of symptomatic peripheral joints were examined. RESULTS:
      16/17 (94%) patients reported some kind of back pain and 10/17 (59%) peripheral
      joint symptoms during the follow up. Two patients had unilateral grade 1
      sacroiliitis, one patient grade 4 sacroiliitis, and one patient bilateral grade 2
      sacroiliitis. In one patient the disease had progressed to ankylosing spondylitis
      (AS), and in another to chronic spondyloarthropathy. In addition, two patients
      had small erosions in radiocarpal joints. No statistically significant
      differences were found between placebo and lymecycline groups in the development
      of chronic arthritis, sacroiliitis, or AS. CONCLUSION: The results of the initial
      study showed that long term treatment with lymecycline in patients with acute ReA
      decreased the duration of arthritis in those with Chlamydia trachomatis triggered
      ReA, but not in other patients with ReA. Ten years after the acute arthritis one
      patient had developed AS, and three had radiological sacroiliitis, three patients
      had radiological changes at peripheral joints. Long term lymecycline treatment
      did not change the natural history of the disease.

PMID- 12810430
TI  - Clinical value of gallium-67 scintigraphy in assessment of disease activity in
      Wegener's granulomatosis.
AB  - BACKGROUND: Diagnosis of active pulmonary and paranasal involvement in patients
      with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of
      gallium-67 scintigraphy in WG is unclear. OBJECTIVE: To evaluate the added
      diagnostic value of gallium-67 scintigraphy in patients with WG with suspected
      granulomatous inflammation in the paranasal and chest regions. METHODS:
      Retrospectively, the diagnostic contribution of chest and head planar gallium
      scans in 40 episodes of suspected vasculitis disease activity in 28 patients with
      WG was evaluated. Scans were grouped into normal or increased uptake for each
      region. Histological proof or response to treatment was the "gold standard" for
      the presence of WG activity. RESULTS: WG activity was confirmed in 8 (20%)
      episodes, with pulmonary locations in three, paranasal in four, and both in one
      (n=7 patients); all these gallium scans showed increased gallium uptake
      (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36
      scans (specificity 64%), and negative for paranasal activity in 13/16 scans
      (specificity 81%) in episodes without WG activity. Positive predictive value of
      WG activity for lungs and paranasal region was 24% and 63%, respectively,
      negative predictive value was 100% for both regions. False positive findings were
      caused by bacterial or viral infections. CONCLUSION: Gallium scans are clinically
      helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of
      chest and nasal region has a high sensitivity for the detection of disease
      activity in WG. However, because of positive scans in cases of bacterial or viral
      infections, specificity was lower.

PMID- 12810431
TI  - Overexpression of transcripts containing LINE-1 in the synovia of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To identify novel diagnostic markers by comparing gene expression in
      rheumatoid (RA) and reactive arthritis (ReA) synovium. METHODS: Synovial biopsy
      specimens were obtained by needle arthroscopy from the knees of 10 patients with
      either RA or ReA. RNA was isolated from the biopsy specimens and cDNA synthesised
      for analysis using a customised cDNA macroarray. Confirmatory analysis was
      performed using in situ hybridisation on a second set of synovial samples.
      RESULTS: Two unique transcripts (ReXS1 and fibronectin) were consistently more
      abundant in ReA and three homologous transcripts were more abundant in RA. The
      latter all mapped within long interspersed nucleotide elements (LINE-1), that
      form one of the families of repetitive sequences in the human genome.
      CONCLUSIONS: The abundance of transcripts containing LINE-1 in the RA synovium
      may be an epiphenomenon or may have pathogenic significance. Further work is
      required to determine the identity of the full length transcript(s) before its
      use as a diagnostic marker in RA can be assessed.

PMID- 12810432
TI  - Comparison between women and men with recent onset rheumatoid arthritis of
      disease activity and functional ability over two years (the TIRA project).
AB  - OBJECTIVE: To describe the course of recent onset rheumatoid arthritis (RA) and
      to compare consequences of the disease in men and women. METHODS: 284 patients
      with recent onset RA were followed up prospectively for two years from the time
      of diagnosis. Measures of disease activity (for example, 28 joint disease
      activity score (DAS28), C reactive protein, morning stiffness, physician's global
      assessment) and function outcome (for example, range of movement, hand function,
      walking time) were determined. The patients' self reported assessment of
      functional capacity (Health Assessment Questionnaire (HAQ)) and grading of
      wellbeing and pain (visual analogue scale) were registered. Changes over time and
      differences between men and women were evaluated. RESULTS: Improvements were seen
      for all variables within the first three months. Disease activity then remained
      unchanged. Function variables followed the same pattern during the first year,
      but then tended to worsen. HAQ scores were similar at baseline, but significantly
      worse in women than in men at the one and two year follow ups. CONCLUSIONS:
      Disease activity was well managed and had improved substantially after two years,
      whereas function seemed slowly to deteriorate. Although disease variables were
      similar for men and women, functional ability (HAQ) had a less favourable course
      in women.

PMID- 12810433
TI  - Erosion healing in rheumatoid arthritis after anakinra treatment.

PMID- 12810434
TI  - Cortisol elimination from plasma in premenopausal women with rheumatoid
      arthritis.
AB  - OBJECTIVE: To test the hypothesis that cortisol elimination from plasma can
      contribute to relatively low cortisol in premenopausal women with rheumatoid
      arthritis (RA). METHODS: Twelve premenopausal female patients with RA (39.8 (1.8)
      years) and nine healthy control women matched for age and body mass index (42
      (3.3) years) were enrolled in the study. None of the patients had previously been
      receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg
      by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood
      and saliva samples were drawn six hours after injection of hydrocortisone. Plasma
      and salivary cortisol were measured. RESULTS: Dexamethasone administration
      suppressed plasma cortisol concentrations to an almost undetectable level in all
      subjects, except one with RA. In this subject, a raised concentration of plasma
      cortisol was verified by repeated analysis despite the fact that cortisol
      concentration in the saliva sample measured simultaneously was not raised. No
      significant difference in the disappearance curve of cortisol in plasma or in
      salivary cortisol levels was found between the patients with RA and the healthy
      controls. CONCLUSIONS: The profile of disappearance of total cortisol from
      plasma, and salivary cortisol levels during the elimination phase after its
      intravenous administration, are unchanged in premenopausal women with RA.
      Alterations in cortisol clearance are not likely to have a role in cortisol
      availability in patients with RA.

PMID- 12810435
TI  - Inhibition of arthritis by systemic administration of endostatin in passive
      murine collagen induced arthritis.
AB  - OBJECTIVE: To investigate the arthritis inhibiting effect of endostatin, known to
      have potent antiangiogenic activity, systemically given to animal models of
      rheumatoid arthritis (RA). METHODS: Four kinds of monoclonal anti-type II
      collagen antibody followed by lipopolysaccharide (LPS) three days later were
      given to 6 week old, female Balb/c mice to induce arthritis. Three groups of mice
      received 0.2 mg/kg/day, 2 mg/kg/day, and 10 mg/kg/day of endostatin,
      respectively, whereas a control group received phosphate buffered saline (PBS).
      Endostatin or PBS was given for 13 days, starting before the development of
      arthritis. Arthritis was evaluated by arthritis scores and hind paw thicknesses.
      Mice were killed for histological examination on the 22nd day after the
      administration of monoclonal anti-type II collagen antibody. RESULTS: Arthritis
      developed within three days after LPS administration in both the control and
      endostatin treatment groups. No difference in the development rate of arthritis
      was noted between the control and endostatin treatment groups. Arthritis scores
      remained significantly lower in the endostatin 10 mg/kg/day group than in the
      control group. Hind paw thicknesses also remained significantly smaller in the
      endostatin 10 mg/kg/day group than in the control group. Histopathological
      examination showed that synovial thickening and subchondral bone erosion improved
      more in the endostatin treatment groups than in the control group. CONCLUSION:
      The systemic administration of endostatin had an arthritis inhibiting effect in
      RA animal models. Endostatin inhibited, in particular, pannus formation and bone
      destruction.

PMID- 12810436
TI  - Efficacy of infliximab in psoriatic arthritis resistant to treatment with disease
      modifying antirheumatic drugs: an open pilot study.

PMID- 12810437
TI  - Twenty eight joint count disease activity score in recent onset rheumatoid
      arthritis using C reactive protein instead of erythrocyte sedimentation rate.

PMID- 12810438
TI  - Horner's syndrome as an initial manifestation of Takayasu's arteritis.

PMID- 12810439
TI  - Kaposi's sarcoma associated with tumour necrosis factor alpha neutralising
      therapy.

PMID- 12810440
TI  - Factors influencing uptake of influenza vaccination in patients with rheumatoid
      arthritis.

PMID- 12810441
TI  - Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with
      rheumatoid arthritis treated with infliximab and low dose methotrexate.

PMID- 12810442
TI  - Anticardiolipin antibodies in acute multifocal posterior placoid pigment
      epitheliopathy.

PMID- 12810443
TI  - Multifocal lymphadenopathy associated with severe Kawasaki disease: a difficult
      diagnosis.

PMID- 12810444
TI  - Brain abscess in rheumatoid arthritis.

PMID- 12810445
TI  - Overlap connective tissue disease, pulmonary fibrosis, and extensive subcutaneous
      calcification.

PMID- 12810446
TI  - Early descriptions of Adamantiades-Behcet's disease.

PMID- 12810447
TI  - Polymicrobial septic arthritis in a patient with Wilson's disease.

PMID- 12810448
TI  - Reduction in plasma homocysteine level in patients with rheumatoid arthritis
      given pulsed glucocorticoid treatment.

PMID- 12810449
TI  - Progress in the treatment of gastrointestinal cancer.

PMID- 12810450
TI  - Epidemiology, treatment and chemoprevention in colorectal cancer.
AB  - In Western countries, colorectal cancer (CRC) is second only to cancer of the
      lung as a cause of death from malignancy, and affects perhaps one in 20 of the
      population. In the pre-chemotherapy era, advances in surgery and earlier
      presentation led to some improvement in survival. However, no more than 60% of
      CRC patients can expect to be alive at 5 years. Adjuvant chemotherapy in stage
      III disease is of proven benefit. In metastatic CRC, chemotherapy extends disease
      free and overall survival compared with best supportive care alone, and improves
      quality of life. In palliation, infusional 5-fluorouracil (5-FU) is more active
      than bolus regimens and is less toxic. Several new cytotoxic agents show promise
      in CRC. Notable among them is irinotecan, which extends survival both when used
      as a single agent second-line versus best supportive care alone, and when added
      to 5-FU/folinic acid in the first-line setting. Much CRC is familial, raising the
      prospect of targeted screening to aid early detection. Since the molecular events
      leading to CRC have become better characterized, there is also the possibility of
      developing chemoprotective agents.

PMID- 12810451
TI  - Metastatic colorectal cancer: integrating irinotecan into combination and
      sequential chemotherapy.
AB  - The chemotherapy of metastatic colorectal cancer (CRC) has undergone a succession
      of refinements. Through the biochemical modulation of 5-fluorouracil (5-FU) with
      folinic acid (FA), the use of infusional rather than bolus regimens and the
      combination of 5-FU/FA with other active agents (notably irinotecan), first-line
      response rates (RRs) of 40% can be achieved, with patients surviving up to 17
      months. Significant benefits on survival are also seen with second-line
      chemotherapy. The question of how best to sequence combination chemotherapy was
      addressed in a recent trial in which patients were randomized to receive either
      an irinotecan-based combination with 5-FU/FA (FOLFIRI) followed by an oxaliplatin
      based combination (FOLFOX), or the two regimens in the reverse order. In both
      arms, RRs were greater than 50% and median survival exceeded 20 months. The
      primary end point was time to progression after two lines of treatment, and this
      was not significantly different. However, the sequence FOLFIRI followed by FOLFOX
      appears preferable because of the better tolerability of FOLFIRI in first-line
      use. Use of the sequence FOLFIRI/FOLFOX is also supported by the greater chance
      of a second-line response with FOLFOX. Concern has been expressed about the
      safety of irinotecan combined with bolus 5-FU/FA. Infusional regimens have a
      better risk/benefit ratio than bolus regimens. However, the adverse event profile
      with both approaches is manageable, and irinotecan plus 5-FU/FA can be considered
      one standard of care in metastatic CRC.

PMID- 12810452
TI  - Chemotherapy and surgery: new perspectives on the treatment of unresectable liver
      metastases.
AB  - Liver metastases concern half of patients with colorectal cancer, and are
      frequently unresectable, jeopardizing patient outcome. Owing to increased
      efficacy, chemotherapy can render initially inoperable patients amenable to
      potentially curative resection. The 34% 5-year and 20% 10-year survival of
      patients resected following neoadjuvant chronomodulated chemotherapy with 5
      fluorouracil, folinic acid and oxaliplatin is similar to that of patients whose
      disease was operable at diagnosis. Recently, a group of 16 patients were treated
      with irinotecan and became resectable after treatment. Their survival (56% at 3
      years) matches that of patients treated with other forms of chemotherapy. The
      poor prognosis of patients with non-resectable hepatic metastases might now be
      improved by the combination of chemotherapy and surgery.

PMID- 12810453
TI  - Irinotecan in metastatic colorectal cancer: dose intensification and combination
      with new agents, including biological response modifiers.
AB  - Phase I/II studies suggest that the combination of irinotecan with capecitabine
      is feasible and has promising activity. Diarrhea and neutropenia are dose
      limiting. Overall response rates (RRs) in the 40% to 60% range are seen from
      preliminary data. Work in progress is assessing the combination of irinotecan
      with UFT/leucovorin (LV). The use of irinotecan together with raltitrexed is also
      being investigated, as is its combination with oxaliplatin. Two phase II studies
      of irinotecan plus oxaliplatin in second-line patients report median survivals of
      11-12 months. It seems possible to safely escalate the dose of single-agent
      irinotecan to 500 mg/m(2) in patients showing good tolerance of the drug.
      Irinotecan can be used in combination with LV5FU2 at doses up to 260 mg/m(2),
      especially if only one bolus of 5-fluorouracil (5-FU) is given. Control of tumor
      growth is achieved in 90% of patients. Preliminary data suggest that regimens
      based on 5-FU/LV and irinotecan can safely be combined with the anti-epidermal
      growth factor receptor (EGFR) antibody cetuximab. In patients with EGFR-positive
      tumors, this may prove an effective means of increasing response rate or
      combating treatment resistance. Following evidence that COX-2 inhibition can slow
      progression in familial adenomatous polyposis, celecoxib is to be studied in
      metastatic colorectal cancer (CRC). In vitro, the cyclin-dependent kinase
      inhibitor flavopiridol enhances the induction of apoptosis by chemotherapy.
      Clinically, it can safely be administered with irinotecan, and studies in CRC are
      planned.

PMID- 12810454
TI  - Colorectal cancer in the adjuvant setting: perspectives on treatment and the role
      of prognostic factors.
AB  - In patients with stage III colorectal cancer (CRC) who have undergone potentially
      curative resection, adjuvant treatment with 6 months' of 5-fluorouracil (5-FU)
      plus folinic acid (FA) is generally accepted as standard treatment and leads to a
      5% to 10% improvement in absolute survival when compared with a no-chemotherapy
      control. In stage II CRC, the benefit of adjuvant chemotherapy has yet to be
      established. In metastatic CRC, randomized trials of irinotecan have consistently
      demonstrated that use of the drug, either alone or in combination with 5-FU/FA,
      prolongs survival. To investigate whether this benefit can be extended to
      patients with earlier disease, a series of multicenter trials are randomizing
      stage III colon cancer patients to adjuvant 5-FU/FA regimens with or without the
      addition of irinotecan. The role of adjuvant irinotecan is also being assessed in
      stage II colon cancer and in patients with rectal tumors. The risk/benefit ratio
      of adjuvant therapy in both stage III and stage II disease would be decreased if
      patients at the highest risk of relapse could be identified. Data from
      retrospective analyses suggest that DNA indexes, angiogenesis and some
      genetic/biological markers (loss of heterozygosity at chromosome 18 and the
      presence of microsatellite instability) identify prognostic differences in colon
      cancer patients. Their value as a guide to the intensity of adjuvant therapy
      required should be tested by randomized trial, as should the use of markers such
      as thymidilate synthase overexpression as a means of tailoring drug choice to
      tumor characteristics.

PMID- 12810455
TI  - Gastric cancer: epidemiology, pathology and treatment.
AB  - Gastric cancer incidence and mortality has fallen dramatically over the last 50
      years in many regions, but remains the second most common cancer worldwide.
      Despite a marked decline in fundic and distal tumors, there is a rising incidence
      of adenocarcinomas of the gastroesophageal junction and gastric cardia,
      particularly in Western nations. This may imply that there are in fact two
      diseases differing from each other in epidemiology, etiology, pathology and
      clinical expression. While surgical resection remains the cornerstone of gastric
      cancer treatment, the optimum extent of nodal resection remains controversial,
      with randomized studies failing to show that the D2 procedure improves survival
      when compared with D1 dissection. The high rate of recurrence and poor survival
      following surgery provides a rationale for the early use of adjuvant treatment.
      Adjuvant chemotherapy or adjuvant radiotherapy, when used alone, do not improve
      survival following resection. However, the results of the recent Intergroup 0116
      study are promising in showing that the combination of 5-fluorouracil (5-FU)
      based chemotherapy with radiotherapy significantly prolongs disease-free and
      overall survival when compared with no adjuvant treatment. In advanced gastric
      cancer, chemotherapy enhances quality of life and prolongs survival when compared
      with best supportive care. There is no agreed standard of treatment in this
      setting. Of the commonly used regimens, epirubicin plus cisplatin and 5-FU (ECF)
      probably has the strongest claim to this role. However, there is a pressing need
      for new agents, both cytotoxic and molecularly targeted, to be assessed in both
      the advanced and adjuvant settings.

PMID- 12810456
TI  - Irinotecan in the treatment of gastric cancer.
AB  - Chemotherapy has a proven palliative role in advanced gastric cancer,
      significantly improving quality of life and prolonging survival compared with
      best supportive care alone. Although there is no standard of treatment, 5
      fluorouracil (5-FU)/cisplatin doublets and the combination of epirubicin,
      cisplatin and 5-FU (ECF) have both achieved response rates in the range of 40-50%
      and median overall survival of 8-10 months. Either could claim the status of a
      reference regimen. Single-agent irinotecan achieved response rates (RR) of 18%
      and 23% in phase II studies, and 48% when combined with cisplatin. However, a
      randomized trial of irinotecan plus cisplatin versus irinotecan plus 5-FU/folinic
      acid (FA) showed that the latter regimen achieved a higher RR (34% versus 28%)
      and significantly longer median survival (10.7 versus 6.9 months). Hematological
      toxicity was lower with the irinotecan/5-FU/FA combination. This regimen has
      therefore been taken forward into a randomized phase III comparison against a 5
      FU/cisplatin doublet. Use of irinotecan-based combinations should also be
      investigated as an adjuvant treatment (probably in combination with radiotherapy)
      and in the neoadjuvant setting.

PMID- 12810457
TI  - Docetaxel-based chemotherapy in the treatment of gastric cancer.
AB  - Docetaxel-based chemotherapy appears to have considerable promise in advanced
      gastric cancer. In phase II studies of single agent docetaxel, response rates
      (RRs) of 17% to 24% have been achieved in previously untreated patients.
      Importantly, RRs of 20% to 22% are seen in second-line treatment. Work by a Swiss
      and Italian collaborative group has shown that the combination of docetaxel 85
      mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks is quite active, achieving an RR
      of 55% and median survival of 9 months. Hematotoxicity was the main adverse event
      but was manageable. In other respects the docetaxel/cisplatin doublet (TC) was
      relatively well tolerated. The same group demonstrated that continuous infusion
      of 5-fluorouracil (5-FU) 300 mg/m(2) can be given on 2 weeks out of 3 to patients
      receiving TC. The addition of 5-FU, by this schedule, to TC (TCF) does not
      increase hematological toxicity, and does not compromise the tolerability of TC.
      An overall RR of 55% has been reported with TCF. A randomized phase II comparison
      of TC or TCF versus an ECF (epirubicin/cisplatin/5-FU) control arm is ongoing and
      should lead to a randomized phase III trial comparing TC or TCF with ECF. In an
      already completed international randomized phase II comparison of TC versus TCF
      (TAX-325), the three-drug combination proved significantly more active (RR 54%
      versus 32% with TC, among patients treated per protocol). Time to progression was
      also longer for TCF. Gastrointestinal (but not hematological) toxicity was less
      with TC. TCF was chosen for ongoing phase III comparison against a control 5
      FU/cisplatin arm. It is possible that data from these randomized studies will
      confirm the value of docetaxel-based chemotherapy in advanced gastric cancer and
      that docetaxel combinations will also be effective in the multidisciplinary
      efforts to cure earlier stage cancer.

PMID- 12810458
TI  - Future strategies and adjuvant treatment of gastric cancer.
AB  - The most recent meta-analyses of adjuvant chemotherapy in resected gastric cancer
      suggest that systemic treatment may achieve a small, but statistically
      significant and probably clinically relevant, reduction in risk of death.
      However, this still needs confirmation in a large, prospective, well-designed
      phase III study. The recent Intergroup 0116 study, conducted in USA, of combined
      post-operative chemoradiotherapy demonstrated significantly improved disease-free
      and overall 5-year survival compared with an observation-only arm. However, 54%
      of patients appeared to have had suboptimal surgery. The fact that adjuvant
      therapy reduced locoregional (and not distant) relapse suggests that its benefit
      may lie in compensating for inadequate dissection. Combined modality therapy was
      associated with moderate toxicity, but a high requirement for changes in
      radiation planning. Therefore, the role and feasibility of adjuvant radiotherapy
      needs to be confirmed in patients operated on in Western Europe. Several
      approaches to the development of early systemic therapy in gastric cancer are
      being pursued. These include the evaluation of cisplatin-based adjuvant regimens,
      the use of neoadjuvant treatment, the incorporation into adjuvant and neoadjuvant
      regimens of newer cytotoxics such as docetaxel and irinotecan, and the assessment
      of novel, molecularly targeted agents such as the epidermal growth factor
      receptor and angiogenesis inhibitors.

PMID- 12810459
TI  - Current treatments and future perspectives in colorectal and gastric cancer.
AB  - Given the high rate of distant spread, effective systemic therapy is key to
      improving survival in patients with colorectal cancer (CRC). The past 40 years
      have seen progress. The addition of folinic acid (FA) to 5-fluorouracil (5-FU),
      the use of infusional rather than bolus 5-FU, and the combination of new active
      agents such as irinotecan and oxaliplatin with 5-FU/FA have each led to an
      increase in activity. In trials of current combination regimens first-line,
      response rates (RRs) in excess of 50% and median survival durations longer than
      16 months are seen. A recent controlled trial suggests that overall time to
      progression is maximized and toxicity minimized when an irinotecan/5-FU/FA
      combination is used first-line, followed by an oxaliplatin/ 5-FU/FA combination
      on progression. In the adjuvant setting, 5-FU/FA is the standard of care in stage
      III disease but of uncertain value in stage II patients. The role of new agents
      such as irinotecan in adjuvant regimens is being assessed. Use of highly active
      chemotherapy in patients with unresectable disease (particularly liver
      metastases) achieves responses that allow a subset of patients to proceed to
      potentially curative surgery. The emergence of novel agents targeted at processes
      such as tumor angiogenesis will complement cytotoxic chemotherapy, while improved
      understanding of tumor biology should enable agents to be selected according to
      the likely sensitivity of the disease in a particular patient. In gastric cancer
      also, surgery remains the only potentially curative treatment. The extent of
      dissection required is debated, as is the potential benefit of adjuvant
      chemoradiotherapy (indeed the degree of resection may interact with the effect of
      adjuvant treatment). In untreated metastatic gastric cancer, median survival is 3
      4 months. This can be increased to around 10 months using chemotherapy. Quality
      of life is also enhanced. There is no clearly defined standard of care. However,
      some form of cisplatin/5-FU combination can serve as a reference regimen. As
      single agents, both irinotecan and docetaxel achieve RRs of around 20% in
      metastatic CRC. In combination with cisplatin and/or 5-FU a very high and
      promising RR is achieved. The promise of these agents in combination with 5-FU
      and 5-FU plus cisplatin is currently being tested in phase III trials.

PMID- 12810461
TI  - Dissecting the "endoscopic neck".

PMID- 12810462
TI  - Endoscopic selective neck dissection in a porcine model.
AB  - OBJECTIVE: To investigate the feasibility of accomplishing a selective neck
      dissection (SND) endoscopically. STUDY DESIGN: Prospective, nonrandomized
      experimental investigation in a porcine model. METHODS: Unilateral endoscopic
      SNDs were performed in Yorkshire pigs. A spacious operative pocket was developed
      using a combination of hernia balloon expansion followed by low-pressure (4 mm
      Hg) carbon dioxide insufflation. The sternomastoid muscle, thymus, submandibular
      gland, lymph nodes, and fibrofatty tissue were removed in a procedure
      approximating a human SND. Data (operative time, blood loss, arterial blood gas
      values, weight of the specimen, and complications) were prospectively recorded.
      The specimens were analyzed by a pathologist, and the number and size of lymph
      nodes were recorded. RESULTS: Fourteen endoscopic SNDs were successfully
      performed. No conversions to open surgery were necessary. The median operative
      time was 131 minutes (range, 95-235 minutes). The median estimated blood loss was
      4 mL (range, 0-150 mL). The mean +/- SD specimen weight was 42.9 +/- 8.3 g; the
      mean number +/- SD of nodes retrieved from the neck specimen was 4.8 +/- 2.2, and
      the mean +/- SD maximal nodal dimension was 2.4 +/- 0.5 cm. The arterial PCO2
      increased by an average of only 3.9 mm Hg from the beginning to the end of the
      surgery; correspondingly, the pH fell by only 0.02. There were no major
      complications, and no animals had to be euthanized prior to the completion of the
      procedure. CONCLUSIONS: Endoscopic neck dissection in a porcine model can be
      accomplished with a combination of strategies to overcome the dilemma of creating
      and maintaining an operative pocket. The merger of SND with endoscopic technology
      offers the promise of truly minimally invasive surgery for the node-negative
      neck.

PMID- 12810463
TI  - Combination nonviral interleukin 2 gene therapy and external-beam radiation
      therapy for head and neck cancer.
AB  - OBJECTIVES: To demonstrate that the combination of nonviral murine interleukin 2
      (mIL-2) gene therapy and external-beam radiation therapy (XRT) have an enhanced
      therapeutic effect for the treatment of head and neck squamous cell carcinoma
      (HNSCC) in an orthotopic murine model and to elucidate the mechanism of action.
      METHODS: Randomized, controlled studies in the murine orthotopic model of HNSCC.
      Squamous cell carcinoma VII cells were injected into the floor of the mouth to
      establish tumors in immunocompetent mice. The intervention groups were treated
      with mIL-2, radiation therapy, empty plasmid, no treatment, combination mIL
      2/XRT, and combination empty plasmid/XRT. Nonviral mIL-2 gene transfer was
      performed on days 5 and 9. The XRT was administered to the assigned groups 24
      hours after first mIL-2 delivery. The mice were killed on day 13. Tumors and
      local lymph nodes were harvested and evaluated. Primary and secondary cytokine
      expression, cytotoxic T-lymphocyte activity, and apoptosis were assayed. RESULTS:
      The combination mIL-2/XRT demonstrated a significant increase in antitumor
      effects compared with single therapy or controls. Increased expression levels of
      primary and secondary cytokines were found in the group treated with mIL-2, and
      this effect was preserved when mIL-2 treatment was combined with XRT. Combination
      therapy significantly increased apoptosis compared with monotherapy. CONCLUSIONS:
      The present study demonstrates that combination mIL-2/XRT generates potent
      antitumor immune responses and significantly increases apoptosis in an orthotopic
      murine model of HNSCC. Further optimization of this strategy is warranted as well
      as consideration for human clinical trials.

PMID- 12810464
TI  - Transoral laser surgery for early glottic cancers.
AB  - OBJECTIVE: To demonstrate the oncologic safety of transoral endoscopic laser
      surgery in early glottic cancers. PATIENTS: The study included 107 patients with
      early glottic cancers. The disease was in situ in 21 (19.6%) and infiltrative in
      86 (80.4%), of which 52 (48.6%) were stage T1a, 17 (15.9%) were T1b, 13 (12.1%)
      were T2, and 4 (3.7%) were TX lesions. One hundred three patients (96.3%) were
      treated primarily, whereas 4 patients (3.7%) were operated on after radiotherapy
      failure. Anatomically, 77 lesions (72.0%) involved the anterior or middle third
      of the vocal cord; 14 lesions (13.1%) involved a single cord and the anterior
      commissure; 4 "horseshoe" lesions (3.7%) involved both cords and the anterior
      commissure; 7 lesions (6.5%) involved the posterior third of the cord reaching
      the vocal process of the arytenoid; and 5 cases (4.7%) involved both cords
      separately. RESULTS: There were 17 (15.9%) local recurrences (10 among patients
      with single cord lesions, 5 among patients with cord and anterior commissure
      lesions, and 2 among patients with lesions involving both cords), and 1 regional
      recurrence. One hundred one patients (94.4%) were alive and disease free at a
      median of 40.7 months. Three patients (2.8%) were alive with disease. One patient
      (0.9%) died of other causes. Two patients (1.9%) died of a second primary cancer.
      The overall larynx preservation rate was 92.5%. Recurrence-free survival was
      86.6% at 2 years, 84.1% at 5 years, and 78.1% at 10 years. CONCLUSION: Transoral
      laser surgery is an oncologically safe, function-preserving modality for
      treatment of early glottic cancers.

PMID- 12810465
TI  - Effect of parenteral aminoglycoside administration on dark cells in the crista
      ampullaris.
AB  - OBJECTIVE: To observe the early and late effects of the parenteral administration
      of aminoglycosides on the dark cells of ampullae in the inner ear. STUDY DESIGN:
      Comparative study of the histopathologic characteristic of human temporal bones.
      SUBJECTS AND METHODS: Sixty-three temporal bones from 44 subjects (age range, 16
      81 years) were examined by light microscopy. Three groups of temporal bones were
      selected for this study: group 1, 30 "normal" temporal bones from 22 subjects
      (mean age, 59 years; age range, 25-81 years) with no history or histopathologic
      findings of otologic disease or ototoxic drug use; group 2, 14 temporal bones
      from patients who received aminoglycoside treatment within 2 weeks before death;
      and group 3, 19 temporal bones from patients who received aminoglycoside
      treatment between 2 weeks and 6 months before death. RESULTS: The mean +/- SD
      number of dark cells in group 1 was 15.0 +/- 2.47; in group 2, it was 17.3 +/-
      1.93 in the subjects who received gentamicin sulfate and 15.0 +/- 3.08 in those
      who received kanamycin sulfate and tobramycin; in group 3, it was 14.6 +/- 1.67
      in the subjects who received gentamicin and 15.2 +/- 2.31 in those who received
      kanamycin and tobramycin. The overall difference between the 3 groups was not
      statistically significant (P =.07). The cytologic characteristics of dark cells
      were similar in all 3 groups. The number of dark cells showed a decline with
      increasing age in group 1. CONCLUSIONS: The result of this study suggests that
      the treatment period was probably too short to destroy the dark cells. Therefore,
      long-term aminoglycoside therapy may be necessary to get a more permanent result.

PMID- 12810466
TI  - Efficacy of the Semont maneuver in benign paroxysmal positional vertigo.
AB  - OBJECTIVES: To assess the efficacy of the Semont maneuver in the treatment of
      benign paroxysmal positional vertigo (BPPV) of the posterior semicircular canal
      and to evaluate the possible effect of various factors on the efficacy of this
      maneuver. DESIGN AND SETTING: Retrospective study in an outpatient clinic.
      PATIENTS: Two hundred seventy-eight patients presenting with symptomatic,
      unilateral BPPV of the posterior semicircular canal, exclusively treated with the
      Semont maneuver. INTERVENTIONS: During the first consultation, each patient was
      treated with a Semont maneuver. When BPPV persisted, this maneuver was repeated
      during follow-up visits, performed at weekly intervals. MAIN OUTCOME MEASURES:
      Patients were considered cured when vertigo disappeared within 30 days (allowing
      up to 4 maneuvers). RESULTS: More than 90% of patients were cured after a maximum
      of 4 maneuvers, and 83.5% were cured after only 2 maneuvers. The efficacy of the
      maneuver decreased each time it was repeated (from 62.6% at the first maneuver to
      18.2% at the fourth). The duration of symptoms before initial consultation and
      the etiology of BPPV had a significant effect on the maneuver's efficacy (P<.001
      and P =.002, respectively), whereas age (P =.12), sex (P =.06), and affected side
      (P =.20) had no effect. CONCLUSIONS: The Semont maneuver demonstrated a 90.3%
      cure rate after a maximum of 4 sessions. Patients consulting late (>6 months
      after the beginning of symptoms) or having traumatic BPPV had lower recovery
      rates than patients without these factors (74.7% vs 96.5%).

PMID- 12810467
TI  - Anatomical evidence of microbial biofilms in tonsillar tissues: a possible
      mechanism to explain chronicity.
AB  - CONTEXT: Bacteria within biofilms are resistant to host defenses and antibiotics.
      The presence of bacterial biofilms within the tissue and crypts of inflamed
      tonsils may explain the chronicity and recurrent characteristics of some forms of
      tonsillitis. OBJECTIVE: To determine if microbial biofilms occur within
      clinically abnormal tonsils. DESIGN: In this study, we evaluated the
      histomorphological appearance of 19 human tonsils for evidence of biofilm
      formation using light and transmission electron microscopy. SUBJECTS: Human
      tissues were collected during surgical tonsillectomy. Fifteen specimens were
      removed because of a history of repeated infections, and 4 were removed because
      of hypertrophy and obstruction. INTERVENTIONS: No interventions were used in this
      study. MAIN OUTCOME MEASURE: Histological and ultrastructural evidence of
      bacterial biofilms within the crypts of tonsils. RESULTS: Gram-positive and gram
      negative bacteria were seen within otherwise acellular deposits among crypts of
      11 of 15 infected tonsils. Regions of accumulated bacteria possessed the
      ultrastructural appearance of typical amorphous polysaccharide biofilm matrix.
      Small clusters of bacterial colonies were seen in 3 of 4 tonsils removed because
      of hypertrophy. CONCLUSIONS: There is strong anatomical evidence for the presence
      of bacterial biofilms in chronically diseased tonsils. Because sessile bacteria
      within biofilms are resistant to host defenses and antibiotics, bacterial
      biofilms within tonsils may explain the chronicity and recurrent nature of some
      forms of tonsillitis.

PMID- 12810468
TI  - Intravenous sedation vs general anesthesia for pediatric otolaryngology
      procedures.
AB  - OBJECTIVE: To compare efficacy, safety, and hospital charges for common pediatric
      otolaryngology procedures with the use of intravenous sedation (IVS) vs general
      anesthesia (GA). DESIGN: Retrospective chart study. SETTING: Hospital-based
      pediatric otolaryngology practice. PATIENTS: Patients younger than 18 years who
      underwent tympanostomy tube removal and/or patch myringoplasty with absorbable
      gelatin sponge, nasal ciliary biopsy, fine-needle aspiration, or other minor
      procedures between September 1, 1998, and August 31, 2001. INTERVENTIONS:
      Procedures performed in 2 settings: outpatient clinic with IVS or operating room
      with GA. MAIN OUTCOME MEASURES: Procedure completion rate, tympanic membrane
      perforation rate after ear procedures, complications, and hospital charges.
      RESULTS: Of 103 procedures, 54 were performed with IVS and 49 with GA. Within the
      GA group, 32 of 49 patients had additional operations performed and were excluded
      from analysis of safety and hospital charges. Procedure completion rate was 100%
      in both groups. The most common procedure was tympanostomy tube removal with
      patch myringoplasty (IVS, 52 ears; GA, 42 ears). The rate of persistent tympanic
      membrane perforation was similar between these groups (IVS, 7 [16%] of 45 ears;
      GA, 5 [15%] of 33; P =.96). All complications were minor and occurred at similar
      rates (IVS, 10 [19%] of 54 ears; GA, 3 [18%] of 17; P =.94). These events
      included hypoxia, airway obstruction, and bradycardia, all of which resolved
      spontaneously or responded to noninvasive interventions such as oxygen or
      repositioning. Average hospital charges were significantly higher for the GA
      group (IVS, $356.22; GA, $1516.55; P<.001). CONCLUSION: Various procedures can be
      performed safely, effectively, and with decreased hospital charges with the use
      of IVS administered by a pediatric sedation service.

PMID- 12810469
TI  - Diagnosis and therapy for airway obstruction in children with Down syndrome.
AB  - OBJECTIVES: To document the causes of upper airway obstruction in a population of
      children with Down syndrome and to highlight the role of associated
      comorbidities. DESIGN AND SETTING: Review of 23 cases involving children with
      Down syndrome who were referred for upper airway obstruction over a 2(1/2)-year
      period to the Pediatric Otolaryngology Service of the University of New Mexico,
      Albuquerque. METHODS: Data on the following variables were obtained: reason for
      referral, demographics, diagnosis, surgical procedures, complications, and
      comorbidities. RESULTS: The children ranged in age from 1 day to 10.2 years (mean
      age, 1.8 years; median age, 6 months). Thirteen children were male and 10 were
      female. None of the children had subglottic stenosis. Laryngomalacia was the
      primary diagnosis in 10 children (43%), 8 of whom were younger than 1 month.
      Obstructive sleep apnea was the primary diagnosis in 11 children (48%), 8 of whom
      were older than 2 years. All children with obstructive sleep apnea and 4 children
      with laryngomalacia had a secondary ear, nose, and throat disorder.
      Gastroesophageal reflux was a comorbidity in 14 children (61%). CONCLUSIONS: The
      causes, severity, and presentation of upper airway obstruction in children with
      Down syndrome are related to the age of the child and to associated
      comorbidities. The treatment of comorbidities and secondary ear, nose, and throat
      disorders is an integral component of the surgical management of upper airway
      obstruction in such cases.

PMID- 12810470
TI  - Pediatric tympanoplasty: effect of contralateral ear status on outcomes.
AB  - OBJECTIVE: To assess the prognostic value of different variables on the outcome
      of pediatric type I tympanoplasty. DESIGN: Retrospective review of medical
      records. SETTING: An otolaryngology department in a large urban tertiary care
      medical center. PATIENTS: We reviewed 72 ears in 60 patients who had undergone a
      type I tympanoplasty from 1987 to 2000. Patient ages ranged from 3 to 18 years.
      INTERVENTIONS: Type I tympanoplasty. MAIN OUTCOME MEASURES: We identified the
      following 3 criteria for success: (1) healing of the neotympanic graft; (2)
      healing of the graft with a postoperative air-bone gap of no greater than 20 dB;
      and (3) healing of the graft with aeration of the middle ear space. RESULTS:
      Healing occurred in 59 (82%) of the 72 neotympanic grafts; 39 (83%) of the 47
      healed ears for which a postoperative audiogram was available had an air-bone gap
      of no greater than 20 dB; and 49 (83%) of the 59 healed ears had a normally
      aerated middle ear space. A statistically significant difference in the rate of
      graft healing was identified for large perforations (76%), as well as for
      creation of an aerated middle ear space, when there was evidence of ongoing
      contralateral eustachian tube dysfunction (ie, otitis media with effusion or
      negative middle ear pressure, but not a perforation). CONCLUSIONS: Pediatric type
      I tympanoplasty can offer reasonably good chances for postoperative graft
      healing, serviceable hearing, and creation of an air-containing middle ear space
      if performed in carefully selected patients. Caution should be exercised in
      performing tympanoplasty in children with evidence of ongoing eustachian tube
      dysfunction, as evidenced by otitis media with effusion and negative middle ear
      pressure, but not perforations, in the contralateral ear.

PMID- 12810471
TI  - Cosmetic considerations in surgery for orbital subperiosteal abscess in children:
      experience with a combined transcaruncular and transnasal endoscopic approach.
AB  - OBJECTIVE: To evaluate the outcomes of a new surgical approach in children with
      acute sinusitis and medial orbital subperiosteal abscess. DESIGN: Case series.
      SETTING: Tertiary pediatric hospital. PATIENTS: Eleven children aged 6 weeks to
      13 years with orbital subperiosteal abscess and acute sinusitis who met
      indication for surgery by visual compromise and/or refractory course to medical
      therapy. INTERVENTION: The medial orbital abscess was drained via a
      transcaruncular approach, which provided access to the medial orbital wall. An
      endoscopic ethmoidectomy was also performed. MAIN OUTCOME MEASURES: Judgment of
      cosmetic appearance by surgeon and family, resolution of symptoms, length of
      hospital stay, and complications. RESULTS: All children had prompt resolution of
      symptoms after surgical drainage. Cosmetic outcome was excellent in all patients
      with no cutaneous scar or eyelid malposition. After edema and cellulitis had
      resolved, no family member could tell a difference in appearance between the
      eyes. No complications of these combined procedures were identified. One patient
      who had initially undergone transnasal endoscopic orbital drainage alone
      experienced a recurrence of infection 17 days later. He was then treated by the
      combined transcaruncular and endoscopic approach with prompt resolution of his
      symptoms. One of 4 patients treated initially with transcaruncular approach alone
      without endoscopic ethmoidectomy had recurrence of acute sinusitis and orbital
      abscess 16 months later and was successfully treated with an endoscopic approach.
      CONCLUSIONS: The combined endoscopic and transcaruncular surgical approach to
      medial orbital subperiosteal abscess and acute sinusitis provides a cosmetically
      superior outcome compared with standard orbital approaches requiring a cutaneous
      incision. The transcaruncular approach can be considered as an alternative or
      adjunct approach to the medial orbit, with the same cosmetic advantages as
      transnasal endoscopic drainage.

PMID- 12810472
TI  - Treatment of recurrent chronic hyperplastic sinusitis with nasal polyposis.
AB  - OBJECTIVE: To demonstrate the long-term efficacy of intranasal furosemide, an
      inhibitor of the sodium chloride cotransporter channel at the basolateral surface
      of the respiratory epithelial cell, vs no therapeutic intervention vs intranasal
      mometasone furoate, a corticosteroid, in preventing relapses of chronic
      hyperplastic sinusitis with nasal polyposis. DESIGN: Randomized prospective
      controlled study. Patients were examined every 6 months during follow-up (range,
      1-9 years). PATIENTS: One hundred seventy patients with bilateral obstructive or
      minimally obstructive chronic hyperplastic sinusitis with nasal polyposis.
      INTERVENTION: All patients were surgically treated in the ENT Department,
      University of Siena Medical School. One month after surgery, group 1 patients (n
      = 97) started treatment with intranasal furosemide, group 2 (n = 40) received no
      therapeutic treatment, and group 3 (n = 33) were treated with mometasone. MAIN
      OUTCOME MEASURES: Clinical and instrumental evaluation of postoperative outcomes.
      RESULTS: Seventeen (17.5%) of 97 patients in group 1, 12 (30.0%) of 40 patients
      in group 2, and 8 (24.2%) of 33 patients in group 3 experienced nasal polyposis
      relapses. We noted a prevalence of early-stage relapse in patients treated with
      furosemide or mometasone, whereas patients who did not receive any treatment
      experienced more severe grades of chronic hyperplastic sinusitis with nasal
      polyposis (P<.005). CONCLUSION: Use of intranasal furosemide represents a valid
      therapeutic treatment in the prevention of chronic hyperplastic sinusitis with
      nasal polyposis.

PMID- 12810473
TI  - Effects of nasal saline spray on human neutrophils.
AB  - BACKGROUND: Nasal saline spray (NSS) used in the treatment of rhinitis and
      sinusitis often contains the preservative benzalkonium chloride (BKC). Previous
      studies have shown that corticosteroid nasal sprays and topical decongestants
      containing BKC damage respiratory mucosa, decrease mucociliary activity, and
      inhibit neutrophil functions in vitro. OBJECTIVE: To evaluate the effects of NSS
      with BKC on human neutrophils. DESIGN: Prospective, basic science observations.
      METHODS: Human neutrophils were exposed to NSS with BKC or to phosphate-buffered
      saline (PBS) at varying times and concentrations. The cells were examined for
      morphologic changes by light microscopy and for viability as determined by trypan
      blue exclusion. Lactate dehydrogenase levels were measured to quantify neutrophil
      cell lysis. In vivo morphologic changes were studied in neutrophils obtained from
      the oral mucosa in human volunteers who rinsed their mouths with NSS or PBS.
      RESULTS: Neutrophils exposed to NSS concentrations as low as 15% showed near
      total cell lysis, and neutrophils exposed to 20% NSS demonstrated no cell
      viability by trypan blue staining. Phosphate-buffered saline-exposed cells were
      unaffected. The release of lactate dehydrogenase from lysed neutrophils increased
      sharply at NSS concentrations higher than 10% but remained stable in PBS-exposed
      cells. All neutrophils isolated from NSS oral rinses were lysed, while a mean of
      78% of neutrophils from PBS rinses showed normal morphologic structure.
      CONCLUSIONS: Nasal saline spray with BKC is toxic to human neutrophils even at
      concentrations far lower than those found in commercially available preparations.
      Saline solutions without BKC appear to be safer alternatives, and additional
      studies are needed to determine the clinical significance of these findings.

PMID- 12810474
TI  - Expression patterns of galectin-1 and galectin-3 in nasal polyps and middle and
      inferior turbinates in relation to growth regulation and immunosuppression.
AB  - BACKGROUND: The term nasal polyposis describes benign growth processes in the
      nasal and sinus mucosa, which are mainly located in the middle meatus and never
      in the inferior meatus. As a step to define the biochemical determinants relevant
      for growth regulation, we focused on endogenous lectins known for anti-apoptotic
      (galectin-3) and immunomodulatory (galectin-1) activities. DESIGN: Using computer
      assisted microscopy, we performed an immunohistochemical investigation defining
      the quantitative parameters of expression of galectin-1 and galectin-3 in 10
      nasal polyps, 10 middle turbinates, and 10 inferior turbinates, all of which were
      obtained from surgical resection. RESULTS: Our data show that galectin-3
      expression is markedly (P<.001) higher in nasal polyps than in turbinates. No
      relation to the allergic status was discovered. Galectin-1 expression is higher
      in nasal polyps than in middle turbinates (P<.001) in nonallergic patients
      compared with allergic ones (in glandular epithelium, P =.009; in connective
      tissue, P =.006). The lowest galectin-1 expression was observed in the middle
      turbinate. CONCLUSIONS: These data are in line with a positive influence of
      galectin-3 on growth and an immunoregulatory role of galectin-1, mimicking an
      increased expression dependent on glucocorticoid.

PMID- 12810475
TI  - Utility of tonsillectomy in 2 patients with the syndrome of periodic fever,
      aphthous stomatitis, pharyngitis, and cervical adenitis.
AB  - OBJECTIVES: To review the various causes of period fever in childhood, including
      the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical
      adenitis (PFAPA), and to examine the value of tonsillectomy in the treatment of
      PFAPA syndrome. DESIGN: Retrospective case series. SETTING: Urban and tertiary
      care referral children's hospital. PATIENTS: Two patients who underwent
      tonsillectomy for presumed recurrent adenotonsillitis were later diagnosed as
      having PFAPA syndrome. Intervention Tonsillectomy. MAIN OUTCOME MEASURE:
      Frequency of PFAPA symptoms before and after tonsillectomy. RESULTS: No
      difference was found in the frequency of PFAPA symptoms after tonsillectomy.
      CONCLUSION: Although a larger series of patients is required, our initial
      experience suggests that tonsillectomy is not always beneficial for patients with
      PFAPA syndrome.

PMID- 12810476
TI  - Clinical use of new technologies without scientific studies.

PMID- 12810477
TI  - Safety first.

PMID- 12810478
TI  - Innovative tools, regulatory bodies, and the creative surgeon.

PMID- 12810479
TI  - Pathology quiz case: cribriform-morular variant of papillary thyroid carcinoma.

PMID- 12810480
TI  - Radiology quiz case: Bezold abscess.

PMID- 12810481
TI  - Cerebrospinal fluid 14-3-3 protein: variability of sporadic Creutzfeldt-Jakob
      disease, laboratory standards, and quantitation.

PMID- 12810482
TI  - Getting the spinal cord to think for itself.
AB  - Despite the interruption in communication between the brain and lower centers by
      spinal cord injury, many of the neurons engaged in generating locomotion survive.
      Several strategies have been used to activate spinal cord circuitry independent
      of the higher centers, including direct electrical stimulation, pharmacological
      agents, and training programs that involve moving the legs through the motions of
      walking. Ambulatory leg movements are achieved by these interventions, leading to
      substantial functional improvements in the subset of patients with incomplete
      spinal cord injury. The neurobiological basis for these phenomena likely involves
      activity-dependent reconfiguration of synaptic connections within the spinal
      cord. Fostering this process may lead to further benefits for individuals with
      spinal cord injury.

PMID- 12810483
TI  - Working memory in the primary visual cortex.

PMID- 12810484
TI  - Challenging the clinical utility of the 14-3-3 protein for the diagnosis of
      sporadic Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal
      neurodegenerative disorder for which there is no noninvasive and disease-specific
      test for premortem diagnosis. Previous studies have suggested that, in the proper
      clinical context, the 14-3-3 protein in cerebrospinal fluid is a reliable marker
      for sporadic CJD. OBJECTIVE: To assess the sensitivity of the cerebrospinal fluid
      14-3-3 protein test among patients with definite sporadic CJD. DESIGN AND
      SETTING: We reviewed cases of sporadic CJD referred to our institution that were
      ultimately proved by pathological examination and on which cerebrospinal fluid 14
      3-3 testing had been performed. PARTICIPANTS: Patients with CJD referred to our
      institution for clinical and/or pathological evaluation (biopsy- or autopsy
      confirmed diagnosis) from January 1, 1998, through July 15, 2002, and on whom 14
      3-3 testing had been performed. Thirty-two such patients with definite sporadic
      CJD were identified. Main Outcome Measure The 14-3-3 test results, from various
      laboratories, in these 32 patients. RESULTS: Seventeen of the 32 patients had a
      positive result for the 14-3-3 test, yielding a sensitivity of only 53%. A
      positive 14-3-3 result was significantly correlated with a shorter time between
      disease onset and the lumbar puncture for the 14-3-3 test. CONCLUSIONS: Testing
      for the 14-3-3 protein is only modestly sensitive to sporadic CJD, and we caution
      against ruling out a diagnosis of the disease on the basis of a negative 14-3-3
      result.

PMID- 12810485
TI  - Increased risk of late posttraumatic seizures associated with inheritance of APOE
      epsilon4 allele.
AB  - BACKGROUND: Late posttraumatic seizures are a common complication of moderate and
      severe traumatic brain injury. Inheritance of the apolipoprotein E (APOE)
      epsilon4 allele is associated with increased risk of Alzheimer disease,
      progression to disability in multiple sclerosis, and poor outcome after traumatic
      brain injury. OBJECTIVE: To determine whether inheritance of APOE epsilon4 is
      associated with increased risk of developing late posttraumatic seizures. DESIGN:
      Prospective study. SETTING: Neurosurgical service at an urban level I trauma
      center.Patients Patients admitted with a diagnosis of moderate and severe
      traumatic brain injury were enrolled. METHODS: Six months after injury, patients
      were contacted to determine functional outcome (according to the Glasgow Outcome
      Scale-Expanded [GOS-E]) and the presence of late posttraumatic seizures. Genotype
      at the APOE locus was determined by restriction fragment length polymorphism
      analysis. RESULTS: DNA and outcome information was obtained from 106 subjects.
      Six months after injury, 31 (29%) had a poor outcome (GOS-E score, 1-4), 47 (44%)
      had an intermediate outcome (GOS-E score, 5-6), and 28 (26%) had a favorable
      outcome (GOS-E score, 7-8). Twenty-one patients (20%) had at least 1 late
      posttraumatic seizure. The relative risk of late posttraumatic seizures for
      patients with the epsilon4 allele was 2.41 (95% confidence interval, 1.15-5.07; P
      =.03). In this cohort, inheritance of APOE epsilon4 was not associated with an
      unfavorable GOS-E score 6 (P =.47). CONCLUSIONS: Inheritance of the APOE epsilon4
      allele is associated with increased risk of late posttraumatic seizures. In this
      cohort, this risk appears to be independent of an effect of epsilon4 on
      functional outcome. A better understanding of the molecular role of APOE in
      neurodegenerative diseases may be helpful in developing antiepileptogenic
      therapies.

PMID- 12810486
TI  - Disease course of Charcot-Marie-Tooth disease type 2: a 5-year follow-up study.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) type 2 is the axonal variant of an
      inherited, sensorimotor polyneuropathy. To our knowledge, the clinical course of
      CMT type 2 has never been prospectively studied in a large group of patients.
      OBJECTIVE: To prospectively evaluate the disease course of patients with CMT type
      2. METHODS: We prospectively evaluated the disease course in patients with CMT
      type 2. Forty-three patients (24 men) of 27 families with CMT type 2 were
      included. All patients were analyzed by the same investigator at entry and after
      5 years. The standardized protocol included manual muscle testing, which could
      lead to a motor sum score of 140 points, and quantification of sensory deficit.
      Disability was assessed using the modified Rankin scale, and quality of life was
      assessed using the RAND 36-item health survey questionnaire. Eighteen families
      were tested for known mutations in the MPZ, PMP22, and GJB1 genes. RESULTS: At
      entry, the mean +/- SD age of the patients was 52 +/- 14 years, and the mean +/-
      SD duration of disease was 12 +/- 8 years. The median motor sum score
      deteriorated from 135 to 128 points (P =.02). Progression was never rapid. There
      was no sensory deterioration. The Rankin score decreased by 1 point in 16
      patients. At follow-up, more patients needed walking aids, but most patients
      remained ambulant. The number of patients with claw toes increased, whereas the
      number of patients with foot deformities such as pes cavus and short calf muscles
      remained stable. There was no correlation between deterioration and age. Analysis
      of quality of life did not show any changes. In one family, a mutation in the
      GJB1 gene was found. CONCLUSION: This prospective study shows a slow
      deterioration of muscle strength and increase in disability in CMT type 2 during
      a 5-year follow-up period.

PMID- 12810487
TI  - Temporal lobectomy in congenital porencephaly associated with hippocampal
      sclerosis.
AB  - BACKGROUND: Clinical and neuroimaging features of patients with epilepsy and
      coexisting extratemporal porencephaly and hippocampal sclerosis have been
      previously described. OBJECTIVE: To present the clinical characteristics and
      surgical outcome of 6 patients with intractable epilepsy and coexisting
      extratemporal porencephaly and hippocampal sclerosis. PATIENTS AND METHODS:
      Twenty-four patients with porencephaly and epilepsy were studied. Of these, 6 had
      an epileptogenic focus in the temporal region. All patients underwent video
      electroencephalogram monitoring, magnetic resonance imaging studies, and
      neuropsychological evaluation. Of the subset of patients with temporal lobe
      epilepsy, 1 patient underwent intracranial electroencephalogram monitoring.
      Temporal lobe resection was performed in 5 patients. Outcomes were evaluated
      using the Engel classification. RESULTS: Freedom from seizures was achieved in
      all patients. Pathologic analysis of the resected tissue confirmed the
      presurgical diagnosis of mesial temporal sclerosis. CONCLUSION: Patients with
      extratemporal porencephaly and intractable seizures should be evaluated early and
      be considered for temporal lobectomy if clinical, magnetic resonance imaging, and
      electroencephalogram findings support the diagnosis of temporal lobe onset
      seizures.

PMID- 12810488
TI  - A longitudinal study of gait and balance dysfunction in normal older people.
AB  - OBJECTIVE: To identify the causes of deteriorating gait and balance in normal
      older people. METHODS: We measured visual acuity, vestibulo-ocular responses,
      pure-tone hearing levels, vibration sense, deep tendon reflexes, and Tinetti gait
      and balance scores in 59 normal older subjects (mean +/- SD age on entry, 78.5 +/
      3.7 years) followed up at yearly examinations (range, 8-10 years). White matter
      hyperintensities on magnetic resonance imaging taken in mid follow-up were graded
      qualitatively and quantitatively. RESULTS: For each variable except white matter
      hyperintensities, we calculated a normalized change per year. There was a
      significant (P<.05) age-related decrease in vestibulo-ocular reflex gain at 0.05
      and 0.20 Hz but not at 0.80 Hz, an increase in pure-tone hearing thresholds (at
      1, 2, 4, and 8 kHz), a decrease in vibration sense and deep tendon reflexes in
      the feet, and a decrease in total Tinetti score. However, only changes in
      vibration sense in the feet and hearing at 1 kHz were significantly correlated
      (Spearman rank correlation) with the change in Tinetti score. White matter
      hyperintensities on magnetic resonance imaging had a higher correlation with the
      yearly change in Tinetti scores. CONCLUSIONS: This longitudinal study showed age
      related decreases in vestibular, visual, auditory, and somatosensation in normal
      older people, but these changes were only weakly correlated with changes in gait
      and balance. White matter hyperintensities on magnetic resonance imaging were
      more highly correlated with changes in gait and balance, but all variables
      together accounted for only about 29% of the measured change in gait and balance.

PMID- 12810489
TI  - Analysis of outcome in retrieved dropout patients in a rivastigmine vs placebo,
      26-week, Alzheimer disease trial.
AB  - BACKGROUND: Treatment with cholinesterase inhibitors improves cognition in
      patients with Alzheimer disease (AD). In studies designed with a washout period
      at the end of the study, after treatment with a cholinesterase inhibitor is
      discontinued, the cognitive benefits of therapy are no longer apparent following
      washout. The rivastigmine trials discussed in this article were not designed with
      a posttreatment washout period at the end of the study. Therefore, to evaluate
      the effect of discontinuing treatment, we analyzed the retrieved dropout (RDO)
      population. OBJECTIVE: To evaluate the change in cognition (at week 26 vs
      baseline) observed in patients from 3 large clinical trials of AD who prematurely
      discontinued treatment with placebo or rivastigmine. DESIGN AND METHODS: Eligible
      patients with AD (Mini-Mental State Examination [MMSE] score, 10-26, inclusive)
      were enrolled in 1 of three 26-week, double-blind, placebo-controlled studies
      (Novartis US Pivotal [dose-range] Trial, US fixed-dose study, and a Global
      Pivotal [dose-range] Trial) that compared rivastigmine therapy with placebo.
      Patients who discontinued study participation (for any reason) (considered to be
      the RDO population) were encouraged to return for their scheduled week 26
      efficacy evaluations. Effects on cognition were assessed using the Alzheimer's
      Disease Assessment Scale-Cognitive subscale (ADAS-Cog). RESULTS: The results for
      the Novartis US Pivotal Trials and for the 3 studies combined (Novartis studies
      B352, B351, and B303) are reported. In the US pivotal trial, RDO patients in the
      6- to 12-mg/d group had been not receiving the drug (to be called "off drug") for
      102 (57.7) days (mean [SD]) compared with 68 (51.7) days in the RDO placebo
      group. In these RDO analyses, a statistically significantly greater worsening on
      the ADAS-Cog mean change score was observed in the placebo group (n = 17)
      compared with the rivastigmine 6- to 12-mg/d group (n = 33) at week 26 (MMSE
      score, -8.2 vs -3.0; P =.009). In the pooled studies, the mean (SD) number of
      days off treatment was 95 (52.0) days for the rivastigmine 6- to 12-mg/d group
      and 66 (52.7) days for the placebo group. The RDO analysis also showed a
      statistically significantly greater decline in cognitive function as measured by
      the ADAS-Cog mean change score in the placebo group (n = 38) compared with the
      rivastigmine 6- to 12-mg/d group (n = 88) at week 26 (MMSE score, -5.69 vs -2.5;
      P =.004). A significantly greater proportion of patients in the placebo group
      exhibited at least a 4-point and 7-point worsening in ADAS-Cog scores at week 26
      compared with the rivastigmine 6- to 12-mg/d group in both the Novartis US
      Pivotal Trials (P =.007, P =.009) and the pooled studies (P =.002, P =.017).
      CONCLUSIONS: After discontinuation of therapy, rivastigmine-treated patients
      exhibited less deterioration in cognitive function compared with placebo-treated
      patients. The less severe worsening of cognition after withdrawal of treatment in
      patients previously treated with rivastigmine suggests an effect on disease
      progression.

PMID- 12810490
TI  - The immune response at onset and during recovery from Borrelia burgdorferi
      meningoradiculitis.
AB  - BACKGROUND: Borrelia burgdorferi causes a wide range of neurologic syndromes. In
      Europe, acute meningoradiculitis is the most common manifestation. OBJECTIVE: To
      address the nature of the immune response during the course of B burgdorferi
      meningoradiculitis, with special respect to the early and late changes in
      cerebrospinal fluid (CSF). METHODS: Serial immunophenotyping was performed and
      cytokine measurements were obtained in the peripheral blood and CSF of 12
      European patients with definite B burgdorferi meningoradiculitis. RESULTS: Early
      during infection and before initiation of treatment, we observed high levels of
      interleukin (IL) 10, IL-6, and IL-8, and large numbers of B cells and plasma
      cells in the CSF of most patients. At the same time, we found a mainly unspecific
      intrathecal antibody synthesis. During resolution of the infection, cytokine
      levels normalized rapidly and plasma cells disappeared from the CSF. In parallel,
      the percentage of B cells in the CSF increased over several months, accompanied
      by rising levels of intrathecally produced B burgdorferi-specific antibodies.
      CONCLUSIONS: Our findings demonstrate that the early phase of B burgdorferi
      meningoradiculitis is characterized by a well-coordinated immune response
      involving specific cytokine release and plasma cell recruitment, followed by a
      long-lasting, antigen-specific B-cell response in the central nervous system.

PMID- 12810491
TI  - Frequency analysis and clinical characterization of spinocerebellar ataxia types
      1, 2, 3, 6, and 7 in Korean patients.
AB  - BACKGROUND: By genetic analysis, the CAG repeat expansion has been established in
      spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7. Despite the genetic
      differentiation of SCA, the characterization of the phenotypes of various SCAs
      has been challenging for better clinical diagnosis. OBJECTIVE: To analyze the
      frequencies and the clinical manifestations of SCA1, SCA2, SCA3, SCA6, and SCA7
      in Korean patients. PATIENTS AND METHODS: We performed genetic analysis in 253
      unrelated Korean patients with progressive cerebellar ataxia. We compared the
      frequencies, inheritance patterns, and various clinical manifestations of
      patients with genetically confirmed SCA. RESULTS: Among the 52 patients with
      expanded CAG repeat, the most frequent SCA type was SCA2, followed by SCA3, SCA6,
      SCA1, and SCA7. Nine patients (17%) had a negative family history of ataxia,
      mostly in SCA6. There were characteristic clinical features such as hypotonia and
      optic atrophy for SCA1; hyporeflexia for SCA2; nystagmus, bulging eye, and
      dystonia for SCA3; and macular degeneration for SCA7. Interestingly, 4 patients
      (1 with SCA2, 1 with SCA3, and 2 with SCA6) were misdiagnosed as having multiple
      system atrophy because of the absence of family history and the presence of
      parkinsonism and urinary incontinence. CONCLUSIONS: This study provides a
      detailed analysis of the clinical characteristics of the genetically defined CAG
      repeat SCAs in Korean patients. Although phenotypes were heterogeneous, some
      clinical features may be helpful for clinical diagnosis. However, genetic studies
      for SCA are needed despite uncertain family history or the presence of atypical
      clinical features causing misdiagnosis as atypical parkinsonism.

PMID- 12810492
TI  - Recurrent dermatomal vesicular skin lesions: a clue to diagnosis of herpes
      simplex virus 2 meningitis.

PMID- 12810493
TI  - Acute human T-lymphotropic virus type 1-associated myelopathy: a
      clinicopathologic study.
AB  - BACKGROUND: Recently, acute human T-lymphotropic virus type 1-associated
      myelopathy (HAM) was reported clinically without pathologic information. We
      report an autopsy case of acute HAM. OBJECTIVE: To report the case of a 52-year
      old man with acute-onset gait disturbance followed by rapidly progressive
      paraplegia, who died 9 months later. RESULTS: The postmortem study showed
      swelling of the thoracic spinal cord. Histologically, there was inflammation and
      vacuolation in the white matter. CONCLUSION: We propose that these pathologic
      findings, mimicking tropical spastic paraparesis, may represent the
      characteristic pathologic features of acute HAM.

PMID- 12810494
TI  - Cerebellitis in an adult with abnormal magnetic resonance imaging findings prior
      to the onset of ataxia.
AB  - BACKGROUND: Brain magnetic resonance imaging (MRI) findings during acute
      cerebellar ataxia in cases of postinfectious cerebellitis are frequently normal.
      This has resulted in the use of other imaging modalities, such as single-photon
      emission computed tomography, to aid diagnosis. OBJECTIVE: To illustrate the
      chronologic occurrence of cerebellar ataxia, abnormal findings on MRI, and
      cerebral spinal fluid pleocytosis in an adult case of postinfectious
      cerebellitis. METHODS: Case report. RESULTS: A patient with a 6-week history of
      occipital headaches and only mild tandem gait difficulty had abnormal MRI
      findings that were consistent with cerebellar inflammation. As cerebellar ataxia
      progressed in parallel with cerebral spinal fluid pleocytosis, MRI findings
      indicative of cerebellar inflammation resolved, while single-photon emission
      computed tomography showed cerebellar hyperperfusion. Recovery of neurologic
      function was accompanied by clearing of the pleocytosis and residual MRI-detected
      cerebellar atrophy. CONCLUSION: This case demonstrates that transient
      abnormalities can be detected by MRI before clinical manifestations of
      cerebellitis appear, while hyperperfusion detected by single-photon emission
      computed tomography is prolonged.

PMID- 12810495
TI  - Presenilin 1 mutation in an african american family presenting with atypical
      Alzheimer dementia.
AB  - BACKGROUND: Alzheimer disease (AD) is characterized by memory and visuospatial
      deficits with relative sparing of personality. Mutations in 3 genes (presenilin 1
      and 2 and amyloid precursor protein) are associated with presenile AD. Presenilin
      1 gene mutations have not been described in African Americans. METHODS: We
      studied an African American family with autosomal dominant rapidly progressive
      dementia and psychosis occurring early in the fifth decade of life. We performed
      neurologic evaluations, psychometrics, and neuroimaging. We sequenced the amyloid
      precursor protein gene, presenilin 1 and 2, and tau in affected and unaffected
      family members. One patient underwent a brain biopsy and subsequent autopsy.
      RESULTS: Personality change, auditory and visual hallucinations, delusions,
      memory impairment, word-finding difficulties, and subsequent rigidity, dystonia,
      myoclonus, and mutism developed in 2 brothers. Neuropsychometric testing in one
      was consistent with frontotemporal dementia or atypical AD. Neuroimaging studies
      showed diffuse cortical involvement. A clinical diagnosis of familial non
      Alzheimer dementia was made. However, results of temporal lobe biopsy in one
      revealed amyloid neuritic plaques, and autopsy results confirmed the diagnosis of
      AD. Gene sequencing revealed a presenilin 1 point mutation (M139V) cosegregating
      with the disease. A tau polymorphism in exon 7 (A178T) was found in an affected
      brother and unaffected relatives. CONCLUSIONS: We report the first documented
      presenilin mutation in African American patients presenting with early
      personality change, psychosis, and memory loss with preserved praxis. The M139V
      mutation can present differently between kindreds, with some features suggestive
      of a frontal lobe syndrome. The M139V mutation can lead to atypical AD, and
      genetic background may have a role in determining the phenotype of genetically
      defined AD.

PMID- 12810496
TI  - Dementia with Lewy bodies and the neurobehavioral decline of Mervyn Peake.
AB  - Mervyn Peake (1911-1968) was an accomplished British artist, poet, novelist, and
      playwright. He was a prolific and talented illustrator and wrote hundreds of
      poems, 4 novels, and several plays. His exceptional career was prematurely ended
      by a neurodegenerative illness variously ascribed to Alzheimer disease, Parkinson
      disease, or postencephalitic parkinsonism. However, a detailed review of
      biographical accounts produces substantial evidence in support of a probable
      diagnosis of dementia with Lewy bodies, a clinical entity remaining undiagnosed
      outside specialty dementia clinics. Peake developed signs of parkinsonism and
      insidious cognitive decline during his fifth decade. A breakdown in his writing
      style has frequently been cited as reflecting his encroaching dementia. Visual
      hallucinations are portrayed in sketches, and together with paranoid delusions
      are apparent in poetry composed during his illness. His deterioration was
      progressive and punctuated by well-described episodes of confusion and psychosis.
      His occasional preservation of insight is poignantly captured in drawings of
      figures with dunce caps or pointed heads, often with expressions of fear and
      apprehension etched with an economy of strokes. Peake spent his final years in
      various psychiatric institutions but continued to exhibit lucid intervals even
      late into his illness. His tragic deterioration remained undiagnosed at the time,
      but in retrospect, his progressive dementia with parkinsonism, visual
      hallucinations, and marked cognitive fluctuations likely represents one of the
      earliest recognized historical cases of dementia with Lewy bodies.

PMID- 12810497
TI  - Kennedy disease: avoiding misdiagnosis.

PMID- 12810498
TI  - Iatrogenic neurology: a wire in the carotid artery.

PMID- 12810499
TI  - Arnold-Chiari malformation.

PMID- 12810500
TI  - Erosive pustular dermatosis of the scalp: treatment with topical tacrolimus.

PMID- 12810501
TI  - Acute Churg-Strauss syndrome in an asthmatic patient receiving montelukast
      therapy.

PMID- 12810502
TI  - An international, randomized, double-blind, placebo-controlled phase 3 trial of
      intramuscular alefacept in patients with chronic plaque psoriasis.
AB  - BACKGROUND: Alefacept, human lymphocyte function-associated antigen
      3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of
      activated T cells, selectively targeting memory-effector (CD45RO+) T cells, which
      comprise more than 75% of T cells in psoriatic plaques. OBJECTIVE: To examine the
      efficacy and tolerability of intramuscular alefacept. DESIGN: International,
      randomized, double-blind, placebo-controlled, parallel-group trial. PATIENTS: A
      total of 507 patients with chronic plaque psoriasis. INTERVENTION: Placebo, 10 mg
      of alefacept, or 15 mg of alefacept administered once weekly for 12 weeks
      followed by 12 weeks of observation. MAIN OUTCOME MEASURE: Psoriasis Area
      Severity Index (PASI). RESULTS: Alefacept treatment was associated with dose
      related significant improvements in PASI from baseline. Throughout the study, a
      greater percentage of patients in the 15-mg group than in the placebo group
      achieved a significant reduction in PASI. Of patients in the 15-mg group who
      achieved at least 75% PASI reduction 2 weeks after the last dose, 71% maintained
      at least 50% improvement in PASI throughout the 12-week follow-up. There were no
      opportunistic infections and no cases of disease rebound. CONCLUSION:
      Intramuscular administration of alefacept was a well-tolerated and effective
      therapy for chronic plaque psoriasis and thus represents a convenient alternative
      to intravenous dosing.

PMID- 12810503
TI  - Botulinum toxin type a is a safe and effective treatment for axillary
      hyperhidrosis over 16 months: a prospective study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A (BTX-A)
      (BOTOX) over 16 months in the treatment of bilateral primary axillary
      hyperhidrosis. DESIGN: A 16-month study with initial double-blind randomization
      to 50 U of BTX-A or placebo per axilla. After 4 months, participants could
      receive up to 3 further treatments with open-label BTX-A over 12 months. SETTING:
      Fourteen dermatology or neurology clinics in Germany, Belgium, and the United
      Kingdom. PARTICIPANTS: Of 207 individuals aged between 17 and 74 years who had
      persistent bilateral primary axillary hyperhidrosis that interfered with daily
      activities, 174 (84%) completed the study. The baseline gravimetric assessment
      was a spontaneous sweat production of 50 mg or greater in each axilla prior to
      initial treatment. MAIN OUTCOME MEASURES: At week 4 after each treatment, the
      response rate of subjects who had at least a 50% reduction from baseline in
      axillary sweating, as measured by gravimetric assessment, was evaluated. Adverse
      events were spontaneously reported throughout the study, together with quality-of
      life parameters and assessment of neutralizing antibodies to BTX-A. RESULTS: Over
      the 16-month period, 356 BTX-A treatments were given to 207 subjects. After
      placebo treatment, the response rate at week 4 was 34.7%. After the first,
      second, and third treatment with BTX-A, response rates at week 4 were 96.1%,
      91.1%, and 83.3%, respectively. For subjects receiving more than 1 treatment, the
      mean duration between BTX-A treatments was approximately 7 months; however, 28%
      of subjects completed the study after only 1 BTX-A treatment. Subjects'
      satisfaction after treatments was consistently high, their quality of life
      improved, and there was a reduction in the impact of the disease on their lives.
      The safety profile of BTX-A after repeated treatments was excellent and no
      confirmed positive results for neutralizing antibodies to BTX-A occurred.
      CONCLUSION: Repeated intradermal injections of BTX-A over 16 months for treatment
      of primary axillary hyperhidrosis is safe and efficacious.

PMID- 12810504
TI  - Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate
      mofetil.
AB  - BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid
      sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the
      effectiveness of mycophenolate as adjuvant therapy in the treatment of both
      pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study.
      SETTING: University hospital. PATIENTS: The study included 42 consecutive
      patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus
      foliaceus) who had relapses during prednisone taper or had clinically significant
      adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22
      (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus,
      respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively.
      The median time to achieve complete remission was 9 months (range, 1-13 months).
      The treatment was administered for a median of 22 months, and the median follow
      up period was 22 months. Seventy-seven percent of patients had no adverse effect.
      Two patients had side effects severe enough to necessitate discontinuation of
      treatment, one because of symptomatic but reversible neutropenia and the other
      because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in
      the treatment of both pemphigus vulgaris and pemphigus foliaceus.

PMID- 12810505
TI  - Effects of cryogen spray cooling and high radiant exposures on selective vascular
      injury during laser irradiation of human skin.
AB  - BACKGROUND: Increasing radiant exposure offers a means to increase treatment
      efficacy during laser-mediated treatment of vascular lesions, such as port-wine
      stains; however, excessive radiant exposure decreases selective vascular injury
      due to increased heat generation within the epidermis and collateral damage to
      perivascular collagen. OBJECTIVE: To determine if cryogen spray cooling could be
      used to maintain selective vascular injury (ie, prevent epidermal and
      perivascular collagen damage) when using high radiant exposures (16-30 J/cm2).
      DESIGN: Observational study. SETTING: Academic hospital and research laboratory.
      PATIENTS: Twenty women with normal abdominal skin (skin phototypes I-VI).
      INTERVENTIONS: Skin was irradiated with a pulsed dye laser (wavelength = 585 nm;
      pulse duration = 1.5 milliseconds; 5-mm-diameter spot) using various radiant
      exposures (8-30 J/cm2) without and with cryogen spray cooling (50- to 300
      millisecond cryogen spurts). MAIN OUTCOME MEASURE: Hematoxylin-eosin-stained
      histologic sections from each irradiated site were examined for the degree of
      epidermal damage, maximum depth of red blood cell coagulation, and percentage of
      vessels containing perivascular collagen coagulation. RESULTS: Long cryogen spurt
      durations (>200 milliseconds) protected the epidermis in light-skinned
      individuals (skin phototypes I-IV) at the highest radiant exposure (30 J/cm2);
      however, epidermal protection could not be achieved in dark-skinned individuals
      (skin phototypes V-VI) even at the lowest radiant exposure (8 J/cm2). The red
      blood cell coagulation depth increased with increasing radiant exposure (to >2.5
      mm for skin phototypes I-IV and to approximately 1.2 mm for skin phototypes V
      VI). In addition, long cryogen spurt durations (>200 milliseconds) prevented
      perivascular collagen coagulation in all skin types. CONCLUSIONS: Cryogen spurt
      durations much longer than those currently used in therapy (>200 milliseconds)
      may be clinically useful for protecting the epidermis and perivascular tissues
      when using high radiant exposures during cutaneous laser therapies. Additional
      studies are necessary to prove clinical safety of these protocols.

PMID- 12810506
TI  - Psychological distress impairs clearance of psoriasis in patients treated with
      photochemotherapy.
AB  - OBJECTIVE: To assess whether psychological distress affects treatment outcome in
      psoriasis. DESIGN: Cohort study of patients with psoriasis receiving psoralen-UV
      A (PUVA) photochemotherapy. SETTING: Two university hospital dermatology
      departments. PATIENTS: One hundred twelve patients with chronic plaque psoriasis.
      MAIN OUTCOME MEASURES: We assessed clinical severity of psoriasis, psychological
      distress, and other potential confounders of treatment outcome such as skin
      phototype, family history of psoriasis, and alcohol intake before starting PUVA
      therapy. Clinical severity of disease and response to therapy were assessed at
      every fourth appointment. RESULTS: Pathological or high-level worry was the only
      significant (P =.01) predictor of time taken for PUVA to clear psoriasis. Event
      curves of time to clearance significantly differed between high- and low-level
      worry groups (log rank test, 6.64; df = 1; P =.01). Patients in the high-level
      worry group cleared with PUVA treatment at a rate 1.8 times slower than that of
      the low-level worry group (ExpB = 1.81; 95% confidence interval, 1.13-2.90).
      Fiftieth percentile time to clearance of psoriasis in the high- and low-level
      worry groups showed a median difference of 19 days. CONCLUSIONS: Psychological
      distress, in the form of excessive worrying, has a significant and detrimental
      affect on treatment outcome in patients with psoriasis. Patients with psoriasis
      who are classified as high-level worriers may benefit from adjunctive
      psychological intervention before and during treatment. These findings provide
      further evidence of the existence of a brain-skin axis.

PMID- 12810507
TI  - 308-nm excimer laser for the treatment of psoriasis: induration-based dosimetry.
AB  - OBJECTIVE: To determine the response of stubborn psoriatic plaques to the 308-nm
      excimer laser. DESIGN: Controlled study with a before-after design. SETTING: A
      university-based clinical research center. PATIENTS: Adult subjects with
      recalcitrant plaque psoriasis that have not responded to other therapies for at
      least 2 months. INTERVENTIONS: Selected psoriatic plaques were treated with the
      308-nm excimer laser. One lesion was left as a control. Each plaque was treated 2
      times a week, with an initial dose based solely on the induration component of
      the modified Psoriasis Area and Severity Index score for that lesion. Subsequent
      treatments were twice a week with dosage increments up to 50%, based on the
      change in induration. Four final consolidation doses were given once the
      induration score was reduced to zero. RESULTS: Eighteen subjects were treated.
      There were 4 dropouts because of various scheduling problems. In the remaining 14
      subjects, 44 plaques received a mean of 10 treatments (range, 4-14). Treatments
      were quick and well tolerated. The mean cumulative dose was 8.8 J/cm2 (range, 2.2
      22.8 J/cm2). Compared with controls, treated plaques showed significant
      improvement (P<.001). The only adverse event was a mild sunburn-like reaction in
      2 subjects after 1 treatment. CONCLUSIONS: Selective targeting of laser-generated
      308-nm excimer radiation with this convenient subblistering dosage schedule based
      on induration allows for individualized treatment plans for each plaque. Clearing
      of stubborn psoriatic lesions occurs rapidly and safely.

PMID- 12810508
TI  - The congenital lingual melanotic macule.
AB  - BACKGROUND: Circumscribed oral melanotic macules in adults are a well-defined
      entity. Congenital oral melanotic macules, however, are rare and not well
      characterized. We report 5 cases of congenital lingual melanotic lesions with
      consistent clinical and histologic features. OBSERVATIONS: Congenital lingual
      melanotic macules presented in all cases at birth, followed by proportional
      growth. Clinical findings were well-circumscribed, brown, single or multiple
      macules on the tongue, 2 to 5 mm in size, without history of bleeding,
      ulceration, or trauma. Family history was negative for similar pigmented lesions.
      A literature review showed only 2 previous clinical case reports with similar
      features. Histopathologic examination showed increased melanin pigmentation in
      the basal epidermal layer with varying degrees of overlying hyperkeratosis and
      subepidermal pigment-laden macrophages. No appreciable increase in melanocyte
      number, junctional nests of melanocytes, or cell atypia was noted. Two
      retrospective histopathology reviews mention 4 corresponding cases but report no
      clinical data. CONCLUSION: The congenital lingual melanotic macule represents a
      clinically distinct, benign, pigmented oral melanotic lesion, and may be more
      common than the literature suggests.

PMID- 12810509
TI  - Psoralen plus long-wave UV-A (PUVA) and bexarotene therapy: An effective and
      synergistic combined adjunct to therapy for patients with advanced cutaneous T
      cell lymphoma.
AB  - BACKGROUND: Multimodality biological response-modifier therapy that includes
      photopheresis, interferon, and bexarotene is the standard of care in our
      institution for advanced cutaneous T-cell lymphoma with peripheral blood
      involvement. We added psoralen plus long-wave UV-A (PUVA) to this regimen in 5
      patients with Sezary syndrome. OBSERVATIONS: All patients responded with
      decreased Sezary counts, resolution of lymphadenopathy, and clearing of skin
      disease after the addition of PUVA. Adverse effects were well tolerated and
      managed via close clinical and laboratory follow-up. CONCLUSIONS: The addition of
      PUVA to a multimodality immunomodulatory regimen in patients with Sezary syndrome
      can result in rapid and sustained remission of both skin and blood-borne disease.
      Further in vitro and in vivo studies are needed.

PMID- 12810510
TI  - Scleredema adultorum of Buschke treated with radiation.
AB  - BACKGROUND: Scleredema adultorum of Buschke is an uncommon skin condition that
      may accompany diabetes mellitus. Current therapeutic options are poor, with only
      case reports and small series supporting their use. OBSERVATION: We describe 3
      patients with severe restrictive scleredema associated with type 2 diabetes
      mellitus who responded to radiation therapy after other treatments had failed.
      Angle of shoulder abduction was used as an objective measurement of improvement,
      while the patients rated several subjective areas, including arm range of motion,
      ease of performing daily tasks, ease of breathing, and neck thickening. Objective
      improvement tended to plateau over time but remained well above baseline. The
      duration of subjective improvement was variable, lasting from a few months to the
      end of the observation time of 2 1/2 years. CONCLUSION: Though not consistently
      durable in its effect, radiation therapy appears to be a viable therapeutic
      option in extreme cases of this difficult-to-treat disease.

PMID- 12810511
TI  - Fire and ice.

PMID- 12810512
TI  - Immunobiologic agents for the treatment of psoriasis: clinical research delivers
      new hope for patients with psoriasis.

PMID- 12810513
TI  - Appraising systematic reviews and meta-analyses.

PMID- 12810515
TI  - Retiform purpura.

PMID- 12810516
TI  - A pig farmer with pruritic pink papules and plaques--quiz case.

PMID- 12810517
TI  - Multiple papules and nodules on the forearm.

PMID- 12810518
TI  - Palpable purpura in an asthmatic woman with eosinophilia.

PMID- 12810519
TI  - The significance of vascular invasion in primary melanomas of thin or
      intermediate thickness.

PMID- 12810520
TI  - You cannot use what you do not know.

PMID- 12810521
TI  - Efficacy of low-strength glycolic acid application in the treatment of melasma.

PMID- 12810522
TI  - Delivery and sequelae of total skin electron beam therapy.

PMID- 12810523
TI  - Topical tacrolimus is a useful adjunctive therapy for bullous pemphigoid.

PMID- 12810524
TI  - Granulomatous reaction after intradermal injections of hyaluronic acid gel.

PMID- 12810525
TI  - Identification of novel deletion Loci at 1p36 and 9p22-21 in melanocytic
      dysplastic nevi and cutaneous malignant melanomas.

PMID- 12810526
TI  - Coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell
      loss in a primate model of Parkinson's disease.
AB  - Parkinson's disease is characterized by dopamine cell loss of the substantia
      nigra. Parkinson's disease and the neurotoxin 1-methyl-4-phenyl-1,2,5,6
      tetrahydropyridine may destroy dopamine neurons through oxidative stress.
      Coenzyme Q is a cofactor of mitochondrial uncoupling proteins that enhances state
      4 respiration and eliminate superoxides. Here we report that short-term oral
      administration of coenzyme Q induces nigral mitochondrial uncoupling and prevents
      dopamine cell loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine
      administration in monkeys.

PMID- 12810527
TI  - Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient
      mice.
AB  - Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase
      responsible for the degradation of glutathione in the gamma-glutamyl cycle. This
      cycle is implicated in the metabolism of cysteine, and absence of GGT causes a
      severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice
      have multiple metabolic abnormalities and are dwarf. We show here that this
      latter phenotype is due to a decreased of the growth plate cartilage total height
      resulting from a proliferative defect of chondrocytes. In addition, analysis of
      vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia.
      Histomorphometric studies showed that this low bone mass phenotype results from
      an increased osteoclast number and activity as well as from a marked decrease in
      osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor
      chondrocytes express GGT, suggesting that the observed defects are secondary to
      other abnormalities. N-acetylcysteine supplementation has been shown to reverse
      the metabolic abnormalities of the GGT-/- mice and in particular to restore the
      level of IGF-1 and sex steroids in these mice. Consistent with these previous
      observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their
      skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic
      function. In contrast, resorbtion parameters are only partially normalized in GGT
      /- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast
      biology at least partly independently of these hormones. These results establish
      the importance of cysteine metabolism for the regulation of bone remodeling and
      longitudinal growth.

PMID- 12810528
TI  - Meal-related ghrelin suppression requires postgastric feedback.
AB  - Plasma ghrelin levels are rapidly suppressed by ingestion or gastric delivery of
      nutrients. Given that the majority of circulating ghrelin appears to be of
      gastric origin, we addressed the contribution of gastric distention or nutrient
      sensitivity to this response. Awake, unrestrained rats received intragastric
      infusions of glucose or water (1 ml/min for 12 min) with gastric emptying either
      proceeding normally or prevented by inflation of a pyloric cuff. When emptying
      was permitted, glucose infusion reduced ghrelin level by approximately 50%, and,
      in agreement with previous data, water infusions were without effect. Ghrelin
      level was not affected by either infusate when gastric emptying was prevented,
      thereby discounting a role for gastric distention in the meal-related ghrelin
      response. That glucose and water infusions were similarly ineffective when the
      pylorus was occluded shows, further, that gastric chemosensation is not a
      sufficient trigger for the ghrelin response. We conclude that the meal-related
      suppression of plasma ghrelin requires postgastric (pre- or postabsorptive)
      stimulation.

PMID- 12810529
TI  - Gonadotropin-releasing hormone stimulation of gonadotropin subunit transcription:
      evidence for the involvement of calcium/calmodulin-dependent kinase II (Ca/CAMK
      II) activation in rat pituitaries.
AB  - The intracellular pathways mediating GnRH regulation of gonadotropin subunit
      transcription remain to be fully characterized, and the present study examined
      whether calcium/calmodulin-dependent kinase II (Ca/CAMK II) plays a role in the
      rat pituitary. Preliminary studies demonstrated that a single pulse of GnRH given
      to adult rats stimulated a transient 2.5-fold rise in Ca/CAMK II activity (as
      determined by an increase in Ca/CAMK II phosphorylation), with peak values at 5
      min, returning to basal 45 min after the pulse. Further studies examined the
      alpha, LHbeta, and FSHbeta transcriptional responses to GnRH or Bay K 8644+KCl
      (BK+KCl) pulses in vitro in the absence or presence of the Ca/CAMK II-specific
      inhibitor, KN-93. Gonadotropin subunit transcription was assessed by measuring
      primary transcripts (PTs) by quantitative RT-PCR. In time-course studies, both
      GnRH and BK+KCl pulses given alone increased all three subunit PTs after 6 h (2-
      to 4-fold). PT responses to GnRH increased over time (3- to 8-fold over basal at
      24 h), although BK+KCl was ineffective after 24 h. KN-93 reduced the LHbeta and
      FSHbeta transcriptional responses to GnRH by 50-60% and completely suppressed the
      alphaPT response. In contrast, KN-93 showed no inhibitory effects on basal
      transcriptional activity or LH or FSH secretion. In fact, KN-93 tended to
      increase basal alpha, LHbeta, and FSHbeta PT levels and enhance LH secretory
      responses to GnRH. These results reveal that Ca/CAMK II plays a central role in
      the transmission of pulsatile GnRH signals from the plasma membrane to the rat
      alpha, LHbeta, and FSHbeta subunit genes.

PMID- 12810530
TI  - Glucocorticoids and sex-dependent development of brain glucocorticoid and
      mineralocorticoid receptors.
AB  - We have previously shown that repeated antenatal synthetic glucocorticoid
      exposure has sex-specific effects on hypothalamic-pituitary-adrenal development
      in the fetal and adult guinea pig. However, little is known about the mechanisms
      that underlie these sex-specific outcomes. In the current study we demonstrated
      that glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) exhibit
      sex differences in their temporal and spatial expression during fetal and early
      postnatal life. During development, we observed decreased GR mRNA in the
      paraventricular nucleus, decreased MR mRNA and MR protein in the hippocampus, and
      increased GR mRNA and GR protein in the hippocampus. We have also shown that on
      gestational d 50, maternally administered betamethasone (BETA) reduces fetal
      plasma ACTH and cortisol concentrations. BETA significantly affected hippocampal
      MR protein expression, and this effect was greatest in males. BETA was unable to
      autoregulate GR protein during fetal life, indicating that regulation of brain
      corticosteroid receptors is fundamentally different in fetal compared with adult
      life. The sex differences in the pattern of GR and MR expression during
      development may indicate different windows of vulnerability to prenatal
      glucocorticoid exposure in fetal life.

PMID- 12810531
TI  - Molecular mechanism of progesterone-induced antiproliferation in rat aortic
      smooth muscle cells.
AB  - Previously we demonstrated that progesterone at physiologic levels dose
      dependently inhibited cell proliferation in cultured rat aortic smooth muscle
      cells (RASMCs). However, the molecular mechanism underlying of progesterone
      induced antiproliferation was not clear. Here we demonstrated that progesterone
      induced a reduction of the [(3)H]thymidine incorporation into RASMCs during the S
      phase of the cell cycle. Western blotting analysis revealed that the protein
      levels of cyclin A, cyclin E, and cyclin-dependent-kinase (CDK) 2 but not cyclin
      D1 and CDK4 decreased after progesterone treatment, but those of CDK-inhibitory
      proteins, p21 and p27, increased. Immunoprecipitation showed that the formations
      of the CDK2-p21 and CDK2-p27 complex were increased and the assayable CDK2 kinase
      activity was decreased in the progesterone-treated RASMCs. In contrast, the
      formations of the CDK4-p21 and CDK4-p27 complex and the assayable CDK4 kinase
      activity were not changed significantly by progesterone treatment. Pretreatment
      of RASMCs with a p21 or p27 antisense oligonucleotide reduced the progesterone
      induced inhibition of [(3)H]thymidine incorporation into RASMCs. In conclusion,
      these data suggest that progesterone inhibits RASMCs proliferation by increasing
      the levels of p21 and p27 protein, which in turn inhibit CDK2 kinase activity,
      and finally interrupt the cell cycle.

PMID- 12810532
TI  - Centrally administered tuberoinfundibular peptide of 39 residues inhibits
      arginine vasopressin release in conscious rats.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) is a recently discovered
      neuropeptide identified on the basis of its ability to activate the PTH2
      receptor, and it is thought to be the brain PTH2 receptor's endogenous ligand.
      The PTH2 receptor is highly expressed in the hypothalamus, suggesting a role in
      the modulation of neuroendocrinological functions. PTHrP, which also belongs to
      the PTH-related peptides family, stimulates arginine vasopressin (AVP) release.
      In the present study, therefore, we investigated the effect of centrally
      administered TIP39 on AVP release in conscious rats. Intracerebroventricular
      administration of TIP39 (10-500 pmol/rat) significantly suppressed the plasma AVP
      concentration in dehydrated rats, and the maximum effect was obtained 5 min after
      administration (dehydration with 100 pmol/rat TIP39, 4.32 +/- 1.17 pg/ml; vs.
      control, 8.21 +/- 0.70 pg/ml). The plasma AVP increase in response to either
      hyperosmolality [ip injection of hypertonic saline (HS), 600 mosmol/kg] or
      hypovolemia [ip injection of polyethylene glycol (PEG)] was also significantly
      attenuated by an intracerebroventricular injection of TIP39 (HS with 100 pmol/rat
      TIP39, 2.65 +/- 0.52 pg/ml; vs. HS alone, 4.69 +/- 0.80 pg/ml; PEG with 100
      pmol/rat TIP39, 4.10 +/- 0.79 pg/ml; vs. PEG alone, 6.19 +/- 0.34 pg/ml).
      Treatment with naloxone [1.5 mg/rat, sc injection], a nonselective opioid
      receptor antagonist, significantly reversed the inhibitory effects of TIP39 on
      AVP release. These results suggest that central TIP39 plays an inhibitory role in
      the osmoregulation and baroregulation of AVP release and that intrinsic opioid
      systems are involved in its mechanism.

PMID- 12810533
TI  - Amino- and carboxyl-terminal fragments of insulin-like growth factor (IGF)
      binding protein-3 cooperate to bind IGFs with high affinity and inhibit IGF
      receptor interactions.
AB  - Both the amino-terminal and carboxyl-terminal domains of IGF binding protein
      (IGFBP)-3 are believed to contribute to high-affinity IGF binding. To investigate
      cooperativity in IGF binding by these domains, we expressed IGFBP-3 fragments 1
      88 (NBP-3) and 185-264 (CBP-3) as FLAG and hexahistidine-tagged fusion proteins,
      respectively. IGF-I and IGF-II bound to NBP-3 poorly and to CBP-3 with moderate
      affinities, approximately 1 liter/nmol. Coincubating the fragments in equimolar
      concentrations caused a significant cooperative increase in IGF binding,
      demonstrated by immunoprecipitation with IGFBP-3, FLAG, or hexahistidine
      antibodies. Equimolar NBP-3 + CBP-3 bound IGF-II with an affinity (12.2
      liter/nmol) only 4-fold lower than that of the IGFBP-3-IGF-II complex and IGF-I
      with an affinity (3.2 liter/nmol) 13-fold lower than IGFBP-3-IGF-I.
      Heterotrimeric complexes of NBP-3, CBP-3, and IGF, also demonstrated by affinity
      labeling, bound acid-labile subunit poorly. Coprecipitation assays with iodinated
      NBP-3 or CBP-3 indicated that the fragments cannot interact unless IGF is also
      present. Complexing with NBP-3 + CBP-3 inhibited IGF stimulation of type 1 IGF
      receptor activity and IGF-II binding to the type II receptor. This study
      demonstrates that isolated amino-terminal and carboxyl-terminal domains of IGFBP
      3 cooperate in the presence of IGFs to form high-affinity complexes that retain
      the ability to block IGF activity.

PMID- 12810534
TI  - Structural and functional evidence for the interaction of insulin-like growth
      factors (IGFs) and IGF binding proteins with vitronectin.
AB  - Previous studies demonstrated that IGF-II binds directly to vitronectin (VN),
      whereas IGF-I binds poorly. However, binding of VN to integrins has been
      demonstrated to be essential for a range of IGF-I-stimulated biological effects,
      including IGF binding protein (IGFBP)-5 production, IGF type-1 receptor
      autophosphorylation, and cell migration. Thus, we hypothesized that a link
      between IGF-I and VN must occur and may be mediated through IGFBPs. This was
      tested using competitive binding assays with VN and (125)iodine-labeled IGFs in
      the absence and presence of IGFBPs. IGFBP-4, IGFBP-5, and nonglycosylated IGFBP-3
      were shown to significantly enhance binding of IGF-I to VN, whereas IGFBP-2 and
      glycosylated IGFBP-3 had a smaller effect. Furthermore, binding studies with
      analogs indicate that glycosylation status and the heparin-binding domain of
      IGFBP-3 are important in this interaction. To examine the functional significance
      of IGFs binding to VN, cell migration in MCF7 cells was measured and found to be
      enhanced when VN was prebound to IGF-I in the presence of IGFBP-5. The effect
      required IGF:IGFBP:VN complex formation; this was demonstrated by use of a non
      IGFBP-binding IGF-I analog. Together, these data indicate the importance of
      IGFBPs in modulating IGF-I binding to VN and that this binding has functional
      consequences in cells.

PMID- 12810535
TI  - Neuropeptide W acts in brain to control prolactin, corticosterone, and growth
      hormone release.
AB  - The endogenous, peptide ligand for the orphan receptors GPR7 and GPR8 was
      identified to be neuropeptide W (NPW). Because these receptors are expressed in
      brain and in particular in hypothalamus, we hypothesized that NPW might interact
      with neuroendocrine systems that control hormone release from the anterior
      pituitary gland. No significant effects of NPW were observed on the in vitro
      releases of prolactin (PRL), ACTH, or GH when log molar concentrations ranging
      from 1 pM to 100 nM NPW were incubated with dispersed anterior pituitary cells.
      However, NPW, when injected into the lateral cerebroventricle of conscious,
      unrestrained male rats, in a dose-related fashion elevated PRL and corticosterone
      and lowered GH levels in circulation. The threshold dose for all three effects
      was 1.0 nmol. We conclude that endogenous NPW may play a regulatory role in the
      organization of neuroendocrine signals accessing the anterior pituitary gland but
      does not itself act as a true releasing or inhibiting factor in the gland.
      Central administration of NPW23 also stimulated water drinking and food intake.
      The ability of exogenous peptide to decrease GH but stimulate PRL secretion and
      activate the hypothalamo-pituitary adrenal axis, together with the observed
      behavioral effects, suggests that endogenous NPW may play a role in the
      hypothalamic response to stress.

PMID- 12810536
TI  - Valproic acid increases the stimulatory effect of estrogens on proliferation of
      human endometrial adenocarcinoma cells.
AB  - Long-term use of valproic acid (VA), a well-tolerated anticonvulsant agent widely
      used for treating epilepsia, has been recently shown to inhibit histone
      deacetylases, which in turn are involved in the regulation of the expression of
      estrogen receptor alpha (ERalpha) by suppressing gene transcription. Because
      estrogens are known to increase cell proliferation of human endometrial tumors,
      in this study we investigated whether treatment with VA may increase the
      proliferative response of human endometrial adenocarcinoma cells to 17-beta
      estradiol through induction of ERalpha. The results clearly show that VA, at
      concentrations of clinical interest, significantly enhanced the proliferative
      activity exerted by 17-beta-estradiol in the endometrial adenocarcinoma Ishikawa
      cell line. Moreover, in these cells treatment with VA resulted in increased
      ERalpha gene expression. Similar effects of VA on cell proliferation were also
      observed in an ERalpha-positive breast cancer cell line (MCF-7). These findings
      indicate that VA might favor proliferation of estrogen-dependent human tumors.

PMID- 12810537
TI  - Expression of functional estrogen receptor beta in locus coeruleus-derived Cath.a
      cells.
AB  - Estrogen may have an important role in the brain beyond the development and
      regulation of reproductive function. Gender differences in the incidence of
      depression suggest that regulation of mood represents one such action. The locus
      coeruleus, a brain stem noradrenergic nucleus implicated in mood regulation,
      concentrates [(3)H]estradiol, but expression of the two estrogen receptor (ER)
      subtypes (ERalpha and ERbeta) varies across species. Further, the role of each
      subtype in estrogen action on noradrenergic neurons is unknown. We examined the
      expression of ERs in the Cath.a (central-adrenergic-tyrosine-hydroxylase
      expressing) cell line derived from mouse brain stem and found that they express
      ERbeta protein but not ERalpha protein. Transient transfection assays using an
      estrogen-responsive reporter gene indicate that ERbeta is functional. The pure
      estrogen antagonist ICI 182,780 completely abolished estrogen's effects.
      Selective ER modulator results suggest that ER in Cath.a cells behaves in a
      manner consistent with ERbeta pharmacology. R,R-Tetrahydrochrysene, an ERalpha
      agonist, had no effect on luciferase-driven activity in Cath.a cells. This study
      provides the first report of a cell line that spontaneously expresses functional
      ERbeta protein. Cath.a cells may prove to be a useful tool in elucidating basic
      pharmacologic properties of ERbeta. It may also help reveal the molecular
      mechanisms involved in mood regulation by estrogen.

PMID- 12810538
TI  - Rapid enhancement of visual and place memory by estrogens in rats.
AB  - Estrogenic effects on visual (object recognition) and place (object placement)
      memory were investigated. Ovariectomized (OVX) rats received acute sc injections
      30 min before a sample trial (viewing objects), and 4 h later a
      recognition/retention trial was performed. During recognition/retention trials,
      discrimination between sample (old) and new objects (visual memory) or between
      objects in sample (old) and new locations (place memory) was tested. Subjects
      given 17alpha- or 17beta-estradiol or diethylstilbestrol (DES) 30 min before
      sample trials discriminated between objects or locations during
      recognition/retention trials whereas vehicle-treated, OVX rats did not. Estrogens
      were given a postsample trial to investigate whether enhancements were due to
      effects on memory processes or psychological/performance parameters. Hormones
      were given immediately after or 2 h after sample trials (delayed injections), and
      recognition/retention were tested 4 h after the sample trial. Both object and
      place discriminations were enhanced when estrogens were given immediately after
      sample trials, but not when injections were delayed. These results provide
      evidence that estrogen rapidly enhances visual and place memory. Moreover,
      posttraining injections suggest effects on mnemonic processes, consolidation, or
      encoding, not on performance parameters. Place memory enhancements required
      higher estrogen doses, both pre- and postsample trial. The rapid time course,
      stereospecificity of responses (alpha- and beta-estradiol are effective), and
      efficacy of various estrogens suggest interactions at other than classic estrogen
      alpha- or beta-receptors in mediating the effects. Thus, these results provide
      the first demonstration of rapid memory enhancements by estrogen and implicate
      nongenomic mechanisms, possibly an extranuclear receptor(s), in mediating the
      response.

PMID- 12810539
TI  - Regulation of the intronic promoter of rat estrogen receptor alpha gene,
      responsible for truncated estrogen receptor product-1 expression.
AB  - We have characterized the intronic promoter of the rat estrogen receptor (ER)
      alpha gene, responsible for the lactotrope-specific truncated ER product (TERP)-1
      isoform expression. Transcriptional regulation was investigated by transient
      transfections using 5'-deletion constructs. TERP promoter constructs were highly
      active in MMQ cells, a pure lactotrope cell line, whereas a low basal activity
      was detected in alphaT3-1 gonadotrope cells or in COS-7 monkey kidney cells.
      Serial deletion analysis revealed that 1) a minimal -693-bp region encompassing
      the TATA box is sufficient to allow lactotrope-specific expression; 2) the
      promoter contains strong positive cis-acting elements both in the distal and
      proximal regions, and 3) the region spanning the -1698/-1194 region includes
      repressor elements. Transient transfection studies, EMSAs, and gel shifts
      demonstrated that estrogen activates the TERP promoter via an estrogen-responsive
      element (ERE1) located within the proximal region. Mutation of ERE1 site
      completely abolishes the estradiol-dependent transcription, indicating that ERE1
      site is sufficient to confer estrogen responsiveness to TERP promoter. In
      addition, ERalpha action was synergized by transfection of the pituitary-specific
      factor Pit-1. EMSAs showed that a single Pit-1 DNA binding element in the
      vicinity of the TATA box is sufficient to confer response by the TERP promoter.
      In conclusion, we demonstrated, for the first time, that TERP promoter regulation
      involves ERE and Pit-1 cis-elements and corresponding trans-acting factors, which
      could play a role in the physiological changes that occur in TERP-1 transcription
      in lactotrope cells.

PMID- 12810540
TI  - Cytokine-induced lymphocyte chemoattraction from cultured human thyrocytes:
      evidence for interleukin-16 and regulated upon activation, normal T cell
      expressed, and secreted expression.
AB  - Mediators of lymphocyte infiltration in inflammatory thyroid disease have yet to
      be identified. Here we examine the ability of IL-1beta to enhance the production
      of chemoattractants by human thyrocytes. Primary cultures, when treated with the
      cytokine, release T lymphocyte chemotactic activity. The effect of IL-1beta is
      time dependent, and the chemoattraction activity can be partially attenuated by
      the addition of either anti-IL-16 or anti-regulated upon activation, normal T
      cell expressed, and secreted (RANTES) neutralizing antibodies. IL-16 is a CD4(+)
      specific ligand, and RANTES is a C-C type chemokine that targets monocytes and
      lymphocytes. These chemoattractants could be detected by specific ELISAs in
      conditioned medium from IL-1beta treated thyrocytes. Northern analysis revealed
      that thyrocytes express high constitutive levels of IL-16 mRNA, which were
      invariant with regard to IL-1beta (10 ng/ml) or glucocorticoid treatment. RANTES
      mRNA was not detected in control cultures but was strongly induced by the
      cytokine. IL-16 but not RANTES expression was dependent on the activity of
      caspase-3. Pro-IL-16 protein could be detected in homogenates of thyroid tissue
      from patients with multinodular goiter and Graves' disease. Thus, human
      thyrocytes, through the expression of chemoattractants, may participate in the
      recruitment of lymphocytes to the thyroid in inflammatory states.

PMID- 12810541
TI  - Hyperleptinemia precipitates diet-induced obesity in transgenic mice
      overexpressing leptin.
AB  - Transgenic mice overexpressing leptin backcrossed to the C57BL/6J genetic
      background (LepTg) have a lean phenotype, characterized by a 95% reduction in
      adipose mass; reduced plasma levels of glucose, triglycerides, insulin, and IGF
      1; and a 75% decrease in adipocyte size. High-fat diet treatment for 20 wk
      revealed that, compared with normal mice, the LepTg mice had an increased
      susceptibility to diet-induced obesity, as demonstrated by their rate of weight
      gain, higher accumulation of sc white adipose tissue mass, hypertrophy of
      adipocytes, and normalization of their reduced metabolic parameters. The stromal
      vascular fraction of white adipose tissue from the LepTg mice was highly cellular
      and contained cells capable of rapid lipid accumulation in primary cultures. The
      precipitous diet-induced obesity of the LepTg mice was accompanied with 10-fold
      and 1.6-fold elevations in insulin and IGF-1, respectively, suggesting that the
      trophic action of insulin and IGF-1 on the preadipocytes and small adipocytes may
      have caused them to rapidly differentiate and accumulate triacylglycerol stores.
      Other contributing factors may involve a shift in insulin sensitivity triggered
      by hyperleptinemia and a decrease in energy expenditure. These studies
      demonstrate that a chronic response to hyperleptinemia as in the LepTg mice is a
      predisposing factor to diet-induced obesity and suggest that individuals who are
      particularly lean because of increased leptin secretion may develop rapid obesity
      under conditions of a high-fat diet.

PMID- 12810542
TI  - Expression profiling of endometrium from women with endometriosis reveals
      candidate genes for disease-based implantation failure and infertility.
AB  - Endometriosis is clinically associated with pelvic pain and infertility, with
      implantation failure strongly suggested as an underlying cause for the observed
      infertility. Eutopic endometrium of women with endometriosis provides a unique
      experimental paradigm for investigation into molecular mechanisms of reproductive
      dysfunction and an opportunity to identify specific markers for this disease. We
      applied paralleled gene expression profiling using high-density oligonucleotide
      microarrays to investigate differentially regulated genes in endometrium from
      women with vs. without endometriosis. Fifteen endometrial biopsy samples
      (obtained during the window of implantation from eight subjects with and seven
      subjects without endometriosis) were processed for expression profiling on
      Affymetrix Hu95A microarrays. Data analysis was conducted with GeneChip Analysis
      Suite, version 4.01, and GeneSpring version 4.0.4. Nonparametric testing was
      applied, using a P value of 0.05, to assess statistical significance. Of the
      12,686 genes analyzed, 91 genes were significantly increased more than 2-fold in
      their expression, and 115 genes were decreased more than 2-fold. Unsupervised
      clustering demonstrated down-regulation of several known cell adhesion molecules,
      endometrial epithelial secreted proteins, and proteins not previously known to be
      involved in the pathogenesis of endometriosis, as well as up-regulated genes.
      Selected dysregulated genes were randomly chosen and validated with RT-PCR and/or
      Northern/dot-blot analyses, and confirmed up-regulation of collagen alpha2 type
      I, 2.6-fold; bile salt export pump, 2.0-fold; and down-regulation of N
      acetylglucosamine-6-O-sulfotransferase (important in synthesis of L-selectin
      ligands), 1.7-fold; glycodelin, 51.5-fold; integrin alpha2, 1.8-fold; and B61
      (Ephrin A1), 4.5-fold. Two-way overlapping layer analysis used to compare
      endometrial genes in the window of implantation from women with and without
      endometriosis further identified three unique groups of target genes, which
      differ with respect to the implantation window and the presence of disease. Group
      1 target genes are up-regulated during the normal window of implantation but
      significantly decreased in women with endometriosis: IL-15, proline-rich protein,
      B61, Dickkopf-1, glycodelin, N-acetylglucosamine-6-O-sulfotransferase, G0S2
      protein, and purine nucleoside phosphorylase. Group 2 genes are normally down
      regulated during the window of implantation but are significantly increased with
      endometriosis: semaphorin E, neuronal olfactomedin-related endoplasmic reticulum
      localized protein mRNA and Sam68-like phosphotyrosine protein alpha. Group 3
      consists of a single gene, neuronal pentraxin II, normally down-regulated during
      the window of implantation and further decreased in endometrium from women with
      endometriosis. The data support dysregulation of select genes leading to an
      inhospitable environment for implantation, including genes involved in embryonic
      attachment, embryo toxicity, immune dysfunction, and apoptotic responses, as well
      as genes likely contributing to the pathogenesis of endometriosis, including
      aromatase, progesterone receptor, angiogenic factors, and others. Identification
      and validation of selected genes and their functions will contribute to
      uncovering previously unknown mechanism(s) underlying implantation failure in
      women with endometriosis and infertility, mechanisms underlying the pathogenesis
      of endometriosis and providing potential new targets for diagnostic screening and
      intervention.

PMID- 12810543
TI  - Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits
      steroidogenic acute regulatory (StAR) protein and steroidogenesis.
AB  - Reactive oxygen species (ROS) are involved in a variety of pathophysiological
      conditions of the testis, and oxidative stress is known to inhibit ovarian and
      testicular steroidogenesis. The site of ROS-mediated inhibition of
      steroidogenesis in the corpus luteum and MA-10 tumor Leydig cells was shown to be
      the hormone-sensitive mitochondrial cholesterol transfer step. The purpose of
      this study was to examine the effects of ROS on steroidogenic acute regulatory
      (StAR) protein in MA-10 cells and determine the extent to which MA-10 cell
      mitochondria are sensitive to oxidative stress. cAMP-stimulated progesterone
      production was inhibited in a dose-dependent manner in MA-10 cells exposed to
      H(2)O(2). StAR protein, but not mRNA levels, was decreased in parallel to changes
      in progesterone production. Even at the highest concentrations of H(2)O(2)
      tested, there was no effect on P450 side-chain cleavage enzyme protein levels.
      Oxidative stress from exposure to exogenous xanthine oxidase and xanthine
      resulted in the inhibition of both progesterone production and StAR protein
      expression. The mature 30- and 32-kDa intramitochondrial forms of StAR were
      decreased relative to the 37-kDa extramitochondrial precursor form of StAR,
      indicating that the ROS-mediated inhibition of StAR protein was due, in part, to
      the inhibition of mitochondrial import and processing. Vital staining with the
      fluorescent dye tetramethylrhodamine ethyl ester was used to visualize changes in
      the mitochondrial electrochemical gradient-dependent membrane potential
      (Deltapsim). ROS caused a significant dissipation of Deltapsi(m) and time
      dependent loss of tetramethylrhodamine ethyl ester fluorescence. The inhibitory
      effects of H(2)O(2) were transient. There was no evidence for ROS-induced cell
      death, and following H(2)O(2) removal in the presence of continuous treatment
      with 8-bromo-cAMP, StAR protein levels and progesterone production were restored.
      In addition, there was no loss of cell viability following treatment with
      H(2)O(2) or xanthine/xanthine oxidase as determined by trypan blue exclusion.
      H(2)O(2) did not cause a significant decrease in total cellular ATP levels. These
      data indicate that oxidative stress-mediated perturbation of the mitochondria and
      dissipation of Deltapsi(m) results in the inhibition of StAR protein expression
      and its import, processing, and cholesterol transfer activity. These findings
      confirm earlier studies demonstrating the requirement for maintenance of an
      intact Deltapsi(m) for StAR protein function in cholesterol transport. The
      significant reduction in the 32- to 30-kDa mature forms of StAR, cessation of
      cholesterol transport, and loss of Deltapsi(m) are consistent with mitochondrial
      perturbation because of oxidative stress. This mechanism likely contributes to a
      host of pathophysiological events evident in testicular disorders such as
      infection, reperfusion injury, aging, cryptorchidism, and varicocele.

PMID- 12810544
TI  - Evidence that thyroid hormones act in the ventromedial preoptic area and the
      premammillary region of the brain to allow the termination of the breeding season
      in the ewe.
AB  - Thyroid hormones are permissive for various species to enter seasonal anestrus.
      In the ewe they act centrally to permit the onset of potent estradiol-negative
      feedback responsible for anestrus, but the specific sites of action are unknown.
      Therefore, we tested whether T(4) replacement via chronic microimplants in any of
      five brain areas could reverse the reproductive effects of thyroidectomy.
      Diffusion of (125)I-T(4) from the microimplant was largely (>98%) limited to a
      1.2-mm radius. A marked decline in LH concentration in ovariectomized, estradiol
      treated ewes was used as an index for anestrus. In experiment 1, all
      thyroidectomized (THX) ewes with microimplants in the medial preoptic area, A15
      area, and medial basal hypothalamus failed to enter anestrus; instead, LH levels
      remained elevated, similar to those in untreated THX controls. In ventromedial
      preoptic area (vmPOA)-microimplanted ewes, only the two animals with the most
      caudal microimplants entered anestrus, as did thyroid-intact controls and THX
      ewes receiving icv or sc T(4) replacement. In experiment 2, all vmPOA-treated
      ewes with similar placements to those effective in experiment 1 along with all
      ewes microimplanted in the premammillary region entered neuroendocrine anestrus.
      Thus, the premammillary region and vmPOA are brain sites in which thyroid
      hormones act to permit the onset of seasonal anestrus.

PMID- 12810545
TI  - Developmental expression of genes involved in neurosteroidogenesis: 3beta
      hydroxysteroid dehydrogenase/delta5-delta4 isomerase in the rat brain.
AB  - In the central nervous system, neurosteroids, in particular progesterone, have
      neurotrophic and neuroprotective effects. We thus decided to study the
      developmental expression of 3beta-hydroxysteroid-dehydrogenase/Delta(5)-Delta(4)
      isomerase (3betaHSD), an enzyme that converts pregnenolone to progesterone, in
      the male rat brain at 0, 7, 14, and 70 d after birth. 3betaHSD mRNA was widely
      distributed throughout the brain, as shown by in situ hybridization. At all ages,
      the same cerebral structures were labeled, but the intensity of the hybridization
      signal constantly decreased during postnatal development. As the hippocampus is
      of particular interest because of its neuronal plasticity, we chose to quantify
      the changes in 3betaHSD mRNA levels as well as progesterone and pregnenolone
      concentrations in this structure. Quantitative in situ hybridization confirmed a
      decrease in the expression of 3betaHSD mRNA with progressing age, as revealed by
      a significant reduction in the density of silver grains per cell in the CA1
      layer. This decrease was confirmed by semiquantitative RT-PCR on hippocampal
      samples. Concentrations of hippocampal pregnenolone and progesterone measured by
      gas chromatography/mass spectrometry were highest on the day of birth and lower
      at the other ages. Plasma concentrations of these steroids were lower than those
      in the hippocampus, suggesting that they may have been mostly synthesized in situ
      since the day of birth. These results demonstrate variations in the expression of
      a gene coding for an enzyme critically involved in progesterone synthesis in the
      hippocampus throughout postnatal development.

PMID- 12810546
TI  - Nitric oxide inhibits prolactin secretion in pituitary cells downstream of
      voltage-gated calcium influx.
AB  - The coupling between nitric oxide (NO)-cGMP signaling pathway and prolactin (PRL)
      release in pituitary lactotrophs has been established previously. However, the
      messenger that mediates the action of this signaling pathway on hormone secretion
      and the secretory mechanism affected, calcium dependent or independent, have not
      been identified. In cultured pituitary cells, basal PRL release was controlled by
      spontaneous voltage-gated calcium influx and was further enhanced by
      depolarization of cells and stimulation with TRH. Inhibition of constitutively
      expressed neuronal NO synthase decreased NO and cGMP levels and increased basal
      PRL release. The addition of a slowly releasable NO donor increased cGMP levels
      and inhibited basal PRL release in a time-dependent manner. Expression of
      inducible NO synthase also increased NO and cGMP levels and inhibited basal,
      depolarization-induced, and TRH-induced PRL release, whereas inhibition of this
      enzyme decreased NO and cGMP production and recovered PRL release. None of these
      treatments affected spontaneous and stimulated voltage-gated calcium influx. At
      basal NO levels, the addition of permeable cGMP analogs did not inhibit PRL
      secretion. At elevated NO levels, inhibition of cGMP production and facilitation
      of its degradation did not reverse inhibited PRL secretion. These experiments
      indicate that NO inhibits calcium-dependent PRL secretion in a cGMP-independent
      manner and downstream of voltage-gated calcium influx.

PMID- 12810547
TI  - Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and
      androgen metabolism in prostate cells.
AB  - Human aldo-keto reductases (AKRs) of the AKR1C subfamily function in vitro as 3
      keto-, 17-keto-, and 20-ketosteroid reductases or as 3alpha-, 17beta-, and
      20alpha-hydroxysteroid oxidases. These AKRs can convert potent sex hormones
      (androgens, estrogens, and progestins) into their cognate inactive metabolites or
      vice versa. By controlling local ligand concentration AKRs may regulate steroid
      hormone action at the prereceptor level. AKR1C2 is expressed in prostate, and in
      vitro it will catalyze the nicotinamide adenine dinucleotide (NAD(+))-dependent
      oxidation of 3alpha-androstanediol (3alpha-diol) to 5alpha-dihydrotestosterone
      (5alpha-DHT). This reaction is potently inhibited by reduced NAD phosphate
      (NADPH), indicating that the NAD(+): NADPH ratio in cells will determine whether
      AKR1C2 makes 5alpha-DHT. In transient COS-1-AKR1C2 and in stable PC-3-AKR1C2
      transfectants, 5alpha-DHT was reduced by AKR1C2. However, the transfected AKR1C2
      oxidase activity was insufficient to surmount the endogenous 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) activity, which eliminated 3alpha-diol
      as androsterone. PC-3 cells expressed retinol dehydrogenase/3alpha-HSD and 11-cis
      retinol dehydrogenase, but these endogenous enzymes did not oxidize 3alpha-diol
      to 5alpha-DHT. In stable LNCaP-AKR1C2 transfectants, AKR1C2 did not alter
      androgen metabolism due to a high rate of glucuronidation. In primary cultures of
      epithelial cells, high levels of AKR1C2 transcripts were detected in prostate
      cancer, but not in cells from normal prostate. Thus, in prostate cells AKR1C2
      acts as a 3-ketosteroid reductase to eliminate 5alpha-DHT and prevents activation
      of the androgen receptor. AKR1C2 does not act as an oxidase due to either potent
      product inhibition by NADPH or because it cannot surmount the oxidative 17beta
      HSD present. Neither AKR1C2, retinol dehydrogenase/3alpha-HSD nor 11-cis-retinol
      dehydrogenase is a source of 5alpha-DHT in PC-3 cells.

PMID- 12810548
TI  - Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary
      adrenal axis in adult offspring.
AB  - Reduced size at birth in humans has been associated with altered function of the
      hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life.
      Experimentally, maternal undernutrition has also been associated with altered
      fetal HPA function. However, the relationship between birth size, fetal
      nutrition, and adult pathophysiology is not clear. We recently have reported that
      glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more
      closely associated with birth weight than with nutritional insult in late
      gestation or with current weight. Here, we report adult HPA function in the same
      group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or
      20 d (UN20) from 105 d gestation (term, 146 d), or were ad libitum-fed controls.
      At 30 months, female offspring were subjected to an insulin tolerance test and a
      CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth,
      but there were no significant differences in weight at 30 months. Adult UN10 ewes
      had an increased ACTH response to both CRH+AVP challenge and insulin tolerance
      test, but no differences in cortisol response. UN10 ewes also demonstrated
      elevated 11-deoxycortisol concentrations, but lower progesterone concentrations,
      in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to
      these challenges were not different from ad libitum controls. Protein levels of
      P450(c17) and P450(11beta1) were not significantly different among groups. We
      conclude that brief maternal undernutrition for 10 d, but not 20 d, in late
      gestation alters HPA function in adult offspring. In contrast to our previous
      findings, these HPA effects are independent of birth weight and current weight,
      suggesting that different mechanisms may be involved in programming different
      physiological axes.

PMID- 12810549
TI  - Increased dietary fat attenuates the anorexic effects of intracerebroventricular
      injections of MTII.
AB  - The hypothalamic melanocortin (MC) system provides a critical inhibitory control
      on food intake and body weight. Because access to high-fat (HF) diets is
      associated with the development of obesity, we hypothesized that increased
      dietary fat attenuates signaling through the MC system. To evaluate this
      hypothesis, we compared the efficacy of the MC3/4 receptor agonist, MTII, to
      reduce food intake in rats fed carefully matched HF or low-fat (LF) diets for 12
      wk. Rats given the HF diet ad libitum were significantly more obese than rats
      given the LF diet, and had significantly higher plasma insulin and leptin levels.
      MTII given into the third cerebral ventricle in doses of 0.1, 0.3, and 1.0 nmol
      was less effective at reducing food intake in HF rats than in LF rats. Whole
      hypothalamic expression of the MC agonist precursor gene, proopiomelanocortin,
      the MC antagonist agouti-related protein, and the MC4 receptor, were not
      different between the HF and LF groups. These results indicate that consumption
      of a HF diet decreases signaling through the melanocortin system, an abnormality
      that could contribute to diet-induced obesity.

PMID- 12810550
TI  - Extracellular signal-regulated kinase 1/2 activation by myometrial oxytocin
      receptor involves Galpha(q)Gbetagamma and epidermal growth factor receptor
      tyrosine kinase activation.
AB  - The mechanisms by which oxytocin (OT) stimulates extracellular signal-regulated
      kinase 1/2 (ERK1/2) are only partially understood. OT receptor (OTR) signals
      predominantly through Galpha(q), but ERK1/2 phosphorylation (ERK1/2-P) in PHM1
      myometrial cells was not eliminated by inhibition of downstream effectors such as
      phospholipase C or protein kinase C. Inconsistent with a Galpha(i)-coupled
      response, pertussis toxin inhibition of OT-induced ERK1/2-P was reversed by the
      protein kinase A inhibitors Rp-cAMPS and KT5720. Consistent with an inhibitory
      role for protein kinase A, pertussis toxin pretreatment raised cellular cAMP and
      8-(4-chlorophenylthio)-cAMP inhibited OT-induced ERK1/2-P. Attenuation of the OT
      response by the Gbetagamma scavenger carboxyl terminus of the beta-adrenergic
      receptor kinase implicated a Gbetagamma-mediated pathway. In both COSM6 cells
      overexpressing OTR (OTR-COSM6) and in PHM1 cells, the epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor AG1478 markedly reduced OT-induced
      ERK1/2-P, whereas the platelet-derived growth factor receptor tyrosine kinase
      inhibitor AG1296 had no effect. Furthermore, OT increased EGFR tyrosine
      phosphorylation in OTR-COSM6 cells, which was inhibited by AG1478 or EGTA plus
      thapsigargin pretreatment. AG1478 did not affect inositol 1,4,5-triphosphate
      production by OT or protein kinase C-stimulated ERK1/2-P but completely blocked
      ionomycin-induced ERK1/2-P and EGFR tyrosine phosphorylation. In both OTR-COSM6
      and PHM1 cells, EGTA reduced OT-stimulated ERK1/2-P; no ERK1/2-P was observed
      when intracellular calcium increases were blocked by pretreatment with
      thapsigargin plus EGTA. These data are consistent with activation of a Gbetagamma
      mediated pathway as a consequence of Galpha(q) activation in myometrium and OTR
      COSM6 cells that results in increased ERK1/2-P. This pathway involves both EGFR
      activation and an influence of calcium.

PMID- 12810551
TI  - Gonadotropin-releasing hormone signaling pathways in an experimental ovarian
      tumor.
AB  - Previous results showed that GnRH signaling is altered in cells from rat
      luteinized ovarian tumors (tumor group) because it did not activate the
      phospholipase C pathway, in contrast to control ovarian cells from superovulated
      prepubertal rats (SPO). In the present work, alternate GnRH-induced second
      messengers such as phospholipase A(2) and phospholipase D activation, cAMP
      production, ERK1/2 phosphorylation, and the presence of G proteins were evaluated
      to determine GnRH mechanism of action in tumor cells. G proteins examined were
      present in both cell types. Buserelin, a GnRH agonist, (1, 10, and 100 ng/ml)
      increased phosphatidylethanol in SPO, indicating phospholipase D activation. Only
      100 ng/ml buserelin induced a significant response in the tumor group. Buserelin
      (100 ng/ml) increased (3)H-arachidonic acid in culture media in SPO, indicating
      phospholipase A(2) activation; no effect was observed in the tumor group.
      Buserelin (100 and 1000 ng/ml) induced pertussis toxin-insensitive cAMP increases
      in both cell types, with similar potencies. In the tumor group, buserelin (100
      ng/ml) inhibited human chorionic gonadotropin-induced cAMP and progesterone; this
      effect was protein kinase C (PKC) dependent (inhibited by GF109203X, a PKC
      inhibitor). Buserelin (100 and 1000 ng/ml) induced ERK1/2 phosphorylation in both
      cell kinds. Buserelin-induced ERK1/2 activation was G(i/0) independent and PKC
      dependent. Only in the tumor group, buserelin-induced ERK1/2 activation was cAMP
      dependent (abolished by SQ 22536, the adenylyl cyclase inhibitor). Furthermore,
      dibutyryl cAMP-induced ERK1/2 activation in the tumor group was PKC dependent
      (inhibited by GF109203X). In conclusion, activation of phospholipases in tumor
      cells does not seem to mediate GnRH effects. GnRH signaling seems to involve
      adenylyl cyclase activation, PKC stimulation, and ERK1/2 phosphorylation.

PMID- 12810552
TI  - The naturally occurring variant of estrogen receptor (ER) ERDeltaE7 suppresses
      estrogen-dependent transcriptional activation by both wild-type ERalpha and
      ERbeta.
AB  - We have isolated and functionally characterized the exon 7-skipped variant
      (ERDeltaE7) of estrogen receptor (ER)alpha, which has emerged as the predominant
      variant expressed in multiple normal and tumoral tissues. However, to date no
      function has been established for this variant in mammalian cells. ERDeltaE7
      exhibits a negligible ability to bind ligands, insensitivity to allosteric
      modulation by estrogen and antiestrogens, and loss of estrogen-dependent
      interaction with p160 coactivators such as SRC-1 and AIB1. ERDeltaE7 is able to
      form heterodimers with both ERalpha and ERbeta in a ligand-independent manner.
      Transient expression experiments in HeLa cells show that increasing amounts of
      ERDeltaE7 result in a progressive inhibition of the estrogen-dependent
      transcriptional activation by both wild-type ERalpha and ERbeta on estrogen
      response element-driven promoters. The inhibitory effect of ERDeltaE7 is due to
      the inhibition of binding of wild-type receptors to their responsive elements.
      Surprisingly, the activation function (AF)-1-dependent transactivation triggered
      by epithelial growth factor and phorbol-12-myristate-13-acetate is also abolished
      in ERDeltaE7 despite AF1 integrity, suggesting a cross-talk between AF1 and AF2
      regions of the receptor. These results indicate that the naturally occurring
      variant ERDeltaE7 is a dominant negative receptor that, when expressed at high
      levels relative to wild-type ERs, might have profound effects on several estrogen
      dependent functions.

PMID- 12810553
TI  - Proteolysis of insulin-like growth factor binding proteins -4 and -5 in bovine
      follicular fluid: implications for ovarian follicular selection and dominance.
AB  - Dominant follicles are characterized by low levels of low molecular weight IGF
      binding proteins (IGFBPs) and by proteolytic activity against IGFBP-4 and -5. To
      examine the hypothesis that proteolysis of IGFBP-4 and -5 plays a critical role
      in selection of the dominant follicle, we isolated follicles at various stages
      during the first wave of follicular development during the bovine estrous cycle,
      using ultrasonography to follow follicular growth. Ovariectomies were performed
      before divergence in follicular size (group 1; largest follicle, approximately 7
      mm in diameter), at about the expected time of size divergence (group 2; largest
      follicle, approximately 8 mm) or after a dominant follicle was clearly present
      (group 3; largest follicle, > or =9 mm). The four largest follicles (F1-F4) were
      dissected and concentrations of steroids, IGFBPs and free IGF-I and levels of
      proteolytic activity for IGFBP-4 and -5 in the follicular fluid were determined.
      Follicles in group 1 did not differ significantly in size or estradiol
      concentrations, but levels of proteolytic activity against IGFBP-4 and -5 were
      higher in F1-F2 than in F3-F4. However, in group 2 the largest follicle (F1) had
      higher estradiol, free IGF-I, and IGFBP-4 and -5 proteolytic activity than F2-F4,
      whereas only slight (dissected) or no (ultrasound) differences in diameters could
      be detected. Differences between F1 and F2-F4 in diameter, estradiol, free IGF-I,
      and IGFBP-4 and -5 proteolytic activity were even greater in group 3. In
      addition, the hormonal regulation of IGFBP-4 and -5 proteolysis was evaluated in
      vivo by injecting heifers with small doses of recombinant bovine FSH to induce
      codominant follicles (group 4). The induced codominant follicles were larger and
      had higher IGFBP-4 and -5 proteolytic activity than subordinate follicles. The
      results suggest that follicular selection is a progression of changes starting
      with acquisition of an FSH-inducible IGFBP-4/-5 proteolytic activity, leading to
      an increase in intrafollicular concentration of free IGF-I that, in turn,
      synergizes with FSH to promote greater estradiol production by the follicle
      destined for dominance.

PMID- 12810554
TI  - Cytokine-hormone interactions: tumor necrosis factor alpha impairs biologic
      activity and downstream activation signals of the insulin-like growth factor I
      receptor in myoblasts.
AB  - TNFalpha is elevated following damage to skeletal muscle. Here we provide
      evidence that TNFalpha acts on muscle cells to induce a state of IGF-I receptor
      resistance. We establish that TNFalpha inhibits IGF-I-stimulated protein
      synthesis in primary porcine myoblasts. Similar results were observed in
      C(2)C(12) murine myoblasts, where as little as 0.01 ng/ml TNFalpha significantly
      inhibits protein synthesis induced by IGF-I. TNFalpha also impairs the ability of
      IGF-I to induce expression of a key myogenic transcription factor, myogenin. The
      inhibition by TNFalpha of IGF-I-induced protein synthesis and expression of
      myogenin is not due to direct killing of myoblasts by TNFalpha. Although IGF-I
      induces an approximately 19-fold induction in tyrosine phosphorylation of the
      beta-chains of its receptor, TNFalpha does not inhibit this autophosphorylation.
      Instead, TNFalpha significantly reduces by approximately 50% IGF-I-stimulated
      tyrosine phosphorylation of two of the major downstream receptor docking
      molecules, insulin receptor substrate (IRS)-1 and IRS-2. These results establish
      that low picogram concentrations of TNFalpha acts on both porcine and murine
      myoblasts to impair tyrosine phosphorylation of both IRS-1 and IRS-2, but not the
      receptor itself. These data are consistent with the notion that very low
      physiological concentrations of TNFalpha interfere with both protein synthesis
      and muscle cell development by inducing a state of IGF-I receptor resistance.

PMID- 12810555
TI  - Obese Zucker rats have reduced mineralocorticoid receptor and 11beta
      hydroxysteroid dehydrogenase type 1 expression in hippocampus-implications for
      dysregulation of the hypothalamic-pituitary-adrenal axis in obesity.
AB  - Obese Zucker rats have elevated basal corticosterone levels and an increased
      stress response suggestive of an increased activity of the hypothalamic-pituitary
      adrenal (HPA) axis. We hypothesized that altered central expression of
      glucocorticoid receptors (GR), mineralocorticoid receptors (MR), and/or 11beta
      hydroxysteroid dehydrogenase type 1 (11betaHSD1) contribute to these changes. In
      brains from young adult male rats, in situ hybridization and Western blotting
      showed that obese rats had normal hippocampal GR mRNA and protein levels. In
      contrast, in obese rats, 11betaHSD1 mRNA levels were reduced in a subpopulation
      of hippocampal cells in the main neuronal layers (by 37-47%, P < 0.05), whereas
      11betaHSD1 levels in sparse high-expressing cells did not differ. MR mRNA was
      decreased in all regions of the hippocampus (by 37-49%, P < 0.05 for CA1-2 and P
      < 0.01 for dentate gyrus) and in frontal cortex (by 16%, P < 0.05) in obese rats.
      In whole hippocampal homogenates, however, neither the protein concentration of
      MR by Western blot nor activity of 11betaHSD1 was measurably different between
      the phenotypes. To test the functional importance of lower central MR expression,
      groups of lean and obese rats were given spironolactone before restraint stress.
      In vehicle-treated animals, obese rats had higher plasma corticosterone levels
      than lean rats after stress (by ANOVA, P < 0.05). Spironolactone markedly
      increased the corticosterone response in both groups, but the incremental rise
      was smaller in the obese rats, so that spironolactone abolished the differences
      between groups. We conclude that lower levels of MR, but not GR, contribute to
      the increased HPA activity in the obese Zucker rats and that this seems more
      influential during stress than in the basal state. This may be exacerbated by
      impaired local regeneration of corticosterone by 11betaHSD1. These abnormalities
      could contribute to the subtle changes in the HPA axis in rodent and human
      obesity.

PMID- 12810556
TI  - Overexpression of dominant negative retinoic acid receptor alpha causes alveolar
      abnormality in transgenic neonatal lungs.
AB  - To assess retinoic acid receptor (RAR) function in alveolarization and
      respiratory epithelial cell differentiation/proliferation, doxycycline (Dox)
      regulatable double-transgenic mouse lines were established, in which the dominant
      negative RARalpha was overexpressed under the control of the human surfactant
      protein-C 3.7-kb promoter or the rat Clara cell secretory protein 2.3-kb
      promoter. Overexpression of dominant negative RARalpha was induced by Dox in
      neonatal lungs from d 1-21 after birth, a critical period for alveolar
      maturation. This led to substantial alveolar abnormality with increased air
      space, larger but fewer alveoli, and the diminished alveolar surface area. In
      these animals, numbers of alveolar epithelial cells were significantly reduced
      upon Dox treatment. Expression of an RAR downstream target surfactant protein B
      gene, which is critical for maintaining the surfactant structure, was inhibited
      upon Dox treatment in alveolar type II epithelial cells. This finding supports a
      concept that endocrine molecule retinoic acid, and its receptor RARs play a
      critical role in alveolarization during the neonatal period of the lung.

PMID- 12810557
TI  - Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary
      adrenocortical axis.
AB  - We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the
      hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise
      was provided by giving mice access to a running wheel, in which they indeed ran
      for about 4 km/d. Exercising mice showed similar body weights as control animals
      but presented less abdominal fat, lighter thymuses, and heavier adrenal glands.
      Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas
      control mice had larger left than right adrenals, this condition was abolished in
      exercising animals, mainly because of enlargement of the right adrenal cortex.
      Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice
      was increased. In exercising mice, early-morning baseline plasma ACTH levels were
      decreased, whereas plasma corticosterone levels at the start of the dark phase
      were twice as high as those in control animals. To forced swimming and restraint
      stress, exercising mice responded with higher corticosterone levels than those of
      the control animals but with similar ACTH levels. However, if exposed to a novel
      environment, then exercising mice presented decreased ACTH responses.
      Interestingly, exercising mice showed a decreased corticosterone response to
      novelty only when the novel environment contained a functioning running wheel.
      Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor
      levels were decreased, in hippocampus of exercising animals. Corticotropin
      releasing factor mRNA levels in the paraventricular nucleus were lower in
      exercising mice. Thus, voluntary exercise results in complex, adaptive changes at
      various levels within the HPA axis as well as in sympathoadrenomedullary and
      limbic/neocortical afferent control mechanisms. These changes seem to underlie
      the differential responsiveness of the HPA axis to physical vs. emotional
      challenges.

PMID- 12810558
TI  - Leptin distribution and metabolism in the pregnant rat: transplacental leptin
      passage increases in late gestation but is reduced by excess glucocorticoids.
AB  - Leptin is essential for the establishment of pregnancy and appears to promote
      fetal growth, but the mechanisms regulating fetal leptin exposure remain unclear.
      In rodents, indirect evidence suggests that fetal leptin is partly derived from
      the maternal circulation via transplacental passage. Indeed, the placenta
      expresses mRNA for Ob-Ra, one of the short forms of the leptin receptor (Ob-R(S))
      important in leptin transport, and this expression increases markedly in late
      pregnancy. Therefore, we determined the transplacental passage of maternal leptin
      to the fetus in the rat and whether this transport increases near term in
      association with a rise in placental expression of Ob-R(S) protein. Because of
      the proposed role of leptin in promoting fetal growth, we also assessed the
      effect of glucocorticoid-induced fetal growth retardation on placental leptin
      transport. Anesthetized rats received a constant infusion of (125)I-leptin via a
      jugular cannula before and at d 16 and 22 of pregnancy (term = d 23); plasma
      samples were obtained at 10, 20, 40, 60, 80, and 100 min, and fetuses and
      placentas were collected at the time of the final sample. The metabolic clearance
      rate of leptin fell (P < 0.01) from 3.08 +/- 0.23 ml/min per kg in nonpregnant
      rats to 2.36 +/- 0.13 ml/min per kg by d 22. Transplacental passage of (125)I
      leptin, estimated from its concentration in the whole fetus relative to maternal
      plasma, increased 10-fold (P < 0.005) between d 16 and d 22 of pregnancy. Over
      this same period, Ob-R(S) protein expression in the placental labyrinth zone
      increased by almost 2-fold. Transplacental leptin passage was reduced (P < 0.05)
      by 77% after maternal dexamethasone treatment, whereas suppression of endogenous
      glucocorticoid synthesis (by metyrapone) increased (P < 0.05) the transfer of
      maternal leptin to the fetus by 55%. These data show that transplacental passage
      of maternal leptin is a significant source of fetal leptin and increases markedly
      during late pregnancy. Consistent with the proposed role of leptin as a fetal
      growth factor, transplacental leptin passage is reduced in association with
      glucocorticoid-induced fetal growth retardation.

PMID- 12810559
TI  - Heterogeneous expression of the potassium-chloride cotransporter KCC2 in
      gonadotropin-releasing hormone neurons of the adult mouse.
AB  - In mature central neurons, chloride extrusion mediated by the K-Cl cotransporter
      KCC2 appears to be largely responsible for the Cl(-) driving force that allows
      gamma-aminobutyric acid(A) (GABA(A)) receptor activation to trigger a
      hyperpolarization. In its absence, GABA's effect is typically depolarizing and
      often excitatory. We examined the colocalization of KCC2 and GnRH in adult male
      and female mice using a combined in situ hybridization-immunofluorescence
      procedure. We found that KCC2 was localized to approximately 34% of GnRH neurons.
      This proportion was similar in females and males. However, females exhibited a
      marked rostrocaudal gradient of colocalization that was not seen in males. By
      contrast, KCC2 was localized to nearly all vasopressin neurons of the supraoptic
      nucleus. These results indicate that a substantial fraction of GnRH neurons may
      be depolarized and excited by GABA(A) receptor activation throughout life,
      supporting the existence of functionally heterogeneous subpopulations.

PMID- 12810560
TI  - Insulin-like growth factor II allows prolonged blood glucose normalization with a
      reduced islet cell mass transplantation.
AB  - IGF-II has been reported to decrease neonatal islet cell apoptosis and in vitro
      adult islet cell necrosis and apoptosis, but the usefulness of IGF-II in a
      transplantation setting is unknown. We evaluated the effect of in vitro IGF-II
      incubations on microencapsulated rat islet survival both in vitro and in minimal
      mass transplantations into diabetic mice. After 6 d in culture, fresh
      examinations, histology, fluorescence microscopy, sodium 3'-[1-(phenyl-amino
      carbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro)-benzene sulfonic acid hydrate
      assay, and apoptosis studies all indicated that IGF-II significantly improves
      islet cell viability in a dose-dependent fashion. IGF-II 100 ng/ml and 500 ng/ml
      induced a 51% and 83% increase of viable islets (P = 0.052, P < 0.01). A 20%,
      29%, and 33% reduction of the apoptotic index was observed with 50, 100, and 500
      ng/ml incubations respectively (P < 0.05; P < 0.005; P < 0.001). Ten weeks after
      transplantation of 150 encapsulated rat islet equivalents incubated with IGF-II
      500 ng/ml, 80% of diabetic mice were normoglycemic. Without IGF-II preincubation,
      only 8% of the recipients remained normoglycemic with the transplantation of 150
      islets and 42% with 300 islets (P < 0.05). In conclusion, IGF-II promotes islet
      cell survival, and allows successful transplantation using a smaller number of
      islets.

PMID- 12810561
TI  - Inhibition of spontaneous and androgen-induced prostate growth by a
      nonhypercalcemic calcitriol analog.
AB  - We have recently found that analog V (BXL-353, a calcitriol analog) inhibits
      growth factor (GF)-stimulated human benign prostate hyperplasia (BPH) cell
      proliferation by disrupting signal transduction, reducing Bcl-2 expression, and
      inducing apoptosis. We now report that BXL-353 blocks in vitro and in vivo
      testosterone (T) activity. BPH cells responded to T and dihydrotestosterone (DHT)
      with dose-dependent growth and reduced apoptosis. Exposure of BPH cells to BXL
      353 significantly antagonized both T- and DHT-induced proliferation and induced
      apoptosis, even in the presence of T. To verify whether BXL-353 reduced prostate
      growth in vivo, we administered it orally to either intact or castrated rats,
      supplemented with T enanthate. Nonhypercalcemic doses of BXL-353 time- and dose
      dependently reduced the androgen effect on ventral prostate weight, similarly to
      finasteride. Comparable results were obtained after chronic administration of BXL
      353 to intact rats. Clusterin (an atrophy marker) gene and protein were up
      regulated by BXL-353 in rat prostate, and nuclear fragmentation was widely
      present. The antiandrogenic properties of BXL-353 did not interfere with
      pituitary and testis function, as assessed by serum determination of rat LH and
      T. BXL-353 did not compete for androgen binding to BPH homogenates and failed to
      inhibit 5alpha-reductase type 1 and type 2 activities. In conclusion, BXL-353
      blocks in vitro and in vivo androgen-stimulated prostate cell growth, probably
      acting downstream from the androgen receptor, without affecting calcemia or sex
      hormone secretion. BXL-353 and other vitamin D(3) analogs might thus represent an
      interesting class of compounds for treating patients with BPH.

PMID- 12810562
TI  - Endogenous G protein-coupled receptor kinase 6 triggers homologous beta
      adrenergic receptor desensitization in primary uterine smooth muscle cells.
AB  - We previously reported that G protein-coupled receptor kinase (GRK) may
      contribute to beta-adrenergic receptor (beta-AR) uncoupling occurring just before
      parturition in rat uterine muscle (myometrium). To identify the GRK involved, we
      set up in this study a primary cell culture retaining the morphological and
      functional characteristics of myometrial tissue as well as the in vivo pattern of
      GRK expression (GRK2, GRK5, and GRK6). In this model, homologous beta-AR
      desensitization was assessed by an approximately 60% decrease in cAMP production
      to a subsequent challenge with the beta-agonist, isoproterenol. Desensitization
      was reduced by 36% with a GRK inhibitor, heparin, and by 31% with a protein
      kinase A in-hibitor, H89. Using antibodies known to specifically inhibit either
      GRK2/3 or GRK4-6 families, we demonstrated that only the GRK4-6 family mediated
      beta-AR desensitization. To discriminate between endogenous GRK5 and GRK6, we
      attempted to inhibit their action by introducing, into myometrial cells, kinase
      dead dominant-negative mutants ((K215R)GRK5 and (K215R)GRK6). Expression of
      (K215R)GRK6 increased by approximately 70% the cAMP response to isoproterenol
      without effect on forskolin stimulation. Conversely, expression of (K215R)GRK5 or
      (K220R)GRK2 had no effect on beta-adrenergic signaling. These results strongly
      suggest that endogenous GRK6 mediate homologous beta-AR desensitization in
      myometrial cells.

PMID- 12810563
TI  - A testicular influence on restraint-induced activation of medial parvocellular
      neurons in the paraventricular nucleus in the male rat.
AB  - To gauge the strength by which the testes influence stress-induced activation of
      neurosecretory neurons in the paraventricular nucleus, we studied within medial
      parvocellular neurons the effects of gonadectomy on restraint-induced Fos
      immunoreactivity and on CRH and arginine vasopressin (AVP) heteronuclear (hn) RNA
      expression levels. Relative to intact male rats (sham-gonadectomized),
      gonadectomized rats showed a significantly greater number of medial parvocellular
      neurons recruited to express Fos protein evident at 0.5 h and from 1-4 h after
      the onset of 30-min restraint exposure. Restraint provoked a transient increase
      in hnCRH levels that was maximal at the end of restraint and this was significant
      only in gonadectomized rats. Both intact and gonadectomized rats displayed an
      increase in AVP hnRNA expression levels in response to restraint exposure;
      however, it was significantly greater in gonadectomized rats. All of these
      responses were accompanied by a higher corticosterone response in gonadectomized
      compared with intact rats and negatively correlated with plasma testosterone
      concentrations, with the exception of stress-induced CRH transcription. These
      findings indicate an inhibitory role for testosterone on stress-induced indexes
      of synaptic (Fos) and transcriptional (AVP hnRNA) activation among
      hypophysiotropic paraventricular neurons and provide meaningful end points with
      which to pursue how and where androgens operate on stress-related input to the
      paraventricular nucleus motor neurons.

PMID- 12810564
TI  - Molecular cloning and characterization of bovine prostaglandin E2 receptors EP2
      and EP4: expression and regulation in endometrium and myometrium during the
      estrous cycle and early pregnancy.
AB  - Prostaglandins (PGs) play important functions in the reproductive system, and
      PGE(2) appears necessary for recognition of pregnancy. We have found that PGE(2)
      is able to increase cAMP generation in the bovine endometrium. There are two
      PGE(2) receptors (EP), EP2 and EP4, that are coupled to adenylate cyclase to
      generate cAMP, but these receptors have not been studied in the bovine. We have
      cloned and characterized bovine EP2 and EP4 receptors and studied their
      expression in the uterus. The amino acid sequences of bovine EP2 and EP4 possess
      a high degree (>80%) of identity with the other mammalian homologs. EP2 is
      expressed in most tissues, and EP4 is expressed only in intestine and testis. EP2
      mRNA and protein are expressed in endometrium and myometrium during the estrous
      cycle, whereas EP4 is undetectable. The Western analysis indicates that EP2 is
      maximally expressed in both endometrium and myometrium between d 10 and 18 of the
      estrous cycle. Immunohistochemical localization reveals that EP2 protein is
      expressed in all cell types of endometrium and myometrium. On d 18, pregnancy up
      regulates EP2 protein, primarily in endometrial stroma and myometrial smooth
      muscle cells. In conclusion, EP2 is the major cAMP-generating PGE(2) receptor
      expressed and regulated in the bovine uterus during the estrous cycle and early
      pregnancy.

PMID- 12810565
TI  - Functional role of inducible nitric oxide synthase in the induction of male germ
      cell apoptosis, regulation of sperm number, and determination of testes size:
      evidence from null mutant mice.
AB  - Inducible nitric oxide synthase (iNOS) through its product, nitric oxide (NO),
      may contribute to the induction of germ cell apoptosis. Using adult iNOS
      deficient mice, we characterized the reproductive hormonal profile and the
      testicular phenotype. Although there was no difference in body weight, mean
      testis weights in mutant mice were 30.77% higher, and testicular sperm count was
      65.51% higher than control animals. No significant differences were apparent in
      plasma LH, FSH, and testosterone levels between these mice. Compared with wild
      type mice, histomorphometric analysis showed that the mutant mice had a 39.63%
      increase in the number of pachytene spermatocytes and 33.79% in round spermatids,
      with no apparent changes in the number of preleptotene spermatocytes and
      spermatogonia. The incidence of spontaneous germ cell apoptosis detected by
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling assay was lower at stages I-IV and XI-XII of iNOS-mutant mice compared
      with wild-type animals. The rate of germ cell proliferation estimated by
      quantitative assessment of the bromodeoxyuridine labeled preleptotene
      spermatocytes showed no significant change between wild-type and iNOS-deficient
      mice. When applying testicular warming (43 C for 15 min) to mice, the rate of
      germ cell apoptosis was elevated predominantly at early (I-IV) and late (XI-XII)
      stages, and less during stages V-VI, VII-VIII, and IX-X at 2 and 6 h after heat
      exposure in the wild-type mice. In contrast, the rate of apoptosis in mutant mice
      was markedly decreased at early and late stages 2 and 6 h after heat exposure.
      Pachytene spermatocytes and early round spermatids were most susceptible to heat
      induced apoptosis in both mutant and control animals. Our studies demonstrate
      that: 1) deficiency of iNOS results in failure to eliminate a small portion of
      pachytene spermatocytes and round spermatids by apoptosis, resulting in a
      remarkable increase in testis weight and sperm output; 2) deficiency of iNOS
      confers partial resistance to heat-induced germ cell apoptosis. These experiments
      suggest that iNOS plays a physiological role in regulation of germ cell number
      and in determining testicular size.

PMID- 12810566
TI  - Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male
      reproductive tract.
AB  - The action of glucocorticoids in target tissues is dependent on the local
      expression of glucocorticoid receptors and two 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) enzymes, 11beta-HSD1 and 11beta-HSD2, which
      interconvert active and inactive glucocorticoids. This study examined expression
      of the 11beta-HSD enzymes in the male reproductive tract of the adult rat. 11beta
      HSD1 was immunolocalized to the apical region of principal epithelial cells of
      the caput epididymis, with the less numerous clear cells devoid of signal.
      Epididymal 11beta-HSD1 expression was confirmed by Western blot analysis, with
      immunoreactive species identified at 34 kDa (the expected size for 11beta-HSD1)
      and at approximately 48 kDa. 11beta-HSD bioactivity was readily detectable in the
      epididymis, with 11-oxoreductase activity clearly the favored reaction (as
      observed in liver), consistent with 11beta-HSD1 expression. The epithelium of the
      vas deferens, seminal vesicle, and penile urethra were also immunopositive for
      11beta-HSD1, as were smooth muscle cells of the vas deferens and penile blood
      vessels. 11beta-HSD2 was also immunolocalized to the epididymal epithelium, but
      its distribution was complementary to that of 11beta-HSD1 (i.e. clear cells
      showing intense 11beta-HSD2 staining but principal cells devoid of signal).
      11beta-HSD2 was also present in the corpora cavernosa of the penis but not in
      other tissues. In conclusion, the differential expression of 11beta-HSD1 and
      11beta-HSD2 throughout the male reproductive tract suggests that these enzymes
      locally modulate glucocorticoid and mineralocorticoid actions, particularly in
      the epididymis and penile vasculature.

PMID- 12810567
TI  - Interferon-stimulated gene-15 (Isg15) expression is up-regulated in the mouse
      uterus in response to the implanting conceptus.
AB  - An early response of the human and bovine endometrium to pregnancy is induction
      of an interferon (IFN)-stimulated gene (ISG) that encodes the ubiquitin-related
      protein, ISG15. Because the mode of implantation differs among species, we tested
      whether Isg15 mRNA was also expressed in the mouse uterus in response to the
      implanting conceptus. Isg15 mRNA was detected in the mouse uterus and increased
      after d 4.5 of pregnancy but did not change between d 3.5 and 9.5 of
      pseudopregnancy. Within the decidua, Isg15 mRNA was localized to the
      antimesometrial zone of the implantation sites. The level of Isg15 mRNA in
      artificially induced deciduomas was similar to the nonpregnant uterus and was
      approximately 10-fold lower than in the pregnant uterus. In vitro, murine
      decidual cells derived from artificially induced deciduomas could be induced to
      produce the Isg15 protein as well as Isg15-conjugated proteins when stimulated
      with type 1 IFN, though were less responsive to IFN-gamma. Isg15 is one of few
      gene products identified in murine implantation sites to require presence of the
      conceptus and not simply differentiation of the stroma. In vitro data support the
      inference that the pregnancy-specific inducer of uterine Isg15 is a type 1 IFN or
      a cytokine that signals through a similar pathway.

PMID- 12810568
TI  - Regulation of Sertoli cell tight junction dynamics in the rat testis via the
      nitric oxide synthase/soluble guanylate cyclase/3',5'-cyclic guanosine
      monophosphate/protein kinase G signaling pathway: an in vitro study.
AB  - Nitric oxide (NO) synthase (NOS) catalyzes the oxidation of L-arginine to NO. NO
      plays a crucial role in regulating various physiological functions, possibly
      including junction dynamics via its effects on cAMP and cGMP, which are known
      modulators of tight junction (TJ) dynamics. Although inducible NOS (iNOS) and
      endothelial NOS (eNOS) are found in the testis and have been implicated in the
      regulation of spermatogenesis, their role(s) in TJ dynamics, if any, is not
      known. When Sertoli cells were cultured at 0.5-1.2 x 10(6) cells/cm(2) on
      Matrigel-coated dishes or bicameral units, functional TJ barrier was formed when
      the barrier function was assessed by quantifying transepithelial electrical
      resistance across the cell epithelium. The assembly of the TJ barrier was shown
      to associate with a significant plummeting in the levels of iNOS and eNOS,
      seemingly suggesting that their presence by producing NO might perturb TJ
      assembly. To further confirm the role of NOS on the TJ barrier function in vitro,
      zinc (II) protoporphyrin-IX (ZnPP), an NOS inhibitor and a soluble guanylate
      cyclase inhibitor, was added to the Sertoli cell cultures during TJ assembly.
      Indeed, ZnPP was found to facilitate the assembly and maintenance of the Sertoli
      cell TJ barrier, possibly by inducing the production of TJ-associated proteins,
      such as occludin. Subsequent studies by immunoprecipitation and immunoblotting
      have shown that iNOS and eNOS are structurally linked to TJ-integral membrane
      proteins, such as occludin, and cytoskeletal proteins, such as actin, vimentin,
      and alpha-tubulin. When the cAMP and cGMP levels in these ZnPP-treated samples
      were quantified, a ZnPP-induced reduction of intracellular cGMP, but not cAMP,
      was indeed detected. Furthermore, 8-bromo-cGMP, a cell membrane-permeable analog
      of cGMP, could also perturb the TJ barrier dose dependently similar to the
      effects of 8-bromo-cAMP. KT-5823, a specific inhibitor of protein kinase G, was
      shown to facilitate the Sertoli cell TJ barrier assembly. Cytokines, such as TGF
      beta and TNF-alpha, known to perturb the Sertoli cell TJ barrier, were also shown
      to stimulate Sertoli cell iNOS and eNOS expression dose dependently in vitro.
      Collectively, these results illustrate NOS is an important physiological
      regulator of TJ dynamics in the testis, exerting its effects via the NO/soluble
      guanylate cyclase/cGMP/protein kinase G signaling pathway.

PMID- 12810569
TI  - Differentiation-dependent expression of 17beta-hydroxysteroid dehydrogenase, type
      10, in the rodent testis: effect of aging in Leydig cells.
AB  - Expression of the new 17beta-hydroxysteroid dehydrogenase (HSD), type 10 (17beta
      HSD-10), formerly known as endoplasmic reticulum-associated amyloid-binding
      protein, has been investigated in the testes of various mammals under normal and
      perturbed conditions. Results show that 17beta-HSD-10 is a major product of both
      fetal and adult-type Leydig cells. In the former, protein persists until late in
      postnatal development; and in the short-day hamster model, it does not disappear
      when Leydig cells involute. During puberty in the rat, immunohistochemical
      staining for 17beta-HSD-10 in adult-type Leydig cells first becomes evident on d
      20, increasing to maximal staining intensity by d 35. In the rat, but not in the
      mouse or any other species examined, there is also staining in late spermatids.
      Examination of testes from rats subjected to perinatal treatment with either a
      GnRH antagonist or low and high doses of diethylstilbestrol revealed that
      expression of 17beta-HSD-10 follows closely Leydig cell differentiation status,
      correlating with 3beta-HSD expression in a previous study. In aging (23 months)
      rat testes, Leydig cell (but not germ cell) immunostaining for 17beta-HSD-10 is
      markedly reduced. 17beta-HSD-10 seems to preferentially convert 3alpha
      androstanediol into dihydrotestosterone, and estradiol to estrone. Thus,
      perinatal expression of this enzyme in fetal Leydig cells may contribute to
      protecting these cells from estrogens and encourage androgen formation.

PMID- 12810570
TI  - Sp3/Sp1 in the parathyroid gland: identification of an Sp1 deoxyribonucleic acid
      element in the parathyroid hormone promoter.
AB  - A highly conserved region in the PTH promoter was identified using the basic
      local alignment search tool (BLAST) 2 Sequences comparison. Strong specific
      complexes were observed with a DNA probe that contained much of the computer
      derived conserved sequence in the EMSA using bovine parathyroid gland (bPTG)
      nuclear extracts. Ethylation interference footprinting indicated that the major
      complex made contacts to a sequence strikingly similar to an Sp1 binding site.
      Sp3 was evident in the major DNA-binding complexes, whereas the contribution by
      Sp1 was substantially weaker. Specific binding by additional unidentified bPTG
      nuclear factors was also evident. Immunocytochemical and Western blotting
      analyses established that Sp1 and Sp3 were positively localized in the nuclei of
      chief cells of the bPTG and of the expected molecular weights, with particularly
      robust expression of Sp3. Affinity DNA-binding experiments using the bovine PTH
      Sp1 element demonstrated specific recovery of intact Sp3 and Sp1 proteins,
      although a significant portion of both proteins failed to interact with the
      affinity-tagged DNA. Treatment of the bPTG nuclear extracts with phosphatase,
      however, significantly increased the DNA-binding capacity of the Sp1/Sp3
      complexes. Finally, transient transfection analysis indicated that the bovine Sp1
      like element acted as an enhancer of heterologous gene expression. The present
      study identified an Sp1 element in the promoter of the PTH gene that represents a
      complex DNA-binding site involving interactions primarily with Sp1/Sp3 proteins.
      The data, therefore, highlight the likely involvement of the Sp family in
      regulating PTH gene expression through interactions with an Sp1 DNA element in
      the hormone's promoter.

PMID- 12810571
TI  - Ini, a small nuclear protein that enhances the response of the connexin43 gene to
      estrogen.
AB  - This article describes the structural and functional characterization of Ini
      (AF495522), a novel highly conserved zinc-finger protein that had been identified
      by screening an estrogen-induced rat myometrial expression library. Ini localizes
      to the nucleus of HeLa cells and binds to the proximal connexin43 (cx43)
      promoter, as demonstrated by EMSA. In addition, transient transfection
      experiments performed with estrogen receptor alpha (ERalpha) cDNA show that
      overexpression of Ini enhances, in a dose-dependent fashion, the up-regulation of
      the cx43 gene by estrogen. On binding to the cx43 promoter, Ini stimulates the
      transcriptional activating function (AF)-1, but not the AF-2, of the ERalpha.
      This makes Ini one of the few known coactivators specific for AF-1. Because
      estrogen up-regulates Ini mRNA in the myometrium, it is likely that Ini's
      physiological role in this tissue is to modulate the response of the cx43 gene to
      estrogen. Transfection studies with an Ini antisense construct seem to indicate
      that Ini plays an additional role in the cellular response to estrogen affecting
      both AF-1 and AF-2 activities of the ERalpha. This broader effect may be
      associated with cell cycle progression that in yeast has been shown to require
      Ini.

PMID- 12810572
TI  - Response-specific and ligand dose-dependent modulation of estrogen receptor (ER)
      alpha activity by ERbeta in the uterus.
AB  - Estrogen is of great importance in the regulation of uterine function. The aim of
      this study was to examine the individual physiological roles of each of the two
      receptors for estradiol, estrogen receptor (ER) alpha and ERbeta, and their
      potential comodulatory effects on gene expression and uterine growth using
      recently developed ER subtype-selective agonist ligands. The use of ER subtype
      selective ligands provides an alternative, complementary approach to the use of
      receptor knockout mice. Administration of the ERalpha-selective ligand propyl
      pyrazole triol (PPT) to immature mice resulted in a significant increase in
      uterine weight, as well as bromodeoxyuridine incorporation and proliferating cell
      nuclear antigen expression in luminal epithelial cells. PPT also increased
      complement component 3, lactoferrin, and glucose-6-phosphate dehydrogenase
      (G6PDH), and decreased androgen receptor (AR) and progesterone receptor (PR) mRNA
      levels in uterine tissue, as did estradiol (E(2)). However, when compared with
      E(2), PPT was less effective in stimulating uterine weight, complement component
      3, and G6PDH expression but was as effective as E(2) in regulating lactoferrin,
      AR, and PR expression. In contrast to the action of the ERalpha agonist PPT, the
      ERbeta agonist diarylpropionitrile (DPN) did not increase uterine weight or
      luminal epithelial cell proliferation at a dose that reduced G6PDH and elicited a
      decrease in PR and AR mRNA and protein expression. Interestingly, DPN reduced the
      uterine weight stimulation by PPT, and enhanced the effect of PPT in decreasing
      uterine PR and AR mRNA. These findings with ER subtype-selective ligands indicate
      that ERalpha is the major regulator of estrogen function in the uterus, but that
      ERbeta does exert effects on some uterine markers of estrogen action. In
      addition, ERbeta can modulate ERalpha activity in a response-specific and dose
      dependent manner.

PMID- 12810573
TI  - Key apoptotic pathways for heat-induced programmed germ cell death in the testis.
AB  - Short-term exposure (43 C for 15 min) of the rat testis to mild heat results
      within 6 h in stage- and cell-specific activation of germ cell apoptosis.
      Initiation of apoptosis was preceded by a redistribution of Bax from a
      cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we
      show that the relocation of Bax is accompanied by cytosolic translocation of
      cytochrome c and is associated with activation of the initiator caspase 9 and the
      executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase.
      Furthermore, early in apoptosis, a significant amount of Bax also accumulates in
      endoplasmic reticulum, as assessed by Western blot analyses of fractionated
      testicular lysates. In additional studies using the FasL-defective gld mice, we
      have shown that heat-induced germ cell apoptosis is not blocked, thus providing
      evidence that the Fas signaling system may be dispensable for heat-induced germ
      cell apoptosis in the testis. Taken together, these results demonstrate that the
      mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the
      key apoptotic pathways for heat-induced germ cell death in the testis.

PMID- 12810574
TI  - Functional assessment of the thyrotropin receptor-beta subunit.
AB  - Posttranslational processing of the TSH receptor (TSHR) involves proteolysis of a
      single chain holoreceptor into TSHR-alpha (or A) and TSHR-beta (or B) subunits,
      which remain associated via disulfide bonds and which may then form oligomers. As
      both uncleaved and cleavage-derived forms of this receptor have been reported to
      bind TSH and transduce signals, reasons for this cleavage into alpha- and beta
      subunits have remained enigmatic. Recently we suggested that TSHR cleavage was
      related to receptor oligomerization and now we have asked if cleavage influenced
      the binding of G proteins to this receptor. Furthermore, as TSHR-alpha subunits
      are subject to shedding from the cell surface membrane, we have examined whether
      the remaining TSHR-beta subunits could mediate signaling themselves, either
      constitutively and /or ligand-induced. We found that only the cleaved form of the
      TSHR in transfected Chinese hamster ovary cells was able to bind Gsalpha protein,
      suggesting that cleavage of the native TSH receptor was associated with receptor
      activation. We also found that independently expressed TSHR-beta subunits on
      stable cell lines were unable to mediate either constitutive or TSH-induced
      signaling, as monitored by their inability to induce cAMP accumulation. These
      data suggested that receptor cleavage was intimately associated with receptor
      activation in the wild-type TSH receptor and that the residual TSHR-beta subunits
      left on the thyroid cell membrane, after TSHR cleavage and subsequent TSHR-alpha
      shedding, were essentially silent and did not participate in signal transduction.

PMID- 12810575
TI  - Nuclear translocation and retention of growth hormone.
AB  - We have previously demonstrated that GH is subject to rapid receptor-dependent
      nuclear translocation. Here, we examine the importance of ligand activation of
      the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization
      for hormone internalization and nuclear translocation by use of cells stably
      transfected with cDNA for the GHR. Staurosporine and herbimycin A treatment of
      cells did not affect the ability of GH to internalize but resulted in increased
      nuclear accumulation of hormone. Similarly, receptor mutations, which prevent the
      association and activation of JAK2, did not affect the ability of the hormone to
      internalize or translocate to the nucleus but resulted in increased nuclear
      accumulation of GH. These results were observed both by nuclear isolation and
      confocal laser scanning microscopy. Staurosporine treatment of cells in which
      human GH (hGH) was targeted to the cytoplasm (removal of secretion sequence) or
      to the nucleus (addition of the nuclear localization sequence of SV40 large T
      antigen) resulted in preferential accumulation of hGH in the nucleus. We further
      investigated the requirement of receptor dimerization for GH nuclear
      translocation using the non-receptor-dimerizing hGH antagonist, hGH-G120R,
      conjugated to fluorescein isothiocyanate. Confocal laser scanning microscopy
      demonstrated efficient internalization of both hGH and hGH-G120R but lack of
      nuclear translocation of hGH-G120R. Thus, we conclude that activation of JAK2
      kinase and the subsequent tyrosine phosphorylation is not required for nuclear
      translocation of GH but is pivotal for the removal of the hormone from the
      nucleus, and that GH translocates into the nucleus in a GHR dimerized-dependent
      fashion.

PMID- 12810576
TI  - Prostate development and carcinogenesis in prolactin receptor knockout mice.
AB  - Hyperprolactinemia results in prostatic hypertrophy and hyperplasia, but it is
      not known whether prolactin plays an essential role in these processes in the
      prostate. To address this question, we investigated prostate development, gene
      expression, and simian virus 40 (SV40)T-induced prostate carcinogenesis in
      prolactin receptor knockout mice. These animals showed a small increase in
      dorsolateral and ventral prostate weight but no change in the weight of the
      anterior prostate. The dorsal but not ventral or lateral lobes showed a 12% loss
      of epithelial cells; all other morphological parameters were normal. The area of
      SV40T-induced prostate intraepithelial neoplasia was reduced by 28% in the
      ventral lobe but not the dorsal lobe, and no tumors were seen in 20 prolactin
      receptor knockout animals, compared with 1 of 11 detected in wild-type and 4 of
      21 found in heterozygous animals. Oligonucleotide microarrays were used to
      identify essential transcriptional roles of prolactin and revealed a small set of
      genes with decreased expression involved in sperm/oocyte interaction and
      copulatory plug formation. Infertility or reduced fertility was apparent in these
      animals. These findings establish essential though subtle roles for prolactin in
      the regulation of prostate morphology, gene expression, SV40T-induced neoplasia,
      and reproductive function.

PMID- 12810577
TI  - Bisphenol a induces both transient and permanent histofunctional alterations of
      the hypothalamic-pituitary-gonadal axis in prenatally exposed male rats.
AB  - Exposure to bisphenol A (BPA) in utero has been shown to induce alterations in
      the prostate of 30-d-old Wistar rats. Herein, we examine both the time course of
      BPA action on the rat prostate and the effects of BPA on the male hypothalamic
      pituitary-gonadal axis. This was achieved by exposing rats to BPA in utero,
      followed by immunohistochemistry and morphometric analysis of prostatic tissue,
      evaluation of estrogen receptor-alpha (ERalpha) and ERbeta mRNA expression in
      both the preoptic area (POA) and medial basal hypothalamus, and determination of
      PRL, LH, and testosterone serum levels. On d 30 (peripubertal period), the
      prostatic periductal stroma of BPA-exposed rats demonstrated a significantly
      larger layer of fibroblasts than that of controls, whereas on d 120 (adulthood)
      no significant differences were observed. Moreover, BPA-exposed rats on d 15
      exhibited an increase in stromal cellular proliferation compared with controls.
      Decreased expression of both androgen receptor in prostatic stromal cells and
      prostatic acid phosphatase in epithelial cells was observed only on d 30 in BPA
      exposed males. BPA did not alter POA ERalpha mRNA expression, whereas a 4-fold
      increase in POA ERbeta mRNA expression was observed on both d 30 and 120. No
      alterations were observed in either ERalpha or ERbeta expression in the medial
      basal hypothalamus. BPA-exposed males exhibited increased PRL levels only on d
      30, whereas a transient increase in serum testosterone levels was observed on d
      15. These results support the hypothesis that prenatal exposure to environmental
      doses of BPA induces both transient and permanent age-dependent alterations in
      the male reproductive axis at different levels.

PMID- 12810578
TI  - Urocortin III is expressed in pancreatic beta-cells and stimulates insulin and
      glucagon secretion.
AB  - Urocortin (Ucn) III, or stresscopin, is a high affinity ligand for the type 2
      corticotropin-releasing factor (CRFR2) receptor recently identified in rodents
      and human. Ucn III was initially identified as a neuropeptide expressed in
      discrete areas in the brain. In the present study, we demonstrate that Ucn III is
      expressed in pancreatic beta-cells and in a mouse beta-cell line, MIN6. Ucn III
      secretion from the cells was measured using a highly specific RIA, and we found
      that high potassium, forskolin, or high glucose can stimulate Ucn III secretion
      from these cells. In vivo studies showed that rats receiving an iv Ucn III
      injection had a significant elevation of plasma glucagon followed by plasma
      glucose levels compared with rats receiving vehicle. Ucn III injections also
      result in an increase in plasma insulin levels. The observed effects of Ucn III
      were blocked by pretreatment with a CRFR2 antagonist, astressin(2)-B.
      Furthermore, Ucn III stimulated glucagon and insulin release from isolated rat
      islets, and astressin(2)-B abolished the effects of Ucn III, in keeping with a
      CRFR2-mediated mechanism. Taken together, the present studies suggest pancreatic
      Ucn III acting through CRFR2 is involved in the local regulation of glucagon and
      insulin secretion.

PMID- 12810579
TI  - Central orexin A has site-specific effects on luteinizing hormone release in
      female rats.
AB  - Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites
      of action of orexin A in the regulation of LH release have been investigated in
      vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB),
      with or without an injection of progesterone 48 h later. Orexin A was
      administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or
      vehicle; its effects on plasma LH levels were monitored in sequential blood
      samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area
      (rPOA) at the level of the organum vasculosum of the lamina terminalis had a
      stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A
      was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an
      inhibitory effect on the LH surge that occurs in ovariectomized rats primed with
      EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in
      ovariectomized rats untreated with ovarian steroids. Both the stimulatory and
      inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin
      1 receptor antagonist. Furthermore, when given alone into the rPOA, this
      antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin
      appears to have a dual effect on LH release, being stimulatory in the rPOA and
      inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated,
      at least in part, by the orexin 1 receptor. Double label immunohistochemistry
      revealed close appositions between orexin A immunoreactive varicosities and a
      small proportion of GnRH cell bodies in the rPOA. It is suggested that the
      stimulatory effect of orexin A on LH release may involve direct actions on GnRH
      neurons.

PMID- 12810581
TI  - Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine
      L cells.
AB  - Glucagon-like peptide 1 (GLP-1) released from distal intestinal endocrine L cells
      after food intake is a potent glucose-dependent stimulant of insulin secretion.
      Plasma levels of GLP-1 rise rapidly after nutrient ingestion through an indirect
      mechanism triggered from the proximal intestine and involving the vagus nerve.
      Our previous studies showed the involvement of M1 muscarinic receptors expressed
      by the L cells in the regulation of postprandial GLP-1 secretion in rats. The
      goal of this study was to explore the involvement of muscarinic receptors in the
      regulation of GLP-1 secretion by human L cells using a newly described human L
      cell line (NCI-H716). Phorbol 12-myristate 13-acetate (positive control)
      stimulated GLP-1 secretion to 252 +/- 38% of the control (P < 0.001).
      Bethanechol, a nonselective muscarinic agonist, significantly stimulated GLP-1
      secretion to 187 +/- 20% of the control (P < 0.01, n = 8). Pirenzepine (M1
      antagonist; 10-1000 microM) and gallamine (M2 antagonist; 10-1000 microM)
      completely inhibited bethanechol-induced GLP-1 secretion, whereas 4
      diphenylacetoxy-N-methylpiperidine (M3 antagonist) had no effect on bethanechol
      stimulated GLP-1 secretion. McN-A-343 (M1 muscarinic agonist) dose dependently
      stimulated GLP-1 secretion (to 252 +/- 50% of control at 1000 microM; P < 0.01),
      whereas oxotremorine (M3 agonist) had no effect. M1, M2, and M3 muscarinic
      receptors were shown to be expressed in NCI-H716 cells by Western blot,
      immunohystochemistry, and RT-PCR. Expression of the M1, M2, and M3 muscarinic
      receptor subtypes was also confirmed in paraffin-embedded human small intestine
      sections by double immunofluorescent staining. These results demonstrate the role
      of M1 and M2 muscarinic receptors expressed by human L cells in the control of
      GLP-1 secretion.

PMID- 12810580
TI  - Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus
      syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian
      development.
AB  - Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a human disorder
      caused by mutations in the forkhead transcription factor gene FOXL2 and is
      characterized by facial dysmorphology combined in some cases with ovarian
      failure. To better understand the role of FOXL2 in the etiology of ovarian
      failure in BPES, we examined its expression in embryonic ovaries of mice,
      chickens, and red-eared slider turtles, representatives of three phylogenetically
      distant vertebrate groups that have different mechanisms of sex determination.
      Expression of Foxl2 was detected in early ovaries of all three species around the
      time of sex determination and was associated with both somatic and germ cell
      populations in mice. Expression was sexually dimorphic in all cases. Sequence
      analysis of turtle and chicken FoxL2 orthologues indicated an unusually high
      degree of structural conservation during evolution. FoxL2 was found to be
      autosomal in chickens, and therefore unlikely to represent the dominant ovarian
      determining gene that has been postulated to exist as a possible explanation for
      female heterogamety in birds. Our observations suggest that BPES may result from
      early abnormalities in regulating the development of the fetal ovary, rather than
      premature degeneration of the postnatal or adult ovary. Further, our results
      suggest that FOXL2 is a highly conserved early regulator of vertebrate ovarian
      development.

PMID- 12810582
TI  - Estrogen regulates adrenal angiotensin AT1 receptors by modulating AT1 receptor
      translation.
AB  - Hypertension and associated cardiovascular disease increase after menopause.
      Angiotensin AT(1) receptor (AT(1)R) antagonists are effective treatments, in
      part, by inhibiting angiotensin II (Ang II)-induced aldosterone release from the
      adrenal zona glomerulosa (ZG). Estrogen decreases the number of AT(1)Rs in the
      adrenal gland and attenuates acute Ang II-induced aldosterone release. Here, we
      examined the effects of 17beta-estradiol (E(2)) on AT(1)R gene regulation in the
      rat adrenal cortex (AC). Female rats were ovariectomized and injected with
      vehicle or E(2). Immunohistochemistry revealed the presence of both estrogen
      receptor (ER)alpha and ERbeta in the ZG, and E(2) treatment increased the
      intensity of their nuclear staining. Under conditions in which AT(1)R maximal
      binding capacity was decreased by 46%, chronic miniosmotic pump Ang II-induced
      aldosterone secretion was reduced by 43%. E(2) treatment had no effect on AT(1a)R
      and AT(1b)R mRNA levels in the AC, whereas the AT(1)R mRNA polysome distribution
      in sucrose gradients was shifted to lighter fractions, indicating that E(2)
      treatment reduces AT(1)R translation. RNA binding proteins (RBPs) in AC extracts
      formed complexes with the 5' leader sequence (5'LS), coding region, and the 3'
      untranslated region (3'UTR); however, only the activity of 5'LS RBPs was
      regulated by E(2) treatment. These data suggest that E(2), acting through its
      receptors in the ZG, reduces AT(1)R density and Ang II-induced aldosterone
      release, primarily by inhibiting AT(1)R translation, possibly by blocking
      ribosomal scanning caused by increased steric hindrance from 5'LS RBPs.
      Dysregulation of this posttranscriptional mechanism may contribute to the
      increased incidence of cardiovascular disease associated with menopause.

PMID- 12810583
TI  - A novel retro-inverso gonadotropin-releasing hormone (GnRH) immunogen elicits
      antibodies that neutralize the activity of native GnRH.
AB  - GnRH vaccines have been successfully used for the inhibition of gonadotropin
      secretion and gonadal function. As an alternative to native GnRH, retro-inverso
      (RI) GnRH might be an improved immunogen. The RI peptides are composed of D-amino
      acids assembled in the reverse order (C to N terminus) in relation to the parent
      L peptide. These peptides are immunogenic and can produce high titers of
      antibodies that bind the parent peptide with high affinity and specificity. We
      show that RI-GnRH peptides conjugated to ovalbumin as well as unconjugated RI
      GnRH elicit high titers of anti-GnRH antibodies in rabbits and mice. Antibodies
      were affinity purified and shown by ELISA to be selective for mammalian GnRH
      compared with GnRH II and [Gln(8)]GnRH. The binding kinetics of antibody-peptide
      interactions was determined using biosensor technology (BIACORE). The purified
      anti-GnRH antibodies inhibited GnRH-stimulated signal transduction in COS-1 cells
      expressing the human GnRH receptor. Immunization of mice with unconjugated and
      conjugated RI-GnRH peptide, in the absence of complete Freund's adjuvant,
      produced antisera that cross-reacted with mammalian GnRH. As RI peptides are
      resistant to cleavage by proteolytic enzymes, they are potentially orally active.
      The ability of RI-GnRH peptides to produce antibodies to GnRH without conjugation
      and without Freund's complete adjuvant constitutes a novel vaccine with improved
      properties of potential application in animal management and sex hormone
      dependent cancers.

PMID- 12810584
TI  - Rb and p107 are required for normal cerebellar development and granule cell
      survival but not for Purkinje cell persistence.
AB  - The involvement of the retinoblastoma gene product (Rb) and its family members
      (p107 and p130) in cell cycle exit and terminal differentiation of neural
      precursor cells has been demonstrated in vitro. To investigate the roles of Rb
      and p107 in growth, differentiation and apoptosis in the developing and mature
      cerebellum, we selectively inactivated either Rb alone or in combination with
      p107 in cerebellar precursor cells or in Purkinje cells. In our mouse models, we
      show that (1) Rb is required for differentiation, cell cycle exit and survival of
      granule cell precursors; (2) p107 can not fully compensate for the loss of Rb
      function in granule cells; (3) Rb and p107 are not required for differentiation
      and survival of Purkinje cells during embryonic and early postnatal development;
      (4) Rb function in Purkinje cells is cell autonomous; and (5) loss of Rb
      deficient CNS precursor cells is mediated by p53-independent apoptosis.

PMID- 12810585
TI  - The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3
      pharynx motoneuron function.
AB  - Several homeobox genes, for example those of the ems class, play important roles
      in animal head development. We report on the expression pattern and function of
      ceh-2, the Caenorhabditis elegans ems/Emx ortholog. CEH-2 protein is restricted
      to the nuclei of one type of small muscle cell, one type of epithelial cell, and
      three types of neurons in the anterior pharynx in the head. We have generated a
      deletion allele of ceh-2 that removes the homeobox. Animals homozygous for this
      deletion are viable and fertile, but grow slightly slower and lay fewer eggs than
      wild type. We assayed the function of two types of pharynx neurons that express
      ceh-2, the pairs M3 and NSM. M3 activity is substantially reduced in
      electropharyngeograms of ceh-2 deletion mutants; this defect can account for the
      observed retardation in larval development, as M3 activity is known to be
      necessary for effective feeding. NSM function and metabolism are normal based on
      the assays used. All cells that express ceh-2 in wild type are present in the ceh
      2 mutant and have normal morphologies. Therefore, unlike other ems/Emx genes, ceh
      2 seems to be important for a late differentiation step and not for neuron
      specification or regional patterning. Because the CEH-2 homeodomain is well
      conserved, we tested whether ceh-2 can rescue ems(-) brain defects in Drosophila,
      despite the apparent differences in biological roles. We found that the C.
      elegans ems ortholog is able to substitute for fly ems in brain development,
      indicating that sequence conservation rather than conservation of biological
      function is important.

PMID- 12810586
TI  - Fgf3 and Fgf10 are required for mouse otic placode induction.
AB  - The inner ear, which contains the sensory organs specialised for audition and
      balance, develops from an ectodermal placode adjacent to the developing
      hindbrain. Tissue grafting and recombination experiments suggest that placodal
      development is directed by signals arising from the underlying mesoderm and
      adjacent neurectoderm. In mice, Fgf3 is expressed in the neurectoderm prior to
      and concomitant with placode induction and otic vesicle formation, but its
      absence affects only the later stages of otic vesicle morphogenesis. We show here
      that mouse Fgf10 is expressed in the mesenchyme underlying the prospective otic
      placode. Embryos lacking both Fgf3 and Fgf10 fail to form otic vesicles and have
      aberrant patterns of otic marker gene expression, suggesting that FGF signals are
      required for otic placode induction and that these signals emanate from both the
      hindbrain and mesenchyme. These signals are likely to act directly on the
      ectoderm, as double mutant embryos showed normal patterns of gene expression in
      the hindbrain. Cell proliferation and survival were not markedly affected in
      double mutant embryos, suggesting that the major role of FGF signals in otic
      induction is to establish normal patterns of gene expression in the prospective
      placode. Finally, examination of embryos carrying three out of the four mutant
      Fgf alleles revealed intermediate phenotypes, suggesting a quantitative
      requirement for FGF signalling in otic vesicle formation.

PMID- 12810587
TI  - Regulation of myosin expression during myotome formation.
AB  - The first skeletal muscle fibers to form in vertebrate embryos appear in the
      somitic myotome. PCR analysis and in situ hybridization with isoform-specific
      probes reveal differences in the temporal appearance and spatial distribution of
      fast and slow myosin heavy chain mRNA transcripts within myotomal fibers.
      Embryonic fast myosin heavy chain was the first isoform expressed, followed
      rapidly by slow myosin heavy chains 1 and 3, with slow myosin heavy chain 2
      appearing several hours later. Neonatal fast myosin heavy chain is not expressed
      in myotomal fibers. Although transcripts of embryonic fast myosin heavy chain
      were always distributed throughout the length of myotomal fibers, the mRNA for
      each slow myosin heavy chain isoform was initially restricted to the centrally
      located myotomal fiber nuclei. As development proceeded, slow myosin heavy chain
      transcripts spread throughout the length of myotomal fibers in order of their
      appearance. Explants of segments from embryos containing neural tube, notochord
      and somites 7-10, when incubated overnight, become innervated by motor neurons
      from the neural tube and express all four myosin heavy chain genes. Removal of
      the neural tube and/or notochord from explants prior to incubation or addition of
      d-tubocurare to intact explants prevented expression of slow myosin chain 2 but
      expression of genes encoding the other myosin heavy chain isoforms was
      unaffected. Thus, expression of slow myosin heavy chain 2 is dependent on
      functional innervation, whereas expression of embryonic fast and slow myosin
      heavy chain 1 and 3 are innervation independent. Implantation of sonic-hedgehog
      soaked beads in vivo increased the accumulation of both fast and slow myosin
      heavy chain transcripts, as well as overall myotome size and individual fiber
      size, but had no effect on myotomal fiber phenotype. Transcripts encoding
      embryonic fast myosin heavy chain first appear ventrolaterally in the myotome,
      whereas slow myosin heavy chain transcripts first appear in fibers positioned
      midway between the ventrolateral and dorsomedial lips of the myotome. Therefore,
      models of epaxial myotome formation must account for the positioning of the
      oldest fibers in the more ventral-lateral region of the myotome and the youngest
      fibers in the dorsomedial region.

PMID- 12810588
TI  - Mesenchymal patterning by Hoxa2 requires blocking Fgf-dependent activation of
      Ptx1.
AB  - Hox genes are known key regulators of embryonic segmental identity, but little is
      known about the mechanisms of their action. To address this issue, we have
      analyzed how Hoxa2 specifies segmental identity in the second branchial arch.
      Using a subtraction approach, we found that Ptx1 was upregulated in the second
      arch mesenchyme of Hoxa2 mutants. This upregulation has functional significance
      because, in Hoxa2(-/-);Ptx1(-/-) embryos, the Hoxa2(-/-) phenotype is partially
      reversed. Hoxa2 interferes with the Ptx1 activating process, which is dependent
      on Fgf signals from the epithelium. Consistently, Lhx6, another target of Fgf8
      signaling, is also upregulated in the Hoxa2(-/-) second arch mesenchyme. Our
      findings have important implications for the understanding of developmental
      processes in the branchial area and suggest a novel mechanism for mesenchymal
      patterning by Hox genes that acts to define the competence of mesenchymal cells
      to respond to skeletogenic signals.

PMID- 12810590
TI  - Monitoring neural progenitor fate through multiple rounds of division in an
      intact vertebrate brain.
AB  - The behaviour of neural progenitors in the intact vertebrate brain and spinal
      cord is poorly understood, chiefly because of the inaccessibility and poor
      optical qualities inherent in many model systems. To overcome these problems we
      have studied the optically superior brain of the zebrafish embryo and have
      monitored the in vivo behaviour of fluorescently labelled neural progenitors and
      their daughter cells throughout a substantial period of hindbrain development. We
      find the majority (84%) of hindbrain neurons are born from progenitor divisions
      that generate two neurons and 68% of reconstructed lineage trees contained no
      asymmetric stem cell-like divisions. No progenitors divided in the manner
      expected of a classic stem cell; i.e. one that repeatedly self-renews and
      generates a differentiated cell type by asymmetric division. We also analysed the
      orientation of progenitor divisions relative to the plane of the ventricular zone
      (VZ) and find that this does not correlate with the fate of the daughter cells.
      Our results suggest that in this vertebrate system the molecular determinants
      that control whether a cell will become a neuron are usually not linked to a
      mechanism that generates asymmetric divisions.

PMID- 12810589
TI  - Analysis of a key regulatory region upstream of the Myf5 gene reveals multiple
      phases of myogenesis, orchestrated at each site by a combination of elements
      dispersed throughout the locus.
AB  - Myf5 is the first myogenic regulatory factor to be expressed in the mouse embryo
      and it determines the entry of cells into the skeletal muscle programme. A region
      situated between -58 kb and -48 kb from the gene directs Myf5 transcription at
      sites where muscles will form. We now show that this region consists of a number
      of distinct regulatory elements that specifically target sites of myogenesis in
      the somite, limbs and hypoglossal cord, and also sites of Myf5 transcription in
      the central nervous system. Deletion of these sequences in the context of the
      locus shows that elements within the region are essential, and also reveals the
      combinatorial complexity of the transcriptional regulation of Myf5. Both within
      the -58 kb to -48 kb region and elsewhere in the locus, multiple sequences are
      present that direct transcription in subdomains of a single site during
      development, thus revealing distinct phases of myogenesis when subpopulations of
      progenitor cells enter the programme of skeletal muscle differentiation.

PMID- 12810591
TI  - Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals
      involved.
AB  - We have previously shown that human myoblasts do not fuse when their voltage
      fails to reach the domain of a window T-type Ca(2+) current. We demonstrate, by
      changing the voltage in the window domain, that the Ca(2+) signal initiating
      fusion is not of the all-or-none type, but can be graded and is interpreted as
      such by the differentiation program. This was carried out by exploiting the
      properties of human ether-a-go-go related gene K(+) channels that we found to be
      expressed in human myoblasts. Methanesulfonanilide class III antiarrhythmic
      agents or antisense-RNA vectors were used to suppress completely ether-a-go-go
      related gene current. Both procedures induced a reproducible depolarization from 
      74 to -64 mV, precisely in the window domain where the T-type Ca(2+) current
      increases with voltage. This 10 mV depolarization raised the cytoplasmic free
      Ca(2+) concentration, and triggered a tenfold acceleration of myoblast fusion.
      Our results suggest that any mechanism able to modulate intracellular Ca(2+)
      concentration could affect the rate of myoblast fusion.

PMID- 12810592
TI  - Formation of the adult pigment pattern in zebrafish requires leopard and obelix
      dependent cell interactions.
AB  - Colour patterns are a prominent feature of many animals and are of high
      evolutionary relevance. In zebrafish, the adult pigment pattern comprises
      alternating stripes of two pigment cell types, melanophores and xanthophores. How
      the stripes are defined and a straight boundary is formed remains elusive. We
      find that mutants lacking one pigment cell type lack a striped pattern. Instead,
      cells of one type form characteristic patterns by homotypic interactions. Using
      mosaic analysis, we show that juxtaposition of melanophores and xanthophores
      suffices to restore stripe formation locally. Based on this, we have analysed the
      pigment pattern of two adult specific mutants: leopard and obelix. We demonstrate
      that obelix is required in melanophores to promote their aggregation and controls
      boundary integrity. By contrast, leopard regulates homotypic interaction within
      both melanophores and xanthophores, and interaction between the two, thus
      controlling boundary shape. These findings support a view in which cell-cell
      interactions among pigment cells are the major driving force for adult pigment
      pattern formation.

PMID- 12810593
TI  - A dual, non-redundant, role for LIF as a regulator of development and STAT3
      mediated cell death in mammary gland.
AB  - STAT3 is the key mediator of apoptosis in mammary gland. We demonstrate here that
      LIF is the physiological activator of STAT3, because in involuting mammary glands
      of Lif(-/-) mice, pSTAT3 is absent and the STAT3 target, C/EBPdelta, is not
      upregulated. Similar to Stat3 knockouts, Lif(-/-) mammary glands exhibit delayed
      involution, reduced apoptosis and elevated levels of p53. Significantly, Lif(-/-)
      glands display precocious development during pregnancy, when pSTAT3 is not
      normally detected. We show that pERK1/2 is significantly reduced in Lif(-/-)
      glands at this time, suggesting that at this stage LIF mediates its effects
      through pERK1/2. Inhibition of LIF-mediated ERK1/2 phosphorylation potentiates
      the proapoptotic effects of STAT3. LIF therefore signals alternately through
      ERK1/2, then STAT3, to regulate mammary growth and apoptosis.

PMID- 12810594
TI  - PVF1, a PDGF/VEGF homolog, is sufficient to guide border cells and interacts
      genetically with Taiman.
AB  - The border cells of the Drosophila ovary undergo a well-defined and
      developmentally regulated cell migration. Two signals have previously been shown
      to control where and when the cells migrate. The steroid hormone ecdysone, acting
      through its receptor and a coactivator known as Taiman, contributes to regulating
      the timing of border cell migration. PVF1, a growth factor related to platelet
      derived growth factor and vascular-endothelial growth factor, contributes to
      guiding the border cells to the oocyte. To probe the mechanisms controlling
      border cell migration further, we performed a screen for genes that exhibit
      dominant genetic interactions with taiman. We identified 14 genomic regions that
      interact with taiman. Within one region, we identified Pvf1 as the gene
      responsible for the interaction. Signaling by PVF1 has been proposed to guide the
      border cells to their proper target, but ectopic PVF1 has not been tested for its
      ability to redirect the border cells. We tested the ability of PVF1, as well as
      other factors such as Gurken, to guide the border cells to new targets. Our
      results demonstrate that ectopic expression of PVF1 is sufficient to redirect
      border cells in some egg chambers but that the other factors tested are not.
      These data suggest that the guidance of border cell migration is robust and that
      there are likely to be additional factors that contribute to long-range guidance
      of these cells. In addition, we find that taiman and Pvf1 regulate the dynamic
      localization of E-cadherin in the border cells, possibly accounting for the
      interaction between these two pathways.

PMID- 12810595
TI  - The Drosophila dual-specificity ERK phosphatase DMKP3 cooperates with the ERK
      tyrosine phosphatase PTP-ER.
AB  - ERK MAP kinase plays a key role in relaying extracellular signals to
      transcriptional regulation. As different activity levels or the different
      duration of ERK activity can elicit distinct responses in one and the same cell,
      ERK has to be under strict positive and negative control. Although numerous genes
      acting positively in the ERK signaling pathway have been recovered in genetic
      screens, mutations in genes encoding negative ERK regulators appear
      underrepresented. We therefore sought to genetically characterize the dual
      specificity phosphatase DMKP3. First, we established a novel assay to elucidate
      the substrate preferences of eukaryotic phosphatases in vivo and thereby
      confirmed the specificity of DMKP3 as an ERK phosphatase. The Dmkp3
      overexpression phenotype characterized in this assay permitted us to isolate
      Dmkp3 null mutations. By genetic analysis we show that DMKP3 and the tyrosine
      phosphatase PTP-ER perform partially redundant functions on the same substrate,
      ERK. DMKP3 functions autonomously in a subset of photoreceptor progenitor cells
      in eye imaginal discs. In addition, DMKP3 function appears to be required in
      surrounding non-neuronal cells for ommatidial patterning and photoreceptor
      differentiation.

PMID- 12810596
TI  - Epiblast and primitive-streak origins of the endoderm in the gastrulating chick
      embryo.
AB  - Gastrulation is characterized by the extensive movements of cells. Fate mapping
      is used to follow such cell movements as they occur over time, and prospective
      fate maps have been constructed for several stages of the model organisms used in
      modern studies in developmental biology. In chick embryos, detailed fate maps
      have been constructed for both prospective mesodermal and ectodermal cells.
      However, the origin and displacement of the prospective endodermal cells during
      crucial periods in gastrulation remain unclear. This study had three aims. First,
      we determined the primitive-streak origin of the endoderm using supravital
      fluorescent markers, and followed the movement of the prospective endodermal
      cells as they dispersed to generate the definitive endodermal layer. We show that
      between stages 3a/b and 4, the intraembryonic definitive endoderm receives
      contributions mainly from the rostral half of the primitive streak, and that
      endodermal movements parallel those of ingressing adjacent mesodermal
      subdivisions. Second, the question of the epiblast origin of the endodermal layer
      was addressed by precisely labeling epiblast cells in a region known to give rise
      to prospective somitic cells, and following their movement as they underwent
      ingression through the primitive streak. We show that the epiblast clearly
      contributes prospective endodermal cells to the primitive streak, and
      subsequently to definitive endoderm of the area pellucida. Finally, the
      relationship between the hypoblast and the definitive endoderm was defined by
      following labeled rostral primitive-streak cells over a short period of time as
      they contributed to the definitive endoderm, and combining this with in situ
      hybridization with a riboprobe for Crescent, a marker of the hypoblast. We show
      that as the definitive endodermal layer is laid down, there is cell-cell
      intercalation at its interface with the displaced hypoblast cells. These data
      were used to construct detailed prospective fate maps of the endoderm in the
      chick embryo, delineating the origins and migrations of endodermal cells in
      various rostrocaudal levels of the primitive streak during key periods in early
      development.

PMID- 12810597
TI  - Wnt signalling regulates myogenic differentiation in the developing avian wing.
AB  - The limb musculature arises by delamination of premyogenic cells from the lateral
      dermomyotome. Initially the cells express Pax3 but, upon entering the limb bud,
      they switch on the expression of MyoD and Myf5 and undergo terminal
      differentiation into slow or fast fibres, which have distinct contractile
      properties that determine how a muscle will function. In the chick, the
      premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the
      cells differentiate, suggesting that Wnts might regulate myogenic
      differentiation. Here, we have investigated the role of Wnt signalling during
      myogenic differentiation in the developing chick wing bud by gain- and loss-of
      function studies in vitro and in vivo. We show that Wnt signalling changes the
      number of fast and/or slow fibres. For example, in vivo, Wnt11 decreases and
      increases the number of slow and fast fibres, respectively, whereas
      overexpression of Wnt5a or a dominant-negative Wnt11 protein have the opposite
      effect. The latter shows that endogenous Wnt11 signalling determines the number
      of fast and slow myocytes. The distinct effects of Wnt5a and Wnt11 are consistent
      with their different expression patterns, which correlate with the ultimate
      distribution of slow and fast fibres in the wing. Overexpression of activated
      calmodulin kinase II mimics the effect of Wnt5a, suggesting that it uses this
      pathway. Finally, we show that overexpression of the Wnt antagonist Sfrp2 and
      DeltaLef1 reduces the number of myocytes. In Sfrp2-infected limbs, the number of
      Pax3 expressing cells was increased, suggesting that Sfrp2 blocks myogenic
      differentiation. Therefore, Wnt signalling modulates both the number of
      terminally differentiated myogenic cells and the intricate slow/fast patterning
      of the limb musculature.

PMID- 12810598
TI  - The zebrafish fgf24 mutant identifies an additional level of Fgf signaling
      involved in vertebrate forelimb initiation.
AB  - The development of vertebrate limb buds is triggered in the lateral plate
      mesoderm by a cascade of genes, including members of the Fgf and Wnt families, as
      well as the transcription factor tbx5. Fgf8, which is expressed in the
      intermediate mesoderm, is thought to initiate forelimb formation by activating
      wnt2b, which then induces the expression of tbx5 in the adjacent lateral plate
      mesoderm. Tbx5, in turn, is required for the activation of fgf10, which relays
      the limb inducing signal to the overlying ectoderm. We show that the zebrafish
      fgf24 gene, which belongs to the Fgf8/17/18 subfamily of Fgf ligands, acts
      downstream of tbx5 to activate fgf10 expression in the lateral plate mesoderm. We
      also show that fgf24 activity is necessary for the migration of tbx5-expressing
      cells to the fin bud, and for the activation of shh, but not hand2, expression in
      the posterior fin bud.

PMID- 12810599
TI  - Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons.
AB  - The TrkA/NGF receptor is essential for the survival and differentiation of
      sensory neurons. The molecular mechanisms regulating tissue and stage-specific
      expression of TrkA are largely unknown. The Brn3a POU-domain transcription factor
      has been implicated in the development of the PNS and proposed as a transcription
      regulator for TrkA. The molecular mechanisms underlying the regulation of TrkA by
      Brn3a is unclear. In this study, we provide genetic, transgenic and biochemical
      evidence that Brn3a binds to novel, specific sites in the 457 bp enhancer that
      regulates TrkA expression in embryonic sensory neurons. We employ Bax-knockout
      mice, in which sensory neurons no longer require neurotrophins for survival, to
      uncouple TrkA-dependent cell death from downregulation of TrkA expression. In
      addition, when mutagenized, the novel Brn3a-binding sites identified fail to
      drive appropriate reporter transgene expression in sensory neurons. Thus, TrkA, a
      gene that is crucial for the differentiation and survival of sensory nociceptive
      neurons, requires Brn3a to maintain normal transcriptional activity.

PMID- 12810600
TI  - Crucial role of TrkB ligands in the survival and phenotypic differentiation of
      developing locus coeruleus noradrenergic neurons.
AB  - The role of glial cell-line derived neurotrophic factor (GDNF) and neurotrophins
      in the development of locus coeruleus noradrenergic neurons was evaluated. We
      found that two neurotrophic factors previously reported to prevent the
      degeneration of lesioned adult central noradrenergic neurons, GDNF and
      neurotrophin 3 (NT3), do not play significant roles in the prenatal development
      of locus coeruleus noradrenergic neurons, as demonstrated by: (1) the lack of
      alterations in double Gdnf/Nt3 null mutant mice; and (2) the lack of survival
      promoting effects of GDNF and/or NT3 in rat E13.5 primary cultures. In contrast,
      null mutant mice for TrkB, the tyrosine kinase receptor for brain-derived
      neurotrophic factor and neurotrophin 4, displayed a clear loss of locus coeruleus
      noradrenergic neurons. In accordance with this, treatment of rat E13.5 primary
      cultures with TrkB ligands prevented the early loss of noradrenergic neurons and
      maintained their survival for up to 6 days in vitro. Moreover, an additional 5-10
      fold increase in the number of tyrosine hydroxylase positive noradrenergic
      neurons was detected after 12 hours in culture. This second effect of TrkB
      ligands involved neither proliferation nor survival, because the number of BrdU-
      or TUNEL-positive noradrenergic neurons did not change and the effect was
      elicited by delayed administration of either factor. Because TrkB ligands
      increased the number of tyrosine hydroxylase-positive cells expressing Phox2a, a
      paired homeodomain protein required for the development of locus coeruleus
      noradrenergic neurons, but did not affect the number of Phox2a-positive tyrosine
      hydroxylase-negative cells, our results suggest that the second effect of TrkB
      ligands may involve promoting or inducing a noradrenergic phenotype. In summary,
      our findings suggest that, unlike NT3 and GDNF, TrkB ligands are required and
      sufficient to promote the development of central noradrenergic neurons.

PMID- 12810601
TI  - Establishment of POP-1 asymmetry in early C. elegans embryos.
AB  - In Caenhorabtidis elegans embryos, the nuclei of sister cells that are born from
      anterior/posterior divisions show an invariant high/low asymmetry, respectively,
      in their level of the transcription factor POP-1. Previous studies have shown
      that POP-1 asymmetry between the daughters of an embryonic cell called EMS
      results in part from a Wnt-like signal provided by a neighboring cell, called
      P(2). We identify here additional signaling cells that play a role in POP-1
      asymmetry for other early embryonic cells. Some of these cells have signaling
      properties similar to P(2), whereas other cells use apparently distinct signaling
      pathways. Although cell signaling plays a critical role in POP-1 asymmetry during
      the first few cell divisions, later embryonic cells have an ability to generate
      POP-1 asymmetry that appears to be independent of prior Wnt signaling.

PMID- 12810602
TI  - Macrophage-mediated corpse engulfment is required for normal Drosophila CNS
      morphogenesis.
AB  - Cell death plays an essential role in development, and the removal of cell
      corpses presents an important challenge for the developing organism. Macrophages
      are largely responsible for the clearance of cell corpses in Drosophila
      melanogaster and mammalian systems. We have examined the developmental
      requirement for macrophages in Drosophila and find that macrophage function is
      essential for central nervous system (CNS) morphogenesis. We generate and analyze
      mutations in the Pvr locus, which encodes a receptor tyrosine kinase of the
      PDGF/VEGF family that is required for hemocyte migration. We find that loss of
      Pvr function causes the mispositioning of glia within the CNS and the disruption
      of the CNS axon scaffold. We further find that inhibition of hemocyte development
      or of Croquemort, a receptor required for macrophage-mediated corpse engulfment,
      causes similar CNS defects. These data indicate that macrophage-mediated
      clearance of cell corpses is required for proper morphogenesis of the Drosophila
      CNS.

PMID- 12810603
TI  - The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge
      syndrome.
AB  - The chordin/Bmp system provides one of the best examples of extracellular
      signaling regulation in animal development. We present the phenotype produced by
      the targeted inactivation of the chordin gene in mouse. Chordin homozygous mutant
      mice show, at low penetrance, early lethality and a ventralized gastrulation
      phenotype. The mutant embryos that survive die perinatally, displaying an
      extensive array of malformations that encompass most features of DiGeorge and
      Velo-Cardio-Facial syndromes in humans. Chordin secreted by the mesendoderm is
      required for the correct expression of Tbx1 and other transcription factors
      involved in the development of the pharyngeal region. The chordin mutation
      provides a mouse model for head and neck congenital malformations that frequently
      occur in humans and suggests that chordin/Bmp signaling may participate in their
      pathogenesis.

PMID- 12810604
TI  - Pin1 regulates the timing of mammalian primordial germ cell proliferation.
AB  - Primordial germ cells (PGCs) give rise to male and female germ cells to transmit
      the genome from generation to generation. Defects in PGC development often result
      in infertility. In the mouse embryo, PGCs undergo proliferation and expansion
      during and after their migration to the gonads from 8.5 to 13.5 days post coitum
      (dpc). We show that a peptidyl-prolyl isomerase, Pin1, is involved in the
      regulation of mammalian PGC proliferation. We discovered that both the male and
      female Pin1(-/-) mice had profound fertility defects. Investigation of the
      reproductive organs revealed significantly fewer germ cells in the adult Pin1(-/
      ) testes and ovaries than in wild type or heterozygotes, which resulted from
      Pin1(-/-) males and females being born with severely reduced number of gonocytes
      and oocytes. Further studies in 8.5 to 13.5 dpc Pin1(-/-) embryos showed that
      PGCs were allocated properly at the base of the allantois, but their cell
      expansion was progressively impaired, resulting in a markedly reduced number of
      PGCs at 13.5 dpc. Analyses using markers of cell cycle parameters and apoptosis
      revealed that Pin1(-/-) PGCs did not undergo cell cycle arrest or apoptosis.
      Instead, Pin1(-/-) PGCs had a lower BrdU labeling index compared with wild-type
      PGCs. We conclude that PGCs have a prolonged cell cycle in the absence of Pin1,
      which translates into fewer cell divisions and strikingly fewer Pin1(-/-) PGCs by
      the end of the proliferative phase. These results indicate that Pin1 regulates
      the timing of PGC proliferation during mouse embryonic development.

PMID- 12810606
TI  - Lack of insulin receptor substrate-2 causes progressive neointima formation in
      response to vessel injury.
AB  - BACKGROUND: Insulin resistance is associated with atherosclerosis, but its
      mechanism is unknown. It has been reported that insulin receptor substrate (IRS)
      1 deficient (IRS-1-/-) mice showed insulin resistance without type 2 diabetes,
      whereas the IRS-2 deficient (IRS-2-/-) mice showed insulin resistance with type 2
      diabetes. METHODS AND RESULTS: We investigated neointima formation in the IRS-1-/
      and IRS-2-/- mice at 8 and 20 weeks. The IRS-2-/- mice showed much greater
      neointima formation than the IRS-1-/- and wild-type mice at 8 weeks. At 20 weeks,
      the IRS-2-/- mice had greater neointima formation than the IRS-1-/- mice, which
      showed more enhanced neointima formation than the wild-type mice. The IRS-1-/-
      and IRS-2-/- mice had dyslipidemia, hypertension, and insulin resistance. The IRS
      2-/- mice had more metabolic abnormalities than the IRS-1-/- mice at 8 and 20
      weeks. IRS-2 expression was detected, but IRS-1 expression was not detected in
      the vessels. CONCLUSIONS: The neointima formation in the IRS-1-/- and IRS-2-/-
      mice appears to be related to abnormalities induced by the altered metabolic
      milieu in insulin-resistant states. Moreover, because neointima formation was
      much greater in the IRS-2-/- mice than in the IRS-1-/- mice at 8 and 20 weeks, it
      is suggested that a lack of IRS-2 renders the vasculature more susceptible to
      injury in the abnormal metabolic milieu, and IRS-2 may have a protective effect
      on neointima formation. We conclude that IRS-2 is protective and retards the
      development of neointima formation in insulin-resistant states.

PMID- 12810607
TI  - Noncultured, autologous, skeletal muscle cells can successfully engraft into
      ovine myocardium.
AB  - BACKGROUND: There is compelling evidence showing that cellular cardiomyoplasty
      can improve cardiac function. Considering the potential benefit of using
      noncultured muscle cells (little time, lower cost, reduced risk of
      contamination), we investigated the feasibility of grafting cells obtained
      directly after enzymatic dissociation of skeletal muscle biopsies into ovine
      myocardium. We hypothesized that those noncultured muscle cells would engraft
      massively. METHODS AND RESULTS: Autologous, intramyocardial skeletal muscle cell
      implantation was performed in 8 sheep. A skeletal muscle biopsy sample (
      approximately 10 g) was explanted from each animal. The sheep were left to
      recover for approximately 3 hours and reanesthetized when the cells were ready
      for implantation. A left fifth intercostal thoracotomy was performed, and 10
      epicardial injections of the muscle preparation (between 10 and 20 million cells)
      were carried out. All sheep were euthanized 3 weeks after myocardial
      implantation. Immunohistochemistry was performed with monoclonal antibodies to a
      fast skeletal isoform of myosin heavy chain. Skeletal myosin heavy-chain
      expression was detected in all slides at 3 weeks after implantation in 8 of 8
      animals, confirming engraftment of skeletal muscle cells. Massive areas of
      engraftment (from 2 to 9 mm in diameter) or discrete loci were noted within the
      myocardial wall. CONCLUSIONS: Our results indicate that noncultured skeletal
      muscle cells can successfully and massively engraft in ovine myocardium. Thus,
      avoiding the cell culture expansion phase is feasible and could become a
      promising option for cellular cardiomyoplasty.

PMID- 12810608
TI  - Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2
      diabetes.
AB  - BACKGROUND: It is well known that patients with type 2 diabetes have increased
      risk of cardiovascular disease, but it is not known whether they have underlying
      abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism.
      METHODS AND RESULTS: We studied 21 patients with type 2 diabetes with no evidence
      of coronary artery disease or impaired cardiac function, as determined by
      echocardiography, and 15 age-, sex-, and body mass index-matched control
      subjects. Cardiac high-energy phosphate metabolites were measured at rest using
      31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy
      phosphate metabolites, intracellular pH, and oxygenation were measured using 31P
      MRS and near infrared spectrophotometry, respectively, before, during, and after
      exercise. Although their cardiac morphology, mass, and function appeared to be
      normal, the patients with diabetes had significantly lower phosphocreatine
      (PCr)/ATP ratios, at 1.50+/-0.11, than the healthy volunteers, at 2.30+/-0.12.
      The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free
      fatty acid concentrations. Although skeletal muscle energetics and pH were normal
      at rest, PCr loss and pH decrease were significantly faster during exercise in
      the patients with diabetes, who had lower exercise tolerance. After exercise, PCr
      recovery was slower in the patients with diabetes and correlated with tissue
      reoxygenation times. The exercise times correlated negatively with the
      deoxygenation rates and the hemoglobin (Hb)A1c levels and the reoxygenation times
      correlated positively with the HbA1c levels. CONCLUSIONS: Type 2 diabetic
      patients with apparently normal cardiac function have impaired myocardial and
      skeletal muscle energy metabolism related to changes in circulating metabolic
      substrates.

PMID- 12810609
TI  - Enhanced lipid peroxidation and platelet activation in the early phase of type 1
      diabetes mellitus: role of interleukin-6 and disease duration.
AB  - BACKGROUND: To investigate early events possibly related to the development of
      diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso
      PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different
      stages of type 1 diabetes (T1DM) and whether it correlates with the rate of
      thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We
      also investigated the relationship between inflammatory markers and F2
      isoprostane formation in this setting. METHODS AND RESULTS: A cross-sectional
      study was performed in 23 insulin-treated patients aged <18 years with new-onset
      T1DM (<or=6 weeks, group A), matched for age and gender with 23 patients with
      stable disease (>1 year, group B). Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2
      were measured in all patients and in age- and gender-matched controls.
      Circulating interleukin-6 (IL-6), tumor necrosis factor-alpha, and C-reactive
      protein were also determined as markers of the inflammatory response. Fifteen of
      the 23 children in group A were reexamined after 12 months. Compared with either
      controls or group B, diabetic children in group A showed significantly higher
      levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, IL-6, tumor necrosis factor-alpha,
      and C-reactive protein. Statistically significant correlations between IL-6 and
      both 8-iso-PGF2alpha (r=0.63, P<0.001) and 11-dehydro-TXB2 (r=0.51, P<0.01) were
      observed. The 15 patients reexamined after 1 year showed a significant reduction
      in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively),
      consistent with reduced levels of IL-6 and tumor necrosis factor-alpha.
      CONCLUSIONS: These results demonstrate that enhanced lipid peroxidation and
      platelet activation represent early events in T1DM that are possibly related to
      an acute inflammatory response. These noninvasive indexes may help in further
      examining T1DM pathophysiology and monitoring pharmacological interventions to
      interfere with disease development and progression.

PMID- 12810611
TI  - Determination of the upper limit of vulnerability using implantable cardioverter
      defibrillator electrograms.
AB  - BACKGROUND: The upper limit of vulnerability (ULV) correlates with the
      defibrillation threshold and can be determined with 1 episode of ventricular
      fibrillation (VF). To automate the ULV in an implantable cardioverter
      defibrillator (ICD), the most vulnerable intervals must be identified from an ICD
      electrogram rather than the latest-peaking surface T wave (Tpeak). We
      hypothesized that the recovery time (TR), defined as the maximum derivative
      (dV/dt) of the T wave of the shock electrogram, correlates with the most
      vulnerable intervals. METHODS AND RESULTS: We determined ULV, defibrillation
      threshold, and the most vulnerable intervals in 25 patients at ICD implantation.
      The ULV was the weakest T-wave shock that did not induce VF. The most vulnerable
      intervals were the ones associated with the strongest shocks that induced VF.
      Telemetered shock electrograms were stored on digital tape and differentiated
      offline to measure TR. Tpeak and TR were highly correlated (Tpeak-TR=-2+/-11 ms;
      rho=0.80, P<0.001). At least 1 most vulnerable interval timed between -20 ms and
      +20 ms relative to Tpeak in all patients and between -40 ms and +20 ms relative
      to TR in 96% of patients. CONCLUSIONS: The recovery time of shock electrograms
      provides accurate information about global repolarization. TR closely
      approximates Tpeak. The ULV method may be automated in an ICD by timing T-wave
      shocks relative to TR.

PMID- 12810610
TI  - Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1
      (LOX1) gene and the risk of coronary artery disease.
AB  - BACKGROUND: We examined the association of 3 polymorphisms in the lectin-like
      oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the
      Women's Ischemia Syndrome Evaluation (WISE) study population. METHODS AND
      RESULTS: The WISE sample comprised 589 white and 122 black women who underwent
      angiography for suspected ischemia. The sample was divided into 3 groups: <20%
      stenosis (38.7%), 20% to 49% stenosis (24.9%), and >or=50% stenosis (35.3%). The
      three LOX1 polymorphisms (intron 4/G-->A, intron 5/T-->G, and 3' UTR/T-->C) were
      in linkage disequilibrium and thus behaved as a single polymorphism. The
      frequency of the 3'UTR/T allele was significantly higher in whites than blacks
      (49% versus 19%; P<0.0001). Among white women, the frequency of the 3'UTR/T
      allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and
      79.2% in the <20%, 20% to 49%, and >or=50% stenosis groups, respectively (chi2
      trend=6.23; P=0.013). Logistic regression analyses indicated that APOE (odds
      ratio, 1.90; P=0.007) and LOX1 (odds ratio, 1.67; P=0.025) genotypes were
      independently associated with the risk of disease and that there was no
      interaction between the two genes. The 3'UTR/T allele carriers also had
      significantly higher IgG anti-oxLDL levels than individuals carrying the CC
      genotype (0.94+/-0.20 versus 0.86+/-0.16; P=0.032). Furthermore, our
      electrophoretic mobility shift assay data show that the 3'UTR polymorphic
      sequence affects the binding of a putative transcription factor in an allele
      specific manner. CONCLUSIONS: Our data suggest that common genetic variation in
      the LOX1 gene may be associated with the risk of coronary artery disease in white
      women.

PMID- 12810612
TI  - Increased expression of thrombospondin-1 in vessel wall of diabetic Zucker rat.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) expression in the vascular wall has been
      related to the development of atherosclerotic lesions and restenosis. TSP-1
      promotes the development of neointima and has recently been associated with
      atherogenesis at a genetic level. Because TSP-1 expression is responsive to
      glucose stimulation in mesangial cells, we hypothesized that glucose may
      stimulate its production by vascular cells. Thus, TSP-1 expression in the blood
      vessel wall may increase, providing a molecular link between diabetes and
      accelerated vascular lesion development. METHODS AND RESULTS: To determine
      whether the expression level of TSP-1 in vessel wall is increased in diabetes,
      aorta and carotid arteries of Zucker rats were used for immunostaining, Western
      blotting, and in situ RNA hybridization. A significant increase in TSP-1
      expression was found in the adventitia of blood vessels from diabetic rats.
      Consistent with the well-known antiangiogenic effect of TSP-1, the number of vasa
      vasorum was reduced in aortas from diabetic rats. In cultured endothelial cells,
      vascular smooth muscle cells, and fibroblasts, TSP-1 expression increased in
      response to glucose stimulation (>30-fold). After balloon catheter injury to
      carotid arteries, expression of TSP-1 protein and mRNA was higher at all time
      points in the vessels of diabetic rats. CONCLUSIONS: Increased expression of TSP
      1 in blood vessels in diabetes may represent a new link between diabetes,
      atherogenesis, and accelerated restenosis. This increase in TSP-1 production may
      be a direct response of vascular cells to glucose.

PMID- 12810613
TI  - Overexpression of the serotonin 5-HT2B receptor in heart leads to abnormal
      mitochondrial function and cardiac hypertrophy.
AB  - BACKGROUND: Identification of factors regulating myocardial structure and
      function is important to understand the pathogenesis of heart disease. We
      previously reported that 5-HT2B receptor ablation in mice leads to dilated
      cardiomyopathy. In this study, we investigated the pathological consequence of
      overexpressing 5-HT2B receptors in heart in vivo. METHODS AND RESULTS: We have
      generated transgenic mice overexpressing the Gq-coupled 5-HT2B receptor
      specifically in heart. We found that overexpression of 5-HT2B receptor in heart
      leads to ventricular hypertrophy as the result of increased cell number and size.
      Increased atrial natriuretic peptide and myosin heavy chain expression
      demonstrated activation of the molecular program for cardiac hypertrophy.
      Echocardiographic analysis indicated the presence of thickened ventricular free
      wall without alteration of the systolic function, showing that transgenic mice
      have compensated hypertrophy. Electron microscopic analysis revealed structural
      abnormalities including mitochondrial proliferation, as also manifested by
      histological staining. Transgenic mouse heart displayed a specific reduction in
      the expression levels of the adenine nucleotide translocator associated to
      increase in the succinate dehydrogenase and cytochrome C oxidase mitochondrial
      activities. CONCLUSIONS: Our results constitute the first genetic evidence that
      overexpression of the 5-HT2B receptor in the heart leads to compensated
      hypertrophic cardiomyopathy associated with proliferation of the mitochondria.
      This observation suggests a role for mitochondria in the hypertrophic signaling
      that is regulated by serotonin. These transgenic mice provide a new genetic model
      for hypertrophic heart disease.

PMID- 12810614
TI  - D-dimer, inflammatory markers, and lower extremity functioning in patients with
      and without peripheral arterial disease.
AB  - BACKGROUND: We determined whether higher levels of D-dimer, C-reactive protein
      (CRP), fibrinogen, and serum amyloid A are associated independently with
      functional impairment in patients with and without peripheral arterial disease
      (PAD). METHODS AND RESULTS: Participants were 370 men and women with PAD (ankle
      brachial index <0.90) and 231 without PAD. Functional outcomes were 6-minute walk
      distance and 4-meter walking velocity. A summary performance score combined
      performance in walking speed, standing balance, and time for 5 repeated chair
      rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age,
      sex, ankle brachial index, comorbidities, and other potential mediators and
      confounders, D-dimer levels were associated independently and inversely with
      performance on all 3 functional measures in the entire cohort and among patients
      with and without PAD, respectively. Adjusting for known and potential
      confounders, CRP levels were associated independently with 6-minute walk distance
      and the summary performance score among participants with PAD. No significant
      associations were observed between CRP and the functional measures among
      participants without PAD. Fibrinogen and SAA levels were not associated
      independently with the functional measures. CONCLUSIONS: Higher D-dimer levels
      are associated with poorer functioning among individuals with and without PAD.
      Higher CRP levels were associated with poorer 6-minute walk performance and a
      lower summary performance score among participants with PAD but not among those
      without PAD. Additional study is needed to determine whether D-dimer and CRP are
      involved in the pathophysiology of functional impairment or whether they are
      simply sensitive markers of the extent of systemic atherosclerosis.

PMID- 12810615
TI  - Regular physical activity improves endothelial function in patients with coronary
      artery disease by increasing phosphorylation of endothelial nitric oxide
      synthase.
AB  - BACKGROUND: In stable coronary artery disease (CAD), exercise training has well
      documented positive effects on arterial endothelial function. NO derived from
      endothelial NO synthase (eNOS) is regarded as a protective factor against
      atherosclerosis. The aim of the present study was to investigate the effects of
      exercise training on the endothelial function in relation to the expression of
      eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery
      (LIMA) of patients with stable CAD. METHODS AND RESULTS: In 17 training patients
      (T) and 18 control patients (C), endothelium-dependent vasodilation and average
      peak flow velocity (APV) in response to acetylcholine were measured invasively at
      study beginning and after 4 weeks in the LIMA. In LIMA tissue sampled during
      bypass surgery, eNOS expression and content of pospho-eNOS-Ser1177, Akt, and
      phospho-Akt were determined by Western blot and quantitative reverse
      transcriptase-polymerase chain reaction. After exercise training, LIMA APV in
      response to acetylcholine was increased by 56+/-8% (from +48+/-8% at beginning to
      +104+/-11% after 4 weeks, P<0.001). Patients in T had a 2-fold higher eNOS
      protein expression (T 1.0+/-0.7 versus C 0.5+/-0.3 arbitrary units, P<0.05) and 4
      fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium (1.2+/-0.9
      versus 0.3+/-0.2 arbitrary units, P<0.01). A linear correlation was confirmed
      between Akt phosphorylation and phospho-eNOS levels (R=0.80, P<0.05) and between
      phospho-eNOS and Delta APV (R=0.59, P<0.05). CONCLUSIONS: Exercise training in
      stable CAD leads to an improved agonist-mediated endothelium-dependent
      vasodilatory capacity. The change in acetylcholine-induced vasodilatation was
      closely related to a shear stress-induced/Akt-dependent phosphorylation of eNOS
      on Ser1177.

PMID- 12810616
TI  - Estrogen increases bone marrow-derived endothelial progenitor cell production and
      diminishes neointima formation.
AB  - BACKGROUND: Estrogens improve endothelial function and accelerate
      reendothelialization after vascular injury via largely unknown mechanisms. Bone
      marrow-derived endothelial progenitor cells (EPCs) are thought to positively
      influence endothelialization, vascular repair, and angiogenesis. METHODS AND
      RESULTS: In mice subjected to sham operation, ovariectomy, or ovariectomy and
      estrogen replacement treatment, estrogen deficiency significantly decreased EPCs
      circulating in the peripheral blood and residing in the bone marrow, as well as
      EPCs that were in vitro expanded from spleen-derived mononuclear cells. These
      effects were completely prevented by estrogen replacement. Human women with
      increased estrogen plasma concentrations also displayed profoundly increased
      levels of circulating EPCs. Estrogens increase EPC numbers through a decreased
      apoptosis rate, which is mediated via a caspase-8-dependent pathway. Estrogen
      deficiency increased neointima formation after carotid artery injury in mice, but
      this effect was diminished by estrogen replacement therapy. In mice transplanted
      with green fluorescent protein-positive bone marrow, reendothelialization of
      injured vessel segments by bone marrow-derived cells was decreased during
      estrogen deficiency and increased in response to estrogen treatment. CONCLUSIONS:
      Estrogens increase numbers of EPCs by antiapoptotic effects leading to
      accelerated vascular repair and decreased neointima formation.

PMID- 12810617
TI  - Elasticity imaging of atheroma with transcutaneous ultrasound: preliminary study.
AB  - BACKGROUND: Knowledge of the physical properties of atherosclerotic plaque is
      essential when evaluating its vulnerability in a clinical setting. Such
      knowledge, however, is still difficult to obtain with the various approaches
      developed to date. METHODS AND RESULTS: This article describes a noninvasive
      method for evaluating the regional elasticity (the elastic modulus in the
      circumferential direction) of tissue surrounding atherosclerotic plaque in which
      a novel phased tracking method is applied to measure minute changes in thickness
      of each of the multiple layers of the arterial wall during one heartbeat. By
      comparing the pathological findings with the distribution of elasticity, average
      elasticity of lipid and that of a mixture of smooth muscle and collagen fiber can
      be determined. On the basis of these reference parameters, each point is
      statistically categorized as lipid, mixture, or other. Thus, the plaque is
      electronically stained using transcutaneous ultrasound. By applying the method to
      the common carotid arteries, the presence of thin collagen fiber was clarified
      along the arterial axis for normal subjects, whereas soft inclusion of lipid was
      found for every plaque in subjects with hyperlipidemia. CONCLUSIONS: This novel
      method offers potential as a diagnostic technique for detection of plaque
      vulnerability with high spatial resolution.

PMID- 12810618
TI  - 10 years of mouse cancer modifier loci: human relevance.
AB  - About 10 years have elapsed since the first whole-genome scanning studies in the
      mouse to identify loci that affect susceptibility or resistance to tumorigenesis.
      In that time, >100 cancer modifiers have been mapped, and four strong candidate
      genes have been identified. Cancer modifier loci affect almost all types of mouse
      tumorigenesis, with some loci acting on the entire tumorigenic process, whereas
      others act on specific stages, e.g., tumor initiation or tumor
      growth/progression. Present evidence indicates that the effects of cancer
      modifier loci are tissue-specific and restricted to tumor cells. However, a
      subset of such loci may be involved in different types of tumors, and several
      chromosomal regions show significant clustering of cancer modifier loci. Human
      homologues of mouse cancer modifier loci most likely exist and play a role in the
      risk of sporadic cancer, although present experimental evidence for this
      possibility is sparse. Mouse cancer modifier loci might serve as the basis for
      understanding the genetic and biochemical mechanisms of polygenic inheritance of
      cancer predisposition/resistance. Identification of homologous cancer modifier
      loci in humans might, in turn, provide a step toward the development of
      diagnostic, preventive, and therapeutic strategies that target these loci.

PMID- 12810619
TI  - Delayed in vivo disease progression is associated with high proportions of CD45+
      myeloma cells in the 5T2MM murine model.
AB  - Both CD45(+) and CD45(-) multiple myeloma (MM) cells are observed in the bone
      marrow (BM) of MM patients; however, their impact on the outcome of the disease
      is unknown. Most (92%) of the mice injected with murine 5T2MM cells develop
      myeloma in 10-12 weeks and show hind leg paralysis at the end phase of the
      disease. In the end stage 5T2MM cells are predominantly CD45(-), in analogy to
      the common human situation. Herein we report that 8% of the mice have a delayed
      tumor progression (14-24 weeks) with a complete different feature in the end
      stage of the disease. These animals had typically a bowed back and never got
      paralyzed. The MM cells in the BM of these mice were predominantly CD45(+). These
      data indicate that CD45 subsets are associated with the final outcome of myeloma
      disease.

PMID- 12810620
TI  - p21Cip1 nullizygosity increases tumor metastasis in irradiated mice.
AB  - p21(Cip1) is a cyclin-dependent kinase inhibitor whose abundance increases in
      cells exposed to radiation or other DNA-damaging agents. Such increases activate
      a G1 checkpoint, which allows time for DNA repair before S phase entry. By
      inhibiting cell cycle progression, p21(Cip1) potentially suppresses
      tumorigenesis, and in support, we show that p21(Cip1) heterozygous and
      nullizygous mice develop more tumors than do wild-type mice when exposed to a
      single dose of gamma-irradiation. Importantly, we also show that p21(Cip1)
      nullizygosity increases the incidence of metastatic tumors in irradiated mice. We
      suggest that p21(Cip1) is haploinsufficient for tumor suppression and functions
      as an antimetastatic agent.

PMID- 12810621
TI  - Lytic bone lesions in human neuroblastoma xenograft involve osteoclast
      recruitment and are inhibited by bisphosphonate.
AB  - Neuroblastoma is the second most common solid tumor in childhood and frequently
      metastasizes to the bone marrow and the bone matrix. The mechanism involved in
      bone metastasis and destruction in neuroblastoma is poorly understood. Using a
      model of bone invasion in immunodeficient mice, we demonstrated that
      neuroblastoma cells recruited osteoclasts to generate osteolytic lesions and
      invade the bone matrix. In further support of a contributory role for osteoclasts
      in neuroblastoma bone invasion, we demonstrated that treatment with the
      bisphosphonate compound, ibandronate, significantly delayed the progression of
      osteolytic lesions. The data suggest that bisphosphonates may be clinically
      effective in the treatment of bone metastases in neuroblastoma.

PMID- 12810622
TI  - Cyclooxygenase-2 expression and effect of celecoxib in gastric adenomas of
      trefoil factor 1-deficient mice.
AB  - Expression of cyclooxygenase-2 (Cox-2) is elevated in gastric adenocarcinomas and
      precursor lesions leading to this disease. Mice deficient for trefoil factor 1
      (TFF1) develop a pyloric adenoma with full penetrance. Because inhibition of Cox
      2 suppresses tumor growth in several animal models, we studied expression of Cox
      2 and effect of a selective Cox-2 inhibitor celecoxib in gastrointestinal tissues
      of the TFF1-deficient mice. Cox-2 mRNA and protein were strongly expressed in the
      pyloric adenomas of the TFF1(-/-) mice as detected by in situ hybridization and
      immunohistochemistry. Nonneoplastic gastrointestinal tissues of wild-type or
      TFF1(-/-) mice expressed low or nondetectable levels of Cox-2. Celecoxib (1600
      ppm p.o. for 3 months) caused ulceration and inflammation of the adenoma in all
      treated TFF1(-/-) mice (n = 7). This effect of the drug was adenoma specific,
      because no histological alterations were observed in the non-neoplastic gastric
      or intestinal tissues in the TFF1(-/-) or wild-type mice receiving the drug
      treatment. All untreated TFF1(-/-) mice had an adenoma (n = 7), but none
      demonstrated the combination of ulceration and inflammation. Our data show that
      Cox-2 is expressed in gastric adenomas of the TFF1(-/-) mice and suggest that
      inhibition of Cox-2 disturbs the integrity of the adenoma by promoting ulceration
      and inflammation. These findings support the effort to initiate clinical studies
      to investigate the effect of Cox-2 inhibitors as a chemotherapeutic modality for
      dysplasias of the stomach.

PMID- 12810623
TI  - Inhibition of the development of metastatic squamous cell carcinoma in protein
      kinase C epsilon transgenic mice by alpha-difluoromethylornithine accompanied by
      marked hair follicle degeneration and hair loss.
AB  - The role of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated polyamine
      biosynthesis in the development of metastatic squamous cell carcinoma (mSCC) in
      protein kinase C epsilon (PKC epsilon) transgenic mice was determined. TPA
      treatment induced epidermal ornithine decarboxylase (ODC) activity and putrescine
      levels approximately 3-4-fold more in PKC epsilon transgenic mice than their wild
      type littermates. Development of mSCC by the 7,12-dimethylbenz(a)anthracene (100
      nmol)-TPA (5 nmol) protocol in PKC epsilon transgenic mice was completely
      prevented by administration of the suicide inhibitor of ODC alpha
      difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA
      promotion. However, DFMO treatment led to marked hair loss in PKC epsilon
      transgenic mice. DFMO treatment-associated hair loss in PKC epsilon transgenic
      mice was accompanied by a decrease in the number of intact hair follicles. These
      results indicate that TPA-induced ODC activity and the resultant accumulation of
      putrescine in PKC epsilon transgenic mice are linked to growth and maintenance of
      hair follicles, and the development of mSCC. Severe hair loss observed in PKC
      epsilon transgenic mice on DFMO during skin tumor promotion has not been reported
      before in the prevention of cancer in other animal models or in human cancer
      prevention trials.

PMID- 12810624
TI  - Involvement of PEG10 in human hepatocellular carcinogenesis through interaction
      with SIAH1.
AB  - Through a genome-wide cDNA microarray, we identified that the paternally
      expressed gene 10 (PEG10) was highly expressed in a great majority of
      hepatocellular carcinomas, although its expression was absent in normal liver
      cells. Exogenous expression of PEG10 conferred oncogenic activity and
      transfection of hepatoma cells with antisense S-oligonucleotides suppressing
      PEG10 resulted in their growth inhibition. Additional experiments revealed that
      PEG10 protein associated with SIAH1, a mediator of apoptosis, and that
      overexpression of PEG10 decreased the cell death mediated by SIAH1. These
      findings suggested that development of drug(s) inhibiting PEG10 activity could be
      a novel approach for the treatment of hepatocellular carcinomas.

PMID- 12810625
TI  - Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell
      cycle checkpoint.
AB  - Cell cycle checkpoints play a central role in genomic stability. The human DNA
      topoisomerase II-binding protein 1 (TopBP1) protein contains eight BRCA1 COOH
      terminus motifs and shares similarities with Cut5, a yeast checkpoint Rad
      protein. TopBP1 also shares many features with BRCA1. We report that, when
      expression of TopBP1 protein is inhibited in BRCA1 mutant cells, mimicking a
      TopBP1, BRCA1 double-negative condition, the G(2)-M checkpoint is strongly
      abrogated and apoptosis is increased after ionizing radiation. However, a BRCA1
      negative or a TopBP1-negative background resulted in only partial abrogation of
      the G(2)-M checkpoint. The BRCA1 mutant and TopBP1-reduced condition specifically
      destroys regulation of the Chk1 kinase but not the Chk2 kinase, suggesting
      involvement in the ataxia telangiectasia-related pathway. These results indicate
      that both TopBP1 and BRCA1 specifically regulate the G(2)-M checkpoint, partially
      compensating each function.

PMID- 12810626
TI  - Suppression of Bcl-xL deamidation in human hepatocellular carcinomas.
AB  - Bcl-xL is an antiapoptotic member of the Bcl-2 family, which inhibits apoptosis
      initiated by various cellular stresses, and has a pivotal role in the survival of
      tumor cells. Researchers have previously observed elevated expression of Bcl-xL
      in some human malignancies. In this study, we present evidence that human Bcl-xL
      is deamidated at asparagines 52 and 66 and that the rate of Bcl-xL deamidation is
      significantly lower in hepatocellular carcinomas than in normal or adjacent
      nontumor liver tissues. Because protein deamidation of Bcl-xL imports a complete
      "loss of function" of this antiapoptotic molecule, the present study indicates
      that tumor cells may acquire resistance to apoptosis and a survival advantage by
      suppressing deamidation as well as by increasing the expression of Bcl-xL. Thus,
      suppression of Bcl-xL deamidation may play a critical role in the regulation of
      cell death by apoptosis.

PMID- 12810627
TI  - Inhibition of early tumor growth requires J alpha 18-positive (natural killer T)
      cells.
AB  - The role of natural killer T (NKT) cells in the immune response to tumor cells
      has been largely unexplored. As a model of adoptive tumor immunotherapy, cells
      from the draining lymph nodes of mice immunized with a tumor-specific or
      irrelevant antigen were transferred to naive recipients with established tumor.
      Inhibition of early tumor growth (day 4) required the transfer of both CD8(+) and
      J alpha 18(+) (NKT) cells from immunized animals without regard to immunogen. In
      contrast, CD8(+) cells, but not J alpha 18(+) cells, were necessary for the
      inhibition of late tumor growth (day 8). Thus, the developing tumor changes in
      sensitivity to NKT-mediated events and the role for NKT cells cannot be replaced
      by the presence of tumor-specific cells during early tumor growth. This suggests
      that recruitment/activation of J alpha 18(+) NKT cells is an important
      consideration during the immune therapy of early stage tumors.

PMID- 12810628
TI  - BRAF as a melanoma susceptibility candidate gene?
AB  - A high frequency of activating BRAF somatic mutations have been identified
      recently in malignant melanoma and nevi indicating that BRAF activation could be
      an early and critical step in the initiation of melanocytic neoplasia. To
      determine whether BRAF mutations could be an earlier event occurring at the
      germline level, we screened the entire BRAF coding region for germline mutations
      in 80 independent melanoma-prone families or patients with multiple primary
      melanoma without a familial history. We identified 13 BRAF variants, 4 of which
      were silent mutations in coding regions and 9 nucleotide substitutions in
      introns. None of these BRAF variants segregated with melanoma in the 11 melanoma
      families studied. Moreover, there was no significant difference in the frequency
      of heterozygotes for BRAF variants between melanoma cases and controls when they
      were compared. Our data suggest that BRAF is unlikely to be a melanoma
      susceptibility gene.

PMID- 12810629
TI  - An interleukin-6 gene promoter polymorphism influences the biological phenotype
      of ovarian cancer.
AB  - Interleukin (IL)-6 is known to be involved in the pathogenesis of ovarian cancer.
      We investigated a common G/C polymorphism at position -174 of the IL-6 gene (IL6)
      promoter in 121 patients with ovarian cancer using pyrosequencing. Presence of at
      least one mutant allele was associated with early tumor stage as well as an
      expanded length of disease-free (DFS) and overall survival with a dose-dependent
      effect regarding the carriage of 0, 1, and 2 alleles. In a multivariate Cox
      regression model incorporating tumor stage and residual tumor mass, presence of
      the -174 C allele of IL6 was the best predictor of DFS. We conclude that the
      mutant -174 C allele of IL6 influences the biological phenotype of ovarian cancer
      because it is associated with early stage and improved DFS and overall survival.

PMID- 12810630
TI  - Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and
      cancer cell invasion.
AB  - Histone deacetylase (HDAC) inhibitors are known to exert antimetastatic and
      antiangiogenic activity in vitro and in vivo. RECK is a membrane-anchored
      glycoprotein that negatively regulates matrix metalloproteinases (MMPs) and
      inhibits tumor metastasis and angiogenesis. In this study, we test the
      possibility that HDAC inhibitor may increase RECK expression to inhibit MMP
      activation and cancer cell invasion. Our results showed that trichostatin A (TSA)
      up-regulated RECK via transcriptional activation in CL-1 human lung cancer cells.
      Flow cytometric analysis demonstrated that RECK protein on cell surface was
      increased after treatment of TSA. Moreover, up-regulation of RECK expression by
      TSA attenuated MMP-2 activity. To explore whether HDAC inhibitor-induced
      inhibition of MMP-2 activation is indeed mediated via RECK, we used small
      interference RNA (siRNA) to block RECK expression and found that inhibition of
      RECK by siRNA abolished the inhibitory effect of TSA on MMP-2 activation. In
      addition, TSA suppressed the invasive ability of CL-1 cells. Taken together, this
      study reveals a novel mechanism by which HDAC inhibitors suppress tumor invasion
      and provides a new strategy for cancer therapy.

PMID- 12810631
TI  - Adenovirus with insertion-mutated E1A selectively propagates in liver cancer
      cells and destroys tumors in vivo.
AB  - The adenovirus E1A proteins are involved in the transcriptional activation of
      viral and cellular genes needed for controlling cell cycle and virus replication.
      Undifferentiated embryonic carcinoma cells have the ability to produce an E1A
      like activity that can induce the expression of E1A-targeted adenoviral and
      cellular genes in the absence of the E1A products. Differentiated embryonic
      carcinoma cells lose the ability to produce the E1A-like activity. In this study,
      we investigated the E1A-like activity in cancer cells with an adenovirus having a
      mutated E1a gene. The mutation is generated by the insertion of a large DNA
      fragment in the E1a gene and interrupts the COOH-terminal region of both the E1A
      12S and 13S proteins. The E1a-mutated virus can efficiently replicate in HepG2
      and Hep3B liver cancer cells and produce high titers of virus. Replication of the
      E1a-mutated virus inhibits tumor formation and destroys tumors in vivo. The
      results obtained in this study imply that cancer cells may produce an E1A-like
      activity to support the selective replication of mutated virus in cancer cells.
      In addition, we found that although the E1a-mutated virus could not replicate in
      Huh1.cl2 liver cells, the viral DNA could amplify in the cells. This result
      suggests that replication of adenoviral DNA is necessary, but not sufficient, for
      generating infectious viral progeny and destroying tumor cells.

PMID- 12810632
TI  - NUP98 is fused to adducin 3 in a patient with T-cell acute lymphoblastic leukemia
      and myeloid markers, with a new translocation t(10;11)(q25;p15).
AB  - The nucleoporin 98 gene (NUP98) has been reported to be fused to 13 partner genes
      in hematological malignancies with 11p15 translocations. Twelve of them have been
      identified in patients with myeloid neoplasias and only 1, RAP1GDS1 (4q21), is
      fused with NUP98 in five patients with T-cell acute lymphoblastic leukemia (T
      ALL). Three of these patients coexpressed T and myeloid markers, suggesting the
      specific association of t(4;11)(q21;p15) with a subset of T-ALL originating from
      an early progenitor, which has the potential to express mature T-cell antigens as
      well as myeloid markers. We describe here a new NUP98 partner involved in a
      t(10;11)(q25;p15) in a patient with acute biphenotypic leukemia, showing
      coexpression of mature T and myeloid markers. The gene involved, located in
      10q25, was identified as ADD3 using 3'-RACE. ADD3 codes for the ubiquitous
      expressed subunit gamma of the adducin protein, and it seems to play an important
      role in the skeletal organization of the cell membrane. Both NUP98-ADD3 and ADD3
      NUP98 fusion transcripts are expressed in the patient. This is the second partner
      of NUP98 described in T-ALL. Adducin shares with the product of RAP1GDS1, and
      with all of the nonhomeobox NUP98 partners, the presence of a region with
      significant probability of adopting a coiled-coil conformation. This region is
      always retained in the fusion transcript with the NH(2) terminus FG repeats of
      NUP98, suggesting an important role in the mechanism of leukemogenesis.

PMID- 12810633
TI  - P-glycoprotein, expressed in multidrug resistant cells, is not responsible for
      alterations in membrane fluidity or membrane potential.
AB  - Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1 gene
      product, can lead to MDR in tumors. However, the physiological role of P-gp in
      normal tissues is not well understood. Previous studies on multidrug-resistant
      cells have suggested changes in membrane fluidity and membrane potential
      associated with P-gp expression, but interpretation of these studies is
      difficult, because most experimental cells have been selected for long periods in
      the presence of cytotoxic drugs and may have other host alterations. Therefore,
      we created two cell lines in which a transfected human MDR1 cDNA is repressed by
      tetracycline and induced in the absence of tetracycline. One cell line was
      derived from a mouse embryonic fibroblast cultured from a double (mdr1a/1b)
      knockout mouse, and the other was from a human HeLa cell line. Analysis of the
      kinetics of expression of P-gp showed that the mRNA had a half-life of
      approximately 4 h, and the protein had a half-life of approximately 16 h. P-gp
      cell surface expression (measured with monoclonal antibody MRK-16) and P-gp
      function (measured with a fluorescent substrate, rhodamine 123) was characterized
      by using fluorescence-activated cell sorting. No differences in membrane
      potential using the fluorescent probe oxonol or in membrane "fluidity" using
      fluorescent anisotropy probe or electron spin resonance probe were observed in
      the tet-repressible P-gp-expressing cells. In contrast, several drug-selected
      cells that express P-gp showed an increase in membrane fluidity and membrane
      potential. These results suggest that expression of P-gp per se has little effect
      on membrane fluidity or membrane potential, and it does not have H(+) pump
      activity. The changes in these parameters observed in drug-selected cells must
      reflect other host adaptations to drug selection.

PMID- 12810634
TI  - Class I alcohol dehydrogenase is highly expressed in normal human mammary
      epithelium but not in invasive breast cancer: implications for breast
      carcinogenesis.
AB  - Detoxification of ethanol can contribute to oxidative cellular and DNA damage
      and, thereby, to carcinogenesis. The potential relevance of this to breast
      carcinogenesis is suggested by evidence that alcohol consumption is a risk factor
      for breast cancer. It is, however, not known whether ethanol can be metabolized
      in breast parenchyma. The goal of this study was to determine whether class I
      and/or IV alcohol dehydrogenase (ADH), medium chain ADHs that can catalyze
      oxidation of ethanol, are expressed in human breast parenchyma. Normal and
      neoplastic human breast tissue specimens were examined for class I and IV ADH
      mRNA by reverse transcription-PCR, for protein by immunocytochemistry and Western
      analysis, and for their potential to catalyze NAD(+)-dependent oxidation of
      ethanol. Together, the findings provide evidence that: (a) class I ADH is the
      medium-chain ADH that is expressed in human breast parenchyma, specifically in
      the mammary epithelium; (b) human breast parenchyma can support ADH-mediated
      oxidation of ethanol; and (c) the expression of class I ADH is dramatically
      reduced or abrogated in invasive breast cancers. Expression of class I ADH in
      normal human breast parenchyma was confirmed by probing a multiple human tissue
      polyA(+)RNA. The unexpected finding of virtual abrogation of expression of class
      I ADH in invasive breast cancer suggests that the enzyme has some "tumor
      suppressor" function in the mammary epithelium. The one property of class I ADH
      fitting this designation is its potential to catalyze the oxidation of the
      micronutrient/prohormone retinol to retinal, the first step in the biosynthesis
      of retinoic acid, the principal known mediator of the actions of retinoids
      important for maintaining epithelia in a differentiated state.

PMID- 12810635
TI  - Multiple promoters of catechol-O-methyltransferase gene are selectively
      inactivated by CpG hypermethylation in endometrial cancer.
AB  - Catechol-O-methyltransferase (COMT) plays an important role in estrogen-induced
      cancers because COMT inactivates catechol estrogens that have cancer-promoting
      activities. Two promoters control the expression of human COMT isoforms: membrane
      bound COMT (MB-COMT) and soluble COMT (S-COMT). We hypothesize that inactivation
      of MB-COMT and S-COMT is important in understanding the pathogenesis of
      endometrial cancer. To test this hypothesis, we investigated the methylation
      status and expression of two COMT isoforms in 4 endometrial cancer cell lines, 60
      endometrial cancer tissues, 10 normal endometrium tissues from normal healthy
      controls, and 32 pairs of cancerous and normal endometrial samples from the same
      patients using methylation-specific PCR, methylation-specific sequencing, reverse
      transcription-PCR, and 5'-rapid amplification of cDNA ends. The results of this
      study clearly demonstrate that MB-COMT was inactivated and methylated, although S
      COMT was activated and unmethylated in all endometrial cancer cell lines. The 5
      aza-2'-deoxycytidine treatment restored MB-COMT expression in all cell lines. The
      promoter for MB-COMT was methylated in 47 of 60 cancer tissues but was
      unmethylated in endometrial tissues from cases without cancer. The promoter for S
      COMT was unmethylated in all endometrial cancerous and normal tissues. The CpG
      methylation density at the MB-COMT promoter was significantly higher in cancer
      tissues (a mean of 79.1% of the 19 CpG sites; range, 69-94%) than in adjacent
      normal tissues (a mean of 8.7% of the 19 CpG sites; range, 3-14%). In summary,
      these findings demonstrate that methylation of multiple promoters of the COMT
      gene can selectively inactivate MB-COMT and may contribute to endometrial
      carcinogenesis.

PMID- 12810636
TI  - Persistent oxidative stress in chromosomally unstable cells.
AB  - Past work using the human-hamster hybrid line GM10115 has demonstrated that
      exposure to a variety of DNA damaging agents can lead to the persistent
      destabilization of chromosomes. To gain insight into the potential biochemical
      mechanisms involved in perpetuating the unstable phenotype, groups of clones
      characterized as stable or unstable were analyzed for indications of oxidative
      stress. All of the clones were derived from single progenitor cells surviving
      exposure to ionizing radiation or chemicals. Compared with their stable
      counterparts, unstable clones possessed elevated levels of reactive oxygen
      species (ROS) as measured by their enhanced ability to oxidize fluorogenic dyes.
      Fluorescence automated cell sorting analysis indicated that unstable clones had
      significantly higher mean fluorescence signals of approximately 2-fold and
      approximately 1.25-fold, respectively, as derived from the dyes 5-(and-6)
      chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and dihydrorhodamine 123,
      respectively. To determine whether mitochondria might constitute a potential
      source of ROS, stable and unstable clones of cells were analyzed for
      mitochondrial content using nonyl acridine orange and function using rhodamine
      123. Fluorescence automated cell sorting data indicated that compared with stable
      clones, unstable clones possessed an elevated number (15% increase in mean nonyl
      acridine orange fluorescence) of dysfunctional mitochondria (27% decrease in mean
      rhodamine 123 fluorescence). Interestingly, the consequences of elevated ROS did
      not translate to an increase in oxidative base damage in nuclear DNA. Analysis of
      nine different base damage adducts by gas chromatography/mass spectrometry did
      not reveal significant differences between stable and unstable clones. The data
      suggest that the perpetuation of many of the abnormal phenotypes associated with
      genomic instability may be linked to a state of chronic oxidative stress derived
      in part from dysfunctional mitochondria.

PMID- 12810638
TI  - Quantitative correlation of serum levels and tumor expression of vascular
      endothelial growth factor in patients with hepatocellular carcinoma.
AB  - Recent studies have suggested that serum levels of vascular endothelial growth
      factor (VEGF) may provide useful prognostic information in patients with various
      types of cancers. However, there has been a debate on whether serum VEGF level is
      a true reflection of tumor angiogenic activity in cancer patients. This debate
      originates from the finding that most VEGF in the serum is released from
      platelets during clotting. It has been postulated that platelet may serve the
      role of storage for circulating VEGF derived from the tumors. We conducted a
      study to clarify whether the platelet load of VEGF in the circulation correlates
      with tumor expression of VEGF. We measured quantitatively the serum VEGF(165)
      levels and tumor cytosolic VEGF(165) concentration by an ELISA and tumor
      VEGF(165) mRNA by real-time quantitative reverse transcription-PCR in 60 patients
      with hepatocellular carcinoma. Serum VEGF(165) levels correlated significantly
      with platelet counts (r = 0.662, P < 0.001). When corrected for platelet count,
      serum VEGF(165)/platelet correlated significantly with tumor cytosolic VEGF(165)
      concentration (r = 0.447, P = 0.006), which in turn correlated with VEGF(165)
      mRNA expression in the tumors (r = 0.315, P = 0.020). Advancing tumor stage was
      associated with a significant increase in tumor cytosolic VEGF(165) concentration
      (P = 0.006), tumor VEGF(165) mRNA expression (P = 0.012), serum
      VEGF(165)/platelet (P = 0.001), and serum VEGF(165) levels (P = 0.003). In
      conclusion, our data showed that the platelet load of VEGF in the circulation
      correlated positively with tumor VEGF expression. This study provides strong
      evidence that supports the use of serum VEGF level as an indirect estimate of
      tumor VEGF expression.

PMID- 12810637
TI  - Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in
      carcinomas.
AB  - Chemotherapy and radiation therapy for cancer often have severe side effects that
      limit their efficacy. Glucocorticoids (GCs) are frequently used as cotreatment
      because they may have potent proapoptotic properties and reduce nausea,
      hyperemesis, and acute toxicity on normal tissue. In contrast to the proapoptotic
      effect of GCs in lymphoid cells, resistance toward cancer therapy-mediated
      apoptosis was induced in solid tumors of human cervix and lung carcinomas. Filter
      hybridization, expression data, as well as functional assays identified multiple
      core apoptosis molecules, which are regulated by GCs in a pro- or antiapoptotic
      manner. Both antiapoptotic genes such as FLIP and members of the Bcl-2 and IAP
      family as well as proapoptotic elements of the death receptor and mitochondrial
      apoptosis pathways were down-regulated in carcinomas resulting in a decreased
      activity of caspase-8, caspase-9, and caspase-3. In contrast, death receptor and
      mitochondrial apoptosis signaling as well as caspase activity was enhanced by
      dexamethasone in lymphoid cells. To restore apoptosis sensitivity in
      dexamethasone-treated carcinomas, caspase-8 and caspase-9 were transfected. This
      resensitized tumor cells in vitro and xenografts in vivo to cisplatin induced
      cell death. These data therefore raise concern about the widespread combined use
      of GCs with antineoplastic drugs or agents in the clinical management of cancer
      patients.

PMID- 12810639
TI  - Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1.
AB  - Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) catalyze the oxidative metabolism
      of 17 beta-estradiol (E2) to catechol estrogens (2-OHE2 and 4-OHE2) and estrogen
      quinones, which may lead to DNA damage. Catechol-O-methyltransferase catalyzes
      the methylation of catechol estrogens to methoxyestrogens (2-MeOE2, 2-OH-3-MeOE2,
      and 4-MeOE2), which simultaneously lowers the potential for DNA damage and
      increases the concentration of 2-MeOE2, an antiproliferative metabolite. In this
      study, we showed that CYP1A1 and CYP1B1 recognized as substrates both the parent
      hormone E2 and the methoxyestrogens. Using purified recombinant enzymes, we
      demonstrated that CYP1A1 and CYP1B1 O-demethylated the methoxyestrogens to
      catechol estrogens according to Michaelis-Menten kinetics. Both CYP1A1 and CYP1B1
      demethylated 2-MeOE2 and 2-OH-3-MeOE2 to 2-OHE2, whereas CYP1B1 additionally
      demethylated 4-MeOE2 to 4-OHE2. Because the P450-mediated oxidation of E2 and the
      O-demethylation of methoxyestrogens both yielded identical catechol estrogens as
      products, we used deuterated E2 (E2-d4), unlabeled methoxyestrogens, and gas
      chromatography/mass spectrometry to examine both reactions simultaneously.
      Kinetic analysis revealed that methoxyestrogens acted as noncompetitive
      inhibitors of E2 oxidation with K(i) ranging from 27 to 153 micro M. For both
      enzymes, the order of inhibition by methoxyestrogens was 2-OH-3-MeOE2 > or = 2
      MeOE2 > 4-MeOE2. Thus, methoxyestrogens exert feedback inhibition on CYP1A1- and
      CYP1B1-mediated oxidative estrogen metabolism, thereby reducing the potential for
      estrogen-induced DNA damage.

PMID- 12810640
TI  - Effects of dietary folate and alcohol intake on promoter methylation in sporadic
      colorectal cancer: the Netherlands cohort study on diet and cancer.
AB  - Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic
      changes such as regional DNA hypermethylation and global DNA hypomethylation.
      Epidemiological and animal studies suggest that aberrant DNA methylation is
      associated with low dietary folate intake, which is aggravated by high alcohol
      intake. The relationship between promoter methylation of genes involved in CRC
      carcinogenesis and folate and alcohol intake was investigated. Methylation of the
      APC-1A, p14(ARF), p16(INK4A), hMLH1, O(6)-MGMT, and RASSF1A promoters was studied
      using methylation-specific PCR in 122 sporadic CRCs, derived from patients with
      folate and alcohol intake at either the lower or the higher quintiles of the
      distribution. Overall, promoter hypermethylation frequencies observed were: 39%
      for APC; 33% for p14(ARF); 31% for p16(INK4A); 29% for hMLH1; 41% for O(6)-MGMT;
      and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter
      hypermethylation was higher in CRCs derived from patients with low folate/high
      alcohol intake (n = 61) when compared with CRCs from patients with high
      folate/low alcohol intake (n = 61), but the differences were not statistically
      significant. The number of CRCs with at least one gene methylated was higher
      (84%) in the low folate intake/high alcohol intake group when compared with the
      high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size
      limitations of this study, these data suggest that folate and alcohol intake may
      be associated with changes in promoter hypermethylation in CRC.

PMID- 12810641
TI  - Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis
      via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke
      exposed ferrets.
AB  - Higher intake of lycopene is related to a lower risk of lung cancer in human
      studies. Lung cancer risk is associated with higher plasma levels of insulin-like
      growth factor I (IGF-I) and/or lower levels of IGF-binding protein 3 (IGFBP-3).
      However, little is known regarding whether lycopene can inhibit cigarette smoke
      induced lung carcinogenesis through modulation of IGF-I/IGFBP-3, cell
      proliferation, and apoptosis. We investigated the effects of lycopene
      supplementation at a low dose (1.1 mg/kg/day, which is equivalent to an intake of
      15 mg/day in humans) and a high dose (4.3 mg/kg/day, which is equivalent to 60
      mg/day in humans) on plasma IGF-I/IGFBP-3 levels, histopathological changes,
      proliferating cellular nuclear antigen (PCNA) expression, BAD phosphorylation,
      and apoptosis (caspase 3 assay) in lungs of ferrets with or without cigarette
      smoke exposure for 9 weeks. We found that ferrets supplemented with lycopene and
      exposed to smoke had significantly higher plasma IGFBP-3 levels (P < 0.01) and a
      lower IGF-I/IGFBP-3 ratio (P < 0.01) than ferrets exposed to smoke alone. Both
      low- and high-dose lycopene supplementations substantially inhibited smoke
      induced squamous metaplasia and PCNA expression in the lungs of ferrets. No
      squamous metaplasia or PCNA overexpression were found in the lungs of control
      ferrets or those supplemented with lycopene alone. Furthermore, cigarette smoke
      exposure greatly increased BAD phosphorylation at both Ser(136) and Ser(112) and
      significantly decreased cleaved caspase 3 in the lungs of ferrets, as compared
      with controls. The elevated phosphorylation of BAD and down-regulated apoptosis
      induced by cigarette smoke in the lungs of ferrets was prevented by both low- and
      high-dose lycopene supplementations. Lycopene levels were increased in a dose
      dependent manner in both plasma and lungs of ferrets supplemented with lycopene
      alone. However, lycopene levels were markedly lower in both plasma and lungs of
      ferrets supplemented with lycopene and exposed to smoke. Furthermore, smoke
      exposure increased cis isomers (26% for 13-cis and 22% for 9-cis) of lycopene in
      the lungs of ferrets, compared with that of ferrets supplemented with lycopene
      alone (20% for 13-cis and 14% for 9-cis). In conclusion, lycopene may mediate its
      protective effects against smoke-induced lung carcinogenesis in ferrets through
      up-regulating IGFBP-3 and down-regulating phosphorylation of BAD, which promote
      apoptosis and inhibit cell proliferation.

PMID- 12810642
TI  - beta-Catenin regulates vascular endothelial growth factor expression in colon
      cancer.
AB  - To evaluate whether beta-catenin signaling has a role in the regulation of
      angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was
      analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of
      human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven
      consensus binding sites for beta-catenin/TCF. Analysis of laser capture
      microdissected human colon cancer tissue indicated a direct correlation between
      up-regulation of VEGF-A expression and adenomatous polyposis coli (APC)
      mutational status (activation of beta-catenin signaling) in primary tumors. In
      metastases, this correlation was not observed. Analysis by immunohistochemistry
      of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia
      gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in
      proximity to those cells expressing nuclear beta-catenin with a corresponding
      increase in vessel density. Transfection of normal colon epithelial cells with
      activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250
      300%. When colon cancer cells with elevated beta-catenin levels were treated with
      beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by
      more than 50%. Taken together, our observations indicate a close link between
      beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.

PMID- 12810643
TI  - Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific
      and efficient drug delivery to EGFR- and EGFRvIII-overexpressing tumor cells.
AB  - We hypothesized that immunoliposomes (ILs) that target epidermal growth factor
      receptor (EGFR) and/or its truncated variant EGFRvIII can be constructed to
      provide efficient intracellular drug delivery in tumor cells overexpressing these
      receptors. Monoclonal antibody fragments included Fab' fragments derived from
      C225, which binds both EGFR and EGFRvIII, or novel anti-EGFR scFv C10, which
      binds EGFR only. Monoclonal antibody fragments were covalently linked to
      liposomes containing various reporters or drugs. ILs were evaluated for specific
      binding, internalization, and cytotoxicity in EGFR/EGFRvIII-overexpressing cell
      lines in vitro. Flow cytometry and fluorescence microscopy showed that EGFR
      targeted ILs, but not nontargeted liposomes or irrelevant ILs, were efficiently
      bound and internalized by EGFR-overexpressing cells, including glioma cells (U
      87), carcinoma cells (A-431 and MDA-MB-468), and EGFRvIII stable transfectants
      (NR-6M). Furthermore, EGFR-targeted ILs did not bind to non-EGFR-overexpressing
      cells (MCF-7 and parental NR-6). ILs showed 3 orders of magnitude greater
      accumulation in NR-6-EGFRvIII stable transfectants versus parental NR-6 cells.
      Quantitative internalization studies indicated binding of EGFR-targeted ILs to
      target cells within 5 min, followed by intracellular accumulation beginning at 15
      min; total uptake reached approximately 13,000 ILs/cell. ILs were used to deliver
      cytotoxic drugs doxorubicin, vinorelbine, or methotrexate to EGFR/EGFRvIII
      overexpressing target cells in vitro. In each case, the IL agent was
      significantly more cytotoxic than the corresponding nontargeted liposomal drug in
      target cells, whereas it was equivalent in cells lacking EGFR/EGFRvIII
      overexpression. We conclude that EGFR-targeted ILs provide efficient and targeted
      delivery of anticancer drugs in cells overexpressing EGFR or EGFRvIII.

PMID- 12810644
TI  - Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal
      metastases from medulloblastoma.
AB  - Medulloblastoma (MB), the most common pediatric brain tumor, is a highly
      malignant disease with a 5-year survival rate of only 60%. Tumor cells invade
      surrounding tissue and disseminate through cerebral spinal fluid, making
      treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in
      tumor cells to support productive infection as an oncolytic virus. Here, we
      examined the ability of human reovirus to kill MB cells lines and surgical
      specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB
      cell lines tested (five of seven = 71.4%), two MB cell lines derived from
      spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three
      MB primary cultures derived from surgical specimens, were susceptible to reovirus
      infection. Reovirus was internalized and transcribed in both susceptible and
      resistant cell lines. However, viral protein synthesis was restricted to cell
      lines with higher levels of activated Ras, suggesting that Ras plays a critical
      role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model,
      we found that a single i.t. injection of reovirus dramatically prolonged survival
      compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating
      this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of
      reovirus, we again found prolonged survival and a dramatic reduction in spinal
      and leptomeningeal metastases (66.7% in control injections versus 0.0% in the
      live virus group). These data suggest that this oncolytic virus may be a
      potentially effective novel therapy against human MB. Its ability to reduce
      metastases to the spinal cord could allow a reduction in the dose/field of total
      neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral
      spinal fluid dissemination.

PMID- 12810645
TI  - Pharmacologically regulated production of targeted retrovirus from T cells for
      systemic antitumor gene therapy.
AB  - We aimed to use cell-based carriers to direct vector production to target sites
      for systemic therapy. We used T cells engineered to express a chimeric T cell
      receptor that can specifically recognize target cells expressing the tumor
      associated carcinoembryonic antigen (CEA). These T cells were modified to produce
      a retrovirus under tight pharmacological control using the rapamycin-inducible
      transcriptional regulatory system. The retroviral vectors produced were
      transcriptionally targeted to CEA-expressing target cells. We found that vector
      production and transgene expression from these T cells in vitro was dependent on
      pharmacological induction and expression of CEA in target cells, respectively.
      Mice bearing metastatic tumors that received cell carriers delivering the HSVtk
      gene demonstrated a significant increase in survival, but only in response to
      pharmacological induction of vector production. Interestingly, the therapeutic
      effect required the presence of the tumor-specific chimeric receptor on T cells.
      Further studies demonstrated that systemic delivery of tumor-specific T cells to
      mice bearing metastatic tumors caused recruitment of nonspecific T cells to the
      tumor site. We hypothesize that this enhanced targeting to tumor sites is
      responsible for the efficiency of T cell-mediated retroviral gene transfer and
      that this principle can be used to enhance systemic therapies using immune-cell
      carriers.

PMID- 12810646
TI  - A telomerase-dependent conditionally replicating adenovirus for selective
      treatment of cancer.
AB  - The catalytic component of human telomerase reverse transcriptase (hTERT) is not
      expressed in most primary somatic human cells, whereas the majority of cancer
      cells reactivate telomerase by transcriptional up-regulation of hTERT. Several
      studies demonstrated that the hTERT promoter can be used to restrict gene
      expression of E1-deleted replication defective adenoviral vectors to telomerase
      positive cancer cells. In this study, a conditionally replicating adenovirus
      (hTERT-Ad) expressing E1A genes under control of a 255-bp hTERT-promoter was
      constructed. Additionally, an internal ribosomal entry site-enhanced green
      fluorescent protein cassette was inserted downstream of the E1B locus to monitor
      viral replication in vivo. Adenoviral replication of hTERT-Ad and enhancement of
      enhanced green fluorescent protein expression could be observed in all
      investigated telomerase-positive tumor cell lines. In contrast, hTERT-Ad
      infection of telomerase-negative primary human hepatocytes did not result in
      significant replication. The capability of hTERT-Ad to induce cytopathic effects
      in tumor cells was comparable with that of adenovirus wild type and significantly
      higher compared with ONYX-015, regardless of the p53 status of the tumor cells.
      Single application of low-dose hTERT-Ad to tumor xenografts led to significant
      inhibition of tumor growth, confirming the potential therapeutic value of
      conditionally replicative adenoviral vectors. These in vivo experiments also
      revealed that hTERT-Ad-mediated oncolysis was more efficient than ONYX-015
      treatment. These results demonstrate that expression of E1A under transcriptional
      control of the hTERT promoter is sufficient for effective telomerase-dependent
      adenovirus replication as a promising perspective for the treatment of the
      majority of epithelial tumors.

PMID- 12810647
TI  - Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide
      analogues.
AB  - Inhibition of angiogenesis is currently perceived as one of the promising
      strategies in the treatment of cancer. The antiangiogenic property of thalidomide
      has inspired a second wave of research on this teratogenic drug. Previous studies
      from our group and others demonstrated that metabolites of thalidomide are
      responsible for the drug's pharmacological actions. On the basis of the
      structures of these metabolites, we synthesized 118 thalidomide analogues.
      Preliminary screening selected 7 of these 118 analogues for more extensive
      testing in the current study. In the rat aortic ring assay, all 4 analogues in
      the N-substituted class and 2 of the 3 analogues in the tetrafluorinated class
      significantly inhibited microvessel outgrowth at 12.5-200 microM. Thalidomide
      failed to block angiogenesis at similar concentrations. Subsequently, the effects
      of these analogues on human umbilical vein endothelial cell proliferation and
      tube formation were determined. Those analogues showing antiangiogenicity in the
      rat aortic ring assay also demonstrated antiproliferative action in human
      umbilical vein endothelial cells. Cell proliferation was not affected by
      thalidomide. Interestingly, all 7 analogues as well as thalidomide suppressed
      tube formation. Two tetrafluorinated analogues consistently showed the highest
      potency and efficacy in all three assays. The in vivo toxicity of representative
      analogues from each class was also evaluated. Taken together, our results support
      the further development and evaluation of novel thalidomide analogues as
      antiangiogenic agents.

PMID- 12810648
TI  - Assignment of 1H nuclear magnetic resonance visible polyunsaturated fatty acids
      in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced
      programmed cell death.
AB  - Polyunsaturated fatty acids (PUFAs), as detected by (1)H nuclear magnetic
      resonance (NMR) spectroscopy, accumulate into BT4C glioma during ganciclovir
      thymidine kinase gene therapy-induced programmed cell death (PCD). In this study,
      we have quantified the (1)H NMR visible lipids in vivo and characterized their
      biophysical and biochemical nature in these tumors during PCD both ex vivo and in
      vitro. Concentrations of (1)H NMR-detectable PUFAs increased 3-fold with pattern
      recognition identifying CH = CH and CH = CHCH(2)CH = CH as the most significant
      in monitoring the dynamics of PCD. The increase in PUFAs was equivalent to 70% of
      that in CH(2)CH(2)CH(2)-saturated lipid peak at 1.3 ppm. Ex vivo tumor samples,
      obtained from in situ funnel frozen tumors, showed very similar macromolecular
      peaks, as studied using high-resolution magic angle spinning (1)H NMR at 14.1 T,
      to those detected in vivo at 4.7 T. Line widths of lipid peaks were not
      influenced by the spin rate within the range of 1-9 kHz or temperature between
      277 and 293 K, showing high degree of (1)H NMR detection of these peaks in vivo.
      These biophysical results additionally corroborate the idea that cytoplasmic
      lipid vesicles are the source of (1)H NMR lipid signals. Two-dimensional (1)H NMR
      ex vivo and tumor lipid extracts in vitro showed that the PUFA signals are in the
      same chemical compounds and consist of largely 18:1 and 18:2 lipids. Furthermore,
      it is suggested that the (1)H NMR lipids detected during PCD arise from cell
      constituent breakdown products forming lipid vesicles into dying cells.

PMID- 12810649
TI  - Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to
      interleukin 12 and to tumor necrosis factor alpha.
AB  - The potent antitumor activity of certain cytokines is often achieved at the
      expense of unacceptable toxicity. One avenue to improve the therapeutic index of
      cytokines in cancer therapy consists of fusing them to monoclonal antibodies
      capable of a selective localization at the tumor site. We have constructed fusion
      proteins of interleukin-12 (IL-12) and tumor necrosis factor (TNF-alpha) with
      L19, an antibody fragment specific to the extradomain B of fibronectin which has
      been shown to target tumors in animal models and in patients with cancer. These
      fusions display a potent antitumor activity in several immunocompetent murine
      models of cancer but do not lead to complete remissions of established aggressive
      tumors. In this article, we have evaluated the tumor-targeting properties and the
      anticancer activities of combinations of the two antibody-cytokine fusion
      proteins, as well as of a triple fusion protein between IL-12, L19, and TNF
      alpha. Although all fusion proteins were active in vitro, the triple fusion
      protein failed to localize to tumors in vivo and to show significant therapeutic
      effects. By contrast, the combination of IL-12-L19 and L19-TNF-alpha displayed
      potent synergistic anticancer activity and led to the eradication of F9
      teratocarcinomas grafted in immunocompetent mice. When cured mice were
      rechallenged with tumor cells, a delayed onset of tumor growth was observed,
      indicating the induction of a partial antitumor vaccination effect. Potent
      anticancer effects were achieved at doses of IL-12-L19 and L19-TNF-alpha (2 micro
      g + 2 micro g/mouse), which were at least 5-fold lower than the maximal-tolerated
      dose. The combined administration of the two fusion proteins showed only a modest
      increase in toxicity, compared with treatments performed with the individual
      fusion proteins. These results show that the targeted delivery of cytokines to
      the tumor environment strongly potentiates their antitumor activity and that the
      combination treatment with IL-12-L19 and L19-TNF-alpha appears to be synergistic
      in vivo.

PMID- 12810650
TI  - Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing
      activity.
AB  - During the course of a mechanism-based screening program designed to identify new
      microtubule-disrupting agents from natural products, we identified a crude
      extract from Tacca chantrieri that initiated Taxol-like microtubule bundling.
      Bioassay-directed purification of the extract yielded the highly oxygenated
      steroids taccalonolides E and A. The taccalonolides caused an increased density
      of cellular microtubules in interphase cells and the formation of thick bundles
      of microtubules similar to the effects of Taxol. Mitotic cells exhibited abnormal
      mitotic spindles containing three or more spindle poles. The taccalonolides were
      evaluated for antiproliferative effects in drug-sensitive and multidrug-resistant
      cell lines. The data indicate that taccalonolide E is slightly more potent than
      taccalonolide A in drug-sensitive cell lines and that both taccalonolides are
      effective inhibitors of cell proliferation. Both taccalonolides are poorer
      substrates for transport by P-glycoprotein than Taxol. The ability of the
      taccalonolides to circumvent mutations in the Taxol-binding region of beta
      tubulin was examined using the PTX 10, PTX 22, and 1A9/A8 cell lines. The data
      suggest little cross-resistance of taccalonolide A as compared with Taxol,
      however, the data from the PTX 22 cell line indicate a 12-fold resistance to
      taccalonolide E, suggesting a potential overlap of binding sites. Characteristic
      of agents that disrupt microtubules, the taccalonolides caused G(2)-M
      accumulation, Bcl-2 phosphorylation, and initiation of apoptosis. The
      taccalonolides represent a novel class of plant-derived microtubule-stabilizers
      that differ structurally and biologically from other classes of microtubule
      stabilizers.

PMID- 12810651
TI  - Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks
      that stimulate RAD51-mediated repair pathways.
AB  - Combination of cis-platinum with ionizing radiation is one of the most promising
      anticancer treatments that appears to be more efficient than radiotherapy alone.
      Unlike conventional X-ray emitters, accelerators of high energy particles like
      synchrotrons display powerful and monochromatizable radiation that makes the
      induction of an Auger electron cascade in cis-platinum molecules [also called
      photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we
      examined the molecular consequences of one of the first attempts of synchrotron
      PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble
      France). PAT-Plat was found to result in an extra number of slowly repairable DNA
      double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear
      relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and
      activation of proto-oncogenic c-Abl tyrosine kinase.

PMID- 12810652
TI  - Differential effects of the breast cancer resistance protein on the cellular
      accumulation and cytotoxicity of 9-aminocamptothecin and 9-nitrocamptothecin.
AB  - Breast cancer resistance protein (BCRP)/MXR/ABCG2 is a new member of the family
      of ATP-dependent drug efflux proteins. Whereas overexpression of another member
      of this family, P-glycoprotein, minimally affects the cytotoxicity of
      camptothecins (CPTs), overexpression of wild-type as well as certain mutant BCRPs
      confers resistance to CPT analogues that are used clinically, including topotecan
      and irinotecan. Relatively little is known regarding the effects of BCRP on other
      CPT analogues. We now report studies of 9-aminocamptothecin (9-AC) and 9
      nitrocamptothecin (9-NC) using mammalian cells stably transfected with constructs
      expressing a variety of efflux proteins, including wild-type BCRP and a mutant
      BCRP that contains a threonine rather than an arginine at position 482 (R482T).
      The results indicate that overexpression of either P-glycoprotein, multidrug
      resistance protein type 1, or multidrug resistance protein type 2 has little
      effect on the cytotoxicity of 9-NC or 9-AC. By contrast, overexpression of either
      wild-type or R482T BCRP confers resistance to 9-AC, but not to 9-NC. Furthermore,
      overexpression of wild-type or mutant BCRP is associated with reduced
      intracellular accumulation of 9-AC, but not 9-NC. In addition, immunoblotting
      studies indicate that whereas increased BCRP expression is evident in cells
      selected for resistance to irinotecan, BCRP expression is not detectable in two
      different cell lines selected for resistance to 9-NC. Taken together, these
      findings suggest that wild-type as well as R482T BCRP mediates cellular efflux of
      9-AC but not 9-NC. Furthermore, the results suggest that polar groups at the 9 or
      10 position of the CPT A ring facilitate interaction with BCRP and have
      implications for the clinical development of new CPT analogues.

PMID- 12810653
TI  - Interleukin-6 fused to an anti-idiotype antibody in a vaccine increases the
      specific humoral immune response against CA125+ (MUC-16) ovarian cancer.
AB  - Anti-idiotypic (Id) monoclonal antibodies can serve as surrogate for tumor
      associated antigens in vaccination strategies. The murine anti-Id monoclonal
      antibody ACA125 that mimics the CA125 carbohydrate antigen expressed on ovarian
      cancer cells induces an anti-anti-Id antibody (Ab3) response that is associated
      with prolonged survival of ovarian cancer patients. To increase the Ab3 antibody
      response, we evaluated two strategies in a mouse model: (a) coinjection of human
      interleukin (IL)-6 together with the fusion protein chACA125, which consists of
      the anti-Id ACA125 single-chain Fv antibody joined to the human IgG1 CH2/CH3
      domain; and (b) injection of the fusion protein chACA125-IL-6, which consists of
      the ACA125 single-chain Fv fused to human IL-6 via the IgG1 CH2/CH3 domain.
      Vaccination of mice with the chACA125-IL-6 fusion protein resulted in higher
      titers of anti-CA125 (Ab3) antibodies compared with application of the chACA125
      antibody with or without systemic coadministration of IL-6. Application of the
      chACA125-IL-6 fusion protein did not elicit detectable antihuman IL-6 antibody
      titers, whereas coinjection of human IL-6 did. Taken together, these data suggest
      that the chACA125-IL-6 fusion protein directly stimulates ACA125-specific B cells
      via the IL-6 domain, whereas coinjection of IL-6 leads to an overall immune
      stimulation. Antigen-IL-6 fusion proteins will improve vaccination regimens and
      anticancer immunotherapeutic strategies by increasing the antigen-specific
      humoral immune response.

PMID- 12810654
TI  - Geldanamycin and its 17-allylamino-17-demethoxy analogue antagonize the action of
      Cisplatin in human colon adenocarcinoma cells: differential caspase activation as
      a basis for interaction.
AB  - Several chaperone-binding drugs based on geldanamycin (GA) have been synthesized,
      and one of them, 17-allylamino-17-demethoxygeldanamycin (17-AAG), is being
      developed in the clinic. Interest in the use of 17-AAG in combination with
      cytotoxic drugs led us to study both GA and 17-AAG with cisplatin (DDP) in the
      human colon adenocarcinoma cell lines HT29 and HCT116. We performed isobologram
      analysis of combinations of DDP with GA or 17-AAG in these cell lines using the
      standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to
      evaluate cell survival. In HCT116, the effects of GA and 17-AAG with DDP were
      additive and schedule dependent. In HT29 both GA and 17-AAG antagonized DDP
      effects resulting in cytotoxicity less than expected. We hypothesized that the
      antagonism in HT29 cells might be a consequence of altered p53 function in this
      cell line. Accordingly, we tested GA/17-AAG and DDP in combination in the HCTp5.2
      cell line, which expresses a dominant-negative form of p53. In these cells too,
      the GA analogues antagonized DDP, suggesting a role for p53 in the observed
      effects. Investigation of the DDP-induced signaling pathways revealed that
      ansamycins block the activation of mitogen-activated protein kinase and c-Jun
      NH(2)-terminal kinase pathways and c-Jun expression in HT29 cells while exerting
      incomplete inhibitory effects in HCT116 and HCTp5.2 cell lines. Therefore,
      effects on signaling are thought not to underlay the antagonism in the latter
      model. The ansamycins inhibited DDP-induced activation of caspases 8 and 3 in
      HT29 and HCTp5.2 but not in HCT116 cells, which we postulate to be the basis for
      higher survival of p53-deficient cells when treated with combinations of the two
      drugs.

PMID- 12810655
TI  - The different biological effects of telomestatin and TMPyP4 can be attributed to
      their selectivity for interaction with intramolecular or intermolecular G
      quadruplex structures.
AB  - Demonstration of the existence of G-quadruplex structures in telomeres of
      Stylonychia macronuclei and in the promoter of c-myc in human cells has validated
      these secondary DNA structures as potential targets for drug design. The next
      important issue is the selectivity of G-quadruplex-interactive agents for the
      different types of G-quadruplex structures. In this study, we have taken an
      important step in associating specific biological effects of these drugs with
      selective interaction with either intermolecular or intramolecular G-quadruplex
      structures formed in telomeres. Telomestatin is a natural product isolated from
      Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase
      inhibitor through its G-quadruplex interaction. We have demonstrated that
      telomestatin interacts preferentially with intramolecular versus intermolecular G
      quadruplex structures and also has a 70-fold selectivity for intramolecular G
      quadruplex structures over duplex DNA. Telomestatin is able to stabilize G
      quadruplex structures that are formed from duplex human telomeric DNA as well as
      from single-stranded DNA. Importantly, telomestatin stabilizes these G-quadruplex
      structures in the absence of monovalent cations, which is a unique characteristic
      among G-quadruplex-interactive compounds. At noncytotoxic concentrations,
      telomestatin suppresses the proliferation of telomerase-positive cells within
      several weeks. In contrast, TMPyP4, a compound that preferentially facilitates
      the formation of intermolecular G-quadruplex structures, suppresses the
      proliferation of alternative lengthening of telomeres (ALT)-positive cells as
      well as telomerase-positive cells. We have also demonstrated that TMPyP4 induces
      anaphase bridges in sea urchin embryos, whereas telomestatin did not have this
      effect, leading us to conclude that the selectivity of telomestatin for
      intramolecular G-quadruplex structures and TMPyP4 for intermolecular G-quadruplex
      structures is important in mediating different biological effects: stabilization
      of intramolecular G-quadruplex structures produces telomerase inhibition and
      accelerated telomere shortening, whereas facilitation of the formation of
      intermolecular G-quadruplex structures induces the formation of anaphase bridges.

PMID- 12810656
TI  - Specific tumoricidal activity of a secreted proapoptotic protein consisting of
      HER2 antibody and constitutively active caspase-3.
AB  - In this study, a novel approach to antitumor therapy was devised by generating a
      chimeric tumor-targeted killer protein, referred to as immunocasp-3, that
      comprises a single-chain anti-erbB2/HER2 antibody with a NH(2)-terminal signal
      sequence, a Pseudomonas exotoxin A translocation domain, and a constitutively
      active caspase-3 molecule. In principle, cells transfected with the immunocasp-3
      gene would express and secrete the chimeric protein, which then binds to HER2
      overexpressing tumor cells. Subsequent cleavage of the constitutively active
      capase-3 domain from the immunocasp-3 molecule and its release from internalized
      vesicles would lead to apoptotic tumor cell death. To test this strategy, we
      transduced human lymphoma Jurkat cells with a chimeric immunocasp-3 gene
      expression vector and showed that they not only expressed and secreted the fusion
      protein but also selectively killed tumor cells overexpressing HER2 in vitro.
      i.v. injection of the transduced Jurkat cells led to tumor regression in a mouse
      xenograft model because of continuous secretion of immunocasp-3 by the transduced
      cells. The growth of HER2-positive tumor cells in this model was inhibited by
      i.m. as well as intratumor injection of immunocasp-3 expression plasmid DNA,
      indicating that the immunocasp-3 molecules secreted by transfected cells have
      systematic antitumor activity. We conclude that the immunocasp-3 molecule,
      combining the properties of a tumor-specific antibody with the proapoptotic
      activity of a caspase, has potent and selective antitumor activity, either as
      cell-based therapy or as a DNA vaccine. These findings provide a compelling
      rationale for therapeutic protocols designed for erbB2/HER2-positive tumors.

PMID- 12810657
TI  - Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of
      ovarian carcinoma cells.
AB  - Flavopiridol, a cyclin-dependent kinase (cdk) inhibitor, can cause cell cycle
      arrest, induce apoptosis in cancer cells, and inhibit tumor cell growth in vivo.
      The present study investigated the in vitro radiosensitizing effect of
      flavopiridol and the underlying molecular mechanisms in a murine ovarian cancer
      cell line, OCA-I. Flavopiridol inhibited cell growth in a dose-dependent manner
      and enhanced cell radiosensitivity assessed by the clonogenic cell survival
      assay. A flavopiridol dose of 300 nM, given for 1 day, enhanced radiosensitivity
      by a factor of 2.1. Clonogenic cell survival after split-dose radiation showed
      that flavopiridol inhibited repair from radiation damage. In addition,
      flavopiridol treatment (300 nM, 1 day) resulted in decreased levels of Ku70 and
      Ku86 proteins that play a role in DNA repair processes, suggesting that DNA
      repair processes may have been disrupted by this agent. Flow cytometry analysis
      showed that flavopiridol (300 nM, 1 day) accumulated the cells in G(1) and G(2)
      phases, with a significant reduction in the S phase component. This cell cycle
      redistribution is likely another mechanism underlying flavopiridol-induced cell
      radiosensitivity. Flavopiridol down-regulated cyclin D1 and cyclin E protein
      levels and also inhibited phosphorylation of retinoblastoma protein, which is
      inconsistent with the observed cell cycle arrest. Among the cdks tested, cdk-9,
      the catalytic subunit of positive transcription elongation factor b, was
      significantly down-regulated by flavopiridol, suggesting that flavopiridol may
      modulate cellular transcription processes. Furthermore, flavopiridol on its own
      induced apoptosis in the OCA-I cells, whereas in combination with radiation,
      exerted no additional increase in apoptosis. Taken together, our data show that
      flavopiridol strongly augmented the response of ovarian carcinoma cells to
      radiation and that the underlying mechanisms included inhibition of sublethal DNA
      damage repair and cell cycle redistribution. At the molecular level,
      transcriptional regulation by flavopiridol may have been involved.

PMID- 12810659
TI  - Antigen-driven clonal proliferation, somatic hypermutation, and selection of B
      lymphocytes infiltrating human ductal breast carcinomas.
AB  - Infiltration of B lymphocytes into the tumor tissue of breast cancer patients is
      a common occurrence, but the role of these cells in the immune response to the
      tumor is unknown. Heavy B-cell infiltration in medullary breast carcinoma is well
      documented and associated with a more favorable prognosis, implying a positive
      role for the humoral immune response in elimination of tumor cells. Variable B
      cell infiltration has also been detected in infiltrating ductal carcinomas of the
      breast, but little is known about the immunoglobulin gene repertoire of these
      tumor-infiltrating B lymphocytes and whether they are actively responding to a
      local stimulus or merely passive bystanders. We have therefore investigated the
      repertoire of B cells infiltrating four invasive ductal carcinomas. A group of
      233 rearranged Ig V(H) genes was amplified, cloned, and sequenced from
      microdissected foci of infiltrating B cells. B cells within individual foci were
      polyclonal, and most were highly mutated. Several foci expressed dominant sets of
      V genes derived from B-cell clones. Some of these were found in more than one
      lymphoid cluster, indicating that B cells had migrated into the surrounding
      tissue and seeded new clusters. Analysis of the pattern of mutations in clonally
      related sets of Ig V genes expressed by tumor-infiltrating B cells shows that
      these cells are undergoing antigen-driven proliferation, somatic hypermutation,
      and affinity maturation in situ.

PMID- 12810658
TI  - Adenovirus-mediated heat-activated antisense Ku70 expression radiosensitizes
      tumor cells in vitro and in vivo.
AB  - Ku70 is one component of a protein complex, Ku70 and Ku80, that functions as a
      heterodimer to bind DNA double-strand breaks and activates DNA-dependent protein
      kinase. Our previous study with Ku70-/- and Ku80-/- mice, and cell lines has
      shown that Ku70- and Ku80-deficiency compromises the ability of cells to repair
      DNA double-strand breaks, increases radiosensitivity of cells, and enhances
      radiation-induced apoptosis. In this study, we examined the feasibility of using
      adenovirus-mediated, heat-activated expression of antisense Ku70 RNA as a gene
      therapy paradigm to sensitize cells and tumors to ionizing radiation. First, we
      performed experiments to test the heat inducibility of heat shock protein (hsp)
      70 promoter and the efficiency of adenovirus-mediated gene transfer in rodent and
      human cells. Replication-defective adenovirus vectors were used to introduce a
      recombinant DNA construct, containing the enhanced green fluorescent protein
      (EGFP) under the control of an inducible hsp70 promoter, into exponentially
      growing cells. At 24 h after infection, cells were exposed to heat treatment, and
      heat-induced EGFP expression at different times was determined by flow cytometry.
      Our data clearly show that heat shock at 42 degrees C, 43 degrees C, or 44
      degrees C appears to be equally effective in activating the hsp70 promoter-driven
      EGFP expression (>300-fold) in various tumor cells. Second, we have generated
      adenovirus vectors containing antisense Ku70 under the control of an inducible
      hsp70 promoter. Exponentially growing cells were infected with the adenovirus
      vector, heat shocked 24 h later, and the radiosensitivity determined 12 h after
      heat shock. Our data show that heat shock induces antisense Ku70 RNA, reduces the
      endogenous Ku70 level, and significantly increases the radiosensitivity of the
      cells. Third, we have performed studies to test whether Ku70 protein level can be
      down-regulated in a solid mouse tumor (FSa-II), and whether this results in
      enhanced radiosensitivity in vivo, as assessed by in vivo/in vitro colony
      formation and by the tumor growth delay. Our data demonstrate that heat-shock
      induced expression of antisense Ku70 RNA attenuates Ku70 protein expression in
      FSa-II tumors, and significantly sensitizes the FSa-II tumors to ionizing
      radiation. Taken together, our results suggest that adenovirus-mediated, heat
      activated antisense Ku70 expression may provide a novel approach to
      radiosensitize human tumors.

PMID- 12810660
TI  - Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide
      vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade.
AB  - Although peptide immunization often leads to the induction of strong T-cell
      responses, it is seldom effective against established tumors. One possibility is
      that these T-cell responses are not strong enough or do not last sufficiently
      long to have an effect in tumor eradication. Here, we examined the role of
      synthetic oligodeoxynucleotide (ODN) adjuvants containing unmethylated cytosine
      guanine motifs (CpG-ODN) and CTLA-4 blockade in enhancing the antitumor
      effectiveness of peptide vaccines intended to elicit CTL responses. The results
      show that combination immunotherapy consisting of vaccination with a synthetic
      peptide corresponding to an immunodominant CTL epitope derived from tyrosinase
      related protein-2 administered with CpG-ODN adjuvant and followed by systemic
      injection of anti-CTLA-4 antibodies increased the survival of mice against the
      poorly immunogenic B16 melanoma. Interestingly, whereas this combination therapy
      was effective when administered to tumor-bearing mice (therapeutic protocol), it
      had no significant effect when applied in the prophylactic mode (i.e., before the
      tumor challenge). Moreover, the antitumor effect of the combination immunotherapy
      required the participation of CD4+ and CD8+ T lymphocytes and was accompanied by
      the induction of antitumor CD4+ T-cell responses. The overall results suggest
      that peptide vaccination of tumor-bearing mice, applied in combination with a
      strong adjuvant and CTLA-4 blockade, is capable of eliciting durable antitumor T
      cell responses that provide survival benefit. These findings bear clinical
      significance for the design of peptide-based therapeutic vaccines for human
      cancer patients.

PMID- 12810661
TI  - The G2-phase decatenation checkpoint is defective in Werner syndrome cells.
AB  - It has been proposed that cells monitor chromatid catenation status after DNA
      replication and inhibit progression into mitosis until chromatids are correctly
      decatenated by topoisomerase II (TopoII). Studies in yeast have suggested that
      TopoII may interact with RecQ helicases during this process. Using ICRF187, a
      TopoII catalytic inhibitor that prevents chromatid decatenation without producing
      DNA strand breaks, we demonstrated that cells deficient of WRN, a human RecQ
      helicase, displayed a defect in decatenation checkpoint activation, which was
      corrected by ectopic expression of wild-type WRN. We also provide evidence that
      BRCA1 is phosphorylated in an ATR-dependent manner in response to decatenation
      checkpoint activation and that this phosphorylation is not detectable in Werner
      syndrome cells. Furthermore, ICRF187 treatment resulted in coimmunoprecipitation
      of WRN and TopoII. Finally, we demonstrated that override of the decatenation
      checkpoint resulted in enhanced chromosomal damage and apoptosis only in the
      absence of WRN, but not in normal cells. Our findings suggest that WRN plays a
      role in the activation of G(2) decatenation checkpoint and that the abortive
      function of this pathway itself does not appear to be sufficient to cause genomic
      instability but rather predisposes to genomic instability and apoptotic cell
      death in the absence of other "caretaker" genes, such as WRN.

PMID- 12810662
TI  - Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with
      fumarate hydratase homology.
AB  - Human alpha-methylacyl-CoA racemase (AMACR) was overexpressed in prostate cancer
      compared with nonmalignant tissues. The Gene Logic Inc. BioExpress database
      containing Affymetrix U133 GeneChip expression profiles of 4400 human normal,
      benign, diseased, and tumor samples from >60 tissue types was examined to
      determine the specificity of AMACR mRNA expression. One particular AMACR probeset
      was derived from an alternatively spliced exon with 88% identity to a 521-bp
      sequence that spans four exons of the fumarate hydratase. The predicted protein
      sequence revealed a novel GLGELIL peptide shared by both proteins. Whether the
      mitochondrial and peroxisomal AMACR described previously are distinct products
      from alternatively spliced transcripts remains to be determined. The
      determination of the cellular location and function of the altered AMACR will be
      critical in the elucidation of the role of AMACR in prostate cancer diagnosis and
      pathogenesis.

PMID- 12810663
TI  - A yeast two-hybrid assay provides a simple way to evaluate the vast majority of
      hMLH1 germ-line mutations.
AB  - Germ-line mutations in the hMLH1 gene are the most frequent cause of hereditary
      nonpolyposis colorectal cancer and are characterized by missense mutations at
      high frequency. We found a yeast two-hybrid assay to be an extremely useful and
      simple tool for evaluating the biological significance of such hMLH1 germ-line
      missense mutations; 78% (18 of 23) of the missense ones can be recognized as
      causative for nonpolyposis colorectal cancer. In addition, two of five variants
      not recognized as causative were thought to be rare polymorphisms. However, we
      could not detect any differences between wild-type hMLH1 and any of the nine
      already known polymorphisms causing amino acid alterations. Additional analysis
      demonstrated that the two-hybrid assay not only detected the dysfunctions at the
      COOH terminus of the hMLH1 protein necessary for the interaction with associated
      proteins but also detected a conformational change at the NH(2) terminus carrying
      ATPase activity. Thus, this method provides a simple and reliable system for
      accurate diagnosis of hMLH1 alterations.

PMID- 12810664
TI  - A combined comparative genomic hybridization and expression microarray analysis
      of gastric cancer reveals novel molecular subtypes.
AB  - Comparative genomic hybridization (CGH), microsatellite instability (MSI) assays,
      and expression microarrays were used to molecularly subclassify a common set of
      gastric tumor samples. We identified a number of novel genomic aberrations
      associated with gastric cancer and discovered that gastric tumors could be
      grouped by their expression profiles into three broad classes: "tumorigenic,"
      "reactive," and "gastric-like." Patients with gastric-like tumors exhibited a
      significantly better overall survival than patients belonging to the other two
      classes (P < 0.05). A novel supervised learning methodology for multiclass
      prediction was used to identify optimal predictor gene sets that accurately
      predicted the class of an unknown tumor sample. These predictor sets may prove
      useful in the development of new diagnostic applications for gastric cancer
      staging and prognostication.

PMID- 12810665
TI  - Fine mapping and identification of candidate pulmonary adenoma susceptibility 1
      genes using advanced intercross lines.
AB  - In the present study, we used newly developed F(11) generation mouse advanced
      intercross lines (AIL) to fine map Pas1-3 quantitative trait loci (QTL). The (A/J
      x C57BL/6) F(11) AIL mouse population was created by crossing lung tumor
      resistant C57BL/6 mice with lung tumor-susceptible A/J mice. By selectively
      genotyping 30% of the population, we have confirmed the Pas1 QTL and narrowed it
      to an interval of approximately 1.0 cM or 1.3 Mb in the vicinity of the Kras2
      gene. The Pas2 QTL was detected by both ANOVA and regression analysis but not by
      MapMaker EXP/QTL software. In addition, an interaction between the Pas1 and Pas2
      QTLs was revealed. However, the Pas3 QTL was not confirmed in this study. It was
      either lost during the development of the AIL or too weak to be detected using
      AIL. The Pas1 locus is now sufficiently fine-mapped that candidate gene(s) for
      the Pas1 locus can be characterized by positional cloning. In this study, all 27
      of the known or predicted genes located in the Pas1 candidate region were
      characterized as possible candidate Pas genes. Six genes were selected for
      additional analyses because of their relevant function in tumorigenesis or
      allelic changes between A/J and C57BL/6 mice. The Lrmp gene bears amino acid
      polymorphisms among various mouse strains that are highly correlated with the
      Pas1 allele status. The Pas1c1 gene (RIKEN Ak016641), encoding an intermediate
      filament tail domain-containing protein, produces alternatively spliced
      transcripts across inbred strains of mice, and its splicing pattern cosegregates
      with the Pas1 allele. The genetic and expression data support these two genes as
      strong candidates for the Pas1 locus. Of the other four genes (Eca39, RIKEN
      Ak015530, mHoj-1, and Krag), no functional polymorphisms or differential gene
      expression were found in Eca39, mHoj-1, and Krag between lung tumor-susceptible
      and -resistant strains. The Ak015530 carries an amino acid polymorphism, but this
      polymorphism does not cosegregate with mouse lung tumor susceptibility. Thus,
      these 4 genes are less likely candidates for the Pas1 locus.

PMID- 12810666
TI  - Contributions of ATM mutations to familial breast and ovarian cancer.
AB  - This study addresses the prevalence of ATM mutations and the association with
      breast cancer in Austrian families selected for a history of breast or ovarian
      cancer or both [hereditary breast and ovarian cancer (HBOC)]. In 270 HBOC
      families previously screened for BRCA1 and BRCA2 mutations, 137 different
      sequence alterations of ATM were identified. Seven of these were mutations
      presumed to cause ataxia telangiectasia based on their effect on the ATM protein,
      including five that caused a protein truncation and two missense mutations in the
      catalytic kinase domain of the highly conserved COOH terminus of the protein. The
      seven mutations were found in 10 families (3.7%). In addition, one missense
      variant, L1420F, was observed in 13 HBOC families (4.8%) but was not observed in
      any of the 122 healthy volunteers with no history of breast cancer. In addition,
      the variant segregated with breast cancer in some of the families, suggesting
      that it may be pathogenic for breast cancer. Sixty-two additional variants of
      potential significance were observed in 65 HBOC families, but not in healthy
      controls. These variants included 24 sequence alterations with possible effects
      on splicing or protein-protein interactions. This study indicates that there is a
      significant prevalence of ATM mutations in breast and ovarian cancer families and
      adds to a growing body of evidence that ATM mutations confer increased
      susceptibility to breast cancer.

PMID- 12810667
TI  - MSH2-deficient human cells exhibit a defect in the accurate termination of
      homology-directed repair of DNA double-strand breaks.
AB  - Mutations in the mismatch repair (MMR) genes hMSH2 and hMLH1 have been associated
      with hereditary nonpolyposis colorectal cancer. Tumor cell lines that are
      deficient in MMR exhibit a high mutation rate, a defect in the response to
      certain types of DNA damage and in transcription-coupled repair, as well as an
      increase in the rate of gene amplification. We show here that hMSH2-deficient
      tumor cell lines lost most of their ability to accurately repair plasmid DNA
      double-strand breaks (DSBs) by homologous recombination, compared with MMR
      proficient or hMLH1-deficient tumor cell lines. In all of these cell lines, DSB
      repair occurred almost exclusively by nonreciprocal homologous recombination:
      gene conversion (GC). However, there were two types of GC products: precise and
      rearranged. The rearranged products contained deletions or insertions of
      sequences and represented GC intermediates trapped at various stages and shunted
      to nonhomologous end joining. In MMR-proficient or MLH1-deficient cells, >50% of
      GC products were of the precise type, whereas in two MSH2-deficient backgrounds,
      this proportion decreased to 8%, whereas that of rearranged GC products increased
      by 2-fold. These results seem to predict a novel way by which MSH2-deficiency
      could promote mutation: deletion or insertion mutations associated with DSB
      repair, which may also contribute to cancer predisposition.

PMID- 12810668
TI  - Transforming growth factor beta 1 increases the stability of p21/WAF1/CIP1
      protein and inhibits CDK2 kinase activity in human colon carcinoma FET cells.
AB  - We examined transforming growth factor-beta 1 (TGF-beta 1) effects on cell cycle
      progression of human colon carcinoma FET cells. TGF-beta 1 inhibited DNA
      synthesis and cyclin-dependent kinase (CDK) activity after release from growth
      arrest in association with induction of the p21 CDK inhibitor, whereas cyclins,
      CDKs, and p27 protein levels remained relatively unchanged. The decrease in CDK2
      kinase activity was the result of increased p21 association with cyclin A-CDK2
      and cyclin E-CDK2. TGF-beta 1 treatment in late G(1) showed reduced induction of
      p21 protein levels in association with increased DNA synthesis. Consequently, p21
      induction in early G(1) is critical for TGF-beta 1 inhibition of CDK2 kinase
      activity. Although TGF-beta 1 treatments in late G(1) failed to induce p21
      protein, p21 mRNA induction was observed in late G(1) and in S phase. Further
      analysis showed that TGF-beta 1 treatment in early G(1) increases p21 protein
      stability throughout the G(1) and S phases of the cell cycle. Our results
      demonstrate that TGF-beta 1 stimulation of p21 is regulated at the
      posttranscriptional and transcriptional levels. This is a novel mechanism of TGF
      beta 1 inhibition requiring early G(1) induction and stabilization of p21
      protein, which binds to and inhibits cyclin E-CDK2 and cyclin A-CDK2 kinase
      activity rather than direct modulation of cyclin or CDK protein levels as seen in
      other systems.

PMID- 12810669
TI  - Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and
      allelic differences in the response to selenium.
AB  - A role for allelic variation within the gene for the antioxidant selenoprotein
      glutathione peroxidase 1 (GPx-1) in the risk or etiology of breast cancer was
      investigated. By analyzing the frequency of a polymorphism within the GPx-1 gene
      resulting in a leucine or proline at codon 198, it was determined that the
      leucine-containing allele was more frequently associated with breast cancer than
      the proline-containing allele (odds ratio = 1.9; P < 0.05). However, the
      heterozygosity index for this polymorphism was lower in the breast cancer
      samples. To determine whether this was because of the loss of heterozygosity
      (LOH) during tumor development, another polymorphic marker within GPx-1, which is
      frequently heterozygous in the human population, was analyzed. These studies
      indicated that LOH at this locus is a frequent event, occurring in approximately
      36% of the breast tumor DNAs analyzed. The consequences of the identity of the
      amino acid at position 198 were investigated by engineering breast carcinoma
      cells that exclusively express either the leucine- or proline-containing GPx-1
      allele and studying the response to increasing concentrations of selenium. These
      studies indicated that the leucine-containing allele was less responsive to the
      stimulation of GPx-1 enzyme activity observed during selenium supplementation
      than the allele differing only by a proline at that position. These studies
      support a role for GPx-1 allelic identity and LOH as factors of significance to
      breast cancer development.

PMID- 12810670
TI  - Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B
      in non-small cell lung cancer.
AB  - The aim of this study was to evaluate the promoter methylation status and loss of
      heterozygosity (LOH) of the SEMA3B in non-small cell lung cancers (NSCLCs). We
      analyzed the methylation status of semaphorin 3B (SEMA3B) promoter and LOH at
      3p21.3 in eight NSCLC cell lines and 27 primary tumors. Hypermethylation of
      SEMA3B was found in 50% of the cell lines and 41% of the primary tumors studied.
      The presence of hypermethylation was statistically associated with loss of SEMA3B
      expression in both cell lines (P = 0.02) and primary tumors (P < 0.01). There was
      no correlation between SEMA3B and tumor stage. On the other hand, the correlation
      between SEMA3B methylation status and LOH at 3p21.3 was significant (P = 0.02).
      Notably, 7 of 8 tumors with both hypermethylation and LOH of SEMA3B showed the
      absence of the expression. Treatment with 5-AZAC restored SEMA3B expression in
      NSCLC cell line. These results indicate that SEMA3B gene alterations may play a
      important role in the malignant transformation of NSCLC via a two-hit mechanism,
      including epigenetic changes and allelic loss, for tumor suppressor gene
      inactivation.

PMID- 12810671
TI  - The Ste20 kinase MST4 plays a role in prostate cancer progression.
AB  - MST4, a member of the Sterile 20 serine/threonine kinase family, was found to be
      expressed in prostate carcinoma tumor samples and cell lines. In addition,
      expression levels appeared to correlate with tumorigenicity and androgen receptor
      status of the cells. Ectopic expression of wild-type and kinase-inactive MST4 was
      used to alter cellular MST4 activity levels in three widely studied human
      prostate tumor cell lines: LNCaP, DU 145, and PC-3. Overexpression of wild-type
      MST4 induced anchorage-independent growth of the LNCaP cell line, and increased
      both in vitro proliferation and in vivo tumorigenesis of the DU 145 cell line. On
      the other hand, expression of a kinase-inactive form reverted the anchorage
      independent growth phenotype and highly tumorigenic behavior of the PC-3 cell
      line. MST4 kinase activity was stimulated significantly by epidermal growth
      factor receptor ligands, which are known to promote growth of prostate cancer
      cells. Together, our studies suggest a potential role for MST4 in the signal
      transduction pathways involved in prostate cancer progression.

PMID- 12810672
TI  - Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by
      other testican family proteins.
AB  - Testican family proteins are putative extracellular heparan/chondroitin sulfate
      proteoglycans of unknown function. We identified recently N-Tes, which is a
      product of testican 3 splicing variant gene, as an inhibitor of membrane-type
      matrix metalloproteinases (MT-MMPs). The inhibitory function is common among
      testican family members except for testican 2, which was shown to uniquely
      abolish inhibition of MT1-MMP- or MT3-MMP-mediated pro-MMP-2 activation by other
      testican family members. Testican 2 inactivates N-Tes by binding to the COOH
      terminal extracellular calcium-binding domain of N-Tes through its NH(2)-terminal
      unique domain as demonstrated by coimmunoprecipitation analysis, and, thus,
      testican 2 was unable to inactivate a N-Tes deletion mutant lacking the
      extracellular calcium-binding domain (N-Tes-Delta 122). Migration of U251 cells
      on collagen, which was dependent on MT1-MMP activity under serum-free condition,
      was inhibited by N-Tes or N-Tes-Delta 122 deposited on collagen. Testican 2 was
      not incorporated into collagen by itself, and was deposited only in the presence
      of N-Tes, suggesting that testican 2 binds to N-Tes deposited on collagen.
      Binding of testican 2 to N-Tes deposited on collagen allowed migration of cells
      expressing MT1-MMP. Unlike wild-type N-Tes, N-Tes-Delta 122 did not bind to
      testican 2, and, thus, expression of testican 2 did not recover cell migration
      blocked by N-Tes-Delta 122. In situ hybridization showed that neurons are a major
      source of all of the testican family members in the normal brain. The
      quantitative reverse transcription-PCR analysis demonstrated that all of the
      testican family members are expressed prominently in normal brain, and their
      expression levels decrease as tumor grade increases. The expression level of
      testican 2 was the highest among testican family members regardless of
      histological grade of astrocytic tumors. These results suggest that abundant
      distribution of testican 2 may contribute to glioma invasion by inactivating
      other testican family members including N-Tes, which all inhibit MT-MMPs. We
      propose that N-Tes-Delta 122, which is resistant to testican 2, may have
      therapeutic potential as a barrier against glioma invasion.

PMID- 12810673
TI  - Angiopoietin-1 inhibits vascular permeability, angiogenesis, and growth of
      hepatic colon cancer tumors.
AB  - Angiopoietin (Ang)-1 and -2 are critical regulators of embryonic and postnatal
      neovascularization. Ang-1 activates the endothelial cell-specific tyrosine kinase
      receptor Tie-2, which in turn leads to enhanced endothelial cell survival and
      stabilization. The effects of Ang-1 on tumor angiogenesis remain controversial;
      although we have previously demonstrated that Ang-1 overexpression in colon
      cancer cells leads to a decrease in s.c. tumor growth, others have shown that Ang
      1 may be proangiogenic. Few studies have addressed the role of the Angs in tumors
      growing in the organ of metastatic growth. We hypothesized that overexpression of
      Ang-1 may inhibit the growth of colon cancers growing in the liver by inhibition
      of angiogenesis. We also wanted to investigate the mechanisms by which Ang-1
      affects angiogenesis in vivo. Human colon cancer cells (HT29) were stably
      transfected with an Ang-1 construct or an empty vector (pcDNA) and injected
      directly into the livers of nude mice. After 37 days, livers were harvested and
      weighed, and tumor sizes were measured. In an additional experiment, to validate
      the paracrine effect of Ang-1, various mixtures of control cells and Ang-1
      transfected cells were injected into livers, and tumor growth was assessed.
      Direct effects of recombinant Ang-1 on angiogenesis were studied with an in vivo
      Gelfoam angiogenesis assay. The impact of Ang-1 on vascular permeability was
      investigated using an intradermal Miles assay with conditioned media from
      transfected cells. Liver weights (P < 0.05), tumor volumes (P < 0.05), vessel
      counts (P < 0.01), and tumor cell proliferation (P < 0.01) in the Ang-1 group
      were significantly lower than those in the control (pcDNA) group. Tumor vessels
      in the Ang-1 group developed a significantly higher degree of pericyte coverage
      (P < 0.02) than vessels in pcDNA tumors. In the cell mixture experiment, even as
      few as a 1:10 mixture of Ang-1-transfected cells/control cells resulted in a
      significant reduction of hepatic tumor volumes (P < 0.04). In the angiogenesis
      assay, vessel counts in Gelfoam implants were significantly decreased by the
      addition of Ang-1 (P < 0.01). Finally, conditioned medium from Ang-1-transfected
      cells decreased vascular permeability more than that from control cells (P <
      0.05). Our results suggest that Ang-1 is an important regulator of angiogenesis
      and vascular permeability and that this effect may be secondary to increasing
      periendothelial support and vessel stabilization. Thus, Ang-1 could potentially
      serve as an antineoplastic or anti-permeability agent for patients with
      metastatic colorectal cancer.

PMID- 12810674
TI  - Ovarian carcinoma develops through multiple modes of chromosomal evolution.
AB  - Ovarian carcinoma has the highest mortality of all of the gynecologic cancers.
      The chromosomal changes in this tumor type are highly complex, and the karyotypes
      typically show severe aneuploidy. Despite the abundance of cytogenetic
      information, with approximately 400 published karyotypes, very little is known
      about the mode of karyotypic evolution and the possible presence of cytogenetic
      pathways related to tumor development. In the present investigation we used 387
      ovarian carcinoma karyotypes to identify the most frequent genomic imbalances.
      Tumor cases were then classified with respect to the presence or absence of these
      imbalances and statistically analyzed to assess the order of appearance of
      chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic
      subtypes. We establish the temporal order by which the different imbalances occur
      and show that at least two cytogenetic pathways exist, one characterized by +7,
      +8q, and +12, and one by 6q- and 1q-. We show that ovarian carcinomas develop
      through at least three phases of karyotypic evolution. At the early stages, Phase
      I, the karyotypic evolution seems to proceed though step-wise acquisition of
      changes. The transition to Phase II showed signs of an increased chromosomal
      instability, most probably caused by extensive telomere crisis and the onset of
      breakage-fusion-bridge cycles. This process was linked to the presence of
      imbalances characteristic for the 6q-/1q- pathway. The transition to Phase III
      involved triploidization and was also linked to the presence of the 6q-/1q-
      pathway.

PMID- 12810675
TI  - The gatekeeper effect of epithelial-mesenchymal transition regulates the
      frequency of breast cancer metastasis.
AB  - When carcinoma cells metastasize, they change their phenotype to enhance
      motility. Cells making this switch selectively express S100A4, a p53-associated,
      calcium-binding protein known in the fibroblast literature as fibroblast-specific
      protein-1 (FSP1). FSP1 normally acts as a conversion signal for the local
      formation of tissue fibroblasts by epithelial-mesenchymal transition. We describe
      here a novel connection between the process of fibroblast development and the
      acquisition of a metastatic phenotype in genetically engineered mice with mammary
      carcinoma. More frequent lung metastases were observed in naive recipients given
      purified populations of green fluorescent protein (GFP)(+) tumor cells harvested
      from PyV-mT x FSP1(+/+.GFP) F1 mice compared with GFP(-) tumor cells (P < or =
      0.01), where GFP expression is under the control of the FSP1 promoter. The
      expression of GFP in these metastases reversibly attenuates with the
      establishment of secondary tumor nodules. Reduced numbers of metastases were also
      observed in PyV-mT x FSP1(GFP/GFP) F1 mice carrying null alleles for FSP1 (P < or
      = 0.04) and in PyV-mT x FSP1.Delta TK(+) F1 mice rescued with nucleoside
      analogues while expressing thymidine kinase under the control of the FSP1
      promoter (P < or = 0.01). We propose that epithelial-mesenchymal transition
      associated with the expression of FSP1 in tumor cells has a functional role in
      determining the latency of tumor dispersion and may be a convenient therapeutic
      target for controlling a key initiating event in metastatic progression.

PMID- 12810676
TI  - The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis.
AB  - Most human tumors display inactivation of the p53 and the p16(INK4)/pRb pathway.
      The Ink4a/alternative reading frame (ARF) locus encodes the p16(INK4a) and
      p14(ARF) (murine p19(ARF)) proteins. p16(INK4a) is deleted in 40-60% of breast
      cancer cell lines, and p16(INK4a) inactivation by DNA methylation occurs in < or
      =30% of human breast cancers. In mice genetically heterozygous for p16(INK4a) or
      Ink4a/Arf, predisposition to specific tumor types is enhanced. Ink4a/Arf(+/-)
      mice have increased E micro -Myc-induced lymphomagenesis and epidermal growth
      factor receptor-induced gliomagenesis. ErbB2 (epidermal growth factor receptor
      related protein B2) is frequently overexpressed in human breast cancer and is
      sufficient for mammary tumorigenesis in vivo. We determined the role of
      heterozygosity at the Ink4a/Arf locus in ErbB2-induced mammary tumorigenesis.
      Compared with mouse mammary tumor virus-ErbB2 Ink4a/Arf(+/-) mice, mouse mammary
      tumor virus-ErbB2 Ink4a/Arf(wt) mammary tumors showed increased p16(INK4a),
      reduced Ki-67 expression, and reduced cyclin D1 protein but increased mammary
      tumor apoptosis with no significant change in the risk of developing mammary
      tumors. These studies demonstrate the contribution of Ink4a/Arf heterozygosity to
      tumor progression is tissue specific in vivo. In view of the important role of
      Ink4a/Arf in response to chemotherapy, these transgenic mice may provide a useful
      model for testing breast tumor therapies.

PMID- 12810677
TI  - Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in
      host endothelium and destabilizes host vasculature, supporting angiogenesis in
      ovarian cancer.
AB  - Vascular remodeling in host tissues surrounding growing tumors is implicated in
      the successful development of tumor neovasculature. Cooperation between vascular
      endothelial growth factor (VEGF) and angiopoietins (Angs) is considered to be
      critical in this context. However, the mechanisms regulating the coordinated
      expression of these molecules remain, to date, elusive. In this study, we used a
      murine ovarian cancer angiogenesis model induced by overexpression of VEGF, as
      well as 52 human ovarian cancer specimens and 36 established cancer cell lines to
      characterize the expression and regulation of Ang-2 in the context of tumor
      angiogenesis. Using a combination of immunohistochemistry, laser capture
      microdissection and real-time quantitative reverse transcription-PCR, we showed
      that tumor-derived VEGF significantly up-regulated the expression of Ang-2 in
      host stroma endothelial cells, resulting in markedly increased Ang-2/Tie-2 mRNA
      copy number ratio in vivo. In vitro experiments showed that VEGF directly up
      regulated Ang-2, which is mediated via VEGF receptor-2/flk-1/KDR pathway, in
      cultured endothelial cells through transcriptional activation rather than the
      enhanced mRNA stability. In human ovarian cancer, Ang-2 was primarily expressed
      in stroma endothelial cells and detectable in tumor cells of only 12% tumor
      specimens; however, it was not detected in the majority of established ovarian
      cancer cell lines. In addition, a significant correlation was observed between
      VEGF and Ang-2 mRNA expression (P < 0.01) but not between VEGF and Ang-1 or Tie-2
      in human ovarian cancer specimens. In the mouse ovarian cancer model, up
      regulation of Ang-2 in host stroma endothelial cells was significantly associated
      with pericyte loss and instability of the host vasculature surrounding the tumor.
      Our study suggests a novel mechanism by which tumor-derived VEGF interacts with
      Angs/Tie-2 system in host stroma endothelial cells and induces in a paracrine
      manner the remodeling of host vasculature to support angiogenesis during tumor
      growth.

PMID- 12810678
TI  - 2-Deoxy-D-glucose-induced cytotoxicity and radiosensitization in tumor cells is
      mediated via disruptions in thiol metabolism.
AB  - Exposure to ionizing radiation is believed to cause cell injury via the
      production of free radicals that are thought to induce oxidative damage. It has
      been proposed that exposure to agents that enhance oxidative stress-induced
      injury by disrupting thiol metabolism may sensitize cells to the cytotoxic
      effects of ionizing radiation. Recently, it has been shown that glucose
      deprivation selectively induces cell injury in transformed human cells via
      metabolic oxidative stress (J. Biol. Chem., 273: 5294-5299; Ann. N.Y. Acad. Sci.,
      899: 349-362), resulting in profound disruptions in thiol metabolism. Because 2
      deoxy-D-glucose (2DG) is a potent inhibitor of glucose metabolism thought to
      mimic glucose deprivation in vivo, the hypothesis that exposure to 2DG might be
      capable of inducing radiosensitization in transformed cells via perturbations in
      thiol metabolism was tested. When HeLa cells were exposed to 2DG (4-10 mM) for 4
      72 h, cell survival decreased (20-90%) in a dose- and time-dependent fashion.
      When HeLa cells were treated with 6 mM 2DG for 16 h before ionizing radiation
      exposure, radiosensitization was observed with a sensitizer enhancement ratio of
      1.4 at 10% isosurvival. Treatment with 2DG was also found to cause decreases in
      intracellular total glutathione content (50%). Simultaneous treatment with the
      thiol antioxidant N-acetylcysteine (NAC; 30 mM) protected HeLa cells against the
      cytotoxicity and radiosensitizing effects of 2DG, without altering
      radiosensitivity in the absence of 2DG. Furthermore, treatment with NAC partially
      reversed the 2DG-induced decreases in total glutathione content, as well as
      augmented intracellular cysteine content. Finally, the cytotoxicity and
      radiosensitizing effects of 2DG were more pronounced in v-Fos-transformed versus
      nontransformed immortalized rat cells, and this radiosensitization was also
      inhibited by treatment with NAC. These results support the hypothesis that
      exposure to 2DG causes cytotoxicity and radiosensitization via a mechanism
      involving perturbations in thiol metabolism and allows for the speculation that
      these effects may be more pronounced in transformed versus normal cells.

PMID- 12810679
TI  - c-Abl stabilizes p73 by a phosphorylation-augmented interaction.
AB  - The proapoptotic function of c-Abl is in part mediated by its functional
      interaction with p73, a p53 homologue. Although it has been shown that c-Abl
      mediated p73 activation in response to genotoxic stress is associated with an
      increase of p73 protein levels, the underlying mechanism remains unclear. We show
      here that c-Abl increases the cellular p73 abundance through a mode of
      posttranslational regulation. Analogous to its functional activation of p73, the
      kinase activity is essential for c-Abl to up-regulate p73 protein levels.
      Analysis of phosphorylation-resistant mutants of p73 reveals that the effect of c
      Abl is mediated by its direct phosphorylation on the p73 protein. Consequence to
      the phosphorylation is a marked increase of the association between c-Abl and p73
      via the binding of tyrosine-phosphorylated p73 to the c-Abl Src homology 2 (SH2)
      domain. Of functional importance of this phosphorylation-induced interaction in
      p73 stabilization is the demonstration that expression of a c-Abl SH2 domain
      peptide, which impedes phosphorylation-dependent association, results in an
      almost complete abrogation of c-Abl-dependent p73 accumulation. Importantly,
      expression of the c-Abl SH2 domain peptide also leads to an efficient inhibition
      of cisplatin-induced accumulation of endogenous p73, highlighting the biological
      significance. In keeping with its retained phosphorylation sites, the NH(2)
      terminal truncated (Delta N) isoforms of p73, which are antiapoptotic, are also
      phosphorylated and stabilized by c-Abl, suggesting a possibility that c-Abl
      contributes to either pro- or antiapoptotic process depending on the expression
      profile of p73 isoforms.

PMID- 12810680
TI  - EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity.
AB  - The EphA2 receptor tyrosine kinase is found at low levels on nontransformed adult
      breast epithelial cells but is frequently overexpressed on aggressive breast
      cancer cells. Recent studies have documented an inverse relationship between
      EphA2 and estrogen receptor expression in breast cancer cell lines. In our
      present study, we demonstrate that overexpression of EphA2 decreases estrogen
      dependence as defined using both in vitro and in vivo criteria. The EphA2
      transfected cells demonstrate increased growth in vitro and form larger and more
      aggressive tumors in vivo. EphA2 overexpression also decreases the ability of
      tamoxifen to inhibit breast cancer cell growth and tumorigenesis. These effects
      of EphA2 overexpression can be overcome by antibody-based targeting of EphA2. In
      particular, certain EphA2 antibodies can resensitize EphA2-overexpressing breast
      tumor cells to tamoxifen. These results have important implications for
      understanding the molecular basis underlying estrogen dependence and provide
      further evidence that EphA2 may provide a much-needed therapeutic target for
      breast cancer.

PMID- 12810681
TI  - Dykellic acid inhibits phorbol myristate acetate-induced matrix metalloproteinase
      9 expression by inhibiting nuclear factor kappa B transcriptional activity.
AB  - Proteolytic degradation of the extracellular matrix and tumor metastasis
      correlate with expression of endopeptidases known as matrix metalloproteinases
      (MMPs). Expression of MMPs is regulated by cytokines and signal transduction
      pathways, including those activated by phorbol myristate acetate. We found that
      dykellic acid, a fungal metabolite, significantly inhibits the phorbol myristate
      acetate-induced increase in MMP-9 expression and activity. These effects of
      dykellic acid are time- and dose-dependent, and correlate with decreased MMP-9
      promoter activity and mRNA expression. Whereas this compound does not affect DNA
      binding activity of nuclear factor kappa B (NF kappa B), dykellic acid does
      inhibit transactivation of NF kappa B. These data demonstrate a role for NF kappa
      B in the regulation of MMP-9 expression and the ability of dykellic acid to
      suppress this action of NF kappa B.

PMID- 12810682
TI  - E1A oncogene-induced sensitization of human tumor cells to innate immune defenses
      and chemotherapy-induced apoptosis in vitro and in vivo.
AB  - Expression of the adenoviral E1A oncogene induces susceptibility of neoplastic
      cells from different species to both immune-mediated and chemotherapy-induced
      cell death. These effects of E1A are easily measured in vitro using cytotoxicity
      assays. However, conventional in vivo assays of tumor development lack similar
      precision for measurement of oncogene-induced changes in tumor cell traits. E1A
      expression in p53 mutant human breast carcinoma cells sensitized them in vitro to
      diverse immunological injuries and apoptosis triggered by chemotherapeutic
      agents, as predicted from studies of rodent tumor cells. Nude mice, which possess
      innate cellular immune defenses against E1A-expressing tumor cells, were used in
      a quantitative tumor induction assay to test the in vivo correlations of E1A
      induced immunosensitivity and chemosensitivity of human tumor cells. Two
      distinct, E1A-induced breast cancer cell traits could be measured in nude mice:
      (a) increased tumor latency and (b) reduced efficiency of tumor induction. These
      results were confirmed in studies of E1A-expressing human fibrosarcoma cells. The
      results demonstrate that E1A-induced conversion of human cells from a cytolytic
      resistant to a cytolytic susceptible phenotype, as detected in vitro, translates
      into reduced tumorigenicity of cells confronted with innate immune defenses and
      exposed to chemotherapeutic agents in nude mice. However, the data also show that
      E1A expression does not completely eliminate the tumorigenicity of either
      established human tumor cells or of cells immortalized by E1A. This experimental
      approach should be useful for studies of the effects of other oncogene-related
      tumor cell traits on tumorigenicity and could be used for preclinical studies of
      different treatment strategies for human tumors.

PMID- 12810683
TI  - Bruton's tyrosine kinase is required for lipopolysaccharide-induced tumor
      necrosis factor alpha production.
AB  - Lipopolysaccharide (LPS), a product of Gram-negative bacteria, is potent mediator
      of tumor necrosis factor (TNF)alpha production by myeloid/macrophage cells.
      Inhibitors capable of blocking the signaling events that result in TNF alpha
      production could provide useful therapeutics for treating septic shock and other
      inflammatory diseases. Broad spectrum tyrosine inhibitors are known to inhibit
      TNF alpha production, however, no particular family of tyrosine kinases has been
      shown to be essential for this process. Here we show that the Bruton's tyrosine
      kinase (Btk)-deficient mononuclear cells from X-linked agammaglobulinemia
      patients have impaired LPS-induced TNF alpha production and that LPS rapidly
      induces Btk kinase activity in normal monocytes. In addition, adenoviral
      overexpression of Btk in normal human monocytes enhanced TNF alpha production. We
      examined the role of Btk in TNF alpha production using luciferase reporter
      adenoviral constructs and have established that overexpression of Btk results in
      the stabilization of TNF alpha mRNA via the 3' untranslated region. Stimulation
      with LPS also induced the activation of related tyrosine kinase, Tec, suggesting
      that the Tec family kinases are important components for LPS-induced TNF alpha
      production. This study provides the first clear evidence that tyrosine kinases of
      the Tec family, in particular Btk, are key elements of LPS-induced TNF alpha
      production and consequently may provide valuable therapeutic targets for
      intervention in inflammatory conditions.

PMID- 12810684
TI  - Differential requirement for Rel/nuclear factor kappa B family members in natural
      killer T cell development.
AB  - Natural killer T (NKT) cells have been implicated in diverse immune responses
      ranging from suppression of autoimmunity to tumor rejection. Thymus-dependent NKT
      cells are positively selected by the major histocompatibility complex class I
      like molecule CD1d, but the molecular events downstream of CD1d are still poorly
      understood. Here, we show that distinct members of the Rel/nuclear factor (NF)
      kappa B family of transcription factors were required in both hematopoietic and
      nonhematopoietic cells for normal development of thymic NKT cells. Activation of
      NF-kappa B via the classical I kappa B alpha-regulated pathway was required in a
      cell autonomous manner for the transition of NK-1.1-negative precursors that
      express the TCR V alpha 14-J alpha 18 chain to mature NK-1.1-positive NKT cells.
      The Rel/NF-kappa B family member RelB, on the other hand, had to be expressed in
      radiation resistant thymic stromal cells for the generation of early NK-1.1
      negative NKT precursors. Moreover, NF-kappa B-inducing kinase (NIK) was required
      for both constitutive thymic DNA binding of RelB and the specific induction of
      RelB complexes in vitro. Thus, distinct Rel/NF-kappa B family members in
      hematopoietic and nonhematopoietic cells regulate NKT cell development with a
      unique requirement for NIK-mediated activation of RelB in thymic stroma.

PMID- 12810685
TI  - NIK-dependent RelB activation defines a unique signaling pathway for the
      development of V alpha 14i NKT cells.
AB  - A defect in RelB, a member of the Rel/nuclear factor (NF)-kappa B family of
      transcription factors, affects antigen presenting cells and the formation of
      lymphoid organs, but its role in T lymphocyte differentiation is not well
      characterized. Here, we show that RelB deficiency in mice leads to a selective
      decrease of NKT cells. RelB must be expressed in an irradiation-resistant host
      cell that can be CD1d negative, indicating that the RelB expressing cell does not
      contribute directly to the positive selection of CD1d-dependent NKT cells. Like
      RelB-deficient mice, aly/aly mice with a mutation for the NF-kappa B-inducing
      kinase (NIK), have reduced NKT cell numbers. An analysis of NK1.1 and CD44
      expression on NKT cells in the thymus of aly/aly mice reveals a late block in
      development. In vitro, we show that NIK is necessary for RelB activation upon
      triggering of surface receptors. This link between NIK and RelB was further
      demonstrated in vivo by analyzing RelB+/- x aly/+ compound heterozygous mice.
      After stimulation with alpha-GalCer, an antigen recognized by NKT cells, these
      compound heterozygotes had reduced responses compared with either RelB+/- or
      aly/+ mice. These data illustrate the complex interplay between hemopoietic and
      nonhemopoietic cell types for the development of NKT cells, and they demonstrate
      the unique requirement of NKT cells for a signaling pathway mediated by NIK
      activation of RelB in a thymic stromal cell.

PMID- 12810686
TI  - Memory CD8+ T cells are required for protection from persistent hepatitis C virus
      infection.
AB  - Few hepatitis C virus (HCV) infections resolve spontaneously but those that do
      appear to afford protective immunity. Second infections are usually shorter in
      duration and are less likely to persist but mechanisms of virus control in immune
      individuals have not been identified. In this study we investigated whether
      memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees
      serially reinfected with the virus. Clearance of the first infection took 3-4 mo
      and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High
      frequencies of memory T cells targeting multiple HCV proteins were stable over 7
      yr of follow-up. Animals were infected for a second time to assess the protective
      role of memory T cells. In contrast to the prolonged course of the first
      infection, viremia was terminated within 14 d. Control of this second infection
      was kinetically linked to rapid acquisition of virus-specific cytolytic activity
      by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in
      blood. The importance of memory CD8+ T cells in control of HCV infection was
      confirmed by antibody-mediated depletion of this lymphocyte subset before a third
      infection. Virus replication was prolonged despite the presence of memory CD4+ T
      helper cells primed by the two prior infections and was not terminated until HCV
      specific CD8+ T cells recovered in the liver. These experiments demonstrate an
      essential role for memory CD8+ T cells in long-term protection from chronic
      hepatitis C.

PMID- 12810687
TI  - Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2+ influx,
      and NFATc translocation causing inhibition of T cell differentiation.
AB  - Transforming growth factor (TGF)-beta inhibits T cell proliferation and
      differentiation. TGF-beta has been shown to inhibit the expression of
      transcription factors such as GATA-3 and T-bet that play important roles in T
      cell differentiation. Here we show that TGF-beta inhibits T cell differentiation
      at a more proximal step. An early event during T cell activation is increased
      intracellular calcium levels. Calcium influx in activated T cells and the
      subsequent activation of transcription factors such as NFATc, events essential
      for T cell differentiation, are modulated by the Tec kinases that are downstream
      of the T cell receptor and CD28. We show that in stimulated CD4+ T cells, TGF
      beta inhibits phosphorylation and activation of the Tec kinase Itk, increase in
      intracellular Ca2+ levels, NFATc translocation, and activation of the mitogen
      activated protein kinase ERK that together regulate T cell differentiation. Our
      studies suggest that by inhibiting Itk, and consequently Ca2+ influx, TGF-beta
      limits T cell differentiation along both the Th1 and Th2 lineages.

PMID- 12810688
TI  - Fractalkine preferentially mediates arrest and migration of CD16+ monocytes.
AB  - CD16+ monocytes represent 5-10% of peripheral blood monocytes in normal
      individuals and are dramatically expanded in several pathological conditions
      including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+
      monocytes produce high levels of proinflammatory cytokines and may represent
      dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of
      CD16+ monocytes into tissues remain unknown. Here we investigate molecular
      mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and
      CD16- monocytes is mediated by distinct combinations of adhesion molecules and
      chemokine receptors. In contrast to CD16- monocytes, CD16+ monocytes expressed
      high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient
      transendothelial migration in response to fractalkine (FKN; FKN/CX3CL1) and
      stromal-derived factor 1 alpha (CXCL12) but not monocyte chemoattractant protein
      1 (CCL2). CD16+ monocytes arrested on cell surface-expressed FKN under flow with
      higher frequency compared with CD16- monocytes. These results demonstrate that
      FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest
      that recruitment of this proinflammatory monocyte subset to vessel walls via the
      CX3CR1-FKN pathway may contribute to vascular and tissue injury during
      pathological conditions.

PMID- 12810689
TI  - Unraveling a revealing paradox: Why major histocompatibility complex I-signaled
      thymocytes "paradoxically" appear as CD4+8lo transitional cells during positive
      selection of CD8+ T cells.
AB  - The mechanism by which T cell receptor specificity determines the outcome of the
      CD4/CD8 lineage decision in the thymus is not known. An important clue is the
      fact that major histocompatibility complex (MHC)-I-signaled thymocytes
      paradoxically appear as CD4+8lo transitional cells during their differentiation
      into CD8+ T cells. Lineage commitment is generally thought to occur at the CD4+8+
      (double positive) stage of differentiation and to result in silencing of the
      opposite coreceptor gene. From this perspective, the appearance of MHC-I-signaled
      thymocytes as CD4+8lo cells would be due to effects on CD8 surface protein
      expression, not CD8 gene expression. But contrary to this perspective, this study
      demonstrates that MHC-I-signaled thymocytes appear as CD4+8lo cells because of
      transient down-regulation of CD8 gene expression, not because of changes in CD8
      surface protein expression or distribution. This study also demonstrates that
      initial cessation of CD8 gene expression in MHC-I-signaled thymocytes is not
      necessarily indicative of commitment to the CD4+ T cell lineage, as such
      thymocytes retain the potential to differentiate into CD8+ T cells. These results
      challenge classical concepts of lineage commitment but fulfill predictions of the
      kinetic signaling model.

PMID- 12810690
TI  - B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism.
AB  - B7H1 (PDL1) and B7DC (PDL2) are two new members of the B7 family that can
      interact with PD-1, a putative negative regulator for immune function. Recent
      studies have provided evidence for inhibitory functions of both members via PD-1.
      Meanwhile, compelling evidence exists for costimulatory function of both members.
      Here we demonstrate that expression of B7DC on the tumor cells promotes CD8 T
      cell-mediated rejection of tumor cells, at both the induction and effector phase
      of antitumor immunity. Moreover, B7DC binds to PD-1(-/-) cells and enhances T
      cell killing in a PD-1-independent mechanism. Our results demonstrate a novel
      pathway for B7DC to promote tumor immunity and may reconcile the apparently
      contradictory findings on the function of B7DC.

PMID- 12810691
TI  - Tumors acquire inhibitor of apoptosis protein (IAP)-mediated apoptosis resistance
      through altered specificity of cytosolic proteolysis.
AB  - Many tumors overexpress members of the inhibitor of apoptosis protein (IAP)
      family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of
      caspases, and are degraded by the proteasome to allow further progression of
      apoptosis. Here we show that tumor cells can alter the specificity of cytosolic
      proteolysis in order to acquire apoptosis resistance, which promotes formation of
      rapidly growing tumors. Survival of tumor cells with low proteasomal activity can
      occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a
      large subtilisin-like peptidase that complements proteasomal activity. We find
      that this state leaves tumor cells unable of effectively degrading IAPs, and that
      cells in this state form rapidly growing tumors in vivo. We also find, in studies
      of apoptosis resistant cells derived from large in vivo tumors, that these have
      acquired an altered peptidase activity, with up-regulation of TPP II activity and
      decreased proteasomal activity. Importantly, we find that growth of subcutaneous
      tumors is limited by maintenance of the apoptosis resistant phenotype. The
      apoptosis resistant phenotype was reversed by increased expression of
      Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible
      mechanism in regulation of apoptosis resistance that drives tumor progression in
      vivo. These data are relevant in relation to the multitude of therapy-resistant
      clinical tumors that have increased levels of IAP molecules.

PMID- 12810692
TI  - Stimulus-dependent deacylation of bacterial lipopolysaccharide by dendritic
      cells.
AB  - We describe here a previously unrecognized property of dendritic cells (DCs), the
      ability to deacylate the lipid A moiety of gram-negative bacterial LPSs. Both
      immature DCs of the XS52 cell line and bone marrow-derived DCs produce
      acyloxyacyl hydrolase, an enzyme that detoxifies LPS by selectively removing the
      secondary acyl chains from lipid A. Acyloxyacyl hydrolase expression decreased
      when DCs were incubated with IL-4, IL-1 beta, TNF alpha, and an agonistic CD40
      antibody (maturation cocktail), and increased after treatment with LPS, CpG
      oligodeoxynucleotides, or a gram-positive bacterium (Micococcus luteus).
      Maturation cocktail treatment also diminished, whereas LPS treatment enhanced or
      maintained the cells' ability to kill Escherichia coli, deacylate LPS, and
      degrade bacterial protein. Enzymatic deacylation of LPS is an intrinsic,
      regulated mechanism by which DCs may modulate host responses to this potent
      bacterial agonist.

PMID- 12810693
TI  - Multistep nature of microvascular recruitment of ex vivo-expanded embryonic
      endothelial progenitor cells during tumor angiogenesis.
AB  - Tissue neovascularization involves recruitment of circulating endothelial
      progenitor cells that originate in the bone marrow. Here, we show that a class of
      embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low),
      which were isolated at E7.5 of mouse development at the onset of vasculogenesis,
      retain their ability to contribute to tumor angiogenesis in the adult. Using
      intravital fluorescence videomicroscopy, we further defined the multistep process
      of embryonic endothelial progenitor cell (eEPC) homing and incorporation.
      Circulating eEPCs are specifically arrested in "hot spots" within the tumor
      microvasculature, extravasate into the interstitium, form multicellular clusters,
      and incorporate into functional vascular networks. Expression analysis and in
      vivo blocking experiments provide evidence that the initial cell arrest of eEPC
      homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1.
      This paper provides the first in vivo insights into the mechanisms of endothelial
      progenitor cell recruitment and, thus, indicates novel ways to interfere with
      pathological neovascularization.

PMID- 12810695
TI  - Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell
      carcinoma: a cytokine working group randomized trial.
AB  - PURPOSE: This prospective, randomized, controlled phase III trial assessed high
      dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal
      cell carcinoma (RCC). PATIENTS AND METHODS: Eligibility requirements were
      resected locally advanced (LA; T3b-4 or N1-3) or metastatic (M1) RCC, no prior
      systemic therapy, and excellent organ function. Randomized assignment was to one
      course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19
      [maximum 28 doses]) or observation. The study was designed and powered to show an
      improvement in predicted 2-year disease-free survival (DFS) from 40% for the
      observation group to 70% for the treatment group. The accrual goal was 68
      patients with LA disease, with 34 patients per treatment arm. Metastasectomy
      patients were to be analyzed separately because of their unpredictable natural
      history. RESULTS: Sixty-nine patients were enrolled onto the study (44 LA and 25
      M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious
      adverse events or treatment-related deaths occurred. Early closure occurred when
      an interim analysis determined that the 30% improvement in 2-year DFS could not
      be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2
      experienced relapse, compared with 15 of 23 patients in the observation arm (P
      =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths
      occurred in the observation arm (P =.38). Analysis including metastasectomy
      patients made no difference in DFS or overall survival. CONCLUSION: One course of
      high-dose bolus IL-2, though feasible, did not produce the ambitious clinically
      meaningful benefit anticipated when administered postoperatively to patients with
      resected high-risk RCC.

PMID- 12810694
TI  - H2AX is required for recombination between immunoglobulin switch regions but not
      for intra-switch region recombination or somatic hypermutation.
AB  - Changes in chromatin structure induced by posttranslational modifications of
      histones are important regulators of genomic function. Phosphorylation of histone
      H2AX promotes DNA repair and helps maintain genomic stability. Although B cells
      lacking H2AX show impaired class switch recombination (CSR), the precise role of
      H2AX in CSR and somatic hypermutation (SHM) has not been defined. We show that
      H2AX is not required for SHM, suggesting that the processing of DNA lesions
      leading to SHM is fundamentally different from CSR. Impaired CSR in H2AX-/- B
      cells is not due to alterations in switch region transcription, accessibility, or
      aberrant joining. In the absence of H2AX, short-range intra-switch region
      recombination proceeds normally while long-range inter-switch region
      recombination is impaired. Our results suggest a role for H2AX in regulating the
      higher order chromatin remodeling that facilitates switch region synapsis.

PMID- 12810696
TI  - ADP ribosylation factor 6 is activated and controls membrane delivery during
      phagocytosis in macrophages.
AB  - Engulfment of particles by phagocytes is induced by their interaction with
      specific receptors on the cell surface, which leads to actin polymerization and
      the extension of membrane protrusions to form a closed phagosome. Membrane
      delivery from internal pools is considered to play an important role in pseudopod
      extension during phagocytosis. Here, we report that endogenous ADP ribosylation
      factor 6 (ARF6), a small GTP-binding protein, undergoes a sharp and transient
      activation in macrophages when phagocytosis was initiated via receptors for the
      Fc portion of immunoglobulins (FcRs). A dominant-negative mutant of ARF6 (T27N
      mutation) dramatically affected FcR-mediated phagocytosis. Expression of ARF6
      T27N lead to a reduction in the focal delivery of vesicle-associated membrane
      protein 3+ endosomal recycling membranes at phagocytosis sites, whereas actin
      polymerization was unimpaired. This resulted in an early blockade in pseudopod
      extension and accumulation of intracellular vesicles, as observed by electron
      microscopy. We conclude that ARF6 is a major regulator of membrane recycling
      during phagocytosis.

PMID- 12810697
TI  - Perilipin A is essential for the translocation of hormone-sensitive lipase during
      lipolytic activation.
AB  - Akey step in lipolytic activation of adipocytes is the translocation of hormone
      sensitive lipase (HSL) from the cytosol to the surface of the lipid storage
      droplet. Adipocytes from perilipin-null animals have an elevated basal rate of
      lipolysis compared with adipocytes from wild-type mice, but fail to respond
      maximally to lipolytic stimuli. This defect is downstream of the beta-adrenergic
      receptor-adenylyl cyclase complex. Now, we show that HSL is basally associated
      with lipid droplet surfaces at a low level in perilipin nulls, but that
      stimulated translocation from the cytosol to lipid droplets is absent in
      adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have
      also reconstructed the HSL translocation reaction in the nonadipocyte Chinese
      hamster ovary cell line by introduction of GFP-tagged HSL with and without
      perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid
      droplets only in cells that express fully phosphorylatable perilipin A,
      confirming that perilipin is required to elicit the HSL translocation reaction.
      Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A,
      these two proteins cooperate to produce a more rapidly accelerated lipolysis than
      do cells that express either of these proteins alone, indicating that lipolysis
      is a concerted reaction mediated by both protein kinase A-phosphorylated HSL and
      perilipin A.

PMID- 12810698
TI  - Adhesion-independent mechanism for suppression of tumor cell invasion by E
      cadherin.
AB  - Loss of E-cadherin expression or function in tumors leads to a more invasive
      phenotype. In this study, we investigated whether the invasion suppressor
      activity of E-cadherin is mediated directly by tighter physical cell adhesion,
      indirectly by sequestering beta-catenin and thus antagonizing beta-catenin/T cell
      factor (TCF) signaling, or by other signaling pathways. To distinguish
      mechanisms, we expressed wild-type E-cadherin and various E-cadherin mutants in
      invasive E-cadherin-negative human breast (MDA-MB-231) and prostate (TSU-Pr1)
      epithelial carcinoma cell lines using a tetracycline-inducible system. Our data
      confirm that E-cadherin inhibits human mammary and prostate tumor cell invasion.
      We find that adhesion is neither necessary nor sufficient for suppressing cancer
      invasion. Rather, the invasion suppressor signal is mediated through the beta
      catenin-binding domain of the E-cadherin cytoplasmic tail but not through the
      p120ctn-binding domain. beta-catenin depletion also results in invasion
      suppression. However, alteration in the beta-catenin/TCF transcriptional
      regulation of target genes is not required for the invasion suppressor activity
      of E-cadherin, suggesting the involvement of other beta-catenin-binding proteins.

PMID- 12810699
TI  - Formin-dependent actin assembly is regulated by distinct modes of Rho signaling
      in yeast.
AB  - Formins are actin filament nucleators regulated by Rho-GTPases. In budding yeast,
      the formins Bni1p and Bnr1p direct the assembly of actin cables, which guide
      polarized secretion and growth. From the six yeast Rho proteins (Cdc42p and Rho1
      5p), we have determined that four participate in the regulation of formin
      activity. We show that the essential function of Rho3p and Rho4p is to activate
      the formins Bni1p and Bnr1p, and that activated alleles of either formin are able
      to bypass the requirement for these Rho proteins. Through a separate signaling
      pathway, Rho1p is necessary for formin activation at elevated temperatures,
      acting through protein kinase C (Pkc1p), the major effector for Rho1p signaling
      to the actin cytoskeleton. Although Pkc1p also activates a MAPK pathway, this
      pathway does not function in formin activation. Formin-dependent cable assembly
      does not require Cdc42p, but in the absence of Cdc42p function, cable assembly is
      not properly organized during initiation of bud growth. These results show that
      formin function is under the control of three distinct, essential Rho signaling
      pathways.

PMID- 12810700
TI  - VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia.
AB  - Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel
      formation and function. It controls several processes in endothelial cells, such
      as proliferation, survival, and migration, but it is not known how these are
      coordinately regulated to result in more complex morphogenetic events, such as
      tubular sprouting, fusion, and network formation. We show here that VEGF-A
      controls angiogenic sprouting in the early postnatal retina by guiding filopodial
      extension from specialized endothelial cells situated at the tips of the vascular
      sprouts. The tip cells respond to VEGF-A only by guided migration; the
      proliferative response to VEGF-A occurs in the sprout stalks. These two cellular
      responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2.
      Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is
      regulated by its concentration. Thus, vessel patterning during retinal
      angiogenesis depends on the balance between two different qualities of the
      extracellular VEGF-A distribution, which regulate distinct cellular responses in
      defined populations of endothelial cells.

PMID- 12810701
TI  - The localization and phosphorylation of p47 are important for Golgi disassembly
      assembly during the cell cycle.
AB  - In mammalian cells, the Golgi apparatus is disassembled at the onset of mitosis
      and reassembled at the end of mitosis. This disassembly-reassembly is generally
      believed to be essential for the equal partitioning of Golgi into two daughter
      cells. For Golgi disassembly, membrane fusion, which is mediated by NSF and p97,
      needs to be blocked. For the NSF pathway, the tethering of p115-GM130 is
      disrupted by the mitotic phosphorylation of GM130, resulting in the inhibition of
      NSF-mediated fusion. In contrast, the p97/p47 pathway does not require p115-GM130
      tethering, and its mitotic inhibitory mechanism has been unclear. Now, we have
      found that p47, which mainly localizes to the nucleus during interphase, is
      phosphorylated on Serine-140 by Cdc2 at mitosis. The phosphorylated p47 does not
      bind to Golgi membranes. An in vitro assay shows that this phosphorylation is
      required for Golgi disassembly. Microinjection of p47(S140A), which is unable to
      be phosphorylated, allows the cell to keep Golgi stacks during mitosis and has no
      effect on the equal partitioning of Golgi into two daughter cells, suggesting
      that Golgi fragmentation-dispersion may not be obligatory for equal partitioning
      even in mammalian cells.

PMID- 12810703
TI  - Lipolysis: more than just a lipase.
AB  - Successful adaptation to starvation in mammals depends heavily on the regulated
      mobilization of fatty acids from triacylglycerols stored in adipose tissue.
      Although it has long been recognized that cyclic AMP represents the critical
      second messenger and hormone-sensitive lipase (HSL)**Abbreviations used in this
      paper: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive
      lipase; PKA, protein kinase A; TAG, triacylglycerol. the rate-determining enzyme
      for lipolysis, simple activation of the enzyme has failed to account for the
      robust augmentation of fatty release in response to physiological agonists. In
      this issue, Sztalryd et al. (2003) provide convincing support to the notion that
      the subcellular compartmentalization of lipase also regulates lipolysis, and,
      more importantly, that proteins other than HSL are localized to the lipid droplet
      and are indispensable for its optimal hydrolysis.

PMID- 12810702
TI  - Ergosterol is required for targeting of tryptophan permease to the yeast plasma
      membrane.
AB  - It was known that the uptake of tryptophan is reduced in the yeast erg6 mutant,
      which is defective in a late step of ergosterol biosynthesis. Here, we show that
      this is because the high affinity tryptophan permease Tat2p is not targeted to
      the plasma membrane. In wild-type cells, the plasma membrane localization of
      Tat2p is regulated by the external tryptophan concentration. Tat2p is transported
      from the Golgi apparatus to the vacuole at high tryptophan, and to the plasma
      membrane at low tryptophan. However, in the erg6 mutant, Tat2p is missorted to
      the vacuole at low tryptophan. The plasma membrane targeting of Tat2p is
      dependent on detergent-insoluble membrane domains, suggesting that sterol affects
      the sorting through the organization of lipid rafts. The erg6 mutation also
      caused missorting to the multivesicular body pathway in late endosomes. Thus,
      sterol composition is crucial for protein sorting late in the secretory pathway.
      Tat2p is subject to polyubiquitination, which acts as a vacuolar-targeting
      signal, and the inhibition of this process suppresses the Tat2p sorting defects
      of the erg6 mutant. The sorting mechanisms of Tat2p that depend on both sterol
      and ubiquitin will be discussed.

PMID- 12810704
TI  - Selective interactions between helix VIII of the human mu-opioid receptors and
      the C terminus of periplakin disrupt G protein activation.
AB  - Analysis of interactions between the C-terminal tail of the MOP-1 and MOP-1A
      variants of the human mu-opioid receptor with proteins derived from a human brain
      cDNA library resulted in identification of the actin and intermediate filament
      binding protein periplakin. Mapping of this interaction indicated that the
      predicted fourth intracellular loop/helix VIII of the receptor interacts with the
      C-terminal rod and linker region of periplakin. Periplakin is widely expressed in
      the central nervous system of both man and rat and demonstrated an overlapping
      but not identical distribution with mu-opioid (MOP) receptors. Co-expression of
      periplakin with MOP-1 or a MOP-1-eYFP fusion construct in HEK293 cells did not
      interfere with agonist-mediated internalization of the receptor. When co
      expressed with a MOP-1-Gi1 alpha fusion protein periplakin significantly reduced
      the capacity of the agonist to stimulate binding of 35S-labeled guanosine 5'-3-O
      (thio)triphosphate ([35S]GTP gamma S) to the receptor-associated G protein. By
      contrast, periplakin did not interfere with agonist-stimulation of [35S]GTP gamma
      S binding to either an alpha 2A-adrenoreceptor-Gi1 alpha fusion protein or a
      beta2-adrenoreceptor-Gs alpha fusion protein, indicating its selectivity of
      function. This represents the first example of an opioid receptor-interacting
      protein that functions to disrupt agonist-mediated G protein activation.

PMID- 12810705
TI  - Acylated cholesteryl galactoside as a novel immunogenic motif in Borrelia
      burgdorferi sensu stricto.
AB  - Borrelia burgdorferi sensu lato is the causing agent of Lyme disease, an
      infectious disease frequently occurring in the United States, Europe, and
      Northern Asia. Currently, diagnosis of and vaccination strategies against this
      pathogen are exclusively based on proteinaceous structures. Here we report on a
      novel class of immunogenic glycolipids purified from B. burgdorferi sensu stricto
      B31. Employing a butanol/water extraction procedure with subsequent Bligh/Dyer
      extraction of the organic phase, thin layer chromatography analysis revealed the
      presence of three distinct glycolipids, which were chemically analyzed employing
      combined gas-liquid chromatography/mass spectroscopy, matrix-assisted laser
      desorption/ionization mass spectrometry, and NMR. We identified acylated
      cholesteryl galactoside (ACG) next to cholesteryl galactoside and alpha
      monogalactosyl-diacylglycerol. After extensive purification, the glycolipids
      investigated failed to cause proinflammatory responses in human cells transfected
      with human toll-like receptor (TLR)-2 or -4. However, we observed a marked
      recognition of ACG by sera derived from patients suffering from Lyme disease.
      These data indicate that newly described ACG is involved in developing host
      immunity during Lyme disease and thus may be useful for diagnosis and
      vaccination.

PMID- 12810706
TI  - Modification of CCAAT/enhancer-binding protein-beta by the small ubiquitin-like
      modifier (SUMO) family members, SUMO-2 and SUMO-3.
AB  - CCAAT/enhancer-binding protein-beta (C/EBP beta) activator isoforms, C/EBP beta-1
      and C/EBP beta-2, differ by only 23 amino acids in the human; however, evidence
      is accumulating that these transcription factors are functionally distinct. Here
      we demonstrate that C/EBP beta-1, but not C/EBP beta-2, is conjugated to the
      small ubiquitin-like modifier (SUMO) family members, SUMO-2 and SUMO-3 despite
      the fact that the SUMO target consensus is present in both isoforms of this
      transcription factor. This conjugation is dependent on the integrity of the
      extreme N terminus of C/EBP beta-1 and requires lysine 173 in the human protein.
      Furthermore, mutation of this lysine relieves the repression of the cyclin D1
      promoter by C/EBP beta-1 without altering the subnuclear localization of C/EBP
      beta-1. The sumoylation of C/EBP beta-1 is likely to be important in the
      functional differences observed between C/EBP beta-1 and C/EBP beta-2.

PMID- 12810707
TI  - Peroxisome proliferator-activated receptor alpha induces hepatic expression of
      the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme.
AB  - Glucuronidation, a major metabolic pathway for a large variety of endobiotics and
      xenobiotics, is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase
      (UGT) family. Among UGT enzymes, UGT2B4 conjugates a large variety of endogenous
      and exogenous molecules and is considered to be the major bile acid conjugating
      UGT enzyme in human liver. In the present study, we identify UGT2B4 as a novel
      target gene of the nuclear receptor peroxisome proliferator-activated receptor
      alpha (PPAR alpha), which mediates the hypolipidemic action of fibrates.
      Incubation of human hepatocytes or hepatoblastoma HepG2 and Huh7 cells with
      synthetic PPAR alpha agonists, fenofibric acid, or Wy 14643 resulted in an
      increase of UGT2B4 mRNA levels. Furthermore, treatment of HepG2 cells with Wy
      14643 induced the glucuronidation of hyodeoxycholic acid, a specific bile acid
      UGT2B4 substrate. Analysis of UGT2B mRNA and protein levels in PPAR alpha wild
      type and null mice revealed that PPAR alpha regulates both basal and fibrate
      induced expression of these enzymes in rodents also. Finally, a PPAR response
      element was identified in the UGT2B4 promoter by site-directed mutagenesis and
      electromobility shift assays. These results demonstrate that PPAR alpha agonists
      may control the catabolism of cytotoxic bile acids and reinforce recent data
      indicating that PPAR alpha, which has been largely implicated in the control of
      lipid and cholesterol metabolism, is also an important modulator of the
      metabolism of endobiotics and xenobiotics in human hepatocytes.

PMID- 12810708
TI  - Endotoxins stimulate neutrophil adhesion followed by synthesis and release of
      platelet-activating factor in microparticles.
AB  - Lipopolysaccharides and triacyl-cysteine-modified proteins of Gram-negative and
      positive organisms are potent endotoxins. Animal models show that the receptor
      for platelet-activating factor (PAF) is responsible for many of the deleterious
      effects of endotoxin, where regulated, localized PAF production localizes the
      inflammatory response. In contrast, biologically active analogs of PAF (PAF-like
      lipids) are generated by oxidative attack on phospholipids by chemical reactions
      that are unregulated and unlocalized. The identity and distribution of the PAF
      receptor ligand in endotoxemia is unknown. We found human polymorphonuclear
      leukocytes (PMNs) were a significant source of PAF receptor agonists after
      stimulation by either class of endotoxin. Production of PAF receptor agonists
      required that the PMN adhere to a surface, and adhesion (and therefore
      accumulation of PAF-like bioactivity) in response to endotoxic stimulation was
      delayed for several minutes. PAF-like oxidized phospholipids were found by mass
      spectroscopy, but biosynthetic PAF accounted for most of the phospholipid
      agonists arising from endotoxic stimulation. A significant portion of the PAF
      made by PMNs was secreted, in contrast to its near complete retention by other
      inflammatory cells. Endotoxic stimulation induced a respiratory burst with the
      production of superoxide and the formation and shedding of microparticles. Free
      and microparticle-bound PAF appeared in the media, and blocking microvesiculation
      with calpeptin blocked PAF release. The released material activated platelets,
      and platelets co-aggregated with endotoxin-stimulated PMNs. Adherent PMNs
      therefore behave differently than suspended cells and are a significant source of
      free PAF after endotoxin exposure. Leukocytes can couple endotoxic challenge to
      the widespread circulatory and inflammatory effects of endotoxin.

PMID- 12810709
TI  - Ligand-dependent inhibition of B16 melanoma cell migration and invasion via
      endogenous S1P2 G protein-coupled receptor. Requirement of inhibition of cellular
      RAC activity.
AB  - We investigated mechanisms for inhibition of B16 melanoma cell migration and
      invasion by sphingosine-1-phosphate (S1P), which is the ligand for the Edg family
      G protein-coupled receptors and also implicated as an intracellular second
      messenger. S1P, dihydro-S1P, and sphingosylphosphorylcholine inhibited B16 cell
      migration and invasion with the relative potencies expected as S1P2 receptor
      agonists. The S1P2-selective antagonist JTE013 completely abolished the responses
      to these agonists. In addition, JTE013 abrogated the inhibition by sphingosine,
      which is the S1P precursor but not an agonist for S1P receptors, indicating that
      the sphingosine effects were mediated via S1P2 stimulation, most likely by S1P
      that was converted from sphingosine. S1P induced inhibition and activation,
      respectively, of Rac and RhoA in B16 cells, which were abrogated by JTE013.
      Adenovirus-mediated expression of N17Rac mimicked S1P inhibition of migration,
      whereas C3 toxin pretreatment, but not Rho kinase inhibitors, reversed the S1P
      inhibition. Overexpression of S1P2 sensitized, and that of either S1P1 or S1P3
      desensitized, B16 cells to S1P inhibition of Rac and migration. In JTE013
      pretreated, S1P3-overexpressing B16 cells, S1P stimulated cellular RhoA but
      failed to inhibit either Rac or migration, indicating that RhoA stimulation
      itself is not sufficient for inhibition of migration. These results provide
      compelling evidence that endogenously expressed S1P2 negatively regulates cell
      motility and invasion through ligand-dependent reciprocal regulation of cellular
      Rac and RhoA activities. In the presence of JTE013, S1P instead stimulated Rac
      and migration in B16 cells that overexpress either S1P1 or S1P3, unveiling
      counteractions between S1P2 and S1P1 or S1P3 chemotactic receptor.

PMID- 12810710
TI  - Equilibrative nucleoside transporters of Arabidopsis thaliana. cDNA cloning,
      expression pattern, and analysis of transport activities.
AB  - Equilibrative nucleoside transporters (ENTs) occur in diverse organisms. In the
      model plant Arabidopsis thaliana, eight potential ENTs (AtENTs) have been
      predicted by genome sequencing. We here report the cloning of the cDNAs for
      AtENTs 2, 3, 4, 6, 7, and 8. Conceptual translation of the cDNAs of AtENTs 2, 3,
      4, 6, 7, and 8 yielded polypeptides possessing strong similarities to ENTs
      characterized previously. Eleven putative transmembrane domains were identified
      in each of the six AtENTs. In suspension cells, the transcription of AtENTs 1, 3,
      4, 6, and 8 was increased by two treatments (nitrogen deprivation, application of
      5-fluorouracil and methotrexate) that inhibited the de novo pathway of nucleotide
      synthesis, indicating that multiple members of the Arabidopsis ENT family may
      function in the salvage pathway of nucleotide synthesis. Except for AtENT1, the
      transcription of the remaining six AtENTs showed varying degrees of organ
      specificity. However, all seven AtENTs were expressed in the leaf and flower. In
      plant, insect, and yeast cells, ectopically expressed AtENT3 was targeted to the
      plasma membrane. AtENT3 expressed in yeast cells transported adenosine and
      uridine with high affinity. Furthermore, the activities of AtENT3 appear not to
      require a transmembrane proton gradient because protonophores did not abolish
      adenosine or uridine transport. In competition experiments, the transport of
      [3H]adenosine by AtENT3 was most significantly inhibited by a number of different
      purine and pyrimidine nucleosides and 2'-deoxynucleosides, although certain
      nucleobases and nucleotides were also found to have some inhibitory effect. This
      indicates that AtENT3 may possess broad substrate specificity. Adenosine and
      uridine transport by AtENT3, although partly sensitive to the vasodilator drugs
      dilazep and dipyridamole, was resistant to the nucleoside analogue
      nitrobenzylmercaptopurine ribonucleoside. We conclude that AtENT3 represents the
      first ei type ENT characterized from higher plants. The potential functions of
      ENTs in the biology of A. thaliana are discussed.

PMID- 12810711
TI  - Characterization of the interactions within the mazEF addiction module of
      Escherichia coli.
AB  - In bacteria, programmed cell death is mediated through the unique genetic system
      called "addiction module," which consists of a pair of genes encoding a stable
      toxin and an unstable antitoxin. The mazEF system is known as an addiction module
      located on the Escherichia coli chromosome. MazF is a stable toxin, and MazE is a
      labile antitoxin interacting with MazF to form a complex. MazE and the MazE-MazF
      complex can bind to the mazEF promoter region to regulate the mazEF expression.
      Here we show that the binding of purified (His)6MazE to the mazEF promoter DNA
      was enhanced by MazF. The site-directed mutations at the conserved amino acid
      residues in MazE N-terminal region (K7A, R8A, S12A, and R16A) disrupted the DNA
      binding ability of both (His)6MazE and the MazE-MazF-(His)6 complex, suggesting
      that MazE binds to the mazEF promoter DNA through the N-terminal domain. The
      ratio of MazE to MazF(His)6 in the MazE-MazF(His)6 complex is about 1:2. Because
      both MazE and MazF-(His)6 exist as dimers by themselves, the MazE-MazF-(His)6
      complex (76.9 kDa) is predicted to consist of one MazE dimer and two MazF(His)6
      dimers. The interaction between MazE and MazF was also characterized with the
      yeast two-hybrid system. It was found that the region from residues 38 to 75 of
      MazE was required for its binding to MazF. Site-directed mutagenesis at this
      region revealed that Leu55 and Leu58 play an important role in the MazE-MazF
      complex formation but not in MazE binding to the mazEF promoter DNA. The present
      results demonstrate that MazE is composed of two domains, the N-terminal DNA
      binding domain and the C-terminal domain interacting with MazF.

PMID- 12810712
TI  - Crystal structure of the Yersinia protein-tyrosine phosphatase YopH complexed
      with a specific small molecule inhibitor.
AB  - The pathogenic bacteria Yersinia are causative agents in human diseases ranging
      from gastrointestinal syndromes to bubonic plague. There is increasing risk of
      misuse of infectious agents, such as Yersinia pestis, as weapons of terror as
      well as instruments of warfare for mass destruction. Because the phosphatase
      activity of the Yersinia protein tyrosine phosphatase, YopH, is essential for
      virulence in the Yersinia pathogen, potent and selective YopH inhibitors are
      expected to serve as novel anti-plague agents. We have identified a specific YopH
      small molecule inhibitor, p-nitrocatechol sulfate (pNCS), which exhibits a Ki
      value of 25 microM for YopH and displays a 13-60-fold selectivity in favor of
      YopH against a panel of mammalian PTPs. To facilitate the understanding of the
      underlying molecular basis for tight binding and specificity, we have determined
      the crystal structure of YopH in complex with pNCS at a 2.0-A resolution. The
      structural data are corroborated by results from kinetic analyses of the
      interactions of YopH and its site-directed mutants with pNCS. The results show
      that while the interactions of the sulfuryl moiety and the phenyl ring with the
      YopH active site contribute to pNCS binding affinity, additional interactions of
      the hydroxyl and nitro groups in pNCS with Asp-356, Gln-357, Arg-404, and Gln-446
      are responsible for the increased potency and selectivity. In particular, we note
      that residues Arg-404, Glu-290, Asp-356, and a bound water (WAT185) participate
      in a unique H-bonding network with the hydroxyl group ortho to the sulfuryl
      moiety, which may be exploited to design more potent and specific YopH
      inhibitors.

PMID- 12810713
TI  - Expression of polyglutamine-expanded huntingtin induces tyrosine phosphorylation
      of N-methyl-D-aspartate receptors.
AB  - In our previous studies, we found that expression of polyglutamine-expanded
      huntingtin in HN33 cells induced sensitization of N-methyl-D-aspartate (NMDA)
      receptors (Sun, Y., Savinainen, A., and Liu, Y. F. (2001) J. Biol. Chem. 276,
      24713-24718). Following this study, we investigated whether tyrosine
      phosphorylation of NMDA receptors might contribute to the altered property of the
      receptors. Expression of polyglutamine-expanded huntingtin induced elevation of
      phosphorylated or activated Src and increased targeting of PSD-95 (post-synaptic
      density 95) and activated Src to cell surface membrane. Expression of the mutated
      huntingtin also induced tyrosine phosphorylation of NR2B (NMDA receptor 2B)
      subunits, and co-expression of PSD-95 enhanced the phosphorylation. Treatment of
      SU6656 (a specific Src inhibitor) or co-expression of a mutated NR2B subunit with
      mutations of all three major tyrosine phosphorylation sites significantly
      attenuated neuronal toxicity induced by the mutated huntingtin. Addition of AP-5
      did not further inhibit the neuronal toxicity. Taken together, our studies show
      that polyglutamine-expanded huntingtin increases tyrosine phosphorylation of NMDA
      receptors via PSD-95 and Src, and increased tyrosine phosphorylation may
      contribute to the sensitization of the receptors mediated by polyglutamine
      expanded huntingtin.

PMID- 12810714
TI  - 5-Chlorouracil, a marker of DNA damage from hypochlorous acid during
      inflammation. A gas chromatography-mass spectrometry assay.
AB  - Hypochlorous acid (HOCl), generated from H2O2 and Cl- by myeloperoxidase in
      activated neutrophils, causes tissue damage during inflammation. We have
      developed a simple, sensitive (approximately 0.2 fmol on column) and specific GC
      MS assay for the detection of 5-chlorouracil (5-ClUra), a signature product of
      HOCl-mediated damage to nucleobases. In this assay, 5-ClUra is released from
      isolated DNA by a digestion with nuclease P1, alkaline phosphatase, and thymidine
      phosphorylase (TP), or from chlorinated nucleosides in biological fluids by TP.
      The freed 5-ClUra is derivatized with 3, 5-bis-(trifluoromethyl)-benzyl bromide,
      which is detected by negative chemical ionization mass spectrometry. The assay
      can be used to simultaneously detect other halogenated uracils including
      bromouracil. Using this assay, we showed that 5-ClUra is generated by the
      reaction of low micromolar HOCl with (deoxy)cytidine, (deoxy)uridine, and DNA. In
      cell cultures, an increase of 5-ClUra was detected in DNA when cells were treated
      with sublethal doses of HOCl and allowed to proliferate. The elevation of 5-ClUra
      was markedly accentuated when physiologically relevant concentrations of
      (deoxy)uridine, (deoxy) cytidine, uracil, or cytosine were present in the medium
      during HOCl treatment. In the carrageenan-induced inflammation model in rats,
      chlorinated nucleosides was significantly increased, compared with controls, in
      the exudate fluid isolated from the inflammation site. Our study provides the
      direct evidence that chlorinated nucleosides are found in the inflammation site
      and can be incorporated in DNA during cell/tissue proliferation. These findings
      may be relevant to the carcinogenesis associated with chronic inflammation.

PMID- 12810715
TI  - Structure and interfacial properties of human apolipoprotein A-V.
AB  - Apolipoprotein A-V (apoA-V), the newest member of the plasma apolipoprotein
      family, was recently discovered by comparison of the mouse and human genomes.
      Studies in rodents and population surveys of human apoA-V polymorphisms have
      noted a strong effect of apoA-V on plasma triglyceride levels. Toward the
      elucidation of the biologic function of apoA-V, we used spectroscopic and surface
      chemistry techniques to probe its structure and interfacial activity. Computer
      assisted sequence analysis of apoA-V predicts that it is very hydrophobic,
      contains a significant amount of alpha-helical secondary structure, and probably
      is composed of discrete structural regions with varying degrees of lipid
      affinity. Fluorescence spectroscopy of recombinant human apoA-V provided evidence
      of tertiary folding, and light scattering studies indicated that apoA-V
      transforms dimyristoylphosphatidylcholine vesicles into discoidal complexes with
      an efficiency similar to that of apoA-I. Surface chemistry techniques revealed
      that apoA-V displays high affinity, low elasticity, and slow binding kinetics at
      hydrophobic interfaces, properties we propose may retard triglyceride-rich
      particle assembly. Metabolic labeling and immunofluorescence studies of COS-1
      cells transfected with human apoA-V demonstrated that apoA-V is poorly secreted,
      remains associated with the endoplasmic reticulum, and does not traffic to the
      Golgi. Given that overexpression of the apoA-V gene lowers plasma triglycerides
      in mice, these data together suggest that apoA-V may function intracellularly to
      modulate hepatic VLDL synthesis and/or secretion.

PMID- 12810717
TI  - Rac1 function is required for Src-induced transformation. Evidence of a role for
      Tiam1 and Vav2 in Rac activation by Src.
AB  - The proto-oncogene c-Src has been implicated in the development and progression
      of a number of human cancers including those of colon and breast. Accumulating
      evidence indicates that activated alleles of Src may induce cell transformation
      through Ras-ERK-dependent and -independent pathways. Here we show that Rac1
      activity is strongly elevated in Src-transformed cells and that this small G
      protein is a critical component of the pathway connecting oncogenic Src with cell
      transformation. We further show that Vav2 and the ubiquitously expressed Rac1
      guanine nucleotide exchange factor Tiam1 are phosphorylated in tyrosine residues
      in cells transfected with active and oncogenic Src. Moreover, phosphorylation of
      Tiam1 in cells treated with pervanadate, a potent inhibitor of tyrosine
      phosphatases, was partially inhibited by the Src inhibitor SU6656. Using
      truncated mutants of Tiam1, we demonstrate that multiple sites can be tyrosine
      phosphorylated by Src. Furthermore, Tiam1 cooperated with Src to induce
      activation of Rac1 in vivo and the formation of membrane ruffles. Similarly,
      activation of JNK and the c-jun promoter by Src were also potently increased by
      Tiam1. Together, these results suggest that Vav2 and Tiam1 may act as downstream
      effectors of Src, thereby regulating Rac1-dependent pathways that participate in
      Src-induced cell transformation.

PMID- 12810716
TI  - Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by
      interaction with the immunophilin XAP2.
AB  - The cyclic AMP-specific phosphodiesterase (PDE4) isoform PDE4A5 interacted with
      the immunophilin XAP2 in a yeast two-hybrid assay. The interaction was confirmed
      in biochemical pull-down analyses. The interaction was specific, in that PDE4A5
      did not interact with the closely related immunophilins AIPL1, FKBP51, or FKBP52.
      XAP2 also did not interact with other PDE4A isoforms or typical isoforms from the
      three other PDE4 subfamilies. Functionally, XAP2 reversibly inhibited the
      enzymatic activity of PDE4A5, increased the sensitivity of PDE4A5 to inhibition
      by the prototypical PDE4 inhibitor 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2
      pyrrolidinone (rolipram) and attenuated the ability of cAMP-dependent protein
      kinase to phosphorylate PDE4A5 in intact cells. XAP2 maximally inhibited PDE4A5
      by approximately 60%, with an IC50 of 120 nm, and reduced the IC50 for rolipram
      from 390 nm to 70-90 nm. Co-expression of XAP2 and PDE4A5 in COS7 cells showed
      that they could be co-immunoprecipitated and also reduced both the enzymatic
      activity of PDE4A5 and its IC50 for rolipram. Native XAP2 and PDE4A5 could be co
      immunoprecipitated from the brain. The isolated COOH-terminal half of XAP2 (amino
      acids 170-330), containing its tetratricopeptide repeat domain, but not the
      isolated NH2-terminal half (amino acids 1-169), containing the immunophilin
      homology region, similarly reduced PDE4A5 activity and its IC50 for rolipram.
      Mutation of Arg271 to alanine, in the XAP2 tetratricopeptide repeat region,
      attenuated its ability to both interact with PDE4A5 in two-hybrid assays and to
      inhibit PDE4A5 activity. Either the deletion of a specific portion of the unique
      amino-terminal region or specific mutations in the regulatory UCR2 domain of
      PDE4A5 attenuated its ability be inhibited by XAP2. We suggest that XAP2
      functionally interacts with PDE4A5 in cells.

PMID- 12810718
TI  - Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions
      between DCC and heparin.
AB  - Netrins are secreted proteins that elicit both attractive and repulsive responses
      in migrating cells in the central and peripheral nervous systems. Netrins
      interact with members of two distinct families of transmembrane receptors,
      represented by DCC (deleted in colorectal cancer) and UNC5. A human netrin
      fragment (soluble netrin; sNetrin) was purified from an engineered Chinese
      hamster ovary cell line and used in a pull-down assay to map the interactions
      between netrin and its receptors. We find that sNetrin binds exclusively to the
      fifth fibronectin type III repeat of DCC and to each immunoglobulin repeat of
      UNC5. Both DCC and UNC5 bind to sNetrin with 1:1 stoichiometry in solution, and
      the minimal receptor fragments behave similarly to larger fragments in cross
      linking experiments with purified sNetrin. We find no evidence for formation of a
      ternary complex between sNetrin and soluble forms of DCC and UNC5. We also find
      no evidence for an interaction between DCC and heparin and instead demonstrate
      that a loop on the fifth fibronectin type III repeat of DCC previously implicated
      in mediating interactions with heparin is important for sNetrin binding. Since
      netrin binds heparin, our results suggest that interactions between DCC and
      heparin are probably mediated by netrin.

PMID- 12810719
TI  - A regulatory role for p38 delta MAPK in keratinocyte differentiation. Evidence
      for p38 delta-ERK1/2 complex formation.
AB  - p38 MAPK isoforms are important in the regulation of a variety of cellular
      processes. Among the four described p38 isoforms, p38 alpha, beta, and delta are
      expressed in keratinocytes (Dashti, S. R., Efimova, T., and Eckert, R. L. (2001)
      J. Biol. Chem. 276, 8059-8063). However, very little is known about how
      individual p38 isoforms regulate keratinocyte function. In the present study, we
      use okadaic acid (OA) as a tool to study the role of p38 MAPKs as regulators of
      keratinocyte differentiation. We demonstrate that OA activates p38 delta but not
      other p38 isoforms. p38 delta activation is increased as early as 0.5 h after OA
      addition, and activity is maximal at 8 and 24 h. ERK1 and ERK2 activity are
      reduced on an identical time course. We show that p38 delta forms a complex with
      ERK1/2, and overexpression of p38 delta inhibits ERK1/2 activity without reducing
      ERK1/2 level. Thus, p38 delta may directly suppress ERK1/2 activity. Additional
      studies show that p38 delta is expressed in the epidermis, suggesting a role for
      p38 delta in regulating differentiation. To evaluate its function, we show that
      increased p38 delta activity is associated with increased levels of AP1 and CAATT
      enhancer binding protein factors, increased binding of these factors to the
      involucrin (hINV) promoter, and increased expression. Moreover, these responses
      are maintained in the presence of SB203580, an agent that inhibits p38 alpha and
      beta, further suggesting a central role for the p38 delta isoform. Dominant
      negative p38 also inhibits these responses. These unique observations suggest
      that p38 delta is the major p38 isoform driving suprabasal hINV gene expression
      and that p38 delta directly regulates ERK1/2 activity via formation of a p38
      delta-ERK1/2 complex.

PMID- 12810720
TI  - Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene
      expression.
AB  - Glucocorticoids are secreted from the adrenal glands and act as a peripheral
      effector of the hypothalamic-pituitary-adrenal axis, playing an essential role in
      stress response and homeostatic regulation. In target cells, however, it remains
      unknown how glucocorticoids fine-tune the cellular pathways mediating tissue and
      systemic adaptation. Recently, considerable evidence indicates that adaptation to
      hypoxic environments is influenced by glucocorticoids and there is cross-talk
      between hypoxia-dependent signals and glucocorticoid-mediated regulation of gene
      expression. We therefore investigated the interaction between these important
      stress-responsive pathways, focusing on the glucocorticoid receptor (GR) and
      hypoxia-inducible transcription factor HIF-1. Here we show that, under hypoxic
      conditions, HIF-1-dependent gene expression is further up-regulated by
      glucocorticoids via the GR. This up-regulation cannot be substituted by the other
      steroid receptors and is suggested to result from the interaction between the GR
      and the transactivation domain of HIF-1 alpha. Moreover, our results also
      indicate that the ligand binding domain of the GR is essential for this
      interaction, and the critical requirement for GR agonists suggests the importance
      of the ligand-mediated conformational change of the GR. Because these proteins
      are shown to colocalize in the distinct compartments of the nucleus, we suggest
      that these stress-responsive transcription factors have intimate communication in
      close proximity to each other, thereby enabling the fine-tuning of cellular
      responses for adaptation.

PMID- 12810721
TI  - Endogenously produced endothelial lipase enhances binding and cellular processing
      of plasma lipoproteins via heparan sulfate proteoglycan-mediated pathway.
AB  - Endothelial lipase (EL) is a new member of the triglyceride lipase gene family,
      which includes lipoprotein lipase (LpL) and hepatic lipase (HL). Enzymatic
      activity of EL has been studied before. Here we characterized the ability of EL
      to bridge lipoproteins to the cell surface. Expression of EL in wild-type Chinese
      hamster ovary (CHO)-K1 but not in heparan sulfate proteoglycan (HSPG)-deficient
      CHO-677 cells resulted in 3-4.4-fold increases of 125I-low density lipoprotein
      (LDL) and 125I-high density lipoprotein 3 binding (HDL3). Inhibition of
      proteoglycan sulfation by sodium chlorate or incubation of cells with labeled
      lipoproteins in the presence of heparin (100 microg/ml) abolished bridging
      effects of EL. An enzymatically inactive EL, EL-S149A, was equally effective in
      facilitating lipoprotein bridging as native EL. Processing of LDL and HDL
      differed notably after initial binding via EL to the cell surface. More than 90%
      of the surface-bound 125I-LDL was destined for internalization and degradation,
      whereas about 70% of the surface-bound 125I-HDL3 was released back into the
      medium. These differences were significantly attenuated after HDL clustering was
      promoted using antibody against apolipoprotein A-I. At equal protein
      concentration of added lipoproteins the ratio of HDL3 to VLDL bridging via EL was
      0.092 compared with 0.174 via HL and 0.002 via LpL. In summary, EL mediates
      binding and uptake of plasma lipoproteins via a process that is independent of
      its enzymatic activity, requires cellular heparan sulfate proteoglycans, and is
      regulated by ligand clustering.

PMID- 12810722
TI  - A SOX9 defect of calmodulin-dependent nuclear import in campomelic
      dysplasia/autosomal sex reversal.
AB  - During mammalian sex determination, SOX9 is translocated into the nuclei of
      Sertoli cells within the developing XY gonad. The N-terminal nuclear localization
      signal (NLS) is contained within a SOX consensus calmodulin (CaM) binding region,
      thereby implicating CaM in nuclear import of SOX9. By fluorescence spectroscopy
      and glutaraldehyde cross-linking, we show that the SOX9 HMG domain and CaM
      interact in vitro. The formation of a SOX9.CaM binary complex is calcium
      dependent and is accompanied by a conformational change in SOX9. A CaM
      antagonist, calmidazolium chloride (CDZ), was observed to block CaM recognition
      of SOX9 in vitro and inhibit both nuclear import and consequent transcriptional
      activity of SOX9 in treated cells. The significance of the SOX9-CaM interaction
      was highlighted by analysis of a missense SOX9 mutation, A158T, identified from a
      XY female with campomelic dysplasia/autosomal sex reversal (CD/SRA). This mutant
      binds importin beta normally despite defective nuclear import. Fluorescence and
      quenching studies indicate that in the unbound state, the A158T mutant shows a
      similar conformation to that of the WT SOX9, but in the presence of CaM, the
      mutant undergoes unusual conformational changes. Furthermore, SOX9-mediated
      transcriptional activation by cells expressing the A158T mutant is more sensitive
      to CDZ than cells expressing WT SOX9. These results suggest first that CaM is
      involved in the nuclear transport of SOX9 in a process likely to involve direct
      interaction and second, that CD/SRA can arise, at least in part, from a defect in
      CaM recognition, ultimately leading to reduced ability of SOX9 to activate
      transcription of cartilage and testes-forming genes.

PMID- 12810723
TI  - Identification and characterization of two splice variants of human
      diacylglycerol kinase eta.
AB  - Diacylglycerol kinase (DGK) participates in regulating the intracellular
      concentrations of two bioactive lipids, diacylglycerol and phosphatidic acid. DGK
      eta (eta 1, 128 kDa) is a type II isozyme containing a pleckstrin homology domain
      at the amino terminus. Here we identified another DGK eta isoform (eta 2, 135
      kDa) that shared the same sequence with DGK eta 1 except for a sterile alpha
      motif (SAM) domain added at the carboxyl terminus. The DGK eta 1 mRNA was
      ubiquitously distributed in various tissues, whereas the DGK eta 2 mRNA was
      detected only in testis, kidney, and colon. The expression of DGK eta 2 was
      suppressed by glucocorticoid in contrast to the marked induction of DGK eta 1.
      DGK eta 2 was shown to form through its SAM domain homo-oligomers as well as
      hetero-oligomers with other SAM-containing DGKs (delta 1 and delta 2).
      Interestingly, DGK eta 1 and DGK eta 2 were rapidly translocated from the
      cytoplasm to endosomes in response to stress stimuli. In this case, DGK eta 1 was
      rapidly relocated back to the cytoplasm upon removal of stress stimuli, whereas
      DGK eta 2 exhibited sustained endosomal association. The experiments using DGK
      eta mutants suggested that the oligomerization of DGK eta 2 mediated by its SAM
      domain was largely responsible for its sustained endosomal localization.
      Similarly, the oligomerization of DGK eta 2 was suggested to result in negative
      regulation of its catalytic activity. Taken together, alternative splicing of the
      human DGK eta gene generates at least two isoforms with distinct biochemical and
      cell biological properties responding to different cellular metabolic
      requirements.

PMID- 12810724
TI  - The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and
      degradation.
AB  - The p53 protein is kept labile under normal conditions. This regulation is
      governed largely by its major negative regulator, Mdm2. In response to stress
      however, p53 accumulates and becomes activated. For this to occur, the inhibitory
      effects of Mdm2 have to be neutralized. Here we investigated the role of the
      promyelocytic leukemia protein (PML) in the activation of p53 in response to
      stress. We found that PML is critical for the accumulation of p53 in response to
      DNA damage under physiological conditions. PML protects p53 from Mdm2-mediated
      ubiquitination and degradation, and from inhibition of apoptosis. PML neutralizes
      the inhibitory effects of Mdm2 by prolonging the stress-induced phosphorylation
      of p53 on serine 20, a site of the checkpoint kinase 2 (Chk2). PML recruits Chk2
      and p53 into the PML nuclear bodies and enhances p53/Chk2 interaction. Our
      results provide a novel mechanistic explanation for the cooperation between PML
      and p53 in response to DNA damage.

PMID- 12810725
TI  - 14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac. Platelet
      glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3
      zeta.
AB  - Integrin-induced cytoskeletal reorganizations are initiated by Cdc42 and Rac1 but
      little is known about mechanisms by which integrins activate these Rho GTPases.
      14-3-3 proteins are adaptors implicated in binding and regulating the function
      and subcellular location of numerous signaling molecules. In platelets, the 14-3
      3 zeta isoform interacts with the glycoprotein (GP) Ibalpha subunit of the
      adhesion receptor GP Ib-IX. In this study, we show that integrin-induced
      activation of Cdc42, activation of Rac, cytoskeletal reorganizations, and cell
      spreading were inhibited in Chinese hamster ovary cells expressing full-length GP
      Ibalpha compared with GP Ibalpha lacking the 14-3-3 zeta binding site. Activation
      of Rho GTPases and cytoskeletal reorganizations were restored by expression of 14
      3-3 zeta. Spreading in cells expressing truncated GP Ibalpha was inhibited by co
      expressing a chimeric receptor containing interleukin 2 receptor alpha and GP
      Ibalpha cytoplasmic domain. These results identify a previously unrecognized
      function of 14-3-3 zeta, that of mediating integrin-induced signaling. They show
      that 14-3-3 zeta mediates Cdc42 and Rac activation. They also reveal a novel
      function of platelet GP Ib-IX, that of regulating integrin-induced cytoskeletal
      reorganizations by sequestering 14-3-3 zeta. Signaling across integrins initiates
      changes in cell behavior such as spreading, migration, differentiation,
      apoptosis, or cell division. Thus, introduction of the 14-3-3 zeta binding domain
      of GP Ibalpha into target cells might provide a method for regulating integrin
      induced pathways in a variety of pathological conditions.

PMID- 12810726
TI  - Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic beta
      cells.
AB  - We show that the mitogen-activated protein kinases ERK1/2 are components of the
      mechanism by which glucose stimulates insulin gene expression. ERK1/2 activity is
      required for glucose-dependent transcription from both the full-length rat
      insulin I promoter and the glucose-sensitive isolated E2A3/4 promoter element in
      intact islets and beta cell lines. Dominant negative ERK2 and MEK inhibitors
      suppress glucose stimulation of the rat insulin I promoter and the E2A3/4
      element. Overexpression of ERK2 is sufficient to stimulate transcription from the
      E2A3/4 element. The glucose-induced response is dependent upon ERK1/2
      phosphorylation of a subset of transcription factors that include Beta2 (also
      known as NeuroD1) and PDX-1. Phosphorylation increases their functional activity
      and results in a cumulative transactivation of the promoter. Thus, ERK1/2 act at
      multiple points to transduce a glucose signal to insulin gene transcription.

PMID- 12810727
TI  - The human bile acid-CoA:amino acid N-acyltransferase functions in the conjugation
      of fatty acids to glycine.
AB  - Bile acid-CoA:amino acid N-acyltransferase (BACAT) catalyzes the conjugation of
      bile acids to glycine and taurine for excretion into bile. By use of site
      directed mutagenesis and sequence comparisons, we have identified Cys-235, Asp
      328, and His-362 as constituting a catalytic triad in human BACAT (hBACAT) and
      identifying BACAT as a member of the type I acyl-CoA thioesterase gene family. We
      therefore hypothesized that hBACAT may also hydrolyze fatty acyl-CoAs and/or
      conjugate fatty acids to glycine. We show here that recombinant hBACAT also can
      hydrolyze long- and very long-chain saturated acyl-CoAs (mainly C16:0-C26:0) and
      by mass spectrometry verified that hBACAT also conjugates fatty acids to glycine.
      Tissue expression studies showed strong expression of BACAT in liver,
      gallbladder, and the proximal and distal intestine. However, BACAT is also
      expressed in a variety of tissues unrelated to bile acid formation and transport,
      suggesting important functions also in the regulation of intracellular levels of
      very long-chain fatty acids. Green fluorescent protein localization experiments
      in human skin fibroblasts showed that the hBACAT enzyme is mainly cytosolic.
      Therefore, the cytosolic BACAT enzyme may play important roles in protection
      against toxicity by accumulation of unconjugated bile acids and non-esterified
      very long-chain fatty acids.

PMID- 12810728
TI  - Membrane-anchored CD40 is processed by the tumor necrosis factor-alpha-converting
      enzyme. Implications for CD40 signaling.
AB  - The soluble form of CD40 (sCD40), which co-exists with the membrane-anchored form
      (mCD40), is a natural antagonist of mCD40/CD154 interaction. However, the
      mechanism leading to the production of sCD40 has never been investigated. Here,
      we show that the engagement of mCD40 on the surface of B lymphocytes by anti-CD40
      antibody led to enhanced sCD40 release associated with decreased amounts of
      mCD40. This sCD40 production was not affected by vesicular traffic inhibitors but
      was completely blocked by a broad-spectrum synthetic metalloproteinase (MP)
      inhibitor (GM6001) or a membrane-anchored MP-specific inhibitor (dec-RVKR-cmk).
      Recombinant MP disintegrin tumor necrosis factor-alpha converting enzyme (TACE)
      cleaved the purified CD40 ectodomain/Fc chimeric protein in vitro, giving rise to
      an sCD40 form similar to that shed from B cell cultures. Moreover, spontaneous
      production of sCD40 by mCD40-transfected human embryonic kidney cells
      (constitutively expressing TACE) was enhanced by the overexpression of TACE and
      abrogated by co-transfection with a dominant-negative TACE mutant. These results
      provide strong evidence that sCD40 production is an active process regulated by
      the engagement of mCD40 and its proteolytic cleavage by TACE or a related MP
      disintegrin. Given the antagonistic activity of sCD40 on the CD40/CD154
      interaction, this shedding mechanism might represent an important negative
      feedback control of CD40 functions.

PMID- 12810729
TI  - Mutational, structural, and kinetic studies of the ATP-binding site of
      Methanobacterium thermoautotrophicum nicotinamide mononucleotide
      adenylyltransferase.
AB  - Several residues lining the ATP-binding site of Methanobacterium
      thermoautotrophicum nicotinamide mononucleotide adenylyltransferase (NMNATase)
      were mutated in an effort to better characterize their roles in substrate binding
      and catalysis. Residues selected were Arg-11 and Arg-136, both of which had
      previously been implicated as substrate binding residues, as well as His-16 and
      His-19, part of the HXGH active site motif and postulated to be of importance in
      catalysis. Kinetic studies revealed that both Arg-11 and Arg-136 contributed to
      the binding of the substrate, ATP. When these amino acids were replaced by
      lysines, the apparent Km values of the respective mutants for ATP decreased by
      factors of 1.3 and 2.9 and by factors of 1.9 and 8.8 when the same residues were
      changed to alanines. All four Arg mutants displayed unaltered Km values for NMN.
      The apparent kcat values of the R11K and R136K mutants were the same as those of
      WT NMNATase but the apparent kcat values of the alanine mutants had decreased.
      Crystal structures of the Arg mutants revealed NAD+ and SO42- molecules trapped
      at their active sites. The binding interactions of NAD+ were unchanged but the
      binding of SO42- was altered in these mutants compared with wild type. The
      alanine mutants at positions His-16 and His-19 retained approximately 6 and 1.3%,
      respectively, of WT NMNATase activity indicating that His-19 is a key catalytic
      group. Surprisingly, this H19A mutant displayed a novel and distinct mode of NAD+
      binding when co-crystallized in the presence of NAD+ and SO42-.

PMID- 12810731
TI  - Can we afford to exercise, given current injury rates?

PMID- 12810732
TI  - Sports and recreational injury: the hidden cost of a healthy lifestyle.

PMID- 12810733
TI  - Searching the medical literature.

PMID- 12810734
TI  - Review of evaluations of educational approaches to promote safe storage of
      firearms.
AB  - OBJECTIVE: To systematically review evaluation studies of educational
      interventions promoting safe firearm storage. METHODS: Medline, ERIC, PsycINFO,
      Criminal Justice Periodicals Index, Cumulative Index of Nursing and Allied Health
      Literature, and Sociofile were searched. The references from each potentially
      eligible study were checked, and experts in the field were contacted for
      additional reports. In addition, an internet search was performed to identify
      programs not published in the conventional literature. Sources relevant to safe
      firearm storage promotion were selected and evaluated. RESULTS: Seven studies met
      inclusion criteria: adult subjects, program description was included, and firearm
      storage outcomes were measured. One was a randomized controlled trial and the
      other six were one group pre-test and/or post-test. The studies were classified
      into the following categories based on the intervention strategies used: (1).
      counseling and firearm safety materials (n=3); (2). counseling/educational
      message (n=3); and (3). firearm safety materials distribution (n=1). The outcomes
      were safe firearms storage (firearms locked up and unloaded or removal from home)
      after intervention. Four studies, three using counseling and materials
      distribution, reported improved storage after the interventions. CONCLUSIONS: It
      is not yet clear what types of interventions, or which specific intervention
      components, prompt gun owners to securely store their weapons. Increased
      understanding of gun storage behaviors and stronger evaluation designs will aid
      further understanding of this important issue.

PMID- 12810735
TI  - Evaluation of Safe Kids Week 2001: prevention of scald and burn injuries in young
      children.
AB  - OBJECTIVE: To evaluate Safe Kids Week 2001-a national public awareness campaign
      on scald and burn prevention-run by Safe Kids Canada. DESIGN: Random digit dial
      telephone survey. SETTING: Canada. SUBJECTS: Parents or guardians of children
      under 9 years. Two groups of parents were compared, those "exposed" to the
      campaign (defined as having "seen, heard, or read anything about scald and burn
      prevention during the period 28 May to 3 June 2001") and those "unexposed" to the
      campaign. INTERVENTION: Burn safety information was disseminated via the media,
      5000 retail stores, and 348 community partners across Canada. The campaign
      emphasized four key messages: (1). Lower your water temperature, hot tap water
      could burn your child! (2). Make sure your child is safe in the kitchen. (3).
      Keep hot drinks away from your child. (4). Check your smoke alarms regularly.
      OUTCOME MEASURES: Change in parental knowledge and behavior. RESULTS: A total of
      29871 telephone numbers were called, with a household refusal rate of 27%.
      Nationally, 14% of parents were exposed to the campaign and 504 parents were
      interviewed, 251 in the "exposed" group and 253 in the "unexposed" group. Parents
      exposed to Safe Kids Week 2001 were 1.5-5 times more likely to be aware of key
      campaign messages, and 2-3 times more likely to test and lower the water heater
      temperature, compared with unexposed parents. CONCLUSION: Safe Kids Week 2001
      reached a significant proportion of parents of young children. In addition, the
      campaign appeared to increase burn safety knowledge and lead to behavior changes
      among exposed parents, compared with unexposed parents.

PMID- 12810737
TI  - Productivity losses from injury in China.
AB  - OBJECTIVE: To examine the productivity losses and costs of injury and disease in
      China using an improved approach. METHODS: Potentially productive years of life
      lost (PPYLL) were calculated for injury and four major disease groups
      (respiratory, cardiovascular, infectious, neoplastic). DATA SOURCES: The
      mortality data are from the 1999 National Health Statistics Report and the
      morbidity data from the 1998 Second National Health Service Survey Report.
      RESULTS: Injuries caused an annual PPYLL of 12.6 million years, more than for any
      disease group. The estimated annual economic cost of injury is equivalent to US
      dollars 12.5 billion, almost four times the total public health services budget
      of China. Motor vehicle fatalities accounted for 25% of the total PPYLL from all
      injury deaths. CONCLUSION: Injury control and prevention programs merit priority
      to reflect the social and economic burden of injury in China.

PMID- 12810736
TI  - Sports and recreation related injury episodes in the US population, 1997-99.
AB  - OBJECTIVE: To characterize sports and recreation related (SR) injury episodes in
      the US population. SR activities are growing in popularity suggesting the need
      for increased awareness of SR injuries as a public health concern for physically
      active persons of all ages in the US population. SETTING: The National Health
      Interview Survey (NHIS) is a face-to-face household survey conducted yearly by
      the National Center for Health Statistics, part of the Centers for Disease
      Control and Prevention. Demographic and health data are collected from a
      nationally representative sample of the civilian, non-institutionalized
      population residing in the US. METHODS: Medically attended injury events reported
      in the 1997-99 Injury Section of the NHIS were categorized according to the
      associated sport or recreational activity using a classification scheme based on
      the International Classification of External Causes of Injury system. Episodes
      where the injured person received any type of medical attention (that is, medical
      advice or treatment) from any health care provider were used to report the
      incidence, severity, and nature of SR injuries sustained by US citizens. RESULTS:
      Annually, an estimated seven million Americans received medical attention for SR
      injuries (25.9 injury episodes per 1000 population). For 5-24 year olds, this
      national estimate was about 42% higher than estimates based on SR injuries seen
      only in emergency departments over a similar time frame. The highest average
      annual SR injury episode rates were for children ages 5-14 years (59.3 per 1000
      persons) and persons aged 15-24 years (56.4 per 1000 persons). The SR injury
      episode rate for males was more than twice the rate for females. The age adjusted
      injury rate for whites was 1.5 times higher than for blacks (28.8 v 19.0 per 1000
      population). Basketball was the most frequently mentioned SR activity when the
      injury episode occurred, with a rate of about four injury events per 1000
      population. Strains and sprains accounted for 31% of injury episodes. An
      estimated 1.1 million SR episode related injuries involve the head or neck
      region, of which 17% were internal head injuries. The most common mechanisms of
      injury were struck by/against (34%), fall (28%), and overexertion (13%).
      CONCLUSION: As physical activity continues to be promoted as part of a healthy
      lifestyle, SR injuries are becoming an important public health concern for both
      children and adults. Prevention efforts aimed at reducing SR injuries through
      targeting high risk activities, places of occurrence, activity, risk behaviors,
      and use of protective devices need to go beyond focusing on children and also
      consider physically active adults.

PMID- 12810738
TI  - Risk compensation theory and voluntary helmet use by cyclists in Spain.
AB  - OBJECTIVE: To obtain empirical data that might support or refute the existence of
      a risk compensation mechanism in connection with voluntary helmet use by Spanish
      cyclists. DESIGN: A retrospective case series. SETTING: Spain, from 1990 to 1999.
      SUBJECTS: All 22 814 cyclists involved in traffic crashes with victims, recorded
      in the Spanish Register of Traffic Crashes with Victims, for whom information
      regarding helmet use was available. MAIN OUTCOME MEASURES: Crude and adjusted
      odds ratios for the relation between committing a traffic violation and using a
      helmet. RESULTS: Fifty four percent of the cyclists committed a traffic violation
      other than a speeding infraction. Committing a traffic violation was associated
      with a lower frequency of helmet use (adjusted odds ratio (aOR) 0.63, 95%
      confidence interval (CI) 0.58 to 0.69). Cycling at excessive or dangerous speed,
      a violation observed in 4.5% of the sample, was not significantly associated with
      helmet use either alone (aOR 0.95, 95% CI 0.56 to 1.61) or in combination with
      any other violation (aOR 0.97, 95% CI 0.79 to 1.20). CONCLUSIONS: The results
      suggest that the subgroup of cyclists with a higher risk of suffering a traffic
      crash are also those in which the health consequences of the crash will probably
      be higher. Although the findings do not support the existence of a strong risk
      compensation mechanism among helmeted cyclists, this possibility cannot be ruled
      out.

PMID- 12810739
TI  - Observational study of the extent of driving while suspended for alcohol impaired
      driving.
AB  - OBJECTIVE: To determine the proportion of first time driving while alcohol
      impaired (DWI) offenders who drive while their driver's license is suspended.
      DESIGN: Systematic, unobtrusive observations were conducted by surveillance
      professionals from Pinkerton Investigative Services, Inc, of first time offenders
      in the City of Milwaukee, Wisconsin, and Bergen County, New Jersey. Observations
      included two four hour periods during suspension (one weekday morning, one
      Friday/Saturday evening) and two four hour periods after license reinstatement
      (matched by day of week and time of day). Focus groups of first time offenders
      were conducted in each site. SETTING: New Jersey laws pertaining to license
      suspension for DWI and driving while suspended are stronger than Wisconsin laws.
      SUBJECTS: 93 recently convicted first time DWI offenders (57 in Milwaukee and 36
      in Bergen County). MAIN OUTCOME MEASURES: Proportion of subjects observed driving
      during suspension and after license reinstatement, with reference to all subjects
      and subjects observed traveling by any means. RESULTS: Of subjects observed
      traveling while suspended, 88% of Milwaukee subjects compared with 36% of Bergen
      County subjects drove. Five percent of Milwaukee subjects and 78% of Bergen
      County subjects reinstated their driver's license. Bergen County subjects were
      significantly more likely to drive after reinstatement (54%) than during
      suspension (25%). CONCLUSION: Prevalence of driving while suspended among first
      time offenders is high and can vary substantially between jurisdictions. However,
      the license suspension can have a positive impact on the driving patterns of
      offenders during suspension, relative to after license reinstatement. Lower
      prevalence of driving while suspended in New Jersey may partly be attributable to
      that state's tougher laws.

PMID- 12810740
TI  - A randomised trial of hip protector use by frail older women living in their own
      homes.
AB  - OBJECTIVES: To investigate the efficacy and effectiveness of hip protectors in
      frail community living older women. DESIGN: Randomised controlled trial. SETTING:
      Aged care health services in New South Wales, Australia. PATIENTS: 600 women 74
      years of age or more (mean age 83 years), who had two or more falls or one fall
      requiring hospital admission in the previous year, and who lived in their own
      homes. INTERVENTION: Use of hip protectors. MAIN OUTCOME MEASURES: Adherence with
      use of hip protectors, falls, incidence of hip fracture, and adverse effects of
      use of hip protectors. RESULTS: Adherence was approximately 53% over the duration
      of the study and hip protectors were worn at the time of 51% of falls in the
      intervention group. The risk of hip fracture when falling while wearing hip
      protectors, compared with a fall with no hip protectors in place, was
      significantly reduced (relative risk (RR) 0.23, 95% confidence interval (CI) 0.08
      to 0.67). On an intention to treat analysis, 21 and 22 hip fractures occurred in
      the intervention and control groups respectively (adjusted RR 0.92, 95% CI 0.51
      to 1.68). Three users of hip protectors sustained a hip fracture while wearing
      properly applied protectors, while 16 hip protector users (5%) developed minor
      local complications. CONCLUSIONS: Hip protectors prevent hip fractures in
      community dwelling older women if worn at the time of a fall. The overall
      effectiveness of hip protectors was not established in this study, because of
      incomplete adherence with use of the protectors, and limited statistical power.

PMID- 12810741
TI  - Persistence of effects of a brief intervention on parental restrictions of teen
      driving privileges.
AB  - OBJECTIVE: The purpose of this study was to determine the extent to which effects
      of exposure to a brief intervention designed to increase parental restrictions on
      teen driving privileges persisted over time. DESIGN: A total of 658 parents and
      their 16 year old adolescents were recruited from a local motor vehicle
      administration (MVA) site as adolescents successfully tested for provisional
      licenses. At the MVA, parents completed written surveys about expected teen
      driving during the first month of provisional licensure. Afterwards, on weeks
      assigned as intervention, parents watched a video and were given the video and a
      driving agreement to take home. Both parents and teens completed follow up
      telephone interviews about communication, amounts, and limits on teen driving at
      one month (579 dyads), four months (529 dyads), and nine months (528 dyads).
      RESULTS: The results indicated that both intervention parents and teens were much
      more likely to report using a driving agreement at each follow up during the nine
      month period. Significant treatment group differences persisted for communication
      about driving, but effects related to limits on teen driving that were evident at
      one month declined over time. Reports for passenger, road, and overall limits
      remained significant at four months; fewer were present at nine months. There
      were no differences in amounts of teen driving at four or nine months.
      CONCLUSIONS: It is possible to reach parents through brief interventions at the
      MVA and successfully promote increases in initial parental restrictions on teen
      driving with modest persistence for at least four months.

PMID- 12810742
TI  - Buying a handgun for someone else: firearm dealer willingness to sell.
AB  - OBJECTIVE: To examine firearm dealer willingness to sell when a handgun is being
      purchased for another person. US law requires a background check of the purchaser
      but not the end user of a firearm. SUBJECTS AND METHODS: A total of 120 handgun
      dealers (six from each of the 20 largest US cities with 10 or more dealers)
      participated in telephone interviews. Dealers within each city were randomly
      assigned to a male or female interviewer and then randomly assigned to one of
      three purchase conditions-when the consumer said that the handgun was for
      him/herself, a gift for a girl/boyfriend, or for a girl/boyfriend "because s/he
      needs it". RESULTS: Most dealers were willing to sell a handgun regardless of the
      end user (self: 87.5%; gift: 70.8%; "need": 52.5%). Multivariate analyses
      indicate that dealers in the Midwest, South, and West were more willing to sell
      than those in the Northeast (adjusted odds ratio (AOR) = 21.30, 18.74, and 8.93,
      respectively) and that willingness to sell is lower when the sale would be
      illegal, that is, under the "need" condition (AOR = 0.20). CONCLUSIONS: and
      implications: Dealers are in a position to exercise judgment when a customer is
      explicit about buying a firearm for someone else. Some appeared willing to ignore
      or sidestep relevant information even when told that the end user was prohibited
      from purchasing a firearm him/herself. In the absence of federal handgun
      registration, which would track ownership changes, resources with which to
      conduct compliance checks (for example, as are conducted to identify retailers
      who sell tobacco or alcohol to under-age persons) seem warranted.

PMID- 12810743
TI  - Impact of handgun types on gun assault outcomes: a comparison of gun assaults
      involving semiautomatic pistols and revolvers.
AB  - OBJECTIVE: To examine whether gun assaults committed with semiautomatic pistols
      are more injurious and lethal than those committed with revolvers. SETTING:
      Jersey City, New Jersey from 1992 through 1996. METHODS: Using police records on
      fatal and non-fatal handgun assaults, t tests and chi(2) tests were employed to
      determine if attacks with pistols result in more shots fired than those with
      revolvers, leading to more gunshot victims and more severely wounded victims.
      RESULTS: More shots were fired in attacks with pistols (average = 3.2 to 3.7)
      than in attacks with revolvers (average = 2.3 to 2.6). Although pistol use was
      unrelated to the probability that an incident resulted in any injury or death, it
      was associated with a 15% increase in the number of wounded victims in those
      cases in which people were shot (1.15 per pistol case, 1.0 per revolver case),
      implying that the total number of gunshot victims may have been 9.4% lower had
      pistols not been used in any attacks. Pistol use was not related to the number of
      wounds per gunshot victim. CONCLUSIONS: The findings provide limited evidence
      that recent growth in the production and use of pistols has contributed to higher
      levels of gunshot victimizations. However, available data did not permit an
      assessment of whether the associations between gun types and assault outcomes are
      mediated by characteristics of incidents and actors.

PMID- 12810744
TI  - A new approach to the analysis of multiple injuries using data from a national
      trauma registry.
AB  - OBJECTIVE: To present a new systematic approach for summarizing multiple injury
      diagnosis data into patient injury profiles. DESIGN: International Classification
      of Diseases, ninth revision, clinical modification injury diagnosis codes were
      classified using a modification of the Barell body region by nature of injury
      diagnosis matrix, then grouped by body region, injury nature, or a combination of
      both. Profiles were built which describe patients' injury combinations based on
      matrix units, enabling the analysis of patients, and not only the study of
      injuries. SETTING: The Israeli national trauma registry was used to retrieve
      patient demographic data, injury details, and information on treatment and
      outcome. Patients or subjects: All hospitalized patients injured in road traffic
      accidents and included in the trauma registry from January 1997 to December 2000
      were included. MAIN OUTCOME MEASURES: Patient profiles consisting of body
      regions, injury natures, their combination, and their clinical outcomes. RESULTS:
      The study population comprised 17459 patients. Head and neck injuries were the
      most frequent in all subpopulations except for motorcyclists who sustained most
      injuries in the extremities. Fractures were the most common injury nature (60%).
      Pedestrians and drivers had the highest proportion of multiple injuries in both
      profiles. Forty eight percent of the patients had a single cell profile. The most
      frequent conditions as a sole condition were extremity fractures (14%), internal
      injuries to the head (11%), and injuries of other nature to the torso (6%).
      Mortality, length of stay, and intensive care unit treatment varied dramatically
      between profiles and increased for multiple injury profiles. Inpatient death was
      an outcome for 3.3% overall; however, in patients with an internal injury to the
      head and torso, inpatient death rate was nine times higher, at 31%. CONCLUSIONS:
      Profiles maintain information on body region and nature of injury. The use of
      injury profiles in describing the injured improves the understanding of casemix
      and can be useful for efficient staffing in multidisciplinary trauma teams and
      for various comparisons.

PMID- 12810745
TI  - Characteristics of drowning by different age groups.
AB  - CONTEXT: While it is known that the risk of unintentional drowning varies with
      age, the manner in which drowning episode characteristics vary by age has not
      been well described. Such information might be useful for prevention. OBJECTIVE:
      To describe characteristics of drowning by age group. DESIGN: Retrospective
      review of the characteristics of drowning victims and their drowning incidents
      obtained from death certificates, medical examiner, pre-hospital, emergency
      department, and hospital records. SETTING: Three counties in Western Washington
      state. SUBJECTS: Residents who died (n=709) of unintentional drowning within the
      study region during 1980 through 1995. OUTCOMES: Age specific counts,
      proportions, and rates per million person years were estimated for and compared
      among six age groups. RESULTS: Rates varied by age group: 0-4 (30.5), 5-14
      (11.6), 15-19 (29.9), 20-34 (21.5), 35-64 (12.5), and 65 years or older (21.2).
      Among those 0-4 years, the proportions that drowned in pools, bathtubs, and open
      water were nearly equal. But from age 5-64 years, over 69% of deaths were in open
      water. Among those 65 years and older, the deaths were almost evenly divided
      between bathtub and open water; bathtub drowning rates were highest in this age
      group, 10.9. Pre-drowning activities were divided into boating, swimming, car
      passenger, bathing, and fell in while doing something else. Most (64/89, 76%)
      victims aged 0-4 years drowned while bathing or after falling in. Among those 15
      19 years, most occurred while swimming (24/79, 34%) or boating (22/79, 31%). The
      drowning event was least often witnessed among those 0-4 years (10/36, 28%), and
      most often witnessed (44/58, 76%) among those 15-19 years. Medical care (pre
      hospital, emergency department, or hospital) was most often involved in drownings
      of those 0-4 years (70/89, 79%) and least among those over 65 years (11/86, 13%).
      CONCLUSION: The characteristics of drowning episodes vary greatly by age.
      Different prevention strategies may be needed for different age groups.

PMID- 12810746
TI  - Car seatbelt use during pregnancy in Japan: determinants and policy implications.
AB  - CONTEXT: Pregnant women are exempted from the current seatbelt legislation in
      Japan despite the fact that seatbelt use is essential to reduce the risk of
      fatalities for these women and their fetuses in car crashes. OBJECTIVE: To
      examine factors that might influence seatbelt use during pregnancy. METHODS: A
      cross sectional study, with data collected via an anonymous, self administered
      questionnaire at obstetric clinics in suburban areas of Japan. Altogether 880
      pregnant women receiving prenatal care in July 2001 were recruited. The relative
      effects of factors that might influence seatbelt use during pregnancy were
      estimated using logistic regression analysis. RESULTS: Almost 70%-80% of pregnant
      women were consistent seatbelt wearers before pregnancy but seatbelt compliance
      was reduced by about half at 20 weeks or more gestation. Only 20% had received
      information on maternal seatbelt use, with one third reporting that seatbelt use
      is beneficial during pregnancy. Those who perceived that maternal seatbelt use is
      beneficial tended to maintain use, but daily car users and those who knew that
      they were exempted from seatbelt legislation were more likely to reduce use.
      CONCLUSIONS: Knowledge of the legislative exemption for pregnant women,
      misunderstanding of the benefits, and daily car use contributed to the reduction
      in seatbelt use after pregnancy.

PMID- 12810747
TI  - Differential ranking of causes of fatal versus non-fatal injuries among US
      children.
AB  - OBJECTIVE: Leading causes of fatal and non-fatal injury among US children aged
      <15 years were compared. METHOD: A descriptive study was conducted using
      nationally representative data on injury related deaths (National Vital
      Statistics System) and on non-fatal injury related emergency department visits
      (IEDV; National Electronic Injury Surveillance System-All Injury Program). Data
      were accessed using a publicly available web based system. RESULTS: Annually, an
      estimated 7100000 pediatric IEDV and 7400 injury deaths occurred. The overall non
      fatal to fatal ratio (NF:F) was 966 IEDV:1 death. Among deaths, the leading
      causes were motor vehicle traffic occupants (n = 1700; NF:F = 150:1),
      suffocations (n = 1037; NF:F = 14:1), and drownings (n = 971, NF:F = 6:1). Among
      non-fatal injuries, falls (estimated 2400000) and struck by/against (estimated
      1800000) were the most common causes, but substantially less lethal (NF:F =
      19000:1 and 15000:1, respectively). CONCLUSIONS: The leading causes of pediatric
      fatal and non-fatal injuries differed substantially. This study indicates the
      need for consideration of common causes of non-fatal injury, especially falls.

PMID- 12810748
TI  - Children's bicycle helmet use and injuries in Hillsborough County, Florida before
      and after helmet legislation.
AB  - The purpose of this research was to explore the changes in children's bicycle
      helmet use and motor vehicle bicycle related injuries in Hillsborough County,
      Florida before and after passage of the Florida's bicycle helmet law for children
      under the age of 16. The results show a significant increase in bicycle helmet
      use among children, ages 5-13, in the post-law years compared with the pre-law
      years. Also, there has been a significant decline in the rates of bicycle related
      motor vehicle injuries among children in the post-law years compared with the pre
      law years. Although there have been complementary educational and outreach
      activities in the county to support helmet use, it appears that the greatest
      increase in use occurred after the passage of the helmet law. It is recommended
      that educational efforts continue to sustain helmet use rates and decreases in
      injuries.

PMID- 12810749
TI  - Validation of a home safety questionnaire used in a randomised controlled trial.
AB  - OBJECTIVE: To measure the validity of self reported safety practices from a
      questionnaire, completed by families participating in a home safety randomised
      controlled trial. METHODS: The postal questionnaire was used to measure secondary
      outcomes in a randomised controlled trial. The answers to 26 questions that could
      be assessed by observation were checked by a home visit. Families were invited to
      take part in a "home safety check"; they were not told that the visit was part of
      a validation study. At the time of the visit the researcher was blind to the self
      reports in the questionnaires. RESULTS: Sixty four questionnaires were validated
      by visits to 64 households. Percentage agreement ranged from 58% to 100%.
      Sensitivity was high (68% or above) for most safety practices. The positive
      predictive value was also high for most safety practices (78% or above for 15 of
      the 16 practices). CONCLUSIONS: This study found a fairly high degree of
      consistency between self reported data and actual observations. The findings from
      this relatively small study need confirmation from larger studies.

PMID- 12810750
TI  - Routine narrative analysis as a screening tool to improve data quality.
AB  - AIM: To determine whether narrative information in emergency department
      surveillance systems can be systematically interrogated to improve our
      understanding of the causes of injury. METHODS: Screening algorithms for
      location, intent, and activity were developed from structured analysis of
      narrative data from 98999 records. The algorithms were then tested on a 50000
      record database containing entries in both of the two narrative fields. A proxy
      gold standard was defined as the total extract using both code and narrative.
      Sensitivity and specificity of the emergency department coding and narrative
      algorithms was calculated. RESULTS: The proportion of records carrying an
      informative emergency department code was higher in records containing narrative
      the percentage of causes coded "not know" dropped by 28.3%. The sensitivity of
      coded data varied from 42% to 98 % and from 33% to 99% for narrative data.
      Narrative analysis increased the percentage of home injuries identified by 19%,
      assaults by 26%, and rugby injuries by 137%. CONCLUSIONS: Using a small amount of
      narrative is a practical and effective means of developing more informative
      injury causation data in an emergency department based surveillance system. It
      allows for internal validation of the codes and for the identification of
      emerging hazards without adding more "tick boxes" or further burdening data entry
      clerks.

PMID- 12810751
TI  - Violent attacks on Middle Easterners in the United States during the month
      following the September 11, 2001 terrorist attacks.
AB  - OBJECTIVES: To document and describe hate related violent attacks on Middle
      Easterners or those perceived to be Middle Easterners during the month following
      the September 11, 2001 terrorist attacks in New York City and Washington, DC.
      METHODS: The LexisNexis database of newspaper reports were used to identify
      incidents of hate related violent acts against Middle Easterners or those
      perceived to be Middle Easterners in the US between September 1 and October 11,
      2001. A total of 100 incidents of hate related violence were identified in the
      2659 news articles that were reviewed. RESULTS: Of the 100 incidents of violent
      victimization that took place during the period September 1 to October 11, only
      one incident occurred before September 11. The 99 incidents that occurred after
      September 11 involved at least 128 victims and 171 perpetrators. Most violent
      victimizations occurred within 10 days of the attacks, involved male perpetrators
      and male victims, and occurred in convenience stores, on the streets, at gas
      stations, at schools/colleges, and at places of worship. DISCUSSION: Most violent
      victimizations occurred in the 10 days immediately following the terrorist
      attacks indicating that interventions that promote tolerance and understanding of
      diversity need to be implemented quickly in order to be effective. In addition,
      patrolling by police and Neighborhood Watch programs around convenience stores
      and gas stations may also be effective strategies for reducing hate related
      violent crimes.

PMID- 12810754
TI  - Is there a side predilection for cerebrovascular disease?
AB  - In studies on carotid artery intima-media thickness and stroke, researchers
      implicitly assume that cerebrovascular abnormalities show a symmetrical
      distribution. To evaluate whether there is a difference in intima-media thickness
      between the 2 carotids, we compared left and right common carotid artery intima
      media thickness as measured by B-mode ultrasonography in a group of 102 untreated
      hypertensive patients. This yielded a significant difference between both sides
      (left, 0.75+/-0.11 mm; right, 0.71+/-0.11 mm; P<0.001). This was associated with
      a higher cross-sectional area of the intima-media complex and a higher flow
      velocity at the left side. Arterial diameters, however, were not different. We
      also assessed whether there is a side preference with respect to cerebrovascular
      accidents. To this end, we explored our population-based Stroke Registry of 1843
      subjects and indeed found a significantly higher incidence of nonlacunar
      cerebrovascular stroke at the left side, whereas lacunar infarcts were
      symmetrically distributed. Our findings suggest a predilection for
      cerebrovascular disease at the left side, which may be related to greater
      hemodynamic stress and intimal damage in the left carotid artery.

PMID- 12810755
TI  - Downregulation of angiotensin subtype 1 receptor in rostral ventrolateral medulla
      during endotoxemia.
AB  - We reported recently that an upregulation of the inducible nitric oxide synthase
      (iNOS) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor
      neurons are located, is a crucial determinant for the elicitation of
      cardiovascular depression during experimental endotoxemia. The current study
      evaluated the hypothesis that a downregulation of the molecular synthesis and
      functional expression of angiotensin subtype 1 receptor (AT1R) in the RVLM is
      consequential to this upregulated iNOS. In adult Sprague-Dawley rats maintained
      under propofol anesthesia, intravenous administration of Escherichia coli
      lipopolysaccharide (15 mg/kg) elicited a reduction, followed by an augmentation
      and a secondary decrease in sympathetic vasomotor outflow, together with
      progressive hypotension and bradycardia. There was also a progressive increase in
      iNOS mRNA and protein level in the ventrolateral medulla. This was followed by a
      significant downregulation of both mRNA and protein levels of AT1R in the
      ventrolateral medulla, alongside reduced efficacy of angiotensin II (50 pmol) to
      induce an increase in systemic arterial pressure, heart rate, or sympathetic
      vasomotor outflow on unilateral microinjection into the RVLM. Pretreatment with
      microinjection of a selective iNOS inhibitor, S-methylisothiourea (250 pmol)
      bilaterally into the RVLM significantly reversed the reduction in both synthesis
      and activity of AT1R. We conclude that a downregulation of molecular synthesis
      and functional expression of AT1R in the ventrolateral medulla is consequential
      to the overproduction of NO through upregulation of iNOS in the RVLM and may
      underlie the cardiovascular depression that takes place during experimental
      endotoxemia.

PMID- 12810756
TI  - Time course of vascular structural changes during and after short-term
      antihypertensive treatment.
AB  - The present study characterized the persistent changes (ie, off-treatment)
      resulting from short-term antihypertensive treatments on mean arterial pressure
      (MAP) and structurally based vascular resistance. Rats were treated for 14 days
      with enalapril (30 mg x kg(-1) x d(-1)) with regular (ENAL, 0.4%) or low salt
      (ELS, 0.04%) diets, or a triple therapy (Triple: hydralazine 45 mg x kg(-1) x d(
      1), hydrochlorothiazide 100 mg/L, and nifedipine 200 mg/d). MAP was continuously
      recorded via radiotelemetry. Structurally based hindlimb vascular resistance
      properties (resistance at maximum dilation [Max Dil]; resistance at maximum
      constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3
      weeks after all drugs were withdrawn. Aortic urokinase plasminogen activator
      (uPA) activity was measured by zymography after 14 days of ELS. All treatments
      induced a significant, persistent decrease in the off-treatment MAP (ENAL
      downward arrow 12+/-4.6%, ELS downward arrow 16+/-2.6%, Triple downward arrow 5+/
      4.17%). During treatment (14 days) the enalapril group had significant changes in
      the index of medial bulk (Max Con downward arrow 15+/-2.6%), but only minimal
      changes in lumen properties (Max Dil downward arrow 3+/-6.5%, NS). After stopping
      therapy, vascular properties at Max Dil were significantly decreased only in the
      2 enalapril groups (ENAL downward arrow 15+/-7.9%, P<0.05; ELS downward arrow 9+/
      6.0%, P<0.05; Triple downward arrow 2+/-9.8%, NS), whereas Max Con was
      significantly decreased in all groups (ENAL downward arrow 12+/-8.0%, ELS
      downward arrow 16+/-6.1%, Triple downward arrow 7+/-5.4%). At 14 days of ELS
      treatment, there was increased aortic uPA activity (1.6-fold). The findings
      reveal that various short-term antihypertensive treatments can produce persistent
      long-term changes in MAP and vascular structure. Further, the magnitude of the
      depressor response may be as important in inducing persistent changes as is the
      removal of angiotensin II.

PMID- 12810757
TI  - Cyclic AMP response element-binding protein mediates reactive oxygen species
      induced c-fos expression.
AB  - Although the cyclic AMP response element-binding protein (CREB) plays an
      important role in the survival of neuronal cells and T lymphocytes, the role of
      CREB in vascular smooth muscle cells (VSMCs) is incompletely characterized. We
      examined the role of CREB in VSMCs stimulated with reactive oxygen species.
      Activation of CREB was examined by Western blot analysis with an antibody that
      specifically recognizes phosphorylation at serine 133 of CREB, which is a
      critical marker of activation. Hydrogen peroxide (H2O2) time-dependently induced
      phosphorylation of CREB, with a peak at 15 minutes. The H2O2-induced
      phosphorylation of CREB was partially blocked by inhibition of either
      extracellular signal-regulated protein kinase kinase by PD98059 or of p38 mitogen
      activated protein kinase (MAPK) by SB203580. AG1478, an epidermal growth factor
      receptor (EGFR) inhibitor, suppressed the H2O2-induced phosphorylation of CREB
      and tyrosine phosphorylation of EGFR. Overexpression of the dominant-negative
      form of CREB by an adenovirus vector suppressed H2O2-induced c-fos expression.
      These findings suggest that H2O2 induces CREB phosphorylation through EGFR
      transactivation and mitogen-activated protein kinase pathways. CREB might be a
      novel redox-sensitive transcription factor involved in the regulation of VSMC
      gene expression.

PMID- 12810758
TI  - Baroreflex control of muscle sympathetic nerve activity after carotid body tumor
      resection.
AB  - Bilateral carotid body tumor resection causes a permanent attenuation of vagal
      baroreflex sensitivity. We retrospectively examined the effects of bilateral
      carotid body tumor resection on the baroreflex control of sympathetic nerve
      traffic. Muscle sympathetic nerve activity was recorded in 5 patients after
      bilateral carotid body tumor resection (1 man and 4 women, 51+/-11 years) and 6
      healthy control subjects (2 men and 4 women, 50+/-7 years). Baroreflex
      sensitivity was calculated from changes in R-R interval and muscle sympathetic
      nerve activity in response to bolus injections of phenylephrine and
      nitroprusside. In addition, sympathetic responses to the Valsalva maneuver and
      cold pressor test were measured. The integrated neurogram of patients and control
      subjects contained a similar pattern of pulse synchronous burst of nerve
      activity. Baroreflex control of both heart rate and sympathetic nerve activity
      were attenuated in patients as compared with control subjects [heart rate
      baroreflex sensitivity: 3.68+/-0.93 versus 11.61+/-4.72 ms/mm Hg (phenylephrine,
      P=0.011) and 2.53+/-1.36 versus 5.82+/-1.94 ms/mm Hg (nitroprusside, P=0.05);
      sympathetic baroreflex sensitivity: 3.70+/-2.90 versus 7.53+/-4.12 activity/100
      beats/mm Hg (phenylephrine, P=0.10) and 3.93+/-4.43 versus 15.27+/-10.03
      activity/100 beats/mm Hg (nitroprusside, P=0.028)]. The Valsalva maneuver
      elicited normal reflex changes in muscle sympathetic nerve activity, whereas
      heart rate responses were blunted in the patients with bilateral carotid body
      tumor resection. Maximal sympathetic responses to the cold pressor test did not
      differ between the two groups. Denervation of carotid sinus baroreceptors as the
      result of bilateral carotid body tumor resection produces chronic impairment of
      baroreflex control of both heart rate and sympathetic nerve activity. During the
      Valsalva maneuver, loss of carotid baroreflex control of heart rate is less well
      compensated for by the extra carotid baroreceptors than the control of muscle
      sympathetic nerve activity.

PMID- 12810759
TI  - Oestrogen, brain function, and neuropsychiatric disorders.

PMID- 12810760
TI  - Clinical radiologic correlations in acute stroke: is the signal intensity at the
      end of the tunnel getting brighter quicker?

PMID- 12810761
TI  - Head injury and Alzheimer's disease.

PMID- 12810762
TI  - Surgery for chronic subdural haematoma: is there an evidence base?

PMID- 12810763
TI  - The outcome of depressive disorders in the setting of neurological illness.

PMID- 12810765
TI  - Long term treatment and disease severity change brain responses to levodopa in
      Parkinson's disease.
AB  - OBJECTIVES: Degeneration of nigrostriatal neurons and subsequent striatal
      dopamine deficiency produce many of the symptoms of Parkinson disease (PD).
      Initially restoration of striatal dopamine with oral levodopa provides
      substantial benefit, but with long term treatment and disease progression,
      levodopa can elicit additional clinical symptoms, reflecting altered effects of
      levodopa in the brain. The authors examined whether long term treatment affects
      the brain's response to levodopa in the absence of these altered clinical
      responses to levodopa. METHODS: Positron emission tomography (PET) measurements
      were used of brain-blood flow before and after an acute dose of levodopa in three
      groups: PD patients treated long term with levodopa without levodopa induced
      dyskinesias, levodopa naive PD patients, and controls. RESULTS: It was found that
      the PD group treated long term responded to acute levodopa differently from
      controls in left sensorimotor and left ventrolateral prefrontal cortex. In both
      regions, the treated PD group had decreased blood flow whereas the control group
      had increased blood flow in response to levodopa. Levodopa naive PD patients had
      little or no response to levodopa in these regions. Within the treated PD group,
      severity of parkinsonism correlated with the degree of abnormality of the
      sensorimotor cortex response, but not with the prefrontal response. CONCLUSIONS:
      It is concluded that long term levodopa treatment and disease severity affect the
      physiology of dopaminergic pathways, producing altered responses to levodopa in
      brain regions associated with motor function.

PMID- 12810766
TI  - Lewy body cortical involvement may not always predict dementia in Parkinson's
      disease.
AB  - BACKGROUND: The presence of Lewy bodies (LB) in the neocortex and limbic system
      in patients with Parkinson's disease (PD) is commonly thought to be linked with
      cognitive impairment. The authors present here a series of patients with
      diagnosis of PD in life and no significant cognitive impairment who, at necropsy,
      satisfied the current neuropathological criteria for dementia with Lewy bodies
      (DLB). METHODS: Two hundred and seventy six brains with PD pathology were
      examined at the Queen Square Brain Bank in London between 1993 and 1999. The
      neuropathological diagnosis was PD, but 117 patients also had sufficient LB
      involvement above the brain stem to satisfy the current neuropathological
      criteria for DLB (50 patients had a neuropathological picture consistent with the
      limbic category of DLB and 67 with neocortical DLB). Forty eight cases were
      excluded who developed early cognitive impairment together with motor features of
      parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with
      coexistent features of advanced Alzheimer's disease changes. Thirty eight
      patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB
      pathology) were found where there was no or very late cognitive impairment
      reported in the clinical records. RESULTS: Selected cases were 24 men and 14
      women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1)
      years and a mean disease duration of 15.3 (5.5) years. At some time during the
      evolution of the disease 21 patients developed different degrees of cognitive
      impairment (after a mean disease duration of 12.2 (4.8) years). Clinical
      diagnosis at death was PD in 10 cases and PD with dementia in 11. In the
      remaining 17 patients no history of cognitive impairment was ever recorded in
      life and all of them had a clinical diagnosis of PD at death; in this subgroup,
      nine patients later revealed a neuropathological picture consistent with limbic
      (or transitional) category of DLB and eight with neocortical DLB. Interestingly,
      in all these patients the parkinsonian features including the response to
      dopaminergic drugs were indistinguishable from classic brain stem PD.
      CONCLUSIONS: The authors demonstrate that the classic pathology of DLB can
      commonly be seen outside the generally accepted clinical spectrum for DLB and
      that important factors other than the absolute number of LB in the neocortex and
      limbic system influence the development of cognitive impairment in PD.
      Furthermore, the pathology of PD may be indistinguishable from that reported in
      DLB, suggesting that the two clinicopathological syndromes may be attributable to
      the same biological abnormality.

PMID- 12810767
TI  - Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a
      partial replication.
AB  - OBJECTIVE: To determine, using a systematic review of case-control studies,
      whether head injury is a significant risk factor for Alzheimer's disease. We
      sought to replicate the findings of the meta-analysis of Mortimer et al (1991).
      METHODS: A predefined inclusion criterion specified case-control studies eligible
      for inclusion. A comprehensive and systematic search of various electronic
      databases, up to August 2001, was undertaken. Two independent reviewers screened
      studies for eligibility. Fifteen case-control studies were identified that met
      the inclusion criteria, of which seven postdated the study of Mortimer et al.
      RESULTS: We partially replicated the results of Mortimer et al. The meta-analysis
      of the seven studies conducted since 1991 did not reach significance. However,
      analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to
      2.06), indicating an excess history of head injury in those with Alzheimer's
      disease. The finding of Mortimer et al that head injury is a risk factor for
      Alzheimer's disease only in males was replicated. The excess risk of head injury
      in those with Alzheimer's disease is only found in males (males: OR 2.29, 95% CI
      1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47). CONCLUSIONS: This study
      provides support for an association between a history of previous head injury and
      the risk of developing Alzheimer's disease.

PMID- 12810768
TI  - Melissa officinalis extract in the treatment of patients with mild to moderate
      Alzheimer's disease: a double blind, randomised, placebo controlled trial.
AB  - OBJECTIVE: To assess the efficacy and safety of Melissa officinalis extract using
      a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's
      disease. DESIGN: A four month, parallel group, placebo controlled trial
      undertaken in three centres in Tehran, Iran. METHODS: Patients with mild to
      moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24
      men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease
      assessment scale (ADAS-cog) and <or= 2 on the clinical dementia rating (CDR) were
      randomised to placebo or fixed dose of Melissa officinalis extract. The main
      efficacy measures were the change in the ADAS-cog and CDR-SB scores compared with
      baseline. Side effects were systematically recorded. RESULTS: At four months,
      Melissa officinalis extract produced a significantly better outcome on cognitive
      function than placebo (ADAS-cog: df = 1, F = 6.93, p = 0.01; CDR: df = 1, F =
      16.87, p < 0.0001). There were no significant differences in the two groups in
      terms of observed side effects except agitation, which was more common in the
      placebo group (p = 0.03). CONCLUSIONS: Melissa officinalis extract is of value in
      the management of mild to moderate Alzheimer's disease and has a positive effect
      on agitation in such patients.

PMID- 12810769
TI  - The prevalence of frontal variant frontotemporal dementia and the frontal lobe
      syndrome in a population based sample of 85 year olds.
AB  - OBJECTIVES: To investigate the prevalence of the frontal lobe syndrome (FLS) and
      the frontal variant of frontotemporal dementia (fvFTD) in a population based
      sample of 85 year olds. METHODS: A representative sample of 85 year olds (n =
      451) in Gothenburg, Sweden was examined with a neuropsychiatric examination and a
      key informant interview performed by an experienced psychiatrist. A subsample
      underwent computed tomography (CT) of the head. The Lund-Manchester research
      criteria were used as a basis for a symptom algorithm to identify individuals
      with FLS and fvFTD. These were diagnosed blindly to the diagnosis of dementia
      according to DSM-III-R. RESULTS: A total of 86 individuals (19%) fulfilled the
      criteria for FLS, and 14 of them fulfilled criteria for fvFTD. There were no
      differences between men and women. Among those with FLS, 75 (87%) fulfilled DSM
      III-R criteria for other types of dementia, mainly Alzheimer's disease and
      vascular dementia. Among the 14 fvFTD cases, only five were demented according to
      DSM-III-R. Moderate to severe frontal atrophy was found in 93% of those with FLS
      (and in all cases with fvFTD), but also in 49% of those without FLS. FLS was
      found in 35% of those with moderate to severe frontal atrophy, and in 3% of those
      without these changes. CONCLUSIONS: The prevalence of fvFTD was 3% in 85 year
      olds, which is higher than previously expected in this age group. Only a minority
      of those with fvFTD were detected by the DSM-III-R criteria for dementia. FLS was
      even more common, especially in those diagnosed with a dementia disorder.

PMID- 12810770
TI  - Cognitive presentation of multiple sclerosis: evidence for a cortical variant.
AB  - BACKGROUND: Although neuropsychiatric complications are well recognised, the
      presentation of multiple sclerosis with cognitive or neuropsychiatric symptoms
      has generally been considered a rare occurrence and to reflect subcortical
      pathology. OBJECTIVES: To document the clinical, neuropsychological, and
      radiological features of six cases of cognitive presentation of multiple
      sclerosis, to review the relevant literature, and to propose a possible cortical
      basis for this clinical presentation. SUBJECTS: Six patients (five women; age
      range 38 to 60 years) presented to the memory and cognitive disorders clinic in
      Cambridge with an initially undiagnosed cognitive/neuropsychiatric syndrome. All
      underwent neuropsychological evaluation, brain imaging, and ancillary
      investigations to establish a diagnosis of multiple sclerosis. RESULTS: The six
      cases all had a progressive dementia syndrome with prominent amnesia, often
      accompanied by classic cortical features including dysphasia, dysgraphia, or
      dyslexia. Mood disturbance was ubiquitous and in three patients there was a long
      history of preceding severe depression. All six developed characteristic physical
      signs on follow up, with marked disabilities. A review of 17 previously reported
      cases highlighted the prominence of memory impairment and depression in the early
      stages. CONCLUSIONS: On clinical, pathological, and radiological grounds, the
      neuropsychiatric presentation of multiple sclerosis may represent a
      clinicopathological entity of "cortical multiple sclerosis." Failure to recognise
      this will delay diagnosis and may expose patients to potentially dangerous and
      invasive investigation. Because the neuropsychiatric features of cortical
      multiple sclerosis are a major cause of handicap, their early recognition may be
      particularly important in view of emerging treatments.

PMID- 12810771
TI  - Longitudinal study of cognitive dysfunction in multiple sclerosis:
      neuropsychological, neuroradiological, and neurophysiological findings.
AB  - OBJECTIVE: (1) To assess cognitive function and cerebral magnetic resonance
      imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to
      monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over
      time (mean 8.5 year follow up period); (3) to study the relation between
      clinical, neuropsychological, and MRI data. On follow up assessment, visual and
      auditory oddball event related potentials (ERPs) were recorded as
      psychophysiological evaluation of cognitive status. Correlations between
      neuropsychological, MRI, and ERP data were also analysed. METHODS:
      Neuropsychological study assessed verbal and non-verbal IQ, deterioration index
      (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial
      short-term and long term memory. MRI assessment detected presence of
      demyelinating lesions by using a semiquantitative method as well as cortical and
      subcortical atrophy over time. RESULTS: Attention, short-term and long term
      visuospatial memory were mildly impaired at baseline and remained unaltered
      longitudinally. At retesting a significant worsening of verbal long term memory
      (p=0.023), DI presence (p=0.041) and the increase of supratentorial and
      subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale
      score correlated significantly with total lesion burden at both evaluations
      (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions
      as well as cortical atrophy correlated significantly with attention and memory
      tests at baseline. Follow up assessment revealed significant correlation between
      cortical atrophy and attention as well as visuospatial short-term memory; spatial
      long term memory correlated significantly with lesions in body of lateral
      ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of
      patients, involving specifically more visual P300 (58.4 % of cases) than auditory
      wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI
      and auditory P300 latency with frontal horn and brain stem lesions. CONCLUSIONS:
      These findings revealed mild cognitive impairment in MS patients particularly
      consistent with slowing information processing over time. Increased MRI lesions
      do not correlate with the clinical course of the disease and cognitive deficit
      evolution. Thus, cognitive dysfunction could be related to disease peculiarity
      and not to the time course. Correlations between P300, neuropsychological, and
      MRI findings provide further information about ERP application to examine
      cognitive impairment in MS and probably to investigate their neural origin.

PMID- 12810772
TI  - Differences in the diagnostic accuracy of acute stroke clinical subtypes defined
      by multimodal magnetic resonance imaging.
AB  - BACKGROUND: Despite its importance for acute stroke management, little is known
      about the underlying pathophysiology when patients with acute stroke are
      classified using clinical methods. OBJECTIVE: To examine the relation between the
      magnetic resonance defined stroke subtype and clinical stroke classifications
      using diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), and
      angiographic magnetic resonance techniques. METHODS: Consecutive patients with
      clinical syndromes consistent with acute anterior circulation stroke were
      assessed clinically within six hours of onset and scanned as soon as possible
      using multimodal magnetic resonance imaging (MRI). Patients were classified
      clinically into total or partial anterior circulation syndromes using the Oxford
      classification, or according the severity of the National Institutes of Health
      stroke scale (NIHSS) (severe > 15; mild/moderate <or= 15). At day seven, patients
      were classified by combining clinical course and MRI data as misdiagnosed,
      misclassified, suffering transient ischaemic attack, infarct with recanalisation,
      or infarction with persisting occlusion. Patients with occlusion were further
      divided on the basis of a large diffusion-perfusion mismatch. RESULTS: 84
      patients with clinical anterior circulation syndromes were studied. Using the
      NIHSS, 42 were mild to moderate (0-15) and 42 were severe (> 15). There were 42
      with partial anterior circulation syndromes (PACS) and 42 with total anterior
      circulation syndromes (TACS). Patients with TACS or severe stroke were more
      likely to have actually suffered a stroke (Fischer's exact test, p = 0.01), to
      have a correctly classified stroke (chi(2) 28.2, p < 0.01), to have persisting
      occlusion (chi(2) 30.6, p < 0.01), and to have a large DWI-PWI mismatch (chi(2)
      17.1, p < 0.01). CONCLUSIONS: There is more inaccuracy in patients presenting
      with acute PACS or clinically mild to moderate anterior circulation stroke than
      in those with TACS or severe acute stroke syndromes. The latter appear more
      likely to be the targets for acute stroke interventions, as they include a
      significantly higher proportion of patients with persisting occlusion and
      diffusion/perfusion mismatch.

PMID- 12810773
TI  - Lack of hemispheric dominance for consciousness in acute ischaemic stroke.
AB  - BACKGROUND: Previous reports have suggested left hemispheric dominance for
      maintaining consciousness, although there is controversy over this claim.
      OBJECTIVE: To compare early impairment of level of consciousness between patients
      with right and left hemispheric stroke. METHODS: Data from 564 patients with
      ischaemic stroke enrolled in the placebo arm of a trial of a putative
      neuroprotectant were analysed. All patients had major hemispheric stroke with
      cortical dysfunction, visual field deficit, and limb weakness, with symptom onset
      within 12 hours of enrolment. Patients were prospectively evaluated on a
      predefined scale (1-6; 1 = fully awake, higher scores representing greater
      impairment) to measure level of consciousness at multiple time points over the
      initial 24 hours after presentation. The National Institutes of Health (NIH)
      stroke scale score at presentation and infarct volume at 30 days were determined.
      RESULTS: Some degree of impairment in level of consciousness was observed in 409
      of the 564 patients (73%). Median maximum sedation score was 2 for both right and
      left hemispheric stroke (p = 0.91). Mean sedation score over 24 hours was 1.5 for
      both right and left stroke (p = 0.75). There was no difference between level of
      consciousness scores in right and left stroke at any individual time point during
      the 24 hour monitoring period. No association between side and impairment in
      level of consciousness was seen after adjustment for stroke severity and infarct
      volume. CONCLUSIONS: In contrast to previous reports, there was no evidence for
      hemispheric dominance for consciousness in the setting of a major hemispheric
      stroke.

PMID- 12810774
TI  - The outcome of depressive disorders in neurology patients: a prospective cohort
      study.
AB  - BACKGROUND: In a previous prospective study of 300 consecutive new attenders at
      neurology outpatient clinics, depressive disorders were diagnosed in 119 patients
      (40%) and major depressive disorder in 77 (26%). OBJECTIVE: To describe the eight
      month outcome of depression in this cohort. METHODS: Patients were reinterviewed
      eight months after their baseline assessment. Mental state was examined using the
      primary care evaluation of mental disorders (PRIME-MD) interview and the hospital
      anxiety and depression (HAD) self rating scale. Health status was measured using
      the medical outcome study 36 item short form scale (SF-36). RESULTS: Of the
      original cohort of 300, 226 (75%) participated in the follow up. Among them, 88
      had a depressive disorder at baseline and 69 (78%) of those were still depressed
      at follow up; 54 had major depression at baseline and 46 (85%) of those still had
      a major depressive disorder at follow up. Among the 138 patients who had no
      depression at baseline, 20 new major depressive disorders had developed by the
      time of follow up. Resolution of major depressive disorders was associated with
      an improvement in health status. CONCLUSIONS: Most depressive disorders detected
      in neurology outpatients persist at an eight month follow up, and a substantial
      number of new cases arise. Resolution of depressive disorders, particularly major
      depressive disorder, is associated with an improvement in health status.

PMID- 12810775
TI  - The outcome of neurology outpatients with medically unexplained symptoms: a
      prospective cohort study.
AB  - BACKGROUND: In a previous cross sectional study of 300 consecutive new attenders
      at neurology outpatient clinics, 90 were detected with symptoms that were rated
      as "not at all" or only "somewhat" explained by organic disease. OBJECTIVE: To
      report a follow up study of this cohort. METHODS: Patients were reinterviewed by
      telephone eight months after their initial assessment. They were asked to rate
      their overall improvement on a clinical global improvement scale, and their
      health status on the medical outcome short form 36 item scale (SF-36). The PRIME
      MD interview was administered to determine psychiatric diagnoses. Neurological
      and primary care records were reviewed for any changes in diagnostic opinion
      during the follow up period. RESULTS: Of the 90 eligible patients, 66 (73%)
      participated in follow up. Among these, five (8%) rated themselves as "much
      worse," four (6%) as "somewhat worse," 27 (40%) as "just the same," 15 (23%) as
      "somewhat better," and 15 (23%) as "much better." There were no cases in which an
      organic cause for the presenting complaint was uncovered during the follow up
      period. Poorer physical function at baseline was the only predictor of poorer
      outcome at follow up. CONCLUSIONS: Over half the patients who presented to
      neurologists with symptoms that were rated as largely or completely medically
      unexplained had not improved eight months later. In no case was a disease
      explanation for the original presenting symptoms subsequently identified.

PMID- 12810777
TI  - Spontaneous haemorrhage into metastatic brain tumours after stereotactic
      radiosurgery using a linear accelerator.
AB  - OBJECTIVE: To determine the incidence and clinical characteristics of spontaneous
      haemorrhage into metastatic brain tumours after radiosurgery. METHODS:
      Intratumour haemorrhage rate, clinical features, and treatment were evaluated in
      54 patients with 131 brain metastases of varying origin who were treated using
      linear accelerator radiosurgery. The marginal dose was maintained constant at 20
      or 25 Gy, irrespective of tumour size. RESULTS: Haemorrhage was identified in
      7.4% of the metastases (five tumours in four patients) before radiosurgery and in
      18.5% (10 tumours in 10 patients) after radiosurgery. In three cases, haemorrhage
      into the tumour after radiosurgery was symptomatic. Half the haemorrhages
      occurred within one month of radiosurgery. The changes in tumour size observed at
      the time of haemorrhage were an increase in one tumour, no change in five, and a
      decrease in four. Haemorrhage into a tumour after radiosurgery was more likely to
      occur in female patients, in tumours with a larger volume on pretreatment
      neuroimaging, and in tumours treated with a larger number of isocentres or a
      higher maximum dose. Haemorrhagic features in the patients or their tumours on
      presurgical assessment were not disposing factors to haemorrhage after
      radiosurgery. CONCLUSIONS: When larger brain metastases are aggressively treated
      by radiosurgery, better local control may be attained but there may also be a
      higher risk of haemorrhage soon after the treatment.

PMID- 12810776
TI  - Functional recovery after surgical resection of low grade gliomas in eloquent
      brain: hypothesis of brain compensation.
AB  - OBJECTIVES: To describe functional recovery after surgical resection of low grade
      gliomas (LGG) in eloquent brain areas, and discuss the mechanisms of
      compensation. METHODS: Seventy-seven right-handed patients without deficit were
      operated on for a LGG invading primary and/or secondary sensorimotor and/or
      language areas, as shown anatomically by pre-operative MRI and intraoperatively
      by electrical brain stimulation and cortico-subcortical mapping. RESULTS: Tumours
      involved 31 supplementary motor areas, 28 insulas, 8 primary somatosensory areas,
      4 primary motor areas, 4 Broca's areas, and 2 left temporal language areas. All
      patients had immediate post-operative deficits. Recovery occurred within 3 months
      in all except four cases (definitive morbidity: 5%). Ninety-two percent of the
      lesions were either totally or extensively resected on post-operative MRI.
      CONCLUSIONS: These findings suggest that spatio-temporal functional re
      organisation is possible in peritumoural brain, and that the process is dynamic.
      The recruitment of compensatory areas with long term perilesional functional
      reshaping would explain why: before surgery, there is no clinical deficit despite
      the tumour growth in eloquent regions; immediately after surgery, the occurrence
      of a deficit, which could be due to the resection of invaded areas participating
      (but not essential) to the function; and why three months after surgery, almost
      complete recovery had occurred. This brain plasticity, which decreases the long
      term risk of surgical morbidity, may be used to extend the limits of surgery in
      eloquent areas.

PMID- 12810779
TI  - Long term course of the H reflex after selective tibial neurotomy.
AB  - OBJECTIVES: This study was conducted to evaluate the long term clinical and
      electrophysiological outcome by recording the H reflex in a consecutive series of
      six patients treated by selective tibial neurotomy for spastic equinus foot.
      METHOD: The amplitudes of Hmax reflexes, Mmax responses, and Hmax:Mmax ratio were
      recorded in six patients with chronic lower limb spasticity, before and after
      surgery, at day 1 and 8 months and 24 months after selective tibial neurotomy.
      The passive range of movement, the stretch reflex score according to the Tardieu
      scale, the osteoarticular and tendon repercussions, and the quality of motor
      control of dorsiflexion were evaluated preoperatively and postoperatively.
      RESULTS: At the end of the study, all patients presented a reduction of equines.
      Gait and Tardieu's score of spasticity had improved in all patients. Active
      dorsiflexion of the ankle was unchanged in four patients, but two improved by 5
      degrees to 12 degrees. In five cases, fascicular resection of the superior nerve
      to soleus was, alone, sufficient to reduce spastic equinus foot, without
      recurrence, for a mean follow up of 28 months. Two patients were reoperated on,
      one for remaining spasticity related to an underestimated spasticity of the
      gastrocnemius muscles, and the other for painful claw toes. Hmax, Mmax, and
      Hmax:Mmax ratios were significantly lower the day after surgery. The reduction of
      Hmax and Hmax/Mmax ratio remained stable over time and was still statistically
      significant two years after the operation. However, the value of Mmax eight
      months postoperatively was no longer significantly different from the
      preoperative value. CONCLUSION: This study shows the long term efficacy of the
      selective tibial neurotomy as treatment of spastic equinus foot. Neurotomy
      confined to fibres supplying the soleus muscle is sufficient in most cases and
      acts by decreasing sensory afferents without significant long term motor
      denervation.

PMID- 12810780
TI  - New evidence for an association between the CSF HVA:5-HIAA ratio and psychopathic
      traits.
AB  - OBJECTIVES: To replicate the relation between the CSF HVA:5-HIAA ratio and
      psychopathic traits previously reported in a pilot group of 22 perpetrators of
      violent crimes. METHODS: CSF monoamine metabolite concentrations in another 28
      violent and sexual offenders, aged 45 or below, referred to pretrial forensic
      psychiatric investigation, were compared to features of psychopathy according to
      the Psychopathy Checklist-Revised (PCL-R). RESULTS: Our previous finding was
      repeated in the new study group, where the HVA:5-HIAA ratio was strongly
      associated with psychopathic traits (r = 0.50, p = 0.010), particularly its
      behavioural aspects (r = 0.523, p = 0.004). In subsamples of individuals from
      both study groups who had no medication (n = 25) or no current axis I disorder,
      including a history of mood disorder or substance dependence (n = 21), the HVA:5
      HIAA ratio remained strongly associated with all psychopathy factors but most
      closely with the behavioural features. Retrospective assessments of childhood
      disruptive symptomatology, such as attention deficit hyperactivity disorder or
      conduct disorder, analysed in relation to the monoamine metabolites, showed the
      same association with the HVA:5-HIAA ratio. CONCLUSIONS: Violent and aggressive
      behavioural traits with childhood onset and adult expression as psychopathic
      features are associated with changed activity in the brain dopaminergic system,
      possibly as a result of serotonergic dysregulation.

PMID- 12810781
TI  - Observer independent analysis of cerebral glucose metabolism in patients with
      chronic fatigue syndrome.
AB  - OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18
      fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with
      chronic fatigue syndrome (CFS), using an observer independent analytical
      approach; and to characterise any observed alterations by correlating them with
      neuropsychological deficits. METHODS: 26 patients (13 female, 13 male) were
      examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages
      ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent
      extensive psychometric testing including the hospital anxiety and depression
      scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG
      PET was done in all the subjects. After stereotactic normalisation, single
      subject comparisons with an age and sex matched normal database (n = 18) and a
      group comparison between the patients and normal controls were undertaken, along
      with additional correlation analyses between brain metabolism and psychometric
      test scores. RESULTS: 12 of the 26 patients showed no significant decrease in FDG
      uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism
      bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five
      of these 12 patients also had decreased metabolism in the orbitofrontal cortex.
      The two remaining patients had hypometabolism in the cuneus/praecuneus.
      Correlation analyses showed significant correlations between some test scores
      (anxiety, depression, health related quality of life) but not fatigue and
      regional reductions in glucose metabolism. CONCLUSIONS: Although abnormalities in
      FDG-PET were only detectable in approximately half the CFS patients examined, and
      no specific pattern for CFS could be identified, PET may provide valuable
      information in helping to separate CFS patients into subpopulations with and
      without apparent alterations in the central nervous system.

PMID- 12810782
TI  - Early diagnosis of external ventricular drainage infection: results of a
      prospective study.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of total drainage
      time on the risk of catheter infection, and the predictive value of standard
      laboratory examinations for the diagnosis of bacteriologically recorded
      cerebrospinal fluid (CSF) infection during external ventricular drainage.
      METHODS: During a three year period, all patients of the neurosurgical intensive
      care unit (ICU), who received an external ventricular drain, were prospectivly
      studied. Daily CSF samples were obtained and examined for cell count, glucose and
      protein content. Bacteriological cultures were taken three times a week, and
      serum sepsis parameters were determined. RESULTS: 130 patients received a total
      of 186 external ventricular drains. The ventricular catheters were in place from
      one to 25 days (mean 7.1 days). In 1343 days of drainage, the authors recorded 41
      positive bacteriological cultures in 21 patients between the first and the 22nd
      drainage day (mean 6.4). No significant correlation was found between drainage
      time and positive CSF culture. The only parameter that significantly correlated
      with the occurrence of a positive CSF culture was the CSF cell count (unpaired t
      test, p<0.05). CONCLUSIONS: Drainage time is not a significant risk factor for
      catheter infection. Increasing CSF cell count should lead to the suspicion of
      bacteriological drainage contamination. Other standard laboratory parameters,
      such as peripheral leucocyte count, CSF glucose, CSF protein, or serum sepsis
      parameters, are not reliable predictors for incipient ventricular catheter
      infection.

PMID- 12810783
TI  - Cognitive dysfunction in young men following head injury in childhood and
      adolescence: a population study.
AB  - OBJECTIVES: To examine the prevalence of cognitive dysfunction among young men
      who had suffered a head injury during childhood or adolescence, in particular
      focusing upon the effects of age and the severity of the injury. METHODS: By
      cross linkage of Danish national registers for hospital admissions and the draft
      board, 3091 young men were identified who had been injured before age 18 and
      tested at age 18 or shortly thereafter: 970 had suffered a single concussion and
      were in hospital for one day only; 521 had two concussions at separate times and
      were in hospital for one day only on each occasion; 961 had a cranial fracture;
      and 639 had a cerebral lesion. For all of these, scores on the draft board's
      cognitive screening test were obtained, dichotomised as dysfunctional or non
      dysfunctional. Prevalences of dysfunctional scores were compared with population
      base rates (about 20% of all Danish men appearing before the draft board had a
      score classified as dysfunctional). RESULTS: For young men who had suffered a
      single concussion, cranial fracture, or cerebral lesion before 12 years of age,
      resulting in less than 12 days of hospital admission (n = 376), rates of
      cognitive dysfunction did not exceed those in the general population (odds ratios
      < 1.4, NS), but the odds ratios became significant and > 1.4 where the injury
      occurred after age 11. For those with a cerebral lesion resulting in over 11 days
      of hospital admission (n = 263), all odds ratios were significant and >or= 2.0,
      irrespective of age at injury. For cases of two concussions, all odds ratios were
      > 1.4 but were not significant for all age groupings. CONCLUSIONS: For milder
      forms of single head injury before age 12 there is no evidence of enduring
      cognitive dysfunction. The apparent effect at later ages may reflect predisposing
      psychosocial factors. For more serious injury, and for cases with two
      concussions, the effect is marked and not clearly related to age. For the former,
      this suggests enduring neurological effects of the injury; for the latter, where
      the effect is unrelated to time between injuries, predisposing factors may again
      play a role.

PMID- 12810784
TI  - Outcome of contemporary surgery for chronic subdural haematoma: evidence based
      review.
AB  - OBJECTIVE: To evaluate the results of surgical treatment options for chronic
      subdural haematoma in contemporary neurosurgery according to evidence based
      criteria. METHODS: A review based on a Medline search from 1981 to October 2001
      using the phrases "subdural haematoma" and "subdural haematoma AND chronic".
      Articles selected for evaluation had at least 10 patients and less than 10% of
      patients were lost to follow up. The articles were classified by three classes of
      evidence according to criteria of the American Academy of Neurology. Strength of
      recommendation for different treatment options was derived from the resulting
      degrees of certainty. RESULTS: 48 publications were reviewed. There was no
      article that provided class I evidence. Six articles met criteria for class II
      evidence and the remainder provided class III evidence. Evaluation of the results
      showed that twist drill and burr hole craniostomy are safer than craniotomy; burr
      hole craniostomy and craniotomy are the most effective procedures; and burr hole
      craniostomy has the best cure to complication ratio (type C recommendation).
      Irrigation lowers the risk of recurrence in twist drill craniostomy and does not
      increase the risk of infection (type C recommendation). Drainage reduces the risk
      of recurrence in burr hole craniostomy, and a frontal position of the drain
      reduces the risk of recurrence (type B recommendation). Drainage reduces the risk
      of recurrence in twist drill craniostomy, and the use of a drain does not
      increase the risk of infection (type C recommendation). Burr hole craniostomy
      appears to be more effective in treating recurrent haematomas than twist drill
      craniostomy, and craniotomy should be considered the treatment of last choice for
      recurrences (type C recommendation). CONCLUSIONS: The three principal techniques
      twist drill craniostomy, burr hole craniostomy, and craniotomy-used in
      contemporary neurosurgery for chronic subdural haematoma have different profiles
      for morbidity, mortality, recurrence rate, and cure rate. Twist drill and burr
      hole craniostomy can be considered first tier treatment, while craniotomy may be
      used as second tier treatment. A cumulative summary of data shows that, overall,
      the postoperative outcome of chronic subdural haematoma has not improved
      substantially over the past 20 years.

PMID- 12810785
TI  - The role of the PTPRC (CD45) mutation in the development of multiple sclerosis in
      the North West region of the United Kingdom.
AB  - BACKGROUND: A point mutation in protein tyrosine phosphatase receptor, type c
      polypeptide (PTPRC) has been associated with familial multiple sclerosis. This CG
      mutation at position 77 of exon 4 results in altered expression of CD45 isoforms
      on immune cells. OBJECTIVE: To study the incidence of PTPRC mutations in subjects
      with multiple sclerosis in the North West region of the United Kingdom. METHODS:
      Affected and unaffected subjects from five pedigrees with familial multiple
      sclerosis, 330 non-familial cases of multiple sclerosis, and 197 controls were
      studied. Genomic DNA was amplified using CD45IE34 and CD45IE44 primers, digested
      with Mspl, and run on an agarose gel. Polymerase chain reaction products were
      sequenced to exclude any other mutations. RESULTS: No PTPRC exon 4 genomic
      mutations were seen in any of the five families. In the non-familial cases the
      incidence of mutation was 4.1% in 197 controls and 5.1% in 330 multiple sclerosis
      patients. No significant association was found in this study with this mutation
      and disease susceptibility, sex, or an extended disability scale score of < 5.5.
      CONCLUSIONS: This candidate does not appear to influence the development of
      familial multiple sclerosis in this population. The negative result could arise
      from a type II error owing to the number of families and non-familial cases
      screened. Alternatively it might suggest that the contribution of the PTPRC
      mutation depends upon the genetic background.

PMID- 12810786
TI  - Interferon beta in multiple sclerosis: experience in a British specialist
      multiple sclerosis centre.
AB  - BACKGROUND: The efficacy of interferon beta (IFN beta) is well established in
      relapsing-remitting multiple sclerosis (MS). However, the use of this drug in
      clinical practice is complex, especially because it is only partially effective,
      its long term efficacy and side effects are unknown, its efficacy may be
      abrogated by the development of neutralising antibodies, compliance is variable,
      and its cost effectiveness is controversial. OBJECTIVES AND METHODS: Analysis of
      a prospectively followed up series of 101 MS patients treated with IFN beta was
      undertaken to: (1) monitor the outcome of IFN beta treatment in clinical
      practice; (2) compare the immunogenicity of the three commercial IFN beta
      preparations available; (3) assess the proportion of patients fulfilling the
      current guidelines of the Association of British Neurologists for stopping IFN
      beta therapy. RESULTS: During a median treatment period of 26 months (range 2
      85), the relapse rate decreased by 41%. Although the reduction in the relapse
      rate was similar for all three commercial products, none of the Avonex treated
      patients were relapse free, compared with 19% of the Betaferon treated and 27% of
      the Rebif treated patients (p=0.02). Neutralising antibodies were not detected in
      Avonex treated patients (0 of 18), compared with 12 of 32 (38%) Betaferon treated
      and 10 of 23 (44%) Rebif treated patients (p=0.02). Forty of 101 (40%) patients
      satisfied the current (2001) Association of British Neurologists criteria for
      stopping IFN beta treatment at some stage during their treatment. CONCLUSION: IFN
      beta is effective in reducing the relapse rate in patients with relapsing
      remitting MS in routine clinical practice. However, after a median treatment
      duration of 26 months, 40% of initially relapsing-remitting MS patients seem to
      have ongoing disease activity, presenting as disabling relapses or insidious
      progression.

PMID- 12810789
TI  - Low leucocyte myeloperoxidase activity in patients with multiple sclerosis.
AB  - The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis
      (MS). By measuring H(2)O(2) dependent oxidation of 3,3'5,5'-tetramethylbenzidine
      with spectrophotometry the authors investigated MPO activity in peripheral blood
      leucocytes from 42 patients with MS (12 with secondary progressive MS, 17 with
      primary progressive MS, and 13 with relapsing remitting benign MS) and 32 healthy
      controls. Leucocyte MPO activity was significantly lower in patients with benign
      MS (mean (SEM) 0.086 (0.029) U/mg protein; p<0.01), secondary progressive MS
      (0.038 (0.009) U/mg protein; p<0.001), and primary progressive MS (0.057 (0.016)
      U/mg protein; p<0.001) compared with healthy controls (0.322 (0.053) U/mg
      protein). These data suggest that low MPO, which may be genetically determined,
      plays a part in MS pathogenesis.

PMID- 12810788
TI  - MRI lesion volume heterogeneity in primary progressive MS in relation with axonal
      damage and brain atrophy.
AB  - OBJECTIVES: To investigate whether axonal damage in primary progressive (PP)
      multiple sclerosis (MS), as measured by proton magnetic resonance spectroscopy
      (HMRS) imaging and brain atrophy, is a function of T2 weighted brain lesion
      volume. METHODS: 34 PP MS patients were divided into two categories: low (<3
      cm(3), n = 18) or high (>or=3 cm(3), n = 16) T2 lesion load (LL). An Index of
      Brain Atrophy (IBA) was calculated and HMRS metabolite ratios were derived from a
      central brain area centred at the corpus callosum. RESULTS: Patient groups did
      not differ with regard to clinical characteristics and showed lower mean IBA and
      mean N-acetylaspartate:creatinine (NAA:Cr) ratios compared to healthy controls.
      CONCLUSION: PP patients with low and high brain T2LL have detectable brain
      atrophy and NAA:Cr reduction compared to healthy controls. In PP MS, T2 lesions
      alone are insufficient to explain the presence of brain atrophy and decrease in
      NAA:Cr.

PMID- 12810790
TI  - Olfactory deficits and sleep disturbances in Parkinson's disease: a case-control
      survey.
AB  - BACKGROUND: Olfactory and sleep disturbances are common in Parkinson's disease,
      and may be early disease indicators. OBJECTIVE: To obtain information about
      olfactory and sleep deficits preceding the onset of motor symptoms in Parkinson's
      disease. SUBJECTS: 38 community dwelling patients with Parkinson's disease (73%
      response rate) and 32 age matched controls (60% response rate). METHODS: Using a
      questionnaire survey, the frequencies, timing, and relations between olfactory
      and sleep disturbances, drug treatment, mood, and motor deficits in Parkinson's
      disease were compared with those in age matched controls. Reliability of
      information was validated by informant interview in 9% of the sample.
      Interdependency of factors was assessed using Fisher's fourfold table test, and
      differences between populations were analysed using chi(2) and unpaired t tests.
      RESULTS: Microsmia was reported by 26 patients (68%) (and only one control), on
      average within a year of the diagnosis of Parkinson's disease. More patients than
      controls had excessive daytime somnolence (45% v 6%), restless legs (50% v 19%),
      and abnormal movements during sleep (34% v 0%), which generally occurred three to
      five years after diagnosis and were independent of mood disorders and drug
      treatment. CONCLUSIONS: Many patients with Parkinson's disease have microsmia at
      the onset of motor deficits, but some sleep disorders are a subsequent
      occurrence.

PMID- 12810791
TI  - Low vitamin B-12 status in confirmed Alzheimer's disease as revealed by serum
      holotranscobalamin.
AB  - OBJECTIVE: To examine the possible association of holotranscobalamin, the active
      fraction of serum cobalamin, with Alzheimer's disease. METHODS: 51 patients with
      pathologically confirmed Alzheimer's disease and 65 cognitively screened elderly
      controls were studied. Serum holotranscobalamin was measured by a new solid phase
      radioimmunoassay. RESULTS: Geometric mean levels showed no significant case
      control differences for serum total cobalamin, but lower levels of
      holotranscobalamin in Alzheimer's disease (41.1 pmol/l) than in controls (57.1
      pmol/l) (p < 0.001). The odds ratio of Alzheimer's disease was significant for
      low holotranscobalamin but not for low total cobalamin. CONCLUSIONS: Disturbed
      cobalamin status is common in Alzheimer's disease and accordingly measurement of
      holotranscobalamin should be considered in the assessment of cognitively impaired
      patients.

PMID- 12810792
TI  - Similarity and disparity of obsessive-compulsive disorder and schizophrenia in MR
      volumetric abnormalities of the hippocampus-amygdala complex.
AB  - OBJECTIVES: Given that obsessive-compulsive disorder (OCD) and schizophrenia may
      share clinical symptoms as well as functional brain abnormalities, this study was
      designed to clarify common and different morphological abnormalities in OCD and
      schizophrenia. METHODS: Volumes of the hippocampus, the amygdala, and the
      thalamus were measured in three age and sex matched groups of 22 patients with
      OCD, 22 patients with schizophrenia, and 22 normal subjects using three
      dimensional magnetic resonance imaging. Volume tracing was performed manually on
      serial coronal slices with the references of sagittal or axial planes using
      internal landmarks. RESULTS: Hippocampal volume was bilaterally reduced in both
      OCD and schizophrenic patients versus the normal controls. Left amygdala volume
      was significantly enlarged in patients with OCD but not in patients with
      schizophrenia versus the normal controls. The thalamus did not show any
      volumetric group differences. CONCLUSIONS: Non-specific hippocampal reduction in
      both the OCD and schizophrenic groups is likely to link to a clinical overlap
      between the two illnesses, whereas the left amygdala enlargement observed only in
      the OCD patients seems to be suggestive of a unique role for the amygdala in the
      pathophysiology of OCD.

PMID- 12810794
TI  - Alterations of muscarinic acetylcholine receptors in atypical Pick's disease
      without Pick bodies.
AB  - BACKGROUND: Atypical Pick's disease without Pick bodies is a type of
      frontotemporal dementia characterised by semantic dementia and temporal dominant
      lobar atrophy with ubiquitinopathy. No neurochemical analyses have ever been
      reported in this condition. OBJECTIVE: To investigate muscarinic acetylcholine
      receptors (mAchR) and their subtypes (M1-M4) in atypical Pick's disease.
      SUBJECTS: Five cases of atypical Pick's disease were studied. They were compared
      with nine control cases, 11 cases of Alzheimer's disease, and seven cases of
      dementia with Lewy bodies. METHODS: A [(3)H]quinuclidinyl benzilate (QNB) binding
      assay and an immunoprecipitation assay using subtype specific antisera were used.
      RESULTS: The total amount of mAchR in the temporal cortex was lower in atypical
      Pick's disease than in controls or Alzheimer's disease cases, but there were no
      significant differences between the three groups in the frontal cortex. In the
      temporal cortex, there was a smaller proportion of M1 receptors in atypical
      Pick's disease than in the controls or in the patients with Alzheimer's disease
      and dementia with Lewy bodies. In contrast, the proportion of M2 receptor was
      higher in atypical Pick's disease than in the other three groups. CONCLUSIONS:
      Depletion of postsynaptic cholinoreceptive neurones in the temporal cortex is
      more severe in atypical Pick's disease than in other neurodegenerative dementing
      disorders.

PMID- 12810795
TI  - Genetically confirmed clinical Huntington's disease with no observable cell loss.
AB  - Huntington's disease (HD) results from neurodegeneration of the neostriatum. The
      mutation on chromosome 4 is an expansion in a triplet repeat (CAG)(n) located
      within the IT15 gene. Only six patients have been reported with clinical features
      of HD in association with limited neuropathology. Of these, only one has had the
      diagnosis confirmed by genetic (DNA) testing. We describe a patient with the
      clinical phenotype and genetically confirmed HD but unexpected limited
      neuropathology. The patient was seen because of aggressive behaviour and memory
      problems of two years duration. The differential diagnosis included HD although
      there was no family history. DNA testing was positive for the HD mutation.
      Clinical follow up three months later confirmed classic features of HD.
      Progression of the disease was rapid with death three years later. Neuropathology
      revealed a largely intact neostriatum with bilateral ischaemic damage and cell
      loss in the external globus pallidus. Such pathology alone could explain the
      clinical features of HD. This is only the second report of genetically confirmed
      clinically manifest HD with little evidence of HD neuropathology. There are
      several unusual features which could not have been predicted by the clinical
      picture, in particular the progressive course of bilateral ischaemic changes
      restricted to the external globus pallidus. The potential to miss other HD cases
      at post-mortem examination, and the implications of this for family members, are
      discussed.

PMID- 12810796
TI  - Apolipoprotein E genotypes and clinical outcome in Guillain-Barre syndrome.
AB  - BACKGROUND: Polymorphism of the gene encoding the cholesterol transport protein
      apolipoprotein E (APOE, gene; apoE, protein), known to be involved in axonal
      regeneration and remyelination, influences outcome after a variety of central
      nervous system disorders. Apolipoprotein E gene polymorphisms could affect
      recovery from Guillain-Barre syndrome. OBJECTIVE: To correlate APOE genotypes
      with residual disability and degree of improvement in Guillain-Barre syndrome,
      assessed one year after presentation METHODS: 91 patients with the syndrome were
      recruited from southeast England and their APOE genotypes were determined.
      RESULTS: There were no clear differences in APOE genotype or allele frequencies
      when comparing the 91 patients with controls, nor when comparing 81 patients with
      good outcome and 10 with poor outcome. CONCLUSIONS: APOE genotype did not
      influence susceptibility to Guillain-Barre syndrome or recovery from it. This may
      be because our sample size of 91 was not sufficiently large to detect small
      differences in recovery associated with different APOE genotypes, or because
      cholesterol transportation is not a crucial rate limiting step in peripheral
      nerve regeneration.

PMID- 12810797
TI  - Atypical herpes type 2 encephalitis associated with normal MRI imaging.
AB  - We describe a case of chronic atypical herpes simplex type 2 encephalitis in an
      immunocompromised 68 year old man presenting with headache and cognitive changes
      without focal neurological or MRI findings. To our knowledge this is the first
      described case of herpes simplex encephalitis associated with normal MRI brain
      imaging and non-focal neurological examination. This further expands the range of
      clinical presentations that may be associated with herpes simplex encephalitis
      and emphasises the value of PCR for herpes simplex virus in the investigation of
      encephalitis regardless of imaging findings.

PMID- 12810799
TI  - Wallerian degeneration of the inferior cerebellar peduncle depicted by diffusion
      weighted imaging.
AB  - Wallerian degeneration of the inferior cerebellar peduncle has never been
      demonstrated on imaging studies. We describe a case in which it was depicted by
      thin slice diffusion weighted imaging. Location to the inferior cerebellar
      peduncle was confirmed by a fibre tracking method.

PMID- 12810801
TI  - Vocal fold motion impairment in patients with multiple system atrophy: evaluation
      of its relationship with swallowing function.
AB  - BACKGROUND: Vocal fold motion impairment (VFMI), especially vocal fold abductor
      paralysis, is frequently seen in multiple system atrophy (MSA). Since the
      regulation system of laryngeal function is closely related to swallowing
      function, swallowing function is considered to be more involved in MSA patients
      with VFMI than in patients that do not have VFMI. However, the relationship
      between dysphagia and VFMI in MSA patients has not been systematically explored.
      OBJECTIVE: To elucidate the relationship between VFMI and dysphagia in MSA.
      METHODS: We evaluated swallowing function of 36 MSA patients with and without
      VFMI, by videofluoroscopy, and investigated the relationship between VFMI and
      pharyngeal swallowing function. RESULTS: VFMI was found in 17 patients (47.2%).
      Patients with VFMI had advanced severity of the disease. Although there was a
      tendency for bolus stasis at the pyriform sinus and the upper oesophageal
      sphincter opening to be more involved in patients with VFMI, statistical analysis
      did not show significant differences in swallowing function of MSA patients
      between with and without VFMI. In contrast, patients who underwent a tracheotomy
      ultimately required tube feeding or a laryngectomy. CONCLUSIONS: Appearance of
      VFMI is a sign of disease progression but does not necessary mean patients should
      change their way of taking nutrition. However, MSA patients who need a
      tracheotomy might have advanced to a high-risk group for dysphagia. Appropriate
      evaluation and treatment for VFMI and dysphagia are required to maintain
      patients' quality of life in MSA.

PMID- 12810800
TI  - Influence of age on the association between primary hemifacial spasm and arterial
      hypertension.
AB  - OBJECTIVE: To investigate the association between primary hemifacial spasm and
      arterial hypertension. SUBJECTS: 114 patients with primary hemifacial spasm and
      228 neurological controls, matched for age, sex, and referral centre, were
      recruited during an 18 month period from consecutive outpatients attending two
      neurological institutions. DESIGN: The association between exposure variables and
      case/control status was examined in conditional logistic regression models,
      adjusting simultaneously for disease duration and education level. RESULTS:
      Hypertension was more common among the patients with primary hemifacial spasm
      than among the controls. The association was independent of age, disease
      duration, years of schooling, and other diseases (adjusted odds ratio (OR) 2.76
      (95% confidence interval (CI), 1.43 to 5.33); p = 0.002). Hypertension was
      associated with hemifacial spasm in both the left sided group (adjusted OR, 2.76
      (1.18 to 6.44); p = 0.02) and the right sided group (adjusted OR, 3.02 (1.13 to
      8.1); p = 0.03). The association of hypertension with hemifacial spasm was
      apparently greater in the age group < 60 years (adjusted OR, 4.2 (1.4 to 12); p =
      0.008) than in the age group >/= 60 years (adjusted OR, 2.5 (CI 1.3 to 4.6); p =
      0.005), but the difference in the OR estimates between the two age groups was not
      significant. Among hypertensive patients, mean age at the diagnosis of
      hypertension was significantly lower than mean age at the onset of hemifacial
      spasm in the age group >/= 60 years, but not significantly different in the age
      group < 60 years. CONCLUSIONS: The findings support the hypothesised association
      of primary hemifacial spasm with hypertension and raise the possibility that a
      different mechanism underlies the association in different age groups.

PMID- 12810802
TI  - The effect of transcranial magnetic stimulation on movement selection.
AB  - OBJECTIVE: To attempt to replicate previous findings that showed an influence of
      transcranial magnetic stimulation of the cortical motor areas on the selection of
      motor programmes on the contralateral side. METHODS: Healthy volunteers were
      asked to choose to make a right or left index finger extension movement freely
      after hearing the click produced by transcranial magnetic stimulation. The
      stimulation was applied to the motor areas (test), including the motor cortex,
      vertex, and prefrontal cortex, and in the air (control). RESULTS: There was no
      preference for choosing the hand contralateral to the stimulation site, in either
      test or control trials. CONCLUSIONS: Previous results could not be reproduced.
      Simple magnetic stimulation of the motor areas is insufficient to affect
      voluntary selection of movement.

PMID- 12810803
TI  - Informed consent in trials for neurological emergencies: the example of
      subarachnoid haemorrhage.
AB  - BACKGROUND: In patients with acute life threatening diseases, and in their
      relatives, the ability to make a balanced decision on participation in a clinical
      trial may be impaired. OBJECTIVES: To assess what relevant information could be
      recalled by patients who were living independently after a subarachnoid
      haemorrhage, and by their relatives; and to determine how these patients and
      relatives had reacted to the informed consent encounter. METHODS: Twenty months
      (range 7 to 31) after treatment for subarachnoid haemorrhage, 49 patients and 47
      relatives who had participated in one of two randomised trials on medical
      management were interviewed. The interview consisted of items on: spontaneous
      recall and knowledge of trial design; understanding of the trial design and the
      informed consent procedure; the amount and clarity of the information given; and
      reasons for participating. Finally patients and relatives were asked whether they
      would participate again in similar circumstances. RESULTS: One third of the
      patients recalled having participated in a clinical trial. Thirteen per cent of
      the patients and 20% of the relatives felt that the information supplied had not
      been sufficient. Nine per cent of the patients and half the relatives had read
      the written information. None of the patients and one relative thought that
      participation had been obligatory. Twenty eight per cent of the patients and 94%
      of the relatives felt in retrospect that they had been capable of making an
      adequate decision. Virtually all patients and relatives would participate again
      in similar circumstances. CONCLUSIONS: Many patients and their relatives have
      little recall of the informed consent procedure and the essentials of acute
      subarachnoid haemorrhage trials. However, most were satisfied with the overall
      procedure and would participate again.

PMID- 12810804
TI  - Brain stem and cerebellar dysfunction after lumbar spinal fluid drainage: case
      report.
AB  - Lumbar spinal fluid drainage is a common procedure to reduce the risks of
      cerebrospinal fluid (CSF) fistula after skull base fractures or various
      transdural neurosurgical procedures. Nevertheless, this simple and effective
      technique can lead to overdrainage and CSF hypovolaemia. This report describes
      the case of a young patient who had a lumbar drain inserted, to avoid CSF fistula
      after a pterional craniotomy with opening of the frontal sinus for the clipping
      of a ruptured aneurysm. The drain was removed after 48 hours because of
      underdrainage (<1 ml/h). Three days after drain removal, she developed rapid
      deterioration of her level of consciousness and signs of cranial nerves
      involvement, brain stem and cerebellar dysfunction. Intracranial pressure was low
      (<5 cm H(2)O) and MRI showed brain sagging and cerebellar foramen magnum
      herniation. The patient was successfully treated with epidural blood patch,
      ventricular drainage, and Trendelenburg position. The authors report this case
      because CSF hypovolaemia attributable to lumbar overdrainage is an insidious and
      threatening condition not easy to diagnose in the absence of detectable CSF leak.
      MRI and intracranial pressure monitoring confirm the diagnosis and permit better
      understanding of the physiopathology of brain sagging.

PMID- 12810805
TI  - Prolonged survival in motor neuron disease: a descriptive study of the King's
      database 1990-2002.
AB  - Motor neuron disease is a clinically heterogeneous disease with significant
      differences in survival. The authors have characterised a subset of long term
      survivors seen in a tertiary clinic over a 12 year period in terms of clinical
      variables and demographics, comparing them with short term survivors and the
      remaining population. Thirty of 769 patients survived more than 10 years,
      corresponding to 4% of the total population. Significantly younger onset of
      disease symptoms and a predominance of pure upper motor neuron signs at
      presentation characterised the long term survivors, but factors traditionally
      regarded as being associated with poor prognosis were also well represented. For
      a few people with motor neuron disease there remains the hope, whatever the
      initial presentation, that their subsequent survival will be longer than
      expected.

PMID- 12810806
TI  - Autoantibodies to glutamic acid decarboxylase in downbeat nystagmus.
AB  - The cause of downbeat nystagmus (DBN) remains undiagnosed in about 40% of
      patients. This paper reports the presence of antiglutamic acid decarboxylase
      antibodies (GAD-Ab) in a patient with DBN. Antibodies against GABAergic neurons
      located in the vestibular complex may induce chemical denervation of the
      floccular neurons, which normally suppress the peripheral imbalance between
      vertical semicircular canal systems, thereby causing DBN. Testing for GAD-Ab may
      be indicated in DBN patients without an identifiable anatomical brain lesion.

PMID- 12810807
TI  - Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in
      a patient with a brain abscess caused by small colony variants.
AB  - A 45 year old man was admitted to hospital with a right sided facial paralysis
      and three month history of seizures. Computed tomography showed a left temporal
      mass including both intracerebral and extracerebral structures. Ten years earlier
      the patient had undergone a neurosurgical intervention in the same anatomical
      region to treat a subarachnoid haemorrhage. In tissue samples and pus obtained
      during neurosurgery, Staphylococcus aureus was detected by a 16S rRNA-directed in
      situ hybridisation technique. Following long term cultivation, small colony
      variants (SCV) of methicillin resistant S aureus were identified. The patient was
      treated successfully with a combination of vancomycin and rifampin followed by
      prolonged treatment with teicoplanin, with no sign of infection on follow up nine
      months after discharge. This is the first report in which S aureus SCV have been
      identified as causative organisms in a patient with brain abscess and in which in
      situ hybridisation has been used to detect S aureus in a clinical specimen
      containing SCV. Antimicrobial agents such as rifampin which have intracellular
      activity should be included in treatment of infections caused by S aureus SCV.

PMID- 12810808
TI  - Regional cerebral glucose metabolism in akinetic catatonia and after remission.

PMID- 12810809
TI  - Mirth and laughter arising from human temporal cortex.

PMID- 12810810
TI  - How valid is the clinical diagnosis of Parkinson's disease in the community?

PMID- 12810811
TI  - Smoking and cognitive change from age 11 to age 80.

PMID- 12810812
TI  - Organisation of the sympathetic skin response in spinal cord injury.

PMID- 12810813
TI  - Reversible dementias.

PMID- 12810814
TI  - Neuropathology of Hashimoto's encephalopathy.

PMID- 12810815
TI  - Quantitative analysis of fatty acid precursors in marine samples: direct
      conversion of wax ester alcohols and dimethylacetals to FAMEs.
AB  - To apply fatty acid analyses to the study of foraging ecology and diet
      determination, all compounds that may be deposited as fatty acids in a predator
      must be quantified in the prey. These compounds include the usual fatty acids in
      acyl lipids, but also the alcohols of wax esters and the vinyl ethers of
      plasmalogens. In routine fatty acid analysis, samples are extracted and
      transesterified (methylated), resulting in the formation of fatty acid methyl
      esters (FAMEs); however, fatty alcohols and dimethylacetals (DMAs) are also
      generated if wax esters or plasmalogens are present. Here, we present a new
      method using a modified Jones' reagent to oxidize these alcohols and DMAs to free
      fatty acids (FFAs). These FFAs are then easily methylated and quantitatively
      recombined with FAMEs from the same sample. This generates a fatty acid signature
      of prey that is equivalent to that which the predator has available for
      deposition upon digestion of that prey. This method is validated with alcohol and
      DMA standards. Its application to typical marine samples is also presented,
      demonstrating the change in effective fatty acid signature after inclusion of
      fatty acids derived from wax esters and plasmalogens.

PMID- 12810816
TI  - Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/-
      mice by SC-435.
AB  - Blocking intestinal bile acid absorption by inhibiting the apical sodium
      codependent bile acid transporter (ASBT) is a target for increasing hepatic bile
      acid synthesis and reducing plasma LDL cholesterol. SC-435 was identified as a
      potent inhibitor of ASBT (IC50 = 1.5 nM) in cells transfected with the human ASBT
      gene. Dietary administration of 3 mg/kg to 30 mg/kg SC-435 to apolipoprotein E-/-
      (apoE-/-) mice increased fecal bile acid excretion by >2.5-fold. In vivo
      inhibition of ASBT also resulted in significant increases of hepatic mRNA levels
      for cholesterol 7alpha-hydroxylase and HMG-CoA reductase. Administration of 10
      mg/kg SC-435 for 12 weeks to apoE-/- mice lowered serum total cholesterol by 35%
      and reduced aortic root lesion area by 65%. Treatment of apoE-/- mice also
      resulted in decreased expression of ileal bile acid binding protein and hepatic
      nuclear hormone receptor small heterodimer partner, direct target genes of the
      farnesoid X receptor (FXR), suggesting a possible role of FXR in SC-435
      modulation of cholesterol homeostasis. In dogs, SC-435 treatment reduced serum
      total cholesterol levels by </=12% and, in combination with atorvastatin
      treatment, caused an additional reduction of 25%. These results suggest that
      specific inhibition of ASBT is a novel therapeutic approach for treatment of
      hypercholesterolemia resulting in a decreased risk for atherosclerosis.

PMID- 12810818
TI  - OxLDL induces mitogen-activated protein kinase activation mediated via PI3
      kinase/Akt in vascular smooth muscle cells.
AB  - Oxidized low-density lipoprotein (OxLDL) is a risk factor in atherosclerosis and
      stimulates multiple signaling pathways, including activation of
      phosphatidylinositol 3-kinase (PI3-K)/Akt and p42/p44 mitogen-activated protein
      kinase (MAPK), which are involved in mitogenesis of vascular smooth muscle cells
      (VSMCs). We therefore investigated the relationship between PI3-K/Akt and p42/p44
      MAPK activation and cell proliferation induced by OxLDL. OxLDL stimulated Akt
      phosphorylation in a time- and concentration-dependent manner, as determined by
      Western blot analysis. Phosphorylation of Akt stimulated by OxLDL and epidermal
      growth factor (EGF) was attenuated by inhibitors of PI3-K (wortmannin and
      LY294002) and intracellular Ca2+ chelator (BAPTA/AM) plus EDTA. Pretreatment of
      VSMCs with pertussis toxin, cholera toxin, and forskolin for 24 h also attenuated
      the OxLDL-stimulated Akt phosphorylation. In addition, pretreatment of VSMCs with
      wortmannin or LY294002 inhibited OxLDL-stimulated p42/p44 MAPK phosphorylation
      and [3H]thymidine incorporation. Furthermore, treatment with U0126, an inhibitor
      of MAPK kinase (MEK)1/2, attenuated the p42/p44 MAPK phosphorylation, but had no
      effect on Akt activation in response to OxLDL and EGF. Overexpression of p85-DN
      or Akt-DN mutants attenuated MEK1/2 and p42/p44 MAPK phosphorylation stimulated
      by OxLDL and EGF. These results suggest that the mitogenic effect of OxLDL is, at
      least in part, mediated through activation of PI3-K/Akt/MEK/MAPK pathway in
      VSMCs.

PMID- 12810817
TI  - Localization of the PE methylation pathway and SR-BI to the canalicular membrane:
      evidence for apical PC biosynthesis that may promote biliary excretion of
      phospholipid and cholesterol.
AB  - To better understand the regulation of biliary phospholipid and cholesterol
      excretion, canalicular membranes were isolated from the livers of C57BL/6J mice
      and abundant proteins separated by SDS-PAGE and identified by matrix-assisted
      laser desorption/ionization mass spectrometry. A prominent protein revealed by
      this analysis was betaine homocysteine methyltransferase (BHMT). This enzyme
      catalyzes the first step in a three-enzyme pathway that promotes the methylation
      of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Immunoblotting
      confirmed the presence of BHMT on the canalicular membrane, failed to reveal the
      presence of the second enzyme in this pathway, methionine adenosyltransferase,
      and localized the third enzyme of the pathway, PE N-methyltransferase (PEMT).
      Furthermore, immunfluorescence microscopy unambiguously confirmed the
      localization of PEMT to the canalicular membrane. These findings indicate that a
      local mechanism exists in or around hepatocyte canalicular membranes to promote
      phosphatidylethnolamine methylation and PC biosynthesis. Finally, immunoblotting
      revealed the presence and immunofluorescence microscopy unambiguously localized
      the scavenger receptor class B type I (SR-BI) to the canalicular membrane.
      Therefore, SR-BI, which is known to play a role in cholesterol uptake at the
      hepatocyte basolateral membrane, may also be involved in biliary cholesterol
      excretion. Based on these findings, a model is proposed in which local
      canalicular membrane PC biosynthesis in concert with the phospholipid transporter
      mdr2 and SR-BI, promotes the excretion of phospholipid and cholesterol into the
      bile.

PMID- 12810819
TI  - Calcium-independent phospholipase A2 mediates CREB phosphorylation in double
      stranded RNA-stimulated endothelial cells.
AB  - One of the products of a calcium-independent phospholipase A2 (iPLA2) attack of
      plasmenylcholine, lysoplasmenylcholine, has previously been shown to activate
      cAMP-dependent protein kinase (PKA). Because endothelial cells respond to some
      agonists in part by the activation of iPLA2, the present study was designed to
      determine whether double-stranded RNA (dsRNA), the primary activator of the
      antiviral response in endothelial cells, elicits cAMP response element binding
      protein (CREB) phosphorylation through a mechanism mediated by iPLA2. dsRNA
      stimulated CREB phosphorylation in bovine pulmonary artery endothelial cells that
      was inhibited by the iPLA2 inhibitor, bromoenol lactone, and the PKA inhibitor, H
      89. Additionally, the product of iPLA2 hydrolysis of plasmenylcholine and
      lysoplasmenylcholine elicited CREB phosphorylation in bovine pulmonary
      endothelial cells. Taken together, the present studies suggest that dsRNA as well
      as other agonists of endothelial cells elicit signaling mechanisms that include
      in part CREB phosphorylation mediated by iPLA2.

PMID- 12810820
TI  - PLTP secreted by HepG2 cells resembles the high-activity PLTP form in human
      plasma.
AB  - Plasma phospholipid transfer protein (PLTP) is an important regulator of plasma
      HDL levels and HDL particle distribution. PLTP is present in plasma in two forms,
      one with high and the other with low phospholipid transfer activity. We have used
      the human hepatoma cell line, HepG2, as a model to study PLTP secreted from
      hepatic cells. PLTP activity was secreted by the cells into serum-free culture
      medium as a function of time. However, modification of a previously established
      ELISA assay to include a denaturing sample pretreatment with the anionic
      detergent sodium dodecyl sulphate was required for the detection of the secreted
      PLTP protein. The HepG2 PLTP could be enriched by Heparin-Sepharose affinity
      chromatography and eluted in size-exclusion chromatography at a position
      corresponding to the size of 160 kDa. PLTP coeluted with apolipoprotein E (apoE)
      but not with apoB-100 or apoA-I. A portion of PLTP was retained by an anti-apoE
      immunoaffinity column together with apoE, suggesting an interaction between these
      two proteins. Furthermore, antibodies against apoE but not those against apoB-100
      or apoA-I were capable of inhibiting PLTP activity. These results show that the
      HepG2-derived PLTP resembles in several aspects the high-activity form of PLTP
      found in human plasma.

PMID- 12810821
TI  - Effects of unsaturated fatty acids and triacylglycerols on
      phosphatidylethanolamine membrane structure.
AB  - Lipid intake in diet regulates the membrane lipid composition, which in turn
      controls activities of membrane proteins. There is evidence that fatty acids
      (FAs) and triacylglycerols (TGs) can alter the phospholipid (PL) mesomorphism.
      However, the molecular mechanisms involved are not fully understood. This study
      focuses on the effect of the unsaturation degree of the C-18 FAs, oleic acid
      (OA), linoleic acid and linolenic acid, and their TGs, triolein (TO),
      trilinolein, and trilinolenin, on the structural properties of
      phosphoethanolamine PLs. By means of X-ray diffraction and 31P-NMR spectroscopy,
      it is shown that both types of molecules stabilize the HII phase in 1,2
      dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) liposomes. Several structural
      factors are considered to explain the correlation between the FA unsaturation
      degree and the onset temperature of the HII phase. It is proposed that TGs could
      act as lateral spacers between polar DEPE groups, providing an increase in the
      effective surface area per lipid molecule that would account for the structural
      parameters of the HII phase. Fluorescence polarization data indicated a
      fluidification effect of OA on the lamellar phase. TO increased the viscosity of
      the hydrophobic core with a high effect on the HII phase.

PMID- 12810822
TI  - Seminolipid and its precursor/degradative product, galactosylalkylacylglycerol,
      in the testis of saposin A- and prosaposin-deficient mice.
AB  - Sphingolipid activator proteins (saposins A, B, C, and D) are derived from a
      common precursor protein (prosaposin) and specifically activate in vivo
      degradation of glycolipids with short carbohydrate chains. A mouse model of
      prosaposin deficiency (prosaposin-/-) closely mimics the human disease with an
      elevation of multiple glycolipids. The recently developed saposin A-/- mice
      showed a chronic form of globoid cell leukodystrophy, establishing the essential
      in vivo role of saposin A as an activator for galactosylceramidase to degrade
      galactosylceramide. Seminolipid, the principal glycolipid in spermatozoa, and its
      precursor/degradative product, galactosylalkylacylglycerol (GalEAG), were
      analyzed in the testis of the two mouse mutants by electrospray ionization mass
      spectrometry. Saposin A-/- mice showed the normal seminolipid level, while that
      of prosaposin-/- mice was approximately 150% of the normal level at the terminal
      stage. In contrast, GalEAG increased up to 10 times in saposin A-/- mice, whereas
      it decreased with age in the wild-type as well as in prosaposin-/- mice. These
      analytical findings on the two saposin mutants may shed some light on the
      physiological function of seminolipid and GalEAG.

PMID- 12810823
TI  - Loci controlling plasma non-HDL and HDL cholesterol levels in a C57BL /6J x CASA
      /Rk intercross.
AB  - Plasma non-HDL and HDL cholesterol levels are predictors of cardiovascular
      diseases. We carried out a genetic cross between two laboratory inbred mouse
      strains, C57BL/6J and CASA/Rk, to detect loci that control the plasma levels of
      non-HDL and HDL cholesterol. With regard to non-HDL cholesterol, chow-fed CASA/Rk
      males and females had 87% and 25% higher levels, respectively, than did
      C57BL/6Js. The levels of non-HDL cholesterol in F1s were similar to C57BL/6J.
      There was no strain difference in HDL cholesterol levels. An intercross between
      F1s was performed, and plasma non-HDL and HDL cholesterol was measured in 185
      male and 184 female mice. In both male and female F2 mice, plasma non-HDL and HDL
      cholesterol levels were unimodally distributed; however, in both cases the values
      for females were significantly lower than for males. Therefore, linkage analysis
      was performed with sex as a covariate. Significant linkage for non-HDL
      cholesterol was found on chromosome 6 at 49 cM (LOD 5.17), chromosome 4 at 55 cM
      (LOD 4.22), and chromosome 8 at 7 cM (LOD 3.68). Significant linkage for HDL
      cholesterol was found on chromosome 9 at 14 cM (LOD 7.52) and chromosome 8 at 76
      cM (LOD 4.69). A significant epistatic interaction involving loci on chromosomes
      2 and 5 was also observed for non-HDL cholesterol. In summary, linkage analysis
      in these cross-identified novel loci confirmed previously identified loci in
      control of plasma non-HDL and HDL cholesterol and disclosed a novel interaction
      in controlling non-HDL cholesterol levels in the mouse.

PMID- 12810824
TI  - Sterol carrier protein-2/sterol carrier protein-x expression differentially
      alters fatty acid metabolism in L cell fibroblasts.
AB  - Sterol carrier protein-2 (SCP-2) and SCP-x are ubiquitous proteins found in all
      mammalian tissues. Although both proteins interact with fatty acids, their
      relative contributions to the uptake, oxidation, and esterification of straight
      chain (palmitic) and branched-chain (phytanic) fatty acids in living cells has
      not been resolved. Therefore, the effects of each gene product on fatty acid
      metabolism was individually examined. Based on the following, SCP-2 and SCP-x did
      not enhance the uptake/translocation of fatty acids across the plasma membrane
      into the cell: i) a 2-fold increase in phytanic and palmitic acid uptake was
      observed at long incubation times in SCP-2- and SCP-x-expressing cells, but no
      differences were observed at initial time points; ii) uptake of 2-bromo
      palmitate, a nonoxidizable, poorly metabolizable fatty acid analog, was
      unaffected by SCP-2 or SCP-x overexpression; and iii) SCP-2 and SCP-x expression
      did not increase targeting of radiolabeled phytanic and palmitic acid to the
      unesterified fatty acid pool. Moreover, SCP-2 and SCP-x expression enhanced fatty
      acid uptake by stimulating the intracellular metabolism via fatty acid oxidation
      and esterification. In summary, these data showed for the first time that SCP-2
      and SCP-x stimulate oxidation and esterification of branched-chain as well as
      straight-chain fatty acids in intact cells.

PMID- 12810825
TI  - Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and
      DBA/2J inbred mouse strains.
AB  - A complex genetic basis determines the individual predisposition to develop
      cholesterol gallstones in response to environmental factors. We employed
      quantitative trait locus/loci (QTL) analyses of an intercross between inbred
      strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of
      gallstone susceptibility (Lith) genes these strains possess. Parental and first
      filial generation mice of both genders and male intercross offspring were
      evaluated for gallstone formation after feeding a lithogenic diet. Linkage
      analysis was performed using a form of multiple interval mapping. One significant
      QTL colocalized with Lith1 [chromosome (chr) 2, 50 cM], a locus identified
      previously. Significantly, new QTL were detected and named Lith10 (chr 6, 4 cM),
      Lith6 (chr 6, 54 cM), and Lith11 (chr 8, 58 cM). Statistical and genetic analyses
      suggest that Lith6 comprises two QTL in close proximity. Our molecular and
      genetic data support the candidacy of peroxisome proliferator-activated receptor
      gamma (Pparg) and Slc21a1, encoding Pparg, and the basolateral bile acid
      transporter SLC21A1 (Slc21a1/Oatp1), respectively, as genes underlying Lith6.

PMID- 12810826
TI  - Physicochemical and physiological properties of 5alpha-cyprinol sulfate, the
      toxic bile salt of cyprinid fish.
AB  - 5alpha-Cyprinol sulfate was isolated from bile of the Asiatic carp, Cyprinus
      carpio. 5alpha-Cyprinol sulfate was surface active and formed micelles; its
      critical micellization concentration (CMC) in 0.15 M Na+ using the maximum bubble
      pressure device was 1.5 mM; by dye solubilization, its CMC was approximately 4
      mM. At concentrations >1 mM, 5alpha-cyprinol sulfate solubilized
      monooleylglycerol efficiently (2.1 molecules per mol micellar bile salt). When
      infused intravenously into the anesthetized rat, 5alpha-cyprinol sulfate was
      hemolytic, cholestatic, and toxic. In the isolated rat liver, it underwent little
      biotransformation and was poorly transported (Tmax congruent with 0.5
      micromol/min/kg) as compared with taurocholate. 5alpha-Cyprinol, its bile alcohol
      moiety, was oxidized to its corresponding C27 bile acid and to allocholic acid
      (the latter was then conjugated with taurine); these metabolites were efficiently
      transported. 5alpha-Cyprinol sulfate inhibited taurocholate uptake in COS-7 cells
      transfected with rat asbt, the apical bile salt transporter of the ileal
      enterocyte. 5alpha-Cyprinol had limited aqueous solubility (0.3 mM) and was
      poorly absorbed from the perfused rat jejunum or ileum. Sampling of carp
      intestinal content indicated that 5alpha-cyprinol sulfate was present at micellar
      concentrations, and that it did not undergo hydrolysis during intestinal transit.
      These studies indicate that 5alpha-cyprinol sulfate is an excellent digestive
      detergent and suggest that a micellar phase is present during digestion in
      cyprinid fish.

PMID- 12810827
TI  - Quantitation of two pathways for cholesterol excretion from the brain in normal
      mice and mice with neurodegeneration.
AB  - Although the pool of cholesterol in the adult central nervous system (CNS) is
      large and of constant size, little is known of the process(es) involved in
      regulation of sterol turnover in this pool. In 7-week-old mice, net excretion of
      cholesterol from the brain equaled 1.4 mg/day/kg body weight, and from the whole
      animal was 179 mg/day/kg. Deletion of cholesterol 24-hydroxylase, an enzyme
      highly expressed in the CNS, did not alter brain growth or myelination, but
      reduced sterol excretion from the CNS 64% to 0.5 mg/day/kg. In mice with a
      mutation in the Niemann-Pick C gene that had ongoing neurodegeneration, sterol
      excretion from the CNS was increased to 2.3 mg/day/kg. Deletion of cholesterol 24
      hydroxylase activity in these animals reduced net excretion only 22% to 1.8
      mg/day/kg. Thus, at least two different pathways promote net sterol excretion
      from the CNS. One uses cholesterol 24-hydroxylase and may reflect sterol turnover
      in large neurons in the brain. The other probably involves the movement of
      cholesterol or one of its metabolites across the blood-brain barrier and may more
      closely mirror sterol turnover in pools such as glial cell membranes and myelin.

PMID- 12810828
TI  - Molecular mechanisms of myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a family of clonal disorders of hematopoietic
      stem cells that are characterized by ineffective hematopoiesis and susceptibility
      to acute myelogenous leukemias and are shown to be strikingly refractory to
      current therapeutic modalities. A substantial proportion of these complex
      diseases arises in the setting of exposures to environmental or occupational
      toxins, including cytotoxic therapy for a prior malignancy or other disorder. The
      conversion of a normal stem cell into a preleukemic and ultimately leukemic state
      is a multistep process requiring the accumulation of a number of genetic lesions.
      At the genomic level, MDS is typified by losses and translocations involving
      certain key gene segments, with disruption of the normal structure and function
      of genes that control the balance of proliferation and differentiation of
      hematopoietic precursors. More than half of the chromosomal abnormalities in MDS
      comprise deletions of chromosomes 5, 7, 11, 12, 13 and 20. This evidence suggests
      that as yet unidentified tumor-suppressor genes should have important roles in
      the molecular mechanisms of MDS. Further molecular approaches to such genetic
      lesions will identify the relevant tumor-suppressor genes. Over the past years,
      major signal transduction molecules have been identified and their genetic
      alterations have been extensively analyzed in both MDS and leukemias. These
      include receptors for growth factors, RAS signaling molecules, cell cycle
      regulators and transcription factors. Notable among them are transcription
      factors that regulate both proliferation and differentiation of hematopoietic
      stem cells. The disruption of the normal flow of the signal transduction pathways
      involving these molecules translates into ineffective multilineage hematopoiesis
      and bone marrow failure. Therefore, MDS provides a fertile testing ground on
      which we could study the molecular dissection implicated in the multistep
      leukemogenesis.

PMID- 12810829
TI  - Pathological assessment of intraductal spread of carcinoma in relation to
      surgical margin state in breast-conserving surgery.
AB  - BACKGROUND: Spreading of carcinoma has been considered to be a prognostic factor
      for local failure after breast-conserving therapy. The extensive intraductal
      component (EIC) was defined as when the component of intraductal carcinoma
      constitutes more than 25% of the primary tumor with intraductal foci. However,
      the definition of EIC was based on the predominance of intraductal component
      surrounding the invasive lesions and not on the segmental anatomy. We designated
      carcinoma extension as the intraductal spread of carcinoma (ISC) along with the
      duct-lobular system by three-dimensional (3-D) reconstruction analysis. This
      study was initiated to simplify the method of two-dimensional (2-D) pathological
      examination based on 3-D mapping. METHODS: Thirty-four specimens from breast
      cancer patients were subjected to 3-D reconstruction. We investigated the
      correlation between actual extension of intraductal carcinoma and EIC defined by
      2-D examination or ISC grading defined by 3-D reconstruction. Furthermore, using
      another 62 histological mappings, we investigated how correctly the simplified 2
      D method using several paraffin blocks reflected the actual carcinoma spread and
      margin state. RESULTS: Carcinoma extension over 2 cm was observed in 64%
      specimens that were EIC positive and 26% specimens that were EIC negative. In
      contrast, according to the ISC grading defined by 3-D reconstruction, none of the
      specimens with a low grade of ISC demonstrated carcinoma extension over 2 cm.
      Carcinoma extension over 2 cm was observed in 71% of specimens with a high grade
      of ISC, thus demonstrating a correlation between carcinoma extension and ISC
      grading. In addition, the simplified 2-D method using only several blocks
      reflected both the 3-D ISC grading and surgical margin state. CONCLUSIONS: We
      conclude that ISC grading correlates with carcinoma extension and surgical margin
      state. From a clinical point of view, the simplified 2-D examination using
      paraffin blocks may contribute to routine surgical pathology in evaluating the
      degree of carcinoma extension in breast-conserving therapy.

PMID- 12810830
TI  - Clinical significance of bone marrow micrometastasis detected by nested rt-PCR
      for keratin-19 in breast cancer patients.
AB  - PURPOSE: Breast cancers in the early phase frequently undergo distant metastasis
      and survival of patients is greatly dependent on distant metastasis. The
      occurrence of micrometastasis has been suggested to relate with prognostic
      features of breast cancer, such as lymph node metastasis and the presence of
      vascular invasion. The aim of this study was to examine the presence of keratin
      19 mRNA of epithelial tumors in bone marrow aspirates obtained from breast cancer
      patients and its possible correlation with tumor staging and disease-free
      survival. METHODS: Bone marrow samples were obtained from 59 breast cancer
      patients at the time of surgery. We separated the mononuclear fraction from the
      samples and carried out nested reverse transcriptase polymerase chain reaction
      (RT-PCR) for the detection of keratin-19 mRNA with two different pairs of
      primers. After operation, the patients were followed up at 3-month intervals. We
      studied the possible correlation of the detection of keratin-19 mRNA with tumor
      size, nodal involvement, stage and recurrence rate. RESULTS: Bone marrow
      micrometastasis was detected by nested RT-PCR for keratin-19 mRNA in one of four
      patients with ductal carcinoma in situ (DCIS), 13 of 30 patients with T1, 11 of
      20 patients with T2 and all four patients with T3 lesion. Recurrence was observed
      in seven cases and all of them were positive for micrometastasis in bone marrow.
      CONCLUSION: The method of nested RT-PCR to detect the presence of keratin-19 mRNA
      in bone marrow from patients with breast cancer is sensitive and reliable.
      Moreover, early recurrence was observed in the patients with the tumor mRNA
      detected in bone marrow. Additional studies with larger numbers of patients and
      longer follow-up are desirable.

PMID- 12810831
TI  - Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer.
AB  - BACKGROUND: Although the TNM stage is the most important prognostic factor for
      gastric cancer, there is a need for new prognostic and predictive factors,
      because the prognosis varies among patients of the same stage. The purpose of
      this study was to clarify the relationship of p53, nm23, proliferating cell
      nuclear antigen (PCNA) and c-erbB-2 with the clinicopathological parameters and
      the survival results. METHODS: For 841 patients who had undergone gastrectomy for
      gastric cancer at Seoul National University Hospital from July 1996 to December
      1997, the expression levels of p53, nm23, PCNA and c-erbB-2 in gastric cancer
      tissues were examined immunohistochemically. Also, the clinicopathological
      parameters such as gender, age, operation type, TNM stage and size of the tumor,
      histology and Lauren classification were analyzed retrospectively. RESULTS: There
      were 568 males and 273 females (2.07:1) with a mean age of 56 years (range:25-82
      years). The percentages of positive expression of p53, nm23 and c-erbB-2 were 43,
      74 and 17%, respectively; 59% of tumors expressed PCNA index > or =50. p53
      expression was associated with age, gender, tumor size, histology, Lauren
      classification, stage, nm23 expression, PCNA index >or =50 and c-erbB-2
      expression. nm23 expression was associated with age, tumor size, Borrmann type,
      histology, Lauren classification and stage. PCNA index > or =50 was associated
      with age, gender, tumor size, Borrmann type, histology, Lauren classification and
      c-erbB-2 expression. c-erbB-2 expression was associated with gender, Borrmann
      type, histology and Lauren classification. p53 and nm23 were related with poor
      prognosis in univariate analysis. nm23 was related with poor prognosis of stage
      III and diffuse-type gastric cancer in univariate subgroup analysis. However, in
      a multivariate study, these prognostic impacts were not maintained. CONCLUSION:
      The expression of p53 and nm23 seems to be related with poor prognosis of gastric
      cancer patients who have undergone gastrectomy. However, the prognostic
      significance was not revealed by a multivariate analysis.

PMID- 12810832
TI  - Efficacy of chemoradiotherapy on pain relief in patients with intrapelvic
      recurrence of rectal cancer.
AB  - PURPOSE: To assess the efficacy of chemoradiotherapy on pain relief in patients
      with intrapelvic recurrence of rectal cancer. METHODS: The records of 30 patients
      treated with radiotherapy with or without chemotherapy for intrapelvic recurrence
      of rectal cancer between September 1993 and February 1999 were retrospectively
      reviewed. There were 17 patients in the chemoradiotherapy (CRT) group and 13
      patients in the radiotherapy alone (RTA) group. Simultaneous extrapelvic distant
      metastases were found in 11 patients in the CRT group and in seven patients in
      the RTA group. Radiotherapy was administered with a median total dose of 50 Gy in
      both groups. In the CRT group, 15 patients received 5-fluorouracil by continuous
      infusion and two patients received irinotecan in a biweekly infusion schedule
      during the course of radiotherapy. The response rate and duration of pain relief
      were evaluated and were compared between the two groups. RESULTS: The response
      rate of pain relief in the CRT and RTA was 100 and 77%, respectively. The median
      duration of pain relief in the CRT and RTA groups was 7.8 and 4.0 months,
      respectively and there was a significant difference between the two groups (P =
      0.019). The median survival time from the start of radiotherapy was 15.1 and 9.3
      months in the CRT and RTA groups, respectively, and there was a significant
      difference between the two groups (P = 0.046). CONCLUSIONS: The results suggest
      that chemoradiotherapy for intrapelvic recurrence of rectal cancer for the
      purpose of pain relief appears to be more effective than radiotherapy alone.

PMID- 12810833
TI  - Determining the levels of matrix metalloproteinase-9 in portal and peripheral
      blood is useful for predicting liver metastasis of colorectal cancer.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is one of the MMPs that play an
      important role in cancer invasion and metastasis. Increased levels of MMP-9 in
      tumor tissue have been found to correlate with advanced stages of colorectal
      cancer. However, the clinical significance of determining the levels of MMP-9 in
      blood samples from patients with colorectal cancer has not yet been clarified.
      The purpose of this study was to clarify the relationship between the
      clinicopathological variables of colorectal cancer and MMP-9 levels of drainage
      (portal) or peripheral venous blood and to examine whether this assay would be
      useful for predicting liver metastasis. METHODS: Blood samples were obtained from
      peripheral and drainage veins of 102 patients with colorectal cancer during
      surgery and the plasma levels of MMP-9 were determined by a one-step sandwich
      enzyme immunoassay. RESULTS: The levels of portal MMP-9 were significantly higher
      than those of peripheral blood (P < 0.01, n = 102). The levels of MMP-9 in
      peripheral venous blood did not correlate with any of the 12 clinicopathological
      variables examined, while the levels of MMP-9 in portal blood correlated with
      macroscopic type of the primary tumor (P = 0.02), Dukes' stage (P = 0.03), liver
      metastasis (P < 0.01) and lymph node metastasis (P = 0.02). By setting the cutoff
      ratio of portal to peripheral MMP-9 levels at 1.6 in patients with curative
      resection (n = 73), elevated ratios predicted subsequent emergence of liver
      metastases with 77.8% sensitivity, 81.3% specificity and 80.8% accuracy.
      CONCLUSION: The results suggest that synchronous determination of the levels of
      MMP-9 in portal and peripheral blood would be useful for selecting colorectal
      cancer patients at high risk of hepatic recurrence.

PMID- 12810834
TI  - Helicobacter pylori seropositivity and the myeloperoxidase G-463A polymorphism in
      combination with interleukin-1B C-31T in Japanese health checkup examinees.
AB  - OBJECTIVE: Genetic susceptibility appears to play an important role in
      Helicobacter pylori (HP) infection. The present study was conducted to re-examine
      the reported association between the myeloperoxidase (MPO) G-463A polymorphism
      and HP seropositivity in different subjects and to investigate interactions with
      smoking behavior and the interleukin-1B (IL-1B) C-31T polymorphism. METHODS: The
      subjects were 468 health checkup examinees in Nagoya, who consented to anonymous
      genotyping of residual blood samples. Genotyping was conducted by PCR-RFLP for
      MPO G-463A and PCR-CTPP for IL-1B C-31T. RESULTS: Among the successfully
      genotyped 437 participants without a cancer history, the HP seropositive rate was
      56.2% for -463GG (n = 354), 49.4% for -463GA (n = 77) and 83.3% for -463AA (n =
      6). The gender-age-adjusted odds ratio (aOR) for GA/AA relative to GG was 0.86
      (95% confidence interval, 0.32-1.34) among males, 0.84 (0.47-1.49) among females,
      0.83 (0.22-3.05) among current smokers and 0.87 (0.50-1.51) among never smokers.
      Analysis by IL-1B C-31T genotype revealed a significantly reduced OR of 0.41
      (0.18-0.93) among the participants with IL-1B -31CT. The OR for IL-1B -31TT
      relative to -31CC/CT was 1.59 (1.00-2.55) among those with MPO -463GG and 3.36
      (1.16-9.77) with MPO -463GA/AA. None of the gene-environment or gene-gene
      interactions proved to be statistically significant. CONCLUSIONS: The association
      between MPO G-463A and HP seropositivity was not reproduced in this study. The
      effect of IL-1B -31TT was more prominent among individuals with the low
      expression MPO -463A allele, but it remains to be confirmed for other datasets.

PMID- 12810835
TI  - Iridium-192 brachytherapy for hemorrhagic angiosarcoma of the scalp: a case
      report.
AB  - A 60-year-old woman presented with multicentric skin tumors of the head. The
      histologically proven hemangioendothelioma was bleeding as a result of
      disseminated coagulopathy. In addition to immunotherapy, 6 MeV electron beam
      radiotherapy was used for the purpose of hemostasis with a single portal, 20 x 20
      cm in size, covering the whole scalp from the top of the head. The radiotherapy
      was discontinued after 39 Gy/13 fractions/20 days because of the progress in size
      of a peripheral tumor and the stability of coagulopathy. After another electron
      boost delivery by two portals focused to exophytic parietal and temporal tumors
      of 20 Gy/10 fractions, high dose rate brachytherapy with a surface mold technique
      was performed, 3 Gy/fraction, four fractions/week, for a total of 36 Gy. It
      induced partial regression of the tumor and complete recovery of platelet counts
      from 2.5 x 10(4) to 18.2 x 10(4). The tumor disappeared in 3 months. No late side
      effects occurred, except for permanent alopecia. The patient developed a cervical
      lymph node metastasis 1 year after and marginal recurrence 2 years after the
      initial treatment. Both recurrent tumors were successfully treated by 4 MV
      external photons of 60 Gy/20 fractions/46 days and electron beam irradiation of
      60 Gy/20 fractions/29 days, respectively. She has remained disease free for 3
      years after the initial presentation.

PMID- 12810836
TI  - Aging of skeletal muscle does not affect the response of satellite cells to
      denervation.
AB  - Satellite cells (SCs) are the main source of new fibers in regenerating skeletal
      muscles and the key contributor to extra nuclei in growing fibers during
      postnatal development. Aging results in depletion of the SC population and in the
      reduction of its proliferative activity. Although it has been previously
      determined that under conditions of massive fiber death in vivo the regenerative
      potential of SCs is not impaired in old muscle, no studies have yet tested
      whether advanced age is a factor that may restrain the response of SCs to muscle
      denervation. The present study is designed to answer this question, comparing the
      changes of SC numbers in tibialis anterior (TA) muscles from young (4 months) and
      old (24 months) WI/HicksCar rats after 2 months of denervation. Immunostaining
      with antibodies against M-cadherin and NCAM was used to detect and count the SCs.
      The results demonstrate that the percentages of both M-cadherin- and NCAM
      positive SCs (SC/Fibers x 100) in control TA muscles from young rats (5.6 +/-
      0.5% and 1.4 +/- 0.2%, respectively) are larger than those in old rats (2.3 +/-
      0.3% and 0.5 +/- 0.1%, respectively). At the same time, in 2-month denervated TA
      muscles the percentages of M-cadherin and NCAM positive SC are increased and
      reach a level that is comparable between young (16.2 +/- 0.9% and 7.5 +/- 0.5%,
      respectively) and old (15.9 +/- 0.7% and 10.1 +/- 0.5%, respectively) rats. Based
      on these data, we suggest that aging does not repress the capacity of SC to
      become activated and grow in the response to muscle denervation.

PMID- 12810838
TI  - Comparison of comet assay, electron microscopy, and flow cytometry for detection
      of apoptosis.
AB  - Differentiating apoptosis from necrosis is a challenge in single cells and in
      parenchymal tissues. The techniques available, including in situ TUNEL (Terminal
      deoxyribonucleotide transferase-mediated dUTP-X Nick End-Labeling) staining, DNA
      ladder assay, and flow cytometry, suffer from low sensitivity or from a high
      false-positive rate. This study, using a Jurkat cell model, initially evaluated
      the specificity of the neutral comet assay and flow cytometry compared to the
      gold standard, electron microscopy, for detection of apoptosis and necrosis.
      Neutral comet assay distinguished apoptosis from necrosis in Jurkat cells, as
      evidenced by the increased comet score in apoptotic cells and the almost zero
      comet score in necrotic cells. These findings were consistent with those of
      electron microscopy and flow cytometry. Furthermore, using rats with burn or
      ischemia/reperfusion injury, well-established models of skeletal and cardiac
      muscle tissue apoptosis, respectively, we applied the comet assay to detect
      apoptosis in these muscles. Neutral comet assay was able to detect apoptotic
      changes in both models. In the muscle samples from rats with burn or ischemia
      reperfusion injury, the comet score was higher than that of muscle samples from
      their respective controls. These studies confirm the consistency of the comet
      assay for detection of apoptosis in single cells and provide evidence for its
      applicability as an additional method to detect apoptosis in parenchymal cells.

PMID- 12810837
TI  - Quantitative histochemical assay for superoxide dismutase in rat brain.
AB  - Superoxide anions are highly reactive radicals overproduced in many pathological
      situations such as inflammation and ischemia. One of the major factors in the
      protection from superoxide anions is the enzyme superoxide dismutase (SOD), which
      catalyzes the dismutation of superoxide to hydrogen peroxide. This study presents
      a quantitative histochemical method to estimate SOD activity in rat brain tissue
      sections. This method is based on the cerium capture method and 3,3'
      diaminobenzidine amplification of transition cerium compounds. Substrate for SOD
      was provided by reduction of oxygen during the autoxidation of riboflavin in the
      presence of UV light. This histochemical method reveals the overall activity of
      the three different forms of SOD described in mammalian tissues: cytosolic copper
      zinc SOD, mitochondrial manganese SOD, and the high molecular weight
      extracellular SOD. Eventually, this method can be used to quantify SOD activity
      in tissue sections by image analysis.

PMID- 12810839
TI  - The distribution of Abcc6 in normal mouse tissues suggests multiple functions for
      this ABC transporter.
AB  - We have studied the tissue distribution of Abcc6, a member of the ABC
      transmembrane transporter subfamily C, in normal C57BL/6 mice. RNase protection
      assays revealed that although almost all tissues studied contained detectable
      levels of the mRNA encoding Abcc6, the highest levels of Abcc6 mRNA were found in
      the liver. In situ hybridization (ISH) demonstrated abundant Abcc6 mRNA in
      epithelial cells from a variety of tissues, including hepatic parenchymal cells,
      bile duct epithelia, kidney proximal tubules, mucosa and gland cells of the
      stomach, intestine, and colon, squamous epithelium of the tongue, corneal
      epithelium of the eye, keratinocytes of the skin, and tracheal and bronchial
      epithelium. Furthermore, we detected Abcc6 mRNA in arterial endothelial cells,
      smooth muscle cells of the aorta and myocardium, in circulating leukocytes,
      lymphocytes in the thymus and lymph nodes, and in neurons of the brain, spinal
      cord, and the specialized neurons of the retina. Immunohistochemical analysis
      using a polyclonal Abcc6 rabbit antibody confirmed the tissue distribution of
      Abcc6 suggested by our ISH studies and revealed the cellular localization of
      Abcc6 in the basolateral plasma membrane in the epithelial cells of proximal
      convoluted tubules in the kidney. Although the function of Abcc6 is unknown,
      mutations in the human ABCC6 gene result in a heritable disorder of connective
      tissue called pseudoxanthoma elasticum (PXE). Our results demonstrating the
      presence of Abcc6 in epithelial and endothelial cells in a variety of tissues,
      including those tissues affected in PXE patients, suggest a possible role for
      Abcc6 in the normal assembly of extracellular matrix components. However, the
      presence of Abcc6 in neurons and leukocytes, two cell populations not associated
      with connective tissue, also suggests a more complex multifunctional role for
      Abcc6.

PMID- 12810840
TI  - Expression of gap junction protein connexin43 in the adult rat cochlea:
      comparison with connexin26.
AB  - To elucidate whether the two different gap junction proteins connexin43 (Cx43)
      and connexin26 (Cx26) are expressed and localized in a similar manner in the
      adult rat cochlea, we performed three-dimensional confocal microscopy using
      cryosections and surface preparations. In the cochlear lateral wall, Cx43
      positive spots were localized mainly in the stria vascularis and only a few spots
      were present in the spiral ligament, whereas Cx26-positive spots were detected in
      both the stria vascularis and the spiral ligament. In the spiral limbus, Cx43 was
      widely distributed, whereas Cx26 was more concentrated on the side facing the
      scala vestibuli and in the basal portion. In the organ of Corti, Cx43-positive
      spots were present between the supporting cells but they were fewer and much
      smaller than those of Cx26. These data demonstrated distinct differences between
      Cx43 and Cx26 in expression and localization in the cochlea. In addition, the
      area of overlap of zonula occludens-1 (ZO-1) immunolabeling with Cx43-positive
      spots was small, whereas it was fairly large with Cx26-positive spots in the
      cochlear lateral wall, suggesting that the differences are not associated with
      the structural difference between carboxyl terminals, i.e., those of Cx43 possess
      sequences for binding to ZO-1, whereas those of Cx26 lack these binding
      sequences.

PMID- 12810841
TI  - Detection of oligodendrocytes in tissue sections using PCR synthesis of
      digoxigenin-labeled probes.
AB  - Oligodendrocytes, the myelin-forming cells in the central nervous system, were
      visualized with excellent resolution at the light microscopic level using in situ
      hybridization (ISH). Digoxigenin (Dig)-tagged probes were synthesized and
      efficiently labeled by PCR. Specific probes to myelin genes were made by RT from
      brain total RNAs, followed by PCR with designed specific primers in the presence
      of Dig-11-dUTP. Probes specific to proteolipid protein (PLP), PLP and its isoform
      DM20 (PLP/DM20), and myelin oligodendrocyte glycoprotein (MOG) were synthesized
      and labeled. ISH was then applied on vibratomed tissue sections from mouse
      brains. Despite a low expression of MOG-specific and PLP-specific mRNAs in adult
      and newborn mouse brains, an oligodendrocyte population was detected. The
      specificity of Dig-labeled probes was confirmed with the double labeling of
      carbonic anhydrase II (CA II) and glial fibrillary acidic protein (GFAP)
      immunocytochemistry and ISH. This versatile and easy method for synthesis and
      labeling of specific probes to oligodendrocytes can be also applied to detect
      many other mRNAs in the nervous system and in other tissues.

PMID- 12810842
TI  - Alterations of collagen XVII expression during transformation of oral epithelium
      to dysplasia and carcinoma.
AB  - Collagen XVII (BP180) is a hemidesmosomal transmembrane component that has been
      hypothesized to participate in keratinocyte adhesion and motility. Using
      immunohistochemical (IHC) and in situ hybridization (ISH) methods, we showed
      downregulation of collagen XVII in basal cells in mild dysplasias and
      upregulation in suprabasal keratinocytes in moderate and severe dysplasias as
      well as in the central cells of grade II and III squamous cell carcinomas (SCCs).
      Overexpression of collagen XVII was found at the invasive front of the tumors.
      Collagen XVII and its cleaved ectodomain were characterized from culture extracts
      and precipitates of oral keratinocytes, tongue carcinoma cells, and tumor tissue
      extract. Malignant cell lines exhibited increased collagen XVII expression in
      immunoblotting analysis. In oral keratinocytes, collagen XVII gene expression was
      significantly induced by PMA but not by the inflammatory cytokines TGF-beta1, TNF
      alpha, EGF, IL-1beta, and IL-6. These results indicate altered expression of
      collagen XVII at different stages of carcinogenesis and suggest a correlation
      between overexpression of collagen XVII and tumor progression. The reduced
      collagen XVII expression at the early step of carcinogenesis may reflect
      disturbed keratinocyte adhesion to the basement membrane.

PMID- 12810843
TI  - An improved chemical fixation method suitable for immunogold localization of
      green fluorescent protein in the Golgi apparatus of tobacco Bright Yellow (BY-2)
      cells.
AB  - In plant systems, the green fluorescent protein (GFP) is increasingly used as a
      marker to study dynamics of the secretory apparatus using fluorescence
      microscopy. The purpose of this study was to immunogold localize the GFP, at the
      electron microscopic level, in a line of tobacco BY-2-cultured cells, expressing
      a GFP-tagged Golgi glycosyltransferase. To this end we have developed a simple,
      one-step chemical fixation method that allow good structural preservation and
      specific labeling with anti-GFP antibodies. Using this method, we have been able
      to show that an N-glycan GFP-tagged xylosyltransferase is specifically associated
      with Golgi stacks of BY-2 transformed cells and is preferentially located in
      medial cisternae. As an alternative to cryofixation methods, such as high
      pressure freezing, which requires specialized and expensive equipment not
      available in most laboratories, this method offers researchers the opportunity to
      investigate GFP-tagged proteins of the endomembrane system in tobacco BY-2 cells.

PMID- 12810844
TI  - Analysis of the mouse CSF-1 gene promoter in a transgenic mouse model.
AB  - CSF-1 stimulates monocyte and osteoclast populations. However, the molecular
      mechanisms involved in regulating CSF-1 gene expression are unclear. To identify
      regulatory regions that control normal CSF-1 gene expression, a -774/+183-bp
      fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo.
      Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA
      compared to ARH-77 B cells that lack CSF-1 gene expression. Transient
      transfection of osteoblasts with promoter deletion constructs showed that the 
      774-bp fragment conferred the highest transcriptional activity and contained
      activator and repressor sequences. To assess the ability of the CSF-1 promoter to
      confer normal tissue expression of CSF-1, transgenic mice containing the 
      774/+183-bp region driving the E. coli beta-galactosidase (lacZ) reporter gene
      were generated. beta-Gal analysis of whole tissue extracts showed transgene
      expression in all tissues tested except liver and kidney. At the cellular level,
      the pattern of beta-gal expression in the spleen, thymus, bone, lung, and testes
      of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non
      transgenic littermates detected by in situ hybridization. This region also
      directed appropriate transgene expression to sites in other tissues known to
      synthesize CSF-1, with the exception of the liver and kidney. These findings
      indicate that the -774-bp fragment contains cis-acting elements sufficient to
      direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be
      useful for studying the transcriptional mechanisms involved in regulating CSF-1
      gene expression in tissues throughout development.

PMID- 12810845
TI  - Spatial distribution analysis of AT- and GC-rich regions in nuclei using
      corrected fluorescence resonance energy transfer.
AB  - We employed microscopic intensity-based fluorescence resonance energy transfer
      (FRET) images with correction by donor and acceptor concentrations to obtain
      unbiased maps of spatial distribution of the AT- and GC-rich DNA regions in
      nuclei. FRET images of 137 bovine aortic endothelial cells stained by the AT
      specific donor Hoechst 33258 and the GC-specific acceptor 7-aminoactinomycin D
      were acquired and corrected for the donor and acceptor concentrations by the
      Gordon's method based on the three fluorescence filter sets. The corrected FRET
      images were quantitatively analyzed by texture analysis to correlate the spatial
      distribution of the AT- and GC-rich DNA regions with different phases of the cell
      cycle. Both visual observation and quantitative texture analysis revealed an
      increased number and size of the low FRET efficiency centers for cells in the
      G(2)/M-phases, compared to the G(1)-phase cells. We have detected cell cycle
      dependent changes of the spatial organization and separation of the AT- and GC
      rich DNA regions. Using the corrected FRET (cFRET) technique, we were able to
      detect early DNA separation stages in late interphase nuclei.

PMID- 12810846
TI  - Fluorogenic substrate [Ala-Pro]2-cresyl violet but not Ala-Pro-rhodamine 110 is
      cleaved specifically by DPPIV activity: a study in living Jurkat cells and
      CD26/DPPIV-transfected Jurkat cells.
AB  - Fluorogenic substrates [Ala-Pro](2)-cresyl violet and Ala-Pro-rhodamine 110 have
      been tested for microscopic detection of protease activity of dipeptidyl
      peptidase IV (DPPIV) in living cells. DPPIV activity is one of the many functions
      of the multifunctional or moonlighting protein CD26/DPPIV. As a model we used
      Jurkat cells, which are T-cells that lack CD26/DPPIV expression, and CD26/DPPIV
      transfected Jurkat cells. Ala-Pro-rhodamine 110 is not fluorescent, but after
      proteolytic cleavage rhodamine 110 fluoresces. [Ala-Pro](2)-cresyl violet is
      fluorescent by itself but proteolytic cleavage into cresyl violet induces a shift
      to longer wavelengths. This phenomenon enables the simultaneous determination of
      local (intracellular) substrate and product concentrations, which is important
      for analysis of kinetics of the cleavage reaction. [Ala-Pro](2)-cresyl violet,
      but not Ala-Pro-rhodamine 110, appeared to be specific for DPPIV. When
      microscopic analysis is performed on living cells during the first minutes of the
      enzyme reaction, DPPIV activity can be precisely localized in cells with the use
      of [Ala-Pro](2)-cresyl violet. Fluorescent product is rapidly internalized into
      submembrane granules in transfected Jurkat cells and is redistributed
      intracellularly via internalization pathways that have been described for
      CD26/DPPIV. We conclude that [Ala-Pro](2)-cresyl violet is a good fluorogenic
      substrate to localize DPPIV activity in living cells when the correct wavelengths
      are used for excitation and emission and images are captured in the early stages
      of the enzyme reaction.

PMID- 12810847
TI  - Expression of Notch1 and Jagged2 in the enteric nervous system.
AB  - The Notch signaling pathway is a vitally important pathway in regulating brain
      development. To explore the involvement of the Notch pathway in neuronal cells of
      adult rat gut, we investigated the expression of Notch1 and Jagged2 by in situ
      hybridization (ISH) and immunohistochemistry (IHC). In the enteric nervous
      system, Notch1 and Jagged2 were expressed in ganglia of the submucosal and
      myenteric plexus. Notch1 was preferentially expressed in cholinergic neurons
      lacking calretinin or nitric oxide synthase (NOS), whereas Jagged2 was present in
      most neuron subtypes. We propose that Notch1 and Jagged2 have a continuing role
      in the maintenance and function of neuronal cells in the adult enteric nervous
      system.

PMID- 12810848
TI  - Localization of thioredoxin-interacting protein (TXNIP) mRNA in epithelium of
      human gastrointestinal tract.
AB  - Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin.
      However, its role in the gastrointestinal (GI) epithelium is as yet unknown.
      Using in situ hybridization, we demonstrated that mRNA of TXNIP was
      differentially expressed in the epithelium of the human GI tract. TXNIP
      transcript was especially prominent in terminal differentiated cells. TXNIP was
      also highly expressed in lymphocytes in the lymphoid follicles. Our results
      suggest a new potential role of TXNIP in the differentiation of epithelial cells
      and in mucosal immunity of the GI tract.

PMID- 12810849
TI  - HOPE fixation of cytospin preparations of human cells for in situ hybridization
      and immunocytochemistry.
AB  - In primary or cultured cells, in situ hybridization (ISH) or immunocytochemistry
      (ICC) is often performed on tissue that has been fixed by paraformaldehyde or
      Carnoy's. Recently we reported an optimized HOPE (HEPES-glutamic acid buffer
      mediated organic solvent protection effect) fixation protocol for ISH targeting
      mRNA in lung tissues. We have now examined whether HOPE fixation could also be
      used on in vitro cultured cells for targeting mRNA by ISH or proteins by ICC on
      cytospin preparations. Using the myeloid stem cell line KG-1a as a model system,
      we showed that HOPE fixation can be applied for ISH and ICC on cultured cells.
      HOPE can be used with cells and tissues and with a broad spectrum of
      immunohistocytochemical and molecular techniques.

PMID- 12810850
TI  - Calmodulin mediates Ca2+-dependent modulation of M-type K+ channels.
AB  - To quantify the modulation of KCNQ2/3 current by [Ca2+]i and to test if
      calmodulin (CaM) mediates this action, simultaneous whole-cell recording and Ca2+
      imaging was performed on CHO cells expressing KCNQ2/3 channels, either alone, or
      together with wild-type (wt) CaM, or dominant-negative (DN) CaM. We varied
      [Ca2+]i from <10 to >400 nM with ionomycin (5 microM) added to either a 2 mM
      Ca2+, or EGTA-buffered Ca2+-free, solution. Coexpression of wt CaM made KCNQ2/3
      currents highly sensitive to [Ca2+]i (IC50 70 +/- 20 nM, max inhibition 73%, n =
      10). However, coexpression of DN CaM rendered KCNQ2/3 currents largely [Ca2+]i
      insensitive (max inhibition 8 +/- 3%, n = 10). In cells without cotransfected
      CaM, the Ca2+ sensitivity was variable but generally weak. [Ca2+]i modulation of
      M current in superior cervical ganglion (SCG) neurons followed the same pattern
      as in CHO cells expressed with KCNQ2/3 and wt CaM, suggesting that endogenous M
      current is also highly sensitive to [Ca2+]i. Coimmunoprecipitations showed
      binding of CaM to KCNQ2-5 that was similar in the presence of 5 mM Ca2+ or 5 mM
      EGTA. Gel-shift analyses suggested Ca2+-dependent CaM binding to an "IQ-like"
      motif present in the carboxy terminus of KCNQ2-5. We tested whether bradykinin
      modulation of M current in SCG neurons uses CaM. Wt or DN CaM was exogenously
      expressed in SCG cells using pseudovirions or the biolistic "gene gun." Using
      both methods, expression of both wt CaM and DN CaM strongly reduced bradykinin
      inhibition of M current, but for all groups muscarinic inhibition was unaffected.
      Cells expressed with wt CaM had strongly reduced tonic current amplitudes as
      well. We observed similar [Ca2+]i rises by bradykinin in all the groups of cells,
      indicating that CaM did not affect Ca2+ release from stores. We conclude that M
      type currents are highly sensitive to [Ca2+]i and that calmodulin acts as their
      Ca2+ sensor.

PMID- 12810851
TI  - The osmoregulatory and the amino acid-regulated responses of system A are
      mediated by different signal transduction pathways.
AB  - The osmotic response of system A for neutral amino acid transport has been
      related to the adaptive response of this transport system to amino acid
      starvation. In a previous study (Ruiz-Montasell, B., M. Gomez-Angelats, F.J.
      Casado, A. Felipe, J.D. McGivan, and M. Pastor-Anglada. 1994. Proc. Natl. Acad.
      Sci. USA. 91:9569-9573), a model was proposed in which both responses were
      mediated by different mechanisms. The recent cloning of several isoforms of
      system A as well as the elucidation of a variety of signal transduction pathways
      involved in stress responses allow to test this model. SAT2 mRNA levels increased
      after amino acid deprivation but not after hyperosmotic shock. Inhibition of p38
      activity or transfection with a dominant negative p38 did not alter the response
      to amino acid starvation but partially blocked the hypertonicity response.
      Inhibition of the ERK pathway resulted in full inhibition of the adaptive
      response of system A and no increase in SAT2 mRNA levels, without modifying the
      response to hyperosmolarity. Similar results were obtained after transfection
      with a dominant negative JNK1. The CDK2 inhibitor peptide-II decreased the
      osmotic response in a dose-dependent manner but did not have any effect on the
      adaptive response of system A. In summary, the previously proposed model of up
      regulation of system A after hypertonic shock or after amino acid starvation by
      separate mechanisms is now confirmed and the two signal transduction pathways
      have been identified. The involvement of a CDK-cyclin complex in the osmotic
      response of system A links the activity of this transporter to the increase in
      cell volume previous to the entry in a new cell division cycle.

PMID- 12810852
TI  - Bimodal action of protons on ATP currents of rat PC12 cells.
AB  - The mode of action of extracellular protons on ATP-gated P2X2 receptors remains
      controversial as either enhancement or depression of ATP-mediated currents has
      been reported. By investigating, at different pH, the electrophysiological effect
      of ATP on P2X2 receptors and complementing it with receptor modelling, the
      present study suggests a unified mechanism for both potentiation and inactivation
      of ATP receptors by protons. Our experiments on patch-clamped PC12 cells showed
      that, on the same cell, mild acidification potentiated currents induced by low
      ATP concentrations (<0.1 mM) and attenuated responses to high ATP concentrations
      (>1 mM) with emergence of current fading and rebound. To clarify the nature of
      the ATP/H+ interaction, we used the Ding and Sachs's "loop" receptor model which
      best describes the behavior of such receptors with two open states linked via one
      inactivated state. No effects by protons could be ascribed to H+-mediated open
      channel block. However, by assuming that protons facilitated binding of ATP to
      resting as well as open receptors, the model could closely replicate H+-induced
      potentiation of currents evoked by low ATP doses plus fading and rebound induced
      by high ATP doses. The latter phenomenon was due to receptor transition to the
      inactive state. The present data suggest that the high concentration of protons
      released with ATP (and catecholamines) from secretory vesicles may allow a dual
      action of H+ on P2X2 receptors. This condition might also occur on P2X2 receptors
      of central neurons exposed to low pH during ischemia.

PMID- 12810853
TI  - Plant culture: thirteen seasonal pieces. July--metamorphosis.

PMID- 12810854
TI  - Differential expression of fatty acid synthase genes, Acl, Fat and Kas, in
      Capsicum fruit.
AB  - The biosynthesis of capsaicinoids in the placenta of chilli fruit is modelled to
      require components of the fatty acid synthase (FAS) complex. Three candidate
      genes for subunits in this complex, Kas, Acl, and Fat, isolated based on
      differential expression, were characterized. Transcription of these three genes
      was placental-specific and RNA abundance was positively correlated with degree of
      pungency. Kas and Acl were mapped to linkage group 1 and Fat to linkage group 6.
      None of the genes is linked to the pungency locus, C, on linkage group 2. KAS
      accumulation was positively correlated with pungency. Western blots of placental
      extracts and histological sections both demonstrated that the accumulation of
      this enzyme was correlated with fruit pungency and KAS was immunolocalized to the
      expected cell layer, the placental epidermis. Enzyme activity of the recombinant
      form of the placental-specific KAS was confirmed using crude cell extracts. These
      FAS components are fruit-specific members of their respective gene families.
      These genes are predicted to be associated with Capsicum fruit traits, for
      example, capsaicinoid biosynthesis or fatty acid biosynthesis necessary for
      placental development.

PMID- 12810855
TI  - Virus-induced silencing of sterol biosynthetic genes: identification of a
      Nicotiana tabacum L. obtusifoliol-14alpha-demethylase (CYP51) by genetic
      manipulation of the sterol biosynthetic pathway in Nicotiana benthamiana L.
AB  - Obtusifoliol-14alpha-demethylase (CYP51) is implicated in plant sterol
      biosynthesis. An Arabidopsis expressed sequence tag encoding a CYP51 was used as
      a probe to isolate Nicotiana tabacum L. cDNAs. Two types of cDNA clones were
      identified. Nt CYP51-1 and Nt CYP51-2 shared 97% identity together and around 75%
      with other plant CYP51s. The function of the encoded enzyme has been demonstrated
      in planta by manipulating the sterol biosynthetic pathway at the gene level. The
      endogenous CYP51 of Nicotiana benthamiana was silenced upon inoculation of the
      plantlets with POTATO VIRUS X::Nt CYP51-1 transcripts. This resulted in the
      accumulation of obtusifoliol, the substrate of CYP51, and other 14alpha-methyl
      sterols, with a concomitant growth reduction phenotype. Virus-induced gene
      silencing was also applied to another steroidogenic enzyme, the Delta7-sterol
      C5(6)-desaturase, and this resulted in the accumulation of Delta7-sterols in
      infected plants instead of the pathway end-products Delta5-sterols.

PMID- 12810856
TI  - Response of purely symbiotic and NO3-fed nodulated plants of Lupinus luteus and
      Vicia atropurpurea to ultraviolet-B radiation.
AB  - The effects of elevated UV-B radiation on growth, symbiotic function and
      concentration of metabolites were assessed in purely symbiotic and NO3-fed
      nodulated plants of Lupinus luteus and Vicia atropurpurea grown outdoors either
      on tables under supplemental UV-B radiation or in chambers covered with different
      types of plexi-glass to attenuate solar ultraviolet radiation. Moderately and
      highly elevated UV-B exposures simulating 15% and 25% ozone depletion as well as
      sub- ambient UV-B did not alter organ growth, plant total dry matter and N
      content per plant in both L. luteus and V. atropurpurea. In contrast, elevated UV
      B increased (P <0.05) flavonoid and anthocyanin concentrations in roots and
      leaves of L. luteus, but not of V. atropurpurea. Feeding nodulated plants of L.
      luteus under elevated UV-B radiation with 2 mM NO3 increased (P <0.05) nodule,
      leaf and total dry matter, and whole plant N content. With V. atropurpurea, NO3
      reduced (P <0.05) nodule activity, root %N and concentrations of flavonoids,
      anthocyanins in roots and leaves and soluble sugars in roots, in contrast to an
      observed increase (P <0.05) in nodule dry matter per plant. Similarly, supplying
      2 mM NO3 to L. luteus plants exposed to sub-ambient UV-B radiation significantly
      reduced individual organ growth, plant total biomass, nodule dry matter, nodule
      %N, and whole plant N content, as well as root concentrations of flavonoids,
      anthocyanins, soluble sugars, and starch of L. luteus, but not V. atropurpurea
      plants. These results show no adverse effect of elevated UV-B radiation on growth
      and symbiotic function of L. luteus and V. atropurpurea plants. However, NO3
      supply promoted growth in L. luteus plants exposed to the highly elevated UV-B
      radiation.

PMID- 12810858
TI  - Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus
      infection and AIDS.
AB  - AIDS, caused by the retroviruses human immunodeficiency virus type 1 and type 2
      (HIV-1 and HIV-2), has reached pandemic proportions. Therefore, it is critical to
      understand how HIV causes AIDS so that appropriate therapies can be formulated.
      Primarily, HIV infects and kills CD4(+) T lymphocytes, which function as
      regulators and amplifiers of the immune response. In the absence of effective
      anti-retroviral therapy, the hallmark decrease in CD4(+) T lymphocytes during
      AIDS results in a weakened immune system, impairing the body's ability to fight
      infections or certain cancers such that death eventually ensues. The major
      mechanism for CD4(+) T cell depletion is programmed cell death (apoptosis), which
      can be induced by HIV through multiple pathways. Death of HIV-infected cells can
      result from the propensity of infected lymphocytes to form short-lived syncytia
      or from an increased susceptibility of the cells to death. However, the apoptotic
      cells appear to be primarily uninfected bystander cells and are eradicated by two
      different mechanisms: either a Fas-mediated mechanism during activation-induced
      cell death (AICD), or as a result of HIV proteins (Tat, gp120, Nef, Vpu) released
      from infected cells stimulating apoptosis in uninfected bystander cells. There is
      also evidence that as AIDS progresses cytokine dysregulation occurs, and the
      overproduction of type-2 cytokines (IL-4, IL-10) increases susceptibility to AICD
      whereas type-1 cytokines (IL-12, IFN-gamma) may be protective. Clearly there are
      multiple causes of CD4(+) T lymphocyte apoptosis in AIDS and therapies that block
      or decrease that death could have significant clinical benefit.

PMID- 12810857
TI  - Differential expression of two type-A response regulators in plants and cell
      cultures of Catharanthus roseus (L.) G. Don.
AB  - Two full-length cDNAs named CrRR2 and CrRR3 have been isolated by PCR from a C.
      roseus cDNA library. The first one encodes a 154 amino acid putative protein with
      a high percentage of identity with the Arabidopsis thaliana response regulators
      ARR16 and ARR17, and is not expressed in C. roseus organs and cell cultures. The
      second one encodes a 188 amino acid ORF sharing the highest homologies with the
      A. thaliana ARR8 and ARR9 response regulators. Its expression is root-specific
      and the transcripts are transiently up-regulated after trans-zeatin treatment in
      C. roseus suspension cells. CrRR3 protein might be involved in the cytokinin
      enhanced alkaloid production in C. roseus cell cultures.

PMID- 12810859
TI  - Construction and in vivo infection of a new simian/human immunodeficiency virus
      chimera containing the reverse transcriptase gene and the 3' half of the genomic
      region of human immunodeficiency virus type 1.
AB  - A new simian/human immunodeficiency virus (SHIV) chimera with the reverse
      transcriptase (RT)-encoding region of pol, in addition to the 3' region encoding
      vpr, vpu, tat, rev, env and nef of HIV-1, on an SIV(mac) (SIV from a macaque
      monkey) background was constructed. This new SHIV chimera, named SHIVrt/3rn,
      could replicate in monkey peripheral blood mononuclear cells (PBMCs) as well as
      in the human and monkey CD4(+) T-cell lines M8166 and HSC-F. Since SHIVrt/3rn
      contains the RT gene of HIV-1, replication of the virus in M8166 cells was
      inhibited by an HIV-1-specific non-nucleoside RT inhibitor, MKC-442, with a
      sensitivity similar to that of HIV-1. To investigate the replication competence
      of SHIVrt/3rn in vivo, two rhesus monkeys were inoculated intravenously with the
      virus. At 2 to 4 weeks post-inoculation (p.i.), plasma viral RNA loads of both
      monkeys showed a peak value of more than 10(4) copies ml(-1). Infectious virus
      was isolated from the PBMCs of one monkey at 2 and 3 weeks p.i. and from the
      other at 4 weeks p.i. Moreover, proviral DNA was detected constantly throughout
      the observation period, starting from 3 weeks p.i. An antibody response, detected
      first at 3 weeks p.i., was maintained at high titres. These results indicate that
      SHIVrt/3rn can infect and replicate in vivo. SHIVrt/3rn, having part of HIV-1 pol
      in addition to the 3' part of the HIV-1 genome is genetically more close to HIV-1
      than any of the other monkey-infecting SHIVs reported previously.

PMID- 12810860
TI  - Infection of macaques with simian immunodeficiency virus induces a species
      specific antibody response to major histocompatibility complex class I and class
      II molecules.
AB  - Envelopes of retroviruses, including human immunodeficiency virus and simian
      immunodeficiency virus (SIV), contain host cell proteins that potentially
      represent novel targets for vaccine development. We show here that sera from
      rhesus macaques recognized simian major histocompatibility complex (MHC)
      molecules in response to infection with SIV. Antibodies from these animals did
      not cross-react with human MHC antigens on mitogen-activated peripheral blood
      mononuclear cells. The development of antibodies to MHC class I alpha-chain did
      not correlate with anti-SIV envelope antibody responses, suggesting that these
      antibodies did not arise through molecular mimicry. In contrast to the species
      specific response in infected animals, sera from animals vaccinated with
      inactivated human cell-grown SIV reacted to both human and rhesus MHC class I and
      class II molecules.

PMID- 12810861
TI  - Gene expression analysis of murine cells producing amphotropic mouse leukaemia
      virus at a cultivation temperature of 32 and 37 degrees C.
AB  - Cultivation of retrovirus packaging cells at 32 degrees C represents a common
      procedure to achieve high titres in mouse retrovirus production. Gene expression
      profiling of mouse NIH 3T3 cells producing amphotropic mouse leukaemia virus
      4070A revealed that 10 % of the 1176 cellular genes investigated were regulated
      by temperature shift (37/32 degrees C), while 5 % were affected by retrovirus
      infection. Strikingly, retrovirus production at 32 degrees C activated the
      cholesterol biosynthesis/transport pathway and caused an increase in plasma
      membrane cholesterol levels. Furthermore, these conditions resulted in
      transcriptional activation of smoothened (smo), patched (ptc) and gli-1; Smo, Ptc
      and Gli-1, as well as cholesterol, are components of the Sonic hedgehog (Shh)
      signalling pathway, which directs pattern formation, diversification and
      tumourigenesis in mammalian cells. These findings suggest a link between
      cultivation at 32 degrees C, production of MLV-A and the Shh signalling pathway.

PMID- 12810862
TI  - Requirement for cyclophilin A for the replication of vesicular stomatitis virus
      New Jersey serotype.
AB  - Several host proteins have been shown to play key roles in the life-cycle of
      vesicular stomatitis virus (VSV). We have identified an additional host protein,
      cyclophilin A (CypA), a chaperone protein possessing peptidyl cis-trans prolyl
      isomerase activity, as one of the cellular factors required for VSV replication.
      Inhibition of the enzymatic activity of cellular CypA by cyclosporin A (CsA) or
      SDZ-211-811 resulted in a drastic inhibition of gene expression by VSV New Jersey
      (VSV-NJ) serotype, while these drugs had a significantly reduced effect on the
      genome expression of VSV Indiana (VSV-IND) serotype. Overexpression of a
      catalytically inactive mutant of CypA resulted in the reduction of VSV-NJ
      replication, suggesting a requirement for functional CypA for VSV-NJ infection.
      It was also shown that CypA interacted with the nucleocapsid (N) protein of VSV
      NJ and VSV-IND in infected cells and was incorporated into the released virions
      of both serotypes. VSV-NJ utilized CypA for post-entry intracellular primary
      transcription, since inhibition of CypA with CsA reduced primary transcription of
      VSV-NJ by 85-90 %, whereas reduction for VSV-IND was only 10 %. Thus, it seems
      that cellular CypA binds to the N protein of both serotypes of VSV. However, it
      performs an obligatory function on the N protein activity of VSV-NJ, while its
      requirement is significantly less critical for VSV-IND N protein function. The
      different requirements for CypA by two serologically different viruses belonging
      to the same family has highlighted the utilization of specific host factors
      during their evolutionary lineages.

PMID- 12810863
TI  - Antibody-mediated growth of infectious salmon anaemia virus in macrophage-like
      fish cell lines.
AB  - Infectious salmon anaemia virus (ISAV), a pathogen in marine aquaculture, belongs
      to the genus Isavirus, family Orthomyxoviridae. There is limited information on
      how ISAV interacts with host defences. To study ISAV-antibody interactions, virus
      neutralization (VN) assays were performed in the cell lines CHSE-214, SHK-1 and
      TO using three strains of ISAV and rabbit or fish anti-ISAV sera. Homologous VN
      titres of >1 : 1280 in CHSE-214 cells corresponded to titres of only 1 : 80 in
      the macrophage-like fish cell lines SHK-1 and TO, despite using 1000 and 2000
      times less virus, respectively. However, rabbit antiserum to infectious
      pancreatic necrosis virus (IPNV) had a VN titre of 1 : 10,260 against IPNV in
      both CHSE-214 and TO cells. Poor ISAV neutralization in TO cells was attributed
      to Fc receptors mediating virus infectivity, because (1) neutralization by rabbit
      antiserum to ISAV was increased 48-fold in the presence of staphylococcal Protein
      A and (2) when using FITC-labelled virus and spectrofluorometry, a significant
      increase (P=0.018) in the intensity of fluorescence of intracellular virus was
      observed in assays of virus-antiserum mixtures in the absence of Protein A as
      compared to those in the presence of Protein A. Neutralization of ISAV with fish
      antisera was observed only in CHSE-214 cells, as Protein A could not restore
      neutralization in TO cells. These findings demonstrate for the first time
      antibody-mediated infection of macrophage-like fish cell lines by a fish virus,
      ISAV, and, as ISAV in Atlantic salmon targets leukocytic and endothelial cells,
      this may have implications for ISA pathogenesis and vaccination.

PMID- 12810864
TI  - The membrane proteins of flaviviruses form ion-permeable pores in the target
      membrane after fusion: identification of the pores and analysis of their possible
      role in virus infection.
AB  - Recently, we presented evidence that the E1 fusion protein of the alphavirus
      Semliki Forest virus forms ion-permeable pores in the target membrane after
      fusion. We proposed that the homologous fusion proteins of flaviviruses and
      hepatitis C virus form similar pores. To test this hypothesis for the E fusion
      protein of flaviviruses, the release of [(3)H]choline from liposomes by the
      flavivirus West Nile (WN) virus was determined. [(3)H]Choline was released at
      mildly acid pH. The pH threshold depended on the lipid composition. Release from
      certain liposomes was activated even at neutral pH. To identify the generation of
      individual pores, single cells were investigated with the patch-clamp technique.
      The formation of individual pores during low pH-induced WN virus entry at the
      plasma membrane occurred within seconds. These experiments were performed in
      parallel with Semliki Forest virus. The results indicated that, similar to
      alphavirus infection, infection with flaviviruses via endosomes leads to the
      formation of ion-permeable pores in the endosome after fusion, which allows the
      flow of protons from the endosome into the cytoplasm during virus entry. However,
      in vitro translation experiments of viral cores showed that, in contrast to
      alphaviruses, which probably need this proton flow for core disassembly, the
      genome RNA of WN virus present in the viral core is directly accessible for
      translation. For entry of flaviviruses, therefore, a second pathway for
      productive infection may exist, in which fusion of the viral membrane is
      activated at neutral pH by contact with a plasma membrane of appropriate lipid
      composition.

PMID- 12810865
TI  - Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in
      mice.
AB  - Enhancement of flavivirus infection in vitro in the presence of subneutralizing
      concentrations of homologous or heterologous antiserum has been well described.
      However, the importance of this phenomenon in the enhancement of flavivirus
      infection in vivo has not been established. In order to study antibody-mediated
      enhancement of flavivirus infection in vivo, we investigated the effect of
      passive immunization of mice with Japanese encephalitis virus (JE) antiserum on
      the outcome of infection with Murray Valley encephalitis virus (MVE). We show
      that prior treatment of mice with subneutralizing concentrations of heterologous
      JE antiserum resulted in an increase in viraemia titres and in mortality
      following challenge with wild-type MVE. Our findings support the hypothesis that
      subneutralizing concentrations of antibody may enhance flavivirus infection and
      virulence in vivo. These findings are of potential importance for the design of
      JE vaccination programs in geographic areas in which MVE co-circulates. Should
      subneutralizing concentrations of antibody remain in the population following JE
      vaccination, it is possible that enhanced disease may be observed during MVE
      epidemics.

PMID- 12810866
TI  - Common host genes are activated in mouse brain by Japanese encephalitis and
      rabies viruses.
AB  - This study identified nine genes whose expression is upregulated in the central
      nervous system (CNS) of mice during Japanese encephalitis virus (JEV) infection.
      These include: cathepsin S, oligoadenylate synthetase (OAS), GARG49/IRG2,
      lymphocyte antigen-6A (Ly-6A), macrophage activation gene-2 (Mpa2), early growth
      response gene1 (Egr1), pyrimidine 5'-nucleotidase (P5N), apolipoprotein D (ApoD)
      and STAT1. Activation of all nine genes during JEV infection was confirmed by
      Northern blot analysis. JEV replication was inhibited in the majority of mice
      immunized with Biken JEV vaccine, and these mice also exhibited reduced
      expression of JEV-inducible CNS genes. Thus, there is a good correlation between
      virus load and upregulation of host CNS genes. It was also demonstrated that all
      the CNS genes activated by JEV are also upregulated during rabies virus
      infection. In addition, GARG49, STAT1, cathepsin S and ApoD are known to be
      upregulated in the CNS by Sindbis virus, an alphavirus, and this supports the
      proposal that common host cell pathways are activated in the CNS by different
      neurotropic viruses.

PMID- 12810867
TI  - Interference in Japanese encephalitis virus infection of Vero cells by a cationic
      amphiphilic drug, chlorpromazine.
AB  - Entry of Japanese encephalitis virus (JEV) into cells was analysed by using the
      vertebrate cell line Vero. Vero cells were treated with chlorpromazine, nystatin
      or cytochalasin D, which inhibit clathrin- and caveola-dependent endocytosis, and
      macropinocytosis of the cells, respectively. Productive JEV infection was
      inhibited by pretreatment with chlorpromazine; the number of JEV antigen-positive
      cells was less than one-fifth of that in untreated cultures, but was not
      significantly decreased by pretreatment with nystatin or cytochalasin. Viral
      antigens were detected in the membrane fractions, but not in the endosome
      fractions from chlorpromazine-treated JEV-inoculated cells. When the cells were
      treated with chlorpromazine, clathrin heavy chain antigen and JEV antigen were
      not detected in cytoplasm by indirect immunofluorescence staining. These results
      indicate that JEV is taken up by cells through the clathrin-dependent endocytic
      pathway, and this process leads to infection.

PMID- 12810868
TI  - Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses.
AB  - This paper investigates the role of CTL and antibody responses in hepatitis C
      virus (HCV) dynamics and pathology. Mathematical models suggest that a strong CTL
      response is required for resolution of HCV infection and that a weak CTL response
      can result in persistent infection. According to the model, establishment of
      persistent infection is accompanied mainly by an ongoing antibody response, while
      CTLs are not maintained at high levels. In the model, this outcome correlates
      with absence of pathology. Persistent infection in the face of an ongoing
      antibody response can result in evolution of antigenic escape. According to the
      model, evolution towards escape from antibodies can shift the balance of immune
      responses so that the weak CTL levels become increasingly more dominant relative
      to antibodies. This shift results in onset of liver pathology as the virus
      evolves towards increased levels of antigenic escape. Therefore, the relative
      balance of the immune response can be a decisive factor that determines whether
      patients are asymptomatic or whether pathology is observed. Virus evolution can
      shift this balance towards pathology over time. Theoretical results are discussed
      in the context of published data.

PMID- 12810869
TI  - Characterization of the expression of the hepatitis C virus F protein.
AB  - Hepatitis C virus (HCV) is an important human pathogen that affects 170 million
      people worldwide. The HCV genome is approximately 9.6 kb in length and encodes a
      polyprotein that is proteolytically cleaved to generate at least 10 mature viral
      protein products. Recently, a new protein, named F, has been described to be
      expressed through a ribosomal frameshift within the capsid-encoding sequence, a
      mechanism unique among members of the family Flavidiridae: Here, expression of
      the F protein was investigated in an in vitro transcription/translation assay.
      Its expression in mammalian cells was confirmed using specific recombinant
      vaccinia viruses; under these conditions, protein expression is dependent on the
      HCV IRES. The F protein was tagged with firefly luciferase or the Myc epitope to
      facilitate its identification. Ribosomal frameshifting was dependent on the
      presence of mutations in the capsid-encoding sequence. No frameshifting was
      detected in the absence of any mutation. Furthermore, analysis of the F protein
      in time-course experiments revealed that the protein is very unstable and that
      its production can be stabilized by the proteasome inhibitor MG132. Finally,
      indirect immunofluorescence studies have localized the F protein in the
      cytoplasm, with notable perinuclear detection.

PMID- 12810870
TI  - Analysis of hepatitis C virus/classical swine fever virus chimeric 5'NTRs:
      sequences within the hepatitis C virus IRES are required for viral RNA
      replication.
AB  - Hepatitis C virus (HCV) is classified in the genus Hepacivirus of the family
      Flaviviridae, whose members have a single-stranded RNA genome of positive
      polarity, which encodes a single polyprotein. Within this family, HCV is closely
      related to viruses of the genus Pestivirus, which includes classical swine fever
      virus (CSFV). Translation of the hepaci- and pestiviral polyprotein is initiated
      by internal entry of ribosomes, promoted by the 5'NTR. The secondary and tertiary
      RNA structures of the HCV and pestivirus 5'NTRs are well conserved, despite the
      fact that their sequences differ significantly from one another. By analogy with
      other positive-stranded RNA viruses, the 5'NTR of HCV is likely to contain cis
      acting determinants for replication as well as the determinants for translation.
      Studies on both signals could be complicated, as these signals might overlap. In
      this study, this problem was addressed by constructing chimeric HCV/CSFV 5'NTRs.
      A two-step analysis of these 5'NTRs was performed: (a) in a translation assay,
      which provided the possibility to study translation independently of the possible
      effects on replication; and (b) in a replication assay, in which were studied
      only the chimeric 5'NTRs for which IRES-dependent translation was demonstrated.
      An overlap was observed between HCV RNA elements involved in these processes.
      Exchange of domain II had a minor effect on the translation efficiency of the
      chimeric 5'NTRs, while replication of subgenomic replicons with these chimeric
      5'NTRs was abolished. Exchange of domain III subdomains severely decreased
      translation activity, while replication was maintained.

PMID- 12810871
TI  - Differential effects of bovine viral diarrhoea virus on monocytes and dendritic
      cells.
AB  - Various pathogens have been shown to infect antigen-presenting cells and affect
      their capacity to interact with and stimulate T-cell responses. We have used an
      antigenically identical pair of non-cytopathic (ncp) and cytopathic (cp) bovine
      viral diarrhoea virus (BVDV) isolates to determine how the two biotypes affect
      monocyte and dendritic cell (DC) function. We have shown that monocytes and DCs
      are both susceptible to infection with ncp BVDV and cp BVDV in vitro. In
      addition, monocytes infected with ncp BVDV were compromised in their ability to
      stimulate allogeneic and memory CD4(+) T cell responses, but DCs were not
      affected. This was not due to down-regulation of a number of recognized co
      stimulatory molecules including CD80, CD86 and CD40. Striking differences in the
      response of the two cell types to infection with cytopathic virus were seen.
      Dendritic cells were not susceptible to the cytopathic effect caused by cp BVDV,
      whereas monocytes were killed. Analysis of interferon (IFN)-alpha/beta production
      showed similar levels in monocytes and DCs exposed to cp BVDV, but none was
      detected in cells exposed to ncp BVDV. We conclude that the prevention of cell
      death in DCs is not associated with enhanced production of IFN-alpha/beta, as
      proposed for influenza virus, but is by a distinct mechanism.

PMID- 12810872
TI  - Characterization of formaldehyde-inactivated poliovirus preparations made from
      live-attenuated strains.
AB  - Formaldehyde-inactivated virus samples from type 1 poliovirus live-attenuated
      strains were prepared in the laboratory. The effect of treatment with
      formaldehyde on virus infectivity and immunogenicity in mice was investigated and
      the results compared with those from Mahoney wild-type poliovirus strain, the
      common type 1 component in commercial inactivated polio vaccines (IPV).
      Differences in the potency and specificity between these experimental vaccines
      were identified in both normal mice and transgenic mice expressing the human
      poliovirus receptor. The possible advantages/disadvantages of using live
      attenuated strains for IPV production are discussed in the context of the global
      polio eradication initiative. A novel transgenic mouse model to study in vivo the
      immune protection induced by IPV preparations is described.

PMID- 12810873
TI  - Flock house virus replicates and expresses green fluorescent protein in
      mosquitoes.
AB  - Flock house virus (FHV) is a non-enveloped, positive-sense RNA virus of insect
      origin that belongs to the family Nodaviridae. FHV has been shown to overcome the
      kingdom barrier and to replicate in plants, insects, yeast and mammalian cells.
      Although of insect origin, FHV has not previously been shown to replicate in
      mosquitoes. We have tested FHV replication in vitro in C6/36 cells (derived from
      neonatal Aedes albopictus) and in vivo in four different genera of mosquitoes,
      Aedes, Culex, Anopheles and Armigeres. FHV replicated to high titres in C6/36
      cells that had been subcloned to support maximum growth of FHV. When adult
      mosquitoes were orally fed or injected with the virus, FHV antigen was detected
      in various tissues and infectious virus was recovered. Vectors developed from an
      infectious cDNA clone of a defective-interfering RNA, derived from FHV genomic
      RNA2, expressed green fluorescent protein in Drosophila cells and adult
      mosquitoes. This demonstrates the potential of FHV-based vectors for expression
      of foreign genes in mosquitoes and possibly other insects.

PMID- 12810874
TI  - The cypovirus Diadromus pulchellus RV-2 is sporadically associated with the
      endoparasitoid wasp D. pulchellus and modulates the defence mechanisms of pupae
      of the parasitized leek-moth, Acrolepiopsis assectella.
AB  - Diadromus pulchellus is a solitary endoparasitoid wasp that parasitizes the pupae
      of the leek-moth, Acrolepiosis assectella (Lepidoptera). Hitherto, every
      individual D. pulchellus from France that has been investigated was infected by
      an orthoreovirus, DpRV-1, and an ascovirus, DpAV-4. Recently, a new strain of D.
      pulchellus, established from a French field population, was found to be able to
      develop on leek-moth pupae, but lacked both DpRV-1 and DpAV-4. However, all these
      wasps were infected with a new cypovirus, DpRV-2. This cypovirus is transmitted
      to the A. assectella pupae at each wasp oviposition and is replicated mainly in
      the gut cells of the parasitized pupae. DpRV-2, like the ascovirus DpAV-4, is
      able to inhibit the defence reaction of A. assectella pupae and so contributes to
      the parasitic success of D. pulchellus wasps.

PMID- 12810875
TI  - Early interactions of marine birnavirus infection in several fish cell lines.
AB  - Marine birnavirus (MABV), a member of the genus Aquabirnavirus, family
      Birnaviridae, is an unenveloped icosahedral virus with two genomes of double
      stranded RNA. The mechanisms of MABV adsorption and penetration are still
      undetermined. This work examined MABV infection in susceptible and resistant fish
      cell lines. MABV adsorbed not only onto the cell surfaces of susceptible (CHSE
      214 and RSBK-2) cells but also onto resistant (FHM and EPC) cells. Furthermore,
      the virus entered the cytoplasm through the endocytotic pathway in CHSE-214, RSBK
      2 and FHM cells but did not penetrate EPC cells. Thus, restriction of the MABV
      replication cycle is different between resistant FHM and EPC cells. The virus was
      found to bind to an around 250 kDa protein on CHSE-214, RSBK-2, FHM and EPC
      cells. Thus, this 250 kDa protein may be a major MABV receptor that exists in the
      plasma membranes of all four cell lines examined. This result suggests further
      that another receptor for virus penetration may exist in CHSE-214, RSBK-2 and FHM
      cells but not in EPC cells.

PMID- 12810876
TI  - Functional dissection of the baculovirus late expression factor-8 gene: sequence
      requirements for late gene promoter activation.
AB  - The late expression factor-8 gene (lef-8) of Autographa californica M
      nucleopolyhedrovirus encodes the largest subunit of the virally encoded DNA
      directed RNA polymerase specific for the transcription of late and very late
      viral genes. The sequence of lef-8 predicts a C-terminal motif of 13 amino acids
      that is conserved in other polymerases. Detailed mutagenesis throughout lef-8 was
      performed, including this C-terminal motif, to define sequences required for late
      promoter activation. It was found that the conserved C-terminal motif was
      critical for late gene expression. In addition, regions throughout the entire lef
      8-encoding sequence were important for optimal function, suggesting complex
      protein-protein and protein-DNA interrelationships in the late gene-specific
      viral transcriptosome.

PMID- 12810877
TI  - Comparative analysis of the genomes of Rachiplusia ou and Autographa californica
      multiple nucleopolyhedroviruses.
AB  - The Rachiplusia ou multiple nucleopolyhedrovirus (RoMNPV) is a variant of
      Autographa californica MNPV (AcMNPV) but is significantly more virulent against
      several major agricultural pests. The genome sequence of the R1 strain of RoMNPV
      was determined and compared to that of AcMNPV strain C6. The RoMNPV genome is
      approximately 131.5 kbp with a G+C content of 39.1 %. The homologous repeat
      regions (hrs) described for AcMNPV-C6 are present in RoMNPV-R1 but the hrs of
      RoMNPV have fewer palindromic repeats. The RoMNPV-R1 nucleotide sequence is
      almost completely collinear with the sequence of AcMNPV-C6 and contains
      homologues of 150 of the 155 ORFs described for AcMNPV-C6. Deletions, insertions
      and substitutions have resulted in the loss of homologues for AcMNPV ORFs ac2
      (bro), ac3 (ctl), ac97, ac121 and ac140 from the RoMNPV genome. The average amino
      acid sequence identity between RoMNPV and AcMNPV ORFs is 96.1 % and there are
      differences in promoter motif composition for 23 of these ORFs. Maximum
      likelihood analysis of selection pressures on AcMNPV and RoMNPV ORFs indicate
      that ORFs ro18/ac20-ac21 (arif-1) and ro135/ac143 (odv-e18) have undergone
      positive selection.

PMID- 12810878
TI  - Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against
      hepatitis B virus and herpes simplex virus.
AB  - It is known that some viruses are able to induce vigorous immune reactions. This
      study shows that inactivated parapoxvirus ovis (Orf virus), strain D1701 (PPVO),
      induces an autoregulatory cytokine response that involves the upregulation of IL
      12, IL-18, IFN-gamma and other T helper 1-type cytokines and their subsequent
      downregulation, which is accompanied by induction of IL-4. An increase in IL-10
      expression was also found in the livers of PPVO-treated mice. PPVO protects mice
      from lethal herpes simplex virus type 1 infection and guinea pigs from recurrent
      genital herpes disease. With dosages as low as 500 000 virus particles, PPVO is
      more potent than the current standard 3TC therapy in hepatitis B virus transgenic
      mice. No signs of inflammation or any other side effects were observed. PPVO
      induces IL-12, TNF-alpha and, together with a suboptimal concentration of
      Concanavalin A, IFN-gamma in human peripheral blood leukocytes as well. The
      principle of an autoregulatory cytokine induction by an inactivated virus might
      have advantages over existing immune therapies and it is concluded that
      inactivated PPVO should be investigated further for its potential use in
      antiviral therapy.

PMID- 12810879
TI  - Neutralizing antibody to gB2 human cytomegalovirus does not prevent reactivation
      in patients with human immunodeficiency virus infection.
AB  - The incidence of human cytomegalovirus (CMV) genotype gB2 (UL55) is high in
      patients with human immunodeficiency virus (HIV) infection in the San Francisco
      Bay area of California. Virus neutralizing antibody (NAb) to human CMV strain
      Ad169, a gB2 laboratory strain, was measured prospectively in HIV-infected
      patients, with CD4 T-lymphocyte counts <200, who were at risk for CMV-associated
      disease. Patients were grouped according to CMV DNA copy number, as quantified by
      PCR, and presence or absence of CMV-induced retinitis. Mean NAb titres were
      similar in all patient groups and unrelated to either virus load or outcome of
      CMV infection. Both gB2 and mixtures of gB2 with other gB genotypes were
      represented in isolates from blood and/or urine, even in the presence of high
      titres of antibody to the gB2 genotype challenge virus.

PMID- 12810880
TI  - Differential effects of glycoprotein B epitope-specific antibodies on human
      cytomegalovirus-induced cell-cell fusion.
AB  - Attachment of, and cell-cell fusion induced by, human cytomegalovirus were
      studied in the presence of neutralizing monospecific antibodies against antigenic
      domains 1 (AD-1) or 2 (AD-2) of glycoprotein B (gB, gpUL55). Efficient inhibition
      of the virion-mediated fusion event was consistently observed for the human AD-2
      specific antibody as determined by a reporter gene activation assay based on
      permissive astrocytoma cells. In contrast, antibodies directed against the major
      neutralizing gB epitope AD-1 reduced fusion only by 20-60 %. Virus attachment via
      heparan sulfate was unaffected by the antibodies under the conditions used. Virus
      receptor binding as examined by heparin treatment of adsorbed virus was
      significantly reduced only if the virus had been coated with the AD-2-specific
      antibody. Neutralization of virus infectivity by the AD-2-specific antibody thus
      seems most likely to result from interference with a receptor-binding event
      during initial virus-host cell interaction.

PMID- 12810881
TI  - No role for Epstein-Barr virus in Dutch hepatocellular carcinoma: a study at the
      DNA, RNA and protein levels.
AB  - Epstein-Barr virus (EBV) has been suggested to play a role in hepatocellular
      carcinoma (HCC). However, reports on detailed EBV transcript analyses in HCCs are
      limited. It was shown recently that expression of the transforming BARF1 (BamHI A
      rightward open reading frame 1) gene of EBV is restricted to latently EBV
      infected epithelial malignancies, i.e. nasopharyngeal carcinoma and gastric
      carcinoma. The aim of this study was to test the presence of EBV in Dutch HCCs. A
      semiquantitative DNA PCR-enzyme immunoassay (PCR-EIA) for the BamHI W fragment of
      EBV was used to assess the presence of EBV in frozen and paraffin-embedded
      tissues of 16 HCCs. In addition, several RNA detection techniques, i.e. nucleic
      acid sequence-based amplification (NASBA), RT-PCR, RNA in situ hybridization
      (RISH) and immunohistochemistry (IHC), were applied. Five of 16 HCCs and two of
      four hepatitis C virus hepatitis samples were weakly positive for EBV DNA by PCR
      EIA. Using sensitive RNA transcription techniques, no transcripts were found for
      BARF1, EBNA-1 and BARTs (BamHI A rightward transcripts) in any of the liver
      tissues tested. In addition, RISH for EBER1/2 and BARTs and IHC for EBNA-1, LMP-1
      and ZEBRA, performed on the paraffin-embedded tissue of the PCR-EIA-positive
      cases and on adjacent non-neoplastic liver tissues, were negative. The absence of
      epithelial-specific BARF1 transcripts and other EBV transcripts and proteins in
      the EBV DNA PCR-positive cases argues strongly against a role for EBV in HCC.

PMID- 12810882
TI  - Localization of the Epstein-Barr virus protein LMP 1 to exosomes.
AB  - The Epstein-Barr virus latent membrane protein (LMP 1) functions as a
      constitutively active signalling molecule and associates in lipid rafts clustered
      with other signalling molecules. Using immunofluorescent confocal microscopy, LMP
      1 was shown to have an heterogeneous distribution among individual cells which
      was not related to the cell cycle stage. LMP 1 was shown to localize to
      intracellular compartments in cells other than the plasma membrane. Co-labelling
      of cells with both an LMP 1 antibody and an antibody to the Golgi protein GS15
      revealed that the intracellular LMP 1 partly co-localized with the Golgi
      apparatus. Further confirmation of intracellular LMP 1 localization was obtained
      by immunoelectron microscopy with rabbit polyclonal LMP 1 antibodies and
      cryosectioning. As well as being present in intracellular foci, LMP 1 co
      localized in part with MHC-II and was present on exosomes derived from a
      lymphoblastoid cell line. Preparations of LMP 1 containing exosomes were shown to
      inhibit the proliferation of peripheral blood mononuclear cells, suggesting that
      LMP 1 could be involved in immune regulation. This may be of particular relevance
      in EBV-associated tumours such as nasopharyngeal carcinoma and Hodgkin's disease,
      as LMP 1-containing exosomes may be taken up by infiltrating T-lymphocytes, where
      LMP 1 could exert an anti-proliferative effect, allowing the tumour cells to
      evade the immune system.

PMID- 12810883
TI  - Prevalence and type spectrum of human papillomaviruses in healthy skin samples
      collected in three continents.
AB  - In order to investigate whether previous findings of ubiquitous skin
      papillomavirus infection in Caucasians apply to populations from other parts of
      the world, skin swab samples from Bangladesh, Japan, Ethiopia and Zambia were
      analysed in parallel with Swedish samples. The prevalence of HPV DNA in the
      material from Bangladesh was 68 %, Japan 54 %, Ethiopia 52 %, Zambia 42 % and
      Sweden 70 %. A great multiplicity of genotypes was demonstrated by the finding of
      88 HPV types or putative types in 142 HPV DNA-positive samples in total. Double
      or multiple genotypes were frequently found in the same sample. The most
      prevalent HPV type was HPV-5, with an overall prevalence of 6.5 %. This was also
      the only type that was found in samples from all of the countries in the study.
      The results presented show that commensal skin HPV infections have a worldwide
      distribution with a very broad spectrum of genotypes.

PMID- 12810884
TI  - A role of the TATA box and the general co-activator hTAF(II)130/135 in promoter
      specific trans-activation by simian virus 40 small t antigen.
AB  - The small t antigen (st-ag) of simian virus 40 can exert pleiotropic effects on
      biological processes such as DNA replication, cell cycle progression and gene
      expression. One possible mode of achieving these effects is through stimulation
      of NFkappaB-responsive genes encoding growth factors, cytokines, transcription
      factors and cell cycle regulatory proteins. Indeed, a previous study has shown
      that st-ag enhanced NFkappaB-mediated transcription. This study demonstrates that
      promoters possessing a consensus TATA box (i.e. TATAAAAG) in the context of
      either NFkappaB- or Sp1-binding sites are trans-activated by st-ag.
      Overexpressing the general transcription factor hTAF(II)130/135, but not
      hTAF(II)28 or hTAF(II)80, stimulated the activity of promoters in a consensus
      TATA box-dependent mode. Converting the consensus TATA motif into a non-consensus
      TATA box strongly impaired activation by st-ag and hTAF(II)130/135. Conversely,
      mutating a non-consensus TATA motif into the consensus TATA box rendered the
      mutated promoter inducible by st-ag and hTAF(II)130/135. Mutation of the TATA box
      had no effect on TNFalpha- or RelA/p65-mediated induction of NFkappaB-responsive
      promoters, indicating a specific st-ag effect on hTAF(II)130/135. St-ag
      stimulated the intrinsic transcriptional activity of hTAF(II)130/135.
      Substitutions in the conserved HPDKGG motif in the N-terminal region or a
      mutation that impaired the interaction with protein phosphatase 2A abrogated the
      ability of st-ag to activate hTAF(II)130/135-mediated transcription. These
      results indicate that trans-activation of promoters by st-ag may depend on a
      consensus TATA motif and suggest that such promoters recruit the general
      transcription factor hTAF(II)130/135.

PMID- 12810885
TI  - Simian virus 40 VP1 capsid protein forms polymorphic assemblies in vitro.
AB  - The simian virus 40 (SV40) capsid is composed of 72 pentamers of VP1, the major
      protein of SV40. These pentamers are arranged in a T=7d icosahedral surface
      lattice, which is maintained by three types of appropriately arranged, non
      equivalent interactions between the pentamers. However, it remains unclear how
      these interactions are achieved. In this study, the in vitro assembly of
      recombinant VP1 was analysed. Electron microscopy observations revealed that
      these recombinant VP1 proteins assembled into structurally polymorphic particles
      depending on environmental conditions. VP1 pentamers assembled efficiently into
      virus-like particles (VLPs) when high concentrations of ammonium sulfate were
      present. However, in the presence of 1 M NaCl and 2 mM CaCl(2) at neutral pH, VP1
      pentamers formed not only VLPs but also produced tiny T=1 icosahedral particles
      and tubular structures. The exclusion of CaCl(2) resulted in the exclusive
      formation of tiny particles. In contrast, in the presence of 150 mM NaCl at pH 5,
      the VP1 pentamers produced only extraordinarily long tubular structures. VP1 is
      thus quite unique in that it can assemble into such diverse structures. These
      observations provide clues that will help elucidate the mechanisms underlying
      SV40 capsid formation.

PMID- 12810886
TI  - Antisense RNAs transcribed from the upstream region of the precore/core promoter
      of hepatitis B virus.
AB  - The bidirectional activity of the precore/core promoter of hepatitis B virus
      (HBV) has been demonstrated in cultured cell lines. However, HBV antisense
      transcripts (asRNAs) have not been demonstrated in vivo. In the present study
      using liver tissue from patients with chronic hepatitis, an anchored 5'RACE
      mapping the 5' ends at position 1680/1681, 1655 or 1609/1602 was carried out. In
      limited cases, RLM-3'RACE detected asRNAs to terminate at four or five
      consecutive dT residues in the 0.7 kb downstream region. PCR of oligo(dT)-primed
      cDNA did not amplify a typical polyadenylated asRNA. RT-PCR using various primers
      did not detect any spliced forms. Competitive RT-PCR estimated the copy numbers
      of the asRNAs to be 0.05-0.4 % of total sense RNAs. All sequenced asRNAs had ORF6
      but, in one patient, the asRNA initiating at position 1680/1681 had additional
      initiation and termination codons in front of ORF6. Therefore, asRNAs are
      transcribed by RNA polymerase III at a low level, encompass a dispensable ORF6
      gene and might be retained in the nucleus. The endogenous asRNAs complementary to
      the common ends of all sense RNAs suggest antisense-mediated self-regulation of
      hepadnavirus.

PMID- 12810887
TI  - Hepatitis B virus: predominance of genotype D in primitive tribes of the Andaman
      and Nicobar islands, India (1989-1999).
AB  - To understand the possible origin of hepatitis B virus (HBV), three of the four
      hyperendemic, primitive accessible tribes of the Andaman and Nicobar islands,
      India, were investigated. The Nicobarese tribe was investigated in 1989 and 1999.
      The S gene from 65 HBV isolates was amplified by PCR and sequenced. Genotyping
      and serotyping were carried out on the basis of phylogenetic and amino acid
      analyses of S gene. All 20 Nicobarese-89 isolates, nine Onges-99 isolates and the
      single Andamanese-99 HBV isolate were classified as genotype D. Of the Nicobarese
      99 isolates, 32 (91.4 %) and three (8.6 %) were genotypes D and A, respectively.
      Per cent nucleotide identity between the S sequences representing different
      tribes varied from 98.06 to 98.59 % and varied from mainland isolates by 1.6-2.0
      %. Although southeast Asian origin is postulated for the Nicobarese tribe, the
      presence of different genotypes suggests introduction of HBV after migration to
      these islands, probably from mainland India, 200 years back, when these islands
      became inhabited as a part of penal settlement during the British regimen.

PMID- 12810888
TI  - Improved conformation-dependent immunoassay: suitability for human prion
      detection with enhanced sensitivity.
AB  - The presence of pathogenic prion protein (PrP(Sc)) in lymphoid tissues of variant
      Creutzfeldt-Jakob disease (vCJD) patients raises questions as to whether prions
      may be present in bodily fluids as well. Currently, transgenic mice are highly
      sensitive in vivo tools for the study of prions in tissues or fluids containing
      high levels of normal prion protein (PrP(C)). We report here an in vitro assay
      with virtually equivalent sensitivity incorporating a capture antibody into a
      sandwich conformation-dependent immunoassay (CDI), resulting in 30- to 100-fold
      increased sensitivity compared with the original, direct CDI. Furthermore,
      spiking plasma with vCJD prions in different preparations demonstrated that
      sandwich CDI detects prions with different biophysical properties at high
      sensitivity, even without proteinase K pretreatment of samples. Thus, sandwich
      CDI represents a powerful tool to study prions in bodily fluids of CJD/vCJD
      patients, with a turnaround time of less than 24 h.

PMID- 12810889
TI  - Prion diseases: infectious and lethal doses following oral challenge.
AB  - A brain homogenate prepared from a terminally ill hamster infected with scrapie
      strain 263K was serially diluted and administered orally to groups of hamsters.
      The undiluted brain homogenate led to clinical scrapie in all animals inoculated.
      The attack rate decreased with dilutions of the homogenate, and subclinical
      infections were identified among the healthy survivors at 520 days post-infection
      by Western blotting. The number of animals succumbing to disease and the combined
      number of Western blot-positive survivors plus diseased hamsters were used to
      calculate the LD(50) and ID(50) of the inoculum. The model system represents an
      approximation to the transmission of TSEs such as new variant Creutzfeldt-Jakob
      disease (vCJD) via dietary exposure to the infectious agent and suggests that,
      due to the rather small difference between the calculated LD(50) and ID(50), the
      number of clinical cases will not be vastly exceeded by the number of subclinical
      carriers of the disease.

PMID- 12810890
TI  - Interaction of replicase components between Cucumber mosaic virus and Peanut
      stunt virus.
AB  - Cucumber mosaic virus (CMV) and Peanut stunt virus (PSV) each have genomes
      consisting of three single-stranded RNA molecules: RNA 1, 2 and 3. RNAs 1 and 2
      encode the 1a and 2a proteins, respectively, which are necessary for replication
      of the viral genome. Although RNA 3 is exchangeable between CMV and PSV, exchange
      of RNA 1 and 2 between the two viruses has been unsuccessful. In this study,
      reassortants containing PSV RNA 1 and CMV RNA 2 together with RNA 3 of CMV or PSV
      were shown to be able to replicate their genomic RNA, but not to transcribe
      subgenomic RNA 4 in tobacco protoplasts. Conversely, the reassortant consisting
      of CMV RNA 1 and PSV RNA 2 together with RNA 3 of CMV or PSV could not replicate.
      Subsequently, a yeast two-hybrid system was used to analyse the in vivo
      interaction between the 1a and 2a proteins. The C-terminal half of PSV-1a protein
      interacted with the N-terminal region of 2a protein of both PSV and CMV, but the
      C-terminal half of CMV-1a and the N-terminal region of PSV-2a did not interact.
      These results suggest that RNA replication in the interspecific reassortant
      between CMV and PSV requires compatibility between the C-terminal half of the 1a
      protein and the N-terminal region of the 2a protein, and this compatibility is
      insufficient for transcription of subgenomic RNA 4.

PMID- 12810891
TI  - Should home screening tests for Alzheimer's disease be regulated?

PMID- 12810892
TI  - "Do-it-yourself" dementia testing: issues regarding an Alzheimer's home screening
      test.
AB  - The Early Alert Alzheimer's Home Screening Test (AHST) is a variant of the Smell
      Identification Test (SIT) and the Cross-Cultural Smell Identification Test (CC
      SIT), and recently became available for purchase by the general public. The
      validity and the practical utility of routine screening for individuals with
      asymptomatic cognitive impairment has not been established. There are
      considerable specific methodological concerns regarding the use of the AHST
      including the association of olfactory impairment with (a) age in the absence of
      cognitive impairment, (b) numerous acute and/or chronic medical conditions, and
      (c) lifestyle habits and social and/or demographic variables. General public
      misunderstanding of the difference between a screening and a diagnostic test,
      primary care physicians' frequent confusion about follow-up mechanisms for newly
      diagnosed patients with dementia, the possible lack of perceived counseling
      options for those self-diagnosed, and abuse of test findings create distinct
      possibilities for misuse of this test. The marketing of the AHST and its general
      use without appropriate public health educational safeguards is inappropriate and
      may be unethical.

PMID- 12810893
TI  - Differences in presenting advance directives in the chart, in the minimum data
      set, and through the staff's perceptions.
AB  - PURPOSE: Decisions concerning end-of-life care depend on information contained in
      advance directives that are documented in residents' charts in the nursing home.
      The availability of that information depends on the quality of the chart and on
      the location of the information in the chart. No research was found that compared
      directives by the manner in which they are collected and summarized in the chart.
      The goal of the proposed study was to clarify how advance directives are
      summarized in the patient's record and to clarify how physicians perceive the
      same advance directives and formal orders. DESIGN AND METHODS: The study involved
      122 elderly persons who reside in one large (587 beds) nursing home. The authors
      collected data regarding the advance directives from three sources-Minimum Data
      Set (MDS), the front cover of the resident's chart, and from inside the chart.
      RESULTS: The rates of documented advance directives found in this study are
      higher than those reported in the literature. Agreement rates between sources
      varied as a function of which sources were compared, as well as on the basis of
      which directive was examined. More specifically, the authors found higher rates
      of agreement between the information inside the chart and on the cover of the
      chart than between the MDS and the other two sources. IMPLICATIONS: The reasons
      for discrepancies may lie in the different functions and procedures pertaining to
      these source documents.

PMID- 12810895
TI  - The effect of age on the use of health and self-care information: confronting the
      stereotype.
AB  - PURPOSE: Given stereotypes of older adults, there is the perception that older
      adults will not use health information technologies. One concern is that
      practitioners might shy away from providing older patients with health
      information, and in particular, computerized information. The study's primary
      objective was to evaluate whether a health information intervention had a
      differential effect for people of different ages. DESIGN AND METHODS: Quasi
      experimental survey data from an assessment of a communitywide informational
      intervention were used. People were asked about their use of medical reference
      books, telephone advice nurses, or computers for health information in the past
      few months. In total, 5,909 surveys were completed. RESULTS: The data show that
      older adults were no less likely (and were sometimes more likely) to use health
      information as a result of the intervention than younger adults. For telephone
      advice nurses and computers, the effect of the intervention was not significantly
      different for the different age groups. Yet, compared with persons 18-29 years of
      age, those over the age of 65 had a 17-percentage point increase in using a self
      care book. IMPLICATIONS: We find convincing evidence to counter the stereotype
      that older adults are resistant to trying new health information technologies.

PMID- 12810896
TI  - Evaluating the effectiveness of a multimedia program on home safety.
AB  - PURPOSE: This study was designed to test the effectiveness and acceptance of
      multimedia home safety programming by community-dwelling seniors. DESIGN AND
      METHODS: A prototype CD-ROM was produced that required no reading or computer
      skills because the program included an audio narration of content and directions
      for operating the program on a touchscreen computer monitor. Volunteers (N = 126)
      from a senior center aged 55 and older were randomly assigned to (1) a multimedia
      group that used the interactive program to learn about home safety, (2) a
      traditional learning group that read well-established booklets on home safety,
      and (3) a control group that received no instruction on safety between the pre-
      and posttests. RESULTS: Repeated-measures multivariate analysis of variance
      showed that the multimedia group was the only group to improve in knowledge. The
      group was also very satisfied with the approach. IMPLICATIONS: Multimedia formats
      can effectively and economically provide information to older clients.

PMID- 12810894
TI  - Advance care planning in nursing homes: correlates of capacity and possession of
      advance directives.
AB  - PURPOSE: The identification of nursing home residents who can continue to
      participate in advance care planning about end-of-life care is a critical
      clinical and bioethical issue. This study uses high quality observational
      research to identify correlates of advance care planning in nursing homes,
      including objective measurement of capacity. DESIGN AND METHODS: The authors used
      cross-sectional, cohort study between 1997 and 1999. Seventy-eight residents (M
      age = 83.97, SD = 8.2) and their proxies (M age = 59.23, SD = 11.77) were
      included across five nursing homes. The authors obtained data via chart review,
      proxy interviews, resident assessments, survey completion by certified nursing
      assistants, and direct observation of residents' daily behaviors. RESULTS:
      Capacity assessments revealed that most residents could state a simple treatment
      preference (82.4%), but a sizable number did not retain capacity to understand
      treatment alternatives or appreciate the consequences of their choice. Global
      cognitive ability (Mini-Mental State Examination score) was related to
      understanding and appreciation. When the authors removed the effects of global
      cognitive ability, understanding and appreciation were related to time spent by
      residents in verbal interaction with others. Residents were more likely to
      possess advance directives when proxies possessed advance directives, proxies
      were less religious, and residents were socially engaged. IMPLICATIONS:
      Assessment of proxy beliefs and direct determination of residents' decisional
      capacity and social engagement may help nursing home staff identify families who
      may participate in advance planning for end-of-life medical care. Measures of
      global cognitive ability offer limited information about resident capacity for
      decision making. Decisional capacity assessments should enhance the verbal
      ability of individuals with dementia by reducing reliance on memory in the
      assessment process. Interventions to engage residents and families in structured
      discussions for end-of-life planning are needed.

PMID- 12810897
TI  - A comparison of assistive technology and personal care in alleviating disability
      and unmet need.
AB  - PURPOSE: The authors examine differences in reports of residual disability and
      unmet need by type of long-term care arrangement (assistive technology or
      personal care). DESIGN AND METHODS: This study compares three specific dimensions
      of residual difficulty (pain, fatigue, and time intensity) and reports of unmet
      need across care arrangements. Samples from the U. S. 1994-1995 National Health
      Interview Survey Phase 2 Disability Supplements include adults with limitations
      in bathing, transferring, walking, and getting outside. RESULTS: Even when
      differences in underlying disability are accounted for, assistive technology (AT)
      confers no additional benefit in the three dimensions of residual difficulty
      analyzed here. AT users equally or more often report that tasks are tiring, time
      consuming, or painful, even when they use assistance. Though this would appear to
      indicate unmet needs for care, fewer AT users report a desire for hands-on
      personal care. IMPLICATIONS: Though disability alleviation by technology is no
      better on specific dimensions of difficulty, technology users report less unmet
      need for personal care. Designing appropriate and cost-effective home care for
      adults with disabilities requires a better understanding of the ways in which
      technology users may differ from others and the circumstances under which
      technology can be most effective.

PMID- 12810898
TI  - Total and out-of-pocket expenditures for prescription drugs among older persons.
AB  - PURPOSE: The burden of prescription drug costs on Medicare beneficiaries has
      become a critical policy issue in improving the Medicare program, yet few studies
      have provided detailed and current information on that burden. The present study
      estimates total and out-of-pocket expenditures for prescription drugs and the
      burden of these costs in relation to income among the elderly population. We also
      compare spending and burden across major subgroups of the elderly population, as
      defined by socioeconomic and health characteristics, and we distinguish the
      impact of these factors by using multivariate models. DESIGN AND METHODS: The
      study uses nationally representative data on Medicare beneficiaries from the 1997
      Medicare Current Beneficiary Survey Cost and Use files. The study estimates out
      of-pocket prescription drug spending and burden through ordinary least square,
      median, and logistic regression models with corrections for the complex survey
      design. RESULTS: Our results show that in 1997, nearly 8% of the older
      population, more than 2.3 million people, spent greater than 10% of their income
      on prescription drugs. Despite pharmacy coverage, out-of-pocket cost burden fell
      most heavily on women and those with chronic health conditions. Burden was also
      higher among those with self-purchased supplemental coverage. IMPLICATIONS: The
      impact of Medicare reform proposals on these subgroups has to be carefully
      evaluated.

PMID- 12810899
TI  - Development of the family caregiver medication administration hassles scale.
AB  - PURPOSE: "Medication administration hassles" are the minor daily irritants that
      family caregivers experience when they assist a dependent family member with
      medication regimens. This study was designed to develop and test a
      multidimensional measure of the hassles in family caregiver medication
      administration. DESIGN AND METHOD: The authors employed a multiphase process
      (caregiver focus groups, instrument development, pilot testing, and field
      testing). Approximately 180 family caregivers representing diverse socioeconomic
      circumstances and racial or ethnic backgrounds participated in the study. The
      final version of the instrument consists of 24 items and four subscales:
      Information Seeking/Information Sharing (9 items, alpha =.92), Safety Issues (5
      items, alpha =.83), Scheduling Logistics (7 items, alpha =.90), and Polypharmacy
      (3 items, alpha =.80). Overall scale reliability is.95, and test-retest
      reliability at 2 weeks is.84. IMPLICATIONS: Caregiver medication administration
      hassles represent a complex, multidimensional construct that warrants
      consideration in studies of contemporary family caregiver stress, strain, and
      burden.

PMID- 12810900
TI  - Self-rated health, gender, and mortality in older persons: introduction to a
      special section.

PMID- 12810902
TI  - Concepts of self-rated health: specifying the gender difference in mortality
      risk.
AB  - PURPOSE: This study addresses the question of how the relation between self-rated
      health (SRH) and mortality differs between genders. In addition to the general
      question, four specific concepts of SRH are distinguished: SRH in comparison with
      age peers, SRH in comparison with one's own health 10 years ago, and current and
      future health perceptions. For these concepts, the gender-specific risks of
      mortality were evaluated for a short and a longer follow-up period. DESIGN AND
      METHODS: Baseline and mortality data from the Longitudinal Aging Study Amsterdam
      (N = 1917, initial ages 55-85 years) were used. Mortality risks were evaluated in
      Cox regression models at 3 and 7.5 years of follow-up, both adjusted for age and
      for sociodemographic characteristics, indicators of functional and mental health,
      lifestyle, and social involvement. All SRH measures were scaled from 1 (positive)
      to 5 (negative). RESULTS: Baseline correlations between SRH concepts were similar
      for men and women. After 3 years, 12% of the men and 7% of the women had died;
      after 7.5 years, these percentages were 27 and 15, respectively. In fully
      adjusted models, current health perceptions predicted 3-year mortality in men
      (risk ratio of 1.33). At 7.5 years, mortality in men was predicted by current
      health perceptions and by SRH compared with age peers (risk ratios of 1.25 and
      1.23, respectively). In women, no SRH concept predicted either 3-year or 7.5-year
      mortality. IMPLICATIONS: SRH was a predictor of mortality only in men, not in
      women. The gender difference showed most clearly at longer follow-up, in the SRH
      concept "comparison with age peers."

PMID- 12810903
TI  - Differences between older men and women in the self-rated health-mortality
      relationship.
AB  - PURPOSE: The aims of this study were to examine differences between older men and
      women: (a) in the ability of self-rated health to predict mortality, (b) in the
      effect of different follow-up periods on the self-rated health mortality
      relationship, and (c) in the relative importance of self-rated health and self
      rated change in health in predicting mortality. DESIGN AND METHODS: By using data
      from the Nottingham Longitudinal Study of Activity and Ageing, the author
      assessed relationships between self-rated health and self-rated change in health
      and 4- and 12-year mortality in separate unadjusted and adjusted Cox proportional
      hazards regression models in men and women. RESULTS: The differences between men
      and women in the hazard ratios for poor self-rated health were not significant,
      although there were differences in the explanatory factors. The relationship
      between self-rated health and short-term and long-term mortality was explained by
      age and health among men. The relationship between self-rated health and short
      term mortality was explained by age, physical and mental health, and physical
      activity among women. The relationship between self-rated health and long-term
      mortality was explained by age, physical health, and physical activity among
      women. The relationship between self-rated change in health and short-term
      mortality was explained by age among men and women. The relationship between self
      rated change in health and long-term mortality was explained by age and physical
      health among men and women. Social engagement was an independent predictor of
      short- and long-term mortality among men and women in this study. IMPLICATIONS:
      The finding that low self-rated health was not an independent predictor of
      mortality among men or women, contrary to many, but not all, previous studies,
      may be related to differences in study design and/or across cultures. Further
      research investigating relationships between self-rated health and mortality and
      potential explanatory variables should analyze men and women separately and
      should consider the length of follow-up period. The benefits of individual
      physical and social activities in reducing mortality merit further investigation.

PMID- 12810904
TI  - Gender differences in the self-rated health-mortality association: is it poor
      self-rated health that predicts mortality or excellent self-rated health that
      predicts survival?
AB  - PURPOSE: This study investigates gender differences in the association between
      self-rated health (SRH) and mortality. This association has been well-documented,
      but findings regarding gender differences are inconsistent. The specific
      objectives were (a) to examine these differences in a short and a long time
      frame, (b) to examine these differences among old and old-old people, and (c) to
      address the question of whether this association is based on the accuracy of poor
      SRH as a predictor of future decline, and/or of better SRH as a predictor of
      longevity. DESIGN AND METHODS: The study is based on an Israeli nationally
      representative sample of 622 women and 730 men who were interviewed about their
      SRH, as well as sociodemographic information and other measures of health,
      physical functioning, cognitive status, and depression. RESULTS: For both
      genders, SRH was associated only with shorter term mortality (within the next 4
      years) and not with longer-term mortality (9 years of follow-up). This
      association was strongest among the old (ages 75-84) women, compared with the old
      men and with the old-old (85-94) women and men. A possible explanation may be
      related to differences in the accuracy of excellent SRH at very old age.
      IMPLICATIONS: The SRH-mortality association may differ among age and gender
      groups. Identifying the conditions under which it is more accurate will enable
      researchers and practitioners to know when it can be utilized. It is important to
      assess differences in the accuracy of poor SRH as well as of excellent SRH as
      predictors of future health outcomes.

PMID- 12810905
TI  - Are gender differences in the relationship between self-rated health and
      mortality enduring? Results from three birth cohorts in Melton Mowbray, United
      Kingdom.
AB  - PURPOSE: The purpose of this study was to assess whether there is an enduring
      gender difference in the ability of self-rated health to predict mortality and
      investigate whether self-reported physical health problems account for this
      difference. DESIGN AND METHODS: Cox models for 4-year survival were fitted to
      data from successive cohorts aged 75-81 years registered with a primary care
      practice in the U.K. Midlands surveyed in 1981, 1988, and 1993-1995. RESULTS:
      Self-rated health was consistently a stronger predictor in men (hazard ratio [HR]
      = 2.7; 95% confidence interval [CI] = 2.1-3.5) than it was in women (HR = 1.9;
      95% CI = 1.5-2.4). Women surveyed in 1993-1995 were more likely than men to
      report problems that were disabling but not life-threatening, whereas men were
      more likely to report potentially life-threatening problems. However, these
      differences did not explain the association of self-rated health with mortality.
      More than half of those who reported a potentially life-threatening problem said
      that their health was good. IMPLICATIONS: Self-rated health is more strongly
      associated with mortality in men, but this is unlikely to be explained by
      differences in the nature of their physical health problems.

PMID- 12810910
TI  - A snoRNA that guides the two most conserved pseudouridine modifications within
      rRNA confers a growth advantage in yeast.
AB  - Ribosomal RNAs contain a number of modified nucleotides. The most abundant
      nucleotide modifications found within rRNAs fall into two types: 2'-O-ribose
      methylations and pseudouridylations. In eukaryotes, small nucleolar guide RNAs,
      the snoRNAs that are the RNA components of the snoRNPs, specify the position of
      these modifications. The 2'-O-ribose methylations and pseudouridylations are
      guided by the box C/D and box H/ACA snoRNAs, respectively. The role of these
      modifications in rRNA remains poorly understood as no clear phenotype has yet
      been assigned to the absence of specific 2'-O-ribose methylations or
      pseudouridylations. Only very recently, a slight translation defect and
      perturbation of polysome profiles was reported in yeast for the absence of the
      Psi at position 2919 within the LSU rRNA. Here we report the identification and
      characterization in yeast of a novel intronic H/ACA snoRNA that we called snR191
      and that guides pseudouridylation at positions 2258 and 2260 in the LSU rRNA.
      Most interestingly, these two modified bases are the most conserved
      pseudouridines from bacteria to human in rRNA. The corresponding human snoRNA is
      hU19. We show here that, in yeast, the presence of this snoRNA, and hence, most
      likely, of the conserved pseudouridines it specifies, is not essential for
      viability but provides a growth advantage to the cell.

PMID- 12810911
TI  - In vitro selection for sense codon suppression.
AB  - The universal genetic code links the 20 naturally occurring amino acids to the 61
      sense codons. Previously, the UAG amber stop codon (a nonsense codon) has been
      used as a blank in the code to insert natural and unnatural amino acids via
      nonsense suppression. We have developed a selection methodology to investigate
      whether the unnatural amino acid biocytin could be incorporated into an mRNA
      display library at sense codons. In these experiments we probed a single
      randomized NNN codon with a library of 16 orthogonal, biocytin-acylated tRNAs. In
      vitro selection for efficient incorporation of the unnatural amino acid resulted
      in templates containing the GUA codon at the randomized position. This sense
      suppression occurs via Watson-Crick pairing with similar efficiency to UAG
      mediated nonsense suppression. These experiments suggest that sense codon
      suppression is a viable means to expand the chemical and functional diversity of
      the genetic code.

PMID- 12810912
TI  - DnaK-facilitated ribosome assembly in Escherichia coli revisited.
AB  - Assembly helpers exist for the formation of ribosomal subunits. Such a function
      has been suggested for the DnaK system of chaperones (DnaK, DnaJ, GrpE). Here we
      show that 50S and 30S ribosomal subunits from an Escherichia coli dnaK-null
      mutant (containing a disrupted dnaK gene) grown at 30 degrees C are physically
      and functionally identical to wild-type ribosomes. Furthermore, ribosomal
      components derived from mutant 30S and 50S subunits are fully competent for in
      vitro reconstitution of active ribosomal subunits. On the other hand, the DnaK
      chaperone system cannot circumvent the necessary heat-dependent activation step
      for the in vitro reconstitution of fully active 30S ribosomal subunits. It is
      therefore questionable whether the requirement for DnaK observed during in vivo
      ribosome assembly above 37 degrees C implicates a direct or indirect role for
      DnaK in this process.

PMID- 12810913
TI  - Aminoacylation of an unusual tRNA(Cys) from an extreme halophile.
AB  - The extreme halophile Halobacterium species NRC-1 overcomes external near
      saturating salt concentrations by accumulating intracellular salts comparable to
      those of the medium. This raises the fundamental question of how halophiles can
      maintain the specificity of protein-nucleic acid interactions that are
      particularly sensitive to high salts in mesophiles. Here we address the
      specificity of the essential aminoacylation reaction of the halophile, by
      focusing on molecular recognition of tRNA(Cys) by the cognate cysteinyl-tRNA
      synthetase. Despite the high salt environments of the aminoacylation reaction,
      and despite an unusual structure of the tRNA with an exceptionally large
      dihydrouridine loop, we show that aminoacylation of the tRNA proceeds with a
      catalytic efficiency similar to that of its mesophilic counterparts. This is
      manifested by an essentially identical K(m) for tRNA to those of the mesophiles,
      and by recognition of the same nucleotide determinants that are conserved in
      evolution. Interestingly, aminoacylation of the halophile tRNA(Cys) is more
      closely related to that of bacteria than eukarya by placing a strong emphasis on
      features of the tRNA tertiary core. This suggests an adaptation to the highly
      negatively charged tRNA sugar-phosphate backbone groups that are the key elements
      of the tertiary core.

PMID- 12810914
TI  - An siRNA ribonucleoprotein is found associated with polyribosomes in Trypanosoma
      brucei.
AB  - Genetic interference by double-stranded RNA (dsRNA) or RNA interference (RNAi)
      triggers the sequence-specific degradation of cellular transcripts. The mediators
      of mRNA degradation are small interfering RNAs (siRNAs). Here, we report that in
      Trypanosoma brucei, 10%-20% of siRNAs cosediment with polyribosomes. Preventing
      the assembly of ribosomes on mRNAs results in a concomitant decrease of siRNAs
      sedimenting as high-molecular-weight complexes. We further provide evidence that
      siRNAs are associated with translating ribosomes and that this association is
      mediated by a 70-kD ribonucleoprotein complex.

PMID- 12810915
TI  - The dynamic nature of the four-way junction of the hepatitis C virus IRES.
AB  - Translation is initiated within the RNA of the hepatitis C virus at the internal
      ribosome entry site (IRES). The IRES is a 341-nucleotide element that contains a
      four-way helical junction (IIIabc) as a functionally important element of the
      secondary structure. The junction has three additional, nonpaired nucleotides at
      the point of strand exchange on one diagonal. We have studied the global
      conformation and folding of this junction in solution, using comparative gel
      electrophoresis and steady-state and time-resolved fluorescence resonance energy
      transfer. In the absence of divalent metal ions, the junction adopts an extended
      square structure, in contrast to perfect four-way RNA junctions, which retain
      coaxial helical stacking under all conditions. The IIIabc junction is induced to
      fold on addition of Mg(2+), by pairwise coaxial stacking of arms, into the
      conformer in which the unpaired bases are located on the exchanging strands.
      Fluorescence lifetime measurements indicate that in the presence of Mg(2+) ions,
      the IIIabc junction exists in a dynamic equilibrium comprising approximately
      equal populations of antiparallel and parallel species. These dynamic properties
      may be important in mediating interactions between the IRES and the ribosome and
      initiation factors.

PMID- 12810916
TI  - A structural, phylogenetic, and functional study of 15.5-kD/Snu13 protein binding
      on U3 small nucleolar RNA.
AB  - The 15.5-kD protein and its yeast homolog Snu13p bind U4 snRNA, U3 snoRNA, and
      the C/D box snoRNAs. In U4 snRNA, they associate with a helix-bulge-helix (K
      turn) structure. U3 snoRNA contains two conserved pairs of boxes, C'/D and B/C,
      which were both expected to bind the 15.5-kD/Snu13 protein. Only binding to the
      B/C motif was experimentally demonstrated. Here, by chemical probing of in vitro
      reconstituted RNA/protein complexes, we demonstrate the independent binding of
      the 15.5-kD/Snu13 protein to each of the two motifs. Due to a highly reduced stem
      I (1 bp), the K-turn structure is not formed in the naked B/C motif. However, gel
      shift experiments revealed a higher affinity of Snu13p for the B/C motif,
      compared to the C'/D motif. A phylogenetic analysis of U3 snoRNA, coupled with an
      analysis of Snu13p affinity for variant yeast C'/D and B/C motifs, and a study of
      the functionality of a truncated yeast U3 snoRNA carrying base substitutions in
      the C'/D and B/C motifs, revealed that conservation of the identities of residues
      2 and 3 in the B/C K-turn is more important for Snu13p binding and U3 snoRNA
      function, than conservation of the identities of corresponding residues in the
      C'/D K-turn. This suggests that binding of Snu13p to K-turns with a very short
      helix I imposes sequence constraints in the bulge. Altogether, the data
      demonstrate the strong importance of the binding of the 15.5-kD/Snu13 protein to
      the C'/D and B/C motifs for both U3 snoRNP assembly and activity.

PMID- 12810917
TI  - Biochemical analysis and scanning force microscopy reveal productive and
      nonproductive ADAR2 binding to RNA substrates.
AB  - Scanning force microscopy (SFM) can be used to image biomolecules at high
      resolution. Here we demonstrate that single-molecule analysis by SFM complements
      biochemical data on RNA protein binding and can provide information that cannot
      be obtained by the usual biochemical methods. We have used this method to study
      the interaction between the RNA editing enzyme ADAR2 and RNA transcripts
      containing selective and nonselective editing sites. The natural selectively
      edited R/G site from glutamate receptor subunit B (GluR-B) was inserted into an
      RNA backbone molecule consisting of a completely double-stranded (ds) central
      part and incompletely paired ends derived from potato spindle tuber viroid
      (PSTVd). This molecule was efficiently edited at the R/G site, but promiscuous
      editing occurred at nonselective sites in the completely double-stranded region.
      The construct was also used to analyze binding of ADAR2 to wild-type and modified
      R/G editing sites in relation to binding at other nonselectively edited sites.
      Editing analysis together with SFM allow us to differentiate between binding and
      enzymatic activity. ADAR2 has been reported to have a general affinity to dsRNA.
      However, we show that there is a prominent bias for stable binding at sites
      selectively edited over other edited sites. On the other hand, promiscuous
      editing at nonselective sites apparently results from transient binding of the
      enzyme to the substrate. Furthermore, we find distinct sites with nonproductive
      binding of the enzyme.

PMID- 12810918
TI  - UAP56 levels affect viability and mRNA export in Caenorhabditis elegans.
AB  - Expression of a gfp transgene in the intestines of living Caenorhabditis elegans
      has been measured following depletion by RNAi of a variety of known splicing
      factors and mRNA export proteins. Reduction of most splicing factors showed only
      a small effect on expression of the transgene in the animal injected with dsRNA,
      although most of these RNAi's resulted in embryonic lethality in their offspring.
      In contrast, RNAi of nxf-1, the worm homolog of mammalian NXF1/TAP, a key
      component of the mRNA export machinery, resulted in dramatic suppression of GFP
      expression in the injected animals. When we tested other proteins previously
      reported to be involved in marking mRNAs for export, we obtained widely divergent
      results. Whereas RNAi of the worm REF/Aly homologs had no obvious effect, either
      in the injected animals or their offspring, RNAi of UAP56, reported to be the
      partner of REF/Aly, resulted in strong suppression of GFP expression due to
      nuclear retention of its mRNA. Overexpression of UAP56 also resulted in rapid
      loss of GFP expression and lethality at all stages of development. We conclude
      that UAP56 plays a key role in mRNA export in C. elegans, but that REF/Aly may
      not. It also appears that some RNA processing factors are required for viability
      (e.g., U2AF, PUF60, SRp54, SAP49, PRP8, U1-70K), whereas others are not (e.g.,
      U2A', CstF50).

PMID- 12810919
TI  - Inhibition of the protein kinase PKR by the internal ribosome entry site of
      hepatitis C virus genomic RNA.
AB  - Translation of the hepatitis C genome is mediated by internal ribosome entry on
      the structurally complex 5' untranslated region of the large viral RNA.
      Initiation of protein synthesis by this mechanism is independent of the cap
      binding factor eIF4E, but activity of the initiator Met-tRNA(f)-binding factor
      eIF2 is still required. HCV protein synthesis is thus potentially sensitive to
      the inhibition of eIF2 activity that can result from the phosphorylation of the
      latter by the interferon-inducible, double-stranded RNA-activated protein kinase
      PKR. Two virally encoded proteins, NS5A and E2, have been shown to reduce this
      inhibitory effect of PKR by impairing the activation of the kinase. Here we
      present evidence for a third viral strategy for PKR inhibition. A region of the
      viral RNA comprising part of the internal ribosome entry site (IRES) is able to
      bind to PKR in competition with double-stranded RNA and can prevent
      autophosphorylation and activation of the kinase in vitro. The HCV IRES itself
      has no PKR-activating ability. Consistent with these findings, cotransfection
      experiments employing a bicistronic reporter construct and wild-type PKR indicate
      that expression of the protein kinase is less inhibitory towards HCV IRES-driven
      protein synthesis than towards cap-dependent protein synthesis. These data
      suggest a dual function for the viral IRES, with both a structural role in
      promoting initiation complex formation and a regulatory role in preventing
      inhibition of initiation by PKR.

PMID- 12810920
TI  - RNA-binding activity of translation initiation factor eIF4G1 from Saccharomyces
      cerevisiae.
AB  - We identified and mapped RNA-binding sites of yeast Saccharomyces cerevisiae
      translation initiation factor eIF4G1 and examined their importance for eIF4G1
      function in vitro and in vivo. Yeast eIF4G1 binds to single-stranded RNA with
      three different sites, the regions of amino acids 1-82 (N terminus), 492-539
      (middle), and 883-952 (C terminus). The middle and C-terminal RNA-binding sites
      represent RS (arginine and serine)-rich domains; the N-terminal site is
      asparagine-, glutamine- and glycine-rich. The three RNA-binding sites have
      similar affinity for single-stranded RNA, whereas the affinity for single
      stranded RNA full-length eIF4G1 is about 100-fold higher (approximate K(d) of 5 x
      10(-8) M). Replacement of the arginine residues in the middle RS site by alanine
      residues abolishes its RNA-binding activity. Deletion of individual RNA-binding
      sites shows that eIF4G1 molecules lacking one binding site are still active in
      supporting growth of yeast cells and translation in vitro, whereas eIF4G1
      molecules lacking two or all three RNA-binding sites are strongly impaired or
      inactive. These data suggest that RNA-binding activity is required for eIF4G1
      function.

PMID- 12810921
TI  - The Ref/Aly proteins are dispensable for mRNA export and development in
      Caenorhabditis elegans.
AB  - The mRNA export pathway is highly conserved throughout evolution. We have used
      RNA interference (RNAi) to functionally characterize bona fide RNA export factors
      and components of the exon-exon junction complex (EJC) in Caenorhabditis elegans.
      RNAi of CeNXT1/p15, the binding partner of CeNXF1/TAP, caused early embryonic
      lethality, demonstrating an essential function of this gene during C. elegans
      development. Moreover, depletion of this protein resulted in nuclear accumulation
      of poly(A)(+) RNAs, supporting a direct role of NXT1/p15 in mRNA export in C.
      elegans. Previously, we have shown that RNAi of CeSRm160, a protein of the EJC
      complex, resulted in wild-type phenotype; in the present study, we demonstrate
      that RNAi of CeY14, another component of this complex, results in embryonic
      lethality. In contrast, depletion of the EJC component CeRNPS1 results in no
      discernible phenotype. Proteins of the REF/Aly family act as adaptor proteins
      mediating the recruitment of the mRNA export factor, NXF1/TAP, to mRNAs. The C.
      elegans genome encodes three members of the REF/Aly family. RNAi of individual
      Ref genes, or codepletion of two Ref genes in different combinations, resulted in
      wild-type phenotype. Simultaneous suppression of all three Ref genes did not
      compromise viability or progression through developmental stages in the affected
      progeny, and only caused a minor defect in larval mobility. Furthermore, no
      defects in mRNA export were observed upon simultaneous depletion of all three REF
      proteins. These results suggest the existence of multiple adaptor proteins that
      mediate mRNA export in C. elegans.

PMID- 12810923
TI  - Increased prevalence of dental caries and poor oral hygiene in juvenile
      idiopathic arthritis.
AB  - OBJECTIVES: Recent decades have seen a trend to treat juvenile idiopathic
      arthritis (JIA) with increasing immunosuppression to improve the long-term
      outcome. Poor oral hygiene and dental decay cause significant morbidity, and
      patients with chronic disease (who may be further immunocompromised by treatment)
      are at greater risk. This study investigated patients with JIA using standard
      measures of oral health. METHODS: One hundred and forty-nine patients with JIA
      were included. The children were attending a regional paediatric rheumatology
      service and the adults were attending an adult rheumatology clinic. Random age-
      and sex-matched healthy controls were recruited from a dental teaching hospital.
      The structured dental examination included standard epidemiological indices of
      oral hygiene (gingival index, plaque index, oral cleanliness index) and dental
      decay [DMFT (decayed, missing or filled teeth) index]. RESULTS: JIA patients, at
      all ages, had increased levels of dental decay and poor oral hygiene. This
      increased level of decay was statistically significant in the patients aged 0-11
      yr. Significant levels of untreated caries and increased levels of missing teeth
      were found in JIA, suggesting that patients with JIA had less restorative dental
      treatment, with tooth extraction often the chosen option for the treatment of
      dental decay. CONCLUSIONS: This is the largest study of oral health in JIA and is
      cross-sectional with non-diseased controls. It shows significantly increased
      levels of poor oral hygiene and dental decay in patients with JIA. The high
      levels of untreated dental decay suggest barriers to dental care. These results
      emphasize the role of regular dental care in the multidisciplinary management of
      JIA.

PMID- 12810922
TI  - Characterization of the catalytic activity of U2 and U6 snRNAs.
AB  - Removal of introns from pre-messenger RNAs in eukaryotes is carried out by the
      spliceosome, an assembly of a large number of proteins and five small nuclear
      RNAs (snRNAs). We showed previously that an in vitro transcribed and assembled
      base-paired complex of U2 and U6 snRNA segments catalyzes a reaction that
      resembles the first step of splicing. Upon incubation with a short RNA
      oligonucleotide containing the consensus sequence of the pre-mRNA branch site,
      the U2/U6 complex catalyzed a reaction between the 2' OH of a bulged adenosine
      and a phosphate in the catalytically important AGC triad of U6, leading to the
      formation of an X-shaped product, RNA X, apparently linked by an unusual
      phosphotriester bond. Here we characterize this splicing-related reaction
      further, showing that RNA X formation is an equilibrium reaction, and that the
      low yield of the reaction likely reflects an unfavorable equilibrium coefficient.
      Consistent with a phosphotriester linkage, RNA X is highly alkali-sensitive, but
      only mildly acid-sensitive. We also show that mutations in the AGC sequence of U6
      can have significant effects on RNA X formation, further extending the
      similarities between splicing and RNA X formation. We also demonstrate that
      pseudouridylation of U2 enhances RNA X formation, and that U6 snRNA purified from
      nuclear extracts is capable of forming RNA X. Our data suggest that the ability
      to form RNA X might be an intrinsic property of spliceosomal snRNAs.

PMID- 12810924
TI  - Radiographic progression in early rheumatoid arthritis: a 12-month randomized
      controlled study comparing the combination of cyclosporin and methotrexate with
      methotrexate alone.
AB  - OBJECTIVE: To determine whether patients with early rheumatoid arthritis (RA)
      treated with cyclosporin A (CsA) and methotrexate (MTX) in combination for 12
      months show a lower rate of radiographic deterioration than those treated with
      MTX alone. METHODS: In this controlled and randomized single-blind trial, 61
      consecutive patients with untreated RA of less than 2 yr duration were treated
      with either CsA + MTX combination therapy (n = 30) or MTX alone (n = 31). The
      primary end-point was radiographic progression after 12 months, measured using
      the damage score (DS) of the Sharp and van der Heijde method. RESULTS: Although
      there was a significant difference between the mean baseline and 12-month DS in
      both treatment groups (MTX/CsA, 1.93 +/- 0.90; MTX, 7.47 +/- 2.03), it was
      significantly less in the combination arm (P = 0.018). Of the 30 evaluable CsA +
      MTX patients, 16 (53%) were ACR20 responders, 15 (50%) ACR50 and 14 (47%) ACR70;
      the corresponding figures in the MTX arm were 19 (61%), 13 (44%) and 6 (19%).
      Toxicity was acceptable in both groups. CONCLUSIONS: In patients with early RA,
      CsA + MTX combination therapy led to a significantly lower rate of 12-month
      radiographic progression, was effective on inflammatory articular symptoms, and
      was well tolerated.

PMID- 12810925
TI  - CARD15/NOD2 analysis in rheumatoid arthritis susceptibility.
AB  - OBJECTIVE: To determine if the mutations in the CARD15/NOD2 gene predisposing to
      Crohn's disease (CD) contribute also to the genetic susceptibility to rheumatoid
      arthritis (RA). METHODS: The frequencies of the three commonest mutations of
      CARD15/NOD2 predisposing to CD (2104C > T, 2722G>C and 3020insC) were determined
      in 210 RA patients and 227 controls. RESULTS: Allelic frequencies of the
      CARD15/NOD2 mutations in RA patients (2104C>T, 2.8%; 2722G>C, 0.9%; and 3020insC,
      2.4%) did not differ significantly from the controls (2104C>T, 5.3%; 2722G>C,
      0.7%; and 3020insC, 1.1%). CONCLUSION: There was no evidence of association
      between the commonest CD CARD15/NOD2 mutations and RA susceptibility.

PMID- 12810926
TI  - Definition and treatment of lupus flares measured by the BILAG index.
AB  - OBJECTIVES: The BILAG index is a clinical measure of lupus disease activity. It
      is valid, reliable and sensitive to change. Scoring in the BILAG index is based
      upon the physician's intention to treat. A flare of active lupus is defined as a
      new A or B score in at least one system. The main aim of this study was to
      determine whether patients with a lupus flare are treated as expected from the
      principles upon which the scoring system was devised. Secondly we wanted to
      establish whether patients with a new B score preceded by a C should be
      considered to have flared, as with patients scoring B following a D or E score.
      METHODS: Over a 12-month period, 250 patients regularly attending lupus clinics
      in Birmingham and London were assessed using the BILAG index at each visit.
      RESULTS: A new A or B score was observed in 154 (61.6%) patients. An A flare was
      observed in 26 (10.4%) patients. A B flare (in which the B score was preceded by
      a D or E score) was observed in 65 (26.0%) patients. There were 63 (25.2%)
      patients in whom there was a B score in a system in which a C score was
      previously recorded. Steroids were started or increased in 20 (77%) patients with
      an A flare. Almost all (92%) patients with a new A score had some increase in
      therapy. For the patients with new B scores, 53 (41%) had some increase in
      therapy, but multiple reasons were found for no change in therapy in 75 (59%) of
      these patients. There was no difference in the treatment of new B scores arising
      after a previous C score compared with previous D or E scores. Non-Caucasians
      were more likely to have a lupus flare than Caucasians. CONCLUSIONS: These
      results are consistent with the principles upon which the BILAG index was devised
      and suggest that a moderate disease flare can be defined as a new B score
      following a C, D or E score according to the BILAG index.

PMID- 12810927
TI  - Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production
      by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice.
AB  - OBJECTIVE: To clarify the pharmacological action of an anti-rheumatic agent T
      614, we investigated its effects on immunoglobulin (Ig) production by cultured B
      cells and Ig secretion from synovial tissues of patients with rheumatoid
      arthritis (RA) using SCID mice engrafted with human RA tissue (SCID-HuRAg).
      METHODS: Murine B cells were prepared from mouse spleen by a T-cell depletion
      method. The cells were cultured with lipopolysaccharide (LPS) and/or interleukin
      4 (IL-4) in the absence or presence of T-614. Human B cells were isolated from
      peripheral blood of healthy donors and the Ig production was induced by co
      culture with autologous T cells and anti-CD3 antibody. SCID-HuRAg was prepared
      according to our previous method. T-614 was orally administered to the mice once
      daily for 4 weeks starting on the fourth week after the implantation. Then,
      peripheral blood was obtained and the implanted tissues were removed. Igs in the
      culture media or the sera were determined by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: In murine B-cell cultures, T-614 significantly decreased not
      only the IgM production stimulated with LPS but IgG1 production induced by LPS
      and IL-4. Regarding human B cells stimulated with T cells, it also inhibited IgM
      and IgG production. In SCID-HuRAg mice, high concentrations of polyclonal human
      IgG were detectable in the sera of all mice. A significant decrease in the IgG
      level was observed in the T-614-treated group compared with the control group.
      CONCLUSIONS: We showed that T-614 inhibited Ig production by the cultured B cells
      and also decreased the high level of human IgG observed in SCID-HuRAg mice. These
      results may support its effect on plasma Ig in RA patients and provide insights
      into the mechanisms of its anti-rheumatic effect.

PMID- 12810928
TI  - Does psychological vulnerability determine health-care utilization in
      fibromyalgia?
AB  - OBJECTIVES: Patients with fibromyalgia (FM) undergo multiple testing and referral
      to specialists, and often use complementary/alternative medicine (CAM) services.
      The objectives of the study were: (i) to document health service utilization, and
      (ii) to examine whether psychological vulnerability was associated with visits to
      physicians and CAM providers. METHODS: Women (N = 178) with a diagnosis of
      primary FM completed a psychosocial test measuring pain, perceived stress, global
      psychological distress, sexual abuse history, co-morbidity and disability due to
      FM. Subjects also completed a health services questionnaire, documenting visits
      to physicians and CAM providers during the previous 6 months. Psychological
      vulnerability was operationalized as obtaining high scores on psychological
      distress, perceived stress and reporting at least one abusive event. RESULTS: The
      average number of visits was 7.2 to physicians and 11.3 to CAM providers.
      CONCLUSIONS: The number of physician visits was significantly associated with
      more co-morbidity. Psychologically vulnerable subjects were more likely to use
      CAM services than those not so classified.

PMID- 12810929
TI  - Comparison of the incidence rates of selected gastrointestinal events reported
      for patients prescribed celecoxib and meloxicam in general practice in England
      using prescription-event monitoring (PEM) data.
AB  - BACKGROUND: Celecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2
      selective inhibitors, and were developed to minimize the risk of gastrointestinal
      (GI) toxicity commonly associated with non-steroidal anti-inflammatory drugs
      (NSAIDs). The Drug Safety Research Unit (DSRU) monitored the safety of these
      drugs immediately after launch in England using the non-interventional
      observational cohort technique of prescription-event monitoring (PEM). Our
      objective was to investigate whether there is a clinically relevant difference in
      incidence of reported symptomatic (acid/peptic) and complicated upper GI
      conditions (perforations/bleeding) between celecoxib and meloxicam during use in
      general practice. METHODS: Patients were identified from dispensed prescriptions
      written by general practitioners (GPs) for meloxicam (December 1996 to March
      1997) and celecoxib (May to December 2000). Simple questionnaires requesting
      details of events occurring during/after treatment and potential risk factors
      (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3
      months of treatment) were posted to prescribing GPs at least 6 months after the
      first prescription for each patient. Incidence rates of the first event were
      calculated; crude and adjusted rate ratios (RR) obtained using regression
      modelling. RESULTS: For celecoxib and meloxicam, respectively, 1054 (6.0%) and
      1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events whereas 42
      (0.2%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding).
      A higher proportion of the celecoxib cohort had an indication for osteoarthritis
      (28.1 vs 23.2%), were female (68.3 vs 67.1%), were aged 60 yr or more (59.5 vs
      55.0%), were prescribed NSAIDs within 3 months of starting treatment (49.4 vs
      47.9%), and had a past medical history of upper GI conditions (54.7 vs 29.2%)
      than those prescribed meloxicam. This suggests differential channelling of groups
      at higher risk of such events on to celecoxib compared with meloxicam. There was
      no difference between the two drugs in the time to occurrence of either group of
      event. The RR over the 270-day study period for celecoxib compared with meloxicam
      were 0.77 (95% CI 0.69, 0.85) and 0.56 (95% CI 0.32, 0.96) for symptomatic
      (acid/peptic) upper GI events and complicated upper GI conditions
      (perforations/bleeding), respectively, adjusted for age, age2, sex, indication,
      medical history of upper GI problems and whether NSAIDs were prescribed within 3
      months prior to starting treatment. CONCLUSIONS: This study reports a relative
      reduction (23%) in the incidence of symptomatic (acid/peptic) GI events, and a
      relative reduction (44%) in the incidence rate of complicated upper GI conditions
      (perforations/bleeding) for celecoxib compared with meloxicam.

PMID- 12810930
TI  - Sex differences in knee cartilage volume in adults: role of body and bone size,
      age and physical activity.
AB  - OBJECTIVE: To test the hypothesis that sex differences in knee cartilage volume
      may be mediated through body and bone size, age and/or physical activity.
      METHODS: A cross-sectional convenience sample of 372 subjects (males 43%; mean
      age 45 yr, range 26-61) was studied. Articular cartilage volumes and bone size
      were determined at the patella, medial and lateral tibia by processing images
      acquired in the sagittal plane using T1-weighted fat saturation magnetic
      resonance imaging. Height, weight, physical activity (lower limb muscle strength,
      endurance fitness and questionnaire items) and radiographic osteoarthritis (ROA)
      were measured. RESULTS: Gender explained 33-42% of the variation in knee
      cartilage volumes (all P < 0.001). Males had 33-42% higher cartilage volume than
      females at all sites. In the whole group, the magnitude of sex differences
      decreased to 8-18% after adjustment for body height, weight and bone size, but
      remained significant (all P < 0.05). Further adjustment for physical activity had
      no effect on the sex differences. The sex differences in cartilage volume were
      greater in those aged over 50 compared with those aged under 50 (P < 0.05 for age
      sex interaction at all sites) and were independent of ROA. CONCLUSIONS: Men have
      substantially higher knee cartilage volumes than women. These sex differences
      appear to be mediated in part by body and bone size but a significant amount
      remains unexplained. Furthermore, the differences become more marked over the age
      of 50 yr suggesting that both cartilage development and cartilage loss in later
      life contribute to sex differences in cartilage volume. Further longitudinal
      studies in large samples will be required to confirm these findings.

PMID- 12810931
TI  - Ciprofloxacin reduces the stimulation of prostaglandin E(2) output by interleukin
      1beta in human tendon-derived cells.
AB  - OBJECTIVE: Fluoroquinolone antibiotics such as ciprofloxacin can induce tendon
      pathology and have various effects on tendon-derived cells in culture. We are
      investigating whether ciprofloxacin modifies signalling responses in tendon
      cells. METHODS: Human Achilles tendon-derived cells were preincubated with or
      without ciprofloxacin (50 mug/ml) and were then challenged with interleukin-1beta
      (IL-1beta, 1 ng/ml) for up to 48 h. Prostaglandin E2 (PGE2) output was assayed by
      ELISA. The expression of cyclooxygenase-2 (COX-2) was examined by Western
      blotting. RESULTS: IL-1beta stimulated a substantial and prolonged increase in
      the output of PGE2. Preincubation with ciprofloxacin reduced IL-1beta-induced
      PGE2 output at all times tested; the reduction at 48 h was 69% (99% confidence
      interval 59-79%; 15 experiments). Norfloxacin and ofloxacin also reduced PGE2
      output. However, ciprofloxacin did not affect the induction of COX-2 by IL-1beta,
      measured at 4 or 48 h. CONCLUSIONS: Ciprofloxacin reduces IL-1beta-induced PGE2
      output in tendon-derived cells. The reduction in PGE2 output could modulate
      various cellular activities of IL-1beta, and may be implicated in fluoroquinolone
      induced tendinopathy.

PMID- 12810932
TI  - A biopsychosocial model of pain and depression in rheumatoid arthritis: a 12
      month longitudinal study.
AB  - OBJECTIVE: To cross-validate a biopsychosocial model using physical disability,
      helplessness and passive coping to predict depression and pain in rheumatoid
      arthritis (RA). METHODS: Clinical and psychological measures were collected from
      157 RA patients at three time points over a period of 12 months. Path analysis
      was used for cross-sectional and longitudinal prediction of depression and pain.
      RESULTS: Helplessness and passive coping were found to be significant mediators
      of the relationship between the physical disability and future depression and
      pain. Cross-sectionally, the predictive model could account for 52-94% of the
      variance of pain and 37-71% of the variance of depression. Longitudinally, the
      predictive model could explain 29-43% of the variance of pain and 21-33% of the
      variance of depression. CONCLUSIONS: These results suggest that physical
      disability, helplessness and passive coping have a significant impact on the
      levels of pain and depression experienced by RA patients.

PMID- 12810933
TI  - Musculoskeletal ultrasonography in Europe: results of a rheumatologist-based
      survey at a EULAR meeting.
AB  - OBJECTIVE: To document the practice of musculoskeletal ultrasound (US) by a
      sample of European rheumatologists attending an annual general meeting of the
      European League Against Rheumatism (EULAR). METHODS: English-language
      questionnaires were distributed to 180 randomly selected participants attending
      imaging-related sessions at the XIV EULAR meeting in Glasgow, UK, in 1999. The
      questionnaire was divided into four sections: Demographics, Education and
      Training, Current Practice, and Equipment. RESULTS: Ninety-two rheumatologists
      responded, representing 74 centres from 19 European countries. Seventy-eight
      (85%) of the respondents either already used US in their clinical practice or
      would like to use it in the future. Thirty-seven (40%) respondents performed US
      within their own department. Few had received training at undergraduate level and
      most had learned informally or by attending courses. Scans were considered most
      useful for large joints and ligaments/tendons. Only 28 (30%) respondents valued
      US for guided injections. CONCLUSIONS: This study, although containing an element
      of selection bias, confirms a great interest in musculoskeletal US by
      rheumatologists across Europe and a demand which is likely to increase. The
      reported variation in training and practice between countries suggests a need for
      standardized training guidelines.

PMID- 12810934
TI  - Dimension-specific burden of caregiving among partners of rheumatoid arthritis
      patients.
AB  - OBJECTIVES: To assess subjective caregiver burden among partners of rheumatoid
      arthritis (RA) patients and to identify partner and patient variables and
      objective caregiver burden related to subjective caregiver burden. METHODS: In
      2001, 134 patients diagnosed with RA and their caregiving partners participated
      in a postal questionnaire survey. Information was gathered on age, gender and
      health problems of patient and partner, disease duration of the patient,
      objective caregiver burden and subjective caregiver burden of the partner (using
      the multidimensional Caregiver Reaction Assessment). Correlation coefficients
      were computed between the subjective caregiver burden dimensions. Multivariate
      analyses were performed to identify variables that explained the variation in
      subjective burden. RESULTS: Partners of RA patients derived, on average, a high
      level of self-esteem from giving care. Negative subjective caregiver burden was
      to a large degree caused by a disrupted schedule and to a smaller degree by a
      lack of family support, financial problems and loss of physical strength.
      Problems of the partner with mobility or with pain/discomfort and problems of the
      patient with self-care activities and activities of daily life had the largest
      impact on negative levels of subjective caregiver burden. CONCLUSIONS: Health
      parameters of the patient and partner have a considerable predictive value for
      the development of high levels of subjective burden in partners of RA patients.
      Support strategies should be developed for partners of RA patients, and should
      focus especially on reducing the burden caused by a disrupted schedule, and
      simultaneously on increasing the focus of caregivers on the positive aspects of
      caregiving.

PMID- 12810935
TI  - Current concepts and new developments in the treatment of psoriatic arthritis.
AB  - OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy
      characterized by the association of arthritis with psoriasis. Many agents have
      been proposed for the treatment of PsA, but their use is based more on clinical
      experience than on sound scientific evidence. METHODS: We reviewed MedLine up to
      November 2002, searching for 'psoriatic arthritis', 'drug therapy, 'controlled
      trials' and 'outcomes' and all possible acronyms for these terms. All relevant
      papers were then examined in detail. RESULTS: PsA is a condition that runs a
      variable clinical course. Mild forms can usually be controlled by non-steroidal
      anti-inflammatory drugs (NSAIDs). Intra-articular glucocorticoid injections are
      indicated in patients with persistent mono- or oligoarthritis. Patients with
      severe and progressive articular disease not responsive to NSAIDs should be
      treated with disease-modifying anti-rheumatic drugs (DMARDs) to prevent joint
      damage and disability. Currently, methotrexate and sulphasalazine are considered
      the DMARDs of choice, but the evidence for the use of methotrexate in PsA is
      still largely empirical, while the clinical benefit induced by sulphasalazine
      appears to be modest. Other DMARDs proposed for the treatment of PsA include
      cyclosporin, gold salts and, more recently, leflunomide. However, none of the
      DMARDs available to date are effective in the treatment of psoriatic
      pelvispondylitis; in addition, a number of patients with severe peripheral
      arthritis fail to respond to standard DMARDs. Recently, tumour necrosis factor
      alpha inhibitors have proved effective in many PsA patients with pelvispondylitis
      or recalcitrant peripheral synovitis. CONCLUSIONS: None of the current treatments
      for PsA is curative, but significant clinical amelioration can be achieved in the
      vast majority of patients. Identification and prompt treatment of patients with
      severe articular disease is crucial for the achievement of a satisfactory
      clinical response and the improvement of the long-term outcome.

PMID- 12810936
TI  - Prognostic factors in lateral epicondylitis: a randomized trial with one-year
      follow-up in 266 new cases treated with minimal occupational intervention or the
      usual approach in general practice.
AB  - OBJECTIVES: To determine whether minimal intervention by occupational specialists
      involving information about the disorder, encouragement to stay active and
      instruction in graded self-performed exercises could enhance the prognosis of
      lateral epicondylitis compared with the treatment usually given in general
      practice, to quantify workplace factors associated with the prognosis, and to
      consider treatments given in general practice. METHODS: A randomized controlled
      trial was performed in a cohort of 266 consecutive new cases of lateral
      epicondylitis diagnosed in general practice. Workplace factors were assessed with
      questionnaires at the time of inclusion, and patients completed follow-ups at 3,
      6 and 12 months. Status at 1 yr was assessed as overall improvement and pain
      reduction compared with the time of diagnosis. General practitioners (GPs)
      registered the treatments given for both cases and controls during follow-up.
      Numbers of contacts with GPs and physiotherapists were obtained from the National
      Health Insurance registry. Prognostic factors were analysed by multiple logistic
      regression analysis. RESULTS: After 1 yr, 83% of cases showed improvement in the
      condition, but the intervention was found to have had no advantage. Poor overall
      improvement was associated with employment in manual jobs [odds ratio (OR) 3.0,
      95% confidence interval (CI) 1.0-8.7], a high level of physical strain at work
      (OR 8.5, CI 1.0-74.7) and a high level of pain at baseline (OR 2.3, CI 1.0-5.3).
      Pain reduction less than 50% was associated with manual jobs (OR 2.3, CI 1.1
      5.1), high physical strain at work (OR 3.6, CI 1.0-12.9), high baseline distress
      (OR 1.9, CI 1.0-4.0) and tennis elbow on the dominant side (OR 3.1, CI 1.4-6.8).
      The intervention group received less treatment and fewer treatment modalities,
      but the intervention was not followed by a reduction in the number of visits to
      GPs and physiotherapist clinics during 12 months of follow-up. CONCLUSIONS: Poor
      prognosis at 1 yr of follow-up for lateral epicondylitis was related to manual
      work and high baseline pain, whilst no relation was found between the type of
      medical treatment given/chosen and prognosis. This may have implications for the
      future management of lateral epicondylitis in terms of a greater focus on
      interaction with the workplace regarding job modification to reduce physical
      demands during recovery.

PMID- 12810938
TI  - Comparison of intra-articular triamcinolone hexacetonide and triamcinolone
      acetonide in oligoarticular juvenile idiopathic arthritis.
AB  - OBJECTIVE: To compare the efficacy and safety of intra-articular triamcinolone
      hexacetonide (TH) and triamcinolone acetonide (TA) in children with
      oligoarticular juvenile idiopathic arthritis (JIA). METHODS: One hundred and
      thirty joints of 85 patients undergoing intra-articular injections were randomly
      treated with either TH or TA depending on the availability of the drug. The
      efficacy of both treatments was evaluated prospectively in a blinded fashion. A
      good response was defined as a decrease in the articular score of > or =60% from
      baseline. Clinical, laboratory and immunological variables were noted in order to
      examine possible factors, other than treatment, predictive of the result.
      RESULTS: Seventy injections were performed using TH and 60 with TA. The two
      groups were comparable for clinical, immunological and laboratory
      characteristics. The rate of response was significantly higher with TH than with
      TA: 81.4% vs 53.3% (P = 0.001) at 6 months, 67.1 vs 43.3% (P = 0.006) at 12
      months, and 60 vs 33.3% (P = 0.002) at 24 months. CONCLUSION: At comparable doses
      TH appeared to be much more effective than TA for intra-articular use, in both
      short- and long-term follow-up. This result was not affected by disease duration
      or degree of local and systemic inflammation.

PMID- 12810937
TI  - Valdecoxib is as effective as diclofenac in the management of rheumatoid
      arthritis with a lower incidence of gastroduodenal ulcers: results of a 26-week
      trial.
AB  - OBJECTIVE: To compare the efficacy and upper gastrointestinal (GI) safety of
      valdecoxib 20 and 40 mg daily with those of diclofenac 75 mg slow release (SR)
      twice daily in treating rheumatoid arthritis (RA). METHODS: Seven hundred and
      twenty-two patients with adult-onset RA were enrolled into this 26-week,
      randomized, multicentre, double-blind, parallel-group study (246 in the
      valdecoxib 20 mg daily arm, 237 in the valdecoxib 40 mg daily arm and 239 in the
      diclofenac 75 mg SR daily arm). Acetylsalicylic acid use (< or =325 mg per day)
      was similar across all groups: 5.4% in the diclofenac group, 5.7% in the
      valdecoxib 20 mg group and 5.9% in the valdecoxib 40 mg group. Efficacy was
      measured by the Patient's Assessment of Arthritis Pain [visual analogue scale
      (VAS)] and the modified Health Assessment Questionnaire (mHAQ) at baseline and at
      weeks 2, 6, 8, 12, 18 and 26 of treatment, or at early termination. Upper GI
      safety was evaluated by endoscopy at the end of treatment, which took place no
      more than 2 days after the last dose of study medication or at early termination.
      RESULTS: Valdecoxib 20 and 40 mg daily were comparable to diclofenac 75 mg SR
      twice daily in treating the signs and symptoms of RA. No significant differences
      were observed between treatment groups with respect to mean changes from baseline
      in the Patient's Assessment of Arthritis Pain (VAS) or mHAQ. The incidence of
      gastroduodenal ulcers in patients receiving valdecoxib 20 mg daily (6%) and
      valdecoxib 40 mg daily (4%) was significantly lower (P < 0.001) than in patients
      receiving diclofenac 75 mg SR twice daily (16%). Valdecoxib 20 mg daily was also
      associated with significantly improved GI tolerability (P = 0.035) compared with
      diclofenac. CONCLUSIONS: Single daily doses of valdecoxib 20 and 40 mg provided
      efficacy comparable to that of diclofenac, with a superior upper GI safety
      profile in the long-term treatment of RA patients.

PMID- 12810939
TI  - Bone health in patients with fibromyalgia.
AB  - OBJECTIVES: To determine whether women with fibromyalgia are at increased risk of
      developing osteoporosis or osteomalacia. METHODS: Forty premenopausal women with
      fibromyalgia and 37 age-matched female controls were studied. Broadband
      ultrasound attenuation (BUA) and velocity of sound (VOS) were measured at the
      calcaneum and bone mineral density was measured at the forearm and lumbar spine
      using dual-energy X-ray absorptiometry. Serum calcium, alkaline phosphatase,
      gamma-glutamyl transferase, 25-hydroxyvitamin D and plasma viscosity were
      measured in all subjects and parathyroid hormone was measured in subjects
      recruited in the latter part of the study. RESULTS: Seventeen patients with
      fibromyalgia syndrome and seven controls had 25-hydroxyvitamin D concentrations
      <20 nmol/l (P < 0.015) and in three FMS patients serum parathyroid hormone was
      raised. Bone density in fibromyalgia patients was slightly lower at the mid
      distal forearm but comparable to that in controls at other sites. CONCLUSIONS:
      There is no reason to recommend routine bone densitometry in fibromyalgia
      patients. However, vitamin D subnutrition is common in these patients and this
      should be sought.

PMID- 12810940
TI  - Ethnic differences in responses to disease modifying drugs.
AB  - BACKGROUND AND OBJECTIVE: The UK has a growing South Asian population. In the
      South Asian population of Bradford people appear to be less tolerant of disease
      modifying anti-rheumatic drugs (DMARDs). One reason for this may be poor
      communication during patient education, which is generally designed for white
      North European people. Our objective was to obtain information on DMARDs that
      were used, the duration of their use and reasons for their discontinuation
      between ethnic groups. METHODS: Retrospective data were obtained from the
      inception of a clinical database in August 1993 to July 2001 using 'DMARD' as the
      main search item; a total of 5479 DMARD prescriptions were represented in the
      data. A subset of the data so obtained was cross-checked against the patient
      records. Inaccuracies in start and stop dates prior to January 1997, together
      with other reasons (such as incomplete data), resulted in a final data set of
      2356 drugs. The drugs had been given to 1391 patients. Overwhelmingly, the two
      main ethnic groups were North European (1191 patients) and South Asian (193
      patients). RESULTS: The final data set was based on the following drugs:
      azathioprine (179); antimalarials (chloroquine and hydroxychloroquine) (407);
      corticosteroids (648); D-penicillamine (61); methotrexate (459); sulphasalazine
      (493); and sodium aurothiomalate (96). Survival analysis showed that age and drug
      type were important variables influencing the duration of time spent on a drug
      before discontinuation. For age, drug survival was better for the older age group
      [log rank test, chi2(3) = 29.1, P < 0.0001]. For drug, survival was best for
      steroids, followed in decreasing order by sulphasalazine, methotrexate, sodium
      aurothiomalate, azathioprine, antimalarials and D-penicillamine [chi2(6) = 99.3,
      P < 0.00001). For all drugs, the main ethnic groups differed, with a 12-month
      survival rate of drugs in the North European group of 0.742 (95% confidence
      interval 0.693-0.791) and the South Asian group of 0.665 (95% confidence interval
      0.645-0.684) [log rank test, chi2(1) = 18.19, P < 0.00001]. As the two main
      ethnic groups differed with respect to age and drug type, further survival
      analysis adjusting for these variables confirmed a significant difference between
      the two ethnic groups. The main reasons for terminating the DMARD differed
      between the groups: people of South Asian origin were more likely to discontinue
      the drug because of rashes, lack of efficacy and worry about the potential side
      effects of the drug. CONCLUSIONS: People of South Asian ethnic status terminate
      DMARD therapy sooner than North Europeans. The reasons for this difference are
      not clear but may concern problems with effective communication, cultural
      differences in attitudes to chronic illness or genetic polymorphisms in drug
      metabolism.

PMID- 12810941
TI  - Horizontal gene transfer in eukaryotic algal evolution.

PMID- 12810942
TI  - Retuning the misfiring brain.

PMID- 12810943
TI  - What happens if the room at the bottom runs out? A close look at small water
      pores.

PMID- 12810944
TI  - Replication of the herpes simplex virus genome: does it really go around in
      circles?

PMID- 12810945
TI  - Epigenetic inactivation of CHFR in human tumors.
AB  - Cell-cycle checkpoints controlling the orderly progression through mitosis are
      frequently disrupted in human cancers. One such checkpoint, entry into metaphase,
      is regulated by the CHFR gene encoding a protein possessing forkhead-associated
      and RING finger domains as well as ubiquitin-ligase activity. Although defects in
      this checkpoint have been described, the molecular basis and prevalence of CHFR
      inactivation in human tumors are still not fully understood. To address this
      question, we analyzed the pattern of CHFR expression in a number of human cancer
      cell lines and primary tumors. We found CpG methylation-dependent silencing of
      CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers,
      53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression
      of CHFR was precisely correlated with both CpG methylation and deacetylation of
      histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation
      and thus silencing of CHFR depended on the activities of two DNA
      methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR
      expression. Finally, cells with CHFR methylation had an intrinsically high
      mitotic index when treated with microtubule inhibitor. This means that cells in
      which CHFR was epigenetically inactivated constitute loss-of-function alleles for
      mitotic checkpoint control. Taken together, these findings shed light on a
      pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that
      inactivation of checkpoint genes is much more widespread than previously
      suspected.

PMID- 12810947
TI  - Bacterial cell division spirals into control.

PMID- 12810946
TI  - Mechanotransduction and flow across the endothelial glycocalyx.
AB  - In this inaugural paper, we shall provide an overview of the endothelial surface
      layer or glycocalyx in several roles: as a transport barrier, as a porous
      hydrodynamic interface in the motion of red and white cells in microvessels, and
      as a mechanotransducer of fluid shearing stresses to the actin cortical
      cytoskeleton of the endothelial cell. These functions will be examined from a new
      perspective, the quasiperiodic ultrastructural model proposed in Squire et al.
      [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. & Michel, C. (2001) J.
      Struct. Biol. 136, 239-255] for the 3D organization of the endothelial surface
      layer and its linkage to the submembranous scaffold. We shall show that the core
      proteins in the bush-like structures comprising the matrix have a flexural
      rigidity, EI, that is sufficiently stiff to serve as a molecular filter for
      plasma proteins and as an exquisitely designed transducer of fluid shearing
      stresses. However, EI is inadequate to prevent the buckling of these protein
      structures during the intermittent motion of red cells or the penetration of
      white cell microvilli. In these cellular interactions, the viscous draining
      resistance of the matrix is essential for preventing adhesive molecular
      interactions between proteins in the endothelial membrane and circulating
      cellular components.

PMID- 12810948
TI  - Determination of the membrane topology of Ost4p and its subunit interactions in
      the oligosaccharyltransferase complex in Saccharomyces cerevisiae.
AB  - Ost4p is a minimembrane protein containing only 36 amino acids and is a subunit
      of oligosaccharyltransferase (OT) in Saccharomyces cerevisiae. It was found
      previously when amino acid residues 18-25 of Ost4p were mutated to ionizable
      amino acids and defects were observed in the interaction between Ost4p and either
      Stt3p or Ost3p, two other components of OT. The transmembrane segment of Ost4p is
      likely to extend from residues 10-25. This is consistent with the finding that
      alpha-helicity is estimated to be 36% by CD analysis of synthetic Ost4p in
      liposomes. This value is in reasonable agreement with the assumption that amino
      acids 10-25 (16 of 36 or 44%) are transmembrane. Therefore, the mutation
      sensitive region (residues 18-25) is localized to only one half of the putative
      transmembrane domain of Ost4p. To learn where this region of Ost4p is situated in
      relation to the faces of endoplasmic reticulum (ER) membrane, we determined the
      membrane topology of Ost4p using an in vivo method and established that it is an
      Nlumen-Ccyto, type I membrane protein. These results indicate that the mutation
      sensitive region of Ost4p is localized in the cytoplasmic leaflet of the ER
      membrane. In the current study, we also observed a loss of direct interaction
      between Ost3p and Stt3p in the presence of ost4 temperature-sensitive mutants,
      which indicates Ost4p, via interactions with amino acid residues in the cytosolic
      leaflet of the ER membrane, functions to bind these two proteins together in a
      subcomplex of OT.

PMID- 12810949
TI  - Brain repair by cell replacement and regeneration.

PMID- 12810950
TI  - Human acetyl-CoA carboxylase 1 gene: presence of three promoters and
      heterogeneity at the 5'-untranslated mRNA region.
AB  - Acetyl-CoA carboxylase 1 (ACC1) catalyzes the formation of malonyl-CoA, the C2
      donor for de novo synthesis of long-chain fatty acids. We have identified 64
      exons, including 7 alternatively spliced minor exons (1A, 1B, 1C, 3, 5A', 5A, and
      5B) in human ACC1 gene ( approximately 330 kb). The gene is regulated by three
      promoters (PI, PII, and PIII), which are located upstream of exons 1, 2, and 5A,
      respectively. PI is a constitutive promoter and has no homology with the PI
      sequences of other mammalian ACC1. PII is regulated by various hormones. PIII is
      expressed in a tissue-specific manner. The presence of several alternatively
      spliced exons does not alter the translation of the 265-kDa ACC1 protein starting
      from an ATG present in exon 5. Translation of PIII transcripts from exon 5A
      generates a 259-kDa isoform in which the N-terminal 75 aa of 265-kDa ACC1 are
      replaced with a new sequence of 17 aa. Interestingly, the inclusion of exon 5B
      between 5A and 6 in PIII transcripts would yield a third 257-kDa isoform, which
      is translated from an ATG in exon 6. However, the presence of exon 5B in PI and
      PII transcripts leads to an in-frame stop codon that results in an ACC1-related
      77-aa peptide. The presence of alternatively spliced exons and three isoforms of
      ACC1 could contribute to overall ACC1 activity either by influencing the mRNA
      stability and translational efficiency or by increasing the stability and
      specific activity of the ACC1 protein, respectively.

PMID- 12810951
TI  - Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice
      cultures of postnatal rat and mouse cerebellum.
AB  - Mifepristone (RU486), which binds with high affinity to both progesterone and
      glucocorticosteroid receptors (PR and GR), is well known for its use in the
      termination of unwanted pregnancy, but other activities including neuroprotection
      have been suggested. Cerebellar organotypic cultures from 3 to 7 postnatal day
      rat (P3-P7) were studied to examine the neuroprotective potential of RU486. In
      such cultures, Purkinje cells enter a process of apoptosis with a maximum at P3.
      This study shows that RU486 (20 microM) can protect Purkinje cells from this
      apoptotic process. The neuroprotective effect did involve neither PR nor GR,
      because it could not be mimicked or inhibited by other ligands of these
      receptors, and because it still took place in PR mutant (PR-KO) mice and in brain
      specific GR mutant mice (GRNes/Cre). Potent antioxidant agents did not prevent
      Purkinje cells from this developmental cell death. The neuroprotective effect of
      RU486 could also be observed in pathological Purkinje cell death. Indeed, this
      steroid is able to prevent Purkinje cells from death in organotypic cultures of
      cerebellar slices from Purkinje cell degeneration (pcd) mutant mice, a murine
      model of hereditary neurodegenerative ataxia. In P0 cerebellar slices treated
      with RU486 for 6 days and further kept in culture up to 21 days, the synthetic
      steroid increased by 16.2-fold the survival of pcd/pcd Purkinje cells. Our
      results show that RU486 may act through a new mechanism, not yet elucidated, to
      protect Purkinje cells from death.

PMID- 12810952
TI  - Pronounced reduction in adenoma recurrence associated with aspirin use and a
      polymorphism in the ornithine decarboxylase gene.
AB  - Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli
      gene (APC) and show defects in APC-dependent signaling. APC influences the
      expression of several genes, including the c-myc oncogene and its antagonist
      Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is
      a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis.
      A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which
      lies between two myc-binding domains. This region is known to affect ODC
      transcription, but no data exist on the relationship of this polymorphism to risk
      of colorectal neoplasia in humans. We show that individuals homozygous for the
      minor ODC A-allele who reported using aspirin are approximately 0.10 times as
      likely to have an adenoma recurrence as non-aspirin users homozygous for the
      major G-allele. Mad1 selectively suppressed the activity of the ODC promoter
      containing the A-allele, but not the G-allele, in a human colon cancer-derived
      cell line (HT29). Aspirin (>or=10 microM) did not affect ODC allele-specific
      promoter activity but did activate polyamine catabolism and lower polyamine
      content in HT29 cells. We propose that the ODC polymorphism and aspirin act
      independently to reduce the risk of adenoma recurrence by suppressing synthesis
      and activating catabolism, respectively, of colonic mucosal polyamines. These
      findings confirm the hypothesis that the ODC polymorphism is a genetic marker for
      colon cancer risk, and support the use of ODC inhibitors and aspirin, or other
      nonsteroidal antiinflammatory drugs (NSAIDs), in combination as a strategy for
      colon cancer prevention.

PMID- 12810953
TI  - Deletion of histidine triad nucleotide-binding protein 1/PKC-interacting protein
      in mice enhances cell growth and carcinogenesis.
AB  - PKC-interacting protein (PKCI), also designated histidine triad nucleotide
      binding protein 1, belongs to the histidine triad (HIT) family of proteins. Its
      structure is highly conserved from bacteria to humans and shares homology with
      the tumor-suppressor gene fragile histidine triad (FHIT). Although it was
      originally thought to inhibit PKC, its actual physiologic function is not known.
      Therefore, we used the technique of homologous recombination to generate
      homozygous deleted PKCI-/- mice. These mice display normal fetal and adult
      development. However, when mouse embryo fibroblasts were established from 13.5
      day embryos and serially passaged the PKCI-/- cells displayed an increase in
      growth rate and underwent spontaneous immortalization, whereas the PKCI+/+ cells
      senesced and ceased growing. Furthermore, the PKCI-/- mouse embryo fibroblasts
      displayed increased resistance to cytotoxicity by ionizing radiation. In view of
      these findings we examined possible effects of PKCI on susceptibility to
      carcinogenicity. Both PKCI+/+ and PKCI-/- mice were treated with the chemical
      carcinogen N-nitrosomethylbenzylamine (NMBA) by intragastric administration and
      killed 12 weeks later. As expected with this protocol, NMBA induced squamous
      tumors (both papillomas and carcinomas) of the forestomach. The incidence,
      multiplicity per mouse, volume, and degree of malignancy of these tumors were
      significantly greater in the PKCI-/- than in the PKCI+/+ mice. Furthermore, four
      adenomas and one adenocarcinoma of the glandular stomach were found in the NMBA
      treated PKCI-/- mice but no tumors of the glandular stomach were found in the
      NMBA-treated PKCI+/+ mice or in any of the untreated mice. Taken together, these
      findings suggest that, like FHIT, PKCI may normally play a tumor-suppressor role.
      The possible role of PKCI as a tumor suppressor in humans remains to be
      determined.

PMID- 12810954
TI  - The complete genome sequence of the carcinogenic bacterium Helicobacter
      hepaticus.
AB  - Helicobacter hepaticus causes chronic hepatitis and liver cancer in mice. It is
      the prototype enterohepatic Helicobacter species and a close relative of
      Helicobacter pylori, also a recognized carcinogen. Here we report the complete
      genome sequence of H. hepaticus ATCC51449. H. hepaticus has a circular chromosome
      of 1,799,146 base pairs, predicted to encode 1,875 proteins. A total of 938, 953,
      and 821 proteins have orthologs in H. pylori, Campylobacter jejuni, and both
      pathogens, respectively. H. hepaticus lacks orthologs of most known H. pylori
      virulence factors, including adhesins, the VacA cytotoxin, and almost all cag
      pathogenicity island proteins, but has orthologs of the C. jejuni adhesin PEB1
      and the cytolethal distending toxin (CDT). The genome contains a 71-kb genomic
      island (HHGI1) and several genomic islets whose G+C content differs from the rest
      of the genome. HHGI1 encodes three basic components of a type IV secretion system
      and other virulence protein homologs, suggesting a role of HHGI1 in
      pathogenicity. The genomic variability of H. hepaticus was assessed by comparing
      the genomes of 12 H. hepaticus strains with the sequenced genome by microarray
      hybridization. Although five strains, including all those known to have caused
      liver disease, were indistinguishable from ATCC51449, other strains lacked
      between 85 and 229 genes, including large parts of HHGI1, demonstrating extensive
      variation of genome content within the species.

PMID- 12810955
TI  - Caspase 8 small interfering RNA prevents acute liver failure in mice.
AB  - A major concern in therapy of acute liver failure is protection of hepatocytes to
      prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a
      powerful tool to silence gene expression in mammalian cells. To evaluate the
      therapeutic efficacy of siRNA in vivo we used different mouse models of acute
      liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme
      in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA
      results in inhibition of caspase 8 gene expression in the liver, thereby
      preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8
      siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95)
      antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a
      clinical situation the siRNAs most likely would be applied after the onset of
      acute liver failure. Therefore we injected caspase 8 siRNA at a time point during
      AdFasL- and adenovirus wild type (Adwt)-mediated liver failure with already
      elevated liver transaminases. Improvement of survival due to RNA interference was
      significant even when caspase 8 siRNA was applied during ongoing acute liver
      failure. In addition, it is of particular interest that caspase 8 siRNA treatment
      was successful not only in acute liver failure mediated by specific Fas agonistic
      agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which
      is an animal model reflecting multiple molecular mechanisms involved in human
      acute viral hepatitis. Consequently, our data raise hope for future successful
      application of siRNA in patients with acute liver failure.

PMID- 12810956
TI  - An unusual type IB topoisomerase from African trypanosomes.
AB  - African trypanosomes are ancient eukaryotes that cause lethal disease in humans
      and cattle. Available drugs are inadequate and the need for new therapeutic
      targets is great. Trypanosoma brucei and related pathogens differ strikingly from
      higher eukaryotes in many aspects of nucleic acid structure and metabolism. We
      find yet another example of this in their unusual DNA topoisomerase IB. Type IB
      topoisomerases relieve the supercoils that accumulate during DNA and RNA
      synthesis, and are of considerable importance as the target for antitumor
      camptothecins. Dozens of type IB topoisomerases sequenced from eukaryotes,
      bacteria, and pox viruses are all encoded by a single gene that predictably
      contains a highly conserved DNA binding domain and C-terminal catalytic domain,
      linked by a nonconserved hydrophilic region. We find that topoisomerase IB in T.
      brucei is encoded by two genes: one for the DNA-binding domain and a second for
      the C-terminal catalytic domain. In keeping with this, highly purified fractions
      of native T. brucei topoisomerase IB catalytic activity contain two proteins, of
      90 and 36 kDa. The native enzyme is conventional in its Mg2+-independence,
      ability to relax positive and negative supercoils, and inhibition by
      camptothecin. Camptothecin promotes the formation of a covalent complex between
      32P-labeled substrate DNA and the small subunit. This unusual structural
      organization may provide a missing link in the evolution of type IB enzymes,
      which are thought to have arisen over time from the fusion of two independent
      domains. It also provides another basis for the design of selectively toxic drug
      candidates.

PMID- 12810957
TI  - Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian
      evolution.
AB  - The human and mouse genomic sequences provide evidence for a larger number of
      rearrangements than previously thought and reveal extensive reuse of breakpoints
      from the same short fragile regions. Breakpoint clustering in regions implicated
      in cancer and infertility have been reported in previous studies; we report here
      on breakpoint clustering in chromosome evolution. This clustering reveals
      limitations of the widely accepted random breakage theory that has remained
      unchallenged since the mid-1980s. The genome rearrangement analysis of the human
      and mouse genomes implies the existence of a large number of very short "hidden"
      synteny blocks that were invisible in the comparative mapping data and ignored in
      the random breakage model. These blocks are defined by closely located
      breakpoints and are often hard to detect. Our results suggest a model of
      chromosome evolution that postulates that mammalian genomes are mosaics of
      fragile regions with high propensity for rearrangements and solid regions with
      low propensity for rearrangements.

PMID- 12810958
TI  - Differential proteasomal processing of hydrophobic and hydrophilic protein
      regions: contribution to cytotoxic T lymphocyte epitope clustering in HIV-1-Nef.
AB  - HIV proteins contain a multitude of naturally processed cytotoxic T lymphocyte
      (CTL) epitopes that concentrate in clusters. The molecular basis of epitope
      clustering is of interest for understanding HIV immunogenicity and for vaccine
      design. We show that the CTL epitope clusters of HIV proteins predominantly
      coincide with hydrophobic regions, whereas the noncluster regions are
      predominantly hydrophilic. Analysis of the proteasomal degradation products of
      full-length HIV-Nef revealed a differential sensitivity of cluster and noncluster
      regions to proteasomal processing. Compared with the epitope-scarce noncluster
      regions, cluster regions are digested by proteasomes more intensively and with
      greater preference for hydrophobic P1 residues, resulting in substantially
      greater numbers of fragments with the sizes and COOH termini typical of epitopes
      and their precursors. Indeed, many of these fragments correspond to endogenously
      processed Nef epitopes and/or their potential precursors. The results suggest
      that differential proteasomal processing contributes importantly to the
      clustering of CTL epitopes in hydrophobic regions.

PMID- 12810960
TI  - Additive effects of simulated climate changes, elevated CO2, and nitrogen
      deposition on grassland diversity.
AB  - Biodiversity responses to ongoing climate and atmospheric changes will affect
      both ecosystem processes and the delivery of ecosystem goods and services.
      Combined effects of co-occurring global changes on diversity, however, are poorly
      understood. We examined plant diversity responses in a California annual
      grassland to manipulations of four global environmental changes, singly and in
      combination: elevated CO2, warming, precipitation, and nitrogen deposition. After
      3 years, elevated CO2 and nitrogen deposition each reduced plant diversity,
      whereas elevated precipitation increased it and warming had no significant
      effect. Diversity responses to both single and combined global change treatments
      were driven overwhelmingly by gains and losses of forb species, which make up
      most of the native plant diversity in California grasslands. Diversity responses
      across treatments also showed no consistent relationship to net primary
      production responses, illustrating that the diversity effects of these
      environmental changes could not be explained simply by changes in productivity.
      In two- to four-way combinations, simulated global changes did not interact in
      any of their effects on diversity. Our results show that climate and atmospheric
      changes can rapidly alter biological diversity, with combined effects that, at
      least in some settings, are simple, additive combinations of single-factor
      effects.

PMID- 12810959
TI  - Alginate is not a significant component of the extracellular polysaccharide
      matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms.
AB  - The bacterium Pseudomonas aeruginosa causes chronic respiratory infections in
      cystic fibrosis (CF) patients. Such infections are extremely difficult to control
      because the bacteria exhibit a biofilm-mode of growth, rendering P. aeruginosa
      resistant to antibiotics and phagocytic cells. During the course of infection, P.
      aeruginosa usually undergoes a phenotypic switch to a mucoid colony, which is
      characterized by the overproduction of the exopolysaccharide alginate. Alginate
      overproduction has been implicated in protecting P. aeruginosa from the harsh
      environment present in the CF lung, as well as facilitating its persistence as a
      biofilm by providing an extracellular matrix that promotes adherence. Because of
      its association with biofilms in CF patients, it has been assumed that alginate
      is also the primary exopolysaccharide expressed in biofilms of environmental
      nonmucoid P. aeruginosa. In this study, we examined the chemical nature of the
      biofilm matrix produced by wild-type and isogenic alginate biosynthetic mutants
      of P. aeruginosa. The results clearly indicate that alginate biosynthetic genes
      are not expressed and that alginate is not required during the formation of
      nonmucoid biofilms in two P. aeruginosa strains, PAO1 and PA14, that have
      traditionally been used to study biofilms. Because nonmucoid P. aeruginosa
      strains are the predominant environmental phenotype and are also involved in the
      initial colonization in CF patients, these studies have implications in
      understanding the early events of the infectious process in the CF airway.

PMID- 12810962
TI  - The SARS war: back to basics.

PMID- 12810963
TI  - SARS: facts and considerations for the orthopaedic community.

PMID- 12810961
TI  - Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between
      macrophages and apoptotic cells.
AB  - Tissue transglutaminase (TGase2) is a protein-crosslinking enzyme known to be
      associated with the in vivo apoptosis program. Here we report that apoptosis
      could be induced in TGase2-/- mice; however, the clearance of apoptotic cells was
      defective during the involution of thymus elicited by dexamethasone, anti-CD3
      antibody, or gamma-irradiation, and in the liver after induced hyperplasia. The
      lack of TGase2 prevented the production of active transforming growth factor
      beta1 in macrophages exposed to apoptotic cells, which is required for the up
      regulation of TGase2 in the thymus in vivo, for accelerating deletion of CD4+CD8+
      cells and for efficient phagocytosis of apoptotic bodies. The deficiency is
      associated with the development of splenomegaly, autoantibodies, and immune
      complex glomerulonephritis in TGase2-/- mice. These findings have broad
      implications not only for diseases linked to inflammation and autoimmunity but
      also for understanding the interrelationship between the apoptosis and
      phagocytosis process.

PMID- 12810964
TI  - Comparison of bone mineral density among residents of a mountain village and a
      fishing village in Japan.
AB  - OBJECTIVE: To compare the bone mineral density of residents of a mountain village
      with that of residents of a fishing village in Mie Prefecture, Japan. METHODS:
      Microdensitometry was used to measure bone mineral density of the second
      metacarpal bone of 202 participants living in a mountain village and of 852
      participants living in a fishing village to identify contributory factors for
      osteoporosis. The participants were interviewed using a questionnaire on alcohol
      consumption, fish intake, milk intake, and daily activity. RESULTS: Analysis of
      covariance revealed that bone mineral density was significantly higher among the
      participants living in a fishing village than among those living in a mountain
      village (2.5-2.9 versus 2.1-2.7 mmAl; p<0.001). A higher proportion of women in
      the fishing village than of those in the mountain village consumed alcohol (17%
      versus 10%; p<0.05). CONCLUSION: Nutrition may be a contributory factor to the
      lower incidence of osteoporosis among residents of the fishing village compared
      with those of the mountain village.

PMID- 12810965
TI  - Autologous chondrocyte implantation using a bilayer collagen membrane: a
      preliminary report.
AB  - OBJECTIVE: To present preliminary clinical experience with Matrix-induced
      autologous chondrocyte implantation, a new tissue-engineering technique for
      treatment of deep cartilage defects, in which autologous chondrocytes are seeded
      on a tridimensional scaffold provided by a bilayer type I-III collagen membrane.
      METHODS: From December 1999 to January 2001, 13 patients underwent implantation
      procedure for deep cartilage defects. Age of patients ranged from 18 to 49 years
      (mean age, 35 years). The mean defect size was 3.5 cm(2) (range, 2.0-4.5 cm(2)).
      Clinical and functional evaluation were performed using various score systems for
      the ankle and the knee, and magnetic resonance imaging was performed at 6 and 12
      months postoperatively. Membrane structure and cellular population were
      investigated by light microscopy, scanning electron microscopy, and
      electrophoresis before implantation. RESULTS: The mean follow-up was 6.5 months
      (range, 2-15 months). No complications were observed in the postoperative period.
      The 6 patients with a minimum follow-up of 6 months showed an improvement in
      clinical and functional status after surgery. Magnetic resonance images showed
      the presence of hyaline-like cartilage at the site of implantation; there was
      evidence of chondroblasts and type II collagen inside the seeded membrane.
      CONCLUSION: Matrix-induced autologous chondrocyte implantation offers several
      advantages with respect to the traditional cultured cell procedure. These include
      technical simplicity, short operating time, minimal invasiveness, and easier
      access to difficult sites. It appears to be a reliable method for the repair of
      deep cartilage defects.

PMID- 12810966
TI  - Reaming bone grafting to treat tibial shaft aseptic nonunion after plating.
AB  - OBJECTIVE: To investigate the effects of using intramedullary reaming to provide
      cancellous bone graft, and reamed intramedullary nail stabilisation to provide
      fragment stability on treating tibial shaft aseptic nonunions after plating.
      METHODS: 31 consecutive patients with tibial shaft aseptic nonunions after
      plating were prospectively treated. Indications for this technique included a
      tibial shaft nonunion with an inserted plate, a fracture level fit for
      traditional or locked nail stabilisation, absence of suspected infection and
      segmental bony defect at the time, and shortening of less than 2 cm. The plate
      was removed and the marrow cavity was reamed as widely as possible. A stable
      unlocked or locked intramedullary nail was then inserted. No extra cancellous
      bone graft was supplemented. RESULTS: 28 patients were followed up for a median
      period of 2.2 years (range, 1.0-5.2 years). All patients achieved solid union.
      The median union period was 4.5 months (range, 3.0-7.5 months). There were no
      significant complications. CONCLUSION: When reamed intramedullary nails are used
      to treat tibial shaft aseptic nonunions after plating, supplemented cancellous
      bone grafting can be spared. Despite the technique being simplified, the success
      rate is high. We therefore recommend its wide use to treat all suitable cases.

PMID- 12810967
TI  - An age- and sex-controlled matched pair analysis of T scores in ethnic Indians
      with hip fractures.
AB  - OBJECTIVE: The first study to predict peritrochanteric fractures by the use of T
      scores amongst the Indian population was performed. This study aimed to assess
      the risk of fracture around the hip in peri-menopausal and postmenopausal women,
      and in men over the age of 35 years using dual energy X-ray absorptiometry, and
      to analyse whether the result, i.e. the T score, can predict an impending hip
      fracture. METHODS: T scores of the unaffected hip in 30 patients with
      peritrochanteric fractures were determined, and matched pair analysis was done
      using a control group without fracture. All patients were from a single centre
      and were evaluated using the same scanner. RESULTS: The mean T score of the 30
      patients in the fracture group was -3.34 (range, -1.2 to -5.1; standard deviation
      [SD], 1.032), compared with the mean T score of the 30 control subjects which was
      -2.41 (range, 0.6 to -5.0; SD, 1.378). T scores of patients from the fracture
      group were significantly lower than those in the control group. CONCLUSION: We
      infer that T scores are the best predictors for fracture risk. A score of -2.5 or
      lower effectively defines patients at risk and is useful for predicting fracture
      risk in the Indian population. In patients with osteoporosis, whether a fall
      precedes the fracture or the fracture precedes a fall may not be an issue of
      debate, but can serve as a basis for prevention of additional fractures by
      instituting appropriate measures in patients at risk.

PMID- 12810968
TI  - Surgical management of malignant soft tissue tumours in patients aged 65 years or
      older.
AB  - OBJECTIVE: With the aim to determine the most effective treatment for primary
      malignant musculoskeletal tumours in patients aged 65 years or older, we reviewed
      cases of low- and high-grade neoplasms, surgical margins, surgical methods, and
      the prognoses of elderly and aged patients at our institution. METHODS: Records
      of 25 patients aged 65 years or older who had malignant soft tissue tumours from
      December 1986 to February 1997 were reviewed. Low- and high-grade neoplasms
      accounted for 8 and 17 patients, respectively. 11 patients were aged 65 to 69
      years, while 14 were 70 years or older. Surgical margins were wide in 19 cases,
      marginal in 4, and intralesional in 2. Reconstruction was done using 6
      musculocutaneous flaps and/or 4 vessel grafts. As adjuvant therapy, radiotherapy
      was used in 5 cases and chemotherapy in 3. There was no recurrence in patients
      with wide surgical margins (determined on the basis of gross inspection of the
      excised tumour and the cut surface); but there was recurrence in 4 patients with
      marginal margins, and one patient with intralesional margin. Two patients with
      intralesional, 4 with marginal, and 2 with wide margins, died from recurrence at
      the primary site and metastasis, or from metastasis without recurrence at the
      primary site. RESULTS: Follow-up periods ranged from 4 months to 180 months
      (mean, 91.6 months). The overall 5-year survival rate was 79.6%; for low- and
      high-grade neoplasms, the figures were 100% and 69.7%, respectively; for those
      aged 65 to 69 years and in their 70's or older, the figures were 90.9% and 70.1%,
      respectively. CONCLUSION: For geriatric patients, wide surgical margins are
      required to manage both low- and high-grade neoplasms, in order to avoid multiple
      surgeries.

PMID- 12810969
TI  - Treatment of pathological fractures of the humerus with a locked intramedullary
      nail.
AB  - OBJECTIVE: The humerus is a common site for metastasis. Intramedullary nail
      fixation has been reported to be the best form of fixation for this disease but
      complications occur. This study aimed to assess the use of a new humeral nail to
      treat pathological fractures and impending pathological fractures of the humerus.
      METHODS: 29 patients received 31 Austofix locked intramedullary humeral nails: 25
      for pathological fractures and 6 for impending fractures; 24 nails were inserted
      anterograde and 7 retrograde. Cement augmentation was applied in 4 patients, and
      adjuvant therapy was used in 28 patients. Complications occurred in 12 patients.
      RESULTS: Fixation failed in 6 patients: 2 due to intraoperative fractures during
      retrograde nailing, one due to a fracture through screw holes postoperatively,
      and 3 due to local progression of disease. Difficulty in distal locking of the
      nail was encountered in 4 patients. Locked intramedullary nailing resulted in a
      stable humerus in 80% of patients. CONCLUSION: Retrograde insertion of the nail
      is associated with an increased risk of intra-operative fracture, and disease
      progression can occur, despite the administration of adjuvant therapy.

PMID- 12810970
TI  - Early results of posterior-stabilised NexGen Legacy total knee arthroplasty.
AB  - OBJECTIVE: To retrospectively assess the early results of the NexGen Legacy
      posterior-stabilised total knee prosthesis, which is a newer version of the
      Insall-Burstein II posterior-stabilised implant. METHODS: 48 consecutive elderly
      patients had 60 NexGen Legacy posterior-stabilised total knees. The mean follow
      up duration was 21 months. Clinical evaluation was performed according to the
      Knee Society scores and a scoring system for patellofemoral articulation;
      radiographic assessment followed the guidelines of the Knee Society. Special
      emphasis was given to any patellofemoral complications, such as patellar clunk
      syndrome, patellar maltracking, and other disorders of the extensor mechanism.
      RESULTS: Only one patient had mild patellofemoral anterior knee pain at the
      latest follow-up; 2 patients had patellofemoral crepitus but no pain. No patellar
      clunk or any other complication of the patellofemoral articulation, such as
      patellar fracture or subluxation was found. The mean preoperative and
      postoperative Knee Society scores were 60 and 85 respectively. The mean
      postoperative knee flexion was 115 degrees. CONCLUSION: The overall early results
      from using the new implant were good, probably because of changes in design of
      the intercondylar box and its associated cam-and-post mechanism, and a more
      anatomic trochlea surface, so that the trochlea accommodates the natural patella.

PMID- 12810971
TI  - Use of Wagner cementless self-locking stems for massive bone loss in hip
      arthroplasty.
AB  - OBJECTIVE: To assess the use of Wagner cementless self-locking stems for massive
      bone loss in hip arthroplasty. METHODS: 22 patients with severe proximal femoral
      bone loss either due to prosthetic loosening or comminuted fracture were treated
      by Wagner cementless self-locking revision stems between November 1993 and June
      1995. RESULTS: Radiographic evidence of early bony incorporation was found by 1
      month in most cases. At a mean follow-up of 7.1 years, the mean Harris hip score
      increased from 30 to 84 points. It was less than 80 points in 4 patients, 2 of
      whom experienced severe thigh pain due to marked progressive subsidence of the
      stems (by 13 mm and 20 mm), which were revised 2 and 3 years later respectively.
      CONCLUSION: Implantation of a Wagner cementless self-locking revision stem
      provided satisfactory results for 82% of patients. Hence, in some difficult
      conditions, this device is a good choice of management.

PMID- 12810972
TI  - Changes in proximal femoral bone mineral density around a hydroxyapatite-coated
      hip joint arthroplasty.
AB  - OBJECTIVE: To present the results of a prospective analysis of proximal femoral
      bone mineral density changes around a hydroxyapatite-coated total hip joint
      replacement. METHODS: 14 patients with osteoarthritis of the hip were enrolled in
      the study and treated with an uncemented ABG prosthesis. Dual energy X-ray
      absorptiometry scanning was performed in 9 patients preoperatively, and at 3, 6,
      12, and 24 months postoperatively. An orthopaedic software program was used to
      determine the bone mineral density in the proximal femur, expressed as a
      percentage of the preoperative value. RESULTS: The values of Gruen zones 1 to 6
      averaged between 96.0% and 113.8% of the preoperative value by 24 months (overall
      average, 104.1%). In zone 7, however, there was a gradual decline in bone mineral
      density to an average of 72.1% of the preoperative value by 24 months. This
      represented ongoing loss of bone from the calcar; although this may not pose a
      problem to the prosthetic's short-term stability, it may render potential
      revision surgery more difficult. CONCLUSION: The initial outcome of uncemented
      total hip replacement appears to be promising. There was excellent maintenance of
      bone around the femoral component in all regions other than the calcar and lesser
      trochanter. Further scans are required to see if these trends continue in the
      long term.

PMID- 12810973
TI  - The shape and size of femoral components in revision total hip arthroplasty among
      Chinese patients.
AB  - OBJECTIVE: 39 sets of preoperative hip X-rays were studied to find out whether
      Chinese patients need revision femoral components with a different shape and size
      from western patients. METHODS: From July 1998 to June 2001, the pre-revision X
      rays of 39 revision total hip replacements among 38 Chinese patients (21 men and
      17 women) were studied. The component size that produced the best distal canal
      filling in the anteroposterior X-ray was determined by using templates of 200-mm
      femoral components used commonly for Caucasian patients. RESULTS: The diameter of
      the component needed was 13.5 mm or less in 54% of cases, compared with only 17%
      for Caucasian patients as reported in the literature (p<0.01). When lateral
      templates of the corresponding size were put over the lateral X-rays, the
      anterior cortex of the 200-mm straight stem was shown to have thinned by 2.0 mm
      or more in 36% of hips; for 200-mm bowed stem, there was thinning of the anterior
      cortex by 2.0 mm or more in only 5% of hips (p<0.01). CONCLUSION: Chinese
      patients are likely to need smaller femoral components than Caucasian patients,
      and may benefit from bowed-stem components in femoral revision.

PMID- 12810974
TI  - Stabilisation of fractured thoracic and lumbar spine with Cotrel-Dubousset
      instrument.
AB  - OBJECTIVE: To evaluate the effectiveness of 2 different types of Cotrel-Dubousset
      instrument systems in stabilising thoracolumbar and lumbar spine fractures.
      METHODS: Between January 1989 and December 1993, 45 fractures in 42 patients with
      unstable fracture or fracture dislocation of the thoracolumbar and lumbar spines
      were randomly assigned to 2 surgical treatments with Cotrel-Dubousset
      instrumentation-using either a long segment (Group 1) or a short segment (Group
      2)-and short posterolateral fusion. RESULTS: Consolidation of the fractured
      vertebral body and posterolateral fusion were achieved at a mean time of 4.5
      months; fusion rates were 75% in Group 1 and 83% in Group 2. The average
      collapses of anterior vertebral body height in Group 1, in the immediate
      postoperative period and at the final follow-up, were 15% and 17%, respectively;
      and in Group 2, the figures were 16% and 24%, respectively. The correction of
      vertebral height and kyphosis at the last follow-up were lost more in Group 2
      (5.7 degrees ) than in Group 1 (4.4 degrees ). There were neurological recoveries
      in 6 of the 9 cases of incomplete paraplegics, including complete recovery in 5,
      and one-Frankel grade increase in one. There were 15 instrument failures in 12
      patients, including screw breakage in 3 Group 1 cases and 6 Group 2 cases. The
      plug dislodged in 3 Group 1 cases, and the hook dislodged in 3 Group 2 cases. In
      other words, instrument failures were more common in Group 2. CONCLUSION: Cotrel
      Dubousset stabilisation of the fractured spine achieves fracture consolidation,
      but does not maintain the restored height and sagittal curve completely until
      fusion. The long rod and short fusion construct was more effective for all
      fracture types than was the short rod and fusion construct, although it leads to
      wider immobilisation of normal segments.

PMID- 12810975
TI  - Use of epidural analgesia for pain management after major spinal surgery.
AB  - OBJECTIVE: This is a retrospective study of the role of postoperative epidural
      analgesia in major spinal surgical procedures. With the number and complexity of
      the procedures performed on the spine ever-increasing, this method of analgesia
      is becoming more important. METHODS: Results of 74 consecutive cases of major
      spinal surgeries between January 2000 and January 2001 at the Spine Division,
      Amritha Institute of Medical Sciences and Research Centre, Kochi, India, were
      studied. 32 cases were posterior procedures and the other 42 were anterior
      procedures of the thoracic and lumbar regions. The use of various combinations of
      local anaesthetic and opioid to control postoperative pain after spinal surgery
      were analysed. RESULTS: 36 (49%) of 74 patients did not require any parenteral
      supplements. Of the remaining 38 patients who required supplementary parenteral
      analgesia in the first 48 hours, 25 (34%) received a single dose and 13 (18%)
      required more than one dose. The number of patients requiring parenteral
      analgesia immediately after operation were 11; between 2 and 6 hours were 12; and
      between 6 and 24 hours were 11. Of the 74 patients, 67 had a sound sleep after
      epidural administration. There were 2 cases of respiratory depression and 2 of
      transient hypotension. CONCLUSION: Most epidural analgesic regimens significantly
      reduced postoperative pain, and the requirement for supplementary parenteral
      analgesics was minimal. Adverse effects were rare, yet we recommend that patients
      treated with this protocol be managed in high-dependency units.

PMID- 12810976
TI  - Use of antibiotic-loaded polymethyl methacrylate beads in the management of
      musculoskeletal sepsis--a retrospective study.
AB  - OBJECTIVE: To assess the use of antibiotic-loaded polymethyl methacrylate beads
      in the management of chronic osteomyelitis of different aetiologies: infected
      osteosynthesis, infected open fractures, and haematogenous osteomyelitis.
      METHODS: Records of 49 patients with chronic osteomyelitis who were treated at
      Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were
      studied retrospectively. The diagnosis of chronic osteomyelitis was made on the
      basis of clinical and radiographic features. Of the 49 patients, 4 had
      haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus
      excluded. Antibiotic-loaded acrylic beads were implanted in the remaining
      patients after thorough debridement. The implant was removed primarily in 16
      patients with infected osteosynthesis, who then underwent decompression and
      sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were
      given for 7 days. Beads were removed at the end of 3 weeks followed by bone
      grafting in 26 patients. Patients were followed up for an average period of 3.7
      years. RESULTS: The infective organisms were sensitive to gentamycin in 26 cases
      and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to
      cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant
      to all antibiotics tested. Of the 19 patients with gentamycin-resistant
      infection, only one had a poor result. No adverse systemic side-effects such as
      ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients,
      but 6 patients had low-grade persistent infection at the last follow-up visit.
      CONCLUSION: In chronic infections, especially those following osteosynthesis,
      antibiotic beads are a valuable adjuvant. The most valuable advantage is that the
      wound can be closed primarily, thereby reducing the incidence of nosocomial
      infections and requirement of nursing care.

PMID- 12810977
TI  - Decreased access to health care and social isolation among young adults with
      cerebral palsy after leaving school.
AB  - OBJECTIVE: To examine if leaving special schools has a negative impact on the
      health care and social isolation of young adults with cerebral palsy. METHODS:
      Young adults with cerebral palsy, aged between 15 and 22 years, were divided into
      2 cohorts: current students, who were still receiving services from special
      schools, and school-leavers, who had since been discharged from care. A
      questionnaire and physical examination were administered to assess the extent of
      disability, health care received by, and social isolation of these young adults.
      RESULTS: School-leavers had a greater degree of dissability than did students,
      although the results were not statistically significant. Health care exposure to
      specialists, general practitioners, therapists physiotherapists, occupational
      therapists, and/or speech therapists), and medical social workers decreased after
      leaving school; with the exception of contact with general practitioners, these
      results were significant (p<0.05). The entire cohort was more socially isolated
      than a control cohort. School-leavers participated in fewer activities outside
      their homes, but showed less concern about their disability than did current
      students. CONCLUSIONS: Young adults with cerebral palsy continue to have health
      care and lifestyle needs after leaving school, which are currently not being
      adequately met.

PMID- 12810978
TI  - Radiotherapy for desmoplastic fibroma of bone: a case report.
AB  - Desmoplastic fibroma is a rare benign tumour of bone. Diagnosis is not easy and
      is often made by excluding other tumours. Histopathological diagnosis of this
      tumour is also sometimes not easy. The treatment modalities for this tumour are
      non-uniform and often controversial. In the present case surgical options were
      left aside because the patient did not consent to surgery, so radiotherapy was
      used, with success at 3-year follow-up. This case is presented here along with a
      review of relevant literature.

PMID- 12810979
TI  - Implantation metastasis in a 13-year-old girl: a case report.
AB  - We report a case of a 13-year-old girl with an osteosarcoma of the right humerus,
      which had been diagnosed as an aneurysmal bone cyst at our institution. She
      underwent curettage and bone grafting of the lesion, which resulted in
      implantation metastasis of the tumour to the ilium. She died 15 months after
      presentation owing to pulmonary metastases. This report highlights the
      possibility of metastasis occurring by direct implantation to a graft donor site.
      We strongly recommend that a biopsy be performed in cases of presumed benign
      lesions before proceeding with the definitive surgery.

PMID- 12810980
TI  - Use of bisphosphonate to manage avulsion fracture of tibial tuberosity with
      underlying angiomatosis: a case report.
AB  - An unusual case of avulsion fracture of the tibial tuberosity with underlying
      angiomatosis in a middle-aged man is described, with particular emphasis on the
      successful use of bisphosphonate in its treatment and the value of serial dual
      energy X-ray absorptiometry in its subsequent disease monitoring. This case
      illustrates the importance of careful correlation of the clinical, radiological,
      and histological findings in the management of skeletal tumour and tumour-like
      lesions. The differential diagnosis of osteolysis with vascular ectasia is
      discussed.

PMID- 12810981
TI  - [Monogenic causes of nonspecific X-linked mental retardation molecular aspects].
AB  - Mental retardation (MR) is a symptom in a large group of clinical conditions and
      affects around 3% of the population. MR is divided into syndromic, if it is
      characterized by distinctive clinical features and nonspecific when mental
      retardation is the only defining manifestation. Although genetic causes of X
      linked mental retardation (XLMR) are heterogenous and complex, recent findings
      have led to the identification of an increasing number of genes involved in these
      conditions. Eight genes involved in nonspecific X-linked mental retardation have
      been identified so far, including FMR2, GDI1, OPHN1, PAK3, ARHGEF6, IL1RAPL,
      TM4SF2, and FACL4. Four other MECP2, RSK2, ARX, ATR-X are involved in syndromic
      and nonspecific forms of MR. Recent research has shown that these genes encode
      for proteins involved in signaling pathways which regulate cytoskeleton
      organization, synaptic vesicle transport and establishment of connections between
      neuronal cells. These findings provide insight into the molecular mechanisms of
      crucial processes for the development of intellectual and cognitive functions.

PMID- 12810982
TI  - [Molecular pathogenesis of fragile X syndrome].
AB  - The fragile X syndrome is an X-linked genetic disorder; manifesting primarily as
      intellectual disability. The disease is caused by the absence of functional FMRP,
      a protein encoded by the FMR1 gene. The expansion of trinucleotide repeats within
      the first exon of the gene contributes to most cases of the syndrome. This review
      summarizes the present knowledge of the relationship between the molecular defect
      in the FMR1 gene and the clinical phenotype associated with disease.

PMID- 12810983
TI  - [The principles of molecular diagnosis of recessive forms of prelingual non
      syndromic hearing loss].
AB  - The GJB2 gene defects are the most frequent cause of autosomal recessive non
      syndromic hearing loss (DFNB1). Epidemiological data suggest that 35delG is the
      most prevalent mutation found in 88% of mutated alleles. Another mutations -
      313del14 was found in 7% of mutated alleles. The other mutations were identified
      only in single families. Following the analysis of distribution of GJB2 mutations
      in the Polish population we propose an algorithm for molecular diagnosis of
      DFNB1. We propose to screen all patients affected with prelingual non-syndromic
      deafness for 35delG mutation using ASO or multiplex AS-PCR methods. The presence
      of 35delG on two alleles confirms DFNB1. The identification of heterozygous
      35delG mutation requires additional GJB2 analysis including 313del14 mutation
      detection and en exon 2 direct sequencing. To determinate the frequency of
      digenic (GJB2/GJB6) background of DFNB we screened 17 patients with heterozygous
      35delG mutation for deletion of 342 kb in GJB6 gene. No such mutation was
      detected in the analyzed group.

PMID- 12810984
TI  - [Identification of T274I mutation in the SMN1 gene in a patient with spinal
      muscular atrophy].
AB  - Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular
      disorder characterised by degeneration of motor neurones in the spinal cord. The
      symptoms of the disease are determinated by mutations of SMN1 gene. About 98% of
      SMA patients show homozygous absence of exon 7 SMN1 gene, the rest carry small
      intragenic mutations. Molecular analysis of the presence of exon 7 SMN1 gene
      deletion is considered as the screening test for SMA. We present a case report of
      a 9 years old girl with progressive muscular weakness of limbs and trunk.
      Clinical examination followed by electromyography and muscle biopsy was
      interpreted as a diagnostic of SMA 3. Molecular analysis did not reveal deletion
      of exon 7 SMN1 gene. Extended molecular diagnostics using direct sequencing
      showed missence mutation T2741. Thus, the absence of homozygous deletion of exon
      7 SMN1 gene does not exclude SMA diagnosis. All patients fulfilling the
      diagnostic criteria for SMA, as defined by the International SMA Consortium,
      without deletion of exon SMN1 gene, should be analysed using direct sequencing.

PMID- 12810985
TI  - [Clinical expression of triploidy].
AB  - Triploidy, the presence of an additional haploid set of chromosomes, is the cause
      of 20% of spontaneous abortions, premature births and perinatal deaths. The most
      common clinical signs of triploidy are: severe intrauterine growth retardation,
      macrocephaly, total syndactyly of third and fourth fingers and CNS, heart and
      renal defects. Hydatidiform mole, one of the characteristic features of pure
      triploidy, is found in more than 90% of cases. The survival of individuals with
      diploid/triploid mixoploidy is usually longer than of those with pure triploidy.
      The detailed clinical characteristics of two of our patients with triploidy
      diagnosed shortly after birth are presented. In one of them mixoploidy
      (lymphocytes/fibroblasts) was confirmed. In the second pure triploidy was
      identified in cultured lymphocytes. We discuss the clinical features in our
      patients and compare them with data from medical literature.

PMID- 12810986
TI  - [Genetically determined male infertility caused by the CFTR gene mutations].
AB  - One of the reasons for the genetically determined male infertility is congenital
      bilateral absence of the vas deferens (CBAVD). CBAVD until recently classified as
      a separate disease, is now recognised to be a form of atypical CF (cystic
      fibrosis). The above is based on the fact that both CF and CBAVD result from
      mutations in the same CFTR gene. Assisted reproduction techniques (ART),
      including the ICSI (IntraCytoplasmic Sperm Injection) technique, is an
      acknowledged chance of having offspring for males with extremely bad semen
      quantitative parameters, including CBAVD patients. Molecular analysis of the CFTR
      gene along with genetic counselling enables to estimate the risk of having
      offspring with classical or atypical CF after ICSI procedure.

PMID- 12810987
TI  - [Genetic risk factors of neural tube defects].
AB  - Neural tube defects (NTDs) are a group of diseases caused by a failure of closure
      of the neural tube. Its aetiology contains both environmental and genetic
      factors. NTDs have a polygenic background. Genes, which are linked with NTDs
      occurrence, are both directly and indirectly connected with controlling the
      process of closure of the neural tube. Ones of those are genes of metabolism of
      folic acid as MTHFR, MTR, MTRR, CBS, MTHFD, folic acid receptors (FR) regulator
      genes from PAX family, T, PDGFRA and BRCA1 genes.

PMID- 12810988
TI  - [Mutations of MTHFR, MTR, MTRR genes as high risk factors for neural tube
      defects].
AB  - Neural tube defects (NTDs) have a polygenic background. There are numerous genes
      known to be high-risk genetic factors for NTDs. Ones of them are mutations of
      foliate metabolisms pathways genes. This paper shows the results of analysis of
      common mutations of MTHFR, MTR and MTRR genes. Results of screening mutations
      2756A-->G and 66A-->G in MTR and MTRR genes respectively show that are might have
      an effect on NTDs incidence among the examined population. Analysis of data for
      the studied population does not prove the influence of mutations 677C-->T and
      1298A-->C of MTHFR gene on NTDs.

PMID- 12810989
TI  - Vitamin D and the skin.
AB  - Vitamin D was originally discovered as a factor that regulates calcium and bone
      metabolism. Recent advances in investigation have shown that vitamin D also
      functions as a regulator of cellular growth and differentiation in various
      tissues. The skin is not an exception from such effects of vitamin D; it is
      regarded as a site of its activation and action. Evidence has accumulated showing
      that the active form of vitamin D and its analogs suppress growth and stimulate
      the terminal differentiation of keratinocytes. In psoriatic lesions, epidermal
      keratinocytes exhibit hyper-proliferation and impaired differentiation triggered
      by inflammation. Therefore, it is quite reasonable that vitamin D is effective on
      psoriasis. Indeed, within the past decade, analogs of vitamin D3 have been used
      as topical therapy for psoriasis. In this review, we summarize the fundamental
      features of vitamin D and the development of vitamin D therapy for psoriasis.
      Clinical application to other skin diseases and the future of vitamin D therapy
      in dermatology are also discussed.

PMID- 12810990
TI  - Cutaneous concerns of scleroderma patients.
AB  - The clinical features of facial and oral involvement in scleroderma are striking.
      We conducted a survey of patients with systemic sclerosis (scleroderma). The
      purpose of our study was to ascertain what was most bothersome aesthetically to
      scleroderma patients. We also looked at the differences between age groups and
      genders. The survey was mailed to 1,000 individuals who subscribe to a national
      lay group organization. We received 303 completed surveys indicating the
      patient's age, gender, age at onset of disease, and a checklist of 14 physical
      variables involving the central face and non-face. The respondents were asked to
      rate their level of concern [on a scale of great (1) -moderate (2) -little (3) 
      none (4)] in regards to 14 different physical variables. The respondents
      consisted of 92% females and 8% males. The mean age was 59 years +/- 13 (SD), and
      the median age was 60. The mean and median age at diagnosis was 45 years +/- 15
      (SD). The percentage of respondents expressing concern for specific features was
      the following: for thin lips (73%), mouth furrows (80%), loss of facial lines
      (68%), and a smaller, tighter mouth (77%). There was less concern over the non
      face features. The percentage of respondents expressing no concern was the
      following: for absence of sweating (57%), skin darkening (50%), nail dystrophy
      (57%), and skin atrophy (63%). There was a highly statistically significant
      difference (p<0.0001) between those respondents concerned with central face
      features vs. non-face features. With advancing age and longer disease duration,
      there was increased concern over the aforementioned central face features
      (p<0.0001). The vast majority of patients with systemic sclerosis have great
      concerns over changing facial features, and this worsens with age.

PMID- 12810992
TI  - Treatment of persistent severe atopic dermatitis in 113 Japanese patients with
      oral psoralen photo-chemotherapy.
AB  - Oral administration of psoralen and whole body exposure to UVA (oral PUVA) has
      been used for the treatment of 113 patients with severe atopic dermatitis (AD). 8
      Methoxypsoralen (8-MOP) was given at a dose of 0.5-0.6 mg/kg two hours prior to
      UVA (3-8 J/cm2) irradiation. Patients were treated three times a week while
      hospitalized. Other medications which had been given before PUVA therapy were
      permitted. At four and eight weeks after PUVA therapy, the severity score of AD
      had decreased by 51% and 80%, and the cumulative doses of UVA were 51.2 J/cm2 and
      115.3 J/cm2, respectively. The amounts and strength of topical cortico-steroids
      were decreased during PUVA therapy. No adverse effects that required
      discontinuation of the PUVA therapy were observed. After discharge, maintenance
      therapy with UVB phototherapy and/or conventional treatment of AD kept the
      patients in remission in the outpatient clinic. The QOL of patients was greatly
      improved. Photochemotherapy with oral 8-MOP can be indicated in patients with
      severe, widespread AD, especially if standard therapy fails. This is the first
      report of oral PUVA therapy in a large series of Japanese patients with AD.

PMID- 12810991
TI  - Effectiveness of iontophoresis with alternating current (AC) in the treatment of
      patients with palmoplantar hyperhidrosis.
AB  - Conventionally, iontophoresis employing direct current (DC) has been used in the
      treatment of palmoplantar hyperhidrosis, but this is accompanied by side effects
      such as pain and burns. In the present study, a prototype apparatus using
      alternating current (AC) was constructed, and iontophoresis with AC was performed
      in palmoplantar hyperhidrosis patients to determine its effectiveness. The
      average amount of perspiration of the palmoplantar hyperhidrosis patients was
      significantly reduced after the third session when iontophoresis treatments were
      performed once per week. By the eighth treatment, perspiration was reduced to
      nearly the normal level, and there were no particular side-effects during the
      treatment period. This treatment therefore appears to be both safe and effective.
      The treatment effect tended to appear sooner when alternating current
      iontophoresis was combined with the administration of anticholinergic drugs than
      when alternating current iontophoresis was used alone. Alternating current
      iontophoresis is an effective treatment for palmoplantar hyperhidrosis.
      Guidelines for this treatment for patients with palmoplantar hyperhidrosis will
      need to be established in the future.

PMID- 12810993
TI  - Efficacy and safety of cyclosporine versus methotrexate in severe psoriasis: a
      study from north India.
AB  - Treatment of patients with severe psoriasis is difficult. Among the number of
      systemic drugs that are available, methotrexate has long been used, but
      cyclosporine has been recently recommended for the management of severe
      psoriasis. The purpose of this study was to compare the efficacy and safety of
      daily cyclosporine with weekly methotrexate in the management of severe
      psoriasis. Thirty consecutive patients with severe psoriasis were randomly
      assigned to treatment with cyclosporine or methotrexate. The initial dose of
      cyclosporine was 3 mg/kg/day, which was increased to a maximum of 4 mg/kg after
      two weeks of therapy when the response was not adequate. Methotrexate was
      administered weekly at a dose of 0.5 mg/kg. Clinical response was assessed by
      calculating PASI score in all patients at biweekly intervals. Patients were
      followed up fortnightly up to a maximum of 12 weeks. The doses of both drugs were
      gradually tapered once >75% reduction in disease severity was attained. Marked
      improvement (>75%) reduction in PASI was noted in all patients except for one in
      the cyclosporine group. The median time for marked improvement was 5.3 weeks with
      methotrexate and 6.8 weeks with cyclosporine. Patients on methotrexate were found
      to have more rapid and complete clearance than those on cyclosporine. Both drugs
      were well tolerated. Side effects in both the treatment groups were minor,
      transient, and manageable. At doses with comparable safety profiles, methotrexate
      resulted in more rapid and cost effective clearance of patients with severe
      psoriasis. Cyclosporine can provide an effective and safe alternative.

PMID- 12810994
TI  - Acetylator phenotype in Behcet's disease.
AB  - The purpose of this study was to determine the acetylator status in Behcet's
      disease (BD) patients and compare it to a matched group of normal individuals.
      Thirty-seven healthy volunteers and forty-one BD patients were included. Detailed
      history was taken from the patients. HLA-B51 was determined in the BD patients.
      In addition, the Clinical Manifestation Index (C.M.I.) was determined for each
      patient. Pathergy test was also done. After an overnight fast, each control
      subject and patient received a single oral dose of 100 mg of DDS. A blood sample
      was collected after 3 hours and the plasma was separated for determination of
      dapsone/monoacetyldapsone by HPLC. The frequency of slow acetylators in healthy
      individuals was 70.2%, while the frequency of rapid acetylators was 29.8%. The
      frequency of slow acetylators in BD patients was 53.7%, while the frequency of
      non-acetylators (undetected monoacetyldapsone MADDS in plasma) was 46.3%. There
      were no rapid acetylators among the BD patients. There was a strong negative
      association between the acetylator status and the severity of BD. In addition,
      acetylator status correlated with HLA-B51, in that BD patients with positive HLA
      B51 were characterized by a very slow or non-acetylator status. Slow or non
      acetylators had more severe BD. We conclude that BD patients have a unique
      acetylator status. This finding may have implications for the theories for the
      pathogenesis of the disease as well as for therapeutic aspects.

PMID- 12810995
TI  - Superficial granulomatous pyoderma: a case report of two Japanese patients and
      clinical comparison with foreign patients.
AB  - Superficial granulomatous pyoderma (SGP) is an unusual variant type of pyoderma
      gangrenosum characterized by a benign course and specific histological features;
      it is quite a rare cutaneous disorder in Japan. We reported two Japanese cases of
      SGP and compared the clinical features of 13 Japanese cases with those of 42
      foreign cases. Case 1 was a 53-year-old female who presented with three indolent
      and ulcerative plaques with elevated edges on the back and the posterior portion
      of the left thigh. Case 2 was a 74-year-old female who presented with crusted and
      vegetative erythematous plaques on the left shoulder and left upper arm.
      Histological examinations revealed a characteristic three-layer granuloma in each
      case. Laboratory and physical examinations found no abnormalities. Topical
      corticosteroid, oral administration of minocycline, and/or additional
      supplementation with corticosteroid were effective. In comparison with foreign
      cases, Japanese cases show a possible differentiation in the ratio of sex and
      distribution of the ulcer. Females have a high incidence and the extremities are
      frequently involved area in Japanese cases. Up to now, 11 cases of SGP have been
      reported in Japan. To our best knowledge, our patients are the first Japanese
      cases described in the English literature.

PMID- 12810996
TI  - A giant cystic hygroma on the leg of a newborn infant complicated by
      hyponatremia.
AB  - Cystic hygromas are large cystic masses resulting from failure of lymph drainage.
      The vast majority occur in the neck or axilla. Cases of cystic hygroma of the
      extremity are extremely rare. We present a newborn infant with a giant cystic
      hygroma on her left leg, complicated by severe hyponatremia.

PMID- 12810997
TI  - Cutaneous metaplastic synovial cyst.
AB  - Metaplastic synovial cyst of the skin is a recently recognized entity
      characterized by an intradermal nodule that usually occurs at the site of
      previous surgical trauma. Histologically, the lesion demonstrates a cystic
      structure with villous-like projections and a lining resembling hyperplastic
      synovium. We have studied two patients with rheumatoid arthritis, aged 46 and 55
      years, who presented with cystic nodules localized on the thumb and great toes,
      respectively, without any history of previous trauma or surgical procedures
      performed in the areas. The presence of vimentin and CD 68 positivity of the
      cells lining the cyst walls supports the similarities between normal and
      metaplastic synovium. We hypothesize that constant pressure on the great toe,
      repeated manipulation of the finger, and chronic inflammation around the affected
      joints may have played roles in the pathogenesis of the lesions in our patients.

PMID- 12810998
TI  - Disseminated Mycobacterium chelonae cutaneous infection: recalcitrant to combined
      antibiotic therapy.
AB  - A 25-year-old Thai housewife had a history of tuberculosis of the lymph nodes for
      six years that had been successfully treated with a course of anti-TB drugs. She
      developed several red, circumscribed, infiltrative plaques composed of
      umbilicated papules and pustules on her face and upper part of the body with
      cervical lymphadenopathy six months later. A pus smear from the lesion grew acid
      fast bacilli (AFB). Histopathological examination showed a mixed cell granuloma
      suggestive of infection. A T cell study showed a low CD4 count, and multi skin
      tests indicated cutaneous anergy. Culture from a biopsy specimen taken from the
      skin lesion grew M.chelonae; the cultures from blood, urine, and bone marrow. The
      lesions were not responsive to an anti TB drug given for 2 months based upon the
      results of the AFB positive pus smear before the culture and sensitivity reports
      were obtained. Since then the patient was treated with antibiotics according to
      the results of the sensitivity tests. A combination of amikacin and
      clarithromycin was started and hyperthermic therapy was later added with a
      partial response. Based upon the sensitivity test, kanamycin was introduced but
      had to be stopped because of ototoxicity. Sparfloxacin was used with an effective
      result but was discontinued for economic reasons. Finally, clarithromycin in
      combination with clofazimine and cryotherapy were given for a year before the
      lesions healed completely. It took a three years duration for the total course of
      treatment for this patient. She is still in remission after two years of follow
      up period. This extensive cutaneous M.chelonae infection needed a prolonged
      combination of antibiotics with the addition of cryotherapy for the non
      responsive lesions.

PMID- 12810999
TI  - Subungual extraskeletal chondroma mimicking glomus tumor.

PMID- 12811000
TI  - A cochlear cell line as an in vitro system for drug ototoxicity screening.
AB  - Aminoglycoside antibiotics, loop diuretics, antineoplastic agents and other
      commonly used pharmacological drugs are ototoxic. Understanding of the cellular
      and molecular mechanisms underlying drug ototoxicity, however, has been hampered
      by the limited availability of inner ear tissues and drug side effects on
      laboratory animals. Immortalized cell lines derived from the auditory sensory
      organ, sensitive to ototoxic drugs and growing in environments that can be
      systematically manipulated, would facilitate the research directed at elucidating
      these mechanisms. Such immortalized cell lines could also be used to discover
      novel therapeutic agents for preventing drug-induced sensorineural hearing loss.
      Here, we report a conditionally immortalized organ of Corti-derived epithelial
      cell line, which shows evidence of activation of apoptosis when exposed to known
      ototoxic drugs. This cell line may be an excellent in vitro system to investigate
      the cellular and molecular mechanisms involved in ototoxicity and for screening
      of the potential ototoxicity or otoprotective properties of new pharmacological
      drugs.

PMID- 12811001
TI  - Molecular plasticity in the rat auditory brainstem: modulation of expression and
      distribution of phosphoserine, phospho-CREB and TrkB after noise trauma.
AB  - We induced acoustic trauma by applying click stimuli of 130 dB (SPL) for 30 min
      to one ear of adult rats. This treatment resulted in an instant and permanent
      threshold shift of 96 dB in the affected ear. A massive reduction of cochlear
      nerve fibers in the ventral cochlear nucleus (VCN) was demonstrated by tracing
      them from the cochlea of rats that survived acoustic overstimulation for 1 year
      or longer. In the auditory brainstem, we observed a deprivation-dependent
      appearance of fibers positive for tyrosine receptor kinase B in the ipsilateral
      VCN between day 3 and day 21 after trauma and an increase in phosphoserine
      immunostaining in the neuropil of the ipsilateral VCN and in neurons of the
      contralateral lateral superior olive during the first 30 days after trauma.
      Immunoreactivity for the cAMP response element binding protein in its
      phosphorylated form was transiently depressed in the ipsilateral inferior
      colliculus immediately after trauma and was elevated as late as 7 months after
      trauma in the ipsilateral VCN. Apparently, a unilateral acoustic overstimulation
      entails specific regulations of the activity of plasticity-associated molecules
      through phosphorylation and includes changes to neurotrophin signaling between
      neurons of the auditory brainstem.

PMID- 12811002
TI  - 8-iso-prostaglandin F(2alpha), a product of noise exposure, reduces inner ear
      blood flow.
AB  - Noise exposure induces the formation in the cochlea of 8-isoprostaglandin
      F(2alpha) (8-iso-PGF(2alpha)), a marker for reactive oxygen species [Ohinata et
      al., 2000a] and a potent vasoconstrictor, raising the possibility that 8-iso
      PGF(2alpha) may be responsible for noise-induced reductions in cochlear blood
      flow (CBF). To test this hypothesis, CBF was assessed in the guinea pig in
      response to 'local' (via the anterior inferior cerebellar artery) and systemic
      (i.v.) delivery of 8-iso-PGF(2alpha) using laser Doppler flowmetry. Local 8-iso
      PGF(2alpha) induced a clear reduction in CBF. With systemic infusion, vascular
      conductance (VC), the ratio of CBF to systemic blood pressure, decreased in a
      dose-dependent manner up to 30%, consistent with an 8-iso-PGF(2alpha)-induced
      constriction of the cochlear vasculature. Infusion of SQ29548, a specific
      antagonist of 8-iso-PGF(2alpha), appropriately blocked an 8-iso-PGF(2alpha)
      induced CBF response. Similarly, noise-induced changes in CBF and VC were
      prevented by infusion of SQ29548 during noise exposure or by antioxidant
      treatment (glutathione monoethyl ester) prior to exposure. Prevention of
      isoprostane-mediated vasoconstriction may have clinical utility in the protection
      from noise-induced hearing loss.

PMID- 12811003
TI  - Single-dipole analyses of the N100m are not suitable for characterizing the
      cortical representation of pitch.
AB  - In several previous studies, the deflection N100m of the auditory evoked field
      (AEF), occurring about 100 ms after the onset of a sound, has been used to
      investigate whether complex tones are represented in the auditory cortex by their
      spectrum or their periodicity pitch. However, the results partially contradict
      each other. Moreover, the basic assumption that N100m originates from a single
      cortical source has been questioned. To gain clarity, the AEF elicited by a
      complex tone with a periodicity of 4 ms (pitch 250 Hz) and a spectrum between
      1000 and 2000 Hz was compared with the AEF in response to pure tones of 250 and
      1000 Hz, respectively (on 12 subjects). While a previous analysis [Audiol
      Neurootol 2001;6: 263-278] was exclusively devoted to the N100m latency, this
      article presents source analyses with two variants of a single-dipole model
      (moving dipole and fixed dipole). Earlier reports, suggesting that N100m arises
      from a cortical source representing the pitch rather than the spectrum of the
      sound, could not be reproduced, independent of the method used. It appears that
      an investigation of the functional organization of the human auditory cortex
      based on N100m source modeling requires a much higher degree of sophistication
      than a single-dipole model can provide.

PMID- 12811004
TI  - A paradigm to measure mismatch negativity responses to phonetic and acoustic
      changes in parallel.
AB  - The mismatch negativity (MMN) of the event-related potential has been purported
      to be an objective index of central auditory processing. The present study tested
      a new paradigm to measure the MMN responses to phonological changes in parallel
      with those to simple acoustic changes. Stimulus sequences consisted of repetitive
      consonant-vowel syllables interspersed with infrequent phonetic changes (in place
      of articulation or voicing) and repetitive sinusoidal tones with occasional
      acoustic changes (in frequency or duration). The speech and tone stimuli were
      delivered to the opposite ears (right and left, respectively) at a stimulus onset
      asynchrony (SOA) of 300 ms. The MMNs elicited in this new paradigm were compared
      with those measured in a conventional paradigm, in which the speech and tone
      stimuli were presented in separate sequences at an identical speech-speech or
      tone-tone SOA (600 ms) of the new paradigm. The MMNs elicited in the two
      paradigms had a similar morphology and topography, although the MMNs measured
      with the new paradigm were slightly smaller for 3 out of 4 types of deviants. The
      results suggest that the new paradigm enables the measurement of reliable MMNs to
      phonetic changes in parallel with those to acoustic changes.

PMID- 12811005
TI  - Current developments in antithrombotic therapy: the role of antithrombin agents.
AB  - Hirudin, the specific thrombin inhibitor from medicinal leeches, is now produced
      by recombinant technology. r-Hirudin and to a lesser extent polyethyleneglycol
      coupled hirudin (PEG-hirudin) have been used in many clinical trials. Hirudin has
      been shown to be more effective than low molecular weight heparin in the
      prevention of deep venous thrombosis after total hip replacement. In (acute)
      coronary syndromes hirudin as well as a synthetic hirudin analogue bivalirudin
      have been studied in large clinical trials. Higher doses of hirudin were
      associated with an increased risk of bleeding. A large-scale study with
      bivalirudin in patients with acute MI (the HERO-2 trial) has not shown a
      reduction in mortality but a 30% reduction of reinfarction within 96 h. Hirudin
      and argatroban have been successfully used in patients with heparin-induced
      thrombocytopenia type II. Several orally active thrombin inhibitors are being
      developed. The combined use of subcutaneous and oral administration of melagatran
      in patients with hip or knee replacement has led to promising results. It is
      likely that in the future thrombin inhibitors will replace other forms of
      anticoagulation in a number of indications.

PMID- 12811006
TI  - An overview of the direct thrombin inhibitor argatroban.
AB  - Argatroban is a small molecule direct thrombin inhibitor. The main attributes of
      this synthetic drug are its rapid onset of anti-thrombin action, rapid
      reversibility of its anticoagulant effect, potent inhibition of clot-bound
      thrombin, absence of antibody formation and no need for initial dosage adjustment
      in patients with renal impairment. It is eliminated by hepatic metabolism. These
      properties make argatroban a predictable anticoagulant with intravenous use in a
      routine clinical setting. Argatroban is approved in the US and Canada for both
      prophylaxis and treatment of thrombosis in patients with heparin-induced
      thrombocytopenia (HIT); and it is approved in Japan and Korea for treatment of
      various thrombotic disorders. Argatroban has been shown in limited trials to
      provide reliable anticoagulation during percutaneous coronary interventions on
      HIT and non-HIT patients. Preliminary reports document the feasibility of using
      argatroban for anticoagulation during peripheral vascular interventions,
      hemodialysis and as adjunct to thrombolysis for treatment of myocardial
      infarction. Current recommendations for argatroban monitoring are to use the
      activated partial thromboplastin time for low doses and the activated clotting
      time for high doses. The ease of monitoring argatroban, its 'turn-on/turn-off'
      characteristic and its consistent safety profile provide the rationale to
      continue studies of argatroban as an anticoagulant in clinical settings.

PMID- 12811007
TI  - Historical perspective of the development of thrombin inhibitors.
AB  - Progress in molecular biology has stimulated interest in the structure and
      function of thrombin. It has improved our understanding of its central role in
      thrombogenesis and has clarified the molecular events of inhibitor binding. This
      development has resulted in the production of recombinant hirudins and hirudin
      analogues. It has also allowed the molecular design of synthetic antithrombins,
      and encouraged the development of these products for clinical use. All
      pharmacological aspects speak in favor of the use of direct thrombin inhibitors
      as antithrombotic agents, especially in the potential indications where thrombin
      plays a crucial pathogenetic role. If their apparent advantages compared with
      heparin can be definitely demonstrated, the direct thrombin inhibitors may become
      the drug of choice for certain indications.

PMID- 12811008
TI  - Development of argatroban as an anticoagulant and antithrombin agent in Japan.
AB  - Argatroban is a synthetic direct thrombin inhibitor which has been used in Japan
      for three indications, namely, chronic arterial occlusion, acute cerebral
      thrombosis and hemodialysis in AT-deficient patients or in patients with
      decreased AT. In patients with chronic arterial occlusion, argatroban increased
      the skin temperature, reduced the size of skin ulcers, and decreased the thrombin
      antithrombin complex. In patients with acute cerebral thrombosis, neuronal
      symptoms improved significantly compared with the placebo group, wherein
      activated partial thromboplastin time (aPTT) was prolonged by about 1.5-fold and
      fibrinopeptide A was reduced. In some patients in whom hemodialysis is difficult
      due to the generation of blood clots in the dialyzer, hemodialysis is now
      possible with the replacement of heparin by argatroban.

PMID- 12811009
TI  - Current perspective on antithrombin drugs.
AB  - Thrombin is a multifunctional serine protease, which is involved in blood
      coagulation and thrombosis, inflammation and wound repair in tissue injury. Its
      role in the amelioration of inflammatory tissue injury has been investigated.
      Protease-activated cell surface receptors (PARs) when activated by thrombin
      result in the production of proinflammatory mediators. In the kidney, these PARs
      are expressed on the glomerular epithelium and the vascular endothelium. The
      significant impact of thrombin inhibition on the development of crescentic
      glomerular nephritis is discussed.

PMID- 12811010
TI  - Clinical results with direct thrombin inhibitors.
AB  - Direct thrombin inhibitors inactivate thrombin without the need for antithrombin
      and some inactivate not only thrombin but also fibrin-bound thrombin. Hirudin has
      been shown to be more effective than low-dose unfractionated heparin and low
      molecular weight heparin for the prevention of deep vein thrombosis in high-risk
      orthopaedic patients. Major studies are assessing the value of direct thrombin
      inhibitors in patients with acute coronary syndromes. Currently, argatroban is
      the drug of choice in patients with heparin-induced thrombocytopenia.

PMID- 12811011
TI  - Argatroban in thrombotic stroke.
AB  - Evidence for the potential use of direct thrombin inhibition in the treatment of
      acute stroke is reviewed. Reduction of secondary microthrombi and improved
      regional collateral cerebral blood flow is the proposed mechanism of action of
      thrombin inhibition for the treatment of cerebral ischemia. A clinical study in
      Japan found that argatroban administered within 48 h of stroke symptom onset is
      safe and effective in reducing neurological impairment due to ischemic stroke.
      The implications of further clinical studies are discussed.

PMID- 12811012
TI  - Argatroban in HIT type II and acute coronary syndrome.
AB  - Prior to initiation of the ARG-911 and ARG-915 clinical trials, there was no
      optimal replacement for heparin anticoagulation in patients with heparin-induced
      thrombocytopenia (HIT) type II. These prospective, historical controlled studies
      were designed to determine the usefulness of argatroban, a direct thrombin
      inhibitor (DTI) that is not immunogenic and does not interact with heparin
      antibody, in answering this clinical need. Clinical outcomes (37-day period) for
      568 argatroban-treated and 193 control patients demonstrated significantly
      reduced risks of the primary efficacy composite endpoint (all-cause death, all
      cause amputation, new thrombosis) and the secondary endpoints (death due to
      thrombosis, new thrombosis) with argatroban. Argatroban patients also experienced
      a more rapid recovery of platelet count. Bleeding events were similar among both
      groups. It was concluded that argatroban anticoagulation, compared with
      historical controls, improves clinical outcomes without increasing bleeding risk
      in patients having HIT with or without thrombosis. Argatroban has since been
      approved in the US for both prophylaxis and treatment of thrombosis in patients
      with HIT. Argatroban has been used in percutaneous coronary interventions in
      patients with and without HIT, for peripheral vascular procedures in both large
      and small vessels in HIT patients, and as an adjunct to thrombolytic therapy for
      the treatment of AMI. Treatment success rates and the same or less bleeding was
      demonstrated with argatroban compared to heparin controls. These pilot studies
      suggest that argatroban will provide reliable anticoagulation during
      interventional procedures. A consistent safety profile of argatroban has been
      demonstrated in all studies to date. The main attributes of argatroban are its
      rapid onset of action, fast reversibility of its anticoagulant effect, inhibition
      of clot-bound thrombin, easily monitored by the aPTT and ACT and no dosage
      adjustment in renal-impaired individuals. These properties make argatroban a
      predictable and useful anticoagulant for HIT and non-HIT patients.

PMID- 12811013
TI  - Practical issues in the development of argatroban: a perspective.
AB  - Argatroban was the very first antithrombin agent that was approved for clinical
      use. It represents a synthetic arginomimetic drug with multiple pharmacologic
      properties. Unlike other antithrombin drugs, argatroban is a reversible
      antithrombin agent. Furthermore, it modulates endothelial cell function and
      downregulates various inflammatory and thrombotic cytokines. Argatroban is an
      effective anticoagulant agent, which at equivalent anticoagulant levels
      (activated clotting time; ACT) produces a stronger anticoagulant effect in
      comparison to heparins and hirudins. At a comparable ACT (300 s), argatroban
      produces much stronger inhibition of thrombin generation as measured by F(1.2)
      and thrombin-antithrombin complex generation. Argatroban does not generate any
      neutralizing or non-neutralizing antibodies and, therefore, it does not require
      any dosage adjustment during the course of therapy as other thrombin inhibitors
      require. The pharmacological profile of argatroban is unique as this antithrombin
      drug not only inhibits thrombogenesis but also modulates cellular functions.
      Because of its broad spectral actions, argatroban will have more expanded
      indications.

PMID- 12811014
TI  - Molecular mechanisms of dendritic cell sublineage development from human
      hematopoietic progenitor/stem cells.
AB  - In vitro differentiation models of human CD34+ hematopoietic progenitor/stem
      cells have contributed significantly to our current understanding of dendritic
      cell (DC) development. DC sublineages seem to arise from common progenitors with
      monocytic cells. These progenitors seem to respond to instructive signals from
      cytokine receptors and steroids to follow defined sublineage differentiation
      pathways. Transcriptional processes involved in the regulation of lineage fate
      decisions of putative common DC progenitors remain poorly defined, as is our
      knowledge of the identities of DC precursors in vivo. Most likely, tissue
      specific microenvironmental signals, including tumor-derived signals, critically
      modulate DC phenotype and function in vivo.

PMID- 12811015
TI  - Nerve growth factor: neurotrophin or cytokine?
AB  - Nerve growth factor (NGF) is a neutrophin exerting an important role in the
      development and functions of the central and peripheral nervous system. However,
      it has recently been documented that several immune cells - such as mast cells,
      lymphocytes and eosinophils - produce, store and release NGF. Moreover, NGF high
      and low affinity receptors are widely expressed in the immune system, thus
      indicating the potential of responding to this neurotrophin through an autocrine
      mechanism. In fact, NGF influences development differentiation, chemotaxis and
      mediator release of inflammatory cells as well as fibroblast activation through a
      complex network influenced by other pro-inflammatory cytokines. Finally, NGF is
      increased in biological fluids of several allergic, immune and inflammatory
      diseases. Data reviewed suggest, therefore, that NGF might also be viewed as a
      (Th2?) cytokine with a modulatory role in allergic inflammation and tissue
      remodeling.

PMID- 12811016
TI  - Lipid transfer protein 1 is a possible allergen in Arabidopsis thaliana.
AB  - BACKGROUND: The Arabidopsis thaliana genome was recently fully sequenced, and
      this plant is now considered as the most useful model to study the effects of
      genetic engineering. The aim of the present study was to identify A. thaliana IgE
      binding molecules and to localize their genes in order to evaluate the potential
      effect of gene insertion on the expression of IgE-binding molecules. METHODS: A.
      thaliana flower proteins were separated by two-dimensional gel electrophoresis
      and transferred onto a nitrocellulose sheet. The nitrocellulose sheet was
      successively incubated with human sera known to contain IgE that binds to
      rapeseed proteins, alkaline phosphatase-conjugated goat anti-human IgE and 5
      bromo-4-chloro-3-indolyl phosphate and nitroblue tetrazolium. One allergen was
      further identified by N-terminal amino acid microsequencing. RESULTS: The results
      showed that some individuals possessed IgE that recognized numerous proteins with
      high molecular masses and various isoelectric points. This binding pattern
      strongly suggests that the epitopes recognized by these IgE could be, at least
      partly, sugar residues. Otherwise, out of the 10 sera that possessed IgE to
      Arabidopsis flower proteins, one serum strongly recognized a unique basic protein
      with an apparent molecular mass of around 14 kD. This protein was identified by
      amino acid microsequencing as the lipid transfer protein 1 (LTP1). CONCLUSION: We
      have demonstrated that A. Thaliana LTP1 is IgE reactive. The gene encoding this
      protein is located on chromosome 2, but it has been described that family 1 of A.
      Thaliana LTPs constitutes a multigenic family with genes located on various
      chromosomes.

PMID- 12811017
TI  - Molecular cloning and characterization of hazel pollen protein (70 kD) as a
      luminal binding protein (BiP): a novel cross-reactive plant allergen.
AB  - BACKGROUND: Tree pollen contains many allergens showing cross-reactivity to
      proteins from pollen, seeds, and fruits of different plant species. Amongst
      Fagales, responsible for several allergenic responses, hazel provides the best
      material to study pollen as well as food allergens in one species. The aim of
      this study was to identify and characterize the physiological function of an
      allergen from hazel pollen and to determine possible cross-reactivity to proteins
      from hazelnut. METHODS: Monoclonal antibodies (mAbs) against hazel pollen crude
      extract were produced. On the basis of IgE binding, demonstrated by sera from
      patients allergic to hazel pollen, one mAb indicating the best correlation has
      been selected, and the putative allergen was purified by preparative gel
      electrophoresis. Isoforms were investigated by two-dimensional PAGE, and for
      molecular identification a hazel pollen cDNA library was constructed. In situ
      localization of the allergen during pollen development was performed by
      immunofluorescence labelling. RESULTS: Immunological staining of crude hazel
      pollen extract with specific IgE and mAb revealed a 70-kD protein. Immunoblot
      studies with mAb showed cross-reactive proteins of 70-72 kD in different plant
      tissues and species. After protein purification, the IgE-binding reactivity of
      the allergen has been reconfirmed, and two isoforms were detected. Molecular
      cloning identified the allergen as a luminal binding protein (BiP) of the Hsp70
      family with 88-92% sequence identity in various plants. Further immunocytological
      studies indicated involvement of BiP during pollen development. CONCLUSIONS:
      Chaperons like BiP play an important role in protein synthesis and in the
      protection of cellular structures during stress-related processes. Because of
      their highly conserved protein sequences, we propose that such allergens could be
      responsible for at least a part of the allergenic cross-reactivity between
      proteins from different pollens and plant foods.

PMID- 12811018
TI  - Magnoliae flos induces apoptosis of RBL-2H3 cells via mitochondria and caspase.
AB  - BACKGROUND: Magnoliae flores (MF), the buds of Magnolia denudata Desrousseaux,
      have been successfully used for the management of allergic diseases in Korea. The
      purpose of the present study was to determine their causal role in inducing
      apoptosis of mast cells and to verify the underlying mechanism. METHODS: The
      viability of mast cells was assessed by the trypan blue exclusion test. Induction
      of apoptosis was confirmed by DNA fragmentation, nuclear staining and DNA
      hypoploidy. Western blotting and immunofluorescent staining were performed to
      study the alterations in expression level and translocation of apoptosis-related
      proteins. Mitochondrial membrane potential (MMP) change and cytochrome C release
      were assayed. RESULTS: We present several lines of evidence indicating that MF
      induce apoptosis. Changes in cell morphology, generation of DNA fragmentation,
      cell cycle arrest, activation of caspase-3, and PARP and DFF degradations were
      demonstrated. The reduction of MMP and the release of cytochrome C to cytosol
      were also shown. Either PTP blockers, bongkrekic acid and cyclosporin A, or
      pancaspase inhibitors, Boc.D-fmk and zVAD-fmk, did not prevent the release of
      cytochrome C. Bax protein content was increased, and Bax was translocated from
      cytosol into mitochondria at early time points after MF treatment. CONCLUSIONS:
      We have demonstrated that MF induce mitochondria- and caspase-dependent mast cell
      apoptosis. Our observations contribute new insights to the role of MF and support
      the view that the clinical effect of MF may depend on their pharmacological
      efficacy in regulating mast cell apoptosis.

PMID- 12811019
TI  - A double-blind placebo-controlled evaluation of sublingual immunotherapy with a
      standardized ragweed extract in patients with seasonal rhinitis. Evidence for a
      dose-response relationship.
AB  - BACKGROUND: There is a growing consensus on the benefits of sublingual-swallow
      immunotherapy in the treatment of allergic diseases. METHODS: This randomized,
      double-blind placebo-controlled study was undertaken to assess the efficacy and
      safety of sublingual immunotherapy with standardized ragweed pollen extract
      tablets, in patients with an allergic rhinitis. A total of 110 outpatients were
      randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable
      for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a
      28-day progression phase, the patients received a maintenance treatment during
      6.5 months. Efficacy variables included a global assessment of efficacy (patient/
      investigator), symptoms and medication scores as well as the frequency of asthma
      attacks. RESULTS: In the active treatment group, 43 patients completed the study,
      versus 49 on placebo. During the whole period of pollination, the difference
      favoring immunotherapy was highly significant for the global assessment by the
      patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were
      reported more often in the active treatment but mild or moderate, and they abated
      after dose adjustment. A subgroup analysis of those patients receiving the
      highest dose of immunotherapy (3 tablets 3 times a week) showed a highly
      significant response for rhinitis and conjunctivitis total scores by comparison
      to lower dosages. CONCLUSION: This study confirms the efficacy and safety of
      sublingual immunotherapy and strongly suggests a dose-response relationship.

PMID- 12811020
TI  - Correlates of sensitization to Blomia tropicalis and Dermatophagoides
      pteronyssinus in asthma in Barbados.
AB  - BACKGROUND: Sensitivity to the mite Blomia tropicalis is related to asthma in
      tropical climates, but correlates of sensitivity to B. tropicalis and its
      relationship to Dermatophagoides pteronyssinus sensitivity have not been widely
      examined in families with asthma. The main objective of this study was to
      determine prevalence and correlates of sensitivity to these mites in families
      with asthma and characteristics of persons sensitized to both. METHODS:
      Antibodies to major antigens (Blo t 5 and Der p 1) of these mites were measured
      by immunochemiluminescent assay in 481 members of 29 families from Barbados
      ascertained through two asthmatic siblings. RESULTS: Blo t 5 sensitivity was
      present in 261 subjects (46%) and was associated with younger age, higher total
      serum IgE level, and more than a three-fold increased prevalence of asthma (42
      vs. 13%). Der p 1 sensitivity was less common (27%) and showed similar
      associations with age, IgE, and asthma. Of the 261 subjects sensitized to Blo t
      5, 116 were also sensitized to Der p 1; they were younger, had higher total and
      Blo t 5 specific IgE levels, and had more than twice the asthma prevalence as
      those sensitized to Blo t 5 alone (59 vs. 29%). Der p 1 sensitivity without Blo t
      5 sensitivity was uncommon; 90% of those sensitized to Der p 1 were also
      sensitized to Blo t 5. Geometric mean total IgE levels were lowest in the 207
      participants without any mite sensitization (102 U/ml), intermediate in 158
      sensitized to either Blo t 5 OR Der p 1 (609 U/ml), and highest in 116 sensitized
      to both (1,869 U/ml). CONCLUSIONS: Blo t 5 is the predominant sensitizing mite
      allergen in these Barbadian families with correlates similar to Der p 1.
      Concomitant sensitization to Der p 1 appears to identify a more reactive subgroup
      of individuals at a higher risk of asthma.

PMID- 12811021
TI  - Acute effect of air pollution on respiratory complaints, exhaled NO and
      biomarkers in nasal lavages of allergic children during the pollen season.
AB  - During 2 months of the pollen season, the acute and putative adjuvant effect of
      traffic-related air pollution on respiratory health was investigated in children
      sensitised to grass pollen or house dust mite (HDM). Respiratory complaints were
      objectified via measurement of exhaled NO and inflammatory mediators in nasal
      lavage (NAL). During the study children, skin prick negative (n = 31) or positive
      to grass pollen (n = 22), HDM (n = 34) or grass pollen + HDM (n = 32), kept a
      daily diary on respiratory symptoms, and NAL and exhaled air was sampled twice a
      week. The level of air pollutants and pollen was monitored continuously. Like
      children sensitised to HDM, those sensitised to pollen reported respiratory
      complaints (shortness of breath, itchy eyes or blocked nose) more frequently than
      non-sensitised children during (but not before) the pollen season; the
      respiratory complaints of sensitised children were independent of the pollen
      level. In addition, exposure to increased levels of PM(10) induces 'shortness of
      breath' in pollen- and HDM-sensitised children, whereas ozone induces a blocked
      nose in HDM-sensitised children. Combined exposure to PM(10) + pollen and O(3) +
      pollen induces a blocked nose in both HDM-sensitised children and children
      sensitised to pollen + HDM. Significant positive associations were found between
      eNO and the levels of NO(2), CO, PM(2.5) and pollen in both sensitised and non
      sensitised children. At the start of the pollen season, the NAL concentration of
      eosinophils and ECP in pollen-sensitised children was increased compared to
      winter, but their levels were not further affected by increased exposure to
      pollen or air pollution. In conclusion, during the pollen season, sensitised
      children continuously report a high prevalence of respiratory complaints which
      coincides with increased levels of upper and lower airway inflammatory markers.
      No additional pro-inflammatory effect of air pollution was observed, which
      indicates that air pollution does not facilitate allergen-induced inflammatory
      responses.

PMID- 12811022
TI  - Oral allergy syndrome to fig.
AB  - BACKGROUND: The few cases of food allergy to fig reported to date, whose main
      manifestations were anaphylactic reactions, have been related to a cross
      sensitisation to weeping fig (Ficus benjamina) or to the 'latex-fruit syndrome'.
      Here we report on two cases of the oral allergy syndrome (OAS) to fig in patients
      whose main allergic manifestations were related to sensitisation to grass and
      birch pollens. METHODS: The patients were characterised by clinical history, skin
      prick tests (SPT) with commercial and in-house extracts, prick-by-prick test,
      specific IgE measurements and challenge tests. PBS-soluble and insoluble extracts
      of both fig skin and pulp were examined for the presence of potential allergens
      by IgE immunoblotting. RESULTS: Both patients showed OAS followed by respiratory
      symptoms when challenged with fig. They were negative in both specific IgE
      detection and SPT with commercial extracts of fig and many other plant materials,
      including F. benjamina and Hevea Brasiliensis, while grass and birch pollens gave
      positive results. Prick-by-prick tests and SPT with in-house extracts indicated
      that the fig skin had a much higher allergenicity than the pulp. Despite negative
      IgE detection by the CAP assay, immunoblotting experiments showed that potential
      fig allergens were PBS-soluble and present only in the skin of the fruit.
      CONCLUSIONS: OAS to fig followed by respiratory symptoms can be present in
      patients not sensitised to weeping fig or having the latex-fruit syndrome.
      Different parts of the fig can have different allergenicities, the most important
      allergens being proteins related to the skin of the fruit. Improved commercial
      fig extracts to be used for the diagnosis of this type of allergy have to be
      developed.

PMID- 12811024
TI  - Host genetic factors in the clinical course of HIV-1 infection: chemokines and
      chemokine receptors.
AB  - The outcome of HIV-1 infection is highly variable: not all individuals exposed to
      HIV-1 will become infected, and among individuals who do become infected, the
      time from seroconversion to AIDS diagnosis is highly variable. Some patients may
      develop AIDS within 3 years, whereas others may remain asymptomatic for over 15
      years. The reasons for these differences are not fully understood, but are
      thought to reflect the complex interactions between virus and host. In recent
      years, an important role for host genetic factors in the pathogenesis of HIV-1
      infection has increasingly been appreciated. Many novel genetic polymorphisms
      have been identified and analyzed for their role in HIV-1 transmission and
      disease progression. In this review, we will give an update of the current
      knowledge on the role of such polymorphisms in HIV-1 disease. As recent research
      in this field has focussed on polymorphisms in chemokine and chemokine receptor
      genes, this will be the main theme of our review.

PMID- 12811023
TI  - Inhibitory activity of CX-659S, a novel diaminouracil derivative, against the
      rebound phenomenon following withdrawal of corticosteroid therapy for chronic
      contact hypersensitivity responses.
AB  - BACKGROUND: CX-659S, a newly discovered anti-inflammatory compound, exerts
      inhibitory effects on chronic contact hypersensitivity responses (CHRs) induced
      by repeated application with picryl chloride (PC), which is known to mimic many,
      if not all, events occurring within lesional skin of patients with atopic
      dermatitis (AD). CX-659S suppresses the expression of mRNA for interleukin (IL)-4
      and IL-10 but not that for IFN-gamma, and inhibits serum IgE production in a
      chronic CHR model. Although topical corticosteroids have been widely utilized in
      steroid-responsive dermatoses such as AD, their chronic use may be associated
      with significant side effects. In addition, a rebound phenomenon often occurs
      after discontinuation of prolonged use of topical corticosteroids, with enhanced
      production of IgE and Th2 cell cytokines. The purpose of this study was to assess
      whether CX- 659S inhibits the rebound phenomenon after discontinuation of chronic
      treatment with prednisolone in a chronic CHR model in mice. METHODS: The efficacy
      of CX-659S as a sequential therapeutic agent after discontinuation of chronic
      treatment with prednisolone was tested on PC-treated ears of BALB/c mice with
      chronic CHR. Effects were quantified by measurements of ear thickness, serum IgE
      and cytokine mRNA expression. RESULTS: The rebound phenomenon was confirmed after
      discontinuation of chronic treatment with prednisolone in chronic CHR in mice,
      i.e. by evidence of flare thickening of the ear, enhanced expression of mRNA for
      IL-4 and IL-10 and increased serum IgE. Sequentially applied CX-659S suppressed
      these rebound phenomena with a good cosmetic result. CONCLUSIONS: CX-659S is the
      first promising compound with inhibitory activity on the rebound phenomenon
      following withdrawal of corticosteroid therapy without immunosuppression.

PMID- 12811025
TI  - Thalassaemia carrier testing in Pakistani adults: behaviour, knowledge and
      attitudes.
AB  - OBJECTIVES: To describe beta-thalassaemia (thalassaemia) carrier testing
      behaviour (whether tested or intentions of testing) amongst a sample of UK
      Pakistani adults; their level of knowledge about thalassaemia, and their
      attitudes toward thalassaemia carrier testing. METHOD: In a cross-sectional
      design semi-structured interviews, data were obtained from 59 Pakistani adults
      including 19 parents of children with thalassaemia; 20 of their relatives, and 20
      'lay' adults. The outcome measures include: knowledge of thalassaemia and genetic
      inheritance, carrier testing behaviour, attitudes toward carrier testing and
      source of information about thalassaemia. RESULTS: Knowledge about carriers and
      inheritance of thalassaemia was low. Intention to have carrier testing was low in
      those participants who had not been tested. Participants generally had positive
      attitudes toward carrier testing. Relatives and lay adults most frequently
      identified a thalassaemia family member as their source of information about
      thalassaemia, and only seven parents identified 'a health service source' as
      their source of information. CONCLUSION: Pakistani adults have insufficient
      knowledge to be aware of their risk of carrying a gene that may result in the
      birth of a child with thalassaemia. This finding may explain in part why
      intention to have carrier testing was low. Although thalassaemia is discussed in
      families where the disease is present, it is unlikely that information about its
      inheritance is discussed. Further empirical evidence is needed to improve the
      quality of information disseminated by both professionals and non-professionals
      to ensure Pakistani adults are able to make informed decisions about carrier
      testing, prenatal diagnosis and termination of pregnancy.

PMID- 12811026
TI  - Genetics in primary care: a USA faculty development initiative.
AB  - The Genetics in Primary Care (GPC) project is a USA national faculty development
      initiative with the goal of enhancing the training of medical students and
      primary care residents by developing primary care faculty expertise in genetics.
      Educational strategies were developed for the project by an executive committee
      with input from an advisory committee, comprising individuals with primary care,
      medical education and genetics expertise. These committees identified the key
      issues in genetics education for primary care as (1) considering inherited
      disease in the differential diagnosis of common disorders; (2) using appropriate
      counseling strategies for genetic testing and diagnosis, and (3) understanding
      the implications of a genetic diagnosis for family members. The group emphasized
      the importance of a primary care perspective, which suggests that the clinical
      utility of genetic information is greatest when it has the potential to improve
      health outcomes. The group also noted that clinical practice already incorporates
      the use of family history information, providing a basis for discussing the
      application of genetic concepts in primary care. Genetics and primary care
      experts agreed that educational efforts will be most successful if they are
      integrated into existing primary care teaching programs, and use a case-based
      teaching format that incorporates both clinical and social dimensions of genetic
      disorders. Three core clinical skills were identified: (1) interpreting family
      history; (2) recognizing the variable clinical utility of genetic information,
      and (3) acquiring cultural competency. Three areas of potential controversy were
      identified as well: (1) the role of nondirective counseling versus shared
      decision-making in discussions of genetic testing; (2) the intrinsic value of
      genetic information when it does not influence health outcomes, and (3)
      indications for a genetics referral. The project provides an opportunity for
      ongoing discussion about these important issues.

PMID- 12811027
TI  - Changes of anti-Clonorchis sinensis IgG antibody in serum after praziquantel
      treatment in human clonorchiasis.
AB  - Anti-Clonorchis IgG antibody levels in serum were observed by ELISA in 129 egg
      positive cases and in 25 controls. The antibody levels were 0.063 to 1.216
      (0.325+/-0.202)in clonorchiasis cases and 0.078 to 0.670 (0.255+/-0.133) in
      controls. The difference was statistically significant. However, serological
      diagnosis of clonorchiasis was not satisfactory in lightly infected cases because
      of low levels of specific IgG antibody. The antibody levels were well correlated
      with EPG. Changes of the IgG antibody levels were not significant 12-14 days, 4
      weeks and 8-9 weeks after praziquantel treatment. Seven and 13 months after
      treatment, the IgG antibody levels were lowered significantly. The period for
      serologically negative conversion after praziquantel treatment was between 9
      weeks and 7 months in human clonorchiasis.

PMID- 12811028
TI  - Intensity of infection and development of adult Clonorchis sinensis in hamsters.
AB  - In an attempt to determine the susceptibility of inbred golden
      hamsters(Mesocricetus auratus) to the experimental infection with Clonorchis
      sinensis, twenty-five hamsters were divided into 5 groups and administered orally
      5, 10, 20, 30 or 50 metacercariae each. The hamsters were killed on the 45th day
      after infection. The adult flukes were recovered from all hamsters. The overall
      recovery rate for the fluke was 57.9 percent with the range of 48.4 percent to
      92.0 percent. As the number of the metacercariae given increased, a proportionate
      decrease in the recovery rate was found. The prepatent period of the fluke in the
      hamster varied from 16 to 17 days, with the average of 16 days. No significant
      differences in the development of the flukes were observed. Egg production
      expressed by EPG, increased step by step as the time elapsed. However, a tendency
      of decreasing egg laying capacity was observed with the increase of worm burden.
      It is suggested that the hamster is a suitable final host of C. sinensis.

PMID- 12811029
TI  - Intracranial synthesis of specific IgG antibody in cerebrospinal fluid of
      neurocysticercosis patients.
AB  - To determine the source of Cysticercus-specific IgG antibody in cerebro-spinal
      fluid(CSF), paired samples of serum and CSF were collected from confirmed
      neurocysticercosis, other neurologic diseases and normal control. The antibody
      levels in serum and CSF were measured by enzyme-linked immunosorbent assay
      (ELISA). With the measurement of total protein, albumin and IgG concentration in
      serum and CSF, the contribution of IgG in CSF were calculated in transudation,
      exudation and intracranial synthesis using the formula of Tourtellotte and Ma
      (1978). Mean concentrations of total protein, albumin, IgG and proportional IgG
      levels in CSF by transudation, exudation and intracranial synthesis were elevated
      in neurocysticercosis. But only the intracranial synthesis of IgG showed a
      statistically significant correlation with the specific IgG antibody levels in
      CSF. In CSF from lateral ventricle in the 4th ventricular neurocysticercosis, the
      protein concentrations were normal and the specific antibody levels were
      negative. However, in consecutively secured lumbar CSF from the same patients,
      the former were increased and the latter were positive. These results indicated
      that, in neurocysticercosis, the specific IgG antibody in CSF was a local product
      of intracranial synthesis.

PMID- 12811030
TI  - Comparative evaluation of indirect immunofluorescent antibody test with enzyme
      linked immunosorbent assay in serodiagnosis of human neurocysticercosis.
AB  - The applicability of indirect immunofluorescent antibody test (IFAT) was compared
      with enzyme-linked immunosorbent assay (ELISA) in sera from 163 cases of
      confirmed neurocysticercosis, 101 other neurologic and parasitic diseases and 100
      normal controls. As antigen, frozen sections of a Taenia solium metacestode from
      a human brain was used in IFAT and cystic fluid was used in ELISA. For the
      detection of specific IgG antibody, IFAT was equally sensitive (89. 6%) and
      specific (85. l%) as ELISA. The antibody titers by IFAT were correspondingly
      increased with mean absorbance of ELISA. The corresponding rate of positivity in
      the two techniques was 90.8%. Except for the difficulty in detecting antibodies
      in cerebrospinal fluid (CSF), IFAT was concluded to be very useful for the
      serodiagnosis of human neurocysticercosis.

PMID- 12811031
TI  - [Immunization effect on Naegleria fowleri infection in splenectomized mice]
AB  - A pathogenic free-living amoeba, Naegleria fowleri, is a causative protozoan
      parasite of primary amebic meningoencephalitis in human and experimental animals.
      It is known that humoral and cellular immunity contribute as the defence
      mechanism of host against this organism. Recently splenectomy has been argued on
      its effect on host defence mechanisms. The present study was aimed to observe the
      effect of immunization in splenectomized mice. For immunization, 5-10 x 10(5)
      trophozoites of Naegleria fowleri o 359 were intraperitoneally inoculated once a
      week for two weeks to BALB/c mice, and 5-10 x 10(4) of ameba trophozoites were
      intranasally inoculated for infection after splenectomy and/or immunization.
      ELISA technique was applied for the detection of serum IgG antibody levels.
      Experimental animals were divided into 4 groups; I. splenectomized and immunized;
      II. splenectomized only; III. immunized only; IV. not splenectomized nor
      immunized. The results obtained were as follows: Mortality rates of
      splenectomized and immunized mice in group I (38.1 percent) and immurized only in
      group III (25.0 percent) were lower than those of not immunized mice in group
      II(50 percent) and control group, IV (46.4 percent). Survival times of mice in
      group I, II, III and IV were 20.1+/-3.6, l7.3+/-4.5, 20.4+/-7.0 and 19. 6+/-7.6
      days respectively, and there were no significant differences between them. ELISA
      values (absorbance at 492 nm) of group I (1.10+/-0.29) and group III (1.31+/
      0.28) were signficantly higher than that of group IV(0.24+/-0.37) at day 31 of
      infection (p<0.05). Conclusively, it is presumed that humoral immunity against N.
      flowleri may operate as ever, after immunization, even though the mouse was
      splenectomized.

PMID- 12811032
TI  - Clinical and histopathological findings in mice heavily infected with Fibricola
      seoulensis.
AB  - To observe the clinical course and intestinal histopathology in heavy infection
      of Fibricola seoulensis, an experimental study was performed in mice. Clinical,
      hematological and histopathological observation was done on 1, 3, 7 and 12 days
      after experimental infection with l,000 metacercariae. On the 11th day after
      infection, the mice began to die and all of the infected mice were dead by the
      16th day. The infected mice showed gradual weight loss. Occult blood was detected
      after the 10th day. Diarrhea occurred after the 9th day and was recognized in all
      of the infected mice on the 12th day. Hemoglobin and mean corpuscular hemoglobin
      decreased significantly after the 12th day, and mean corpuscular hemoglobin
      concentration decreased in all infected mice. The histopathological changes were
      more marked in the duodenum than in the jejunum or ileum. Major changes were
      villous atrophy and crypt hyperplasia, with decreased villus/crypt ratio,
      inflammatory cell infiltration and stromal edema. The present results suggest
      that the cause of death of mice heavily infected with F. seoulensis should be
      malnutrition and severe fluid loss due to malabsorption, together with intestinal
      bleeding.

PMID- 12811033
TI  - A human case of Centrocestus armatus infection in Korea.
AB  - A human case of Centrocestus armatus (Heterophyidae) infection was proved by
      identifying an adult worm collected after treatment with praziquantel in Korea.
      The case is 42-year old man who resides in a rural area in Sanchung-gun,
      Kyeongsangnam-do. The case was concomitantly infected with Clonorchis sinensis
      and had the history of eating raw freshwater fishes including Zacco platypus,
      which are known to be the second intermediate host of C. armatus in Korea. This
      is the first report of natural human infection by C. armatus in the literature.

PMID- 12811034
TI  - [A case of natural human infection by Echinostoma cinetorchis]
AB  - A human case of Echinostoma cinetorchis infection was found in Seoul Paik
      Hospital on August 1987. Large trematode eggs, 98.9 x 62.7 micro-m in average
      size, were detected in stool examination. The eggs had a small-sized operculum
      and abopercular wrinkling. After treatment with praziquantel(single dose of 16.2
      mg/kg) and purgation with magnesium citrate, an adult fluke was collected. It was
      8.0 mm long, equipped with 37 collar spines around head crown, and had only one
      testis just behind the Mehlis' gland. It was identified as E. cinetorchis Ando et
      Ozaki, 1923. The patient is an 18-year old man residing in Seoul, and was
      hospitalized due to nephritis. He had eaten raw meat juice of fresh water fishes
      such as top minnows(Oryzias latipes) and loaches, or tadpoles, which are
      considered possible souce of this fluke infection. This is the 4th human case of
      E. cinetorchis infection in Korea.

PMID- 12811035
TI  - Identification of Stellantchamus falcatus Metacercariae encysted in mullets in
      Korea.
AB  - A group of metacercariae encysted in the flesh of Mugil sp. were identified to be
      Stellantchasmus falcatus by the morphology of adult worms obtained
      experimentally. It is confirmed that mullets serve as a second intermediate host
      of this heterophyid fluke in Korea.

PMID- 12811036
TI  - Toxoplasmacidal effect of HL-60 cells differentiated by dimethylsulfoxide.
AB  - In vitro culture of Toxoplasma gondii in HL-60 cells cnd cell-mediated immunity
      against Toxoplasma in dimethylsulfoxide(DMSO)-induced HL-60 cells, i.e.,
      differentiation into granulocytes, were pursued. HL-60 cells were treated with
      various concentrations of DMSO, and 1.3%(v/v) for 3 day incubation was chosen as
      the optimal condition for differentiation into granulocytes. The degree of
      differentiation was assayed in physiological and functional aspects in addition
      to morphological point. When treated with 1.3% DMSO for 3 days, HL-60 cells did
      not synthesize DNA materials beyond background level, and showed active
      chemotactic response to chemotactic peptide, formyl-methionyl-leucyl
      phenylalanine(FMLP). Morphologically promyelocytes of high
      nuclear/cytoplasmic(N/C) ratio changed to granulocytes of relatively low N/C
      ratio. The relationships between HL-60 cells or DMSO-induced HL-60 cells and
      Toxoplasma were examined after stain with Giemsa and fluorescent dye (acridine
      orange). HS-60 cells did not show any sign of toxoplasmacidal activity but showed
      intracellular proliferation of Toxoplasma to form rosette for 72 hr co-culture.
      In contrast, DMSO-induced HL-60 cells phagocytosed Toxoplasma within 1 hr, and
      performed a process of intracellular digestion of Toxoplasma thereafter. With the
      above results, it is suggested that phagosome-lysosome fusion is one of the
      critical events for the parasitism by Toxoplasma or for susceptibility of host
      cells. The in vitro culture system of this study has offered a defined condition
      to study the protozoan parasite-host cell interactions.

PMID- 12811037
TI  - Immunoblot observation of antigenic protein fractions in Paragonimus westermani
      reacting with human patients sera.
AB  - In order to observe the antigenic fractions in saline extract of adult
      Paragonimus westermani, proteins in the crude extract were separated by sodium
      dodecyl sulfate-polyacylamide gel electrophoresis (SDS-PAGE) in reducing
      conditions. The separated protein fractions were transferred to nitrocellulose
      paper on which 20 sera from human paragonimiasis were reacted and immunoblotted.
      Out of 15 stained protein bands in SDS-PAGE, 7 reacted with the sera. Of 14
      reacted bands, 30 kilodalton(kDa) band was the most frequently reacted (95%) and
      was a strong antigen. Protein bands of 23 and 46 kDa were also strong antigens.
      Bands of over 150 kDa, 120 kDa, 92 kDa, 86 kDa, 74 kDa, 62 kDa, 51 kDa, 32 kDa,
      28 kDa, 16.5 kDa and 15.5 kDa were also reactive but their frequencies of the
      reaction were variable.

PMID- 12811038
TI  - Imunological characterization of antigens from cysticercus and sparganum and
      their application to immunodiagnosis 1. Immunological characteristics of crude
      antigenic components from Cysticercus cellulosae.
AB  - We studied the serological reaction between various antigenic components from
      Cysticercus cellulosae and IgG antibodies in sera of cysticercosis, sparganosis,
      hydatidosis patients and normal humans by ELISA and EITB. In serological tests by
      ELISA, we recognized cross reaction of Cysticercus antigenic components with IgG
      antibodies in heterologous sera such as sparganosis and hydatidosis patients or
      normal humans. The crude antigenic components of Cysticercus showed lower ELISA
      sensitivity in homologous sera from cysticercosis patients than heterologous sera
      from hydatidosis patients. A total of 31 polypeptide bands with 260 KDa-22 KDa
      molecular weights were detected by SDS-PAGE, and 11 of them showed strong
      intensity. Total 22 components of them were recognized by IgG antibodies in
      cysticercosis patients sera. However, 12 of them were recognized also by normal
      human sera, 11 were by sparganosis sera, and 21 were by hydatidosis patients
      sera. The crude antigenic components of 104 KDa, 82 KDa, 72 KDa, 59 KDa and 34
      KDa molecular weights were nonspecific ones, which cross-reacted with sera of
      either cysticercosis, sparganosis, hydatidosis patients or normal humans.

PMID- 12811039
TI  - [Studies on the current epidemiological situation of brugian filariasis in
      endemic areas of Korea]
AB  - An epidemiological study on brugian filariasis was carried out in endemic areas
      including Cheju Island in Korea, with a brief review of literatures.The results
      showed that the incidence among residents has remarkably decreased in Cheju
      Island, which was the main endemic area. Reviewing available informations on the
      prevalence of filariasis reported in recent years and also judging from the
      present socio-economic conditions which enable people to practice personal
      protection against mosquitos, it can be said with confidence that filariasis has
      almost disappeared from Cheju Island and inland areas. The disease is considered
      to remain at a low level of endemicity in Hugsan Islands. Certainly mass
      diethylcarbamazine (DEC) treatment carried out in Cheju Island in the 1960s and
      1970s and remarkable economic growth followed by improved living standard and
      altered life-style of inhabitants could all have combined effects on the
      disappearance of this mosquito-borne diseae in this island. If the present trends
      go on, the possibility of resurgence of filariasis in Cheju Island is hardly
      postulated.

PMID- 12811040
TI  - Changing patterns of infection with digenetic larval trematodes from fresh-water
      fish in river Taewha, Kyongnam province.
AB  - Recent patterns of infection with digenetic larval trematodes in fresh-water and
      brackish-water fish were studied in three locations of the river Taewha during
      the period from April to October 1988, and compared with the data reported
      previously in the same river. Of 16 species of fish examined, the encysted larvae
      of Cyathocotyle orientalis were found most frequently from 9 species of fresh
      water fish. The metacercariae of Echinochasmus sp., Metacercaria hasegawai and
      Metagonimus yokogawai were found 8 species, those of Clonorchis sinensis from 7
      species, and Exorchis oviformis and Metorchis orientalis from 5 species of fish.
      The infection rates of fish with C. sinensis metacercariae were not lower than
      those reported in 1980, wheres their intensity of infection was found lowered in
      3 species, Coreobagrus brevicorpus, Gnathopogon atromaculatus, and Puntungia
      herzi. The infection rates of 3 species of fish with M. yokogawai metacercariae
      were lower than the results in 1982, while the rate was higher in 2 species,
      Zacco platypus, and Z. temmincki, and rather stationary in Plecoglossus
      altivelis. The intensity of infection in several species of fish appeared rather
      higher than in 1980. the encysted larvae of C. orientalis, Echinochasmus sp., E.
      oviformis and Metacercaria hasegawai showed variations in infection rates of fish
      in 1980 and in the present study. It was found that the rate of infection with
      digenetic larval trematodes in fresh-water fish was still relatively high in the
      river Taewha, and the metacercarial burden in the fish varied greatly by
      different fish in 1980 and in the present study.

PMID- 12811041
TI  - Status of intestinal parasitic infections in a remote island, Yondo, Jeonranam
      do: province.
AB  - This study was performed to observe the present status of intestinal parasitic
      infections in a remote island, Yondo, located in southern part of Jeonranam
      do(province), Korea. In February and May 1988, total 1,011 individual stool
      samples were collected and examined for intestinal helminths and protozoa using
      formalin-ether centrifugal sedimentation technique. The results are summarized as
      follows: Of 1,011 ingabitants examined, 398(39.4%) were positive for intestinal
      parasites. Helminth positives were 372(36.8%), and protozoan cyst positives were
      56(5.5%). Ten species of parasites were found. Trichuris trichiura revealed the
      highest infection rate of 27.5%, Ascaris lumbricoides 17.4%, Taenia sp. 5.8%,
      Entamoeba coli 3.3%, Giardia lamblia 1.5%, Endolimax nana 0.8%, Hymenolepis nana
      0.4%, hookworm 0.2%, Trichostrongylus orientalis 0.2%, and Entamoeba histolytica
      0.2%, respectively. The female group showed higher positive rate (44.0%) than
      males (34.7%). Also, higher positive rates were observed among adults as compared
      with the group younger than 10 years old. Average value of E.P.G. was 1,876(range
      200-17,800) in A. lumbricoides positives, and 327(range 200-1,600) in T.
      trichiura positive cases. In helminth egg positive cases, single infection was
      63.4%, double infection 34.7%, and triple infection 1.9%, respectively. Among
      protozoan cyst positives, single infection was 94.6%, and double infection was
      5.4%. The present study revealed that the prevalence of intestinal parasites
      among inhabitants in Yondo island is still so high that special control measures
      should be performed.

PMID- 12811042
TI  - Membrane proteins and their antigenicity of Toxoplasma gondii.
AB  - Surface membrane proteins of virulent RH strain and tissue cyst-forming Fukaya
      strain of Toxoplasma gondii were analyzed by SDS-polyacrylamide gel
      electrophoresis after LPO-catalyzed surface iodination and lectin blotting, then
      identified the zoite-specific antigens. Prior to the analyses, purification of RH
      tachyzoites from mouse peritoneal exudate and of Fukaya bradyzoites from mouse
      brain tissues were performed by centrifugation on the discontinuous Percoll
      density-gradient. Tachyzoites were obtained at the interface of 50 per cent and
      60 per cent Percoll solution and brain cysts were harvested at the interfaces of
      40-50 per cent and 50-60 per cent, then bradyzoites were obtained by treating the
      cysts with hypertonic solution. The LPO-catalyzed iodination detected 15 KDa and
      14 KDa proteins of bradyzoites and 30 KDa protein of tachyzoites as major bands
      with several other minor bands. But Con A blotting revealed some bands of 200 K
      50 KDa glycoproteins of bradyzoites and 52 KDa band as major and minor bands of
      33 K-20 KDa of tachyzoites. Phytohemagglutinin did not detect any band in the two
      forms. EITB with anti-Fukaya antibody and anti-RH antibody revealed cross
      reactivities between the two forms. Despite the cross-reactivity, anti-Fukaya
      antibody reacted with 15 KDa band of bradyzoites specifically and, anti-RH
      antibody with 52 KDa, 30 KDa, and 25 KDa bands of tachyzoites, respectively. It
      was identified that 15 KDa protein in bradyzoite, which was not a glycoprotein,
      was a major membrane protein with sufficient antigenicity, and in the case of
      tachyzoite, 52 KDa surface glycoprotein (gp52) with specific antigenicity might
      be added to the major surface protein, p30.

PMID- 12811043
TI  - Antigenic protein fractions reacting with sera of sparganosis patients.
AB  - To observe the antigenic protein fractions in saline extract of Spirometra
      mansoni plerocercoid (sparganum), the crude extract was separated in reducing
      conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). The proteins, transferred by electrophoresis to nitrocellulose paper, were
      reacted with sera from 15 surgically confirmed sparganosis and 24 cysticercosis
      patients for immunoblotting. Out of 30 identified protein bands in the extract,
      bands of 29 and 36 kilodaltons (kDa) were the strongest and the most frequently
      reacting with specific antibody (IgG) in sparganosis sera. Bands of higher
      molecular weight also reacted with the sera but their frequency of reactions was
      lower. Sera of cysticercosis reacted with different protein bands in saline
      extract of sparganum, but the cross reactions were observed in strong antigenic
      bands of 29 and 36 kDa.

PMID- 12811044
TI  - [Passive immunity by splenocyte transfer against amebic meningoencephalitis in
      mice]
AB  - The role of passive cell-mediated transfer of immunity against primary amoebic
      meningoencephalitis(PAME) in mice was studied. Naegleria fowleri, ITMAP 359, were
      cultured in CGVS medium. The ICR mice used were six week-old males of average
      weight of 15 g. Immunization was done by three intraperitoneal injections of l x
      10(6) N. fowleri trophozoites at the interval of one week. Splenocytes were
      obtained from normal and immune mice spleens, and 1 x 10(7) cells were
      administered intraperitoneally into mice 3 days before challenge infection. Mice
      were infected intranasally with 7 x 10(4) N. fowleri trophozoites in a 3
      microliter suspension under secobarbiturate anesthesia. Transplants of normal or
      immune splenocytes seem to alter the pattern of the PAME development. The
      splenocytes transferred from immune mice reduced the mortality rate in the N.
      fowleri infected mice, as compared with the mice transferred with the same number
      of normal splenocytes or without splenocyte. The blastogenic response of the
      splenocytes to both lipopolysaccharide and concanavalin A was elevated on day 7
      after infection the mice transinoculated with immune splenocytes. The serum
      antibody titers in the mice transferred with immune splenocytes were increased
      gradually from day 7 up to day 20 after infections by mean of ELISA. It is
      suggested that the transfer of splenocytes from immunized mice conferred immunity
      against N. fowleri infection.

PMID- 12811045
TI  - The wormicidal substances of fresh water fishes on Clonorchis sinensis VII. The
      effect of linoleic acid and ethyl linoleate on parasite viability.
AB  - In an attempt to analyze the clonorchicidal activity of linoleic acid and ethyl
      linoleate in vitro, the wormicidal effects on Clonorchis sinensis were
      chronologically monitored in dose titration experiments. Excysted metacercariae
      were killed within a period of 31.0+/-4.0 min, 149.3+/-4.l min and 207.0+/-13.5
      min with 100.0 mg, 0.1 mg and 0.001 mg linoleic acid, respectively. The time
      required for the linoleic acid to kill adult worms was 167.0+/-0.8 min with 100.0
      mg, 253.0+/-0.8 min with 0.1 mg, and 277.0+/-0.8 min at 0.001 mg titration.
      Clonorchicidal activity of ethyl linoleate was relatively delayed as death was
      observed within 263.3+/-2.9 min, 286.0+/-0.5 min, and 318.0+/-0.8 min for 100.0
      mg/ml, 0.1 mg/ml and 0.001 mg/ml concentrations, respectively. The wormicidal
      effects observed with these pure anticlonorchal substances were found to be
      similar to the biological activity of native products derived from the mucus of
      the fresh water fish.

PMID- 12811046
TI  - The life cycle and larval development of Fibricola seoulensis (Trematoda:
      Diplostomatidae).
AB  - The life cycle of Fibricola seoulensis was studied in the laboratory and in the
      field, with special interests in the larval developments within the eggs and in
      the intermediate hosts. The first emergence of miracidia after incubation of eggs
      in 26C water began on the ninth day. The miracidia, elongate and cylindrical
      shape, had epidermal plates in the formula of 6, 9, 4 and 3, with two pairs of
      flame cells and lateral processes. A kind of fresh water snail, Hippeutis (H.)
      cantori, was found to shed furcocercous cercariae from the 13th day after
      experimental challenge with miracidia while Physa acuta failed to shed. The same
      kind of snail collected from the field also shed the same cercariae. The
      cercariae were equipped with 2 pairs of penetration glands and 5 pairs of flame
      cells. The tadpoles of Rana nigromaculata were found susceptible to experimental
      infection with the cercariae. The same kind of tadpoles collected from various
      areas were also found naturally infected. The metacercariae in the tadpoles which
      were infected experimentally became infective to the definitive host in 21 days.
      The metacercariae were located free in the body cavity of tadpoles, and attained
      sexual maturity in rats in 7 days. The present study successfully followed the
      complete life cycle of F. seoulenis and found that it is possible to maintain the
      life cycle in the laboratory.

PMID- 12811047
TI  - Metacercariae of Echinostoma cinetorchis encysted in the fresh water snail,
      Hippeutis(Helicorbis) cantori, and their development in rats and mice.
AB  - The fresh water snail, Hippeutis(Helicorbis) cantori, caught from the rice
      paddies in Namyangju-gun, Gyeonggi-do, was found to be a new second intermediate
      host of E. cinetorchis in Korea. The metacercariae were found from 89(76.7 %) out
      of 116 snails examined and the average metacercarial burden was 4.7 per infected
      snails. Some developmental characteristics of E. cinetorchis were observed after
      experimental infection of the metacercariae to rats and mice.

PMID- 12811048
TI  - [An epidemiological suryey of Echinostoma hortense infection in Chongsong-gun,
      Kyongbuk province]
AB  - An epidemiological study was performed to know the infection status of E.
      hortense among the human residents and fish intermediate hosts in Chongsong-gun,
      Kyongsangbuk-do. Out of 263 people examined, 59(22.4 per cent) were positive for
      the eggs of E. hortense. Total 152 fresh water tishes (9 species) were examined,
      and Odontobutis obscura interrupta, Misgurnus angullicaudatus and Squalidus
      coreanus were found to harbour the metacercariae of E. hortense. Juvenile or
      adult E. hortense were expelled from 35 out of 54 cases treated with
      praziquantel. The number of worms per individual ranged from l to 649, with the
      average burden of 51. The eosinophil count of infected persons ranged 1-24 per
      cent (6 per cent in average). The number of eggs per day per worm (EPDPW) in
      human host was estimated about 1,478. The results showed that Chongsong-gun is an
      endemic area of E. hortense.

PMID- 12811049
TI  - [Epidemiological studies on Metagonimus infection along the Hongcheon river,
      Kangwon province]
AB  - The Hongcheon river system flows down through the Hongcheon area of Kangwon-do,
      and reaches to the Cheongpyeong Dam in Kyonggi-do. Stool specimens from the
      inhabitants residing along the Hongcheon river basin were examined to detect
      infection rate of Metagonimus sp., and the intermediate hosts were collected to
      detect larval stages. The results obtained were as follows: Thirty-nine (33 males
      and 6 females) out of 529 (314 males and 215 females) inhabitants were infected
      with Metagonimus sp., showing a total positive rate of 7.4 per cent. In eight
      areas surveyed, the specimens from Kulji-ri of Bukbang-myon at the middle part of
      the river showed the highest positive rate of 26.9 per cent (14 positives out of
      52) (males; 38.2 per cent). The specimens from Mogog-ri of Seo-myon at the
      downstream of the river showed a positive rate of 10.4 per cent (13 positives out
      of 125) (males;12.6 per cent). The positive rates in other regions were less than
      10 per cent. The density of the first intermediate host, Semisulcospira sp., was
      the highest in Kulji-ri of Bukbang-myon (10-20 snails per m(2)), and the
      infection rate of Metagonimus cercariae in the snails was 10.7 per cent(13
      positives out of 121 snails). The infection rate of Metagonimus metacercariae in
      Zacco platypus, the fresh water fish favorably eaten raw by the inhabitants, was
      68.2 per cent (30 positives out of 44 fishes), and most metacercariae were
      detected under the scales (89.9 per cent). Adult flukes were obtained from the
      small intestine of a rat, 15 days after infection with the metacercariae obtained
      from Z. platypus. These adult flukes were identified to be the same srecies as
      those obtained from human hosts. By this survey, new endemic areas of Metagonimus
      infection were discovered along the Hongcheon river basin and the main source of
      infection was the fresh water fish, Z. platypus.

PMID- 12811050
TI  - [Recent patterns of Enterobius vermicularis infection in some school children,
      Korea]
AB  - To investigate the infection status of Enterobius vermicularis the author tried
      surveys by scotch-tape anal swap on school-children and household environmental
      factors considered to have influences on the infection were analyzed by an
      inquiry method with questionnaire. The survey was carried out in October 1986 and
      1988 in urban and suburban areas and the results could summarized as follow: The
      egg positive rate in anal swab was 16.0 per cent (male 14.5 per cent, female 17.6
      per cent) out of 2,156 school-children and higher in female group. The egg
      positive rate in suburban school-children (17.5 per cent out of 1,305 children of
      two primary school)was a little higher than that of urban school-children(13.6
      per cent out of 851 children of one primary schools). The questionnaire analysis
      on environmental factors showed some significant relations between the egg
      positive rate and such factors as the number of brothers and sisters,
      householder's occupation, and avalibility of childroom or bathroom. The result
      indicate that, although enterobiasis in school-children has shown decreasing
      tendency in Korea, it is still considerably high in some urban and suburban
      areas.

PMID- 12811051
TI  - [A case of strongloidiasis with hyperinfection syndrome]
AB  - A 73-year-old Korean male was admitted to Jeil hospital with clinical complaints
      of backache, cough, sputum, vomiting and diarrhea. He had a history of long term
      administration of prednisolone. At admission he was comatose and showed
      generalized pitting edema and anasarca. Laboratory data revealed leukocytosis,
      hyperproteinemia with hypoalbuminemia, sepsis, anemia and brown-colored urine.
      Stool examination revealed rhabditiform nematode larvae. By fecal cultivation,
      filariform larvae of Strogyloides were obtained and the patient was diagnosed as
      hyperinfection syndrome due to S. stercoralis infection. On the 3rd day of
      hospitalization, albendazole treatment was started and continued for 4 days. On
      the 7th dsy of hospitalization, sputum revealed filariform larvae. Total 619
      parasitic adult females, expelled by chemotherapy, were collected from the
      diarrheal stool. However, the patient was discharged hopelessly and died at home.

PMID- 12811052
TI  - [Studies on the immunodiagnosis of rabbit clonorchiasis II. Immunoaffinity
      purification of whole worm antigen and characterization of egg, metacercaria and
      adult antigens of Clonorchis sinensis]
AB  - The sensitivity and specificity of crude and affinity-purified antigens of
      Clonorchis sinensis obtained from the infected rabbits were studied. Stage
      specific antigenic proteins from the eggs, metacercariae and adult worms were
      characterized by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme
      linked immunosorbent assay (ELISA) The results were as follows: The antibody
      binding antigen (ABA) purified from whole worm crude antigen (WWA) by CNBr
      activated Sepharose 4B affinity chromatography made 4 specific bands against
      rabbit anti-sera on Ouchterlony gel diffusion plate, while WWA made 7 bands.
      Major WWA protein bands by SDS-PAGE were found at 16,300-18,500 and 28,000-29,000
      daltons, while major ABA protein bands were at 18,000-21,000 and 29,000-31,000
      daltons. The reactivity of ABA with rabbit anti-sera in ELISA was remarkably less
      sensitive than that of WWA. Molecular weights of egg antigen (EGA), metacercarial
      antigen (MEA) and adult worm antigen (WWA) of C. sinensis ranged from 15,000
      200,000 daltons, 15,000-100,000 daltons and 11,000-80,000 daltons, respectively.
      Major WWA proteins consisted mainly of polypeptide bands of low molecular weight,
      less than 31,000 daltons, while those of EGA and MEA consisted of higher
      molecular weights than 30,000 daltons. The ELISA reactivities of WWA to rabbit
      anti-sera were remarkably greater than those of MEA. EGA showed negative reaction
      throughout the experiments. WWA showed higher optical density (O.D.) than 1.0,
      when reacted with rabbit anti-sera obtained at 4-6 weeks after the infection. In
      the rabbit anti-sera later than 12 weeks after the infection, the O.D. reacting
      with WWA showed a plateau without variation. MEA showed relatively low O.D.
      values (<0.6), when reacted with anti-sera from lightly infected groups
      throughout the experiments, although there were some weak positive cases
      (O.D.>0.6) in heavily infected groups. MEA reacted with rabbit anti-sera showed
      negative results on Ouchterlony gel diffusion plates. Summarizing the above
      results, it is suggested that the whole worm antigen prepared from the adult
      worms of C. sinensis is most highly antigenic. However, this antigen might reveal
      cross reactions with other trematodes such as Paragonimus westermani, therefore,
      purification of antigenic proteins from the crude antigen is essential to
      increase the sensitivity and specificity for the immunodiagnosis of
      clonorchiasis.

PMID- 12811053
TI  - Biochemical properties of a purified protein in cystic fluid of Taenia solium
      metacestodes.
AB  - By affinity chromatography using a monoclonal antibody as ligand, Kim et al.
      (1986) purified a protein fraction in cystic fluid of Taenia solium metacestodes
      (CF). In this study, the biochemical properties of the purified protein were
      characterized. Discontinuous-polyacrylamide gel electrophoresis (disc-PAGE) of
      the protein at 4.5~10% separating gel concentration showed its molecular weight
      (MW) to be 150 kilodalton(kDa) in non-denatured state, while denaturing sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that it
      was composed of 3 different subunits with respective MW of 15, 10 and 7 kDa.
      Subunit of 7 kDa was shown to be linked to other subunits by disulfide bonds.
      Isoelectric point of the protein was pH 6.8. The protein was relatively heat
      stable for immunologic analysis. These properties indicated that the protein,
      comprising about 70% of total content in CF, had similar biochemical characters
      with antigen B of Oriol et al.(1971) in hydatid cyst fluid (HF)

PMID- 12811054
TI  - [A comparative study on hydrolase activities in Acanthamoeba culbertsoni and A.
      royreba]
AB  - Specific or non-specific cytolytic processes of free-living amoebae causing
      meningoencephalitis have been emphasized and the cytolytic ability related to
      hydrolases in Entamoeba sp. and Naegleria sp. has also been reported since the
      latter half of 1970's. However, no information on hydrolase activities in
      Acanthamoeba sp. is available. Hydrolases in Acanthamoeba culbertsoni, a
      pathogenic species of free-living amoebae, were assayed and compared with those
      in a non-pathogenic species, A. royreba. Pathogenicity of these two species was
      confirmed through experimental infection to BALB/c mice. Hydrolase activities and
      cytotoxic effects between pathogenic and non-pathogenic species were compared in
      the trophozoites cultured in CGV media and in CHO cell line, respectively. The
      results are summarized as follows: The mice infected with A. culbertsoni were all
      dead 15 days after nasal inoculation, and the mean survival time was 8.5 days.
      Also the mice infected with this pathogenic species mani fested typical
      meningoencephalitis, whereas the mice infected with A. royreba did not.
      Hydrolases detected both in the cell extracts and culture media were acid
      phosphatase, beta-N-acetyl galactosaminidase, beta-N-acetyl glucosaminidase,
      alpha-mannosidase, neutral proteinase and acid proteinase, all of which were
      detected with remarkably higher rate in A.culbertsoni than in A. royreba. A.
      culbertsoni revealed strong cytotoxicity for the target CHO cells, whereas A.
      royreba did not show any specific cytotoxicity. About 80% of the target cells
      mixed with A. culbertsoni were dead 48 hours after cultivation, and more than 95%
      of the target cells were dead 72 hours after cultivation. Hydrolase activities in
      A. culbertsoni cultured with the target cell line were assayed according to the
      culture time. The activities of acid phosphatase, beta-N-acetyl glucosaminidase,
      beta-N-acetyl glucosaminidase, alpha-mannosidase and acid proteinase in this
      pathogenic amoeba were detected higher in amoeba extracts than in culture media
      up to 120 hours after cultivation, but after 120 hours of cultivation those
      activities were detected higher in culture media than in the amoeba lysates.
      Neutral proteinase activity in A. culbertsoni increased more in EBSS medium than
      in the lysate specimens although the activity in the extracts was generally
      steady according to the cultivation time. Summarizing the above results, it is
      concluded that there were differences in hydrolase activities between pathogenic
      A. culbertsoni and non-pathogenic A. royreba, and that some hydrolase activities
      were detected remarkably higher in A. culbertsoni which revealed strong
      cytotoxicity to the target CHO cell line.

PMID- 12811055
TI  - [The karyotype of Fischoederius cobboldi(Poirier, 1883) from Korean cattle]
AB  - As a series of systematic classification of paramphistomes, the worms in the
      rumen and reticulum of 310 Korean cattle slaughtered at Chonju abattoir were
      collected from February 1986 to June 1987 and were classified by morphology of
      the worms. Afterwards, the karyotype of Fischoederius cobboldi (Poirier, 1883),
      which is a very rare species in Korean cattle, was studied with germ cells of the
      worm by means of modified air-drying method. The chromosome numbers in the
      haploid and diploid cells of 315 F. cobboldi were n=9 and 2n=18, respectively.
      The meiotic divisions were observed frequently; 1,904 haploid and 49 diploid
      cells were recognized. Nine pairs of mitotic chromosomes were homologous in the
      metaphase stage and the chromosomes were composed of seven medium-sized
      metacentrics (m) or submetacentrics (sm) and two small-sized submetacentrics
      (sm). While, meiotic metaphases were composed of seven medium and two small-sized
      chromosomes. The 3rd, 4th, 2nd and 5th pairs of chromosomes was metacentric
      having centromere indices of 40.4 per cent, 40.0 percent, 39.7 percent and 38.9
      per cent, respectively, and the remaining ones were submetacentric with
      centromere indices from 32.4 per cent to 36.2 percent. As a series of C-banding
      method, C-band was shown in centromeric region from all of the haploid germ
      cells, except chromosome No. l which included heterochromatin at the tip region.
      Chromosomes No. 4, 6 and 8 showed remarkable C-band distinguished from others.

PMID- 12811056
TI  - [Cercarial chaetotaxy of Clonorchis sinensis]
AB  - The pattern of sensory papillae, chaetotaxy, of the cercaria of Clonorchis
      sinensis was observed. The chaetotaxy was as follows; 5-6 Ci l, 4-5 Ci 2, 5-6 Ci
      3 at lst row, 4 Cii 1, 2 Cii 2, 4 Cii 3, 5-6 Cii 4 at 2nd row, 3-4 Ciii 1, 2-3
      Ciii 2 at 3rd row, and 2 Civ 1, 2-3 Civ 2, 2-3 Civ 3, at 4th row, in cephalic
      region; 2 AiV, l AiD, 2 AiiV, 1 AiiD, 2 AiiiV, 2 AiiiD, 1 AivV, 1 AivD, 1 PiiD, l
      PiiiD, in ventral(V) and dorsal(D) portions of body. Caudal region revealed 2-2-2
      2 formula.

PMID- 12811057
TI  - Egg laying capacity of Fibricola seoulensis in mice and rats.
AB  - The egg laying capacity of Fibricola seoulensis was observed in mice and rats. In
      mice, the mean number of eggs produced by an adult worm a day was 116 at the
      first week after infection, 123 at the 2nd week and 42 at the 3rd week.
      Thereafter, the capacity of about 20 eggs/worm/day was maintained up to one year
      period. In rats, it generally produced more eggs; 49 at 1 week, 250 at 2 weeks,
      216 at 4 weeks, 327 at 6 months and 11 at one year after infection. It survived
      longer than a year in mice and rats.

PMID- 12811058
TI  - Efficacy of praziquantel (Cesocide injection) in treatment of cestode infections
      in domestic and laboratory animals.
AB  - Efficacy of praziquantel (Cesocide injection) by intramuscular (I.M.) route
      against cestode infections was evaluated. Total 93 domestic or laboratory animals
      such as dogs, cats, rats, mice, goats, deers and chickens were used. Animals were
      infected with Dipylidium caninum, Spirometra sp., Taenia pisiformis, Taenia
      taeniaeformis, Hymenolepis nana, Moniezia expansa, Moniezia sp. or Raillietina
      sp. A single dose of praziquantel, 6 mg/kg of body weight, was highly effective
      (97.9%) against cestodes of various kinds disregarding the host species or their
      intensity of infection. At high dose above 6 mg/kg, the cure rate was 100%. All
      the cestodes treated were expelled from the host within 48 hours. The discharged
      proglottids were damaged severely except Hymenolepis nana and Moniezia expansa.
      Intramuscular injection of this drug evoked a brief pain response in a dog, but
      no other side reactions were observed.

PMID- 12811059
TI  - Stictodora sp. (Trematoda: Heterophyidae) recovered from a man in Korea.
AB  - Two adult specimens of heterophyid fluke, which belong to the genus Stictodora,
      were collected from the stool of a 24-year old man after chemotherapy. The flukes
      were morphologically characterized by their small body size (0.90~0.98 mm long
      and 0.38 mm wide) and peculiar structure of ventrogenital sac with armed gonotyl
      (with about 12~15 spines) not enveloping genital pore. Species identification is
      deferred until more worms are obtained, although they closely resemble Stictodora
      fuscatum (Onji and Nishio, 1916). The patient used to eat raw flesh of mullets
      and gobies, which are regarded as the infection source of Stictodora sp.,
      together with 3 other kinds of heterophyids described elsewhere. This is the
      first record of human Stictodora infection in the literature.

PMID- 12811060
TI  - [A case of human thelaziasis occurred in both eyes]
AB  - On October 26, 1987, the authors encountered a case of human thelaziasis
      involving both eyes. The case in Chollapuk-do, Korea, a farmer aged 23,
      complained of mild lacrimation for 3 weeks followed by 1 week duration of foreign
      body sensation in both eyes prior to examination of eyes. The conjunctivae of
      both eyes appeared slightly reddened. No other abnormalities were noticed. Total
      6 worms, one male and two females from each eye, were removed, parasitologically
      studied, and identified as Thelazia callipaeda Railliet and Henry, 1910.

PMID- 12811061
TI  - A human case of Thelazia callipaeda infection with reference to its internal
      structures.
AB  - Female and male nematodes isolated from an eye of a 36 year old Korean man in
      August 1987 were identified as Thelazia callipaeda. This is the 17th record of
      human thelaziasis in Korea. The internal structure of both female and male were
      described.

PMID- 12811063
TI  - Towards a Canadian model of integrated healthcare.

PMID- 12811064
TI  - From the bottom up and other lessons from down under.

PMID- 12811065
TI  - Formal and informal systems of primary healthcare in an integrated system:
      evidence from the United Kingdom.

PMID- 12811066
TI  - Horizontal and vertical healthcare integration: lessons learned from the United
      States.
AB  - Leatt, Pink and Guerriere provide a very rational argument for moving the
      Canadian healthcare system towards a more integrated model. They suggest that the
      current system in Canada is a hodge-podge of disconnected parts. The current
      system is viewed as providing uncoordinated care, with inadequate use of non
      medical practitioners, perverse payment incentives for providers, too much focus
      on treatment of disease, unacceptable wait times for services and related other
      problems. The authors provide extensive documentation of vital components of a
      system they envision for Canada, the rationale for adopting an integrated system
      of services, and conclude by suggesting strategies for achieving integrated
      healthcare. Change towards the new system would concentrate initially on primary
      care, using virtual coordination networks at the local level. Innovative needs
      based funding methods would ensure that individuals throughout Canada receive
      necessary services for keeping them healthy.

PMID- 12811067
TI  - Integrated delivery systems now or...??

PMID- 12811068
TI  - Integrated health organizations in Canada: developing the ideal model.

PMID- 12811069
TI  - The Capital Health Region's early experiences: moving towards integrated
      healthcare.

PMID- 12811073
TI  - Complementary and alternative medicine: how do we know if it works?
AB  - Using a sociological viewpoint, this paper examines the range of definitions for
      complementary and alternative medicine (CAM) and discusses the evidence base for
      its efficacy and safety. The question of what constitutes evidence is considered
      from various perspectives: biomedical, CAM, consumers and practitioners. The
      authors conclude that all these perspectives are required in order to fully
      understand the appeal of CAM in Canadian society's search for appropriate
      healthcare. Most important, the complexity of methods for assessing the evidence
      about CAM is addressed. An inclusive approach is urged that goes well beyond
      randomized clinical trials. Policy recommendations are made in three areas:
      research, regulation and funding.

PMID- 12811070
TI  - A healthy community through health system partnerships: the approach of Markham
      Stouffville Hospital.
AB  - The structure of the Canadian healthcare system, particularly in Ontario, has
      remained remarkably stable over the past 25 years. No other private sector
      industry employing hundreds of thousands of people, spending tens of billions of
      dollars annually and serving millions of consumers every day has survived for 30
      years without the need to reinvent itself in quite fundamental ways. How then has
      the healthcare sector in Canada avoided the pressure to "reinvent itself?"

PMID- 12811074
TI  - Complementary and alternative medicine: socially constructed or evidence-based?
AB  - In their lead paper, Kelner and Wellman set out policy recommendations for the
      development of complementary and alternative medicine (CAM). This commentary
      examines some of the issues raised by Kelner and Wellman that relate to
      regulation of the professions and the nature of evidence. The extent to which the
      development of medicine is evidence-based or socially constructed is questioned.

PMID- 12811075
TI  - The politics of evidence and the evidence for CAM.
AB  - This commentary takes up issues from the lead paper by reference to the situation
      in Australia and New Zealand. It briefly canvasses issues of nomenclature,
      increasing utilization, the postmodern thesis, the nature of evidence and the
      impact of the social movement toward evidence-based medicine and broader
      questions of legitimacy. The author argues that, sociologically speaking, while
      evidence of effectiveness is increasingly important, it will never be the whole
      story of where complementary and alternative medicine fits into the health
      services of the nation.

PMID- 12811076
TI  - Complementary and alternative medicine in Canada: what is the future?
AB  - Complementary and alternative medicine (CAM(is on the rise in both numbers of
      patients and dollars expended. The existence of systems of traditional medicine
      is not new in North America or other parts of the world, but the CAM label has
      been applied to both traditional medicine and newer practices. Traditional
      medicine is uniquely defined by its philosophy and integrative approach and may
      be critically evaluated by different levels of research. Several of the larger
      and more established CAM disciplines meet the criteria of both a traditional
      system of medicine and that of professionalism. There is a need for governments
      to protect the public as CAM practices appear to proliferate, and to move forward
      by regulating those groups that meet the provincial criteria for self-regulation.

PMID- 12811077
TI  - Complementary and alternative medicine: an integrated approach required.
AB  - Methods of verification of the efficacy and safety of health interventions must
      be congruent with the underlying health beliefs. It is therefore inappropriate to
      require scientific validation of health interventions that are not based on
      science. On the other hand, there is no justification for different standards of
      validation of health products from alternative sources that are used by the
      public in a manner similar to prescription and over-the-counter drugs. Public
      monies for health research should be focused on establishing the criteria for
      safety and efficacy of interventions based on alternative health belief systems,
      on understanding the "meaning" response and on clinical/epidemiologic research on
      a carefully selected small number of alternative interventions based on their
      "plausibility." Novel ways of surveillance of the safety of alternative therapies
      should be supported in place of the planned system modelled on the program for
      drugs.

PMID- 12811078
TI  - Maturation of complementary and alternative healthcare in Canada.
AB  - Complementary and alternative medicine (CAM) use is increasing rapidly in Canada.
      This use is mostly driven by consumer demand. While this field of research is
      relatively new, it is maturing rapidly. This commentary highlights three areas of
      increasing maturation: the emergence of integrative healthcare; the development
      and application of new approaches to investigating CAM and integrative
      healthcare; and the development of a research infrastructure to support these
      developments. It is encouraging, the authors note, that organizations, networks
      and federal agencies such as the Canadian Institutes of Health Research and
      Health Canada are collectively and collaboratively identifying barriers to these
      developments and are developing strategies to overcome them.

PMID- 12811079
TI  - Complementary and alternative medicine: how do we know if it works? Time to find
      out!
AB  - The use of complementary and alternative medicine (CAM) in Canada is increasing.
      This may be due to a variety of factors, including limitations of current therapy
      and patient perceptions of safety. The increasing use of CAM is exposing large
      numbers of patients to various forms of CAM Commentary - patients who might be
      very different from the populations who have traditionally used the type of CAM
      in question, including children and pregnant women. It is critically important
      that therapies involving CAM be evaluated for safety, efficacy and cost
      effectiveness in order to determine where they might fit in the healthcare
      system. One potential approach is the creation of a Canadian Institute of
      Therapeutics, with a broad mandate to evaluate conventional, complementary,
      alternative and novel therapies. Such an Institute, in partnership with
      investigators and conventional and CAM practitioners, might provide a focus and
      impetus for studies to define where CAM and other therapies are best configured
      in the Canadian healthcare system.

PMID- 12811080
TI  - Complementary and alternative medicine: a pharmacist's perspective on patient
      needs.
AB  - The use of complementary and alternative medicine (CAM) is pervasive throughout
      the Canadian healthcare landscape. The lead paper offers recommendations on
      research, regulation and funding based on accepting evidence beyond that found
      through randomized clinical trials. Unfortunately, the efforts that go into
      policy-making are unlikely to reflect the ever-evolving and plastic nature of
      CAM. Pharmacists have long been the most easily accessible healthcare
      professional and a natural bridge between CAM and conventional medicine. The role
      of CAM, and specifically herbal medications, in conjunction with conventional
      therapy is a dilemma faced by pharmacists every day. Policy-makers need to be
      creative in order to collect data on safety first and then efficacy for a public
      that is already using these services. The quandaries pharmacists face on these
      issues are a microcosm of what researchers and governments must deal with in
      creating policies that respect patient autonomy and at the same time protect
      public safety.

PMID- 12811083
TI  - Negotiating for change. The healthcare manager as catalyst for evidence-based
      practice: changing the healthcare environment and sharing experience.
AB  - This paper addresses the problem of the implementation of both clinical and
      managerial evidence-based decision-making in healthcare. The lack of
      implementation of research findings in clinical and management practice has been
      identified as a key failure in healthcare. Many await the development of better
      methods of research transfer led by academics and clinicians. Research transfer
      has become one of the highest priority are as for health services research. In
      this paper, the authors propose that the healthcare manager is well positioned to
      advance the research transfer process within the individual healthcare
      environment through two main mechanisms. First, healthcare managers can align
      decision-making structures within their own environment to facilitate evidence
      based practice. This can occur by managers demonstrating a commitment to
      processes for the measurement and management of knowledge (identifying knowledge
      stewards) to the same extent that they demonstrate commitment to the measurement
      and management of finances. Within such a framework, the healthcare manager can
      build an environment in which there is an explicit "negotiation" between
      "knowledge stewards" (usually clinicians) and "financial stewards" (usually
      administrators) to achieve a common goal. The negotiation is an explicit,
      documented process that addresses the trade-offs that are made to avoid both
      financial and quality deficits in the organization (the quality deficit is
      defined as the gap between knowledge and practice). The second way in which
      healthcare managers can act as catalysts for promoting evidence-based practice is
      through cataloguing and reporting, using documented stories, the unique barriers
      to evidence-based approaches that are peculiar to their specific healthcare
      environments. It is hypothesized that local contextual circumstances, which can
      be expressed only through stories, are the most powerful barriers to research
      transfer within specific organizations. This has implications for what we count
      as useful knowledge as we try to better understand how rigorous research on the
      one hand and research and stories on the other contribute to strategies for
      research transfer at the organizational level.

PMID- 12811084
TI  - Evidence-based practice in Steeltown: a good start on needed cultural change.
AB  - At the Canadian Health Services Research Foundation we talk a lot about the need
      to improve the 'receptor capacity' for research in the health sector (Canadian
      Health Services Research Foundation 2000). To create a demand for research as
      well as a supply of it. To encourage and assist clinicians, managers and
      policymakers in the health system to pull research from academe with as much
      fervor as applied researchers now bring to publishing it. Browman, Snider and
      Ellis have done more than talk about and encourage these things - they have
      implemented them at their own workplace in Hamilton. Their formula is:1. Design a
      policy-learning forum (Clinical Policy Committee'), where the use of available
      research is encouraged and expected 2. Create champions (knowledge stewards')
      responsible for marshalling and presenting the evidence. 3. Provide rules
      (negotiation') for the dialogue between the operational implications of the
      research and its budgetary reality. 4. Use story telling to uncover local
      implementation barriers and make tacit knowledge explicit. The approach is
      reminiscent of political scientist Paul Sabatier's description of the
      circumstances under which policy learning occurs (Sabatier and Jenkins-Smith
      1993) and Brown and Duguid's compelling outline of how information permeates
      corporate structures (Brown and Duguid 2000). Sabatiers advocacy coalition
      framework highlights the optimal conditions for learning as: balanced coalitions
      (in this case, of those behind the research and those behind the finances),
      enough resources for each side to produce a steady flow of information, an
      organized forum for debate and clear rules of engagement. In 'The Social Life of
      Information, 'Brown and Duguid highlight the extent to which modern corporations
      often leave unrecognized and under-utilized their greatest asset - the tacit
      knowledge accumulated by each employee over his or her career. They, too,
      recommend storytelling as a way to liberate this knowledge for wider use. Browman
      and colleagues 'practical realization of Sabatier' advocacy coalition framework
      and Browns social view of information is refreshing on a number of levels.

PMID- 12811085
TI  - Evidence-based decision-making in healthcare: exploring the issues though the
      lens of complex, adaptive systems theory.
AB  - Browman, Snider and Ellis have articulated several reasons as to why and how
      managers should address the implementation of evidence-based decision-making
      (EBDM) in healthcare. While their observations are acknowledged to be from the
      unique perspective of an oncology setting, this is a timely and welcome lead
      article with significance in other settings. The authors invite opinions on
      transferability, thus forming the basis of this commentary. In response, this
      commentary offers a number of supportive and differing views. Complex, adaptive
      systems (CAS) theory is first addressed as an appropriate lens to reframe our
      conceptualization of the health system. Then, in contrast to negotiation,
      dialogue through participatory planning and decision-making is introduced.
      Evidence-based decision-making (EBDM) and knowledge translation (KT) are expanded
      upon in the context of CAS and participatory environments. Finally, concrete
      suggestions are offered on how to structure multiple-stakeholder involvement in
      the decision-making process, including the growing role of consumers in the new
      complex, adaptive systems reality of healthcare.

PMID- 12811086
TI  - Is sane management possible in a crazy world?
AB  - Most people benefit from healthcare. However, Canadians remain dissatisfied
      because too often we receive faulty care and delayed care, not supported by
      evidence. Browman and colleagues relate successful efforts to introduce evidence
      based care. They show that strong champions can be effective even in insane
      environments. The collaborative approach suggested is moving and thoughtful.
      Sharing between knowledge and financial stewards, including the use of stories,
      is especially valuable when financial stewardshipis not possible because we lack
      information about the local outcomes of care. Goodwill between stewards is
      especially necessary when there are few external incentives to provide excellent
      care. In healthcare good deeds are punished, not rewarded. Canadian governments
      fail to regulate healthcare because of the conflict of interest arising when the
      same group not only regulates care but also functions as insurer, governor,
      administrator and evaluator. We need radical change to eliminate the perverse
      incentives and bizarre management practices that bedevil our healthcare system
      and impede the use of evidence. Fundamental changes in organization and
      evaluation proposed by the Halifax Chamber of Commerce and the Kirby and
      Mazankowski committees will help. Separating the functions of insurer,
      administrator, evaluator and regulator is ethical and necessary.

PMID- 12811087
TI  - Turning evidence into wisdom.
AB  - The evidence on evidence is conclusive. Incorporating evidence in decision-making
      processes can improve decision-making outcomes (Davies and Nutley 1999), but few
      healthcare systems have embraced the use of evidence to the extent needed to
      achieve the potential benefits. Throughout the world, health systems have "not
      delivered the desired health outcomes that are possible with current professional
      knowledge" (Ibrahim and Majoor 2002),. Browman, Snider and Ellis have suggested
      that there has been a lack of systems-level uptake of evidence-based healthcare:
      While systems may have access to the evidence, existing structures and processes
      have not facilitated effective transfer to operations.

PMID- 12811088
TI  - Okay, you asked for stories.
AB  - Storytelling and innovative organizational structures are distinct but
      complementary approaches to tackling the problem of providing evidence-based
      healthcare in hospitals. Both appear to have a great deal of merit. In this paper
      I have used storytelling as a method to expose and analyze three messages in the
      paper by Browman and colleagues: 1) it is possible to create a negotiating
      environment by changing the formal decision-making structure; 2) evidence-based
      healthcare costs more money; and 3) allowing a trial period for an innovation
      increases the likelihood that it will be adopted. Two major challenges are,
      first, to ensure that evidence-based healthcare is valued within both the
      informal and formal organization; and second, to actively involve the most
      important stakeholders--patients--at all levels of policy setting in hospitals.

PMID- 12811089
TI  - The healthcare manager as catalyst for evidence-based practice: changing the
      healthcare environment and changing experience.
AB  - This thoughtful essay conveys a logically ordered series of concepts that may
      help develop a process to more fully integrate evidence into healthcare
      management decisions. In responding to this article we have tried to think
      broadly about what might be discovered if the ideas of Browman, Snider and Ellis
      were put into practice. We have chosen to focus on factors that could confound
      the five-point plan suggested by the authors. Browman, Snider and Ellis provide
      an interesting overview and advocacy for evidence-based medicine and its
      application. The authors recognize that the area under investigation, oncology,
      may lend itself more readily than others to the facilitation of evidence-based
      practice. They introduce the concept of healthcare as a negotiating environment
      and the healthcare manager as a potential catalyst for change. In their
      conclusions the authors offer healthcare managers a five-point plan: 1. Express
      the value that knowledge is a core resource. 2. Structure decision-making to
      involve the stewards of knowledge and stimulate negotiation while encouraging the
      parties to express shared goals. 3. Invest in strategies that support knowledge
      management, including arbitration. 4. Demonstrate leadership and develop
      organizational metaphors to encourage participation. 5. Share the results and
      experiences of evidence-based decision-making.

PMID- 12811090
TI  - A culture of expertise, not conflict.
AB  - Browman, Snider and Ellis propose that managers act as catalysts to institute
      structures for the negotiation of differences between managers and clinicians,
      primarily around the perceived trade-offs between quality care and resource
      allocation. Evidence-based medicine and evidence-based management are required to
      level the playing field, so that quality of care will not suffer "at the expense
      of the business agenda which is easier to measure and manage." But implementation
      of evidence-based management and evidence-based medicine depends on the quality
      of knowledge production and the ability to adapt general knowledge to particular
      organizations. Agreement on guidelines for evidence-based management is
      problematic and complicated by the nature of management research itself. Rather
      than the metaphor of the negotiating environment, which assumes an adversarial
      relationship between management and clinicians, a more fruitful metaphor is the
      expert environment, which assumes a collaborative relationship between the two.
      Management should not only be a catalyst for change but should also assume the
      responsibility of cultivating clinical and managerial expertise at all levels of
      the organization, from custodian to surgeon.

PMID- 12811095
TI  - Planning for Canada's health workforce: looking back, looking forward.
AB  - "Are there enough health professionals in Canada, and will they be there when I
      need them? " Answers to these two seemingly simple questions cover a variety of
      complex and interrelated factors that are not fully understood, as the report
      about Canada's Healthcare Providers (CIHI 2001) makes clear. The report appears
      at a time when Canadian political leaders, healthcare organizations, caregivers
      and others involved with the healthcare system are looking for creative solutions
      to the human resources challenges facing the health system. Many of the issues
      are not new; over the last 50 years they have been raised by various groups and
      government commissions. But there is a sense of urgency today as options for
      renewing and sustaining Canada's health system are actively being explored. This
      essay offers highlights from the report, providing a portrait of what is known
      (and not known) about the people who work in healthcare across the country. It
      makes clear that whether there are (or are not) enough healthcare providers is
      not simply a question of numbers of health professionals. From changes in health
      and healthcare to shifts in the worklife and practice patterns of professionals,
      a better understanding of the wide range of factors affecting healthcare
      providers is essential to further the important debates taking place.

PMID- 12811096
TI  - Planning for Canada's health workforce; past, present and present.
AB  - In a service enterprise, the front line is the product. Health human resources
      issues, however, continue to be treated as simple input problems. More data, in
      and of itself, will not solve health human resources planning challenges. The
      definition of how many and what types of healthcare providers are needed first
      requires a model of delivery of professional services built around professional
      healthcare workers. If we do not get this right, soon the shortage of healthcare
      workers will get even worse as young people choose careers in fields other than
      health services.

PMID- 12811097
TI  - The capacity to change? Workforce growth in the health sector; a U.K.
      perspective.
AB  - Canada is not alone in having to face up to significant human resource (HR)
      challenges as it debates how healthcare should be managed and delivered in the
      21st century. The United Kingdom is having to deal with many similar issues
      related to demographic change, skills shortages and the drive to "modernize"
      public services. This commentary highlights some of the main dimensions of HR
      related change in the U.K. National Health Service (NHS) to counterpoint the main
      messages in the lead paper. The primary focus is on examining the key HR aspects
      of achieving sustained improvement in staffing levels, mix and motivation.

PMID- 12811098
TI  - Healthcare workforce data and policy: local decisions and global implications.
AB  - The invited essay by Alvarez, Zelmer and Leeb provides baseline information about
      Canada's healthcare workforce that invites comparison with similar efforts in the
      United States to collect and analyze workforce numbers, trends and issues. Beyond
      the basic comparisons, such work also provokes discussion and dialogue about the
      intersection of workforce data analysis and policy. Examples of the use of data
      in legislative and regulatory decisions in the United States in general, and
      California in particular, offer some insight into how workforce data can inform
      policy decisions and how such decisions can also be influenced by other factors.
      The possible local and global implications of such policy-making should be
      considered.

PMID- 12811099
TI  - Health human resource planning requires an effective staff retention policy.
AB  - Planning for health human resources requires us to think about the forces and
      factors that attract healthcare professionals to their jobs and keep them there.
      However, the forces for attracting healthcare employees to a job are not the same
      as those factors that keep them there. Without effective recruitment and
      retention policies for healthcare professionals, planning initiatives will
      continue to be ineffective.

PMID- 12811101
TI  - Reflection on past practices is key.
AB  - There is no denying that determining the supply and demand of healthcare services
      is complex, as stated by Alvarez, Zelmer and Leeb in their essay. Many factors
      such as scope of practice, composition of healthcare teams and financing will be
      discussed as Canadians deliberate on the functioning of the healthcare system. As
      we strive to ensure an adequate supply of healthcare providers to meet future
      needs of Canadians, it is key that we reflect on past practices. Furthermore, it
      is necessary to undertake long-range projections, as each issue rests on the
      availability now and in the future of health professionals.

PMID- 12811102
TI  - Health human resources: consider the health technology professions.
AB  - Any analysis of health human resources must take into account the critical
      shortages in the health technology professions, such as medical laboratory
      technology, medical radiation technology, respiratory therapy and other allied
      health professions. These professions are often overlooked or invisible to
      patients, but they provide a vital role in diagnostic and therapeutic services.
      If projected shortages are not addressed, there will be a major impact on patient
      care. Accurate human resources information about these professionals must be
      collected; funding for additional spaces in educational institutions is
      essential; and a reconsideration of scopes of practice to allow more effective
      utilization of health technologists' knowledge and skills should be initiated as
      soon as possible.

PMID- 12811103
TI  - Health human resources: can present trends be altered?
AB  - Predicting the need for health human resources and ensuring an adequate supply
      continues to confound those with a stake in health services. The many
      interrelated factors that influence the demand and supply of health professionals
      seem to exceed our ability to develop strategies that ensure a healthy balance
      between the size of the health services workforce and the needs of Canadians. We
      continue to focus on specific health disciplines rather than considering
      alternatives and implementing policy options that recognize the interdependence
      of health professionals.

PMID- 12811104
TI  - Scarcity of health human resources: a chronic national disease.
AB  - If one looks at the past and present concerns about health human resources in the
      country, it seems that the health human resource question might be characterized
      as a chronic national, now international, disease. As a disease, it causes much
      stress and attendant fatigue, and when there are acute exacerbations it
      debilitates our healthcare system. Management of this malady will require a
      committed national effort directed in several areas. These areas include
      establishment of an enhanced national database of healthcare professionals,
      further research into the areas of recruitment, retention and renewal, and the
      development of a national overarching framework for managing this complex
      problem. Finally, there is a need to clarify the roles of both the provincial and
      federal governments in bringing long-term stability to the health human resources
      workforce in Canada.

PMID- 12811107
TI  - Drug policy: making effective drugs available without bankrupting the healthcare
      system.
AB  - To the extent possible, drug policy should be based upon good quality evidence.
      This must extend beyond the traditional focus on efficacy and safety in carefully
      selected patients, to evidence about real-world effectiveness, cost-effectiveness
      and safety of drugs. This paper will consider methods of improving the quality of
      the evidence currently available, and the implications of requiring that
      evidence. Historically, there has been a direct link between research evidence
      and policy at the level of licensing - drugs are only made available after they
      have been shown to be safe and efficacious in well-designed and independently
      assessed research studies. We propose that this reliance on evidence be logically
      extended to cover the formulary inclusion and post-marketing surveillance aspects
      of modern prescription drug policy. More specifically we propose that the
      decision to initially list a drug on a benefit formulary be based on evidence
      from relevant head-to-head comparisons and well-designed cost-effectiveness
      analyses. This evidence would be produced by industry in cooperation with
      independent peer-reviewed funding agencies. Drugs could only be added to a
      formulary if they met specific predetermined criteria, and drugs could be removed
      as superior alternatives became available. The provincial governments are
      monopsony buyers of medicines, and they wield the power to determine public payer
      "market access'for medicines. This power (within and across provinces) could be
      used more effectively to negotiate price in the context of reimbursement. The
      effect of different methods of influencing prescribing (e.g., 'limited access?)
      upon drug utilization and patient outcomes should be rigorously assessed,
      including the randomization of groups of patients or communities to different
      strategies. We also propose that all drugs on the formulary would be subject to a
      well-designed post-marketing surveillance program. This program would build on
      the existing passive reporting of adverse events by adding a proactive system
      that would systematically describe the use and impact of drugs. The notion of
      drug safety would be extended to include not only adverse events, but also
      inappropriate use of drugs that results inpatients receiving drugs that do not
      benefit them. Inappropriate use wastes resources and can put patients and
      populations at risk.

PMID- 12811108
TI  - Getting the cat back in the bag: reforming the way provinces manage drug
      expenditures to make them manageable.
AB  - The fiscal "cat" of healthcare spending - drug expenditures - is out of the bag:
      drug costs are now the fastest rising component of healthcare expenditures in
      Canada. Laupacis, Anderson and O'Brien describe the current process of listing
      drugs on the provincial drug formulary in Ontario, identify factors that may
      contribute to the rapid growth in drug expenditures, and make a number of
      recommendations for controlling drug expenditures, including (1) improving the
      evidence on cost-effectiveness; (2) disseminating the evidence to prescribers;
      (3) re-evaluating the evidence; and (4) increasing the transparency about the
      acquisition costs of drugs. These are recommendations that, if implemented, would
      theoretically help decision-makers make more rational decisions about which drugs
      to list on provincial formularies. The question of how to implement the
      recommendations remains to be elucidated, as does an evaluation of the trade-offs
      between costs and benefits of obtaining better information on cost-effectiveness.

PMID- 12811109
TI  - Drug policy: the challenge is to overcome fragmentation.
AB  - Laupacis, Anderson and O'Brien present a number of well-informed suggestions for
      improving the cost-effectiveness of prescription drugs by improving available
      information. Their suggestions cover the various stages of drug development and
      utilization from the way clinical trials are designed to the information
      collected on drug effectiveness after the drug is licensed for use. While
      improved information alone will not control drug costs, these suggestions, if
      implemented, should improve our ability to use drugs in more cost-effective ways.
      A significant challenge, however, will be creating a comprehensive approach to
      information that overcomes the fragmentation characteristic of current
      arrangements.

PMID- 12811110
TI  - Let evidence be the arbiter.
AB  - Methods for evaluating drugs to ensure there is value for money spent have been
      debated for years. There have been many attempts at controlling the use of drugs
      starting with formularies, limited listings for specific uses and the negotiation
      of prices. The strategy put forward by the lead authors would be helpful to all
      parties. Their proposal would allow evidence to be the arbiter and provide
      information that is understood by all concerned. It would take courage by all
      interested parties to accept these ideas. However, the time is right for the
      adoption of a better way to keep drug programs affordable without denying anyone
      the treatments that can make a difference to their health.

PMID- 12811111
TI  - More of the same is not enough.
AB  - Growth in pharmaceutical expenditures in Canada is approximately double the rate
      of growth in other healthcare expenditures. Conventional approaches to
      controlling expenditures are not working. The policy options proposed by
      Laupacis, Anderson and O'Brien for managing pharmaceutical budgets--better
      evidence, better dissemination, additional regulation and increased dialogue--are
      necessary but not sufficient to bring about more cost-effective prescribing. This
      paper suggests three additional strategies that will complement existing
      policies: restructuring consumer co-payments such that consumer cost-sharing
      varies inversely with therapeutic necessity; introducing physician budgets for
      those pharmaceuticals for which there is reasonable suspicion of overuse; and
      price-volume contracting with pharmaceutical firms, consistent with evidence from
      pharmaco-economic evaluation. The first strategy will send better signals to the
      consumer as to the value of the pharmaceuticals they are consuming. The latter
      two strategies will provide incentives for physicians to prescribe and industry
      to market their pharmaceuticals in a fashion more consistent with cost-effective
      use of these drugs. Better evidence and better dissemination are simply not
      enough.

PMID- 12811112
TI  - Drug policy: an oxymoron?
AB  - The use of the words "drug" and "policy" together highlights some of the
      inconsistencies and ironies in healthcare delivery in Canada. Not that the
      legislators and the government mandarins don't try to create and implement
      policy, but events (and the pharmaceutical industry) are always one step ahead so
      the policy-makers find themselves in the role of "follower" rather than "leader."
      It is time to re-examine the current approach to decision-making about
      pharmaceuticals and to identify a process that allows all Canadians to receive
      the care that was promised with the passage of the Canada Health Act.

PMID- 12811113
TI  - Drugs, health and the economy: investment, innovation, outcomes, growth.
AB  - Sustainability of the Canadian health system is currently foremost in the minds
      of many stakeholders. Historically, health expenditures have been viewed as ever
      increasing and with little visible economic return. Recently, economists have
      recognized the health arena as an important growth area within the total economy
      and have begun quantitative analyses of the impact of health investments as
      drivers of innovation and the general economic advance of nations. In particular,
      evidence has focused on the discovery and diffusion of new drugs as practical
      reflections of the quality ladder model of innovation, largely through their
      provision of improved duration and quality of life and accompanying productivity.
      The rate of return on innovative drug therapy within the universe of patients who
      could benefit is, however, impeded by under-prescription of, restricted access
      to, and/or impaired compliance with, newer efficacious drugs. The authors support
      further research to assist in future health policy decisions, including wider
      testing of the partnership/measurement model of disease management as a feasible
      tool to optimize the social rate of return on already-proven drug therapy. They
      further recommend these partnerships be designed with enough breadth of vision to
      facilitate their transition to operational projects compatible with evolving
      public health policies.

PMID- 12811114
TI  - Managing healthcare costs within an integrated framework.
AB  - Laupacis, Anderson and O'Brien's comprehensive diagnosis of the illness affecting
      the Canadian healthcare system is very insightful. In addition, their call for
      improving the quality of drug evidence and outcomes is a laudable goal. However,
      their prognosis of the negative impact on healthcare due to escalating drug costs
      appears to be rather pessimistic, as they fail to view drugs within an integrated
      framework. In part, their prescription for the perceived malady is rather
      impractical. Their recommendation for mandatory head-to-head randomized studies,
      as a prerequisite for achieving new drug listing in benefit formularies, suffers
      from many drawbacks. Such studies would be highly time-consuming, extremely
      costly, and given the fact that the choice of a drug comparator is a "moving
      target," the end result may not achieve the original intent. Growing anxieties
      about the rising healthcare costs in Canada, now forecast to reach C$100 billion
      in 2002, have led to implementation ofa variety of reforms aimed at cost-cutting.
      Shifts in drug utilization, demographics and prescribing have contributed to the
      authors' understandable concern about the rapid rise in drug plan expenditure,
      which has undeniably outpaced the increases of other healthcare components.
      However, drug plan costs represent only 7.7% of total provincial/territorial
      healthcare expenditures. Innovative medicines have played a significant role in
      reducing the burden of illness and overall healthcare costs. Drugs prevent, treat
      and cure disease, improve quality of life, control pain/suffering and save lives.
      Despite their great value, spending on drugs has received particular scrutiny
      from policy-makers, and pharmaceuticals have become the primary cost-containment
      target. The authors' goal-oriented concept of creating a clinical milieu that
      encourages cost-effective prescribing via "optimum" drug use is very attractive.
      One such approach is Disease Management, which relies on evidence-based, outcome
      oriented performance indicators. It is highly regarded for promoting effective
      treatment options, improving patient care and optimizing healthcare resource
      utilization--hence deserving serious consideration for reducing overall costs
      while achieving improved outcomes.

PMID- 12811115
TI  - Look beyond budgets to the broader benefits.
AB  - The success of researchers in developing innovative and effective medicines has
      produced a healthier and older population, as well as an observable shift in
      expenditure towards pharmaceuticals. In contrast to drug expenditures, patented
      drug prices have actually shown an average annual decrease of 0.5% since 1988.
      While we agree cost-effectiveness evaluation is a useful input into the decision
      making process of drug benefit managers, it is but one consideration, and it is
      imperative that governments look beyond drug budgets to the broader benefits of
      innovative drug therapy to Canadians, both economically and clinically. The lead
      paper makes a number of suggestions regarding clinical trials that would lead to
      an increased demand on the developers of innovative medicines, all of which would
      raise the development costs of drugs while reducing the spectrum of available
      agents. This commentary argues that focusing greater attention on ensuring the
      appropriate use of medicines, with less concentration on restricting Canadians'
      access to effective drugs available in other countries, will yield the greatest
      benefits to the health of our population. Patient health management is a strategy
      that deserves a closer look to achieve this goal.

PMID- 12811116
TI  - Our advice? Get a budget!
AB  - Laupacis, Anderson and O'Brien propose amending regulations to get better
      information so that effective drugs can be made available without bankrupting the
      healthcare system. We reckon that this proposal is rather like shutting the barn
      door after the horse has bolted. If you want to avoid bankruptcy, first you have
      to know what you can afford to spend. From our observations as a public agency
      responsible for setting drug subsidies in New Zealand, operating within a budget
      constraint may better help to achieve many of the desired outcomes.

PMID- 12811119
TI  - A framework for reform. Highlights from the Report of the Premier's Advisory
      Council on Health.

PMID- 12811120
TI  - Decoding Mazankowski: a symphony in three movements.
AB  - The Mazankowski Report is ingenious in design. It is in fact a report in three
      movements. It begins with a well-modulated analysis of internal reforms needed to
      improve the system, generally harmonious with the prescriptions of other national
      and provincial reports. Its financial analyses are composed in a more ominous
      minor key. Its defining moment is a jarring ideological crescendo that may turn
      out to be its legacy in the Canadian healthcare debate.

PMID- 12811121
TI  - Maz confusion? Reflections on a framework for reform.
AB  - While the recent Mazankowski Report offers many wise suggestions for how the
      health system might be strengthened and the health of the population improved,
      some of the other ideas it presents are not so meritorious. These are most
      notable in the recommendations related to finance, where the Premier's Advisory
      Council has relied more on rhetoric than on evidence.

PMID- 12811122
TI  - A healthcare "trojan horse": the Alberta Mazankowski report. An analysis of a
      framework for reform: the Report of the Premier's Advisory Council on Health in
      Alberta.

PMID- 12811123
TI  - Making health spending work.
AB  - Medical Savings Accounts (MSAs) are usually promoted as a demand-management tool
      that gives consumers incentives to economize on medical expenses. "Making Health
      Spending Work" takes the concept one step further and shows how MSAs can be used
      to design a publicly funded system that incorporates market dynamics. MSAs can
      bring efficiency-enhancing incentives to the supply side, creating consumer
      choice and empowerment with a public system that meets Medicare's key principles.
      Over the last few months, Canada's political leaders have begun to break away
      from the reform-stalling tactics of special interest groups - which profit
      mightily from the the current system - and to examine sensible reforms that could
      benefit all Canadians. By breaking free of old dogmas, Canada can turn myth into
      reality: we can have the best medicare system in the world, one that expands
      choice and creates efficiency-enhancing dynamics.

PMID- 12811124
TI  - The Mazankowski Report: radical solutions in innocuous wrapping?
AB  - On the surface, the Mazankowski Report appears highly conventional. The flaws in
      the current health system that it identifies - lack of service integration,
      inadequate human resource planning, insufficient information to manage the system
      appropriately - and the solutions proposed will be familiar to aficionados of
      health commission reports from the last decade. However, the report does depart
      from the current Canadian consensus in two important respects: first, it views
      ensuring access to some types of health services as explicitly an individual,
      rather than a collective, responsibility; second, it recommends funding access to
      such services through mechanisms that will likely create financial barriers to
      care for less healthy or affluent Canadians.

PMID- 12811125
TI  - Why do folk clutch at straws when there is a lifeboat on hand?
AB  - The Mazankowski committee considered all too familiar problems with the Alberta
      healthcare system, in particular expenditure inflation and public
      "affordability," and the efficiency of the provision of care to the population.
      The remedies if offers are incomplete and unconvincing because of the failure to
      use rigorously the evidence base. Is the system unaffordable when the modest
      effects of the aging of the population and efficient health technology assessment
      could control inflation? Why advocate "competition" when it is not defined and
      managed care in the United States has failed? The Council's report glosses over
      the crucial issues of how physicians ration healthcare in Alberta and how the
      profession has failed to evaluate and manage major variations in medical activity
      and outcomes. Investment in these areas together with global budgets and
      equitable financial allocations offers better health for the Alberta population.
      Many of the Council's proposals are not consistent with the goals of expenditure
      control, equity and efficiency.

PMID- 12811126
TI  - The Mazankowski Report: can we fix medicare with more private financing.
AB  - The Mazankowski Report is a very important contribution to the debate washing
      over Canada with regard to the future of its most cherished social program,
      medicare. While a complete analysis of the report is not possible in this brief
      comment, several observations and arguments should be made. First, the report's
      recommendations for a greater role for private financing undermines the other
      excellent recommendations made with regard to greater accountability, the
      rigorous pursuit of quality and greater flexibility regarding the role of the
      private sector in delivery (as opposed to financing). Second, the report's
      specific recommendation to establish a permanent, independent panel to determine
      what services should and should not be publicly funded is a worthwhile reform,
      but not for the reasons envisaged by the report's authors - that is, because it
      will result in a reduction in the range of services funded and save public
      dollars. Rather, it is a worthwhile initiative because engaging in a transparent
      and explicit determination of what is in and out of the publicly funded basket is
      likely to result in more political support for publicly funding a wide range of
      care rather than less.

PMID- 12811128
TI  - Academic health sciences centres laid bare.
AB  - Academic Health Sciences Centres (AHSCs) are an enduring feature of health
      systems in all developed countries. In Canada, despite the lack of precise
      definition and standardized organizational arrangements, the educational services
      and programs in health sciences offered by AHSCs, and the caregiving
      organizations they embrace, are critical components of the national health
      system. Yet, the past decade has been a period of profound change in the Canadian
      health system. The pace of this change and the nature of the demands on the
      system are unlikely to abate in the near future. Given that many of these changes
      have directly impacted on AHSCs, or their component parts, it is timely to review
      these entities and to understand more fully how these organizations have been, or
      may be, affected in the future.

PMID- 12811129
TI  - Academic health sciences centres: a view from the academy.
AB  - Academic Health Sciences Centres have provided and continue to provide valuable
      service to society. However, the lack of a clear mandate, structure, governance
      and administration results in their full potential not being met. As the Canadian
      healthcare system undergoes the reform that must occur to make the publicly
      funded system sustainable into the future, it is essential that AHSCs have
      clarification of their roles, develop a distinct governance structure and be
      provided a distinct budget for a set of deliverables within an agreed-upon
      accountability framework.

PMID- 12811130
TI  - Begin with ethics. The rest will follow.
AB  - Solutions to some of the challenges facing Academic Health Sciences Centres
      (AHSC) might be found in expanding their mandate from the traditional tripartite
      definition - teaching, research and patient care - to include an equally
      important fourth mandate - responsibility to the community. Indeed, it could be
      argued that the current movement towards community-based teaching will exert such
      funding and organizational pressure on AHSCs that fundamental change will be
      forced upon them.

PMID- 12811131
TI  - AHSCs: more important than ever in the century of health research.
AB  - We are in the midst ofa profound revolution in health research, a revolution
      being driven by our emerging understanding of the molecular basis of life and
      human disease. This revolution is creating a century of health research,
      characterized by the convergence of virtually all disciplines, from mathematics
      to the social sciences and humanities. This convergence of disciplines is
      introducing radical changes and opportunities in the discovery and R&D process of
      health research. Academic health sciences centres (AHSCs) are strategically
      placed to contribute to, and benefit from, this revolution. To that end AHSCs
      require exceptional visionary leadership, a commitment to clinical and research
      excellence, a full appreciation of the complete tripartite mission of AHSCs, and
      the development of an outward-looking stance that includes the development of
      public policy. The federal governments clear and sustained commitment to health
      research, as demonstrated recently by the 15% increase to the Canadian Institutes
      of Health Research budget, provides an important opportunity for AHSCs to
      demonstrate their crucial role in both the development of an innovative and cost
      effective healthcare system and to Canada's broader social and economic agenda.

PMID- 12811132
TI  - The embattled academic health centre.
AB  - Lozon and Fox have provided a thoughtful analysis of Canadian academic health
      centres. However, their account is incomplete. Their emphasis on the "shared
      purposes and goals" of the component groups of academic health centres overlooks
      the profound tensions and disagreements that have always existed between medical
      schools and teaching hospitals. In addition, their claim that academic health
      centres "have endured in more or less the same form throughout their history"
      ignores the profound growth, changing organization and evolving missions that
      have characterized these institutions for over a century. Lastly, they do not
      address the most profound dilemma of all of the academic health centres: that
      current financial pressures are causing an erosion of their educational work.
      These three aspects of academic health centres are discussed in this commentary.

PMID- 12811133
TI  - AHSCs: the movement from brokers of scarce resources to victims of the changing
      environment of healthcare delivery.
AB  - Academic health sciences centres in both the United States and Canada, once major
      "brokers" of medical and biomedical knowledge and other scare resources, are
      frequently depicted as "victims" of the environments in which they exist. While
      the national and local environments in which these organizations exist differ
      substantially, the integrity of AHSCs in both nations is threatened by a variety
      of emergent and continuing externalities. It is important that AHSCs develop a
      sufficient vision and market to be self-determining and successful in countering
      pressures that challenge their teaching, research and service activities.
      Leadership in both Canada and the United States must become much more skilled in
      strategic management to achieve this goal.

PMID- 12811134
TI  - AHSCs: an indispensable partner for governments.
AB  - A closer relationship between Academic Health Sciences Centres and governments
      will benefit the overall agenda of health system reform, contribute to the focus
      and immediacy of the future vision of AHSCs and give governments a deep pool of
      expertise from which to draw in facing significant policy challenges. Jointly
      established priorities in health between federal, provincial and territorial
      governments correspond closely to the interests and expertise of AHSCs. A mutual
      commitment to evidence as the basis for making decisions in health policy, in
      education, and in patient care, will find expression in closer interaction
      between these two institutions.

PMID- 12811135
TI  - Governments, policy directions and the future of academic health sciences
      centres.
AB  - Governments and the policy-making bureaucracy are faced with all of the
      challenges currently facing academic health sciences centres (AHSC).
      Traditionally, AHSCs and their faculty partners were key players in the
      development of policies that defined the directions of the healthcare system. A
      better understanding of the determinants of health, demands for new community
      services and an inflexible workforce are forcing governments and policy-makers to
      re-evaluate the role and responsiveness of AHSCs as directions are set for the
      system of the future. AHSCs must engage policy-makers f they expect to continue
      as a major influence in the direction of a Canadian publicly funded health
      system.

PMID- 12811136
TI  - AHSCs: the complex simplicity of service.
AB  - The literate and effective dissection of the problems of the modern Academic
      Health Sciences Centre (AHSC) represents a significant contribution by Lozon and
      Fox. However, the fundamental issues may be both simpler and more intractable
      than they describe. The hospitals, medical schools and research institutes that
      compose the AHSC have individually and collectively drifted away from an ethos of
      service with the patient at its centre. Systems theory teaches us that "emergent
      behaviour' wherein the AHSC becomes more than the sum of its parts will only be
      achieved when there is commitment to a common purpose aided by mutual respect and
      the generalist perspective necessary for its full expression. As social and
      health trends underscore and support the need for aggregative and problem focused
      education and research, it is not clear that AHSCs are reacting in an effective
      way - increased isolation from community and generalist care leaves highly
      specialized institutions vulnerable to criticism of both irrelevance and sub
      optional care. A re-affirmation of unambiguous commitment to both study (research
      and educate) as well as serve those who suffer provides the most likely avenue to
      make the 21st century'the best of times 'for the AHSC.

PMID- 12811137
TI  - The disconnect of twin pillars: the growing rift in educational goals and methods
      between medical schools and the academic teaching hospitals.
AB  - Academic teaching hospitals (ATH) and medical schools are the two main components
      of the Academic Health Sciences Centre (AHSC) organization. They have
      traditionally worked in a symbiotic, f relatively unstructured and somewhat fluid
      relationship. Now changes in the medical school approach are creating stress on
      this traditional partnership. First, medical schools are being driven by external
      pressures to better respond to societal needs. Medical schools are increasingly
      decentralizing their educational process to help produce physicians with the
      values and skills needed to meet the diverse needs of Canadian society. Second,
      internally, the changing nature of medical knowledge and skill sets has led to
      differences in the educational process with more formal standards and educational
      goals. Within this second change is a difference in the trainees moving through
      the educational system - today's future doctors represent a different value set
      and demographic profile than their predecessors. These changes pose both a
      challenge and an opportunity for ATHs. ATHs are well positioned to be leaders and
      facilitators of these changes. Doing so would help strengthen the system, and
      would ultimately help ATHs fulfil their complex and often competing mandates.
      Unfortunately, there are also incentives for ATHs to fight these trends. The
      response of ATHs to their evolving relationship with medical schools and
      universities will have a large influence on the future shape and function of the
      AHSC.

PMID- 12811138
TI  - Solutions must include the community hospitals.
AB  - The authors of this commentary acknowledge that Academic Health Sciences
      Centres(AHSCs) will need to change, but they assert that the need for change and
      urgency are even more dramatic than presented by Lozon and Fox. While the AHSCs
      are likely to survive, their form and fabric are likely to change dramatically in
      the new order. Any solutions to the problems of the AHSCs have to include the
      community hospital stakeholders, especially the evolving regional teaching
      hospitals. This applies not only to patient care but also to the potential
      teaching and research (clinical trials) contributions of the community/regional
      players. There must also be more involvement by non-medical faculties in defining
      the vision, mission and values of the AHSC. Federal funding should be available
      not only to enhance the research activity of the AHSCs and the regional partners
      but also to provide the informatic linkages between players. Alternative funding
      programs for academic physicians along with enhanced productivity measures in
      areas of patient care, education and research are important in order to level the
      playing field not only with respect to remuneration but also with respect to
      other incentives such as recognition and promotion.

PMID- 12811141
TI  - Physicians, thou shalt ration: the necessary role of bedside rationing in
      controlling healthcare costs.
AB  - Physicians are often asked to be "gatekeepers," determining their patients'
      access to medical therapies and technologies. At the same time, most physicians
      have been taught that they should act as patient advocates, pursuing patients'
      best interests regardless of cost. This paper reviews moral arguments ethicists
      have made for and against "bedside rationing." It argues that healthcare
      rationing is appropriate in order to help control healthcare costs, and that
      rationing decisions made at the bedside by physicians must be part of the
      rationing system. A system that attempts to control costs by mandating an
      elaborate set of rules would be burdensome, and many physicians would find ways

PMID- 12811142
TI  - The tragedy of the Medicare commons?
AB  - Peter Ubel's main conclusion is that physician participation in bedside rationing
      is essential to controlling healthcare costs. This conclusion is out of step with
      the current focus of thinking and policy debate within Canada and other countries
      with universal public healthcare systems. In the Canadian context, collectively
      we need to better understand the limits and choices in defining the "medicare
      commons," which occurs at the intersection of the overall level of funding, the
      range of services provided (comprehensiveness) and the level of access that we
      are able to provide. This will require a deliberative process that must engage
      patients/the public at all levels of decision-making. Physicians must accept
      responsibility to use scarce resources prudently, but this is a collective
      responsibility and must be exercised in a transparent manner.

PMID- 12811143
TI  - Rationing healthcare: the appeal of muddling through elegantly.
AB  - There is no denying the existence of rationing in healthcare. It is an example
      par excellence of a "wicked issue." Faced with the reality of rationing, the
      issues are: who should ration, and how rule-bound and explicit should it be?
      Clinicians are ambivalent on these matters. Many would prefer governments and
      politicians to make these decisions openly in publicly funded healthcare systems,
      since they decide how much to spend on healthcare. Others believe it to be the
      responsibility of clinicians to decide how finite resources should best be used
      in individual cases.

PMID- 12811144
TI  - Cutting healthcare costs without rationing at the bedside: preserving the doctor
      patient fiduciary relationship.
AB  - In his essay on bedside rationing, Peter Ubel argues that in an era of rising
      healthcare costs, it is time to relax the patient-centered ethic of physicians as
      unconditional patient advocates so they can individualize rationing decisions.
      This paper raises several concerns with the arguments and the examples he
      provides to make his case. First, he overlooks cost-effectiveness when making
      medical spending decisions. Second, his examples of wasteful, unproven and
      potentially harmful interventions call for physician education, not rationing, as
      he suggests. Third, informed patients can play a role in lowering costs through
      shared decision making. Fourth, individualized rationing decisions will worsen
      already pervasive disparities in medical care. The paper envisions the ideal cost
      conscious physician as one who is knowledgeable about cost-effective practices,
      avoids unproven interventions whenever possible, and facilitates shared decision
      making through patient education. Such an individual would not, however, withhold
      interventions of proven benefit except when accommodating a patient's preferences
      for a particular therapy. The doctor and patient can only work together within
      the constraints of system-wide rationing if the fiduciary relationship is never
      violated.

PMID- 12811145
TI  - Bedside rationing by physicians: the case against.
AB  - Society should not accept the inevitability of rationing medical resources, at
      least not in the short term. Because of the high degree of waste and duplication
      that characterize the Canadian and, even more, the American healthcare system,
      the invitation to focus on rationing procedures known to be useful is likely to
      divert attention from the need to eliminate waste. If and when extensive
      rationing becomes necessary, however, Ubel's proposal that we adopt bedside
      rationing by physicians ought nevertheless to be rejected because it is ethically
      objectionable. Such a scheme would violate the bond of trust between doctor and
      patient, leading to arbitrary and discriminatory decisions. Since most physicians
      lack both the time and the expertise to perform cost-benefit calculations
      properly, Ubel's scheme would be inefficient as well as unethical. There is a
      better alternative.

PMID- 12811146
TI  - The need is to prioritize, not ration.
AB  - The Canadian model of medicare is based on shared values among governments,
      providers of care and the consumers of care. Rationing implies that a consensus
      exists as to what constitutes the most beneficial medical services and that an
      active decision be made by providers to choose inferior services to save societal
      resources. Such rationing can be arbitrary and non-scientific. A better option to
      prioritize healthcare spending is the development of best-practice guidelines
      that are agreeable to all concerned. Another approach is to reform the system in
      order to optimize the use of facilities, personnel and other resources. Many of
      these reforms will be expedited by the creation of information technology
      linkages between care providers.

PMID- 12811147
TI  - Physicians must participate in establishing standards of care.
AB  - Dr. Ubel has raised an issue with no easy answers. Rationing and the perception
      that we must ration will be with us for the foreseeable future. Physicians must
      participate at all levels in the process to achieve consistent and appropriate
      care. The standard of care provided should be referenced to a societal norm,
      which physicians must help to establish. Physicians must then use that standard
      in individual patient care. This is rationing, and the medical system cannot
      exist without it.

PMID- 12811148
TI  - Advocacy and rationing are compatible.
AB  - In his paper, Peter Ubel attempts to make the case for "bedside rationing" by
      clinicians in order to help control healthcare costs. This commentary addresses a
      number of conceptual, logical and linguistic problems with Dr. Ubel's paper,
      challenges his apparently "heretical" view of advocacy, but provides additional
      support for his central claim that physicians should do bedside rationing.

PMID- 12811154
TI  - Making patients safer! Reducing error in Canadian healthcare.
AB  - Media reports of adverse events experienced by patients raise questions about
      whether these are isolated exceptions or part of a larger problem. There is no
      reliable Canadian data on medical error; but there is little reason to expect
      that the situation differs markedly from Australia or the United States which
      have rigorously studied the problem. Research in Australia has concluded that as
      many as 16% of hospital patients are injured as a result of their treatment. The
      Australian study and more recent research in the United States have created
      widespread concern that an epidemic of error exists in healthcare. Fortunately,
      experts in healthcare and other industries, have pointed toward a number of
      solutions that will reduce these errors. Three key strategies need to be pursued
      First, better information about the numbers and types of errors that occur is
      needed to help pinpoint change efforts. Non-punitive reporting policies must be
      put in place, to assist in altering the traditional culture of blame that has
      discouraged error reporting. Second, a set of strategies have to focus on
      developing more effective systems, including physician-order entry and medication
      administration systems which have been shown to have a dramatic impact in
      reducing errors. These systems are expensive, but their importance in reducing
      injury - and greatly reducing the costs of additional care that come from such
      injuries - make them an essential part of the answer. Finally, healthcare
      organizations need to work to create more effective cultures oriented toward
      preventing errors and intercepting errors that inevitably occur. These cultures
      will require a new emphasis on teamwork, a continual focus on redesigning care
      systems, particularly in high risk areas such as operating rooms, intensive care
      units and emergency rooms. These are not easy tasks and will require investments
      in new equipment and new skills. These steps are essential if we are to maintain
      public confidence in healthcare.

PMID- 12811155
TI  - Better cooperation and less measurement.
AB  - Baker and Norton offer an analysis for tackling medical error that, while not
      wrong, is very traditional in the policy solutions it recommends. The research
      priority should not be better measurement of error, but instead increased
      international cooperation to find solutions to existing problems. For instance,
      rather than developing new databases for mapping errors, existing databases
      should be utilized to create a learning culture that addresses existing problems.
      Within this, understanding errors in primary care is essential,and thus research
      should not restrict the study of errors to clinical situations. Changing the
      culture of medicine is difficult. A model of governance that emphasizes quality
      and accountability may be a mechanism for developing a culture within medicine
      that reduces error and improves patient safety.

PMID- 12811156
TI  - All components of the system must be aligned.
AB  - A culture of safety in healthcare will not be achieved until the fragmentation
      that currently characterizes the delivery system is replaced by an alignment of
      the many component parts, including providers, patients and their families and
      front-line workers on the "sharp end'--physicians, nurses and pharmacists. A
      systemic approach should be introduced that would recognize the interacting
      nature of the delivery system's component parts, and that a change in one
      component of the system will provoke a change in another part. Consumers and
      their families can be empowered through programs that raise awareness, prevent
      error and mitigate its effect when error does happen. Within the system, the
      "safety sciences' can provide guides to effective work processes. Finally, it is
      critical to capture knowledge of what type of error occurs in what place and to
      elucidate strategies to prevent the error.

PMID- 12811157
TI  - Taking responsibility for closing the holes.
AB  - Healthcare leaders must assume responsibility for closing the "holes" in their
      organizations. At the organizational level, this means taking personal
      responsibility for error, making safety an explicit organizational goal and
      building an organization with the people, resources and courage to achieve the
      goal. At the process level, it requires removing unnecessary complexity from
      processes. At the practitioner level, it means changing the design and
      administration of individual roles, and the way individuals work in teams

PMID- 12811158
TI  - Patient safety: cultural changes needed [corrected].
AB  - One essential aspect to improve patient safety and reduce medical errors focuses
      on the need for healthcare organizations to promote a patient-safety culture, and
      to banish the blame and shame culture and "conspiracy of silence"--traditional
      approaches within organizations when reacting to medical errors. Culture change
      arises when physicians, pharmacists, nurses and other self-regulated
      professionals are encouraged and expected to report errors without fear of
      retribution. A culture of patient safety will evolve in healthcare organizations
      and regulatory agencies only if top leaders demonstrate their commitment to
      change by making this a personal priority by assimilating new knowledge about
      medical errors and human behavior. Leaders must also promote strategies to
      integrate patient safety into every process that supports the system of patient
      care delivery.

PMID- 12811159
TI  - Professionals must recognize personal responsibility.
AB  - The recommendations Baker and Norton have developed for reducing error within the
      healthcare delivery system, with their emphasis on non-punitive reporting of
      error, are commendable. However, healthcare practitioners must clearly understand
      that the current medical/legal system has not adopted a similar approach. Courts
      have long recognized the right of victims to compensation for injury caused by
      malpractice or negligence. Individuals will be held to the accepted standards of
      their profession.

PMID- 12811160
TI  - Improving patient safety: just do it!
AB  - Clinicians must celebrate and study medical errors. The dark culture of blame
      must be replaced by a scholarly culture of safety. This commentary presents six
      cases that show what we can learn from errors. The first step to identifying and
      understanding patient safety problems is to develop a common language for
      discussing patient safety. Latent unsafe conditions are ongoing circumstances of
      daily practice that reduce the safety of patients. An error is the failure ofa
      planned action to be completed as intended (error of execution), or the use of a
      wrong plan to achieve an aim (error of planning). Errors can be intercepted by
      appropriate action that minimizes the threat to patient safety. An adverse event
      is any unintended result of medical treatment that results in prolonged hospital
      stay, morbidity or mortality. If an adverse event is caused by an error, or
      series of errors, then it is a preventable adverse event. The teaching hospital
      is the first place where students (physicians, nurses, pharmacists and all other
      disciplines) are exposed to the culture of healthcare. It is essential to expose
      students to a culture of safety early in their training. Clinicians can make
      safety an academically important activity. Clinicians will find it difficult to
      undertake major safety initiatives given the existing constraints on time and
      energy. Although clinicians can identify the safety problems,there must also be a
      commitment to understand safety problems and make improvements. It is strongly
      recommended that hospitals train, implement and support Patient Safety
      Consultation Teams.

PMID- 12811161
TI  - Cutting healthcare costs without preventable clinical incidents--together we can
      improve.
AB  - Medical errors are receiving increasing attention as research results reveal
      escalation in their numbers. Three elements of this complex issue are reviewed. A
      systems approach to reducing the number of errors may be less than effective
      until the negative connotation associated with the phraseology "medical error" is
      changed. Healthcare restructuring, which results in the destabilization of teams,
      is another factor that is related to the increase in medical errors.
      Stabilization of the healthcare environment and/or stronger support mechanisms
      during change are essential. Finally, the litigious sensitivity of the public and
      healthcare systems overall intensifies the "error" element. This element is
      counter-productive to the openness required for the systems approach.

PMID- 12811162
TI  - Medication error and patient safety.
AB  - A number of barriers to the enhancement of patient safety through a reduction of
      medication errors have been identified These include a blame culture; lack of
      leadership;lack of peer-review protection; and the absence of a collaborative
      voluntary national reporting system. The latter would provide oversight and help
      healthcare providers avoid recurrence of these adverse drug events stemming from
      human error.A voluntary practitioners reporting system similar to that promoted
      by the Institute for Safe Medication Practices Canada (ISMP Canada) has been
      shown to be successful in the United States in achieving the goal of enhancing
      patient safety. ISMP Canada needs collaboration with other reporting systems to
      gain more insight and knowledge of the causal factors underlying medication
      errors. This collaborative mode fits into the conceptual model of the medication
      incident reporting and prevention program currently being developed by a
      coalition of key stakeholders including Health Canada, ISMP Canada and the other
      health care professional organizations. The model for a successful patient safety
      enhancement strategy as proposed by Baker and Norton in their lead paper is a
      valid one. In the meantime, there is enough knowledge and information about
      medication errors to permit our putting prevention strategies into practice.

PMID- 12811163
TI  - National agenda: local leadership.
AB  - Cultural change is the first step in addressing the issue of patient safety.
      Strategies to achieve this must be well thought-out and extremely well-executed.
      However, action may be constrained by tension between federal and provincial
      governments. The provincial licensing bodies must be involved in rethinking the
      approach to error. Local leadership stimulated by a national agenda is the best
      way to proceed.

PMID- 12811164
TI  - System performance is the real problem.
AB  - Baker and Norton are right in calling for a study of medical error in Canada, and
      they have provided some very reasonable recommendations for reducing the problem.
      Medical error, however, is just part of a broader problem of performance quality
      in healthcare. The healthcare system itself is now being identified as a major
      cause of illness, death and added costs because of errors, infections, the
      adverse effects of medications, the underuse of effective interventions and the
      provision of unnecessary or inappropriate care. For the healthcare system to
      aspire to the safety level of other modern industries (e.g., airlines) there will
      be a need for: leadership and vision; better data systems and information on
      performance; commitment and skills development among providers; and better
      accountability.

PMID- 12811170
TI  - Home care: it's time for a Canadian model.
AB  - Although all provinces and the territories offer home-care programs, Canada does
      not have a national home-care program, nor are public home-care services covered
      under the principles of the Canada Health Act. As a result, Canadians face
      varying eligibility, cost, quality and access issues to home-care services. Until
      recently, policy makers have had poor information upon which to make decisions
      about the role of home-care programs within the larger health-delivery system.
      This paper includes a review of the most recent policy relevant information about
      home care in Canada as well as descriptions of new models of home care in Canada
      and other countries. Mounting evidence of cost-effectiveness, in combination with
      demographic, health delivery and technological changes, are bringing home care to
      the forefront of Canadian health policy. Other countries are moving forward to
      make home care an equitable and viable option within their health delivery
      systems. Canada could do the same by enacting national home-care legislation in
      partnership with the provinces.

PMID- 12811171
TI  - Home care, continuing care and medicare: a Canadian model or innovative models
      for Canadians?
AB  - Why is home care excluded from the Canada Health Act? In the 1960s, the Hall
      Commission suggested that home care be covered through medicare. History decided
      otherwise--only "medically" necessary care was insured. Today, home-care services
      are provided in conjunction with episodes of hospital care, or are delivered to
      frail individuals as part of their social and healthcare needs. However,
      healthcare can no longer be defined simply as a state of absence of disease.
      Health also includes individuals' physical and mental functional abilities.
      Coverage for health services should include those services aimed at preserving
      and maintaining functional abilities. Moreover, access to home care is
      inequitable in Canada. Financing mechanisms should improve integration of care,
      not increase barriers between medical, hospital and social care. As home-care
      services are provided to persons with different needs, financing and
      organizational mechanisms have to guarantee that resources are distributed most
      effectively to meet these needs. Finally, home-care delivery should adapt to
      local, regional and provincial realities. There is no such thing as "one"
      Canadian home-care model. Already, a number of experiments with home care are
      being implemented in Canada. It is in the search for innovative service delivery
      modalities that Canadians will best be served.

PMID- 12811172
TI  - Developing a home care system by design.
AB  - Developing and implementing a national approach to home care has been an ongoing
      and sometimes controversial point of debate between the provinces and the federal
      government for a few years. We agree that Canada is ready for such a model, but
      the policy instruments imbedded in the model must be carefully considered in our
      commentary we expand on several points made by the lead paper, but focus
      specifically on the proposed model with respect to the suggested policy
      instrument recommended for financing the model and some of the key issues
      surrounding the delivery of home care. It is imperative from our perspective that
      the current political environment be fully understood to appreciate the context
      in which the model would be introduced. We argue t ha t understanding the
      complexities of home care is one thing, resolution of the issues in the model
      proposed is another. Although the federal government has agreed that there will
      be more dollars infused through the Canada Health and Social Transfer, the
      suggested policy instrument recommended for financing the model does not assure
      that home care programs will receive the funding that is required when other
      important and competing interests are considered (e.g., cancer treatment and
      waiting lists). We are at a point where there is incredible potential to
      reconfigure the health system such that home and community-based care can play a
      much greater role, but how do we fully realize that potential? The first step is
      to take the opportunity afforded by the huge surplus of the federal government
      and to invest heavily in developing home care -to create a system by design. That
      means thinking about funding directed to home care as an investment, and not as a
      cost. More funding, however, has limited utility without a sense of where the
      funding should be targeted, and for what purpose. We agree in principle that a
      national approach is required to advance and support home care to meet the needs
      of the future with the correct policy instruments. What happens in the next
      couple of years will shape that long-term model of home care. Whether that be by
      default or design is contingent on the willingness and commitment of the
      politicians and policymakers, and the degree to which the Canadian public have a
      voice that will be heard.

PMID- 12811173
TI  - Health human resource planning in home care: how to approach it--that is the
      question.
AB  - In her paper, MacAdam refers to future challenges in health human resources for
      the home-care sector. This paper builds on her comments and discusses conceptual
      and practical approaches to future planning of health human resources. Necessary
      national data requirements are identified for this type of planning. The authors
      point out the limitations of traditional supply-side modelling and describe a new
      framework linking population health needs to outcomes that builds upon earlier
      conceptual work in needs-based, utilization-based and effective demand-based
      models.

PMID- 12811174
TI  - Clear goals, solid evidence, integrated systems, realistic roles.
AB  - To maximize the effectiveness of home care in improving or maintaining the health
      of Canadians, home-care programs must have clear goals, be founded firmly on
      evidence of effectiveness, form part of an integrated healthcare system and be
      grounded in constitutional and political reality. Goals should be client-centred
      and distinguish between curative, supportive and preventive care. Curative and
      supportive home care can be cost-effective if substitution for more costly
      institutional services can be achieved, but the cost-effectiveness of preventive
      home care and comprehensive care for the elderly has not been clearly
      demonstrated. Integrated delivery systems are a prerequisite for effective
      substitution of care at home for institutional care. Federal financing dedicated
      to a home-care program is unnecessary and is a political and constitutional non
      starter. Federal leadership for a national home-care approach would be welcome.
      Canada Health Act protection for access to medically necessary home care is
      attractive, but such protection for pharmaceuticals is a higher need. Federal
      support for research and demonstration of new models of care is valuable.

PMID- 12811175
TI  - Implementing home care in Canada: four critical elements.
AB  - While MacAdam proposes a "national approach to home care#8221; the obstacles to
      this are well known and substantial. They are the likely cost and the limitations
      of the federal government s role in healthcare. Building on MacAdam's assessment,
      this paper outlines four problems embedded in the various home-care service
      delivery models in Canada: the lack of factual client outcome information to
      support decision-making, the limited client choice of provider, the perverse
      incentive of fee for service and the bias against the for-profit provider. The
      paper proposes that the assessment, classification and measurement of outcomes
      for every recipient of home-care services be standardized using a proven
      assessment instrument, such as OASIS-B or MDS-HC, by healthcare professionals
      certified in its use. The resulting information would be captured in a regional
      database and available for analysis and research. CIHI would be contracted to
      manage a national database and to fund the training and certification of
      assessors. The paper proposes a new service delivery and funding model, utilizing
      standard client outcome information, different roles for regional health
      authorities and service providers, and a prospective payment mechanism replacing
      fee for service. A national home care program may be an elusive dream, but that
      shouldn't stop experimentation, evaluation and improvement.

PMID- 12811176
TI  - Are we finally ready for a Canadian model for home care?
AB  - This commentary argues that there are several elements present today to foster
      the development of the components of a Canadian home care model. The potential
      and limitations of these elements are discussed.

PMID- 12811177
TI  - A living framework: Evolving from traditional care to individual mastery.
AB  - Caught up in the drop-dead pace of change in the world around us, it often
      appears that everything in life is uncertain; yet perhaps, in healthcare, nothing
      is actually changing. Nonetheless, the potential role of home care, which offers
      the flexibility for us to do different things and respond more effectively to
      emerging needs of individuals and families, has always been exciting and offers
      such tremendous promise. There is something quite magical about the relationship
      with clients in their own homes. Healthcare is all about relationships, and with
      today s technologies and other enablers that offer incredible opportunity to
      foster deeper, more meaningful relationships, the potential for home care in this
      new, evolving world is particularly exhilarating.

PMID- 12811178
TI  - Reaching a federal/provincial consensus on home care.
AB  - This commentary agrees with Dr. MacAdam that the time has come to implement a
      national home-care program based on principles similar to those that underpin the
      Canada Health Act. It also agrees with the general thrust of the proposed vision.
      However, it disputes some of the grounds on which Dr. MacAdam's vision is based
      and offers alternative perspectives on key aspects of home care. It concludes
      with a discussion of the issues that will influence the prospects of reaching a
      federal/provincial consensus on a Canadian home-care program.

PMID- 12811179
TI  - Maintaining the integrity of home care.
AB  - The arguments and model put forward by MacAdam are laudable, but fall short. The
      proposal would create a home-care system that is a support system for medical
      care, thus fulfilling only one of the three functions of home care. The emphasis
      in the model on expanding professional services addresses the demands for
      increases in intensive post-acute care. However, the support of chronic long-term
      care and of health promotion and disease prevention would not be strengthened
      and, indeed, would lead to the already visible demise of traditional chronic long
      term care as evident throughout recent health reform. It would ensure that a
      preventive function is not developed.

PMID- 12811180
TI  - Lies told to the sick and weak.

PMID- 12811181
TI  - Bringing healthcare closer to home: one province's approach to home care.
AB  - Ontario is implementing a number of steps to address the growing need for home
      care and continuing care. One of these steps is the establishment of Ontario's
      network of 43 Community Care Access Centres (CCACs). Responsible for aiding
      Ontario residents who seek community-based long-term healthcare, CCACs coordinate
      access to home services such as nursing and homemaking, manage placement to long
      term care facilities and provide information and referral services. In 2000/01
      the Ontario government announced 92.5 million Canadian dollars in new funding for
      long-term community services. This new funding includes 70.1 million Canadian
      dollars for CCACs. During this time, the provincial government will spend more
      than 1.6 billion Canadian dollars for long-term-care community-based services. Of
      this amount, 1.1 Canadian dollars billion will go to CCACs. Community Care Access
      Centres served more than 400,000 people in 1998/99 and are estimated to serve
      more than 420,000 in 2000/01. The administrative funds saved by this province
      wide system are reinvested in front-line health services.

PMID- 12811182
TI  - The "Canadian model" in the international context.
AB  - The focus of this commentary is on the relevance of the Canadian experience for
      developing countries. It highlights the growing urgency poor countries face in
      preserving their major human and social capital--community solidarity and family
      care. Developing countries face a double burden of disease--communicable and non
      communicable diseases alike, with very few, and often shrinking, resources. While
      poorer countries will be able to learn about the essential elements of home-based
      care from the examples of Canada and other industrialized countries, they do need
      to develop their own systems based upon their economic, social, political and
      cultural realities. The primary health care system would seem to provide a
      foundation for the provision of long-term care on a sustainable and cost
      effective basis. In contrast to the often-prevailing practice in developed
      countries, home-based care services could be integrated into the overall health
      and social system. Functional disability, regardless of disease aetiology or age
      of the care recipient, as well as the needs of family caregivers would thus
      become the defining elements of service eligibility. While the question remains
      open as to how much poor countries can learn from the experience of others,
      developing countries do have the opportunity to initiate a rational process where
      they first provide support to communities and informal caregivers and help to
      maintain patients in their homes and only later develop other service elements.

PMID- 12811184
TI  - Rethinking Medicare: response from the Canadian Medical Association.

PMID- 12811186
TI  - Rethinking medicare: it's time to do it!

PMID- 12811188
TI  - Thinking before rethinking: some thoughts about babies and bathwater.

PMID- 12811187
TI  - The key to healthcare reform: context and content.

PMID- 12811189
TI  - Rethinking for today or rethinking for tomorrow? Preparing medicare for the
      future.

PMID- 12811190
TI  - Reframing the discourse: rethinking medicare.

PMID- 12811191
TI  - A redefinition of the issues for rethinking medicare.

PMID- 12811192
TI  - A cautionary tale: rethinking medicare.

PMID- 12811193
TI  - Can medicare be saved? Reflections from Alberta.

PMID- 12811194
TI  - A new role model for healthcare delivery.

PMID- 12811195
TI  - Having choices in healthcare.

PMID- 12811196
TI  - Fact and fiction: The medicare "crisis" seen from the United States.
AB  - There are at present two conflicting images of medicare available to the visitor
      from the United States. One is the conventional media portrait of crisis--from
      both U.S. and Canadian sources--an image of a program in deep trouble, overcome
      by problems of access, cost and quality. The other image is far more favourable:
      medicare as a structurally sound program of universal health insurance that
      largely satisfies those who use it, but, like all programs, requires managerial
      adjustment and attention to the fearfulness of medicare's future that has marked
      the last decade. This is the conclusion of the recent report of the Canadian
      Institute for Health Information (CIHI). Both portraits cannot be accurate, just
      as being green and white all over is logically impossible. What is the American
      interpreter to make of this dispute?

PMID- 12811199
TI  - Ambulatory intraesophageal pH monitoring: the reigning standard for reflux
      monitoring.

PMID- 12811200
TI  - COX-2 and angiogenesis in gastric cancer.

PMID- 12811201
TI  - Detection of Helicobacter pylori in the setting of acute upper gastrointestinal
      bleeding.

PMID- 12811202
TI  - Renal transplantation in HBsAg+ patients: is lamivudine your "final answer"?

PMID- 12811203
TI  - Ambulatory 24-hour esophageal pH monitoring: why, when, and what to do.
AB  - The incidence of gastroesophageal reflux disease (GERD) is increasing and if left
      untreated can lead to significant patient morbidity and even death. The disease
      results from the abnormal reflux of gastric contents into the distal esophagus
      causing symptoms in most and subsequent mucosal damage in some. Several
      investigations can be used to confirm the diagnosis, but most are dependent on
      the presence of sequelae and complications of the disease. The physiologic test
      of ambulatory 24-hour esophageal pH monitoring has proved to be the most
      sensitive and specific diagnostic investigation. It measures increased esophageal
      exposure to gastric juice by detecting the concentration of hydrogen ions (pH <4)
      in the distal esophagus. The technique measures gastric juice exposure at a point
      5 cm above the manometrically determined upper border of the lower esophageal
      sphincter. The exposure is measured in components of frequency of reflux
      episodes, duration of reflux episodes, and accumulated exposure time. The
      components are integrated into a composite score, which is reproducible, gender
      and race independent, and correlates with the degree of esophageal epithelial
      damage determined histologically. The composite score has been shown to be the
      most reliable measurement of a therapeutic acid suppression regimen or an
      effective antireflux operation.

PMID- 12811204
TI  - p27 Protein and cancers of the gastrointestinal tract and liver: an overview.
AB  - GOALS: The purpose of this review is to look at the evidence presented in the
      literature on the immunoexpression of p27 in cancers of the gastrointestinal
      tract and liver. BACKGROUND: Cell cycle proteins have been shown to play an
      important role in the oncogenesis of many tumors. Several of these proteins have
      been examined in concert and in isolation, and some have been put forward as
      putative tumor markers. p27, which is an important inhibitory protein in the cell
      cycle and belonging to a group of cyclin-dependent kinase inhibitors, has also
      been studied in several malignancies, most notably breast, lung, bladder, and
      prostate cancers. Considerable work has also been done on the expression of this
      protein in cancers occurring within the gastrointestinal tract. RESULTS: Cancers
      occurring in the major sites of the gastrointestinal tract (esophagus, stomach,
      and colorectum) and liver show a similar pattern with regard to p27 protein
      levels. p27 emerges as a statistically significant predictor of survival and
      tumor behavior. It has been suggested that p27 loss occurs early in the
      carcinogenesis process, with dysplastic epithelium having decreased expression.
      The more aggressive, metastasizing cancers tend to lack p27 expression as well.
      Some studies have also invoked the subcellular localization of p27 (cytoplasmic
      versus nuclear) as also being of prognostic value. CONCLUSION: Therefore, in
      gastrointestinal and hepatic cancers, low p27 expression is regarded as an
      important adverse prognostic factor.

PMID- 12811205
TI  - Cyclooxygenase-2 overexpression correlates with vascular endothelial growth
      factor expression and tumor angiogenesis in gastric cancer.
AB  - Angiogenesis is a key prerequisite for the successful establishment, growth, and
      dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent
      angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by
      modulated production of angiogenic factors including VEGF. The current study was
      designed to investigate the possible roles of COX-2 and VEGF in gastric cancer
      angiogenesis. In this study, we conducted an immunohistochemical investigation of
      COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor
      angiogenesis, microvessel density (MVD) was determined by CD34
      immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer
      tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The
      expression of COX-2 correlated significantly with VEGF expression. High MVD was
      significantly associated with depth of tumor invasion and poor survival. The mean
      MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than
      that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was
      77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The
      mean value of MVD in tumors positive for both COX-2 and VEGF was significantly
      higher than that in tumors negative for both. However, there was no correlation
      between COX-2 or VEGF expression and various clinicopathological features
      including patient survival. These results suggest that COX-2 may play an
      important role in carcinogenesis by stimulating tumor angiogenesis in concert
      with VEGF in human gastric cancer.

PMID- 12811206
TI  - The usefulness of capsulated 13C-urea breath test in diagnosis of Helicobacter
      pylori infection in patients with upper gastrointestinal bleeding.
AB  - BACKGROUND: H. pylori infection and peptic ulcerations and their complications
      such as bleeding are causally related, but the available methods used in bleeding
      to confirm active H. pylori lack accuracy. AIM To evaluate the usefulness of 13C
      urea breath test (UBT) in diagnosing of H. pylori infection in bleeding patients.
      PATIENTS AND METHODS: Eighty-one patients with upper gastrointestinal bleeding
      and 258 matched controls without bleeding were enrolled to the study. UBT was
      performed using low-dose capsulated 13C-urea and IgG antibodies to H. pylori were
      determined by ELISA. RESULTS: UBT performed in bleeding patients was positive in
      77.7%. In this group anti Hp IgG was positive in 79% of cases and among them
      gastroscopy showed 40.7% of bleeding duodenal ulcer, 38% bleeding gastric ulcer,
      and 86% hemorrhagic gastritis. UBT was positive in 90.9%, 77.4%, and in 52.97%
      cases, respectively, and it was not statistically different from that in non
      bleeding controls, duodenal and gastric ulcers and gastritis. All patients with
      blood or "coffee grounds" in the stomach had both UBT and serology positive.
      CONCLUSION: The UBT is simple and non-invasive method, which can be successively
      applied also in patients with upper gastrointestinal bleeding to detect active H.
      pylori infection prior to emergency endoscopy.

PMID- 12811208
TI  - Treatment of ulcerative colitis using fecal bacteriotherapy.
AB  - BACKGROUND: Although the etiology of idiopathic ulcerative colitis (UC) remains
      poorly understood, the intestinal flora is suspected to play an important role.
      Specific, consistent abnormalities in flora composition peculiar to UC have not
      yet been described, however Clostridium difficile colitis has been cured by the
      infusion of human fecal flora into the colon. This approach may also be
      applicable to the treatment of UC on the basis of restoration of flora
      imbalances. GOAL: To observe the clinical, colonoscopic and histologic effects of
      human probiotic infusions (HPI) in 6 selected patients with UC. CASE REPORTS: Six
      patients (3 men and 3 women aged 25-53 years) with UC for less than 5 years were
      treated with HPI. All patients had suffered severe, recurrent symptoms and UC had
      been confirmed on colonoscopy and histology. Fecal flora donors were healthy
      adults who were extensively screened for parasites and bacterial pathogens.
      Patients were prepared with antibiotics and oral polyethylene glycol lavage.
      Fecal suspensions were administered as retention enemas within 10 minutes of
      preparation and the process repeated daily for 5 days. By 1 week post-HPI some
      symptoms of UC had improved. Complete reversal of symptoms was achieved in all
      patients by 4 months post-HPI, by which time all other UC medications had been
      ceased. At 1 to 13 years post-HPI and without any UC medication, there was no
      clinical, colonoscopic, or histologic evidence of UC in any patient. CONCLUSIONS:
      Colonic infusion of donor human intestinal flora can reverse UC in selected
      patients. These anecdotal results support the concept of abnormal bowel flora or
      even a specific, albeit unidentified, bacterial pathogen causing UC.

PMID- 12811207
TI  - The significance of routine duodenal biopsies in pediatric patients undergoing
      upper intestinal endoscopy.
AB  - GOALS: To determine the significance of performing routine duodenal biopsies
      during upper intestinal endoscopy in a pediatric population and to evaluate their
      contribution to the overall diagnosis. BACKGROUND: Performing duodenal biopsy
      during every upper endoscopy regardless of the indication for endoscopy and the
      macroscopic findings, is a controversial topic. Advocates of performing routine
      biopsies argue that unexpected pathology such as villous atrophy, may have
      significant clinical implications. Opponents argue that the yield of performing a
      biopsy on an apparently normal mucosa is low. STUDY: Duodenal biopsies, routinely
      taken from 201 pediatric patients during upper endoscopy over a 26-month period
      were retrospectively reviewed. Duodenal biopsies taken during this period for
      suspected mucosal lesions were not included in the analysis. Indications for
      endoscopy included suspected peptic disease, gastroesophageal reflux, unexplained
      vomiting, abdominal pain, iron deficiency anemia and Crohn disease. RESULTS: Of
      the 201 sets of biopsies reviewed, 159 (79.1%) were normal, 7 had insufficient
      material for evaluation and 35 (17.4%) carried abnormalities that included: 10
      Giardia lamblia (4.9%), 13 mild chronic inflammation (6.5%), and 8 increased
      intraepithelial lymphocytes (3.9%). Two biopsies showed mixed acute and chronic
      inflammation, 1 showed lymphatic dilatation and 1 had a mild mucosal lesion. The
      risk for microscopic pathology in the duodenum was higher when Helicobacter
      pylori was present in the gastric biopsy (25.98% vs. 12.16% P < 0.02). The
      negative predictive value of a normal appearing duodenal mucosa was 81.5%,
      implying that a normal appearing mucosa does not rule out pathology. No
      complications were encountered in our series. CONCLUSION: We suggest that the
      inclusion of routine duodenal biopsies as part of upper endoscopy in pediatric
      patients should be considered favorably. This practice may yield additional
      pathologic findings that otherwise could have been missed. It should be done
      regardless of the indication for endoscopy or the gross appearance of the mucosa.
      This practice does not increase the risk of the procedure.

PMID- 12811209
TI  - Poor prognosis of colorectal cancer in patients over 80 years old is associated
      with down-regulation of tumor suppressor genes.
AB  - GOALS, BACKGROUND: The elderly population has been increasing during the last
      half a century and it would be important to know how aging influences the
      occurrence and biologic behavior of cancers. STUDY: We investigated
      clinicopathologic characteristics of colorectal cancer in 1354 patients who
      underwent colorectal cancer resection and compared the results between extremely
      elderly patients (over 80 years old) and middle-aged/elderly patients (40 to less
      than 80 years old). Furthermore, we also examined expression of tumor suppressor
      genes and Cox-2 using frozen samples of colorectal cancer obtained from 62
      patients ranging in age from 45 to 87 years. RESULTS: The results obtained in the
      extremely aged patients were: (1) higher ratio of women, (2) higher incidence at
      the proximal site, (3) higher incidence of cases with deeper invasion, (4) higher
      incidence of cases with lymph node metastasis (5) poorer survival rate as
      compared with middle-aged/elderly patients, and (6) lower mRNA expression levels
      of p27 and p53. CONCLUSIONS: These findings taken together suggest that poor
      prognosis of colorectal cancer in patients over 80 years is associated with down
      regulation of mRNA expression of some tumor suppressor genes.

PMID- 12811210
TI  - Sonographic evaluation of bowel wall thickness in patients with cystic fibrosis.
AB  - GOALS AND BACKGROUND: Fibrosing colonopathy causing severe thickening of the
      colon wall was recently described in cystic fibrosis (CF). Since it has been
      suspected that subclinical colon-wall thickening is a common feature in CF
      patients, bowel-wall thickness was measured in a series of patients and compared
      with controls. Additionally, possible clinical factors influencing wall thickness
      were investigated. STUDY: In 83 CF patients and 31 controls transabdominal
      ultrasound was performed in the terminal ileum, cecum, ascending and descending
      colon. The relation of the measured wall thickness to age, sex, pancreatic enzyme
      intake, and intestinal diseases was analyzed. RESULTS: In controls, mean wall
      thickness depending on gut region was 1.1 to 1.3 mm (SD 0.19-0.23). In CF
      patients, no evidence of severe thickening or stricture was found, but wall
      thickness was significantly higher than in controls in all measured regions (1.5
      1.6 mm; SD 0.31-0.41). Patients with meconium ileus and distal intestinal
      obstruction syndrome had significantly increased thickness of the terminal ileum
      compared with patients without these complications. Neither the intake of high
      strength enzymes nor enzyme dosage, age or sex were associated with wall
      thickness. CONCLUSIONS: We found no evidence that a subclinical stage of
      fibrosing colonopathy is prevalent among the CF patients. Slightly thickened gut
      walls in CF can be interpreted as an expression of glandular dysfunction in the
      CF intestine.

PMID- 12811211
TI  - Celecoxib associated esophagitis: review of gastrointestinal side effects from
      cox-2 inhibitors.
AB  - BACKGROUND: With the extensive use of COX-2 inhibitors to treat inflammatory and
      pain syndromes, gastrointestinal adverse effects are being increasingly observed.
      CASE REPORT: An 87-year-old white man with chronic peptic esophageal stricture
      presented to us with dysphagia and odynophagia. The patient was taking Celecoxib
      for 5 months for trigeminal neuralgia. An upper endoscopy revealed severe
      desquamative esophagitis. Celecoxib was discontinued and the patient was started
      on esomeprazole. The patient's symptoms improved in 1 month. Three months later,
      EGD revealed complete healing of the esophageal mucosa. DISCUSSION: Because
      recent studies have shown that COX-2 inhibitors are similar to NSAIDs with
      regards to absorption, in contrast to premarketing trials, extensive use of COX-2
      inhibitors is likely to demonstrate gastrointestinal adverse effects similar to
      those caused by traditional NSAIDs. Our patient had severe esophagitis caused by
      Celecoxib and aggravated by reflux of achlorhydric gastric contents after
      dilatation of the stricture. SUMMARY: We report for the first time severe
      esophagitis caused by the COX-2 inhibitor Celecoxib.

PMID- 12811212
TI  - Excellent outcome of Lamivudine treatment in patients with chronic renal failure
      and hepatitis B virus infection.
AB  - Chronic hepatitis B virus (HBV) is associated with increased morbidity and
      mortality in patients with chronic renal failure (CRF) and renal transplant
      recipients. Lamivudine (3TC) has been shown to be a potent inhibitor of HBV
      replication. It appears to be safe and effective in patients with CRF, though
      experience is still limited. We describe 4 patients with CRF on hemodialysis who
      showed a rapid and full response to 3TC, administered for a median of 10 months.
      All patients had serum alanine transferase (ALT) levels 3 to 6 times the upper
      limit of normal prior to treatment, and different degrees of histologic
      inflammatory activity (Knodell score 4 to 8, median 6). All were serum HBsAg- and
      HBeAg-positive, with serum HBV DNA 1-3.9 x 107 copies/mL (median 1 x 107
      copies/mL). Within 4 to 8 weeks of initiation of therapy, HBV DNA became
      undetectable and serum ALT normalized. Serum HBeAg disappeared in all 4 patients,
      with the emergence of anti-HBeAb in 3 of them. Three patients also lost HBsAg
      with the evolution of a protective anti-HBsAb titer. One patient has already
      undergone successful kidney transplantation with no evidence of HBV recurrence
      (serum HBV DNA negative) 16 months postoperatively. Although our study sample is
      small, these data suggest that 3TC can induce a complete biochemical, virological
      and serological response in patients with CRF and HBV infection. Its use may
      enable safe kidney transplantation in selected patients.

PMID- 12811213
TI  - Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus
      infection with Lamivudine.
AB  - The results of lamivudine therapy in 4 patients with chemotherapy-induced
      hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced
      reactivation is a known complication in patients with chronic HBV infection or
      history of HBV infection with recovery. Reactivation of HBV infection has a broad
      spectrum of manifestations ranging from mild elevation of aminotransferase levels
      to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent
      inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine
      included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging
      from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent
      chemotherapy when they presented with HBV reactivation manifested by sudden onset
      of fatigue, jaundice, and HBV serology consistent with active HBV infection
      (detectable serum HBV DNA) in the absence of other known causes of acute
      hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient)
      was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All
      4 patients showed rapid decrease in aminotransferase levels within 2 weeks after
      initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed
      to improve in 2 patients, who both died. The remaining 2 patients had suppression
      of HBV DNA to undetectable levels after 1 and 4 months of treatment and had
      biochemical and clinical improvement. The 2 patients who died received lamivudine
      therapy for 8 days and for 3 weeks. There have been no randomized clinical trials
      to study the role of lamivudine for prophylaxis or treatment of HBV reactivation
      associated with chemotherapy. However, based on our limited experience,
      lamivudine may be efficacious in suppressing potentially fatal HBV reactivation
      secondary to chemotherapy in patients with chronic HBV infection or prior
      infection with recovery. Patients who undergo chemotherapy should be screened for
      the presence of markers of chronic hepatitis B infection or previous HBV
      infection. We recommend that patients with chronic HBV infection (positive HBV
      DNA and/or positive HBsAg) or history of HBV infection with recovery (positive
      hepatitis B core antibody with or without HBsAb) be considered for prophylactic
      lamivudine use to prevent chemotherapy-induced HBV reactivation.

PMID- 12811214
TI  - Risk of colorectal adenoma in liver transplant recipients compared to
      immunocompetent control population undergoing routine screening colonoscopy.
AB  - BACKGROUND: Immunosuppression following solid organ transplantation has been
      associated with a higher prevalence of cancers including colon cancer. However,
      the risk of colorectal adenoma following liver transplantation is unknown. The
      objective of this pilot study is to determine whether the prevalence of
      colorectal adenoma is increased in liver transplant recipients. METHODS: In this
      retrospective study, 25 patients who had liver transplantation at our institution
      between 1994 to 1997 and who underwent routine posttransplantation colonoscopy
      were compared with 50 controls who were undergoing routine screening colonoscopy.
      Transplant recipients who were younger than 45 years, survived less than 3 years
      following liver transplant, with history of inflammatory bowel disease, or prior
      history of colonic adenoma or cancer were excluded from the study. In both
      groups, colonoscopic diagnosis of polyp was confirmed by pathologic diagnosis of
      adenoma on biopsy. RESULTS: 25 (12M/13F, mean age 53 +/- 7 years) liver
      transplant recipients were compared with 50 controls (19M/31F, mean age of 59 +/-
      7 years). In transplant recipients, colonoscopy was performed 41 +/- 19 months
      after liver transplantation. Seven (28%) liver transplant recipients (5M, 2F) and
      4 (8%) controls (3F, 1M) were found to have adenomatous polyp (OR 4.5, 95% CI 1
      21.2, P = 0.049). Malignant polyps were not detected in both groups. CONCLUSION:
      Liver transplant recipients appear to have an increased risk for developing
      colorectal adenoma. Early screening colonoscopy is warranted for this group of
      patients.

PMID- 12811215
TI  - Endoscopic stenting for postoperative biliary strictures due to hepatic hydatid
      disease: effectiveness and long-term outcome.
AB  - BACKGROUND: Postoperative strictures due to hepatic hydatid disease caused by
      Echinococcus surgery is considered to be a rare cause of benign bile duct
      strictures, especially in the Western world. GOALS: The aim of this retrospective
      study is to demonstrate possible characteristics of the strictures as well as the
      effectiveness of long-term endoscopic stenting. STUDY: Between 1994 and 2001, we
      treated 10 of these cases in our clinic. All patients had surgery for hepatic
      Echinococcus disease one or more times. These types of benign biliary strictures,
      secondary to surgery of hepatic hydatid disease, were multiple and located in the
      proximal common bile duct. Endoscopic stent therapy was carried out in all cases
      containing transpapillary approach with plastic prostheses (7.5-11 French) or
      transhepatic approach with Yamakawa prostheses (16 French). Nine patients were
      available for follow-up. RESULTS: In 6 patients (66%), the stents were removed
      after a median period of 22.5 months with radiologic and clinical signs of
      improvement. Three patients required prolonged dilatation therapy because of
      stricture-recurrence. There was low overall morbidity and we recognized no
      therapy-associated mortality. CONCLUSIONS: Endoscopic stent therapy is a safe
      nonoperative method for the treatment of postoperative benign biliary strictures
      due to hepatic hydatid disease.

PMID- 12811216
TI  - Acute viral cholecystitis due to hepatitis A virus infection.
AB  - Acute hepatitis A virus (HAV) infection is frequent in developing countries.
      Although some gallbladder abnormalities are defined during the course, an acute
      cholecystitis is extremely rare. We here report 2 additional cases of
      cholecystitis due to acute HAV infection and review the previously reported 2
      cases. One of our patients was admitted with jaundice and a suspicious portal
      mass with a presumed diagnosis of cholagiocarcinoma. The other presented with
      jaundice, abdominal pain, and constitutional symptoms. Both patients were planned
      to be operated on. During the follow-up, absence of fever, leukocytosis, acute
      phase protein response, and calculus in biliary system were against the diagnosis
      of a bacterial cholecystitis. Moreover the course of cholecystitis was closely
      parallel to that of the HAV infection. Both patients were managed conservatively.
      It was concluded that rare, acute viral cholecystitis can develop during the
      course of acute HAV infection.

PMID- 12811217
TI  - Colonoscopic identification of a foreign body causing an hepatic abscess.
AB  - BACKGROUND: Hepatic abscesses often result from a perforation of the
      gastrointestinal tract. Although rare, this may occur via puncture by a foreign
      body. The object may directly extend from the stomach or duodenum into the liver,
      or rarely, the object may perforate the bowel distal to the duodenum and
      indirectly extend to the liver leading to the formation of an abscess. CASE
      REPORT: A 44-year-old man developed an hepatic abscess. Although the abscess was
      identified on computed tomography, various imaging studies were unable to
      identify the cause of the infection. After an extended ICU course, the patient
      was deemed stable enough to undergo a colonoscopy that demonstrated a foreign
      body penetrating through the wall of the sigmoid colon. CONCLUSIONS: Here we
      describe the first report of a foreign body leading to a hepatic abscess where
      the object was identified by colonoscopy. In addition, we present a comprehensive
      literature review examining the method of identification of gastrointestinal
      foreign bodies that led to liver abscesses. These findings emphasize that in
      cases of hepatic abscesses of unknown etiology, direct visualization by
      colonoscopy may be a useful tool to elucidate the cause of the abscess.

PMID- 12811218
TI  - Chronic alcohol intake and gastric bicarbonate.

PMID- 12811219
TI  - Is liver disease an octreotide side effect?

PMID- 12811220
TI  - Acute hepatitis B and isolated thrombocytopenia.

PMID- 12811221
TI  - Is hepatocellular carcinoma part of the natural history of nonalcoholic
      steatohepatitis?

PMID- 12811223
TI  - Endoscopic management of bleeding from colonic Dieulafoy-like lesion.

PMID- 12811222
TI  - Severe polycythemia as the first clinical presentation of hepatopulmonary
      syndrome.

PMID- 12811224
TI  - The Rome II Criteria for patients with functional gastroduodenal disorders.

PMID- 12811225
TI  - Are probiotics useful in irritable bowel syndrome?

PMID- 12811226
TI  - Traditional and nontraditional risk factors for cardiovascular and renal disease
      in African Americans (Part 2): a project of the Jackson Heart Study
      investigators.

PMID- 12811227
TI  - From 1960s Evans County Georgia to present-day Jackson, Mississippi: an
      exploration of the evolution of cardiovascular disease in African Americans.
AB  - Cardiovascular disease (CVD) is the No. 1 cause of mortality in the United States
      and it disproportionately affects African Americans. However, there are earlier
      reports that African Americans had significantly less CVD than whites. This
      racial discrepancy in CVD rates was noticed primarily for coronary heart disease
      (CHD). This issue was examined in the Evans County (Georgia) Cardiovascular
      Disease Study conducted in the 1960s. It showed that African American men had
      significantly lower rates of CHD than white men. Over the last couple of decades,
      the rates of CVD have been declining. However, the rate of decline of CVD in
      African Americans has not been equal to that seen in whites, such that African
      Americans now have a disproportionate share of CVD in the United States. In the
      1990s, the Jackson Heart Study was designed to explore the reasons for the
      current racial discrepancy. This articles reviews the findings of the Evans
      County Study and explores various hypotheses for why CVD in African Americans has
      evolved from a disease from which African Americans may have been "protected" to
      one in which they shoulder a disproportionate burden.

PMID- 12811228
TI  - Racism and cardiovascular disease in African Americans.
AB  - This article provides an overview of the evidence on the ways racism can affect
      the disproportionate rates of cardiovascular disease (CVD) in African Americans.
      It describes the significant health disparities in CVD for blacks and whites and
      suggests that racial disparities should be understood within the context of
      persistent inequities in societal institutions and relations. Evidence and
      potential pathways for exploring effects of 3 levels of racism on cardiovascular
      health risk factors and outcomes are reviewed. First, institutional racism can
      lead to limited opportunities for socioeconomic mobility, differential access to
      goods and resources, and poor living conditions that can adversely affect
      cardiovascular health. Second, perceived/personally mediated racism acts as a
      stressor and can induce psychophysiological reactions that negatively affect
      cardiovascular health. Third, in race-conscious societies, such as the United
      States, the negative self-evaluations of accepting negative cultural stereotypes
      as true (internalized racism) can have deleterious effects on cardiovascular
      health. Few population-based studies have examined the relationship between
      racism and CVD. The findings, though suggestive of a positive association, are
      neither consistent nor clear. The research agenda of the Jackson Heart Study in
      addressing the role of racism in CVD is presented.

PMID- 12811229
TI  - Potential role of increased iron stores in diabetes.
AB  - Diabetes mellitus (DM) is an important risk factor for the development of
      cardiovascular disease. Extensive clinical, epidemiologic, and basic studies
      suggest that excessive tissue iron stores may contribute to the occurrence and
      complications of DM. Secondary diabetes occurs in inherited pathologic iron
      overload syndromes of European- and African-derived populations and is an
      established complication of transfusional iron overload. Epidemiologic studies
      have repeatedly shown positive correlation between levels of serum ferritin and
      those of fasting glucose, insulin, and glycosylated hemoglobin. Iron reduction
      therapy in hereditary hemochromatosis and transfusional iron overload is
      associated with improved glucose tolerance and reduced incidence of secondary
      diabetes. Trials of iron reduction therapy in diabetes mellitus, although limited
      and inconclusive, have shown clinical improvement in some patients. The current
      article reviews evidence suggesting that tissue iron contributes to DM and its
      complications and presents preliminary data that emphasize the potential
      importance of iron overload in DM of African Americans.

PMID- 12811230
TI  - Lipid abnormalities and renal disease: is dyslipidemia a predictor of progression
      of renal disease?
AB  - Dyslipidemia is a cardiovascular disease (CVD) risk factor that is associated
      with enhanced atherosclerosis and plaque instability. Renal insufficiency is
      associated with abnormalities in lipoprotein metabolism in both the early and the
      advanced stages of chronic renal failure. These include alterations in
      apolipoprotein A (apo A)- and B- containing lipoproteins, high-density
      lipoproteins, and triglycerides. In animal models, these alterations in lipid
      metabolism and action lead to macrophage activation and infiltration in the
      kidney with resultant tubulointerstitial and endothelial cell injury. Limited
      data in humans suggest that, in addition to contributing to CVD, dyslipidemia may
      be a risk factor for the progression of renal disease. The effects of
      dyslipidemia on the kidney are mainly observed in those with other risk factors
      for renal disease progression such as hypertension, diabetes, and proteinuria.
      Renal disease is a strong risk factor for CVD and African Americans have high
      rates of renal disease. Therefore, examining the effects of dyslipidemia on the
      development or progression or renal disease will be an important question for the
      Jackson Heart Study and is the topic of this review.

PMID- 12811231
TI  - Drug-induced renal failure: update on new medications and unique mechanisms of
      nephrotoxicity.
AB  - Medications cause renal failure through a variety of mechanisms. Hemodynamic
      renal failure may result from drugs that reduce renal prostaglandins and hence
      renal blood flow and glomerular filtration rate. A relatively new group of drugs
      with this potential is the cyclooxygenase-2 selective inhibitors. Direct renal
      tubular toxicity has also been described with a number of new medications with
      unique effects on the epithelial cells of the kidney. These include the antiviral
      agents cidofovir, adefovir, and tenofovir as well as the bisphosphonate
      pamidronate. Additionally, crystal deposition in the kidney may promote the
      development of renal failure. Several different drugs have been described to
      induce crystal nephropathy, including the antiparasitic drug sulfadiazine, the
      antiviral agent acyclovir, and the protease inhibitor indinavir. Finally, an
      unusual form of renal failure characterized by swollen, vacuolated proximal
      tubular cells can develop from hyperosmolar substances. Agents recently described
      to induce an "osmotic nephrosis" include intravenous immunoglobulin and the
      plasma expander hydroxyethyl starch.

PMID- 12811232
TI  - Acute vasculitis with multiorgan involvement in a patient with familial
      Mediterranean fever.
AB  - We report a rare case of a patient with long-standing familial Mediterranean
      fever who presented with sudden onset of dyspnea, abdominal pain, and cutaneous
      manifestations. Chest CT and histologic preparations disclosed pulmonary
      hemorrhage and signs of systemic vasculitis. Cyclophosphamide and steroid therapy
      were initiated, with marked improvement. Based on this and 1 other case, we
      propose that systemic vasculitis should be included as a clinical manifestation
      of FMF.

PMID- 12811233
TI  - Thrombosis and infection: a case of transient anti-cardiolipin antibody
      associated with pylephlebitis.
AB  - Infections with Bacteroides species have been noted to occur in association with
      cases of thrombophlebitis. This association has led to the speculation that the
      microorganisms themselves may contribute to the pathogenesis of thrombus
      formation through elaborated enzymes, including heparinases, or by interactions
      between the clotting cascade and the unique structure of the Bacteroides
      lipopolysaccharide. Anti-phospholipid antibodies have been linked with
      hypercoagulable states and thrombus formation. Although a number of infections
      have been associated with the transient production of anti-cardiolipin
      antibodies, the effect the antibodies may have in contributing to thrombus
      formation is not well understood. The occurrence of Bacteroides species infection
      with transient anti-cardiolipin antibody has not been previously reported.

PMID- 12811234
TI  - Transplant immunobiology: a crucial role for heparan sulfate glycosaminoglycans?

PMID- 12811235
TI  - Short-term immunosuppressive treatment of the donor ameliorates consequences of
      ischemia/ reperfusion injury and long-term graft function in renal allografts
      from older donors.
AB  - BACKGROUND: Grafts from so-called "marginal donors" are increasingly used for
      organ transplantation. The combination of reduced organ quality and additional
      inflammatory damages may be particularly detrimental in these grafts. In a
      previous study, we showed the beneficial effects on long-term graft outcome of
      "suboptimal" grafts by the induction of heme oxygenase-1. Here we tested the
      impact of short-term donor treatment with established immunosuppressants.
      METHODS: Twelve-month-old Fischer 344 donor rats either were treated with
      prednisolone, mycophenolate mofetil, RAD, or FK506 24 hr and 1 hr before organ
      harvesting or remained untreated. Renal allografts were perfused with University
      of Wisconsin solution and kept at 4 degrees C for an ischemic period of 2 hr.
      Morphologic, immunohistologic, and real time reverse transcriptase-polymerase
      chain reaction analyses for relevant markers were performed at serial intervals
      and at the end of the observation period (6 months). RESULTS: All animals
      survived the observation period, although the ischemic time resulted in
      accelerated chronic graft dysfunction. Grafts from donors treated with
      prednisolone or FK506 demonstrated significantly improved graft function and
      structure by 6 months. Mononuclear infiltrates were significantly reduced by the
      end of the observation period, whereas intragraft mRNA levels of tumor necrosis
      factor-alpha and interleukin-10 were significantly altered during the early
      period after transplantation. Minor improvements in graft function and histologic
      alterations of suboptimal grafts were observed after pretreatment with
      mycophenolate mofetil and RAD. CONCLUSION: Donor treatment with approved
      immunosuppressants, in particular prednisolone or FK506, represents a novel
      therapeutic strategy of clinical relevance, most importantly when using grafts
      from marginal donors.

PMID- 12811236
TI  - Functional and structural integrity of porcine pancreatic grafts subjected to a
      period of warm ischemia and cold preservation with histidine-tryptophan
      ketoglutarate (custodiol) or University of Wisconsin solution.
AB  - BACKGROUND: University of Wisconsin (UW) solution (Viaspan) is currently used to
      preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate
      (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas
      preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia
      (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was
      assessed after various periods of WI and compared with grafts flushed and
      preserved with UW solution. METHODS: A total of 14 pigs were used: G1 (n=4, UW)
      and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4
      (n=3, HTK) with 30-min WI and 16-hr cold storage. RESULTS: All animals in G1 and
      G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and
      G4. HTK perfusion was associated with increased wet weight. Transient
      hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range:
      8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced
      in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical
      pancreatitis as compared with UW-stored grafts on the first postoperative day in
      the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on
      postoperative day 14 were similar in both groups. Vascular congestion was
      uniformly observed and was considered a typical feature of WI. CONCLUSIONS:
      Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this
      experimental nonheartbeating donor model. HTK solution seems to provide reliable
      graft function in this setting and to be equivalent to UW.

PMID- 12811237
TI  - Spleen transplantation in miniature swine: surgical technique and results in
      major histocompatibility complex-matched donor and recipient pairs.
AB  - BACKGROUND: Spleen transplantation (Tx) between some strains of rodents can lead
      to donor-specific tolerance either spontaneously or after a short course of
      immunosuppression. This study developed a surgical technique for spleen Tx in
      miniature swine to investigate its immunologic impact in a large animal model.
      METHODS: The preferred surgical technique of spleen Tx (n=8) involved excision of
      the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel
      patches of donor aorta and portal vein were anastomosed to the abdominal aorta
      and inferior vena cava, respectively, of the (splenectomized) recipient. The
      results in four major histocompatibility complex-matched pairs that were
      mismatched for the porcine allelic antigen are reported. Two recipients were
      untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one
      received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was
      followed by fluorescence-activated cell sorter, and graft survival was assessed
      by histology. RESULTS: Spleen Tx was technically successful. In two untreated
      pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and
      lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic
      rejection by day 28. In two treated pigs, chimerism was present in the blood for
      47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days,
      respectively. CONCLUSION: Spleen Tx in major histocompatibility complex-matched
      pairs treated with CsA+/-thymic irradiation results in prolonged chimerism and is
      associated with the development of in vivo unresponsiveness to the transplanted
      spleen.

PMID- 12811238
TI  - Suppressed complement activation in human decay accelerating factor transgenic
      porcine liver cross-circulated with nonhuman primates.
AB  - BACKGROUND: We developed an extracorporeal liver perfusion (ECLP) system as a
      liver-assist device. In this study, we evaluated the safety of the ECLP using
      human decay accelerating factor (hDAF) transgenic porcine livers in healthy
      baboons. METHODS: Livers were isolated from five hDAF transgenic pigs and five
      nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and
      healthy baboons were performed without immunosuppressive agents. Cross
      circulation was discontinued in any of the following circumstances: elevated
      hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive
      exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24
      hr well-conditioned cross-circulation. RESULTS: The cross-circulations with
      nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard
      deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three
      cross-circulations with hDAF transgenic porcine livers were performed for 24 hr;
      the other two cross-circulations were discontinued at 13 and 17 hr because of
      massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1
      hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver
      was less than that in the nontransgenic liver, although immunoglobulin-M
      deposition was comparable. The porcine livers showed no apparent interlobular
      bleeding or lobular necrosis. All porcine livers maintained bile production
      during the cross-circulation. No baboons showed any serious complications after
      the cross-circulation. CONCLUSION: The hDAF transgenic porcine liver reduced
      complement activation in xenoperfusion with healthy nonhuman primate blood and
      led to extended duration of cross-circulation.

PMID- 12811239
TI  - Long-term islet allograft survival in nonobese diabetic mice treated with
      tacrolimus, rapamycin, and anti-interleukin-2 antibody.
AB  - BACKGROUND: Nonobese diabetic (NOD) mice develop autoimmune diabetes with
      features similar to those observed in the human disease. The concurrence of
      allorecognition and recurrence of autoimmunity might explain why most of the
      treatments successful in preventing islet allograft destruction in other
      nonautoimmune combinations often fail in NOD recipients. To assess the value of
      the NOD mouse model for the evaluation of treatments relevant to clinical islet
      transplantation, the authors have tested the effect of a protocol closely
      resembling the one successfully used in the Edmonton clinical trial on the
      survival of islet allografts in NOD mice. METHODS: C57BL/6 islets were
      transplanted under the kidney capsule of spontaneously diabetic NOD mice.
      Treatment consisted of a combination of rapamycin, tacrolimus, and anti
      interleukin (IL)-2 monoclonal antibody. Control groups received each treatment
      alone, a combination of two agents, or no treatment. RESULTS: Untreated animals
      invariably lost their graft within 13 days. Administration of rapamycin and
      tacrolimus significantly prolonged graft survival, with two of seven animals
      bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody
      therapy further improved graft survival, with six of eight grafts functioning
      longer than 100 days and two of eight grafts functioning longer than 200 days.
      CONCLUSIONS: In view of the limited success obtained with other treatments in
      this model, the dramatic prolongation of graft survival observed in the authors'
      study, by using a therapy that mimics one successfully used in clinical trials,
      seems to validate the NOD mouse as a meaningful model for the study of
      therapeutic interventions for the prevention of islet graft loss.

PMID- 12811240
TI  - Full reconstitution of hematopoietic system by murine umbilical cord blood.
AB  - BACKGROUND: Murine umbilical cord blood cells (UCBCs) were studied for their
      ability to reconstitute the hematopoietic system. METHODS: On average, 150 microL
      of cord blood per fetus containing 1.2 to 2 x 10(4) nucleated cells were
      collected from day 18.5 fetal umbilical cord, and 3 to 6 x 10(3) cells per fetus
      were obtained after separation by gradient centrifugation. RESULTS: Although
      lineage marker-, c-Kit+, and Sca-1+ cells were detectable among UCBCs, cells
      designated to be in the side population (SP) by Hoechst 33342 staining were
      hardly detectable within this population; the frequency of cells of this
      phenotype was less than 1 of 105. Instead, the lineage marker-, c-Kit+, and Sca-1
      population contained a considerable number of SP cells. Nevertheless, UCBCs
      obtained from fetuses of green fluorescent protein-transgenic mice successfully
      reconstituted the blood cells of lethally irradiated recipients. Fluorescent
      cells could be readily detected in every blood cell lineage and among immature
      cell populations. Furthermore, fluorescent SP cells sorted from the recipient
      bone marrow cells could also reconstitute the blood cells in the secondary
      recipients, indicating that UCBCs also replenished bone marrow stem cells.
      CONCLUSION: Murine UCBC could fully reconstitute the hematopoietic system of
      lethally irradiated recipients including hematopoietic stem cells in bone marrow.

PMID- 12811241
TI  - Heterotopic auxiliary liver in an isolated and vascularized segment of the small
      intestine in rats.
AB  - BACKGROUND: Development of an auxiliary liver is of interest for treating several
      conditions. To examine whether an isolated intestinal segment will support
      development of a heterotopic auxiliary liver, we studied the fate of liver
      microfragments in rats. METHODS: Small intestinal segments with intact
      circulation were created, and the small intestinal mucosa was removed. The
      intestinal segments were filled with autologous liver microfragments, and animals
      were studied for various periods. RESULTS: Initially, liver microfragments were
      engulfed by a serosanguineous exudate enriched in polymorphonuclear leukocytes,
      suggesting an early granulation-type response. Transplanted liver fragments were
      subsequently reorganized and showed morphologic integrity with typical hepatic
      lobular organization. Transplanted tissue contained healthy hepatocytes with
      abundant glycogen content. Transplanted liver remained intact in the small
      intestine for up to 40 days, although at later times portal fibrosis and bile
      ductular proliferation were apparent, despite the absence of cholestasis or
      hepatocellular abnormalities. In contrast, instillation of liver microfragments
      in the peritoneal cavity led to rapid loss of tissue integrity and phagocytotic
      clearance of transplanted tissue. CONCLUSIONS: Small intestinal segments denuded
      of the mucosal layer can support heterotopically transplanted liver. Further
      development of this auxiliary liver system will provide insights into mechanisms
      concerning neo-organogenesis and into potential therapeutic applications of
      heterotopic liver in specific diseases.

PMID- 12811242
TI  - Despite efficient intrathymic negative selection of host-reactive T cells,
      autoimmune disease may develop in porcine thymus-grafted athymic mice: evidence
      for failure of regulatory mechanisms suppressing autoimmunity.
AB  - BACKGROUND: CD4 T-cell reconstitution and xenogeneic tolerance is achieved in T
      cell-depleted, thymectomized C57BL/6 (B6) mice and nude mice by grafting of fetal
      pig thymus (FP THY). Sixty percent of grafted nude mice and 10% of grafted
      thymectomized B6 mice develop a clinical illness resembling chronic graft-versus
      host disease. METHODS: Negative selection of mouse T cells in FP THY grafts was
      studied in "AND" TCR transgenic mice with a negative selecting MHC. Pathologic
      and immunohistochemical examinations and adoptive transfer assays were performed
      to determine the role of mouse CD4+ cells in the occurrence of autoimmune disease
      in this model. RESULTS: Marked clonal deletion of mouse thymocytes bearing a
      transgenic TCR ("AND"), which recognizes H2s expressed by host hematopoietic
      cells, was observed in FP THY grafts. Pathologic and immunohistochemical
      examinations of the liver, skin, lungs, and kidneys of mice with wasting syndrome
      showed marked mouse CD4+ T-cell infiltration without detectable pig cells. After
      adoptive transfer of splenocytes, but not of CD4+ cell-depleted splenocytes, from
      sick mice along with B6 bone marrow cells to lethally irradiated syngeneic B6
      mice, the secondary recipients developed a similar autoimmune syndrome as the
      donors. Cotransfer of naive syngeneic splenocytes prevented the occurrence of
      autoimmune disease in secondary recipients of splenocytes from healthy FP THY
      grafted BALB/c nude mice. CONCLUSION: These results demonstrate a key role for
      mouse CD4+ T cells in causing autoimmune disease in this model and suggest the
      importance of regulatory mechanisms in addition to intrathymic clonal deletion
      for the maintenance of tolerance to recipient antigens.

PMID- 12811243
TI  - Porcine cytomegalovirus and coagulopathy in pig-to-primate xenotransplantation.
AB  - BACKGROUND: A rapidly progressive disorder termed consumptive coagulopathy (CC)
      has been observed frequently in pig-to-baboon renal xenotransplantation. CC may
      be initiated by endothelial activation and induction of procoagulant factors
      after immunologic injury or infection, or by molecular incompatibilities between
      porcine coagulation proteins and primate clotting factors. The activation of
      porcine (P) cytomegalovirus (PCMV) and baboon (B) CMV infections has been
      documented in pig-to-primate xenotransplantation. The purpose of this study was
      to determine the contribution of PCMV and BCMV to CC. METHODS: Endothelial
      activation was assessed by means of measurement of porcine tissue factor (pTF) in
      a functional assay in primary porcine aortic endothelial cells (PAEC) in vitro.
      Renal xenografts and native kidneys were studied by immunohistochemistry in
      immunosuppressed swine and baboons. BCMV and PCMV DNA was measured by
      quantitative molecular assays using real-time polymerase chain reaction. RESULTS:
      In vitro, infection of PAEC with PCMV resulted in a significant increase of pTF
      expression. In vivo, pTF increase occurred without the activation of PCMV in two
      xenografts, and in four grafts no pTF was detected despite PCMV activation. All
      animals with graft pTF increase developed CC. BCMV activation in the baboon
      xenograft recipients did not correlate with CC or pTF increase. Control pigs and
      baboons had activation of PCMV and BCMV, respectively, but without coagulation
      abnormalities. CONCLUSIONS: PCMV induces endothelial cell activation in vitro
      with procoagulant expression. However, in vivo, CC and pTF induction has an
      uncertain relationship to increased replication of PCMV within a xenograft.
      Although the data do not exclude a contributory role of PCMV in CC, other
      mechanisms are also likely to contribute to coagulopathies observed in pig-to
      primate xenotransplantation.

PMID- 12811244
TI  - Prognostic significance of microvascular thrombosis in donor kidney allograft
      biopsies.
AB  - BACKGROUND: With a continuing demand for donor kidneys for organ transplantation,
      it is important to understand the significance of pathologic findings in the
      donor organ before transplantation. Microvascular thrombosis is sometimes
      encountered in association with disseminated intravascular coagulation in the
      donor, and it is unclear whether this finding may affect immediate allograft
      function and long-term graft survival. To further elucidate this question, we
      examined our experience with microvascular thrombosis in donor biopsies in the
      kidney transplant program at our institution. METHODS: Donor kidney biopsies
      showing microvascular thrombosis were identified from consecutive donor biopsies
      in the Duke University Medical Center transplant file database between January 1,
      1995 and December 31, 2000. These biopsies and all other kidney biopsies and
      specimens from the recipients of these kidneys thus identified were reviewed.
      Sections were stained using a variety of methods, including hematoxylin-eosin,
      periodic acid-Schiff, methenamine silver, and Masson trichrome methods. Clinical
      records of the transplant recipients of these kidneys were also reviewed to
      assess allograft performance and survival. RESULTS: From 230 consecutive donor
      kidney biopsies, we identified eight cases exhibiting donor-microvascular
      thrombosis. Mean follow-up times were 27.5 months for the thrombi group and 35
      months for the non-thrombi group. Recipients of grafts with donor thrombi were
      more likely to exhibit delayed graft function, but graft function at 1 and 2
      years and graft survival were similar between the two groups. Subsequent
      posttransplantation biopsies in five of eight cases showed no evidence of
      residual thrombosis. CONCLUSIONS: These data suggest that the presence of donor
      microvascular thrombosis does not portend poor outcome in renal transplantation.

PMID- 12811245
TI  - Cytomegalovirus infection and development of biliary complications after liver
      transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is known to cause ulceration and
      mucosal hemorrhage in the gastrointestinal tract. Gastroduodenal and biliary
      complications were prospectively evaluated in 100 consecutive liver transplant
      patients in whom CMV was monitored during the first posttransplant year. METHOD:
      Gastroduodenal biopsy specimens were taken from 36 patients by endoscopies and in
      28 patients by endoscopic retrograde cholangiopancreatography, and bile duct
      specimens were taken from three patients who underwent surgical reconstruction
      because of biliary complication. CMV was demonstrated from blood by the pp65
      antigenemia test and from frozen sections of tissue specimens by
      immunohistochemistry and in situ hybridization. RESULTS: Symptomatic CMV
      infection, treated with ganciclovir, developed in 49 recipients: 13 (100%) of CMV
      seropositive donor (D+) seronegative recipient (R-) cases, 29 (45%) D+/R+ cases,
      and 7 (32%) D-/R+ cases. Duodenal ulcer developed in three and hemorrhagic
      gastritis in three recipients. CMV antigens were found from the gastroduodenal
      mucosa in 37 (69%) of the 54 studied recipients. The biliary complication rate
      was 24%. Preceding or concomitant CMV antigenemia was demonstrated in 75% of
      patients with a biliary complication (68% in CMV D+/R+ or D-/R+ and 100% in D+/R-
      recipients). The biliary complication rate was higher among recipients with CMV
      antigenemia, compared with recipients without (P<0.05). CMV antigenemia, CMV
      infection, or both in the duodenal mucosa was found in 96% of patients with a
      biliary complication. In two patients who underwent surgical reconstruction, CMV
      antigens and DNA were demonstrated in the bile ducts. CONCLUSIONS: Liver
      transplant patients are at risk of developing biliary complications after CMV
      infection, especially those with primary CMV infection.

PMID- 12811246
TI  - The impact of cytomegalovirus infections and acute rejection episodes on the
      development of vascular changes in 6-month protocol biopsy specimens of cadaveric
      kidney allograft recipients.
AB  - BACKGROUND: The role of cytomegalovirus (CMV) in chronic kidney allograft
      rejection remains controversial. The purpose of this study was to examine the
      impact of CMV infection on histopathologic changes in 6-month protocol biopsy
      specimens of kidney allografts. METHODS: Altogether, 52 renal allograft
      recipients were studied. CMV infection was diagnosed by CMV antigenemia test,
      viral cultures from blood and urine, or both. CMV was demonstrated in the biopsy
      specimens by antigen detection and hybridization in situ. Acute rejections were
      diagnosed by biopsy histology, and biopsy specimens were graded according to the
      Banff '97 classification. RESULTS: CMV infection was diagnosed in 41 patients.
      The 11 patients in whom CMV infection was not detected were used as controls.
      Acute rejection was diagnosed in 22 of 41 CMV patients and in 6 of 11 control
      patients. CMV was demonstrated in the biopsy specimens of 19 of 41 CMV patients.
      CMV was not associated with increased glomerular, tubular, or interstitial
      changes. However, the arteriosclerotic changes in small arterioles were
      significantly increased in the subgroup of patients where CMV was demonstrated in
      the graft as compared with controls (P<0.01). Analysis of the impact of acute
      rejection on arteriolar thickening showed that only a positive history of both
      acute rejection and CMV found in the graft was associated with significantly
      increased vascular changes compared with CMV-free recipients (P<0.05).
      CONCLUSIONS: Neither CMV nor acute rejection alone was associated with increased
      vascular or other histopathologic changes in 6-month protocol biopsy specimens of
      kidney allografts, but a previous history of both acute rejection and the
      presence of CMV in the graft was associated with increased vascular changes.

PMID- 12811247
TI  - Suppression of early T-cell-receptor-triggered cellular activation by the Janus
      kinase 3 inhibitor WHI-P-154.
AB  - BACKGROUND: Therapeutic targeting of Janus kinase 3 (JAK3) has received
      particular attention, because it is associated with the common gamma signaling of
      cytokine receptors and thus vitally influences T-cell growth and survival. Recent
      evidence, however, indicates a critical role for JAK3 in signaling linked to the
      T-cell antigen receptor. METHODS: In this study we investigated whether targeting
      JAK3 with a rationally designed inhibitor affects early T-cell activation events.
      T cells were stimulated by CD3 and CD28 cross-linking, and interleukin (IL)-2
      production, activation marker expression, increase of free intracellular Ca2+
      concentration, activation of the extracellular-related kinase, and nuclear
      translocation of transcription factors were evaluated. RESULTS: We found that
      JAK3 inhibitor treatment dramatically impaired T-cell-receptor (TCR)-induced IL-2
      production, surface activation marker expression (CD69, CD154), and homotypic T
      cell aggregation. Accordingly, mRNA production of IL-2, interferon-gamma, and IL
      10 was profoundly inhibited. Molecular analysis revealed that TCR-triggered
      phosphorylation of phospholipase C-gamma1, increase in cytoplasmic Ca2+
      concentration, and activation of extracellular-related kinase were markedly
      reduced by the JAK3 inhibitor, resulting in substantially decreased DNA binding
      of nuclear factor of activated T cells and alkaline phosphatase-1 and subsequent
      IL-2 promoter activation. Remarkably, on TCR-independent stimulation, IL-2
      production, CD69 expression, and blast formation were completely insensitive to
      JAK3 inhibitor treatment. CONCLUSION: These data indicate that pharmacologic
      targeting of JAK3 uncouples early TCR-triggered signaling from essential
      downstream events, which may have important implications for the use of such
      compounds in T-cell-mediated disorders such as allograft rejection or graft
      versus-host disease.

PMID- 12811248
TI  - Establishment of immortalized human hepatic stellate scavenger cells to develop
      bioartificial livers.
AB  - BACKGROUND: Maintenance of liver-specific functions has been shown to be
      stabilized by co-cultivation of hepatocytes with hepatic stellate cells (HSC).
      Because the limited lifespan of human HSC is a major hurdle to their use, the
      authors report here the amplification of human HSC populations in vitro by
      retroviral transfer of human telomerase reverse transcriptase (hTERT). METHODS:
      Human HSC strain LI 90 cells were transduced with a retroviral vector SSR#197
      expressing hTERT and green fluorescent protein (GFP) cDNA flanked by a pair of
      loxP. TWNT-1, one of SSR#197-immortalized HSC, was characterized. Differentiated
      liver functions were evaluated in an immortalized human hepatocyte NKNT-3-TWNT-1
      co-culture system. RESULTS: TWNT-1 cells showed differential functions of HSC,
      including uptake of acetylated low-density lipoproteins and synthesis of collagen
      type I and hepatocyte growth factor. Efficient excision of the retrovirally
      transferred hTERT and GFP cDNAs was achieved by TAT-mediated expression of the
      Cre recombinase and subsequent GFP-negative cell sorting. When co-cultured with
      TWNT-1 cells, NKNT-3 increased protein expression of the detoxifying cytochrome
      P450-associated protein isoenzymes 3A4 and 2C9 and urea synthesis. CONCLUSIONS:
      TWNT-1 cells could be valuable in the study of integrated liver functions and
      contribute to the optimization of liver cell therapies and bioartificial livers.

PMID- 12811249
TI  - Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506)
      in prevention of acute heart and kidney allograft rejection and reversal of
      ongoing heart allograft rejection in the rat.
AB  - BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778
      and FK779) monotherapy and combination therapy were examined in prevention of
      acute heart and kidney allograft rejection and reversal of ongoing acute heart
      allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and
      ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and
      kidney transplantation models. Immunosuppressants were administered orally from
      day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after
      transplantation for the reversal of ongoing acute rejection. RESULTS: In the
      prevention of acute heart rejection model, recipient rats treated with
      monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related
      prolongation of mean survival time (MST) compared with naive control rats
      (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and
      FK778 indicated that an additive to synergistic interaction was produced when
      compared with the respective monotherapies (combination index [CI]=0.631-1.022).
      These results were reproducible with tacrolimus and FK779 combination therapy
      (CI=0.572-0.846). Furthermore, similar results were also found in the prevention
      of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal
      of ongoing acute heart allograft rejection, combination therapy of tacrolimus and
      FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared
      with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of
      tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of
      acute heart and kidney rejection and reversal of ongoing heart allograft
      rejection in the rat.

PMID- 12811250
TI  - The functional roles of porcine CD80 molecule and its ability to stimulate and
      regulate human anti-pig cellular response.
AB  - BACKGROUND: The pig is currently considered to be the most likely candidate for a
      xenogenic-organ source. Anti-pig human T-cell response via co-stimulatory
      molecules has been studied with great interest. The soluble form of porcine CD80
      has recently been cloned and characterized, but the sequence of the transmembrane
      form has not been determined. The purpose of this study was to investigate the
      functional interaction between porcine CD80 and human T cells using the full
      length clone of porcine CD80. MATERIALS AND METHODS: Specific complementary DNA
      (cDNA) clones encoding porcine CD80 were isolated and sequenced using rapid
      amplification of cDNA ends-polymerase chain reaction. Polymerase chain reaction
      amplified cDNA coding for the open reading frame of the porcine CD80
      transmembrane form was subcloned into an expression vector and then transfected
      into Chinese hamster ovary (CHO) cells. CHO cells transfected with porcine CD80
      (CHO-pCD80) were co-cultured with human CD4+ T cells and then interleukin-2
      secretion was measured and transferred pCD80 expression in these human T cells
      was detected by flow cytometry. RESULTS: We cloned and determined the complete
      nucleotide sequence for the transmembrane form of porcine CD80. Results from our
      T-cell co-stimulatory assay showed significant interleukin-2 production when co
      stimulated with CHO-pCD80. Human naive CD4+ T cells acquired xenogenic pCD80
      molecules in the process of T-cell activation. CONCLUSIONS: Findings from this
      study seem to suggest that pCD80 has the functional ability to regulate human
      anti-pig cellular response. In addition, genetic manipulation of porcine co
      stimulatory molecules offers a potentially new therapeutic strategy to prevent
      xenogeneic rejection across species.

PMID- 12811251
TI  - Comparative study of allograft survival of heterotopic and orthotopic small bowel
      transplantation in rat.
AB  - BACKGROUND: Small bowel allografts can either be placed heterotopically or
      orthotopically. In heterotopic small bowel transplantation (H-SBT), the host
      small intestine containing a substantial amount of gut-associated lymphoid tissue
      is removed, whereas in conventional orthotopic small bowel transplantation (O
      SBT) it is retained. This study compared the allograft survival of H-SBT and O
      SBT and evaluated the effect of retaining the host intestine in O-SBT in an
      altered O-SBT (AO-SBT) model. METHODS: SBT was performed in a high-responder rat
      stain combination (blood group D Agouti --> Lewis). Immunosuppressive treatment
      consisting of a short course of FK506 (2 mg/kg/day IM for 3 days before
      transplantation and 0.3 mg/kg/day for 14 days after transplantation) was used.
      RESULTS: Survival (mean +/- SD) of H-, O-, and AO-SBT untreated animals was
      6.25+/-0.58 days, 6.5+/-0.58 days, and 6.7+/-0.25 days, respectively. With FK506
      immunosuppression, survival of H-SBT animals was 49.3+/-13.17 days, whereas 75%
      (12/16) and 80% (4/5), respectively, of O-SBT and AO-SBT animals achieved
      indefinite survival (>120 days) with functioning grafts. CONCLUSION: Our data
      suggest that heterotopic placement of intestinal allografts results in a more
      severe graft rejection than orthotopic placement. The indefinite survival of O
      SBT is not due to of the removal of host intestine carrying a heavy load of gut
      associated lymphoid tissue.

PMID- 12811252
TI  - Disseminated encephalitozoon cuniculi infection in a Mexican kidney transplant
      recipient.
AB  - BACKGROUND: No cases of Encephalitozoon cuniculi infection have been reported in
      transplant patients. METHODS: A 42-year-old man received a renal transplant 8
      months earlier because of terminal glomerulonephritis and was admitted with
      cough, fever, diarrhea, abdominal pain, and colon wall thickening. While under
      rapamycin (2 g/day), cyclosporine A (4.4 mg/kg/day), and prednisone (100 mg/day)
      therapy, he developed Banff grade IB graft rejection and was treated with
      methylprednisolone (1 g/day) for 3 days and oral prednisone (60 mg/d). RESULTS:
      Microbiologic studies were inconclusive, and biopsy specimens of ileum, colon,
      liver, and the grafted kidney revealed numerous gram-positive microsporidia
      spores. Parasitophorous vacuoles containing various developing stages of
      Encephalitozoon were seen. Immunofluorescence studies identified the etiologic
      agent as E. cuniculi. Albendazole therapy resulted in clinical improvement but no
      eradication after 10 months of follow-up. CONCLUSIONS: This report describes what
      is, to the authors' knowledge, the first case of disseminated E. cuniculi
      infection in a kidney transplant human immunodeficiency virus-negative patient
      from Mexico.

PMID- 12811253
TI  - Auxiliary partial orthotopic liver transplantation for fulminant hepatitis:
      regeneration of the diseased native liver in a pig model.
AB  - BACKGROUND: This study was performed to develop a clinically relevant porcine
      model of auxiliary partial orthotopic liver transplantation (APOLT) for fulminant
      hepatic failure. METHODS: FHF was induced by intraportal administration of alpha
      amanitin and lipopolysaccharide. Thereafter, pigs were divided into four groups.
      Group 1 was an untreated, control group. In group 2, pigs underwent only a left
      hemihepatectomy. Pigs in groups 3 and 4 received APOLT after hemihepatectomy.
      Tacrolimus was administered to pigs in group 4, but not to those in group 3.
      RESULTS: Two-week survival rates were 0%, 20%, 40%, and 100% for groups 1, 2, 3,
      and 4, respectively. In group 4, after abolishing the graft function at 1 week,
      pigs survived for more than 2 weeks, and regeneration of the native liver was
      confirmed histologically. CONCLUSIONS: Pigs suffering from fulminant hepatic
      failure could achieve long survival and liver regeneration with a temporary
      support of the auxiliary graft.

PMID- 12811254
TI  - Red blood cell alloantibodies and liver transplantation in Chinese patients.
AB  - Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients
      of liver transplants and can cause severe delayed hemolysis. A retrospective
      survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese
      recipients of liver transplants, compared with a 3.7% background hospital
      incidence. The spectrum of RBC alloantibodies was different from that in white
      recipients, with no anti-D or anti-K antibodies but with a significant incidence
      of anti-Mi (29%) antibodies. There was significantly increased transfusion in RBC
      alloantibody positive cases. Delayed hemolysis also resulted in higher day-7
      bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five
      RBC alloantibody cases, including three early deaths. Seven cases in the RBC
      alloantibody negative group, but none in the positive group, were salvaged by
      regraft. Blood banks servicing transplant centers should be aware of ethnic
      patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival
      as a result of difficult postoperative stabilization, especially in cases
      requiring massive transfusion.

PMID- 12811256
TI  - Effect of antithymocyte globulin on quantitative immune recovery and graft-versus
      host disease after partially T-cell-depleted bone marrow transplantation: a
      comparison between recipients of matched related and matched unrelated donor
      grafts.
AB  - The effect of antithymocyte globulin (ATG) on quantitative immune recovery and
      graft-versus-host disease (GVHD) after partially T-cell-depleted bone marrow
      transplantation was analyzed in 59 and 32 recipients of grafts from matched
      related donors and matched unrelated donors (MUDs), respectively. The
      conditioning regimen was similar in all patients, except for ATG which was given
      only to MUD recipients. Thirteen MUD patients were treated with high-dose (20
      mg/kg) ATG and 19 with low-dose (8 mg/kg) ATG. During the posttransplant period,
      CD3+, CD4+, and CD8+ T-cell numbers and the incidence of acute and chronic GVHD
      were significantly lower in MUD recipients compared with matched related donor
      recipients. MUD recipients treated with high-dose ATG showed the worst T-cell and
      subsets recovery. These data indicate that ATG, often used as part of
      conditioning regimens in recipients of T-cell-depleted grafts from MUDs,
      contributes to the severe and prolonged T-cell deficiency that is typical of
      these patients. On the other hand, it effectively reduces the incidence and
      severity of GVHD.

PMID- 12811255
TI  - Kidney transplantation improves endothelium-dependent vasodilation in patients
      with endstage renal disease.
AB  - Kidney transplantation (Tx) improves the cardiovascular outcome of patients
      receiving hemodialysis (HD). Therefore, we asked whether Tx improves the
      endothelial dysfunction of HD patients. Eight patients were studied twice: (1)
      during HD and (2) after Tx. We also studied eight matched control subjects. We
      measured forearm blood flow by venous occlusion plethysmography. We administered
      intrabrachial infusions of three doses of norepinephrine, glycerol trinitrate,
      acetylcholine (ACH), and N-monomethyl-L-arginine. The response to ACH was reduced
      in HD patients compared with controls (P<0.001). The response to ACH in HD
      patients improved after Tx, and this change was significant for low-dose ACH
      (P<0.05 for dose one and two compared with HD). The response to glycerol
      trinitrate, which was reduced in HD patients compared with controls (P<0.01),
      remained unchanged after Tx. N-monomethyl-L-arginine and norepinephrine
      comparably reduced forearm blood flow in all groups. This is the first evidence
      showing an improvement of endothelial dysfunction in HD patients after Tx.

PMID- 12811257
TI  - Pulmonary actinomycosis in solid organ transplantation.

PMID- 12811258
TI  - Ureteral obstruction in a transplanted kidney secondary to a subserous myoma
      uteri.

PMID- 12811259
TI  - Successful hand transplantation or too early to tell?

PMID- 12811260
TI  - Patient management by cyclosporine C2 monitoring: not enough science yet to
      justify the practice.

PMID- 12811261
TI  - Cytomegalovirus cholecystitis: a case report.

PMID- 12811262
TI  - Cochrane back review group.

PMID- 12811263
TI  - A prospective, randomized, controlled cervical fusion study using recombinant
      human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the
      ATLANTIS anterior cervical plate.
AB  - STUDY DESIGN: A prospective, randomized, pilot clinical trial compared
      recombinant human bone morphogenetic protein-2 (rhBMP-2) with iliac crest
      autograft bone for the treatment of human cervical disc disease. OBJECTIVE: To
      examine the safety and effectiveness of using INFUSE Bone Graft (rhBMP-2 applied
      to an absorbable collagen sponge), as compared with an autogenous iliac crest
      bone graft placed inside the CORNERSTONE-SR fibular allograft, in anterior
      cervical discectomy and interbody fusion. SUMMARY OF BACKGROUND DATA: Recombinant
      human bone morphogenetic protein-2 is an osteoinductive protein that induces a
      reliable fusion in the lumbar spine, but it has not been studied in patients with
      degenerative cervical disc disease. METHODS: For this study, 33 patients with
      degenerative cervical disc disease were randomly assigned to investigational or
      control groups. The investigational group received a fibular allograft
      (CORNERSTONE-SR Allograft Ring) with an rhBMP-2-laden collagen carrier inside the
      graft along with an ATLANTIS anterior cervical plate. The control group received
      a fibular allograft with cancellous iliac crest autograft placed inside it, along
      with an ATLANTIS anterior cervical plate. The patients underwent plain
      radiographs at 6 weeks, then at 3, 6, 12, and 24 months, and CT scans at 3 and 6
      months after surgery. They also completed general health profiles and self
      evaluation scales. Adverse events were evaluated for severity, duration,
      association with the implant, and the need for a second surgical procedure.
      RESULTS: All the patients evaluated had solid fusions 6, 12, and 24 months after
      surgery. There were no device-related adverse events. At 24 months, the
      investigational group had mean improvement superior to that of the control group
      in neck disability and arm pain scores (P < 0.03 each). CONCLUSIONS: This pilot
      study demonstrates the feasibility of using rhBMP-2 safely and effectively in the
      cervical spine.

PMID- 12811265
TI  - A biomechanical comparison of facet screw fixation and pedicle screw fixation:
      effects of short-term and long-term repetitive cycling.
AB  - STUDY DESIGN: A biomechanical study was conducted to assess the stabilization
      performance of transfacet pedicle screw fixation. OBJECTIVE: To compare the
      biomechanical effects of short-term and long-term cyclic loading on lumbar motion
      segments instrumented with either a pedicle screw or a transfacet pedicle screw
      construct. SUMMARY OF BACKGROUND DATA: Facet screw fixation is an alternative to
      pedicle screw fixation that permits the use of a minimally invasive strategy. It
      is not known whether facet screw fixation can provide stability equivalent to
      pedicle screw fixation during cyclical loading. Therefore, transfacet pedicle
      screw fixation and standard pedicle screw fixation techniques were compared
      biomechanically. METHODS: Lumbar motion segments were tested under short-term and
      long-term cyclic loading conditions. For the short-term phase, specimens were
      tested intact for six cycles (to 400 N or 4 Nm) in compression, flexion,
      extension, lateral bending, and torsion. The specimens then were instrumented
      with bilateral semicircular interbody spacers and pedicle screw instrumentation
      or transfacet pedicle screws, and the testing sequence was repeated. For the long
      term phase, 12 specimens were instrumented in a similar manner and loaded to 6 Nm
      of flexion bending for 180,000 cycles. RESULTS: For the short-term phase, both
      fixation systems had significantly greater stiffness and reduced range of motion,
      as compared with the intact state. No differences were observed between the
      fixation systems except in flexion, wherein transfacet pedicle screw specimens
      were significantly stiffer than traditional pedicle screw specimens. For the long
      term phase, the stiffness and range of motion did not significantly increase or
      decrease over repetitive cycling of the instrumented specimens. Furthermore, no
      significant difference between the fixation systems was observed. CONCLUSIONS:
      The stability provided by both transfacet pedicle screw fixation and traditional
      pedicle screw fixation was not compromised after repetitive cycling. In this
      model, transfacet pedicle screw fixation appears equivalent biomechanically to
      traditional pedicle screw fixation.

PMID- 12811266
TI  - Biomechanics and electromyography of a common idiopathic low back disorder.
AB  - STUDY DESIGN: In vivo feline preparation groups loaded into lumbar flexion at
      different magnitudes and an unloaded control group. OBJECTIVE: To demonstrate
      that a static, constant load flexion of the lumbar spine results in a complex
      neuromuscular disorder. SUMMARY OF BACKGROUND DATA: Epidemiology suggests that
      static lumbar flexion is a cause of low back disorders. There is little direct
      experimental evidence describing the physiologic and biomechanical processes that
      elicit the disorder. Recent evidence shows that static flexion of the spine under
      constant displacement results in muscular spasms and a prolonged recovery period.
      The response of the spine to flexion under constant load of various magnitudes
      (as opposed to constant displacement) is not known. It was hypothesized that
      static lumbar flexion under constant load may elicit creep in spinal ligaments,
      discs, etc., causing microdamage and development of a neuromuscular disorder.
      METHODS: The lumbar spine of the feline was subjected to 20 minutes of constant
      load static flexion at physiologic load intensities from light to heavy while
      creep of lumbar viscoelastic tissues and EMG from the multifidus muscles of L3-L4
      to L5-L6 were recorded. Recordings were continued over a 7-hour rest period after
      the static flexion was terminated. RESULTS: Spasms and decreasing reflexive EMG
      were evident during the loading period, and a transient surge of EMG activity
      occurred at the beginning of the rest period. A second surge of EMG activity was
      seen 3-4 hours later. The four components of the neuromuscular disorder were
      present regardless of the load magnitude. A model was developed to quantify the
      disorder. CONCLUSION: A four-component neuromuscular disorder was elicited by a
      20-minute constant load static flexion even when very light loads were applied.
      The disorder was elicited by creep of the viscoelastic tissues, which resulted in
      spasms and muscular hyperexcitability lasting for >24 hours. Although the
      disorder was transient, the physiologic and biomechanical principles associated
      with its development could also explain cumulative trauma disorders.

PMID- 12811267
TI  - A reassessment of normal cervical range of motion.
AB  - STUDY DESIGN: Intraexaminer and interexaminer/procedure reliability and error
      analysis using a repeated-measures design. OBJECTIVE: To quantify sources of
      discrepancies in cervical range of motion values between two procedures that use
      the same potentiometric technology. SUMMARY OF BACKGROUND DATA: Studies using an
      early version of an electrogoniometer system, which was connected between a
      helmet worn by the study participant and a chair on which they sat, reported
      unusually high values for active and passive cervical range of motion, although
      measurements were reliable. To understand the sources of the discrepancies
      between that study and later studies (using upgraded software), the current study
      was designed to quantify possible sources of error contributed by various
      components of the procedures: helmet, thoracic reference, chair, and software.
      METHODS: A total of 22 asymptomatic study participants were evaluated in two
      separate sessions, 1-3 days apart. Components of two procedures were changed
      systematically in a series of repeated measurements to provide concurrent
      reliability and to assess sources of error between the two procedures. RESULTS:
      The reliabilities of both procedures were generally high with no systematic
      trends, except for lower values for flexion-extension studies with Procedure 2.
      Procedure 2 also provided systematically greater range of motion values (2-8
      degrees ) than Procedure 1, except for flexion (half-cycle). The source of the
      greatest discrepancy between the two procedures was the software, when comparing
      the original with the updated versions. With regard to the instrumentation, the
      greatest source of variability was in the thoracic reference post; next was the
      helmet, and least significant was the type of seat used. A comparison of overall
      procedure discrepancies and summation of individual elements of the procedures
      accounted for virtually all of the observed error. CONCLUSION: The potentiometer
      based electrogoniometer is a reliable instrument for determining cervical range
      of motion. Measurements appear to be more valid when the thoracic reference point
      is physically attached to the study participant's body. The original software
      provided with the system appears to have contributed to systematic overestimation
      of ranges of motion, but current units provide measurements that are both
      reliable and valid.

PMID- 12811268
TI  - Local kyphosis reduces surgical outcomes of expansive open-door laminoplasty for
      cervical spondylotic myelopathy.
AB  - STUDY DESIGN: This retrospective study analyzed the effects of cervical alignment
      on surgical results of expansive laminoplasty (ELAP) for cervical spondylotic
      myelopathy (CSM). OBJECTIVE: To determine the limitation of posterior
      decompression by ELAP for CSM in the presence of local kyphosis. SUMMARY OF
      BACKGROUND DATA: Several studies have reported that cervical malalignment
      affected surgical outcomes of ELAP. However, there has been no report to
      demonstrate crucial determinants of surgical outcomes of ELAP for CSM in relation
      to cervical sagittal alignment. METHODS: The study group comprised 114 patients
      who underwent ELAP for CSM. All were followed up for more than 2 years. The
      Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy
      (full score, 17 points) was used to evaluate surgical outcomes for each patient 2
      years after surgery. Statistical analysis with multivariate logistic regression
      models was used to ascertain the risk factors affecting postoperative surgical
      outcomes. RESULTS: The average JOA scores were 9.9 points before surgery and 14
      points 2 years after surgery. The recovery rate was 60.2%. Statistical analysis
      showed that signal intensity change on MRI and local kyphosis were the most
      crucial risk factors for poor surgical outcomes. Calculated with the logistic
      regression model, the highest risk of poor recovery was local kyphosis exceeding
      13 degrees. CONCLUSIONS: The influence of cervical malalignment on neurologic
      recovery after ELAP for CSM was shown. When patients have local kyphosis
      exceeding 13 degrees, anterior decompression or posterior correction of kyphosis
      as well as ELAP should be considered. Expansive laminoplasty for CSM is best
      indicated for patients with local kyphosis less than 13 degrees.

PMID- 12811269
TI  - MRI measurements of the cervical spine and their correlation to Pavlov's ratio.
AB  - STUDY DESIGN: Pavlov's ratio from plain radiographs in patients with neck pain
      but no radicular symptoms was compared with the areas of the cervical spinal cord
      and cerebrospinal fluid column on magnetic resonance scans. SUMMARY OF BACKGROUND
      DATA: The area of the cervical canal or cord obviously depends on both the
      sagittal and transverse diameters. Although the pathology in stenosis of the
      cervical spine is mainly in the sagittal plane, narrowing only in the sagittal
      diameter may not indicate significant reduction in the area of the canal. The
      transverse area of the cord has been shown to correlate well with the pathologic
      changes of the cord in cervical myelopathy. We correlated Pavlov's ratio on the
      plain radiographs to the area of the cerebrospinal fluid column and the area of
      the cord on the magnetic resonance scan. METHODS: We examined the lateral
      radiographs and axial and sagittal T2-weighted magnetic resonance scans in the
      neutral position of the cervical spine (C4-C7) of 87 patients with 332 levels
      with neck pain but no radicular symptoms and normal magnetic resonance scans. On
      the magnetic resonance images, the sagittal diameters of the cerebrospinal fluid
      column and the cord were measured at the midvertebra level on T2 sagittal images
      from C4 to C7. From the T2 axial images, the area of the cord and the area of the
      cerebrospinal fluid column were measured at the same levels. RESULTS: The
      correlation between Pavlov's ratio and the area of cerebrospinal fluid column was
      moderate, with the highest value of 0.31 at C5. The sagittal diameter of the
      cerebrospinal fluid column showed variable correlation with the area of the
      cerebrospinal fluid column. The highest correlation was 0.68 between the sagittal
      diameter and the area of the cerebrospinal fluid column at C7. The correlation
      between Pavlov's ratio and the area of the cord is around zero, with the highest
      correlation of 0.21 at C4. The sagittal diameter of the cord showed a moderate
      correlation with the area of the cord. CONCLUSION: This study shows a poor
      correlation between Pavlov's ratio and the space available for the cord.
      Therefore, this ratio cannot be solely relied upon to predict the area changes in
      that plane of the cervical spinal canal.

PMID- 12811270
TI  - Functional outcome analysis including preoperative and postoperative SF-36 for
      surgically treated adult isthmic spondylolisthesis.
AB  - STUDY DESIGN: Prospective and retrospective outcome analysis following
      arthrodesis for adult isthmic spondylolisthesis in 31 patients. OBJECTIVE: To
      examine whether or not patients having such surgery have a functional improvement
      in their lives. SUMMARY OF BACKGROUND DATA: The literature is full of articles
      concerning adolescent spondylolisthesis, the union rate for adult
      spondylolisthesis, the ability to reduce deformities, and the outcome of surgery
      for degenerative spondylolisthesis, but very scant on the postoperative
      functional outcome of adults with isthmic spondylolisthesis. METHODS: Functional
      outcome was analyzed by both preoperative and postoperative SF-36 questionnaires
      and by four additional functional questionnaires at follow-up. RESULTS:
      Statistically significant improvement was seen in six of the eight SF-36 scales.
      Fifty-five percent of the patients scored in the normal range at follow-up
      compared with none before surgery. CONCLUSION: Significant functional improvement
      was seen following surgical arthrodesis of the painful segments in adults with
      isthmic spondylolisthesis (P = 0.001). This study further confirms that such
      surgery is appropriate for patients failing adequate nonoperative treatment.

PMID- 12811271
TI  - L5-S1 segment survivorship and clinical outcome analysis after L4-L5 isolated
      fusion.
AB  - STUDY DESIGN: A retrospective investigation of the L5-S1 motion segment after an
      isolated L4-L5 posterior lumbar fusion. OBJECTIVE: To determine the survivorship
      of the L5-S1 segment in patients undergoing L4-L5 fusion and to identify the
      correlation between radiographic degeneration and clinical outcome at this level.
      SUMMARY OF BACKGROUND DATA: There is current controversy regarding future
      degeneration of the L5-S1 segment following single-segment fusion at L4-L5. There
      are no long-term studies that look at L5-S1 after L4-L5 fusion to assess the rate
      of degeneration at this adjacent segment and the functional clinical outcome of
      the patient. METHODS: Thirty-two consecutive patients (average age 56.4 years,
      range 27-77 years) having isolated L4-L5 posterior spinal fusion for instability
      or stenosis by a single surgeon were included in this study. There were 25
      females and 7 males with an average follow-up of 7.3 years (range 2.3-12.4
      years). A survivorship analysis was performed to determine the degeneration at
      the adjacent L5-S1 segment. Radiographs were analyzed for arthritic degeneration
      at that level. At the time of the L4-L5 index procedure, the L5-S1 disc spaces
      were graded on a 4-point scale for degeneration. Questionnaires were submitted by
      mail, and telephone interviews were conducted by one of the authors to determine
      the current level of patient function. RESULTS: Of the total 32 patients
      assessed, 31 (97%) had no evidence of symptomatic degeneration at L5-S1 requiring
      additional decompression or fusion. One patient had clinical symptoms that
      required a foraminotomy and laminotomy at L5-S1, but none of the patients
      required any further fusion. Although there was a trend of progression of the
      arthritic grade at L5-S1 from preoperative to postoperative examination, there
      was no correlation between preoperative arthritic grade versus further
      degeneration. The discs showed progression of degeneration from an average score
      of 2.28 before surgery to a score of 2.49 after surgery at the last follow-up.
      CONCLUSION: There appears to be no need to routinely include the L5-S1 segment
      when performing a posterior lumbar fusion for patients with instability or
      stenosis at L4-L5 if no symptoms are attributed to the lumbosacral level. At an
      average of 7.3 years, there was neither increased symptomatic disc degeneration
      nor symptoms necessitating the need for an L5-S1 fusion.

PMID- 12811274
TI  - Updated method guidelines for systematic reviews in the cochrane collaboration
      back review group.
AB  - STUDY DESIGN: Descriptive method guidelines. OBJECTIVES: To help reviewers
      design, conduct, and report reviews of trials in the field of back and neck pain.
      SUMMARY OF BACKGROUND DATA: In 1997, the Cochrane Collaboration Back Review Group
      published method guidelines for systematic reviews. Since its publication, new
      methodologic evidence emerged and more experience was acquired in conducting
      reviews. METHODS: All reviews and protocols of the Back Review Group were
      assessed for compliance with the 1997 method guidelines. Also, the most recent
      version of the Cochrane Handbook (4.1) was checked for new recommendations. In
      addition, some important topics that were not addressed in the 1997 method
      guidelines were included (e.g., methods for qualitative analysis, reporting of
      conclusions, and discussion of clinical relevance of the results). In May 2002,
      preliminary results were presented and discussed in a workshop. In two rounds, a
      list of all possible recommendations and the final draft were circulated for
      comments among the editors of the Back Review Group. RESULTS: The recommendations
      are divided in five categories: literature search, inclusion criteria,
      methodologic quality assessment, data extraction, and data analysis. Each
      recommendation is classified in minimum criteria and further guidance. Additional
      recommendations are included regarding assessment of clinical relevance, and
      reporting of results and conclusions. CONCLUSIONS: Systematic reviews need to be
      conducted as carefully as the trials they report and, to achieve full impact,
      systematic reviews need to meet high methodologic standards.

PMID- 12811273
TI  - Proximal neuromuscular impairment in lumbar disc herniation: a prospective
      controlled study.
AB  - STUDY DESIGN: A prospective and controlled study investigated the relation of
      muscle dysfunction to residual pain and disability in patients with lumbar disc
      herniation. OBJECTIVES: To determine the incidence of lower limb muscle
      dysfunction in lumbar disc herniation and its evolution over time after surgery,
      and to ascertain whether neuromuscular dysfunction has a prognostic value
      regarding pain and disability. SUMMARY OF BACKGROUND DATA: Residual sciatica, low
      back pain, and disability are common after lumbar discectomy. Preoperative motor
      dysfunction corresponding to the afflicted nerve root is often seen. METHODS: The
      participants in this study were 71 patients, ages 15 to 50 years, with disc
      prolapse at L4-L5 or L5-S1. Before surgery, then 6 weeks, 4 months, and 12 months
      after surgery, low back pain and leg pain were estimated on a visual analog
      scale, and disability was determined according to the Roland-Morris Questionnaire
      and a designed functional muscle test. RESULTS: Motor function of the sciatic leg
      frequently was impaired. Inferior outcome of proximal motor tests 6 weeks after
      surgery predicted pain and disability 1 year after surgery. The mean leg pain was
      59 mm before surgery and 15 mm at 6 weeks, remaining at that level during the
      follow-up period. The mean disability score was 14.4 before surgery, 8.8 at 6
      weeks, and 4.7 at 4 and 12 months, whereas muscle function improved gradually
      through 1 year of follow-up evaluation. CONCLUSIONS: Neuromuscular dysfunction
      frequently is present in patients with lumbar disc herniation. Sciatica resolves
      quickly after surgery, whereas disability improves gradually up to 4 months and
      muscular performance improves throughout the first year. Proximal muscular
      dysfunction in lumbar disc herniation has a prognostic value concerning residual
      pain and disability.

PMID- 12811275
TI  - Comparison of one-stage versus two-stage anteroposterior spinal fusion in
      pediatric patients with cerebral palsy and neuromuscular scoliosis.
AB  - STUDY DESIGN: A retrospective study was performed including 45 pediatric patients
      with spastic quadriplegic cerebral palsy and neuromuscular scoliosis who
      underwent anteroposterior spinal fusion. OBJECTIVES: To evaluate the outcomes and
      complications of one-stage and two-stage combined anteroposterior spine fusion
      and to document which procedure is more efficacious and provides better results.
      SUMMARY OF BACKGROUND DATA: Circumferential spinal arthrodesis has been proven to
      achieve better scoliotic curve correction, decreasing significantly the risk of
      pseudarthrosis and progression of the deformity. There have been a few studies
      comparing same-day versus staged anteroposterior spinal surgery in mixed
      populations with neuromuscular scoliosis, but not in an isolated group of
      pediatric patients with spastic cerebral palsy. METHODS: The medical records and
      radiographs of all patients were reviewed, and the results were statistically
      analyzed. The complications were divided into medical, subcategorized into major
      and minor, and technical. RESULTS: There was no statistically significant
      difference (P > 0.05) between one-stage (Group 1) and two-stage (Group 2)
      patients, considering age at surgery, preoperative scoliosis angle, pelvic
      obliquity, kyphosis angle, lordosis angle, levels of anterior release, percentage
      of scoliosis correction, radiographic follow-up, hospitalization time, and
      intensive care unit stay. Sequentially performed spinal procedures (Group 1) were
      associated with increased intraoperative blood loss, prolonged operative time,
      and a considerably higher incidence of medical and technical complications,
      including two perioperative deaths. CONCLUSION: Two-stage anteroposterior spinal
      fusion provides safer and more consistent results with several advantages over
      the single-stage procedure in the management of patients with cerebral palsy and
      neuromuscular scoliosis.

PMID- 12811276
TI  - Dual-rod correction and instrumentation of idiopathic scoliosis with the Halm
      Zielke instrumentation.
AB  - STUDY DESIGN: A prospective clinical and radiographic evaluation of 45
      consecutive patients with idiopathic adolescent and adult scoliosis treated with
      anterior dual-rod Halm-Zielke instrumentation. OBJECTIVES: Clinical and
      radiographic evaluation with a minimum follow-up of 2 years. SUMMARY OF
      BACKGROUND DATA: Halm-Zielke instrumentation was developed to eliminate the
      disadvantages of Zielke instrumentation in terms of lack of primary stability and
      a kyphogenic effect. METHODS: All patients underwent an identical anterior
      surgical technique with the Halm-Zielke instrumentation of the primary curve. The
      system is composed of a lid-plate, which is fixed to the lateral aspect of the
      vertebral body with two screws: a sunk screw anteriorly and a ventral derotation
      spondylodesis (VDS) screw posteriorly. The lid-plate design provides the lowest
      possible implant profile. The longitudinal components consist of a threaded rod
      and a solid, fluted rod. Correction is performed with both the threaded and the
      solid rod. The solid rod allows derotation and correction of the sagittal plane
      and provides primary stability. RESULTS: Preoperative curves ranged from 35
      degrees to 92 degrees Cobb angle. Final correction of the frontal plane averaged
      67% within the instrumented levels and 59% for the total primary curve. The
      apical vertebral rotation of the primary curve was corrected by 52% on average
      without loss of correction during follow-up. Thoracolumbar kyphosis was present
      in 11 patients and corrected in all cases from an average of 20 degrees to 2
      degrees after surgery and to 8 degrees at follow-up. We observed two cases of
      implant failure with one resulting in a pseudarthrosis. CONCLUSION: Halm-Zielke
      instrumentation proved to be a major improvement of the original VDS-Zielke. It
      eliminates the kyphogenic effect and provides primary stability.

PMID- 12811277
TI  - 18-Fluorine fluorodeoxyglucose positron emission tomography for the diagnosis of
      infection in the postoperative spine.
AB  - BACKGROUND: Using conventional imaging methods, including magnetic resonance
      imaging and labeled leukocyte scanning, the diagnosis of infection in the
      postoperative spine remains a diagnostic challenge. Recently, promising results
      have been reported using 18F-fluorodeoxyglucose positron emission tomography for
      various infectious problems. This study aimed to investigate the value of 18F
      fluorodeoxyglucose positron emission tomography in patients suspected of having
      spinal infection after previous surgery of the spine. METHODS: Fifty-seven
      consecutive patients with a history of previous spinal surgery were prospectively
      included between February 1999 and June 2001. 18F-fluorodeoxyglucose positron
      emission tomography was performed 60 to 90 minutes after injection of 370 MBq 18F
      fluorodeoxyglucose. Images were scored visually and semiquantitatively by two
      blinded, independent, certified nuclear medicine physicians, experienced with
      positron emission tomography. Differences were assessed by consensus. Results
      were correlated with final diagnosis allowing calculation of sensitivity,
      specificity and accuracy. Receiver operating characteristic analysis was
      performed to find optimal cut-off values. RESULTS: Fifteen patients had spinal
      infection. Using the most sensitive cut-off values sensitivity, specificity and
      accuracy were 100%, 81%, and 86%, respectively, for both visual and
      semiquantitative scoring. In the group without metallic implants (n = 27), false
      positives (n = 2) only occurred in the first 6 months after surgery. In the group
      with metallic implants (n = 30), false positives (n = 6) were not confined to
      recently operated patients. CONCLUSIONS: Overall accuracy was excellent (86%)
      with a negative predictive value of 100%. 18F-fluorodeoxyglucose positron
      emission tomography holds promise to become the standard imaging technique in
      this difficult patient population, as it is straightforward, provides a rapid
      result (2 hours) and because accurate alternatives are lacking.

PMID- 12811278
TI  - Metal concentrations in the serum and hair of patients with titanium alloy spinal
      implants.
AB  - STUDY DESIGN: A retrospective study of serum and hair metal concentrations in
      patients with titanium alloy spinal implants was performed. OBJECTIVE: To
      determine the incidence and possible causes of abnormal metal concentrations.
      SUMMARY OF BACKGROUND DATA: Several studies have demonstrated that metal debris
      are present in the tissues surrounding titanium alloy spinal implants. However,
      few studies suggest that metals dissolve, circulate in the body fluid, and
      accumulate in remote organs. METHODS: Titanium, aluminum, and vanadium
      concentrations in serum and hair were measured after surgery in 46 patients with
      titanium alloy spinal implants (12 patients in the implant failure group and 34
      patients in the no implant failure group) and 20 patients without spinal implants
      (control group). All the subjects were examined again 1 year after the first
      examination or implant removal. RESULTS: Of the 46 patients with titanium alloy
      spinal implants, 16 patients (34.8%) exhibited abnormal serum metal
      concentrations and 11 patients (23.9%) exhibited abnormal hair metal
      concentrations. In the control group, three patients (15%) exhibited only
      abnormal serum and metal aluminum concentrations at the first examination. In
      both of the two patients who exhibited abnormal serum titanium concentrations and
      then had their spinal implants removed, the serum and hair titanium levels
      decreased to beneath the reference value limit in 1 year after the removal.
      Comparison of the implant failure and no implant failure groups showed no
      significant differences in the incidence of abnormal serum concentrations of
      titanium, aluminum, or both metals. Therefore, serum metal concentrations did not
      seem to be a useful indicator of hardware loosening or implant failure.
      CONCLUSIONS: Approximately one third of patients with titanium alloy spinal
      implants exhibited abnormal serum or hair metal concentrations at a mean time of
      mean 5.1 years after surgery. Titanium or aluminum may travel to distant organs
      after dissolution of metals from the spinal implants.

PMID- 12811279
TI  - Pain immediately upon sitting down and relieved by standing up is often
      associated with radiologic lumbar instability or marked anterior loss of disc
      space.
AB  - STUDY DESIGN: Comparison of functional radiographs in consecutive patients with
      low back pain with or without pain on sitting down and relieved by standing up.
      OBJECTIVES: To detect radiologic signs possibly associated with a clinical
      symptom. SUMMARY OF BACKGROUND DATA: No link has been established between
      increased vertebral mobility and a specific pain pattern or a clinical symptom.
      METHODS: Forty-two patients seen consecutively with low back pain occurring
      immediately on sitting down and relieved on standing up were compared with 32
      controls whose low back pain did not show this pattern. Dynamic radiographs were
      taken in extension, erect, flexion, and sitting in the painful position. The
      segments thought to be responsible for the pain were identified by comparing
      clinical, radiographic, and magnetic resonance data. Endplate angles, rotation,
      and translation were measured. The radiographs were read twice each by two
      independent observers. RESULTS: Eighty-six percent (95% confidence interval, 72
      99%) of the patients with the symptom were female. The segments identified as the
      source of pain were as follows: L4-L5 in 20 cases and L1-L2 to L3-L4 in 22 cases.
      Mean rotation of these segments was 13.9 +/- 4.5 degrees in the patient group
      versus 7.5 +/- 4.3 degrees in the control group (P < 0.001). In 14% of the
      patients (vs. 3% of controls), it exceeded 20 degrees (P = 0.13). Anterior or
      posterior translation >10% was seen in 31% of the patients (vs. 0% of controls; P
      < 0.001). In flexion, the endplate angle was -5.2 +/- 3.6 degrees (patients)
      versus 1.2 +/- 5.7 degrees (controls) (P < 0.01) and <-5 degrees in 55% of
      patients versus 12.5% of controls (P < 0.001). This value of <-5 degrees was
      associated with marked anterior loss of disc space. CONCLUSION: Low back pain
      occurring immediately on sitting down and relieved on standing up was
      statistically associated with instability (specificity 100%, sensitivity 31%) or
      marked anterior loss of disc space in flexion (specificity 87%, sensitivity 55%).

PMID- 12811281
TI  - Risk factors for sickness absence because of low back pain among scaffolders: a 3
      year follow-up study.
AB  - STUDY DESIGN: A prospective cohort study was conducted. OBJECTIVE: To find risk
      factors for short-term (<or=14 days) and long-term (>14 days) sickness absence
      because of low back pain among scaffolders. SUMMARY OF BACKGROUND DATA: Although
      some studies have described the relation between work-related risk factors for
      musculoskeletal disease and sickness absence, little is known about the role of
      individual, physical, and psychosocial factors and different end points of low
      back pain as risk factors for sickness absence among scaffolders. METHODS:
      Between 1998 and 2001, 222 scaffolders and 66 supervisors (response rate, 86%)
      completed a questionnaire at baseline. In addition, data on sickness absence were
      collected from absence records. RESULTS: At baseline, 60% of the study population
      had experienced an episode of low back pain in the 12 months preceding the
      investigation, 37% of which were of chronic nature. During the follow-up period,
      34% of the population had been on sick leave for at least one episode of low back
      pain. The risk factors for sickness absence less than 2 weeks were a high
      physical load from strenuous arm movements and severe low back pain. Workers with
      severe low back pain were at higher risk for sickness absence longer than 2
      weeks. Psychosocial workload and individual characteristics did not predict the
      occurrence of sickness absence because of low back pain. CONCLUSIONS: Because
      work-related physical load was a risk factor for sickness absence less than 2
      weeks and severe low back pain was a risk factor for sickness absence both
      shorter than and longer than 2 weeks, a focus on secondary prevention for
      scaffolders with severe low back pain is advised.

PMID- 12811280
TI  - Pelvic bone asymmetry in 323 study participants receiving abdominal CT scans.
AB  - STUDY DESIGN: Retrospective review of all CT scans of pelvis and abdomen
      performed at our institution in October and November 2000. OBJECTIVE: To
      determine the prevalence and extent of radiographic pelvic asymmetry in a
      population of patients not preselected for having low back pain. SUMMARY OF
      BACKGROUND DATA: Pelvic asymmetry refers to asymmetric positioning of landmarks
      on the two sides of the pelvis and may have a structural or functional etiology.
      Pelvic asymmetry can be associated with the presence of true leg length
      discrepancy, lead to false diagnosis or inaccurate measurement of leg length
      discrepancy, or itself be independently associated with back pain. Although the
      prevalence of pelvic asymmetry has been reported in patients with back pain to be
      24-91%, its prevalence in the general population is not known. METHODS: A total
      of 323 consecutive CT scans of the pelvis/abdomen were assessed for pelvic
      asymmetry by one of three examiners. Pelvic asymmetry was defined as an unequal
      distance from the iliac crests to the acetabuli bilaterally, measured on the
      anteroposterior scout view of the CT scan. Measurements made on 30 randomly
      selected scans by the three examiners were used to assess interrater reliability
      of the measurement method. RESULTS: Pelvic asymmetry ranged in magnitude from -11
      mm to 7 mm [right pelvis (mm) - left pelvis (mm)]. Pelvic asymmetry was >5 mm in
      17 of 323 (5.3%) and >10 mm in 2 of 323 (0.6%) of the subjects; 172 of 323
      (53.3%) had a smaller right hemipelvis (mean asymmetry = -3.0 mm). A total of 95
      of 323 (29.4%) had a smaller left hemipelvis (mean asymmetry = 2.1 mm). The
      intraclass correlation coefficient [ICC(2,1)] between the three observers was
      high (0.91). CONCLUSION: Pelvic asymmetry of >5 mm was uncommon, with a
      prevalence of approximately 5% in the population studied. CT scanography was
      found to be a practical and reliable method for the assessment of suspected
      pelvic asymmetry.

PMID- 12811282
TI  - Side of symptomatic annular tear and site of low back pain: is there a
      correlation?

PMID- 12811283
TI  - Chronic pain of spinal origin.

PMID- 12811284
TI  - Bovine thrombin induces an acquired coagulopathy in sensitized patients
      undergoing revision spinal surgery: a report of two cases.
AB  - STUDY DESIGN: A report of two cases is presented. OBJECTIVE: To raise awareness
      of bovine thrombin-induced factor V deficiency. SUMMARY OF BACKGROUND DATA:
      Bovine thrombin is a frequently used hemostatic agent in spinal surgery. Current
      preparations contain clotting factors in addition to thrombin, particularly
      factor V, which are immunogenic. Re-exposure of sensitized patients to bovine
      thrombin products during subsequent surgery may lead to the formation of
      antibodies that cross-react with human clotting factors, most commonly against
      factor V. Hemorrhagic complications have been reported in nonspinal patients due
      to a bovine thrombin-induced factor V deficiency. METHODS: Two spinal cases are
      reported, and the literature is reviewed. RESULTS: In the cases outlined, both
      patients underwent revision spinal surgery, with re-exposure to bovine thrombin.
      Both patients developed abnormal coagulation profiles, with an acquired factor V
      deficiency. No hemorrhagic complications occurred; however, second-stage surgery
      was delayed in one patient and not undertaken in the other. In both patients, the
      coagulopathy resolved spontaneously. CONCLUSIONS: Bovine thrombin-induced
      coagulopathy is well recognized in cardiac surgery but has not been reported in
      spinal surgical patients. Data available from cardiac surgical patients suggests
      that those who are sensitized to two or more bovine clotting factors are at
      greatest risk of hemorrhagic complications. The cases we present demonstrate that
      this phenomenon occurs in spinal surgical patients and serve to raise awareness
      of the potential danger of bovine thrombin in sensitized patients.

PMID- 12811285
TI  - Congenital partial aplasia of the posterior arch of the atlas causing myelopathy:
      case report and review of the literature.
AB  - STUDY DESIGN: A case report of a patient with a congenital anomaly of the
      posterior arch of the atlas and review of the literature are reported. OBJECTIVE:
      To describe a unique presentation of cervical myelopathy caused by a mobile
      isolated bone fragment in an otherwise healthy young male. The description is
      supplemented by a video showing the repeated trauma the bone fragment caused to
      the dorsal spinal cord with neck extension. SUMMARY OF BACKGROUND DATA:
      Congenital anomalies of the posterior arch of C1 are well described and are
      almost always asymptomatic and found incidentally. Neurologic symptoms, either of
      a chronic nature or developing acutely following head or neck trauma, have been
      described in patients with isolated posterior arch tubercles (Types C or D).
      METHODS: A 17-year-old male developed sensory deficit in his distal lower
      extremities acutely that progressed over several weeks proximally and into his
      left upper extremity. He also described a Lhermitte sign, only with extension of
      his neck and an episode of temporary quadriparesis with a minor fall. Plain
      radiographs and a computed tomography scan of his neck revealed a congenital
      deformity of the posterior arch of the atlas. Magnetic resonance imaging showed
      T1 and T2 signal abnormality within the posterior spinal cord at the level of C1
      to C2. RESULTS: The patient underwent flexion and extension movements under
      fluoroscopy, which showed the posterior tubercle moving anteriorly and
      compressing the spinal cord every time he extended his neck. The fragment was
      resected, and, intraoperatively, dense fibrous tissue was found to be bridging
      the bony defect. After surgery, his sensory deficits almost completely resolved,
      and he no longer had a Lhermitte phenomenon. CONCLUSION: This case illustrates a
      symptomatic congenital deformity of the posterior arch of the atlas due to a
      mobile, isolated fragment. These anomalies are exceedingly rare. To date, only 17
      patients, including ours, have been described in the literature as having
      myelopathy related to an isolated posterior tubercle. Of these, only two patients
      had documented movement of this tubercle before our report. Recognizing the
      anomaly is crucial because treatment is relatively simple, produces resolution of
      symptoms, and prevents major neurologic deficits from occurring after trauma.

PMID- 12811286
TI  - Kinematic magnetic resonance imaging of a thoracic spinal extradural arachnoid
      cyst: an alternative suggestion for exacerbation of symptoms during straining.
AB  - STUDY DESIGN: A case study of an extradural arachnoid cyst using kinematic
      magnetic resonance imaging. OBJECTIVES: To access the dynamic and pathologic
      changes of an extradural subarachnoid cyst during straining by kinematic magnetic
      resonance imaging and to clarify the pathomechanism of a fluctuation in symptoms.
      SUMMARY OF BACKGROUND DATA: Extradural arachnoid cysts of the spine are an
      uncommon cause of myelopathy secondary to spinal cord compression; however, the
      precise mechanism of cord compression and subsequent symptoms remain unclear.
      METHODS: A 31-year-old female presented with severe left lower thoracic back pain
      and leg stiffness, which were exacerbated by coughing and straining. She was
      diagnosed with an extradural subarachnoid cyst by magnetic resonance imaging.
      Kinematic magnetic resonance imaging was carried out to assess the dynamic change
      of the extradural cyst and to demonstrate the mechanism causing her chest pain
      and leg stiffness during straining. RESULTS: Kinematic magnetic resonance imaging
      demonstrated that the cyst wall was compressed, and the size of extradural cyst
      was decreased for several seconds during straining. Furthermore, the ring of
      cerebrospinal fluid was gradually compressed circumferentially. After surgery,
      the patient experienced complete relief of symptoms. Postoperative kinematic
      magnetic resonance imaging revealed good decompressive results had been obtained,
      and the ring of cerebrospinal fluid was preserved even when the patient strained
      for a few minutes. CONCLUSIONS: Kinematic magnetic resonance imaging study
      demonstrated that pressure changes which occur in the extradural space as well as
      in the arachnoid cyst might cause spinal cord compression and result in
      intermittent exacerbation of symptoms.

PMID- 12811287
TI  - Painful lumbosacral melorheostosis treated by fusion.
AB  - STUDY DESIGN: A case report of low back pain associated with a diagnosis of
      melorheostosis of the lumbosacral spine. OBJECTIVE: To describe a rare
      presentation of melorheostosis and subsequent successful surgical treatment.
      SUMMARY OF BACKGROUND DATA: Melorheostosis is a rare condition and spinal pain
      has not been described in association with the condition. METHODS: A patient with
      disabling low back pain and suspected melorheostosis of the lumbosacral spine
      responded favorably to diagnostic facet joint blocks. Treatment was lumbosacral
      fusion and biopsy of the abnormal bone. The densely sclerotic bone presented
      technical difficulties requiring modification of surgical technique. RESULTS:
      Dramatic pain and disability reduction occurred following lumbosacral fusion.
      Histologic examination was consistent with melorheostosis. CONCLUSION:
      Melorheostosis rarely causes severe low back pain that can respond favorably to
      fusion surgery.

PMID- 12811288
TI  - Pyogenic osteomyelitis of the odontoid process: single stage decompression and
      fusion.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To document our experience with single
      stage decompression and fixation in the treatment of pyogenic osteomyelitis of
      the odontoid process. SUMMARY OF BACKGROUND DATA: Although several investigators
      have reported a handful of these unusual cases, up until now, there have been no
      studies concerning a single stage solution in the surgical treatment of this
      pathology. METHODS: Three patients with osteomyelitis of the odontoid process
      caused by Staphylococcus aureus underwent surgical treatment in single sessions
      (transoral decompression combined with posterior fusion as the second step of the
      operation). Following surgery, the patients underwent a 6-week antibiotic course
      administered both intravenously and orally. Furthermore, we recommended the use
      of a hard cervical collar for 8 weeks together with isometric rehabilitation of
      the cervical muscles. Currently, follow-up results are available for two
      patients. RESULTS: On examination at 3 months, 6 months, and 1 year after the
      surgery, both patients had completely recovered with no neurologic deficit. Plain
      radiographs showed complete posterior fusion after 6 and 12 months, respectively.
      CONCLUSIONS: We emphasize the advantages of our method in comparison with
      nonoperative treatment or multisession surgery. The single stage surgical
      solution led to a shortening of hospitalization time with no need for halo
      bracing, to excellent results with respect to C-spine stability and to better
      compliance from the patients.

PMID- 12811290
TI  - Evaluation of lower urinary tract symptoms in females.
AB  - PURPOSE OF REVIEW: Ongoing controversy exists as to the extent of the necessary
      evaluation of the female presenting with lower urinary tract symptoms. Most would
      agree that a detailed history, a physical examination and a urine analysis are
      essential components of the initial evaluation of lower urinary tract symptoms in
      the female. Beyond these assessments, however, there are no universally accepted
      guidelines or recommendations. In selected patients, a urodynamic, endoscopic
      and/or radiographic evaluation may be indicated. When further investigation of
      lower urinary tract symptoms is being considered, individual test
      characteristics, including sensitivity, specificity, reproducibility and
      accuracy, must be balanced against such factors as cost, morbidity, discomfort,
      availability and invasiveness. This review discusses some of the recent reports,
      controversies and developments in the evaluation of lower urinary tract symptoms
      in the female, and briefly reviews the most recent relevant International
      Continence Society subcommittee publications. RECENT FINDINGS: The proceedings of
      the International Consultation on Incontinence, as well as recent publications by
      a number of its subcommittees, have provided some guidance for the structured
      evaluation of lower urinary tract symptoms in the female, especially with regard
      to the investigation of urinary incontinence. The role of urodynamics and
      radiographic imaging continues to be refined. Magnetic resonance imaging is, at
      present, still primarily a research tool in the evaluation of lower urinary tract
      disorders in the female; however, a clinical role for this technology is
      evolving. SUMMARY: The goal of a diagnostic evaluation is the accurate
      characterization of lower urinary tract symptoms for the purposes of treatment.
      Ideally, a brief, low-cost, non-invasive evaluation would provide a high degree
      of diagnostic accuracy. However, existing technology is limited in this regard.
      Until future refinements permit a completely non-invasive, cost-effective and
      accurate analysis of female lower urinary tract symptoms, existing technology
      must be appropriately utilized. Well-conducted, evidence-based, prospective
      studies are needed.

PMID- 12811291
TI  - Recent advances in management of female lower urinary tract trauma.
AB  - PURPOSE OF REVIEW: Abdominal and pelvic injuries are often associated with
      devastating lower urinary tract injuries. The literature is replete with studies
      involving male lower urinary tract trauma, however the diagnosis and management
      of similar injuries in women is not as well covered. In this article we will
      review recent advances in the diagnosis and management of female lower urinary
      tract trauma. RECENT FINDINGS: The recent literature emphasizes the importance of
      diagnosing and managing female lower urinary tract injuries, both of the bladder
      and the urethra, caused by blunt or penetrating trauma to the lower abdomen,
      pelvis and perineum. Successful management of these injuries is based upon
      accurate diagnosis, recognition of associated injuries, and prompt treatment.
      Diagnosis and treatment of female bladder perforation have been well established.
      Reports of female urethral injuries are scarce, however, and subsequently the
      management is not standardized. SUMMARY: High suspicion, accurate diagnosis and
      prompt treatment are key for the successful management of female lower urinary
      tract injuries associated with lower abdominal, pelvic and perineal trauma. A
      standardized algorithm for management of female urethral injuries would be
      helpful.

PMID- 12811292
TI  - Recent developments in the management of detrusor overactivity.
AB  - PURPOSE OF REVIEW: Detrusor overactivity is a relatively common yet embarrassing
      symptom complex with significant impact on quality of life. The mainstay of
      current pharmacological treatment involves use of muscarinic receptor
      antagonists, but their therapeutic efficacy is limited by their troublesome side
      effects resulting in the non-continuance of treatment in a significant number of
      patients. Therefore, the development of new drugs can proceed by targeting
      alternative pathways affecting detrusor overactivity. In this article, the
      pharmacological basis for the current therapeutic alternatives for managing
      detrusor overactivity and possible future developments are discussed. RECENT
      FINDINGS: It is clear that far from being a passive container for urine, the
      urothelium is a crucial part of the bladder. Its functions are complex, dynamic
      and important, and only now becoming understood. The release of ATP from
      urothelium in response to distension and its action on P2X receptors resulting in
      activating both motor and sensory neurons is being increasingly recognised. In
      the normal bladder, muscarinic receptor stimulation produces the main part of
      detrusor contraction. However, in functionally abnormal bladders, a non
      cholinergic activation via the purinergic receptors may occur. The central
      nervous mechanisms controlling the micturition reflex have also recently
      attracted attention. SUMMARY: Recent research has suggested that several
      transmitters may modulate voiding. However, few drugs with clinical benefits have
      been developed so far. Present treatments for overactive bladders have
      significant non-compliance rates. Hopefully, future research will lead to drugs
      with greater therapeutic benefits and better tolerance.

PMID- 12811293
TI  - The management of female voiding dysfunction: Fowler's syndrome -- a contemporary
      update.
AB  - PURPOSE OF REVIEW: Several aspects of voiding dysfunction in women remain under
      investigation, including standardization of the diagnosis and management of
      bladder outflow obstruction. This article describes a specific cause of urinary
      retention in young women, associated with a failure of urethral sphincter
      relaxation, and a treatment option that can restore voiding in this group of
      patients - sacral nerve electrical stimulation therapy. Recently there have been
      advances in the stimulator implantation technique, as well as in our appreciation
      of its mechanism of action. RECENT FINDINGS: Advances include the use of
      ancillary investigations such as urethral function tests as well as better
      understanding of the clinical profile of these patients. Improvements in the
      surgical technique include better methods of lead fixation and a less invasive
      surgical approach. Research suggests the action of neuromodulation is on the
      afferent pathway, though it remains to be shown whether this is at a spinal or
      supraspinal level. It is likely that sacral nerve stimulation has an indirect
      modulatory effect on detrusor contractility rather than a direct effect on the
      sphincter. SUMMARY: Experience of sacral nerve stimulation has increased over the
      past few years, and its application is expanding to other clinical domains. This
      knowledge has helped improve the therapy, which is particularly effective in the
      treatment of women with urinary retention. Although how it works is still not
      fully understood, this is something that is being addressed by ongoing research.

PMID- 12811294
TI  - Are slings now the gold standard treatment for the management of female urinary
      stress incontinence and if so which technique?
AB  - PURPOSE OF REVIEW: Sling surgery for the treatment of female stress urinary
      incontinence has become so popular as a consequence of excellent results that
      possibly the time has come to consider this type of surgery as the new gold
      standard. Prior to reaching this conclusion careful consideration of the
      developments that have led to this perception are necessary. These reflections
      should include (patho)physiology, historical background, and alternative
      techniques and materials. RECENT FINDINGS: Pathophysiological concepts and
      theories on clinical staging have changed in recent years. The importance of
      pressure transmission and hammock-like support has been complemented by the so
      called 'integral' theory. Analysis of the available literature shows that the new
      sling procedures provide a new reference point in time because they not only show
      good medium-term results, but they are also minimally invasive with quick post
      operative recovery. SUMMARY: Loosely applied mid-urethral slings are the new gold
      standard therapy for female stress urinary incontinence. Whether these slings
      should be made of synthetic material (polypropylene) or bio-material (allografts
      or xenografts) can only be determined after comparative randomized controlled
      trials. Bio-materials have the advantage of versatility that makes them useful as
      a loose sling in patients with a 'good' urethra or as a tight sling in patients
      with a 'bad' urethra. Furthermore, synthetic materials carry with them the risk
      of complications associated with any nonabsorbable material such as erosion. The
      field of stress incontinence treatment is evolving continuously and no doubt
      current techniques will be surpassed by newer, better concepts in the future.

PMID- 12811295
TI  - Recent developments in the management of interstitial cystitis.
AB  - PURPOSE OF REVIEW: Interstitial cystitis, a great enigma of urology today, is a
      chronic sterile inflammatory disease of the bladder of unknown etiology
      characterized by urinary frequency, urgency, nocturia and suprapubic pain.
      Although there are plenty of theories, the etiology of the condition remains
      obscure. This review focuses on recently published literature on interstitial
      cystitis. RECENT FINDINGS: Several pathophysiological mechanisms have been
      proposed in the past few years including epithelial dysfunction, activation of
      mast cells, neurogenic inflammation, autoimmunity and occult infection. Evidence
      indicates that it is a heterogeneous syndrome and that the two subtypes, classic
      and nonulcer disease, represent different entities. The diagnosis is made by
      clinical and cystoscopic evaluation with hydrodistension and often with biopsy
      when other disorders are excluded. The National Institute of Arthritis, Diabetes,
      Digestive and Kidney Diseases has developed criteria for clinical studies. There
      is a need for a noninvasive marker of interstitial cystitis. Antiproliferative
      factor as a urinary marker has shown promising results. The value of the bladder
      permeability test in interstitial cystitis needs further investigation. Many
      gynecologic conditions mimic the symptoms of interstitial cystitis. Multiple
      forms of therapy are available including self-care and dietary changes, medical
      and intravesical treatments, neuromodulation, multimodality treatment and
      surgical intervention. It is recommended that the most conservative treatments
      are used first and surgery should be regarded as the last resort. SUMMARY:
      Interstitial cystitis is a challenging disease of urology today. While causative
      factors remain unknown, treatment is based on empiricism. Intensive research may
      result in new and hopefully more effective treatments in the future.

PMID- 12811296
TI  - What's new in prolapse surgery?
AB  - PURPOSE OF REVIEW: There are very many types of operation for the correction of
      symptomatic pelvic floor relaxation, and the pelvic surgeon is faced with a
      difficult task when selecting the most appropriate procedure(s) for an individual
      patient. Currently, the lifetime risk of undergoing prolapse or continence
      surgery in France is one in 11; up to 30% of patients will require repeat
      prolapse surgery, and 10% will require repeat continence surgery. Reconstructive
      pelvic surgery for the treatment of vaginal prolapse continues to evolve as
      surgeons continue their quest for a definitive surgical cure. This review looks
      at the etiology, presentation and current surgical management of genital prolapse
      in females. RECENT FINDINGS: There are three primary routes of access in
      reconstructive pelvic surgery (abdominal, vaginal and laparoscopic) for the
      repair of anterior, superior and posterior defects; the choice often depends on
      the surgeon's experience. Of the abdominal repairs, abdominal sacrocolpopexy with
      mesh remains the 'gold standard'; the retropubic paravaginal repair and
      laparoscopic techniques have not gained widespread acceptance. The laparoscopic
      approach appears to be the least utilized, because of the great degree of
      technical difficulty associated with laparoscopic suturing. Of the vaginal
      restorative procedures, uterosacral ligament vault suspension and iliococcygeous
      and sacrospinous fixation have their proponents. However, there is increasing
      interest in the use of biological prostheses (allografts/xenografts) and
      synthetic absorbable meshes. SUMMARY: Randomized controlled trials are required
      to evaluate the role of surgical procedures in reconstructive surgery, to
      determine which type of prosthesis is most suitable.

PMID- 12811297
TI  - Posterior urethral valves: lessons learned over time.

PMID- 12811298
TI  - Paediatric laparoscopic surgery.
AB  - PURPOSE OF REVIEW: Laparoscopic procedures in paediatric urology are gaining
      popularity, with an increasing number of centres performing advanced surgery.
      Indications have expanded from diagnostic to ablative surgery and more recently
      to reconstructive procedures. The current status of the indications and results
      of different laparoscopic procedures dealing with paediatric urology are
      reviewed. RECENT FINDINGS: Laparoscopic orchiopexy for intra-abdominal testis
      gives better results than classic open surgery procedures. Palomo modified
      varicocelectomy with lymphatic preservation is the optimal surgical procedure to
      treat varicocele in adolescents. The retroperitoneal approach to renal surgery is
      gaining popularity. Total and partial nephrectomies are feasible in comparable
      operative times with open surgery and shortened hospital stays. Dismembered
      pyeloplasty remains a challenging procedure limited to few centres, with
      excellent midterm results. Laparoscopic adrenal surgery has been extended to
      neuroblastoma in selected cases. Laparoscopic transvesical ureteric re-implant is
      now feasible, and opens a new era in bladder surgery. Finally, results of the
      initial experience with robot-assisted pyeloplasty are now available in children,
      and showed similar results with regard to the postoperative course, but shorter
      operative times with experience. SUMMARY: The value of laparoscopic orchiopexy
      for intra-abdominal testis and ablative surgery such as total and partial
      nephrectomy and adrenalectomy has been confirmed. Robot-assisted laparoscopic
      surgery will probably popularize challenging procedures such as pyeloplasty and
      ureterovesical re-implant, which are still limited to a few centres. Despite an
      increase in the number of publications dealing with the results of laparoscopic
      procedures, efforts are still needed to validate the benefits of such procedures
      over open surgery.

PMID- 12811299
TI  - Nocturnal enuresis (bedwetting).
AB  - PURPOSE OF REVIEW: Nocturnal enuresis, or bedwetting, is an old but still
      prevalent clinical problem in childhood and adolescence. Recent research has
      helped to correct some traditional misconceptions and unveil the underlying
      pathophysiological mechanisms. This article reviews recent advances in our
      understanding of the pathophysiology and current management strategy for
      enuresis. RECENT FINDINGS: Nocturnal enuresis is a heterogeneous disorder with
      various underlying pathophysiological mechanisms, causing a mismatch between the
      nocturnal bladder capacity and the amount of urine produced during sleep at
      night, in association with a simultaneous failure of conscious arousal in
      response to the sensation of bladder fullness. Children with increased nocturnal
      urine production usually have a good response to desmopressin therapy. Patients
      with a small bladder almost invariably have various types of occult bladder
      dysfunction, but otherwise have a completely normal circadian rhythm of urine
      production. These patients generally have a poor response to desmopressin
      treatment, but would benefit more from combination therapy with enuretic alarm,
      urotherapy and antimuscarinic agents in addition to desmopressin. SUMMARY:
      Various factors can potentially influence the balance between nocturnal urine
      production and functional bladder capacity. Different types of bladder
      dysfunction, resulting in a small nocturnal bladder capacity, probably contribute
      significantly to the pathogenesis, particularly in those with treatment failure
      and refractory symptoms. As different clinical subgroups may have different
      responses to treatment, it is necessary to distinguish these subgroups before a
      decision on the specific treatment protocol can be made. These new insights have
      an important bearing in our future management strategy for bedwetting.

PMID- 12811300
TI  - Anticardiolipin antibodies in chronic viral hepatitis. Do they have clinical
      consequences?
AB  - Antiphospholipid antibodies are a heterogeneous group of acquired autoantibodies
      that react with anionic phospholipids, such as cardiolipin. Anticardiolipin
      antibodies (ACAs) are frequently found in patients with systemic lupus
      erythematosus and other autoimmune disorders and can react with the phospholipid
      alone or bound to the cofactor beta2-glycoprotein-I. This latter form of cofactor
      dependent ACAs is strongly associated with the occurrence of thrombotic events.
      ACAs have been observed to occur in both chronic hepatitis B and chronic
      hepatitis C as well as in other viral infections and in neoplastic diseases. In
      viral infection, ACAs are generally cofactor independent and may represent an
      epiphenomenon of the infection. Some studies, however, have found an increased
      incidence of thrombotic disorders in patients with chronic hepatitis C virus
      (HCV) who manifest ACA positivity suggesting that the presence of these
      autoantibodies may predispose to thrombosis in specific HCV-infected patients. In
      conclusion, ACAs are commonly found in patients with chronic viral infection but
      their pathogenetic role and the mechanisms that stimulate their production have
      not yet been clarified.

PMID- 12811301
TI  - Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D
      infection, and hepatitis B-related hepatocellular carcinoma. Relationship with
      portal vein thrombosis.
AB  - OBJECTIVE: To assess the presence of anticardiolipin antibodies (ACAs) in
      patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D
      virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to
      associate this with the incidence of portal vein thrombosis (PVT) in HCC
      patients. PATIENTS AND METHODS: Sixty-five cirrhotic patients with HBV-related
      HCC, 28 naive patients with chronic HBV infection and 14 naive patients with
      chronic HDV infection were enrolled prospectively in the study. Thirty-two
      healthy blood donors were used as controls. The ACAs (immunoglobulin G and
      immunoglobulin M) were measured using an enzyme-linked immunosorbent assay
      system. Statistical analysis used non-parametric methodology (chi-squared test,
      Student t-test and Fisher exact test, P value<0.05). RESULTS: Eleven of the 65
      patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients
      (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In
      contrast, from the 43 patients without PVT, only three (11%) showed a positive
      titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six
      out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six
      ACA positive HBV patients presented an extrahepatic manifestation of the disease.
      One out of 32 control patients (3%) had positive ACAs. CONCLUSION: Both chronic
      HBV and chronic HDV infections are potent stimulants for the production of ACAs.
      The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients
      with PVT suggests their possible participation in thrombotic mechanisms and in
      the hypercoagulable state that occurs in advanced liver disease and HCC.

PMID- 12811302
TI  - Quantitative evaluation of liver function by the methionine and aminopyrine
      breath tests in the early stages of liver transplantation.
AB  - OBJECTIVE: The early phase after liver transplant is considered the period of
      greatest risk for graft failure. In recent years breath tests have been proposed
      as a non-invasive method to assess liver function. In particular, the aminopyrine
      breath test is useful for evaluating the liver viable mass, and the methionine
      breath test could be used to evaluate oxidative capacity of liver mitochondria.
      We aimed to perform these tests in the early phase following liver transplant in
      order to correlate the time course of these tests to the outcome of
      transplantation. METHODS: Twenty-three patients undergoing liver transplant were
      enrolled. The methionine and aminopyrine breath tests were performed on the days
      1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were
      expressed as the percentage of administered 13C recovered per hour and as the
      cumulative percentage of the 13C dose recovered over the test period. RESULTS:
      All but two transplants were successful in the short term and the cumulative
      percentage of the dose of 13C progressively increased after transplantation,
      reaching values not significantly different from controls (methionine at day 5).
      In two patients, primary non-function occurred: in these patients the cumulative
      percentage of the 13C dose did not increase after orthotopic liver transplant and
      the results of both breath tests indicated that it always remained significantly
      lower compared to that of other patients. CONCLUSIONS: A combination of breath
      tests, exploring both mitochondrial and microsomal function, could be useful in
      the early phase after liver transplant in order to evaluate the graft outcome.

PMID- 12811303
TI  - Improvement of regional cerebral blood flow after treatment with branched-chain
      amino acid solutions in patients with cirrhosis.
AB  - OBJECTIVE: The administration of solutions rich in branched-chain amino acids
      leads to mental recovery from acute hepatic encephalopathy in patients with liver
      cirrhosis. However, the mechanism of action of branched-chain amino acids remains
      unclear. The purpose of this study was to evaluate the effect of intravenous
      infusion of branched-chain amino acids on brain perfusion in patients with liver
      cirrhosis. METHODS: Single photon emission computed tomography scans were
      performed in 14 patients with liver cirrhosis before and after the administration
      of branched-chain amino acids in a single-day split-dose protocol. The per cent
      change in regional brain perfusion was calculated in high frontal, parietal,
      temporal, occipital lobes and cerebellum. Thereafter, statistical parametric
      mapping was performed to identify brain regions with abnormal cerebral perfusion.
      RESULTS: Intravenous infusion of solutions enriched with branched-chain amino
      acids induced a 13-20% increase in regional cerebral blood flow. Cirrhotic
      patients had regions of significant hypoperfusion, as determined by statistical
      parametric mapping, in the left superior parietal and posterior cingulate as
      compared to the control group. This hypoperfusion of parietal and cingulate
      regions was not detected after treatment with solutions of branched-chain amino
      acids. CONCLUSIONS: The results of the present study suggest that administration
      of solutions enriched with branched-chain amino acids improves cerebral perfusion
      in patients with cirrhosis.

PMID- 12811304
TI  - Spontaneous bacterial peritonitis in the Czech Republic: prevalence and
      aetiology.
AB  - The aim of the study was to determine the prevalence and detailed data concerning
      the incidence of spontaneous bacterial peritonitis in the Czech Republic. Ninety
      nine patients with liver cirrhosis and ascites were examined. Spontaneous
      bacterial peritonitis was diagnosed in 35 patients (35.4%). It was revealed more
      often in patients with alcoholic aetiology of cirrhosis whose anamnesis involved
      sub-febrile or febrile states and the deterioration of ascites. Elevated serum
      leucocyte counts and increased levels of C-reactive protein can contribute to the
      diagnosis. A low level of total protein and albumin in ascites predisposes to the
      increase of this infection. The reduction of the platelet count in a set of
      patients with spontaneous bacterial peritonitis indicates the influence of portal
      hypertension in the aetiology of the disease.

PMID- 12811305
TI  - Functional and morphological aspects of Helicobacter pylori-induced gastric
      cancer in Mongolian gerbils.
AB  - BACKGROUND: Helicobacter pylori infection of Mongolian gerbils is an established
      model of gastric carcinogenesis, but gastric secretory aspects of this
      carcinogenesis have not been studied. METHODS: The effects of single intragastric
      inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) CFU/ml) or
      vehicle (saline) were examined at 1, 2, 4, 6, 9, 12 and 30 weeks from
      inoculation. Gastric morphology, the presence of H. pylori using the rapid urease
      test, the density of H. pylori and 16S rRNA and the plasma gastrin and
      somatostatin were determined. RESULTS: H. pylori was detected in gastric mucosa
      in all infected animals. Basal gastric acid in gerbils was reduced by about 50%
      after H. pylori inoculation. Early lesions seen at 4 weeks after H. pylori
      inoculation consisted of chronic gastritis with thickened mucosal folds, oedema,
      congestion and mucosal lymphocytic infiltration. Adenomatous hyperplasia with
      cellular atypia with increased mitotic activity and the formation of apoptotic
      bodies and visible erosions and ulcerations were observed at 12-30 weeks after
      inoculation. The atypical gastric glands were situated 'back-to-back', suggesting
      gastric pre-cancer. The gastric blood flow in H. pylori-infected gerbils was
      significantly lower than that in the controls. Six- to seven-fold increase in
      plasma gastrin levels combined with significant fall in gastric somatostatin
      contents and the intraepithelial neoplasia were noticed in gerbils at all tested
      periods. CONCLUSION: H. pylori-infection in gerbils resulted in gastric pre
      cancer associated with functional changes, such as suppression of gastric
      secretion and impairment of both gastric mucosal microcirculation and the gastrin
      somatostatin link.

PMID- 12811306
TI  - Somatostatin and D cells in patients with gastritis in the course of Helicobacter
      pylori eradication: a six-month, follow-up study.
AB  - BACKGROUND/AIMS: As well as causing chronic gastritis, Helicobacter pylori
      predisposes patients to peptic ulcer disease and gastric cancer, and induces
      gastric functional disorders. The aim of our study was to investigate the effects
      of H. pylori eradication therapy on the morphological and functional recovery of
      gastric antral and corpus D cells in patients with chronic gastritis during 6
      months of follow-up. PATIENTS AND METHODS: Forty consecutive, dyspeptic patients
      referred for endoscopy (31 with H. pylori infection and nine controls; mean age
      49 years; 17 men, 23 women) entered the study. All patients had histological
      signs of gastritis but no signs of peptic ulcer or gastric cancer. Antrum (n=8)
      and corpus (n=6) biopsy specimens were collected for routine histology,
      radioimmunoassay tissue somatostatin levels, immunohistochemistry and electron
      microscopy, prior to and 6 months after therapy. Basal plasma somatostatin levels
      were determined prior to eradication, plus 6 weeks and 6 months after therapy.
      Eradication therapy consisted of amoxicillin, metronidazole and omeprazole.
      RESULTS: Basal somatostatin plasma values in antral and corpus tissue were lower
      in infected patients than in the H. pylori-negative controls at the beginning of
      the study. A significant increase occurred after successful eradication therapy,
      together with an increase in the number of D cells in both regions. Changes in
      the D-cell ultrastructure in antral and corpus mucosa after eradication therapy
      suggest an increase in somatostatin synthesis and secretion. CONCLUSIONS: The
      structural and functional restoration of D cells following eradication therapy
      indicates possible recovery of the diseased mucosa.

PMID- 12811307
TI  - Altered cardia epithelial cell kinetics induced by Helicobacter pylori infection
      and gastro-oesophageal reflux disease: possible malignant potential?
AB  - BACKGROUND: The incidence of adenocarcinoma of the proximal stomach (cardia) is
      increasing. The pathophysiological processes underlying this trend are unclear.
      Normal cell turnover depends on cell proliferation being in balance with
      programmed cell death or apoptosis. It has been well documented that excessive
      proliferation potentiates the effects of any carcinogen that targets DNA. It is
      therefore accepted that excessive proliferation is a risk factor for subsequent
      neoplasia development. AIMS: To compare apoptosis and proliferation in normal
      cardia tissue, carditis, and cardia intestinal metaplasia, and to determine the
      effect of Helicobacter pylori infection and gastro-oesophageal reflux disease.
      METHODS: Biopsies from the cardia were obtained from consecutive dyspeptic
      patients and asymptomatic controls at the time of gastroscopy. Samples were
      assessed histologically and classified as normal, carditis, or cardia tissue with
      intestinal metaplasia. All samples were then examined, employing
      immunohistochemical techniques, for the presence of proliferating and apoptotic
      cells. RESULTS: A total of 76 histological specimens were examined. There was a
      statistical significant difference in the proliferation index between controls
      and both carditis and cardia intestinal metaplasia, and also between carditis and
      cardia intestinal metaplasia. In contrast, there was a significant increase in
      the apoptotic index for carditis compared with controls, while that of intestinal
      metaplasia did not differ from controls. As a result, comparison of the
      apoptotic/proliferation ratios for each group revealed that, for both carditis
      and cardia intestinal metaplasia, the apoptotic index/proliferation index ratio
      is reduced significantly compared with controls, but as a result of different
      mechanisms. CONCLUSION: This study demonstrates that individuals with carditis
      and cardia intestinal metaplasia have alterations in epithelial cell kinetics. In
      particular, it shows that there is a persistent imbalance between proliferation
      and apoptosis, which may represent malignant potential.

PMID- 12811308
TI  - Impedance characteristics of normal oesophageal motor function.
AB  - OBJECTIVE: To obtain detailed data about the correlation between oesophageal
      peristalsis and bolus transport for clinical oesophageal motility testing.
      METHODS: Oesophageal motility testing was performed in 25 healthy subjects by
      using the newly developed technique of concurrent impedancometry and manometry.
      Parameters of oesophageal motility and bolus transport as well as the correlation
      between transit and motility were analysed after swallowing saline or yogurt.
      RESULTS: Detailed data about bolus transport and oesophageal motility could be
      obtained during a single investigation step. Air was observed in front of the
      bolus in 76% of the swallows. Resting baseline impedance was significantly higher
      in the oesophagus than in the stomach (2832+/-118 Omega vs 688+/-119 Omega). The
      deglutitive impedance gradient was 222+/-26 Omega for saline and 482+/-38 Omega
      for yogurt. Bolus propagation velocity and bolus transit time as impedance
      parameters of bolus transport discriminated fluid from semisolid bolus (4.0+/-0.1
      cm/s vs 3.2+/-0.1 cm/s and 9.9+/-0.2 s vs 11.5+/-0.2 s, for saline vs yogurt),
      while contraction wave amplitude as a manometry parameter of oesophageal motor
      function did not (91.4+/-7.5 mmHg vs 80.7+/-9.4 mmHg, for saline vs yogurt).
      There was a poor correlation between bolus propagation velocity and contraction
      wave amplitude. CONCLUSIONS: Impedance parameters of normal oesophageal motor
      function have been characterized. Impedancometry and manometry provide different
      but complementary data about oesophageal motor function. Concurrent
      impedancometry and manometry allows detailed monitoring of oesophageal motility
      and bolus transit, which may open new perspectives for comprehensive oesophageal
      motility testing.

PMID- 12811309
TI  - Histopathology of the gastric oxyntic mucosa in two different patient groups
      during long-term treatment with omeprazole.
AB  - OBJECTIVES: Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter
      pylori infection, dose and duration of omeprazole treatment may separately, or in
      combination, influence the proliferation of enterochromaffin-like (ECL) cells and
      parietal cell changes in gastric mucosa. To assess the effects of these variables
      comparisons were carried out in patients with the acid related Zollinger-Ellison
      syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and
      gastro-oesophageal reflux disease. METHODS: Twenty-five patients with PSS and 16
      patients with ZES were included and received continuous omeprazole treatment for
      a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with
      endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients
      were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were
      titrated to a basal acid output of zero H+. RESULTS: Changes towards diffuse and
      linear ECL cell hyperplasia were observed in 41% of the PSS patients.
      Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes
      towards linear and micronodular hyperplasia were observed in all patients. Two
      patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also
      parietal cell changes were more pronounced in the ZES group than in the PSS
      group. CONCLUSIONS: In patients without intrinsic acid hypersecretion and
      hypergastrinaemia significant proliferation of ECL cells is not an issue
      irrespective of gastric mucosal inflammation, omeprazole dose, duration of
      treatment and acid inhibition. The level of gastrin secretion and high plasma
      gastrin appear to accelerate ECL cell proliferation and parietal cell changes
      possibly influenced by chronic gastritis and H. pylori infection.

PMID- 12811310
TI  - Intra-oesophageal pH profiles and pharmacokinetics of pantoprazole and
      esomeprazole: a crossover study in patients with gastro-oesophageal reflux
      disease.
AB  - AIM: To compare the effect of pantoprazole and esomeprazole on intra-oesophageal
      pH and investigate their pharmacokinetics in patients with symptomatic gastro
      oesophageal reflux disease (GORD). METHODS: Double-blind, randomized, two-period
      crossover study. Caucasian men with symptomatic GORD (n=48) were selected on the
      basis of clinical records of typical GORD symptoms, confirmed by a pathological
      reflux time (oesophageal pH<4 for > or =6% of the time). They received oral
      pantoprazole 40 mg once daily (od) or esomeprazole 40 mg od for seven days.
      Continuous 24 h oesophageal pH-metry was performed at baseline and day 7.
      Evaluations included: pre- and post-treatment differences in the percentage of
      time with pH<4.0 and <3.0 between baseline and day 7; area under the curve (AUC),
      Cmax, and T(1/2); point estimates and 90% confidence intervals (CI) on days 1 and
      7, calculated for ratios of the AUC and Cmax. RESULTS: Both drugs decreased the
      mean total number of reflux episodes and reduced the percentage of reflux time
      within 24 h to <3%. No pathological reflux was detectable after repeated
      administration of either drug. The 90% CI were within the predefined range at all
      time points; thus, equivalence of pantoprazole and esomeprazole was concluded.
      For pantoprazole, Cmax and AUC were unchanged on day 7 vs day 1, confirming its
      high and constant bioavailability. For esomeprazole, Cmax and AUC were increased
      on day 7 vs day 1 by 80% and 50%, respectively, indicating low initial
      bioavailability. No clinically relevant side effects were seen for either drug.
      CONCLUSION: Pantoprazole and esomeprazole have equivalent effect on oesophageal
      pH, since no pathological reflux was detected after treatment with either drug.
      For esomeprazole, the Cmax and AUC increased after multiple dosing; for
      pantoprazole the pharmacokinetics were predictable and independent of the number
      of administered doses.

PMID- 12811311
TI  - Immunoglobulin E production in chronic pancreatitis.
AB  - OBJECTIVES: Serum immunoglobulin E (IgE) was investigated in patients with
      chronic pancreatitis in order to elucidate possible disease mechanisms linking
      pancreatitis, adverse reaction to foods and allergy. DESIGN AND METHODS: Serum
      IgE was analysed in 86 non-atopic patients with advanced chronic pancreatitis and
      54 non-atopic controls. IgE detection was performed by enzyme-linked
      immunofluorescence. RESULTS: Mean IgE levels (+/- standard error of mean) in
      chronic pancreatitis patients (286.1+/-49 kU/l) were found to be significantly
      elevated compared to controls (67.7+/-11 kU/l; P<0.0001). Normal IgE levels (<100
      kU/l) were present in 40/54 control patients (74.1%), but only 39/86 pancreatitis
      patients (45.3%). Of the patients with chronic pancreatitis, 47/86 (54.6%) had
      clearly elevated IgE levels of >100 kU/l and their IgE values did not show a
      Gaussian distribution. However, nine-fold higher IgE levels were found in chronic
      pancreatitis patients with alcohol consumption of >25 g/day and exocrine
      insufficiency (915.5+/-240 kU/l) than in pancreatitis patients with normal
      exocrine function and no alcohol consumption (103.4+/-43 kU/l; P<0.001).
      Moreover, acute episodes of chronic pancreatitis were found to increase serum IgE
      levels. CONCLUSIONS: In patients with chronic pancreatitis, serum IgE production
      is markedly enhanced, especially during acute inflammatory episodes or when
      alcohol is consumed. Since abstinence from alcohol and pancreatic enzyme
      substitution are associated with clearly lower IgE levels, it may be concluded
      that pancreatic insufficiency with reduced nutrient digestion and alcohol
      consumption stimulate IgE production. This finding gives rise to the speculation
      that, apart from pancreatic inflammation, cross-linking of IgE with alimentary or
      other antigens might be involved in the pathophysiology of a sub-population of
      patients with chronic pancreatitis and manifest pancreatic insufficiency.

PMID- 12811312
TI  - Magnetic resonance cholangiopancreatography versus endoscopic retrograde
      cholangiopancreatography in the diagnosis of choledocholithiasis.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) has become
      established as the gold standard in imaging of the biliary tree. Recently,
      magnetic resonance cholangiopancreatography (MRCP) has been introduced as a new,
      non-invasive imaging modality for the detection of bile-duct stones and other
      pathology related to the biliary tract and pancreas. The aim of this study was to
      determine how MRCP compared with ERCP in the diagnosis of choledocholithiasis.
      DESIGN AND METHODS: A prospective study of 133 patients referred for either ERCP
      or MRCP was carried out to compare the results of both these methods in
      determining the presence of choledocholithiasis. RESULTS: 18 patients were
      excluded from the analysis: ERCP was unsuccessful in eight of these patients and
      MRCP was not possible in the remaining 10 patients. There were six false negative
      results with MRCP; in five of these the calculi were less than 5 mm in diameter.
      MRCP showed a sensitivity of 84%, specificity of 96%, positive predictive value
      of 91%, negative predictive value of 93% and diagnostic accuracy of 92% when
      compared to ERCP as the gold standard. CONCLUSIONS: MRCP has high sensitivity and
      high specificity for stones greater than 5 mm in diameter and should be performed
      in preference to ERCP as the first-line investigation in patients with gallstones
      and abnormal liver function tests in the elective setting. Adoption of this
      guideline at our institution would result in a 9% reduction in the number of
      ERCPs performed.

PMID- 12811313
TI  - Ulcerative colitis, primary sclerosing cholangitis and coeliac disease: two cases
      and review of the literature.
AB  - The combination of ulcerative colitis, sclerosing cholangitis and coeliac disease
      is unusual. The two cases described here illustrate that the investigation and
      management of such patients can be difficult. Other diagnoses should be
      considered when a patient with a known pathology fails to respond to treatment.
      Review of the literature suggests an increased malignant potential in these
      patients. We conclude that patients with a combination of ulcerative colitis,
      sclerosing cholangitis and coeliac disease should undergo annual colonoscopic
      surveillance. In those with clinical deterioration and weight loss, early liver
      and bowel imaging should be carried out.

PMID- 12811314
TI  - The role of HBeAg seroconversion in acute exacerbation of liver disease with
      termination of hepatitis B and D virus infection in a chronic hepatitis D patient
      during alpha-interferon therapy.
AB  - We report a severe flare-up in a chronic hepatitis patient due to dual infection
      with hepatitis B and D viruses during alpha-interferon therapy. Pre-treatment,
      the patient had detectable levels of both viruses. After 9 months of therapy, an
      alanine aminotransferase flare with acute hepatic decompensation was detected.
      Alpha-interferon was discontinued and lamivudine (100 mg once daily) was started,
      after which the patient reversed slowly. Hepatitis B early antigen (HBeAg)
      seroconversion with hepatitis B virus-DNA clearance was observed 1 month after
      the flare; 15 months later, the patient had persistently normal alanine
      aminotransferase levels with negative results for both serum hepatitis B virus
      DNA and hepatitis D virus-RNA. In conclusion, liver disease may be exacerbated
      during interferon therapy in patients with chronic hepatitis D who are also
      positive for hepatitis B surface antigen (HBsAg) and HBeAg. Therefore, extra care
      in monitoring should be considered and strict follow-up is recommended, since
      clearance of hepatitis D may occur after HBeAg seroconversion in coinfected
      patients. Lamivudine may be administered early in hepatitis D-RNA/HBsAg-positive
      patients at high risk of liver failure once a severe flare-up occurs during
      interferon therapy.

PMID- 12811315
TI  - Pseudoachalasia caused by pancreatic carcinoma.
AB  - Secondary achalasia or pseudoachalasia is mostly caused by gastric or oesophageal
      carcinoma. Here we report a case of pseudoachalasia caused by a pancreatic tumour
      invading the cardiac region. A 66-year-old man with a 2-month history of
      dysphagia and weight loss showed no abnormalities on upper gastrointestinal
      endoscopy and computed tomography scan, but had no swallow-induced relaxation on
      oesophageal manometry. Based on the patient's history and oesophageal manometry
      findings, further investigation was performed to exclude pseudoachalasia.
      Endoscopic ultrasonography showed abnormalities in the cardiac region, but large
      endoscopic biopsies showed no malignancy. A laparotomy was performed, which
      revealed a large, irresectable tumour originating from the pancreatic corpus
      region and expanding into the gastric cardia region. This case illustrates that a
      pancreatic tumour invading the cardiac region may present as pseudoachalasia.

PMID- 12811316
TI  - Cure of Barrett's carcinoma by ifosfamide chemotherapy.

PMID- 12811317
TI  - Is liver biopsy necessary for hepatitis C virus carriers with persistently normal
      aminotransferase levels?

PMID- 12811318
TI  - Strategic planning: drafting your roadmap to success.

PMID- 12811319
TI  - Development and psychometric testing of the infant colic scale.
AB  - Novice researchers, when confronted with a clinical problem they want to study,
      are admonished by more experienced researchers to search the literature for an
      instrument that already has established reliability and validity, fits the
      problem of study, or that can be easily adapted. Sometimes, however, there is no
      such instrument available so the researcher has to develop a new instrument. The
      purpose of this article is to describe the steps required to develop and
      psychometrically test a new instrument. A new instrument, the Infant Colic Scale,
      is used as an example.

PMID- 12811320
TI  - Bowel preparation comparison: flavored versus unflavored colyte.
AB  - Patients undergoing colonoscopy who have poor bowel cleansing must undergo
      repeated colon lavage and procedure, resulting in the possibility of additional
      discomfort and risk. Patient compliance with the necessary 4 liters of colon
      lavage fluid is essential. At our facility, the current colon lavage solution is
      unflavored and most patients complain about the taste. These are the patients who
      are likely to have poorly cleansed bowels. Patient preference for flavor of
      lavage is not known. A randomized controlled trial of 130 patients was undertaken
      to learn whether Colyte flavor made a difference in bowel cleansing. Results
      showed flavor made no difference in bowel cleansing (chi2 = 0.064, p =.96, NS);
      successful cleansing occurred in 75% (n = 45) of patients who received flavored
      and 76% (n = 53) who received unflavored Colyte. Results suggest flavor is not a
      factor in patients' completion of the prep nor cleansing effectiveness. As
      unflavored Colyte costs less than flavored, cost savings can result from
      continuing use of unflavored Colyte. While this clinical trial did not answer the
      dilemma about how to improve colon preparation, the staff's process of conducting
      nursing research inspired critical thinking and innovative problem-solving.
      Patients who are undergoing a colonoscopy are required to do a bowel cleansing
      the day before the procedure. Without proper bowel cleansing, colonic lesions
      such as polyps, neoplasms, and arteriovenous malformations (AVMs) may go
      undetected by being covered with small particles of stool ( Cohen et al., 1994).
      Poor bowel cleansing results in the need for repeat colon preparation and repeat
      procedure, which pose risk and discomfort for the patient and cost for the staff
      and institution. Done under moderate sedation, colonoscopy poses potential
      cardiac risks and respiratory problems for the patient. In addition, the
      endoscopy procedure itself could cause perforation and bleeding. Avoiding repeat
      procedures because of failed colonic preparation is, therefore, essential for
      patient safety and organization cost. Optimally, completing the colon prep
      solution results in adequate bowel cleansing. Prep flavor was theorized to be a
      possible cause of noncompliance. The purposes of this study were to determine
      whether patients' preferred prep solution would yield better compliance with the
      colon lavage solution and whether the improved compliance results in an
      adequately prepared bowel.

PMID- 12811321
TI  - Endoscope disinfection by ortho-phthalaldehyde in a clinical setting: an
      evaluation of reprocessing time and costs compared with glutaraldehyde.
AB  - Ortho-phthalaldehyde provides high-level disinfection in 12 minutes at room
      temperature (20 degrees C). To determine whether the endoscopy unit at
      Massachusetts General Hospital could cost-effectively increase endoscope
      throughput and decrease delayed procedures while maintaining biocidal efficacy
      with heavy use, ortho-phthalaldehyde solution (0.55% w/v) was used for high-level
      disinfection in place of glutaraldehyde in the unit's five automatic endoscope
      reprocessors. During this 38-day study, 1,839 endoscopes were processed in 1,201
      cycles. Each machine ran an average of 80 disinfection cycles in each of three
      consecutive periods. The shorter disinfection time of ortho-phthalaldehyde (12
      minutes) resulted in an average savings of 53 hours in disinfection time per
      study period for the five processors when compared with glutaraldehyde's 20
      minute disinfection time.Ortho-phthalaldehyde costs more per gallon than
      glutaraldehyde ($31.03 versus $13.20). This higher cost would be offset, however,
      by additional time savings resulting from the fact that compared with
      glutaraldehyde, ortho-phthalaldehyde is faster-acting and a mixing and activation
      step is not required. In addition, testing prior to each cycle verified that
      despite heavy use, ortho-phthalaldehyde solution remained efficacious, lasting
      through an average of 80 cycles, whereas glutaraldehyde only lasts for an average
      of 40 cycles. Test strips showed the concentration of ortho-phthalaldehyde in the
      reprocessors remained above the minimum effective concentration for the entire 14
      day maximal reuse period. Additional microbiological efficacy testing of spent
      solution diluted to its minimum effective concentration demonstrated the solution
      remained tuberculocidal in tests with Mycobacterium bovis.

PMID- 12811322
TI  - A study of the relationships between self-evaluation of physical condition and
      perception of difficulties of life in ulcerative colitis patients.
AB  - This study was conducted to elucidate factors that influence the self-evaluation
      of physical condition and perception of difficulties of life in ulcerative
      colitis patients. A survey and clinical examination were carried out in 171
      outpatients with ulcerative colitis. Self-evaluation of physical condition was
      assessed according to a five-grade system. Perception of difficulties of life was
      assessed using a scale developed by the authors and others. Physical condition of
      patients was assessed according to their disease state, disease symptoms, and
      nutritional state. Additional related factors such as mental condition,
      demographic attributes, and psychosocial states were also investigated. Multiple
      regression analyses was used to assess the relationships among variables and
      showed that perception of difficulties of life and disease symptoms were the main
      explanatory factors for the self-evaluation of physical condition. Perception of
      difficulties of life was comprised of physical and mental conditions, the latter
      being further influenced by the patients' psychosocial state.

PMID- 12811323
TI  - Evidence-based practice: gastroesophageal reflux disease.

PMID- 12811324
TI  - Leading the way: development of an interdisciplinary pharmaceutical outcomes
      management program.

PMID- 12811325
TI  - Patient perspective: Debbie's journal.

PMID- 12811326
TI  - Research in practice: evaluating an instrument for research.

PMID- 12811327
TI  - Colon cancer.

PMID- 12811358
TI  - Hypothesis: a single clinical trial plus causal evidence of effectiveness is
      sufficient for drug approval.

PMID- 12811359
TI  - Exposure-response analysis of pregabalin add-on treatment of patients with
      refractory partial seizures.
AB  - OBJECTIVE: Our objectives were to describe the exposure-response relationship of
      pregabalin add-on treatment for refractory partial seizures after multiple dosing
      in patients and to identify the factors that influence this relationship.
      METHODS: A mixed-effects model was used to characterize the relationship between
      monthly seizure frequency over a 3-month period and pregabalin daily dose (0, 50,
      150, 300, and 600 mg) as add-on treatment in 3 double-blind, parallel-group
      studies in patients with refractory partial seizures (N = 1042). Seizure
      frequency was modeled as a Poisson process expressed as a function of baseline
      seizures, drug treatment, placebo effect, and subject-specific random effects.
      The model included a parameter that partitioned the population into
      subpopulations with respect to response. RESULTS: Seventy-five percent of
      patients showed an asymptotic decrease in seizure frequency with increasing doses
      of pregabalin, whereas 25% did not demonstrate a significant decrease in seizure
      frequency from baseline. In patients who demonstrated a dose-related decrease in
      seizure frequency from baseline, the maximal percentage of seizure reduction from
      baseline was 100% for women and 80% for men, with a 186-mg daily dose decreasing
      seizures on average to 50% of maximum. Age, race, and menopausal status did not
      significantly affect seizure frequency. CONCLUSION: Pregabalin add-on treatment
      demonstrates a dose-response relationship in 3 out of 4 patients with refractory
      partial seizures. A dose of 186 mg pregabalin daily is expected to decrease the
      seizure rate by 50% of maximum from baseline. Age, race, and menopausal status of
      women did not affect the dose-response relationship.

PMID- 12811360
TI  - Antagonism by methotrexate on mercaptopurine disposition in lymphoblasts during
      up-front treatment of acute lymphoblastic leukemia.
AB  - BACKGROUND: Methotrexate is postulated to enhance mercaptopurine activation to
      thioguanine (INN, tioguanine) nucleotides, but the interaction has never been
      studied in vivo in cancer cells. METHODS: We investigated the effect of
      methotrexate on mercaptopurine disposition in plasma and leukemic blasts during
      up-front treatment of 233 children with newly diagnosed acute lymphoblastic
      leukemia. Children were randomized to receive intravenous mercaptopurine (1
      g/m(2) over a 6-hour period) or to receive methotrexate (low dose, 6 oral doses
      of 30 mg/m(2), or high dose, 1 g/m(2) intravenously), followed by intravenous
      mercaptopurine. All combinations have been previously used in frontline trials
      for acute lymphoblastic leukemia. RESULTS: Compared with mercaptopurine alone,
      methotrexate resulted in higher plasma mercaptopurine concentrations (30.3 +/-
      14.7 micromol/L versus 23.5 +/- 18.0 micromol/L, P <.001) but, conversely, a 13
      fold lower thioguanine nucleotide concentration (0.57 +/- 0.66 pmol/5 x 10(6)
      cells versus 7.4 +/- 15.2 pmol/5 x 10(6) cells, P <.001) in bone marrow leukemic
      lymphoblasts. Methotrexate was also associated with higher plasma hypoxanthine
      concentrations compared with those of patients given mercaptopurine alone (8.7 +/
      13.5 micromol/L versus 3.8 +/- 2.5 micromol/L, P =.029). The percentage change
      in leukocyte counts measured over a 3-day period showed that mercaptopurine alone
      had little effect (mean decrease, 20% +/- 33%). In contrast, despite causing
      lower intracellular thiopurine active metabolite concentrations, methotrexate
      produced a greater decrease in leukocyte counts (mean, 53% +/- 35%) compared with
      those in patients receiving mercaptopurine alone (P <.0001). CONCLUSION: These
      pharmacologic findings in the target tissue are consistent with the recently
      demonstrated lack of clinical benefit of intravenous mercaptopurine in
      combination with methotrexate. We conclude that, in the setting of newly
      diagnosed acute lymphoblastic leukemia, methotrexate antagonizes thiopurine
      metabolite disposition in leukemic blasts after intravenous mercaptopurine.

PMID- 12811361
TI  - The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes.
AB  - OBJECTIVES: Our objectives were (1) to determine whether the drugs caffeine,
      losartan, omeprazole, debrisoquin (INN, debrisoquine), and quinine can be given
      simultaneously in low doses as a cocktail for the phenotyping of cytochrome P450
      (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4, respectively, and (2) to design an
      administration schedule to give as few sampling occasions as possible. METHODS:
      Twenty-four subjects were given oral doses of 100 mg caffeine, 25 mg losartan, 20
      mg omeprazole, 10 mg debrisoquin, and 250 mg quinine on separate days. After a
      washout period of at least 4 days, all drugs were given simultaneously except for
      quinine, which was given 8 hours after the other drugs. Blood and urine samples
      were collected to determine parent drug and metabolite concentrations for
      assessment of phenotyping indices. Any difference between both single and
      cocktail doses was tested on a log-normal distribution. RESULTS: The phenotypic
      indices of CYP1A2 (paraxanthine/caffeine in 4-hour plasma), CYP2C9 (losartan/E
      3174 [metabolite of losartan] in 0- to 8-hour urine), CYP2C19 (omeprazole/5
      hydroxyomeprazole in 3-hour plasma), and CYP3A4 (quinine/3-hydroxyquinine in 16
      hour plasma) were not significantly changed when probe drugs were administered
      alone compared with together, although a tendency toward higher concentrations of
      losartan was seen during simultaneous administration (95% confidence interval,
      0.51-1.002; P =.051). The CYP2D6 phenotypic index (debrisoquin/4
      hydroxydebrisoquin in 0- to 8-hour urine) was significantly changed when drugs
      were given together (95% confidence interval, 0.45-0.87; P =.007), indicating an
      inhibition of the debrisoquin metabolism. The within-subject coefficients of
      variation (8%-25%) were much lower than the between-subject coefficients of
      variation (34%-79%). CONCLUSIONS: The administration of drugs together suggests
      an inhibition of debrisoquin metabolism caused by the concurrent drugs given. By
      separating debrisoquin from the other cocktail drugs, this method is likely to be
      used as a tool to phenotype the enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and
      CYP3A4 with only 2 urinary collections and 2 blood-sampling occasions.

PMID- 12811362
TI  - Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4
      activity: comparison with grapefruit juice.
AB  - OBJECTIVES: Our objective was to assess the importance of bergamottin in drug
      interactions through comparisons between grapefruit juice and lime juice and the
      potential for drug interactions with red wine. METHODS: Bergamottin content and
      in vitro reversible/irreversible inhibition of cytochrome P450 (CYP) 3A4
      monooxygenase activities were determined for grapefruit and lime juices. The oral
      pharmacokinetics of felodipine and its primary metabolite (dehydrofelodipine)
      were determined with 250 mL of grapefruit juice, one quarter-strength lime juice,
      red wine, or water in a randomized crossover study. RESULTS: Bergamottin
      concentrations in grapefruit and lime juices were 25 and 100 micromol/L,
      respectively. For reversible inhibition, log volume-residual CYP3A4 activity
      relationships for grapefruit and lime juices had negative linear slopes that were
      parallel. The curve for grapefruit juice was 4.0-fold right-shifted, as compared
      with that for lime juice. For irreversible inhibition, the curves for grapefruit
      and lime juices were 4.0- and 1.4-fold left-shifted, as compared with those for
      reversible inhibition, respectively. Grapefruit juice increased the mean
      felodipine area under the plasma concentration-time curve (AUC) (mean +/- SE, 55
      +/- 9 nmol. h/L versus 29 +/- 6 nmol. h/L; P <.05) and the plasma peak drug
      concentration (16 +/- 3 nmol/L versus 8 +/- 2 nmol/L, P <.05) and decreased the
      dehydrofelodipine/felodipine AUC ratio compared with those of water. One quarter
      strength lime juice did not alter mean values. However, the changes in individual
      felodipine AUC after grapefruit juice and lime juice correlated (r(2) = 0.95)
      with a low slope (0.36). One quarter-strength lime juice more than doubled
      felodipine AUC and plasma peak drug concentration in 2 subjects. Red wine
      prolonged mean felodipine time to plasma peak drug concentration. Felodipine
      concentrations were low and peaked abruptly in 4 subjects. Adverse effects
      occurred in 1 subject. CONCLUSIONS: Bergamottin and reversible inhibition are not
      the primary substance and mechanism responsible for inhibition of CYP3A4 activity
      clinically. Red wine can cause dose dumping of extended-release felodipine in
      certain individuals.

PMID- 12811363
TI  - Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin
      renal clearance.
AB  - BACKGROUND: Gemfibrozil increases the plasma concentrations of active acid forms
      of cerivastatin, lovastatin, and simvastatin. Pravastatin pharmacokinetics
      differs from those of these 3 statins, which are extensively metabolized. Our aim
      was to study the effects of gemfibrozil on the pharmacokinetics of pravastatin.
      METHODS: A randomized, placebo-controlled, 2-phase crossover study was carried
      out. Ten healthy volunteers took gemfibrozil (1200 mg/d) or placebo for 3 days.
      On day 3, each subject ingested a single 40-mg dose of pravastatin. The
      concentrations of pravastatin and gemfibrozil in plasma and the cumulative
      excretion of pravastatin into urine were measured up to 24 hours. RESULTS: During
      the gemfibrozil phase, the mean total area under the plasma concentration-time
      curve (AUC) of pravastatin from 0 hours to infinity was 202% (range, 40%-412%) of
      the corresponding value during the placebo phase (P <.05), but there was no
      difference in the half-life between the phases. The renal clearance of
      pravastatin was reduced from 25 L/h to 14 L/h by gemfibrozil (P <.0001), but the
      cumulative excretion of pravastatin into urine did not change significantly. The
      increase in the AUC of pravastatin from 0 to 24 hours correlated significantly
      with the decrease in the renal clearance of pravastatin (r = 0.72, P =.02).
      However, the change in renal clearance was only a minor contributor to the
      increase in pravastatin AUC. CONCLUSIONS: Gemfibrozil increases plasma
      concentrations of pravastatin. This is partly but not solely the result of the
      reduced renal clearance of pravastatin. The increase in pravastatin AUC from 0
      hours to infinity by gemfibrozil may represent an interference with a transport
      protein.

PMID- 12811364
TI  - Transiently altered acetaminophen metabolism after liver transplantation.
AB  - BACKGROUND AND OBJECTIVES: Acetaminophen (INN, paracetamol) is metabolized to N
      acetyl-p-benzoquinone imine (NAPQI), a hepatotoxic metabolite, predominantly by
      cytochrome P450 (CYP) 2E1. Alterations in drug metabolism occur after organ
      transplantation. This study was designed to characterize acetaminophen
      disposition during the first 6 months after liver transplantation. METHODS:
      Thirteen liver transplant patients received an oral dose of acetaminophen (500
      mg) on days 2, 10, 90, and 180 after transplantation. Serial blood samples were
      collected for 8 hours, and urine was collected for 24 hours. Liver biopsy
      specimens were obtained from the donor liver during transplantation (day 0) and
      on days 10, 90, and 180 after transplantation. RESULTS: There were significant
      time-dependent changes in acetaminophen metabolism after liver transplantation.
      When day 2 and day 10 were compared with day 180, the respective mean urinary
      recovery was 137% and 81% higher for thioether conjugates derived from NAPQI (P
      =.0002 and P =.01, respectively); 31% and 22% lower for acetaminophen sulfate (P
      =.0006 and P =.008, respectively); and 22% and 27% lower for acetaminophen
      glucuronide (P =.05 and P =.004, respectively). Metabolite formation clearances
      changed in concordance with the fractional urinary recovery. It was surprising
      that hepatic CYP2E1 content on day 10 after transplantation was only 20% higher,
      on average, than that found on day 180 (not significant). In contrast, hepatic
      CYP3A4 content was 984% higher, on average, when tissue from days 10 and 180 was
      compared after transplantation (P =.007). CONCLUSIONS: Increased recovery of
      acetaminophen thioether conjugates during the first 10 days after liver
      transplantation was a result of impaired glucuronidation and sulfation and
      enhanced NAPQI formation.

PMID- 12811365
TI  - Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for
      pravastatin pharmacokinetics.
AB  - OBJECTIVE: Our objective was to quantitate the contribution of the genetic
      polymorphisms of the genes for 2 human organic anion transporters-organic anion
      transporting polypeptide C (OATP-C) and organic anion transporter 3 (OAT3)-to the
      pharmacokinetics of pravastatin. METHODS: Genetic polymorphisms were screened by
      polymerase chain reaction-single-strand conformation polymorphism analysis, after
      sequencing with deoxyribonucleic acid obtained from 120 healthy volunteers. To
      examine whether polymorphisms in these 2 genes of interest alter transport
      activity, we conducted a clinical study (n = 23) with pravastatin as a selective
      probe drug. RESULTS: Among 120 healthy individuals, 5 nonsynonymous variants and
      1 nonsynonymous variant were observed in the OATP-C and OAT3 genes, respectively.
      The polymorphisms in the OAT3 gene did not appear to be associated with changes
      in renal and tubular secretory clearance. In contrast, the OATP-C variants were
      associated with differences in the disposition kinetics of pravastatin. Subjects
      with the OATP-C*15 allele (Asp130Ala174) had a reduced total and nonrenal
      clearance, as compared with those with the OATP-C*1b allele (Asp130Val174);
      nonrenal clearance values in *1b/*1b (n = 4), *1b/*15 (n = 9), and *15/*15 (n =
      1) subjects were 2.01 +/- 0.42 L. kg(-1). h(-1), 1.11 +/- 0.34 L. kg(-1). h(-1),
      and 0.29 L. kg(-1). h(-1), respectively, and the difference between *1b/*1b and
      *1b/*15 subjects was significant (P <.05). CONCLUSION: Certain commonly occurring
      single-nucleotide polymorphisms in OATP-C, such as T521C (Val174Ala), are likely
      to be associated with altered pharmacokinetics of pravastatin. Large clinical
      studies are needed to confirm these observations.

PMID- 12811366
TI  - A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in
      patients receiving morphine.
AB  - We investigated the variation in the uridine diphosphate-glucuronosyltransferase
      2B7 (UGT2B7) gene in patients receiving patient-controlled analgesia with
      morphine. UGT2B7 was sequenced in phenotypic extremes (n = 12) of the
      distribution of morphine-6-glucuronide/morphine plasma ratios. A new -161C/T
      promoter variant was in complete linkage disequilibrium with the 802C/T variant
      and was more frequent in low glucuronidators (P =.039). Both variants were
      genotyped in all patients (n = 86), and complete linkage disequilibrium was
      confirmed. Trend analysis showed reduced morphine-6-glucuronide/morphine ratios
      in patients with T/T, C/T, and C/C genotypes (T/T > C/T > C/C) (P =.031).
      Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490
      ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range,
      18-3995 ng/mL) (P =.04). Morphine-6-glucuronide and morphine-3-glucuronide
      concentrations were significantly lower in C/C patients (median, 18 ng/mL; range,
      0-66 ng/mL; and median, 152 ng/mL; range, 30-434 ng/mL; respectively) compared
      with C/T and T/T patients combined (median, 43 ng/mL; range, 0-193 ng/mL; and
      median, 242 ng/mL; range, 33-1381 ng/mL; respectively) (P =.045 and P =.004,
      respectively). Interindividual differences in morphine glucuronidation may be the
      result of genetic variation in UGT2B7, and further studies are indicated.

PMID- 12811367
TI  - Discovery of a novel nonfunctional cytochrome P450 2D6 allele, CYP2D642, in
      African American subjects.

PMID- 12811368
TI  - [Forty years of experience with reconstructive operations for vasorenal
      hypertension].
AB  - Presented herein is an experience gained with 1356 reconstructions for vasorenal
      hypertension, performed at the RSCS, RAMS, over the period 1961 to 2001. The
      authors defined the criteria for the diagnosis of the given disease and the
      indications for surgical treatment. Also, the others demonstrate specific
      features of surgical treatment of patients presenting with different variants of
      renal artery lesion, provide the short- and long-term results of the main types
      of reconstructions accomplished for vasorenal hypertension, and emphasize the
      importance of the use of roentgenendovascular techniques. Based on the experience
      gained the conclusion is made about the advantages of surgical management versus
      conservative treatment methods.

PMID- 12811369
TI  - Vascular surgery in Europe.

PMID- 12811370
TI  - [Vasonit retard in the treatment of intermittent claudication in patients with
      obliterating diseases of the lower extremities].
AB  - This paper deals with an open no incomparable study of the efficacy of vasonit
      retard in the treatment of intermittent claudication in patients suffering from
      arterial pathology. The efficacy and tolerance of vasonit retard were
      investigated for two months at the A.V. Vishnevsky Institute of Surgery, RAMS,
      and at 20 vascular departments of Russia (Moscow, Sankt-Peterburg, Nizhny
      Novgorod, Perm, Yaroslavl, Volgograd, Omsk, Irkutsk, Chelyabinsk, Voronezh,
      Rostov-on-Don, Ekaterinburg). The study accrued 25 patients treated at the A.V.
      Vishnevsky Institute of Surgery, RAMS, and 348 patients treated on the basis of
      20 vascular departments of Russia, The basic criterion for inclusion into the
      study was the presence in the patient of intermittent claudication, corresponding
      to extremity ischemia, degree IIA end, IIB, according to the A.V.Pokrovsky
      classification. The treatment by vasonit retard was conducted outpatiently. The
      drug was administered in a daily dose of 1200 mg for 2 months. After treatment
      the ankle/brachial index along the posterior tibial artery and dorsalis pedis
      artery rose by over 17% in the group treated pt the Institute of Surgery and by
      over 21.5% in the group which participated in the multicenter study. The minimal
      pain-free distance increased by 60% and 115% respectively. The maximal pain-free
      distance rose by 37.7% and 98.4% respectively. A 25% abatement of the pain
      intensity (according to the pain score) was recorded in the group seen at the
      Institute of Surgery and a 36.1% pain abatement in the group included into the
      multicenter study. No complications leading to drug discontinuation were marked.
      Thus, talking into account the clinical evidence and the data supplied by
      instrumental diagnostic techniques, it is necessary to admit that vasonit retard
      is an effective drug for the treatment of patients suffering from intermittent
      claudication.

PMID- 12811371
TI  - [The treatment of critical lower limb ischemia using serotonin].
AB  - This paper describes the first experience with conservative treatment of 30 men
      suffering from critical lower limb ischemia using serotonin as an agent which may
      return endogenous vasomotility to normal and eliminate tissue hypoxia. Good and
      satisfactory results were obtained in 76% of patients (43 and 33% respectively).
      Deterioration followed by amputation was marked in 7% of patients. The removal or
      considerable abatement of rest pains was recorded in 86% (53 and 33%
      respectively) of cases. Amputation was performed in 10% of patients. It is
      recommended that serotonin adipinate should be included into multiraodality
      therapy of atherosclerotic critical lower limb ischemia. The use of the treatment
      method suggested will allow to improve the treatment results, to reduce the
      number and level of amputations, and to minimize the percentage of disability.

PMID- 12811372
TI  - Results of hospital bypass angiography in patients with coronary artery disease
      undergoing arterial and vein myocardial revascularization.
AB  - This paper analyzes the results of 94 coronary artery bypass grafts accomplished
      at the Department of Surgical Treatment of Concomitant Lesions of Coronary and
      Peripheral Arteries, A.N. Bakulev SCCVS, RAMS, in patients with coronary artery
      disease (CAD) provided control hospital bypass angiography over the period 1998
      to 2002. Control bypass angiography revealed thrombosis of 11.7% of vein and of
      1.5% of arterial grafts. The main causes of vein graft thromboses were: bypass
      grafting of small coronary arteries, that of the coronary arteries with so-called
      'immature' stenoses, and mediastinitis. The data presented herein evidence that
      hospital arterial bypass graft provides for a considerably higher percentage of
      competence versus vein bypass graft. Hospital bypass angiography is essentially
      safe while its findings allow to make a detailed analysis of complications
      whereby upgrading the efficacy of operations.

PMID- 12811373
TI  - Endovascular embolization of the hepatolienal vessels in the treatment of portal
      hypertension.
AB  - PURPOSE: to study the characteristics and variants of changes in the structure of
      celiac trunk and portal vein pool vessels, to define the tactics of most
      effective use of endovascular interventions in the treatment of portal
      hypertension. MATERIAL AND METHODS: the immediate and long-term results of
      angiographic studies and endovascular interventions are analyzed in 329 patients
      with portal hypertension induced by liver cirrhosis. The compensated stage of
      portal hypertension was identified in 62, subcompensated in 93 and decompensated
      in 174 patients. The patients underwent embolization of the splenic, left gastric
      and gastro-omental arteries, varices of the esophagus and cardial part of the
      stomach. In the long-term period, appropriate corrective medical endovascular
      interventions were performed in the event of the identification of recanalization
      of the previously embolized vessels and occurrence of the collateral pathways.
      RESULTS: after embolization of the splenic artery the positive shifts in blood
      readings, reduction of the splenic size, and abatement of ascites were revealed
      in the majority of cases. In the long-term period, the efficacy of the procedure
      diminished as a result of restoration of the lumen of the previously embolized
      vessels or development of the collaterals which demanded repeat endovascular
      intervention. The hospital lethality among patients with portal hypertension who
      had been provided endovascular interventions because of esophageal bleeding
      accounted for 29.8%, with the incidence of early recurrences being equal to 4.8%.
      The best results were obtained in a group of patients who had undergone
      embolization of bleeding gastroesophageal varices coupled with occlusion of the
      splenic artery for decompression and intraportal infusion therapy.

PMID- 12811374
TI  - [Endovascular embolization of arteriosinusoidal fistula with new coil type].
AB  - A case report for endovascular embolization of cerebral arteriosinusoidal fistula
      with new coil type is presented. Endovascular procedure enabled to avoid
      extensive surgical intervention and provided the evidence of its effectiveness
      for management of patients with cerebral arteriovenous malformations.

PMID- 12811375
TI  - Anatomic and hemodynamic changes in the inferior vena cava associated with
      prevention of pulmonary thromboembolism.
AB  - This paper analyzes the results of a multimodality instrumental study of the
      structural and functional properties of the inferior vena cava (IVC) in 173
      patients with acute venous thrombosis, who underwent different interventions
      aimed at pulmonary thromboembolism (PTE) prevention. Of these, 63% of patients
      were examined in the long-term period, within the time 2 to 36 months. 26% of
      patients were found to have variants of the anatomic structure of the IVC system,
      such as the doubling of the renal veins, ring-shaped structure or entry to the
      IVC at a distance exceeding 5 cm from each other. The paper also provides a
      detailed analysis of the hemodynamic parameters (maximal and minimal linear flow
      velocities in the IVC, time-averaged maximal linear flow velocities and their
      different indices) and of their changes as dependent on the type of interventions
      on the IVC. It has been established on the basis of the data obtained that
      endovascular catheter thrombectomy is the method for PTE prevention because it
      restores the IVC lumen and refines the regional hemodynamics. Cava filter
      implantation induces a rounded deformation and expansion of the infrarenal IVC up
      to 40.9% of the area of its cross section but exerts a minimal adverse effect on
      the flow. IVC plication leads to a slit-like deformation and a 12.9% stenosis of
      its lumen as well as to deceleration of the flow acquiring a turbulent character.

PMID- 12811376
TI  - [The role of endoscopic ligation of the perforating veins in the treatment of
      chronic venous insufficiency under conditions of the one-day surgery center].
AB  - The present work is concerned with the results of endoscopic ligation of the
      perforating veins (SEPS) in 179 patients with chronic venous insufficiency, class
      4-6, performed at the one-day surgery center. In patients suffering from
      varicosity, SEPS was accomplished in combination with phlebectomy in 52 (29.1%)
      patients. The second stage after phlebectomy involved the combination of SEPS
      with microsurgical reconstruction of the femoral vein valve. SEPS alone was
      provided to 89 (49.7%) patients suffering from postthrombotic disease. No life
      threatening complications or lethal outcomes were recorded. The postoperative
      events were observed in 20 (11.2%) patients. Good results were obtained in 128
      71.5%) patients, satisfactory in 42 (23.5%) and unsatisfactory in 9 (5%)
      subjects. The data obtained allow to regard SEPS as an effective, drastic and
      little traumatic technique which can be used successfully under conditions of the
      one-day surgery center.

PMID- 12811377
TI  - [The theory of lymphangion and current approaches to the pathogenesis, diagnosis
      and treatment of lymphedema of the lower extremities].
AB  - The paper describes the results of examination carried out by the Sankt-Peterburg
      school of lymphologists, pertaining to the structure, physiological properties
      and function of lymphangions responsible for active lymph transport. The problems
      of the pathogenesis, diagnosis and treatment of lymphedema of the lower
      extremities used in clinical practice are reviewed from the standpoint of the new
      theory. The data obtained as a result of the clinico-morphofunctional studies
      allowed to delineate the stages of lymphedema as dependent on the degree of
      lymphocytic structure and function integrity. Based on the aforesaid the new
      approaches to the diagnosis and selection of the treatment methods for lymphedema
      of the lower extremities have been formulated.

PMID- 12811378
TI  - [Diagnosis and treatment of postoperative recurrences of varicosity].
AB  - The aim of the present work was to study the causes of post-operative recurrences
      of varicosity and to define approaches to their optimal correction. Duplex
      scanning (DS) with Color Doppler Imaging of the blood flow was used to examine
      126 patients (136 extremities) with recurrences of varicosity. The patients were
      distributed according to the CEAP clinical classification. Altogether 76 patients
      (78) extremities with recurrences of varicosity were operated on. 27 persons
      received different variants of sclerotherapy including echoscleroobliteration.
      According to the DS data, the most frequently obtained finding in patients with
      recurrences of varicosity was identification of the perforating veins with
      valvular insufficiency, namely in 120 (or in 88.2%) extremities. The long stump
      of the greater saphenous vein (CSV) was discovered in 86 (63.2%) extremities, the
      long stump of the lesser saphenous vein (LSV) in 6 (4.4%), ectasia of LSV trunk
      was recognised in 20 (14.5%), incompetence of the valves of the sural veins in 12
      (8.8%) extremities. Incompetence of the valves of the deep veins was present in
      73 (53.6%) patients. No sources of pathological veno-venous runoff were
      identified in 12 (8.1%) cases. A good agreement was established between the
      incidence of valvular incompetence of the deep veins and the disease severity.
      The indications for surgical correction of valvular insufficiency were worked
      out. It has been demonstrated that sclero-obliteration is the method of choice in
      the treatment of the recurrences of varices. The long-term results of operations
      for recurrences of varicosity were followed up in 62 patients over the period of
      one to 15 years. Good and satisfactory results were obtained in 60 (96.8%) cases.
      The authors believe that the majority of varicosity recurrences arise from an
      inadequate assessment of the status of lower extremity venous bed as well as from
      technical and methodological faults of the operating surgeon. DS in an
      indispensable component of preoperative examination of patients with varicosity
      recurrences.

PMID- 12811379
TI  - [Phlebosclerosing treatment of lower extremity varicosity using the 'foam-form'
      technique].
AB  - This paper presents an experience gained with the treatment of 39 patients with
      lower extremity varicosity using a novel method of phlebosclerosing treatment,
      named the foam-form technique. The authors give a detailed description of the
      treatment modality, analyze the short- and long-term results. The conclusion is
      drawn that the given method is safe and effective. The emphasis is laid on the
      necessity of an objective evaluation of the collective experience with the use of
      the foam-form technique.

PMID- 12811380
TI  - Diagnosis of occlusive lesions of upper extremity arteries in patients with
      thromboangiitis obliterans.
AB  - The study accrued 84 patients suffering from thromboangiitis obliterans (TO)
      examined and treated at the A.V. Vishnevsky Institute of Surgery, RAMS, over the
      period 1988 to 2002. Based on the complaints on the part of the upper extremities
      the patients were distributed into four groups. Sixteen (19.1%) TO patients did
      not make any complaints on the part of the arms (degree I ischemia). Thirty-eight
      (45.2%) patients complained of numbness and paresthesia, chiefly of the tips of
      the fingers on both hands (degree II ischemia). Six (7.1%) persons complained of
      pains in the hands at physical exercise (decree III ischemia). Ulcers and
      necroses of the fingers were present in 24 (28.6%) patients (degree IV ischemia).
      The diagnostic procedures for arterial lesion of the upper extremities included
      laboratory investigations, duplex scanning of the great arteries, of the arteries
      of the hands, fingers and nail matrix, wide-field capillaroscopy, oxygen tension
      measurements, and angiography as well. Comparison of the clinical manifestations
      of arterial lesion of the upper extremities in TO patients to the data supplied
      by different research methods has revealed a direct correlation between the
      degree of ischemia and the pathomorphological as well as functional changes which
      increased as the ischemic syndrome was aggravated. As a result of the present
      work, there have been studied and systematized the criteria for the diagnosis of
      the degree of arterial lesion of the upper extremities in TO patients, based on
      the data, supplied by duplex scanning, capillaroscopy, measurements of
      transcutaneous oxygen tension and angiography. In addition, there has been
      studied the role of the humoral component of immunity in the delineation of
      inflammatory activity in patients with TO.

PMID- 12811381
TI  - [Roentgenosurgical treatment lesions of the brachiocephalic arteries].
AB  - Being the main cause of the lethality and permanent loss of work fitness,
      cerebrovascular diseases are assumed to be one of the most pressing problems of
      neurology and vascular surgery. It is to be noted that precisely stenotic and
      occlusive processes occurring in aortic arch branches induce ischemic lesions of
      the brain in half the cases. The multicenter cooperative randomized studies
      (MASCET, BCST, 'Veterans Affairs Cooperative Studies Program', VACT and ACAS)
      finalized the problem of the necessity of surgical treatment of patients with
      symptomatic and asymptomatic cerebrovascular insufficiency. However, despite the
      speedy progress in the cardiovascular surgery trend under consideration, a number
      of the fairly important problems remain unsolved. One of the important problems
      lies in the use of balloon angioplasty, stenting and thrombolysis of the
      precerebral arteries. The purpose of the study was to evaluate the results of
      roentrgenosurgical treatment of patients with hemodynamically significant lesion
      of the brachiocephalic arteries (BCA). Analysis was made of the treatment results
      in 19 patients aged 26 to 61 years. There were 13 (68.4%) men and 6 (31.6%)
      women. All the patients were provided different roentgenosurgical interventions
      on the BCA. Analysis of the results of roentgenosurgical interventions allowed to
      7 establish that in the given patient group, the neurologic syinptomatology
      regressed, to an appreciable measure, with an improvement in the quality of life.
      It is noteworthy that roentgenosurgical interventions considerably shortened the
      patients' stay at hospital. The advantages of the technology are as follows: a
      possibility of the contact with the patient for the whole period of the
      procedure, minimization of the time of brain hypovolemia due to instrumental
      examinations. However, the risk of intraoperative complications requires a
      careful selection of the patients and impeccable technical performance.

PMID- 12811382
TI  - Effect of carotid operations on regression of motor disorders in patients with a
      history of ischemic stroke.
AB  - This paper is concerned with an evaluation of the clinical effect of
      reconstructions on the brachiocephalic vessels in patients who suffered ischemic
      stroke. Altogether 143 patients with the above pathology were operated on. Of
      these, mild hemiparesis was present in 72 patients, moderate hemiparesis in 49,
      and severe hemiparesis was recognized in 17 subjects. The postoperative lethality
      accounted for 1.4% (2 subjects). Intraoperative development of repeated stroke
      was ascertained in three more subjects. The follow up of the operated patients
      lasted from three months to two years. In the postoperative period, a study was
      made of the time course of changes in motor pyramidal deficit. The study allowed
      the conclusion to be drawn that reconstructions on the brachiocephalic vessels
      are not only of preventive importance but also favour the elimination of motor
      disorders in patients who suffered ischemic stroke.

PMID- 12811383
TI  - [Surgical treatment policy during motor rehabilitation of patients with a single
      ischemic lower extremity].
AB  - Altogether 218 patients suffering from obliterating arterial diseases with
      unilateral postamputation defects (PAD) of the lower extremities and 13 patients
      with bilateral PAD were examined. A study was made of the data pertaining to the
      age, motivation for rehabilitation, occupational and social status, degree of
      social independence, and severity of circulatory disorders. The surgical
      treatment and rehabilitation policy for patients with unilateral PAD of the lower
      extremities was defined taking into account the social factory.

PMID- 12811385
TI  - [Successful correction with stent-graft of coronary artery rupture after
      angioplasty].
AB  - Rupture and perforation of coronary arteries complicate in average 0.5% of
      radiosurgical coronary interventions and often are accompanied by serious
      consequences and high mortality. According to-type of coronary perforation
      different methods of correction are used, ranging from conservative measures to
      urgent cardiosurgical interventions. Coronary stent-grafts with 'sandwich' type
      of construction ore composed from two metal stents and PTFE layer between them.
      Development of such stents enabled effective radioguided endovascular repair of
      coronary ruptures. The paper presents the first Russian experience of stout-graft
      implantation for coronary artery rupture occurred during direct stenting of
      proximal anterior descending artery and balloon angioplasty in distal segment.
      The rupture occurred probably because of wall fragility between affected segment
      and muscular bridge. Stent-graft JoStent 16 mm in length connected with 3-mm
      balloon was implanted with subsequent complete restitution of blood flow,
      resolution of pain syndrome and ECG normalization. Echocardiography in operative
      theatre and one day after surgery showed no intrapericardial fluid. Stent-graft
      devices for urgent implantation in cases of coronary rupture must be included
      into obligatory equipment of radiosurgical facilities.

PMID- 12811384
TI  - Surgical management of traumatic injuries to the tibial arteries.
AB  - Altogether 60 patients with traumatic injuries to the tibial arteries were
      entered into the study. Twenty-four patients presented with gunshot, 24 with stab
      and incised, 10 with contused and lacerated wounds, and 2 patients had blunt
      traumas. Thirty-nine patients were admitted to the clinic within the period as
      long as 8 hours since the time of wounding, 9 patients within 8 to 24 hours, and
      12 patients within the period as long as one to 15 days. 39 patients had been
      rendered first medical aid at other treatment institutions. It was established
      that prehospital diagnostic, tactic and technical errors had been made in 25 of
      the 39 patients. All the patients were distributed into three groups: group I
      (n=8) included patients with isolated injuries of one of the tibial arteries;
      group II (n=11) with injuries of two arteries and group III included patients
      with damage to all three arteries. In group I, circulation remained made for
      irrespective of the times of ischemic state existence. In groups II and III, all
      the patients demonstrated circulatory decompensation. Surgical management
      depended on the severity of the general condition and the degree of limb
      ischemia. Primary amputation was indicated to 11 (18.3%) patients (humid gangrene
      was diagnosed in 5 patients, severe trauma with major defects of soft tissues and
      bone fractures in 6 patients). The remaining 49 victims underwent different
      surgical interventions such as ligation of the vessel at injury to one artery
      (23); revascularization (22); fasciotomy, hematoma evacuation and reposition of
      the bones in an isolated form (4). Five (10.2%) patients required secondary
      amputation. Beneficial results with complete circulatory compensation were
      obtained in 44 (73,3%) patients. The overall amputation rate accounted for 26.6%.

PMID- 12811386
TI  - [Surgical treatment of abdominal aortic aneurysm in a patient with a horseshoe
      kidney (a case report)].
AB  - This paper describes a clinical case of the treatment of a patient with
      associated abdominal aortic aneurysm and a horseshoe kidney. Examination revealed
      type II blood supply of the horseshoe kidney according to Crawford. The operation
      was performed from thoraco-phreno-lumbotomy on the left. During operation, we
      ligated the accessory renal artery with a good retrograde blood flow, branching
      out just from the aneurysmal sac. Examination carried out in the early and long
      term postoperative period did not discover renal malfunction as shown by
      laboratory and radionuclide research methods.

PMID- 12811387
TI  - [Directed therapy in complex treatment of lower limb diabetic angiopathy].
AB  - Clinical efficiency of directed therapy was assessed for 312 patients with distal
      type of lower limb diabetic angiopathy. Methods of directed therapy included
      indirect electrochemical detoxication, hemosorption and their combination. It was
      shown that while successful rate of conventional conservative therapy does not
      exceed 50%, hemosorption and indirect electrochemical detoxication can increase
      this rate by 5-35%, depending on the initial severity of lower limb ischemia.
      Directed therapy improves peripheral circulation and attenuates regional toxemia.
      Optimal results were achieved for combination of hemosorption and indirect
      electrochemical detoxication: treatment was effective for 87% of patients with 2
      grade disease and for 73% - with 3-grade. One can speculate that synergic
      clinical effect may be attributed to functional normalization of antioxidant
      system. In conclusion, advantages of directed therapy comparing with conventional
      conservative treatment lie in its higher efficiency and prolonged therapeutic
      effect.

PMID- 12811388
TI  - Peripheral macrohemodynamics in patients with lower limb arteriosclerosis
      obliterans and type II diabetes mellitus.
AB  - The paper presents characteristic features of lower limb atherosclerotic lesions
      in patients with diabetes mellitus: more prominent calcification of vascular wall
      (involving media), frequent involvement of distal vascular segments and a
      symmetry of lesions. Typical variants are shown in images obtained with duplex
      angioscanning. The authors conclude that there are no principal differences in
      the course of lower limb arteriosclerosis obliterans between diabetics and non
      diabetics. Nevertheless some special features were mentioned, particularly in
      clinical manifestation of intermittent claudication that can be attributed to
      concurrent diabetic neuropathy. Difficulties in clinical interpretation of lower
      limb arterial insufficiency for patients with diabetes mellitus determine the
      necessity of obligatory examination of peripheral vasculature. The authors
      advocate the discrete subclinical stage of the disease with increased rate of
      vascular accidents. The data may be interesting for angiologists, vascular
      surgeons, endocrine legists and other medical professions.

PMID- 12811389
TI  - [The follow up of patients with extracranial pathology of the carotid arteries
      and ischemic disorders of cerebral circulation].
AB  - According to the populational studies, about 50% of ischemic disorders of
      cerebral circulation, both persistent and transient, are induced by thrombotic or
      embolic complications of atherosclerotic plaques which produce an adverse effect
      on the large and small caliber arteries; about 20-25% is associated with lesion
      of the small diameter intracranial vessels, about 20% with embolism from the
      heart, and the remaining disorders fall within other rare causes. The prevalence
      of atherosclerotic lesions of the vessels feeding the brain, the severity of
      their clinical manifestations, insufficient efficacy of conservative therapy and
      the high risk of surgical treatment remain as before a matter of great medical
      and social concern. In connection with an appreciable progress of vascular
      surgery carotid endarterectoray (GEAE) as one of the radical approaches to
      correction of the pathology of the carotid artery segment is widespread at the
      large centers of vascular surgery of different countries. However, in spite of
      the fact that CEAE is an advanced and radical technique of preventive operation,
      it produces only a local effect on vascular diseases whereas the other, no less
      important pathogenetic mechanisms leading to disorders of cerebral circulation
      remain unchanged and demand drug correction to avoid repeated disorders of
      cerebral circulation. Analysis of the long-tern results evidences a stable and
      lasting effect of CEAE. The postoperative clinical manifestations can be used as
      the main criterion for the efficacy of CEAE, especially as compared to the purely
      conservative therepy. The results of the long-term follow up (over the period as
      long as 15 years) of a large group of operated patients demonstrate that the
      majority of them did not show the emergence of the new focal neurologic
      symptomatology in the ipsilateral hemisphere and only a small percentage of cases
      developed stroke. The major western statistics provide the analogous results.

PMID- 12811390
TI  - The first experience with endovascular stenting of the iliac veins in patients
      suffering from post-thrombophlebitic disease.
AB  - This paper describes the results of the first experience with endovascular
      stenting of the iliac veins in patients suffering from post-thrombophlebitic
      disease. During 11 months, the patient with a history of segmental venous
      thrombosis and involvement of the left iliac veins received conservative
      treatment which included phlebotropic therapy and elastic compression. Despite
      these measures the patient demonstrated the symptoms of venous insufficiency such
      as edema, and pains in the left lower extremity. In addition, control
      ultrasonography and radionuclide examinations revealed chronic occlusion of the
      left iliac veins. In view of this circumstance we performed endovascular
      dilatation and stenting of the iliac veins. The postoperative period was
      uneventful. After two months the pains in the left lower extremity and its edema
      were fully removed. Control radionuclide phleboscintigraphy demonstrated complete
      patency of the left iliac veins. So, endovascular stenting is an effective and
      safe modality for the treatment of the occlusive forms of post-thrombophlebitic
      disease.

PMID- 12811391
TI  - Duplex scanning potential at reconstruction of main veins.
AB  - The purpose of the present study was to determine the duplex scanning (BS)
      potential for the evaluation of the results of reconstructive operations for
      postthrombotic disease. We examined 89 patients who underwent different
      reconstructions on the deep veins of the lower extremities. The operations
      included crossover vein graft in unilateral occlusions of the iliac veins (36
      patients), bypass grafting in occlusion of the femoral and popliteal veins (12),
      transposition (23) and autotransplantation (18) of the venous segments containing
      good valves in recapitalization of the deep great veins. Ultrasound diagnosis of
      the patency of the veno-venous grafts and function of the transposed or
      transplanted valves had an accuracy of 100%. DS has been demonstrated to compare
      very favourably with contrast phlebography. We present the functional
      characteristics of the blood flow in the veno-venous bypasses when the patient is
      in the horizontal and vertical positions at rest and under conditions of
      hydrodynamic provocation of the retrograde blood flow at Valsalva's test,
      compression tests and of the antegrade blood flow at physical exercise. The tests
      which upgrade the effectiveness of ultrasonography have been worked out. The
      morphological variants of lesion of the transplanted venous valve cusps have been
      established. It is demonstrated that the main cause of valvular incompetence of
      autotransplants lies in supravalvular (sinusoidal) thrombosis which develops in
      the early postoperative time, thereby giving rise to the block of the cusps of a
      transplanted valve. The data on the hemodynamics of venous autotransplants,
      obtained in the course of the study enable one to select an optimal variant of
      reconstructive operation, to delineate the postoperative treatment policy and to
      predict the results of surgical intervention.

PMID- 12811392
TI  - [Noninvasive diagnosis of the main forms of venous hypertension in patients with
      varicosity].
AB  - The mechanisms of the development of venous hypertension were studied in 212
      patients with varicosity. The clinical and instrumental research methods
      (rheovasography, photoplethysmography, duplex scanning) were employed. Two groups
      of patients suffering from superficial (simple) and deep (complicated) forms of
      venous hypertension were distinguished. The superficial form (85.3%) largely
      occurs under the action of the hydrostatic force of gravitation nature. The axial
      reflux via the sapheno-femoral and sapheno-popliteal anastomoses, which occurs
      when the patient is in the vertical position produces insufficiency of the
      superficial venous valves. The musculovenous pump maintains its function. That is
      why the hydrody-namic effects via the insufficient perforating veins play a less
      important part in the development of venous stasis. Trophic disorders emerge 20
      30 years after the disease onset and are associated with the development of
      fairly intensive blood refluxes in the superficial and perforating veins.
      Dysfunction of the musculovenous pump of the lower extremities underlies the
      formation of deep hypertension (14.7%). Primary valvular insufficiency of the
      deep veins induces the formation of hemo-dynamically significant refluxes in the
      deep, superficial and perforating veins. The work of the musculovenous pump is
      far from promoting venous return. On the contrary, the movement is associated
      with an increase in blood volume in all elements of the pump. At first this leads
      to phlebostasis and then to capillary stasis, provoking the development of
      trophic disorders at the early stages of disease.

PMID- 12811393
TI  - [Lower limb chronic venous insufficiency: contemporary problems in diagnosis,
      classification and treatment].
AB  - The paper presents a brief analysis of contemporary problems in management of
      patients with lower limb chronic venous insufficiency (CVI). During the last
      decade occurrence of complicated CVI tended to diminish resulting from well
      directed efforts in improvement of diagnostic and therapeutic methods, active
      participation of different specialists in management programs. The paper
      addresses the questions of assessment planning dependent on CVI manifestation and
      role of various diagnostic modalities (morphological and functional). The scope
      of therapeutic methods is enumerated, with special attention to their practical
      value and unresolved issues. Ultrasonography enabled to broaden indications for
      minimally invasive procedures in varices surgery. Accumulation of rich experience
      in sclerotherapy made possible to develop distinct indications for the procedure.
      The authors delineate promising directions for further research in CVI
      management.

PMID- 12811394
TI  - [The problem of postoperative venous thromboembolic complications in general
      surgery].
AB  - The paper reviews occurrence, diagnostic tools venous thromboembolic
      complications. Cost effectiveness of preventive measures for venous thrombosis
      and pulmonary embolism in general surgery is analysed. The study included 45
      patients who underwent elective (21) and urgent (24) abdominal and pelvic
      interventions. Each patient was examined with ultrasonic with color Doppler
      imaging before and 8-10 days after surgery. Deep venous thrombosis of lower limbs
      was diagnosed in 11.1%, most of cases being asymptomatic. Ultrasonic
      angioscanning appeared to be an acute and reliable diagnostic tool for this
      pathology. Various approaches to the management of patients at thrombotic risk
      are reviewed. Cost effectiveness analysis of anticoagulation prevention for
      postoperative venous thromboembolic complications must address the problem: is
      prevention outcome worth those extra efforts? Surveillance of 500 patients at
      high thrombotic risk has shown that preventive use of low weight heparin
      (Clexane) is economically beneficial then conventional Heparin, the more in the
      absence of special preventive strategy. Targeted prevention in patients with
      different risk of postoperative venous thromboembolic complications can yield
      more then 3-fold reduction in occurrence of these complications.

PMID- 12811395
TI  - [Clinical assessment of phlebopathy severity by specification of leg heaviness
      symptom].
AB  - The paper presents the first attempt to differentiate phlebopathy severity on the
      basis of subjective information, which serves a key parameter of decompensation
      assessment reflecting individual range of daily living activity and functional
      load. Phlebopathy is defined as structural and functional insufficiency of venous
      wall, decreased ability to maintain stable volume both of particular veins and
      leg venous system as a whole during prolonged orthostasis. From 1995 to 2001
      different forms of leg varices were diagnosed and treated in 583 patients. The
      most common complaint expressed by 567 patients (97.0%) was the heaviness and
      bursting pain in legs caused by daily orthostasis. Four clinical groups were
      clearly defined: 0 grade - no heaviness in legs; 1 grade - episodes of heaviness
      after excess daily load; 2 grade - regular heaviness in legs not demanding
      obligate evening rest with updrawn legs; 3 grade - permanent heaviness in legs
      demanding rest with legs updrawn. Permanent symptom (the last 2 groups) can be
      subdivided according to timing of symptom onset: a) in the afternoon, b) in the
      forenoon. The data analysis demonstrated that the symptom of leg heaviness during
      orthostasis caused by increased creep of venous walls was be a subjective
      equivalent to phlebopathy severity. The time of symptom onset and degree of
      manifestation correlated with the severity of venous wall incompetence. This
      method can be used to evaluate functional status of leg venous circulation both
      during initial assessment and for treatment or rehabilitation monitoring.

PMID- 12811396
TI  - [The impact of cardiac status and arterial hypertension on the results of
      surgical treatment of patients over 70 years with abdominal aortic aneurysms].
AB  - The recent decades were marked by a noticeable growth of the number of patients
      over 70 years with abdominal aortic aneurysms (AAA). As a rule, in view of the
      high incidence of coexistent cardial pathology and arterial hypertension in
      patients of this age group with AAA, the risk of the forthcoming operation may be
      fairly high. The aim of the work was to study the effect of the initial cardial
      status of the patients and lesion of the target organs in arterial hypertension
      on the results of surgical treatment of patients over 70 years with abdominal
      aortic aneurysms. The study accrued 50 patients with atherosclerotic aneurysms of
      the abdominal aorta who underwent operation on a scheduled basis over the period
      1990-2000. The patients age varied from 70 to 85 years. The mean age was 73.2
      /+2.9 years. The aneurysmal diameter varied from 4 to 12 cm (mean 6.9-/+2.09 cm).
      Aneurysms up to 5 cm in diameter were present in 15 (25.4%) patients, those up to
      7 cm in 23 (40%), and aneurysms exceeding 7 cm were identified in 21 (35.6%)
      patients. 43 (72.9/5%) patients were in the patient group with an asymptomatic
      disease course and 16 (27.1%) patients were in a group with symptomatic AAA,
      Coexistent CAD was discovered in 96.6% and arterial hypertension in 62.5% of
      patients. The mean incidence of coexistent CAD and arterial hypertension
      constituted 1.64-/+0.3. The initial cardial status of the patients was evaluated
      according to the point classification proposed by Rutherford. Lesion of the
      target organs was evaluated according to the WHO classification (1996). Analysis
      of the results obtained has demonstrated that despite the presence of CAD in the
      majority of patients over 70 years with AAA, its severity was equal to 0-2 points
      and the mean point of postoperative cardial events in these patients turned out
      minimal (within the range of one point). In the presence of arterial hypertension
      and lesion of the heart as a target organ, the risk of cardial complications was
      1,5-2 times as increased depending on the severity of initial cardial pathology.

PMID- 12811397
TI  - Small abdominal aortic aneurysms.

PMID- 12811398
TI  - [Ruptures of abdominal aortic aneurysms. The clinical course and classification].
AB  - Surgical treatment of abdominal aortic aneurysm (AAA) ruptures is a matter of
      great concern in current vascular surgery. The results of surgical treatment of
      patients presenting with such severe disease could have been improved due to the
      early and correct diagnosis. The present work is concerned with a study into the
      characteristic features and causes of the atypical clinical manifestations and
      the course of AAA ruptures as well as with the development of the classification
      accessible for practical uses. Later on it would allow to refine the treatment
      policy for an extremely severe patient group and to define a permissible
      algorithm of examination in the postoperative time and would favour the early
      diagnosis of disease. The study is based on an analysis of the clinical course of
      AAA rupture in 53 patients operated on at the Department of Vascular Surgery.
      MONIKI. The clinical manifestations were typical in 46 (86.8%) patients. The
      progressing course of AAA rupture was observed in 21 (39.6%) patients; the
      disease ran a wave-like course in 17 (32.1%) patients. Stabilization of the
      condition was marked in 15 (28.3%) cases. In 39 (73.6%) cases, AAA rupture
      affected the retro-peritoneal space, the free abdominal cavity was affected in 8
      (15.1%), the duodenum in 2 (3.8%), the sigmoid intestine in 2 (3.8%), and the
      inferior vena cava in 2 (3.8%) of cases. The rupture of the posterior wall of the
      aortic aneurysm was identified in 29 (54.7%), of the lateral wall in 12 (22.6%),
      and of the anterior wall in 8 (15.1%) patients. Four (7.5%) patients demonstrated
      aneurysmal rupture of the iliac artery. The clinical manifestations of AAA
      rupture were marked by polymorphism whereas its course was often masked by other
      diseases making it difficult to establish the early and correct diagnosis. The
      difficulties in the diagnosis of AAA ruptures gave rise to a lot of diagnostic
      errors and late hospitalization to specialized unita.

PMID- 12811399
TI  - Surgical treatment of patients with renovascular hypertension secondary to
      aneurysmal lesions of the renal arteries.
AB  - The paper analyzes the results of examination and surgical treatment of 71
      patients with renal artery (RA) aneurysms which constituted 3% among all the
      subjects treated and examined at the Russian Scientific Centre of Surgery,
      Russian Academy of Medical Sciences (RSCS RAMS). Fibromuscular dysplasia caused
      RA aneurysm most frequently (60%). Contrast radioangiography was the basic
      modality used in the diagnosis of RA aneurysms. While making decision as to
      whether the surgical treatment is feasible, preference was given to
      reconstructions on the renal arteries in order to reduce systemic arterial
      pressure and to maintain renal function. Resection of the aneurysmal renal artery
      was resorted to most frequently, followed by establishment of an end-to-end
      anastomosis (38.2%). Lateral resection of RA aneurysm was employed only in the
      event of its eccentric bulging and when its diameter did not exceed 15-20 mm
      (22.1 %). There were no lethal outcomes. The positive results could be obtained
      in 93.6% of patients. In the long-term postoperative period, the stable positive
      results were recorded in 60.9% of patients with a history of reconstructions on
      the renal arteries for their aneurysmal lesion.

PMID- 12811400
TI  - Results of primary reconstructions in patients with lesion of the tibial
      arteries.
AB  - An analysis was made of 146 primary reconstructions performed in 141 patients
      with occlusion of the arteries of the femoropopliteal segment and leg. At the
      hospital stage an improvement of the clinical status was attained after primary
      operations in 98% of cases. The five-year cumulative bypass patency after
      operations.accounted for 43.5% while the limbs could be saved in 91.5% of cases.
      The results obtained in patients with stage 2B chronic arterial ischemia
      (according to the A.V.Pokrovsky classification, 1979) coincided with the results
      of bypass grafts of the popliteal artery (the 5-year patency was 56.9% with the
      limbs saved in - 81.2% of cases), whereas the results of in situ vein bypass were
      marked by a significantly better cumulative patency in the long-term period.

PMID- 12811401
TI  - [The long-term results of surgical treatment of critical lower limb ischemia by
      autotransplantation using different tissues].
AB  - Presented herein is an analysis of the 15-year results of surgical treatment of
      critical lower limb ischemia (stage IV chronic ischemia according to Fontaine -
      Pokrovsky classification) in patients suffering from chronic occlusive diseases
      of lower lirtb arteries (CODLLA) with subtotal and total obliteration of the
      peripheral arterial system. In total lesion of the talotibial segment when the
      patients could not be rendered assistance using conventional vascular surgery or
      when roentgenoendovascular deobliterution was not feasible, use was made of
      indirect revascularizntion of the ischemized limb by autotransplantation of soft
      tissue complexes. A flap of the broadest muscle of back (FBMB) was employed as an
      autotransplant in 56 patients, the greater omentum in 12 patients, and a flap of
      the anterior dentate muscle (FADM) was used in 9 patients. Twenty-five patients
      with diffuse lesion of the popliteal talotibial segment were provided combined
      limb revascularization, when the feasibility of standard bypass graft appeared
      fairly questionable. The majority of patients were placed under annual
      observation. It is noteworthy that the monitoring of the ankle/brachial index
      (ABI), oxygen tension on the foot (TcpO2) and of the proximal-distal temperature
      gradient as well as the assessment of the number of saved limbs and of the
      patients' quality of life allow to regard the technique as highly effective in
      the strategy of the salvage of the terminally inchemized limb from amputation.
      The technique also makes it possible to solve the problem of patch plasty of the
      trophically and necrotically changed foot and to maintain its support capacity.
      Combined revascularization makes it possible to unite the effect of direct and
      indirect reconstruction of the arterial system and to perform bypass graft in non
      conventional situations.

PMID- 12811402
TI  - The clinical diagnosis of cranial nerve injuries at operations on the carotid
      arteries.
AB  - Operation on the carotid arteries (CA) prevent strokes in patients with
      occlusions and stenoses of these arteries. We have worked out the measures for
      preventing perioperative strokes. During interventions on the CA, iatrogenic
      injuries to the cranial nerves (CN) are paid little attention. 1186 patients
      underwent 1362 operations. There were 26 lethal outcomes and 38 strokes. 146
      (0.7%) cases of CN injuries were documented. Of these, there were 2 (0.1%)
      injuries to the accessory nerve, 14 (1%) to the glossopharyngeal nerve, 28 (2%)
      to the hypoglossal nerve, 46 (3.4%) injuries to vagal nerve branches, and 56
      (4.2%) to facial nerve branches. In 42 patients, neuropathies acquired the
      'permanent' character. We describe the symptomatology of injuries to different CN
      pairs consequent on carotid operations and the algorithm of their diagnosis. CN
      injuries deteriorate the results of operations and decrease quality of life of
      the patients. Early diagnosis and correction of the sequelae of iatrogenic
      injuries to the CN is a reserve for the refinement of the results of operations
      on the CA.

PMID- 12811403
TI  - [Stenting of left common carotid artery kinking in the region of carotid
      subclavian anastomosis in a patient operated for occlusion of left subclavian
      artery].
AB  - The paper presents a case report of left common carotid artery kinking treated by
      stenting in a patient with aortoarteritis. The kink had developed 10 months after
      performance of carotid-subclavian anastomosis for occlusion of left subclavian
      artery and steal syndrome. The stenting procedure of left common carotid artery
      is described. Follow-up for 42 months and control angiography 6 months after
      stent implantation demonstrated good outcome and regression of neurological
      symptoms. Special features of stenting procedure in coiled artery with unaltered
      walls are analysed. The authors mention that carotid stenting in this patient was
      the most appropriate method of surgical treatment. It is the first description of
      stent use for carotid artery kinking correction.

PMID- 12811404
TI  - [Dislocation of the closing element of the disk mechanical graft at aortic valve
      replacement].
AB  - Presented herein is the first case of dislocation of the closing element of the
      artificial low-profile aortic valve to the abdominal aorta, which happened during
      replacement. Toward completion of extracorporeal circulation a 37-year-old man
      showed the signs of aortic insufficiency because of dislocation of the closing
      element. After resumption of extracorporeal circulation repeated replacement was
      accomplished. To detect the site of graft cusp embolism, transesophageal
      echocardiography and duplex scanning of the abdominal aorta were employed. On the
      18th day following the first intervention the patient developed thromboembolism
      to the distal arterial bed. Emergency thrombectomy from the arteries of the right
      lower extremity was performed and a foreign body was removed from the abdominal
      aorta, using left-sided thoracophrenolumbotomy. The patient was discharged from
      the clinic in a satisfactory condition.

PMID- 12811405
TI  - [Treatment and rehabilitation strategy for patients with lower extremity stump
      ischemia].
AB  - The paper is concerned with evidence for the choice of the treatment and
      rehabilitation policy of patients suffering from lower extremity stump ischemia.
      Altogether 446 patients with obliterating diseases of arteries and unilateral
      post-amputation defects of the lower extremities were examined. Of these, degree
      III-IV stump ischemia was verified in 90 patients, transient stump ischemia was
      present in 259 patients. In 30 patients, stump pains or defects of the skin were
      determined by defects and discuses of the stump; 67 patients were identified to
      have no clinical signs of ischemia and no defects or diseases of the stump, 43
      patients underwent arterial reconstructions whereas reamputations of the
      extremity were undertaken in 29 patients. The remaining patients with stump
      ischemia received conservative therapy. The algorithm of the choice of the
      treatment policy and rehabilitation of patients was worked out depending on the
      severity of the clinical manifestations of stump ischemia and the level of post
      amputation defect.

PMID- 12811406
TI  - British Cancer Research Meeting. Bournemouth, United Kingdom, 2-5 July 2003.
      Abstracts.

PMID- 12811412
TI  - Interactive effect of the glutathione S-transferase genes and cigarette smoking
      on occurrence and severity of coronary artery risk.
AB  - Cardiovascular diseases and cancer are the main causes of death in developed
      countries. Mortality trends for these diseases suggest that they share common
      pathogenetic mechanisms. Glutathione S-transferase (GST) is a family of enzymes
      that detoxify reactive electrophiles, particularly present in tobacco smoke.
      Glutathione S-transferase null M1 and T1 (GSTM1 and GSTT1) genotypes have often
      been associated with increased risk of developing cancer. Our hypothesis was that
      the polymorphic GSTM1 and GSTT1 genes modulate the risk of smoking-coronary
      artery disease (CAD). We evaluated the distribution of GST genotypes in 430
      angiographically defined patients (308 CAD and 122 non-CAD). The frequencies of
      GST null genotypes did not differ significantly between patients with CAD and
      without CAD. However, smokers with GSTM1 and GSTT1 null genotypes had a
      significantly higher risk of CAD than never-smokers with these genotypes present
      (OR 2.2 and 3.4 for smokers with null GSTM1 and GSTT1 genes, respectively). There
      was also evidence of multiple interaction between GSTM1 and GSTT1 deleted
      genotypes and smoking. In nonsmokers carrying both null genotypes the risk of CAD
      was 0.66. In smokers with both present genotypes the OR was 1.5 and was
      significantly increased in smokers with concurrent lack for GSTM1 and GSTT1 genes
      (OR=4.0). Moreover, smokers lacking GST genes had both more stenosed vessels and
      a higher Duke score than smokers expressing the genes. We also examined the
      levels of DNA damage in 66 men patients using the micronucleus test, a sensitive
      assay for evaluating chromosome damage. Micronucleus levels were higher in
      smokers with null genes than in smokers with present genes. These observations
      suggest that GST-null genotypes strengthen the effect of smoking on CAD risk by
      modulating the detoxification of genotoxic atherogens.

PMID- 12811413
TI  - Gene therapeutic approaches for medullary thyroid carcinoma treatment.
AB  - Medullary thyroid carcinoma (MTC), a neoplasm of thyroid C-cells, is
      characterized by dominant activating mutations in the RET proto-oncogene.
      Currently therapy is restricted to surgical removal of all neoplastic tissue
      lacking alternative forms of treatment such as chemotherapy or radiotherapy.
      Therefore MTC is a particularly attractive target for gene therapeutic
      approaches. Many promising gene therapy strategies have been used in various
      animal models of MTC, showing enhanced antitumoral efficacy, and these will
      hopefully extend our current standard of care in the future. These approaches can
      tentatively be subdivided into four groups: (a) Inhibition of oncogenic RET
      signaling, (b) suicide gene therapy, (c) immunotherapy, and (d) combination of
      immunotherapy and suicide approaches. To block oncogenic signal transduction
      dominant-negative RET mutants were delivered into tumor cells and found to
      possess strong antineoplastic activity, including tumor growth suppression and
      increased animal survival. Suicide gene therapeutic approaches applied to MTC
      treatment featured either gene transfer of herpes simplex virus thymidine kinase
      with concomitant application of ganciclovir or delivery of nitric oxide synthase
      II. Here antitumor effects were attributed to the occurrence of substantial
      bystander activities. Immunotherapy approaches comprised stimulation of immune
      response by delivery of interleukin 2 or 12. Finally, treatment with herpes
      simplex virus thymidine kinase/ganciclovir in combination with interleukin 2 was
      found to be superior over either treatment alone. This review discusses the
      various gene therapeutic approaches applied to MTC treatment in detail, gives an
      overview on the diverse vector systems used to achieve efficient transduction of
      thyroid cancer cells, and points out the strategies employed to accomplish target
      cell selective gene expression thereby contributing to enhanced safety of gene
      therapy for MTC

PMID- 12811414
TI  - [Structured treatment and teaching programs and an improvement in private health
      care lead to a better quality of diabetes care. JEVIN, a population-based trial
      1989/90 up to 1999/2000].
AB  - AIMS AND HYPOTHESES: JEVIN ( Jena's St. Vincent Trial) is a prospective, 10-year
      follow-up, population-based survey of all insulin-treated patients with type 1
      and type 2 diabetes mellitus aged 16-60 years and living in the city of Jena
      (100,000 inhabitants), Thuringia. It aims to show the effects of recent changes
      in the health care system and new treatment strategies. During the period from
      1989/90 to 1994/95, the health care system was decentralized. There has been an
      broad implementation of postgraduate educational courses for primary care
      physicians, of structured treatment and teaching programs (TTP), of intensified
      insulin therapy, and blood glucose self-monitoring for all patients. PATIENTS AND
      METHODS: 190 patients (83% of the target population), 244 patients (90%) and 261
      patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively.
      RESULTS: Up to 1994/95, the relative HbA(1c) (HbA(1c)/mean normal) of patients
      with type 1 diabetes increased (1994/95: 1.65 +/- 0.35 vs. 1989/90: 1.52 +/-
      0.31; p = 0.002). For patients with type 2 diabetes mellitus it remained constant
      (1.75 +/- 0.4 vs. 1.78 +/- 0.31; p = 0.669). During the period from 1994/95 to
      1999/2000, there was a substantial improvement in the relative HbA(1c) of both,
      patients with type 1 (1.48 +/- 0.3; p < 0.0001), and type 2 diabetes (1.47 +/-
      0.25; p < 0.0001). Up to 1999/2000, 87.7% of the patients with type 1 (1989/90:
      0%, 1994/95: 73.2%) and 96.6% of the patients with type 2 diabetes (1989/90: 0%,
      1994/95: 89.7%) participated in TTPs. Similarly, the percentage of patients with
      intensified insulin therapy (type 1/2: 1989/90: 5.3%/3.4%, 1994/95: 80.3%/30.8%,
      1999/2000: 94.7%/48.3%) and the frequency of weekly blood glucose self-monitoring
      (type 1/2: 1989/90: 1 [0-28]/0 [0-21], 1994/95: 25 [0-49]/14 [0-35], 1999/2000:
      28 [0-70]/21 [0-46]) increased. Moreover, there was a drastic improvement in
      private health care: up to 1999/2000, about 90% of all the patients studied were
      treated by primary care physicians who took part in postgraduate educational
      courses. CONCLUSIONS: During the past decade, there has been a substantial
      improvement in the quality of diabetes control. The broad implementation of
      structured TTPs, intensified insulin therapy, and blood glucose self-monitoring
      for patients with type 1 and 2 diabetes mellitus seem to be the major
      cornerstones for the improved quality of diabetes care. However, the impressive
      improvement in the quality of diabetes care in patients with type 2 diabetes
      mellitus seems not to be related mainly to an increase (about 10% vs. 20% in type
      1 diabetes) in the number of patients under specialist care, but rather to an
      improvement in the quality of diabetes therapy administered by private health
      care physicians.

PMID- 12811415
TI  - [Value of endosonography in diagnostic staging of primary gastric lymphoma (MALT
      type)].
AB  - BACKGROUND AND AIMS: The incidence of gastric MALT (mucosa-associated lymphoid
      tissue) lymphomas has significantly increased during the past few years.
      Especially when MALT lymphomas are treated conventionally, e.g., with eradication
      or chemotherapy, an exact classification of the lymphoma is required. The goal of
      this study was to compare the accuracy of endoscopic ultrasound (EUS) with other
      imaging techniques used in the staging of MALT lymphomas. PATIENTS AND METHODS:
      In the setting of a prospective trial with a conservative therapeutic approach
      (Munster Study for GIT-NHL), altogether 44 patients diagnosed with a low-grade or
      high-grade malignant non-Hodgkin's lymphoma (NHL) were included in the study and
      classified according to their relative tumor stage using special diagnostic
      measures, which comprised gastroscopy (esophagogastroduodenoscopy), abdominal
      ultrasound, computed tomography (CT), and EUS. RESULTS: In 42 out of 44 patients,
      EUS identified the lymphoma (in two cases, final diagnosis was possible only by
      histologic analysis). Concerning the identification of a thickening of the
      stomach wall or a fusion of the layers of the stomach wall, EUS had a
      significantly superior score over conventional ultrasound or CT, respectively (p
      < 0.001). In the detection of pathologic lymph nodes, EUS was again significantly
      superior to ultrasound imaging. CT, however, had a statistically similar
      detection rate (p > 0.05). In four cases, EUS underrated a less advanced tumor
      stage with tumor manifestations outside the stomach (IVE). In one case,
      pathologic lymph nodes could be detected only with thoracic CT. In 70% of the
      cases, EUS imaging resulted in higher-grade tumor ranking. In 57% of cases, EUS
      was the only imaging technique to achieve a classification of the tumor stage at
      all. CONCLUSION: In the diagnosis of gastric NHLs, EUS imaging is superior to
      conventional imaging techniques (ultrasound and CT). Therefore, the use of
      endoscopic ultrasound for staging can be regarded as a prerequisite for the exact
      tumor stage classification required in more recent conventional therapeutic
      approaches.

PMID- 12811416
TI  - [Severe acute respiratory syndrome (SARS)].
AB  - Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily
      in Southern China in November 2002, with variable flu-like symptoms and
      pneumonia, in approx. 5% leading to death from respiratory distress syndrome
      (RDS). The disease was spread over more than 30 states all over the globe by SARS
      virus-infected travelers. WHO and CDC received first information about a new
      syndrome by the end of February 2003, after the first cases outside the Republic
      of China had been observed. A case in Hanoi, Vietnam, led to the first precise
      information about the new disease entity to WHO, by Dr. Carlo Urbani, a co-worker
      of WHO/Doctors without Borders, who had been called by local colleagues to assist
      in the management of a patient with an unknown severe disease by the end of
      February 2003. Dr. Urbani died from SARS, as did many other health care workers.
      In the meantime, more than 7,000 cases have been observed worldwide,
      predominantly in China and Hong Kong, but also in Taiwan, Canada, Singapore, and
      the USA, and many other countries, and more than 600 of these patients died from
      RDS. Since the beginning of March 2003, when WHO and CDC started their
      activities, in close collaboration with a group of international experts,
      including the Bernhard-Nocht-Institute in Hamburg and the Department of Virology
      in Frankfurt/Main, a previously impossible success in the disclosure of the
      disease was achieved. Within only 8 weeks of research it was possible to describe
      the infectious agent, a genetically modified coronavirus, including the genetic
      sequence, to establish specific diagnostic PCR methods and to find possible
      mechanisms for promising therapeutic approaches. In addition, intensifying
      classical quarantine and hospital hygiene measures, it was possible to limit SARS
      in many countries to sporadic cases, and to reduce the disease in countries such
      as Canada and Vietnam. This review article summarizes important information about
      many issues of SARS (May 15th, 2003).

PMID- 12811417
TI  - [Update cardiology 2001/2002-part II. From unstable coronary syndrome to terminal
      heart failure].
AB  - The cardiovascular continuum describes the way from risk factors to
      atherosclerosis, acute cardiovascular events (unstable angina and myocardial
      infarction), and development of terminal heart failure and its complications.
      Following this way, advances are reported in the therapy of acute coronary
      syndrome, heart failure, ventricular and supraventricular tachyarrhythmias, and
      stroke in patients with patent foramen ovale. The following issues are reported
      in detail: (1) significance of statins and statin withdrawal, glycoprotein
      IIb/IIIa receptor blocker, acute coronary interventions, aspirin and clopidogrel
      in unstable coronary syndromes, (2) pathogenesis of acute pulmonary edema
      associated with hypertension, (3) cardiac regeneration capability after
      transplantation and myocardial infarction, (4) beta-blocker therapy, efficacy of
      additional angiotensin receptor blocker therapy and multisite biventricular
      pacing in symptomatic (advanced) heart failure, (5) prognosis after ablation of
      the atrioventricular node in patients with atrial fibrillation, (6) primary
      prevention with an implantable defibrillator and resumption of driving after
      implantation, and (7) therapeutic options after cryptogenic stroke and patent
      foramen ovale.

PMID- 12811418
TI  - [HbH disease--a rare differential diagnosis in a patient with anemia and
      abdominal pain].
AB  - CASE REPORT: A 45-year-old Vietnamese male was admitted to hospital with severe
      hypochromic anemia and acute abdominal pain. The peripheral blood smear showed
      extreme anisocytosis and poikilocytosis as well as teardrops and target cells.
      Hemoglobin electrophoresis and brilliant cresyl blue staining revealed hemoglobin
      H (HbH) disease with an infection-associated hemolytic crisis. CONCLUSION: In the
      diagnostic workup of hemolytic and hypochromic anemia, HbH disease as a special
      type of alpha-thalassemia should be considered early. In patients from Eastern
      Asia with a mean corpuscular hemoglobin (MCH) < 25 pg, hemoglobin analysis should
      be performed in order to avoid unnecessary diagnostic procedures. The prognosis
      of HbH disease is generally favorable, and symptomatic treatment is only
      recommended during hemolytic crises in association with, e.g., infections or
      pregnancy.

PMID- 12811419
TI  - [Massive bleeding symptoms in two patients with factor V inhibitor and
      antiphospholipid antibodies after treatment with ciprofloxacin].
AB  - BACKGROUND: The development of factor V inhibitor is very rare, especially in
      combination with antiphospholipid antibodies. CASE REPORT: The paper describes
      the course of two patients with factor V inhibitor, antiphospholipid antibodies
      and massive bleeding symptoms after treatment with ciprofloxacin. At that time,
      ciprofloxacin was the only new drug given. DIAGNOSIS AND CLINICAL COURSE: First
      changes of the coagulation system were detected 4 days after start of treatment.
      In one case, occurrence was transient, and normalization was observed after
      terminating ciprofloxacin treatment. The other case ended with massive muscular
      and visceral bleedings and cardiovascular failure. Factor V inhibitor and
      antiphospholipid antibodies could be demonstrated even after termination of
      ciprofloxacin therapy. CONCLUSION: The association of treatment with
      ciprofloxacin and development of factor V inhibitor and antiphospholipid
      antibodies is probably diagnosed to rarely. These two cases emphasize the
      necessity of meticulous clarification of a prolonged activated partial
      thromboplastin time (aPTT) and a drop in prothrombin time (PT) during and after
      ciprofloxacin treatment.

PMID- 12811420
TI  - Image fusion analysis of 99m Tc-HYNIC-octreotide scintigraphy and CT/MRI in
      patients with thyroid-associated orbitopathy: the importance of the lacrimal
      gland.
AB  - The aim of this study was to describe the anatomical structures that show uptake
      of the somatostatin analogue octreotide in patients with thyroid-associated
      orbitopathy (TAO). The study population comprised a series of 20 TAO patients
      attending the out-patient thyroid clinic and 12 patients presenting head or neck
      tumours. Scintigraphy was carried out with our newly developed tracer, technetium
      99m labelled EDDA-HYNIC-TOC ((99m)Tc-TOC). Morphological imaging was done with
      either magnetic resonance imaging or X-ray computed tomography without contrast
      medium. Both imaging procedures were done within an interval of 3-4 weeks. For
      the image fusion procedure, specific external reference markers were used for
      each imaging modality. The markers were screwed onto a reference frame, which was
      held in place via a vacuum-fixed mouthpiece. The anatomical structure showing
      tracer uptake that was most frequently recognised was the lacrimal gland,
      followed by the retronasal area, cervical lymph structures, salivary glands, the
      anterior insertion points of the extra-ocular muscles and discrete areas of the
      neck extensor muscles. The lacrimal gland and the retronasal area showed the
      highest and most frequent uptake of (99m)Tc-TOC in TAO patients, whereas such
      uptake did not occur in the retrobulbar space. In spite of knowledge of these
      results of image fusion, no changes in the involved structures could be detected
      on morphological imaging. It is concluded that binding of (99m)Tc-TOC is more
      frequently localised to the anterior compartment of the eye and to the neck. The
      previously used term "orbital" uptake should be abandoned and replaced by a
      descriptive term relating to the anatomically recognised structure showing tracer
      accumulation, i.e. the lacrimal gland. The uptake of octreotide by lymphoid and
      salivary glands opens a new field of investigation related to the physiology of
      somatostatin.

PMID- 12811422
TI  - [(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine
      transporter in monkey and human brain.
AB  - The aim of this study was to explore the potential of a new selective dopamine
      transporter (DAT) compound as a radioligand for positron emission tomography
      (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3
      iodoprop-2 E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) was
      radiolabelled by the O-methylation approach and the binding was characterised by
      PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were
      measured by gradient high-performance liquid chromatography. O-methylation of the
      corresponding free acid precursor with [(11)C]methyl triflate gave high
      radiochemical yield (80%) and specific radioactivity (55 GBq/ microM).
      [(11)C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum
      than in the cerebellum at peak equilibrium, which appeared 55-65 min after
      injection. Displacement and pretreatment measurements using unlabelled beta-CIT,
      GBR 12909, cocaine, citalopram and maprotiline confirmed that [(11)C]PE2I binds
      selectively to DAT. In a preliminary study in one human subject the radioactivity
      ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8,
      respectively, at peak equilibrium, which appeared at 40-50 min and 20 min,
      respectively, after injection. The fraction of the total radioactivity in monkey
      and human plasma representing unchanged [(11)C]PE2I was 15-20% at 40 min after
      injection. The present characterisation of binding in monkey and man suggests
      that [(11)C]PE2I is a suitable PET radioligand for quantitative regional
      examination of DAT in man.

PMID- 12811421
TI  - The role of SPET and PET in monitoring tumour response to therapy.
AB  - Positron emission tomography (PET) and single-photon emission tomography (SPET)
      are cross-sectional, quantitative functional imaging modalities in routine use in
      oncology for the initial staging of cancer, the assessment of patients with
      recurrent or residual disease and, more recently, for monitoring tumour response
      to therapy. Both PET and SPET can track tumour biological and metabolic changes
      caused by therapy or by disease progression, which usually precede the anatomical
      alterations conventionally detected by anatomical imaging methods. These highly
      sensitive functional imaging modalities have been used for the early assessment
      of subclinical tumour response, the evaluation of therapy after its completion
      and the detection of viable recurrent or relapsing tumour. Timely assessment of
      response to treatment using PET and SPET may result in modifications in treatment
      planning and individualisation of therapy and may have prognostic value for the
      long-term outcome. This review attempts to summarise the current data available
      on the expanding role of SPET and PET, using a variety of tracers, in monitoring
      tumour response to therapy in a wide range of malignancies, with emphasis on
      their clinical impact.

PMID- 12811424
TI  - MR imaging of lipoma arborescens and the associated lesions.
AB  - OBJECTIVE: To describe the typical features of lipoma arborescens on MR imaging
      with pathologic correlation and to evaluate the associated lesions within the
      joints. DESIGN AND PATIENTS: The MR imaging findings of 32 patients with the
      diagnosis of lipoma arborescens of the knee (n=32) and shoulder (n=1) were
      reviewed. The diagnosis of lipoma arborescens was confirmed by the histologic
      findings in 12 cases and the other 21 cases were diagnosed by the characteristic
      MR imaging features. One patient had bilateral lipoma arborescens of the knee
      joint. RESULTS: MR imaging showed a typical pattern of villous lipomatous
      proliferation of the synovium in all cases, as a diffuse pattern in 79% (26/33)
      of cases and as a dominant mass-like lesion in 21% (7/33) of cases. The
      associated MR pathology in the knee was (n=32): joint effusion (100%),
      degenerative changes (87%), meniscal tear (72%), synovial cysts (38%), bone
      erosions (25%), chondromatosis (13%), patellar subluxation (6%) and discoid
      meniscus (3%). In all cases except two there was associated pathology of the
      knee. MR imaging showed an associated rotator cuff tear in the lipoma arborescens
      of the shoulder. CONCLUSION: The characteristic MR features of lipoma arborescens
      allows an accurate diagnosis of this rare lesion, which is almost always
      associated with other chronic pathology of the joint in the elderly.

PMID- 12811423
TI  - Dosimetry in leakage of (188)Re-DTPA during intracoronary balloon brachytherapy.
AB  - Rhenium-188 is reported to be one of the best radionuclides for intracoronary
      balloon brachytherapy. Among several preparations of (188)Re available for
      brachytherapy, (188)Re-diethylene triamine penta-acetic acid (DTPA) and (188)Re
      mercaptoacetyltriglycine (MAG3) are recommended owing to their rapid excretion
      via the renal system and the absence of accumulation in the thyroid. The aim of
      this study was to calculate the dose of radiation exposure in a real human
      accident. During a 4-year clinical trial of (188)Re-DTPA balloon brachytherapy in
      242 patients, there was one accident involving balloon leakage. Dosimetry was
      performed by both image-based and biological analysis. The radiation exposure to
      the whole body was calculated as 113 mGy by image-based analysis and 83 or 88 mGy
      by biological analysis, which was approximately half the reported dose in the
      case of (188)Re-perrhenate. The radiation exposures to other vital organs were
      also within the tolerated ranges. We conclude that (188)Re-DTPA has better
      clinical feasibility and safety for intracoronary balloon brachytherapy than
      (188)Re-perrhenate.

PMID- 12811425
TI  - Reductive dehalogenation of tetrachloroethylene by microorganisms: current
      knowledge and application strategies.
AB  - Reductive anaerobic dehalogenation is a useful method for remediation of sites
      contaminated by chlorinated ethylenes, where hydrogen concentration plays the key
      role. Under anaerobic conditions, dehalogenating bacteria compete best against
      methanogenic consortia when the hydrogen level is low; and methanogenic consortia
      outplay dehalogenating bacteria when the hydrogen level is high. Thus, in an
      anaerobic mixed culture, efficient use of hydrogen for dehalogenation can be
      achieved by strategies that maintain hydrogen at a certain low concentration.
      However, due to the role of acetate, expected dehalogenating results cannot be
      obtained and unexpected methane formation can be encountered in practice.

PMID- 12811426
TI  - Contribution of hydrolytic enzymes produced by saprophytic fungi to the decrease
      in plant toxicity caused by water-soluble substances in olive mill dry residue.
AB  - We studied the influence of saprophytic fungi on the toxic effect that the water
      soluble substances in dry residues from olive (ADOR) have on the growth of
      plants. All saprophytic fungi were able to decrease the phytotoxicity of ADOR,
      although the toxicity of this residue did not decrease in the same way.
      Penicillium chrysogenum was able to reduce the toxicity of ADOR when this residue
      was applied at the highest dose of 15%. Fusarium lateritum, F. graminearum and
      Mucor racemosus were able to reduce the toxicity of ADOR when this residue was
      applied at the intermediate doses. However, F. oxysporum decreased the
      phytotoxicity of ADOR only when the residue was applied at the lowest dose of
      2.5%. All saprophytic fungi tested produce endoglucanase,
      endopolymetylgalacturonase and endoxiloglucanase when grown in the presence of
      ADOR. A close relationship was found between the decrease in the phytotoxicity of
      ADOR and the amount of hydrolytic enzymes produced by the saprophytic fungi.
      These results shows that hydrolytic enzymes can be important in the degradation
      of phytotoxic substances present in olive mill dry residue.

PMID- 12811427
TI  - MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing
      pathogens with single expressed major histocompatibility class I and class II
      loci.
AB  - Few studies have yet addressed the functional aspects of MHC molecules in fish.
      To lay the foundation for this, we evaluated the association between disease
      resistance and MHC class I and class II polymorphism in Atlantic salmon.
      Standardized disease challenge trials were performed on a semi-wild Atlantic
      salmon population with subsequent MHC typing and statistical analysis. The
      pathogens employed were infectious salmon anaemia virus (ISAV) causing infectious
      salmon anaemia and the Aeromonas salmonicida bacteria causing furunculosis. The
      material consisted of 1,182 Atlantic salmon from 33 families challenged with A.
      salmonicida and 1,031 Atlantic salmon from 25 families challenged with ISAV. We
      found highly significant associations between resistance towards infectious
      diseases caused by both pathogens and MH class I and class II polymorphism in
      Atlantic salmon. The observed associations were detected due to independently
      segregating MH class I and class II single loci, and inclusion of a large number
      of fish allowing an extensive statistical analysis.

PMID- 12811428
TI  - Presence and primary sequence of a high-affinity IgG receptor on canine
      mastocytoma (CM-MC) cells.
AB  - Mast cells play a central role in IgE-dependent allergic responses. Although they
      have been reported to express only low-affinity IgG receptors and no high
      affinity receptors (FcgammaRI), our recent study showed that canine mastocytoma
      CM-MC cells are activated by monomeric canine IgG, suggesting the presence of
      FcgammaRI on CM-MC cells. In the present study, we measured the affinity of
      canine IgG with CM-MC cells, determined the presence of the FcgammaRI protein and
      mRNA, and identified the cDNA sequence of it. The results showed that (7.5+/
      3.1)x10(4) receptor molecules are expressed on a CM-MC cell with a Ka of (9.1+/
      1.6)x10(7)M(-1) for binding to monomeric canine IgG. Canine IgG-conjugated beads
      precipitated an approximately 72-kDa surface protein, whose size is consistent
      with that of the FcgammaRI alpha subunit of humans and mouse. The expression of
      FcgammaRI mRNA was detected by reverse transcriptase polymerase chain reaction
      (RT-PCR), and the cDNA encoding the FcgammaRI alpha subunit was found to be 84%
      and 78% similar to that of humans and the mouse, respectively. The predicted
      amino acid sequence was 72% and 63% identical, respectively. Canine mastocytoma
      CM-MC cells are therefore very useful for studying FcgammaRI-mediated signal
      transduction in mast cells.

PMID- 12811429
TI  - Relationship between the tumor necrosis factor alpha polymorphism and the serum C
      reactive protein levels in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the
      gastrointestinal tract, including ulcerative colitis (UC) and Crohn's disease
      (CD). The aim of the study was to determine the prevalence of the tumor necrosis
      factor alpha (TNF-alpha) promoter polymorphisms at positions -238 and -308, and
      to measure the serum CRP levels in CD and UC patients and in a healthy
      population. The TNF-alpha gene polymorphisms were determined by the PCR-RFLP
      method. Samples of 74 CD and 50 UC patients and 138 healthy Hungarian volunteers
      were examined. The G-->A substitution at position -308 (designated the TNF2
      allele) was significantly less frequent among IBD patients than in the control
      group (P=0.0009); 15% of the CD patients and 18% of the UC patients carried the
      mentioned allele, which was significantly less frequent compared with the healthy
      population (33%, P=0.0035 and P=0.036, respectively). No difference in the G-->A
      substitution at position -238 was observed. We found the median CRP levels to be
      significantly higher in the active phase of the disease than in the inactive
      phase among the -308A allele carriers (P=0.002), while this difference was not
      significant when the CRP levels in the active and inactive phases were compared
      among the -308GG homozygous patients (P=0.084). The decreased frequency of the
      TNF2 allele (known to be associated with elevated TNF-alpha production) in IBD
      may determine the severity of IBD through its interaction with plasma CRP levels,
      and may modify the pathogenesis of this chronic inflammatory disease.

PMID- 12811430
TI  - Estimating domain orientation of two human antibody IgG4 chimeras by
      crystallohydrodynamics.
AB  - A modified crystallohydrodynamic approach introduced in 2001 is applied to two
      human IgG4 constructs from mouse IgG1. The constructs were point mutants of the
      chimeric antibody molecule cB72.3(gamma4): cB72.3(gamma4A), devoid of inter-chain
      disulfide bridging, and cB72.3(gamma4P), which has full inter-chain bridging. As
      before, the known crystallographic structures for the Fab and Fc domains were
      combined with the measured translational frictional ratios to obtain an estimate
      for the apparent time-averaged hydration of the domains and hence for that of the
      intact molecule. The original approach was modified with the hydrated dimensions
      of the domains being applied, rather than the anhydrous crystallographic
      dimensions, for assessing the inter-domain orientations using the algorithms
      HYDROSUB and SOLPRO. Both chimeric IgG4 molecules were found to have open, rather
      than compact, structures, in agreement with the previous study on wild-type human
      IgG4. The insertion of a frictionless connector between the domains was
      necessary, however, for representing the cB72.3(gamma4A) chimera. It therefore
      appears that the inter-chain disulfide bonds act as physical constraints in the
      cB72.3(gamma4P) chimera, forcing the antibody domains together and producing a
      less elongated structure than that of cB72.3(gamma4A). The open structures
      produced for the two IgG4 chimeras showed similarity to those structures
      identified for murine IgG1 and IgG2a molecules through X-ray crystallography.

PMID- 12811431
TI  - Are the conformational dynamics and the ligand binding properties of myoglobin
      affected by exposure to microwave radiation?
AB  - The global uptake of mobile communication emphasizes the question about possible
      adverse consequences of the exposure to low-level radiofrequency radiation from
      mobile phones on human health as result of so-called "non-thermal effects". In
      order to state safety guidelines it seems appropriate to start by excluding, if
      possible, non-specific effects on structural and dynamic properties of
      fundamental biomolecules such as proteins. Proteins are flexible
      polyelectrolytes; thus, they are susceptible, in principle, to the action of
      electromagnetic fields. In this article, we investigated the effects of
      microwaves on structural and functional properties of Tunnus tynnus myoglobin at
      1.95 GHz, a frequency used by new wireless microwave communication systems. The
      protein solution was exposed for 2.5 h to 51 mW/g SAR (specific absorption rate)
      level. Measurements of absorption spectroscopy, circular dichroism and
      fluorescence emission decay in the frequency domain do not exhibit any influence
      of the radiation on the native structural state of protein macromolecules.

PMID- 12811432
TI  - Deformation of intracellular endosomes under a magnetic field.
AB  - We present a non-invasive method to monitor the membrane tension of intracellular
      organelles using a magnetic field as an external control parameter. By exploiting
      the spontaneous endocytosis of anionic colloidal ferromagnetic nanoparticles, we
      obtain endosomes possessing a superparamagnetic lumen in eukaryotic cells.
      Initially flaccid, the endosomal membrane undulates because of thermal
      fluctuations, restricted in zero field by the resting tension and the curvature
      energy of the membrane. When submitted to a uniform magnetic field, the
      magnetized endosomes elongate along the field, resulting in the flattening of the
      entropic membrane undulations. The quantification of the endosome deformation for
      different magnetic fields allows in situ measurement of the resting tension and
      the bending stiffness of the membrane enclosing the intracellular organelle.

PMID- 12811433
TI  - Sclerosing haemangioma arising within extralobar pulmonary sequestration.
AB  - Extralobar pulmonary sequestration is a rare anomaly of abnormal pulmonary tissue
      without any communication to the bronchial tree. Sclerosing haemangioma is a rare
      lung tumour, generally seen in middle-aged women. The combination of these two
      rare pathologies has not been previously reported. We describe the CT and CT
      angiographic findings of sclerosing haemangioma arising within an extralobar
      pulmonary sequestration in a 2-year-old girl.

PMID- 12811434
TI  - Congenital microgastria presenting as stridor.

PMID- 12811435
TI  - Ultrasonography and gastric emptying in children: validation of a sonographic
      method and determination of physiological and pathological patterns.
AB  - BACKGROUND: The association between gastric emptying and gastro-esophageal reflux
      (GER) has been widely recognised from scintigraphic studies. OBJECTIVE: A
      prospective study to (a) validate US as a means of measuring gastric emptying,
      (b) determine physiological patterns of gastric emptying and (c) measure gastric
      emptying in symptomatic refluxers. MATERIALS AND METHODS: Three cohorts were
      studied: (a) Ten babies in whom gastric emptying was measured by US and
      scintigraphy; (b) gastric emptying in 330 asymptomatic children aged between 15
      days and 10 years to determine physiological variations; and (c) gastric emptying
      in 552 children with GER, manifesting as vomiting or cardiorespiratory problems.
      RESULTS: US and scintigraphic techniques showed general concordance in 90% of
      cases. In the remaining 10%, discordant results were related to overlapping of
      duodenum and stomach during scintigraphy and shadowing of the gastric antrum by
      air during US. Tremendous variations were induced by change of feed volume or
      type of formula, underlining the need for a standardised procedure. Twenty-two
      percent of cases showed a peculiar 'plateau' which differed significantly from
      the physiological patterns. Most of these babies had esophagitis or acute life
      threatening events. CONCLUSIONS: Investigation of gastric emptying seems to be a
      key element in the assessment of children with 'pathological' GER. US is a safe
      and cheap alternative to scintigraphy for the assessment of gastric emptying.

PMID- 12811436
TI  - Rectal "ears".

PMID- 12811437
TI  - Complicated pyelogenic cyst.

PMID- 12811438
TI  - Angiographic follow-up of vertebrobasilar artery aneurysms treated with
      detachable coils.
AB  - Endovascular treatment of ruptured vertebrobasilar artery aneurysms with Gugliemi
      detachable coils (GDC) has become an alternative to surgery. Mid-term
      angiographic follow-up can now be reported. Of 111 vertebrobasilar aneurysms in
      110 patients we treated with GDC since 1992, 53 underwent angiography within 1
      year and 59 after more than 18 months. We did not achieve complete occlusion on
      initial treatment of 23 aneurysms (21%). Complications were observed in 19
      patients (17%), leading to permanent clinical disability in eight. Enlargement of
      the neck or reopening was seen in 12 (23%) of 53 aneurysms followed by
      angiography within 12 months. Documented recanalisation was treated in four (8%).
      Angiography was performed after 18-78 months in 59 patients, of whom nine,
      including three with initially incomplete occlusions, were retreated with GDC.
      Within the entire second observation period, three (5%) of the 59 patients had a
      further haemorrhage and were retreated with GDC. Rebleeding proved to be the only
      factor influencing the clinical outcome of retreated patients.

PMID- 12811439
TI  - Serial MRI of a mycotic aneurysm of the cavernous carotid artery.
AB  - Cerebral mycotic or infective aneurysms are a rare complication of infectious
      illness, and such aneurysms of the intracavernous portion of the internal carotid
      artery are rare. They have been described as a consequence of cavernous sinus
      infection in an immunocompromised host, but not previously in a renal transplant
      recipient. We present such a case with serial MRI showing progression from
      arterial narrowing to aneurysm formation. Transcranial Doppler sonography of the
      middle cerebral artery showed distal asymptomatic embolisation from the aneurysm.

PMID- 12811440
TI  - High incidence and spontaneous resolution of mastoid effusion after craniotomy on
      early postoperative magnetic resonance images.
AB  - Mastoid effusion is a poorly understood complication after craniotomy. The
      incidence and severity of postoperative mastoid effusion were retrospectively
      examined on postoperative magnetic resonance (MR) images to assess any
      association with craniotomy procedures, time course, and neuro-otological
      complications. We evaluated the early postoperative MR images (within 4 days of
      craniotomy) and medical records of 74 patients who underwent 77 operations for
      the treatment of various intracranial diseases from January 2000 to December
      2001. Mastoid effusion was classified into four grades: none, partial, moderate,
      and severe diffuse effusion in the mastoid air cells. Thirty-three follow-up MR
      images from 26 patients were also reviewed. Postoperative mastoid effusion
      occurred ipsilateral to the craniotomy site in 62 cases and contralateral in 56
      cases. Mastoid effusion was significantly more severe ipsilateral than
      contralateral to craniotomy with exposure of the mastoid air cells ( P<0.0001).
      There was no significant difference in severity between the contralateral and
      ipsilateral sides after craniotomy without mastoid air cell opening ( P=0.437).
      Mastoid effusion following craniotomy without exposure of mastoid air cells
      resolved within 3 months. However, otitis media with effusion developed in six
      patients with severe mastoid effusion ipsilateral to craniotomy with exposure of
      the mastoid air cells. Mastoid effusion frequently developed on both sides. Any
      grade of mastoid effusion on the ipsilateral side to craniotomy without exposure
      of mastoid air cells, or on the contralateral side, was asymptomatic or had a
      benign course, and disappeared within 3 months.

PMID- 12811441
TI  - Clinical, laboratory, psychiatric and magnetic resonance findings in patients
      with Sydenham chorea.
AB  - The objective of this study was to determine the clinical and laboratory
      characteristics, psychiatric manifestations and magnetic resonance imaging (MRI)
      findings in children and adolescents with Sydenham chorea (SyC). The imaging
      examination was repeated 1 year after the acute phase of SyC. There were 19
      patients with a mean age of 11.7 years and a predominance of females (79%);68%
      had generalized chorea and 53% moderate chorea. SyC presented as an isolated
      manifestation in 74%. No association between SyC and obsessive-compulsive
      disorder was found. Mental health problems were present in 45% of the patients.
      MRI analysis revealed persistent alterations in the caudate nucleus in three
      patients (16%), who presented recurrent episodes of chorea during the study. In
      one patient, MRI revealed the presence of nodular heteropathy close to the
      caudate nucleus region. We conclude that attention problems can be associated
      with acute clinical features of SyC and persistent alterations in the basal
      nuclei, evidenced by MRI, can be found in some patients who tend to suffer
      prolonged attacks and a greater number of recurrences.

PMID- 12811442
TI  - Analysis of human postural responses to recoverable falls.
AB  - We studied the kinematics and kinetics of human postural responses to
      "recoverable falls." To induce brief falling we used a Hold and Release (H&R)
      paradigm. Standing subjects actively resisted a force applied to their sternum.
      When this force was quickly released they were suddenly off balance. For a brief
      period, approximately 125 ms, until restoring forces were generated to shift the
      center of foot pressure in front of the center of mass, the body was in a forward
      fall acted on by gravity and ground support forces. We were able to describe the
      whole-body postural behavior following release using a multilink inverted
      pendulum model in a regime of "small oscillations." A three-segment model
      incorporating upper body, upper leg, and lower leg, with active stiffness and
      damping at the joints was fully adequate to fit the kinematic data from all
      conditions. The significance of our findings is that in situations involving
      recoverable falls or loss of balance the earliest responses are likely dependent
      on actively-tuned, reflexive mechanisms yielding stiffness and damping modulation
      of the joints. We demonstrate that haptic cues from index fingertip contact with
      a stationary surface lead to a significantly smaller angular displacement of the
      torso and a more rapid recovery of balance. Our H&R paradigm and associated model
      provide a quantifiable approach to studying recovery from potential falling in
      normal and clinical subjects.

PMID- 12811443
TI  - Early behavior of optokinetic responses elicited by transparent motion stimuli
      during depth-based attention.
AB  - When two visual patterns moving in different directions are superimposed on the
      same depth plane (transparent motion stimulus), observers perceive transparent
      surfaces sliding over each other on different depth planes. Simultaneously, an
      optokinetic response (OKR) occurs so that one of the visual patterns is
      stabilized on the retina. In this study, we investigated the early behavior of
      the OKR elicited by transparent motion stimuli while subjects focused their
      attention on either the near or far surface. Two random dot patterns were
      superimposed and moved in orthogonal or opposite directions. Subjects were
      instructed to report the motion direction of the surface on which their attention
      was focused. The mean latency of initiation of OKR in the case of motion in
      opposite directions (150 ms) was significantly longer than that in the case of
      motion in orthogonal directions (100 ms). In the case of motion in orthogonal
      directions, the distribution of directions of OKR during the initial period, from
      100 to 150 ms, was biased toward the mean direction of the two stimulus motions.
      After 160 ms, the eyes started to pursue a particular motion pattern of which the
      direction agreed with the far-perceived motion regardless of depth-based
      attention. Depth-based attention changed the direction of eye movements after 200
      ms and eventually made the eyes follow a pattern on which the attention was
      focused. These results suggest that pursuit eye movement immediately after 160 ms
      may determine perceptual depth order through change of retinal image motion,
      because the slow-moving retinal image may be perceived in the far depth plane.
      Following this process of determination of perceptual depth order, depth-based
      attention starts to affect OKR.

PMID- 12811445
TI  - Complexation of uranium(VI) with protocatechuic acid-application of iterative
      transformation factor analysis to EXAFS spectroscopy.
AB  - The speciation of 1 mM uranium(VI) in carbonate-free aqueous solutions of 50 mM
      protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid) was studied in the pH range
      of 4.0 to 6.8 using EXAFS spectroscopy. The uranium L(III)-edge EXAFS spectra
      were analyzed using a newly developed computer algorithm for iterative
      transformation factor analysis (FA). Two structural different uranium(VI)
      complexes were observed. The speciation in the pH range of 4.0 to 4.8 is
      dominated by a 1:2 or 1:3 uranium(VI)/PCA complex with bidentate coordination of
      the carboxyl group to the uranium(VI) moiety. Already at pH 4.6 significant
      amounts of a second species are formed. This uranium(VI) species contains two PCA
      ligands that are bound to the uranium via their neighboring phenolic hydroxyl
      groups under formation of five-member rings.

PMID- 12811444
TI  - Morphological alterations in the occipital cortex of aged rats with impaired
      memory: a Golgi-Cox study.
AB  - This study investigated a possible link between morphological alterations of
      pyramidal neurons in layer V of the occipital cortex and the degree of spatial
      memory impairment in aged rats. Measurements of cortical thickness, density of
      dendritic branching, and spine counts were carried out in young adult (5 months
      old) and aged (26 months old) Long-Evans female rats on Golgi-Cox silver-stained
      material. Using the water-maze task, well- and poorly performing rats were
      distinguished statistically on the basis of their reference-memory scores. When
      subsequently compared with young rats or to aged rats with good performances, the
      well-performing rats had a reduced cortical thickness and exhibited weaker high
      order branching of basal dendrites on their pyramidal neurons. When dendritic
      spines were counted on a 50-microm-long straight portion of a basal dendrite, no
      difference was observed between young and aged rats. Our results suggest that
      structural alterations affecting pyramidal neurons in the occipital cortex of
      aged rats may contribute to spatial memory impairment. Indeed, in a subpopulation
      of well-performing aged rats, these structural alterations were less marked than
      in the population of bad performers.

PMID- 12811446
TI  - Isolation and determination of p-hydroxybenzoylcholine in traditional Chinese
      medicine Semen sinapis Albae.
AB  - A special component is isolated from Semen sinapis Albae (white mustard seed), a
      traditional Chinese medicine. According to the physical and chemical
      investigation and spectroscopic identification, this component can be known as p
      hydroxybenzoylcholine bisulfate, a choline base. This component in the drug is
      also determined by RP-HPLC. A reversed-phase C(18) column is used to separate the
      p-hydroxybenzoylcholine with an eluent of methanol-0.05 mol/L monopotassium
      phosphate solution (30:70) (adjusted by phosphoric acid to pH 3.6) at the flow
      rate of 0.5 mL/min. Detection is carried out with a UV detector operated at 285
      nm, and the column temperature is 25 degrees C. It reveals that there is 0.021%
      (w/w) of p-hydroxybenzoylcholine bisulfate in Semen sinapis Albae and 0.037%
      (w/w) in stir-baked Semen sinapis Albae.

PMID- 12811447
TI  - Three useful bromimetric methods for the determination of salbutamol sulfate.
AB  - Three different methods developed for the determination of salbutamol sulfate
      (SBS), in pure drug form and in dosage forms, are discussed. The methods are
      based on the oxidation-bromination reaction of the drug by bromine generated in
      situ by the interaction of bromate with bromide in acid medium. In titrimetry the
      drug is titrated directly with bromate in the presence of a large excess of
      bromide and in sulfuric acid medium using methyl red as indicator.
      Spectrophotometry is based on addition of a measured excess of bromate-bromide
      mixture to the sample solution in sulfuric acid medium followed by the estimation
      of surplus bromine by reacting it with a definite amount of methyl orange dye and
      measuring the absorbance at 510 nm. The amount of bromate reacting corresponds to
      the sample content. The kinetic method depends on the linear relationship between
      the concentration of the drug and time for oxidation and bromination as indicated
      by the bleaching of the methyl orange acid colour by the bromine generated in
      situ. Titrimetry is applicable in the 2-20 mg range. In spectrophotometry, Beer's
      law is obeyed in the 0.5-5.0 microg mL(-1) range whereas concentrations in the
      5.0-25.0 microg mL(-1) range can be determined by the kinetic method. The effect
      of common excipients and additives in tablets is discussed. The procedures have
      been successfully applied to dosage forms; the results agree well with those
      obtained by use of a reference method. The methods can be used to determine SBS
      at mg or nicrog levels.

PMID- 12811448
TI  - A liquid chromatography/electrospray ionization-tandem mass spectrometry method
      for quantification of specific organophosphorus pesticide biomarkers in human
      urine.
AB  - Organophosphorus pesticides are commonly used in both agricultural and
      residential settings. The widespread use of these chemicals makes it almost
      impossible for humans to avoid exposure. In order to determine background human
      exposure, there is a need for fast, reliable, and sensitive analytical methods.
      We have developed a sensitive method to quantify specific biomarkers of the
      organophosphorus pesticides acephate, azinphos, chlorpyrifos, coumaphos,
      diazinon, isazofos, malathion, methamidophos, parathion and pirimiphos or their
      O,O-dimethyl analogues in human urine, as their selective metabolites or as the
      intact pesticide. Isotopically labeled internal standards were used for eight of
      the analytes. The use of labeled internal standards in combination with high
      performance liquid chromatography electrospray ionization-tandem mass
      spectrometry provided a high degree of specificity. Repeated analysis of urine
      samples fortified with high and low concentrations of the analytes gave relative
      standard deviations (RSD) of less than 10% for the analytes with an isotopically
      labeled standard. Analytes without isotopically labeled standards had higher RSD.
      For all compounds except methamidophos and acephate, the recoveries were greater
      than 70%. The limits of quantification for most of the analytes were in the range
      of 0.1 to 1 ng/mL. We detected concentrations of most of these pesticides and/or
      their metabolites in urine samples from non-occupationally exposed persons using
      our method. Our frequencies of detection for the analytes measured ranged from 1%
      to 98%.

PMID- 12811449
TI  - Analysis of the cleaved topaz (001) surface.
AB  - We report on the first study of the cleaved (001) topaz surface and the
      characterization of the chemical composition and atomic arrangement of the
      surface. We conclude that there is strong evidence for a hydroxyl group
      termination appropriate for further chemical reactions. The surface itself is
      easily accessible, atomically flat and suitable for potential technological
      applications.

PMID- 12811450
TI  - Polymeric FAD used as enzyme-friendly mediator in lactate detection.
AB  - We present the fabrication and properties of lactate biosensors. The novel
      feature is the use of polymerized flavin adenine dinucleotide (FAD) as mediator
      for electron transfer. The biosensors were prepared using lactate dehydrogenase
      (LDH), lactate oxidase (LOX), or baker's yeast (BY) immobilized at the surface of
      the electrode. The sensors using purified enzymes showed good sensitivity,
      linearity, and stability. The sensitivity of the BY electrodes was slightly
      lower. The advantages of this type of sensors are discussed in connection with
      potential applications.

PMID- 12811451
TI  - Recent developments in methods of chemical analysis in investigations of firearm
      related events.
AB  - A review of recent (approximately the last ten years) developments in the methods
      used for chemical analysis in investigations of firearm-related events is
      provided. This review discusses:examination of gunshot (primer) residues (GSR)
      and gunpowder (propellant) residues on suspects and their clothing;detection of
      firearm imprints on the hands of suspects;identification of the bullet entry
      holes and estimation of shooting distance;linking weapons and/or fired ammunition
      to the gunshot entries, and estimation of the time since discharge.

PMID- 12811452
TI  - Determination of iridoid glycosides in larvae and adults of butterfly Melitaea
      cinxia by partial filling micellar electrokinetic capillary chromatography
      electrospray ionisation mass spectrometry.
AB  - The iridoid glycosides, methyl catalpol, asperuloside, verbenalin, cinnamoyl
      catalpol, catalpol and aucubin, were studied from both larvae and adults of
      butterfly Melitaea cinxia. Special emphasis in the study was put on finding a
      correlation between the iridoid glycoside content in butterflies and plants. An
      optimised partial filling micellar electrokinetic capillary chromatographic
      electrospray ionisation mass spectrometric (PF-MECC-ESI-MS) method was employed
      for the separation and identification of the six iridoid glycosides. In this
      work, the isolation and determination of catalpol and aucubin from extracts of
      both larvae and adults of Melitaea cinxia butterflies is demonstrated. The PF
      MECC-ESI-MS method, using the [M+Na]+, [M+Li]+ and/or [M+NH(4)]+ adducts in ESI
      MS, was used for quantification of aucubin and catalpol in the insects. In
      addition, the identification of all analytes was attempted by direct infusion
      MS/MS analysis. LOQ values for the iridoid glycosides varied between 10 mg/l (for
      verbenalin) to 50 mg/l (for catalpol and aucubin) corresponding to 0.1% of the
      samples dry mass. A correlation was noticed between the concentrations of iridoid
      glycosides in plants and the concentrations in larvae feeding on them.

PMID- 12811453
TI  - Rapid fluorimetric assay for primary amine groups in water samples.
AB  - Bond Elut C(18) solid-phase extraction cartridges were used for pre-concentration
      followed by derivatization with o-phthaldialdehyde-N-acetylcysteine (OPA-NAC) of
      primary amines in water. Optimal conditions were: conditioning the cartridges
      with borate buffer pH 10.4, retention of the primary amines, addition of the OPA
      NAC(3.7 mmol L(-1)) 1:1 molar ratio and borate buffer pH 8, elution of the
      isoindol with MeOH-borate buffer (9:1) pH 10.2 and fluorescence measurement. The
      equations of the calibration graphs for methylamine, ethylamine, propylamine,
      butylamine, pentylamine, and beta-phenylethylamine at lambda(excitation)=330 nm
      and lambda(emission)=440 nm, in the optimal conditions are presented. The solid
      phase extraction procedure improved ten times the detection limits of the
      solution derivatization. Those values are in the 0.01-0.06 mg L(-1) interval in
      function of the amine. Also, it is possible to estimate the total primary
      aliphatic amine concentration in water, expressed as molar concentration of 
      NH(2) group or -NH(2)-N mg L(-1). On the basis of these studies, the method was
      applied for the determination of primary amino groups in tap, ground, factory and
      source water samples.

PMID- 12811454
TI  - Evalution of sequential extractions on dry and wet sediments.
AB  - A five-step sequential extraction procedure was applied on dried and wet
      Ballastplaat Scheldt estuary sediments. When wet (fresh) sediments were used, all
      sample handling up to the 3rd extraction step, inclusive, was carried out under
      inert atmosphere. The repeatability of the procedure was very good on dry
      samples. For Fe as for Mn, RSD values are lower than 4%, except for Mn in the
      fifth extraction step where a spread of 10% is observed. The observed RSDs for Pb
      are of the same order of magnitude as those for Mn. On wet samples the spread of
      the results is higher than on dried ones. The highest RSDs observed for Fe amount
      to 20%, for Mn to 15% but for Pb an RSD of up to 44% was found. Better
      homogenization of the solid sediment part of lyophilized sediments and different
      porosities of wet sediment sub-samples may be the explanation. These results also
      indicated that drying/oxidizing of the sediment sample causes a shift from less
      available/mobile metal fractions to more available/mobile fractions. The Mn and
      Fe oxyhydroxide spikes added to a wet sediment sample were recovered between
      100+/-10%. The results obtained after changing the sequence of the extraction
      steps (multiple rotations and inversions were tested) corroborated the
      progressive increase in the aggressive nature of the extraction solutions in our
      standard scheme. Although there is also no need to change the ratio volume of
      extractant to amount of sediment, increasing the number of extraction repetitions
      in steps 1 to 3 resulted, for some of those extraction steps, in a partially
      modified analyte distribution. Finally the method was applied to sandy and muddy
      sediment cores of the Scheldt estuary and revealed clear differences between
      metal distributions in both types of sediment.

PMID- 12811455
TI  - X-ray microscopy: methods and perspectives.

PMID- 12811456
TI  - Determination of Cr (in small quantities) by adsorptive stripping voltammetry: a
      comparative study of square wave versus differential pulse.
AB  - The usefulness of an analytical method must be measured according to its
      practical application possibilities. A comparative study has been carried out
      here between the SW (working in an open atmosphere) and DP (working with de
      aerated solutions) variants of catalytic-stripping adsorptive voltammetry applied
      to the determination of chromium traces in triethylenetetraminehexaacetic acid
      (TTHA) medium. In order to optimise the analytical signal, accumulation
      potential, nitrate ion concentration, pH, and TTHA concentration parameters were
      evaluated. Four linearity ranges were established within the interval 0.5-2000
      nmol L(-1) chromium concentration in the cell, each with the recommended
      accumulation time. Quality parameters such as repeatability, linear regression,
      validity limits, precision, and sensitivity were evaluated. The SW variant is
      significantly advantageous when the chromium concentration in cell is less than
      10 nmol L(-1) and even more if analysis time, cost, and being able to work in an
      open atmosphere are considered. The results are comparable to those obtained
      using GTAAS. Employing a CRM (tomato leaves), the accuracy is 1-4%. The proposed
      procedure, using tree leaves as samples, has been successfully tested for the
      possible monitoring of chromium contamination of the atmosphere.

PMID- 12811457
TI  - Current research activity in biosensors.
AB  - Biosensors consist of a molecular recognition element and a transducer. Since the
      first biosensor was developed by Updike and Hicks many biosensors and their
      associated techniques have been studied and developed. In this review current
      research activity on the fundamentals and applications of biosensors is
      summarized. In discussion of the former, molecular recognition elements,
      techniques and tools for biosensor construction, and basic biosensor devices are
      introduced. Coverage of the latter includes description of biosensors for
      environmental, food, and clinical fields. Chemical sensors developed in our
      laboratory for environmental monitoring are also described. This review mainly
      summarizes work performed by our group and by our colleagues, and refers to the
      main review articles summarizing each field of biosensor research in recent
      years.

PMID- 12811458
TI  - Characterization of the sorption of uranium(VI) on different complexing resins.
AB  - The sorption of uranium(VI) on two cationic resins containing different
      complexing groups, the iminodiacetic resin Chelex 100 and the weak carboxylic
      resin Amberlite CG-50, was investigated. The Gibbs-Donnan model was used to
      describe and to predict the sorption through the determination of the intrinsic
      complexation constants. These quantities, even though non-thermodynamic,
      characterize the sorption as being independent of experimental conditions. The
      sorption mechanism of the metal on the complexing resins was also studied by
      adding a competitive soluble ligand that shifts the sorption curves to higher pH
      values. The ligand competes with the resin for the complexation with the metal
      ion. Uranium is also strongly sorbed on Chelex 100 at very acid pH, through
      formation of two complexes in the resin phase: ML with log beta(110i)=-1.16, in
      more acidic solution, and ML(2 )with log beta(120i)=-5.72. Only the presence of
      the competitive ligand in solution makes the determination of the second complex
      possible. Also on Amberlite CG-50 the sorption is strong and involves the
      formation of the complex ML(2), in more acidic solution, with log beta(120i)=
      3.16. In the presence of the ligand EDTA, the complex ML(2)(OH)(2 )was
      characterized with log beta(12-2i)=-5.15. In all the experiments the hydrolysis
      reaction in the aqueous phase was quantitatively considered.

PMID- 12811459
TI  - Analytical characteristics and sensitivity mechanisms of electrolyte-insulator
      semiconductor system-based chemical sensors-a critical review.
AB  - Recent trends in research and development of electrolyte-insulator-semiconductor
      (EIS) field-effect chemical sensors (ion-selective field-effect transistors,
      light-addressable potentiometric sensors, capacitive EIS-sensors) with inorganic
      gate insulators (oxide, nitride and chalcogenide films) are reviewed. Physical
      properties of EIS systems and basic mechanisms of their chemical sensitivity are
      examined. Analytical characteristics and sensing mechanisms of EIS pH sensors
      with oxide and nitride films, as well as metal ions sensors with chalcogenide
      films, are critically discussed. Prospects of future research on EIS field-effect
      biosensors are briefly outlined.

PMID- 12811460
TI  - Analysis and comparison of glass fragments by laser ablation inductively coupled
      plasma mass spectrometry (LA-ICP-MS) and ICP-MS.
AB  - The discrimination potential of Laser Ablation Inductively Coupled Plasma Mass
      Spectrometry (LA-ICP-MS) is compared with previously reported solution ICP-MS
      methods using external calibration (EC) with internal standardization and a newly
      reported solution isotope dilution (ID) method for the analysis of two different
      glass populations. A total of 91 different glass samples were used for the
      comparison study; refractive index and elemental composition were measured by the
      techniques mentioned above. One set consisted of 45 headlamps taken from a
      variety of automobiles that represents a range of 20 years of manufacturing
      dates. A second set consisted of 46 automotive glasses (side windows, rear
      windows, and windshields) representing casework glass from different vehicle
      manufacturers over several years. The element menu for the LA-ICP-MS and EC-ICP
      MS methods include Mg, Al, Ca, Mn, Ce, Ti, Zr, Sb, Ga, Ba, Rb, Sm, Sr, Hf, La,
      and Pb. The ID method was limited to the analysis of two isotopes each of Mg, Sr,
      Zr, Sb, Ba, Sm, Hf, and Pb. Laser ablation analyses were performed with a Q
      switched Nd:YAG, 266 nm, 6 mJ output energy laser. The laser was used in depth
      profile mode while sampling using a 50 microm spot size for 50 sec at 10 Hz (500
      shots). The typical bias for the analysis of NIST 612 by LA-ICP-MS was less than
      5% in all cases and typically better than 5% for most isotopes. The precision for
      the vast majority of the element menu was determined generally less than 10% for
      all the methods when NIST 612 was measured (40 microg x g(-1)). Method detection
      limits (MDL) for the EC and LA-ICP-MS methods were similar and generally reported
      as less than 1 microg x g(-1) for the analysis of NIST 612. While the solution
      sample introduction methods using EC and ID presented excellent sensitivity and
      precision, these methods have the disadvantages of destroying the sample, and
      also involve complex sample preparation. The laser ablation method was simpler,
      faster, and produced comparable discrimination to the EC-ICP-MS and ID-ICP-MS. LA
      ICP-MS can offer an excellent alternative to solution analysis of glass in
      forensic casework samples.

PMID- 12811461
TI  - Development of microsatellite markers in Cannabis sativa for DNA typing and
      genetic relatedness analyses.
AB  - Microsatellite markers were developed for Cannabis sativa L. (marijuana) to be
      used for DNA typing (genotype identification) and to measure the genetic
      relationships between the different plants. Twelve different oligonucleotide
      probes were used to screen an enriched microsatellite library of Cannabis sativa
      in which 49% of the clones contained microsatellite sequences. Characterization
      of microsatellite loci in Cannabis revealed that GA/CT was the most abundant
      class of the isolated microsatellites representing 50% overall followed by
      GTT/CAA, AAG/TTC, and GAT/CTA representing 16%, 15%, and 10%, respectively.
      Eleven polymorphic STR markers were developed, three derived from dinucleotide
      motifs and eight from trinucleotide motifs. A total of 52 alleles were detected
      averaging 4.7 alleles/locus. The expected heterozygosity of the eleven loci
      ranged between 0.368 and 0.710 and the common probability of identical genotypes
      was 1.8 x 10(-7). The loci identified 27 unique profiles of the 41 Cannabis
      samples. The 11 microsatellite markers developed in this study were found to be
      useful for DNA typing and for assessing genetic relatedness in Cannabis.

PMID- 12811462
TI  - Array biosensor for detection of toxins.
AB  - The array biosensor is capable of detecting multiple targets rapidly and
      simultaneously on the surface of a single waveguide. Sandwich and competitive
      fluoroimmunoassays have been developed to detect high and low molecular weight
      toxins, respectively, in complex samples. Recognition molecules (usually
      antibodies) were first immobilized in specific locations on the waveguide and the
      resultant patterned array was used to interrogate up to 12 different samples for
      the presence of multiple different analytes. Upon binding of a fluorescent
      analyte or fluorescent immunocomplex, the pattern of fluorescent spots was
      detected using a CCD camera. Automated image analysis was used to determine a
      mean fluorescence value for each assay spot and to subtract the local background
      signal. The location of the spot and its mean fluorescence value were used to
      determine the toxin identity and concentration. Toxins were measured in clinical
      fluids, environmental samples and foods, with minimal sample preparation. Results
      are shown for rapid analyses of staphylococcal enterotoxin B, ricin, cholera
      toxin, botulinum toxoids, trinitrotoluene, and the mycotoxin fumonisin. Toxins
      were detected at levels as low as 0.5 ng mL(-1).

PMID- 12811463
TI  - High-performance liquid chromatographic determination of diltiazem in human
      plasma after solid-phase and liquid-liquid extraction.
AB  - A selective, sensitive, and accurate high-performance liquid chromatographic
      method for determination of diltiazem in plasma samples has been developed and
      validated. The effects of mobile phase composition, buffer concentration, mobile
      phase pH, and concentration of organic modifiers on retention of diltiazem and
      internal standard were investigated. Solid-phase and liquid-liquid extraction
      were examined and proposed for isolation of the drug and elimination of
      endogenous plasma interferences. A 5 microm Lichrocart Lichrospher 60 RP-select B
      chromatographic column was used; the mobile phase was acetonitrile-0.025 mol L(
      1) KH(2)PO(4) (pH 5.5), 35:65 ( v/ v) at a flow-rate of 1.5 mL min(-1). The
      detection wavelength was 215 nm. The calibration plots were linear in the
      concentration range 20.0-500.0 ng mL(-1). The method has been implemented to
      monitor diltiazem levels in patient samples.

PMID- 12811464
TI  - Effect of bupropion on nicotine self-administration in rats.
AB  - RATIONALE AND OBJECTIVE: The mechanisms underlying the therapeutic efficacy of
      bupropion as a smoking cessation agent are unknown. Bupropion inhibits monoamine
      uptake as well as neuronal nicotinic receptor (nAChR) function. The present study
      compared effects of bupropion on nicotine self-administration to those of other
      stimulant drugs (methamphetamine and apomorphine) that lack nAChR activity in
      order to determine its mechanism of action. To determine the specificity of
      bupropion-induced changes in nicotine self-administration, the ability of
      bupropion to alter sucrose-maintained responding or amphetamine self
      administration was determined. METHODS: In nicotine and amphetamine self
      administration and sucrose-maintained responding experiments, rats responded for
      nicotine (0.01 or 0.02 mg/kg per infusion, IV), amphetamine (0.2 mg/kg per
      infusion, IV) and sucrose pellets (45 mg), respectively, on a fixed ratio 5
      schedule. Once responding stabilized, rats were pretreated 15 min before the
      session with bupropion (1-78 mg/kg) or vehicle. The ability of methamphetamine
      (0.3-3 mg/kg) or apomorphine (0.01-0.2 mg/kg) to alter responding for nicotine
      (0.02 mg/kg per infusion, IV) was determined. RESULTS: Bupropion produced a
      biphasic dose-response pattern at both nicotine infusion doses, increasing
      infusions at low bupropion doses and decreasing infusions at high bupropion
      doses. Methamphetamine produced a similar biphasic pattern, whereas apomorphine
      only decreased nicotine infusions at high doses. Bupropion dose-dependently
      decreased responding for sucrose and amphetamine. CONCLUSIONS: These results
      suggest that high bupropion doses decrease responding nonspecifically; whereas
      low bupropion doses selectively increase responding for nicotine. The increase in
      nicotine self-administration is likely due to inhibition of dopamine and
      norepinephrine transporters, combined with inhibition of nAChRs.

PMID- 12811465
TI  - Ultrastructural changes induced by the des-F(6)-quinolone garenoxacin (BMS
      284756) and two fluoroquinolones in Achilles tendon from immature rats.
AB  - Garenoxacin is a des-(6)-fluoroquinolone exhibiting a comparatively low
      chondrotoxic potential in juvenile animals. We studied the effects of the drug on
      Achilles tendons in immature Wistar rats treated by oral intubation once daily
      (1) for 5 consecutive days from postnatal week 4 onward at doses of 0 (vehicle),
      200 and 600 mg/kg body weight (b wt), and (2) for 21 consecutive days from
      postnatal day 4 onward at doses of 0 (vehicle), 80, 240 or 300 mg/kg b wt;
      ofloxacin or ciprofloxacin were used as comparators. Achilles tendon specimens
      were studied by electron microscopy. In comparison with vehicle-treated controls,
      ultrastructural changes were detectable in all samples from the garenoxacin-,
      ofloxacin-, or ciprofloxacin-treated rats (one animal per group). We found
      degenerative changes such as multiple vacuoles and large vesicles in the
      cytoplasm of tenocytes that resulted from swelling and dilatation of cell
      organelles (mitochondria, endoplasmic reticulum), densified nuclei and clumped
      chromatin; furthermore, cells that detached from the extracellular matrix, a
      general decrease of the fibril diameter and an increase in the distance between
      the collagenous fibrils were recognizable. The degree of changes increased with
      increasing doses. It remains unclear what these findings mean with respect to a
      possible risk in juvenile patients treated with garenoxacin or the other
      quinolones, but our results underline the fact that, in principle, this des-(6)
      fluoroquinolone also has the potential to cause changes in connective tissue
      structures.

PMID- 12811466
TI  - Identification of a gene cluster encoding meilingmycin biosynthesis among
      multiple polyketide synthase contigs isolated from Streptomyces nanchangensis
      NS3226.
AB  - A cluster encoding genes for the biosynthesis of meilingmycin, a macrolide
      antibiotic structurally similar to avermectin and milbemycin alpha11, was
      identified among seven uncharacterized polyketide synthase gene clusters isolated
      from Streptomyces nanchangensis NS3226 by hybridization with PCR products using
      primers derived from the sequences of aveE, aveF and a thioesterase domain of the
      avermectin biosynthetic gene cluster. Introduction of a 24.1-kb deletion by
      targeted gene replacement resulted in a loss of meilingmycin production,
      confirming that the gene cluster encodes biosynthesis of this important
      anthelminthic antibiotic compound. A sequenced 8.6-kb fragment had aveC and aveE
      homologues ( meiC and meiE) linked together, as in the avermectin gene cluster,
      but the arrangement of aveF ( meiF) and the thioesterase homologues differed. The
      results should pave the way to producing novel insecticidal compounds by
      generating hybrids between the two pathways.

PMID- 12811467
TI  - Xylose metabolism in the anaerobic fungus Piromyces sp. strain E2 follows the
      bacterial pathway.
AB  - The anaerobic fungus Piromyces sp. strain E2 metabolizes xylose via xylose
      isomerase and d-xylulokinase as was shown by enzymatic and molecular analyses.
      This resembles the situation in bacteria. The clones encoding the two enzymes
      were obtained from a cDNA library. The xylose isomerase gene sequence is the
      first gene of this type reported for a fungus. Northern blot analysis revealed a
      correlation between mRNA and enzyme activity levels on different growth
      substrates. Furthermore, the molecular mass calculated from the gene sequence was
      confirmed by gel permeation chromatography of crude extracts followed by activity
      measurements. Deduced amino acid sequences of both genes were used for
      phylogenetic analysis. The xylose isomerases can be divided into two distinct
      clusters. The Piromyces sp. strain E2 enzyme falls into the cluster comprising
      plant enzymes and enzymes from bacteria with a low G+C content in their DNA. The
      d-xylulokinase of Piromyces sp. strain E2 clusters with the bacterial d
      xylulokinases. The xylose isomerase gene was expressed in the yeast Saccharomyces
      cerevisiae, resulting in a low activity (25+/-13 nmol min(-1)mg protein(-1)).
      These two fungal genes may be applicable to metabolic engineering of
      Saccharomyces cerevisiae for the alcoholic fermentation of hemicellulosic
      materials.

PMID- 12811468
TI  - Response to van Saene et al.'s comment on "Prevention of severe Candida
      infections in non-neutropenic, high-risk, critically ill patients".

PMID- 12811469
TI  - Intercellular signalling within vascular cells under high D-glucose involves free
      radical-triggered tyrosine kinase activation.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus is associated with endothelial dysfunction in
      human arteries due to the release of superoxide anions (*O(2)(-)) that was found
      to occur predominantly in smooth muscle cells (SMC). This study was designed to
      elucidate the impact of high glucose concentration mediated radical production in
      SMC on EC. Pre-treatment of vascular SMC with increased D-glucose enhanced
      release of *O(2)(-). METHODS: Microscope-based analyses of intracellular free
      Ca(2+) concentration (fura-2), immunohistochemistry (f-actin) and tyrosine kinase
      activity were performed. Furthermore, RT-PCR and Western blots were carried out.
      RESULTS: Interaction of EC with SMC pre-exposed to high glucose concentration
      yielded changes in endothelial Ca(2+) signalling and polymerization of f-actin in
      a concentration-dependent and superoxide dismutase (SOD) sensitive manner. This
      interaction activated endothelial tyrosine kinase(s) but not NFkappaB and AP-1,
      while SOD prevented tyrosine kinase stimulation but facilitated NFkappaB and AP-1
      activation. Erbstatin, herbimycin A and the src family specific kinase inhibitor
      PP-1 but not the protein kinase C inhibitor GF109203X prevented changes in
      endothelial Ca(2+) signalling and cytoskeleton organization induced by pre
      exposure of SMC to high glucose concentration. Adenovirus-mediated expression of
      kinase-inactive c-src blunted the effect of pre-exposure of SMC to high glucose
      concentration on EC. CONCLUSIONS/INTERPRETATION: These data suggest that SMC
      derived *O(2)(-) alter endothelial cytoskeleton organization and Ca(2+)
      signalling via activation of c-src. The activation of c-src by SMC-derived
      radicals is a new concept of the mechanisms underlying vascular dysfunction in
      diabetes.

PMID- 12811470
TI  - Multinational study of major breast milk carotenoids of healthy mothers.
AB  - BACKGROUND: Carotenoids in serum vary between countries and within populations
      with evidence suggesting a qualitative relationship to diet. Breast milk
      carotenoids furnish a source of vitamin A and potentially provide
      immunoprotection and other health benefits for infants. There have been numerous
      studies of milk carotenoid concentrations in undernourished populations; however,
      carotenoid concentrations have not previously been compared in populations of
      well-nourished mothers. AIM OF STUDY: To compare concentrations of five major
      carotenoid groups: alpha-carotene, beta-carotene, beta-cryptoxanthin,
      lutein/zeaxanthin, and lycopene in breast milk of healthy women from Australia,
      Canada, Chile, China, Japan, Mexico, the Philippines, the United Kingdom, and the
      United States, and to qualitatively compare patterns of dietary intake with milk
      carotenoid concentrations. METHODS: Breast milk collected from healthy lactating
      women was analyzed for concentrations of five carotenoids and retinol and
      quantitated relative to total milk lipid. All determinations were performed in a
      single research laboratory using standardized methodology. Mothers consumed their
      usual diets and provided a single 24-h dietary recall. RESULTS: Breast milk
      carotenoid concentrations varied greatly among countries, with the greatest
      differences in beta-cryptoxanthin (approximately 9-fold) and the least in alpha
      carotene and lycopene (approximately 3-fold). Breast milk retinol concentrations
      varied approximately 2-fold across countries. The provitamin A carotenoids alpha
      carotene, beta-carotene, and beta-cryptoxanthin as a group accounted for > 50 %
      of the carotenoids measured. Total breast milk carotenoids were highest in
      Japanese and lowest in Philippine mothers. Breast milk beta-carotene
      concentrations were highest in Chile and lowest in the Philippines. CONCLUSIONS:
      Patterns of breast milk carotenoids were unique to each country and qualitative
      patterns reflected the dietary carotenoid supply.

PMID- 12811471
TI  - Lower serum leptin levels in female students of the nutritional sciences with
      eating disorders.
AB  - BACKGROUND: Evidence has accumulated that in both acutely ill and recovered
      patients with either anorexia or bulimia nervosa circulating leptin levels (LL)
      are lower than in controls matched for body mass index (BMI; kg/m(2)). It is
      unknown if these lower leptin levels represent a state or trait marker. AIM OF
      THE STUDY: We aimed to confirm the lowered leptin levels in eating disordered
      females and to identify underlying mechanisms. METHODS: We screened 181 female
      students of the nutritional sciences for eating disorders with the respective
      module of the M-Composite International Diagnostic Interview and the Cognitive
      Restraint scale of the Three Factor Eating Questionnaire. The physical assessment
      included determinations of BMI, body composition and LL. Each case fulfilling
      lifetime DSM-IV criteria for an eating disorder was BMI matched to two controls.
      We used a multivariate mixed regression model to evaluate if the observed
      difference in lg(10)-leptin level between cases and controls is actually due to
      the influence of restrained eating and/or previous weight loss after adjustment
      for BMI and percent body fat. RESULTS: In accordance with our hypothesis the 32
      (17.7 %) cases had a lower serum lg(10)-leptin level than the 64 BMI matched
      controls (one-sided p < 0.001). We were not able to detect an influence of
      restrained eating or previous weight loss. CONCLUSIONS: We confirm that females
      with a lifetime history of an eating disorder have lower LL. We were not able to
      identify an underlying mechanism. Similar to most previous studies we found a
      high rate of eating disorders among female students of nutritional sciences.

PMID- 12811472
TI  - Lipolysis induced by leptin in rat adipose tissue from different anatomical
      locations.
AB  - The aim of the present work is to compare the lipolytic response of three fat
      depots (subcutaneous, epididymal and perirenal) to leptin under in vitro
      conditions in rats. Moreover an assessment of the potential differences between
      young and mature rats in terms of the response of these tissues to leptin is
      made. Adipocytes from 6- and 20-wk-old rats were isolated by collagenase
      digestion and incubated in vitro both in the absence and the presence of either
      leptin (10(-12)-10(-6) M) or isoproterenol (10(-6) M). Lipolysis was measured by
      the release of glycerol into the incubation medium over 2 hours of incubation.
      Adipocytes responded in a dose-dependent manner to leptin concentrations ranging
      from 10(-12) M to 10(-6) M. The lowest leptin concentration inducing a
      significant lipolytic effect was 10(-9) M in all tissues. No significant
      differences in the effect of the maximal concentration of leptin (10(-6) M) were
      observed among tissues for either age. The lipolytic effect of isoproterenol (10(
      6) M) was significantly reduced in adipose tissues from mature rats; in contrast
      no significant differences in the effect of leptin (10(-6) M) were observed
      between young and mature rats. In summary, no anatomical-specific differences
      exist in the response of rat adipose tissue to lipid mobilization induced by
      leptin. Furthermore, this leptin action is not decreased in mature rats compared
      with young ones.

PMID- 12811474
TI  - Height and weight of German primary school children in the Family Intervention
      Trial (FIT) Erlangen.
AB  - Many anthropometric reference data for children are based on studies conducted up
      to 40 years ago. We assessed height and weight distribution of a population of
      German primary school children and compared the results with national and
      international reference data. In February 1998 weight and height were measured in
      427 first grade school children (195 boys, 232 girls) aged 6 to 7 years who
      participated in the family intervention trial Erlangen. Compared to studies in
      the 1980s, weight showed a marked but height only a minimal increase. Mean weight
      for-height is similar to previously published reference data, but upper
      percentile values are much higher. Mean weight-for-height and the proportion of
      overweight children are similar for children of German and of foreign origin. We
      conclude that overweight and obesity have clearly increased in primary school
      children in recent years.

PMID- 12811473
TI  - Non-esterified plant sterols solubilized in low fat milks inhibit cholesterol
      absorption--a stable isotope double-blind crossover study.
AB  - BACKGROUND: The cholesterol absorption inhibiting properties of plant sterols in
      milks are unknown. The milk fat globule membrane components may enhance the
      absorption of cholesterol and could make plant sterols less efficient in this
      complex matrix. AIM OF THE STUDY: To evaluate in hypercholesterolemic men the
      cholesterol absorption inhibiting properties of verified properly solubilized,
      non-esterified plant sterols in partly vegetable oil containing milks. METHODS:
      The plant sterols in milk were determined to be properly solubilized, and to have
      effective in vitro functionality. Sixteen hypercholesterolemic adult men (initial
      total cholesterol 5.8-8.6 mM) then consumed milk containing sterols (1.8 g of non
      esterified pure plant sterols/d) and control milk, alternatively, during two 6
      day periods in a double blind cross over design. During the trial, cholesterol
      absorption was evaluated from the ratio of plasma isotopic enrichment of [26, 26,
      26, 27, 27, 27-(2)H(6)]cholesterol from oral intake (35.6 +/- 0.2 micromol, +/-
      SEM) over enrichment of [23, 24, 25, 26, 27-(13)C(5)]cholesterol from intravenous
      injection (77.9 +/- 0.5 micromol). RESULTS: Plant sterols in low fat milks
      contained very few crystals > 11 microm in the presence and absence of bile salts
      and lysophospholipids, and inhibited cholesterol uptake in Caco-2 cell. This
      assured that the sterols were properly solubilized prior to the clinical trial.
      In the clinical study, compliance of volunteers was excellent. After tracer
      injections (72 h), the plasma [(2)H] and [(13)C] isotopic enrichments changed
      from 0.024 +/- 0.001 and 0.072 +/- 0.003 MPE (control) to 0.015 +/- 0.001 and
      0.074 +/- 0.002 MPE during sterol treatment, respectively. Cholesterol absorption
      was reduced from 70.1 +/- 4.2 % with control to 41.1 +/- 4.0 % with milks
      containing plant sterol (P < 0.001). CONCLUSIONS: These results demonstrate that
      properly solubilized non-esterified plant sterols in milks significantly inhibit
      cholesterol absorption in mildly hypercholesterolemic men.

PMID- 12811475
TI  - Short-term dietary conjugated linoleic acid supplementation does not enhance the
      recovery of immunodepleted dexamethasone-treated rats.
AB  - BACKGROUND: Conjugated linoleic acid (CLA) has been reported to decrease fat
      deposition, and increase lean body mass. This has been broadly inferred to mean
      that CLA alters protein turnover. However, data to test the effects of CLA on
      protein turnover are lacking. An enhancement in immune responses by CLA has also
      been demonstrated. AIM OF THE STUDY: The objective of this study was to determine
      the potential for dietary CLA and protein intervention to improve nutritional and
      functional recovery in an animal model of catabolic stress and immunodepletion.
      METHODS: Diets varying in their protein levels in the presence or absence of CLA
      were tested for their effects on the recovery of glucocorticoid (intraperitoneal
      injection of dexamethasone, 120 mg/kg) treated rats. Following steroid injection,
      rats were fed 4 dietary treatments for 4 d. The diets contained 10 or 20 g/100 g
      protein with or without 0.5 g/100 g CLA. RESULTS: Dexamethasone treatment
      resulted in a decreased food intake and loss of weight, independent of dietary
      treatment. A higher number of blood monocytes occurred in rats fed the high CLA
      diets. The protein fractional synthesis rate in spleens of rats fed the diets
      containing either high proteins or CLA were higher compared to those fed diets
      with low protein content or without CLA, respectively. CLA, consumed post
      dexamethasone treatment, did not improve protein turnover in the other tissues
      studied, including gut mucosa, liver, muscle and thymus. CONCLUSIONS: The present
      study was performed to determine the effect of CLA in acute conditions, as
      opposed to a preventive approach, on the recovery from a catabolic stress with
      immunodepletion. Overall, no effect of short-term feeding CLA on the recovery
      from dexamethasone-mediated immunodepletion was observed.

PMID- 12811476
TI  - Prognostic significance of Bcl-2 and p53 expression in gastric cancer.
AB  - BACKGROUND AND AIMS: Apoptosis regulates cell death and influences cell
      proliferation and therefore may play an important role in development or growth
      of various malignant tumors. The Bcl-2 and p53 are closely linked in the
      regulation of apoptosis. We investigated the prognostic significance of Bcl-2 and
      p53 expression in patients with gastric cancer. PATIENTS AND METHODS:
      Immunohistochemistry was used to study Bcl-2 and p53 expression in 308
      consecutive patients with gastric cancer. RESULTS: Bcl-2 expression was positive
      in 39 patients (12.7%) and showed a significant negative correlation with depth
      of invasion and lymph node metastasis. p53 expression was observed in 105
      patients (34.1%) and was significantly associated with depth of invasion, lymph
      node metastasis, distant metastasis, and intestinal type. Patients with Bcl-2(+)
      tumors showed a trend to better 5-year survival rate (81%) than those with Bcl-2(
      ) negative tumors (71%). The 5-year survival rate in p53 positive cases (60%) was
      significantly lower than that in p53-negative cases (78%). In addition, p53
      expression showed a significantly poorer prognosis in both diffuse and intestinal
      types. In multivariate analysis restricted to patients with R0 resection p53
      expression was an independent prognostic factor (relative risk: 2.063). In
      combined assessment of p53 and Bcl-2 expression the group with p53(+)/Bcl-2(-)
      tumors showed significantly worse 5-year survival (57%) than the other groups,
      while best survival was seen in the group with p53(+)/Bcl-2(+) tumors (100%).
      CONCLUSION: p53 expression is an unfavorable prognostic factor in gastric cancer.
      Bcl-2 expression may have possible prognostic value when combined with p53
      expression.

PMID- 12811477
TI  - Long segment Hirschsprung's disease in the Waardenburg-Shah syndrome.
AB  - Presentation with signs of bowel obstruction in an infant with Waardenburg
      syndrome should raise the suspicion of aganglionosis. We report such a case of
      long segment Hirschsprung's disease associated with Waardenburg syndrome. Long
      term care of such children is fraught with high morbidity and mortality.

PMID- 12811478
TI  - Fetal surgery for repair of myelomeningocele allows normal development of the
      rectum in sheep.
AB  - To determine whether fetal surgery in a fetus with myelomeningocele (MMC) allows
      normal development of rectal muscles and nerves, we analyzed the rectum after
      fetal surgery in a sheep model. An MMC lesion was surgically created in 13 fetal
      sheep at 75 days of gestation. One fetal sheep died after the lesion was created.
      Eight fetal sheep were repaired at 100 days of gestation; the others were not
      repaired, as a control (n=4). Three methods were used for fetal surgery of MMC:
      standard neurosurgical repair (4 fetal sheep), covering of the MMC lesion by
      Alloderm (2 fetal sheep), and covering of the MMC lesion by Gore-Tex (2 fetal
      sheep). At 140 days of gestation, fetal sheep were harvested and histo
      pathological analysis was performed on the rectum using hematoxylin and eosin
      staining for muscles and S-100 protein staining for nerves. One fetal sheep
      treated by standard neurosurgical repair died before harvesting. The four
      untreated fetal sheep had hypoplastic longitudinal muscles of the rectum but well
      developed-circular muscles. In addition, the untreated fetuses had a hypoplastic
      submucosal nerve plexus but a well-developed intermuscular nerve plexus. In
      contrast, treated fetal sheep had well-developed longitudinal and circular
      muscles except for one sheep treated with standard neurosurgical repair. In
      addition, except for the same fetal sheep, treated fetal sheep had well-developed
      nerve plexuses. There was no difference in muscle and nerve development of the
      rectum among the three repair methods. Fetal surgery for repair of MMC allows
      normal development of rectal muscles and nerves.

PMID- 12811479
TI  - Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal
      smooth muscles in hypoganglionosis: is hypoganglionosis a disorder of the
      neuromuscular junction?
AB  - BACKGROUND: Hypoganglionosis (HP) is characterized histologically by a decreased
      number of ganglion cells in intestinal myenteric plexuses and functionally by
      severely impaired gut motility. The purpose of the present study was to
      investigate the neuromuscular junction (NMJ) in small- and large-intestine biopsy
      specimens from patients with HP. METHODS: Fresh frozen sections of small and
      large intestine from three patients with HP and five age/site-matched controls
      were examined. All specimens were labeled with neural cell adhesion molecule
      (NCAM) antibodies and synaptophysin (SY) antibodies to delineate the NMJ.
      RESULTS: Normal small- and large-intestine specimens had a moderate number of
      NCAM-positive NMJ in association with nerve fibers in the lamina propria,
      muscularis mucosa, and many NCAM-positive NMJ in association with nerve fibers in
      the circular and longitudinal muscle layers. In HP, there was lack of expression
      of NCAM-positive NMJ in association with nerve fibers in the lamina propria,
      muscularis mucosa, and circular and longitudinal muscle layers in both small- and
      large-intestine specimens, and a marked increase in NCAM expression in the
      muscularis mucosa and the inner border of the circular muscle layer that was only
      seen in HP specimens. SY-positive synaptic vesicles were observed throughout the
      gut in all normal specimens, but there was a lack of SY expression in HP
      specimens. Expression of NCAM and SY in ganglion cells was the same in all
      specimens. CONCLUSION: These findings suggest there is a complicated abnormality
      of the NMJ in HP that may prove to contribute to the disturbances in gut motility
      seen in this condition.

PMID- 12811480
TI  - No incidence of port-site recurrence after endosurgical procedure for pediatric
      malignancies.
AB  - Port-site recurrence (PSR) following laparoscopic procedures has been an
      unpredictable complication in adult cancer patients; however, no data exist about
      this phenomenon in the pediatric field. The aim of this study was to determine
      whether PSR, following endosurgical procedure for malignancies, is a typical
      complication or a rare event in the pediatric population. Eighty-one
      questionnaires were mailed to members of The Japanese Society of Pediatric
      Endosurgeons. They were asked to provide a list of their institutions that had
      experience with PSR after endosurgical procedures for pediatric malignancies.
      Among 29 institutions, a total of 129 endosurgical procedures for pediatric
      malignancies were reported; these included 85 laparoscopic and 44 thoracoscopic
      procedures, performed on 104 neuroblastomas, 8 hepatoblastomas, 7
      nephroblastomas, and 10 other tumors. Of the 104 neuroblastomas, 83 were found by
      mass screening using high levels of urinary vanillylmandelic acid and
      homovanillic acid. Sixty-five of the 83 patients had their tumor excised, and 18
      had their tumor biopsied by endosurgical procedures. Additionally, 47 of these
      patients did not require any postoperative chemotherapy. No incidence of PSR was
      reported in any of the patients that underwent endosurgical procedures. The PSR
      following endosurgical procedure is a rare phenomenon in the pediatric
      population. Both, laparoscopic and thoracoscopic procedures, are safe and
      recommended for treating pediatric malignancies, especially mass-screened
      neuroblastomas.

PMID- 12811481
TI  - Recurrent tracheoesophageal fistula after foreign body impaction.
AB  - We describe a case of recurrent tracheoesophageal fistula in a child previously
      operated for esophageal atresia and tracheoesophageal fistula following impaction
      of a foreign body. After extracting the foreign body, the diagnosis of recurrence
      was confirmed by esophagogram and bronchoscopy. The fistula was approached
      through transpleural thoracotomy and repair effected without significant
      difficulty. The possibility of unrecognized foreign body impactions as the
      etiological factor for late recurrence of tracheoesophageal fistula is discussed.

PMID- 12811482
TI  - Laparoscopic gastropexy in a neonate for acute gastric volvulus.
AB  - A 26-day-old male neonate presented with an acute gastric volvulus which was
      reduced with a nasogastric catheter. The patient was then subjected to
      laparoscopic anterior gastropexy. Six months after the procedure, the child is
      thriving and completely free of symptoms. We present this case as the first
      wherein a laparoscopic gastropexy has been done for gastric volvulus in a
      neonate. We have found the procedure acceptable for the treatment of neonates
      with gastric volvulus.

PMID- 12811483
TI  - A case of body stalk anomaly arising in the second baby of a triplet pregnancy
      after in-vitro fertilization and embryo transfer.
AB  - We report a case of body stalk anomaly arising in the second baby of a triplet
      pregnancy after in-vitro fertilization and embryo transfer (IVF-ET). Body stalk
      anomaly or limb-body wall complex is a rare congenital anomaly with a series of
      similar clinical manifestations and poor prognosis. IVF-ET is an effective
      treatment for various types of infertility. We summarize and discuss herein the
      relation with the sequence of genesis for such malformations and multiple
      pregnancies after IVF-ET.

PMID- 12811484
TI  - Antenatal proton MR spectroscopy of the human brain in vivo.
AB  - INTRODUCTION: The assessment of metabolites in the human fetal brain in utero
      could have diagnostic value. We explored the feasibility and potentials of proton
      magnetic resonance spectroscopy ((1)H MRS) for this purpose. RESULTS: (1)H MRS
      was successfully performed in the third trimester of pregnancy without using
      sedation. Signals for inositol, choline, creatine, and N-acetylasparatate (NAA)
      compounds were detected in MR spectra from single voxels in the brain. Absolute
      tissue levels of these metabolites resemble values measured in preterm and term
      babies, especially of relatively more mature brain regions, from which most of
      the MR spectra have been obtained. Brain maturation between 30 and 41 weeks of
      gestation was most clearly reflected by increasing levels of the neuronal marker
      NAA. CONCLUSION: With proper care for the methodological aspects, antenatal (1)H
      MRS clearly has the potential to evolve into a clinical tool for assessing a
      number of key metabolites in the human fetal brain in utero.

PMID- 12811485
TI  - Screening for infectious diseases.
AB  - INTRODUCTION: Fetal brain injury is an essential cause of lifelong morbidity.
      Infection appears as a cause of brain damage. Apart from chorioamnionitis,
      screening for infectious diseases must be considered in pregnancies with a risk
      of congenital infection or cases with abnormal cerebral ultrasound findings.
      DISCUSSION: Congenital infections include most of the major components of the
      TORCH complex: toxoplasmosis, rubella, cytomegalovirus, herpes, and varicella.
      Seronegative mothers can develop primary infection, which carries a risk of
      vertical transmission. The timing of the infection is a critical point, because
      fetal damage often depends on the gestational age at which acute maternal
      infection took place and occurs more likely in the first half of pregnancy.
      Antenatal ultrasound can detect brain abnormalities, like hydrocephalus,
      periventricular leukomalacia, calcifications or hemorrhage. Maternal serologic
      tests must be performed to look for an infectious etiology; the most frequent
      agents are the components of the TORCH complex. But additional serology must
      include parvovirus B19, HIV, and coxsackieviruses.

PMID- 12811486
TI  - Screening for genetic disorders.
AB  - INTRODUCTION: Cerebral malformations can be genetically determined and/or part of
      complex syndromes. When the defect is detected during pregnancy, it important to
      rule out an associated genetic condition. Family history and detailed examination
      of fetal anatomy are needed. DISCUSSION: Intrauterine growth retardation, as well
      as limb abnormalities (especially polydactyly) are strong indicators of a genetic
      condition in the context of a fetal cerebral malformation. A standard chromosomal
      analysis is needed in all cases. Fluorescent in situ hybridization (FISH)
      techniques using locus-specific probes that permit the detection of subtle
      chromosomal rearrangements and metabolic analyses may be indicated when a
      specific condition is suspected. As for molecular analyses, they have so far been
      mainly applicable to pregnancies at risk of a known disorder because of family
      history. The diagnosis consists of determining whether the fetus has inherited
      the causative mutation identified in the index case. When termination of
      pregnancy is elicited, a careful prenatal and postnatal examination is needed in
      order to give accurate genetic counseling for further pregnancies. Storage of
      fetal material allowing further molecular analyses is strongly recommended.

PMID- 12811487
TI  - Dietary protein reduction in sheep and goats: different effects on L-alanine and
      L-leucine transport across the brush-border membrane of jejunal enterocytes.
AB  - It was the aim of this study to examine the potential regulatory effects of a
      long-term low dietary protein supply on the transport capacity of the jejunal
      brush-border membrane for amino acids. For this purpose, we used the neutral
      amino acids L-alanine (representative for nonessential amino acids) and L-leucine
      (representative for essential amino acids) as model substances. Ten sheep lambs,
      8 weeks of age and 19-27 kg body weight, were allotted to two dietary regimes
      with either adequate or reduced protein supply which was achieved by 17.9% and
      9.7% of crude protein in the concentrated feed, respectively. The feeding periods
      were 4-6 weeks in length. Similarly, eight goat kids of 5-7 weeks of age and 8-14
      kg body weight were allotted to either adequate (crude protein 20.1%, feeding
      period 9-12 weeks) or reduced protein supply (10.1%, feeding period 17-18 weeks).
      Dietary protein reduction in lambs caused a significant body weight loss of 0.6
      +/- 0.7 kg, whereas the body weight in control animals increased by 1.9 +/- 0.7
      kg (P<0.05). Plasma urea concentrations decreased significantly by 60% (low
      protein 2.3 +/- 0.1 versus control 5.7 +/- 0.2 mmol l(-1), P<0.001). In kids,
      reduction of dietary protein intake led to significant decreases of the daily
      weight gain by 48% from 181 +/- 8 g to 94 +/- 3 g (P<0.001) and daily dry matter
      intake by 27% from 568 +/- 13 g to 417 +/- 6 g (P<0.01). Respective urea
      concentrations in plasma were reduced by 77% from 5.2 +/- 0.4 to 1.2 +/- 0.2 mmol
      l(-1) (P<0.01). Kinetic analyses of the initial rates of alanine uptake into
      isolated jejunal brush-border membrane vesicles from sheep and goats as affected
      by low dietary protein supply yielded that the apparent Km was neither
      significantly different between the species nor significantly affected by the
      feeding regime thus ranging between 0.12 and 0.16 mmol.l(-1). Reduction of
      dietary protein, however, resulted in significantly decreased Vmax values of the
      transport system by 25-30%, irrespective of the species. Kinetic analyses of the
      initial rates of leucine uptake into jejunal brush-border membrane vesicles from
      sheep and goats yielded that leucine uptake was mediated by Na+-dependent as well
      as Na+-independent processes. Similar to alanine, apparent Km values of leucine
      uptake were neither different between the species nor affected due to low dietary
      protein and ranged between 0.08 and 0.15 mmol l(-1). In contrast to the alanine
      transport mechanism, dietary protein reduction resulted in increased Vmax values
      of Na+-dependent leucine transport by 53% in sheep and 230% in goats. Similarly,
      Na+-independent leucine uptake was stimulated by 85% and 200% in sheep and in
      goats, respectively. This study shows adaptation of amino acid absorption at the
      brush-border membrane level of jejunal enterocytes of small ruminants due to
      dietary protein reduction. Whereas the transport capacity for the nonessential
      amino acid alanine was reduced due to low dietary protein, the transport capacity
      for the essential amino acid leucine was markedly stimulated. From this, the
      involvement of rather different feedback mechanisms in adaptation of intestinal
      amino acid transport mechanisms has to be discussed.

PMID- 12811488
TI  - Regulation of ipsilateral visual information within the tectofugal visual system
      in zebra finches.
AB  - The eyes of zebra finches are placed laterally, the foveae are looking into
      different directions. It is unlikely that the birds are able to process different
      images from both eyes simultaneously. A neural mechanism might therefore be
      necessary to guide the birds' attention to one of the two eyes and to reduce the
      processing of information of the other. Previous studies revealed that
      information from the ipsilateral eye is indeed suppressed on its way to the
      telencephalon by the activity of the contralateral eye. It has been suggested
      that two nuclei of the tecto-thalamic tract, nucleus subpraetectalis and nucleus
      interstitio praetecto subpraetectalis, are a central part of such a suppressive
      mechanism. Using electrophysiological recordings, we investigated the influence
      of these two nuclei and nucleus rotundus on the processing of binocular visual
      information by treating the nuclei with picrotoxin or electrolytic lesions.
      Deactivation of inhibitory neurons within SP/IPS leads to a significant increase
      of the ectostriatal responses to ipsilateral and bilateral stimulation, the
      responses to contralateral stimulation remain unaffected. Lesioning SP/IPS does
      not alter the responses to visual stimuli. Treatment of nucleus rotundus with
      picrotoxin increases contralaterally and bilaterally, but not ipsilaterally
      evoked responses. A wiring diagram is presented which interprets these findings.

PMID- 12811489
TI  - Electrophysiological recordings during the peripheral nerve evaluation (PNE) test
      in complete spinal cord injury patients.
AB  - Up until now, the exact mechanism by which neuromodulation using sacral nerve
      stimulation works still remains unknown. Recent studies of pelvic floor
      contraction during peripheral nerve evaluation (PNE) have shown that several
      muscle responses are reflexly mediated. However, whether these reflexes originate
      from a segmental level within the sacral spinal cord or from supraspinal neuronal
      centers involving spino-bulbospinal pathways remains to be determined. Therefore,
      recordings of external anal sphincter reflexes during PNE in complete spinal cord
      injury (SCI) patients was performed. Three patients with complete SCI (two female
      and one male) suffering from neurogenic incontinence underwent the first stage of
      a stimulator implant (peripheral nerve evaluation). Stimulation was obtained
      through an electrode placed in the S3 foramen. Concomitantly, the latency of the
      response of the striated anal sphincter was measured using a concentric needle
      electrode placed in the striated part of the anal sphincter. Repeated
      measurements within an interval of 30 min were performed to confirm the
      reliability of the responses. In all subjects, reflex responses of early and late
      latencies could be recorded. The early response showed a mean latency of 41.2 ms
      (range 33.3-62 ms), which corresponds to a segmental reflex, similar to the
      pudendo-anal reflex. The late response appeared with a mean latency of 189.4 ms
      (range: 183.3-197.8 ms) and with high variability and fatigability, suggesting a
      reflex response organized at polysegmental spinal levels. Despite successful
      foramina lead placement, none of our complete SCI patients showed any improvement
      of neurogenic incontinence after 5 days of treatment by sacral nerve stimulation.
      The findings confirm that the anal contractions observed during peripheral nerve
      evaluation are reflex responses mediated by afferent pathways. Both the early and
      late reflex responses are of spinal origin, since they were obtained in complete
      SCI patients in whom all spino-bulbo spinal loops are supposed to be interrupted.
      The finding that neuromodulation is working in non-neurogenic patients but is
      less successful in complete SCI patients could give evidence that preserved spino
      bulbo spinal loops contribute to the positive effects of neuromodulation. The
      role of an eventual spino-bulbo spinal loop acting during neuromodulation in non
      neurogenic patients has to be assessed in further studies.

PMID- 12811490
TI  - Oxytocin plasma levels in the systemic and cavernous blood of healthy males
      during different penile conditions.
AB  - It is well established that transmitters of the nonadrenergic-noncholinergic
      (NANC) system are involved in the control of sexual arousal and penile erection
      in healthy males. The proerectile activity of dopamine D1/D2 receptor agonist
      apomorphine-HCl (IXENSE, UPRIMA) involves oxytocinergic pathways descending from
      the hypothalamus to the brain stem and spinal autonomic centers. Although it has
      been demonstrated that injection of oxytocin into the paraventricular nucleus and
      the hippocampus produces penile erection in rats, the significance of the peptide
      in the control of sexual arousal and penile erection in man has been, up until
      now, only poorly evaluated. The present study was undertaken to determine whether
      oxytocin (OT) plasma levels alter in the systemic and cavernous blood of healthy
      males under different penile conditions (flaccidity, tumescence, rigidity,
      detumescence). Twenty-five healthy adult males were exposed to visual and tactile
      erotic stimuli in order to elicit penile tumescence and rigid erection. Blood was
      taken from the corpus cavernosum (CC) and the cubital vein (CV) during penile
      flaccidity, tumescence, rigidity and detumescence. Following extraction from
      plasma aliqouts, oxytocin was measured by means of a radioimmunoassay. An
      increase was observed in the mean OT plasma levels in the systemic and cavernous
      blood when the flaccid penis became tumescent (CC: from 66.7+/-34 to 75+/-44
      pg/ml; CV: from 71+/-41 to 79+/-49.5 pg/ml). From tumescence to rigidity, OT
      further rose in the cavernous blood (to 81+/-58 pg/ml), whereas it remained
      unaltered in the systemic circulation. During detumescence, oxytocin plasma
      levels dropped in the cavernous but again increased in the systemic blood (to
      94+/-49 pg/ml). Our results support the hypothesis of a pivotal role of OT in the
      mechanism of male sexual arousal and penile erection and provide a rationale for
      the use of apomorphine in the treatment of erectile dysfunction.

PMID- 12811491
TI  - Prevalence and burden of overactive bladder in the United States.
AB  - CONTEXT: the National Overactive BLadder Evaluation (NOBLE) Program was initiated
      to better understand the prevalence and burden of overactive bladder in a broad
      spectrum of the United States population. OBJECTIVE: to estimate the prevalence
      of overactive bladder with and without urge incontinence in the US, assess
      variation in prevalence by sex and other factors, and measure individual burden.
      DESIGN: US national telephone survey using a clinically validated interview and a
      follow-up nested study comparing overactive bladder cases to sex- and age-matched
      controls. SETTING: noninstitutionalized US adult population. PARTICIPANTS: a
      sample of 5,204 adults >/=18 years of age and representative of the US population
      by sex, age, and geographical region. MAIN OUTCOME MEASURES: prevalence of
      overactive bladder with and without urge incontinence and risk factors for
      overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and
      MOS sleep scores were used to assess impact. RESULTS: the overall prevalence of
      overactive bladder was similar between men (16.0%) and women (16.9%), but sex
      specific prevalence differed substantially by severity of symptoms. In women,
      prevalence of urge incontinence increased with age from 2.0% to 19% with a marked
      increase after 44 years of age, and in men, increased with age from 0.3% to 8.9%
      with a marked increase after 64 years of age. Across all age groups, overactive
      bladder without urge incontinence was more common in men than in women.
      Overactive bladder with and without urge incontinence was associated with
      clinically and significantly lower SF-36 quality-of-life scores, higher CES-D
      depression scores, and poorer quality of sleep than matched controls.
      CONCLUSIONS: the NOBLE studies do not support the commonly held notion that women
      are considerably more likely than men to have urgency-related bladder control
      problems. The overall prevalence of overactive bladder does not differ by sex;
      however, the severity and nature of symptom expression does differ. Sex-specific
      anatomic differences may increase the probability that overactive bladder is
      expressed as urge incontinence among women compared with men. Nonetheless,
      overactive bladder, with and without incontinence, has a clinically significant
      impact on quality-of-life, quality-of-sleep, and mental health, in both men and
      women.

PMID- 12811492
TI  - Strategies to promote recovery of cavernous nerve function after radical
      prostatectomy.
AB  - While the application of penile autonomic nerve-sparing techniques during radical
      prostatectomy for clinically localized prostate cancer has improved erection
      recovery rates after surgery, many men still experience delayed or incomplete
      recovery of erectile function. In recognition of neuropathy as a likely basis for
      erectile dysfunction after radical prostatectomy, investigators have begun
      exploring new strategies to promote the functional recovery of nerves responsible
      for penile erection in the course of this management. Primary efforts continue
      for preserving the integrity of the penile nerves, while the next frontier in
      clinical management has encompassed strategies directed toward maximally
      restoring their function. Such strategies include cavernous nerve interposition
      grafting and neurotrophic treatments that meet nerve reconstructive and nerve
      regenerative objectives, respectively. Early successes with both innovations
      preclinically and clinically suggest their feasibility and potential roles to
      reduce the incidence of erectile dysfunction after radical prostatectomy. The
      purpose of this report is to review strategies under development to promote post
      prostatectomy erectile function, particularly with respect to preserving penile
      innervation involved in this function.

PMID- 12811493
TI  - Laparoscopic evaluation of testicular mobility as a guide to management of intra
      abdominal testes.
AB  - The optimal management of intra-abdominal testes is the subject of an ongoing
      debate as the result of widespread use of laparoscopy since early 1990's. A
      simple laparoscopic technique uses cord mobility to act as a guide to cord length
      and therefore predict the success of a conventional orchidopexy in cases of true
      intra-abdominal testes. In the technique described, the testis is displaced by
      stretching the testes to overly the opposite internal inguinal ring. Over a 3
      year period, a total of 36 boys with 38 intra-abdominal testes, confirmed
      laparoscopically, were prospectively assessed. The reported "stretching maneuver"
      was carried out in all cases. Successful conventional orchidopexy as predicted by
      a positive stretch maneuver was carried out in 20 testes. When the stretch
      maneuver failed, conventional 2-stage open operation was done in 3 patients and
      Fowler-Stephens orchidopexies for the remaining 13 children. A simple test
      determining testicular mobility assessed during laparoscopic evaluation of intra
      abdominal testes provides information of significant importance upon which the
      correct surgical approach can be based.

PMID- 12811494
TI  - The role of the carbachol test and concomitant diseases in patients with
      nonobstructive urinary retention undergoing sacral neuromodulation.
AB  - The aim of this study was to evaluate the percutaneous nerve evaluation (PNE)
      test success in patients with nonobstructive urinary retention. A total of 24 PNE
      tests were performed in patients with nonobstructive urinary retention and in 18
      patients, a carbachol test was performed during urodynamics. The diagnosis
      relating to the acontractile detrusor was also assessed and compared to the
      outcome of the PNE test. The PNE test was successful in eight of 24 patients
      (33.3%) with the the highest success rate being observed in patients after
      hysterectomy (80%). It was successful in five of 12 patients with negative
      carbachol tests and in three of six patients with positive carbachol tests. We
      conclude that sacral neuromodulation is an effective treatment option in patients
      with nonobstructive urinary retention. PNE tests should be performed in all
      patients with therapy resistant nonobstructive urinary retention, because
      predictive factors do not exist.

PMID- 12811495
TI  - Treatment of penile curvature--how to combine the advantages of simple plication
      and the Nesbit-procedure by superficial excision of the tunica albuginea.
AB  - Different treatment options for penile curvature exist, such as the Nesbit
      procedure with complete excision of the tunica albuginea or the simple plication.
      We prefer a modification with only superficial excision, not opening the corpora
      cavernosa. From January 1997 to June 2000, 68 patients were treated surgically
      due to penile curvature. Data was obtained from 48 patients by telephone
      interview. The mean penile deviation was 46 degrees. Excision of the tunica was
      performed only superficially and non-absorbable inverted sutures were used. The
      mean follow-up time in this study was 25 months. A total of 36 (75%) patients
      were satisfied postoperatively, 12 were unsatisfied. Eleven (23%) patients
      described a complete straightening, 37 (77%) a rest-curvature of 5-50 degrees
      (mean 14 degrees ) and 21 (44%) described a shortening of 0.5-5 cm (mean 1.2 cm).
      Six patients reported a recurrence. No new erectile dysfunction occurred.
      Superficial excision of the tunica albuginea offers the advantage of tissue
      contraction due to scarring without destroying the integrity of the corpora,
      leading in combination with non-absorbable inverted sutures to good functional
      and cosmetic results.

PMID- 12811496
TI  - Minimal incision living donor nephrectomy compared to the hand-assisted
      laparoscopic living donor nephrectomy.
AB  - BACKGROUND: There has been a surge of minimally invasive procedures for living
      donor nephrectomy. We compared our minimal incision living donor (MILD)
      nephrectomy to hand-assisted laparoscopic (HAL) living donor nephrectomy METHODS:
      We conducted a Medline search and compared our first 45 MILD nephrectomies to the
      data from the University of Michigan (UM), Tulane University (TU), and the
      University of Chicago (UC). RESULTS: The MILD incision was smaller than the
      cumulative incisions in the UM and UC groups (8.6, 11 and 10.4 cm, respectively).
      The operating times were similar in the UM and UC groups (209, 246, and 215 min,
      respectively). The UM and TU lengths of hospital stay (1.8 and 2.2 days) were
      shorter than those of the MILD and UC groups (2.5 and 2.8 days). CONCLUSIONS:
      MILD nephrectomy has results similar to those of HAL living donor nephrectomy. It
      allows the surgeon with a traditionally trained background to perform a safe,
      minimally invasive operation without laparoscopic technology.

PMID- 12811497
TI  - Franz von Paula Gruithuisen (1774-1852): lithotrity pioneer and astronomer. On
      the 150th anniversary of his death.
AB  - On the occasion of the 150th anniversary of the death of Franz von Paula
      Gruithuisen, the authors present his life and work. His most significant work in
      the fields of urology and lithotrity is examined, with special emphasis on the
      development of the latter field. He published his epoch-making historic study in
      1813 in the Journal of Medicine and Surgery (Medicinisch-Chirurgische Zeitung).
      Franz von Paula Gruithuisen, the Bavarian physician and astronomer, led the way
      in the field of lithotrity. He developed crucial ideas on how to remove bladder
      stones transurethrally in a way that was safer and less likely to cause death.
      His instruments can be regarded as the model on which subsequent devices are
      based. Gruithuisen's influence on European medical scientists and, in particular,
      his rivalry with Jean Civiale are discussed.

PMID- 12811498
TI  - Ultrastructure of the urethra of the Mongolian gerbil.
AB  - OBJECTIVE: The urethra is the main port of entry of sexually transmitted
      pathogens. However, papers on the morphology of the urethra are scarce. The
      Mongolian gerbil is a rodent native of the Mongolia and China and has been
      utilized as a laboratory animal since the 1960s. This work describes the
      ultrastructure of the urethra of the Mongolian gerbil to provide data for future
      experimental studies. METHODS: The urethra of ten adult male gerbils was studied
      by transmission electron microscopy. RESULTS: The epithelium of the pelvic
      urethra possesses two cell types: I and II, without the formation of cellular
      layers, while the penile urethra possesses cellular layers: basal, intermediate
      and superficial. The urethra presents neurosecretory cells belonging to the amine
      precursor uptake and decarboxylation system. CONCLUSIONS: The urethral epithelium
      of the gerbil is a neurosecretory epithelium, part of the amine precursor uptake
      and decarboxylation system.

PMID- 12811499
TI  - Glutathione S-transferase isoenzyme profile in non-tumor and tumor human kidney
      tissue.
AB  - Glutathione S-transferase (GST) isoenzyme profiles of non-tumor and tumor renal
      tissue of patients suffering from renal cell carcinoma (RCC) of the clear cell
      type were determined and compared to those of normal renal tissue. GST
      isoenzyme(s) were first separated on the basis of their affinity to glutathione
      sepharose 4B affinity column. Affinity-bound GSTs were further purified by
      anionic and cationic chromatofocusing. The results presented in this study show
      that non-tumor tissue distant from renal tumors and renal tumors have lower
      specific GST activity and a different isoenzyme profile than normal human kidney.
      Purification of normal kidney GSTs by affinity chromatography revealed the
      presence of two GST fractions: flow-through GST without affinity for glutathione
      affinity resin and GST fraction tightly bound to affinity matrix. In non-tumor
      kidney tissue of RCC patients, substantially less flow-through GST fraction was
      found, whereas renal tumors did not express flow-through GST at all. Isoelectric
      chromatofocusing indicated smaller numbers of GST isoenzymes in non-tumor and
      tumor kidney regions, with anionic forms dominating. It could be speculated that
      decreased expression of cationic GST isoenzymes (corresponding to class alpha) in
      non-tumor kidney tissue of RCC patients might be responsible for differences in
      sensitivity to specific carcinogens. The observations that RCCs are devoid of
      affinity flow-through GST and have small number of isoenzymes are further proof
      of low-level GST expression in RCC.

PMID- 12811500
TI  - Controlled, double-blind, multicentre clinical trial to investigate long-term
      tolerability and efficacy of trospium chloride in patients with detrusor
      instability.
AB  - Our objectives were to ascertain the tolerability and efficacy of trospium
      chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in
      patients with urge syndrome. The trial comprised a total of 358 patients with
      urge syndrome or urge incontinence. After randomisation in the ratio of 3:1,
      participants were treated continuously for 52 weeks with either trospium chloride
      (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks,
      patients were physically examined with measurements of blood pressure and pulse
      rate, were questioned about any adverse events, checked for compliance and
      underwent relevant laboratory tests. As an additional safety measure, an ECG was
      made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning,
      and at 26 and 52 weeks to determine the maximal cystometric bladder capacity.
      Among others things, the frequencies of micturition, incontinence and number of
      urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52.
      The evaluation of vital parameters, laboratory results and ECGs did not show any
      relevant changes attributable to the action of the anticholinergics. Analysis of
      the micturition diary clearly indicated a reduction of the micturition frequency,
      incontinence frequency, and a reduction of the number of urgencies in both
      treatment groups. Mean maximum cystometric bladder capacity increased during
      treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52
      weeks (P=0.001). Further comparison with oxybutynin did not reveal any
      statistically significant differences in urodynamic variables between the drugs.
      Adverse events occurred in 64.8% of the patients treated with trospium chloride
      and 76.7% of those treated with oxybutynin. The main symptom encountered in both
      treatment group was dryness of the mouth. For patients on trospium chloride, the
      estimated risk of an unexpected adverse event was 0.027 per patient per week for
      all adverse events and 0.009 for dryness of the mouth, resulting in a
      considerably lower risk during treatment given with trospium chloride than with
      oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the
      drugs reveals a comparable efficacy level and a better benefit-risk ratio for
      trospium chloride than for oxybutynin due to better tolerability.

PMID- 12811501
TI  - Endoluminal treatment of aortic dissection.
AB  - Aortic dissection is most often a catastrophic medical emergency which, if
      untreated, can be potentially fatal. The intention of therapy in patients with
      aortic dissection is to prevent aortic rupture or aneurysm formation as well as
      to relieve branch vessel ischaemia. Patients with aortic dissection are often
      poor candidates for anaesthesia and surgery and the surgical procedure itself is
      challenging requiring thoracotomy, aortic cross clamping, blood transfusion as
      well as prolonged hospital stay in some cases. Operative mortality is especially
      high in patients with critical mesenteric or renal ischaemia. The past decade has
      experienced the emergence of a number of interventional radiological or minimally
      invasive techniques which have significantly improved the management of patients
      with aortic dissection. These include stent grafting for entry site closure to
      prevent aneurysmatic widening of the false lumen as well as percutaneous
      techniques such as balloon fenestration of the intimal flap and aortic true lumen
      stenting to alleviate branch vessel ischaemia. False lumen thrombosis following
      entry closure with stent grafts has been observed in 86-100% of patients, whereas
      percutaneous interventions are able to effectively relieve organ ischaemia in
      approximately 90% of the cases. In the years to come, it is to be expected that
      these endoluminal techniques will become the method of choice for treating most
      type-B dissections and will assist in significantly reducing the number of open
      surgical procedures required for type-A dissections. The intention of this
      article is to provide an overview of the current status of these endoluminal
      techniques based on our own experience as well as on a review of the relevant
      literature.

PMID- 12811502
TI  - Sarcoidosis: assessment of disease severity using HRCT.
AB  - The value of high-resolution computed tomography (HRCT) in diagnosing and
      assessing inflammatory activity in sarcoidosis is well established. The aim of
      the present study was to address the intra- and inter-observer agreements of the
      HRCT score by Oberstein et al. [8], and to evaluate the relationship between HRCT
      findings and disease severity expressed in respiratory functional impairment in
      sarcoidosis. The clinical records of 80 known sarcoidosis patients visiting the
      outpatient clinic between January 2000 and August 2001, who underwent a HRCT as
      well as lung function tests (including exercise testing), were reviewed. Two
      readers scored the first 60 HRCT images twice. Weighted kappa and intra-class
      correlation coefficient were used to assess the reliability of the HRCT scoring
      system. Spearman's rank correlation coefficients and multiple regression analyses
      were performed to evaluate the relationship between HRCT findings (first reading,
      reader A) and respiratory functional impairment. Intra- and inter-reader
      reliability demonstrated good agreement. All HRCT subscores, except enlargement
      of lymph nodes, were correlated to the FEV(1), FVC, DLco, Pao(2)max (all p<0.05)
      and A-aPo(2 )max ( p<0.001). Furthermore, HRCT abnormalities, but not the chest
      radiographic stage, were strongly associated with functional parameters. Abnormal
      changes of lung parenchyma, established by HRCT features, were associated with
      respiratory functional impairment in sarcoidosis. Moreover, compared with the
      radiographic stages, HRCT findings appeared to be much more sensitive in
      depicting respiratory disability, especially abnormal gas exchange.

PMID- 12811503
TI  - Evaluation of changes in central airway dimensions, lung area and mean lung
      density at paired inspiratory/expiratory high-resolution computed tomography.
AB  - The aim of this study was to improve the understanding of interdependencies of
      dynamic changes in central airway dimensions, lung area and lung density on HRCT.
      The HRCT scans of 156 patients obtained at full inspiratory and expiratory
      position were evaluated retrospectively. Patients were divided into four groups
      according to lung function tests: normal subjects ( n=47); obstructive ( n=74);
      restrictive ( n=19); or mixed ventilatory impairment ( n=16). Mean lung density
      (MLD) was correlated with cross-sectional area of the lung (CSA(L)), cross
      sectional area of the trachea (CSA(T)) and diameter of main-stem bronchi (D(B)).
      The CSA(L) was correlated with CSA(T) and D(B). MLD correlated with CSA(L) in
      normal subjects ( r=-0.66, p<0.0001) and patients with obstructive ( r=-0.62,
      p<0.0001), restrictive ( r=-0.83, p<0.0001) and mixed ventilatory impairment ( r=
      0.86, p<0.0001). The MLD correlated with CSA(T) in the control group ( r=-0.50,
      p<0.0001) and in patients with obstructive lung impairment ( r-0.27, p<0.05). In
      patients with normal lung function a correlation between MLD and D(B) was found (
      r=-0.52, p<0.0001). CSA(L) and CSA(T) correlated in the control group ( r=0.67,
      p<0.0001) and in patients with obstructive lung disease ( r=0.51, p<0.0001). The
      CSA(L) and D(B) correlated in the control group ( r=0.42, p<0.0001) and in
      patients with obstructive lung disease ( r=0.24, p<0.05). Correlations for
      patients with restrictive and mixed lung disease were constantly lower.
      Dependencies between central and peripheral airway dimensions and lung parenchyma
      are demonstrated by HRCT. Best correlations are observed in normal subjects and
      patients with obstructive lung disease. Based on these findings we postulate that
      the dependencies are the result of air-flow and pressure patterns.

PMID- 12811504
TI  - A simple method for enhancing paclitaxel release from Taxus canadensis cell
      suspension cultures utilizing cell wall digesting enzymes.
AB  - Paclitaxel storage in Taxus suspension cell cultures was studied through the
      simple use of cell wall digesting enzymes. The application of cellulase (1%) and
      pectolyase (0.1%) to Taxus canadensis suspension cultures induced a significant
      increase in the paclitaxel present in the extracellular medium while maintaining
      membrane integrity, suggesting that paclitaxel is stored in the cell wall. The
      addition of cell wall digesting enzymes to a cell culture bioprocess may be an
      effective way of enhancing paclitaxel release to the extracellular medium and
      hence simplify product recovery.

PMID- 12811505
TI  - Human leukocyte antigen distribution in Israeli patients with psoriatic
      arthritis.
AB  - OBJECTIVES: This study was designed to investigate the distribution of human
      leukocyte antigen (HLA) classes I and II in a group of Israeli Jewish patients
      with psoriatic arthritis (PsA) and identify HLA markers related to disease
      manifestation in PsA. PATIENTS AND METHODS: Human leukocyte antigens class I and
      class II (both serologically and from oligotyping) were tested in a group of 50
      consecutive patients with PsA, 32 with skin psoriasis (PSO), and 255 healthy
      persons. Data on age, gender, disease duration, and pattern of rheumatological
      manifestations-oligoarthritis, polyarthritis, spinal involvement, involvement of
      distal interphalangeal joints (DIPs), and enthesitis-were registered. RESULTS:
      Human leukocyte antigens A3, B13, and B38 alleles were found to be significantly
      prevalent in PsA compared with PSO patients and healthy controls. HLA-B27 was
      found in only two out of 50 patients with PsA. Patients with PSO and PsA had
      significantly increased incidence of HLA-DRB0101 and -DRB0301, while the
      frequency of HLA-DRB0403 was significantly higher among patients with PsA of
      Ashkenazi origin. We found a statistically significant association between DIP
      involvement and the presence of HLA-A26 and -B38, while HLA-DRB0301 was related
      to spinal involvement. CONCLUSIONS: Psoriatic arthritis in Israeli patients seems
      to be associated with the presence of HLA-A3, -B13, -B38, -DRB0101, and -DRB0301.
      HLA-B27 was not a marker of PsA in this cohort of patients, including patients
      with psoriatic spondyloarthropathy.

PMID- 12811506
TI  - Generation of three-dimensional pannus-like tissues in vitro from single cell
      suspensions of synovial fluid cells from arthritis patients.
AB  - Using single cell suspensions from synovial fluid cells of arthritis patients, we
      observed differentiation of three-dimensional tissues in vitro. This new model of
      pannus-like tissue (PLT) might be useful to study pannus tissue formation and
      differentiation. In the PLT cultures, we observed two cell types, fibroblast-like
      and macrophage-like cells, defined by their distinct morphology and major
      histocompatibility complex (MHC) by human leukocyte antigen (HLA) class II
      expression. We could discriminate several intermediate steps of differentiation
      which finally led to 3D villi-like structures. Secretion of interferon gamma,
      interleukin-10, and tumor necrosis factor alpha was measured in the culture
      supernatants. Using methotrexate at various concentrations, the growth of PLT
      could be inhibited. We describe definite intermediate steps of differentiation.
      The present approach could be a suitable model for the in vitro study of pannus
      tissue formation.

PMID- 12811507
TI  - Serum nitric oxide, catalase, superoxide dismutase, and malondialdehyde status in
      patients with ankylosing spondylitis.
AB  - In this study, serum antioxidant and oxygen derived free radical status of
      patients with ankylosing spondylitis (AS) was investigated and compared with that
      of age- and sex-matched healthy controls. The relationship of these parameters to
      disease activity indices was also examined. Thirty patients with AS not currently
      under disease-modifying antirheumatic drug (DMARD) treatment (e.g., sulfasalazine
      or methotrexate) (15 active and 15 inactive) and 16 age- and sex-matched healthy
      controls were included in the study. Catalase (EC 1.11.1.6), total (Cu-Zn and Mn)
      superoxide dismutase (SOD) (EC 1.15.1.1) activities, and malondialdehyde (MDA),
      nitrite (NO(2)(-)), and nitrate (NO(3)(-)) levels as indices of nitric oxide (NO)
      production were evaluated using appropriate methods. There was no statistically
      significant difference found in SOD activity or NO and MDA levels between active
      and inactive patients. Inactive patients showed no significant difference in all
      the measured oxidant/antioxidant parameters when compared to healthy controls.
      Active patients had significantly higher levels of MDA and catalase enzyme
      activity ( P=0.002 and P=0.007, respectively). There was no significant
      correlation between oxidant/antioxidant parameters and disease activity, C
      reactive protein, erythrocyte sedimentation rate, or Bath Ankylosing Spondylitis
      Disease Activity Index (CRP, ESR, or BASDAI) in either group, except catalase
      enzyme activity, which had a significant correlation with CRP and ESR levels in
      active patients ( r=0.69 and P=0.004, r=0.52 and P=0.04, respectively). Our
      results indicate that oxidative stress and lipid peroxidation are accelerated in
      untreated patients with active AS. Serum catalase activity may be closely related
      to disease activity. In this regard, we underscore the likely benefit of some
      therapeutic interventions including high-potential antioxidants that will
      potentiate the antioxidant defense mechanism and reduce peroxidation in the
      management of AS.

PMID- 12811508
TI  - Autoimmune reaction to type II collagen and cartilage degeneration in MRL/Mp-
      lpr/lpr mouse.
AB  - The early phase of cartilage degeneration was immunohistochemically examined in
      order to clarify the importance of autoimmune reaction against type II collagen
      in MRL/Mp- lpr/lpr (MRL/ l) mouse in an experimental model of rheumatoid
      arthritis (RA). Anti-type II collagen antibodies were detectable in 3-week-old
      mice and preceded the appearance of rheumatoid factors. Furthermore, mesenchymal
      cells and tartrate-resistant acid phosphatase-positive cells began to accumulate
      remarkably in the periphysis, a fibrochondro-osseous area in the bone marrow
      vicinity. The numbers of these cells increased with mice age, together with serum
      levels of anti-type II collagen antibodies. Immunostaining of the periphysis
      revealed expression of type II collagen, IgG, C3, Mac-3, MHC class II antigen Ia,
      and cathepsin-L. Osteoclast-like cells and macrophage infiltration into the
      lesion area were confirmed by transmission electron microscopy. The results
      indicate that cartilage degeneration in MRL/ l mouse may originate in the
      periphysis and progress via a pathway independent of synovial invasion.

PMID- 12811509
TI  - Brucellosis of the spine: evaluation of the clinical, laboratory, and
      radiological findings of 14 patients.
AB  - In this study, we aimed to assess the clinical, laboratory and radiological
      findings of vertebral involvement in brucellosis. Fourteen patients diagnosed
      with spondylitis and spondylodiscitis due to brucellosis were included in the
      study. Computed tomography, magnetic resonance imaging, or scintigraphy were used
      to diagnose the vertebral involvement. The control group consisted of 20 patients
      with brucellosis but no vertebral involvement. The clinical, laboratory, and
      radiological findings of both groups were compared. The prevalence of vertebra
      involvement in brucellosis was found to be 7.5%. Of the 14 study patients, two
      had thoracic, ten had lumbar, and two had both lumbar and sacral vertebral
      involvement. The associated pathologies were spondylodiscitis, narrowing in the
      intervertebral space, inflammation or abscess formation in the paravertebral soft
      tissue, and osteophyte formation. None of the patients had a collapsed vertebral
      body, angulation deformity, or inflammation in the epidural space. In conclusion,
      the possibility of vertebral involvement should be remembered in chronic
      brucellosis, particularly in elderly patients who present with back pain or
      tenderness over the spine. A high index of suspicion and clinical, laboratory,
      and radiological examinations help confirm the diagnosis of vertebral
      involvement.

PMID- 12811510
TI  - Maize BMS cultured cell lines survive with massive plastid gene loss.
AB  - As part of developing an ex planta model system for the study of maize plastid
      and mitochondrial gene expression, a series of established Black Mexican Sweet
      (BMS) suspension cell lines was characterized. Although the initial assumption
      was that their organelle biochemistry would be similar enough to normal in planta
      cells to facilitate future work, each of the three lines was found to have
      plastid DNA (ptDNA) differing from control maize plants, in one case lacking as
      much as 70% of the genome. The other two BMS lines possessed either near-wild
      type ptDNA or displayed an intermediate state of gene loss, suggesting that these
      clonal lines are rapidly evolving. Gene expression profiles of BMS cells varied
      dramatically from those in maize leaf chloroplasts, but resembled those of albino
      plants lacking plastid ribosomes. In spite of lacking most plastid gene
      expression and apparently mature rRNAs, BMS cells appear to import proteins from
      the cytoplasm in a normal manner. The regions retained in BMS ptDNAs point to a
      set of tRNA genes universally preserved among even highly reduced plastid
      genomes, whereas the other preserved regions may illuminate which plastid genes
      are truly indispensable for plant cell survival.

PMID- 12811511
TI  - Sensitization of human breast cancer cells to gemcitabine by the protein kinase C
      modulator bryostatin 1.
AB  - PURPOSE: Protein kinase C (PKC) plays an important role in cell proliferation,
      differentiation, and apoptosis. The interaction between the PKC modulator
      bryostatin 1 (BRYO), and gemcitabine in human breast cancer MCF-7 and MDA-MB-231
      cells and in the non-transformed MCF-10A human breast epithelial cells was
      investigated. METHODS: Immunoblotting was used to determine the expression of PKC
      isoenzymes and proteins involved in the cell cycle and apoptosis. MTT, ELISA and
      flow cytometry assays were used to determine cell survival. RESULTS: Treatment of
      cells with BRYO 200 n M resulted in a significant downregulation of cytoplasmic
      PKC in all three cell lines. However, the expression of membranous PKC was
      differentially affected in these cells. BRYO (1-200 n M) had no significant
      effects on cell viability in any of the cell lines. Nevertheless, BRYO
      significantly enhanced the antiproliferative and apoptotic effects of gemcitabine
      in the MCF-7 and MDA-MB-231 cells, but not in the MCF-10A cells. This was
      associated with significant reduction in the bcl-2/bax ratio. There was a
      significant upregulation of p53, p21(waf1), and p27 in MCF7 and MCF-10A cells
      treated with the combination of gemcitabine and BRYO compared to gemcitabine
      treated cells. CONCLUSIONS: The potentiation of the effect of gemcitabine by BRYO
      was demonstrated in MCF-7 and MDA-MB-231 cells and was associated with a specific
      pattern of PKC modulation. Further investigation of the role of specific isoforms
      of PKC in the downstream molecular events of gemcitabine-induced cytotoxicity is
      warranted.

PMID- 12811512
TI  - Population pharmacokinetics of oral busulfan in children.
AB  - PURPOSE: To characterize the population pharmacokinetics of oral busulfan in 48
      children including pooled data from three transplantation centres with the aim of
      estimating the variability in the kinetics of busulfan and to identify covariates
      that could be used for dose calculation. METHODS: A total of 508 plasma samples
      from 250 administrations (mean 9 samples per patient over 4 days of treatment)
      were collected from 48 children receiving busulfan orally every 6 h. The dosing
      varied between 13 and 20 mg/kg with seven patients receiving a dose of 600
      mg/m(2). The busulfan formulations administered varied considerably. They
      included 2-mg tablets (Myleran), gelatine capsules, crushed tablets suspended in
      water and suspension for administration via nasogastric tube. Samples were
      analysed for busulfan either by HPLC using postcolumn photolysis or by LC-MS.
      Plasma concentration-time data were analysed by population pharmacokinetic
      modelling using NONMEM. RESULTS: Busulfan kinetics were best described by a one
      compartment model (subroutine ADVAN 2 TRANS 2). Residual variability was modelled
      using a combined additive and proportional error model. The influence of
      different covariates on the pharmacokinetic parameters was tested. The best
      results were obtained by inclusion of body surface area (BSA) as a covariate for
      clearance (Cl/F) and volume of distribution (V/F). The final population estimates
      were: Cl/F 4.13 l/h per m(2) +/-26%, V/F 21.3 l/m(2) +/-31% and ka 1.31 h(-1) +/
      110% (population mean +/- interindividual variability, IIV). Variability in one
      patient during the 4 days of treatment (interoccasion variability, IOV) for Cl/F
      (10%) and V/F (19%) were calculated to be less than interindividual variability,
      fulfilling the condition for individualization of busulfan dosage regimens.
      CONCLUSIONS: In our paediatric population, BSA, not body weight, is the best
      predictor of Cl/F and V/F. Our final estimations reflect the wide interpatient
      variability after oral administration of busulfan with an IIV for ka of 110%.

PMID- 12811513
TI  - Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients
      with advanced malignancy.
AB  - PURPOSE: We performed a phase I trial of carboplatin and paclitaxel in
      combination with gemcitabine in order to determine the tolerability of this
      triplet. METHODS: Enrolled in the study were 26 patients with advanced cancer,
      most with non-small cell lung cancer. The patients received escalating doses of
      carboplatin and paclitaxel on day 1 and gemcitabine (30-min infusion) on days 1,
      8, and 15 of a 28-day treatment cycle. The doses of each drug ranged from an area
      under the concentration-time curve (AUC) of 5 to 6 for carboplatin, 135 to 175
      mg/m(2) for paclitaxel, and 300 to 1000 mg/m(2) for gemcitabine. RESULTS:
      Hematologic toxicity was the most commonly observed toxicity and was dose
      limiting. During the first cycle at the recommended phase II dose, there were two
      instances of grade 4 neutropenia and one instance of grade 4 thrombocytopenia
      among six patients, none of which was dose-limiting. Cumulative hematologic
      toxicity emerged in subsequent cycles. Non-hematologic toxicities were mild. Five
      patients, all with previously untreated non-small-cell lung cancer (NSCLC), had a
      partial response. Nine patients with NSCLC or upper gastrointestinal malignancies
      experienced stable disease. CONCLUSIONS: Based on significant neutropenia and
      thrombocytopenia, the regimen recommended for further study consists of
      carboplatin AUC 5, paclitaxel 175 mg/m(2), and gemcitabine 1000 mg/m(2) on a 28
      day cycle. The antitumor activity noted suggests that further investigation of
      this well-tolerated combination in specific tumor types, especially NSCLC, is
      warranted.

PMID- 12811514
TI  - The role of DNA synthesis inhibition in the cytotoxicity of 2',2'-difluoro-2'
      deoxycytidine.
AB  - PURPOSE: Cytotoxicity from the anticancer drug 2',2'-difluoro-2'-deoxycytidine
      (dFdCyd) has been correlated with its incorporation into DNA. However,
      cytotoxicity may also result from inhibition of DNA synthesis, due to either (1)
      dFdCyd diphosphate-mediated inhibition of ribonucleotide reductase, or (2) direct
      inhibition of DNA polymerases by the 5'-triphosphate of dFdCyd (dFdCTP). To
      elucidate the role of DNA synthesis inhibition in the cytotoxicity of dFdCyd, we
      compared dFdCyd to hydroxyurea (HU), a ribonucleotide reductase inhibitor, and
      aphidicolin, an inhibitor of DNA polymerases, in the U251 and D54 human
      glioblastoma cell lines. METHODS: Sensitivity to dFdCyd, HU, and aphidicolin were
      determined using a colony formation assay. The effects of these drugs on DNA
      synthesis were measured by dual parameter flow cytometry, while the effects on
      nucleotide pool levels were analyzed by high-performance liquid chromatography.
      RESULTS: HU and aphidicolin elicited substantially less cytotoxicity than the
      multi-log killing with dFdCyd. When used at equitoxic concentrations (24-h IC50
      values), dFdCyd and HU decreased purine dNTP pools primarily, but dFdCyd was less
      effective than HU. dFdCyd had decreased dATP by about 80% after 4-12 h, and
      required 8-24 h to decrease DNA synthesis by 50%. In contrast, HU rapidly
      depleted dATP by >98% within 2 h, which resulted in >90% inhibition of DNA
      synthesis. Aphidicolin at a concentration similar to its Ki values for DNA
      polymerases (1 microM) decreased DNA synthesis by >70% within 2 h. However, this
      decreased cell survival by only 10% (U251 cells) and 40% (D54 cells).
      CONCLUSIONS: These results demonstrate that HU and aphidicolin produced a more
      rapid and profound inhibition of DNA synthesis than dFdCyd, but resulted in
      significantly less cytotoxicity. This suggests that inhibition of DNA synthesis
      accounted for less than one log of the multi-log cytotoxicity observed with
      dFdCyd, whereas incorporation of dFdCTP into DNA is a more lethal event.

PMID- 12811515
TI  - The topoisomerase I inhibitor topotecan increases the sensitivity of prostate
      tumor cells to TRAIL/Apo-2L-induced apoptosis.
AB  - PURPOSE.:TRAIL/Apo-2L is cytotoxic against numerous prostate tumor cell lines;
      however, some lines are more resistant than others. Identification of an agent
      that increases prostate tumor cell sensitivity to TRAIL/Apo-2L would prove
      valuable for TRAIL/Apo-2L-mediated tumor therapy. Thus, we examined the effect of
      combining five clinically approved chemotherapeutic agents with TRAIL/Apo-2L for
      treating prostate tumor cells. METHODS: Four human prostate tumor cell lines were
      initially tested for TRAIL/Apo-2L sensitivity. Subsequent studies examined
      whether the TRAIL/Apo-2L-induced killing of DU-145 cells was augmented in the
      presence of the chemotherapeutic molecules, as measured by annexin V
      FITC/propidium iodide staining. Furthermore, caspase 8 activation and BID
      cleavage were examined by immunoblotting. RT-PCR and flow cytometry were
      performed to monitor TRAIL-R1 and TRAIL-R2 levels after chemotherapeutic
      treatment. RESULTS: DU-145 cells were the least responsive of the prostate tumor
      cell lines tested to TRAIL/Apo-2L-induced death. Surprisingly, only topotecan, a
      topoisomerase I inhibitor, when used in combination with rTRAIL/Apo-2L led to
      significant apoptosis of DU-145 cells, as measured by caspase 8 activation, BID
      cleavage, and annexin V-FITC/PI staining. Topotecan alone had little to no
      toxicity on the DU-145 cells. Furthermore, the increase in TRAIL/Apo-2L
      sensitivity following topotecan treatment correlated with increased expression of
      TRAIL-R1 and TRAIL-R2 and decreased intracellular levels of the antiapoptotic
      protein survivin. CONCLUSIONS: Our results define a promising direction for
      alternative therapies against androgen-independent prostate cancers. The
      sensitivity of DU-145 cells to TRAIL/Apo-2L was dramatically increased when
      combined with topotecan, suggesting that low-dose topotecan treatment to
      upregulate TRAIL-R1 and TRAIL-R2 and downregulate survivin, followed by TRAIL/Apo
      2L administration, may be a viable therapy for treating cancer of the prostate.

PMID- 12811516
TI  - Challenges with linezolid therapy and reversible pancytopenia.

PMID- 12811517
TI  - Fournier's gangrene.

PMID- 12811523
TI  - Osseointegration in hip prostheses: experimental study in sheep.
AB  - Sixteen 2- to 3-year-old sheep were submitted to a hemiarthroplasty of the hip
      joint with a specially designed femoral component. The proximal two thirds of the
      stem had a circumferential, plasma-sprayed, porous coating with hydroxyapatite.
      The animals where killed a 15, 30, 60, 90, 120, 180, 200, 270, 360, and 540 days
      after surgery. Femurs were submitted to plain radiographs, computerised
      tomography (CT) scan, and dual energy X-ray absorptiometry (DEXA). Cross-sections
      were obtained at four different levels and studied using scanning electron
      microscopy. In the coated portion of the stem, apposition of woven immature bone
      was evident at 15-30 days and mature lamellar bone by 30 days. With time, the gap
      between the endosteum and the coated surface was filled by bridges of lamellar
      bone with a marked trabecular orientation. In the distal uncoated portion of the
      stem, the implant was initially surrounded by fibrous tissue that, with time,
      transformed into lamellar bone.

PMID- 12811524
TI  - Repair of a resistant tibial non-union with a recombinant bone morphogenetic
      protein-7 (rh-BMP-7).

PMID- 12811525
TI  - Ilizarov external fixator for open fractures of the tibial shaft.
AB  - Between December 1993 and 1999 we treated 34 open tibial diaphyseal fractures.
      Thirty patients were available for evaluation with a mean follow-up after
      fracture union of 40.5 (24-80) months. Patient average age was 33.1 (15-71)
      years. Two fractures were grade I, 16 grade II, six grade IIIA, five grade IIIB
      and one grade IIIC. The wound was debrided and the bone fixed with Ilizarov
      device. Soft-tissue healing was achieved through Z-plasty, delayed primary
      closure, split-thickness skin grafting, pedicle flaps and skin traction, and all
      fractures united with an average 5.6 (3-15.4) months. In 28 patients the results
      were excellent and good, in one fair and in one poor. Despite numerous
      complications the use of Ilizarov external fixator provides initial and
      definitive fracture stability.

PMID- 12811528
TI  - Enhanced expression of the complement regulatory protein CD55 predicts a poor
      prognosis in colorectal cancer patients.
AB  - This study prospectively correlated the level of expression of CD55 on tumours
      with 7-year survival in 136 colorectal cancer patients. Patients with tumours
      expressing high levels of CD55 had a significantly worse survival (24%) than
      patients with low CD55 levels (50%, p<0.02). A similar difference was seen for
      patients (Duke's B or C) with a high risk of recurrence (29% vs 58%, p<0.05).
      Furthermore, there was a progressive deterioration in prognosis with increasing
      antigen expression ( p=0.01). It remains unclear if CD55 is overexpressed by
      tumours to protect them from complement or if it is related to the recent
      observation that CD55 is a ligand for the T-cell activation antigen CD97.
      However, it is a marker of aggression, as colorectal cancer patients whose
      tumours overexpress CD55 have a significantly reduced 7-year survival.

PMID- 12811527
TI  - A preclinical study comparing approaches for augmenting the immunogenicity of a
      heptavalent KLH-conjugate vaccine against epithelial cancers.
AB  - Previously using a series of monovalent vaccines, we demonstrated that the
      optimal method for inducing an antibody response against cancer cell-surface
      antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin
      (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH
      conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H,
      Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing
      this vaccine in the clinic, we tested the impact on antibody induction of
      administering the individual conjugates plus adjuvant compared with a mixture of
      the seven conjugates plus adjuvant, and of several variables thought to augment
      immunogenicity. These include approaches for decreasing suppressor cell activity
      or increasing helper T-lymphocyte activity (low dose cyclophosphamide or anti
      CTLA-4 MAb), different saponin adjuvants at various doses (QS-21 and GPI-0100),
      and different methods of formulation (lyophilization and use of polysorbate 80).
      We find that: (1). Immunization with the heptavalent-KLH conjugate plus GPI-0100
      vaccine induces antibodies against the seven antigens of comparable titer to
      those induced by the individual-KLH conjugate vaccines, high titers of antibodies
      against Tn (median ELISA titer IgM/IgG 320/10240), STn (640/5120), TF
      (320/10240), MUC1 (80/20480), and globo H (640/40); while lower titers of
      antibodies against Lewis(y)()(160/0) and only occasional antibodies against GM2
      are induced. (2). These antibodies reacted with the purified synthetic antigens
      by ELISA, and with naturally expressed antigens on the cancer cell surface by
      FACS. (3). None of the approaches for further altering the suppressor cell/helper
      T-cell balance nor changes to the standard formulation by lyophilization or use
      of polysorbate 80 had any impact on antibody titers. (4). An optimal dose of
      saponin adjuvant, QS-21 (50 microg) or GPI-0100 (1000 microg), is required for
      optimal antibody titers. This heptavalent vaccine is sufficiently optimized for
      testing in the clinic.

PMID- 12811529
TI  - Imaging of large vessel vasculitis with (18)FDG PET: illusion or reality? A
      critical review of the literature data.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG PET) plays a
      major role in the management of oncology patients. Owing to the singular
      properties of the glucose tracer, many patients suffering from non-malignant
      diseases such as inflammatory or infectious diseases may also derive clinical
      benefit from the appropriate use of metabolic imaging. Large vessel vasculitides
      such as giant cell arteritis and Takayasu arteritis are other examples that may
      potentially extend the field of (18)FDG PET indications. The purpose of the
      present article is to assess the feasibility of metabolic imaging in vasculitis
      on the basis of the current literature data. In particular, the clinical context
      and the (18)FDG imaging patterns seen in patients with large vessel vasculitis
      are analysed in order to identify potential indications for metabolic imaging.

PMID- 12811530
TI  - Body contour 180 degrees pinhole SPET with or without tilted detector: a phantom
      study.
AB  - This study investigated the feasibility of ordered subsets expectation
      maximisation (OS-EM) reconstruction of 180 degrees pinhole single-photon emission
      tomography (SPET) acquired in body contour mode (variable distance between the
      detector and the axis of rotation for each projection) with or without a tilted
      detector head. Four non-circular orbits were designed bearing in mind the
      rotation radius and tilt angle values of previous pinhole SPET acquisitions in
      patients with circular orbits. The reconstructions were performed using a
      dedicated OS-EM algorithm. Reconstructed images of line and uniformity phantoms
      showed that the spatial and uniformity characteristics of the radioactive objects
      were preserved. In comparison with the circular orbits, the non-circular orbits
      allowed only a moderate gain (maximum 10%) in resolution. However, body contour
      pinhole SPET would significantly facilitate the camera set-up and in this way
      should decrease the camera set-up time, which is an important parameter in
      patient studies.

PMID- 12811531
TI  - Local delivery of (131)I-MIBG to treat peritoneal neuroblastoma.
AB  - Internal radiotherapy involving systemic administration of iodine-131
      metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as
      neuroblastoma has shown considerable success. Although peritoneal seeding of
      neuroblastoma occurs less often than metastases to organs such as the liver, no
      effective treatments exist in this clinical setting. Previous reports have
      demonstrated the effectiveness of peritoneal application of chemotherapeutic
      drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas.
      Local delivery of (131)I-MIBG should produce more favourable dosimetry in
      comparison with its systemic administration in the treatment of peritoneal
      neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma
      was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma
      cells. Two weeks after cell inoculation, comparative biodistribution studies were
      performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated
      with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks.
      Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour
      accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p.
      injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy
      with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean
      survival of untreated mice and mice treated with i.v. administration of (131)I
      MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand,
      radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival
      of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with
      i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of
      (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with
      i.v. injection. These results indicate the benefits of locoregional delivery of
      (131)I-MIBG in the treatment of peritoneal neuroblastoma.

PMID- 12811532
TI  - Liver uptake of free fatty acids in vivo in humans as determined with 14( R, S)
      [18F]fluoro-6-thia-heptadecanoic acid and PET.
AB  - Increased delivery of circulating free fatty acids (FFA) to the liver has been
      implicated in the pathogenesis and progression of diabetes. The liver is
      inaccessible for direct measurement in humans in vivo. We measured liver FFA
      uptake with positron emission tomography (PET) and 14( R, S)-[(18)F]fluoro-6-thia
      heptadecanoic acid ([(18)F]FTHA) in healthy men. We evaluated the use of
      graphical analysis and linear fit to describe uptake data over time, and compared
      the use of metabolite-corrected vs uncorrected input functions. Rapid
      accumulation of tracer in the liver was observed with time, leading to
      progressively higher tissue to blood radioactivity ratios. Using metabolite
      corrected input function curves, linear fit to the data ( r value) exceeded 0.99
      in all subjects, during each fitting time frame. Values of liver FFA influx rate
      constant and uptake were 0.34+/-0.01 ml min(-1) ml(-1) and 0.20+/-0.02 micro mol
      min(-1) ml(-1), respectively, and were minimally affected by the choice of the
      fitting interval. Expressed per unit mass, liver FFA uptake was ~50 times higher
      than that reported in skeletal muscle; in the whole organ, FFA uptake was twice
      as high as in skeletal muscles. The use of metabolite-uncorrected input functions
      significantly worsened the spread of data around the fitted line and led to a
      remarkable underestimation of liver FFA uptake at all time intervals. In
      conclusion, our data provide non-invasive quantification of hepatic FFA uptake in
      humans, showing the liver to handle a high FFA flux. [(18)F]FTHA-PET appears a
      valuable tool for the investigation of hepatic FFA turnover in humans.

PMID- 12811533
TI  - Is PET the future of nuclear medicine?

PMID- 12811534
TI  - Comparative drought-resistance of seedlings of 28 species of co-occurring
      tropical woody plants.
AB  - Quantifying plant drought resistance is important for understanding plant
      species' association to microhabitats with different soil moisture availability
      and their distribution along rainfall gradients, as well as for understanding the
      role of underlying morphological and physiological mechanisms. The effect of dry
      season drought on survival and leaf-area change of first year seedlings of 28
      species of co-occurring woody tropical plants was experimentally quantified in
      the understory of a tropical moist forest. The seedlings were subjected to a
      drought or an irrigation treatment in the forest for 22 weeks during the dry
      season. Drought decreased survival and growth (assessed as leaf-area change) in
      almost all of the species. Both survival and leaf-area change in the dry
      treatment ranged fairly evenly from 0% to about 100% of that in the irrigated
      treatment. In 43% of the species the difference between treatments in survival
      was not significant even after 22 weeks. In contrast, only three species showed
      no significant effect of drought on leaf-area change. The effects of drought on
      species' survival and growth were not correlated with each other, reflecting
      different strategies in response to drought. Seedling size at the onset of the
      dry season had no significant effect on species' drought response. Our study is
      the first to comparatively assess seedling drought resistance in the habitat for
      a large number of tropical species, and underlines the importance of drought for
      plant population dynamics in tropical forests.

PMID- 12811535
TI  - Why do melanin ornaments signal individual quality? Insights from metal element
      analysis of barn owl feathers.
AB  - Melanin-based variation in colour patterns is under strong genetic control and
      not, or weakly, sensitive to the environment and body condition. Current
      signalling theory predicts that such traits may not signal honestly phenotypic
      quality because their production does not entail a significant fitness cost.
      However, recent studies revealed that in several bird species melanin-based
      traits covary with phenotypic attributes. In a first move to understand whether
      such covariations have a physiological basis, we quantified concentrations of
      five chemical elements in two pigmented plumage traits in the barn owl (Tyto
      alba). This bird shows continuous variation from immaculate to heavily marked
      with black spots (plumage spottiness) and from dark reddish-brown to white
      (plumage coloration), two traits that signal various aspects of individual
      quality. These two traits are sexually dimorphic with females being spottier and
      darker coloured than males. We found an enhancement in calcium and zinc
      concentration within black spots compared with the unspotted feather parts. The
      degree to which birds were spotted was positively correlated with calcium
      concentration within spots, whereas the unspotted feather parts of darker reddish
      brown birds were more concentrated in zinc. This suggests that two different
      pigments are responsible for plumage spottiness and plumage coloration. We
      discuss the implications of our results in light of recent experimental field
      studies showing that female spottiness signals offspring humoral response towards
      an artificially administrated antigen, parasite resistance and fluctuating
      asymmetry of wing feathers.

PMID- 12811536
TI  - Leaf dynamics of a deciduous forest canopy: no response to elevated CO2.
AB  - Leaf area index (LAI) and its seasonal dynamics are key determinants of
      terrestrial productivity and, therefore, of the response of ecosystems to a
      rising atmospheric CO(2) concentration. Despite the central importance of LAI,
      there is very little evidence from which to assess how forest LAI will respond to
      increasing [CO(2)]. We assessed LAI and related leaf indices of a closed-canopy
      deciduous forest for 4 years in 25-m-diameter plots that were exposed to ambient
      or elevated CO(2) (542 ppm) in a free-air CO(2) enrichment (FACE) experiment. LAI
      of this Liquidambar styraciflua (sweetgum) stand was about 6 and was relatively
      constant year-to-year, including the 2 years prior to the onset of CO(2)
      treatment. LAI throughout the 1999-2002 growing seasons was assessed through a
      combination of data on photosynthetically active radiation (PAR) transmittance,
      mass of litter collected in traps, and leaf mass per unit area (LMA). There was
      no effect of [CO(2)] on any expression of leaf area, including peak LAI, average
      LAI, or leaf area duration. Canopy mass and LMA, however, were significantly
      increased by CO(2) enrichment. The hypothesized connection between light
      compensation point (LCP) and LAI was rejected because LCP was reduced by [CO(2)]
      enrichment only in leaves under full sun, but not in shaded leaves. Data on PAR
      interception also permitted calculation of absorbed PAR (APAR) and light use
      efficiency (LUE), which are key parameters connecting satellite assessments of
      terrestrial productivity with ecosystem models of future productivity. There was
      no effect of [CO(2)] on APAR, and the observed increase in net primary
      productivity in elevated [CO(2)] was ascribed to an increase in LUE, which ranged
      from 1.4 to 2.4 g MJ(-1). The current evidence seems convincing that LAI of non
      expanding forest stands will not be different in a future CO(2)-enriched
      atmosphere and that increases in LUE and productivity in elevated [CO(2)] are
      driven primarily by functional responses rather than by structural changes.
      Ecosystem or regional models that incorporate feedbacks on resource use through
      LAI should not assume that LAI will increase with CO(2) enrichment of the
      atmosphere.

PMID- 12811537
TI  - The association between Japanese primary open-angle glaucoma and normal tension
      glaucoma patients and the optineurin gene.
AB  - Glaucoma represents one of the most common eye diseases and is characterized by
      progressive loss of visual fields. In the more advanced stages bilateral
      blindness may result, due to optic nerve atrophy and an excavated optic nerve
      head. Open-angle glaucoma is one of the main disease subsets, which may be
      further divided into high tension primary open-angle glaucoma (POAG) and normal
      tension glaucoma (NTG). Recently, the optineurin ( OPTN) gene was identified as a
      causative factor for NTG. Alterations in this gene were found in Caucasian
      families with NTG. In particular, c.458G>A, c.691-692insAG and c.1944G>A were
      shown to be risk factors. Since NTG is reported to be the most common form of
      glaucoma in Japan, and to identify if the OPTN gene plays a role in POAG, the
      DNAs from 148 unrelated Japanese patients with NTG, 165 patients with POAG and
      196 unrelated controls who were not suffering glaucoma were investigated by
      appropriate genotyping techniques. No glaucoma-specific mutations were found in
      the OPTN gene in Japanese glaucoma patients. However, some novel single
      nucleotide polymorphisms (SNPs) in the exons and introns are reported in this
      paper for the first time.

PMID- 12811538
TI  - Comparison of strategies for selecting single nucleotide polymorphisms for
      case/control association studies.
AB  - It is widely believed that a subset of single nucleotide polymorphisms (SNPs) is
      able to capture the majority of the information for genotype-phenotype
      association studies that is contained in the complete compliment of genetic
      variations. The question remains, how does one select that particular subset of
      SNPs in order to maximize the power of detecting a significant association? In
      this study, we have used a simulation approach to compare three competing methods
      of site selection: random selection, selection based on pair-wise linkage
      disequilibrium, and selection based on maximizing haplotype diversity. The
      results indicate that site selection based on maximizing haplotype diversity is
      preferred over random selection and selection based on pair-wise linkage
      disequilibrium. The results also indicate that it is more prudent to increase the
      sample size to improve a study's power than to continuously increase the number
      of SNPs. These results have direct implications for designing gene-based and
      genome-wide association studies.

PMID- 12811539
TI  - Genome-wide homozygosity mapping localizes a gene for autosomal recessive non
      progressive infantile ataxia to 20q11-q13.
AB  - Autosomal recessive ataxias represent genetic and clinical heterogeneity.
      Unsteady gait is often accompanied by poor coordination of limbs, speech, and eye
      movements. To date, seven genes have been identified. In addition, five
      chromosomal loci have been localized in non-related families. Here, we report
      homozygosity mapping of a novel locus to a 19.5-cM region on chromosome 20q11-q13
      in a large inbred Norwegian family with infantile non-progressive ataxia.

PMID- 12811540
TI  - Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence
      for an oxygen-sensing defect.
AB  - Hereditary paraganglioma type 1 (PGL1) is characterized by slow-growing and
      vascularized tumors that often develop in the carotid body (CB) and is caused by
      mutations in the gene for succinate dehydrogenase D ( SDHD) of mitochondrial
      complex II. The mechanisms of tumorigenesis and the factors affecting penetrance
      and expressivity are unknown. Because chronic hypoxic stimulation at high
      altitudes causes sporadic CB paragangliomas, it has been hypothesized that the
      SDHD gene product may be involved in oxygen sensing. On this background, we
      examined genotype-phenotype-environment relationships and tested whether higher
      altitudes adversely affect the phenotype in PGL1. An analysis of 58 subjects from
      23 families revealed that nonsense/splicing mutation carriers developed symptoms
      8.5 years earlier than missense mutation carriers ( P<0.012). We also found that
      subjects who were diagnosed with single tumors at their first clinical evaluation
      lived at lower average altitudes and were exposed to lower altitude-years than
      those with multiple tumors ( P<0.012). Pheochromocytomas developed in six
      subjects (approximately 10%), five of whom had nonsense mutations ( P=0.052).
      Subjects with pheochromocytomas also lived at higher average altitudes and were
      exposed to higher altitude-years than those without them ( P=0.026). To test
      whether altitude is also associated with the more frequent detection of germ-line
      founder mutations among sporadic cases in The Netherlands than in the USA (
      P=0.00033), we calculated population-weighted elevations of the two countries. We
      found that the population-weighted elevations were approximately 260 m for the US
      and 2 m for the central-western Netherlands ( P~0), where three Dutch founder
      mutations were discovered. This finding suggests that low altitudes in The
      Netherlands reduce penetrance and relax the natural selection on SDHD mutations.
      Collectively, these data suggest that higher altitudes and nonsense/splicing
      mutations are associated with phenotypic severity in PGL1 and support the
      hypothesis that SDHD mutations impair oxygen sensing.

PMID- 12811541
TI  - Mutational analysis of the human FATE gene in 144 infertile men.
AB  - The FATE gene maps to Xq28 where one case of a translocation breakpoint has been
      found in an infertile man. Moreover, the FATE promoter contains a putative SF-1
      binding site, and FATE has been proposed as representing a target gene of SF-1 in
      testicular development or germ cell differentiation. This study presents a
      complete mutational screening of the FATE gene in a random group of 144 infertile
      males. Four polymorphisms and two mutations were found. Three of the
      polymorphisms, viz., 741C-->T, 905A-->C, and 3985C-->T, occurred in exon 5 and
      intron 2 and did not alter the deduced polypeptide. One polymorphism resulted in
      the conservative amino acid exchange, A10 V, in 16.0% of the patients. This
      substitution occurred with similar frequencies in the control groups, indicating
      that the mutation does not affect fertility in men or women. The two mutations
      caused the non-conservative amino acid substitutions S125R (patient 1) and I34T
      (patient 2). A family study (patient 1) revealed, however, that S125R was
      inherited and that a fertile male family member carried the mutation. Patient 2
      did not have relevant family members who could be examined. Thus, this study has
      shown that only 1.4% of infertile men have mutations in the FATE gene, and that
      some of these mutations do not singly cause infertility. Hence, FATE may not play
      an important role in the disease-state of infertile men attending fertility
      clinics. However, FATE mutations cannot be excluded as being a contributing
      factor in some cases of male infertility.

PMID- 12811542
TI  - Electroporation of isolated higher-plant mitochondria: transcripts of an
      introduced cox2 gene, but not an atp6 gene, are edited in organello.
AB  - To facilitate the analysis of RNA processing in plant mitochondria, a method was
      established for introducing foreign DNA into mitochondria isolated from maize and
      sorghum. This method permits the uptake of DNA of up to 11 kb into the
      mitochondrial matrix. In vitro incubation of maize mitochondria in a specific
      buffer system was found to permit splicing and editing of newly synthesized RNAs
      for a period of at least 7 h. This was shown both for transcripts of endogenous
      mitochondrial genes (atp6, cox2) and for transcripts derived from an introduced
      Arabidopsis thaliana cox2 gene. In contrast, when a Sorghum bicolor atp6 gene was
      introduced into isolated maize mitochondria, the gene was transcribed, but the
      RNA was not edited, although all the editing sites in maize and sorghum atp6 RNA
      are identical. This may indicate the presence of transcript-specific cis -acting
      regions in the up- or downstream untranslated sequences of the mRNA. The system
      described here should allow further dissection of the mechanism of RNA editing in
      plant mitochondria.

PMID- 12811543
TI  - Praziquantel.
AB  - Praziquantel is the drug of choice for the treatment of all forms of
      schistosomiasis. This review summarizes the main features of the drug, with
      special attention being given to those aspects that may be of interest to the
      practicing physician. After a brief mention of the history, the chemistry, the
      major available brands and their costs, doses and administration schedules are
      reviewed. Pharmacokinetics and drug interactions are analyzed and the low
      toxicity and mild side effects are stressed. A major weakness of praziquantel is
      its relative inefficacy against recent infections, a factor that may occasionally
      result in low cure rates in hyperendemic areas. Recent findings of schistosome
      isolates with a decreased sensitivity to praziquantel are discussed in the
      broader context of a possible emergence of drug resistance.

PMID- 12811544
TI  - Current chemotherapy of human African trypanosomiasis.
AB  - Human African trypanosomiasis is a fatal disease caused by Trypanosoma brucei
      gambiense and Trypanosoma brucei rhodesiense that has re-emerged in recent years.
      However, very little progress has been made in the development of new drugs
      against this disease. Most drugs still in use were developed one or more decades
      ago, and are generally toxic and of limited effectiveness. The most recently
      introduced compound, eflornithine, is only useful against sleeping sickness
      caused by T. b. gambiense, and is prohibitively expensive for the African
      developing countries. We present here an overview of today's approved and
      clinically used drugs against this disease.

PMID- 12811545
TI  - Treatment of microsporidiosis including albendazole.
AB  - Microsporidia are parasitic fungi that can infect not only arthropods and fish,
      but also mammals including humans. This article describes the biology of these
      primitive fungi and gives an overview on recent developments in therapy.
      Encephalitozoonspp. and the species Enterocytozoon bieneusii are most prevalent
      in immunocompromised patients, causing systemic disease or diarrhea. Whereas
      Encephalitozoon infection can usually be effectively treated with albendazole,
      therapeutic approaches for E. bieneusii are still difficult.

PMID- 12811546
TI  - Nitroheterocyclic drugs with broad spectrum activity.
AB  - The group of biologically active nitroheterocyclic compounds includes various 5-
      and 2-nitroimidazoles and 5-nitrofurans, which can be used as therapeutic agents
      against a variety of protozoan and bacterial (anaerobic) infections of humans and
      animals. The current status in the the treatment of giardiasis, trichomoniasis,
      balantidiasis, histomoniasis, and amebiasis (including infections due to
      opportunistic amebas) is presented. The most relevant drugs (benznidazole,
      furazolidone, metronidazole, misonidazole, nifurtimox, nimorazole, nitazoxanide,
      ornidazole, secnidazole, and tinidazole) are characterized with regard to their
      chemical, chemotherapeutic, toxicological, pharmacokinetic, and pharmacological
      properties, including the mechanism of action and resistance in certain parasitic
      protozoa.

PMID- 12811547
TI  - Use of repellents as prophylactic agents.
AB  - Many biting insects are able to transmit diseases or are a regarded as pests. The
      use of repellents is one personal protection measure to avoid to been bitten. The
      first components which were used for this purpose were of plant origin. Some are
      still used, e.g., citronella oil. Systematic evaluation of synthetic repellents
      began during the Second World War. The most important compound resulting from
      these efforts is Deet, followed by less important ones such as dimethylphthalate
      or ethyl hexane diol. Compounds of more recent research are MERCK 3535
      (aminopropionic acid ethylester), p-menthane-3,8 diol, CIC 4 (a lacton) and the
      piperidine derivatives AI3-37220 and Bayrepel (Icaridin). An overview of the
      toxicity and efficacy is given. A chance to improve the cosmetic properties and
      long duration efficacy is the development of new formulations. Applications other
      than the dermal one are the use of repellents as slow release formulations to
      achieve a long range effect and the development of systemic compounds, which are
      taken orally. To date, neither strategy has led to successful solutions.

PMID- 12811548
TI  - Eflornithine for the treatment of human African trypanosomiasis.
AB  - Eflornithine is the only new molecule registered for the treatment of human
      African trypanosomiasis over the last 50 years. It is the drug used mainly as a
      back-up for melarsoprol refractory Trypanosoma brucei gambiense cases. The most
      commonly used dosage regimen for the treatment of T. b. gambiensesleeping
      sickness consists of 100 mg kg(-1) body weight at intervals of 6 h for 14 days
      (150 mg kg(-1) body weight in children) of eflornithine given as short infusions.
      Its efficacy against Trypanosoma brucei rhodesiense is limited due to the innate
      lack of susceptibility of this parasite based on a higher ornithine decarboxylase
      turnover. Adverse drug reactions during eflornithine therapy are frequent and the
      characteristics are similar to other cytotoxic drugs for the treatment of cancer.
      Their occurrence and intensity increase with the duration of treatment and the
      severity of the general condition of the patient. Generally, adverse reactions to
      eflornithine are reversible after the end of treatment. They include convulsions
      (7%), gastrointestinal symptoms like nausea, vomiting and diarrhea (10%-39%),
      bone marrow toxicity leading to anemia, leucopenia and thrombocytopenia (25-50%),
      hearing impairment (5% in cancer patients) and alopecia (5-10%). The drug arrests
      embryonic development in mice, rats and rabbits but the extent of excretion into
      breast milk is unknown. The mean half-life is around 3-4 h and the volume of
      distribution in the range of 0.35 l kg(-1). Renal clearance is about 2 ml min kg(
      1) (i.v.) and accounts for more than 80% of drug elimination. Bioavailability of
      an orally administered 10 mg kg(-1) dose was estimated at 54%. One of the major
      determinants of successful treatment seems to be the cerebrospinal fluid drug
      level reached during treatment, and it was shown that levels above 50 micro mol
      l(-1) must be reached to attain the consistent clearance of parasites. Based on
      its trypanostatic rather than trypanocidal mode of action, it is a rather slow
      acting drug.

PMID- 12811550
TI  - Pseudo-Bartter syndrome in a neonate on prostaglandin infusion.
AB  - We describe a case of iatrogenic pseudo-Bartter syndrome caused by administration
      of prostaglandin E1 (PGE1 alprostadil). Although the use of i.v. PGE1 is a well
      established pharmacological therapy in neonates with a ductus-dependent
      congenital cardiopathy to ensure ductus-dependent flow, we could only find one
      other report on pseudo-Bartter syndrome related to PGE1 infusion. CONCLUSION:
      Primary Bartter syndrome is associated with endogenous increased levels of
      prostaglandins. Therefore, we postulate that the dose of prostaglandin E1
      administered, immaturity and the genetic background are all relevant factors
      involved in the phenotypic presentation of iatrogenic pseudo-Bartter syndrome in
      this preterm infant.

PMID- 12811549
TI  - Octreotide acts as an antitumor angiogenesis compound and suppresses tumor growth
      in nude mice bearing human hepatocellular carcinoma xenografts.
AB  - PURPOSE: To investigate the effect of octreotide on angiogenesis induced by human
      hepatocellular carcinoma (HCC) and to evaluate whether octreotide can suppress
      tumor growth in nude mice bearing human HCC xenografts through inhibition of
      angiogenesis. METHODS: Using MTT assay, invasion assay, migration assay, and
      Matrigel assay, the effects of octreotide on endothelial cells stimulated by
      vascular endothelial growth factor (VEGF) were evaluated in vitro. MTT assay was
      also used to investigate the effects of octreotide on human HCC cells with high
      (MHCC97-H) and low (MHCC97-L) metastatic potential that were established from the
      animal model of human HCC LCI-D20 in nude mice. The expression of somatostatin
      receptor (SSTR) subtypes in human umbilical vein endothelial cells (HUVECs),
      MHCC97-H, and MHCC97-L cells was detected by RT-PCR analysis. An LCI-D20 corneal
      micropocket model in nude mice was used to evaluate the effect of octreotide on
      angiogenesis induced by human HCC in vivo. Male nude mice were subcutaneously
      implanted with LCI-D20 tumor tissues for the tumor xenograft studies. Microvessel
      density was analyzed in CD34-stained tumor sections by the immunohistochemical SP
      method. RESULTS: In vitro, octreotide inhibited the proliferation, invasion, and
      differentiation of HUVECs elicited by VEGF. RT-PCR analysis demonstrated that
      HUVECs expressed the somatostatin receptor subtype SSTR3. In vivo, octreotide was
      sufficiently potent to suppress nude mice corneal neovascularization induced by
      tumor tissues from LCI-D20. Systemic administrations of octreotide produced a
      significant suppression of the growth of LCI-D20. In cell culture, MHCC97-H and
      MHCC97-L cells were insensitive to octreotide at concentrations that
      significantly inhibited endothelial cells proliferation. The HCC cells used did
      not express any known SSTRs. Immunohistochemical studies of tumor tissues
      revealed decreased microvessel density in octreotide-treated animals as compared
      with controls. CONCLUSIONS: The present study demonstrates that the somatostatin
      analogue octreotide is a potent antitumor angiogenesis compound and the
      antiproliferative effect of octreotide on tumor growth in nude mice bearing HCC
      xenografts may be mediated, at least in part, by its suppressive effect on blood
      vessel supply. The somatostatin analogue octreotide might provide a useful and
      relatively nontoxic adjuvant therapy in the treatment of HCC.

PMID- 12811551
TI  - Occurrence of overwhelming gram-negative infections in splenectomised patients
      with thalassaemia major.

PMID- 12811552
TI  - A child with Kawasaki disease who survived after rupture of a coronary artery
      aneurysm.

PMID- 12811553
TI  - Virilising adrenocortical tumours in children.
AB  - Adrenocortical tumours (ACT) are a rare but important cause of virilisation in
      infancy and childhood. Four cases of virilising ACT are presented. Two girls (age
      0.9 years and 3.9 years) and two boys (age 6.2 years and 6.4 years) had symptoms
      and signs of virilisation before the age of 6 years. Diagnosis of a virilising
      adrenal tumour was confirmed by laboratory tests, diagnostic imaging and
      histology. However, one female patient was misdiagnosed and treated for 3 months
      as atypical congenital adrenal hyperplasia. Ultrasonography of the adrenal region
      could not visualise the tumour in three out of four cases. The most sensitive
      method of diagnostic imaging was MRI. In all cases, treatment consisted of
      complete surgical resection of the adrenal tumour by open abdominal surgery.
      Immunohistochemistry was performed in all patients and in two patients there was
      an overexpression of p53, indicating p53 mutation and in three cases the ki67
      proliferation index was greater than 5%. The classification of ACT in childhood
      is extremely difficult. Histology scores adapted from adrenal tumours in adults
      and molecular markers are under investigation, but there is still not enough
      clinical experience since ACT are so rare. CONCLUSION: Long-term follow-up is
      mandatory not only because of the uncertainty in classification of adrenocortical
      tumours, but also for observation of growth and pubertal development.

PMID- 12811554
TI  - Changes in fat mass, fat-free mass and aerobic fitness in severely obese children
      and adolescents following a residential treatment programme.
AB  - The purpose of this study was to describe changes in fat mass (FM), fat-free mass
      (FFM) and aerobic fitness in severely obese children and adolescents during
      residential treatment in the Medical Paediatric Centre Zeepreventorium. Treatment
      consisted of moderate dietary restriction, physical activity and psychological
      support. This study was a clinical observation of 20 severely obese children and
      adolescents (8 boys and 12 girls, aged 15.4+/-1.8 years) who completed the 10
      month residential programme. Height, weight, FM, FFM and aerobic fitness was
      measured four times during the intervention: at baseline, 11 weeks, 24 weeks and
      at 33 weeks (at the end of the programme ). The mean decrease in level of
      overweight was 46% (P<0.001), with a mean loss of 8.9% FM (P<0.001). Submaximal
      performance (PWC150) improved from 123+/-35 Watt to 152+/-37 Watt (P<0.001).
      Maximal performance levels increased (performance time: from 14+/-2.9 min to
      15.3+/-3.5 min, peak power: from 186+/-38 Watt to 205+/-45 Watt, P<0.01) without
      an improvement in absolute VO(2 peak). CONCLUSION: A moderate dietary restriction
      in combination with physical activity and psychological support in severely obese
      children and adolescents is effective in decreasing body fat and improving
      physical performance. Further research is needed to evaluate the longer-term
      effects of such a programme.

PMID- 12811555
TI  - Temporary changes in macrophages and MHC class-II molecule-expressing cells in
      the tubulointerstitium in response to uranyl acetate-induced acute renal failure
      in rats.
AB  - The present study was designed to asses the dynamic changes in macrophages (Mos)
      with or without expression of major histocompatibility complex (MHC) class-II
      molecule in response to uranyl acetate-induced acute renal failure (ARF) in rats.
      ED1+ monocytes/Mos infiltrated into the interstitium as early as day 2, peaked in
      number on day 5 after uranyl acetate-induced ARF. ED1+ cells did not correlate
      with necrotic tubules but accumulated abundantly in the vicinity of the Ki67+
      regenerating proximal tubules around days 4-5. Afterward, regeneration of
      proximal tubules was accelerated. After day 5, some ED1+ cells entered the
      tubular lumen, and became ED1+ giant cells, which had features of phagocytic Mos
      by immunoelectron microscopy, peaking in number on day 7. Most ED1+ cells did not
      incorporate [(3)H]-thymidine, indicating lack of active proliferation. The number
      of OX6+ cells (directed to MHC class-II molecule) in the interstitium
      significantly increased on day 4 and peaked on day 5. Double staining revealed
      that ED1+OX6- cells entered the tubular lumen while ED1+OX6+ cells remained in
      the peritubular regions. Osteopontin (OPN) protein and mRNA were significantly
      upregulated. No specific relationship could be found between OPN+ regenerating
      proximal tubules and ED1+ cells, but most ED1+ giant cells were OPN+ and
      intermingled among OPN+ cell debris. Our findings suggest that ED1+ Mos are
      actively associated with regenerating proximal tubules and, thus, might promote
      proximal tubular regeneration. ED1+OX6- Mos may function as scavengers and
      phagocytose cellular debris in the tubular lumen, cleaning the wound site. OPN
      might be involved in this process. ED1+OX6+ Mos in the peritubular regions may
      act as outpost of the defense system to monitor incoming antigens. Our data
      indicate that Mos with or without expressing MHC class-II molecule contribute to
      the defense and repair of injured proximal tubules in this ARF.

PMID- 12811556
TI  - Molecular evolution of C4 phosphoenolpyruvate carboxylase in the genus Flaveria-
      a gradual increase from C3 to C4 characteristics.
AB  - In order to elucidate the discrete steps in phospho enolpyruvate carboxylase
      (PEPC) evolution concerning K(m)-PEP and malate tolerance a comparison was made
      between C3, C3-C4 and C4 species of the dicot genus Flaveria. The PEPCs of this
      genus are encoded by a gene family comprising three classes: ppcA, ppcB and ppcC
      [J. Hermans and P. Westhoff (1990) Mol Gen Genet 224:459-468, (1992) Mol Gen
      Genet 234:275-284]. The ppcA of F trinervia (C4) codes for the C4 PEPC isoform
      but other plants of the genus contain ppcA orthologues too. The C3 plant F.
      pringlei showed the lowest levels of ppcA PEPC mRNA followed by F. pubescens (C3
      C4) while the C4-like plant F. brownii displayed RNA amounts close to the C4
      species F. trinervia. In contrast to the similar expression profiles of F.
      brownii (C4-like) and F. trinervia (C4) the PEPC amino acid sequence of F.
      brownii was more similar to the C3 and C3-C4 ppcA PEPCs than to the C4 PEPC.
      Similarly, the C3, C3-C4 and C4-like ppcA PEPCs showed almost identical PEP
      saturation kinetics when activated by glucose-6-phosphate ( K(m)-PEP: 17-20
      microM) while the K(m)-PEP for the C4 PEPC was determined to be 53 microM.
      However, without activation the ppcA PEPCs of F. pubescens and F. brownii
      displayed C3-C4 intermediate values. A similar picture was obtained when the
      malate sensitivities were compared. In the non-activated state the F. trinervia
      (C4) enzyme was 10 times more tolerant to malate than the F. pringlei
      counterpart. The ppcA enzymes of F. pubescens (C3-C4) and F. brownii (C4-like)
      displayed intermediate values. In contrast, the inclusion of 5 mM glucose-6
      phosphate in the reaction mixture changed the order totally. Interestingly, the
      activation rendered the C4 enzyme about 50% less tolerant to malate than the C3
      PEPC. The activation had a positive effect on malate tolerance of the F.
      pubescens (C3-C4) PEPC while the ppcA PEPC of F. brownii (C4-like) was almost
      unaffected.

PMID- 12811557
TI  - EcFLO, a FLORICAULA-like gene from Eschscholzia californica is expressed during
      organogenesis at the vegetative shoot apex.
AB  - FLORICAULA/ LEAFY-like genes were initially characterized as flower meristem
      identity genes. In a range of angiosperms, expression occurs also in vegetative
      shoot apices and developing leaves, and in some species with dissected leaves
      expression is perpetuated during organogenesis at the leaf marginal blastozone.
      The evolution of these expression patterns and associated functions is not well
      understood. We have isolated and characterized a FLORICAULA-like gene from
      California Poppy, Eschscholzia californica Cham. (Papaveraceae), a species
      belonging to the basal eudicot clade Ranunculales. EcFLO encodes a putative 416
      amino-acid protein with highest similarity to homologous genes from Trochodendron
      and Platanus. We show that EcFLO mRNA is expressed during the vegetative phase of
      the shoot apical meristem and in developing dissected leaves in a characteristic
      manner. This pattern is compared to that of other eudicots and discussed in terms
      of evolution of FLORICAULA expression and function.

PMID- 12811558
TI  - Cell differentiation, secondary cell-wall formation and transformation of callus
      tissue of Pinus radiata D. Don.
AB  - Tracheid and sclereid differentiation was induced in callus cultures of Pinus
      radiata D. Don by culturing on a basal medium containing activated charcoal but
      no phytohormones; sclereids differentiated in callus derived from xylem strips,
      but not in callus derived from hypocotyl segments. The tracheids differentiated
      in hypocotyl-derived callus had helical, scalariform, reticulated or pitted
      secondary cell-wall patterns, but those differentiated in xylem-derived callus
      had a reticulate or pitted pattern. The thickened tracheid and sclereid walls
      contained lignin as indicated by the red colour reaction given with
      phloroglucinol-HCl. The presence of lignin in the cell walls of differentiated
      callus was confirmed using pyrolysis gas chromatography-mass spectrometry by the
      detection of phenylpropanoid components derived from lignin. Lignin was also
      detected using solid-state (13)C cross-polarisation/magic-angle spinning nuclear
      magnetic resonance spectroscopy and quantified as thioglycolic acid lignin.
      Monosaccharide analyses of the cell walls isolated from differentiated and
      undifferentiated calli showed that the cell walls of the differentiated calli
      contained higher proportions of glucose and mannose, consistent with the presence
      of greater proportions of gluco- and/or galactogluco-mannans in the secondary
      cell walls of the differentiated cells. A protocol for the stable transformation
      of undifferentiated, xylem-derived cultures was successfully developed.
      Transgenic cell lines were established following Biolistic particle bombardment
      with a plasmid containing the coding region of the nptII gene and the coding
      region of the cad gene from P. radiata. Expression of the nptII gene in
      transgenic lines was confirmed by an NPTII-enzyme-linked immunosorbent assay. The
      overexpression of cad in the transgenic lines resulted in a down-regulation of
      cinnamyl alcohol dehydrogenase (EC 1.1.1.195) expression.

PMID- 12811559
TI  - Ecophysiological aspects of allelopathy.
AB  - Allelochemicals play an important role in explaining plant growth inhibition in
      interspecies interactions and in structuring the plant community. Five aspects of
      allelochemicals are discussed from an ecophysiological perspective: (i)
      biosynthesis, (ii) mode of release, (iii) mode of action, (iv) detoxification and
      prevention of autotoxicity, and (v) joint action of allelochemicals. A discussion
      on identifying a compound as an allelochemical is also presented.

PMID- 12811560
TI  - Organic anion transport is the primary function of the SLC17/type I phosphate
      transporter family.
AB  - Recently, molecular studies have determined that the SLC17/type I phosphate
      transporters, a family of proteins initially characterized as phosphate carriers,
      mediate the transport of organic anions. While their role in phosphate transport
      remains uncertain, it is now clear that the transport of organic anions
      facilitated by this family of proteins is involved in diverse processes ranging
      from the vesicular storage of the neurotransmitter glutamate to the degradation
      and metabolism of glycoproteins.

PMID- 12811561
TI  - Estrogen modulates ClC-2 chloride channel gene expression in rat kidney.
AB  - ClC-2 is a CLC family member of chloride channels sensitive to changes in cell
      volume, pH and voltage. The ClC-2 is widely distributed along the nephron
      although in the kidney its role still not well understood. Aldosterone studies
      suggest that ClC-2 expression in the kidney may be hormonally regulated. To
      explore the possibility that estrogen control ClC-2 expression, we investigated
      whether its expression changed in the kidney of female Wistar rats subjected to
      ovariectomy with or without near-physiological or high doses of 17beta-estradiol
      benzoate treatment for 10 days. Total RNA isolated from rat kidney and dissected
      nephron segments was analyzed by ribonuclease protection assay and/or a semi
      quantitative RT-PCR. The renal ClC-2 protein expression was analyzed by Western
      blot. The decreased renal expression of ClC-2 mRNA and protein observed in
      ovariectomized rats was restored to control levels after treatment with low doses
      of estradiol. Higher dose estradiol lead to an even greater increase in ClC-2
      mRNA and protein expression. This change in overall expression was shown to be
      caused by the modulation of ClC-2 mRNA expression in the proximal tubule. These
      results suggest that ClC-2 may be involved in estrogen-induced Cl(-) transport in
      rat kidney.

PMID- 12811562
TI  - The human sugar-phosphate/phosphate exchanger family SLC37.
AB  - The SLC37 family of four predicted proteins is an almost unexplored group of
      transmembrane sugar transporters. Of the four proteins/genes assigned to date to
      this family, only one is well known, the SLC37A4 gene (also known as the glucose
      6-phosphate transporter 1, G6PT1) mutated in the glycogen storage disease non-1A
      type. Data on SLC3A1 gene expression are available for humans, while data on
      SLC37A2 are available for mice. The last SLC37 family member, SLC37A3, is only a
      putative gene/protein identified by in silico analyses. The four genes are not
      clustered in a single chromosome as regions and the identity of their predicted
      polypeptides is between 60 and 20%. Here we propose a new nomenclature for the
      SLC37 proteins (SPX: sugar- phosphate e xchangers) numbered according to the gene
      numbering.

PMID- 12811563
TI  - Effect of acute hypoxia on ATP-sensitive potassium currents in substantia
      gelatinosa neurons of juvenile rats.
AB  - Although hypoxia is known to affect membrane excitability of various neurons by
      various mechanisms, the effects of hypoxia on substantia gelatinosa (SG) neurons
      have not yet been elucidated. In whole-cell or perforated patch-clamp recordings
      from SG neurons, we showed that acute hypoxia induces a reversible
      hyperpolarization of -6.1+/-1.3 mV of the resting membrane potential and an
      outwards current of 9.48+/-1.71 pA at a holding potential of -60 mV. The reversal
      potentials of the hypoxia-induced current depended on [K(+)](o). The hypoxia
      induced hyperpolarization and outwards current were abolished completely by
      BaCl(2), but not by CsCl. Glibenclamide, a blocker of K(ATP) channels, blocked
      the hypoxia-induced hyperpolarization. Pretreatment with cromakalim, an opener of
      K(ATP) channels, occluded the hypoxia-induced hyperpolarization. Any alteration
      by hypoxia was not observed in the presence of an internal solution with a high
      [ATP] (10 mM). The above results suggest that hypoxia-induced hyperpolarization
      in SG neurons is mediated by activation of K(ATP) channels.

PMID- 12811564
TI  - Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase
      function in skinned rat slow- and fast-twitch fibres.
AB  - The effects of anabolic-androgenic steroid administration on the function of the
      sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres
      from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats.
      Twenty male rats were divided into two groups, one group received an
      intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8
      weeks, the second received similar weekly doses of vehicle (sterile peanut oil).
      Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+)
      loading in EDL and soleus fibres by 49% and 29%, respectively. In control and
      treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+)
      loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was
      not significantly modified by nandrolone decanoate treatment. Nandrolone
      decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type
      dependent manner.

PMID- 12811565
TI  - Incisional hernia repair after orthotopic liver transplantation: a technique
      employing an inlay/onlay polypropylene mesh.
AB  - BACKGROUND: The literature provides no data on the incidence and operative
      management of incisional hernias developing after orthotopic liver
      transplantation. The use of high-dose immunosuppressive agents results in an
      appreciable delay in wound healing. There is thus a need for a procedure for the
      reconstruction of the abdominal wall for patients on immunosuppression. The aim
      of this retrospective study was to establish the incidence of incisional hernias
      and an analysis of the results after implantation of a polypropylene mesh in
      inlay-onlay technique after liver transplantation is given. METHODS: The basis
      for the present retrospective investigations was a total of 207 liver
      transplantations carried out in 192 patients (15 re-transplantations). After
      performing tensiometry, a polypropylene mesh (Marlex) was implanted to close the
      hernias using the inlay/onlay technique or a direct closure of the fascia was
      done. All treated hernias were followed up for a median of 18 months. RESULTS:
      Among 184 patients, 17 developed incisional hernias after primary direct closure
      of the abdominal wall, giving an incidence of 9%. In an additional 8 patients an
      incisional hernia was seen where an absorbable mesh was used to close the
      abdominal wall after liver transplantation. In addition, there were 25 incisional
      hernias after 207 liver transplantations (12%). One of 15 (7%) of the surgically
      repaired hernias with implantation of a polypropylene mesh (Marlex) developed a
      recurrence. All the 3 patients after direct apposition of the fascia without
      using a polypropylene mesh suffered a recurrence (3 of 3; 100%). Significant risk
      factors for developing an incisional hernia were the amount of ascites and the
      stay in the ICU after transplantation. Neither severe deep nor superficial wound
      infection nor bowel fistulas were observed after implantation of a inlay/onlay
      mesh. CONCLUSION: In patients after liver transplantation, the implantation of a
      polypropylene mesh proved to be an efficient and safe method of treating
      incisional hernias. Implantation of a mesh was not associated with an increased
      infection rate, despite the use of immunosuppression. In view of the high
      recurrence rate associated with primary closure, mesh implantation should be
      given preference.

PMID- 12811566
TI  - Effects of increased intensity of intermittent training in runners with differing
      VO2 kinetics.
AB  - The purpose of this study was to test the hypothesis that athletes having a
      slower oxygen uptake ( VO(2)) kinetics would benefit more, in terms of time spent
      near VO(2max), from an increase in the intensity of an intermittent running
      training (IT). After determination of VO(2max), vVO(2max) (i.e. the minimal
      velocity associated with VO(2max) in an incremental test) and the time to
      exhaustion sustained at vVO(2max) ( T(lim)), seven well-trained triathletes
      performed in random order two IT sessions. The two IT comprised 30-s work
      intervals at either 100% (IT(100%)) or 105% (IT(105%)) of vVO(2max) with 30-s
      recovery intervals at 50% of vVO(2max) between each repeat. The parameters of the
      VO(2) kinetics (td(1), tau(1), A(1), td(2), tau(2), A(2), i.e. time delay, time
      constant and amplitude of the primary phase and slow component, respectively)
      during the T(lim) test were modelled with two exponential functions. The highest
      VO(2) reached was significantly lower ( P<0.01) in IT(100%) run at 19.8 (0.9)
      km(.)h(-1) [66.2 (4.6) ml(.)min(-1.)kg(-1)] than in IT(105%) run at 20.8 (1.0)
      km(.)h(-1) [71.1 (4.9) ml(.)min(-1.)kg(-1)] or in the incremental test [71.2
      (4.2) ml(.)min(-1.)kg(-1)]. The time sustained above 90% of VO(2max) in IT(105%)
      [338 (149) s] was significantly higher ( P<0.05) than in IT(100%) [168 (131) s].
      The average T(lim) was 244 (39) s, tau(1) was 15.8 (5.9) s and td(2) was 96 (13)
      s. tau(1) was correlated with the difference in time spent above 90% of VO(2max)
      ( r=0.91; P<0.01) between IT(105%) and IT(100%). In conclusion, athletes with a
      slower VO(2) kinetics in a vVO(2max) constant-velocity test benefited more from
      the 5% rise of IT work intensity, exercising for longer above 90% of VO(2max)
      when the IT intensity was increased from 100 to 105% of vVO(2max).

PMID- 12811567
TI  - Parasympathetic heart rate modulation during parabolic flights.
AB  - During parabolic flight short periods of microgravity and hypergravity are
      created. These changes influence cardiovascular function differently according to
      posture. During the 29th parabolic flight campaign of the European Space Agency
      (ESA), the electrocardiogram (ECG) was recorded continuously in seven healthy
      volunteers in two positions (standing and supine). Five different phases were
      differentiated: 1 g (1 g=9.81 m/s(2)) before and after each parabola, 1.8 g at
      the ascending leg of the parabola (hypergravity), 0 g at the apex, 1.6 g at the
      descending leg (hypergravity). We assessed heart rate variability (HRV) by
      indices of temporal analysis [mean RR interval (meanRR), the standard deviation
      of the intervals (SDRR), and the square root of the mean squared differences of
      successive intervals (rMSSD) and coefficient of variation (CV)]. In the supine
      position no significant differences were shown between different gravity phases
      for all HRV indices. In the standing position the 0 g phase showed a tendency
      towards higher values of meanRR compared to the control and to the other phases (
      p=NS). SDRR, rMSSD and CV were significantly higher compared to control (
      p<0.05). Significantly higher values for meanRR in the supine position at 1 g and
      hypergravity ( p<0.05) were found when compared to standing. SDRR was
      significantly higher at 0 g in the standing position compared to supine [95 (44)
      ms vs. 50 (15) ms; p<0.05] and lower in other phases. rMSSD and CV showed the
      same trend ( p=NS). We confirm that, during parabolic flights, position matters
      for cardiovascular measurements. Time domain indices of HRV during different
      gravity phases showed: (1) higher vagal modulation of the autonomic nervous
      system in microgravity, when compared with normo- or hypergravity in standing
      subjects; and (2) no differences in supine subjects between different g phases.

PMID- 12811568
TI  - Reduced oxygen uptake increase to work rate increment (DeltaVO2/DeltaWR) is
      predictable by VO2 response to constant work rate exercise in patients with
      chronic heart failure.
AB  - Patients with reduced peak oxygen uptake (VO2) due to chronic heart failure (CHF)
      exhibit abnormal VO2 kinetics even during mild to moderate exercise. This is
      characterized by a reduced ratio of the VO2 increase to the work rate increment
      (DeltaVO2/DeltaWR) during ramp exercise, and by a slow increase in VO2 during
      constant work rate exercise. Because the slow kinetics alone is unlikely to
      explain the reduced DeltaVO2/DeltaWR on theoretical grounds, we can postulate
      that the linearity between work rate and VO2 may be impaired when exercise is
      imposed in a ramp fashion. The present study was designed to address this issue.
      In 21 CHF patients and 17 normal controls, we performed both symptom-limited
      exercise testing (15 W. min(-1) ramp) and a constant work rate exercise test (0 W
      followed by 50-W step). The VO2 step response was used to mathematically derive
      the hypothetical VO2 ramp response by time integration. Although peak VO2 and
      work rate were both significantly lower in patients, the attenuation in peak VO2
      was more prominent ( p<0.05), which could be explained by a lower
      DeltaVO2/DeltaWR in patients compared with controls [8.1 (SD 1.0) and 9.8 (0.5)
      ml. min(-1). W(-1), p<0.01]. The hypothetical DeltaVO2/DeltaWR derived from the
      VO2 step response was also significantly lower in patients [8.7 (1.0) and 10.0
      (0.7) ml. min(-1). W(-1), p<0.01]. The hypothetical and measured DeltaVO2/DeltaWR
      were highly correlated ( r=0.78, p<0.001). Thus, we can reasonably predict the
      VO2 ramp response from the VO2 response to a step increase in work rate,
      indicating that linearity between VO2 and work rate is held constant irrespective
      of loading patterns. Additional studies, such as those including evaluation of
      anaerobic bioenergetics, are needed to further elucidate the precise mechanism(s)
      of this phenomenon.

PMID- 12811569
TI  - EMG and MMG of synergists and antagonists during relaxation at three joint
      angles.
AB  - The aim of the study was to estimate the influence of force changes during
      relaxation from maximal voluntary contraction (MVC) of elbow flexors on
      electrical (EMG) and mechanical (MMG) activity of synergists and antagonists at
      different joint angles. Repeated studies were conducted on 22 young female
      students to estimate the EMG and MMG activity of the biceps brachii (BB),
      brachioradialis (BR), and triceps brachii (TB) muscles during relaxation from MVC
      at an optimal angle (the angle at which a subject achieved MVC=Lo), as well as at
      angles that were smaller (Ls=Lo-30 degrees ) and bigger (Ll=Lo+30 degrees ). Four
      testing sessions consisted of 2-s or 3-s MVC at each angle with simultaneous
      recording of EMG and MMG signals from BB, BR, and TB muscles. The EMG/MMG probes
      were used to record EMG and MMG signals. The results showed that the slow
      relaxation rate was related to a percentage decrease of the EMG amplitude (as
      measured by root mean square; EMG RMS) of the synergists, while the fast
      relaxation was related to the EMG RMS of the antagonist, independent of the joint
      angle. The MMG amplitude (MMG RMS) increased gradually during slow and fast
      relaxation (compared to the MMG RMS at MVC), indicating a bigger muscle
      oscillation during relaxation; the changes were related to the muscle tested and
      joint angle. It was found that, during the slow relaxation, the MMG RMS reflects
      the force amplitude changes in the BB muscle and the velocity of force changes in
      the BB and TB muscle (but not in the BR). During the fast relaxation, the MMG
      amplitude reflects a change in muscle force in the TB and BB muscles (but not in
      the BR), and the velocity of force changes in the synergists (not in the
      antagonist). The different contribution of the force and velocity of force
      changes during slow and fast relaxation to the MMG signal in the three muscle
      tested can be related to the different deactivation time of each muscle. In
      conclusion, the present results indicate that MMG recordings might be useful to
      measure the fast relaxation of individual muscle during voluntary contraction,
      but this needs be tested on isolated muscle.

PMID- 12811571
TI  - Legal regulations of occupational skin protection.
AB  - Legal regulations of occupational skin protection are different in different
      European countries. Some guidelines are compulsory in all countries that belong
      to the European Union, such as "Control of Substances Hazardous to Health" and
      "Personal Protective Equipment". The following presentation gives a survey of
      legal regulations of skin-protection measures in different European countries.
      The information was obtained by addressing the Labour Inspection Authorities in
      all European countries and asking them for detailed information. The above
      mentioned guidelines are referred to, as well as corresponding regulations in
      European countries that do not belong to the European Union. National regulations
      for special substances or worker activities are reported. The survey may help to
      complete or improve national regulations on occupational skin protection, since
      this seems to be a necessary condition to reduce occupational skin diseases.

PMID- 12811570
TI  - The effect of exercise duration and mode on the growth hormone responses in young
      women on oral contraceptives.
AB  - Previous research is conflicting concerning the minimum time duration needed to
      elicit a growth hormone (GH) response to aerobic exercise; thus, the purpose of
      this project was to examine the effects of mode and duration on exercise-induced
      GH responses in young women taking oral contraceptives. Nine healthy young
      females on oral contraceptives exercised at 75% of their mode-specific peak
      aerobic power ( VO(2)peak) on the treadmill and cycle ergometer for 10, 15 and 20
      min, with serial blood samples taken at rest and every 10 min throughout the
      entire 5.5 h of the study. Each exercise bout was followed by 70 min of rest. A
      significant ( P<0.02) GH response was observed at the end of exercise regardless
      of the duration or mode of exercise. The peak GH concentrations were 12.2 (1.8),
      10.2 (1.6), and 7.6 (1.5) ng.ml(-1) for the 10-, 15-, and 20-min exercise bouts
      on the treadmill, respectively. For the cycle ergometer, peak GH concentrations
      were 9.3 (2.0), 6.3 (1.0), and 9.8 (1.7) ng.ml(-1), respectively. The total
      integrated area under the curve was not significantly different between the cycle
      and treadmill exercise for each exercise duration. Moderate-intensity aerobic
      exercise is sufficient to produce a GH response in as little as 10 min during
      both treadmill and cycling exercise in young women taking oral contraceptives.
      Overall, the mode of exercise does not impact the exercise-induced GH response.

PMID- 12811572
TI  - Estradiol receptor binding to the epithelium of uterine lumen and glands: region-
      and time-related changes during preimplantation and periimplantation periods
      studied by autoradiography.
AB  - The presence and changes of estradiol nuclear binding and related functions in
      uterine luminal and glandular epithelium were studied before and after blastocyst
      implantation using receptor autoradiography with (3)H-estradiol-17beta in
      association with (3)H-thymidine incorporation and immunocytochemical binding of
      antibody to estrogen receptor ER-alpha. (3)H-estradiol nuclear binding is present
      but variable during days 1.5-7.5 of pregnancy. Sites of strong nuclear binding of
      (3)H-estradiol exhibit strong immunocytochemical staining with ER-alpha antibody.
      Qualitative and quantitative evaluation of autoradiograms reveal that there is a
      general increase of nuclear (3)H-estradiol binding during the first 3 days after
      fertilization in both luminal and glandular epithelium. The binding of estradiol
      is stronger in glandular epithelium from day 2.5 to day 7.5, paralleled by a rise
      in (3)H-thymidine incorporation on day 2.5. By comparison, in the epithelium of
      the uterine lumen (3)H-estradiol nuclear binding is low, but relatively high in
      epithelial cells at lateral branching of the lumen where the increase in (3)H
      estradiol binding corresponds to an increased labeling index with (3)H-thymidine.
      A highly differentiated binding of (3)H-estradiol to luminal and glandular
      epithelium was demonstrated with region- and time-specific changes of related
      effects on cell proliferation, differentiation, and secretion, probably involving
      involution and remodeling. The strong (3)H-estradiol binding to glandular
      epithelium suggests that estradiol exerts pronounced effects on glandular
      activities in the periimplantation period.

PMID- 12811573
TI  - Protein kinase C isoforms in the enteric nervous system.
AB  - C kinases (PKCs) are a family of enzymes essential for the transduction of
      signals in a diverse range of cell types, including neurons. The different
      isoforms vary in their activation requirements. Therefore, cell-specific
      expression of different isoforms has implications for PKC-mediated control of
      organ function. This study has investigated the types and distributions of PKC
      isoforms in the small intestine of the guinea-pig, with particular emphasis on
      their localisation in myenteric neurons, using immunohistochemistry and western
      blotting techniques. Three PKC isoforms, gamma, eta and theta, were detected in
      the calbindin-immunoreactive subset of intrinsic primary afferent neurons, but
      not in other myenteric neurons. Both gamma and theta immunoreactivities were also
      located in interstitial cells of Cajal. In contrast to these isoforms,
      immunoreactivity for PKCs lambda and epsilon was present in all myenteric neurons
      of the ileum. PKCalpha immunoreactivity was detected primarily in the glial
      network, as shown through double labelling with antibodies to the glial filament
      protein, S100b. Myenteric neurons were also weakly immunoreactive for this
      isoform. PKCdelta immunoreactivity was very highly expressed in smooth muscle,
      but was largely absent from neurons. Immunoreactivity for RACK1, a binding
      protein for PKCbeta, was detected in both calbindin-immunoreactive neurons and in
      smooth muscle cells. This study indicates a selective distribution of PKC
      isoforms to specific cell types. Isoform-specific activity of these enzymes could
      provide a means through which targeted modulation of intestinal function is
      achieved.

PMID- 12811575
TI  - Improper chromosome synapsis is associated with elongated RAD51 structures in the
      maize desynaptic2 mutant.
AB  - The RecA homolog, RAD51, performs a central role in catalyzing the DNA strand
      exchange event of meiotic recombination. During meiosis, RAD51 complexes develop
      on pairing chromosomes and then most disappear upon synapsis. In the maize
      meiotic mutant desynaptic2 (dsy2), homologous chromosome pairing and
      recombination are reduced by ~70% in male meiosis. Fluorescent in situ
      hybridization studies demonstrate that a normal telomere bouquet develops but the
      pairing of a representative gene locus is still only 25%. Chromosome synapsis is
      aberrant as exemplified by unsynapsed regions of the chromosomes. In the mutant,
      we observed unusual RAD51 structures during chromosome pairing. Instead of
      spherical single and double RAD51 structures, we saw long thin filaments that
      extended along or around a single chromosome or stretched between two widely
      separated chromosomes. Mapping with simple sequence repeat (SSR) markers places
      the dsy2 gene to near the centromere on chromosome 5, therefore it is not an
      allele of rad51. Thus, the normal dsy2 gene product is required for both
      homologous chromosome synapsis and proper RAD51 filament behavior when
      chromosomes pair.

PMID- 12811576
TI  - Increased scalp skin lipids in response to antidandruff treatment containing zinc
      pyrithione.

PMID- 12811577
TI  - Autoantibodies in sporadic porphyria cutanea tarda.
AB  - In an investigation of autoimmune antibodies using indirect immunofluorescence
      and Western blot analysis in a group of porphyria cutanea tarda patients we did
      not find any cytosolic antibodies potentially able to inhibit uroporphyrinogen
      decarboxylase. Furthermore, no known etiological factors were present in any of
      our patients. We therefore consider the development of the recently reported
      autoantibody with a molecular weight of 40 kDa a reaction to infection with the
      hepatitis C virus. The origin of mostly antinuclear antibodies against liver
      antigens (50, 45 and 56 kDa), detected in seven patients, was not identified and
      their etiopathogenetic implications remain unknown.

PMID- 12811578
TI  - Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein)
      on VEGF and IL-8 release from normal human keratinocytes stimulated with the
      proinflammatory cytokine TNFalpha.
AB  - In skin inflammation, vascular endothelial growth factor (VEGF) and IL-8 play an
      important role and are produced by activated keratinocytes. Recently, some
      polyphenols have been reported to exhibit antiinflammatory and antiangiogenic
      properties. We therefore evaluated the effects of green tea, its major component
      epigallocatechin-3-gallate (EGCG) and an isoflavone derived from soybean
      (genistein) on the release of VEGF and IL-8 by activated normal human
      keratinocytes (NHK). NHK cultured in defined medium were stimulated for 48 h with
      the proinflammatory cytokine TNFalpha with the addition or not of different
      concentrations of polyphenols. Levels of VEGF and IL-8 were measured in cell
      supernatants by enzyme-linked immunosorbent assays. The different constituents
      tested inhibited keratinocyte proliferation without inducing apoptosis. They
      reduced in a dose-dependent manner the basal release and the upregulation of VEGF
      in NHK. Green tea and EGCG were also potent inhibitors of IL-8 release by
      TNFalpha-stimulated NHK, whereas genistein exerted only minor effects. These
      results underline the divergent pathways involved in the downregulation of VEGF
      and IL-8 by polyphenols in activated keratinocytes. They also suggest that
      polyphenols may contribute to moderate inflammatory processes in skin diseases
      associated with angiogenesis.

PMID- 12811579
TI  - Antibacterial capacity of oral (epithelial) cells from healthy donors and
      patients with Behcet's disease.

PMID- 12811581
TI  - Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on
      fracture healing.
AB  - INTRODUCTION: Nonsteroidal antirheumatics (NSAR; NSAID) are often used in
      patients with fractured bones for analgetic reasons. This animal experiment was
      performed to determine the influence of NSAR on the process of fracture healing.
      As an alternative, tramadol, the centrally acting analgetic without peripheral
      effects, was included in this experiment. MATERIALS AND METHODS: Wistar rats were
      operated on by a transverse osteotomy of the proximal tibia of the left leg. The
      fracture was stabilized by intramedullary nailing (healing period 21 days). All
      drugs were applied orally twice a day. The animals were divided into four groups
      with 10 rats each: Group 1 was treated with placebo (P), group 2 with tramadol
      (T; 20 mg/kg body weight/day), group 3 with diclofenac sodium (DS; 5 mg/kg
      bw/day) for 7 days followed by 14 days of placebo, group 4 with diclofenac sodium
      (DL; 5 mg/kgbw/day) over 21 days. On day 21 the rats were killed, and each leg
      was examined by X-ray, then the tibia was examined by CT scan, three-point
      bending, and histology. RESULTS: The results of CT and three-point bending showed
      that rats treated by diclofenac presented with delayed fracture healing compared
      with those treated by placebo or tramadol. Bone density in CT was highest in
      group 1 (mean 611.4+/-50.1 mg/ml), followed by group 2 (mean 542.5+/-29.5 mg/ml).
      Groups 3 (mean 411+/-34.0 mg/ml; p=0.006) and 4 (mean 395.2+/-15.4 mg/ml;
      p=0.009) were significantly lower. The stability of the bones, as measured by the
      breaking force ( F(max)), was highest in group 1 (mean 45.8+/-19.0 N), followed
      by group 2 (mean 39.0+/-7.9 N; NS); group 3 (mean 20.6+/-7.8 N; p=0.01) was
      significantly lower than the placebo animals, followed by group 4 (mean 26.5+/
      8.3 N; p=0.03). Similar results were shown for bending stiffness: group 1 (mean
      1404.6+/-611.4 Nmm/mm), group 2 (mean 1033.2+/-232.1 Nmm/mm; NS), group 3 (mean
      564.2+/-457 Nmm/mm; p=0.045), and group 4 (mean 494.8+/-340.2 Nmm/mm; p=0.028).
      There were no significant differences between groups 1 and 2 and between groups 3
      and 4, respectively. Diclofenac serum levels on day 21 in rats with long-term
      diclofenac application (mean 301.4+/-83.3 ng/ml) were comparable to those in
      humans. CONCLUSION: Oral application of diclofenac significantly delayed fracture
      healing in rats. This effect might be comparable to other NSAR and fracture
      healing in humans.

PMID- 12811582
TI  - Characterization of newly established tumor lines from a spontaneous malignant
      schwannoma in F344 rats: nerve growth factor production, growth inhibition by
      transforming growth factor-beta1, and macrophage-like phenotype expression.
AB  - Transplantable tumor (KE) and clone cell (KE-F11) lines were established from a
      spontaneous malignant schwannoma found in an aged F344 rat. The primary tumor and
      KE tumors consisted of oval or spindle cells arranged in ill-defined bundles.
      Cultured KE-F11 cells exhibited polygonal or spindle configurations.
      Immunohistochemically, neoplastic cells in KE and KE-F11 reacted to vimentin, S
      100 protein, neuron-specific enolase, myelin basic protein, and glial fibrillary
      acidic protein in varying degrees, indicating neurogenic features; occasional
      cells reacted to alpha-smooth muscle actin. Cells positive for lysosomal enzymes
      (acid phosphatase and non-specific esterase), and ED1 (rat macrophage specific)
      were observed in KE-F11, and electron microscopically, cells with many lysosomes
      were frequently present, indicating expression of macrophage-like phenotypes.
      Bioassay analysis revealed that KE-F11 cells produced high levels of nerve growth
      factor. DNA synthesis was inhibited by addition of transforming growth factor
      beta1 (TGF-beta1), and Northern blot analysis revealed that expression of c-myc,
      a cell cycle-related immediate early gene, was depressed by TGF-beta1. Likely,
      TGF-beta1 is a factor capable of inhibiting cellular growth of Schwann cells.
      mRNA expression of the low-density lipoprotein receptor-related protein (LRP) was
      seen in KE-F11 cells by Northern blot analysis, and the level was decreased by
      lipopolysaccharide (LPS) treatment. LRP may be attributable to regulation of
      Schwann cell functions. KE-F11 cells seeded on laminin-coated dishes exhibited
      more extended cytoplasmic projections than on collagen type I-coated dishes. The
      present study provides evidence that biological properties of malignant
      schwannoma-derived cells might be affected by exogenous factors such as TGF
      beta1, LPS and laminin. These tumor lines may be useful for studies on
      pathobiological characteristics of Schwann cells.

PMID- 12811583
TI  - Reelin-immunoreactive Cajal-Retzius cells: the entorhinal cortex in normal aging
      and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a disorder of brain self organization associated with
      morphodysregulation at the synaptic level. Disturbances follow a hierarchical
      spatio-temporal pattern throughout the cortex and involve the re-activation of
      developmental molecular programs. The large glycoprotein reelin, synthesized by
      Cajal-Retzius (CR) cells, is an important component of a signaling pathway
      involved in embryonic development and modulation of synaptic circuitry, but is
      also implicated in the pathogenetic cascade in AD. Although the majority of CR
      cells sequentially disappears from the postnatal cortical layer I, a few of them
      persist in the normal adult brain. They continue to produce reelin, express a
      variety of other proteins, and are characterized by a typical morphology.
      Recently, CR cells have been reported to be altered in number and morphology in a
      variety of neurological and psychiatric diseases linked to maldevelopment. In the
      present study we show that reelin-positive CR cells persist in the layer I of the
      entorhinal cortex in normal senescent brains and are also preserved in AD. The
      majority of CR cells in AD is morphologically and cytochemically-as revealed by
      double labeling with calcium-binding proteins-indistinguishable from normal
      cases, suggesting that they are not dramatically altered in the entorhinal cortex
      of AD patients. Nevertheless, CR cells seem to be partially affected by the
      formation of paired helical filaments, indicating subtle changes that are
      suggested to be a result rather than a cause of the pathogenetic cascade of AD.

PMID- 12811584
TI  - Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the
      presence of glial cytoplasmic inclusions (GCIs), which are comprised of fibrils
      of the protein alpha-synuclein (alpha-syn). Increasing evidence indicate that the
      formation of these lesions leads to cellular dysfunction and degeneration. The
      events that result in the formation of GCIs remain poorly understood. It is
      possible that changes in the cytoplasmic milieu, perhaps the aberrant expression
      of alpha-syn-interacting proteins, can promote the polymerization of alpha-syn.
      The presence of the microtubule-binding protein, tau, in GCIs has been reported
      in some studies, but these findings have not been consistent, and these studies
      were performed prior to the availability of the more sensitive methods of
      detecting GCIs using anti-alpha-syn antibodies. Recently, 14-3-3 proteins,
      putative alpha-syn-interacting partners, have been reported in Lewy bodies, which
      also are pathological inclusions comprised of alpha-syn. In this study the
      presence of tau and 14-3-3 proteins in GCIs of 21 patients with MSA was
      investigated. For the majority of cases, tau and 14-3-3 proteins were detected
      only in a subset of GCIs. In some cases none of the GCIs contained 14-3-3 or tau.
      When present in GCIs, tau was in a hypophosphorylated state as demonstrated with
      phosphorylation-specific antibodies. Alpha-syn fibrillogenesis without 14-3-3 or
      tau appears to be sufficient for GCI formation, although it is possible that the
      accumulation of multi-functional proteins, like 14-3-3, in GCIs contribute to the
      disruption of cellular homeostasis.

PMID- 12811585
TI  - Active-site residue, domain and module swaps in modular polyketide synthases.
AB  - Sequence comparisons of multiple acyltransferase (AT) domains from modular
      polyketide synthases (PKSs) have highlighted a correlation between a short
      sequence motif and the nature of the extender unit selected. When this motif was
      specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora
      erythraea, the products included triketide lactones in which acetate extension
      units had been incorporated instead of propionate units at the predicted
      positions. We also describe a cassette system for convenient construction of
      hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and
      demonstrate its use in domain and module swaps.

PMID- 12811586
TI  - Oncostatin M, a multifunctional cytokine.
AB  - Oncostatin M (OSM) is a multifunctional cytokine that belongs to the Interleukin
      (IL)-6 subfamily. Among the family members, OSM is most closely related to
      leukemia inhibitory factor (LIF) and it in fact utilizes the LIF receptor in
      addition to its specific receptor in the human. While OSM was originally
      recognized by its unique activity to inhibit the proliferation of tumor cells,
      accumulating evidence now indicates that OSM exhibits many unique biological
      activities in inflammation, hematopoiesis, and development. Here, we review the
      profile of OSM activities, receptors, and signal transduction.

PMID- 12811587
TI  - Structure-function relationship in P-type ATPases--a biophysical approach.
AB  - P-type ATPases are a large family of membrane proteins that perform active ion
      transport across biological membranes. In these proteins the energy-providing ATP
      hydrolysis is coupled to ion-transport that builds up or maintains the
      electrochemical potential gradients of one or two ion species across the
      membrane. P-type ATPases are found in virtually all eukaryotic cells and also in
      bacteria, and they are transporters of a broad variety of ions. So far, a crystal
      structure with atomic resolution is available only for one species, the SR Ca
      ATPase. However, biochemical and biophysical studies provide an abundance of
      details on the function of this class of ion pumps. The aim of this review is to
      summarize the results of preferentially biophysical investigations of the three
      best-studied ion pumps, the Na,K-ATPase, the gastric H,K-ATPase, and the SR Ca
      ATPase, and to compare functional properties to recent structural insights with
      the aim of contributing to the understanding of their structure-function
      relationship.

PMID- 12811589
TI  - History and services of culture collections.
AB  - Microbial culture collections aim at collecting, maintaining and distributing
      microbial strains among microbiologists, and are considered to be a means to
      preserve microbial diversity ex situ. This article reviews the early history of
      culture collections, which were first set up in the late nineteenth century, with
      the introduction of pure culture techniques. It also describes the international
      connections between culture collections, which led to the foundation of the World
      Federation for Culture Collections (WFCC) and the International Congress of
      Culture Collections (ICCC). An overview of the Spanish Type Culture Collection
      (CECT) is included, as well as a description of the services that culture
      collections can offer.

PMID- 12811590
TI  - A brief history of the journal(s) of the SEM: staunchly resisting against
      improbability. II. From 1998 to 2002.

PMID- 12811591
TI  - Pyelonephritis caused by Actinobaculum schaalii in a child with pyeloureteral
      junction obstruction.
AB  - Reported here is the case of a 5-year old boy with a pyeloureteral junction (PUJ)
      obstruction and pyelonephritis caused by Actinobaculum schaalii, an Actinomyces
      like organism. Pyelonephritis or any other urinary tract infection caused by
      Actinobaculum schaalii has not been described in children before. The patient
      responded well to pyeloplasty in combination with antibiotic treatment.

PMID- 12811592
TI  - The genetics of chronic headaches.
AB  - Patients with chronic daily headaches (CDH) bear similarities to drug or
      substance abuse patients, for whom genetic liability loci have been implicated.
      We reviewed papers dealing with the metabolic and the genetic aspects of CDH. The
      relative risk for CDH in first-degree relatives is 2.1- to 3.9-fold increased
      compared to the general population. Genetic variation at the dopamine receptor 2
      has been associated with co-morbidity of migraine with aura with major depression
      and anxiety, and allele D of the angiotensin converting enzyme increases the
      frequency of migraine without aura attacks. In CDH, analgesic abuse was
      significantly associated with specific functional polymorphisms at the DRD 4 and
      at the dopamine transporter (DAT) genes, findings implicating dopamine-related
      genes in CDH with drug abuse. CDH carries a substantial genetic predisposition.
      Molecular genetic studies are, however, still few and preliminary.

PMID- 12811593
TI  - Neurophysiology of pain.
AB  - The transmission of pain-related information from the periphery to the cortex
      depends on signal integration at three levels of the nervous system: the spinal
      medulla, brainstem and telencephalon. In fulfilling its task of safeguarding
      human health, pain may develop as a result of damaged or altered primary afferent
      neurons (stimulus-dependent) or arise spontaneously without any apparent causal
      stimulus (stimulus-independent). Hyperalgesia (i.e. an exaggerated perception of
      pain after a painful stimulus) is due to an anomaly in the processing of
      nociceptive inputs in the central and peripheral nervous systems leading to the
      activation of the primary afferents by stimuli other than the usual stimuli.

PMID- 12811594
TI  - Neurogenic inflammation in primary headaches.
AB  - The headache in migraine is thought to result from neuronal nociceptive activity
      in the trigeminovascular system, that is, the meninges. In addition, trigeminal
      axons projecting to the meninges contain vasoactive neuropeptides, such as
      substance P, calcitonin gene-related peptide and neurokinin A, that may promote,
      when released, plasma protein leakage and vasodilation within dura mater,
      characteristic of neurogenic inflammation. Thus, it has been hypothesized that a
      sterile neurogenic inflammation in the meninges may be involved in generating or
      sustaining, via occurrence of a vicious cycle, the pain accompanying the migraine
      attacks. We here review the evidence in support of this hypothesis as well as its
      potential significance in better tailoring therapies in migraine or other types
      of primary headaches.

PMID- 12811595
TI  - Elusive amines and primary headaches: historical background and prospectives.
AB  - Although the role of trace amines such as tyramine, octopamine and synephrine in
      the pathogenesis of migraine has been debated for decades, this issue remains
      still unresolved. In spite of a relevant body of work, the inability to
      demonstrate specific receptors for these compounds and the lack of sensitive non
      radioactive methods for the detection of trace amines in biological samples have
      limited their investigation in humans. However, the recent identification of a
      new, large family of G protein-coupled receptors, some of which bind and are
      activated by trace amines, has focused renewed attention on these compounds. This
      discovery, together with the possibility of providing novel insights for
      evaluation of the pathophysiological role of trace amines in primary headaches,
      may offer new opportunities for pharmacological strategies acting on these
      receptors. In light of the new scientific background, this review outlines a
      historical perspective and summarizes evidence supporting a role of trace amines
      in the pathogenesis of migraine and cluster headache.

PMID- 12811596
TI  - Chronic pain-autonomic interactions.
AB  - The nociceptive and the autonomic nervous systems interact at the levels of the
      periphery, spinal cord, brainstem, and forebrain. Spinal and visceral afferents
      provide converging information to spinothalamic neurons in the dorsal horn and to
      neurons of the nucleus tractus solitarius and parabrachial nuclei. These
      structures project to areas involved in reflex, homeostatic and behavioral
      control of autonomic outflow and nociception. Clinical and experimental
      observations on migraine suggest that a general hyperexcitability could develop
      along nociceptive trigeminal neurons allowing the activation of descending
      pathways that facilitate pain processing or the suppression of pathways that slow
      down pain transmission. Slowly progressive dysfunction of central pain systems
      secondary to the repetition of attacks of the originating headache has been
      implicated in transforming the process from an episodic to a chronic condition.
      This concept of an irritable focus in the central nervous system is currently
      known as "central sensitization" and is a characteristic feature of visceral
      pain. Considering primary headache as the result of the interactions between the
      nociceptive and autonomic systems (visceral pain) can help us to understand the
      complex pathophysiology of these disorders and to explore new treatments.

PMID- 12811597
TI  - Psychological and emotional aspects and pain.
AB  - A patient's psychological condition can be influenced by symptoms and, at the
      same time, it can influence the perception of symptoms. In psychological
      assessment, pain can modify the results of a questionnaire, so a patient's state
      at the moment of the evaluation should be taken into account. Questionnaires used
      in assessment do not always provide clear-cut answers concerning the individual
      psychological component. Moreover, difficulties in classifying headache patients
      does not permit correct comparisons between population samples whenever patients
      are not classified into well defined homogeneous groups. Overall, in the three
      groups examined - migraine, tension-type headache and cluster headache - it can
      be affirmed that with self-report assessment based on questionnaires, the tension
      type headache subjects present a more interesting psychological profile for its
      clinical implications.

PMID- 12811598
TI  - Pain perception, brain and consciousness.
AB  - The brain-mind debate presents two principal streams of thought: materialist
      (brain and mind are different aspects of the same extremely complex "thing") and
      dualist (brain and mind are two independent things). Originating as a signal of
      damage transmitted to the thalamus, a warning message becomes perceived pain when
      the thalamus sends it to, and it is integrated by, the cerebral and cingulated
      cortices. In addition to various endogenous and exogenous physical factors that
      may affect (or even inhibit) the perception of pain, pain perception may be
      modulated, that is, enhanced or inhibited, by cognitive and emotive factors whose
      origins and existence are principal elements in the brain-mind debate. Studying
      the perception and modulation of pain provides an excellent heuristic model for
      studying the brain-mind debate and, in turn, an understanding of the brain-mind
      debate may offer new possibilities in pain therapy.

PMID- 12811599
TI  - Behavioral treatment approaches to chronic headache.
AB  - Over 3 decades of research have shown the utility of a number of behavioral
      treatments, chiefly relaxation, biofeedback, and cognitive behavior therapy, for
      uncomplicated forms of migraine and tension-type headache. However, the
      literature base is much less extensive for chronic, complicated, and refractory
      forms of headache. This paper reviews extant work on the usefulness of behavioral
      treatment for headache accompanied by medication overuse; chronic, daily, high
      intensity headache; refractory headaches; cluster headache; chronic tension-type
      headache; posttraumatic headache; and headache accompanied by psychiatric
      comorbidity. It concludes with a discussion of the role of environmental and
      familial factors in influencing chronic headaches. Suggestions for future
      research are pointed out along the way.

PMID- 12811600
TI  - International Headache Society classification: new proposals about chronic
      headache.
AB  - In the International Headache Society (IHS) classification of 1988, chronic daily
      headache (CDH) forms are not exhaustively categorized. The forthcoming revision
      of the classification will include a number of CDH forms that had been reported
      prior to 1988 or have been identified after that date. In particular, chronic
      migraine will be added to the classification as a complication of migraine,
      provided that use of symptomatic drugs does not exceed 10 days per month. In
      addition to chronic cluster headache and chronic paroxysmal hemicrania, short
      lasting unilateral neuralgiform headache with conjunctival injection and tearing
      (SUNCT) and hemicrania continua will be comprised among CDH forms with short
      lived attacks. Hypnic headache will be included in Group 4 ("Other primary
      headaches"). No additions will be made to the new IHS classification for forms
      such as new daily persistent headache (NDPH) and cervicogenic headache as
      proposed by Sjaastad.

PMID- 12811601
TI  - Chronic migraine and chronic tension-type headache: different aspects of the
      chronic daily headache spectrum. Clinical and pathogenetic considerations.
AB  - Clinicians working in the field of headache face great difficulty in managing
      patients with daily headache. Many of these patients have a history of episodic
      migraine that over several years has transformed into a chronic headache. Others
      have a history of episodic tension-type headache that also has chronicized. Still
      others present clinical characteristics that resemble both headache forms. In
      this article, we review the clinical and pathophysiological aspects of chronic
      daily headache and discuss the problems associated with its diagnosis.

PMID- 12811602
TI  - Neurobiology of chronic migraine.
AB  - Chronic daily headache (CDH) is an important problem for clinicians. It is
      frequent in tertiary care structures, although at present there is no clear
      consensus about definitions and operational criteria. In fact, CDH is a group of
      headache disorders that includes chronic migraine (CM). CDH usually evolves from
      an episodic headache form, which was migraine in most cases. Several
      psychopathological factors (e.g. psychiatric comorbidity, personality traits or
      stressful life events) and some somatic disorders (e.g. like arterial
      hypertension, allergic condition, sleep disturbances) are frequent in CM
      patients. Caffeine consumption, alcohol overuse and medication overuse (abortive
      drugs for migraine) could favour chronicity. The possible role of these factors
      remains poorly understood. Prospective studies and research about the
      pathophysiology of chronic pain will lead to a better understanding of CM.

PMID- 12811603
TI  - Quality of life and disability in primary chronic daily headaches.
AB  - We assessed functional disability and health-related quality of life (HRQOL) in
      Italian patients suffering from chronic migraine and medication overuse (150
      subjects) or chronic cluster headache (22 subjects). We used the validated
      Italian versions of the Migraine Disability Assessment Score (MIDAS) and of the
      Short Form 36 (SF-36). Patients with both conditions were characterised by
      significantly lower scores on most SF-36 scales than Italian normative data
      (Student's t test with Bonferroni correction). MIDAS scores revealed that
      patients had severe limitations in their ability to function, with high
      proportions forced to stop work and non-work activities, or experiencing
      significantly reduced productivity in all activity domains. These findings show
      that primary chronic headaches have a marked negative influence on patients'
      lives, compromising their sense of well being and their ability to function in
      different roles. We also found that MIDAS and SF-36 were sensitive to clinical
      changes in a group of 84 patients with chronic migraine and medication overuse
      who completed the both questionnaires before and after treatment.

PMID- 12811604
TI  - Chronic short-lasting headaches: clinical features and differential diagnosis.
AB  - Chronic short-lasting headaches are relatively rare, poorly recognized syndromes.
      The chronic short-lasting headaches are a group of chronic disorders in which the
      headaches occur for one year or more, either without remission or with remission
      periods less than two weeks; each attack lasts less than 4 hours. These headache
      syndromes are divided into those with autonomic activation and those without
      autonomic activation. This article presents the clinical features and
      differential diagnosis of the relatively rare and clinically challenging
      trigeminal autonomic cephalgias (TACs). The article also focuses on the clinical
      features and differential diagnosis of hypnic headache, a chronic shortlasting,
      non-unilateral headache of moderate intensity in which there is no autonomic
      involvement, in order to differentiate this from chronic cluster headache, with
      which it is often confused.

PMID- 12811605
TI  - The patient with medication overuse: clinical management problems.
AB  - Patients with chronic headache arise many problems in clinical management, often
      strictly related to medication overuse. IHS classification did not clear the
      different clinical presentation and a chapter dedicated to this problem is
      lacking. This condition is very frequently associated with psychiatric illness,
      so that the clinical features become more complex over the years. Most of
      patients share a past clinical condition of episodic migraine; this aspect is
      very important facing the therapeutical phase, because after discontinuing
      medication overuse, if present, the treatment must be direct toward this disease.
      To treat a patient with analgesic, or ergotamine, or triptan abuse, require much
      caution because stopping the drug may arise new problems, such as different
      headache, abstinence syndrome, epileptic seizures etc. We review the different
      possibility that we have to manage the overuser patient.

PMID- 12811606
TI  - Chronic headache in young patients: clinical aspects and treatment suggestions.
AB  - The term "chronic daily headache" (CDH) is used to describe a patient who suffers
      from recurrent headache, at an average frequency of 15 days per month without an
      underlying serious medical condition. CDH, sometimes referred to as chronic non
      progressive headache, was described in adults by Mathew et al. in 1987.
      Estimating the incidence and prevalence of this disorder has been difficult,
      because universally agreed criteria regarding the classification of CDH in
      children and adolescents have not been reached. This condition is a source of
      concern and disability both for the patient as well as their family. CDH may be
      associated with comorbid anxiety or depression, resulting in a tremendous amount
      of dysfunction for the youngster and the family.

PMID- 12811607
TI  - The role of the pain therapist in the approach to chronic headache.
AB  - Chronic daily headache (CDH) represents, for the anesthesiologists, a big match
      in the management of a pain which is simultaneously central and periferic, of a
      pain wich is psychical and disabiliting. This is a pain conducting the patient to
      overuse analgesic medicaments even making worse "allodynia" and the organic
      integrity. That's why a multidisciplinary approach to this kind of chronic benign
      pathology permits to improve prognosis and quality of life.

PMID- 12811608
TI  - Hemicrania continua: clinical and nosographic update.
AB  - Hemicrania continua (HC) is an uncommon primary headache syndrome. The main
      features of HC are: (i) strict unilaterality of the pain (moderate, fluctuating,
      relatively long-lasting); and (ii) absolute response to indomethacin. These two
      features may reflect the most reliable characteristics of the syndrome. Autonomic
      symptoms are not as prominent in HC as they are in cluster headache and chronic
      paroxysmal hemicrania, although they may exist. HC will be addressed in the 2003
      revision of the International Headache Society (IHS). In this paper we review the
      clinical features, classification and treatment of HC.

PMID- 12811609
TI  - Prevalence of primary headaches in Italian elderly: preliminary data from the
      Zabut Aging Project.
AB  - We describe preliminary 1-year prevalence data of recurrent migraine headache
      (MH), tension-type headache (TTH), and other headaches (OH) in a rural elderly
      population. A door-to-door two-phase survey was conducted on all elderly (>or=65
      years) residents of a rural village in southern Italy. Participants underwent a
      two-phase screening including a validated semi-structured questionnaire for
      headaches based on the International Headache Society criteria, and a
      neurological evaluation. Recurrent headache was defined as 3 or more attacks
      within the past 12 months. Out of 1031 participants evaluated, 225 (21.8%)
      suffered from recurrent headaches. One-year prevalence rates for headaches were
      respectively 4.6% for MH, 16% for TTH, and 1.3% for OH. For MH and TTH, but not
      for OH, prevalence rates were significantly higher for women than for men. Only
      MH prevalence rates significantly decrease with increasing age. In our
      population, about one-fifth of elderly subjects suffered from recurrent primary
      headaches. Prevalence rates were higher in women, and tended to decline with
      increasing age.

PMID- 12811610
TI  - Treatment of chronic daily headache with medication overuse.
AB  - Clinicians long have suspected that symptomatic medications taken by those with
      headache can cause rebound or drug-induced headaches if overused. This problem
      has been considered in the classification of headache disorders made by the
      International Headache Society. Patients who overuse medication must be withdrawn
      before their headache can be treated effectively. Sustained improvement following
      treatment for drug-induced headache can be difficult to achieve and at the moment
      there is no consensus on what approach may be more effective, in particular
      regarding outpatient or inpatient treatment withdrawal strategy. Clinical aspects
      and different therapeutic strategies for chronic daily headache patients with
      medication overuse are considered.

PMID- 12811611
TI  - Antiepileptic drugs in the treatment of chronic headaches.
AB  - In recent years, anticonvulsant drugs (AEDs) have been considered promising drugs
      in the prevention of migraine and other forms of headache, based on their action
      on the metabolism of gamma-aminobutyric acid (GABA) and glutamate. To date many
      AEDs are being evaluated for headache preventive treatment. The results are often
      encouraging even if not conclusive except for valproate, which has been
      extensively investigated and has been found to be effective and well tolerated in
      the preventive therapy of migraine. Other AEDs seem to be important in the
      treatment of patients with resistant headaches, with both migraine and epilepsy
      comorbid with mood and anxiety disorders or in neuropathic pain syndromes.

PMID- 12811612
TI  - Neuropathic cranial pain.
AB  - Neuropathic cranial pain, i.e. pain due to central or peripheral nervous system
      damage localized in cranial area, is a clinical challenge for the neurologist.
      Despite major advances in knowledge of physiology and biochemistry of pain,
      relief for many patients suffering from neuropathic pain remains incomplete.
      Adjuvant analgesics play a key role in the management of neuropathic pain. The
      introduction in the therapeutical armamentarium of antiepileptic drugs and the
      results derived from clinical studies indicate that some of these compounds show
      promise in the treatment of neuropathic pain.

PMID- 12811613
TI  - Non-pharmacological approaches to chronic headaches: transcutaneous electrical
      nerve stimulation, lasertherapy and acupuncture in transformed migraine
      treatment.
AB  - In an open, randomized trial, we evaluated transcutaneous electrical nerve
      stimulation (TENS), infrared lasertherapy and acupuncture in the treatment of
      transformed migraine, over a 4-month period free of prophylactic drugs. Sixty
      women suffering from transformed migraine were assigned, after a one month run-in
      period, to three different treatments: TENS (Group T; n=20), infrared
      lasertherapy (Group L; n=20) or acupuncture (Group A; n=20). In each group the
      patients underwent ten sessions of treatment and monthly control visits. In Group
      T patients were treated for two weeks (5 days/week) simultaneously with three
      TENS units with different stimulation parameters (I: pulse rate = 80 Hz, pulse
      width = 120 micros; II: 120 Hz, 90 micros; III: 4 Hz, 200 micros). In Group L an
      infrared diode laser (27 mW, 904 nm) was applied every other day on tender scalp
      spots. In Group A acupuncture was carried out twice a week in the first two weeks
      and weekly in the next 6 weeks. A basic formula (LR3, SP6, LI4, GB20, GV20 and Ex
      HN5) was always employed; additional points were selected according to each
      patient's symptomatology. The number of days with headache per month
      significantly decreased during treatment in all groups. The response in the
      groups differed over time, probably due to the different timing of applications
      of the three methods. TENS, lasertherapy and acupuncture proved to be effective
      in reducing the frequency of headache attacks. Acupuncture showed the best
      effectiveness over time.

PMID- 12811614
TI  - Hypothalamic deep brain stimulation for intractable chronic cluster headache: a 3
      year follow-up.
AB  - Cluster headache is the most severe among primary headaches. Positron emission
      tomography and functional MRI studies have demonstrated that the ipsilateral
      posterior hypothalamus is activated during cluster headache attacks and is
      structurally asymmetric in these patients thus indicating that cluster headache
      may originate at that level. These hypothalamic abnormalities in cluster headache
      led to the suggestion that deep brain stimulation of ipsilateral posterior
      inferior hypothalamus might produce clinical improvement in otherwise treatment
      refractory chronic cluster headache patients. In a patient with severe
      intractable chronic cluster headache, hypothalamic electrical stimulation
      produced complete and long-term pain relief with no relevant side effects. So far
      other operations have been performed and the results are encouraging in terms of
      both pain relief and safety. The efficacy of hypothalamic electrical stimulation
      provides some hints into cluster headache pathophysiology.

PMID- 12811615
TI  - Pharmacogenomics: state of the research and perspectives in clinical application.
AB  - The person-to-person variability of drug response is a major problem in clinical
      practice and in drug development. It can lead to therapeutic failure or adverse
      drug reactions (ADRs) in individuals or subpopulation of patients. In addition to
      the high occurence of ADRs and the associated morbidity and mortality,
      substantial costs are incurred. Potential risk factors for drug inefficacy or
      toxicity include drug-drug interactions, the patient's age, renal and liver
      functions or other disease factors, and lifestyle variables such as smoking and
      alcohol consumption. In addition, it has become clear in recent years that
      genetic factors may also significantly modify drug responses or increase the risk
      for ADRs. Genetic variations in genes (polymorphisms) for drug-metabolizing
      enzymes, drug receptors, and drug transporters have been associated with
      individual variability in the efficacy and toxicity of drugs. It is now widely
      accepted that migraine is a polygenic and multifactorial disorders, thus
      considered to be a genetic complex disease. Genetic studies on migraine suggested
      a role of CACNA1A and DRD2 genes as susceptibility genes in this disorder.

PMID- 12811616
TI  - Concepts of migraine headache pathogenesis: insights into mechanisms of
      chronicity and new drug targets.
AB  - The pathophysiology of migraine is incompletely understood. Neurobiological and
      gene regulation studies and advanced brain imaging are providing new insights
      into migraine pathogenesis. Recent discoveries have shed light on the neuronal
      events mediating both the aura and the headache phases of migraine, identifying a
      cerebral cortical origin of migraine aura, susceptibility to attacks based on
      cortical hyperexcitability, and the trigeminovascular system and its central
      projections as the origin of headache. This review focuses on abnormal modulation
      of brain nociceptive systems leading to central sensitization that may explain
      prolonged headache of the migraine attack and shift of the migraine phenotype
      from episodic to chronic headache.

PMID- 12811618
TI  - STR polymorphisms of "forensic loci" in the northern Han Chinese population.
AB  - A preliminary Chinese DNA database has been constructed by the analysis of
      samples from 2,211 Han Chinese in Liaoyang City, northeast China. Thirteen
      autosomal tetranucleotide short tandem repeats (STRs) widely used in forensic
      identification were selected for the DNA profiling, together with the X-Y
      homologous gene Amelogenin for sex determination. Only one of the 13 autosomal
      loci showed significant deviation from Hardy-Weinberg equilibrium in the
      individuals genotyped. The cumulative discrimination power and power of exclusion
      of the 13 loci were greater than 0.999999999 and 0.9999888, respectively, giving
      an average match probability of 5.5 x 10(-15) for the population. Allelic
      distributions at the vWA, TH01, D13S317, and D16S539 loci differed from African
      Americans and US Caucasians, and more detailed population data at these four loci
      may be needed to ensure their applicability for forensic purposes in Chinese
      populations. Previously unreported alleles were detected at several loci (some at
      relatively high frequencies), suggesting the need for their inclusion in the
      reference allelic ladder to meet the practical standard of forensic profiling in
      certain Chinese ethnic sub-populations. The preliminary DNA database provides
      base-line information applicable to the construction of a National Index System
      for criminal DNA profiling in PR China.

PMID- 12811619
TI  - The suturing concept for laparoscopic mesh fixation in ventral and incisional
      hernias: preliminary results.
AB  - Having found existing techniques for treatment of incisional hernias
      unsatisfactory, we developed a new laparoscopic approach with a Parietex
      Composite mesh. This study shows the preliminary results in order to analyze the
      validity of the concept on efficacy and safety. Three trocars are needed for this
      procedure. Non-reabsorbable sutures are mandatory for closure of large defects to
      avoid having to ultimately extrude the mesh. Ten to 12 cardinal stitches are
      applied on the polyester side of the mesh. The mesh is anchored to the anterior
      abdominal wall by transabdominal non-reabsorbable sutures without the use of
      staples or tacks. One hundred twenty patients with ventral and incisional hernias
      were included in this study. Early and late complications are reported, showing
      lower rates of morbidity and no mortality. This technique is satisfactory on the
      technical front, and the results are as good, or better, than in other trials.

PMID- 12811620
TI  - Purification and biological characterization of halocin C8, a novel peptide
      antibiotic from Halobacterium strain AS7092.
AB  - Halocins are bacteriocin-like proteins or peptides produced by many species of
      the family Halobacteriaceae. Halocin C8, excreted by the Halobacterium strain
      AS7092, is a single 6.3-kDa polypeptide with an isoelectric point of 4.4, which
      is sensitive to proteinase K but not to trypsin. Halocin C8 is quite stable, as
      it can be desalted, boiled, frozen, subjected to organic solvents, and stored in
      culture supernatant at 4 degrees C or in dH(2)O at -20 degrees C for more than 1
      year without losing activity. The purification of this halocin was achieved by
      combination of tangential flow filtration (TFF), Sephadex G50 and DEAE-sepharose
      chromatography. The N-terminal amino acid sequence was also determined by Edman
      degradation. Halocin C8 appeared to have a very wide activity spectrum, including
      most haloarchaea and even some haloalkaliphilic rods. When a sensitive strain of
      Halorubrum saccharovorum was exposed to halocin C8, the treated cells swelled at
      the initial stage, the cell wall appeared to be nicked and the cytoplasm was then
      extruded out, and the whole cell was eventually completely lysed. These results
      indicate that halocin C8 is a novel microhalocin and its primary target might be
      located in the cell wall of the sensitive cells.

PMID- 12811622
TI  - Requisite roles of Runx2 and Cbfb in skeletal development.
AB  - Each Runx (runt-related gene) protein exerts a fundamental role in different cell
      lineages. Runx2 is essential for osteoblast differentiation and plays an
      important role in chondrocyte maturation. Runx2 determines the lineage of
      osteoblastic cells from multipotent mesenchymal cells, enhances osteoblast
      differentiation at an early stage, and inhibits osteoblast differentiation at a
      late stage. In addition, Runx2 is involved in the production of bone matrix
      proteins. Further, Runx2 is a positive regulator of chondrocyte maturation and is
      involved in vascular invasion into the cartilage. Core binding factor beta (Cbfb)
      is a cotranscription factor which forms a heterodimer with Runx proteins. Cbfb is
      required for the functions of Runx1 and Runx2. Thus, Runx2/Cbfb heterodimers play
      essential roles in skeletal development.

PMID- 12811621
TI  - Xylene monooxygenase, a membrane-spanning non-heme diiron enzyme that
      hydroxylates hydrocarbons via a substrate radical intermediate.
AB  - The non-heme diiron enzyme xylene monooxygenase (XylM) has been shown to
      hydroxylate hydrocarbons via a hydrogen abstraction-carbon radical recombination
      mechanism (oxygen rebound). Using the radical clock bicyclo[4.1.0]heptane
      (norcarane) in a whole-cell assay, and observing the ratio of rearranged 3
      (hydroxymethyl)cyclohexene and unrearranged 2-norcaranol products, the lifetime
      of the substrate radical was determined to be approximately 0.2 ns. The wild-type
      organism Pseudomonas putida mt-2 and two separate Escherichia coli clones
      expressing xylMA genes gave similar results. One clone produced the Pseudomonas
      putida mt-2 XylMA hydroxylase and the other produced Sphingomonas yanoikuyae B1
      XylMA hydroxylase. Clones were constructed by inserting genes for xylene
      monooxygenase and xylene monooxygenase reductase downstream from an IPTG
      inducible T7 promoter. Mechanistic investigations using whole-cell assays will
      facilitate more rapid screening of structure-function relationships and the
      identification of novel oxygenases. This approach should enable the construction
      of a picture of the key metalloenzymes and the mechanisms they use in selected
      parts of the global carbon cycle without requiring the isolation of every protein
      involved.

PMID- 12811623
TI  - Calcitonin for the treatment of osteoporosis: dosage and dosing interval in
      Japan.

PMID- 12811624
TI  - Interaction of AP-1 and the ctgf gene: a possible driver of chondrocyte
      hypertrophy in growth cartilage.
AB  - The expression of the connective tissue growth factor ( ctgf) gene increases
      along with the differentiation of growth cartilage cells, and the highest
      expression is observed in the hypertrophic stage. Similarly, recent reports
      demonstrated c- fos expression in chondrocytes in the early hypertrophic zone of
      growth cartilage, and suggested that the c- fos gene may play a crucial role in
      the regulation of hypertrophic differentiation. A chondrocytic human cell line,
      HCS-2/8, is known to retain a variety of chondrocytic phenotypes. When such cells
      were kept overconfluent, they expressed increasing levels of c- fos transcripts
      along a time course phenotypically similar to that of hypertrophic
      differentiation. Moreover, by using a competitive electromobility-shift assay, we
      found that AP-1, a Fos/Jun heterodimer, in HCS-2/8 was capable of binding not
      only to a typical AP-1-binding DNA fragment but also to the enhancer fragment of
      the ctgf gene. Based on the findings above, we hypothesize that, prior to
      hypertrophic differentiation, AP-1-related oncogenes are activated and that their
      gene products subsequently activate ctgf gene expression, which might eventually
      induce hypertrophy.

PMID- 12811625
TI  - Comparative effects of orchidectomy and sciatic neurectomy on cortical and
      cancellous bone in young growing rats.
AB  - The purpose of the present study was to compare the effects of orchidectomy and
      sciatic neurectomy on cortical and cancellous bone in male rats. Fifty male
      Sprague-Dawley rats, 6 weeks of age, were randomized into five groups, with ten
      rats in each group: baseline control, age-matched intact control, orchidectomy
      (ORX), unilateral sciatic neurectomy (NX), and ORX + NX. After 8 weeks of
      feeding, the tibial shaft and proximal tibia were processed for cortical and
      cancellous bone histomorphometric analyses, respectively. ORX-induced reductions
      in maturation-related cortical and cancellous bone gains were attributable to
      decreased periosteal bone gain and increased trabecular bone resorption,
      respectively. NX- and ORX + NX-induced reductions in maturation-related cortical
      bone gain were attributable to decreased periosteal bone formation and increased
      endocortical bone turnover, while NX- and ORX + NX -induced reductions in
      maturation-related cancellous bone gain were attributable to increased bone
      resorption and decreased bone formation. NX more markedly reduced maturation
      related cortical and cancellous bone gains than did ORX, and the ORX-induced
      reductions in maturation-related cortical and cancellous bone gains were more
      pronounced when combined with NX. The present study demonstrated differences in
      changes in cortical and cancellous bone following ORX and NX in young rats. The
      importance of mechanical loading, with or without testosterone deficiency, is
      emphasized in cortical and cancellous bone growth.

PMID- 12811626
TI  - Clinical usefulness of measurements of urinary deoxypyridinoline (DPD) in
      patients with postmenopausal osteoporosis receiving intermittent cyclical
      etidronate: advantage of free form of DPD over total DPD in predicting treatment
      efficacy.
AB  - Deoxypyridinoline (DPD) in urine, which reflects systemic bone resorption, is
      considered useful for assessing the effects of osteoporosis treatment. However,
      there are various methods of measuring DPD in urine but have been few comparative
      studies of the effectiveness of these methods. In this study, we investigated 94
      postmenopausal women (63 patients administered with intermittent cyclical
      etidronate (ICE), and 31 control patients) focusing on total DPD and free DPD,
      measured by high-performance liquid chromatography (HPLC) and enzyme-linked
      immunosorbent assay (ELISA), respectively. For other metabolic bone markers,
      i.e., tartrate-resistant acid phosphatase (TRAP), bone-specific alkaline
      phosphatase (BAP), and osteocalcin (OC), we also investigated the ability of
      these markers to predict increases in bone mineral density (BMD), by employing
      receiver operating characteristic (ROC) analysis in relation to increasing BMD
      following ICE therapy, and we determined the usefulness of the different
      metabolic bone markers, using the signal-noise ratio derived from the mean
      significant change (MSC), which is double the day-to-day coefficient of variation
      in healthy volunteers. In the same way, we defined a significant change in BMD as
      double the mean change in BMD for 6 months after the initiation of observation in
      the control group, and we used this value as the cutoff value for ROC analysis.
      It was found that the assessment of urinary DPD was useful for assessing the
      treatment efficacy of ICE, and the assessment of changes at week 12 of therapy
      was most effective. In order to recognize changes in metabolic bone markers when
      the MSC is considered as the cutoff value, it is useful to assess the change in
      total DPD by HPLC. However, in order to predict increases in BMD 6 months or more
      after the initiation of ICE, it seems more effective to measure free DPD by
      ELISA. We conclude, therefore, that the measurement of free DPD by ELISA is more
      useful, especially when treatment efficacy of ICE is clinically predicted in
      individual patients with osteoporosis.

PMID- 12811627
TI  - Association between bone loss and promoter polymorphism in the IL-6 gene in
      elderly Japanese women with hip fracture.
AB  - Recently, a G/C polymorphism was found at position -573 of the interleukin-6 ( IL
      6) gene promoter. We investigated how this genetic polymorphism relates to IL-6
      production and osteoporosis in elderly Japanese women. Genomic DNA was extracted
      from an aliquot of monocytes in the bone marrow; the monocytes were
      simultaneously used to form osteoclast-like multinucleated cells (MNCs) and to
      produce IL-6. Of the 47 subjects with fractures, 96% had a C allele at position 
      573 of the IL-6 gene. Only 2 subjects possessed homozygotes of G at that
      position. We investigated IL-6 levels, MNC formation in bone marrow culture, and
      femoral neck bone mineral density (BMD) in the subjects with the GC and CC
      genotypes. There were no significant differences between these genotypes as
      regards IL-6 levels, MNC formation, and femoral neck BMD. However, in the CC
      genotype, there was a negative relationship between femoral neck BMD and IL-6
      levels, and between femoral neck BMD and MNC formation, whereas in the GC
      genotype and combined (GC + CC) genotypes, femoral neck BMD tended to be related
      to IL-6 levels and MNC formation. Moreover, the stromal cells in the CC genotype
      showed higher IL-1alpha-stimulated IL-6 production than did the stromal cells in
      the GC genotype. Our findings suggest that important information might be
      obtained not only by continued comparison of different genotypes but also by
      comparative study within each particular genotype.

PMID- 12811628
TI  - Sequential changes in periprosthetic bone mineral density following total hip
      arthroplasty: a 3-year follow-up.
AB  - We sequentially measured the periprosthetic bone mineral density (BMD) of the
      femur after cementless total hip arthroplasty, using dual-energy X-ray
      absorptiometry, over a 3-year period. The periprosthetic bone was divided into
      three regions (proximo-medial, middle, and distal to the prosthetic stem). After
      the insertion of a fully porous coated stem in 21 patients, the BMD was measured
      within 3 weeks, and 6, 12, 24, and 36 months after surgery. At 6 months, all
      zones showed a decrease in BMD relative to the BMD within 3 weeks, but
      subsequently the BMD was unchanged. The lower the BMD within 3 weeks of surgery,
      or the lower the body weight, the higher the percent loss of BMD at 6 months.

PMID- 12811629
TI  - Influence of number of pregnancies on bone mineral density in postmenopausal
      women of different age groups.
AB  - As data on the relationship between parity and bone mineral density often seem to
      be controversial, ultimately, a comprehensive research study was thought to be
      necessary. This study focused on examining the influence of the number of
      pregnancies on bone mineral density and investigating the relationship between
      pregnancy and bone mineral density at four sites in postmenopausal women of
      different age groups. A total of 509 postmenopausal women, varying from 45 to 86
      years of age (mean age of 60.85 +/- 7.53 years) were considered for the study. A
      standardized interview was employed to obtain information on demographics,
      lifestyle, and, reproductive and menstrual histories. Patients were separated
      into four groups according to the number of pregnancies, i.e., nulliparae (52
      patients), one to two parity (66 patients), three to five parity (178 patients),
      and more than five parity (213 patients). The patients were further classified
      into two age groups, 40-59 years (233 patients) and 60-80 years (276 patients),
      respectively. The number of pregnancies was found to range from 0 to 17 (with an
      overall mean of 5.42 +/- 3.68), with 4.29 +/- 2.74 (range, 0-16) accounting for
      live births, while 1.02 +/- 1.53 (range, 0-14) were abortions. There were no
      significant differences among the groups with respect to parameters such as, age,
      body mass index (BMI), age at menarche, age at menopause, and years since
      menopause (P > 0.05) in all of the 509 women and in the 40- to 59- and 60- to 80
      year groups. When all the patients were considered, the bone mineral density
      (BMD) values of the spine and the trochanter for the more-than-five-parity group,
      were found to be significantly lower than those of the other groups (P < 0.05),
      while the BMD values of the spine and the femur (neck, trochanter) appeared to
      decrease with increasing parity. In the 40- to 59-year group, the BMD of the
      spine in both the nulliparae and one-to-two-parity groups was significantly
      higher than that of the more-than-five-parity group (P < 0.05). No significant
      differences were found among the groups with respect to the BMD values at any
      femur sites. The nulliparae patients in the 60- to 80-year group exhibited
      significantly higher trochanter and Ward's BMD values than those of the more-than
      five-parity group (P < 0.05), whereas in the one-to-two-parity group, spine BMD
      values appeared to be significantly higher than those of the more-than-five
      parity group (p < 0.05). Significant correlations were found between the number
      of pregnancies and BMD values for the spine (r = -0.23; P < 0.01), trochanter (r
      = -0.16; P < 0.01), and Ward's triangle (r = -0.14; P < 0.05), with no
      significant correlation for femur neck BMD (r = -0.08; P > 0.05) values. In
      conclusion, the present study suggests that the number of pregnancies has an
      effect on the BMD values and that this situation shows a variation in different
      age groups. In addition, our study indicates that there is a significant
      correlation between the number of pregnancies and the spine, trochanter, and
      Ward's triangle BMD, but there is no correlation for the femur neck BMD.

PMID- 12811630
TI  - Should COPD patients be routinely evaluated for bone mineral density?
AB  - There are many factors that increase the risk of osteoporosis, including smoking,
      malnutrition, vitamin D deficiency, hypogonadism, limited physical activity due
      to chronic disease, and corticosteroid therapy in chronic obstructive pulmonary
      disease (COPD). The aim of this study was to investigate bone mineral density
      (BMD) in COPD outpatients receiving regular therapy in order to clarify whether
      they were suitable candidates for bone mass screening. Twenty-eight male,
      clinically stable COPD patients (mean age, 63 +/- 9 years) and 20 male volunteer
      subjects with normal pulmonary function, as a control group (mean age, 63 +/- 5
      years) were admitted to the study. The BMD of the COPD patients and control
      subjects was measured by dual X-ray absorptiometry (Hologic QDR-4000). Pulmonary
      function tests and arterial blood gas analyses of COPD patients revealed moderate
      degree airway obstruction with mild hypoxemia and normal pH. Rates of 42% and 67%
      for lumbar and femoral osteopenia, respectively, and 35%, and 10% for lumbar and
      femoral osteoporosis, respectively, were detected in the COPD patients; whereas
      the rates of lumbar and femoral osteopenia were 40% and 50%, respectively, and
      the rates of lumbar and femoral osteoporosis were 40% and 15%, respectively, in
      the control subjects. There was no statistically significant difference between
      the BMD values of the COPD and control groups. Lumbar BMD was 0.871 g/cm(2) in
      the COPD patients and 0.853 g/cm(2) in the control group (P = 0.682); femoral BMD
      was 0.790 g/cm(2) in the COPD patients and 0.795 g/cm(2) in the control group (P
      = 0.909). Bone density was correlated with the degree of airway obstruction and
      arterial blood pH. In conclusion, the BMD values of COPD patients were not
      different from those of control subjects of the same age group. We conclude that
      the risk of osteoporosis is not increased in appropriately treated patients with
      moderate-degree COPD, and there is no indication for bone mass screening in this
      group.

PMID- 12811631
TI  - Low serum levels of intact osteocalcin in patients with congestive heart failure.
AB  - Impaired bone metabolism is a frequent complication following heart
      transplantation. Little is known, however, about possible alterations in bone
      turnover of pretransplant patients with congestive heart failure (CHF). We
      therefore studied biomarkers of bone turnover in 21 male patients with CHF (New
      York Heart Association [NYHA] classification > II) compared with 21 controls
      (NYHA classification < II). Biomarkers of bone formation (intact osteocalcin and
      carboxy-terminal propeptide of type I collagen), markers of bone resorption (N
      telopeptide and C-telopeptide of type I collagen), undercarboxylated osteocalcin
      (an indicator of fracture risk), and concentrations of calcium, parathyroid
      hormone, and vitamin D metabolites (25-hydroxyvitamin D and calcitriol) were
      measured in fasting blood samples. Serum levels of intact osteocalcin were 44.5%
      lower (P < 0.01), and the ratio of undercarboxylated-to-intact osteocalcin was
      113% higher (P < 0.01) in the patients in comparison with the controls. Moreover,
      patients had 34% lower 25-hydroxyvitamin D levels (P < 0.01) and 22% lower
      calcitriol levels (P < 0.05) than the controls. The bone resorption markers, N
      telopeptide and C-telopeptide; the bone formation marker, carboxy-terminal
      propeptide of type I collagen; parathyroid hormone levels; and albumin-adjusted
      serum calcium concentrations did not differ between patients and controls (all P
      values > 0.05). In summary, there were no biochemical signs of enhanced bone
      collagen resorption in pretransplant CHF patients. However, the low serum levels
      of intact osteocalcin and the high ratio of undercarboxylated-to-intact
      osteocalcin deserve further consideration.

PMID- 12811632
TI  - Is the Ecstasy-induced ipsilateral rotation in 6-hydroxydopamine unilaterally
      lesioned rats dopamine independent?
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) has recently been hypothesized to be
      effective against the symptoms of Parkinson's disease. Therefore we tested the
      effects of MDMA-derivatives in the rotational behavioural model. Male Sprague
      Dawley rats were lesioned unilaterally with 6-hydroxydopamine at the medial
      forebrain bundle. MDMA was administered at doses of 2.5, 5.0 and 10.0 mg/kg, its
      derivatives N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butananamine (MBDB), 3,4
      Methylenedioxy-N-ethylamphetamine (MDE) and 3,4-Methylenedioxyamphetamine (MDA)
      at 5.0 mg/kg respectively. All substances induced ipsilateral rotations, MDA
      being the most effective. MDMA induced rotations were attenuated by the selective
      serotonin reuptake inhibitor Citalopram but were only slightly reduced by pre
      treatment with the selective serotonin synthesis inhibitor PCPA (para
      chlorophenylalanine). The effects of MDMA can therefore not fully be explained by
      serotonin release or by dopaminergic activity of the drugs.

PMID- 12811633
TI  - Pronounced arterial collateralization was induced after permanent rat cerebral
      four-vessel occlusion. Relation to neuropathology and capillary ultrastructure.
AB  - The present study investigates chronic changes in cerebral arterial vessel
      system, microvasculature, and brain histopathology using an adult rat model based
      on permanent and stepwise occlusion of four cerebral vessels. Digital subtraction
      angiography (DSA) was performed to study chronic changes in arterial cerebral
      vessel system after permanent vessel occlusion. Long-lasting functional changes
      such as NMDA-, AMPA- and GABA(A)-receptor binding were detected in hippocampus
      and dentate gyrus using autoradiography. Structural changes in cerebral
      capillaries were investigated using light- and electron microscopy. Chronic
      cerebral oligemia did not cause any significant changes in the densities of
      excitatory glutamate and inhibitory GABA(A) receptors. By electron microscopy we
      could document, however, that most capillaries in vessel-occluded animals shrank,
      the endothelial cells were prominent with enlarged nuclei and increased
      cytoplasm, and the basal membrane was thickened. In contrast to the degenerative
      changes in brain capillaries, pronounced arterial collateralization was disclosed
      by DSA after chronic brain vessel occlusion. The model of chronic occlusion of
      four cerebral vessels is characterized by capillary degeneration and arterial
      collateralization proceeding in parallel. Thus, this rat model may be useful in
      investigations of long-lasting compensatory mechanisms contributing to
      cerebrovascular or neurodegenerative disorders.

PMID- 12811634
TI  - The pedunculopontine nucleus projection to the parafascicular nucleus of the
      thalamus: an electrophysiological investigation in the rat.
AB  - Extracellular electrophysiological recordings of neurons of the parafascicular
      nucleus of the thalamus were done in normal rats and in rats bearing lesions of
      either the cerebellar nuclei or the entopeduncular nucleus to investigate the
      functional control of the pedunculopontine nucleus on the parafascicular nucleus.
      A total of 97 neurons were recorded in the parafascicular nucleus in intact rats,
      83 in rats bearing a chronic electrolytic lesion of the ipsilateral deep
      cerebellar nuclei, and 69 in rats bearing an ibotenate lesion of the ipsilateral
      entopeduncular nucleus. Lesions of the cerebellar nuclei or the entopeduncular
      nucleus were made to evaluate the participation of cerebellothalamic fibers or of
      polysynaptic basal ganglia circuits in the responses recorded in parafascicular
      neurons following electrical microstimulation of the ipsilateral pedunculopontine
      nucleus. Two types of excitation and one type of inhibition were the main
      responses observed in neurons of the parafascicular nucleus following stimulation
      of the pedunculopontine nucleus. The first type of excitation, observed in 49.5%
      of neurons recorded in normal rats, had an onset of 1.8 +/- 0.6 ms, lasted 9.2 +/
      0.8 ms and was able to follow high frequency stimulation over 300 Hz. The second
      type of excitation, observed in a smaller percentage of neurons recorded (3.1%),
      was a long-latency (8.3 +/- 0.7 ms) activation lasting 19.0 +/- 4.5 ms. It did
      not follow stimulation frequencies higher than 50-100 Hz. The inhibitory response
      was observed in 17.5% of the neurons recorded. The latency of this inhibition was
      4.5 +/- 1.8 ms and the duration 41.9 +/- 6.8 ms. In rats bearing a lesion of the
      deep cerebellar nuclei or of the entopeduncular nucleus, the short-latency
      activation was still present in 24.1% and 31.9% of neurons recorded,
      respectively. However, the occurrence of the long-latency excitation rats bearing
      lesions of either the cerebellum or the entopeduncular nucleus increased to 12.1%
      and to 17.4%, respectively, while the occurrence of the inhibition rose to 22.9%
      and to 28.9%. These results show that an excitatory influence on the
      parafascicular nucleus is exerted by the pedunculopontine nucleus irrespectively
      of the presence of cerebellofugal fibers. This influence appears to be also
      independent from the integrity of basal ganglia circuits having a relay at the
      level of the entopeduncular nucleus. However, the variety of responses recorded
      suggests that the influences of the pedunculopontine nucleus on the
      parafascicular nucleus are by far more complex than those exerted on its basal
      ganglia targets such as the substantia nigra. The results are discussed according
      to a model of functioning of pedunculopontine fibers directed to thalamic and
      basal ganglia nuclei.

PMID- 12811635
TI  - Modulation of disease risk according to a cathepsin D / apolipoprotein E genotype
      in Parkinson's disease.
AB  - Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the
      pathogenesis of sporadic Alzheimer's disease (AD) due to interference with
      protein degradation mechanisms. A C224T (A38V) polymorphism in exon 2 of the CTSD
      gene is reported to be associated with an increased risk for AD. The partially
      overlapping pathology between AD and Parkinson's disease (PD) led us to
      investigate the role of this polymorphism in PD. Using association studies in 457
      German PD patients and 340 controls we found no evidence for direct association
      between the CTSD genotype and PD. However, stratification for the apolipoprotein
      E (APOE) epsilon4 allele suggests a protective effect of the CTSD T-allele in PD
      (OR = 0.24, p = 0.002). Our findings suggest interference of CTSD and APOE
      polymorphisms in the pathogenesis of PD, in the sense of modulating disease risk.

PMID- 12811636
TI  - Dopaminergic contributions to the visual categorization of natural scenes:
      evidence from Parkinson's disease.
AB  - Recent evidence raised the possibility that dopaminergic mechanisms in the
      neostriatum play an important role in categorization. In this study, we examined
      the electrophysiological correlates of natural scene categorization in
      Parkinson's disease (PD), which is characterized by the depletion of dopamine in
      the neostriatum. Event-related potentials (ERPs) were recorded in PD patients and
      age-matched control subjects using a natural scene categorization task. Subjects
      had to decide whether a briefly presented image contained animals or non-animals.
      In the control group, the mean amplitudes of N1 (150-250 ms) and N2 components
      (400-600 ms) were more negative for non-animal scenes as compared with stimuli
      containing animals, whereas P2 (250-350 ms) was more positive for animals. In
      contrast, in the PD group the mean amplitudes of N1 and N2 components were
      similar for both animal and non-animal stimuli, and the P2 amplitudes were
      reduced. In the case of N1 peak latency, there was no between-group difference,
      whereas the N2 and P2 components were significantly delayed in the PD group.
      These results suggest that both perceptual (N1) and semantic (N2) processes
      related to the categorization of natural scenes are specifically impaired in PD.
      In the temporal domain, the slowed semantic processing is preceded by a
      relatively normally paced perceptual analysis. These findings are in agreement
      with the hypothesis emphasizing the importance of striatal dopaminergic
      mechanisms in classification functions.

PMID- 12811637
TI  - Prevalence of vascular lesions in dementia with Lewy bodies. A postmortem study.
AB  - The frequency of vascular lesions in dementia with Lewy bodies (DLB) has been
      suggested to be less common than for Parkinson disease (PD), but exact data on
      the relationship between DLB and stroke are not available. 387 consecutive cases
      of autopsy-proven Lewy body disease - 291 cases of idiopathic PD (Lewy body
      disease of brainstem type) and 96 cases of DLB - and 390 age-matched controls
      were compared using current routine stains and immunohistological methods. The
      frequency of cerebrovascular lesions of various intensity (lacunes, amyloid
      angiopathy, old ischemic infarcts and hemorrhages) was lower in DLB than in both
      PD and controls (34.4% vs. 36.7% and 33.3%) (p > 0.03). While acute ischemic
      strokes and hemorrhages were rarely present in both PD and controls (4.1 vs.
      3.3%), no such lesions were observed in DLB. At variance to previous findings in
      autopsy-proven PD and Alzheimer disease (AD), these data suggest a protective
      effect against stroke and no greater susceptibility to death from stroke in the
      DLB population studied, but the reasons remain unclear. On the other hand, like
      in PD and AD, cognitive impairment in DLB appears to be independent from
      coexisting vascular pathology and is mainly related to neuritic Alzheimer
      pathology.

PMID- 12811638
TI  - [3H]GR113808 binding to serotonin 5-HT(4) receptors in the postmortem neocortex
      of Alzheimer disease: a clinicopathological study.
AB  - Abnormalities in neural transmission of serotonin (5-HT) may play a role in both
      cognitive and neuropsychiatric features of Alzheimer disease (AD). We measured 5
      HT(4) receptors in the postmortem frontal and temporal cortex of 34 AD subjects
      and 15 controls by radioligand binding with [3H]GR113808. Receptor binding data
      was then correlated with prospectively assessed cognitive (Mini-Mental State
      Examination, MMSE) and behavioral (Present Behavioural Examination, PBE) data.
      [3H]GR113808 binding affinity (K(D)) and density (B(max)) in AD were unchanged
      compared to controls in both cortical regions, and did not correlate with MMSE or
      PBE data. The binding parameters were also not related to disease duration,
      senile plaque and neurofibrillary tangle counts, and neuroleptic medication. We
      conclude that unlike other 5-HT receptors, 5-HT(4) receptor binding affinity and
      density do not seem to be affected in the frontal and temporal cortex in AD and
      may not have a direct role in the clinical features of the disease.

PMID- 12811639
TI  - Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's
      disease.
AB  - Both monoamine oxidase (MAO) A and MAO B in the brain have been implicated in the
      etiology of Alzheimer's disease. MAO B is elevated in plaque-associated glia in
      Alzheimer brain. Elevations in MAO A in Alzheimer neurons have been linked to
      increases in neurotoxic metabolites and neuron loss. We investigated the
      relationship between cognitive function in Alzheimer patients and post-mortem
      prefrontal cortex MAO A and B activities. Prefrontal cortex tissue from 92
      Alzheimer patients and 74 neurologically normal subjects was obtained at autopsy
      and analyzed for activities of MAO A and B by radioenzymatic methods. Mini Mental
      Status Exam was performed on Alzheimer patients within 1 year of death. Alzheimer
      brains were analyzed for Braak stage, tangles, plaques and choline
      acetyltransferase activity. Prefrontal cortex MAO B activity was significantly
      increased by 16% in Alzheimer patients versus normals, whereas MAO A activity was
      significantly decreased by 17% in these same patients. Neither MAO A nor MAO B
      activities correlated with cognitive function (MMSE score), choline
      acetyltransferase activity, plaques, neurofibrillary tangles, Braak stage, or age
      of disease onset in the Alzheimer patients. With increasing Alzheimer duration or
      increasing Braak stage, MMSE scores and choline acetyltransferase activity
      declined, but levels of MAO A and B in prefrontal cortex were unchanged. Patients
      in the upper quintile for MAO A or B activity did not differ significantly from
      those in the lowest quintile with respect to MMSE scores or age of Alzheimer
      disease onset. We conclude that the changes in MAO A and B in the prefrontal
      cortex occur very early in Alzheimer's disease and remain relatively constant as
      the disease progresses.

PMID- 12811640
TI  - GAD(67): the link between the GABA-deficit hypothesis and the dopaminergic- and
      glutamatergic theories of psychosis.
AB  - Decreases in the 67 kDa isoenzyme of brain glutamic acid decarboxylase (GAD(67))
      expression have been consistently found in patients with bipolar disorder and
      schizophrenia. In animals GAD(67) expression is diminished by chronic, but not
      acute stimulation of dopamine D(2) receptors and by short-term blockade of NMDA
      receptors. In contrast, chronic treatment with D(2) receptor antagonists enhances
      GAD(67) expression. Thus, antipsychotic treatment cannot explain the reduction in
      GAD(67) levels in patients with psychotic disorders. Rather, pathophysiological
      findings such as reduced viability of cortical glutamatergic neurones (in
      schizophrenia) or enhanced dopamine sensitivity (in bipolar disorder) might
      explain the observed reduction in GAD(67). Since reduction in GAD(67) expression
      leads to reduced levels of GABA, the GABAergic inhibitory control over
      glutamatergic cells is reduced. Psychosis could result from AMPA receptor
      activation caused by overactivity of the glutamatergic system. GAD(67) levels
      would thus be a surrogate marker for psychosis liability. Pharmacological
      principles that raise GAD(67) expression levels could represent novel targets for
      antipsychotic therapy.

PMID- 12811641
TI  - Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and
      treatment outcome in alcohol dependence.
AB  - The dopaminergic system is critically involved in reward mechanisms mediating the
      reinforcing effects of alcohol. The intention of this study was to investigate
      the genotypic frequencies of the -141C Ins/Del polymorphism of the DAD2 receptor
      gene as well as the Bal I polymorphism of the DAD3 receptor and their potential
      association with treatment outcome in alcoholism. Therefore, individuals
      suffering from primary alcohol dependence were clinically and genetically
      characterized and followed prospectively over a period of one year after
      inpatient treatment. No association was found between DAD2 or DAD3 receptor gene
      variants and treatment outcome as reflected by abstinence/relapse after one year.
      Taking into account potential stratification effects, such as family history,
      gender, age of onset, or severity of the disease an association with DAD2 or DAD3
      gene variants could neither be found. In conclusion, we found no evidence that
      the DAD2 or DAD3 gene variants investigated have a major influence on treatment
      outcome in primary alcohol dependence.

PMID- 12811642
TI  - Electrophysiological investigation of the effectiveness of methylphenidate in
      children with and without ADHD.
AB  - The Continuous Performance Test (CPT) is an appropriate instrument for assessment
      of correlates at the brain electrical activity level of attention and response to
      stimulant medication. The aim of the study was to confirm at the
      electrophysiological level the clinical effectiveness of methylphenidate (MPH) in
      children with attention deficit / hyperactivity disorder (ADHD); to this end, a
      comparative study of hyperactive and healthy control children was undertaken,
      employing a modified CPT test. Twenty-one channel ERPs from 17 hyperactive boys,
      with and without MPH treatment, and from 20 healthy control children were
      analyzed with reference-independent techniques. The resulting quasi-stabile
      microstates correspond to the time ranges of the conventional ERP components
      P100, P200 and P300 (with the subcomponents P3a and P3b) and could be
      discriminated by means of data-based segmentation. The P3a amplitudes of the
      hyperactive children, in each case with and without MPH medication, were compared
      with those of healthy controls. P3a segment amplitudes were significantly lower
      in non-medicated ADHD patients than in healthy children, both following positive
      and inhibitory stimulus conditions. A significant medication effect was detected
      following MPH treatment: segment 3 amplitudes in MPH-treated hyperactive children
      were not significantly different from those of healthy controls. MPH exerts a
      highly potent effect on stimulus recognition and resulting consequences.
      Application of the CPT-OX enables the reliable measurement of
      electrophysiological correlates of the clinical effectiveness of MPH under
      different stimulus conditions.

PMID- 12811643
TI  - Arbuscular mycorrhizal fungal propagules in a salt marsh.
AB  - The tolerance of indigenous arbuscular mycorrhizal fungi (AMF) to stressful soil
      conditions and the relative contribution of spores of these fungi to plant
      colonization were examined in a Portuguese salt marsh. Glomus geosporum is
      dominant in this salt marsh. Using tetrazolium as a vital stain, a high
      proportion of field-collected spores were found to be metabolically active at all
      sampling dates. Spore germination tests showed that salt marsh spores were not
      affected by increasing levels of salinity, in contrast to two non-marsh spore
      isolates, and had a significantly higher ability to germinate under increased
      levels of salinity (20 per thousand) than in the absence of or at low salinity
      (10 per thousand). Germination of salt marsh spores was not affected by soil
      water levels above field capacity, in contrast to one of the two non-marsh spore
      isolates. For the evaluation of infectivity, a bioassay was established with
      undisturbed soil cores (containing all types of AM fungal propagules) and soil
      cores containing only spores as AM fungal propagules. Different types of
      propagules were able to initiate and to expand the root colonization of a native
      plant species, but spores were slower than mycelium and/or root fragments in
      colonizing host roots. The AM fungal adaptation shown by this study may explain
      the maintenance of AMF in salt marshes.

PMID- 12811644
TI  - The success of data collection in the palliative setting--telephone or clinic
      follow-up?
AB  - Assessment of outcomes is essential in order to improve available palliative
      treatments. Collecting follow-up information can be a challenging task in the
      palliative setting. We compared the effectiveness of data collection by telephone
      contact and clinic visit in 112 patients with brain metastases treated with whole
      brain radiotherapy. The first 56 patients (group A) were followed by telephone
      only. The second 56 patients (group B) were asked to attend an outpatient clinic
      appointment 4 weeks after radiotherapy. Successful contact was defined as
      obtaining data at week 4. Patients in the two groups did not differ significantly
      with regard to age, sex, performance status, primary site, number of brain
      metastases, or the treatment given. The proportions of patients with successful
      follow-up contact at week 4 were 45% and 61% in groups A and B, respectively ( P
      = 0.09). The quality of the collected data did not differ significantly between
      the two groups. The side effects and responses to therapy were similar. However,
      there were significantly more patients with a reduced dose of dexamethasone among
      the successful contacts in group B, which probably reflected the better condition
      of the patients coming back to clinic at week 4. In conclusion, there was a trend
      towards more successful data collection in our clinic follow-up. Some of the
      observed outcome data suggest that the two methods of follow-up might be reaching
      different populations of patients; considering this and the high attrition rate,
      a combined follow-up strategy of clinic and telephone contacts might be the best
      strategy.

PMID- 12811645
TI  - Role of extracellular matrix in kidney development and repair.
AB  - Extracellular matrix (ECM) molecules and their receptors exert a dynamic role in
      cell-matrix interactions during kidney development and repair processes. They
      provide a physical substratum for the spatial organization of the cells, but also
      regulate cell growth and proliferation by interacting with growth factors. In
      addition, they can regulate signal transduction pathways by binding to integrins
      or by modulating the activity of signaling molecules such as Wnts. ECM and ECM
      related molecules control multiple (if not all) steps of kidney development,
      including ureteric bud branching morphogenesis, mesenchymal condensation, nephron
      formation, terminal differentiation of renal tubules, and glomerular basement
      membrane assembly. Their role still needs to be better documented in renal
      repair. The emergence of conditionally mutated mice for basement membrane
      components will provide a useful tool to demonstrate further the involvement of
      ECM and ECM-related proteins in development and repair.

PMID- 12811647
TI  - Acute renal failure complicating neonatal sub-galeal hemorrhage.

PMID- 12811646
TI  - Sodium and potassium clearances by the maturing kidney: clinical-molecular
      correlates.
AB  - A temporal dissociation exists between the early appearance of sodium absorptive
      and later detection of potassium secretory processes in the maturing rabbit
      collecting duct. To extend the latter findings to the human, we sought to
      correlate developmental changes in renal sodium and potassium clearances with the
      molecular expression of corresponding ion channels in kidneys of premature
      infants. In a longitudinal prospective study of 23- to 31-week gestational age
      (GA) infants, sodium, potassium, and creatinine clearances were measured weekly
      for 5 weeks and the absolute and fractional excretions of sodium (FE(Na)) and
      potassium (FE(K)) calculated. Gene-specific probes were used to assess steady
      state abundance of mRNA encoding the sodium channel ENaC and potassium channel
      ROMK in homogenates of human kidneys (obtained from the Anatomic Gift
      Foundation). Although urinary losses of sodium in infants <approximately 28 weeks
      GA exceeded intake, leading to a state of negative sodium balance, most infants
      >/=28 weeks and all infants >approximately 32 weeks GA achieved a state of
      positive balance, a maturational process associated with a decrease in FE(Na )and
      increase in ENaC. Infants >approximately 30 weeks GA maintained a state of
      positive potassium balance. We noted a twofold reduction in FE(K )after
      approximately 26 weeks GA and no change in ROMK abundance during the
      developmental window studied. We speculate that the developmental regulation of
      renal ENaC expression contributes, at least in part, to the decrease in FE(Na
      )observed with advancing GA, and that in the human, as in the rabbit, there is a
      delay between the maturation of sodium absorptive and potassium secretory
      pathways.

PMID- 12811648
TI  - Urinary tract infections, VUR, and autosomal dominant polycystic kidney disease.
AB  - This case series of 16 patients with autosomal dominant polycystic kidney disease
      (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI).
      Radiological evaluation revealed that each of these patients had vesicoureteral
      reflux (VUR). The frequency of VUR was significantly higher in the patients with
      ADPKD compared with otherwise healthy age-matched children who underwent testing
      after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an
      associated somatic anomaly in children with ADPKD that may contribute to the
      occurrence of UTI in this patient population.

PMID- 12811649
TI  - Kawasaki disease misdiagnosed as acute pyelonephritis.

PMID- 12811650
TI  - Chronic renal insufficiency in children: the 2001 Annual Report of the NAPRTCS.
AB  - End-stage renal disease (ESRD) is a major cause of morbidity in children. Besides
      its high cost to society, ESRD carries significant mortality. Chronic renal
      insufficiency (CRI) often precedes ESRD. Identifying factors that correlate with
      the rate of progression to ESRD is beneficial in the management of children with
      CRI. Since 1994 the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) has extended its registry to include children with CRI, defined as
      creatinine clearance ( C(Cr)) <75 ml/min per 1.73 m(2). As of January 2001, our
      database registered 4,666 children (<20 years of age) with CRI. Data analysis
      showed that at least 40% of patients entered had congenital urological anomalies;
      39% of patients were followed for at least 3 years. Follow-up data showed that
      31% of all registered patients progressed to ESRD by the end of the reporting
      period. There was a correlation between CRI and several co-morbid clinical
      factors: low hematocrit, hypoalbuminemia, hypocalcemia, hyperphosphatemia, and
      hyperparathyroidism, and the rate of progression to ESRD. Primary clinical
      diagnosis and the age at entry into registry were additional factors that
      correlated with the rate of progression to ESRD. The main cause of
      hospitalization in this registry was infection, which accounted for 45% of
      hospital admissions. Growth delay measured by standard deviation score at
      baseline was -1.40 at the time of registration. Our data suggest potential areas
      of improved care that could impact the onset of ESRD.

PMID- 12811651
TI  - Arterial hypertension with brachydactyly in a 15-year-old boy.
AB  - Autosomal dominant brachydactyly with hypertension is the only form of monogenic
      hypertension which is not sodium dependent. The disease is characterized by
      brachydactyly type E, short stature, arterial hypertension and aberrant loop of
      posterior inferior cerebellar artery (PICA) causing neurovascular conflict. So
      far the syndrome was described in one family in Turkey and two in Canada. We
      report a case of a 15-year-old boy who was admitted because of arterial
      hypertension 160/100 mmHg. He complained also of attacks of bilateral numbness of
      hands with deterioration of visual field. Examination revealed short stature (156
      cm) and bone deformities of hands and feet consistent with brachydactyly type E.
      Ophthalmoscopy showed mild narrowing of retinal arteries. Serum electrolytes,
      blood gases, and renal function were normal. Renin activity and aldosterone
      concentrations were raised, and 24-h urinary excretion of catecholamines and
      urinary steroid profile were in normal range. Renal Doppler ultrasound was
      normal, but renal scintigraphy suggested vascular changes in the left kidney.
      Echocardiographic examination, besides mild left ventricular hypertrophy, was
      normal. Magnetic resonance angiography (angio-MR) revealed bilateral abnormal
      PICA loops and neurovascular conflict. Spiral angiotomography of renal arteries
      revealed narrow additional left renal artery. Both nonconsanguineous parents and
      younger brother were healthy, with normal height, without bone deformities, and
      had normal intracranial vessels. Amlodipine and metoprolol were given, and blood
      pressure lowered to 143/87. Adding rilmenidine gave no effect and enalapril was
      then added. It led to further improvement in blood pressure control. To our
      knowledge, this is the first pediatric description of a sporadic form of
      autosomal dominant brachydactyly with hypertension with abnormalities of brain
      and renal arteries.

PMID- 12811653
TI  - Long-term linear growth of children with severe steroid-responsive nephrotic
      syndrome.
AB  - The present study was designed to evaluate the risk of permanent linear growth
      impairment in a selected group of 42 children with steroid-dependent nephrotic
      syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome
      (FRNS). Longitudinal height measurements were available in all patients from the
      onset of the disease for a mean follow-up of 11.7+/-3.5 years. During the
      prepubertal period, patients lost 0.49+/-0.6 height SD score (HtSDS) ( P<0.001).
      Twenty-three patients have reached their final height with an average loss of
      0.92+/-0.8 HtSDS from the onset of their disease ( P<0.001) and 0.68+/-0.7 from
      their target HtSDS ( P<0.001). The pubertal growth spurt was mildly delayed in
      male but not female patients. Steroid therapy, calculated as the mean duration of
      prednisone (PDN) treatment or as the average cumulative PDN dose, was the only
      predictor of poor growth evolution. Partial catch-up growth occurred after PDN
      withdrawal. Children with early onset NS and adolescent patients, who were still
      receiving PDN after the age of 9 years in girls and 11 years in boys, were at
      higher risk for HtSDS loss. In conclusion, children with severe steroid
      responsive NS are at risk of permanent growth retardation secondary to prolonged
      courses of steroid treatment.

PMID- 12811652
TI  - Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin
      blockade.
AB  - Steroid-resistant nephrotic syndrome of childhood poses a dilemma in attempting
      to balance toxicity of medications against long-term prognosis. This report
      presents our preliminary experience with the novel use of combined mycophenolate
      mofetil (MMF) and angiotensin blockade (AB) in the treatment of nine children and
      young adults with focal glomerulosclerosis (FSGS). All patients were steroid
      resistant and had failed conventional treatment regimens. Prior to the initiation
      of the MMF-AB protocol, the patients were pre-treated with weekly intravenous
      methylprednisolone (MP) (15 mg/kg per week) for 4-8 weeks. Angiotensin-converting
      enzyme inhibitors and/or angiotensin receptor blockers were begun when
      intravascular volume was restored. MMF was given at a dose of 250-500 mg/m(2) per
      day. Proteinuria, as measured by urine protein/creatinine ratios (Up/c),
      decreased by 43% following MP ( P<0.05). After 6 months of MMF-AB protocol, the
      Up/c was 72% below baseline ( P<0.01). This level was maintained for a minimum of
      24 months of observation. Similarly, hyperlipidemia, as measured by total
      cholesterol and triglycerides, improved significantly with treatment (536+/-163
      to 265+/-70 mg/dl, 447+/-168 to 230+/-92 mg/dl, respectively, P<0.01). Our data
      support the use of MMF and AB for treatment of steroid-resistant FSGS when other
      conventional treatments have failed and/or induced toxicity.

PMID- 12811655
TI  - Defective proximal tubular function in a patient with I-cell disease.
AB  - A girl with a proven diagnosis of I-cell disease is presented. Proximal tubular
      dysfunction was characterized by increased excretion of low molecular proteins,
      aminoaciduria, hyperphosphaturia, and high/slightly increased urinary calcium.
      The concentration of 1,25-dihydroxycalciferol in serum was increased. Rickets
      were present on X-rays. As the proximal tubular dysfunction resembles the
      dysfunction in Dent disease, one can speculate about a common pathogenesis.
      Impairment of acidification in lysosomes due to loss of function of the chloride
      5 channel impairs intralysosomal protease activity in Dent disease, while in I
      cell disease the intralysomal protease activity is lacking.

PMID- 12811656
TI  - Laparoscopic resection of type I choledochal cyst.
AB  - Type I choledochal cyst is a rare saccular or fusiform congenital dilatation of
      the extrahepatic biliary tract. It is usually treated by laparotomy at which the
      cyst is completely excised and a Roux-en-Y hepaticojejunostomy is performed to
      establish biliary enteric drainage. We report the laparoscopic excision and
      hepaticoduodenostomy of type I choledochal cyst in two girls aged 1 and 3 years.
      The entire procedure was performed laparoscopically using needlescopic
      instruments. A 7-mm telescope port was inserted at the umbilicus, a 3-mm port in
      the right upper quadrant, and a 6-mm port in left upper quadrant. An additional 3
      mm fan-shaped liver retractor was passed through the abdominal wall without a
      trocar. The gallbladder and choledochal cyst was dissected and removed en bloc.
      The lower end of the common bile duct was closed with 5-0 polydioxanone. The
      duodenum was anastomosed to the common hepatic duct below the confluence of the
      right and left hepatic ducts. There were no intraoperative complications, and the
      children were asymptomatic with no episodes of cholangitis at 6 months follow-up.
      Pediatric surgeons trained in advanced laparoscopic techniques including
      intracorporeal suturing can perform laparoscopic repair of choledochal cyst
      safely.

PMID- 12811657
TI  - Rupture of the lesser gastric curvature after a Heimlich maneuver.
AB  - BACKGROUND: We present a case of lesser gastric curvature injury after a Heimlich
      maneuver due to obstruction of the breathing tract that was repaired by
      laparoscopic surgery. METHODS: A patient with perforation of the lesser gastric
      curvature as a result of closed abdominal traumatism was operated on using the
      laparoscopic approach with the use of four trocars as work openings. With this
      technique, the diagnosis was confirmed, the injury repaired, and the abdominal
      cavity washed. RESULTS: The postoperative period was favorable and the patient
      was released from the hospital on day 7 without any complications. CONCLUSIONS:
      Laparoscopic surgery can be technically reproduced in the treatment of gastric
      injury as a result of closed abdominal traumatism.

PMID- 12811658
TI  - Hemobilia.
AB  - BACKGROUND: Laparoscopic procedures are safe and effective treatment methods in
      experienced hands. However, complications have been reported for laparoscopic
      procedures. One of the complications of laparoscopic cholecystectomy is vascular
      injuries. Hepatic and cystic artery injuries may occur alone or in association
      with bile duct injury. Bleeding from arterial injury may be seen during operation
      or in the late postoperative period. One of the most significant pathologies
      leading to this rare phenomenon is hemobilia. METHODS: We present a case of a 62
      year-old woman who underwent routine laparoscopic cholecystectomy for
      cholelithiasis at another hospital. She presented 6 months later with the
      clinical feature of upper gastrointestinal bleeding. RESULTS: There was a 42 x 40
      x 11 mm anechoic lesion and an echoic pattern compatible with a metallic object
      was found in the subhepatic region using abdominal ultrasonography. In the
      endoscopic examination, fresh blood was found in the stomach. The source of
      hemorrhage could not be identified. Bulbus duodeni was normal but a fresh clot on
      the papilla of Vateri was seen on gastroduodenoscopic examination. Laparotomy was
      performed and the provisional diagnosis of hemobilia was reached. The injured
      hepatic artery and pseudoaneurysmatic structure were repaired. CONCLUSION:
      Hemobilia is a late complication of laparoscopic cholecystectomy. We believe that
      it is important to take into consideration that bile duct injuries may be
      accompanied by arterial pathology.

PMID- 12811659
TI  - First report on sequential totally endoscopic thymomectomy and adrenalectomy
      using computer-enhanced telemanipulation.
AB  - BACKGROUND: Laparoscopic adrenalectomy is considered the standard method for
      removal of benign adrenal tumors, regardless of hormone activity. Minimally
      invasive surgery for thymomectomy aims at limited approaches, avoiding complete
      sternotomy or large thoracotomy. METHODS: We report on a case in which totally
      endoscopic thymomectomy and adrenal gland resection were performed sequentially
      using a computer-enhanced telemanipulation system within 3 weeks. RESULTS:
      Operating time was 4.5 h for totally endoscopic adrenalectomy and 1.5 h for
      totally endoscopic thymomectomy. The patient was transferred to the normal ward
      on the day of operation after either procedure and had an uneventful recovery.
      Pathology yielded no malignancy in both cases. CONCLUSION: This report
      demonstrates the safety and feasibility of various totally endoscopic procedures
      performed sequentially.

PMID- 12811660
TI  - Comparison of three-field esophagectomy for esophageal cancer incorporating open
      or thoracoscopic thoracotomy.
AB  - BACKGROUND: Thoracoscopic esophagectomy for esophageal cancer has been performed
      as an alternative to open surgery to reduce surgical trauma. However, its effect
      on pulmonary function, exercise tolerability, and quality of life is unknown.
      METHODS: Fifty-one patients with esophageal cancer underwent thoracic
      esophagectomy with radical lymphadenectomy by posterolateral thoracotomy (29
      cases) or thoracoscopic surgery (22 cases). Patients performed spirometry and
      exercise tolerance testing and completed a quality-of-life questionnaire before
      and 3 months after surgery. RESULTS: Pre-to-postoperative change in vital
      capacity was 74.3 +/- 10.6% in the thoracotomy group and 84.9 +/- 10.4% in the
      thoracoscopy group (p = 0.021). Maximum oxygen uptake was similar, but dyspnea
      was the more common factor limiting exercise tolerance postoperatively in the
      thoracotomy group. Change in pre-to-postoperative performance status was 1.20 +/-
      0.62 in the thoracotomy group and 0.55 +/- 0.51 in the thoracoscopy group (p =
      0.0003). CONCLUSIONS: Thoracoscopic esophagectomy for esophageal cancer has
      better preservation of pulmonary function and quality-of-life.

PMID- 12811661
TI  - Reaction times and the decision-making process in endoscopic surgery.
AB  - BACKGROUND: There are times during endoscopic procedures when the displayed
      surgical field does not align with the actual field due to rotation of the
      camera. The surgeon's performance may deteriorate under this situation. However,
      the effects of misalignment on the decision-making processes during endoscopic
      procedures have not been fully explored. The present study addresses this problem
      and suggests a technique that may be used to alleviate it. METHODS: Two
      experiments were completed in a mock endoscopic surgical setup where the image of
      the work plane inside the training box was either projected on a vertical monitor
      placed at eye level or superimposed over the training box by means of a half
      silvered mirror. The work plane consisted of a start plate and four target
      plates. The experimenter varied the number of choices of target location among
      one, two, and four target choices. Rotating the camera about its longitudinal
      axis misaligned the displayed and the actual work plane. There were two
      experiments that differed in task difficulty. The task in experiment 1 was to
      touch the target plate, whereas the task in experiment 2 was to reach, grasp, and
      transport the object from the target to the start plate. RESULTS: Experiment 1
      showed that reaction time increased with the number of the choices for a touch
      task, in accordance with the Hick-Hyman law. Using a grasp-and-transport task,
      experiment 2 replicated experiment 1 and extended the results to show that the
      use of a superimposed image display facilitated the decision-making process,
      leading to shorter reaction times compared to the vertical image display.
      DISCUSSION: During endoscopic procedures, the surgeon needs to translate indirect
      perceptions to instrument-mediated actions by "mapping" them through sensorimotor
      integration. The superimposed image alleviates the mental load of spatial
      transformations by reducing the difficulty of the required sensorimotor mapping.
      These findings have important implications for the design of high-quality
      superimposed display technologies.

PMID- 12811662
TI  - Needlescopic appendectomy.
AB  - BACKGROUND: In this paper, we compare our experience with the techniques of
      needlescopic appendectomy (NA) (2-mm instruments) for the treatment of acute
      appendicitis with the more conventional approach of a laparoscopic appendectomy
      (LA). METHODS: We did a retrospective review of patients who underwent NA for the
      diagnosis of acute appendicitis between August 1996 and January 2002. Variables
      including operative time, blood loss, postoperative time to discharge, intra- and
      postoperative complications were analyzed and compared to data from control
      patients who had undergone an LA for acute appendicitis. RESULTS: The NA group
      had a longer average operating time (54.5 +/- l3 vs. 42.5 +/- 12.6 min, p =
      0.0001) and a longer postoperative hospital stay (2.1 +/- 1.4 vs. 1.3 +/- 1.1
      days, p = 0.01). Blood loss was similar for the two groups. CONCLUSIONS: With the
      exception of superior cosmesis, NA appears to have little advantage over the
      better-established LA; moreover, it has some disadvantages. A clearer benefit of
      this procedure over LA, as well as improvements in instrumentation, needs to be
      shown before it can be widely accepted.

PMID- 12811663
TI  - Iatrogenic bile duct injuries.
AB  - BACKGROUND: The real incidence of bile duct injury (BDI) during laparoscopic
      cholecystectomy (LC) is not known. METHODS: Using questionnaires, we analyzed
      91,232 LC performed by 170 surgical units in Brazil between 1990 and 1997.
      RESULTS: A total of 167 BDI occurred (0.18%); the most frequent were Bismuth type
      1 injuries (67.7%). Most injuries (56.8%) occurred at the hands of surgeons who
      had surpassed the learning curve (50 operations). However, the incidence dropped
      with increasing experience; it was 0.77% at surgical departments with <50
      operations vs 0.16% at departments with >500 operations. The diagnosis was made
      intraoperatively in 67.7%, but it was based on intraoperative cholangiography in
      only 19.5%. The procedure was converted to open surgery in 85.8% when the
      diagnosis of injury occurred intraoperatively, and laparotomy was performed in
      90.7% when the injury was diagnosed postoperatively. The mean hospitalization
      time was 7.6 +/- 5.9 days, the major complications were stenosis and fistulas,
      and the mortality rate was 4.2%. CONCLUSION: The incidence of BDI after LC is
      similar to that reported for the open procedure. BDI increases mortality and
      morbidity and prolongs hospitalization; therefore, all efforts should be made to
      reduce its incidence.

PMID- 12811664
TI  - Acute bile duct injury. The need for a high repair.
AB  - BACKGROUND: An immediate repair is considered optimal in acute biliary duct
      injuries; however, it may prove to be a challenge, because such repairs are
      usually performed on small ducts whose viability cannot always be determined.
      METHODS: We performed a retrospective review of the charts of patients with acute
      bile duct injury who underwent repair at a tertiary care academic university
      hospital. A total of 204 patients with acute bile duct injury were seen between
      1989 and 2002. Of these, 30 were repaired within minutes to hours after the
      injury. These patients were divided into two groups. Group I patients had a Roux
      en-Y hepatojejunostomy below the hepatic junction; Group II patients had a Roux
      en-Y hepatojejunostomy at the junction level. We then performed a long-term
      evaluation of anastomosis function in these patients, using clinical,
      radiological, and laboratory. RESULTS: Twenty-eight injuries were secondary to a
      laparoscopy; the other two resulted from open cholecystectomies. All of the
      patients suffered complex injuries with complete section of the duct and
      substance loss (Strasberg E). There were 12 patients in group I and 18 in group
      II. Three cases in group I (25%) and one in group II (5%) developed anastomosis
      dysfunction. Mean follow-up was 56 months (range, 12-80) in group I and 52 months
      (range, 10-76) in group II. Two cases in group I (16%) and none in group II (0)
      required reoperation (p < 0.05). CONCLUSIONS: In the acute setting, complex
      lesions should be treated with a high bilioenteric anastomosis (at the junction
      level) in the first attempt at repair. Lower-level anastomoses are associated
      with a higher dysfunction rate and the need for radiological manipulation and
      reoperation. Also, stenosis of the anastomosis secondary to undetected duct
      ischemia in the acute repair is more frequent in low bilioenteric anastomoses.

PMID- 12811665
TI  - Gastrointestinal symptoms are more intense in morbidly obese patients.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass is an effective treatment for
      morbid obesity. However, little information is available on gastrointestinal (GI)
      symptomatology in this population. This study compares GI symptoms in morbidly
      obese patients to that of control subjects. METHODS: A previously validated, 19
      point GI symptom questionnaire was administered prospectively to each patient
      seen for surgical consultation for morbid obesity. The symptoms were then grouped
      into 6 clusters as follows: (1) abdominal pain, (2) irritable bowel, (3) GERD,
      (4) reflux, (5) sleep disturbance, (6) dysphagia. The result of each cluster of
      symptoms expressed as mean +/- standard deviation of obese versus control is
      compared using student's t-test with significance p = 0.05. RESULTS: Forty-three
      patients (40 female, 3 male) age 37.3 +/- 8.6 with BMI 47.8 +/- 4.9, and 36
      healthy control subjects (23 female, 13 male), age 39.8 +/- 11.2, completed the
      questionnaire. Results of each cluster for morbid obese vs control subjects are
      expressed as mean +/- standard deviation: Abdominal pain 25.3 +/- 18.0 vs 12.1 +/
      11.4, p = 0.0002; irritable bowel 23.0 +/- 14.8 vs 15.6 +/- 13.3, p = 0.02; GERD
      40.3 +/- 18.9 vs 22.3 +/- 16.1, p = 0.0001; reflux 29.9 +/- 19.0 vs 11.8 +/-
      13.4, p = 0.0001; sleep disturbance 50.6 +/- 28.9 vs 32.9 +/- 26.8, p = 0.006;
      dysphagia 10.9 +/- 15.6 vs 7.2 +/- 10.6, p = NS. CONCLUSIONS: Morbidly obese
      patients experience more intense GI symptoms than normal subjects, whereas
      dysphagia is equivalent to normal subjects. These data may be important in
      counseling patients and understanding that their complaints are legitimate.
      Follow-up in the postoperative period is needed to determine if these symptoms
      are improved with an operation.

PMID- 12811666
TI  - Laparoscopic omental fixation technique versus open surgical placement of
      peritoneal dialysis catheters.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is an effective form
      of treatment for patients with end-stage renal disease. Open insertion of
      peritoneal dialysis (PD) catheters is the standard surgical technique, but it is
      associated with a relatively high incidence of catheter outflow obstruction and
      dialysis leak. Omental wrapping is the most common cause of mechanical problems.
      The purpose of this study was to determine the efficacy of the laparoscopic
      omental fixation technique to prevent the obstruction caused by omental wrapping
      and also to compare this laparoscopic technique with open peritoneal dialysis
      catheter insertion with respect to postoperative discomfort, complication rates,
      and catheter survival. METHODS: Between March 1998 and October 2001, 42 double
      cuff, curled-end CAPD catheters were placed in 42 patients. The outcomes of the
      21 patients in whom the PD catheters were placed laparoscopically with omental
      fixation technique were compared with those of the 21 patients in whom the
      catheters were placed with open surgical technique. Recorded data included
      patient demographics, catheter implantation method, early and late complications,
      catheter survival, and catheter outcome. RESULTS: Early peritonitis episodes
      occurred in 8 of 21 patients (38.0%) in the open surgical group (OSG) versus 2 of
      21 patients (9.5%) in the laparoscopic omental fixation group (LOFG) ( p < 0.05);
      late peritonitis episodes occurred in 3 of 21 patients (14.2%) in the OSG versus
      1 of 21 patients (4.7%) in the LOFG ( p < 0.05). Early exit site infection
      occurred in 8 of 21 patients (38.0%) in the OSG versus 4 of 21 patients (19.0%)
      in the LOFG ( p < 0.05), with many catheter-related problems in the conventional
      surgical group. There was no outflow obstruction in the LOFG. The conventional
      procedure was faster than the laparoscopic omental fixation technique. Analgesic
      requirements and hospital stay were less in the laparoscopic group. Laparoscopic
      surgery also enabled diagnosis of intraabdominal pathologies and treatment of the
      accompanying surgical problems during the same operation. Occult inguinal hernia
      was diagnosed in 2 patients, inguinal hernioplasty was performed in 4 patients,
      adhesiolysis was performed in 8 patients who had previous abdominal surgery, and
      liver biopsy was taken in 2 patients. Ovarian cystectomy was performed in another
      patient during laparoscopic CAPD catheter placement. CONCLUSION: The laparoscopic
      omental fixation technique (described by Ogunc and published in 1999) is a highly
      effective and successful method for preventing obstruction due to omental
      wrapping with a better catheter survival. Laparoscopic surgery also allows the
      diagnosis and treatment of the accompanying surgical pathologies during the same
      operation.

PMID- 12811667
TI  - Mechanical small bowel obstruction precipitated by colonoscopy.
AB  - Mechanical small bowel obstruction (SBO) is rare complication of colonoscopy. We
      present a patient who developed SBO 24 h after surveillance colonoscopy. Four
      years prior to this procedure, he had undergone augmentation cecocystoplasty with
      continent ileal conduit. He subsequently underwent laparotomy and lysis of a band
      adhesion that caused extrinsic compression of the ileum proximal to
      ileotransverse colostomy. We further review the literature, describe the salient
      features of colononoscopy-induced bowel obstruction, and identify the risk
      factors for this unusual complication.

PMID- 12811668
TI  - Laparoscopically assisted enterolithotomy for a gallstone ileus in an atypical
      location.
AB  - Mechanical intestinal obstructions caused by gallstones occur in approximately 1%
      to 2% of cases. In most of the patients, the obstruction occurs at the ileocecal
      valve. However, gallstones may cause obstruction anywhere along the
      gastrointestinal tract from the stomach to the sigmoid colon. Laparoscopically
      assisted enterolithotomy can be used as a treatment method. This report describes
      a case in which a gallstone blockage caused a mechanical obstruction in an
      atypical location, which was successfully treated with a laparoscopically
      assisted approach.

PMID- 12811669
TI  - Laparoscopic tension-free hernioplasty for lumbar hernia.
AB  - Lumbar hernia, a defect of the posterior abdominal wall, is a very rare
      condition. The repair of a posterior abdominal wall hernia by simply closing the
      hernia port with sutures may not be adequate, especially when the herniation is
      due to a weakness in the abdominal wall. Recently, a simple, logical method of
      tension-free repair has become a popular means for the treatment of various
      abdominal wall hernias. Previous studies have advocated the use of tension-free
      repair for lumbar hernia; the technique uses a mesh replacement and requires an
      extensive incision. Herein we present a case of superior lumbar hernia. Our
      technique consisted of a laparoscopic tension-free hernioplasty with the
      application of a Prolene mesh. This technique, which provides an excellent
      operative view, is safe, feasible, and minimally invasive. We conclude that
      laparoscopic tension-free repair should be the preferred option for the treatment
      of lumbar hernia.

PMID- 12811670
TI  - Prolonged abdominal wall pain caused by transfascial sutures used in the
      laparoscopic repair of incisional hernia.
AB  - The use of transfascial sutures in the laparoscopic repair of incisional hernia
      has considerably facilitated the accurate intraperitoneal placement and fixation
      of the synthetic mesh. The laparoscopic procedure has a number of advantages,
      including less morbidity and pain. Moreover, the use of a mesh prosthesis results
      in a low rate of hernia recurrence. Despite the benefits associated with this
      technique, several (minor) complications have been documented. Herein we describe
      a case of prolonged abdominal wall pain after laparoscopic hernia mesh repair
      that was caused by the use of transfascial sutures.

PMID- 12811671
TI  - Abortion trends 1990-1999 in a Swiss region and determinants of abortion
      recurrence.
AB  - OBJECTIVE: To assess age- and nationality-specific trends in abortion rates over
      the last decade, and to describe women's characteristics, identifying risk
      factors for repeated abortion. METHODS: From 1990-1999, the Health Department of
      Canton Vaud (Switzerland) received 13'857 abortion requests from residents aged
      14-49. Population data were obtained to compute rates. RESULTS: Both the number
      of abortions (1400 annually) as well as their rate (8.9 per thousand women [95%
      confidence interval (CI) 7.3-10.5]) were stable over the decade in question. The
      rate of abortion for foreign women, especially from ex-Yugoslavia and Africa, was
      twice that for Swiss women. Half of the requests came from single women, 43% had
      a low education level, and half were childless. The main reason for requesting
      termination of pregnancy was psychosocial (93%). The mean gestational age was 7.7
      weeks (SD +/- 2.3), but 96% of requests were submitted before 12 weeks. Sixty
      three percent of women reported that they had used no contraception, 36% the
      condom and 17% the pill. Among requests, the adjusted risk of repeated abortion
      (22% of abortion candidates) was greater among divorced/separated/widowed women
      (odds ratio [OR] 1.9 [95% CI 1.5-2.4]), unemployed women (OR 1.8 [95% CI 1.5
      2.1]), and those who had not attended university (OR 1.6 [95% CI 1.1-2.2]).
      CONCLUSIONS: Although Swiss law only permitted abortion under strict conditions,
      this procedure was widely available in Vaud, which nevertheless has one of the
      lowest rates worldwide. Efforts must be intensified to ensure universal access to
      family planning services, especially for foreign women and adolescents.
      Professionals should also target "repeaters" to provide personalised counselling.

PMID- 12811672
TI  - Tetanus immunisation in geriatric patients with accidental wounds: how much is
      needed?
AB  - OBJECTIVE: In the industrialised world, the elderly carry the highest risk for
      tetanus. This prospective serological study was performed to evaluate the
      reliability of tetanus immunisation histories and the antibody response to
      tetanus vaccinations in the elderly. METHODS: 40 individuals >65 years with a
      bleeding trauma were included in the study. Their tetanus vaccination histories
      were investigated, and accordingly a single booster (group A, n = 7), or a three
      dose basic immunisation against tetanus (group B, n = 33) was provided. In
      addition, tetanus antitoxin levels were determined. RESULTS: Age varied between
      67 and 95 years. Inconsistencies regarding the vaccination history were found
      between patients and their physicians in 30% (12/40), between patient statements
      and vaccination documents in 57.1% (8/14) and between physicians' records and
      vaccination documents in 35.7% (5/14). Antitoxin titres >0.15 IU/ ml were
      considered protective, giving a seroprevalence of 92.5%. Sensitivities and
      negative predictive values for tetanus immunity were 30.6% and 10.7% based on
      patient histories and 2.8% and 7.9% based on physicians' records. In group A,
      after the single booster immunisation the median titre rose from 1.2 to 14.2
      IU/ml, in group B from 0.9 to 5.3 IU/ml after the first, and to 9.6 IU/ml after
      the third tetanus toxoid dose (p <0.001 using Friedman's test). CONCLUSIONS: In
      Switzerland, elderly patients with a tetanus prone wound provide an unreliable
      vaccination history but their seroprotection against tetanus is high. A single
      booster for secondary immunisation is therefore sufficient. It is not necessary
      to take the largely unreliable vaccination history into account.

PMID- 12811673
TI  - Use of alternative medicine by patients with cancer in a rural area of
      Switzerland.
AB  - BACKGROUND: Many cancer patients use alternative therapies in addition to
      conventional treatment. In a survey among such patients, we assessed the
      prevalence of and the motivation for alternative therapy use in a rural area of
      Switzerland. METHODS: From 1st February to 30th November 2001, we interviewed 108
      patients treated in the oncology outpatient clinic of the Langenthal District
      General Hospital, Switzerland, using a structured questionnaire. 77% of the
      patients were female. 49% of the patients (i.e., 64% of the female patients)
      suffered from breast cancer. RESULTS: 42 (39%) of all patients had used an
      alternative therapy in addition to conventional treatment at least once.
      Mistletoe preparations were by far the most popular with a prevalence of 74%.
      Homeopathy (24%) and cancer diets (12%) were used less often. 79% of the patients
      seeking help from alternative treatment informed their treating oncologist and/or
      medical practitioner accordingly. 57% of the doctors encouraged their patients to
      continue the alternative treatment, none discouraged the patient to do so. The
      main reasons for the use of alternative therapy were: the desire to feel more
      hopeful (83%); "to do as much as possible myself to cure the disease" (83%); and
      to harness mental energy (62%). Only 19% of the patients hoped to be cured of
      cancer by alternative therapy. CONCLUSIONS: The motivation to seek help from
      alternative treatment is not based on a distrust of conventional care.
      Maintaining hope and taking an active role in self-care are the main stimuli for
      using alternative medicine.

PMID- 12811674
TI  - Evaluation of dexamethasone suppression test in fibromyalgia patients with or
      without depression.
AB  - OBJECTIVE: While in most healthy persons dexamethasone administration suppresses
      cortisol synthesis from the adrenal cortex, such suppression is not usually
      observed in patients with depression. We set out to investigate whether the
      dexamethasone suppression test (DST) reveals any neurobiological relationship
      between fibromyalgia (FM) and depression related to the hypothalamic-pituitary
      adrenal (HPA) axis. METHOD: To discover a relationship between depression and FM
      we performed the DST in 20 FM patients with depression, 26 FM patients without
      depression and 20 healthy subjects serving as a control group. RESULTS: Compared
      with the control group the cortisol level was found to be significantly higher in
      response to the DST in FM patients with depression (p = 0.03; z: -2.165), but not
      in those without depression (p = 0.153; z: -1.429). The cortisol level was not
      found to be statistically significant when patients with FM without depression
      were compared with the control group (p = 0.249; z: -1.152). In 7 FM patients
      with depression the DST failed to suppress cortisol; this was statistically
      significant compared with FM patients without depression (p = 0.014) and the
      control group(p = 0.008). Among FM patients without depression cortisol was not
      suppressed in one case. Cortisol was suppressed in all the controls. There was no
      statistically significant difference in cortisol suppression between FM patients
      without depression and the control group (p = 1.00). CONCLUSION: Our findings
      show that the DST reveals no neurobiological relationship between FM and
      depression related to the HPA axis.

PMID- 12811675
TI  - Neuromotor development from kindergarten age to adolescence: developmental course
      and variability.
AB  - The normal course of neuromotor development is described from 5 to 18 years of
      age. The data have been collected by use of the Zurich Neuromotor Assessment, a
      standardized testing procedure in which distinct motor tasks are judged with
      regard to timed performance and movement quality (associated movements of the
      contralateral and ipsilateral extremity, face, head and body). In the Zurich
      Growth and Development Studies, norms for these motor tasks have been established
      in 662 children and adolescents from middle class families. Neuromotor
      development is not a phenotypic entity, but evolves from motor functions of
      different complexity. With regard to timed performance and movement quality
      developmental course, gender differences and laterality vary considerably over
      age and among motor tasks. Thus, for a reliable assessment of the neuronotor
      developmental status in children, a standardized test instrument, well-trained
      examiners and normative data are required.

PMID- 12811676
TI  - Transient hyperopic refractive changes in newly diagnosed juvenile diabetes.
AB  - PURPOSE: To investigate transient hyperopic refractive changes in newly diagnosed
      juvenile diabetics and to evaluate their clinical course after starting intensive
      glycemic control of severe hyperglycaemia. METHODS: 20 hyperopic adolescents with
      newly diagnosed and uncomplicated type 1 diabetes, selected for this prospective
      study, were enrolled for a baseline examination and, after starting intensive
      insulin treatment, followed every two weeks during a four-month follow up.
      Standardised automated refraction and A-mode ultrasonography were performed. Poor
      metabolic control was an inclusion criteria. RESULTS: Refractive changes and
      hyperopic peaks preceded the start of the intensive insulin therapy in all
      diabetics and, thereafter, refraction decreased gradually with a maximum recovery
      time of 94 days. A statistically significant positive correlation between
      refractive changes and magnitude of plasma glucose concentrations as well as
      HbA1c percentages was observed (P <0.001). No significant modifications in the
      explored refractive components were recorded. CONCLUSIONS: Transient hyperopic
      changes are highly dependent on the magnitude of plasma glucose concentrations
      and rapid correction of hyperglycemia is strictly correlated with complete
      recovery of refraction. To account for this phenomenon, the sorbitol production
      via the polyol pathway with overhydration of the lens remains the best
      pathophysiological hypothesis at this time.

PMID- 12811677
TI  - Intraoperative parathormone measurement in patients with primary
      hyperparathyroidism: a prospective clinical study.
AB  - BACKGROUND: The objective of this pilot study was to evaluate the use of
      intraoperative iPTH measurement in combination with bilateral neck exploration in
      patients with primary hyperparathyroidism. METHODS: A prospective study was
      conducted in a single centre university hospital in Switzerland comprising 33
      patients with primary hyperparathyroidism undergoing neck surgery. No routine
      preoperative localisation studies were conducted. Intraoperative iPTH measurement
      was performed at defined times. Exploration was discontinued when iPTH fell below
      15% of baseline. RESULTS: For all patients with adenoma the median serum iPTH
      decreased to 11.9% (standard deviation 5.5%) of baseline concentrations. All
      patients with hyperplasia achieved normocalcaemia. At median follow-up of 17.7
      weeks neither recurrent nor persistent hypercalcaemia was observed. Eleven
      patients were explored unilaterally. CONCLUSION: Measurement of intraoperative
      serum iPTH is a helpful tool in the differentiation of single adenoma from
      hyperplastic glands. When we call for a strict 78% decrease in serum iPTH from
      base levels after 10 minutes, measurement of this marker protein even allows
      differentiation of single- from multi-glandular disease.

PMID- 12811678
TI  - Low serum total thyroxine and free triiodothyronine in patients with hepatic
      encephalopathy due to non-alcoholic cirrhosis.
AB  - PRINCIPLES: We evaluated serum thyroid hormone levels in non-alcoholic cirrhotic
      patients with and without hepatic encephalopathy. METHODS: 15 consecutive
      patients with hepatic encephalopathy secondary to non-alcoholic cirrhosis (8
      males and 7 females, age 37-75 years) and 33 non-alcoholic cirrhotic patients
      without encephalopathy (22 males and 11 females, age 36-74 years) were
      investigated. A control group consisted of 20 healthy subjects (10 men and 10
      women aged 26-69 years). The levels of serum triiodothyronine (T3), thyroxine
      (T4), thyrotropin (TSH), free T3 (FT3) and free T4 (FT4) were studied in serum
      samples drawn in the morning. Thyroid function tests were set in relation to the
      severity of hepatic dysfunction and to the presence or absence of hepatic
      encephalopathy. RESULTS: Serum levels of FT3 and total T4 (but not total T3 and
      FT4) were significantly lower in patients with hepatic encephalopathy compared to
      decompensated cirrhotic patients without encephalopathy (p = 0.006 for T4, P
      <0.05 for FT3). Prothrombin-time also differed significantly between
      decompensated cirrhotic patients (Child C) with and without encephalopathy groups
      (p = 0.002). CONCLUSIONS: These results suggest that patients with hepatic
      encephalopathy secondary to decompensated non-alcoholic cirrhosis are typified by
      low FT3 and low total T4, as well as by a prolonged prothrombin time. Low FT3
      does not obviously put patients at risk for hepatic encephalopathy, and thyroid
      parameters are secondary and late events.

PMID- 12811679
TI  - Drug strategies for the treatment of obesity.
AB  - There are three major classes of drugs for the treatment of obesity: (i)
      inhibitors of food intake, which reduce hunger perception and, consequently, food
      intake; the most representative are centrally acting neurotransmitters and
      intestinal or neural satiety peptides; (ii) inhibitors of nutrient absorption,
      which reduce energy disposal through a peripheral gastrointestinal mechanism; and
      (iii) thermogenic drugs, which increase energy expenditure. At present, there are
      only two drugs for long-term use: sibutramine, an inhibitor of both serotonin and
      norepinephrine reuptake, and orlistat, a lipase inhibitor that targets pancreatic
      lipases and reduces absorption of dietary fat. New treatments and better drugs
      are expected in the near future because of the rapid expansion of research in
      body-weight regulation mechanisms.

PMID- 12811680
TI  - Health aspects of probiotics.
AB  - Intestinal microbiota contribute in many different ways to our health;
      disturbances in the activity and/or composition of these microbiota may
      negatively influence health. In order to maintain a healthy intestinal
      microbiota, prebiotics and probiotics can be used. Selected probiotic strains
      safely shorten the duration of rotavirus diarrhea, relieve symptoms of lactose
      maldigestion and elicit beneficial immune-modulating effects. Other beneficial
      health effects have also been attributed to probiotics; however, these have not
      been sufficiently substantiated. Additional research into the mechanisms of
      probiotics is required.

PMID- 12811681
TI  - Bradykinin receptor antagonists: therapeutic implications.
AB  - Bradykinin (BK) is an important mediator of hyperalgesia, inflammatory diseases,
      asthma and cancer. It is a pro-inflammatory polypeptide that can cause pain,
      inflammation, increased vascular permeability, vasodilation, contraction of
      various smooth muscles and cell proliferation by stimulating B(1)and
      B(2)receptors. B(1) receptors are formed in vitro during trauma, inflammatory
      reactions and injury. B(2) receptors are most commonly distributed in the
      vascular and non-vascular smooth muscle, and in the heart. Numerous BK
      antagonists have been developed in recent years with the prime aim of treating
      diseases resulting from excessive BK formation. Non-peptide B(2) receptor
      antagonists are now being synthesized and are under intense experimental
      investigation at various research centers. The most clinically useful peptide and
      non-peptide BK antagonists must be stable against all BK-inactivating enzymes,
      orally active, and have a long half-life with minimal side effects. These BK
      receptor antagonists may have future novel therapeutic applications in various
      pathological conditions associated with the abnormal kinin system.

PMID- 12811682
TI  - Cinacalcet hydrochloride (Amgen).
AB  - Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc,
      are developing cinacalcet hydrochloride, the lead compound in a series of
      calcimimetics, for the potential treatment of primary and secondary
      hyperparathyroidism. Tecalcet hydrochloride was the first compound from this
      class to be extensively studied and most of the pharmacological data disclosed is
      for this compound. Cinacalcet hydrochloride was developed in an effort to improve
      on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.

PMID- 12811683
TI  - NO-naproxen (AstraZeneca).
AB  - NO-naproxen, consisting of the NSAID naproxen linked to a nitric oxide (NO)
      moiety, is under development by AstraZeneca plc, under license from NicOx SA, for
      the potential treatment of acute/chronic pain.

PMID- 12811685
TI  - [Cost-effectiveness in diagnosis of coronary artery disease].

PMID- 12811686
TI  - [Superparamagnetic iron oxide particles: current state and future development].
AB  - A wide range of applications for superparamagnetic iron oxide (SPIO) particles as
      contrast media for MRI has emerged over the last 15 years. SPIO particles can be
      manufactured with different particle sizes and surface coatings. Large SPIO
      particles (50-150 nm) predominantly produce a signal decrease or T2 -shortening
      and are used as contrast media for MRI of the liver and spleen. They have a high
      accuracy, especially in detecting liver metastases (approved for clinical use:
      AMI-25 (Endorem or Ferridex), SHU-555A (Resovist)). Smaller particles (about 20
      nm in diameter) show a different organ distribution and have a potential for
      improving noninvasive lymph node assessment or characterizing vulnerable
      atherosclerotic plaques (in clinical trials: AMI-227 [Sinerem or Combidex]).
      Particles with an optimized T1-relaxivity and prolonged intravascular circulation
      time can be used as blood pool contrast media for MR angiography. The currently
      investigated indications are MR angiography of the trunk, peripheral vessels, and
      coronary arteries (e.g., SHU-555 C (Supravist), VSOP-C 184). Other applications
      of small SPIO particles include MRI of the bone marrow and the determination of
      perfusion parameters in tumors or other tissues like the myocardium. SPIO
      particles with a modified coat can be used in so-called molecular imaging, such
      as receptor-directed imaging, cell labeling for in-vivo monitoring of cell
      migration, e.g., stem cell labeling, and labeling of gene constructs for
      localization in genetic therapy. In tumor therapy SPIO particles can serve as
      mediators for hyperthermia. SPIO is a powerful MR contrast medium with manifold
      applications ranging from diagnostic imaging to molecular medicine.

PMID- 12811687
TI  - Experimental investigations of image quality in X-ray mammography with a
      conventional screen film system (SFS) and a new full-field digital mammography
      unit (DR) with a-Se-detector.
AB  - PURPOSE: Determination of image quality of a new digital mammography system with
      an a-Se-detector. MATERIAL AND METHOD: Radiograms of the Wisconsin Mammographic
      Random Phantom, Modell 152 A (Radiation Measurements Inc., Wisconsin) were
      acquired using a conventional film screen and a digital system. RESULTS: With the
      conventional film screen system there were detected 191/a 38.2 and with the
      digital mammography 219/a 43.8 of 225 possible details. CONCLUSION: Based on
      these results there is the possibility to replace the conventional film screen
      system by the digital mammography with a-Se-detector--this has to be confirmed in
      further clinical trials.

PMID- 12811688
TI  - [Dose reduction through gridless technique in digital full-field mammography].
AB  - PURPOSE: To determine the role of the scatter grid in digital full-field
      mammography with respect to image quality and dose and to compare the
      experimental results with initial clinical experience. MATERIALS AND METHODS: A
      phantom consisting of 205 fields that enclose gold dots of different thickness
      and size (CD-Mam phantom, Medical Department, Nijmegen, Netherlands) was used for
      digital full-field mammography with the conventional grid module and a special
      gridless module. Four different breast thicknesses were simulated using Plexiglas
      as scatter material. First, the phantom was exposed at the parameter and dose
      settings automatically selected in each experimental setup (with and without
      grid). Subsequently, the phantom was exposed at the different simulated breast
      thicknesses using the gridless module in combination with the parameters
      automatically selected for the grid module. This was followed by a series of
      phantom mammograms obtained with the experimental setup reversed. The 16
      mammograms were evaluated by 3 readers and the results compared considering
      breast thickness, radiation dose, and quality. The gridless module was used for
      preoperative labeling in 16 patients for comparison of mammograms obtained with
      and without a grid. RESULTS: For the same entrance dose used in routine
      mammography, digital mammography without grid is superior to digital mammography
      with grid when performed on simulated thin breasts (Plexiglas less than 3 cm),
      with no difference found when performed on simulated large breasts. The
      advantages of gridless mammography are more pronounced at a markedly reduced
      entrance dose (identical parenchymal dose without and with grid using the dose
      automatically selected for the gridless module). This tendency is confirmed by
      the initial clinical comparison. CONCLUSION: Gridless digital full-field
      mammography has the potential to reduce the dose further, in addition to already
      known mechanisms of dose reduction. However, the gridless system must be adjusted
      (markedly higher "switch-off dose" at the detector) to achieve an overall dose
      reduction since gridless mammography is inferior to grid mammography for
      identical doses at the detector plane.

PMID- 12811689
TI  - [Visualization of microcalcifications on mammographies obtained by digital full
      field mammography in comparison to conventional film-screen mammography].
AB  - PURPOSE: To evaluate the visualization of microcalcifications on mammographies
      obtained by full-field digital mammography (FFDM) in comparison to conventional
      film-screen mammography (FSM). MATERIAL AND METHODS: Forty-seven digital and film
      screen mammographies depicting histologically proven lesions (27 benign, 20
      malignant) were assessed by 4 readers. The images obtained with the different
      systems were comparable in terms of positioning. Maximum time interval between
      film-screen mammography and digital mammography was three months. Using a
      questionnaire, the readers evaluated the number of microcalcifications and their
      subjective conspicuity for FFDM (Senographe 2000D, GE Medical Systems, Milwaukee,
      USA) and FSM. A 7-point scale based on the BIRADS classification was used to
      characterize the calcifications by means of ROC analysis. RESULTS: No
      statistically significant differences were seen between the two types of
      mammography among the readers in assessing the number of microcalcifications. The
      subjective conspicuity of microcalcifications was found to be significantly
      better for digital mammographies. The diagnosis assigned by the readers did not
      show significant differences between the two systems. CONCLUSION: Although the
      subjective conspicuity of microcalcifications was found to be significantly
      better on digital mammography compared to film-screen mammography, there was no
      significant advantage of digital mammography resulting from the higher contrast
      resolution nor a disadvantage in terms of characterization of microcalcifications
      resulting from the lower spacial resolution. The advantages of digital
      mammography (e. g. CAD-systems, archiving, dose reduction) can be used without a
      loss of diagnostic quality.

PMID- 12811690
TI  - [Imaging of the coronary arteries by means of multislice helical CT: optimization
      of image quality with multisegmental reconstruction and variable gantry rotation
      time].
AB  - PURPOSE: To evaluate the potential of multisegmental reconstruction and variable
      gantry rotation time for reducing motion-induced artifacts in coronary artery
      imaging by multislice helical CT. MATERIALS AND METHODS: The data sets of 20
      patients (8 with HR < 60 bpm, 12 with HR > 60 bpm) were analyzed. The patients
      underwent multislice helical CT (Aquilion 8, Toshiba, Otawara, Japan) using the
      following parameters: 0.5 mm slice thickness, 250 mA, 120 kV, pitch of 0.25 and
      variable gantry rotation times of 400, 500, or 600 msec. Images were generated by
      halfscan and multisegmental reconstruction. In 9 coronary segments of each
      patient, the presence and severity of motion artifacts were assessed and graded
      on a scale between 5 (no artifacts) and 1 (heaviest artifacts). RESULTS:
      Diagnostically relevant motion artifacts were rare at low heart rates (< 60 bpm)
      for both types of image reconstruction (4 % of all segments). Higher heart rates
      (> 60 bpm) were associated with an increase in motion artifacts on halfscan
      reconstructions (33% of all segments, p < 0.05) but not on multisegmental
      reconstructions (4% of all segments). At low heart rates mean image quality did
      not differ between multisegmental and halfscan reconstruction (4.28 +/- 0.37 vs.
      4.22 +/- 0.41; p > 0.05), whereas at higher heart rates image quality was better
      for multisegmental reconstruction than for halfscan reconstruction (4.23 +/- 0.47
      vs. 3.11 +/- 0.63; p < 0.05). CONCLUSION: Multisegmental reconstruction with
      variable gantry rotation times suppresses motion artifacts and thus improves
      assessment of the coronary arteries in patients with higher heart rates.

PMID- 12811691
TI  - [Reformation as proposed solution for the problem of sectioning different levels
      with 3He-MRT and HR-CT of the chest].
AB  - PURPOSE: 3He-MRI of the lung has been shown to be a sensitive method for
      functional imaging of the lung. A previous study compared 3He-MRI (coronal
      planes) with CT (transverse planes) by looking for ventilation defects and their
      pathomorphologic correlation. Anatomic structures, such as lobar fissures and
      hilar vessels, were used for orientation, but the reliable assignment of
      ventilation defects to lung segments is problematic. The present work compares
      multiplanar reformations of 3He-MRI and HR-CT, which were generated from planes
      determined by the respective method, and investigates their suitability as a
      solution of this problem. MATERIALS AND METHODS: A total of 16 data sets taken
      from 15 patients with unilateral lung transplantation and one patient with lung
      emphysema were retrospectively evaluated. Transverse planes of 3He-MRI and
      coronal planes of HR-CT were reformatted on an external workstation and images
      evaluated by two readers in consensus. The evaluation searched for ventilation
      defects on 3He-MRI and their corresponding defects on HR-CT. The defects were
      related to anatomic structures, with hilar vessels and tracheobronchial tree
      selected for 3He-MRI reformations and lobar fissures for HR-CT reformations.
      RESULTS: All cases were successfully reformatted and all ventilation defects were
      correctly assigned to anatomic structures. On HR-CT reformations, the lobar
      fissures were partially visible in 12 of 16 cases and completely visible in the
      remaining 4 cases. Since reformation compromises the spatial resolution, the
      reformatted images should be evaluated together with the source images.
      CONCLUSION: Looking at HR-CT and 3He-MRI images and their reformations enables
      the detection of ventilation defects and their assignment to lung segments,
      facilitating the correlation of ventilation defects with a pathomorphologic
      pattern on HR-CT.

PMID- 12811692
TI  - [Morphology of gastrointestinal stromal tumors in advanced stages of the disease:
      baseline findings before chemotherapy with imatinib].
AB  - PURPOSE: Gastrointestinal stromal tumors (GISTs) are rare tumors of the
      gastrointestinal tract with an increasing detection rate due to improved
      differentiating methods in current diagnostic pathology. This study evaluates the
      radiologic characteristics of these neoplasms to discover specific signs leading
      to an earlier diagnosis. MATERIALS AND METHODS: As part of a randomized phase III
      clinical trial of the European Organization for Research and Treatment of Cancer
      (EORTC), 72 patients with advanced stage GIST were treated with the selective
      tyrosine-kinase-inhibitor imatinib (Glivec, Novartis, Switzerland). For initial
      staging, 60 patients underwent MRI and 12 patients underwent CT. RESULTS: GISTs
      are mesenchymal tumors that grow submucosally and exophytically and become
      multiple, nodular or ovoid in the advanced stage. The predominant findings are
      peripheral solid structures with strong contrast enhancement and a central
      necrosis. Metastases are primarily located in the liver, where they appear as
      oval or round, sharply delineated solitary lesions with central necrosis. CT
      demonstrates the primary tumors and local recurrences as nearly isodense with the
      liver. On MRI, the lesions are hypointense on T 1 -weighted sequences and
      hyperintense on T 2 -weighted sequences, compared to the liver. CONCLUSION:
      Immunopathology now enables the exact histologic separation of GISTs from other
      mesenchymal tumors. The radiological morphology is not sufficiently specific to
      differentiate GISTs from other mesenchymal tumors. In view of new therapeutic
      options, cognizance of their typical manifestations is of increasing importance
      for radiologists.

PMID- 12811693
TI  - [MRI of prostate cancer using three different coil systems: image quality, tumor
      detection, and staging].
AB  - PURPOSE: To compare three MRI coil systems in terms of image quality, delineation
      of prostate cancer, and tumor staging. MATERIALS AND METHODS: 49 patients with
      prostate cancer underwent MRI at 1.5 Tesla using a combination of an endorectal
      coil with a phased-array body coil (combination coil) prior to radical
      prostatectomy. Images were reconstructed from the data sets acquired with the
      endorectal coil alone and from those acquired with the combined coil. In
      addition, 19 patients of the study patients were examined with the body phased
      array coil alone without the endorectal coil. The prostate was imaged at a slice
      thickness of 3 mm using axial and coronal T 2 -weighted sequences and an axial T
      1 -weighted sequence. Preoperative analysis of all images acquired was done to
      determine the accuracy of MRI in local staging of prostate cancer. An additional
      retrospective analysis served to compare the different coil systems in terms of
      overall image quality, delineation and localization of the tumor, and criteria
      for local staging of prostate cancer. RESULTS: Preoperative analysis showed MRI
      to have an accuracy of 59 % in local tumor staging. Retrospective coil-by-coil
      analysis demonstrated image quality and tumor delineation to be best for the
      combination coil and the endorectal coil. Regarding the staging criteria for
      transcapsular tumor extension and infiltration of adjacent organs, a significant
      advantage of the combination coil compared to the endorectal coil was identified
      only for the criterion of smooth bulging. In addition, the endorectal coil and
      the combination coil were found to be superior to the body phased-array coil in
      assessing 15 of 17 criteria for local tumor staging but the differences were not
      significant. CONCLUSION: In view of the achieved superior image quality, the
      combination coil or the endorectal coil is the preferred method for staging
      prostate cancer.

PMID- 12811694
TI  - [Quantitative perfusion imaging by multi-slice CT in stroke patients].
AB  - OBJECTIVES: Evaluation of a parametric deconvolution algorithm (DA) in the
      diagnostic assessment of stroke patients by multi- slice spiral computed
      tomography (MS-CT). MATERIAL AND METHODS: 52 patients (age range 34 - 89 years)
      with clinically suspected acute ischemia of one hemisphere and no infarct
      demarcation on plain cerebral CT underwent CT perfusion (CTP), performed on
      average 3.4 hours after the onset of symptoms by using MS-CT (4 x 8 mm scan
      volume). Using a DA-based software module, perfusion images of the cerebral blood
      perfusion (CBP), cerebral blood volume (CBV) and mean transit time (MTT) were
      calculated and assessed by two readers for visually apparent perfusion
      abnormalities. Amount and extension of perfusion disturbances were measured and
      correlated with the outcome. RESULTS: Of 44 patients, in whom perfusion maps
      could be generated, territorial infarction was confirmed by follow-up in 22
      subjects. With a sensitivity of 95 % ischemia could be detected on MTT-maps (CBP
      91 %, CBV 77 %). Specificity was highest (100 %) for CBV-maps. Patients with
      infarction showed significant (p < 0.001) reduction of CBP (10.7 vs. 38.3 ml/100
      ml/min), CBV (1.3 vs. 2.3 ml/100 ml) and prolongation of MTT (12.3 vs. 4.3 s)
      compared to the contralateral hemisphere, whereas in patients without infarction
      no significant changes were found. Extension of CBV reduction showed the best
      correlation (r = 0.82) with final infarct volume. CONCLUSION: The DA-based CTP
      protocol evaluated in this study is a suitable tool for the early identification
      and quantification of acute cerebral ischemia.

PMID- 12811695
TI  - [Sacroiliitis in children with spondyloarthropathy: therapeutic effect of CT
      Guided intra-articular corticosteroid injection].
AB  - PURPOSE: The prospective investigation of the therapeutic effect of CT-guided
      intra-articular corticosteroid injection into inflammatory sacroiliac (SI) joints
      compared to conventional treatment with nonsteroidal anti-inflammatory drugs
      (NSAIDS) in children with juvenile spondyloarthropathy (jSpA) and the
      determination of the role of dynamic magnetic resonance imaging (MRI) in
      establishing the indication and monitoring the therapy. MATERIALS AND METHODS:
      The study comprises 89 children with known jSpA who were diagnosed by MRI to have
      a unilateral or bilateral sacroiliitis. Therapy with NSAIDS was initiated or
      continued in all 89 patients. Four weeks after the diagnostic MRI, two groups
      were distinguished according to the clinical response to NSAIDS, with group 1
      consisting of 33 responders and group 2 of 56 non-responders. The patients of
      group 2 were treated with CT-guided intra-articular corticosteroid injection (low
      dose injection) while the therapy with NSAIDS was continued. A total of 83 SI
      joints were punctured without complications, 27 bilaterally and 29 unilaterally.
      The indication for the intervention was based on inflammatory activity as
      determined by MRI. The therapy was monitored by clinical follow-up every 8 to 12
      weeks over a period of 20 months. Follow-up by dynamic MRI was performed in all
      56 children of group 2 and in 15 of the 33 children of group 1 within 8 +/- 4
      months of the initial examination. RESULTS: A total of 87.5% of the children in
      group 2 showed a statistically significant decrease in their subjective
      complaints from 6.9 +/- 3.4 to 1.8 +/- 1.7 (p < 0.05) as measured on a visual
      analog scale (VAS from 0 to 10). Improvement was seen as early as 1.5 +/- 1.0
      weeks after the intervention and lasted for a mean of 12 +/- 6 months. The
      children in group 1 already showed similar improvement of the VAS from 6.8 +/-
      3.2 to 1.5 +/- 1.4 (p < 0.05) during the initial four weeks of NSAIDS therapy,
      with the improvement lasting for the 20-month observation period. The follow-up
      dynamic MRI (0.1 mmol/kg body weight) during therapy showed a statistically
      significant lower contrast-enhancement in both groups (group 1: 117 +/- 43 %
      versus 38 +/- 24 %, p < 0.05; group 2: 127 +/- 59 % versus 38 +/- 22 %, p <
      0.05). One third of the patients of group 2 showed progression of joint
      destruction despite absence of subjective complaints. CONCLUSION: CT-guided intra
      articular corticosteroid injection has proven an effective, symptomatic, and
      uncomplicated therapy of acute sacroiliitis in patients with jSpA. Dynamic MRI
      has a role in establishing the indication for intervention but its role for any
      follow-up is restricted to cases with inconclusive clinical response.

PMID- 12811696
TI  - [MR angiography of the coronary arteries: comparison of the blood pool contrast
      medium Gadomer and Gd-DTPA in pigs].
AB  - AIM: To investigate the signal-enhancing effects of the macromolecular contrast
      medium Gadomer in MR angiography of the coronary arteries compared to Gd-DTPA.
      MATERIAL AND METHODS: A total of 15 MRI examinations of the heart were performed
      in pigs at 1.5 T using a pulse-triggered, segmented 3D FLASH sequence with data
      acquisition during breathhold before and up to 30 min after contrast medium
      injection. Gadomer was investigated at two doses (0.05 and 0.1 mmol Gd/kg), Gd
      DTPA at one (0.3 mmol Gd/kg) (n = 5 examinations per dose). Standard sequences
      without magnetization preparation were supplemented by sequences with
      magnetization saturation applied before data acquisition before and immediately
      after contrast medium injection. Analysis comprised quantitative determination of
      blood and myocardium signal to noise (S/N) and contrast to noise (C/N) and
      qualitative assessment of several parameters of image quality and coronary artery
      visualization. RESULTS: Gadomer leads to a significant C/N increase between blood
      and myocardium compared to the unenhanced examination and the increase is longer
      lasting than that produced by Gd-DTPA (Gd-DTPA: only directly after injection;
      Gadomer: up to 5 min post injection at 0.05 mmol Gd/kg, up to 10 min at 0.1 mmol
      Gd/kg). The qualitative evaluation shows that visualization of the coronary
      arteries and branch vessels is significantly better with Gadomer at both doses
      than with Gd-DTPA. Magnetization saturation increases the C/N in combination with
      Gd-DTPA and at the higher dose of Gadomer with the latter producing a higher
      increase in C/N values. CONCLUSION: Gadomer is a suitable contrast medium for MR
      angiography of the coronary arteries with the dose of 0.1 mmol Gd/kg being
      superior to 0.05 mmol Gd/kg due to a longer imaging window.

PMID- 12811697
TI  - [Magnetosomes as biological model for iron binding: relaxivity determination with
      MRI].
AB  - PURPOSE: In vitro characterization of iron-containing bacterial particles
      (magnetosomes) as superparamagnetic contrast agents for MRI. MATERIAL AND
      METHODS: Different concentrations of magnetosomes were examined with a 1.5 T
      clinical whole-body MR system at 21 degrees C using the transit/receive extremity
      coil. Both longitudinal and transversal relaxivities (R1 and R2) of the
      magnetosomes were determined by an inversion recovery snapshot gradient recall
      echo (IR FLASH) with various inversion times and a multi echo spin echo sequence.
      Atomic absorption spectrometry (AAS) and electron microscopy were used as
      reference standard. RESULTS: Longitudinal and transverse relaxivities of the
      magnetosomes were calculated to be R1 = 7.688 mmol -1 s -1 and R2 = 147.67 mmol 
      1 s -1, respectively. The corresponding iron concentrations were determined in
      all dilutions using AAS, while the magnetosomes were morphologically delineated
      by electron microscopy. CONCLUSION: Magnetosomes represent a new and interesting
      class of iron-containing contrast agents warranting further evaluation in
      cellular cultures and animal models. Magnetosomes may be suited for displaying
      the vector distribution and gene expression of new molecular therapies.

PMID- 12811698
TI  - [Characterization of focal liver lesions with contrast-enhanced low MI real time
      ultrasound and SonoVue].
AB  - PURPOSE: SonoVue is a new microbubble ultrasound contrast agent that for the
      first time allows continuous real time examination during the different phases of
      contrast enhancement using low transmission power, expressed as mechanical index
      (MI). This study investigates whether low MI real time phase inversion imaging
      with SonoVue can improve the characterization of focal liver lesions in
      comparison to unenhanced sonography and power Doppler sonography. MATERIALS AND
      METHODS: Sixty-three patients with 35 malignant and 28 benign liver lesions were
      studied with unenhanced ultrasound (US) including B-mode and power Doppler,
      followed by contrast-enhanced al MI (0.1 - 0.3) real time phase inversion US
      during arterial, portal-venous and delayed liver phase (> 2 min after injection).
      Findings of the scans obtained before and after administration of contrast agent
      were compared with each other and with reference examinations (biopsy, MRI, CT or
      intraoperative US). RESULTS: The number of correctly diagnosed lesions increased
      from 41 (65%) without contrast agent to 58 (92%) with contrast agent (p < 0.001).
      The differentiation of malignant from benign lesions improved from 43 (68 %) to
      60 (95 %, p < 0.001). After administration of the contrast agent, all 35
      malignant lesions were correctly recognized and 3 of the 28 benign lesions were
      misclassified. All 27 metastases showed little or no enhancement on portal-venous
      and delayed phase imaging, independent of their arterial features. All 6
      hepatocellular carcinomas (HCC) enhanced markedly during arterial phase and 5
      showed less contrast uptake than normal liver in the late phase. Ten of 11
      hemangioma displayed arterial peripheral nodular enhancement followed by
      progressive centripetal fill-in. Nine of 11 focal nodular hyperplasias (FNHs)
      showed profuse arterial enhancement (5 with a transient "spokewheel") and
      contrast uptake similar to normal liver thereafter. One FNH showed a subtle
      central scar. CONCLUSION: Low MI real time US with SonoVue markedly improves the
      characterization of focal hepatic lesions in comparison with unenhanced
      sonography.

PMID- 12811699
TI  - [Feasibility and optimization of the combined injection of contrast medium and
      normal saline with a single-syringe CT injection system].
AB  - PURPOSE: To optimize the technique of injecting contrast medium followed by
      saline flush with a single-syringe CT injection system. MATERIALS AND METHODS: A
      CT injection system with a single syringe was filled with 100 ml of contrast
      medium (Iopromide 300 or Iomeprol 400) and 50 ml of normal saline solution. The
      following variables were evaluated: filling sequence, filling rate, syringe
      position during filling, ejection rate and delay before ejection. In consecutive
      portions of 10 ml, the whole volume was continuously ejected into test tubes that
      were subjected to CT densitometry on these test tubes. Each experiment was
      performed three times. RESULTS: Filling the syringe first with saline solution
      and subsequently with contrast medium resulted in no substantial mixing, whereas
      filling in the reverse order caused noticeable mixing of both solutions. Manual
      filling at a rate < or = 1 ml/s gave the best results. At faster filling rates (4
      ml/s, 10 ml/s), substantial mixing of contrast agent and saline solution was
      observed. The separation of the two liquids was optimal when the syringe nozzle
      was pointed downward. Ejection rate (3 ml/s, 4 ml/s) and time delay between
      filling and ejection (0 min, 10 min) did not influence the distribution of
      density. The maximum iodine concentration using this approach was 235 mg/ml for
      Iopromide 300 and 327 mg/ml for Iomeprol 400. This indicates a reduction of the
      maximum iodine concentration of up to 28 % even when using the optimal technique
      for controlling mixing of both liquids. CONCLUSION: Manual filling of the CT
      injection syringe with saline solution followed by contrast media with the
      syringe nozzle pointed downward provides the best separation between contrast
      medium and normal saline solution but reduces the maximum iodine concentration by
      up to 28 %. For examinations requiring a high iodine concentration, such as CT
      angiography, an iodine concentration of 400 mg/ml should be selected for the
      combined injection of contrast medium and normal saline solution with a single
      syringe CT injection system.

PMID- 12811700
TI  - [Electronic distribution of patient records and images through PACS:
      implementation of data protection at the University Hospital in Freiburg].
AB  - In large installations of a Picture Archiving and Communication System (PACS),
      data protection becomes an issue. Above all, not every employee should have
      access to all data stored in the system. At the Freiburg University Hospital, we
      developed a concept of dynamic assignment of authorization, assuring that every
      physician is authorized to the data of all patients under his care. We describe
      the technical implementation of data protection developed for the integration of
      PACS and electronic patient records in Freiburg. The system was installed in
      January 2001 and the experience of its two years in operation is reported.

PMID- 12811701
TI  - [Successful use of transvenous angio-multidetector-CT in diagnosing cecal
      angiodysplasia as the cause of peranal hemorrhage].

PMID- 12811702
TI  - [CT-controlled bronchoscopic puncture in diagnostic verification of hilar space
      occupying lesion].

PMID- 12811703
TI  - [Solitary carcinoid metastasis in the heart septum: initial diagnosis with CT].

PMID- 12811704
TI  - [Diagnostic biopsy of diffuse splenic infiltration in a patient with non-Hodgkin
      lymphoma].

PMID- 12811705
TI  - Use of CT angiography in patient selection for thrombolytic therapy.
AB  - It has been shown that thrombolytic therapy can improve clinical outcome in some
      patients with acute cerebral ischemia. These patients have been reported to be
      characterized by certain clinical and imaging findings, mainly with non-contrast
      enhanced computed tomography (CT). Our purpose in this study was to find out
      whether CT angiography (CTA) information about the status of the cerebral vessels
      is helpful in the selection of patients who may benefit the most from
      thrombolytic therapy for acvte cerebral ischemia. CTA was prospectively performed
      in 15 consecutive patients (6 women and 9 men; age range 44-83 years) with
      moderate or severe symptoms of hyperacute cerebral ischemia. The clinical
      manifestations of the patient's condition and the findings on CTA were analyzed.
      Three-dimensionally reconstructed CTA images of diagnostic quality could be
      obtained for all 15 patients. Of the 15 patients 14 had a vessel occlusion
      identified on CTA, which was consistent with and/or helpful for making the
      clinical diagnosis in all 14 cases; one patient had an aneurysm of the anterior
      communicating artery without detectable hemorrhage on CTA. Although a
      thrombolytic agent was not given because of CTA evidence of intracranial
      aneurysm, the patient nevertheless developed a massive subarachnoid hemorrhage
      during hospitalization. Ischemic symptoms reversed after CTA and before the
      initiation of thrombolytic therapy in 2 patients whose CTAs showed occlusion of
      secondary branch of the middle cerebral artery (MCA). CTA can provide important
      information before the initiation of thrombolytic therapy. Identification both of
      the occluded vessel and of an intracranial aneurysm is feasible with the use of
      CTA, which is particularly important if the intracranial aneurysm is a potential
      contraindication to thrombolytic therapy. Occlusion of a secondary branch of the
      MCA and internal carotid artery occlusion are valuable prognostic predictors.

PMID- 12811706
TI  - A prospective double-blind study of nasal sumatriptan versus IV ketorolac in
      migraine.
AB  - We conducted a study to compare the efficacy in migraine headache of nasal
      sumatriptan and intravenous ketorolac. The study was a prospective, double-blind
      study done with a convenience sample of 29 patients presenting to the emergency
      department (ED) with acute migraine. Patients received either 20 mg of nasal
      sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of
      their headache on a 100-mm visual analog scale (VAS) of pain prior to medication,
      and again 1 hour after medication. Differences between initial and 1-hour scores
      were analyzed. Before treatment, no difference existed between the groups in the
      intensity of headache. One hour after medication, the sumatriptan group had a
      decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462
      mm on the VAS. The decrease in pain score with ketorolac was significantly
      greater than that with sumatriptan (P < 0.001). The study therefore showed that
      both sumatriptan and ketorolac effectively reduced the pain associated with acute
      migraine headache, but that intravenous ketorolac produced a greater reduction in
      pain than did nasal sumatriptan.

PMID- 12811707
TI  - Minimum clinically significant VAS differences for simultaneous (paired) interval
      serial pain assessments.
AB  - We conducted two studies to determine whether the minimum clinically significant
      difference in the visual analog scale (VAS) for nearly simultaneous and brief
      interval serial assessments of pain is less than that for pain assessment at 20-
      to 30-minute intervals, using a 10-cm VAS. The first study was a blinded,
      randomized, placebo-controlled paired trial comparing the pain of intravenous
      cannulation in both hands (20-minute application of a eutectic mixture of local
      anesthetics v placebo) of study subjects. The second study was a non-blinded,
      randomized, paired trial of different treatments for jellyfish stings. In the
      first study, 37 of 40 subjects indicated that one hand experienced more pain than
      the other. Eleven of these 37 subjects (30%) indicated differences in VAS values
      of 1.0 cm or less, with a minimum value of 0.5 cm. In the second study, for all
      the VAS-based pain comparisons, VAS differences of <or=0.5 cm (other than zero)
      occurred 183 times, and in 171 of these instances (93%) subjects were able to
      recognize that there was a difference. On the basis of these findings, the
      minimum clinically significant VAS difference for paired comparisons that are
      simultaneous or occur within 5 minutes of each other is about 0.5 cm or less.
      This value is less than the 1.3-cm value determined for serial 20- to 30-minute
      pain comparisons. It is likely that other types of pain comparisons may have
      different minimum clinically significant VAS differences.

PMID- 12811708
TI  - Diagnostic utility of echocardiography in patients with suspected pulmonary
      embolism.
AB  - The aim of this study was to investigate the clinical utility of echocardiography
      in the diagnosis of pulmonary embolism (PE). For this, we enrolled 162 patients
      with suspected PE in a prospective study. We evaluated the sensitivity and
      specificity of right ventricular dilatation, the Doppler evidence of pulmonary
      hypertension, and their possible associations. We also calculated the number of
      lung-scan angiography procedures avoided and the number of patients unnecessarily
      treated when echocardiography was included in the diagnostic work-up. The
      sensitivity and specificity of echocardiography ranged between 29 and 52% and
      between 96% and 87%, respectively. Adding echocardiography to the diagnostic
      strategy for PE would avoid about 12 to 28% of lung-scan angiography procedures,
      but would cause inappropriate treatment of 4 to 14% of all treated patients. The
      clinical utility of echocardiography in the diagnosis of PE is limited. The
      reduction in the number of standard diagnostic procedures obtained through its
      use would be counterbalanced by an excess of patients inappropriately treated.

PMID- 12811709
TI  - Emergency vectorcardiographic study of acute aortic dissection.
AB  - There has been no report in the literature of emergency vectorcardiographic study
      in patients with acute aortic dissection. A total of 135 consecutive patients
      with suspected coronary artery disease was studied. On admission to the intensive
      care unit through the emergency service, each patient was given
      electrocardiographic and vectorcardiographic examinations, which were repeated at
      intervals of 24 hours. Fourteen patients (9 type I, 2 type II, and 3 type III
      according to DeBakey's classification) had acute aortic dissection indicated by
      clinical symptoms and proven by angiography. The electrocardiograms all revealed
      abnormal T-wave inversion in limb or precordial leads except 3 patients. Nine
      (64%) of the 14 patients had abnormal length/width (L/W) ratios of the T-loop in
      2 planes of the emergency vectorcardiogram. Two (22%) among these 9 patients died
      of ventricular tachyarrhythmia. The inscription direction of the T-loop showed
      abnormality in 4 (29%) of the 14 patients; 2 (50%) among these 4 patients died of
      ventricular tachyarrhythmia. The de novo occurrence of sustained ventricular
      tachyarrhythmia after emergency cardiac surgery in patients with acute aortic
      dissection has been documented in this report. Furthermore, patients with acute
      aortic dissection who have (1) an abnormal sense of inscription direction of the
      T-loop in at least 1 of either the horizontal or left sagittal plane, and (2) an
      abnormal L/W ratio in at least 2 planes in the preoperational emergency
      vectorcardiogram, have altered ventricular repolarization and thus are at high
      risk of postoperationally unexpected ventricular tachyarrhythmia. This
      information is not available from the electrocardiogram.

PMID- 12811710
TI  - Efficacy of superactivated charcoal administered late (3 hours) after
      acetaminophen overdose.
AB  - The purpose of this study was to investigate the effect of superactivated
      charcoal (SAC) given late after a drug overdose. Acetaminophen was chosen as our
      overdose drug because it has relatively few side effects, serum levels are easily
      attainable and measurable, and it is generally a common drug overdose. Forty-six
      healthy adult volunteers participated in this randomized, controlled study.
      Acetaminophen was administered the morning after an overnight fast. Thirteen
      participants received 2000 mg acetaminophen and the remaining 33 received 3000
      mg. After 3 hours, half of the participants (22 of 46) received 75 g of SAC
      (Requa, Greenwich, CT) orally as a slurry in 8 oz of apple juice. Serum
      acetaminophen levels were measured at 4 and 7 hours after the initial
      acetaminophen administration. There were significantly lower uncorrected and
      corrected acetaminophen levels in the SAC group compared with the control group
      at both 4 and 7 hours after ingesting acetaminophen. This randomized human
      experimental design trial demonstrates some detoxification benefit in
      administering superactivated charcoal 3 hours after an overdose.

PMID- 12811711
TI  - Calming versus sedative effects of intramuscular olanzapine in agitated patients.
AB  - Distinct calming rather than nonspecific sedation is desirable for the treatment
      of acute agitation. In 3 double-blind studies, acutely agitated patients with
      schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were
      treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg),
      haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness
      Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events
      assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar)
      became unarousable. There were no significant between-group differences in ACES
      scores of deep sleep or unarousable at any time across. Excluding asleep
      patients, agitation remained significantly more reduced with olanzapine than
      placebo (P <.05). The incidences of adverse events indicative of sedation were
      not significantly different with olanzapine versus comparators. For the treatment
      of acute agitation associated with schizophrenia, bipolar mania, or dementia,
      intramuscular olanzapine-treated patients experienced no more sedation than
      haloperidol- or lorazepam-treated patients and experienced distinct calming
      rather than nonspecific sedation.

PMID- 12811712
TI  - Secondary contamination of ED personnel from hazardous materials events, 1995
      2001.
AB  - Hazardous materials (hazmat) events pose a health threat not only for those
      individuals in the immediate vicinity of the release (ie, members of the general
      public, on-site first responders, employees), but also for ED personnel (ie,
      physicians and nurses) treating the chemically contaminated victims arriving at
      the hospital. Secondary contamination injuries to ED personnel result when
      exposed victims enter the ED without being properly decontaminated. Data from the
      Agency for Toxic Substances and Disease Registry's Hazardous Substances Emergency
      Events Surveillance System were used to conduct a retrospective analysis on
      hazmat events occurring in 16 states from 1995 through 2001 that involved
      secondary injury to ED personnel. Six events were identified in which 15 ED
      personnel were secondarily injured while treating contaminated victims. The
      predominant injuries sustained were respiratory and eye irritation. Proper victim
      decontamination procedures, good field-to-hospital communication, and appropriate
      personal protective equipment (PPE) use can help prevent ED personnel injuries
      and contamination of the ED.

PMID- 12811713
TI  - The effect of practitioner characteristics on patient pain and embarrassment
      during ED internal examinations.
AB  - The objective was to determine if practitioner characteristics influence
      patients' pain and embarrassment during an emergency department (ED) internal
      pelvic examination (IPE). This prospective, comparative study was performed in an
      urban, university teaching hospital ED with an annual census of 64,000. The study
      population consisted of a convenience sample of patients who required an IPE as
      part of her ED evaluation. Information gathered included patient age and final
      diagnosis, as well as examiner gender and level of training (LOT). Immediately
      after IPE, the patient was asked to rate both pain and embarrassment of the
      examination using a previously validated 100-mm visual analog scale (VAS).
      Finally, each subject was asked to indicate her practitioner gender preference
      for IPE. The influence of examiner gender and LOT on patient pain and
      embarrassment was assessed using a t-test or ANOVA with significance defined as P
      <.05. A total of 278 subjects completed the study (mean age 27.7 +/- 10.5 years,
      range 13 to 70 years). The mean pain and embarrassment scores were 29.7 and 17.5
      respectively. Examiner gender, examiner LOT and patient age did not predict pain
      and embarrassment scores. Overall, 173 (62%) patients had no practitioner gender
      preference, whereas 93 (34%) preferred women and 11 (4%) preferred men.
      CONCLUSION: Examiner characteristics do not influence either the pain or the
      embarrassment associated with IPE in the ED.

PMID- 12811714
TI  - Anticoagulant-induced intramural intestinal hematoma.
AB  - Intramural hematoma of the intestine is a rare complication of anticoagulant
      therapy. We evaluated 7 nontrauma patients with intramural hematoma of the
      intestine diagnosed at our institution between May 1998 and June 2001. All of the
      patients were receiving long-term anticoagulant therapy for previous diseases.
      All 7 patients had abdominal pain, 6 had additional symptoms of nausea and
      vomiting, and 4 had melanotic stools at admission. Six of the patients had
      abnormal coagulation parameters. Both abdominal ultrasonography (US) and
      computerized tomography (CT) showed the exact pathology in all patients. Five of
      the 7 patients were treated, nonoperatively, and the other patients underwent
      surgery. All of the patients were followed with abdominal US and CT (mean 12 =
      months), with complete resolution of their intramural hematomas. Abdominal US and
      CT evaluation performed together will help the accuracy of diagnosis of
      intramural hematoma, but nonoperative therapy is the treatment of choice, with
      surgery indicated if generalized peritonitis or intestinal obstruction develops.

PMID- 12811715
TI  - Diphenhydramine-induced wide complex dysrhythmia responds to treatment with
      sodium bicarbonate.
AB  - Diphenhydramine, a common ingredient in over-the-counter medications, is often
      taken in overdose. Toxicity is usually limited to anticholinergic symptoms.
      However, because diphenhydramine also exhibits type IA sodium channel blockade,
      cardiac toxicity is also possible. Although it would be expected that, like other
      type IA toxicities, diphenhydramine-induced cardiotoxicity could be responsive to
      hypertonic sodium bicarbonate, this finding is largely unappreciated. We describe
      3 cases of diphenhydramine-induced cardiac toxicity that were responsive to
      bicarbonate.

PMID- 12811716
TI  - Bedside ultrasound to determine prandial status.
AB  - The prandial status of ED patients is often unknown. Because a full stomach
      predisposes patients to aspiration during a variety of urgent interventions, a
      method of determining the degree of gastric fullness would be of potential
      clinical importance. The purpose of this single-blind interventional trial was to
      determine if bedside ultrasound, performed by EPs, could accurately determine
      prandial status. We enrolled 20 subjects who were randomized to either a fasting
      or nonfasting group. Three emergency sonographers scanned each subject in both
      the supine and right lateral decubitus (RLD) positions and independently recorded
      their determination of the prandial status both before and after ingestion of
      water. We found that the technique was specific in identifying a full stomach but
      only moderately reliable in identifying an empty one. Best results (sensitivity S
      + 86%, specificity S- 70%, accuracy A+ 78%) were achieved only after water
      ingestion with the patient in the RLD position. We conclude that bedside
      ultrasound is of only limited value for determining prandial states in the ED
      setting.

PMID- 12811717
TI  - A novel use of the endocavity (transvaginal) ultrasound probe: central venous
      access in the ED.
AB  - Use of ultrasound (US) to obtain intravenous access is usually accomplished with
      a 7.5-MHz linear US probe. This paper describes the use of an endocavity US probe
      to obtain vascular access. Since both probes use US of the same megahertz values,
      the picture quality with the two is no different. Because the equipment used for
      each type of probe costs thousands of dollars, the economic value of having to
      purchase one less probe may be significant.

PMID- 12811718
TI  - A current concept of eclampsia.
AB  - Eclampsia is defined by the occurrence of seizures resulting from hypertensive
      encephalopathy on the background of preeclampsia. The development of hypertension
      during pregnancy, a serious and potentially fatal condition, is a leading cause
      of maternal and fetal morbidity and death in the United States.(1-3) It is a
      disease with preventable complications. The pathophysiology of hypertension
      during pregnancy is unclear, but there is consensus that aggressive treatment is
      warranted to prevent complications to both fetus and mother. A current concept of
      pathophysiological character, diagnosis, prevention, and management of eclampsia
      is discussed.

PMID- 12811719
TI  - Use of ultrasound to determine ventricular capture in transcutaneous pacing.
AB  - Determining ventricular capture when using transcutaneous pacing (TCP) can be
      difficult. Our objective was to evaluate the use of ultrasound (US) to determine
      capture in patients undergoing TCP. We studied 15 patients in a convenience
      sample. Videotaped US views were obtained during TCP with concurrent
      electrocardiographic monitoring on the US screen. The treating physician made
      capture determinations first by using clinical indicators, followed by US images.
      Two reviewing physicians blinded to the treating physician's findings and to each
      other determined capture on videotape. Kappa levels of agreement were calculated.
      A value of kappa = 0.84 was found for agreement of the treating physician's
      findings through clinical measures and US. Agreement between the first reviewer
      and the treating physician had kappa =.47 and between the second reviewer and the
      treating physician was had kappa =.67. All P values were <.05. US and clinical
      impression of ventricular capture have good to excellent agreement. US may be
      useful for determining ventricular capture in patients undergoing TCP.

PMID- 12811720
TI  - Unexplained fever in the ED: analysis of 139 patients.
AB  - This study examined consecutive patients with unexplained fever (UF) presenting
      to the ED to define their characteristics and to compare distinctive parameters
      between admitted and discharged patients. During a 3-month period, all adult
      patients presenting to the ED with UF were prospectively followed for 1 month. Of
      139 patients with UF, 58 patients (42%) were admitted to the hospital, whereas 81
      patients (58%) were discharged. Whereas most of the discharged patients had self
      limited febrile disease and eventually recovered, the admitted patients had more
      unresolved fever, serious infections, or systemic diseases and a 5% mortality
      rate. The admitted patients were older, had more comorbidity, higher leukocyte
      count, and anemia, but not a higher degree of fever. Older age, comorbidity,
      leukocytosis, and anemia, but not higher degree of fever, should direct the
      decision toward admission of a patient with UF.

PMID- 12811721
TI  - Diffusion-weighted MRI of intracerebral hemorrhage clinically undifferentiated
      from ischemic stroke.
AB  - This report describes diffusion-weighted MRI findings of some intracerebral
      hemorrhages clinically undifferentiated from ischemic stroke. We treated patients
      with characteristic features of intracerebral hemorrhages that could distinguish
      themselves from ischemic lesion on diffusion-weighted imaging. Therefore, we
      think diffusion-weighted imaging could be an emergency screening tool for
      ischemic stroke as an alternative to computed tomography, and the EP should be
      familiar with the diffusion-weighted imaging findings of intracerebral hemorrhage
      as well as cerebral infarction.

PMID- 12811722
TI  - Pigtail tube drainage in the treatment of spontaneous pneumothorax.
AB  - We report our experience in using pigtail tube drainage in the treatment of
      spontaneous pneumothorax compared with traditional chest tube thoracotomy. One
      hundred two patients were included and analyzed. Fifty patients were treated with
      the pigtail tube and 52 patients were treated with the traditional chest tube.
      The extubation time, mean hospital stay, evacuation rate, and total cost were
      similar without a significant statistical difference. Among the chest tube group,
      15 underwent surgical intervention as a result of delayed resolution and
      hemopneumothorax; and among the pigtail group, 15 had other procedures for
      pneumothorax, including chest tube insertion and surgical intervention. This
      verifies our initial suspicion that the effectiveness of the pigtail drainage
      system is no less than that of the chest tube. Therefore, when considering
      ambulatory ability and good patient compliance, the pigtail tube drainage system
      can be considered as the treatment of choice for spontaneous pneumothorax.

PMID- 12811723
TI  - Lethal oral papaverine overdose.

PMID- 12811724
TI  - 'Idiopathic' pulmonary embolism.

PMID- 12811725
TI  - Postcontusional Kluver-Bucy syndrome.

PMID- 12811726
TI  - Traumatic dislocation of the testis.

PMID- 12811727
TI  - Imperforate hymen: a not-so-hidden diagnosis.

PMID- 12811728
TI  - Primary hyperparathyroidism: acute paranoid psychosis.

PMID- 12811730
TI  - Phonological short-term memory networks following recovery from Landau and
      Kleffner syndrome.
AB  - Landau-Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise
      healthy children, together with spike-wave discharges predominating over superior
      temporal regions and activated by sleep. Although the outcome of language
      abilities is variable, a residual impairment in verbal short-term memory (STM) is
      frequent. This STM deficit might be related to the persistent dysfunction of
      those temporal lobe regions where epileptic discharges were observed during the
      active phase of the disorder. We tested this hypothesis by measuring brain
      activation during immediate serial recall of lists of 4 words, compared to single
      word repetition, using H(2) (15)O positron emission tomography (PET), in 3 LKS
      patients after recovery and in 14 healthy controls. The patients (TG, JPH, and
      DC) had shown abnormally increased or decreased glucose metabolism in left or
      right superior temporal gyrus (STG) at different stages during the active phase
      of their disease. At the time of this study, the patients were 6-10 years from
      the active phase of LKS. Results showed that Patients JPH and DC had impaired
      performance in the STM condition, whereas TG showed near normal performance. PET
      data showed that JPH and DC activated significantly less than controls left and
      right posterior STG. TG, having near normal STM performance, showed increased
      activity in the posterior part of the right STG. These data suggest that impaired
      verbal STM at late outcome of LKS might indeed be related to a persistent
      decrease of activity in those posterior superior temporal gyri that were involved
      in the epileptic focus during the active phase.

PMID- 12811731
TI  - Repetition effects elicited by objects and their contexts: an fMRI study.
AB  - Event-related fMRI responses were recorded during a recognition memory test for
      previously studied visual objects. Some studied objects were superimposed on the
      same context (landscape scenes) as at study, some were superimposed on a
      different studied context, and some were paired with new contexts. Unstudied
      objects were paired with either a studied or a new context. Relative to all other
      stimulus classes, test stimuli where both components were unstudied elicited
      enhanced responses in lateral and ventral extrastriate visual cortex. This
      effect, which is analogous to a previously described electrophysiological result
      obtained with the same experimental procedure, had the same magnitude regardless
      of whether a test item was composed of one or two studied components, or whether
      a single studied component was task relevant or task irrelevant. The findings
      point to the existence of repetition-sensitive neural mechanisms that operate in
      a non-linear manner.

PMID- 12811732
TI  - Relation between brain activation and lexical performance.
AB  - Functional magnetic resonance imaging (fMRI) was used to determine whether
      performance on lexical tasks was correlated with cerebral activation patterns. We
      found that such relationships did exist and that their anatomical distribution
      reflected the neurocognitive processing routes required by the task. Better
      performance on intramodal tasks (determining if visual words were spelled the
      same or if auditory words rhymed) was correlated with more activation in unimodal
      regions corresponding to the modality of sensory input, namely the fusiform gyrus
      (BA 37) for written words and the superior temporal gyrus (BA 22) for spoken
      words. Better performance in tasks requiring cross-modal conversions (determining
      if auditory words were spelled the same or if visual words rhymed), on the other
      hand, was correlated with more activation in posterior heteromodal regions,
      including the supramarginal gyrus (BA 40) and the angular gyrus (BA 39). Better
      performance in these cross-modal tasks was also correlated with greater
      activation in unimodal regions corresponding to the target modality of the
      conversion process (i.e., fusiform gyrus for auditory spelling and superior
      temporal gyrus for visual rhyming). In contrast, performance on the auditory
      spelling task was inversely correlated with activation in the superior temporal
      gyrus possibly reflecting a greater emphasis on the properties of the perceptual
      input rather than on the relevant transmodal conversions.

PMID- 12811733
TI  - The role of age of acquisition and language usage in early, high-proficient
      bilinguals: an fMRI study during verbal fluency.
AB  - We assessed the effects of age of acquisition and language exposure on the
      cerebral correlates of lexical retrieval in high-proficient, early-acquisition
      bilinguals. Functional MRI was used to study Spanish-Catalan bilinguals who
      acquired either Spanish or Catalan as a first language in the first years of
      life. Subjects were exposed to the second language at 3 years of age, and have
      used both languages in daily life since then. Subjects had a comparable level of
      proficiency in the comprehension of both languages. Lexical retrieval with the
      verbal fluency task resulted in the well-established pattern of left hemispheric
      activation centered on the inferior frontal region. The effect of age of
      acquisition was assessed by dividing the subjects into two groups, on the basis
      of the language acquired first (Catalan-born or Spanish-born bilinguals).
      Functional comparisons indicated that less extensive brain activation was
      associated with lexical retrieval in the language acquired earlier in life. The
      two groups were also different in language usage/exposure, as assessed with a
      specific questionnaire; in particular, the exposure to the second language
      (Spanish) was less intensive in the case of Catalans. This was reflected in a
      significant interaction, indicating a more extensive activation in Catalans
      during production in Spanish. Overall, these results indicate that, during a
      production task, both age of acquisition and language exposure affect the pattern
      of brain activation in bilinguals, even if both languages are acquired early and
      with a comparable level of proficiency.

PMID- 12811734
TI  - Regional cerebral blood flow correlations of somatosensory areas 3a, 3b, 1, and 2
      in humans during rest: a PET and cytoarchitectural study.
AB  - The concept of functional connectivity relies on the assumption that cortical
      areas that are directly anatomically connected will show correlations in regional
      blood flow (rCBF) or regional metabolism. We studied correlations of rCBF of
      cytoarchitectural areas 3a, 3b, 1, and 2 in the brains of 37 subjects scanned
      with PET during a rest condition. The cytoarchitectural areas, delineated from 10
      postmortem brains with statistical methods, were transformed into the same
      standard anatomical format as the resting PET images. In areas 3a, 3b, and 1,
      somatotopically corresponding regions were intercorrelated. Area 2 was correlated
      with the dorsal pre-motor area. These results were in accordance with the
      somatosensory connectivity in macaque monkeys. In contrast, we also found
      correlations between areas 3b and 1 with area 4a, and SMA, and among the left and
      right hand sector of areas 3a, 3b, and 1. Furthermore, there were no correlations
      between areas 3b, 1, and 2 with SII or other areas in the parietal operculum, nor
      of other areas known to be directly connected with areas 3a, 3b, 1, and 2 in
      macaques. This indicates that rCBF correlations between cortical areas during the
      rest state only partly reflect their connectivity and that this approach lacks
      sensitivity and is prone to reveal spurious or indirect connectivity.

PMID- 12811735
TI  - Learning networks in health and Parkinson's disease: reproducibility and
      treatment effects.
AB  - In a previous H(2) (15)O/PET study of motor sequence learning, we used principal
      components analysis (PCA) of region of interest (ROI) data to identify
      performance-related activation patterns in normal subjects and patients with
      Parkinson's disease (PD). In the present study, we determined whether these
      patterns predicted learning performance in subsequent normal and untreated PD
      cohorts. Using a voxel-based PCA approach, we correlated the changes in network
      activity that occurred during antiparkinsonian treatment and their relationship
      to learning performance. We found that the previously identified ROI-based
      patterns correlated with learning performance in the prospective normal (P <
      0.01) and untreated PD (P < 0.05) cohorts. Voxel analysis revealed that target
      retrieval was related to a network characterized by bilateral activation of the
      dorsolateral prefrontal, premotor and anterior cingulate cortex, the precuneus,
      and the occipital association areas as well as the right ventral prefrontal and
      inferior parietal regions. Target acquisition was associated with a different
      network involving activation of the caudate, putamen, and right dentate nucleus,
      as well as the left ventral prefrontal and inferior parietal areas.
      Antiparkinsonian therapy gave rise to changes in retrieval performance that
      correlated with network modulation (P < 0.01). Increases in network activation
      and learning performance occurred with internal pallidal deep brain stimulation
      (GPi DBS); decrements in these measures were present with levodopa. Our findings
      suggest that network analysis of activation data can provide stable descriptors
      of learning performance. Network quantification can provide an objective means of
      assessing the effects of therapy on cognitive functioning in neurodegenerative
      disorders.

PMID- 12811737
TI  - In vitro fertilization and polyspermy in the pig: factors affecting fertilization
      rates and cytoskeletal reorganization of the oocyte.
AB  - Polyspermy is a common phenomenon in the pig. Extensive information has become
      available from in vitro studies on not only the quality of oocytes but also the
      quality of spermatozoa. However, little information is available on the relative
      penetration rates of fresh and frozen spermatozoa from the same ejaculate from
      boars of different breeds. The present results, based on a total of 15 boars of
      three different breeds, revealed that the inter-breed variation in fertilization
      and polyspermic rates is larger than intra-breed variation. It was also shown
      that the incidence of polyspermy as well as penetration rate was greatly
      decreased by freezing and thawing, even if a higher number of sperm was
      coincubated with cumulus-free oocytes for a longer period compared to fresh sperm
      of the same ejaculate. This study focuses on the cytoskeletal organization of the
      oocyte with respect to the status of cumulus investment, and monospermic and
      polyspermic fertilization. The status of cumulus cells correlated with the
      density of transzonal cumulus-cell processes and with the maturation rate of
      oocytes and, to some degrees, the incidence of polyspermy. Polyspermic zygotes
      formed multiple microtubule domains in association with individual male pronuclei
      (PN), but in a high degree of polyspermy (more than trispermy), the pronuclear
      apposition did not proceed. The effect of multiple PN of paternal and maternal
      origin on the cytoskeletal reorganization is also discussed.

PMID- 12811738
TI  - How does polyspermy happen in mammalian oocytes?
AB  - Polyspermy is one of the most commonly observed abnormal types of fertilization
      in mammalian oocytes. In vitro fertilization (IVF) provides approaches to study
      the mechanisms by which oocytes block polyspermic fertilization. Accumulated data
      indicate that oocyte, sperm and insemination conditions are all related to the
      occurrence of polyspermic fertilization. A high proportion of immature and aged
      oocytes showed polyspermy as compared with mature oocytes. Preincubation of
      oocytes and/or sperm with oviductal epithelial cells or collected oviductal fluid
      before IVF reduces polyspermic penetration. Recently, it was found that an
      abnormal zona pellucida is one of main causes of polyspermy in human eggs. A high
      proportion of polyspermy has resulted from the use of a high concentration of
      capacitated spermatozoa at the site of fertilization, irrespective of in the in
      vivo or in vitro environment. Oviductal secretions or oviductal epithelial cells
      themselves can regulate the number of spermatozoa reaching or binding to the zona
      pellucida thus reducing multiple sperm penetration. Suboptimal in vitro
      conditions, such as supplementations in IVF media, pH, and temperature during
      IVF, also induce polyspermic fertilization in some mammals. Species-specific
      differences are present regarding the relationship between insemination
      conditions and polyspermy.

PMID- 12811739
TI  - Cellular and molecular mechanisms leading to cortical reaction and polyspermy
      block in mammalian eggs.
AB  - Following fusion of sperm and egg, the contents of cortical granules (CG), a kind
      of special organelle in the egg, release into the perivitelline space (cortical
      reaction), causing the zona pellucida to become refractory to sperm binding and
      penetration (zona reaction). Accumulating evidence demonstrates that mammalian
      cortical reaction is probably mediated by activation of the inositol phosphate
      (PIP(2)) cascade. The sperm-egg fusion, mediated by GTP-binding protein (G
      protein), may elicit the generation of two second messengers, inositol 1,4,5
      triphosphate (IP(3)) and diacylglycerol (DAG). The former induces Ca(2+) release
      from intracellular stores and the latter activates protein kinase C (PKC),
      leading to CG exocytosis. Calmodulin-dependent kinase II (CaMKII) may act as a
      switch in the transduction of the calcium signal. The CG exudates cause zona
      sperm receptor modification and zona hardening, and thus block polyspermic
      penetration. Oolemma modification after sperm-egg fusion and formation of CG
      envelope following cortical reaction also contribute to polyspermy block.

PMID- 12811740
TI  - Perivitelline space: does it play a role in blocking polyspermy in mammals?
AB  - The perivitelline space of mammalian oocytes changes in size and composition
      during preimplantation development. Often overlooked in the past, this space
      contains a hyaluronan-rich extracellular matrix prior to fertilization and a
      cortical granule envelope following release of the cortical granules at
      fertilization. The hyaluronan-containing matrix of unfertilized oocytes is well
      developed in some species such as opossums and humans but is scant in rodents
      including the hamster and mouse. The significance of the hyaluronan-rich matrix,
      which attaches to the plasma membrane of the oocytes, is not fully understood.
      However, hyaluronan, which can inhibit membrane fusion, is present in the
      perivitelline space (PVS) of unfertilized oocytes and must be negotiated by the
      fertilizing sperm. Following fertilization, the cortical granule envelope forms
      as the cortical granules disperse, thereby causing the PVS to increase
      significantly in size. Calcium is important in the dispersion of the cortical
      granules following exocytosis. Once formed, the cortical granule envelope in some
      species is about the same thickness as the zona pellucida, but it is not readily
      visualized unless it is stained with fluorescent probes or examined
      ultrastructurally after following stabilization with ruthenium red. The envelope
      contains proteins that remain in the PVS until the time of blastocyst hatching.
      Although little work has been done on the functions of the cortical granule
      envelope, several studies are consistent with the idea that it plays a role in
      blocking polyspermy. While nicotine increases polyspermy in sea urchins, its
      effects on polyspermy in human smokers have not been characterized, but could be
      addressed in human in vitro fertilization labs.

PMID- 12811741
TI  - Fertilization abnormalities following human in vitro fertilization and
      intracytoplasmic sperm injection.
AB  - Fertilization abnormalities are commonly encountered following in vitro
      fertilization. The widespread introduction of assisted fertilization methods has
      rapidly led to a changes in both the incidence and types of these aberrations.
      Such abnormalities can be identified by careful morphological evaluation at the
      early zygote stage, of pronuclei as well as of polar body formation, and may be
      confirmed by cytogenetic assessment. The recognition and understanding of
      fertilization abnormalities have led to the development of novel techniques aimed
      at preventing them, as well as recent bold attempts at correction. Removal of one
      pronucleus may allow some triploid embryos to revert to a normal diploid stage.
      These new developments should provide insight into the understanding of
      parthenogenesis, androgenesis, and gynogenesis in the human. Microsc. Res. Tech.
      61:358-361, 2003.

PMID- 12811742
TI  - Interactions of sperm perinuclear theca with the oocyte: implications for oocyte
      activation, anti-polyspermy defense, and assisted reproduction.
AB  - Perinuclear theca (PT) is the cytoskeletal coat of mammalian sperm nucleus that
      is removed from the sperm head at fertilization. PT harbors the sperm borne,
      oocyte-activating factor (SOAF), a yet-to-be-characterized substance responsible
      for triggering the signaling cascade of oocyte activation, thought to be
      dependent on intra-oocyte calcium release. The present article reviews the
      current knowledge on the biogenesis and molecular composition of sperm PT.
      Possible functions of sperm PT during natural and assisted fertilization, and in
      the initiation of embryonic development are discussed. Furthermore, evidence is
      provided that SOAF is transferred from the sperm PT to oocyte cytoplasm through
      the internalization and rapid solubilization of the post-acrosomal PT. It is
      shown that during natural fertilization the sperm PT dissolves in the oocyte
      cytoplasm concomitantly with sperm nuclear decondensation and the initiation of
      pronuclear development. SOAF activity is preserved in the differentially
      extracted sperm heads only if the integrity of PT is maintained. After
      intracytoplasmic sperm injection (ICSI), activation occurs only in those oocytes
      in which the injected spermatozoon displays complete or partial dissolution of
      PT. In the latter case, the residual PT of the sub-acrosomal and/or post
      acrosomal sperm region may persist on the apical surface of the sperm
      nucleus/male pronucleus and may cause a delay or arrest of zygotic development.
      We propose that the sperm PT harbors SOAF in the post-acrosomal sheath, as this
      is the first part of the sperm cytosol to enter the oocyte cytoplasm and its
      disassembly appears sufficient to initiate the early events of oocyte activation.
      Dissolution of the sub-acrosomal part of the PT, on the other hand, appears
      necessary to insure complete DNA decondensation in the internalized sperm nucleus
      and initiate DNA synthesis of both pronuclei. The release of the SOAF from the
      sperm head into oocyte cytoplasm at fertilization ultimately leads to the
      activation of oocyte mechanism including the completion of the meiotic cell
      cycle, pronuclear development and anti-polyspermy defense.

PMID- 12811743
TI  - Polyspermy prevention in marine invertebrates.
AB  - In marine invertebrates, as in most other organisms, normal development requires
      that only one sperm nucleus joins with the egg nucleus at fertilization. The
      principal mechanisms employed are (1) prevention of sperm-egg plasma membrane
      fusion and (2) modifications of the egg extracellular coat to prevent sperm
      binding and/or penetration. In a third strategy, fertilization is polyspermic,
      but only one sperm nucleus fuses with the egg nucleus. Other factors such as
      gamete density during spawning, chemotaxis, and localized sites for sperm entry
      may also affect the numbers of sperm reaching the egg.

PMID- 12811744
TI  - The relationship between BCL6 bodies and nuclear sites of normal and halogenated
      DNA and RNA synthesis.
AB  - BCL6 is a POZ/BTB and zinc finger transcription factor that self-interacts and
      accumulates into discrete nuclear "bodies" of unknown function. We recently
      reported that BCL6 bodies associate with bromodeoxyuridine (BrdU)-substituted
      DNA, suggesting their implication in replication. To examine this possibility, we
      examine here by electron and confocal microscopy the relation between BCL6 bodies
      and replication foci (RF) using incorporation of various halogenated nucleotides
      (BrdU, chlorodeoxyuridine, CldU, and iododeoxyuridine, IdU) or PCNA
      (proliferating cell nuclear antigen) staining. We show that BCL6 bodies are found
      associated with RF, as revealed by PCNA staining. However, such association is
      markedly prolonged upon BrdU or CldU incorporation, but less, or not at all, upon
      IdU incorporation. Pulse-chase and double-labeling experiments indicate that IdU
      substituted DNA leaves BCL6 bodies after a few tenths of minutes while BrdU- or
      CldU-substituted DNA stalls in their vicinity for several hours, thereby giving
      the characteristic "crowns" of DNA entirely surrounding BCL6 bodies. In all
      cases, however, the halogenated DNA ends up undergoing a movement from BCL6
      bodies toward nucleoplasm and nuclear periphery to reach euchromatin and
      heterochromatin, respectively. We propose that replicating DNA is prone to be
      bound by BCL6, while BrdU/CldU incorporation increases this propensity possibly
      because these two events have synergistic effects on the structure and
      chromatinisation of the newly synthesized DNA. Finally, despite the known
      proximity between nuclear sites of transcription and replication, we show via
      several approaches that BCL6 bodies do not appear to be involved either in RNA
      synthesis or storage.

PMID- 12811745
TI  - Electrospray mass spectrometric study of anionic complexes of enkephalins with
      Cu(II): regioselective distinction of Leu/Ile at the C-terminus induced by metal
      reduction.
AB  - The yield of metallation of methionine-enkephalin and leucine-enkephalin isomers
      by copper(II) chloride was investigated by electrospray ionization ion trap mass
      spectrometry (ESI-ITMS) in negative ionization mode. Binary ([(M-3H)+Cu(II)](-))
      and ternary ([(M-3H)+Cu(II)Cl](-)) complexes were observed. Soft and hard
      desolvation conditions (by changing the declustering voltage) were applied to
      study their influence on the metallation yield and on the observed deprotonated
      and metallated species. Structures of the binary complexes with defined charge
      locations are proposed, based on the observed in-source fragmentations. It was
      demonstrated that the in-source fragmentations under hard desolvation conditions
      could differentiate the Leu/Ile isomers if located at the C-terminal position but
      not at the N-terminal position. This behavior was also observed using a triple
      quadrupole analyzer. This facile distinction, due to a different radical loss
      from the [(M-3Hbond;CO(2))+Cu(II)](-) species (loss of [C(3)H(7)](.) for YGGFL
      and [C(2)H(5)](.) for YGGFI), was facilitated by the reduction of the oxidation
      state of Cu(II). This in-source differentiation of YGGFI and YGGFL was also
      implemented in LC/ESI-MS analysis by post-column addition of the copper salt with
      a syringe pump.

PMID- 12811746
TI  - Nano-high-performance liquid chromatography in combination with nano-electrospray
      ionization Fourier transform ion-cyclotron resonance mass spectrometry for
      proteome analysis.
AB  - Fourier transform ion-cyclotron resonance (FTICR) mass spectrometry offers
      several advantages for the analysis of biological samples, including excellent
      mass resolution, ultra-high mass measurement accuracy, high sensitivity, and wide
      mass range. We report the application of a nano-HPLC system coupled to an FTICR
      mass spectrometer equipped with nanoelectrospray source (nano-HPLC/nano-ESI
      FTICRMS) for proteome analysis. Protein identification in proteomics is usually
      conducted by accurately determining peptide masses resulting from enzymatic
      protein digests and comparing them with theoretically digested protein sequences
      from databases. A tryptic in-solution digest of bovine serum albumin was used to
      optimize experimental conditions and data processing. Spots from Coomassie Blue
      and silver-stained two-dimensional (2D) gels of human thyroid tissue were
      excised, in-gel digested with trypsin, and subsequently analyzed by nano
      HPLC/nano-ESI-FTICRMS. Additionally, we analyzed 1D-gel bands of membrane
      preparations of COS-6 cells from African green monkey kidney as an example of
      more complex protein mixtures. Nano-HPLC was performed using 1-mm reverse-phase C
      18 columns for pre-concentration of the samples and reverse-phase C-18 capillary
      columns for separation, applying water/acetonitrile gradient elution conditions
      at flow rates of 200 nL/min. Mass measurement accuracies smaller than 3 ppm were
      routinely obtained. Different methods for processing the raw data were compared
      in order to identify a maximum number of peptides with the highest possible
      degree of automation. Parallel identification of proteins from complex mixtures
      down to low-femtomole levels makes nano-HPLC/nano-ESI-FTICRMS an attractive
      approach for proteome analysis.

PMID- 12811747
TI  - Preliminary study of the stability of calix[4]arene crown compounds under
      radiolysis.
AB  - The extraction of (135)Cs from high activity waste arising from reprocessing of
      spent fuel can be achieved by using calix[4]arene crown compounds. The radiolytic
      degradation of calix[4]arene crowns as well as their solvent, o-nitrophenyloctyl
      ether (NPOE), was studied using electrospray ionization mass spectrometry (ESI
      MS) (that formed Cs(+) or Na(+) adducts) in nitric acid, as well as by chemical
      ionization tandem mass spectrometry (MS/MS) experiments. The structures of major
      degradation products were identified with MS and specifically labelled nitric
      acid. Although NPOE and calix[4]arene crowns alone are relatively stable, under
      simulated conditions resembling the real industrial processes involving
      radiolysis in the presence of nitric acid, several products resulting from
      nitration and oxidation were observed.

PMID- 12811749
TI  - Extension of the GOOD assay for genotyping single nucleotide polymorphisms by
      matrix-assisted laser desorption/ionization mass spectrometry.
AB  - Over the past years several methods using mass spectrometry for high-throughput
      genotyping of single nucleotide polymorphisms (SNPs) have been developed. Most of
      these procedures require stringent purification. Only the GOOD assay does not
      need any sample purification. Here, several new implementations of this assay are
      presented. The molecular biological procedure of the GOOD assays is based on the
      principle that the analysis of DNA by matrix-assisted laser desorption/ionization
      (MALDI) is strongly dependent on the charge state. A 100-fold increase in
      sensitivity can be achieved if the analyzed DNA product is conditioned by a
      chemical procedure termed 'charge-tagging'. The GOOD assay starts with a PCR;
      allele-specific DNA molecules are generated by extension of modified primers.
      These contain up to three phosphorothioates and optionally a quaternary ammonium
      charged group with ddNTPs or alpha-S-ddNTPs. Then the unmodified part of the
      primers is digested by phosphodiesterase II and the negative charges of the
      phosphorothioates are neutralized by an alkylation reaction resulting in charge
      tagged DNA products. Through the use of a novel DNA polymerase for the primer
      extension, which preferably incorporates ddNTPs over dNTPs, an enzymatic
      degradation of residual dNTPs from the PCR is not required. Additionally, the
      unique property of charge-tag technology is demonstrated to detect specifically
      on the same sample allele-specific DNA products carrying a positive charge-tag in
      the positive ion mode while products carrying a negative charge-tag are analyzed
      in the negative ion mode. We also generated zwitterionic allele-specific products
      that were detectable with high sensitivity in positive ion mode. The findings of
      this study raise interesting questions about the ionization process of nucleic
      acids in MALDI. The new variations of the GOOD assay were applied to genotype
      SNPs of a candidate gene for cardiovascular disease.

PMID- 12811748
TI  - Identification of phytoestrogens in bovine milk using liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - In an international context of promoting scientific research on food safety, the
      interest in molecules having potential hormonal disrupting effects is growing.
      While industrial endocrine disruptors (phthalates, alkylphenols, PCBs, etc.) have
      been studied for several years, natural compounds like phytoestrogens remain less
      investigated. Accordingly, a research project was initiated with its main
      objectives to develop efficient analytical methods for a wide range of
      phytoestrogens in various food matrices, and to evaluate their occurrence in food
      products. Electrospray ionization with tandem mass spectrometric (MS/MS) analysis
      of isoflavones (genistein, daidzein, equol, formononetin, biochanin A), lignans
      (enterolactone, enterodiol), and coumestans (coumestrol) was investigated. This
      study revealed the formation of a large number of fragment ions in both positive
      and negative modes, corresponding to specific cleavages of the hydroxyl,
      carbonyl, and/or methoxy groups, and to Retro-Diels-Alder reactions. An LC/ESI
      MS/MS method was developed consistent with the 2002/657/EC European decision
      criteria. An extraction and clean-up method was developed for milk samples. The
      identification limit for the proposed method appears to be under 1 ng/mL. The
      developed methodology was applied to various milk samples, and the occurrence of
      isoflavones (particularly equol) was demonstrated in the concentration range 1-30
      ng/mL. The efficiency of the proposed analytical method permitted evaluation of a
      new and promising approach to a global risk assessment of natural estrogenic
      active substances including phytoestrogens and their metabolites.

PMID- 12811750
TI  - Protein abundance quantification in embryonic stem cells using incomplete
      metabolic labelling with 15N amino acids, matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry, and analysis of relative
      isotopologue abundances of peptides.
AB  - An isotope dilution method for protein quantification is presented in the context
      of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOFMS) and mass fingerprinting experiments, revealing an unappreciated
      high reproducibility and accuracy of relative peak intensity measurements.
      Labelled proteins were generated by growing cells in a medium containing (15)N
      enriched amino acids, and were mixed with proteins of natural isotopic
      composition from control cells in ratios of approximately 0:1, 1:7, 1:2, 2:1,
      7:1, and 1:0 (labelled/unlabelled). Mixtures were separated by two-dimensional
      gel electrophoresis and analysed by MALDI-TOFMS using typical experimental
      conditions. A linear relationship is demonstrated between the relative
      isotopologue abundances (RIA values) for particular peaks in the isotopic
      distribution of tryptic peptide fragments of the proteins, and the mole fractions
      of labelled proteins in the mixture. Analysis of RIA values (ARIA quantification)
      for peptides of six typical silver-stained protein spots for the various mixtures
      could reproduce the experimentally contrived ratios with approximate errors
      between 4% (2:1 mixture) and about 18% (1:7 mixture). A consideration of error
      and its propagation is discussed. ARIA does not require complete separation of
      the isotope patterns of labelled and unlabelled peptides, and is therefore
      advantageous in combination with all kinds of labelling experiments in biological
      systems, because it is compatible with minimal metabolic incorporation of
      labelling reagent. Simulations indicate that the minimum required (15)N
      enrichment of the total amino acid pool sufficient for ARIA is less than 4%. In
      an accompanying paper in this issue, we apply ARIA to proteins differentially
      labelled with isotope-coded alkylation reagents.

PMID- 12811751
TI  - Analysis of relative isotopologue abundances for quantitative profiling of
      complex protein mixtures labelled with the acrylamide/D3-acrylamide alkylation
      tag system.
AB  - The new method of analysis of relative isotopologue abundances (ARIA) applied
      here is based on the evaluation of total isotope patterns of tryptic protein
      fragments measured by matrix-assisted laser desorption/ionisation time-of-flight
      mass spectrometry (MALDI-TOFMS) to calculate the mixing ratios of composites
      consisting of stable isotope labelled and isotopically natural (unlabelled)
      proteins, as described in an accompanying paper in this issue. Recently, Sechi
      (Rapid Commun. Mass Spectrom. 2002; 16: 1416-1424) and Gehanne et al. (Rapid
      Commun. Mass Spectrom. 2002; 16: 1692-1698) introduced the use of differential
      quantitative mass analysis by MALDI-TOFMS using mixtures of standard proteins
      alkylated prior to two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      with either acrylamide (AA) or deuterium-labelled [2,3,3'-D(3)]-acrylamide
      (D3AA). In the present study we validate the AA/D3AA system, firstly by measuring
      the yield of proteins alkylated with AA, and secondly by using differential
      radioactive labels ((125)I and (131)I) to quantitatively establish that non
      comigration in 2D-PAGE is negligible. ARIA is then applied to quantitatively
      estimate the relative proportions of peptides labelled with AA or D3AA in the
      validated system, using typical silver-stained 2D-PAGE protein spots from 2D gels
      loaded with 150 microg of total liver protein. The precision and limitations of
      ARIA quantification of peptides differentially alkylated with isotopomeric
      reagents are discussed.

PMID- 12811752
TI  - The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer's
      disease: evidence of a novel carboxyterminally elongated Abeta peptide.
AB  - The patterns of amyloid beta (Abeta) peptides in human cerebrospinal fluid (CSF)
      and brain homogenates were studied by surface-enhanced laser
      desorption/ionization (SELDI) time-of-flight (TOF) mass spectrometry, and the
      results were compared with those obtained by Abeta-SDS-PAGE/immunoblot. Apart
      from the peptides known in the literature to occur in the CSF, we postulate the
      existence of a novel, previously not described peptide, either Abeta1-45 or
      Abeta2-46. This peptide was observed exclusively in a pool of samples originating
      from patients with AD, i.e. CSF and postmortem brain homogenates, but not in
      either the pooled CSF samples nor the pooled brain homogenates of the non
      demented controls. Similarly to our previous results, Abeta1-42 was decreased in
      the CSF in AD. Expectedly, brain homogenates of the control subjects did not show
      the presence of Abeta peptides. Compared with Abeta-SDS-PAGE/immunoblot, SELDI
      TOF enabled more precise analysis of Abeta peptides in the human material. We
      conclude that SELDI-TOF offers a promising tool for dementia expression pattern
      profiling using a minute amount of a biological sample.

PMID- 12811753
TI  - ESI-MS/MS analysis of underivatised amino acids: a new tool for the diagnosis of
      inherited disorders of amino acid metabolism. Fragmentation study of 79 molecules
      of biological interest in positive and negative ionisation mode.
AB  - The diagnosis of inherited disorders of amino acids (AA) metabolism is usually
      performed on automated analysers by ion-exchange chromatography and
      quantification after ninhydrin derivatisation of about 50 different AA. A single
      run liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for these
      molecules can be an alternative to this time-consuming technique. The first step
      of this development is the infusion study of the fragmentation of 79 molecules of
      biological interest in electrospray ionisation tandem mass spectrometry (ESI
      MS/MS), in positive and in negative ionisation mode. Among them, three molecules
      can be detected only in negative ionisation mode, 38 only in positive mode and 38
      in the two modes. All the most abundant fragmentations are presented, with
      optimisation of the MS/MS parameters. The positive ionisation mode was retained
      for the simultaneous analysis of 76 molecules. One sensitive and/or specific
      transition is proposed for the monitoring of each molecule. Improvement in
      sensitivity of detection was obtained with the use of an acidic mobile phase.
      Flow injection analysis studies led us to highlight a number of interferences-due
      to isobaric molecules, to in-source collision-induced dissociation, or to natural
      isotopic distribution of the elements-which are listed. For a reliable
      quantification method, these molecules have to be separated by LC before analysis
      in the tandem mass spectrometer. Ion-pairing reversed-phase liquid chromatography
      (RPLC) using perfluorinated carboxylic acids as ion-pairing agents has already
      been found suitable for analysis of AA in MS/MS positive ionisation mode and is
      under development.

PMID- 12811754
TI  - Reconstruction of the isotopic history of animal diets by hair segmental
      analysis.
AB  - Carbon and nitrogen isotope signatures (delta(13)C and delta(15)N) of animal
      tissues provide information about the diet and, hence, the environment in which
      the animals are living. Hair is particularly useful as it provides a stable
      archive of temporal (e.g. seasonal) fluctuations in diet isotope composition. It
      can be sampled easily and with minimal disturbance from living subjects. However,
      derivation of the temporal record along the hair length may be subject to errors
      and uncertainties. This study investigates (and suggests means to minimize)
      several sources of error, including (a) incomplete sampling, (b) sampling during
      the quiescent (telogen) phase, (c) non-representative sub-sampling, (d) ignorance
      of hair growth rate, i.e. time-position relationship of isotope signatures, and
      (e) non-optimal compromise between analytical/procedural precision and
      effort/cost. Cattle tail switch hair was collected from animals of different
      breed, sex and age. Hair was washed, sectioned, and 5- or 10-mm-long sections
      were analyzed for C and N isotope composition. Signatures along paired hairs were
      similar (r(2) approximately 0.8) and distances between isotopic minima and maxima
      nearly identical, indicating that a single hair constituted a representative
      sample and (except for telogen hair) hair growth rate was the same for paired
      hairs. However, cutting hair, instead of plucking, caused a variable loss of
      recently grown hair and information. Telogen hair was identified and data loss
      due to cutting error reduced when more than one hair from the same animal and
      sampling region was compared to spot and delimit common and missing regions.
      Similarly, comparison of isotopic profiles from hair collected at different times
      identified the segment produced during the respective interval and allowed
      calculation of average hair growth rate, which varied between animals (0.69-1.06
      mm d(-1)). Analysis of alternate 10-mm-long sections for two hairs per animal
      provided a good compromise between precision/resolution and effort. The method
      should be applicable to other mammalian species including man.

PMID- 12811755
TI  - Fast high-precision on-line determination of hydrogen isotope ratios of water or
      ice by continuous-flow isotope ratio mass spectrometry.
AB  - A new fast high-precision on-line technique is described for the determination of
      hydrogen isotope ratios of water by continuous-flow mass spectrometry. For the
      first time H(2)/H(2)O-equilibration using a platinum catalyst has been used in a
      fully continuous process. A significant reduction in the H(2)/H(2)O-equilibration
      time is achieved by a complete vaporization of the water and by increasing the
      exchange temperature to 100 degrees C. The analysis time is only approximately 5
      min/sample which includes equilibration and processing. Measurement precision and
      accuracy are better than 1 per thousand and sample consumption is only
      approximately 5 microL. This new technique allows the measurement of a wide range
      of aqueous samples either in a semi-continuous way (discrete samples are injected
      one after another) or in a fully continuous way. This allows us, for the first
      time, to make continuous measurements of ice cores.

PMID- 12811756
TI  - Cluster chemical ionization for improved confidence level in sample
      identification by gas chromatography/mass spectrometry.
AB  - Upon the supersonic expansion of helium mixed with vapor from an organic solvent
      (e.g. methanol), various clusters of the solvent with the sample molecules can be
      formed. As a result of 70 eV electron ionization of these clusters, cluster
      chemical ionization (cluster CI) mass spectra are obtained. These spectra are
      characterized by the combination of EI mass spectra of vibrationally cold
      molecules in the supersonic molecular beam (cold EI) with CI-like appearance of
      abundant protonated molecules, together with satellite peaks corresponding to
      protonated or non-protonated clusters of sample compounds with 1-3 solvent
      molecules. Like CI, cluster CI preferably occurs for polar compounds with high
      proton affinity. However, in contrast to conventional CI, for non-polar compounds
      or those with reduced proton affinity the cluster CI mass spectrum converges to
      that of cold EI. The appearance of a protonated molecule and its solvent cluster
      peaks, plus the lack of protonation and cluster satellites for prominent EI
      fragments, enable the unambiguous identification of the molecular ion. In turn,
      the insertion of the proper molecular ion into the NIST library search of the
      cold EI mass spectra eliminates those candidates with incorrect molecular mass
      and thus significantly increases the confidence level in sample identification.
      Furthermore, molecular mass identification is of prime importance for the
      analysis of unknown compounds that are absent in the library. Examples are given
      with emphasis on the cluster CI analysis of carbamate pesticides, high explosives
      and unknown samples, to demonstrate the usefulness of Supersonic GC/MS (GC/MS
      with supersonic molecular beam) in the analysis of these thermally labile
      compounds. Cluster CI is shown to be a practical ionization method, due to its
      ease-of-use and fast instrumental conversion between EI and cluster CI, which
      involves the opening of only one valve located at the make-up gas path. The ease
      of-use of cluster CI is analogous to that of liquid CI in ion traps with internal
      ionization, and is in marked contrast to that of CI with most other standard
      GC/MS systems that require a change of the ion source.

PMID- 12811757
TI  - Feasibility of atmospheric pressure desorption/ionization on silicon mass
      spectrometry in analysis of drugs.
AB  - The feasibility of atmospheric pressure desorption/ionization on silicon mass
      spectrometry (AP-DIOS-MS) for drug analysis was investigated. It was observed
      that only compounds with relative high proton affinity are efficiently ionized
      under AP-DIOS conditions. The limits of detection (LODs) achieved in MS mode with
      midazolam, propranolol, and angiotensin II were 80 fmol, 20 pmol, and 1 pmol,
      respectively. In MS/MS mode the LODs for midazolam and propranolol were 10 fmol
      and 5 pmol, respectively. The good linearity (r(2) > 0.991), linear dynamic range
      of 3 orders of magnitude, and reasonable repeatability showed that the method is
      suitable for quantitative analysis.

PMID- 12811758
TI  - Cluster ions of diquat and paraquat in electrospray ionization mass spectra and
      their collision-induced dissociation spectra.
AB  - Cluster ions such as [Cat+X+nM](+) (n = 0-4); [Cat-H+nM](+) (n = 1-3); and [2(Cat
      H)+X+nM](+) (n = 0-2), where Cat, X, and M are the dication, anion, and neutral
      salt (CatX(2)), respectively, are observed in electrospray ionization (ESI) mass
      spectrometry of relatively concentrated solutions of diquat and paraquat.
      Collision-induced dissociation (CID) reactions of the clusters were observed by
      tandem mass spectrometry (MS/MS), including deprotonation to form [Cat-H](+), one
      electron reduction of the dication to form Cat(+.), demethylation of the paraquat
      cation to form [Cat-CH(3)](+), and loss of neutral salt to produce smaller
      clusters. The difference in acidity and reduction power between diquat and
      paraquat, evaluated by thermodynamical estimates, can rationalize the different
      fractional yields of even-electron ([Cat-H](+) and its clusters) and odd-electron
      (mostly Cat(+)) ions in ESI mass spectra of these pesticides. The [Cat+n.
      Solv](2+) doubly charged cluster ions, where n <or= 2 and Solv is the solvent
      molecule (methanol and/or water), are only observed as very weak peaks in
      precursor ion CID spectra of the Cat(2+) salt cation at low collision energy. The
      presence of an anion and a solvent molecule in a cluster is assumed to be related
      to existence of tight and loose ion pairs, respectively, in multiply charged
      droplets/ions formed by ESI. The results emphasize again the role of solution
      chemistry concepts such as acidity/basicity, redox power, and ion-pair formation,
      for ESI.

PMID- 12811759
TI  - Quantification of isoflavones and lignans in serum using isotope dilution liquid
      chromatography/tandem mass spectrometry.
AB  - Phytoestrogens (isoflavones and lignans) are receiving increasing attention due
      to a potential protective effect against a number of complex diseases. However,
      in order to investigate these associations, it is necessary to accurately
      quantify the levels of phytoestrogens in foods and biological fluids. We report
      an assay for three isoflavones (daidzein, genistein, and glycitein), two
      metabolites of daidzein (O-desmethylangolensin and equol), and two lignans
      (enterodiol and enterolactone) in human serum using electrospray ionisation
      liquid chromatography/mass spectrometry (LC/MS) with selective reaction
      monitoring. A simple, highly automated sample preparation procedure requires only
      200 microL of sample and utilises one solid-phase extraction stage. Limits of
      detection are in the region of 10 pg/mL for all analytes except equol, which had
      a limit of detection of approximately 100 pg/mL. The method developed is suitable
      for measuring the concentrations of phytoestrogens in blood samples collected
      from large epidemiological studies. The results of the analysis of serum samples
      from 300 men and women living in the UK are reported.

PMID- 12811760
TI  - Analysis of high mass peptides using a novel matrix-assisted laser
      desorption/ionisation quadrupole ion trap time-of-flight mass spectrometer.
AB  - A novel matrix-assisted laser desorption/ionisation quadrupole ion trap time-of
      flight (MALDI QIT ToF) mass spectrometer has been used to analyse high mass
      peptide ions exceeding 2000 Da. Human adrenocorticotropic hormone (fragment 18
      39) and oxidised bovine insulin chain B were utilised to evaluate the performance
      of the instrument both in MS and in MS/MS mode. Its ability to efficiently
      isolate ions and to fragment them using collisionally activated decomposition
      (CAD) has been demonstrated using mixtures diluted to the low-femtomole level on
      target. Additionally, multiple stage mass spectrometry (MS/MS/MS) provides a
      second-generation product ion spectrum in which new fragment ions are detected
      and new stretches of amino acids are identified.

PMID- 12811761
TI  - Sequencing of bacitracin A and related minor components by liquid
      chromatography/electrospray ionization ion trap tandem mass spectrometry.
AB  - A selective reversed-phase liquid chromatography/mass spectrometry (LC/MS(n))
      method is described for the characterization of related compounds in commercial
      bacitracin samples. Mass spectral data for these polypeptide antibiotics were
      acquired on a LCQ ion trap mass spectrometer equipped with an electrospray
      ionization probe operated in the positive and negative ion mode. The LCQ ion trap
      is ideally suited for the sequencing of those linear side-chain cyclized peptides
      because it provides on-line LC/MS(n) capability. Using this method bacitracin A,
      1-epibacitracin A, bacitracins B(1), B(2), B(3) and bacitracin F were sequenced
      and previous sequencing was confirmed. Bacitracins C(1), C(2), C(3), D, H(2) and
      H(3) were resolved chromatographically and their ring portion was sequenced for
      the first time. Four components not described in the literature (1-epibacitracin
      B(1), 1-epibacitracin B(2), 1-epibacitracin C(1) and H(4)) were sequenced
      completely for the first time. The main advantage of this hyphenated LC/MS(n)
      technique is the characterization of the related substances without time
      consuming isolation and purification procedures.

PMID- 12811762
TI  - Application of mass spectrometric techniques for structural analysis of apigenin
      8-C-(6"-O-glucopyranosyl) glucopyranoside--a novel flavonoid C-diglycoside.

PMID- 12811763
TI  - Contributions of insect research toward our understanding of neurosecretion.
AB  - The process of neurosecretion is an important and widespread method of biological
      communication among animals. Although insects and vertebrates appear to be very
      different, neurosecretory mechanisms and the neuropeptides themselves are often
      the same. The gradual acceptance of neurosecretion as a biological phenomenon,
      largely as a result of research done with insects, is discussed.

PMID- 12811764
TI  - Entomological contributions to genetics: studies on insect germ cells linked
      genes to chromosomes and chromosomes to mendelian inheritance.

PMID- 12811765
TI  - Induction of P450 monooxygenases in the German cockroach, Blattella germanica L.
AB  - The cytochrome P450 monooxygenases are an important metabolic system whose level
      of activity can be influenced by several dietary constituents. We examined the
      effects of six known P450 inducers on the levels of total cytochromes P450,
      cytochrome b(5), and six monooxygenase activities in adult German cockroaches. In
      addition, the levels of CYP6L1 and CYP9E2 mRNA were also investigated.
      Phenobarbital treatment resulted in increases in total cytochromes P450 and
      metabolism of three resorufin analogues, but not CYP6L1 nor CYP9E2 mRNA. There
      was no significant effect of the other five inducers on any of the monooxygenase
      parameters we measured. In comparison with other insects, the German cockroach
      seems unusually refractory to most inducing agents.

PMID- 12811766
TI  - Cloning and expression of gallerimycin, an antifungal peptide expressed in immune
      response of greater wax moth larvae, Galleria mellonella.
AB  - A novel defensin-like peptide was identified in the greater wax moth, Galleria
      mellonella. It was discovered in a haemocyte cDNA bank enriched with transcripts
      upregulated after immune challenge via subtractive hybridisation and suppressive
      PCR. The deduced amino acid sequence of the defensin-like peptide exhibits
      similarities to the antifungal peptides drosomycin from Drosophila melanogaster
      and heliomicin from Heliothis virescens. Therefore, it has been termed
      gallerimycin. Upregulation of gallerimycin after stimulation of the immune system
      by LPS-injection was demonstrated by quantitative real-time PCR. A full-size cDNA
      was cloned and overexpressed in Escherichia coli Origami cells in order to obtain
      a functional peptide with disulfide bridges. The recombinant peptide was active
      against the entomopathogenic fungus Metarhizium anisopliae, but not against
      yeast, gram-negative and gram-positive bacteria.

PMID- 12811767
TI  - Isolation and characterization of a cDNA encoding for a lysozyme from the gut of
      the reduviid bug Triatoma infestans.
AB  - We have isolated and characterised a Triatoma infestans cDNA encoding a lysozyme.
      A 174-bp fragment was amplified by PCR using degenerate oligodeoxyribonucleotide
      primers derived from the known amino acid sequences of lysozyme from other
      insects. This PCR fragment was used to screen a cDNA gut library of T. infestans.
      A clone containing the 3'-end of the lysozyme cDNA (219 bp) was isolated and
      sequenced. RACE was used to amplify the 5'-end of the lysozyme cDNA. After
      sequencing the complete lysozyme cDNA, the deduced 417 amino acid sequence showed
      high identity (40-50%) with other chicken-type lysozymes. The amino acid residues
      responsible for the catalytic activity and the binding of the substrate were
      essentially conserved. The expression pattern of the lysozyme gene in bugs at
      different molting and feeding states showed that this gene was upregulated in the
      digestive tract directly after the molt and after feeding. Additionally, this
      lysozyme gene was expressed differently in the different regions of the digestive
      tract, strongly in the cardia and stomach, the anterior regions of the midgut,
      and only traces of lysozyme mRNA could be detected in the small intestine, the
      posterior region of the midgut.

PMID- 12811768
TI  - Multichannel surface EMG: basic aspects and clinical utility.
AB  - The generation of the surface electromyogram (sEMG) is described with regard to
      the properties of the single muscle fiber action potential as source, the
      physical aspects of volume conduction and recording configuration, and the
      properties and firing pattern of motor units (MUs). The spatial aspect of the
      motor unit action potential (MUP) is emphasized in relation to the results of
      high-density, multichannel sEMG measurements. The endplate zone, depth, size, and
      position of MUs can be estimated. The use of muscle fiber conduction velocity
      measurements in channelopathies and the changes in pathological fatigue are
      described. Using the unique patterns of spatial spread of MUPs over the skin (MU
      fingerprint), MU classification and the determination of firing moments is done
      noninvasively. Clinical applications of high-density sEMG measurements are
      reviewed. Emerging possibilities provided by MUP size and fingerprint
      measurements in neuromuscular disease and motor control are discussed. We
      conclude that multichannel sEMG adds unique, and sometimes indispensable, spatial
      information to our knowledge of the motor unit.

PMID- 12811769
TI  - Sphincter electromyography and multiple system atrophy.
AB  - Electromyographic studies of the sphincter in patients with multiple system
      atrophy have shown increased duration and polyphasia of motor unit potentials.
      These electrophysiological markers have been used to argue for the selective
      degeneration of sacral motor neurons in Onuf's nucleus in patients with multiple
      system atrophy. Studies comparing sphincter electromyographic changes in patients
      with multiple system atrophy and Parkinson's disease have shown significant
      differences between these two patient populations. Despite the controversy
      surrounding this claim, recent studies using quantitative electromyographic
      techniques support the view that reinnervation of the anal sphincter muscles may
      be a useful diagnostic marker for distinguishing multiple system atrophy from
      Parkinson's disease. A critical review of these data is needed to assess the
      validity and reliability of electromyographic changes in multiple system atrophy.

PMID- 12811770
TI  - Ethical review of research involving human subjects: when and why is IRB review
      necessary?
AB  - Requirements for ethical review of research involving human subjects are based on
      widely accepted international standards that are implemented by various national
      regulations and institutional policies. In the United States, most human research
      is reviewed by institutional review boards (IRBs) applying federal standards.
      Researchers may not realize the variety of studies that should be submitted for
      review. Studies involving interventions must be reviewed regardless of whether
      these are standard interventions, nonmedical interventions, or retrospective
      studies. Quality improvement activities require IRB review if the results may be
      published. Research use of information from medical records or of biomedical
      specimens requires review unless no identifiers are recorded. Review must be
      sought at least annually and whenever the research changes. Even human research
      that is technically exempt from Federal regulations usually needs to have that
      exemption certified by someone other than the researcher.

PMID- 12811771
TI  - Ulnar neuropathy in the forearm: A possible complication of diabetes mellitus.
AB  - Ulnar neuropathy in the forearm is an unusual cause of hand weakness and sensory
      loss that is most often attributed to compression of the nerve distally within
      the humero-ulnar arcade (cubital tunnel). An association with diabetes mellitus,
      however, has not been reported. We identified four patients with type I diabetes
      mellitus and clinical findings suggestive of ulnar neuropathy in whom
      electrophysiologic testing revealed partial conduction block or abnormal temporal
      dispersion within the forearm segment of the ulnar nerve. Although evidence for a
      mild underlying polyneuropathy was present in three patients, the ulnar nerve
      abnormalities were disproportionately severe. In all cases, a Martin-Gruber
      anastomosis was excluded. Whether this lesion is due to an increased propensity
      to focal compression of the ulnar nerve within the humero-ulnar arcade or whether
      it represents a localized manifestation of the generalized polyneuropathy remains
      to be determined.

PMID- 12811772
TI  - Time and magnitude of torque generation is impaired in both arms following
      stroke.
AB  - Muscle strength, usually measured as the peak torque during maximal contraction,
      is impaired in persons with stroke. Time-dependent properties of muscle
      contraction may also be altered but have not been quantified. We quantified both
      magnitude (peak torque) and time-dependent parameters (times to develop and
      reduce torque) in eight different isometric joint actions. Parameters were
      compared among the more and less affected arms of 20 persons with chronic stroke
      and the nondominant arms of 10 similarly aged healthy persons. Torque-generation
      parameters were independent from one another (i.e., low correlations) and highly
      reliable between trials and days. All parameters were impaired in the more
      affected arm, whereas peak torque and time to develop torque were impaired in the
      less affected arm. Following stroke, torque-generation impairments include both
      magnitude and time-dependent properties and exist not only in the more affected
      but also in the less affected arm. Clinicians attempting to improve upper
      extremity function should employ therapeutic exercises that challenge patients to
      improve both their strength and speed of muscle contraction.

PMID- 12811773
TI  - Knee extensor torque, work, and EMG during subjectively graded dynamic
      contractions.
AB  - We examined knee extensor peak torque, work, and electromyogram (EMG) during
      dynamic contractions to perceived exertion levels in men and women. Thirty
      subjects performed three maximal effort isokinetic knee extensions (60 deg x s(
      1)), followed by three contractions to each of nine separate levels of perceived
      exertion. Surface EMG of the vastus medialis (VM), vastus lateralis (VL), and
      rectus femoris (RF), and knee extensor peak torque and work were normalized to a
      percent of each respective value obtained during the maximal effort contractions.
      The results demonstrated a significant linear increase in voluntary knee extensor
      peak torque and work across perceived exertion levels. Knee extensor peak torque
      and work were less than 70%, 80%, and 90% maximal voluntary contraction (MVC) at
      perceived exertion levels 7, 8, and 9, respectively. A significant increase in
      VM, VL, and RF muscle EMG was observed across perceived exertion levels 1 through
      9, with EMG increase highest for the VL. The findings demonstrate that dynamic
      contractions guided by perceived exertion are underproduced at relatively high
      perceptual intensities, and that reliance on VL activation occurs across
      submaximal torque levels. The overestimation of knee extensor peak torque and
      work at relatively high perceptual intensities may suggest the presence of a
      subconscious mechanism aiming to reduce high muscle and joint forces.

PMID- 12811774
TI  - Muscle fiber number in the biceps brachii muscle of young and old men.
AB  - We have compared the number of muscle fibers in the biceps brachii muscle (BB) of
      six old men (82.3 +/- 4.3 years) and six young men (21.2 +/- 1.9 years). Muscle
      fiber number was estimated by dividing the maximal area of the BB, determined
      with magnetic resonance imaging, by the mean fiber area of the BB determined in a
      muscle biopsy. The percentage of type II fibers in the BB ( approximately 60%)
      and the type I fiber area were not different between the groups. The BB area (
      26%), type II fiber area (-24%), mean fiber area (-20%), and maximal voluntary
      contraction strength (MVC) of the elbow flexor muscles (-27%) were lower in the
      old than young group. However, the estimated number of muscle fibers was not
      significantly different between the young (253000) and old (234000) men.
      Consequently, the smaller BB area of the old men could be explained primarily by
      a smaller type II fiber size. These findings suggest that old age is not
      associated with a reduced number of muscle fibers in the BB. The relative
      contribution of a reduction in fiber number to age-related muscle atrophy may be
      muscle-dependent.

PMID- 12811775
TI  - Compressive lumbar myelopathy presenting as segmental motor neuron disease.
AB  - Four patients presented with slowly progressive, bilateral, asymmetric weakness
      and muscle atrophy in the lower extremities, accompanied by cramps and
      fasciculations. Sensory symptoms were insignificant. There was no bladder or
      bowel disturbance. Upper extremities and cranial nerves were normal. Weakness was
      found in lumbosacral myotomes, ranging from L2 to S1. The tendon reflexes varied,
      and extensor plantar responses were found in one case with proximal leg
      involvement. Nerve conduction studies were normal, but segmental chronic and
      often active denervation confined to the weak myotomes in the lower extremities
      was found in the electromyogram. Magnetic resonance imaging showed evidence of
      spondylotic lumbosacral myelopathy associated with disc herniation or osteophytic
      arthropathy at the T11/T12 spinal level in all patients, with increased signal
      within the adjacent cord. This unusual purely motor presentation may result from
      ischemic myelopathy secondary to compression of the anterior spinal artery.

PMID- 12811776
TI  - Strength training alters the viscoelastic properties of tendons in elderly
      humans.
AB  - The effect of strength training for 14 weeks on patella tendon viscoelastic
      properties was investigated in a group of elderly individuals. Participants were
      assigned to training (age [mean +/- SD] 73.6 +/- 3.4 years; n = 7) or control
      (age 66.4 +/- 1.7 years; n = 7) groups. Training was performed three times per
      week and consisted of two series of 10 repetitions of leg-extension and leg-press
      exercises at 80% of the 5-repetition maximum. Tendon elongation during an
      isometric knee-extension contraction-relaxation was measured using
      ultrasonography. Tendon stiffness was calculated from the gradient of the
      estimated force-elongation relationship and mechanical hysteresis was calculated
      as the area between loading-unloading curves. Knee-flexor coactivation, estimated
      from biceps femoris muscle electromyographic activity, was unaltered (P > 0.05)
      after the training and control periods. No changes (P > 0.05) were observed in
      stiffness or hysteresis after the control period. In contrast, tendon stiffness
      increased from 1376 +/- 811 to 2256 +/- 1476 N x mm(-1) (P < 0.01) and hysteresis
      decreased from 33 +/- 5 to 24 +/- 4% (P < 0.05), after training. These training
      induced adaptations have implications for maximal muscle force, rate of force
      development, and metabolic cost of locomotion.

PMID- 12811777
TI  - F-wave acquisition using low-current stimulation.
AB  - The purpose of this study was to assess the feasibility of utilizing low-current
      stimulation for F-wave generation, thereby avoiding the discomfort of repetitive
      supramaximal stimulation. We employed the same technique as is used for
      generating F waves in the conventional way, except for using a stimulating
      current that was just strong enough to evoke a motor response on the
      oscilloscope. This usually required a stimulus of about 10-15 mA at 0.2-ms
      duration. Both median nerves of 30 subjects were evaluated with this technique
      and with F waves generated by the conventional technique in the same subjects.
      Amplitudes were larger when using supramaximal current stimulation. However,
      there was no statistical difference between F-wave latencies, chronodispersion,
      and persistence (penetrance) elicited with maximal and low-current stimulation.
      This procedure should represent a significant improvement for patient comfort
      during electrodiagnostic procedures involving F-wave studies.

PMID- 12811778
TI  - Effects of endurance training on satellite cell frequency in skeletal muscle of
      old men.
AB  - We investigated the effects of endurance training on satellite cells, which are a
      major component of the regenerative capacity of muscles. Muscle biopsies were
      obtained from the vastus lateralis of 11 men aged between 70 and 80 years who
      trained for 14 weeks (work load corresponding to 65-95% of peak oxygen
      consumption, VO(2) peak). Satellite cells were identified by
      immunohistochemistry. There was a significant increase in satellite cell number.
      Additionally, VO(2) peak, citrate synthase activity, and the area of type IIA
      fibers were significantly increased. Fiber type distribution and the myonuclear
      number were not significantly affected. The enhancement of satellite cell
      frequency and fiber area indicate that endurance training is an efficient
      strategy to improve muscle function in the elderly.

PMID- 12811779
TI  - Comparison between impairment and disability scales in immune-mediated
      polyneuropathies.
AB  - The ability of a scale to detect clinical relevant changes over time, i.e., its
      "responsiveness," may help clinicians to choose among valid and reliable
      measures. Therefore, we investigated the responsiveness' rank ordering (best to
      worse) of six selected valid and reliable scales, namely the Medical Research
      Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole
      peg, ten-meters walking, and a disability-sumscore, in immune-mediated
      polyneuropathies. Patients with newly diagnosed Guillain-Barre syndrome (n = 7)
      or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over
      52 weeks. Responsiveness of each scale was measured using different methods
      (effect-size, standardized response mean score, Wilcoxon matched-pairs signed
      rank, and a newly devised Schmitz's distribution-free responsiveness score), and
      the obtained scores in each method were plotted against the follow-up period,
      thus allowing area-under-the-curve calculations (higher area-under-the-curve
      indicating better responsiveness). Also, longitudinal correlations were performed
      between the scales' values and patients' own clinical judgments (deteriorated,
      unchanged, improved) (higher correlation = better responsiveness). A consistent
      rank ordering was observed in each technique with the disability-sumscore, MRC
      sumscore, and Vigorimeter being among the best responsive scales. Hence, the
      primary use of these measures is suggested in studies of immune-mediated
      polyneuropathies.

PMID- 12811780
TI  - Quantitative measurement of muscle fiber composition in a normal population.
AB  - To obtain normative muscle morphology data on a healthy population recruited from
      a population survey, we examined vastus lateralis biopsies from 58 men and 33
      women, aged 26-67 years. Biopsies were measured with automated, computer-aided
      techniques. Data were analyzed according to gender and age, and the influence of
      blood pressure, body mass index (BMI), and smoking habits was also examined. Men
      had larger muscle fibers (fiber area approximately 5400 microm(2)) than women (
      approximately 4000 microm(2), P = 0.003). No gender differences were seen in
      fiber composition, fiber roundness, percentage of connective tissue, or capillary
      density. Blood pressure did not influence fiber size or composition, but was
      correlated with fiber roundness in men. BMI was associated with fiber area in
      men, but not in women. Variations in age, smoking habits, and physical activity
      did not influence muscle morphology data substantially. Thus, in a normal
      population, men have larger muscle fibers than women, but similar fiber
      composition. Variation in gender, BMI, blood pressure, and physical activity may
      influence morphological features to a minor degree.

PMID- 12811781
TI  - Hexosaminidase A deficiency is an uncommon cause of a syndrome mimicking
      amyotrophic lateral sclerosis.
AB  - Patients with adult hexosaminidase A (Hex A) deficiency may have clinical
      manifestations similar to amyotrophic lateral sclerosis (ALS). Mutations in the
      hexosaminidase A (HEXA) gene are common in the Jewish Ashkenazi population in
      Israel. Serum samples of 115 Israeli patients with sporadic ALS were screened for
      enzymatic activity to detect "enzyme-based carriers." Fifteen samples with low (<
      50%) enzymatic activity were subjected to mutation analysis, which included the
      two common mutations in the HEXA gene among Ashkenazi Jews (+1278TATC and
      IVS12+1G-->C). Three "enzymatic carrier" patients of Moroccan origin were checked
      for two additional mutations (DeltaF304/305 and Arg170-->Gln), specific to this
      ethnic group. Two "enzymatic carrier" patients of Iraqi origin were analyzed for
      the mutation Gly250-->Val, specific to this population. The mutation Gly 269-
      >Ser was screened in carriers of Ashkenazi origin only (n = 10). The only
      abnormalities found were heterozygous +1278TATC mutations in two Ashkenazi
      patients. Their clinical presentation was not different from that usually
      encountered in ALS. The frequency of mutations in the HEXA gene among Israeli ALS
      patients was not higher than in the healthy Israeli population. Therefore, Hex A
      deficiency seems to be a very unlikely cause of an ALS-mimic syndrome.

PMID- 12811782
TI  - Novel missense mutation and large deletion of GNE gene in autosomal-recessive
      inclusion-body myopathy.
AB  - The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene is
      the causative gene for autosomal-recessive hereditary inclusion-body myopathy (h
      IBM). Two sisters affected with autosomal-recessive h-IBM were shown to be
      compound heterozygous for two novel GNE mutations: a large deletion involving
      exons 1-9, and a R162C amino acid change in the epimerase domain. This is the
      first deletion event observed in a GNE allele and expands the molecular
      pathogenesis of autosomal-recessive h-IBM.

PMID- 12811783
TI  - Adult Hallervorden-Spatz syndrome simulating amyotrophic lateral sclerosis.
AB  - Hallervorden-Spatz syndrome (HSS) is a neurodegenerative disorder characterized
      by progressive dementia, dystonia, ataxia, and rigidity. An atypical form of
      adult-onset HSS was observed in a 36-year-old man presenting with progressive
      dysarthria. Markedly dysarthric speech and a weak atrophic tongue associated with
      a neurogenic pattern of motor unit recruitment in bulbar-supplied muscles on
      electromyography led to an initial impression of bulbar amyotrophic lateral
      sclerosis (ALS). Lack of expected progression of symptoms, however, prompted
      reinvestigation. Repeat brain magnetic resonance imaging demonstrated an "eye-of
      the-tiger" pattern in the basal ganglia, characteristic of HSS, thus requiring
      genetic studies. DNA analyses of the pantothenate kinase gene (PANK2) was
      conducted and revealed two novel, disease-causing exon 3 missense mutations
      (Cys231Ser and Tyr251Cys). This case broadens the genotypic and phenotypic
      spectrum of HSS to include a late-onset syndrome resembling bulbar-onset ALS.

PMID- 12811784
TI  - Masticator myopathy.
AB  - A 31-year-old woman developed low-grade fever and pain and swelling of the
      masticatory muscles. A T2-weighted magnetic resonance image showed high signal
      intensity in these muscles. Coxsackie B3 and echo 30 viruses were detected from a
      nasopharyngeal swab and feces, respectively. The clinical symptoms accompanied a
      marked decline in the serum immunoglobulin G level with progressive eosinophilia.
      Her symptoms disappeared by 8 weeks after onset. She was diagnosed as having
      masticator myopathy, which has rarely been reported in humans. The present case
      suggests that masticator myopathy is associated with coxsackie or echo virus
      infection.

PMID- 12811785
TI  - Chronic sensory ataxic neuropathy with polyclonal IgM reactivity to various
      disialosyl gangliosides.

PMID- 12811787
TI  - Sonographic detection of multifocality in breast carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic accuracy and
      clinical value of preoperative sonographic detection of multifocality in breast
      carcinoma. METHODS: Between November 1, 1999, and November 30, 2000, we
      prospectively compared the sonographic and histopathologic findings for all
      nodules measuring 1 cm or less in the longest dimension on sonography in 19
      consecutive patients diagnosed with breast carcinoma. For each nodule, the final
      histopathologic diagnosis, size, and, in cases of nodules in the same breast as
      the primary lesion, the distance from that lesion were evaluated. RESULTS: The 19
      patients examined, all of whom were women, had a mean age of 42.1 years (range,
      28-62 years). Thirty nodules were detected on sonography: 15 patients had a total
      of 24 nodules in the ipsilateral breast, 2 patients each had 1 nodule in the
      contralateral breast, and 2 patients each had 1 nodule in the ipsilateral breast
      and 1 nodule in the contralateral breast, for a total of 26 ipsilateral and 4
      contralateral nodules. Of the 30 lesions, 20 (67%) appeared to be malignant (ie,
      satellite nodules) on sonography. Histopathologic examination showed that of
      these malignant-looking lesions, 15 (75%), which were found in 10 patients, were
      malignant and 5 (25%), which were found in 4 patients, were benign. For 7 (70%)
      of the 10 patients whose nodules appeared malignant on sonography, the initial
      treatment plan was changed because of the sonographic findings. Ten lesions were
      assessed as benign on sonography; histopathologic examination confirmed that all
      10 were benign. Sonography had a sensitivity of 100%, a specificity of 67%, a
      positive predictive value of 75%, a negative predictive value of 100%, and an
      accuracy rate of 83%. The mean size of the nodules was 0.8 cm (range, 0.3-1.4
      cm). The mean distance of the 26 ipsilateral nodules from the primary lesion was
      1.8 cm (range, 0.5-6 cm). CONCLUSIONS: Preoperative sonography is accurate and
      reliable for detecting small satellite nodules and can have an important role in
      the preoperative evaluation of patients for whom breast-conserving surgery is
      planned.

PMID- 12811788
TI  - Eyelid movements in normal human fetuses.
AB  - PURPOSE: We undertook this study to investigate the characteristics of blinking
      activity in healthy human fetuses. METHODS: Blinking activity was studied
      sonographically in healthy fetuses between 33 and 42 weeks' menstrual age.
      Horizontal and coronal sonographic views of the eye were obtained and videotaped.
      Fetal blinking movements were analyzed by reviewing the videotape in slow motion.
      Fetal vibroacoustic stimulation was also used when clinically indicated. RESULTS:
      We examined a total of 18 healthy fetuses. Fetal blinking was detected in 89% of
      cases, with a mean frequency of 6.2 movements per 60-minute observation period.
      Vibroacoustic stimulation was associated with increased fetal blinking in the 6
      fetuses in which it was applied (mean, 15.3 movements per 60-minute observation
      period). CONCLUSIONS: Blinking is a normal fetal activity. The increased
      frequency of blinking activity associated with vibroacoustic stimulation may be
      considered a part of the normal startle reflex.

PMID- 12811789
TI  - Quantitative assessment of fetal bowel echogenicity: comparison of harmonic,
      compound, and fundamental sonographic images.
AB  - PURPOSE: The aims of this study were to assess normal fetal bowel echogenicity
      quantitatively and to compare the levels of bowel echogenicity observed with the
      use of 3 different sonographic image-processing techniques-harmonic plus compound
      imaging, harmonic imaging alone, and fundamental imaging-and 2 different
      broadband transducers. METHODS: Women with normal singleton second-trimester
      fetuses underwent sonographic scanning with both a 2-5-MHz and a 4-7-MHz
      transducer. The use of the 3 imaging techniques and the 2 transducers resulted in
      6 types of images: 2-5-HC (harmonic plus compound images), 2-5-H (harmonic
      images), and 2-5-F (fundamental images), and 4-7-HC, 4-7-H, and 4-7-F images. The
      relative echogenicities (brightness) of the fetal bowel and iliac bone were
      measured, and bowel echogenicity ratios (bowel echogenicity/iliac bone
      echogenicity x 100) were calculated using graphics software. The resulting data
      were analyzed to evaluate differences in echogenicity ratios between the 6 types
      of images. RESULTS: We examined 37 fetuses during the study period. The bowel
      echogenicity ratios were highest on the images obtained with harmonic and
      compound-imaging techniques (2-5-HC, 84.7 +/- 23.4%; 4-7-HC, 98.5 +/- 36.4%). The
      bowel echogenicity ratio for the 2-5-HC images was significantly higher than
      those for the 2-5-H and the 2-5-F images (p < 0.01 and p < 0.001, respectively),
      and those for the 4-7-HC and 4-7-H images were higher than that for the 4-7-F
      images (p < 0.01 for both comparisons). CONCLUSIONS: A sonographic finding of
      echogenic fetal bowel should be interpreted cautiously because the use of special
      image-processing techniques can artificially enhance the apparent level of
      echogenicity of the bowel. We recommend rescanning without the use of those
      techniques if the fetal bowel appears to have an increased level of echogenicity.

PMID- 12811790
TI  - Color Doppler sonography of orbital and vertebral arteries in migraineurs without
      aura.
AB  - PURPOSE: The objective of this study was to investigate whether the retrobulbar
      hemodynamics in the ophthalmic (OA), posterior ciliary (PCA), central retinal
      (CRA), and vertebral (VA) arteries are affected in migraineurs without aura.
      METHODS: The eyes of migraineurs without aura and those of healthy control
      subjects were evaluated during both headache and headache-free periods.
      Retrobulbar and vertebral blood flow velocities in the OA, PCA, CRA, and the
      extracranial part of the VA were measured bilaterally using color Doppler
      sonography. The peak systolic and end-diastolic flow velocities and the
      pulsatility (PI) and resistance (RI) indices were determined for all arteries.
      RESULTS: In total, we enrolled 30 migraineurs and 31 healthy control subjects.
      Statistically significant differences between headache-free migraineurs and
      control subjects were observed in the PI and RI of both right and left PCAs and
      in the RI of both right and left CRAs. The PI and RI of the left VA of the
      migraineurs were significantly lower during both headache and headache-free
      periods than were those of the control subjects. Among the migraineurs, the peak
      systolic and end-diastolic velocities of the left VA were increased during
      headache periods relative to those found during the headache-free periods.
      CONCLUSIONS: The retrobulbar circulation and flow hemodynamics in the left VA may
      be altered in both headache and headache-free periods in migraineurs without
      aura. The differences found between migraineurs and control subjects may
      implicate autonomic dysfunction in migraineurs.

PMID- 12811791
TI  - Sonographic measurement of kidney size in geriatric patients.
AB  - PURPOSE: The aim of this study was to compare the value of absolute and relative
      renal length (ARL and RRL, respectively) measurements in determining variations
      in normal kidney size related to sex, body height, and increasing age among
      patients older than 60 years. METHODS: Kidney sizes were prospectively measured
      sonographically in patients older than age 60 years. Longitudinal renal lengths
      (ARLs) were measured, and the RRLs were calculated by dividing the ARL by the
      body height. ARL and RRL measurements were analyzed according to sex, age, and
      body height. RESULTS: The ARLs and RRLs of the left kidney in 236 patients were
      significantly greater than those of the right kidney (p < 0.05) in both sexes.
      The ARLs for both kidneys were also significantly greater in men than they were
      in women (p < 0.05). In contrast, the RRLs for both kidneys were significantly
      lower in men than they were in women (p < 0.05). Both left and right ARLs
      decreased significantly with increasing age regardless of sex (p < 0.01 and p <
      0.05, respectively). The same was true for left and right RRLs (p < 0.01 and p <
      0.05, respectively). CONCLUSIONS: Renal size decreases with increasing age among
      patients older than 60 years. In our series of geriatric patients, the use of
      RRLs could not completely eliminate variations related to a subject's height,
      sex, and age. Therefore, we recommend that the ARL be used for renal measurements
      in geriatric patients.

PMID- 12811792
TI  - Visualization of bilateral carotid cavernous sinus fistulas with duplex
      sonography.
AB  - Duplex sonography used as a primary diagnostic tool in the case of a 17-year-old
      boy with a traumatic head injury revealed bilateral carotid cavernous sinus
      fistulas, with bilateral dilated venous convolutions next to the carotid siphon
      and dilated superior ophthalmic veins. A bilateral craniectomy allowed
      visualization of the entire circle of Willis together with the dilated cavernous
      sinuses. Doppler spectral analysis of blood flow in the arterialized superior
      ophthalmic veins revealed an arterialized venous pattern with retrograde and
      increased blood flow. The same blood flow profile was found in the venous
      cavernous sinuses. These findings were confirmed by digital subtraction
      angiography. We planned to perform embolization of the patient's fistulas, but
      intracranial and subarachnoid hemorrhaging developed, and the patient died the
      day before the procedure was to have been performed. The entire pathologic state
      of carotid cavernous sinus fistulas, from their origin beside the carotid siphon
      to the superior ophthalmic veins, can be visualized with duplex sonography,
      particularly when patients have undergone craniectomy. We believe that patients
      with frontal or basilar skull fracture should undergo duplex sonographic
      examination to detect carotid cavernous sinus fistulas.

PMID- 12811793
TI  - Acute increase in intracranial pressure revealed by transcranial Doppler
      sonography.
AB  - Increased pulsatility of blood flow in the basal cerebral arteries recorded with
      the use of transcranial Doppler sonography (TCD) corresponds to increased
      intracranial pressure (ICP) to near the level of the diastolic arterial blood
      pressure. We describe the case of a 39-year-old woman who developed acute
      reduction in consciousness, anisocoria, gaze deviation, and right-sided
      hemiparesis 2 days after resection of a relapsed astrocytoma. MRI revealed only a
      moderate enlargement of the ventricles, but TCD revealed highly pulsatile
      waveforms of all basal cerebral arteries, showing a biphasic pattern with
      diastolic backflow. This pattern was interpreted as a massive increase in ICP
      with imminent danger of cerebral circulatory arrest corresponding to acute
      malresorptive hydrocephalus. External cerebrospinal fluid drainage was
      immediately undertaken, revealing excessive ICP of more than 50 cm H(2)O. Twenty
      four hours after this intervention, both the ICP and the Doppler waveforms had
      returned to normal. This case illustrates the usefulness of TCD for diagnosing a
      critical but potentially reversible acute increase in ICP with imminent cerebral
      circulatory arrest.

PMID- 12811794
TI  - Enlarged fetal bladder: Differential diagnosis and outcomes.
AB  - The sonographic finding of an enlarged fetal bladder may simply be a transitory
      normal variant, but it may also be secondary to reflux or to obstructive,
      neurogenic, or myopathic causes. In this report, we describe the cases of 3
      fetuses with an enlarged bladder, each of which had a different cause. The first
      fetus had posterior urethral valve obstruction, the second, a ruptured neurogenic
      bladder, and the third, megacystic-microcolon-intestinal hypoperistalsis
      syndrome. When sonographic examination reveals an enlarged fetal bladder, the
      ureter, kidneys, genitalia, and spine should be evaluated carefully. Although
      sonography is good at identifying urinary tract abnormalities, it often cannot
      provide the specific diagnosis or cause. We recommend frequent sonographic
      monitoring to evaluate such fetuses for persistence of or changes in bladder
      enlargement and for changes in the volume of amniotic fluid because these signs
      may be indicators of abnormalities of renal function and risk factors for a poor
      prognosis. Analysis of fetal electrolyte levels can also aid in determining the
      prognosis and whether the condition is amenable to therapeutic intervention.

PMID- 12811795
TI  - Nonsurgical diagnosis and management of an inflammatory pseudotumor of the spleen
      in a child.
AB  - Primary splenic tumors in children are rare and usually benign. We report the
      case of a 7-year-old boy with a splenic mass that initially resembled an
      infectious process. Histopathologic examination of a specimen obtained using
      sonographically guided Tru-cut needle biopsy, performed after angiography,
      revealed an inflammatory pseudotumor of the spleen, an extremely rare benign
      lesion. The lesion has been managed conservatively with clinical and sonographic
      follow-up. This case shows that benign lesions of the spleen can easily be
      diagnosed using current radiologic and histopathologic techniques without the
      need for surgery, thus allowing total or even partial splenectomy to be reserved
      for patients in whom a mass cannot be diagnosed or in whom clinical progression
      is evident.

PMID- 12811798
TI  - Specific roles of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide
      induced fever and Fos expression in rat brain.
AB  - Fever is a coordinated autonomic, endocrine, and behavioral response mediated by
      the brain in reaction to inflammatory stimuli. An essential step in transmitting
      the immune signal to the brain is the formation of prostaglandin E2.
      Cyclooxygenase (COX) is the critical enzyme in the synthesis of prostaglandins
      and COX-2, the inducible form of the enzyme, is markedly induced in cells
      associated with the cerebral blood vessels and the leptomeninges by immune
      stimuli such as intravenous administration of lipopolysaccharide (LPS). However,
      the specific roles of COX-1, the constitutive form of cyclooxygenase, and COX-2
      in LPS-induced fever are not well understood. We injected LPS i.v. in combination
      with either a highly selective COX-1 (SC-560) or COX-2 (SC-236) inhibitor to
      determine the effects of each drug on the subsequent fever response and on the
      pattern of expression of Fos protein in the brain. The COX-2 inhibitor blocked
      LPS-induced fever and Fos expression in sites such as the ventromedial preoptic
      nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos
      immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral
      medulla (VLM), and parabrachial nucleus (PB) remained. In contrast, the COX-1
      inhibitor resulted in a profound hypothermic response to LPS and blocked LPS
      induced Fos-immunoreactivity in the PVH, PB, NTS, and VLM, although it had no
      effect on the VMPO. Although COX-2 plays a dominant role in mediating fever
      responses to i.v. LPS, at least some components of the response, including
      avoiding hypothermia and the induction of Fos in the NTS, VLM, PB, and PVH,
      appear to depend on COX-1. J.

PMID- 12811799
TI  - Synaptic organization of tooth pulp afferent terminals in the rat trigeminal
      sensory nuclei.
AB  - Previous studies provide evidence that a structure/function correlation exists in
      the distinct zones of the trigeminal sensory nuclei. To evaluate this
      relationship, we examined the ultrastructure of afferent terminals from the tooth
      pulp in the rat trigeminal sensory nuclei: the principalis (Vp), the dorsomedial
      part of oral nucleus (Vdm), and the superficial layers of caudalis (Vc), by using
      transganglionic transport of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP). A total of 93 labeled boutons were serially sectioned, in
      which some sections were incubated with gamma-aminobutyric acid (GABA) antiserum.
      Almost all labeled boutons formed asymmetric contact with nonprimary dendrites,
      in which more than half of labeled boutons in the Vc made synapses with their
      spines. The labeled boutons could be divided into two types on the basis of
      numbers of dense-cored vesicles (DCVs) in a boutons: S-type and DCV-type. Almost
      all labeled boutons in the Vp and Vdm were S-type, whereas two types were
      distributed evenly in the Vc. In contrast to DCV-type boutons, the S-type was
      frequently postsynaptic to unlabeled axon terminals containing a mixture of
      round, oval, and flattened vesicles (p-endings) and forming symmetrical synapses.
      Most p-endings examined were immunoreactive to GABA. The frequency of axoaxonic
      contacts was higher for labeled boutons in the Vp than in the Vdm and Vc. These
      results suggest that the three structures of trigeminal sensory nuclei serve
      distinct functions in nociceptive processing.

PMID- 12811800
TI  - Differential distribution of butyrylcholinesterase and acetylcholinesterase in
      the human thalamus.
AB  - It has been hypothesized that acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE) are coregulators of the duration of action of
      acetylcholine in cholinergic neurotransmission, suggesting that BuChE may also
      have an important role in the brain. To compare the expression of cholinesterases
      in the human thalamus, the distributions of BuChE and AChE activity were studied
      by using a modified Karnovsky-Roots method. BuChE activity was present mainly in
      neurons, whereas AChE activity was present in both neurons and axons. There was
      intense staining for BuChE or AChE throughout the thalamus, with some nuclei
      primarily expressing one or the other cholinesterase. BuChE staining was most
      intense and widespread in neurons in the anteroventral, mediodorsal, ventral,
      lateral, and pulvinar thalamic nuclei. AChE was predominantly expressed in
      neurons of the anterodorsal, midline, ventral, intralaminar, and reticular
      nuclei. Many nuclei contained both cholinesterases. Considering the overall
      patterns of labeling in the thalamus for the two cholinesterases, there were both
      complementary and overlapping relationships of BuChE and AChE activity. Neuronal
      staining in the subthalamic nucleus and hypothalamus was predominantly positive
      for AChE activity. The distinct distribution of BuChE activity in neurons in the
      human thalamus is consistent with an important role for this enzyme in
      neurotransmission in the human nervous system. Furthermore, BuChE activity, like
      AChE activity, is found in certain thalamic nuclei related to cognitive and
      behavioral functions. Involvement of thalamic nuclei in diseases of the nervous
      system such as Alzheimer's disease and schizophrenia suggests that BuChE could be
      a potential target for therapeutic intervention in these disorders.

PMID- 12811802
TI  - Two epochs in the development of gamma-aminobutyric acidergic neurons in the
      ferret thalamus.
AB  - These studies chart the development of gamma-aminobutyric acid (GABA)-ergic
      neurons in the three divisions of the thalamus (ventral thalamus, dorsal
      thalamus, and epithalamus). GABAergic neurons were identified by in situ
      hybridization to localize mRNA for 67-kDa glutamic acid decarboxylase (GAD(67))
      and related to the morphological maturation of the thalamus in fetal and
      postnatal brains and to expression of transcription factors Gbx-2 and Tbr-1.
      Origins of GABAergic neurons were sought in in vitro slice preparations incubated
      in bromodeoxyuridine or injected with a carbocyanine dye. GABA neurons of ventral
      thalamus (reticular nucleus, ventral lateral geniculate nucleus, zona incerta,
      and nucleus of the fields of Forel) and of epithalamus appear at least 14 days
      before those intrinsic to dorsal thalamus. Ventral thalamus GABA cells are
      derived from a region connecting the ventricular zone of the third ventricle to
      the caudal ganglionic eminence. This region is delimited ventrally by the Tbr-1
      expressing prethalamic eminence and dorsally by the Gbx-2-expressing part of the
      dorsal thalamus. GABA neurons of epithalamus are derived from the embryonic
      pretectum. Neurons continue to be added to the ventral thalamus, perireticular
      nucleus, entopeduncular nucleus, and substantia nigra from the ganglionic
      eminence as development proceeds. GAD(67)-expressing cells of dorsal thalamus
      become detectable only at birth and populate the thalamus from posterior to
      anterior over the first week of life. Although a very small number reaches the
      dorsal lateral geniculate nucleus from the caudal ganglionic eminence, there is
      no obvious new source of proliferating neurons at this stage. Intrinsic GABA
      cells of dorsal thalamus may, therefore, derive from an early generated
      population of cells that turns on a GABAergic phenotype only late in development.

PMID- 12811804
TI  - Perirhinal and parahippocampal cortices of the macaque monkey: cytoarchitectonic
      and chemoarchitectonic organization.
AB  - Findings from recent tract-tracing studies examining the cortical and subcortical
      connectivity of the medial temporal lobe showed that the pattern of connections
      of areas TH and TF of the parahippocampal cortex were consistent with previous
      boundary demarcations of this region. In contrast, the connections of the
      perirhinal cortex (areas 35 and 36) indicated that the border of area 36 should
      be placed several millimeters more lateral than in earlier descriptions in the
      literature. The connections of this region also suggested that the perirhinal
      cortex extends rostrodorsally to include the medial portion of what is typically
      referred to as the temporal pole (areas TG, 38, or Pro). To determine if cyto-
      and chemoarchitectonic characteristics are consistent with the boundary scheme
      suggested by our tract-tracing studies, we carried out a detailed analysis of
      Nissl- and SMI-32-stained material throughout the perirhinal and parahippocampal
      cortices of the macaque monkey. The staining patterns seen in both these
      preparations are in excellent agreement with the boundaries defined by earlier
      connectional studies. Based on these studies, we recognize areas 35 and area 36
      of the perirhinal cortex and area 36 contains five subdivisions. The
      parahippocampal cortex is composed of areas TH and TF and area TF contains two
      subdivisions. For both the perirhinal and parahippocampal cortices, we provide
      descriptions of the cytoarchitectonic and chemoarchitectonic features that are
      most useful for defining each cortical subdivision, as well as the features most
      useful for defining the boundaries with adjacent cortical regions. We discuss
      these findings in the context of the results of previous tract-tracing studies.

PMID- 12811805
TI  - Reelin-immunoreactive neurons, axons, and neuropil in the adult ferret brain:
      evidence for axonal secretion of reelin in long axonal pathways.
AB  - Reelin is a large secretable protein which, when developmentally defective,
      causes the reeler brain malformation in mice and a recessive form of
      lissencephaly with cerebellar hypoplasia in humans. In addition, Reelin is
      heavily expressed throughout the adult brain, although its function/s there are
      still poorly understood. To gain insight into which adult neuronal circuits may
      be under the influence of Reelin, we systematically mapped Reelin-immunoreactive
      neuronal somata, axons, and neuropil in the brain and brainstem of ferrets.
      Results show that Reelin immunoreactivity is found in widespread but specific
      sets of neuronal bodies, axonal tracts, and gray matter neuropil regions.
      Depending on the region, the immunoreactive neuronal somata correspond to
      interneurons, projection neurons, or both. Some well-defined axonal projection
      systems are immunoreactive, whereas most other white matter tracts are unlabeled.
      The labeled pathways include, among others, the lateral olfactory tract, the
      entorhinohippocampal (perforant) pathway, the retroflex bundle, and the stria
      terminalis. Labeled axons in these tracts contain large numbers of discrete, very
      small, immunoreactive particles, suggestive of secretory vesicles under the light
      microscope. The neuropil in the terminal arborization fields of these axons is
      also heavily immunoreactive. Taken together, our observations are consistent with
      the notion that some neurons may anterogradely transport Reelin along their axons
      in large membrane-bound secretory vesicles (Derer et al. [2001] J. Comp. Neurol.
      440:136-143) and secrete it into their terminal arborization fields, which may be
      quite distant from the somata synthesizing the protein. These findings have
      implications for identifying where Reelin acts in adult brain circuits.

PMID- 12811806
TI  - Identification of spinal neurons involved in the urethrogenital reflex in the
      female rat.
AB  - The urethrogenital (UG) reflex is a spinal sexual reflex that consists of
      autonomic and somatic nerve activity and vaginal, uterine, and anal sphincter
      contractions. The UG reflex is under tonic descending inhibition by neurons in
      the region of the nucleus paragigantocellularis (nPGi). The location of spinal
      neurons activated by the UG reflex was examined in the female rat using the
      immediate early gene, c-fos. In addition, the descending inputs from the nPGi
      onto fos-activated neurons was examined using the anterograde tracer biotin
      dextran amine injected into the nPGi. The UG reflex resulted in a significant
      increase in fos-positive nuclei in segments T12-S1, compared with experimental
      controls in which the UG reflex was not activated. Spinal circuits involved in
      the UG reflex include neurons relaying afferent information from the pudendal
      sensory nerve, in the dorsal horn and medial cord of L5-S1. Efferent output
      includes preganglionic neurons located in the lateral gray of L5-S1 and lateral
      and medial gray of T13-L2. Spinal interneurons involved in the UG reflex were
      found close to the preganglionic neurons and in the dorsal horn and intermediate
      and medial gray of T12-S1. NPGi inputs were found primarily on the autonomic
      efferents and interneurons in the medial and intermediate gray. These studies
      demonstrate multisegmental spinal circuits activated with the UG reflex and
      demonstrate that the descending inhibition from the nPGi is by means of
      preganglionic and somatic efferents and spinal interneurons closely associated
      with the efferent output.

PMID- 12811807
TI  - Cholinergic neuropathology in a mouse model of Alzheimer's disease.
AB  - Transgenic mice overexpressing mutant human amyloid precursor protein (PDAPP
      mice) develop several Alzheimer's disease (AD)-like lesions including an age
      related accumulation of amyloid-beta (Abeta)-containing neuritic plaques.
      Although aged, heterozygous PDAPP mice also exhibit synaptic and glial cell
      changes characteristic of AD pathology, no evidence of widespread neuronal loss
      has been observed. The present study sought to determine whether homozygous PDAPP
      mice, which express very high levels of Abeta peptide, exhibit AD-like
      cholinergic degenerative changes, and whether the changes parallel the deposition
      of Abeta plaques. Mice were examined at 2 and 4 months and at 1 and 2 years of
      age. There was an age-related increase in the density of Abeta plaques in the
      cortex and hippocampus of the PDAPP animals; at 4 months of age there were very
      few plaques, and at 2 years there was a very high density of plaques. There was
      an age-related reduction in the density of cholinergic nerve terminals in the
      cerebral cortex; at 2 months there was a normal density of nerve terminals, but
      as early as age 4 months there was an approximately 50% reduction. However, at
      age 2 years there was no difference in the number or size of basal forebrain
      cholinergic somata compared with 2-month-old PDAPP mice. These data indicated
      that the homozygous PDAPP mouse exhibits cholinergic nerve terminal degenerative
      pathology and that the cortical neurodegenerative changes occur before the
      deposition of Abeta-containing neuritic plaques.

PMID- 12811808
TI  - Cortical connections of the second somatosensory area and the parietal ventral
      area in macaque monkeys.
AB  - To gain insight into how cortical fields process somatic inputs and ultimately
      contribute to complex abilities such as tactile object perception, we examined
      the pattern of connections of two areas in the lateral sulcus of macaque monkeys:
      the second somatosensory area (S2), and the parietal ventral area (PV).
      Neuroanatomical tracers were injected into electrophysiologically and/or
      architectonically defined locations, and labeled cell bodies were identified in
      cortex ipsilateral and contralateral to the injection site. Transported tracer
      was related to architectonically defined boundaries so that the full complement
      of connections of S2 and PV could be appreciated. Our results indicate that S2 is
      densely interconnected with the primary somatosensory area (3b), PV, and area 7b
      of the ipsilateral hemisphere, and with S2, 7b, and 3b in the opposite
      hemisphere. PV is interconnected with areas 3b and 7b, with the parietal
      rostroventral area, premotor cortex, posterior parietal cortex, and with the
      medial auditory belt areas. Contralateral connections were restricted to PV in
      the opposite hemisphere. These data indicate that S2 and PV have unique and
      overlapping patterns of connections, and that they comprise part of a network
      that processes both cutaneous and proprioceptive inputs necessary for tactile
      discrimination and recognition. Although more data are needed, these patterns of
      interconnections of cortical fields and thalamic nuclei suggest that the
      somatosensory system may not be segregated into two separate streams of
      information processing, as has been hypothesized for the visual system. Rather,
      some fields may be involved in a variety of functions that require motor and
      sensory integration.

PMID- 12811809
TI  - Dopamine and histamine in the developing stomatogastric system of the lobster
      Homarus americanus.
AB  - Dopamine and histamine are neuromodulators found in the adult stomatogastric
      nervous system (STNS) of several crustacean species. We used antibodies against
      tyrosine hydroxylase (TH) and histamine to map the distribution and developmental
      acquisition of the dopamine and histamine neurons in the STNS of the lobster,
      Homarus americanus. Embryos, larvae, juvenile and adult animals were studied. TH
      labeling was present in the STNS as early as E80-85 (80-85% of embryonic
      development). A subset of preparations in embryos, larvae, juveniles, and adults
      contained 1-5 labeled somata in the stomatogastric ganglion. Histamine staining
      appeared in the STNS as early as E50. The distribution of both TH and histamine
      staining remained relatively constant through development. Electrophysiological
      recordings demonstrated that receptors for both amines are present in the embryo.
      Bath application of dopamine increased the frequency of the pyloric rhythm in
      embryos, and evidence for dopaminergic activation of peripherally initiated
      spiking in motor axons was seen. In embryos and adults, histamine inhibited the
      motor patterns produced by the stomatogastric ganglion (STG). These data suggest
      that the dopaminergic and histaminergic systems in H. americanus appear
      relatively early in development and that the effects of each are largely
      maintained through development.

PMID- 12811810
TI  - Organization and neural connections of the anterior optic tubercle in the brain
      of the locust, Schistocerca gregaria.
AB  - The anterior optic tubercle is a small neuropil in the insect brain and a major
      target of visual interneurons from the optic lobe. The functional role of the
      tubercle is poorly understood, but recent evidence from locusts points to a
      possible involvement in polarization vision. The present study examines the
      organization of the anterior optic tubercle in the locust Schistocerca gregaria
      and its connections with other brain areas. The tubercle of the locust consists
      of an upper and a lower subunit. Both units are connected in parallel with the
      medulla and lobula of the optic lobe, with the contralateral tubercle, and with
      the lateral accessory lobe in the median protocerebrum. Wide-field transmedullary
      neurons provide input from the medulla. Neurons with processes in the dorsal rim
      of the medulla, a relay station in the polarization vision pathway, project
      exclusively to the lower unit of the tubercle. Visual input from the lobula to
      the upper and lower unit originates from topographically distinct strata. The
      most prominent output target of the tubercle is the lateral accessory lobe in the
      median protocerebrum. Neurons from the upper unit project widely in the lateral
      accessory lobe, whereas neurons from the lower unit have focused projections
      confined to the median olive and to the lateral triangle. The two subunits of the
      anterior optic tubercle are, therefore, processing stages in two parallel visual
      pathways from the optic lobe to the median protocerebrum. Pathways via the lower
      unit of the tubercle appear to be involved in polarization vision.

PMID- 12811811
TI  - Ascending sensory, but not other long-tract axons, regenerate into the connective
      tissue matrix that forms at the site of a spinal cord injury in mice.
AB  - Mice exhibit a unique wound healing response following spinal cord injury in
      which the lesion site fills in with a connective tissue matrix. Previous studies
      have revealed that axons grow into this matrix, but the source of the axons
      remained unknown. The present study assesses whether any of these axons were the
      result of long tract regeneration. C57Bl/6 mice received crush injuries and were
      allowed to survive for 6 weeks to 7 months. Biotinylated dextran amine (BDA) was
      injected into the somato-motor cortex to trace descending corticospinal tract
      (CST) axons, into the midbrain to label descending brainstem pathways including
      the rubrospinal and reticulospinal tracts, or into the L5 dorsal root ganglion to
      trace ascending projections of first-order sensory neurons. Spinal cords from
      other mice were prepared for immunocytochemistry using antibodies against
      neurofilament protein (NF), 5-HT to reveal descending serotonergic axons,
      calcitonin gene-related protein (CGRP) to reveal ascending sensory axons, and
      chondroitin sulfate proteoglycan (CSPG) to assess the distribution of molecules
      that are inhibitory to axon growth. NF immunostaining revealed axons in the
      connective tissue matrix at the lesion site, confirming previous studies that
      used protargol staining. CST axons did not enter the connective tissue matrix,
      but did sprout extensively in segments adjacent to the injury site. Rubrospinal
      and reticulospinal tract axons also did not grow into the lesion site. 5-HT
      positive axons extended to the edge of the lesion, and a few axons followed
      astrocyte processes into the margins of the lesion site. In contrast to the other
      pathways, BDA-labeled ascending sensory axons did extend into and arborized
      extensively within the connective tissue matrix, although the subgroup of
      ascending axons that are positive for CGRP did not. These results indicate that
      the connective tissue matrix is permissive for regeneration of some classes of
      ascending sensory axons but not for other axonal systems.

PMID- 12811812
TI  - Systemic immune challenge induces preproenkephalin gene transcription in distinct
      autonomic structures of the rat brain.
AB  - The involvement of enkephalins in the immune response was investigated in rats
      injected intravenously with interleukin-1beta (2 microg/kg). In situ
      hybridization with a riboprobe complementary to intron A of the preproenkephalin
      (ppENK) gene showed distinct transcriptional activation within several brain
      regions known to be activated by immune stimuli, including the nucleus of the
      solitary tract, the area postrema, the paraventricular hypothalamic nucleus, and
      the oval nucleus of the bed nucleus of the stria terminalis, and dual labeling
      confirmed that a large proportion of the intron expressing neurons co-expressed c
      fos mRNA. Rats injected with saline (controls) showed little or no heteronuclear
      transcript in these structures. The induced signal was strongest after 1 hour but
      was present in some structures 30 minutes after interleukin-1beta injection. At 3
      hours, transcriptional activity returned to basal levels. High basal expression
      of the heteronuclear transcript that appeared unchanged by the immune stimulus
      was seen in regions not primarily involved in the immune response, such as the
      striatum, the olfactory tubercle, and the islands of Calleja and in the immune
      activated central nucleus of the amygdala. The heteronuclear transcript
      colocalized with ppENK mRNA, demonstrating that it occurred in enkephalinergic
      neurons and was not the result of alternative transcription from the ppENK gene
      in other cells. These results demonstrated that enkephalin transcription is
      induced in central autonomic neurons during immune challenge, suggesting that
      enkephalins are involved in the centrally orchestrated response to such stimuli.

PMID- 12811813
TI  - Epstein-Barr virus: induction and control of cell transformation.
AB  - Epstein-Barr virus (EBV), a ubiquitous human herpes virus, is associated with an
      increasing number of lymphoid and epithelial malignancies. The ability of the
      virus to establish life-long persistent infections and induce growth
      transformation is related to the function of a set of viral proteins that are
      variously expressed in both normal and malignant cells. Recent evidence indicates
      that these viral proteins are able to usurp cellular pathways that promote the
      cell growth and survival, while impairing anti-viral immune responses.
      Elucidation of the mechanisms by which EBV induces cell transformation and
      escapes host immune control provides the rational background for the design of
      new strategies of intervention for EBV-related malignancies.

PMID- 12811814
TI  - cDNA array technology in melanoma: an overview.
AB  - Genetic aberrations, mostly resulting in changes in gene expression, are critical
      events in cancer onset and progression. The advent of the cDNA array technology
      allows the screening and the efficient measurement of expression of thousands
      genes simultaneously in a wide spectrum of experimental and clinical models. This
      genomic scale approach is being currently used to obtain global views of human
      cancer gene expression and to identify genetic markers that might be important
      for diagnosis, prognosis, and therapy. This review discusses some recent findings
      obtained by means of cDNA arrays investigating the human melanoma.

PMID- 12811815
TI  - Role of cell-cycle regulatory proteins in gynecological cancer.
AB  - Human malignant tumors are characterized by abnormal proliferation resulting from
      alterations in cell-cycle regulatory mechanisms. This review summarizes the
      current knowledge about these aberrations in malignant tumors of the ovary,
      endometrium, cervix uteri, and vulva. The data indicate that analysis of single
      cell cycle stimulating or inhibiting proteins partly produces unexpected,
      apparently paradoxical results, and cell-cycle regulatory pathways should be
      regarded as a whole in order to identify the molecular mechanisms leading to
      abnormal tumor cell proliferation. For the papillomavirus (HPV)- associated
      cervical and vulvar carcinomas, the manifold effects of the viral oncogenes E6
      and E7 on cell-cycle control are described.

PMID- 12811816
TI  - Participation of bone marrow derived cells in cutaneous wound healing.
AB  - Bone marrow has long been known to be a source of stem cells capable of
      regeneration of the hematopoeitic system. Recent reports, however, have indicated
      that bone marrow might also contain early stem cells that can differentiate into
      other organ tissues such as skin. While these studies have illustrated that bone
      marrow stem cells could find their way to the skin, they have not addressed the
      dynamics of how bone marrow stem cells might participate in the homeostatis and
      regeneration of skin. In this report we followed green fluorescent protein (GFP)
      labeled bone marrow transplanted into non-GFP mice in order to determine the
      participation of bone marrow stem cells in cutaneous wounds. Our results indicate
      that there are a significant number of bone marrow cells that traffic through
      both wounded and non-wounded skin. Wounding stimulated the engraftment of bone
      marrow cells to the skin and induced bone marrow derived cells to incorporate
      into and differentiate into non-hematopoietic skin structures. This report thus
      illustrates that bone marrow might be a valuable source of stem cells for the
      skin and possibly other organs. Wounding could be a stimulus for bone marrow
      derived stem cells to travel to organs and aid in the regeneration of damaged
      tissue.

PMID- 12811817
TI  - The Sp1 transcription factor does not directly interact with the HIV-1 Tat
      protein.
AB  - The role of Sp1 in regulating the trans-activating activity of the human
      immunodeficiency virus type 1 (HIV-1) Tat protein has not yet been clearly
      defined. In fact, studies on the physical and functional interaction between Sp1
      and Tat have yielded contradictory results. Here we investigated whether a
      physical interaction between Sp1 and Tat indeed occurs, exploiting both
      biochemical and genetic techniques that allow detection of direct protein-protein
      interactions. Studies performed with the yeast two-hybrid system indicate that
      Sp1 does not directly interact with the HIV-1 Tat protein. Control experiments
      demonstrated that both proteins are functionally expressed in the yeast cells. In
      vitro binding assays further confirmed that Sp1 does not physically bind Tat.
      These data suggest that in vivo Tat and Sp1 most likely take part of a
      multicomponent complex and thus encourage the search of the molecule(s) which
      mediate Tat-Sp1 interaction.

PMID- 12811818
TI  - Bone morphogenetic protein-7 reduces the severity of colon tissue damage and
      accelerates the healing of inflammatory bowel disease in rats.
AB  - Bone morphogenetic protein-7 (BMP-7) is a growth and differentiation factor and
      belongs to the TGF-beta superfamily of proteins. Previous studies have shown an
      abundant expression of BMP-7 in the developing intestine and an association with
      a perturbed BMP/SMAD downstream signaling leading to a malignant phenotype and
      inflammation in the gut. In the present study, we have evaluated the effect of
      systemically administered recombinant human BMP-7 against trinitrobenzenesulfonic
      (TNBS) acid induced inflammatory bowel disease (IBD) in rats. The TNBS
      administered rats treated with BMP-7 have developed much less severe form of
      colitis based on macroscopic and histological scoring when administered 1.5 h
      before or 24 h after colitis induction. Bioavailability studies in healthy rats
      have revealed that significant portion (3.6%) of i.v. administered BMP-7 is
      targeted for BMP-7 receptors in the stomach and ileum, respectively, suggesting
      its availability to target tissue upon administration. Immunohistochemical and RT
      PCR analyses have shown elevated expression of pro-inflammatory (IL-6, TNF-beta,
      ICAM-1) and pro-fibrogenic (TGF-beta) cytokines, and BMP-7 treatment
      significantly reduced their expression in the intestine; among which the
      suppression of IL-6 appeared to be the most important. Taken together, the
      results of this study suggest that BMP-7 plays an important role in the
      regulation of anti-inflammatory response in the adult gut tissue.

PMID- 12811819
TI  - CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with
      perlecan in regulating the proliferation and differentiation of chondrocytes.
AB  - Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24
      (CTGF/Hcs24) plays important roles in the control of the proliferation and
      differentiation of chondrocytes in vitro. To clarify the mechanisms of regulation
      by CTGF/Hcs24 with respect to cartilage metabolism, we investigated the
      interaction between CTGF/Hcs24 and heparan sulfate proteoglycan perlecan. An
      immunofluorescence study showed that CTGF/Hcs24 was colocalized with heparan
      sulfate and perlecan in human chondrosarcoma-derived chondrocytic cell line HCS
      2/8 in vitro. Northern blot analysis showed that perlecan, syndecan-1, -2, and -4
      transcripts were detected in HCS-2/8 cells. Particularly, expression of the
      perlecan gene increased markedly in HCS-2/8 cells by recombinant CTGF/Hcs24
      (rCTGF/Hcs24) treatment. We also found that CTGF/Hcs24 interacted with perlecan
      from HCS-2/8 cells in vitro. Furthermore, CTGF/Hcs24-stimulated gene expression
      of the aggrecan gene, as well as DNA/proteoglycan synthesis, was diminished when
      HCS-2/8 cells were pretreated with heparinase, indicating that the effects of
      CTGF/Hcs24 on chondrocytes occurred through the interaction between CTGF/Hcs24
      and heparan sulfate on the cells. An in vivo study using mouse growth plate
      revealed that CTGF/Hcs24 produced by hypertrophic chondrocytes was localized from
      the proliferative to the hypertrophic zone, whereas perlecan was predominantly
      localized in the prehyphertrophic zone. Consistent with such findings in vivo,
      the binding of (125)I-rCTGF/Hcs24 to maturing chondrocytes was at higher levels
      than that to chondrocytes in hypertrophic stages. These findings suggest that
      CTGF/Hcs24 produced in the hypertrophic region may act on chondrocytes in the
      proliferative and maturative zone via some heparan sulfate proteoglycan, such as
      perlecan.

PMID- 12811820
TI  - Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in
      NB4 promyelocytic leukemia cells.
AB  - Methylxantine derivative, caffeine, is known to prevent the p53-dependent
      apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase,
      which activates p53 by phosphorylation of the Ser-15 residue. In contrast, it has
      been reported that caffeine induces p53-mediated apoptosis through Bax protein in
      non-small-cell lung cancer cells. Therefore, the effects of caffeine on cellular
      growth in malignant cells are controversial. We investigated the effects of
      caffeine on cell proliferation, cell cycle progression, and induction of
      apoptosis in NB4 promyelocytic leukemia cells containing wild-type p53. Caffeine
      suppressed the cellular growth of NB4 cells in a dose- and time-dependent manner.
      Caffeine induced G(2)/M phase cell cycle arrest in NB4 cells in association with
      the induction of phosphorylation at the Ser-15 residue of p53 and induction of
      tyrosine phosphorylation of cdc2. Expression of Bax protein was increased in NB4
      cells after treatment with caffeine. Interestingly, the antisense
      oligonucleotides for p53 significantly reduced p53 expression and caffeine
      induced G(2)/M phase cell cycle arrest in NB4 cells. These results suggest that
      caffeine induces cell cycle arrest and apoptosis in association with activation
      of p53 by a novel pathway to phosphorylate the Ser-15 residue and induction of
      phosphorylation of cdc 2 in leukemic cells with normal p53.

PMID- 12811821
TI  - Human-derived vascular smooth muscle cells produce angiotensin II by changing to
      the synthetic phenotype.
AB  - We investigated whether vascular smooth muscle cells (VSMC)-derived from human
      produce angiotensin (Ang) II upon change from the contractile phenotype to the
      synthetic phenotype by incubation with fibronectin (FN). Expression of alpha
      smooth muscle (SM) actin, apparent in the contractile phenotype, was decreased by
      FN. Expressions of matrix Gla and osteopontin, apparent in the synthetic
      phenotype, were increased by FN. Ang II measured by radioimmunoassay (RIA) was
      significantly increased in human VSMC by FN. Expression of mRNAs for Ang II
      generating proteases cathepsin D, cathepsin G, ACE, and chymase was increased by
      FN. Expressions of cathepsin D and cathepsin G proteins were also increased by
      FN. Ang I-generating activity, which was inhibited by an aspartyl protease
      inhibitor pepstatin A, was readily detected in the conditioned medium from human
      VSMC. Antisense oligodeoxynucleotides (ODNs) that hybridize with cathepsin D and
      cathepsin G significantly inhibited FN-increased Ang II in conditioned medium and
      cell extracts. In VSMC conditioned medium, FN-induced elevation of Ang II was
      significantly inhibited by temocapril but not by chymostatin. Ang II type 1
      receptor antagonist CV11974 completely, and antisense cathepsin D and cathepsin G
      ODNs partially inhibited the FN-stimulated growth of human VSMC. These results
      indicate that the change of homogeneous cultures of human VSMC from the
      contractile to the synthetic phenotype sequentially increases expression of
      proteases cathepsin D, cathepsin G, and ACE, production of Ang II and productions
      of growth factors, culminating in VSMC proliferation. These findings implicate a
      new mechanism for the pathogenesis of human vascular proliferative diseases.

PMID- 12811822
TI  - Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression
      via TGF-beta in mesangial cells.
AB  - Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid derived from
      fish oil, is efficacious in glomerular diseases where mesangial proliferation is
      a key event. We examined the mechanisms of action of EPA on platelet-derived
      growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose
      dependently inhibited PDGF-stimulated [(3)H]-thymidine incorporation. PDGF
      induced PDGF receptor autophosphorylation, an initial event for PDGF signaling,
      was not affected by 2 micro g/ml EPA. Similarly, PDGF-stimulated activation of
      extracellular signal-regulated kinase (ERK) was not altered. On the other hand,
      EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein
      induction, a critical step for G1/S progression. TGF-beta secretion assessed by
      ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-beta
      antibody inhibited the EPA-induced suppression of [(3)H]-thymidine incorporation
      and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of
      TGF-beta, did not affect EPA's growth inhibitory effect. These results
      demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and
      cyclin D1 expression via TGF-beta.

PMID- 12811823
TI  - Runx1/AML1 hematopoietic transcription factor contributes to skeletal development
      in vivo.
AB  - The requirement of Runx2 (Cbfal/AML3), a runt homology domain transcription
      factor essential for bone formation and osteoblast differentiation, is well
      established. Although Runx2 is expressed in the developing embryo prior to
      ossification, yet in the absence of Runx2 initial formation of the skeleton is
      normal, suggesting a potential redundancy in function of Runx family members.
      Here we addressed expression of the hematopoietic family member Runx1
      (AML1/Cbfa2) in relation to skeletal development using a LacZ knock-in mouse
      model (Runx1(lz/+)). The resulting fusion protein reflects Runx1 promoter
      activity in its native context. Our studies show that Runx1 is expressed by
      prechondrocytic tissue forming the cartilaginous anlagen in the embryo, resting
      zone chondrocytes, suture lines of the calvarium, and in periosteal and
      perichondral membranes of all bone. Runx1 continues to be expressed in these
      tissues in adult mice, but is absent in mature cartilage or mineralized bone.
      However, hyaline cartilage outside the bone environment (trachea, xiphoid
      tissues), and epithelium of many soft tissues (trachea, thyroid, lung, skin) also
      express Runx1. The robust expression of Runx1 in vivo in chondroblasts at sites
      of cartilage growth and in osteoblasts at sites of new bone formation, suggests
      that Runx1 expression may be related to osteochondroprogenitor cell
      differentiation. This observation is further supported by high expression of
      Runx1 in ex vivo cultures of marrow stromal cells and calvarial derived
      osteoblasts from Runx1(lz/+) mice. These data indicate that Runx1 may contribute
      to the early stages of skeletogenesis and continues to function in the progenitor
      cells of tissues that support bone formation in the adult.

PMID- 12811824
TI  - Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.
AB  - We have previously shown that ectopic expression of the ASY/Nogo-B gene induced
      apoptosis in various cancer cell lines. Nogo-A, a splice variant of the ASY, has
      been reported to have an inhibitory effect on neuronal regeneration in the
      central nervous system. To investigate the mechanism of ASY-induced apoptosis or
      inhibition of neuronal regeneration, we cloned a cDNA for the ASY-interacting
      protein from the human cDNA library using the yeast two-hybrid method, and
      obtained a cDNA we designated as ASYIP. The ASYIP protein contains two
      hydrophobic regions and a double lysine endoplasmic reticulum (ER) retrieval
      motif at its C-terminus, which was shown to be identical to RTN3, a reticulon
      family protein of unknown function. We showed that ASY and ASYIP proteins formed
      a complex also in human cells. Mutational analysis indicated that both of the
      hydrophobic regions of the ASYIP protein were required for the association. By
      immunofluorescence analysis, the ASYIP protein was shown to be co-localized with
      ASY in the ER. Characterization of the ASYIP gene may be very useful in
      clarifying the mechanism of ASY-induced apoptosis or Nogo-involved inhibition of
      neuronal regeneration in the central nervous system.

PMID- 12811825
TI  - Growth retardation as well as spleen and thymus involution in latent TGF-beta
      binding protein (Ltbp)-3 null mice.
AB  - The latent TGF-beta binding protein (LTBP)-3 is an extracellular matrix (ECM)
      protein that binds the small latent complex (SLC) of TGF-beta. Disruption of the
      Ltbp-3 gene by homologous recombination in mice yields mutant animals that
      display multiple skeletal abnormalities. In addition, these mice have retarded
      growth. On an inbred 129 SvEv background, half of the Ltbp-3 mutant mice die
      between 3 and 4 weeks after birth. These mice show severe involution of the
      thymus and spleen and a sharp reduction in the numbers of CD4/CD8 double positive
      T-cells in the thymus. The thymus and spleen defect is caused by elevated
      corticosterone levels in the serum and can be reversed by injection of
      aminoglutethimide (AMG), an inhibitor of steroid synthesis. This result indicates
      that the thymus and spleen defect is a secondary defect due to high
      corticosterone levels probably induced by stress of unknown etiology.

PMID- 12811826
TI  - Hyperoxia induces Egr-1 expression through activation of extracellular signal
      regulated kinase 1/2 pathway.
AB  - Early growth response gene (Egr-1) is a stress response gene activated by various
      forms of stress and growth factor signaling. We report that supraphysiologic
      concentrations of O(2) (hyperoxia) induced Egr-1 mRNA and protein expression in
      cultured alveolar epithelial cells, as well as in mouse lung in vivo. The
      contribution of the mitogen-activated protein kinase kinase (MEK)/extracellular
      signal-regulated kinase (ERK), p38 MAPK and PI3-kinase pathways to the activation
      of Egr-1 in response to hyperoxia was examined. Exposure to hyperoxia resulted in
      a rapid phosphorylation of ERK 1/2 kinases in mouse alveolar epithelial cells
      LA4. MEK inhibitor PD98059, but not inhibitors of p38 MAPK or PI3-kinase pathway,
      prevented Egr-1 induction by hyperoxia. The signaling cascade preceding Egr-1
      activation was traced to epidermal growth factor receptor (EGFR) signaling.
      Hyperoxia is used as supplemental therapy in some diseases and typically results
      in elevated levels of reactive oxygen intermediates (ROI) in many lung cell
      types, the organ that receives highest O(2) exposure. Our results support a
      pathway for the hyperoxia response that involves EGF receptor, MEK/ERK pathway,
      and other unknown signaling components leading to Egr-1 induction. This forms a
      foundation for analysis of detailed mechanisms underlying Egr-1 activation during
      hyperoxia and understanding its consequences for regulating cell response to
      oxygen toxicity.

PMID- 12811827
TI  - Mda-7/IL-24 induces apoptosis of diverse cancer cell lines through JAK/STAT
      independent pathways.
AB  - Experimental evidence documents that the MDA-7/IL-24 protein (an IL-10 family
      cytokine) binds to IL-20 and IL-22 receptor complexes resulting in the activation
      of JAK/STAT signaling pathways. Recent published reports utilizing human blood
      derived primary lymphocytes have provided additional confirmatory evidence
      relating to the cytokine properties of this molecule. A notable attribute of mda
      7/IL-24 is its cancer cell-specific apoptosis inducing capacity, which currently
      remains incompletely understood. Treatment with distinctive tyrosine kinase
      inhibitors (Genistein and AG18) or a JAK-selective inhibitor (AG490) did not
      prevent Ad.mda-7 induced apoptosis in diverse cell lines. In addition, there is
      no apparent correlation between patterns of expression of IL-20R1, IL-20R2, and
      IL-22R mRNA and susceptibility to Ad.mda-7 in different cell lines. Furthermore,
      Ad.mda-7 is able to induce killing in STAT/JAK deficient cells. In contrast,
      treatment with the p38(MAPK) selective inhibitor SB203580, partially inhibited
      apoptosis induced by Ad.mda-7 in different cell lines. These results demonstrate
      for the first time that signaling events leading to susceptibility to Ad.mda-7
      induced apoptosis, might be tyrosine kinase independent and can thus be
      distinguished from its cytokine function related properties mediated by the IL
      20/IL-22 receptor complexes that require JAK/STAT kinase activity.

PMID- 12811828
TI  - Modulation of PAI-1 and proMMP-9 syntheses by soluble TNFalpha and its receptors
      during differentiation of the human monocytic HL-60 cell line.
AB  - During phorbol ester-induced differentiation of HL-60 monocytic cells, tumor
      necrosis factoralpha (TNFalpha) synthesis and secretion are increased, which
      contributes to the autocrine regulation of TNFalpha-responsive genes. We
      investigated how, during phorbol ester-induced differentiation of HL-60 cells,
      the secreted TNFalpha modulated plasminogen activator inhibitor type I (PAI-1)
      and gelatinase B (MMP-9) syntheses, two proteins involved in pericellular
      proteolysis. The differentiation-induced release of TNFalpha, was abolished by
      the hydroxamate-based matrix metalloproteinase (MMP) inhibitor, RU36156. RU36156
      or a neutralizing anti-TNFalpha significantly down-regulated PAI-1 synthesis
      exclusively during the early phases of differentiation (from promyelocyte to
      monocytic-like cells), which underlined the activating role of autocrine TNFalpha
      during this time range. As cells progressed to monocyte/macrophage phenotype,
      they still released TNFalpha, but RU36156 or anti-TNFalpha no longer had an
      effect on PAI-1 synthesis. This lack of effect was not due to a default of
      TNFalpha signaling since PAI-1 synthesis was still stimulated in response to
      exogenous TNFalpha. TNFalpha receptor RI was also actively released and was shown
      to reduce TNFalpha activity which may account for the inability of soluble
      TNFalpha to up-regulate PAI-1 synthesis. In later mature stage, cells became
      susceptible to exogenous TNFalpha-induced apoptosis and rapidly lost their
      ability to respond to TNFalpha. The MMP-9 synthesis followed similar regulation
      as PAI-1. Isolated human blood monocytes-derived macrophages behave like HL-60
      derived macrophages. In conclusion, these results show that during leukocyte
      differentiation, time windows exist during which the autocrine TNFalpha is active
      and then down-regulated by RI, which may temper a continuous up-regulation of the
      synthesis of proteins involved in pericellular proteolysis.

PMID- 12811829
TI  - Chromatin sphingomyelin changes in cell proliferation and/or apoptosis induced by
      ciprofibrate.
AB  - It has been shown that neutral-sphingomyelinase and sphingomyelin-synthase
      activities are present in chromatin and they modify the sphingomyelin (SM)
      content. The activity of the first enzyme is stimulated and the second inhibited,
      when the hepatocytes enter into the S-phase after partial hepatectomy, thus
      suggesting that ceramide may have a pivotal role in cell proliferation. An
      opposite function was attributed to ceramide in hepatocytes which undergo
      apoptosis after lobular ligature. In order to clarify this point, a model was
      developed in which the same liver cells undergo proliferation followed by induced
      apoptosis. To this purpose, the rats were treated for 7 days with ciprofibrate
      and then left without treatment for 4 days. During the treatment, the peroxisome
      enzyme markers increase their activity and the number of proliferating cells
      increases, reaching a maximum after 3 days of treatment, as shown by the number
      of cells positive for the proliferating cell nuclear antigen. At the same time,
      the chromatin sphingomyelinase activity reaches the maximum, while a similar
      increase is not found in the cytoplasm or in the isolated nuclei. On the
      contrary, SM-synthase activity is depressed in chromatin, but not in the nuclei
      in which a peak is shown after 3 days of ciprofibrate treatment. After drug
      withdrawal, the hepatocytes undergo apoptosis as confirmed by the increase of Bax
      and tissue transglutaminase (tTGase) expression; the chromatin SM increases as a
      consequence of an increase of SM-synthase activity. It can be hypothesised that
      chromatin SM may have a role in cell duplication by influencing the chromatin
      structure stability.

PMID- 12811830
TI  - Biphasic effects of 17-beta-estradiol on expression of occludin and
      transendothelial resistance and paracellular permeability in human vascular
      endothelial cells.
AB  - Tight junctions govern the paracellular permeability of endothelial and
      epithelial cells. Aberrations of tight junction function are an early and key
      event during the vascular spread of cancer and inflammation. This study sought to
      determine the role of estrogen in the regulation of tight junctions and
      expression of molecules making tight junctions in endothelial cells. Human
      endothelial cell, HECV, which express ER-beta but not ER-alpha was used. 17-beta
      estradiol induced a concentration- and time-dependent biphasic effect on tight
      junction. At 10(-9) and 10(-6) M, it decreased the level of occludin and
      increased in paracellular permeability of HECV cells, but at 10(-12) M it
      decreased in paracellular permeability and increased the level of occludin. The
      transendothelial electrical resistance (TER), however, was reduced by 17-beta
      estradiol at lower concentrations (as low as 10(-12) M). Furthermore, the time
      dependent biphasic effect was observed over a period of 4 days, with the first
      reduction of TER seen within 15 min and the second drop occurring 48 h after 17
      beta-estradiol treatment. It was further revealed that protein and mRNA levels of
      occludin, but not claudin-1 and -5, and ZO-1, were reduced by 17-beta-estradiol,
      in line with changes of TER. This study shows that 17-beta-estradiol can induce
      concentration- and time-related biphasic effects on tight junction functions
      expression of occludin in endothelial cells and that this perturbation of tight
      junction functions may have implications in the etiology of mastalgia and the
      vascular spread of breast cancer.

PMID- 12811831
TI  - Angiotensin II activates extracellular signal regulated kinases via protein
      kinase C and epidermal growth factor receptor in breast cancer cells.
AB  - Angiotensin II (Ang II) induces, through AT1, intracellular Ca(2+) increase in
      both normal and cancerous breast cells in primary culture (Greco et al., 2002
      Cell Calcium 2:1-10). We here show that Ang II stimulated, in a dose-dependent
      manner, the 24 h-proliferation of breast cancer cells in primary culture, induced
      translocation of protein kinase C (PKC)-alpha, -beta1/2, and delta (but not 
      epsilon, -eta, -theta, -zeta, and -iota), and phosphorylated extracellular
      regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were
      blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had
      mitogenic effects on serum-starved breast cancer cells since induced cell
      proliferation after 24 h and phosphorylation of ERK1/2. The Ang II-induced
      proliferation of breast cancer cells was reduced by (a) Go6976, an inhibitor of
      conventional PKC-alpha and -beta1, (b) AG1478, an inhibitor of the tyrosine
      kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2-diacylglycerol
      sensitive PKCs achieved by phorbol 12-myristate 13-acetate (PMA). A complete
      inhibition of the Ang II-induced cell proliferation was achieved using the
      inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK),
      PD098059, or using Go6976 together with AG1478. These results indicate that in
      human primary cultured breast cancer cells AT1 regulates mitogenic signaling
      pathways by two simultaneous mechanisms, one involving conventional PKCs and the
      other EGFR transactivation.

PMID- 12811832
TI  - Phenotype modulation in cultures of vascular smooth muscle cells from diabetic
      rats: association with increased nitric oxide synthase expression and superoxide
      anion generation.
AB  - Proliferative modification of vascular smooth muscle cell (vSMC) and impaired
      bioavailability of nitric oxide (NO) have both been proposed among the mechanisms
      linking diabetes and atherosclerosis. However, diabetes induced modifications in
      phenotype and nitric oxide synthase(s) (NOS) expression and activity in vSMC have
      not been fully characterized. In this study, cell morphology, proliferative
      response to serum, alpha-SMactin levels, eNOS expression and activity, cGMP
      intracellular content, and superoxide anion release were measured in cultures of
      vSMC obtained from aorta medial layer of ten diabetic (90% pancreatectomy, DR)
      and ten control (sham surgery, CR) rats. Vascular SMC from DR showed a less
      evident "hill and valley" culture morphology, increased growth response to serum,
      greater saturation density, and lower levels of alpha-SMactin. In the same cells,
      as compared to CR cells, eNOS mRNA levels and NOS activity were increased, while
      intracellular cGMP level was lower and superoxide anion production was
      significantly greater. These data indicate that chronic hyperglycemia might
      induce, in the vascular wall, an increased number of vSMC proliferative clones
      which persist in culture and are associated with increased eNOS expression and
      activity. However, upregulation of eNOS and increased NO synthesis occur in the
      presence of a marked concomitant increase of O(2-) production. Since NO
      bioavailability, as reflected by cGMP levels, was not increased in DR cells, it
      is tempting to hypothesize that the proliferative phenotype observed in DR cells
      is associated with a redox imbalance responsible quenching and/or trapping of NO,
      with the consequent loss of its biological activity.

PMID- 12811833
TI  - Androgen regulation of FLICE-like inhibitory protein gene expression in the rat
      prostate.
AB  - In hope of eventually identifying defects in human prostatic neoplasias that
      render them insensitive to anti-androgen therapy, we have examined the regulation
      of components of ligand-induced cell death pathways during castration-induced
      regression of the prostate. Rat prostates were obtained after surgical castration
      with or without subsequent androgen replacement. The mRNA levels of genes
      encoding components of the apoptotic pathway were measured from individual
      prostates. Whole prostates 1-10 days after castration did not show a significant
      change in mRNA levels encoding either Fas or FasL, which some studies suggest are
      necessary for regression to occur. However, the mRNA encoding a catalytically
      inactive cysteinyl aspartate-specific protease (caspase) analog, FLICE-like
      inhibitor protein (FLIP), decreases during the first day following castration. In
      the most apoptotically responsive ventral lobe of the rat prostate, the reduction
      in FLIP mRNA levels is evident within 12 h of castration. The mRNA levels of the
      principal target of FLIP inhibition, caspase-8, do not change during the period
      preceding the onset of detectable DNA fragmentation. Androgen administration to
      castrated rats reverses prostate regression, and restores FLIP mRNA to normal
      levels. By acting as an inhibitor of caspase-8, FLIP may protect prostatic
      epithelium from apoptosis. Androgen withdrawal, by reducing FLIP mRNA levels,
      might leave the cells vulnerable to as yet unidentified cell death signals.

PMID- 12811834
TI  - Geldanamycin inhibits migration of glioma cells in vitro: a potential role for
      hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion.
AB  - Focal adhesion kinase (FAK) and hypoxia-inducible factor (HIF-1alpha) are both up
      regulated in glioblastoma multiforme (GBMs), particularly in invasive zones.
      Because FAK may play an important role in the invasion of glioma cells into the
      surrounding brain, we sought an agent that causes down-regulation of FAK
      phosphorylation as a potential inhibitor of brain tumor invasion and growth.
      Geldanamycin (GA), a benzoquinone ansamycin antibiotic, binds to heat shock
      protein 90 (Hsp90) and interferes with its function. GA inhibits the
      proliferation of various non-glial cells and has anti-tumor activity. Moreover,
      GA blocks HIF-regulated transcription of VEGF and inhibits the VEGF-induced
      phosphorylation of FAK and migration of endothelial cells. Here, we tested the
      effect of GA on glioma cell migration in vitro and its potential to down-regulate
      HIF-1alpha induction. Our results demonstrate that GA (i) decreases U87MG, LN229,
      and U251MG glioma cell migration; (ii) reduces cell migration independent of p53
      and PTEN status; (iii) prevents migration at non-toxic concentrations; (iv)
      reduces phosphorylation of FAK; and (v) inhibits cobalt chloride (CoCl(2))
      mediated induction of HIF-1alpha in glioma cells. To the best of our knowledge,
      this is the first report showing that GA can inhibit phosphorylation of FAK
      concomitant with a decrease in cellular migration. One of the most clinically
      relevant aspects of this study is that GA interferes with the induction of HIF
      1alpha that has been linked with glioma cell migration and angiogenesis. Given
      the fact that GA is a small lipophilic molecule capable of penetrating the blood
      brain barrier together with the data presented here provide a strong rationale
      for its use or its analogues in the treatment of highly invasive GBMs.

PMID- 12811835
TI  - Folate uptake in the human intestine: promoter activity and effect of folate
      deficiency.
AB  - The intestinal folate absorption process occurs via a specialized mechanism that
      involves the reduced folate carrier (RFC). In humans, multiple variants of the
      hRFC (driven by multiple promoters) have been identified with variant I being the
      prominent form expressed in the intestine. While it is known that promoter B (pB)
      of hRFC drives the expression of this variant, little is known about the minimal
      region required for basal activity of this promoter in human intestinal
      epithelial cells. Also not known is whether folate absorption in the human
      intestine is up-regulated during folate deficiency (as occur in animal studies),
      and if so, whether transcriptional mechanisms via activation of hRFC pB are
      involved in such regulation. To address these issues, we have used deletion
      constructs of the hRFC pB and determined their activity in two human intestinal
      epithelial cell lines: the colon-derived Caco-2 cells, and the duodenum-derived
      HuTu-80 cells. Our results showed that activity of hRFC pB to be significantly
      higher in Caco-2 cells compared to HuTu-80 cells, a finding that corresponds with
      a higher level of folate uptake and endogenous hRFC mRNA levels in the former
      compared to the latter cell type. The minimal region required for basal activity
      of hRFC pB in Caco-2 cells was found to be encoded in a sequence between -1088
      and -1043, while in HuTu-80 cells it was encoded in a sequence between -1431 and 
      1088. Growing Caco-2 cells in a folate deficient medium led to a significant and
      specific up-regulation in folate uptake. This up-regulation was associated with a
      parallel increase in hRFC protein and mRNA levels, and in the activity of hRFC
      pB. The most responsive sequence of pB to the effect of folate deficiency was
      found to be encoded in a sequence between -2016 and -1431, i.e., outside the
      minimal region of the pB. These results show that different minimal regions for
      hRFC pB are utilized by different intestinal epithelial cells. In addition,
      folate-deficiency was found to up-regulate folate uptake by human intestinal
      epithelial cells and that this regulation involves activation of hRFC pB.

PMID- 12811836
TI  - Toll-like receptors: networking for success.
AB  - The innate immune system is essential for host defense and is responsible for
      early detection of potentially pathogenic microorganisms. Upon recognition of
      microbes by innate immune cells such as macrophages and dendritic cells, diverse
      signaling pathways are activated that combine to define inflammatory responses
      that direct sterilization of the threat and/or orchestrate development of the
      adaptive immune response. Innate immune signaling must be carefully controlled,
      and regulation comes in part from interactions between activating and inhibiting
      signaling receptors. Toll-like receptors (TLR) have recently emerged as key
      receptors responsible for recognizing specific conserved components of microbes
      including lipopolysaccharides from Gram-negative bacteria, CpG DNA, and
      flagellin. Full activation of inflammatory responses by TLR may require the
      assembly of receptor signaling complexes including other transmembrane proteins
      that may influence signal transduction. In addition to TLR, many additional
      receptors participate in innate recognition of microbes, and recent studies
      demonstrate strong interactions between signaling through these receptors and
      signaling through TLR. Useful models for these interacting signaling pathways are
      now emerging and should pave the way for understanding the molecular mechanisms
      that drive the rich diversity of inflammatory responses.

PMID- 12811837
TI  - Triggering of Toll-like receptors modulates IFN-gamma signaling: involvement of
      serine 727 STAT1 phosphorylation and suppressors of cytokine signaling.
AB  - Microbial stimuli activate cells of the innate immune system by triggering Toll
      like receptors (TLR). Activation of macrophages and dendritic cells is further
      enhanced by secondary signals like IFN-gamma. Here we analyzed the interplay of
      IFN-gamma and TLR signaling in cells of the innate immune system. Using a STAT1
      dependent reporter construct we show that IFN-gamma signaling can be enhanced as
      well as inhibited by simultaneous stimulation with either defined TLR agonists or
      whole-bacterial lysates. Short costimulation resulted in the amplification of IFN
      gamma signaling and was attributable to the p38 mitogen-activated protein kinase
      (MAPK)-dependent phosphorylation of signal transducer and activator of
      transcription (STAT)1 on serine 727. In contrast, prolonged co-incubation as well
      as pre-incubation with TLR agonists led to an inhibition of IFN-gamma signaling.
      TLR triggering induced expression of suppressor of cytokine signaling (SOCS)-1,
      SOCS-3 and cytokine-inducible SH2 domain-containing protein (CIS). Overexpression
      of SOCS-1 and, to a lesser extend, of SOCS-3 and CIS inhibited IFN-gamma
      signaling as measured by activation of STAT1. Moreover, pre-incubation with TLR
      dependent stimuli impaired IFN-gamma-induced MHC class II regulation but enhanced
      CD40 and CD86 expression. Taken together, the results indicate a tight interplay
      between TLR and IFN-gamma signaling pathways which involve induction of SOCS
      proteins and serine phosphorylation of STAT1.

PMID- 12811838
TI  - "Bystander polarization" of CD4+ T cells: activation with high-dose IL-2 renders
      naive T cells responsive to IL-12 and/or IL-18 in the absence of TCR ligation.
AB  - Responsiveness of CD4+ T cells to the IFN-gamma-inducing cytokines IL-12 and IL
      18 is generally thought to be acquired only after stimulation via the TCR. We
      report herein that stimulation of naive CD4+ T cells with high-dose IL-2 (1000
      U/ml) renders these cells responsive to IL-12 and/or IL-18 without a requirement
      for TCR ligation. Naive CD4+CD62L+ Tcells from normal C57BL/6 mice or from
      DO11.10/Rag2(-/- )OVA-specific TCR-transgenic mice secreted substantial amounts
      of IFN-gamma when stimulated concurrently with high-dose IL-2 plus IL-12 or IL
      18. mRNA encoding both chains of the IL-12 and the IL-18 receptors was expressed
      by CD4+ T cells after stimulation with high-dose IL-2. Furthermore, anti-CD3
      induced IL-12/IL-18 responsiveness was fully abrogated in the presence of
      cyclosporin A whereas IL-2-induced IL-12/IL-18 responsiveness was not,
      reminiscent of the previously reported IL-12+IL-18 innate pathway of T cell
      activation. Lastly, after stimulation with IL-2+IL-12, naive CD4+ T cells from
      DO11.10/Rag2(-/- )mice exhibited polarization towards a Th1 phenotype (high IFN
      gamma but no IL-4) during secondary stimulation with immobilized anti-CD3. We
      have coined the term "bystander polarization" to describe this phenomenon and we
      speculate that bystander polarization of naive CD4+ T cells may occur in vivo
      during strong antigen-specific immune responses.

PMID- 12811839
TI  - Development of protective immunity against cutaneous leishmaniasis is dependent
      on STAT1-mediated IFN signaling pathway.
AB  - Although STAT1-dependent signaling mediates biological functions of IFN
      alpha/beta and IFN-gamma, recent reports indicate that STAT1-independent IFN
      signaling also regulates expression of several genes. To determine the roles of
      STAT1-dependent and -independent IFN signaling in the regulation of immunity
      during cutaneous leishmaniasis, we studied the course of Leishmania major
      infection in resistant C57BL/6 mice lacking the STAT1 gene. While L. major
      infected STAT1(+/+) mice resolved their lesions, STAT1(-/-) mice developed large
      lesions containing significantly more parasites. Moreover, the inability of
      STAT1(-/-) mice to control L. major infection was due to the lack of Th1
      development associated with reduced production of IL-12, IFN-gamma and nitric
      oxide. Although STAT1(-/-) mice produced more IL-4 and total IgE than STAT1(+/+)
      mice later during infection, these differences were not significant.
      Nevertheless, at these time points lymph node cells from STAT1(-/-) mice produced
      significantly more IL-10. Finally, STAT1(-/-) mice were also susceptible to low
      dose L. major infection. Thesefindings demonstrate that STAT1-mediated IFN
      signaling is indispensable for the development of protective immunity against
      cutaneous L. major infection. Moreover, they also suggest that the protective
      role of STAT1-mediated signaling is due to its ability to induce Th1 development
      during infection with this parasite.

PMID- 12811840
TI  - Selective enhancement of B cell antigen receptor-mediated antigen presentation by
      treatment with transforming growth factor-beta.
AB  - TGF-beta1 was examined for the ability to regulate Ag-presentation by B cells,
      using A20-HL B lymphoma cells bearing TNP-specific IgM receptors. Treatment of
      A20-HL cells with TGF-beta1 at 1 ng/ml, a concentration that inhibited
      proliferation, enhanced presentation of Ag internalized via surface IgM (sIgM),
      but not via fluid-phase pinocytosis. TGF-beta1-treatment slightly enhanced
      surface expression of sIgM, but not of MHC class II molecules. The treatment
      accelerated recovery of sIgM expression after its removal by ligation with TNP
      OVA, and induced prolonged intracellular residence of TNP-OVA internalized via
      sIgM, which co-localized with intracellular MHC class II molecules. TGF-beta1
      treatment increased accumulation of newly synthesized intracellular MHC class II
      molecules that were localized in compartments positive for lysosome-associated
      membrane protein 1, although cellular protein synthesis was decreased by the
      treatment. The accumulated intracellular MHC class II molecules were triggered to
      the cell surface by ligation of sIgM. Finally, TGF-beta1-treatment induced
      Igalpha-phosphorylation in response to lower concentrations of TNP-OVA. On the
      basis of these findings, we conclude that TGF-beta1-treatment of A20-HL cells
      selectively enhances the ability to present Ag internalized via sIgM, not via
      fluid-phase pinocytosis, through accelerating sIgM recovery, increasing
      accumulation of intracellular MHC class II molecules and enhancing the ability of
      sIgM ligation to induce Igalpha-phosphorylation.

PMID- 12811841
TI  - Intrathymic NKT cell development is blocked by the presence of alpha
      galactosylceramide.
AB  - NKT cell development takes place in the thymus, beginning when these cells branch
      away from CD4+CD8+ mainstream thymocytes upon expression of the Valpha14Jalpha18
      T cell receptor (TCR) and recognition of the CD1d molecule. Although NKT cells
      express an invariant TCR alpha chain, the diverse TCR beta expression leaves open
      the possibility that the development of these cells is shaped by glycolipid
      antigen recognition in the context of CD1d. Here, we show that the presence of an
      agonist glycolipid ligand, alpha-galactosylceramide, while NKT cells are
      developing in vitro or in vivo, specifically ablates their development. In
      contrast, the delayed introduction of this compound in vitro or in vivo, after
      NKT cells have developed, does not deplete these cells. These data indicate that
      NKT cells pass through a developmental window where they are susceptible to TCR
      mediated negative selection, and suggest that NKT cells with a potentially high
      level of self reactivity can be removed from the NKT cell repertoire before they
      exit the thymus.

PMID- 12811842
TI  - EBF-regulating Pax5 transcription is enhanced by STAT5 in the early stage of B
      cells.
AB  - Pax5 is an essential transcription factor for B cell development, and it is
      reported that Pax5 expression was reduced in the IL-7 receptor (IL-7R) knockout
      mouse. To investigate whether signals from the IL-7R regulate Pax5 transcription,
      we searched the consensus sequence of signal transducers and activators of
      transcription (STAT) in the Pax5 promoter region, since STAT is one of the
      components of cytokine signal transduction. A STAT-binding motif, termed SBM, was
      identified at 1,118 bp upstream of the transcriptional start site, and SBM
      completely overlapped with the binding site for early B cell factor (EBF). STAT5
      was phosphorylated in the presence of IL-7 in the IL-7-dependent preB cell line,
      PreBR1, and phosphorylated-STAT5 as well as EBF was found to bind to the SBM.
      Moreover, we also revealed STAT5 binding to SBM in PreBR1 cells by chromatin
      immunoprecipitation assay. Transient co-transfection of reporter genes together
      with expression vectors of a constitutive active form of STAT5 and EBF into
      NIH3T3 cells demonstrated that STAT5 enhanced EBF-regulating transcription. Our
      results suggest that STAT5 phosphorylated by IL-7 can directly up-regulate Pax5
      transcription in early B cells.

PMID- 12811843
TI  - Activation of invariant NKT cells by alphaGalCer administration protects mice
      from MOG35-55-induced EAE: critical roles for administration route and IFN-gamma.
AB  - Invariant NKT (inv. NKT) cells co-express an invariant alpha beta T cell receptor
      and the NK receptor NK1.1 and, upon CD1d-restricted recognition of the
      glycosphingolipid antigen alpha-galactosyl ceramide (alphaGalCer), secrete large
      amounts of regulatory cytokines. We investigated whether alphaGalCer-dependent
      activation of inv. NKT cells protects from experimental autoimmune
      encephalomyelitis (EAE), an immune-mediated disease of the central nervous system
      mimicking multiple sclerosis, induced in C57BL/6 mice by the myelin
      oligodendrocyte glycoprotein (MOG) encephalitogenic peptide aa 35-55. alphaGalCer
      was administered at the time of immunization s.c., mixed with complete Freund's
      adjuvant and MOG35-55 peptide, or administered i.p., diluted in PBS. EAE onset
      was delayed and disease severity was decreased only when alphaGalCer was s.c.
      administered. The protective effect of s.c. administration of alphaGalCer was
      associated with a markedly enhanced IFN-gamma production by liver-confined inv.
      NKT cells which, in turn, suppressed Th1-cytokine production and fostered
      secretion of IL-10 from MOG35-55-specific T cells. In vivo neutralization of IFN
      gamma, but notIL-4, reversed the protective effect induced by s.c. administration
      of alphaGalCer, further confirming the critical regulatory role exerted by IFN
      gamma-producing inv. NKT cells. Our results indicate that alphaGalCer, properly
      administered, may elicit an inv. NKT-cell-mediated suppressive effect on the
      effector function of encephalitogenic T cells; this effect is able to ameliorate
      autoimmunedemyelination.

PMID- 12811844
TI  - "Bystander" recruitment of systemic memory T cells delays the immune response to
      respiratory virus infection.
AB  - The concept of heterologous T cell immunity postulates that nonspecific memory T
      cells recruited and reactivated in the context of an unrelated virus infection
      may contribute to protective antiviral immunity. Pulmonary infection with
      respiratory syncytial virus (RSV) of mice immune to lymphocytic choriomeningitis
      virus (LCMV) leads to substantial recruitment of systemic LCMV-specific memory
      CD8 T cells to the lung. Using a sensitive TCR-transgenic model, we show that
      such "bystander" recruitment to the RSV-infected lung could induce a single round
      of cell division among LCMV-specific T cells. However, it did not change their
      activation status as assessed by expression of surface markers, the extent or
      kinetics of IFN-gamma production and cytolytic effector function.
      Moreover,recruitment of LCMV-specific bystander T cells not only failed to
      enhance immunity to RSV, but significantly delayed virus elimination and slightly
      enhanced RSV-induced weight loss in non-transgenic BALB/c mice. This correlated
      with a delay in the recruitment of RSV-specific T cells to the lung. These data
      show that bystander recruitment of heterologous T cells is not necessarily
      accompanied by bystander activation. More importantly, bystander recruitment of
      systemic memory T cells can impair antiviral immunity, presumably by interference
      with the recruitment of specific T cells.

PMID- 12811845
TI  - Exacerbation of experimental autoimmune encephalomyelitis in rodents infected
      with murine gammaherpesvirus-68.
AB  - Viral infections have long been suspected to play a role in the pathogenesis of
      multiple sclerosis. In the present study, two different rodent models of
      experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the
      ability of murine gammaherpesvirus-68 (gammaHV-68) to exacerbate development of
      neurological symptoms. SJL mice received UV-inactivated gammaHV-68 or
      intranasalgammaHV-68, followed by immunization against proteolipid-protein
      peptide 139-151. Infected mice became moribund within 10 days post-immunization,
      whereas mice exposed to UV-inactivated gammaHV-68 recovered. In the second model,
      Lewis rats were exposed to UV-inactivated gammaHV-68 or to gammaHV-68, followed
      by passive transfer of encephalitogenic T lymphocytes specific for myelin basic
      protein. Consistently, infected rats had higher clinical scores, and this result
      was observed during acute or latent gammaHV-68 infection. It is unlikely that
      this gammaHV-68-induced exacerbation was due to significant viral replication
      within the central nervous system since nested PCR, viral plaque assays, and
      infectious-centers assays demonstrated no detectable virus in spinal cords or
      brains of infected rodents undergoing EAE. Taken together, these studies
      demonstrate increased clinical symptoms of EAE in rodents infected by a
      gammaherpesvirus that has a limited ability to invade the central nervous system.

PMID- 12811846
TI  - Cell-surface bound pertussis toxin induces polyclonal T cell responses with high
      levels of interferon-gamma in the absence of interleukin-12.
AB  - Pertussis toxin (PTx), an exotoxin produced by Bordetella pertussis, has long
      been used as a mucosal adjuvant. We examined the T cell stimulatory properties of
      PTx in order to dissect its mechanisms of adjuvanticity. PTx or the B-oligomer of
      PTx (PTxB) failed to activate purified murine CD4+ or CD8+ T cells, as measured
      by a lack of proliferation or expression of early T cell activation markers.
      However, these T cells proliferated extensively in response to the toxin in the
      presence of syngeneic DC, and proliferation was accompanied by a high level of
      IFN-gamma production in the absence of IL-12. Interestingly, such responses were
      independent of signals mediated by MHC-TCR interaction. Both PTx and PTxB were
      found to bind stably to the surface of DC, and increased the adherence of DC to
      surrounding cells. These data suggest that polyclonal T cell responses mediated
      by the toxin are likely to be caused by the toxin bound on the surface of APC,
      either cross-linking cell surface molecules on T cells, or directly stimulating T
      cells together with the co-stimulatory molecules expressed on APC. B. pertussis
      may use this toxin as a mechanism to evade a specific immune response.

PMID- 12811847
TI  - Characterization of the B cell response of patients with anti-liver cytosol
      autoantibodies in type 2 autoimmune hepatitis.
AB  - Anti-liver cytosol type 1 (LC1) autoantibody is detected in 30% of sera from
      patients with type 2 autoimmune hepatitis (AIH), and is the only circulating
      autoantibody in 10% of cases. Human formiminotransferase cyclodeaminase (FTCD)
      has been shown to be the specific liver antigen recognized by anti-LC1
      autoantibodies. The aim of this study was to identify the dominant epitope on
      human FTCD and to analyze antigenic-site sequences for clues on the development
      of AIH. Recombinant proteins and peptides covering the entire cDNA of human FTCD
      were tested against anti-LC1 autoantibodies. Conformational epitopes were found
      throughout the protein but linear epitopes were found exclusively in the C
      terminal 146 amino acids. Two groups of sera with different reactivities were
      found: 69%of the sera recognized two specific linear epitopes at positions 428
      434 (NTPEEKD) and 440-447 (LQEGLRRA) of human FTCD; others reacted only with a
      discontinuous epitope between the amino acids at position 395 and 528. FTCD
      autoantibody production is thus a polyclonal-antigen-driven B cell response.
      Autoantibodies against conformational or discontinuous epitopes were found in all
      patients and two-thirds also recognized linear epitopes on human FTCD.

PMID- 12811848
TI  - Induction of T-cell-mediated skin disease specific for antigen transgenically
      expressed in keratinocytes.
AB  - Transgenic mice were generated to establish an animal model for T-cell-mediated
      autoimmune skin disease. A membrane-bound form of OVA (mOVA) was specifically
      expressed under the control of the keratin 5 (K5) promoter in the epidermal and
      hair follicular keratinocytes of mice. Syngeneic, wild-type mice rejected the
      skin grafts of K5-mOVA mice with the generation of OVA-specific CTL. To study the
      CTL response against K5-mOVA skin, we used OT-I transgenic mice, which produce
      K(b)-restricted, OVA-specific CD8+ T cells. Accelerated rejection of K5-mOVA skin
      was demonstrated when transplanted onto OT-I mice. Furthermore, OT-I cells, when
      adoptively transferred into K5-mOVA mice, underwent activation and vigorous
      proliferation in the skin-draining lymph nodes. A bone-marrow-reconstitution
      assay demonstrated that K(b) presentation by bone-marrow-derived cells, but not
      epithelial cells, was required for this response, indicating that cross-priming
      was the basis for immunity in this model. Finally, transferred OT-I cells,
      activated by cross-priming, targeted the skin of K5-mOVA mice, resulting in
      development of skin lesions that were reminiscent of toxic epidermal necrolysis.
      We conclude that our system provides a useful model for autoimmune skin diseases
      and will aid understanding of the pathomechanism of drug eruption, viral
      exanthema, and graft-versus-host disease.

PMID- 12811849
TI  - Naive and memory B cells respond differentially to T-dependent signaling but
      display an equal potential for differentiation toward the centroblast-restricted
      CD77/globotriaosylceramide phenotype.
AB  - Resting (CD38(low)) tonsillar B cells differentiate to express the centroblast
      restricted CD77/globotriaosylceramide antigen on high-level engagement of CD154.
      As the CD38(low) population comprises both naive and memory subsets, we wished to
      compare the propensity of each to develop this germinal center phenotype;
      particularly as the capacity of memory B cells to re-enter afollicular reaction
      remains unclear. Resting B lymphocytes were therefore separated into CD27(-)IgA(
      )IgG(-) and IgD(-) fractions to generate subsets enriched for naive and memory
      cells, respectively. Following stimulation via BCR and/or CD40 - surrogate
      signals for B cells engaged in T-dependent signaling - differences between the
      two subsets were seen in the kinetics and/or magnitude of responses such as entry
      into DNA synthesis, induction of the costimulatory molecules CD80 and CD86; up
      regulation of CD23, and changes in BCL-6 mRNA expression. Nevertheless, naive and
      memory cells revealed a nigh identical capacity for acquiring CD77: both appeared
      equally sensitive in this regard, with high-level CD40 engagement via cell-bound
      CD154 being required for both subsets to achieve the hallmark centroblast
      phenotype. These findings suggest that, provided with the opportunity to
      encounter cell membrane CD154 in abundance, both naive and memory B cells display
      the potential to be diverted towards a germinal center pathway of
      differentiation.

PMID- 12811850
TI  - T cell-specific gene targeting reveals that alpha4 is required for early T cell
      development.
AB  - Alpha4-mediated signaling is involved in a variety of functions in mammalian
      cells. To determine whether this is true for immunocompetent cells, we generated
      mutant (Lck-alpha4-) mice in which the alpha4 gene was deleted in a T cell
      specific manner using the Cre/loxP system. These mice showed impaired early T
      cell development. Thymi at most ages were small and their architecture was
      disorganized. This defect was not due to increased thymocyte apoptosis but to
      decreased cell proliferation. T cell development was found to be severely
      arrested at the CD4/CD8 double-negative 3 stage and the thymus contained very few
      double-positive or single-positive (SP) mature thymocytes. The mutant thymocytes
      showed impaired proliferative responses to anti-CD3 monoclonal antibody (mAb)
      stimulation or to the cytokines IL-2, IL-1 or TNF. In the spleen, the numbers of
      mature SP T cells were decreased and their proliferative responses to anti-CD3
      plus IL-2 or to anti-CD28 mAb were impaired. A severe impairment of CD3-induced
      expression of CD25 was also observed. These data suggest that alpha4 plays a
      critical role in the proliferation of thymocytes, which is necessary for early T
      cell development.

PMID- 12811851
TI  - Paradoxical effects of arthritis-regulating chromosome 4 regions on myelin
      oligodendrocyte glycoprotein-induced encephalomyelitis in congenic rats.
AB  - Immunoregulatory gene loci in different organ-specific inflammatory diseases
      often co-localize. We here studied myelin oligodendrocyte glycoprotein (MOG)
      induced EAE in rat strains congenic for arthritis-regulating genome regions on
      chromosome 4. We used congenic rats with a 70-centimorgan (cM) fragment from the
      EAE- and arthritis-resistant PVG.1AV1 rat strain on the arthritis- and EAE
      permissive Dark Agouti (DA) rat background. In addition, we evaluated three
      recombinant strains, C4R1-C4R3, which overlap with arthritis-linked loci.
      PVG.1AV1 alleles in the C4R1 recombinant did not affect arthritis, but conferred
      protection against MOG-EAE. PVG.1AV1 alleles in the C4R2 recombinant down
      regulated arthritis but had no effect in MOG-EAE. Paradoxically, PVG.1AV1 alleles
      in the C4R3 recombinant down-regulated arthritis, but the same fragment increased
      serum levels of anti-MOG Ab and aggravated clinical MOG-EAE. Thus, we provide
      original evidence that the same genome regions can have opposite effects in
      different organ-specific inflammatory diseases. Interestingly, no apparent
      difference in the MOG-EAE phenotype was observed in full-length congenic rats and
      parental DA rats, suggesting that the disease amelioration in C4R1 and
      aggravation in C4R3 functionally counteract each other. The data set the stage
      for definition of the mechanisms and positioning of the genes regulating two
      organ-specific inflammatory diseases differently.

PMID- 12811852
TI  - A feasibility study of the use of the AutoPap screening system as a primary
      screening and location-guided rescreening device.
AB  - BACKGROUND: The AutoPap 300 QC system (Tripath Imaging, Inc., Burlington, NC) is
      an automated device that was designed to screen conventionally prepared cervical
      smears and, more recently, thin-layer slide preparations. The system has been
      tested in large clinical trials. METHODS: A total of 14,145 cervical smears
      obtained from participants in the Florence screening program were eligible for
      the study. Smears were processed first with the AutoPap system and were
      classified into three different categories: 1) no further review (NFR), 2)
      review, and 3) process review (PR). Conventional manual reading was performed by
      10 experienced cytopathologists. RESULTS: After AutoPap processing, 2398 smears
      were classified as NFR (16.9%), and 1818 smears were classified as PR (12.8%).
      Overall, there were 188 inadequate smears (1.3%) at conventional review and 125
      inadequate smears (0.88%) at AutoPap review. Six-month repeat smears were
      prompted by 330 conventional reviews (2.3%) and by 222 AutoPap reviews (1.56%).
      Similarly, referral to colposcopy was prompted by 179 conventional reviews (1.2%)
      and by 147 AutoPap reviews (1.0%). Overall, 32 patients were diagnosed with high
      grade cervical intraepithelial neoplasia as a result of assessment. Conventional
      reading detected 31 patients (28 patients were referred for colposcopy, and 3
      patients were referred for repeat cytology), and the AutoPap system detected 30
      patients (27 patients were referred for colposcopy, and 3 patients were referred
      for repeat cytology). CONCLUSIONS: The current experience suggested that
      conventional reading and AutoPap reading of cervical smears had essentially the
      same sensitivity, with slightly greater specificity for the AutoPap system. Thus,
      comparisons of the AutoPap system and conventional reading should focus mainly on
      cost analysis.

PMID- 12811853
TI  - Cytohistologic correlation rates between conventional Papanicolaou smears and
      ThinPrep cervical cytology: a comparison.
AB  - BACKGROUND: The ThinPrep Papanicolaou (Pap) test, a liquid-based alternative to
      the long-used conventional Pap smear, received Food and Drug Administration
      approval in 1996. The current study is a comparison of the accuracy, as assessed
      by cytohistologic correlation, of conventional versus ThinPrep Pap smears in a
      hospital setting. METHODS: A retrospective analysis of all patients who underwent
      Pap smears (conventional and ThinPrep) and pertinent surgical pathology tissue
      processed in our department over a 1-year period was undertaken. Tissue diagnoses
      were grouped into broad general categories to correlate with the Bethesda system.
      The statistical significance of differences between the two types of Pap test
      results compared with tissue diagnoses was assessed using a chi-square test with
      1 degree of freedom and an alpha value of 0.05. RESULTS: Of the 65,421 Pap smears
      interpreted during the study period, histologic correlation was possible in 1544
      patients. Of those diagnosed as negative (644 conventional and 245 ThinPrep
      Smears), low-grade squamous intraepithelial lesion (LGSIL) (116 conventional and
      114 ThinPrep smears), and high-grade squamous intraepithelial lesions (HGSIL)
      (142 conventional and 131 ThinPrep smears), there was no statistically
      significant difference found between the correlation rates of conventional and
      ThinPrep Pap smear results. However, review of all cases of invasive cervical
      carcinoma identified during this time period showed the ThinPrep to be less
      consistent in predicting the presence of invasive carcinoma compared with the
      conventional Pap smear. CONCLUSIONS: Based on cytohistologic correlation
      evidence, the ThinPrep Pap test may not be more effective in detecting cervical
      disease, particularly invasive carcinoma, when compared with the conventional Pap
      smear.

PMID- 12811854
TI  - Significance of atypical repair in liquid-based gynecologic cytology: a follow-up
      study with molecular analysis for human papillomavirus.
AB  - BACKGROUND: "Atypical repair" is a controversial topic in gynecologic cytology.
      Although some cases do represent reparative change of dysplastic epithelium, the
      overall significance of identifying atypical reparative cells, especially in
      liquid-based cytology specimens, has not been investigated thoroughly. METHODS:
      All the liquid-based cytology cases with the diagnostic connotation of atypical
      repair were retrieved from the files of Pamela Youde Nethersole Eastern Hospital,
      Hong Kong, during a 4.5-year period from early 1998 to mid 2002. The clinical
      data and follow-up cytology/surgical biopsy findings were analyzed to explain the
      atypical cytologic change. Retrospective molecular analysis for human
      papillomavirus (HPV) using polymerase chain reaction and restriction fragment
      length polymorphism was also carried out on the liquid-based cytology samples.
      RESULTS: During the study period, the authors identified 21 patients with a
      cytologic diagnosis of atypical repair, for which follow-up information was
      available. The liquid-based cytology samples revealed scattered atypical squamoid
      cells demonstrating reparative change, including the presence of prominent
      nucleoli. In addition to typical repair, these cells showed more obvious nuclear
      pleomorphism, anisonucleosis, irregularities of nuclear outline, slight
      coarsening of the chromatin, and focal loss of nuclear polarity. Of the 21
      patients, 4 did not have a significant history of cervical/vaginal pathology
      before or after the cytologic examination, whereas the 17 remaining patients had
      squamous intraepithelial lesions (SIL; n = 9), genital prolapse (n = 3),
      endocervical polyps (n = 2), SIL/cervical carcinoma with local radiotherapy (n =
      2), or uterine malignancy with cervical extension (n = 1). These associations
      could not be delineated solely on the basis of morphologic assessment of the
      liquid-based cytology preparations. However, HPV DNA was detected frequently in
      cases of atypical repair associated with subsequent development of SIL (positive
      predictive value = 71.4%; negative predictive value = 77.8%). CONCLUSIONS: The
      presence of atypical reparative cells in liquid-based cytology is associated with
      a variety of conditions ranging from reactive to neoplastic conditions. Close
      follow-up with clinical correlation and further investigations (if indicated) are
      necessary for this group of high-risk patients. Reflex molecular analysis for HPV
      performed on liquid-based cytology samples is also helpful in predicting the
      possible association with an underlying SIL.

PMID- 12811855
TI  - Reflex human papillomavirus DNA testing on residual liquid-based (TPPT) cervical
      samples: focus on age-stratified clinical performance.
AB  - BACKGROUND: Liquid-based ThinPrep technology has made reflex human papillomavirus
      (HPV) DNA testing possible. In the current study, the clinical performance of
      reflex HPV testing as an adjunct to routine ThinPrep testing (TPPT) and the
      impact of age on various test parameters in a predominantly high-risk, minority
      population were evaluated retrospectively. METHODS: Reflex HPV testing was
      performed in 2114 women with atypical squamous cells of undetermined significance
      (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology, using
      probes for low-risk (LR) and high-risk (HR) HPV types. Six hundred thirty women
      underwent subsequent biopsies with which HPV testing results were correlated.
      RESULTS: Approximately 86% of the patients were Hispanic and African-American and
      12% were white. Of the younger women (ages 14-29 years), 81% were positive for HR
      types versus 50% in the older women (ages 30-77 years) (P < 0.0001). In women
      with ASCUS, 47% were found to be positive for HR types versus 78% of women with
      LSIL. The percentage of histologic high-grade lesions was 24% in younger patients
      versus 17% in older patients. Overall, 91% of high-grade lesions were positive
      for HPV DNA (HR-positive = 89% and LR-positive = 2%), and 9% were negative for
      both types. The sensitivities and specificities in "younger" versus "older" women
      were 92% (95% confidence interval [95% CI], 89-95%) and 22%% (95% CI, 17-26%),
      respectively, versus 84% (95% CI, 77-90%) and 59% (95% CI, 53-65%), respectively.
      CONCLUSIONS: The results of the current study demonstrate that reflex HPV testing
      performed in a routine clinical practice helps to identify the majority of women
      with high-grade disease. However, testing may be more beneficial in older women
      (age > or = 30 years) with ASCUS. Strategy using out-of-vial reflex testing is
      more cost-effective and sensitive than referring all women for colposcopies.

PMID- 12811856
TI  - Mammary lesions diagnosed as "papillary" by aspiration biopsy: 70 cases with
      follow-up.
AB  - BACKGROUND: The authors reviewed smears from fine-needle aspiration biopsies
      (FNAB) diagnosed as "papillary lesions" and correlated the cytologic findings
      with the final diagnoses at excision. The objective of the current study was to
      determine the accuracy of FNAB diagnosis of a papillary lesion in distinguishing
      true papillary from nonpapillary proliferations and to evaluate cytologic
      criteria for the distinction of papillomas from true papillary malignancies and
      their cytologic look-alikes. METHODS: The cytopathology database at the New York
      University Medical Center was searched for women who underwent surgical excision
      after a breast FNAB diagnosis of a papillary lesion. The FNAB smears and
      corresponding slides from excisional biopsies were reviewed. The smears were
      evaluated and graded for the following features: cellularity, architecture,
      presence of fibrovascular cores, single cells, columnar cells, cellular atypia,
      myoepithelial cells, foamy histiocytes, and apocrine cells. The F test was used
      to determine the statistical significance of differences between true benign
      papillary lesions (papilloma) and adenocarcinomas (in situ and invasive).
      RESULTS: At the time of excision, 46 (66 %) cases were benign (23 solitary
      intraductal papillomas, 6 intraductal papillomatosis, 11 examples of fibrocystic
      change, and 6 fibroadenomas) and 24 (34 %) were malignant (1 low-grade phyllodes
      tumor [PT], 23 ductal in situ and invasive carcinomas). Of the 23 carcinomas, 3
      (13 %) were classified as benign papillary lesions on FNAB and 19 (86 %) were
      classified as either atypical or suspicious. One case of low- grade PT originally
      was classified as benign on FNAB. There were four false-negative diagnoses; two
      were due to sampling and two to interpretative errors. A portion of the lesions
      classified as papillary were fibroadenomas and examples of fibrocystic change on
      excision and all of these were correctly classified as benign on FNAB. Of the
      histologically proven papillomas, 62% were correctly classified as benign on FNAB
      and none were designated as being positive for malignancy. Statistically
      significant features of distinction between papillomas and carcinomas included
      cellularity (P = 0.016), cellular atypia (P = 0.0053), and the presence of
      cytologically bland columnar cells (P = 0.04). Low-grade ductal carcinoma in situ
      (cribriform and micropapillary types) and tubular carcinoma represented the most
      difficult differential diagnostic problems. CONCLUSIONS: A significant portion of
      lesions displaying a papillary pattern on FNAB are nonpapillary on follow-up.
      Among benign processes, fibrocystic change and fibroadenoma may closely simulate
      papilloma on cytology. However, in spite of the overlapping features of true
      papillary lesions and their cytologic look-alikes, the majority can be classified
      accurately into benign or atypical (and above) categories by FNAB. Lesions that
      fall short of a definitive benign diagnosis should be placed into an
      indeterminate category. This approach will guide the surgeon to provide better
      patient management.

PMID- 12811857
TI  - Diagnostic accuracy and pitfalls in fine-needle aspiration interpretation of
      Warthin tumor.
AB  - BACKGROUND: Despite its well-defined histologic appearance, the often variegated
      cytomorphologic appearance of Warthin tumor (WT) on fine-needle aspiration (FNA)
      may lead to an erroneous cytopathologic interpretation. In this study, the
      authors analyzed the potential sources of diagnostic errors and overall accuracy
      of FNA diagnosis of WT. METHODS: A retrospective search of The Johns Hopkins
      Hospital Surgical Pathology files (1985-2001) revealed 97 patients with WT,
      including 31 patients who underwent prior FNA. A comprehensive review of
      cytopathologic material was undertaken to calculate the overall accuracy of FNA
      and to identify sources of diagnostic error. RESULTS: All tumors presented in the
      parotid gland. Four tumors (13%) were deemed inadequate for interpretation due to
      insufficient material. The FNA diagnosis of WT was rendered in only 20 tumors
      (74%). The remaining 7 tumors (26%) were misdiagnosed on FNA as consistent with
      or suspicious for carcinoma or some other neoplastic process. A retrospective
      review of the tumors, which were over-called on FNA, showed a predominance of
      necrotic or cellular debris (n = 6 tumors; 22%), significant epithelial
      metaplasia with atypia (n = 4 tumors; 15%), background inflammation suspicious
      for tumor diathesis (n = 3 tumors; 11%), spindle cells (n = 1 tumor; 4%), and
      abundant mucin with keratinized squamous cells (n = 1 tumor; 4%). CONCLUSIONS:
      FNA is moderately accurate for diagnosing WT, with a 74% accuracy rate in the
      current series. Cytologic misinterpretation may occur due to a lack of
      characteristic cytomorphologic features of WT and overabundance of one or more of
      the following: squamous metaplasia/atypia, mucoid/mucinous background, spindle
      shaped cells, and cystic/inflammatory debris. An adequate awareness of these
      potential sources of erroneous diagnoses, coupled with appropriate clinical
      findings, may result in a higher accuracy rate.

PMID- 12811858
TI  - Distribution of p63, a novel myoepithelial marker, in fine-needle aspiration
      biopsies of the breast: an analysis of 82 samples.
AB  - BACKGROUND: The presence of myoepithelial cells (MECs) in fine-needle aspiration
      biopsies (FNAB) of the breast constitute an important criterion used to diagnose
      benign breast lesions. However, MECs sometimes have a distorted cytomorphology,
      and most of the previously evaluated myoepithelial markers do not have
      satisfactory sensitivity and specificity. p63, a recently characterized p53
      homolog, is a nuclear transcription factor that is expressed in basal cells of
      multilayered epithelia and myoepithelial cells of the breast. The authors
      analyzed the immunocytochemical distribution of p63 in a series of 82 breast
      FNABs (30 benign lesions and 52 malignant breast lesions). METHODS: Eighty-two
      archival, Papanicolaou-stained smears of breast lesions were retrieved from the
      files of the authors' institutions. Immunocytochemistry was performed according
      to the streptavidin-biotin-peroxidase complex technique using the antibody 4A4
      (against all p63 isoforms). Two pathologists evaluated the distribution of p63
      positive cells. Only nuclear reactivity was considered specific. RESULTS: In
      benign lesions, p63 decorated the nuclei of MECs in all samples. p63 also stained
      naked nuclei in fibroadenomas. In malignant lesions, p63 was positive in MECs
      overlying malignant cell clusters in all 8 samples of ductal carcinoma in situ
      (DCIS), in 9 of 16 samples of pure invasive carcinomas (IC), and in 16 of 20
      samples that contained both DCIS and IC. In 18 samples (36%), a variable
      population of p63 positive, malignant cells was observed. p63 failed to decorate
      stromal, neural, adipocytic, and smooth muscle cells in all samples. CONCLUSIONS:
      p63 is a reliable nuclear marker of MECs in breast aspirates. Regardless of the
      fact that variable proportions of p63 positive, malignant cells were observed in
      36% of breast carcinoma aspirates, p63 may be a useful adjunct antibody to
      confirm the presence of MECs in FNABs of benign breast lesions.

PMID- 12811859
TI  - A single primer pair immunoglobulin polymerase chain reaction assay as a useful
      tool in fine-needle aspiration biopsy differential diagnosis of lymphoid
      malignancies.
AB  - BACKGROUND: Different polymerase chain reaction (PCR) assays have proved to be
      useful tools for the detection of clonal immunoglobulin heavy chain (IgH) gene
      rearrangements in frozen or paraffin-embedded tissues. However, the usefulness of
      a single primer pair PCR assay on fine-needle biopsy aspirates has not been
      proven yet. METHODS: The authors conducted a wide prospective study of 148 lymph
      nodes and extranodal lymphoid infiltrates obtained by fine-needle aspiration
      biopsy (FNAB). The power of a single primer pair PCR amplification of the
      hypervariable CDRIII region IgH genes was evaluated using a pair of consensus
      primers. The PCR cytologic results were compared with the final clinicopathologic
      diagnosis of each case assessed by combining cytologic and/or immunophenotypic
      data and histologic features or clinical follow-up. RESULTS: Among the 139 cases
      with an evaluable PCR result, 35 of 40 (87%) B-cell non-Hodgkin lymphomas were
      detected as a monoclonal band. Monoclonal IgH bands also were detected in two of
      the five (40%) T-cell lymphomas, two of the seven (29%) Hodgkin lymphomas, and 5
      of the 87 (6%) reactive lymphoid disorders. These results are similar to those
      obtained by other authors using seminested PCR or combining different PCR tests
      in each sample obtained by FNAB or excisional biopsy. CONCLUSIONS: The results of
      the current study demonstrate the convenience of a single primer pair PCR
      amplification over seminested methods in terms of lower cost and workload. The
      existence of PCR false-negative and false-positive results for lymphoma makes it
      necessary to combine the information obtained by PCR with cytologic and/or
      immunophenotypic data to optimize the number of lymphoid malignancies correctly
      diagnosed by FNAB.

PMID- 12811860
TI  - Thrombolysis in peripheral general practices in Scotland: another rule of halves.
AB  - OBJECTIVE: To facilitate the adoption of thrombolysis by general practitioners in
      peripheral practices in Scotland. DESIGN: Survey of practice policies on the
      management of acute myocardial infarction before and after practice visits by a
      consultant physician acting as a facilitator; survey of hospital consultants'
      attitudes to thrombolysis by general practitioners. SETTING: One hundred and
      eighty-two practices, with an enlisted total of 550,000 patients, located at
      least 30 minutes from a district general hospital; 23 such hospitals serving
      these peripheral practices. MAIN OUTCOME MEASURES: Possession of
      electrocardiograph and defibrillator; adoption of a policy of giving thrombolytic
      therapy. RESULTS: The majority of practices possessed an electrocardiograph (87%)
      and a defibrillator (76%). At the time of the visits, 67 practices (37%) already
      had a policy of giving thrombolytic therapy. When contacted one year later 91
      practices (50%) had such a policy. In the interval between visits and follow-up,
      few had received any encouragement from any source to use this treatment.
      Hospital consultants' attitudes to thrombolysis by general practitioners were
      generally negative, and support from local and national health authorities has
      been inadequate. CONCLUSIONS: Provision of timely thrombolytic therapy for the
      one tenth of the Scottish population living at least 30 minutes from a district
      general hospital is a major public health problem for which there is a ready
      solution: pre-hospital thrombolysis administered by general practitioners has
      been shown to be feasible, fast, safe, efficacious and cost-effective. To
      translate this evidence into practice requires a concerted effort from all the
      professionals involved, and must be directed and supported by local and national
      management of the National Health Service in Scotland.

PMID- 12811861
TI  - Analysis of six months' referrals to a "one-stop" neurovascular clinic in a
      district general hospital: implications for purchasers of a stroke service.
AB  - OBJECTIVE: To determine the effectiveness of a "one-stop" neurovascular clinic
      (NVC) in guiding the diagnosis and investigation of patients suffering a mild
      stroke or transient ischaemic attack (TIA). DESIGN: Six months' survey of the
      activity of a new neurovascular clinic (NVC). SETTING: Borders region of
      Scotland. SUBJECTS: Patients referred with a suspected diagnosis of stroke or
      TIA. RESULTS: The clinic served 23 general practices and a population of 106,000.
      Over a 6 month period 128 patients were referred; 93% of patients were referred
      by general practitioners, 5% by consultant physicians and 2% from wards in the
      Borders General Hospital. Most patients were independent prior to the presenting
      event and had minimal disability on presentation to the clinic. Patients were
      seen within 48 hours of referral in the majority of cases and all within five
      working days. However, only 52% were seen within two weeks of the onset of their
      symptoms. Only 50% of patients were shown to have sustained a stroke or TIA. A
      variety of other diagnoses mimicked vascular events including epilepsy, migraine,
      cranial nerve palsies and cerebral tumour. The stroke-related group differed
      significantly in age (P = 0.003) and in the number of patients already on aspirin
      (P = 0.010) but not in any other risk factor. CT scan and carotid doppler
      examination were considered necessary in only 47% and 24% respectively of
      referred patients. Only five stroke-related patients and one non-stroke-related
      patient needed further input from physiotherapy, occupational therapy or speech
      therapy. Over 90% of patients were discharged home. Patient and general
      practitioner satisfaction with the service received were rated at 9 (0 = very
      poor; 10 = excellent). CONCLUSION: Applying evidence-based medicine to patients
      attending a "one-stop" neurovascular clinic with minor stroke and/or transient
      ischaemic attack resulted in an efficient delivery of appropriate investigations
      and therapy to this group of patients. The NVC prevented unnecessary requests for
      both CT scanning and carotid doppler examination, which are valuable resources,
      and may have prevented admissions to hospital. Patients were anxious about their
      symptoms and appreciated being seen quickly and a diagnosis made. We would
      recommend that these clinics be set up as part of the stroke service in all
      district general hospitals.

PMID- 12811862
TI  - Use of collaborative audit to assist local implementation of the SIGN guideline
      for prevention of visual impairment in diabetes.
AB  - OBJECTIVES: To use audit to inform the local implementation of a national
      clinical guideline for the prevention of visual impairment in diabetes. DESIGN:
      Computer and patient record search in hospital and general practice to determine
      levels of morbidity and follow-up. Questionnaire to each practice to determine
      models and techniques of eye screening. SETTING: Ayrshire and Arran Health Board
      area, Scotland. SUBJECTS: All known diabetic patients. MAIN MEASURES: Proportion
      of diabetic patients who have had diabetic eye review and monitoring of risk
      factors within one year. Proportion of diabetic patients who have risk factors
      recorded within target level. Proportion of eye screening centres with
      recommended mechanisms in place. RESULTS: Both district general hospitals, and 59
      of the 63 general practices, in the area took part in the audit. A total of 6,217
      diabetic patients were included; the prevalence of diabetes in this population
      was 1.65%. Twenty-seven per cent were insulin treated. Seventy-two per cent of
      diabetics who were not registered blind had a record of having had fundoscopy
      performed through dilated pupils within one year. Sixty-nine per cent of those
      who were not registered blind had had corrected visual acuity measured within one
      year. Eighty-five per cent of diabetics had HbA1C recorded within one year and of
      these 65% had a level of 8% or less. Eighty-eight per cent had a blood pressure
      recording within twelve months and 52% of recorded pressures were 140/90 mmHg or
      less. Smoking status was recorded for 89% of patients and 75% of patients with a
      record were non-smokers. Representatives of 57 practices returned a completed
      questionnaire. All these practices had a Snellen chart, but only 83% had near
      vision testing equipment and only 54% had a pinhole occluder. CONCLUSIONS: An
      area wide collaborative audit provided local data to inform the process of
      guideline implementation and baseline data from which to evaluate this process.
      Wide stakeholder involvement increased interest, motivation and support for the
      process. The audit highlighted specific areas for change and provided the local
      stimulus for change.

PMID- 12811863
TI  - General practitioners' and nurses' perceived roles, attitudes and stressors in
      the management of people with dementia.
AB  - BACKGROUND: GPs and nurses play a major role in dementia care. Negative attitudes
      and uncertainties may be common sources of stress in both professions. Specific
      anxieties related to dementia management in primary care need to be identified.
      AIM: To assess whether dementia care is a stress-provoking experience and examine
      perceived roles, attitudes, and anxieties for GPs and nurses working with people
      with dementia and their informal family carers. DESIGN: A structured self-report
      questionnaire administered opportunistically to GPs and nurses attending dementia
      education seminars. RESULTS: 298 doctors and 487 nurses participated (response
      rate 98%). Over half dealing with people with dementia and their carers
      stressful. GPs reported more negative attitudes to dementia care than nurses (p <
      0.001), and felt that professionally they could offer less to people with
      dementia (p < 0.001) and carers (p < 0.05) than nurses, reporting more
      difficulties with aspects of dementia care. For GPs and nurses, factors outwith
      their own profession's 'traditional' role were more stressful, e.g. responding to
      patients' behavioural (p < 0.001) and social problems (p < 0.001) were stressful
      for a greater proportion of GPs than nurses. Responding to patients' psychiatric
      problems was more stressful for nurses than GPs (p < 0.05). More GPs than in
      previous studies reported routinely administering tests of memory (70%) and
      depression (58%) in diagnosis. CONCLUSION: Negative attitudes towards dementia
      care are associated with increased stress for GPs and nurses. Difficulties and
      uncertainties in these professional roles should be addressed by education in
      dementia management and improved awareness of available services and resources
      for people with dementia and their carers.

PMID- 12811864
TI  - Characteristics and career intentions of Scottish rural and urban GP registrars:
      cause for concern?
AB  - OBJECTIVES: To investigate the differences between the characteristics and career
      intentions of GP registrars in urban and rural areas, and to make recommendations
      to reduce a potential work force crisis in rural practice. DESIGN: Postal survey.
      SETTING: All general practices in Scotland. SUBJECTS: In February 1996, 40/196
      (20%) of urban and 45/150 (30%) of rural GP registrar places available in
      Scotland, were vacant (chi 2 = 4.22, df = 1, p = 0.02). Postal questionnaires
      were sent to all 261 GP registrars in post. RESULTS: Of 235 respondents (90%),
      the majority wished to remain in general practice (63% of urban and 53% of rural
      registrars), but only 22% of urban and 18% of rural registrars intended to apply
      for principal posts immediately after training. Fewer urban (8%) than rural
      registrars (21%) stated an intention to go abroad to work after training. Rural
      registrars tended to want to work in rural areas, and vice versa. Part-time and
      job-sharing were attractive employment options for both groups, and more flexible
      career structures were favoured by over 80%. CONCLUSIONS: Though much more
      attention has been paid to recruitment in inner cities, the findings from this
      study suggest that in Scotland difficulties in finding principals may occur first
      in rural areas. As general practitioners have an extended role in rural areas,
      including that of emergency care, shortages could have a serious impact on
      patient care.

PMID- 12811865
TI  - Grading of scientific evidence--a discussion paper from SHPIC.
AB  - This paper examines some of the issues in the grading and use of evidence, and
      suggests that the (US) Agency for Health Care Policy and Research (AHCPR) system
      used by the Scottish Intercollegiate Guidelines Network (SIGN) and others is
      useful, but that it needs development to take account not only of type of study,
      but also of quality. It also considers the need to complement evidence of
      efficacy from randomised controlled trials, which may involve selected patients
      in selected centres, with evidence of "real-life" effectiveness. Furthermore,
      there are occasions where randomised controlled trials are not necessary. A
      grading system to take account of these issues is proposed for discussion.

PMID- 12811866
TI  - The Framework for Mental Health Services in Scotland--a progress report one year
      on.
AB  - Progress in implementing the Framework for Mental Health Services in Scotland
      since its launch in September 1997 is described. Reasons for action being behind
      the expected timetable are discussed. The success of the joint strategies, due
      for completion by the end of December 1998, hinges on overcoming the deep
      systemic factors which mitigate against change. The Framework as a template has
      the potential to be a powerful change agent to counter these. The development of
      better services requires a balance of "top down" and "bottom up" approaches, and
      front line staff must be actively engaged in the process.

PMID- 12811867
TI  - Linking Community Health Index and Scottish Morbidity Records for neonates: the
      Grampian experience.
AB  - OBJECTIVE: To describe linking Community Health Index (CHI) records with Scottish
      Morbidity Records for neonates (SMR11) for the purpose of follow-up in a large
      clinical trial. DESIGN: A two-stage probabilistic computer match based on date of
      birth, surname and postcode, supplemented with hand matching. SETTING: Aberdeen
      Maternity Hospital, Grampian. SUBJECTS: 10,835 babies born in the two year period
      between 1 March 1993 and 28 February 1995. RESULTS: The computerised linkage
      matched 89.8% of the SMR11 records to a CHI record. All of the remaining 10.2%
      unlinked babies were accounted for by manual checking. There were 194 (1.8%)
      babies who did not have a CHI record due to the baby leaving the area or dying
      before allocation was possible. The sensitivity of the matching was estimated at
      99.9% (95% CI is 99.8% to 100%). CONCLUSION: We were able to correctly computer
      match 89.7% of our babies' SMR11 records with the appropriate CHI number. We have
      shown that the follow-up of neonates in a clinical trial setting using record
      linkage between secondary and primary care systems is feasible, efficient and
      useful. However, this exercise would have been greatly facilitated by a unique
      NHS identifier common to all records.

PMID- 12811868
TI  - Inflammatory bowel disease in Scottish children.
AB  - Most children with inflammatory bowel disease (IBD) require specialist care in a
      tertiary medical centre. The records of 105 children with IBD who presented to
      the Royal Hospital for Sick Children, Glasgow between 1976 and 1995 were studied
      retrospectively. Fifty seven children and Crohn's disease (CD) (median age of
      presentation 7.9 years) and 48 had ulcerative colitis (UC) (median age of
      presentation 8.7 years). The number with CD doubled in the decade 1986-95
      compared to 1975-85. 23% with CD and 13% with UC developed symptoms before the
      age of five years. Median time to diagnosis from symptom onset was 45.8 weeks for
      CD and 12.7 weeks for UC. Histological diagnosis was obtained in all children.
      The mainstay of treatment was aminosalicylates, and few children underwent
      surgery (CD 26%, UC 10%). Thirty percent with CD and 23% with UC had no relapses
      in the study period, and only one child with UC died. Growth was poorly recorded.
      The majority of children with CD and over 50% with UC had a height-for-age Z
      score below zero.

PMID- 12811869
TI  - Audit of the nutritional content of patient meals in Ayrshire and Arran.
AB  - Recent studies have indicated an unacceptably high prevalence of malnutrition in
      hospital patients and inadequacies in the diets offered to patients. In 1995 the
      Health of the Nation Nutrition Guidelines for Hospital Catering were produced
      with the aim of raising standards in hospital catering. An audit was conducted to
      compare the nutritional adequacy of patient meals provided by three NHS Trusts
      within Ayrshire, with the Health of the Nation Guidelines. Across the three
      Trusts approximately 45% of days failed to provide the recommended minimum amount
      of energy. NSP, folate and vitamin C provision was adequate in all three Trusts.
      However there were some inadequacies in the provision of calcium, iron and zinc.
      In two of the Trusts approximately, half, and in the other Trust one third, of
      the main meals failed to provide the recommended 300 kcals. In all three Trusts
      approximately one third of vegetarian meals failed to provide the recommended
      amount of protein. It has been recommended that the current menus in the three
      Trusts are altered to ensure that the nutritional standards in the Guidelines are
      met. Additionally a menu coding system, which indicates the suitability of dishes
      for different diets, should be used. The three Trusts have agreed to collaborate
      to produce a core set of menus that meet the recommendations. These
      recommendations will be implemented along with those from the National Food and
      Health Best Practice Guide.

PMID- 12811870
TI  - Early-onset dementia in Lothian, Scotland: an analysis of clinical features and
      patterns of decline.
AB  - OBJECTIVE: To clinically characterise and diagnostically classify a sample of
      patients with early-onset dementia and determine the disabilities and nature of
      decline of each group, during a one year follow up. DESIGN: The Lothian
      Postgraduate Case Register was used to identify a cohort of 126 live patients of
      various aetiologies with dementia diagnosed before the age of 65. Each had two
      assessments approximately one year apart. Demographic; behavioural and
      psychopathological; neurocognitive; neurological and genetic data were collected
      and compared. SETTING: Patients were either in long term care or at home.
      SUBJECTS: Of 126 cases (53 male, 73 female, mean age at referral 58 years), 114
      met the diagnostic criteria for Diagnostic and Statistical Manual Third Edition
      dementia; 60 Alzheimer's type Dementia; 13 Multi-infarct Dementia; 14 Alcohol
      related Dementia; with 25 in a mixed group overlapping these categories; and two
      in 'other' dementia types. By the second assessment, 18 patients had died and two
      refused reassessment. RESULTS: Levels of morbidity were high. The Alcohol group
      had a distinct profile and in general the dementia appeared less severe with
      minimal deterioration. CONCLUSIONS: This study investigates and compares early
      onset dementia of various types and attempts to provide clear information on
      their outlook.

PMID- 12811871
TI  - A survey of factors affecting the recruitment and retention of Medical Laboratory
      Scientific Officers in Pathology.
AB  - OBJECTIVE: To survey the perceptions and attitudes of Medical Laboratory
      Scientific Officer (MLSO) staff in Pathology to explain difficulties in
      recruitment and retention and inform attempts to solve the difficulties. DESIGN:
      Questionnaire to a defined group of MLSOs. SETTING: The Laboratory Medicine
      Directorate, Aberdeen Royal Infirmary. SUBJECTS: MLSO1 and MLSO2 staff currently
      or recently working in Pathology (histopathology) in Aberdeen. RESULTS: The
      survey return rate was 100%. Opportunities for career development in Pathology
      are poor, this being the worst feature of working in Pathology. Remuneration is
      poor and is a disincentive to remaining in the speciality. MLSOs feel undervalued
      in relation to other health care workers. Many have concerns about laboratory
      organisation, but find a sociable and supportive environment that provides job
      satisfaction. Staff seek work in other laboratories because of opportunities for
      promotion, learning new skills and increased pay, although pay in specialities
      other that Pathology is greater only because of shift working in these
      disciplines. There is a need to increase public awareness of MLSOs' central role
      in providing and maintaining excellence in Pathology services. CONCLUSION: MLSO
      staff have concerns about their career structure and salary scales. The
      responsibility of MSLOs in Pathology for quality assurance and managing MLAs is
      not recognised. These factors form a disincentive to working in Pathology
      laboratories and threaten our ability to staff the service and to maintain the
      turnover and quality of Pathology services. These issues require to be addressed
      nationally and rapidly to prevent the continuing decline in MLSO numbers. Matters
      of local organisation might be addressed by trusts and departments, but
      recognition of the need to resource changes would require reflection in budgets.

PMID- 12811872
TI  - The detection of childhood deafness in Ayrshire.
AB  - OBJECTIVE: To determine the age at referral and at first fitting of hearing aids
      for children with a bilateral sensorineural hearing impairment of 30dB or more
      born in Ayrshire 1991-1996. To assess the value of routine health visitor
      distraction test screening for hearing impairment. To identify areas for
      improvement in the service. DESIGN: A review of data contained within the
      prospectively collected. Educational Audiology database. SETTING: Area covered by
      the Ayrshire and Arran Health Board. SUBJECTS: Children born in the years 1991
      1996 who were screened for hearing impairment by the distraction test, and those
      born in the same period who have been identified as having a bilateral
      sensorineural hearing impairment of 30dB or worse. RESULTS: Thirty-two hearing
      impaired children were identified from the database. The distraction test screen
      had a sensitivity of 45%, a specificity of 93%, a positive predictive value of
      0.6% and a negative predictive value of 99.9%. Forty eight percent of hearing
      impaired children were diagnosed before the age of one year, and 17% before six
      months. Sources of delay were identified at all stages of the process from
      initial identification to fitting of hearing aids. CONCLUSION: There remain scope
      for improvement in the detection of hearing impairment in Ayrshire.

PMID- 12811873
TI  - Medical and dental staffing in the health service in Scotland in 1998.

PMID- 12811874
TI  - The Westdoc Internet Questionnaire--a survey of the use of "on-line" resources by
      West Lothian general practitioners.
AB  - OBJECTIVE: To investigate the extent to which a representative sample of Scottish
      GPs used on-line resources for medical applications and their attitudes to
      various aspects of the technology at a time just prior to the introduction of the
      Scottish Office Computers offering Internet access to the majority of Scottish
      practices. DESIGN: Questionnaire survey. SETTING: "Out of hours" GP emergency
      service cooperative. SUBJECTS: All the (106) GP principals in practice in the
      Scottish District of West Lothian in June 1997. Locums and Registrars were
      excluded. RESULTS: There was an 87% response rate. Nineteen (21%) respondents
      used the Internet once a month or more, 12(13%) used it to communicate with
      colleagues by e-mail and 4(4%) with patients. Only 8% found it useful for medical
      purposes though more than half thought it would be a significant part of practice
      in five years time. Younger GPs were more likely to use the Internet. Many users
      expressed concern about reliability of the information and the ease with which it
      could be applied. CONCLUSION: By identifying a mismatch between levels of
      Internet use and the perceived potential of this new technology this study points
      to the need for training initiatives. It also forms a benchmark against which the
      uptake of Internet technology by GPs can be measured in years to come.

PMID- 12811875
TI  - Low incidence of asymptomatic deep venous thrombosis following caesarean section:
      a colour Doppler study.
AB  - OBJECTIVE: To determine the incidence of puerperal asymptomatic deep venous
      thrombosis (DVT) amongst women undergoing Caesarean section. DESIGN: Prospective
      observational study. SETTING: Ninewells Hospital, Dundee. SUBJECTS: One hundred
      and twenty-nine women delivered by Caesarean section underwent lower limb colour
      Doppler imaging (CDI) between days two and five postpartum. RESULTS: No cases of
      DVT were detected using CDI. During the study, there was one case of confirmed
      pulmonary embolism in the early puerperium with no evidence of persisting
      thrombosis. CONCLUSION: The incidence of asymptomatic DVT post-Caesarean section
      is very low and appears to be lower than that previously described using
      nonultrasound methods of detection. This information should be useful for those
      wishing to design guidelines of thromboprophylaxis for this population.

PMID- 12811876
TI  - A self-report outcome measure for the evaluation of hearing aid fittings and
      services.
AB  - OBJECTIVE: To design, optimise and validate an outcome measure for the evaluation
      of adult hearing aid fittings. DESIGN: A multi-dimensional subject-specific and
      situation-specific questionnaire (the Glasgow Hearing Aid Benefit Profile--GHABP)
      to assess initial disability, handicap, use, benefit, residual disability and
      satisfaction before and after hearing aid provision. SUBJECTS: Hearing-impaired
      adults attending National Health Service clinics for the first time for whom
      amplification is an appropriate management option. RESULTS: A self-report
      instrument of length compatible with the requirements of routine clinical
      practice which retains psychometric leverage. The GHABP demonstrates sensitivity
      to the technological content and rehabilitative context of interventions. The
      scale properties facilitate the use of the GHABP in decision-making for
      individual hearing-impaired patients. CONCLUSION: An outcome measure such as the
      GHABP offers the various interested parties (purchasers, providers and patients)
      a tool for use in the evaluation of the effectiveness and cost effectiveness of
      existing services and future developments. Many of the design concepts embodied
      in the GHABP are applicable in other healthcare contexts.

PMID- 12811877
TI  - Shaping the future: a primary care research and development strategy for
      Scotland.
AB  - Primary care is at the centre of the National Health Service (NHS) in Scotland;
      however, its R & D capacity is insufficiently developed. R&D is a potentially
      powerful way of improving the health and well-being of the population, and of
      securing high quality care for those who need it. In order to achieve this, any
      Scottish strategy for primary care R&D should aim to develop both a knowledge
      based service and a research culture in primary care. In this way, decisions will
      be made based upon best available evidence, whatever the context. Building on
      existing practice and resources within primary care research, this strategy for
      achieving a thriving research culture in Scottish primary care has three key
      components: A Scottish School of Primary Care which will stimulate and co
      ordinate a cohesive programme of research and training. A comprehensive system of
      funding for training and career development which will ensure access to a range
      of research training which will ensure that Scotland secures effective leadership
      for its primary care R&D. Designated research and development practices (DRDPs)
      which will build on the work of existing research practices, in the context of
      Local Health Care Co-operatives (LHCCs) and Primary Care Trusts (PCTs), to create
      a co-operative environment in which a range of primary care professionals can
      work together to improve their personal and teams' research skills, and to
      support research development in their areas. A modest investment will create
      substantial increases in both the quality and quantity of research being
      undertaken in primary care. This investment should be targeted at both existing
      primary care professionals working in service settings in primary care, LHCCs and
      PCTs, and at centres of excellence (including University departments). A dual
      approach will foster collaboration and will allow existing centres of excellence
      both to undertake more primary care research and to support the development of
      service based primary care professionals in their research. Resources should be
      distributed equitably, taking into account demography, geography and the health
      needs of patients in Scotland. The strategy and its components must be seen as a
      whole. The Scottish School of Primary Care will stimulate and co-ordinate both
      research and training programmes. DRDPs will become research active and will
      participate in School-led training and research, and will contribute to research
      programmes. Comprehensive funding for training and career development will ensure
      that staff have the skills to participate in both DRDPs and in the School's
      activities. Thus, inadequate commitment to any one component of the strategy will
      mean that other components will be less successful. Commitment to all three
      components will maximise the chances of success.

PMID- 12811878
TI  - Changes in the pattern of work in a rural community hospital 1987-1997.
AB  - OBJECTIVES: To examine time trends in clinical activity at a rural community
      hospital, and to assess associated changes in the complexity of the care received
      by inpatients. DESIGN: Descriptive study utilising routine Scottish Morbidity
      Records data (SMRO1) and locally collected data, along with a retrospective
      review of admission case notes to quantify clinical inputs to patient care.
      SETTING: Portree community hospital on the island of Skye. SUBJECTS: Patients
      admitted to Portree community hospital in 1987, 1992 and 1997. RESULTS: We found
      an 80 per cent rise in total annual admissions between 1987 and 1997 and a 34 per
      cent rise in annual casualty attendance between 1992 and 1997. There was a
      significant reduction in the median duration of in-patient stay, from 8.5 days in
      1987 to 6.0 days in 1997. The case-mix of admissions altered significantly
      between 1992 and 1997. We also demonstrated significant changes in the proportion
      of patients receiving blood transfusions or intravenous (i.v.) fluids during this
      time period. CONCLUSIONS: There have been significant changes in the pattern of
      use of this community hospital over the past 12 years. The rise in total
      admissions and casualty attendances, combined with the fall in duration of stay
      reveal an overall increase in activity at the hospital. This has been associated
      with changes in the clinical spectrum of admissions. Taken together with the
      results of the workload analysis, it seems likely that the complexity of the
      clinical input required at the hospital has increased, and that the role of this
      community hospital is increasingly the provision of intermediate care to acute
      cases.

PMID- 12811879
TI  - The epidemiology of lung cancer in Scotland: a review of trends in incidence,
      survival and mortality and prospects for prevention.
AB  - OBJECTIVE: The aims of the study were to review long-term trends in lung cancer
      incidence, survival and mortality and, in light of these, to consider prospects
      for prevention. DESIGN: Descriptive epidemiological study. SETTING: Scotland.
      SUBJECTS: Incident cases of lung cancer, diagnosed 1959-1993, and registered with
      the Scottish Cancer Registry, and recorded deaths from lung cancer during 1919 to
      1993. RESULTS: Scottish men and women continue to experience rates of lung cancer
      which are amongst the highest in the world. In men, incidence rose from 1959 to a
      peak in the late 1970s and is now decreasing steadily. In women, although
      starting from a lower baseline, incidence has risen steadily since 1959 (at an
      annual rate of increase of 5.0 per cent) and shows no evidence of a sustained
      decline. It is estimated that, between 1986 and 2000, the annual number of
      registrations in those aged under 85 years could fall by 20 per cent in men and
      rise by 8 per cent in women. Incidence in the most deprived areas of Scotland is
      twice that in the least deprived areas. Survival prospects have changed little
      over the last 25 years. In both sexes, trends in mortality mirror trends in
      incidence. CONCLUSION: Although lung cancer incidence in men is falling, it is
      likely that we have not yet reached the peak of the lung cancer epidemic amongst
      women. As up to 90 per cent of these tumours are attributable to tobacco,
      measures to control this drug should be the main focus of prevention activities.
      Emphasis should be placed on efforts to cut smoking prevalence among women and
      the most deprived groups of society and to reduce the uptake of smoking amongst
      the young. The fact that some other countries report more favourable survival
      figures suggests that there may be scope for improvements in diagnosis and
      therapy. The formulation of guidelines for best current practice in the
      management of lung cancer should aid progress in this respect.

PMID- 12811881
TI  - Using audit to monitor and improve the quality of anaesthesia for caesarean
      section.
AB  - OBJECTIVE: To improve the quality of anaesthesia for caesarean section by
      assessing the type and reason for using a particular anaesthetic; monitoring the
      incidence of anaesthetic complications or side effects; and measuring patient
      satisfaction with anaesthesia provided. DESIGN: Repeat audit undertaken
      retrospectively using a pre-designed database developed on EPI info public domain
      software. SETTING: Maternity unit of a district general hospital. SUBJECTS: 166
      women undergoing emergency or elective caesarean section. RESULTS: An initial
      audit involving 79 patients undergoing emergency and elective caesarean section
      revealed the following: 58.0 per cent of emergency sections and 45.5 per cent of
      elective sections were given general anaesthesia; "failure to progress" was
      indicated as the main reason for caesarean section in 27.8 per cent of cases;
      25.3 per cent of patients experienced an anaesthetic-related complication or side
      effect; and 90.3 per cent of patients were satisfied with their anaesthesia
      rising to 97.2 per cent after technical adjustment. The main findings were
      presented to the multi-disciplinary team staffing the unit. It was agreed that
      the quality of care could be further improved and changes to anaesthetic practice
      were quickly introduced. A subsequent re-audit of a further 87 patients showed a
      number of significant improvements: the overall use of general anaesthesia had
      fallen to 23.8 per cent from 53.0 per cent (P < 0.05); a noticeable reduction in
      the number of anaesthetic side-effects and complications had occurred, down from
      25.3 per cent to 17.2 per cent of all sections; and patient satisfaction rates
      with anaesthesia provided were maintained.

PMID- 12811880
TI  - Out-patient and home-parenteral antibiotic therapy (OHPAT): evaluation of the
      impact of one year's experience in Tayside.
AB  - OBJECTIVE: An out-patient and home parenteral antibiotic therapy programme for
      the treatment of suitable infections was developed over a four year period. This
      paper describes the impact of one year's experience of its implementation on
      various measures of outcome. DESIGN: Each patient treatment has a full integrated
      care pathway (ICP) and patient satisfaction questionnaire completed. The ICP
      documents the clinical progress of the patient and incorporates various measures
      of quality of care on the 101 number of patients treated from April 1998 to March
      1999 are presented here. SETTING: Dundee Teaching Hospitals NHS Trust (now
      Tayside University Hospitals NHS Trust). SUBJECTS: Patients with a range of
      infections requiring intravenous antibiotics. MAIN MEASURES: Number of patients
      treated with various infections, clinical and microbiological outcome, drug and
      vascular access complication rates, impact on drug costs and in-patient bed days,
      and measurement of patient satisfaction/quality of life. RESULTS: Patients were
      treated over a 12 month period. 51.5 per cent had skin & soft tissue infections
      and 22.8 per cent bone & joint sepsis. 57 per cent of patients received out
      patient and 34 per cent self or carer administered home therapy. Ninety-four per
      cent of patients were cured or improved following treatment. Only 7.5 per cent of
      patients required an unscheduled admission to hospital. Twelve per cent of
      patients had some type of vascular device related adverse event (partly due to a
      faulty batch of lines) and six per cent of patients had a drug related reaction.
      The additional daily cost of drugs was minimal (< 12 Pounds/day) and more than
      1,461 bed days have been saved across the Directorates. The patient satisfaction
      level was high.

PMID- 12811882
TI  - GP non-principals in north-east Scotland--a valuable pool of medical labour or
      second-class citizens? Results of a questionnaire survey.
AB  - OBJECTIVES: (1) To identify all general practitioner [GP] non-principals in the
      Grampian Health Board area (north-east Scotland), (2) To seek their views via a
      questionnaire survey, (3) to offer them the opportunity to meet individually with
      an Associate Adviser [GP Tutor]. DESIGN: All GP practices were contacted,
      requesting the names of non-principals. A questionnaire was sent, where possible,
      to all non-principals so identified. SETTING: The Grampian Health Board area in
      north-east Scotland. SUBJECTS: One hundred and nine names were obtained, 90
      questionnaires were mailed and a final response rate of 67 per cent was achieved.
      RESULTS: Eighty-seven per cent of respondents were female (median age--35 years);
      92 per cent were vocationally trained; 89 per cent had at least one postgraduate
      qualification; 32 per cent had been a principal; 68 per cent agreed to meet with
      an Associate Adviser. There was considerable confusion regarding entitlement to
      funding for continuing medical education [CME]. Advantages of working as a non
      principal included the flexibility of working part-time and limited involvement
      in practice administration and out-of-hours work. However, many disliked their
      inferior conditions of employment, their inability to follow up patients and the
      negative attitudes displayed by some principals. Feelings of professional
      isolation, lack of involvement in practice decision-making and employment
      insecurity were also cited as disadvantages. Short-term career plans included
      maintaining the status quo (45 per cent); increasing work commitment (26 per
      cent) or becoming a principal (11 per cent), while in the longer term, 67 per
      cent of those intending to remain in general practice wished to do so on a part
      time basis. The main factors determining career plans were family commitments
      and/or availability of suitable posts. CONCLUSIONS: Demand for part-time
      principal posts will undoubtedly increase. Regional databases of non-principals
      must be established and all GPs must have equal access to CME particularly in the
      light of the General Medical Council's [GMC] pronouncements on revalidation of
      all doctors.

PMID- 12811883
TI  - Childhood injury mortality in Scotland, 1981-95.
AB  - OBJECTIVE: To examine the trends in childhood injury mortality in Scotland
      between 1981 and 1995. DESIGN: Analysis of mortality data from the Registrar
      General for Scotland. SETTING: Scotland, UK. SUBJECTS: Children aged 0-14 years.
      MAIN RESULTS: A total of 1,728 children died in Scotland as a result of an injury
      between 1981-1995. While a significant decrease in the rates of unintentional
      injury mortality was observed for both sexes, all ages and most causes over the
      study period, the proportion of total child deaths due to injury decreased only
      slightly. Road traffic accidents were the major cause of injury mortality in this
      age group, representing over 40% of all injury deaths both at the beginning and
      the end of the study period. Males and young children of both sexes had
      consistently higher injury mortality rates. Similar reductions in injury
      mortality rates were observed for males and females. CONCLUSIONS: Childhood
      injury mortality rates have declined in Scotland, affecting all injury causes.
      The analysis of injury mortality rates in the population is helpful in
      highlighting potential environmental hazards that result in injury and in
      monitoring progress towards the achievement of national and local targets.

PMID- 12811884
TI  - Neonatal abstinence syndrome at Glasgow Royal maternity hospital.
AB  - OBJECTIVE: To get a clearer idea of the magnitude of the problem of Neonatal
      Abstinence Syndrome and, in particular, the number of cases and the severity and
      length of any withdrawal symptoms. DESIGN: Retrospective review of casenotes.
      SETTING: GRMH, Rottenrow Neonatal Unit Jan 1994-Aug. 1996. SUBJECTS: Infants
      admitted to the Neonatal Unit with the label "Infant of a Drug Abusing Mother"
      and their mothers. RESULTS: Sixty-four infants qualified for the audit i.e. on
      average two children per month. Most mothers had a polydrug habit taking both
      opiates and benzodiazepines. Thirty per cent of infants were premature and, as a
      group they were lighter and had a smaller OFC than the national average. Fifty
      three infants suffered NEONATAL ABSTINENCE SYNDROME, 50 of these being "jittery,
      restless or irritable". Only four had convulsions. Most infants' withdrawal
      presented within 72 hours (median 24 hours) and lasted for less than six days.
      Infants exposed to methadone had symptoms for longer but required less treatment
      than infants exposed to heroin. Forty infants needed treatment with
      phenobarbitone for a median of four days. Only six infants needed other drugs.
      Median age of discharge was 11 days and 49 out of 53 went home with their
      mothers. CONCLUSIONS: The Glaswegian polydrug pattern would make
      morphine/methadone unsuitable treatment. If these infants are not showing signs
      of withdrawal at 72 hours it is, in our opinion, reasonable to discharge them.
      Infants should not be discharged with outstanding problems, as follow-up is
      usually unsuccessful.

PMID- 12811885
TI  - CT brain scans after acute stroke: how far are we from meeting the Scottish
      intercollegiate guidelines network (SIGN) recommendations? Results from the year
      prior to guideline publication.
AB  - OBJECTIVE: To determine what proportion of patients admitted to Ninewells
      Hospital & Medical School in 1996 with acute stroke underwent CT brain scans and
      in what time frame. To decide if the targets set by the SIGN guidelines can be
      met, and if not, the reasons for this. DESIGN: Data from the Dundee Ninewells
      Stroke Register and the Computerised Radiology Information System were used to
      determine the timing of CT scanning in relation to stroke and admission. Notes
      were also reviewed to determine why CT scans had not been done in some patients.
      SETTING: Departments of Medicine and Radiology, Ninewells Hospital & Medical
      School Dundee. SUBJECTS: All patients admitted with acute stroke in the calendar
      year 1996. RESULTS: Two hundred and eighty six patients presented with acute
      stroke in 1996. Of these patients, 250 patients (87%) had a CT brain scan. Eighty
      three (29%) underwent CT brain scanning within 48 hours of the acute event. A
      total of 163 (57%) were scanned within a week. Two hundred and thirty three (81%)
      were scanned within three weeks. Thirty six patients were not scanned after their
      acute event and the reasons recorded are reviewed. CONCLUSIONS: Less than two
      thirds of patients were scanned within the time interval of seven days
      recommended in the SIGN Guidelines for stroke management. Implementation of the
      current SIGN Guidelines will therefore, require reorganisation of the service to
      ensure that all patients receive scans within seven and preferably within two
      days and may have resource implication.

PMID- 12811886
TI  - Can general practitioner referral letters for acute medical admissions be
      improved?
AB  - BACKGROUND: General practitioner (GP) referral letters for emergency medical
      admissions should contain enough information to ensure that patients are managed
      safely and effectively. AIM: Our aim was to assess the quality of referral
      letters for acute medical admissions. METHOD: GP letters from 300 consecutive
      acute medical admissions were prospectively assessed by the admitting doctor and
      then independently assessed by a senior house officer (SHO), and a senior
      registrar. A random sample of 25 were assessed by a general practitioner. Content
      and legibility were evaluated for demographic details, current history, past
      history, social history, drugs and allergies, in order to grade the overall
      quality as "excellent", "good", "adequate" or "inadequate". RESULTS: Two hundred
      and ninety one letters were received, of which 208 (71%) were from the patients'
      own GP practice and 83 (28%) from a co-operative or deputising service. The
      admitting doctor rated 38 (13%) as excellent, 108 (37%) as good, 96 (33%) as
      adequate and 49 (17%) as inadequate. Kappa values for overall quality between the
      admitting doctors and the other doctors (senior house officer, senior registrar
      and our general practitioner) were 0.32, 0.26 and 0.44 respectively, representing
      fair to moderate interobserver agreement. Co-operatives or deputising services
      used proformas more often than GP practices (65/83, 78% and 17/208, 8%
      respectively, p < 0.01). There was no significant difference in overall quality
      between GP practices and co-operatives or deputising services, or between letters
      received on headed note paper or proformas. CONCLUSION: Most letters are
      satisfactory for the individual management of acutely ill patients, but
      collaborative work could usefully be undertaken to address the factors which
      result in the production of sub-optimal referral letters.

PMID- 12811887
TI  - An examination of the pattern of challenging behaviour referrals to a community
      learning disability nursing service.

PMID- 12811888
TI  - When medicine meets the law--guidelines for decision making in acute medical
      admissions.

PMID- 12811889
TI  - Out of hours primary care: a critical overview of current knowledge.
AB  - Out of hours care in the UK has undergone radical changes in the past five years,
      with a rapid increase in the number of general practitioner co-operatives
      operating from primary care centres. Patients wishing to see a general
      practitioner outwith normal surgery hours can now be asked to attend a centre, be
      given telephone advice or may still receive a home visit if required. This
      overview examines the current literature evaluating these changes. While there
      are now a number of studies examining general practitioner co-operatives and
      centres in both England and Scotland, there is little or no work on other forms
      of out of hours care. In particular, little is known about the continuing role of
      the single handed general practitioner or about out of hours care in small towns
      and in rural areas. The need for these issues to be addressed is discussed and
      the aims of the current Scottish study comparing different models of out of hours
      care outlined.

PMID- 12811890
TI  - Knowledge of alcohol-related problems in clinical staff in psychiatric community
      resource centres in Glasgow.
AB  - We report on a survey of knowledge of alcohol-related problems in the multi
      disciplinary staff in 12 general adult psychiatry community resource centres. In
      total we obtained data from 111 staff, the majority of whom (63%) were community
      psychiatric nurses (CPNs). Seventy-three per cent of staff routinely ask clients
      about their alcohol consumption and 66% felt that they could identify those
      clients with an alcohol problem. We identified gaps in knowledge that could be
      seen as significant, for example, the legal driving limit and the number of units
      of alcohol in bottles of wine and spirits. Less than a third of staff knew the
      criteria for alcohol dependence. The majority of staff were able to recognise
      clinical complications of alcohol abuse and to identify alcohol withdrawal
      symptoms. We consider that it would be useful to provide a simple concise data
      sheet, containing basic information about alcohol, for clinical staff.

PMID- 12811891
TI  - Injuries in the adolescent population in Scotland: patterns and types of injuries
      sustained.
AB  - OBJECTIVE: To provide information on the incidence, sex distribution, type, site
      and severity of injuries requiring medical attention reported in a nationally
      representative sample of Scottish teenagers studied longitudinally. DESIGN:
      Health visitors administered structured interviews with parents (usually
      mothers). Quantitative data were analysed using SPSS-PC, and qualitative and
      textual data were coded using the Abbreviated Injury Score (AIS). SETTING:
      Scotland. SUBJECTS: Responses were received in respect of 958 (68%) of the
      estimated 1,416 teenagers enrolled in the British Cohort Study (BCS 70), and
      resident in Scotland in 1986/7. RESULTS: 43% of subjects were reported as having
      experienced one or more unintentional injury events requiring medical attention
      between the ages of 10 and 16/17. Boys experienced significantly more injuries
      than girls. Neither social class nor region appeared to be a significant risk
      factor for reported injury. CONCLUSION: Patterns of accidents in Scottish
      adolescents are reported. Further areas for study are suggested.

PMID- 12811892
TI  - A survey of general practitioners in north-east Scotland on practice-based
      counselling services.
AB  - OBJECTIVE: Practice-based counselors have become very numerous in primary care
      and we sought to elicit the views of general practitioners in north-east Scotland
      about the present situation and possible developments in practice-based
      counselling services. DESIGN AND SUBJECTS: A questionnaire was mailed to the 352
      general practitioners working in the area covered by Grampian Health Board.
      RESULTS: There was a 74% response rate: 46% of respondents had access to a
      practice-based counsellor and of those who did not, two-thirds wanted to acquire
      one. Larger practices and fundholding practices were more likely to have practice
      based counsellors. There was a lack of knowledge about the medico-legal situation
      when referrals to counsellors were made. Seventy-nine per cent of respondents
      thought that the need/demand for counselling would increase during the next
      decade, and a majority considered provision of counselling through mental health
      teams, with local co-ordination of accreditation, training and supervision, to be
      desirable. CONCLUSION: Since the efficacy of counselling for mental health
      problems in primary care has not been established, and provision of counselling
      in primary care settings continues to increase, there is a need to mount coherent
      and appropriate research studies. There also appears to be a need for greater
      integration between primary care and mental health services to generate rational
      provision of practice-based counselling.

PMID- 12811893
TI  - Audit of chest X-rays in general practice--a case for local guidelines?
AB  - OBJECTIVE: To investigate the use of the chest X-ray (CXR) in a typical urban
      practice with reference to the Royal College of Radiology (RCR) guidelines.
      DESIGN: A retrospective review of all requests over a two-year period. SETTING:
      Urban general practice with 9,463 registered patients. RESULTS: A total of 569
      CXRs were performed in 482 patients. Thirty per cent of the CXRs were assessed as
      being "not indicated" and a significant percentage of requests did not come
      within the RCR guidelines. The guidelines advise a six weeks' delay following
      onset of chest wall pain prior to chest X-ray. We assessed the application of the
      rule in this patient group. A large percentage of those X-rayed were referred at
      less than the recommended six weeks' interval from time of presentation and the
      vast majority of CXRs were entirely normal. The "six weeks rule" was developed
      further in patients with cough, differentiating between simple and productive
      cough. Those with productive cough who were otherwise well had no significant
      findings in contrast to the unwell group where several abnormalities were
      noticed. Radiology-recommended follow-up films were further studied. Where the
      CXR was carried out after a time interval of less than three weeks, several
      showed incomplete resolution and a further film was required. CONCLUSION: The RCR
      guidelines might be adapted to apply to those with simple cough or to those with
      productive cough who are otherwise well. This simple recommendation, in addition
      to the RCR guidelines, we feel would reduce the number of unnecessary CXRs
      performed in general practice.

PMID- 12811894
TI  - Impact on an accident and emergency department of Glasgow's new primary care
      emergency service.
AB  - OBJECTIVE: To determine the impact, in terms of new attendance figures and types
      of patients attending, on a city centre accident and emergency (A & E) department
      following the establishment of out-of-hours primary care emergency centres
      (PCECs) in Glasgow. METHODS: A questionnaire survey of A&E patients attending out
      of-hours at Glasgow Royal Infirmary A&E department, a city centre department with
      approximately 68,000 new annual attendances, one week before (Group A), twelve
      weeks after (Group B) and one year after (Group C) the introduction of PCECs.
      Main outcome measures were attendance numbers within working hours and out-of
      hours, reason for A&E attendance, duration of presenting condition, whether
      primary care services were contacted and awareness of the new primary care
      emergency centres. RESULTS: In respect of out-of-hours attendances, 612
      questionnaires were completed for group A, 715 for group B and 645 for group C.
      There was no significant difference in the type of presenting complaints between
      the groups, i.e. illness or injury. The majority of patients presented within 24
      hours of the onset of their condition (82%, 79% and 80% of patients in groups A,
      B and C respectively). There was a reduction in those attending with conditions
      of more than one week's duration (8% in group A, 7% in group B and 5% in group
      C). There was a decrease in the number of patients who considered their problem
      to be non-urgent (27% in group A, 22% in group B and 16% in group C). Prior to
      the introduction of the PCEC service 18% of patients (108) had contacted their GP
      before attending, compared with only 9% (63) of group B and 9% (57) of group C
      patients. Of these patients there was a significant decrease in the number of
      patients attending following GP referral. Of the patients who had not contacted
      the primary care services only 35% (201) knew of the introduction of PCECs 12
      weeks later, increasing to 52% (291) after one year (p < 0.01). Significance
      calculations were performed using a Difference of Proportion Test with a 99%
      significance level. CONCLUSIONS: Our results suggest that the new PCEC service
      has not had a significant impact on the number or type of patients attending this
      A&E department, with fewer self-referred patients contacting primary care
      services after its introduction. Following the introduction of the PCECs there
      was a trend towards more patients attending A&E following telephone advice
      although amongst self-referred A&E patients there remained a large proportion who
      claimed to be unaware of the new service 12 weeks after, and one year after, the
      introduction of PCECs. Continued evaluation of the effect on A&E of the new
      centres will be required to plan future resources for the provision of emergency
      care.

PMID- 12811895
TI  - Echocardiography in district general hospitals: trends over a five-year period
      1993-1998.
AB  - Postal surveys were carried out in 1993 and 1998 to establish the range and
      nature of echocardiography facilities within district general hospitals in
      Scotland. This study examines some of the changes over this five year period.
      Echocardiography services vary widely between hospitals. There have been
      substantial changes in the last five years, with increases in both the staff
      involved in echocardiography and in the number of investigations performed. The
      facilities available have improved and more respondents to the survey in 1998
      were happy with training than in 1993. Echocardiography has a major place in
      modern management of patients with cardiac problems. This survey provides a
      useful benchmark for comparison between services.

PMID- 12811896
TI  - Educating lay carers of people with learning disability in epilepsy awareness and
      in the use of rectal diazepam: a suggested teaching protocol for use by
      healthcare personnel.
AB  - A high proportion of people with learning disabilities have epilepsy and often
      their epilepsy is of an intractable nature. Nurses within the large learning
      disability institutions are obliged, on a regular basis, to administer rectal
      diazepam to control these patients' serial seizures. As a result of the
      "community care" initiative, the process of discharging adult people from
      institutions into care settings in the community is underway. Consequently, and
      increasingly, the learning disabled are being cared for by non-medical/non
      nursing (lay) community home carers who are required to gain a working knowledge
      of epilepsy as well as a degree of proficiency in the first aid management of
      seizures and in the use of rectal diazepam. Medical and nursing staff involved in
      the care of adults with learning disability are now liable to be approached by
      lay care organisations for appropriate training. This article, therefore, will
      outline the training programme employed at Gogarburn Hospital to educate lay
      community care staff in general epilepsy awareness and in the administration of
      rectal diazepam to adults with learning disability and epilepsy. This programme
      could be adapted and implemented by colleagues in their own areas.

PMID- 12811897
TI  - SIGN guidelines: an investigation into their value and use in contemporary
      nursing practice and education.
AB  - AIM: To explore the nature of SIGN clinical guidelines and the nurse teachers'
      role in supporting their dissemination and implementation within acute care
      nursing and subsequent curriculum design. DESIGN: The study consisted of a survey
      which employed three methods of data collection: a questionnaire, a semi
      structured interview and focus group interview. SUBJECTS AND SETTING: Those in
      Scotland directly involved in the teaching of nurses and midwives in pre- and
      post-registration programmes in higher education institutions (n = 635) and
      health care professionals (n = 49) currently working in the primary and secondary
      care setting. RESULTS: The findings from the questionnaire and focus group
      interviews suggest that nurse-teachers have limited knowledge of SIGN and that
      the integration of clinical guidelines in pre- and post-registration programmes
      is minimal. The findings from the interviews with a variety of health care
      professionals indicate the implementation of clinical guidelines is at an early
      stage in most trust areas and that education on their use is a major issue for
      practitioners. CONCLUSIONS: There is great potential for nurse educators to
      support the process of dissemination and implementation of clinical guidelines
      through their integration at every level of the curriculum. In this study both
      educators and clinicians (particularly in secondary care) were positively in
      favour of more information and education on SIGN clinical guidelines.

PMID- 12811899
TI  - Costing of healthcare for improving effectiveness.
AB  - There is increasing emphasis on clinical and cost-effectiveness in the Health
      Service, which is faced with rising demands and increasing opportunities but
      limited resources. Cost-effectiveness analysis requires reliable data on both
      clinical effectiveness and costs. This paper examines some of the issues involved
      in analysing costs for improving effectiveness, such as the realities of
      realising theoretical savings, for example when a new drug reduces hospital
      admissions.

PMID- 12811900
TI  - The Scottish Centre for Infection and Environmental Health (SCIEH).
AB  - The Scottish Centre for Infection and Environmental Health has four core
      functions: the monitoring and surveillance of communicable diseases and
      environmental hazards in Scotland; operational advice and support at national and
      local level; research; and education and training. Its work is determined by a
      specification drawn up by the Public Health Policy Unit of the Scottish Office
      Department of Health. To fulfill its remit it works closely with a wide range of
      professionals, including those in the Scottish Office Department of Health, the
      health service, local government, and in organisations concerned with the
      environment. It also has close relationships with the Communicable Disease
      Surveillance Centre, Public Health Laboratory Service, London, the World Health
      Organization and other international bodies.

PMID- 12811901
TI  - Bed-blocking in the National Health Service in Scotland: a study of bed-blocking
      in Scottish National Health Service trusts; its nature and extent.
AB  - OBJECTIVE: To determine the perceptions of managers in Scottish NHS trusts
      concerning bed-blocking. To help determine the causes of bed-blocking and suggest
      possible solutions to the problem. DESIGN: The first part of the study consisted
      of qualitative research interviews with key figures in NHS trusts and an
      examination of the existing literature on bed-blocking. This informed the second
      stage which was based on a questionnaire survey of senior managers in 35 trusts.
      SETTING: Interviews were carried out in three trusts in Forth Valley Health Board
      and Grampian Health Board areas. Questionnaires were sent out to 44 trusts
      throughout Scotland. The three trusts that were excluded from this study did not
      contain bed-blocking patients. SUBJECTS: Questionnaires were sent to chief
      executives of 44 NHS trusts in Scotland. Respondents were nominated by chief
      executives on the basis of their experience and understanding of bed-blocking
      problems within their own trust. RESULTS: Of the 44 questionnaires sent to trusts
      in Scotland, there were 35 responses (80%) which identified a total of 1845 beds
      as being blocked. The NHS secondary care-based respondents indicated that social
      services were responsible for 1406 bed-blocking patients in 35 trusts, an average
      of 40 patients per trust between August and September 1997. Some 600 of these
      "social services responsible" bed-blocking patients, an average of 21 patients
      per trust, were reported as awaiting comprehensive assessment by a social worker.
      In addition, 710 of these "social services responsible" bed-blocking patients, an
      average of 24 patients per trust, were awaiting funding authorization for a
      nursing home or residential home placement. NHS trusts were responsible for 237
      bed-blocking patients, an average of seven patients per trust. In a further 202
      cases bed-blocking was deemed to be neither the responsibility of the trust nor
      of social services as patients were awaiting vacancies in the patient's or
      carer's specific choice of residential or nursing home. CONCLUSION: Results from
      this study show that there would appear to be a significant number of blocked
      beds in NHS trust hospitals throughout Scotland. Trust staff, whilst
      acknowledging the complex nature of bed-blocking, perceive social services, who
      are responsible for the assessment, placement and financing of patients being
      transferred from hospitals to residential care in the community, as being
      responsible for the majority of these beds being blocked. It is, however,
      acknowledged that social services are under-funded and under-resourced. If the
      situation is to be improved, consideration should be given to changing service
      delivery processes in the context of the implementation of Designed to Care.

PMID- 12811902
TI  - Re-organising emergency medical admitting: the Stobhill experience, 1992-1997.
AB  - OBJECTIVE: To examine patterns of acute medical emergency admissions and the
      effect of reorganisation on their management. DESIGN: Examination of statistics
      for emergency medical admissions from 1992 to 1997, a period that included a
      major reorganisation of the emergency admitting system within the hospital.
      SETTING: General hospital in a Scottish conurbation. RESULTS: There was a slow
      annual increase in numbers of admissions during the period of study with very
      considerable variations in daily and weekly numbers of admissions. Reorganisation
      achieved a reduction in average length of stay from seven to 4.5 days permitting
      reduction of the bed complement from 223 to 161. Following reorganisation, 31% of
      admissions were discharged home within 48 hours directly from the acute medical
      receiving ward, 18% of admissions were transferred directly to care of the
      elderly, and 33% of admissions were transferred to medical wards. Patient and
      staff satisfaction surveys indicated preference for the new system over the old.
      Admission peaks over the winter months of the last three years occurred at
      different weeks in the year. CONCLUSIONS: Reorganisation of the medical admitting
      system can improve efficiency and allow reductions in staffed beds. The
      considerable [table: see text] variation in daily demands in the system makes it
      important to retain flexibility. There may be scope for dealing with the large
      numbers of short-term admissions in other ways.

PMID- 12811904
TI  - Quality here, there and everywhere: the application of a multi-dimensional
      learning tool to learning disability health services.
AB  - The following paper examines the applicability of Maxwell's Multi-dimensional
      Quality Evaluation model to community learning disability health services. The
      model defines seven dimensions against which the quality of any given service can
      be measured: effectiveness, efficiency, economy, equity, access to services,
      appropriateness and social acceptability. A number of examples in relation to
      community learning disability services are discussed.

PMID- 12811903
TI  - Clinical record keeping in patients receiving antibiotics in hospital.
AB  - BACKGROUND: Antibiotic prescribing is associated with the growth of antibiotic
      resistance in micro-organisms. Prescribing therefore needs to be restricted by
      well-designed antibiotic protocols. Audit of such protocols is only possible if
      clinical information about infection is properly recorded. OBJECTIVE: To assess
      the quality of clinical data recording in case notes of patients receiving
      antibiotics in hospital and to assess the effect of feedback of this information
      on clinical practice. DESIGN: Four point prevalence surveys. SETTING: Directorate
      of General Medicine, Dundee Teaching Hospitals NHS Trust. SUBJECTS: Inpatients
      receiving antibiotics. INTERVENTION: Feedback of results from the first two
      surveys to clinicians. MAIN OUTCOME MEASURES: Proportion of patients in the
      Medical Directorate with the recording of an antibiotic indication and the
      temperature in the case notes before, immediately after, and three months after,
      feedback of survey results. RESULTS: In each survey one third of patients were
      receiving antibiotics. The antibiotic indication was recorded in 64% of patients
      prior to feedback and in 86.5% after feedback (p = 0.004). Three months later
      this had fallen to 74%. Temperature recording improved between 2nd and 3rd
      surveys (57% to 86.1%, p < 0.001) and declined to 61% in the 4th survey (p <
      0.001). Respiratory infection was the commonest recorded indication for an
      antibiotic; recording of this indication improved between the 2nd and 3rd surveys
      but declined by the 4th survey. CONCLUSIONS: Audit and feedback of information
      about clinical record keeping improves standards but improvements are not
      sustained. Clinical record keeping must be improved so compliance with antibiotic
      protocols can be properly audited. An "antibiotic sticker" in addition to
      immediate concurrent feedback may improve such deficiencies.

PMID- 12811906
TI  - Low dependency residents in private nursing homes in Glasgow.
AB  - OBJECTIVES: To investigate why nursing home care had been recommended for elderly
      people who were assessed subsequently as being of low dependency. DESIGN:
      Examination of community care assessment documentation for low dependency
      residents to assess reasons for recommending nursing home care; comparison of
      these with data from a subsequent SCRUGs (Scottish Care Resource Utilisation
      Groups) assessment. SETTING AND SUBJECTS: Three hundred and four residents within
      eight private nursing homes in Glasgow. RESULTS: Twenty six percent of the
      residents were described as being of low dependency. Of these, 44% had dementia
      and 6% personal care needs alone; 29% had medical problems which required nursing
      input, but not necessarily to a level requiring nursing home care. Information in
      the community care assessment often described a higher level of need than that
      identified subsequently. From the information given in the medical component of
      the community care assessment it was often unclear why the decision to recommend
      nursing home care was made. CONCLUSION: Admission to nursing homes may be
      encouraged by over-emphasiZing care requirements, by placing emphasis on safety
      rather than independence and by inadequate recording of information. Elderly
      people who cannot remain at home need improved assessment procedures, better
      understanding of their needs and a wider range of accommodation options.

PMID- 12811908
TI  - Monitoring breastfeeding rates and setting local targets: the Glasgow experience.
AB  - OBJECTIVE: The objective was to provide baseline data on infant feeding intention
      and practice in Glasgow. DESIGN: Information was collected from a prospective
      cohort of women who booked for maternity care in Glasgow during the months
      November 1995 and May 1996. Figures on feeding intention and practice were
      collected at five points from maternity booking until six weeks postnatal age.
      SETTING: Women were recruited at the four maternity units in Glasgow. Follow-up
      information was collected at birth, discharge from the maternity hospital at four
      days, and then at 12 days at home by the community midwife, and finally at six
      weeks by the health visitor. SUBJECTS: One thousand seven hundred and ninety two
      women were recruited at maternity booking. Breastfeeding information was
      available at birth for 1723, at discharge for 1743, at 12 days for 1513, and at
      six weeks for 1394. Multiple logistic regression determined maternal and infant
      factors predicting feeding intention and duration. RESULTS: At booking 50%
      planned to breastfeed. Fifty percent breastfed at birth; by four days the rate
      had dropped to 42%, by 12 days to 36% and by six weeks to 27%. Five factors:
      deprivation score, maternal age, parity, maternal smoking and previous
      breastfeeding experience independently predicted feeding intention. Maternal
      factors explained differences in breastfeeding rates between the four hospitals.
      CONCLUSION: Original breastfeeding targets for Glasgow have been revised to take
      account of local circumstances. An alternative method using routinely collected
      data is needed to monitor progress.

PMID- 12811907
TI  - Independent nursing practice: a national survey of attitudes of practice employed
      nurses in Scotland.
AB  - BACKGROUND: During the last decade, the number of practice nurses has increased
      dramatically and their role has evolved according to demand rather than through
      planning and design. Consequently, many nursing roles have become extended and
      nurses now perform many of the tasks previously performed by doctors. With
      increasing emphasis on primary care, their new role has become widely accepted
      and continues to develop. There is now a real question as to whether, with
      suitable training, it is timely to consider a formal extension to independent
      practice for at least some practice nurses. OBJECTIVE: The aim was to describe
      the characteristics of practice nurses and to explore their attitudes to
      independent practice. For the purpose of this study, independent practice was
      taken to mean specialised autonomous practice. DESIGN: This was a descriptive,
      cross-sectional study undertaken by postal questionnaire. A two stage sampling
      process was used. SETTING: Firstly a 1/2 sample of all general practices in
      Scotland (n = 625) was asked for the names of all practice employed nurses.
      Secondly, one practice nurse from each practice was sent a postal questionnaire.
      RESULTS: Five hundred and thirty eight general practices responded. Eighty six
      practices had no practice employed nurse. Four hundred and thirty three practices
      (96%; 433/452) were willing to allow their practice nurses to be approached to
      take part in the study. Four hundred practice nurses returned questionnaires
      (92%; 400/433). Fifteen were excluded because the nurses were not fully practice
      employed. Three hundred and eighty five were suitable for inclusion in the study
      (85%; 385/452). Most practice nurses were over 35 years of age and had been in
      post for more than three years. Almost half had at least one other nursing
      qualification in addition to registration. Eighty six percent thought that there
      should be independent practice for some nurses within the profession and 65%
      would, themselves, be happy to practise independently. CONCLUSION: Most practice
      nurses throughout Scotland think that there should be independent practice for
      some nurses.

PMID- 12811909
TI  - Assessing dissatisfaction with an out of hours service: reasons and remedies.
AB  - OBJECTIVE: To identify characteristics associated with dissatisfaction following
      contact with an out of hours co-operative in Glasgow, and to identify reasons for
      this dissatisfaction. To make recommendations for good practice in the light of
      these findings. DESIGN: Survey of attenders during one week of operation of an
      out of hours co-operative. Analysis of factors associated with dissatisfaction.
      SETTING: The Glasgow Emergency Medical Service, October 1996. SUBJECTS:
      Questionnaires were received from 1115 patients or their carers, representing a
      69.3% response rate. RESULTS: Dissatisfaction was associated with unmet
      expectations, particularly among those expecting home visits. Parents of young
      children, more affluent patients, and those experiencing problems with daytime
      services also tended to be dissatisfied. Seventy four (7%) respondents indicated
      that they were very dissatisfied with aspects of the service. A high proportion
      of this dissatisfaction was related to telephone contact. Transport to out of
      hours centres caused problems for some patients, particularly for those with
      young children. Perceptions of dismissive attitudes by medical staff, and of
      incorrect diagnoses and treatment were causes of strong dissatisfaction. Patients
      with adverse medical outcomes were also likely to be very dissatisfied.
      CONCLUSION: Clear reasons for dissatisfaction were found among our sample. In
      most cases, remedial management action could be taken to reduce the likelihood of
      major dissatisfaction with the service.

PMID- 12811910
TI  - Restoration of primary teeth: a study of copper phosphate cement.
AB  - OBJECTIVE: To determine the survival of 'PD' Black Copper Cement when used as a
      dental filling material in carious primary teeth. DESIGN: A prospective study.
      SETTING: Dundee Dental Hospital, Dundee. SUBJECTS: Fifty children with carious
      primary molars had 82 dental restorations placed in the initial study. For the
      follow-up study, 45 restorations were available. RESULTS: Over 65% of the Black
      Copper Cement restorations placed in the initial study failed. Modification of
      restoration technique reduced the total loss of filling material to 18% of cases.
      CONCLUSION: To take advantage of the cariostatic properties of black copper
      cement may require it to be used as a lining under a less soluble restorative
      material.

PMID- 12811911
TI  - Pneumococcal disease and asplenia: the importance of vaccination.
AB  - Pneumococcal disease is an important cause of morbidity and mortality,
      particularly in certain patient groups including those who have been
      splenectomised or have no functioning spleen. Recent deaths in two asplenic
      patients from pneumococcal disease should remind doctors of the importance of
      vaccination in asplenic individuals. The current guidelines for vaccination in
      such patients are highlighted and discussed. The need for a national asplenic
      register is also suggested.

PMID- 12811912
TI  - Child and adolescent forensic psychiatry survey--in Scotland.
AB  - OBJECTIVES: To review the provision of Adolescent Forensic Services, and assess
      the need for the development of a separate service as exists for adult mentally
      disordered offenders. DESIGN AND SUBJECTS: To investigate by postal survey to all
      child and adolescent psychiatrists in Scotland. RESULTS: There is a lack of
      forensic adolescent expertise in Scotland and a perceived need for it. Child and
      adolescent psychiatrists are required to deal with difficult forensic cases,
      without appropriate training. CONCLUSION: A child and adolescent forensic service
      for Scotland needs to be developed.

PMID- 12811913
TI  - Getting research evidence into practice.

PMID- 12811914
TI  - Breast cancer audit: adapting national audit frameworks for local review of
      clinical practice.
AB  - OBJECTIVE: To assess the value of using a nationally devised data set for breast
      cancer audit at a local level for reviewing clinical practice. DESIGN: Audit
      proforma based on the Scottish Cancer Therapy Network (SCTN) minimum data set and
      database completed prospectively from January 1999. SETTING: Hairmyres Hospital,
      a district general hospital within Lanarkshire Acute Services NHS Trust.
      SUBJECTS: The inclusion criteria were those developed by SCTN for the core
      minimum data set for breast cancer (SCTN 1999). RESULTS: The results indicate
      that the SCTN minimum data set can be usefully employed to collect prospective
      data on breast cancer. The data set is sensitive enough to identify any problem
      areas, which can be reviewed at greater detail when required. This datset is a
      robust mechanism for collecting meaningful and comparable data both at a local
      and national level. CONCLUSIONS: The use of SCTN's minimum data set has been
      successful for local review of practice. This has led to the identification of
      "out-liers" from the normal range of process indicators and further internal
      examination of these at a local level by individual clinicians is under way. This
      exercise has also proved fruitful in identification of other fields, which can be
      added to the data set to refine the data collected. The database provided by SCTN
      is easily manipulated allowing for refinement where required. Breast cancer audit
      carried out in this way is a useful way of reflecting on clinical practice
      throughout the multidisciplinary team.

PMID- 12811915
TI  - [Scope of lymphadenectomy in organ-sparing operations in kidney cancer patients].
AB  - Organ-saving operations (extended lymphadenectomy) were performed in 125 patients
      with renal carcinoma (RC) in the urological clinic of I. M. Sechenov Moscow
      Medical Academy between 1992 and 2002. In view of specific segment-by-segment
      lymph flow off the right and left kidneys, it is thought valid to remove
      paracaval and aortocaval lymph nodes in saving operations on the right kidney but
      in cancer of the left kidney it is recommended to remove paraaortic lymph nodes.
      Basing on the anatomical features, lympho-dissection should be made from the crus
      of the diaphragm to bifurcation of the aorta. Metastases to the regional lymph
      nodes were diagnosed in 12 (9.6%) patients. In 8 of 12 patients with pN+ lymph
      node metastases were microscopic. Frequency of lymphogenic metastases directly
      correlated with the size and stage of the tumor, cancer cells differentiation
      degree. Metastatic involvement of the regional lymph nodes in renal cancer is an
      unfavourable prognostic factor as 5-year survival for the overall group of
      patients was 71.7% while for patients with pN+ it was 41.7%.

PMID- 12811916
TI  - [Surgical treatment of bilateral renal cell carcinoma].
AB  - The paper presents the results of surgical treatment of bilateral tumors of the
      kidneys. Bilateral neoplasms were detected in 28 of 1200 patients with renal cell
      carcinoma (2.3%). Synchronous tumors were found in 12 patients (42.8%),
      asynchronous--in 16 (57.2%). Operation on both the kidneys for tumor was carried
      out in 21 patients from 28 (75%). In both groups operations including enucleation
      of the tumors (60% in the group with synchronous cancer and 53.8%) in the group
      with asynchronous one) prevailed. All the patients were operated in two stages.
      Local relapses occurred in 6 of 21 patients (28.5%). A relapse after nephrectomy
      was observed in 2 patients (9.5%). Recurrent tumor in the remnant of the kidney
      after nephron-sparing surgery was observed in 4 patients (19%). General 5 year
      survival in patients with synchronous bilateral tumors was 38.5%, whereas 5-year
      cancer-specific survival reached 47.4%. For asynchronous cancer these parameters
      were 49.6 and 58.7%, respectively. It is emphasized that all patients with renal
      cancer after radical nephrectomy should be followed up and undergo annual check
      up with US and/or CT lifelong to detect possible asynchronous tumor. Genetic
      studies are necessary to specify differentiation of the form of bilateral
      neoplasm.

PMID- 12811917
TI  - [Radical prostatectomy: surgical techniques and preliminary results].
AB  - Prostatic cancer (PC) is a frequent finding in aged men. In fact, 3% of males
      have the chance to die of PC. Radical prostatectomy by the retropubic approach
      with pelvic lymphadenectomy was made in 97 males. The treatment was performed in
      the urological department of the MSMSU urological chair from 1995 to 2001. 69
      patients followed up for 3-64 months after the operation were eligible for
      analysis of the outcomes. The patients had the following PC stages: T1--11
      patients, T2--44 patients, T3--14 patients. Prostate-specific antibodies ranged
      within 2.9-67.8 ng/ml (the mean level 16.7 ng/ml). The results of the treatment
      were satisfactory in 65 (94.2%) of 69 patients. The operation did not take more
      than 2.5 hours, mean blood loss was under 870 ml. Adequate urination after the
      catheter was removed resumed in 41 (59.4%) of 69 patients. Active urinary
      incontinence was observed within one year after the operation in 25 (36.2%)
      patients, total incontinence--in 3 (4.3%) patients. 51% patients retained the
      erectile function after nerve-sparing operation. Most of the patients had an
      unevenful postoperative period. During the follow-up 3 patients died of acute
      myocardial infarction (n = 1), intestinal cancer (n = 1) and distant PC
      metastases (n = 1). A postoperative fall in the PSA level under 0.3 ng/ml
      occurred in 49 (71%) patients, under 2 ng/ml in 7 patients (10%). In 19% of
      patients with pT2-3 the PCA rose over 2.0 ng/ml. Radical prostatectomy is
      indicated for patients with local prostatic cancer (stage T1 or T2) and probable
      survival from 10 to 15 years and longer. A nerve-sparing, sphincter-sparing and
      ablastic variant of this operation is widely used world-wide and is a method of
      choice for therapy of patients with retropubic prostatic cancer.

PMID- 12811918
TI  - [Paratesticular rhabdomyosarcoma].
AB  - Paratesticular rabdomyosarcoma (PR), the most frequently occurring paratesticular
      tumor, is encountered mostly in young and middle-aged men. PR metastasizes early
      and is characterized by lymphogenic dissemination of the tumor with affection of
      the retroperitoneal lymph nodes. Orchofuniculectomy is the first-line treatment
      in all the patients. If the patient is metastases-free it is followed by
      preventive retroperitoneal lymphadenectomy with subsequent adjuvant
      chemoradiotherapy. In disseminated PR, combined treatment is indicated including
      surgical removal of metastatic foci and adjuvant chemo- or chemoradiotherapy. If
      surgical removal of all the tumor foci is infeasible, patients with disseminated
      PR undergo chemotherapy. Radiation of metastatic retroperitoneal lymph nodes is
      uneffective. Prognosis of PR depends on the age, stage of the disease and
      treatment.

PMID- 12811919
TI  - [Systemic approach to diagnosis and treatment of sexual disorders, presenting as
      erectile dysfunction].

PMID- 12811920
TI  - [Etiopathogenetic basis for using magnetolaser therapy in the complex treatment
      of male infertility].
AB  - Up to 12-15% couples are infertile. The "responsibility" for infertility rests
      with the husband in 40-45% cases. The effects of routine drug therapy (n = 95) on
      a generative function are compared to those of magnetolaser therapy (n = 93) in
      188 males with excretory-inflammatory infertility suffering from chronic
      prostatitis. Low-intensity laser infra-red radiation was used in a permanent
      magnetic field produced by Azor-2K unit. The magnetolaser therapy more
      significantly than the routine therapy raised concentration and number of mobile
      forms of the spermia, reduced their degenerative forms, elevated the level of
      serum sexual and gonadotropic hormones. In 1 year pregnancy occurred in 41.7 and
      55.4% of 83 and 87 families (groups 1 and 2), respectively. The delivery took
      place in 35.8 and 49.7%, respectively.

PMID- 12811921
TI  - [Anti-inflammatory, antimicrobial and antidesquamative effect of "Uro-Biofon" in
      treating sexually transmitted urogenital infections].
AB  - The antiinflammatory reaction in patients with sexually transmitted urogenital
      infections (STUI) was assessed by the leucocyte count, causative agents, amount
      of lecitin particles and pH in prostatic secretion. Great amount of desquamated
      epithelial cells indicated natural death of epitheliocytes and tissue necrosis.
      These processes were traced in the course of different treatments. Standard
      therapy in combination with the antimicrobial drug (AMD) and URO-Biophon
      radiation (UBR) produced the highest effect in patients with chronic
      urethroprostatitis. This promoted reduction in the number of leukocytes, removal
      of epithelial cells, elimination of the microflora and an increase in the number
      of lecitin particles. Among patients with chronic urethritis effective levelling
      of the leukocytic reaction was observed in patients on the standard therapy or
      with UBR alone, or AMD alone. By the intensity of epithelial desquamation the
      result was highest in the control group. The highest microbiological disinfection
      effect was achieved in using combination of the above methods.

PMID- 12811922
TI  - [Change in indicators of metabolism and kidney function in intact rats after
      parenteral administration of sodium hypochlorite].
AB  - The changes of kidney metabolism, function and enzymuria activity of nephron
      epithelium cells after 4 days of parenteral administration of sodium hypochlorite
      0.02% and 0.06% solutions were investigated in the experiments on 15 intact non
      inbred rats of 200-280 g body weight. It was revealed that sodium hypochlorite
      induced metabolic damage to the kidney similar to ischemic one. The 0.02 and
      0.06% solutions of sodium hypochlorite administered parenterally produced no
      negative effect on renal function. There was no significant rise of enzymuria
      activity in experimental groups compared to the controls. Moreover, enzymuria of
      four from six nephron epithelium cell enzymes decreased significantly to day 5 of
      the experiment. Metabolic damage and enzymuria activity changes were more
      pronounced in rats given parenteral 0.06% solution of sodium hypochlorite.

PMID- 12811923
TI  - [Repeat operation to correct the ureteropelvic segment in hydronephrosis in
      children].
AB  - The results of surgical correction of 487 ureteropelvic segments (UPS) were
      studied in 455 patients (age 4 months to 15 years). Good results were obtained in
      correction of 477 (98.0%) UPS including 12 after reoperation. Postoperative
      follow-up lasted for 1 to 25 years. Anastomosis obstruction observed in 12
      patients had developed within several postoperative months. In 3 patients it
      appeared 2-14 years after an effective UPS correction. The obstruction resulted
      from cicatricial transformation of the ureter and aduject fat with or without
      obliteration of the anastomosis or ureteral transformation into a rigid
      connective tissue tube unable to carry the functional load. One of the reasons of
      connective tissue transformation of the ureter may be urine leakage of the
      anastomosis. An individual reaction to the suture material (catgut) followed by
      scar process is also possible. Development of destructive changes many years
      after successful correction of UPS may arise due to inflammatory process ending
      in sclerosis. Some moments in pathogenesis of scar transformation of the ureter
      remains unknown and need further studies. Repeated correction of UPS was
      effective in all 15 patients. This intervention should be performed at least
      after 5-6 months after the failure of the first operation. To prevent the scar
      process, the patients must be followed up for many years and therapeutic methods
      should be perfected.

PMID- 12811924
TI  - [Experience of surgical treatment of webbed penis in children].
AB  - The webbed penis (WP) belongs to a rare and little-known defect of the external
      genitalia. The term denotes the penis of normal for age size hidden in the
      adjacent scrotal and pubic tissues. The authors describe clinical symptoms of the
      disease, consider anatomomorphological features underlying development of the WP,
      propose the WP classification including three basic clinical forms of this
      malformation, outline principles of diagnosis and differential diagnosis with the
      conditions associated with a small-size penis, analyze surgical treatment of 30
      boys with WP, surgical techniques in each form of the disease with adjustment for
      anatomic features, provide follow-up outcomes in the treated patients.

PMID- 12811925
TI  - [Intermittent bladder-ureteral reflux in children].
AB  - Basing on the results of a combined clinical and laboratory examination of 193
      children treated in the Research Institute of Urology in 1992-1999, the authors
      studied causes underlying intermittent vesicoureteral reflux (IVR) in correlation
      with anatomo-functional changes in vesicoureteral anastomosis and severity of
      inflammation in the urinary bladder. They suggest a diagnostic algorithm of
      detecting IVR with assessment of gas cystography role in the diagnosis; give
      definition of IVR; describe therapeutic policy in accordance with functional
      state of the affected kidney and cause of IVR onset; analyse short- (6-12 months)
      and long-term (12-36 months) treatment results; outline methods of IVR
      prophylaxis to save and improve renal function.

PMID- 12811926
TI  - [Clinical significance of profilometry of the pyeloureteral segment in congenital
      hydronephrosis in children].
AB  - Examination of hydrodynamic condition of the upper urinary tracts with step-by
      step pyelomanometry and profilometry of the pyeloureteral segment in 26 children
      at the age of 6 to 14 years with hydronephrosis provided topical diagnosis of the
      obstruction level. The priority role of the pelvis in development of obstructive
      urodynamic disorders was ascertained in 9 children. In the rest 17 children
      urodynamic disorders were determined by a different degree of obstruction in the
      prepelvic ureter. This urodynamic study may be essential for design of new
      approaches to choice of treatment method in the context of pathogenesis of
      hydronephrosis development.

PMID- 12811927
TI  - [Plastic surgery of the proximal segment of the right ureter after gunshot wound
      of the appendix].

PMID- 12811928
TI  - [Dermoid cyst of the testis].
AB  - The article reports a case of dermoid cyst of the left testis in a 18-year-old
      young man. The cyst contained masses of fat, a great number of hairs, multilayer
      squamous epithelium. The cyst was removed with preserving 1/2 of testicular
      parenchyma. The examination 3 years after the operation found no local
      recurrence, the spermogram was normal. 10 literature cases are analysed. Basing
      on these 10 cases, available in Russian medical literature, and one own case, the
      authors analyse clinical, diagnostic and therapeutic aspects of dermoid
      testicular cysts.

PMID- 12811929
TI  - [New endoscopic technologies in treating benign prostatic enlargement].

PMID- 12811930
TI  - [Laser surgery in urology].

PMID- 12811931
TI  - Ambulatory surgery center proposals bring mixed response from OIG.

PMID- 12811932
TI  - FAQs on releasing patient information to the media under new HIPAA privacy regs.

PMID- 12811933
TI  - Workplace injuries and illness.

PMID- 12811934
TI  - Bringing health care to the uninsured.

PMID- 12811935
TI  - Access to quality training is a priority.

PMID- 12811936
TI  - [Carole Deschambault. Managing change. Interview by Dominique Laliberte].

PMID- 12811937
TI  - [Quality of care. What is the attitude of chronic obstructive lung disease
      patients?].

PMID- 12811938
TI  - [Asepsis and wound care].

PMID- 12811940
TI  - [Preventing hypothermia in multiple trauma patients].

PMID- 12811941
TI  - [Shortage of nurses and benefits].

PMID- 12811942
TI  - [At the crossroads of research and practice. Interview by Danielle Graton].

PMID- 12811943
TI  - Quality of life and femoral neck fractures.
AB  - The worldwide increase in hip fractures is a major challenge to the health care
      system and society. The proper treatment of femoral neck fractures in the elderly
      is still controversial, and even more so from an international perspective.
      Optimising the treatment for improved outcomes and a reduced need for secondary
      surgery is mandatory for humanitarian and economical reasons. The importance of
      incorporating the patient's perspective of the outcome in clinical trials has
      been acknowledged and there are now numerous instruments for assessing the
      quality of life. We evaluated two quality of life instruments, the EQ-5D and the
      SF-36, in patients with femoral neck fractures and also measured the quality of
      life two years after different interventions. The EQ-5D was validated in two
      prospective studies and it appeared to be an appropriate quality of life
      instrument in elderly patients with femoral neck fractures. There was a good
      correlation between the quality of life (EQ-5Dindexscores) and other outcome
      measures such as pain, mobility and independence in activities of daily living
      (ADL). The results also showed high responsiveness, i.e., ability to capture
      clinically important changes, for both the EQ-5D and the SF-36. The questionnaire
      response rate for both instruments was high. The rated prefracture EQ
      5Dindexscores showed good correspondence with the scores of an age-matched
      Swedish reference population. The quality of life in patients with femoral neck
      fractures treated with internal fixation (IF) decreased, particularly in patients
      with fracture healing complications. The fracture healing complications rate at
      two years in patients with displaced femoral neck fractures treated with IF was
      36% compared with 7% in patients with undisplaced fractures. The quality of life
      of patients with uneventfully healed fractures at two year was lower in patients
      with primary displaced fractures than in patients with primary undisplaced
      fractures. In a prospective randomised trial, patients with displaced femoral
      neck fractures were randomised to IF or total hip replacement (THR). IF resulted
      in more complications than THR, 36% versus 4%, and necessitated more
      reoperations, 42% versus 4%. Hip function and quality of life (EQ-5D) were
      generally better in the THR group. In summary, THR yielded a better outcome than
      IF for an elderly, relatively healthy, lucid patient with a displaced femoral
      neck fracture. In a study of elderly women with femoral neck fractures, nearly
      half of the patients displayed signs of protein-energy malnutrition. Underweight
      was associated with muscle fatigue, cognitive dysfunction and a low quality of
      life (Nottingham Health Profile). In a prospective randomised trial, protein-rich
      liquid supplementation in combination with an anabolic steroid given for 6 months
      to lean elderly women after a femoral neck fracture was shown to positively
      affect lean body mass, ADL and quality of life (EQ-5D). Fracture healing
      complications had a negative impact on body weight, lean body mass and quality of
      life.

PMID- 12811944
TI  - From Michelangelo to Darwin: the evolution of human longevity.

PMID- 12811945
TI  - Geriatrics in the new millennium, Israel.
AB  - Since the early 1980s demographic changes compelled Israel's health system to
      dedicate efforts to establish modern geriatric services. This task was performed
      with the help of governmental and non-governmental institutions and was
      coordinated by the Division of Geriatrics and Long-Term Care Diseases of the
      Ministry of Health. Today, 20 years later, as a result of those efforts,
      geriatrics and geriatric services in Israel are thriving. Qualified staff,
      including physicians who specialized in geriatrics, are working to maintain a
      high quality of care in various geriatric settings. However, more resources
      should be allocated for research in order to maintain and to continue to develop
      geriatric medicine in Israel.

PMID- 12811946
TI  - Quality of life and social support following distal arterial bypass in elderly
      patients.
AB  - BACKGROUND: The chronic progressive course of peripheral arterial occlusive
      disease with its limb-threatening and life-threatening potential is associated
      with physical, psychological and social distress for elderly patients and their
      families. OBJECTIVE: To evaluate the influence of infra-inguinal bypass surgery
      for limb salvage, and social support, on quality of life in elderly patients
      (over 60 years old). METHODS: Sixty patients aged 60 years and above diagnosed
      with limb-threatening ischemia were evaluated using the SF-36 generic
      questionnaire for quality of life, and the MOS-SS questionnaire for social
      support. Thirty patients (group I) were evaluated in the hospital prior to
      reconstructive surgery and 30 postoperative patients (group II) were evaluated at
      home at least 6 months after infra-inguinal bypass operations. Both groups were
      comparable in terms of age, gender, prevalence of ischemic heart disease,
      diabetes, and other athero-sclerosis risk factors. RESULTS: All quality of life
      parameters were higher among patients who underwent limb salvage surgery (group
      II) as compared to preoperative patients (group I), yet the obtained values were
      lower than those in the general population. Patients in the surgical intervention
      group had higher levels of function, lower pain levels, and higher emotional and
      social well-being and, in addition, were spared limb amputation. The findings
      also indicate that the social support dimensions (emotional support, receipt of
      information, affection and positive social interaction), as measured in terms of
      perceived availability, do not operate as one entity. Different types of social
      support were more beneficial along different stages of the disease. CONCLUSION:
      Peripheral arterial occlusive disease causes severe impairment of the quality of
      life in elderly patients. Arterial reconstructive surgery improves the quality of
      life though it still remains low compared to the general population. Social
      support is beneficial in the treatment of these patients, and the social worker
      in the vascular surgery department has a key role in identifying the various
      needs of the patients along the path of their chronic illness.

PMID- 12811947
TI  - Focused, minimally invasive radio-guided parathyroidectomy: a feasible and safe
      option for elderly patients with primary hyperparathyroidism.
AB  - BACKGROUND: Primary hyperparathyroidism in elderly patients is usually associated
      with additional co-morbidity that increases operative risk, and thus many
      geriatric patients are denied the benefit of surgery for a single parathyroid
      adenoma. OBJECTIVES: To evaluate the safety and efficacy of accurate single
      photon emission computed tomography sestamibi scintigraphy, enabling precise
      localization of a single adenoma, in the geriatric population. METHODS: Twenty
      two patients aged 70 years and over with biochemically proven PHPT and with a
      single parathyroid adenoma identified by localization studies (sestamibi SPECT
      scan and ultrasonography) underwent 23 operations over 29 months (out of a total
      of 140 patients operated upon during the same period). Immediate preoperative
      sestamibi scintigraphy and marking of focal adenoma uptake followed by
      intraoperative hand-held gamma probe were used for the removal of the parathyroid
      adenoma by unilateral minimal access surgery. Associated major co-morbid
      conditions and pre- and postoperative calcium, phosphorus and parathormone levels
      were recorded. Indications for surgery were listed and operative and
      postoperative complications were noted. The patients were followed for a mean
      period of 17.7 months using the same parameters. RESULTS: The 22 patients with
      PHPT had a mean age of 76.3 +/- 5.9 years (range 70-88 years) and a female to
      male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n =
      15), hypertension (n = 22), non-insulin-dependent diabetes mellitus (n = 9),
      chronic obstructive pulmonary disease (n = 3), and previous neck surgery (n = 3).
      Mean preoperative serum calcium, phosphorous and PTH were 11.7 +/- 1.3 mg/dl, 2.5
      +/- 0.5 mg/dl and 160.9 +/- 75.4 pg/ml respectively. In 20 of the 22 patients,
      surgery was successful in curing PHPT (91%). One patient had persistent
      hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal
      accesss surgery) was successfully performed 2 weeks later. There were no
      complications and no morbidity postoperatively. Mean postoperative serum calcium,
      phosphorous and PTH were 9.6 +/- 1.2 mg/dl, 3.0 +/- 0.5 mg/dl and 35.2 +/- 24
      pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 +/
      1.3 mg/ml) after long-term follow-up (mean 17.7 +/- 9.6 months). CONCLUSIONS:
      Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma
      is a safe and effective method to cure hyperparathyroidism in the elderly.
      Success of surgery is directly related to the surgeon's experience and to the
      precise localization marking provided by sestamibi scintigraphic SPECT
      localization and concurrent sonographic findings.

PMID- 12811948
TI  - Saliva secretion and oral flora in prolonged nasogastric tube-fed elderly
      patients.
AB  - BACKGROUND: In a previous study we showed that prolonged nasogastric tube feeding
      is associated with pathogenic oral flora. OBJECTIVE: To reexamine the impact of
      prolonged nasogastric tube feeding on the oral microbiota and to explore the
      salivary flow and composition in elderly patients in long-term care. METHODS: We
      compared a group of elderly patients fed by nasogastric tube with a control group
      of elderly patients in long-term care who are fed orally. Bacteriologic studies
      were performed by culturing samples from the oropharynx. Saliva studies included
      quantitative and biochemical analysis of basal and stimulated salivary flow.
      RESULTS: Bacteriologic studies performed in 90 patients revealed a significantly
      higher prevalence of gram-negative bacteria in nasogastric tube-fed patients (73%
      vs. 13%, P < 0.001). It is emphasized that Pseudomonas aeruginosa and Klebsiella
      pneumoniae were commonly and exclusively isolated from the oral flora of the
      nasogastric tube-fed patients (P < 0.001, P < 0.05). In the saliva studies
      performed on 23 nasogastric tube-fed and 21 control patients, basal and
      stimulated salivary flow was not significantly different in the two groups,
      however the ratio of stimulated to basal flow was reduced in the nasogastric tube
      fed group (P < 0.05). Significant differences were also found in the
      concentrations of sodium, amylase, phosphor and magnesium. Noteworthy was the
      concentration of uric acid, the main non-enzymatic antioxidant of saliva, which
      was significantly lower in nasogastric-tube fed patients (P < 0.002).
      CONCLUSIONS: These findings suggest that prolonged nasogastric tube feeding is
      associated with pathologic colonization of the oroparynx and with alterations in
      the saliva that are related to the risk of aspiration pneumonia. Further research
      is called for, as well as a thorough revision of the existing oral cleansing
      procedures in these patients.

PMID- 12811949
TI  - Risk factors and characteristics of falls resulting in hip fracture in the
      elderly.
AB  - BACKGROUND: Risk factors for injurious falls among elderly people differ from
      those for falls in general. The characteristics of falls play an important role
      in determining the risk of hip fracture. OBJECTIVE: To investigate the risk
      factors associated with the fall characteristics known to be associated with the
      majority of hip fractures, e.g., a lateral fall and a subsequent impact on the
      greater trochanter. METHODS: In this 6 month prospective observational case
      control study, 101 individuals aged 65 years and over hospitalized following a
      hip fracture were interviewed 7-14 days after the accident. Data were also
      obtained from medical records, focusing on known predisposing and situational
      risk factors for the fall. We compared the risk factors between two groups:
      patients who suffered a lateral fall and subsequent impact on the greater
      trochanter of the femur, and patients who suffered other types of falls. RESULTS:
      Only 51.5% of the hip fracture patients reported that they had fallen directly to
      the side. Apart from age, there were no significant differences between the
      groups in other factors studied. When considering both fall direction and the
      area that took the main impact, we found that the majority of patients (85%)
      reported having fallen onto the posterolateral aspect and/or a fall with an
      impact on the greater trochanter. CONCLUSION: Our findings did not show
      differences (except for age) in the factors studied between the groups. This
      study suggests that both fall direction and the area that takes the main impact
      should be considered in the characteristics of falls that might cause a hip
      fracture. Characteristics associated with greatest fracture risk include a fall
      onto the posterolateral aspect and/or a fall with an impact on the greater
      trochanter. More studies are needed to evaluate potential risk factors associated
      with this type of injury.

PMID- 12811950
TI  - Effect of correction of anemia with erythropoietin and intravenous iron in
      resistant heart failure in octogenarians.
AB  - BACKGROUND: Congestive heart failure is extremely common in octogenarians and is
      associated with severe fatigue, shortness of breath, recurrent hospitalizations,
      and death. These patients, many of whom are anemic, are often resistant to
      standard CHF therapy including angiotensin-converting enzyme inhibitors, beta
      blockers and diuretics. OBJECTIVES: To examine whether correction of the anemia
      (hemoglobin < 12 g/dl) in CHF patients can improve their clinical condition.
      METHODS: Forty octogenarians with anemia and severe resistant CHF were
      administered a combination of subcutaneous erythropoietin and intravenous iron
      sucrose. RESULTS: This combination therapy led to a marked improvement in cardiac
      function, shortness of breath and fatigue, a marked reduction in the rate of
      hospitalization and a stabilizing of renal function. CONCLUSION: Anemia appears
      to be an important but ignored contributor to the progression of CHF, and its
      correction may improve cardiac and renal status as well as the quality of life in
      elderly patients.

PMID- 12811951
TI  - Gender-associated findings in postmortem examinations of elderly patients: an
      increased rate of pulmonary embolism in women.
AB  - BACKGROUND: While age at death is on the rise, the number of postmortem
      examinations is declining and is disproportionately low among the elderly
      population. Research on, the subject of gender-associated pathology in the
      elderly is also scarce. OBJECTIVE: To seek eventual gender-related differences in
      autopsies of elderly patients. METHODS: We analyzed the data extracted from a
      published report on 93 PMEs performed at a geriatric hospital during the past 20
      years. RESULTS: Ninety-three autopsies, representing 1.2% of the 8,101 deaths
      during these 20 years, were performed. Forty-five of the deceased were women and
      48 were men. The incidence of pulmonary embolism was significantly higher in
      women (28%) than in men (10%) (P < 0.02). There was no significant difference in
      the gender distribution of the other diagnoses. CONCLUSION: Gender distribution
      of PME-based causes of death in elderly patients revealed a significant rate of
      pulmonary embolism in women. A thorough search of the medical literature revealed
      two previous studies with similar findings. Further research will determine
      whether pulmonary embolism is more frequent or whether it has a worse prognosis
      in frail elderly women.

PMID- 12811952
TI  - Care of acute stroke patients in general hospitals in Israel.
AB  - BACKGROUND: An important question on the health agenda concerns the most
      appropriate place to hospitalize stroke patients and its effect on acute stroke
      care. OBJECTIVES: To examine how the existing hospital system treats these
      patients, specifically: a) the departments to which stroke patients are admitted;
      b) differences in the admission, diagnosis and rehabilitative care of stroke
      patients, by department,' c) patient characteristics, by department; and d)
      mortality rates during hospitalization. METHODS: We surveyed 616 people with
      acute stroke (ICD-CM9 430-433, 436) admitted consecutively to one of seven large
      general hospitals in Israel between October 1998 and January 1999. Data were
      collected from medical records at admission and at discharge. RESULTS: Forty-two
      percent of the patients were admitted to an internal medicine department, 56% to
      a neurology department, and only 2% to a geriatric department. The majority (95%)
      underwent a computed tomography scan of the brain, but other imaging tests were
      performed on fewer patients, with significant differences among hospitals and
      between internal medicine and neurology departments. Patients admitted to
      neurology departments were younger and had milder stroke symptoms than did
      patients admitted to internal medicine departments. Fifty-three percent of
      patients received at least one type of rehabilitative care during their hospital
      stay--usually physiotherapy, and least often occupational therapy. Seventeen
      percent of stroke patients died during hospitalization. Mortality was not found
      to be related to the admitting department. CONCLUSIONS: Uniform realistic
      policies and work procedures should be formulated for all hospitals in Israel
      regarding the admitting department and processes as well as the performance of
      diagnostic imaging. Standards of medical and rehabilitative care and discharge
      destination should be developed to promote quality of care while containing
      utilization and costs.

PMID- 12811953
TI  - Patterns of drug use among the community-dwelling old-old population in Israel.
AB  - BACKGROUND: Due to multiple chronic illness and disability, the elderly consume a
      disproportionately large share of medications. OBJECTIVES: To assess the patterns
      and determinants of drug use among the community dwelling old-old population.
      METHODS: The study population included 1,369 old-old persons from the baseline
      data of the Cross-Sectional and Longitudinal Aging Study (CALAS), which is based
      on a national random stratified sample of the Israeli Jewish population aged 75
      94 years. RESULTS: The mean number of drugs used by the study population was 3.3,
      and only 12.5% did not consume any drugs, Multivariate linear regression analysis
      showed that women used significantly more drugs than men, and that those born in
      Europe took significantly more drugs than those born in Israel and Asia-Africa.
      The number of medical conditions was the strongest predictor of drug use.
      Hospitalizations during the last year and frequent visits to family physician
      were also significant factors related to drug use. All variables combined
      explained 40% of the variance in drug use by the old-old. The most commonly used
      therapeutic groups were cardiovascular drugs (53%), psychotropic drugs (31%),
      analgesics (30%), and gastrointestinal drugs (28%). CONCLUSIONS: Our data
      indicate that in addition to the association of drug use with health status and
      healthcare utilization, the number and type of drugs taken vary with gender and
      place of birth.

PMID- 12811954
TI  - The use of accepted preventive medicine practice among elderly patients in
      community clinics in the Jerusalem area.
AB  - BACKGROUND: With the aging of the population and the increase in the number of
      elderly patients under the care of primary care physicians in the community, it
      is essential that the physician be aware of the preventive medicine
      recommendations for this group of patients. Accepted evidence-based guidelines
      have been developed for the older patient and adherence to these guidelines may
      play a significant role in decreasing morbidity and mortality in the elderly.
      OBJECTIVES: To determine whether elderly patients in community clinics are aware
      of the preventive medicine practices that are relevant and available to them, and
      to assess which factors influence their decision to use such interventions. Of
      particular interest was to evaluate the role of the doctor-patient relationship
      on the degree of patient compliance with preventive procedures. METHODS: Patients
      attending community clinics of the Clalit Health Services in Jerusalem were
      interviewed. Background information was obtained and the patients were questioned
      regarding the use of the following preventive medicine recommendations: screening
      for occult blood in the stool, testing of vision and hearing, influenza and
      pneumococcal immunization, thyroid-stimulating hormone testing, digital rectal
      examination for prostate cancer, and calcium supplementation. The patients were
      questioned regarding the use of aspirin or oral anticoagulation where relevant.
      Factors influencing their level of compliance were examined. RESULTS: The study
      group comprised 205 patients with an average age of 74.5 years. Overall the rates
      of compliance were high, with 78% undergoing visual assessment, 87% fecal occult
      blood testing, and 81% influenza immunization. Pneumococcal immunization had been
      administered to 49% of those interviewed and 56% had their hearing tested.
      Digital rectal examination had been performed in 45% of patients. Calcium
      supplementation was used in 60% of patients. Almost all the patients (91-100%)
      noted that the physician had initiated the procedure and that non-compliance was
      due to patient preferences. Of the 172 patients who were assumed to benefit from
      aspirin use, 153 (89%) used the medication, and 87% of 23 patients with atrial
      fibrillation were on chronic anticoagulation. CONCLUSIONS: A high level of
      compliance with preventive medicine recommendations was found among this group of
      elderly patients. The doctor-patient relationship had a positive effect on the
      patients' compliance.

PMID- 12811955
TI  - Postgraduate diploma courses in geriatric psychiatry.
AB  - BACKGROUND: Training in geriatric psychiatry constitutes a fundamental element
      toward further development of this relatively new branch of medicine. However, it
      varies both in quantity and quality among different countries, healthcare
      providers and medical schools. OBJECTIVES: To describe the demographic and
      professional characteristics of participants in postgraduate diploma courses in
      geriatric psychiatry, and the perceived contribution of the courses, and to
      compare these variables among the participants in 1 year and 3 year courses, and
      between psychiatrists and non-psychiatrists. METHODS: A retrospective self
      administered questionnaire was mailed to the 153 physicians who participated in
      the two courses. The 60 questionnaires completed and returned were analyzed.
      RESULTS: Participants in the courses constituted a heterogenous group in terms of
      demographic and professional characteristics, with no differences between 1 year
      and 3 year course participants, or between psychiatrists vs. non-psychiatrists
      (with the exception of more involvement of non-psychiatrists and 1 year course
      participants in old-age homes). Most responders indicated both the theoretical
      and practical benefits and application to daily practice of the material learned.
      Similarly, most responders indicated that after the courses they definitely used
      general assessment scales to a much greater extent, particularly cognitive
      scales, as well as operational diagnostic criteria for dementia. Participants in
      the 3 year course reported more significant use of assessment scales compared
      with 1 year participants, and 3 year participants and psychiatrists used the
      cognitive scales more often. There were no other significant differences between
      1 year and 3 year participants and between psychiatrists' and non-psychiatrists'
      reports regarding general and more specific contributions of the courses.
      CONCLUSION: Postgraduate diploma courses in geriatric psychiatry seem to have a
      favorable effect on participants, irrespective of course duration or specialty.
      However, course duration positively influenced the implementation of assessment
      scales in general, and cognitive scales in particular. A prospective comparative
      study on this subject is warranted, with stricter definitions of participants'
      pre-course and postcourse background, attitudes, knowledge and benefits.

PMID- 12811956
TI  - Geriatric medicine in the 21st century.

PMID- 12811957
TI  - Potential applications of matrix metalloproteinase inhibitors in geriatric
      practice.
AB  - Matrix metalloproteinases are a family of enzymes that degrade different
      components of extracellular matrix. They play an important role in normal
      physiologic processes of maintaining tissue integrity and remodeling, as in wound
      healing, processes of development, and regeneration. However, excessive
      expression of MMP has been observed in many disease states, including rheumatoid
      arthritis and osteoarthritis, vascular remodeling in atherosclerosis and aortic
      aneurysm formation, neoplastic processes, macular degeneration and many others.

PMID- 12811958
TI  - Assessment tools for nutritional status in the elderly.
AB  - Nutritional assessment in the elderly consists of many different tests--clinical,
      biochemical and anthropometric. However, objective markers of nutritional
      assessment often do not reflect physiologic, physical, cognitive and emotional
      function. Moreover, nutritional assessment using objective markers is more
      complicated in the older subject because metabolic changes, among others, affect
      some of the routine biochemical test results, and the reference values of the
      anthropometric measures are not always age-adjusted. In addition, it is possible
      that functional impairment may occur at a subclinical level and precede a
      measurable alteration in body composition, i.e., there may be clearly defined
      alterations in muscle function at a time when significant changes in body
      composition could not be detected. Malnutrition or nutritional deficiency is a
      continuum that starts with an individual's inadequate intake (that, in fact, does
      not meet his or her needs) and progresses through a series of functional changes
      that precede any changes in body composition. At present there is no gold
      standard for evaluating nutritional status. The relationship between nutritional
      status and functional capacities apparently is the simplest, but also the most
      reliable index of malnutrition. The extent of dependency and disability has a
      considerable impact on nutritional status and vice versa.

PMID- 12811959
TI  - Antioxidants and healthy aging.
AB  - Although the free radical theory of aging is widely accepted among scientists,
      the possibility of using antioxidants to delay the aging processes seems to
      encounter considerable skeptism among clinicians. This may be due, at least in
      part, to lack of knowledge about the basic chemistry and biological behavior of
      oxidative stress, antioxidants, and the complex interactions between them.
      However, one cannot ignore the explosive growth of information concerning the
      mechanisms underlying the processes of aging, their consequences, and the use of
      antioxidants in suppressing such effects. In order to provide patients with the
      most accurate information regarding the use of antioxidant supplementation in
      their diet, it is important to obtain basic data regarding oxidative stress and
      antioxidants. This article explores the role of oxidative stress in the aging
      phenomena, recent evidence supporting supplementation of antioxidants for aged
      people, the ability of antioxidants to prevent or retard cancer and
      atherosclerosis (the major causes of mortality in the aged population), and the
      ability of antioxidant supplementation to delay age-dependent deterioration of
      cognitive function. Based on the data presented, we conclude that current
      knowledge provides insufficient and inconclusive support for antioxidant
      supplementation as a means of delaying aging processes, despite the encouraging
      results obtained in many studies.

PMID- 12811960
TI  - Comprehensive geriatric assessment: lessons in progress.

PMID- 12811961
TI  - The challenges of success: the aging of Israeli society.
AB  - In 2001 the number of residents aged 65 and over in Israel was 639,000, or 10% of
      the population. The rate of increase of the elderly population is twice that of
      the general population, thus the predicted number of elderly for 2020 is around
      1,025,000, representing a 60% increase. While this process is determined by a
      decline in both fertility and mortality, in Israel, immigration has also been a
      central factor in the process of aging. Life expectancy stands at 76.7 for men
      and 80.9 for women; at age 65 it is 16.4 years for men and 18.5 for women. The
      major factor influencing the increase in life expectancy during the past two
      decades has been the prevention of death among older people. Population aging, or
      "the demographic transition," also represents an "epidemiological transition"-
      from high rates of infectious and communicable diseases to high rates of chronic
      diseases among older people. During the past two decades, the number of disabled
      elderly has increased more than 2.5 times. In 2001, there were about 97,400
      disabled elderly in Israel, constituting about 15% of all elderly. By the year
      2010, the number of disabled elderly is expected to reach 120,100. The rate of
      increase of the disabled elderly population is almost double that of the total
      elderly population due to changes in this population's composition. However,
      recent research indicates that new cohorts of elderly are healthier than earlier
      cohorts but experience a decline in health at older ages. While advances in
      standard of living, medicine and technology have made this possible, a greater
      allocation of resources is required to prevent disability and maintain the
      quality of life.

PMID- 12811962
TI  - A framework for evidence-based geriatric prevention in Israel.

PMID- 12811963
TI  - The aging of Israel's Arab population: needs, existing responses, and dilemmas in
      the development of services for a society in transition.
AB  - The Arab population of Israel is relatively young. However, a significant
      increase is expected in the number of elderly Arabs in the coming years. At the
      end of 2001 there were 38,500 Arab elderly, but their number is expected to reach
      92,100 by 2020. This will represent a nearly 2.5-fold increase in absolute
      numbers. As the population ages, the number and percentage of people with chronic
      diseases and related disabilities will rise significantly. While the Arab elderly
      are much younger than the Jewish elderly, they are more disabled and therefore
      have greater medical and nursing needs. An extremely important measure of the
      need for formal services is an elderly person's functional ability, especially
      the ability to live independently. The percentage of Arab elderly who are
      disabled and need help with activities of daily living is twice as high as that
      of the Jewish elderly population. At present, 30% of the Arab elderly (39% of the
      women and 20% of the men), compared to 14% of Jewish elderly (17% of the women
      and 11% of the men), need help in at least one ADL (bathing, dressing, eating,
      mobility in the home, rising and sitting, getting in and out of bed). Concomitant
      with demographic changes are forces that affect the ability of informal support
      systems to provide care. For example, the rising number of Arab women in the
      labor force together with changes in elderly peoples' living arrangements have
      increased the need for formal services to share responsibility for the elderly
      with families. As services are developed, questions arise regarding the extent to
      which they have been adapted to the culture and norms of Arab society and meet
      that society's unique needs. This paper elaborates on some of these issues.

PMID- 12811964
TI  - Galantamine.

PMID- 12811965
TI  - A common presentation of an uncommon disease--systemic mast cell disease.

PMID- 12811966
TI  - "Asymptomatic" intestinal malrotation.

PMID- 12811967
TI  - [Schizophrenia and diabetes mellitus: not an improbable combination].
AB  - Three male schizophrenia patients, aged 41, 40 and 61 years respectively, who had
      undergone treatment without a satisfactory result, were treated with the
      antipsychotic clozapine. Diabetes mellitus developed within a period of several
      months to several years. The antipsychotic medication could be continued once the
      patients had been started on blood-glucose lowering medication. There seems to be
      an increased incidence of type-2 diabetes mellitus in patients with
      schizophrenia. It has been suggested that treatment with neuroleptics, especially
      atypical neuroleptics, provokes the onset of diabetes mellitus. The relatively
      young age (often < 50 years) at onset is a cause for concern. From a
      pathophysiological viewpoint, an increased prevalence of diabetic risk factors
      has been suggested for schizophrenia in addition to the toxic effect of
      neuroleptics in general. The possible consequences for the general health of this
      vulnerable group of patients warrant recommendations concerning the regular
      monitoring of these patients during treatment.

PMID- 12811968
TI  - [Nutrition and health--hypertension].
AB  - Hypertension, defined as a blood pressure > or = 140/90 mmHg upon repeated
      measurement or the use of antihypertensive medication, is present in 14% of Dutch
      adults. A healthy diet plays an important role in both the prevention and
      treatment of hypertension. Under controlled conditions, very good results have
      been obtained with the 'Dietary approaches to stop hypertension' (DASH)
      combination diet, which has recently been developed in the United States. The
      DASH combination diet contains large amounts of fruit, vegetables, fish and nuts,
      low-fat dairy products and reduced levels of total and saturated fat. This
      dietary pattern yielded blood pressure reductions of 11.4/5.5 mmHg in mildly
      hypertensive patients. Intervention studies have shown a favourable effect of
      salt reduction on blood pressure in hypertensive patients, even in the case of
      mild hypertension. Simultaneous increases in potassium and magnesium intake could
      have an additional beneficial effect. The use of a low-sodium, high-potassium
      mineral salt could make a useful contribution to the prevention and treatment of
      hypertension. In case of hypertension, it is further recommended to reduce the
      intake of liquorice to less than 50 g per day. These dietary measures, combined
      with weight loss and physical exercise, may prevent drug treatment in patients
      with mild hypertension.

PMID- 12811969
TI  - [Diagnosis of cystic fibrosis; simple genotyping to rule out the disease
      preferable to starting with the sweat test].
AB  - For historical reasons, the sweat test remains the cornerstone in the diagnostic
      work-up for cystic fibrosis (CF). If CF is suspected, the sweat test (following
      pilocarpine iontophoresis) is usually performed first to confirm or rule out the
      diagnosis of CF. Sweat testing, however, is cumbersome to the patient, prone to
      technical difficulties and unreliable in young children < 4 weeks as well as in
      adults because of increasing chloride concentrations with age. False-positive and
      false-negative results do exist. Simple DNA testing with PCR in peripheral blood
      for a small number of the most common mutations causing CF, notably the delta
      F508-mutation in the Dutch population, rules out CF with a likelihood of more
      than 99%. Because of the high negative predictive value of DNA testing, in
      combination with its speed, reliability and convenience for the patient, starting
      the diagnostic work-up for CF with DNA testing can be justified in hospitals
      which possess the laboratory facilities for this type of test.

PMID- 12811970
TI  - [Undertreatment of depression; causes and recommendations].
AB  - Efficacious forms of treatment for depression are available, but too many people
      suffering from depression are either treated inadequately or not at all. This
      undertreatment may play a role in the failure to reduce in the prevalence of
      depression. Possible causes of undertreatment include delayed help-seeking,
      delayed treatment, non-compliance, mediocre self-care and inappropriate
      treatment. Furthermore, the treatment culture is insufficiently population-based
      and proactive, and the chronic-recurrent nature of many depressions is too often
      neglected. Both the content and organisation of mental health care, in primary
      care and speciality services alike, should explicitly target reduction of the
      prevalence of depression in the population, in particular by trying to narrow the
      gap between the 'efficacy' and 'effectiveness' of treatment modalities. Important
      elements in this approach include 'individualized stepped care' models,
      implementation of optimal care by means of care programs, redefinition of the
      roles of care-provider and patient (greater emphasis on partnership) and
      abolition of the distinction between somatic health care and mental health care.

PMID- 12811971
TI  - [From gene to disease; CD40 ligand deficiency as the cause of X-linked hyper-IgM
      syndrome].
AB  - X-linked hyper-IgM syndrome (XHIM) is a rare congenital immunodeficiency
      disorder, characterised by a defect in both humoral and cellular immune
      responses. In XHIM, the membrane glycoprotein CD40 ligand (expressed on activated
      T-cells) is deficient, which compromises T-cell interactions with antigen
      presenting cells. Patients with XHIM present with severe, recurrent infections,
      predominantly of the respiratory and gastrointestinal tract. The gene encoding
      the CD40 ligand is located on the long arm of the X chromosome.

PMID- 12811972
TI  - [Diagnostic image (140) A woman suffering from leg thrombosis. Retroperitoneal
      fibrosis].
AB  - A 64-year-old woman presented with thrombosis of the iliac veins and the inferior
      caval vein. CT revealed retroperitoneal fibrosis as a probable cause.

PMID- 12811973
TI  - [Intensive care medicine in the Netherlands, 1997-2001. I. Patient population and
      treatment outcome].
AB  - OBJECTIVE: To describe the patients admitted to intensive care units (ICUs) in
      the Netherlands between 1997-2001 and the treatment outcome. DESIGN: Descriptive.
      METHOD: For the years 1997-2001, prospective admission and discharge data as well
      as all data necessary for calculating prospective severity of illness scores
      (e.g. APACHE II and SAPS II) were collected for all patients that were admitted
      to 18 ICUs participating in the Dutch National Intensive Care Evaluation (NICE).
      Outcome measures were ICU mortality and hospital mortality, length of hospital
      and ICU admission, and standardised mortality ratio (SMR). RESULTS: Data from
      55,016 admissions were registered. The median APACHE II score was 15 (P25-P75: 10
      20) and the median SAPS II score was 29 (19-43). The median ICU length of
      admission for individual ICUs varied between 0.86 and 2.76 days. The occupied ICU
      capacity of individual ICUs varied between 220 and 1260 days per 100 patients
      admitted for non-cardiosurgical patients and between 110 and 330 days per 100
      patients admitted for cardiosurgical patients. The ICU mortality and hospital
      mortality were 9.0% and 12.9% respectively. The mean SMR according to APACHE II
      was 0.95 (95% CI: 0.93-0.98). The SMR of the individual participating hospitals
      varied between 0.55 (95% CI: 0.37-0.80) and 1.20 (1.13-1.28). CONCLUSION:
      Hospital mortality for ICU-admitted patients in the NICE registration was 12.9%.
      For patients who could be evaluated with the APACHE II model, actual hospital
      mortality was lower than predicted by this model. Significant differences in
      length of admission, hospital mortality and SMR were found between individual
      hospitals.

PMID- 12811974
TI  - [Intensive care medicine in the Netherlands, 1997-2001. II. Changes over time and
      differences between hospitals].
AB  - OBJECTIVE: To describe efficacy (mortality) and efficiency (length of admission)
      of intensive care (IC) treatment after admission due to a prior cardiothoracic
      operation or pneumonia, based on data from the Dutch National Intensive Care
      Evaluation (NICE) foundation. DESIGN: Descriptive. METHOD: Data for the period 1
      January 1997-31 December 2001 were extracted from the NICE databank for patients
      admitted after cardiothoracic surgery and for patients admitted with pneumonia.
      The variables changes in time, risk factors for mortality, and differences
      between hospitals were analysed. RESULTS: There were 25,463 admissions to 5
      hospitals following cardiothoracic surgery and 1408 admissions to 18 hospitals
      due to pneumonia. An increase in valve surgery was noted in the cardiothoracic
      surgery group: from about 10% to about 25%. In the group undergoing valve
      operations, there was an increase in the average age of the patients and in the
      number of patients with comorbidity. No significant differences in mortality
      between hospitals were detected. However, the length of ICU treatment differed.
      Hospital mortality in the pneumonia group was 33.9%. Differences between
      hospitals with respect to mortality (both crude mortality and severity-of-illness
      adjusted mortality) and length of ICU admission were found. CONCLUSION: With the
      NICE registration it is possible to detect differences and trends. This is a
      valuable tool for indicating where and how quality and efficiency in intensive
      care medicine can be improved.

PMID- 12811975
TI  - [Two children with severe recurrent infections and the X-linked hyper-IgM
      syndrome].
AB  - A boy suffered from severe recurrent intestinal infections from the age of 8
      months onwards; investigation into an immune disorder ultimately resulted in the
      diagnosis of 'hyper-IgM syndrome'. He was treated successfully with bone marrow
      transplantation, using an HLA-matched donor. Another boy had severe recurrent
      respiratory tract infections from the age of 3 months onwards. At the age of 6.5
      years, 'hyper-IgM syndrome' was diagnosed. No suitable donor was available. In
      addition, he developed sclerosing cholangitis and end-stage liver disease, making
      a combined bone marrow and liver transplantation too risky. He died at 10.5 years
      of age. X-linked hyper-IgM syndrome is a rare congenital immunodeficiency
      disorder, characterised by a defect in both humoral and cellular immune
      responses. Deficiency in the membrane glycoprotein CD40 ligand (expressed on
      activated T-cells) compromises T-cell interactions with antigen-presenting cells.
      In a child with severe recurrent infections, and with dysgammaglobulinaemia with
      a normal or increased IgM level, the diagnosis of 'X-linked hyper-IgM syndrome'
      should be considered.

PMID- 12811976
TI  - [Obstacles to the routine discussion with hospital patients of possible
      cardiopulmonary resuscitation].

PMID- 12811977
TI  - [Too young for a twisted painful back].

PMID- 12811978
TI  - [The Dutch College of General Practitioners' practice guideline 'Delirium in
      elderly people'; response from a psychiatric perspective].

PMID- 12811979
TI  - [Summary of the Dutch College of General Practitioners' practice guideline
      'Diagnosis of breast cancer'].

PMID- 12811980
TI  - More about after-hours care.

PMID- 12811981
TI  - Travel time: to pay or not to pay?

PMID- 12811983
TI  - Disputes between dentists over patient records.

PMID- 12811984
TI  - Dr. Ray Gist talks about Michigan dentistry. Interview by Michael G. Maihofer.

PMID- 12811985
TI  - "Give Kids a Smile" day helps thousands of Michigan children.

PMID- 12811986
TI  - A record-setting year for the MDA/Crest coloring contest.

PMID- 12811987
TI  - Are you blaming patients for your own mistakes?

PMID- 12811988
TI  - Neuropsychological study of familial Alzheimer's disease caused by mutation E280A
      in the presenilin 1 gene.
AB  - In Antioquia, Colombia, investigators have recently discovered the largest family
      with the E280A mutation in the presenilin 1 gene that causes one type of familial
      Alzheimer's disease (FAD). The current study compares two groups within this
      family: those diagnosed with Alzheimer's disease (AD) in its early stage (nine
      subjects) and relatives (carriers) who did not show any signs of dementia (nine
      subjects). A battery of the following neuropsychological tests was administered
      to subjects in both groups: the Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD), a Phonological Verbal Fluency test, the Visual "A"
      Cancellation Test, memory of three phrases, the Rey-Osterrieth Complex Figure,
      and the Trail Making Test Part A. Statistical analyses of the average test scores
      of each group showed that the AD group scored significantly (p < 0.01 or p <
      0.05) lower on 29 of the 43 neuropsychological variables measured (67 percent).
      Therefore, this specific battery was useful in discriminating subjects with AD
      from their healthy relatives who are carriers of the disease. The AD group as a
      whole presented slight dementia with predominant deficits in memory, language,
      praxis, and attention. This profile is similar to those reported in subjects with
      sporadic AD in its early stage and confirms the findings found in other
      neuropsychological studies of subjects with FAD linked to mutations in chromosome
      14.

PMID- 12811989
TI  - Disruptive vocalizations: a means to communicate in dementia?
AB  - Disruptive vocalizations (DVs) constitute a serious problem in geriatric nursing
      homes. The current literature suggests that DV can be interpreted as a way for
      demented persons with language limitations to communicate with others. In an
      attempt to test this hypothesis, 59 participants were recruited from six nursing
      homes to form two groups: one group of individuals with preserved language skills
      (PLS) and another group with altered language skills (ALS). They were compared on
      the frequency and types of DV. The results indicate that individuals with ALS
      manifest DV at a greater frequency than those with PLS. These persons also
      present a greater number of distinct DV forms. The results are interpreted in
      terms of language deterioration associated with dementia.

PMID- 12811990
TI  - Voices from the margin: the nurse aide's role in pain management of
      institutionalized elders.
AB  - The training and function of Certified Nurse Aides (CNAs) has traditionally
      focused on safe, hygienic, direct care and concrete, practical task completion.
      These two basic premises have directed training and job criteria and have evolved
      without much regard for the personal opinions, desires, and thoughts of the nurse
      aides themselves. However, CNA roles are expanding and changing daily, and what
      this expansion means in terms of patient care has ever-increasing relevance. How
      and what CNAs think and feel about their role and their training, and how both
      could be improved to meet the needs of patients and the demands of the healthcare
      system, are of vital interest to all those who rely upon their expertise.

PMID- 12811991
TI  - Student-led exercise sessions yield significant fitness gains for Alzheimer's
      patients.
AB  - At a time when they are losing skills in virtually all arenas of life, persons
      with Alzheimer's disease can experience significant, esteem-building achievements
      in physical fitness and mood through supervised participation in an exercise
      program. The effects of physical exercise plus cognitive and social stimulation
      on persons with early stage Alzheimer's disease were assessed in a longitudinal
      study. Twenty-four such individuals, aged 54 to 88 at program entry, participated
      in 16 to 20 exercise sessions and 10 community activity sessions per semester for
      two to eight semesters. Half of the weekly exercise sessions included memory and
      language stimulation activities. Students, supplemented by family caregivers,
      supervised the sessions. Exercise sessions consisted of flexibility, balance,
      aerobic, and weight resistance activities. Preparticipation and semiannual post
      testing of aerobic fitness and duration and upper and lower body strength was
      done. Highly significant fitness gains (p < .001) were achieved in the six-minute
      walk test, upper and lower body strength, and duration of aerobic exercise. Five
      participants, aged 86 to 91, completed six to eight semesters and were doing 27
      to 45 minutes of aerobics per session at program's end. Five participants scored
      within the normal range for age-matched healthy active adults on the six-minute
      walk test at baseline. Nine others achieved and three exceeded the normal range
      during treatment. Cognitive decline was slowed and mood improved. First-year
      cognitive outcomes have been published elsewhere. An article reporting final
      cognitive outcomes is in preparation; Outcome data is summarized on the project
      website: www.u.arizona.edu/ ~sarkin/elderrehab.html. The benefits of physical
      exercise can be made available at nominal cost to Alzheimer's patients and other
      elderly persons by using students to provide transportation, supervision, and the
      motivational support that is key to exercise adherence. Further research is
      needed to determine the relative contributions of each program component to the
      positive outcomes.

PMID- 12811992
TI  - Creutzfeldt-Jakob disease: two case studies.
AB  - Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, neurodegenerative
      disorder causing dramatic neuromuscular symptoms, profound dementia, and death.
      In this article, the epidemiology, etiology, modes of transmission, clinical
      manifestations, determination of possible/probable CJD diagnosis in life, and the
      postmortem neuropathology of definite CJD are discussed in depth. Case studies of
      two individuals, each affected by different subtypes of sporadic Creutzfeldt
      Jakob disease (sCJD), are presented, along with a discussion of the many
      challenging nursing and psychosocial issues surrounding the supportive care of
      these individuals and families in life and death.

PMID- 12811993
TI  - The relation between the perceived role of family and the behavior of the person
      with dementia.
AB  - The purpose of this study was to investigate the relation between the perceived
      role of family and the behavior of the person with dementia in a sample of older
      adults. Two instruments were used in data collection: The Family Perceptions of
      Caregiving Role (FPCR) and the Cohen-Mansfield Agitation Inventory (CMAI). A
      total of 40 persons with dementia were included in the study. Each had a family
      respondent and a nurse respondent. The data analyses produced three major
      findings. First, it was revealed that there was no significant difference between
      agitation levels of persons with dementia who received more frequent family
      visits and those who did not. Second, the study revealed that family caregivers
      did not perceive a partnering relationship with staff. Finally, correlational
      analysis provided little evidence of a link between the family's perceived role
      in partnering and the behavior of the person with dementia, specifically in
      relation to agitation levels. Although no significant relation was established
      between the family's perceived role in partnering and the behavior of the person
      with dementia, there was high family and caregiver satisfaction. The clearest
      element of the family's perspective was the desire that staff members care about
      the individual with dementia as a person.

PMID- 12811994
TI  - Scenes of Lee, Part Three.

PMID- 12811995
TI  - Cops and nurses.  Partnership for safety.

PMID- 12811996
TI  - Reactions to patient suicide.

PMID- 12812001
TI  - Treating treatment-resistant depression. Whether to switch, augment, or combine
      therapies.

PMID- 12812002
TI  - Eye movement desensitization and reprocessing. A brief and effective treatment
      for stress.
AB  - 1. Eye movement desensitization and reprocessing (EMDR) is an integrative therapy
      that "unlocks" disturbing memories or beliefs and reprocessess them, in some way,
      so they are no longer as disabling. 2. EMDR can be used for any experientially
      based psychological problems and has proven especially effective for traumatic
      imagery associated with posttraumatic stress disorder. 3. A primary benefit of
      EMDR is its time efficiency, requiring as few as 3 to 5 hours of treatment. 4.
      Many potential mechanisms (i.e., cognitive, hypnotic, self-disclosure,
      biological) may account for the effectiveness of EMDR.

PMID- 12812003
TI  - Providers' perceptions of how rural consumers access and use mental health
      services.
AB  - This article describes the third phase of a research study undertaken within a
      Canadian provincial regional health authority to explore and analyze mental
      health services and other resources used by rural consumers after discharge from
      inpatient mental health programs. The focus of this article is the qualitative
      research findings obtained from mental health service providers and members of
      allied agencies. This article will discuss the literature on rural consumers'
      access and use of mental health programs and services; describe the context and
      method used to conduct the focus groups with rural service providers;
      characterize access and use problems from the service providers' perspectives;
      and suggest strategies to address these problems.

PMID- 12812004
TI  - Healing broken hearts.
AB  - 1. Posttraumatic stress disorder, anxiety, and depression have a significant
      negative effect on the physical functioning of individuals with coronary artery
      disease. 2. A diagnosis of major depression is recognized to be an independent
      risk factor for cardiac events. 3. Preoperative and postoperative interventions
      can increase individuals' compliance with cardiac and psychiatric self-care after
      discharge.

PMID- 12812005
TI  - Journal's policy regarding conflict of interest.

PMID- 12812006
TI  - Biases affecting the proportional reporting ratio (PPR) in spontaneous reports
      pharmacovigilance databases: the example of sertindole.
AB  - BACKGROUND: Automated measures of reporting disproportionality in databases of
      spontaneous reports of adverse drug reactions are an emerging tool to identify
      drug-related alerts. Sertindole, a new atypical neuroleptic known to prolong the
      QT interval, was suspended in November 1998 because the proportion of reports of
      fatal reactions suggesting arrhythmia among all reports with sertindole was
      almost ten times higher than that for other atypical neuroleptics in the UK. This
      excess risk was not predicted in preclinical data and had not been found in
      premarketing trials. METHOD: Reporting patterns over time were analysed.
      Prescription Event Monitoring (PEM) studies and a large retrospective cohort
      allowed for the comparison of actual death rates with atypical neuroleptics, and
      to assess which proportion of the deaths that occurred were reported. RESULTS:
      There were indications of possible skewing of reporting related to notoriety,
      surveillance and market size effects. Death rates in PEM studies were essentially
      similar between sertindole and other neuroleptics. Cardiac deaths had been two to
      three times more often reported than other causes of death. CONCLUSION:
      Proportional reporting ratios indicate differential reporting of possible
      reactions, not necessarily differential occurrence. There was no indication of an
      actual increase of risk of all causes or cardiac deaths during sertindole
      treatment, but only an increased risk of its being reported. The suspension of
      sertindole was rescinded by Committee on Proprietary Medicinal Products (CPMP) in
      October 2001.

PMID- 12812007
TI  - Dealing with uncertainty in drug safety: lessons for the future from sertindole.

PMID- 12812008
TI  - 'Dear doctor...'--evaluating the impact of risk communication efforts.

PMID- 12812010
TI  - The liver and statin drug therapy: uncertain navigation in the sea of risk
      benefit.

PMID- 12812009
TI  - Impact of cisapride label changes on codispensing of contraindicated medications.
AB  - OBJECTIVE: To quantify the impact of the first three label changes and 'Dear
      Doctor' letters as sole interventions, sent to prescribers and pharmacists, on
      the prescribing and dispensing of cisapride and contraindicated drugs. METHODS:
      Using a managed care claims database, a total of 38,757 patients with cisapride
      prescriptions (July 1993-December 1998) were selected. An interrupted time series
      analysis and an exponentially weighted moving average analysis (EWMA) were
      conducted to determine whether there were changes in the proportion of
      contraindicated codispensing following each intervention. RESULTS: 3.6% of
      cisapride dispensing overlapped with contraindicated drug dispensing. Beginning
      in 1994, the overlapped proportions declined slowly from 4.5% ending at 3.2% in
      1998. The interrupted time series analysis showed that there was a statistically
      significant abrupt permanent decrease in the proportion of contraindicated
      dispensing following the June 1998 label change (coefficient -1.0094, p = 0.045),
      meaning that the proportion of contraindicated dispensing dropped nearly one
      percentage point after the third intervention. The 1995 label changes did not
      have statistically significant effects. The EWMA analysis showed that the
      proportion of contraindicated dispensing was lower than 3 standard deviations
      below average during the period after the June 1998 intervention, with no
      significant effects following the two earlier interventions. CONCLUSIONS: The
      June 1998 cisapride label change and accompanying 'Dear Doctor' letter had a
      downward impact on the proportion of dispensing of contraindicated drugs with
      cisapride. The other two label changes did not have independent significant
      impacts.

PMID- 12812011
TI  - Liver function testing in patients on HMG-CoA reductase inhibitors.
AB  - PURPOSE: The Food and Drug Administration currently requires the labeling of HMG
      CoA reductase inhibitors to recommend liver function tests (LFTs) before the
      start of therapy and at various intervals during therapy, depending on the
      specific agent. We sought to determine the frequency and patterns of LFT
      screening in patients receiving HMG-CoA reductase inhibitors. METHODS: A
      retrospective study was conducted at a staff-model health maintenance
      organization among 4178 new users of HMG-CoA reductase inhibitors during the
      period 1 January 1991 through 31 December 1996. The number and proportions of HMG
      CoA reductase inhibitor therapy courses with baseline LFTs (within 180 days prior
      to dispensing), follow-up LFTs and LFT abnormalities were calculated. RESULTS:
      For the initial HMG-CoA reductase inhibitor dispensed, 1947 patients (47%) had at
      least one screening LFT at baseline and 3063 (73%) had at least one follow-up
      LFT. Twenty-seven (0.9%) patients with at least one follow-up LFT performed had a
      level greater than 3 times the upper limit of normal. In a random sample of 100
      discontinued patients, none discontinued due to elevated LFTs or liver disease.
      CONCLUSIONS: A large proportion of patients dispensed HMG-CoA reductase
      inhibitors in this managed care setting did not have baseline and follow-up LFTs
      performed. Modest LFT abnormalities were common among users of HMG-CoA reductase
      inhibitors; however, in this population, serious abnormalities were rare.

PMID- 12812012
TI  - Prescription and non-prescription analgesic use among the US adult population:
      results from the third National Health and Nutrition Examination Survey (NHANES
      III).
AB  - PURPOSE: To estimate prescription and non-prescription analgesic use in a
      nationally representative sample of US adults. METHODS: Data collected during the
      third National Health and Nutrition Examination Survey (1988-1994), for persons
      17 years and older were analyzed (n = 20,050). During the household interview,
      respondents reported use, in the last month, of prescription and non-prescription
      analgesics. RESULTS: An estimated 147 million adults reported monthly analgesic
      use, Prescription analgesic use was 9% while non-prescription use was 76%.
      Females were more likely than males to use prescription (11 vs. 7%, p < 0.001)
      and non-prescription (81 vs. 71%, p < 0.001) analgesics. Across race-ethnicity
      groups, males (approximately 8%) and females (11-13%) had similar age-adjusted
      prescription analgesic use. Non-prescription analgesic use was higher among non
      Hispanic whites than non-Hispanic blacks and Mexican-Americans for males (76 vs.
      53% (p < 0.001) and 59% (p < 0.001), respectively) and females (85 vs. 68% (p <
      0.001) and 71% (p < 0.001), respectively). With increasing age, prescription
      analgesic use increased whereas non-prescription use decreased. Approximately 30%
      of adults used multiple analgesics during a 1-month period. This was more common
      among females (35%) than males (25%, p < 0.001) and among younger (17-44 years,
      33%) rather than older age groups (45+ years, 26%, p < 0.001). CONCLUSIONS:
      Analgesic use among US adults is extremely high, specifically of non-prescription
      analgesics. Given this, health care providers and consumers should be aware of
      potential adverse effects and monitor use closely.

PMID- 12812013
TI  - Trends in prescribing for heart failure in Dutch primary care from 1996 to 2000.
AB  - PURPOSE: The aim of this study is to explore trends in primary care prescribing
      for chronic heart failure (CHF) over a 5-year period (1996-2000). METHODS: This
      study consisted of repeated cross-sectional surveys in a dynamic cohort from the
      Integrated Primary Care Information (IPCI) primary care database. The cohort
      comprised all patients aged > or = 55 years with a CHF diagnosis and prescribed a
      cardiovascular medication during the study period. The point prevalence per
      calendar year was determined for each of the main drug groups used to treat CHF.
      RESULTS: The study population consisted of 3121 CHF patients. Small increases
      were seen in the percentage of CHF patients prescribed spironolactone (4.6%, 95%
      CI: 2.3-6.9%), beta-blockers (6.1%, 95% CI: 2.6-9.5%) and angiotensin II
      antagonists (6.8%, 95% CI: 5.1-8.6%) during the study period, while the
      prescribing of digoxin decreased (-4.4%, 95% CI: -8.2 to -0.7). Prescribing of
      diuretics (difference: -0.7% 95% CI: -2.7-4.2) and ACE inhibitors (difference:
      4.0% 95% CI: -0.1-8.2%) remained unchanged. CONCLUSIONS: Prescription of some
      drug groups for CHF increased. However, given the new scientific evidence that
      has emerged in past 15 years regarding CHF pharmacotherapy, the changes observed
      were less than expected.

PMID- 12812014
TI  - The Brighton Collaboration: enhancing comparability of vaccine safety data.

PMID- 12812015
TI  - Pharmacoepidemiology and drug safety.

PMID- 12812017
TI  - [Morbidity in recruits during basic military training].
AB  - The paper reviews morbidity of recruits during basic military training in
      Military training center in Sinj. The analysis comprised one generation of
      recruits (1/2000). Data had been collected from the protocol of health-care
      institution in Military training Center in Sinj. Acute respiratory infections
      make 50% of all reasons for contacting health-care professionals in Military
      training center. The importance of acute respiratory infections is ambiguous.
      They are the most frequent reason for absence from military training and they
      appear often and spread easily. Implementation of preventive measures is an
      unavoidable and obligatory part of job of every military unit physician, as well
      as of the commander of the unit.

PMID- 12812016
TI  - [Recirculation of urea and dialysis efficiency using dual-lumen dialysis
      catheters in various locations: may the venous lumen of the catheter be used as
      the arterial lumen and vice versa?].
AB  - AIM: To measure percentage of urea recirculation in hemodialysis by a dual-lumen
      central venous catheters of various localisations (e.g. jugular, subclavian and
      femoral), and also in cases when the venous lumen of the catheter is used as
      arterial lumen, and vice versa, and under these conditions to evaluate the
      efficiency of hemodialysis based on the measurements of urea reduction ratio.
      METHODS: Percentage of urea recirculation was measured in the patients with acute
      and chronic renal failure who underwent hemodialysis by a temporary dual-lumen
      central venous catheter of different localisations (jugular n = 16, subclavian n
      = 20, femoral n = 20). The measurements were done in cases when arterial line was
      connected to arterial lumen of the catheter, and venous line to the venous lumen
      of the catheter (correct connection = RI), and vice versa, i.e., when arterial
      line was connected to venous lumen of the catheter, and venous line was connected
      to arterial lumen of the catheter (reversed connection = R2). The efficiency of
      hemodialysis was evaluated by measuring urea reduction ratio in cases with the
      reversed (R2) connection. RESULTS: Statistically significant differences were
      found between R1 and R2 for jugular catheters (R1 = 2.38 +/- 1.09%, R2 = 7.59 +/-
      1.42%, n = 16, p = 0), for subclavian catheters (R1 = 3.03 +/- 3.15%, R2 = 15.8
      +/- 7.18, n = 20, p = 0), and for femoral catheters (R1 = 9 +/- 6.56%, R2 = 29.2
      +/- 11.8%, n = 20, p = 0). Statistically significant differences were also found
      between R1 of jugular catheters and R1 of subclavian catheters (2.38 +/- 1.09%, n
      = 16 and 3.03 +/- 3.15%, n = 20, p = 0.0001), further on between R1 of jugular
      and R1 of femoral catheters (2.38 +/- 1.09%, n = 16 and 9 +/- 6.56%, n = 20, p =
      0), as well as between R1 of subclavian and R1 of femoral catheters (2.38 +/-
      1.09%, n = 20 and 9 +/- 6.56%, n = 20, p = 0.0001). Also statistically
      significant differences were found between R2 of jugular and subclavian catheters
      (7.59 +/- 1.42%, n = 16 and 15.8 +/- 7.18%, n = 20, p = 0.0003), between R2 of
      jugular and femoral catheters (7.59 +/- 1.42%, n = 16 and 29.2 +/- 11.8%, n = 20,
      p = 0.0007), and between R2 of subclavian and R2 of femoral catheters (15.8 +/-
      7.18%, n = 20 and 29.2 +/- 11.8%, n = 20, p = 0.0029). The measurements of urea
      reduction ratio that we have done for some of the catheters under R2 conditions
      showed a statistically significant difference between femoral and subclavian
      catheters (51.45 +/- 5.62%, n = 20 and 63.75 +/- 7.61, n = 20, p = 0), and
      between femoral and jugular catheters (51.45 +/- 5.62%, n = 20 and 64.3 +/-
      5.23%, n = 16, p = 0). No statistical differences were found in urea reduction
      ratio between jugular and subclavian catheters (64.3 +/- 5.23, n = 16 and 63.75
      +/- 7.61%, n = 20, p = 0.8). CONCLUSION: When hemodialysis is delivered by a
      correct blood lines connection the measurements have shown a decrease in urea
      recirculation by 5% for jugular and subclavian catheters, and 5%-10% for femoral
      catheters. However, in cases when the venous lumen of the catheter is used as an
      arterial lumen, and vice versa, urea recirculation is below 10% for jugular
      catheters; whereas in femoral catheters the percentage is higher than 20%.
      Despite so high percentage of urea recirculation, that we obtained for such use
      of the catheters, urea reduction ratio in hemodialysis via jugular and subclavian
      catheters is > 60%, whereas via femoral catheters, the percentage is
      significantly lower. Consequently, the efficiency of hemodialysis is reduced, and
      such use of femoral catheters should therefore be avoided.

PMID- 12812018
TI  - [Smoking cessation using the transdermal nicotine system].
AB  - There are a lot of methods for smoking cessation but transdermal nicotine system
      (TNS) is one of the most popular. On a sample of more than 300 smokers we have
      formerly shown that TNS achieves higher abstinence rate than placebo (38%:21%).
      In the present study we have tested the optimal administration of TNS. 160
      smokers were subdivided in 4 groups of 40, receiving either TNS or placebo, for 3
      or 6 weeks. The abstinence rate was evaluated by appropriate questionnaires and
      measuring CO in the exhaled air. After 3 weeks of TNS 60% of the examinees were
      abstaining compared to 50% after 6 weeks; the abstinence rates in the placebo
      groups were 17.5% and 20%, respectively (p < 0.05). Short TNS treatment (3 weeks)
      is at least as effective as a longer one (6 weeks), which is relevant both
      medically and economically.

PMID- 12812019
TI  - [Diaphragmatic eventration].
AB  - Eventration of the diaphragm is an abnormal elevation of an intact diaphragm.
      There are two distinct etiologic types of eventration, congenital and acquired.
      Congenital eventration is characterized by muscular aplasia, and acquired
      eventration is caused by injury to the phrenic nerve. The one-year-old girl had
      recurrent respiratory inflammations and permanent cough since she was two months
      old. Examinations, such as chest radiogram, chest and abdominal ultrasound, liver
      doppler, computed tomography of thorax and abdomen, did not distinguish
      eventration from possible tumorous formation in the right lower lung. The
      eventration of the diaphragm and atelectasis of the right lower lobe was
      confirmed during the surgery. Diaphragmatic plication was done, and atelectactic
      lobe as well as hypoplastic part of the diaphragm were removed. The eventration
      was confirmed pathohystologically.

PMID- 12812020
TI  - [The variola virus as a biological weapon].
AB  - In view of the threat of use of the variola virus as a biological weapon, the
      interest of medical and other public in this causative agent that was eradicated
      in the wild at the end of the 1970s has increased. The paper gives an outline of
      the current knowledge on biological properties of the variola virus, and on the
      epidemiology, pathogenesis, clinical picture and prophylaxis of the disease
      caused by this virus. Descriptions of two sudden smallpox epidemics (Germany in
      1970 and former Yugoslavia in 1972) could illustrate the potential of the
      smallpox virus as a biological weapon in bioterrorism and biological warfare. In
      fact, this virus can spread very readily through aerosol, which may lead to
      explosive epidemics. Not having been immunised, our population aged less than 25
      years totally lacks the immunity. Older individuals are likely to have a low
      residual specific immunity to the agent. The only way to prevent a smallpox
      epidemic is by vaccination and patient isolation. A rapid smallpox diagnostics
      and prompt vaccination of all contacts is of utmost importance in stopping the
      outbreak.

PMID- 12812021
TI  - [Occupational diseases in instrumental musicians].
AB  - Occupational diseases, work-related diseases and occupational stigma in
      professional musicians are discussed. Predominant diseases and symptoms related
      to various organic systems, such as musculoskeletal, neuromuscular, respiratory
      system, skin, mouth and teeth diseases, as well as the effect of noise and
      psychological stress, have been listed. The preventive measures in order to
      promote health of musicians are described in particular.

PMID- 12812022
TI  - [Toxic effects of benzene and toluene].
AB  - The research of benzene and toluene toxic effects has been carried out in the
      Republic of Croatia. The paper presents the results. The research of early
      indicators of benzene hematotoxicity, immunotoxicity and genotoxicity and toluene
      neurotoxicity has been conducted on the level of methods applicable in the
      occupational medicine preventive activities. Methods appropriate for prevention
      and diagnostics of health impairment of workers occupationally exposed to benzene
      and toluene have been recommended.

PMID- 12812023
TI  - [Comment on the article "Evaluation of residency programs in psychiatry"].

PMID- 12812024
TI  - [Analysis of the health care system transition: what the health care users
      think].
AB  - The project "Analysis of transition of health care system in Croatia" was started
      in order to research the effects of health care system changes. The aim was to
      research specific characteristics of transitional period through evaluation of
      health status, quality of life, and quality of health care. Total of 331 general
      practitioners, 2,252 patients and 5,048 inhabitants were included in the
      research. The Croatian version of SF-36 questionnaire was licensed to Andrija
      Stampar School of Public Health in order to assess health-related quality of
      life. Men, younger and better-educated respondents achieved higher scores in SF
      36 quality of life assessment. Quality of life is lower in Croatia than in
      Western European countries. 85.3% of respondents were satisfied with physicians'
      behaviour. Two components of physician's behaviour were obtained-
      competence/expertise and empathy. These results could contribute to better
      understanding of health care reform effects.

PMID- 12812025
TI  - [Evaluation of residency programs in psychiatry].
AB  - The paper investigates the characteristics of psychiatric residency in Croatia.
      During 1998 psychiatric residents were sent an anonymous questionnaire with
      questions related to obligatory training program in psychiatry according to
      regulations, control system, personal satisfaction, quality, supervising system,
      mentor, lectures, scientific work and literature. Data were analyzed by
      percentage analyses and chi square method. The results show some difficulties in
      respecting the obligatory program during the residency, insufficient supervision
      of clinical work, irregular consultation with mentor and unspecified educational
      material. Residents propose better program transparency, possibility to choose
      between the institutions, standardization of the program, precise definition of
      the mentor and supervision. Implementation of more transparent methods in the
      quality control of the training in psychiatry, as well as the importance of
      harmonization of psychiatric training in Croatia within UEMS requirements is
      suggested.

PMID- 12812026
TI  - [Skrljevo disease in Slovenia].

PMID- 12812027
TI  - [The ALLHAT trial has judged: thiazides are the rule!].

PMID- 12812028
TI  - [Prevention of stroke: should high risk patients be treated with angiotensin II
      converting enzyme inhibitors without regard to their blood pressure levels? ].

PMID- 12812029
TI  - [Bronchial reactivity in patients with seasonal allergic rhinitis].

PMID- 12812030
TI  - [Is it necessary to use morphine in acute pulmonary edema?].

PMID- 12812031
TI  - [Role of occupational medicine in evaluation of work capacity and disability ].

PMID- 12812034
TI  - [Les demoiselles d'Avignon and "e = m.c2"].
AB  - Picasso, mentally travelling around the objects, indicated a process of visual
      disconnection of their naturals forms which ended in the recovery of the
      beautiful lines of euclidean geometry. In this paintings and especially in Les
      Demoiselles d'Avignon, the triangles and circles become plastic materials but
      they do not form perfect euclidean tridimensional spaces where objects must keep
      constant sizes and proportions. Thus, Picasso discovered or invented cubism. The
      characteristic void space of the perspectivistic figurative painting, became
      substituted by a solid space where vertical, horizontal dimensions and depth were
      represented in an instant. This "simultaneity" implicitly included the use of
      time as a fourth dimension in cubist paintings. As in Einstein's relativistic
      theories, in cubism the volume of the observed objects become compressed and
      bidimensional, and the notion of absolute space-time is ignored. In a way,
      cubistic paintings were contemporary illustration of Einstein's relativistic
      principles.

PMID- 12812035
TI  - [The fragility of the self].
AB  - This presentation raises the hypothesis that the "self" is a construction of the
      brain and extremely fragile. In order to support this statement, Prof. Rubia
      provides three different reasonings: firstly, we are not borne with the "self",
      but rather it is the result of development during childhood; secondly, the self
      is subject to cultural influences, so that the perception of this "self" or of
      the own personality varies according to different cultures. And thirdly, the self
      is not indivisible, as shown by epileptic patients with a "split-brain"
      operation, or the psychiatric cases of double personality or the multiple
      personality disorder.

PMID- 12812036
TI  - [Biological potentiality of melatonin].
AB  - The pineal gland is an epithalamic structure whose mission is to integrate
      incoming environmental information with other types of information deriving from
      the inner milieu itself of the organism, releasing melatonin, a substance able to
      elicit responses in the central nervous and endocrine systems. Secreted
      rhythmically during the scotophase, melatonin is involved in reproductive
      mechanisms, in cyclically developing nosological. Processes, and in the genesis
      or maintenance of cerebral biorhythms. Owing to its ability to uptake free
      radicals produced by cell metabolism, it is a potent antioxidant agent that is
      able to delay cellular ageing and inhibit cellular proliferation in both
      experimental and spontaneous tumours.

PMID- 12812037
TI  - [Barrett esophagus and surgery].
AB  - The Barrett esophagus is the substitution of the esophagus distal epithelium
      (scaly) by another one of columnar type (intestinal metaplasia). It is due to the
      gastroesophageal or duodenogastric reflux and other genetic and gotten factors.
      In the diagnosis it is essential to discover the existence and grade of dysplasia
      which constitute the pre-malignant stage of the adenocarcinoma by which vigilance
      is very important. The treatment is the same as the one of gastroesophageal
      reflux and there is no agreement about the advantages of the medical and the
      surgical treatment. The medication (IBP) is effective against the acid reflux but
      doesn't control the duodenogastric in contrast to the surgery (antireflux
      techniques) which is also cheaper and in recent studies it seems to control the
      dysplasia progress.

PMID- 12812038
TI  - [Psychopathology of disasters].
AB  - Psychiatric reactions to disasters have not received sufficient attention because
      it is widely accepted that human beings can endure any kind of extreme stress. A
      disaster is the consequence of an extraordinary event that destroys goods, kills
      people, produces physical or psychological harm but, above all, which overcomes
      the coping possibilities of the social group. Reactions to stress occur in
      stages, each one characterised by a specific psychological mechanisms: pre
      impact, alarm, impact, recoil, post-impact and reconciliation. The reactions can
      be acute or chronic, among them the post-traumatic stress disorder. Symptoms
      include flashbacks, difficulties in remembering, avoidance of stimuli, blunting
      of responses, high arousal level and obsessive ruminations. Biological,
      psychological and social factors play a role in the pathogenesis of these
      disorders.

PMID- 12812039
TI  - [Adult neurogenesis and stem cells. Functional capacity].
AB  - The ability of stem cells to give rise to new neurons in the adult central
      nervous system is a phenomenon that has raised many hopes. The possible doors
      opened by the potentiality of these cells in benefit of neurological patients are
      numerous. But we need more research and facts to avoid raising false
      expectations. There is no sound scientific proof to sustain the excitement
      created by embryonic stem cell therapy. In general, because this therapy is still
      a distant goal; in particular because the widespread degenerative processes
      underlying Parkinson's and Alzheimer's diseases make complete repair through
      transplant practically impossible. It is also hard to understand why research in
      human embryonic stem cells is being promoted when there are no previous sound
      results using animal embryonic stem cells. In addition, there are existing
      alternatives to embryonic stem cells, without ethical problems, that can obtain
      cells to restore damaged adult tissues, using more promising techniques with
      already contrasted results.

PMID- 12812040
TI  - [Brain and consciousness].
AB  - The philosophical and biological concepts of consciousness are briefly reviewed,
      from Aristoteles to Descartes to the modern neurobiologist of the last 15 years.
      The CRICK's corticothalamic integration view, the Edelman's primary and higher
      order consciousness concept as well as the Edelman and Tononi's dynamic core
      concept were discussed. Then the corticothalamic resonance theory by Llinas was
      reported. Central to Llinas's theory is the existence of electrical intrinsic
      properties of neurones in the central nervous system that allows them to
      oscillate at different frequencies and if the membrane properties are suitable
      also to resonate at specific frequencies. From this oscillation and the neuronal
      connectivity result the corticothalamic dynamic loops specific and non specific.
      The dynamic corticothalamic loop of the specific thalamic nuclei connect directly
      as well as through the inhibitory interneurones in layer 4, with the pyramids in
      layer 5 and 6. The pyramids's rhythmic discharge excite the thalamic specific
      neurones and indirectly through the reticular neurones a rebound burst is also
      generated in the specific relay neurones. The oscillatory properties of cortical
      inhibitory interneurones initiates the action of the recurrent circuit whose
      function is to inform the cerebral cortex of the content of the sensory pathways.
      On the other side, the thalamocortical resonant loops of the non especific
      nuclei, particularly the intralaminar, connect with theapical dendrites of layer
      1 pyramids whose discharge go to the thalamic relay neurones directly and through
      the reticular nucleus. The clinical and MEG data are consistent with the
      suggestion that the intralaminar nucleus works as providing the binding signal to
      the sensory specif le information conveyed by the specific pathways. In this way
      the non specific corticothalamic loop would act as the conjunction mechanism
      along the dendritic apical shaft with the specific sensory information. The
      specific loop will give the content and the non specific loop the context.
      Conciousness would be the final result of the summation of specific and non
      specific 40 Hz activity conveyed by the resonant corticothalamic loops.

PMID- 12812041
TI  - [Development of a porcine experimental model of alcoholic intoxication].
AB  - Despite important epidemiologic suggestions that alcohol causes a variety of
      cardiovascular abnormalities, and particularly cardiac arrhythmias, the
      demonstration of this causal effect in animal models is still lacking. Previous
      open-chest models, heavily instrumented and using epicardial stimulation have
      failed to demonstrate such causal effect. We developed a porcine, closed-chest
      model with sedation, a rigorous control of venous alcohol concentration and
      endocardial electrical stimulation, in a multidisciplinary framework. In this
      model, we observed that the infusion of alcohol facilitated atrial
      tachyarrhythmias. This model is available to study a variety of alcohol effects
      "in vivo", in a controlled fashion.

PMID- 12812042
TI  - [Reactions of derivatives of beta-lactam antibiotics with non-antibacterial
      biological activity].
AB  - Beyond the well-known antibacterial and beta-lactamase enzyme inhibiting
      properties of the different beta-lactam antibiotics and their modified
      derivatives there are a number of beta-lactam (azetidine-2-one) compounds
      possessing different biological activities. Most of them have been shown to
      inhibit a variety of cysteine or serine protease enzymes comprising plants,
      viruses, protozoa, bacteria and mammalian species. This review article covers the
      biologically active beta-lactam compounds but beta-lactam antibiotics or beta
      lactamase inhibitors, and including a few chemically related gamma- or delta
      lactams or azetidines presumably having the same site and mechanism of action.
      These include viral protease inhibitors, protozoan enzymes (e.g. cruzain,
      falcipain), plant enzymes (papain). Of the mammal enzymes the most important ones
      are cholesterol absorption inhibitors and human leucocyte (neutrophyle) elastase
      inhibitors, but mention must be made on thrombin, chymotrypsin, cathepsin,
      prostata specific antigen and tumor necrosis factor inhibitors, as potential
      future remedies of cardio vascular and inflammatory diseases.

PMID- 12812043
TI  - [Doping agents and their analytical control].
AB  - Doping is defined as the use of substances and/or forbidden methods for the
      artificial performance-enforcement of an athlete during competition or in the
      preparation period. A survey is given on the misuse of doping agents in recent
      years, with special emphasis on stimulants, beta blockers, diuretics, exogenous
      and endogenous steroids and peptide hormones. The introduction of new doping
      substances including perfluorocarbons, ecdysteroids, synthetic hemoglobin and
      peptide hormones (e.g. growth-hormone) precursors is described. Hyphenated
      separation techniques achieved great progress in doping analysis and control, of
      which some of the recent methods such as LC-MS, GC-MS CE-MS are briefly reviewed
      here.

PMID- 12812044
TI  - [Analysis of antibiotic consumption of five different clinical departments,
      especially considering the features of hematology departments].
AB  - The importance of antibiotic consumption and bacterial resistance analysis is
      unquestionable. Although the WHO has been recommending the use of ATC/DDD method
      for the analysis of drug utilization for about 20 years, only limited numbers of
      publications are available considering the antibiotic consumption of in-patients.
      In the present study--with the help of the mentioned method--we analysed the
      utilization of antibiotics in 5 clinical departments. We also investigated the
      connection between antibiotic consumption, bacterial resistance and enterococcal
      sepsis at the haematologic department. We could follow the successful impact of
      the implementation of the new guideline.

PMID- 12812045
TI  - [Importance of drug utilization studies as a pharmaceutical tool for the practice
      of evidence-based medicine].
AB  - Application of the theory of the Evidence-based Medicine into the every day
      practice means critically appraising the evidence for validity and clinical
      usefulness. The real therapeutic value & place of different drugs could be
      determined only according to the internationally standardised drug statistics.
      The method for drug consumption analysis recommended by WHO is the ATC/DDD
      methodology. The basic features of this method will be summarised by the author
      as well as the usefulness of the data given by utilization researches especially
      regarding the validation of evidence-based practice and the basis of decision
      making processes.

PMID- 12812046
TI  - [A novel decarboxylation method for the preparation of 5,6,7,8,10-hexahydro-5.9
      methanobicyclobenzocyclooctene].
AB  - Several methods were described earlier for the synthesis of 5,6,7,8,9,10
      hexahydro-5,9-methanobicyclobenzocyclooctene (5). A novel simple method is
      described in this paper by the persulfate (II)/silver (I) ion catalyzed
      decarboxylation refluxing in water-acetonitrile mixture from corresponding 4
      carboxylic acid, which was prepared earlier in four steps starting from
      tetrahydrophthalic anhydride (1).

PMID- 12812047
TI  - [Peripheral nociceptin levels in Wilson disease].
AB  - Plasma level of nociceptin, the endogenous agonists of orphaninFQ/OP4 receptor
      was found to be significantly elevated in Wilson's disease patients (14.87 +/-
      2.44 pg/ml +/- SD, p < 0.001, n = 21) compared to age-matched healthy controls
      (9.18 +/- 1.63 pg/ml +/- SD, n = 25). Wilson's disease is an autosomal recessive
      disorder caused by mutation of the gene ATP7B leading to toxic copper
      accumulation mainly in the liver and brain and in other organs such as, kidney
      and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex
      differences nor correlation between plasma nociceptin levels and liver function
      test results were found in Wilson's disease patients. It is suggested that
      significantly elevated plasma nociceptin level is due to the inhibition of
      nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N, endopeptidase
      24.15) by the toxic copper levels, as it is known that changing the central Zn
      atom to Cu results in an approximately 50% inhibition in the activity of these
      enzymes. The high plasma nociceptin level in Wilson's disease patients may induce
      significant impairment in nociceptinerg neurotransmission.

PMID- 12812048
TI  - [The protective effect of EGb 761 in isolated isochemical/reperfused rat hearts].
AB  - This study was conducted to evaluate the effect of Ginkgo biloba extract (EGb
      761) on the nitric oxide (NO) production in relation to the recovery of
      postischemic cardiac function in isolated working rat hearts. Rats were orally
      treated with various doses (25, 50, 75, and 100 mg/kg/day) of EGb 761 for 10
      days. Hearts were isolated in "working mode" and subjected to 30 min ischemia
      followed by 120 min reperfusion. In the initial phase of reperfusion, NO
      production measured by electron spin resonance spectroscopy (ESR) was reduced by
      85% in the 75 mg/kg/day of EGb 761 treated group in comparison with the drug-free
      ischemic/reperfused hearts. Inducible NO synthase (iNOS) messenger RNA (mRNA)
      measured by reverse transcription-polymerase chain reaction (RT-PCR) also was
      reduced by 41 and 58% in the groups treated with 75 and 100 mg/kg/day of EGb 761.
      Our findings show that EGb 761 directly acts as an NO scavenger and concomitantly
      inhibits the expression of iNOS mRNA. Thus, EGb 761 may act as a potent inhibitor
      of NO production under the condition of ischemia/reperfusion, improving the
      recovery of postischemic cardiac function.

PMID- 12812049
TI  - A chimeric mouse model established by allogenic in utero transplantation.
AB  - In utero stem cells transplantation is a promising approach to the prenatal
      treatment of diseases. In order to investigate the fate of the stem cells after
      in utero transplantation, we have established a chimeric mouse model with the
      method of in utero transplantation. Mononuclear cells (including stem
      cells/progenitor cells) derived from male mouse bone marrow were injected into
      fetal mouse peritoneal cavity during the pre-immune period. The donor cells in
      the circulatory blood of female recipients were identified by fluorescence in
      situ hybridization (FISH), and the Y-chromosome specific DNA was detected by PCR
      as well as real-time quantitative PCR after the recipient mice were born. The
      results showed that a total of 4 female recipient mice were chimeric in their
      peripheral blood. Significantly, the donor cells in three chimeric mice persisted
      up to six months.

PMID- 12812050
TI  - [RNA interference directed by small hairpin RNA expressed in COS-7 cells].
AB  - RNA interference is a phenomenon of gene silencing directed by double-stranded
      RNA. It can specifically inhibit gene expression by degrading mRNA efficiently
      and has been widely used to knockdown gene expression in Caenorhabditis elegans,
      Drosophila melanogaster, etc. For mammalian cells, dsRNA directed RNAi was
      detected only in murine undifferentiated ES or embryonic carcinoma (EC) cells.
      Our previous work proved the existence of RNAi effect for reporter gene GFP and
      endogenous gene Oct4 in undifferentiated murine ES cells. Yet in other kinds of
      mammalian cells, because of the existence of interferon pathway, long dsRNA will
      induce the cells to shutdown global protein translation and go to apoptosis.
      Therefore, dsRNA longer than 30 bp cannot be used to induce specific gene
      knockdown effect in these cells. Elbashir et al found that in vitro synthesized
      small interfering RNA (siRNA) (19-23 nt) could induce potent RNAi as effective as
      long dsRNA without showing unspecific effect, so that the interferon pathway
      could be bypassed. It was shown that during RNAi process, long dsRNA was first
      degraded into 19-23 nt siRNA and then recruited into RISC (RNA induced silencing
      complex) to degrade corresponding mRNA. However, the synthesis of siRNA is
      expensive and the effect is transient because the knockdown effect can only be
      maintained for about a week. Recently, it has been shown that U6 promoter
      directed small hairpin RNA (shRNA) can induce potent gene knockdown effect in
      murine P19 Embryonic Carcinoma cell. The RNAi effect of U6 promoter-driven shRNA
      corresponding to Green Fluorescence Protein (GFP) in COS-7 cells was checked. And
      it was found that the U6 promoter-driven shRNA for GFP can specifically and
      potently knockdown the GFP's expression in COS-7 cells. The result established
      the feasibility of using RNAi technique directed by U6 promoter-driven shRNA to
      study genes' function in COS-7 cell line.

PMID- 12812051
TI  - [Expression of grass carp growth hormone in the yeast Pichia pastoris].
AB  - Growth hormone plays an essential role in the stimulation of somatic growth and
      development. To produce large amount of grass carp growth hormone (gcGH) of
      biological activity for further use, this study aimed at high-yield expression of
      gcGH in the yeast Pichia pastoris. The gcGH cDNA was inserted into a yeast
      vector, pGAPZ-alpha-B. Under the control of the promoter GAP (glyceraldehyde 3
      phosphate dehydrogenase), a 22-kilodalton protein, similar to the molecular
      weight of native growth hormone, was detected in the supernatant of transformed
      yeast. It led to a level as high as of 50 mg/L. This protein could be
      specifically immunoprecipitated with rabbit polyclonal antibodies raised against
      gcGH. A receptor ELISA Sandwich method was also performed to verify the
      biological activity of the in vitro expressed gcGH.

PMID- 12812052
TI  - [PCR-SSCP analysis on growth differentiation factor 9 gene in sheep].
AB  - Growth differentiation factor 9 (GDF9) is a growth factor secreted by oocytes in
      growing ovarian follicles, which is essential for growth and differentiation of
      early ovarian follicles. The polymorphism of GDF9 gene in Small Tail Han sheep,
      Hu sheep, Dorset sheep and Suffolk sheep was analyzed by PCR-SSCP. The results
      indicated that there were three genotypes (AA, AB and BB) detected by primer 1.
      AA genotype was detected in four sheep breeds. AB genotype was detected in Hu
      sheep, Dorset sheep and Suffolk sheep. BB genotype was only detected in Suffolk
      sheep. Frequency of A allele was obviously higher than frequency of B allele in
      four sheep breeds. There were two genotypes (AA and AB) detected by primer 2. AA
      genotype was detected in four sheep breeds. AB genotype was detected in Hu sheep,
      Dorset sheep and Suffolk sheep. BB genotype was not detected in four sheep
      breeds. Frequency of AA genotype was the highest, and frequency of A allele was
      obviously higher than frequency of B allele in four sheep breeds. The polymorphic
      fragments amplified by primer 1 were cloned and sequenced. The sequencing results
      showed that there was one single nucleotide mutation: A-->G at cDNA 152 of GDF9
      gene in sheep, and this mutation resulted in an amino acid change: asparagine-
      >aspartic acid.

PMID- 12812053
TI  - [Cloning, genomic organization and promoter activity of the mouse zinc finger
      protein gene ZF-12].
AB  - The human zinc finger protein ZNF191 is a kruppel-like transcription factor,
      which may be relevant to many diseases such as neuropsychiatric, cardiovascular
      and liver caner diseases. To elucidate the function of ZNF191 by gene targeting,
      it is necessary to clone and characterize of the homologous gene in model
      organisms (mice). The mouse homologous gene (ZF-12) was cloned and sequenced for
      the first time, the GenBank accession number is AY052495. It contains four exons
      and three introns; all intronic splice sites exhibited consensus GT/AG sequences.
      The single nucleotide polymorphisms (SNPs) in exon 2 and the alternative length
      of 3'-untranslated region (3'-UTR) have been found. The linkage of the ZF-12 gene
      and the zinc finger protein gene Zfp-35 has been found, so the ZF-12 gene can be
      localized to B3 to C or beside of chromosome 18. We assessed approximately 1.2 kb
      of 5'-flanking region of the ZF-12 gene for basal promoter activity. A series of
      deletion mutants of 5'-flanking region linked to the luciferase gene was
      constructed. Basal level expression of these constructs was tested in COS-7
      cells, NIH3T3 cells and HeLa cells. By measuring luciferase activity, which was
      transiently expressed in the transfected cells, we found that regulatory elements
      sufficient for basal expression lie between -762 and +70 bp relative to the
      transcription start site and that a negative regulatory region lie between -824
      and -762 bp. This research provides a basis for further study on ZF-12 by gene
      targeting.

PMID- 12812054
TI  - [In silicon cloning of the human TECTB gene].
AB  - The coding sequence of the mouse Tectb and chick Tectb gene were subjected to
      Blastn searching against the human dbEST and Htgs in NCBI. One BAC clone
      sequence(GenBank: AL157786) was obtained, which shows high homology to the two
      genes. We predicted the exons and introns in the homologous region of AL157786
      using GENSCAN, MZEF and Blast 2 sequence program, and then assembled the
      predicted exons into the coding sequence of the human TECTB. The open reading
      frame of human TECTB gene is 990 bp composed of ten exons, which encodes a
      protein of 329 amino acids. Human TECTB gene shows 88.1% identity in 990 bp
      overlap with that of the mouse Tectb gene and the predicted polypeptide shows
      94.2% identity in 329 as with the mouse beta-tectorin. The TECTB gene was mapped
      to human chromosome 10q25 by electronic-PCR.

PMID- 12812055
TI  - [Study on the genetic alterations in MTX-resistant cells by differential
      polymerase chain reaction].
AB  - Gene amplification is a common mechanism that contributes to the drug resistance.
      To explore the molecular genetic background related to the MTX resistance in the
      mouse MTX-resistant cells, differential PCR was used to determine the
      amplification and overexpression of DHFR gene. In addition, the correlations
      between c-myc, p53 status and dhfr amplification were studied. Amplification and
      overexpression of dhfr suggested its role in MTX-resistant cells. However, no
      amplification and overexpression of c-myc were detected. On the other hand, no
      alteration of p53 copy number was found. The increased mRNA level of p53
      suggested the normal function of p53. These results implicated the status of c
      myc and p53 had no correlation with dhfr amplification, therefore some other
      molecular genetic alterations may exist to permit the dhfr amplification in MTX
      resistant cells.

PMID- 12812056
TI  - Linkage analysis of the candidate genes of familial restless legs syndrome.
AB  - This research was performed to investigate the relationship between 16 candidate
      genes responsible for dopaminergic transmission or iron metabolism and familial
      restless legs syndrome. Genotyping was performed in a Han restless legs syndrome
      family using the technique of fluorescence-based genescan with the microsatellite
      markers selected in chromosomal regions flanking the candidate genes. Classical
      linkage analysis was conducted under the autosomal dominant genetic mode. Results
      showed that all of the LOD scores at recombination fraction 0.00 are smaller than
      -2.00, which indicated that these loci were not linked to familial restless legs
      syndrome. No linkage was found between the candidate genes and RLS in this
      family. Familial restless legs syndrome may be caused by another gene related to
      dopaminergic transmission and iron metabolism or there is new mechanism involved
      in this disease.

PMID- 12812057
TI  - [A study on introduction of chitinase gene and beta-1,3-glucanase gene into
      restorer line of dian-type hybrid rice (Oryza sativa L.) and enhanced resistance
      to blast (Magnaporthe grisea)].
AB  - Plasmid pBLGC containing chitinase gene from Phaseolus limensis and beta-1,3
      glucanase gene from Nicotiana tabacum was bombarded into the restorer line
      "Nan29" of Dian-type hybrid rice (Oryza sativa L. ssp. japonica) from Yunnan
      province of South-west China. 93 regenerants were obtained from the calli that
      were resistant to G418 (100 to 150 mg/L) on NB medium. Using beta-1,3 glucanase
      gene as the probe, 17 of the regenerants were identified to be transgenic lines
      by dot blotting and the foreign genes construction were integrated into the
      genomes of T1 lines by Southern blotting hybridization. Two foreign genes were
      inherited stably to T4 generation according to PCR results of the lines. The
      resistance to rice blast of six transgenic lines were evaluated by inoculating
      four violent biological races of Magnaporthe grisea from Yunnan province and
      inducing the disease in the field. The results indicated that the resistance to
      rice blast of transgenic lines were enhanced to varying degrees compared with the
      receptor line and the transgenic lines could be used in rice blast resistant
      breeding.

PMID- 12812058
TI  - [Synonymous codon usage bias in the rice cultivar 93-11 (Oryza sativa L. ssp.
      indica)].
AB  - By using the whole genome sequences and EST data from the indica rice cultivar 93
      11, a detailed relative analysis is made of the effect of some impact factors on
      synonymous codon usage. The results showed that the gene expression level
      assessed by mRNA abundance is positive relative to the "codon adaptation index"
      (CAI, 0.227**), and "codon preference parameter" (CPP, 0.145**), but negative
      relative to "effective number of codons" (ENC, -0.147**), indicating that genes
      with higher expression showed more significant variation in codon usage. There
      are significant negative correlations between gene length and CAI, CPP (r = 
      0.413** and -0.480** respectively), but a positive correlation between gene
      length and ENC(r = 0.210**), which suggested a tendency of shorter genes to
      higher expression of the transcriptional activity in 93-11. From the results that
      a higher negative correlation between GC content and ENC(r = -0.740**), but
      higher positive correlations between GC content and CAI, CPP (r = 0.877** and
      0.832**, respectively), we can concluded that the GC content in coding region
      gave far more contribution to codon usage bias than that mRNA abundance and gene
      length. Four kinds of bases showed a three-period distribution in the translation
      initiation region, the bias at the first codon sites, which located +4, and +6,
      in the downstream of ATG being the largest. That suggested that there was a
      strong action of natural selection on these specific positions in the 93-11
      genome. In this paper twenty-five codons defined firstly as "optimal codons" in
      93-11 may provide some more useful information for rice gene-transformation.

PMID- 12812059
TI  - [Genetic mapping of resistant gene to southern corn rust and the tagging analysis
      on different genetic background].
AB  - Southern corn rust (SCR) is a destructive disease in maize. The inbred line Qi319
      is highly resistant to southern corn rust. SSR technique was employed to
      preliminary mapping of the resistance gene. Bulked segregant analysis revealed
      that two primers, phi 118 and phi 041, amplified polymorphic bands. SSR analysis
      on populations indicated the two primers were linked to the rust resistance gene,
      which was mapped on the short arm of chromosome 10. In addition, comparative
      analysis of the amplification bands among different populations revealed that the
      amplification products with the same primer in different populations were
      dissimilar. This result indicates that the genetic background may affect results
      of gene mapping and tagging. So, it is important to select suitable population to
      performing molecular marker analysis and gene mapping.

PMID- 12812060
TI  - [Inducing chromosome translocation and deletions by Chinese Spring-Agilops 2C
      disomic addition x Chinese Spring-Elytriga 5E disomic addition].
AB  - Crossing between two disomic addition lines, Chinese Spring-E. elongata and
      Chinese Sping with two gametocidal chromosomes 2C (from Ae. cylindric), was
      carried out to investigate the function of gametocidal chromosome. After
      scrutinizing the meiosis of pollen mother cells (PMCs) in F1 hybrids, several
      results were concluded: (1) In seven of the crossing combinations, the number of
      univalents exceeded the expected and some trivalents and tetravalents appeared
      also in MI; lagging, breakage and bridge of chromosomes were observed in anaphase
      and telophase; considerable micronuclei formed in telophase and tetrads. These
      were mainly caused by the gametocidal chromosome 2C. (2) Chromosomes 6E and 7E
      were more susceptible to the effect of the gametocidal chromosome 2C. (3) The
      gametocidal chromosome 2C functioned in prophase viz. the period of forming
      synaptonemal complex. Four F1 lines, 5-14, 5-37, 5-67 and 5-71, were identified
      to be T5ES 4AST5EL 2BS, T5EL 3AS, T5ES 5BS translocation respectively by using C
      banding and genome in situ hybrydization(GISH) analysis. Deletion was detected in
      line 5-17 (short arm of chromosome 2A), 5-27(6B), 5-18(4B and 5B), 5-72(4A) and 5
      4(4B) by C-banding analysis. The statistic data showed that gametocidal
      chromosome could induce translocation with a high frequency of 5% and reacted on
      group B more efficiently than on groups A and D since translocation involving
      chromosome 4A, 2B, 3A, 5B and deletion involving chromosome 6B, 5B, 4B, 4A 2A
      according to Endo's work.

PMID- 12812061
TI  - [Development and application of a genome specific PCR marker for Haynaldia
      villosa].
AB  - Random amplified polymorphic DNA (RAPD) analysis was performed on common wheat
      Chinese Spring, H. villosa, addition lines of H. villosa chromosome in CS,
      substitution line 3V of H. villosa chromosome in Triticum aestivum. A genome
      specific polymorphic DNA segment from H. villosa, OPF02757, was obtained. On the
      basis of cloning and sequencing of OPF02757, two PCR primers were designed and a
      genome specific PCR marker for H. villosa was established. The PCR marker
      including 677 bp was localized on all the seven pairs of H. villosa chromosomes.
      The result of PCR amplification by the primers indicated that there was a
      specific band of 677 bp in the materials containing H. villosa Chromosome such as
      T. aestivum-H. villosa addition, T. aestivum-H. villosa substitution, T. aestivum
      H. villosa amphidiploid, T. durum-H. villosa amphidiploid and H. villosum from
      different accessions, and there was no specific band of 677 bp if the materials
      did not contain H. villosa chromosome, such as T. aestivum, T. durum, Secale
      cereale, Hordeum vulgare, Thinopyrum elongatum, Thinopyrum intermedium.
      Therefore, the PCR maker of 677 bp is specific to H. villosa genome, and could be
      used as molecular marker for detection of chromosomes of H. villosa in wheat.

PMID- 12812062
TI  - [Analysis of RAPD markers about sterility gene in cytoplasm-nucleolus interacting
      type rice mitochondrial DNA].
AB  - Two specific fragments OPJ18-1000 and OPJ18-1400 were obtained from mitochondrial
      DNAs of two rice varieties, II-32 and II you 949, by RAPD analysis. The sequenced
      lengths of the two differential fragments were 1068 bp and 1481 bp, respectively.
      The result of Southern hybridization demonstrated that the differential fragments
      were true. When hybridizing with II-32A, II-32B and II you 949 by OPJ18-1000
      probe, we found OPJ18-1000 which had effects on rice II-32A and II you 949
      cytoplasmic male sterility in transcription had not the same effects on II-32B.
      Though RNA dot hybridization was negative, OPJ18-1400 had a conservative domain
      of seven base pairs DNA sequence: 5'-TTCCCTC-3', which was homologous
      recombination hotspot domain in atp6 gene. It was reported that 5'-TTCCCTC-3'
      induced the formation of chimeric gene in mitochondrial DNA and further caused
      rice male sterility. As a result, the two fragments are new mitochondrial DNA
      fragments relevant to rice cytoplasm male sterility by homologous analysis and
      DNA, RNA hybridization.

PMID- 12812063
TI  - [Cloning and sequencing of chitinase gene from Bacillus thuringiensis subsp
      israelensis].
AB  - Chitin, a linear homopolymer of N-acetyl-D-glucosamine, is a common constituent
      of fungal cell walls, exoskeletons of insects, and shells of invertebrates. Thus,
      chitinase, a chitin hydrolytic enzyme, has become of interest for potential use
      as biopesticides for controlling insect pests. Using a pair of specific primers,
      chitinase gene (ichi) was amplified by touchdown PCR from Bacillus thuringiensis
      subsp israelensis chromosomal DNA, and then subcloned into pGEM-T easy vector.
      ichi sequence (GenBank Accession Number: AF526379) with a length of 2570 bp
      included an open reading frame (ORF) of 2067 bp, which contained 688 amino acids
      with Mr = 75.79 kDa and pI = 5.90. The amino acid sequence of ichi gene shows
      97.24%, 97.18%, 97.63% and 63.07% identity to that of Bacillus cereus strain 28-9
      chitinase CW, Bacillus cereus CH chitinase B, Bt subsp Mexican chitinase, and Bt
      subsp pakistani chitinase A71, respectively. It was demonstrated that Ichi
      contains a signal peptide (46 amino acid residues) and three functional domains:
      an N-terminal catalytic domain (105 amino acid residues), a fibronectin type III
      like domain (74 amino acid residues), and a C-terminal chitin-binding domain (40
      amino acid residues).

PMID- 12812064
TI  - [Effect of growth, temperature and media on the expression of secE promoter of
      Streptomyces lividans TK24].
AB  - Streptomyces are Gram-positive, filamentous soil bacteria, which produce a wide
      variety of metabolites that are currently being exploited in both medicine and
      agriculture. Moreover, Streptomyces lividans is used as a host strain to
      effectively express and secrete heterologous proteins to culture media. Genes
      encoding Sec proteins responsible for the translocation of preproteins have been
      identified in S. lividans. SecYEG, a complex of integral membrane proteins SecY,
      SecE, and SecG in the cytoplasmic membrane, constitutes a pathway for polypeptide
      movement. SecA plays a central role in translocation as it is the site of
      preprotein entry into the translocase and it is the only ATPase essential for
      preprotein translocation. The role of SecD and SecF is to regulate the movement
      of the translocating protein. A better understanding of their regulatory
      mechanism could help to develop S. lividans strains with hyper-secretory
      capacity. In this study, a reporter system was used to investigate the regulatory
      mechanism of secE promoter. Upstream sequence (496 bp) of secE of S. lividans
      TK24 was cloned and characterized in a promoter probe vector pIJ4083 upstream of
      promoterless xylE. Sequencing analysis revealed that secE upstream sequence of S.
      lividans shares 99.8% homology with the secE promoter of S. coelicolor. The
      transcriptive activity of this fragment approximates vsi promoter in CMI medium,
      a strong promoter from S. venezuelae. The activity of secE promoter was observed
      in different growth phase, culture temperature and culture media. The expression
      level of secE was higher during the log phase, but decreased at the beginning of
      the stationary phase. At growth temperature of 28 degrees C, the expression level
      was much higher than that at 37 degrees C. When the bacteria were incubated in
      NB, Phage, and CM medium respectively, the expression level of secE promoter was
      different at a certain fermentation time, but all reached the highest level at
      log phase. Further analysis revealed that glucose may repress secE promoter
      expression.

PMID- 12812065
TI  - [rpsL gene analysis associated with Streptomycin resistance in Mycobacterium
      tuberculosis].
AB  - The mutation of the rpsL gene in Mycobacterium tuberculosis (M.TB) is related to
      Streptomycin resistance. In this experiment, 77 TB strains obtained in hospital
      were selected, the routine drug susceptibility test was done by using BACIEC460
      system, meanwhile the TB-rspL gene was amplicated by PCR, and analyzed by SSCP,
      RFLP and sequence analysis. There are 20 strains sensitive to SM and 57 strains
      resistant to it in routine drug susceptibility test. The SSCP result displayed
      that 34 strains were rspL gene wild type and 43 strains were mutant type.
      Compared with routine drug susceptibility test, the specificity was 95% and the
      positive anticipate value was 98%. RFLP cut by MobII displayed that 81.4% of
      mutation happened in codon 43 of TB-rspL. Sequence analysis displayed that there
      was single base mutation in codon 43(AAG-->AGG). In conclusion, Drug resistance
      of TB to SM is related to rspL gene mutation and the mutation in codon 43 is the
      most common cause.

PMID- 12812066
TI  - [Development of gene therapy for hematopoietic stem cell using viral vectors].
AB  - Hematopoietic stem cells (HSC) are attractive targets for gene therapy of
      inherited and acquired disorders in hematopoietic system in that they possess the
      properties of self-renewal, proliferation, and multi-lineage differentiation. For
      successful gene therapy, the viral vector-mediated gene addition strategy has two
      essential prerequisites: 1) the efficient transfer of therapeutic gene into HSC;
      2) the long-term and stable expression of the transgene at therapeutic levels.
      The oncoretrovirus-derived vectors are best understood and most widely
      investigated. Recent successful cases of gene therapy for severe combined
      immunodeficiency due to adenosine deaminase or gamma c chain deficiencies have
      provided strong evidences that retrovirus-mediated gene transfer into HSC will
      work in clinical treatment. While these results are encouraging, some obstacles
      remain to be circumvented including low efficiency of gene transfer and gene
      silencing in retroviral vector system. The therapeutic gene can be efficiently
      introduced into HSC by HIV-1-based lentiviral vector due to its capability to
      infect the quiescent cells. A variety of preclinical studies are now conducted
      and a number of valuable results highlight the efficacy of lentiviral-mediated
      gene transfer into HSC. However, the potential value of lentiviral vectors in
      human gene therapy remains to be demonstrated. Adeno-associated virus vector is
      an alternative to retroviral and lentiviral vectors. This review summarizes the
      characteristics of integrating vectors, the improved HSC transduction protocols,
      and the optimized gene expression strategies and outlines the important advances
      of preclinical and clinical trials in hematopoietic stem cell gene therapy.

PMID- 12812067
TI  - [The thirty years of Acta Genetica Sinica].
AB  - Acta Genetica Sinica (AGS) is sponsored by the Genetics Society of China and the
      Institute of Genetics and Developmental Biology of Chinese Academy of Sciences,
      and is published by Science Press. The journal is a leading national academic
      periodical and one of the Chinese key periodicals of natural sciences. Currently,
      AGS is being indexed by several well-known domestic and international indexing
      systems, such as the American Chemical Digest (CA), BIOSIS database, Biological
      Digest (BA), Medical Index and Russian Digest (P [symbol: see text]). Papers in
      the areas of genetics, developmental biology, cell molecular biology and
      evolution are regularly published by AGS.

PMID- 12812068
TI  - [cDNA cloning, subcellular localization and tissue expression of a new human
      Kruppel-like transcription factor: human basic Kruppel-like factor (hBKLF)].
AB  - The FLD4585 clone from the cDNA library of human fetal liver may encode a
      hematopoietic related transcription factor. Here we tried to clone its full
      length cDNA from the 22 weeks-gestation human fetal liver and study its
      functional domains, genomic structure, chromosomal localization, subcellular site
      and expression pattern. To obtain the full-length cDNA of FLD4585 clone, 5' RACE
      technique was used. Bioinformatics was used to analyze its genomic structure,
      chromosomal localization and potential functional domains. Its subcellular
      localization was shown by GFP fusion technique. The expression pattern was
      studied by Northern blot, RT-PCR and Western blot. The results show the full
      length cDNA encoded by FLD4585 clone is 1810 bp long and encodes a 345 amino
      acids protein with high homology to mouse BKLF (basic Kruppel-like factor). Its
      characteristic C-terminal three contiguous C2H2 zinc fingers place it within the
      family of Kruppel-like factors. Bioinformatics studies show hBKLF gene spans over
      33 kb on chromosome 4p15.2-4p16.1 and contains 6 exons and 5 introns. GFP-hBKLF
      fusion technique showed hBKLF was present in the nuclei of COS-7 cells in a
      punctate pattern, whereas it was absent in the nucleoli. By Northern blot, hBKLF
      has two transcripts, one between 4.4 kb-7.5 kb and the other between 1.35 kb-2.4
      kb. The larger transcript exists widely in human tissues. However, the smaller
      transcript was more restricted in blood leukocytes, liver and bone marrow. RT-PCR
      showed erythrocytes and granulocytes could both express hBKLF and its level
      increased as they matured. The expression level in fetal liver decreased as it
      developed towards adult liver and its hematopoietic function gradually lost.
      Taken together, in this paper we have successfully cloned the full length cDNA of
      hBKLF. Expression study suggests it may have broad functions in vivo, especially
      the functions in hematopoietic tissues.

PMID- 12812069
TI  - Detecting haplotypes of DXS7132 and DXS6804 loci by multiplex PCR.
AB  - DXS7132 and DXS6804 were amplified by means of multiplex PCR and detected by
      polyacrylamide gel electrophoresis and silver stain. Population study has been
      carried out in Guangdong Han Population of South China. DXS7132 exhibited 7
      distinguishable alleles ranging from 276-300 bp in size. Number of alleles at
      DXS6804 was 6 and its range was 177-201 bp. Sequencing revealed that their common
      sequence motifs were tetranucleotide repeats. On the genomic mapping information
      linkage disequilibrium between DXS7132 and DXS6804 was shown. Female haplotypes
      were determined by analyzing family trios. In 827(211 males, 616 females)
      chromosomes, total 33 haplotypes were identified. Deviation from Hardy-Weinberg
      equilibrium was not detected in the female diploid data. Gene diversity,
      polymorphism information content and probability of exclusion for the two loci
      were 0.9999, 0.9440 and 0.9411, respectively. Investigation in 308 family trios
      suggested a co-dominant X-linked inheritance and mutations were not found. The
      result indicates that DXS7132 and DXS7132 will be very useful for paternity
      testing that involve a female child, especially for the deficiency parents cases.

PMID- 12812070
TI  - [Studying the polymorphism at DYF155S1 locus in Chinese Han population by MVR-PCR
      marked with fluorescence].
AB  - The simple and useful genotyping methods of DYF155S1 locus by silver staining and
      fluorescence detection have been established. The blood samples from 155
      unrelated males in Chinese Han population were typed by these two methods
      respectively and the same results were obtained. Among the 155 samples 66 alleles
      were found, out of them 38 were observed once only. The most frequent alleles
      named 18 or 22, which frequency was 0.065, the size of their first DNA fragments
      was 180 bp and the number of fragments was 16 or 17. The gene diversity (h) was
      0.9789. Out of the 155 samples, 25 samples had one or two bands lost (null
      repeat) among the successive bands. It was demonstrated by sequencing that the
      position of the lost bands corresponded to type 3 repeats. Our results indicated
      that the method, which revealed the 5' end diversity of DYF155S1 locus, was a
      technique that could obtain the most Y-specific polymorphic information only by
      one PCR reaction. The allele frequencies of DYF155S1 locus in Chinese Han
      population provided the basic data for the study of population genetics and
      forensic practices.

PMID- 12812071
TI  - [Expression of the human extracellular domain of high density lipoprotein
      receptor in methylotropic yeast].
AB  - HDL receptor plays a very important role in reverse cholesterol transport, and it
      represents a novel therapeutic target for atherosclerosis. For construction of an
      in vitro high-throughput drug screening model based on competitive receptor-
      ligand binding, the extracellular domain of HDL receptor was expressed in the
      methylotropic yeast Pichia pastoris. The DNA fragment encoding for extracellular
      domain of HDL receptor was cloned by RT-PCR from Hepatoma Bel-7402 total RNA and
      the nucleotide sequence of the cloned cDNA was verified by inserting it into pGEM
      T vector. Then the cDNA was subcloned into pPIC9K, the integrative secretory
      expression plasmid of Pichia pastoris was constructed, with the methanol
      inducible alcohol oxidase promoter and alpha-signal peptide. The recombinant
      plasmid was transformed into Pichia pastoris GS115 (His- strain) by
      electroporation. PCR was used to confirm the insertion of HDLR gene into the
      genome of Mut+ transformants. During cultivation the recombinant strain was
      induced by 1% methanol and supernatant was analyzed by SDS-PAGE and Western blot.
      The result showed a specific protein band at approximately 64.5 kDa after 5 days
      of induction. Then the ligand binding activity was confirmed using the DiI-AcLDL
      as ligand.

PMID- 12812072
TI  - [Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1
      and Mtsarg1 and expression analysis for Mtsarg1 gene].
AB  - Spermatogenesis cell apoptosis is a very complex process, which needs many
      molecules to take part in the programmable death of cells in testis. At present,
      research of apoptosis for spermatogenesis cell is at the primary step. It is very
      important to clone spermatogenesis cell apoptosis related genes and
      spermatogenesis genes in testis. Applying the bioinformatics and experiment
      technique, we have cloned human and mouse novel gene cDNA sequences--human testis
      and spermatogenesis cell apoptosis related gene 1 (TSARG1) and mouse testis and
      spermatogenesis cell apoptosis related gene 1(Mtsarg1) from human and mouse
      testis cDNA library respectively, using a cDNA fragment (GenBank accession
      number: BE644538) as an electronic probe, which was significantly changed in
      expression in cryptorchidism. The GeneBank accession numbers of Mtsarg1 and
      TSARG1 are AF399971 and AY032925 (NM_139073), respectively. The Mtsarg1 has a 55%
      identity and 61% similarity with TSARG1 at the amino acid level, which did not
      share significant homology with any other known protein in databases. The full
      length cDNA of TSARG1 gene is 973 bp, including 549 bp open reading frame(ORF)
      and coding 183 amino acids, whereas the full-length cDNA of Mtsarg1 gene is 1103
      bp, including 576 bp ORF and coding 192 amino acids. The predicted molecule
      weight of TSARG1 is 19948.61 Dolton, and the deduced iso-electric point is 10.24,
      whereas the Mtsarg1 is 20875.93 and is 9.83, being alkaline proteins. RT-PCR
      analysis showed that Mtsarg1 was expressed significantly in testis and faintly in
      epididymis in the ten tissues of testis, ovary, spleen, kidney, lung, heart,
      brain, epididymis, liver and skeletal muscle in mouse, while it wasn't expressed
      in the other eight tissues. Therefore, our results suggested that Mtsarg1 and
      TSARG1 would be pay potential roles in spermatogenesis cell apoptosis or
      spermatogenesis.

PMID- 12812073
TI  - [Single nucleotide polymorphism analysis in sow mu opioid receptor gene exon
      III].
AB  - Stereotypies are the most common abnormal behaviours in sows. Stereotypies are
      repeated, relatively invariable sequences of movements which have no obvious
      purpose. Mu opioid receptor is a member of G protein-coupled receptor family,
      distributed in the pain transduction region in the brain and related emotion and
      behavior regions where influence the animal neural reaction and behavior. The
      possibility of the MOR gene as the candidate gene to affect the stereotyped
      behavior traits in sows was discussed in this study. The primer of sow MOR gene
      exon III partial sequence was designed to analyze single nucleotide polymorphisms
      by PCR -SSCP in Landrace, Yorkshire and Duroc breeds. Two polymorphisms were
      found, which was caused by a single nucleotide mutation of C to T and C to A at
      the positions of 1169 and 1226, respectively compared with the sequence in
      GenBank, but it was the silence mutation. The results of chi 2 test showed that
      the frequencies of genotypes resulted in different breeds were significantly
      different (P < 0.01). The least square analysis between the nucleotide acid
      mutant induced three genotypes and the stereotyped behavioral traits in Yorkshire
      showed that individuals with BB genotype have significant higher (P < 0.01) sham
      chewing behavior than those with AA genotype, but not for bar-biting and
      standing. According to the above results, we can putatively draw the conclusion
      that MOR gene is probably the major gene affecting the sham-chewing behavioral
      traits or linked to the major gene.

PMID- 12812074
TI  - Primary factors affecting the evaluation accuracy of animal model MBLUP.
AB  - Marker-assisted best linear unbiased prediction (MBLUP) is one important method
      of implementing marker-assisted selection (MAS). The computer stochastic
      simulation method was used to study the effects of heritability of trait, QTL
      variance and map distance between two adjacent markers on the evaluation accuracy
      of animal model MBLUP. With the higher heritability, the smaller QTL variance and
      the shorter map distance between two adjacent markers, the evaluation accuracy of
      animal model MBLUP would be increased. On the contrary, the evaluation accuracy
      of animal model MBLUP would be decreased when the heritability was lower, QTL
      variance was larger and map distance between two adjacent markers was longer.

PMID- 12812075
TI  - Genetic analysis of the low critical sterility temperature point in photoperiod
      thermo sensitive genic male sterile rice.
AB  - It has been a long haul but photoperiod- and thermo-sensitive genic male sterile
      (PTGMS) rice has not been freely used in hybrid rice production because there are
      two perplexing problems corresponding to the critical sterility temperature point
      (CSTP): the uncertainty of the CSTP segregating pattern and the instability of
      CSTP for every originally useful line. N5088S, the most widely commercialized
      japonica-type PTGMS line in China, also saw that its CSTP variants have been
      isolated but with all other agronomic characteristics unchanged. In this report
      we analyzed the genetic basis of CSTP, by employing the iterated expectation and
      conditional maximization (IECM) algorithm on four tiller-splitting-formed sets of
      seven generations from N5088S and its CSTP-variant H5088S, each set treated with
      one temperature regime. The main results indicated that there are two dominant
      major genes and polygene, as well as their respective epistasis conditioning the
      CSTP in the 23.5 degrees C regime. Based on the results obtained, the strategy
      for breeding of PTGMS lines with stable low CSTP was outlined.

PMID- 12812076
TI  - Cloning, mapping and protein expression of wheat thaumatin protein gene (TaTLP1).
AB  - To understand wheat powdery mildew resistance mechanism, reverse-transcription
      polymerase chain reaction (RT-PCR) and cDNA library screening were performed to
      isolate the full-length cDNA of wheat thaumatin protein gene from wheat-Haynaldia
      villosa 6VS/6AL translocation line. The putative amino acid sequence of this gene
      consists of 173 amino acid residues, and is an acid polypeptide. It was highly
      homologous to thaumatin proteins isolated from other plants, so it is designated
      as TaTLP1 (GenBank accession number: AF384146). Northern blot analysis of TaTLP1
      showed that the transcription difference obviously existed between resistant
      wheat-Haynaldia villosa 6VS/6AL translocation line and susceptible "Yangmai 5".
      The result of western blot showed that the protein expression product of TaTLP1
      gene in wheat seedling leaf was a soluble cytoplasm protein, whose expression was
      induced by fungus Erysiph graminis and apparently related to disease resistance
      of the 6VS/6AL translocation line. Southern blot indicated that the TaTLP1 gene
      had 1-2 copies in wheat genome, and had been localized on the specific region of
      7B and 7D chromosomes in wheat.

PMID- 12812077
TI  - [Differential expression of genes related to photoperiod-temperature sensitive
      genic male sterility in wheat, revealed by mRNA differential display using G-box
      family primer].
AB  - mRNA differential display with G-box family primer was used to analyze the
      differential expression of genes of the photoperiod-temperature sensitive genic
      male sterile(PTSGMS) line of wheat, BAU3338, between the sterile and fertile
      conditions. The result indicated that gene expression was significantly different
      between the two types of condition during the fertility transformation phase. The
      twelve qualitatively different DNA bands were identified with reverse Northern
      blot hybridization and five positive clones, HT1-G10, HT1-G3, HT2-G2, HT1-G4 and
      HT2-G5 were sequenced. The homology search indicated that HT1-G10 was highly
      homological (96%) to the partial sequences of Triticum aestivum chloroplast
      genes, rbcL and atpB, HT1-G3 was also homological (88%) to Triticum aestivum
      histone H2A gene and the other three gene fragments were new sequences in Gen
      Bank. The analysis of the candidate gene fragments supplied some effective
      evidences to reveal the developmental mechanism of PTSGMS.

PMID- 12812078
TI  - [Cloning and sequencing of ACC oxidase gene from sugarcane].
AB  - The plant hormone ethylene is not only responsible for the initiation of fruit
      ripening, senescence and dormancy but also for regulating many other plant
      developmental processes, such as seed germination, root initiation, growth,
      floral differentiation, sex differentiation and responding to environment
      stresses. One of the rate-limiting steps for ethylene biosynthesizing in plant is
      catalyzed by 1-aminocyclopropane-1-carboxylate (ACC) oxidase. Understanding of
      ethylene expressive pattern in plant is an entrance to understand the roles of
      ethylene on plant. In this paper, two degenerate oligonucleotide primers were
      designed, coding for two conservative amino acid regions in ACC oxidase protein
      family, the sequences of the two primers were TAGAGCTCGATGC[TA]TG
      [CT]GA[GA]AA[AC]TGGGG and CGTCTAGAGCTTC[GA]AATCTTGGCTCCTT respectively. A PCR
      amplification was performed on sugarcane (Saccharum L. Hybrid cv. ROC16) DNA
      template, and produced a fragment of 940 bp. By using the program of BLAST on
      NCBI GenBank database, the sequence presented a very high match with the ACC
      oxidase genes from other plants, 63 searched out sequences were all ACC oxidase
      genes. After alignment on PCgene program, the identities of the cloned fragment
      with ACC oxidase genes from rice and bamboo were both reaching about 88%. So we
      can concluded that the cloned sequence was a member of ACC oxidase genes fragment
      from sugarcane. The sequence has been submitted to the GenBank database, the
      accession number is AF442821. According to the ACC oxidase protein family, a
      'intron' of 103 bp was excluded and the sequence coded 279 amino acids, which
      spanned 88% of the putative whole sequence in length. Alignment and phylogenetic
      analysis of the amino acid sequence deduced from this fragment and the ACC
      oxidase sequences of other plants retrieved from GenBank were carried out by
      using PCgene program. The putative amino acid sequence shared a homology of 86%
      with the ACC oxidases of bamboo and rice, 74.6% with banana, 70% with tomato and
      potato and 68% with melon and carnation, which showed that the homology of
      sugarcane ACC oxidase with monocot was higher than with dicot. The results of
      phylogenetic analysis showed that ACC oxidase from sugarcane and ACC oxidases
      from rice clustered together firstly, and then came those from banana, ACC
      oxidases of dicot from potato, tomato, petunia, melon, Arabidopsis thaliana and
      carnation came subsequently. It indicated that sugarcane ACC oxidase had a closer
      phylogenetic affinities to the monocot ACC oxidase sequences than to the dicot
      ACC oxidases sequences. The clustering results of ACC oxidase molecules accorded
      with morphological classification system.

PMID- 12812079
TI  - [Virus resistance in transgenic watermelon plants containing a WMV-2 coat protein
      gene].
AB  - Virus disease is a major cause that affects the quality and output of watermelon
      which is an important fruit in summer. So it is really urgent to develop disease
      resistance plants. But it takes a long time to breed such plants in conventional
      ways, and it is very difficult to get ideal result. With the development of plant
      genetic engineering, new ways have been found to breed plants with disease
      resistance. By using plant transgenic technique, much progress was been made in
      plant improvement. There are many successful cases of transgenic plants against
      corresponding virus disease through transferring coat protein gene. This paper
      reports the results of inheritance, segregation, expression of WMV-2 coat protein
      gene in inbred transgenic watermelon and its resistance to virus. Through PCR
      analysis of inbred plants, we found WMV-2 coat protein gene in the genome of
      progeny R1 separated with 3:1. After successive selection and identification of 4
      generations, 8 transgenic pure lines with almost the same agronomic traits were
      obtained from 3 independent transformants of T7, T11 and T32. The result of
      Western blotting shows all 3 different transgenic lines of R4T7-1, R4T11-3 and
      R4T32-7 can produce coat protein. Disease resistance experiment on transgenic
      plants with WMV-2 shows that, compared with the control groups, transgenic plants
      can delay the disease infection and reduce the incidence and the symptoms of
      virus disease. And the transgenic line R4T32-7 expressed high resistance to
      infection by WMV-2, which lays a foundation for breeding of disease resistant
      varieties through plant transgenic technique.

PMID- 12812080
TI  - [Genetic analysis of isozyme loci of intraspecific hybrid in Auricularia
      auricula].
AB  - Monokaryon strains H2 and J3 were respectively developed from the cultivated
      strains He-1 and Ju-1 of Auricularia auricula through protoplasted monokaryon
      technique. Dicaryon strain H2J3 was bred through crossbreeding of H2 and J3 as
      parents. Fifty-two F1 monokaryon strains were obtained from the fruitbodies of
      dicaryon H2J3 of A. auricula by the single-spore isolation and culture. All the
      tested strains, parent monokaryon strains (H2,J3) and fifty-two F1 monokaryon
      strains, were cultured in liquid Complete Yeast Medium(CYM) for twenty days, and
      the mycelia of tested strains were respectively analysed by polyacrylamide gel
      electrophoresis. Bian Y B et al. have reported the results of isozyme zymogram
      polymorphisms of cultured strains including He-1 and Ju-1, and the specific
      expression of esterase genes on the different stages of mycelial development in
      A. auricula. The same named methods of isozyme loci and alleles suggested by
      Gottlieb (1973) were used in this study. The relative fitness of allele
      segregation and theoretical expected ratio was examined by the contingency chi 2
      test. The linkage relationship was assessed according to the method suggested by
      Rudin and Ekberg (1978). The isozyme analysis of tested strains showed that the
      isozymes of esterase (EST), malate dehydrogenase(MDH) and formate
      dehydrogenase(FDH) of A. auricula were respectively controlled by 7, 5 and 4
      polymorphic loci. The isozyme bands which were controlled by EST-3, EST-4, MDH-3
      and MDH-4 loci were stably expressed in the parental strains and most tested F1
      monokaryon strains. Genetic analysis was impossible for these four loci. The
      relative fitness between allele observed value and theoretical expected value was
      further examined by means of contingency chi 2 at 1% level, the result indicated
      that significant difference existed from the chi 2 value of MDH-5 and FDH-1 in 7
      polymorphic loci of EST, MDH and FDH, and denied the hypothesis in which the
      isozyme bands controlled by MDH-5 and FDH-1 loci were presumed to be allozyme
      bands. The allele observed values (100:SA) of EST-7, MDH-1, MDH-5, FDH-1, FDH-2
      and FDH-4 were significant deviation of theoretical expected ratio (1:1), which
      showed that these variations were not due to the allele expressions. The
      significant difference was not be showed at the 5% level from the chi 2 values of
      EST-1, EST-2, EST-5, EST-6 and MDH-2, this result indicated the allele
      segregation was corresponding to the theoretical expected ratio at these 5 loci,
      these 5 loci were allozyme loci which was corresponding to Mendel's law of
      segregation. A total of 10 possible pair combinations from the 5 allozyme loci
      were tested. The numbers of monokaryon strains with parental type zymogram or
      recombinant type zymogram were counted up, and the chi 2I, chi 2II and chi 2L
      were calculated for examining the linkage relationships of these allozyme loci,
      the chi 2L value attained to significant difference at 1% level between EST-5 and
      EST-6 loci, it indicated that the linkage relationship existed between the two
      loci, non-linkage relationships existed between the other pairing loci of 5
      allozyme loci.

PMID- 12812081
TI  - Phylogenetic relationships among citrus and its relatives as revealed by SSR
      markers.
AB  - Phylogenetic relationships among 29 accessions belonging to Citrus, Poncirus,
      Fortunella, Microcitrus, Eremocitrus, Atlantia and Severinia were investigated
      using SSR markers. Seven SSR primers generated 114 polymorphic alleles, with an
      average of 16.3 alleles per primer. Cluster analysis via neighbour-joining method
      showed that Microcitrus was close to Citrus; Poncirus was distant from Citrus,
      which suggested that Poncirus could not be derived from Citrus. High frequency of
      the homozygous SSR locus supported the species status of Fumin trifoliate orange.
      Separation of neither Papeda and Citrus nor Archicitrus and Metacitrus was well
      resolved. The present work confirmed citron, pummelo and mandarin as basic
      species of cultivated citrus since they could be placed into three distinct
      clusters.

PMID- 12812082
TI  - [Characterization of 5S rRNA gene sequence and secondary structure in
      gymnosperms].
AB  - In higher plants the primary and the secondary structures of 5S ribosomal RNA
      gene are considered highly conservative. Little is known about the 5S rRNA gene
      structure, organization and variation in gyimnosperms. In this study we analyzed
      sequence and structure variation of 5S rRNA gene in Pinus through cloning and
      sequencing multiple copies of 5S rDNA repeats from individual trees of five
      pines, P. bungeana, P. tabulaeformis, P. yunnanensis, P. massoniana and P.
      densata. Pinus bungeana is from the subgenus Strobus while the other four are
      from the subgenus Pinus (diploxylon pines). Our results revealed variations in
      both primary and secondary structure among copies of 5S rDNA within individual
      genomes and between species. 5S rRNA gene in Pinus is 120 bp long in most of the
      122 clones we sequenced except for one or two deletions in three clones. Among
      these clones 50 unique sequences were identified and they were shared by
      different pine species. Our sequences were compared to 13 sequences each
      representing a different gymnosperm species, and to six sequences representing
      both angiosperm monocots and dicots. Average sequence similarity was 97.1% among
      Pinus species and 94.3% between Pinus and other gymnosperms. Between gymnosperms
      and angiosperms the sequence similarity decreased to 88.1%. Similar to other
      molecular data, significant sequence divergence was found between the two Pinus
      subgenera. The 5S gene tree (neighbor-joining tree) grouped the four diploxylon
      pines together and separated them distinctly from P. bungeana. Comparison of
      sequence divergence within individuals and between species suggested that
      concerted evolution has been very weak especially after the divergence of the
      four diploxylon pines. The phylogenetic information contained in the 5S rRNA gene
      is limited due to its shorter length and the difficulties in identifying
      orthologous and paralogous copies of rDNA multigene family further complicate its
      phylogenetic application. Pinus densata is a diploid hybrid between P.
      tabulaeformis and P. yunnanensis. Its 5S rDNA composition is consistent with its
      hybrid origin. 5S rRNA of all gymnosperms published so far could be folded into a
      general secondary structure. Variation in this secondary structure was detected
      among species. About 55% of the 120 bp nucleotide positions was variable, in
      which 68% was on stem regions. Nevertheless, the positions at the end of the
      stems and those adjacent to loops are conserved. Their stability directly
      determines the size of the loops. Some mutations such as compensatory base-pair
      substitutions, and G-U pairing could be regarded as mechanisms for maintaining a
      stable secondary structure. The loops of the secondary structure are also
      relatively conserved. It seems that stable helices are necessary for the function
      of the gene. The conserved nucleotides in the loops are probably involved in the
      interaction with proteins and/or RNAs or with other nucleotide in the formation
      of the tertiary structure. However, unlike other reports, Loop E was found quite
      mutable among pines. These variations together with those on stems might be
      caused by the presence of pseudogenes among our clones. A preliminary evaluation
      indicates that only seven of 50 unique sequences are potentially functional
      genes.

PMID- 12812083
TI  - The heritability theory of heterosis and its meaning for global agriculture.
AB  - This paper begins with the overthrow of the concept of combining ability in
      crossbreeding by the concept of heritability. The reason is that general
      combining ability changes with the number and kind of pure strains in the
      foundation stock and hence special combining ability changes also, so that work
      with different kinds of pure strains in the foundation stock cannot be compared.
      Hence combining ability is useless as a parameter to predict the amount of
      heterosis expected in the next generation. On the other hand, since each cross
      has a separate heritability, it can be applied to a cross population just as
      successfully as in purebreeding. Since the same concept holds in both cases,
      resort to any other concept would be superfluous. That's why combining ability
      must be rejected. Another reason (not given in the full text) is, an infinite
      number of pure strains would be required in the foundation stock for its results
      to be comparable with those of the heritability theory, which disposes of its
      utility altogether. The main content of the thesis is then the centennial enigma
      of heterosis can be resolved by Descarte's theoretic method of deduction.
      Accordingly we start from the definition of heterosis. [formula: see text] where
      H is heterosis, F1 is the first generation offspring, MP is the mean of the
      parents or midparent, and from the use of a binomial random variable and its
      extension to the multinomial case derive the basic relations of heterosis with
      its components. Starting with second degree statistics, we obtain [formula: see
      text] where V and cov stand for variance and covariance. The equations of
      heterosis are [formula: see text] where N is number of genes controlling a trait,
      a = (Pi - Pj)/2, d is deviation from midparent, while the variance components are
      all indicated by their names under the respective terms. It turns out that all
      these can be easily computed from the data so that the problem becomes a simple
      one which any college student may solve. In other words, the right answers are
      found when the right questions are asked. Who had ever shown that the
      heritability principle is inapplicable in crossbreeding, e.g., in a crossing of
      two pure strains? From this cue arose the realization that the F1 of a cross of
      two pure strains must also be a Mendelian population, with p and q both equal to
      1/2 which simplifies the algebra outright. This Heritability Theory of Heterosis,
      or HTH in capital letters, rests on 2 initial arguments: 1) Since 0.5 + 0.5 = 1,
      crossing two pure strains gives a population which is only a special case of pure
      breeding, therefore a heritability coefficient must exist for the F1; 2) Our
      problem reduces to that of finding that coefficient; the answer is given by the
      additive component divided by VF1, i.e., (1/2) Na2/VF1. which is readily found
      from the solution of the heterosis equations. Thus the eternal enigma of
      heterosis is resolved! This happened at the end of the 20th century. We now come
      to the second point of the discovery, the new genetic parameter crossheritability
      which will rise in size with the increase of the number of times it's used and
      form the link between breeding and evolution. The advent of the Age of Evolution
      Engineering in the 21st century marks a totally new era, showing that artificial
      will ultimately supercede natural selection, with the long span of time element
      eliminated. For agriculture at least, it means there is no limit to the increase
      of food supply by the new method, with the concentration of desirable genes by
      hybridization in place of the old theory of their fixation. Genetic gain is
      achieved through artificial selection, with an 80% saving of time, labor and cost
      by adoption of the new method. Applied to a further increase in all kinds of
      agricultural products including hybrid rice, it means that a huge escalation, in
      fact a New Green Revolution, on a much larger scale than that of any such before,
      is in view, provided it is adopted in our research and educational institutions
      as early as possible, ere its spread elsewhere. The possibilities from the
      evolution point of view can only be pictured by science fiction.

PMID- 12812084
TI  - Expression research for human DDX36 and mouse Ddx36 gene in the adult testis.
AB  - Drosophila melanogaster is one of the most intensively studied organisms in
      biology and serves as a model system for structural and functional genomic
      research. With the strategy of homologue molecular cloning using the sequence of
      the maleless gene (mle) of Drosophila, the novel homologous human and mouse genes
      with longer DNA/RNA helicase box (DEAD/DEAH box), named, DDX36 and Ddx36 genes,
      respectively, were cloned as new members of the DEAD/H box superfamily. In order
      to further investigate the relationship between those two genes of DDX36 and
      Ddx36 and the role of spermatogenesis, the expression analysis of them have been
      performed by the techniques of Northern blotting, RT-PCR and tissue in situ
      hybridization. The result indicated that the DDX36 and Ddx36 gene has highly
      expressed in the adult testis. It was primarily suggested that DDX36 and Ddx36
      gene may be related with spermatogenesis.

PMID- 12812085
TI  - Expression of biologically active human tumor necrosis factor beta by
      Streptomyces lividans.
AB  - The production of human tumor necrosis factor beta (hTNF beta) in Streptomyces
      lividans was studied. The expression of hTNF beta uses the transcription,
      translation and secretion signals of subtilisin inhibitor VSI which is naturally
      produced by Streptomyces venezuelae CBS762.70. In direct secretory expression
      cassette, hTNF beta cDNA was fused 2 amino acids after the signal peptidase
      cleavage site. In fusion expression cassette, hTNF beta cDNA was fused after the
      total vsi gene. In intracellular expression cassette, hTNF beta cDNA was fused
      after initiation codon ATG. The expression cassettes were subcloned into
      Streptomyces multi-copy plasmid pIJ486 respectively and transformed into S.
      lividans TK24. The recombinant strains were designated as S. lividans (pIJ486
      hTNF beta), S. lividans (pIJ486-vsi-hTNF beta) and S. lividans (pIVPA-hTNF beta).
      The analysis of expressed proteins by Western blotting and biological activity
      measurements revealed hTNF beta was expressed by the recombinant strains with
      bioactivity. The molecular weight of directly secreted product is around 16 kDa,
      and the expression level at 48 hours in NB medium was 0.7 mg/L. Intact product
      could be obtained when hTNF beta was expressed intracellularly, although it may
      be degraded to lower molecular weight product when cultivation was prolonged. The
      intracellular expression level at 48 hours in NB medium was 25.1 mg/L.

PMID- 12812086
TI  - The effects of different donor cells and passages on development of reconstructed
      embryos.
AB  - In order to study the effects of different donor cells and passages on
      development of nuclear transfer embryos, we constructed embryos by electrofusing
      several kinds of donor cells into enucleated M II oocytes from Kun Ming (KM)
      mouse. These cells include 2-cell embryonic blastomeres, KMW embryonic stem (ES)
      cells, fetal fibroblast, ear fibroblast, tail tip fibroblast, sertoil cells and
      spermatogonia. Meanwhile, we compared the effects of passage numbers of fetal
      fibroblast cells on developmental competency after nuclear transfer. We found
      that 7.4% of reconstructed embryos from 2-cell embryonic blastomeres and 0.7%
      from ES cell could develop to blastocyst in vitro; embryos from fetal fibroblast
      could only develop to morula stage with the rate of 0.2%; embryos from
      spermatogonia could only develop to 8-cell stage and the rate was 0.3%; embryos
      respectively from ear fibroblast, sertoli cell and tail tip fibroblast could only
      develop to 4-cell stage. Although 2-cell development rate of embryos
      reconstructed from fetal fibroblast in first passage was significantly lower than
      those from the 2nd, the 3rd and the 4th passage, embryos from different passages
      could develop to 8-cell stage except the 3rd passage. The result indicated that
      it is more difficult for terminally differentiated cell nuclei to be reprogrammed
      in enucleated M II oocytes than for low differentiated cell nuclei. The reason of
      low development rate from ES cells maybe that most of ES cells was at S stage of
      the cell cycle, which out of coordination with M II oocytes. We could conclude
      that culture and passage of donor cells might be benefit to nucleus
      reprogramming.

PMID- 12812087
TI  - Polymorphism of E. coli F18 receptor gene in different pig breeds.
AB  - The genetic variation of E. coli F18 receptor(ECF18R) loci in 867 pigs including
      Large Yorkshire, Landrace, Duroc, Ningxiang pig, Shaziling pig and Daweizi pig
      was detected by PCR-RFLP with Hin6 I. The results showed as follows: The three
      exotic breeds including Large Yorkshire, Landrace and Duroc were proved to be
      polymorphic at the Hin6 I-RFLP site. The average susceptibility genotype
      frequency of AG and GG in the exotic breeds was 0.94, G allelic frequency was
      0.76. The C-->A mutation frequency at M307 site was very low in exotic breeds.
      The resistance genotype frequency of AA was 0.06. But the three native breeds
      including Ningxiang pig, Shaziling pig and Daweizi pig presented only GG genotype
      and no variation at the Hin6 I-RFLP site. The chi 2 value of ECF18R genotype
      distribution at the Hin6I-RFLP site in different pigs indicated that ECF18R
      genotype distribution of every exotic pig breed had significant or highly
      significant differences with three native pig breeds'. The ECF18R genotype
      distribution of three native pig breeds was the same completely. The others had
      no difference except that Landrace ECF18R genotype distribution had significant
      differences with Duroc's in the exotic breeds of pig.

PMID- 12812088
TI  - Genetic diversity of microsatellite loci in fifty-six Chinese native pig breeds.
AB  - The genetic diversity of fifty-six indigenous pig breeds in China, and three
      introduced pig breeds (Duroc, Landrace and Large White) was surveyed using twenty
      seven microsatellites recommended by the International Society for Animal
      Genetics (IS-AG) and Food and Agriculture Organization (FAO). By means of the
      allele frequencies, mean heterozygosity, effective number of alleles, estimator
      of gene differentiation, polymorphism information content, genetic distance and
      dendrogram analysis, the genetic variability and population structure of native
      pig breeds were estimated. Genetic variabilities within native pig breeds are as
      follows: Effective number of alleles vary from 2.12 to 9.03, from 0.44 to 0.87
      for mean heterozygosity, from 0.39 to 0.86 for polymorphism information content.
      Nei's genetic distance and Nei's standard genetic distance were estimated and
      used to construct UPGMA and NJ dendrograms, which were evaluated by the bootstrap
      test. Fifty-six Chinese indigenous pig breeds were clustered into twelve groups
      based on the dendrogram. Compared with the classification in Pig Breeds in China,
      I, II and III groups in the study are equivalent to North-China type, IV group
      basically accords with Lower-Changjiang River Basin type, V, VI, VII, VIII and IX
      groups quite correspond with Central-China type, X and XI group largely
      correspond to South-China type, the last group, XII is equal to South-west type
      at large. Suggestions that the conservation farms together with conservation
      areas are appropriate methods for the preservation of native pig breeds in our
      country were proposed. The results could provide basic molecular data for the
      research on the germplasm characteristics of local breeds in our country and
      scientific basis for the conservation and utilization of those breeds.

PMID- 12812089
TI  - Genetic differentiation of different populations of four locust species in China.
AB  - The genetic structure of eight populations of four locust species in three
      families (Catantopidae, Pamphagidae and Pyrgomorphidae) was examined by means of
      horizontal starch gel electrophoresis, the locusts were collected from Shanxi,
      Jiangsu and Hebei Province in China. The allele frequency and allozyme
      polymorphism of 12 enzymes (18 loci) were analyzed. Low variability with a few
      alleles was observed in Shirakiacris shirakii and Atractomorpha sinensis,
      however, Oxya Chinensis and Haplotropis brunneriana showed high polymorphism. In
      the eight populations of the four locust species, high percentage of polymorphic
      loci was observed (53.3%-100.0%). Owing to heterozygote deficiency of some
      species, all the four species demonstrated low overall heterozygosity (Ho = 0.034
      0.139), which lead to the genotype frequency deviated significantly from Hardy
      Weinberg equilibrium. However, many of the examined loci were fit for or close to
      H-W equilibrium in Atractomorpha sinensis. A certain differentiation in mean
      heterozygosity was found among the four species. Due to the difference of
      migratory capability, reproductive manner and living bound, mean heterozygosity
      (Ho) is higher in Haplotropis brunneriana (Ho = 0.089-0.139) and Oxya Chinensis
      (Ho = 0.073-0.090) than in Atractomorpha sinensis (Ho = 0.034-0.050) and
      Shirakiacris shirakii (Ho = 0.048-0.068). Genetic differentiation from F
      statistics was also different at population level among four locust species. It
      was high in Haplotropis brunneriana (Fst = 0.32) and Atractomorpha sinensis (Fst
      = 0.31), and low genetic differentiations were observed in Oxya Chinensis (Fst =
      0.20) and Shirakiacris shirakii (Fst = 0.18). It was confirmed that migratory
      capability, adaptability and surrounding factors had an important influence on
      the genetic differentiation of locust populations. The taxon relationships based
      on Nei's genetic identity (I) and genetic distance (D) were consistent with
      results obtained from karyotypic analyses. Oxya Chinensis and Shirakiacris
      shirakii in the same family have a higher genetic identity (I = 0.576) and a
      smaller genetic distance (D = 0.559); the species examined in Pampagidae
      displayed somewhat closer relationship to those in Pyrgomorphidae (D = 0.776, I =
      0.464) than to those in Catantopidae (D = 0.908, I = 0.406). It is suggested that
      the allozyme analysis is an useful molecular marker for phylogenetic
      reconstruction of locust at both species and population levels.

PMID- 12812090
TI  - QTL and epistatic interaction underlying leaf chlorophyll and H2O2 content
      variation in rice (Oryza sativa L.).
AB  - It is meaningful to study the genetics of the traits associated with
      photosynthesis such as leaf chlorophyll and H2O2 contents for high yield breeding
      in rice. A mapping population of 98 BC1F9 lines (backcross Inbred Lines, BIL),
      derived from a backcross of Nipponbare (japonica)/Kasalath(indica)//Nipponbare by
      the single-seed-descent methods, was employed to map quantitative trait loci
      (QTL) underlying such rice traits as leaf chlorophyll and H2O2 contents. Five and
      two QTLs were detected for leaf Chlorophyll and H2O2 content variation,
      respectively. Among the QTLs detected, q-Chl1 on chromosome 1 accounted for 22%
      variation for leaf chlorophyll content variation. The alleles from Nipponbare
      increased stature at the locus; On the other hand, q-H2O2(1) which associated
      with H2O2 content was also located on the same region as q-Chl1. The alleles from
      Nipponbare decreased stature at this locus. The 2 traits have the 2 QTL sharing
      the same chromosome locations, which was located between C86 and C813 on
      chromosome 1. Epistasis analysis showed QTL with interaction distributed on
      chromosome 2, 6, 11 and 12. However, no QTL interacted with q-Chl1 or q-H2O2(1)
      was detected. It can be deduced that alleles from Nipponbare at the region
      between C86 and C813 on chromosome 1 increases leaf chlorophyll content and
      decreases H2O2 content at the mean time with significant additive effect but
      little epistasis.

PMID- 12812091
TI  - Mapping quantitative trait loci underlying appearance quality of rice grains
      (Oryza sativa L.).
AB  - Ninety-eight backcross inbred lines (BILs) derived from a subspecific cross of
      Nipponbare (japonica)/Kasalath (indica)//Nipponbare and its genetic linkage map
      were used to identify quantitative trait locus (QTL) controlling rice appearance
      quality traits such as grain length (GL), grain width (GW), length-width ratio
      (LWR), percentage of grains with chalkiness (PGWC), square of chalky endosperm
      (SCE), degree of endosperm chalkiness (DEC) and grain endosperm transparency
      (GET) by composite interval mapping over two years. A total of 33 QTLs were
      identified to be significant in at least one year for seven traits and the number
      of QTL for each trait ranged from four to seven, showing that appearance quality
      of rice grains were controlled by multigenes. The phenotypic variation explained
      by individual QTLs ranged from 6.2% to 15.2% for GL, 8.3% to 32.5% for GW, 6.8%
      to 19.8% for LWR, 6.4% to 28.5% for PGWC, 6.1% to 16.9% for SCE, 9.3% to 17.2%
      for DEC, and 5.6% to 25.2% for GET. The distribution of QTL were characterized by
      clustering with the intervals of C1488-C563 on chromosome 3, R830-R3166 and R1436
      R2289 on chromosome 5, R2147-R2171 on chromosome 6 each harboring over 3 QTLs.
      The QTL-by-environment interactions were observed by comparing QTL mapping of the
      same population grown in 2 consecutive years, but were trait dependent. The QTL
      for GL and LWR were rather stable across years while that for PGWC, SCE and DEC
      were very sensitive to environments.

PMID- 12812092
TI  - Relationship between differences of gene expression in early developing seeds of
      hybrid versus parents and heterosis in wheat.
AB  - In order to understand molecular basis of heterosis, mRNA differential display
      was used to analyze the differences in gene expression between seeds of 18
      reciprocal hybrids and their 6 parents at 6th day after pollination. The
      relationship between gene expression patterns and heterosis was determined. Only
      bands that can be repeated in duplicate PCR were used for analysis so as to
      reduce false positive bands. Among the total of 2,025 bands displayed, 1,386
      bands (68.43%) were reproducible. Eight patterns (fifteen kinds) of gene
      expression were observed, which include: (1) bands occurring in only one parent
      (two kinds); (2) bands observed in both hybrids and one parent (two kinds); (3)
      bands detected in parents and one hybrid (two kinds); (4) bands displayed in only
      one hybrid (two kinds); (5) bands revealed in one hybrid and its corresponding
      female (two kinds) or male (two kinds) parent; (6) bands visualized in only both
      hybrids (one kind); (7) bands occurring in only parents (one kind); (8) bands
      observed in parents and both hybrids (one kind). Our results indicate that
      differences of gene expression between hybrids and their parents are very
      obvious. The percentages of bands observed in only both hybrids and in only both
      parents are lower. The analysis shows that bands observed in parents and both
      hybrids are not correlated with all nine agronomic traits, which indicates
      differentially expressed genes are mainly responsible for the observed heterosis.
      At least one pattern of differential gene expression is significantly correlated
      with nine agronomic traits. Silenced bands in hybrid (which include bands
      occurring in only one parent, bands detected in both parents and one hybrid and
      bands in only parents) and bands present in one hybrid and its corresponding
      female or male parent are likely to play important roles in heterosis. These
      results suggest that early seed development could be closely related to
      heterosis.

PMID- 12812093
TI  - Molecular marker analysis and genetic basis for sterility of typical
      indica/japonica hybrids.
AB  - To explore the genes differentiated between typical indica and japonica
      varieties, two typical indica/japonica varieties, Balilla (japonica) and Nantehao
      (NTH, indica), were selected to construct genetic populations based on the widely
      surveying for spikelet and pollen fertility of 90 indica/japonica F1 hybrids,
      which also were used as the wide compatability testers. In order to analyze the
      genes (QTLs) related to spikelet and pollen fertility, two reciprocal backcross
      populations Balilla/NTH//Balilla and Balilla/NTH//NTH were constructed and the
      spikelet and pollen fertility of each individuals were assessed. In both
      populations, two traits all appeared distorted normal distribution, but in the
      first population, they forwarded to low-level fertility type, the later
      population, forwarded to high-level fertility type relatively. The results
      indicated that both of male and female gametophytes of Balilla/NTH hybrids were
      partial sterile. Then we analyzed the SSR marker genotype of each individuals of
      Balilla/NTH//Balilla population containing 142 individuals, and constructed a SSR
      linkage map, in which, there were 108 information markers distributing on all 12
      chromosomes equably, average marker distance was about 11.9 cM. Therefore the
      linkage map was qualified for QTL analysis. Two methods were employed to conduct
      QTLs analysis, i.e., single marker analysis and interval mapping. According to
      single marker analysis, 17 and 12 markers were found significantly responsible
      for spikelet and pollen fertility, respectively. And further study by means of
      MAPMAKER/QTL software, for spikelet fertility trait, two QTLs were detected,
      qSPTF1 on chromosome 1 and qSPTF6 on chromosome 6, and their additive effect were
      13.501 and -16.414, respectively. According to previous studies, qSPTF6 was
      deduced to be the same locus as S-5. For pollen fertility, qPLLN7 on chromosome 7
      and qPLLN9 on chromosome 9 were detected, and their additive effects were -12.003
      and -11.012, respectively. Because the QTLs detected cannot explain completely
      the total variance of mapping population, other genetic factors must be existed
      to be responsible for spikelet and pollen partial sterility. Hence we let two
      random markers as putative covariates, and divide the 142 individuals into four
      groups according to the two marker genotypes, then the average values of spikelet
      and pollen fertility of each groups were calculated for two-way ANOVA (analysis
      of variance). The results indicated that there existed strong interaction for
      both spikelet fertility and pollen fertility. At a significance level of 0.005,
      there over 61 and 51 pairs loci interactions detected playing an important role
      in spikelet and pollen sterility expression, respectively. These results
      indicated that epistasis also was one of major genetic components controlling
      indica/japonica hybrid sterility.

PMID- 12812094
TI  - Expression analysis of orf77 and R region in mitochondrial DNA of S-type CMS
      maize.
AB  - It is generally recognized that S type of CMS in maize associated with the
      recombination region R in mitochondria. Complicated DNA recombination and changes
      of transcripts of R are observed in several subgroups of S cytoplasm. R region
      includes two open reading frames (orf355 and orf77) and they are all chemeric.
      Among the sequence of orf77, there are three stretches similar to atp9 of
      mitochondria. Many different S cytoplasms are found in maize in China and
      researches on them show that similar R region and sequence are also found in the
      mitochondrial DNA in Tangxu, Shuang and J (cytoplasm. Northern analysis of
      Tangxu, J cytoplasm with Probe R and orf77 indicates that orf77 co-transcribes
      with R region and the nuclear restorer gene Rf3 affects their expression. In all
      tested S cytoplasm plants with the genotype of s-rf3rf3, both probe orf77 and R
      can detect six transcripts of 2.8, 1.6, 1.1, 0.9, 0.7 and 0.4 kb. In the presence
      of the nuclear restorer-of-fertility gene Rf3, previous transcripts of 2.8 kb and
      1.6 kb are disappeared, but the other four transcripts are not changed. In T and
      C cytoplasm of CMS, only four transcripts of 1.1, 0.9, 0.7 and 0.4 kb appear when
      hybrid to probe R. Further Northern analysis of probe atp9 proved that all the
      four transcripts of 1.1, 0.9, 0.7 and 0.4 kb were actually transcripts of gene
      atp9, so only the transcripts of 2.8 kb and 1.6 kb are particular to R region of
      S. In addition, atp9, atp6 and cox II each has the same transcription pattern in
      tassel with different genotypes respectively. It can be included that R region
      and orf77 are the most important candidate gene for S-CMS.

PMID- 12812096
TI  - [Metastatic prostatic cancer].

PMID- 12812095
TI  - Isolation and characterization of a carboxylic transport protein JEN1 and its
      promoter from Metarhizium anisopliae.
AB  - Based on the flanking sequence of T-DNA of a T-DNA insertion mutant of Beauveria
      bassiana, T12, the full length cDNA of carboxylic transport protein, designated
      MaJen1, was cloned from Metarhizium anisopliae. MaJen1 is 1,695 bp long and
      contained a 1,524 bp ORF which predicted a protein of 508 amino acid. The amino
      acid sequence of the gene showed 69% and 31% identity to the carboxylic transport
      protein of Neurospore crassa and Saccharomyces cerevisiae, respectively. The
      genome sequence, GMaJen1, was amplified by PCR, indicating that there were two
      introns in GMaJen1. Southern analysis indicated that GMaJen1 was present as a
      singl copy in Metarhizium anisopliae. The result of RT-PCR showed that expression
      of MaJen1 was induced by the cuticle of cockroach and repressed by glucose. A
      1,626 bp upstream sequence of GMaJen1 was amplified by YADE method, which
      contained several putative binding domains of glucose repressor.

PMID- 12812097
TI  - [Medullary compression in men with prostatic cancer. A retrospective study of
      medical records].
AB  - INTRODUCTION: The aim of the study was to describe symptomatology and prognosis
      in patients with spinal cord compression and prostate cancer. MATERIAL AND
      METHODS: The material was retrospective and included patients from 1.1.1996 to
      31.12.2000 with compression of the medulla, dura or intraspinal roots. Data
      collection was concluded on 30.6.2001. RESULTS: Seven patients had the cancer
      diagnosis at the time of the intraspinal compression. The most frequent debut
      symptom was acceleration of pain, two thirds had neuropathic pain, and three
      patients were free of pain. Paresis was present in 23 patients and 18 had sensory
      symptoms. External irradiation was given to 29 patients, three had a
      neurosurgical procedure and irradiation and two patients had just endocrine
      manipulation. The treatment result was good or moderately good on pain in three
      fourths of the patients, and on the neurological symptoms in two thirds. Eight
      patients had recurrence. Median survival was three months for patients with
      hormone resistant progression and two years for those patients, who got their
      cancer diagnosis in connection with the intraspinal compression. CONCLUSION:
      Rapid acceleration of pain is an early symptom of intraspinal compression.
      Morphine-resistant pain or neuropathic pain and neurologic symptoms are typical
      findings, but none of the symptoms are obligatory. Early acute treatment may give
      good recovery and the survival is comparable with the survival of patients whose
      illnesses are in the same stadium but who do not suffer from intraspinal
      compression.

PMID- 12812098
TI  - [The effect of bisphosphonates on pain relief in patients with bone metastases: A
      status article based on the Cochrane analysis: "Bisphosphonates for the relief of
      pain secondary to bone metastasis"].

PMID- 12812099
TI  - [Assisted home care of patients with exacerbation of chronic obstructive
      pulmonary disease. Earlier discharge to treatment, monitoring and care at home
      led by a respiratory nurse].
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of
      hospitalisation in Danish adults, and admission rates are expected to increase in
      the future. Assisted home care with disease monitoring and treatment by a
      pulmonary nurse may reduce time spent at hospital and the economic burden of
      COPD. In order to evaluate various types of assisted home care, the selection of
      patients, feasibility, effect, safety, and cost-effectiveness, the literature was
      reviewed. Most information is available on assisted home care following a
      hospital-based assessment and led by a respiratory nurse. According to the
      literature, assisted home care is a well tolerated, safe, and economic
      alternative to hospital admission for about 25-30% of the patients referred to
      hospital due to exacerbation of COPD. We recommend that assisted home care is
      tested in Denmark.

PMID- 12812100
TI  - [Thermography: a hot trail in the search for the vulnerable atherosclerotic
      plaque?].
AB  - Vulnerable atherosclerotic plaques are characterised by a large lipid core and a
      thin fibrous cap infiltrated with activated inflammatory cells. Heat is a
      cardinal sign of local inflammation, and atherosclerotic lesions display thermal
      heterogeneity, with increased temperature being correlated with inflammatory cell
      density, unstable clinical presentation, and unfavourable outcome after
      percutaneous interventions. Thermography is a promising new technique for
      assessment of atheroclerotic plaque composition.

PMID- 12812101
TI  - [Validation of Doppler ultrasonographic scanning for the detection of stenoses in
      peripheral vascular reconstructions].

PMID- 12812102
TI  - [Interobserver variation in ultrasonographic scanning of carotid stenosis].
AB  - INTRODUCTION: Ultrasonic carotid interna scanning is today the gold standard for
      diagnosing carotid stenosis in patients with stroke or transient ischemic attack.
      The procedure of ultrasonic carotid interna scanning is not a well-defined
      procedure. Knowledge of the reproducibility of the method used in own department
      is important in order to evaluate its usefulness. MATERIAL AND METHODS:
      Interobserver variability of ultrasonic, duplex carotid artery scanning was
      examined in 68 carotid arteries in 35 patients by two experienced technologists.
      The two observers were compared using the kappa (kappa) statistics to analyse the
      agreement beyond chance. RESULTS: kappa was 0.70 (CI: 0.56-0.83) when the
      stenoses were categorised in the intervals 0-14%, 15-49%, 50-69%, 70-79%, 80-99%
      and occlusion. Categorising the stenosis in the clinically relevant intervals 0
      69%, 70-79% and occlusion which are used to determine if the patient is a
      candidate or not to carotid endarterectomy yielded a kappa = 0.92 (CI: 0.81
      1.00). DISCUSSION: Low level stenosis accounted for most variability. If state-of
      the-art ultrasonic equipment and experienced technologists are used a high level
      of reproducibility can be achieved.

PMID- 12812103
TI  - [Urological training in the county of Roskilde].
AB  - INTRODUCTION: Training in surgical skills and the importance of function-bearing
      units are the subject of much debate at the moment. An exposition is given of the
      quality of the urological training in the County of Roskilde, which corresponds
      to a function-bearing unit as to size. MATERIAL AND METHODS: The exposition is
      based on charts of specific oncological diagnoses during one year and the list of
      operations performed by phase III interns during a period of six months. RESULTS:
      The number of operations performed by phase III interns during the two periods in
      compared with the informal claims of The Danish Urological Society. DISCUSSION:
      As regards open surgery, the number of operations performed by phase III interns
      fully lives up to the informal requirements of the Danish Urological Society and
      the number of operations per intern exceeds what has previously been calculated
      at branch-specialized departments. The number of endoscopic operations was a
      little lower than expected and did not quite live up to the requirements. It is
      concluded that the urological training at a county urological department meets
      the requirements of the Danish Urological Society.

PMID- 12812104
TI  - [Are the Danish Society of General Practitioners' clinical guidelines concerning
      "Identification and investigation of dementia and dementia-like conditions"
      useful as the basis of dementia investigation in general practice?].
AB  - INTRODUCTION: During the last five years better possibilities have appeared for
      investigation and medical treatment of dementia. Society and the national health
      authorities have a growing demand for systematical identification of dementia. In
      1999, DSAM published a clinical guideline for identifying dementia. The aim of
      the study was to test the usefulness of that guideline. MATERIAL AND METHODS: A
      total of 22 out of 29 general practitioners (GPs) agreed to use the guidelines of
      the Danish Society of General Practitioners (DSAM) and the questionnaires from
      three consultations in order to systematically identify dementia. At the same
      time, the GPs gave their opinion about the usefulness of the guidelines. RESULTS:
      A total of 22 GPs sent results from 69 patients. A group of 49 patients had been
      CT-scanned, 13 patients had been examined by neuropsychologists, and nine
      patients had started acetylcholinesterase inhibitor treatment. CONCLUSION: Some
      GPs found it embarrassing to offer dementia identifying to their patients.
      Identifying dementia was complicated and time-consuming. Identifying dementia
      offered opportunities to look further into polypharmacy and cooperation with
      other health sectors. Necessary but not sufficient preconditions for starting
      identifying dementia in general practice will be fees, direct admission to CT
      scanning and neuropsychologist, and possibly right to prescribe
      acetylcholinesterase inhibitors. The conclusion was that all GPs found the
      guidelines of DSAM useful for identifying dementia in general practice.

PMID- 12812105
TI  - [Severe pre-eclampsia and fetal trisomy 13 in a multiparous woman].
AB  - Preeclampsia (PE) is a common clinical syndrome often seen in nulliparae and a
      major cause of maternal and neonatal morbidity and mortality. Genetic
      predisposition and abnormal trophoblastic function may contribute to the
      pathophysiology of PE. The association between trisomy 13 and PE might be
      suggestive for a causative effect of some fetal genes encoded on chromosome 13,
      predisposing for the development of PE. We here report a case of severe PE in a
      multiparous woman carrying a trisomy 13 fetus.

PMID- 12812106
TI  - [Poisoning with Aconitum napellus (monkshood)].
AB  - A lethal case of aconite poisoning due to ingestion of pieces of monkshood
      (Aconitum napellus) is described.

PMID- 12812107
TI  - [Targeted therapy with imatinib has reformed the treatment of chronic myeloid
      leukemia].

PMID- 12812109
TI  - [Stem cells one more time!].

PMID- 12812108
TI  - [Yes to stem cells].

PMID- 12812110
TI  - [Quality in general practice].

PMID- 12812111
TI  - [Evidence--human acknowledgement--the good physician--and the Ugeskrift].

PMID- 12812112
TI  - [When breast feeding was accused].

PMID- 12812113
TI  - [Inflammatory pathology in urology. Standardization].
AB  - The recognition, identification and management of the many events taking place in
      relation to an inflammatory response has become a rapidly growing field in
      medicine over the last few years. In this sense, the progress made in later years
      in the study of the molecular and cellular mechanisms of tissue inflammatory
      reactions in sites such as synovial membranes, gut mucosa, vascular endothelium
      etc, is considered highly relevant. A number of authors conscious of such events
      work on the standardization of clinical models of the inflammatory responses of
      genitourinary organs resulting from the action of a variety of harmful events.
      This review is warranted by the prevalence and morbidity and mortality of
      inflammatory conditions, as well as the complex work of incorporating to Urology
      the findings from other Biomedical Sciences.

PMID- 12812114
TI  - [The Internet in medicine. A help, a problem, a cause of errors...?].
AB  - The Internet has been a breakthrough for Professional Medical Training. Medline
      databases are increasingly being used by the scientific community at large.
      Patients have also started to use the Internet as a source of information on
      their illnesses, and look in the web for a second opinion. This paper shows the
      advantages derived for the patients from using the Internet as well as the risks
      involved from a poorly understood, even not scientifically validated information.
      The Urology Associations themselves should take responsibility of the web sites
      in a unambiguous way, by including evidence-based medicine, offering assistance
      to those patients who want to compare their specialist's opinion with that
      obtainable in the Internet, and with the doctors themselves directing those who
      show a real interest to the most suitable web sites.

PMID- 12812115
TI  - The possible macrophage role in seminal fluid.
AB  - The present report was designed to study the macrophage role and their
      association with percentage of spermatozoa showing DNA native, morphologically
      normal sperm and occurrence of antibody-coated spermatozoa. Human sperm samples
      from 31 patients were used in this study. All samples were evaluated for standard
      semen parameters according to World Health Organization criteria. The sperm heads
      with abnormal versus normal chromatin structure were specified as orange-red
      versus green by Acridine Orange method. Macrophage concentration was assessed
      with Neutral Red in Neubauer hemocytometer. The technique for the determination
      of sperm bound antisperm antibodies was sperm mixed antiglobulin reaction. In our
      study the presence of antisperm antibodies in associated to macrophages
      concentration (p < 0.05). The log of phagocytic cells were highly correlated with
      an increase of spermatozoa showing DNA denaturation (p < 0.05). The log of
      phagocytic cells were highly correlated with an increase of spermatozoa showing
      DNA denaturation (p < 0.05). There isn't significative association between the
      log macrophage concentration and morphologically normal sperm (p: 0.414). Thus,
      the present study further emphasizes the importance of immunosurveillance of the
      macrophages, and the contribution at the semen quality for the success of the
      fertilization.

PMID- 12812116
TI  - [Ureteral stenosis after kidney transplantation: treatment with a self-expanding
      metal prosthesis].
AB  - OBJECTIVE: To determinate the efficacy in the treatment of ureteral estenoses
      after renal transplantation with metallic self-expandable stent. MATERIALS AND
      METHODS: From october of 1995 to april of 2002, 8 ureteral obstruction post renal
      transplantation have treated by means of implants of a metallic self-expandable
      stent (6 men and 2 women). The average time of pursuit was of 30 months (rank 2
      53 months). In this work the severity and location of the estenosis are analysed,
      the method of implant of the stent, the permeability of the same one, the levels
      of creatinine pre and postimplant and the complications derived from the same
      one. RESULTS: The treatment was effective in the 100% of the patients (8/8), with
      an average reduction of the creatinine of 36% (rank 13.6%-59.6%). The
      complications were minimum and the hospital stay was short. CONCLUSIONS: In the
      patients with: chronic deterioration of the graft with short functional
      expectation, patient with high surgical risk and reestenosis after ureteral
      reimplantation by previous ureteral estenosis, the use of a metallic self
      expandable stent, constitutes technique of election given its efficacy and low
      associate morbidity.

PMID- 12812117
TI  - [Pilot study of coadjuvant treatment of recurrent cystitis in women by means of
      AM3 (Immnoferon)].
AB  - OBJECTIVES: The aim is to evaluate the effectiveness of AM3 (Inmunoferon) in the
      treatment of the recurrent cystitis in women in order to know the rate of good
      results, previously to design a clinical trial. MATERIAL AND METHODS: Twenty-four
      women who had been diagnosed of two cystitis episodes in the previous 6 months
      without cure by antibiotic treatment were admitted to the study. Standard
      antibiotic treatment and 3 daily grammes of AM3 was given for 9 months. Infection
      and irritative symptoms during micturition rate were evaluated at the inclusion
      date and afterwards, at the first, third, sixth and nineth month. RESULTS:
      Nineteen patients finished the study. The infection rate decreased from 100% at
      the inclusion date to 26% in the first month and then it became stable about 50%.
      Irritative symptoms during micturition decreased from 46% at the inclusion date
      to a rate lower than 10% in the 4 controls running. CONCLUSION: AM3 reduced
      evident urinary infection in a 50% and irritative symptoms during micturition in
      a 90%. Control clinical trials are needed to confirm the AM3 effects on this
      pathology.

PMID- 12812118
TI  - [Finasteride: 10 years of clinical use. Systematic review of the literature].
AB  - INTRODUCTION: After ten years of clinical use of Finasteride in patients with
      BPH, we carried out a systematic review of the literature including the
      assessment of their quality and grading the level of evidence for clinical
      recommendations. METHODS: Using Medline, Embase, Healthstar and Cochrane Library
      from 1990 until 2002, we select all the studies referring patients between 50 to
      85 with symptoms of BPH, metrics of flow, prostatic volume, postmictional
      residue, detrusor pressure, adverse effects, cost-effectiveness and quality of
      life. RESULTS: We found out 135 references, of which 36 accomplish the inclusion
      criteria. Of those, 3 have got level I of evidence, 12 level II, 6 level III and
      10 level IV. Three are economic studies and two evaluate the quality of life.
      DISCUSSION: With a high level of evidence and after ten years of clinical use,
      Finasteride shows its effectiveness in reducing the symptoms of patients with
      prostate bigger than 40 ml and/or PSA of more than 1.4 ngr/ml, with scarce
      adverse effects with a clear improvement of quality of life. Therefore, it is
      recommended (grade A) for clinical use. CONCLUSIONS: Finasteride, through
      prostate volume reduction, modify natural evolution of BPH, decreasing the risk
      of acute urine retention and surgery.

PMID- 12812119
TI  - [Modified technique for transurethral resection of the prostate with suprapubic
      drainage and local anesthesia].
AB  - PURPOSE: To establish a technique for transurethral resection of the prostate
      (TURP), combining the use of local anaesthesia with an Amplatz suprapubic tube,
      in patients at high surgical risk. MATERIALS AND METHOD: A study was carried out
      in 32 patients who underwent TURP with a 30 F Amplatz suprapubic tube following
      local anaesthesia. This technique was indicated where surgery presented a general
      risk, in elderly patients, and for patients refusing to undergo spinal intradural
      or general anaesthesia. The mean age of the patients was 70 years (61-82 years).
      The risk of surgery was assessed according to the ASA classification. RESULTS:
      According to the ASA classification, 7 patients were ASA III (21.9%), and 25
      patients were ASA IV (78.1%). In 31 of the 32 patients the operation was
      completed in one session. When questioned about the pain they felt, 11 patients
      reported no pain, 12 slight discomfort and 3 occasional pain. In the latter three
      patients, intravenous sedation was enhanced with 0.1 mg etomidate per kg body
      weight. The volume of the resected fragments ranged from 18 to 120 ml, with a
      mean of 47 ml, except in one patient with 205 ml who required two treatment
      sessions. CONCLUSIONS: Large prostate resection in patients at high surgical risk
      was performed comfortably using a combination of local anaesthesia and an Amplatz
      suprapubic tube. This procedure is one possible option to be considered as an
      alternative to other treatments.

PMID- 12812120
TI  - [Adrenal ganglioneuroma. Report of a new case].
AB  - Ganglioneuroma is a benign neoplasm arising from neural crest tissue and is
      composed of mature ganglion cells and Schwann's cells. Most ganglioneuromas arise
      in the posterior mediastinum followed by the retroperitoneum. Only a small
      proportion of ganglioneuromas are adrenal in origin and occur most commonly in
      children and young adults. Characteristically, ganglioneuromas do not secrete
      excess catecholamines or steroid hormones, and they are usually clinically silent
      lesions incidentally detected in imaging studies for unrelated reasons. Because
      it is an uncommon lesion, adrenal ganglioneuromas is not included in the
      differential diagnosis of adrenal incidentalomas in adults. We presents a new
      case of a 6.5 cm adrenal ganglioneuroma incidentally diagnosed in a 50-year old
      male patient. The exeresis of the adrenal mass and pathohistological study
      confirmed the diagnosis.

PMID- 12812121
TI  - [Paratesticular dermoid cyst. Report of a case and review of the literature].
AB  - It is discussed a dermoid cyst case that depends on paratesticular structures,
      clinical entity which has low frequency of presentation. It is analyzed the
      controversial terminology of this tumours and are established anatomopathological
      criteria for this disease.

PMID- 12812122
TI  - [Traumatic intrathoracic herniation of the left kidney].
AB  - The detection of a intrathoracic kidney is an exceptional discovery. There is a
      large period of time between the injury and its clinical presentation revising
      the literature, so it is possible that the herniation of the kidney into the
      chest was caused by a rise in intra-abdominal pressure but going through a
      preexistent congenital way not caused by the traumatism. In order to dismiss this
      possibility and to prove the traumatic origin of the diaphragmatic rupture,
      surgeons have examined the intraoperative characteristics of the rupture's
      borders. The elevation of the kidney has been said to be progressive because of
      the positive intra-thoracic pressure and the negative intra-abdominal one. Our
      objective is to report an extraordinary case of abdominal traumatism whose clinic
      and radiological proofs let us get a rapid diagnosis and surgical demonstration
      of the direct herniation of the left kidney into the chest through a
      diaphragmatic rupture caused by the same traumatism.

PMID- 12812123
TI  - [Hyperplasia of adrenal rests in the testicle: a rare cause of male infertility].
AB  - We report the case of a 37-year-old man with infertility caused by bilateral
      testicular masses secondary to congenital adrenal hyperplasia (21-hydroxylase
      deficiency). Testicular biopsy was done and its was initially interpreted as
      Leydig cell tumor but after clinical information was histologically reclassified
      as tumor of the adrenogenital syndrome. The differential diagnosis with Leydig
      cell tumor is discussed and it must be established through the clinical,
      biochemical, radiological and pathological features.

PMID- 12812124
TI  - [Giant stone in a Bricker urinary diversion. Obstruction uropathy as the
      presenting form].
AB  - Bowel is used in urological surgery to replace the bladder, either as a conduit
      to drain urine to the abdominal wall as a urinary stoma or refashioned to form a
      substitute bladder. Many factors contribute to stone formation, being urinary
      stasis, mucus production and bacteriuria the most important. Metabolic changes
      induced by exposure of segments of the alimentary tract to urine promote
      struvite, calcium oxalate and calcium phosphate stone formation. Generally, the
      majority of patients with stones in a urinary diversion can be treated with
      minimally invasive techniques. Open surgical removal is considered when other
      modality of treatments cannot be accomplished safely and expeditiously.

PMID- 12812125
TI  - [Vesico-uterine fistula, a rare complication of cesarean section].
AB  - We present the case of a vesicouterine fistula secondary to a caesarean section
      indicated due to the disproportion the pelvis and the head of the baby. This kind
      of fistula is due fundamentally to obstetric causes, especially to caesarean
      sections in developed countries and to prolonged labour in developing countries.
      The commonest clinical presentation is urinary incontinence in the form of
      continuous or intermittent urinary leaks. Surgical treatment is generally the
      therapy of choice, although, in the case of small fistulas, conservative
      treatment is feasible. The best form of prevention is correct indication of
      caesarean section and careful surgical technique.

PMID- 12812126
TI  - [Metastatic tumors in the penis].

PMID- 12812127
TI  - Greek philosopher Heraclitus pronounced this immortal phrase.

PMID- 12812128
TI  - Combined effect of vestibular and craniomandibular disorders on postural
      behaviour.
AB  - A correlation has been reported in the dental literature between
      temporomandibular disorders and musculoskeletal abnormalities, however, the
      question whether they modify body postural sway remains controversial. In the
      present investigation, the Craniomandibular Index was used to evaluate the
      clinical extension of temporomandibular joint dysfunction and related problems in
      40 patients with normal vestibular function and in 42 patients with peripheral
      vestibular disorders. Balance function was assessed by static posturography and
      body sway area was measured in two conditions: i) eye open, and g) eye closed.
      Data were compared to those of 40 healthy subjects. Postural control showed a
      significantly different behaviour between groups with an increase in average body
      sway in patients with craniomandibular disorders as opposed to controls (p <
      0.005). Although the involvement of the stomatognathic apparatus was not
      quantitatively different in the two groups of patients, those also presenting a
      peripheral vestibular disorder exhibited greater average body sway than patients
      with only craniomandibular disorders (p < 0.005). The latter showed a greater
      average body sway than controls only in the trial with eyes closed (p < 0.05).
      The results demonstrated that craniomandibular alterations could produce moderate
      postural instability in patients with a normal vestibular function. Conversely,
      their association with peripheral vestibular disorders becomes a real challenge
      to the upright quiet stance probably due to a negative effect of somatosensory
      origin on the vestibulo-spinal reflex impairment.

PMID- 12812129
TI  - "Step by step" treatment of lateral semicircular canal canalolithiasis under
      videonystagmoscopic examination.
AB  - Aim of the work was to describe a new physical therapeutic approach for benign
      paroxysmal positional vertigo determined by canalolithiasis of the lateral
      semicircular canal. A review is made of the literature, and personal experience
      is reported. A total of 55 cases were observed, 40 geotropic forms, 15
      apogeotropic forms. Liberatory manoeuvres were carried out observing the
      nystagmus during videonystagmoscopic examination, thus attempting to solve the
      problem in the first treatment session. Monitoring the patient under
      videonystagmoscopic examination, progression of the otolithic mass towards the
      non-ampullary segment is documented by the appearance of a nystagmus directed
      towards the healthy side (and, therefore, inhibitory, due to ampullofugal
      deflection of the ampullary cupula) during the individual steps of the
      rehabilitation treatment. Of the 40 geotropic forms, 30 were successfully treated
      with the Vannucchi-Asprella technique, and the other 10 with the Vannucchi
      Asprella manoeuvre followed by a Lempert barbecue rotation. Of the 15
      apogeotropic forms, 6 were solved with the Vannucchi-Asprella manoeuvre, 2 with
      the Vannucchi-Asprella technique followed by Lempert, 6 with the inverted Gufoni
      technique, followed by Lempert, 1 transformed into geotropic with inverted Gufoni
      plus Lempert and then resolved by means of a Vannucchi-Asprella manoeuvre. In all
      cases, therapeutic success was achieved in the first session. Treatment of benign
      paroxysmal positional vertigo of the lateral semicircular canal does not allow
      every case to be fully solved at the first attempt with any technique proposed up
      to now, in particular, for the apogeotropic forms. Being aware of the different
      techniques, choosing that most appropriate for the patient's "physical" needs,
      and, above all, verifying under videonystagmoscopic examination the progression
      in an ampullofugal direction of the otolithic mass during treatment enable
      excellent therapeutic results to be obtained in the treatment of benign
      paroxysmal positional vertigo of the lateral semicircular canal, by modifying the
      rehabilitation strategy while it is being carried out. Videonystagmoscopic
      examination monitoring of the nystagmus during treatment of benign paroxysmal
      positional vertigo of the lateral semicircular canal, is taking the place of the
      rigid schematism of the manoeuvres proposed, so far, allowing the treatment
      programme to be adapted to the individual case, thus enabling a solution to be
      reached in the first rehabilitation session by means of tailored therapy.

PMID- 12812130
TI  - Newborn hearing screening by transient evoked otoacoustic emissions: analysis of
      response as a function of risk factors.
AB  - Hearing loss can be considered as the most common birth defect. Early detection
      of hearing loss by screening at, or shortly after, birth and appropriate
      intervention are critical to speech, language and cognitive development. In the
      present study, the characteristics of Transient Evoked Otoacoustic Emissions have
      been evaluated as a function of known pre- and perinatal risk factors for hearing
      loss. All newborns were screened for hearing loss using a physiologic test of
      hearing function, the Transient Evoked Otoacoustic Emissions. A total of 532
      consecutive newborn infants received binaural Transient Evoked Otoacoustic
      Emission testing (262 males, 270 females; mean gestational age 39.2 +/- 2.1
      weeks, range 26-43; birth weight: 3,240 +/- 550 g, range 910-4,780). The
      population examined comprised 448 control infants and 84 high-risk for hearing
      loss infants (Joint Committee on Infant Hearing 1994 criteria). All Transient
      Evoked Otoacoustic Emission recordings were performed at comparable
      postconceptional ages. Audiological screening by Transient Evoked Otoacoustic
      Emission recording showed an overall 100% sensitivity, 99.02% specificity, with
      negative and positive predictive values of 100% and 62.5%, respectively. As
      compared to controls, high-risk infants showed: 1. increased rates of Fail-1
      (Transient Evoked Otoacoustic Emissions absent at first examination, 21.4% vs
      9.8%, p = 0.004), Fail-2 (Transient Evoked Otoacoustic Emissions absent on
      retesting: 8.64% vs 1.37%, p = 0.0014), false positives (Transient Evoked
      Otoacoustic Emissions absent/V wave present: 3.7% vs 0.46%, p = 0.029) and true
      positives (Transient Evoked Otoacoustic Emissions absent, V wave absent: 2.47% or
      24.5 per 1,000 live births vs 0.22% or 2.2 per 1,000 live births, p = 0.013); 2.
      significantly reduced Transient Evoked Otoacoustic Emission intensity in the 0.7
      1 kHz (right side) and 1-2 kHz (left side) frequency ranges. Multivariate
      logistic regression analysis showed a significant positive correlation between
      congenital hearing loss and the following risk factors: assisted ventilation
      lasting > 10 days (Odds ratio 14.8; 95% confidence interval, 4.5-48.8, p <
      0.000001), severe birth asphyxia (Odds ratio 5.8; 95% confidence interval; 2.1
      16.1; p = 0.0006) and administration of ototoxic drugs (Odds ratio 4.5; 95%
      confidence interval; 1.4-13.9; p = 0.009). Results of this study confirm the
      feasibility and accuracy of universal neonatal hearing screening based on
      recording Transient Evoked Otoacoustic Emissions. These data stress the
      importance of the risk factors for hearing loss, including prolonged assisted
      ventilation, ototoxic drugs, and severe birth asphyxia.

PMID- 12812131
TI  - Use of titanium mesh in comminuted fractures of frontal sinus anterior wall.
AB  - The personal experience with the surgical treatment of reduction and fixation of
      comminuted fractures of the anterior wall of the frontal sinus is reported.
      Cosmetic results were examined with regard to patients' degree of satisfaction on
      a 0 to 2 scale and nasal function assessed via rhinoscopy and nasal endoscopy
      during clinical follow-up, in the course of which the integrity and functionality
      of the supraorbitary and facial nerves were evaluated. All patients were
      satisfied, on the whole, with the aesthetic result, with 0-degree satisfaction
      (no deformity compared with their condition prior to the injury). The operations
      were performed between the 2nd and 7th post-injury day. The importance of the
      preoperative clinico-radiological work-up is stressed, with particular regard to
      the detection of simultaneous involvement of the inferior and/or posterior wall,
      and to the choice of surgical approach. The evolution of the surgical techniques
      in the treatment of frontal sinus fractures is discussed. With reference to the
      new means of fixation, in cases of comminuted fractures of the anterior wall,
      titanium mesh is preferred. In the Authors' opinion it combines excellent
      fixation with easy adaptability (cosmetic results are good) without requiring in
      the majority of cases, autologous bone grafts.

PMID- 12812132
TI  - Nasal polyposis: microsurgical ethmoidectomy and interruption of autonomic
      innervation vs conventional surgery.
AB  - Nasal polyposis is an invalidating disease which develops through chronic
      inflammation which leads to tissue oedema and eventually polyps. Treatment is
      aimed at eliminating polyps, resolving rhinitis symptoms, re-establishing nasal
      breathing and olfaction and preventing recurrence. The pathogenesis can be
      explained, in part, by degranulation of mast cells and release of mediators
      attracting eosinophils which, in turn, can cause tissue damage and oedema.
      Neurovascular reflexes and factors related to the complex anatomy of ethmoidal
      labyrinth may be responsible for the onset and persistence of oedema. This would
      offer a rationale to treatments modifying ethmoid anatomy and blocking
      neurovascular reflexes in the management of nasal polyposis. The advent of
      microsurgery and of diagnostic and operative endoscopy has led, over the last
      twenty years, to earlier detection and to less traumatic and more precise
      surgical treatment of nasal polyps. With these techniques resection of
      parasympathetic innervation is also possible, which is in keeping with the
      proposed rationale and cannot be easily achieved by conventional surgery. To
      evaluate the impact of this resection on the management of nasal polyposis a
      review of data has been made in a series of patients with diagnosis of nasal
      polyposis established by clinical examination, resistant to pharmacological
      therapy and treated between 1983 and 1998 at the Oto-Neuro-Ophthalmology
      Department of Florence University (Italy). Patients were treated by conventional
      surgery (386 cases), by microsurgery without resection of the parasympathetic
      component of the vidian nerve (97 cases), or by microsurgery with resection of
      this latter component (94 cases). The rate of recurrence and of major post
      operative complications, respectively, were: 39.9% and 4.4% for patients treated
      by conventional surgery; 37.1% and 6.2% with microsurgery without resection of
      parasympathetic innervation; and 25.5% and 2.1% with resection of this
      innervation. The difference in recurrence rate between the three groups was
      significant (p < 0.05). The average disease-free interval was 45.7 months with
      conventional surgery and 53.5 months with microsurgery (regardless of resection
      of innervation). Results show that microsurgery for nasal polyposis together with
      resection of parasympathetic innervation improves results compared to those with
      conventional surgery and does not cause an increase in post-operative
      complications.

PMID- 12812133
TI  - Contact laser surgery in treatment of vocal fold paralysis.
AB  - Vocal fold paralysis is a pathological condition characterised by varying degrees
      of respiratory distress in relation to the degree of glottic stenosis. Dyspnoea
      may be present even when resting and may even require emergency tracheotomy.
      Frequently, the patient arrives for attention after the onset of exertional
      dyspnoea associated with a certain degree of dysphonia. The causes may be central
      or peripheral, more commonly iatrogenic following thyroid or tracheal surgery or
      secondary to injury. The aim of all surgical techniques used in the treatment of
      vocal fold paralysis is to restore a lumen sufficient to guarantee adequate
      breathing through the natural airway, without the patient having to permanently
      maintain the tracheotomy tube, while preserving acceptable phonatory quality.
      Between 1990 and 2001, at the Padua Hospital Unit of Endoscopic Airway Surgery,
      48 patients (27 female, 21 male) were treated for respiratory distress secondary
      to vocal fold paralysis. At the beginning of this experience, 7 patients
      underwent arytenoidectomy with the Ossoff technique. In 34 cases, a modified
      Dennis-Kashima posterior cordectomy was performed. In 7 patients, since widening
      of the airway was necessary, cordectomy was extended to the false homolateral
      chord in 5 cases and to the arytenoid vocal process in another 2. In 9 patients,
      the operation was carried out with a Nd Yag (1064 nm) contact laser; the
      remaining 39 were treated with a GaArAl (810 nm) diode laser in use since 1995.
      Satisfactory results were obtained in all patients first treated by us and not
      already tracheotomised (35). In 23 cases (66%), results were considered "good"
      since no exertional dyspnoea occurred. In 12 patients (34%), the result was
      considered "sufficient" since there was no resting dyspnoea and normal everyday
      activity could be undertaken. Of the 13 patients already tracheotomised on
      arrival, 11 (85%) were decanulated on average 2 months after surgery. In
      conclusion, the present results show that endoscopic posterior cordectomy,
      performed by contact diode laser, gives reliable results, is rapid and simpler to
      perform than arytenoidectomy and guarantees a sufficient airway without impairing
      swallowing, while maintaining entirely acceptable voice quality.

PMID- 12812134
TI  - Pharyngolaryngeal reflux in outpatient clinical practice: personal experience.
AB  - Proximal pharyngolaryngeal reflux now appears to be strictly related to symptoms
      and clinical patterns frequently encountered in clinical ORL practice and which
      are, more often than not, differentiated from classical gastro-oesophageal reflux
      disease. The aim of the study was to evaluate the incidence of the symptoms and
      clinical signs of gastro-oesophageal reflux disease, together with the
      symptomatologic response to a cycle of acid suppression treatment with proton
      pump inhibitors in a non-selected population comprising consecutive patients
      coming to the outpatient unit of the Laryngology Clinic of Universita Cattolica
      of Rome between June and December 2001, all of whom had been examined by the same
      practitioner. Of the 1300 patients evaluated, 52 presented a clinical history and
      chronic pharyngolaryngeal symptoms strongly indicative of gastro-oesophageal
      reflux disease. All selected patients were prescribed a two-month regimen of acid
      suppression therapy (20 mg Omeprazole twice daily, sufficient to confirm the
      clinical suspicion of pharyngolaryngeal reflux ex adiuvantibus (Omeprazole test),
      at the same time obtaining a satisfactory response in the symptomatology, as laid
      out in the guidelines emerging from the 1997 Consensus Conference Report on
      pharyngolaryngeal reflux. The same patients were later interviewed by telephone
      to evaluate the effectiveness of treatment, exclusively in terms of improvement
      in the symptoms. Analysis of the data from the 33 who answered the telephone
      questionnaire revealed a complete symptomatological response in 24 (72.7%),
      partial response in 4 (12.1%) and no response in 5. The Authors stress that,
      despite the known limits of this treatment, linked to proton pump inhibitors
      resistance, the "Omeprazole test", on account of excellent tolerability, lack of
      adverse effects and, above all, non-invasive nature, is feasible in the
      preliminary evaluation to confirm clinical suspicion of gastro-oesophageal reflux
      disease in outpatients, especially when a large-scale pH-metric multielectrode
      investigation is not possible. Furthermore, despite the many epidemiological,
      aetiopathogenetic, clinico-diagnostic and therapeutic aspects which remain to be
      clarified, there is no doubt that gastro-oesophageal reflux disease on account of
      the particular clinical features, directly involves the ORL specialist not only
      in the diagnostic, but also in the therapeutic phase.

PMID- 12812135
TI  - Atypical carcinoid tumour of the larynx treated with CO2 laser excision: case
      report.
AB  - A case of atypical laryngeal carcinoid tumour of the right aryepiglottic fold is
      described in a 56-year-old female. The patient presented a 4-year history of
      dysphagia, occasional dyspnoea and pain originating in the right tonsillar fossa
      and radiating to the ear. A sessile, submucosal neoplasm of about 1 cm in
      diameter and apparently benign appearance was detected endoscopically in the
      supraglottic region. An excisional biopsy was collected by CO2 laser during
      direct microlaryngoscopy from which a diagnosis of atypical carcinoid tumour of
      the larynx was made, and later confirmed by histochemical and immunohistochemical
      staining. Post-operative course was uneventful, with return to a normal diet per
      os on the first post-operative day. Histopathological evaluation of the excised
      specimen revealed the presence of a neoplasm in proximity of the surgical
      margins, which were not, however, directly involved by the tumour. The close
      endoscopic follow-up was, nonetheless, implemented in order to promptly detect
      any evidence of relapse of the disease. After 18 months, a lesion, suspected of
      being a recurrence, was found, in the site of the original tumour. CO2 laser
      excision was again carried out, this time allowing for wider margins on the
      surgical resection. The post-operative diagnosis confirmed the clinical
      hypothesis of recurrence of atypical carcinoid tumour. The patient is presently
      alive and free from disease 7 years after the second endoscopic procedure. The
      difficult aspects of clinical and histopathological diagnoses, the surgical
      treatment as well as endoscopic and instrumental follow-up of this rare condition
      are discussed.

PMID- 12812136
TI  - Epidemiological studies of rotavirus infection in Guinea-Bissau, West Africa.

PMID- 12812137
TI  - Molecular control of the cell cycle in cancer: biological and clinical aspects.
AB  - The RB1 pathway and the p53 pathway represent important, interconnected
      biochemical units frequently perturbed in human cancer. Essential tumor
      protective mechanisms, such as cellular growth control and apoptosis, are
      regulated through these systems. Comprehensive studies of these pathways,
      including most known pathway components, have not been performed in NHL. We
      therefore analyzed the involvement of aberrations of these pathways in NHLs from
      the population-based West-Danish NHL registry, LYFO registry, as well as in a
      series of neurofibromatosis 1-related tumors. The aim of the studies was to
      obtain information about extent and interrelation of alterations of pathway
      components, as well as clinical information such alterations might provide. We
      found that alteration of components of one or both of these pathways are very
      common, occurring in the vast majority of DLCLs. Our data suggest that the
      pathways are not entirely linear in lymphomagenesis. The p53 pathway components
      MDM2 and p53 were frequently altered in the same lymphoma indicating that the
      role of MDM2 in lymphomagenesis is not entirely dependent on the downstream
      target, p53. The linearity of the RB1 pathway was clearer as only 1 of 34 DLCLs
      showed aberration of more than one of the components cyclin D3, p16INK4A, and
      pRB. An intriguing novel observation was that p16INK4A inactivation was
      associated with increased expression of cdk4, a kinase target of p16INK4A
      inhibitory function. This could indicate the existence of a regulatory feedback
      loop between p16INK4A and cdk4. Cyclin D3 has yet to be established as an
      oncoprotein. Our finding of cyclin D3 overexpression in a significant number of
      DLCLs (including all thyroid lymphomas analyzed), as well as the intimate inverse
      relation to other RB1 pathway alterations suggest, that cyclin D3 is important in
      lymphomagenesis. However, further studies are needed to implicate cyclin D3
      definitively as an oncoprotein. Our data contain several lines of evidence
      supporting roles of CDKN2A and MDM2 in progression of neoplastic disease. We
      found that loss of p16INK4A coincided with transformation of neurofibromas to
      malignant peripheral nerve sheath tumors in neurofibromatosis 1 patients.
      Furthermore, one DLCL lost CDKN2A from diagnosis to relapse. MDM2 overexpression
      was more frequent in aggressive than in indolent lymphomas, and in follicle
      center lymphomas none of our follicle center grade I/II lymphomas overexpressed
      MDM2. In contrast, MDM2 was overexpressed in 60% of grade III/diffuse follicle
      center lymphomas. Clinical correlations revealed novel and interesting findings.
      Both p53 disruption and low expression of E2F-1 correlated with poor response of
      aggressive lymphomas to treatment. Chemotherapeutic regimens used in lymphoma
      treatment are based on apoptosis induction, and as both E2F-1 and p53 are
      regulators of apoptosis, it is possible that the observed treatment failure is
      associated with reduced E2F-1- and p53-mediated apoptosis. Survival analyses
      revealed numerous novel and potentially important findings. Several of the
      studied cell cycle regulators carried independent prognostic value in various
      subsets of lymphomas. In DLCL, both p16INK4A inactivation and reduced E2F-1
      expression conferred shortened survival. p53 alteration was associated with poor
      prognosis of both B-cell and, especially, T-cell lymphoma. Low expression of p27,
      a cell cycle regulator haplo-insufficient for tumor suppression, predicted poor
      outcome in indolent and aggressive lymphoma, and overexpression of cyclin D3 was
      associated with poor prognosis in indolent lymphomas. Finally, MDM2
      overexpression identified among patients with follicle center lymphomas,
      extranodal marginal zone lymphomas, and mantle cell lymphomas cases with poor
      prognosis. While these results must necessarily be confirmed on larger
      prospective series of patients, the data nonetheless suggest that valuable
      prognostic information can be provided by studies of these cell cycle regulators.

PMID- 12812138
TI  - Alcohol abuse and postoperative morbidity.
AB  - Patients who drink too much have more complications after surgery. The aim of
      this thesis was to evaluate the evidence, possible mechanisms, and prevention of
      the increased postoperative morbidity in alcohol abusers, defined by a
      consumption of at least five drinks per day. The literature could be criticised
      for several methodological flaws. Nevertheless, the results are in agreement
      showing moderate to strong evidence of increased postoperative morbidity after
      surgical procedures on alcohol abusers. There is weak to moderate evidence of
      increased postoperative mortality, hospital stay, and re-operation. The personal
      and economic consequences are tremendous. The incidence of alcohol abusers
      undergoing surgery was 7% to 49%, according to gender and diagnosis. They have
      been identified by a self-reported alcohol intake, which implies the possibility
      of underestimation. Alcohol markers could be used for a more precise
      identification of alcohol abuse. However, the inability of the questionnaires to
      detect short-term changes in intake and abuse without dependence, the
      inconsistent predictive values of the biological markers, and the lack of
      evidence of an association to postoperative morbidity reduces their usefulness. A
      detailed alcohol history is therefore recommended. The pathophysiology may
      include alcohol-induced organ dysfunctions. We demonstrated that subclinical
      cardiac insufficiency, immune incompetence, and haemostatic imbalance were
      already present preoperatively. A relation between the various lesions remains to
      be investigated. The surgical stress response was greater in alcohol abusers,
      which may further compromise the already dysfunctioning organs, thus leading to
      the documented increase in postoperative morbidity. Withdrawal from alcohol
      reverses organic dysfunction in non-surgical patients. Haemostasis normalises
      after one to four weeks, cardiac function after one month, immune function after
      two months, and response to external stress after three months. Accordingly, our
      small randomised investigation has shown that one month of abstinence before
      surgery improves several organic dysfunctions and reduces postoperative
      morbidity. We have demonstrated that prevention before surgery is possible. The
      study has methodological flaws, so further studies are required before final
      recommendations can be given. However, in the meantime clinical guidelines for
      alcohol abusers undergoing surgery should include up-to-date patient information
      and four weeks of abstinence before surgery, in accordance with the evidence
      based association, the potential prevention attained by preoperative abstinence,
      and the best clinical practice. Implementation should be monitored in the
      clinical databases. In future, all patients admitted to surgery should be offered
      a health promoting dialogue with the surgeon, anaesthesiologist, general
      practitioner, or other health professionals, which focuses on alcohol among other
      risk factors in relation to the operative treatment, diagnosis and prognosis. A
      beneficial effect attainable from this multi-modal prevention and fast track
      surgery should be investigated among the alcohol abusers.

PMID- 12812139
TI  - Clinical and experimental studies on inflammatory mediators during AIDS
      associated Pneumocystis carinii pneumonia.
AB  - This thesis is based on studies carried out during my appointment as a research
      fellow at the Department of Infectious Diseases, Hvidovre Hospital, University of
      Copenhagen, Denmark from 1993 to 1997. Part of this period was spent as a guest
      researcher at the Critical Care Medicine Department, National Institutes of
      Health, Bethesda, Maryland, USA. Pneumocystis carinii pneumonia (PCP) is the most
      frequent AIDS defining illness over the past 20 years. PCP is associated with
      considerable morbidity and mortality. An inflammatory reaction to P. carinii is
      believed to cause respiratory failure. This thesis has attempted to delineate
      important mechanisms of the inflammatory cascade, and to determine how
      inflammation is initiated during PCP. In histopathological studies of lung
      specimens it was shown that PCP caused significant inflammation and destruction
      of tissue. Specific pathological changes of the alveolar epithelium was observed
      in PCP but not for other HIV related lung diseases. By determining concentrations
      of soluble markers of immune activation we found that anti-microbial therapy
      exacerbated an ongoing inflammatory reaction. Adjuvant glucocorticosteroids
      suppressed levels of soluble immune markers. Bronchoalveolar lavage (BAL)
      neutrophilia has been associated with disease severity, and an increased risk of
      death from PCP. Through competitive inhibitory studies, we showed that BAL fluid
      neutrophil chemotactic activity largely was explained by the presence of
      interleukin-8 (IL-8). Further, we showed a correlation between high levels of BAL
      fluid IL-8 and mortality. Adjuvant treatment with glucocorticosteroids lowered
      BAL fluid IL-8 levels. In experimental studies we found that P. carinii Major
      Surface Antigen (MSG) induced IL-8 and tumor necrosis factor-alpha secretion from
      human monocytes and an alveolar epithelial cell line (A549). Binding of MSG to
      monocytes appeared to be mediated by mannose receptors, while A549 cells
      recognized MSG through mannose and glucan receptors. Glucocorticosteroids
      attenuated IL-8 secretion from A549 cells. These studies have confirmed that P.
      carinii infection induces tissue damage through a significant inflammatory
      response initiated by secretion of inflammatory mediators. Glucocorticosteroids
      attenuates the inflammatory response.

PMID- 12812140
TI  - The Danish National Cohort Study (DANCOS).
AB  - This article gives an overview of  a nationally representive public health
      research database in Denmark, the Danish National Cohort Study (DANCOS).  DANCOS
      combines baseline data from health interview surveys with both pre- and post
      baseline data from national health registries with date from a re-interview
      survey.  As part of the national health interview survey programme, three nation
      wide surveys were conducted in 1986/1987, 1991 and 1994.  The samples in the
      three cohorts consisted of 23,096 adult Danes ages 16 years and older, and 18,296
      (79.2%) were personally interviewed on socio-economic status; living conditions;
      health behaviour; self-rated health; morbidity; utilization of health services;
      and the consequences of illness and  disability.  Each Dane is equipped with a
      unique identification number that allows highly accurate linkage of data in the
      health surveys and in the national health and administrative registries.  All
      respondents and non-respondents were followed through 2002, a total of 3,796 had
      died and 249 had emigrated.  The specific cause of death for 2,485 people was
      recorded in the Danish Register of Causes of Death, updated through 1998.  For
      1978-1977, the Danish National Hospital Register contained information about
      16,503 persons who had been hospitalized for any illness or related health
      problems, accounting for 70,925 hospital admissions.  For 1970-1997, the Danish
      Psychiatric Central Register comprised information on 1691 persons.  For 1990
      1997,  the Danish National Health Service Register recorded 980,043 contacts with
      general practitioners and specialist physicians.  For 1943-1996, the Danish
      cancer Registry contained information about one or more cancer diseases among
      1,432 people.  A total of 4,334 people in the 1994 cohort were re-interview in
      2000.  DANCOS allows for a wide range of analysis in a historical prospective
      design of determinants of morbidity and mortality, of health care utilization and
      of the social effects of ill health.  DANCOS also allows studies of
      methodological issues, including analyzing the characteristics of non
      respondents.

PMID- 12812141
TI  - Is low back pain in youth associated with weight at birth? A cohort study of 8000
      Danish adolescents.
AB  - INTRODUCTION: Low back pain has been associated with an increased risk of several
      diseases and with poor general health. Also low birth weight has been associated
      with an increased susceptibility to various diseases as well as with poor general
      health. Thus, low birth weight could be a common factor--indicating a general
      frailty with an increased risk of both low back pain and overall morbidity. To
      our knowledge, the association between low back pain and birth weight has not
      previously been investigated. This study investigates the correlation between
      birth characteristics and low back pain in adolescence. MATERIAL AND METHODS:
      Analyses are based on data from The Danish Twin Registry. Information about low
      back pain is from a postal survey, and information about birth characteristics
      are from The Danish Medical Birth Register. Analyses include 8278 individuals
      aged 12-22 years--an age at which they are still largely unaffected by the
      influence of working life. Possible associations between low back pain, birth
      weight, birth length, ponderal index, gestational age and Apgar scores are
      investigated by the use of logistic regression analysis. RESULTS: The odds ratio
      for the lifetime prevalence of low back pain increases from 1.21 (0.94-1.56) for
      a birth weight of 2000-2500 g to 1.97 (1.35-2.88) for a birth weight of > 3500 g
      compared to the smallest weight group (< 2000 g) in males, whereas there is a
      small statistically insignificant, positive association for females. The same
      pattern is seen for the one-year prevalence of low back pain. No associations are
      documented between low back pain and other birth factors. The positive
      association between low back pain and birth weight is independent of other birth
      factors and of anthropometric measures in adolescence. CONCLUSION: There is a
      statistically significant association between high birth weight and the risk of
      developing low back pain in males but not in females. Our results do not indicate
      that frailty at birth increases the risk of low back pain in adolescence.

PMID- 12812142
TI  - Negative association between smoking and anti-saccharomyces cerevisiae antibodies
      in Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is a polygenic multifactorial heterogeneous
      disease. Anti-Saccharomyces Cerevisiae antibodies (ASCA) correlate highly with CD
      and are present in 50-80% of patients. The reason for ASCA positivity or
      negativity in CD is unknown. The aim of our work was to analyse clinical,
      epidemiological and genetic characteristics in ASCA+ or ASCA- CD patients.
      METHODS: 113 patients with CD were tested for ASCA (IgA and IgG) by using a
      commercial kit (Medipan Diagnostica). Age, gender, systemic manifestations,
      familial form of disease, age at diagnosis, location and behaviour of the
      disease, smoking habit as well as genotyping for -308 TNF gene polymorphisms were
      determined. RESULTS: 38.9% CD patients were negative for both IgA and IgG ASCA
      while 61.1% were ASCA positive (respectively IgA and IgG: 31.9%; IgA only: 9.7%;
      IgG only: 19.5%). The only significant difference between ASCA+ and ASCA-
      patients was for smoking habit: there were 29% smokers in ASCA+ versus 50% in
      ASCA- CD patients (P = 0.03). This low proportion of smokers was more prominent
      in ASCA IgA+ patients than in isolated ASCA IgG+ patients (25.6% versus 45.5%)
      and was minimal in patients with high titers of ASCA IgA (0/8). Logistic
      regression showed smoking habit still borderline for significance (P = 0.057).
      CONCLUSIONS: Our results suggest a negative association between smoking and ASCA
      positivity in CD. This association was more prominent for ASCA IgA+. It indicates
      that smoking habit should be taken into account when analysing ASCA status in CD
      patients and may suggest an influence of smoking on immunization against
      intestinal material.

PMID- 12812143
TI  - Modulation of liver injury by interleukin-10.
AB  - Inflammation is commonly observed in liver diseases and is frequently complicated
      by fibrosis and cirrhosis in end-stage disease. The only curative treatment for
      cirrhotic patients is liver transplantation. However, organ shortage as well as
      an increasing organ demand call for early treatment of liver disease and
      prevention of fibrosis. Experimental data have shown the critical role of pro
      inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma) in the development of liver injury. Here, we review
      our work on the role of endogenously produced interleukin-10 (IL-10), a potent
      anti-inflammatory cytokine, in several experimental models of acute and chronic
      liver injury. First, in acute macrophage-mediated hepatitis induced by
      galactosamine/lipopolysaccharide administration, IL-10 neutralisation led to a
      more severe liver damage, whereas IL-10 injection, even delayed, was able to
      limit liver necrosis. A similar protective effect of IL-10 was observed in acute
      T cell-mediated hepatitis induced by concanavalin A (Con A) injection. The
      immunoregulatory role of IL-10 was then established after repeated exposition to
      Con A. In carbon tetrachloride liver injury, two other properties of IL-10 have
      been suggested: modulation of hepatocyte proliferation and modulation of liver
      fibrosis. Finally, the potential therapeutic applications in human liver disease
      as well as the potential side effects are discussed.

PMID- 12812144
TI  - Hepatitis C: screening, treatment and prevention practical guidelines.

PMID- 12812145
TI  - Primary prevention of colorectal cancer.

PMID- 12812146
TI  - Traumatic neuroma of the cystic duct with biliary obstruction. Report of a case.
AB  - A case of amputation neuroma of the biliary tract occurring 12 years after a
      cholecystectomy is reported. The patient, a 81 year-old man, presented with
      obstructive jaundice due to a stricture of the extrahepatic biliary tract. The
      stricture was resected and biliary reconstruction was achieved with a Roux-en-Y
      jejunal loop. The diagnosis of neuroma was obtained only at histology that showed
      hyperplastic nerve bundles, positive for protein S 100. The patient is well one
      year and six months after surgery without signs of recurrence of the stricture.
      Although the amputation neuroma of the biliary tract has already been reported,
      it seems worthwhile to emphasise this further report. This lesion is an unusual
      cause of benign stricture of the biliary tract that may pose difficult diagnostic
      problems.

PMID- 12812147
TI  - Prevalence of lupus anticoagulant in multiparous women in Benin City, Nigeria.
AB  - Lupus anticoagulant which in the past was regarded as a laboratory nuisance is
      now known to be associated with numerous clinical conditions including thrombosis
      and recurrent foetal loss, however, no work has been done to assess its
      prevalence in non-pregnant healthy multiparous women. Our aim therefore was to
      determine the prevalence of lupus anticoagulant in non-pregnant multiparous
      Nigerian women of childbearing age. Fifty non-pregnant multiparous women who were
      considered healthy following verbal interviews were studied. An eligibility
      criterion was used. Coagulation studies were performed on plasma samples from all
      the women using the Kaolin clotting time. Mixing experiments were conducted on
      samples with prolonged clotting time to detect the presence of the lupus
      anticoagulant. The Kaolin clotting time ratio of greater than or equal to 1.2 was
      considered positive for the lupus anticoagulant. Forty-four (88%) of the 50 women
      had a normal cloning time, 2(4%) had subnormal clotting time while 4(8%) of them
      had a prolonged Kaolin clotting time. Mixing experiments on these 4 samples
      revealed Kaolin clotting time ratios of over 1.2, signifying the presence of the
      lupus anticoagulant (i.e. 8 per cent prevalence) among the population of women
      studied Multiparous women with the lupus anticoagulant may not be symptomatic
      therefore the anticoagulant should be screened for in women with unexplained
      prolongation of cloning time. We recommend that these women should be followed up
      especially in pregnancy to forestall any of the obstetric complications that have
      been associated with the lupus anticoagulant.

PMID- 12812149
TI  - Liquid chromatography problem solving and troubleshooting. Monolith columns.

PMID- 12812148
TI  - Increasing use of psychotropic medications in children and adolescents: what does
      it mean?

PMID- 12812150
TI  - Proceedings of the annual meeting of the Female Sexual Function Forum. October
      2001, Boston, Massachusetts, USA.

PMID- 12812151
TI  - Nutritional and physiologic significance of human milk proteins.
AB  - Human milk contains a wide variety of proteins that contribute to its unique
      qualities. Many of these proteins are digested and provide a well-balanced source
      of amino acids to rapidly growing infants. Some proteins, such as bile salt
      stimulated lipase, amylase, beta-casein, lactoferrin, haptocorrin, and alpha1
      antitrypsin, assist in the digestion and utilization of micronutrients and
      macronutrients from the milk. Several proteins with antimicrobial activity, such
      as immunoglobulins, kappa-casein, lysozyme, lactoferrin, haptocorrin, alpha
      lactalbumin, and lactoperoxidase, are relatively resistant against proteolysis in
      the gastrointestinal tract and may, in intact or partially digested form,
      contribute to the defense of breastfed infants against pathogenic bacteria and
      viruses. Prebiotic activity, such as the promotion of the growth of beneficial
      bacteria such as Lactobacilli and Bifidobacteria, may also be provided by human
      milk proteins. This type of activity can limit the growth of several pathogens by
      decreasing intestinal pH. Some proteins and peptides have immunomodulatory
      activities (eg, cytokines and lactoferrin), whereas others (eg, insulin-like
      growth factor, epidermal growth factor, and lactoferrin) are likely to be
      involved in the development of the intestinal mucosa and other organs of
      newborns. In combination, breast-milk proteins assist in providing adequate
      nutrition to breastfed infants while simultaneously aiding in the defense against
      infection and facilitating optimal development of important physiologic functions
      in newborns.

PMID- 12812152
TI  - Protein requirements during the first year of life.
AB  - The composition of human milk provides the model for estimated total protein and
      essential amino acid requirements during infancy. However, both the total protein
      content and the concentrations of individual proteins in human milk change
      throughout the first year of lactation. Recent reassessments of estimated
      requirements have resulted in lower total protein recommendations and have
      emphasized the provision of alpha-amino nitrogen because most nonprotein nitrogen
      is not used for maintenance or tissue deposition. In clinical studies, formulas
      containing various whey-to-casein ratios and having total protein concentrations
      in the range of 13-15 g/L were shown to promote adequate growth and to result in
      biochemical measures of protein nutritional status similar to those in breastfed
      infants. In the second half of infancy, human milk can provide most of the
      protein needed, provided a modest protein supply is obtained from weaning foods.
      In special situations in which greater protein intakes are desired, special
      preparations of protein might be needed.

PMID- 12812153
TI  - Advances in nutritional modifications of infant formulas.
AB  - Modifications to infant formulas are continually being made as the components of
      human milk are characterized and as the nutrient needs of diverse groups of
      infants are identified. Formulas with long-chain polyunsaturated fatty acids
      added in amounts similar to those in human milk have recently become available in
      the United States; infants fed these formulas or human milk have higher tissue
      concentrations of long-chain polyunsaturated fatty acids and reportedly have
      better visual acuity than do infants fed nonsupplemented formulas. Selenium, an
      important antioxidant, is present in higher concentrations in human milk than in
      non-fortified cow milk-based formula, and the selenium intakes of infants fed
      nonfortified formulas are reported to be at or below recommended levels. Blood
      selenium concentrations and plasma glutathione peroxidase activity are higher in
      infants fed selenium-supplemented formulas or human milk than in infants fed non
      fortified formulas. Nucleotides and their related products play key roles in many
      biological processes. Although nucleotides can be synthesized endogenously, they
      are considered "conditionally essential." Nucleotide concentrations in human milk
      are higher than in unsupplemented cow milk-based formulas, and studies in animals
      and human infants suggest that dietary nucleotides play a role in the development
      of the gastrointestinal and immune systems. Formulas for preterm infants after
      hospital discharge are designed to meet the needs of a population in whom growth
      failure is common. Several studies have shown that preterm infants fed nutrient
      enriched formulas after hospital discharge have higher rates of catch-up growth
      than do infants fed standard term-infant formulas.

PMID- 12812154
TI  - Infant formulas with increased concentrations of alpha-lactalbumin.
AB  - Human and bovine milk differ substantially in the ratio of whey to casein protein
      (approximately 60:40 in human milk and approximately 20:80 in bovine milk) and in
      the proportions of specific proteins. Although current infant formulas closely
      mimic the ratio of total whey to casein inhuman milk, the concentration of a
      lactalbumin (the dominant protein in human milk) is relatively low in formula,
      whereas beta-lactoglobulin, a protein not found in human milk, is the most
      dominant whey protein in formula. Because of the differences in the protein
      profiles of human milk and infant formula, amino acid profiles also differ. To
      meet all essential amino acid requirements of infants, formula concentrations of
      protein must be higher than those in human milk. Recently, whey sources with
      elevated concentrations of alpha-lactalbumin have become available, which
      permitted the development of formulas with increased concentrations of this
      protein and decreased concentrations of beta-lactoglobulin. alpha-Lactalbumin is
      rich in tryptophan, which is typically the limiting amino acid in formula, and as
      a result, formulas have been developed with lower protein but higher tryptophan
      concentrations. This type of formula may offer a number of advantages to the
      neonate, which include producing plasma tryptophan concentrations equal to those
      found in breastfed infants and obviating the need for the body to dispose of
      excess nitrogen loads.

PMID- 12812155
TI  - Applications and computational strategies for the two-point mixture index of fit.
AB  - Although numerous descriptive measures have been proposed for assessing model fit
      when analysing frequency tables, the two-point mixture index of fit proposed by
      Rudas, Clogg, and Lindsay possesses features that make this index especially
      appealing in many applied research settings. In particular, the index has an
      intuitive interpretation that does not depend upon the specific nature of the
      model being assessed and is not sensitive to sample size. Also, the index can be
      applied when models are fitted to virtually any frequency table. This paper
      summarizes the underlying theory and addresses issues of estimation for goodness
      of-fit tests for one-way or multi-way frequency tables as well as for certain
      latent variable models. In addition, a new approach for estimating a lower
      confidence bound for the index is presented.

PMID- 12812156
TI  - 'Suicide tourists' go to the Swiss for help in dying.

PMID- 12812157
TI  - Bad seed or bad science?

PMID- 12812158
TI  - State can make inmate sane enough to execute.

PMID- 12812159
TI  - An ethical dilemma with few precedents.

PMID- 12812160
TI  - Forcing psychiatric drugs on defendants is weighed.

PMID- 12812161
TI  - Doctor explains why he blew the whistle.

PMID- 12812162
TI  - Broad movement is backing embryo stem cell research.

PMID- 12812163
TI  - Buying time: doctors debate the ethics of care and cost.

PMID- 12812164
TI  - Clinics hold more embryos than had been thought.

PMID- 12812165
TI  - Inquiry shows British scientists took brains without families' consent.

PMID- 12812167
TI  - Gov. Jeb Bush to seek guardian for fetus of rape victim.

PMID- 12812168
TI  - 400,000 embryos and counting.

PMID- 12812169
TI  - Ruling supports parents' rights to decide on child's life support.

PMID- 12812170
TI  - 2 paths of Bayer drug in 80's: riskier one steered overseas.

PMID- 12812171
TI  - Aetna agreement with doctors envisions altered managed care.

PMID- 12812172
TI  - DNA of blacks to be gathered to fight illness.

PMID- 12812173
TI  - If biology is destiny, when shouldn't it be?

PMID- 12812174
TI  - Seeing risk and reward through a patient's eyes.

PMID- 12812175
TI  - Bibliography. Current world literature. Surgery.

PMID- 12812177
TI  - Bibliography. Current world literature. Emergency and critical care pediatrics.

PMID- 12812176
TI  - Court papers suggest scale of drug's use: lawsuit says doctors were paid
      endorsers.

PMID- 12812178
TI  - Clear thinking on cloning.

PMID- 12812179
TI  - Deploying soldiers put family plans on ice.

PMID- 12812180
TI  - The front lines of biowarfare: today's anti-terrorism effort casts early test
      subjects in new light.

PMID- 12812181
TI  - Co-operation despite disagreement: from politics to healthcare.
AB  - Political interaction among citizens who hold opposing moral views commonly
      requires reaching beyond toleration, toward actual co-operation with policies one
      opposes. On the more personal level, however, regarding (e.g.) interactions
      between healthcare providers and patients, several authors emphasize the
      importance of preserving integrity. But those who oppose any 'complicity in evil'
      often wrongly conflate instances in which the other's position is (and should be)
      totally rejected with instances of legitimate, although deep, disagreement.
      Starting with a striking example from the context of a particular tradition, I
      argue generally that in the latter sort of disagreements, talk of 'complicity'
      should be largely replaced with a more co-operative moral stance, grounded in a
      pluralistic framework. Co-operation Despite Disagreement (CDD) should be sought
      either for institutional reasons--akin to the political--or for relational
      reasons. CDD involves sharing another's perspective and sometimes calls for
      adopting another's moral judgements in preference to one's own. I seek to
      identify some of the conditions and circumstances that would justify such a
      shift, particularly in scenarios involving assistance, such as physician-assisted
      suicide (PAS) or the role of an anaesthesiologist in abortion. This discussion is
      meant to provide examples of the kind of second-order reasons appropriate for
      determining the terms for CDD-- in distinction from first-order considerations
      (e.g., the much-contested 'active/passive' distinction) which are likely to be
      the subject of the initial disagreement and hence cannot serve to resolve it.

PMID- 12812182
TI  - 'Hitting you over the head': oncologists' disclosure of prognosis to advanced
      cancer patients.
AB  - The disclosure of prognosis to terminally ill patients has emerged as a recent
      concern given greater demands for patient involvement in medical decision-making
      in the United States. As part of the informed consent process, American
      physicians are legally and ethically obligated to provide information to such
      patients about risks, benefits, and alternatives of all available treatment
      options including the use of experimental therapies. Although not legally
      required, the disclosure of terminal prognosis is ethically justified because it
      upholds the principle of self-determination and enables patients to make
      treatment decisions consistent with their life goals. To understand oncologists'
      attitudes about disclosing prognostic information to cancer patients with
      advanced disease, we interviewed fourteen oncologists and conducted one focus
      group of medical fellows. Although oncologists reported to disclose prognosis in
      terms of cancer not being curable, they tend to avoid using percentages to convey
      prognosis. Oncologists' reported reluctance to disclosing prognosis was conveyed
      through the use of metaphors depicting the perceived violent impact of such
      information on patients. Oncologists' reluctance to disclose prognosis and
      preserve patient hope are held in check by their need to ensure that patients
      have 'realistic expectations' about therapy. We discuss these data in light of
      the cultural, ethical, and legal dimensions of prognosis disclosure, patient hope
      and the doctor-patient relationship, and recommend ways to enhance the
      communication process.

PMID- 12812183
TI  - The exploitation argument against commercial surrogacy.
AB  - This paper discusses the exploitation argument against commercial surrogacy: the
      claim that commercial surrogacy is morally objectionable because it is
      exploitative. The following questions are addressed. First, what exactly does the
      exploitation argument amount to? Second, is commercial surrogacy in fact
      exploitative? Third, if it were exploitative, would this provide a sufficient
      reason to prohibit (or otherwise legislatively discourage) it? The focus
      throughout is on the exploitation of paid surrogates, although it is noted that
      other parties (e.g. 'commissioning parents') may also be the victims of
      exploitation. It is argued that there are good reasons for believing that
      commercial surrogacy is often exploitative. However, even if we accept this, the
      exploitation argument for prohibiting (or otherwise legislatively discouraging)
      commercial surrogacy remains quite weak. One reason for this is that prohibition
      may well 'backfire' and lead to potential surrogates having to do other things
      that are more exploitative and/or more harmful than paid surrogacy. It is
      concluded therefore that those who oppose exploitation should (rather than
      attempting to stop particular practices like commercial surrogacy) concentrate
      on: (a) improving the conditions under which paid surrogates 'work'; and (b)
      changing the background conditions (in particular, the unequal distribution of
      power and wealth) which generate exploitative relationships.

PMID- 12812184
TI  - [Proceedings of the Polish Scientific Conference on Occupational Medicine. June 5
      8, 2002, Kielce, Poland].

PMID- 12812185
TI  - Update on unethical use of placebos in randomised trials.
AB  - The most recent (Fifth) revision of the Declaration of Helsinki, adopted in
      October 2000 by the World Medical Association (WMA), reinforces the longstanding
      prohibition against offering placebo instead of effective therapy. The WMA left
      no doubt that if a beneficial treatment for a condition has already been
      recognised, it is unethical to offer placebo in place of such treatment to anyone
      in a study of the same condition. We have previously drawn attention to the
      discrepancy between the spirit of the Declaration and the common practice of
      using placebo controls in randomised trials even if effective treatment exists.
      Despite the mandates of the Declaration of Helsinki and concern from ethicists
      and scientists, the US Food and Drug Administration (FDA) continues to demand and
      defend placebo-controlled evidence of efficacy and safety for the development of
      many new pharmaceuticals, even if effective therapy exists. We suggest that the
      FDA's arguments defending their practice are insufficient to justify medical
      research that violates the Declaration of Helsinki.

PMID- 12812186
TI  - [Pediatric Oncology Conference in observance of the 25th anniversary of the
      Polish Pediatric Leukemia and Lymphoma Study Group. May 26-28, 1999. Gdansk,
      Poland].

PMID- 12812187
TI  - An increased rate of seropositivity for immunoglobulin G antibodies to Chlamydia
      pneumoniae.

PMID- 12812188
TI  - Darkness and myopia progression.

PMID- 12812189
TI  - Proceedings of the 50th Montagna Annual Symposium on the Biology of Skin.
      Snowmass, Colorado, July 27-31, 2001.

PMID- 12812190
TI  - Darkness and myopia progression.

PMID- 12812191
TI  - Access and use of health care vary by type of Medicaid managed care program.

PMID- 12812192
TI  - Time-Resolved Chemistry: From Structure to Function. University of Manchester,
      United Kingdom, 24-26 June 2002.

PMID- 12812193
TI  - Mechanism of diarrhea in collagenous colitis.

PMID- 12812194
TI  - The role of polymorphism in manganese superoxide dismutase in susceptibility to
      alcoholic liver disease.

PMID- 12812195
TI  - Supine-prone SPECT myocardial perfusion imaging: the poor man's attenuation
      compensation.

PMID- 12812196
TI  - Discussion on predictors of response to infliximab in patients with Crohn's
      disease.

PMID- 12812197
TI  - Proceedings of the symposium on Tissue engineering of cartilage and bone. London,
      United Kingdom, 9-11 April 2002.

PMID- 12812198
TI  - Weight-based ribavirin with pegylated interferon alfa 2b: benefits, risks, and
      the origin of the evidence.

PMID- 12812199
TI  - Optimal use of propranolol.

PMID- 12812200
TI  - Discussion on the biologic therapy of inflammatory bowel disease.

PMID- 12812201
TI  - Biological comlpexity. Colloquium proceedings. Paris, France, 11-12 June 2002.

PMID- 12812202
TI  - Fruits and vegetables: do they protect from gastric cancer?

PMID- 12812203
TI  - Barrett's esophagus and heater probe.

PMID- 12812204
TI  - Lethal injection, autonomy and the proper ends of medicine.
AB  - Gerald Dworkin has argued that it is inconsistent with the proper ends of
      medicine for a physician to participate in an execution by lethal injection. He
      does this by proposing a principle by which we are to judge whether an action is
      consistent with the proper ends of medicine. I argue: (a) that this principle, if
      valid, does not show that it is inconsistent with the proper ends of medicine for
      a physician to participate in an execution by lethal injection; and (b) that this
      principle is not valid, and this is because it mistakenly views the promotion of
      patient autonomy as one of the proper ends of medicine. Rather, I propose, we
      should view respect for a patient's autonomy as a constraint on the pursuit of
      the proper ends of medicine, rather than as one of the proper ends itself. With
      this revised understanding of the proper ends of medicine, we can conclude that
      it is inconsistent with the proper ends of medicine for a physician to
      participate in an execution by lethal injection.

PMID- 12812205
TI  - [Our instructor, Istvan Weszpremi].
AB  - The eminent Transylvanian historian of medicine, Prof. Samuel Izsak calls our
      attention to the fact that Istvan Weszpremi's biographical work - published in
      the 18th century -- is still an important source and guide for researchers. Based
      on three examples - on those of Ascanius, Adam Molnar and Mihail Halici -, he
      shows that Weszpremi's work even today has proved useful in solving historical
      problems.

PMID- 12812206
TI  - History of eradication of malaria in Croatia.
AB  - Malaria as a disease of miasmatic origin was known of as early as in the Ancient
      times. The first written documents on malaria in Croatia date from the 16th
      century, and concern Istria. Until the end of the 16th century, malaria was
      spread on almost the whole territory of Croatia. The first studies of the disease
      were performed as early as in the 18th century. The first piece of work on
      malaria in Croatia "De morbo Naroniano tractatus" (on the "Neretva disease") was
      written by Paduan professor Giusepe Antonio Pujati (1701-1760). The term
      "malaria" (after the Italian mala-aria, meaning bad air) was first mentioned in
      the gazette "Danica Ilirska" in 1837. During the 19th century, the sanitization
      of malaric areas in Istria and the Neretva valley was carried out with the aim of
      eradication of the disease. However, the first significant results were not
      achieved until the beginning of the 20th century following the arrival of Dr.
      Robert Koch and his associates to the Islands of Brijuni. They managed to
      eradicate malaria by systematic quininisation of the whole population and a
      number of other procedures like land-improvement or population education. Robert
      Koch's method of eradication of malaria showed outstanding results in 1903.
      According to physician Mauro Gioseffi's report from 1932 there haven't been
      significant outbreaks of malaria since those times.

PMID- 12812208
TI  - [Present existing problems and their counter-measures in prevention and treatment
      of glaucoma].

PMID- 12812207
TI  - Lethal injection, autonomy, and the proper ends of medicine: a response to David
      Silver.

PMID- 12812209
TI  - Abstracts of the 48th Annual Meeting of the Health Physics Society. 20-24 July
      2003, San Diego, California, USA.

PMID- 12812211
TI  - Abstracts of the 36th Annual Meeting of the Society for Epidemiologic Research.
      Atlanta, Georgia, USA. June 11-14, 2003.

PMID- 12812210
TI  - Author and subject indexes volumes 260-271 (2002).

PMID- 12812212
TI  - Multi-slice/helical computed tomography for lung cancer screening.
AB  - Compared to chest radiography, multislice/helical computed tomography (CT) is
      able to detect lung cancers of smaller size and at an earlier stage, when better
      outcomes may be possible. However, the rate of detecting benign lung nodules is
      high using these technologies. False positives can result in undue anxiety and/or
      additional tests that may be invasive and expensive. Currently evidence does not
      exist to suggest that detecting early stage lung cancer reduces mortality.
      Randomized controlled trials are underway to investigate this issue. Presently,
      even for smokers, screening for lung cancer with multi-slice/helical CT would be
      premature.

PMID- 12812213
TI  - Lipoprotein (a) and apoliprotein (a) isoform size in thyroid disease: the quest
      for the golden fleece.

PMID- 12812214
TI  - MIB-1 index in thyroid tumors: a predictor of the clinical course in papillary
      thyroid carcinoma.
AB  - MIB-1 is useful in evaluating proliferative activity and in predicting the
      aggressiveness in a variety of tumors. To investigate if MIB-1 immunoreactivity
      can add prognostic information to conventional prognostic variables in papillary
      thyroid carcinoma (PTC), 30 PTCs were evaluated using the MIB-1 antibody. For
      comparison, 10 follicular thyroid carcinomas (FTC), 8 anaplastic thyroid
      carcinomas (ATC), and 96 follicular thyroid adenomas (FTA) were similarly
      analyzed. The median MIB-1 index was 0.5% in FTA, 1.9% in PTC, 2.7% in FTC, and
      16.2% in ATC. The 13 tumors from patients classified as having aggressive PTC
      (defined as dead from disease, persisting disease, or the occurrence of distant
      metastases) had significantly higher MIB-1 index (median, 5.4%) than the 17
      patients with nonaggressive disease (median, 1.1%). MIB-1 index 1.85% or more was
      found to be an independently significant risk factor for a less favorable
      clinical course in PTC. Because of overlap of single values the utility of MIB-1
      index as a clinical test is somewhat limited. Still, at levels where no overlap
      occurs (MIB-1 index 2 3.2% or ' 0.5%) the index seems to add information to the
      established prognostic parameters. MIB-1 index should therefore be considered in
      routine histopathology of PTC.

PMID- 12812215
TI  - Timing fetal death in the second trimester by placental examination.

PMID- 12812216
TI  - [Proceedings of the 4th National Conference on the Global Approach to the
      Oncology Patient: From innovative treatment to palliative treatment. Rimini,
      Italy, 7-9 May 2003].

PMID- 12812218
TI  - Brain Injury 5th World Congress. Stockholm, Sweden, 23-26 May 2003. Abstracts.

PMID- 12812217
TI  - Massive subchorionic hematomas: suspect thrombophilia.

PMID- 12812219
TI  - Abstracts of the British Geriatrics Society Autumn Meeting. 17-18 October 2002,
      London, United Kingdom.

PMID- 12812220
TI  - Abstracts of the 6th World Congress of Psycho-Oncology. April 23-27, 2003. Banff,
      Alberta, Canada.

PMID- 12812221
TI  - Abstracts of the 26th Annual Conference on Shock. Phoenix, Arizona, USA. June 7
      10, 2003.

PMID- 12812223
TI  - Abstracts of the Associated Professional Sleep Societies 17th Annual Meeting.
      June 3-8, 2003. Chicago, Illinois, USA.

PMID- 12812222
TI  - Recent developments in medicine and law.
AB  - This article focuses on certain noteworthy legislation and cases affecting
      medicine and law during the period September 1, 2001, to August 31, 2002. It does
      not attempt to discuss every case or piece of legislation, but instead seeks to
      summarize some of the more significant developments in this area of law.

PMID- 12812224
TI  - Abstracts of the 16th International Conference on Oral and Maxillofacial Surgery.
      Athens, Greece.

PMID- 12812225
TI  - Recent developments in workers' compensation and employers' liability law.

PMID- 12812226
TI  - cDNA sequence encoding immunoglobulin M heavy chain of the mandarin fish
      Siniperca chuatsi.

PMID- 12812227
TI  - U.S. to review research at hospitals for veterans: investigators cite deaths and
      broken rules.

PMID- 12812228
TI  - Possible ban on abortion technique leaves doctors uneasy.

PMID- 12812229
TI  - Cancer incidence in five continents. Volume VIII.

PMID- 12812230
TI  - Breaking bad news: a clinician's view of the literature.
AB  - In daily practice, a clinician may have to break bad news to patients and their
      families. How the patient responds depends largely on the manner in which the
      messenger conveys the news. The clinician may harbour fears of the patient's
      unpredictable emotional reactions, his or her own display of emotions, and a
      revival of bad news that he or she may have received. He or she may also feel
      ineffectual about an inability to deal with the patient's expectations for cure.
      He or she may use distancing tactics in discussing emotionally charged topics.
      The ensuing anxiety fosters an uneasy alliance in such situations. Moreover, the
      patient may question the information. This should be seen as a need for more
      information, and not as a challenge to the messenger's integrity or the validity
      of the news. Denial on the part of patients and families may indicate their
      inability to accept the news. The paucity of medical education in this area
      dictates more emphasis in teaching communication skills to medical students and
      postgraduate trainees. Receiving the news is the start of an adaptation process
      for a patient. He or she must know that there will be difficulties ahead. The
      patient and family will face them together with the clinician. The doctor will be
      available as necessary throughout the process to answer questions and provide
      support. This entails spending time to listen, hear, acknowledge the patient's
      emotions, and advocate on the patient's behalf. It is always possible to help the
      patient frame his or her fears. When the shadow of death approaches, life and
      time become more precious. Deeper meanings and clearer priorities often emerge
      for the dying person. He or she is forced to examine what makes a life
      meaningful. By sharing burdens, insight, and support, patients and professionals
      can pursue these discoveries together.

PMID- 12812231
TI  - [Aging and trends in marital status].

PMID- 12812232
TI  - Culture and physician-patient communication: a qualitative exploration of
      residents' experiences and attitudes.
AB  - BACKGROUND: Increasing evidence suggests that communication plays a central role
      in effective clinical care. To facilitate effective instruction in this domain,
      this study seeks to understand how pediatric residents approach the challenge of
      cross-cultural communication. METHODS: A convenience sample of 29 pediatric
      residents participated in five focus groups that were jointly facilitated by a
      clinical and a process expert. Discussion was stimulated using two video
      scenarios of pediatric cross-cultural communication challenges. RESULTS: Seven
      dominant categories were evident in the discussions: characteristics of culture,
      beliefs about culture, attitudes towards culture, opinions about how to build
      expertise in communication, cultural conflict, insights regarding prejudice, and
      comments about interview technique. Residents tended to view culture and
      difference as residing in patients (not in themselves), reflecting their
      assumption that western medicine is acultural. CONCLUSIONS: Residents believe
      that lack of knowledge about other cultures causes their communication
      difficulties. Our findings suggest, however, that more basic issues may underlie
      their difficulties. Residents may recognize prejudice in the abstract but fail to
      see it in their environment, and they may spend minimal time reflecting on their
      professional culture and beliefs.

PMID- 12812234
TI  - Pediatric residents' knowledge, perceptions, and attitudes towards homosexually
      oriented youth.
AB  - BACKGROUND: Pediatric residents must have clinical exposure and specific training
      to meet the health-care needs of gay, lesbian, and bisexual adolescents.
      Homosexually oriented youths have medical and psychosocial needs that these
      future pediatricians must fulfil. OBJECTIVE: This study investigated the
      knowledge and attitudes of pediatric residents in the management of gay, lesbian,
      and bisexual youth and related health-care issues. METHOD: Twenty-nine pediatric
      residents at the University of Ottawa were sent a survey questionnaire. RESULTS:
      Many respondents indicated that they experience difficulties in discussing issues
      of sexual orientation, and feel inadequately prepared to address the health-care
      needs of homosexual youth. Furthermore, respondents showed a lack of awareness
      regarding resources available to gay, lesbian, and bisexual youth in the
      community. CONCLUSION: While knowledge is limited, residents' attitudes towards
      homosexual youth are generally positive. Also, most respondents indicate an
      interest in continuing education, and in gaining more information to better serve
      their homosexually oriented adolescent patients.

PMID- 12812235
TI  - Osteonecrosis and transient osteoporosis of the hip: diagnostic and treatment
      dilemmas.

PMID- 12812236
TI  - SESAP question. Primary thrombosis of the axillary-subclavian vein.

PMID- 12812237
TI  - Waiting lists: management, legalities and ethics.

PMID- 12812238
TI  - [Abdominal complications associated with cardiac surgery. Review of a
      contemporary surgical experience and of a series done without extracorporeal
      circulation].
AB  - INTRODUCTION: To evaluate the prevalence, risk factors and morbidity associated
      with gastrointestinal (GI) complications after cardiac surgery, with and without
      cardiopulmonary bypass, we carried out a retrospective cohort study at a
      university teaching hospital. METHODS: We divided the 11,405 eligible adult
      patients into 2 groups: group A (operated on between January 1992 and June 1996)
      (4657 patients) and group B (operated on between July 1996 and December 2000)
      (6748 patients). RESULTS: We found 147 GI complications in 134 (1.2%) patients.
      The incidence of GI morbidity was similar for the 2 groups of patients (group A,
      n = 59/4657 [1.2%]; group B, n = 75/6748 [1.1%]. Patients from group B were
      older, obese, diabetic and presented with more peripheral and cerebrovascular
      disease. Bleeding, gastritis and ulcer with perforation, the most common of these
      GI events, were associated with the esophagus and stomach (67/147 [45.5%]). Other
      events that we documented included cholecystitis 10 (6.8%), pancreatitis 13
      (8.8%), episodes of small and large bowel ischemia 17 (11.6%), pseudomembranous
      colitis 12 (8.3%) and diverticulitis 5 (3.4%). Mesenteric ischemia was
      responsible for 11 (37.9%) of the 29 deaths. Two hundred and ninety-three
      patients were revascularized without extracorporeal circulation during this
      study. In this group, we were able to pinpoint 5 (1.7%) GI complications with 3
      cases of mesenteric ischemia. Multivariate analysis identified renal
      insufficiency, prolonged intubation and sepsis as significant, predictive
      variables of GI complications for the 2 groups of patients whereas the Parsonnet
      score and stroke were predictive for the second group. CONCLUSIONS: Although
      cardiac surgery is now being performed on older patients with significant
      comorbidity, we could not demonstrate a significant increase of GI complications
      after cardiac surgery. Off-pump coronary artery bypass does not seem to protect
      patients from these complications.

PMID- 12812239
TI  - A biomechanical study in cadavers of cast boots used in the early postoperative
      period after first metatarsophalangeal joint arthrodesis.
AB  - OBJECTIVES: To compare the effectiveness of 3 common models of walking boots
      (Walkabout, Samson Walker and Equalizer Premium Walker) to that of a fibreglass
      cast in protecting an arthrodesis of the first metatarsophalangeal (MTP) joint in
      the early postoperative period, we carried out a biomechanical study in cadavers
      in the bioengineering laboratory at Memorial University of Newfoundland. METHODS:
      Two cadaver models of a first MTP joint arthrodesis were prepared by placing a
      strain gauge at the joint. This provided a measure of the bending moment across
      the fusion site. Walking was simulated by applying a force to the sole of the
      cadaver foot at multiple positions from heel to toe, representing the stages of
      gait from heel strike to toe off. RESULTS: For both cadaver specimens, the
      Walkabout boot had the lowest mean moment. The Walkabout and Sampson Walker boots
      were better than the Equalizer Premium Walker boot and the fibreglass cast (p <
      0.05), but the Walkabout boot was the best (p < 0.05). Also, for both specimens,
      the Walkabout boot had the smallest absolute maximum moment (p < 0.05).
      CONCLUSION: On a first MTP joint arthrodesis site, removable cast boots provide
      the same, if not more, reduction of force as a traditional cast.

PMID- 12812240
TI  - Distinguishing transient osteoporosis of the hip from avascular necrosis.
AB  - INTRODUCTION: To review the circumstances surrounding the misdiagnosis of
      transient osteoporosis of the hip (TOH) as avascular necrosis (AVN) and to
      increase physician awareness of the prevalence and diagnosis of this condition in
      young men, we reviewed a series of cases seen in the orthopedic unit at St.
      Michael's Hospital, University of Toronto. METHODS: We studied the charts of
      patients with TOH referred between 1998 and 2001 with a diagnosis of AVN for
      demographic data, risk factors, imaging results and outcomes. RESULTS: Twelve
      hips in 10 young men (mean age 41 yr, range from 32-55 yr) were identified. Nine
      men underwent magnetic resonance imaging (MRI) before referral, which showed
      characteristic changes of TOH. All 10 patients were referred for surgical
      intervention for a diagnosis of AVN. The correct diagnosis was made after
      reviewing patients' charts and the scans and was confirmed by spontaneous
      resolution of both symptoms and MRI findings an average of 5.5 months and 7.5
      months, respectively, after consultation. CONCLUSIONS: Despite recent
      publications, the prevalence of TOH among young men is still overlooked and the
      distinctive MRI appearance still misinterpreted. Symptoms may be severe but
      resolve over time with reduced weight bearing. The absence of focal changes on
      MRI is highly suggestive of a transient lesion. A greater level of awareness of
      this condition is needed to differentiate TOH from AVN, avoiding unnecessary
      surgery and ensuring appropriate treatment.

PMID- 12812241
TI  - Triple major curves in children.
AB  - INTRODUCTION: The predominant classification systems for scoliosis have been
      based either on etiology or curve pattern. Traditionally triple curves have not
      been included in either classification system. METHODS: We reviewed the records
      of all children with an idiopathic triple scoliotic curve seen between 1988 and
      2001 at the Children's Hospital of Eastern Ontario, Ottawa, a major pediatric
      referral centre. The triple curve had 3 structural curved segments in accordance
      with the classification of Lenke and associates. Scoliosis was defined by a curve
      greater than 10 degrees, and the apical vertebra was determined according to
      Scoliosis Research Society guidelines. Laterality of the curve was determined
      from the curve with the greatest magnitude. Curve progression was an increase in
      magnitude of at least 5 degrees. Management included observation, with bracing if
      any curve progressed to greater than 20 degrees. Surgery was reserved for curves
      that were unstable, rapidly progressive and greater than 45 degrees-50 degrees.
      RESULTS: Thirteen children (9 girls, 4 boys) were treated for a triple scoliosis
      curve. The average age at the time the triple curve developed was 13 years and 9
      months (range from 9 yr 1 mo-17 yr 5 mo). The average follow-up was 3 years and 6
      months (range from 1-11 yr). One child required spinal fusion, and 6 years
      postoperatively the curve was stable with a good fusion mass. Of the remaining
      children, 2 were treated with an orthosis and 10 with observation. CONCLUSION:
      The triple major curve is a neglected curve pattern that should be included in
      classifications of scoliosis.

PMID- 12812242
TI  - Orthopedic injuries associated with backyard trampoline use in children.
AB  - INTRODUCTION: Trampolining on an outdoor oval or circular trampoline is a popular
      activity for children but is associated with a number of orthopedic injuries,
      especially in children between the ages of 5 and 15 years. In this paper we
      review the orthopedic injuries in children associated with backyard trampoline
      use, through our experience with a series of children admitted to the Winnipeg
      Children's Hospital, the only tertiary care pediatric centre in Manitoba.
      METHODS: We reviewed the charts, x-ray films and operative reports for 80
      children under 16 years old (mean 9 yr, with 14 [18%] children between 2 and 4
      yr) with an orthopedic injury sustained when using a trampoline in the backyard.
      We noted the mechanism of injury and type and severity of orthopedic injury
      sustained. RESULTS: Fifty-two (65%) children were injured on the trampoline mat,
      and 24 (30%) were injured when they were ejected from the trampoline. Sixty (75%)
      children sustained a fracture or fracture-dislocation. Forty-eight (80%)
      orthopedic injuries occurred in the upper extremity. No child died as a result of
      a trampoline injury. CONCLUSION: The use of the "backyard" trampoline by young
      children can cause significant orthopedic injury.

PMID- 12812243
TI  - Musculoskeletal images. Knee-joint tuberculosis.

PMID- 12812244
TI  - Soft-tissue images. Splenic littoral cell angioma.

PMID- 12812245
TI  - Musculoskeletal case 28. Subsynovial hemangioma.

PMID- 12812246
TI  - Soft-tissue case 51. Gossypiboma.

PMID- 12812247
TI  - Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 6.
      "GERD" as a risk factor for esophageal cancer. Symptomatic gastroesophageal
      reflux as a risk factor for esophageal adenocarcinoma.

PMID- 12812248
TI  - Geriatric trauma: resource use and patient outcomes.
AB  - INTRODUCTION: Elderly patients who suffer trauma have a higher mortality and use
      disproportionately more trauma resources than younger patients. To compare these
      2 groups and determine the outcomes and characteristics of elderly patients, we
      reviewed patients in these 2 groups admitted and treated in our tertiary care
      provincial trauma centre. METHODS: From the provincial trauma registry we
      selected a cohort of 40 geriatric patients (group 1) (> or = 65 yr of age) with
      an ISS of 16 or more who were admitted to and spent time in our trauma service
      for more than 48 hours and compared them with a similar randomly selected cohort
      of 44 patients (group 2) aged 20-30 years. Family physicians were contacted for
      follow-up of these patients 2 years after discharge. We considered length of
      hospital stay, complications, disposition of the patients and use of consultation
      services. RESULTS: Patients in group 1 had a mean age of 72.1 years (range from
      65-98 yr) and a mean ISS of 27.3 (range from 17-50). Patients in group 2 had a
      mean age of 26.3 years (range from 22-29 yr) and a mean ISS of 26.3 (range from
      17-54). Hospital stay was significantly longer in the group 1: 34.5 days (95%
      confidence interval [CI]: 24-44 d) versus 21.6 days (95% CI: 15-28 d). More
      elderly patients experienced complications (35 v. 13, p < 0.001) and required
      medical consultations (35 v. 26, p < 0.001). In-hospital death rates were 8% (3
      of 40) and 4% (2 of 44) respectively (p = 0.3). Fewer geriatric patients could be
      discharged home (35% [14 of 40] v. 27% [22 of 44], p = 0.056) or to
      rehabilitation facilities (28% [11 of 40] v. 34% [15 of 44], p = 0.3). Five
      geriatric patients were discharged to nursing homes (p = 0.007). Of the geriatric
      patients discharged to rehabilitation facilities or home, 75% were independent 2
      years after discharge. CONCLUSIONS: Aggressive care for geriatric trauma patients
      is warranted, and resources should be directed toward rehabilitation. Based on
      our findings, we expect that creating a directed care pathway for these patients,
      targetting complications and earlier discharge, will further improve their
      outcomes.

PMID- 12812250
TI  - Avoiding stitch abscesses in subcuticular skin closures: the L-stitch.
AB  - A potential problem with the standard method of skin closure in pediatric surgery
      is the development of a skin abscess. To avoid this problem, we introduce a new
      stitch--the L-stitch. The technique involves passing the suture subcuticularly at
      the end of the incision and redirecting the needle at a 90 degree angle from the
      previous suture, before bringing it out to the skin surface. This stitch can be
      used in place of the initial and finishing knot of a running suture. It takes
      less time to perform than a square or a surgeon's knot and is less bulky. This
      technique is straightforward and, when used in conjunction with adhesive skin
      closure strips, provides strong, reliable skin closure, yielding excellent
      cosmetic results.

PMID- 12812249
TI  - Prophylactic beta-blockade to prevent myocardial infarction perioperatively in
      high-risk patients who undergo general surgical procedures.
AB  - INTRODUCTION: The benefit of administering beta-adrenergic blocking agents
      perioperatively to surgical patients at high risk for myocardial ischemia has
      been demonstrated in several well-designed randomized controlled trials. These
      benefits have included a reduction in the incidence of myocardial complications
      and an improvement in overall survival for patients with evidence of or at risk
      for coronary artery disease (CAD). We designed a retrospective study at the
      Ottawa Civic Hospital to investigate the use of beta-blockers in the
      perioperative period for high-risk general surgery patients who underwent
      laparotomy and to explore the reasons for failure to prescribe or administer beta
      blockers when indicated. METHODS: All 236 general surgery patients over the age
      of 50 years who underwent laparotomy for major gastrointestinal surgery between
      Jan. 1, 2001, and Dec. 31, 2001, were assigned a cardiac risk classification
      using the risk stratification described by Mangano and colleagues. The
      perioperative prescription and administration of beta-blockers were noted as were
      the patient's heart rate and blood pressure parameters for the first
      postoperative week, in-hospital adverse cardiac events and death. RESULTS: Of the
      143 patients classified as being at risk for CAD or having definite evidence of
      CAD, 87 (60.8%) did not receive beta-blockers perioperatively. Of those who did,
      43 were previously on beta-blockers and 13 had them ordered preoperatively.
      Patients with definite CAD were significantly more likely than others to receive
      beta-blockers perioperatively (p < 0.001), as were patients seen by an
      anesthesiologist or an internist preoperatively (p < 0.001). Twenty (33%) of the
      61 patients who were already taking beta-blockers preoperatively had them
      inappropriately discontinued postoperatively. Once prescribed by the physician,
      beta-blockers were administered by the nurses irrespective of nil par os status.
      The mean heart rate and blood pressure parameters for patients receiving beta
      blockers postoperatively was 82 beats/min and 110 mm Hg, respectively, and these
      values were not significantly different from the mean heart rate of patients not
      receiving beta-blockers. The number of postoperative cardiac events was
      significantly higher in patients with definite evidence of CAD, and among this
      group, the use of beta-blockers was associated with a significant reduction in
      postoperative cardiac events. This was not true for patients at risk for CAD or
      patients with no risk of CAD. CONCLUSIONS: A significant proportion (> 60%) of
      general surgery patients who were identified as having definite evidence of, or
      being at risk for, CAD were not prescribed beta-blockers preoperatively. More
      than 30% of patients who were on beta-blockers preoperatively did not have them
      reordered postoperatively. These results may reflect controversy surrounding the
      recommendations, miscommunication between surgeons and anesthesiologists and
      errors in postoperative ordering.

PMID- 12812251
TI  - The effect of internal CO2 conductance on leaf carbon isotope ratio.
AB  - We estimated internal CO2 conductance (gi) for C3 plant species of different life
      forms (annual herbs, deciduous trees and evergreen trees) grown in a variety of
      environments to examine the effect of gi on their leaf carbon isotope ratio
      (delta13C). The purpose of this study was to test the validity of using delta13C
      as an index of photosynthetic water use efficiency (WUE). When comparing
      deciduous tree species grown in contrasting light environments, there was a
      strong positive relationship between delta13C and WUE. Similarly, delta13C was
      positively correlated to WUE when comparing the different species of evergreen
      trees. However, the difference in WUE between evergreen and deciduous tree
      species did not relate to that in leaf delta13C. In addition, WUE was similar
      between highland and lowland herbaceous plants, although the former had a much
      higher delta13C. The positive relationship between delta13C and WUE did not hold
      across different life forms and different altitudes when differences in gi did
      not relate to those in stomatal conductance, resulting in independence of
      chloroplast CO2 partial pressure from intercellular CO2 partial pressure.

PMID- 12812252
TI  - Potential for assessing long-term dynamics in soil nitrogen availability from
      variations in delta15N of tree rings.
AB  - Numerous researchers have used the isotopic signatures of C, H, and O in tree
      rings to provide a long-term record of changes in the physiological status,
      climate, or water-source use of trees. The frequently limiting element N is also
      found in tree rings, and variation in its isotopic signature may provide insight
      into long-term changes in soil N availability of a site. However, research has
      suggested that N is readily translocated among tree ring of different years; such
      infidelity between the isotopic compositions of the N taken up from the soil and
      the N contained in the ring of that growth year would obscure the long-term N
      isotopic record. We used a 15-year 15N-tracer study to assess the degree of N
      translocation among tree rings in ponderosa pine (Pinus ponderosa) trees growing
      in a young, mixed-conifer plantation. We also measured delta13C and delta15N
      values in unlabeled trees to assess the degree of their covariance in wood
      tissue, and to explore the potential for a biological linkage between them. We
      found that the maximum delta15N values in rings from the labeled trees occurred
      in the ring formed one-year after the 15N was applied to the roots. The delta15N
      value of rings from labeled trees declined exponentially and bidirectionally from
      this maximum peak, toward younger and older rings. The unlabeled trees showed
      considerable interannual variation in the delta15N values of their rings (up to 3
      and 5 per thousand), but these values correlated poorly between trees over time
      and differed by as much as 6 per thousand. Removal of extractives from the wood
      reduced their delta15N value, but the change was fairly small and consistent
      among unlabeled trees. The delta13C and delta15N values of tree rings were
      correlated over time in only one of the unlabeled trees. Across all trees, both
      delta13C values of tree rings and annual stem wood production were well
      correlated with annual precipitation, suggesting that soil water balance is an
      important environmental factor controlling both net C gain and transpirational
      water loss at this site. Our results suggest that interannual translocation of N
      among tree rings is substantial, but may be predictable enough to remove this
      source of variation from the tree-ring record, potentially allowing the
      assessment of long-term changes in soil N availability of a site.

PMID- 12812253
TI  - Nitrogen stable isotope composition of leaves and roots of plants growing in a
      forest and a meadow.
AB  - In controlled N-nutrition experiments, differences in delta15N composition of
      leaves and roots are regularly found. In this paper we report results from a
      survey of nitrogen stable isotope signatures of leaves and roots of 16 plant
      species growing under natural conditions in a meadow and a forest understorey,
      which differed in nitrate and ammonium availability. Significant differences
      between leaf and root were observed. The range of delta15N [leaf-root] values was
      -0.97 to +0.86 per thousand, small compared to published values from controlled N
      nutrition experiment, but almost as large as the range of leaf delta15N values (
      1.04 to +1.08 per thousand). Forbs showed the largest differences between leaves
      and roots and showed a significant difference with respect to habitat. Grasses
      and legumes did not show significant differences in delta15N [leaf-root] between
      the two habitats. Care must be taken when using leaf delta15N values as
      representative for whole-plant 15N composition in these two habitats.

PMID- 12812254
TI  - Tree species of the Central Amazon and soil moisture alter stable isotope
      composition of nitrogen and oxygen in nitrous oxide evolved from soil.
AB  - The use of stable isotopes of N and O in N2O has been proposed as a way to better
      constrain the global budget of atmospheric N2O and to better understand the
      relative contributions of the main microbial processes (nitrification and
      denitrification) responsible for N2O formation in soil. This study compared the
      isotopic composition of N2O emitted from soils under different tree species in
      the Brazilian Amazon. We also compared the effect of tree species with that of
      soil moisture, as we expected the latter to be the main factor regulating the
      proportion of nitrifier- and denitrifier-derived N2O and, consequently, isotopic
      signatures of N2O. Tree species significantly affected delta15N in nitrous oxide.
      However, there was no evidence that the observed variation in delta15N in N2O was
      determined by varying proportions of nitrifier- vs. denitrifier-derived N2O. We
      submit that the large variation in delta15N-N2O is the result of competition
      between denitrifying and immobilizing microorganisms for NO3(-). In addition to
      altering delta15N-N2O, tree species affected net rates of N2O emission from soil
      in laboratory incubations. These results suggest that tree species contribute to
      the large isotopic variation in N2O observed in a range tropical forest soils. We
      found that soil water affects both 15N and 18O in N2O, with wetter soils leading
      to more depleted N2O in both 15N and 18O. This is likely caused by a shift in
      biological processes for 15N and possible direct exchange of 18O between H2O and
      N2O.

PMID- 12812255
TI  - How important are columnar cacti as sources of water and nutrients for desert
      consumers? A review.
AB  - Succulent CAM plants, such as columnar cacti, are important physiognomic elements
      of many arid lands. Although, these plans are often ecologically important
      because they provide abundant resources in the form of nectar and fruit, their
      contribution to the energy, nutrient and water budgets of consumes has not been
      quantified. We describe an isotopic approach that allows quantifying the
      ecological importance of CAM succulents. We first briefly review our work on the
      interaction between saguaros, an archetypical CAM succulent, and the desert doves
      that feed on its fruit. We then describe the potential importance of saguaro
      fruit as a function of its abundance, macronutrient composition, and seasonal
      availability. We argue that the resources provided by saguaros do much to satisfy
      the energy and water requirements of the birds that reside in hot subtropical
      deserts during the summer. We then describe the carbon isotope composition of
      saguaros and of the plant community in which they are imbedded and use two
      species of desert doves to illustrate how stable isotopes can reveal the
      importance of a single plant as a source of carbon and water for consumers. The
      second section of this review presents new data on the importance of saguaros for
      the entire community of birds that inhabit the Sonoran Desert during the summer.
      We show how the resources of saguaro reach across dietary guilds and account for
      a large proportion of the diet of many insectivorous species as well as that of
      granivorous and frugivorous species. We demonstrate that many of these species
      probably obtain significant water as well as nutrients from saguaro fruit.
      Finally, we point out the current limitations of using deuterium as a water
      tracer in animal systems.

PMID- 12812256
TI  - Physiological condition and water source use of Sonoran Desert riparian trees at
      the Bill Williams River, Arizona, USA.
AB  - We investigated the environmental water sources used in mid-summer by three
      Sonoran Desert phreatophytic riparian tree species, Salix gooddingii, Populus
      fremontii, and the exotic Tamarix spp., at sites that differed in water table
      depth. Salix gooddingii was most sensitive to water table decline, as evidenced
      by lower predawn water potentials. Although P. fremontii was less sensitive to
      water table decline than S. gooddingii, its leaf gas exchange was the most
      responsive to atmospheric water stress imposed by high leaf-to-air vapor pressure
      deficit. Tamarix spp. was least sensitive to water table decline and showed no
      reduction of predawn water potential over the measured range of depth to
      groundwater. Comparison between D/H of xylem and sampled environmental water
      sources suggest that S. gooddingii and P. fremontii used groundwater at most
      sites with no change in water source as depth to groundwater varied. In contrast,
      xylem D/H of Tamarix spp. was depleted in deuterium compared to groundwater at
      most sites, suggesting use of water from an unsampled source, or discrimination
      against deuterium during water uptake. This study highlights the difficulty in
      sampling all water sources in large-scale studies of riparian ecosystems with
      complex subsurface hydrogeology.

PMID- 12812257
TI  - Laboratory quality control: using patient data to assess analytical performance.
AB  - Quality control plays a vital role helping to ensure the reliability of
      laboratory test results. The application of statistical quality control has been
      a component of laboratory medicine for approximately 50 years. Many of the
      control rules based on the early applications of statistical quality control have
      remained essentially unchanged since their initial introduction. Optimization of
      quality control rules can vary depending on the application for which a test is
      to be used. This review explores the various applications of laboratory quality
      control procedures and their role in identifying laboratory error. The ubiquitous
      use of computers in today's laboratories has enabled the development of more
      sophisticated means of assessing laboratory quality. The use of the Six Sigma
      technique and its adoption by the laboratory community is one example. Other
      examples include the use of patient-derived quality control procedures as a means
      of assessing laboratory performance. Early examples of these types of
      applications include use of Bull's algorithm, anion gap measurements, and delta
      checking. More recent applications include the correlation of laboratory test
      results, the average of normals procedure, and the Bhattacharya method.

PMID- 12812258
TI  - The common polymorphism of apolipoprotein E: geographical aspects and new
      pathophysiological relations.
AB  - Apolipoprotein E (apoE) has important functions in systemic and local lipid
      transport, but also has other functions. The gene (APOE) shows a common
      polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies
      vary substantially around the world, but APOE*3 is the most common almost
      everywhere and is often considered to be the ancestral or "wild-type" allele for
      that reason. However, there are several arguments for APOE*4 being the ancestral
      allele. But then, why has APOE*3 become so frequent? And why has APOE*4 not
      become extinct? The proportion of APOE*4 carriers increases from only 10-15% in
      southern Europe to 40-50% in the north. The gradient may be a trace of the demic
      expansion of agriculture that began about 10,000 years ago, but it may also
      reflect the possibility that APOE*4 carriers are less likely to develop vitamin D
      deficiency. The common APOE polymorphism is associated with varying risk of
      cardiovascular disease and Alzheimer's disease, but other interesting aspects may
      emerge in the future.

PMID- 12812259
TI  - Pentanucleotide TTTTA and G/A -914 DNA polymorphisms in apolipoprotein(a)
      promoter: genotyping by single-tube PCR.
AB  - It is known that pentanucleotide repeat polymorphism, consisting of varying
      number of (TTTTA) repeats in a promoter, is associated with plasma lipoprotein(a)
      levels. G/A -914 base substitution has also been correlated with pentanucleotide
      repeat polymorphism in individuals with high and low lipoprotein(a) levels. To
      facilitate future analysis of these polymorphisms we have developed a quick and
      reliable assay for the detection of both polymorphisms in a single polymerase
      chain reaction.

PMID- 12812260
TI  - Study of apo(a) length polymorphism and lipoprotein(a) concentrations in subjects
      with single or double apo(a) isoforms.
AB  - Cardiovascular risk is associated with high lipoprotein(a) (Lp(a)) concentrations
      and low molecular weight apolipoprotein(a) (apo(a)) isoforms. We studied the
      relationship between these two biological parameters, particularly in subjects
      expressing two apo(a) isoforms. Plasma Lp(a) was measured by immunonephelometry
      in 530 unrelated Caucasian patients at high cardiovascular risk, and apo(a) size
      determined by immunoblotting using a recombinant standard. Two, one, or no apo(a)
      isoforms were detected in 258, 270, and 2 subjects, respectively. Lp(a)
      concentrations showed a non-Gaussian distribution, being higher in the 'double
      band' than in the 'single band' group (median 0.42 vs. 0.11 g/l, p < 0.0005).
      Apo(a) size distribution was bimodal, with two frequency peaks at 18 kringles (K)
      and 27 K. Small size apo(a) isoforms were more frequently found in the 'double
      band' group, where major isoforms were of lower size than minor isoforms (median
      20 vs. 27 K). Regression analysis showed that apo(a) gene length accounted for
      33% of Lp(a) variation, with a threshold effect at 20 K, no correlation being
      found over this value. The minor apo(a) isoform did not significantly influence
      Lp(a) concentration. These data confirm the relationship between apo(a) size and
      Lp(a) concentration and suggest that the assessment of cardiovascular risk should
      take into account the threshold effect at 20 K and the absence of influence of
      the minor apo(a) isoform.

PMID- 12812261
TI  - Early detection of peritonitis in continuous ambulatory peritoneal dialysis
      patients by cytokine measurements.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) carries a risk of peritonitis
      which is accompanied by mild symptomatology. Culture of effluent has yielded
      organism in 50% of cases. Peritoneal phagocytes produce tumor necrosis factor
      alpha and interleukin (IL)-1 in response to contact with bacteria, initiating an
      inflammatory cascade which leads to IL-6 and IL-8 secretion. Additonally,
      neutrophils undergo an increase in oxidative metabolism. We have evaluated the
      diagnostic accuracy of effluent measurements of TNF-alpha, IL-6, IL-8, and
      oxidative metabolism markers in these patients. Dialysate fluids (n = 65) were
      collected from non-infected patients and those presenting with acute peritonitis.
      Positive culture proved the diagnosis. Oxidative markers and nitric oxide were
      measured by chemiluminescence. Cytokines were measured by solid phase
      chemiluminescent immunometric assay (Immulite, DPC, USA). Receiver operating
      characteristic (ROC) curves were used to assess the diagnostic accuracy and the
      areas under curves were calculated for comparison. All effluent cytokines and
      oxidative markers were significantly higher in patients with peritonitis when
      compared to those without (p < 0.05). Significant correlations were evident
      between IL-6 and IL-8, lucigenin chemiluminescence and luminol chemiluminescence,
      lucigenin chemiluminescence and IL-6 or IL-8, and luminol chemiluminescence and
      IL-6 or IL-8. ROC curves showed that the ability of IL-6, IL-8, lucigenin
      chemiluminescence, and luminol chemiluminescence to differentiate CAPD patients
      with peritonitis from non-infected cases exceeds that of polymorphonuclear
      leukocyte count.

PMID- 12812262
TI  - Hematopoietic growth factors in colorectal cancer patients.
AB  - Hematopoietic growth factors (HGFs) are involved in the regulation of growth and
      spread of cancer. Therefore, in the present study, we have investigated in
      colorectal cancer patients the serum levels of selected HGFs, such as stem cell
      factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating
      factor (GM-CSF), and M-CSF in relation to controls and to the classical tumor
      markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA
      19-9) in colorectal cancer. Additionally, we have compared the serum levels of
      cytokines with tumor site and stage and other clinical characteristics such as
      age and sex. We also defined the receiver-operating characteristics (ROC) curve
      for HGFs and classical tumor markers. The tested cytokines were measured in 70
      patients with colorectal cancer and in 40 healthy subjects. HGFs were determined
      using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by
      microparticle enzyme immunoassay. There were significant differences in the
      levels of circulating SCF, IL-3, M-CSF, GM-CSF, and CEA and CA 19-9 in the
      colorectal cancer patients compared to the control group. The levels of M-CSF and
      CEA were significantly higher in patients with a more advanced tumor stage. The
      significant positive correlation was observed between the CEA and CA 19-9
      concentrations. The M-CSF serum levels correlated positively with the tested
      tumor markers. The M-CSF area under the ROC curve was the largest. These results
      suggest that M-CSF is, among the tested HGFs, the best candidate for a colorectal
      cancer tumor marker.

PMID- 12812263
TI  - Chylomicron remnant concentrations in patients with coronary artery disease.
AB  - Persisting chylomicron remnants have been linked to premature atherosclerosis.
      The analysis of chylomicron remnant concentrations by an oral triglyceride
      tolerance test, however, is time-consuming for the study subjects and requires
      large resources in the laboratory. Therefore, only small numbers of subjects have
      been studied in the past. The aim of this study was to elucidate the prevalence
      of elevated chylomicron remnants, to identify effectors of chylomicron remnant
      clearance and to compare chylomicron remnants in the prediction of coronary
      artery disease with other risk factors. We applied a novel oral triglyceride
      tolerance test to 423 patients (368 males, 55 females) with a confirmed diagnosis
      of coronary artery disease (CAD) and to 390 control subjects (295 males, 95
      females) in a case-control setting. This study revealed that elevated chylomicron
      remnant concentrations (retinyl esters > 1.5 micromol/l) are present in 20% of
      all subjects. Male gender, the apolipoprotein E2 isoform, and higher body mass
      index were associated with increased chylomicron remnant concentrations. However,
      chylomicron remnants were lower and plasma triglycerides higher in patients with
      CAD. We conclude that screening for a delayed clearance of chylomicron remnants
      is of little clinical value in CAD.

PMID- 12812264
TI  - Follicular fluid renin concentration in patients with polycystic ovaries treated
      with gonadotrophins in an in vitro fertilisation programme.
AB  - The initial hypothesis was that the follicular fluid prorenin concentration was
      higher in women with polycystic ovaries (PCO) compared to normally cycling women
      stimulated by gonadotrophins. In a controlled prospective study, 47 women
      undergoing in vitro fertilisation (IVF) were enrolled: 20 women with PCO
      represented the study group and 27 normally cycling women the control group.
      Plasma prorenin, active renin, serum oestradiol, and androstenedione
      concentrations were measured on the day of human chorionic gonadotrophin (HCG)
      administration and 36 hours after HCG administration. Follicular fluid prorenin,
      active renin, oestradiol, and androstenedione concentrations from the dominant
      follicle and pooled follicles were measured 36 hours after HCG administration.
      Plasma prorenin concentration 36 hours after HCG administration was significantly
      higher in the PCO group (1867 microU/l; range 1137-3162 microU/l) than in
      controls (860 microU/l; range 433-1763 microU/l) (p = 0.007). The follicular
      fluid prorenin concentration in the dominant follicle and in the pooled follicles
      was lower in the PCO group (20190 microU/l; range 11130-25955 microU/l) than in
      controls (46930 microU/l; range 20671-66171 microU/l) (p = 0.003). We conclude
      that plasma prorenin concentrations in gonadotrophin-stimulated PCO cycles are
      augmented due to numerous follicles. Lower follicular fluid prorenin
      concentrations in women with PCO show that the synthesis of prorenin in theca
      cells starts later after HCG administration than in normally cycling women.

PMID- 12812265
TI  - Utilization of common inflammatory markers in new, symptomatic, primary care
      outpatients based on their cost-effectiveness.
AB  - Few studies have demonstrated the optimal usage of common inflammatory markers,
      alone or in combination, based on the cost-effectiveness. We analyzed the yield
      and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte
      sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new
      primary care outpatients with inflammation-related symptoms. A useful result (UR)
      was assigned if tests contributed to a change in physician's diagnosis or
      decision-making. Costs of testing were calculated based on either single or
      simultaneous measurement. Five inflammatory markers generated 147 URs in 123
      patients. CRP showed the best contribution to generation of UR, followed by
      sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor
      correlation with WBC (r = 0.458), while sialic acid strongly correlated with
      total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r
      = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC
      produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or
      Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated
      multichannel analyzer-based test, demonstrated the favorable cost-effectiveness
      over ESR or protein fractionation when combined with CRP (and WBC). Our results
      indicate that the optimal usage of these inflammatory markers should involve
      careful cost-effectiveness considerations.

PMID- 12812266
TI  - Hyperhomocysteinemia and end-stage renal disease: determinants and association
      with cardiovascular disease in Tunisian patients.
AB  - The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients
      with chronic renal failure (CRF) and those treated with hemodialysis (HD) and
      renal transplant (RT). The aims of the study were to identify the determinants of
      tHcy concentration and to test the association between hyperhomocysteinemia and
      atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF
      patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31
      age- and sex-matched healthy subjects were included. Plasma tHcy was assessed by
      a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to
      identify the main determinants of tHcy concentration and to assess the
      relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean
      tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean
      +/- SD) (28.9 +/- 9.8 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and
      in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1
      micromol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that
      tHcy was significantly higher in males (p = 0.02), and was related to age (p =
      0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and
      creatinine clearance (p = 0.0008). However, tHcy was not associated with C
      reactive protein and did not significantly differ between CRF, HD, or RT
      patients. The upper quartile of tHcy concentration was significantly associated
      with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09;
      95% CI, 1.11-8.61; p = 0.01). This association remained significant after
      adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95%
      CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher
      in ESRD patients than in subjects with normal renal function. This increase could
      be related to glomerular filtration rate reduction and functional B vitamins
      deficiency, but was not associated with inflammation. The upper quartile of tHcy
      concentrations confers 4.78-fold increased independent risk for atherothrombotic
      events in ESRD patients.

PMID- 12812267
TI  - Folate and cobalamin levels as determinants of plasma homocysteine in different
      age groups of healthy controls and psychogeriatric patients.
AB  - Homocysteine (Hcy) is the demethylated derivate of methionine and can be
      metabolized by two pathways. It is either catabolized by the transulfuration
      pathway to cysteine or remethylated to methionine mainly by the folate- and
      cobalamin-dependent enzyme methionine synthase. Previous findings suggest that
      folate is the most important vitamin determinant of plasma total homocysteine
      (tHcy) concentration but also that the relation between plasma tHcy levels and
      levels of cobalamin and folate in the circulation might differ in different
      populations. In the present study, we have analyzed these parameters in different
      age groups of healthy subjects and psychogeriatric patients, who are known to
      have increased plasma tHcy. The present study shows that serum cobalamin
      concentration is a more important determinant of plasma tHcy concentration than
      blood folate concentration in the age groups <65 years in both psychogeriatric
      patients and control subjects, whereas with increasing age blood folate
      concentration becomes the most important vitamin determinant. The findings of
      increased plasma tHcy with folate being the main vitamin determinant in the
      oldest age groups of patients and controls, suggest that tissue levels of folate
      in elderly subjects are too low and that vitamin supplementation should be given.

PMID- 12812269
TI  - Requirements for reproducibility, trueness and error of measurement in internal
      quality control schemes.
AB  - Among the various models proposed to meet requirements for metrological
      performance in clinical laboratory measurements, that most widely used is intra-
      and inter-biological variation. However, this model has weaknesses: a) in some
      cases, intra-individual biological variation is so small that requirements based
      on such data may not be met by routine methods; b) there is great variation among
      the intra- and inter-individual biological variations themselves. We therefore
      propose integration between "state-of-the-art" methods to minimize imprecision,
      and also suggest that requirements calculated on the basis of biological
      variations should be used in setting requirements for minimizing imprecision.
      Furthermore, we describe a new scale for setting requirements from biological
      variation data and suggest that systematic error should be corrected whenever it
      is statistically significant.

PMID- 12812268
TI  - Influence of gender on circulating cardiac natriuretic hormones in patients with
      heart failure.
AB  - In order to study the influence of gender on circulating levels of cardiac
      natriuretic hormones (CNHs) in heart failure, we measured the plasma levels of
      atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by means of
      highly sensitive and specific IRMA methods in 239 consecutive patients (age 64.7
      +/- 11.6 years, range 21-89 years; 170 men and 69 women) with cardiomyopathy.
      There was different response of CNH according to gender in patients with heart
      failure, as indicated by the ratio between the individual CNH values of patients
      and the gender-specific cut-off values. Indeed, the mean ratio for ANP found in
      men (3.6 +/- 3.6) was significantly higher (p = 0.0075) than that found in women
      (2.4 +/- 2.1). The mean ratio for BNP was on average 2.3 fold higher (15.9 +/-
      27.1 in men and 6.9 +/- 6.8 in women, p = 0.0084). Moreover, age, ejection
      fraction, and disease severity independently and significantly contributed to
      regression with both ANP (R = 0.612, F = 39.969, p < 0.0001) and BNP (R = 0.656,
      F = 49.957, p < 0.0001) values, while gender did not. In conclusion, our study
      suggests a different, gender-specific activation of the CNH system in this
      clinical condition, although age, ejection fraction and disease severity seem to
      be more powerful predictors than gender of circulating levels of ANP and BNP in
      patients with heart failure.

PMID- 12812270
TI  - Measurements of serum S-100B protein: effects of storage time and temperature on
      pre-analytical stability.
AB  - Measurement of S-100B protein in serum or cerebrospinal fluid is increasingly
      used as a molecular marker of brain damage. However, there is no information
      about the pre-analytical in vitro stability of S-100B. We have investigated
      whether storing blood samples at different time periods and conditions affected
      the measured levels of S-100B protein. Blood samples were taken from 29
      neurosurgical patients with normal serum S-100B values and from seven patients
      with increased serum S-100B values. Blood samples were immediately divided into
      nine aliquots for measuring S-100B immediately and after 4, 8, 12, and 24 hours,
      stored at room temperature or at 4 degrees C. Measurement of S-100B was performed
      using the LIAISON assay (Byk-Sangtec Diagnostica, Dietzenbach, Germany).
      Moreover, in 10 additional patients the effect of freezing the serum and thawing
      the sample after 24 hours was investigated. There were no differences between the
      results of S-100B measurements after storing the sample at different temperatures
      and time periods. There was no trend towards higher or lower values in all three
      groups. Therefore, blood samples may be collected as part of the daily clinical
      routine without time constraint and even stored overnight without affecting S
      100B serum levels when measured with the LIAISON Sangtec 100 assay.

PMID- 12812271
TI  - Automated serum protein electrophoresis by Capillarys.
AB  - Capillary zone electrophoresis (CZE) of serum proteins is increasingly gaining
      impact in clinical laboratories. In this report, we evaluate automated capillary
      zone electrophoresis by Capillarys (Sebia, France). Within-run and between-run
      imprecision for the five electrophoretic fractions was <2% and <6%, respectively.
      Data obtained with Capillarys correlated with results obtained with agarose gel
      electrophoresis and Paragon CZE 2000 (Beckman Coulter, USA). Analysis of serum
      obtained from patients with inflammation, nephrotic syndrome, bisalbuminemia, and
      alpha1-antitrypsin deficiency revealed that Capillarys was able to detect these
      abnormalities. Two hundred thirty eight samples were analyzed by agarose gel
      electrophoresis, Capillarys, capillary electrophoresis using Paragon CZE 2000
      system, and immunofixation. Sample selection was based on the presence of a
      disturbed morphology (e.g., spike) of the protein profile or
      hypogammaglobulinemia on agarose gel electrophoresis and/or Capillarys.
      Immunofixation revealed the presence of a monoclonal protein, oligoclonal bands,
      polyclonal pattern, and a normal profile in, respectively, 89, 66, 19, and 64
      samples. With Capillarys, Paragon, and agarose gel electrophoresis, a spike
      and/or disturbed morphology of the profile was found in 222, 182, and 180
      samples, respectively. In these samples, immunofixation was negative in 73 (33%),
      46 (25%), and 39 (22%) samples, respectively. These data indicate that Capillarys
      has a lower specificity than agarose gel electrophoresis and Paragon 2000. Of the
      89 samples with a monoclonal protein, Capillarys, Paragon, and agarose gel
      electrophoresis failed to detect, respectively, three, three, and one monoclonal
      protein(s). Interferences by radio-opaque agents, complement degradation
      products, fibrinogen, and triglycerides are described. In conclusion, automated
      capillary zone electrophoresis with Capillarys provides for reproducible, rapid,
      and reliable serum electrophoresis.

PMID- 12812272
TI  - Using interactive software to teach image-based clinical laboratory tests in
      developing countries: a pilot trial in Nepal.
AB  - This study explores the feasibility of using computer tutorials to train
      laboratory personnel in Nepal. Training incorporated three software programs that
      teach microscope-based laboratory tests (peripheral blood smears, urinalysis,
      Gram stains). Forty-seven participants attended training sessions and completed a
      questionnaire. The participants' overall perception was: 1) the software was
      superior to formal lectures for learning image-based laboratory tests (43
      participants, 92%); 2) the software would enhance job performance (43
      participants, 92%); 3) more subjects should be taught using software (40
      participants, 85%); and 4) the software helped participants learn new materials
      (38 participants, 81%). Considering that 79% of the participants were novice
      computer users, it is noteworthy that 38 (81%) participants thought the method of
      instruction was easy to understand. Factors contributing to learning included: 1)
      the resemblance of the computer images to actual microscope images derived from
      patient samples (37 participants, 68%); 2) the use of multiple examples of cells
      and other microscopic structures (28 participants, 60%); 3) the ability to
      interact with images and animations (23 participants, 49%); 4) the step-by-step
      explanation of laboratory techniques (21 participants, 45%); and 5) the self
      pacing of the tutorial (12 participants, 26%). Overall, the pilot study suggests
      that educational software could help train clinical laboratory personnel in
      developing countries.

PMID- 12812273
TI  - Graduate and postgraduate diploma and degree programs in clinical laboratory
      sciences.

PMID- 12812274
TI  - Do isoluminant color changes capture attention?
AB  - Four experiments are reported in which the effects of peripheral cues on visual
      orienting were investigated. In the luminance condition, the cues consisted of a
      peripheral change in stimulus luminance. In the isoluminance condition, the cues
      consisted of an isoluminant color change, using the transient tritanopic
      technique. In Experiments 1 and 2, it was found that peripheral luminance cues
      captured attention, whereas peripheral isoluminance cues did not. In Experiments
      3 and 4, the participants detected a peripheral target that was also isoluminant
      with the background. Under these conditions, it was found that both luminance and
      isoluminance cues captured attention. The results are discussed in terms of the
      roles of the dorsal and ventral streams in visual orienting, and it is concluded
      that our findings provide partial support for the contingent involuntary
      orienting hypothesis of C. Folk and colleagues.

PMID- 12812275
TI  - Interactions of afterimages for orientation and color: experimental data and
      model simulations.
AB  - Sequential viewing of two orthogonally related patterns produces an afterimage of
      the first pattern. We report an experiment that quantifies some properties of
      this type of afterimage. It is shown that it is important for the two patterns to
      have orthogonal orientations and that the appearance of the afterimage does not
      depend on the spatial frequency of the second pattern. We then show that
      Grossberg's model of interacting boundary and feature contour systems can account
      for the observed properties of these afterimages.

PMID- 12812276
TI  - A diffusion model analysis of the effects of aging on brightness discrimination.
AB  - The effects of aging on decision time were examined in a brightness
      discrimination experiment with young and older subjects (ages, 60-75 years).
      Results showed that older subjects were slightly slower than young subjects but
      just as accurate. Ratcliff's (1978) diffusion model was fit to the data, and it
      provided a good account of response times, their distributions, and response
      accuracy. There was a 50-msec slowing of the nondecision components of response
      time for older subjects relative to young subjects, but response criteria
      settings and rates of accumulation of evidence from stimuli were roughly equal
      for the two groups. These results are contrasted with those obtained from letter
      discrimination and signal-detection-like tasks.

PMID- 12812277
TI  - Word identification and eye fixation locations in visual and visual-plus-auditory
      presentations of spoken sentences.
AB  - In this study, we investigated where people look on talkers' faces as they try to
      understand what is being said. Sixteen young adults with normal hearing and
      demonstrated average speechreading proficiency were evaluated under two modality
      presentation conditions: vision only versus vision plus low-intensity sound. They
      were scored for the number of words correctly identified from 80 unconnected
      sentences spoken by two talkers. The results showed two competing tendencies: an
      eye primacy effect that draws the gaze to the talkers eyes during silence and an
      information source attraction effect that draws the gaze to the talker's mouth
      during speech periods. Dynamic shifts occur between eyes and mouth prior to
      speech onset and following the offset of speech, and saccades tend to be
      suppressed during speech periods. The degree to which the gaze is drawn to the
      mouth during speech and the degree to which saccadic activity is suppressed
      depend on the difficulty of the speech identification task. Under the most
      difficult modality presentation condition, vison only, accuracy was related to
      average sentence difficulty and individual proficiency in visual speech
      perception, but not to the proportion of gaze time directed toward the talkers
      mouth or toward other parts of the talker's face.

PMID- 12812278
TI  - Gaze behavior in audiovisual speech perception: the influence of ocular fixations
      on the McGurk effect.
AB  - We conducted three experiments in order to examine the influence of gaze behavior
      and fixation on audiovisual speech perception in a task that required subjects to
      report the speech sound they perceived during the presentation of congruent and
      incongruent (McGurk) audiovisual stimuli. Experiment 1 showed that the subjects'
      natural gaze behavior rarely involved gaze fixations beyond the oral and ocular
      regions of the talker's face and that these gaze fixations did not predict the
      likelihood of perceiving the McGurk effect. Experiments 2 and 3 showed that
      manipulation of the subjects' gaze fixations within the talker's face did not
      influence audiovisual speech perception substantially and that it was not until
      the gaze was displaced beyond 10 degrees - 20 degrees from the talker's mouth
      that the McGurk effect was significantly lessened. Nevertheless, the effect
      persisted under such eccentric viewing conditions and became negligible only when
      the subject's gaze was directed 60 degrees eccentrically. These findings
      demonstrate that the analysis of high spatial frequency information afforded by
      direct oral foveation is not necessary for the successful processing of visual
      speech information.

PMID- 12812279
TI  - Seeing or hearing? Perceptual independence, modality confusions, and crossmodal
      congruity effects with focused and divided attention.
AB  - Observers were given brief presentations of pairs of simultaneous stimuli
      consisting of a visual and a spoken letter. In the visual focused-attention
      conditon, only the visual letter should be reported; in the auditory focused
      attention condition, only the spoken letter should be reported; in the divided
      attention condition, both letters, as well as their respective modalities, should
      be reported (forced choice). The proportions of correct reports were nearly the
      same in the three conditions (no significant divided-attention decrement), and in
      the divided-attention condition, the probability that the visual letter was
      correctly reported was independent of whether the auditory letter was correctly
      reported. However, with a probability much higher than chance, the observers
      reported hearing the visual stimulus letter or seeing the spoken stimulus letter
      (modality confusions). The strength of the effect was nearly the same with
      focused as with divided attention. We also discovered a crossmodal congruity
      effect: Performance was better when the two letters in a stimulus pair were the
      same than when they differed in type.

PMID- 12812280
TI  - Feature parsing: feature cue mapping in spoken word recognition.
AB  - For listeners to recognize words, they must map temporally distributed phonetic
      feature cues onto higher order phonological representations. Three experiments
      are reported that were performed to examine what information listeners extract
      from assimilated segments (e.g., place-assimilated tokens of cone that resemble
      comb) and how they interpret it. Experiment 1 employed form priming to
      demonstrate that listeners activate the underlying form of CONE, but not of its
      neighbor (COMB). Experiment 2 employed phoneme monitoring to show that the same
      assimilated tokens facilitate the perception of postassimilation context.
      Together, the results of these two experiments suggest that listeners recover
      both the underlying place of the modified item and information about the
      subsequent item from the same modified segment. Experiment 3 replicated
      Experiment 1, using different postassimilation contexts to demonstrate that
      context effects do not reflect familiarity with a given assimilation process. The
      results are discussed in the context of general auditory grouping mechanisms.

PMID- 12812281
TI  - Visual influences on the internal structure of phonetic categories.
AB  - Previous work has demonstrated that the graded internal structure of phonetic
      categories is sensitive to a variety of contextual factors. One such factor is
      place of articulation: The best exemplars of voiceless stop consonants along
      auditory bilabial and velar voice onset time (VOT) continua occur over different
      ranges of VOTs (Volaitis & Miller, 1992). In the present study, we exploited the
      McGurk effect to examine whether visual information for place of articulation
      also shifts the best exemplar range for voiceless consonants, following Green and
      Kuhl's (1989) demonstration of effects of visual place of articulation on the
      location of voicing boundaries. In Experiment 1, we established that /p/ and /t/
      have different best exemplar ranges along auditory bilabial and alveolar VOT
      continua. We then found, in Experiment 2, a similar shift in the best-exemplar
      range for /t/ relative to that for /p/ when there was a change in visual place of
      articulation, with auditory place of articulation held constant. These findings
      indicate that the perceptual mechanisms that determine internal phonetic category
      structure are sensitive to visual, as well as to auditory, information.

PMID- 12812282
TI  - Auditory imagery from musical notation in expert musicians.
AB  - Anecdotal evidence has suggested that musical notation can trigger auditory
      images. Expert musicians silently read scores containing well-known themes
      embedded into the notation of an embellished phrase and judged if a tune heard
      aloud thereafter was the original theme (i.e., melodic target) or not (i.e.,
      melodic lure). Three experiments were conducted employing four score-reading
      conditions: normal nondistracted reading, concurrent rhythmic distraction,
      phonatory interference, and obstruction by auditory stimuli. The findings
      demonstrate that phonatory interference impaired recognition of original themes
      more than did the other conditions. We propose that notational audiation is the
      silent reading of musical notation resulting in auditory imagery. The research
      suggests that it also elicits kinesthetic-like phonatory processes.

PMID- 12812283
TI  - Feeling textures through a probe: effects of probe and surface geometry and
      exploratory factors.
AB  - Vibratory roughness perception occurs when people feel a surface with a rigid
      probe. Accordingly, perceived roughness should reflect probe and surface
      geometry, exploratory speed, and force. Experiments 1 and 2 compared magnitude
      estimation of roughness with the bare finger and two types of probes, one
      designed to eliminate force moments, under the subject's active control.
      Experiments 3 and 4 varied speed under passive control. Log magnitude was
      consistently a quadratic function of log spacing between elements in the surface.
      The location of the function's peak was related to the drop point--that is, the
      spacing at which the probe can just drop between elements--which is affected by
      probe tip diameter, element height, and speed. Other parameters of the quadratic
      were affected by probe type and speed.

PMID- 12812284
TI  - Sequential priming is not constrained by the shape of long-term learning curves.
AB  - When multiple stimulus-to-response (S-R) mappings are randomly intermixed and
      repeated in a block of trials, immediate repetitions of an aspect of a stimulus
      and/or a response can facilitate stimulus detection, classification, and/or
      response selection--known as sequential priming. In addition to these short-term
      effects, response times (RT) for almost any task diminish with extended practice,
      improvements can occur over many days, and RT learning curves typically assume
      exponential or power functions. We investigated whether short-term sequential
      priming and long-term practice modulate RT through a common mechanism, using a
      variant of the additive factors method. We tracked how various priming effects,
      presumably affecting different processing stages (e.g, stimulus selection,
      stimulus identification/classification, and S-R mapping), varied over training
      sessions as RT diminished. All the priming effects either were not reduced or
      reduced approximately linearly at rates much slower than those predicted by the
      shapes of the coresponding RT learning curves. The overall results suggest that
      short term sequential priming and long-term practice modulate RT through
      relatively separate mechanisms, even though they appear to affect a common set of
      behaviorally defined processing stages.

PMID- 12812285
TI  - Combined perceptual or motor-related expectancies modulated by type of cue.
AB  - The interaction of two expectancies was examined. These were either two
      perceptual or two response-related expectancies. Perceptual expectancies were
      induced by combining spatial cuing with feature cuing on a trial-by-trial basis.
      Cues consisted either of two integrated parts, such as two arrows, or two
      separated pieces, such as an arrow and a word. Spatial-cuing effects were reduced
      on trials with invalid feature cues, as compared with valid ones. However, the
      interaction of spatial cuing and feature cuing was modulated by the type of cue
      used to induce expectancies. With integrated cues, spatial-cuing effects were
      reduced about twice as much as with separated cues. The same effect of type of
      cue was found in Experiment 2, although finger cuing was combined with hand
      cuing. With integrated cues, finger-cuing effects were much smaller on trials
      with invalid hand cues, as compared with valid ones. With separated cues,
      however, finger-cuing effects were additive to hand-cuing effects. The similarity
      of the results within perceptual- and motor-cuing tasks suggests that a general
      principle governs the combination of expectancies, such as that outlined in the
      framework of the proposed adjusted expectancy model.

PMID- 12812286
TI  - Influence of negatively charged interfaces on the ground and excited state
      properties of methylene blue.
AB  - Properties of the ground and excited states of methylene blue (MB) were studied
      in negatively charged vesicles, normal and reverse micelles and sodium chloride
      solutions. All these systems induce dimer formation as attested by the appearance
      of the dimer band in the absorption spectra (lamdaD approximately 600 nm). In
      reverse micelles the dimerization constant (KD) corrected for the aqueous
      pseudophase volume fraction is two-three orders of magnitude smaller than KD of
      MB in water, and it does not change when W0 is increased from 0.5 to 10.
      Differences in the fluorescence intensity as a function of dimer-monomer ratio as
      well as in the resonance light scattering spectra indicate that distinct types of
      dimers are induced in sodium dodecyl sulfate (SDS) micelles and aerosol-OT
      (sodium dioctyl sulfoxinate, AOT) reversed micelles. The properties of the
      photoinduced transient species of MB in these systems were studied by time
      resolved near infrared (NIR) emission (efficiency of singlet oxygen generation),
      by laser flash photolysis (transient spectra, yield and decay rate of triplets)
      and by thermal lensing (amount of heat deposited in the medium). The competition
      between electron transfer (dye*-dye) and energy transfer (dye*-O2) reactions was
      accessed as a function of the dimer-monomer ratio. The lower yield of electron
      transfer observed for dimers in AOT reverse micelles and intact vesicles compared
      with SDS micelles and frozen vesicles at similar dimer-monomer ratios is related
      with the different types of aggregates induced by each interface.

PMID- 12812287
TI  - Metallophthalocyanines photosensitize the breakdown of (hydro)peroxides in
      solution to yield hydroxyl or alkoxyl and peroxyl free radicals via different
      interaction pathways.
AB  - Interactions of organic peroxides (R'OOR) and hydroperoxides (R'OOH), including
      H2O2, with excited triplet and singlet state metallophthalocyanines (MPc, M = Zn,
      Al) have been studied by T-T absorption decay and fluorescence quenching. The
      ensuing photochemical processes result in decomposition of (hydro)peroxides as
      assessed by photo-EPR (electron paramagnetic resonance) and spin trapping. In
      argon-saturated apolar solutions and low MPc concentrations, alkoxyl free
      radicals (*OR) were identified as the primary products of (hydro)peroxide
      breakdown. Similarly, photosensitized decomposition of symmetric disulfides
      results in the formation of sulfur-centered radicals. In air-free aqueous
      solutions, ROOH photosensitization always gave rise to a mixture of hydroxyl and
      peroxyl radical (*OOR) adducts in varying molar ratios. At high MPc
      concentrations, both in polar and in apolar solutions, the most abundant products
      of ROOH decomposition were identified as *OOR. This indicates a change in the
      predominant interaction pathway, most likely mediated by MPc exciplexes and
      involving H-atom abstraction from ROOH by MPc-cation radicals. The prevalence of
      MPc singlet vs. triplet state interactions was confirmed by the much higher
      singlet quenching rate constants (log kq up to 9.5; vs. log kT < or = 4.5). In
      contrast to the triplet quenching, singlet quenching rates were found to depend
      on the (hydro)peroxide structure, following closely the trend of varying *OR
      yields for different substrates. Thermodynamic calculations were performed to
      correlate experimental results with models for electronic energy and charge
      transfer processes in agreement with the Marcus theory (Rhem and Weller
      approximation) and Saveant's model for a concerted dissociative electron transfer
      mechanism.

PMID- 12812288
TI  - Photocontrol of cell adhesion and proliferation by a photoinduced cationic
      polymer surface.
AB  - In this study photoinduced cation generation, based on the photochemical
      properties of malachite green (MG), was used for the surface design and in vitro
      photochemical control of cell adhesion and proliferation. The MG-derivatized
      surface was prepared by coating a photoreactive polymer as a substrate onto a
      poly(ethylene terephthalate) (PET) sheet. The photoreactive polymer was radical
      copolymer of styrene with the MG-derivatized monomer diphenyl(4
      vinylphenyl)methane leucohydroxide (degree of substitution of MG unit: 12.4
      mol%). Water contact angle measurements and X-ray photoelectron spectroscopy
      revealed high hydrophobicity and homogeneous distribution of the MG groups on the
      outermost surface of the coated film, respectively. When the coated film was
      exposed to ultraviolet light (UV) irradiation at wavelengths of 290-410 nm, a
      time-dependent color change of the film was observed from pale yellow, before
      irradiation, to green. These results indicated generation of cations on the film
      surface by photochemical cation generation of the MG groups, which was
      quantitatively characterized by force versus distance curves measurements in
      atomic force microscopic (AFM) observation using a carboxylated AFM tip. The
      seeding and culture of endothelial cells showed a marked reduction in adhesion on
      the nonirradiated coated film surface, whereas the UV-irradiated surface promoted
      cell adhesion and proliferation except for incubation in serum-free medium, which
      was similar to commercial tissue culture PET sheet. These observations may be due
      to adsorption of cell adhesive proteins, typified by fibronectin, in serum
      containing medium onto the cationized photoreactive copolymer surface by
      electrostatic interactions.

PMID- 12812289
TI  - Photochemical and photophysical properties of indoprofen.
AB  - The photophysical properties and photochemistry of indoprofen (INP) have been
      investigated. Absorption and emission spectroscopies in phosphate buffer, ethanol
      and ether show that INP photophysics is dominated by a singlet-singlet transition
      of pipi* character. INP fluoresces at room temperature, with a quantum yield
      approximately 0.04. Flash photolysis experiments together with the lack of
      phosphorescence at room temperature point to a very weak intersystem crossing.
      The photoreactivity of INP is centered on the propionic acid chain and gives rise
      to photoproducts similar to those obtained with other arylpropionic acids (ethyl,
      hydroxyethyl and acetyl derivatives). Thus, irradiation of INP in aqueous buffer
      results in photodecarboxylation and leads mainly to oxidative compounds whose
      proportions increase with increasing oxygen concentration. These data suggest a
      photoreactivity occurring from the excited singlet state.

PMID- 12812290
TI  - Dipole and oscillator strengths of chromophores in solution.
AB  - A widely published expression for dipole strengths of optical transitions is
      found to require correction. The proposed adjustment, which involves the
      refractive index of the solvent in which the strengths are measured, may lead to
      significant changes in predictions that have been based on the equation. We
      discuss a closely related issue, the vacuum dipole strength concept, in an
      empirical context. A simple mapping procedure for estimating index dependence of
      strengths is advocated as an alternative to effective field corrections. The
      technique is illustrated for chlorophyll a and bacteriochlorophyll a.

PMID- 12812291
TI  - Dipole strengths in the chlorophylls.
AB  - Measurements of dipole strengths of chlorophylls in solution are reviewed and
      correlated. The refractive index dependence is found to be expressible in a
      simple empirical fashion that does not rely on the concept of vacuum dipole
      strength. The index dependence in some respects contradicts the dependence
      expected on the basis of effective field theories.

PMID- 12812292
TI  - The thiourea group modulates the fluorescence emission decay of fluorescein
      labeled molecules.
AB  - We have investigated the spectral properties and emission characteristics of
      fluorescein-5-thiocarbamoyl-N,N'-caproate (FITC-ACA) to examine the origin of the
      complex emission decay often observed in fluorescein-labeled molecules. The
      covalent attachment of fluorescein to epsilon-amino-n-caproic acid does not
      perturb the prototropic transitions of the chromophore or the general
      fluorescence characteristics of the various prototropic forms. However, both the
      monoanion and dianion forms of FITC-ACA are quenched relative to free fluorescein
      and exhibit a complex emission decay that is described by two discrete lifetimes.
      The thiourea group that links the chromophore to the caproic acid is shown to
      modulate the emission properties of the FITC-ACA. We show that the emission decay
      can also be analyzed using the asymmetric distribution model of Alcala et al. In
      this analysis, the tauL and tauu parameters that represent the lower and upper
      lifetime limits of the distribution reflect the quenched (0 ns) and unquenched
      lifetimes, respectively. The beta parameter that describes the distribution of
      lifetimes between the two limiting states can be related to the quenching
      efficiency of the thiourea group and to the structure and dynamics of the FITC
      ACA molecule.

PMID- 12812293
TI  - Lengthening of fluorescence lifetimes in self-organized metal-organic assemblies.
AB  - Resonance energy transfer from tris(2,2'-bipyridyl)ruthenium (II)
      ([Ru(bpy)3](2+)) to nile blue A is demonstrated in aqueous solution in the
      presence of sodium dodecyl sulfate (SDS). At SDS concentrations below the
      critical micelle concentration, aggregates that permit energy transfer between
      these dyes at optically dilute (10 microM) concentrations with nearly 100%
      efficiency are formed. The disparity between the lifetimes of the donor and
      acceptor results in the lengthening of the photoluminescence lifetime of the
      sensitized emission observed from nile blue A. Time-resolved luminescence
      measurements confirm that the long-lived components of the emission originate
      from sensitized acceptor emission.

PMID- 12812294
TI  - Simultaneous time resolution of the emission spectra of fluorescent proteins and
      zooxanthellar chlorophyll in reef-building corals.
AB  - Light is absorbed by photosynthetic algal symbionts (i.e. zooxanthellae) and by
      chromophoric fluorescent proteins (FP) in reef-building coral tissue. We used a
      streak-camera spectrograph equipped with a pulsed, blue laser diode (50 ps, 405
      nm) to simultaneously resolve the fluorescence spectra and kinetics for both the
      FP and the zooxanthellae. Shallow water (<9 m)-dwelling Acropora spp. and
      Plesiastrea versipora specimens were collected from Okinawa, Japan, and Sydney,
      Australia, respectively. The main FP emitted light in the blue, blue-green and
      green emission regions with each species exhibiting distinct color morphs and
      spectra. All corals showed rapidly decaying species and reciprocal rises in
      greener emission components indicating Forster resonance energy transfer (FRET)
      between FP populations. The energy transfer modes were around 250 ps, and the
      main decay modes of the acceptor FP were typically 1900-2800 ps. All
      zooxanthellae emitted similar spectra and kinetics with peak emission
      (approximately 683 nm) mainly from photosystem II (PSII) chlorophyll (chl) a.
      Compared with the FP, the PSII emission exhibited similar rise times but much
      faster decay times, typically around 640-760 ps. The fluorescence kinetics and
      excitation versus emission mapping indicated that the FP emission played only a
      minor role, if any, in chl excitation. We thus suggest the FP could only
      indirectly act to absorb, screen and scatter light to protect PSII and underlying
      and surrounding animal tissue from excess visible and UV light. We conclude that
      our time-resolved spectral analysis and simulation revealed new FP emission
      components that would not be easily resolved at steady state because of their
      relatively rapid decays due to efficient FRET. We believe the methods show
      promise for future studies of coral bleaching and for potentially identifying FP
      species for use as genetic markers and FRET partners, like the related green FP
      from Aequorea spp.

PMID- 12812295
TI  - Fluorescence spectral imaging of dihydroxyacetone on skin in vivo.
AB  - Dihydroxyacetone (DHA) has been proposed as a potential alternative to dansyl
      chloride for use as a fluorescence marker on skin to assess stratum corneum
      turnover time in vivo. However, the fluorescence from DHA on skin has not been
      adequately studied. To address this void, a noninvasive, noncontact spectral
      imaging system is used to characterize the fluorescence spectrum of DHA on skin
      in vivo and to determine the optimal wavelengths over which to collect the DHA
      signal that minimizes the contributions from skin autofluorescence. The DHA-skin
      fluorescence signal dominates the 580-680 nm region of the visible spectrum when
      excited with ultraviolet radiation in the 320-400 nm wavelength region (UVA). An
      explanation of the time-dependent spectral features is proposed in terms of DHA
      polymerization and binding to skin.

PMID- 12812296
TI  - Influence of UVB, UVA and UVA1 irradiation on histamine release from human
      basophils and mast cells in vitro in the presence and absence of antioxidants.
AB  - UV irradiation is widely used for the treatment of atopic eczema. In recent
      years, UVA1 phototherapy has gained increasing attention. This study analyzed the
      influence of different UV wavelengths--especially UVA1--on histamine release from
      human basophils and mast cells. The modulation of this parameter might be
      responsible for some of the therapeutic effects of UV irradiation. Enriched human
      basophils and human mast cells (HMC1 cell line) were irradiated with increasing
      doses of UVB, UVA and UVA1 in vitro. After irradiation, different stimulants were
      added to induce histamine release. In additional experiments, basophils were
      preincubated with superoxide dismutase, ascorbate or trolox to study the role of
      antioxidants in the modulation of histamine release after UV irradiation. UVA and
      UVA1 significantly inhibited histamine release from basophils and mast cells. UVB
      only had an inhibitory effect on mast cells. Preincubation with superoxide
      dismutase and ascorbate did not influence the inhibitory effect of UVA1 on
      basophil histamine release, whereas trolox decreased significantly the histamine
      release from nonirradiated basophils.

PMID- 12812297
TI  - Study of the interaction between triplet riboflavin and the alpha-, betaH- and
      betaL-crystallins of the eye lens.
AB  - Time-resolved photolysis studies of riboflavin (RF) were carried out in the
      presence and absence of alpha-, betaH- and betaL-crystallins of bovine eye lens.
      The transient absorption spectra, recorded 5 micros after the laser pulse, reveal
      the presence of the absorption band (625-675 nm) of the RF neutral triplet state
      (tau = 42 micros) accompanied by the appearance of a long-lived absorption (tau =
      320 micros) in the 500-600 nm region due to the formation of the semireduced RF
      radical. The RF excited state is quenched by the crystallin proteins through a
      mechanism that involves electron transfer from the proteins to the flavin, as
      shown by the decrease of the triplet RF band with the concomitant increase of the
      band of its semireduced form. Tryptophan loss on RF-sensitized photooxidation of
      the crystallins when irradiated with monochromatic visible light (450 nm) in a 5%
      oxygen atmosphere was studied. A direct correlation was found between the triplet
      RF quenching rate constants by the different crystallin fractions and the
      decomposition rate constants for the exposed and partially buried tryptophans in
      the proteins. The RF-sensitized photooxidation of the crystallins is accompanied
      by the decrease of the low molecular weight constituents giving rise to its
      multimeric forms. A direct correlation was observed between the initial rate of
      decrease of the low molecular weight bands corresponding to the irradiated alpha
      , betaH- and betaL-crystallins and the quenching constant values of triplet RF by
      the different crystallins. The correlations found in this study confirm the
      importance of the Type-I photosensitizing mechanism of the crystallins, when RF
      acts as a sensitizer at low oxygen concentration, as can occur in the eye lens.

PMID- 12812298
TI  - Morphological changes in blood vessels produced by hyperosmotic agents and
      measured by optical coherence tomography.
AB  - Optical tissue clearing by hyperosmotic chemical agents significantly increases
      light depth penetration in skin and may improve light-based therapeutics such as
      laser treatment of cutaneous vascular lesions. A feasibility study was conducted
      to evaluate the potential role of optical clearing by glycerol in laser treatment
      of cutaneous vessels. Optical imaging was performed to investigate the
      morphological effects of glycerol on blood vessels of skin. Blood vessels were
      imaged using Doppler optical coherence tomography in in vivo hamster skin treated
      with glycerol. Images were obtained from the subdermal side to assess
      morphological changes in the blood vessels caused by glycerol and from the
      epidermal side to assess enhanced Doppler imaging of blood vessels. Application
      of glycerol to the subdermis resulted in venule stasis and for prolonged
      treatment times, arteriole stasis. In cases where flow remained in arterioles, an
      improved Doppler signal was detected from blood vessels when imaging
      transepidermally compared with the native condition. Intensity images indicated
      changes in blood optical properties and improved contrast of skin cross sections
      after glycerol application. The observed optical and morphological effects were
      reversed upon hydration of the skin with phosphate-buffered saline. The
      combination of increased depth of light penetration and the temporary slowing or
      cessation of flow in blood vessels could mean improved laser treatment of
      vessels.

PMID- 12812299
TI  - Microanatomical and biochemical origins of normal and precancerous cervical
      autofluorescence using laser-scanning fluorescence confocal microscopy.
AB  - Clinical studies have shown that in vivo fluorescence spectroscopy can improve
      the diagnosis of cervical precancer. Recent work suggests that epithelial
      fluorescence increases, whereas stromal fluorescence decreases, with precancer.
      However, the microanatomic and biochemical sources of fluorescence in living
      cervical tissue have not yet been established. This study aims to characterize
      the origins of living normal and precancerous cervical fluorescence at
      microscopic levels using laser-scanning fluorescence confocal microscopy. Ten
      pairs of colposcopically normal and abnormal biopsies were obtained; transverse,
      200 microm thick, short-term tissue cultures were prepared and imaged when viable
      with UV (351-364 nm) and 488 nm excitation before and after addition of the vital
      dye, Mitotracker Orange. In normal epithelium basal epithelial cells showed
      cytoplasmic fluorescence; parabasal, intermediate and superficial cells showed
      fluorescence only at the periphery of the cell. In low-grade precancers
      cytoplasmic fluorescence was visible in the bottom one-third of the epithelium;
      in high-grade precancers cytoplasmic fluorescence was visible throughout the
      lower two-thirds of the epithelium. Cytoplasmic fluorescence was colocalized with
      the MitoTracker probe and is attributed to mitochondrial reduced form of
      nicotinamide adenine dinucleotide at UV excitation and mitochondrial flavin
      adenine dinucleotide at 488 nm excitation. Stromal fluorescence originated from
      matrix fibers; with the development of precancer the density and fluorescence
      intensity of matrix fibers decrease. Autofluorescence properties of precancerous
      cervix reflect an increased number of metabolically active mitochondria in
      epithelial cells and a reduced stromal fluorescence, which can be an indicator
      for altered communication between precancerous epithelium and stroma. These
      changes can explain differences in in vivo fluorescence spectra of normal and
      precancerous cervical tissue.

PMID- 12812300
TI  - Photodynamic inactivation of the dermatophyte Trichophyton rubrum.
AB  - Dermatophytes are fungi that can cause infections (known as tinea) of the skin,
      hair and nails because of their ability to use keratin. Superficial mycoses are
      probably the most prevalent of infectious diseases worldwide. One of the most
      distinct limitations of the current therapeutic options is the recurrence of the
      infection and duration of treatment. The present study shows that Trichophyton
      rubrum in suspension culture is susceptible to photodynamic treatment (PDT), a
      completely new application in this area. T. rubrum could be effectively killed
      with the use of the light-activated porphyrins deuteroporphyrin monomethylester
      (DP mme) and 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine
      trichloride (Sylsens B). The photodynamic efficacy was compared with that of some
      other photosensitizers that are well known in the field of PDT: the porphyrins
      deuteroporphyrin and hematoporphyrin, the drug Photofrin and several
      phthalocyanines. It was demonstrated that with the use of broadband white light,
      the phthalocyanines and Photofrin displayed a fungistatic effect for about 1
      week, whereas all the porphyrins caused photodynamic killing of the dermatophyte.
      Sylsens B was the most effective sensitizer and showed no dark toxicity;
      therefore, in an appropriate formulation, it could be a promising candidate for
      the treatment of various forms of tinea. For Sylsens B and DP mme, which
      displayed the best results, a concentration-dependent uptake by T. rubrum was
      established.

PMID- 12812301
TI  - Structure-activity relationship of new octaethylporphyrin-based benzochlorins as
      photosensitizers for photodynamic therapy.
AB  - An in vitro and in vivo structure-activity relationship study was carried out on
      a series of benzochlorins with variable lipophilicity. The structural features
      evaluated in this study include the length of the alkyl or fluoroalkyl groups
      attached to the six-member exocyclic ring either by an ether or by a carbon
      carbon bond. In preliminary in vitro (radiation-induced fibrosarcoma [RIF] cells)
      and in vivo screening (C3H mice, bearing RIF tumors), all Zn (II) benzochlorins
      were found to be effective. However, benzochlorins bearing alkyl groups with
      carbon-carbon bonds showed enhanced efficacy compared with the related alkyl
      ether analogs. A comparative intracellular localization study of the newly
      synthesized benzochlorins with Rhodamine-123 indicated that the effective
      photosensitizers localize in mitochondria, and a displacement study with PK11195
      showed their partial affinity for the peripheral benzodiazepine receptor (PBR).
      Interestingly, compared with the Zn(II) benzochlorin that was found to be quite
      effective in vivo, the corresponding free-base analog produced less
      photosensitizing activity and was found to localize in lysosomes. A comparative
      study with dansyl-proline confirmed the binding of the effective benzochlorins to
      Site II of human serum albumin (HSA). However, no direct correlation was observed
      between the binding constant values (to HSA or to PBR) of benzochlorins and their
      photosensitizing ability.

PMID- 12812302
TI  - Photosensitized structural modifications of the lens protein alpha-crystallin: do
      all modifications impair chaperone-like activity?
AB  - Among chaperone-like functioning proteins, the lens alpha-crystallins are of
      particular interest because they are not renewed, and even minor alterations can
      hurt their function of maintaining the proper refractive index and avoiding
      cataract formation in the lens. Several reports have suggested the occurrence of
      remarkable structural modifications in lens proteins in the presence of
      endogenous and exogenous sensitizers upon exposure to light. In particular, it
      has been shown in vitro that hypericin, the active ingredient of Hypericum, can
      bind to and, in the presence of light, cause the photopolymerization of alpha
      crystallin. On the basis of these results it has also been suggested that a
      subsequent significant impairment of the protein function can occur. Using
      absorption and emission spectroscopic techniques, as well as circular dichroism,
      we have studied the structural modifications of alpha-crystallin resulting from
      its interaction with hypericin after irradiation with visible light. To
      investigate the chaperone-like function of alpha-crystallin, the heat-induced
      aggregation kinetics of another lens protein, betaLow-crystallin, was monitored
      by measuring the apparent absorption due to scattering at 360 nm as a function of
      time, and no apparent damage to its functional role was observed. Spectroscopic
      results, on the contrary, show a prominent reduction in both tryptophan and
      hypericin fluorescence emission intensity after light irradiation, suggesting an
      alteration in the tryptophan microenvironment and a high degree of packing of the
      chromophore due to photoinduced modification of the molecular framework. Control
      experiments on alpha-crystallin structurally modified by light in the presence of
      hypericin indicated that the protein still retains its ability to chaperone both
      lens crystallins and insulin.

PMID- 12812303
TI  - Effect of alkali metal ions on photochromic behavior of bisviologen-incorporated
      oligo-oxyethylene units.
AB  - Two bisviologen derivatives, 1,11-bis(N-propyl-4,4'-bipyridinium)-3,6,9
      trioxaundecane tetrakis-(hexafluorophosphate) (1) and 1,8-bis(N-propyl-4,4'
      bipyridinium)-3,6-dioxaoctane tetrakis-(hexafluorophosphate) (2), each
      incorporating trioxaundecane and dioxaoctane groups between two viologen units,
      respectively, were prepared so that their photochromic behavior in the absence
      and the presence of alkali metal ions in a thin polymer film could be
      investigated. Photoirradiation of the films containing 1 and 2 caused color
      changes from pale yellow to blue, associated with the photoinduced reduction of
      the viologen units from the dication to the radical cation. The addition of
      alkali metal ions, especially, K+ and Na+, caused change in the spectra of the
      photoreduced viologen radical cation for 1 and 2, respectively, because of the
      increase in the fractional amplitude for the dimer component of the radical
      cation rather than the monomer one. This may be related to the guest-induced
      conformational change of 1 and 2, in which the alkali metal ion is surrounded by
      the oligo-oxyethylene unit of 1 and 2. The regulation in photochromic properties
      of viologen derivatives can be achieved by addition of alkali metal ions.

PMID- 12812304
TI  - Tuberculosis of the pituitary and sellar region.

PMID- 12812305
TI  - Pituitary tuberculoma: an unusual lesion of sellar region.
AB  - Pituitary tuberculomas are extremely rare lesions, with only few cases described
      in the literature, usually mistaken as pituitary tumors. Its heterogeneous
      clinical and imaging profile preclude preoperative diagnosis which ultimately
      relies on the histopathological examination. We describe a 46 years old woman who
      presented with an episode of confusion and hypopituitarism with no evidence of
      systemic tuberculosis. Computed tomography (CT) showed a central calcified and
      enhancing sellar mass. Magnetic resonance imaging (MRI) showed a sellar mass with
      suprasellar extension and associated optic chiasm compression. She was submitted
      a craniotomy for biopsy and resection. A caseous material was found at the center
      of the lesion involved by a thick wall. Due to the wall adherence to the optic
      chiasm and the inflammatory aspects of the lesion, subtotal removal was achieved
      and the patient followed on anti-tuberculous and hormonal replacement therapy.
      Sellar tuberculomas should be considered in the differential diagnosis of sellar
      tumors in order to offer appropriate treatment.

PMID- 12812306
TI  - Pituitary stalk tuberculoma.
AB  - Pituitary tuberculomas are exceptionally rare. Even with no evidence of systemic
      tuberculosis, it is important to recognize these lesions in the differential
      diagnosis of the intrasuprasellar tumors because they are curable. At present, in
      developed countries the frequency of intracranial tuberculomas of nervous system
      tumors is around 0.5-4%, whereas in under developed countries is 15-30%. It
      mainly affects children and young adults. In some cases, an accurate diagnosis
      may lead to an efficient medical therapy on the basis of biological, hormonal and
      imaging scans examinations. The case we studied shows the difficulties
      encountered in the diagnosis of a thickened stalk having normal pituitary image.
      It is to be highlighted the usage of the Polymerase Chain Reaction (PCR)
      technique.

PMID- 12812307
TI  - Adrenocorticotrope deficiency with clinical evidence for late onset in combined
      pituitary hormone deficiency caused by a homozygous 301-302delAG mutation of the
      PROP1 gene.
AB  - Combined pituitary hormone deficiency (CPHD) can be caused by mutation of the
      pituitary transcription factors POU1F1 or PROP1. More recently mutations in the
      HESX1, the LHX3 and LHX4 transcription factor genes have also been described as a
      cause in patients with CPHD. In most patients the disorder is characterized by an
      impaired production of GH, TSH, PRL and gonadotropins. In some cases of CPHD
      adrenocorticotropin deficiency is also present. We report the progressive CPHD
      and its molecular etiology in a woman with CPHD presenting with first symptoms of
      ACTH/cortisol deficiency at the age of 48 years. The 49 year old patient's
      initial symptoms were growth retardation at the age of 2 years and symptoms of
      hypothyroidism at the age of 5 years. The patient never entered puberty
      spontaneously. No familial history of delayed puberty, growth retardation or
      other symptoms of CPHD were present. At the age of 48 years the patient presented
      with the first symptoms of hypocortisolism such as recurring hypoglycaemias and
      hyponatriaemia with coma. Cortisol, ACTH, TSH, fT3, fT4 and GH as well as LH, FSH
      and PRL were measured in basal conditions. GH, cortisol and ACTH were also
      measured in response to an Insulin Tolerance Test. Molecular analysis was
      performed by PCR amplification and sequencing of exon 1-3 of the PROP1 gene. The
      patient had insufficiencies of TSH, LH, FSH and GH. PRL was normal. Serum
      cortisol was low and basal ACTH was normal. However, there were no responses of
      cortisol, ACTH and GH to hypoglycaemia. Magnetic resonance imaging showed a
      hypoplastic anterior pituitary lobe. Direct sequencing revealed a homozygous 2
      base-pair deletion 301-302delAG in exon 2 of the PROP1 gene. This case suggests
      that in patients with CPHD ACTH producing cells may be involved at a rather late
      age.

PMID- 12812308
TI  - Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary
      adenoma.
AB  - Stereotactic radiosurgery is being used with increased frequency in the treatment
      of residual or recurrent pituitary adenomas. The major risk associated with
      radiosurgical treatment of residual or recurrent pituitary tumor adjacent to
      normal functional pituitary gland is radiation of the pituitary, which frequently
      leads to the development of hypopituitarism. The authors describe a technique of
      pituitary transposition to reduce the radiation dose to the normal pituitary
      gland in cases of planned radiosurgical treatment of residual pituitary adenoma
      within the cavernous sinus. A sellar exploration for tumor resection is
      performed, the pituitary gland is transposed from the region of the cavernous
      sinus, and a fat and fascia graft is interposed between the normal pituitary
      gland and the residual tumor in the cavernous sinus. The residual tumor may then
      be treated with stereotactic radiosurgery. The increased distance between the
      normal pituitary gland and the residual tumor facilitates treatment of the tumor
      with radiosurgery and reduces the radiation to the normal pituitary gland. An
      illustrative case of a young female with recurrent acromegaly and a pituitary
      adenoma invading the cavernous sinus is described.

PMID- 12812309
TI  - Radiation therapy for Cushing's disease: a review.
AB  - Because patients with Cushing's disease have an increased morbidity and an age
      corrected mortality, treatment is generally started as soon as possible. The goal
      of treatment in these patients is to induce remission. Although a variety of
      treatments are available, pituitary radiation is a good option for aggressive
      Cushing's disease that fails to respond to surgery, disease that invades the
      cavernous sinus, and disease that relapses following an initial remission.
      Conventional radiation therapy, stereotactic radiosurgery, fractionated
      stereotactic radiation therapy, and brachytherapy with Yttrium-90 (Y 90) and Gold
      198 (Au 198) have been used successfully to treat ACTH-secreting pituitary
      adenomas in specialized centers. Conventional radiation therapy is the most
      frequently used method of radiation therapy for Cushing's disease. Stereotactic
      radiosurgery may be used as an alternative in patients with adenomas that are
      smaller than 30 mm and located at least 3 to 5 mm from the optic chiasm.
      Fractionated stereotactic radiation therapy is an alternative to radiosurgery
      while interstitial pituitary irradiation is an alternative to surgical resection
      in invasive tumors. Hypopituitarism is the most common side effect of pituitary
      irradiation. This article will review the role of radiation in the primary and
      secondary treatment in patients with Cushing's disease caused by pituitary
      adenomas.

PMID- 12812310
TI  - Roles of insulin-like growth factor-I and growth hormone in mediating insulin
      resistance in acromegaly.
AB  - Most patients with acromegaly have some degree of insulin resistance. The
      principal mediator of insulin resistance in acromegaly is hypersecretion of
      growth hormone. Growth hormone acts at several levels to block insulin actions
      including inhibiting phosphorylation of the insulin receptor and one of its
      principal signaling molecules IRS-1 in response to insulin administration. This
      leads to reduced sensitivity to insulin in the periphery in stimulating
      peripheral glucose uptake and to increased resistance to insulin's ability to
      suppress gluconeogenesis. Furthermore growth hormone excess leads to mobilization
      of free fatty acids which inhibit insulin stimulated glucose oxidation by acting
      as a competitive energy source thus leading to further worsening of insulin
      resistance. These abnormalities can be overcome by administering agents which
      either lower growth hormone secretion or block growth hormone action. The role of
      elevated IGF-I in acromegaly in mediating insulin resistance is more difficult to
      analyze. Indirect inferences from the data that are available suggest that IGF-I
      is acting to enhance insulin sensitivity and partially counteracting the insulin
      antagonistic effects of growth hormone. In a recent study administration of IGF-I
      to acromegalics was shown to improve insulin sensitivity over and above the level
      that could be achieved by simply blocking growth hormone action. Therefore it
      appears that the net effect of IGF-I is to counterbalance some of the effects of
      growth hormone hypersecretion on insulin resistance.

PMID- 12812312
TI  - Morphology of necrosis and repair after transcoronary ethanol ablation of septal
      hypertrophy.
AB  - The transcoronary ethanol ablation of septum hypertrophy (TASH) results in a
      necrosis of the myocardium. In contrast to the ischemically induced necrosis,
      there is not any phagocytosis caused by leukocytes and macrophages, nor does
      transformation into granulation tissue occur. Even six months after the
      application of ethanol, the myofibrils can be identified as "ghost cells"
      surrounded by a web of collagen fibers. This special forming of a scar, unknown
      to this day, is documented by 13 patients who died between 25 minutes and two
      years after ethanol-induced ablation of the hypertrophic septum in hypertrophic
      obstructive cardiomyopathiy (HOCM).

PMID- 12812313
TI  - Revascularization of myocardial scar tissue following prostaglandin E1-therapy in
      patients with ischemic heart disease.
AB  - Prostaglandin E1 (PGE-1) treatment has proved to stimulate angiogenesis in vital
      non-infarcted myocardium of patients with ischemic cardiomyopathy (ICMP). We
      investigated infarcted myocardial tissue for a possible angiogenic response to
      PGE-1. Neovascularization was investigated in infarcted areas of 12 hearts
      explanted from patients with ICMP who had been treated with PGE-1 before heart
      transplantation (HTX). In transmural sections containing myocardial scar tissue,
      CD34 and VEGF were immunohistochemically quantified to estimate capillary density
      and the extent of angiogenesis. To investigate a possible effect of PGE-1 on
      collagen turnover, the collagen content was determined in myocardial scar tissue
      by assessing the intensity of the area positively stained with sirius red. PGE-1
      treated patients had significantly more CD34- and VEGF-positive cells in
      infarcted areas, and showed a significant reduction in collagen content as
      compared with the non-PGE-1 group (CD34: 120.3 +/- 6.1 vs. 47.7 +/- 6.1 capillary
      profiles/mm2; VEGF: 52.8 +/- 5.6 vs. 24.0 +/- 4.8 capillary profiles/mm2, and
      collagen content: 2.18 +/- 0.4 eU vs. 3.59 +/- 0.38 eU). Our data demonstrate
      that PGE-1 stimulates angiogenesis by upregulating VEGF expression, and reduces
      fibrosis in cardiac scar tissue of ischemic origin. The induction of therapeutic
      angiogenesis in vital and at sites of putative dead myocardial scar tissue, along
      with the hemodynamic improvement in patients with severe ICMP, might explain the
      favorable clinical outcome in PGE-1-treated patients before HTX.

PMID- 12812311
TI  - Current status and future opportunities for controlling acromegaly.
AB  - Growth-hormone (GH) secreting adenomas, including acromegaly, account for
      approximately one-sixth of all pituitary adenomas and are associated with
      mortality rates at least twice that of the general population. The ultimate goal
      of therapy for acromegaly is normalization of morbidity and mortality rates
      achieved through removal or reduction of the tumor mass and normalization of
      insulin-like growth factor I (IGF-I) levels. Previously published efficacy
      results of current treatment modalities (surgery, conventional radiation, and
      medical therapy with dopamine agonists and somatostatin analogs) are often
      difficult to compare because of the different criteria used to define cure (some
      of which are now considered inadequate). For each of these modalities, pooled
      data from a series of acromegaly studies were reviewed for rates of IGF-I
      normalization, a currently accepted definition of cure. The results showed
      overall cure rates of approximately 10% for bromocriptine, 34% for cabergoline,
      36% for conventional radiation, 50-90% for surgery for microadenomas and less
      than 50% for macroadenomas, and 54-66% for octreotide. These cure rates based on
      IGF-I normalization are generally less than those reported for cure based solely
      on GH levels. Novel new therapies for acromegaly include the somatostatin analog,
      lanreotide, Gamma Knife radiosurgery, and pegvisomant, the first in its class of
      new GH receptor antagonists. Although it does not appear that Gamma Knife
      radiosurgery results in significantly higher cure rates or fewer complications,
      it does provide a notable improvement in delivery compared with conventional
      radiation. Early studies have reported IGF-I normalization in 48% of lanreotide
      treated patients and up to 97% of pegvisomant-treated.

PMID- 12812314
TI  - Expression of CD3 epsilon subunit in gastric parietal cells: a possible role in
      signal transduction?
AB  - CD3 antigen, formerly thought to be specific for T lymphocytes, has been found on
      gastric parietal cells in animals and humans. The common anti-CD3 antibodies
      recognize the epsilon subunit, which has a role in signal transduction. The aim
      of this study was to immunostain stomach specimens from humans and different
      animal species for CD3 antigen to determine if CD3 antigen is conserved across
      species and if CD3 antigen expression is altered in humans by use of certain
      drugs or the presence of gastritis. Gastric biopsies from 50 humans and necropsy
      sections from 13 different animals were immunostained using commercial anti CD3
      epsilon antibodies on an automated immunostainer. Sections of stomach from four
      mice lacking the gastric H+,K(+)-ATPase alpha-subunit and four control mice were
      similarly immunostained. CD3 epsilon antigen expression in cytoplasm and cell
      membranes of gastric parietal cells was graded subjectively based on the number
      of positive cells. CD3 epsilon antigen was found on gastric parietal cells in all
      but one species studied, with varying expression in membranes and cytoplasm.
      There was a trend toward a decreased frequency of CD3+ cells in biopsies from
      patients on drugs (n = 23) compared to those on no drugs (n = 27). This trend was
      most marked in patients on H2 receptor antagonists. There was no correlation
      between CD3 expression and inflammation or Helicobacter pylori (H. pylori)
      infection. There was loss of CD3 expression in parietal cells in mice lacking the
      alpha-subunit of H+,K(+)-ATPase. These findings support previous observations
      that CD3 antigen is present in gastric parietal cells, and suggest that it may
      function in signal transduction during acid secretion.

PMID- 12812315
TI  - A method for the detection of eosinophilic granulocytes in colonoscopic biopsies
      from IBD patients.
AB  - Eosinophilic granulocytes were found to be autofluorescent when Giemsa-stained
      sections were stimulated with indirect light fluorescence (ILF). The frequency of
      autofluorescent eosinophils was assessed in areas with diffuse and focal
      inflammation in 76 consecutive colonoscopic biopsies from patients with
      inflammatory bowel disease (IBD), Crohn's disease (CD = 32), ulcerative colitis
      (UC = 30), and collagenous colitis (CC = 7). All IBD cases had moderate to severe
      pancolitis. In areas with diffuse inflammation, severe eosinophilia was recorded
      in 39.6% or in 38 of 96 high power fields investigated in patients affected by
      CD, and in 3.3% or in 3 of 90 high power fields examined in patients with UC. In
      areas with focal inflammation, the mean percentage of eosinophils in CD was 57%
      (range 44-70%), and 9% in UC (range 6-26%). No focal inflammation was present in
      CC. In the submucosa of some CD patients, a large number of autofluorescent
      eosinophils and many autofluorescent cell-free granules were seen. It was
      inferred that these autofluorescent granules had been released from eosinophils,
      and that the eosinophilic granulocytes from which these granules had originated
      were no longer discernible. Focal eosinophilic mucosal infiltration in CD is more
      common than epithelioid cell granulomas, and emerges as an important parameter in
      the histologic differential diagnosis between colonic CD and UC.

PMID- 12812316
TI  - Galectin-3 expression in normal, hyperplastic, and neoplastic endometrial
      tissues.
AB  - This study evaluated the expression of galectin-3 in 101 curettage specimens from
      normal, hyperplastic, and neoplastic endometrial tissues using
      immunohistochemistry. The histologic diagnoses were as follows: normal
      proliferative (n = 8) and secretory (n = 4) phase, simple hyperplasia (SH, n =
      16), complex hyperplasia without atypia (CH, n = 11), atypical hyperplasia (AH, n
      = 13), endometrioid adenocarcinoma (EC, n = 35), serous papillary carcinoma (SPC,
      n = 10), and clear cell carcinoma (CC, n = 4). Immunostaining was scored with
      regard to the approximate percentage of positive tumor cells and relative
      staining intensity. The scores of immunostaining increased significantly from NE,
      SH, CH, and AH to the adenocarcinomas (ANOVA, p < 0.0001). Subsequently, three
      significantly different levels of galectin-3 expression were found (Newman-Keuls
      multiple comparison test). These consisted of (a) NE, SH, and CH, (b) AH and EC,
      and (c) SPC and CC. Galectin-3 expression increased with tumor grade (ANOVA, p =
      0.0026). The scores of FIGO stages I to III did not differ significantly (ANOVA,
      p = 0.1687). Enhanced nuclear galectin-3 expression was noted in carcinomas,
      immunostaining of stromal cells decreased in the latter. This study shows that
      galectin-3 expression increases from normal and hyperplastic to atypical
      hyperplastic and cancerous states of endometrial tissues, and provides further
      evidence of a relationship between AH and EC.

PMID- 12812317
TI  - Marked clinical and histologic improvement in a patient with type-1 Gaucher's
      disease following long-term glucocerebroside substitution. A case report and
      review of current diagnosis and management.
AB  - Type-1 Gaucher's disease represents the most common lysosomal storage disorder.
      With the introduction of enzyme replacement therapy, many of the clinical
      manifestations can be controlled. The functional deficiency of the lysosomal beta
      glucocerebrosidase leads to deposition of glycosylceramide in the liver, spleen,
      and bone marrow. We report the clinical and pathologic presentation of a patient
      with a florid type-1 Gaucher's disease who received long-term enzyme replacement
      therapy, which led to marked clinical improvement. A repeat liver biopsy
      performed at the time of a cholecystectomy several years after initiation of
      enzyme replacement therapy revealed complete resolution of Gaucher cells.

PMID- 12812320
TI  - Current and future trends in medical rehabilitation.

PMID- 12812318
TI  - Morphologic changes and altered gene expression in an epithelioid
      hemangioendothelioma during a ten-year course of disease.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular
      neoplasm with unpredictable prognosis. We report on a patient suffering from a
      vascular neoplasm with primary manifestation in the skeleton and subsequent
      development of lesions of EHE in the spleen, liver and lung. Based on the
      assumption that involvement of visceral organs was due to metastatic spread,
      changes in clinical behavior, morphology, and proliferation index suggest
      malignant progression of the tumor. Analyzing the expression of genes known to be
      involved in the pathogenesis of vascular tumors, we found that the appearance of
      less differentiated tumor was paralleled by an accumulation of TP53 and murine
      double minute-2 (MDM-2) protein, decreased caveolin-1 (CAV-1) expression, and
      increased vascular endothelial growth factor (VEGF) expression. Mutations of the
      von-Hippel-Lindau-tumor-suppressor-gene (VHL) were excluded as mechanism of VEGF
      upregulation. Therefore, we propose that the expression of TP53, MDM-2, CAV-1 and
      VEGF as a marker of biologic behavior be verified in a larger case study of EHE.

PMID- 12812319
TI  - Retrobulbar cellular schwannoma. Two cases report and review of the literature.
AB  - Cellular schwannoma is a variant of classical schwannoma that is characterized by
      high cellularity. As it is accompanied by mitotic figures, it is easily mistaken
      for a malignant neoplasm. However, hyalinized thick-walled blood vessels, an
      alternating growth pattern of spindle-shaped neoplastic cells, and even Verocay
      bodies can be found. It is most commonly seen in the paravertebral area,
      particularly in the mediastinum and retroperitoneum. Retrobulbar cellular
      schwannoma is uncommon, and only one case has been reported to date. In this
      study, we report two additional cases of retrobulbar cellular schwannoma that
      recurred two years after surgery. We suggest that the patient be given an
      aggressive postoperative treatment because a successful, complete excision cannot
      be guaranteed at such an anatomic site.

PMID- 12812321
TI  - ISPO policy with regard to consumers as users of prostheses and orthoses.

PMID- 12812322
TI  - Vocational reintegration after a lower limb amputation: a qualitative study.
AB  - The objectives of this study were to describe the process of job reintegration,
      to obtain more detailed information about workplace adjustments, and to assess
      the positive and negative experiences of amputees (in the Netherlands) who
      returned to paid work after their lower limb amputation. The study had a
      retrospective design with semi-structured interviews. The authors used a
      qualitative methodology to obtain detailed information on the reintegration
      process. Thirty-two (32) subjects participated with a mean age of 42.6 years. The
      mean time between amputation and return to work was nearly one year (11.5
      months). The most common reasons for delay in return to work were stump problems
      and problems in wound healing. Fifty percent (50%) of the amputees got different
      work tasks or another job than before amputation, mainly because of physical
      restrictions caused by the amputation. The most important motives of the amputees
      for job reintegration were work as a form of day spending (69%) and social
      contacts at the workplace (66%). Bad support of the implementing body which takes
      care of job reintegration and employer (34%) were the most mentioned obstacle to
      job reintegration. Vocational workers should be regular members in the
      rehabilitation teams for amputees.

PMID- 12812323
TI  - Social integration of juvenile amputees: comparison with a general population.
AB  - The objective was to assess the social integration of juvenile amputees according
      to marital status, schooling and occupation, and to compare it with the
      population of Asturias, Spain. A retrospective study was carried out of the
      juvenile amputees registered from 1976 to 1999 at the Prosthetics Unit of the
      Asturias Central Hospital (n=281 amputees). The proportion of single women
      amongst the amputees was greater than in the population of Asturias (p<0.05).
      Amongst the male amputees, relative to the general population, there was a larger
      proportion of the group with primary studies (p<0.001) and a smaller proportion
      with secondary studies (p<0.001). At the higher level (university) there were no
      differences, either in men or in women. As regards occupation, amongst the
      amputees a larger number was found who were retired or unemployed (p<0.05 and
      p<0.001). In conclusion, juvenile amputees do not show differences compared to
      the general population with regard to their attendance at a higher or university
      level of education. However, if their social integration is considered through
      occupation, male amputees show a greater proportion of unemployment, which is a
      clear reflection of their handicap.

PMID- 12812324
TI  - The influence of prosthetic foot alignment on trans-tibial amputee gait.
AB  - An optimally aligned prosthesis, as accomplished by the subjective judgment of
      the prosthetist, guarantees the best quality of gait. Yet, amputees can adapt to
      a large variety of geometrical configurations of the prosthetic components.
      Different external rotation angles of the foot in trans-tibial (TT) prostheses
      were investigated. The study tried to identify (a) the relationship between foot
      angle and other gait parameters and (b) the compensating pattern of the amputees
      to excessive external rotation of the foot. Eight (8) TT amputees, fitted with an
      identical type of prosthesis, were investigated during ambulation. The prosthetic
      foot was externally rotated as follows: optimal angle (10.94 x degrees +/- 5.21
      degrees), optimal angle plus another 18 degrees, and optimal angle plus another
      36 degrees. Analysis of gait was performed with the aid of an electronic walkway.
      Speed of gait, stance and swing time, and foot angle were monitored in 4 runs for
      each of the three foot angles. Speed of gait remained almost constant in the
      three tests. Stance and swing time, as well as step length, significantly changed
      when 36 degrees were added to the optimal foot angle. This foot position
      significantly influenced inter-legs time difference and symmetry between the
      legs. During ambulation, prosthetic foot external rotation was decreased by
      internal rotation of the limb at the hip joint level. It is concluded that TT
      amputees can maintain an efficient speed of gait even when the prosthetic foot is
      malpositioned in excessive external rotation. Although such a malalignment
      significantly influences other gait parameters during walking, amputees are able
      to adapt themselves by internal rotation of the hip joint in the amputated leg.

PMID- 12812325
TI  - An evaluation of the effectiveness of the patellar tendon bar in the trans-tibial
      patellar-tendon-bearing prosthesis socket.
AB  - The aim of this study is to determine the relationship between varying depths of
      the patellar tendon bar in trans-tibial prosthesis sockets and the pressures
      exerted by other regions within the socket, such as the tibial crest, medial and
      lateral tibial condyles, lateral femoral condyle and the distal tibial end. Five
      (5) patients selected from a population of trans-tibial amputees in Singapore.
      Patellar-tendon-bearing (PTB) sockets were made for them. Polypropylene spacers 2
      mm thick were used to simulate the increasing depths of the patellar tendon bar.
      P-Scan pressure transducers were inserted into the sockets to measure the
      pressures exerted by the socket and the data collected were analysed
      statistically to see if there was a relationship between varying PTB depths and
      pressures exerted from selected parts of the socket.

PMID- 12812326
TI  - Walking and running inter-limb asymmetry for Paralympic trans-femoral amputees, a
      biomechanical analysis.
AB  - The aim of this project was to further the research and understanding of the
      trans-femoral amputee's ability to walk and run by comparing the changes in
      walking and running inter-limb asymmetry. An objective biomechanical analysis was
      conducted on four male transfemoral amputees, all members of the Australian
      Paralympic training squad for the 1996 Atlanta Paralympic Games. The data was
      collected in the biomechanics laboratories at Queensland University of Technology
      and the Australian Institute of Sport. The main outcomes measure a synchronised
      3D kinematic (200 Hz), kinetic (600 Hz) and temporal analysis of walking at self
      selected (1.1-1.3 m/s), and at maximal running speed (2.5-4.3 m/s). The walking
      and running biomechanical data was summarised into 27 indices of symmetry. The
      results showed that for all subjects the inter-limb asymmetry was significantly
      different at running speed, when compared to the walking speed. Using indices of
      symmetry 79% of the kinematic, 67% of the kinetic, and 67% of the temporal
      measurements identified better inter-limb asymmetry when the subjects walked,
      compared to running. This study objectively identified that when Paralympic level
      amputees ran on their standard running prosthesis, the inter-limb asymmetry was
      exacerbated.

PMID- 12812327
TI  - The effect of subcutaneous fat on myoelectric signal amplitude and cross-talk.
AB  - The effect of subcutaneous fat on myoelectric signal amplitude and cross-talk was
      studied using finite element (FE) models of electromyogram (EMG) signal
      propagation. A FE model of the upper arm consisted of skin, fat, muscle and bone
      tissues in concentric layers. Single muscle fibre action potentials were
      simulated for muscle fibres at a variety of depths and combined to simulate
      surface EMG interference patterns. As fat layers of 3, 9 and 18 mm were added to
      the model, the RMS (root mean square) amplitude of the surface EMG signal
      directly above the centre of the active muscle decreased by 31.3, 80.2 and 90.0%,
      respectively. Similarly, surface EMG cross-talk above the region of inactive
      muscle increased as the fat layer thickness increased. The surface EMG RMS
      amplitude fell below 5% of its value above the centre of the muscle at 14
      degrees, 17 degrees, 34 degrees and 47 degrees from the edge of the active muscle
      with fat layers of 0, 3, 9 and 18 mm, respectively. An additional model was
      developed with the subcutaneous fat layer thinned from 9 mm to 3 mm in a small,
      focal region under a pair of recording electrodes. Reducing the fat layer in this
      manner caused the surface EMG amplitude at the electrodes to increase by 241% and
      decreased the EMG cross-talk by 68%; this was near the values for the 3 mm
      uniform fat layer. This demonstrates that fat reduction surgery can increase
      surface EMG signal amplitude and signal independence for improved prosthesis
      control.

PMID- 12812328
TI  - Clinical field-testing of ATLAS prosthetic system for trans-femoral amputees.
AB  - The ATLAS prosthetic system was tested on 47 trans-femoral amputees in two
      tropical areas. Although the craftsmanship was not acceptable, 46% (16/35) were
      malaligned many with the foot dorsiflexed, the user compliance was good (91%,
      32/35), and the satisfaction rate high (71%, 25/35). However, after 7-10 months
      failures occurred in 83% (29/35) mostly because of problems with the ATLAS knee
      mechanism. A modification was tested and 80% (12/15) had again failed at the knee
      after 6 (2-12) months. The ATLAS system in its current design should be abandoned
      for use for trans-femoral amputees.

PMID- 12812329
TI  - A therapeutic splint for hypertonic flexed elbow in upper motor neuron diseased
      patients.
AB  - Change in muscle tonus is characteristic of upper motor neuron disease. Upper
      limb hypertonus is mostly experienced in the flexor muscles group, causing
      abnormal fixed flexion of the elbow. This in turn leads to functional impairments
      in daily life (especially in stability while standing and walking, and in
      activities such as dressing), often accompanied by chronic pain. Extension of the
      spastic elbow is therefore a significant target goal of the rehabilitation
      process of these patients. This study presents the development of a simple, cheap
      and easy-to-use splint aimed at keeping the elbow extended. The splint is made
      out of cloth and plastic strips with longitudinal pockets sown into a double
      layer cloth surface. The splint is then wrapped and tightened around the extended
      elbow. The splint was applied to 30 patients with hypertonic flexed elbow.
      Patients were asked to keep the splint wrapped around their elbows between one to
      five hours a day, for a period of three weeks. They were instructed to shorten
      the time of use whenever they felt pain, discomfort or extended pressure on the
      arm. Most of the patients completed the trial as instructed and expressed their
      wish to carry on using it. The reported "side effects" included discomfort,
      feeling of pressure at the critical points and difficult self-application of the
      splint. The final splint model was developed based on this feedback. Its efficacy
      in keeping the elbow in an extended position, its low cost price and easy use
      makes this splint a viable and simple tool for the rehabilitation process of
      upper motor neuron disease patients.

PMID- 12812330
TI  - Psoriasis and the effect of prosthetic fitting.
AB  - This contribution presents the case histories of two patients who underwent limb
      amputation. One patient suffered from psoriasis prior to the surgery and the
      second developed psoriatic lesions post surgery. Both patients were provided with
      a prosthesis and despite the multiple cutaneous complications of the psoriasis
      both patients ambulate. It was expected that Koebner's phenomenon would create
      hardships but to date this has not happened.

PMID- 12812331
TI  - An assistive device designed to convey independent donning of a shuttle lock
      trans-tibial prosthesis for a multiple limb amputee.
AB  - This contribution describes a simple device designed to convey independent
      donning of a shuttle lock trans-tibial prosthesis for a multiple limb amputee.
      The device is made of a post with a shuttle lock mechanism at one end and a plate
      covered by rubber at the other end. This device enables correct positioning of
      the silicone liner and independent attachment to the prosthesis.

PMID- 12812332
TI  - Gait analysis in prosthetics: opinions, ideas and conclusions.

PMID- 12812333
TI  - Taxonomy: get it right or leave it alone.

PMID- 12812334
TI  - I would like to propose that the American Society of Tropical Medicine and
      Hygiene change its name.

PMID- 12812335
TI  - California state Mosquito-Borne Virus Surveillance and Response Plan: a
      retrospective evaluation using conditional simulations.
AB  - The California Mosquito-Borne Virus Surveillance and Response Plan recently was
      developed to provide a semi-quantitative means for assessing risk for western
      equine encephalomyelitis (WEE) or St. Louis encephalitis (SLE) viruses and to
      provide intervention guidelines for mosquito control and public health agencies
      during periods of heightened risk for human infection. West Nile virus recently
      has arrived in California, and the response plan also will provide a baseline for
      assessing the risk for human and equine infection with this virus. In the
      response plan, overall risk is calculated by averaging risk due to 1)
      environmental conditions, 2) adult mosquito vector abundance, 3) vector infection
      rates, 4) sentinel chicken seroconversion rates, 5) equine cases (for WEE), 6)
      human cases, and 7) the proximity of virus activity to populated areas. Overall
      risk is categorized into three levels: normal season, emergency planning, or
      epidemic conditions. We evaluated this response plan using historical data from
      years with no, enzootic, and epidemic activity of WEE and SLE in several areas of
      California to determine whether calculated risk levels approximated actual
      conditions. Multiple methods of risk calculation were considered for both
      viruses. Assessed risk based on cumulative temperature, rainfall, and runoff
      levels over the entire season provided more or equally accurate assessments than
      biweekly assessments based solely on the previous half-month. For WEE, during
      years with enzootic activity or early-season periods of years with WEE epidemic
      activity, combining horse and human cases as a single risk factor improved the
      model's ability to forecast pending WEE activity, but separating the two factors
      allowed a better indication of WEE activity during epidemics and periods with no
      activity. For SLE, assignment of higher risk to drier conditions as measured by
      rainfall and runoff yielded the most accurate representation of actual virus
      activity during all recent study periods.

PMID- 12812336
TI  - Indoor and peridomestic transmission of American cutaneous leishmaniasis in
      northwestern Argentina: a retrospective case-control study.
AB  - A case-control study was carried out during 1990-1994 to identify risk factors
      associated with American cutaneous leishmaniasis (ACL) in Santiago del Estero,
      Argentina. The study subjects consisted of 171 cases and 308 controls matched by
      age, sex, and place of residence. The analysis was performed by conditional
      logistic regression. Risk factors found to be significantly associated with ACL
      were related to indoor transmission (few rooms in the house, dirt floor, and a
      permanent opening in lieu of a window); peridomestic transmission (presence of a
      pond or woodland within 150 m of the house and an agricultural area within 200 m
      of the house); and human behavior (sleeping in the backyard, collecting water,
      bathing, and performing agricultural activities). Most transmission appears to
      have occurred indoors and in the peridomicile. These environments should be
      included in further research and control policies.

PMID- 12812337
TI  - Short report: persistence of tumor necrosis factor-alpha in situ after lesion
      healing in mucosal leishmaniasis.
AB  - Mucosal leishmaniasis (ML) is a disease characterized by intense activation of
      inflammatory cells and extensive tissue destruction. Among the cytokines involved
      in the immune response to ML, tumor necrosis factor-alpha (TNF-alpha) has
      attracted strong interest because of its roles in the modulation of the immune
      response. We studied 20 patients with ML who provided biopsy specimens before
      treatment and after lesion healing obtained by specific therapy. The biopsy
      specimens were subjected to immunohistochemical analysis for in situ
      quantification of cellular and extracellular TNF-alpha. The amount of TNF-alpha
      was significantly lower in the healed lesions compared with pretreatment biopsy
      specimens, although TNF-alpha persisted at the tissue level even after lesion
      healing. This relevant finding demonstrates for the first time an in situ tissue
      reduction of TNF-alpha after treatment and shows persistence of TNF-alpha in
      healed lesions may be related to the maintenance of an immunopathologic
      background for relapses observed in ML.

PMID- 12812338
TI  - Transmission of epidemic dengue hemorrhagic fever in easternmost Indonesia.
AB  - In April 2001, a second suspected outbreak of dengue hemorrhagic fever in the
      easternmost region of Indonesia was investigated in Merauke, a town located in
      the southeastern corner of Papua, by the Indonesian Ministry of Health and the
      U.S. Naval Medical Research Unit No. 2. Principal case criteria of hemorrhagic
      disease provided for a study enrollment of 15 clinically acute and 37
      convalescing subjects. Additionally, 32 comparable age/sex controls were selected
      from neighboring households. Laboratory diagnosis involved three testing
      methodologies: virus isolation by cell culture, a reverse transcriptase
      polymerase chain reaction (RT-PCR) assay, and serologic assays. Antibody (IgM) to
      dengue virus was detected in 27% of the acute clinical cases, 30% of the
      convalescing cases, and only 3% of the matched controls. Dengue 3 was the only
      viral serotype detected from acute serum samples by the RT-PCR. The mean +/- SD
      age of the acute and convalescing cases was 7.8 +/- 5.4 years. Overall hospital
      records accounted for 172 suspected outbreak cases, all urban residents of
      Merauke with no recent travel history outside the area. The estimated outbreak
      associated case fatality rate among all suspected dengue cases was 1.2%. A seven
      year retrospective review of hospital records in Merauke showed negligible
      disease reporting involving hemorrhagic disease prior to the outbreak.

PMID- 12812339
TI  - Differentiating dengue virus infection from scrub typhus in Thai adults with
      fever.
AB  - Dengue fever and scrub typhus are common infections in Asia that often present as
      acute febrile illness of unclear etiology. We prospectively evaluated febrile
      adults presenting to the outpatient department of a hospital in northern Thailand
      to attempt to identify distinguishing characteristics between the two infections.
      Fifty-four patients were infected with scrub typhus and 35 were infected with
      dengue virus. Dengue virus infection was associated with hemorrhagic
      manifestations, particularly bleeding from the gums, which was reported by 27% of
      the dengue patients, but by none of the scrub typhus patients (P < 0.001, by
      Fisher's exact test). A low platelet count (< 140,000/mm3) and low white blood
      cell count (< 5,000/mm3) were strongly associated with dengue infections: odds
      ratio = 26.3 (95% confidence interval [CI] = 7.4-93.2) for platelet count and 8.2
      (95% CI = 2.6-25.5) for leukocyte count. Prospective evaluations of the
      usefulness of these simple criteria to differentiate scrub typhus from dengue
      infection are needed in other areas, particularly where rapid confirmatory
      diagnostic tests are not available.

PMID- 12812340
TI  - Efficiency of dengue serotype 2 virus strains to infect and disseminate in Aedes
      aegypti.
AB  - Dengue serotype 2 (DEN-2) viruses with the potential to cause dengue hemorrhagic
      fever have been shown to belong to the Southeast (SE) Asian genotype. These
      viruses appear to be rapidly displacing the American genotype of DEN-2 in the
      Western Hemisphere. To determine whether distinct genotypes of DEN-2 virus are
      better adapted to mosquito transmission, we classified 15 viral strains of DEN-2
      phylogenetically and compared their ability to infect and disseminate in
      different populations of Aedes aegypti mosquitoes. Envelope gene nucleotide
      sequence analysis confirmed that six strains belonged to the American genotype
      and nine strains were of the SE Asian genotype. The overall rate of disseminated
      infection in mosquitoes from Texas was 27% for the SE Asian genotype versus 9%
      for the American genotype. This pattern of infection was similar in another
      population of mosquitoes sampled from southern Mexico (30% versus 13%). Together,
      these findings suggest that Ae. aegypti tends to be more susceptible to infection
      by DEN-2 viruses of the SE Asian genotype than to those of the American genotype,
      and this may have epidemiologic implications.

PMID- 12812341
TI  - Short report: assessing field vaccine efficacy for measles in famine-affected
      rural Ethiopia.
AB  - Measles is a major cause of mortality in complex emergencies. Both high
      vaccination coverage and vaccine efficacy are required to prevent major epidemics
      of measles in such situations. Evaluation of field vaccine efficacy is a critical
      but underutilized component of program monitoring in emergencies, and is
      particularly important in rural areas where the integrity of the cold chain is
      difficult to guarantee. In July 2000, we evaluated the field vaccine efficacy for
      measles vaccination by comparing the incidence of cases in vaccinated and
      unvaccinated groups during a two-stage cluster survey of 563 children in
      Ethiopia. Approximately 30% of the measles cases occurred in vaccinated children.
      Estimated field vaccine efficacy for measles was 66.9% in children 9-36 months
      old. The finding of a field vaccine efficacy for measles less than 80% warrants
      formal assessment of measles vaccine efficacy, particularly in famine emergencies
      where measles is associated with a high case fatality rate.

PMID- 12812342
TI  - Prevalence of Anaplasma phagocytophila and Borrelia burgdorferi in Ixodes
      persulcatus ticks from northeastern China.
AB  - A total of 1,345 Ixodes persulcatus ticks collected from northeastern China were
      investigated for the presence of Anaplasma phagocytophila and Borrelia
      burgdorferi by a nested polymerase chain reaction (PCR). Sixty-two (4.6%) ticks
      were positive for A. phagocytophila and 454 (33.8%) were positive for B.
      burgdorferi. Seven (0.5%) were coinfected with both agents. Sequence analysis of
      919-basepair PCR amplicons revealed three types of A. phagocytophila. Type 1 was
      identical to the published sequences of A. phagocytophilas responsible for human
      granulocytic ehrlichiosis (HGE). The other two variants differed from the HGE
      agent sequence at one and four positions, respectively. These findings imply that
      infection with A. phagocytophila poses a potential health threat to both humans
      and animals in northeastern China, and that ehrlichiosis should be considered in
      the differential diagnosis of febrile patients with a history of tick bite,
      particularly when clinical manifestations are atypical for Lyme disease.

PMID- 12812343
TI  - Spotted fever group rickettsiae in ticks from the Masai Mara region of Kenya.
AB  - We have identified for the first time Rickettsia africae, and the ticks that
      harbored them, in Kenya. A total of 5,325 ticks were collected from vegetation,
      livestock, and wild animals during two field trips to southwestern Kenya. Most
      were immature forms (85.2%) belonging to the genera Amblyomma or Rhipicephalus.
      The adults also included representatives from the genus Boophilus. Ticks were
      assessed for rickettsial DNA by a polymerase chain reaction (PCR) using primers
      for the spotted fever group (SFG)-specific rickettsial outer membrane protein A
      (rompA) gene, and positive amplicons were sequenced. While none of the immature
      ticks tested positive by PCR, 15.8% of the adult Amblyomma variegatum and less
      than 1% of the Rhipicephalus spp. were SFG positive. Sequences of amplified
      products were identified as R. africae. These findings extend the known range of
      R. africae.

PMID- 12812344
TI  - Occurrence of Bartonella henselae and Bartonella quintana in a healthy Greek
      population.
AB  - The purpose of this study was to determine the prevalence of IgM and IgG
      antibodies against Bartonella henselae and B. quintana in a healthy Greek
      population using a commercially available immunofluorescent test (Focus test).
      Five hundred healthy individuals were divided by sex into four age groups and
      three groups according to contact with cats. IgM antibodies were not detected in
      any of the subjects examined, while 99 (19.8%) and 75 (15%) were IgG seropositive
      to B. henselae and to B. quintana, respectively. No statistical difference in the
      seropositivity was observed among these groups. The IgG antibody titers ranged
      from 1/64 to 1/256 for B. henselae and from 1/64 to 1/512 for B. quintana. A high
      percentage (12.4%) of cross-reactivity between the two species was observed. Our
      data show that the prevalence of both Bartonella species in Greece is high.
      However, low IgG antibody levels are not sufficient evidence of active infection.

PMID- 12812345
TI  - In vitro reactivation of human immunodeficiency virus-1 upon stimulation with
      scrub typhus rickettsial infection.
AB  - While a number of microbial infections induce a transient burst in viral load in
      individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study
      has suggested that scrub typhus may suppress HIV-1 infection. We investigated the
      effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection
      experiments were conducted using peripheral blood mononuclear cells (PBMC)
      acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving
      highly active antiretroviral therapy (HAART) whose plasma viral load was
      undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of
      proinflammatory cytokines and beta-chemokines, and markedly down-regulated
      expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC
      resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O.
      tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART.
      These findings suggest that scrub typhus does not necessarily suppress HIV-1
      infection and does have potential to enhance HIV-1 replication.

PMID- 12812346
TI  - Dermatologic lesions in asymptomatic blood donors seropositive for human T cell
      lymphotropic virus type-1.
AB  - Dermatologic manifestations are quite common in patients with adult T cell
      leukemia/lymphoma and myelopathy/tropical spastic paraparesis associated with
      infection with human T cell lymphotropic virus type-1 (HTLV-1). In this study, we
      evaluated the dermatologic lesions of eligible blood donors in the state of Minas
      Gerais in Brazil who were seropositive but asymptomatic for infection with HTLV
      1. The study population was composed of 128 HTLV-1-seropositive individuals and
      108 seronegative controls. All individuals underwent a dermatologic evaluation.
      Biopsy specimens were obtained from abnormal and normal skin samples of
      seropositive individuals in an attempt to detect HTLV-1 in tissue samples by a
      polymerase chain reaction. Dermatologic alterations were observed more frequently
      in the seropositive group (adjusted odds ratio [OR] = 8.77, 95% confidence
      interval [CI] = 4.11-18.71). The most common skin diseases were dermatophytoses
      (adjusted OR = 3.32, 95% CI = 1.50-7.35), seborrheic dermatitis (OR = 3.53, 95%
      CI = 0.67-24.66), and acquired ichthyosis (P = 0.001). Virus was detected more
      frequently in abnormal skin samples. Dermatologic lesions probably related to
      HTLV-1 infection were diagnosed in eligible blood donors who were infected with
      this virus, who were previously considered to be asymptomatic carriers of HTLV-1.

PMID- 12812347
TI  - Short report: a new case report of human Mesocestoides infection in the United
      States.
AB  - The twenty-seventh documented case of human Mesocestoides infection, which
      corresponds to the seventh documented case in the United States, is reported. The
      case had its origin in Alexandria, Louisiana in the summer of 1998. The patient
      was a 19-month-old boy. The strobila consisted of 35 proglottids that included
      mature as well as gravid segments containing a ventral genital pore and a
      parauterine organ. After a detailed microscopic examination, the tapeworm was
      identified as belonging to the genus Mesocestoides. Mesocestoides variabilis is
      the probable species responsible for the infection, since the six cases
      previously reported in the United States were identified as this species. After
      the treatment with a single dose of praziquantel (10 mg/kg), the tapeworm
      segments were no longer detectable in the child's feces. A food-borne origin of
      this infection derived from culinary customs of the Acadian and Creole
      communities in Louisiana is proposed.

PMID- 12812348
TI  - Frequency, severity, and costs of adverse reactions following mass treatment for
      lymphatic filariasis using diethylcarbamazine and albendazole in Leogane, Haiti,
      2000.
AB  - In October 2000, 71,187 persons were treated for lymphatic filariasis using
      albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We
      documented the frequency of adverse reactions, severity and cost of treatment.
      Adverse reactions were classified as minor, moderate, or severe. Overall, 24%
      (17,421) of the treated persons reported one or more adverse reactions. There
      were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men
      outnumbered women 2:1 in reporting moderate problems. Three patients,
      representing roughly one in 25,000 persons treated, were hospitalized with severe
      adverse reactions judged to be treatment-associated by physician review. The cost
      per person treated for adverse reactions was more than twice the cost per person
      treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse
      reactions to lymphatic filariasis treatment using DEC with or without albendazole
      are uncommon. Minor and moderate reactions are more commonly reported and their
      management represents a challenge to lymphatic filariasis elimination programs.

PMID- 12812349
TI  - Comparison of polymerase chain reaction methods for reliable and easy detection
      of congenital Trypanosoma cruzi infection.
AB  - The polymerase chain reaction (PCR) is a potentially interesting diagnostic tool
      for detecting congenital Trypanosoma cruzi infection at birth. We have compared
      the sensitivity and capacity of a group of T. cruzi PCR primers in detecting the
      complete spectrum of known T. cruzi lineages, and to improve and simplify the
      detection of infection in neonatal blood. We found that the two primers,
      Tcz1/Tcz2 and Diaz1/Diaz2, which target the 195-basepair satellite repeat,
      detected all parasitic lineages with the same sensitivity. However, the intensity
      of the amplicon was somewhat higher with Tcz1/Tcz2. For other tested primers
      (nuclear DNA primers BP1/BP2, O1/O2, Pon1/Pon2, and Tca1/Tca2 and kinetoplast DNA
      primers S35'/S36' and 121/122), either the intensity of amplicons varied
      according to T. cruzi lineages or the PCR assay was less sensitive. The use of
      the Tcz1/Tcz2 primers, which target a tandem repetitive sequence, requires a
      careful determination of the appropriate amount of Taq polymerase to avoid the
      formation of smears and multiple amplicon bands. The Tcz1/Tcz2 primers resulted
      in an intense 200-basepair amplicon with DNA extracted from blood equivalent to
      0.02 parasites per assay when used with a simple DNA extraction method and of a
      low amount of Taq polymerase from a standard PCR kit. To better assess such PCR
      protocol, we assayed 311 samples of neonatal blood previously tested by
      parasitologic methods. The reliability of our PCR test was demonstrated, since
      all the 18 blood samples from newborns with congenital T. cruzi infection were
      positive, whereas the remaining samples (30 from control newborns of uninfected
      mothers and 262 of 263 from babies born to infected mothers) were negative. Since
      our PCR method is simple, reliable, robust, and inexpensive, it appears suitable
      for the detection of T. cruzi infection in neonatal blood, even in laboratories
      that are not equipped for performing the PCR.

PMID- 12812350
TI  - Co-infection with malaria and leptospirosis.
AB  - Malaria and leptospirosis are both common in the tropics. Simultaneous infections
      are possible, although not previously reported. We report two cases of malaria
      from an area of Thailand on the Thailand-Myanmar border with compelling serologic
      evidence of simultaneous acute leptospirosis. One was a case of infection with
      Plasmodium falciparum with acute and convalescent microscopic agglutination test
      (MAT) titers for Leptospira serovar icterohaemorrhagiae of 1:200 and 1:1,600,
      respectively. The other was a case of infection with P. vivax that seroconverted
      to a titer of 1:3,200 for Leptospira serovar bataviae. Additionally, there were
      five probable cases of leptospirosis with patent malaria parasitemia (three P.
      falciparum and two P. vivax) detected. Management of dual infections is
      complicated by their similar clinical presentations, and because the confirmatory
      diagnosis of malaria is readily available as opposed to that of leptospirosis.
      Treatment focusing on malaria mono-infections instead of dual infections could
      result in a delay of specific therapy for leptospirosis and possible consequences
      of serious complications.

PMID- 12812351
TI  - Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in
      vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim,
      sulfadoxine, and sulfamethoxazole.
AB  - A total of 70 Plasmodium falciparum isolates were tested in vitro against
      pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole
      (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase
      (dhps) genotypes were determined. dhfr genotypes correlated with PYR and TRM drug
      responses (r = 0.93 and 0.85). Isolates with wild-type alleles showed mean half
      inhibitory concentrations (IC50 +/- SD) of 0.10 +/- 0.10 and 0.15 +/- 0.06
      microg/100 microl for PYR and TRM. Parasites with mutations at codons 108 and 51
      alone or combined with codon 59 have IC50 of 11.46 +/- 0.86 (PYR) and 2.90 +/-
      0.59 microg/100 microl (TRM). For both drugs, the differences in the mean IC50
      between wild and mutant parasites were statistically significant (P < 0.001).
      Isolates with mixed wild and mutant alleles showed an intermediate level of
      susceptibility. Our data show partial cross-resistance between PYR/TRM and
      SDX/SMX (r = 0.85 and 0.65). Correlation was not observed between different dhps
      genotypes and the in vitro outcome to SDX and SMX (r = 0.30 and 0.34). The lack
      of correlation could be due to folates and para-aminobenzoic acid in the RPMI
      medium and the serum used to supplement the cultures.

PMID- 12812352
TI  - Association of interferon-gamma responses to pre-erythrocytic stage vaccine
      candidate antigens of Plasmodium falciparum in young Kenyan children with
      improved hemoglobin levels: XV. Asembo Bay Cohort Project.
AB  - Previous studies in animal models have revealed an association between interferon
      gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced
      sterile immunity. To determine whether IFN-gamma can serve as a marker of pre
      erythrocytic protective immunity in individuals naturally exposed to malaria, we
      characterized IFN-gamma and lymphocyte proliferative responses to previously
      defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic
      stage antigens in 107 children six months to two years old from a community-based
      birth cohort in western Kenya. We found that IFN-gamma positive responders had
      higher hemoglobin (Hb) levels and significantly reduced prevalence of severe
      malarial anemia one month after the test compared with IFN-gamma non-responders,
      suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens
      were associated with protection against malarial anemia. Children who responded
      by lymphocyte proliferation had a significantly longer time to first documented
      malaria parasitemia after birth; however, there was no correlation between the
      presence of lymphocyte proliferative response and higher Hb levels. We propose
      that IFN-gamma production could be used as a potential marker of protective
      immunity against malaria associated anemia in young children living in malaria
      holoendemic areas.

PMID- 12812353
TI  - Surveillance of in vivo resistance of Plasmodium falciparum to antimalarial drugs
      from 1992 to 1999 in Malabo (Equatorial Guinea).
AB  - From 1992-1999, we have assessed the therapeutic efficacy of three malaria
      treatment regimens (chloroquine 25 mg/kg over three days,
      pyrimethamine/sulfadoxine 1.25/25 mg/kg in one dose, and quinine 25-30 mg/kg
      daily in three oral doses over a four-, five-, or seven-day period) in 1,189
      children under age 10 at Malabo Regional Hospital in Equatorial Guinea. Of those
      children, 958 were followed up clinically and parasitologically for 14 days. With
      chloroquine, the failure rate varied from 55% in 1996 to 40% in 1999; the early
      treatment failure rate increased progressively over the years, from 6% in 1992 to
      30% in 1999. With pyrimethamine/sulfadoxine, the failure rate varied from 0% in
      1996 to 16% in 1995. The short quinine treatment regimens used in 1992 and 1993
      (4 and 5 days, respectively) resulted in significantly higher failure rates (19%
      and 22%, respectively) than the 7d regimen (3-5.5%). We conclude that: a) failure
      rates for chloroquine are in the change period (> 25%), and urgent action is
      needed; b) pyrimethamine/ sulfadoxine failure rates are in the alert period (6
      15%), and surveillance must be continued; and c) quinine failure rates are in the
      grace period (< 6%), so quinine can be recommended.

PMID- 12812354
TI  - Forest malaria in Chhindwara, Madhya Pradesh, central India: a case study in a
      tribal community.
AB  - Parasitologic and entomologic cross-sectional surveys were carried out during an
      outbreak of malaria between December 1998 and August 2000 in forest villages near
      the Mohkhed Primary Health Center in the Chhindwara District of Madhya Pradesh in
      central India. In December 1998, surveys showed that more than 70% of the fever
      cases had malaria, with 87% of the malaria caused by Plasmodium falciparum. The
      rate of enlarged spleens in children was 74.5%. In November 1999, 58% of the
      inhabitants were infected with malaria, with 80% of these cases caused by P.
      falciparum. Chloroquine resistance was seen in 23% of the cases. Anopheles
      culicifacies was the dominant mosquito species in all surveys (70-85%) and was
      resistant to DDT. The results indicate that the incidence of malaria in
      Chhindwara has increased gradually from 0.31 per 1,000 in 1990 to 6.75 per 1,000
      in 2000. Improved access to treatment facilities, combination therapy, and vector
      control using an effective insecticide appear to be the most promising methods
      for controlling malaria in this region.

PMID- 12812355
TI  - Efficacy of mefloquine and a mefloquine-artesunate combination therapy for the
      treatment of uncomplicated Plasmodium falciparum malaria in the Amazon Basin of
      Peru.
AB  - In the Amazon Basin of Peru, more than 50% of patients with uncomplicated
      Plasmodium falciparum malaria fail to respond to treatment with chloroquine or
      sulfadoxine-pyrimethamine. To assist the National Malaria Control Program in
      identifying an alternative first-line therapy for this region, we conducted a
      trial of the safety and efficacy of mefloquine (MQ) compared with mefloquine
      artesunate (MQ-AS) combination therapy. Patients with uncomplicated P. falciparum
      infections between the ages of 5 and 50 years were randomly assigned to be
      treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS
      (4 mg/kg/day for three days). A total of 98 patients were enrolled and followed
      for 28 days. None of the 47 patients who received MQ alone or the 51 patients who
      received MQ-AS combination therapy had recurrences of parasitemia during the 28
      day follow-up period. Asexual parasite densities decreased significantly more
      rapidly and the proportion of patients with gametocytes was significantly lower
      on days 3-21 in the MQ-AS group than in patients treated with MQ alone. All
      patients tolerated the medication well. Based on the results of this study and
      with the objective of slowing the development of resistance, the Peruvian
      Ministry of Health has decided to revise its malaria treatment policy and
      recommend combination therapy with MO-AS as the new first-line treatment of
      uncomplicated P. falciparum malaria in the Amazon region.

PMID- 12812356
TI  - Genetic diversity and multiple infections of Plasmodium vivax malaria in Western
      Thailand.
AB  - Using two polymorphic genetic markers, the merozoite surface protein-3alpha (MSP
      3alpha) and the circumsporozoite protein (CSP), we investigated the population
      diversity of Plasmodium vivax in Mae Sod, Thailand from April 2000 through June
      2001. Genotyping the parasites isolated from 90 malaria patients attending two
      local clinics for the dimorphic CSP gene revealed that the majority of the
      parasites (77%) were the VK210 type. Genotyping the MSP3-alpha gene indicated
      that P. vivax populations exhibited an equally high level of polymorphism as
      those from Papua New Guinea, a hyperendemic region. Based on the length of
      polymerase chain reaction products, three major types of the MSP-3alpha locus
      were distinguished, with frequencies of 74.8%, 18.7%, and 6.5%, respectively. The
      13 alleles distinguished by restriction fragment length polymorphism analysis did
      not show a significant seasonal variation in frequency. Genotyping the MSP-3alpha
      and CSP genes showed that 19.3% and 25.6% of the patients had multiple
      infections, respectively, and the combined rate was 35.6%. Comparisons of MSP
      3alpha sequences from nine clones further confirmed the high level of genetic
      diversity of the parasite and also suggested that geographic isolation may exist.
      These results strongly indicate that P. vivax populations are highly diverse and
      multiple clonal infections are common in this malaria-hypoendemic region of
      Thailand.

PMID- 12812357
TI  - The efficacy of combined mefloquine-artesunate versus mefloquine-primaquine on
      subsequent development of Plasmodium falciparum gametocytemia.
AB  - An open randomized controlled study of mefloquine-artesunate and mefloquine
      primaquine for the treatment of uncomplicated Plasmodium falciparum malaria was
      carried out in Kanchanaburi in the Saiyok District in western Thailand. Weekly
      parasite counts from thick and thin blood films were done for six weeks. The
      gametocyte carriage rate was calculated and compared between the two treatment
      groups. Gametocytes on presentation, recrudescent infection, and reinfection were
      the significant factors associated with subsequent development of gametocytemia.
      It is the increased propensity of recrudescent infections to produce gametocytes
      that drives drug resistance. The results of this study confirmed that the
      complete eradication of a sexual forms of P. falciparum by effective antimalarial
      treatment, but not by combination treatment with primaquine, is the most
      effective means to prevent subsequent gametocytemia.

PMID- 12812358
TI  - Performance of the OptiMAL test for malaria diagnosis among suspected malaria
      patients at the rural health centers.
AB  - The OptiMAL test detects both Plasmodium falciparum and P. vivax malaria
      infections. In this study, we evaluated the performance of the OptiMAL test at
      the Basic Health Units (BHUs) and the District Health Quarter (DHQ) Center in
      rural villages of Punjab, Pakistan that provide minimal health services. Two sets
      of blood specimens obtained from 930 suspected malaria patients attending these
      BHUs were tested at BHUs and the DHQ Center by microscopy and the OptiMAL test.
      At the BHUs, 231 (25%) of the patients were positive by microscopy and 278 (30%)
      patients tested positive by the OptiMAL test. At the DHQ Center, microscopic
      analysis of a second set of specimens from the same patients confirmed the
      malaria infection in 386 (42%) patients and the OptiMAL test result was positive
      in 300 (32%) patients. To determine the performance of OptiMAL test at the BHUs
      and the DHQ Center, all data were compared with microscopy results obtained at
      the DHQ Center. The OptiMAL test results for P. falciparum at the BHUs were
      comparable to those of the OptiMAL test at the DHQ Center. However, the
      sensitivity, positive predictive value (PPV), and negative predictive value (NPV)
      of the OptiMAL test were considerably lower for P. vivax infections than for P.
      falciparum infections, irrespective of whether the test was performed at the BHUs
      or at the DHQ Center (P. falciparum: sensitivity = 78-85%, PPV = 89-97%, NPV = 96
      98%; P. vivax: sensitivity = 61-76%, PPV = 88-95%, NPV = 90-93%). The OptiMAL
      test also detected a number of false-positive and false-negative results at both
      the BHUs and the DHQ Center. The false-positive results ranged from 1% to 2%;
      however, the number of false-negative results was much higher (BHUs: P.
      falciparum = 22%, P. vivax = 39%; DHQ Center: P. falciparum = 15%, P. vivax =
      24%). In conclusion, these results, when combined with other advantages of the
      OptiMAL test, suggest that this test can be used by relatively inexperienced
      persons to diagnose malaria infection in rural areas where facilities for
      microscopy are not available.

PMID- 12812359
TI  - Novel sigma binding site ligands as inhibitors of cell proliferation in breast
      cancer.
AB  - Sigma receptors, namely sigma1 and sigma2, have been shown to be expressed in a
      variety of human cell lines playing a role in cell growth. In the human breast,
      they are absent in normal mammary tissue but expressed in tumors, particularly in
      the proliferating stage. The study presented here concerns nine newly synthesized
      ligands for sigma receptors. The compounds are of general structure consisting
      of: five (1alpha/1beta-arylalkyl)quinolizidines including two thioisosteres and
      four spiro-[3,4-dihydro-1,2,4-benzotriazino-3,4'-(1'-substituted) piperidines].
      These compounds exhibited varying degrees of affinity for sigma receptors and
      were able to inhibit the growth of MCF-7 and MDA-MB 231 human breast cancer cell
      lines, in vitro. Good to moderate binding to at receptors occurred with all
      tested ligands. However, affinity for sigma2 appeared more evident with compounds
      FN/C-2 and FN/C-4 (spiro-[3,4-dihydro-1,2,4-benzotriazino-3,4'-(1'-substituted)
      piperidines] derivatives). In addition, higher cytotoxic activity of FN/C-2 and
      FN/C-4 with IC50 values below 100 microM in MCF-7 and lower than 40 microM in MDA
      MB 231 was revealed. The data from the current study show that these novel sigma
      receptor ligands exhibit interesting cytotoxic activity and suggest their
      potential for development as antitumor agents.

PMID- 12812360
TI  - Flavonoids as inhibitors of MRP1-like efflux activity in human erythrocytes. A
      structure-activity relationship study.
AB  - The potency of flavonoids (isoflavones, flavones, and flavanones) to inhibit
      efflux of 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human
      erythrocytes was investigated. Structure-activity relationship analysis showed
      that the strongest inhibitors were found among flavanones bearing a hydrophobic
      prenyl, geranyl, or lavandulyl group at position 8 (and hydroxyl groups at 5 and
      7) in ring A. A prenyl group at position 5' or stilbene at positions 4'-5' in
      ring B further seemed to increase inhibitor potency. The most efficient
      flavanones, euchrestaflavanone A and sophoraflavanone H, were approximately 20
      times more efficient than genistein, and induced 50% inhibition of BCPCF efflux
      (IC50) at 3 microM (60 min, 37 degrees C). This is comparable to IC50 of
      benzbromarone (4 microM) and lower than IC50 of indomethacin (10 microM), both
      known MRP1 (ABCC1) inhibitors. It is suggested that BCPCF efflux is mainly due to
      MRP1 activity. Our results indicate that flavonoid molecular structure provides a
      promising base for development of potent MRP1 inhibitors.

PMID- 12812361
TI  - Three-dimensional pharmacophore mapping of certain anticancer alpha-methylene
      gamma-butyrolactones.
AB  - A definition of pharmacophore hypotheses for certain anticancer alpha-methylene
      gamma-butyrolactones was carried out by consideration of a three-dimensional
      model that correlates the chemical structures of a series of alpha-methylene
      gamma-butyrolactones with their cytostatic activity. Training sets consisting of
      20 alpha-methylene-gamma-butyrolactones were selected in each case on the basis
      of the information content of the structures and the activity data as required by
      the HypoGen program in the Catalyst software. In this case, the best
      pharmacophore in terms of statistics and predictive value consisted of four
      features: two hydrogen bond acceptors (HBA), one hydrophobic (HP) feature, and
      one aromatic ring (AR) feature. The selected pharmacophore hypothesis yielded a
      correlation coefficient of 0.942 with a cost difference (null cost minus total
      cost) of 40.342. The pharmacophore was validated on a set of test compounds. This
      validation study provided confidence for the usefulness of the selected
      pharmacophore model to identify compounds with diverse structures from a database
      search. This investigation has demonstrated a practical approach toward the
      development of anticancer lead compounds through a three-dimensional
      pharmacophore mapping.

PMID- 12812362
TI  - Detection of labile anthracycline-DNA adducts by real-time PCR.
AB  - Barminomycin was employed as a model anthracycline that yields thermally stable
      drug-DNA adducts. Real-time PCR was utilized for the detection of these
      barminomycin-DNA adducts at drug levels as low as 100 nM in a cell-free assay
      system, with the lowest level of detection at approximately 20 nM. By contrast,
      doxorubicin-DNA adducts are heat labile and their levels were underestimated by
      conventional real-time PCR unless the DNA denaturation temperature was lowered by
      the addition of glycerol. Doxorubicin-DNA adduct levels of 5.5 per 10 kb were
      detected by real-time PCR (in the presence of 24% glycerol) following treatment
      with 0.5 microM doxorubicin (and 2 mM formaldehyde), considerably more sensitive
      than that detected by a gene-specific Southern-based procedure. Both the absolute
      fluorescence intensity in the linear PCR amplification range and the crossing
      point method provided useful dose-dependent estimates of adduct levels. The time
      required for a complete real-time PCR analysis of drug-induced adduct levels was
      approximately 40 min, and this may ultimately provide oncologists with a rapid
      means with which to monitor drug-DNA adduct levels in patients under treatment
      with anthracyclines. Responses to these drugs could be quickly and efficiently
      monitored in patients, thereby facilitating optimization of drug dosages as well
      as early detection of resistance to these agents.

PMID- 12812363
TI  - Mode of cell death induced in Chinese hamster cells by sequence-selective DNA
      minor groove binding nitrogen mustards: comparison with untargeted mustards and
      with Hoechst 33342.
AB  - The clinical antitumor efficacy of nitrogen mustards such as chlorambucil may
      relate to their ability to cause programmed cell death (apoptosis), probably
      through their DNA cross-linking properties. In contrast, bisbenzimidazoles such
      as Hoechst 33342 interact noncovalently with the minor groove of DNA, and appear
      to cause apoptosis in a fundamentally different way, which may involve the
      inhibition of topoisomerase (topo) I enzymes. A series of DNA minor groove
      binding nitrogen mustards with selective DNA affinity and in vivo antitumor
      activity in animal models was studied. Although two examples of such compounds
      proved to inhibit topo I enzymes in vitro, they were equally toxic towards topo I
      proficient and- deficient strains of yeast, suggesting that topo I inhibition was
      not involved in cell killing. Flow cytometric analysis of Chinese hamster cells
      highlighted the differences in the propensity to cause apoptosis by chlorambucil
      compared with Hoechst 33342, revealing two distinct apoptotic populations in
      cells treated with the latter drug. Unexpectedly, the bisbenzimidazole mustards
      showed a novel peak of apoptotic activity, distinct from that shown by either
      parent drug. Exploring these different mechanisms of apoptosis may provide new
      directions for the development of antitumor drugs.

PMID- 12812364
TI  - Synthesis and antimelanoma activity of tertiary amide analogues of N-acetyl-4-S
      cysteaminylphenol.
AB  - The biosynthetic pathway to melanin is a realistic target for therapeutic
      intervention in the development of new drugs to combat malignant melanoma. N
      Acetyl-4-S-cysteaminylphenol (1) is an analogue of a biosynthetic intermediate in
      the pathway to melanin. It probably acts as a prodrug and is oxidized selectively
      in melanocytes to an o-quinone, which can alkylate cellular nucleophiles
      resulting in interference with cell growth and proliferation. We previously
      synthesized a range of more lipophilic analogues of 1 by varying the acyl portion
      and introducing substitution alpha to the nitrogen. Most of the new compounds
      displayed greater cytotoxicity than the original lead compound 1. We have now
      prepared 12 new compounds with varying acyl portions and three different
      substituents on the nitrogen of the amide in order to increase lipophilicity and
      to reduce the possibility of hydrolysis of the amides. Most of the tertiary
      amides showed greater cytotoxicity towards five representative melanoma cell
      lines than the parent secondary amide. The highest cytotoxicity, comparable to
      cisplatin, was observed for the benzyl substituted compounds 4, 8, 12, and 16 and
      the cyclohexylacetamide derivatives 13-15 against these five cell lines. The
      moderate activity of 13-16 against SK-Mel-24 (non-tyrosinase containing) and an
      ovarian cell line suggests that interference with the melanin pathway may not be
      the only mode of action of these new compounds.

PMID- 12812365
TI  - Spotlight: re-evaluating replicating organelles.

PMID- 12812366
TI  - The versatile Dictyostelium discoideum. Meeting report: International
      Dictyostelium Conference 2002.

PMID- 12812367
TI  - Horizontal gene transfer and the evolution of parasitic protozoa.

PMID- 12812368
TI  - Regulation of Dictyostelium guanylyl cyclases.

PMID- 12812369
TI  - Making a robust biomolecular time scale for phylogenetic studies.
AB  - The further evolution of informational molecular sequences should depend on the
      number of viable alternatives possible for the sequences as set by selection, the
      unrepaired mutation rate, and time. Most biomolecular clocks are based on
      Kimura's nearly neutral mutation random-drift hypothesis. This clock assumes that
      informational sequences are in equilibrium, i.e., the nucleotides mutate at a
      uniform rate and the number of nucleotides unconstrained by selection remains
      constant. Correcting for deviations from these assumptions should produce a more
      accurate clock. Informational molecules probably formed from polynucleotides
      having some other function such as nitrogen or nucleotide storage, thus being
      initially functionally unselected. At any time the rate of development of
      functionality in a protein may be expected to be proportional to the number of
      viable alternatives of sequence in its potentially interacting regions. Assuming
      the rate of unrepaired mutations is constant, these clocks should exponentially
      slow as they evolve, each with a different rate toward individual equilibria.
      Also if the degree of selection changes, its clock rate should change. For a more
      precise clock two approaches are suggested to estimate these time dependent
      changes in evolutionary rate. An improved clock could improve estimation of
      phylogeny and put a time scale on that phylogeny.

PMID- 12812370
TI  - Discovery of a group I intron in the SSU rDNA of Ploeotia costata (Euglenozoa).
AB  - The gene coding for the small ribosomal subunit RNA of Ploeotia costata contains
      an actively splicing group I intron (Pco.S516) which is unique among
      euglenozoans. Secondary structure predictions indicate that paired segments P1
      P10 as well as several conserved elements typical of group I introns and of
      subclass IC1 in particular are present. Phylogenetic analyses of SSU rDNA
      sequences demonstrate a well-supported placement of Ploeotia costata within the
      Euglenozoa; whereas, analyses of intron data sets uncover a close phylogenetic
      relation of Pco.S516 to S-516 introns from Acanthamoeba, Aureoumbra lagunensis
      (Stramenopila) and red algae of the order Bangiales. Discrepancies between SSU
      rDNA and intron phylogenies suggest horizontal spread of the group I intron.
      Monophyly of IC1 516 introns from Ploeotia costata, A. lagunensis and rhodophytes
      is supported by a unique secondary structure element: helix P5b possesses an
      insertion of 19 nt length with a highly conserved tetraloop which is supposed to
      take part in tertiary interactions. Neither functional nor degenerated ORFs
      coding for homing endonucleases can be identified in Pco.S516. Nevertheless,
      degenerated ORFs with His-Cys box motifs in closely related intron sequences
      indicate that homing may have occurred during evolution of the investigated
      intron group.

PMID- 12812371
TI  - Effect of alteration in the global body plan on the deployment of morphogenesis
      related protein epitopes labeled by the monoclonal antibody 12G9 in Tetrahymena
      thermophila.
AB  - We have employed monoclonal antibodies to reinvestigate the janus mutants of the
      ciliate Tetrahymena thermophila, which cause reversal of circumferential polarity
      on the dorsal surface of the cell. This reversal brings about frequent ectopic
      expression of ventral cortical landmarks, such as a "secondary" oral apparatus,
      on the dorsal surface. The principal antibody employed, FXXXIX-12G9, immunolabels
      both transient cortical structures not directly associated with basal bodies (the
      fission line and the postoral meridional filament) and more permanent structures
      (apical band and oral crescent) that are associated with basal bodies. 12G9
      immunolabeling of janus cells has revealed additional phenotypes, including
      disorder of ciliary rows. Further, this labeling has shown that the postoral
      meridional filament is often expressed and the apical band is frequently
      interrupted on the mid-dorsal surface of janus cells irrespective of whether or
      not these cells express a "secondary" oral apparatus. Of the permanent structures
      revealed by 12G9 immunofluorescence, modifications of the oral crescent (OC) are
      associated with prior modifications in the development of basal body-containing
      structures in the secondary oral apparatus. The formation of the apical band (AB)
      is also commonly abnormal in janus cells; analysis of specific abnormalities
      shows that the AB depends both on its initiation at a specific site near the
      anterior basal body of apical basal body couplets and on the normal location of
      these couplets just posterior to the fission line. We also have uncovered an
      intriguing difference in the reactivity of apical-band filaments to the 12G9
      antibody in the two non-allelic janus mutants (janA1 and janC2) that we have
      investigated. Taken together, our observations indicate that the formation of new
      cellular structures at division depends both upon pre-existing cytoskeletal
      structures and upon the positional information provided by large-scale cellular
      polarities.

PMID- 12812372
TI  - Mixotrophy of a photosynthetic flagellate viewed from an optimal foraging
      perspective.
AB  - Mixotrophy, a combination of phototrophic and phagotrophic nutrition, has been
      found in several classes of phytoplankton (Booras et al. 1988, Jones 2000) and
      appears to be a successful evolutionary strategy. Heterotrophic nutrition of
      phytoplankton has been suggested to be an important source of mineral nutrients
      (Nygaard and Tobiesen 1993). Potentially limiting mineral nutrients, particularly
      phosphorus (P), are often several orders of magnitude more concentrated in the
      biomass of food organisms of mixotrophs (e.g. in bacteria) than in the dissolved
      phase (Vadstein 2000). We used radioactive tracer experiments to show that the
      simultaneous uptake of P from dissolved inorganic and particular P sources by the
      marine phytoflagellate Chrysochromulina polylepis followed basic predictions of
      optimal foraging theory (Stephens and Krebs 1986). Chrysochromulina takes up its
      P rather unselectively from both bacterial P and dissolved P sources at low
      dissolved P concentrations, while it becomes more selective at higher dissolved
      inorganic P (DIP) concentrations. The onset of mixotrophic processes was
      dependent on DIP concentrations. These findings support the view of mixotrophy as
      a strategy of nutrient uptake in nutrient poor (oligotrophic) pelagic
      environments (Nygaard and Tobiesen 1993) and show that ideas of optimal foraging
      can be applied to unicellular organisms.

PMID- 12812373
TI  - Phylogeny and taxonomic revision of plastid-containing euglenophytes based on SSU
      rDNA sequence comparisons and synapomorphic signatures in the SSU rRNA secondary
      structure.
AB  - Sequence comparisons and a revised classification of the Euglenophyceae were
      based on 92 new SSU rDNA sequences obtained from strains of Euglena, Astasia,
      Phacus, Trachelomonas, Colacium, Cryptoglena, Lepocinclis, Eutreptia,
      Eutreptiella and Tetreutreptia. Sequence data also provided molecular signatures
      for taxa from genus to class level in the SSU rRNA secondary structure, revealed
      by a novel approach (search for non-homoplasious synapomorphies) and used for
      taxonomic diagnoses. Photosynthetic euglenoids and secondary heterotrophs formed
      a clade, designated as Euglenophyceae (emend.) with two orders: Euglenales and
      Eutreptiales. The mostly marine Eutreptiales (Eutreptia, Eutreptiella; not
      Distigma) comprised taxa with two or four emergent flagella (the quadriflagellate
      Tetreutreptia was integrated within Eutreptiella). The Euglenales (freshwater
      genera with < or = one emergent flagellum) formed nine clades and two individual
      branches (single strains); however, only two clades were congruent with
      traditional genera: Trachelomonas (incl. Strombomonas) and Colacium. Euglena was
      polyphyletic and diverged into four independent clades (intermixed with Astasia,
      Khawkinea and Lepocinclis) and two individual branches (e.g. E. polymorpha).
      Phacus was also subdivided into Phacus s. str. and two combined lineages (mixed
      with Lepocinclis spp. or Cryptoglena). In consequence, Euglena (s. str.), Phacus
      and other genera were emended and one lineage (mixed Phacus/Lepocinclis-clade)
      was recognized as the previously neglected genus Monomorphina Mereschkowsky
      (1877). The sister clade of Phacus s. str. (mixed Euglena/Lepocinclis-clade) was
      identified as Lepocinclis Perty (emended).

PMID- 12812374
TI  - Phylogenetic diversity and whole-cell hybridization of oxymonad flagellates from
      the hindgut of the wood-feeding lower termite Reticulitermes flavipes.
AB  - SSU rRNA genes of oxymonad protists from the hindgut of the wood-feeding termite
      Reticulitermes flavipes were PCR-amplified using a newly designed oxymonad
      specific forward primer and a newly designed reverse primer specific for termite
      gut flagellates. After cloning, the clone library was sorted into four groups by
      RFLP analysis and nearly full-length SSU rRNA gene sequences were obtained for
      representative clones from each group. Phylogenetic analysis revealed that
      sequences of all four groups formed a monophyletic cluster with the only other
      existing SSU rRNA gene sequence of oxymonads. Using whole-cell hybridization with
      clone-specific fluorescently labeled probes, each of the four clone groups could
      be assigned to a specific morphotype, which were identified as Dinenympha
      gracilis, Dinenympha fimbriata, and so-far undescribed species of Pyrsonympha and
      Dinenympha. Our results demonstrate that the morphological variety of oxymonads
      is not caused by the presence of different developmental stages of the same
      organism, but that the various morphotypes represent different species.

PMID- 12812375
TI  - The protistologist Ernst Georg Pringsheim and his four lives.

PMID- 12812376
TI  - Rheology: an overlooked component of vascular disease.

PMID- 12812377
TI  - Management of thrombotic and cardiovascular disorders in the new millenium.
AB  - Anticoagulants and antithrombotic drugs have played a key role in the
      prophylaxis, treatment and surgica/interventional management of thrombotic and
      cardiovascular disorders. There are several newer drugs which are currently
      developed for the anticoagulant management of cardiovascular diseases in both the
      medical and surgical indications. These include the low molecular weight heparins
      (LMWHs), antithrombin agents such as the Hirudin, Hirulog and Argatroban and
      indirect and direct anti-Xa drugs, represented by Pentasaccharide (Arixtra) and
      DX 9065a, respectively. Several other agents such as the natural and recombinant
      anti-Xa drugs and anti-tissue factor agents are also developed. The antiplatelet
      agents include Clopidogrel, Cilostazol, Anplag and GP IIb/IIIa inhibitors. For
      the subcutaneous indications, unfractionated heparin is gradually replaced by the
      low molecular weight heparins (LMWHs). LMWHs such as the Enoxaparin and
      Dalteparin are commonly used for the management of acute coronary syndrome. These
      drugs have been approved for the treatment of unstable angina and are currently
      undergoing rigorous trials for interventional indications. Arixtra is also
      developed for various subcutaneous indications. However, it exhibits lower
      anticoagulant effects and may not be optimal for intravenous and interventional
      purposes. At a higher dosage when administered intravenously the LMWHs produce
      varying degrees of anticoagulation at relatively lower activated clotting times
      (150-200). Several studies in vascular and cardiovascular interventions have
      shown that even at a relatively lower anticoagulant level the LMWHs are as
      effective as unfractionated heparin at the recommended dosages which produce a
      relatively higher level of anticoagulation (ACT > 200 secs.). Thus, these agents
      are currently developed for interventional and surgical indications. It should be
      emphasized that different LMWHs produce different degrees of anticoagulation and
      should therefore be individually optimized for a given interventional or surgical
      purposes. At a relatively high dosage the levels of LMWHs can be measured by
      using the ACT and APTT. When administered with such GP IIb/IIIa inhibitors as the
      Abciximab, Aggrastat or Eptifibratide, these drugs may require dosage adjustment
      However, since the introduction of the front loading of Clopidogrel, the
      unqualified use of GP IIb/IIIa is debated. LMWHs will find expanded indications
      in both the medical and surgical management of patients with cardiovascular
      disorders including atrial fibrillation and congestive heart failure. The only
      approved anti-Xa drug is represented by a synthetic heparinomimetic, namely,
      Arixtra. This drug is given for the prophylaxis of post orthopedic indications.
      This agent is undergoing additional clinical trials in the management of coronary
      artery diseases. Because of the dependence on antithrombin III (AT) and the sole
      anti-Xa effects, it has a narrow therapeutic index and its efficacy in this
      indication may be limited. Additional clinical trials are needed at this time to
      validate the clinical potential of this drug. The antithrombin agents (Hirudin,
      Hirulog and Argatroban) were initially developed for arterial indications.
      However, these agents are approved as a substitute anticoagulant in patients with
      heparin induced thrombocytopenia (HIT) and PCI. Currently an of these agents are
      being developed for surgical and interventional use. However, since there is no
      available antidote at this time, the development is somewhat limited. The
      antithrombin agents may be useful in patients with HIT which require further
      clinical validation. Many other anti-Xa agents are also developed. Most of these
      can be given parenterally. However, the clinical data is somewhat limited.
      Similarly, several of the new antiplatelet drugs can be administered parenterally
      and may be useful in CAD. Since most of these newer anticoagulant and
      antithrombotic drugs are mono-therapeutic their therapeutic index is rather
      limited. Only in combination these agents can mimic heparins. At this time it is
      safe to state that heparin and its LMW derivatives will remain the anticoagulant
      of choice for cardiovascular indications until these newer agents have been
      validated in extended clinical trials in polytherapeutic settings.

PMID- 12812378
TI  - Flight microangiopathy on long-haul flights: prevention of edema and
      microcirculation alterations with Venoruton.
AB  - The aim of this study was the evaluation of the effects of Venoruton (HR) on the
      prevention and control of flight microangiopathy and edema in subjects with
      varicose veins flying for more than 7 hours. A group of 80 patients with varicose
      veins, edema, and initial skin alterations due to chronic venous hypertension
      were included. Measurements of skin laser Doppler (LDF) resting flux (RF), PO2
      and rate of ankle swelling (RAS), were made before and after the flights (within
      2 hours before the flights and within 2 hours after the flights). The length of
      the flights was between 7 and 9 hours; all seats were in coach class. The two
      groups (treatment and control) were comparable for age and sex distribution. The
      variation (decrease) in PO2 was significant in both groups. In subjects treated
      with HR the decrease in PO2 was smaller (p < 0.05). The decrease in LDF-RF was
      significant in both groups with a higher flux at the end of the flight in the
      treated subjects (p < 0.05). The venoarteriolar response was decreased at the end
      of the flights. The decrease was less evident in the treatment group (p < 0.05).
      The increase in RAS was significant in the control group while it was limited in
      the HR group. In conclusion, HR is useful for reducing the increased capillary
      filtration and in controlling edema in patients with chronic venous disease in
      long-haul flights. HR is effective to control flight microangiopathy associated
      with edema.

PMID- 12812379
TI  - The effect of a loading dose (300 mg) of clopidogrel on platelet function in
      patients with peripheral arterial disease.
AB  - Clopidogrel acts on the P2Y12 adenosine diphosphate (ADP) purinergic receptors on
      human platelets. The aim of this study was to establish if a loading dose of
      clopidogrel inhibits platelet activation in patients with peripheral arterial
      disease (PAD). Two indices of platelet activation were considered: platelet shape
      change (PSC) and aggregation. Citrated blood was collected from ten PAD patients
      who were not on aspirin, at baseline (0 hours) and 2 and 4 hours after these
      patients ingested a loading dose (300 mg) of clopidogrel. ADP (5 micromo/L)
      induced platelet aggregation in whole blood was inhibited after 2 hours (free
      platelet count, 47% +/- 19% vs. 68% +/- 15%; p < or = 0.001) and 4 hours (47% +/-
      19% vs. 66% +/- 16%; p < or = 0.001). There was also a significant inhibition of
      5- hydroxytryptamine (SHT, 5.0 micromol/L)-induced platelet aggregation at 2
      hours. This trend was also observed for 10-micomol/L ADP-induced aggregation. ADP
      (0.3-0.4 micromol/L)-induced PSC was significantly inhibited at 4 hours (increase
      in median platelet volume, 6.3%, 1.8-10.7 vs. 1.2%, 0-5.3; p = 0.01). 5HT (0.5
      micromol/L)-induced PSC at 4 hours was also significantly inhibited (8.1, 5.3
      10.6 vs. 3.0, 0-8.2; p = 0.03). A loading dose of clopidogrel (300 mg) inhibits
      platelet activation in PAD patients, as early as 2 hours. To the authors'
      knowledge, no other study considered the effect of a loading dose of clopidogrel
      in PAD.

PMID- 12812380
TI  - Atherosclerosis and secondary deep vein thrombosis: a difficult correlation.
AB  - The aim of this study was to verify the degree of atherosclerosis in a group of
      subjects affected by secondary deep vein thrombosis and in a matched control
      group. Sixty-three patients were studied. Of these, 19 were cases (mean age 62.2
      +/- 1.2) and 16 were controls (mean age 59.3 +/- 2.7). Twenty-eight were excluded
      because they were affected by hyperhomocysteinemia. The arterial tree was
      examined by means of echo color Doppler, and the intima media thickness and the
      presence of and degree of plaques bilaterally in the carotid and femoral artery
      and abdominal aorta were measured with a computerized method. No difference was
      found in the 2 groups as concerns intima media thickness or plaques in the
      arterial district explored. Secondary deep vein thrombosis is not a greater risk
      factor for atherosclerosis.

PMID- 12812381
TI  - Changes in prescription patterns of oral contraceptives in a northern Italian
      province: relation with venous thromboembolism.
AB  - Oral contraceptives (OC) are a definite risk for venous thrombosis. It is
      commonly accepted that they cause a fourfold increased risk of thrombosis
      compared to non-users. The prescription patterns were evaluated from 1990 to 2000
      in a northern Italian province (province of Padua). This province is typical of
      other northern Italian provinces. As a consequence, it can be safely assumed that
      the observations gathered may apply to the entire north of Italy. During these
      years, a sharp increase in the use of OC was noted. Furthermore, around 1995 to
      1996, a marked switch toward the use of preparations containing third-generation
      progestins was noted. During the past few years of the observation period,
      approximately 80% of women use preparations containing third-generation
      progestins. During the same period, an increased incidence of episodes of venous
      thromboembolism (VTE) was noted. The increase in the prevalence of VTE episodes
      appeared to be proportional to the increased use of OC, regardless of the type of
      progestin contained in the oral contraceptive preparations.

PMID- 12812382
TI  - A model for clinical estimation of perioperative hemorrhage.
AB  - The purpose of this study was to assess the accuracy of estimated blood loss
      (EBL) as a reliable predictor of actual blood loss during orthopedic procedures.
      Between 1999 and 2002, 198 orthopedic cases were reviewed. A retrospective review
      compiled preoperative and postoperative demographic and laboratory data from the
      surgical patients. Estimated blood loss data was collected from the perioperative
      and anesthesia reports. Statistical analysis of EBL vs. change in hemoglobin
      yielded a correlation coefficient of 0.189 and a p value of 0.008. We used
      multiple linear regression to obtain a model to predict change in hemoglobin
      based on EBL and the intravenous fluids received. The model is as follows:
      predicted change in hemoglobin = 1.001 x estimated blood loss (in liters) + 0.441
      x intravenous fluids received (in liters) + 2.334. The study population included
      198 patients, 126 males and 72 females, who met our inclusion criteria. The mean
      age was 68.1 years (range: SD 12.5), including 126 males (64%) and 72 females
      (37%). The mean amount of perioperative intravenous fluids given was 1,732 mL
      (SD: 773). The mean surgical time was 64.8 minutes (SD: 23.1). The mean
      preoperative hematocrit and hemoglobin levels were 40.9 g/dL (SD: 4.3) and 13.9
      g/dL (SD: 1.6), respectively. The mean postoperative hematocrit and hemoglobin
      levels were 32.0 g/dL (SD: 6.0) and 10.7 g/dL (SD: 1.6), respectively. The mean
      difference of preoperative hemoglobin vs. postoperative hemoglobin was 3.3 g/dL
      (SD 2.1). In this retrospective study, clinical estimation of blood loss was
      closely correlated with actual change in perioperative hemoglobin. Accurately
      predicting the postoperative hemoglobin level may prevent many unnecessary blood
      transfusions and related complications.

PMID- 12812383
TI  - Value of thromboelastography in the assessment of platelet function.
AB  - Thromboelastography (TEG) is a useful measure of coagulation. Modified TEG (that
      is with the addition of a GP IIb/IIIa receptor antagonist) has been used to
      assess the contribution of the fibrinogen-platelet interaction to TEG parameters
      (in particular the maximum amplitude, MA). Modified TEG was compared with other
      investigations of platelet function to assess its sensitivity in both normal
      subjects and in patients with peripheral arterial disease (PAD), a condition
      associated with activated platelets. Blood was collected from eight healthy
      subjects and 12 PAD patients. Platelet function was measured by TEG, flow
      cytometry (using PAC-1, P-selectin, GP IIIa and GP Ib murine antibodies) and
      platelet aggregometry (spontaneous and ADP-induced) in the presence and absence
      of tirofiban (a GP IIb/IIIa receptor antagonist). TEG showed a statistically
      significant reduction in MA with tirofiban at 0.4 mg/L and an increase in k
      (kinetic time; which indicates how fast clot strength is increasing once clotting
      starts) at 0.2 and 0.4 mg/L of tirofiban in both healthy subjects and PAD
      patients. Flow cytometry showed a significant decrease in the PAC-1 binding index
      (at 0.2 mg/L). This finding was compatible with the significant reductions found
      in spontaneous and ADP-induced platelet aggregation. However, aggregometry and
      flow cytometry were more sensitive indicators of platelet inhibition than the TEG
      parameters. TEG does not provide a comprehensive or sensitive reflection of
      impaired platelet function. If TEG is used as an index of severely impaired
      platelet function, we recommend that the k parameter should be used as well as
      MA. TEG should be supplemented by other methods of platelet function assessment
      wherever possible.

PMID- 12812384
TI  - Antiphospholipid syndrome in obstetrics.
AB  - Antiphospholipid syndrome (APLS) in pregnancy is characterized by the presence of
      autoantibodies in association with recurrent fetal loss and severe complications
      such as preeclampsia, fetal growth retardation, or placental insufficiency. The
      most clinically important serologic markers are lupus anticoagulant,
      anticardiolipin antibodies, and recently anti-beta-2-glycoprotein 1 antibodies.
      At present, standardization does not exist and a definitive association between
      specific clinical manifestation and antibody level is not yet known. Experimental
      data gave evidence that passive transfer of antiphospholipid antibodies result in
      clinical manifestation of APLS, that is, fetal loss and thrombocytopenia.
      Treatment with heparin, aspirin, or intravenous immunoglobulins decreased the
      fetal loss rate. Treatment regimens in human are very difficult to interpret.
      Evidence from two prospective studies supported treatment with heparin and
      aspirin to improve pregnancy outcome. The risk of preeclampsia and placental
      insufficiency was substantial and occurred in 50% of patients. The general
      failure rate of heparin/aspirin treatment is approximately 30%. In such cases
      intravenous immunoglobulin in combination with heparin and aspirin has been used
      to treat APLS.

PMID- 12812385
TI  - Global fibrinolytic capacity in colorectal cancer: a new clue to occult
      fibrinolysis.
AB  - Hemostatic disorders in cancer patients range from asymptomatic laboratory
      changes to massive thromboembolism or hemorrhage. Routine laboratory tests often
      fail to identify patients at high risk for hemostatic complications. The
      postoperative risk of thromboembolic events in colorectal cancer was reported as
      approximately 2% to 5%. A new diagnostic test was used to assess global
      fibrinolytic activity, which may detect occult fibrinolysis or disseminated
      intravascular coagulation in patients with colorectal cancer. Twenty patients
      with colorectal cancer and 20 healthy control subjects were involved. Using
      standard silicated fibrin pellets and tissue plasminogen activator, the
      fibrinolytic capacity of the plasma samples was detected with the amount of D
      dimer produced before the reaction was stopped by adding aprotinin to the medium.
      Mean global fibrinolytic capacity was increased in patients before and after
      surgery when compared to controls (p = 0.002, p = 0.001, respectively). In
      conclusion, a hemostatic imbalance was detected toward primary fibrinolysis in
      the preoperative period and low-grade disseminated intravascular coagulation
      postoperatively.

PMID- 12812386
TI  - The prevalence of protein C, protein S, and antithrombin III deficiency in non
      APS/SLE Chinese adults with noncardiac cerebral ischemia.
AB  - Protein C (PC), protein S (PS), and antithrombin III (AT-III) are vital thrombin
      antagonists in circulation. However, the prevalence of these natural inhibitors
      for cerebral ischemia is barely mentioned in the Chinese population. The
      prevalence of PC, PS, and AT-III deficiency in Chinese adults with cerebral
      ischemia is reported. The study subjects were free of antiphospholipid antibody
      syndrome or systemic lupus erythematosus. Cardiac, liver, and renal function were
      normal. An overall rate of thrombophilia was 27%. PS deficiency was the most
      common disorder, followed by PC with PS and PC deficiency. There was only one
      patient with AT-III deficiency. No gender was specific for thrombophilia.
      However, PS deficiency was predilected in young adults. A positive correlation
      between PC and AT-III was achieved in patients with a normal PC activity but not
      PC deficiency. There was no correlation between AT-III or PS. The odds ratios of
      PC and PS were 5.29 and 2.86, respectively. Accordingly, an inability for
      thrombin antagonization by the PC/PS axis may relate to the occurrence of
      cerebral ischemia in the Chinese population. AT-III seems to display a minor role
      only.

PMID- 12812387
TI  - Ineffectiveness of measuring routine vital signs in adult inpatients with deep
      venous thrombosis.
AB  - The purpose of this study was to evaluate the benefit, if any, of routine
      monitoring of vital signs on clinical outcomes in hospitalized patients with deep
      venous thrombosis (DVT). One hundred forty-nine patients with DVT included in
      this study were categorized into two groups: those that underwent measurement of
      vital signs every 6 hours or those that had vital signs measured every 8 hours.
      Vital signs included pulse, blood pressure, respiratory rate, and temperature.
      Frequency of measurement of vital signs did not alter average length of star, for
      patients with every-4-hours measurement, this was 5.16 days and was not
      statistically significant from patients with every-8-hours measurement, who
      stayed an average of 4.85 days (p = 0.507). Similarly, more frequent vital sign
      evaluation did not result in a statistically significant difference in survival,
      progression of disease, nor did it predict the disposition of the patient. These
      results suggest that present frequency of measurement of vital signs is not cost
      or time effective because they do not result in a favorable outcome, length of
      stay, or disposition. The study further serves to highlight the need for an
      individualized assessment of vital sign measurement, because this will also lead
      to a more efficient allocation of hospital resources.

PMID- 12812388
TI  - Glanzmann's thrombasthenia proposed optimal management during surgery and
      delivery.
AB  - Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder of platelet
      function. Conventional management is by platelet transfusion, given before
      invasive interventions. Alloimmunization resulting in platelet refractoriness and
      an unpredictable response to platelet infusion have provided particular
      management difficulties in the past. More recently recombinant (r)VIIa
      (Novoseven) has a valuable role in the treatment of platelet function disorders.
      Treatment of a patient with GT during two pregnancies and spinal surgery is
      reported. An algorithm is presented to provide a structured and consistent
      approach to treatment.

PMID- 12812389
TI  - Hepatocyte growth factor: a possible mediator of heparin-induced osteoporosis?

PMID- 12812390
TI  - Short-term erythropoietin therapy does not increase plasma tissue factor and its
      inhibitor levels in hemodialysis patients.

PMID- 12812391
TI  - The development of ambulatory anesthesia and future challenges.
AB  - It is difficult to predict the future but foolish to ignore the past. The history
      of ambulatory anesthesia is one of many trends and societal or economic forces
      that have provided the impetus for the growth of the specialty. By understanding
      the events of the past one can have a greater understanding of the present and
      some insight into the possible trends of the future. Financial and societal
      forces will continue to drive the growth of ambulatory anesthesia. New
      technology, surgical techniques, and progress in anesthesiology will be financed
      and supported by society so long as ambulatory surgery continues to decrease the
      costs of health care. Although new technology may increase the direct costs of
      providing care in the operating room, the overall costs to society should be
      reduced by a decrease in lost productivity and individual suffering on the part
      of the patients. Regardless of future changes, the anesthesiologist must remain
      dedicated to the safety and comfort of the patient first and foremost. If that
      happens, then the future of ambulatory anesthesiology and surgery will continue
      to be bright.

PMID- 12812392
TI  - Preoperative screening for ambulatory patients.
AB  - Preoperative assessment of patients undergoing elective ambulatory procedures is
      constantly changing. Though the need for testing and outside consultation is
      decreasing, the challenges of creating systems that allow for timely review of
      information is growing. This article provides suggestions for addressing these
      issues during a period of increasing constraints in budgets and manpower.

PMID- 12812393
TI  - Challenging patients in an ambulatory setting.
AB  - An increasing number of surgical procedures are now performed on an ambulatory
      basis. This article reviews these conditions and defines the appropriate
      preoperative evaluation and perioperative management. Our goal is to define those
      patients who would benefit in having care in an inpatient setting or those who
      require more intensive medical evaluation or preparation prior to outpatient
      surgery.

PMID- 12812394
TI  - Inhalational techniques in ambulatory anesthesia.
AB  - In the current health care environment, anesthesia practitioners are frequently
      required to reevaluate their practice to be more efficient and cost-effective.
      Although IV induction with propofol and inhalational induction with sevoflurane
      are both suitable techniques for outpatients, patients prefer IV induction.
      Maintenance of anesthesia with the newer inhaled anesthetics (ie, desflurane and
      sevoflurane) provide for a rapid early recovery as compared with infusion of
      propofol (ie, TIVA), while allowing easy titratability of anesthetic depth.
      Titration of hypnotic sedatives using BIS monitoring may reduce the time to
      awakening and thereby may facilitate fast tracking (ie, bypassing the PACU) and
      reduce hospital stay. Inhalational anesthesia is associated with a higher
      incidence of PONV, but no differences have been demonstrated with respect to late
      recovery (eg, PACU stay and home readiness). Although clinical differences
      between desflurane and sevoflurane appear to be small, desflurane may be
      associated with faster emergence, particularly in elderly and morbidly obese
      patients. Balanced anesthesia with IV propofol induction and inhalation
      anesthesia with N2O for maintenance, and an LMA for airway management, may be an
      optimal technique for ambulatory surgery. Inhalational anesthesia may have an
      economic advantage over a TIVA technique.

PMID- 12812395
TI  - Intravenous techniques in ambulatory anesthesia.
AB  - The growing importance of ambulatory surgery during the past decade has led to
      the development of efficient anesthetic techniques in terms of quality and safety
      of anesthesia and recovery. In these challenging objectives, intravenous
      techniques have played an important role, as they provide safe, efficient, and
      cost-effective anesthesia in the ambulatory setting. Among the numerous
      intravenous drugs, propofol, with its fast and smooth onset of action, short
      duration of action, and low incidence of postoperative side effects appears to be
      the anesthetic of choice in this situation. The recent development of new
      techniques of administration (such as TCI, monitored anesthesia care, or patient
      controlled sedation) and monitoring (such as the BIS and the availability of "hit
      and run" drugs such as remifentanil) will optimize intraoperative conditions and
      recovery, thus allowing faster home readiness in the ambulatory setting.

PMID- 12812396
TI  - Regional anesthesia for outpatient surgery.
AB  - In summary, regional techniques offer significant advantages in the outpatient
      setting. They can avoid the side effects of nausea, vomiting, and pain that
      frequently delay discharge or cause admission. They can also provide prolonged
      analgesia as well as offer, with the use of continuous catheters, the promise of
      a pain-free perioperative period. The choice of drugs must be carefully adjusted,
      especially with neuraxial techniques. Despite frequently requiring some
      additional time at the outset, regional techniques have consistently been shown
      to provide competitive discharge times and costs when compared with general
      anesthesia. They deserve a prominent place in outpatient surgery.

PMID- 12812397
TI  - Current issues in pediatric ambulatory anesthesia.
AB  - This article summarizes current guidelines in pediatric ambulatory anesthesia and
      surgery. The reader is provided with our department's current outpatient
      guidelines at Children's Hospital of Philadelphia and the rationale behind them.
      Whenever possible, the differences in anesthetic management for the freestanding
      surgicenter will be discussed. Appropriate patient and procedure selection,
      preoperative assessment, intraoperative and postoperative considerations, and
      protocols for follow-up are discussed.

PMID- 12812398
TI  - Controversial issues in ambulatory anesthesia.
AB  - Many controversies surround ambulatory anesthesia, but this article concentrates
      on two major areas: monitoring devices and airway management. Being able to
      monitor the depth of anesthesia has been a long-term goal with the aim of
      avoiding awareness during surgery. As monitoring devices are developed, they are
      being used to reduce anesthetic delivery and reduce costs, possibly increasing
      the risk of awareness. Management of the airway has been revolutionized by the
      laryngeal mask, and this article reviews some controversial uses. Several other
      airway devices that have been developed and promoted as suitable alternatives
      also are evaluated.

PMID- 12812399
TI  - Effective analgesic modalities for ambulatory patients.
AB  - The introduction of government-mandated standards for pain management has focused
      our attention on postoperative pain. With the recent JACHO standards' for
      ambulatory surgery, it is imperative that all health care workers who care for
      these patients are familiar with appropriate pain management. Developments in our
      understanding of the pathophysiology of acute pain have further enhanced our
      ability to improve pain management for postoperative ambulatory patients. This
      has led to the concept of preventive analgesia (inhibition of physiological and
      pathological secondary inflammatory pain). Extensive work has shown that this is
      best achieved using a multimodel approach usually consisting of an NSAID, opioid,
      and local anesthetic. NMDA antagonists (ketamine, dextromethorphan) and alpha-2
      agnoists (clonodine) show potential supplements to further enhance pain
      management, especially if given preemptively. Nonpharmacological intervention
      such as cold therapy or acupuncture may also be considered. The armanentarium for
      effective pain management has improved substantially over the past few years. The
      challenge is for health care workers to implement these therapies to obtain
      optimum pain management in ambulatory surgical patients.

PMID- 12812400
TI  - Management of postoperative nausea and vomiting in ambulatory surgery.
AB  - The management of PONV has improved significantly over the years but remains a
      frequent occurrence in postoperative patients. Evaluation of individual patient
      risk and the consideration for prophylactic antiemetic in high-risk populations
      should reduce these unpleasant symptoms and help direct appropriate clinical
      strategies. Treatment following failure of prophylactic antiemetic therapy
      requires knowledge of previously used antiemetics and the time of their
      administration.

PMID- 12812401
TI  - Postoperative recovery and discharge.
AB  - Ambulatory surgery provides quality care that is cost-effective. The use of
      innovative surgical and anesthetic techniques will allow larger numbers of
      patients to take advantage of the benefits of undergoing an elective operation on
      an ambulatory basis. Anesthesiologists will be faced with more complex surgery,
      which will require careful selection and assessment of patients to ensure
      continuity of the excellent safety record of ambulatory anesthesia. Minor adverse
      events, such as pain and PONV, are still common. The occurrence of these minor
      adverse advents is now the major area of quality assessment and an area where
      improvement could be targeted. Fast tracking facilitates earlier discharge, but
      we must ensure this has benefit to the patient as speedy discharge may mask the
      true incidence of adverse minor symptoms. This can lead to patient
      dissatisfaction and a poor impression of ambulatory surgery.

PMID- 12812402
TI  - Scheduling of cases in an ambulatory center.
AB  - Perhaps the most important thing for an anesthesiologist and OR manager to
      understand is that there are different systems for OR allocation and case
      scheduling. We referred to them as Fixed Hours, Any Workday, and Reasonable Time.
      This understanding makes the OR management literature clear and applicable to all
      staff members. Most ambulatory centers handle cases on the workday chosen by the
      patient and surgeon but strive to do the work each day as efficiently as
      possible. Precisely how to make OR allocation and case scheduling decisions to
      achieve these objectives have been worked out. Studies show that case scheduling
      decisions to enhance OR efficiency are practiced in many facilities. In contrast,
      OR allocation decisions tend to be different than what OR managers do in
      practice. This means that it is important to apply the statistical methods for
      allocating OR time.

PMID- 12812403
TI  - Patient outcomes following ambulatory anesthesia.
AB  - As the number and type of surgeries performed in the ambulatory setting have
      increased, outcomes research has allowed for better analysis of the safety and
      efficacy of care given to patients. Though this once involved measures of
      clinical morbidity and mortality alone, researchers have begun to focus their
      attention beyond these end points and take into account patients' postoperative
      functional status and satisfaction as a way to assess the overall quality of
      patient care. Also key in this move to a more global assessment of health care
      interventions has been an increased focus on economic outcomes. As new anesthetic
      drugs and techniques continue to develop, outcomes research will continue to
      evolve in new directions, providing further information for improvements in
      patient care.

PMID- 12812404
TI  - Office-based anesthesia: an overview.
AB  - Office-based anesthesia, like other specific forms of anesthesia practice, has
      many unique attributes. Better work hours and a closer working relationship with
      surgeons and patients can provide the forum for a considerable amount of
      professional resonance. Moreover, the itinerant nature of the practice, the
      limited resources, and the need to innovate on the spur of the moment can make
      for variety and excitement. The gamut of anesthesia techniques, patient
      comorbidities, and surgeon expectations does not necessarily produce a facile
      experience, of course. But no specific anesthesia specialty or venue is devoid of
      challenge. While OBA is different from other types of anesthesia practice, this
      distinction does not necessarily make it superior or inferior. The political
      climate has improved, with more states acknowledging the status of OBS and OBA.
      This may force those OBA providers who routinely practice without regard to
      practical and appropriate industry standards out of business. AAAHC accreditation
      of an OBA practice may serve as a confidence-inspiring indication to patients
      that nationwide peer-reviewed standards are being met. However, everyone involved
      must recognize that accreditation is not a substitute for the sound application
      of clinical knowledge and expertise, as well as the collection and assessment of
      quality assurance data. It is inappropriate to view each OBS client as a
      minihospital. Although this may seem a simpler business model, the business and
      legal issues can be far more complex than those found in more traditional
      locales. A meld between business-person and clinician is becoming more a rule
      than an exception, and efforts to maintain and promote professional sovereignty
      will help forge continued growth of this unique form of anesthesiology practice.

PMID- 12812405
TI  - Headache case studies for the primary care physician.
AB  - In a given year, over 5% of persons in the United States seek medical care for
      headaches, most often seeing their primary care physician. The five cases here
      review diagnosis and treatment of migraine and other primary headaches,
      medication rebound headaches, and headaches in the elderly including temporal
      arteritis. Although headaches (along with dizziness and back pain) may be one of
      the least preferred diseases internists see, the increasing number of effective
      treatments may favorably change this opinion and result in better care for their
      patients.

PMID- 12812406
TI  - Dizziness.
AB  - There are several causes of dizziness, each of which requires a different form of
      management. Virtually all causes of dizziness can be treated with medication,
      diet, or physical therapy. This article discusses the most common causes of
      dizziness and management. Case examples are used extensively.

PMID- 12812407
TI  - Neck and low back pain.
AB  - These cases represent a sample of conditions that impact the spine and
      paraspinous structures. Central to establishing a correct diagnosis and the cost
      effective application of neurodiagnostic tests is a careful history and physical
      examination. The primary care physician is often the only physician to have a
      perception of the whole patient. The primary care physician is in an excellent
      position to initiate the evaluation of patients with spine symptoms and, where
      appropriate, monitor the treatment plans of consulting physicians.

PMID- 12812408
TI  - Entrapment and compressive neuropathies.
AB  - Entrapment and compressive neuropathies of the upper and lower extremities are
      frequently encountered disorders in the office. Certain clinical clues in the
      history and examination, along with electrodiagnostic testing and imaging
      studies, often suggest the correct diagnosis. Some of the more common
      neuropathies are discussed, along with suggestions regarding testing and
      treatment.

PMID- 12812409
TI  - Peripheral neuropathies in clinical practice.
AB  - Based on the history and physical examination, it is often possible to arrive at
      a relatively specific diagnosis of peripheral neuropathy. The clinical history
      and examination are often sufficient to create a more focused and appropriate
      laboratory evaluation, counseling for the patient as to long-term prognosis, and
      options for clinical management.

PMID- 12812410
TI  - Identifying and treating clinical subgroups of patients with epilepsy: a case
      review.
AB  - This article uses case reviews to illustrate key clinical features of several
      important epilepsy subgroups: newly diagnosed patients with epilepsy, women of
      childbearing age with seizures, elderly patients who develop epilepsy, patients
      with developmental disabilities, and patients with medication-resistant epilepsy.
      Characteristic clinical features for these patients (seizure types, ages of
      seizure onset, and treatment responses) guide clinical evaluation, treatment
      selections, and monitoring for medication side effects and seizures.

PMID- 12812411
TI  - Whole body [O-15]water pharmacokinetics measured in blood.
AB  - A simple pharmacokinetic model to explain the time course of [O-15] water in
      human whole blood after bolus injection is described. The model has been derived
      from measurements in twelve healthy volunteers who were measured repeatedly,
      resulting in 67 datasets, made in the context of PET blood flow studies. In
      contrast to traditional volume of distribution estimates of total body water
      (TBW) which rely on measurements after many hours, the model and data provide
      insights into the fast uptake components in the distribution of water in the
      body. Data fitting shows that the volume of distribution of fast exchanging
      tissues is 21 l. TBW was calculated to be 37 l. Monte Carlo simulation showed
      that the expected inaccuracy of determination of parameters due to unsystematic
      sources in the measurement data was around 5% for most parameters. Our data show
      that water extraction to tissue is somewhat higher than would be predicted from
      the tabulated values, probably because skeletal blood flow is sensitive to
      physiological status and environmental conditions. The study provides valuable
      reference data on the distribution and kinetics of water in man. Using the
      parameters and model from this study, reference input time-activity curves can be
      calculated, e.g. for the Monte Carlo study of error propagation in PET studies.

PMID- 12812412
TI  - In vivo electrical conductivity of hepatic tumours.
AB  - Knowledge of electrical tissue conductivity is necessary to determine deposition
      of electromagnetic energy and can further be used to diagnostically differentiate
      between normal and neoplastic tissue. We measured 17 rats with a total of 24
      tumours of the K12/TRb rat colon cancer cell line. In each animal we measured in
      vivo hepatic tumour and normal tissue conductivity at seven frequencies from 10
      Hz to 1 MHz, at different tumour stages between 6 and 12 weeks after induction.
      Conductivity of normal liver tissue was 1.26 +/- 0.15 mS cm(-1) at 10 Hz, and
      4.61 +/- 0.42 mS cm(-1) at 1 MHz. Conductivity of tumour was 2.69 +/- 0.91 mS cm(
      1) at 10 Hz, and 5.23 +/- 0.82 mS cm(-1) at 1 MHz. Conductivity was significantly
      different between normal and tumour tissue (p < 0.05). We determined the
      percentage of necrosis and fibrosis at the measurement site. We fitted the
      conductivity data to the Cole-Cole model. For the tumour data we determined
      Spearman's correlation coefficients between the Cole-Cole parameters and age,
      necrosis, fibrosis and tumour volume and found significant correlation between
      necrosis and the Cole-Cole parameters (p < 0.05). We conclude that necrosis
      within the tumour and the associated membrane breakdown is likely responsible for
      the observed change in conductivity.

PMID- 12812413
TI  - A simulation model of the oxygen alveolo-capillary exchange in normal and
      pathological conditions.
AB  - This paper presents a mathematical model of the oxygen alveolo-capillary exchange
      to provide the capillary oxygen partial pressure profile in normal and
      pathological conditions. In fact, a thickening of the blood-gas barrier, heavy
      exercise or a low oxygen partial pressure (PO2) in the alveolar space can reduce
      the O2 alveolo-capillary exchange. Since the reversible binding between
      haemoglobin and oxygen makes it impossible to determine the closed form for the
      mathematical description of the PO2 profile along the pulmonary capillaries, an
      approximate analytical solution of the capillary PO2 profile is proposed.
      Simulation results are compared with the capillary PO2 profile obtained by
      numerical integration and by a piecewise linear interpolation of the
      oxyhaemoglobin dissociation curve. Finally, the proposed model is evaluated in a
      large range of physiopathological diffusive conditions. The good fit to numerical
      solutions in all experimental conditions seems to represent a substantial
      improvement with respect to the approach based on a linear approximation of the
      oxyhaemoglobin dissociation curve, and makes this model a candidate to be
      incorporated into the integrated descriptions of the entire respiratory system,
      where the datum of primary interest is the value of end capillary PO2.

PMID- 12812414
TI  - Impedance spectroscopy for monitoring ischemic injury in the intestinal mucosa.
AB  - This work evaluates the feasibility of monitoring ischemic injury in the
      gastrointestinal mucosa by impedance spectroscopy, using a minimally invasive
      intestinal catheter. The disruption of the intestinal mucosa plays a key role in
      the evolution of shock and is the 'motor of multiple organ failure'. Different
      technologies have been developed to monitor mucosal perfusion, oxygenation and/or
      ischemia, but no practical method exists to assess tissue damage, which may be
      crucial for preventing multiple organ failure. The experimental protocol of this
      study relied on an isobaric model of hypovolemic shock in 16 anaesthetized
      rabbits assigned to three groups: sham (n = 6), ischemia (n = 5) and ischemia +
      reperfusion (n = 5). Complex impedance spectra were recorded in the range of 0.05
      to 300 kHz, with simultaneous measurements of tonometric pHi in the ileum every
      30 min for 4 h. Impedance spectra were reproducible, and those of tissue under
      prolonged ischemia were clearly differentiable from those of normally perfused
      tissue. The dynamic changes in impedance did not correlate directly with either
      tissue perfusion or pHi, but instead correlated well with the duration of
      ischemia. It is concluded that impedance spectroscopy does indeed measure changes
      in tissue injury, and could be a very useful tool to guide therapy of patients in
      shock.

PMID- 12812415
TI  - Low frequency electrical bioimpedance for the detection of inflammation and
      dysplasia in Barrett's oesophagus.
AB  - Biological tissues undergoing inflammation and dysplasia seem to exhibit changes
      in the intercellular space that can be sensed using low frequency electrical
      impedance methods. Basically, low frequency electric current flows through this
      space and its widening as well as the disruption of the tight junction decrease
      the resistance, facilitating current flow. The electrical changes accompanying
      structural changes from columnar tissue to adenocarcinoma in Barrett's
      metaplastic mucosa and gastric tissue are illustrated using resected tissue from
      32 patients. Two hundred and fifty-eight biopsies were analysed, correlating
      their electrical resistivity (R) at 9.6 kHz and their histopathological
      interpretation. Compared to non-inflamed non-dysplastic columnar tissue (R = 4.9
      ohms m), the results suggest a small but statistically significant decrease of
      electrical impedance in columnar tissue showing inflammation (R = 4.2 ohms m, p =
      0.016) and a larger decrease when dysplasia is present (R = 3.4 ohms m, p =
      0.040). If this method is validated further, this technique could be used to
      obtain guided biopsies from patients undergoing surveillance programmes for
      Barrett's oesophagus. We aim to refine this technique using a new system with
      lower frequencies and, possibly, in vitro (cultured cells) and in vivo (rats)
      models of Barrett's oesophagus.

PMID- 12812416
TI  - Age-related changes in the characteristics of the photoplethysmographic pulse
      shape at various body sites.
AB  - It is accepted that older subjects have increasing arterial stiffness resulting
      in changes in the propagation of the pulse to the periphery, and thereby
      influencing the peripheral pulse timing and shape characteristics. However, this
      age association with pulse shape is less clear in younger subjects and for
      different peripheral measurement sites. The aim of this study was to determine
      the association between age and changes in pulse shape characteristics at the
      ears, fingers and toes. Photoplethysmography pulse waveforms were recorded non
      invasively from the right and left sides at the ears, index fingers and great
      toes of 116 normal healthy human subjects. Their median age was 41 years (range
      13-72) allowing four distinct age groups to be considered (subjects younger than
      30 years, 30-39 years, 40-49 years and 50 years of age or older). Normalized ear,
      finger and toe pulse shapes were calculated, for the whole subject group, and for
      the subjects within each age group. The differences in shape, relative to the
      oldest group, were also calculated for two distinct regions of interest: the
      systolic rising edge and the dicrotic notch of the pulse. Subtle, gradual and
      significant changes in the pulse shape were found at all sites with overall
      elongation of the systolic rising edge (p < 0.05) and damping of the dicrotic
      notch (p < 0.05) with age. The overall age-related changes in multi-site PPG
      pulse shape characteristics at the ear, finger and toe sites have been
      demonstrated and quantified. Age-matched normal ranges must be considered when
      evaluating pulses from patients with possible vascular disease.

PMID- 12812417
TI  - Evaluation of the forearm EMG signal features for the control of a prosthetic
      hand.
AB  - The purpose of this research is to select the best features to have a high rate
      of motion classification for controlling an artificial hand. Here, 19 EMG signal
      features have been taken into account. Some of the features suggested in this
      study include combining wavelet transform with other signal processing
      techniques. An assessment is performed with respect to three points of view: (i)
      classification of motions, (ii) noise tolerance and (iii) calculation complexity.
      The energy of wavelet coefficients of EMG signals in nine scales, and the
      cepstrum coefficients were found to produce the best features in these views.

PMID- 12812418
TI  - An instrument to measure the heat convection coefficient on the endocardial
      surface.
AB  - This work describes the fundamentals and calibration procedure of an instrument
      for in vivo evaluation of the heat convection coefficient between the endocardium
      and the circulating blood flow. The instrument is to be used immediately before
      radio-frequency cardiac ablation is performed. Thus, this instrument provides
      researchers with a valuable parameter to predict lesion size to be achieved by
      the procedure. The probe is a thermistor mounted in a Swan-Ganz catheter, and it
      is driven by a constant-temperature anemometer circuit. A 1D model of the sensor
      behaviour in a convective medium, the calibration procedure and the apparatus are
      explained in detail. Finally, a performance analysis of the instrument in the
      range of 200-3500 W m(-2) K(-1) shows that the average absolute error of full
      scale is 7.4%.

PMID- 12812419
TI  - Measurement of gastric contraction activity in dogs by means of AC
      biosusceptometry.
AB  - The mechanical nature of gastric contraction activity (GCA) plays an important
      role in gastrointestinal motility. The aim of this study was to detect GCA in
      anaesthetized dogs, using simultaneously the techniques of AC biosusceptometry
      (ACB) and manometry, analysing the characteristics of frequency and amplitude
      (motility index) of GCA, modified by drugs such as prostigmine and N-butyl
      scopolamine. The ACB method is based on a differential transformer of magnetic
      flux and the magnetic tracer works as a changeable external nucleus. This
      magnetic tracer causes a modification in the magnetic flux, which is detected by
      the coils. The results obtained from the ACB showed a performance comparable to
      the manometry in measuring the modifications in the frequency and amplitude of
      the GCA. We concluded that this ACB technique, non-invasive and free of ionizing
      radiation, is an option for evaluating GCA and can be employed in future clinical
      studies.

PMID- 12812420
TI  - Predicting clinical ischaemia during awake carotid endarterectomy: use of the
      SJVO2 probe as a guide to selective shunting.
AB  - Stroke is a major cause of disability within the western world. About 20% of
      strokes are a consequence of atheromatous narrowing of the origin of the internal
      carotid artery. Carotid endarterectomy has been shown to be an effective
      treatment for those with symptomatic and severe stenosis, provided the risk of
      death and peri-operative stroke is less than 7%. The aim of this study was to
      investigate the clinical value of jugular venous oxygen saturation (SJVO2)
      monitoring in identifying patients who develop cerebral ischaemia whilst
      undergoing an awake carotid endarterectomy by comparison with a simple
      neurological assessment. Each patient underwent a standard awake carotid
      endarterectomy. Peri-operatively a SJVO2 catheter was inserted, and the jugular
      oxygen saturation was correlated with the presence or absence of cerebral
      ischaemia. Data from 34 patients were analysed using time-series plots and by
      calculating a receiver operator characteristic (ROC) curve. The optimal
      sensitivity and specificity for this technique were found to be 1.0 and 0.8,
      respectively, when a 25% change in SJVO2 was used as a threshold. Although a
      small observational study, we have shown that percentage change in SJVO2
      correlates well with the development of clinically apparent cerebral ischaemia.
      This technique may improve the safety of carotid endarterectomy under general
      anaesthesia when used with other more established monitoring methods.

PMID- 12812421
TI  - In vitro validation of an ultrasonic flowmeter in order to measure the functional
      residual capacity in newborns.
AB  - Ultrasonic transit-time airflow meters (UFM) allow simultaneous measurements of
      volume flow V'(t) and molar mass MM(t) of the breathing gas in the mainstream.
      Consequently, by using a suitable tracer gas the functional residual capacity
      (FRC) of the lungs can be measured by a gas wash-in/wash-out technique. The aim
      of this study was to investigate the in vitro accuracy of a multiple-breath wash
      in/wash-out technique for FRC measurements using 4% sulphur hexafluoride (SF6) in
      air. V'(t) and MM(t) were measured with a Spiroson SCIENTIFIC flowmeter (ECO
      Medics, CH) with 1.3 ml dead space. Linearity of airflow and MM were tested using
      different tidal volumes (V(T)) and breathing gases with different O2 and SF6
      concentrations. To determine the accuracy of FRC measurements SF6 wash-in and
      wash-out curves from four mechanical lung models (FRC of 22, 53, 102 and 153 ml)
      were evaluated by the Spiroson. For each model five measurements were performed
      with a physiological V(T)/FRC ratio of 0.3 and constant respiratory rate of 30
      min(-1). The error of measured V(T) (range 4-60 ml) was <2.5%. There was a strong
      correlation between the measured and calculated MM of different breathing gases
      (r = 0.989), and the measuring accuracy was better than 1%. The measured FRC of
      the four models were 20.3, 49.7, 104.3 and 153.4 ml with a coefficient of
      variation of 16.5%, 4.5%, 4.9% and 3%. Accordingly, for FRC <100 ml the in vitro
      accuracy was better than 8% and for FRC >100 ml better than 2.5%. The
      determination of FRC by MM measurements using the UFM is a simple and cost
      effective alternative to conventionally used gas analysers with an acceptable
      accuracy for many clinical purposes.

PMID- 12812422
TI  - Variability of time-domain indices of dynamic cerebral autoregulation.
AB  - The intra- and inter-subject variabilities of the cerebral dynamic autoregulatory
      index (ARI) were studied in a group of 14 healthy subjects aged 23-51 years. An
      alternative index, derived from autoregressive-moving average (ARMA) modelling of
      the arterial blood pressure (ABP)-cerebral blood flow velocity (CBFV) dynamic
      relationship, named ARMA-ARI, is also proposed. The susceptibility of both
      indices to physiological sources of variability was studied by performing
      measurements during spontaneous respiration (SR), and controlled breathing at 6,
      10 and 15 breaths min(-1). ABP was measured non-invasively (Finapres), CBFV was
      recorded with Doppler ultrasound in both middle cerebral arteries and end-tidal
      CO2 (EtCO2) was estimated with an infrared capnograph. ARI and ARMA-ARI were
      calculated as a summary measure for the whole of each recording period, and also
      continuously, using a 60 s moving data window. Respiration did not have an effect
      on either of these indices, despite significant, but relatively small, reductions
      in EtCO2 at 10 and 15 bpm, compared to SR. Very significant differences were
      observed between ARI and ARMA-ARI in relation to their stability, variability and
      sensitivity to discriminate between subjects. For continuous estimates the
      coefficient of variation of ARI was 30 +/- 21% compared to 15 +/- 8% for ARMA-ARI
      (p < 0.000). The cumulative probability distributions were also significantly
      different for the two indices for each of the respiratory manoeuvres. The greater
      stability and reduced variability of ARMA-ARI, in relation to the classic ARI,
      suggest that the former should be used in future studies of dynamic
      autoregulation, mainly in situations where an improved temporal resolution might
      be required, such as the investigation of vaso-vagal syncope or the physiology of
      exercise.

PMID- 12812423
TI  - Dielectric constant of skin and subcutaneous fat to assess fluid changes after
      cardiac surgery.
AB  - The ability to objectively determine the degree of tissue edema and to monitor on
      line fluid balance in critically ill patients would be a clinical benefit. In
      this prospective descriptive trial, we evaluated a new noninvasive method-
      dielectric constant of skin and subcutaneous fat (SSF)--in assessing fluid
      balance during cardiac surgery. The dielectric constant at the applied high
      radiofrequency is a direct measure of tissue water content. Twenty-nine patients
      with elective cardiac surgery participated in the study. Dielectric constants on
      forearm, thigh and abdomen were measured before surgery, within 1 h after surgery
      and in the first, second, third and fourth postoperative morning. At the same
      time the patients were weighed, except immediately after the operation and the
      first postoperative day when fluid balances were calculated. A statistically
      significant correlation (r = 0.60, p < 0.01) was found between the increase of
      the dielectric constant of SSF and weight gain of the patients from the baseline
      to the second postoperative morning. From the second to the fourth postoperative
      day when the patients were losing the weight, a statistical significant
      correlation between the dielectric constant and weight loss was not found. The
      results suggest that the measurement of the dielectric constant is a promising
      new method in assessing the fluid status of operated patients during the time the
      patients cannot be weighed.

PMID- 12812424
TI  - A new direct method for reconstructing isotropic conductivities in the plane.
AB  - In this paper we describe a new, direct and mathematically exact method for the
      reconstruction of the isotropic conductivity in a plane body from static electric
      measurements on the boundary of the body. The method is inspired by a uniqueness
      proof for the inverse conductivity problem due to Brown-Uhlmann and covers
      conductivities having essentially one derivative. Moreover, we give a numerical
      implementation of the algorithm and test the performance on a simple, synthetic
      example.

PMID- 12812425
TI  - Distinguishability of inhomogeneities using planar electrode arrays and different
      patterns of applied excitation.
AB  - Electrical impedance tomography (EIT) is a non-invasive technique used to image
      the electrical conductivity and permittivity within a body from measurements
      taken on the body surface. Four methods are being investigated for breast cancer
      diagnosis by EIT today: Single voltage source, single current source and multiple
      current sources with a fixed pre-determined 'canonical' pattern of currents and
      an adaptively determined 'optimal' pattern of currents. To determine which of
      these four methods might yield the best distinguishability using planar electrode
      arrays for breast cancer detection, we placed electrode arrays on a saline tank
      and used each excitation pattern to detect a conducting target placed at the
      centre of a flat electrode array in two geometries: mammography geometry and
      single probe geometry. The result was that the multiple current sources method
      had higher distinguishability than either the SCS or the SVS method. In both
      these electrode geometries, the optimal current pattern had higher
      distinguishability than the other patterns at all distances.

PMID- 12812426
TI  - Anisotropic conductivities that cannot be detected by EIT.
AB  - We construct anisotropic conductivities in dimension 3 that give rise to the same
      voltage and current measurements at the boundary of a body as a homogeneous
      isotropic conductivity. These conductivities are non-zero, but degenerate close
      to a surface inside the body.

PMID- 12812427
TI  - A novel data calibration scheme for electrical impedance tomography.
AB  - In electrical impedance tomography surface measurements of voltages and currents
      are recorded and the image reconstruction algorithm uses this set of boundary
      data to estimate internal electrical properties of the region under
      investigation. Therefore correct and accurate modelling of the current and
      voltage distributions (forward model) is an essential part of any reconstruction
      method. In this paper, we explored the root cause of a boundary layer effect in
      the reconstructed conductivity map and found it to be an artefact arising from 2D
      to 3D data-model mismatch within the imaging algorithm. We propose a data
      calibration scheme that improves the reconstruction results by removing these
      boundary or edge effects. We present both two-dimensional and three-dimensional
      images for agar phantoms using this data calibration scheme which are markedly
      better than their counterparts recovered when the measurement data are not
      calibrated with the procedure outlined herein.

PMID- 12812428
TI  - Direct estimation of Cole parameters in multifrequency EIT using a regularized
      Gauss-Newton method.
AB  - A major drawback of electrical impedance tomography is the poor quality of the
      conductivity images, i.e., the low spatial resolution as well as large errors in
      the reconstructed conductivity values. The main reason is the necessity for
      regularization of the ill-conditioned inverse problem which results in excessive
      spatial low-pass filtering. A novel regularization method (SMORR (spectral
      modelling regularized reconstructor)) is proposed, which is based on the
      inclusion of spectral a priori information in the form of appropriate tissue
      models (e.g. Cole models). This approach reduces the ill-posedness of the inverse
      problem, when multifrequency data are available. An additional advantage is the
      direct reconstruction of the (physiological) tissue parameters of interest
      instead of the conductivities. SMORR was compared with posterior fitting of a
      Cole model to the conductivity spectra obtained with a classical iterative
      reconstruction scheme at various frequencies. SMORR performed significantly
      better than the reference method concerning robustness against noise in the data.

PMID- 12812429
TI  - The application of the generalized vector sample pattern matching method for EIT
      image reconstruction.
AB  - This paper presents a new application of a generalized vector sample pattern
      matching (GVSPM) method for image reconstruction of conductivity changes in
      electrical impedance tomography. GVSPM is an iterative method for linear inverse
      problems. The key concept of the GVSPM is that the objective function is defined
      in terms of an angular component between the inner product of the known vector
      and solution of a system of equations. Comparisons are presented between images
      of simulated and experimental data, reconstructed using truncated singular value
      decomposition and GVSPM. In both cases, a normalized sensitivity matrix is
      constructed using the finite volume method to solve the forward problem.

PMID- 12812430
TI  - Evaluation of an EIT reconstruction algorithm using finite difference human
      thorax models as phantoms.
AB  - A finite difference model of the human thorax with 113,400 control volumes
      (nodes) based on ECG gated MRI images was used to evaluate the Sheffield DAS-01P
      EIT system. Sixteen simulated electrode positions equally spaced around the
      thorax model at approximately the fourth intercostals space level were selected.
      Pairs of adjacent positions were excited sequentially by injecting current in a
      manner similar to that used by the Sheffield DAS-01P EIT system. The resulting
      voltages on the non-excited electrode positions were calculated and used to
      reconstruct the image using the Sheffield filtered back projection algorithm. By
      changing the resistivities of the lungs, the ventricles and the atria over a
      range of 1% to 40%, the resulting changes in the images were quantified by
      measuring the average resistivity change over a region defined automatically by
      two thresholds, 40% or 80% of the average of the first four pixels with the
      largest change. The results show that the changes observed in the images are
      consistently less than the changes in the model, but changed in a nearly linear
      manner as a function of resistivity in the model. For 40% resistivity changes in
      the model for right lung, right ventricle and right atrium, the observed
      resistivity changes in the region of interest (ROI, defined by the 80% threshold)
      of the images are 32% for the right lung, 11% for the right ventricle and 5.5%
      for the right atrium, which suggests strong volume dependence of EIT imaging. The
      effect of structural (size) change between end diastole and end systole was also
      studied, which showed large resistivity changes caused in the heart region of the
      constructed image. The study demonstrates that the Sheffield DAS-01P EIT
      reconstruction algorithm tracks the change occurring in the lungs most closely
      and with proper scaling may be used to observe physiological changes.

PMID- 12812431
TI  - Electrical impedance tomography spectroscopy (EITS) for human head imaging.
AB  - Electrical impedance tomography (EIT) is a recently developed medical imaging
      method which has practical advantages for imaging brain function as it is
      inexpensive, rapid and portable. Its principal use in validated human studies to
      date has been to image changes in impedance at a single excitation frequency over
      time, but there are potential applications where it is desirable to obtain images
      from a single point in time, which could be achieved by imaging over multiple
      frequencies. We describe a novel multifrequency EIT design which provides up to
      64 electrodes for imaging in the head. This was achieved by adding a multiplexer
      to a single channel of an existing system, the Sheffield Mark 3.5. This provides
      a flexible protocol for addressing up to 64 electrodes but CMRR decreases from 90
      dB to 80 dB and analogue amplifier bandwidth from > 1.6 MHz to 0.8 MHz. This did
      not significantly affect performance, as cylinders of banana, 10% of the diameter
      of a saline filled spherical tank, could be visualized with frequency referenced
      imaging. The design appears to have been an acceptable compromise between
      practicality and performance and will now be employed in clinical trials of
      multifrequency EIT in stroke, epilepsy and neonatal brain injury.

PMID- 12812432
TI  - Electrical impedance tomography to measure pulmonary perfusion: is the
      reproducibility high enough for clinical practice?
AB  - A possible clinical application of electrical impedance tomography (EIT) might be
      to monitor changes in the pulmonary circulation, provided the reproducibility of
      the EIT measurement is adequate. The purpose of this study was threefold: the
      intra- and inter-investigator variability of repeated measurements was
      investigated. Three different regions of interest (ROI) were analysed to assess
      the optimal ROI. Twenty-four healthy subjects and six patients were included. The
      Sheffield applied potential tomograph (DAS-01P, IBEES, Sheffield, UK) was used.
      Electrodes were attached by investigator A, and duplicate EIT measurements were
      performed. After detachment and 45 min of rest, the protocol was repeated by
      another investigator B, and afterwards by the initial investigator A. Three ROIs
      were analysed: whole circle, 'inner half circle' and contour. The mean difference
      in impedance changes between observers is presented in arbitrary units (AU) +/-
      SD. Finally, the influence of age, body composition and sex on the EIT result was
      examined. For the contour ROI, the mean difference for the intra-investigator
      situation was -1.44 x 10(-2) +/- 18.45 x 10(-2) AU (-0.7 +/- 9.0%), and was 5.46
      x 10(-2) +/- 21.66 x 10(-2) AU (2.7 +/- 10.8%) for the inter-investigator
      situation. The coefficient of reproducibility of the intra- and inter
      investigator reproducibility varied between 0.89 and 0.97 for all ROIs (P <
      0.0001). There is a relation between impedance change and age (correlation
      coefficient r = -0.63, P < 0.01 for contour ROI), and between impedance change
      and body mass index (BMI) (r = -0.53, P < 0.05). We found a significant
      difference in mean impedance change between groups of males and females. In
      conclusion, EIT results are highly reproducible when performed by the same
      investigator as well as by two different investigators.

PMID- 12812433
TI  - Circuit for the measurement of small phase delays in MIT.
AB  - A single-channel MIT measuring system for obtaining phase delays is given. The
      circuit, which is described in detail, uses a high-frequency analogue multiplier
      to measure the phase difference between the signal and a reference signal. The
      noise in the phase measurement is approximately 1.5 millidegree when the time
      constant of measuring is 0.1 s, and the drift over about 1 day is approximately
      10 millidegree.

PMID- 12812434
TI  - Current source design for electrical impedance tomography.
AB  - Questions regarding the feasibility of using electrical impedance tomography
      (EIT) to detect breast cancer may be answered by building a sufficiently precise
      multiple frequency EIT instrument. Current sources are desirable for this
      application, yet no current source designs have been reported that have the
      required precision at the multiple frequencies needed. We have designed an EIT
      current source using an enhanced Howland topology in parallel with a generalized
      impedance converter (GIC). This combination allows for nearly independent
      adjustment of output resistance and output capacitance, resulting in simulated
      output impedances in excess of 2 Gohms between 100 Hz and 1 MHz. In this paper,
      the theoretical operation of this current source is explained, and experimental
      results demonstrate the feasibility of creating a high precision, multiple
      frequency, capacitance compensated current source for EIT applications.

PMID- 12812435
TI  - Stand-off electrode (SoE): a new method for improving the sensitivity
      distribution of a tetrapolar probe.
AB  - Tetrapolar probes have been widely used for measuring the impedance spectra of
      tissues. However, the non-uniform sensitivity distribution of these probes limits
      the ability to identify conductivity changes in tissue. This paper presents a
      novel method for improving the sensitivity distribution beneath a tetrapolar
      probe. The method consists of placing a hydrogel layer between the probe and the
      tissue in order to make the sensitivity positive everywhere within the tissue.
      Theoretical and measured sensitivity distributions are compared. A good agreement
      between theoretical and measured data from an electrolytic tank was obtained with
      a maximum error of 1.3%. In vivo forearm measurements showed that the use of a
      conductive layer does enable tissue conductivity spectra to be determined. A
      smaller variation between subjects was obtained when using the stand-off. It was
      not possible to assess the absolute accuracy of the method due to the absence of
      a 'gold standard' for the measurement of tissue conductivity spectra.

PMID- 12812436
TI  - A comparison of headnet electrode arrays for electrical impedance tomography of
      the human head.
AB  - Three types of commercially available headnet electrode arrays, designed for use
      in EEG, and conventional EEG Ag/AgCl cup electrodes were tested on human
      subjects, and a realistic, saline-filled head-shaped tank was prepared with
      vegetable skin to simulate human skin in order to determine the optimum electrode
      system for electrical impedance tomography (EIT) of the human head. Impedance
      changes during EIT acquisition were produced in healthy volunteers during a
      finger-thumb apposition task and in tanks by the insertion of a Perspex rod.
      Signal-to-baseline noise, measured from raw EIT data, was 2.3 +/- 0.3 and 2.3 +/-
      0.2 for the human and tank data, respectively. In both the human and tank
      experiments, a commercial hydrogel elasticated electrode headnet produced the
      least amount of baseline noise, and was the only headnet in the human data with
      noise levels acceptable for EIT imaging. Image quality measured in the tank was
      similar for most of the headnets tested, except that the EEG electrodes produced
      a higher positional error and electrodes in a geodesic elasticated net produced
      images with worse subjective image quality. Overall, the hydrogel elasticated
      headnet was judged to be the most suitable for human neuroimaging with EIT.

PMID- 12812437
TI  - Numerical solution of the general 3D eddy current problem for magnetic induction
      tomography (spectroscopy).
AB  - Magnetic induction tomography (MIT) is used for reconstructing the changes of the
      conductivity in a target object using alternating magnetic fields. Applications
      include, for example, the non-invasive monitoring of oedema in the human brain. A
      powerful software package has been developed which makes it possible to generate
      a finite element (FE) model of complex structures and to calculate the eddy
      currents in the object under investigation. To validate our software a model of a
      previously published experimental arrangement was generated. The model consists
      of a coaxial coil system and a conducting sphere which is moved perpendicular to
      the coil axis (a) in an empty space and (b) in a saline-filled cylindrical tank.
      The agreement of the measured and simulated data is very good when taking into
      consideration the systematic measurement errors in case (b). Thus the
      applicability of the simulation algorithm for two-compartment systems has been
      demonstrated even in the case of low conductivities and weak contrast. This can
      be considered an important step towards the solution of the inverse problem of
      MIT.

PMID- 12812438
TI  - Magnetic induction tomography: phase versus vector-voltmeter measurement
      techniques.
AB  - In magnetic induction tomography (MIT) the in-quadrature component, and hence the
      phase, of the received signal contains information about the conductivity of the
      tissue. The quality of imaging will depend on the precision with which phase can
      be measured. Preliminary studies suggest that a precision of 10 m degrees may be
      required for a practical biomedical MIT system operating at 10 MHz. This paper
      describes the results of measurements carried out with a 16-channel,
      downconverting, 10 MHz, MIT system utilizing two types of data extraction
      techniques: direct-phase measurement and measurement of the in-phase and in
      quadrature components of the signal with a vector voltmeter. The basic precision
      provided by each technique was 50 m degrees, with thermal drift representing the
      major limiting factor. Preliminary measurements of average conductivity and
      permittivity for a human thigh in vivo are given.

PMID- 12812439
TI  - Reconstruction of current density distributions in axially symmetric cylindrical
      sections using one component of magnetic flux density: computer simulation study.
AB  - In magnetic resonance current density imaging (MRCDI), we inject current into a
      subject through surface electrodes and measure the induced magnetic flux density
      B inside the subject using an MRI scanner. Once we have obtained all three
      components of B, we can reconstruct the internal current density distribution J =
      inverted triangle x B/mu0). This technique, however, requires subject rotation
      since the MRI scanner can measure only one component of B that is parallel to the
      direction of its main magnetic field. In this paper, under the assumption that
      the out-of-plane current density Jz is negligible in an imaging slice belonging
      to the xy-plane, we developed an imaging technique of current density
      distributions using only Bz, the z-component of B. The technique described in
      this paper does not require a subject rotation but the quality of reconstructed
      images depends on the amount of out-of-plane current density Jz. From numerical
      simulations, we found that the new algorithm could be applied to subjects such as
      human limbs using longitudinal electrodes.

PMID- 12812440
TI  - Static resistivity image of a cubic saline phantom in magnetic resonance
      electrical impedance tomography (MREIT).
AB  - In magnetic resonance electrical impedance tomography (MREIT) we inject currents
      through electrodes placed on the surface of a subject and try to reconstruct
      cross-sectional resistivity (or conductivity) images using internal magnetic flux
      density as well as boundary voltage measurements. In this paper we present a
      static resistivity image of a cubic saline phantom (50 x 50 x 50 mm3) containing
      a cylindrical sausage object with an average resistivity value of 123.7 ohms cm.
      Our current MREIT system is based on an experimental 0.3 T MRI scanner and a
      current injection apparatus. We captured MR phase images of the phantom while
      injecting currents of 28 mA through two pairs of surface electrodes. We computed
      current density images from magnetic flux density images that are proportional to
      the MR phase images. From the current density images and boundary voltage data we
      reconstructed a cross-sectional resistivity image within a central region of 38.5
      x 38.5 mm2 at the middle of the phantom using the J-substitution algorithm. The
      spatial resolution of the reconstructed image was 64 x 64 and the reconstructed
      average resistivity of the sausage was 117.7 ohms cm. Even though the error in
      the reconstructed average resistivity value was small, the relative L2-error of
      the reconstructed image was 25.5% due to the noise in measured MR phase images.
      We expect improvements in the accuracy by utilizing an MRI scanner with higher
      SNR and increasing the size of voxels scarifying the spatial resolution.

PMID- 12812441
TI  - Uniqueness and reconstruction in magnetic resonance-electrical impedance
      tomography (MR-EIT).
AB  - Magnetic resonance-electrical impedance tomography (MR-EIT) was first proposed in
      1992. Since then various reconstruction algorithms have been suggested and
      applied. These algorithms use peripheral voltage measurements and internal
      current density measurements in different combinations. In this study the problem
      of MR-EIT is treated as a hyperbolic system of first-order partial differential
      equations, and three numerical methods are proposed for its solution. This
      approach is not utilized in any of the algorithms proposed earlier. The numerical
      solution methods are integration along equipotential surfaces (method of
      characteristics), integration on a Cartesian grid, and inversion of a system
      matrix derived by a finite difference formulation. It is shown that if some
      uniqueness conditions are satisfied, then using at least two injected current
      patterns, resistivity can be reconstructed apart from a multiplicative constant.
      This constant can then be identified using a single voltage measurement. The
      methods proposed are direct, non-iterative, and valid and feasible for 3D
      reconstructions. They can also be used to easily obtain slice and field-of-view
      images from a 3D object. 2D simulations are made to illustrate the performance of
      the algorithms.

PMID- 12812442
TI  - Modelling of epithelial tissue impedance measured using three different designs
      of probe.
AB  - Impedance measurement is a promising technique for detecting pre-malignant
      changes in epithelial tissue. This paper considers how the design of the
      impedance probe affects the ability to discriminate between tissue types. To do
      this, finite element models of the electrical properties of squamous and
      glandular columnar epithelia have been used. The glandular tissue model is
      described here for the first time. Glandular mucosa is found in many regions of
      the gastrointestinal tract, such as the stomach and intestine, and has a large
      effective surface area. Firstly, the electrical properties of a small section of
      gland, with epithelial cells and supportive tissue, are determined. These
      properties are then used to build up a three-dimensional model of a whole section
      of mucosa containing many thousands of glands. Measurements using different types
      of impedance probe were simulated by applying different boundary conditions to
      the models. Transepithelial impedance, and tetrapolar measurement with a probe
      placed on the tissue surface have been modelled. In the latter case, the
      impedance can be affected by conductive fluid, such as mucus, on the tissue
      surface. This effect has been investigated, and a new design of probe, which uses
      a guard electrode to counteract this potential source of variability, is
      proposed.

PMID- 12812443
TI  - Tumour tissue monitoring during photodynamic and hyperthermic treatment using
      bioimpedance spectroscopy.
AB  - Electrical bioimpedance spectroscopy is a fast and relatively easily applicable
      method for tissue characterization. In the frequency range up to 10 MHz, current
      conduction through tissue is mainly determined by tissue structure, i.e. the
      extra- and intra-cellular compartments and the insulating cell membranes.
      Therefore, changes in the extra- and intra-cellular fluid volumes are reflected
      in the impedance spectra. Investigations of tumours (DS sarcoma, implanted on the
      hind foot dorsum of rats) during treatment with localized hyperthermia (HT),
      photodynamic therapy (PDT) and the combination of these two components were
      carried out using impedance spectroscopy in the frequency range of 37 Hz to 3.7
      MHz. Data collected reveal totally different, but characteristic, behaviour
      patterns for the three treatments. HT caused a slow increase in conductance at
      high frequencies (G(HF)) and in the extracellular space index (ECSI), indicating
      an increase in extracellular fluid volume and in total fluid content. With PDT,
      G(HF) increased immediately upon commencement of irradiation and was accompanied
      by a distinct decrease in ECSI, indicating the development of a pronounced
      intracellular oedema.

PMID- 12812444
TI  - All about MAX: a male adult voxel phantom for Monte Carlo calculations in
      radiation protection dosimetry.
AB  - The MAX (Male Adult voXel) phantom has been developed from existing segmented
      images of a male adult body, in order to achieve a representation as close as
      possible to the anatomical properties of the reference adult male specified by
      the ICRP. The study describes the adjustments of the soft-tissue organ masses, a
      new dosimetric model for the skin, a new model for skeletal dosimetry and a
      computational exposure model based on coupling the MAX phantom with the EGS4
      Monte Carlo code. Conversion coefficients between equivalent dose to the red bone
      marrow as well as effective MAX dose and air-kerma free in air for external
      photon irradiation from the front and from the back, respectively, are presented
      and compared with similar data from other human phantoms.

PMID- 12812445
TI  - Calculations of electron fluence correction factors using the Monte Carlo code
      PENELOPE.
AB  - In electron-beam dosimetry, plastic phantom materials may be used instead of
      water for the determination of absorbed dose to water. A correction factor
      phi(water)plastic is then needed for converting the electron fluence in the
      plastic phantom to the fluence at an equivalent depth in water. The recommended
      values for this factor given by AAPM TG-25 (1991 Med. Phys. 18 73-109) and the
      IAEA protocols TRS-381 (1997) and TRS-398 (2000) disagree, in particular at large
      depths. Calculations of the electron fluence have been done, using the Monte
      Carlo code PENELOPE, in semi-infinite phantoms of water and common plastic
      materials (PMMA, clear polystyrene, A-150, polyethylene, Plastic water and Solid
      water (WT1)). The simulations have been carried out for monoenergetic electron
      beams of 6, 10 and 20 MeV, as well as for a realistic clinical beam. The
      simulated fluence correction factors differ from the values in the AAPM and IAEA
      recommendations by up to 2%, and are in better agreement with factors obtained by
      Ding et al (1997 Med. Phys. 24 161-76) using EGS4. Our Monte Carlo calculations
      are also in good accordance with phi(water)plastic values measured by using an
      almost perturbation-free ion chamber. The important interdependence between depth
      and fluence-scaling corrections for plastic phantoms is discussed. Discrepancies
      between the measured and the recommended values of phi(water)plastic may then be
      explained considering the different depth-scaling rules used.

PMID- 12812446
TI  - Experimental evaluation of validity of simplified Monte Carlo method in proton
      dose calculations.
AB  - It is important for proton therapy to calculate dose distributions accurately in
      treatment planning. Dose calculations in the body for treatment planning are
      converted to dose distributions in water, and the converted calculations are then
      generally evaluated by the dose measurements in water. In this paper, proton dose
      calculations were realized for a phantom simulating a clinical heterogeneity.
      Both dose calculations in the phantom calculated by two dose calculation methods,
      the range-modulated pencil beam algorithm (RMPBA) and the simplified Monte Carlo
      (SMC) method, and dose calculations converted to dose distributions in water by
      the same two methods were verified experimentally through comparison with
      measured distributions, respectively. For the RMPBA, though the converted
      calculations in water agreed moderately well with the measured ones, the
      calculated results in the actual phantom produced large errors. This meant that
      dose calculations in treatment planning should be evaluated by the dose
      measurements not in water but in the body with heterogeneity. On the other hand,
      the results calculated in the phantom, even by the less rigorous SMC method,
      reproduced the experimental ones well. This finding showed that actual dose
      distributions in the body should be predicted by the SMC method.

PMID- 12812447
TI  - Smoothing Monte Carlo calculated dose distributions by iterative reduction of
      noise.
AB  - A smoothing algorithm based on an optimization procedure is presented and
      evaluated for single electron and photon beams and a full intensity modulated
      radiation therapy (IMRT) delivery. The algorithm iteratively reduces the
      statistical noise of Monte Carlo (MC) calculated dose distributions. It is called
      IRON (iterative reduction of noise). By varying the dose in each voxel, the
      algorithm minimizes the second partial derivatives of dose with respect to X, Y
      and Z. An additional restoration term ensures that too large dose changes are
      prevented. IRON requires a MC calculated one-dimensional or three-dimensional
      dose distribution with or without known statistical uncertainties as input. The
      algorithm is tested using three different treatment plan examples, a photon beam
      dose distribution in water, an IMRT plan of a real patient and an electron beam
      dose distribution in a water phantom with inhomogeneities. It is shown that
      smoothing can lead to an additional reduction of MC calculation time by factors
      of 2 to 10. This is especially useful if MC dose calculation is part of an
      inverse treatment planning system. In addition to this, it is shown that
      smoothing a noisy dose distribution may introduce some bias into the final dose
      values by converting the statistical uncertainty of the dose distribution into a
      systematic deviation of the dose value.

PMID- 12812448
TI  - Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of
      ovarian cancer micrometastases.
AB  - A simple model has been developed to investigate the dosimetry of micrometastases
      in the peritoneal cavity during intraperitoneal targeted liposomal
      radioimmunotherapy. The model is applied to free-floating tumours with radii
      between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources:
      free liposomes in solution in the peritoneal cavity and liposomes bound to the
      surface of the micrometastases. It is assumed that liposomes do not penetrate
      beyond the surface of the tumours and that the total amount of surface antigen
      does not change over the course of treatment. Integrated tumour doses are
      expressed as a function of biological parameters that describe the rates at which
      liposomes bind to and unbind from the tumour surface, the rate at which liposomes
      escape from the peritoneal cavity and the tumour surface antigen density.
      Integrated doses are translated into time-dependent tumour control probabilities
      (TCPs). The results of the work are illustrated in the context of a therapy in
      which liposomes labelled with Re-188 are targeted at ovarian cancer cells that
      express the surface antigen CA-125. The time required to produce a TCP of 95% is
      used to investigate the importance of the various parameters. The relative
      contributions of surface-bound radioactivity and unbound radioactivity are used
      to assess the conditions required for a targeted approach to provide an
      improvement over a non-targeted approach during intraperitoneal radiation
      therapy. Using Re-188 as the radionuclide, the model suggests that, for
      microscopic tumours, the relative importance of the surface-bound radioactivity
      increases with tumour size. This is evidenced by the requirement for larger
      antigen densities on smaller tumours to affect an improvement in the time
      required to produce a TCP of 95%. This is because for the smallest tumours
      considered, the unbound radioactivity is often capable of exerting a tumouricidal
      effect before the targeting agent has time to accumulate significantly on the
      tumour surface.

PMID- 12812449
TI  - Beam delivery sequencing for intensity modulated proton therapy.
AB  - Methods of beam fluence sequencing for intensity modulated proton therapy (IMPT)
      using the beam scanning technique are presented. Proton beam weight maps
      optimized by the treatment planning system (TPS) for a discrete set of regularly
      spaced narrow pencil beams were interpolated, using convolution with various
      kernel functions, to simulate continuous beam scanning on a raster pattern.
      Expected dose distributions at the proton Bragg peak range were then calculated
      and compared to those planned by the TPS, to evaluate the discrepancy due to the
      differences between the treatment planning and delivery approaches. An
      iteratively optimized adjustment was applied to the simulated continuous beam
      fluence profiles to reduce such discrepancy. Calculation showed that by
      accounting for the specifics of the scanning method, the planned dose
      distribution on the target may be reproduced to within 0.5% of the maximum target
      dose, given the pencil beam spacing smaller or equal to the beam sigma is used
      for treatment planning. For the beam weight maps generated using a spot spacing
      larger than sigma, a substantial reduction in the calculated dose discrepancy may
      be attained by applying an iterative adjustment of fluence profiles obtained by
      interpolating over artificially expanded set of beam spots.

PMID- 12812450
TI  - Aperture modulated arc therapy.
AB  - We show that it is possible to translate an intensity modulated radiation therapy
      (IMRT) treatment plan and deliver it as a single arc. This technique is referred
      to in this paper as aperture modulation arc therapy (AMAT). During this arc, the
      MLC leaves do not conform to the projection of the target PTV and the machine
      output of the accelerator has a constant value. Dose was calculated using the
      CORVUS 4.0 IMRT system, which uses a pencil beam dose algorithm, and treatments
      were delivered using a Varian 2100C/D Clinac. Results are presented for a head
      and neck and a prostate case, showing the equivalence of the IMRT and the
      translated AMAT delivery. For a prostate AMAT delivery, coronal plane film dose
      for the IMRT and AMAT deliveries agreed within 7.19 +/- 6.62%. For a meningioma
      the coronal plane dose distributions were similar to a value of 4.6 +/- 6.62%.
      Dose to the isocentre was measured as being within 2% of the planned value in
      both cases.

PMID- 12812451
TI  - Measurement of the tissue to A-150 tissue equivalent plastic kerma ratio at two
      p(66)Be neutron therapy facilities.
AB  - The ICRU tissue to A-150 tissue equivalent plastic kerma ratio is needed for
      neutron therapy dosimetry. The current ICRU protocol for neutron dosimetry
      recommends using a common conversion factor of 0.95 at all high-energy neutron
      therapy facilities. In an effort to determine facility specific ICRU tissue to A
      150 plastic kerma ratios, an experimental approach was pursued. Four low pressure
      proportional counters that differed in wall materials (i.e. A-150, carbon,
      zirconium and zirconium-oxide) were used as dosimeters and integral kerma ratios
      were determined directly in the clinical beam. Measurements were performed at two
      p(66)Be facilities: iThemba LABS near Cape Town and Fermilab near Chicago. At the
      iThemba facility the clinical neutron beam is routinely filtered by a flattening
      and hardening filter combination. The influence of beam filtration on the kerma
      ratio was evaluated. Using two recent gas-to-wall dose conversion factor (r(m,g)
      value) evaluations a mean ICRU tissue to A-150 plastic kerma ratio of 0.93 +/-
      0.05 was determined for the clinical beam at iThemba LABS. The respective value
      for the Fermilab beam is 0.95 +/- 0.05. The experimentally determined ICRU tissue
      to A-150 plastic kerma ratios for the two clinical beams are in agreement with
      theoretical evaluations. Beam filtration reduces the kerma ratio by 3 +/- 2%.

PMID- 12812452
TI  - Effects of anisotropic optical properties on photon migration in structured
      tissues.
AB  - It is often adequate to model photon migration in human tissue in terms of
      isotropic diffusion or random walk models. A nearly universal assumption in
      earlier analyses is that anisotropic tissue optical properties are satisfactorily
      modelled by using a transport-corrected scattering coefficient which then allows
      one to use isotropic diffusion-like models. In the present paper we introduce a
      formalism, based on the continuous-time random walk, which explicitly allows the
      diffusion coefficients to differ along the three axes. The corrections
      necessitated by this form of anisotropy are analysed in the case of continuous
      wave and time-resolved measurements and for both reflectance and transmission
      modes. An alternate model can be developed in terms of a continuous-time random
      walk in which the times between successive jumps differ along the three axes, but
      is not included here.

PMID- 12812453
TI  - Specificity of noninvasive blood glucose sensing using optical coherence
      tomography technique: a pilot study.
AB  - Noninvasive monitoring of blood glucose concentration in diabetic patients would
      significantly reduce complications and mortality associated with this disease. In
      this paper, we experimentally and theoretically studied specificity of
      noninvasive blood glucose monitoring with the optical coherence tomography (OCT)
      technique. OCT images and signals were obtained from skin of Yucatan micropigs
      and New Zealand rabbits. Obtained results demonstrate that: (1) several body
      osmolytes may change the refractive index mismatch between the interstitial fluid
      (ISF) and scattering centres in tissue, however the effect of the glucose is
      approximately one to two orders of magnitude higher; (2) an increase of the ISF
      glucose concentration in the physiological range (3-30 mM) may decrease the
      scattering coefficient by 0.22% mM(-1) due to cell volume change; (3) stability
      of the OCT signal slope is dependent on tissue heterogeneity and motion
      artefacts; and (4) moderate skin temperature fluctuations (+/- 1 degree C) do not
      decrease accuracy and specificity of the OCT-based glucose sensor, however
      substantial skin heating or cooling (several degrees C) significantly change the
      OCT signal slope. These results suggest that the OCT technique may provide blood
      glucose concentration monitoring with sufficient specificity under normal
      physiological conditions.

PMID- 12812454
TI  - Temporal comparison of functional brain imaging with diffuse optical tomography
      and fMRI during rat forepaw stimulation.
AB  - The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total
      haemoglobin ([HbT]) concentration changes following cortical activation in rats
      by electrical forepaw stimulation were measured using diffuse optical tomography
      (DOT) and compared to similar measurements performed previously with fMRI at 2.0
      T and 4.7 T. We also explored the qualitative effects of varying stimulus
      parameters on the temporal evolution of the hemodynamic response. DOT images were
      reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to
      bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16
      detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time
      courses were compared to the fMRI BOLD time course during stimulation, and the
      DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time
      course. We believe that DOT and fMRI can provide similar temporal information for
      both blood volume and deoxyhaemoglobin changes, which helps to cross-validate
      these two techniques and to demonstrate that DOT can be useful as a complementary
      modality to fMRI for investigating the hemodynamic response to neuronal activity.

PMID- 12812455
TI  - Subset-dependent relaxation in block-iterative algorithms for image
      reconstruction in emission tomography.
AB  - This paper presents a row-action maximum likelihood algorithm (RAMLA), in which
      the relaxation parameter is controlled in such a way that the noise propagation
      from projection data to the reconstructed image is substantially independent of
      the access order of the input data (subsets) in each cycle of the sub-iterations.
      The 'subset-dependent' relaxation parameter lambda(k) (q) is expressed as
      lambda(k)(q) = beta0/(beta0 + q + gamma k M), where M is the number of angular
      views, q (0 < or = q < or = M - 1) is the access order of the angular view, k is
      the iteration number and beta0 and gamma are constants. The constant beta0 deals
      with the balance of the noise propagation and the constant gamma controls the
      convergence of iterations. The value of beta0 is determined from the geometrical
      correlation coefficients among lines of coincidence response. The proposed RAMLA
      using the subset-dependent (dynamic) relaxation 'dynamic RAMLA (DRAMA)' provides
      a reasonable signal-to-noise ratio with a satisfactory spatial resolution by a
      few iterations in the two-dimensional image reconstruction for PET. Dynamic OS-EM
      (DOSEM) has also been developed, which allows the use of a larger number of
      subsets (OS level) Msub without loss of signal-to-noise ratio as compared to the
      conventional OS-EM. DRAMA is a special case of DOSEM, where Msub = M, and it is
      no more profitable to use DOSEM with a smaller Msub (< M), because DRAMA provides
      similar performance with the fastest convergence and smallest computer burden.
      This paper describes the theory, algorithm and the results of the simulation
      studies on the performance of DRAMA and DOSEM.

PMID- 12812456
TI  - Coronary calcium scoring: modelling, predicting and correcting for the effect of
      CT scanner spatial resolution on Agatston and volume scores.
AB  - The purpose of this study was to evaluate the impact of spatial resolution on
      coronary calcium scoring by x-ray CT, to assess the scoring performance of
      different CT scanners as they are operated in the field and to correct for the
      effects of CT scanner spatial resolution on coronary calcium scoring. A phantom
      consisting of five aluminium wires of known diameter in water was used to measure
      spatial resolution and to assess scoring performance. Fourteen CT scanners (three
      helical, two dual, two electron-beam and seven multi-detector) from four
      manufacturers were evaluated, some under different operating conditions. One
      scanner was monitored over a 3 month period and again 6 months later. Both
      spatial resolution and image pixel size significantly affect calcium scoring
      results. Spatial resolution can be measured with a precision of about 2%. Scanner
      spatial resolution ranged from 1 to 1.7 mm full-width-half-maximum (FWHM), and
      pixel size from 0.25 to 0.86 mm. Spatial resolution differences introduce
      systematic scoring differences that range from 38% to 1100% depending on wire
      size. Significant temporal variations in spatial resolution were observed in the
      monitored scanner. By correcting all the scanners to the same target spatial
      resolution, the standard deviation of individual scanners with respect to a mean
      value (the spread) can be reduced by 25-70% for different wires. In conclusion,
      scanner spatial resolution significantly affects calcium scoring and should be
      controlled for. Scanner performance can change over time. Under ideal conditions,
      CT scanners should be operated with a standard spatial resolution for calcium
      scoring. When this is not possible, post-processing correction is a viable
      alternative.

PMID- 12812457
TI  - Statistical inversion for medical x-ray tomography with few radiographs: I.
      General theory.
AB  - In x-ray tomography, the structure of a three-dimensional body is reconstructed
      from a collection of projection images of the body. Medical CT imaging does this
      using an extensive set of projections from all around the body. However, in many
      practical imaging situations only a small number of truncated projections are
      available from a limited angle of view. Three-dimensional imaging using such data
      is complicated for two reasons: (i) typically, sparse projection data do not
      contain sufficient information to completely describe the 3D body, and (ii)
      traditional CT reconstruction algorithms, such as filtered backprojection, do not
      work well when applied to few irregularly spaced projections. Concerning (i),
      existing results about the information content of sparse projection data are
      reviewed and discussed. Concerning (ii), it is shown how Bayesian inversion
      methods can be used to incorporate a priori information into the reconstruction
      method, leading to improved image quality over traditional methods. Based on the
      discussion, a low-dose three-dimensional x-ray imaging modality is described.

PMID- 12812458
TI  - Statistical inversion for medical x-ray tomography with few radiographs: II.
      Application to dental radiology.
AB  - Diagnostic and operational tasks in dental radiology often require three
      dimensional information that is difficult or impossible to see in a projection
      image. A CT-scan provides the dentist with comprehensive three-dimensional data.
      However, often CT-scan is impractical and, instead, only a few projection
      radiographs with sparsely distributed projection directions are available.
      Statistical (Bayesian) inversion is well-suited approach for reconstruction from
      such incomplete data. In statistical inversion, a priori information is used to
      compensate for the incomplete information of the data. The inverse problem is
      recast in the form of statistical inference from the posterior probability
      distribution that is based on statistical models of the projection data and the a
      priori information of the tissue. In this paper, a statistical model for three
      dimensional imaging of dentomaxillofacial structures is proposed. Optimization
      and MCMC algorithms are implemented for the computation of posterior statistics.
      Results are given with in vitro projection data that were taken with a commercial
      intraoral x-ray sensor. Examples include limited-angle tomography and full-angle
      tomography with sparse projection data. Reconstructions with traditional
      tomographic reconstruction methods are given as reference for the assessment of
      the estimates that are based on the statistical model.

PMID- 12812460
TI  - Routine laser assisted hatching results in significantly increased clincal
      pregnancies.
AB  - PURPOSE: To elucidate the appropriateness of current indications for assisted
      hatching (AH) in cleavage stage human embryos and to confirm our preliminary
      findings that only young patients (about 67%) benefit from AH. METHODS: Prior to
      transfer, 2 of 3 embryos selected for ET were subjected to laser assisted
      hatching (LAH). Control group consisted of patients matched by similar
      characteristics and protocol except LAH was not performed. RESULTS: The clinical
      pregnancy rate in women < or = 36 years was 64.9% (24/37) for embryos subjected
      to LAH but was significantly lower (p = 0.029) in the control (33.3%; 10/30). The
      implantation rate in women < or = 36 years in the test group was 38.1% (40/105)
      that was significantly higher than that of the control group (17.5%, 14/80; p =
      0.0039). CONCLUSIONS: LAH is beneficial for women < or = 36 years but not for
      women > or = 37 years, for embryos with thin zonae (< or = 16 micron) but not
      with thick zonae (> or = 17 micron), and for those with repeated failures (37
      50%).

PMID- 12812459
TI  - Inhibin B predicts oocyte number and the ratio IGF-I/IGFBP-1 may indicate oocyte
      quality during ovarian hyperstimulation for in vitro fertilization.
AB  - PURPOSE: To perform a retrospective analysis of 62 age-matched IVF-treated women
      in order to investigate whether levels of inhibin B, IGF-I, and IGFBP-1 in serum
      2 days before oocyte retrieval and in follicular fluid at the day of oocyte
      retrieval might be useful as indicators of the ovarian ability to produce oocytes
      (ovarian reserve). METHODS: Patients were allocated into three groups on the
      basis of the number of oocytes retrieved. Group 1 ("low responders") had 0-3
      oocytes, group 2 ("normal responders") had 6-11 oocytes, and group 3 ("high
      responders") had 12 oocytes or more. Levels of inhibin B, IGF-I, and IGFBP-1 in
      follicular fluid and in serum obtained 2 days before oocyte retrieval were
      analyzed and correlated to clinical parameters including estradiol levels,
      progesterone levels, follicle size, follicle number, and oocyte number. RESULTS:
      We found significant differences in inhibin B levels in the three groups. Inhibin
      B levels in follicular fluid and serum was strongly correlated to the number of
      oocytes retrieved (p < 0.01). The number of oocytes retrieved were also
      correlated to total FSH dose (p < 0.05), to estradiol 2 days before and at ovum
      pick-up (p < 0.05), to progesterone at ovum pick-up (p < 0.0001), to progesterone
      at embryo transfer (p < 0.05), and to the number of follicles (size 12-15 mm, p <
      0.001, size > 15 mm, p < 0.01). Serum inhibin B also correlated to follicular
      fluid inhibin B (p < 0.01). Inhibin B was not correlated to pregnancy. In
      contrast, the ratio IGF-I/IGFBP-1 in serum as well as in follicular fluid was
      significantly higher in women who became pregnant (p < 0.05). CONCLUSIONS: The
      results show that inhibin B in serum 2 days before oocyte retrieval predicts
      number of oocytes retrieved. Since inhibin B in serum before oocyte retrieval in
      ovarian hyperstimulation was strongly predictive of the number of oocytes
      retrieved, it appears useful as a marker for ovarian response. Inhibin B did not
      predict treatment outcome, whereas the ratio IGF-I/IGFBP-1 in serum and
      follicular fluid was significantly higher in women who became pregnant. The ratio
      IGF-I/IGFBP-1 may thus reflect oocyte quality.

PMID- 12812461
TI  - Oocyte and embryo quality in patients with excessive ovarian response during in
      vitro fertilization treatment.
AB  - PURPOSE: This study examined oocyte and embryo quality in patients having
      excessive ovarian responses during assisted reproduction treatment. METHODS: Two
      hundred and seventy-eight women of age <40 years using a long protocol of
      pituitary downregulation in their first intracytoplasmic sperm injection cycle
      indicated for severe male factors were retrospectively evaluated. Those with
      serum estradiol concentration on the day of HCG <10,000, 10,000-20,000, and
      >20,000 pmol/L were classified into Group A, Group B, and Group C, respectively.
      RESULTS: The percentage of metaphase II oocytes (85%), fertilization rate (60
      66%), and distribution of blastomere number per embryo were similar among the
      three groups. The proportion of transferable embryos was not reduced in Group C
      when compared to those of Groups A and B. CONCLUSION: Excessive ovarian response
      does not compromise oocyte and embryo quality in humans. Freezing of all embryos
      is recommended in these patients in view of associated impaired endometrial
      receptivity.

PMID- 12812462
TI  - Fertilization potential of human sperm is correlated with endogenous platelet
      activating factor content.
AB  - PURPOSE: Platelet-activating factor (PAF) is a potent signaling phospholipid that
      is found in mammalian sperm and has a positive correlation with fertility.
      Whereas PAF is present in human sperm, there are no relational reports on its
      content and the cells fertilization potential. Therefore, the study objective was
      to determine if PAF content in capacitated-induced sperm is related to
      fertilization potential as determined by the sperm penetration assay (SPA).
      METHODS: Endogenous sperm lipids were measured for PAF content by a specific
      radioimmunoassay following insemination of zona pellucida-free hamster ova. Data
      were analyzed by regression analysis and Student's t test. RESULTS: Regression
      analysis revealed a positive and significant relation (R2 = 0.806; P < 0.05)
      between PAF content in human sperm and SPA outcome (pass: > or = 5.0; fail: <
      5.0, penetrations/ova). Patients that passed (22.61 +/- 5.21 picomoles/10(6)) the
      SPA had significantly (P < 0.01) higher PAF levels in their sperm than patients
      that failed (12.91 +/- 1.76 picomoles/10(6) cells) the test. CONCLUSIONS: PAF
      content in capacitated-induced sperm has a significant and positive relationship
      with fertilization potential. Fertilization potential may be predicted by
      measuring PAF levels in capacitation-induced human sperm. Determining PAF content
      in capacitated human sperm may be a beneficial diagnostic tool for the
      infertility specialist.

PMID- 12812463
TI  - High sex chromosome aneuploidy and diploidy rate of epididymal spermatozoa in
      obstructive azoospermic men.
AB  - PURPOSE: To evaluate the frequencies of sex chromosome aneuploidy and diploidy
      rate of epididymal spermatozoa from obstructive azoospermic men and its impact on
      intracytoplasmic sperm injection (ICSI) outcomes. METHODS: Epididymal spermatozoa
      retrieved from 24 obstructive azoospermic men and ejaculated spermatozoa from 24
      fertile donors were analyzed using triple color fluorescence in situ
      hybridization (FISH) techniques, in order to investigate the rates of diploidy
      and aneuploidy for chromosomes 18, X and Y. RESULTS: Epididymal spermatozoa from
      obstructive azoospermic men had total sex aneuploidy, disomy 18, and diploidy
      rates significantly higher than ejaculated spermatozoa from normozoospermic
      fertile controls (1.44% vs 0.14%, 0.11% vs 0.02%, and 0.18% vs 0.02%,
      respectively; p < 0.005). There were no statistically significant differences in
      ICSI outcomes between the patients who had high and low epididymal sperm
      aneuploidy rate. CONCLUSIONS: Epididymal spermatozoa from obstructive azoospermic
      patients had an elevated sex chromosome aneuploidy and diploidy rate. The
      increased frequency of chromosomal abnormalities did not have a direct effect on
      the ICSI outcome.

PMID- 12812464
TI  - Hypothesis: controlled necrosis as a tool for immunotherapy of human cancer.

PMID- 12812465
TI  - A Rh(I)-catalyzed cycloisomerization of homo- and bis-homopropargylic alcohols.
AB  - The ability to form rhodium-vinylidene complexes in situ from terminal alkynes
      has led to the development of a catalytic process, the cycloisomerization of
      homopropargylic and bis-homopropargylic alcohols to dihydrofurans and
      dihydropyrans. Among the transition metals that perform similar reactions,
      rhodium catalysts demonstrate the best chemoselectivity and turnover numbers to
      date. Both secondary and tertiary alcohols participate equally well. The presence
      of proparylic oxygen and nitrogen functionality, which potentially can be induced
      to ionize via formation of allenylidene metal complexes, is compatible with this
      catalyst. The formation of a 5-amino-dihydropyran which is not compatible with
      some of the previous catalysts proceeds in good yield with the rhodium catalysts.
      A substrate bearing a benzylic hydroxyl group adjacent to an electron-rich
      aromatic ring also participates without complications of ionization. The method
      provides access to useful aminosugars. A mechanism to account for the different
      selectivity of this catalyst as compared to others is proposed.

PMID- 12812466
TI  - The first total synthesis of nakadomarin A.
AB  - (-)-Nakadomarin A is a member of manzamine alkaloid isolated from a marine sponge
      and have a unique hexacyclic structure. The first total synthesis of (+)
      nakadomarin A, an enantiomer of natural product, has been accomplished from
      stereochemically defined 4-oxopiperidin-3-carboxylic acid derivative. The
      synthesis established the structure of nakadomarin A including absolute
      configuration.

PMID- 12812467
TI  - Sigmasigma* transition in anti,cisoid alternating oligosilanes: clear-cut
      evidence for suppression of conjugation effect by a cisoid turn.
AB  - On the basis of the UV absorption spectra of the anti,cisoid alternating
      oligosilanes, the first experimental clear-cut evidence was presented for the
      generally accepted idea that the sigma conjugation in polysilanes does not
      effectively extend through a tetrasilane fragment with a small dihedral angle
      such as a cisoid turn.

PMID- 12812468
TI  - Dynamics of a surface phase transition as monitored by in situ second harmonic
      generation.
AB  - The dynamics of the (2 x 2)-3CO <--> dilute phase transition involving CO
      adsorbed on Pt(111) microfacets has been monitored in situ in a CO-saturated
      acidic electrolyte using potential step-second harmonic generation techniques.
      Apparent time constants derived strictly from the optical data were found to be
      orders of magnitude slower for the forward process as compared to those of the
      reverse process. This behavior is consistent with the activated nature of CO
      electrooxidation, which requires the presence of a neighboring adsorbed
      oxygenated species, for example, hydroxyl, for the process to ensue.

PMID- 12812469
TI  - Is it possible to estimate the enantioselectivity of a chiral catalyst from its
      racemic mixture?
AB  - The evaluation of a racemic catalyst was investigated in the case of
      oxazaborolidine (OAB)-catalyzed borane reduction of 1,5-diphenyl-1,5
      pentanedione, giving the corresponding diol. On the basis of the
      diastereoselectivity of the diols, it is possible to estimate the
      enantioselectivity (ee) of the first step, which correlates well with the ee in
      the reaction of the structurally similar phenyl n-pentyl ketone with enantiopure
      OAB catalyst. The measure of diastereoselectivity could be a tool for screening
      racemic catalysts without the need for resolving the individual enantiomers, if
      in the second step of the process there is no substrate control and no catalyst
      scrambling.

PMID- 12812471
TI  - Nanocoatings onto arteries via layer-by-layer deposition: toward the in vivo
      repair of damaged blood vessels.
AB  - The deposition of polysaccharide-based self-assembled nanocoatings onto damaged
      arteries is described as a means not only to protect a damaged artery against
      thrombogenesis, but also to control the healing processes by incorporating
      biologically active components within the multilayer. As shown by confocal
      microscopy, the polysaccharide multilayer was retained on the artery in
      physiological condition and prevented platelet adhesion. Diffusion of the
      polysaccharides within the artery was also observed and may be used to
      efficiently target the vascular wall. The NO-precursor l-arginine was used a drug
      model and incorporated within the self-assembled layers.

PMID- 12812470
TI  - Bovine serum albumin-mediated enantiodifferentiating photocyclodimerization of 2
      anthracenecarboxylate.
AB  - Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxyalate (AC)
      was performed at 25 degrees C in aqueous buffer solution (pH 7) in the presence
      of bovine-serum albumin (BSA) to afford four [4 + 4] cyclodimers, i.e., anti- and
      syn-head-to-tail (HT) (1 and 2) and anti- and syn-head-to-head (HH) dimers (3 and
      4), of which only 2 and 3 are chiral. We found that (1) BSA possesses four sets
      of binding sites for AC of different affinities, stoichiometries, and chiral
      environment for photoreaction, which bind 1, 3, 2, and 3 AC molecules with
      binding constants of 5.3 x 107, 1.3 x 105, 1.4 x 104, and 3.0 x 103 M-1,
      respectively, (2) the regioselectivity of photodimerization is switched from HT
      to HH by adding BSA (the HH/HT ratio varies from 0.28 to 4.3), (3) BSA-mediated
      photodimerization of AC affords optically active products 2 and 3 of up to 29%
      and 41% ee, respectively. It is emphasized that the selective excitation of bound
      substrate, utilizing the spectral shift upon complexation with BSA, is not a
      prerequisite for efficient photochirogenesis using biomolecules.

PMID- 12812472
TI  - Direct observation of the protonation state of an imino sugar glycosidase
      inhibitor upon binding.
AB  - Glycosidases are some of the most ubiquitous enzyme in nature. Their biological
      significance, coupled to their enormous catalytic prowess derived from tight
      binding of the transition state, is reflected in their importance as therapeutic
      targets. Many glycosidase inhibitors are known. Imino sugars are often potent
      inhibitors, yet many facets of their mode of action, such as their degree, if
      any, of transition-state "mimicry" and their protonation state when bound to the
      target glycosidase remain unclear. Atomic resolution analysis of the
      endoglucanase, Cel5A, in complex with a cellobio-derived isofagomine in
      conjunction with the pH dependence of Ki and kcat/KM reveals that this compound
      binds as a protonated sugar. Surprisingly, both the enzymatic nucleophile and the
      acid/base are unprotonated in the complex.

PMID- 12812473
TI  - Modification of silicon AFM cantilever tips with an oligo(ethylene glycol)
      derivative for resisting proteins and maintaining a small tip size for high
      resolution imaging.
AB  - We demonstrate that silicon AFM tips can be modified by etching with 2% HF
      solution followed by reaction with an alpha,omega-oligo(ethylene glycol)alkene.
      Tips properly modified by this technique maintain a small tip size and
      effectively reduce the nonspecific interaction with fibrinogen and bovine serum
      albumin, resulting in greatly improved image resolution and contrast for high
      coverage fibrinogen films.

PMID- 12812474
TI  - Protein prosthesis: a nonnatural residue accelerates folding and increases
      stability.
AB  - Nonnatural residues can endow proteins with desirable properties. Here, replacing
      a proline residue that has a cis peptide bond in native ribonuclease A with 5,5
      dimethyl-l-proline is shown to accelerate protein folding by 6-fold and enhance
      conformational stability by DeltaTm = 2.8 +/- 0.3 degrees C while having no
      effect on enzymatic activity. The rational use of this and other prosthetic
      segments could enable chemotherapeutic proteins to survive longer in vivo or
      retain activity after oral administration.

PMID- 12812475
TI  - Cobalt-substituted zinc finger 3 of transcription factor IIIA: interactions with
      cognate DNA detected by (31)P ENDOR spectroscopy.
AB  - We show the first ENDOR study of the coordination environment of high-spin Co(II)
      in a biological system with a study of DNA binding to the Co-substituted
      Cys2/His2 single Zn-finger domain, Finger 3 (F3), from the prototypical zinc
      finger protein, transcription factor IIIA (TFIIIA) from Xenopus laevis. High
      covalency to cysteine and histidine is implied by ENDOR-derived 1H couplings to
      protons of cysteinyl ligands and 14N couplings to histidyl nitrogens, results
      which support the expectation that Zn(II) and Co(II) bind to F3 in a very similar
      manner. No changes in either 1H or 14N ENDOR were detected upon binding Co(II)-F3
      to C-block DNA. Of particular importance to the use of Co(II) substitution for
      Zn(II), the ENDOR method shows that Co(II)-F3 undergoes sequence-specific binding
      to the cognate DNA for Zn(II)-F3, the internal control region (ICR) of the 5S
      rRNA (C-block). 31P ENDOR measurements yield a Co-31P distance of rCo-P = 8.1(3)
      A to the nearest backbone phosphodiester of the C-block. Interestingly, a 31P
      ENDOR doublet observed for Co(II)-F3 in phosphate buffer indicates that inorganic
      phosphate (Pi) binds at a comparable distance from Co as does the nearest
      phosphate of DNA, presumably at the same site.

PMID- 12812476
TI  - When does gold behave as a halogen? Predicted uranium tetraauride and other MAu4
      tetrahedral species, (M = Ti, Zr, Hf, Th).
AB  - Quantum chemical calculations suggest that a series of molecules with the general
      formula MAu4 are stable, where M = U, Th, and a group-4 atom. They correspond to
      Au in the formal valence state -1 and indicate that gold can act as a ligand
      similar to the halogen series. Of the MAu4 species studied, UAu4, the first
      predicted mixed gold uranium compound, has a short M-Au bond distance, 2.71 A,
      which would locate Au between Br and I from the bond length point of view in the
      U-tetrahalide series. Energetically, the U-Au bond is weaker than the
      corresponding U-Br and U-I bonds.

PMID- 12812477
TI  - Addition of arenes to ethylene and propene catalyzed by ruthenium.
AB  - TpRuII(CO)(Me)(NCMe) (Tp = hydridotris(pyrazolyl)borate) serves as a catalyst
      precursor for the conversion of benzene and ethylene or propene to alkylaromatic
      products. The reaction proceeds via the formation of the active catalyst
      TpRu(CO)(Ph)(NCMe) and is mildly selective for linear propylbenzene over
      isopropylbenzene.

PMID- 12812478
TI  - Enantioselective Michael reaction catalyzed by well-defined chiral ru amido
      complexes: isolation and characterization of the catalyst intermediate, ru
      malonato complex having a metal-carbon bond.
AB  - Chiral Ru amido complexes promote asymmetric Michael addition of malonates to
      cyclic enones, leading to Michael adducts with excellent ee's, in which the
      chiral Ru amido complexes react with malonates to give isolable catalyst
      intermediates, chiral Ru malonato complexes bearing a metal bound C-nucleophile.

PMID- 12812479
TI  - Determining dihedral angles and local structure in silk peptide by 13C-2H REDOR.
AB  - 13C-2H REDOR NMR experiments were performed on 30-residue (AlaGly)15 silk I
      mimics of Bombyx mori silk fibroin to gain structural details about the elusive
      structure of the silk I conformation. 13C,2H-labeling strategies are illustrated
      for measuring individual dihedral angles in peptides and for determining local
      structure by REDOR. A major turn of type II character is found in the region
      Gly(14)-Ala(17).

PMID- 12812480
TI  - Breaking the degeneracy of the genetic code.
AB  - A mutant yeast phenylalanine transfer RNA (ytRNAPheAAA) containing a modified
      (AAA) anticodon was generated to explore the feasibility of breaking the
      degeneracy of the genetic code in Escherichia coli. By using an E. coli strain co
      transformed with ytRNAPheAAA and a mutant yeast phenylalanyl-tRNA synthetase, we
      demonstrate efficient replacement of phenylalanine (Phe) by L-3-(2
      naphthyl)alanine (Nal) at UUU, but not at UUC codons.

PMID- 12812481
TI  - Formation of highly ordered organic monolayers by dative bonding: pyridine on
      ge(100).
AB  - The adsorption of pyridine onto the Ge(100) surface has been studied using both
      real-time scanning tunneling microscopy (STM) and ab initio pseudopotential
      density functional calculations. The results show that pyridine molecules adsorb
      on the electron-deficient down-Ge atoms of the Ge=Ge dimers via Ge-N dative
      bonding, with the pyridine ring tilted to the surface. The electron-rich up-Ge
      atoms remaining after adsorption of pyridine induce an asymmetric dimer row,
      which is mainly reconstructed to the c(4 x 2) structure. At pyridine coverage of
      0.25 ML, the adsorbed pyridine molecules form a perfectly ordered monolayer. The
      entire Ge substrate underlying this organic monolayer rearranges into the c(4 x
      2) structure.

PMID- 12812482
TI  - Discovery of a potent, non-peptide bradykinin B1 receptor antagonist.
AB  - Bradykinin (BK) plays an important role in the pathophysiological processes
      accompanying pain and inflammation. Selective bradykinin B1 receptor antagonists
      have been shown to be anti-nociceptive in animal models and could be novel
      therapeutic agents for the treatment of pain and inflammation. We have explored
      chemical modifications in a series of dihydroquinoxalinone sulfonamides to
      evaluate the effects of various structural changes on biological activity. The
      optimization of a screening lead compound, facilitated by a homology model of the
      BK B1 receptor, culminated in the discovery of a potent human BK B1 receptor
      antagonist. Results from site-directed mutagenesis studies and experiments in an
      animal pain model are presented.

PMID- 12812483
TI  - Design and characterization of a homodimeric antiparallel coiled coil.
AB  - We report the first successful design of a self-associating antiparallel coiled
      coil, APH. The simultaneous application of Coulombic and hydrophobic components
      results in a decided preference for the antiparallel alignment as judged by HPLC,
      sedimentation equilibrium, and chemical denaturation data. The designed peptide
      is of comparable stability to naturally occurring leucine zipper peptides and can
      be expressed in bacteria. These properties of APH suggest potential in vivo
      protein fusion and biomaterials applications.

PMID- 12812484
TI  - A reversible valence equilibrium in a heavier main group compound.
AB  - The addition of LiPh to Ar*SnCl (Ar* = C6H3-2,6-Trip2; Trip = C6H2-2,4,6-iPr3) at
      low temperature afforded the Sn(1)-Sn(III) species Ar*SnSnPh2Ar*, which exists in
      equilibrium with the Sn(II) compound Ar*SnPh. It is the first example of a room
      temperature equilibrium of compounds involving main group elements in different
      oxidation states.

PMID- 12812485
TI  - Building blocks for the molecular expression of quantum cellular automata.
      Isolation and characterization of a covalently bonded square array of two
      ferrocenium and two ferrocene complexes.
AB  - The suitability of [{(eta5-C5H5)Fe(eta5-C5H4)}4(eta4-C4)Co(eta5-C5H5)][PF6]2,
      [1][PF6]2, for use as a molecular quantum cellular automata (QCA) cell is
      demonstrated. To this end the structure of 1 in the solid state and the
      conversion of 1 to mono- and dicationic mixed-valence complexes have been
      accomplished. The latter compounds have been isolated as pure materials and
      characterized by IR, EPR, and Mossbauer spectroscopies and single-crystal XRD
      (monocation only) and magnetic susceptibility measurements. Near-IR spectra
      demonstrate the mixed valence character of the cations (valence trapped on the
      IR, EPR and Mossbauer time scales), and the energies of the intervalence charge
      transfer bands provide a measure of the hole hopping frequency.

PMID- 12812486
TI  - XANES determination of the platinum oxidation state distribution in cancer cells
      treated with platinum(IV) anticancer agents.
AB  - Here we describe the use of X-ray absorption near edge spectroscopy (XANES) to
      provide information about the relative proportions of platinum(II) and
      platinum(IV) complexes by analyzing the XANES edge height. The intracellular
      reduction of platinum(IV) complexes in cancer cells has been observed directly,
      and the proportion of reduction after 2 h was found to correlate with the
      reduction potentials of the complexes.

PMID- 12812487
TI  - Operational control of stereoselectivity during the enzymatic hydrolysis of
      racemic organophosphorus compounds.
AB  - The wild-type bacterial phosphotriesterase catalyzes the stereoselective
      hydrolysis of racemic pairs of organophosphorus compounds. The enzymatic
      stereoselectivity can be substantially enhanced via systematic alteration of the
      pKa for the leaving group phenol in the target substrates. These changes alter
      the rate-limiting step for substrate turnover from a diffusional event to
      phosphorus-oxygen bond cleavage. Turnover ratios in excess of 5000:1 were
      achieved using phenols with pKa values greater than 8.5. This method has enabled
      the isolation of the RP-enantiomer of 4-acetylphenyl methyl phenylphosphonate
      with an enantiomeric excess of >99% via a kinetic resolution of the racemate.

PMID- 12812488
TI  - High-yield solvothermal formation of magnetic CoPt alloy nanowires.
AB  - One-dimensional (1D) magnetic nanomaterials have attracted much attention
      recently because of their applications in magnetic recording and spintronics.
      Nevertheless, it remains a challenge to prepare free-standing magnetic nanowires
      in high yield. This Communication reports the successful high-yield synthesis of
      an interesting 1D ferromagnetic CoPt alloy by direct decomposition of platinum
      acetylacetonate and cobalt carbonyl compound in ethylenediamine solvent through a
      solvothermal reaction. The CoPt alloy nanowires obtained have a tunable diameter
      of 10-50 nm and a length along the longitudinal axis of up to several microns,
      depending on crystallization temperature and reaction time. A unique formation
      mechanism involving coarsening and ripening under solvothermal conditions was
      discovered. This research opens new opportunities in synthesizing nanomaterials
      through low-temperature solvothermal processes.

PMID- 12812489
TI  - Photolytic control of peptide self-assembly.
AB  - Herein, we present a methodology that allows for the temporal control of
      fibrillization of amyloidogenic peptides. This general approach implements a
      photolabile linker that connects the amyloidogenic peptide to a fibril-inhibitory
      unit, in this case, a pentamer of amino acids modified with the solubilizing N,N
      dimethylethylenediamine (DMDA) units. Upon photolysis, the linker can be
      dissociated to afford the intact and native amyloidogenic peptide. This
      methodology should be of value in a variety of studies where spatial and temporal
      control of supramolecular association processes is desired.

PMID- 12812490
TI  - Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme
      intermediate: tyrosine is the catalytic nucleophile.
AB  - Modified sialic acid substrates have been used to label Trypanosoma cruzi trans
      sialidase, demonstrating that the enzyme catalyses the transfer of sialic acid
      through a covalent glycosyl-enzyme intermediate, a mechanism common to most
      retaining glycosidases. Peptic digestion of labeled protein, followed by LC-MS/MS
      analysis of the digest, identified Tyr342 as the catalytic nucleophile. This is
      the first such example of a retaining glycosidase utilizing an aryl glycoside
      intermediate. It is suggested that this alternative choice of nucleophile is a
      consequence of the chemical nature of sialic acid. A Tyr/Glu couple is invoked to
      relay charge from a remote glutamic acid, thereby avoiding electrostatic
      repulsion with the sialic acid carboxylate group.

PMID- 12812491
TI  - Alkyl complexes of strontium and barium: synthesis and structural
      characterization of [(Me3Si)2(MeOMe2Si)C]2Sr(THF) and
      [(Me3Si)2(MeOMe2Si)C]2Ba(MeOCH2CH2OMe).
AB  - Metathesis between either SrI2 or BaI2 and 2 equiv of {(Me3Si)2(MeOMe2Si)C}K in
      THF yields the novel heavier alkali metal dialkyls {(Me3Si)2(MeOMe2Si)C}2M(L)
      [M(L) = Sr(THF) (2), Ba(DME) (3) (DME = 1,2-dimethoxyethane)] after
      recrystallization.

PMID- 12812492
TI  - Redox-active tyrosine residues: role for the peptide bond in electron transfer.
AB  - Photosystem II (PSII) catalyzes the light-driven oxidation of water and reduction
      of plastoquinone. In PSII, redox-active tyrosine Z conducts electrons between the
      primary chlorophyll donor and the manganese cluster, which is the catalytic site.
      In this report, difference FT-IR spectroscopy is used to show that oxidation of
      redox-active tyrosine Z causes perturbations of the peptide bond. PSII data were
      acquired on control samples, as well as samples in which tyrosine was 2H4 (ring)
      labeled. Comparison to model compound data, acquired both from tyrosinate and its
      2H4 isotopomer, was performed. The PSII FT-IR spectrum exhibited vibrational
      bands that are assignable to imide and amide vibrational modes. In previous work,
      we have shown that oxidation of tyrosinate perturbs the terminal amino group of
      tyrosinate (Ayala, I.; Range, K.; York, D.; Barry, B. A. J. Am. Chem. Soc. 2002,
      124, 5496-5505). Density functional calculations on tyrosinate supported the
      interpretation that the perturbation is due to spin delocalization onto the amino
      group. In tyrosine-containing dipeptides, perturbations of the peptide bond were
      observed. Therefore, the imide and amide perturbations observed here are
      attributed to spin delocalization into the peptide bond in PSII. Migration of the
      electron hole in PSII may be consistent with peptide bond involvement in tyrosyl
      radical-based electron-transfer reactions.

PMID- 12812493
TI  - Assemblage of signaling DNA enzymes with intriguing metal-ion specificities and
      pH dependences.
AB  - We report a group of new DNA enzymes that possess a synchronized RNA
      cleavage/fluorescence-signaling ability and exhibit wide-ranging metal-ion and pH
      dependences. These DNA catalysts were derived from a random-sequence DNA pool in
      a two-stage process: (1) establishment of a catalytic DNA population through
      repetitive rounds of in vitro selection at pH 4.0, and (2) sequence
      diversification and catalytic-activity optimization through five parallel paths
      of in vitro evolution conducted at pH 3.0, 4.0, 5.0, 6.0, and 7.0, respectively.
      The deoxyribozymes were evolved to cleave the phosphodiester bond of a single
      ribonucleotide embedded in DNA and flanked immediately by two
      deoxyribonucleotides modified with a fluorophore and a quencher, respectively--a
      setting that synchronizes catalysis with fluorescence signaling. The most
      dominant catalyst from each pool was examined for metal-ion specificity,
      catalytic efficiency, pH dependence, and fluorescence-signaling capability.
      Individual catalysts have different metal-ion requirements and can generate as
      much as a 12-fold fluorescence enhancement upon RNA cleavage. Most of the DNA
      enzymes have a pH optimum coinciding with the selection pH and exhibit a rate
      constant approximating 1 min(-)(1) under optimal reaction conditions. The
      demonstration of DNA enzymes that are functional under extremely high acidity
      (such as pH 3 and 4) indicates that DNA has the ability to perform efficient
      catalysis even under harsh reaction conditions. The isolation of many new
      signaling DNA enzymes with broad pH optima and metal-ion specificities should
      facilitate the development of diverse deoxyribozyme-based biosensors.

PMID- 12812494
TI  - Comparisons of phosphorothioate with phosphate transfer reactions for a
      monoester, diester, and triester: isotope effect studies.
AB  - Phosphorothioate esters are sometimes used as surrogates for phosphate ester
      substrates in studies of enzymatic phosphoryl transfer reactions. To gain better
      understanding of the comparative inherent chemistry of the two types of esters,
      we have measured equilibrium and kinetic isotope effects for several
      phosphorothioate esters of p-nitrophenol (pNPPT) and compared the results with
      data from phosphate esters. The primary (18)O isotope effect at the phenolic
      group ((18)k(bridge)), the secondary nitrogen-15 isotope effect ((15)k) in the
      nitro group, and (for the monoester and diester) the secondary oxygen-18 isotope
      effect ((18)k(nonbridge)) in the phosphoryl oxygens were measured. The
      equilibrium isotope effect (EIE) (18)k(nonbridge) for the deprotonation of the
      monoanion of pNPPT is 1.015 +/- 0.002, very similar to values previously reported
      for phosphate monoesters. The EIEs for complexation of Zn(2+) and Cd(2+) with the
      dianion pNPPT(2-) were both unity. The mechanism of the aqueous hydrolysis of the
      monoanion and dianion of pNPPT, the diester ethyl pNPPT, and the triester
      dimethyl pNPPT was probed using heavy atom kinetic isotope effects. The results
      were compared with the data reported for analogous phosphate monoester, diester,
      and triester reactions. The results suggest that leaving group bond fission in
      the transition state of reactions of the monoester pNPPT is more advanced than
      for its phosphate counterpart pNPP, while alkaline hydrolysis of the
      phosphorothioate diester and triester exhibits somewhat less advanced bond
      fission than that of their phosphate ester counterparts.

PMID- 12812495
TI  - Computational study of ketosteroid isomerase: insights from molecular dynamics
      simulation of enzyme bound substrate and intermediate.
AB  - Delta(5)-3-Ketosteroid Isomerase (KSI) catalyzes the isomerization of 5,6
      unsaturated ketosteroids to their 4,5-unsaturated isomers at a rate approaching
      the diffusion limit. The isomerization reaction follows a two-step general acid
      base mechanism starting with Asp38-CO(2)(-) mediated proton abstraction from a
      sp(3)-hybridized carbon atom, alpha to carbonyl group, providing a dienolate
      intermediate. In the second step, Asp38-CO(2)H protonates the C6 of the
      intermediate providing a 4,5-unsaturated ketosteroid. The details of the
      mechanism have been highly controversial despite several experimental and
      computational studies of this enzyme. The general acid-base catalysis has been
      proposed to involve either a catalytic diad or a cooperative hydrogen bond
      mechanism. In this paper, we report our results from the 1.5 nanosecond molecular
      dynamics (MD) simulation of enzyme bound natural substrate (E.S) and enzyme bound
      intermediate (E. In) solvated in a TIP3P water box. The final coordinates from
      our MD simulation strongly support the cooperative hydrogen bond mechanism. The
      MD simulation of E.S and E. In shows that both Tyr14 and Asp99 are hydrogen
      bonded to the O3 of the substrate or intermediate. The average hydrogen bonding
      distance between Tyr14-OH and O3 becomes shorter and exhibits less fluctuation on
      E.S --> E. In. We also observe dynamic motions of water moving in and out of the
      active site in the E.S structures. This free movement of water disappears in the
      E. In structures. The active site is shielded by hydrophobic residues, which come
      together and squeeze out the waters from the active site in the E. In complex.

PMID- 12812496
TI  - Optical spectroscopic investigations of model beta-sheet hairpins in aqueous
      solution.
AB  - In this contribution we report optical spectroscopic data on a series of designed
      beta hairpins previously shown by NMR to contain a substantial population of beta
      sheet structure. These models contain a designed hydrophobic cluster and a (D)Pro
      Gly sequence to promote formation of a turn geometry. FTIR, electronic and
      vibrational CD (ECD and VCD) spectra for these small peptides are comparable to
      expected bandshapes for peptides of high beta-sheet content. The (D)Pro-Gly
      sequence provides a better turn motif than Asn-Gly as measured by its beta-sheet
      spectral characteristics. IR and VCD spectra are in qualitative agreement with
      theoretical simulations based on transfer of parameters from ab initio quantum
      mechanical force field and intensity computations for the turn and strands. These
      calculations provide assignments for some distinguishing modes in both IR and VCD
      spectra. Increased sheet structure can be induced in these hairpins by use of
      mixed solvent conditions. Thermal denaturation studies reveal that these hairpins
      undergo very broad unfolding transitions. Guanidine hydrochloride unfolding
      transitions for the selected hairpin models are similarly broad. However, the
      "end-states" of temperature and chaotropic denaturation are spectroscopically
      differentiable.

PMID- 12812498
TI  - A photochromic, electrochromic, thermochromic Ru complexed benzannulene: an
      organometallic example of the dimethyldihydropyrene-metacyclophanediene valence
      isomerization.
AB  - The preparation of the first photochromic, organometallic derivative of the
      diarylethene class, the CpRu-complexed benzodimethyldihydropyrene 3, in which the
      organometallic is directly attached to the photochromic core, is described. The
      negative dark purple photochrome 3 readily bleaches to form the almost colorless
      cyclophanediene 3' on irradiation with visible light. The latter switches back to
      3 either photochromically with UV light, electrochromically on reduction, or
      thermochromically on heating. Essentially quantitative conversion between the two
      states is possible. The open complex 3' thermally closes 2.6 times faster than
      the uncomplexed parent 2', but the closed form 3 opens with visible light at
      about 30% of the rate of uncomplexed 2. Both open forms, complexed 3' and
      uncomplexed 2' close equally fast with UV light.

PMID- 12812497
TI  - A bifunctional molecule that displays context-dependent cellular activity.
AB  - The cell-permeable dihydrofolate reductase inhibitor methotrexate was covalently
      linked to a ligand for the protein FKBP to create a bifunctional molecule called
      MTXSLF. The covalent tether between the two ligands was designed to be
      prohibitively short, so that unfavorable protein-protein interactions between
      DHFR and FKBP preclude formation of a trimeric complex. In vitro and in vivo
      experiments demonstrate that MTXSLF is an effective inhibitor of human DHFR, but
      that efficacy is decreased in the presence of human FKBP due to the high
      concentration of FKBP and its tight affinity for MTXSLF. MTXSLF also inhibits
      Plasmodium falciparum DHFR in vitro, but a low concentration of the weaker
      binding Plasmodium FKBP has no effect on the inhibitory potency of MTXSLF in
      vivo. These studies illustrate a potentially general strategy for modulating the
      biological activity of synthetic molecules that depends on the ligand-binding
      properties of a nontarget protein.

PMID- 12812499
TI  - Comparative kinetic studies of the copolymerization of cyclohexene oxide and
      propylene oxide with carbon dioxide in the presence of chromium salen
      derivatives. In situ FTIR measurements of copolymer vs cyclic carbonate
      production.
AB  - The catalysis of the reaction of carbon dioxide with epoxides (cyclohexene oxide
      or propylene oxide) using the (salen)Cr(III)Cl complex as catalyst, where
      H(2)salen = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexenediimine (1),
      to provide copolymer and cyclic carbonate has been investigated by in situ
      infrared spectroscopy. As previously demonstrated for the cyclohexene oxide/CO(2)
      reaction in the presence of complex 1, coupling of propylene oxide and carbon
      dioxide was found to occur by way of a pathway first-order in catalyst
      concentration. Unlike the cyclohexene oxide/carbon dioxide reaction catalyzed by
      complex 1, which affords completely alternating copolymer and only small
      quantities of trans-cyclic cyclohexyl carbonate, under similar conditions
      propylene oxide/carbon dioxide produces mostly cyclic propylene carbonate.
      Comparative kinetic measurements were performed as a function of reaction
      temperature to assess the activation barrier for production of cyclic carbonates
      and polycarbonates for the two different classes of epoxides, i.e., alicyclic
      (cyclohexene oxide) and aliphatic (propylene oxide). As anticipated in both
      instances the unimolecular pathway for cyclic carbonate formation has a larger
      energy of activation than the bimolecular enchainment pathway. That is, the
      energies of activation determined for cyclic propylene carbonate and
      poly(propylene carbonate) formation were 100.5 and 67.6 kJ.mol(-1), respectively,
      compared to the corresponding values for cyclic cyclohexyl carbonate and
      poly(cyclohexylene carbonate) production of 133 and 46.9 kJ.mol(-1). The small
      energy difference in the two concurrent reactions for the propylene oxide/CO(2)
      process (33 kJ.mol(-1)) accounts for the large quantity of cyclic carbonate
      produced at elevated temperatures in this instance.

PMID- 12812500
TI  - Enantioselective total synthesis of (+)-obtusenyne.
AB  - A total synthesis of the laurencia metabolite (+)-obtusenyne has been completed.
      The key steps include a Sharpless kinetic resolution and an asymmetric glycolate
      alkylation to establish the stereogenic centers adjacent to the ether linkage and
      a ring-closing metathesis reaction to construct the nine-membered ether without
      the aid of a cyclic conformational constraint. The synthesis was completed in 20
      linear steps from commercially available 1,5-hexadiene-3-ol.

PMID- 12812501
TI  - New insights in the mechanism of amine catalyzed epoxidation: dual role of
      protonated ammonium salts as both phase transfer catalysts and activators of
      oxone.
AB  - Amines have previously been reported to catalyze the epoxidation of alkenes using
      Oxone (2KHSO(5)+KHSO(4)+K(2)SO(4)), and significant levels of asymmetric
      induction were observed. From screening a series of amines based on 2-substituted
      pyrrolidines, it has now been found that more consistent and reproducible results
      are achieved with the HCl salt of the amine compared to the amine itself. Up to
      66% ee was achieved in epoxidation of 1-phenylcyclohexene. The chiral amine could
      be reisolated in >90% yield when reactions were conducted at -10 degrees C,
      indicating that the integrity of the amine was maintained during the oxidation
      process. At -10 degrees C, (S)-2-(diphenylmethyl)pyrrolidine 1 reacted with Oxone
      to give a mixture of ammonium salts containing the peroxymonosulfate salt 6b. The
      enantioselectivity obtained with this salt was compared to the amine.HCl salt
      catalyzed process and identical results were observed, indicating that the true
      oxidant was the peroxymonosulfate salt 6b. The relative rates of oxidation of cis
      and trans-beta-methylstyrenes together with the rho value of a series of 1
      arylcyclohexenes were determined. These studies indicated that the amine
      catalyzed process involved electrophilic oxidation. On the basis of these
      findings, a new mechanism is advanced in which the protonated amine not only acts
      as a PTC but also activates Oxone, through hydrogen bonding, toward electrophilic
      attack.

PMID- 12812502
TI  - Billion-fold acceleration of the methanolysis of paraoxon promoted by La(OTf)3 in
      methanol.
AB  - The methanolysis of the insecticide paraoxon (2) was investigated in methanol
      solution containing varying [La(OTf)(3)] (OTf = (-)OS(O)(2)CF(3)) as a function
      of at 25 degrees C. Plots of the pseudo-first-order rate constants (k(obs)) for
      methanolysis as a function of [La(OTf)(3)](total) were obtained under buffered
      conditions from 5.15 to 10.97, and the slopes of the linear parts of these were
      used to determine the second-order rate constants (k(2)(obs)) for the La(3+)
      catalyzed methanolysis of 2. Detailed analysis of the potentiometric titration
      data of La(OTf)(3) in methanol through fits to a multicomponent equilibrium
      mixture of dimers of general stoichiometry La(3+)(2)((-)OCH3)n, where n assumes
      values of 1-5, gives the equilibrium distribution of each as a function of. These
      data, when fit to a second expression describing k(2)(obs) in terms of a linear
      combination of individual rate constants k(2)(2:1), k(2)(2:2).k(2)(2:)n for the
      dimers, allow one to describe the overall catalytic profile in terms of the
      individual contributions. The most catalytically important species are the three
      dimers La(3+)(2)((-)OCH3)1, La(3+)(2)((-)OCH3)2, and La(3+)(2)((-)OCH3)3. The
      catalysis of the methanolysis of 2 is spectacular: a 2 x 10(-3) M solution of
      [La(3+)](total), at neutral, affords a 10(9)-fold acceleration relative to the
      base reaction (t(1/2) approximately 20 s at 8.2) with excellent turnover. A
      mechanism of the catalyzed reaction involving the La(3+)(2)((-)OCH3)2 species is
      proposed.

PMID- 12812504
TI  - Theoretical analysis of the porphyrin-porphyrin exciton interaction in circular
      dichroism spectra of dimeric tetraarylporphyrins.
AB  - Chiral bis-porphyrins are currently the subject of intense interest as chiral
      receptors and as probes in the determination of structure and stereochemistry. To
      provide an improved framework for interpreting the circular dichroism (CD)
      spectra of bis-porphyrins, we have calculated the CD spectra of chiral bis
      porphyrins from three classes: I, where porphyrins can adopt a relatively wide
      range of orientations relative to each other; II, porphyrins have a fixed
      relative orientation; III, porphyrins undergo pi-stacking. The calculations
      primarily utilized the classical polarizability theory of DeVoe, but were
      supplemented by the quantum mechanical matrix method. Class I was represented by
      three isomers of the diester of 5alpha-cholestane-3,17-diol with 5-(4'
      carboxyphenyl)-10,15,20-triphenylporphin (2-alphabeta, 2-betaalpha, 2-betabeta).
      Careful analysis of the torsional degrees of freedom led to two to four minimum
      energy conformers for each isomer, in each of which the phenyl-porphyrin bonds
      had torsional angles near 90 degrees. Libration about these bonds is relatively
      unrestricted over a range of +/-45 degrees. CD spectra in the Soret region were
      calculated as Boltzmann-weighted averages over the low-energy conformers for each
      isomer. Three models were used: the effective transition moment model, in which
      only one of the degenerate Soret components is considered, along the 5-15
      direction; the circular oscillator model, in which both Soret components are
      given equal weight; and the hybrid model, in which the 10-20 oscillator is given
      half the weight of the 5-15 oscillator, to mimic the effect of extensive
      librational averaging about the 5-15 direction. All three models predict Soret
      exciton couplets with signs in agreement with experiment. Quantitatively, the
      best results are given by the hybrid and circular oscillator models. These
      results validate the widely used effective transition moment model for
      qualitative assignments of bis-porphyrin chirality and thus permit application of
      the exciton chirality model. However, for quantitative studies, the circular
      oscillator or hybrid models should be used. The simplified effective transition
      moment and hybrid models are justified by the librational averaging in the class
      I bis-porphyrins and should only be used with such systems. Two class II bis
      porphyrins were also studied by DeVoe method calculations in the circular
      oscillator model, which yielded good agreement with experiment. Class III bis
      porphyrins were represented by 2-alphaalpha, for which the calculations gave
      qualitative agreement. However, limitations in the conformational analysis with
      the close contacts and dynamic effects in these pi-stacked systems preclude
      quantitative results.

PMID- 12812503
TI  - Synthesis-based approach toward direct sandwich immunoassay for ciguatoxin CTX3C.
AB  - Ciguatoxins are the major causative toxins of ciguatera seafood poisoning.
      Limited availability of ciguatoxins has hampered the development of a reliable
      and specific immunoassay for detecting these toxins in contaminated fish.
      Monoclonal antibodies (mAbs) specific against both ends of ciguatoxin CTX3C were
      prepared by immunization of mice with protein conjugates of rationally designed
      synthetic haptens, 3 and 4, in place of the natural toxin. Haptenic groups that
      possess a surface area larger than 400 A(2) were required to produce mAbs that
      can bind strongly to CTX3C itself. A direct sandwich enzyme-linked immunosorbent
      assay (ELISA) using these mAbs was established to detect CTX3C at the ppb level
      with no cross-reactivity against other related marine toxins, including
      brevetoxin A, brevetoxin B, okadaic acid, or maitotoxin.

PMID- 12812505
TI  - Bis(mu-oxo)dicopper in Cu-ZSM-5 and its role in the decomposition of NO: a
      combined in situ XAFS, UV-vis-near-IR, and kinetic study.
AB  - In situ XAFS combined with UV-vis-near-IR spectroscopy are used to identify the
      active site in copper-loaded ZSM-5 responsible for the catalytic decomposition of
      NO. Cu-ZSM-5 was probed with in situ XAFS (i) after O(2) activation and (ii)
      while catalyzing the direct decomposition of NO into N(2) and O(2). A careful R
      space fitting of the Cu K-edge EXAFS data is presented, including the use of
      different k-weightings and the analysis of the individual coordination shells.
      For the O(2)-activated overexchanged Cu-ZSM-5 sample a Cu.Cu contribution at 2.87
      A with a coordination number of 1 is found. The corresponding UV-vis-near-IR
      spectrum is characterized by an intense absorption band at 22 700 cm(-1) and a
      relatively weaker band at 30 000 cm(-1), while no corresponding EPR signal is
      detected. Comparison of these data with the large databank of well-characterized
      copper centers in enzymes and synthetic model complexes leads to the
      identification of the bis(mu-oxo)dicopper core, i.e. [Cu(2)(mu-O)(2)](2+). After
      dehydration in He, Cu-ZSM-5 shows stable NO decomposition activity and the in
      situ XAFS data indicate the formation of a large fraction of the bis(mu
      oxo)dicopper core during reaction. When the Cu/Al ratio of Cu-ZSM-5 exceeds 0.2,
      both the bis(mu-oxo)dicopper core is formed and the NO decomposition activity
      increases sharply. On the basis of the in situ measurements, a reaction cycle is
      proposed in which the bis(mu-oxo)dicopper core forms the product O(2) on a single
      active site and realizes the continuous O(2) release and concomitant self
      reduction.

PMID- 12812506
TI  - Zirconocene-catalyzed propene polymerization: a quenched-flow kinetic study.
AB  - The kinetics of propene polymerization catalyzed by ansa-metallocenes were
      studied using quenched-flow techniques. Two catalyst systems were investigated,
      (SBI)ZrMe2/Al(i)Bu3/[Ph3C][CN[B(C6F5)3]2] (1:100:1) at 25.0 degrees C and
      (SBI)ZrCl(2)/methylalumoxane at 40.0 degrees C (Al:Zr = 2400:1) (SBI = rac
      Me(2)Si(1-Indenyl)2). The aims of the study were to address fundamental
      mechanistic aspects of metallocene-catalyzed alkene polymerizations, catalyst
      initiation, the quantitative correlation between catalyst structure and the rate
      of chain propagation, and the nature of dormant states. One of the most important
      but largely unknown factors in metallocene catalysis is the distribution of the
      catalyst between dormant states and species actively involved in polymer chain
      growth. Measurements of polymer yield Y versus reaction time t for propene
      concentrations [M] = 0.15-0.59 mol L(-1) and zirconocene concentrations in the
      range [Zr] = (2.38-9.52) x 10(-5) mol L(-1) for the borate system showed first
      order dependence on [M] and [Zr]. Up to t approximately 1 s, the half-life of
      catalyst initiation is comparable to the half-life of chain growth; that is, this
      phase is governed by non-steady-state kinetics. We propose a rate law which takes
      account of this and accurately describes the initial rates. Curve fitting of Y(t)
      data provides an apparent chain growth rate constant k(p)(app) on the order of
      10(3) L mol(-1) s(-1). By contrast, the evolution with time of the number-average
      polymer molecular weight, which is independent of the concentration of catalyst
      involved, leads to a k(p) which is an order of magnitude larger, (17.2 +/- 1.4) x
      10(3) L mol(-1) s(-1). The ratio k(p)(app)/k(p) = 0.08 indicates that under the
      given conditions only about 8% of the total catalyst is actively engaged in chain
      growth at any one time. The system (SBI)ZrCl(2)/methylalumoxane is significantly
      less active, k(p)(app) = 48.4 +/- 2.7 and k(p) = (6 +/- 2) x 10(2) L mol(-1) s(
      1), while, surprisingly, the mole fraction of active species is essentially
      identical, 8%. Evidently, the energetics of the chain growth sequence are
      strongly modulated by the nature of the counteranion. Increasing the
      counteranion/zirconium ratio from 1:1 to 20:1 has no influence on catalyst
      activity. These findings are consistent with a model of closely associated ion
      pairs throughout the chain growth sequence. For the borate system, propagation is
      approximately 6000 times faster than initiation, while for the MAO catalyst,
      k(p)/k(i) approximately 800. Polymers obtained at 25 degrees C show 0.1-0.2 mol %
      2,1-regioerrors, and end-group analysis identifies 2,1-misinsertions as the main
      cause for chain termination (66%), as compared to 34% for the vinylidene end
      groups. The results suggest that 2,1-regioerrors are a major contributor to the
      formation of dormant species, even at short reaction times.

PMID- 12812507
TI  - Iron chelation properties of an extracellular siderophore exochelin MN.
AB  - The coordination chemistry of an extracellular siderophore produced by
      Mycobacterium neoaurum, exochelin MN (ExoMN), is reported along with its pK(a)
      values, Fe(III) and Fe(II) chelation constants, and aqueous solution speciation
      as determined by spectrophotometric and potentiometric titration techniques.
      Exochelin MN is of particular interest as it can efficiently transport iron into
      pathogenic M. leprae, which is responsible for leprosy, in addition to its own
      parent cells. The Fe(III) coordination properties of ExoMN are important with
      respect to understanding the Fe(III) acquisition and uptake mechanism in
      pathogenic M. leprae, as the siderophores from this organism are very difficult
      to isolate. Exochelin MN has two hydroxamic acid groups and an unusual threo-beta
      hydroxy-l-histidine available for Fe(III) chelation. The presence of threo-beta
      hydroxy-l-histidine gives rise to a unique mode of Fe(III) coordination. The
      pK(a) values for the two hydroxamic acid moieties, the histidine imidazole ring
      and the alkylammonium groups on ExoMN, correspond well with the literature values
      for these moieties. Proton-dependent Fe(III)- and Fe(II)-ExoMN equilibrium
      constants were determined using a model involving sequential protonation of the
      Fe(III)- and Fe(II)-ExoMN complexes. These data were used to develop a model
      whereby deprotonation reactions on the surface of the complex in the second
      coordination shell result in first coordination shell isomerization. The overall
      formation constants were calculated: log beta(110) = 39.12 for Fe(III)-ExoMN and
      16.7 for Fe(II)-ExoMN. The calculated pFe value of 31.1 is one of the highest
      among all siderophores and their synthetic analogues and indicates that ExoMN is
      thermodynamically capable of removing Fe(III) from transferrin. The E(1/2) for
      the Fe(III)ExoMN/Fe(II)ExoMN(-) couple was determined to be -595 mV from quasi
      reversible cyclic voltammograms at pH = 10.8, and the pH-dependent E(1/2) profile
      was used to determine the Fe(II)-ExoMN protonation constants.

PMID- 12812508
TI  - Magnetic properties of cationic tungsten(IV) half sandwich compounds:
      experimental and theoretical study of a solvent and ligand stabilized singlet
      ground state leading to a thermally induced singlet-triplet spin state
      interconversion.
AB  - A series of novel neutral tungsten(III) and cationic tungsten(IV) complexes with
      disubstituted 4,4'-R,R-2,2'-bipyridyl (R(2)-bpy) ligands of the type [CpW(R(2)
      bpy)Cl(2)](n+) (n = 0,1) were prepared and characterized by X-ray
      crystallography. Susceptibility measurements of the tungsten(IV) complexes
      revealed an intrinsic paramagnetism of these compounds and evidenced different
      magnetic properties of the dimethylamino and methyl (R = NMe(2), Me) substituted
      tungsten(IV) compounds in solution and in the solid state. In dichloromethane
      solution, singlet ground states with thermally populated triplet states were
      observed, whereas triplet (R = Me) and singlet ground states (R = NMe(2)) were
      observed in the solid state. Using both experimental and theoretical techniques
      (DFT) allowed to establish solvation and ligand effects to account for the
      different magnetic behavior. Thermodynamic parameters were derived for the spin
      equlibria in solution by fits of the temperature dependent (1)H NMR shifts to the
      Van Vleck equation and were found to be in excellent agreement with the DFT
      calculations.

PMID- 12812509
TI  - Correlated ab initio study of nucleic acid bases and their tautomers in the gas
      phase, in a microhydrated environment and in aqueous solution. guanine:
      surprising stabilization of rare tautomers in aqueous solution.
AB  - Altogether eight keto and enol tautomers of guanine were studied theoretically in
      the gas phase, in a microhydrated environment (1 and 2 water molecules) and in
      bulk water. The structures of isolated, as well as mono- and dihydrated tautomers
      were determined by means of the RI-MP2 method using the extended TZVPP
      (5s3p2d1f/3s2p1d) basis set. The relative energies of isolated tautomers included
      the correction to higher correlation energy terms evaluated at the CCSD(T)/aug-cc
      pVDZ level. The relative enthalpies at 0 K and relative free energies at 298 K
      were based on the above-mentioned relative energies and zero-point vibration
      energies, temperature-dependent enthalpy terms and entropies evaluated at the
      MP2/6-31G level. The keto form having hydrogen atom at N7 is the global minimum
      while the canonical form having hydrogen atom at N9 represents the first local
      minimum at all theoretical levels in vacuo and in the presence of 1 and 2 water
      molecules. All three unusual rare tautomers having hydrogens at N3 and N7, at N3
      and N9, and also at N9 and N7 are systematically considerably less stable and can
      be hardly detected in the gas phase. The theoretical predictions fully agree with
      existing theoretical as well as experimental results. The effect of bulk solvent
      on the relative stability of guanine tautomers was studied by self-consistent
      reaction field and molecular dynamics free energy calculations using the
      thermodynamic integration method. Bulk solvent, surprisingly, strongly favored
      these three rare tautomers over all remaining low-energy tautomers and probably
      only these forms can exist in water phase. The global minimum (tautomer with
      hydrogens at N3 and N7) is by 13 kcal/mol more stable than the canonical form
      (3rd local minimum). Addition of one or two water molecules does not change the
      relative stability order of isolated guanine tautomers but the respective trend
      clearly supports the surprising stabilization of three rare forms.

PMID- 12812510
TI  - 2D-NMR strategy dedicated to the analysis of weakly ordered, fully deuterated
      enantiomers in chiral liquid crystals.
AB  - Methods for the assignment of the quadrupolar doublets in the deuterium NMR
      spectra of weakly ordered, perdeuterated or partially deuterated enantiomers
      dissolved in chiral liquid crystals are described which use robust 2D correlation
      NMR experiments. To overcome a lack of resolution in deuterium tilted Q-COSY 2D
      spectra in such materials, we propose and explore a correlation 2D sequence which
      is based on deuterium-carbon 2D correlation spectroscopy. The technique results
      in a (13)C-(2)H contour plot and allows the full resonance assignment of
      overcrowded deuterium 1D spectra using carbon-deuterium correlations. The (2)H
      autocorrelation and (13)C-(2)H correlation experiments are applied in the case of
      a racemic mixture of 2-ethylhexanoic acid-d(15) dissolved in a polypeptidic
      chiral oriented solvent. The performance and the limits of both techniques are
      presented and discussed. For the last step of the assignment procedure, we
      propose a simple method for obtaining two coherent sets of quadrupolar
      splittings, one for each enantiomer.

PMID- 12812511
TI  - Fluorine-NMR experiments for high-throughput screening: theoretical aspects,
      practical considerations, and range of applicability.
AB  - Competition ligand-based NMR screening experiments have recently been introduced
      to overcome most of the problems associated with traditional ligand-based NMR
      screening. Molecules with marginal solubility and high affinity for a given
      target can be easily identified in a high-throughput manner by screening chemical
      mixtures against the target in the presence of a weak- to medium-affinity ligand
      of known binding constant. While the original competition-based approaches
      utilized (1)H detection, significant advantages are obtained using (19)F
      detection. The absence of spectral overlap permits the screening of large
      chemical mixtures and allows for automated analysis of the spectra, even in the
      presence of protonated buffers, solvents, and detergents. The large chemical
      shift anisotropy of fluorine and the significant exchange contribution allow for
      the selection of a weak-affinity spy molecule, thus resulting in a lower binding
      affinity threshold for the identified NMR hits. The method, labeled FAXS
      (fluorine chemical shift anisotropy and exchange for screening) is rapid and
      requires only a limited amount of protein and, therefore, compares favorably with
      the other established non-NMR techniques used in high-throughput screening.
      Herein the theoretical aspects of this powerful (19)F-based approach are
      presented and discussed in detail. The experimental conditions together with the
      detection limits and binding constant measurements are investigated using human
      serum albumin as the target.

PMID- 12812512
TI  - Charge-transfer mechanism for cytochrome c adsorbed on nanometer thick films.
      Distinguishing frictional control from conformational gating.
AB  - Using nanometer thick tunneling barriers with specifically attached cytochrome c,
      the electron-transfer rate constant was studied as a function of the SAM
      composition (alkane versus terthiophene), the omega-terminating group type
      (pyridine, imidazole, nitrile), and the solution viscosity. At large electrode
      reactant separations, the pyridine terminated alkanethiols exhibit an exponential
      decline of the rate constant with increasing electron-transfer distance. At short
      separations, a plateau behavior, analogous to systems involving -COOH terminal
      groups to which cytochrome c can be attached electrostatically, is observed. The
      dependence of the rate constant in the plateau region on system properties is
      investigated. The rate constant is insensitive to the mode of attachment to the
      surface but displays a significant viscosity dependence, change with spacer
      composition (alkane versus terthiophene), and nature of the solvent (H(2)O versus
      D(2)O). Based on these findings and others, the conclusion is drawn that the
      charge-transfer rate constant at short distance is determined by polarization
      relaxation processes in the structure, rather than the electron tunneling
      probability or large-amplitude conformational rearrangement (gating). The
      transition in reaction mechanism with distance reflects a gradual transition
      between the tunneling and frictional mechanisms. This conclusion is consistent
      with data from a number of other sources as well.

PMID- 12812513
TI  - Influence of media and homoconjugate pairing on transition metal hydride
      protonation. An IR and DFT study on proton transfer to CpRuH(CO)(PCy3).
AB  - The interaction of the ruthenium hydride complex CpRuH(CO)(PCy(3)) (1) with
      proton donors HOR of different strength was studied in hexane and compared with
      data in dichloromethane. The formation of dihydrogen-bonded complexes (2) and ion
      pairs stabilized by hydrogen bonds between the dihydrogen ligand and the anion
      (3) was observed. Kinetics of the interconversion from 2 to 3 was followed at
      different (CF(3))(3)COH concentrations between 200 and 240 K. The activation
      enthalpy and entropy values for proton transfer from the dihydrogen-bonded
      complex 2 to the (eta(2)-H(2))-complex 3 (DeltaH() = 11.0 +/- 0.5 kcal/mol and
      DeltaS() = -19 +/- 3 eu) were obtained for the first time. The results of the DFT
      study of the proton transfer process, taking CF(3)COOH and (CF(3))(3)COH as a
      proton donors and introducing solvent effects in the calculation with the PCM
      method, are presented. The role of homoconjugate pairs [ROHOR](-) in the
      protonation is analyzed by means of the inclusion of an additional ROH molecule
      in the calculations. The formation of the free cationic complex
      [CpRu(CO)(PCy(3))(eta(2)-H(2))](+) is driven by the formation of the
      homoconjugated anionic complex [ROHOR](-). Solvent polarity plays a significant
      role stabilizing the charged species formed in the process. The theoretical study
      also accounts for the dihydrogen release and production of CpRu(OR)(CO)(PCy(3)),
      observed at temperatures above 250 K.

PMID- 12812515
TI  - Electro-oxidation of carbon monoxide on well-ordered Pt(111)/Sn surface alloys.
AB  - The electro-oxidation of CO on model platinum-tin alloy catalysts has been
      studied by ex-situ electrochemical measurements following the preparation of the
      Pt(111)/Sn(2x2) and Pt(111)/Sn(radical3 x radical3)R30 degrees surfaces. A
      surface redox couple, which is associated with the adsorption/desorption of
      hydroxide on the Sn sites, is observed at 0.28 V(RHE)/0.15 V(RHE) in H(2)SO(4)
      electrolyte on both surfaces. Evidence that it is associated with the adsorption
      of OH comes from ex-situ photoemission measurements, which indicate that the Sn
      atoms are in a metallic state at potentials below 0.15 V(RHE) and an oxidized
      state at potentials above 0.28 V(RHE). Specific adsorption of sulfate anions is
      not associated with the surface process since there is no evidence from
      photoemission of sulfate adsorption, and the same surface couple is observed in
      the HClO(4) electrolyte. CO is adsorbed from solution at 300 K, with saturation
      coverages of 0.37 +/- 0.05 and 0.2 +/- 0.05 ML, respectively. The adsorbed CO is
      oxidatively stripped at the potential coincident with the adsorption of hydroxide
      on the tin sites, viz., 0.28 V(RHE). This strong promotional effect is
      unambiguously associated with the bifunctional mechanism. The Sn-induced
      activation of water, and promotion of CO electro-oxidation, is sustained as long
      as the alloy structure remains intact, in the potential range below 0.5 V(RHE).
      The results are discussed in the light of the requirements for CO-tolerant
      platinum-based electrodes in hydrogen fuel cell anode catalysts and catalysts for
      direct methanol electro-oxidation.

PMID- 12812514
TI  - Theoretical modeling of enzyme catalytic power: analysis of "cratic" and
      electrostatic factors in catechol O-methyltransferase.
AB  - A comparative theoretical study of a bimolecular reaction in aqueous solution and
      catalyzed by the enzyme catechol O-methyltransferase (COMT) has been carried out
      by a combination of two hybrid QM/MM techniques: statistical simulation methods
      and internal energy minimizations. In contrast to previous studies by other
      workers, we have located and characterized transition structures for the reaction
      in the enzyme active site, in water and in a vacuum, and our potential of mean
      force calculations are based upon reaction coordinates obtained from features of
      the potential energy surfaces in the condensed media, not from the gas phase. The
      AM1/CHARMM calculated free energy of activation for the reaction of S-adenosyl
      methionine (SAM) with catecholate catalyzed by COMT is 15 kcal mol(-1) lower the
      AM1/TIP3P free-energy barrier for the reaction of the trimethylsulfonium cation
      with the catecholate anion in water at 300 K, in agreement with previous
      estimates. The thermodynamically preferred form of the reactants in the
      uncatalyzed model reaction in water is a solvent-separated ion pair (SSIP).
      Conversion of the SSIP into a contact ion pair, with a structure resembling that
      of the Michaelis complex (MC) for the reaction in the COMT active site, is
      unfavorable by 7 kcal mol(-1), largely due to reorganization of the solvent. We
      have considered alternative ways to estimate the so-called "cratic" free energy
      for bringing the reactant species together in the correct orientation for
      reaction but conclude that direct evaluation of the free energy of association by
      means of molecular dynamics simulation with a simple standard-state correction is
      probably the best approach. The latter correction allows for the fact that the
      size of the unit cell employed with the periodic boundary simulations does not
      correspond to the standard state concentration of 1 M. Consideration of MC-like
      species allows a helpful decomposition of the catalytic effect into
      preorganization and reorganization phases. In the preorganization phase, the
      substrates are brought together into the MC-like species, either in water or in
      the enzyme active site. In the reorganization phase, the roles of the enzymic and
      aqueous environments may be compared directly because reorganization of the
      substrate is about the same in both cases. Analysis of the electric field along
      the reaction coordinate demonstrates that in water the TS is destabilized with
      respect to the MC-like species because the polarity of the solute diminishes and
      consequently the reaction field is also decreased. In the enzyme, the electric
      field is mainly a permanent field and consequently there is only a small
      reorganization of the environment. Therefore, destabilization of the TS is lower
      than in solution, and the activation barrier is smaller.

PMID- 12812516
TI  - Nucleation of hexagonal ice (Ih) in liquid water.
AB  - The process by which supercooled fluids form stable, crystalline solids has been
      found to be elusive both experimentally and via computer simulations. This is
      because this process, generally called nucleation, is statistical in nature and
      because the set of intermediate states, generally called the critical nucleus, is
      very short-lived. Thus, there are very large uncertainties in even the limited
      experimental data that exist, and computer simulations that have been performed
      can yield descriptive information at best. Here we present a detailed and
      quantitatively accurate observation of the most important nucleation process, the
      freezing of liquid water at ambient conditions. We have accomplished this by
      using a method based on choosing a suitable set of order parameters to
      characterize the crystallinity of the system and a non-Boltzmann sampling Monte
      Carlo approach to obtain a statistical average of the properties of the system
      during its transition from liquid to ice (Ih). We have characterized the order of
      the system statistically at intermediate states between liquid water and ice Ih
      and in so doing described the nucleation process.

PMID- 12812517
TI  - A message from Professor Parviz A Shamlou.

PMID- 12812518
TI  - Exaggerated postprandial lipaemia and lower post-heparin lipoprotein lipase
      activity in middle-aged men.
AB  - An exaggerated postprandial lipaemic response is thought to play a central role
      in the development of an atherogenic lipoprotein phenotype, a recognized lipid
      risk factor for coronary heart disease. A small number of limited studies have
      compared postprandial lipaemia in subjects of varying age, but have not
      investigated mechanisms underlying age-associated changes in postprandial
      lipaemia. In order to test the hypothesis that impaired lipaemia in older
      subjects is associated with loss of insulin sensitivity, the present study
      compared the postprandial lipaemic and hormone responses for 9 h following a
      standard mixed meal in normolipidaemic healthy young and middle-aged men.
      Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were determined in
      post-heparin plasma 9 h postprandially and on another occasion under fasting
      conditions. Postprandial plasma glucose (P<0.02), retinyl ester (indirect marker
      for chylomicron particles; P<0.005) and triacylglycerol (TAG)-rich lipoprotein
      (density<1.006 g/ml fraction of plasma) TAG (P<0.05) and retinyl ester (P<0.005)
      responses were higher in middle-aged men, whereas plasma insulin responses were
      lower in this group (P<0.001). Fasting and 9 h postprandial LPL and HL activities
      were also significantly lower in the middle-aged men compared with the young men
      (P<0.006). In conclusion, the higher incremental postprandial TAG response in
      middle-aged men than young men was attributed to the accumulation of dietary
      derived TAG-rich lipoproteins (density<1.006 g/ml fraction of plasma) and
      occurred in the absence of marked differences in fasting TAG levels between the
      two groups. Fasting and postprandial LPL and HL activities were markedly lower in
      middle-aged men, but lack of statistical associations between measures of insulin
      response and post-heparin lipase activities, as well as between insulin and
      measures of postprandial lipaemia, suggest that this lower activity cannot be
      attributed to lack of sensitivity of lipases to activation by insulin.
      Alternatively, post-heparin lipase activities may not be good markers for the
      insulin-sensitive component of lipase that is activated postprandially.

PMID- 12812519
TI  - Human salivary MUC7 mucin peptides: effect of size, charge and cysteine residues
      on antifungal activity.
AB  - We have previously shown that MUC7 (human salivary low-molecular-mass mucin) 20
      mer: LAHQKPFIRKSYKCLHKRCR (residues 32-51 of the parent MUC7, with a net positive
      charge of 7) possesses a broad-spectrum antimicrobial activity [Bobek and Situ
      (2003) Antimicrob. Agents Chemother. 47, 645-652]. The aims of the present study
      were to determine the minimum peptide chain length and its location within the 20
      mer region that retains potent antifungal activity against Candida albicans and
      Cryptococcus neoformans and to examine the effect of net charge of the peptide as
      well as the role of cysteine residues on the fungicidal activity. First, several
      C-terminal truncated MUC7 20-mer fragments (16-mer, 12-mer, 11-mer, 10-mer and 8
      mer) and one N-terminal fragment (8-mer-N) were synthesized and tested. The
      results showed that MUC7 12-mer, located at the C-terminal region of MUC7 20-mer,
      having a net charge of +6 and exhibiting an amphipathic helical conformation, not
      only retained but exceeded the antifungal activity of that of 20-mer. Secondly,
      several variants of the 12-mer peptide containing a lower or no net positive
      charge, or no cysteine residues were synthesized and tested. A clear correlation
      between the net positive charge of the 12-mer, its potency and initial
      interaction of peptide with fungal cells was found by killing assays,
      fluorescence microscopy and fungal cell-membrane potential measurements.
      Furthermore, cysteine residues, which play a critical role in bacterial binding,
      were found to be not important for the fungicidal activity of these peptides.
      These results identified MUC7 12-mer as a potential candidate for development
      into a novel antifungal therapeutic agent.

PMID- 12812520
TI  - Binding of endostatin to endothelial heparan sulphate shows a differential
      requirement for specific sulphates.
AB  - Endostatin is a naturally occurring proteolytic fragment of the C-terminal domain
      of collagen XVIII. It inhibits angiogenesis by a mechanism that appears to
      involve binding to HS (heparan sulphate). We have examined the molecular
      interaction between endostatin and HS from micro- and macrovessel endothelial
      cells. Two discrete panels of oligosaccharides were prepared from metabolically
      radiolabelled HS, using digestion with either heparinase I or III, and then
      examined for their endostatin affinity using a sensitive filter-binding assay.
      Two types of endostatin-binding regions were identified: one comprising sulphated
      domains of five or more disaccharides in length, enriched in 6-O-sulphate groups,
      and the other contained long heparinase I-resistant fragments. In the latter
      case, evidence from the present study suggests that the binding region
      encompasses a sulphated domain fragment and a transition zone of intermediate
      sulphation. The contribution to binding of specific O-sulphate groups was
      determined using selectively desulphated HS species, namely HS from Hs2st-/-
      mutant cells, and by comparing the compositions of endostatin-binding and non
      binding oligosaccharides. The results indicate that 6-O-sulphates play a dominant
      role in site selectivity and 2-O-sulphates are not strictly essential.

PMID- 12812521
TI  - Suppression by polycyclic compounds of the conversion of human amylin into
      insoluble amyloid.
AB  - There is a significant correlation between the occurrence of pancreatic islet
      amyloid and beta-cell failure in advanced type II diabetes mellitus. Islet
      amyloid is composed primarily of the fibrillar form of the pancreatic hormone,
      amylin. Using thioflavin-T fluorescence binding and radioprecipitation assays, we
      investigated whether or not a series of small tricyclic compounds, tetracycline
      or Congo Red could interfere with the conversion of synthetic human amylin into
      its insoluble amyloid form. Of the compounds investigated, incubation of human
      amylin with a 20-fold molar excess of either Congo Red or Acridine Orange
      resulted in significant inhibition in the rate of amyloid formation. With Congo
      Red, maximal inhibition effectively occurred at a 1:1 molar ratio or greater over
      human amylin, whereas inhibition by Acridine Orange was dose-dependent. A 20-fold
      molar excess of the compound tetracycline also decreased insoluble amyloid
      content after extended incubation periods of approx. 20 h. Amyloid fibril
      morphology in the presence of tetracycline, as measured by transmission electron
      microscopy, was characterized by short fragmented fibrils compared with the
      longer and denser appearance of fibrils formed by amylin alone. These findings
      show that polycyclic compounds can suppress the formation of amyloid by human
      amylin, providing support for an alternative approach to peptide-based strategies
      by which islet amyloid formation could be modulated.

PMID- 12812522
TI  - Enhancement of integrin-mediated transfection of haematopoietic cells with a
      synthetic vector system.
AB  - The aim of the present study was to develop and assess an integrin-targeted
      synthetic vector system for the transfection of haematopoietic cell lines and
      dendritic cells. The vector consists of a cationic liposome, Lipofectin (L), a
      peptide that both targets integrins and binds to DNA (I) and plasmid DNA (D).
      These components interact electrostatically to form the LID vector complex.
      Transfection conditions were optimized for the ratio of vector components, the
      amount of DNA and transfection incubation time. The kinetic analysis of transgene
      expression revealed a peak of activity at about 24 h, followed by a rapid decline
      over the next 48 h. Targeted gene delivery was demonstrated by comparing
      transfected luciferase reporter gene levels using LID complexes containing
      integrin-targeting peptide sequences with a control peptide. In addition,
      transfection levels of integrin-targeted LID complexes were significantly
      enhanced by treatment of cells with PMA, which was also shown to activate
      integrin receptors and enhance binding to fibronectin. Under optimized conditions
      transfection efficiencies of 19% for TF-1 cells, 28% for Jurkat cells and 10% for
      primary dendritic cells were achieved. The LID vector may thus find application
      for gene-transfer experiments in haematopoietic cell lines and for the
      development of genetic vaccines using transfected dendritic cells.

PMID- 12812524
TI  - Association of adenoma and focal nodular hyperplasia: experience of a single
      French academic center.
AB  - BACKGROUND: We report our experience of the simultaneous occurrence of adenoma
      and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was
      found in five out of 30 cases of "multiple benign hepatocytic nodules" collected
      in our files of the Department of Pathology of the University Hospital of
      Bordeaux, during the last 12 years. All five cases were women on oral
      contraceptives. In all cases, the reason for surgery was the discovery, by
      imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor,
      possibly an adenoma. RESULTS: Four cases of FNH were discovered by imaging
      techniques, prior to surgery. Additional small nodules were diagnosed either
      during surgery or during the slicing of the specimen in 3 cases. Adenoma and the
      FNH cases identified by imaging techniques were confirmed as such by light
      microscopy. Some small nodules could not be categorized with certainty because
      they contained biliary structures without ductular reaction. In one case, the non
      nodular liver was abnormal around the area in which there were multiple nodules:
      there was approximation of portal tracts with portal and hepatic venous
      thromboses, and portal tract remnants with arteries surrounded with a rim of
      fibrosis. In two cases, some large hepatic veins had thickened walls.
      CONCLUSIONS: The association of FNH and adenoma could be coincidental or
      secondary to shared causal mechanisms: a) systemic and local angiogenic
      abnormalities induced by oral contraceptives; b) tumor-induced growth factors; c)
      thrombosis and local arterio-venous shunting. A better recognition of the
      association of adenoma and FNH, particularly in the context of multiple nodules,
      could be useful in clinical practice.

PMID- 12812523
TI  - Low-dose adenosine stress echocardiography: detection of myocardial viability.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic potential of low
      dose adenosine stress echocardiography in detection of myocardial viability.
      BACKGROUND: Vasodilation through low dose dipyridamole infusion may recruit
      contractile reserve by increasing coronary flow or by increasing levels of
      endogenous adenosine. METHODS: Forty-three patients with resting dyssynergy, due
      to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110
      mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for
      myocardial viability was improvement in systolic thickening of dyssinergic
      segments of >or= 1 grade at follow-up. Coronary angiography was done in 41 pts.
      Twenty-seven patients were revascularized and 16 were medically treated.
      Echocardiographic follow up data (12 +/- 2 months) were available in 24
      revascularized patients. RESULTS: Wall motion score index improved from rest 1.55
      +/- 0.30 to 1.33 +/- 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments
      with baseline dyssynergy, adenosine echocardiography identified 122 segments as
      positive for viability, and 135 as necrotic since no improvement of systolic
      thickening was observed. Follow-up wall motion score index was 1.31 +/- 0.30 (p <
      0.001 vs. rest). The sensitivity of adenosine echo test for identification of
      viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%.
      Positive and negative predictive values were 97% and 80%, respectively.
      CONCLUSION: Low-dose adenosine stress echocardiography test has high diagnostic
      potential for detection of myocardial viability in the group of patients with
      left ventricle dysfunction due to previous myocardial infarction. Low dose
      adenosine stress echocardiography may be adequate alternative to low-dose
      dobutamine test for evaluation of myocardial viability.

PMID- 12812525
TI  - Vendor-to-vendor education to improve malaria treatment by private drug outlets
      in Bungoma District, Kenya.
AB  - BACKGROUND: Private outlets are the main suppliers of uncomplicated malaria
      treatment in Africa. However, they are so numerous that they are difficult for
      governments to influence and regulate. This study's objective was to evaluate a
      low-cost outreach education (vendor-to-vendor) programme to improve the private
      sector's compliance with malaria guidelines in Bungoma district, Kenya. The
      cornerstone of the programme was the district's training of 73 wholesalers who
      were equipped with customized job aids for distribution to small retailers.
      METHODS: Six months after training the wholesalers, the programme was evaluated
      using mystery shoppers. The shoppers posed as caretakers of sick children needing
      medication at 252 drug outlets. Afterwards, supervisors assessed the outlets'
      knowledge, drug stocks, and prices. RESULTS: The intervention seems to have had a
      significant impact on stocking patterns, malaria knowledge and prescribing
      practices of shops/kiosks, but not consistently on other types of outlets. About
      32% of shops receiving job aids prescribed to mystery shoppers the approved first
      line drug, sulfadoxine-pyremethamine, as compared to only 3% of the control
      shops. In the first six months, it is estimated that 500 outlets were reached, at
      a cost of about $8000. CONCLUSIONS: Changing private sector knowledge and
      practices is widely acknowledged to be slow and difficult. The vendor-to-vendor
      programme seems a feasible district-level strategy for achieving significant
      improvements in knowledge and practices of shops/kiosks. However, alternate
      strategies will be needed to influence pharmacies and clinics. Overall, the
      impact will be only moderate unless national policies and programmes are also
      introduced.

PMID- 12812526
TI  - The unique ethical challenges of conducting research in the rehabilitation
      medicine population.
AB  - BACKGROUND: The broad topic of research ethics is one which has been relatively
      well-investigated and discussed. Unique ethical issues have been identified for
      such populations as pediatrics, where the issues of consent and assent have
      received much attention, and obstetrics, with concerns such as the potential for
      research to cause harm to the fetus. However, little has been written about
      ethical concerns which are relatively unique to the population of patients seen
      by the practitioner of rehabilitation medicine. DISCUSSION: This paper reviews
      unique ethical concerns in conducting research in this population, including
      decision-making capacity, communication, the potential for subject overuse, the
      timing of recruitment, hope for a cure and therapeutic misconception and the
      nature of the health care provider-research subject relationship. SUMMARY:
      Researchers in the area of rehabilitation medicine should be aware of some of the
      unique ethical challenges posed by this patient population and should take steps
      to address any potential concerns in order to optimize subject safety and ensure
      that studies meet current ethical guidelines and standards.

PMID- 12812527
TI  - Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.
AB  - BACKGROUND: Renal impairment is one of the predictors of mortality in cardiac
      surgery. Usually a binarized value of serum creatinine is used to assess the
      renal function in risk models. Creatinine clearance can be easily estimated by
      the Cockcroft and Gault equation from serum creatinine, gender, age and body
      weight. In this work we examine whether this estimation of the glomerular
      filtration rate can advantageously replace the serum creatinine in the EuroSCORE
      preoperative risk assessment. METHODS: In a group of 8138 patients out of a total
      of 11878 patients, who underwent cardiac surgery in our hospital between January
      1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be
      determined and logistic regression analysis performed. In all patients scored,
      creatinine clearance was calculated according to Cockcroft and Gault. The
      relationship between the predicted and observed 30-days mortality was evaluated
      in systematically selected intervals of creatinine clearance and significance
      values computed by employing Monte Carlo methods. Afterwards, risk scoring was
      performed using a continuous or a categorical value of creatinine clearance
      instead of serum creatinine. The predictive ability of several risk score models
      and the individual contribution of their predictor variables were studied using
      ROC curve analysis. RESULTS: The comparison between the expected and observed 30
      days mortalities, which were determined in different intervals of creatinine
      clearance, revealed the best threshold value of 55 ml/min. A significantly higher
      30-days mortality was observed below this threshold and vice versa (both with p <
      0.001). The local adaptation of the EuroSCORE is better than the standard
      EuroSCORE and was further improved by replacing serum creatinine (SC) by
      creatinine clearance (CC). Differential ROC analysis revealed that CC is superior
      to SC in providing predictive power within the logistic regression. Variable rank
      comparison identified CC as the best single variable predictor, even better than
      the variable age, former number 1, and SC, previously number 9 in the standard
      set of EuroSCORE variables. CONCLUSION: The renal function is an important
      determinant of mortality in heart surgery. This risk factor is not well captured
      in the standard EuroSCORE risk evaluation system. Our study shows that creatinine
      clearance, calculated according to the Cockcroft and Gault equation, should be
      applied to estimate the preoperative renal function instead of serum creatinine.
      This predictor variable replacement gains a significant improvement in the
      predictive accuracy of the scoring model.

PMID- 12812528
TI  - A novel BDNF gene promoter directs expression to skeletal muscle.
AB  - BACKGROUND: Cell-specific expression of the gene that encodes brain-derived
      neurotrophic factor (BDNF) is required for the normal development of peripheral
      sensory neurons and efficient synaptic transmission in the mature central and
      peripheral nervous system. The control of BDNF gene expression involves multiple
      tissue and cell-specific promoters that are differentially regulated. The
      molecular mechanisms that are responsible for tissue and cell-specific expression
      of these promoters are still incompletely understood. RESULTS: The cloning and
      analysis of three additional zebrafish (Danio rerio) BDNF gene exons and two
      associated promoters, is reported. Among them are two exons that generate a novel
      tripartite mature transcript. The exons were located on the transcription unit,
      whose overall organization was determined by cloning, Southern blot hybridization
      and sequence analysis, and compared with the pufferfish (Fugu rubripes) and
      mammalian BDNF loci, revealing a conserved but more compact organization.
      Structural and functional analysis of the exons, their adjacent promoters and 5'
      flanks, showed that they are expressed cell-specifically. The promoter associated
      with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5'
      flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene
      containing the promoter and 1.5 KB of 5' flank is directed exclusively to
      skeletal muscle of transiently transfected embryos. The second promoter, whose
      associated 5' exon contains a 25-nucleotide segment of identity with a mammalian
      BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR
      analysis of total RNA from whole juvenile fish and adult female skeletal muscle
      revealed tissue-specific expression of the 5' exons but the novel exon could not
      be detected even after two rounds of nested PCR. CONCLUSION: The zebrafish BDNF
      gene is as complex as the mammalian gene yet much more compact. Its exons are
      expressed in an independently regulated and cell-specific fashion. An initial
      structural and functional analysis has shown that the regions controlling
      zebrafish BDNF gene expression have been cloned and identified. They can now be
      subjected to detailed molecular and genetic analyses to identify the cellular
      mechanisms by which the transcription factors that act on these regions control
      BDNF gene expression.

PMID- 12812529
TI  - TMC and EVER genes belong to a larger novel family, the TMC gene family encoding
      transmembrane proteins.
AB  - BACKGROUND: Mutations in the transmembrane cochlear expressed gene 1 (TMC1) cause
      deafness in human and mouse. Mutations in two homologous genes, EVER1 and EVER2
      increase the susceptibility to infection with certain human papillomaviruses
      resulting in high risk of skin carcinoma. Here we report that TMC1, EVER1 and
      EVER2 (now TMC6 and TMC8) belong to a larger novel gene family, which is named
      TMC for trans membrane channel-like gene family. RESULTS: Using a combination of
      iterative database searches and reverse transcriptase-polymerase chain reaction
      (RT-PCR) experiments we assembled contigs for cDNA encoding human, murine, puffer
      fish, and invertebrate TMC proteins. TMC proteins of individual species can be
      grouped into three subfamilies A, B, and C. Vertebrates have eight TMC genes. The
      majority of murine TMC transcripts are expressed in most organs; some
      transcripts, however, in particular the three subfamily A members are rare and
      more restrictively expressed. CONCLUSION: The eight vertebrate TMC genes are
      evolutionary conserved and encode proteins that form three subfamilies.
      Invertebrate TMC proteins can also be categorized into these three subfamilies.
      All TMC genes encode transmembrane proteins with intracellular amino- and
      carboxyl-termini and at least eight membrane-spanning domains. We speculate that
      the TMC proteins constitute a novel group of ion channels, transporters, or
      modifiers of such.

PMID- 12812530
TI  - Asymptomatic bacteriuria in institutionalized elders in Israel.
AB  - OBJECTIVES: To document the prevalence of asymptomatic bacteriuria in patients in
      one large long-term care facility, and describe clinical outcomes in initially
      bacteriuric and nonbacteriuric residents during prospective observation
      encompassing one year. METHODS: Patients enrolled in the study were residents of
      the Haim-Shoham Geriatric Center, a long-term care institute with 800
      inhabitants. Twenty patients were related randomly for study enrollment on each
      of the ten wards. A urine culture was obtained from the enrolled patients. A
      second culture was obtained within one week if the initial culture grew >or=
      10(5) colony-forming units per milliliter (cfu/ml) of at least one uropathogen.
      Demographic data and comorbidities, as well as most recent laboratory results,
      were recorded for all patients enrolled. Subjects were followed prospectively for
      one year or until death. Clinical events and usage of antibiotics were recorded.
      In patients with asymptomatic bacteriuria, repeated urine cultures were obtained
      every two months. RESULTS: Eighty-five (43.3%) of a total of 196 elder residents
      screened presented asymptomatic bacteriuria. There were no differences between
      patients with and without asymptomatic bacteriuria in age, gender, and underlying
      diseases. Patients with asymptomatic bacteriuria were significantly more bed
      ridden (91.7% vs. 82.1%, P = 0.05); demented (78.8% vs. 59.8%, P = 0.03); and
      incontinent of urine (93% vs. 71.4%, P < 0.0001) and bowel (85.8% vs. 59.3%).
      During one year of prospective observation, bacteriuric patients had a mortality
      rate of 25.9%, compared to 7.1% for nonbacteriuric (P < 0.0001). Mortality in the
      group with bacteriuria was higher due to both urinary infection and other causes.
      CONCLUSIONS: In our population, asymptomatic bacteriuria was associated with
      increased functional impairment and increased mortality over 12 months. The
      increased mortality, however, was not fully attributable to urinary infection.

PMID- 12812531
TI  - Development of definitions for acute illness in nursing home residents based on
      chart-recorded physical exam findings.
AB  - OBJECTIVES: To develop and test simple, chart-based criteria for acute illness in
      nursing home residents for clinical and epidemiological study. DESIGN:
      Observational study. SETTING: A 409-bed not-for-profit nursing home.
      PARTICIPANTS: 102 custodial care residents. MEASUREMENTS: Physical exam findings
      commonly performed in nursing home residents were used to define 10 acute
      conditions. Residents were observed prospectively to test the clinical relevance
      of these definitions. Episodes of acute illness satisfying definition criteria
      were identified, as well as treatment changes, hospitalizations, and deaths.
      RESULTS: During a median follow-up of 60 days, 43 acute illnesses occurred,
      affecting 30 (29%) residents. Of these episodes, 77% were associated with
      treatment changes, hospitalization, or death. The new definitions captured 79% of
      all episodes of acute illness. The most common diagnoses were urinary tract
      infection, lower respiratory infection, and gastroenteritis/gastrointestinal
      upset. Independent risk factors for acute illness were gastrostomy feeding,
      depression, and history of fracture. CONCLUSIONS: Acute illness in the nursing
      home is common and frequently associated with treatment changes, hospitalization
      and death. It can be identified using a small number of chart-recorded physical
      exam-based findings as criteria.

PMID- 12812532
TI  - Sputum bacteriology in nursing home pneumonia: a retrospective study.
AB  - INTRODUCTION: Pneumonia is the most lethal infection in nursing homes. The
      Infectious Disease Society of America recommends that attempts be made to obtain
      quality sputum to focus antibiotic therapy. This is especially important within
      the enclosed space of a nursing home, where constant pressure from broad
      spectrum, empiric antibiotics sets the stage for the emergence of resistant
      organisms. METHODS: We reviewed all cases of radiographic pneumonia diagnosed on
      site at the Wisconsin Veterans Home, a 721-bed facility, for the recording of
      sputum bacteriology and 30-day mortality. RESULTS: Ninety-nine cases of
      radiographic pneumonia diagnosed on-site were identified over 1 year. Mortality
      was 10% within 30 days. Fourteen quality sputum specimens were obtained and
      processed microbiologically. None of the individuals who had a sputum specimen
      died within 30 days, probably because the ability to obtain a sputum specimen is
      a marker of higher functional status. DISCUSSION: Even if empiric therapy
      continues in the majority of cases, cultures in individual cases may alert
      clinicians to noncovered, resistant pathogens, and allow focused antibiotic
      therapy with agents like amoxicillin that might extend the usefulness of empiric,
      broad spectrum antibiotics. Institutions may also sum the results of sputum
      bacteriology to assist in the choice of empiric antibiotic therapy. Sputum
      bacteriology may benefit both the individual resident and the entire population
      of the institution.

PMID- 12812533
TI  - Calcium and vitamin D supplementation in nursing home residents.

PMID- 12812534
TI  - Are all pressure ulcers avoidable?
AB  - A quality of care debate centers on whether pressure ulcers result from factors
      largely dependent on caregivers, or whether pressure ulcers result from factors
      associated with patient morbidity. A reduction in incidence, defined as the
      development of a new pressure ulcer, is the focus of prevention strategies. Yet
      epidemiological data demonstrates a stability in the incidence of pressure ulcers
      despite drastic improvements in understanding of pressure ulcers, increased
      regulatory oversight, and improvements in technologies available for prevention
      of pressure ulcers. The explanation for this stable incidence of pressure ulcers
      includes a failure of known effective preventive treatment to be applied or the
      failure of prevention strategies to be effective in spite of being applied. No
      intervention strategy has been reported that consistently and reproducibly
      reduces the incidence of pressure ulcers to zero. The published data on
      prevention of pressure ulcers do not support an assumption that all pressure
      ulcers are preventable. An effective prevention strategy demonstrated to
      eliminate pressure ulcers across healthcare settings is lacking.

PMID- 12812535
TI  - Preliminary evaluation of a convalescence cardiac unit for older patients as a
      model of "transitional facility" from hospital to home.
AB  - OBJECTIVES: The increasing number of older cardiac patients combined with the
      tendency to reduce hospital stays created the need for a Convalescence Cardiac
      Unit (Con.CU). It functions as a transitional facility for elderly patients
      discharged from hospitals after cardiac events, and was established within a
      geriatric medical center using existing infrastructure and staff. METHODS:
      Patients from 5 neighboring general hospitals (including 23 internal medicine
      wards and 3 departments of cardiac surgery) were offered the option of one week
      stay in the Con.CU after discharge. During the stay in the unit they received
      medical supervision as well as counsel on matters of nutrition and physical
      activity. RESULTS: 78 patients were admitted during the first 14 months. Forty
      patients were after coronary artery bypass grafts (CABG) (51%)30 after acute
      myocardial infarction (MI) (38%). The average age was 75 +/- 2.5 (SD). Medical
      complications developed in 57%. Most of these patients were treated by the local
      staff. Five cases had to be readmitted to the hospital they came from. Elderly
      cardiac patients that chose the option of Con.CU and their families expressed
      high appreciation regarding this experience and its contribution in facilitating
      return home. CONCLUSION: This innovative model is aimed to improve continuity of
      care for elderly cardiac patients and provide them with a new service in this era
      of "early discharge" from hospitalization. Geriatric settings striving to
      diversify their services, and medical directors required to contribute to policy
      development may learn from this experience.

PMID- 12812536
TI  - Choosing appropriate medical care for the elderly.
AB  - Decisions about what constitutes appropriate medical care are increasingly
      necessary in an aging society. Neither patient autonomy, physician beliefs, nor
      health services research alone can adequately define reasonable care for the
      individual patient. A new framework is proposed for determining reasonable
      medical care that involves 4 steps: (1) patients prioritize their goals of care
      (prolongation of life, maintenance of function, and maximization of comfort); (2)
      physicians assign a pathway of care based on the patient's prioritization of
      goals (longevous, ameliorative, or palliative); (3) expert panels define a range
      of feasible interventions for each pathway; and (4) medical problems are treated
      with interventions consistent with the pathway chosen. The pathway system has the
      potential for defining reasonable care by balancing the patient's view, the
      physician's view, and evidence from the clinical literature.

PMID- 12812537
TI  - CPT codes: the evolution and current state of codes and their use.

PMID- 12812538
TI  - Implementing pressure ulcer prevention and treatment programs: using AMDA
      Clinical Practice Guidelines.

PMID- 12812539
TI  - The specialist training program for nursing home physicians: a new professional
      challenge.

PMID- 12812540
TI  - The greatest gift.

PMID- 12812541
TI  - The downstream financial effects of a nursing home practice on an academic
      medical center.
AB  - OBJECTIVE: To determine the financial impact of a nursing home practice on an
      academic medical center. DESIGN: Retrospective cohort design. SETTING: Middle
      sized Midwestern community with fee-for-service Medicare population. SAMPLE: One
      hundred seventy-six nursing home residents followed by faculty and residents of a
      medical school department of family and community medicine. MEASUREMENTS:
      Billings and collections for professional and hospital services delivered by the
      academic medical center during fiscal year 1998. RESULTS: One hundred forty-four
      patient-years of service resulted in over 1 million dollars in billed charges.
      For every 1 dollar billed by family medicine, consulting physicians billed 2
      dollars and the hospital billed 10 dollars. This amounted to over 4000 dollars
      per patient per year in reimbursement. This practice generated a wide variety of
      clinical problems (37 different diagnosis-related groups (DRGs) for the 61
      admissions to the hospital). CONCLUSIONS: There is a significant downstream
      financial effect of a nursing home practice on an academic health center. For
      this and other reasons, this practice may be worthy of institutional support.

PMID- 12812542
TI  - Implementation of a nursing home urinary incontinence management program with and
      without tolterodine.
AB  - OBJECTIVE: To evaluate the implementation of a nursing home urinary incontinence
      management program. DESIGN: A prospective field trial of the program
      incorporating practice guidelines and principles of continuous quality
      improvement. SETTING: Five nursing homes in New York, Virginia, and Georgia
      PARTICIPANTS: One hundred fifty-one residents identified as being incontinent of
      urine and who met inclusion criteria for ongoing participation in the program.
      INTERVENTION: Key multidisciplinary staff from the five nursing homes were
      trained in the program and assumed responsibility for implementing it in their
      facilities. The program consisted of a clinical assessment, toileting protocols,
      and the addition of the antimuscarinic drug tolterodine in selected residents who
      did not respond well to toileting alone. Data on dryness rates during the 60-day
      toileting protocols, collected by nursing home staff, were analyzed on a weekly
      basis by an overall project coordinator who sent data back to the nursing homes
      in an easy-to-read graphical format. MEASURES: (1) The dryness rate, defined as
      the number of times the resident was dry divided by the number of times the
      resident was checked (every 2 hours from 7 a.m. to 7 p.m.); and (2) adverse
      events (eg, dry mouth, increased confusion, need for dosage reduction). RESULTS:
      Of 645 residents in the 5 nursing homes, 377 (58%) were identified as incontinent
      of urine, of whom 151 (40%) were placed on an ongoing toileting program. Of these
      151 residents, 48 (32%) were prescribed tolterodine, and 117 (78%) completed the
      60-day trial. The initial dryness rate was 57%, and for the group as a whole
      remained essentially unchanged (increase in dryness 1%, P = 0.50). Among 50
      clinically stable residents on a toileting program alone, the increase in the
      dryness rate was 16% (P = 0.001), and for 31 clinically stable residents
      prescribed tolterodine, the increase in the dryness rate was 29% (P = 0.012). Two
      residents had their dosage of tolterodine reduced because of dry mouth and
      nausea,one resident was taken off the drug because of increased pain in the back
      and legs and increased confusion. CONCLUSIONS: Overall, this program resulted in
      significant increases in dryness rates for clinically stable incontinent nursing
      home residents. These residents represented 22% of the total number of residents
      identified as incontinent in the five participating nursing homes. Tolterodine
      was prescribed for approximately one-third of incontinent residents as a
      supplement to a toileting program, and was well tolerated. Nursing homes should
      be encouraged to implement similar urinary incontinence programs, target
      toileting protocols to the most responsive residents, and maintain the program
      using principles of continuous quality improvement.

PMID- 12812543
TI  - The nursing home resident with a history of pedophilia: issues and challenges.

PMID- 12812544
TI  - Will nurse practitioners replace physicians as attendings in long-term care?

PMID- 12812545
TI  - A club of friends: enrolling nursing home residents in an adult day program.
AB  - OBJECTIVE: To evaluate an innovative approach to maintaining physical, cognitive,
      and social functioning in frail, elderly nursing home residents at risk for
      transfer from a minimal care unit. SUBJECTS/SETTING: Nineteen Russian-speaking
      residents of the Jewish Home in San Francisco who were newly enrolled in an on
      site adult day care program. METHODS: A formal evaluation of the program employed
      a repeated measures design with assessments at baseline and at Months 2, 3, 4, 6,
      and 9. Outcomes included stability of living situation, functional status,
      physical and mental health, cognitive functioning, sense of well-being and
      quality of life, and satisfaction with the program. RESULTS: During this period,
      the cohort was medically stable and, although some evidenced cognitive decline,
      there was little change in their functional status. Nearly all of the residents
      reported improvement from baseline in some aspects of their lives, with the
      greatest proportions reporting positive changes in social support and quality of
      life. CONCLUSIONS: Findings from this evaluation suggest that activities
      programming using the model described here may enhance the quality of life for
      some nursing home residents and enable them to remain in the least restrictive,
      as well as the least costly, living situation possible.

PMID- 12812546
TI  - Evaluation of vitamin B12 and folate status in the nursing home.

PMID- 12812547
TI  - Severe adverse effects of aggressive opioid therapy in chronic nonmalignant pain.

PMID- 12812548
TI  - Multi-cultural issues in advance directives.

PMID- 12812550
TI  - When the nursing home resident with advanced dementia stops eating: what is the
      medical director to do?

PMID- 12812549
TI  - Practice guideline for evaluation of Fever and infection in long-term care
      facilities.

PMID- 12812551
TI  - An overview of home health care in Israel.

PMID- 12812552
TI  - Lessons learned.

PMID- 12812553
TI  - Involuntary weight loss, wound healing, and optimal nutritional intervention.

PMID- 12812554
TI  - Management of psychosis and agitation in elderly patients with dementia: a
      comprehensive approach.

PMID- 12812555
TI  - Depression in the long-term care patient: new tools for evaluation and treatment.

PMID- 12812556
TI  - Reducing the risk of cardiovascular complications in the long-term care setting.

PMID- 12812557
TI  - Alzheimer's disease in long-term care: maximizing treatment options.

PMID- 12812558
TI  - Thrombotic complications in the acute medically ill: update for the medical
      director.

PMID- 12812559
TI  - Comparing and contrasting the atypical antipsychotics: a data-driven focus on
      differentiation.

PMID- 12812560
TI  - Identifying and managing GERD in the elderly: optimizing therapy and improving
      outcomes.

PMID- 12812562
TI  - Reduce polypharmacy and boost appropriate drug use.

PMID- 12812561
TI  - Better dental care needed for nursing facility residents.

PMID- 12812564
TI  - End-of-life decision-making: myths versus options.

PMID- 12812563
TI  - Reducing falls in the nursing home.

PMID- 12812565
TI  - Medical observation yields useful clinical clues.

PMID- 12812566
TI  - What medical directors should know about front-line caregivers.

PMID- 12812567
TI  - Nonpharmacologic interventions help patients with dementia.

PMID- 12812568
TI  - Centers for Medicare and Medicaid Services and State Survey Officials Woo Medical
      Directors.

PMID- 12812569
TI  - Improving the quality of nurse assistants in nursing homes: report of an
      attending physician survey and an AMDA Symposium.
AB  - OBJECTIVES: To describe views of attending physicians regarding nurse assistants
      as part of a multidisciplinary seminar on nurse assistants at the 1997 American
      Medical Directors Association (AMDA) Annual Symposium. DESIGN: Mailed survey.
      PARTICIPANTS: AMDA members. MEASUREMENTS: Attitudes regarding nurse assistants
      and the role of attending physicians with regard to enhancing the role of nurse
      assistants. RESULTS: Respondents rated the importance of quality nurse assistants
      with a mean of 4.85 and a mode of 5 (5 being very important). They also thought
      it was important for the medical director attending physicians to support, train,
      or otherwise assist in the professional development of nurse assistants (mean
      4.07, mode 5). Respondents recommended enhanced training, reduced workload,
      increased salary and benefits, and building more effective relationships as
      strategies for improving the quality of care provided by nurse assistants.
      CONCLUSION: Physicians can be important in enhancing the role of the nursing
      assistant. Some activities may include acknowledging the nurse assistant,
      providing support and feedback, and supporting policy changes that enhance
      continuity, nonhierarchical management, and creative training programs.

PMID- 12812570
TI  - Differentiating between lewy body dementia and Alzheimer's disease: a
      retrospective brain bank study.
AB  - Recent research has shown that while Lewy body dementia. (LBD) may be the second
      most common form of dementia, it is difficult to confirm the disease before
      autopsy. Patients with LBD share many clinical signs and symptoms with patients
      diagnosed with Alzheimer's disease (AD), making it difficult to differentiate
      between the two diseases in patients who are still living. Still, our purpose in
      this study was to determine any clinical features which may differentiate between
      autopsy-confirmed cases of AD and cases of LBD. We compared 13 patients with
      autopsy-confirmed AD with 12 patients who had autopsy-confirmed LBD. Phone calls
      were made to family members of the deceased to help clarify and add any other
      information not documented in the patient's files. Significant differences were
      found in three areas, and trends approaching statistical significance were found
      in two other areas. Visual hallucinations were more prominent in the patients
      with LBD than in the patients with AD (10/12 LBD vs. 4/13 AD, P < 0.05). A
      nonspecific tremor was also found more often in the LB patients than in the
      Alzheimer's patients (8/12 LBD vs. 3/13 AD, P < 0.05). Finally, the LB patients
      were more prone to wandering, especially earlier in the disease course than were
      the patients with AD (10/12 LBD vs. 6/13 AD, P < 0.5). There was also a trend
      within the LB patients for higher use of anxiolytics (9/12 LBD vs. 6/13 AD, P =
      0.14) as well as antidepressants (7/12 LBD vs. 4/13 AD, P = 0.16). Our data
      confirmed our hypothesis that LBD from a clinical perspective is indeed similar
      to AD. However, the higher incidence of visual hallucinations, tremor and
      wandering as well as the trend toward the use of anxiolytics and antidepressants
      among LB patients was noted. This gives hope that a clinical differentiation
      between these two diseases and more specific treatments may be possible in the
      future.

PMID- 12812571
TI  - Assessment of constipation management in long-term care patients.
AB  - OBJECTIVES: To determine the prevalence of diagnosed constipation among nursing
      home patients; to assess the prevalence of routine (at least one time per week
      for 4 consecutive weeks) laxative use; and to investigate prescribing practices.
      DESIGN: A retrospective multi-center medical record evaluation. SETTING: Any one
      of 25 nursing facilities representative of a long-term care pharmaceutical
      provider's geographical coverage. PARTICIPANTS: All patients under the age of 65,
      and/or who had resided in the facility for less than 4 weeks, and/or who were
      placed in a specialty care bed (eg, Alzheimer's disease, hospice, HIV/AIDS) were
      excluded. RESULTS: A total of 712 resident charts meeting initial inclusion
      criteria were screened, 392 (55%) of which had a documented diagnosis of
      constipation and/or routine laxative use. Approximately 28% (CI +/- 3.3) of
      residents had a documented diagnosis of constipation. The rate of laxative use
      within the same sample population of 712 patients was 53.8% (CI +/- 3.7). Of the
      392 patients with a diagnosis of constipation and/or routine laxative use, over
      72% had at least one diagnosis or medication known to precipitate constipation.
      The most commonly prescribed laxatives were stool softeners (26.2%), saline
      laxatives (18.4%) and stimulant/irritant laxatives (15.6%). Almost half of the
      laxative users were prescribed more than one agent. CONCLUSION: This study
      supports the concern that there is often a gap between documentation of symptoms
      and constipation treatment decisions. No correlation was found between the
      specific laxative prescribed and the presence or absence of a documented
      diagnosis of constipation. Treatment decisions should be based on thorough
      examination and individualized patient needs. Furthermore, there is a need to
      increase monitoring for drug effectiveness.

PMID- 12812572
TI  - Criminal and civil liability of physicians for institutional elder abuse and
      neglect.

PMID- 12812573
TI  - Drug-related hyperthermia.
AB  - The elderly are prone to disorders of thermoregulation. Hyperthermia, an
      elevation of core temperature, occurs as a result of several causes in older
      subjects. The elderly, particularly in nursing homes, are often prescribed
      multiple medications. Physiological changes with aging and the use of numerous
      predisposing drugs can contribute to disorders of temperature regulation.
      Presented is a dramatic case of drug- related hyperthermia in a nursing home
      resident with an adverse outcome in spite of recognition and treatment of the
      disorder.

PMID- 12812574
TI  - Aide for a day.
AB  - The author worked for an 8-hour shift in the role of nursing assistant at a
      skilled nursing facility as an additional provider over and above the usual
      staffing. The purpose of this exercise was (1) to demonstrate to nursing
      assistants the respect of administration for their work, (2) to gain firsthand
      insights into the specific tasks they perform, and (3) to describe potential
      inefficiencies and barriers to providing care. Following the shift, the author
      provided a written report to the administrator and the director of nursing
      describing the shift and making clinical and programmatic recommendations.

PMID- 12812575
TI  - Quality improvement case study: issues involving an attending physician's
      obligation to document physical exam findings in nursing home residents.

PMID- 12812576
TI  - Commentary on the quality improvement case study.

PMID- 12812577
TI  - Delivery of nutrition and hydration care in nursing homes: assessment and
      interventions to prevent and treat dehydration, malnutrition, and weight loss.

PMID- 12812579
TI  - Defining common ground: long term care financing reform in 2001.

PMID- 12812578
TI  - Recognizing physical abuse and neglect in the skilled nursing facility: the
      physician's responsibilities.

PMID- 12812580
TI  - Improving rates of advance directive discussions among managed care nursing home
      enrollees.
AB  - BACKGROUND: Discussions about advance directives should be offered to all nursing
      home residents. Managed Medicare programs for nursing home residents allow for
      the development of performance improvement initiatives to ensure that these
      discussions occur and are documented. PURPOSE: To assess the effectiveness of an
      intervention to increase discussion and documentation of advance directives for
      enrollees in a managed Medicare program for nursing home residents, and to
      evaluate whether this intervention affected preferences for cardiopulmonary
      resuscitation (CPR) and hospitalization among enrollees. SUBJECTS: Participants
      were 4,248 enrollees in a managed Medicare program in 1996, and 6,598 enrollees
      in 1997, in Georgia, Maryland, Massachusetts, Minnesota, Arizona, and Florida.
      DESIGN: Descriptive study of a quality improvement initiative. METHODS: A chart
      review was conducted in the fall of 1996 to determine the prevalence of
      documented advance directive discussions among all enrollees, and the preferences
      regarding CPR and hospitalization. Because the discussion rates varied across
      sites, and were lower than expected, each site developed strategies to improve
      advance directive discussion and documentation. One year later, a similar survey
      was conducted to determine the efficacy of the interventions, as well as to
      assess the impact, if any, on rates of desire for CPR and hospitalization.
      RESULTS: Documented discussions of advance directives increased across the six
      sites from 73% to 85% (P < 0.001). The overall percentage of patients desiring
      CPR did not change following the intervention (18%). However, there were
      geographical differences in the desire for CPR among enrollees, with those in
      Minnesota (8%), Arizona (11%), and Florida (12%) desiring it the least, and those
      in Massachusetts (20%), Georgia (29%), and Maryland (29%) desiring it the most.
      The overall percentage of desire for hospitalization decreased from 65% to 62% (P
      < 0.001). Enrollees in Georgia were most likely to want hospitalization (87%),
      and enrollees in Minnesota were the least likely to want hospitalization (57%).
      CONCLUSIONS: In a managed care program, documentation of advance directive
      discussions can be increased with focused efforts. Overall, most enrollees did
      not desire CPR, but a majority desired hospitalization. Despite the similarity of
      interventions and program philosophy across sites, significant geographic
      variations in desire for CPR and hospitalization remained.

PMID- 12812581
TI  - The Functional Pain Scale: reliability, validity, and responsiveness in an
      elderly population.
AB  - OBJECTIVES: Because of difficulty experienced in assessing pain in frail older
      patients and the lack of pain assessment tools with standardization in the
      elderly, the Functional Pain Scale (FPS), an instrument incorporating both
      subjective and objective components to assess pain, was developed and evaluated.
      DESIGN, SETTING, PARTICIPANTS, AND MEASURES: One hundred subjects more than 65
      years old participated in the validity, reliability, and responsiveness (the
      clinical sensitivity of the instrument to change) testing of the Functional Pain
      Scale. Subjects were recruited from a geriatrics inpatient setting, a geriatrics
      outpatient setting, and a local hospice (residing in their homes). Ninety-four of
      the subjects completed all phases of testing. Reliability was tested using a test
      retest format and a correlation matrix. Criterion-related validity was
      established as compared with the Visual Analog Scale (VAS), the Present Pain
      Intensity (PPI), the McGill Short Form Questionnaire (MPQ-SF), and the Numeric
      Pain Scale (NPS) instruments. Responsiveness for the FPS, the VAS, the PPI, the
      MPQ-SF, and the NPS instruments was determined using five previously described
      techniques: effect size, standardized response means, relative efficiency, direct
      comparison of t test scores, and direct comparison of P values. A cumulative
      index was developed to rank each scale. Cumulative responsiveness index scores
      were based on individual scale performance for each separate responsiveness test.
      The lowest score in the cumulative responsiveness index indicated the most
      responsive scale. RESULTS: Interrater reliability for instruments tested exceeded
      0.95 for all instruments tested. Validity testing showed high correlations as
      well (r = 0.62, r = 0.85, r = 0.80, r = 0.90 for the VAS, the PPI, the MPQ-SF,
      and the NPS respectively). Responsiveness evaluated overall by the responsiveness
      index was best for the Functional Pain Scale (7) followed by the Visual Analog
      Scale (12), the Present Pain Intensity (13), the McGill Pain Questionnaire-Short
      Form (19), and the Numerical Pain Questionnaire (24). CONCLUSIONS: The Functional
      Pain Scale was determined to be reliable, valid, and responsive. The
      responsiveness of the Functional Pain Scale was superior to the other instruments
      tested. The Functional Pain Scale is an acceptable instrument for assessing pain
      in older adults and may reflect changes in pain better than other instruments
      tested. Further testing in other populations is warranted.

PMID- 12812582
TI  - Outcome in ambulatory status immediately following hip fracture surgery in the
      acute setting: a comparison of nursing home residents and community older adults.
AB  - OBJECTIVE: To compare the ambulatory status following hip fracture surgery in the
      acute setting between older adults from long-term care facilities (LTCF) and the
      community. SETTING: A 650-bed, urban, inner city, university-affiliated teaching
      hospital. METHODS: One hundred forty hip fracture patients (60-97 years) from
      long-term care facilities and the community were examined. Ambulatory status
      before and after surgery was categorized four ways based on the degree of
      independence in ambulation: A1 = independent ambulation (with or without an
      assisting device), A2 = assistance of another person required, A3 = predominant
      use of a wheelchair, and A4 = bed-bound. Change in ambulatory status was
      designated as "moderate" if the deterioration was one status level only (A1 to
      A2, A2 to A3, and A3 to A4) or "major" if the deterioration was more than one
      status level (A1 to A3/A4 or A2 to A4). Additional variables such as age, sex,
      risk factors, length of stay, history of drug use, and laboratory results also
      were examined. RESULTS: Hip fracture patients from LTCF were older (P = 0.0160)
      and had more overall risk factors for hip fracture (P = 0.0039) than community
      patients. They also had higher rates of dementia (P < 0.000), arrhythmia (P =
      0.025), delirium (P = 0.0016) and anxiolytics use (P = 0.019) than patients from
      the community. On admission, LTCF patients had lower serum calcium (P = 0.0003),
      phosphorus (P = 0.0210), and albumin (P = 0.0004) than community patients. Before
      hospitalization they also were less ambulatory (P = 0.002) than community
      patients. Post surgery, ambulatory status declined in both groups. However, a
      "major" change (decline) in ambulatory status occurred more often in LTCF
      patients (P = 0.001). CONCLUSIONS: A greater decline in ambulatory status is seen
      in patients from LTCF than in community patients, immediately following hip
      fracture surgery. Compared with community patients, LTCF patients are also older,
      sicker (higher total risk score) and have an increased risk for a decline in
      functional status.

PMID- 12812583
TI  - Fully integrated complementary care in a nursing facility.

PMID- 12812586
TI  - Bridge building, not rain dancing: a medical director's core management
      responsibilities.

PMID- 12812584
TI  - Issues involving a consultant's obligation to nursing home residents.

PMID- 12812587
TI  - The implications of the Benefits Improvement and Protection Act (BIPA) 2000 for
      long-term care.

PMID- 12812589
TI  - Effect of local conjugated estrogens on vaginal pH in elderly women.
AB  - OBJECTIVE: The decline in estrogens during and after menopause is associated with
      an increase in vaginal pH and an increased susceptibility to urinary tract
      infections (UTIs). Decreased vaginal pH following short-term treatment with
      topical estrogens may reduce the incidence of such infections. This study was
      undertaken to evaluate the effect of low-dose, topical conjugated estrogens
      vaginal cream (CEVC) on vaginal pH in older, postmenopausal women. DESIGN: We
      conducted a retrospective analysis of initial and follow-up evaluations of older,
      postmenopausal women residing in 19 long-term care facilities who were referred
      to Seton Health System's Incontinence Treatment Center between January 2, 1997,
      and June 13, 1998. Patients were untreated or were administered conjugated
      estrogens intravaginally (0.5 g/d, 3 days per week). SETTING: Incontinence
      Treatment Center, Seton Health System. PARTICIPANTS: Two hundred fifty-eight
      postmenopausal women (mean age 83 years), residents of skilled nursing
      facilities, who were diagnosed with urinary incontinence, were included in the
      study. MEASUREMENTS: Measurements included age, CEVC treatment, vaginal pH, and
      history of UTIs or hysterectomy. RESULTS: In the CEVC-treated women, vaginal pH
      was reduced from a mean of 7.41 +/- 0.71 to 6.80 +/- 0.70 after 6 weeks (n = 213;
      P = 0.0001). No differences in vaginal pH were observed in untreated women (n =
      45). Continuation of CEVC treatment for an additional 6 weeks (n = 93) resulted
      in further decreases in vaginal pH (P = 0.017). Women who discontinued treatment
      after 6 weeks maintained a lower vaginal pH for 6 weeks (P = 0.0004), and there
      was no significant difference between groups at Week 12. CONCLUSIONS: Low-dose
      CEVC for 6 and 12 weeks reduces vaginal pH in older women residing in long-term
      care facilities. The decreased vaginal pH following short-term treatment with
      topical estrogens may reduce the incidence of recurrent UTIs.

PMID- 12812590
TI  - Elderly African-Americans and the influenza vaccine: the impact of the primary
      care physician.
AB  - BACKGROUND: Despite recommendations for annual vaccinations against influenza,
      many older African-Americans do not receive this vaccine. For 1 month in our
      private medical offices, we conducted a survey to estimate the vaccination rate
      for our practice, the reasons why older African-Americans declined to be
      vaccinated, and any impact we could make on their misconceptions about its safety
      and efficacy. SETTING: The study was conducted in a three-physician private
      practice of geriatric/internal medicine in the borough of Queens, New York.
      PARTICIPANTS: 231 consecutive community-residing patients aged 65 or older were
      evaluated starting in October 1999. METHODS: A total of 231 patients aged 65 to
      96 were given a questionnaire asking if they planned to or had already received
      the influenza vaccine for the 1999-2000 season. Those who had no intention of
      taking the vaccine were asked why. Categories included: Vaccine not
      recommended/not recommended strongly enough, vaccine has no benefit, I became ill
      after being vaccinated, too afraid, I heard it makes people sick, no special
      reason, allergy to eggs, never had the flu. Those who refused had a brief
      discussion with their physician and it was noted whether they agreed later to be
      vaccinated. Ten patients who were not black were excluded. RESULTS: Forty-four
      percent (98/221) of patients intended to be vaccinated before discussion with
      their physician. After discussion with their physician about potential side
      effects, efficacy,safety, the percentage rose to 63% (139/221). This compares
      favorably with the national health objective of 60% or greater for the year 2000
      in this population. CONCLUSIONS: The primary care physician had a significant
      impact on the increase of the influenza vaccination rate among older African
      Americans in our study from 44 to 63%.

PMID- 12812591
TI  - A comparison of the well-being of family caregivers of elderly patients
      hospitalized with physical impairments versus the caregivers of patients
      hospitalized with dementia.
AB  - OBJECTIVES: This study investigated the differences between the level of well
      being of caregivers of older patients hospitalized with dementia and the well
      being of caregivers of older patients hospitalized with physical impairments. It
      also explored the relationships between social roles, religious faith, and well
      being. SETTING: Two groups were constructed to compare caregivers' well-being
      levels: caregivers of patients with dementia and caregivers of patients with
      physical impairments. The groups were caregivers of patients of two geriatric
      hospitals in central Israel. Patients were categorized by their medical files
      according to their medical diagnosis. PARTICIPANTS: A total of 107 caregivers
      participated in this research. Of that number, 46% were caregivers of patients
      with physical impairments while the other 54% were caregivers of patients with
      dementia. The patients with physical impairments suffered from stroke, hip
      fractures, Parkinson's disease, diabetes, and heart and lung diseases. The
      patients with dementia suffered from Alzheimer's disease or related dementia. Of
      the total number of patients, 67% were males and 33% were females. INTERVENTION:
      The caregivers were asked to fill out a questionnaire that included 90 questions.
      Some of the questionnaires were given to the caregivers to be filled out at home.
      MEASUREMENTS: The questionnaire integrated three subcategories: well-being,
      identity accumulation, and religious faith. RESULTS: Differences were found only
      in the dimensions of social activity. Caregivers of the patients with physical
      impairments were found to attend synagogues and clubs more than caregivers of the
      patients with dementia did. The number of the caregivers' social roles were found
      to have been significantly related to caregivers' mental health. A negative
      correlation was found between the intensity of religious faith and the level of
      the caregivers' spouses' self-rated physical and mental health: those of stronger
      faith rated their physical health lower and were reported to have more symptoms
      of stress. CONCLUSION: There are no significant differences between the level of
      well-being of caregivers of patients with dementia and caregivers of patients
      with physical impairments. Both groups of caregivers are at great risk of
      compromised physical and mental health, of decreased social activity, and of
      financial distresses. Various social roles and religious faith may enhance the
      caregiver's well-being. However, the spouse's religious faith has negative
      effects on their own well-being. These results call for welfare services and
      religious organizations to form support groups for family caregivers. They also
      make clear that all caregivers should benefit from the same social support if
      their older relatives are hospitalized.

PMID- 12812592
TI  - A protocol for status epilepticus in a long-term care facility using rectal
      diazepam (Diastat).
AB  - INTRODUCTION: A growing population of residents in long-term care facilities
      (LTCF) is likely to present with status epilepticus (SE), which requires rapid
      treatment to avoid permanent neuronal damage, associated morbidity, and
      mortality. The treatment of choice for SE is an intravenous benzodiazepine;
      however, this is not feasible in most LTCFs because of the training level of the
      personnel and the risk of respiratory depression. Transport to acute care
      facilities is often delayed and, in addition, many LTCF residents have "do not
      hospitalize" orders. As an alternative to an intravenous benzodiazepine, rectal
      delivery of diazepam has been shown to be effective in stopping prolonged
      seizures and is more easily accomplished in the LTCF setting. METHODS: The Badger
      Prairie Health Care Center (BPHCC), a 132-bed LTCF in Verona, WI, developed a
      protocol for SE that uses a rectal diazepam gel preparation (Diastat) when
      intravenous access is unavailable. The protocol provides for initiation of long
      term anticonvulsant therapy as a follow-up to the acute treatment of SE. RESULTS:
      BPHCC staff successfully employed the protocol eight times from August 1999 to
      November 2000; this article describes the protocol and three representative
      cases.

PMID- 12812593
TI  - Wernicke's encephalopathy: the subacute setting as safety net.
AB  - Wernicke's encephalopathy is a disease forgotten but not gone. In the subacute
      setting, it is likely to appear after a (typically brief) hospital stay requires
      vigilance and skill to diagnose. Treatment with parenteral thiamine, a safe
      intervention, is often successful in reversing the neurological manifestations.
      We argue that the subacute setting is an appropriate setting in which to diagnose
      and treat Wernicke's encephalopathy and that this disease is but one of many for
      which the subacute service will be increasingly responsible.

PMID- 12812594
TI  - Geriatric medicine and primary care groups in England.

PMID- 12812595
TI  - Medication errors and adverse drug events in nursing homes: problems, causes,
      regulations, and proposed solutions.

PMID- 12812596
TI  - Staffing ratios in nursing facilities: where do we stand?

PMID- 12812597
TI  - A 10-year perspective on the patients referred to a geriatric rehabilitation
      complex: the influence of managed care.
AB  - OBJECTIVE: In the past 10 years, HMOs have used managed care to reduce patients
      referrals for rehabilitation in our Geriatric Rehabilitation Complex (GRC).
      DESIGN: This study compares data regarding patients referred for rehabilitation
      for 4 months in 1998 with data from a similar study we performed in 1989.
      SETTING: The GRC, which is part of a 396-bed geriatric hospital, includes a 36
      bed ward complemented by departments of physical and occupational therapy, a
      speech therapy unit, and a rehabilitation psychologist. It is supported by modern
      rehabilitation equipment and facilities and is staffed by experienced, highly
      qualified academic personnel. RESULTS: The overall number of patients referred
      for rehabilitation decreased by 36% during this period. However, the average age
      of patients is higher, the number of patients with Recc. Stroke dominates, and
      length of stay was reduced by 20%. CONCLUSION: Although the rehabilitation needs
      of older people are increasing, fewer patients are referred to our GRC. Those who
      are referred are older, and their condition is more complicated; nevertheless,
      their length of stay has also been reduced. These are the results of HMO policies
      to refer older patients to new "rehabilitation settings" that charge lower prices
      while offering services of still unproved quality. As geriatricians, it is our
      duty to prevent cost considerations from overtaking the need to maximizing
      functional recovery.

PMID- 12812598
TI  - Physician use of and attitudes regarding the minimum data set.
AB  - OBJECTIVE: To determine physician use of the Minimum Data Set (MDS), part of the
      Resident Assessment Instrument (RAI). DESIGN: A population-based survey. SETTING:
      The United States. PARTICIPANTS: A total of 2223 physicians listing geriatrics as
      their primary specialty, 1921 of whom are internists and 302 family physicians.
      MEASUREMENTS: A 34-item questionnaire asking nine physician-specific demographic
      questions; nursing home caseload; percent time spent reviewing MDS and care plan;
      how the information on the MDS was used. Physicians were also asked to describe
      their attitudes about the MDS. RESULTS: Among the 472 physicians who completed
      the survey and cared for nursing home patients, 357 were internists and 107 were
      family physicians. Ninety-one percent of the physicians were board certified, 76%
      had certificate of added qualifications in geriatrics,65% oversaw 20 nursing home
      patients. Only 11% of physicians reported reviewing the entire MDS, and 21% part
      of the MDS for all of their patients. Nineteen percent of physicians did not
      review the care plan for any of their patients. Fifty-six percent of 461 comments
      made by physicians regarding the MDS were negative or derogatory. CONCLUSIONS:
      Many practicing geriatricians are not using MDS to facilitate medical decisions.
      If this physician population is not using the MDS, there is a need to improve the
      information transfer from the MDS form to the busy clinician.

PMID- 12812599
TI  - A cross-national comparison of institutionalized tube-fed older persons: the
      influence of contrasting healthcare systems.
AB  - OBJECTIVE: Different health care settings may influence the type of patients
      selected for long-term tube-feeding. Clinical characteristics of older, tube-fed
      institutionalized subjects living in Ontario, Canada were compared with those in
      the United States (US). DESIGN: A cross-sectional cohort study Setting: Nursing
      homes in the states of Mississippi, Texas, and Vermont (US) and chronic care
      facilities in Ontario. PARTICIPANTS: Tube-fed residents older than age 65 living
      in facilities in the US between January 1, 1996, and March 31, 1997 (n = 859),
      and in institutions in Ontario between January 1, 1996, and December 31, 1997 (n
      = 913). MEASUREMENTS: Data were obtained from Minimum Dataset assessments at both
      sites. Demographic and clinical characteristics were compared between tube-fed
      subjects living in the US and those in Canadian facilities. RESULTS: In a
      logistic regression model, the following characteristics were significantly more
      likely to be found among tube-fed subjects in the US than in those in Ontario:
      greater impairment of cognitive performance, cardiopulmonary disease, a diagnosis
      of dementia, female, and age greater than 80 years. Characteristics that were
      significantly less likely to be present among the US tube-fed subjects included:
      recurrent lung aspirations, a chewing or swallowing problem, do not resuscitate
      status, restraint use, weight loss, and stroke. CONCLUSIONS: Clinical
      characteristics differ between older, institutionalized tube-fed subjects in
      Ontario and in US nursing homes. In order to put these differences into context,
      consideration must be given to how the contrasting healthcare systems in these
      two countries may drive decision-making for long-term tube-feeding.

PMID- 12812600
TI  - Barriers to vision care for nursing home residents.
AB  - OBJECTIVE: To describe the prevalence of periodic eye examinations by eye
      professionals and to examine nursing facility resident characteristics associated
      with lack of periodic screening. DESIGN: Retrospective chart review. SETTING: Two
      Midwestern nursing facilities. PARTICIPANTS: Between 1995 and 1997, 134 subjects
      aged 60 and older were recruited from two metropolitan nursing facilities.
      MEASUREMENTS: Nursing home charts were reviewed for: demographics, length of
      stay, date of eye examination, eye diagnosis,visual acuity. Nursing assessments
      were used to obtain information about cognition, function, behavior, and the
      presence of Do Not Resuscitate or Do Not Hospitalize orders. The chart was
      reviewed for visual acuity, intraocular pressures, and the presence of eye
      pathology. Individuals who had not had eye examinations in the previous 2 years
      were screened by an ophthalmologist. This examination included external
      examination of the eye, fundoscopic examination, tonometry,visual acuity with
      correction. RESULTS: Only 62 (46%) of the subjects had been seen by an eye care
      professional in the previous 2 years. Visual acuity information was available for
      37/64 previously examined subjects. Of those with no eye examination in the
      previous 2 years (n = 72), visual acuity was obtained in 32 (44%) of subjects.
      New eye diagnoses were made in 64% (41/64). Logistic regression models with "eye
      examination within the past 2 years" as the dependent variable show that
      residents who do not desire hospital transfer are 80% less likely to have had an
      eye examination than those without this designation. Sex, age, length of stay,
      functional status, presence of severe dementia, behavior problems, or DNR orders
      do not change the likelihood that a resident would have been examined. Logistic
      regression models with "visual acuity measured" as the dependent variable show
      that residents with severe dementia are 12.6 times less likely to have acuity
      measured than those without dementia. Those with a length of stay in the facility
      less than 6 months are 10% less likely to have visual acuity measured.
      CONCLUSIONS: This study does not confirm that barriers still exist in the
      provision of eye care to all nursing home residents, but the prevalence of such
      assessments remains low. Additional screening results in a substantial increase
      in the identification of treatable eye diseases. Contrary to the original
      hypotheses that patient characteristics that make testing difficult would provide
      a barrier or disincentive to vision testing, this study did not show statistical
      differences in the rates of vision screening for those with dementia, behavior
      problems, or severe functional impairment. Severe dementia does seem to affect
      the ability of the eye care specialist to gather subjective data such as visual
      acuity. It also demonstrates that vision screening does take place on nursing
      home residents with a broad range of cognitive and functional abilities, and this
      screening results in the diagnosis of many treatable eye conditions. Future
      efforts should be made to increase vision screening and treatment in the nursing
      home.

PMID- 12812601
TI  - Successful ECT in long-term care residents.
AB  - INTRODUCTION: Depression is common in long-term care (LTC) residents and causes
      increased mortality and morbidity. Treatment resistance or intolerance to
      antidepressants is not unusual. Electroconvulsive therapy (ECT) is a safe and
      effective alternative for older community-dwelling residents but has not been
      well studied in LTC residents. METHODS: A retrospective chart review was made of
      all LTC residents who received ECT from a single academic 538-bed facility over a
      3-year period. Demographic information, severity of medical illness as measured
      by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), psychiatric
      diagnosis, earlier psychotropic drug trials, and MMSE before and after ECT were
      collected. ECT therapy was reviewed for number and types of treatments and
      complications. Outcome after ECT was rated with the Clinical Global Impression of
      Change scale (CGI). RESULTS: Thirteen patients (4 men, 9 women ), mean age 81
      years (range: 65-95), received ECT. All had a diagnosis of major depression, and
      10 had associated psychotic features. All patients received at least two
      psychotropic agents before receiving ECT (range: 2-11). Patients also had
      significant medical comorbidity, with a mean (CIRS-G) of 19.7 (range: 14-27). On
      average, patients received 5.7 ECT treatments in the hospital (range: 3-10), and
      9 of 13 patients received bilateral stimuli. Nine patients (69%) were rated as
      improved, two (15%) were clinically unchanged, and two (15%) were rated as worse.
      Complications included transient atrial fibrillation in one patient,
      posttreatment headache in one patient, and delirium in one patient. Five patients
      had transient cognitive decline as measured by the MMSE, but all recovered fully
      by 1 month. CONCLUSIONS: ECT was a safe and effective treatment modality in this
      population of LTC residents with a significant medical comorbidity. 69% of
      patients exhibited clinical improvement despite previous medication resistance.
      Careful monitoring for delirium in this population is essential to prevent more
      protracted posttreatment confusion.

PMID- 12812602
TI  - Weight variance associated with atypical neuroleptics in nursing home dementia
      patients.
AB  - OBJECTIVE: Atypical antipsychotics have been reported to cause significant weight
      gain. This study examined potential weight gain associated with the use of
      olanzapine or risperidone. DESIGN: A retrospective chart review. SETTING: Three
      long-term care facilities. PARTICIPANTS: Dementia patients (n = 50) given
      olanzapine or risperidone for the management of noncognitive behavioral
      disturbances. MEASUREMENTS: Weight changes over a 4-month period. RESULTS:
      Overall, patients in both groups lost weight over a 4-month period. Four (16%) of
      the risperidone patients and no olanzapine patients gained more than 5 pounds.
      CONCLUSION: Weight change does not seem to be a significant clinical issue for
      older dementia patients taking low doses of atypical neuroleptics.

PMID- 12812603
TI  - Hypothermia in the nursing home: adverse outcomes in two older men.
AB  - Older people are vulnerable to extreme changes of ambient temperatures caused by
      impaired thermoregulatory function. This results in a high mortality in older
      subjects during increases and decreases in the environmental temperature. From
      1979 through 1994, a total of 11,817 deaths were reported in the United States
      for which hypothermia was the underlying cause (average annual number and rate:
      739 and 0.3 per 100,000 population). Half of these occurred in adults older than
      age 65. For reasons that are unclear, mortality in men was more than double that
      in women (1.8 vs. 0.8). Presented are two cases of hypothermia with adverse
      outcomes in male residents living in long-term care facilities (LTCF).

PMID- 12812604
TI  - Antimicrobial resistance patterns among urine isolates from patients in a
      geriatric hospital and from older patients in a general hospital in Jerusalem.
AB  - INTRODUCTION AND RATIONALE: Urinary tract infection is the most common cause of
      nosocomial infections in patients hospitalized in chronic care facilities. The
      changing spectrum of microorganisms involved in urinary tract infections and the
      emerging resistance require continuous monitoring to provide crucial information
      to guide empirical therapy and encourage prudent use of antibiotics. The aim of
      this survey was to assess the antimicrobial resistance profile of urine isolates
      from patients hospitalized in a geriatric hospital and from elderly patients
      hospitalized in an acute care hospital in order to guide empirical therapy of
      urinary tract infections. METHODS: The survey was performed in two hospitals in
      Jerusalem: a university-affiliated geriatric hospital- Herzog -and an acute
      secondary- and tertiary-care university hospital- Hadassah. We performed a
      retrospective analysis of antimicrobial resistance of all positive urine cultures
      obtained from patients in the geriatric division of Herzog Hospital and from
      patients aged 65 years and older hospitalized in the Internal Medicine
      departments in Hadassah Hospital during a 1-year period. RESULTS: The most common
      bacteria isolated from urine specimens in Herzog Hospital were, in order of
      frequency, Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa. We
      demonstrated a high rate of antimicrobial resistance of those bacteria in both
      hospitals. The pattern we observed necessitates recommending ceftazidime as the
      most appropriate empirical therapy for urinary tract infection in Herzog
      Hospital. In Hadassah Hospital we recommend cefuroxime for those patients in good
      general condition and ceftazidime for those who present with clinical sepsis.
      Antimicrobial resistance patterns should be assessed periodically and
      recommendations modified accordingly. Infection control guidelines should be
      implemented in order to try to decrease the rate of antimicrobial resistance.
      Further research is requested to assess the efficacy of such interventions in
      long-term care facilities.

PMID- 12812605
TI  - Videotaping to protect nursing facility residents: a legal analysis.

PMID- 12812606
TI  - Managed care: managing the elderly.

PMID- 12812607
TI  - Front line workers in long-term care: the effect of educational interventions and
      stabilization of staffing ratios on turnover and absenteeism.
AB  - OBJECTIVE: Front line workers in long-term care play a crucial role in helping
      residents achieve their highest possible functional level. High turnover (rates
      in excess of 100% are common) and absenteeism threaten the ability of long-term
      care providers to meet this goal. The purpose of this study was to determine the
      effect of a formalized certified nursing assistant (CNA) education program and
      stabilization of staffing ratios on turnover and absenteeism. DESIGN AND SETTING:
      This study was a 12-month prospective, nonrandomized trial involving two long
      term care facilities providing traditional intermediate and skilled care serving
      as study sites and a similar facility serving as a control. For historical
      comparisons, each facility served as its own control using data from the year
      before the interventions. INTERVENTIONS: An in-house educational program based on
      the State of North Carolina core curriculum for CNAs was instituted in each study
      site. During the study period, efforts were made to achieve stable staffing
      ratios of 1 CNA:8 residents for days, 1:10 for evenings, and 1:15 for nights.
      Traditional quality of care indicators and resident/surrogate satisfaction were
      tracked during the study period. RESULTS: Both study facilities showed a decline
      in turnover, with the decline reaching statistically significant levels at
      Facility B (134% to 41%, P = 0.0001). Absenteeism rates did not change
      significantly during the study period. Resident/surrogate satisfaction with
      nursing care was improved significantly at Facility B (P = 0.02). CONCLUSION: A
      formal education program in conjunction with stabilization of staffing ratios can
      result in lower turnover rates for CNA's and improved resident/surrogate
      satisfaction.

PMID- 12812608
TI  - Deep vein thrombosis as a complication of megestrol acetate therapy among nursing
      home residents.
AB  - OBJECTIVES: To describe a cluster of cases of proximal deep vein thrombosis among
      nursing home residents treated with megestrol acetate, to identify other risk
      factors for deep vein thrombosis development among these patients, and to alert
      physicians to this potential complication of megestrol acetate therapy. DESIGN:
      Retrospective review. SETTING: A 129-bed Maryland nursing home. PARTICIPANTS:
      Nineteen residents prescribed megestrol acetate between November 1997 July 1998,
      identified by computerized pharmacy records. MEASUREMENTS: Demographic data
      (including identification of known risk factors for deep vein thrombosis
      development) were collected along with information on the indications for
      megestrol acetate therapy and its duration, diagnostic studies related to
      detection of deep vein thrombosis and their results, and patient outcomes
      following diagnosis of deep vein thrombosis. RESULTS: Megestrol acetate was
      prescribed for 18 nutritionally at-risk patients and one with uterine cancer. Six
      (32%) patients developed deep vein thrombosis signs and symptoms, and all
      diagnoses were confirmed as proximal deep vein thromboses with Doppler studies.
      (No diagnosis of deep vein thrombosis were made among any nursing home patients
      not being treated with megestrol acetate during the observation period.) All
      patients diagnosed with deep vein thrombosis were hospitalized and
      anticoagulated, but none were diagnosed with pulmonary embolus or died. The
      length [median (range)] of megestrol acetate treatment was similar regardless of
      whether deep vein thrombosis developed [117 (57-244) versus 143 (2-294) days,
      respectively, P = 0.83]. Stratification by length of treatment in 50-day
      increments revealed that most patients who developed deep vein thrombosis did so
      after 50 days of treatment (P = 0.046). CONCLUSION: A high incidence of deep vein
      thrombosis was identified among nursing home residents treated with megestrol
      acetate, even among ambulatory individuals with no other known risk factors.
      Because the efficacy of megestrol acetate treatment in nursing home residents
      with weight loss is unproven, the risk of deep vein thrombosis must be considered
      when prescribing megestrol acetate, and its use to treat nutritionally at-risk
      nursing home residents should be limited.

PMID- 12812609
TI  - Health status, staffing, and medicaid reimbursement in nursing homes: 1985 to
      1995.
AB  - CONTEXT: Policy changes implemented by Medicaid and Medicare in the early 1980s
      resulted in a functionally more dependent nursing home population. OBJECTIVES:
      This paper contends that (1) staffing in nursing homes has become more efficient;
      (2) nursing home residents are functionally more dependent;(3) Medicaid per diem
      reimbursement is inadequate. DATA SOURCES: Staffing data came from the National
      Nursing Home Facility Survey conducted by the National Center for Health
      Statistics (NCHS) in 1985 and 1995. Functional dependency data, defined as
      assistance with any of six Activities of Daily Living (ADLs), came from the NCHS
      National Nursing Home Current Resident Surveys in 1985 and 1995. Reimbursement
      rates came from the State Medicaid Reimbursement Surveys conducted by the
      University of California at San Francisco to which the Consumer Price Index,
      Hospital and Related Services Item was applied. DATA SYNTHESIS: Administration
      decreased by 4.4 full-time equivalents (FTEs) (80.0%) per 100 beds, whereas
      patient care increased by 8.2 FTEs (18.9%). Residents requiring assistance with
      four or more ADLs increased by 9.9%, and the mean number of ADLs per patient
      increased from 3.9 to 4.3. Applying the Consumer Price Index to the 1984
      reimbursement rate indicated an annual deficit of 5526.00 dollars for each
      Medicaid patient by 1995. CONCLUSIONS: This research strongly supports its
      contentions but fails to demonstrate them conclusively. The data indicate that
      long-term care facilities have reallocated staffing to accommodate the
      requirements of more functionally dependent residents and that Medicaid
      reimbursement has failed to maintain its initial purchasing power.

PMID- 12812610
TI  - Seasonal variation of deaths from fatal myocardial infarction, primary cardiac
      arrest, sudden cardiac death, and refractory congestive heart failure in older
      persons living in New York City.
AB  - OBJECTIVE: To investigate if there is seasonal variation in cardiac deaths in
      older persons living in a nursing home in New York City. DESIGN: In a prospective
      study, the major clinical cause of death of all persons aged 60 years and older
      residing in a nursing home in New York City during a 15-year period was
      investigated. The author carefully reviewed the major cause of death with the
      physicians taking care of all persons who died in the nursing home or after
      transfer to a general hospital. We investigated whether there was seasonal
      variation in deaths from either fatal myocardial infarction, primary cardiac
      arrest, sudden cardiac death, or refractory congestive heart failure. SETTING: A
      large nursing home in which 1265 older persons died of fatal myocardial
      infarction, primary cardiac arrest, sudden cardiac death, or refractory
      congestive heart failure during a 15-year period. PATIENTS: The 1265 persons who
      died from cardiac causes included 410 men and 855 women, mean age 83 +/- 8 years
      at the time of death. MEASUREMENTS AND MAIN RESULTS: During a 15-year period,
      1265 older persons died of fatal myocardial infarction, primary cardiac arrest,
      sudden cardiac death, or refractory congestive heart failure. Cardiac deaths
      occurred from December through March in 497 of 1265 persons (39%), from April
      through July in 378 of 1265 persons (30%), and from August through November in
      390 of 1265 persons (31%). The frequency of cardiac deaths was significantly
      greater between December and March (P < 0.001). The incidence of cardiac deaths
      between December and March was 1.29 times greater than the average of the
      incidence of cardiac deaths during the two other 4-month periods. CONCLUSION: The
      frequency of cardiac deaths in older persons living in a nursing home in New York
      City significantly increased 1.29 times during the period December through March
      compared with the average of the two other 4-month periods (P < 0.001).

PMID- 12812611
TI  - Determination of serum albumin in older adults. A need for specification of the
      assay method.
AB  - OBJECTIVES: To assess the difference between two colorimetric methods for serum
      albumin determination, bromocresol purple (BCP) and bromcresol green (BCG), in
      patients hospitalized in a geriatric hospital. DESIGN: Prospective study of
      consecutive blood samples. SETTING: A 200-bed Geriatric Division of a university
      affiliated geriatric-psychiatric hospital. PARTICIPANTS AND MEASUREMENTS: All
      serum albumin determinations were obtained from patients hospitalized in the
      geriatric division during a 3-month period, November 1999 through January 2000.
      All albumin determinations were performed by two methods: BCP and BCG. RESULTS: A
      total of 326 serum albumin determinations were performed during the study period.
      The average serum albumin levels observed were 28.2+/-7.5 g/L and 37.6+/-7.2 g/L
      for the BCP and BCG methods, respectively. Using the BCP method, 80.1% of serum
      albumin levels were below 35.0 g/L (cutoff point for hypoalbuminemia) versus
      41.1% using the BCG method. CONCLUSIONS: The widespread use of both BCG and BCP
      and the marked clinical implications of their alternative use underscores the
      importance of specifying the method employed in determination of serum albumin in
      routine laboratory analyses. Moreover, physicians need to be aware of which
      procedure is being used in their hospital.

PMID- 12812612
TI  - Insomnia in the long-term care setting: assessment and management.

PMID- 12812613
TI  - Appropriateness of laboratory testing in nursing home elderly with advanced
      dementia: an opinion poll among physicians.
AB  - OBJECTIVE: Dilemmas regarding selection of appropriate laboratory tests in older
      frail nursing home patients with advanced dementia are commonly encountered by
      physicians. Our objective was to study physician opinions about evaluating the
      appropriateness of laboratory testing in older hospitalized patients in nursing
      homes based on a real case. SETTING: A 750-bed university teaching hospital in
      the Bronx that regularly receives acutely ill older residents from long-term care
      facilities, with medical care provided by residents, fellows, and teaching
      faculty. DESIGN: An opinion poll was conducted among 53 physicians. Information
      was provided on the history, physical examination, and laboratory findings of a
      92-year-old woman with advanced Alzheimer's dementia admitted for
      gastrointestinal bleeding to the acute care Geriatrics unit. A questionnaire
      sought opinions on selection of laboratory tests (emphasizing Troponin I) and
      management in this patient. Chi-square analysis was performed to analyze the data
      RESULTS: The majority of polled physicians (37/53, P = 0.01) felt that ordering
      Troponin I in the setting described hindered patient care and stated they would
      not have ordered the test. The opinion on overall management was divided (P =
      0.861). CONCLUSION: Dilemmas regarding choosing appropriate laboratory tests,
      including their implications for care, are found frequently in the setting of
      frail, demented elderly from nursing homes hospitalized for acute care. We
      suggest that the choice of tests in these subjects with advanced dementia be
      individualized based on due consideration for life expectancy, quality of life,
      and surrogate opinion.

PMID- 12812614
TI  - Epididymo-orchitis: a differential diagnosis for hip pain in patients with
      dementia.
AB  - Epididymo-orchitis in the elderly is usually associated with urinary tract
      infections, prostatitis, and urethral manipulations. It usually presents as acute
      scrotal pain, and specific complaints direct further exam and work up. As persons
      with dementia are unable to give a history or localize pain, it can be
      overlooked. It mimicked as hip fracture in the case presented here.

PMID- 12812615
TI  - Ethics issues: using basic management techniques to improve end-of-life care:
      part III.

PMID- 12812616
TI  - Quality improvement case study: issues involving hidden video cameras in nursing
      home residents' rooms.

PMID- 12812617
TI  - The Shmoozers of Grancell Village.

PMID- 12812618
TI  - A comparison between lecture and videotape inservice for certified nursing
      assistants in skilled nursing facilities.
AB  - OBJECTIVE: Certified Nursing Assistants (CNA) provide most of the direct patient
      care in skilled nursing facilities (SNF). CNAs undergo mandatory inservice
      education regarding a variety of clinical conditions, but high CNA turnover and
      diverse cultural and educational backgrounds are persistent obstacles to overall
      staff education. A standardized, easily administered, highly reproducible
      training intervention would be valuable. We compared the efficacy of videotape
      versus standard lecture for inservice education relating to topics of dementia
      care, restraint use, and falls. DESIGN: A prospective randomized study. SETTING:
      Certified Nursing Assistants were recruited from three SNFs in San Diego County
      California between November 1997 and August 1998. PARTICIPANTS: The 82 CNAs who
      participated in the study were all CNA certified in California, employees of the
      study SNFs, and provided direct clinical care to SNF residents. All participants
      received regular inservice training. INTERVENTIONS: (1) Standard inservice
      lecture, (2) Videotape of inservice lecture material supplemented with brief
      clinical video vignettes. MAIN OUTCOME MEASURES: Scores on a 72-item multiple
      choice/true-false examination. MAIN RESULTS: Both lecture and video inservice
      education were effective in this CNA population. Test scores were significantly
      higher for both inservice groups compared with the control group (P < 0.001).
      There was no statistically significant difference between test scores for the two
      intervention groups (control = 63.1 +/- 8.2%, lecture = 78.2 +/- 8.9%, video =
      77.9 +/- 11.2%). Knowledge retention was similar between the two intervention
      groups at 4 months. Lecture subjects who scored highest were more likely to have
      family members with dementia (P = 0.037), and video subjects who scored highest
      were younger (P = 0.007). CNA video subjects who scored highest on the
      examination were more likely to have English as their primary language compared
      with the highest scoring CNA lecture subjects (P = 0.012). CONCLUSIONS: Compared
      with control group scores, videotape and lecture inservice interventions were
      equally effective at increasing and maintaining test scores. The ease of frequent
      video intervention and the identification of learner characteristics most suited
      to the video format make audiovisual education a potentially powerful medium for
      CNA training. These data have important implications for future educational
      interventions in the SNF.

PMID- 12812619
TI  - Drug consumption in a group of elderly residents of a nursing home: relationship
      to cognitive impairment and disability.
AB  - OBJECTIVES: The incidence of drug interactions and adverse reactions increases
      exponentially with increases in the number of medications consumed. The objective
      of this study was to investigate drug consumption, in particular nonsteroidal
      anti-inflammatory drugs (NSAIDs), and to assess the relationship between drug
      consumption and cognitive function and disability in a group of older people
      residing in a nursing home. PARTICIPANTS AND SETTING: Two-hundred residents (108
      women, 92 men) of a nursing home in Ankara, Turkey, mean age 77.2 +/- 8.7 years
      (range, 60-98), were included in the study. Data were obtained about
      sociodemographic variables and drug consumption, and the Mini-Mental State
      Examination (MMSE) and Functional Independence Measure (FIM) were used to assess
      the cognitive and functional status. RESULTS: The majority (94.4% of men and
      80.4% of women) were prescribed at least one drug, with a mean of 3.59
      prescriptions prescribed to women 2.39 to men. The mean number of self-prescribed
      drugs used by the elderly was higher than found in previous studies. Although
      there was not a statistically significant difference in regard to socioeconomic
      status and self-prescribed drug usage, we found a significant positive
      correlation between nonprescribed drug use and the scores of FIM and MMSE (P <
      0.05). The drugs self-prescribed most commonly were NSAIDs, with a rate of 72.5%.
      CONCLUSION: This study found high drug consumption correlated with poor cognitive
      and functional status in elderly residents of a nursing home.

PMID- 12812620
TI  - Predictors of hospital length of stay and nursing home placement in an elderly
      medical population.
AB  - OBJECTIVE: To identify predictors of adverse outcomes (nursing home placement and
      hospital length of stay) in a cohort of older hospitalized patients. DESIGN:
      Prospective cohort study. SETTING: A suburban medical center in the New York City
      metropolitan area. PARTICIPANTS: Patients aged 65 years and older admitted from
      the emergency department to medical services who could be seen within 24 hours.
      Patients with terminal illness, planned stays < 2 days, and admission to other
      than medicine were excluded. MEASUREMENTS: Sociodemographic data, mobility,
      Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL),
      mental status, length of stay (LOS), discharge diagnosis, and disposition
      (nursing home vs. other). RESULTS: Of 681 patients screened, 322 were eligible
      and assessed at admission,206 were reassessed at discharge. Using multiple
      regression, greater dependency in IADL, more household help, and impaired mental
      status at admission predicted hospital LOS significantly (P = 0.0001). Compared
      with those discharged home, the nursing home (NH) group had lower scores on mean
      mobility and mean ADLs and IADLs and was more likely to exhibit a decline in at
      least one ADL. Stepwise discriminant analysis was performed using admission,
      discharge, and combined variables. In our final model of the predictors of
      discharge disposition, the use of admission functional variables, age, and sex
      correctly classified 100% of the NH group and 91% of the other group, with IADL,
      ADL, and mobility defining the function that discriminated the groups.
      CONCLUSIONS: Our data indicate the value of cognitive and physical function at
      admission as predictors of adverse outcomes and support early assessment of the
      elderly for discharge planning for long-term care.

PMID- 12812621
TI  - Treatment of psychosis in Parkinson's disease.
AB  - Psychotic symptoms, including hallucinations, delusions, delirium,sleep-wake
      disturbances, are a common problem in Parkinson's disease and often lead to a
      significant decline in the patient's overall function. Treatment of these
      symptoms is a dilemma in patients with parkinsonism because traditional
      antipsychotics that are usually effective in older people will often worsen motor
      symptoms and counteract the effect of antiparkinsonian medications. Several new
      atypical antipsychotics and other drugs have now been tested in clinical trials
      and are much more effective in the alleviation of psychotic symptoms without
      worsening Parkinson symptoms. We have performed an extensive literature review of
      this topic and present detailed information on medications currently available
      for the treatment of psychosis in Parkinson's disease as well as some promising
      drugs that may be available in the future.

PMID- 12812622
TI  - Collaborative partnership for optimizing heart failure outcomes in the long-term
      care environment: a clinical experience.
AB  - RATIONALE: Heart failure (HF) is a devastating cardiovascular syndrome affecting
      more than 4.6 million Americans and resulting in a substantial economic burden.
      It is the number one cause of hospitalization in the older population. Because
      there is no cure for this costly disease, goals of therapy include; slowing
      progression, increasing patient survival, minimizing symptoms, improving patient
      functional capacity, and decreasing ER visits, hospital admissions, and
      readmissions. Studies have shown ACE inhibitors (ACEIs) to be extremely
      beneficial in reaching these goals. However, data nationwide indicate that less
      than half of HF patients are prescribed an ACEI. Therefore, a national long-term
      care pharmaceutical provider has committed to the development of a HF disease
      management program, which has been implemented through a collaborative
      partnership between medicine, nursing, and pharmacy. This report describes the
      experience and results of implementing this program in a large group of nursing
      homes. METHODS: With help from an independent health outcomes consulting firm and
      an expert panel, a multifaceted program was developed. The AMDA heart failure
      guidelines were used as a foundation to design program interventions, which
      included educational programs for the long-term care facility staff,
      implementation of a HF treatment algorithm, and an outcomes measurement program.
      The primary goals of this program were to increase awareness of HF and treatment
      options available and to decrease morbidity and mortality associated with HF
      through the optimization of pharmacologic management in a long-term care setting.
      OUTCOMES: A retrospective evaluation was conducted to assess changes in ACEI
      utilization, ACEI targeted dosing and HF-related hospitalizations 1 year after
      program implementation. A total of 510 patients followed by 23 consultants,
      representing 152 facilities met the inclusion criteria for the analysis. Data
      indicated an increase of 36% in newly enrolled HF patients utilizing ACEI after 1
      year. A decreasing trend in HF hospitalizations was also noted from the first
      quarter, (2.2/100 patients) to the fourth (1.0/100 patients). The results of the
      Heart Failure-Health Outcomes Management Program (HF-HOMP) program demonstrate
      the opportunity existing for long-term care providers to improve patient health
      while minimizing expenditures. It also provides additional evidence that such
      programs should be implemented more broadly within this population.

PMID- 12812623
TI  - Is stress testing a Hobson's choice in some geriatric patients?

PMID- 12812624
TI  - Wound care in the 21st century: lessons from ancient Egypt.
AB  - Wound care is becoming increasingly important to geriatricians and long-term care
      providers. Although pressure ulcers have recently taken the spotlight, wound care
      actually involves many other types of lesions found commonly in the nursing home
      environment. Physicians of ancient Egypt were experts in the art and science of
      healing wounds, as revealed by examination of the Smith Papyrus, one of the
      oldest medical texts in existence. Today, wound healing is no longer emphasized
      in medical training and practice. However, long-term care physicians and medical
      directors are in a perfect position to elevate wound care to its formerly
      preeminent position in medicine. To reach this goal, an agenda needs to be set
      for physician education on the techniques and tools of wound healing, including
      prevention, interdisciplinary collaboration, documentation, and correct choice of
      products.

PMID- 12812625
TI  - Ethics issues: using basic management techniques to improve end-of-life care:
      part II.

PMID- 12812626
TI  - Cigarette smoking and fire safety in the nursing home: case study with
      recommendations for smoking policy.

PMID- 12812627
TI  - [The influence of continuous renal replacement therapy on the plasma levels of
      endotoxin and cytokines in severely burned patients with sepsis].
AB  - OBJECTIVE: To investigate the influence of continuous renal replacement therapy
      (CRRT) on the plasma levels of endotoxin and cytokines in severely burned
      patients with sepsis. METHODS: Ten burn patients who received CRRT and another 10
      without CRRT were investigated in terms of the changes in their plasma
      concentrations of endotoxin and some cytokines (TNFalpha, IL-1beta, IL-6, IL-8).
      RESULTS: The plasma concentrations of endotoxin and all the cytokines (TNFalpha,
      IL-1beta, IL-6, IL-8) after CRRT treatment were significantly lower than those
      before the treatment (P < 0.01), and the plasma levels of the above factors at
      all the time points after CRRT treatment than those in patients were evidently
      lower by routine treatment (P < 0.05 - 0.01). CONCLUSION: CRRT treatment could
      effectively lower the plasma levels of endotoxin and some cytokines (TNFalpha, IL
      1beta, IL-6, IL-8).

PMID- 12812628
TI  - [Clinical significance of the predominant bacterial strains on burn wound during
      early postburn stage].
AB  - OBJECTIVE: To investigate the clinical significance of the predominant bacterial
      colonization on burn wound in our department during recent years, so as to help
      select optimal antibiotics in burn patients with severe infections. METHODS: This
      bacterial investigation was carried out in 215 cases of severely burned patients.
      The bacterial culture and the drug susceptibility test were carried out. RESULTS:
      (1) One hundred and twenty-two strains of bacteria were cultured, in which 28
      strains (23%) were Staphylococcus with negative coagulase, 27 (22%) S. aureus, 17
      (14%) Pseudomonas aeruginosa, 11 (9%) Escherichia coli, 10 (8%) Enterobacter, 9
      (7%), enterococci, 3 (2.5%) fungi, and 17 (14.5) other bacteria. (2) The
      resistance of S. aureus to ampicillin, oxacillin and amoxicillin/clavulanic acid
      was 81%, 38% and 31%, respectively. 11% and 16% of Pseudomonas aeruginosa
      resistant to Imipenem and Ceftazidime, respectively. (3) The sensitivity of G +
      cocci to vancomycin and norvancomycin, Chloramphenicol, Teicoplanin,
      Trimethoprim/Sulfamethoxaz, Rifampin was 100%, 100%, 100%, 94% and 88%
      respectively, and the Gram-negative bacilli to Meropenem, Imipenem, Amikacin,
      Cefepime, Cefoperazone/Sulbactam, Ceftazidime were 91%, 90%, 81%, 78%, 71% and
      70%, respectively. Furthermore, the sensitivity of Pseudomonas aeruginosa to
      Cefoperazone/Sulbactam, Ceftazidime, Tobramycin, Meropenem, Amikacin,
      Ciprofloxacin, Amikacin, Cefepime were between 82% and 91%. MRSA was very
      sensitive to both vancomycin and norvancomycin. CONCLUSION: The results suggested
      that Staphylococcus with negative coagulase and S. aureus were the predominant
      bacteria and Pseudomonas aeruginosa ranked second. The resistance of these
      bacteria to antibiotics was on the increase. Moreover, colonization of
      enterococcus and fungi on burn wound increased recently, which were scarce
      before. This implied the importance of rational and correct use of antibiotics
      during early postburn stage.

PMID- 12812629
TI  - [Clinical evaluation of the postburn retention and the metabolism of Imipenem in
      the third space].
AB  - OBJECTIVE: To explore the half life and retention of Imipenem in the third space.
      METHODS: Eight severely burned patients and eight healthy volunteers were
      enrolled as the burn group (B) and normal control group (C), respectively. HPLC
      (high performance liquid chromatography) was employed to determine the contents
      of Imipenem in the plasma, subeschar tissue fluid (STF) and the changes in its
      pharmacokinetics. Furthermore, the Imipenem content in the third space was
      calculated according to the systemic edema degree. RESULTS: The half life of
      Imipenem in STF (2.53 h) was longer than that in plasma (1.73 h), P < 0.05). The
      Imipenem content in STF increased gradually along with the lapse of time after
      repeated intravenous infusion of Imipenem, and at the same the total content of
      imipenem was increased significantly in the third space. CONCLUSION: There was
      antibiotic retention in the third space after severe burn injury, and a prolonged
      action of the drug could be expected when the drug re-entered the blood stream.

PMID- 12812630
TI  - [An experimental study on the role of PGE2 and cAMP on the postburn change of the
      granulopoiesis in bone marrow in burned mice with endotoxemia].
AB  - OBJECTIVE: To investigate the role of PGE(2) and cAMP in the postburn change in
      granulopoiesis in bone marrow in burned mice with endotoxemia. METHODS: One
      hundred and seventy eight mice were randomly divided into burn with LPS
      administration, simple burn, simple LPS administration and control (injection of
      normal saline) groups. The COX-2 expression and the contents of PGE(2) and cAMP
      in myeloid cells in injured mice in all groups were determined by RIA
      (radioimmuno-assay) within 1 postburn week and immunohistochemistry methods. At
      the same time the change in granulopoiesis was dynamically observed. RESULTS: The
      granulopoiesis was enhanced slightly at the early stage of burn and with
      endotoxin challenge, followed by suppression. The COX-2 expression in myeloid
      cells the contents of PGE(2) on supernatant of marrow cells and intracellular
      cAMP in the myeloid cells was increased at 12 postburn hour (PBH) up to 5
      postburn day (PBD). Furthermore, the change in the cAMP was evidently and
      positively correlated with that of PGE(2) (r = 0.978, P < 0.01), but was
      negatively correlated with that of CFU-GM (r = -0.971, P < 0.01) CONCLUSION:
      PGE(2) might play pivotal roles in the postburn granulopoiesis suppression in
      bone marrow during endotoxemia. This effect might be accomplished by its ligating
      to its special receptor and to activate adenylate cyclase so as to increase the
      intracellular content of cAMP in bone marrows.

PMID- 12812631
TI  - [The influence of the LPS from Bacteroides fragilis on the secretion of IL-2 and
      IL-4 from the peripheral blood mononuclear cells of normal volunteers].
AB  - OBJECTIVE: To investigate the influence of the LPS of Bacteroides fragilis on the
      secretion of IL-2 and IL-4 from the peripheral blood mononuclear cells of normal
      individuals, so as to elucidate the mechanism of the infection by Bacteroides
      fragilis. METHODS: LPS was obtained from both the strains isolated from patients
      and from standard NCTC9343. Peripheral blood mononuclear cells (PBMCs) were
      treated with different concentrations of LPS thus obtained. The supernatants from
      the cell culture of the PBMCs were harvested at 24 PBHs and were subjected to the
      determination of the IL-2 and IL-4 contents by ELISA method. RESULTS The IL-2
      secretion from the PBMCs of normal volunteers was obviously inhibited by the LPS
      from Bacteroides fragilis (P < 0.01), and the inhibitory effect was dose
      dependent. Nevertheless, the IL-4 secretion from the PBMCs of normal volunteers
      was significantly stimulated by the LPS from Bacteroides Fragilis (P < 0.05), and
      it was not concentration dependent. There was no difference between the effects
      of the LPSs from patients and standard strains (P < 0.05). CONCLUSION: The LPS
      from Bacteroides fragilis was inhibitory to the secretion of IL-2 from PBMCs and
      was stimulative to that of IL-4 from PBMCs of normal human persons.

PMID- 12812632
TI  - [The expression and analysis of its activity of anti-bacterial peptide gloverin
      in COS-7 cells].
AB  - OBJECTIVE: To investigate the expression and analysis of its activity of anti
      bacterial peptide gloverin in COS-7 cells. METHODS: The appearance frequency of
      all genetic codes in the cDNA sequence from the same species of protein Attacin A
      was analyzed, and its cDNA sequence was synthesized by PCR overlapping extension
      method in conjunction with the designation of the known protein sequence of
      gloverin. The genes were inserted into pCDSI, an eukaryotic vector, after being
      identified correctly. As a result, the vector pBZHG was constructed. Thereafter,
      the liposome FuGENE( trade mark ) 6 was employed as the vector, and the COS-7
      cells were transfected with liposome pBZHG and blank vector pCDSI. The normal
      cells were taken as the control. The supernatant was collected for the detection
      of its bactericidal activity after 72 PBHs. RESULTS: The gloverin cDNA sequence
      designed artificially was expressed in COS-7 cells. The supernatant of the cells
      transfected by pBZHG exhibited bactericidal activity to E. coli J5 when compared
      with that from normal cells and in cells transfected with blank vectors.
      CONCLUSION: The designed cDNA sequence of gloverin was proved to be genuine, and
      it provided the basis for future study of its antibiotic and anti-endotoxin
      activities.

PMID- 12812634
TI  - [The postburn changes in gastric mucosal blood flow and Na+-K+-ATPase activity
      and their effects on gastric transmucosal potential difference in severely
      scalded rats].
AB  - OBJECTIVE: To investigate the postburn changes in gastric mucosal blood flow
      (GMBF) and Na(+)-K(+)-ATPase activity and their effects on gastric transmucosal
      potential difference (GTPD) in severely scalded rats. METHODS: Rats were
      inflicted with hot water scald on the back. Laser Doppler blood flow meter,
      electric physiological recorder meter and biochemical method were employed in the
      study to determine the changes in GMBF, GTPD and gastric mucosal Na(+)-K(+)
      ATPase activity in the rats before injury and at 3, 6, 12, 24 and 48 PBHs. Normal
      rats served as controls, The above indices were also detected at the
      corresponding time points. All the data was collected and analyzed for their
      correlation. RESULTS: The GMBF and Na(+)-K(+)-ATPase activity was at 3 - 24 PBHs
      were evidently lower in the scalded rats than those in controls (P < 0.05 -
      0.01). GTPD was decreased significantly at 6 - 48 PBHs (P < 0.05 - 0.01). was
      above three indices reached the lowest values at 12 PBH. By correlation analysis
      the results indicated that the Na(+)-K(+)-ATPase activity The decreased in
      accordance with a decrease in GMBF (r = 0.527, P < 0.01). The GTPD decrease could
      both be induced by GMBF decrease and Na(+)-K(+)-ATPase activity decrease (r =
      0.453 and 0.527, respectively, P < 0.01). CONCLUSION: The decrease in GMBF and
      Na(+)-K(+)-ATPase activity occurred in severely scalded rats, both changes might
      be the major cause of postburn gastric mucosal barrier injury.

PMID- 12812633
TI  - [An experimental study on the prevention and treatment of postburn intestinal
      injury and bacterial translocation by Sijunzi decoction in scalded rats].
AB  - OBJECTIVE: To explore the effects of traditional Chinese herbal medicine Sijunzi
      decoction on amelioration of postburn intestinal injury in scalded rats. METHODS:
      One hundred and eighty Wistar rats were randomly divided into 3 groups, i.e.
      scald and treatment (T), scald control (S) and normal control (C) groups. The
      rats in T group were gavaged with the decoction consisting of tangshen, tuckahoe,
      large head atractylodes rhizome, glycyrrhizic and rhubarb in a dose of 2 ml twice
      daily, while the rats in C group were just gavaged with the same amount of
      distilled water. The rats were sacrificed according to the scheduled postburn
      observation timepoints. The contents of TNF, NO, MDA and ATPase activity in rat
      plasma and the intestinal mucosa and the S-IgA content in the intestinal mucus
      were determined respectively. The changes in histopathology of intestinal mucosa
      were observed. The samples from internal organ tissue and blood were obtained for
      bacterial culture. RESULTS: The contents of TNF, NO and MDA in the intestinal
      mucosa tissue and the rat plasma in scalded rats were lowered significantly by
      Sijunzi decoction. Furthermore, S-IgA secretion from intestinal mucous cells was
      maintained by Sijunzi decoction. T cell count was recovered and intestinal mucous
      barrier injury were lessened, and the bacterial positive rate in the internal
      organs was decreased. CONCLUSION: Traditional Chinese herbal medicine Sijunzi
      decoction might be helpful in alleviation of postburn intestinal injury and in
      the prevention of intestinal bacterial translocation.

PMID- 12812635
TI  - [An observation of the effects of recombinant human transforming growth factor
      beta3 on fibroblast].
AB  - OBJECTIVE: To investigate the role of recombinant human transforming growth
      factor beta3 (rhTGFbeta3) on fibroblast and its possible mechanism. METHODS:
      Normal skin fibroblast (NSFb) and hypertrophic scar fibroblast (HSFb) were
      cultured in vitro, and were processed by different concentrations of rhTGFbeta3.
      NSFb and HSFb in DMEM solution without rhTGFbeta3 were employed as control. The
      changes in the protein and mRNA expression of type I and III collagen in NSFb and
      HSFb were observed. RESULTS: (1) The expression of type I and III procollagen in
      NSFb was evidently different from that of HSFb (2) The synthesis of type I and
      III procollagen in all test groups was increased obviously after rhTGFbeta3
      process (P < 0.001) while the ratio of type I to III procollagen was decreased
      when compared with that in control group. (3) The effects of rhTGFbeta3 on the
      biological behavior exhibited an obvious dose- effects relationship. The contents
      of type I to III procollagen in HSFb were higher than those in NSFb when the dose
      of rhTGFbeta3 was same. CONCLUSION: rhTGFbeta3 could effectively promote the
      synthesis of type I and III procollagen, especially type III procollagen in
      fibroblasts. This might be beneficial to the accelerate of wound healing and to
      inhibit or prevent scar formation.

PMID- 12812636
TI  - [Study on the mechanism of the effects of recombinant rat tumor necrosis factor
      alpha on the degradation of rat skeletal muscle proteins].
AB  - OBJECTIVE: To investigate the mechanism and the effects of intravenously injected
      tumor necrosis factor alpha (TNFalpha) on skeletal muscle protein degradation in
      rats and its relationship with glucocorticoid. METHODS: Forty-five male Wistar
      rats were randomly divided into 3 groups as A (control), B (TNFalpha injection)
      and C (TNFalpha and glucocorticoid receptor antagonist injection) groups.
      TNFalpha in dose of 1x 10(6) units/kg was given to rats in B group intravenously.
      RU38486, a glucocorticoid receptor antagonist, was given by gavage in C group 2
      hours before intravenous injection of TNFalpha in the same dose as in B group.
      the rat temperature was monitored 12 hours after the administration of the drugs.
      At the same time, the rat extensor digitorum longus muscles (EDL) were isolated,
      weighed and cultured under aerobic condition, and than the degradation rates of
      total and the myofibrillar proteins were determined with HPLC (high performance
      liquid chromatography), and the expression changes in C2 subunit mRNA and
      ubiquitin mRNA were detected by Northern blot. RESULTS: Twelve hours after the
      injection, the temperature of the rats in B and C group was much higher than that
      in A group (P < 0.01), while the weight of the extensor digitorum longus muscle
      in B and C groups was evidently lower than that in A group (P < 0.01) whereas
      that in C was higher than that in B groups (P < 0.05). The degradation rates of
      total and the myofibrillar proteins in B group were increased by 43% and 112%,
      respectively, when compared with those in A group (P < 0.01), while the rates in
      C group was decreased by 16% and 28%, respectively, when compared with those in B
      group (P < 0.01). In addition, the expressions of ubiquitin mRNA (2.4 kb) and C2
      subunit mRNA in B group were increased 4.3 and 3.6 fold compared with those in A
      group, whereas those in C group were much lower than those in B group.
      CONCLUSION: Intravenous injection of recombinant TNFalpha in large dose might
      enhance the activity of rat skeletal muscle ubiquitin-proteasome system pathway,
      which led to an increase in the degradation rate of rat total protein, especially
      the myofibrillar protein. Glucocorticoid was one of the mediating factors of that
      effect.

PMID- 12812637
TI  - [Study on the typing of immunocytes after xenogeneic or allogeneic acellular
      dermal matrix grafting].
AB  - OBJECTIVE: To investigate the immunologic reaction difference between xenogeneic
      and allogeneic acellular dermal matrix (ADM) grafting. METHODS: Split thick skin
      samples harvested from healthy piglets and human volunteers who underwent losing
      weight operation were processed to be xeno-ADM and allo-ADM. The ADMs overlapped
      with ultrathin auto-skin were employed to immediately cover the wound after
      escharectomy in deep burn patients. The patients were correspondingly set to be
      Xeno (26 cases) and Allo (10 cases) groups. Another 8 cases with deep burn wounds
      were grafted with only split thick autoskin (TTS) after escharectomy as control
      group. The tissue samples from grafted area were observed by immunohistochemistry
      after the grafting. The typing of immune cells in peripheral blood and grafted
      tissue was determined. RESULTS: (1) The CD4(+), CD45RO(+) and CD4(+)/CD8(+) cell
      ratios in peripheral blood in Xeno group increased slightly after the skin
      grafting when comparing to those in control group (P > 0.05). (2) There existed
      lasting inflammatory and immunological reaction in the local site of grafts in
      Xeno group. In addition, more than 80% of the inflammatory cells could be found
      to be CD3(+)/CD4(+), CD45RO(+). But CD8(+), Vs8C(+) plasmocytes and CD57(+) NK
      cells were found less. Furthermore, eosinophil and CD68(+)/CD4(+) foreign body
      megalocyte reactions could also be identified, especially in Xeno-ADM before
      rejection (P < 0.05 - 0.001). There was only mild inflammatory and immunological
      reaction during early grafting stage (within 8 post-operational weeks) in Allo
      group. CONCLUSION: The specific immunologic reaction of human host to ADM might
      be participated by mononuclear cells and macrophages and presented mainly as
      cellular immune reaction induced by CD4(+) T lymphocytes. Furthermore, the
      foreign body megalocyte constructed by help T cell and macrophage might play
      important roles in the reaction.

PMID- 12812638
TI  - [An observation of the effects of Tiopronin on the oxygen free radicals in
      severely scalded rats receiving delayed fluid resuscitation].
AB  - OBJECTIVE: To observe the harmful effects of oxygen free radicals and the
      protective roles of Tiopronin in severely scalded rats after delayed fluid
      resuscitation. METHODS: Rats inflicted with 30% III degree scald on the back were
      employed as the model. They were divided into delayed resuscitation (D) and
      Tiopronin treatment (T) groups. The changes in superoxide dismutase (SOD) and
      malonyldialdehyde (MDA) in plasma and subeschar fluid were determined at 24 to 48
      postburn hours (PBHs) by means of electron spin resonance (ESR) technique and
      other routine methods. And the pathomorphological changes in the heart, liver,
      kidneys and small intestine, and changes in the blood biochemical indices were
      simultaneously determined. Normal rats were taken as control group (N). RESULTS:
      The plasma SOD level was was lower than that in N group, while the MDA content in
      plasma and subeschar fluid in D group was much higher than that in N group.
      Changes in all the blood biochemical and internal organ pathomorphology were more
      obvious in the D group. on the other hand, the rat plasma SOD level in T group
      increased obviously (P < 0.01) while the MDA contents was decreased in T group (P
      < 0.05) when compared with those rats of D group. In addition, the internal organ
      pathomorphology and blood biochemical indices were improved evidently in T group.
      CONCLUSION: Oxidative stress injury was evoked in severely scalded rats after
      delayed fluid resuscitation, and it could be protected to some extent by
      Tiopronin.

PMID- 12812639
TI  - [The significance and the expression of homeobox genes during human burn wound
      healing].
AB  - OBJECTIVE: To investigate the expression of several homeobox genes during the
      wound healing in fetal and adult skin and their roles in fetal scarless wound
      healing. METHODS: The expressions of PRX-2, HOXB13, HOX2.2 and HOX2.3 during
      wound healing in fetal and adult skin were determined with in situ hybridization.
      RESULTS: (1) PRX-2 positive expression could be identified in normal fetal and
      adult skin, especially in the fetus. But there was difference in location sites
      of the genes. The positive expression in normal fetal skin was mainly found in
      the peripheral cells at the hair shafts within dermal papilla layers and was also
      found in the epithelium. Nevertheless, weak positive expression of PRX-2 was
      found in the epithelial basal layer cells in normal adult skin but not in dermal
      tissue. There was strong positive expression of the PRX-2 in the tissue around
      the wound in fetus but not of that in adults except the epithelial basal layers.
      (2) Positive expression of HOXB13 could be identified in both normal fetal and
      adult skins. And the expression was concentrated mainly in hair follicle cells in
      the dermis and in the basal layer cells in the epithelium. Furthermore, the
      expression became weak after trauma, especially in fetal skin. (3) The positive
      expression of HOX2.2 and HOX2.3 in normal fetal skin was observed mainly in the
      whole layer of the epithelium and especially in the epithelial basal layers. Weak
      positive expression could be found in the dermis and strong expression found in
      the tissue near the wound. But there was no positive expression of the HOX genes
      in normal adult skin and wounds. CONCLUSION: The difference in the HOX expression
      in fetal and adult skin wound healing might be the key factor leading to
      different wound healing. Homeobox genes might be closely related with the
      developmental biology.

PMID- 12812641
TI  - [Sensitivity of distortion product otoacoustic emissions and auditory brain-stem
      response in neonatal hearing screening, a comparative study].
AB  - OBJECTIVE: To investigate the sensitivity of distortion product otoacoustic
      emissions (DPOAE) and auditory brain-stem response (ABR) in neonatal hearing
      screening. METHODS: DPOAE and ABR were conducted on 99 neonates (198 ears) at
      risk of hearing impairment as initial screening tests. One month later
      rescreening tests were conducted: DPOAE was conducted again on those ears failing
      this test during the initial screening test and ABR was conducted again on the
      ears failing this test during the initial screening test Those ears failing the
      DPOAE and ABR tests during the rescreening tests were examined with electric
      otoscope, diagnostic ABR, etc. to get confirmed diagnosis. RESULTS: 54 ears (27%)
      failed the DPOAE test during the initial screening and 14 out of the 54 ears
      (14/198, 7%) still failed the DPOAE test during the rescreening. 26 ears (12%)
      failed the ABR test during the initial screening and 9 out of the 16 ears (9/198,
      4.5%) still failed this test during the rescreening. Two babies were confirmed as
      with severe sensorineural hearing loss, one unilateral and one bilateral. The
      sensitivity was 97% for DPOAE and 99% for ABR. CONCLUSION: ABR is a little bit
      more sensitive then DPOAE in neonatal hearing screening. Two-stage testing
      procedure increases the sensitivity of neonatal hearing screening.

PMID- 12812640
TI  - [Hearing screening of 10,501 newborns].
AB  - OBJECTIVE: To investigate the results of hearing screening in newborns so as to
      explore the appropriate clinical strategy of hearing screening among newborns.
      METHODS: Transiently evoked otoacoustic emission (TEOAE) was used to examine the
      hearing of 10,501 newborns 2 - 4 days after birth. Those who failed the initial
      screening underwent secondary screening with TEOAE. Acoustic brain-stem response
      (ABR) and 40 Hz AERP were used to monitor the hearing of those who failed the
      secondary screening every 6 months since the age of 3 months to the age of 3
      years. RESULTS: The false-positive rate was 14.92% in the initial screening, and
      was 0.26% after the 2-stage screening. 62 infants were diagnosed with hearing
      loss with a prevalence of congenital hearing loss (in one ear or two ears) of
      5.90 per thousand and a prevalence of bilateral hearing loss of 2.76 per
      thousand. CONCLUSION: Hearing screening in the procedure with TEOAE, ABR and 40
      Hz AERP helps identify infants with hearing loss as early as possible so as to
      conduct appropriate intervention.

PMID- 12812642
TI  - [Neurophysiological characteristics of infants and young children with auditory
      neuropathy].
AB  - OBJECTIVE: To analyze the neurophysiological characteristics of infants and young
      children with auditory neuropathy (AN) and explore their clinical significance.
      METHODS: Audiological measurements (acoustic immittance, EOAEs, ABR, CM, MLR and
      ERP) and peripheral neurological tests were conducted and evaluated in 13 infants
      and young children with AN. 6 AN patients received CT scan and/or MRI
      examination. RESULTS: All patients had type "A" tympanogram and normal CM. Normal
      EOAEs were elicited in 12 patients. 8 cases had normal MLR recording and 6 cases
      had normal ERP (P(300) and MMN). Peripheral neurological tests and CT and/or MRI
      showed normal results. CONCLUSION: The diagnosis of AN in infants and young
      children should focus on analyzing their neurophysiological characteristics.
      Combined use of EOAEs, ABR and CM was recommended for hearing screening on
      newborns with high risk factors.

PMID- 12812643
TI  - [Hearing screening for high-risk newborns].
AB  - OBJECTIVE: To investigate the morbidity of congenital hearing impairment among
      high-risk newborns and the relevant pathogenic factors. METHODS: Initial
      screening of hearing by otoacoustic emission (OAE) was conducted among 208 high
      risk newborns, 130 males and 78 females after they were born and the second
      screening was conducted by OAE was conducted 42 days after those with positive
      results were examined by auditary brainstem response (ABR). RESULTS: All of the
      208 newborns received the initial screening with a screening rate of 100%, and
      130 newborns received the second screening with a screening rate of 62.5%. The
      positive rates in the initial screening and second screening were 34.61% and
      7.14% respectively. Six newborns were examined by ABR and 2 of them were
      diagnoses as with hearing impairment with a prevalence rate of 1.78%. The
      factors, such as sex, age, and Apgar score affected the initial screening
      results. CONCLUSION: The most proper time for initial hearing screening is around
      the 42nd day after birth. High-risk newborns should receive regular test even
      though they pass the initial screening. A special follow-up system should be
      constructed for the high-risk newborns.

PMID- 12812644
TI  - [Significance of vascular lesions in IgA nephropathy and their influencing
      factors, a study of 1,005 cases].
AB  - OBJECTIVE: To analyze the characteristics of vascular lesions and their
      influencing factors in IgA nephropathy (IgAN). METHODS: The clinical and
      pathologic materials of 1,005 IgAN patients were analyzed. RESULTS: Of the 1005
      IgAN patients 54.6% were with vascular lesions. The patients with vascular
      lesions were older, underwent renopuncture earlier, and had a longer duration of
      disease than those without vascular lesions (all P < 0.01). The patients with
      severe vascular lesions were older and underwent renopuncture at older age in
      comparison with those with mild vascular lesions (P < 0.05 and P < 0.01). The
      patients with moderate vascular lesions had a longer course than those with mild
      lesions (P < 0.01). The systolic pressure and diastolic pressure of patients with
      severe, moderate, and mild vascular lesions were higher than those in patients
      without vascular lesions (all P < 0.01). The systolic pressure and diastolic
      pressure were significantly higher in the patients with severe vascular lesions
      than in those with mild vascular lesions (P < 0.01 and P < 0.05). The serum
      triglyceride level was significantly higher in the patients with severe,
      moderate, and mild vascular lesions than in those without vascular lesions (all P
      < 0.01). The serum triglyceride level was significantly higher in the patients
      with severe vascular lesions than in those with mild vascular lesions (P < 0.01).
      The levels of urine protein of all patients with vascular lesions were
      significantly higher than that of those without vascular lesions (all P < 0.01).
      The urine protein level was significantly higher in the patients with severe
      vascular lesions than in those with moderate and mild vascular lesions (both P <
      0.01). The serum creatinine was higher in all patients with vascular lesions than
      in those without vascular lesions (all P < 0.01) and was significantly higher in
      the patients with severe and moderate vascular lesions than in those with mild
      vascular lesions (P < 0.05 and P < 0.01). The blood albumin level was
      significantly lower in all patients with vascular lesions than that in those
      without vascular lesions (all P < 0.01). The higher the pathological grade of the
      nephropathy, the more severe the vascular lesion (P < 0.01). The C3 deposition
      along the interstitial vascular wall was more severe in those with vascular
      lesions than in those without vascular lesions (P < 0.01). Multivariate logistic
      regression analysis showed that the significant influencing factors on vascular
      lesions included hypertension, high serum uric acid, global glomerular sclerosis
      (>or= 50%), interstitial inflammation (>or= 50%) and pathological grade III-V.
      CONCLUSION: In patients with IgAN, vascular lesion parallels the blood pressure,
      serum triglyceride, urine protein, serum creatinine, etc. It reflects the disease
      degree and can be used as an important histological prognostic indicator.

PMID- 12812645
TI  - [Pit pattern and endoscopic mucosal resection in diagnosis and treatment of
      colorectal tumors].
AB  - OBJECTIVE: To explore the effective methods to diagnose and treat colorectal
      cancer in its early stage. METHODS: 1 205 patients were examined by colonoscopy
      and mucosa staining with indigocarmine. The pit patterns were observed with
      magnifying endoscope and stereomicroscope according to the Kudo classification.
      The pathological diagnoses of the lesions were compared with their pit patterns.
      Electrocoagulation resection was performed on the prominent lesions and
      endoscopic mucosal resection (EMR) or endoscopic partial mucosal resection (EPMR)
      was performed on the flat lesions. RESULTS: In the 282 patients 478 prominent and
      flat lesions were found. There were 16 cases of laterally spreading tumor (LST),
      including I case of pit pattern II, 6 of pit pattern IIIL, 8 of pit pattern IV,
      and 1 of pit pattern Va, with 2 cases of intramembrane cancer and 1 case of IIa +
      IIc lesions invading the superficial myometrium among them. EMR and EPMR were
      performed on 14 LST lesions, 22 IIa lesions, and 14 IIb lesions. CONCLUSION: The
      examination of pit pattern is very important in early diagnosis of colorectal
      cancer and differentiation tumorous from non-tumorous lesions. V type pit pattern
      is an indicator of colorectal cancer. EMR and EPMR are safe and effective for
      flat lesions.

PMID- 12812646
TI  - [Preimplantation genetic diagnosis for beta-thalassemia].
AB  - OBJECTIVE: To investigate the effect of in vitro fertilization and embryo
      transfer (IVF-ET) and preimplantation genetic diagnosis (PGD) for the couples at
      risk of having children with beta-thalassemia. METHODS: Four couples carrying
      different thalassemia mutations received standard IVF treatment. Embryo biopsy
      was conducted. Single blastomeres were genotyped by a protocol involving primer
      extension preamplification, nested polymerase chain reaction and reverse dot-blot
      analysis. Only the unaffected embryos were transferred to the uterus. RESULTS: A
      total of 97 oocytes were retrieved from the four female carriers. Among them, 83%
      showed two pronuclei. Embryo biopsy was performed on 47 of these embryos. The
      amplification efficiency was 84.8%. The average ADO rate was 14.9%. Ten
      unaffected embryos were transferred. A twin pregnancy with one blighted ovum was
      confirmed at 7 weeks' gestation by ultrasonography and one normal baby and one
      carrier of thalassemia mutation were born finally. CONCLUSION: This unaffected
      pregnancy resulting from PGD for beta-thalassemia demonstrates that PGD technique
      can be a powerful diagnostic tool for couples carrying beta-thalassemia mutations
      who desire a healthy child and wish to avoid abortion of an affected fetus.

PMID- 12812647
TI  - [Surveillance of incidence of cerebral hemorrhage in community populations in
      Changsha].
AB  - OBJECTIVE: To observe the incidence of cerebral apoplexy among the community
      populations in Changsha, Hunan Province. METHODS: Surveillance of the incidence
      of cerebral apoplexy and analysis of its subtypes were conducted among 10,000
      urban residents in Changsha selected by random cluster sampling from 1986 to
      1990. The number of people under surveillance was amplified to 50,000 in 1991 and
      the studies lasted to December 2000. RESULTS: Among the Chamgsha populations, the
      annual average incidence of cerebral hemorrhage was 171.7 per 100,000 during the
      period 1986 - 1990. The annual average incidence of cerebral apoplexy was
      238.9/100,000 with an adjusted rate of 200.2/100,000, and the annual average
      incidence of cerebral hemorrhage, accounting for 53.8% of cerebral apoplexy, was
      128.5/100,000 with an adjusted rate of 100.3/100,000). CONCLUSION: The annual
      average incidence of cerebral hemorrhage in community populations is 128.5 per
      100,000 during the period of fifteen years, 1986 - 2000, in Changsha, one of the
      areas with high incidence of cerebral hemorrhage.

PMID- 12812648
TI  - [Minimal invasive treatment of early esophageal cancer and its precancerous
      lesion: endoscopic mucosal resection using transparent cap-fitted endoscope].
AB  - OBJECTIVE: To explore the effect of endoscopic esophageal mucosal resection using
      transparent cap-fitted endoscope to treat early esophageal cancer and severe
      hyperplasia, precancerous lesion of esophageal cancer. METHODS: Endoscopic
      esophageal mucosal resection were performed with transparent-cap technique on 29
      cases of early esophageal cancer and 42 cases of severe hyperplasia, and the
      residual lesions were treated by Argon plasma coagulation (APC). All patients
      were followed up by endoscopic examination one month, 4 months, and 12 months
      after the therapy. RESULTS: (1) Local esophageal mucosa with the size of 21.8 mm
      +/- 1.02 mm x 18.2 mm +/- 1.02 mm on average was resected from 71 cases, with 88
      lesions, using transparent cap-fitted endoscope. 1:1,000 saline-epinephrine at an
      average dose of 18 ml was injected submucosally for each lesion. (2) After the
      mucosectomy 5 cases had bleeding which was controlled successfully by
      compression, local injection of saline-epinephrine, and APC. None case suffered
      from perforation. Stenosis was found in 4 cases after mucosal resection, in three
      of which the extent of resected mucosa exceeded 3/4 of the esophageal
      circumference. Water-balloon dilator was used once a month for 3 - 4 times since
      one month after mucosal resection. All cases were cured. (3) The lesions of 58
      cases (81.2%) were completely resected, and the remaining cases had residual
      lesions that were treated by APC. Three cases of early cancer and 2 cases of
      severe atypical hyperplasia were discovered endoscopically 4 months after
      resection and were cured by APC. (4) All cases survived without any discomfort
      after a follow-up of 4.6 months on average. CONCLUSION: Safe, simple, minimally
      invasive and effective on early esophageal cancer and precancerous lesion,
      endoscopic esophageal mucosal resection (EEMR) is promising clinically.

PMID- 12812649
TI  - [Genotype-phenotype correlation of patients with wilson disease in Chinese
      population].
AB  - OBJECTIVE: To investigate the correlation between genotype and phenotype of
      patients with Wilson disease (WD) in the Chinese population. METHODS: Using
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and
      subsequent direct sequencing to identify the mutations of ATP7B. Statistical
      analysis was performed using t test or chi(2) test. RESULTS: The common mutation
      Arg778Leu was homozygous in 18 patients. It was also found to be heterozygous in
      29 patients. 11 of 29 patients who carried another missense mutation in the other
      chromosome were regarded as Arg778Leu compound heterozygotes. We observed that
      the average age at onset in Arg778Leu homozygotes was significantly younger than
      that in Arg778Leu compound heterozygotes (P < 0.05). The average ceruloplasmin
      level of Arg778Leu homozygotes was significantly lower than that of Arg778Leu
      compound heterozygotes (P < 0.001). CONCLUSION: The result shows that Arg778Leu
      homozygotes are associated with the early onset of WD with hepatic presentation.
      The Arg778Leu mutation is not a mild mutation. It has severe effects on the
      function of ATP7B.

PMID- 12812650
TI  - [Two novel factor V gene mutations associated with congenital coagulation factor
      V deficiency, study of one pedigree].
AB  - OBJECTIVE: To discover the gene mutations of a pedigree with inherited factor V
      (FV) deficiency. METHODS: The activated partial thromboplastin time (APTT),
      prothrombin time (PT), FV activity (FV:C) and FV antigen test were adopted for
      phenotype diagnosis. The genomic DNA was extracted from the peripheral blood of
      the 16-year-old propositus, female. All the 25 exons and their flanks in the FV
      gene of the propositus were amplified by polymerase chain reaction (PCR). The PCR
      products were screened by direct sequencing and the mutations were further
      confirmed by restricted enzyme digestion. Six persons in the pedigree
      (grandfather, grandmother, father, mother, uncle, and aunt) were examined too.
      108 healthy blood donors were used as controls. RESULTS: The APTT, PT, FV:C, and
      FV:Ag of the propositus were 126.6s, 42.8s, 0.3% and 1.3% respectively. The Fbg
      and FII, FVII, FVIII, FIX, FX activities were in normal range. FV:C of the
      members of the pedigree was 36% - 70%, and the FV:Ag of the pedigree members was
      26.4% - 45.3% that of the mixture of 30 normal plasma samples. Taking the
      GeneBank Z99572 sequence as the reference, totally five variations in the FV gene
      were found in the propositus. The mutations, A1348G and 4887 approximately 8delG,
      were traced to her father and her mother respectively. No 1348G-->T mutation was
      found in the 108 controls. CONCLUSION: The FV deficiency of the propositus is
      caused by missense mutation of G1348T and frameshift mutation of 4887
      approximately 8delG, which haven't been identified previously.

PMID- 12812651
TI  - [Deletion of p15 and p16 genes and overexpression of STK15 gene in human
      laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the association of p15 and p16 genes deletion, and
      STK15 gene overexpression with laryngeal squamous cell carcinoma (LSCC). METHODS:
      The cancer tissue and surrounding normal tissue were taken during operation from
      50 cases of LSCC who had undergone neither chemotherapy nor radiotherapy
      preoperatively. DNA was extracted and PCR was used to test the homozygous
      deletion of p15 exon 2 (p15E2) and p16 exon 2 (p16E2). RNA was extracted, cDNA
      was synthesized by reverse transcription, and the expression of STK15 gene was
      tested by PCR with beta-actin as inner control. At the same time the expression
      of STK15 in human LSCC Hep-2 cell line was tested. The ratio of ADV (average
      density value) of STK15 gene to the ADV of beta-actin gene was calculated.
      RESULTS: The rate of p15E2 deletion was 12% (6/50) and that of p16E2 was 14%
      (7/50). The p15E2 and p16E2 codeletion rate was 6% (3/50). In 34 of the 50 cases
      (68%) the expression of STK15 gene in tumor tissue was higher than that of the
      paired surrounding normal tissue with a significant difference. The ratio of ADV
      of STK15 gene to ADV of beta-actin gene was 1.03 +/- 0.30 in the cancer tissue,
      and 0.89 +/- 0.22 in the paired normal tissue with a significant difference (t =
      4.333, P < 0.01). The expression of STK15 gene was higher than that of beta-actin
      in Hep-2 cell line. CONCLUSION: The homozygous deletion of p15E2 and p16E2 and
      overexpression of STK15 gene may play a role in the oncogenesis and malignant
      progression of laryngeal squamous cell carcinoma.

PMID- 12812652
TI  - [p33(ING1) gene expression and mutation in stomach cancer tissues and
      precarcinomatous tissues].
AB  - OBJECTIVE: To analyze the relationship of p33(ING1) gene expression and p33(ING1)
      exon-2 mutation to the pathogenesis, development and consequence of stomach
      cancer. METHODS: Envision immunohistochemical method was utilized to detect the
      p33(ING1) expression in 103 specimens of stomach cancer, 36 specimens of stomach
      mucosal atypical hyperplasia, and 32 specimens of normal stomach mucosa. PCR-SSCP
      was utilized to detect p33(ING1) exon-2 mutation in stomach cancer tissues.
      RESULTS: The p33(ING1) expression rate in stomach cancer was 54.4% (56/103),
      significantly lower than that in precarcinomatous tissues (94.4%, 34/36, P <
      0.01) and that in normal tissues (100%, 32/32, P < 0.01). The p33(ING1)
      expression in stomach cancer was related to tumor growth, distant metastasis and
      tumor differentiation (all P < 0.05). p33(ING1) gene exon-2 mutation was detected
      in 3 cases of stomach cancer tissues (12%, 3/25), and not in other tissues by PCR
      SSCP method. CONCLUSION: p33(ING1) low expression, and gene p33(ING1) exon-2
      mutation may play an important role in the pathogenesis, development and
      consequence of stomach cancer.

PMID- 12812653
TI  - [Changes of STAT3 in cell replicative senescence and effects of angiotensin II on
      STAT3].
AB  - OBJECTIVE: To investigate the changes of STAT3 in cell replicative senescence and
      the effects of angiotensin II (AngII) on STAT3. METHODS: Normal human fetal lung
      diploid fibroblast cell line WI-38 was cultured and the senescent cell was
      defined with beta-gal staining. Electrophoretic mobility shift assay and Western
      blotting assay were used to detect the activation of STAT3 during cell
      replicative senescence and examine the process of STAT3 activation with AngII.
      RESULTS: The synthesis of STAT3 protein during the course of cell replicative
      senescent increased, the nuclear translocation of phosphorylated STAT3 decreased,
      and the activities of STAT3 binding DNA reduced. CONCLUSION: AngII induces the
      activation of STAT3 in both mature and senescence cell by AT(1) receptor,
      however, the reaction of senescent cell to AngII is weaker. The site of block may
      be in the nuclear translocation. AngII induces the activity of STAT3 in
      replicative senescence WI-38.

PMID- 12812654
TI  - [The overexpression of prion protein in drug resistant gastric cancer cell line
      SGC7901/ADR and its significance].
AB  - OBJECTIVE: To investigate the overexpression of prion protein (PrP) in drug
      resistant gastric cancer cell line SGC7901/ADR and its role in multidrug
      resistance in gastric cancer. METHODS: (1) The expression of PrP in SGC7901/ADR,
      SGC790/VCR and their parental cell line SGC7901 was detected with Northern and
      Western blot at the mRNA and protein level. (2) Eukaryotic sense and antisense
      expression vector were constructed based on DNA recombination technology and (3)
      introduced into SGC7901 and SGC7901/ADR cell lines through electroporation. (4)
      The accumulation and retention of ADR in transiently transfected cells were
      detected by flow cytometry. RESULTS: (1) Northern and western blot suggested
      significantly higher expression of PrP in SGC7901/ADR and SGC7901/VCR than that
      in SGC7901. (2) 48 hours after the vectors transfection, the average fluorescence
      intensity of Adr in transfected cells were detected. The accumulation intensity
      were 8.9 +/- 0.7 in BS, 6.6 +/- 0.3 in PS and 7.5 +/- 0.6 in PA. The retention
      intensity were 9.3 +/- 0.6 in SGC7901, 5.9 +/- 0.5 in PS and 7.1 +/- 0.5 in PA.
      There were significant difference between PS and BS with P < 0.01, as well as RA
      and BA with P < 0.01. These data suggested that PrP gene could affect the drug
      accumulation in gastric cancer cells after its transfected into cells.
      CONCLUSION: PrP was highly expressed in gastric cancer cell lines SGC7901/ADR and
      SGC7901/VCR. Overexpression of PrP had certain effect on drug accumulation in
      gastric cancer cells.

PMID- 12812655
TI  - [Expression of human-mouse chimeric antibody ch-BD1 and its affinity to human
      bladder cancer in vitro and in vivo].
AB  - OBJECTIVE: To investigate the expression of human-mouse chimeric antibody ch-BD1
      against human bladder cancer and its affinity to human bladder cancer in vitro
      and in vivo. METHODS: Three kinds of mutated fragments of dihydrofolate reductase
      (DHFR) gene were created by techniques of molecular biology to decrease the
      transcriptional activities and then cloned into pDHL-BD1 so as to construct the
      vectors pWSD1-BD1, pWSD2-BD1, and pWSD3-BD1 expressing the human-mouse chimeric
      antibody ch-BD1 against human bladder cancer with decreased expression of DHFR
      gene. These vectors and pDHL-BD1 were transfected into Chinese hamster ovary cell
      (CHO)/DHFR- cell respectively. 72 hours later Northern blotting was used to
      examine their DHFR gene expression. Methotrexate (MTX) of increasing
      concentrations was added into the culture of transfected CHO/DHFR-cells. The ch
      BD1 levels in the supernatants were measured. Purified ch-BD1 was labeled by
      (99m)TcO(4)(-) and added into the serially diluted solutions of human bladder
      cancer EJ cells to examine their radioactivities and calculate their affinity
      constants. EJ cells were injected into the roots of hind limb of 3 Balb/C mice.
      Four weeks later, (99m)TcO(4)(-)-labeled antibody ch-BD1 were injected into the
      rats' caudal veins. Radioimmunoimaging was conducted to examine the distribution
      of the antibody. RESULTS: The sequence of DHFR gene expression levels from strong
      to weak in the constructed vectors was as follows: pDHL-BD1 > pWS1-BD1 > pWS3-BD1
      > pWS2-BD1. When the concentration of MTX was 10(-6) mol/L the expression level
      of ch-BD1 was significantly correlated to the expression level of DHFR gene, the
      lower the baseline expression level of DHFR gene the higher the expression level
      of ch-BD1. After the serially diluted EJ cells were co-incubated with the
      (99m)TcO(4)(-)-labeled antibody ch-BD1 the immunoactivity ratio of ch-BD1 was
      76%, and that of murine monoclonal antibody was 81%; the affinity constant of ch
      BD1 was 3.56 x 10(9) M(-1), and that of murine monoclonal antibody BD1 was 1.22 x
      10(9) M(-1). 6 hours after injection of the (99m)TcO(4)(-)-labeled antibody ch
      BD1 into the mice body it was mainly distributed in the tumor, 22 hours later, it
      was specifically distributed in tumor, and 24 hours later it was still
      concentrated here. CONCLUSION: Decrease of the baseline expression level of DHFR
      gene effectively increases the amplification of MTX to exogenous gene. The human
      mouse chimeric antibody ch-BD1 shows an ideal affinity activity to human bladder
      cancer in vivo and in vitro and has a certain clinical prospect.

PMID- 12812656
TI  - [Effect of berberine on the differentiation of adipocyte].
AB  - OBJECTIVE: To observe the effect of berberine on the differentiation of 3T3-L1
      preadipocytes into adipocytes and to elucidate its mechanism. METHODS: 3T3-L1
      preadipocytes were cultured and then divided into 7 groups into whose media were
      added berberine of the concentrations of 0, 0.1, 1, 10, and 100 micro mol/L, 100
      nmol/Linsulin, and 10 micro mol/L berberine + 100 nmol/L insulin. The
      proliferation of 3T3-L1 preadipocytes was detected by MTT method. The
      accumulation of lipid in the cytoplasm of differentiated adipocytes was observed
      by oil red O staining. The peroxisome proliferation activated receptor gamma2
      (PPARgamma2) mRNA and protein were detected by RT-PCR and Western blotting
      respectively. RESULTS: MTT method showed that the absorbance at 570 nm of 3T3-L1
      preadipocytes increased by 17% (P < 0.01), 36% (P < 0.001), and 22% (P < 0.05) in
      the groups of 1, 10, and 100 micro mol/L berberine, by 53% (P < 0.0001)in the
      group of 100 nmol/L insulin, and by 66% in the group of 10 micro mol/L berberine
      + 100 nmol/L insulin. There were less and smaller lipid droplets in the 3T3-L1
      adipocytes treated with berberine as compared with the untreated control cells
      and only 10% - 20% of the treated cells displayed big lipid drops. RT-PCR showed
      that berberine significantly reduced the expression of PPARgamma2 mRNA by 48% (P
      < 0.01) in the course of 3T3-L1 adipocyte differentiation. Western blotting
      showed that berberine inhibited the expression of PPARgamma2 protein. CONCLUSION:
      Berberine promotes the proliferation of 3T3-L1 preadipocytes, decreases the
      accumulation of lipid drops therein, and inhibits the terminal differentiation of
      adipocyte, which may be associated with its effect on decreasing the expression
      of PPARgamma2 mRNA and protein, suggesting that berberine has advantages in the
      treatment of obesity patients with type 2 diabetes.

PMID- 12812657
TI  - [Treatment of advanced metastatic breast cancer with exemestane, a multicenter
      randomized controlled study of 195 cases].
AB  - OBJECTIVE: To observe the efficacy of exemestane for postmenopausal advanced
      metastatic breast cancer, and to assess its side effects. METHODS: A randomized,
      double-blind, and parallel controlled study was conducted among 195 patients with
      postmenopausal advanced metastatic breast cancer from December 2001 to June 2002.
      Except for the 4 cases who were lost to follow-up, the remaining 191 patients
      were divided into two groups: study group (n = 96, treated with exemestane
      capsule 25 mg and one model tablet of letrozole orally q.d. for 8 weeks), and
      control group (n = 95, treated with letrozole 2.5 mg and one model capsule of
      exemestane orally q.d. for 8 weeks). Physical examination, roentgenography and CT
      were conducted to observe the outcome of the tumor and the level of estrogen was
      tested 2 weeks before and 4 and 8 weeks after the beginning of treatment.
      RESULTS: The effective rate was 44.8% in the study group and 45.3% in the control
      group (P = 0.971). The level of estradiol was 5.17 +/- 6.68 x 10(4) pg/L and 4.19
      +/- 3.06 x 10(4) pg/L in the study group and control group respectively; and was
      3.08 +/- 2.80 x 10(4) pg/L and 2.76 +/- 1.98 x 10(4) pg/L in the study group and
      control group respectively 8 weeks after the beginning of treatment, both
      decreased by 43.7% in comparison with those before treatment (both P < 0.001),
      however, there was no significant difference between the study group and control
      group (P = 0.141). The side effects of exemestane included thirst, giddiness, and
      nausea. CONCLUSION: An effective hormonal medicine, exemestane has good
      therapeutic efficacy in postmenopausal advanced metastatic breast cancer with
      only mild side effects.

PMID- 12812658
TI  - [Curative effect on aggressive B cell non-Hodgkin's lymphoma and relevant
      influencing factors of its prognosis, a study of 203 cases].
AB  - OBJECTIVE: To analyze the curative effect of aggressive B cell non-Hodgkin's
      lymphoma and relevant influencing factors of its prognosis. METHODS: The curative
      effects of aggressive non-Hodgkin's lymphoma which were diagnosed as diffuse
      small cleaved (E), diffuse mixed (F), diffuse large cell (G) or diffuse
      immunoblastic lymphoma (H) pathologically and certified as B cell lymphoma
      immunohistologically and treated with CHOP or other ADM-containing regimens for
      at least 4 cycles from 1993 to 1997 were analyzed. An analysis of the correlation
      of prognosis with different factors was made. RESULTS: The curative effects of
      191 out of the 230 cases were evaluated. 131 (68.9%) patients achieved CR, and 47
      (24.6%) achieved PR. The 6-year overall survival (OS) rates and progress free
      survival (PFS) rates were 51.4% and 43.3% respectively. According to IPI risk
      stratification, the 6-year OS rates were 66.6%, 42.2%, 23.6%, and 10.0% in the
      low-risk, low-intermediate-risk, high-intermediate-risk, and high risk groups
      respectively (P = 0.000 0). The 6-year PFS rates were 59.7%, 30.2%, 16.7%, and
      10.3% in the low-risk, low intermediate risk, high-intermediate-risk, and high
      risk groups respectively. The prognosis analysis showed that OS and PFS were
      significantly correlated with different clinical characteristics such as stage,
      PS, number of extra-nodal lesions, LDH bulky disease, and B symptom. CONCLUSION:
      The treatment with CHOP as its main component has a beneficial effect on
      aggressive B cell lymphoma in low risk group, but is less effective for the low
      intermediate, high-intermediate, and high risk.

PMID- 12812659
TI  - [The effect of insulin on chemotherapeutic drug sensitivity in human esophageal
      and lung cancer cells].
AB  - OBJECTIVE: To discuss the effect of insulin, as a metabolic promoter, on
      chemotherapeutic drug sensitivity in human esophageal and lung cancer cells.
      METHODS: Human esophageal cancer cells NEC and human lung adenocarcinoma cells
      GLC were cultured and then inoculated into the wells. MTT was added.
      Chemotherapeutic drugs, etopside, cisplatin, or 5-fluoto-uracilum was added to
      examine their cytotoxity activity. Then insulin of the final concentration of 5
      mU/ml was added 8 hours before etopside (30 - 40 micro g/ml), cisplatin (2.5
      micro g/ml), or 5-Fu (50 micro g/ml) was added. MTT A value was tested by
      colorimetry to evaluate the number of cancer cells, cell activity, and metabolism
      status so as to reflect the cytotoxity of the anti-tumor agent. Insulin was added
      into the suspension of cancer cells. Flow cytometry was used to detect the cell
      cycle progresses. RESULTS: Insulin alone did not inhibit the cell growth and
      mildly promoted the cell metabolism with the concentration > 5 mU/ml. Insulin
      (2.0 - 15.0 mU/ml) enhanced the chemocytotoxity of etopside (30 micro g/ml) on
      human esophageal and lung cancer cells as indicated by MTT colorimetry. GLC cell
      cycle assay showed that the S phase block induced by etopside, cisplatin and 5-FU
      and the G(2)/M block induced by 5-FU were enhanced by insulin with the increased
      block rates of 80% and 90% respectively. The increased block rate induced by
      insulin in NEC cells was lower than in GLC cells. CONCLUSION: A reversible
      metabolic promoter, insulin enhances the cytotoxity of the chemotherapeutic
      agents. It is possible to increase the growth and metabolism of cancer cells
      first so as to enhance the chemosensibility, and then administer chemotherapeutic
      agents, thus improving their therapeutic effects.

PMID- 12812660
TI  - [Long-term effect of chemotherapy combined with radiotherapy in treatment of
      intracranial germinoma: report of 39 cases].
AB  - OBJECTIVE: To evaluate the long-term effect of chemotherapy combined with
      radiotherapy in treatment of intracranial germinomas. METHODS: Chemotherapy
      combined with radiotherapy was given to 45 patients with intracranial germinomas,
      24 in the pineal region, 8 in the pineal and suprasellar regions, 4 in the
      suprasellar region, and 3 in the pineal region and cerebral ventricle from
      December 1993 to December 1996. Vincristine (VCR), methotrexate (MTX), bleomycin
      and cisplatin were administered for 4 days as a course of treatment. Then blood
      routine examination was taken twice a week and blood biochemical examination was
      taken once a week. A repeat course of chemotherapy was started 4 weeks after if
      no abnormality in blood examination was found. Local radiotherapy was taken with
      low to middle dosage (25 - 35 Gy) 1 - 2 months after the second course of
      chemotherapy. CT and/or MRI examination are made regularly. 39 patients had been
      followed up for 5 - 8 years. RESULTS: Out of the 39 cases followed-up, one with
      the relapsing tumor had undergone operation and radiotherapy 2 years before and
      was given chemotherapy alone without radiotherapy re-relapsed and died in 4
      years. One case relapsed 5 years after chemotherapy and radiotherapy and then was
      given chemotherapy for two more courses with the result of a shrinking of tumor
      by 80%. During the follow-up 37 patients (95%) survived without relapse of tumor
      and resumed their normal work or schooling. CONCLUSION: Chemotherapy combined
      with local radiotherapy with low to middle dosage is the best choice for
      treatment of intracranial germinomas.

PMID- 12812661
TI  - [Prevention of postoperative recurrence of human bladder carcinoma by
      intravesical instillation of immunotoxin, a clinical study].
AB  - OBJECTIVE: To observe the effects of intravesical instillation of immunotoxin
      (IT) on the prevention of recurrence of bladder carcinoma. METHODS: 128 patients
      with superficial bladder carcinoma or bladder carcinoma of T2 stage underwent
      operation, and then were randomly divided into 3 groups 2 - 3 weeks after
      operation to be instilled intravesically with solution of mitomycin (n = 53),
      Calmette-Guerin vaccine (n = 30), or IT (n = 45) once a week for 8 weeks and then
      once every month for 8 months respectively. Cystoscopy, blood routine
      examination, routine urine examination, and liver function test were conducted
      every 3 months. Immunohistochemistry was used to examine 30 samples of resected
      carcinoma. The effects and side effects were observed. Recurrence was verified by
      cystoscopy and/or ultrasonography, CT, and surgery. RESULTS: Out of the 30
      samples of resected bladder carcinoma, 27 were staining positive (+ - + + +) with
      a positive rate of 90%. The binding activity was significantly different between
      the G(1) carcinoma of and the G(3) carcinoma (P < 0.05) and not significantly
      different between the G(1) and G(2) carcinomas and between the G(2) and G(3)
      carcinomas (both P > 0.05). The higher the grade of carcinoma, the stronger the
      binding activity of IT (P < 0.05). The recurrence rate in the first year were
      11.1%, 10.0%, and 15.1% in the IT, BCG, and MMC groups respectively without
      significant difference between any 2 groups (all P > 0.05); and the recurrence
      rate in the 2nd year were 24.4%, 30.0%, and 28.3% in the 3 groups respectively
      without significant difference between any 2 groups (all P > 0.05). The side
      effect rate were 17.8% on the IT group, significantly lower than those in the
      other 2 groups (70.0% and 56.6% respectively, both P < 0.01). However, the side
      effect rates between the BCG group and MMC group was not significantly different
      (P > 0.05). CONCLUSION: IT is more effective on the prevention of recurrence of
      carcinomas with higher malignancy and has fewer side effects. The short-term
      effect of IT is similar to those of BCG and MMC. The activity of IT is associated
      with the grade and not the stage of carcinoma.

PMID- 12812662
TI  - [Inhibition of invasiveness of human mammary carcinoma cell line MDA435 by
      heparanase antisense oligodeoxynucleotide].
AB  - OBJECTIVE: To evaluate the inhibitory effect of heparanase antisense
      oligodeoxynucleotide (AS-ODN) on the invasiveness of human mammary carcinoma cell
      line MDA435. METHODS: The AS-ODN complementary to the start codon region of
      heparanase mRNA and its control, scrambled nonsense oligodeoxynucleotide (NS-ODN)
      were designed and synthesized and phosphorothioated. The ODNs were embedded in
      cationic liposome Lipofectin and transfected into MDA435 cells. The total RNAs
      and proteins were extracted from the cells 48 hours after transfection and then
      semi-quantitative RT-PCR and Western blotting were performed to evaluate the
      heparanase gene and protein expression levels respectively. The invasiveness of
      transfected MDA435 cells were measured quantitatively by Matrigel invasion
      assays. RESULTS: The heparanase gene and protein expression and invasiveness of
      MDA435 cells treated with AS-ODN of different final concentrations were
      significantly decreased compared with that of the controls (P < 0.01). Besides,
      the inhibitory effects were significantly different between the cells treated
      with AS-ODN of different concentrations (P < 0.01). The invasiveness inhibition
      rates were 34.0%, 57.8% and 79.7% at the cells treated with AS-DON of the final
      concentrations of 0.1 micro mol/L, 0.2 micro mol/L, and 0.4 micro mol/L,
      respectively. CONCLUSION: Heparanase AS-DON complementary to the start codon
      region of heparanase mRNA has a significant inhibitory effect on the invasiveness
      of human mammary carcinoma cell line in a dose-dependent manner.

PMID- 12812663
TI  - [Clinical significance of formation and conversion of hematopoietic mixed
      chimerism in nonmyeloablative allogeneic stem cell transplantation].
AB  - OBJECTIVE: To study the clinical significance of formation and conversion of
      hematopoietic mixed chimerism in nonmyeloablative allogeneic hematopoietic stem
      cell transplantation (NAST) in treatment of hematological diseases. METHODS:
      Nonmyeloablative pretreatment was given to 42 patients with hematological
      diseases, 26 males and 16 females with the median age of 37, that were matched
      with the donors in terms of HLA, such as CD3 monoclonal antibody, cyclosporine A,
      cyclophosphamide (CTX) and cytarabine for patients with leukemia among which 6
      were given fludarabine in addition, and CTX and antilymphocyte globulin for
      patients with myeloproliferative disease and aplastic anemia, thus practicing
      nonmyeloablative allogeneic stem cell transplantation (NAST). The incidence of
      graft-versus-host disease (GVHD) and survival were observed. RESULTS: Donor
      recipient hematopoietic cell chimerism was formed in 42 patients, with 18 cases
      of full donor chimerism (FDC) and 24 cases of mixed chimerism (MC). Of the 42
      patients, 10 (23.8%) developed acute GVHD (aGVHD). The incidence of aGVHD in
      group MC (2/24, 8.9%) was significantly lower than that in group FDC (8/24,
      44.4%, P < 0.05). In addition, eight (19.1%) developed chronic GVHD (cGVHD). The
      incidence of cGVHD was also lower in group MC (4/24, 16.7%) in comparison with
      4/18 (23.2%) in group FDC (P > 0.05). There was no difference in recovery time of
      neutrophils and platelets (P > 0.05) between the two groups. Thirty-one patients
      still survived and there was no significant difference between the group FDC and
      MC in terms of survival rate and leukemia relapse rate. CONCLUSION: Compared with
      full donor chimerism, mixed chimerism significantly alleviates the incidence of
      aGVHD and does not delay the hematopoietic reconstitution. It may be an ideal
      model of engraftment that mixed chimerism converts to full donor chimerism within
      several months after NAST.

PMID- 12812664
TI  - [Feasibility study of controlled hypotension induced with combination of propofol
      and desflurane in craniotomy].
AB  - OBJECTIVE: To evaluate the feasibility of controlled hypotension induced with
      combination of propofol and desflurane in craniotomy. METHODS: Thirty-five ASA I
      approximately II patients undergoing elective craniotomy were randomly selected.
      Anesthetic induction was achieved with midazolam, thiopental, fentanyl, and
      vecuronium. Anesthesia was maintained with infusion of propofol and inhalation of
      desflurane. The propofol infusion rate and desflurane inhalation concentration
      were raised during isolation and resection of the tumors so that the mean
      arterial pressure (MAP) was reduced by 30% - 40% and > 50 mm Hg and maintained at
      this level for 30 - 45 min. After the resection of tumor, the propofol infusion
      rate and desflurane inhalation concentration were reduced so as to let the MAP
      increase to normal level. MAP, heart rate (HR), cerebrospinal fluid pressure
      (CSFP), propofol infusion rate, and inhalation concentration of desflurane were
      recorded before controlled hypotension, at the 1st, 3rd, 5th, 10th, 20th and 30th
      minute of the procedure of controlled hypotension, and just before the increase
      of blood pressure and 1, 3, 5, 10, 20, 30, 40 and 50 minutes after controlled
      hypotension. The awakening status was observed. Arterial and jugular bulb venous
      blood samples were taken before, during and after hypotension and the arterial to
      jugular bulb venous oxygen content difference [D(a-jv)O(2)] and cerebral oxygen
      extraction rate (ERO(2)) were measured. RESULTS: The time needed to reach
      controlled hypotension was 6 - 35 minutes and that needed to reach the normal
      blood pressure was 12 - 41 minutes. The propofol infusion rate and inhalation
      concentration of desflurane needed to maintain controlled hypotension were 51
      micro g x kg(-1) x min(-1) +/- 27 micro g x kg(-1) x min(-1) and 6.4% +/- 4.1%
      respectively. HR increased significantly in the initial stage and returned to
      baseline value after 3 - 14 min during the controlled hypotension. CSFP decreased
      significantly after incision of dura mater of brain and during controlled
      hypotension (P < 0.05). The recovery time after weaning from propofol infusion
      and desflurane inhalation until eye opening in response to order and autonomous
      breathing was 25 min +/- 19 minutes. The time needed to regain autonomous
      breathing with the tidal volume > 300 ml/time was 17 min +/- 10 minutes. Compared
      with those before hypotension, the SjvO(2) was increased significantly, and D(a
      jv)O(2) and ERO(2) were decreased significantly during hypotension (P < 0.05).
      CaO(2) and CjvO(2) remained unchanged throughout the process of hypotension (P >
      0.05). CONCLUSION: With low propofol infusion rate and low desflurane inhalation
      concentration, rapid hypotension, rapid recovery of breathing after operation, a
      short recovery time from anesthesia, and decreased CSFP and brain oxygen
      metabolism, controlled hypotension with propofol infusion and desflurane
      inhalation is suitable to intracranial surgery.

PMID- 12812665
TI  - [Treatment of severe steroid-refractory graft-versus-host disease with IL-2R
      alpha chain (CD25) monoclonal antibody].
AB  - OBJECTIVE: To investigate the effects of IL-2R alpha chain (CD(25)) monoclonal
      antibody on severe steroid-refractory graft-versus-host disease (GVHD). METHODS:
      Seventeen patients (18 times) with severe steroid-refractory GVHD were treated
      with intravenous drip of humanized CD(25) monoclonal antibody on day 1, 3 or 4,
      8, 15 and 22. The cumulative scoring of GVHD and status of infection were
      observed, and laboratory tests, including blood counting and blood biochemical
      test were made before and 1, 4, 8, 15, 22, 29, 36, 43 and 50 days after the
      treatment. RESULTS: (1) Eleven of the eighteen case-times (61.1%) got complete
      relief, five (27.8%) GVHD got partial relief, and two (11.1%) failed to get
      relief. (2) Seven case-times (33.3%) had infection. (3) Relapse of GVHD occurred
      in four of the eleven case-times with complete relief (36.4%). (4) No infusion
      related reaction was observed. CONCLUSION: The monoclonal antibody against IL-2
      receptor alpha chain (CD(25)) has a marked effect upon severe steroid-refractory
      GVHD.

PMID- 12812666
TI  - [Expression of chemokine in the labial glands of patients with Sjogren's
      syndrome].
AB  - OBJECTIVE: To investigate the expression of chemokine RANTES (regulated upon
      activation, normal T cell expressed and secreted) and macrophage inflammatory
      protein 1alpha (MIP-1alpha) in the labial glands of patients with Sjogren's
      syndrome (SS) and discuss their involvement in SS etiopathology. METHODS:
      Immunohistochemistry was used to examine the expression of RANTES and MIP-1alpha
      in the specimens of labial gland of 14 cases of primary SS, 7 cases of secondary
      SS (sSS), and 8 cases of controls, including maxillofacial injury and lip cyst.
      RESULTS: The expression rate of RANTES was 86% (12/14) in the pSS group and 71%
      (10/14) in the sSS group, and was 0 in the control group (P < 0.01). The
      expression rate of MIP-1alpha was 86% (5/7) in the pSS group, 71% (5/7) in the
      sSS group, and 25% (2/8) in the control group (P > 0.05). The RANTES and MIP
      1alpha were expressed in the cytoplasm of ductal epithelium and part of
      infiltrated lymphocytes. The positive expression of RANTES was more evident than
      that of MIP-1alpha. CONCLUSION: RANTES and MIP-1alpha may attract the circulating
      lymphocytes towards inflammation site of labial gland so as play a crucial role
      in the pathogenesis of SS etiopathology.

PMID- 12812667
TI  - [A meta-analysis of clinical studies of low volume ventilation in acute
      respiratory distress syndrome].
AB  - OBJECTIVE: Pool the published data of randomized-controlled trials (RCTs) about
      the effect of low volume ventilation in acute respiratory distress syndrome
      (ARDS) and evaluate if low volume ventilation can reduce the mortality of ARDS.
      METHODS: MEDLINE and CBM discs from 1991 to 2001 were selected for the data
      sources. The inclusion criteria were: the subjects were patients with ARDS, the
      study lasted 10 days or more and was RCT, the mortality of ARDS in low volume
      ventilation group was compared with that in traditional ventilation group. The
      data of the studies included were processed with a meta-analysis. RESULTS: 1,435
      cases in 7 studies were included, 5 of 7 studies did not show significant
      different mortalities between the two treatment groups and 2 studies indicated
      the low volume ventilation could improved the survival of ARDS. The mortalities
      of ARDS in low tidal volume ventilation group and traditional ventilation group
      were 35.98% (258/717) and 42.62% (306/718) respectively. The combined OR of all
      studies was 0.754 (95% CI 0.610 - 0.933), P < 0.01. CONCLUSION: Low volume
      ventilation benefits the survival of ARDS. It is worth application in clinical
      practice.

PMID- 12812668
TI  - [Redistribution of epidermal stem cells in wound edge in the process of re
      epithelialization].
AB  - OBJECTIVE: To study the redistribution of epidermal stem cells in regenerating
      wound tissues, and to elucidate the role of epidermal stem cells during wound
      repair. METHODS: 80 circular full-thickness wounds were produced on both sides of
      the back in 20 male Wistar rats (4 wounds in each animal). Then the 80 wounds
      were randomly divided into 2 groups: group A (treated with sulfadiazine silver-
      sulfadiazine zinc cream, n = 40) and group B (without any treatment, n = 40). The
      infection and healing process of the wounds were observed with naked eyes. Five
      mice were killed one time 3, 7, 14, and 21 days after the wounding. Two wounds
      with surrounding normal skin tissues were collected from each mouse. Routine
      histological examination was conducted with HE staining. Beta(1) integrin and
      keratin19 (K19), markers of epidermal stem cells, were employed to determine the
      distribution of epidermal stem cells with streptavidin-peroxidase (SP)
      immunohistochemical method. RESULTS: The healing rate of wounds was 80% (32/40)
      in group A, and 60% (24/40) in group B. No beta(1) integrin and K19 positive
      cells was found in the granulation tissue of all wounds in these 2 groups at any
      time point during the healing process. However, a few beta1 integrin and K19
      positive cells, bearing no anatomic relation with the epidermal stem cells in the
      basal layer, were found scattering in the stratum spinosum and stratum granulosum
      of the epidermis on the wound edges. The closer to the wound the more
      concentrated the beta(1) integrin and keratin19 positive cells. Their numbers
      increased gradually along with the shrinking of the wound surface until the wound
      completely healed. The numbers of the beta(1) integrin and keratin19 positive
      cells decreased gradually after epithelialization. The numbers of the beta(1)
      integrin and keratin19 positive cells were obviously lower in the infected wounds
      than in the uninfected wounds. CONCLUSION: Epidermal stem cells participated in
      the healing of wound. The function of redistribution of epidermal stem cells in
      wound edges seems to promote the re-epithelialization of granulating wounds.

PMID- 12812669
TI  - [Effect of exogenous epitopes of helper T lymphocyte on humoral immunity of HBV S
      gene DNA immunity].
AB  - OBJECTIVE: To study the effect of exogenous epitope of helper T lymphocyte (HTL)
      on humoral immunity of HBV S gene DNA immunity. METHODS: Two universal HTL
      epitopes, amino acid residue (aa) 830-843 of the tetanus toxoid (TTE) and
      artificial epitope (PADRE), and 3 unique epitopes, aa1-20 of tubercle bacteria
      hot shock protein 65 (TBE), aa54-65 of rubella protein E2-4 (ME) and aa35-48 of
      trachoma hot shock protein 60 (CE) were chosen. Eukaryotic expression vectors
      were constructed by inserting single or multiple exogenous epitopes in HBV S gene
      just after the initial code of translation. BALB/c mice were inoculated with 100
      micro g of recombinant DNA per mouse, and given boost inoculation for 3 times
      with 3-week interval. Mouse blood were collected one month just after the third
      boost inoculation. Anti-HBs was detected using Abbott test kits. RESULTS: HBV S
      eukaryotic gene expression vectors, pHB and 6 exogenous HTL epitope HBV S gene
      vectors, pHB-TBE, pHB-PADRE, pHB-TTE, pHB-MTE2, pHB-MTE3 and pHB-MTE5 were
      constructed successfully with anti-HBs level (IU/L) of 10 +/- 5, 5 +/- 5, 49 +/-
      7, 29 +/- 6, 16 +/- 8, 23 +/- 7 and 28 +/- 8 respectively. Among 3 single
      epitopes, TTE and PADRE had obviously effect on promoting the anti-HBs response
      of HBV S gene, while TBE had no promoting effect. All of the 3 multiple epitopes
      were shown the effect of immune promoting. CONCLUSION: Some exogenous HTL
      epitopes had obviously effect on promoting the anti-HBs response of HBV S gene.
      Multiple epitopes also had humoral immunity promoting effect, but there was no
      synergic effect among their own HTL epitopes. PADRE might be an important
      candidate for new efficient HB vaccine. The multiple epitope cluster consisted
      form 5 exogenous epitopes might be an important candidate for the reinoculating
      HB vaccine or therapy HB vaccine.

PMID- 12812670
TI  - [An experimental study on the effect of Maotai liquor on the liver].
AB  - OBJECTIVE: To explore the effect on liver and the mechanism of preventing hepatic
      fibrosis by drinking Kweichow Moutai liquor (Maotai). METHODS: (1) After ingested
      with Maotai for 56 days consecutively, the male SD rats were decollated for
      detecting metallothioneins and MDA content in liver tissues; (2) Culturing rat
      hepatic stellate cell (HSC) and human HSC in vitro, observing the effect of
      Maotai on HSC's proliferation and collagen synthesis; (3) After male SD rats were
      ingested with Maotai for 14 weeks consecutively, the livers were harvested for
      pathohistological examination. RESULTS: (1) Metallothioneins content in the liver
      of Maotai-induced rats increased by 22 folds, the production of hepatic lipid
      peroxide, MDA was significantly decreased (P < 0.05) in Maotai-induced animals
      suffering from CCL4; (2) Maotai demonstrate obvious inhibitory effect against
      proliferation of HSC, and the inhibition was concentration-dependent. gene
      expression and protein secretion of collagens could also be inhibited by Maotai;
      (3) In control alcoholic group, typical cirrhosis of liver was shaped. In Maotai
      group, however, though fatty degeneration of hepatocytes and mild fibrosis of
      interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found.
      CONCLUSION: It might be an important mechanism of interfering hepatic fibrosis
      progressing that Maotai induces the increase of metallothioneins content in the
      liver, inhibits the activation HSC and the synthesis of collagen protein.

PMID- 12812671
TI  - [PKC-dependent activation of P44/42 MAPKs and HSP70 in signal transduction
      pathways during hepatocyte ischemic preconditioning].
AB  - OBJECTIVE: To investigate the significance of PKC, P44/42 MAPKs and HSP70 signal
      transduction in IP. METHODS: Through an in vivo rat liver IP model, PKC
      inhibitor, activator and MEK inhibitor were utilized to analyze the
      phosphorylation of PKC and P44/42 MAPKs. HSP expression, AST/ALT concentration,
      cellular structure and ultrastructure were also observed. All the data were
      statistically analyzed. RESULTS: Compared with the control without IP, the
      phosphorylation of PKC was significantly increased in IP treated models and PKC
      activated group (P < 0.01) and P44/42 MAPKs and the expression of HSP were also
      obviously increased. In contrast, opposite changes were found in PKC or MEK
      inhibited groups, the phosphorylation PKC was decreased in PKC inhibited group (P
      < 0.01). CONCLUSION: The model has shown that PKC activation plays a pivotal role
      in the activation of P44/42 MAPKs pathway that participates in the preservation
      of liver cells. At the same time, HSP expression is regulated by signals in
      P44/42 MAPKs pathway.

PMID- 12812672
TI  - [Complications in selective coronary angiography: analysis of 9196 cases].
AB  - OBJECTIVE: To study the incidence rates, risk factors, prevention and treatments
      of complications of selective coronary arteriography. METHODS: A retrospective
      survey was conducted on the data of the incidence and annual distribution
      characteristics of complications among 9 196 cases that underwent selective
      coronary arteriography performed October 1987 to December 2000, and analyze the
      risk factors and prevention and treatment of these complications. RESULTS: The
      total complication rate was 1.33%. The procedure-related mortality rates were
      0.02%. The incidence rate of non-fatal Q wave myocardial infarction, coronary
      artery spasm, severe arrhythmia, severe contrast allergic reaction, peripheral
      vascular complication, and heart failure in coronary arteriography was 0.01%,
      0.13%, 0.29%, 0.04%, 0.35%, and 0.08%, respectively. No emergent coronary artery
      bypass surgery was required in patients with coronary arteriography. The
      independent risk factors of the complications of coronary arteriography included
      unstable angina, coronary multivessel disease, left main coronary artery disease
      and heart failure. CONCLUSION: The complication rate of coronary arteriography
      decrease with the accumulation of experience. The complication rate in this group
      is lower than in other reports probably due to strictly selecting of indication
      and active prevention and treatment of complications.

PMID- 12812673
TI  - [A study on the relationship of Helicobacter pylori, gastrin and gastroesophageal
      reflux disease].
AB  - OBJECTIVE: To study the relationship of Helicobacter pylori, lower esophageal
      sphincter pressure and gastrin in gastroesophageal reflux disease, to evaluate
      the effect of Helicobacter pylori on gastroesophageal reflux disease. METHODS: 20
      patients were underwent 24-hour ambulatory esophageal pH monitoring to confirm
      the diagnosis of gastroesophageal reflux disease, and their lower esophageal
      sphincter pressure was measured by esophageal manometry. The patients were
      diagnosed endoscope negative GERD and endoscope positive GERD by endoscopy, and 3
      biopsy specimens obtained from the gastric antrum at the same time were used for
      Helicobacter pylori culture, rapid urease test and Warthin-Starry stain. Hp
      infection was affirmed when at least two of the three tests were positive, then
      the patients were divided into Hp-negative group and Hp-positive group. Fasting
      serum gastrin concentration was determined by radioimmunoassay in 13 patients.
      RESULTS: Hp-positive patients were 8 (male 4, endoscope negative GERD 2, mean age
      55 +/- 9), Hp-negative patients were 12 (male 10, endoscope negative GERD 3, mean
      age 55 +/- 10). 13 of these patients were performed fasting serum gastrin
      measurement. The mean lower esophageal sphincter pressure, gastrin concentration
      and 24-hour pH monitoring DeMeester score in Hp-positive patients group were
      11.25 mm Hg, 87.437 pg/ml and 72.30 respectively, and those in Hp-negative
      patients group were 13.75 mm Hg, 88.725 pg/ml and 55.64. Between the two groups,
      there was no significant difference in LESP, gastrin and DeMeester score (P =
      0.193, P = 0.932 and P = 0.479); There was no correlation between LESP and
      gastrin, while serum gastrin level is associated strongly with DeMeester score (r
      = 0.902, P < 0.01). CONCLUSION: The study showed that Helicobacter pylori had no
      effect on LESP by gastrin, however serum fasting gastrin concentration and
      DeMeester score were associated with each other.

PMID- 12812674
TI  - [Relationship between three neuropsychological tests and cerebral glucose
      metabolism in Alzheimer's disease].
AB  - OBJECTIVE: To study the relationship between the scores of 3 neuropsychological
      scales: MMSE, extended scale of dementia (ESD) and Blessed dementia scale (BDS)
      and cerebral glucose metabolism in Alzheimer's disease (AD) indicated by positron
      emission tomography (PET). METHODS: Brain scanning was performed with SIEMENS
      ECAT 47 PET scanner among 21 AD patients, aged 60 - 83 (10 mild, 6 moderate, and
      5 severe), and 15 healthy persons, aged 57 - 73. The ratio of mean radioactivity
      of cerebral lobe to that of cerebellum as semi-quantitative parameters was used
      to evaluate the cerebral glucose metabolism. Cognitive function was assessed by
      three neuropsycholigical scales: MMSE, ESD and BDS. RESULTS: The average MMSE
      score was 13.3 +/- 6.3 (range 2 - 25), the average ESD score was 120.5 +/- 54.8
      (range 28 - 200), and the average BDS score was 4.7 +/- 3.1 (range 0.5 - 10) in
      the AD patients. The decreases of glucose metabolism in parietal, frontal and
      temporal lobes were significantly positively correlated with MMSE and ESD scores,
      and negatively correlated with BDS scores in AD patients (P < 0.05). The
      correlations between MMSE and ESD (r = 0.886), MMSE and BDS (r = -0.763), and ESD
      and BDS (r = -0.773) were significant in AD patients (all P < 0.01). Taking the
      ratio of radioactivity of cerebral lobe to that of cerebellum as an independent
      variable X, the MMSE, ESD and BDS scorsas dependent variable Y, three regression
      equations were established as follows: Y = 40.11 * X- 25.32, Y = 309.19 * X-
      180.9, Y = 19.97 - 16.53 * X. The independent variable entering the three
      regression equations was always the ratio of radioactivity of left parietal lobe
      to that of cerebellum. The ratio of radioactivity of left parietal lobe to that
      of cerebellum was a significant predictor for cognitive dysfunction measured by
      MMSE, ESD and BDS in AD patients (P < 0.01). CONCLUSION: MMSE, ESD and BDS scores
      correlate well with impaired cerebral glucose metabolism in AD. The function of
      left parietal lobe may play an important role in the progress of the disease.
      MMSE, ESD and BDS are good measures for cognitive dysfunction.

PMID- 12812675
TI  - [Cochlear implantation in patients with inner ear malformations, clinical
      analysis of 25 cases].
AB  - OBJECTIVE: To explore the clinical experience of multi-channel cochlear
      implantation in patients with bilateral inner ear malformations. METHOD: Multi
      channel cochlear implantation was conducted among 180 patients from 1997 to 2001.
      Twenty-five of them, being with inner ear malformations, were given hearing and
      speech rehabilitation including sound detection, word discrimination, auditory
      comprehension and spoken language skill development. A follow-up lasting 4 - 24
      months was conducted after the operation. A retrospective analysis was performed
      among these 25 patients to observe the surgical outcomes and mapping
      characteristics after surgery. RESULTS: (1) All patients restored their auditory
      sensations after the operation. (2) Stapedial gusher was found in 13 cases with
      inner ear malformations, especially those with Mondini malformation, much more
      frequently than among the patients with other malformations. (3) Most of the
      action electrodes were inserted in the "cochleostomy" in full length, only 2
      pairs of them remained outside of the "cochleostomy". (4) No serious
      complications occurred after implantation. (5) The impedance of the electrodes, T
      level and C level were higher in the 25 cases than in the normal cochlear
      implantation, however, with the hearing similar hearing threshold. (6) After
      training, the abilities of speech discrimination and spoken language were
      improved in comparison with those before operation. CONCLUSION: The cochlear
      implantation can be performed safely in patients with bilateral inner ear
      malformations. The primary outcome of cochlear implantation in hearing
      rehabilitation is similar for both the patients with inner ear malformations and
      those with normal cochlear structure.

PMID- 12812676
TI  - [Completely reversed acute rejection episodes do not influence the long-term
      renal allograft survival].
AB  - OBJECTIVE: To assess the influence of times and duration of acute rejection
      episodes and the effect of antirejection therapy in renal transplantation
      recipients on the long-term survival of renal allograft. METHODS: The clinical
      data of 946 patients who received renal transplantation were analyzed to analyze
      the survival of renal allograts in different conditions: times of rejection
      episode, time of onset of acute rejection, and effect of antirejection therapy by
      life table and Wilcoxon test, and to identify the risk factors through Cox
      regression analysis. RESULTS: During the follow-up with a range of 3
      approximately 158 months acute rejection occurred in 172 patients. The 946 cases
      of kidney transplantation were divided into rejection free group (NAR, n = 774),
      one time rejection group (1AR, n = 159), and twice and more rejection group (2AR,
      n = 13) according to the times of rejection. The 1AR group was subdivided into
      completely reversed group (CAR) and incompletely reversed group (1AR). The 1AR
      cases were subdivided into early-stage rejection group (EAR, with episode within
      90 days after transplantation, n = 112) and late-stage rejection group (LAR, with
      episode 90 days later transplantation, n = 47) according to the onset time of
      rejection episode. The five-year survival rate was 70.9% in the AR group (n =
      172) and was 93.3% in the NAR group (P < 0.000 1). The ten-year survival rate of
      renal allografts was 29.8% in the AR group, and was 83.3% in the NAR group (P <
      0.000 1). The 5-year survival rate of renal allograft was less than 30% in the
      2AR group, significantly lower than those in the NAR and IAR groups (P < 0.000 1
      and P< 0.003). The 5-year survival rate of renal allograft was 89.0% in the EAR
      group, significantly higher than that in the LAR group (48.9%, P < 0.000 1). The
      8-year survival rate was 84.3% in the EAR group, significantly higher than that
      in the LAR group (32.1%, P < 0.000 1). Both the survival rates of renal allograft
      in the EAR and LAR groups were significantly lower than that in the NAR group (P
      = 0.025 and P < 0.000 1). The condition had been completely reversed in 95
      patients and incompletely reversed in 54 patients, and failed to be improved in
      10 patients out of the 159 cases in the IAR group after antirejection therapy.
      The 5-year survival rate of renal allograft was 93.9% in the CAR group,
      significantly higher than that in the IAR group (63.1%, P < 0.000 1) but not
      significantly different from that in the NAR group (P = 0.96). The 8-year
      survival rate of renal allograft was 89.2% in the CAR group, significantly higher
      than that in the IAR group (41.4%, P < 0.000 1) but not significantly different
      from that in the NAR group (P = 0.96). The time of rejection onset was not the
      main factor effecting survival rate of grafts. The main risk factor influencing
      the long-term survival of renal allograft was the therapeutic effect after the
      onset of rejection with a risk rate of 3.14. CONCLUSION: The acutely rejected
      renal allografts have poor long-term survival. The long-term survival rate of
      renal allograts with acute rejection that occurs only once and is completely
      recovered after antirejection therapy is not significantly different from that of
      the renal allografts in NAR group.

PMID- 12812677
TI  - [One-stage surgical management for spinal tuberculosis].
AB  - OBJECTIVE: To evaluate the clinical efficacy of one-stage surgical management for
      spinal tuberculosis. METHODS: Fifty-seven patients with thoracic, thoracolumbar
      and lumbar spinal tuberculosis were treated surgically by a single stage
      procedure from Jan 1996 to Jan 2001, including anterior resection, interbody
      outografting and anterior instrumentation in 35 cases, posterior debridement and
      posterior instrumentation in 16 cases, and posterior instrumentation and anterior
      resection plus interbody autografting in 6 cases. Titanium-alloy spinal implants
      were used in 38 cases and stainless steel implants in other 19 cases. Except for
      three patients, other 54 patients were followed up for one to five years (mean
      2.2 years). RESULTS: All these patients had their incision healed by first
      intention without chronic infection or sinus formation, and no recurrence of
      spinal tuberculosis was noted in any patient during the follow-up period.
      Kyphosis correction were achieved by 21.6 degrees on the average postoperatively.
      There was a mild loss (2 degrees - 4 degrees) of kyphosis correction during
      follow-up period. Spinal solid fusion at the interface between the graft and
      adjacent vertebral bodies was shown radiologically in 3.8 months on the average.
      CONCLUSION: One-stage surgical management has more advantages in that it can
      completes all the aspects of surgical treatment for spinal tuberculosis. Anterior
      or posterior instrumentation with titanium-alloy or stainless steel spinal
      implants is safe, The selection of one-stage surgical procedure should be planed
      individually.

PMID- 12812678
TI  - [Effect of volume replacement with hydroxyethyl starch solution for blood loss on
      splanchnic oxygenation in patients undergoing cytoreductive surgery for ovarian
      carcinoma].
AB  - OBJECTIVE: To investigate the effect of medium molecular weight hydroxyethyl
      starch solution (HES) administered as replacement for estimated blood losses
      (EBL) during cytoreductive surgery for ovarian carcinoma on splanchnic
      oxygenation. METHODS: Cytoreductive surgery was operated upon forty-two patients
      with ovarian carcinoma. As soon as the EBL was higher than 10% but less than 20%
      of the estimated blood volume, the patients were randomly assigned to receive a
      volume of lactated Ringer's solution (LRS) equal to three times the EBL (LRS
      group, n = 22) or a volume of 6% HES equal to the EBL (HES group, n = 20). Tissue
      oxygenation was assessed indirectly by measuring the tonometric parameters of
      stomach, including difference between gastric intramucosal PsCO(2) and arterial
      PaCO(2) (Ps-aCO(2) gap), gastric intramucosal pH (pHi) and arterial lactate acid
      concentration 30 min after induction of anesthesia (baseline value), 1 h and 2 h
      after skin incision, and at the end of surgery. RESULTS: At the end of surgery,
      the Ps-aCO(2) gap was 8.7 mm Hg +/- 1.6 mm Hg in the HES group, significantly
      lower than that in the LRS group (18.74 mm Hg +/- 4.4 mm Hg, P < 0.01), while the
      pHi in the HES group was 7.30 +/- 0.05, significantly higher than that in the LRS
      group (7.21 +/- 0.07, P < 0.01). There was no significant difference in arterial
      lactate acid concentration between the two groups. CONCLUSION: In patients
      undergoing major surgery, volume resuscitation with medium molecular weight HES
      improves the splanchnic blood flow and tissue oxygenation.

PMID- 12812679
TI  - [Effects of atorvastatin on the proliferation and collagen synthesis of rat
      cardiac fibroblasts].
AB  - OBJECTIVE: To investigate the effects of atorvastatin on the proliferation and
      collagen synthesis of rat cardiac fibroblasts (CFs). METHODS: Isolated and
      cultured CFs of neonatal Sprague-Dawley (SD) rats were isolated and cultured. The
      DNA synthesis of CFs was measured by (3)H-TdR uptake test. CFs proliferation was
      measured by thiazolyl blue (MTT) assay. Cell cycle distribution was determined
      with flow cytometer (FCM). Collagen synthesis was measured by 3H-proline uptake
      test. RESULTS: (1) The (3)H-TdR uptake in the 10(-7) mol/L, 10(-6) mol/L, 10(-5)
      mol/L, and 10(-4) mol/L atorvastatin groups was (cpm/5,000 cells) 314 +/- 68, 253
      +/- 52, 201 +/- 53, and 170 +/- 48 respectively, all significantly lower than
      that of the control group (378 +/- 65, all P < 0.001). (2) MTT colorimetry showed
      that the A(490) values were 0.288 +/- 0.008, 0.252 +/- 0.007, 0.225 +/- 0.008,
      and 0.216 +/- 0.013 respectively in the 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L
      and 10(-4) mol/L atorvastatin groups, all significantly lower than that in the
      control group (0.311 +/- 0.005, all P < 0.01). (3) The percentage of cells in
      G(0)/G(1) phase was 54.8% +/- 2.5%, 61.4% +/- 2.7%, 70.4% +/- 3.2%, and 82.0% +/-
      4.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups, all significantly higher
      than that in the control group (46.5 +/- 2.9, all P < 0.01). The percentage of
      cells in S phase was 18.8% +/- 2.3%, 15.8% +/- 2.1%, 12.5% +/- 1.8%, and 7.3% +/-
      2.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups, all significantly lower
      than that in the control group (23.1% +/- 2.0%, all P < 0.01). The percentage of
      cells in G(2)/M phase was 26.5% +/- 0.8%, 22.8% +/- 1.2%, 17.2% +/- 1.4%, and
      10.7% +/- 2.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups respectively, all
      significantly lower than that in the control group (30.5% +/- 1.4%, all P <
      0.01). The proliferation index (PI) was 45.3% +/- 2.5%, 38.6% +/- 2.7%, 29.6% +/-
      3.2%, and 18.0% +/- 4.0% in the 10(-7) - 10(-4) mol/L atorvastatin groups
      respectively, all significantly lower than that in the control group (53.5% +/-
      2.9%, all P < 0.01). (4) The (3)H-proline uptake was (cpm/5 000 cells) 422 +/-
      59, 332 +/- 67, 252 +/- 53, and 184 +/- 48 in the 10(-7) mol/L, 10(-6) mol/L, 10(
      5) mol/L, and 10(-4) mol/L atorvastatin groups respectively, all significantly
      lower than that in the control group (566 +/- 62, all P < 0.01). CONCLUSION:
      Atorvastatin inhibits effectively the proliferation of cultured rat CFs and the
      collagen synthesis therein, which may play a role in the regression of heart
      remodeling.

PMID- 12812680
TI  - [Na+/dicarboxylate cotransporter expression changed with aging in basolateral
      membrane of the renal tubular epithelial cells].
AB  - OBJECTIVE: To study the change with aging of Na(+)/dicarboxylate cotransporter
      (NaDC3) expression in basolateral membrane of epithelial cell in proximal renal
      tubules in rat and human being. METHODS: Six groups of 6 Wistar rats at the age
      of: 1 day, 7 days, 1 month, 3 months, 12 months, and 24 months respectively were
      killed and their kidneys were taken to be examined immunohistochemically. Samples
      of kidney from 15 normal human beings, 5 in the group aged 6 - 8, 5 in the group
      aged 32 - 44, and 5 in the group aged 63 - 65, were examined
      immunohistochemically. Northern blotting, and Western blotting were used to
      detect the mRNA and protein expression of NaDC3 in renal tissues from both rats
      and human beings. The concentrations of citrate in both plasma and urine of the
      rats were tested. RESULTS: (1) The concentration of citrate in urine was340 mg/L
      +/- 144 mg/L in rats at the age of 7 days and declined gradually with aging
      significantly to the value of 59 mg/L +/- 27 mg/L in the rats aged 24 months (P <
      0.05). The concentration of citrate in rat plasma was 85 mg/L +/- 45 mg/L and
      then declined gradually with aging significantly to the value of 31 mg/L +/- 20
      mg/L at the age of 24 months (P < 0.05). (2) The renal expression of both mRNA
      and protein of NaDC3 increased with aging in rats and human beings (P < 0.01).
      (3) Located in the basolateral membrane of epithelial cell in the proximal renal
      tubule, NaDC3 expression began to be detected in rat since at the age of 7 days
      and then increased gradually in comparison with that at the day 7 (P < 0.01).
      However, the value of NaDC3 expression at the age of 24 months was not
      significantly different from that at the age of 12 months (P > 0.05). Similar
      results were also observed in normal human beings. CONCLUSION: NaDC3 may play a
      role in the aging process through the metabolic mechanism of citrate, etc.

PMID- 12812681
TI  - [Experimental study of anti-infective reconstructed bone xenograft].
AB  - OBJECTIVE: To develop a new type bone graft material that can be used as primary
      graft in contaminated even infected bone defect. METHODS: Anti-infective
      reconstructed bone xenograft (ARBX) was developed by combining reconstructed bone
      xenograft (RBX) with gentamycin and gelatin. One piece of ARBX was implanted in
      the muscle pouch in right thighs of 32 mice. The implanted ARBX and surrounding
      soft tissues were taken out from the mice at different time point to make into
      homogenate and the concentration of released gentamycin in the supernatant and
      the diameter of the bacterial inhibition ring of each specimen were tested. One
      piece of ARBX was implanted into the muscle pouch at the right thigh of 16 mice
      and one piece of RBX was implanted into the muscle pouch at the right thigh of
      another 16 mice. Fourteen days after the grafts and surrounding tissues were
      taken out to be examined histologically or made into homogenate to test the
      alkaline phophatase (ALP) activity. Bone defect was made in the bilateral radii
      and then Staphylococcus aureus was injected and debridement was conducted. 10
      pieces of ARBX were implanted into the bone defect at the left radius and 10
      pieces of RBX were implanted into the bone defect at the right radius. The defect
      was then fixed and the wound was sutured. Gentamycin was injected for 1 week. Six
      months later X ray examination was conducted to the radius, then the radius was
      taken and half of specimens were examined histologically and half of them was
      made into homogenate to examine the amount of Staphylococcus aureus. Defect was
      made in the right tibia of 25 rabbits and Staphylococcus aureus injected therein.
      Then the rabbits were divided into 5 groups of 5 individuals: group 1 (3 pieces
      of ARBX were implanted), group 2 (3 pieces of RBX were implanted and gentamycin
      was used locally), group 4 (3 pieces of RBX were implanted and gentamycin was
      injected intramuscularly), and group 5 (control group, without born grafting).
      Eight weeks after, radiological, histological, and bacteriological methods were
      used to observe the recovery of bone defect and amount of Staphylococcus aureus.
      RESULTS: Gentamycin was released slowly from the ARBX and the effective bacterium
      inhibiting concentration lasted 30 days. There was no significant difference in
      osteoinductive activity and related ALP activity between the mice implanted with
      ARBX and RBX. The bone defect of the dogs implanted with ARBX recovered better
      than that of the dogs implanted with RBX; osteomyelitis was found in the
      specimens from the bone defect implanted with RBX and not in the specimens
      implanted with ARBX, and the positive rate of Staphylococcus aureus was lower in
      the specimens implanted with ARBX than in the specimens implanted with RBX. 8
      weeks after the implantation the Norden score of osteomyelitis was the lowest in
      the rabbits of group 1 (P < 0.01). The bone defect recovered better in the
      rabbits of groups 1 and 2. The number of Staphylococcus aureus in the bone defect
      in rabbits of group 1 was significantly smaller than that in the rabbits of group
      2 (P < 0.05), and was very significantly smaller then in the rabbits of the other
      3 groups (P < 0.01). CONCLUSION: ARBX has strong oeteoinductive and anti
      infective abilities. It can be used in primary bone grafting to treat
      contaminated even infected bone defect.

PMID- 12812682
TI  - [The role of nuclear factor kappa B in secretion of interleukin-8 by gastric
      cancer cell line SGC 7901 induced by Helicobacter pyiori].
AB  - OBJECTIVE: To investigate the role of nuclear factor kappaB (NF-kappaB) in the
      gastric inflammation induced by Helicobacter pylori (H. pylori). METHODS: SGC
      7901 was transfected with IkappaB (NF-kappaB inhibitor gene) by electroporation,
      (beta)lacZ activity assay was used to examine transfected efficacy. Expression of
      IkappaB was assessed by Western-blot. Different concentration of live and heat
      killed Hp (ATCC 43504) and supernatant of liquid culture were cocultured with
      SGC7901-IkappaB and its negative control SGC7901- neo. Activation of
      intracellular NF-kappaB was examined by electrophoretic mobility shift analyses
      (EMSA) and luciferase report gene assay at different time point. IL-8 levels were
      measured by ELISA at different time point. RESULTS: IL-8 release was evident 4
      hours after infection of SGC-7901-neo with H. pylori, and this effect was dose
      time dependent. SGC-7901-IkappaB in which NF-kappaB has not been activated could
      not secret IL-8 after infection with H. pylori. CONCLUSION: Secretion of IL-8 by
      gastric epithelial cell upon H pylori infection is dependent on activation of NF
      kappaB.

PMID- 12812683
TI  - [Rural WONCA Congress. The world debate on rural medicine at Santiago de
      Compostela].

PMID- 12812684
TI  - [Detection of cognitive impairment in the population of persons older than 64
      years: first phase of the Cuida'l project].
AB  - OBJECTIVE. To know the proportion of people with positive result in test. Design.
      Cross sectional study in 53 health centers. SETTING. Primary care. PARTICIPANTS:
      Aleatory sample of non-institutionalised, elder than 64 years patients attended
      in the 53 health centers. MEASUREMENTS:  VARIABLES: age, sex, civil status, and
      educational level. The detection of cognitive deterioration (CD) was carried out
      in primary care units with Folstein's Mini Mental Test (MMT) and the Isaacs Set
      Test in case of illiteracy. Cut-off points 24 and 27 respectively. CD predictor
      variables analysis with logistic regression. MAIN RESULTS: The tests were applied
      to 4,467 individuals (56.1% females). There were found as possible cases of CD
      399 patients (72.2% with MMSE). Positive percentage was 7.78% (95% CI, 5.69%
      10.99%) in males and 9.45% (95% CI, 7.31%-12.43%) in female, adjusting with
      indirect method, according to the 1996 Catalonia list of inhabitants. Significant
      predictor factors were found with the multivariate analyses: primary educational
      level in front of illiteracy (OR=1.40, 95% CI, 1.13%-1.74%) and age-groups: 74-79
      years, 75-79 years and y >= 80 years in front of <70 years old (OR=1,48, 95% CI,
      1.02%-2.14%, OR=2.29; 95% CI, 1.60%-3.28% and OR=5,02; 95% CI, 3.59%-7.03%
      respectively). CONCLUSIONS: The cognitive deterioration prevalence increases with
      age and it is less frequent in individuals with higher studies Using MMSE and Set
      Test we found several possible cases of cognitive deterioration in our
      population.

PMID- 12812685
TI  - [Commentary: The importance of epidemiological studies of cognitive impairment].

PMID- 12812686
TI  - [Reliability and validity of the Spanish version of the MOS-SF-30 to assess the
      health related quality of life in people infected by HIV].
AB  - OBJECTIVES: To assess the psychometric properties of the health related quality
      of life questionnaire of the Medical Outcomes Study-short form 30 items (MOS-SF
      30). DESIGN: Cross sectional study.Setting. Urban university hospital.
      PARTICIPANTS: A hundred HIV+ subjects (28 asymptomatic, 35 symptomatic and 37
      with AIDS). MEASUREMENTS: HRQoL questionnaire MOS-SF30, clinical (CDC stage) and
      immunological measures (CD4, viral load). Results. MOS-SF30 questionnaire
      (Spanish version) presents adequate internal consistency (between 0.84 to 0.91
      for the different subescales), yielding also total Cronbach's alpha of 0.93.
      Concurrent validity has been contrasted through the medical measures. Total
      punctuation of the scale was able to distinguish the subjects between the
      different stages of the HIV infection and to distinguish those with an
      undetectable viral load. CONCLUSIONS: Spanish version of the MOS-SF-30 seems to
      be a valid measure for the evaluation of the perceived health status and quality
      of life in people living with HIV.

PMID- 12812687
TI  - [Models to explain and predict medical case-loads: their use in calculating the
      maximum family medicine list that allows at least ten minutes per consultation].
AB  - OBJECTIVE: To calculate the maximum family medicine list that gives at least ten
      minutes per consultation.Design. Transversal. SETTING: Three health centres.
      SUBJECTS: 45 826 inhabitants. MEASUREMENTS: We used the appointments made at
      three centres to calculate the annual time employed per patient and we adjusted
      it to allocate a minimum of ten minutes per consultation. We established a cubic
      regression model to predict the mean case-load per age of patient in general
      medicine and calculated the maximum list if 70% of the working day were dedicated
      to care. The results contrasted two centres with greater nursing involvement and
      one with less. We showed the R2 coefficients. We calculated the maximum lists for
      the health centres of Navarra and showed them in five clusters worked out on the
      basis of the percentage of patients >=65. RESULTS: Age explained 86.1% of
      variability in mean case-load at each age (84% in children and 93.5% in adults).
      According to the mean percentage of those >=65 years old, the average maximum
      lists for centres with more or less nursing involvement are as follows: 7.0%>=65
      (2025 and 1989); 14.0% (1834 and 1715); 21.2% (1691 and 1558); 27.0% (1648 and
      1460), 34.0% (1560 and 1340). CONCLUSION: To a great extent, age explains the
      variability in case-load and lets us calculate the maximum number of patients on
      the list that still ensures a minimum time for each consultation.

PMID- 12812688
TI  - [Document of wishes stated in advance: attitudes of primary care patients].
AB  - OBJECTIVE: To find the attitude of health centre patients to the Document of
      Wishes stated in Advance (DWA).Design. Descriptive cross-sectional study using a
      specially designed questionnaire. Setting. Urban health centre in Palma de
      Mallorca. PARTICIPANTS: 132 users of a primary care clinic in Palma de Mallorca,
      seen between 21/6/2002 and 15/7/2002. Criteria for exclusion: <40 years old,
      first visit, major physical or psychological disease at time of visit and
      advanced neoplasia. MAIN MEASUREMENTS: Patients received written information on
      the DWA along with the self-administered questionnaire that consisted of five
      closed questions and free comment. RESULTS: 107 questionnaires were received back
      (81%). 57.6% were women; and mean age was 55 (40-87). 97% thought the DWA was
      interesting. 39.3% said they would formalise a DWA and a further 39.3% thought it
      possible they would. If they did so, 88.8% wanted to discuss it with family
      members and 73.8% with their family doctor. 32.1% had already talked "clearly"
      with their family members about terminal care, and 31.1% had talked "in general
      terms". 36.8% said they had not talked about it. 86% found it "not at all
      uncomfortable" to read the document. 38 respondents wrote comments about a
      dignified death, freedom to decide, the relevance of the DWA, the importance of
      being informed and euthanasia. CONCLUSIONS: Participants were clearly in favour
      of the DWA and many fully intended to formalise it. They wanted to discuss the
      question with family members and their doctors. Thinking about it did not make
      them uncomfortable. The recent legalisation of the DWA may help patients and
      doctors to talk openly about care at the end of life.

PMID- 12812689
TI  - [Group versus individual education for type-2 diabetes patients].
AB  - OBJECTIVES: To compare the effectiveness of group (GE) and individual (IE) health
      education in type-2 diabetes patients, and identify the improvement in knowledge,
      metabolic control and risk factors. DESIGN: Randomised clinical trial. SETTING:
      Primary care.Participants. 68 patients with type-2 diabetes, diagnosed 6 months
      before the start of the study and who had not received GE. Patients aged over 75,
      those with sensory, psychological and/or physical deficiencies and those not
      monitored in primary care were excluded (alpha=0.05; beta=0.2).Interventions.
      Patients were selected according to the inclusion criteria and allocated at
      random to the IE (n=33) or GE (n=35) group. Individual and group lessons were
      given at the same time for a year. The contents were evaluated with a validated,
      self-administered test. MAIN MEASUREMENTS: General, demographic variables,
      analyses, blood pressure, the Body Mass Index (BMI), the presence of
      cardiovascular risk factors, diabetes-related complications and therapeutic
      variables were all measured. RESULTS: The two kinds of education showed no
      significant differences from each other. The two groups improved the level of
      knowledge (P<0.001), and reduced HbA1c (P<0.001), HDL-C (P<0.001), the BMI
      (P=0.001) and systolic pressure (P=0.004), and increased their use of reactive
      strips (P=0.02). CONCLUSIONS: Health education on diabetes improved knowledge of
      the disease, metabolic control and cardiovascular risk factors. The two
      educational methods evaluated were equally effective.

PMID- 12812690
TI  - [Reflections on the use of antibiotics in primary care].

PMID- 12812691
TI  - [Tutoring family medicine research in Mexico].

PMID- 12812692
TI  - [Updating of prevention of gastro-duodenal ulcers caused by NSAIDs and their
      complications].

PMID- 12812693
TI  - [Raynaud's phenomenon and sclerodermia].

PMID- 12812694
TI  - [Illness due to iron deposit in a 38-year old man].

PMID- 12812695
TI  - [The Ramadan fast and an emergency unit].

PMID- 12812696
TI  - [Diagnosis of sub-clinical hypothyroidism in primary care and referral to
      specialist care].

PMID- 12812697
TI  - [Use of antibiotics for chronic pharyngitis?].

PMID- 12812698
TI  - [Colorectal cancer screening in primary care?].

PMID- 12812699
TI  - [Rhabdomyolysis in neuroleptics: are we talking of neuroleptic malignant
      syndrome?].

PMID- 12812700
TI  - [How well do our patients accept medical prescriptions not financed by the
      National Health system?].

PMID- 12812701
TI  - [Thiopurine methyltransferase activity and myelosuppression in inflammatory bowel
      disease patients treated with azathioprine and 6-mercaptopurine].
AB  - BACKGROUND AND OBJECTIVE: We aimed at assessing whether there exists a
      relationship between thiopurine methyltransferase (TPMT) activity and the
      incidence of adverse events, especially myelotoxicity, in patients with
      inflammatory bowel disease treated with azathioprine (AZA) or 6-mercaptopurine (6
      MP). PATIENTS AND METHOD: By means of a radiochemical method, we determined the
      TPMT activity in erythrocytes of patients with inflammatory bowel disease who had
      received previously or at the time of the study AZA or 6-MP (n = 97). A group of
      37 patients who had never been treated with these drugs was included. We studied
      the relationship between several variables and TPMT values as well as their
      correlation with adverse events. RESULTS: Mean (SD) TPMT value was 20.8 (5) U/ml
      erythrocytes (from 7.8 to 32.7). There was no patient with low TPMT levels (< 5);
      9% patients had intermediate levels (from 5 to 13.7 U/ml), while 91% displayed
      high levels (>= 13.8 U/ml). There were no differences when comparing TPMT values
      according to several variables such as age, gender, tobacco consumption, weight,
      type of inflammatory bowel disease, and treatment with 5-aminosalicylates,
      steroids or AZA/6-MP. Side effects were seen in 13 out of 97 (13%) patients
      administered AZA/6-MP. None patient with side effects exhibited low TPMT levels
      (< 5 U/ml), nor even intermediate levels (5-13.7 U/ml). There were no differences
      when comparing mean TPMT values in patients with side effects and in those
      without side effects. CONCLUSIONS: In this study, the usefulness of the
      determination of the TPMT activity to identify patients with inflammatory bowel
      disease at risk of myelotoxicity due to AZA or 6-MP has not been confirmed.
      Therefore, even when the TPMT enzymatic activity is normal, it is necessary to
      continue performing the periodic laboratory analysis.

PMID- 12812702
TI  - [Seasonal variation in plasma fibrinogen in dipper and non-dipper patients with
      mild-moderate essential hypertension].
AB  - BACKGROUND AND OBJECTIVE: Increased plasma fibrinogen is recognized as a
      significant parameter for assessing the potential risk of myocardial infarction
      and stroke. A seasonal variation has been reported for plasma fibrinogen, with
      highest values occurring in the coldest months of the year. On the other hand,
      the lack of nocturnal decline in blood pressure has been associated with an
      increase in cardiovascular events. Accordingly, we have quantified the yearly
      variation in plasma fibrinogen in hypertensive patients classified according to
      their nocturnal decline in blood pressure. PATIENTS AND METHOD: We studied 577
      mild-to-moderate hypertensive patients (254 men), 53.8 13.8 years of age. Blood
      pressure was measured every 20 min during the day and every 30 min at night for
      48 consecutive hours. Physical activity was simultaneously evaluated at 1-min
      intervals with a wrist actigraph. A complete blood test was performed on the same
      day before starting blood pressure monitoring. The circannual variation of plasma
      fibrinogen was established for all patients as well as for subgroups of dippers
      (n = 287) and non-dippers (n = 290; patients with a nocturnal blood pressure
      decline < 10% of the diurnal mean) by multiple-component analysis. RESULTS: For
      the whole group of hypertensive patients, plasma fibrinogen was characterized by
      a highly significant seasonal variation (p < 0.001), with a mean value of 324
      mg/dl, double circannual amplitude (i.e, extent of predictable change along the
      year) of 75 mg/dl, and time of peak value on the first week of March. This
      circannual variation can be best represented by a model that includes components
      with periods of 12 and 6 months. The same model also characterized dippers as
      well as non-dippers, analyzed separately. Non-dippers showed higher plasma
      fibrinogen throughout the whole year as compared to dippers (p = 0.002).
      CONCLUSIONS: The elevation of plasma fibrinogen in non-dipper patients as
      compared to dippers could support the association between the lack of nocturnal
      decline in blood pressure with an increase in cardiovascular events, since the
      circannual variation in fibrinogen is timely correlated with the reported yearly
      variation in coronary events.

PMID- 12812703
TI  - [Relationship between clinical and therapeutic variables and health-related
      quality of life in patients with hypertension. MINICHAL Study].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to evaluate, through the health
      related quality of life (HRQoL) questionnaire MINICHAL, the influence of socio
      demographic, clinical and therapeutic variables on health related quality of life
      of hypertensive patients. PATIENTS AND METHOD: An observational, prospective and
      multi-center study was carried out in hypertensive patients who were either
      starting or undergoing a modification of antihypertensive treatment. A total of
      three visits was done: a baseline visit and two follow-up visits at one and six
      months. At all three visits, several socio-demographic, clinical and therapeutic
      variables were recorded and HRQoL was measured using the MINICHAL questionnaire,
      the Spanish version of the Psychological General Well-Being Index, and a single
      question about the change in general health status. The objective was to evaluate
      the impact of these variables on HRQoL. RESULTS: 736 patients with hypertension
      were evaluated. In the multivariate analysis, gender, number of concomitant
      diseases, degree of hypertension, organ damage and educational level were all
      variables displaying a relation with HRQoL. After 6 months of treatment
      intensification, an improvement of HRQoL was observed. Moreover, a positive
      correlation was observed between the degree of reduction of blood pressure (BP)
      and heart rate and HRQoL improvement, especially in the State of mind dimension.
      CONCLUSIONS: In hypertension, a better BP control has a positive influence on
      HRQoL. As several clinical variables are negatively correlated with HRQoL,
      specific interventions are needed to correct modifiable factors.

PMID- 12812704
TI  - [Emergencies in patients attender in a drug abuse treatment center].
AB  - BACKGROUND AND OBJECTIVE: To find out the type of emergency consultations made by
      users at a substance abuse treatment center (SATC). PATIENTS AND METHOD:
      Prospective study of emergency consultations made during six months by patients
      controlled at a SATC. RESULTS: 333 patients were followed up; 27 (8%) of them
      consulted and 9 (33%) were found to have an HIV infection. Heroin addicts
      consulted more times and repeated visits more commonly than cocaine addicts (p <
      0.04 and 0.03). Patients enrolled in the methadone maintenance programme
      consulted less commonly than patients included in other programmes (p < 0.01).
      35% of visited patients did not need treatment and 75% were discharged.
      CONCLUSIONS: We have detected two different types of consultations: those owing
      to a psychiatric/drug disorder in patients followed-up for less than 1 year,
      which are resolved after just one visit, without need of hospitalization; and
      those consultations caused by medical disorders, frequently related to HIV, which
      are generated by patients submitted to longer follow-up periods; these patients
      use to repeat the consultations and are commonly admitted.

PMID- 12812705
TI  - [Hypertension and primary health-care: Impact of new studies].

PMID- 12812706
TI  - [Nutritional rickets in childhood: analysis of 62 cases].
AB  - BACKGROUND AND OBJECTIVE: Until recently, rickets secondary to vitamin D
      deficiency was considered a medical oddity rather than a clinical reality in
      Catalonia (Spain). However, recent data show a reemergence of the disease in the
      infancy. PATIENTS AND METHOD: Retrospective clinical survey of epidemiologic and
      clinical features of infants and children (34 boys and 28 girls) diagnosed of
      nutritional rickets in pediatric departments of Catalonia (Spain) over the last
      10 years. RESULTS: Mean age (SD) at diagnosis was 9.9 (7) months (range: 3-36),
      35.5% were under 6 months. Race distribution: blacks 61.3%, dark-skinned 36%;
      white 6.4%. Country of origin: Sub-Saharan Africa 59.7%, Morocco 33.9%, Catalonia
      3.2%, Pakistan 1.6%. Seasonal distribution: 60% were diagnosed in autumn and
      winter. At diagnosis, 72% were following an exclusive milk diet (48% maternal
      milk alone) without vitamin D supplementation. Most common clinical presentation
      in infants under 6 months was: hypocalcemic tetany/seizures; in children aged 6
      12 months: failure to thrive; and in children over 12 months: skeletal
      deformities. Weight and height expressed as z-score value at diagnosis was 0.67
      and 0.91, respectively. CONCLUSIONS: Nutritional rickets is a current reality in
      Catalonia and it mainly affects immigrant infants and children from Sub-Saharan
      Africa and Morocco, black or dark-skinned, fed with maternal milk alone, without
      vitamin D supplementation and with little sun exposure. Systematic, preventive
      supplementation with vitamin D is essential in these populations.

PMID- 12812707
TI  - [Fish omega-3 fatty acids and risk of coronary heart disease].
AB  - A great amount of evidence from epidemiological studies and clinical trials
      supports a protective effect against coronary heart disease for fish consumption
      and intake of marine omega-3 fatty acids. Biological pathways for this risk
      reduction include membrane stabilization in the cardiac myocite, inhibition of
      platelet aggregation, favourable modifications of the lipid profile, decrease in
      blood pressure and reduction of the inflammatory response of the endothelium.
      Results from epidemiological studies suggest a threshold effect for the
      consumption of fish and omega-3 fatty acids. Risk reduction is especially
      important for cardiac sudden death. Nevertheless, protection against non-fatal
      coronary heart disease has also been observed. Recently published studies have
      shown that mercury intake, present in high concentrations in fish, could
      counteract the beneficial effect from fish consumption.

PMID- 12812708
TI  - [Treatment of community-acquired pneumonia].

PMID- 12812709
TI  - [Disseminated Penicillium marneffei infection in a HIV-infected patient].

PMID- 12812710
TI  - [Hepatitis B immunization and hematopoietic stem cell transplantation].

PMID- 12812711
TI  - [Drug Design].

PMID- 12812712
TI  - [Rabbit syndrome due to clebopride].

PMID- 12812713
TI  - [Reversible brain involvement in multicentric Castlemans disease].

PMID- 12812714
TI  - Relationship between whole-blood interferon-gamma production and extent of
      radiographic disease in patients with pulmonary tuberculosis.
AB  - The aim of this study was to determine whether whole-blood interferon-gamma (IFN
      gamma) production correlates with the radiographic extent of pulmonary
      tuberculosis before treatment. The subjects were 40 human immunodeficiency virus
      negative patients with pulmonary tuberculosis and 36 healthy volunteers. The
      concentrations of IFN-gamma in whole blood stimulated with Mycobactrium
      tuberculosis purified protein derivatives (tuberculous PPD) and
      phytohemagglutinin (PHA) were evaluated. PHA-stimulated IFN-gamma (PHA-IFN-gamma)
      was lower in the patients than in healthy volunteers (p < 0.05), and inversely
      correlated with the disease extent (p < 0.01). Tuberculous PPD-stimulated IFN
      gamma as a percentage of PHA response (tuberculous PPD-IFN-gamma/PHA-IFN-gamma)
      was higher in the patients than in healthy volunteers (p < 0.05). However,
      tuberculous PPD-IFN-gamma/PHA-IFN-gamma did not correlate with the disease
      extent. Our results indicate that the tuberculous PPD-IFN-gamma/PHA-IFN-gamma may
      be useful for the diagnosis of tuberculosis but not for evaluating the disease
      severity, and suggest that PHA-IFN-gamma could be considered as a marker of
      disease severity.

PMID- 12812715
TI  - Diagnostic genotyping of Old and New World Leishmania species by PCR-RFLP.
AB  - We have designed a new genotyping scheme for molecular diagnosis of the different
      Leishmania species pathogenic to humans. This scheme is based on PCR amplified
      sequences from the gene for the spliced leader RNA (mini-exon). This target was
      selected because it is present as tandem repeats (100 to 200 copies) in the genus
      Leishmania and other kinetoplastida, but is absent from the mammalian hosts and
      the sandfly vectors. The exon is highly conserved, whereas the intron and non
      transcribed spacer region vary in size and sequence among different species.
      Thus, it was possible to amplify DNA from both Old and New World pathogenic
      Leishmania complexes using a single pair of primers deriving from the conserved
      region of the mini-exon tandem repeat. Species identification was performed by
      digesting mini-exon PCR products with one or two different restriction enzymes.
      Restriction fragment length polymorphism (RFLP) generated species-specific
      patterns of bands visualized in agarose gels, which allowed to differentiate each
      species unequivocally.

PMID- 12812716
TI  - Evaluation of MicroScan ESBL confirmation panel for Enterobacteriaceae-producing,
      extended-spectrum beta-lactamases isolated in Japan.
AB  - We assessed use of the MicroScan ESBL confirmation panel (Dade Behring, Tokyo,
      Japan) for the detection of eight Enterobacteriaceae-producing extended-spectrum
      beta-lactamases (ESBL) species. Of 137 bacterial strains isolated from patients
      in 32 hospitals in the Kinki area of Japan, 91 produced ESBL and comprised 60
      bacteria (of E. coli, K. oxytoca, and K. pneumoniae) targeted by the NCCLS ESBL
      test and 31 non-target bacteria such as chromosomal AmpC-producing bacteria
      (e.g., Serratia marcescens, Enterobacter spp.). Sensitivity and specificity of
      the MicroScan panel for the target bacteria were 92% and 93%, respectively;
      sensitivity and specificity for non-target bacteria were 52% and 100%,
      respectively. There were 20 ESBL-positive strains that were not inhibited by
      clavulanic acid in the MicroScan panel (3 of 32 ESBL-producing E. coli strains, 1
      of 24 K. pneumoniae, 1 of 4 K. oxytoca, 8 of 13 E. cloacae, and 7 of 14 S.
      marcescens), and most of them were bacteria not targeted by the NCCLS test. In 19
      of the 20 strains, the synergy effect of clavulanic acid was observed in the
      modified-double-disk synergy test using only the cefepime-disk. Because these
      strains had high MICs of > or = 16 microg/ml for cephamycins such as cefoxitin
      and cefmetazole, these strains might produce high levels of AmpC in addition to
      ESBL. The MicroScan ESBL confirmation panel showed excellent performance in
      detecting target, but not other bacteria. Addition of cefepime and clavulanic
      acid to the MicroScan panel may significantly improve detection of non-target
      bacteria.

PMID- 12812717
TI  - In vitro evaluation of the activity of two doses of Levofloxacin alone and in
      combination with other agents against Pseudomonas aeruginosa.
AB  - P. aeruginosa is one of the most difficult to treat pathogens that generally
      requires combination therapy to prevent the development of resistance. This study
      evaluated the in vitro activity of two concentrations of levofloxacin (modeled
      for the 500 mg and 750 mg daily dose) in combination with ceftazidime, cefepime,
      piperacillin/tazobactam, imipenem, and tobramycin against P. aeruginosa. MICs and
      time-kill studies were performed against 12 non-duplicate clinical isolates of P.
      aeruginosa. The percent susceptible for levofloxacin, ceftazidime, cefepime,
      piperacillin/tazobactam, imipenem, and tobramycin were 67%, 58%, 58%, 67%, 75%,
      and 100%, respectively. Tobramycin was the most active single agent, killing and
      maintaining > or =99.9% killing over a 24 h period against all isolates.
      Levofloxacin 4 microg/mL(750 mg/day) alone reached 99.9% killing and maintain
      this killing over the time period more often than levofloxacin 2 microg/mL (500
      mg/day). No combination was antagonistic and all combinations with tobramycin
      were indifferent. Overall, levofloxacin 2 microg/mL plus a beta-lactam was
      synergistic (65%) more often than levofloxacin 4 microg/mL combinations (46%).
      This was not unexpected due to the increased activity of levofloxacin 4
      microg/mL. However, levofloxacin 4 microg/mL combinations maintained a > or
      =99.9% killing over the entire 24 h period more often than levofloxacin 2
      microg/mL combinations (94% vs 83%). The findings from this work suggest that
      levofloxacin 750 mg/day in combination with another agent active against P.
      aeruginosa may prove to be clinically beneficial and superior to combinations
      using lower doses of levofloxacin. In vivo studies are needed to evaluate the
      clinical significance of these findings.

PMID- 12812718
TI  - Detection of mutations in quinolone resistance-determining regions in
      levofloxacin- and methicillin-resistant Staphylococcus aureus: effects of the
      mutations on fluoroquinolone MICs.
AB  - The minimum inhibitory concentrations (MICs) of 18 antibiotics were determined
      for 66 clinical isolates of staphylococci. Genotypes, mutations in the quinolone
      resistance-determining regions (QRDRs), and effect of efflux were determined in
      the 18 levofloxacin-resistant isolates, for which the MICs of levofloxacin were
      high (> or =8 microg/ml). The increased levofloxacin resistance mainly resulted
      from some combinations of mutations in the QRDRs, although NorA-mediated efflux
      may play a minor role in resistance. A combination of mutations in GrlA
      (Ser80Phe), GrlB (Pro451Ser), and GyrA (Ser84Leu) was found in 4 methicillin
      resistant Staphylococcus aureus (MRSA) isolates that were unrelated
      genotypically. The mutations in grlA QRDR varied in the isolates classified as
      being in an identical pulsed-field gel electrophoresis (PFGE) group, although the
      grlB, gyrA, and gyrB QRDRs were the same. These results suggest that the patterns
      of amino acid mutations in the QRDRs can provide distinct epidemiologic
      information from PFGE genotypes in fluoroquinolone-resistant MRSA. A combination
      of at least three mutations in GrlA, GrlB, and/or GyrA is required to increase
      the MICs of fluoroquinolones, although all of the levofloxacin-resistant MRSA
      retained the MICs of sitafloxacin in the range of 1 to 2 microg/ml.

PMID- 12812720
TI  - Use of INNO-LIPA assay for rapid identification of mycobacteria.
AB  - Using 106 clinical isolates of mycobacteria, we showed that INNO-LIPA
      Mycobacteria assay is an excellent tool to rapidly identify the most frequently
      isolated nontuberculous mycobacteria, in one procedure. It may be used as an
      additional technique to AccuProbe assay, which remains the fastest and the
      cheapest tool for a rapid and accurate identification of the M. tuberculosis
      complex.

PMID- 12812719
TI  - Re-evaluation of quality control guidelines for gatifloxacin and garenoxacin
      (BMS284756) when susceptibility testing Haemophilus influenzae and Streptococcus
      pneumoniae.
AB  - An eight laboratory M23-A2 quality control (QC) study was performed for the re
      evaluation of gatifloxacin, a new fluoroquinolone, using disk diffusion tests
      against Streptococcus pneumoniae ATCC 49619. The study also re-evaluated
      garenoxacin, a novel investigational des-F(6)-quinolone, using disk diffusion
      tests against S. pneumoniae ATCC 49619 and broth MIC for Hemophilus influenzae
      ATCC 49247. The gatifloxacin zone diameter results for S. pneumoniae did not
      indicate a need for QC range modification (26-34 mm; 98.3% of results); however,
      the garenoxacin zone diameters did demonstrate a need for a minor modification (1
      mm; 26-34 mm; 96.3% of reported results). The broth MIC results for H. influenzae
      showed that 83.1% of the results were at the upper limit of the current range
      (0.008 microg/ml) published by the National Committee for Clinical Laboratory
      Standards (NCCLS). The proposed correction could either be 0.002-0.015
      microg/mlor 0.004-0.015 microg/ml, each encompassing 100.0% of reported results
      (prior and current studies). All MIC results for control drugs, levofloxacin and
      moxifloxacin (disks) or gatifloxacin and clarithromycin (MIC), were within
      published NCCLS ranges.

PMID- 12812721
TI  - Detection of intrinsic vancomycin resistant enterococci in animal and human
      feces.
AB  - Fecal samples from animal species and humans were analyzed by quantitative
      culture for enterococci and vancomycin resistant enterococci (VRE). Each host
      species carried enterococci which exhibited intrinsic intermediate resistance to
      vancomycin and sensitivity to teicoplanin (Van C phenotype). The carriage rate in
      humans was 9%. Carriage rates varied among animal species with the highest
      percentages being found in deer, duck, goose, horse and turkey.

PMID- 12812722
TI  - Analysis of the vacA, cagA, cagE, iceA, and babA2 genes in Helicobacter pylori
      from sixty-one pediatric patients from the Midwestern United States.
AB  - This study was designed to characterize H. pylori from pediatric gastric biopsy
      specimens in terms of several genes (vacA, cagA, cagE, iceA1, iceA2, and babA2)
      proposed to be involved in the pathogenesis of this organism. Many of these genes
      have been studied in adult H. pylori isolates, however, these genes have not been
      well characterized in H. pylori from children. Using PCR we observed that 44% of
      the H. pylori in our biopsies shared two common genotypes (vacA s1b m1, cagA,
      cagE, iceA2 +/- babA2). While 26% of the H. pylori had unique genotypes. The cag
      pathogenicity island associated genes, cagA and cagE, were found together in 64%
      or our H. pylori, while 84% were iceA2 positive. The presence of the babA2 gene
      has been proposed to be associated with a higher risk of H. pylori related
      diseases, however, we found that only 36% of our H. pylori contained this gene.

PMID- 12812723
TI  - Specific oligonucleotide primers for identification of Hortaea werneckii, a
      causative agent of tinea nigra.
AB  - Hortaea werneckii, a black yeast-like hyphomycete that is widely distributed in
      tropical and subtropical environments, can cause superficial mycotic infection in
      humans. This fungus was recently isolated from superficial infectious lesions of
      a guinea pig in Japan. An oligonucleotide primer set specific for Hortaea
      werneckii was designed on the basis of the internal transcribed spacer regions of
      the ribosomal DNA (rDNA). Polymerase chain reaction (PCR) with this primer set
      yielded a 306 bp PCR amplicon from only H. werneckii. This primer set did not
      amplify DNAs of 42 other related dematiaceous species, including the medically
      important dematiaceous fungi Cladophialophora carrionii, Fonsecaea pedrosoi,
      Phialophora verrucosa, and Exophiala dermatitidis, and eight species of medically
      important yeasts, including Candida (C.) albicans, C. dublinensis, C. glabrata,
      C. parapsilosis, C. tropicalis, Cryptococcus neoformans var. neoformans,
      Malassezia furfur, and Trichosporon asahii var. asahii. PCR with this primer set
      may be a useful technique for rapid identification of H. werneckii.

PMID- 12812724
TI  - Early diagnosis of Exophiala CAPD peritonitis by 18S ribosomal RNA gene
      sequencing and its clinical significance.
AB  - Phenotypic identification of fungi in clinical microbiology laboratories is often
      difficult and late, especially for slow growing and rarely encountered fungi. We
      describe the application of 18S ribosomal RNA (rRNA) gene sequencing in the early
      diagnosis of a case of Exophiala peritonitis. A yeast-like fungus was isolated
      from the dialysate fluid of a 66-year-old man undergoing continuous ambulatory
      peritoneal dialysis. It grew slowly after 12 days of incubation to yield mature
      cultures to permit recognition of microscopic features resembling those of
      Exophiala, a dematiacerous mold. 18S rRNA gene sequencing provided results 12
      days earlier than phenotypic identification and revealed 15 base difference
      (0.9%) between the isolate and Exophiala sp. strain GHP 1205 (GenBank Accession
      no. AJ232954), indicating that the isolate most closely resembles a strain of
      Exophiala species. The patient responded to 4 weeks of intravenous amphotericin B
      therapy. Early identification of the fungus was important for the choice of anti
      fungal regimen. As opportunistic fungal infections in immunocompromised patients
      are globally emerging problems, the development of molecular techniques for
      fungal identification is crucial for early diagnosis and appropriate treatment.

PMID- 12812725
TI  - Detecting environmental change: science and society-perspectives on long-term
      research and monitoring in the 21st century.
AB  - Widespread concern over the state of the environment and the impacts of
      anthropogenic activities on ecosystem services and functions has highlighted the
      need for high-quality, long-term datasets for detecting and understanding
      environmental change. In July 2001, an international conference reviewed progress
      in the field of long-term ecosystem research and monitoring (LTERM). Examples are
      given which demonstrate the need for long-term environmental monitoring and
      research, for palaeoecological reconstructions of past environments and for
      applied use of historical records that inform us of past environmental
      conditions. LTERM approaches are needed to provide measures of baseline
      conditions and for informing decisions on ecosystem management and environmental
      policy formulation. They are also valuable in aiding the understanding of the
      processes of environmental change, including the integrated effects of natural
      and anthropogenic drivers and pressures, recovery from stress and resilience of
      species, populations, communities and ecosystems. The authors argue that, in
      order to realise the full potential of LTERM approaches, progress must be made in
      four key areas: (i) increase the number, variety and scope of LTERM activities to
      help define the operational range of ecosystems; (ii) greater integration of
      research, monitoring, modelling, palaeoecological reconstruction and remote
      sensing to create a broad-scale early warning system of environmental change;
      (iii) development of inter-disciplinary approaches which draw upon social and
      environmental science expertise to understand the factors determining the
      vulnerability and resilience of the nature-society system to change; and (iv)
      more and better use of LTERM data and information to inform the public and
      policymakers and to provide guidance on sustainable development.

PMID- 12812726
TI  - Monitoring change in hydrological systems.
AB  - Monitoring is the process by which we keep the behaviour of the environment in
      view, providing essential information on how systems are changing and how fast,
      and allows us to learn to adjust what we are doing to get the best out of the
      system. This paper reviews the ways in which long-term study of the natural
      environment can be achieved. Three hydrological examples are then presented:
      nitrate leaching in a small agricultural catchment in south west England; the
      impact of drought on the peat-covered headwaters of the River Tees in northern
      England; and the impact of clear-felling on forest hydrology and nutrient export
      in the southern Appalachians. Monitoring programmes, if well designed and
      properly maintained, can provide important evidence of environmental change,
      revealing unexpected patterns and stimulating experimental research. The
      existence of long, reliable data sets considerably increases our ability to make
      informed decisions about the way in which we manage our river catchments.

PMID- 12812727
TI  - Environmental change in river channels: a neglected element. Towards
      geomorphological typologies, standards and monitoring.
AB  - Rivers integrate the impacts of change in atmospheric and terrestrial systems;
      they then deliver these to the coast. En route geomorphological processes create
      dynamic and diverse habitats, both in-stream and in riparian/floodplain ecotones.
      The dynamics of channel change conflict with human resource development, the
      outcome is that many river and riparian environments have been significantly
      modified, complicating the interpretation of change. Collection of
      geomorphological data on both form and process has to date been overwhelmingly an
      academic pursuit; standard measurement networks and long-term monitoring have, as
      a result been largely absent-as in the Environmental Change Network (ECN),
      despite the emerging requirements of legislation such as the EU Water Framework
      Directive. In this paper, we utilise a unique set of repeat channel surveys and
      long-term bed-load sediment yields to provide guidance on both definitions of
      change and those variables and survey techniques which might form the basis, in
      future, of improved national-scale monitoring. The Environment Agency's River
      Habitat Surveys suggest the basis for channel typologies that could structure a
      sampling framework and rationalise the variables to be monitored. We also point
      to the value of more detailed geomorphological procedures in use at the
      catchment/project scale-Catchment Baseline Surveys and Fluvial Audits-as a
      standardised basis for monitoring the detail of change in the fluvial sediment
      system. A perfect opportunity to lay foundations for such monitoring activity has
      been provided in England and Wales by the winter floods of 2000/2001.

PMID- 12812728
TI  - The natural (baseline) quality of groundwater: a UK pilot study.
AB  - Knowledge of the natural baseline quality of groundwaters is an essential
      prerequisite for understanding pollution and for imposing regulatory limits. The
      natural baseline of groundwaters may show a range of concentrations depending on
      aquifer mineralogy, facies changes, flow paths and residence time. The
      geochemical controls on natural concentrations are discussed and an approach to
      defining baseline concentrations using geochemical and statistical tools is
      proposed. The approach is illustrated using a flowline from the Chalk aquifer in
      Berkshire, UK where aerobic and anaerobic sections of the aquifer are separately
      considered. The baseline concentrations for some elements are close to
      atmospheric values whereas others evolve through time-dependent water-rock
      interaction. Certain solutes (K, NH(4)(+)), often considered contaminants, reach
      naturally high concentrations due to geochemical controls; transition metal
      concentrations are generally low, although their concentrations may be modified
      by redox controls. It is recommended that the baseline approach be incorporated
      into future management strategies, notably monitoring.

PMID- 12812729
TI  - Lakes in the Finnish Eurowaternet: status and trends.
AB  - The Eurowaternet is a monitoring network designed to cover all European
      countries, with the overall objective of obtaining timely, quantitative and
      comparative information on the status of inland waters so that their key
      environmental problems can be defined, quantified and monitored. Finland launched
      the Eurowaternet for lakes in 2000. The network was set up according to
      guidelines of the European Environment Agency (EEA) and was based on national,
      regional and local monitoring programmes. It includes 253 lake sites, divided
      into the following groups by, for example, their loading background and size: (i)
      reference sites, (ii) point-source loading (impact) sites, (iii) agricultural
      sites, (iv) representative sites, i.e. lakes <100 km(2) with typical water
      quality in the catchment and (v) lake deep sites in large lakes (>100 km(2)). We
      examined the water quality and its development during 1976-2001 in these groups,
      using data from surface and near-bottom water layers at summer and winter
      stagnation. In addition, the representativeness of the network was evaluated.
      Summer mean concentrations of total P (TP) during 1990-2001 in surface water were
      (i) 6.8+/-1.8 microg 1(-1) in reference lakes, (ii) 24+/-5 microg 1(-1) in lakes
      affected by point loading, (iii) 58+/-32 microg l(-1) in agricultural lakes, (iv)
      14+/-2.2 microg l(-1) in representative lakes and (v) 11+/-2.1 microg l(-1) in
      large lakes. Comparison with reference lakes revealed major impact of human
      activities on TP and total N (TN)-and consequently on chlorophyll a (a-chl) and
      transparency-in all other groups, especially agricultural lakes. Decreasing TP
      and increasing O(2) trends were found at impact sites, reflecting water
      protection measures taken in pulp and paper mills and municipalities. More
      surprisingly, we found increasing alkalinity trends in all but agricultural sites
      and decreasing NO(2)-N+NO(3)-N (NO(x)-N) trends particularly in pelagic areas of
      large lakes. Comparison of water quality in Eurowaternet lakes with those in
      randomly sampled lakes (Finnish Lake Survey) revealed that the Eurowaternet
      covers the entire range of concentrations of TP, TN and conductivity in Finnish
      lakes, but <1-km(2), eutrophic and/or brown water lakes are underrepresented.
      Only 0.2% of a total of 13114 small lakes (0.1-1 km(2)) are included in the
      annual monitoring program of the Eurowaternet.

PMID- 12812730
TI  - Trends of phosphorus, nitrogen and chlorophyll a concentrations in Finnish rivers
      and lakes in 1975-2000.
AB  - During recent decades the amounts of nutrients discharged to Finnish surface
      waters have markedly decreased. This has been achieved by considerable
      investments in water protection, which were made mainly to improve municipal and
      industrial wastewater purification. We investigated whether these water
      protection measures have decreased phosphorus and nitrogen concentrations in
      Finnish rivers and lakes. In addition, possible trends in chlorophyll a
      concentrations in lakes were studied. The data consisted of a total of over 68000
      monitoring results of 22 rivers and 173 lakes (or sub-basins of lakes) with
      different types of catchment areas. The study period covered the years 1975-2000
      and the non-parametric Kendall Tau b and Seasonal Kendall tests were applied for
      detecting trends. Decreasing nutrient concentration trends were typical in many
      lakes and rivers earlier polluted by municipal and industrial wastewaters.
      Increasing nutrient concentration trends were common in smaller rivers and lakes
      receiving diffuse loading from agriculture. The results show that the investments
      directed towards wastewater purification have effectively improved the quality of
      Finnish inland waters. However, no clear effects of decreasing non-point loading
      were found. Thus, more effective measures should be directed towards decreasing
      non-point source loading.

PMID- 12812731
TI  - Explaining lake and catchment change using sediment derived and written
      histories: an Australian perspective.
AB  - Palaeolimnological records can be powerfully combined with documentary data to
      explain the impact of modern industry and agriculture on lake systems and their
      catchments. Such an approach is highly appropriate in Australia since modern
      society was imposed on a continent until recently populated solely by hunter
      gatherers and because there is a wealth of historical data to draw upon.
      Confounding factors such as the influence of climate change, depopulation of the
      indigenous community and non-linear responses to human impact must be considered
      in analysis of the relative importance of various land use changes upon lake
      pollution.

PMID- 12812732
TI  - Long-term studies (1871-2000) on acidification and recovery of lakes in the
      Bohemian Forest (central Europe).
AB  - This paper evaluates long-term changes in the atmospheric depositions of S and N
      compounds, lake water quality, and biodiversity at eight glacial lakes in the
      Bohemian Forest over the past 130 years. This time interval covers (i) the
      'background' pre-acidification status of the lakes, (ii) a period of changes in
      the communities that can be partly explained by introduction of fish, (iii) a
      period of strong lake acidification with its adverse impacts on the communities,
      (iv) the lake reversal from acidity, which includes the recent status of the
      lakes. The lake water chemistry has followed-with a characteristic hysteresis
      both the sharp increase and decline in the deposition trends of strong anions.
      Remarkable changes in biota have mirrored the changing water quality. Fish became
      extinct and most species of zooplankton (Crustacea) and benthos (Ephemeroptera
      and Plecoptera) retreated due to the lake water acidification. Independent of
      ongoing chemical reversal, microorganisms remain dominant in the recent plankton
      biomass as well as in controlling the pelagic food webs. The first signs of the
      forthcoming biological recovery have already been evidenced in some lakes, such
      as the population of Ceriodaphnia quadrangula (Cladocera) returning into the
      pelagial of one lake or the increase in both phytoplankton biomass and rotifer
      numbers in another lake.

PMID- 12812733
TI  - Changing perspectives on the importance of urban phosphorus inputs as the cause
      of nutrient enrichment in Lough Neagh.
AB  - The scale and chronology of the phosphorus (P) enrichment of Lough Neagh, a large
      hypertrophic lake, was assessed using, as enrichment proxies, published
      palaeocological studies on diatoms and chironomid head capsules preserved in the
      lake sediments and, from 1974, monitoring data from the lake and its inflowing
      rivers. Enrichment commenced in 1880, and the scale and chronology of the diatom
      and chironomid records were similar up to 1960, but in the 1960s, chironomid
      accumulation rates increased dramatically, whereas diatom rates remained
      unchanged. From subsequent lake monitoring, the absence of a diatom response
      after 1960 was attributed to silica limitation so that P could be considered as
      the driver of increased diatom production only up to 1960. Using a coefficient
      for the demand for P by diatoms of 4 microg P mg SiO(2)(-1), it was calculated
      that the increased diatom production between 1881 and 1961 required an increase
      in lake P of 26 microg P l(-1). This value is close to the predicted increase of
      22.5 microg P l(-1) in the lake caused by inputs of P from sewage treatment works
      and septic tanks. There was no evidence that diffuse source P contributed to
      enrichment over this period. Enrichment up to 1960 appears modest in comparison
      to subsequent years. From 1961 to 1974, lake P was estimated to have increased by
      62 microg P l(-1), but only 25 microg P l(-1) of this increase was attributable
      to greater loadings of P from urban and septic tank sources. The enrichment
      response of chironomids at this time was also much greater than expected from a
      regression-derived relationship between urban P inputs and chironomid
      accumulation rates suggesting additional sources of P. The larger than expected
      increase in lake P was attributed to the onset of a significant internal loading
      of P and the commencement of an increase in diffuse source loadings of P. River
      monitoring has shown that diffuse P has increased steadily since 1974, more than
      counterbalancing a 40% reduction in urban P loadings that has taken place since
      1980. By the end of the 20th century urban sources contributed only 19.7% of
      inflow P to Lough Neagh but lake P was 145 microg P l(-1) compared to an
      estimated concentration of 20 microg P l(-1) in 1881. Failure to control diffuse
      P sources has therefore been instrumental in the continued increase of lake P in
      Lough Neagh.

PMID- 12812734
TI  - Quantifying the effects of forestry practices on the recovery of upland streams
      and lochs from acidification.
AB  - Trends in long-term chemistry data are presented for 37 acidified upland streams
      and lochs, located in four areas (A, B, C and D) across Scotland, to provide a
      comparison between recovery rates of moorland catchments and forest catchments at
      different stages of the management cycle. For all sites, non-marine sulfate (nm
      SO(4)) showed a significant decline in annual median concentrations, the greatest
      decline being in streams draining felled catchments, which showed a 50% greater
      decline than catchments with moorland or young, aggrading forests. A similar
      pattern was found for chloride (Cl) concentrations in Area C, which reflected the
      reduced interception of sea-salt aerosols following clearfelling. However, high
      elevation moorland sites in Area D also revealed significant declines in Cl while
      trends in aggrading forest sites in this area were insignificant. Alkalinity
      (ALK) and pH increased more at sites where felling had taken place than at
      moorland or young forest sites while aggrading forest catchments appeared to be
      most resistant to changes in pH and ALK. Associated with these acid-base changes
      was a corresponding decline in labile aluminium (Al-L) concentrations. The
      pattern of nitrate (NO(3)) change was especially affected by the timing of
      felling in forested catchments. Large negative trends in NO(3) at stream sites
      were associated with felling during the early part of the study period. This
      downward trend was further enhanced as NO(3) concentrations fell below pre
      felling levels as the second rotation crop became established. Few forest sites
      showed significant increases in NO(3) due to felling in the latter part of the
      study period. Most moorland loch sites showed a small but significant increase in
      NO(3,) probably in response to similar increases in N deposition and/or climatic
      impacts. Dissolved organic carbon (DOC) increased significantly at both forest
      and moorland sites, however, the extent of these increasing trends appeared to be
      positively correlated with absolute DOC concentrations. Despite the complex
      response of streams and lochs during the various stages of the forest cycle,
      especially for NO(3), both forest and moorland catchments showed generally
      similar and rapid responses to reductions in S deposition. Nevertheless, forested
      sites are still more acid and have higher concentrations of toxic forms of Al
      than moorland sites. Although the proposed emission reductions in Europe are
      likely to result in a continuing decline in S and N loadings to catchments, the
      continuing policy of planting second rotation forests in these acidified
      catchments may, in the long-term, delay or halt chemical and biological recovery.
      However, in the short-term, any increase in the uptake of N deposition by
      aggrading forests should help to counteract the acidifying effects of a small
      increase in the interception of S and N compounds.

PMID- 12812735
TI  - Time series of long-term annual fluxes in the streamwater of nine forest
      catchments from the Swedish environmental monitoring program (PMK 5).
AB  - International cooperation has contributed to major declines in SO(2) emission and
      S deposition during the last two decades in Europe. The chemical recovery from
      already anthropogenically acidified sites however, has been slow. In the present
      paper, long-term trends of chemical fluxes from nine selected forested reference
      catchments were studied, to detect recovery from acidification and leaching of S
      and base cations (BC). A decline in S deposition resulted in a decreased flux of
      non-marine sulfate (SO(4)*) in seven of nine streams, with statistically
      significant changes in four. The two cases with slight increases in SO(4)* flux
      resulted from increasing water flow. The SO(4)* decrease was followed by a
      recovery from acidification in terms of increased ANC flux in those sites in
      southern Sweden that were chronically acidified. The recovery was probably slowed
      down by leaching of SO(4) from the soil and a decrease in the flux of BC. A
      better understanding of the processes for leaching of SO(4) and BC is needed in
      order to quantify the need for further restrictions of sulfur emissions to allow
      a long term recovery of acidified catchments. The flux calculations available
      from small catchments such as those in this study, are of value for that
      understanding.

PMID- 12812736
TI  - Recovery from acidification of Finnish lakes: regional patterns and relations to
      emission reduction policy.
AB  - The regional-scale response of Finnish headwater lakes to changes in acidifying
      deposition loads was studied using data from a national deposition monitoring
      network (19 stations), acidification monitoring lakes (163 lakes) and results of
      a statistically based national lake survey (873 lakes). Data from 1990 to 1999
      were used for statistical trend analysis. A deposition model was used to assess
      changes in S and N deposition for the year 2010, assuming emission reductions
      according to two international agreements. The deposition of sulfate and H(+)
      showed statistically significant (Kendall-tau, P<0.05) decreasing trends at
      nearly all deposition stations. For N compounds, nearly all slopes were negative,
      but rarely statistically significant. Sulfate concentrations have declined in all
      types of small lakes throughout Finland in the 1990s (significant decline in 64
      85% of the lakes in three different lake regions), indicating a clear response to
      S emission reductions and declined sulfate deposition. Base cation concentrations
      decreased in both deposition and lake water, especially in southern Finland, but
      to a lesser extent than sulfate concentrations. The median slope of the trend for
      Gran alkalinity in lakes ranged between 0.98 and 2.1 microeq l(-1) a(-1). Some
      1400 (27%) of Finnish headwater lakes of size 4-100 ha were estimated to show
      statistically significant increases in Gran alkalinity (recovery). No large
      changes were observed in the lake water TOC concentrations. The reduction in S
      deposition is the main driving factor for the lake acidification recovery process
      in Finland. Deposition model calculations showed that further large reductions in
      S deposition beyond the 1999 level are not likely to occur by the year 2010,
      particularly for southeastern Finland. The mean estimated S deposition change by
      2010 for the three lake regions in Finland was only between -0.9 and -6.6% for
      the two policy scenarios (UN/ECE Gothenburg protocol, EU NEC-directive),
      respectively. A slower acidification recovery of the lake ecosystems is,
      therefore, anticipated in the future.

PMID- 12812738
TI  - The apparent and potential effects of climate change on the inferred
      concentration of dissolved organic matter in a temperate stream (the Malse River,
      South Bohemia).
AB  - Long-term and seasonal changes in concentration of dissolved organic matter (DOM)
      and their possible drivers were evaluated for an upland stream in central Europe
      during 1969-2000. Two periods have been detected within this data set-years with
      decreased DOM until the middle of 1980s and then years with increased DOM until
      2000. Temperature, hydrological regime of runoff from the catchment (namely the
      amount of interflow), and changes in atmospheric deposition of acidity coincided
      with the variations in DOM concentrations. The analysis of single runoff events
      confirmed the relation between the export of increased DOM concentrations from
      the catchment and interflow. A multiple linear regression model based on monthly
      averages of temperature and interflow explained 67% of DOM variability. This
      model suggested a 7% increase in DOM concentration under the scenarios of
      possible future climate change related to doubled CO(2) concentration in the
      atmosphere. The scenarios were based on results of several global circulation
      models.

PMID- 12812737
TI  - Long-term trends in pH, aluminium and dissolved organic carbon in Scottish fresh
      waters; implications for brown trout (Salmo trutta) survival.
AB  - Over the past 30 years upland streams and lochs in Scotland have shown
      significant signs of recovery from acidification, particularly in terms of
      declining concentrations of non-marine sulphate (nm-SO(4)). Long-term index sites
      in central and southwest Scotland reveal a significant decline in the
      concentration of biologically important components, notably acidity (H(+)) and
      labile (toxic) forms of aluminium (Al-L), whilst dissolved organic carbon (DOC)
      and complexed forms of aluminium (AL-NL) have increased significantly. Although
      these improvements should increase the probability of brown trout survival, and
      have resulted in increased acid neutralising capacity (ANC) in fishless streams
      to values close to current critical limits, there is still a relatively poor
      correlation between ANC and current fish status. Site to site variability appears
      to be linked to the relative contribution of (H(+)), Al-L and DOC within the
      critical ANC (ANC(CRIT)) range. It is proposed that ANC(CRIT) should cover a
      range of ANC values as a function of Al-L concentration. Based on field studies
      an empirical range of critical ANC values are suggested which better predict the
      presence of a sustainable brown trout population.

PMID- 12812739
TI  - Modeling and monitoring of long-term acidification in an upland catchment of the
      Western Ore Mountains, SE Germany.
AB  - Modeling and monitoring of acidification patterns in a limed forest catchment in
      the Ore Mountains, SE Germany are presented. A lumped-parameter model, MAGIC,
      satisfactorily reproduced the main parameters of stream water chemistry. Despite
      repeated whole-catchment liming, between 1993 and 1999 stream water pH increased
      from 4.3 to only 4.6, while calcium concentrations declined slightly. Stream
      water sulfate concentration declined from 687 to 396 microeq l(-1), and the
      pronounced effect of deposition decline during the 1990s was probably more
      important than liming.

PMID- 12812740
TI  - Estimating critical load exceedance by combining the EMEP model with data from
      measurement stations.
AB  - We combine EMEP modelled data on acid pollutants with measurements at a network
      of monitoring stations. The aim is to improve the estimation of critical load
      exceedance by accounting for the variability in deposition within an EMEP grid
      square. We also estimate the bias and random error in the EMEP model. We use a
      statistical model which regards both EMEP predictions and measurements as
      observations of an underlying true deposition. By making some reasonable
      assumptions about the form of this underlying truth, and about the errors in the
      EMEP predictions, we can obtain both interesting estimates of the EMEP errors,
      and better estimates of critical load exceedance.

PMID- 12812741
TI  - Design concepts adopted in long-term forest monitoring programs in Europe-
      problems for the future?
AB  - Long-term intensive monitoring in Europe is presently proceeding in more than 800
      plots, where a number of investigations are carried out according to allegedly
      standardized protocols. While the potential of the program cannot be denied,
      certain aspects that are binding for data analysis may be a source of problems
      for future evaluation of program results. Here it is argued that: (i) current
      biological response indicators adopted by the program will not permit air
      pollution effects to be distinguished from effects due to other stressors and/or
      natural variation; (ii) the sampling strategy adopted to select monitoring sites
      does not enable European scale estimates of the status of attributes of interest
      or their changes; and that (iii) the sampling tactic suggested at plot level is
      ambiguous and cannot provide representative, unbiased estimates at plot scale.
      This latter point implies consequences when plot-level data are used in models,
      correlative studies and/or to infer cause-effect relationships.

PMID- 12812742
TI  - Which factors are responsible for the changing lichen floras of London?
AB  - SO(2) is no longer the principal factor influencing the vitality and composition
      of lichen assemblages in London. We provide direct evidence for an impact on
      lichen growth during episodic high exhaust emissions coupled with unusual
      climatic conditions. This suggests a combination of particles and nitrogen plays
      a major role in influencing lichen growth. Nitrogen from traffic emissions may be
      at least as important as agriculture in influencing the composition of lichen
      assemblages.

PMID- 12812743
TI  - The effects of tropospheric ozone and elevated carbon dioxide on potato (Solanum
      tuberosum L. cv. Bintje) growth and yield.
AB  - An open-top chamber experiment with field grown potato (Solanum tuberosum L. cv.
      Bintje) was performed in the south-west of Sweden in 1998. The experiment was
      aimed to investigate individual and interactive impacts of elevated ozone (O(3))
      and carbon dioxide (CO(2)) on potato growth and yield. Treatments were ambient
      and elevated CO(2) with or without the addition of 20 nmol mol(-1) O(3). In
      addition, plants were grown in ambient air plots. Plants grown in elevated CO(2)
      and O(3) had a reduced tuber yield, compared to control, by 2% and 8%,
      respectively. These effects were, however, not statistically significant.
      Elevated CO(2) caused a significantly larger number of tubers of lower average
      size, while elevated O(3) induced significantly lower tuber dry matter content.
      The number of tuber initials (tubers <15 mm) found at harvest was significantly
      lower in elevated O(3). Visible O(3) leaf injury appeared earlier and the number
      of yellow leaves 89 days after emergence was significantly larger in elevated
      O(3). In elevated CO(2), haulm dry weight was significantly (15%) lower at
      harvest and the haulm/tuber ratio was significantly reduced. There were
      significant interactive effects of O(3) and CO(2) on the final number of leaves
      and on stem height. Plants in elevated CO(2) reached final stem height earlier
      than in the other treatments. In summary, it was concluded: (a) that anticipated
      future O(3) levels are likely to have a negative impact on potato growth,
      although tuber yield effects may be hard to demonstrate experimentally in this
      plant due to large variation; (b) that whether any possible beneficial effect of
      elevated CO(2) on the magnitude of tuber yield will be expressed, depend on the
      climatic conditions prevailing; and (c) that potato growth responses to CO(2) and
      O(3) are not simply additive.

PMID- 12812744
TI  - Using environmental and growth characteristics of plants to detect long-term
      changes in response to atmospheric pollution: some examples from British
      beechwoods.
AB  - This study uses the Ellenberg system of plant indicator values, along with Grime
      et al.'s plant growth strategy values, to investigate the nature of temporal
      changes in the composition of ground flora in two beechwoods in the Cotswolds
      region of the UK, currently receiving atmospheric inputs of nitrogen in excess of
      critical loads. The woods, first surveyed in the early 1960s, were resurveyed in
      1998 using the original sampling protocol. Temporal changes in the abundance of
      individual species at Blackstable West Wood indicate changes in light over time,
      although decreases in sun species, and both increases and decreases in shade
      species suggest that this change has been patchy. Analysis of changes in plant
      community as represented by weighted and unweighted quadrat Ellenberg and CSR
      scores have yielded more significant results. Blackstable West Wood shows
      increases in nitrophilic, moist-soil and competitive species accompanied by a
      decline in stress-tolerant species. In Buckholt Top Wood there has been an
      increase in sun and moist-soil species, a decrease in competitive species and,
      when weighted Ellenberg scores are considered, an increase in acid-tolerant
      species. These changes indicate both the impact of woodland management by
      selective felling and an underlying influence of enhanced atmospheric deposition
      especially of nitrogen pollutants. It is concluded that quadrat mean scores are a
      useful tool especially where few individual species have undergone large temporal
      changes in abundance. However, lack of correlations between quadrat Ellenberg
      scores for pH and light on one hand, and their equivalents measured in the field,
      i.e. soil pH and surrogates for light, such as distance to the nearest tree and
      tree density, suggest that this approach may not be sensitive enough to pick up
      small-scale, within site variations. Although harder to interpret, plant strategy
      scores were found to be a useful additional descriptor, encapsulating a plant's
      response to a range of environmental factors.

PMID- 12812745
TI  - Detecting environmental change in eastern Australia: rangeland health in the semi
      arid woodlands.
AB  - We examined changes in rangeland health in the semi-arid woodlands of eastern
      Australia at fixed sites between 1989 and 1999. Over the 11-year period there
      were significant declines in the quality of the vegetation, and changes in plant
      species were driven largely by seasonality, and to a lesser extent, amount of
      rainfall. Three indices of rangelands health (composition, function and
      stability) developed using site-based vegetation and landscape data, indicated
      that the majority of sites had intermediate values of the three indices, and few
      sites had either very low or very high values. The indices of composition and
      function were strongly correlated with the subjective ratings applied to each
      site at each measurement period. The results of this study highlight the
      difficulty of detecting change over extensive areas of rangeland, and of
      separating management-induced effects from climatic effects in an environment
      which experiences wide spatial and temporal variation in rainfall.

PMID- 12812746
TI  - The monitoring of British breeding birds: a success story for conservation
      science?
AB  - For almost four decades the British Trust for Ornithology has monitored
      populations of the commoner 35-50% of species of British breeding birds. The
      monitoring involves surveillance of numbers, breeding output and survival rates
      across the whole of the United Kingdom. A formal alert system allows serious
      declines to be identified and brought to the attention not only of
      conservationists and those responsible for countryside policy but also the
      general public. Demographic modelling, the gathering of ancillary information and
      linked research programmes allow the causes of declines to be identified. The
      paper details the operation of the programme, illustrated by examples. The system
      has resulted in the widespread declines in farmland birds that occurred in the
      last quarter of the 20th century being brought to the attention of conservation
      scientists, campaigners, policy-makers, politicians and the public. From this
      (and from the associated understanding of the causes of the declines) have
      stemmed policies aimed at reducing the problems and a commitment by government to
      halt the declines. The success of the programme rests on scientifically rigorous
      design and analysis, on a partnership between volunteer birdwatchers (who do most
      of the fieldwork) and professional ecologists (responsible for design and
      analysis) and on effective interaction between scientists and policy makers.

PMID- 12812747
TI  - The effects of variation in climatic temperature (1980-2001) on breeding activity
      and tadpole stage duration in the common toad, Bufo bufo.
AB  - The effects of variation in climatic temperature on breeding behaviour and
      tadpole growth were investigated using data collected during a 22-year study of a
      single population of common toads, Bufo bufo, in southern England. Although the
      start of the breeding season each year, taken as the day when adult toads first
      arrived at their breeding pond in large numbers, showed no trend over time (1980
      2001) it was highly correlated with climatic temperature. Thus, toads started
      breeding approximately 50 days earlier in the year following very mild winters
      (1993: February 2nd) compared with very cold ones (1986: March 23rd). Regression
      analysis of the relationship between the mean temperature of the 40 days
      immediately preceding the main arrival of toads at the breeding pond revealed
      that for every 1 degrees increase (or decrease) the toads arrived 12 days earlier
      (or later). Although the duration of the tadpole stage was longer when spawning
      was early, toadlets still emerged from the pond earlier than when spawning was
      late. The increased length of the tadpole stage, in years when spawning was
      early, was due to an increase in the proportion of cold days when the minimum
      ground temperature was at or below 0 degrees C. Thus, the tadpole stage was
      approximately 6 days longer (or shorter) for every 5% increase (or decrease) in
      the proportion of cold days the tadpoles were exposed to.

PMID- 12812748
TI  - A review of the possible impacts of long-term oceanic and climate changes and
      fishing mortality on recruitment of anguillid eels of the Northern Hemisphere.
AB  - Possible causes of declines in recruitment of European, American and Japanese
      eels to continental waters are reviewed. Negative correlations between the Den
      Oever glass eel recruitment index (DOI) and the North Atlantic Oscillation Index
      since 1938 are discussed, together with older anecdotal evidence. Correlations
      are established between the DOI and sea surface temperature anomalies at 100-250
      m between 1952 and 1995 in the Sargasso Sea/Sub-Tropical Gyre (STG) spawning
      area. It is hypothesised that, associated with global warming trends, STG warming
      inhibits spring thermocline mixing and nutrient circulation, with negative
      impacts on productivity and hence food for leptocephalus larvae. Concurrent gyre
      spin-up also affects major currents and slowing of oceanic migration has probably
      enhanced starvation and predation losses. Local factors, such as unfavourable
      wind-driven currents, can also affect recruitment of glass eels on continental
      shelves. In contrast, evidence is discussed that indicates fishing mortality and
      continental climate change appear to have had lesser impacts. Similar starvation
      advection explanations for declines in Japanese eel recruitment are proposed.
      Predictions for the future are made and multidisciplinary and integrated
      monitoring and research are recommended for managing eel stocks and fisheries.

PMID- 12812749
TI  - Detection of environmental change in a marine ecosystem--evidence from the
      western English Channel.
AB  - To separate human-induced changes from natural fluctuations in marine life
      requires long-term research. The western English Channel has been investigated
      from Plymouth for over 100 years. The abundance of marine life has been recorded
      and related to physical changes in the environment. By comparing different parts
      of the ecosystem we can demonstrate historic natural fluctuations, allowing
      prediction of effects of future global change. From the 1920s to the 1950s there
      was a period of warming of the sea, with increases in abundance of species of
      fish, plankton and intertidal organisms that are typically common in warmer
      waters to the south of Britain. After 1962 the sea cooled down and northern cold
      water species became more abundant. Since the 1980s regional sea surface
      temperature has increased again and warm-water species are once more becoming
      abundant.

PMID- 12812751
TI  - Robust generation of new hair cells in the mature mammalian inner ear by
      adenoviral expression of Hath1.
AB  - Although hair cells regenerate spontaneously in birds and lower vertebrates
      following injury, there is yet no effective way to stimulate hair cell
      regeneration in mature mammalian inner ears. Here we report that a large number
      of hair cells are produced in the sensory epithelium of cultured adult rat
      utricular maculae, via adenovirus-mediated overexpression of Hath1, a human
      atonal homolog. The generation of new hair cells via Hath1 expression does not
      involve cell proliferation based on bromodeoxyuridine immunocytochemistry.
      Furthermore, using a similar approach, hair cells are regenerated following
      aminoglycoside injury in these cultures. These data show conclusively that mature
      mammalian inner ears have the competence to produce a large number of new hair
      cells. Local adenoviral gene therapy in the inner ear may be a potential approach
      to treatment of hearing and balance disorders.

PMID- 12812750
TI  - Effects of coexpression with Homer isoforms on the function of metabotropic
      glutamate receptor 1alpha.
AB  - We previously showed that the metabotropic glutamate receptor 1alpha
      (mGluR1alpha) has a sensitivity to extracellular polyvalent cations such as
      Ca(2+) and Gd(3+) as well as glutamate. Here we show that mGluR1alpha-mediated
      responses to these ligands are modulated by the scaffold protein Homer. When
      HEK293 cells were transiently cotransfected with Homer 1c and mGluR1alpha, the
      maximum rate of rise and amplitude of glutamate-evoked [Ca(2+)](i) transients
      were increased and there was a rightward shift in the concentration-response
      relationship. The response of mGluR1alpha to abrupt increases in [Gd(3+)](o) was
      characteristic in that the concentration-response relationship was bell-shaped
      and Homer 1c broadened the effective range at both low and high concentrations.
      The effects of Homer 1a, which lacks clustering effect, differed qualitatively
      from those of Homer 1c. The effects of both Homer 1c and 1a on mGluR1alpha were
      decreased significantly in mGluR1alpha P1147E mutant which lacks the affinity to
      Homer, showing that the effects were mediated by binding to mGluR1alpha. Taken
      together, the binding of Homer 1c to mGluR1alpha was shown to cause not only an
      efficient link to Ca(2+)-store and a decrease in the surface expression, but also
      qualitative changes of the ligand-sensing function in a ligand type-specific
      manner.

PMID- 12812752
TI  - Persistent activation of p38 mitogen-activated protein kinase in a mouse model of
      familial amyotrophic lateral sclerosis correlates with disease progression.
AB  - The p38 mitogen-activated protein kinase (p38MAPK) is activated via
      phosphorylation in neurones and glial cells by a variety of stimuli including
      oxidative stress, excitotoxicity, and inflammatory cytokines. Activated p38MAPK
      can in turn induce phosphorylation of cytoskeletal proteins and activation of
      cytokines and nitric oxide, thus contributing to neurodegeneration. We
      investigated the expression and distribution of p38MAPK in the spinal cord of
      transgenic mice expressing a superoxide dismutase 1 mutation (SOD1G93A), a model
      of familial amyotrophic lateral sclerosis (ALS). Accumulation of p38MAPK was
      found by immunoblotting in the spinal cord of G93A mice during the progression of
      disease, but no changes were detected in its mRNA levels. Immunostaining for
      phosphorylated p38MAPK in lumbar spinal cord sections of SOD1G93A mice at the
      presymptomatic and early stages of disease showed an increased labeling in motor
      neurones that colocalized with phosphorylated neurofilaments in vacuolized
      perikarya and neurites, as detected by confocal microscopy. As the disease
      progressed, activated p38MAPK also accumulated in hypertrophic astrocytes and
      reactive microglia, as demonstrated by colocalization with GFAP and CD11b
      immunostaining, respectively. These data suggest that activation of p38MAPK in
      motor neurons and then in reactive glial cells may contribute, respectively, to
      the development and progression of motor neuron pathology in SOD1G93A mice.

PMID- 12812753
TI  - Tenascin-N: characterization of a novel member of the tenascin family that
      mediates neurite repulsion from hippocampal explants.
AB  - Tenascin-N, a novel member of the tenascin family, was identified and shown to
      encode characteristic structural motifs of a cysteine-rich stretch, 3.5 epidermal
      growth factor-like repeats, 12 fibronectin type III homologous domains, and a
      fibrinogen-like domain. The third fibronectin type III homologous domain is
      altered by RNA splicing. Characterization of the expression of tenascin-N by in
      situ hybridization analysis assigned transcripts to many types of neurons in the
      central nervous system, to the medullary region in the kidney, and to resident
      macrophages of the T-cell zone in the splenic white pulp. By
      immunohistochemistry, tenascin-N expression is detectable in all brain regions,
      with a characteristic staining pattern in the hippocampus demarcating the CA3
      region. Recombinantly expressed protein fragments of the alternatively spliced
      isoforms were presented in choice assays on patterned substrates to neurites and
      migrating neurons from hippocampal CA3 region explant cultures. The smaller
      splice variant inhibited neurite outgrowth or cell migration, whereas the longer
      splice form did not inhibit these functions. These observations suggest that the
      novel tenascin family member mediates specific repulsive properties on neurites
      and neurons by generating splice isoforms.

PMID- 12812754
TI  - Schwann cells synthesize alpha7beta1 integrin which is dispensable for peripheral
      nerve development and myelination.
AB  - Defects in laminins or laminin receptors are responsible for various
      neuromuscular disorders, including peripheral neuropathies. Interactions between
      Schwann cells and their basal lamina are fundamental to peripheral nerve
      development and successful myelination. Selected laminins are expressed in the
      endoneurium, and their receptors are developmentally regulated during peripheral
      nerve formation. Loss-of-function mutations have confirmed the importance and the
      role of some of these molecules. Here we show for the first time that another
      laminin receptor, alpha7beta1 integrin, previously described only in neurons, is
      also expressed in Schwann cells. The expression of alpha7 appears postnatally,
      such that alpha7beta1 is the last laminin receptor expressed by differentiating
      Schwann cells. Genetic inactivation of the alpha7 subunit in mice does not affect
      peripheral nerve formation or the expression of other laminin receptors. Of note,
      alpha7beta1 is not necessary for basal lamina formation and myelination.
      Nonetheless, these data taken together with the previous demonstration of
      impaired axonal regrowth in alpha7-null mice suggest a possible Schwann cell
      autonomous role for alpha7 in nerve regeneration.

PMID- 12812755
TI  - Human melanoma/NG2 chondroitin sulfate proteoglycan is expressed in the
      sarcolemma of postnatal human skeletal myofibers. Abnormal expression in merosin
      negative and Duchenne muscular dystrophies.
AB  - NG2 is the rat homologue of the human melanoma chondroitin sulfate proteoglycan
      (MCSP) preferentially expressed in dividing progenitor cells of the glial and
      mesenchymal lineage but downregulated after differentiation. It has recently been
      demonstrated that MCSP/NG2 expression is not restricted to mitotic or malignant
      cells. We show that MCSP/NG2 expression is detectable in the sarcolemma, and in
      the neuromuscular junction of human postnatal skeletal muscle, and it gradually
      reduces with advancing age. In human and murine myogenic cell lines, we found no
      clear differences in MCSP/NG2 expression between myoblasts and myotubes. Reduced
      levels of the core protein were found in merosin-negative congenital muscular
      dystrophy (MDC1A). Duchenne muscular dystrophy patients muscles exhibited an
      overexpression of the MCSP/NG2 core protein. In gamma-sarcoglycanopathy and
      calpainopathy, MCSP/NG2 upregulation was restricted to regenerating myofibers. We
      demonstrate that MCSP/NG2 is expressed in differentiated myofibers, and appears
      to have a role in the pathogenesis of MDC1A and severe dystrophinopathies.

PMID- 12812756
TI  - Lumbar 5 ventral root transection-induced upregulation of nerve growth factor in
      sensory neurons and their target tissues: a mechanism in neuropathic pain.
AB  - We have previously demonstrated that profound and persistent neuropathic pain as
      displayed by mechanical and cold allodynia and thermal hyperalgesia can be
      produced by a lumbar 5 ventral root transection (L5 VRT) model in adult rats in
      which only the motor nerve fibers were injured without axotomy of sensory
      neurons. However, the underlying mechanisms remain to be determined. In this
      study, by examining its changes in expression and by inhibiting its functions
      using a neutralizing antibody, we have investigated whether nerve growth factor
      (NGF), a neurotrophic factor known to have a function in regulating nerve injury
      induced pain, is involved in the development of neuropathic pain induced by L5
      VRT. Motor nerve injury by L5 VRT resulted in a de novo expression of NGF mRNA in
      a subpopulation of small sensory neurons and pericellular satellite cells in
      ipsilateral L5 dorsal root ganglion. NGF protein expression was also increased by
      sensory neurons with various sizes and by keratinocytes in the target tissue
      ipsilateral skin. Systemic administration of NGF antiserum twice within 17 days
      markedly attenuated L5 VRT-induced mechanical allodynia but not the cold
      allodynia and thermal hyperalgesia. These findings suggest that NGF is an
      important pain mediator in the generation of mechanical sensitivity induced by L5
      VRT.

PMID- 12812757
TI  - Immunization with myelin or recombinant Nogo-66/MAG in alum promotes axon
      regeneration and sprouting after corticospinal tract lesions in the spinal cord.
AB  - We have shown previously that immunization with myelin in incomplete Freund's
      adjuvant (IFA) is able to promote robust regeneration of corticospinal tract
      fibers in adult mice. In the present study the effectiveness of such immunization
      with myelin was compared to that of a combination of two axon growth inhibitors
      in myelin, Nogo-66 (the 66-amino-acid inhibitory region of Nogo-A) and myelin
      associated glycoprotein (MAG). The effectiveness of two adjuvants, IFA and
      aluminum hydroxide (Alum), was also compared, the latter being one that can be
      used in humans. In addition, larger dorsal overhemisections were made at the
      lower thoracic level, which resulted in a larger scar. These studies were carried
      out in SJL/J mice, a mouse strain that is susceptible to autoimmune experimental
      allergic encephalomyelitis (EAE). None of the immunized mice developed EAE. Long
      distance axon regeneration and sprouting of the corticospinal tract was seen in
      myelin and Nogo-66/MAG immunized mice. Alum was as effective or better than IFA
      as the adjuvant. Overall, the robustness of axon growth and sprouting was greater
      in mice immunized with myelin. The abundance of this growth was less than in our
      earlier work in which smaller lesions were made, pointing to the possible
      influence of inhibitors in the scar. This work shows, however, that axon growth
      inhibitors in myelin can be selectively blocked using this immunization approach
      to promote long-distance axon regeneration in the spinal cord.

PMID- 12812758
TI  - Association of gephyrin with synaptic and extrasynaptic GABAA receptors varies
      during development in cultured hippocampal neurons.
AB  - Several studies have reported extrasynaptic clusters of GABAA receptors in
      hippocampal neurons. Yet their functional relevance as well as their evolution in
      relation with gephyrin during synaptogenesis remain unknown. We have analyzed the
      expression pattern of the main proteins of the GABAergic synapses during
      synaptogenesis in cultured hippocampal neurons. We found that GABAergic
      terminals, characterized by VIAAT and GAD-65 expression, differentiated 3 to 7
      days after the glutamatergic endings. At the postsynaptic side, the GABAAR- beta3
      subunit was first diffuse and then clustered when GABAergic terminals
      differentiated and gephyrin formed large clusters. Colocalization of these
      proteins was high and increased with development. At later stages, GABAAR beta3
      clusters colocalized with gephyrin at synaptic but also at extrasynaptic sites.
      GABAAR gamma2 subunits were directly expressed as clusters which were first
      extrasynaptic and not associated with gephyrin. Subsequently, the GABAAR gamma2
      subunits associated with gephyrin at synaptic and/or extrasynaptic sites. Our
      data indicate that formation of GABAAR gamma2 subunit clusters is gephyrin
      independent.

PMID- 12812759
TI  - Functional regions of the presynaptic cytomatrix protein bassoon: significance
      for synaptic targeting and cytomatrix anchoring.
AB  - Exocytosis of neurotransmitter from synaptic vesicles is restricted to
      specialized sites of the presynaptic plasma membrane called active zones. A
      complex cytomatrix of proteins exclusively assembled at active zones, the CAZ, is
      thought to form a molecular scaffold that organizes neurotransmitter release
      sites. Here, we have analyzed synaptic targeting and cytomatrix association of
      Bassoon, a major scaffolding protein of the CAZ. By combining immunocytochemistry
      and transfection of cultured hippocampal neurons, we show that the central
      portion of Bassoon is crucially involved in synaptic targeting and CAZ
      association. An N-terminal region harbors a distinct capacity for N
      myristoylation-dependent targeting to synaptic vesicle clusters, but is not
      incorporated into the CAZ. Our data provide the first experimental evidence for
      the existence of distinct functional regions in Bassoon and suggest that a
      centrally located CAZ targeting function may be complemented by an N-terminal
      capacity for targeting to membrane-bounded synaptic organelles.

PMID- 12812760
TI  - Proliferation of neural and neuronal progenitors after global brain ischemia in
      young adult macaque monkeys.
AB  - To investigate the effect of global cerebral ischemia on brain cell proliferation
      in young adult macaques, we infused 5-bromo-2'-deoxyuridine (BrdU), a DNA
      replication indicator, into monkeys subjected to ischemia or sham-operated.
      Subsequent quantification by BrdU immunohistochemistry revealed a significant
      postischemic increase in the number of BrdU-labeled cells in the hippocampal
      dentate gyrus, subventricular zone of the temporal horn of the lateral ventricle,
      and temporal neocortex. In all animals, 20-40% of the newly generated cells in
      the dentate gyrus and subventricular zone expressed the neural progenitor cell
      markers Musashi1 or Nestin. A few BrdU-positive cells in postischemic monkeys
      were double-stained for markers of neuronal progenitors (class III beta-tubulin,
      TUC4, doublecortin, or Hu), neurons (NeuN), or glia (S100beta or GFAP). Our
      results suggest that ischemia activates endogenous neuronal and glial precursors
      residing in diverse locations of the adult primate central nervous system.

PMID- 12812761
TI  - Transgenic mice overexpressing XIAP in neurons show better outcome after
      transient cerebral ischemia.
AB  - X-chromosome linked inhibitor of apoptosis protein (XIAP) is a member of the
      inhibitor of apoptosis protein (IAP) family and known to inhibit death of various
      cells under different experimental conditions. Although present in brain tissue,
      little is known about the physiology of the IAPs in nerve cells. Here we report
      on the establishment of transgenic mice with overexpression of human XIAP in
      brain neurons. The mice developed normally, and were more resistant to brain
      injury caused by transient forebrain ischemia after occlusion of the middle
      cerebral artery compared to control mice. The XIAP transgenic animals exhibited
      significantly smaller brain damage, as shown by TUNEL labelling, less reduction
      in brain protein synthesis, and less active caspase-3 after ischemia compared
      with controls. Upregulation of RhoB, which is an early indicator of neurological
      damage, was markedly reduced in the XIAP-overexpressing mice, which had also a
      better neurological outcome than control animals. This together with the increase
      in XIAP in normal mouse brain in regions surviving the infarct demonstrates that
      XIAP is an important factor promoting neuronal survival after ischemia. The
      results suggest that interference with the levels and the activity of XIAP in
      neurons may provide targets for the development of drugs limiting neuronal death
      after ischemia, and possibly in other brain injuries.

PMID- 12812762
TI  - A tyrosine residue in TM6 of the Vanilloid Receptor TRPV1 involved in
      desensitization and calcium permeability of capsaicin-activated currents.
AB  - The Vanilloid Receptor TRPV1 is a non-selective cation channel with a high
      relative Ca(2+) permeability. TRPV1 exhibits slow desensitization, a potential
      mechanism regulating adaptation of peripheral sensory neurons to noxious stimuli.
      The predicted folding pattern of TRPV1 resembles that of voltage-gated channels.
      Sequence alignment of segments 6 of TRPV1 and voltage-gated Na(+) channels
      reveals a conserved aromatic amino acid that in Na(+) channels is involved in
      fast inactivation and pharmacological block. We found that replacing this
      tyrosine Y671 by positively charged lysine (K) completely abrogated Ca(2+)
      dependent desensitization. Y671K also exhibited significant reduction in Ca(2+)
      permeability that was not responsible for the lack in desensitization.
      Substitution of Y671 with negatively charged aspartate or uncharged alanine
      slightly altered desensitization but left Ca(2+) permeability unchanged.
      Substitution of Y671 with positively charged arginine produced a phenotype
      similar to Y671K. We propose that residue Y671 is critical for the high relative
      Ca(2+) permeability of TRPV1 and participates in the structural rearrangements of
      the channel protein leading to Ca(2+)-dependent desensitization.

PMID- 12812763
TI  - Calcineurin controls the expression of numerous genes in cerebellar granule
      cells.
AB  - The Ca(2+)/calmodulin-dependent phosphatase calcineurin plays a crucial role in
      gene expression in different cell types such as T-lymphocytes, cardiac myocytes,
      and smooth muscle cells. A possible role for calcineurin in gene expression was
      recently found in neurons, where calcineurin regulates the expression of several
      genes involved in Ca(2+) homeostasis. To detect additional genes regulated in a
      calcineurin-dependent way in neurons we analysed gene expression profiles of
      cerebellar granule cells cultured in depolarising conditions in the presence or
      absence of the calcineurin inhibitory agents FK506 and CsA. Using oligonucleotide
      arrays we identified 34 genes that are differentially expressed between the
      samples and confirmed the calcineurin-dependent regulation of some of these genes
      by RT-PCR. Therefore, our results, which are likely not to be comprehensive,
      suggest that calcineurin plays a fundamental role in neuronal gene expression by
      either activating or repressing the expression of genes such as receptors,
      transcription factors, and signalling molecules.

PMID- 12812764
TI  - Neurochemical correlates of male polymorphism and alternative reproductive
      tactics in the Azorean rock-pool blenny, Parablennius parvicornis.
AB  - In the common Azorean rock-pool blenny, Parablennius parvicornis, males exhibit
      alternative reproductive morphologies: (1) larger males defend nest sites,
      provide parental care, have anal glands (involved in pheromone release),
      testicular glands, and low gonad:body weight ratio (GSI) and (2) smaller,
      younger, males do not defend nests, have reduced glands and high GSI. These
      smaller non-nesting males behave as satellites (associated with nests) or
      sneakers (moving among nests), attempting to achieve parasitic fertilizations via
      sperm competition. In non-mammals, arginine vasotocin (AVT) is a key hypothalamic
      peptide involved in the control of reproductive behavior and physiology, and
      several fish species that exhibit alternative male reproductive morphs show
      polymorphism in AVT brain chemistry. We conducted an immunocytochemical study to
      generate comparative data on this intertidal blenny. Our analysis showed no
      difference in AVT-immunoreactive cell number or size between the male morphs,
      which is consistent with studies on other fish, including blennies. The number of
      AVT cells was positively correlated to fish body mass, while cell size showed no
      such relation. If corrected for body mass, the smaller non-nesting males have
      significantly more cells than the large nesting males. Our data suggest that the
      size and number of forebrain AVT cells develops initially to allow for
      reproduction in the young non-nesting males and this pattern does not appear to
      change when males take on the nesting morphotype later in life. This result
      appears to be consistent in many fishes with alternative male morphotypes.

PMID- 12812765
TI  - Handling during pregnancy in the blue fox (Alopex lagopus): the influence on the
      fetal gonadal function.
AB  - In previous studies it has been shown that handling produced stress in pregnant
      blue fox vixens increasing plasma level and adrenal in vitro production of
      cortisol. Moreover, this treatment increased plasma cortisol levels in the
      fetuses. The present study was designed to examine effects of a 1-min daily
      handling stress applied to pregnant blue fox vixens on fetal gonadal
      steroidogenesis. Plasma concentrations of oestradiol and testosterone, gonadal
      content and gonadal in vitro production of these steroids, and response to
      exogenous hCG as well as gonadal weights, and anogenital distances were measured
      in control (C, n=69) and stressed (S, n=54) fetuses on 47-48 days of pregnancy.
      Maternal stress induced a suppression of gonadal steroidogenesis in the fetuses.
      The decreased testosterone content in the testes and oestradiol content in the
      ovaries were demonstrated in stressed fetuses compared with control
      (testosterone: 4.91+/-0.46 vs. 7.35+/-0.87 ng/both testes, P<0.05; oestradiol:
      29.1+/-3.4 vs. 46.5+/-4.9 ng/both ovaries, P<0.05). The ovarian oestradiol in
      vitro production in female fetuses from stressed mothers was decreased in
      comparison with control (3.69+/-0.39 vs. 7.52+/-1.51 pg/ovary/h, P<0.05). The
      same difference was observed between stressed and control male fetuses in the
      testosterone testicular response to hCG (5.34+/-0.64 vs. 8.73+/-0.40 ng/testis/h,
      P<0.05). The ovarian weight from stressed fetuses was lower in comparison with
      control (12.9+/-0.7 vs. 16.8+/-0.6 mg, P<0.05). The anogenital distance in female
      fetuses from stressed vixens was also reduced (0.6+/-0.03 vs. 0.8+/-0.02 cm,
      P<0.01). These results indicate that prenatal stress resulted in a significant
      reduction of hormonal and morphometric measures of the reproductive system in
      blue fox fetuses with more drastic effects in female fetuses.

PMID- 12812766
TI  - Response by the corpuscles of Stannius to hypotensive stimuli in three divergent
      ray-finned fishes (Amia calva, Anguilla rostrata, and Catastomus commersoni):
      cardiovascular and morphological changes.
AB  - In accordance with their vital role in cardiovascular physiology () corpuscles of
      Stannius (CS) from two teleosts and an holostean species showed marked and
      consistent degranulation and exocytotic responses to hypotensive stimuli. In eels
      (Anguilla rostrata LeSueur) acute blood withdrawal (hypovolemic hypotension) was
      followed by a prompt decrease in cardiac output (CO) and dorsal aortic pressure
      (P(DA)), a compensatory tachycardic response and an increase in systemic vascular
      resistance (R(SYS)). Isovolemic hypotension induced by papaverine i.v., led to a
      similar, but more prolonged, decrease in P(DA) but the heart rate (HR) continued
      to accelerate, thereby counterbalancing the severe and persistent decrease in
      R(SYS). Both hypovolemic and isovolemic hypotension were followed by a
      significant depletion of cytoplasmic granules from eel CS even though plasma
      concentrations of Ca, Mg, Na(+), and K(+) were normal. In an ancient holostean
      fish, the bowfin, Amia calva and a generalized teleost fish, Catastomus
      commersoni, the number of cytoplasmic granules decreased by 39% and 54%,
      respectively, 120 min after the acute withdrawal of 8 ml kg bw(-1) of blood.
      These findings suggest that a primary role of the CS is to release cytoplasmic
      granules containing renin or isorenin into the blood circulation, in response to
      hypotension and/or hypovolemia.

PMID- 12812767
TI  - Effect of refeeding on IGFI, IGFII, IGF receptors, FGF2, FGF6, and myostatin mRNA
      expression in rainbow trout myotomal muscle.
AB  - Fish endure long periods of fasting and demonstrate an extensive capacity for
      rapid and complete recovery after refeeding. The underlying mechanisms through
      which nutrient intake activates an increase in somatic growth and especially in
      muscle growth is poorly understood. In this study we examined the expression
      profile of major muscle growth regulators in trout white muscle 4, 12, and 34
      days after refeeding, using real-time quantitative RT-PCR. Mean insulin-like
      growth factor I (IGFI) mRNA level in muscle increased dramatically 8- and 15
      fold, 4 and 12 days, respectively, after refeeding compared to fasted trout. This
      declined thereafter. Conversely, only a weak but gradual increase in mean insulin
      like growth factor II (IGFII) mRNA level was observed during refeeding. Inversely
      to IGFI, mean IGF receptor Ia (IGFRIa) mRNA level declined after ingestion of
      food. In contrast, IGF receptor Ib (IGFRIb) mRNA level was not affected by
      refeeding. Mean fibroblast growth factor 2 (FGF2) mRNA level increased by 2.5
      fold both 4 and 12 days after refeeding, whereas fibroblast growth factor 6
      (FGF6) and myostatin mRNA levels were unchanged. Subsequent to IGFI and FGF2 gene
      activation, an increase in myogenin mRNA accumulation was observed at 12 days
      post-refeeding suggesting that an active differentiation of myogenic cells
      succeeds their proliferation. In conclusion, among the potential growth factors
      we examined in this study, IGFI and FGF2 were identified as candidate genes whose
      expression may contribute to muscle compensatory growth induced by refeeding.

PMID- 12812768
TI  - Effect of tidal cycle and food intake on the baseline plasma corticosterone
      rhythm in intertidally foraging marine iguanas.
AB  - In most species, plasma levels of baseline glucocorticoids such as corticosterone
      (B) have a circadian rhythm. This rhythm can be entrained by both photoperiod and
      food intake and is related to aspects of energy intake and metabolism. Marine
      iguanas (Amblyrhynchus cristatus) offer a unique opportunity to better understand
      the relative importance of the light:dark cycle versus food intake in influencing
      the rhythm in baseline B in a natural system. Compared to other species, food
      intake is not as strictly determined by the phase of the light:dark cycle.
      Animals feed in the intertidal zone so feeding activity is heavily influenced by
      the tidal cycle. We measured baseline plasma B levels in free-living iguanas over
      several 24-h periods that varied in the timing of low tide/foraging activity. We
      found that baseline B levels were higher during the day relative to night.
      However, when low tide occurred during the day, baseline B levels dropped
      coincident with the timing of low tide. Whether the baseline B rhythm (including
      the drop during foraging) is an endogenous rhythm with a circatidal component, or
      is simply a result of feeding and associated physiological changes needs to be
      tested. Together, these data suggest that the baseline B rhythm in marine iguanas
      is influenced by the tidal cycle/food intake as well as the light:dark cycle.

PMID- 12812769
TI  - Aromatase activity in the European sea bass (Dicentrarchus labrax L.) brain.
      Distribution and changes in relation to age, sex, and the annual reproductive
      cycle.
AB  - Cytochrome P450 aromatase activity (AA) was measured in different tissues of the
      sea bass (Dicentrarchus labrax L.) using a tritiated water release assay that was
      previously optimized and validated for this species. In adult fish entering the
      reproductive season, AA was highest on a per mg protein basis, in the brain
      (2.04+/-0.4 pmol/mg prot/h; mean+/-SEM), followed by the ovary (0.59+/-0.1) and
      was detectable in visceral fat (0.21+/-0.05), liver (0.08+/-0.009), and head
      kidney (0.03+/-0.004). However, AA was negligible in the rest of the tissues
      tested: heart, testis, muscle, and spleen. Consistent with results obtained in
      other species, dissection of the brain into its major constitutive parts revealed
      that AA was concentrated in areas implicated in the control of reproduction,
      including the olfactory bulb, telencephalon, and hypothalamus (range: 2.6-16.2
      pmol/mg prot/h), as well as the pituitary gland (6.2-9.3 pmol/mg prot/h). Lower
      AA was noted in the optic bulb, cerebellum, and medulla. However, in contrast to
      some previously published reports concerning the content and distribution of
      neural aromatase in fish, males consistently exhibited higher AA than females. In
      one-year-old juvenile fish completing the process of gonadal sex differentiation,
      brain AA (0.63 pmol/mg prot/h) was similar in both sexes and ten times lower than
      that measured in the brain of first time spawners (6.52 pmol/mg prot/h), in this
      case with males showing an overall higher (24%) activity than females. When
      surveyed throughout the year, brain AA dramatically changed during the
      reproductive cycle. Maximum average values of approximately 7 pmol/mg prot/h were
      obtained that coincided with the spawning season. The peak in brain AA was
      preceded by two and one months by the peak of plasma testosterone and the peak of
      the gonadosomatic index, respectively. This is the first measurement of the
      distribution of the activity of a steroidogenic enzyme in the sea bass, an
      established model in comparative endocrinology. Together, these results
      demonstrate sex- and seasonally-related variations in AA and establish the basis
      for further comparative studies of certain androgen-mediated actions through
      locally formed estrogen in both central and peripheral targets.

PMID- 12812770
TI  - Specific cell surface binding sites shared by human Pro-IGF-I Eb-peptides and
      rainbow trout Pro-IGF-I Ea-4-peptide.
AB  - Human pro-IGF-I Eb-peptide (hEb) and rainbow trout pro-IGF-I Ea-4-peptide (rtEa
      4) have recently been shown to share unique biological activities [Gen. Comp.
      Endocrinol. 126 (2002) 342; Cell. Exp. Cell. Res. 280 (2002) 75]. To further
      understand the action mechanism of these proteins, we studied the binding
      properties of hEb-peptide and rtEa-4-peptide to intact human neuroblastoma cells
      (SK-N-F1) and membrane preparations. Human Eb-peptide and rtEa-4-peptide bind to
      a high-affinity binding site with an apparent dissociation constant of 3.2+/-1.9
      x 10(-11) and 2.9+/-1.8 x 10(-11)M, respectively. Homologous displacement assay
      demonstrated the presence of a second binding site with an IC(50) of 4.8+/-2.6 x
      10(-6)M for hEb-peptide and 2.1+/-0.6 x 10(-6)M for rtEa-4-peptide, respectively.
      Competition assays showed that hEb-peptide and rtEa-4-peptide shared common
      binding sites, distinct from those for IGF-I and insulin. In addition, chemical
      cross-linking studies revealed two specific binding complexes. Our findings
      support the notion that the initial step of pro-IGF-I E-peptide action is
      mediated through the interaction with conserved and specific putative membrane
      receptors on neuroblastoma cells.

PMID- 12812771
TI  - Maternal androgens in egg yolks: relation with sex, incubation time and embryonic
      growth.
AB  - Hormones of maternal origin are known to be transferred to the egg yolks of
      oviparous species. Several studies have shown that within and between clutch
      variation of maternal androgens may be adaptively tuned. Moreover, it has
      recently been hypothesized that sex steroids of maternal origin may play a role
      in adaptive sex ratio manipulation. For sex determination the eggs have to be
      incubated to allow the germinal disc to grow and thus extract sufficient DNA.
      This means that yolk hormone levels are determined after a number of days of
      incubation and this may hamper interpretation of the data. If yolk utilization or
      embryonic hormone production are influenced by the sex of the embryo, differences
      in hormone content at a certain stage of incubation do not reflect the mother's
      initial allocation. In this experiment we show that testosterone levels in
      chicken eggs do not change with incubation period. A4 levels decrease between 3
      and 5 days of incubation, which we cannot explain. Male eggs did not contain
      higher levels of testosterone or androstenedione than female eggs, in contrast to
      the data reported for another galliform species, the peacock. We conclude that it
      is unlikely that maternal androgens are a key factor in the avian sex
      determination mechanism.

PMID- 12812772
TI  - Vitellogenin synthesis via androgens in primary cultures of tilapia hepatocytes.
AB  - Involvement of androgens in vitellogenin (VTG) synthesis was investigated using
      the primary hepatocyte cultures of tilapia, Oreochromis mossambicus.
      Concentration of VTG in the medium was assessed by enzyme-linked immunosorbent
      assay. When the hepatocytes of females were treated with testosterone (T), 17
      alpha-methyltestosterone (MT) and 5 alpha-dihydrotestosterone (DHT), VTG
      concentration in the medium slightly increased or maintained. DHT, but not T and
      MT, increased VTG in the medium of male hepatocyte cultures. However, VTG
      production in the male hepatocytes, which were previously treated with estradiol
      17 beta (E(2)), maintained high level by treatment of T. Similarly, co-treatment
      of E(2) and the androgens to the male hepatocytes enhanced VTG concentration in
      the medium. These results suggest that the androgens have some roles in VTG
      synthesis in the hepatocytes. Tamoxifen, a nonsteroidal antiestrogen, reduced VTG
      synthesis by the androgens. On the other hand, co-treatment of T and fadrozole,
      an aromatase inhibitor, failed to inhibit the effect of VTG synthesis by T alone.
      Analysis with RT-PCR did not demonstrate expression of the brain and the ovarian
      types of aromatase mRNA in the liver. These results suggest that the possibility
      of local aromatization of the androgens in the tilapia liver is low and that
      androgens bind estrogen receptor and, consequently, exert estrogenic action.
      Treatment of cyproterone acetate, an antiandrogen reagent, increased production
      of VTG with DHT. Involvement of androgens might not be ignored in regulation of
      VTG synthesis in the liver.

PMID- 12812773
TI  - Cortisol treatment affects glucocorticoid receptor and glucocorticoid-responsive
      genes in the liver of rainbow trout.
AB  - We investigated whether longer-term cortisol exposure modified hepatic
      glucocorticoid receptor (GR) status and tissue responsiveness to cortisol
      stimulation in rainbow trout. Fish were given intraperitoneal implants of
      cortisol (50mg/kg body mass) and this led to elevated plasma cortisol levels
      mimicking chronically stressed salmonids. There was significantly higher hepatic
      GR mRNA abundance, despite a drop in GR protein content in the liver of cortisol
      treated fish. The tissue responsiveness to cortisol stimulation was apparent from
      the higher plasma glucose concentration and liver glycogen content. Also, the
      higher phosphoenolpyruvate carboxykinase (PEPCK) mRNA abundance, a key
      glucocorticoid-responsive gene, by cortisol suggests activation of the GR
      signalling pathway. There was no significant effect of cortisol treatment on
      liver PEPCK, alanine aminotransferase, aspartate aminotransferase, and lactate
      dehydrogenase activities compared to the sham fish. The higher heat shock protein
      (hsp) 90 mRNA abundance and a corresponding elevation in this protein and
      constitutive hsp70 (hsc70) protein content in the cortisol-treated fish reflects
      a role for glucocorticoids in the hepatic stress response process. Taken
      together, the molecular and biochemical responses evident in the liver of trout
      imply changes favouring tissue responsiveness to glucocorticoids and may be a
      mechanism to offset GR protein downregulation evident with chronic cortisol
      stimulation in rainbow trout.

PMID- 12812774
TI  - Concentrations of four fecal steroids in wild baboons: short-term storage
      conditions and consequences for data interpretation.
AB  - One source of both bias and "noise" in fecal steroid analysis is temporal change
      in steroid concentrations resulting from duration or conditions of fecal sample
      storage. However, no consensus currently exists regarding correct procedures or
      precautions necessary for fecal sample storage, and conditions vary widely within
      field endocrinology literature. This study considered the effects of short-term,
      weeks-long, storage conditions on quantifiable fecal testosterone (fT),
      glucocorticoids (fGC), estrogens (fE), and progestagen (fP) metabolite
      concentrations in wild baboons (Papio cynocephalus). Quadruplicate subsamples of
      fecal samples (n=29) collected at Amboseli National Park and its environs were
      subjected to four different storage conditions prior to lyophilization, in order
      to determine the effects of storage on subsequent steroid concentrations, as
      assessed by 125I radioimmunoassays. As expected, the best alternative to the
      "initial condition" of lyophilization at three days after collection was to
      freeze fecal samples at -20 degrees C for two weeks prior to lyophilization. This
      storage method resulted in no significant change from initial steroid
      concentrations for fE, fT, or fP, although fGC showed a slight but significant
      decline. Storage for two weeks in a charcoal refrigerator caused a mean increase
      in all four steroid concentrations. However, the results from this storage
      condition were robust in terms of practical questions asked of the data: fE and
      fP values still reflected pregnant versus non-pregnant states in baboon females;
      a fGC profile constructed by age class resembled that created from the samples
      from the initial condition, although slightly inflated across age classes; and
      there were only moderate changes in relative fT concentrations across adult
      males. Knowledge of the effects of storage upon each steroid analyzed within
      one's study is a necessary component in determining the optimal compromise for
      storage protocol in a particular research project.

PMID- 12812775
TI  - In vitro study of corticotropin-releasing hormone-induced thyrotropin release:
      ontogeny and inhibition by somatostatin.
AB  - Recent research has shown that in the chicken important interactions take place
      between the adrenal and the thyroidal axis both at the central and the peripheral
      level. In vivo as well as in vitro experiments showed that ovine corticotropin
      releasing hormone (oCRH) clearly increases thyrotropin (TSH) secretion in late
      embryonic and early posthatch chicks. In vivo experiments in older chickens,
      however, suggested that this response might disappear at a later stage. Therefore
      we started to study in detail the ontogeny of the TSH releasing activity of oCRH
      using the in vitro perifusion technique. Several embryonic stages (E14, E16, and
      E18) as well as posthatch stages (C1, C8, C22, and adult chickens) were included
      in the study. We also investigated the possible regulatory role of somatostatin
      (SRIH) in this specific endocrine function of CRH. The perifusion studies show
      that CRH stimulated the TSH release at all stages tested. The 10 and 100 nM oCRH
      doses were almost equally effective at the early embryonic stages while in most
      posthatch stages the higher oCRH dose was significantly more effective than the
      lower one. The stimulation factor, representative for the relative increase in
      TSH secretion following oCRH challenge, was high at early embryonic stages and
      clearly lower in adult animals. This seemed to be related to an age-dependent
      increase in basal TSH secretion levels. In both embryonic (E19) and posthatch
      (C8) chicks a pretreatment of the pituitaries with SRIH lowered the sensitivity
      of the thyrotropes to an oCRH challenge. This effect was more pronounced in the
      posthatch chicks compared to the embryos. The results show that CRH is capable of
      stimulating the TSH secretion during the entire life cycle of the chicken and
      that SRIH may play an important role in the fine-tuning of this response by
      lowering the sensitivity of the thyrotropes to CRH.

PMID- 12812776
TI  - Localization of the neuronal form of nitric oxide synthase (bNOS) in the
      diencephalon and pituitary gland of the catfish, Synodontis multipunctatus: an
      immunocytochemical study.
AB  - The distribution of the neuronal form of nitric oxide synthase (bNOS) was
      investigated in the brain and pituitary gland of the catfish, Synodontis
      multipunctatus. Immunoreactive neurons were found mainly in the nucleus
      praeopticus periventricularis, the parvocellular and supraoptic subdivisions of
      the nucleus praeopticus, the nucleus recessus lateralis and the nucleus recessus
      posterioris. In addition, some scattered bNOS labeled somata were noted in the
      dorsal hypothalamic area. A few positive cells in the adenohypophysis and some
      reactive fibers in the pituitary stalk were also seen. Our results are compatible
      with the notion that the cells expressing bNOS in the diencephalon and hypophysis
      are involved in the control of hormone regulation. Moreover, the presence of bNOS
      positive cells in the rostral pars distalis of the pituitary gland supports a
      role of nitric oxide in osmoregulation.

PMID- 12812777
TI  - In vitro effect of leptin on somatolactin release in the European sea bass
      (Dicentrarchus labrax): dependence on the reproductive status and interaction
      with NPY and GnRH.
AB  - The aim of the present work was to investigate the neuroendocrine control of
      pituitary somatolactin (SL) release using dispersed pituitary cell culture
      obtained from male European sea bass (Dicentrarchus labrax) at different stages
      of sexual development. The effect of mouse recombinant leptin, sea bream
      gonadotropin releasing-hormone (sbGnRH) and porcine neuropeptide Y (pNPY) and
      their potential interaction on the SL release were investigated. High doses of
      leptin (10(-8)-10(-6)M) were differentially effective in inducing SL release
      depending on the sexual developmental stage. Porcine NPY alone was not effective
      on basal SL release, but it dose-dependently (0.1 and 1 nM) enhanced SL release
      induced by leptin (10(-6) and 10(-8)M) in late pre-pubertal but not in post
      pubertal stages. No effect of sbGnRH in association or not with leptin was
      observed on SL release. These findings are the first evidences that leptin and
      pNPY can play an important role in the neuroendocrine control of pars intermedia
      function and SL release in fish. In addition, the sensitivity of SL producing
      cells to leptin and NPY only in prepubertal and pubertal stages, provides the
      potential role of SL in the nutritional control of the onset of puberty.

PMID- 12812778
TI  - Immunohistochemical localization of chromogranin A in gonadotrophs and
      somatotrophs of the turkey and chicken pituitary.
AB  - In the course of producing monoclonal antibodies to turkey prolactin, three
      monoclonal antibodies to turkey chromogranin A (CgA) were also produced,
      apparently arising from minor contamination of the turkey prolactin immunogen
      with peptide fragments of CgA. The identity of the antigen recognized by these
      antibodies was established by tandem mass spectrometry de novo sequencing of
      seven tryptic peptides from a turkey pituitary protein purified by immunoaffinity
      chromatography. These peptides showed high homology with distinctly separate
      regions of mammalian and ostrich CgA, and in silico cloned chicken CgA sequences.
      Chromogranin A immunostaining patterns on Western blots and pituitary tissue
      sections differed from those of prolactin, growth hormone, or luteinizing hormone
      (LH). Dual-label fluorescent immunohistochemistry revealed that CgA was co
      localized with LH in most avian gonadotrophs in young chickens and turkeys, but
      not in adult, laying birds. Conversely, CgA was found in a majority of
      somatotrophs in laying birds but was absent from somatotrophs in young, growing
      chickens and turkeys. Lactotrophs contained no detectable CgA immunoreactivity in
      the tissues studied. These results suggest that CgA may modulate hormone
      secretion by gonadotrophs and somatotrophs in a manner that differs between cell
      type with age or reproductive state.

PMID- 12812779
TI  - Developmental ontogeny of prolactin and prolactin receptor in the sea bream
      (Sparus aurata).
AB  - The expression of PRL and its receptor (PRLR) were characterised during sea bream
      embryonic and larval development, by semi-quantitative and quantitative RT-PCR,
      respectively, until 46 days post-hatch (DPH). Immunocytochemistry with antisera
      specific for sea bream PRLR was carried out with larval sections from hatching up
      to 46 DPH. A single transcript of PRL (1.35 Kb) and PRLR (2.8 Kb) identical to
      the transcripts previously characterised in adult tissue, are present in sea
      bream embryos and larvae. PRL expression is first detectable at neurula and in
      all samples collected thereafter. The lowest levels of PRL mRNA are detected in
      sea bream embryos up until neurula when expression starts to increase. The
      maximal levels of PRL expression were detected at 24 DPH. PRLR transcripts first
      appear at 12h post-fertilisation (0.002 rho mol/microg total larvae RNA)
      (blastula) and increase significantly during gastrulation (0.245 rho mol/microg
      total larvae RNA) reaching a maximum at 2 DPH (0.281 rho mol/microg total larvae
      RNA). After hatching a significant reduction in PRLR expression is observed which
      reaches a minimum at 4 DPH (0.103 rho mol/microg total larvae RNA), gradually
      increasing thereafter. Immunocytochemistry revealed the presence of PRLR in early
      post-hatching stages of larvae in tissues derived from all three germ layers.

PMID- 12812780
TI  - Clarification of emu serum for peptide hormone assay using polyethylene glycol
      precipitation.
AB  - Interference in radioimmunoassays (RIAs) was frequently encountered during
      endocrinological studies of the emu (Dromaius novaehollandiae). Interference was
      greatest when serum was cloudy or opaque. Such samples appeared seasonally, in
      spring and summer during the phase of fat deposition, and in the winter when
      females were laying. These poor quality samples did not allow accurate
      measurement by RIAs of several peptide hormones for a full year. To prepare them
      for assay, these sera were clarified using a polyethylene glycol (PEG) solution
      at a final concentration of 7.5%. This treatment was effective in most cases.
      After treatment with the PEG, recoveries of LH, glucagon, and prolactin were
      greater than 75% and that for insulin was 40%. Regardless of the level of
      recovery, there was a high correlation of assay results between non-opaque native
      and PEG-treated sera. Serum samples containing large amounts of interfering high
      molecular weight components, such as lipoproteins, can be clarified with PEG,
      enabling their accurate measurement by RIA.

PMID- 12812781
TI  - Characterization of thyroid hormone receptor alpha and beta in the metamorphosing
      Japanese conger eel, Conger myriaster.
AB  - Two distinct TR alpha cDNA clones (TR alpha A and TR alpha B) were isolated from
      conger eel (Conger myriaster). The deduced amino acid sequences of the conger eel
      TR alphas showed higher homologies to the TR alphas of other vertebrates than to
      TR betas. Determination of TR mRNA in metamorphosing eels was performed using
      competitive RT-PCR. Of the two TR alpha mRNAs identified, TR alpha A mRNA
      expression was shown to be relatively higher than that of TR alpha B, and there
      was a peak in the expression of each during metamorphic climax. We hypothesize
      that both TR alphas play important roles in morphological differentiation during
      metamorphosis. The expression pattern of TR beta 1 mRNA was also higher during
      metamorphic climax and high levels of expression continued after metamorphosis.
      This suggests that TR beta 1 is the adult fish form which appears at high
      frequency after metamorphosis. It was also shown that TR beta 2 is highly
      expressed specifically in the brain and pituitary gland in larvae and juvenile
      forms including during metamorphosis and there was a peak in TR beta 2 mRNA in
      the elver after metamorphosis. Thus, we propose that TR beta 2 plays an important
      role in the regulation of the hypothalamic-pituitary-thyroid axis.

PMID- 12812782
TI  - Cloning of cDNAs encoding the three pituitary glycoprotein hormone beta subunit
      precursor molecules in the Japanese toad, Bufo japonicus.
AB  - Complementary DNAs encoding precursor molecules of the beta subunits of three
      pituitary glycoprotein hormones (LH, FSH, and TSH) of the Japanese toad (Bufo
      japonicus) were isolated and sequenced. Unexpectedly large numbers of single
      nucleotide substitutions were found in all three beta subunit cDNAs. The eight
      isolated LH beta precursor cDNA clones were classified into six forms of
      nucleotide sequence, with four nucleotide substitutions each in the apoprotein
      coding region and in the 3' untranslated region (UTR). In the deduced amino acid
      sequence, the LH beta subunit showed two forms with a single amino acid
      substitution. The seven isolated FSH beta subunit cDNAs were classified into two
      forms, which differed from each other at 11 positions in the 3' UTR. The six
      isolated TSH beta subunit clones were classified into four forms with 2 and 5
      nucleotide substitutions in the signal peptide and apoprotein coding regions,
      respectively. However, all the substitutions in the apoprotein coding region were
      silent. The substitution in the signal peptide coding region could produce three
      forms of signal peptide. Amino acid sequence comparison revealed that the toad LH
      beta subunit is more similar to the fish GTH II beta subunit than to mammalian
      and avian LH beta subunits. We found that the toad LH beta subunit molecule is a
      partial chimera of LH and FSH; amino acid residues located in 36th to 42nd and
      96th to 99th are identical or similar to those of not LH- but FSH-beta subunit in
      mammalian, whereas it is more similar to LH- than FSH-beta subunit in total. We
      also found that the toad FSH beta subunit is more similar to the fish GTH II beta
      subunit than to the fish GTH I beta subunit and that the toad TSH beta subunit is
      more similar to tetrapod TSH beta subunits than to fish TSH beta subunits.

PMID- 12812783
TI  - Coordinate regulation of small temporal RNAs at the onset of Drosophila
      metamorphosis.
AB  - The lin-4 and let-7 small temporal RNAs play a central role in controlling the
      timing of Caenorhabditis elegans cell fate decisions. let-7 has been conserved
      through evolution, and its expression correlates with adult development in
      bilateral animals, including Drosophila [Nature 408 (2000), 86]. The best match
      for lin-4 in Drosophila, miR-125, is also expressed during pupal and adult stages
      of Drosophila development [Curr. Biol. 12 (2002), 735]. Here, we ask whether the
      steroid hormone ecdysone induces let-7 or miR-125 expression at the onset of
      metamorphosis, attempting to link a known temporal regulator in Drosophila with
      the heterochronic pathway defined in C. elegans. We find that let-7 and miR-125
      are coordinately expressed in late larvae and prepupae, in synchrony with the
      high titer ecdysone pulses that initiate metamorphosis. Unexpectedly, however,
      their expression is neither dependent on the EcR ecdysone receptor nor inducible
      by ecdysone in cultured larval organs. Although let-7 and miR-125 can be induced
      by ecdysone in Kc tissue culture cells, their expression is significantly delayed
      relative to that seen in the animal. let-7 and miR-125 are encoded adjacent to
      one another in the genome, and their induction correlates with the transient
      appearance of an approximately 500-nt RNA transcribed from this region, providing
      a mechanism to explain their precise coordinate regulation. We conclude that a
      common precursor RNA containing both let-7 and miR-125 is induced independently
      of ecdysone in Drosophila, raising the possibility of a temporal signal that is
      distinct from the well-characterized ecdysone-EcR pathway.

PMID- 12812784
TI  - Temporal regulation of microRNA expression in Drosophila melanogaster mediated by
      hormonal signals and broad-Complex gene activity.
AB  - lin-4 and let-7 are founding members of an extensive family of genes that produce
      small transcripts, termed microRNAs (miRNAs). In Caenorhabditis elegans, lin-4
      and let-7 control the timing of postembryonic events by translational repression
      of target genes, permitting progression from early to late developmental
      programs. To identify Drosophila melanogaster miRNAs that could play similar
      roles in the control of developmental timing, we characterized the developmental
      expression profile of 24 miRNAs in Drosophila, and found 7 miRNAs that are either
      upregulated or downregulated in conjunction with metamorphosis. The upregulation
      of three of these miRNAs (mir-100, mir-125, and let-7), and the downregulation of
      a fourth (mir-34) requires the hormone ecdysone (Ecd) and the activity of the Ecd
      inducible gene Broad-Complex. Interestingly, mir-125 is a putative homologue of
      lin-4. mir-100, -125, and let-7 are clustered within an 800-bp region on
      chromosome 2L, suggesting that these three miRNAs may be coordinately regulated
      via common cis-acting elements during metamorphosis. In S2 cells, Ecd and the
      juvenile hormone analog methoprene exert opposite effects on the expression of
      these four miRNAs, indicating the participation of both these hormones in the
      temporal regulation of mir-34, -100, -125, and let-7 expression in vivo.

PMID- 12812785
TI  - Sox10 regulates the development of neural crest-derived melanocytes in Xenopus.
AB  - The transcription factors of the Sox family play important roles in diverse
      developmental processes. A number of genetic studies have established that Sox10
      is a major regulator of neural crest formation. Here, we report the cloning and
      functional analysis of the Xenopus Sox10 gene. Sox10 mRNA accumulates during
      gastrulation at the lateral edges of the neural plate, in the neural crest
      forming region. In this tissue, Sox10 expression is regulated by Wnt signaling
      and colocalizes with two major regulators of neural crest formation, Slug and
      Sox9. While initially expressed in neural crest cells from all axial levels, at
      the tailbud stage, Sox10 is downregulated in the cranial neural crest and
      persists mostly in neural crest cells from the trunk region. Overexpression of
      Sox10 causes a dramatic expansion of the Slug expression domain. We show that the
      C-terminal portion of Sox10 is sufficient to mediate this activity. Later during
      embryogenesis, Sox10-injected embryos show a massive increase in pigment cells
      (Trp-2-expressing cells). The responsiveness of the embryo to Sox10
      overexpression by expansion of the Slug expression domain and ectopic production
      of Trp-2-positive cells and differentiated melanocytes is lost during
      gastrulation, as revealed by a hormone-inducible Sox10 construct. These results
      suggest that Sox10 is involved in the specification of neural crest progenitors
      fated to form the pigment cell lineage.

PMID- 12812786
TI  - DLX5 positions the neural crest and preplacode region at the border of the neural
      plate.
AB  - The neural crest and sensory placodes arise from a region of the embryonic
      ectoderm that lies between the neural plate and future epidermis. While some of
      the signalling pathways that are involved in cell fate determination at the
      border of the neural plate have been characterised, it is still unclear how
      different signals are integrated. Transcription factors of the DLX gene family
      that may mediate such cell fate decisions are expressed at the border of the
      neural plate. Here, we demonstrate that DLX5 is involved in positioning this
      border by repressing neural properties and simultaneously by promoting the
      formation of border-like cells that express the neural fold markers MSX1 and BMP4
      and the preplacodal region marker SIX4. However, DLX5 is not sufficient to impart
      epidermal character or to specify cell fates that arise at the border of the
      neural plate, like neural crest or fully formed sensory placodes, in a cell
      autonomous manner. Additional signals are generated when mature neural plate and
      epidermis interact and these are required for neural crest formation. We propose
      that patterning of the embryonic ectoderm is a multistep process that
      sequentially subdivides the ectoderm into regions with defined cell fates.

PMID- 12812787
TI  - A role for Wnt/beta-catenin signaling in lens epithelial differentiation.
AB  - The differentiation of epithelial cells and fiber cells from the anterior and
      posterior compartments of the lens vesicle, respectively, give the mammalian lens
      its distinctive polarity. While much progress has been made in understanding the
      molecular basis of fiber differentiation, little is known about factors that
      govern the differentiation of the epithelium. Members of the Wnt growth factor
      family appear to be key regulators of epithelial differentiation in various organ
      systems. Wnts are ligands for Frizzled receptors and can activate several
      signaling pathways, of which the best understood is the Wnt/beta-catenin pathway.
      The presence of LDL-related protein coreceptors (LRPs) 5 or 6 has been shown to
      be a requirement for Wnt signaling through the beta-catenin pathway. To access
      the role of this signaling pathway in the lens, we analyzed mice with a null
      mutation of lrp6. These mice had small eyes and aberrant lenses, characterized by
      an incompletely formed anterior epithelium resulting in extrusion of the lens
      fibers into the overlying corneal stroma. We also showed that multiple Wnts,
      including 5a, 5b, 7a, 7b, 8a, 8b, and Frizzled receptors 1, 2, 3, 4, and 6, were
      detected in the lens. Expression of these molecules was generally present
      throughout the lens epithelium and extended into the transitional zone, where
      early fiber elongation occurs. In addition to both LRP5 and LRP6, we also showed
      the expression of other molecules involved in Wnt signaling and its regulation,
      including Dishevelleds, Dickkopfs, and secreted Frizzled-related proteins. Taken
      together, these results indicate a role for Wnt signaling in regulating the
      differentiation and behavior of lens cells.

PMID- 12812788
TI  - An increase in surface area is not required for cell division in early sea urchin
      development.
AB  - Cell division requires an increase in surface area to volume ratio. During early
      development, surface area can increase, volume can decrease, or surface
      topography can be optimized to allow for division. While exocytosis is thought to
      be essential for division [Mol. Biol. Cell 10 (1999), 2735; Proc. Natl. Acad.
      Sci. USA 99 (2002), 3633], exocytosis doesn't always yield an increase in surface
      area [Proc. Natl. Acad. Sci. USA 79 (1982), 6712]. We used multiphoton laser
      scanning microscopy, fluorescence spectroscopy, and electron microscopy to
      monitor membrane trafficking, surface area, volume, and surface topography during
      early sea urchin development. Despite extensive membrane trafficking monitored by
      FM 1-43 fluorescence, we find that the net surface area of the embryo does not
      change prior to the eight-cell stage. During this period, embryo volume decreases
      by 15%, and microvilli disappear from interior facing membrane segments. Thus,
      the first three cell divisions utilize residual membrane liberated by decreasing
      cytoplasmic volume, and reducing microvilli density on interior facing membranes.
      Only after the eight-cell stage was a net increase in FM 1-43 fluorescence from
      the embryo surface detected. Our data suggest that compensatory endocytosis is
      downregulated after this developmental stage to yield an increase in surface area
      for cell division.

PMID- 12812789
TI  - Nifedipine reveals the existence of two discrete components of the progesterone
      induced [Ca2+]i transient in human spermatozoa.
AB  - The steroid progesterone, an agonist of acrosome reaction, induces a biphasic
      [Ca(2+)](i)-signal in human sperm comprising an initial transient [Ca(2+)](i)
      elevation, and a subsequent ramp or plateau. Nifedipine, an inhibitor of voltage
      operated Ca(2+) channels, inhibits progesterone-induced acrosome reaction in
      human sperm, but fluorimetric studies have detected no effect of this compound on
      the progesterone-induced [Ca(2+)](i) signal. We have used single-cell imaging to
      study the effects of nifedipine on [Ca(2+)](i) signalling in human sperm.
      Analysis of mean responses from large numbers of cells showed that treatment with
      nifedipine reduced the duration but not the amplitude of the progesterone-induced
      [Ca(2+)](i) transient. In control cells, the latency of the transient peak
      (maximum fluorescence) fell within the range of 30-105 s. In the presence of
      nifedipine, very few cells peaked "late" (>60 s after application of
      progesterone). Analysis of transient responses in control cells revealed
      characteristic "early" and "late" responses, most cells showing both "early" and
      "late" transients, whereas "late" transients were rare and smaller in the
      presence of nifedipine. Sustained responses showed strong association with late
      transients, and occurrence and amplitude of sustained responses were
      significantly reduced in nifedipine pretreated cells. These findings are
      consistent with the occurrence of a discrete, nifedipine-sensitive component of
      the progesterone-induced [Ca(2+)](i) transient that peaks 1-2 min after exposure
      to the hormone and is crucial for the induction of the sustained [Ca(2+)](i)
      signal.

PMID- 12812790
TI  - Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal
      development of secondary palate.
AB  - The forkhead genes encode a transcription factor involved in embryogenesis and
      pattern formation in multicellular organisms. They are mammalian transcriptional
      regulators that bind DNA as a monomer through their forkhead domain. The Foxf2
      (LUN) mRNA is expressed in the mesenchyme directly adjacent to the ectoderm
      derived epithelium in the developing tongue and in the mesenchyme adjacent to the
      endoderm-derived epithelium in the gastrointestinal (GI) tract, lungs, and
      genitalia. To investigate the developmental role of the Foxf2 gene during
      embryogenesis, we disrupted the Foxf2 gene and showed that these mutant mice died
      shortly after birth. Mice lacking the Foxf2 gene were found to develop cleft
      palate and an abnormal tongue. In addition, we found that the GI tract and the
      lungs of Foxf2-deficient newborn mice were normal in both morphology and
      function. These results suggest that the Foxf2 gene plays key roles in
      palatogenesis by reshaping the growing tongue.

PMID- 12812791
TI  - Zebrafish N-cadherin, encoded by the glass onion locus, plays an essential role
      in retinal patterning.
AB  - Genetic screens in zebrafish identified several loci that play essential roles in
      the patterning of retinal architecture. Here, we show that one of them, glass
      onion, encodes the N-cadherin gene. The glo(m117) mutant allele contains a
      substitution of the Trp2 residue known for its essential role in the adhesive
      properties of classic cadherins. Both the glo(m117) and pac(tm101b) mutant N
      cadherin alleles affect the polarity of the retinal neuroepithelial sheet and,
      unexpectedly, both result in cell-nonautonomous phenotypes in retinal patterning.
      The late onset of mutant N-cadherin phenotypes may be due to the ability of
      classic cadherins to substitute each other's function.

PMID- 12812792
TI  - Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate.
AB  - During embryonic development, organs arise along the gut tube as a series of buds
      in a stereotyped anterior-posterior (A-P) pattern. Using chick-quail chimeras and
      in vitro tissue recombination, we studied the interactions governing the
      induction and maintenance of endodermal organ identify focusing on the pancreas.
      Though several permissive signals in pancreatic development have been previously
      identified, here we provide evidence that lateral plate mesoderm sends
      instructive signals to the endoderm, signals that induce expression of the
      pancreatic genes Pdx1, p48, Nkx6.1, glucagon, and insulin. Moreover, this
      instructive signal directs cells to form ectopic insulin-positive islet-like
      clusters in endoderm that would otherwise form more rostral organs. Once
      generated, endocrine cells no longer require interaction with mesoderm, but
      nonendocrine cells continue to require permissive signals from the mesoderm.
      Stimulation of activin, BMP, or retinoic acid signaling is sufficient to induce
      Pdx1 expression in endoderm anterior to the pancreas. Lateral plate mesoderm
      appears to pattern the endoderm in a posterior-dominant fashion as first noted in
      the patterning of the neural tube at the same embryonic stage. These findings
      argue for a central role of the mesoderm in coordinating the A-P pattern of all
      three primary germ layers.

PMID- 12812793
TI  - Stimulation of ectodermal organ development by Ectodysplasin-A1.
AB  - Organs developing as ectodermal appendages share similar early morphogenesis and
      molecular mechanisms. Ectodysplasin, a signaling molecule belonging to the tumor
      necrosis factor family, and its receptor Edar are required for normal development
      of several ectodermal organs in humans and mice. We have overexpressed two splice
      forms of ectodysplasin, Eda-A1 and Eda-A2, binding to Edar and another TNF
      receptor, Xedar, respectively, under the keratin 14 (K14) promoter in the
      ectoderm of transgenic mice. Eda-A2 overexpression did not cause a detectable
      phenotype. On the contrary, overexpression of Eda-A1 resulted in alterations in a
      variety of ectodermal organs, most notably in extra organs. Hair development was
      initiated continuously from E14 until birth, and in addition, the transgenic mice
      had supernumerary teeth and mammary glands, phenotypes not reported previously in
      transgenic mice. Also, hair composition and structure was abnormal, and the
      cycling of hairs was altered so that the growth phase (anagen) was prolonged.
      Both hairs and nails grew longer than normal. Molar teeth were of abnormal shape,
      and enamel formation was severely disturbed in incisors. Furthermore, sweat gland
      function was stimulated and sebaceous glands were enlarged. We conclude that
      ectodysplasin-Edar signaling has several roles in ectodermal organ development
      controlling their initiation, as well as morphogenesis and differentiation.

PMID- 12812794
TI  - Expression of the C. elegans labial orthologue ceh-13 during male tail
      morphogenesis.
AB  - Hox genes are transcriptional regulators of metazoan body regionalization along
      the anteroposterior axis that act by specifying positional identity in
      differentiating cells. ceh-13, the labial orthologue in Caenorhabditis elegans,
      is expressed both during embryogenesis and post- embryonic development. Using GFP
      reporter analysis and immunocytochemistry, we discovered a spatiotemporal pattern
      of gene expression in the male tail during the L3 and L4 larval stages that is
      TGF-beta pathway-dependent. Analysis of reporter activity in transgenic animals
      identified a distinct promoter region driving male tail-specific ceh-13
      expression. We also report the interspecies conservation of sequence motifs
      within this region and speculate that, in the course of evolutionary
      diversification, ceh-13 may have acquired new functionality while conserving its
      homeotic role.

PMID- 12812796
TI  - The endothelin receptor-B is required for the migration of neural crest-derived
      melanocyte and enteric neuron precursors.
AB  - Mutations in the genes encoding endothelin receptor-B (Ednrb) and its ligand
      endothelin-3 (Edn3) affect the development of two neural crest-derived cell
      types, melanocytes and enteric neurons. EDNRB signaling is exclusively required
      between E10.5 and E12.5 during the migratory phase of melanoblast and enteric
      neuroblast development. To determine the fate of Ednrb-expressing cells during
      this critical period, we generated a strain of mice with the bacterial beta
      galactosidase (lacZ) gene inserted downstream of the endogenous Ednrb promoter.
      The expression of the lacZ gene was detected in melanoblasts and precursors of
      the enteric neuron system (ENS), as well as other neural crest cells and
      nonneural crest-derived lineages. By comparing Ednrb(lacZ)/+ and
      Ednrb(lacZ)/Ednrb(lacZ) embryos, we determined that the Ednrb pathway is not
      required for the initial specification and dispersal of melanoblasts and ENS
      precursors from the neural crest progenitors. Rather, the EDNRB-mediated
      signaling is required for the terminal migration of melanoblasts and ENS
      precursors, and this pathway is not required for the survival of the migratory
      cells.

PMID- 12812795
TI  - Differential requirement for Gli2 and Gli3 in ventral neural cell fate
      specification.
AB  - Sonic hedgehog (Shh) directs the development of ventral cell fates, including
      floor plate and V3 interneurons, in the mouse neural tube. Here, we show that the
      transcription factors Gli2 and Gli3, mediators of Shh signaling, are required for
      the development of the ventral cell fates but make distinct contributions to
      controlling cell fates at different locations along the rostral-caudal axis.
      Mutants lacking Patched1 (Ptc1), the putative receptor of Shh, were used to
      analyze Gli functions. Ptc1(-/-) mutants develop floor plate, motor neuron, and
      V3 interneuron progenitors in lateral and dorsal regions, suggesting that the
      normal role of Ptc1 is to suppress ventral cell development in dorsal neural
      tube. The Ptc1(-/-) phenotype is rescued, with restoration of dorsal cell types,
      by the lack of Gli2, but only in the caudal neural tube. In triple mutants of
      Gli2, Gli3, and Ptc1, dorsal and lateral cell fates are restored in the entire
      neural tube. These observations suggest that Gli2 is essential for ventral
      specification in the caudal neural tube, and that in more rostral regions, only
      Gli3 can promote development of ventral cells if Gli2 is absent. Thus, Shh
      signaling is mediated by overlapping but distinct functions of Gli2 and Gli3, and
      their relative contributions vary along the rostral-caudal axis.

PMID- 12812797
TI  - The human tissue plasminogen activator-Cre mouse: a new tool for targeting
      specifically neural crest cells and their derivatives in vivo.
AB  - The ontogeny of neural crest cells (NCC) involves a number of orchestrated
      variety of derivatives, including components of the peripheral nervous system and
      melanocytes. Thus, it represents an excellent model system to investigate
      mechanisms controlling epithelial-mesenchymal transitions, cell migration and
      differentiation, as well as cell proliferation and death. We have established a
      new transgenic line expressing the Cre recombinase under the control of the human
      tissue plasminogen activator promoter (Ht-PA). The activity of the reporter in
      the Ht-PA-Cre/R26R embryos is observed as early as Theiler stage 12 in the
      cephalic mesenchyme. Later, the targeted cells include all the known derivatives
      of cranial, vagal, and trunk NCC, including craniofacial structures and cranial
      ganglia, cardiac and endocrine derivatives, melanocytes, peripheral, and enteric
      nervous system. At the vagal level, the location of presumptive enteric NCC
      differs from their avian counterparts in their ability to invade the mesenchyme
      lateral to the neural tube. In contrast to the Wnt1-Cre line, the Ht-PA-Cre line
      does not target the central nervous system and therefore renders it more specific
      for NCC. Our Ht-PA-Cre mice represent a novel model to specifically target
      conditional mutations in migratory NCC.

PMID- 12812799
TI  - At the interface of the affective, behavioral, and cognitive neurosciences:
      decoding the emotional feelings of the brain.
AB  - This article summarizes recent conceptual and empirical advances in understanding
      basic affective processes of hte mammalian brain and how we might distinguish
      affective from cognitive processes. Six reasons are advanced for distinguishing
      the two types of consciousness, including (i) the presence of experienced
      valence, (ii) cortical sub-cortical locus of control, (iii) different
      developmental trajectories, (iv) informational vs organic considerations, (v)
      differences in bodily expressions, (vi) differences in cerebral laterality. The
      position is advanced that to make progress on understanding the neurobiological
      nature of affect, we need to utilize experimental strategies different from those
      that are common in cognitive science.

PMID- 12812800
TI  - Demythologizing the emotions: adaptation, cognition, and visceral representations
      of emotion in the nervous system.
AB  - This article highlights four issues about the neurobiology of emotions:
      adaptation vs. dysfunction, peripheral and central representations of emotion,
      the regulation of the internal milieu, and whether emotions are cognitive. It is
      argued that the emotions evolved to play diverse adaptive roles and are
      biologically vital sources of information processing. They were not designed as
      pieces of pathology, though they certainly can underlie some psychophathologies.
      Emotions are, in part, appraisal systems that are operative at numerous level of
      the nervous system from the brainstem to the cortex. Like other information
      processing systems they are not perfect cognitive systems. Emotional systems
      often utilize somatic and visceral information for appraisals of events to
      facilitate decisions of whether to approach or avoid objects. The neural systems
      of emotions traverse the entire neural axis and are linked to the regulation of
      the internal milieu. Thus, in addition to the experiential aspects of emotions,
      emotions embody appraisal systems that are pervasive to all levels of the brain
      to facilitate function, adaptation, and survival.

PMID- 12812801
TI  - Neuroanatomy of the human affective system.
AB  - We provide a brief overview of the structures associated with the limbic system
      using fixed human material. Although the review is by no means intended to be
      exhaustive, its purpose is to provide a tutorial on the primary structures that
      are involved in the experience, expression, and regulation of emotion and their
      anatomical location so that the reader can use this as a "pedagogical guide" for
      orientation and understanding of the many papers that appear in this Special
      Issue.

PMID- 12812802
TI  - Development of frontal electroencephalogram (EEG) and heart rate (ECG) responses
      to affective musical stimuli during the first 12 months of post-natal life.
AB  - We examined the development of infants' regional electrocortical (EEG) and heart
      rate (ECG) responses to affective musical stimuli during the first 12 months of
      post-natal life. Separate groups of infants were seen at 3 (n=33), 6 (n=42), 9
      (n=52), and 12 (n=40) months of age at which time regional EEG and ECG responses
      were continuously recorded during a baseline condition and during the
      presentation of three orchestral pieces that were known to vary in affective
      valence and intensity (happy, sad, fear). Overall, there were two important
      findings. First, we found that although the overall amount of EEG 4-8 Hz power
      increased between 3 and 12 months, the distribution of EEG power changed across
      age, with the younger infants (3- and 6-month-olds) showing no difference between
      frontal and parietal regions, but the older infants (9- and 12-month-olds)
      showing relatively more activation at frontal than at parietal sites. This
      development likely reflects the maturation of frontal lobe function. Second, we
      found that the presentation of affective music significantly increased brain
      activity at 3 months of age, had seemingly little effect at 6 and 9 months, and
      significantly attenuated brain activity at 12 months. Findings suggest that there
      is a clear developmental change in the effect of music on brain activity in the
      first year, with music having a "calming" influence on infants by the end of the
      first year of life.

PMID- 12812803
TI  - Individual differences in children's performance during an emotional Stroop task:
      a behavioral and electrophysiological study.
AB  - Two studies using the emotional Stroop with 11-year-old children were completed.
      In Study 1, children were assigned to either the "interference group" or the
      "facilitation group" based on their performance on the task. The interference
      group was slower to respond to emotion words (positive and negative) versus
      control words. The facilitation group was faster to respond to the emotion words.
      The groups were then compared on a set of cognitive, emotional, and social
      measures collected at ages 4, 7, and 11. The interference group showed greater
      signs of emotional and social, but not cognitive, maladjustment across time.
      Study 2 replicated the findings of Study 1. In addition, event-related potentials
      (ERPs) were collected in Study 2. The ERP data replicated earlier traditional
      Stroop studies. In addition, positive and negative words showed differences in
      processing across components. In particular, negative words appeared to tax
      attentional and processing resources more than positive words.

PMID- 12812804
TI  - Facial expressions of emotion: a cognitive neuroscience perspective.
AB  - Facial expressions are one example of emotional behavior that illustrate the
      importance of emotions to both basic survival and social interaction. Basic
      facial responses to stimuli such as sweet and bitter taste are important for
      species fitness and governed by simple rules. Even at this basic level, facial
      responses have communicative value to other species members. During evolution
      simple facial responses were extended for use in more complex nonverbal
      communications; the responses are labile. The perception and production of facial
      expressions are cognitive processes and numerous subcortical and cortical areas
      contribute to these operations. We suggest that no specific emotion center exists
      over and above cognitive systems in the brain, and that emotion should not be
      divorced from cognition.

PMID- 12812805
TI  - Dissociable neural systems for recognizing emotions.
AB  - This study tested the hypothesis that the recognition of emotions would draw upon
      anatomically separable brain regions, depending on whether the stimuli were
      static or explicitly conveyed information regarding actions. We investigated the
      hypothesis in a rare subject with extensive bilateral brain lesions, patient B.,
      by administering tasks that assessed recognition and naming of emotions from
      visual and verbal stimuli, some of which depicted actions and some of which did
      not. B. could not recognize any primary emotion other than happiness, when
      emotions were shown as static images or given as single verbal labels. By
      contrast, with the notable exception of disgust, he correctly recognized primary
      emotions from dynamic displays of facial expressions as well as from stories that
      described actions. Our findings are consistent with the idea that information
      about actions is processed in occipitoparietal and dorsal frontal cortices, all
      of which are intact in B.'s brain. Such information subsequently would be linked
      to knowledge about emotions that depends on structures mapping somatic states,
      many of which are also intact in B.'s brain. However, one of these somatosensory
      structures, the insula, is bilaterally damaged, perhaps accounting for B.'s
      uniformly impaired recognition of disgust (from both static and action stimuli).
      Other structures that are damaged in B.'s brain, including bilateral inferior and
      anterior temporal lobe and medial frontal cortices, appear to be critical for
      linking perception of static stimuli to recognition of emotions. Thus the
      retrieval of knowledge regarding emotions draws upon widely distributed and
      partly distinct sets of neural structures, depending on the attributes of the
      stimulus.

PMID- 12812806
TI  - Cerebral blood flow and anxiety in older men: an analysis of resting anterior
      asymmetry and prefrontal regions.
AB  - Asymmetric resting blood flow in prefrontal and hemispheric regions, assessed by
      single photon emission computed tomography (SPECT), was examined as a potential
      biological marker for enhanced trait and state anxiety in 30 older men (ages 55
      81). Average and asymmetric perfusion in dorsolateral, medial, and orbital
      regions of the prefrontal lobes was also assessed. Results indicated a
      significant association between lower levels of resting dorsolateral blood flow
      and greater state anxiety responses to a series of stressful provocations
      (measured on a separate occasion). A significant curvilinear (U-shaped) relation
      between asymmetric dorsolateral perfusion and state anxiety was also identified;
      increased asymmetric blood flow favoring either the right or the left
      dorsolateral region related to higher levels of state anxiety. However, this
      association was attenuated by age and systolic blood pressure. Resting perfusion
      in the dorsolateral region may represent a more reliable biological marker for
      state anxiety than trait anxiety in older men.

PMID- 12812807
TI  - Central and autonomic nervous system integration in emotion.
AB  - Emotions involve physiological responses that are regulated by the brain. The
      present paper reviews the empirical literature on central nervous system (CNS)
      and autonomic nervous system (ANS) concomitants of emotional states, with a focus
      on studies that simultaneously assessed CNS and ANS activity. The reviewed data
      support two primary conclusions: (1) numerous cortical and subcortical regions
      show co-occurring activity with ANS responses in emotion, and (2) there may be
      reversed asymmetries on cortical and subcortical levels with respect to CNS/ANS
      interrelations. These observations are interpreted in terms of a model of
      neurovisceral integration in emotion, and directions for future research are
      presented.

PMID- 12812808
TI  - Heart rate and respiration in reptiles: contrasts between a sit-and-wait predator
      and an intensive forager.
AB  - The current study investigated respiration and heart rate in two species of
      reptiles with distinct behavioral strategies: (1) the Sudan plated lizard
      (Gerrhosaurus major), a sit-and-wait predator; and (2) the Savanna monitor
      (Varanus exanthematicus), an intensive forager. It was hypothesized that (a) the
      plated lizard would not express respiratory sinus arrhythmia, and (b) the
      monitor, a reptile with behavioral and physiological characteristics similar to
      mammals, might express respiratory sinus arrhythmia, a pattern previously
      observed only in mammals. The data demonstrated that although there were strong
      vagal influences on the heart, respiratory activity was not manifested in the
      heart rate pattern of the plated lizards. In contrast, the monitor exhibited a
      reliable ventilatory influence on the heart rate pattern, although the pattern
      differed from the respiratory sinus arrhythmia observed in mammals. Consistent
      with the Polyvagal Theory (), the vagal control of the reptilian heart in both
      species appears to be mediated through the phylogenetically older unmyelinated
      system, a system that evolved to support metabolic conservation and not social
      behavior.

PMID- 12812809
TI  - Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and
      beneficial effects of play therapy.
AB  - It has been recently shown that human adolescents with Attention
      Deficit/Hyperactivity Disorder (ADHD) have frontal lobe deficits, especially on
      the right sides of their brains (). ADHD is commonly treated with
      psychostimulants which may have adverse consequences. Hence, less invasive
      therapies need to be developed. In the present work, we tested the ability of
      right frontal lesions to induce hyperactivity in rats. We also evaluated the
      effects of chronic play therapy during early adolescence to reduce both
      hyperactivity and the elevated playfulness later in development. Play therapy was
      able to reduce both hyperactivity and excessive playfulness. In additional work,
      we found that access to rough-and-tumble play in normal animals could enhance
      subsequent behavioral indices of behavioral inhibition (i.e., freezing in
      response to a startle stimulus) that appeared to be independent of increased
      fearfulness and fatigue. Overall, these results suggest that (1) neonatal frontal
      lobe lesions can be used as an animal model of the overactivity in ADHD and (2)
      rough-and-tumble play therapy may be a new useful treatment for ADHD.

PMID- 12812810
TI  - Pleasures of the brain.
AB  - How does the brain cause positive affective reactions to sensory pleasure? An
      answer to pleasure causation requires knowing not only which brain systems are
      activated by pleasant stimuli, but also which systems actually cause their
      positive affective properties. This paper focuses on brain causation of
      behavioral positive affective reactions to pleasant sensations, such as sweet
      tastes. Its goal is to understand how brain systems generate 'liking,' the core
      process that underlies sensory pleasure and causes positive affective reactions.
      Evidence suggests activity in a subcortical network involving portions of the
      nucleus accumbens shell, ventral pallidum, and brainstem causes 'liking' and
      positive affective reactions to sweet tastes. Lesions of ventral pallidum also
      impair normal sensory pleasure. Recent findings regarding this subcortical
      network's causation of core 'liking' reactions help clarify how the essence of a
      pleasure gloss gets added to mere sensation. The same subcortical 'liking'
      network, via connection to brain systems involved in explicit cognitive
      representations, may also in turn cause conscious experiences of sensory
      pleasure.

PMID- 12812811
TI  - Seven sins in the study of emotion: correctives from affective neuroscience.
AB  - This brief commentary highlights seven sins in the study of emotion that are
      explicitly treated in contemporary affective neuroscience. These sins are (1)
      Affect and cognition are subserved by separate and independent neural circuits;
      (2) Affect is subcortical; (3) Emotions are in the head; (4) Emotions can be
      studied from a purely psychological perspective; (5) Emotions are similar in
      structure across age and species; (6) Specific emotions are instantiated in
      discrete locations in the brain; and (7) Emotions are conscious feeling states.
      Each of these is briefly discussed and evidence from affective neuroscience that
      bears on these sins is noted. The articles in this Special Issue underscore the
      vitality of research in affective neuroscience and illustrate how some of these
      sins can be addressed and rectified using concepts and methods from affective
      neuroscience.

PMID- 12812812
TI  - Defining clinically meaningful change in health-related quality of life.
AB  - This article reviews current approaches to defining clinically meaningful change
      in health-related quality of life (HRQOL) and provides guidelines for their use.
      Definitions of clinically meaningful change are discussed. Two broad methods for
      identifying clinically meaningful change are contrasted: anchor-based methods and
      distribution-based methods. Anchor-based methods include cross-sectional
      approaches and longitudinal approaches. Distribution-based methods include those
      based on statistical significance, sample variability, and measurement precision.
      Anchor-based and distribution-based methods have advantages and limitations, and
      neither seems to be superior to the other. An integrated system for defining
      clinically meaningful change is recommended that combines anchor-based and
      distribution-based methods. We propose a new terminology for describing
      meaningful change derived from anchor-based and distribution-based methods.

PMID- 12812813
TI  - Late-starter sites in randomized controlled trials.
AB  - In a cohort of 14 randomized controlled trials conducted by the Adult AIDS
      Clinical Trials Group between 1986 and 1999 with a target sample size of >400
      (total enrollment 15,531 patients), we evaluated whether "late-starter" sites can
      make a meaningful contribution to eventual trial accrual. The sites that started
      recruiting within 5 months from the time the first patient entered the trial were
      eventually responsible for over 90% of the total enrollment in 11 of the 14
      trials. Across the 14 trials, some sites were consistently among the first to
      start enrollment, whereas others were routinely among the last. The late-starter
      sites are unlikely to make important contributions to eventual trial enrollment
      in large clinical trials conducted by groups with a fixed number of sites.
      Protracting administrative efforts to add more sites many months after a
      multicenter trial has started may not be useful to trial accrual.

PMID- 12812814
TI  - Adequacy of reporting race/ethnicity in clinical trials in areas of health
      disparities.
AB  - Although federal initiatives have mandated broader inclusion of minorities in
      clinical research on diseases that have disparities in health by race and
      ethnicity, it is not clear whether these initiatives have affected reporting of
      trial results. The objective of this study was to examine the reporting of
      race/ethnicity in clinical trials reports in areas of known disparities in health
      (i.e., diabetes, cardiovascular disease, HIV/AIDS, and cancer) and to determine
      what factors were associated with reporting of race/ethnicity in results. We
      performed a Medline search covering the period January 1989 to Oct 2000 to
      identify clinical trials of diabetes, cardiovascular disease, HIV/AIDS, and
      cancer published in the Annals of Internal Medicine, JAMA, and New England
      Journal of Medicine. The main outcome measure was the reporting of participation
      and of results by race/ethnicity of trial participants. Of 253 eligible trials,
      40% (n=102) were non race-focused yet did not report race, while 2% (n=4) were
      non gender-focused and did not report gender. Forty-six percent of trials that
      reported the race/ethnicity of the sample reported only one or two racial/ethnic
      categories, and in 43% of these trials the total number of individuals reported
      in each race/ethnicity category did not equal the total reported sample size.
      Analysis of results by race/ethnicity was reported in only two trials, and by
      gender in only three trials. In diseases with known racial and ethnic
      disparities, many clinical trials do not report the race/ethnicity of the study
      participants, and almost none report analyses by race/ethnicity. Although federal
      initiatives mandate inclusion of minority groups in research, that inclusion has
      not translated to reporting of results that might guide therapeutic decisions.

PMID- 12812815
TI  - Physical activity and nutrition programs for couples: a randomized controlled
      trial.
AB  - Diet and physical activity habits may deteriorate after cohabitation, leading to
      weight gain and increased risk of lifestyle diseases. We carried out a 4-month,
      randomized controlled trial of a diet and physical activity program for couples
      with a 1-year follow-up, comparing two methods of delivery. The program used six
      modules, which, after an initial group session, were mailed to the low-level
      intervention group. In the high-level intervention group, half of the modules
      were mailed, and the others were delivered at interactive group sessions. A
      control group received no intervention. Postintervention and at follow-up,
      physical fitness improved in the high-level group, saturated fat intake decreased
      in both intervention groups, and low-density lipoprotein cholesterol fell in the
      high-level group. Fewer participants in the high-level group became overweight or
      obese. Health promotion for couples can improve health behaviors and potentially
      lower the risk of lifestyle diseases in participants and their future families.

PMID- 12812816
TI  - A simple method to estimate sample sizes for safety equivalence studies using
      inverse sampling.
AB  - Safety equivalence studies may be required to demonstrate that a new procedure or
      process is at least as safe as a previous one. They usually involve low or very
      low outcome rates that are often not precisely determined, making patient-based
      sample sizing uncertain. Using a reverse sampling approach, a method is derived
      from standard equations to estimate the number of events that need to be observed
      to demonstrate equivalence using the confidence interval approach. For instance,
      for a one-sided (nonsuperiority) hypothesis, 5% alpha risk, and 80% power, almost
      100 events need to be observed in each study arm to demonstrate equivalence
      within 30%, or 250 events for 20% equivalence. The number of patients to be
      included can be derived directly from expected event rates.

PMID- 12812817
TI  - Reliability of the Wisconsin Sleep Questionnaire: a French contribution to
      international validation.
AB  - We evaluated the reliability of a French version of the Wisconsin Sleep
      Questionnaire designed to investigate snoring, obstructive apnoeas, and sleeping
      problems. The assessment of reliability included the study of internal
      consistency and the 3 months repeatability of the questionnaire. The
      questionnaire was first completed at a Center of Preventive Medicine by a random
      sample of 122 subjects from the community. Three months later the same form was
      mailed and 82 questionnaires were returned (67.2%). No significant differences
      existed between responders and nonresponders for anthropometric data or life
      habits. The internal consistency in each domain was good or satisfactory
      (Cronbach's alpha=0.67 to 0.81). The concordance between the answers at a 3-month
      interval was excellent for questions on ever snoring, frequency of snoring,
      gasping/choking during sleep, and breathing stops during sleep (Cohen
      kappa>0.60). The questions on snoring loudness, a history of sleep apnoea, and
      excessive daytime sleepiness were fairly reproducible (kappa 0.28 to 0.60). We
      found no difference in reproducibility by gender or age. In conclusion, this
      reliability assessment in a sample of middle-aged subjects from the community in
      northeastern France showed satisfactory internal consistency and 3-months
      reproducibility of the main questions of a French translation of the Wisconsin
      Sleep Questionnaire.

PMID- 12812818
TI  - Internal and external validation of predictive models: a simulation study of bias
      and precision in small samples.
AB  - We performed a simulation study to investigate the accuracy of bootstrap
      estimates of optimism (internal validation) and the precision of performance
      estimates in independent validation samples (external validation). We combined
      two data sets containing children presenting with fever without source
      (n=376+179=555; 120 bacterial infections). Random samples were drawn from this
      combined data set for the development (n=376) and validation (n=179) of logistic
      regression models. The models included statistically significant predictors for
      infection selected from a set of 57 candidate predictors. Model development,
      including the selection of predictors, and validation were repeated in a
      bootstrapping procedure. The resulting expected optimism estimate in the receiver
      operating characteristic (ROC) area was compared with the observed optimism
      according to independent validation samples. The average apparent ROC area was
      0.74, which was expected (based on bootstrapping) to decrease by 0.07 to 0.67,
      whereas the observed decrease in the validation samples was 0.09 to 0.65.
      Omitting the selection of predictors from the bootstrap procedure led to a severe
      underestimation of the optimism (decrease 0.006). The standard error of the
      observed ROC area in the independent validation samples was large (0.05). We
      recommend bootstrapping for internal validation because it gives reasonably valid
      estimates of the expected optimism in predictive performance provided that any
      selection of predictors is taken into account. For external validation,
      substantial sample sizes should be used for sufficient power to detect clinically
      important changes in performance as compared with the internally validated
      estimate.

PMID- 12812819
TI  - Predicting kidney graft failure using time-dependent renal function covariates.
AB  - Chronic rejection and recurrent disease are the major causes of late graft
      failure in renal transplantation. To assess outcome, most researchers use Cox
      proportional hazard analysis with time-fixed covariates. We developed a model
      adding time-dependent renal function covariates to improve the prediction of late
      graft failure. We studied 692 kidney transplants at the Leiden University Medical
      Center that had functioned for at least 6 months. Graft failure from chronic
      rejection or recurrent disease occurred in 106 patients. The reciprocal of last
      recorded serum creatinine (RC), the ratio of RC and RC at 6 months (RC6), and the
      time elapsed since last observation (TEL) were used as time-dependent covariates.
      Cadaveric donor transplantation, a lower RC, and a lower ratio of RC/RC6 were
      independently associated with graft failure. The impact of the last recorded RC
      was dependent on its value, TEL, and the time since transplantation. Validation
      of the model confirmed much higher failure predictions in those with subsequent
      graft failure compared with nonfailures. This study illustrates that the
      prediction of late graft failure could be improved significantly by using time
      dependent renal function covariates.

PMID- 12812820
TI  - The utility of the international child and adolescent overweight guidelines for
      predicting coronary heart disease risk factors.
AB  - The purpose of this study was to assess the association between the international
      overweight cutoffs for children and youth and coronary heart disease risk
      factors. The sample included 410 boys and 337 girls 9-18 years of age from the
      Quebec Family Study. Participants were classified as normal weight or overweight
      using the international BMI cutoffs, and into normal and elevated risk groups
      based on the 90th percentile of sex-specific age-adjusted risk factors [blood
      pressure, fasting total cholesterol (CHOL), LDL-C, HDL-C, CHOL/HDL-C,
      triglycerides, glucose, and physical work capacity]. Overweight participants had
      between 1.6 and 9.1 times the risk of elevated risk factors compared to normal
      weight participants. Further, boys and girls with four or more risk factors were
      19 and 43 times more likely to be overweight, respectively, compared to
      participants with no risk factors. The results add evidence that the
      international cutoffs are related to health risks in youth, supporting the
      adoption of the guidelines.

PMID- 12812822
TI  - The protective effect of social engagement on 1-year mortality in a long-stay
      nursing home population.
AB  - We examined the effect of social engagement (SE) on mortality in 30,070 long-stay
      nursing home residents who were > or =65 years of age and did not have a serious
      communication problem. Information on SE and resident characteristics were
      obtained from the Minimum Data Set, and death information was obtained from the
      National Death Index. Life table analyses show that greater levels of SE are
      associated with longer survival (P=.0001). Adjusted proportional hazards
      regression results show that for each increase in the SE scale, residents are
      0.94 (range 0.92-0.95) times as likely to die during the follow-up period,
      independent of known factors associated with mortality. Future studies are needed
      to understand psychological and other factors related to residents' capacity and
      motivation for social engagement that could increase quality and quantity of life
      in nursing home residents.

PMID- 12812821
TI  - Cross-sectional and longitudinal associations of low-back pain and related
      disability with psychological distress among patients enrolled in the UCLA Low
      Back Pain Study.
AB  - The objectives of the study are to test the hypotheses that psychological
      distress affects subsequent low-back pain, and pain affects subsequent distress.
      Six hundred eighty-one participants in a randomized clinical trial of low-back
      pain treatments were followed for 18 months with assessments for pain,
      disability, and psychological distress at 6 weeks and 6, 12, and 18 months.
      Multivariable logistic regression modeling with generalized estimating equations
      was used to estimate effects. Current pain and disability increased the odds of
      subsequent psychological distress [pain: adjusted odds ratio (OR)=1.36, 95%
      confidence interval (CI)=1.07, 1.72; disability: adjusted OR=1.23, 95% CI=0.98,
      1.55], and current distress increased the odds of subsequent pain and disability
      (pain: adjusted OR=1.51, 95% CI=1.24, 1.86; disability: adjusted OR=1.49; 95%
      CI=1.20, 1.85). Cross-sectional associations were much stronger than the
      longitudinal associations, suggesting bias in the former due to selection factors
      and/or temporal ambiguity. The longitudinal findings suggest that pain/disability
      and psychological distress may be causes and consequences of each other, although
      the associations are small.

PMID- 12812823
TI  - Age-related changes in risk factor effects on the incidence of thromboembolic and
      hemorrhagic stroke.
AB  - We examined the changes in risk factor effects on the incidence of thromboembolic
      and hemorrhagic stroke as they may occur with age. Findings were based on
      repeated risk factor measurements at four examinations over a 26-year period in
      7589 men in the Honolulu Heart Program. After each examination, 6 years of follow
      up were available to assess risk factor effects on the incidence of stroke over a
      broad range of ages (45-93 years). As compared with normotensive men, the risk of
      thromboembolic stroke in the presence of hypertension declined from a 7-fold
      excess in men aged 45 to 54 years to a 1.4-fold excess in men aged > or =75
      (P<.001). Adverse effects of diabetes and atrial fibrillation seemed to be
      equally important across all ages, whereas a protective effect of physical
      activity increased with age. Except for men with atrial fibrillation, the
      incidence of thromboembolic stroke increased significantly with age regardless of
      risk factor status, including men with normal blood pressure (P<.001). Although
      hemorrhagic events were less common, positive relations with cigarette smoking
      seemed to strengthen with age, whereas those with hypertension tended to decline.
      Our findings suggest that strategies for the prevention of stroke may need to
      account for changes in risk factor effects as they occur with age. Control of
      diabetes and the encouragement of active lifestyles in the elderly seem to be
      especially important.

PMID- 12812824
TI  - Geographic variation within the United States in the incidence of hepatocellular
      carcinoma.
AB  - Geographic variation in hepatocellular carcinoma (HCC) has not been previously
      studied in the United States. Using data collected by the Surveillance,
      Epidemiology, and End Results registries (SEER) and the 1990 Behavioral Risk
      Factor Surveillance System (BRFSS), we analyzed incidence and risk factors for
      HCC in nine geographic regions in the United States. We identified all
      individuals with HCC during 1975-1998 in five states (Connecticut, Iowa, Utah,
      New Mexico, and Hawaii) and four metropolitan areas (Detroit-Metropolitan, San
      Francisco-Oakland, Seattle-Puget Sound, and Atlanta-Metropolitan). Age-adjusted
      incidence rates were calculated for each geographic region. The association
      between HCC incidence and geographic regions were examined in Poisson
      multivariate regression model controlling for age, gender, race, and year of
      diagnosis. Hierarchical linear modeling was also used to examine these
      associations while adjusting for potential clustering of persons with similar
      characteristics within geographic regions, and to assess the effect of the
      prevalence of smoking, alcohol use, obesity, and diabetes in the underlying
      population in these geographical regions. A total of 11,547 persons with HCC were
      examined. Hawaii had the highest age-adjusted incidence rate (4.6), followed by
      San Francisco-Oakland (3.2), New Mexico (2.0), Detroit-Metropolitan (1.9),
      Seattle-Puget Sound (1.8), Atlanta-Metropolitan (1.7), Connecticut (1.6), Iowa
      (1.1), and Utah (1.0); all rates per 100,000. Whites had an age-adjusted
      incidence rate of 1.5, Blacks 3.2, and other races "Asian, American Indian,
      Pacific Islander" 7.0. However, Blacks and "other races" in Seattle-Puget Sound
      had higher age-adjusted incidence rates (4.4 and 8.2, respectively) than Blacks
      and other races in any other registry, while Whites in Hawaii had a higher rate
      (2.5) than Whites in any other registry. In general, men had a two to three times
      higher age-adjusted incidence rate than women. However, Hawaiian men had
      significantly higher age-adjusted rates (7.0) than men in other regions, while
      Utah had the lowest rates of HCC in men (1.5). Adjusting for variations in
      ethnicity, gender, age, and time of diagnosis, the Poisson regression analysis
      showed persistent geographic differences in HCC as well as a change in the order
      with New Mexico having the highest HCC incidence followed San Francisco-Oakland.
      Hierarchical linear modeling confirmed geographic variations in HCC but failed to
      show a significant effect for the prevalence of smoking, alcohol use, obesity,
      and diabetes in the underlying population. Significant geographic variation in
      HCC incidence exist in the United States. These variations are only partly
      explained by differences in age, gender, race, and year of diagnosis.

PMID- 12812825
TI  - Mortality trend from sporadic Creutzfeldt-Jakob disease (CJD) in Italy, 1993
      2000.
AB  - The objective was to identify any possible cases of variant Creutzfeldt-Jakob
      disease (CJD) in Italy, and to estimate the trends in mortality from sporadic CJD
      for 1993-2000. CJD cases were ascertained through direct notification to the
      Registry; 382 definite or probable sporadic CJD patients, but no cases of variant
      CJD were identified. The average yearly mortality rate was 1.04 cases per million
      inhabitants, with an increase in deaths in the 60-69 and > or =70 year age
      groups. Survival was shorter in male respect to female and in patients with an
      age at onset > or =65 years. CJD cases were uneven distributed among different
      regions in the period 1993-1995, but not herein after. The rise in mortality from
      sporadic CJD in Italy likely reflects increased awareness and better diagnosis
      during the years. However, continuous notification and postmortem examination of
      all suspected cases are recommended for optimal surveillance.

PMID- 12812826
TI  - Periodic abstinence enhances nociception without significantly altering the
      antinociceptive efficacy of spinal morphine in the rat.
AB  - Naloxone administration in the opioid dependent rat is associated with spinal
      glutamate release and NMDA receptor activation which reportedly is also
      responsible for opioid tolerance. We hypothesized that episodic withdrawal during
      chronic infusion of spinal morphine might paradoxically enhance tolerance. Rats
      (24/group) infused with intrathecal morphine (M) for 4 days (20 nmol/microl per
      h) were given a daily subcutaneous (s.c.) injection of naloxone 0.6 mg/kg per 0.2
      ml (MN) or saline 0.2 ml (MS). A third saline infused group was given daily s.c.
      saline 0.2 ml (SS). Latencies (rear paw hot box) were tested immediately prior to
      each daily injection. After termination of each infusion, the dose effect of
      spinal morphine (0.1, 1, 10, and 100 nmol) was examined. The MN group showed a
      significantly greater decline in daily latencies compared with the MS group, but
      also had greater withdrawal hyperalgesia upon termination of the infusion. Dose
      response to spinal morphine was not significantly different in either MS or MN
      groups. Periodic abstinence thus enhanced nociception without significantly
      altering the antinociceptive effect of spinal morphine in this group.

PMID- 12812827
TI  - Adrenocorticotropic hormone (MC-2) receptor mRNA is expressed in rat sympathetic
      ganglia and up-regulated by stress.
AB  - Stress triggered cardiovascular disorders are associated with elevated activity
      of the sympathetic nervous system, the major source of elevated plasma
      norepinephrine levels. Our previous studies revealed that administration of
      adrenocorticotropic hormone (ACTH) increases the gene expression of
      norepinephrine biosynthetic enzymes and several neuropeptides in rat sympathetic
      ganglia as much as stress. Here, we examine whether an ACTH-responsive receptor
      is expressed in rat superior cervical (SCG) and stellate ganglia (StG). Using
      reverse transcriptase-polymerase chain reaction (RT-PCR) we found expression of
      MC-2 receptor mRNA in these ganglia. Identical DNA fragments were amplified with
      mRNA from SCG, StG or from adrenal cortex. Sequencing revealed extensive homology
      to published sequences of mouse and human MC-2 receptor. Real time PCR was used
      to quantitate MC-2 receptor mRNA levels in the SCG under basal conditions and
      following immobilization stress. Immobilization stress triggered a large increase
      in MC-2 receptor mRNA in SCG. The results provide the first evidence that rat
      sympathetic ganglia express MC-2 receptor gene and are a target tissue for the
      peripheral actions of ACTH in response to stress.

PMID- 12812828
TI  - Contribution of nitric oxide to the depression of neuronal activity induced by
      temperature increase in the rat hippocampal CA1 area.
AB  - Using optical recording techniques, we examined whether nitric oxide (NO) is
      implicated in the impairment of the activity of hippocampal CA1 neurons induced
      by mild heat stress. A temperature increase from 32 to 38 degrees C reversibly
      depressed the neuronal activity in hippocampal slices. L-Arginine (1 mM), an NO
      donor, enhanced the heat-induced depression of the activity of hippocampal CA1
      neurons. N(omega)-Nitro-L-arginine methyl ester, an inhibitor of nitric oxide
      synthase, attenuated the inhibition of the neuronal activity induced by a
      temperature increase. Methylcobalamin (10 microM), a vitamin B(12) analogue that
      reduces NO production, reduced the heat-induced depression of the neuronal
      activity. These results suggest that NO contributes, at least in part, to the
      heat-induced depression of the neuronal activity in the hippocampal CA1 region.

PMID- 12812829
TI  - Evidence of dopamine D1 receptor mRNA and binding sites in cultured human
      amniotic epithelial cells.
AB  - In this study, we employed RT-PCR and radioligand binding studies to evaluate the
      gene expression and binding characteristics, respectively, of dopamine D(1)
      receptors in human amniotic epithelial cells (HAEC). The results showed that HAEC
      natively expressed D(1) receptor mRNA, as measured by RT-PCR, which was identical
      to that of human brain. Saturation binding studies using [(3)H]SCH 23390
      demonstrated the presence of a high affinity D(1) site in HAEC with K(D) and
      B(max) values of 2.01+/-0.25 nM and 32.5+/-3.7 fmol/mg protein, respectively.
      Competition studies showed that selective D(1) antagonists were potent displacers
      of [(3)H]SCH 23390 binding with a potency order consistent with D(1) receptor
      characteristics. The current results present compelling evidence that HAEC
      natively express D(1) receptor mRNA and binding sites. The results also establish
      a primate cell model that can possibly be used for studying D(1) receptor signal
      transduction and molecular mechanisms and exploring newly developed drugs acting
      at these receptors.

PMID- 12812830
TI  - The human supplementary motor area-proper does not receive direct somatosensory
      inputs from the periphery: data from stereotactic depth somatosensory evoked
      potential recordings.
AB  - Somatosensory evoked potentials to median nerve (MN) stimulation were recorded by
      stereotactically implanted electrodes in the frontal lobe of two epileptic
      patients in order to evaluate whether short-latency cortical responses could be
      generated in the supplementary motor area (SMA)-proper. In both patients two
      potentials, called P20 and N30 responses, showed a decreasing amplitude from the
      most superficial to the deepest contacts and were recorded in the white as well
      in the grey matter of the frontal lobe. Furthermore, no phase reversal of both
      P20 and N30 potentials was identifiable along electrode trajectories. Our results
      suggest that short-latency somatosensory evoked responses recorded in the SMA
      proper contralateral to MN stimulation are volume conducted from remote cortical
      generators.

PMID- 12812831
TI  - Expression of vascular endothelial growth factor and its receptors in rat neural
      stem cells.
AB  - Neural stem cells serve neurogenesis in several areas of the adult mammalian
      brain. The present study investigates an additional feature, i.e. the expression
      of vascular endothelial growth factor (VEGF) and its receptors in cultured
      neurospheres from hippocampus, subventricular zone, and olfactory bulb in adult
      rats. RT-PCR showed that all three lines expressed VEGF mRNA, but different sets
      of VEGF receptor mRNAs. Stimulation by either 50 ng/ml VEGF-A165 or by 24 h of
      anoxia resulted in an altered pattern of receptor expression for VEGF-R2 (Flk-1),
      VEGF-R3 (Flt-4), neuropilin-1, and neuropilin-2, whereas VEGF-R1 (Flt-1) remained
      unexpressed. The basal expression of VEGF and of several of its receptor mRNAs
      indicates a hitherto unknown angiogenic potential of neural stem cells.

PMID- 12812832
TI  - Sex differences in brain activation pattern during a visuospatial cognitive task:
      a functional magnetic resonance imaging study in healthy volunteers.
AB  - Sex differences in mental rotation tasks, favoring men, have been noted in
      behavioral studies and functional imaging studies. In the present study ten
      female and ten male volunteers underwent functional magnetic resonance imaging in
      a conventional block design. Regions of activation were detected after
      performance of a mental rotation task inside the scanner. In contrast to previous
      studies, confounding factors such as performance differences between genders or
      high error rates were excluded. Men showed significantly stronger parietal
      activation, while women showed significantly greater right frontal activation.
      Our results point to gender specific differences in the neuropsychological
      processes involved in mental rotation tasks.

PMID- 12812833
TI  - Differentiating effects of anisodamine on cognitive amelioration and peripheral
      muscarinic side effects induced by pilocarpine in mice.
AB  - Based on the cholinergic hypothesis of Alzheimer's disease (AD), many
      cholinomimetics have been tested for the treatment of AD. Although some of them
      have beneficial effects, peripheral muscarinic side effects limit their utility.
      Our present experiments showed that muscarinic agonist pilocarpine (pilo) could
      significantly improve memory deficits induced by scopolamine in step-through
      task, but be accompanied by pronounced peripheral cholinergic side effects such
      as hypersalivation, bradycardia, diarrhea and so on. Anisodamine (aniso) is a
      peripheral muscarinic blocker isolated from a Chinese herb Anisodus tanguticus
      and is widely used in China. When combined with aniso, pilo preserved its central
      efficacy with very minor peripheral side effects. Cholinomimetics combined with
      peripheral muscarinic blockers may provide alternative therapeutic strategies for
      AD.

PMID- 12812834
TI  - The role of the human supplementary motor area in reactive motor operation.
AB  - The role of the supplementary motor area (SMA) in reactive motor operation was
      investigated with functional magnetic resonance imaging in 13 normal subjects. A
      visual cue was presented at a regular (1 Hz) or irregular (mean, 1 Hz) rate, and
      the subject pressed a button with the right index finger in a predictive or
      reactive manner. Brain regions associated with reactive movement were detected by
      comparing reactive with predictive movement tasks, and those with irregular
      movement by comparing irregular and regular cueing tasks. During regular cueing,
      the SMA showed greater activation for reactive than predictive movement. However,
      the SMA was equally activated between regular and irregular cueing once the
      subject reacted to the cue. The SMA is likely involved in reactive adjustment of
      movement to the external cue.

PMID- 12812835
TI  - Tracking of multiple sound sources defined by interaural time differences: brain
      potential evidence in humans.
AB  - Among other cues, interaural time differences (ITD) can be used to compute the
      location of a sound. To investigate whether ITD can be used for the preattentive
      detection of sounds coming from a different location than standard sounds (P=0.7,
      no ITD), left and right 'far' (900 micros ITD, 80 degrees excentricity) and 'near
      ' (300 micros ITD, 30 degrees ) deviant stimuli (each deviant P=0.075) were
      presented via headphones. While 15 young healthy subjects passively listened to
      these sequences, the mismatch negativity (MMN) of the event-related potential was
      obtained for the deviant sounds. MMN was reliable for all four deviants but
      larger for the far-lateralized sounds. Moreover, MMN was larger contralateral to
      the location of the deviant. This indicates a role of preattentive mechanisms in
      the spatial analysis of auditory scenes.

PMID- 12812836
TI  - Macrophage colony stimulating factor promotes phagocytosis by murine microglia.
AB  - Macrophage colony stimulating factor (M-CSF) and its receptor are upregulated in
      the brain in Alzheimer's disease. M-CSF induces activation and proliferation of
      microglial cells and expression of proinflammatory cytokines. Amyloid beta
      (Abeta) immunization experiments suggest that microglia have the capacity to
      aggressively clear Abeta from the brain under certain circumstances. We examined
      the role of M-CSF in phagocytosis of fluorescent microspheres and Abeta by
      cultured microglia. M-CSF treatment increased microglial cell phagocytosis of
      both microspheres and of Abeta. Antibody neutralization of M-CSF inhibited Abeta
      uptake induced by overexpression of the M-CSF receptor on microglia. These
      results suggest that M-CSF could be important in promoting microglial clearance
      of abnormal protein aggregates such as Abeta.

PMID- 12812837
TI  - Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate
      the risk of neural tube defects in humans.
AB  - The pathogenic mechanism of neural tube defects may involve genetic polymorphisms
      and nutritional factors related to homocysteine metabolism. We evaluated the
      association of polymorphisms of three genes affecting vitamin B12-dependent
      remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and
      MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase
      (MTHFR), with the risk of having neural tube defect in 40 children with spina
      bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG
      /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds
      ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In
      contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion,
      genetic determinants affecting the cellular availability or MTRR-dependent
      reduction of B12 may increase the risk of spina bifida.

PMID- 12812838
TI  - Phenotypic modulation of smooth muscle cells and vascular remodeling in
      intraparenchymal small cerebral arteries after canine experimental subarachnoid
      hemorrhage.
AB  - Cerebral microcirculatory changes are an important factor regulating cerebral
      blood flow. The aim of this study was to investigate the possibility of
      phenotypic modulation of smooth muscle cell (SMC) and vascular remodeling of
      intraparenchymal small cerebral arteries after subarachnoid hemorrhage (SAH).
      Seven to 14 days after canine experimental SAH, in intraparenchymal perforating
      arteries, the amount of beta-actin mRNA evaluated by Northern blot analysis
      increased, the structural change of the 3' untranslated region of beta-actin mRNA
      detected by polymerase chain reaction analysis was enhanced, and
      immunohistochemistry showed marked induction of the embryonal isoform of myosine
      heavy chain accompanied by decreased expression of smooth muscle myosin heavy
      chain (SM2). Histological morphometric analysis showed an increase in the area of
      the arterial wall without changes in the number of nuclei of SMC. This is the
      first report suggesting that vascular remodeling accompanied by phenotypic
      modulation occurs in intraparenchymal small arteries. These changes may affect
      cerebral blood flow after SAH by inducing increased cerebrovascular resistance.

PMID- 12812839
TI  - Differential patterns of c-fos mRNA expression in the amygdaloid nuclei induced
      by chemical somatic and visceral noxious stimuli in rats.
AB  - Pain includes a negative affective component, although the neural system is
      unclear. The amygdala including the lateral (La), basolateral (BL) and central
      (Ce) nuclei is thought to play a key role in emotional responses. In this study,
      we analyzed the c-fos mRNA expression, as a marker of neuronal activity, induced
      by two types of pain, chemical somatic and visceral noxious stimuli, in each
      amygdaloid nucleus in unanesthetized rats. We found that intraplantar injection
      of formalin as a chemical somatic noxious stimulus increased c-fos mRNA
      expression in the La and BL, but not Ce. On the other hand, intraperitoneal
      injection of acetic acid as a chemical visceral noxious stimulus induced it
      highly in the Ce, moderately in La and hardly in BL. These results suggest that
      distinct amygdaloid nuclei are activated by chemical somatic and visceral noxious
      stimuli, which might differentially contribute to emotional responses by them.

PMID- 12812840
TI  - Inhibiting caspase-9 after injury reduces hypoxic ischemic neuronal injury in the
      cortex in the newborn rat.
AB  - A broad spectrum caspase inhibitor reduces hypoxic ischemic brain injury. We
      hypothesized that a specific caspase-9 inhibitor would provide similar
      protection. Seven-day-old rat pups had the right carotid artery ligated, then
      were subjected to 2.5 h of 8% oxygen. Caspase-9 activity in the right cortex was
      measured enzymatically. Caspase-9 activity was increased at 6, 12, and 24 h after
      injury. LEHD-CHO is a specific cell permeable caspase-9 inhibitor. LEHD-CHO given
      intracerebroventricularly (i.c.v.) into the brain after the hypoxic period
      eliminated the increase in caspase-9 activity. The greatest effect was at a dose
      of 50 microg/pup (1.6 micromol/kg). Fifty-two pups were randomly assigned to
      receive 50 microg/pup of i.c.v. LEHD-CHO or vehicle immediately after the hypoxic
      period. The loss of cortical neurons in the right hemisphere 22 days after injury
      was 52.0+/-8% in the vehicle treated animals, and 25+/-9% in the LEHD-CHO treated
      animals (P<0.05). Inhibiting caspase-9 activity reduces loss of neurons after
      brain injury.

PMID- 12812841
TI  - Circadian rhythms in humans' delta sleep electroencephalogram.
AB  - Eight healthy young male volunteers entered a 20-40 min ultrashort sleep-wake
      schedule for 78 h in the time-isolation facility. Rectal temperature was
      continuously recorded. Sleep electroencephalograms (EEGs) obtained during 20 min
      nap trials were stored in the computer and later analyzed by fast Fourier
      transform. A two-way repeated-measures ANOVA (with day and time-of-day as the
      repeated measures) revealed significant circadian rhythms in the powers of sigma
      and delta sleep EEGs, and in rectal temperature. These results obtained under
      conditions in which behavioral confounding factors of retiring and rising were
      experimentally minimized suggest that the circadian pacemaker contributes to
      determining the hours of day when one can sleep deeply.

PMID- 12812842
TI  - Nitric oxide mediates membrane depolarization-promoted survival of rat neuronal
      PC12 cells.
AB  - Membrane depolarization promotes neuronal survival through increases in
      intracellular calcium. Nitric oxide (NO) is a signaling molecule involved in many
      neuronal activity-dependent events. Since neuronal NO is generated by NO synthase
      (NOS) in a calcium-dependent manner and was shown to promote cell survival, we
      tested whether NO is involved in depolarization-promoted survival in neuronally
      differentiated PC12 cells. NOS inhibitor attenuated depolarization-promoted
      survival and NO donors promoted survival. This effect was partially cGMP
      dependent as a guanylyl cyclase inhibitor decreased NO-promoted survival. Ras
      inhibitor, Erk blocker or phosphatidylinositol 3-kinase inhibitor decreased
      depolarization- or NO donor-promoted survival. Depolarization-induced Ras
      activation was blocked by NOS inhibitor. Inducible expression of dominant
      negative Ras or S-nitrosylation-defective Ras attenuated depolarization- or NO
      donor-promoted survival. Thus, NO might be a mediator via Ras and cGMP pathways
      in depolarization-promoted survival in neuronal PC12 cells.

PMID- 12812843
TI  - Age-related changes in the release and uptake activity of presynaptic axon
      terminals of rat locus coeruleus neurons.
AB  - Age-related changes in the release and uptake activity of presynaptic axon
      terminals of rat locus coeruleus (LC) noradrenergic neurons were studied in the
      frontal cortex using an extracellular single unit recording technique in vivo.
      Clonidine, a selective alpha(2) adrenergic agonist, and nisoxetine, a selective
      noradrenaline uptake inhibitor, were infused locally into the frontal cortex to
      examine the effects of these drugs on release and uptake activities of the axon
      terminals of LC neurons. Although the infusion of clonidine produced a marked
      suppression of release, the effect did not change with age. Infusion of
      nisoxetine caused an inhibition of uptake, but the effect was attenuated in aged
      rats. These results suggest that the release activity mediated by the presynaptic
      autoreceptor did not change with age, but the uptake activity mediated by the NA
      transporter declined with age in the axon terminals of LC neurons.

PMID- 12812844
TI  - Omission of radiotherapy after breast-conserving surgery: survival impact and
      time trends.
AB  - PURPOSE: To evaluate the survival impact of omission of radiotherapy after breast
      conserving surgery and the changes with time. MATERIAL AND METHODS: Women aged 40
      69 with non-metastasized T1-T2 breast cancer, who underwent breast-conserving
      surgery with axillary node dissection, with or without post-surgery radiotherapy,
      selected from the SEER (Surveillance, Epidemiology, and End Results) database.
      The analysis uses proportional hazards models. RESULTS: Omission of radiotherapy
      as compared to delivery of radiotherapy was associated with an overall increased
      mortality hazard ratio of 1.346 (95% confidence interval: 1.204-1.504). Test of
      constancy showed significant changes with time. The time profile suggested an
      exponential-like increase from a baseline mortality hazard ratio of 1.17, or 17%
      excess of relative mortality risk, to a projected hazard ratio of 2.26, or more
      than doubling of relative mortality risk, for omission of radiotherapy.
      CONCLUSION: Omission of radiotherapy in breast-conserving surgery is found to be
      independently associated with an increase in mortality. The data do not give
      support to omitting radiation or give rationale to clinical trials that would
      omit radiation.

PMID- 12812845
TI  - A comparison in cosmetic outcome between per-operative interstitial breast
      implants and delayed interstitial breast implants after external beam
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the
      breast conserving therapy of breast cancer can be performed in two ways; implants
      during the tumor excision (per-operative implants) or after the external beam
      therapy (delayed interstitial implants). Differences in cosmetic outcome were
      investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per
      operative implant were compared to 123 patients having a delayed interstitial
      implant in a matched case-control study. Cosmesis was scored on a four-point
      scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63
      months, three observers found no difference in cosmetic outcome between the two
      groups after adjustment for variables found to be related with cosmesis
      (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not
      found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34
      cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing
      per-operative implants has not led to smaller implants. The method of performing
      brachytherapy does not result in marked differences in cosmetic outcome.

PMID- 12812846
TI  - Evaluation of the dosimetric consequences of adding a single asymmetric or MLC
      shaped field to a tangential breast radiotherapy technique.
AB  - Fifteen consecutive patients had standard treatment plans generated using our
      departmental protocol and two further plans produced using either an asymmetric,
      or MLC shaped additional field, from each tangential direction. The mean
      percentage of the PTV receiving over 107% of the isocentre dose was 19.8% for the
      standard planned patients (95% confidence interval 12.3-27.4%). This was reduced
      to 6.0% for the asymmetric field technique (95% confidence interval 4.1-8.0%) and
      5.3% for the MLC technique (95% confidence interval 2.8-7.7%). These high dose
      volume reductions were therefore significant at the 95% confidence level. It was
      also concluded that both alternative planning techniques offer the greatest
      potential when the standard plan indicated that more than 20% of the PTV would
      receive greater than 107% of the prescribed dose. Under these circumstances the
      segmented field techniques led to a reduction of at least 15 percentage points in
      this figure. It is this group of patients who stand to benefit most from
      application of these simple additional field techniques.

PMID- 12812847
TI  - Pattern of failures in gastric cancer patients with lymph node involvement
      treated by surgery, intraoperative and external beam radiotherapy.
AB  - AIMS: High local failure rates in gastric cancer have been reported, up to 67%.
      To achieve a better local control, we evaluated intraoperative radiotherapy
      (IORT) and external beam radiotherapy (EBRT) in association with surgery for
      gastric cancer patients with lymph node involvement. We report here the analysis
      of the patterns of failure for patients involved in this IORT protocol. MATERIAL
      AND METHODS: Forty-two positive lymph node (N+) gastric cancer patients were
      operated on (31 total, three subtotal and eight extended gastrectomies) with IORT
      procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years).
      IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in
      36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic
      chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients.
      RESULTS: One patient died postoperatively. Actuarial pN+ 10 year survival rate
      was 44.8%. The 5 year actuarial local control and disease-free survival rates
      were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5
      patients have a local coeliac recurrence (12%) and 12 have distant metastases
      with no evidence of coeliac recurrence. CONCLUSION: This retrospective analysis
      suggests a potential effect of IORT and/or EBRT in promoting local control and
      long-term survival in gastric cancer patients with lymph node involvement.

PMID- 12812848
TI  - Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair
      survival analysis with MRC controls.
AB  - PURPOSE: To assess the survival benefit of palliative hypofractionated
      radiotherapy in patients with poor prognosis high grade glioma by a matched
      comparison to conventionally treated controls. METHOD: Ninety-two elderly and/or
      disabled patients with high grade glioma with poor prognostic features received
      palliative partial brain radiotherapy to a dose of 30Gy in six fractions over 2
      weeks. Patients were matched for WHO histological grade, performance status and
      age from a cohort of patients treated with conventionally fractionated
      radiotherapy to a dose of 60Gy in 30 fractions in an Medical Research Council
      (MRC) BR05 trial. RESULTS: Patients treated with hypofractionated radiotherapy
      had a median survival of 5 months with a 1-year survival rate of 12% from
      diagnosis. The median survival of case-matched controls was estimated to be 2.5
      4.5 months longer. Following hypofractionated radiotherapy, Barthel score was
      improved or remained stable in 68% of patients. CONCLUSION: Hypofractionated
      partial brain radiotherapy is a well-tolerated regimen with palliative benefit.
      Comparison with matched controls suggests lesser survival benefit than would be
      obtained with radical radiotherapy. However, this is compensated by lower
      intensity and duration of irradiation induced side effects. It is postulated that
      there may not be a significant difference in good quality survival or 'quality
      adjusted survival' between the two regimens and this requires testing in
      prospective trials.

PMID- 12812849
TI  - Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in
      patients with high-grade gliomas.
AB  - PURPOSE: To determine the value and the toxicity of an additional fractionated
      stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in
      patients with malignant gliomas. MATERIALS AND METHODS: Seventeen patients (11
      male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) < or =4 cm in
      maximum diameter, with a good performance status (WHO > or =2), were treated with
      a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions
      following partial brain irradiation to a dose of 60 Gy in 30 fractions. This
      patient group was compared with historical data in a matched-pair analysis.
      RESULTS: All patients were treated by conventional radiotherapy and a SRT boost
      (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included
      fatigue (two), impairment of short-term memory (one) and worsening of pre
      existing symptoms (one). No patient developed steroid dependence after SRT. One
      patient was re-operated for radiation necrosis. At a median follow-up of 25
      months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and
      42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years
      for all patients, respectively. Median survival for the whole patient group is 20
      months. Comparison with a matched historical group showed a significantly better
      survival for the group treated with a stereotactic boost (P<0.0001). CONCLUSION:
      A fractionated stereotactic boost after standard external beam radiotherapy in
      selected patients with high-grade glioma is feasible and well tolerated with low
      toxicity. Compared to historical data survival is significantly better with an
      additional SRT boost. However, its effectiveness has to be proven in a randomized
      trial.

PMID- 12812850
TI  - Stereotactic conformal radiotherapy for posterior fossa tumours: a modelling
      study for potential improvement in therapeutic ratio.
AB  - PURPOSE: To investigate the optimal technique of stereotactic conformal
      radiotherapy (SCRT) for posterior fossa tumours. MATERIAL AND METHODS: SCRT
      planning image data sets of four patients with posterior fossa tumours
      constituted the study material. Based on the operative notes and preoperative
      imaging, a clinical target volume (CTV) was drawn for each patient. An additional
      CTV representative of a typical posterior fossa tumour was also drawn on each
      patient's localisation scans. Therefore a total of eight CTVs differing in their
      size and location were used for further work. A margin of 5 mm was grown in three
      dimensions to result in a final planning target volume (PTV). Beam arrangements
      studied were conformal bilateral parallel pair, a three-field coplanar
      arrangement with two bilateral and a vertex beam, two three-field non-coplanar
      techniques and a six-field non-coplanar technique with conformation achieved by
      micromultileaf collimator (mMLC). Normal structures contoured included normal
      posterior fossa brain (excluding PTV), brain stem, cochleae, optic apparatus,
      pituitary-hypothalamic axis (PHA), supratentorial brain and the temporal lobes.
      Comparative evaluation of plans was done with dose volume histograms (DVH),
      conformity index (CI) and dose heterogeneity (DH). RESULTS: In all plans, the 95%
      isodose line covered at least 99% of the PTV with acceptable dose heterogeneity.
      As compared to the baseline bilateral conformal parallel pair plan, all other
      plans achieved significantly more sparing of the normal posterior fossa brain at
      the 95 and 80% dose prescription levels with superior CI (at 95% isodose). The
      six-field technique resulted in maximum sparing as compared to the bilateral plan
      with a mean additional sparing of 74% (46.2 cm3) and 55% (33.83) at 95 and 80%
      dose prescription level, respectively (P<0.0001). Among the three field plans,
      the technique of bilateral and vertex fields resulted in least doses to cochlea
      and also irradiated the least volume of brain stem and PHA. Comparison of this
      technique to the six-field technique did not show any significant difference in
      sparing of normal structures in the posteriorly placed tumours. In anteriorly
      placed tumours, the six-field technique was the most optimal irrespective of the
      size of the target volumes. CONCLUSIONS: A six-field plan SCRT achieves the most
      significant sparing of the normal tissues for localised irradiation in posterior
      fossa tumours, particularly for anteriorly located tumours. A relatively simpler
      three-field plan with bilateral and a vertex beam is equally good for tumours
      that are placed posteriorly and away from the brain stem.

PMID- 12812851
TI  - LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical
      experience.
AB  - PURPOSE: To study local tumor control and radiogenic side effects after
      fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma.
      PATIENTS AND METHODS: Between June 1997 and March 2001, 90 patients suffering
      from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized
      with a modified stereotactic frame system (BrainLAB). For stabilization of the
      eye position a light source was integrated into the mask system in front of the
      healthy or the diseased eye. A mini-video camera was used for on-line eye
      movement control. Tumors included in the study were either located unfavorably
      with respect to macula and optical disc (<3 mm distance) or presented with a
      thickness >7 mm. Median tumor volume was 305+/-234 mm3 (range 70-1430 mm3), and
      mean tumor height was 5.4+/-2.3 mm (range 2.7-15.9 mm). Total doses of 70 (single
      dose 14 Gy @ 80% isodose) or 60 Gy (single dose 12 Gy @ 80% isodose) were applied
      in five fractions within 10 days. The first fractionation results in total dose
      (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding
      values for the second fractionation schedule are 135 and 180 Gy, respectively.
      RESULTS: After a median follow-up of 20 months (range 1-48 months) local control
      was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and
      37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases.
      Secondary enucleation was performed in seven patients (7.7%). Long term side
      effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and
      secondary neovascular glaucoma (8.8%). CONCLUSION: Fractionated LINAC based
      stereotactic photon beam therapy in conjunction with a dedicated eye movement
      control system is a highly effective method to treat unfavorably located uveal
      melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be
      sufficient to achieve good local tumor control.

PMID- 12812852
TI  - Quality assurance experience with the randomized neuropathic bone pain trial
      (Trans-Tasman Radiation Oncology Group, 96.05).
AB  - BACKGROUND AND PURPOSE: Trans-Tasman Radiation Oncology Group 96.05 is a
      prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in
      five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases.
      This paper summarizes the quality assurance (QA) activities for the first 234
      patients (accrual target 270). MATERIALS AND METHODS: Independent audits to
      assess compliance with eligibility/exclusion criteria and appropriateness of
      treatment of the index site were conducted after each cohort of approximately 45
      consecutive patients. Reported serious adverse events (SAEs) in the form of
      cord/cauda equina compression or pathological fracture developing at the index
      site were investigated and presented in batches to the Independent Data
      Monitoring Committee. Finally, source data verification of the RT prescription
      page and treatment records was undertaken for each of the first 234 patients to
      assess compliance with the protocol. RESULTS: Only one patient was found
      conclusively not to have genuine neuropathic pain, and there were no detected
      'geographical misses' with RT fields. The overall rate of detected infringements
      for other eligibility criteria over five audits (225 patients) was 8% with a
      dramatic improvement after the first audit. There has at no stage been a
      statistically significant difference in SAEs by randomization arm. There was a
      22% rate of RT protocol variations involving ten of the 14 contributing centres,
      although the rate of major dose violations (more than +/-10% from protocol dose)
      was only 6% with no statistically significant difference by randomization arm
      (P=0.44). CONCLUSIONS: QA auditing is an essential but time-consuming component
      of RT trials, including those assessing palliative endpoints. Our experience
      confirms that all aspects should commence soon after study activation.

PMID- 12812853
TI  - Does nutrition influence quality of life in cancer patients undergoing
      radiotherapy?
AB  - PURPOSE: To investigate in cancer patients referred for radiotherapy (RT): (1)
      quality of life (QoL), nutritional status and nutrient intake, at the onset and
      at the end of RT; (2) whether individualised nutritional counselling, despite
      symptoms, was able to enhance nutrient intake over time and whether the latter
      influenced the patient's QoL; and (3) which symptoms may anticipate poorer QoL
      and/or reduced nutritional intake. MATERIAL AND METHODS: One hundred and twenty
      five patients with tumours of the head-neck/gastrointestinal tract (high-risk:
      HR), prostate, breast, lung, brain, gallbladder, uterus (low-risk: LR) were
      evaluated before and at the end of RT. Nutritional status was evaluated by
      Ottery's Subjective Global Assessment, nutritional intake by a 24-h recall food
      questionnaire and QoL by two instruments: EUROQOL and the European Organisation
      for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire
      (QLQ)-C30. RESULTS: Baseline malnutrition was prevalent in HR vs. LR (P=0.02);
      nutritional intake was associated with nutritional status (P=0.007); the latter
      did not change significantly during RT. In LR, baseline energy intake was higher
      than EER (P=0.001), and higher than HR' intake (P=0.002); the latter increased
      (P<0.03), in spite of symptom increase anew and/or in severity (P=0.0001).
      According to both instruments, QoL was always better in LR vs. HR (P=0.01); at
      the end of RT, QoL improvement in HR was correlated with increased nutritional
      intake (P=0.001), both remained stable in LR. CONCLUSIONS: Individualised
      nutritional counselling accounting for nutritional status and clinical condition,
      was able to improve nutritional intake and patients' QoL, despite self-reported
      symptoms.

PMID- 12812854
TI  - Palliative radiotherapy for patients with bone metastases: survey of primary care
      physicians.
AB  - Three hundred Canadian primary care physicians were surveyed to determine their
      perceived barriers to the accessibility of palliative bone radiotherapy and their
      perceptions regarding treatment efficacy. The response rate was 61%. Factors
      perceived to hinder accessibility were identified, and the physicians recognized
      they were not comfortable with their radiotherapy knowledge.

PMID- 12812855
TI  - A widely tested model for head scatter influence on photon beam output.
AB  - PURPOSE: To construct and test a semi-analytical model describing the effects on
      Monitor Unit (MU) verification caused by scattering in the treatment head. The
      implementation of the model should be accomplished using a small set of
      experimental data. Furthermore, the model should include a geometry dependent
      estimation of the resulting uncertainty. MATERIAL AND METHODS: The input required
      by the created model consists of basic treatment head geometry and 10 measured
      output factors in air (OFair) for square fields. It considers primary energy
      fluence, scattered radiation from an extra-focal source and from secondary
      collimators, as well as backscatter to the monitor chamber. Measurements and
      calculations were performed in open symmetric and asymmetric fields at points
      located both on and off the collimator axis, as well as at arbitrary treatment
      distances. The model has been verified for 19 photon beams in the range from 4 up
      to 50 MV, provided by nine different treatment units from six manufacturers.
      RESULTS: The presented model provided results with errors smaller than 1% (2
      S.D.) in typical clinical situations for all beams tested. In more exceptional
      situations, i.e. combinations of unconventional treatment head designs, very
      elongated fields, and dosimetry points far away from the isocenter, the total
      uncertainty increased to approximately 2%. The spread in the results was further
      analysed in order to create a method for predicting the uncertainties under
      different treatment conditions. CONCLUSIONS: A general head scatter model that is
      easy to implement has been developed and can be used as the basis for
      computerised MU verification. The model handles all commercially available
      treatment units adequately and also includes an estimation of the resulting
      uncertainty.

PMID- 12812856
TI  - Experimental validation tests of fast Fourier transform convolution and multigrid
      superposition algorithms for dose calculation in low-density media.
AB  - BACKGROUND AND PURPOSE: Modern conformal radiotherapy treatments require accurate
      dose calculation in any relevant clinical situation. One of these situations is
      the treatment of lung tumors, where irradiation has to be planned under
      challenging conditions for dose calculation. In this study we assess the errors
      in dose values predicted by fast Fourier transform convolution (FFTC) and
      multigrid superposition (MGS) algorithms implemented in a commercial treatment
      planning system (TPS). MATERIALS AND METHODS: FFTC and MGS algorithms were used
      in a FOCUS 3.0.0 (Computerized Medical Systems, USA) to calculate doses in
      treatment plans using photon beams of 6 and 25 MV nominal energy from a Saturne
      43 linac (GE Medical Systems, USA). A 10x10-cm beam irradiating a mediastinum
      lung and a thoracic wall-lung-thoracic wall modeled geometry was assessed. The
      calculated data were compared with measurements performed with radiographic films
      and ionization chamber. RESULTS: FFTC algorithm leads to an average deviation
      from ionometric dose measurements of over 10%. Discrepancies between measured and
      calculated beam fringe values (distance between 50 and 90% isodose lines) of up
      to 8 mm were observed. For MGS algorithm, all the points assessed in both
      geometries fulfilled the 3%-3 mm accuracy criteria and the average deviation of
      absolute dose was about 1%. A maximum of 3 mm deviation in the beam fringe for
      any depth was found and was within 2 mm beyond the buildup region. Deviations
      between ionometric and film measurements were within 3%. CONCLUSIONS: MGS
      algorithm assesses with reasonable accuracy dose distributions and absolute dose
      in inhomogeneous regions like the lung region. Therefore, and respecting the
      inhomogeneity dose calculation, the system could be used in routine clinical
      practice and in dose-escalation programs. This is not true in the case of FFTC
      algorithm which leads to errors greater than 10% in the absolute dose calculation
      and underestimates the beam fringe by up to 8 mm.

PMID- 12812857
TI  - Apropos the "International consensus on palliative radiotherapy endpoints for
      future clinical trials in bone metastases".

PMID- 12812859
TI  - Re: "In vivo determination of extra-target doses received from serial
      tomography".

PMID- 12812860
TI  - Systemic apomorphine alters HPA axis responses to interleukin-1 beta
      administration but not sound stress.
AB  - Apomorphine is a dopamine receptor agonist that was recently licensed for the
      treatment of erectile dysfunction. However, although sexual activity can be
      stressful, there has been little investigation into whether treatments for
      erectile dysfunction affect stress responses. We have examined whether a single
      dose of apomorphine, sufficient to produce penile erections (50 microg/kg, i.a.),
      can alter basal or stress-induced plasma ACTH levels, or activity of central
      pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An
      immune challenge (interleukin-1 beta, 1 microg/kg, i.a.) was used as a physical
      stressor while sound stress (100 dB white noise, 30 min) was used as a
      psychological stressor. Intravascular administration of apomorphine had no effect
      on basal ACTH levels but did substantially increase the number of Fos-positive
      amygdala and nucleus tractus solitarius catecholamine cells. Administration of
      apomorphine prior to immune challenge augmented the normal ACTH response to this
      stressor at 90 min and there was a corresponding increase in the number of Fos
      positive paraventricular nucleus corticotropin-releasing factor cells,
      paraventricular nucleus oxytocin cells and nucleus tractus solitarius
      catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos
      responses to sound stress. These data suggest that erection-inducing levels of
      apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory
      feedback mechanisms in response to a physical stressor, but have no effect on the
      response to a psychological stressor. Consequently, it is likely that apomorphine
      acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to
      physical stressors. A candidate for this site of action is the nucleus tractus
      solitarius catecholamine cell population and, in particular, A2 noradrenergic
      neurons.

PMID- 12812862
TI  - Estrogen fluctuations, oral contraceptives and borderline personality.
AB  - Results from three studies suggest fluctuation in estrogen level may influence
      the expression of borderline personality disorder (BPD) symptoms. In the first
      study, 226 women were administered the Personality Assessment Inventory,
      borderline scales (PAI-BOR; L.C. Morey, The Personality Assessment Inventory,
      Professional Manual, 1991) and a questionnaire that assessed time in menstrual
      cycle and use of oral contraceptives, that is synthetic estrogens. BPD symptoms
      were most common in women using oral contraceptives and during times in the
      menstrual cycle when estrogen level is rising. In Study 2, 52 women were measured
      four times across one menstrual cycle and provided salivary samples at each test
      session. The samples were assayed and estrogen levels were obtained. The
      principle finding was that variation in estrogen levels predicted the presence of
      BPD symptoms (r=0.4, p<0.01). This relationship remained significant when a
      general increase in negative affect was statistically controlled. Study 3
      employed a pre-post Oral Contraceptive (OC) design with a control group. It was
      found that for women with high pre-existing levels of BPD, symptoms became
      significantly worse after starting pill use (F (3,42)=4.7; p<0.01). Research
      findings that link the serotonin system and estrogen are reviewed and theoretical
      and practical implications are discussed.

PMID- 12812861
TI  - Cortisol response to a cognitive stress challenge in posttraumatic stress
      disorder (PTSD) related to childhood abuse.
AB  - Preclinical studies show that animals with a history of chronic stress exposure
      have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following
      reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have
      been found to have normal or decreased function of the HPA axis, however no
      studies have looked at the HPA response to stress in PTSD. The purpose of this
      study was to assess cortisol responsivity to a stressful cognitive challenge in
      patients with PTSD related to childhood abuse. Salivary cortisol levels, as well
      as heart rate and blood pressure, were measured before and after a stressful
      cognitive challenge in patients with abuse-related PTSD (N=23) and healthy
      comparison subjects (N=18). PTSD patients had 61% higher group mean cortisol
      levels in the time period leading up to the cognitive challenge, and 46% higher
      cortisol levels during the time period of the cognitive challenge, compared to
      controls. Both PTSD patients and controls had a similar 66-68% increase in
      cortisol levels from their own baseline with the cognitive challenge. Following
      the cognitive challenge, cortisol levels fell in both groups and were similar in
      PTSD and control groups. PTSD patients appeared to have an increased cortisol
      response in anticipation of a cognitive challenge relative to controls. Although
      cortisol has been found to be low at baseline, there does not appear to be an
      impairment in cortisol response to stressors in PTSD.

PMID- 12812863
TI  - Randomized controlled evaluation of the effects of cognitive-behavioral stress
      management on cortisol responses to acute stress in healthy subjects.
AB  - Psychosocial stress is a potent activator of the hypothalamus-pituitary-adrenal
      (HPA) axis. While neuroendocrine stress responses are essential for the
      maintenance of homeostasis, evidence suggests that excessive activation of the
      HPA axis constitutes a risk for disease and psychopathology. The purpose of the
      present study was to assess the effect of cognitive-behavioral stress management
      training on endocrine stress responses and cognitive appraisal under acute
      psychosocial stress among healthy young subjects. Forty-eight healthy, non
      smoking male students without acute or chronic medical or psychiatric disorder on
      self report were randomly assigned to receive group-based cognitive-behavioral
      stress management training either before or after a standardized psychosocial
      stress test (Trier Social Stress Test, TSST). Endocrine and psychological stress
      responses were assessed with salivary free cortisol response and cognitive
      appraisal processes to the TSST. In comparison with the control group, subjects
      in the treatment group showed an attenuated endocrine response (F (2.55/117.41) =
      3.81; P = 0.02; effect size f(2) = 0.35) to the TSST. In addition, subjects in
      the SIT group had lower stress appraisal and higher control expectancies (F
      (2/45) = 6.56; P = 0.003, effect size f(2) = 0.29) compared to controls. Short
      group-based cognitive-behavioral stress management training reduces the
      neuroendocrine stress response to an acute stressor in healthy subjects.
      Therefore, stress management training may prove useful in preventing detrimental
      effects of stress-induced neuroendocrine activation

PMID- 12812864
TI  - Depression-like changes of the sleep-EEG during high dose corticosteroid
      treatment in patients with multiple sclerosis.
AB  - Acute exacerbations of multiple sclerosis (MS) are commonly treated with high
      doses of corticosteroids that can influence sleep regulation and hypothalamo
      pituitary-adrenal (HPA) activity. We examined the sleep-EEG (including
      conventional and spectral EEG analysis) in 9 female patients with relapsing
      remitting MS (and no psychiatric disorder) just prior to and on days 2 and 10 of
      high dose corticosteroid treatment (500 mg/day methylprednisolone given IV for 5
      days, then PO taper down) and age-matched healthy female controls. Before
      treatment with corticosteroids, MS patients compared to controls showed few
      changes of the sleep EEG, namely a significant increase in slow wave sleep (SWS)
      and a decrease in stage 2 sleep. In contrast, on day 10, but not day 2 of
      treatment, MS patients showed a number of sleep-EEG changes typically observed in
      patients with depression, including a reduction in REM latency, an increase in
      REM density, a decrease in the SWS and delta sleep ratio and a decrease in sigma
      EEG activity. However, no concomitant effect of treatment on mood was noted. In
      summary, unlike acute treatment with methylprednisolone, prolonged treatment
      induces several changes of the sleep-EEG in MS patients, that are also observed
      in patients with an acute depressive episode. Further prospective studies with
      longer-term follow-up are needed to examine the clinical relevance of our
      preliminary data.

PMID- 12812865
TI  - Plasma cortisol and neuropeptide Y in female victims of intimate partner
      violence.
AB  - BACKGROUND: The experience of intimate partner violence (physical and sexual
      violence) has been linked to psychiatric disorders such as posttraumatic stress
      disorder, yet data on the neuroendocrine profile in this population is sparse.
      This study sought to examine baseline plasma cortisol and neuropeptide Y (NPY)
      levels in female victims of intimate partner violence (IPV). METHODS: Morning
      plasma samples were collected for cortisol and NPY determination in 22 women with
      histories of IPV (10 with current PTSD, 12 without current or lifetime PTSD) and
      16 non-abused controls. RESULTS: Mean cortisol levels were significantly lower in
      IPV subjects compared with controls, but did not distinguish IPV subjects with
      and without PTSD. There were no significant differences in mean NPY levels
      between the groups. Neither cortisol nor NPY levels were significantly correlated
      with PTSD symptoms. CONCLUSIONS: These preliminary findings suggest that victims
      of IPV, like women traumatized by childhood abuse, may be characterized by
      alterations in hypothalamic-pituitary-adrenal axis functioning, however, further
      study is needed to identify specific stress system disturbances in this group.

PMID- 12812866
TI  - Insulin dose-response effects on memory and plasma amyloid precursor protein in
      Alzheimer's disease: interactions with apolipoprotein E genotype.
AB  - In previous studies, adults with Alzheimer's disease (AD) showed memory
      enhancement when plasma insulin levels were raised to 85 microU/ml, whereas
      normal adults' memory was unchanged. Degree of memory enhancement was also
      related to apolipoprotein E (apoE) genotype status for AD patients. Response
      differences between normal and AD groups could reflect dose-response differences
      for insulin. To examine this question, 22 adults with AD and 15 normal adults
      received five doses of insulin on separate days in counterbalanced order,
      resulting in five plasma insulin levels (10, 25, 35, 85 and 135 microU/ml), while
      plasma glucose levels of ~100 mg/dl were maintained. Cognitive performance and
      plasma APP levels were measured after 120 min of infusion. Relative to baseline,
      AD patients who were not apoE- epsilon 4 homozygotes had improved memory at
      higher insulin levels of 35 and 85 microuU/ml, whereas normal adults and AD
      patients who were epsilon 4 homozygotes showed improved memory at insulin levels
      of 25 microU/ml. Normal adults' memory was also improved at insulin levels of 85
      microU/ml. Plasma APP was lowered for adults with AD without the epsilon 4 allele
      at higher levels (85 microU/ml) than for normal adults and epsilon 4 homozygotes,
      who showed decreased APP at the 35 microU/ml level. AD patients with a single
      epsilon 4 allele showed a different pattern of insulin effects on APP than did
      other subjects. In general, few effects of insulin were seen at the highest dose
      for any subject group. These results support a role for insulin in normal memory
      and APP modulation that follows a curvilinear response pattern, and suggest that
      AD patients who are not epsilon 4 homozygotes have reduced sensitivity to insulin
      that may interfere with such modulation.

PMID- 12812869
TI  - A well armed predator.

PMID- 12812870
TI  - Microbial keratitis.

PMID- 12812871
TI  - Does human papillomavirus cause pterygium?

PMID- 12812872
TI  - Responding to readers' and authors' needs.

PMID- 12812873
TI  - Effects of air pollution and climatic conditions on the frequency of
      ophthalmological emergency examinations.

PMID- 12812874
TI  - Outcomes of cataract surgery in Bangladesh: results from a population based
      nationwide survey.
AB  - AIM: To evaluate the outcome of cataract surgery in the population of Bangladesh.
      METHODS: Data were collected by the National Blindness and Low Vision Prevalence
      Survey of Bangladesh, a cross sectional, nationally representative sample (12 782
      subjects) of the population aged >or=30 years. An interview recorded
      socioeconomic data. Each subject was tested for logMAR visual acuity (VA) of each
      eye, autorefracted, and then underwent optic disc examination. Those with <6/12
      VA on presentation in either eye were retested with their refractive correction,
      dilated, and examined for anterior and posterior segment disease. In aphakic and
      pseudophakic subjects the date, location and operating conditions (eye
      camp/hospital), and type of operation(s) were recorded. RESULTS: 11 624 eligible
      subjects were examined (90.9% response rate) in the survey. 162 subjects, 77 men
      and 85 women, had undergone cataract surgery in one or both eyes. 199 (88%) eyes
      had undergone intracapsular cataract extraction (ICCE), and 22 (10%)
      extracapsular surgery with intraocular lens (ECCE+IOL); surgical technique(s) in
      four cases were not identified. Presenting VA for the 226 operated eyes were: 68
      eyes (30.1%) were 6/12 or better, 31 (13.7%) <6/12 >or=6/18, 63 (27.9%) 6/18 to
      6/60, 8 (3.5%) <6/60 >or=3/60, and 56 (24.8%) <3/60. With "best" refractive
      correction these values were 114 (50.4%), 31 (13.7%), 51 (22.6%), 5 (2.2%), and
      25 (11.1%), respectively. Of the 158 eyes with VA of 6/12 or worse on
      presentation, 44 (28%) were the result of coincident disease (principally age
      related macular degeneration), 95 (60%) refractive error (44 of these had
      uncorrected aphakia), and 19 (12%) operative complications. ICCE was more likely
      to result in a VA of <6/18 (OR: 4.26, p = 0.01) than ECCE+IOL. Likewise, eye camp
      surgery was more likely to result in a VA of <6/60 (OR: 1.98, p = 0.04). No
      significant association was found between time since surgery and VA outcome, nor
      was there a sex difference for postoperative vision. Literate subjects were
      significantly less likely to have an outcome of <6/18 (OR: 2.38, p <0.01) or
      <6/60 (OR: 2.87, p <0.01). Following ICCE (199 eyes), 56 (37%) of the 151 eyes
      with an aphakic spectacle correction achieved 6/12 or better. Females, eye camp
      surgeries, illiterate subjects, and rural dwellers were less likely to wear their
      aphakic correction. The ratio of ICCE:ECCE+IOL has reduced in the past 3 years
      (3.8:1) compared to >or=4 years before the survey (25:1). Hospital based ECCE+IOL
      surgeries were associated with a better outcome, yet 36% of these eyes were <6/12
      postoperatively, after excluding coincident disease. CONCLUSION: This evaluative
      research study into cataract surgery outcomes in Bangladesh highlights the need
      for an improvement in quality and increased quantity of surgery with a more
      balanced distribution of services.

PMID- 12812875
TI  - Prevalence and causes of blindness and visual impairment in Bangladeshi adults:
      results of the National Blindness and Low Vision Survey of Bangladesh.
AB  - AIM: To determine the age, sex, and cause specific prevalences of blindness and
      visual impairment in adults 30 years of age and older in Bangladesh. METHODS: A
      nationally representative sample of 12 782 adults 30 years of age and older was
      selected based on multistage, cluster random sampling with probability
      proportional to size procedures. The breakdown of the cluster sites was
      proportional to the rural/urban distribution of the national population. The
      examination protocol consisted of an interview, visual acuity (VA) testing,
      autorefraction, and optic disc examination on all subjects. Corrected VA
      retesting, cataract grading, and a dilated fundal examination were performed on
      all visually impaired subjects. The definitions of blindness (<3/60) and low
      vision (<6/12 to >or=3/60) were based on the presenting visual acuity in the
      better eye. The World Health Organization/Prevention of Blindness proforma and
      its classification system for identifying the main cause of low vision and
      blindness for each examined subject was used. RESULTS: In total, 11 624 eligible
      subjects were examined (90.9% response rate) across the 154 cluster sites. A
      total of 162 people were bilaterally blind (1.53% age standardised prevalence)
      while a further 1608 subjects (13.8%) had low vision (<6/12 VA) binocularly.
      Visual acuity was >6/12 in the "better eye" in the remaining 9854 subjects
      (84.8%); however, 748 of these people had low vision in the fellow eye. The main
      causes of low vision were cataract (74.2%), refractive error (18.7%), and macular
      degeneration (1.9%). Cataract was the predominant cause (79.6%) of bilateral
      blindness followed by uncorrected aphakia (6.2%) and macular degeneration (3.1%).
      CONCLUSIONS: There are an estimated 650 000 blind adults (95% CI 552 175 to 740
      736) aged 30 and over in Bangladesh, the large majority of whom are suffering
      from operable cataract. This survey indicates the need for the development and
      implementation of a national plan for the delivery of effective eye care
      services, aimed principally at resolving the large cataract backlog and the
      inordinate burden of refractive error.

PMID- 12812876
TI  - Incidence of visual loss in rural southwest Uganda.
AB  - BACKGROUND: Surveys have been conducted to measure prevalence of eye disease in
      Africa, but not of incidence, which is needed to forecast trends. The incidence
      of visual loss is reported in southwest Uganda. METHODS: A rural population
      residing in 15 neighbouring villages was followed between 1994-5 (R1) and 1997-8
      (R2). Survey staff screened adult residents (13 years or older) for visual acuity
      using laminated Snellen's E optotype cards at each survey. Those who failed (VA
      >6/18) were evaluated by an ophthalmic clinical officer and an ophthalmologist.
      Incidence of visual loss (per 1000 person years (PY)) was calculated among those
      who had normal vision at R1. RESULTS: 2124 people were studied at both survey
      rounds (60.9% of those screened at R1); 48% were male. Participants in R1 were
      older (34.7 versus 31.5 years at R2, p<0.001). Visual loss in R2 occurred in 56
      (2.8%) of 1997, yielding a crude incidence rate of 9.9, and an age standardised
      incidence rate of 13.2, per 1000 PY. Incidence of visual loss increased with age
      from 1.21 per 1000 PY among people aged 13-34 to 64.2 per 1000 PY in those aged
      65 years or older (p for trend >0.001). The six commonest causes of visual loss
      were: cataract, refractive error, macular degeneration, chorioretinitis,
      glaucoma, and corneal opacity. If similar rates are assumed for the whole of
      Uganda, it is estimated that 30 348 people would develop bilateral blindness or
      bilateral visual impairment, per year. CONCLUSIONS: Cataract and refractive error
      were the major causes of incident visual loss in south west Uganda. These data
      are valuable for forecasting and planning eye services.

PMID- 12812878
TI  - Bacterial keratitis: predisposing factors, clinical and microbiological review of
      300 cases.
AB  - AIM: To identify predisposing factors and to define clinical and microbiological
      characteristics of bacterial keratitis in current practice. METHODS: A
      retrospective analysis of the hospital records of patients presenting with
      bacterial keratitis and treated at the Quinze-Vingts National Center of
      Ophthalmology, Paris, France, was performed during a 20 month period. A bacterial
      keratitis was defined as a suppurative corneal infiltrate and overlying
      epithelial defect associated with presence of bacteria on corneal scraping and/or
      that was cured with antibiotic therapy. Risk factors, clinical and
      microbiological data were collected. RESULTS: 300 cases (291 patients) of
      presumed bacterial keratitis were included. Potential predisposing factors,
      usually multiple, were identified in 90.6% of cases. Contact lens wear was the
      main risk factor (50.3%). Trauma or a history of keratopathy was found in 15% and
      21% of cases, respectively. An organism was identified in 201 eyes (68%). 83% of
      the infections involved Gram positive bacteria, 17% involved Gram negative
      bacteria, and 2% were polymicrobial. Gram negative bacteria were associated with
      severe anterior chamber inflammation (p=0.004), as well as greater surface of
      infiltrates (p=0.01). 99% of ulcers resolved with treatment, but only 60% of
      patients had visual acuity better than the level at admission, and 5% had very
      poor visual outcome. CONCLUSIONS: Contact lens wear is the most important risk
      factor. Most community acquired bacterial ulcers resolve with appropriate
      treatment.

PMID- 12812879
TI  - A clinical, histopathological, and genetic study of Avellino corneal dystrophy in
      British families.
AB  - AIMS: To establish a clinical, histopathological, and genetic diagnosis in two
      unrelated British families with Avellino corneal dystrophy (ACD). METHODS:
      Genomic DNA was extracted from peripheral blood leucocytes of all members
      participating in the study. Exons 4 and 12 of the human transforming growth
      factor beta induced (BIGH3) gene were amplified by polymerase chain reaction. The
      mutation and polymorphism were identified by direct sequencing and restriction
      digest analysis. A review of the patients' clinical symptoms and signs was
      undertaken and a histopathological study on corneal specimen obtained from the
      proband of one family after keratoplasty was performed. RESULTS: A heterozygous G
      to A transition at the second nucleotide position of codon 124 of BIGH3 gene was
      detected in all affected members of both families. This mutation changes an
      arginine residue to a histidine. The clinical diagnosis for ACD was more evident
      with advancing age. Histopathological study revealed granular deposits in the
      anterior stroma and occasional positive Congo red areas of amyloid deposition in
      the mid to deep stroma typical of ACD. CONCLUSIONS: This is the first report of
      ACD families in the United Kingdom and, furthermore, of BIGH3 gene mutation in
      British patients with this rare type of corneal dystrophy. The results indicate
      that BIGH3 gene screening along with clinical and histopathological examinations
      is essential for the diagnosis and clinical management of corneal dystrophies.

PMID- 12812880
TI  - Is manual small incision cataract surgery affordable in the developing countries?
      A cost comparison with extracapsular cataract extraction.
AB  - AIM: To compare the cost of manual small incision cataract surgery (MSICS) with
      conventional extracapsular cataract surgery (ECCE) in community eye care
      settings. METHOD: A single masked randomised trial was used to compare the
      safety, efficacy, time, and patient satisfaction of surgery by both the
      techniques. The fixed facility and recurrent cost for the two procedures was
      calculated based on information collected from different sources. Average cost
      per procedure was calculated by dividing the total cost by the number of
      procedures performed. RESULT: The average cost of an ECCE procedure for the
      hospital was Rs 727.76 (US$15.82) and the average cost of a MSICS procedure was
      Rs 721.40 ($15.68), of which Rs. 521.51 ($11.34) was the fixed facility cost
      common to both. CONCLUSION: Both ECCE and MSICS are economical in community eye
      care settings, but MSICS is economical and gives better uncorrected visual acuity
      in a greater proportion of patients.

PMID- 12812882
TI  - Sex inequalities in cataract blindness burden and surgical services in south
      India.
AB  - AIM: To determine sex inequalities in cataract blindness and surgical services in
      south India. METHODS: Details of lens status and cataract surgery were recorded
      for subjects aged 50 years and older identified through cluster sampling as part
      of population based cross sectional assessments of cataract blindness and
      surgical outcomes in three districts of south India. RESULTS: Females were less
      likely to be operated on for cataract (adjusted OR 0.71, 95% CI: 0.57 to 0.87)
      although the cataract blindness burden was higher for females (p<0.001). Literacy
      of the subject was a major predictor for being operated on for cataract.
      Achieving equal surgical coverage between sexes will have resulted in an
      additional 25.3% reduction of cataract blindness. CONCLUSIONS: Eye care
      programmes in this population need to be sensitised to the substantial reduction
      in blindness possible by achieving equal surgical coverage between sexes.

PMID- 12812883
TI  - Long term effect on intraocular pressure of phacotrabeculectomy compared to
      trabeculectomy.
AB  - AIM: To compare the long term mean intraocular pressure (IOP) reduction after non
      augmented single site phacotrabeculectomy with that after trabeculectomy and to
      determine the relation between preoperative IOP and IOP reduction. METHODS: A
      group of 44 consecutive patients with chronic open angle glaucoma who underwent
      phacotrabeculectomy were matched to a trabeculectomy control group and the
      results of surgery were compared. Linear regression analysis of preoperative IOP
      and IOP reduction was undertaken. RESULTS: The mean IOP reduction was
      significantly less in the phacotrabeculectomy group (6.7 (SD 2.1) mm Hg) than in
      the trabeculectomy group (11.0 (1.4) mm Hg) (p=0.0017). There was a significant
      difference in surgical success between the groups. The preoperative IOP was
      significantly related to the postoperative reduction in IOP in both groups
      (p<0.001). CONCLUSIONS: In elderly white patients with chronic open angle
      glaucoma, phacotrabeculectomy is not as effective as trabeculectomy in reducing
      IOP. In both procedures the magnitude of IOP reduction is proportional to the
      preoperative IOP.

PMID- 12812884
TI  - Long term visual outcome of patients with cytomegalovirus retinitis treated with
      highly active antiretroviral therapy.
AB  - BACKGROUND: Healed cytomegalovirus (CMV) retinitis in the setting of highly
      active antiretroviral therapy (HAART) is complicated by inflammatory sequelae and
      vision loss. AIM: To determine the long term visual outcome of AIDS patients with
      CMV retinitis who received HAART. METHODS: 90 eyes of 63 consecutive AIDS
      patients with extramacular CMV retinitis were studied prospectively. RESULTS:
      Immune recovery status was related to time to onset of epiretinal membrane
      (p=0.05) and cystoid macular oedema (p=0.06) as well as to the incidence of
      cataract (p=0.001) and moderate vision loss (p<0.0001). Severe vision loss was
      associated with retinal detachment (p<0.001). CONCLUSION: AIDS patients with
      extramacular CMV retinitis lose vision while on HAART. HAART related immune
      recovery is associated with increased frequencies of epiretinal membrane, cystoid
      macular oedema, cataract, and retinal detachment with resultant vision loss in
      AIDS patients with healed CMV retinitis.

PMID- 12812885
TI  - Subretinal fibrosis after photodynamic therapy in subfoveal choroidal
      neovascularisation in highly myopic eyes.
AB  - AIMS: To analyse the occurrence of subretinal fibrosis (SRF) after photodynamic
      therapy (PDT) with verteporfin in highly myopic eyes with subfoveal choroidal
      neovascularisation (CNV). METHODS: PDT with verteporfin was performed on 33 eyes
      of 32 highly myopic patients with subfoveal CNV. Patients were followed for 14-24
      months and best corrected visual acuity (BCVA) and angiographic and funduscopic
      findings were recorded. RESULTS: Two patients (two eyes) were lost to follow up.
      SRF appeared in 14 of 31 eyes. SRF appeared more frequently in eyes with a
      spherical equivalent (SE) of less than -10 D, in patients of age equal to or less
      than 55 years, and when CNVs were larger than 1500 micro m in diameter. SRF
      appeared more frequently in the group of patients with worse final BCVA.
      CONCLUSIONS: The appearance of SRF after treatment is correlated with size of the
      CNV and SE. The results of this study indicate that highly myopic eyes with CNV
      treated with PDT do not show a decrease in BCVA, even though they develop SRF.
      The appearance of SRF after PDT in highly myopic CNV does not always imply a loss
      of BCVA from baseline, though its presence is more frequent in eyes with lower
      BCVA.

PMID- 12812886
TI  - The management of orbital cysts associated with congenital microphthalmos and
      anophthalmos.
AB  - AIMS: To study the management of the orbital cysts present in a group of patients
      with anophthalmos and microphthalmos. METHODS: A retrospective study of 34
      patients (40 orbits) treated for orbital cyst associated with microphthalmos and
      anophthalmos. RESULTS: The two largest treatment groups comprised 17 orbits
      (42.5%) where the cyst was removed surgically and 17 orbits (42.5%) where the
      cyst was retained and conformers were used. The remaining cases comprised two
      orbits (5%) where the cyst was aspirated initially; two orbits (5%) with large
      cysts which will need to be excised after further orbital growth; one orbit
      (2.5%) in which a silicone expander was used initially, and one orbit (2.5%) in
      which a mildly microphthalmic eye had some vision and was monitored but required
      no surgery. CONCLUSION: In this study 33 out of 34 patients had a good cosmetic
      result which illustrates that the orbital cyst in microphthalmos or anophthalmos
      performs a useful role in socket expansion and that the majority of patients with
      this condition can expect a good cosmetic outcome.

PMID- 12812887
TI  - Detection of human papillomavirus DNA in pterygia from different geographical
      regions.
AB  - BACKGROUND/AIMS: The aetiology and pathogenesis of pterygia remain unclear and
      the involvement of human papillomavirus (HPV) is controversial. 41 pterygia from
      two geographic locations were evaluated for the presence of HPV DNA. METHODS: 41
      pterygium biopsies (17 from Italy and 24 from Ecuador) were analysed using the
      L1C1 and PU-1ML primer sets by polymerase chain reaction (PCR) and DNA sequence
      analysis. RESULTS: 22 of the 41 pterygia (54%) were positive for HPV, including
      all 17 Italian cases and 5/24 (21%) Ecuadorean cases. DNA sequencing of the 22
      positive cases showed that 11 were HPV type 52, four were type 54, five were
      candHPV90, and two of unknown genotype. CONCLUSIONS: The major differences in the
      frequency of HPV in geographically distant populations might suggest a possible
      explanation for the vast differences in the reported detection rates. Three
      subtypes of HPV were found in this sample of pterygia. None the less, these
      results suggest that HPV may have a pathogenic role in pterygium.

PMID- 12812888
TI  - A 10 year retrospective survey of cataract surgery and endophthalmitis in a
      single eye unit: injectable lenses lower the incidence of endophthalmitis.
AB  - AIM: To study the incidence of endophthalmitis following cataract surgery over a
      10 year period, and to examine ways in which this may be related to changes in
      surgical technique. METHODS: All cases of endophthalmitis occurring over a 10
      year period within a single ophthalmic unit in the United Kingdom were reviewed,
      and possible risk factors identified. RESULTS: During the study period, as the
      technique of extracapsular cataract surgery was replaced by phacoemulsification,
      there was a commensurate reduction in the incidence of endophthalmitis.
      Injectable IOLs were associated with the lowest risk of postoperative
      endophthalmitis (0.028%). CONCLUSIONS: Injectable intraocular lenses do not make
      contact with the ocular surface and this may result in the observed lower rate of
      endophthalmitis. This, and the ease with which they can be inserted through small
      incisions, support their use as the first line method of lens insertion.

PMID- 12812889
TI  - Photodynamic modulation of wound healing in glaucoma filtration surgery.
AB  - AIM: To report a clinical pilot study investigating photodynamic therapy (PDT) in
      combination with glaucoma filtration surgery. BCECF-AM was used as the
      photosensitising substance. The clinical safety and tolerability of BCECF-AM, and
      its efficacy in controlling postoperative intraocular pressure (IOP) were
      assessed. METHODS: Before trabeculectomy (TE), 42 consecutive eyes of 36 glaucoma
      patients received one subconjunctival injection of 80 micro g BCECF-AM (2,7,-bis-
      (2-carboxyethyl) -5- (and-6) -carboxy-fluorescein, acetoxymethyl-ester) followed
      by an intraoperative illumination with blue light (lambda = 450-490 nm) for 8
      minutes. Antifibrotic efficacy was established as postoperative IOP reduction of
      >20% and/or an IOP constantly < 21 mm Hg without antiglaucomatous medication.
      Follow up of the filtering bleb was documented by slit lamp examination. RESULTS:
      Eyes had mean 1.1 preoperative surgical interventions (filtration and non
      filtration glaucoma surgery). Mean preoperative IOP was 31.6 (SD 9.7) mm Hg.
      Patients were followed for mean 496 days (range 3.5-31.8 months). Of the 42 eyes,
      25 eyes had an IOP decreased to 15.8 (3.4) mm Hg without medication (complete
      success: 59.5%; p<0.001; t test). Seven eyes showed good IOP reduction < 21 mm Hg
      under topical antiglaucomatous medication (qualified success: 16.7%). 10 eyes
      failed because of scarring within 2-67 weeks (23.8%). Clinical follow up
      examinations revealed no local toxicity, no uveitis, and no endophthalmitis.
      CONCLUSIONS: This method is a new approach in modulating postoperative wound
      healing in human eyes undergoing glaucoma filtration surgery. The data of the
      first human eyes combining TE with PDT underline the clinical safety of this
      method and its possible potential to prolong bleb survival.

PMID- 12812890
TI  - Behcet's disease in patients of west African and Afro-Caribbean origin.
AB  - AIM: To report the presence of Behcet's disease with ocular involvement in
      patients of west African or Afro-Caribbean origin. METHODS: Case series of eight
      patients reporting to a tertiary uveitis service. RESULTS: Eight patients with
      typical features of the disease are presented. Six of the eight patients were
      tested and found to be HLA-B51 negative. CONCLUSION: Behcet's disease has only
      been reported in sporadic case reports in the indigenous west African and Afro
      Caribbean populations, in whom the incidence of HLA B51 is also very low. A
      series of patients from the London region presented with the typical symptoms and
      signs of disease, most of whom were also HLA B51 negative. The presence of
      disease in this population, when absent in the indigenous population, suggests
      either that ascertainment of disease is poor in the indigenous population or that
      acquired factors may be important in the aetiology of the disease.

PMID- 12812891
TI  - Visual loss in uveitis of childhood.
AB  - AIMS: To investigate the manifestations and severity of uveitis in children and
      to identify the risk and specific causes of blindness in this population.
      METHODS: Retrospective study of data of 123 consecutive patients examined with
      active uveitis and the onset of ocular disease before the age of 16 years.
      Numerous variables were assessed including age and sex distribution, laboratory
      data, the presence of systemic diseases, onset and course of ocular inflammation,
      clinical features and complications, therapeutic strategies and their outcomes,
      final visual acuity, and characteristics associated with poor visual outcome.
      RESULTS: Systemic disease was observed in 36/123 patients (29%), with juvenile
      idiopathic arthritis being the most frequent (25/123, 20%). Toxoplasma
      retinochoroiditis was diagnosed in 12/23 patients with posterior uveitis (52%;
      10% of all with uveitis). Severe intraocular inflammation required systemic drugs
      in 57 (46%) patients. Ocular complications were observed in 93 patients (76%), of
      which the most common was cataract (43/123, 35%). Intraocular surgery was
      required in 35 patients (28%; in total 75 procedures). Three patients (2%) became
      legally blind and an additional 20/121 (17%) had one legally blind eye caused by
      uveitis. The most frequent causes of blindness were chorioretinal scars in the
      macular area and glaucoma in contrast with cystoid macular oedema (CMO) in
      adults. CONCLUSIONS: Uveitis in childhood is a potentially blinding disease, in
      the majority of patients characterised by a chronic course and a high
      complication rate.

PMID- 12812892
TI  - Internal limiting membrane removal in macular hole surgery for severely myopic
      eyes: a case-control study.
AB  - AIMS: To determine the surgical outcome of indocyanine green (ICG) assisted
      retinal internal limiting membrane (ILM) peeling in macular hole surgery for
      severely myopic eyes and compare the visual and anatomical outcomes with an
      emmetropic control group. METHODS: 10 severely myopic eyes (-6.0 D or greater) of
      10 patients with macular holes without retinal detachment were recruited
      prospectively. All eyes received ICG assisted ILM removal of 3-4 disc diameters
      around the macular holes. Cases were matched with a prospective control group of
      10 emmetropic macular hole patients who underwent identical ICG assisted ILM
      peeling surgery in the same period. RESULTS: The mean refractive error in the
      myopic and control group was -11.8 D and +0.3 D, respectively (two tailed t test,
      p < 0.001). The mean follow up duration for the myopic and control group was 12.1
      and 13.3 months, respectively (two tailed t test, p = 0.63). The primary
      anatomical closure rate in both groups was 90% (Fisher's exact test, p = 1.0).
      For both the myopic and control groups, there were significant improvement in the
      mean log MAR visual acuity after the surgery with improvements from 0.86 to 0.57
      for the myopic group (two tailed t test, p = 0.015) and 0.89 to 0.44 for the
      control group (two tailed t test, p = 0.002). The mean preoperative and
      postoperative visual acuity, rates of final visual acuity of 20/50 or better, and
      improvement of two or more lines were not statistically different between the two
      groups. CONCLUSION: ICG assisted ILM peeling in macular hole surgery for severely
      myopic eyes without retinal detachment gives promising anatomical and visual
      outcomes, which are comparable to that of non-severely myopic eyes.

PMID- 12812893
TI  - Digital analysis of choroidal neovascularisation in consecutive fluorescein
      angiograms for use in longitudinal clinical trials.
AB  - BACKGROUND/AIMS: To document the natural history and to assess the efficacy of
      interventional therapies in neovascular age related macular degeneration (AMD),
      an accurate and reproducible method is required for analysis of consecutive
      fluorescence angiograms. The development and evaluation of an image analysis
      software for this purpose is described here. It allows for the quantitative
      analysis of changes in CNV and/or leakage area over time. METHODS: In digitised
      angiograms, a mouse driven arrow was used to delineate the CNV border. The ratio
      of the CNV area to the square of the distance between two vessels was
      automatically calculated by pixel count to compensate for variation in image
      sizes at different examination times. These results were directly transferred and
      stored in a database. To assess reproducibility, CNV areas in 20 patients with
      occult and 20 patients with classic CNV were determined independently by two
      readers. RESULTS: There was only marginal variability between observers with this
      method: the mean deviation was 0.01 pixels for classic CNV (95% CI -0.17 to
      +0.15, SD 0.35) and 0.55 pixels for occult CNV (95% CI -1.06 to -0.04, SD 1.14).
      CONCLUSIONS: This practical PC based method allows for quantification of
      angiographic features such as CNV size in early frames and area of leakage in
      late frames. Limitations include non-readily defined borders in angiograms of
      poor image quality or indistinct borders of the hyperfluorescent areas of
      interest. The software is applicable to future clinical trials where the analysis
      of neovascular complex changes is required, for example, following therapeutic
      intervention.

PMID- 12812894
TI  - Genetic linkage analysis of a novel syndrome comprising North Carolina-like
      macular dystrophy and progressive sensorineural hearing loss.
AB  - AIM: To characterise the phenotype and identify the underlying genetic defect in
      a family with deafness segregating with a North Carolina-like macular dystrophy
      (NCMD). METHODS: Details of the family were obtained from the Moorfields Eye
      Hospital genetic clinic database and comprised eight affected, four unaffected
      members, and two spouses. Pedigree data were collated and leucocyte DNA extracted
      from venous blood. Positional candidate gene and genetic linkage strategies
      utilising polymerase chain reaction (PCR) based microsatellite marker genotyping
      were performed to identify the disease locus. RESULTS: The non-progressive ocular
      phenotype shared similarities with North Carolina macular dystrophy. Electro
      oculography and full field electroretinography were normal. Progressive
      sensorineural deafness was also present in all affected individuals over the age
      of 20 years. Hearing was normal in all unaffected relatives. Haplotype analysis
      indicated that this family is unrelated to previously reported families with
      NCMD. Genotyping excluded linkage to the MCDR1 locus and suggested a potential
      novel disease locus on chromosome 14q (Z=2.92 at theta=0 for marker D14S261).
      CONCLUSION: The combination of anomalies segregating in this family represents a
      novel phenotype. This molecular analysis indicates the disease is genetically
      distinct from NCMD.

PMID- 12812895
TI  - Retinal thickness decreases with age: an OCT study.
AB  - BACKGROUND/AIM: In three dimensional optic disc tomography a reference plane is
      required to calculate optic disc rim or cup values. The position of the reference
      plane often depends on the retinal thickness at the temporal disc margin.
      Originally it was assumed that the retinal thickness at the temporal disc margin
      is independent of age. The aim of the study was to check this hypothesis using
      optical coherence tomography, and additionally to determine the reproducibility
      of OCT measurements in this area. METHODS: 100 eyes of 100 healthy volunteers
      were included in this study. Three OCT scans were performed on each eye. The
      scans were aligned vertically and placed at the temporal edge of the optic disc.
      For each eye, the thickness of the whole retina as well as the thickness of the
      retinal nerve fibre layer were calculated together with their coefficients of
      variation. Thereafter retinal thickness and nerve fibre layer thickness were
      correlated with age. RESULTS: The mean retinal thickness was 249 (SD 22) micro m.
      The mean nerve fibre layer thickness was 109 (22) micro m. The mean coefficients
      of variation were 3.5% (total retinal thickness) and 8.0% (nerve fibre layer
      thickness). Both the total retinal thickness and the nerve fibre layer thickness
      were significantly correlated with age (total retina: y = 269.5 - 0.53 x x; R(2)
      = 0.133; p = 0.0002, nerve fibre layer: y = 126.8 - 0.44 x x; R(2) = 0.094;
      p<0.0019. CONCLUSIONS: Using OCT scans the total retinal thickness can be
      calculated with high reproducibility (coefficient of variation = 3.5%). The
      reproducibility of nerve fibre layer thickness measurements is clearly lower
      (coefficient of variation = 8.0%). Both the total retinal thickness and the nerve
      fibre layer thickness significantly decrease with age. This influence of the age
      related decrease in RNFL/retinal thickness on the reference plane, however, is
      negligible.

PMID- 12812896
TI  - Detecting chloroquine retinopathy: electro-oculogram versus colour vision.
AB  - AIM: To investigate the relative sensitivity and specificity of two tests of
      retinal function (the electro-oculogram (EOG) and a computerised colour vision
      test) in screening for ocular toxicity caused by chloroquine and
      hydroxychloroquine. METHODS: 93 patients with rheumatic diseases receiving long
      term chloroquine and hydroxychloroquine therapy were followed for an average of
      2.6 years. Clinical examination, an EOG, and a quantitative test of colour vision
      were carried out every 6 months. RESULTS: Mild fundus changes were observed in 38
      patients. Four patients developed typical bull's eye maculopathy, three of whom
      had received 250, 365, and 550 g total dose of chloroquine, and one 1500 g of
      hydroxychloroquine. Statistical analysis of all patients showed that for those
      with no fundus changes or stippled pigmentation a number showed elevation of
      tritan threshold, so that if macular stippling is a sign of mild retinopathy the
      test on tritan changes has a 64% sensitivity and 63% specificity for an upper
      threshold value of 7%. All four patients with bull's eye lesions showed a marked
      disturbance of tritan colour vision, with a threshold of 14.8%, a sensitivity of
      75%, and a specificity of 94%. For protan colour vision a threshold of 10% gives
      75% sensitivity and 91% specificity. By contrast, neither an absolute nor a
      relative EOG reduction was a valid criterion for early or late chloroquine
      retinopathy. In advanced retinopathy an Arden coefficient (AQ) <180% yields 50%
      sensitivity and 54% specificity. When AQ <160% is the threshold, sensitivity does
      not increase but specificity rises to 82%. Occurrence of marked corneal deposits
      on clinical examination yields 50% sensitivity and 90% specificity in this
      situation. CONCLUSION: Screening for chloroquine retinopathy can be improved by
      using a sensitive colour test. Disturbance of the tritan axis appears to occur
      first. A normal test result on computerised colour testing virtually excludes any
      retinopathy by antimalarials. The EOG is of little diagnostic value.

PMID- 12812897
TI  - Test characteristics of orthoptic screening examination in 3 year old
      kindergarten children.
AB  - AIM: To analyse the test characteristics of orthoptic screening for amblyopia or
      amblyogenic risk factors (target conditions) in kindergarten. METHODS: 1180 three
      year old children were screened by orthoptists in 121 German kindergartens.
      Orthoptic screening consisted of cover tests, examination of eye motility and
      head posture, and monocular visual acuity testing with the Lea single optotype
      test. Children were re-examined in kindergarten by different orthoptists after 3
      6 months using a more demanding pass threshold for visual acuity. All children
      with at least one positive orthoptic test result or an inconclusive re
      examination were referred to an ophthalmologist for diagnosis. The gold standard
      was set positive if a target condition was diagnosed on ophthalmological
      examination. It was set negative if no target condition was found upon
      ophthalmological examination, or if a child who screened negative or inconclusive
      passed the orthoptic re-examination without any positive test result. RESULTS:
      The gold standard was ascertained in 1114 children. 26 (2.3%) children had a
      "positive" gold standard. In 10.8% of the children the initial screening was
      "inconclusive," mostly due to lack of collaboration. Screening test sensitivity
      (based on conclusive results only) was 90.9% and specificity was 93.8%.
      CONCLUSIONS: Orthoptic vision screening of 3 year olds in kindergarten is
      sensitive and specific. However, owing to a substantial proportion of
      inconclusive screening results, rescreening of non-cooperative 3 year old
      children should be considered.

PMID- 12812898
TI  - Charles Bonnet syndrome precipitated by brimonidine tartrate eye drops.

PMID- 12812899
TI  - Botulinum toxin treatment of "one and a half syndrome".

PMID- 12812900
TI  - Trends in squint surgical activity.

PMID- 12812901
TI  - Retinal and subdural haemorrhages: Aoki revisited.

PMID- 12812902
TI  - Treatment of vascular tufts at the pupillary margin before cataract surgery.

PMID- 12812903
TI  - Treatment of retinal folds using a modified macula relocation technique with
      perfluoro-hexyloctane tamponade.

PMID- 12812904
TI  - Is hyaline degeneration of the cornea a precursor of Salzmann's corneal
      degeneration?

PMID- 12812905
TI  - Thyroid eye disease: an unusual presentation.

PMID- 12812906
TI  - Hospital acquired aspergillus keratitis.

PMID- 12812907
TI  - Mooren's ulcer resolved with campath-1H.

PMID- 12812908
TI  - Photodynamic therapy: a treatment option in choroidal neovascularisation
      secondary to punctate inner choroidopathy.

PMID- 12812909
TI  - Does etanercept induce uveitis?

PMID- 12812910
TI  - Non-invasive volumetric blood flow measurement in the orbit.

PMID- 12812911
TI  - "Compliance" with treatment in amblyopia is an important factor affecting the
      final visual outcome.

PMID- 12812912
TI  - Can a cilio-retinal artery influence diabetic retinopathy?

PMID- 12812914
TI  - An increase in intracellular calcium concentration that is induced by basolateral
      CO2 in rabbit renal proximal tubule.
AB  - Working with isolated perfused S2 proximal tubules, we asked whether the
      basolateral CO2 sensor acts, in part, by raising intracellular Ca2+ concentration
      ([Ca2+]i), monitored with the dye fura 2 (or fura-PE3). In paired experiments,
      adding 5% CO2/22 mM HCO3- (constant pH 7.40) to the bath (basolateral) solution
      caused [Ca2+]i to increase from 57 +/- 3 to 97 +/- 9 nM(n = 8, P < 0.002),
      whereas the same maneuver in the lumen had no effect. Intracellular pH (pHi),
      measured with the dye BCECF, fell by 0.54 +/- 0.08 (n = 14) when we added
      CO2/HCO3- to the lumen. In 14 tubules in which we added CO2/HCO3- to the bath,
      pHi fell by 0.55 +/- 0.11 in 9 with a high initial pHi, but rose by 0.28 +/- 0.07
      in the other 5 with a low initial pHi. Thus it cannot be a pHi change that
      triggers the [Ca2+]i increase. Introducing to the bath an out-of-equilibrium
      (OOE) solution containing 20% CO2/no HCO3-/pH 7.40 caused [Ca2+]i to rise by 62
      +/- 17 nM (n = 10), whereas an OOE solution containing 0% CO2/22 mM HCO3-/pH 7.40
      caused only a trivial increase. Removing Ca2+ from the lumen and bath, or adding
      10 microM nifedipine (L- and T-type Ca2+-channel blocker) or 2 microM
      thapsigargin [sarco-(endo) plasmic reticulum Ca2+-ATPase inhibitor] or 4 microM
      rotenone (mitochondrial inhibitor) to the lumen and bath, failed to reduce the
      CO2-induced increase in [Ca2+]i. Adding 10 mM caffeine (ryanodine-receptor
      agonist) had no effect on [Ca2+]i. Thus basolateral CO2, presumably via a
      basolateral sensor, triggers the release of Ca2+ from a nonconventional
      intracellular pool.

PMID- 12812915
TI  - Role of oxidative stress and heme oxygenase activity in morphine-induced
      glomerular epithelial cell growth.
AB  - Opiate addiction has been reported to contribute to the progression of renal
      injury. In addition, opiate addiction is a major risk factor for the development
      of human immunodeficiency virus-associated nephropathy. In the present study, we
      evaluated the effects of morphine, an active metabolite of heroin, on glomerular
      epithelial cell (GEC) growth and the involved molecular mechanism. At lower
      concentrations, morphine promoted GEC proliferation; however, at higher
      concentrations, morphine triggered apoptosis. Antioxidants inhibited morphine
      induced proliferation as well as apoptosis. Similarly, free radical scavengers
      prevented morphine-induced GEC proliferation and apoptosis. Because proliferative
      and proapoptotic effects of morphine were inhibited by free radical scavengers as
      well as antioxidants, it appears that these effects of morphine are mediated
      through oxidative stress. Hemin, an inducer of heme oxygenase (HO) activity,
      inhibited GEC proliferation and promoted GEC apoptosis under basal and morphine
      stimulated conditions. On the other hand, zinc protoporphyrin, an inhibitor of HO
      activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as
      well as morphine-stimulated conditions. These findings suggest that HO activity
      is directly related to GEC apoptosis and inversely related to GEC proliferation.
      Morphine, de novo, had bimodal effects on HO activity: lower concentrations
      increased and higher concentrations decreased HO activity. It appears that HO
      activity may be modifying morphine-induced GEC growth.

PMID- 12812916
TI  - Rat kidney MAP17 induces cotransport of Na-mannose and Na-glucose in Xenopus
      laevis oocytes.
AB  - Renal reabsorption is the main mechanism that controls mannose homeostasis. This
      takes place through a specific Na-coupled uphill transport system, the molecular
      identity of which is unknown. We prepared and screened a size-selected rat kidney
      cortex cDNA library through the expression of mannose transport in Xenopus laevis
      oocytes. We have identified a membrane protein that induces high-affinity and
      specific Na-dependent transport of d-mannose and d-glucose in X. laevis oocytes,
      most likely through stimulation of the capacity of an endogenous transport system
      of the oocyte. Sequencing has revealed that the cDNA encodes the counterpart of
      the human membrane-associated protein MAP17, previously known by its
      overexpression in renal, colon, lung, and breast carcinomas. We show that MAP17
      is a 12.2-kDa nonglycosylated membrane protein that locates to the brush-border
      plasma membrane and the Golgi apparatus of transfected cells and that it is
      expressed in the proximal tubules of the kidney cortex and in the spermatids of
      the seminiferous tubules. It spans twice the cell membrane, with both termini
      inside the cell, and seems to form homodimers through intracellular Cys55, a
      residue also involved in transport expression. MAP17 is responsible for mannose
      transport expression in oocytes by rat kidney cortex mRNA. The induced transport
      has the functional characteristics of a Na-glucose cotransporter (SGLT), because
      d-glucose and alpha-methyl-d-glucopyranoside are also accepted substrates that
      are inhibited by phloridzin. The corresponding transporter from the proximal
      tubule remains to be identified, but it is different from the known mammalian
      SGLT-1, -2, and -3.

PMID- 12812917
TI  - Dynamic alterations of glomerular charge density in fixed rat kidneys suggest
      involvement of endothelial cell coat.
AB  - In a previous paper, we found that low ionic strength (I) reversibly reduced the
      glomerular charge density, suggesting increased volume of the charge-selective
      barrier. Because glutaraldehyde makes most structures rigid, we considered the
      isolated, perfusion-fixed rat kidney to be an ideal model for further analysis.
      The fixed kidneys were perfused with albumin solutions containing FITC-Ficoll at
      two different Is (I = 151 and 34 mM). At normal I, the fractional clearance ()
      for albumin was 0.0049 (SE -0.0017, +0.0027, n = 6), whereas for neutral
      Ficoll35.5A of similar size was significantly higher 0.104 (SE 0.010, n = 5, P <
      0.001). At low I, for albumin was 0.0030 (SE -0.0011, +0.0018, n = 6, not
      significant from albumin at normal I) and for Ficoll35.5A was identical to that
      at normal I, 0.104 (SE 0.015, n = 6, P < 0.01 compared with albumin at low I).
      According to a heterogeneous charged fiber model, low I reduced the fiber density
      from 0.056 to 0.0315, suggesting a 78% gel volume expansion. We conclude that 1)
      there is a significant glomerular charge barrier. 2) Solutions with low I
      increase the volume of the charge barrier even in kidneys fixed with
      glutaraldehyde. Our findings suggest that polysaccharide-rich structures, such as
      the endothelial cell coat, are key components in the glomerular barrier.

PMID- 12812918
TI  - Potential role of leucine metabolism in the leucine-signaling pathway involving
      mTOR.
AB  - Leucine has been shown to stimulate adipose tissue protein synthesis in vivo as
      well as leptin secretion, protein synthesis, hyper-plastic growth, and tissue
      morphogenesis in in vitro experiments using freshly isolated adipocytes.
      Recently, others have proposed that leucine oxidation in the mitochondria may be
      required to activate the mammalian target of rapamycin (mTOR), the cytosolic
      Ser/Thr protein kinase that appears to mediate some of these effects. The first
      irreversible and rate-limiting step in leucine oxidation is catalyzed by the
      branched-chain alpha-keto acid dehydrogenase (BCKD) complex. The activity of this
      complex is regulated acutely by phosphorylation of the E1alpha-subunit at Ser293
      (S293), which inactivates the complex. Because the alpha-keto acid of leucine
      regulates the activity of BCKD kinase, it has been suggested as a potential
      target for leucine regulation of mTOR. To study the regulation of BCKD
      phosphorylation and its potential link to mTOR activation, a phosphopeptide
      specific antibody recognizing this site was developed and characterized. Phospho
      S293 (pS293) immunoreactivity in liver corresponded closely to diet-induced
      changes in BCKD activity state. Immunoreactivity was also increased in TREMK-4
      cells after the induction of BCKD kinase by a drug-inducible promoter. BCKD S293
      phosphorylations in adipose tissue and gastrocnemius (which is mostly inactive in
      vivo) were similar. This suggests that BCKD complex in epididymal adipose tissue
      from food-deprived rats is mostly inactive (unable to oxidize leucine), as is the
      case in muscle. To begin to test the leucine oxidation hypothesis of mTOR
      activation, the dose-dependent effects of orally administered leucine on acute
      activation of S6K1 (an mTOR substrate) and BCKD were compared using the pS293
      antibodies. Increasing doses of leucine directly correlated with increases in
      plasma leucine concentration. Phosphorylation of S6K1 (Thr389, the
      phosphorylation site leading to activation) in adipose tissue was maximal at a
      dose of leucine that increased plasma leucine approximately threefold. Changes in
      BCKD phosphorylation state required higher plasma leucine concentrations. The
      results seem more consistent with a role for BCKD and BCKD kinase in the
      activation of leucine metabolism/oxidation than in the activation of the leucine
      signal to mTOR.

PMID- 12812919
TI  - Gene expression profiles and protein balance in skeletal muscle of burned
      children after beta-adrenergic blockade.
AB  - Propranolol, a nonselective beta-blocker, has been shown effective in
      hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and
      lipolysis. This study investigates the effect of propranolol on gene and protein
      expression changes in skeletal muscle of burned children by use of high-density
      oligonucleotide arrays to establish the genetic profiles and stable isotope
      technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 +/
      1.1 yr) were randomized into groups to receive placebo (n = 23) or propranolol
      (n = 14) titrated to reduce heart rate by 15%. Children had >40% total body
      surface area burns (mean 43 +/- 5.6%). Protein net balance was determined by
      stable-isotope infusion technique. Total RNA from muscle biopsies was isolated,
      labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance
      of protein synthesis and breakdown was -14.3 +/- 12.9 nmol. min-1. 100 ml leg
      volume-1 for placebo and +69.3 +/- 34.9 nmol. min-1. 100 ml leg volume-1 in the
      propranolol-treated children (P = 0.012). Comparison of 12,000 genes in burned
      children receiving placebo showed increased expression of two genes with time,
      whereas children receiving propranolol showed increased expression of nine genes
      with a decrease in five genes. We conclude that burned children receiving
      propranolol showed a significant upregulation in genes involved in muscle
      metabolism and downregulation of an important enzyme involved in gluconeogenesis
      and insulin resistance compared with burned children receiving placebo. The
      upregulation of genes involved in muscle metabolism correlates well with the
      increase in net protein balance across the leg.

PMID- 12812920
TI  - Zinc modulates mRNA levels of cytokines.
AB  - Zinc plays an important role in cell-mediated immune function. Altered cellular
      immune response resulting from zinc deficiency leads to frequent microbial
      infections, thymic atrophy, decreased natural killer activity, decreased thymic
      hormone activity, and altered cytokine production. In this study, we examined the
      effect of zinc deficiency on IL-2 and IFN-gamma in HUT-78 (Th0) and D1.1 (Th1)
      cell lines and TNF-alpha, IL-1 beta, and IL-8 in the HL-60 (monocyte-macrophage)
      cell line. The results demonstrate that zinc deficiency decreased the levels of
      IL-2 and IFN-gamma cytokines and mRNAs in HUT-78 after 6 h of PMA/p
      phytohemagglutinin (PHA) stimulation and in D1.1 cells after 6 h of PHA/ionomycin
      stimulation compared with the zinc-sufficient cells. However, zinc deficiency
      increased the levels of TNF-alpha, IL-1 beta, and IL-8 cytokines and mRNAs in HL
      60 cells after 6 h of PMA stimulation compared with zinc-sufficient cells.
      Actinomycin D study suggests that the changes in the levels of these cytokine
      mRNAs were not the result of the stability affected by zinc but might be the
      result of altered expression of these cytokine genes. These data demonstrate that
      zinc mediates positively the gene expression of IL-2 and IFN-gamma in the Th1
      cell line and negatively TNF-alpha, IL-1 beta, and IL-8 in the monocyte
      macrophage cell line. Our study shows that the effect of zinc on gene expression
      and production of cytokines is cell lineage specific.

PMID- 12812921
TI  - Unlocking the mental aspects of the golf swing: can functional MR imaging give us
      insights?

PMID- 12812922
TI  - Preoperative evaluation of carotid artery stenosis: comparison of contrast
      enhanced MR angiography and duplex ultrasonography with digital subtraction
      angiography.

PMID- 12812924
TI  - The mind's eye: functional MR imaging evaluation of golf motor imagery.
AB  - BACKGROUND AND PURPOSE: Mental imagery involves rehearsing or practicing a task
      in the mind with no physical movement. The technique is commonly used, but the
      actual physical foundation of imagery has not been evaluated for the fast,
      complex, automatic motor movement of the golf swing. This study evaluated motor
      imagery of the golf swing, of golfers of various handicaps, by using functional
      MR imaging to assess whether areas of brain activation could be defined by this
      technique and to define any association between activated brain areas and golf
      skill. METHODS: Six golfers of various handicap levels were evaluated with
      functional MR imaging during a control condition and during mental imagery of
      their golf swing. Two control conditions were evaluated--"rest" and "wall"--and
      were then subtracted from the experimental condition to give the functional
      activation map. These control conditions were then tested against the golf
      imagery; the participants were told to mentally rehearse their golf swings from a
      first person perspective. The percentages of activated pixels in 137 defined
      regions of interest were calculated. RESULTS: The "rest-versus-golf" paradigm
      showed activation in motor cortex, parietal cortex, frontal lobe, cerebellum,
      vermis, and action planning areas (frontal and parietal cortices, supplementary
      motor area, cerebellum) and areas involved with error detection (cerebellum).
      Vermis, supplementary motor area, cerebellum, and motor regions generally showed
      the greatest activation. Little activation was seen in the cingulate gyrus, right
      temporal lobe, deep gray matter, and brain stem. A correlation existed between
      increased number of areas of activation and increased handicap. CONCLUSION: This
      study showed the feasibility of defining areas of brain activation during imagery
      of a complex, coordinated motor task. Decreased brain activation occurred with
      increased golf skill level for the supplementary motor area and cerebellum with
      little activation of basal ganglia.

PMID- 12812925
TI  - Curved-surface projection: an alternative method for visualizing functional MR
      imaging results.
AB  - Curved-surface projection (CSP) is a new technique for visualizing functional MR
      imaging data. This technique helps in identifying anatomic structures by
      demonstrating the whole gyral and sulcal pattern of the brain at once. Compared
      with other techniques, CSP preserves the spatial relation of eloquent areas to
      lesions. Especially in neurosurgical patients with space-occupying lesions, CSP
      helps in assigning the anatomy to its function.

PMID- 12812926
TI  - Diffuse axonal injury associated with chronic traumatic brain injury: evidence
      from T2*-weighted gradient-echo imaging at 3 T.
AB  - BACKGROUND AND PURPOSE: Diffuse axonal injury is frequently accompanied by tissue
      tear hemorrhages. We examined whether high field strength T2*-weighted gradient
      echo imaging performed during the chronic stage of traumatic brain injury may
      have advantages in the evaluation of diffuse axonal injury as compared with T1-
      and T2-weighted MR imaging. METHODS: Prospective MR imaging of 66 patients (age
      range, 17-57 years) was performed using a 3-T system 3 to 292 months (median,
      23.5 months) after traumatic brain injury. T1-, T2-, T2*-hypointense and T2
      hyperintense foci of 1- to 15-mm diameter were registered in 10 brain regions by
      two readers separately. Foci that appeared hypointense both on the T1- and T2-
      and/or on the T2*-weighted images were defined as traumatic microbleeds. RESULTS:
      For 46 (69.7%) of the patients, T2*-weighted gradient-echo imaging revealed
      traumatic microbleeds. Hyperintense foci were observed on the T2-weighted images
      of only 15 (22.7%) patients. T2*-weighted imaging showed significantly more
      traumatic microbleeds (P =.000) than did T1- and T2-weighted imaging.
      Interobserver agreement was strong (kappa = 0.79, tau = 0.749, P =.000). For 14
      (21.2%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic
      microbleeds in the corpus callosum, whereas for only two (3%), hyperintense
      callosal lesions were seen on the T2-weighted images. Although a significant
      correlation existed between the total amount and callosal appearance of traumatic
      microbleeds and Glasgow Coma Scale scores (P =.000), no correlation existed with
      extended Glasgow Outcome Scale scores. CONCLUSION: T2*-weighted gradient-echo
      imaging at high field strength is a useful tool for the evaluation of diffuse
      axonal injury during the chronic stage of traumatic brain injury. Diffuse axonal
      injury-related brain lesions are mainly hemorrhagic. The relevance of diffuse
      axonal injury for long-term clinical outcome is uncertain.

PMID- 12812927
TI  - Diffusion-weighted imaging of acute corticospinal tract injury preceding
      Wallerian degeneration in the maturing human brain.
AB  - BACKGROUND AND PURPOSE: Wallerian degeneration, the secondary degeneration of
      axons from cortical and subcortical injury, is associated with poor neurologic
      outcome. Since diffusion-weighted (DW) imaging is sensitive to early changes of
      cytotoxic edema, DW imaging may depict the acute injury to descending white
      matter tracts that precedes Wallerian degeneration; this injury is not visible on
      conventional CT or MR images in the maturing human brain. METHODS: Two
      neuroradiologists retrospectively analyzed clinical MR images in six children
      (aged 3 days to 5 months) with DW findings consistent with acute injury of the
      descending white matter tract due to territorial anterior or middle cerebral
      artery infarction. In five patients, images were obtained as a part of routine
      clinical evaluation. The remaining patient was a part of a prospective study of
      brain injury. Imaging findings were correlated with clinical outcomes. RESULTS:
      In all six patients, DW imaging performed 2-8 days after the onset of ischemia
      depicted injury to the descending white matter tract ipsilateral to the
      territorial infarct. Conventional MR images of the ipsilateral descending white
      matter tracts were abnormal in three patients. In all five patients for which
      follow-up results were available, the presence of DW changes was correlated with
      persistent neurologic disability. CONCLUSION: As shown in this retrospective
      analysis, DW imaging can depict acute injury to the descending white matter tract
      in neonates and infants, when conventional MR imaging may show normal findings.
      These DW findings likely precede the development of Wallerian degeneration, and
      they may portend a poor clinical outcome.

PMID- 12812928
TI  - Clinical usefulness of unsubtracted 3D digital angiography compared with
      rotational digital angiography in the pretreatment evaluation of intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: Three-dimensional digital subtraction angiography (DSA)
      is useful as a supplement to 2D DSA in the pretreatment evaluation of
      intracranial aneurysms. However, the clinical efficacy of 3D digital angiography
      (DA) that is generated from unsubtracted rotational images has not been
      established. The purpose of this study was to assess whether 3D DA provides
      additional useful information to that of rotational DA in the preoperative
      evaluation of intracranial aneurysms. METHODS: This prospective study comprised
      23 patients (age range, 37-83 years) with ruptured aneurysms who underwent
      angiography. Two radiologists independently evaluated the rotational DA images
      and the maximum intensity projection, shaded surface display, and volume
      rendering 3D DA images, in combination with 2D DSA images. A four-point scoring
      system was used to evaluate aneurysm detection and delineation. Referring
      neurosurgeons were questioned as to whether the information obtained with 3D DA
      was useful for treatment decisions. RESULTS: Thirty aneurysms were confirmed by
      surgery or endovascular treatment. In detection and delineation of the 30
      confirmed aneurysms, overall mean scores were highest with volume-rendering 3D DA
      and lowest with rotational DA. Compared with rotational DA, volume-rendering 3D
      DA demonstrated 27 additional findings in 14 (47%) of 30 aneurysms: detection of
      an aneurysm (n = 2), and delineation of aneurysm neck, shape, and relationship to
      adjacent arteries (n = 25). The information provided by 3D DA was useful for
      following treatment in five (22%) of 23 patients. CONCLUSION: In the preoperative
      evaluation of intracranial aneurysms, 3D DA can provide additional useful
      information to that of rotational DA.

PMID- 12812929
TI  - Hemodynamic analysis of an adult vein of Galen aneurysm malformation by use of 3D
      image-based computational fluid dynamics.
AB  - We applied computational fluid dynamic (CFD) analysis on the numerical grid of a
      3D rotational digital subtraction angiogram obtained in a 22-year-old male
      patient, with an accidentally discovered vein of Galen malformation associated
      with single feeder aneurysm, to understand the flow pattern through the two
      aneurysms and improve our general understanding of hemodynamic characteristics of
      this variety of fusiform aneurysm. This technical note provides a good example of
      the application of CFD to 3D digital subtraction angiography for studying the
      flow pattern in patients with cerebrovascular disease.

PMID- 12812930
TI  - Role of subvoxel free fluid on diffusion parameters in brain tissue with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      and its correlation with physical disability: histogram analysis of standard and
      fluid-attenuated MR diffusion.
AB  - BACKGROUND AND PURPOSE: Subcortical signal intensity abnormalities and lacunar
      infarcts are the radiologic hallmark of cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy. MR diffusion studies reveal
      abnormalities in lesions and also within normal appearing white matter. To
      further characterize the underlying pathologic abnormality, we evaluated the role
      of subvoxel free fluid in brain with cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy on diffusion parameters and
      physical disability and analyzed the interrelation between diffusion variables
      and nonlacunar T2 lesion load. METHODS: Mean diffusivity maps from fluid
      attenuated and standard diffusion images of 13 patients with cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy and seven
      age-matched control participants were compared by means of histogram analysis for
      three tissue compartments (whole brain parenchyma, normal appearing brain tissue,
      and nonlacunar lesions) by using a semiautomated region growing algorithm to
      define whole brain parenchyma and lesions on fluid-attenuated images. RESULTS: In
      both patients and control participants, the average mean diffusivity of whole
      brain parenchyma was lower on fluid-attenuated than on standard images (P <.001).
      Average mean diffusivity and peak location for all compartments were
      significantly elevated in patients (P <.001) and higher for lesions than for
      normal appearing brain tissue on both types of images (P <.001). The difference
      between standard and fluid-attenuated average mean diffusivity of normal
      appearing brain tissue, reflecting the subvoxel free fluid content, was elevated
      in patients (P <.05) and correlated closely with the Rankin score (Spearman's
      rank correlation coefficient = 0.889, P <.001). Average mean diffusivity of whole
      brain parenchyma and normal appearing brain tissue correlated strongly with the
      nonlacunar T2 lesion load (Pearson's correlation coefficient = 0.743-0.928, P
      <.005). CONCLUSION: This study shows that standard diffusion measurements are
      contaminated by free fluid partial volume effects for patients with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      and for control participants. It also provides evidence of a clinical
      significance of increased subvoxel free fluid in normal appearing brain with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, which may be more important than either global atrophy,
      increased diffusivity or, T2 lesion load.

PMID- 12812931
TI  - Qualitative versus quantitative assessment of cerebrovascular reactivity to
      acetazolamide using iodine-123-N-isopropyl-p-iodoamphetamine SPECT in patients
      with unilateral major cerebral artery occlusive disease.
AB  - BACKGROUND AND PURPOSE: Qualitative measurement of regional cerebrovascular
      reactivity (rCVR) to acetazolamide with single-photon emission CT (SPECT) has
      been widely used to determine the severity of hemodynamic impairment. We
      attempted to validate the accuracy of qualitative assessment by using SPECT to
      detect reduced rCVR compared with rCVR determined quantitatively in patients with
      unilateral major cerebral artery occlusion. METHODS: Regional cerebral blood flow
      was assessed with iodine-123-N-isopropyl-p-iodoamphetamine ((123)I-IMP) at rest
      and after acetazolamide activation in 133 patients with previously symptomatic,
      unilateral internal carotid or middle cerebral artery occlusion. Quantitative
      values were calculated by using the (123)I-IMP autoradiographic method and
      analyzed for each cerebral hemisphere as the percentage change in rCBF between
      resting and activation studies (%(Hem)). Qualitative rCVR was determined for the
      target hemisphere distal to the occlusion as the cerebral-interhemispheric
      asymmetry index (AI(Hem)) and as an index of flow difference between the target
      cerebral and ipsilateral cerebellar hemispheres (FI(Hem-Cbl)). Values 2 SDs below
      the mean in healthy volunteers were defined as decreased. RESULTS: Fair agreement
      was observed between %(Hem) and both AI(Hem) change (resting vs activation, kappa
      = 0.409) and FI(Hem-Cbl) change (resting vs activation, kappa = 0.440). When
      %(Hem) was assumed to represent the true determinant of assessing rCVR, AI(Hem)
      change and FI(Hem-Cbl) change demonstrated sensitivities of 68% and 78%;
      specificities, 72% and 76%; positive predictive values, 48% and 56%; false
      positive incidences, 28% and 24%; and false-negative incidences, 32% and 22% for
      detecting patients with reduced rCVR, respectively. CONCLUSION: Subgroups of
      patients with hemodynamic impairment cannot be accurately defined by using rCVR
      qualitatively measured with SPECT.

PMID- 12812932
TI  - Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic
      MR imaging sign of Fabry disease.
AB  - BACKGROUND AND PURPOSE: Fabry disease is a multisystem X-linked disorder
      characterized clinically by angiokeratoma, corneal and lenticular abnormalities,
      acroparesthesia, and renal and cardiac dysfunction and stroke. We sought to
      describe novel neuroimaging characteristics of Fabry disease. METHODS:
      Neuroradiologic records of 104 hemizygous patients with Fabry disease evaluated
      between 1994 and 2002 were reviewed. In total, 94 MR studies consisting of T1-
      and T2-weighted images were examined for the presence of hyperintensity on the T1
      weighted images. Additional CT, gradient-echo (T2*-weighted), and fat-suppression
      MR studies were reviewed to characterize further the T1 abnormality in selected
      patients. In some patients, cerebral blood flow (CBF) was quantified by using
      arterial spin tagging (AST). RESULTS: Overall, 22 patients ( approximately 23%)
      demonstrated pulvinar hyperintensity on T1-weighted images; the frequency
      increased with age to over 30% by age 50 years. Susceptibility-weighted T2*
      studies demonstrated a low-signal-intensity abnormality in the pulvinar in the
      more severe cases, whereas CT demonstrated the pulvinar to be mineralized. CT
      attenuation corresponded with an increasing signal intensity on T1-weighted
      images. Posterior circulation CBF was found to be elevated on individual AST
      studies, especially in the thalamus. CONCLUSION: Hyperintensity in the pulvinar
      on T1-weighted images is a common finding in Fabry disease, likely reflecting the
      presence of calcification. Although other minreralizing abnormalities may result
      in calcification of deep gray nuclei, exclusive involvement of the pulvinar may
      be distinctively characteristic to Fabry disease. Increased CBF in the posterior
      circulation, particularly the thalamus, suggests that the dystrophic
      calcification is secondary to cerebral hyperperfusion and selective vulnerability
      of the pulvinar and adjacent thalamic nuclei. The finding of isolated pulvinar
      hyperintensity on T1-weighted images should suggest Fabry disease, particularly
      when seen in conjunction with other nonspecific neuroradiologic manifestations of
      the disease.

PMID- 12812933
TI  - MR imaging in human rabies.
AB  - BACKGROUND AND PURPOSE: Whether human rabies of different forms, encephalitic
      (furious) and paralytic (dumb), share similar MR imaging patterns is unknown. We
      assessed the diagnostic value of MR imaging in both forms of the disease and
      compared the clinical and neuroimaging findings. METHODS: Three patients with
      paralytic and two with encephalitic rabies were examined during preserved or
      deteriorated levels of consciousness. Six MR examinations of the brain, three of
      the spinal cord, and one of the brachial plexus were performed with a 1.5-T
      superconducting magnet. RESULTS: No difference was noted between the MR findings
      in both clinical forms of human rabies. Nonenhancing, ill-defined, mild
      hyperintensity changes in the brain stem, hippocampi, hypothalami, deep and
      subcortical white matter, and deep and cortical gray matter were demonstrated on
      T2-weighted images in the noncomatose patients with rabies. Enhancement along the
      brachial plexus of the bitten arm was noted in one patient with encephalitic
      rabies who at that time had only local neuropathic pain symptoms. Enhancement
      with gadolinium-based contrast material was seen at the hypothalami, brain stem
      nuclei, spinal cord gray matter, and intradural cervical nerve roots only when
      the patients became comatose. CONCLUSION: Both forms of human rabies share a
      similar MR imaging pattern. Such pattern and the lack of enhancement in a
      noncomatose patient with suspected encephalitis may differentiate rabies from
      other viral encephalitides.

PMID- 12812934
TI  - Diffusion-weighted imaging of cerebritis.
AB  - Restricted water diffusion has been used to distinguish pyogenic abscess from
      other rim-enhancing brain masses; however diffusion-weighted imaging of cerebral
      infection before capsule formation has rarely been described. We report a case of
      fungal cerebritis in which water diffusion was more restricted than that of
      normal contralateral brain and the measured diffusion coefficient was in the
      range of that reported for pyogenic brain abscess. In the proper clinical
      setting, cerebritis should be considered in the differential diagnosis of an ill
      defined focal brain mass associated with markedly restricted water diffusion.

PMID- 12812935
TI  - Cortical blindness after contrast-enhanced CT: complication in a patient with
      diabetes insipidus.
AB  - Transient cortical blindness is an uncommon but well-known complication following
      cerebral angiography. One possible cause of this complication is an adverse
      reaction to contrast agent, resulting in an osmotic disruption of the blood-brain
      barrier that seems to be selective for the occipital cortex. We report the case
      of a 16-year-old male patient with cortical blindness after intravenous
      application of nonionic contrast agent during CT angiography performed because of
      seizure that was attributed to thrombosis of the basilar artery on the basis of
      clinical findings. To our knowledge, the development of cortical blindness after
      CT angiography has not been described in the literature. The patient's symptoms
      were triggered by hyponatriemia and diabetes insipidus.

PMID- 12812936
TI  - Preoperative evaluation of carotid artery stenosis: comparison of contrast
      enhanced MR angiography and duplex sonography with digital subtraction
      angiography.
AB  - BACKGROUND AND PURPOSE: Contrast-enhanced MR angiography and extracranial color
      coded duplex sonography are noninvasive, preoperative imaging modalities for
      evaluation of carotid artery stenosis. Innovative techniques and improvements in
      image quality require frequent reassessment of accuracy, reliability, and
      diagnostic value compared with those of digital subtraction angiography (DSA). We
      evaluated contrast-enhanced MR angiography and duplex sonography compared with
      DSA for detection of high-grade carotid artery stenoses. METHODS: Four readers,
      blinded to clinical symptoms and the outcome of other studies, independently
      evaluated stenoses on contrast-enhanced MR angiograms in 71 vessels of 39
      symptomatic patients. Duplex sonography was also performed in all vessels. The
      severity of stenosis was defined according to North American Symptomatic Carotid
      Endarterectomy Trial criteria (0-29%, 30-69%, 70-99%, 100%). Results of both
      modalities were compared with the corresponding DSA findings. RESULTS: Contrast
      enhanced MR angiography had a sensitivity and specificity of 94.9% and 79.1%,
      respectively, for the identification of carotid artery stenoses of 70% or
      greater. Sensitivity and specificity of duplex sonography were 92.9% and 81.9%,
      respectively. Combining data from both tests revealed a sensitivity and
      specificity of 100% and 81.4%, respectively, for concordant results (80% of
      vessels). CONCLUSION: Concordant results of contrast-enhanced MR angiography and
      duplex sonography increase the diagnostic sensitivity to 100%. The reliability of
      MR angiography is comparable to that of DSA. The combination of contrast-enhanced
      MR angiography and duplex sonography might be preferable over DSA for
      preoperative evaluation in most patients, thus reducing the risk of perioperative
      morbidity and improving the overall outcome.

PMID- 12812937
TI  - Total occlusion versus hairline residual lumen of the internal carotid arteries:
      accuracy of single section helical CT angiography.
AB  - BACKGROUND AND PURPOSE: Routine carotid sonography and MR angiography cannot
      reliably detect the markedly reduced flow velocities associated with very severe
      carotid stenosis. In this study, we sought to evaluate the accuracy of single row
      detector helical CT angiography in distinguishing hairline residual lumen from
      total occlusion of severely stenosed internal carotid arteries (ICAs). METHODS:
      From our departmental data base of single row detector CT angiography studies
      performed for evaluation of ICA occlusive disease, 21 cases were identified with
      evidence of either hairline residual lumen or total occlusion on correlative
      conventional catheter radiographic arteriograms; these included seven cases of
      proved hairline residual lumen and 14 cases of proved total occlusion. Two
      neuroradiologists, blinded to the radiographic arteriography results, graded the
      diseased ICA on each CT angiogram as definitely occluded, probably occluded,
      indeterminate, probably patent, or definitely patent. Receiver operating
      characteristic curves were generated for each neuroradiologist. RESULTS: At an
      operating point on the receiver operating characteristic curve corresponding to
      90% sensitivity, the first reader achieved 95% specificity and the second reader
      achieved 80% specificity for distinguishing hairline residual lumen from total
      occlusion. Absolute accuracy rates were 95% and 85%, respectively. No significant
      difference in accuracy was observed between the two readers (P =.28, two-tailed t
      test). CONCLUSION: Single row detector CT angiography can distinguish total ICA
      occlusion from hairline residual lumen with a high degree of accuracy. In
      equivocal cases, conventional catheter arteriography may be desirable to confirm
      the diagnosis.

PMID- 12812938
TI  - X-linked stapes gusher: CT findings in one patient.
AB  - A 31-year-old male patient presented with progressive mixed hearing loss since
      birth. A stapedectomy was attempted and was unsuccessful because of perilymph
      gushing. CT of the temporal bones showed bulbous dilatation of the fundi of the
      internal auditory canals and absence of the bone plates separating them from the
      base of the cochleas. This unusual abnormality was found after the attempted
      stapedectomy and explains the clinical findings. The findings in male patients
      are fairly typical X-linked congenital deafness.

PMID- 12812939
TI  - Persistent stapedial artery: MR angiographic and CT findings.
AB  - A 2-year-old girl was found to have a pink pulsatile mass behind the right
      tympanic membrane on physical examination. We report the high-resolution CT and
      MR angiographic findings of persistent stapedial artery with hypoplasia of the A1
      segment of the right anterior cerebral artery.

PMID- 12812940
TI  - Giant cell reparative granuloma of the temporal bone: MR findings with pathologic
      correlation.
AB  - We report MR findings in a case of a giant cell reparative granuloma involving
      the temporal lobe in a middle-aged man. On MR images, most of the mass was
      hypointense on T1-weighted images, hypointense on T2-weighted images, and mildly
      enhanced on postcontrast T1-weighted images. The hypointensity on T2-weighted
      images corresponded to areas of hemorrhage and hemosiderin deposition on
      pathologic correlation.

PMID- 12812941
TI  - Bilateral petrous internal carotid artery pseudoaneurysms presenting with
      sensorineural hearing loss.
AB  - We present a case of an 85-year-old woman with a 40-year history of progressive
      bilateral sensorineural hearing loss. Imaging studies demonstrated bilateral
      pseudoaneurysms of the petrous portion of the internal carotid arteries eroding
      into both cochleas. To our knowledge, this is the first case report of such
      lesions.

PMID- 12812942
TI  - The skull and cervical spine radiographs of Tutankhamen: a critical appraisal.
AB  - BACKGROUND AND PURPOSE: Tutankhamen, the last pharaoh of the XVIIIth dynasty,
      died unexpectedly at approximately age 18 years. A cause of death has never been
      established, but theories that the young king was murdered by a blow to the head
      have been proposed based on skull radiographs obtained by a team from the
      University of Liverpool in 1968. We recently had the opportunity to evaluate the
      skull and cervical spine radiographs of Tutankhamen. The purpose of this study
      was to report our critical appraisal of the radiographs of Tutankhamen regarding
      the findings alleged to indicate traumatic death. METHODS: Copies of lateral,
      anteroposterior, and submental vertex skull radiographs of Tutankhamen were
      reviewed with special attention to the claims of a depressed skull fracture,
      intracranial bone fragments, and calcified membrane of a posterior fossa subdural
      hematoma. A phantom skull was radiographed to reproduce the appearance of the
      floor of the posterior fossa in the lateral projection. RESULTS: The skull
      radiographs of Tutankhamen show only postmortem artifacts that are explainable by
      an understanding of the methods of mummy preservation used at the time of his
      death. Some findings also relate to trauma inflicted by an autopsy performed in
      1925. The alleged calcified membrane of a posterior fossa subdural hematoma is
      easily reproduced with a skull phantom. CONCLUSION: Our critical review of the
      skull and cervical spine radiographs of Tutankhamen does not support proposed
      theories of a traumatic or homicidal death.

PMID- 12812943
TI  - Characteristic MR imaging findings of cavernous hemangiomas in the cavernous
      sinus.
AB  - Cavernous hemangiomas occur very rarely in the cavernous sinus and are difficult
      to diagnose preoperatively. MR images obtained in five patients with surgically
      verified cavernous hemangiomas in the cavernous sinus were reviewed. MR images
      showed hypointensity on T1-weighted images and well-defined hyperintensity on T2
      weighted images with marked homogeneous enhancement after contrast material
      administration. We report the characteristic MR imaging observations for these
      lesions.

PMID- 12812944
TI  - Sinonasal intestinal-type adenocarcinoma involvement of the paranasal sinuses.
AB  - We present a patient with a biopsy-proved sinonasal intestinal-type
      adenocarcinoma who presented with moderate confusion. He was found to have
      bifrontal hemorrhages, which to our knowledge has not been previously described
      in the literature for this entity. Intestinal-type adenocarcinoma should be in
      the differential diagnosis of aggressive lesions in the base of the skull with
      intracranial spread from the paranasal sinuses.

PMID- 12812945
TI  - Alveolar soft-part sarcoma of the tongue.
AB  - Alveolar soft-part sarcoma is a rare, aggressive malignancy of uncertain
      histologic origin with a propensity for vascular invasion and distant metastasis.
      This neoplasm may mimic benign vascular neoplasms or malformations but careful
      evaluation of the unique imaging features on CT scans, MR images, and angiograms
      lead to the correct diagnosis. We present a case of alveolar soft-part sarcoma of
      the tongue and emphasize its radiologic and clinical features.

PMID- 12812946
TI  - Chronic submasseteric abscess: anatomic, radiologic, and pathologic features.
AB  - Herein we present five cases of submasseteric abscess that most commonly occurred
      in patients with a history dental disease. CT has been the main imaging method
      for diagnosing lesions in the masticator space and adjacent to the mandible;
      however, we found that, in some of our cases, CT defined the lesion poorly or not
      at all. In some cases, MR imaging defined the lesion better. Radiologic
      manifestations of this condition and pathologic correlations are discussed.

PMID- 12812947
TI  - Teflon-induced granuloma: a false-positive finding with PET resolved with
      combined PET and CT.
AB  - Patients who have undergone thyroidectomy may have recurrent laryngeal nerve
      injury; until recently, Teflon injection was commonly used for vocal cord
      medialization. We present a case of a patient who underwent thyroidectomy who had
      significantly increased and unilateral (18)F-fluorodeoxyglucose uptake in the
      neck, which was found to be localized to the left vocal cord by use of combined
      positron emission tomography (PET) and CT, presumably because of a Teflon-induced
      granuloma. Knowledge of this potential source of false-positive PET
      interpretation because of its inability to precisely localize neoplastic lesions,
      and the use of combined PET and CT imaging, may allow precise diagnosis and
      prevention of unnecessary interventions.

PMID- 12812948
TI  - Intracanalicular optic nerve meningioma: a serious diagnostic pitfall.
AB  - We describe six cases of cannalicular optic nerve meningioma in which the
      diagnosis was missed for more than 1 year after the onset of symptoms. Clinical
      features led to a misdiagnosis of optic neuritis in all cases. Although atypical
      clinical progression led to further imaging studies, they did not provide the
      diagnosis because of inappropriate imaging protocols. Diagnosis was eventually
      made on the basis of high-spatial-resolution contrast-enhanced MR findings.
      Radiologists should have a high suspicion for the diagnosis of optic canal
      meningioma in patients with unexplained visual loss, particularly when visual
      loss is progressive. Investigation in these cases should include high-spatial
      resolution MR imaging of the orbit before and after contrast medium
      administration, and fat suppression should be used in combination with contrast
      enhancement whenever possible.

PMID- 12812949
TI  - Diffusion imaging in obstructive hydrocephalus.
AB  - BACKGROUND AND PURPOSE: Hydrocephalus causes transependymal resorption of spinal
      fluid that in turn produces periventricular interstitial edema. This study was
      performed to determine if diffusion imaging can demonstrate this interstitial
      edema in the periventricular region in patients with obstructive hydrocephalus
      and if it can be used to assess the treatment response. METHODS: Twenty-one
      patients with obstructive hydrocephalus were evaluated with MR diffusion imaging
      before and after treatment. The change in ventricular size was measured by using
      the frontal and occipital horn ratio. The signal intensity abnormalities in
      periventricular white matter were scored. Average diffusion constants (D(av)) in
      the periventricular white matter were measured before and after treatment and
      compared with normal values. Post-treatment resolution of MR imaging
      abnormalities and changes in ventricular volume were compared with changes in
      D(av). RESULTS: D(av) measured from periventricular white matter was increased in
      hydrocephalic patients compared with age-matched control subjects by a mean of
      6.9% (P <.02). After treatment, D(av) decreased by an average of 6.0%: D(av)
      decreased in 11 patients (53%), it remained essentially unchanged in seven (33%),
      and it increased in three (14%). CONCLUSION: For patients with obstructive
      hydrocephalus, diffusion is usually increased in the periventricular white
      matter. Therefore, increased D(av) may be a clinically useful sign of
      hydrocephalus, and it may prove useful in cases with equivocal clinical or
      imaging findings. Measurement of D(av) may be valuable in assessing the treatment
      response in these patients because D(av) usually decreases toward normal levels
      with successful treatment.

PMID- 12812950
TI  - MR imaging and spectroscopy of a tuber cinereum hamartoma in a patient with
      growth hormone deficiency and hypogonadotropic hypogonadism.
AB  - To our knowledge, this is the first report of hypogonadotropic hypogonadism, or
      growth hormone deficiency, in a patient without non-Pallister-Hall syndrome who
      had hypothalamic hamartoma diagnosed on the basis of MR imaging and MR
      spectroscopy findings. On short-TE proton MR spectra, the N-acetylaspartate
      concentration in the hamartoma was lower than that in the thalamus but similar to
      that in the amygdala. However, myo-inositol concentration was elevated in the
      hamartoma compared with that in the amygdala and thalamus. This report stresses
      the advantages of short-TE spectroscopy and demonstrates that regional variations
      in spectra should be considered when reference structures are used.

PMID- 12812951
TI  - Diffusion-weighted MR imaging in neonatal nonketotic hyperglycinemia.
AB  - To our knowledge, we are the first to report the diffusion-weighted MR imaging
      findings in a 15-day-old neonate with nonketotic hyperglycinemia. We found
      bilaterally symmetrical lesions of restricted diffusion in the dorsal brain stem,
      cerebral peduncles, and posterior limbs of the internal capsule, which were more
      conspicuous and extensive on diffusion-weighted MR images than on T2-weighted
      images. These lesions are in the myelinated tracts of the neonate and are
      compatible with the expected sites of abnormality in vacuolating myelinopathy.

PMID- 12812952
TI  - Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from
      proximal urea cycle disorders.
AB  - We present brain MR images in three patients with neonatal-onset hyperammonemic
      encephalopathy resulting from urea-cycle disorders (two sisters with deficiency
      of the carbamyl phosphate synthetase I reaction step and one boy with an
      ornithine transcarbamylase deficiency). MR imaging revealed almost identical
      findings of injury to the bilateral lentiform nuclei and the deep sulci of the
      insular and perirolandic regions; to our knowledge, this pattern has not been
      previously reported. We hypothesize that these lesions presumably reflect the
      distribution of brain injury due to hypoperfusion secondary to hyperammonemia and
      hyperglutaminemia in the neonatal period.

PMID- 12812953
TI  - Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings.
AB  - Mutations in the nuclear SURF1 gene are specifically associated with cytochrome c
      oxidase (COX)-deficient Leigh syndrome. MR imaging abnormalities in three
      children with this condition involved the subthalamic nuclei, medulla, inferior
      cerebellar peduncles, and substantia nigra in all cases. The dentate nuclei and
      central tegmental tracts were involved in two cases each (all instances), and the
      putamina, interpeduncular nucleus, and pallido-cortical-nigro-cortical tracts in
      one. MR imaging pattern recognition can suggest an underlying COX deficiency and
      should prompt investigators to search for SURF1 gene mutations.

PMID- 12812954
TI  - Treatment of wide-necked intracranial aneurysms with a self-expanding stent
      system: initial clinical experience.
AB  - BACKGROUND AND PURPOSE: Currently available stents for intracranial use usually
      are balloon-expandable coronary stents that carry the risk of damaging a
      dysplastic segment of the artery, with potential vessel rupture. We assessed the
      technical feasibility and efficacy of the combined application of a flexible,
      self-expanding neurovascular stent and detachable coils in the management of wide
      necked intracranial aneurysms in humans. METHODS: Four consecutive patients with
      a wide-necked intracranial aneurysm were treated with a combined approach that
      consisted of delivery of a flexible self-expanding neurovascular stent through a
      microcather to cover the neck of the aneurysm and subsequent filling of the
      aneurysm with coils through the stent interstices. The aneurysms were located at
      the internal carotid artery (n=2) and the basilar tip encroaching the P1 segment
      (n=2). Previous attempts with conventional endosaccular coil packing alone failed
      in all cases. RESULTS: Stent placement in the desired position with complete or
      nearly complete occlusion of the aneurysms was feasible in all patients. In one
      patient, aneurysm perforation with the microcatheter occurred and necessitated
      ventricular drainage, which led to a large parenchymal and intraventricular
      hemorrhage because of the strong anticoagulation regimen. Six-month follow-up
      demonstrated no focal neurologic sequelae in any of the patients, except slight
      memory dysfunction in the patient with bleeding. CONCLUSION: Preliminary data
      demonstrate that this extremely flexible stent is technically easy to deploy and
      can be easily and safely maneuvered through severely tortuous vessels, enabling
      the treatment of intracranial wide-necked aneurysms. The combination of
      endovascular reconstruction of the parent vessel with use of a self-expanding
      stent followed by coil embolization offers a promising therapeutic alternative
      for wide-necked aneurysms not amenable to coil embolization alone. Although
      immediate angiographic results are promising, long-term angiographic and clinical
      follow-up is essential to determine permanent vessel patency and aneurysm
      occlusion rate.

PMID- 12812955
TI  - Symptomatic cavernous sinus aneurysms: management and outcome after carotid
      occlusion and selective cerebral revascularization.
AB  - BACKGROUND AND PURPOSE: Therapeutic internal carotid artery (ICA) occlusion for
      symptomatic intracavernous artery aneurysms can result in ischemic infarction
      despite normal clinical balloon test occlusion (BTO). We evaluated outcomes in
      patients with symptomatic cavernous sinus aneurysms in whom clinical BTO was
      normal, who underwent carotid occlusion with selective bypass surgery guided by
      physiologic BTO using quantitative cerebral blood flow (CBF) analysis by means of
      stable xenon-enhanced CT. METHODS: After a normal clinical BTO, 26 consecutive
      patients with symptomatic cavernous sinus aneurysms underwent a baseline xenon
      enhanced CT CBF analysis followed by a second CBF analysis, during which repeat
      BTO was performed. Patients with a decrease in cortical CBF to below 30 mL/100
      g/min were considered moderate risk and those with greater than 30 mL/100 g/min
      were low risk for developing postocclusion ischemic infarction. Moderate-risk
      patients underwent cerebral revascularization followed by proximal carotid
      occlusion. Low-risk patients underwent carotid occlusion alone. Patients were
      clinically followed up for at least 3 months after carotid occlusion. All
      patients underwent head CT at least 1 month after carotid occlusion. RESULTS:
      Eight patients were moderate risk and 18 low risk. Mean follow-up was 15.3
      months. Mean CT follow-up was 10.2 months. No low-risk patient developed a
      postocclusion ischemic deficit by examination or infarct by CT. One patient in
      the moderate-risk group developed right hemiparesis and a left posterior middle
      cerebral artery infarction by CT 2 months after carotid occlusion. CONCLUSION: In
      this series, BTO combined with quantitative CBF analysis was a safe and reliable
      technique for identification of patients at risk for ischemic infarction after
      carotid occlusion, despite a normal clinical BTO.

PMID- 12812956
TI  - Endovascular treatment of peripheral cerebellar artery aneurysms.
AB  - BACKGROUND AND PURPOSE: Peripheral cerebellar artery aneurysms are rare and
      difficult to treat surgically. We report the angiographic results and the
      clinical outcomes for eight patients treated by embolization for peripheral
      cerebellar artery aneurysms. METHODS: Between 1994 and 2001, eight patients with
      peripheral cerebellar artery aneurysms were referred from the neurosurgery
      department for endovascular treatment. The patients consisted of four women and
      four men with a mean age of 43 years (range, 16-68 years). Seven patients
      presented with subarachnoid hemorrhage. In one patient, the aneurysm was
      incidental. In five cases, selective embolization of the aneurysmal sac was
      performed using GDCs. Two large peripheral cerebellar artery aneurysms and one
      small aneurysm with a wide neck were treated by parent vessel occlusion. Mean
      clinical and imaging follow-up duration was 18.5 months (range, 12-36 months).
      RESULTS: Endovascular treatment resulted in five complete occlusions, two neck
      remnants, and one residual aneurysmal flow. Clinical evaluation showed that good
      or excellent recovery was achieved by all patients. Imaging follow-up revealed
      seven complete occlusions and one residual aneurysmal flow. CONCLUSION: Our study
      showed that the endovascular approach to treat peripheral cerebellar artery
      aneurysms by selective embolization or parent vessel occlusion was feasible,
      safe, and effective. Imaging follow-up showed excellent anatomic results in
      accordance with clinical recovery.

PMID- 12812957
TI  - Alginate for endovascular treatment of aneurysms and local growth factor
      delivery.
AB  - BACKGROUND AND PURPOSE: Coil embolization is safe and effective but may be
      followed by aneurysm recurrence. Our purpose was to explore the use of alginate
      as a new embolic agent that could deliver growth factors and improve results of
      endovascular treatment of aneurysms. METHODS: We first assessed the potential of
      alginate as a vector for growth factor delivery by using in vitro binding and
      elution studies. Lateral wall (n = 68) and bifurcation (n = 4) aneurysms were
      then constructed in six pigs and 36 dogs. We explored iodine-125 transforming
      growth factor-beta(1) in vivo alginate delivery in 16 canine aneurysms. We next
      assessed the effects of adding alginate to gelatin sponges on angiographic and
      pathologic results at 3 weeks (n = 4 each) in an established model used for the
      study of recanalization and recurrence. We then explored techniques to control
      endovascular alginate delivery without protection (n = 4), with the protection of
      a balloon (n = 4), and with the protection of a single coil (n = 12) at the
      aneurysm neck in 12 porcine aneurysms, four canine lateral wall aneurysms, and
      four canine bifurcation aneurysms. The stability of cross-linked alginate was
      studied after intraoperative injections in eight aneurysms. Finally, to determine
      the value of the material with or without growth factor in promoting aneurysm
      healing, we compared angiographic results and neointima formation 3 weeks after
      intraoperative embolization of canine lateral wall aneurysms with alginate blocks
      with or without platelet-derived growth factor-BB or transforming growth factor
      beta(1) (n = 5 each). RESULTS: Growth factors rapidly eluted from alginate in
      vitro and in vivo. Alginate coating of sponges led to improved angiographic
      results and thick neointima formation. Intraoperative alginate block embolization
      did not lead to recurrence, and growth factors delivered with alginate did not
      show added benefits. Endovascular alginate embolization was complicated by
      carotid emboli, and the polymer was unstable once injected, causing delayed
      neurologic deficits. CONCLUSION: Growth factor delivery can be performed with
      alginate, but formulation changes and improved endovascular control are necessary
      before contemplating its use in intracranial aneurysms.

PMID- 12812958
TI  - Balloon-assisted coil placement in wide-neck bifurcation aneurysms by use of a
      new, compliant balloon microcatheter.
AB  - Two types of balloon are usually employed to perform balloon-assisted coil
      placement in cerebral aneurysms: oval, guide-dependent balloons for sidewall
      aneurysms and round balloons for bifurcation aneurysms. We report on the use of a
      new, more compliant, guide-dependent oval balloon microcatheter to seal wide-neck
      bifurcation aneurysms with coils during endovascular occlusion.

PMID- 12812959
TI  - Basilar trunk occlusion during endovascular treatment of giant and fusiform
      aneurysms of the basilar artery.
AB  - Giant and fusiform aneurysms of the basilar artery (BA) are difficult to manage
      surgically, and they still present a challenge for the neurosurgeon despite
      progress in posterior fossa surgery. Guglielmi detachable coils have provided an
      alternative approach to treatment, but they have their own difficulties. We
      present a series of three patients with BA aneurysms treated with endovascular
      occlusion of the aneurysm and basilar trunk. Our experience suggests that, in
      select cases, BA occlusion may be not only safe but also necessary for the
      effective treatment of these aneurysms.

PMID- 12812960
TI  - Direct percutaneous puncture of a cervical internal carotid artery aneurysm for
      coil placement after previous incomplete stent-assisted endovascular treatment.
AB  - Direct percutaneous puncture for coil placement has been described for visceral
      aneurysms, but the procedure has not been previously reported for aneurysms of
      the head and neck. We report a case in which stent-assisted endovascular
      treatment was successfully combined with direct puncture for additional coil
      placement to treat a symptomatic giant aneurysm of the cervical internal carotid
      artery.

PMID- 12812961
TI  - Successful treatment of cerebral vasospasm by use of transdermal nitroglycerin
      ointment (Nitropaste).
AB  - To our knowledge, the use of transdermal nitroglycerin ointment (Nitropaste) in
      the setting of intracranial vasospasm has not been described in the peer-reviewed
      literature. Five patients with intracranial vasospasm induced by subarachnoid
      hemorrhage were evaluated angiographically both before and after application of
      Nitropaste. All cases exhibited mild to moderate improvement in the degree of
      vasospasm. We conclude that Nitropaste is a simple noninvasive technique to
      reduce intracranial vasospasm.

PMID- 12812962
TI  - Acute vasogenic edema induced by thrombosis of a giant intracranial aneurysm: a
      cause of pseudostroke after therapeutic occlusion of the parent vessel.
AB  - A 16-year-old male adolescent presenting with acute retro-orbital pain underwent
      emergent internal carotid occlusion for a giant cavernous aneurysm. Three weeks
      later, the patient complained of headache and right hemiparesis, which suggested
      an acute stroke. CT and MR imaging revealed vasogenic brain edema without
      infarct. The symptoms rapidly resolved with steroid therapy. Follow-up CT showed
      resolution of the edema. The imaging characteristics, clinical implications, and
      etiology of vasogenic edema occurring after thrombosis of a giant intracranial
      aneurysm are discussed.

PMID- 12812963
TI  - Cavernous sinus dural fistulae treated by transvenous approach through the facial
      vein: report of seven cases and review of the literature.
AB  - BACKGROUND AND PURPOSE: Dural Carotid Cavernous Fistulas (CCFs) can be treated by
      transarterial and/or transvenous endovascular techniques. The venous route
      usually goes through the internal jugular vein (IJV) and the inferior petrosal
      sinus (IPS) up to the pathologic shunts of the cavernous sinus. In case a
      thrombosed IPS, catheterization through the obstructed sinus is not always
      possible and a puncture of the superior ophthalmic vein (SOV) can be performed
      often after a surgical approach. We report our results in the endovascular
      transvenous treatment of dural CCFs through the facial vein (retrograde
      catheterization of the IJV, facial vein, angular vein, SOV, and cavernous sinus).
      METHODS: A retrospective study of seven patients with a dural CCF treated with
      transvenous embolization via the facial vein was performed. In five patients, the
      IPS was thrombosed. In one patient, the IPS was patent, but there was not
      communication between the cavernous sinus compartment in which the CCF shunts
      were located and the IPS itself. In the only patient with the CCF draining
      through permeable IPS, the transvenous route through the IPS permitted the
      occlusion of the posterior CCF shunts and a second session was performed through
      the facial vein in order to occlude the shunts of the anterior compartment of the
      cavernous sinus. The other six patients underwent one embolization session only.
      RESULTS: In all seven cases, it was possible to navigate through the tortuous
      junction of the angular vein and the SOV. In one patient with a thrombosed SOV,
      the venous procedure was interrupted because the catheterization through the
      occluded SOV failed. In the other six patients, after transvenous catheterization
      of the cavernous sinus via the facial vein, placement of coils resulted in
      complete occlusion of the dural CCF with clinical cure in four patients and
      improvement in two. CONCLUSION: In the endovascular treatment of the dural CCFs,
      the transfemoral approach via the facial vein provides a valuable alternative to
      other transvenous routes. Catheterization of the cavernous sinus via the facial
      vein is usually successful. Although this technique requires caution, it allows a
      safe and effective treatment of these lesions.

PMID- 12812964
TI  - Transradial cerebral angiography: technique and outcomes.
AB  - BACKGROUND AND PURPOSE: The transradial approach is routinely used for coronary
      angiography, but only limited data exist regarding transradial cerebral
      angiography. The purpose of this report was to offer detailed procedural methods
      for transradial cerebral angiography to facilitate adoption of the technique.
      METHODS: We reviewed 60 consecutive cases of transradial access used for
      neuroangiography and catalogued the indications for angiography, the sheath size,
      the catheter type, the length of the procedure, the number of cases in which
      radial artery access was unsuccessful, and the complications. We also noted
      procedural details regarding adjunctive medications, preprocedural patient
      assessment, and postprocedural care. RESULTS: Transradial angiography was
      successfully applied in 57 of 60 cases (51 diagnostic, six interventional, three
      failed accesses). Sheaths were used in all cases and ranged in size from 4F to
      6F. Mean procedural time for diagnostic cases was 40 minutes +/- 19 [SD]. Access
      site complications included one forearm hematoma. CONCLUSION: Transradial
      angiography is a useful tool for diagnostic and interventional neuroangiographic
      procedures. All relevant vessels can be accessed from the radial artery for
      diagnostic studies. Interventions in the right vertebral and carotid systems are
      facilitated by the transradial approach.

PMID- 12812965
TI  - Diffusion-weighted imaging of the spine: is it reliable?

PMID- 12812966
TI  - Sensitivity-encoded diffusion tensor MR imaging of the cervical cord.
AB  - The aim of this study was to apply sensitivity-encoding (SENSE) echo-planar
      imaging (EPI) to diffusion tensor MR imaging of the cervical cord, an anatomic
      region where MR imaging is particularly challenging. This technique was
      implemented with a SENSE reduction factor of 2 and used for imaging a water
      phantom and five healthy volunteers. Off-resonance artifacts were notably reduced
      compared with those of full-FOV EPI sequences. This approach to diffusion tensor
      MR imaging of the cervical cord is promising for future, more extensive clinical
      applications.

PMID- 12812967
TI  - Radiation dose to the operator during vertebroplasty: prospective comparison of
      the use of 1-cc syringes versus an injection device.
AB  - BACKGROUND AND PURPOSE: Percutaneous vertebroplasty procedures require relatively
      long durations of fluoroscopic guidance, which might lead to substantial
      radiation dose to operators. Specialized injection devices have been proposed to
      limit operator exposure. Our purpose was to compare the radiation dose to the
      operator's hands during vertebroplasty when using 1-cc syringes versus that when
      using an injection device. METHODS: Radiation dosimeters were worn on the left
      wrist during 39 vertebroplasty injection procedures in 25 patients. Cases were
      alternated between the use of 1-cc syringes (19 procedures) and the use of an
      injection device (20 procedures). For each procedure, one dosimeter was worn
      throughout the procedure, both during needle placement and injection, and a
      second dosimeter was worn during the injection phase only. Mean doses for the
      whole case and mean doses for the injection procedure alone were compared between
      groups. RESULTS: Mean whole case dose was 128 +/- 161 mrem (range, 0-660 mrem)
      for the 1-cc syringe group versus 98 +/- 90 mrem (range, 0-340 mrem) for the
      injection device group (P =.23). Mean dose during injection was 100 +/- 145 mrem
      (range, 0-660 mrem) for the 1-cc syringe group versus 55 +/- 43 mrem (range, 0
      130 mrem) for the injection device group (P =.09). Three of 19 1-cc syringe cases
      yielded zero dose, compared with four of 20 injection device cases. Duration of
      injection was markedly different between groups, with mean injection times of 4.2
      and 7.5 min for 1-cc syringe and injection device cases, respectively (P
      <.00002). Mean injection dose per minute of lateral fluoroscopy was 23.6 and 7.3
      mrem for the 1-cc syringe and injection device groups, respectively (P =.002).
      CONCLUSION: The use of an injection device significantly decreased the radiation
      dose to the operator's extremity per unit time of injection. However, total dose
      per injection was equivalent between groups because of significantly longer
      injection duration for the injection device cohort.

PMID- 12812968
TI  - Spontaneous resolution of an intraspinal synovial cyst.
AB  - We report a case of lumbar facet joint synovial cyst at L5-S1 with clinically
      significant radicular pain diagnosed by means of MR imaging. This cyst
      spontaneously resolved, as determined on follow-up MR images obtained 18 months
      later. The patient's clinical symptoms substantially improved after conservative
      medical treatment.

PMID- 12812969
TI  - Paul F. J. New, MD, FACR.

PMID- 12812975
TI  - CALL interrupted in a patient with non-specific mental retardation: gene dosage
      dependent alteration of murine brain development and behavior.
AB  - Investigation of MR patients with 3p aberrations led to the identification of the
      translocation breakpoint in intron five of the neural Cell Adhesion L1-Like (CALL
      or CHL1) gene in a man with non-specific mental retardation and 46,Y,
      t(X;3)(p22.1;p26.3). The Xp breakpoint does not seem to affect a known or
      predicted gene. Moreover, a fusion transcript with the CALL gene could not be
      detected and no mutations were identified on the second allele. CALL is highly
      expressed in the central and peripheral nervous system, like the mouse ortholog
      'close homolog to L1' (Chl1). Chl1 expression levels in the hippocampus of
      Chl1(+/-) mice were half of those obtained in wild-type littermates, reflecting a
      gene dosage effect. Timm staining and synaptophysin immunohistochemistry of the
      hippocampus showed focal groups of ectopic mossy fiber synapses in the lateral
      CA3 region, outside the trajectory of the infra-pyramidal mossy fiber bundle in
      Chl1(-/-) and Chl1(+/-) mice. Behavioral assessment demonstrated mild alterations
      in the Chl1(-/-) animals. In the probe trial of the Morris Water Maze test, Chl1(
      /-) mice displayed an altered exploratory pattern. In addition, these mice were
      significantly more sociable and less aggressive as demonstrated in social
      exploration tests. The Chl1(+/-) mice showed a phenotypic spectrum ranging from
      wild-type to knockout behavior. We hypothesize that a 50% reduction of CALL
      expression in the developing brain results in cognitive deficits. This suggests
      that the CALL gene at 3p26.3 is a prime candidate for an autosomal form of mental
      retardation. So far, mutation analysis of the CALL gene in patients with non
      specific MR did not reveal any disease-associated mutations.

PMID- 12812976
TI  - Protein kinase-A activity in PRKAR1A-mutant cells, and regulation of mitogen
      activated protein kinases ERK1/2.
AB  - Carney complex (CNC) is caused by PRKAR1A-inactivating mutations. PRKAR1A encodes
      the regulatory subunit type I-alpha (RIalpha) of the cAMP-dependent kinase (PKA)
      holoenzyme; how RIalpha insufficiency leads to tumorigenesis remains unclear. In
      many cells PKA inhibits the extracellular receptor kinase (ERK1/2) cascade of the
      mitogen-activated protein kinase (MAPK) pathway leading to inhibition of cell
      proliferation. We investigated whether the PKA-mediated inhibitory effect on
      ERK1/2 is affected in CNC cells that carry germline PRKAR1A mutations. PKA
      activity both at baseline and after stimulation with cAMP was augmented in cells
      carrying mutations. Quantitative message analysis showed that the main PKA
      subunits expressed were type I (RIalpha and RIbeta) but RIalpha was decreased in
      mutant cells. Immunoblot assays of ERK1/2 phosphorylation by the cell- and
      pathway-specific stimulant lysophosphatidic acid (LPA) showed activation of this
      pathway in a time- and concentration-dependent manner that was prevented by a
      specific inhibitor. There was a greater rate of growth in mutant cells; forskolin
      and isoproterenol inhibited LPA-induced ERK1/2 phosphorylation in normal but not
      in mutant cells. Forskolin inhibited LPA-induced cell proliferation and
      metabolism in normal cells, but stimulated these parameters in mutant cells.
      These data were also replicated in a pituitary tumor cell line carrying the most
      common PRKAR1A mutation (c.578del TG), and an in vitro construct of mutant
      PRKAR1A that was recently shown to lead to augmented PKA-mediated
      phosphorylation. We conclude that PKA activity in CNC cells is increased and that
      its stimulation by forskolin or isoproterenol increases LPA-induced ERK1/2
      phosphorylation, cell metabolism and proliferation. Reversal of PKA-mediated
      inhibition of this MAPK pathway in CNC cells may contribute to tumorigenesis in
      this condition.

PMID- 12812977
TI  - Expansion of the polyQ repeat in ataxin-2 alters its Golgi localization, disrupts
      the Golgi complex and causes cell death.
AB  - Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of a
      polyglutamine (polyQ) repeat in ataxin-2, the SCA2 gene product. In contrast to
      other polyQ diseases, intranuclear inclusions are not prominent in SCA2. In
      animal models with expression of mutant ataxin-2 targeted to Purkinje cells,
      neuronal dysfunction and morphologic changes are observed without the formation
      of intranuclear aggregates. In this report, we investigated the mechanisms
      underlying SCA2 pathogenesis using cellular models. We confirmed that the SCA2
      gene product, ataxin-2, was predominantly located in the Golgi apparatus.
      Deletion of ER-exit and trans-Golgi signals in ataxin-2 resulted in an altered
      subcellular distribution. Expression of full-length ataxin-2 with an expanded
      repeat disrupted the normal morphology of the Golgi complex and colocalization
      with Golgi markers was lost. Intranuclear inclusions were only seen when the
      polyQ repeat was expanded to 104 glutamines, and even then were only observed in
      a small minority of cells. Expression of ataxin-2 with expanded repeats in PC12
      and COS1 cells increased cell death compared with normal ataxin-2 and elevated
      the levels of activated caspase-3 and TUNEL-positive cells. These results suggest
      a link between cell death mediated by mutant ataxin-2 and the stability of the
      Golgi complex. The formation of intranuclear aggregates is not necessary for in
      vitro cell death caused by expression of full-length mutant ataxin-2.

PMID- 12812978
TI  - Transglutaminase potentiates ligand-dependent proteasome dysfunction induced by
      polyglutamine-expanded androgen receptor.
AB  - Expansion of the CAG trinucleotide repeat encoding glutamine in the androgen
      receptor gene leads to spinobulbar muscular atrophy (SBMA), a neurodegenerative
      disorder in a family of polyglutamine diseases with enigmatic pathogenic
      mechanisms. One established property of glutamine residues is their ability to
      act as an amine accepter in a transglutaminase-catalyzed reaction, resulting in a
      proteolytically resistant glutamyl-lysine cross-link. To examine underlying
      disease mechanisms we investigated the relationship between polyglutamine
      expanded androgen receptor and transglutaminase. We found androgen receptor N
      terminal fragments are a substrate for transglutaminase. Western blots of the
      proteins following incubation with transglutaminase show that several different
      epitopes of the AR appear to be lost. We propose that this is due to the
      transglutaminase cross-linking of the AR, which interferes with antibody
      recognition. Furthermore, HEK GFP(u)-1 cells expressing polyglutamine-expanded
      androgen receptor and transglutaminase exhibit ligand-dependent proteasome
      dysfunction; this effect was not observed in the presence of cystamine, a
      transglutaminase inhibitor. In addition, transglutaminase-mediated isopeptide
      bonds were detected in brains of SBMA transgenic mice, but not in controls,
      suggesting involvement of transglutaminase-catalyzed reactions in polyglutamine
      disease pathogenesis. Our hypothesis is that cross-linked AR cannot to be
      degraded by the proteasome and obstructs the proteasome pore, preventing normal
      function. Because of the central role the ubiquitin-proteasome degradation system
      plays in fundamental cellular processes, any alteration in its function could
      cause cell death, ultimately contributing to SBMA pathogenesis.

PMID- 12812979
TI  - True XP group E patients have a defective UV-damaged DNA binding protein complex
      and mutations in DDB2 which reveal the functional domains of its p48 product.
AB  - Xeroderma pigmentosum (XP) is a skin cancer-prone autosomal recessive disease
      characterized by inability to repair UV-induced DNA damage. The major form of XP
      is defective in nucleotide excision repair (NER) and comprises seven
      complementation groups (A-G). The genes defective in all groups have been
      identified unambiguously with the exception of group E. The cells of some XP-E
      patients are deficient in a protein complex (consisting of two subunits:
      p127/DDBI and p48/DDB2) which binds to UV-damaged DNA (UV-DDB) and is
      specifically involved in the removal of photoproducts from the non-transcribed
      regions of the genome. However, other XP-E patients have been reported not to
      lack UV-damaged DNA binding activity (DDB(+)). Here we describe several
      genetically unrelated XP-E patients, not previously analyzed in depth, each
      carrying two mutated alleles for DDB2, causing either a single amino acid change
      or a protein truncation or internal deletion. These defects result in a severe
      decrease of detectable p48 protein, abolish interaction with the p127 subunit,
      and produce a deficiency in UV-DDB binding activity (DDB(-)). The role of p48 in
      the repair defect of these patients was demonstrated in vivo and in vitro.
      Investigation of four DDB(+) cell strains from patients previously assigned to XP
      E, allowed us to reclassify all of them into other groups and to show that they
      do not share the molecular and biochemical features typical for XP-E. Besides
      confirming that the true XP-E phenotype is DDB(-), resulting from defects in a
      single gene, DDB2, our results identify the functional domains of the
      corresponding p48 protein.

PMID- 12812980
TI  - The Menkes disease ATPase (ATP7A) is internalized via a Rac1-regulated, clathrin-
      and caveolae-independent pathway.
AB  - The Menkes disease gene encodes a P-type transmembrane ATPase (ATP7A) that
      translocates cytosolic copper ions across intracellular membranes of compartments
      along the secretory pathway. ATP7A moves from the trans-Golgi network (TGN) to
      the cell surface in response to exogenously added copper ions and recycles back
      to the TGN upon copper removal. The protein contains a C-terminal di-leucine
      motif necessary for internalization from the cell surface. In this study we show
      that ATP7A is internalized by a novel pathway that is independent of clathrin
      mediated endocytosis. Expression of dominant-negative mutants of the dynamin-I,
      dynamin-II and Eps15 proteins that block clathrin-dependent endocytosis of the
      transferrin receptor do not inhibit internalization of endogenous ATP7A, or an
      ATP7A reporter molecule (CD8-MCF1). Similarly, inhibitors of caveolae-mediated
      uptake do not affect ATP7A internalization whilst preventing uptake of PODIPY
      ganglioside GM(1), a caveolae marker. In contrast, expression of a constitutively
      active mutant of the Rac1 GTPase inhibits plasma membrane internalization of both
      the ATP7A and transferrin receptor transmembrane proteins. These findings define
      a novel route required for ATP7A internalization and delivery to endosomes.

PMID- 12812981
TI  - Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-Jun NH2
      terminal kinase.
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is a dominant-inherited
      neurodegenerative disease characterized by selective cell loss in particular
      neuronal pathways. This is caused by expansion of CAG repeats in the coding
      region of the DRPLA gene, and the extended polyglutamine tract (polyQ) confers a
      toxic activity. It is valuable to characterize disease gene products for
      elucidation of the mechanism underlying neuron death at specific anatomical areas
      of the brain. Here, we define the DRPLA protein as a phosphoprotein, and c-Jun
      NH(2)-terminal kinase (JNK) is one of the major factors involved in its
      phosphorylation. Endogenous DRPLA protein was serine-phosphorylated.
      Phosphorylation was demonstrated in a recombinant JNK activation system in vitro
      and also in overexpressing cells by transfection after the JNK activation with
      osmotic pressure. One of the phospho-acceptor sites for JNK appearing in the
      DRPLA sequence was indeed phosphorylated, which was confirmed by a specific
      antibody raised against the phosphopeptide. Kinetic studies in the JNK
      recombinant system showed that expanded polyQ slightly reduced the affinity of
      JNK to the protein. Thus, the abnormal DRPLA protein seems to be slowly
      phosphorylated in a certain condition of JNK activation in patients. It may delay
      a process that is essential in keeping neurons alive.

PMID- 12812982
TI  - Targeted inactivation of dystrophin gene product Dp71: phenotypic impact in mouse
      retina.
AB  - The abnormal retinal neurotransmission observed in Duchenne muscular dystrophy
      (DMD) patients and in some genotypes of mice lacking dystrophin has been
      attributed to altered expression of short products of the dystrophin gene. We
      have investigated the potential role of Dp71, the most abundant C-terminal
      dystrophin gene product, in retinal electrophysiology. Comparison of the scotopic
      electroretinograms (ERG) between Dp71-null mice and wild-type (wt) littermates
      revealed a normal ERG in Dp71-null mice with no significant changes of the b-wave
      amplitude and kinetics. Analysis of DMD gene products, utrophin and dystrophin
      associated proteins (DAPs), showed that Dp71 and utrophin were localized around
      the blood vessels, in the ganglion cell layer (GCL), and the inner limiting
      membrane (ILM). Dp71 deficiency was accompanied by an increased level of utrophin
      and decreased level of beta-dystroglycan localized in the ILM, without any
      apparent effect on the other DAPs. Dp71 deficiency was also associated with an
      impaired clustering of two Muller glial cell proteins-the inwardly rectifying
      potassium channel Kir4.1 and the water pore aquaporin 4 (AQP4). Immunostaining of
      both proteins decreased around blood vessels and in the ILM of Dp71-null mice,
      suggesting that Dp71 plays a role in the clustering and/or stabilization of the
      two proteins. AQP4 and Kir4.1 may also be involved in the regulation of the
      ischemic process. We found that a transient ischemia resulted in a greater damage
      in the GCL of mice lacking Dp71 than in wt mice. This finding points at a crucial
      role played by Dp71 in retinal function.

PMID- 12812983
TI  - Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease.
AB  - An expanded CAG repeat is the underlying genetic defect in Huntington disease, a
      disorder characterized by motor, psychiatric and cognitive deficits and striatal
      atrophy associated with neuronal loss. An accurate animal model of this disease
      is crucial for elucidation of the underlying natural history of the illness and
      also for testing experimental therapeutics. We established a new yeast artificial
      chromosome (YAC) mouse model of HD with the entire human HD gene containing 128
      CAG repeats (YAC128) which develops motor abnormalities and age-dependent brain
      atrophy including cortical and striatal atrophy associated with striatal neuronal
      loss. YAC128 mice exhibit initial hyperactivity, followed by the onset of a motor
      deficit and finally hypokinesis. The motor deficit in the YAC128 mice is highly
      correlated with striatal neuronal loss, providing a structural correlate for the
      behavioral changes. The natural history of HD-related changes in the YAC128 mice
      has been defined, demonstrating the presence of huntingtin inclusions after the
      onset of behavior and neuropathological changes. The HD-related phenotypes of the
      YAC128 mice show phenotypic uniformity with low inter-animal variability present,
      which together with the age-dependent striatal neurodegeneration make it an ideal
      mouse model for the assessment of neuroprotective and other therapeutic
      interventions.

PMID- 12812984
TI  - Familial aggregation of abnormal methylation of parental alleles at the IGF2/H19
      and IGF2R differentially methylated regions.
AB  - Loss of imprinting (LOI) has been observed in many types of human tumors and may
      be a predisposing event in some colon cancers. LOI is strongly associated with
      alteration of normal DNA methylation patterns in differentially methylated
      regions (DMRs) of affected loci but it is not known whether LOI is caused by
      stochastic, environmental or genetic factors. We have developed a simple,
      quantitative assay for measurement of allelic methylation ratios based on
      methylation-sensitive restriction endonuclease digestion of genomic DNA and 'hot
      stop' PCR. We examined allelic methylation ratios at DMRs within the IGF2/H19-
      and IGF2R-loci in a panel of 48 three-generation families. We observed familial
      clustering of individuals with abnormal methylation ratios at the IGF2/H19 DMR,
      as well as stability of this trait over a period of nearly two decades,
      consistent with the possibility that constitutional LOI at this locus is due
      largely to genetic factors. At the IGF2R DMR, we observed more variability in the
      allelic methylation ratios over time but also observed familial clustering of
      abnormal methylation ratios. Overall, our observations at IGF2R suggest that
      shared genetic factors are responsible for a major fraction of inter-individual
      variability in parental origin-dependent epigenetic modifications. However,
      temporal changes also occur in isolated cases, as well as within multiple
      individuals in the same family, indicating that environmental factors may also
      play a role.

PMID- 12812985
TI  - Genetic modifiers interact with maternal determinants in vascular development of
      Tgfb1(-/-) mice.
AB  - The transforming growth factor beta signaling family is a key player in genetic
      and multifactorial diseases, including hereditary hemorrhagic telangiectasia
      (HHT), cancer, atherosclerosis and immunomodulation. HHT types 1 and 2 are caused
      by loss of function mutations in ENG and ACVRL1; polymorphisms in TBRI and TGFB1
      are also associated with altered risks for cancer and cardiovascular diseases.
      There is therefore much interest in identifying factors that influence
      transforming growth factor beta1 (TGFbeta1) action in vivo. Here we identify a
      potent modifier locus, Tgfbkm2(129) (LOD=10.5, chromosome 1), that contributes
      over 90% of the genetic component determining survival to birth of Tgfb1(-/-)
      embryos in crosses between C57 and 129 mice, plus a suggestive modifier locus on
      chromosome 17 (LOD=3.7). Tgfb1(-/-) survival to birth (STB), in addition to
      dependence on embryonic Tgfbkm2 genotype, also depends on maternal effects. Fetal
      genotype and maternal factors interact to prevent Tgfb1(-/-) embryonic death due
      to defective yolk sac angiogenesis. C57 or C57/129.F1 mothers support high Tgfb1(
      /-) STB rates, whereas 129 mothers do not. Strain differences in circulating
      maternal TGFbeta1 levels were excluded as the cause of this directional
      complementation. However, strong genetic support is provided for the involvement
      of maternal STB alleles of mitochondrial or imprinted genes that are only
      expressed when passed through the female lineage. Molecular identification of the
      functional gene(s) encoding Tgfbkm2 and its interacting maternal factors will be
      central to an understanding of the mode of action of TGFbeta1 in cardiovascular
      development.

PMID- 12812986
TI  - DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that
      interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction
      with mutation.
AB  - Disrupted-In-Schizophrenia 1 (DISC1) is a novel gene associated with
      schizophrenia by multiple genetic studies. In order to determine how mutations in
      DISC1 might cause susceptibility to schizophrenia, we undertook a comprehensive
      study of the cellular biology of DISC1 in its full-length and disease-associated
      mutant forms. DISC1 interacts by yeast two-hybrid, mammalian two-hybrid, and co
      immunoprecipitation assays with multiple proteins of the centrosome and
      cytoskeletal system, including MIPT3, MAP1A and NUDEL; proteins which localize
      receptors to membranes, including alpha-actinin2 and beta4-spectrin; and proteins
      which transduce signals from membrane receptors, including ATF4 and ATF5.
      Truncated mutant DISC1 fails to interact with ATF4, ATF5 or NUDEL. Deletion
      mapping demonstrated that DISC1 has distinct interaction domains: MAP1A interacts
      via its LC2 domain with the N-terminus of DISC1, whereas MIPT3 and NUDEL bind via
      their C-terminal domains to the central coiled-coil domain of DISC1, and ATF4/5
      bind via their C-terminal domains to the C-terminus of DISC1. In its full-length
      form, DISC1 protein localizes to predominantly perinuclear punctate structures
      which extend into neurites in some cells; mutant truncated DISC1, by contrast, is
      seen in a diffuse pattern throughout the cytoplasm and abundantly in neurites.
      Both forms co-localize with the centrosomal complex, although truncated less
      abundantly than full-length DISC1. Although both full-length and mutant DISC1 are
      found in microtubule fractions, neither form of DISC1 appears to bind directly to
      microtubules, but rather do so in a MIPT3-dependent fashion that is stabilized by
      taxol. Based on these data, we propose that DISC1 is a multifunctional protein
      whose truncation contributes to schizophrenia susceptibility by disrupting
      intracellular transport, neurite architecture and/or neuronal migration, all of
      which have been hypothesized to be pathogenic in the schizophrenic brain.

PMID- 12812987
TI  - Distinct chaperone mechanisms can delay the formation of aggresomes by the
      myopathy-causing R120G alphaB-crystallin mutant.
AB  - A familial form of desmin-related myopathy (DRM) is associated with a missense
      mutation (R120G) in alphaB-crystallin (alphaB) and is characterized by
      intracellular desmin aggregation. Because alphaB is a molecular chaperone that
      participates in the assembly of desmin filaments, it has been suggested that the
      desmin aggregation might be due to the loss of alphaB function. We report here
      that alphaBR120G has indeed impaired in vivo function and structure as reflected
      by a highly reduced capacity to protect cells against heat shock and by an
      abnormal supramolecular organization even in cells not expressing desmin. In many
      cells, alphaBR120G accumulated in inclusion bodies that had characteristics of
      aggresomes concentrating around the centrosome following a microtubule
      facilitated process. Three distinct chaperone mechanisms could reduce or even
      prevent the formation of the alphaBR120G aggresomes. Wild-type alphaB and Hsp27
      prevented aggresome formation by co-oligomerizing with alphaBR120G. Hsp70 with
      its co-chaperone Hdj-1 or Chip-1 but not a mutant of Chip-1 lacking ubiquitin
      ligase activity, reduced the frequency of aggresome formation likely by targeting
      alphaBR120G for degradation. Finally, HspB8 interacted only transiently with
      alphaB but nonetheless rescued the alphaBR120G oligomeric organization,
      suggesting that it acted as a true chaperone assisting in the folding of the
      mutant protein. Hence, the formation of inclusion bodies in alphaBR120G-mediated
      DRM is probably due to the misfolding of alphaBR120G per se and can be delayed or
      prevented by expression of the wild type alphaB allele or other molecular
      chaperones, thereby explaining the adult onset of the disease.

PMID- 12812988
TI  - Nucleocytoplasmic transport signals affect the age at onset of abnormalities in
      knock-in mice expressing polyglutamine within an ectopic protein context.
AB  - In order to better understand the role of nuclear localization of polyglutamine
      in the human CAG repeat disorders, gene targeting was used to add either nuclear
      localization (NLS) or nuclear export (NES) signals to versions of the mouse Hprt
      protein containing expanded polyglutamine (HprtQ150). The NLS increased levels of
      nuclear HprtQ150 protein in the mouse brain and hastened both the presentation of
      neuronal intranuclear inclusions (NIIs) and the onset of behavioral
      abnormalities. The NES reduced levels of nuclear HprtQ150 protein in mouse brain
      and delayed both the presentation of NIIs and the onset of behavioral
      abnormalities. Together these results indicate the nucleus is the primary site of
      toxicity in HprtQ150 mice. Furthermore, the signals did not alter the relative
      regional distribution of NIIs, suggesting that factors other than nuclear access
      dictate the regional specificity of NII formation in this mouse model.

PMID- 12812989
TI  - Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to
      lathosterol 5-desaturase deficiency.
AB  - Lathosterol 5-desaturase catalyzes the conversion of lathosterol to 7
      dehydrocholesterol in the next to last step of cholesterol synthesis. Inborn
      errors of cholesterol synthesis underlie a group of human malformation syndromes
      including Smith-Lemli-Opitz syndrome, desmosterolosis, CHILD syndrome, CDPX2 and
      lathosterolosis. We disrupted the lathosterol 5-desaturase gene (Sc5d ) in order
      to further our understanding of the pathophysiological processes underlying these
      disorders and to gain insight into the corresponding human disorder. Sc5d (-/-)
      pups were stillborn, had elevated lathosterol and decreased cholesterol levels,
      had craniofacial defects including cleft palate and micrognathia, and limb
      patterning defects. Many of the malformations found in Sc5d (-/-) mice are
      consistent with impaired hedgehog signaling, and appear to be a result of
      decreased cholesterol rather than increased lathosterol. A patient initially
      described as atypical SLOS with mucolipidosis was shown to have lathosterolosis
      by biochemical and molecular analysis. We identified a homozygous mutation of
      SC5D (137A>C, Y46S) in this patient. An unique aspect of the lathosterolosis
      phenotype is the combination of a malformation syndrome with an intracellular
      storage defect.

PMID- 12812990
TI  - Role of redox state in modulation of ion channel function by fatty acids and
      phospholipids.

PMID- 12812991
TI  - Intracarotid administration of short-chain alkylglycerols for increased delivery
      of methotrexate to the rat brain.
AB  - 1 The intracarotid administration of alkylglycerols has been reported previously
      by us to be a novel strategy for increased delivery of various chemotherapeutic
      drugs to the normal brain and brain tumors in rats. 2 Effectiveness and structure
      activity relations of the most promising pentyl- and hexylglycerol derivatives
      have been elucidated in vivo by analyzing the transfer of methotrexate (MTX)
      across the blood-brain barrier (BBB) in normal rats. The effects were compared
      with BBB disruption using hypertonic mannitol or intracarotid infusion of
      bradykinin. Furthermore, toxicity of the alkylglycerols has been studied in long
      term experiments. 3 Apart from 1-O-pentyldiglycerol, all alkylglycerols induced a
      concentration-dependent increase in MTX delivery to the brain varying from 1.1 to
      more than 300-fold compared to intra-arterial MTX alone. Enhanced barrier
      permeability rapidly approached baseline values within 5 and 120 min at the
      latest. Chemical structure, concentration, time schedule of injections and
      combination of different alkylglycerols were identified as instruments suited to
      regulate the MTX accumulation within a wide range. Mannitol 1.4 M resulted in
      very high MTX levels in the brain as observed using the highest concentrations of
      alkylglycerols. Intracarotid infusion of bradykinin had only a minor effect on
      the BBB. Using 1-O-pentylglycerol or 2-O-hexyldiglycerol, both cell culture
      experiments and long-term in vivo analyses including clinical, laboratory and
      histopathological evaluations revealed no signs of toxicity. 4 In summary,
      intracarotid short-chain alkylglycerols constitute a very effective and low toxic
      strategy for transient opening of the BBB to overcome the limited access of
      cytotoxic drugs to the brain.

PMID- 12812992
TI  - Agonist- and antagonist-induced sequestration/internalization of neuropeptide Y
      Y1 receptors in HEK293 cells.
AB  - 1 Neuropeptide Y Y(1) receptors are known to internalize following the binding of
      agonists. In the present study, a pseudopeptide Y(1) receptor antagonist,
      homodimeric Ile-Glu-Pro-Dpr-Tyr-Arg-Leu-Arg-Tyr-CONH(2) (GR231118), also induced
      Y(1) receptor internalization in human embryonic kidney (HEK293) cells. 2 We
      demonstrated first that both specifically bound radiolabeled antagonist
      ([(125)I]GR231118) and agonist ([(125)I][Leu(31), Pro(34)]PYY) underwent receptor
      mediated sequestration/internalization in transfected HEK293 cells. 3 Agonist
      induced Y(1) receptor internalization was dependent on clathrin-coated pits and
      was regulated in part by Gi/o-protein activation as revealed by pertussin toxin
      sensitivity. In contrast, antagonist-induced sequestration of Y(1) receptors was
      partly dependent on clathrin-coated pits, but independent from Gi/o-protein
      activation. 4 Exposure to high concentrations of agonist or antagonist caused a
      50 and 75% loss of cell surface binding, respectively. The loss caused by the
      agonist rapidly recovered. This phenomenon was blocked by monensin, an inhibitor
      of endosome acidification, suggesting that cell surface receptor recovery is due
      to recycling. In contrast to the agonist, GR231118 induced a long-lasting
      sequestration of Y(1) receptors in HEK293 cells. 5 Immunofluorescence labeling
      indicated that following 40 min of incubation with either the agonist or the
      antagonist, Y(1) receptors followed markedly different intercellular trafficking
      pathways. 6 Taken together, these findings provided evidence that a pseudopeptide
      Y(1) receptor antagonist can induce long-lasting disappearance of cell surface
      receptors through a pathway distinct from the classical endocytic/recycling
      pathway followed by stimulation with an agonist.

PMID- 12812993
TI  - SB-656104-A, a novel selective 5-HT7 receptor antagonist, modulates REM sleep in
      rats.
AB  - 1 (6-((R)-2-[2-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-ethyl]-pyrrolidine-1
      sulphonyl)-1H-indole hydrochloride) (SB-656104-A), a novel 5-hydroxytryptamine (5
      HT(7)) receptor antagonist, potently inhibited [(3)H]-SB-269970 binding to the
      human cloned 5-HT(7(a)) (pK(i) 8.7+/-0.1) and 5-HT(7(b)) (pK(i) 8.5+/-0.2)
      receptor variants and the rat native receptor (pK(i) 8.8+/-0.2). The compound
      displayed at least 30-fold selectivity for the human 5-HT(7(a)) receptor versus
      other human cloned 5-HT receptors apart from the 5-HT(1D) receptor (
      approximately 10-fold selective). 2 SB-656104-A antagonised competitively the 5
      carboxamidotryptamine (5-CT)-induced accumulation of cyclic AMP in h5
      HT(7(a))/HEK293 cells with a pA(2) of 8.5. 3 Following a constant rate iv
      infusion to steady state in rats, SB-656104 had a blood clearance (CL(b)) of 58+/
      6 ml min(-1) kg(-1) and was CNS penetrant with a steady-state brain : blood ratio
      of 0.9 : 1. Following i.p. administration to rats (10 mg kg(-1)), the compound
      displayed a t(1/2) of 1.4 h with mean brain and blood concentrations (at 1 h
      after dosing) of 0.80 and 1.0 micro M, respectively. 4 SB-656104-A produced a
      significant reversal of the 5-CT-induced hypothermic effect in guinea pigs, a
      pharmacodynamic model of 5-HT(7) receptor interaction in vivo (ED(50) 2 mg kg(
      1)). 5 SB-656104-A, administered to rats at the beginning of the sleep period (CT
      0), significantly increased the latency to onset of rapid eye movement (REM)
      sleep at 30 mg kg(-1) i.p. (+93%) and reduced the total amount of REM sleep at 10
      and 30 mg kg(-1) i.p. with no significant effect on the latency to, or amount of,
      non-REM sleep. SB-269970-A produced qualitatively similar effects in the same
      study. 6 In summary, SB-656104-A is a novel 5-HT(7) receptor antagonist which has
      been utilised in the present study to provide further evidence for a role for 5
      HT(7) receptors in the modulation of REM sleep.

PMID- 12812994
TI  - Anti-inflammatory activity of creatine supplementation in endothelial cells in
      vitro.
AB  - 1 Creatine (CR) supplementation augments muscle strength in skeletal muscle cells
      by increasing intracellular energy pools. However, the effect of CR
      supplementation on endothelial cells remains to be clarified. 2 In this study, we
      investigated whether CR supplementation had any anti-inflammatory activity
      against human pulmonary endothelial cells in culture. 3 We confirmed that
      supplementation with 0.5 mM CR significantly increased both intracellular CR and
      phosphocreatine (PC) through a CR transporter while keeping intracellular ATP
      levels constant independent of CR supplementation and a CR transporter
      antagonist. 4 In the assay system of endothelial permeability, supplementation
      with 5 mM CR significantly suppressed the endothelial permeability induced by
      serotonin and H(2)O(2). 5 In cell adhesion experiments, supplementation with 5 mM
      CR significantly suppressed neutrophil adhesion to endothelial cells. 6 In the
      measurement of adhesion molecules, CR supplementation with more than 0.5 mM CR
      significantly inhibited the expressions of ICAM-1 and E-selectin on endothelial
      cells, and the inhibition was significantly suppressed by an adenosine A(2A)
      receptor antagonist. 7 The present study suggests that CR supplementation has
      anti-inflammatory activities against endothelial cells.

PMID- 12812995
TI  - A role of protein kinase C mu in signalling from the human adenosine A1 receptor
      to the nucleus.
AB  - 1 Stimulation of adenosine A(1) receptors produced a stimulation of c-fos
      promoter-regulated gene transcription in Chinese hamster ovary (CHO)-A1 cells
      expressing the human A(1) receptor. Gene transcription was monitored using a
      luciferase-based reporter gene (pGL3). 2 This response to the A(1) receptor
      agonist N(6)-cyclopentyladenosine (CPA) was sensitive to inhibition by pertussis
      toxin, the MEK-1 inhibitor PD 98059 and by the phosphatidylinositol-3-kinase
      inhibitors wortmannin and LY 294002. The response was also completely abolished
      by the protein kinase C (PKC) inhibitor Ro-31-8220. 3 Several isoforms of PKC can
      be detected in CHO-A1 cells (alpha, delta, epsilon, micro, iota, zeta), but only
      PKC alpha, PKC delta and PKC were downregulated by prolonged treatment with
      phorbol ester. The c-fos-regulated luciferase response to A(1) agonists was not,
      however, inhibited by 24 h pretreatment with the phorbol esters phorbol 12,13
      dibutyrate (PDBu). This observation, together with the fact that a significant
      attenuation (40%) of the c-fos-luciferase response to PDBu and A(1) agonist was
      produced by low concentrations of the PKC inhibitor Go 6976 suggests a role for
      PKC micro. 4 Stimulation of CHO-A1 cells with CPA stimulated the activation of
      endogenous PKC micro as measured by autophosphorylation. This was rapid, occurred
      within 1-2 min, but returned to basal levels after 30 min. Furthermore, transient
      expression of a constitutively active form of PKC micro resulted in a significant
      increase in c-fos-regulated gene expression. 5 Taken together, these data suggest
      that PKC micro plays an important role in the ability of the adenosine A(1)
      receptor to signal to the nucleus.

PMID- 12812996
TI  - Role of PAF receptors during intestinal ischemia and reperfusion injury. A
      comparative study between PAF receptor-deficient mice and PAF receptor antagonist
      treatment.
AB  - 1 The reperfusion of ischemic tissues may be associated with local and systemic
      inflammation that prevents the full benefit of blood flow restoration. The
      present study aimed to confirm a role for platelet-activating factor receptor(s)
      (PAFR) during ischemia and reperfusion injury by using genetically modified mice
      deficient in the PAFR (PAFR(-/-) mice) and to evaluate comparatively the
      effectiveness of pharmacological treatment using the PAFR antagonist UK-74,505
      (modipafant). 2 The reperfusion of the ischemic superior mesenteric artery (SMA)
      induced marked local (intestine) and remote (lungs) tissue injury, as assessed by
      the increase in vascular permeability, neutrophil influx and intestinal
      hemorrhage and in the production of TNF-alpha. There was also a systemic
      inflammatory response, as shown by the increase in serum TNF-alpha concentrations
      and marked reperfusion-associated lethality. 3 After reperfusion of the ischemic
      SMA, PAFR(-/-) mice had little tissue or systemic inflammation and lethality was
      delayed, but not prevented, in these mice. Interestingly, the reperfusion
      associated increases in tissue concentrations of IL-10 were significantly greater
      in PAFR(-/-) than wild-type mice. 4 Pretreatment with PAFR antagonist UK-74,505
      (1 mg kg(-1)) markedly prevented tissue injury, as assessed by the increase in
      vascular permeability, neutrophil accumulation, hemorrhage and TNF-alpha
      concentrations in the intestine and lungs. In contrast, UK-74,505 failed to
      affect reperfusion-associated lethality and increases in serum TNF-alpha when
      used at 1 mg kg(-1). 5 Reperfusion-associated lethality and increase in serum TNF
      alpha were only affected when a supra-maximal dose of the antagonist was used (10
      mg kg(-1)). At this dose, UK-74,505 also induced a marked enhancement of
      reperfusion-associated increases in tissue concentrations of IL-10. However, at
      the same dose, UK-74,505 failed to prevent reperfusion-associated lethality in
      PAFR(-/-) mice any further. 6 The present studies using genetically modified
      animals and a receptor antagonist firmly establish a role of PAFR activation for
      the local, remote and systemic inflammatory injury and lethality which follows
      reperfusion of the ischemic SMA in mice. Moreover, it is suggested that high
      doses of PAFR antagonists need to be used if the real efficacy of these compounds
      is to be tested clinically.

PMID- 12812997
TI  - Actions of tramadol on micturition in awake, freely moving rats.
AB  - 1 (+/-)-Tramadol, a widely used analgesic, is a racemate stimulating opioid
      receptors and inhibiting reuptake of noradrenaline and serotonin, that is,
      pharmacological principles previously shown to influence rat micturition. 2 We
      studied both (+/-)-tramadol and its enantiomers in conscious Sprague-Dawley rats
      undergoing continuous cystometry. The effects of these agents were compared to
      those of morphine ( micro -opioid receptor agonist) and tested after pretreatment
      with naloxone ( micro -opioid receptor antagonist). Cystometries were evaluated
      before and after intravenous (i.v.), intraperitoneal (i.p.) and intrathecal
      (i.t.) drug administrations. 3 The most conspicuous effects of i.v. (+/-)
      tramadol (0.1-10 mg kg(-1)) was an increase in threshold pressure and an increase
      in micturition volume. 4 These effects were mimicked by (+)-tramadol (0.1-5 mg
      kg(-1) i.v.), whereas (-)-tramadol (5 mg kg(-1) i.v.) did not influence threshold
      pressure and micturition volume. 5 The effects of (+/-)-tramadol 5 mg kg(-1) on
      micturition volume were blocked by pretreatment with naloxone 0.3 mg kg(-1).
      Morphine (0.3-10 mg kg(-1) i.p.) increased threshold pressure but did not
      significantly increase micturition volume in doses not resulting in overflow
      incontinence. 6 (+/-)-Tramadol 10 mg kg(-1) increased urine production, an effect
      blocked by desmopressin 25 ng kg(-1). 7 (+/-)-Tramadol effectively inhibits
      micturition in conscious rats by stimulating micro -opioid receptors. A synergy
      between opioid receptor stimulation and monoamine reuptake inhibition may
      contribute to the micturition effects.

PMID- 12812998
TI  - NADH supplementation decreases pinacidil-primed I K ATP in ventricular
      cardiomyocytes by increasing intracellular ATP.
AB  - 1 The aim of this study was to investigate the effect of nicotinamide-adenine
      dinucleotide (NADH) supplementation on the metabolic condition of isolated guinea
      pig ventricular cardiomyocytes. The pinacidil-primed ATP-dependent potassium
      current I(K(ATP)) was used as an indicator of subsarcolemmal ATP concentration
      and intracellular adenine nucleotide contents were measured. 2 Membrane currents
      were studied using the patch-clamp technique in the whole-cell recording mode at
      36-37 degrees C. Adenine nucleotides were determined by HPLC. 3 Under
      physiological conditions (4.3 mM ATP in the pipette solution, ATP(i)) I(K(ATP))
      did not contribute to basal electrical activity. 4 The ATP-dependent potassium
      (K((ATP))) channel opener pinacidil activated I(K(ATP)) dependent on [ATP](i)
      showing a significantly more pronounced activation at lower (1 mM) [ATP](i). 5
      Supplementation of cardiomyocytes with 300 micro g ml(-1) NADH (4-6 h) resulted
      in a significantly reduced I(K(ATP)) activation by pinacidil compared to control
      cells. The current density was 13.8+/-3.78 (n=6) versus 28.9+/-3.38 pA pF(-1)
      (n=19; P<0.05). 6 Equimolar amounts of the related compounds nicotinamide and
      NAD(+) did not achieve a similar effect like NADH. 7 Measurement of adenine
      nucleotides by HPLC revealed a significant increase in intracellular ATP (NADH
      supplementation: 45.6+/-1.88 nmol mg(-1) protein versus control: 35.4+/-2.57 nmol
      mg(-1) protein, P<0.000005). 8 These data show that supplementation of guinea-pig
      ventricular cardiomyocytes with NADH results in a decreased activation of
      I(K(ATP)) by pinacidil compared to control myocytes, indicating a higher
      subsarcolemmal ATP concentration. 9 Analysis of intracellular adenine nucleotides
      by HPLC confirmed the significant increase in ATP.

PMID- 12812999
TI  - Anticonvulsant activity, teratogenicity and pharmacokinetics of novel
      valproyltaurinamide derivatives in mice.
AB  - 1 The purpose of this study was to synthesize novel valproyltaurine (VTA)
      derivatives including valproyltaurinamide (VTD), N-methyl-valproyltaurinamide (M
      VTD), N,N-dimethyl-valproyltaurinamide (DM-VTD) and N-isopropyl
      valproyltaurinamide (I-VTD) and evaluate their structure-pharmacokinetic
      pharmacodynamic relationships with respect to anticonvulsant activity and
      teratogenic potential. However, their hepatotoxic potential could not be
      evaluated. The metabolism and pharmacokinetics of these derivatives in mice were
      also studied. 2 VTA lacked anticonvulsant activity, but VTD, DM-VTD and I-VTD
      possessed anticonvulsant activity in the Frings audiogenic seizure susceptible
      mice (ED(50) values of 52, 134 and 126 mg kg(-1), respectively). 3 VTA did not
      have any adverse effect on the reproductive outcome in the Swiss Vancouver/Fnn
      mice following a single i.p. injection of 600 mg kg(-1) on gestational day (GD)
      8.5. VTD (600 mg kg(-1) at GD 8.5) produced an increase in embryolethality, but
      unlike valproic acid, it did not induce congenital malformations. DM-VTD and I
      VTD (600 mg kg(-1) at GD 8.5) produced a significant increase in the incidence of
      gross malformations. The incidence of birth defects increased when the length of
      the alkyl substituent or the degree of N-alkylation increased. 4 In mice, N
      alkylated VTDs underwent metabolic N-dealkylation to VTD. DM-VTD was first
      biotransformed to M-VTD and subsequently to VTD. I-VTD's fraction metabolized to
      VTD was 29%. The observed metabolic pathways suggest that active metabolites may
      contribute to the anticonvulsant activity of the N-alkylated VTDs and reactive
      intermediates may be formed during their metabolism. In mice, VTD had five to 10
      times lower clearance (CL), and three times longer half-life than I-VTD and DM
      VTD, making it a more attractive compound than DM-VTD and I-VTD for further
      development. VTD's extent of brain penetration was only half that observed for
      the N-alkylated taurinamides suggesting that it has a higher intrinsic activity
      that DM-VTD and I-VTD. 5 In conclusion, from this series of compounds, although
      VTD caused embryolethality, this compound emerged as the most promising new
      antiepileptic drug, having a preclinical spectrum characterized by the highest
      anticonvulsant potential, lowest potential for teratogenicity and favorable
      pharmacokinetics.

PMID- 12813000
TI  - Prevention of cultured rat stellate cell transformation and endothelin-B receptor
      upregulation by retinoic acid.
AB  - 1 Physiologically, perisinusoidal hepatic stellate cells (HSC) are quiescent and
      store retinoids. During liver injury and in cell culture, HSC transform into
      proliferating myofibroblast-like cells that express alpha-smooth muscle actin
      (alpha-sma) and produce excessive amounts of extracellular matrix. During
      transformation (also known as activation), HSC are depleted of the retinoid
      stores, and their expression of the endothelin-1 (ET-1) system is increased. ET-1
      causes contraction of transformed HSC and is implicated in their proliferation
      and fibrogenic activity. In order to understand the association between
      retinoids, ET-1 and the activation of HSC, we investigated the effect of 13-cis
      retinoic acid on the transformation of cultured HSC and the expression of ET-1
      system. 2 HSC derived from normal rat liver were maintained for 10-12 days in a
      medium supplemented with 5% serum and containing 2.5 micro M retinoic acid
      without or with 50 nM ET-1 (ETA+ETB agonist) or sarafotoxin S6c (ETB agonist). In
      another set of experiments, cells treated for 10-12 days with vehicle (ethanol)
      or retinoic acid were challenged with ET-1 or sarafotoxin S6c, and various
      determinations were made at 24 h. 3 Retinoic acid inhibited transformation and
      proliferation of HSC as assessed by morphological characteristics, expression of
      alpha-sma, bromodeoxyuridine incorporation and cell count. Retinoic acid also
      prevented upregulation of ETB receptors without affecting ET-1 or ETA expression.
      Total protein synthesis ([(3)H]leucine incorporation), collagen alpha types I
      mRNA expression and collagen synthesis ([(3)H]proline incorporation) were lower
      in retinoic acid-treated cells. Although ET-1-treated cells were morphologically
      similar to the control cells, their expression of alpha-smooth muscle actin was
      significantly inhibited. The presence of retinoic acid in the medium during
      treatment with ET-1 caused further reduction in the expression of alpha-smooth
      muscle actin. ET-1 and sarafotoxin S6c stimulated total protein synthesis in
      vehicle- and retinoic acid-treated cells, but collagen synthesis only in the
      latter. 4 These results showing prevention of HSC activation and negative
      regulation of ETB receptor expression in them by retinoic acid may have important
      pathophysiologic implications.

PMID- 12813001
TI  - Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands
      of the cannabinoid-type CB2 receptor.
AB  - 1 Two cannabinoid receptors, CB1 and CB2, have been identified. The CB1 receptor
      is preferentially expressed in brain, and the CB2 receptor in cells of leukocyte
      lineage. We identified the mRNA for the CB1 receptor in human neuroblastoma SH
      SY5Y cells, and the mRNA and protein for the CB2 receptor in human microglia and
      THP-1 cells. 2 Delta(9)-and Delta(8)-tetrahydrocannabinol (THC) were toxic when
      added directly to SH-SY5Y neuroblastoma cells. The toxicity of Delta(9)- THC was
      inhibited by the CB1 receptor antagonist SR141716A but not by the CB2 receptor
      antagonist SR144528. The endogenous ligand anandamide was also toxic, and this
      toxicity was enhanced by inhibitors of its enzymatic hydrolysis. 3 The selective
      CB2 receptor ligands JWH-015 and indomethacin morpholinylamide (BML-190), when
      added to THP-1 cells before stimulation with lipopolysaccharide (LPS) and IFN
      gamma, reduced the toxicity of their culture supernatants to SH-SY5Y cells. JWH
      015 was more effective against neurotoxicity of human microglia than THP-1 cells.
      The antineurotoxic activity of JWH-015 was blocked by the selective CB2 receptor
      antagonist SR144528, but not by the CB1 receptor antagonist SR141716A. This
      activity of JWH-015 was synergistic with that of the 5-lipoxygenase (5-LOX)
      inhibitor REV 5901. 4 Cannabinoids inhibited secretion of IL-1beta and tumor
      necrosis factor-alpha (TNF-alpha) by stimulated THP-1 cells, but these effects
      could not be directly correlated with their antineurotoxic activity. 5 Specific
      CB2 receptor ligands could be useful anti-inflammatory agents, while avoiding the
      neurotoxic and psychoactive effects of CB1 receptor ligands such as Delta(9)-THC.

PMID- 12813002
TI  - Upregulation of cytochromes P450 2B in rat liver by orphenadrine.
AB  - 1 The alkylamine drug orphenadrine (ORPH) is an inducer and inhibitor of the
      microsomal cytochrome P450 (CYP) system in mammals. This study evaluated the
      selectivity of CYP induction by ORPH in rat liver. 2 Immunoblot analysis
      indicated that ORPH was a selective inducer of the phenobarbitone (PB)-inducible
      CYP2B in rat liver. CYP2B protein was increased to approximately 14-fold of
      levels in untreated rat liver. By comparison PB increased CYP2B expression 40
      fold. Corresponding increases in the activity of CYP2B-dependent androstenedione
      16beta-hydroxylation were measured in microsomes from ORPH and PB-induced rats. 3
      Northern analysis indicated that CYP2B1/2 mRNA was increased in ORPH-induced rat
      liver. Consistent with this finding, ORPH was found to activate a PB-responsive
      enhancer module in constitutive androstane receptor (CAR)-transfected Hep G2
      cells. 4 Other alkylamines like troleandomycin impair CYP turnover. We tested
      whether ORPH induction of CYP2B may include a post-translational component. In PB
      pretreated animals ORPH administration delayed the loss of CYP2B after PB
      withdrawal, but no evidence for altered turnover was found. 5 These studies
      establish ORPH as a selective inducer of CYP2B in rat liver. Induction appears to
      be mediated pretranslationally by CAR activation of CYP2B gene transcription.
      Post-translational stabilisation by an ORPH metabolite does not elicit induction.
      Induction of CYP2B may influence pharmacokinetic interactions involving ORPH.

PMID- 12813003
TI  - Reactive oxygen species induce swelling and cytochrome c release but not
      transmembrane depolarization in isolated rat brain mitochondria.
AB  - 1 In this study, we have used isolated brain mitochondria to investigate the
      effects of superoxide anions (O(2)(-)) on mitochondrial parameters related to
      apoptosis, such as swelling, potential, enzymatic activity, NAD(P)H, cytochrome c
      release, and caspase activity. 2 Addition of the reactive oxygen species (ROS)
      generator KO(2) produced brain mitochondrial swelling, which was blocked by
      cyclosporin A (CSA), and which was Ca(2+) independent. 3 Calcium induced
      mitochondrial swelling only at high concentrations and in the presence of
      succinate. This correlated with the increase in O(2)(-) production detected with
      hydroethidine in mitochondrial preparations exposed to Ca(2+) and the fact that
      ROS were required for Ca(2+)-induced mitochondrial swelling. 4 Superoxide anions,
      but not Ca(2+), decreased citrate synthase and dehydrogenase enzymatic activities
      and dropped total mitochondrial NAD(P)H levels. 5 Calcium, but not O(2)(-),
      triggered a rapid loss of mitochondrial potential. Calcium-induced Deltapsi(m)
      dissipation was inhibited by Ruthenium Red, but not by CSA. 6 Calcium- and
      superoxide-induced mitochondrial swelling released cytochrome c and increased
      caspase activity from isolated mitochondria in a CS A-sensitive manner. 7 In
      summary, superoxide potently triggers mitochondrial swelling and the release of
      proteins involved in activation of postmitochondrial apoptotic pathways in the
      absence of mitochondrial depolarization.

PMID- 12813004
TI  - Endocannabinoids protect the rat isolated heart against ischaemia.
AB  - 1 The purpose of this study was to determine whether endocannabinoids can protect
      the heart against ischaemia and reperfusion. 2 Rat isolated hearts were exposed
      to low-flow ischaemia (0.5-0.6 ml min(-1)) and reperfusion. Functional recovery
      as well as CK and LDH overflow into the coronary effluent were monitored. Infarct
      size was determined at the end of the experiments. Phosphorylation levels of p38,
      ERK1/2, and JNK/SAPK kinases were measured by Western blots. 3 None of the
      untreated hearts recovered from ischaemia during the reperfusion period.
      Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2
      arachidonoylglycerol (2-AG), but not anandamide (up to 1 micro M), 15 min before
      and throughout the ischaemic period, improved myocardial recovery and decreased
      the levels of coronary CK and LDH. PEA and 2-AG also reduced infarct size. 4 The
      CB(2)-receptor antagonist, SR144528, blocked completely the cardioprotective
      effect of both PEA and 2-AG, whereas the CB(1)-receptor antagonist, SR141716A,
      blocked partially the effect of 2-AG only. In contrast, both ACEA and JWH015, two
      selective agonists for CB(1)- and CB(2)- receptors, respectively, reduced infarct
      size at a concentration of 50 nM. 5 PEA enhanced the phosphorylation level of p38
      MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation
      level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective
      effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580,
      and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC
      inhibitor, chelerythrine. 6 In conclusion, endocannabinoids exert a strong
      cardioprotective effect in a rat model of ischaemia-reperfusion that is mediated
      mainly through CB(2)-receptors, and involves p38, ERK1/2, as well as PKC
      activation.

PMID- 12813005
TI  - Peroxidation of docosahexaenoic acid is responsible for its effects on I TO and I
      SS in rat ventricular myocytes.
AB  - 1 Exposure to docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty
      acid, is known to block several ionic currents such as the transient outward
      current I(TO). It has also been reported to activate certain potassium channels.
      It has been suggested that these effects, observed in single-cell experiments,
      participate in the antiarrhythmic properties of these compounds in vivo. 2 DHA is
      highly prone to peroxidation. To investigate the influence peroxidation may have
      on the effects of DHA on ion channels, we studied I(TO) and the steady-state
      outward current I(SS) in isolated rat ventricular myocytes under ruptured whole
      cell patch-clamp conditions. 3 A measure of 10 micro M DHA alone reduced I(TO),
      evoked by a pulse to +70 mV, by 74.8+/-10.8% (n=7) and activated a delayed
      outward current with kinetic properties different from I(SS). 4 When an
      antioxidant, alpha-tocopherol (1 micro M), was added together with DHA, the
      blockade of I(TO) was reduced to 38.5+/-7.7% (n=8) and the delayed outward
      current was not activated. alpha-Tocopherol alone had no effect on these
      currents. 5 When an oxidant, hydrogen peroxide (1 micro M), was applied together
      with DHA, the blockade of I(TO) was almost complete (98.4+/-1.0%, n=7) and a
      large delayed outward current was activated. A measure of 1 micro M hydrogen
      peroxide alone had no effect on these currents. 6 Measurements of nonperoxidized
      DHA in experimental solutions confirmed the negative relation between DHA
      concentration and the effects on the currents. 7 We conclude that rather than DHA
      itself, it is the peroxidation products of DHA that block I(TO) and activate a
      delayed outward current in in vitro single-cell experiments. These findings have
      important implications for the extrapolation of in vitro experimental findings to
      the antiarrhythmic effects of DHA in vivo because, in vivo, peroxidation of DHA
      is unlikely to occur.

PMID- 12813006
TI  - Retinoids as a potential treatment for experimental puromycin-induced nephrosis.
AB  - 1 Puromycin aminonucleoside (PAN)-induced nephrosis is a model of human minimal
      change disease. In rats, PAN induces nephrotic-range proteinuria, renal
      epithelial cell (podocyte) damage, infiltration of mononuclear leukocytes, and
      apoptosis of several renal cell types. 2 Retinoic acid (RA) modulates a wide
      range of biological processes, such as inflammation and apoptosis. Since renal
      damage by PAN is characterized by inflammatory infiltration and epithelial cell
      death, the effect of treatment with all-trans RA (tRA) was examined in the PAN
      nephrosis model and in the cultured differentiated podocyte. 3 Treatment with tRA
      4 days after PAN injection did not inhibit the proteinuria peak but reversed it
      significantly. However, treatment with tRA both before and 2 days after the
      injection of PAN protected the glomerular epithelial cells, diminishing the
      cellular edema and diffuseness of the foot process effacement. Preservation of
      the podocyte architecture correlated with the inhibition of proteinuria. The anti
      inflammatory effect of tRA was evidenced by the inhibition of PAN-induced
      interstitial mononuclear cell infiltration and the decreased renal expression of
      two molecules involved in monocyte infiltration: fibronectin and monocyte
      chemoattractant protein-1. TUNEL assays showed that tRA inhibited the PAN-induced
      apoptosis of cultured differentiated mouse podocytes. 4 We conclude that tRA
      treatment may prevent proteinuria by protecting the podocytes from injury and
      diminishing the interstitial mononuclear infiltrate in the model of PAN
      nephrosis. Retinoids are a potential new treatment for kidney diseases
      characterized by proteinuria and mononuclear cell infiltration.

PMID- 12813007
TI  - Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan
      krait (Bungarus candidus).
AB  - 1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan
      krait Bungarus candidus, belongs to the poorly characterized subfamily of
      nonconventional three-finger toxins present in Elapid venoms. The current study
      details the pharmacological effects of candoxin at the neuromuscular junction. 2
      Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve
      muscle preparations and the tibialis anterior muscle of anaesthetized rats. In
      contrast to the virtually irreversible postsynaptic neuromuscular blockade
      produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced
      by candoxin was rapidly and completely reversed by washing or by the addition of
      the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of
      four fade during the onset of and recovery from neuromuscular blockade, both, in
      vitro and in vivo. The fade phenomenon has been attributed to a blockade of
      putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a
      positive feedback mechanism and maintain adequate transmitter release during
      rapid repetitive stimulation. In this respect, candoxin closely resembles the
      neuromuscular blocking effects of d-tubocurarine, and differs markedly from
      curaremimetic alpha-neurotoxins that produce little or no fade. 4
      Electrophysiological experiments confirmed that candoxin produced a readily
      reversible blockade (IC(50) approximately 10 nM) of oocyte-expressed muscle
      (alphabetagammadelta) nAChRs. Like alpha-conotoxin MI, well known for its
      preferential binding to the alpha/delta interface of the muscle
      (alphabetagammadelta) nAChR, candoxin also demonstrated a biphasic concentration
      response inhibition curve with a high- (IC(50) approximately 2.2 nM) and a low-
      (IC(50) approximately 98 nM) affinity component, suggesting that it may exhibit
      differential affinities for the two binding sites on the muscle
      (alphabetagammadelta) receptor. In contrast, curaremimetic alpha-neurotoxins have
      been reported to antagonize both binding sites with equal affinity.

PMID- 12813008
TI  - Effects of heparin and related molecules upon neutrophil aggregation and elastase
      release in vitro.
AB  - 1 Neutrophil-derived elastase is an enzyme implicated in the pathogenesis of
      chronic obstructive pulmonary disease (COPD). Heparin inhibits the enzymatic
      activity of elastase and here we provide evidence for the first time that heparin
      can inhibit the release of elastase from human neutrophils. 2 Unfractionated and
      low molecular weight heparins (UH and LMWH, 0.01-1000 U ml(-1)) and corresponding
      concentrations (0.06-6000 micro g ml(-1)) of nonanticoagulant O-desulphated
      heparin (ODH), dextran sulphate (DS) and nonsulphated poly-L-glutamic acid (PGA)
      were compared for their effects on both elastase release from and aggregation of
      neutrophils. 3 UH, ODH and LMWH inhibited (P<0.05) the homotypic aggregation of
      neutrophils, in response to both N-formyl-methionyl-leucyl-phenylalanine (fMLP,
      10(-6) M) and platelet-activating factor (PAF, 10(-6) M), as well as elastase
      release in response to these stimuli, in the absence and presence of the priming
      agent tumour necrosis factor-alpha (TNF-alpha, 100 U ml(-1)). 4 DS inhibited
      elastase release under all the conditions of cellular activation tested (P<0.05)
      but had no effect on aggregation. PGA lacked efficacy in either assay, suggesting
      general sulphation to be important in both effects of heparin on neutrophil
      function and specific patterns of sulphation to be required for inhibition of
      aggregation. 5 Further investigation of the structural requirements for
      inhibition of elastase release confirmed the nonsulphated GAG hyaluronic acid and
      neutral dextran, respectively, to be without effect, whereas the IP(3) receptor
      antagonist 2-aminoethoxydiphenylborate (2-APB) mimicked the effects of heparin,
      itself an established IP(3) receptor antagonist, suggesting this to be a possible
      mechanism of action.

PMID- 12813009
TI  - Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor
      mediated relaxation of human penile resistance arteries.
AB  - 1 We have evaluated the participation of endothelium-derived hyperpolarizing
      factor (EDHF) in the endothelium-dependent relaxation of isolated human penile
      resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition,
      the effect of the angioprotective agent, calcium dobesilate (DOBE), on the
      endothelium-dependent relaxation of these tissues was investigated. 2 Combined
      inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly
      abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC,
      while 60% relaxation of HPRA was observed under these conditions. Endothelium
      dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by
      raising the extracellular concentration of K(+) (35 mM) or by blocking Ca(2)(+)
      activated K(+) channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100
      nM), suggesting the involvement of EDHF in these responses. 3 Endothelium
      dependent relaxation to ACh was markedly enhanced by DOBE (10 micro M) in HPRA
      but not in HCC. The potentiating effects of DOBE on ACh-induced responses in
      HPRA, remained after NOS and COX inhibition, were reduced by inhibition of
      cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high
      K(+) or a combination of APA and CTX. 4 In vivo, DOBE (10 mg kg(-1) i.v.)
      significantly potentiated the erectile responses to cavernosal nerve stimulation
      in male rats. 5 EDHF plays an important role in the endothelium-dependent
      relaxation of HPRA but not in HCC. DOBE significantly improves endothelium
      dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses
      in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of
      erectile dysfunction (ED) and DOBE could be considered a candidate for oral
      therapy for ED.

PMID- 12813010
TI  - Functional consequences of neuropeptide Y Y 2 receptor knockout and Y2 antagonism
      in mouse and human colonic tissues.
AB  - 1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP)
      differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and
      human isolated colon. 2 The aim of this study was to characterise Y(2) receptor
      mediated responses in colon mucosa and longitudinal smooth muscle preparations
      from wild type (Y(2)+/+) and knockout (Y(2)-/-) mice and to compare the former
      with human mucosal Y agonist responses. Inhibition of mucosal short-circuit
      current and increases in muscle tone were monitored in colonic tissues from
      Y(2)+/+ and Y(2)-/- mice+/-Y(1) ((R)-N-[[4
      (aminocarbonylaminomethyl)phenyl)methyl]-N(2)-(diphenylacetyl)-argininamide
      trifluoroacetate (BIBO3304) or Y(2) (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)
      oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2
      [1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide
      (BIIE0246) antagonists. 3 Predictably, Y(2)-/- tissues were insensitive to Y(2)
      preferred agonist PYY(3-36) (</=100 nM), but unexpectedly Y(4)-preferred PP
      responses were right-shifted probably as a consequence of elevated circulating PP
      levels, particularly in male Y(2)-/- mice (Sainsbury et al., 2002). 4 BIBO3304
      and BIIE0246 elevated mucosal ion transport, indicating blockade of inhibitory
      mucosal tone in Y(2)+/+ tissue. While BIBO3304 effects were unchanged, those to
      BIIE0246 were absent in Y(2)-/- mucosae. Neither antagonist altered muscle tone;
      however, BIIE0246 blocked NPY and PYY(3-36) increases in Y(2)+/+ basal tone.
      BIBO3304 abolished residual Y(1)-mediated NPY responses in Y(2)-/- smooth muscle.
      5 Tetrodotoxin significantly reduced BIIE0246 and PYY(3-36) effects in Y(2)+/+
      mouse and human mucosae, but had no effect upon Y-agonist contractile responses,
      indicating that Y(2) receptors are located on submucosal, but not myenteric
      neurones. 6 Tonic activation of submucosal Y(2) receptors by endogenous NPY, PYY
      or PYY(3-36) could indirectly reduce mucosal ion transport in murine and human
      colon, while direct activation of Y(2) receptors on longitudinal muscle results
      in contraction.

PMID- 12813011
TI  - Selective activation by photodynamic action of cholecystokinin receptor in the
      freshly isolated rat pancreatic acini.
AB  - 1 Sulphonated aluminium phthalocyanine (SALPC) photodynamic action induces
      amylase secretion and permanent calcium oscillation in rat pancreatic acinar
      cells, because of the activation of phospholipase C or signalling proteins
      upstream. The aim of the present study was to investigate the involvement of
      muscarinic acetylcholine and cholecystokinin (CCK) receptors. 2 Muscarinic
      receptor antagonist atropine (10 micro M) blocked amylase secretion induced by
      bethanechol (100 micro M), and CCK(1) receptor antagonist (S)-N-[1-(2
      fluorophenyl)-3,4,6,7-tetrahydor-4-oxo-pyrrolo-[3,2,1-jk][1,4] benzodiazepine
      3yl]-1H-indole-2-carboxamide (FK480) (1 micro M) blocked amylase secretion
      induced by CCK (100 pM). 3 Amylase secretion induced by SALPC photodynamic action
      was not inhibited when atropine and FK480 were present during photodynamic
      action. However, addition of FK480 1 micro M after initiation of photodynamic
      action inhibited photodynamic amylase secretion. Bethanechol (10, 100 micro M)
      added after photodynamic action resulted in a full secretory response. 4 Atropine
      (10 nM) abolished calcium oscillation induced by bethanechol (5 micro M), and
      FK480 (10 nM) blocked calcium oscillation induced by CCK (10 pM). 5 Atropine up
      to 10 micro M was without effect on Ca(2+) oscillation triggered by photodynamic
      action, but these oscillations were abolished by FK480 (10 nM). FK480 (10 nM) had
      no effect on calcium oscillations induced by bethanechol (5 micro M). Bethanechol
      5 micro M, added after FK480 blockade of photodynamic calcium oscillation, still
      triggered regular calcium oscillation. 6 It is concluded that SALPC photodynamic
      action selectively and permanently activates CCK receptor in rat pancreatic
      acini. Such permanent and selective modulation of signalling proteins has
      important implications for the treatment of pancreatitis, prion diseases, and
      neurodegenerative disorders.

PMID- 12813012
TI  - Monogenic hypercholesterolemia: new insights in pathogenesis and treatment.

PMID- 12813013
TI  - C-reactive protein: a critical update.

PMID- 12813014
TI  - AIP1: a new player in TNF signaling.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is an upstream activator of JNK and
      p38 MAPK signaling cascades. Evidence now shows that the ASK1-interacting
      protein, AIP1, plays an important role in TNF-alpha-induced ASK1 activation by
      facilitating dissociation from its inhibitor.

PMID- 12813015
TI  - Arginase: marker, effector, or candidate gene for asthma?
AB  - Microarray analysis of the expression profiles of lung tissue in two murine
      models of asthma revealed high levels of arginase I and arginase II activity, in
      association with IL-4 and IL-13 overexpression, suggesting that arginine pathways
      are critical in the pathogenesis of asthma.

PMID- 12813016
TI  - An eye on insulin.
AB  - Diabetic retinopathy, the most frequent complication of diabetes and leading
      cause of vision loss, involves vascular and neural damage in the retina. Insulin
      and IGF-1 signaling are now shown to contribute to retinal neovascularization, in
      part, by modulating the expression of various vascular mediators.

PMID- 12813017
TI  - Tolerance: of mice and men.
AB  - Little is known about the effect of an individual's immune history on his or her
      response to an allogeneic tissue transplant. An important study now reveals that
      individuals harboring virally-induced memory T cells that are cross reactive with
      donor alloantigen are resistant to conventional strategies designed to induce
      transplant tolerance.

PMID- 12813018
TI  - Utilization of sialic acid as a coreceptor is required for reovirus-induced
      biliary disease.
AB  - Infection of neonatal mice with some reovirus strains produces a disease similar
      to infantile biliary atresia, but previous attempts to correlate reovirus
      infection with this disease have yielded conflicting results. We used isogenic
      reovirus strains T3SA- and T3SA+, which differ solely in the capacity to bind
      sialic acid as a coreceptor, to define the role of sialic acid in reovirus
      encephalitis and biliary tract infection in mice. Growth in the intestine was
      equivalent for both strains following peroral inoculation. However, T3SA+ spread
      more rapidly from the intestine to distant sites and replicated to higher titers
      in spleen, liver, and brain. Strikingly, mice infected with T3SA+ but not T3SA-
      developed steatorrhea and bilirubinemia. Liver tissue from mice infected with
      T3SA+ demonstrated intense inflammation focused at intrahepatic bile ducts,
      pathology analogous to that found in biliary atresia in humans, and high levels
      of T3SA+ antigen in bile duct epithelial cells. T3SA+ bound 100-fold more
      efficiently than T3SA- to human cholangiocarcinoma cells. These observations
      suggest that the carbohydrate-binding specificity of a virus can dramatically
      alter disease in the host and highlight the need for epidemiologic studies
      focusing on infection by sialic acid-binding reovirus strains as a possible
      contributor to the pathogenesis of neonatal biliary atresia.

PMID- 12813019
TI  - Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects
      against retinal neovascularization.
AB  - Both insulin and IGF-1 have been implicated in control of retinal endothelial
      cell growth, neovascularization, and diabetic retinopathy. To precisely define
      the role of insulin and IGF-1 signaling in endothelium in these processes, we
      have used the oxygen-induced retinopathy model to study mice with a vascular
      endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1
      receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57%
      decrease in retinal neovascularization as compared with controls. This is
      associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast,
      VENIFARKO mice show only a 34% reduction in neovascularization and a very modest
      reduction in mediator generation. These data indicate that both insulin and IGF-1
      signaling in endothelium play a role in retinal neovascularization through the
      expression of vascular mediators, with the effect of insulin being most important
      in this process.

PMID- 12813020
TI  - VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral
      ischemia.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic protein with
      therapeutic potential in ischemic disorders, including stroke. VEGF confers
      neuroprotection and promotes neurogenesis and cerebral angiogenesis, but the
      manner in which these effects may interact in the ischemic brain is poorly
      understood. We produced focal cerebral ischemia by middle cerebral artery
      occlusion for 90 minutes in the adult rat brain and measured infarct size,
      neurological function, BrdU labeling of neuroproliferative zones, and vWF
      immunoreactive vascular profiles, without and with intracerebroventricular
      administration of VEGF on days 1-3 of reperfusion. VEGF reduced infarct size,
      improved neurological performance, enhanced the delayed survival of newborn
      neurons in the dentate gyrus and subventricular zone, and stimulated angiogenesis
      in the striatal ischemic penumbra, but not the dentate gyrus. We conclude that in
      the ischemic brain VEGF exerts an acute neuroprotective effect, as well as longer
      latency effects on survival of new neurons and on angiogenesis, and that these
      effects appear to operate independently. VEGF may, therefore, improve
      histological and functional outcome from stroke through multiple mechanisms.

PMID- 12813021
TI  - Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic
      skeletal muscles.
AB  - Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor
      neurotransmitter, stimulates endothelial cell migration, proliferation, and
      differentiation in vitro. Here, we report on NPY's actions, receptors, and
      mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates
      sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY
      Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY
      at physiological concentrations also induces Y5 receptor, stimulates
      neovascularization, and restores ischemic muscle blood flow and performance. NPY
      mediated ischemic angiogenesis is not prevented by a selective Y1 receptor
      antagonist but is reduced in Y2(-/-) mice. Nonischemic muscle vascularity is also
      lower in Y2(-/-) mice, whereas it is increased in NPY-overexpressing rats
      compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is
      markedly reduced in Y2(-/-) aortas and spontaneous sprouting is severely impaired
      in NPY(-/-) mice. NPY-mediated aortic sprouting, but not cell
      migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and
      abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic
      angiogenesis at physiological concentrations by activating Y2/Y5 receptors and
      eNOS, in part due to release of VEGF. NPY's effectiveness in revascularization
      and restoring function of ischemic tissue suggests its therapeutic potential in
      ischemic conditions.

PMID- 12813022
TI  - Dissection of experimental asthma with DNA microarray analysis identifies
      arginase in asthma pathogenesis.
AB  - Asthma is on the rise despite intense, ongoing research underscoring the need for
      new scientific inquiry. In an effort to provide unbiased insight into disease
      pathogenesis, we took an approach involving expression profiling of lung tissue
      from mice with experimental asthma. Employing asthma models induced by different
      allergens and protocols, we identified 6.5% of the tested genome whose expression
      was altered in an asthmatic lung. Notably, two phenotypically similar models of
      experimental asthma were shown to have distinct transcript profiles. Genes
      related to metabolism of basic amino acids, specifically the cationic amino acid
      transporter 2, arginase I, and arginase II, were particularly prominent among the
      asthma signature genes. In situ hybridization demonstrated marked staining of
      arginase I, predominantly in submucosal inflammatory lesions. Arginase activity
      was increased in allergen-challenged lungs, as demonstrated by increased enzyme
      activity, and increased levels of putrescine, a downstream product. Lung arginase
      activity and mRNA expression were strongly induced by IL-4 and IL-13, and were
      differentially dependent on signal transducer and activator of transcription 6.
      Analysis of patients with asthma supported the importance of this pathway in
      human disease. Based on the ability of arginase to regulate generation of NO,
      polyamines, and collagen, these results provide a basis for pharmacologically
      targeting arginine metabolism in allergic disorders.

PMID- 12813023
TI  - Complement receptor 2-mediated targeting of complement inhibitors to sites of
      complement activation.
AB  - In a strategy to specifically target complement inhibitors to sites of complement
      activation and disease, recombinant fusion proteins consisting of a complement
      inhibitor linked to a C3 binding region of complement receptor (CR) 2 were
      prepared and characterized. Natural ligands for CR2 are C3 breakdown products
      deposited at sites of complement activation. Fusion proteins were prepared
      consisting of a human CR2 fragment linked to either the N terminus or C terminus
      of soluble forms of the membrane complement inhibitors decay accelerating factor
      (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells,
      and all were significantly more effective (up to 20-fold) than corresponding
      untargeted inhibitors at protecting target cells from complement. CR2 fusion
      proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized
      erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2
      fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of
      leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting
      strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF,
      targets to the kidney in mouse models of lupus nephritis that are associated with
      renal complement deposition.

PMID- 12813025
TI  - The thyrotropin receptor autoantigen in Graves disease is the culprit as well as
      the victim.
AB  - Graves disease, a common organ-specific autoimmune disease affecting humans,
      differs from all other autoimmune diseases in being associated with target organ
      hyperfunction rather than organ damage. Clinical thyrotoxicosis is directly
      caused by autoantibodies that activate the thyrotropin receptor (TSHR). The
      etiology of Graves disease is multifactorial, with nongenetic factors playing an
      important role. Of the latter, there is the intriguing possibility that the
      molecular structure of the target antigen contributes to the development of
      thyroid-stimulatory autoantibodies (TSAb's). Among the glycoprotein hormone
      receptors, only the TSHR undergoes intramolecular cleavage into disulfide-linked
      subunits with consequent shedding of some of the extracellular, autoantibody
      binding A subunits. Functional autoantibodies do not arise to the noncleaving
      glycoprotein hormone receptors. Recently, TSAb's were found to preferentially
      recognize shed, rather than attached, A subunits. Here we use a new adenovirus
      mediated animal model of Graves disease to show that goiter and hyperthyroidism
      occur to a much greater extent when the adenovirus expresses the free A subunit
      as opposed to a genetically modified TSHR that cleaves minimally into subunits.
      These data show that shed A subunits induce or amplify the immune response
      leading to hyperthyroidism and provide new insight into the etiology of Graves
      disease.

PMID- 12813024
TI  - Heterologous immunity provides a potent barrier to transplantation tolerance.
AB  - Many strategies have been proposed to induce tolerance to transplanted tissue in
      rodents; however, few if any have shown equal efficacy when tested in nonhuman
      primate transplant models. We hypothesized that a critical distinction between
      specific pathogen-free mice and nonhuman primates or human patients is their
      acquired immune history. Here, we show that a heterologous immune response-
      specifically, virally induced alloreactive memory--is a potent barrier to
      tolerance induction. A critical threshold of memory T cells is needed to promote
      rejection, and CD8(+) "central" memory T cells are primarily responsible.
      Finally, treatment with deoxyspergualin, an inhibitor of NF-kappa B
      translocation, together with costimulation blockade, synergistically impairs
      memory T cell activation and promotes antigen-specific tolerance of memory. These
      data offer a potential explanation for the difficulty encountered when inducing
      tolerance in nonhuman primates and human patients and provide insight into the
      signaling pathways essential for memory T cell activation and function.

PMID- 12813026
TI  - Rheumatic fever-associated Streptococcus pyogenes isolates aggregate collagen.
AB  - Acute rheumatic fever is a serious autoimmune sequel of Streptococcus pyogenes
      infection. This study shows that serotype M3 and M18 S. pyogenes isolated during
      outbreaks of rheumatic fever have the unique capability to bind and aggregate
      human basement membrane collagen type IV. M3 protein is identified as collagen
      binding factor of M3 streptococci, whereas M18 isolates bind collagen through a
      hyaluronic acid capsule, revealing a novel function for M3 protein and capsule.
      Following in vivo mouse passage, conversion of a nonencapsulated and collagen
      binding negative M1 S. pyogenes into an encapsulated, collagen-binding strain
      further supports the crucial role of capsule in mediating collagen binding.
      Collagen binding represents a novel colonization mechanism, as it is demonstrated
      that S. pyogenes bind to collagen matrix in vitro and in vivo. Moreover,
      immunization of mice with purified recombinant M3 protein led to the generation
      of anti-collagen type IV antibodies. Finally, sera from acute rheumatic fever
      patients had significantly increased titers of anti-collagen type IV antibodies
      as compared with healthy controls. These findings may suggest a link between the
      potential of rheumatogenic S. pyogenes isolates to bind collagen, and the
      presence of collagen-reactive autoantibodies in the serum of rheumatic fever
      patients, which may form a basis for post-streptococcal rheumatic disease. These
      anti-collagen antibodies may form a basis for poststreptococcal rheumatic
      disease.

PMID- 12813027
TI  - Site-specific somatic mitochondrial DNA point mutations in patients with
      thymidine phosphorylase deficiency.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder caused by loss-of-function mutations in the gene encoding
      thymidine phosphorylase (TP). This deficiency of TP leads to increased
      circulating levels of thymidine (deoxythymidine, dThd) and deoxyuridine (dUrd)
      and has been associated with multiple deletions and depletion of mitochondrial
      DNA (mtDNA). Here we describe 36 point mutations in mtDNA of tissues and cultured
      cells from MNGIE patients. Thirty-one mtDNA point mutations (86%) were T-to-C
      transitions, and of these, 25 were preceded by 5'-AA sequences. In addition, we
      identified a single base-pair mtDNA deletion and a TT-to-AA mutation. Next
      nucleotide effects and dislocation mutagenesis may contribute to the formation of
      these mutations. These results provide the first demonstration that alterations
      of nucleoside metabolism can induce multiple sequence-specific point mutations in
      humans. We hypothesize that, in patients with TP deficiency, increased levels of
      dThd and dUrd cause mitochondrial nucleotide pool imbalances, which, in turn,
      lead to mtDNA abnormalities including site-specific point mutations.

PMID- 12813028
TI  - Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10
      in the epidermis.
AB  - IL-10 is a pleiotropic cytokine that inhibits several immune parameters,
      including Th1 cell-mediated immune responses, antigen presentation, and antigen
      specific T cell proliferation. Recent data implicate IL-10 as a mediator of
      suppression of cell-mediated immunity induced by exposure to UVB radiation (280
      320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we
      engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the
      epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+)
      epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional
      lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression
      by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated
      a smaller delayed-type hypersensitivity response to allogeneic cells upon
      challenge but had normal contact hypersensitivity to an epicutaneously applied
      hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased
      ability to stimulate allogeneic T cell proliferation, as did splenocytes.
      Additionally, chronic exposure of mice to UVB radiation led to the development of
      fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice
      had increased splenic NK cell activity against YAC-1targets. These findings
      support the concept that IL-10 is an important regulator of cutaneous immune
      function.

PMID- 12813029
TI  - AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of
      ASK1 from its inhibitor 14-3-3.
AB  - TNF-alpha activates ASK1 in part by dissociating 14-3-3 from apoptosis signal
      regulating kinase 1 (ASK1). In the present study, we identified a novel Ras
      GTPase-activating protein (Ras-GAP) as an ASK1-interacting protein (AIP1). AIP1
      binds to the C-terminal domain of ASK1 via a lysine-rich cluster within the N
      terminal C2 domain. AIP1 exists in a closed form through an intramolecular
      interaction between the N-terminus and the C-terminus, and TNF-alpha induces
      unfolding of AIP1 leading to association of AIP1 with ASK1. Thus, the N-terminus
      of AIP1 containing the C2 and GAP domains constitutively binds to ASK1 and
      facilitates the release of 14-3-3 from ASK1. In contrast to 14-3-3, AIP1 binds
      preferentially to dephosphorylated ASK1. Recruited AIP1 enhances ASK1-induced JNK
      activation, and the ASK1 binding and the GAP activity of AIP1 are critical for
      AIP1-enhanced ASK1 activation. Furthermore, TNF-induced ASK1/JNK activation is
      significantly blunted in cells where AIP1 is knocked down by RNA interference.
      These data suggest that AIP1 mediates TNF-alpha-induced ASK1 activation by
      facilitating dissociation of inhibitor 14-3-3 from ASK1, a novel mechanism by
      which TNF-alpha activates ASK1.

PMID- 12813030
TI  - Polyubiquitin serves as a recognition signal, rather than a ratcheting molecule,
      during retrotranslocation of proteins across the endoplasmic reticulum membrane.
AB  - Polyubiquitination is required for retrotranslocation of proteins from the
      endoplasmic reticulum back into the cytosol, where they are degraded by the
      proteasome. We have tested whether the release of a polypeptide chain into the
      cytosol is caused by a ratcheting mechanism in which the attachment of
      polyubiquitin prevents the chain from moving back into the endoplasmic reticulum.
      Using a permeabilized cell system in which major histocompatibility complex class
      I heavy chains are retrotranslocated under the influence of the human
      cytomegalovirus protein US11, we demonstrate that polyubiquitination alone is
      insufficient to provide the driving force for retrotranslocation. Substrate
      release into the cytosol requires an additional ATP-dependent step. Release
      requires a lysine 48 linkage of ubiquitin chains. It does not occur when
      polyubiquitination of the substrate is carried out with glutathione S-transferase
      (GST)-ubiquitin, and this correlates with poly-GST-ubiquitin not being recognized
      by a ubiquitin-binding domain in the Ufd1-Npl4 cofactor of the ATPase p97. These
      data suggest that polyubiquitin does not serve as a ratcheting molecule. Rather,
      it may serve as a recognition signal for the p97-Ufd1-Npl4 complex, a component
      implicated in the movement of substrate into the cytosol.

PMID- 12813031
TI  - Analysis of p53 "latency" and "activation" by fluorescence correlation
      spectroscopy. Evidence for different modes of high affinity DNA binding.
AB  - The concept that the tumor suppressor p53 is a latent DNA-binding protein that
      must become activated for sequence-specific DNA binding recently has been
      challenged, although the "activation" phenomenon has been well established in in
      vitro DNA binding assays. Using electrophoretic mobility shift assays and
      fluorescence correlation spectroscopy, we analyzed the binding of "latent" and
      "activated" p53 to double-stranded DNA oligonucleotides containing or not
      containing a p53 consensus binding site (DNAspec or DNAunspec, respectively). In
      the absence of competitor DNA, latent p53 bound DNAspec and DNAunspec with high
      affinity in a sequence-independent manner. Activation of p53 by the addition of
      the C-terminal antibody PAb421 significantly decreased the binding affinity for
      DNAunspec and concomitantly increased the binding affinity for DNAspec. The net
      result of this dual effect is a significant difference in the affinity of
      activated p53 for DNAspec and DNAunspec, which explains the activation of p53.
      High affinity nonspecific DNA binding of latent p53 required both the p53 core
      domain and the p53 C terminus, whereas high affinity sequence-specific DNA
      binding of activated p53 was mediated by the p53 core domain alone. The data
      suggest that high affinity nonspecific DNA binding of latent and high affinity
      sequence-specific binding of activated p53 to double-stranded DNA differ in their
      requirement for the C terminus and involve different structural features of the
      core domain. Because high affinity nonspecific DNA binding of latent p53 is
      restricted to wild type p53, we propose that it relates to its tumor suppressor
      functions.

PMID- 12813032
TI  - Crystal structure of monomeric actin in the ATP state. Structural basis of
      nucleotide-dependent actin dynamics.
AB  - A nucleotide-dependent conformational change regulates actin filament dynamics.
      Yet, the structural basis of this mechanism remains controversial. The x-ray
      crystal structure of tetramethylrhodamine-5-maleimide-actin with bound AMPPNP, a
      non-hydrolyzable ATP analog, was determined to 1.85-A resolution. A comparison of
      this structure to that of tetramethylrhodamine-5-maleimide-actin with bound ADP,
      determined previously under similar conditions, reveals how the release of the
      nucleotide gamma-phosphate sets in motion a sequence of events leading to a
      conformational change in subdomain 2. The side chain of Ser-14 in the catalytic
      site rotates upon Pi release, triggering the rearrangement of the loop containing
      the methylated His-73, referred to as the sensor loop. This in turn causes a
      transition in the DNase I-binding loop in subdomain 2 from a disordered loop in
      ATP-actin to an ordered alpha-helix in ADP-actin. Despite this conformational
      change, the nucleotide cleft remains closed in ADP-actin, similar to ATP-actin.
      An analysis of the existing structures of members of the actin superfamily
      suggests that the cleft is open in the nucleotide-free state.

PMID- 12813033
TI  - The invasive phenotype of Shigella flexneri directs a distinct gene expression
      pattern in the human intestinal epithelial cell line Caco-2.
AB  - Invasion of the human colonic epithelium by Shigella flexneri causes inflammation
      that disrupts the intestinal barrier. Invaded intestinal epithelial cells are the
      major source of mediators recruiting the inflammatory infiltrate. To better
      characterize the global response of intestinal epithelial cells to Shigella
      invasion, Caco-2 cells were infected by an invasive isolate of S. flexneri 5a,
      and their transcriptome was analyzed by Affymetrix (Santa Clara, CA) microarrays
      (12,000 genes) and compared with these elicited by a non-invasive Shigella mutant
      and tumor necrosis factor (TNF)-alpha. The invasive and non-invasive strains
      enhanced transcription of a common pattern of 240 genes, among which genes
      encoding isoforms of cytochrome P-450 were induced. These genes were not induced
      by TNF-alpha. Conversely, both the invasive strain and TNF-alpha induced a common
      set of 18 genes, mainly encoding proinflammatory molecules. They also induced
      specific sets of genes. The transcriptome induced by the invasive strain was
      characterized by the induction of early genes (i.e. expressed within the first 45
      min of invasion) and late genes (i.e. after 60 min of invasion) whose pattern was
      strongly biased toward stimulation of granulopoiesis, chemoattraction,
      activation, and adherence of polymorphonuclear leukocytes. When compared with a
      non-invasive Shigella and TNF-alpha, invasive Shigella induced a narrow
      transcriptome that seems to program infected epithelial cells to recruit a
      mucosal polymorphonuclear leukocyte to infiltrate. Dramatic increase in IL-8 gene
      transcription points to this chemokine as the major molecule orchestrating
      mucosal inflammation in shigellosis.

PMID- 12813034
TI  - NF kappa B controls the balance between Fas and tumor necrosis factor cell death
      pathways during T cell receptor-induced apoptosis via the expression of its
      target gene A20.
AB  - Activation-induced cell death (AICD), a term originally coined for the anti-CD3
      induced apoptosis of T cell hybridomas and thymocytes, is predominantly driven by
      death receptors and has been involved in the control of autoreactive T cells in
      the periphery. In the Do-11.10 T cell hybridoma model of AICD, activation of the
      T cell receptor (TCR) results in Fas-dependent apoptosis. Here, we show that
      inhibition of the transcription factor nuclear factor kappa B (NF kappa B) in Do
      11.10 cells resulted in increased sensitivity to TCR-mediated apoptosis,
      correlating with defective induction of the anti-apoptotic NF kappa B target gene
      A20. Stable expression of the zinc finger protein A20 in NF kappa B-negative Do
      11.10 cells rescued the phenotype. TCR activation in NF kappa B-deficient Do
      11.10 cells resulted predominantly in tumor necrosis factor (TNF) receptor 2
      (TNFR2)-dependent bystander cell death rather than classical Fas-dependent AICD.
      Strikingly, A20 blocked TNF-mediated apoptosis and simultaneously restored TCR
      induced Fas-dependent AICD. In addition, NF kappa B downstream of TNFR was
      required for up-regulation of Fas expression by endogenous TNF secreted in
      response to TCR stimulation. Together, these results suggest that NF kappa B can
      play both pro- and anti-apoptotic roles during AICD. We propose that NF kappa B
      controls the balance between Fas and TNF cell death pathways during AICD via the
      expression of the zinc finger protein A20.

PMID- 12813035
TI  - Interferon-gamma augments CARD4/NOD1 gene and protein expression through
      interferon regulatory factor-1 in intestinal epithelial cells.
AB  - Although intestinal epithelial cells appear to be functionally hyporesponsive to
      normal intestinal flora, human intestinal epithelial cells can respond to
      enteroinvasive bacteria and induce an inflammatory response. This initial
      inflammatory response leads to the recruitment of polymorphonuclear leukocytes to
      the affected site in vitro and in vivo. CARD4/NOD1 is a potential cytosolic
      receptor for peptidoglycan in mammalian cells that resembles pathogen-resistant
      proteins of plants. In this context, CARD4/NOD1 is a candidate for a recognition
      protein of intracellular bacteria or peptidoglycan in intestinal epithelial
      cells. In this study, we demonstrate that CARD4/NOD1 is constitutively expressed
      in intestinal epithelial cell lines and isolated primary intestinal epithelial
      cells. Interferon-gamma (IFN gamma), which is a potent pro-inflammatory cytokine
      in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a
      time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein
      in SW480 cells. Promoter analysis of CARD4/NOD1 indicates that interferon
      regulatory factor-1 (IRF-1) binding motif (-791 to -782) is essential for the
      effect of IFN gamma. Nuclear extracts from SW480 cells treated with IFN gamma
      show specific binding of oligonucleotides corresponding to this IRF-1-binding
      motif, which was supershifted by anti-IRF-1 antibody in electrophoretic mobility
      shift assay. Overexpression of IRF-1 protein activates the CARD4/NOD1 promoter
      but not the deletion mutant of the IRF-1-binding site in a co-transfection assay
      of IRF-1 expression plasmid with CARD4/NOD1 promoter. These studies suggest that
      the Th1 cytokine, IFN gamma, activates CARD4/NOD1 transcription and regulate
      innate immune mechanisms in the condition of intestinal mucosal inflammation.

PMID- 12813036
TI  - Downstream DNA sequence effects on transcription elongation. Allosteric binding
      of nucleoside triphosphates facilitates translocation via a ratchet motion.
AB  - The ability of RNA polymerase (RNAP) to adopt multiple conformations is central
      to transcriptional regulation. In previous work, we demonstrated that RNAP can
      exist in an unactivated state that catalyzes synthesis slowly and an activated
      state that catalyzes synthesis rapidly, with the transition from the unactivated
      to the activated state being induced by the templated NTP binding to an
      allosteric site on the RNAP. In this work, we investigate the effects of
      downstream DNA sequences on the kinetics of single nucleotide incorporation. We
      demonstrate that changing the identity of the DNA base 1 bp downstream (+2) from
      the site of incorporation (+1) can regulate the catalytic activity of RNAP.
      Combining these data with sequence and structural analyses and molecular
      modeling, we identify the streptolydigin-binding region (Escherichia coli beta
      residues 543-546), which lies across from the downstream DNA, as the putative
      allosteric NTP binding site. We present a structural model in which the NTP binds
      to the streptolydigin loop and upon pairing with the +1 DNA base in the
      unactivated state or the +2 DNA base in the activated state facilitates
      translocation via a ratchet motion. This model provides an alternative mechanism
      for pausing as well as a structural explanation not only for our kinetic data but
      also for data from elongation studies on yeast RNAP II.

PMID- 12813037
TI  - Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human
      Niemann-Pick type C disease.
AB  - The cholesterol trafficking defect in Niemann-Pick type C (NPC) disease leads to
      impaired regulation of cholesterol esterification, cholesterol synthesis, and low
      density lipoprotein receptor activity. The ATP-binding cassette transporter A1
      (ABCA1), which mediates the rate-limiting step in high density lipoprotein (HDL)
      particle formation, is also regulated by cell cholesterol content. To determine
      whether the Niemann-Pick C1 protein alters the expression and activity of ABCA1,
      we determined the ability of apolipoprotein A-I (apoA-I) to deplete pools of
      cellular cholesterol and phospholipids in human fibroblasts derived from NPC1+/+,
      NPC1+/-, and NPC1-/- subjects. Efflux of low density lipoprotein-derived, non
      lipoprotein, plasma membrane, and newly synthesized pools of cell cholesterol by
      apoA-I was diminished in NPC1-/- cells, as was efflux of phosphatidylcholine and
      sphingomyelin. NPC1+/- cells showed intermediate levels of lipid efflux compared
      with NPC1+/+ and NPC1-/- cells. Binding of apoA-I to cholesterol-loaded and non
      cholesterol-loaded cells was highest for NPC1+/- cells, with NPC1+/+ and NPC1-/-
      cells showing similar levels of binding. ABCA1 mRNA and protein levels increased
      in response to cholesterol loading in NPC1+/+ and NPC1+/- cells but showed low
      levels at base line and in response to cholesterol loading in NPC1-/- cells.
      Consistent with impaired ABCA1-dependent lipid mobilization to apoA-I for HDL
      particle formation, we demonstrate for the first time decreased plasma HDL
      cholesterol levels in 17 of 21 (81%) NPC1-/- subjects studied. These results
      indicate that the cholesterol trafficking defect in NPC disease results in
      reduced activity of ABCA1, which we suggest is responsible for the low HDL
      cholesterol in the majority of NPC subjects and partially responsible for the
      overaccumulation of cellular lipids in this disorder.

PMID- 12813038
TI  - Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced
      transcription during stress.
AB  - Heat shock factor 2 (HSF2) belongs to a family of structurally related
      transcription factors, which share the property of binding to heat shock elements
      in the promoters of hsp molecular chaperone genes. However, unlike HSF1, which is
      essential for hsp gene transcription, the cellular functions of HSF2 are not well
      known. Here we show that human HSF2, although an ineffective activator of the
      hsp70 promoter in vitro and in vivo in the absence of stress, participates in the
      activation of the hsp70 promoter by heat shock. HSF2 was not, however, activated
      by heat shock in cells deficient in functional HSF1, suggesting a requirement for
      HSF1 in HSF2-mediated transcriptional enhancement. In addition, HSF2 regulation
      involves differential activity of two isoforms, HSF2A and HSF2B, which arise from
      alternative splicing of a common hsf2 gene. Under basal conditions, both HSF2
      isoforms are ineffective in activating the hsp70 transcription. However, heat
      shock differentially activates HSF2A in vivo. This phenomenon appears to be
      physiologically significant, as human myeloprogenitor cells differentiating along
      the erythroid lineage express HSF2A de novo and undergo a large increase in
      capacity to activate the hsp70 promoter. Our experiments further show that HSF1
      is physically associated with HSF2 in the cell and that such binding is enhanced
      by heat shock. Our data suggest a mechanism involving the formation of
      heterocomplexes between HSF1 and HSF2 with enhanced activity to activate the
      hsp70 promoter when compared with HSF1 or HSF2 homotrimers.

PMID- 12813039
TI  - Surface-exposed tryptophan residues are essential for O-acetylserine
      sulfhydrylase structure, function, and stability.
AB  - O-Acetylserine sulfhydrylase is a homodimeric enzyme catalyzing the last step of
      cysteine biosynthesis via a Bi Bi ping-pong mechanism. The subunit is composed of
      two domains, each containing one tryptophan residue, Trp50 in the N-terminal
      domain and Trp161 in the C-terminal domain. Only Trp161 is highly conserved in
      eucaryotes and bacteria. The coenzyme pyridoxal 5'-phosphate is bound in a cleft
      between the two domains. The enzyme undergoes an open to closed conformational
      transition upon substrate binding. The effect of single Trp to Tyr mutations on O
      acetylserine sulfhydrylase structure, function, and stability was investigated
      with a variety of spectroscopic techniques. The mutations do not significantly
      alter the enzyme secondary structure but affect the catalysis, with a predominant
      influence on the second half reaction. The W50Y mutation strongly affects the
      unfolding pathway due to the destabilization of the intersubunit interface. The
      W161Y mutation, occurring in the C-terminal domain, produces a reduction of the
      accessibility of the active site to acrylamide and stabilizes thermodynamically
      the N-terminal domain, a result consistent with stronger interdomain
      interactions.

PMID- 12813040
TI  - The immunosuppressant FK506 uncovers a positive regulatory cross-talk between the
      Hog1p and Gcn2p pathways.
AB  - The immunosuppressant Tacrolimus (FK506) has increased the survival rates of
      organ transplantation. FK506 exerts its immunosuppressive effect by inhibition of
      the protein phosphatase calcineurin in activated T-cells. Unfortunately, FK506
      therapy is associated with undesired non-therapeutic effects involving targets
      other than calcineurin. To identify these targets we have addressed FK506
      cellular toxicity in budding yeast. We show that FK506 increased cell sensitivity
      upon osmotic challenge independently of calcineurin and the FK506-binding
      proteins Fpr1p, -2p, -3p, and -4p. FK506 also induced strong amino acid
      starvation and activation of the general control (GCN) pathway. Tryptophan
      prototrophy or excess tryptophan overcame FK506 toxicity, showing that tryptophan
      deprivation mediated this effect. Mutation of the GCN3 and -4 genes partially
      alleviated FK506 toxicity, suggesting that activation of the GCN pathway by FK506
      was also involved in osmotic tolerance. FK506 enhanced osmotic stress-dependent
      Hog1p kinase phosphorylation that was not accompanied by induction of a Hog1p
      dependent reporter. Interestingly, deletion of the GCN2 gene suppressed FK506
      dependent Hog1p hyperphosphorylation and restored Hog1p-dependent reporter
      activity. Conversely, deletion of the HOG1 gene impaired FK506-dependent
      activation of Gcn2p kinase and translation of a GCN4-LacZ reporter, highlighting
      functional cross-talk between the Gcn2p and Hog1p protein kinases. Taken
      together, these data demonstrate that both FK506-induced amino acid starvation
      and activation of the GCN pathway contribute to cell sensitivity to osmotic
      stress and reveal a positive regulatory loop between the Hog1p and Gcn2p
      pathways. Given the conserved nature of Gcn2p and Hog1p pathways, this mechanism
      of FK506 toxicity could be relevant to the non-therapeutic effects of FK506
      therapy.

PMID- 12813041
TI  - A negatively charged amino acid in Skp2 is required for Skp2-Cks1 interaction and
      ubiquitination of p27Kip1.
AB  - Proteolysis of cyclin-dependent kinase inhibitor p27 occurs predominantly in the
      late G1 phase of the cell cycle through a ubiquitin-mediated protein degradation
      pathway. Ubiquitination of p27 requires the SCFSkp2 ubiquitin ligase and Skp2 F
      box binding protein Cks1. The mechanisms by which Skp2 recognizes Cks1 to
      ubiquitylate p27 remain obscure. Here we show that Asp-331 in the carboxyl
      terminus of Skp2 is required for its association with Cks1 and ubiquitination of
      p27. Mutation of Asp-331 to Ala disrupts the interaction between Skp2 and Cks1.
      Although Asp-331 mutation negates the ability of the Skp1-Cullin-F-box protein
      (SCF) complex to ubiquitylate p27, such a mutation has no effect on Skp2 self
      ubiquitination. A conservative change from Asp to Glu at position 331 of Skp2
      does not affect Skp2-Cks1 interaction. Our results revealed a unique requirement
      for a negatively charged residue in the carboxyl-terminal region of Skp2 in
      recognition of Cks1 and ubiquitination of p27.

PMID- 12813042
TI  - Evidence for the proteolytic processing of dentin matrix protein 1.
      Identification and characterization of processed fragments and cleavage sites.
AB  - Full-length cDNA coding for dentin matrix protein 1 (DMP1) has been cloned and
      sequenced, but the corresponding complete protein has not been isolated. In
      searching for naturally occurring DMP1, we recently discovered that the
      extracellular matrix of bone contains fragments originating from DMP1. Shortened
      forms of DMP1, termed 37K and 57K fragments, were treated with alkaline
      phosphatase and then digested with trypsin. The resultant peptides were purified
      by a two-dimensional method: size exclusion followed by reversed-phase high
      performance liquid chromatography. Purified peptides were sequenced by Edman
      degradation and mass spectrometry, and the sequences compared with the DMP1
      sequence predicted from cDNA. Extensive sequencing of tryptic peptides revealed
      that the 37K fragments originated from the NH2-terminal region, and the 57K
      fragments were from the COOH-terminal part of DMP1. Phosphate analysis indicated
      that the 37K fragments contained 12 phosphates, and the 57K fragments had 41.
      From 37K fragments, two peptides lacked a COOH-terminal lysine or arginine;
      instead they ended at Phe173 and Ser180 and were thus COOH termini of 37K
      fragments. Two peptides were from the NH2 termini of 57K fragments, starting at
      Asp218 and Asp222. These findings indicated that DMP1 is proteolytically cleaved
      at four bonds, Phe173-Asp174, Ser180-Asp181, Ser217-Asp218, and Gln221-Asp222,
      forming eight fragments. The uniformity of cleavages at the NH2-terminal peptide
      bonds of aspartyl residues suggests that a single proteinase is involved. Based
      on its reported specificity, we hypothesize that these scissions are catalyzed by
      PHEX protein. We envision that the proteolytic processing of DMP1 plays a crucial
      role during osteogenesis and dentinogenesis.

PMID- 12813043
TI  - Molecular basis for the different activation kinetics of the pacemaker channels
      HCN2 and HCN4.
AB  - The pacemaker channels HCN2 and HCN4 have been identified in cardiac sino-atrial
      node cells. These channels differ considerably in several kinetic properties
      including the activation time constant (tau act), which is fast for HCN2 (144 ms
      at -140 mV) and slow for HCN4 (461 ms at -140 mV). Here, by analyzing HCN2/4
      chimeras and mutants we identified single amino acid residues in transmembrane
      segments 1 and 2 and the connecting loop between S1 and S2 that are major
      determinants of this difference. Replacement of leucine 272 in S1 of HCN4 by the
      corresponding phenylalanine present in HCN2 decreased tau act of HCN4 to 149 ms.
      Conversely, activation of the fast channel HCN2 was decreased 3-fold upon the
      corresponding mutation of F221L in the S1 segment. Mutation of N291T and T293A in
      the linker between S1 and S2 of HCN4 shifted tau act to 275 ms. While residues
      272, 291, and 293 of HCN4 affected the activation speed at basal conditions they
      had no obvious influence on the cAMP-dependent acceleration of activation
      kinetics. In contrast, mutation of I308M in S2 of HCN4 abolished the cAMP
      dependent decrease in tau act. Surprisingly, this mutation also prevented the
      acceleration of channel activation observed after deletion of the C-terminal cAMP
      binding site. Taken together our results indicate that the speed of activation of
      the HCN4 channel is determined by structural elements present in the S1, S1-S2
      linker, and the S2 segment.

PMID- 12813044
TI  - Interaction codes within the family of mammalian Phox and Bem1p domain-containing
      proteins.
AB  - The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein
      interaction domain found in the atypical protein kinase C (aPKC) isoenzymes,
      lambda/iota- and zeta PKC; members of mitogen-activated protein kinase (MAPK)
      modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in
      cellular signaling. Among the last group, p62 and Par6 (partitioning-defective 6)
      are involved in coupling the aPKCs to signaling pathways involved in cell
      survival, growth control, and cell polarity. By mutation analyses and molecular
      modeling, we have identified critical residues at the interaction surfaces of the
      PB1 domains of aPKCs and p62. A basic charge cluster interacts with an acidic
      loop and helix both in p62 oligomerization and in the aPKC-p62 interaction.
      Subsequently, we determined the abilities of mammalian PB1 domain proteins to
      form heteromeric and homomeric complexes mediated by this domain. We report
      several novel interactions within this family. An interaction between the cell
      polarity scaffold protein Par6 and MEK5 was found. Furthermore, p62 interacts
      both with MEK5 and NBR1 in addition to the aPKCs. Evidence for involvement of p62
      in MEK5-ERK5 signaling is presented.

PMID- 12813045
TI  - SUMO-1/Ubc9 promotes nuclear accumulation and metabolic stability of tumor
      suppressor Smad4.
AB  - Tumor suppressor Smad4/DPC4 is a central intracellular signal transducer for
      transforming growth factor-beta (TGF-beta) signaling. We recently reported that
      transcriptional potential of Smad4 was regulated by SUMOylation in transfected
      HeLa cells (1), but the precise mechanism and function of Smad4 SUMOylation in
      TGF-beta signaling remain to be elucidated. Here, we describe the regulation of
      TGF-beta signaling by SUMOylation through the control of Smad4 metabolic
      stability and subcellular localization. We found that SUMO-1 overexpression
      strongly increases Smad4 levels, while inhibition of SUMOylation by small
      interfering RNA (siRNA)-mediated knockdown of the E2 enzyme Ubc9 reduces
      endogenous Smad4 levels. Concomitantly, SUMO-1 overexpression enhances and Ubc9
      knockdown reduces levels of intranuclear Smad4, growth inhibitory response, as
      well as transcriptional responses to TGF-beta. Comparison of wild type and mutant
      forms of Smad4 for SUMOylation, ubiquitination, and half-life allows the
      conclusion that SUMO-1 modification serves to protect Smad4 from ubiquitin
      dependent degradation and consequently enhances the growth inhibitory and
      transcriptional responses of Smad4.

PMID- 12813046
TI  - A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in
      interleukin-1 beta-stimulated synovial fibroblasts.
AB  - NF-kappa B-induced gene expression contributes significantly to the pathogenesis
      of inflammatory diseases such as arthritis. I kappa B kinase (IKK) is the
      converging point for the activation of NF-kappa B by a broad spectrum of
      inflammatory agonists and is thus a novel target for therapeutic intervention. We
      describe a small molecule, selective inhibitor of IKK-2, SC-514, which does not
      inhibit other IKK isoforms or other serine-threonine and tyrosine kinases. SC-514
      inhibits the native IKK complex or recombinant human IKK-1/IKK-2 heterodimer and
      IKK-2 homodimer similarly. IKK-2 inhibition by SC-514 is selective, reversible,
      and competitive with ATP. SC-514 inhibits transcription of NF-kappa B-dependent
      genes in IL-1 beta-induced rheumatoid arthritis-derived synovial fibroblasts in a
      dose-dependent manner. When the mechanism of NF-kappa B activation was evaluated
      in the presence of this inhibitor, several interesting observations were found.
      First, SC-514 did not inhibit the phosphorylation and activation of the IKK
      complex. Second, there was a delay but not a complete blockade in I kappa B alpha
      phosphorylation and degradation; likewise there was a slightly slowed, decreased
      import of p65 into the nucleus and a faster export of p65 from the nucleus.
      Finally, both I kappa B alpha and p65 were comparable substrates for IKK-2, with
      similar Km and Kcat values, and SC-514 inhibited the phosphorylation of either
      substrate similarly. Thus, the effect of SC-514 on cytokine gene expression may
      be a combination of inhibiting I kappa B alpha phosphorylation/degradation,
      affecting NF-kappa B nuclear import/export as well as the phosphorylation and
      transactivation of p65.

PMID- 12813047
TI  - Identification of upstream cis-acting regulatory elements controlling lineage
      specific expression of the mouse NK cell activation receptor, NKR-P1C.
AB  - Mouse NKR-P1C (NK1.1) is a homodimeric type II transmembrane protein expressed on
      natural killer (NK) cells, NKT cells, and on CD117+ progenitor thymocytes capable
      of giving rise to cells of the T and NK lineages. Although its physiological
      ligands remain unknown, NKR-P1C engagement with a monoclonal antibody (mAb) leads
      to interferon-gamma (IFN-gamma) production and the directed release of cytotoxic
      granules from NK cells. We have cloned and sequenced a approximately 10-kb
      genomic fragment corresponding to the 5'-flanking region of the C57Bl/6 mouse NKR
      P1C gene. A transcriptional initiation site has been mapped in NK cells and an
      NK1.1+ T cell line by primer extension and rapid amplification of 5'-cDNA ends
      (5'-RACE) techniques. Although the 5'-flanking region of NKR-P1C is TATA-less, we
      have identified an initiator region and a downstream promoter element, which
      together constitute the principal minimal functional promoter. Computational
      analysis of the 10-kb 5'-flanking region revealed potential regulatory factor
      binding sites. DNaseI hypersensitivity assays identified a single hypersensitive
      site (HS) about a 9-kb upstream of the transcriptional initiation site. This
      site, termed HS1, was able to act as a transcriptional enhancer element in an NK
      cell line, while minimally affecting transcription in non-NK cell lines.
      Moreover, the HS1 element was shown to function as a promoter, with a transcript
      detected only in fetal NK1.1+ cells. An additional promoter and two non-coding
      exons were also characterized. These results identify the minimal upstream cis
      acting elements, and point to a complex regulatory mechanism involved in the
      lineage-specific control of NKR-P1C expression in NK lymphocytes.

PMID- 12813048
TI  - Evidence for a role of SNX16 in regulating traffic between the early and later
      endosomal compartments.
AB  - Sorting nexins (SNXs) are a growing family of proteins characterized by the
      presence of a PX domain. The PX domain mediates membrane association by
      interaction with phosphoinositides. The SNXs are generally believed to
      participate in membrane trafficking, but information regarding the function of
      individual proteins is limited. In this report, we describe the major
      characteristics of one member, SNX16. SNX16 is a novel 343-amino acid protein
      consisting of a central PX domain followed by a potential coiled-coil domain and
      a C-terminal region. Like other sorting nexins, SNX16 associates with the
      membrane via the PX domain which interacts with the phospholipid
      phosphatidylinositol 3-phosphate. We show via biochemical and cellular studies
      that SNX16 is distributed in both early and late endosome/lysosome structures.
      The coiled-coil domain is necessary for localization to the later endosomal
      structures, as mutant SNX16 lacking this domain was found only in early
      endosomes. Trafficking of internalized epidermal growth factor was also delayed
      by this SNX16 mutant, as these cells showed a delay in the segregation of
      epidermal growth factor in the early endosome for its delivery to later
      compartments. In addition, the coiled-coil domain is shown here to be important
      for homo-oligomerization of SNX16. Taken together, these results suggest that
      SNX16 is a sorting nexin that may function in the trafficking of proteins between
      the early and late endosomal compartments.

PMID- 12813049
TI  - Characterization of FGFRL1, a novel fibroblast growth factor (FGF) receptor
      preferentially expressed in skeletal tissues.
AB  - Clones for a novel transmembrane receptor termed FGFRL1 were isolated from a
      subtracted, cartilage-specific cDNA library prepared from chicken sterna.
      Homologous sequences were identified in other vertebrates, including man, mouse,
      rat and fish, but not in invertebrates such as Caenorhabditis elegans and
      Drosophila. FGFRL1 was expressed preferentially in skeletal tissues as
      demonstrated by Northern blotting and in situ hybridization. Small amounts of the
      FGFRL1 mRNA were also detected in other tissues such as skeletal muscle and
      heart. The novel protein contained three extracellular Ig-like domains that were
      related to the members of the fibroblast growth factor (FGF) receptor family.
      However, it lacked the intracellular protein tyrosine kinase domain required for
      signal transduction by transphosphorylation. When expressed in cultured cells as
      a fusion protein with green fluorescent protein, FGFRL1 was specifically
      localized to the plasma membrane where it might interact with FGF ligands.
      Recombinant FGFRL1 protein was produced in a baculovirus system with intact
      disulfide bonds. Similar to FGF receptors, the expressed protein interacted
      specifically with heparin and with FGF2. When overexpressed in MG-63 osteosarcoma
      cells, the novel receptor had a negative effect on cell proliferation. Taken
      together our data are consistent with the view that FGFRL1 acts as a decoy
      receptor for FGF ligands.

PMID- 12813050
TI  - Role of phospholipase A2 activation and calcium in CYP2E1-dependent toxicity in
      HepG2 cells.
AB  - Previous studies suggested a role for calcium in CYP2E1-dependent toxicity. The
      possible role of phospholipase A2 (PLA2) activation in this toxicity was
      investigated. HepG2 cells that overexpress CYP2E1 (E47 cells) exposed to
      arachidonic acid (AA) +Fe-NTA showed higher toxicity than control HepG2 cells not
      expressing CYP2E1 (C34 cells). This toxicity was inhibited by the PLA2 inhibitors
      aristolochic acid, quinacrine, and PTK. PLA2 activity assessed by release of
      preloaded [3H]AA after treatment with AA+Fe was higher in the CYP2E1 expressing
      HepG2 cells. This [3H]AA release was inhibited by PLA2 inhibitors, alpha
      tocopherol, and by depleting Ca2+ from the cells (intracellular + extracellular
      sources), but not by removal of extracellular calcium alone. Toxicity was
      preceded by an increase in intracellular calcium caused by influx from the
      extracellular space, and this was prevented by PLA2 inhibitors. PLA2 inhibitors
      also blocked mitochondrial damage in the CYP2E1-expressing HepG2 cells exposed to
      AA+Fe. Ca2+ depletion and removal of extracellular calcium inhibited toxicity at
      early time periods, although a delayed toxicity was evident at later times in
      Ca2+-free medium. This later toxicity was also inhibited by PLA2 inhibitors.
      Analogous to PLA2 activity, Ca2+ depletion but not removal of extracellular
      calcium alone prevented the activation of calpain activity by AA+Fe. These
      results suggest that release of stored calcium by AA+Fe, induced by lipid
      peroxidation, can initially activate calpain and PLA2 activity, that PLA2
      activation is critical for a subsequent increased influx of extracellular Ca2+,
      and that the combination of increased PLA2 and calpain activity, increased
      calcium and oxidative stress cause mitochondrial damage, that ultimately produces
      the rapid toxicity of AA+Fe in CYP2E1-expressing HepG2 cells.

PMID- 12813051
TI  - The twin-arginine leader-binding protein, DmsD, interacts with the TatB and TatC
      subunits of the Escherichia coli twin-arginine translocase.
AB  - The twin-arginine translocase (Tat) pathway is involved in the targeting and
      translocation of fully folded proteins to the inner membrane and periplasm of
      bacteria. Proteins that use this pathway contain a characteristic twin-arginine
      signal sequence, which interacts with the receptor complex formed by the TatBC
      subunits. Recently, the DmsD protein was discovered, which binds to the twin
      arginine signal sequences of the anaerobic respiratory enzymes dimethylsulfoxide
      reductase (DmsABC) and trimethylamine N-oxide (TMAO) reductase. In this work, the
      targeting of DmsD within Escherichia coli was investigated. Using cell
      fractionation and Western blot analysis, DmsD is found to be associated with the
      inner membrane of wild-type E. coli and a dmsABC mutant E. coli under anaerobic
      conditions. In contrast, DmsD is predominantly found in the cytoplasmic fraction
      of a Delta tatABCDE strain, which suggests that DmsD interacts with the membrane
      associated Tat complex. Under aerobic conditions DmsD was also found primarily in
      the cytoplasmic fraction of wild-type E. coli, suggesting that physiological
      conditions have a significant effect upon the targeting of DmsD to the inner
      membrane. Size exclusion chromatography data and membrane washing studies
      indicate that DmsD is interacting tightly with an integral membrane protein and
      not with the lipid component of the E. coli inner membrane. Additional
      investigation into the nature of this interaction revealed that the TatB and TatC
      subunits of the translocase are important for the interaction of DmsD with the E.
      coli inner membrane.

PMID- 12813052
TI  - Disulfide cross-linking reveals a site of stable interaction between C-terminal
      regulatory domains of the two MalK subunits in the maltose transport complex.
AB  - Understanding the structure and function of the ATP-binding cassette (ABC)
      transporters is very important because defects in ABC transporters lie at the
      root of several serious diseases including cystic fibrosis. MalK, the ATP-binding
      cassette of the maltose transporter of Escherichia coli, is distinct from most
      other ATP-binding cassettes in that it contains an additional C-terminal
      regulatory domain. The published structure of a MalK dimer is elongated with C
      terminal domains at opposite poles (Diederichs, K., Diez, J., Greller, G.,
      Muller, C., Breed, J., Schnell, C., Vonrhein, C., Boos, W., and Welte, W. (2000)
      EMBO J. 19, 5951-5961). Some uncertainty exists as to whether the orientation of
      MalK in the dimer structure is correct. Superpositioning of the N-terminal
      domains of MalK onto the ATP-binding domains of an alternate ABC dimer, in which
      ATP is bound along the dimer interface between Walker A and LSGGQ motifs, places
      both N- and C-terminal domains of MalK along the dimer interface. Consistent with
      this model, a cysteine substitution at position 313 in the C-terminal domain of
      an otherwise cysteine-free MalK triggered disulfide bond formation between two
      MalK subunits in an intact maltose transporter. Disulfide bond formation did not
      inhibit the function of the transporter, suggesting that the C-terminal domains
      of MalK remain in close proximity throughout the transport cycle. Enzyme IIAglc
      still inhibited the ATPase activity of the disulfide-linked transporter
      indicating that the mechanism of inducer exclusion was unaffected. These data
      support a model for ATP hydrolysis in which the C-terminal domains of MalK remain
      in contact whereas the N-terminal domains of MalK open and close to allow
      nucleotide binding and dissociation.

PMID- 12813053
TI  - Dissociation of cytochrome c from the inner mitochondrial membrane during cardiac
      ischemia.
AB  - Mitochondria isolated from ischemic cardiac tissue exhibit diminished rates of
      respiration and ATP synthesis. The present study was undertaken to determine
      whether cytochrome c release was responsible for ischemia-induced loss in
      mitochondrial function. Rat hearts were perfused in Langendorff fashion for 60
      min (control) or for 30 min followed by 30 min of no flow ischemia. Mitochondria
      isolated from ischemic hearts in a buffer containing KCl exhibited depressed
      rates of maximum respiration and a lower cytochrome c content relative to control
      mitochondria. The addition of cytochrome c restored maximum rates of respiration,
      indicating that the release of cytochrome c is responsible for observed declines
      in function. However, mitochondria isolated in a mannitol/sucrose buffer
      exhibited no ischemia-induced loss in cytochrome c content, indicating that
      ischemia does not on its own cause the release of cytochrome c. Nevertheless,
      state 3 respiratory rates remained depressed, and cytochrome c release was
      enhanced when mitochondria from ischemic relative to perfused tissue were
      subsequently placed in a high ionic strength buffer, hypotonic solution, or
      detergent. Thus, events that occur during ischemia favor detachment of cytochrome
      c from the inner membrane increasing the pool of cytochrome c available for
      release. These results provide insight into the sequence of events that leads to
      release of cytochrome c and loss of mitochondrial respiratory activity during
      cardiac ischemia/reperfusion.

PMID- 12813054
TI  - Chloroquine resistance modulated in vitro by expression levels of the Plasmodium
      falciparum chloroquine resistance transporter.
AB  - Plasmodium falciparum malaria is increasingly difficult to treat and control due
      to the emergence of parasite resistance to the major antimalarials, notably
      chloroquine. Recent work has shown that the chloroquine resistance phenotype can
      be conferred by multiple amino acid mutations in the parasite digestive vacuole
      transmembrane protein PfCRT. Here, we have addressed whether chloroquine
      resistance can also be affected by changes in expression levels of this protein.
      Transient transfection reporter assays revealed that truncation of the pfcrt 3'
      untranslated region just prior to putative polyadenylation sites resulted in a 10
      fold decrease in luciferase expression levels. Using allelic exchange on a
      chloroquine-resistant line (7G8 from Brazil), this truncated 3'-untranslated
      region was inserted downstream of the pfcrt coding sequence, in the place of the
      endogenous 3'-untranslated region. The resulting pfcrt-modified "knockdown"
      clones displayed a marked decrease in pfcrt transcription and an estimated 30-40%
      decrease in PfCRT protein expression levels. [3H]hypoxanthine incorporation
      assays demonstrated up to a 40% decrease in chloroquine with or without verapamil
      IC50 levels of pfcrt knockdown clones, relative to the 7G8 parent. Single-cell
      photometric analyses were consistent with an altered intracellular pH in the
      knockdown clones, providing further evidence for a relationship between PfCRT, pH
      regulation, and chloroquine resistance. Genetic truncation of 3'-untranslated
      regions provides a useful approach for assessing the impact of candidate genes on
      drug resistance or other quantifiable phenotypes in P. falciparum.

PMID- 12813055
TI  - Signaling role for phospholipase C gamma 2 in platelet glycoprotein Ib alpha
      calcium flux and cytoskeletal reorganization. Involvement of a pathway distinct
      from FcR gamma chain and Fc gamma RIIA.
AB  - Interaction of the platelet GPIb-V-IX complex with surface immobilized von
      Willebrand factor (vWf) is required for the capture of circulating platelets and
      their ensuing activation. In previous work, it was found that GPIb/vWf-mediated
      platelet adhesion triggers Ca2+ release from intracellular stores, leading to
      cytoskeletal reorganization and filopodia extension. Despite the potential
      functional importance of GPIb-induced cytoskeletal changes, the signaling
      mechanisms regulating this process have remained ill-defined. The studies
      presented here demonstrate an important role for phospholipase C (PLC)-dependent
      phosphoinositide turnover for GPIb-dependent cytoskeletal remodeling. This is
      supported by the findings that the vWf-GPIb interaction induced a small increase
      in inositol 1,4,5-triphosphate (IP3) and that treating platelets with the IP3
      receptor antagonist APB-2 or the PLC inhibitor U73122 blocked cytosolic Ca2+ flux
      and platelet shape change. Normal shape change was observed in G alpha q-/- mouse
      platelets, excluding a role for PLC beta isoforms in this process. However,
      decreased shape change and Ca2+ mobilization were observed in mice lacking PLC
      gamma 2, demonstrating that this isotype played an important, albeit incomplete,
      role in GPIb signaling. The signaling pathways utilized by GPIb involved one or
      more members of the Src kinase family as platelet shape change and Ca2+ flux were
      inhibited by the Src kinase inhibitors PP1 and PP2. Strikingly, shape change and
      Ca2+ release occurred independently of immunoreceptor tyrosine-based activation
      motif (ITAM)-containing receptors, because these platelet responses were normal
      in human platelets treated with the anti-Fc gamma RIIA blocking monoclonal
      antibody IV.3 and in mouse platelets deficient in the FcR gamma chain. Taken
      together, these studies define an important role for PLC gamma 2 in GPIb
      signaling linked to platelet shape change. Moreover, they demonstrate that GPIb
      dependent calcium flux and cytoskeletal reorganization involves a signaling
      pathway distinct from that utilized by ITAM-containing receptors.

PMID- 12813056
TI  - Distinct regions of human glycophorin A enhance human red cell anion exchanger
      (band 3; AE1) transport function and surface trafficking.
AB  - Human red cell glycophorin A (GPA) enhances the expression of band 3 anion
      transport activity at the cell surface of Xenopus oocytes. This effect of GPA
      could occur in two ways, enhancement of band 3 anion transport function or
      enhancement of band 3 trafficking to the cell surface. We have examined the GPA
      effect using GPA mutants. We compared the sequences of GPA and its homolog
      glycophorin B (GPB; which does not facilitate band 3 cell-surface activity or
      trafficking) to identify candidate regions of GPA for study. We constructed
      several GPA or GPB mutants, including naturally occurring GPA/GPB hybrid
      molecules and insertion, deletion, and substitution mutants. We analyzed the
      effects of the mutant proteins on band 3-specific chloride transport and surface
      presentation using co-expression in Xenopus oocytes. We find that the C-terminal
      cytoplasmic tail of GPA enhances trafficking of band 3 to the cell surface,
      whereas the extracellular residues 68-70 increase the specific anion transport
      activity of band 3. In addition, examination of the oligomerization of GPA
      mutants showed that single amino acid substitutions N-terminal to the
      transmembrane domain greatly reduce SDS-stable GPA dimer formation, implying that
      regions outside the transmembrane domain of GPA are important for GPA dimer
      formation.

PMID- 12813057
TI  - Saposin C is required for normal resistance of acid beta-glucosidase to
      proteolytic degradation.
AB  - Saposins (A, B, C, and D) are small sphingolipid activator proteins that are
      derived by proteolytic processing of a common precursor, prosaposin. In the
      lysosomal sphingolipid degradation pathway, acid beta-glucosidase (GCase)
      requires saposin C for optimal in vitro and in vivo hydrolysis of
      glucocerebroside. The deficiency of prosaposin/saposins (PS-/-) in humans and
      mice leads to a decrease of GCase activity in selected tissues. Concordant
      decreases (>50%) of GCase protein and in vitro activity were detected in extracts
      of cultured fibroblasts and hepatocytes from PS-/- mice and human prosaposin
      deficient fibroblasts. GCase RNA in the PS-/- cells was at wild-type levels.
      Compared with that in wild-type cells (t(1/2) >24 h), the GCase protein in the PS
      /- cells had a faster disappearance rate (t(1/2) approximately 1 h in mouse and
      approximately 8 h in human) as determined by metabolic labeling and
      immunoprecipitation with anti-GCase antibodies. Treatment of PS-/- cells with
      leupeptin, an inhibitor of cysteine proteases, led to significant increases
      (approximately 2-fold) in GCase protein and in vitro activity. Loading saposin C
      to human PS-/- fibroblasts resulted in an enhancement of GCase protein and in
      vitro activity. Saposin D loading had no effect. These data indicate that saposin
      C is required for GCase resistance to proteolytic degradation in the cell. Thus,
      diminished in vivo GCase activity would be greater than expected only from the
      lack of GCase activation by saposin C. These results indicate a new property for
      saposin C, an anti-proteolytic protective function toward GCase.

PMID- 12813058
TI  - Ferritins can regulate the secretion of apolipoprotein B.
AB  - Apolipoprotein B is secreted with atherogenic lipids as lipoprotein particles
      from hepatocytes. Regulation of the secretion of apolipoprotein B is largely post
      translational and reflects the balance between processes that leads to particle
      assembly or to intracellular degradation. Previously, we conducted a proteomic
      screen to find proteins that bind apolipoprotein B in rat liver microsomes. We
      identified ferritin heavy and light chains in this screen among other proteins
      and showed that the two ferritins bind apolipoprotein B directly in vitro. In
      hepatocytes and other cells, ferritin heavy and light chains form cytosolic cages
      that store iron. We now show that ferritin heavy or light chains post
      translationally inhibit the secretion of apolipoprotein B without altering the
      export of other hepatic proteins including albumin, factor XIII, and
      apolipoprotein A-I. This inhibition of apolipoprotein B secretion is not due to
      diminished lipid synthesis and can be partially overcome by stimulating
      triglyceride synthesis. The block in apolipoprotein B secretion by ferritins
      leads to an increase in endoplasmic reticulum-associated degradation of the
      apolipoprotein. Thus, despite being cytosolic proteins without known chaperone
      activity, ferritins can specifically regulate the secretion of apolipoprotein B
      post-translationally. The metabolic pathways for iron storage and intercellular
      cholesterol and triglyceride transport could intersect.

PMID- 12813059
TI  - Extremophiles 2002.

PMID- 12813060
TI  - Mutants suppressing novobiocin hypersensitivity of a mukB null mutation.
AB  - The mukB gene is essential for the partitioning of sister chromosomes in
      Escherichia coli. A mukB null mutant is hypersensitive to the DNA gyrase
      inhibitor novobiocin. In this work, we isolated mutants suppressing the
      novobiocin hypersensitivity of the mukB null mutation. All suppressor mutations
      are localized in or near the gyrB gene, and the four tested clones have an amino
      acid substitution in the DNA gyrase beta subunit. We found that in the mukB
      mutant, the process of sister chromosome segregation is strikingly hypersensitive
      to novobiocin; however, the effect of novobiocin on growth, which was measured by
      culture turbidity, is the same as that of the wild-type strain.

PMID- 12813061
TI  - Identification and molecular characterization of the Mg2+ stimulon of Escherichia
      coli.
AB  - Transcription profile microarray analysis in Escherichia coli was performed to
      identify the member genes of the Mg(2+) stimulon that respond to the availability
      of external Mg(2+) in a PhoP/PhoQ two-component system-dependent manner. The mRNA
      levels of W3110 in the presence of 30 mM MgCl(2), WP3022 (phoP defective), and
      WQ3007 (phoQ defective) were compared with those of W3110 in the absence of
      MgCl(2). The expression ratios of a total of 232 genes were <0.75 in all three
      strains (the supplemental data are shown at
      http://www.nara.kindai.ac.jp/nogei/seiken/array.html), suggesting that the
      PhoP/PhoQ system is involved directly or indirectly in the transcription of these
      genes. Of those, 26 contained the PhoP box-like sequences with the direct repeats
      of (T/G)GTTTA within 500 bp upstream of the initiation codon. Furthermore, S1
      nuclease assays of 26 promoters were performed to verify six new Mg(2+) stimulon
      genes, hemL, nagA, rstAB, slyB, vboR, and yrbL, in addition to the phoPQ, mgrB,
      and mgtA genes reported previously. In gel shift and DNase I footprinting assays,
      all of these genes were found to be regulated directly by PhoP. Thus, we
      concluded that the phoPQ, mgrB, mgtA, hemL, nagA, rstAB, slyB, vboR, and yrbL
      genes make up the Mg(2+) stimulon in E. coli.

PMID- 12813062
TI  - Mgr, a novel global regulator in Staphylococcus aureus.
AB  - The virulence determinants of Staphylococcus aureus are coordinately controlled
      by several unlinked chromosomal loci. Here, we report the identification of
      CYL5614, derived from strain Becker, with a mutation that affects the expression
      of type 8 capsular polysaccharide (CP8), nuclease, alpha-toxin, coagulase,
      protease, and protein A. This novel locus, named mgr, was linked by transposon
      Tn917 and mapped by three-factorial transduction crosses. The region containing
      the mgr locus was cloned and sequenced. Deletion mutagenesis and genetic
      complementation showed that the locus consisted of one gene, mgrA. Interestingly,
      mgrA-null mutants exhibited a phenotype opposite to that of CYL5614. This was due
      to a T-to-C mutation upstream of mgrA that resulted in a four- to eightfold
      increase in mgrA transcription in strain CYL5614. Thus, these results indicate
      that mgrA is an activator of CP8 and nuclease but a repressor of alpha-toxin,
      coagulase, protease, and protein A. In addition, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analyses showed that the mgr locus profoundly
      affected extracellular protein production, suggesting that the locus may regulate
      many other genes as well. The translated MgrA protein has a region of significant
      homology, which includes the helix-turn-helix DNA-binding motif, with the
      Escherichia coli MarR family of transcriptional regulators. Northern slot blot
      analyses suggested that mgr affected CP8, alpha-toxin, nuclease, and protein A at
      the transcriptional level.

PMID- 12813063
TI  - Electrophoretic mobility of Bacillus subtilis knockout mutants with and without
      flagella.
AB  - Mutants of Bacillus subtilis 168 strain were obtained by inactivation of a
      specific gene by homologous recombination with the plasmid pMutinT3. The cell
      surface properties of these strains were characterized by measuring the
      electrophoretic mobility of the cells as a function of pH and ionic strength. The
      surface properties were different for the strains possessing flagella on their
      cells and strain FlgB, having no flagellum, due to knockout of the corresponding
      gene. The cell surface properties of the strains possessing flagella become
      similar to those of strain FlgB after acid treatment. It was confirmed that the
      acid treatment degraded the flagella without causing any apparent structural
      change on the cell surface via observations made using atomic force microscopy,
      transmission electron microscopy, and scanning electron microscopy. These results
      indicate that the flagella are a key factor influencing cell surface properties.

PMID- 12813064
TI  - Repression of phenazine antibiotic production in Pseudomonas aureofaciens strain
      30-84 by RpeA.
AB  - Pseudomonas aureofaciens strain 30-84 is a biological control bacterium that
      utilizes a two-component GacS/GacA regulatory system interconnected with the
      PhzR/PhzI quorum sensing system to positively regulate biosynthesis of phenazine
      antibiotics that contribute to its association with plant hosts. To date, no
      negative regulators of phenazine production have been identified, nor has the
      role of repression been studied. Here we describe a novel repressor of secondary
      metabolism in P. aureofaciens strain 30-84, RpeA, whose deduced amino acid
      sequence is similar to those of a group of putative two-component regulatory
      systems of unknown function found in several animal and plant-pathogenic
      bacteria. In minimal medium where phenazine production is very low, inactivation
      of the rpeA gene enhanced phenazine biosynthetic gene expression and increased
      phenazine production but did not increase quorum sensing signal accumulation.
      Furthermore, RpeA functioned to block phenazine biosynthetic gene transcription
      in minimal medium even when quorum-sensing signals were at a level that was
      sufficient for induction of phenazine gene expression in rich medium.
      Additionally, in the absence of rpeA, the quorum sensor PhzR was not required for
      phenazine production. Although repression plays a critical role in phenazine
      regulation, the rpeA mutation could not bypass the requirement for a functional
      GacS/GacA system, demonstrating that activation is required even in the absence
      of the RpeA repressor. This study reinforces that multiple signals, including
      nutrition and population density, are integrated to control the appropriate
      expression of phenazine antibiotics.

PMID- 12813066
TI  - Molecular analysis of transport and oligomerization of the Yersinia
      enterocolitica adhesin YadA.
AB  - The Yersinia adhesin YadA is the prototype of a novel class of bacterial adhesins
      which form oligomeric lollipop-like structures and are anchored in the outer
      membrane by the C terminus. For YadA, six different regions (R) or domains (D)
      are predicted from the amino acid sequence: the N-terminal leader sequence, head
      D, neck-D, stalk-D, linking-R, and a C-terminal transmembrane region consisting
      of four beta-strands. To identify structural and functional features of these
      domains, we performed in-frame deletion mutagenesis and constructed N-terminally
      tagged YadA variants. Diverse YadA variants were analyzed for outer membrane
      localization, surface exposure, oligomerization adhesion properties, and ability
      to protect against complement-mediated lysis. We demonstrated that (i) the C
      terminal region (amino acids [aa] 353 to 422) is sufficient for outer membrane
      insertion and formation of trimers in the outer membrane; (ii) the head, neck,
      and stalk domains (aa 26 to 330) are surface exposed, forming a passenger domain;
      and (iii) the linking region (aa 331 to 369) is responsible for outer membrane
      translocation of the passenger domain. Thus, YadA meets all the criteria of an
      autotransporter. The same may be true for all other members of the YadA family,
      forming a subfamily of surface-attached oligomeric autotransporters. Moreover, in
      frame truncation mutagenesis suggested that the head and neck domains together
      form the YadA-binding module which is located on the top of the stalk. However,
      the YadA-binding module did not confer serum resistance. Mutants lacking the head
      and neck domain were resistant to complement-mediated lysis. In-frame truncation
      of the stalk domain did not result in significant attenuation of the mutant in an
      orogastric mouse infection model.

PMID- 12813065
TI  - Probing the catalytic activity of a cell division-specific transpeptidase in vivo
      with beta-lactams.
AB  - Penicillin-binding protein 3 (PBP3; also called FtsI) is a transpeptidase that
      catalyzes cross-linking of the peptidoglycan cell wall in the division septum of
      Escherichia coli. To determine whether the catalytic activity of PBP3 is
      activated during division, we assayed acylation of PBP3 with three beta-lactams
      (cephalexin, aztreonam, and piperacillin) in growing cells. Acylation of PBP3
      with cephalexin, but not aztreonam or piperacillin, appeared to be stimulated by
      cell division. Specifically, cephalexin acylated PBP3 about 50% faster in a
      population of dividing cells than in a population of filamentous cells in which
      division was inhibited by inactivation or depletion of FtsZ, FtsA, FtsQ, FtsW, or
      FtsN. However, in a simpler in vitro system using isolated membranes, acylation
      with cephalexin was not impaired by depletion of FtsW or FtsN. A conflicting
      previous report that the ftsA3(Ts) allele interferes with acylation of PBP3 was
      found to be due to the presence of a thermolabile PBP3 in the strain used in that
      study. The new findings presented here are discussed in light of the hypothesis
      that the catalytic activity of PBP3 is stimulated by interaction(s) with other
      division proteins. We suggest that there might be allosteric activation of
      substrate binding.

PMID- 12813067
TI  - Sites of interaction between the FecA and FecR signal transduction proteins of
      ferric citrate transport in Escherichia coli K-12.
AB  - Transcription of the fecABCDE ferric citrate transport genes of Escherichia coli
      K-12 is initiated by a signaling cascade from the cell surface into the
      cytoplasm. FecR receives the signal in the periplasm from the outer membrane
      protein FecA loaded with ferric citrate, transmits the signal across the
      cytoplasmic membrane, and converts FecI in the cytoplasm to an active sigma
      factor. In this study, it was shown through the use of a bacterial two-hybrid
      system that, in the periplasm, the C-terminal FecR(237-317) fragment interacts
      with the N-terminal FecA(1-79) fragment. In the same C-terminal region, amino
      acid residues important for the interaction of FecR with FecA were identified by
      random and site-directed mutagenesis. They were preferentially located in and
      around a leucine motif (residues 247 to 268) which was found to be highly
      conserved in FecR-like proteins. The degree of residual binding of FecR mutant
      proteins to FecA was correlated with the degree of transcription initiation in
      response to ferric citrate in the culture medium. Three randomly generated
      inactive FecR mutants, FecR(L254E), FecR(L269G), and FecR(F284L), were suppressed
      to different degrees by the mutants FecA(G39R) and FecR(D43E). One FecR mutant,
      FecR (D138E, V197A), induced fecA promoter-directed transcription constitutively
      in the absence of ferric citrate and bound more strongly than wild-type FecR to
      FecA. The data showed that FecR interacts in the periplasm with FecA to confer
      ferric citrate-induced transcription of the fec transport genes and identified
      sites in FecR and FecA that are important for signal transduction.

PMID- 12813068
TI  - Identification and characterization of transposable elements of Paracoccus
      pantotrophus.
AB  - We studied diversity and distribution of transposable elements residing in
      different strains (DSM 11072, DSM 11073, DSM 65, and LMD 82.5) of a soil
      bacterium Paracoccus pantotrophus (alpha-Proteobacteria). With application of a
      shuttle entrapment vector pMEC1, several novel insertion sequences (ISs) and
      transposons (Tns) have been identified. They were sequenced and subjected to
      detailed comparative analysis, which allowed their characterization (i.e.,
      identification of transposase genes, terminal inverted repeats, as well as target
      sequences) and classification into the appropriate IS or Tn families. The
      frequency of transposition of these elements varied and ranged from 10(-6) to 10(
      3) depending on the strain. The copy number, localization (plasmid or
      chromosome), and distribution of these elements in the Paracoccus species P.
      pantotrophus, P. denitrificans, P. methylutens, P. solventivorans, and P.
      versutus were analyzed. This allowed us to distinguish elements that are common
      in paracocci (ISPpa2, ISPpa3--both of the IS5 family--and ISPpa5 of IS66 family)
      as well as strain-specific ones (ISPpa1 of the IS256 family, ISPpa4 of the IS5
      family, and Tn3434 and Tn5393 of the Tn3 family), acquired by lateral transfer
      events. These elements will be of a great value in the design of new genetic
      tools for paracocci, since only one element (IS1248 of P. denitrificans) has been
      described so far in this genus.

PMID- 12813070
TI  - Membrane interaction of the glycosyltransferase MurG: a special role for
      cardiolipin.
AB  - MurG is a peripheral membrane protein that is one of the key enzymes in
      peptidoglycan biosynthesis. The crystal structure of Escherichia coli MurG (S.
      Ha, D. Walker, Y. Shi, and S. Walker, Protein Sci. 9:1045-1052, 2000) contains a
      hydrophobic patch surrounded by basic residues that may represent a membrane
      association site. To allow investigation of the membrane interaction of MurG on a
      molecular level, we expressed and purified MurG from E. coli in the absence of
      detergent. Surprisingly, we found that lipid vesicles copurify with MurG. Freeze
      fracture electron microscopy of whole cells and lysates suggested that these
      vesicles are derived from vesicular intracellular membranes that are formed
      during overexpression. This is the first study which shows that overexpression of
      a peripheral membrane protein results in formation of additional membranes within
      the cell. The cardiolipin content of cells overexpressing MurG was increased from
      1 +/- 1 to 7 +/- 1 mol% compared to nonoverexpressing cells. The lipids that
      copurify with MurG were even further enriched in cardiolipin (13 +/- 4 mol%).
      MurG activity measurements of lipid I, its natural substrate, incorporated in
      pure lipid vesicles showed that the MurG activity is higher for vesicles
      containing cardiolipin than for vesicles with phosphatidylglycerol. These
      findings support the suggestion that MurG interacts with phospholipids of the
      bacterial membrane. In addition, the results show a special role for cardiolipin
      in the MurG-membrane interaction.

PMID- 12813069
TI  - Cluster of type IV secretion genes in Helicobacter pylori's plasticity zone.
AB  - Some genes present in only certain strains of the genetically diverse gastric
      pathogen Helicobacter pylori may affect its phenotype and/or evolutionary
      potential. Here we describe a new 16.3-kb segment, 7 of whose 16 open reading
      frames are homologs of type IV secretion genes (virB4, virB7 to virB11, and
      virD4), the third such putative secretion gene cluster found in H. pylori. This
      segment, to be called tfs3, was discovered by subtractive hybridization and
      chromosome walking. Full-length and truncated tfs3 elements were found in 20 and
      19%, respectively, of 94 strains tested, which were from Spain, Peru, India, and
      Japan. A tfs3 remnant (6 kb) was found in an archived stock of reference strain
      J99, although it was not included in this strain's published genome sequence. PCR
      and DNA sequence analyses indicated the following. (i) tfs3's ends are conserved.
      (ii) Right-end insertion occurred at one specific site in a chromosomal region
      that is varied in gene content and arrangement, the "plasticity zone." (iii) Left
      end insertion occurred at different sites in each of nine strains studied. (iv)
      Sequences next to the right-end target in tfs3-free strains were absent from most
      strains carrying full-length tfs3 elements. These patterns suggested insertion by
      a transposition-like event, but one in which targets are chosen with little or no
      specificity at the left end and high specificity at the right end, thereby
      deleting the intervening DNA.

PMID- 12813071
TI  - Common and distinguishing regulatory and expression characteristics of the highly
      related KorB proteins of streptomycete plasmids pIJ101 and pSB24.2.
AB  - The conjugative plasmid pIJ101 of the spore-forming bacterium Streptomyces
      lividans contains a regulatory gene, korB, whose product is required to repress
      potentially lethal expression of the pIJ101 kilB gene. The KorB protein also
      autoregulates korB gene expression and may be involved in control of pIJ101 copy
      number. KorB (pIJ101) is expressed as a 10-kDa protein in S. lividans that is
      immediately processed to a mature 6-kDa repressor molecule. The conjugative
      Streptomyces cyanogenus plasmid pSB24.1 is deleted upon entry into S. lividans to
      form pSB24.2, a nonconjugative derivative that contains a korB gene nearly
      identical to that of pIJ101. Previous evidence that korB of pSB24.2 is capable of
      overriding pIJ101 kilB-associated lethality supported the notion that pIJ101 and
      pSB24.2 encode highly related, perhaps even identical conjugation systems. Here
      we show that KorB (pIJ101) and KorB (pSB24.2) repress transcription from the
      pIJ101 kilB promoter equally well, although differences exist with respect to
      their interactions with kilB promoter sequences. Despite high sequence and
      functional similarities, KorB (pSB24.2) was found to exist as multiple stable
      forms ranging in size from 10 to 6 kDa both in S. lividans and S. cyanogenus.
      Immediate processing of KorB (pIJ101) exclusively to the 6-kDa repressor form
      meanwhile was conserved between the two species. A feature common to both
      proteins was a marked increase in expression or accumulation upon sporulation, an
      occurrence that may indicate a particular need for increased quantities of this
      regulatory protein upon spore germination and resumption of active growth of
      plasmid-containing cells.

PMID- 12813072
TI  - Ralstonia eutropha H16 encodes two and possibly three intracellular Poly[D-(-)-3
      hydroxybutyrate] depolymerase genes.
AB  - Intracellular poly[D-(-)-3-hydroxybutyrate] (PHB) depolymerases degrade PHB
      granules to oligomers and monomers of 3-hydroxybutyric acid. Recently an
      intracellular PHB depolymerase gene (phaZ1) from Ralstonia eutropha was
      identified. We now report identification of candidate PHB depolymerase genes from
      R. eutropha, namely, phaZ2 and phaZ3, and their characterization in vivo. phaZ1
      was used to identify two candidate depolymerase genes in the genome of Ralstonia
      metallidurans. phaZ1 and these genes were then used to design degenerate primers.
      These primers and PCR methods on the R. eutropha genome were used to identify two
      new candidate depolymerase genes in R. eutropha: phaZ2 and phaZ3. Inverse PCR
      methods were used to obtain the complete sequence of phaZ3, and library screening
      was used to obtain the complete sequence of phaZ2. PhaZ1, PhaZ2, and PhaZ3 share
      approximately 30% sequence identity. The function of PhaZ2 and PhaZ3 was examined
      by generating R. eutropha H16 deletion strains (Delta phaZ1, Delta phaZ2, Delta
      phaZ3, Delta phaZ1 Delta phaZ2, Delta phaZ1 Delta phaZ3, Delta phaZ2 Delta phaZ3,
      and Delta phaZ1 Delta phaZ2 Delta phaZ3). These strains were analyzed for PHB
      production and utilization under two sets of conditions. When cells were grown in
      rich medium, PhaZ1 was sufficient to account for intracellular PHB degradation.
      When cells that had accumulated approximately 80% (cell dry weight) PHB were
      subjected to PHB utilization conditions, PhaZ1 and PhaZ2 were sufficient to
      account for PHB degradation. PhaZ2 is thus suggested to be an intracellular
      depolymerase. The role of PhaZ3 remains to be established.

PMID- 12813073
TI  - Identification and mutational analysis of bacteriophage PRD1 holin protein P35.
AB  - Holin proteins are phage-induced integral membrane proteins which regulate the
      access of lytic enzymes to host cell peptidoglycan at the time of release of
      progeny viruses by host cell lysis. We describe the identification of the
      membrane-containing phage PRD1 holin gene (gene XXXV). The PRD1 holin protein
      (P35, 12.8 kDa) acts similarly to its functional counterpart from phage lambda
      (gene S), and the defect in PRD1 gene XXXV can be corrected by the presence of
      gene S of lambda. Several nonsense, missense, and insertion mutations in PRD1
      gene XXXV were analyzed. These studies support the overall conclusion that the
      charged amino acids at the protein C terminus are involved in the timing of host
      cell lysis.

PMID- 12813074
TI  - Molecular analysis of the copper-transporting efflux system CusCFBA of
      Escherichia coli.
AB  - The cus determinant of Escherichia coli encodes the CusCFBA proteins that mediate
      resistance to copper and silver by cation efflux. CusA and CusB were essential
      for copper resistance, and CusC and CusF were required for full resistance.
      Replacements of methionine residues 573, 623, and 672 with isoleucine in CusA
      resulted in loss of copper resistance, demonstrating their functional importance.
      Substitutions for several other methionine residues of this protein did not have
      any effect. The small 10-kDa protein CusF (previously YlcC) was shown to be a
      periplasmic protein. CusF bound one copper per polypeptide. The pink CusF copper
      protein complex exhibited an absorption maximum at around 510 nm. Methionine
      residues of CusF were involved in copper binding as shown by site-directed
      mutagenesis. CusF interacted with CusB and CusC polypeptides in a yeast two
      hybrid assay. In contrast to other well-studied CBA-type heavy metal efflux
      systems, Cus was shown to be a tetrapartite resistance system that involves the
      novel periplasmic copper-binding protein CusF. These data provide additional
      evidence for the hypothesis that Cu(I) is directly transported from the periplasm
      across the outer membrane by the Cus complex.

PMID- 12813075
TI  - Characterization of LytH, a differentiation-associated peptidoglycan hydrolase of
      Bacillus subtilis involved in endospore cortex maturation.
AB  - The cortex peptidoglycan from endospores of Bacillus subtilis is responsible for
      the maintenance of dormancy. LytH (YunA) has been identified as a novel
      sporulation-specific component with a role in cortex structure determination. The
      lytH gene was expressed only during sporulation, under the control of the mother
      cell-specific sigma factor sigma(K). Spores of a lytH mutant have slightly
      reduced heat resistance and altered staining when viewed by electron microscopy.
      Analysis of the peptidoglycan structure of lytH mutant spores shows the loss of
      muramic acid residues substituted with L-alanine and a corresponding increase in
      muramic acid residues substituted with tetrapeptide compared to those in the
      parent strain. In a lytH cwlD mutant, the lack of muramic acid residues
      substituted with L-alanine and delta-lactam leaves 97% of residues substituted
      with tetrapeptide. These results suggest that lytH encodes an L-Ala-D-Glu
      peptidase involved in production of single L-alanine side chains from
      tetrapeptides in the spore cortex. The lack of di- or tripeptides in a lytH
      mutant reveals the enzyme is an endopeptidase.

PMID- 12813076
TI  - The C-terminal flexible domain of the heme chaperone CcmE is important but not
      essential for its function.
AB  - CcmE is a heme chaperone active in the cytochrome c maturation pathway of
      Escherichia coli. It first binds heme covalently to strictly conserved histidine
      H130 and subsequently delivers it to apo-cytochrome c. The recently solved
      structure of soluble CcmE revealed a compact core consisting of a beta-barrel and
      a flexible C-terminal domain with a short alpha-helical turn. In order to
      elucidate the function of this poorly conserved domain, CcmE was truncated
      stepwise from the C terminus. Removal of all 29 amino acids up to crucial
      histidine 130 did not abolish heme binding completely. For detectable transfer of
      heme to type c cytochromes, only one additional residue, D131, was required, and
      for efficient cytochrome c maturation, the seven-residue sequence
      (131)DENYTPP(137) was required. When soluble forms of CcmE were expressed in the
      periplasm, the C-terminal domain had to be slightly longer to allow detection of
      holo-CcmE. Soluble full-length CcmE had low activity in cytochrome c maturation,
      indicating the importance of the N-terminal membrane anchor for the in vivo
      function of CcmE.

PMID- 12813077
TI  - Identification of pyrene-induced proteins in Mycobacterium sp. strain 6PY1:
      evidence for two ring-hydroxylating dioxygenases.
AB  - In this study, the enzymes involved in polycyclic aromatic hydrocarbon (PAH)
      degradation were investigated in the pyrene-degrading Mycobacterium sp. strain
      6PY1. [(14)C]pyrene mineralization experiments showed that bacteria grown with
      either pyrene or phenanthrene produced high levels of pyrene-catabolic activity
      but that acetate-grown cells had no activity. As a means of identifying specific
      catabolic enzymes, protein extracts from bacteria grown on pyrene or on other
      carbon sources were analyzed by two-dimensional gel electrophoresis. Pyrene
      induced proteins were tentatively identified by peptide sequence analysis. Half
      of them resembled enzymes known to be involved in phenanthrene degradation, with
      closest similarity to the corresponding enzymes from Nocardioides sp. strain KP7.
      The genes encoding the terminal components of two distinct ring-hydroxylating
      dioxygenases were cloned. Sequence analysis revealed that the two enzymes,
      designated Pdo1 and Pdo2, belong to a subfamily of dioxygenases found exclusively
      in gram-positive bacteria. When overproduced in Escherichia coli, Pdo1 and Pdo2
      showed distinctive selectivities towards PAH substrates, with the former enzyme
      catalyzing the dihydroxylation of both pyrene and phenanthrene and the latter
      preferentially oxidizing phenanthrene. The catalytic activity of the Pdo2 enzyme
      was dramatically enhanced when electron carrier proteins of the phenanthrene
      dioxygenase from strain KP7 were coexpressed in recombinant cells. The Pdo2
      enzyme was purified as a brown protein consisting of two types of subunits with
      M(r)s of about 52,000 and 20,000. Immunoblot analysis of cell extracts from
      strain 6PY1 revealed that Pdo1 was present in cells grown on benzoate,
      phenanthrene, or pyrene and absent in acetate-grown cells. In contrast, Pdo2
      could be detected only in PAH-grown cells. These results indicated that the two
      enzymes were differentially regulated depending on the carbon source used for
      growth.

PMID- 12813078
TI  - Characterization of the Vibrio vulnificus putAP operon, encoding proline
      dehydrogenase and proline permease, and its differential expression in response
      to osmotic stress.
AB  - The Vibrio vulnificus putAP genes encoding a proline dehydrogenase and a proline
      permease are transcribed in the same direction. Proline dehydrogenase activity
      and the level of putA transcript were determined to reach a maximum in
      exponential phase and were then repressed when growth slowed down. Northern
      blotting and primer extension analyses revealed that transcription of putAP genes
      results in two different transcripts, transcript A (putA transcript) and
      transcript AP (putAP transcript). Expression of putAP genes was directed by two
      promoters, promoter P(putA) and promoter P(putAP). A crp null mutation decreased
      proline dehydrogenase activity and the level of the put transcripts, indicating
      that transcription of putAP is under the positive control of cyclic AMP receptor
      protein. Proline dehydrogenase and the level of both put transcripts were
      increased by proline but repressed by glutamate. In contrast, the level of
      transcript A, not transcript AP, increased when proline dehydrogenase was induced
      by NaCl. Since P(putA) activity, not P(putAP) activity, was increased by NaCl, it
      is apparent that transcript A and transcript AP are transcribed through P(putA)
      and P(putAP), respectively. Cells challenged with NaCl and various hyperosmotic
      stresses accumulated higher levels of glutamate than control cells, indicating
      that glutamate is a compatible solute in V. vulnificus.

PMID- 12813079
TI  - Striking complexity of lipopolysaccharide defects in a collection of
      Sinorhizobium meliloti mutants.
AB  - Although the role that lipopolysaccharide (LPS) plays in the symbiosis between
      Sinorhizobium meliloti and alfalfa has been studied for over a decade, its
      function in this process remains controversial and poorly understood. This is
      largely due to a lack of mutants affected by its synthesis. In one of the
      definitive studies concerning this issue, Clover et al. (R. H. Clover, J. Kieber,
      and E. R. Signer, J. Bacteriol. 171:3961-3967, 1989) identified a series of
      mutants with putative LPS defects, judged them to be symbiotically proficient on
      Medicago sativa, and concluded that LPS might not have a symbiotic function in S.
      meliloti. The mutations in these strains were never characterized at the
      molecular level nor was the LPS from most of them analyzed. We have transduced
      these mutations from the Rm2011 background from which they were originally
      isolated into the sequenced strain Rm1021 and have characterized the resulting
      strains in greater detail. We found the LPS from these mutants to display a
      striking complexity of phenotypes on polyacrylamide electrophoresis gels,
      including additional rough LPS bands and alterations in the molecular weight
      distribution of the smooth LPS. We found that some of the mutants contain
      insertions in genes that are predicted to be involved in the synthesis of
      carbohydrate components of LPS, including ddhB, lpsB, lpsC, and lpsE. The
      majority, however, code for proteins predicted to be involved in a wide variety
      of functions not previously recognized to play a role in LPS synthesis, including
      a possible transcription elongation factor (GreA), a possible queuine synthesis
      protein, and a possible chemotaxis protein. Furthermore, using more extensive
      assays, we have found that most of these strains have symbiotic deficiencies.
      These results support more recent findings that alterations in LPS structure can
      affect the ability of S. meliloti to form an effective symbiosis.

PMID- 12813080
TI  - Functional characterization of cysteine residues in GlpT, the glycerol 3
      phosphate transporter of Escherichia coli.
AB  - In Escherichia coli, the GlpT transporter, a member of the major facilitator
      superfamily, moves external glycerol 3-phosphate (G3P) into the cytoplasm in
      exchange for cytoplasmic phosphate. Study of intact cells showed that both GlpT
      and HisGlpT, a variant with an N-terminal six-histidine tag, are inhibited (50%
      inhibitory concentration approximately 35 microM) by the hydrophilic thiol
      specific agent p-mercurichlorobenzosulfonate (PCMBS) in a substrate-protectable
      fashion; by contrast, two other thiol-directed probes, N
      maleimidylpropionylbiocytin (MPB) and [2
      (trimethylammonium)ethyl]methanethiosulfonate (MTSET), have no effect. Use of
      variants in which the HisGlpT native cysteines are replaced individually by
      serine or glycine implicates Cys-176, on transmembrane helix 5 (TM5), as the
      major target for PCMBS. The inhibitor sensitivity of purified and reconstituted
      HisGlpT or its cysteine substitution derivatives was found to be consistent with
      the findings with intact cells, except that a partial response to PCMBS was found
      for the C176G mutant, suggesting the presence of a mixed population of both right
      side-out (RSO) (resistant) and inside-out (ISO) (sensitive) orientations after
      reconstitution. To clarify this issue, we studied a derivative (P290C) in which
      the RSO molecules can be blocked independently due to an MPB-responsive cysteine
      in an extracellular loop. In this derivative, comparisons of variants with
      (P290C) and without (P290C/C176G) Cys-176 indicated that this residue shows
      substrate-protectable inhibition by PCMBS in the ISO orientation in
      proteoliposomes. Since PCMBS gains access to Cys-176 from both periplasmic and
      cytoplasmic surfaces of the protein (in intact cells and in a reconstituted ISO
      orientation, respectively) and since access is unavailable when the substrate is
      present, we propose that Cys-176 is located on the transport pathway and that TM5
      has a role in lining this pathway.

PMID- 12813081
TI  - NikAB- or NikB-dependent intracellular recombination between tandemly repeated
      oriT sequences of plasmid R64 in plasmid or single-stranded phage vectors.
AB  - The origin of transfer (oriT) of a bacterial plasmid plays a key role in both the
      initiation and termination of conjugative DNA transfer. We have previously shown
      that a conjugation-dependent recombination between the tandem R64 oriT sequences
      cloned into pHSG398 occurred, resulting in the deletion of the intervening
      sequence during DNA transfer. In this study, we tandemly cloned two oriT
      sequences of IncI1 plasmid R64 into pUC18. Specific recombination between the two
      oriT sequences in pUC18 was observed within Escherichia coli cells harboring mini
      R64. This recombination was found to be independent of both the recA gene and
      conjugative DNA transfer. The R64 genes nikA and nikB, required for conjugal DNA
      processing, were essential for this recombination. Although a fully active 92-bp
      oriT sequence was required at one site for the recombination, the 44-bp oriT core
      sequence was sufficient at the other site. Furthermore, when two oriT sequences
      were tandemly cloned into the single-stranded phage vector M13 and propagated
      within E. coli cells, recombination between the two oriT sequences was observed,
      depending on the nikB gene. These results suggest that the R64 relaxase protein
      NikB can execute cleavage and rejoining of single-stranded oriT DNA within E.
      coli cells, whereas such a reaction in double-stranded oriT DNA requires
      collaboration of the two relaxosome proteins, NikA and NikB.

PMID- 12813082
TI  - Suppressor mutations in the study of photosystem I biogenesis: sll0088 is a
      previously unidentified gene involved in reaction center accumulation in
      Synechocystis sp. strain PCC 6803.
AB  - In previous work, some members of our group isolated mutant strains of
      Synechocystis sp. strain PCC 6803 in which point mutations had been inserted into
      the psaC gene to alter the cysteine residues to the F(A) and F(B) iron-sulfur
      clusters in the PsaC subunit of photosystem I (J. P. Yu, I. R. Vassiliev, Y. S.
      Jung, J. H. Golbeck, and L. McIntosh, J. Biol. Chem. 272:8032-8039, 1997). These
      mutant strains did not grow photoautotrophically due to suppressed levels of
      chlorophyll a and photosystem I. In the results described here, we show that
      suppressor mutations produced strains that are capable of photoautotrophic growth
      at moderate light intensity (20 micromol m(-2) s(-1)). Two separate suppressor
      strains of C14S(PsaC), termed C14S(PsaC)-R62 and C14S(PsaC)-R18, were studied and
      found to have mutations in a previously uncharacterized open reading frame of the
      Synechocystis sp. strain PCC 6803 genome named sll0088. C14S(PsaC)-R62 was found
      to substitute Pro for Arg at residue 161 as the result of a G482-->C change in
      sll0088, and C14S(PsaC)-R18 was found to have a three-amino-acid insertion of Gly
      Tyr-Phe following Cys231 as the result of a TGGTTATTT duplication at T690 in
      sll0088. These suppressor strains showed near-wild-type levels of chlorophyll a
      and photosystem I, yet the serine oxygen ligand to F(B) was retained as shown by
      the retention of the S > or = 3/2 spin state of the [4Fe-4S] cluster. The
      inactivation of sll0088 by insertion of a kanamycin resistance cartridge in the
      primary C14S(PsaC) mutant produced an engineered suppressor strain capable of
      photoautotrophic growth. There was no difference in psaC gene expression or in
      the amount of PsaC protein assembled in thylakoids between the wild type and an
      sll0088 deletion mutant. The sll0088 gene encodes a protein predicted to be a
      transcriptional regulator with sequence similarities to transcription factors in
      other prokaryotic and eukaryotic organisms, including Arabidopsis thaliana. The
      protein contains a typical helix-turn-helix DNA-binding motif and can be
      classified as a negative regulator by phylogenetic analysis. This suggests that
      the product of sll0088 has a role in regulating the biogenesis of photosystem I.

PMID- 12813083
TI  - PAV1, the first virus-like particle isolated from a hyperthermophilic
      euryarchaeote, "Pyrococcus abyssi".
AB  - We describe the first virus-like particle of a hyperthermophilic euryarchaeote
      which was discovered in a strain of "Pyrococcus abyssi" previously characterized
      in our laboratory. This particle, named PAV1, is lemon-shaped (120 nm x 80 nm),
      with a short tail terminated by fibers, and resembles the virus SSV1, the type
      member of the Fuselloviridae, isolated from Sulfolobus shibatae. Sensitivity of
      the virus-like particle to organic solvents and detergents suggested that the
      envelope of PAV1 may contain lipids in addition to proteins. It contains a double
      stranded circular DNA of 18 kb which is also present in high copy number in a
      free form in the host cytoplasm. No integrated form of the PAV1 genome could be
      detected in the host chromosome. Under standard growth conditions, the host cells
      continuously release PAV1 particles into the culture supernatant without
      spontaneous lysis, with a maximum reached in the late stationary phase. UV, gamma
      irradiation, treatment with mitomycin C, and various physiological stresses had
      no effect on PAV1 production. Screening of a large number of Thermococcales
      isolates did not permit to find a sensitive host. These results suggest that PAV1
      persists in the host strain in a stable carrier state rather than a prophage.

PMID- 12813084
TI  - Expression of the nitroarene dioxygenase genes in Comamonas sp. strain JS765 and
      Acidovorax sp. strain JS42 is induced by multiple aromatic compounds.
AB  - This work reports a genetic analysis of the expression of nitrobenzene
      dioxygenase (NBDO) in Comamonas sp. strain JS765 and 2-nitrotoluene dioxygenase
      (2NTDO) in Acidovorax sp. strain JS42. Strains JS765 and JS42 possess identical
      LysR-type regulatory proteins, NbzR and NtdR, respectively. NbzR/NtdR is
      homologous to NahR, the positive salicylate-responsive transcriptional activator
      of the naphthalene degradation genes in Pseudomonas putida G7. The genes encoding
      NBDO and 2NTDO in each strain are cotranscribed, and transcription starts at the
      same site within identical promoter regions for each operon. Results from a lacZ
      reporter gene fusion demonstrated that expression of NBDO and 2NTDO is induced by
      multiple aromatic compounds, including an array of nitroaromatic compounds
      (nitrobenzene, 2-, 3-, and 4-nitrotoluene, 2,4- and 2,6-dinitrotoluene, and
      aminodinitrotoluenes), as well as salicylate and anthranilate. The nitroaromatic
      compounds appear to be the actual effector molecules. Analysis of beta
      galactosidase and 2NTDO activities with strain JS42 demonstrated that NtdR was
      required for induction by all of the inducing compounds, high basal-level
      expression of 2NTDO, and complementation of a JS42 ntdR null mutant.
      Complementation with the closely related regulators NagR (from Ralstonia sp.
      strain U2) and NahR restored only induction by the archetype inducers, salicylate
      or salicylate and anthranilate, respectively, and did not restore the high basal
      level of expression of 2NTDO. The mechanism of 2NTDO gene regulation in JS42, and
      presumably that of NBDO gene regulation in JS765, appear similar to that of NahR
      regulated genes in Pseudomonas putida G7. However, NbzR and NtdR appear to have
      evolved a broader specificity in JS42 and JS765, allowing for recognition of
      nitroaromatic compounds while retaining the ability to respond to salicylate and
      anthranilate. NtdR is also the first example of a nitroarene-responsive LysR-type
      transcriptional activator.

PMID- 12813085
TI  - Expression of spoIIIJ in the prespore is sufficient for activation of sigma G and
      for sporulation in Bacillus subtilis.
AB  - During sporulation in Bacillus subtilis, the prespore-specific developmental
      program is initiated soon after asymmetric division of the sporangium by the
      compartment-specific activation of RNA polymerase sigma factor sigma(F). sigma(F)
      directs transcription of spoIIIG, encoding the late forespore-specific regulator
      sigma(G). Following synthesis, sigma(G) is initially kept in an inactive form,
      presumably because it is bound to the SpoIIAB anti-sigma factor. Activation of
      sigma(G) occurs only after the complete engulfment of the prespore by the mother
      cell. Mutations in spoIIIJ arrest sporulation soon after conclusion of the
      engulfment process and prevent activation of sigma(G). Here we show that sigma(G)
      accumulates but is mostly inactive in a spoIIIJ mutant. We also show that
      expression of the spoIIIGE155K allele, encoding a form of sigma(G) that is not
      efficiently bound by SpoIIAB in vitro, restores sigma(G)-directed gene expression
      to a spoIIIJ mutant. Expression of spoIIIJ occurs during vegetative growth.
      However, we show that expression of spoIIIJ in the prespore is sufficient for
      sigma(G) activation and for sporulation. Mutations in the mother cell-specific
      spoIIIA locus are known to arrest sporulation just after completion of the
      engulfment process. Previous work has also shown that sigma(G) accumulates in an
      inactive form in spoIIIA mutants and that the need for spoIIIA expression for
      sigma(G) activation can be circumvented by the spoIIIGE155K allele. However, in
      contrast to the case for spoIIIJ, we show that expression of spoIIIA in the
      prespore does not support efficient sporulation. The results suggest that the
      activation of sigma(G) at the end of the engulfment process involves the action
      of spoIIIA from the mother cell and of spoIIIJ from the prespore.

PMID- 12813086
TI  - Archaeal homolog of bacterial type IV prepilin signal peptidases with broad
      substrate specificity.
AB  - A large number of secretory proteins in the thermoacidophile Sulfolobus
      solfataricus are synthesized as a precursor with an unusual leader peptide that
      resembles bacterial type IV prepilin signal sequences. This set of proteins
      includes the flagellin subunit but also various solute binding proteins. Here we
      describe the identification of the S. solfataricus homolog of bacterial type IV
      prepilin peptidases, termed PibD. PibD is an integral membrane protein that is
      phylogenetically related to the bacterial enzymes. When heterologously expressed
      in Escherichia coli, PibD is capable of processing both the flagellin and glucose
      binding protein (GlcS) precursors. Site-directed mutagenesis of the GlcS signal
      peptide shows that the substrate specificity of PibD is consistent with the
      variations found in proteins with type IV prepilin-like signal sequences of S.
      solfataricus. We conclude that PibD is responsible for the processing of these
      secretory proteins in S. solfataricus.

PMID- 12813087
TI  - Transcriptional regulation of the gene encoding an alcohol dehydrogenase in the
      archaeon Sulfolobus solfataricus involves multiple factors and control elements.
AB  - A transcriptionally active region has been identified in the 5' flanking region
      of the alcohol dehydrogenase gene of the crenarchaeon Sulfolobus solfataricus
      through the evaluation of the activity of putative transcriptional regulators and
      the role of the region upstream of the gene under specific metabolic
      circumstances. Electrophoretic mobility shift assays with crude extracts revealed
      protein complexes that most likely contain TATA box-associated factors. When the
      TATA element was deleted from the region, binding sites for both DNA binding
      proteins, such as the small chromatin structure-modeling Sso7d and Sso10b (Alba),
      and transcription factors, such as the repressor Lrs14, were revealed. To
      understand the molecular mechanisms underlying the substrate-induced expression
      of the adh gene, the promoter was analyzed for the presence of cis-acting
      elements recognized by specific transcription factors upon exposure of the cell
      to benzaldehyde. Progressive dissection of the identified promoter region
      restricted the analysis to a minimal responsive element (PAL) located immediately
      upstream of the transcription factor B-responsive element-TATA element,
      resembling typical bacterial regulatory sequences. A benzaldehyde-activated
      transcription factor (Bald) that specifically binds to the PAL cis-acting element
      was also identified. This protein was purified from heparin-fractionated extracts
      of benzaldehyde-induced cells and was shown to have a molecular mass of
      approximately 16 kDa. The correlation between S. solfataricus adh gene activation
      and benzaldehyde-inducible occupation of a specific DNA sequence in its promoter
      suggests that a molecular signaling mechanism is responsible for the switch of
      the aromatic aldehyde metabolism as a response to environmental changes.

PMID- 12813088
TI  - Whole-genome DNA microarray analysis of a hyperthermophile and an archaeon:
      Pyrococcus furiosus grown on carbohydrates or peptides.
AB  - The first complete-genome DNA microarray was constructed for a hyperthermophile
      or a nonhalophilic archaeon by using the 2,065 open reading frames (ORFs) that
      have been annotated in the genome of Pyrococcus furiosus (optimal growth
      temperature, 100 degrees C). This was used to determine relative transcript
      levels in cells grown at 95 degrees C with either peptides or a carbohydrate
      (maltose) used as the primary carbon source. Approximately 20% (398 of 2065) of
      the ORFs did not appear to be significantly expressed under either growth
      condition. Of the remaining 1,667 ORFs, the expression of 125 of them (8%)
      differed by more than fivefold between the two cultures, and 82 of the 125 (65%)
      appear to be part of operons, indicating extensive coordinate regulation. Of the
      27 operons that are regulated, 5 of them encode (conserved) hypothetical
      proteins. A total of 18 operons are up-regulated (greater than fivefold) in
      maltose-grown cells, including those responsible for maltose transport and for
      the biosynthesis of 12 amino acids, of ornithine, and of citric acid cycle
      intermediate products. A total of nine operons are up-regulated (greater than
      fivefold) in peptide-grown cells, including those encoding enzymes involved in
      the production of acyl and aryl acids and 2-ketoacids, which are used for energy
      conservation. Analyses of the spent growth media confirmed the production of
      branched-chain and aromatic acids during growth on peptides. In addition, six
      nonlinked enzymes in the pathways of sugar metabolism were regulated more than
      fivefold--three in maltose-grown cells that are unique to the unusual glycolytic
      pathway and three in peptide-grown cells that are unique to gluconeogenesis. The
      catalytic activities of 16 metabolic enzymes whose expression appeared to be
      highly regulated in the two cell types correlated very well with the microarray
      data. The degree of coordinate regulation revealed by the microarray data was
      unanticipated and shows that P. furiosus can readily adapt to a change in its
      primary carbon source.

PMID- 12813089
TI  - Characterization and functional complementation of a nonlethal deletion in the
      chromosome of a beta-glycosidase mutant of Sulfolobus solfataricus.
AB  - LacS(-) mutants of Sulfolobus solfataricus defective in beta-glycosidase activity
      were isolated in order to explore genomic instability and exploit novel
      strategies for transformation and complementation. One of the mutants showed a
      stable phenotype with no reversion; analysis of its chromosome revealed the total
      absence of the beta-glycosidase gene (lacS). Fine mapping performed in comparison
      to the genomic sequence of S. solfataricus P2 indicated an extended deletion of
      approximately 13 kb. The sequence analysis also revealed that this chromosomal
      rearrangement was a nonconservative transposition event driven by the mobile
      insertion sequence element ISC1058. In order to complement the LacS(-) phenotype,
      an expression vector was constructed by inserting the lacS coding sequence with
      its 5' and 3' flanking regions into the pEXSs plasmid. Since no transformant
      could be recovered by selection on lactose as the sole nutrient, another plasmid
      construct containing a larger genomic fragment was tested for complementation;
      this region also comprised the lacTr (lactose transporter) gene encoding a
      putative membrane protein homologous to the major facilitator superfamily. Cells
      transformed with both genes were able to form colonies on lactose plates and to
      be stained with the beta-glycosidase chromogenic substrate X-Gal (5-bromo-4
      chloro-3-indoyl-beta-D-galactopyranoside).

PMID- 12813090
TI  - Physiological responses of the hyperthermophilic archaeon "Pyrococcus abyssi" to
      DNA damage caused by ionizing radiation.
AB  - The mechanisms by which hyperthermophilic Archaea, such as "Pyrococcus abyssi"
      and Pyrococcus furiosus, survive high doses of ionizing gamma irradiation are not
      thoroughly elucidated. Following gamma-ray irradiation at 2,500 Gy, the
      restoration of "P. abyssi" chromosomes took place within chromosome
      fragmentation. DNA synthesis in irradiated "P. abyssi" cells during the DNA
      repair phase was inhibited in comparison to nonirradiated control cultures,
      suggesting that DNA damage causes a replication block in this organism. We also
      found evidence for transient export of damaged DNA out of irradiated "P. abyssi"
      cells prior to a restart of chromosomal DNA synthesis. Our cell fractionation
      assays further suggest that "P. abyssi" contains a highly efficient DNA repair
      system which is continuously ready to repair the DNA damage caused by high
      temperature and/or ionizing radiation.

PMID- 12813091
TI  - Purification and characterization of a monooxygenase involved in the biosynthetic
      pathway of the antitumor drug mithramycin.
AB  - A monooxygenase encoded by the mtmOIV gene from the mithramycin gene cluster of
      Streptomyces argillaceus was purified 21-fold by a three-step purification
      procedure. This monooxygenase catalyzes the oxidative cleavage of the fourth ring
      of premithramycin B. The enzyme was dependent on NADPH and flavin adenine
      dinucleotide for activity with optimal pH at 9.5, and the K(m) values for NADPH
      and premithramycin B were 269.22 and 23.35 micro M, respectively. The reaction
      catalyzed by MtmOIV yields two possible isomers of the same basic shortened
      aliphatic chain molecule. One of the reaction products showed important
      biological activity, thus highlighting the importance of the cleavage of the
      fourth ring of the aglycon for biological activity.

PMID- 12813092
TI  - Genome analysis of a novel Shiga toxin 1 (Stx1)-converting phage which is closely
      related to Stx2-converting phages but not to other Stx1-converting phages.
AB  - Two Stx-converting phages, designated Stx1 phi and Stx2 phi-II, were isolated
      from an Escherichia coli O157:H7 strain, Morioka V526, and their entire
      nucleotide sequences were determined. The genomes of both phages were similar
      except for the stx gene-flanking regions. Comparing these phages to other known
      Stx-converting phages, we concluded that Stx1 phi is a novel Stx1-converting
      phage closely related to Stx2-converting phages so far reported.

PMID- 12813093
TI  - The dinB operon and spontaneous mutation in Escherichia coli.
AB  - Apparently conflicting data regarding the role of SOS-inducible, error-prone DNA
      polymerase IV (DinB) in spontaneous mutation are resolved by the finding that
      mutation is reduced by a polar allele with which dinB and neighboring yafN are
      deleted but not by two nonpolar dinB alleles. We demonstrate the existence of a
      dinB operon that contains four genes, dinB-yafN-yafO-yafP. The results imply a
      role for yafN, yafO, and/or yafP in spontaneous mutation.

PMID- 12813096
TI  - Kay Redfield Jamison, PhD: from an unquiet mind to rational exuberance.

PMID- 12813094
TI  - Bradyrhizobium japonicum NnrR, a denitrification regulator, expands the FixLJ
      FixK2 regulatory cascade.
AB  - In Bradyrhizobium japonicum, a gene named nnrR was identified which encodes a
      protein with high similarity to FNR/CRP-type transcriptional regulators. Mutant
      strains carrying an nnrR null mutation were unable to grow anaerobically in the
      presence of nitrate or nitrite, and they lacked both nitrate and nitrite
      reductase activities. Anaerobic activation of an nnrR'-'lacZ fusion required
      FixLJ and FixK(2). In turn, N oxide-mediated induction of nir and nor genes
      encoding nitrite and nitric oxide reductase, respectively, depended on NnrR.
      Thus, NnrR expands the FixLJ-FixK(2) regulatory cascade by an additional control
      level which integrates the N oxide signal required for maximal induction of the
      denitrification genes.

PMID- 12813097
TI  - Online empathy for mood disorders: patients turn to internet support groups.

PMID- 12813095
TI  - The ATPase FliI can interact with the type III flagellar protein export apparatus
      in the absence of its regulator, FliH.
AB  - Salmonella FliI is the ATPase that drives flagellar protein export. It normally
      exists as a complex together with the regulatory protein FliH. A fliH null mutant
      was slightly motile, with overproduction of FliI resulting in substantial
      improvement of its motility. Mutations in the cytoplasmic domains of FlhA and
      FlhB, which are integral membrane components of the type III flagellar export
      apparatus, also resulted in substantially improved motility, even at normal FliI
      levels. Thus, FliH, though undoubtedly important, is not essential.

PMID- 12813098
TI  - Researchers probe depression in children.

PMID- 12813103
TI  - From the Centers for Disease Control and Prevention. Post-detention completion of
      tuberculosis treatment for persons deported or released from the custody of the
      Immigration and Naturalization Service--United States, 2003.

PMID- 12813104
TI  - Affirmative action in medical school admissions.

PMID- 12813105
TI  - Affirmative action in medical school admissions.

PMID- 12813106
TI  - Affirmative action in medical school admissions.

PMID- 12813107
TI  - Affirmative action in medical school admissions.

PMID- 12813108
TI  - Affirmative action in medical school admissions.

PMID- 12813109
TI  - Affirmative action in medical school admissions.

PMID- 12813110
TI  - Affirmative action in medical school admissions.

PMID- 12813111
TI  - Quality of care in profit vs not-for-profit dialysis centers.

PMID- 12813112
TI  - Quality of care in profit vs not-for-profit dialysis centers.

PMID- 12813113
TI  - Quality of care in profit vs not-for-profit dialysis centers.

PMID- 12813114
TI  - Quality of care in profit vs not-for-profit dialysis centers.

PMID- 12813115
TI  - The epidemiology of major depressive disorder: results from the National
      Comorbidity Survey Replication (NCS-R).
AB  - CONTEXT: Uncertainties exist about prevalence and correlates of major depressive
      disorder (MDD). OBJECTIVE: To present nationally representative data on
      prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates
      of treatment and treatment adequacy from the recently completed National
      Comorbidity Survey Replication (NCS-R). DESIGN: Face-to-face household survey
      conducted from February 2001 to December 2002. SETTING: The 48 contiguous United
      States. PARTICIPANTS: Household residents ages 18 years or older (N = 9090) who
      responded to the NCS-R survey. MAIN OUTCOME MEASURES: Prevalence and correlates
      of MDD using the World Health Organization's (WHO) Composite International
      Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of
      Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale
      (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews
      used the Structured Clinical Interview for DSM-IV. RESULTS: The prevalence of
      CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6
      35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2
      million US adults). Virtually all CIDI 12-month cases were independently
      classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6%
      moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks
      (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as
      indicated by 59.3% of 12-month cases with severe or very severe role impairment.
      Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV
      disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12
      month cases received health care treatment for MDD, treatment was adequate in
      only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1
      25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of
      treatment were far less numerous than those of prevalence. CONCLUSIONS: Major
      depressive disorder is a common disorder, widely distributed in the population,
      and usually associated with substantial symptom severity and role impairment.
      While the recent increase in treatment is encouraging, inadequate treatment is a
      serious concern. Emphasis on screening and expansion of treatment needs to be
      accompanied by a parallel emphasis on treatment quality improvement.

PMID- 12813116
TI  - Effects of treating depression and low perceived social support on clinical
      events after myocardial infarction: the Enhancing Recovery in Coronary Heart
      Disease Patients (ENRICHD) Randomized Trial.
AB  - CONTEXT: Depression and low perceived social support (LPSS) after myocardial
      infarction (MI) are associated with higher morbidity and mortality, but little is
      known about whether this excess risk can be reduced through treatment. OBJECTIVE:
      To determine whether mortality and recurrent infarction are reduced by treatment
      of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a
      selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in
      patients enrolled within 28 days after MI. DESIGN, SETTING, AND PATIENTS:
      Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI
      patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor
      depression was diagnosed by modified Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating
      Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in
      Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI).
      Random allocation was to usual medical care or CBT-based psychosocial
      intervention. INTERVENTION: Cognitive behavior therapy was initiated at a median
      of 17 days after the index MI for a median of 11 individual sessions throughout 6
      months, plus group therapy when feasible, with SSRIs for patients scoring higher
      than 24 on the HRSD or having a less than 50% reduction in Beck Depression
      Inventory scores after 5 weeks. MAIN OUTCOME MEASURES: Composite primary end
      point of death or recurrent MI; secondary outcomes included change in HRSD (for
      depression) or ESSI scores (for LPSS) at 6 months. RESULTS: Improvement in
      psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD
      score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4
      (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI
      score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in
      the LPSS and usual care group (P<.001). After an average follow-up of 29 months,
      there was no significant difference in event-free survival between usual care
      (75.9%) and psychosocial intervention (75.8%). There were also no differences in
      survival between the psychosocial intervention and usual care arms in any of the
      3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients).
      CONCLUSIONS: The intervention did not increase event-free survival. The
      intervention improved depression and social isolation, although the relative
      improvement in the psychosocial intervention group compared with the usual care
      group was less than expected due to substantial improvement in usual care
      patients.

PMID- 12813117
TI  - Group interpersonal psychotherapy for depression in rural Uganda: a randomized
      controlled trial.
AB  - CONTEXT: Despite the importance of mental illness in Africa, few controlled
      intervention trials related to this problem have been published. OBJECTIVES: To
      test the efficacy of group interpersonal psychotherapy in alleviating depression
      and dysfunction and to evaluate the feasibility of conducting controlled trials
      in Africa. DESIGN, SETTING, AND PARTICIPANTS: For this cluster randomized,
      controlled clinical trial (February-June 2002), 30 villages in the Masaka and
      Rakai districts of rural Uganda were selected using a random procedure; 15 were
      then randomly assigned for studying men and 15 for women. In each village, adult
      men or women believed by themselves and other villagers to have depressionlike
      illness were interviewed using a locally adapted Hopkins Symptom Checklist and an
      instrument assessing function. Based on these interviews, lists were created for
      each village totaling 341 men and women who met Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression or
      subsyndromal depression. Interviewers revisited them in order of decreasing
      symptom severity until they had 8 to 12 persons per village, totaling 284. Of
      these, 248 agreed to be in the trial and 9 refused; the remainder died or
      relocated. A total of 108 men and 116 women completed the study and were
      reinterviewed. INTERVENTION: Eight of the 15 male villages and 7 of the 15 female
      villages were randomly assigned to the intervention arm and the remainder to the
      control arm. The intervention villages received group interpersonal psychotherapy
      for depression as weekly 90-minute sessions for 16 weeks. MAIN OUTCOME MEASURES:
      Depression and dysfunction severity scores on scales adapted and validated for
      local use; proportion of persons meeting DSM-IV major depression diagnostic
      criteria. RESULTS: Mean reduction in depression severity was 17.47 points for
      intervention groups and 3.55 points for controls (P<.001). Mean reduction in
      dysfunction was 8.08 and 3.76 points, respectively (P<.001). After intervention,
      6.5% and 54.7% of the intervention and control groups, respectively, met the
      criteria for major depression (P<.001) compared with 86% and 94%, respectively,
      prior to intervention (P =.04). The odds of postintervention depression among
      controls was 17.31 (95% confidence interval, 7.63-39.27) compared with the odds
      among intervention groups. Results from intention-to-treat analyses remained
      statistically significant. CONCLUSIONS: Group interpersonal psychotherapy was
      highly efficacious in reducing depression and dysfunction. A clinical trial
      proved feasible in the local setting. Both findings should encourage similar
      trials in similar settings in Africa and beyond.

PMID- 12813118
TI  - Regional brain metabolic correlates of alpha-methylparatyrosine-induced
      depressive symptoms: implications for the neural circuitry of depression.
AB  - CONTEXT: We previously used positron emission tomography (PET) measurement of
      brain metabolism with 18fluorodeoxyglucose to show that patients receiving
      selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion
      induced return of depressive symptoms have an acute decrease in metabolism in
      orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients
      with depression in remission while taking norepinephrine reuptake inhibitors
      (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion
      of norepinephrine and dopamine using alpha-methylparatyrosine (AMPT). OBJECTIVE:
      To assess brain metabolic correlates of AMPT administration in patients with
      depression in remission while receiving NRIs. DESIGN, SETTING, AND PARTICIPANTS:
      Randomized, controlled, double-blind trial in which 18 patients recruited in 1997
      2000 from the general community who had depression in remission while taking NRIs
      had PET imaging in a psychiatric research unit following AMPT and placebo
      administration. INTERVENTIONS: After initial medication with desipramine and
      follow-up until response, patients underwent active AMPT (five 1-g doses
      administered orally over 28 hours) and placebo (diphenhydramine hydrochloride,
      five 50- mg doses administered similarly) catecholamine depletion challenges in
      randomized order of assignment, after which PET imaging was performed on day 3 of
      each condition. Both study conditions were performed 1 week apart. MAIN OUTCOME
      MEASURES: Regional brain metabolism rates in patients with and without AMPT
      induced return of depressive symptoms. RESULTS: AMPT-induced return of depressive
      symptoms was experienced by 11 of the 18 patients and led to decreased brain
      metabolism in a number of cortical areas, with the greatest magnitude of effects
      in orbitofrontal (P =.002) and dorsolateral prefrontal (P =.03) cortex and
      thalamus (P =.006). Increased resting metabolism in prefrontal and limbic areas
      predicted vulnerability to return of depressive symptoms. CONCLUSIONS: Different
      neurochemical systems that mediate depression may have effects on a common brain
      circuitry. Baseline metabolism in successfully treated depressed patients may
      predict vulnerability to future episodes of depression.

PMID- 12813119
TI  - Cost of lost productive work time among US workers with depression.
AB  - CONTEXT: Evidence consistently indicates that depression has adversely affected
      work productivity. Estimates of the cost impact in lost labor time in the US
      workforce, however, are scarce and dated. OBJECTIVE: To estimate the impact of
      depression on labor costs (ie, work absence and reduced performance while at
      work) in the US workforce. DESIGN, SETTING, AND PARTICIPANTS: All employed
      individuals who participated in the American Productivity Audit (conducted August
      1, 2001-July 31, 2002) between May 20 and July 11, 2002, were eligible for the
      Depressive Disorders Study. Those who responded affirmatively to 2 depression
      screening questions (n = 692), as well as a 1:4 stratified random sample of those
      responding in the negative (n = 435), were recruited for and completed a
      supplemental interview using the Primary Care Evaluation of Mental Disorders Mood
      Module for depression, the Somatic Symptom Inventory, and a medical and treatment
      history for depression. Excess lost productive time (LPT) costs from depression
      were derived as the difference in LPT among individuals with depression minus the
      expected LPT in the absence of depression projected to the US workforce. MAIN
      OUTCOME MEASURE: Estimated LPT and associated labor costs (work absence and
      reduced performance while at work) due to depression. RESULTS: Workers with
      depression reported significantly more total health-related LPT than those
      without depression (mean, 5.6 h/wk vs an expected 1.5 h/wk, respectively). Eighty
      one percent of the LPT costs are explained by reduced performance while at work.
      Major depression accounts for 48% of the LPT among those with depression, again
      with a majority of the cost explained by reduced performance while at work. Self
      reported use of antidepressants in the previous 12 months among those with
      depression was low (<33%) and the mean reported treatment effectiveness was only
      moderate. Extrapolation of these survey results and self-reported annual incomes
      to the population of US workers suggests that US workers with depression employed
      in the previous week cost employers an estimated 44 billion dollars per year in
      LPT, an excess of 31 billion dollars per year compared with peers without
      depression. This estimate does not include labor costs associated with short- and
      long-term disability. CONCLUSIONS: A majority of the LPT costs that employers
      face from employee depression is invisible and explained by reduced performance
      while at work. Use of treatments for depression appears to be relatively low. The
      combined LPT burden among those with depression and the low level of treatment
      suggests that there may be cost-effective opportunities for improving depression
      related outcomes in the US workforce.

PMID- 12813120
TI  - Educational and organizational interventions to improve the management of
      depression in primary care: a systematic review.
AB  - CONTEXT: Depression is commonly encountered in primary care settings yet is often
      missed or suboptimally managed. A number of organizational and educational
      strategies to improve management of depression have been proposed. The clinical
      effectiveness and cost-effectiveness of these strategies have not yet been
      subjected to systematic review. OBJECTIVE: To systematically evaluate the
      effectiveness of organizational and educational interventions to improve the
      management of depression in primary care settings. DATA SOURCES: We searched
      electronic medical and psychological databases from inception to March 2003
      (MEDLINE, PsycLIT, EMBASE, CINAHL, Cochrane Controlled Trials Register, United
      Kingdom National Health Service Economic Evaluations Database, Cochrane
      Depression Anxiety and Neurosis Group register, and Cochrane Effective
      Professional and Organisational Change Group specialist register); conducted
      correspondence with authors; and used reference lists. Search terms were related
      to depression, primary care, and all guidelines and organizational and
      educational interventions. STUDY SELECTION: We selected 36 studies, including 29
      randomized controlled trials and nonrandomized controlled clinical trials, 5
      controlled before-and-after studies, and 2 interrupted time-series studies.
      Outcomes relating to management and outcome of depression were sought. DATA
      EXTRACTION: Methodological details and outcomes were extracted and checked by 2
      reviewers. Summary relative risks were, where possible, calculated from original
      data and attempts were made to correct for unit of analysis error. DATA
      SYNTHESIS: A narrative synthesis was conducted. Twenty-one studies with positive
      results were found. Strategies effective in improving patient outcome generally
      were those with complex interventions that incorporated clinician education, an
      enhanced role of the nurse (nurse case management), and a greater degree of
      integration between primary and secondary care (consultation-liaison). Telephone
      medication counseling delivered by practice nurses or trained counselors was also
      effective. Simple guideline implementation and educational strategies were
      generally ineffective. CONCLUSIONS: There is substantial potential to improve the
      management of depression in primary care. Commonly used guidelines and
      educational strategies are likely to be ineffective. The implementation of the
      findings from this research will require substantial investment in primary care
      services and a major shift in the organization and provision of care.

PMID- 12813121
TI  - Past, present, and future directions for defining optimal treatment outcome in
      depression: remission and beyond.
AB  - During the past decade, evidence from research on mood disorders has demonstrated
      that remission is the optimal outcome of treatment. However, there continues to
      be considerable variability in the specific characteristics that are accepted as
      indicators of remission. Increasing knowledge of mood disorders and their
      underlying mechanisms may allow for the development of a new diagnostic and
      assessment system that no longer is based solely on symptoms and other
      descriptive phenomena. Continued advances in neuroscience may allow for more
      knowledge of the underlying neurobiological status and more accurate assessments
      of the underlying disease state and response to treatment, thus enabling
      physicians to use treatments that will most effectively bring patients back to
      euthymia and a truly disease-free healthy state. Until then, remission should
      continue to be based on the descriptive and experiential phenomena of symptoms
      and psychosocial functioning.

PMID- 12813122
TI  - Confronting depression and suicide in physicians: a consensus statement.
AB  - OBJECTIVE: To encourage treatment of depression and prevention of suicide in
      physicians by calling for a shift in professional attitudes and institutional
      policies to support physicians seeking help. PARTICIPANTS: An American Foundation
      for Suicide Prevention planning group invited 15 experts on the subject to
      evaluate the state of knowledge about physician depression and suicide and
      barriers to treatment. The group assembled for a workshop held October 6-7, 2002,
      in Philadelphia, Pa. EVIDENCE: The planning group worked with each participant on
      a preworkshop literature review in an assigned area. Abstracts of presentations
      and key publications were distributed to participants before the workshop. After
      workshop presentations, participants were assigned to 1 of 2 breakout groups: (1)
      physicians in their role as patients and (2) medical institutions and
      professional organizations. The groups identified areas that required further
      research, barriers to treatment, and recommendations for reform. CONSENSUS
      PROCESS: This consensus statement emerged from a plenary session during which
      each work group presented its recommendations. The consensus statement was
      circulated to and approved by all participants. CONCLUSIONS: The culture of
      medicine accords low priority to physician mental health despite evidence of
      untreated mood disorders and an increased burden of suicide. Barriers to
      physicians' seeking help are often punitive, including discrimination in medical
      licensing, hospital privileges, and professional advancement. This consensus
      statement recommends transforming professional attitudes and changing
      institutional policies to encourage physicians to seek help. As barriers are
      removed and physicians confront depression and suicidality in their peers, they
      are more likely to recognize and treat these conditions in patients, including
      colleagues and medical students.

PMID- 12813123
TI  - Research on major depression: strategies and priorities.

PMID- 12813124
TI  - Awareness about depression: important for all physicians.

PMID- 12813125
TI  - Depression--a cardiac risk factor in search of a treatment.

PMID- 12813126
TI  - JAMA patient page. Depression.

PMID- 12813127
TI  - A mechanism of covalent substrate binding in the x-ray structure of subunit K of
      the Escherichia coli dihydroxyacetone kinase.
AB  - Dihydroxyacetone (Dha) kinases are homologous proteins that use different
      phosphoryl donors, a multiphosphoryl protein of the phosphoenolpyruvate-dependent
      carbohydrate:phosphotransferase system in bacteria, ATP in animals, plants, and
      some bacteria. The Dha kinase of Escherichia coli consists of three subunits,
      DhaK and DhaL, which are colinear to the ATP-dependent Dha kinases of eukaryotes,
      and the multiphosphoryl protein DhaM. Here we show the crystal structure of the
      DhaK subunit in complex with Dha at 1.75 A resolution. DhaK is a homodimer with a
      fold consisting of two six-stranded mixed beta-sheets surrounded by nine alpha
      helices and a beta-ribbon covering the exposed edge strand of one sheet. The core
      of the N-terminal domain has an alpha/beta fold common to subunits of
      carbohydrate transporters and transcription regulators of the phosphoenolpyruvate
      dependent carbohydrate:phosphotransferase system. The core of the C-terminal
      domain has a fold similar to the C-terminal domain of the cell-division protein
      FtsZ. A molecule of Dha is covalently bound in hemiaminal linkage to the N
      epsilon 2 of His-230. The hemiaminal does not participate in covalent catalysis
      but is the chemical basis for discrimination between short-chain carbonyl
      compounds and polyols. Paralogs of Dha kinases occur in association with
      transcription regulators of the TetR/QacR and the SorC families, pointing to
      their biological role as sensors in signaling.

PMID- 12813128
TI  - Relation of PvuII site polymorphism in the COL1A2 gene to the risk of fractures
      in prepubertal Finnish girls.
AB  - Genetic susceptibility to fractures may be detectable in early childhood. We
      evaluated the associations between the polymorphic PvuII site of the COL1A2 gene
      and bone properties assessed by different modalities (dual-energy X-ray
      absorptiometry; peripheral quantitative computed tomography; gel coupling
      scanning quantitative ultrasonometry; ultrasound bone sonometry), bone turnover
      markers, and the occurrence of fractures in 244 prepubertal Finnish girls. Tanner
      stage and physical characteristics did not differ significantly among girls with
      different COL1A2 genotypes. The polymorphism was not significantly associated
      with different bone properties or any of the bone turnover markers when girls at
      Tanner stage I (prepuberty) and stage II (early puberty) were considered
      together, but there was a significant association with spine bone mineral content
      (BMC) and bone mineral density (BMD), as well as with speed of sound (SOS) (P <
      0.05), when girls at Tanner stage I were considered separately, as a purpose to
      avoid the confounding effect that the pubertal growth spurt has on skeletal
      development. The distribution of fractures was different between the three
      genotype groups (P = 0.023). The P alleles were over-represented in girls who had
      been fractured at least once; 88% of them had at least one copy of the P allele
      (either PP or Pp). Girls with the PP genotype had 4.9 times higher relative risk
      for fractures than girls with the pp genotype (95% CI, 1.4 to 17.4; P = 0.015).
      No significant difference was found between fractured and nonfractured girls in
      anthropometric measurements, physical activity, or bone mass. However, BMD of the
      spine and SOS at the radius and tibia were significantly lower in the fractured
      girls. We conclude that the COL1A2 polymorphism is associated with
      nonosteoporotic fractures in prepubertal girls independently of bone density.

PMID- 12813129
TI  - Reduction of beta-catenin/T-cell transcription factor signaling by aspirin and
      indomethacin is caused by an increased stabilization of phosphorylated beta
      catenin.
AB  - Constitutive activation of the Wnt/beta-catenin pathway is thought to play a
      central role in colorectal carcinogenesis. A key output in this pathway is the
      nuclear level of beta-catenin, which determines the transcription of T-cell
      transcription factor (TCF)/lymphoid enhancer-binding factor-responsive target
      genes. In unstimulated cells, beta-catenin is continuously targeted for ubiquitin
      dependent degradation, which depends on its NH(2)-terminal phosphorylation by
      glycogen synthase kinase-3beta (GSK-3beta) in association with a multiprotein
      complex. Previously, we have shown that the nonsteroidal anti-inflammatory drugs
      (NSAIDs) aspirin and indomethacin down-regulate beta-catenin/TCF signaling in
      colorectal cancer cells. Here, we demonstrate that the reduced signaling activity
      of beta-catenin in response to NSAIDs is a result of its enhanced
      phosphorylation. In SW948 and SW480 colorectal cancer cells, phosphorylation of
      NH(2)-terminal S/T residues time dependently increased in response to aspirin and
      indomethacin. In contrast, in 293 cells, NSAID treatment failed to induce
      detectable levels of beta-catenin phosphorylation but resulted in degradation of
      beta-catenin within 24 h in serum-deprived cells. The aspirin-induced beta
      catenin phosphorylation in colon cancer cells preceded down-regulation of beta
      catenin/TCF signaling, suggesting a causal relationship. Inhibition of this
      process by LiCl pointed to participation of GSK-3beta. Unexpectedly, GSK-3beta
      was also phosphorylated upon aspirin treatment in six colorectal cancer cell
      lines. We present evidence that inactivation of a phosphatase rather than
      stimulation of a kinase or interference with the ubiquitination machinery may be
      the cause of the stabilized phosphorylation. The data emphasize the importance of
      beta-catenin in the pathogenesis of colorectal cancer and define it as a key
      target for anticancer therapeutics.

PMID- 12813130
TI  - Characterization of the cytotoxic activities of novel analogues of the antitumor
      agent, lavendamycin.
AB  - Lavendamycin is a bacterially derived quinolinedione that displays significant
      antimicrobial and antitumor activities. However, preclinical development of
      lavendamycin as an anticancer agent was halted due to the poor aqueous solubility
      and relatively nonspecific cytotoxic activity of this compound. In this report,
      we have examined the cytotoxic activities of a series of novel lavendamycin
      analogues. The cytotoxic activities of these compounds were evaluated in
      clonogenic survival assays with A549 lung carcinoma cells. Compounds bearing an
      amide or amine substituent at the R(3) position were the most potent inhibitors
      of colony formation. MB-97, the most active member of this subgroup, decreased
      clonogenic outgrowth by 70% at a concentration of 10 n. Treatment of A549 cells
      with MB-97 led to an increase in p53 protein expression and phosphorylation and a
      concomitant increase in the expression of the p53 target gene, p21. Exposure of
      p53-positive cells to MB-97 triggered cell cycle arrest in G(1) and G(2) phases
      but induced a selective G(2)-phase arrest in p53-negative cells. MB-97 treatment
      also induced a higher level of apoptosis in p53-null cells relative to their p53
      positive counterparts. Finally, MB-97 showed significant cytotoxic activity in
      the National Cancer Institute's panel of 60 cancer cell lines and antitumor
      activity in vivo in hollow fiber tumorigenesis assays.

PMID- 12813131
TI  - Cytochrome P450 1B1 (CYP1B1) is overexpressed in human colon adenocarcinomas
      relative to normal colon: implications for drug development.
AB  - The cytochrome P450 family of enzymes is involved in the Phase I metabolism of a
      wide variety of compounds. Although generally involved with detoxification,
      overexpression of one family member, cytochrome P450 1B1 (CYP1B1), has been
      associated with human epithelial tumors. As such, CYP1B1 was hypothesized to be a
      novel target for the development of anticancer therapies. We investigated
      expression of CYP1B1 protein in 61 human colorectal adenocarcinomas and compared
      this to that observed in 14 histologically normal human large bowel samples
      removed from patients undergoing surgery for large bowel tumors. Although we
      confirmed that CYP1B1 was expressed at high levels in human colorectal tumor
      epithelia, we also found that CYP1B1 was not absent from normal colonic epithelia
      but was expressed at low levels. The expression of CYP1B1 in colon tumors does
      not correlate with tumor stage or degree of lymph node invasion in this study.
      Furthermore, in addition to expression in colon epithelia, CYP1B1 is also
      observed in blood vessels within the colon. As with the epithelia, levels of
      CYP1B1 were higher in tumor vasculature than that of the normal colon. Although
      these observations greatly support the development of CYP1B1 targeted anticancer
      therapies, they also indicate the caution that should be observed when developing
      such drugs.

PMID- 12813132
TI  - mRNA expression levels of E2F transcription factors correlate with dihydrofolate
      reductase, reduced folate carrier, and thymidylate synthase mRNA expression in
      osteosarcoma.
AB  - Previous studies have shown that decreased expression of the reduced folate
      carrier (RFC) and increased expression of dihydrofolate reductase (DHFR) are
      associated with intrinsic and acquired methotrexate resistance, respectively, in
      osteosarcoma (OS). It has also been shown in colorectal cancer that E2F-1
      expression correlates with thymidylate synthase (TS) and, to a lesser extent,
      DHFR expression. To begin to investigate the regulation of DHFR and RFC
      expression in OS samples, mRNA expression of E2F-1 and E2F-4 were measured in OS
      tumor samples and related to DHFR, RFC, and TS mRNA expression. Using fluorescent
      quantitative real-time PCR, 112 human OS patient samples were investigated for
      potential E2F-1/E2F-4:DHFR, E2F-1/E2F-4:RFC, and E2F-1/E2F-4:TS correlations. The
      expression ranges for each gene are as follows: DHFR, 0.02-33.13 (median = 0.20);
      RFC, 0.02-229.13 (median = 1.91); TS, 0.01-9.99 (median = 0.15); E2F-1, 0.05
      69.07 (median = 0.52); and E2F-4, 0.24-52.35 (median = 1.45). Spearman
      correlation coefficients (r(s)) for E2F-1:DHFR, E2F-1:RFC, E2F-1:TS, E2F-4:DHFR,
      E2F-4:RFC, and E2F-4:TS were calculated to be 0.53, 0.63, 0.60, 0.41, 0.58, and
      0.33, respectively (P < 0.001). On the basis of this data, moderate correlations
      exist between E2F-1/E2F-4 and DHFR, RFC, and TS. These results suggest E2F-1/E2F
      4 may play a role in the regulation of RFC expression, which has not been
      reported previously. The E2F transcription factors are also related to DHFR and
      TS expression in OS samples, suggesting a possible involvement in methotrexate
      resistance. Although E2F mRNA levels correlate with DHFR, RFC, and TS mRNA
      expression, additional experiments are necessary to determine the direct effects
      of these transcription factors and identify other proteins that may influence
      this relationship.

PMID- 12813133
TI  - Human Chk1 expression is dispensable for somatic cell death and critical for
      sustaining G2 DNA damage checkpoint.
AB  - Mammalian Chk1 is an essential kinase for embryonic development and plays an
      important role in the cellular response to DNA damage. However, it remains
      unclear whether inhibition of Chk1 induces apoptosis in somatic cells. The
      uncertainty has become a critical issue for rationale design of Chk1 mechanism
      based anticancer drugs. Here we show that Chk1 small interfering RNA (siRNA)
      effectively eliminates Chk1 protein expression without altering the cell cycle
      profile or inducing apoptosis in various human cancer cell lines under normal
      conditions. In the presence of DNA-damaging agents, however, Chk1 siRNA alone is
      sufficient to abrogate the DNA damage-induced G(2) checkpoint and significantly
      enhance apoptosis. Cell cycle kinetic profiles show that abrogation of G(2)
      arrest is mediated through shortening of the checkpoint. We also demonstrate that
      Chk1 siRNA enhances DNA damage-induced apoptosis in p53-deficient cancer cell
      lines and augments the growth inhibition conferred by DNA-damaging agents. These
      findings imply that Chk1 inhibitors will have low cytotoxicity on their own and
      can enhance the efficacy of DNA-damaging drugs.

PMID- 12813135
TI  - ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor,
      shows antimetastatic activity using a hepatocellular carcinoma model.
AB  - The epidermal growth factor receptor (EGFR) is highly expressed in many human
      tumors and provides a new target for anticancer drug development. EGFR-targeted
      agents have shown promising antitumor activity in preclinical and clinical
      trials. However, little is yet known about the effect of these new agents on
      tumor metastasis. Here, we investigate the effects of ZD1839 (Iressa), a
      selective EGFR tyrosine kinase inhibitor, on the metastatic properties of murine
      hepatocellular carcinoma CBO140C12. ZD1839 inhibited not only cell growth but
      also epidermal growth factor-induced chemotactic migration and production of
      active matrix metalloproteinase-9 in vitro. In mice, orthotopic implantation of a
      fragment of CBO140C12 tumor into the liver resulted in the formation of a
      solitary tumor nodule and intrahepatic metastasis. ZD1839, given p.o., inhibited
      growth of the implanted tumor and intrahepatic metastasis by approximately 50%.
      These results indicate that EGFR signaling plays an important role in tumor
      metastasis and that ZD1839 is effective at inhibiting intrahepatic metastasis.

PMID- 12813134
TI  - Flavopiridol enhances the effect of docetaxel in vitro and in vivo in human
      gastric cancer cells.
AB  - Gastric cancer is one of the leading causes of cancer death throughout the world.
      It is a disease in desperate need of new therapeutic approaches. Docetaxel, a
      semisynthetic taxane, has shown potent activity against a broad range of solid
      tumors. However, in gastric cancer, response rates to docetaxel remain only
      approximately 20%. In these studies we show that flavopiridol, a cyclin-dependent
      kinase inhibitor, potentiates docetaxel-induced apoptosis 3-fold in MKN-74 human
      gastric cells. This effect is sequence dependent, such that flavopiridol must
      follow docetaxel to induce this effect. Docetaxel induces transient arrest in the
      M phase of the cell cycle. Cells exit mitosis in a specific time window without
      cytokinesis with a decrease in cyclin B1/cdc-2 kinase activity and MPM-2
      labeling. Flavopiridol treatment of docetaxel-treated cells enhances the exit
      from mitosis with a more rapid decrease in mitotic markers including MPM-2
      labeling and cyclin B1/cdc2 kinase activity. In contrast, pretreatment with
      flavopiridol prevents cells from entering mitosis by inhibiting cyclin B1/cdc-2
      kinase activity, thus antagonizing the docetaxel effect. The testing of this
      combination against MKN-74 xenografts confirms the sequence dependency. Treatment
      of MKN-74 tumor-bearing xenografts with docetaxel at a dose of 10 mg/kg followed
      3-7 h later by flavopiridol at a dose of 2.5 mg/kg resulted in a 1-18% decrease
      in tumor volume. In contrast, treatment with docetaxel alone at this same dose
      resulted in a 394% increase in tumor volume. When flavopiridol was given
      immediately after docetaxel, the effect was not statistically different from that
      of docetaxel alone. The reverse combination of flavopiridol followed 7 h later by
      docetaxel was similar to treatment with docetaxel alone. Flavopiridol alone had
      no effect in this tumor model. Thus, flavopiridol, when combined with docetaxel
      in a sequence-specific manner, may provide a completely new therapeutic approach
      in the treatment of gastric cancer.

PMID- 12813136
TI  - Cytoreductive effects of farnesyl transferase inhibitors on multiple myeloma
      tumor cells.
AB  - Farnesyl transferase inhibitors (FTIs) are anticancer agents designed to target
      ras processing and ras-dependent signal pathways. Because oncogenic ras mutations
      are found in up to 50% of multiple myeloma (MM) specimens, these agents may be
      effective in this disease. However, some preclinical studies suggest that FTI
      antitumor responses are unrelated to effects on ras. To address this issue in
      myeloma, we used the ANBL-6 myeloma cell line where interleukin (IL)-6-dependent
      cells are stably transfected with mutated N-ras or K-ras genes. Because
      expression of mutated ras allows for IL-6-independent growth, this is a good
      model to test whether FTIs specifically target growth-promoting ras-activated
      pathways in myeloma. Although they had little effect in 10% serum, two separate
      FTIs induced apoptosis of myeloma cells when cultured in low serum, and mutated
      ras-expressing cells were more sensitive than wild-type (WT) ras-expressing
      cells. However, induction of apoptosis did not correlate with inhibition of ras
      processing. Although they had no effect on AKT activity, under low serum
      conditions FTIs inhibited constitutive activation of the p70S6kinase and nuclear
      factor kappaB signal proteins in both mutated ras-expressing MM lines and
      extracellular signal-regulated kinase (ERK) activity in mutated N-ras-expressing
      cells. However, in studies where p70, nuclear factor kappaB, and ERK were
      comparably inhibited by other inhibitors or by gene transfer, we could not
      identify effects on these pathways as participating in the apoptotic response.
      FTIs were also able to abrogate the IL-6 proliferative response of WT ras
      expressing MM cells, and this was associated with inhibition of IL-6-induced
      activation of ERK, AKT, and p70. The induction of apoptosis and prevention of the
      IL-6 response in MM cells containing mutated or WT ras provide support for the
      therapeutic potential of FTIs in this disease.

PMID- 12813137
TI  - Why target apoptosis in cancer treatment?
AB  - Defective apoptosis (programmed cell death) represents a major causative factor
      in the development and progression of cancer. The ability of tumor cells to evade
      engagement of apoptosis can play a significant role in their resistance to
      conventional therapeutic regimens. Our understanding of the complexities of
      apoptosis and the mechanisms evolved by tumor cells to resist engagement of cell
      death has focused research effort into the development of strategies designed to
      selectively induce apoptosis in cancer cells. This article will review the
      underlying mechanisms of apoptosis and the ways in which tumor cells modulate
      these processes to promote their survival and evaluate the efficacy of current
      clinical approaches aimed at exploiting these defects to selectively induce
      apoptosis in tumor cells.

PMID- 12813138
TI  - Evaluation of cancer therapy using diffusion magnetic resonance imaging.
AB  - Assessment of the effectiveness of cancer therapy traditionally relies on
      comparison of tumor images acquired before and after therapeutic intervention by
      inspection of gross anatomical images to evaluate changes in tumor size. The
      potential for imaging to provide additional insights related to the therapeutic
      impact would be enhanced if a specific parameter or combination of parameters
      could be identified that reflect tissue changes at the cellular or physiological
      level. This information could also provide a more sensitive and earlier indicator
      of treatment response in an individual animal or patient. Diffusion magnetic
      resonance imaging can detect relatively small changes in tissue structure at the
      cellular level and thus provides an opportunity to quantitatively and serially
      follow therapeutic-induced changes in solid tumors. This article provides an
      overview of the use of diffusion magnetic resonance imaging as a surrogate marker
      for quantitating treatment responsiveness in both preclinical and clinical
      studies.

PMID- 12813139
TI  - Targeting Aurora-2 kinase in cancer.
AB  - Aurora-2 kinase has been shown to contribute to oncogenic transformation and is
      frequently overexpressed and amplified in many human tumor types. Aurora-2
      belongs to a small family of mitotic serine/threonine kinases that regulate
      centrosome maturation, chromosome segregation, and cytokinesis. The mechanism
      behind the transforming activity of aurora-2 is not fully understood; however,
      the role of aurora-2 in regulating the centrosome cycle is likely responsible for
      its ability to transform cells. Aurora-2 overexpression has been correlated with
      centrosome amplification, which can be a driving cause of genomic instability in
      tumor cells. In addition, recent work has demonstrated that aurora-2 plays an
      active function in promoting entry into mitosis by regulating local translation
      of centrosomal stored mRNA, such as cyclin B1. These recent findings implicate
      aurora-2 as an important regulator of both genomic integrity and cell cycle
      progression in cancer cells and suggest that aurora-2 is an attractive target for
      anticancer drug development.

PMID- 12813140
TI  - Tumor markers: from laboratory to clinical utility.

PMID- 12813141
TI  - Transient compartmentalization of interneuron dendrites.

PMID- 12813142
TI  - Nociception attenuates parasympathetic but not sympathetic baroreflex via NK1
      receptors in the rat nucleus tractus solitarii.
AB  - Somatic noxious stimulation can evoke profound cardiovascular responses by
      altering activity in the autonomic nervous system. This noxious stimulation
      attenuates the cardiac vagal baroreflex, a key cardiovascular homeostatic reflex.
      This attenuation is mediated via NK1 receptors expressed on GABAergic
      interneurones within the nucleus of the solitary tract (NTS). We have
      investigated the effect of noxious stimulation and exogenous substance P (SP) on
      the sympathetic component of the baroreflex. We recorded from the sympathetic
      chain in a decerebrate, artificially perfused rat preparation. Noxious hindlimb
      pinch was without effect on the sympathetic baroreflex although the cardiac vagal
      baroreflex gain was decreased (56 %, P < 0.01). Bilateral NTS microinjection of
      SP (500 fmol) produced a similar selective attenuation of the cardiac vagal
      baroreflex gain (62 %, P < 0.005) without effect on the sympathetic baroreflex.
      Recordings from the cardiac sympathetic and vagal nerves confirmed the
      selectivity of the SP inhibition. Control experiments using a GABAA receptor
      agonist, isoguvacine, indicated that both components of the baroreflex
      (parasympathetic and sympathetic) could be blocked from the NTS injection site.
      The NTS microinjection of a NK1 antagonist (CP-99,994) in vivo attenuated the
      tachycardic response to hindlimb pinch. Our data suggest that noxious pinch
      releases SP within the NTS to selectively attenuate the cardiac vagal, but not
      the sympathetic, component of the baroreflex. This selective withdrawal of the
      cardiac vagal baroreflex seems to underlie the pinch-evoked tachycardia seen in
      vivo. Further, these findings confirm that baroreflex sympathetic and
      parasympathetic pathways diverge, and can be independently controlled, within the
      NTS.

PMID- 12813143
TI  - Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in
      connective tissue during mechanical loading in humans.
AB  - Mechanical loading is known to increase connective tissue blood flow of human
      tendons and to cause local release of vasodilatory substances. The present study
      investigated the importance of prostaglandins (PG) formed by cyclo-oxygenase
      isoforms (COX-1 and 2) for the exercise-related increase in blood flow in
      connective tissue. Healthy individuals (n = 24, age: 23-31 years) underwent 30
      min of intermittent, isometric, plantarflexion with both calf muscles either
      without (n = 6, Control, C) or with blockade of PG formation, either COX-2
      specific (n = 10, Celecoxib 2 x 100 mg day-1 for 3 days prior to the experiment)
      or COX unspecific (n = 8, indomethacin 100 mg (12 and 1 h pre-experiment) and
      acetyl salicylic acid 500 mg day-1 for 3 days pre-experiment). Prostaglandin E2
      (PGE2) concentration was determined by microdialysis and blood flow by 133Xe
      washout. In C, interstitial PGE2 rose from (0.8 +/- 0.2 (rest) to 1.4 +/- 0.5 ng
      ml-1 (exercise), P < 0.05), whereas during unspecific COX inhibition, tissue PGE2
      was completely inhibited at rest and during exercise. COX-2 specific blockade did
      not inhibit tissue PGE2 at rest, but totally abolished the exercise induced
      increase. Blood flow was similar in the three groups at rest (P > 0.05), whereas
      the increase in flow with exercise was reduced by 35 and 43 % with COX-2 specific
      blockade (3.2 +/- 0.7 to 6.1 +/- 1.5 ml (100 g tissue)-1 min-1 or COX unspecific
      blockade (3.0 +/- 0.8 to 7.6 +/- 1.6), respectively, compared to C (2.7 +/- 0.8
      to 10.2 +/- 2.0)(P < 0.05). The findings indicate that COX-2 specific mechanisms
      are responsible for the exercise-induced increase in prostaglandin synthesis, and
      that increase in tissue prostaglandin plays an important role for blood flow in
      peritendinous connective tissue during physical loading in vivo.

PMID- 12813144
TI  - Carotid baroreflex responsiveness to head-up tilt-induced central hypovolaemia:
      effect of aerobic fitness.
AB  - This investigation examined the interaction between carotid baroreflex (CBR)
      responsiveness during head-up tilt (HUT)-induced central hypovolaemia and aerobic
      fitness. Seven average fit (AF) individuals, with a mean maximal oxygen uptake
      (VO2max) of 49 +/- 1 (ml O2) kg-1 min-1, and seven high fit (HF) individuals,
      with a VO2max of 61 +/- 1 (ml O2) kg-1 min-1, voluntarily participated in the
      investigation. After 10-15 min supine, each subject was exposed to nine levels of
      progressively increasing HUT by 10 deg increments from -20 deg to +60 deg. During
      the final 3 min of each stage of HUT, the CBR responsiveness was measured using a
      rapid pulse (500 ms) train of neck pressure (NP) and neck suction (NS) ranging
      from +40 to -80 Torr. The maximal gain of the carotid-HR (Gmax-HR) and carotid
      MAP (Gmax-MAP) baroreflex function curves was identified as measures of CBR
      responsiveness. During HUT-induced decreases in thoracic admittance, an index of
      central blood volume (CBV), the Gmax-HR and Gmax-MAP of the AF subjects increased
      more than the Gmax-HR and Gmax-MAP of the HF subjects (P < 0.05). The data
      demonstrate that the increase in the CBR responsiveness during a tilt-induced
      progressive unloading of the cardiopulmonary baroreceptors was attenuated in
      endurance-trained subjects. These findings provide an explanation for the
      predisposition to orthostatic hypotension and intolerance in well-trained
      athletes.

PMID- 12813145
TI  - Urinary bladder instability induced by selective suppression of the murine small
      conductance calcium-activated potassium (SK3) channel.
AB  - Small conductance, calcium-activated potassium (SK) channels have an important
      role in determining the excitability and contractility of urinary bladder smooth
      muscle. Here, the role of the SK isoform SK3 was examined by altering expression
      levels of the SK3 gene using a mouse model that conditionally overexpresses SK3
      channels (SK3T/T). Prominent SK3 immunostaining was found in both the smooth
      muscle (detrusor) and urothelium layers of the urinary bladder. SK currents were
      elevated 2.4-fold in isolated myocytes from SK3T/T mice. Selective suppression of
      SK3 expression by dietary doxycycline (DOX) decreased SK current density in
      isolated myocytes, increased phasic contractions of isolated urinary bladder
      smooth muscle strips and exposed high affinity effects of the blocker apamin of
      the SK isoforms (SK1-3), suggesting an additional participation from SK2
      channels. The role of SK3 channels in urinary bladder function was assessed using
      cystometry in conscious, freely moving mice. The urinary bladders of SK3T/T had
      significantly greater bladder capacity, and urine output exceeded the infused
      saline volume. Suppression of SK3 channel expression did not alter filling
      pressure, threshold pressure or bladder capacity, but micturition pressure was
      elevated compared to control mice. However, SK3 suppression did eliminate excess
      urine production and caused a marked increase in non-voiding contractions. The
      ability to examine bladder function in mice in which SK3 channel expression is
      selectively altered reveals that these channels have a significant role in the
      control of non-voiding contractions in vivo. Activation of these channels may be
      a therapeutic approach for management of non-voiding contractions, a condition
      which characterizes many types of urinary bladder dysfunctions including urinary
      incontinence.

PMID- 12813146
TI  - Number and spatial distribution of nuclei in the muscle fibres of normal mice
      studied in vivo.
AB  - We present here a new technique with which to visualize nuclei in living muscle
      fibres in the intact animal, involving injection of labelled DNA into single
      cells. This approach allowed us to determine the position of all of nuclei within
      a sarcolemma without labelling satellite cells. In contrast to what has been
      reported in tissue culture, we found that the nuclei were immobile, even when
      observed over several days. Nucleic density was uniform along the fibre except
      for the endplate and some myotendinous junctions, where the density was higher.
      The perijunctional region had the same number of nuclei as the rest of the fibre.
      In the extensor digitorum longus (EDL) muscle, the extrajunctional nuclei were
      elongated and precisely aligned to the long axis of the fibre. In the soleus, the
      nuclei were rounder and not well aligned. When comparing small and large fibres
      in the soleus, the number of nuclei varied approximately in proportion to
      cytoplasmic volume, while in the EDL the number was proportional to surface area.
      Statistical analysis revealed that the nuclei were not randomly distributed in
      either the EDL or the soleus. For each fibre, actual distributions were compared
      with computer simulations in which nuclei were assumed to repel each other, which
      optimizes the distribution of nuclei with respect to minimizing transport
      distances. The simulated patterns were regular, with clear row-like structures
      when the density of nuclei was low. The non-random and often row-like
      distribution of nuclei observed in muscle fibres may thus reflect regulatory
      mechanisms whereby nuclei repel each other in order to minimize transport
      distances.

PMID- 12813147
TI  - Pyramidal cell communication within local networks in layer 2/3 of rat neocortex.
AB  - The extent to which neocortical pyramidal cells function as a local network is
      determined by the strength and probability of their connections. By mapping
      connections between pyramidal cells we show here that in a local network of about
      600 pyramidal cells located within a cylindrical volume of 200 microm x 200
      microm of neocortical layer 2/3, an individual pyramidal cell receives synaptic
      inputs from about 30 other pyramidal neurons, with the majority of EPSP
      amplitudes in the 0.2-1.0 mV range. The probability of connection decreased from
      0.09 to 0.01 with intercell distance (over the range 25-200 microm). Within the
      same volume, local interneuron (fast-spiking non-accommodating interneuron, FS)
      pyramidal cell connections were about 10 times more numerous, with the majority
      of connections being reciprocal. The probability of excitatory and inhibitory
      connections between pyramidal cells and FS interneurons decreased only slightly
      with distance, being in the range 0.5-0.75. Pyramidal cells in the local network
      received strong synaptic input during stimulation of afferent fibres in layers 1
      and 6. Minimal-like stimulation of layer 1 or layer 6 inputs simultaneously
      induced postsynaptic potentials in connected pyramidal cells as well as in
      pyramidal-FS cell pairs. These inputs readily induced firing of pyramidal cells,
      although synaptically connected cells displayed different firing patterns.
      Unitary EPSPs in pyramidal-pyramidal cell pairs did not detectably alter cell
      firing. FS interneurons fire simultaneously with pyramidal cells. In pyramidal-FS
      cell pairs, both unitary EPSPs and IPSPs efficiently modulated cell firing
      patterns. We suggest that computation in the local network may proceed not only
      by direct pyramidal-pyramidal cell communication but also via local interneurons.
      With such a high degree of connectivity with surrounding pyramidal cells, local
      interneurons are ideally poised to both coordinate and expand the local pyramidal
      cell network via pyramidal-interneuron-pyramidal communication.

PMID- 12813148
TI  - A mechanical stretch induces contractile activation in unstimulated developing
      rat skeletal muscle in vitro.
AB  - The effects of a stretch-release cycle (approximately 25% of the resting muscle
      fibre length, Lo) on both tension and [Ca2+]i in small, unstimulated, intact
      muscle fibre bundles isolated from adult and neonatal rats were investigated at
      20 degrees C. The results show that the effects of the length change depended on
      the age of the rats. Thus, the length change produced three effects in the
      neonatal rat muscle fibre bundles, but only a single effect in the adult ones. In
      the neonatal fibre bundles, the length change led to an increase in resting
      muscle tension and to a transient increase in [Ca2+]i. The stretch-release cycle
      was then followed by a twitch-like tension response. In the adult fibre bundles,
      only the increase in resting tension was seen and both the transient increase in
      [Ca2+]i and the stretch-induced twitch-like tension response were absent. The
      amplitude of the twitch-like tension response was affected by both 2,3
      butanedione monoxime and sarcomere length in the same manner as active twitch
      tension, suggesting that it arose from actively cycling crossbridges. It was also
      reversibly abolished by 25 mM K+, 1 microM tetrodotoxin and 1.5 mM lidocaine
      (lignocaine), and was significantly depressed (P < 0.001) by lowering [Ca2+]o.
      These findings suggest that a rapid stretch in neonatal rats induces a propagated
      impulse that leads to an increase in [Ca2+]i, and that abolishing the action
      potential abolishes the stretch-induced twitch-like tension response. In 5- to 7
      day-old rats, the twitch-like tension response was approximately 50 % of the
      isometric twitch. It then decreased progressively with age and was virtually
      absent by the time the rats were 21 days old. Interestingly, this is the same
      period over which rat muscles differentiate from their neonatal to their adult
      types.

PMID- 12813149
TI  - Role of intrinsic nitrergic neurones on vagally mediated striated muscle
      contractions in the hamster oesophagus.
AB  - Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic
      neurones have been identified in the striated muscle oesophagus. However, the
      effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal
      striated muscles has not been defined. The present study was designed to
      investigate the role of intrinsic neurones on vagally evoked contractions of
      oesophageal striated muscles, using hamster oesophageal strips maintained in an
      organ bath. Stimulation (30 micros, 20 V) of the vagus nerve trunk produced
      twitch contractions. Piperine inhibited vagally evoked contractions, while
      capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory
      effect of piperine. The effect of L-NAME was reversed by subsequent addition of L
      arginine, but not by D-arginine. L-NAME did not have any effect on the vagally
      mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor,
      and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally
      evoked contractions by piperine and NONOate was fully reversed by ODQ, an
      inhibitor of guanylate cyclase. Immunohistochemical staining showed
      immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres
      in the myenteric plexus and the presence of choline acetyltransferase and NOS in
      the motor endplates. Only a few NOS-immunoreactive portions in the myenteric
      plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest
      that there is a local neural reflex that involves capsaicin-sensitive neurones,
      nitrergic myenteric neurones and vagal motor neurones.

PMID- 12813150
TI  - Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit.
AB  - P2X receptors are ATP-gated cation channels composed of one or more of seven
      different subunits. P2X receptors participate in intestinal neurotransmission but
      the subunit composition of enteric P2X receptors is unknown. In this study, we
      used tissues from P2X3 wild-type (P2X3+/+) mice and mice in which the P2X3
      subunit gene had been deleted (P2X3-/-) to investigate the role of this subunit
      in neurotransmission in the intestine. RT-PCR analysis of mRNA from intestinal
      tissues verified P2X3 gene deletion. Intracellular electrophysiological methods
      were used to record synaptic and drug-induced responses from myenteric neurons in
      vitro. Drug-induced longitudinal muscle contractions were studied in vitro.
      Intraluminal pressure-induced reflex contractions (peristalsis) of ileal segments
      were studied in vitro using a modified Trendelenburg preparation.
      Gastrointestinal transit was measured as the progression in 30 min of a liquid
      radioactive marker administered by gavage to fasted mice. Fast excitatory
      postsynaptic potentials recorded from S neurons (motoneurons and interneurons)
      were similar in tissues from P2X3+/+ and P2X3-/- mice. S neurons from P2X3+/+ and
      P2X3-/- mice were depolarized by application of ATP but not alpha,beta-methylene
      ATP, an agonist of P2X3 subunit-containing receptors. ATP and alpha,beta
      methylene ATP induced depolarization of AH (sensory) neurons from P2X3+/+ mice.
      ATP, but not alpha,beta-methylene ATP, caused depolarization of AH neurons from
      P2X3-/- mice. Peristalsis was inhibited in ileal segments from P2X3-/- mice but
      longitudinal muscle contractions caused by nicotine and bethanechol were similar
      in segments from P2X3+/+ and P2X3-/- mice. Gastrointestinal transit was similar
      in P2X3+/+ and P2X3-/- mice. It is concluded that P2X3 subunit-containing
      receptors participate in neural pathways underlying peristalsis in the mouse
      intestine in vitro. P2X3 subunits are localized to AH (sensory) but not S
      neurons. P2X3 receptors may contribute to detection of distention or intraluminal
      pressure increases and initiation of reflex contractions.

PMID- 12813152
TI  - Loss of force induced by high extracellular [K+] in rat muscle: effect of
      temperature, lactic acid and beta2-agonist.
AB  - Loss of K+ from active muscles, leading to increased [K+]o, has been proposed to
      cause muscle fatigue by reducing excitability. Since exercise increases muscle
      temperature, we investigated the influence of temperature on muscle [K+]o
      sensitivity. Intact rat soleus or extensor digitorum longus (EDL) muscles were
      mounted on force transducers and stimulated electrically to evoke short isometric
      tetani at regular intervals. In each experiment, control force at 4 mM K+ was
      initially determined at every temperature used. In soleus muscles at 20 degrees
      C, 9 mM K+ reduced force to 33 +/- 5 % of control force. Increasing the
      temperature to 30 degrees C restored force to 89 +/- 5 % of control force.
      Likewise, at 30 degrees C 11 mM K+ reduced force to 16 +/- 4 % and increasing the
      temperature to 35 degrees C restored force to 35 +/- 5 %. Similar results were
      obtained using EDL. The force recovery induced by elevating temperature,
      reflecting reduced [K+]o sensitivity, was associated with improved excitability
      assessed from compound action potentials. Force recovery induced by a temperature
      elevation from 20 to 30 degrees C was associated with hyperpolarization (5 mV),
      reduced [Na+]i and a 93 % increase in Na+-K+ pump activity. The force recovery
      was blocked by ouabain. Since intensive exercise leads to lactic acidosis and
      increased plasma catecholamines, the effect of these two factors was also
      investigated. At 11 mM K+, force was completely restored by combining temperature
      elevation (30 to 35 degrees C), L-lactic acid (10 mM) and the beta2-agonist
      salbutamol (10-5 M). We suggest an exercise scenario where the depressing action
      of exercise-induced hyperkalaemia is counteracted by elevated muscle temperature,
      lactic acidosis and catecholamines.

PMID- 12813151
TI  - Sarcoplasmic reticulum calcium release compared in slow-twitch and fast-twitch
      fibres of mouse muscle.
AB  - Experiments were carried out to compare the amplitude and time course of Ca2+
      release from the sarcoplasmic reticulum (SR) in intact slow-twitch and fast
      twitch mouse fibres. Individual fibres within small bundles were injected with
      furaptra, a low-affinity, rapidly responding Ca2+ indicator. In response to a
      single action potential at 16 degrees C, the peak amplitude and half-duration of
      the change in myoplasmic free [Ca2+] (Delta[Ca2+]) differed significantly between
      fibre types (slow-twitch: peak amplitude, 9.4 +/- 1.0 microM (mean +/- S.E.M.);
      half-duration, 7.7 +/- 0.6 ms; fast-twitch: peak amplitude 18.5 +/- 0.5 microM;
      half-duration, 4.9 +/- 0.3 ms). SR Ca2+ release was estimated from Delta[Ca2+]
      with a computational model that calculated Ca2+ binding to the major myoplasmic
      Ca2+ buffers (troponin, ATP and parvalbumin); buffer concentrations and reaction
      rate constants were adjusted to reflect fibre-type differences. In response to an
      action potential, the total concentration of released Ca2+ (Delta[CaT]) and the
      peak rate of Ca2+ release ((d/dt)Delta[CaT]) differed about 3-fold between the
      fibre types (slow-twitch: Delta[CaT], 127 +/- 7 microM; (d/dt)Delta[CaT], 70 +/-
      6 microM ms-1; fast-twitch: Delta[CaT], 346 +/- 6 microM; (d/dt)Delta[CaT], 212
      +/- 4 microM ms-1). In contrast, the half-duration of (d/dt)Delta[CaT] was very
      similar in the two fibre types (slow-twitch, 1.8 +/- 0.1 ms; fast-twitch, 1.6 +/-
      0.0 ms). When fibres were stimulated with a 5-shock train at 67 Hz, the peaks of
      (d/dt)Delta[CaT] in response to the second and subsequent shocks were much
      smaller than that due to the first shock; the later peaks, expressed as a
      fraction of the amplitude of the first peak, were similar in the two fibre types
      (slow-twitch, 0.2-0.3; fast-twitch, 0.1-0.3). The results support the conclusion
      that individual SR Ca2+ release units function similarly in slow-twitch and fast
      twitch mammalian fibres.

PMID- 12813153
TI  - Baclofen inhibits guinea pig magnocellular neurones via activation of an inwardly
      rectifying K+ conductance.
AB  - The GABAB receptors GABAB-R1 and GABAB-R2 have been cloned in several mammalian
      species, and the functional receptor has been shown to exist as a heterodimeric
      complex. We have cloned guinea pig GABAB-R1 and GABAB-R2 receptor sequences and,
      using in situ hybridization and immunocytochemistry for vasopressin (AVP), we
      found that GABAB-R1 and -R2 receptors are expressed in vasopressin neurones of
      the supraoptic (SON) and paraventricular nuclei (PVN). Therefore, we used both
      sharp electrode and whole-cell patch recording techniques to examine the effects
      of the selective GABAB agonist baclofen on SON and PVN magnocellular neurones and
      to determine the coupling of the GABAB receptor to effector pathways. Recordings
      were made in coronal hypothalamic slices from both female (ovariectomized) and
      male guinea pigs. In the presence of tetrodotoxin (TTX), baclofen hyperpolarized
      (DeltaVmax = 5.6 mV, EC50 = 2.3 microM) SON magnocellular neurones (n = 27) under
      current clamp, or induced an outward current that reversed at EK (DeltaImax =
      24.2 pA) in PVN magnocellular neurones (n = 33) under voltage clamp. Seventeen of
      the 24 biocytin-labelled SON magnocellular neurones were identified as AVP
      neurones, and ten of the 33 biocytin-labelled PVN neurones were identified as AVP
      or neurophysin-containing neurones, although all of the cells were clustered in
      the vasopressin-rich core. In the absence of TTX, baclofen activated an outward
      K+ current that hyperpolarized SON and PVN neurones and significantly reduced
      their firing rate. The outward current showed inward rectification and was
      blocked by the K+ channel blocker barium and the GABAB receptor antagonist CGP
      35348. Therefore, GABAB receptors are coupled to inwardly rectifying K+ channels
      in SON and PVN magnocellular neurones and may play a prominent role in modulating
      phasic bursting activity in guinea pig vasopressin neurones.

PMID- 12813155
TI  - Transgenic models for molecular and physiological studies in the central nervous
      system.

PMID- 12813154
TI  - "Delayed" endocytosis is regulated by extracellular Ca2+ in snake motor boutons.
AB  - When cooled below approximately 7 degrees C, recently endocytosed vesicles in the
      motor terminals of the garter snake fail to shed their clathrin coats. Perhaps as
      a result, the terminals complete only about one-half of the compensatory
      endocytosis expected after a given period of stimulation. Upon return to room
      temperature (RT), endocytosis resumes immediately and is complete within minutes.
      This "delayed" endocytosis following release from cold block provides an
      opportunity to study clathrin-dependent endocytotic mechanisms in temporal
      isolation from those events, such as Ca2+ entry and consequent exocytosis, that
      are normally associated with the activation of nerve terminals. We have taken
      advantage of clathrin decoating blockade to examine the rate, temperature
      dependence and extracellular Ca2+ dependence of endocytosis at the snake nerve
      muscle synapse. Endocytosis was fast at RT (complete in < 1 min) and markedly
      faster still at 35 degrees C. Moreover, the rate of endocytosis varied
      significantly with change in [Ca2+]o; the rate at 7.2 mM (single exponential time
      constant, approximately 3 s) was approximately double that at 0 mM (single
      exponential time constant, approximately 7 s). Thus, membrane retrieval via
      clathrin is rapid and, due to its dependence on [Ca2+]o, potentially regulated by
      changes in the milieu of the synaptic cleft during neural activity.

PMID- 12813156
TI  - AMPK activation increases uncoupling protein-3 expression and mitochondrial
      enzyme activities in rat muscle without fibre type transitions.
AB  - The present study examined the effect of chronic activation of 5'-AMP-activated
      protein kinase (AMPK) on the metabolic profile, including uncoupling protein-3
      (UCP-3) and myosin heavy chain (MHC)-based fibre phenotype of rodent fast-twitch
      tibialis anterior muscle. Sprague-Dawley rats were given daily injections of 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), a known activator
      of AMPK, or vehicle (control) for 28 days. After AICAR treatment, UCP-3
      expression at the mRNA level was elevated 1.6 +/- 0.1-fold (P < 0.006) and
      corresponded to a 3.3 +/- 0.2-fold increase in UCP-3 protein content (P <
      0.0001). In addition, the activities of the mitochondrial reference enzymes
      citrate synthase (EC 4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35),
      which are known to increase in proportion to mitochondrial volume density, were
      elevated 1.6-fold (P < 0.006), while the activity of lactate dehydrogenase (EC
      1.1.1.27) was reduced to 80 % of control (P < 0.02). No differences were detected
      after AICAR treatment in the activities of the glycolytic reference enzymes
      glyceraldehydephosphate dehydrogenase (EC 1.2.1.12) or phosphofructokinase (EC
      2.7.1.11), nor were MHC-based fibre-type transitions observed, using
      immunohistochemical or electrophoretic analytical methods. These changes could
      not be attributed to variations in inter-organ signalling by metabolic substrates
      or insulin. We conclude that an AMPK-dependent pathway of signal transduction
      does mimic some of the metabolic changes associated with chronic exercise
      training, but does not affect expression of the MHC-based structural phenotype.
      Thus, the metabolic and MHC-based fibre types do not appear to be regulated in a
      co-ordinated way, but may be independently modified by different signalling
      pathways.

PMID- 12813157
TI  - Transgenesis and neuroendocrine physiology: a transgenic rat model expressing
      growth hormone in vasopressin neurones.
AB  - Human growth hormone (hGH) and bovine neurophysin (bNP) DNA reporter fragments
      were inserted into the rat vasopressin (VP) and oxytocin (OT) genes in a 44 kb
      cosmid construct used to generate two lines of transgenic rats, termed JP17 and
      JP59. Both lines showed specific hGH expression in magnocellular VP cells in the
      hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). hGH was also
      expressed in parvocellular neurones in suprachiasmatic nuclei (SCN), medial
      amygdala and habenular nuclei in JP17 rats; the rat OT-bNP (rOT-bNP) transgene
      was not expressed in either line. Immunohistochemistry and radioimmunoassay
      showed hGH protein in the hypothalamus from where it was transported in varicose
      fibres via the median eminence to the posterior pituitary gland. Immunogold
      electron microscopy showed hGH co-stored with VP-NP in the same granules. The VP
      hGH transgene did not affect water balance, VP storage or release in vivo.
      Drinking 2 % saline for 72 h increased hypothalamic transgene hGH mRNA
      expression, and depleted posterior pituitary hGH and VP stores in parallel. In
      anaesthetised, water-loaded JP17 rats, hGH was released with VP in response to an
      acute hypovolumic stimulus (sodium nitrosopentacyano, 400 microg I.V.). JP17 rats
      had a reduced growth rate, lower anterior pituitary rGH contents, and a reduced
      amplitude of endogenous pulsatile rGH secretion assessed by automated blood
      microsampling in conscious rats, consistent with a short-loop feedback of the VP
      hGH on the endogenous GH axis. This transgenic rat model enables us to study
      physiological regulation of hypothalamic transgene protein production, transport
      and secretion, as well as its effects on other neuroendocrine systems in vivo.

PMID- 12813158
TI  - Reflex responses in the lower leg following landing impact on an inverting and
      non-inverting platform.
AB  - In the lower leg, landing after a jump induces reflexes, the role of which is not
      well understood. This is even more so for reflexes following landing on inverting
      surfaces. The latter condition is of special interest since ankle inversion
      traumata are one of the most common injuries during sport. Most studies have
      investigated ankle inversions during a static standing condition. However, ankle
      injuries occur during more dynamic activities such as jumping. Therefore, the
      present study aimed at reproducing these situations but in a completely safe
      setting. EMG responses were recorded after landing on an inverting surface, which
      caused a mild ankle inversion of 25 deg of rotation (in a range sufficient to
      elicit reflexes but safe enough to exclude sprains). The results are compared
      with data from landing on a non-inverting surface to understand the effect of the
      inversion. In general, landing on the platform resulted in short and long latency
      responses (SLR and LLR) in triceps surae (soleus, gastrocnemius medialis and
      lateralis) and peroneal muscles (long and short peroneal) but not in the tibialis
      anterior muscle. Landing on the inverting platform caused significant LLRs in the
      peroneal muscles (which underwent the largest stretch) but not in the triceps
      muscles. Conversely, landing on a non-inverting platform induced larger SLRs in
      triceps than in the peroneal muscles. Although the peroneal LLRs thus appeared to
      be selectively recruited in an inverting perturbation, their role during such
      perturbations should be limited since the latency of these responses was about 90
      ms while the inversion lasts only 42 ms. The SLRs, if present, had an onset
      latency of around 44 ms. In the period following the inversion, however, the
      responses may be important in preventing further stretch of these muscles.

PMID- 12813159
TI  - Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of
      parvalbumin and calbindin D28k.
AB  - The mechanisms governing the kinetics of climbing fibre-mediated Ca2+ transients
      in spiny dendrites of cerebellar Purkinje cells (PCs) were quantified with high
      resolution confocal Ca2+ imaging. Ca2+ dynamics in parvalbumin (PV-/-) and
      parvalbumin/calbindin D28k null-mutant (PV/CB-/-) mice were compared with
      responses in wild-type (WT) animals. In the WT, Ca2+ transients in dendritic
      shafts were characterised by double exponential decay kinetics that were not due
      to buffered Ca2+ diffusion or saturation of the indicator dye. Ca2+ transients in
      PV-/- PCs reached the same peak amplitude as in the WT but the biphasic nature of
      the decay was less pronounced, an effect that could be attributed to PV's slow
      binding kinetics. In contrast, peak amplitudes in PV/CB-/- PCs were about two
      times higher than in the WT and the decay became nearly monophasic. Numerical
      simulations indicate that the residual deviation from a single exponential decay
      in PV/CB-/- is due to saturation of the Ca2+ indicator dye. Furthermore, the
      simulations imply that the effect of uncharacterised endogenous Ca2+ binding
      proteins is negligible, that buffered diffusion and dye saturation significantly
      affects spineous Ca2+ transients but not those in the dendritic shafts, and that
      neither CB nor PV undergoes saturation in spines or dendrites during climbing
      fibre-evoked Ca2+ transients. Calbindin's medium-affinity binding sites are fast
      enough to reduce the peak amplitude of the Ca2+ signal. However, similar to PV,
      delayed binding by CB leads to biphasic Ca2+ decay kinetics. Our results suggest
      that the distinct kinetics of PV and CB underlie the biphasic kinetics of
      synaptically evoked Ca2+ transients in dendritic shafts of PCs.

PMID- 12813160
TI  - Simulated screening for prostate cancer: the useful model.

PMID- 12813161
TI  - A new member of the growing family of metastasis suppressors identified in
      prostate cancer.

PMID- 12813162
TI  - Who knows whether acrylamide in food is hazardous to humans?

PMID- 12813163
TI  - Of cancer and cholesterol: studies elucidate anticancer mechanisms of statins.

PMID- 12813164
TI  - First proteasome inhibitor approved for multiple myeloma.

PMID- 12813165
TI  - Predicting the future: projections help researchers allocate resources.

PMID- 12813166
TI  - Stat bite: global cancer incidence, 2000.

PMID- 12813167
TI  - Lowering immune suppression drugs post-transplant may cut cancer risk.

PMID- 12813169
TI  - Developing inhibitors of the epidermal growth factor receptor for cancer
      treatment.
AB  - Progress in identifying and understanding the molecular and cellular causes of
      cancer has led to the discovery of anomalies that characterize cancer cells and
      that represent targets for the development of cancer therapeutics. One such
      target is the epidermal growth factor receptor (EGFR), a transmembrane protein
      that is frequently dysregulated in cancer cells. Preclinical studies have
      demonstrated that pharmacologic interventions that abrogate EGFR dysfunction
      result in antitumor effects. On the basis of these findings, therapeutic
      strategies to inhibit EGFR and EGFR-related pathways, including the use of
      monoclonal antibodies against the extracellular ligand-binding domain of EGFR and
      small-molecule inhibitors of the tyrosine kinase activity of EGFR, have entered
      clinical testing where they have demonstrated favorable safety profiles and
      adequate clinical pharmacology. Further development of these agents has been
      fueled by evidence of their antitumor activities, both as single agents and in
      combination with chemotherapy and radiation therapy. Areas that require
      investigation are the definition of patient populations most likely to derive
      benefits from these drugs, the implementation of biologic correlative studies to
      aid the selection of pharmacodynamically relevant doses and schedules, the
      characterization of population pharmacokinetic parameters and pharmacogenomic
      variables, and the most appropriate clinical scenario for proceeding with the
      clinical development of these agents.

PMID- 12813170
TI  - Lead times and overdetection due to prostate-specific antigen screening:
      estimates from the European Randomized Study of Screening for Prostate Cancer.
AB  - BACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead
      time) and detects cancers that would not have been diagnosed in the absence of
      screening (overdetection). Both consequences have considerable impact on the net
      benefits of screening. METHODS: We developed simulation models based on results
      of the Rotterdam section of the European Randomized Study of Screening for
      Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of
      prostate cancer were identified, and on baseline prostate cancer incidence and
      stage distribution data. The models were used to predict mean lead times,
      overdetection rates, and ranges (corresponding to approximate 95% confidence
      intervals) associated with different screening programs. RESULTS: Mean lead times
      and rates of overdetection depended on a man's age at screening. For a single
      screening test at age 55, the estimated mean lead time was 12.3 years (range =
      11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75,
      the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%),
      respectively. For a screening program with a 4-year screening interval from age
      55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years),
      and the overdetection rate was 48% (range = 44%-55%). This screening program
      raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a
      relative increase of 65% (range = 56%-87%). In annual screening from age 55 to
      67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime
      prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or
      quadrennial screening to the age of 75 would result in at least two cases of
      overdetection for every clinically relevant cancer detected. CONCLUSIONS: These
      model-based lead-time estimates support a prostate cancer screening interval of
      more than 1 year.

PMID- 12813171
TI  - Effects of raf kinase inhibitor protein expression on suppression of prostate
      cancer metastasis.
AB  - BACKGROUND: Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated
      activation of mitogen-activated protein/extracellular signal-regulated kinase
      kinase (MEK), is expressed at lower levels in human C4-2B metastatic prostate
      cancer cells than in the parental non-metastatic LNCaP prostate cancer cells from
      which they were derived. We examined whether RKIP functions as a suppressor of
      metastasis. METHODS: Immunohistochemistry was used to detect RKIP expression in
      clinical samples of primary prostate cancer and prostate cancer metastases. LNCaP
      and C4-2B cells were stably transfected with plasmids that constitutively
      expressed antisense and sense RKIP cDNA, respectively, or with empty vector.
      Assays of cell proliferation, soft-agar colony formation, and in vitro cell
      invasion were used to examine the malignant phenotypes of the transfected cells.
      An orthotopic murine model was used to examine the effect of expressing RKIP in
      C4-2B cells on the development of spontaneous metastasis. RESULTS: Clinical
      samples of primary prostate cancer had detectable RKIP expression, whereas
      clinical samples of prostate cancer metastases did not. There were no differences
      in the in vitro proliferation rate or colony-forming ability between the control
      vector-transfected and sense RKIP vector-transfected C4-2B cells or between the
      control vector-transfected and the antisense RKIP vector-transfected LNCaP cells.
      Overexpression of RKIP in C4-2B cells was associated with decreased in vitro cell
      invasion, decreased development of lung metastases in vivo, and decreased
      vascular invasion in the primary tumor but did not affect primary tumor growth in
      mice. CONCLUSIONS: RKIP does not influence the tumorigenic properties of human
      prostate cancer cells. It appears to be a novel and clinically relevant
      suppressor of metastasis that may function by decreasing vascular invasion.

PMID- 12813172
TI  - Weak yet distinct mutagenicity of acrylamide in mammalian cells.
AB  - BACKGROUND: Despite concern raised with the announcement that common heating
      processes such as frying introduce acrylamide, a known rodent carcinogen, into
      food, the mutagenicity of acrylamide in mammalian DNA is controversial. METHODS:
      Big Blue mouse embryonic fibroblasts, which carry a lambda phage cII transgene,
      were treated with acrylamide. Formation of DNA adducts was determined by terminal
      transferase-dependent polymerase chain reaction. Mutational events were detected
      with a lambda phage-based mutagenesis assay and expressed as the frequency of the
      number of mutant cII plaques per total number of plaques screened. Mutations were
      confirmed by DNA sequence analysis. All statistical tests were two-sided.
      RESULTS: In vitro treatment of the cells with acrylamide at millimolar
      concentrations induced DNA adducts along the cII gene. Treatment with acrylamide
      at micromolar concentrations increased the frequency of mutations in the cII gene
      up to twofold relative to control treatment (13.8 x 10(-5), 95% confidence
      interval [CI] = 12.3 to 15.3 x 10(-5) versus 6.9 x 10(-5), 95% CI = 6.5 to 7.3 x
      10(-5), df = 2, 21; P<.001; ANOVA). The specificity of acrylamide in inducing cII
      gene mutations was shown by a statistically significantly different mutational
      spectrum from that in control-treated cells, with an excess of G --> C
      transversions and A --> G transitions (P =.024; Adams and Skopek test). Although
      some of the frequently mutated sites in the cII gene co-localized with sites of
      preferential DNA adduct formation, there was no direct relationship. CONCLUSION:
      Acrylamide had distinct mutagenicity in transgenic mouse embryonic fibroblast
      cells, which might potentially be ascribed to its DNA adduct-inducing property.
      Whether acrylamide has the same effects on human cells is yet to be determined.

PMID- 12813173
TI  - Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against
      leukemia, myeloma, and colon cancer cells.
AB  - BACKGROUND: 1,25-Dihydroxyvitamin D(3) inhibits growth of several types of human
      cancer cells in vitro, but its therapeutic use is hampered because it causes
      hypercalcemia. 19-nor-1,25-Dihydroxyvitamin D(2) (paricalcitol) is a noncalcemic
      vitamin D analog that is approved by the Food and Drug Administration for the
      treatment of secondary hyperparathyroidism. We investigated the antitumor
      activity and mechanism of action of paricalcitol in vitro and in vivo. METHODS:
      Effects of paricalcitol on proliferation, the cell cycle, differentiation, and
      apoptosis were examined in cancer cell lines. Effects on tumor growth were
      examined with colon cancer cell xenografts in nude mice (five in the experimental
      group and five in the control group). The interaction of paricalcitol with the
      vitamin D receptor (VDR) in mononuclear spleen cells and myeloid stem cells from
      wild-type and VDR knockout mice was examined. All statistical tests were two
      sided. RESULTS: Paricalcitol inhibited the proliferation of myeloid leukemia cell
      lines HL-60, NB-4, and THP-1 cells at an effective dose that inhibited growth 50%
      (ED(50)) of 2.4-5.8 x 10(-9) M by inducing cell cycle arrest and differentiation.
      Paricalcitol inhibited the proliferation of NCI-H929 myeloma cells at an ED(50)
      of 2.0 x 10(-10) M by inducing cell cycle arrest and apoptosis. Paricalcitol also
      inhibited the proliferation of colon cancer cell lines HT-29 (ED(50) = 1.7 x 10(
      8) M) and SW837 (ED(50) = 3.2 x 10(-8) M). HT-29 colon cancer xenografts in
      paricalcitol-treated nude mice were smaller (1044 mm(3) and 1752 mm(3),
      difference = 708 mm(3), 95% confidence interval = 311 to 1104 mm(3); P =.03) and
      weighed less (1487 mg and 4162 mg, difference = 2675 mg, 95% confidence interval
      = 2103 to 3248 mg; P<.001) than those in vehicle-treated mice. Paricalcitol
      induced committed myeloid hematopoietic stem cells from wild-type but not from
      VDR knockout mice to differentiate as macrophages. CONCLUSION: Paricalcitol has
      anticancer activity against myeloid leukemia, myeloma, and colon cancer cells
      that may be mediated through the VDR. Because it has been approved by the Food
      and Drug Administration, clinical trials of this agent in certain cancers are
      reasonable.

PMID- 12813174
TI  - Soy, isoflavones, and breast cancer risk in Japan.
AB  - BACKGROUND: Although isoflavones, such as those found in soy, have been shown to
      inhibit breast cancer in laboratory studies, associations between consumption of
      isoflavone-containing foods and breast cancer risk have been inconsistent in
      epidemiologic studies. We evaluated the relationship between isoflavone
      consumption and breast cancer risk among women in the Japan Public Health Center
      Based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study).
      METHODS: In January 1990, 21 852 Japanese female residents (aged 40-59 years)
      from four public health center areas completed a self-administered questionnaire,
      which included items about the frequency of soy consumption. Through December
      1999 and 209 354 person-years of follow-up, 179 women were diagnosed with breast
      cancer. Cox proportional hazards regression was used to estimate the relative
      risks (RRs) and 95% confidence intervals (CIs) for breast cancer in relation to
      consumption of miso soup, soyfoods, and estimated isoflavones. All statistical
      tests were two-sided. RESULTS: Consumption of miso soup and isoflavones, but not
      of soyfoods, was inversely associated with the risk of breast cancer. The
      associations did not change substantially after adjustment for potential
      confounders, including reproductive history, family history, smoking, and other
      dietary factors. Compared with those in the lowest quartile of isoflavone intake,
      the adjusted RRs for breast cancer for women in the second, third, and highest
      quartiles were 0.76 (95% CI = 0.47 to 1.2), 0.90 (95% CI = 0.56 to 1.5), and 0.46
      (95% CI = 0.25 to 0.84), respectively (P(trend) =.043). The inverse association
      was stronger in postmenopausal women (P(trend) =.006). CONCLUSION: In a
      population-based, prospective cohort study in Japan, frequent miso soup and
      isoflavone consumption was associated with a reduced risk of breast cancer.

PMID- 12813175
TI  - Glycemic load, carbohydrate intake, and risk of colorectal cancer in women: a
      prospective cohort study.
AB  - Mounting evidence suggests that high circulating levels of insulin might be
      associated with increased colorectal cancer risk. The glycemic effects of diets
      high in refined starch may increase colorectal cancer risk by affecting insulin
      and/or insulin-like growth factor-I levels. We examined the association between
      dietary intake and colorectal cancer risk in a cohort of 49 124 women
      participating in a randomized, controlled trial of screening for breast cancer in
      Canada. Linkages to Canadian mortality and cancer databases yielded data on
      mortality and cancer incidence up to December 31, 2000. During an average 16.5
      years of follow-up, we observed 616 incident cases of colorectal cancer (436
      colon cancers, 180 rectal cancers). Rate ratios for colorectal cancer for the
      highest versus the lowest quintile level were 1.05 (95% confidence interval [CI]
      = 0.73 to 1.53; P(trend) =.94) for glycemic load, 1.01 (95% CI = 0.68 to 1.51;
      P(trend) =.66) for total carbohydrates, and 1.03 (95% CI = 0.73 to 1.44; P(trend)
      =.71) for total sugar. Our data do not support the hypothesis that diets high in
      glycemic load, carbohydrates, or sugar increase colorectal cancer risk.

PMID- 12813176
TI  - Re: Italian randomized trial among women with hysterectomy: tamoxifen and hormone
      dependent breast cancer in high-risk women.

PMID- 12813177
TI  - Re: Italian randomized trial among women with hysterectomy: tamoxifen and hormone
      dependent breast cancer in high-risk women.

PMID- 12813179
TI  - Re: Is TIG1 a new tumor suppressor in prostate cancer?

PMID- 12813180
TI  - Letter.

PMID- 12813181
TI  - We're all right Jack?
AB  - "Planning for Canada's Health Workforce: Looking Back, Looking Forward" is a
      readable overview that presents a pastiche of data collected by a number of
      organizations. The paper deals with a policy area of immense importance to the
      future sustainability of Canada's health system and therefore warrants attention.
      In the remarks that follow, we would like to amplify the following points: There
      is a major disconnect between the tenor of the invited essay and the profound
      sense of urgency in addressing the emerging shortages of health human resources
      (HHR) that are evident both nationally and internationally. There has been, in
      fact, very little progress in the comprehensive measurement of the health
      workforce since the 1964 Hall report. Perhaps most important, there is an
      absolute need to involve the practising community more in the collection and
      analysis of health information.

PMID- 12813182
TI  - A U.S. perspective on AHSCs: a future of increased diversification.
AB  - Academic Health Sciences Centres (AHSCs) have long been viewed much as the
      historic battleship - possessing great force, power and bulk, but increasingly
      vulnerable to forays of lighter and more agile competitors. This commentary
      reviews the efforts of leaders of AHSCs in the United States to reposition their
      institutions at the centre of integrated delivery systems, partly as a result of
      greatly increased reliance on clinical revenue to support the historic teaching
      mission. While Lozon and Fox point to increased involvement of AHSCs in broad
      regional systems of care financed through a coordinated strategy, integrated
      systems in the United States may be fragmenting as marketplace-driven financial
      schemes actually discourage integrated care. From the perspective of
      organizational theory, the future seems to imply a diversification of
      organizational forms for the AHSCs in the United States, with a corresponding
      strategy of lessening reliance on clinical revenues through enhancement of
      research funding.

PMID- 12813183
TI  - Memorandum to the Premier from the Deputy Minister of Health.

PMID- 12813184
TI  - Guest Editorial: Does Good Nutrition Conflict With Cultural Sensitivities?
AB  - In this era of political correctness, we avoid giving the best dietary advice for
      optimal health and disease prevention for all population groups.

PMID- 12813185
TI  - Can Chinese Children Drink Milk?
AB  - A controlled milk-intervention trial in Chinese schoolchildren showed that
      participants were able to consume 330 mL of milk every school day for 2 years.

PMID- 12813187
TI  - Fast-Casual Dining: Our Next Eating Passion?
AB  - Americans have a new speedy-eating passion: fast-casual dining! Does this mean
      that now we can forget about McDonald's, Burger King, KFC, and the other fast
      food restaurants that nutritionists have been railing against? Are they
      yesterday's news?

PMID- 12813186
TI  - Dairy Foods: Are They Politically Correct?
AB  - This article considers the scientific evidence on the prevalence and management
      of verified lactose intolerance and the growing misperception that dairy foods
      should be avoided because ethnic populations cannot tolerate them. Healthcare
      professionals, in particular, must understand why eliminating dairy foods is
      rarely necessary and is generally undesirable. The genetically programmed ability
      to digest the milk sugar lactose normally declines throughout childhood in all
      ethnic groups. Only rarely does lactase nonpersistence result in verifiable
      lactose intolerance. The intolerance-gastrointestinal symptoms, such as diarrhea,
      bloating, and abdominal cramping-is easily managed when it occurs and is not a
      barrier to the consumption of 2 to 3 servings of calcium-rich dairy foods, as
      encouraged by the Dietary Guidelines for Americans.

PMID- 12813188
TI  - Do Nuts Have a Place in a Healthful Diet?
AB  - A wealth of nutrition information has been published during the past decade on
      the healthful nature of nuts. As nut consumption increases, cardiovascular
      disease risk decreases. This cardioprotective effect of nut consumption is beyond
      what would be predicted from the fatty acid profile alone. Nuts are a rich source
      of many other nutrients and bioactive compounds, similar to other whole-plant
      foods, such as fruits and vegetables. Additional studies during the next decade
      will delineate additional healthful nutrients of these foods.

PMID- 12813189
TI  - Provisional Recommended Soy Protein and Isoflavone Intakes for Healthy Adults:
      Rationale.
AB  - Health professionals and consumers are seeking guidance regarding appropriate soy
      intake levels. Several different types of evidence that support of our
      recommendation that adults should consume 15 g (range 10-25 g) soy protein and 50
      mg isoflavones (range 30-100 mg)/day are presented.

PMID- 12813190
TI  - Treatment of iodine negative, thyroglobulin positive, thyroid cancer patients: do
      we miss the target when we shoot in the dark?

PMID- 12813191
TI  - Estimation of thyroid mass in Graves' disease by a scintigraphic method.
AB  - scintigraphic method for the estimation of the thyroid mass in patients with
      Graves' disease is described. The method was first standardized using thyroid
      phantoms with eight different volumes ranging from 5 to 110 cm(3). The planar and
      single photon emission computed tomography (SPECT) images of each phantom were
      acquired with four different activities [3.7 MBq (100 microCi), 11.1 MBq (300
      microCi), 22.2 MBq (600 microCi) and 37 MBq (1.0 mCi) of 99mTc-pertechnetate]
      with a 20% window symmetrically placed over the photopeak of 99mTc. The thyroid
      lobes were enclosed with the help of regions of interest (ROI) tools and a
      threshold was selected to identify the thyroid boundaries. The same threshold was
      used in all slices of an image. In the phantom study, a 20% threshold for planar
      images and a 30% threshold for SPECT were found to be optimum for measuring the
      thyroid volume. The volume from planar images was calculated by the formula
      described by Allen and Goodwin (The scintillation counter as an instrument for in
      vivo determination of thyroid weight. Radiology 1952; 58: 68-79), whereas, in
      SPECT images, the sum of the slice areas was multiplied by the slice thickness.
      The estimated volume of each phantom was compared and correlated with its actual
      volume. After standardization of the technique with phantom studies, planar
      scintigraphy (with 20% threshold) in 51 patients and SPECT (with 30% and 35%
      threshold) in 40 patients with Graves' disease were performed to estimate the
      thyroid size. The thyroid size was also estimated by ultrasonography, which
      showed good agreement with the scintigraphic method, particularly with SPECT.

PMID- 12813192
TI  - Quantification of absorbed doses to urine bladder depending on drinking water
      during radioiodine therapy to thyroid cancer patients: a clinical study using
      MIRDOSE3.
AB  - The object of the study was to quantify the absorbed doses to urinary bladder
      using MIRDOSE3 (medical internal radiation dose package program) depending on
      drinking water after giving radioiodine dose to thyroid cancer patients. Twenty
      nine female thyroid cancer patients (aged 40-60 years, mean 50 years) were
      selected. The therapeutic doses ranged from 3700 to 7400 MBq of 131I. The
      radioiodine uptake was measured at 1 cm distance from three organs (previously
      marked), the thyroid, thigh and stomach, by using a calibrated Eberline ESP-2 GM
      counter, with a special arrangement of each patient. Urine samples were collected
      every 12 h for first 72 h, and then every 24 h for the next 96 h. The individual
      biological half-life of excreted urine was calculated using individual effective
      half-life. Absorbed doses were calculated for an adult female phantom using the
      dynamic bladder model of MIRDOSE3 program in two phases: firstly, for different
      voiding intervals; and secondly, depending on individual drinking water. An
      average of 85% of the total dose passed through the urinary tract within the
      first 72 h, with a biological half-life of 28.5+/-0.747 h, and 9% for the next 96
      h with a biological half life of 118.43+/-0.645 h. The voiding interval shows
      great impact on total absorbed dose to bladder and water supplementation needs to
      be intensified to reduce absorbed doses to bladder wall for the first 3 days.

PMID- 12813193
TI  - Parathyroid scintigraphy with 99mTc-MIBI and 123I subtraction: a comparison with
      magnetic resonance imaging and ultrasonography.
AB  - The aim of this study was to evaluate the efficacy of 99mTc-MIBI and 123I
      subtraction scintigraphy for the detection of abnormal parathyroid glands to be
      referred for surgical treatment. Thirty-nine consecutive patients, including 35
      primary and four secondary cases of hyperparathyroidism, were evaluated. 99mTc
      MIBI/123I subtraction scintigraphy (MIBI/I) was performed on all patients, and
      the results were compared with delayed images of 99mTc-MIBI (D-MIBI), magnetic
      resonance imaging (MRI) and ultrasonography (US). The overall sensitivity of
      MIBI/I, MRI, US and D-MIBI was 55.9%, 43.4%, 50.8% and 39.0%, respectively. In
      cases of single-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was
      62.1%, 48.3%, 55.2% and 44.8%, respectively. In cases of multi-gland disease, the
      sensitivity of MIBI/I, MRI, US and D-MIBI was 50.0%, 37.5%, 46.7% and 36.7%,
      respectively. In cases of parathyroid adenoma, the sensitivity of MIBI/I, MRI, US
      and D-MIBI was 71.4%, 50.0%, 71.4% and 50.0%, respectively. In cases of
      parathyroid hyperplasia, the sensitivity of MIBI/I, MRI, US and D-MIBI was 55.2%,
      42.3%, 50.0% and 39.7%, respectively. It is concluded that 99mTc-MIBI/123I
      subtraction is more useful than the delayed imaging of 99mTc-MIBI, MRI and US.

PMID- 12813194
TI  - Comparison of 99mTc tetrofosmin gated SPECT measurements of left ventricular
      volumes and ejection fraction with MRI over a wide range of values.
AB  - The calculation of ejection fraction using gated single photon emission computed
      tomography (SPECT) has been widely validated against a range of other techniques.
      There have been fewer studies validating left ventricular volumes. We compared
      quantitative gated SPECT (QGS) with magnetic resonance imaging (MRI) measurements
      of left ventricular ejection fraction and end diastolic volume in 50 patients
      with a large range of ventricular dimensions. MRI data were obtained using a
      turbo gradient echo pulse sequence (TGE) in 17 patients and a steady state free
      precession pulse sequence (SSFP) in 33 patients. There was good correlation
      between ejection fraction and end diastolic volume measurements from SPECT and
      MRI (r=0.82, r=0.90, respectively) but the mean SPECT values were significantly
      lower (ejection fraction, 6.6+/-6.4% points; end diastolic volume, 18.4+/-25.4
      ml) than those obtained from MRI. Bland-Altman analysis showed some large
      differences in individual patients but no trends in the data either in ejection
      fraction over a range from 15% to 70% or in end diastolic volume, range 75-400
      ml. SSFP gave a larger difference for end diastolic volume measurement compared
      to SPECT than did TGE, although this difference did not reach significance. Both
      SSFP and TGE gave similar values for the difference between MRI and SPECT for the
      measurement of ejection fraction. We suggest that the difference in EF may be a
      result of 8 frames being used for gating in QGS but 12-18 for MR. Differences in
      volumes may be related to the different spatial resolution and the exclusion or
      inclusion of trabeculation and papillary muscles between SPECT and MRI.
      Differences between SSFP and TGE may be caused by differing delineation of the
      endocardial border, dependent on the particular acquisition sequence. In
      conclusion, QGS values correlated well with MRI, but a correction factor may be
      needed if direct comparison is made.

PMID- 12813195
TI  - Validation of planar and tomographic radionuclide ventriculography by a dynamic
      ventricular phantom.
AB  - Although there is increasing interest in the automatic processing of tomographic
      radionuclide ventriculography (TRV) studies, validation is mainly limited to a
      comparison of TRV results with data from planar radionuclide ventriculography
      (PRV) or gated perfusion single photon emission computed tomography (SPECT). The
      aim of this study was to use a dynamic physical cardiac phantom to validate the
      ejection fraction (EF) and volumes from PRV and TRV studies. A new dynamic left
      ventricular phantom was constructed and used to obtain 21 acquisitions in the
      planar and tomographic mode. The directly measured volumes and EFs of the phantom
      during the acquisitions were considered as the gold standard for comparison with
      TRV and PRV. EFs were calculated from PRV by background-corrected end-diastolic
      and end-systolic frames. Volumes and EFs were calculated from TRV by region
      growing with different lower thresholds to search for the optimal threshold. EF
      from PRV correlated significantly with the real EF (r=0.94, P=0.00). The optimal
      threshold value for volume calculation from TRV in 336 cases was 50% (r=0.98,
      P=0.00) yielding the best slope after linear regression. When considering these
      calculated end-diastolic and end-systolic volumes, EF correlated well (r=0.99,
      P=0.00) with the real EF, and this correlation was significantly (P=0.04) higher
      than that of the EF from PRV. Our experiments prove that EF measured by TRV
      yields more accurate results compared with PRV in dynamic cardiac phantom
      studies.

PMID- 12813196
TI  - 99mTc-MIBI myocardial perfusion imaging in myocarditis.
AB  - Myocardial perfusion imaging with technetium-99m-labelled methoxyisobutyl
      isonitrile single photon emission computed tomography (99mTc-MIBI SPECT) has
      proven to be an important clinical procedure in assessing the severity of
      myocardial ischaemia. The uptake and clearance of 99mTc-MIBI by the myocardium is
      affected by cell viability and membrane integrity. Consequently, infectious
      diseases, such as myocarditis, may also affect myocardial perfusion by inducing
      local inflammation and necrosis. We compared 99mTc-MIBI myocardial perfusion
      imaging with other heart monitoring methods in order to assess its value in the
      diagnosis of children with Coxsackie viral myocarditis. We examined 46 patients
      (age, 3-12 years) with Coxsackie viral myocarditis using 99mTc-MIBI myocardial
      perfusion imaging and compared the perfusion data with myocardial enzymes,
      electrocardiographic findings and echocardiography. Regions of hypoperfusion were
      found in all 46 patients. Seventeen patients (37%) showed two or more areas of
      diminished perfusion. Myocardial hypoperfusion was mild-to-moderate (<30%) in 33
      (72%) patients and severe (>30%) in 13 (28%) patients. Characteristic creatine
      kinase isoenzyme (CK-MB) increases, ST-T segment changes and diminished heart
      function were significantly correlated with reduced myocardial perfusion (all
      comparisons P<0.05). The results of this study suggest that the presence of
      myocardial uptake of 99mTc-MIBI may be a marker of myocardial inflammation and
      necrosis. All 46 patients with Coxsackie viral myocarditis showed a certain
      degree of reduced perfusion. When the perfusion findings were compared with other
      parameters, it was shown that myocardial enzyme levels, ST-T segment changes and
      left ventricular function correlated well with the 99mTc-MIBI-established
      perfusion defect severity. 99mTc-MIBI SPECT imaging is therefore helpful in
      providing additional diagnostic information in patients with Coxsackie viral
      myocarditis.

PMID- 12813197
TI  - Brain metabolism in the cerebellum and visual cortex correlates with
      neuropsychological testing in patients with Alzheimer's disease.
AB  - This study was designed to measure glucose metabolic deficits in areas not
      typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission
      tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to
      correlate such findings with subtle neuropsychological impairment. FDG-PET scans
      on 38 AD patients with no clinical evidence of visual, spatial or motor deficits
      were acquired on the PET HEAD scanner 40 min following the intravenous
      administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed
      blindly using a region of interest (ROI) template with regions for the primary
      visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from
      the ROIs of these regions were normalized to whole brain activity and the results
      were compared with psychometric and neuropsychological measures. A number of
      significant correlations were found between these structures and various
      neuropsychological measures (P<0.05). Specifically, there were significant
      correlations between clock drawing and the cerebellum activity; memory and
      activity in the PVC, SVC and cerebellum; social score and activity in the PVC and
      left cerebellum; judgement and activity in the right SVC and right PVC; and the
      overall Mini-Mental State Examination and activity in the PVC, SVC and
      cerebellum. The results of this study suggest that metabolism in areas not
      typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and
      cerebellum, is correlated with deficits in neuropsychological function. This may
      have important clinical and pathophysiological implications in the study of AD
      and other illnesses of dementia.

PMID- 12813198
TI  - Influence of early furosemide injection on the split renal function.
AB  - The split renal function, obtained using Technetium 99m mercaptoacetyltriglycine
      renography, is currently considered as a robust, accurate and reproducible
      parameter, provided that it is calculated at a time when no escape of the tracer
      from the kidney has occurred. The question arises as to whether the simultaneous
      administration of furosemide with the tracer (F0 test) might accelerate the
      escape of the tracer, resulting in an underestimation of the split renal
      function. From a large database, we selected 36 clinically stable children in
      whom both F0 and F+20 (administration of furosemide 20 min after the tracer)
      diuretic renography had been performed. In all cases, the F+20 test preceded the
      F0 test. The mean interval between the two tests was 17 months. The split renal
      function was calculated on the basis of the 1-2 min background-corrected renal
      activity using the integral method, slope method and Rutland-Patlak plot. In
      order to evaluate the effect on the split renal function of an early escape of
      the tracer, the patients were analysed according to the T(max) value of the
      renogram for both the F0 and F+20 tests. For the F+20 test, all T(max) values
      were more than 3 min. For the F0 test, the T(max) value was more than 3 min in 53
      kidneys and less than 3 min in 19 kidneys (unilateral in all 19 patients). For
      the F0 test, for the kidneys with a T(max) value of less than 3 min, there was a
      tendency to underestimate the split renal function, taking as reference the split
      renal function observed in the F+20 test. This observation, however, was only
      statistically significant for the slope method (P=0.03). There was a tendency for
      lower values with the Rutland-Patlak plot (P=0.07), but, for the integral method,
      no difference was observed (P=0.5). In conclusion, the simultaneous
      administration of furosemide with the tracer induces an early acceleration of
      renal transit. This should be taken into account when calculating the split renal
      function, for example by favouring the integral method.

PMID- 12813199
TI  - Diuretic renogram clearance half-times in the diagnosis of obstructive uropathy:
      effect of age and previous surgery.
AB  - Diuretic renography with radiotracers has been used successfully to diagnose
      obstruction in patients with hydronephrosis. Controversy persists with regard to
      the best approach for the interpretation of renogram curves: visual analysis or a
      quantitative index, i.e. the clearance half-time. The latter is often reported to
      be in the intermediate or non-diagnostic range. It is important to measure the
      incidence of equivocal half-times in various subsets of patients with
      hydronephrosis in order to determine in which settings the measurement of this
      index may be clinically useful. We performed a retrospective study of diuretic
      renograms performed at our institution between 1997 and 2000 for the evaluation
      of suspected uretero-pelvic junction (UPJ) obstruction. Vigorous intravenous
      hydration, exceeding current guidelines, was employed in these patients. Three
      hundred and seventy-seven renogram curves in 205 patients were analysed. Patients
      were divided into three groups: >1 year of age; <or=1 year of age; and those who
      had previously undergone surgical correction of obstruction regardless of age.
      Patients with reflux or anatomical abnormalities of the urinary tract, those with
      chronic renal failure, those with bilateral normal clearances before furosemide
      administration and those with unilateral normal clearances before furosemide
      administration with contralateral poor renal function were excluded. In the
      remaining 119 patients, 205 clearance half-times were classified as normal before
      furosemide, normal after furosemide (half-time, <10 min), prolonged (half-time,
      >20 min) or intermediate (half-time, 10-20 min). In patients >1 year of age, 37%
      of 101 renograms showed normal half-times before furosemide, 20% showed normal
      half-times after furosemide, 44% showed prolonged half-times and none (0%) showed
      an intermediate half-time. In patients </=1 year of age, there was a
      statistically significantly different distribution, with 48% of 64 renograms
      showing normal washout before furosemide, 16% showing normal clearance after
      furosemide, 19% showing abnormal half-times and 17% showing intermediate half
      times. In 33 renograms from patients who had undergone corrective surgery, 49%
      had normal half-times, 24% had prolonged half-times and 27% had intermediate half
      times. It can be concluded that, when using the selection criteria, hydration,
      acquisition and processing protocols and half-time definition employed in this
      study, the addition of a clearance measurement in patients older than 1 year with
      suspected UPJ disease enhances patient classification and may improve the
      diagnostic confidence. There was a significantly higher incidence of intermediate
      half-times in patients with native disease aged <1 year than in those >1 year.
      Caution is advised when interpreting this finding in this age group. The
      measurement of washout was less useful in patients who had undergone a corrective
      procedure, because of the high rate of 'indeterminate' and 'abnormal' values in
      spite of successful surgery. Vigorous intravenous hydration, exceeding current
      standards, may have contributed to the lower incidence of intermediate half-times
      than reported previously.

PMID- 12813200
TI  - 99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative
      assessment of hepatectomy in relation to percutaneous transhepatic portal
      embolization.
AB  - We have devised an original predictive residual index (PRI) using 99mTc
      diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA)
      liver dynamic SPET for the pre-operative assessment of hepatectomy, including the
      prediction of residual liver function before hepatectomy. The aim of this study
      was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET
      before and after percutaneous transhepatic portal embolization (PTPE) to induce
      compensatory hypertrophy of the remnant lobe, and to compare the results with the
      prognosis after hepatectomy. The subjects included eight patients with
      cholangiocellular carcinoma, five with gallbladder cancer, four with
      hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver
      dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic
      SPET with 35 continuous rotations was performed to obtain the k-value according
      to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the
      liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation
      consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition
      time of each rotation was 35 s. We devised an original PRI by combining the k
      value with functional liver volume which were measured by liver dynamic SPET.
      Hepatectomy was performed following the second SPET. The correlation between the
      PRI and post-operative patient prognosis was investigated retrospectively. The
      functional liver volume of the remnant lobe and the PRI significantly increased
      after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001,
      respectively). Regarding the relationship between the PRI and the clinical course
      following surgery, post-operative complications were observed in only two
      patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI
      was above 0.400, no patient had symptoms of hepatic failure. The results of this
      study suggest that, when the PRI value is above 0.400, there is a low probability
      of hepatic failure after hepatectomy. We conclude that the PRI devised in this
      study is useful in the pre-operative assessment of hepatectomy after PTPE.

PMID- 12813201
TI  - Correlation of pulmonary 99mTc-DTPA ventilation and 99mTc-MAA perfusion scans
      with pulmonary function tests in asymptomatic asthmatic children.
AB  - Our objective was to examine and correlate 99mTc-diethylenetriaminopentaacetic
      acid (99mTc-DTPA) ventilation and 99mTc-macroaggregated albumin (99mTc-MAA)
      perfusion (V/Q) lung scans with spirometry in asymptomatic asthmatic children. We
      evaluated 89 subjects (age range, 6-15 years; mean age, 9.4 years), all with at
      least 70% predicted forced expiratory volume in 1 s (FEV(1)). There were four V/Q
      scan patterns: normal in 38 (42.7%), inhomogeneous ventilation in 11 (12.4%),
      matched defects in 25 (28.3%) and mismatched perfusion defects in 13 (14.6%). The
      maximal mid-expiratory flow rate (MMEF) of the normal scan group was
      significantly different from that in the other groups. The MMEF of the
      inhomogeneous group was significantly different from that in the matched defect
      group and the mismatched perfusion defect group. No other significant differences
      in spirometric indices were found. In two children with perfusion defects,
      pulmonary arteriograms demonstrated no obstructive lesions. In conclusion, lung
      scans provide diagnostic information in asymptomatic asthmatic children, even
      when they are uncooperative. Abnormal scans are common in these children and are
      significantly correlated with reduced MMEF (% predicted), reflecting small airway
      flow obstruction. The pathophysiology of V/Q defects in asymptomatic asthmatic
      children warrants further investigation.

PMID- 12813202
TI  - Evaluating the changes in alveolar permeability and lung ventilation in patients
      with chronic renal failure after haemodialysis using 99mTc-DTPA radioaerosol
      inhalation lung scan.
AB  - Hypoxaemia occurring in patients with chronic renal failure (CRF) during
      haemodialysis (HD) has long been known. Several mechanisms of pathogenesis have
      been proposed. Before and after regular HD, lung ventilation (LV) and alveolar
      permeability (AP) were measured in 24 male patients with CRF (age, 61-75 years).
      LV and AP were determined by 99mTc-diethylenetriaminepentaacetic acid (99mTc
      DTPA) radioaerosol inhalation lung scan (99mTc-DTPA lung scan). The LV images
      were visually interpreted according to established criteria, including the
      presence or absence of an inhomogeneous distribution, inverted base to apex
      gradient and segmental hypoventilation. The degree of AP in the total right lung
      was presented as the clearance rate (K; %.min-1) of the time-activity curve from
      dynamic total right lung images. Ten male normal controls (age, 62-76 years) were
      enrolled in the study for comparison. Ten of 24 (42%) cases showed an
      inhomogeneous distribution and eight of 24 (33%) cases showed hypoventilation on
      equilibrium LV images. After regular HD for 5 h, no significant changes in the LV
      images were found. Before HD, the CRF patient group (K=1.14+/-0.36%.min-1) had a
      significantly faster clearance rate than that of normal controls (0.75+/
      0.14%.min-1, P<0.05). Moreover, the clearance rate after HD was significantly
      slower (0.87+/-0.15%.min-1, P<0.05) than that before HD. CRF can predispose
      patients to LV change and AP damage. After HD, the damage to AP is significantly
      improved. However, after HD, the change in LV is not significant.

PMID- 12813203
TI  - A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.
AB  - Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP)
      in metabolic and metastatic bone disease require the measurement of free tracer
      in plasma to derive the input function. We describe a simple method of
      determination of free 99mTc-MDP in vivo based on measurements of the ratio of the
      renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic
      acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared
      through the kidneys by glomerular filtration. Measurements of the fraction of
      free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal
      women enrolled in a study of the effect of hormone replacement therapy on the
      whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration
      rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA.
      The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663
      (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210
      min after injection. The results agreed closely with data using protein
      precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the
      biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540
      min for bound MDP. Highly significant relationships were found between the
      fraction of free MDP measured in each patient at each of the four time points and
      the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a
      larger value of K(total) was associated with a smaller fraction of free MDP.
      Multivariate regression analysis confirmed that this relationship held
      individually for both GFR and K(bone). A strong inverse relationship was found
      between K(total) and the plasma concentration of free 99mTc-MDP, but a much
      weaker relationship with the bound MDP concentration, a finding that is
      consistent with the slow re-equilibration of bound MDP in the circulation. The
      results confirm that the fraction of free 99mTc-MDP varies with time and shows
      significant differences between individuals, which are dependent on GFR and
      K(bone) amongst other factors.

PMID- 12813204
TI  - Third Leonard Berg Symposium: Neurobiology of the Aging Nervous System:
      introduction.

PMID- 12813205
TI  - The biology of aging in model organisms.

PMID- 12813206
TI  - Neurobiology of aging: hormonal regulation of development and longevity in C.
      elegans.

PMID- 12813207
TI  - Aging and hippocampal/cortical circuits in rodents.

PMID- 12813208
TI  - Impact of menopause on the brain.

PMID- 12813209
TI  - Aging and mammalian cerebral cortex: monkeys to humans.

PMID- 12813210
TI  - Delaying the mitochondrial decay of aging-a metabolic tune-up.

PMID- 12813211
TI  - Caloric restriction, gene expression, and aging.

PMID- 12813212
TI  - Aging, preclinical Alzheimer disease, and early detection.

PMID- 12813213
TI  - Detection of very early Alzheimer disease through neuroimaging.

PMID- 12813214
TI  - Amyloid-beta binding molecule: potential role in the pathogenesis and treatment
      of Alzheimer disease.

PMID- 12813215
TI  - Therapeutics and mild cognitive impairment: current status and future directions.

PMID- 12813216
TI  - Third Annual Leonard Berg Symposium: final thoughts and future directions.

PMID- 12813218
TI  - Full-spectrum proxy consent for research participation when persons with
      Alzheimer disease lose decisional capacities: research ethics and the common
      good.
AB  - This article focuses on riskier forms of research in Alzheimer disease (AD). It
      asks two fundamental questions. First, what is the upper threshold of potential
      risk that should be allowable in AD Research ("maximal potential risk")? Second,
      should proxy consent be permitted in higher-risk research even when there is no
      clear potential therapeutic value to the subject? There has been little
      discussion of maximal potential risk at a time when studies may be becoming
      increasingly invasive and risky. Proxy consent under such circumstances merits
      more thorough defense. This article discusses these questions on the basis of a
      "common good" ethic and calls for more input from researchers and the AD-affected
      constituency in resolving them.

PMID- 12813219
TI  - Surrogate decision-making and related issues.
AB  - This article discusses the role of surrogate decision-makers for persons who are
      cognitively impaired and cannot give informed consent. Questions raised follow.
      Is surrogate consent in research analogous to proxy consent in health care? What
      are some issues in surrogate consent? How does the risk-benefit ratio affect the
      consent process? What are the investigator's responsibilities regarding surrogate
      consent? Issues discussed include advance directives, durable power of attorney,
      legally authorized representatives, substituted judgment, double informed
      consent, responsibilities of surrogates, and barriers to informed consent. The
      article ends with recommendations to clarify state and national laws, change
      research designs, and establish a national mechanism for reviewing promising
      research that is usually prohibited.

PMID- 12813220
TI  - Consent and refusal in dementia research: conceptual and practical
      considerations.
AB  - This article discusses types of consent refusals, rates of refusal, factors that
      affect consent, and methods to increase rates of consent in elderly research
      participants and in those with dementia in particular. Refusals can be
      categorized according to several types: complete refusal, refusal that is time
      contingent, partial refusal, and contingent agreement. Rates of consent vary
      greatly across studies of persons with dementia. This variation can also be
      affected by different methodologies of calculating rates, in addition to
      differences in content of studies, populations, and procedures. To warrant
      consent, a study must first be scientifically sound, with a high likelihood of
      advancing knowledge, and must provide maximal protection to participants. Consent
      rates are affected by the following factors: levels of anticipated risks and
      benefits of the study, relationships among the different caregivers involved in
      the care of the potential subject, the ability of the researcher to properly
      identify and locate the person who needs to provide consent, characteristics and
      attitudes of the person providing consent, and the method of obtaining consent,
      including timing, location, method of presentation, and type of consent
      requested. An understanding of these issues can assist the researcher in
      tailoring research procedures so as to maximize rates of consent. It also raises
      ethical issues that warrant further discussion concerning the process of
      obtaining consent from and for persons with dementia.

PMID- 12813221
TI  - Sociocultural limits in informed consent in dementia research.
AB  - Ethical considerations in obtaining informed consent for dementia research have
      remained a largely neglected issue with respect to recruiting members of ethnic
      minorities and low-income groups. After briefly sketching the development of
      informed consent guidelines in the United States, this article focuses on the
      complex interactions between minority culture and low socioeconomic status as
      inhibiting factors in the informed consent process. We note that, at a minimum,
      freely given informed consent rests on the potential participant's belief that he
      or she is totally free to say "no." Suggestions are presented for making the
      informed consent more ethically constructive for members of socially underpowered
      populations.

PMID- 12813222
TI  - Federal regulatory, state statutory, and tort-based problems in research
      involving informed consent with Alzheimer disease and dementia patients.

PMID- 12813223
TI  - Publication of Cochrane Reviews in Critical Care Medicine and Pediatric Critical
      Care Medicine: guiding practice or duplicating the literature?

PMID- 12813224
TI  - Role of case reports in medical literature: bathwater has not been shown to
      cleanse babies.

PMID- 12813225
TI  - Dexamethasone and endotracheal reintubation rates: the answer is in the future,
      yet.

PMID- 12813226
TI  - Fulminant hepatitis A: liver transplantation or vaccination?

PMID- 12813227
TI  - Continuous positive airway pressure: performance of the prongs.

PMID- 12813228
TI  - Do specialist transport teams make a difference to the outcome of children with
      critical illness or injury?

PMID- 12813229
TI  - Is there a place for exogenous surfactant in mechanically ventilated infants with
      severe respiratory syncytial virus infection?

PMID- 12813230
TI  - Pediatric critical care medicine in Chinese--and other developments.

PMID- 12813231
TI  - Adrenal insufficiency in critical ill children: many unanswered questions.

PMID- 12813233
TI  - Weaning and extubation in infants and children: religion, art, or science.

PMID- 12813232
TI  - More, more, and even more beta2-adrenergic agents for treating acute asthma in
      children: is the "adrenergic approach" the only way?

PMID- 12813236
TI  - Can we assess quality of life for survivors of pediatric intensive care?

PMID- 12813238
TI  - Extracorporeal membrane oxygenation for pulmonary hemorrhage secondary to
      Wegener's granulomatosis?

PMID- 12813237
TI  - Is helium a better vehicle for aerosol therapy?

PMID- 12813239
TI  - Critical care for rare diseases.

PMID- 12813240
TI  - Some historic firsts for Pediatric Critical Care Medicine.

PMID- 12813241
TI  - Upper gastrointestinal bleeding in the pediatric intensive care unit: clinically
      important but questionably preventable.

PMID- 12813242
TI  - These are the good old days...these are the good new days.

PMID- 12813243
TI  - Partial liquid ventilation--the abyss between lab and clinic.

PMID- 12813244
TI  - Reply to "The etiology and outcome of pneumonia in HIV-infected children admitted
      to intensive care in a developing country: a commentary".

PMID- 12813245
TI  - The etiology and outcome of pneumonia in human immunodeficiency virus-infected
      children admitted to intensive care in a developing country: A commentary.

PMID- 12813246
TI  - Pediatric critical care: Global perspective.

PMID- 12813247
TI  - Microvascular thrombosis: What is the importance?

PMID- 12813248
TI  - Pulmonary artery catheters, children, and the twenty-first century.

PMID- 12813249
TI  - [In Process Citation]

PMID- 12813250
TI  - Introducing a new editor for Pediatric Critical Care Medicine: Patrick M.
      Kochanek, MD.

PMID- 12813251
TI  - Pediatric Critical Care Medicine, our expanding global mission.

PMID- 12813252
TI  - Lessons the "developing" and "developed" nations are learning about pediatric
      AIDS.

PMID- 12813253
TI  - Pulmonary fat embolism and intraosseous infusion.

PMID- 12813254
TI  - Heliox and high frequency oscillatory ventilation.

PMID- 12813256
TI  - Inodilator therapy in pediatric septic shock.

PMID- 12813255
TI  - CRIB: Clinical Risk Index for Bronchopulmonary Dysplasia?

PMID- 12813257
TI  - High-frequency ventilation in the pediatric intensive care unit.
AB  - OBJECTIVE: To provide a state-of-the-art review of high-frequency oscillatory
      ventilation in the management of pediatric patients with respiratory failure.
      DATA SOURCES: A thorough analysis of the preclinical and clinical literature
      regarding the pathophysiology of respiratory failure and the efficacy of high
      frequency techniques in the neonatal and pediatric populations. DATA SYNTHESIS:
      After an overview of the introduction of high-frequency techniques, the following
      topical areas are addressed: device vs. strategy, indications for use, disease
      specific strategies, additional practical considerations, and the future of high
      frequency techniques. CONCLUSIONS: The ideal ventilatory approach in patients
      with hypoxemic respiratory failure may be early institution of an "open lung"
      strategy using high-frequency ventilatory techniques. The mechanisms of gas
      exchange that are most important during high-frequency ventilation are bulk axial
      flow, interregional gas mixing, and molecular diffusion. Infants with hyaline
      membrane disease and congenital diaphragmatic hernia have also responded
      positively to the implementation of high-frequency techniques. The oxygenation
      index (mean airway pressure x Fio2 x 100/Pao2) provides useful prognostic
      information in patients being managed with high-frequency oscillatory ventilation
      and may help to identify those patients with high predicted mortality to offer
      additional or experimental therapies. In the future, the combination of high
      frequency oscillatory ventilation and partial liquid breathing offers the
      possibility of partitioning the physiologic changes associated with positive
      pressure ventilation. This approach may prove to be the ultimate lung-protective
      ventilatory strategy.

PMID- 12813258
TI  - Etomidate: applications in pediatric critical care and pediatric anesthesiology.
AB  - Etomidate is a carboxylated, imidazole-containing intravenous anesthetic agent
      introduced into clinical anesthesia practice in 1972. Its distinctive features
      that make it useful as an anesthetic induction include a lack of adverse effects
      on hemodynamic function as well as beneficial effects on cerebral blood flow and
      intracranial pressure. Because of these properties, its major role in anesthetic
      practice has been for the induction of anesthesia in patients with diminished
      cardiovascular function. As opposed to the considerable reported clinical
      experience with etomidate in the adult population, there remains limited reported
      information concerning its use in pediatric patients. This article reviews the
      specific end-organ effects of etomidate, the reports concerning its use in
      pediatric patients, and its adverse effect profile.

PMID- 12813259
TI  - Combined-modality therapy with inhaled nitric oxide and exogenous surfactant in
      term infants with acute respiratory failure.
AB  - OBJECTIVE: To report cases of neonates successfully treated with both exogenous
      surfactant and inhaled nitric oxide (INO). DESIGN: Retrospective chart review of
      full term infants treated between January and May 1999 in the neonatal intensive
      care unit of The Children's Hospital at Strong, University of Rochester,
      Rochester, New York. PATIENTS: Three full-term infants treated with surfactant
      and INO were identified. Each infant had severe acute respiratory failure (as a
      result of severe aspiration syndromes) and a clinical diagnosis of pulmonary
      hypertension and parenchymal lung disease in the absence of congenital
      malformations. INTERVENTIONS: One infant received INO (20-40 ppm) followed by
      exogenous surfactant (100mg/kg); the other two received surfactant followed by
      INO. MAIN RESULTS: All three infants exhibited a favorable response to treatment
      with these agents in terms of improved arterial oxygenation as summarized by
      oxygenation index and all survived to discharge home without referral for
      extracorporeal membrane oxygenation. CONCLUSIONS: No adverse interactions were
      observed related to INO plus surfactant therapy. The responses of these
      critically ill infants were consistent with the hypothesis that the actions of
      INO in dilating the pulmonary microvasculature and of exogenous surfactant in
      stabilizing and recruiting alveoli are complementary and may lead to additive
      clinical benefits. These case results suggest that more extensive clinical
      studies are warranted for combined-modality therapy with INO and exogenous
      surfactant in patients with the acute respiratory distress syndrome.

PMID- 12813260
TI  - Analysis of nonlinear volume-dependent respiratory system mechanics in pediatric
      patients.
AB  - OBJECTIVE: Analysis of dynamic respiratory system mechanics is generally based on
      a resistance-compliance model in which nonlinearities of the respiratory
      mechanics indices are not considered. The recently developed SLICE method
      analyzing consecutive volume slices of the tidal volume was used for
      determination of non-linear volume-dependent respiratory system mechanics. Volume
      dependent compliance C(Slice) and resistance R(Slice) were compared with C(MLR)
      and R(MLR) obtained by standard multiple linear regression analysis (MLR).
      DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit
      in a university hospital. PATIENTS: Fifteen pediatric patients, aged 24 days to
      9.6 yrs, weighing 3-67.5 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      With respect to their pulmonary status, the patients were grouped into three
      clinical groups: patients with no lung diseases, patients with restrictive lung
      diseases, and patients with obstructive lung diseases. All patients were
      mechanically ventilated via a cuffed endotracheal tube in the pressure-controlled
      mode. Flow and airway pressure were measured at the proximal end of the tube and
      tracheal pressure was continuously calculated. Respiratory mechanics were
      determined either with the SLICE method or, as reference, by using standard MLR.
      In most patients, the pressure-volume relationship was nonlinear, particularly in
      patients with restrictive and obstructive lung diseases. In the presence of
      considerable nonlinearity, the volume-dependent respiratory mechanics indices
      obtained by the SLICE method showed better agreement between recalculated and
      original pressure-volume loops compared with the MLR results. Furthermore, signs
      of overdistension of the patient's lung became obvious when using the SLICE
      method, whereas they were undetected by MLR. CONCLUSIONS: The SLICE method is
      well suited for the analysis of nonlinear volume-dependent respiratory system
      mechanics in pediatric patients. The SLICE method may be used as a first step
      toward an adaptation of ventilator settings with respect to the actual mechanical
      status of the patient's respiratory system, and, to prevent pulmonary
      overdistension.

PMID- 12813261
TI  - Evaluation of an opiate-weaning protocol using methadone in pediatric intensive
      care unit patients.
AB  - OBJECTIVE: To evaluate the efficacy of a standardized opiate-weaning protocol
      using methadone compared with methadone weaning before protocol development.
      DESIGN: Time series, prospective study with comparison to historical controls.
      SETTING: Twenty-bed medical-surgical intensive care unit in an academic
      children's hospital. PATIENTS: Ten children, aged 6 months to 18 yrs, who
      received methadone for weaning from continuous opiate infusions for >or=7 days
      compared with ten patients undergoing weaning by standardized protocol.
      INTERVENTIONS: Institution of standardized opiate-weaning protocol. MEASUREMENTS
      AND MAIN RESULTS: Patient age, gender, and diagnosis were similar in both
      nonprotocol (NP) and protocol (P) groups (p = NS). Days of opiate use were also
      similar between groups. Nine of ten NP and seven of ten P patients were on
      continuous fentanyl infusions, and the remainder were on continuous morphine
      infusions. P patients were weaned significantly faster than NP patients (median,
      9 days and 20 days, respectively; p <.001). P patients requiring short-term
      opiate use also weaned significantly faster than short-term NP patients (median,
      5 days and 21.5 days, respectively; p <.001). Withdrawal complications were seen
      in three NP patients with weaning delayed in two. Two P patients had withdrawal
      complications with no delay in weaning (p = NS). Significant methadone
      calculation discrepancy occurred in one NP patient but in no P patients.
      CONCLUSIONS: Pediatric intensive care unit patients requiring prolonged opiate
      use can be weaned by using methadone with minimal signs of withdrawal. Use of a
      standardized weaning protocol decreased time for weaning without increasing the
      frequency rate of withdrawal symptoms.

PMID- 12813262
TI  - Assessment of respiratory drive and muscle function in the pediatric intensive
      care unit and prediction of extubation failure.
AB  - BACKGROUND: Extubation failure can result from poor respiratory drive, impaired
      respiratory muscle function, or excessive inspiratory load. Measurement of airway
      pressure changes either during tidal breathing or after end-expiratory occlusion
      allows assessment of respiratory drive and muscle function. OBJECTIVE: To
      determine whether the results of airway pressure measurements characterized
      children who subsequently failed extubation and identify which test's results had
      the highest predictive performance. DESIGN: A prospective study. SETTING:
      Pediatric intensive care unit. PATIENTS: A sample of 42 stable intubated
      pediatric patients who were judged clinically ready for extubation. METHODS: A
      pneumotachograph was placed between the endotracheal tube and ventilator circuit.
      Airway pressure was measured from the pneumotachograph. The flow and pressure
      signals were amplified and displayed in real time on a laptop computer. During a
      temporary disconnection from the ventilator, the airway was occluded at end
      expiration and the occlusion maintained for at least five breaths. From the first
      inspiratory effort during the occlusion, the pressure generated after 0.1 sec of
      occlusion (P0.1) and the largest negative pressure (PI) were calculated. From the
      series of breaths during the occlusion, the maximum P0.1 (P0.1 max) and maximum
      PI (PI max) were determined and P0.1/P0.1 max, PI/PI max and P0.1/PI max
      calculated. From spontaneous, tidal breaths during ventilatory support the
      pressure time product was calculated. RESULTS: Thirty-six (84%) of the children
      were successfully extubated. The children who failed extubation were
      characterized by a lower median P0.1 (p <.06), P0.1/P0.1 max, p <.05 and P0.1/PI
      max (p <.02). P0.1 and P0.1/P0.1 max and performed best in predicting extubation
      failure (areas under the receiver operator characteristic curves, 0.76 and 0.77
      respectively). CONCLUSION: Assessment of P0.1 was the most useful airway pressure
      measurement in predicting extubation failure. Assessment of P0.1 may help to
      characterize children likely to fail extubation.

PMID- 12813263
TI  - Severity assessment in children hospitalized with bronchiolitis using the
      pediatric component of the Comprehensive Severity Index.
AB  - OBJECTIVE: Practice variation in the management of children hospitalized with
      bronchiolitis may result in significant differences in resource utilization.
      Determination of cost-effective care requires an objective means of adjusting for
      severity. We examined the correlation of the pediatric component of the
      Comprehensive Severity Index (CSI) with resource utilization in children
      hospitalized with bronchiolitis at ten children's medical centers. DESIGN:
      Demographics, clinical findings, laboratory results, interventions, and outcomes
      were retrospectively extracted from the charts of 804 consecutive children with
      International Classification of Disease, Ninth Revision codes for bronchiolitis
      from 10 children's medical centers. Comorbidities of prematurity, heart disease,
      and a prior history of wheezing or hospitalization, and the viral etiology of the
      illness were specifically examined. CSI scoring was performed at admission and
      maximum and correlated with patient variables and measures of resource
      utilization (hospital costs, length of stay, pediatric intensive care unit
      admission, and intubation). The performance of CSI relative to the Pediatric Risk
      of Mortality III was also evaluated. SETTING: Ten tertiary children's medical
      centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One child died and
      >99% of children returned to their baseline state of health. Admission CSI was
      comparable to the aggregate of all patient variables in its correlation with
      hospital costs (r2 = 0.23 vs. r2 = 0.24, respectively) and lengths of stay (r2 =
      0.23 vs. r2 = 0.24, respectively). Maximum CSI had the highest correlation
      coefficient with hospital costs (r2 = 0.42) and lengths of stay (r2 = 0.41),
      whereas the correlation of admission Pediatric Risk of Mortality III scores with
      costs was r2 = 0.12 and with lengths of stay was r2 = 0.07. CSI scores also
      correlated well with measures of resource utilization in subgroups of
      bronchiolitis patients with comorbidities or other risk factors for severe
      disease. CONCLUSIONS: CSI scores correlate well with resource use in pediatric
      patients hospitalized with bronchiolitis. This severity scoring system may be
      useful in assessing the cost-effectiveness of their care.

PMID- 12813264
TI  - Relevance of diagnostic diversity and patient volumes for quality and length of
      stay in pediatric intensive care units.
AB  - OBJECTIVE: Investigation of associations of the diagnostic diversity and volumes
      with efficiency and quality of care. DESIGN: Prospective observational study.
      SETTING: Thirty-two pediatric intensive care units (PICUs), 16 selected by random
      cluster sampling, and 16 volunteering. PATIENTS: Consecutive admissions of 11,165
      patients. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were length of
      PICU stay (LOS) and mortality rate, adjusted by generalized linear regression and
      multivariate logistic regression, respectively. Each diagnosis was categorized
      into 21 predefined, mutually exclusive categories. Diagnostic diversity of each
      PICU was characterized by an information-theoretical measure (entropy). For a
      patient-level analysis, the associations of this measure and PICU patient volume
      with outcomes were using regression models. For an institution-level analysis,
      the outcome measures of each PICU were adjusted using ratios of
      observed/predicted (by the regression models) values, and the associations of
      these ratios with diagnostic diversity and patient volume were investigated using
      linear bivariate regressions. Diagnostic diversity ranged in the PICUs from 0.823
      to 0.928, when standardized to the uniform distribution with entropy of 1.
      Congenital heart diseases (12.6%) head traumas (11.5%), other central nervous
      system conditions (9.7%), and pneumonias (8.7%) constituted the largest
      diagnostic categories. Patient-level analysis indicated that longer adjusted LOS
      was associated with larger diagnostic diversity (p <.0001) and lower admission
      volumes (p <.0001). However, for a given increase in diagnostic diversity, a
      large LOS increase was associated with low-volume, but not high-volume units.
      Severity-adjusted mortality rates were inversely related (p =.036) only with
      admission volumes, but not diagnostic mix. Institution-level standardized LOS
      ratios correlated with diagnostic diversity (r2 = 0.145; p =.031). Institution
      level standardized mortality ratios were inversely related (r2 = 0.123; p =.049)
      with admission volumes. CONCLUSIONS: Patient volumes encountered in a PICU are
      important for maintaining quality and efficiency of care. In low-volume units,
      fewer diagnoses and higher volumes were both associated with higher efficiencies.
      In high volume units, diagnosis-specific volumes were generally large enough for
      achieving diagnosis-independent efficiency. Diagnostic mix was not associated
      with PICU mortality ratios, but higher PICU volumes were associated with lower
      mortality rates.

PMID- 12813265
TI  - Meter-dosed, inhaled beclomethasone initiated at birth to prevent
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: To examine the hypothesis that meter-dosed, inhaled beclomethasone
      administered to premature infants, beginning at birth and continuing in a
      tapering dosage schedule over the first 12 days of life, decreases the occurrence
      of bronchopulmonary dysplasia (BPD), at 36 wks corrected gestational age. DESIGN:
      Prospective, randomized, double-blind, placebo-controlled, small pilot clinical
      trial. SETTING: Tertiary care, neonatal intensive care unit. PATIENTS: Premature
      low birth weight neonates (<or=1300 g) followed from birth until 36 wks corrected
      gestational age. INTERVENTIONS: Aerosolized beclomethasone dipropionate was
      administered in a tapering dosage schedule beginning at birth and extended for
      the first 12 days of life, utilizing an aerosol spacer chamber and manual hand
      ventilation. In a subset of the subjects, a cosyntropin stimulation test was
      conducted on day 13 to ascertain potential hypothalamic-pituitary-adrenal axis
      suppression. Need for mechanical ventilation/continuous positive airway pressure
      (CPAP) and/or oxygen was assessed at 30 days of life and 36 wks corrected
      gestational age in addition to a number of other variables clinically relevant to
      the development of BPD. MEASUREMENTS AND MAIN RESULTS: In total, 19 placebo
      treated and 20 beclomethasone-treated infants completed the study. Inhaled
      beclomethasone significantly reduced the need for supplemental oxygen at 30 days
      (p =.005) of life but not at 36 wks corrected gestational age (p =.243). A
      significantly greater proportion of infants receiving beclomethasone were
      extubated before 2 wks of age (p =.035), and infants receiving beclomethasone
      required significantly fewer days of mechanical ventilation (p =.004), but
      increased days of nasal CPAP as compared with the control group. Although fewer
      beclomethasone-treated than placebo-treated infants were administered intravenous
      steroids after 2 wks of age, this difference was not significant. No differences
      between groups were noted for the diagnoses of retinopathy of prematurity,
      nosocomial infection, or intraventricular hemorrhage. Similarly, no differences
      in the cosyntropin stimulation test were ascertained between treated and
      nontreated infants. No adverse effects were attributable to inhaled
      beclomethasone. CONCLUSIONS: In this small series, inhaled beclomethasone
      initiated at birth did not reduce the occurrence of BPD as defined by the
      continued requirement for supplemental oxygen at 36 wks corrected gestational
      age. However, inhaled beclomethasone did reduce the need for supplemental oxygen
      at 30 days of life and appeared to facilitate the transition from
      intubation/mechanical ventilation to less invasive nasal CPAP, as demonstrated by
      more frequent extubation before 2 wks of age and decreased total duration of
      mechanical ventilation in the beclomethasone-treated group. No adverse effects,
      including adrenal suppression, were noted in infants treated with inhaled
      beclomethasone. On the basis of the safety and apparent effectiveness of early
      inhaled beclomethasone in reducing the need for invasive mechanical ventilation
      and supplemental oxygen during the first month of life in premature infants, a
      larger clinical trial with greater power is warranted to ascertain if early
      inhaled beclomethasone can attenuate the occurrence of BPD.

PMID- 12813266
TI  - Myocardial injury in children with respiratory syncytial virus infection.
AB  - OBJECTIVE: Respiratory syncytial virus (RSV) infection is associated with a
      number of extrapulmonary manifestations, including a sepsis-like syndrome
      characterized by any combination of hypothermia, fever, apnea, hypovolemia, and
      myocardial dysfunction. We hypothesized that RSV can have a direct injurious
      effect on the myocardium of infants and children that can be detected by the
      presence of cardiac troponin I (cTnI), a highly sensitive and specific marker of
      myocardial injury, in the blood of patients infected with the virus. DESIGN:
      Serial cTnI measurements were obtained from patients admitted with documented RSV
      infection to the pediatric intensive care unit (PICU). PARTICIPANTS: Data were
      collected and analyzed from 22 RSV infected patients and 11 control patients.
      RESULTS: Elevated levels of cTnI were detected in 54.5% (12/22) of the study
      population during their PICU admission. The average cTnI level was significantly
      higher in the RSV infected group than in controls. There was a significant
      association between the presence of a positive troponin assay and the occurrence
      of a cardiovascular event, the need for inotropic support, and the requirement of
      mechanical ventilation. Patients who required inotropic support had a
      significantly higher cTnI level than the rest of the study population.
      CONCLUSION: A large percentage of children admitted to the PICU with RSV
      infection have myocardial damage as detected by the use of commercially available
      troponin assays. Additionally, in a portion of these patients, this damage is
      clinically significant, leading to cardiovascular instability and the need for
      inotropic support.

PMID- 12813267
TI  - Validation of a blind transpyloric feeding tube placement technique in pediatric
      intensive care: rapid, simple, and highly successful.
AB  - OBJECTIVE: Nasogastric feeding in intensive care is poorly tolerated as a result
      of gastroparesis. Transpyloric (TP) feeding has been limited by difficulty in
      tube placement. This study was to independently validate the success rate of a
      previously published bedside TP feeding tube (FT) placement technique. DESIGN:
      Prospective interventional study. SETTING: Tertiary pediatric intensive care unit
      (PICU) in a university hospital. PATIENTS: Children whose intensivist requested
      TP feeding, and who were without known fundoplication, pharyngeal trauma, or
      gastric ulceration. INTERVENTIONS: After informed consent, an unweighted
      polyurethane feeding tube with a flexible wire stylet was inserted using a
      standard technique with metoclopramide, right lateral position, and air
      insufflation during advancement until <2 mL air could be aspirated after
      insufflation of 5-10 mL air. The tubes were inserted by one of the authors, whose
      training was only to observe one insertion, then perform one insertion with
      supervision. MEASUREMENTS AND MAIN RESULTS: Patient demographics, procedural
      data, and success rate based on radiography were prospectively recorded. There
      were 71 insertions on 38 patients from February 1999 to October 1999. Patients
      were aged 56 +/- 69.8 months, weighed 17.8 +/- 18 kg, 69% were ventilated, and
      56% received procedural sedation. Success rate for TP-FT placement was 63/71
      insertions (88.7%) in an average of 7.43 +/- 6.85 mins (median, 5 mins; range, <1
      45 mins); of 38 patients, 36 had a successful TP- FT (95%). Insertion was well
      tolerated. Of the successful TP-FTs, on day 1 (n = 63) the FT was in distal
      duodenum or jejunum in 51% and by days 3-5 (n = 51), this increased to 75%.
      CONCLUSIONS: Bedside placement of a TP-FT with this technique is simple, rapid,
      well tolerated, and highly successful with little training. Immediate radiograph
      to confirm TP placement may not always be necessary. In our experience, this
      technique has obviated the need to search for another method to achieve a
      transpyloric feeding tube.

PMID- 12813268
TI  - Organ donation in children: role of the pediatric intensive care unit.
AB  - OBJECTIVES: Children waiting for organ transplants continue to die because of the
      shortage of available organs. Studies of organ donation in children are scarce.
      The evaluation of the organ donation experience in a pediatric tertiary care
      hospital may identify factors that influence actual organ donation rates and lead
      to strategies to improve pediatric organ donation. DESIGN: Retrospective study.
      SETTING: Pediatric intensive care unit in a Canadian pediatric referral center.
      PATIENTS: All children with brain death over an 8-yr period (1990-1997).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 199 children who fulfilled
      the criteria for brain death, 153 were medically suitable for organ donation.
      Families were approached for consent to organ donation in 128 (84%) of the 153
      suitable cases. Consent was obtained in 63% (81/128) of those asked. Brain death
      caused by acute neurosurgical lesions was highly correlated to medical
      suitability and consent. Families identified as ethnic minorities were
      significantly more likely to refuse. After consent was granted, organs were
      procured from 63 (78%) of 81 donors, for an average of 3.6 organs transplanted
      per donor. There was a failure to procure organs in 22% (18/81) of cases after
      consent had been granted, primarily as a result of cardiocirculatory instability
      while in the intensive care unit. CONCLUSIONS: Despite an encouraging 63% consent
      rate for organ donation when families are approached, only 41% of potential
      donors proceeded to actual donation. Strategies for a prospective pediatric study
      should focus on mandatory request, multicultural issues, and aggressive
      postconsent medical management and procurement. The pivotal role of the pediatric
      intensive care unit practitioner should be emphasized.

PMID- 12813269
TI  - Venoarterial extracorporeal membrane oxygenation impairs basal nitric oxide
      production in cerebral arteries of newborn lambs.
AB  - OBJECTIVE: Based on previous studies in our laboratory showing that exposure of
      newborn lambs to venoarterial extracorporeal membrane oxygenation (ECMO) alters
      cerebral blood flow autoregulation, we postulated that this altered vascular
      reactivity is mediated through changes in endothelial function caused by the
      pumping systems used in venoarterial ECMO. We tested that hypothesis in this
      study. DESIGN: Prospective, controlled, laboratory trial. SETTING: Animal
      research laboratory. SUBJECTS: Two groups of newborn lambs. INTERVENTIONS: One
      group of animals was exposed to venoarterial ECMO (n = 6) and another group of
      control animals (n = 5) was maintained under similar conditions for 2 hrs on the
      ventilator without ECMO. MEASUREMENTS AND MAIN RESULTS: Third-order branches of
      the middle cerebral arteries (140-300 microm diameter) were isolated from animals
      at the end of the experiment, mounted on glass cannulae in an arteriograph, and
      superfused with Krebs-Ringer buffer. Decrease in the diameter of the arteries
      induced by exposure of the vessels to nitric oxide synthase inhibitor NG-nitro-L
      arginine methyl ester (200 micromol/L) for 30 mins was significantly less (p
      <.05) in arteries from lambs exposed to ECMO compared with control animals. There
      were no significant differences between the two groups in myogenic response or in
      the contractile activity of the arteries to increasing concentrations of
      serotonin. CONCLUSIONS: These results demonstrate that 2 hrs of exposure of
      newborn lambs to venoarterial ECMO leads to a decrease in basal production of
      nitric oxide in cerebral arteries, and suggest that venoarterial ECMO selectively
      impairs cerebral arterial endothelial function.

PMID- 12813270
TI  - Effect of nitric oxide and high-frequency oscillatory ventilation in meconium
      aspiration syndrome.
AB  - OBJECTIVE: To test the hypothesis that inhaled nitric oxide, when combined with
      high-frequency oscillatory ventilation, is an effective therapeutic agent in
      meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING:
      The animal research laboratory at The Children's National Medical Center.
      SUBJECTS: Five newborn piglets, 1-2 wks old, weighing 3.6 +/- 0.2 kg.
      INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated.
      Catheters were placed in the femoral vein and artery and the pulmonary artery.
      After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was
      insufflated into the lungs. Animals were ventilated with a SensorMedics
      oscillator to maintain arterial blood gases in a normal range (pH, 7.35-7.45;
      Paco2, 40-45 mm Hg [5.3-6.0 kPa]; Pao2, 70-90 mm Hg [9.3-12.0 kPa]). Ventilator
      settings were increased as needed until maximum settings as follows: Fio2, 1.00;
      proximal oscillatory pressure amplitude, 36 cm H2O; mean airway pressure, 25 cm
      H2O; frequency, 10 Hz. After a short period of stabilization, inhaled nitric
      oxide was administered. Concentrations of 40, 20, and 10 ppm were given and
      measurements were taken after each exposure to inhaled nitric oxide and after its
      discontinuation. To assure that there was no additive effect of inhaled nitric
      oxide, each dose was given for 20 mins followed by a 15-min normalization period
      at 0 ppm. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory
      settings, arterial blood gases, and methemoglobin were recorded at each study
      period. Measurements were taken after each exposure to inhaled nitric oxide and
      after its discontinuation. Arterial saturation and partial pressure of arterial
      oxygen (Pao2) were significantly lower after meconium aspiration when compared
      with baseline. Administration of inhaled nitric oxide improved oxygenation
      without a significant decrease in pulmonary artery pressure. CONCLUSION: In this
      model of meconium aspiration syndrome, short-term exposure to inhaled nitric
      oxide when combined with high-frequency oscillatory ventilation improved
      oxygenation secondary to better distribution of inhaled nitric oxide. The
      increase in oxygenation may be secondary to improved ventilation perfusion
      mismatch, as the primary etiology of hypoxia in this model may be a combination
      of parenchymal lung disease and pulmonary hypertension.

PMID- 12813272
TI  - A student, a nun, and a professor.

PMID- 12813271
TI  - Comparison of work of breathing between two neonatal ventilators utilizing a
      neonatal pig model.
AB  - OBJECTIVE: The purpose of this study was to determine whether variations in the
      delivery systems of continuous positive airway pressure between two ventilators
      would lead to differences in patient work of breathing (WOBp). DESIGN: Comparison
      of two neonatal ventilators with a neonatal pig model. SETTING: Animal
      laboratory. SUBJECTS: Thirty healthy, intubated, sedated, spontaneously breathing
      neonatal piglets weighing 1.0-2.0 kg. INTERVENTIONS: Patient work of breathing
      (WOBp) (gm cm/kg) was measured by using measurements based on an esophageal
      balloon and a flow transducer. Each breath was analyzed for ventilator response
      times (in msecs) and negative deflection of pressure. Each animal was studied
      with the Siemens SV300 and Drager Babylog 8000, on continuous positive airway
      pressure settings of 0, 3, and 5 cm H2O. Data were analyzed by using Wilcoxon's
      Signed Rank Test with significance of p <or=.05. MEASUREMENTS AND MAIN RESULTS:
      Comparing ventilators, WOBp was on average 29% higher in the Babylog. Analysis of
      individual breaths showed that disparity in WOBp was probably related to the
      automatic availability of 2 cm H2O pressure support ventilation in the SV300.
      This may also explain the differences in delay time during the start of the
      inspiratory phase before initiation of gas flow. The mean duration of inspiratory
      effort was 394 (+/- 157) msecs in the Babylog and 138 (+/- 35) msecs in the
      SV300, a 174% increase in time delay for the Babylog (p =.005). During
      inspiratory effort, there was >1 cm H2O negative pressure before flow was
      available with the Babylog. CONCLUSIONS: In intubated patients, maximum energy
      expenditure occurs at the initiation of ventilator breaths. WOBp in neonatal pigs
      was significantly increased. The response time of the ventilators may explain the
      differences in initiation of flow times and patient work. These differences may
      have important implications for energy kinetics, weight gain, and duration of
      mechanical ventilation in preterm neonates.

PMID- 12813273
TI  - End-of-life decision-making and satisfaction with care: parental perspectives.
AB  - OBJECTIVES: To evaluate parents' perceptions of the process by which decisions
      are made to limit or withdraw life support from critically ill children, and to
      evaluate parents' perceptions of their child's death in the pediatric intensive
      care unit (ICU) and their satisfaction with the care provided. DESIGN: Survey.
      SETTING: University teaching hospital. PARTICIPANTS: Seventy-eight parents who
      experienced the death of a child in the ICU between January 1, 1995 and June 30,
      1998. INTERVENTIONS: Structured telephone interviews. MEASUREMENTS AND MAIN
      RESULTS: Forty-one parents recalled discussing the limitation or withdrawal of
      life support from their child with a physician. Of these, 31 (76%) felt they had
      just the right amount of authority to make decisions for their child, 8 (20%)
      felt they had too little, and 1 (2%) felt they had too much. Those satisfied with
      their decision-making authority had more trust in their physician than those who
      were dissatisfied (5 vs. 1, p <.001 by Mann-Whitney U test, where 1 = no trust
      and 5 = complete trust). Factors identified by parents as being extremely
      important in the decision-making process included physician recommendations,
      diagnosis, expected neurologic recovery, and degree of pain and suffering. A
      total of 51 parents were with their child at the time of death. Although none
      regretted being present, 17 parents who were not present later wished they had
      been (p <.001, Fisher's exact test). The quality of care provided to parents by
      the ICU staff was graded (1 = poor; 5 = excellent). Eleven parents (14%) scored
      quality of care <or=2. These parents more often had a child die of an acute
      illness (6/11 vs. 8/67; p <.01), more often felt uninformed about their child's
      condition (9/11 vs. 19/67; p <.001), were less likely to understand the cause of
      death (4/11 vs. 51/67; p <.01) and less likely to have contact with hospital
      staff at home after the child's death (6/11 vs. 56/66; p <.05). These parents
      were also less likely to perceive staff as sympathetic (4/11 vs. 57/67; p <.001)
      or kind (5/11 vs. 65/67; p <.001). CONCLUSIONS: Recommendations of physicians,
      nature of illness and expected neurologic recovery are important to parents
      making end-of-life decisions for their children. The establishment of trust is
      crucial in guiding parents through the decision-making process. Parental presence
      at the time of a child's death, the provision of adequate information, and a
      sympathetic environment may facilitate a healthy grief response.

PMID- 12813274
TI  - Whose journal is it anyway? A new journal, a new paradigm?

PMID- 12813276
TI  - Predicting costs in the intensive care unit.

PMID- 12813275
TI  - Practice makes perfect.

PMID- 12813278
TI  - Pediatric Critical Care Medicine: Another member of the critical care family.

PMID- 12813279
TI  - Coming of age.

PMID- 12813280
TI  - Biochemical, cellular, and molecular mechanisms in the evolution of secondary
      damage after severe traumatic brain injury in infants and children: Lessons
      learned from the bedside.
AB  - OBJECTIVE: To present a state-of-the-art review of mechanisms of secondary injury
      in the evolution of damage after severe traumatic brain injury in infants and
      children. DATA SOURCES: We reviewed 152 peer-reviewed publications, 15 abstracts
      and proceedings, and other material relevant to the study of biochemical,
      cellular, and molecular mechanisms of damage in traumatic brain injury. Clinical
      studies of severe traumatic brain injury in infants and children were the focus,
      but reports in experimental models in immature animals were also considered.
      Results from both clinical studies in adults and models of traumatic brain injury
      in adult animals were presented for comparison. DATA SYNTHESIS: Categories of
      mechanisms defined were those associated with ischemia, excitotoxicity, energy
      failure, and resultant cell death cascades; secondary cerebral swelling; axonal
      injury; and inflammation and regeneration. CONCLUSIONS: A constellation of
      mediators of secondary damage, endogenous neuroprotection, repair, and
      regeneration are set into motion in the brain after severe traumatic injury. The
      quantitative contribution of each mediator to outcome, the interplay between
      these mediators, and the integration of these mechanistic findings with novel
      imaging methods, bedside physiology, outcome assessment, and therapeutic
      intervention remain an important target for future research.

PMID- 12813281
TI  - Review of the methodologies and applications of scoring systems in neonatal and
      pediatric intensive care.
AB  - Scoring systems and risk prediction rules quantitate the severity of clinical
      conditions and stratify patients according to a specified outcome. In intensive
      care medicine, the complexity and number of clinical scoring systems is
      increasing as their utility in both health services research and clinical
      medicine broadens. We anticipate that with increasing healthcare costs and
      competition, the demand for risk adjusted outcomes and institutional benchmarking
      will increase. As academicians and clinicians, it is vital to be knowledgeable
      regarding the methodologies and applications of these scoring and risk prediction
      systems to ensure their quality and appropriate utilization.

PMID- 12813282
TI  - Comparison of predictors of extubation from mechanical ventilation in children.
AB  - OBJECTIVE: Unsuccessful extubation from mechanical ventilation increases
      mortality and morbidity. Therefore, the identification of an accurate predictor
      of successful extubation is desirable. This study was designed to determine
      whether the results of easily performed respiratory measurements, particularly if
      reported as "combined extubation" indices, were better predictors of extubation
      failure in a pediatric population than were readily available clinical data.
      DESIGN: Prospective observational study. SETTING: Tertiary pediatric intensive
      care unit. PATIENTS: All children who required mechanical ventilation for >/=24
      hrs during a 12-month period and whose parents gave informed written consent.
      INTERVENTIONS: Respiratory function measurements were made (on average) 7 hrs
      (range, 0.2-25.0 hrs) before extubation. Arterial blood gas results were obtained
      immediately before extubation. The values of each predictor associated with
      maximum sensitivity and specificity were determined, and the areas under receiver
      operator characteristic curves were compared to determine the most accurate
      predictor of successful extubation. MEASUREMENTS AND MAIN RESULTS: A total of 47
      children (mean age, 3.90 yrs; range, 0.10-17.3 yrs) were studied; extubation
      failed in 7. A low tidal volume (<7.5 mL/kg) and a low minute volume (<250 mL/kg)
      had the highest sensitivities (86% and 71%, respectively) and specificities (61%
      and 71%, respectively) in predicting extubation failure. The a/A ratio performed
      least well in predicting extubation failure (area under the receiver operating
      characteristic curve, 0.51). CONCLUSIONS: Volume measurements during pediatric
      mechanical ventilation may facilitate successful extubation.

PMID- 12813283
TI  - Heliox improves ventilation during high-frequency oscillatory ventilation in
      pediatric patients.
AB  - OBJECTIVE: To describe improved ventilation during high-frequency oscillatory
      ventilation when a nitrogen-oxygen gas mixture is replaced by a helium-oxygen gas
      mixture. DESIGN: Case series. SETTING: A tertiary pediatric intensive care unit.
      PATIENTS: Five patients with hypoxemic respiratory failure who developed
      persistent respiratory acidosis during treatment with high-frequency oscillatory
      ventilation. INTERVENTIONS: Introduction of helium-oxygen into a conventional
      high-frequency oscillatory ventilation circuit. MEASUREMENTS AND MAIN RESULTS:
      Blood gas values (pH, Pco2, and Po2) were compared in these patients during
      treatment with high-frequency oscillatory ventilation with nitrogen-oxygen gas
      flow and then for several hours after a change in treatment to helium-oxygen gas
      flow. An initial 24% decrease in Pco2 was documented, and an ultimate 43%
      decrease in Pco2 was observed. The mechanism for this improved ventilation may be
      related to improved gas flow properties as well as increased CO2 diffusion
      resulting from helium's low-mass density. Oxygenation was not adversely affected
      in any way. CONCLUSION: In patients with hypoxemic respiratory failure and in
      whom respiratory acidosis develops during high-frequency oscillatory ventilation,
      the use of helium-oxygen rather than nitrogen-oxygen may improve ventilation and
      decrease ventilator-related trauma. Further investigation is needed to validate
      these findings and to elucidate the mechanisms of improved ventilation.

PMID- 12813284
TI  - Hypoxic gas therapy using nitrogen in the preoperative management of neonates
      with hypoplastic left heart syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of hypoxic gas therapy using nitrogen, where
      the fraction of inspired oxygen (Fio2) was reduced to <0.21 in patients with
      univentricular parallel circulation. DESIGN: Case report. SETTING: A pediatric
      intensive care unit at a university hospital. PATIENTS: Two neonatal patients
      with hypoplastic left heart syndrome admitted to the pediatric intensive care
      unit preoperatively. INTERVENTIONS: Nitrogen insufflation by using continuous
      flow respiratory support. MEASUREMENTS AND MAIN RESULTS: We reduced the Fio2 in
      these patients by giving additional nitrogen to relieve pulmonary overcirculation
      and systemic hypoperfusion suspected by transcutaneous arterial oxygen saturation
      >90%, systemic arterial hypotension, and low urine output in the preoperative
      course. The improvement of systemic hemodynamics concomitant with decreases in
      transcutaneous arterial oxygen saturation <85% was accomplished by controlling
      Fio2 between 0.14 and 0.18. These infants were able to undergo Norwood's surgery
      after several days without complications relating to Fio2 reduction. CONCLUSION:
      Hypoxic gas therapy with nitrogen was effective clinically in preventing
      pulmonary overcirculation in neonatal patients with univentricular and parallel
      circulation.

PMID- 12813285
TI  - Predicting pediatric length of stay and acuity of care in the first ten minutes
      with artificial neural networks.
AB  - OBJECTIVE: To evaluate the efficacy of artificial neural networks in categorizing
      pediatric trauma patients into four distinct acuity of care groups and in
      determining the length of stay (LOS) within specific areas of the hospital.
      DESIGN: Using historical information from >8,000 pediatric trauma patient
      records, train and evaluate artificial neural networks to predict the injury
      severity and LOS for each patient in pediatric intensive care units (PICUs), step
      down units, and floor units. Each artificial neural network is evaluated for
      categorization accuracy and mean absolute error difference on the predicted LOS.
      SUBJECTS: A total of 10,353 patient records from the National Pediatric Trauma
      registry, representing all pediatric trauma patients treated at affiliated
      hospitals from April 1994 through December 1996. Records with incomplete
      information were eliminated from the study, leaving 8,081 usable patient records.
      MEASUREMENTS: A total of 14 variables are selected from the 81 values present in
      the National Pediatric Trauma Registry as independent variables for the
      artificial neural networks. Each neural network produces nine output values: five
      for categorizing the patient's injury severity, three for the LOS in the PICU,
      step-down unit, and floor units, and one for the patient's total LOS. RESULTS: A
      fuzzy ARTMAP neural network accurately categorizes 88% of mortality patients and
      58.3% of critical PICU patients. A backpropagation neural network succeeded in
      predicting the total LOS to within 1 day for 51.4% and the ICU LOS to within 1
      day for 70.4% of all evaluated patients. CONCLUSION: Information available in the
      first 10 mins of a patient's presentation at the emergency room can be used by an
      artificial neural network to predict injury severity and LOS. Artificial neural
      networks enable more effective resource planning and patient management.

PMID- 12813286
TI  - Use of the Pala-nate device in the prevention of palatal grooves in premature,
      intubated infants.
AB  - OBJECTIVE: Previous studies demonstrated that the use of a custom-made intraoral
      acrylic appliance, known as a palatal stabilizing device, prevents palatal groove
      formation and reduces the frequency rate of accidental extubations in premature,
      intubated babies. In this study, we compared the effectiveness of a prefabricated
      palatal device with an acrylic custom-made palatal stabilizing device.
      Specifically, we compared the stability, fit, and retention of these two devices.
      DESIGN: Randomized comparative study. SETTING: Clincal trial. PATIENTS: A total
      of 70 medically stable, premature, intubated babies. INTERVENTIONS: A total of 70
      medically stable, premature, intubated babies randomly received Pala-nate
      (experimental group, n = 34) or palatal stabilizing device (control group, n =
      36). MEASUREMENTS AND MAIN RESULTS: Differences among birth weight, gestational
      age, and period of intubation of the two groups were statistically nonsignificant
      at p </=.05. Although both appliances were effective in the prevention of palatal
      grooves, the Pala-nate was less retentive, thus requiring greater monitoring, and
      it was associated with a larger number of accidental extubations. The differences
      between the two groups were statistically significant at p </=.05. CONCLUSIONS:
      We concluded that the custom-made, acrylic, palatal stabilizing device was more
      stable and more effective in the prevention of spontaneous extubations in
      premature orally intubated infants.

PMID- 12813287
TI  - Hemophagocytic lymphohistiocytic syndrome: Unrecognized cause of multiple organ
      failure.
AB  - OBJECTIVE: To describe an often-unrecognized clinical picture of multiple organ
      failure in hemophagocytic lymphohistiocytic syndrome (HLS). DESIGN: Retrospective
      chart review. SETTING: A ten-bed pediatric intensive care unit (PICU) in a
      tertiary children's university hospital. PATIENTS: A total of 11 children (age, 5
      months to 13 yrs) who fulfilled the criteria for the diagnosis of familial- or
      infectious-associated hemophagocytic lymphohistiocytosis and who required
      intensive care support for organ failure. INTERVENTION: None. MAIN RESULTS:
      During a 10-yr period, 5,439 children were hospitalized in our PICU. A total of
      11 children were diagnosed as suffering with HLS. Of these 11 patients, three
      (27%) had the familial form and eight had the infectious-associated form. After
      admission to the PICU, seven patients (63%) were diagnosed as suffering with HLS
      and each had one or more organ failures (patients 3-7, 9, and 10). All presented
      with fever, hepatomegaly, and splenomegaly; in addition, all had at least two of
      the following: anemia, neutropenia, or thrombocytopenia. All 11 had
      lymphohistiocytic accumulation in bone marrow (n = 10), lymph node (n = 2), lung
      (n = 2), and/or liver (n = 1). Organ failure was noted most often in the
      respiratory system (n = 7) attributable to severe, acute respiratory distress
      syndrome and pleural effusion. Of the 11 patients, six had cardiovascular
      involvement that manifested as shock in three and as capillary leak syndrome in
      three. Renal failure occurred in four patients. Of these, two required
      hemodiafiltration and one required peritoneal dialysis. Liver failure occurred in
      three and central nervous system involvement and coma in three. Most of the
      patients required massive therapeutic intervention, including assisted
      ventilation (n = 6), inotropic support (n = 3), and hemofiltration (n = 3). A
      total of seven patients (63%) died. CONCLUSIONS: Hemophagocytic lymphohistiocytic
      syndrome in the pediatric population may have a dramatic clinical picture, with
      multiple organ failure as a presenting symptom or early in the disease course,
      mandating intensive support in the PICU.

PMID- 12813288
TI  - Isoflurane therapy for status asthmaticus in children: A case series and
      protocol.
AB  - OBJECTIVE: To describe the use of inhaled isoflurane by using a standardized
      protocol in the treatment of respiratory failure secondary to status asthmaticus
      in a series of pediatric patients. DESIGN: Case series. SETTING: Pediatric
      intensive care unit of a tertiary care military medical facility. PATIENTS: Six
      pediatric patients ranging in age from 14 months to 15 yrs who were treated with
      isoflurane in our pediatric intensive care unit for status asthmaticus from 1995
      to 1998. INTERVENTION: Inhaled isoflurane therapy was initiated by using the
      treatment protocol after the patients had failed conventional medical management
      in the treatment of their asthma. MEASUREMENTS AND MAIN RESULTS: All patients
      tolerated isoflurane therapy well by using our standardized protocol in
      conjunction with careful hemodynamic monitoring and support. The administration
      of inhaled isoflurane resulted in measurable improvements in the subject
      patients, as evidenced by statistically significant decreases in Paco2 and peak
      inspiratory pressures, as well as a significant increase in pH. All six patients
      were successfully extubated and were discharged from the hospital without
      apparent sequelae. CONCLUSIONS: We conclude isoflurane may be a safe, effective
      treatment modality in the management of status asthmaticus refractory to
      aggressive medical therapy, although further study is warranted. We emphasize
      this mode of therapy should be instituted only after traditional treatment
      modalities have failed and appropriate intensive care support is available.

PMID- 12813289
TI  - Comparison of plasma levels and pharmacodynamics after intraosseous and
      intravenous administration of fosphenytoin and phenytoin in piglets.
AB  - OBJECTIVE: To compare plasma drug levels and pharmacodynamics of fosphenytoin or
      phenytoin when given intraosseously or intravenously in doses relevant to
      children. DESIGN: Prospective controlled randomized study. SETTING: University
      hospital animal laboratory. SUBJECTS: A total of 40 mixed-breed piglets (age, 4-6
      months; weight, 20-40 kg). INTERVENTIONS: The animals were anesthetized, after
      which they underwent intubation, instrumentation, and mechanical ventilation. A
      central venous catheter and an arterial catheter were placed for monitoring and
      blood sampling. A peripheral intravenous catheter with a 15-gauge intraosseous
      needle was inserted for drug infusion. A total of 40 animals (ten per group) were
      randomly assigned to receive intravenous or intraosseous phenytoin or
      fosphenytoin infusions. Phenytoin (20 mg/kg) was infused over 20 mins, and
      fosphenytoin (20 mg phenytoin equivalent kg) was infused over 7 mins. All
      infusions were followed by the administration of a 5-mL normal saline flush.
      MEASUREMENTS AND MAIN RESULTS: Blood samples (3 mL) were drawn for use in
      determining drug levels before infusions (baseline) and 0, 5, 10, 15, 20, 30, 40,
      50, 60, and 75 mins after the infusion had been completed. Repeated measures of
      analysis of variance were used to evaluate statistical significance (p <.05).
      Phenytoin levels were undetected at baseline. Free (10 to 20 &mgr;g/mL) and total
      (80 to 110 &mgr;g/mL) phenytoin levels were well above the therapeutic range
      (free, 1 to 2 &mgr;g/mL; total, 10 to 20 &mgr;g/mL) after infusion in the animals
      that received fosphenytoin. Significant differences in values were seen in free
      phenytoin levels at 0 to 10 mins (p <.05) and in total phenytoin levels at 0 to
      20 mins (p <.05) between intraosseous phenytoin or fosphenytoin administration.
      Similar differences were also seen when piglets that received intravenous
      phenytoin were compared with those that received intravenous fosphenytoin. From
      20 to 75 mins, all groups had free and total levels within the therapeutic range.
      There were no significant differences among heart rate and blood pressure in the
      groups. CONCLUSION: There is no need to adjust standard drug doses of phenytoin
      when given intraosseously. The initial high levels of phenytoin in the
      fosphenytoin groups are of concern because neurologic toxic effects may occur in
      humans at those levels. Slower infusion rates of fosphenytoin may be needed to
      avoid toxic levels.

PMID- 12813290
TI  - Administration of autologous fetal membranes: Effects on the coagulation in
      pregnant mini-pigs.
AB  - OBJECTIVE: A hallmark of the so-called amniotic fluid embolism is the induction
      of coagulation defects. Entry of meconium-free autologous amniotic fluid into the
      circulation, however, is innocuous. Little is known about the true causative
      agent or agents. The purpose of this study was to assess the effects of
      homogenized autologous fetal membranes (FM) on the coagulation system in the mini
      pig model. DESIGN: Laboratory study. SETTING: University institute animal
      laboratory. SUBJECTS: Six near-term pregnant, Gottingen-bred mini-pigs.
      INTERVENTIONS: After induction of general anesthesia, FM were col-lected from all
      animals by cesarean section. Animals received 2 g FM (shredded and suspended in
      lactated Ringer's solution) via an ear vein. MEASUREMENTS: Blood samples were
      taken from a central vein before administration (baseline), immediately after
      administration, every 10 mins until 90 mins after administration, and every 20
      mins until 150 mins after administration. The following parameters were measured:
      platelets, partial thromboplastin time, prothrombin time index, fibrinogen,
      factors II, V, VII, VIII, IX, X, XI, antithrombin III, and protein C. The values
      relative to baseline in the FM group were compared with a historical control
      group by rank order test. A p <.05 was considered significant. MAIN RESULTS: In
      the FM group (compared with the control group), platelets were lower; partial
      thromboplastin time was prolonged; fibrinogen was lower; prothrombin time index
      was lower (ie, prothrombin time was prolonged); protein C and antithrombin III
      were lower; and activity levels of factors V and VII were lower. The levels of
      factors II, VIII, IX, X, and XI showed a trend toward lower activity in the FM
      group, but the differences were not statistically significant. CONCLUSIONS: FM
      can activate coagulation in mini-pigs. The laboratory parameter changes seen are
      typical for disseminated intravascular coagulation. However, the full clinical
      picture of amniotic fluid embolism and disseminated intravascular coagulation
      could not be elicited despite the high dose of FM used.

PMID- 12813291
TI  - Surfactant and partial liquid ventilation via conventional and high-frequency
      techniques in an animal model of respiratory distress syndrome.
AB  - OBJECTIVE: To compare the physiologic and pathologic effects of conventional
      ventilation (CV) and high-frequency ventilation (HFV) during partial liquid
      ventilation (PLV) with perflubron after surfactant treatment with the results of
      HFV plus surfactant in an animal lung-injury model created by saline lavage. We
      also studied the dose effects of perflubron during HFV. DESIGN: Randomized
      experimental study. SETTING: Research animal laboratory. SUBJECTS: A total of 32
      newborn piglets. INTERVENTIONS: After lung injury was induced, the animals were
      randomized to one of four groups: a) CV + surfactant + perflubron to functional
      residual capacity (FRC); b) HFV + surfactant + perflubron to FRC; c) HFV +
      surfactant + 10 mL/kg perflubron; and d) HFV + surfactant. All then received
      intratracheal surfactant. After 30 mins, perflubron was administered to the PLV
      groups. The animals underwent ventilation for 20 hrs. MEASUREMENTS AND MAIN
      RESULTS: Arterial blood gases and hemodynamic variables were continuously
      monitored. Pulmonary histologic and morphometric analyses were performed after
      death or euthanasia at 20 hrs. All animals had sustained improvements in
      arterial/alveolar oxygen ratios, and no differences were observed among groups.
      All HFV groups required higher mean airway pressures to maintain oxygenation (p
      <.05). Hemodynamics did not differ among groups. Pathologic analysis demonstrated
      decreased lung injury in both cranial-dorsal (nondependent) and caudal-ventral
      (dependent) lobes of all animals treated with PLV when compared with those
      treated with HFV + surfactant (p <.05). CONCLUSIONS: After surfactant treatment,
      physiologic support over 20 hrs was similar during HFV with or without perflubron
      and CV with perflubron. All PLV modalities improved lung pathologic factors
      uniformly to a greater degree than did HFV + surfactant. A lower treatment volume
      of perflubron during HFV produced physiologic and pathologic results similar to
      those produced by perflubron with respect to FRC during either CV or HFV.

PMID- 12813292
TI  - Synchronized independent lung ventilation in palliated congenital heart disease
      with variable sources of pulmonary blood flow.
AB  - OBJECTIVE: Presentation of two patient studies demonstrating the use of
      synchronized independent lung ventilation in the management of acute respiratory
      failure in patients with complex palliated congenital heart disease and variable
      sources of pulmonary blood flow. DESIGN: Clinical course of two patients.
      SETTING: Cardiac intensive care unit in a tertiary care, university-affiliated
      pediatric teaching hospital. PATIENTS: Patient 1 was a 22-yr-old woman with a
      single ventricle and right lung blood flow supplied by a classic Glenn shunt and
      left lung blood flow through a systemic-to-pulmonary artery shunt. Patient 2 was
      a 12-yr-old boy with tetralogy of Fallot and complete common atrioventricular
      canal defect with right lung blood flow supplied by a classic Glenn shunt and
      left lung blood flow supplied by the right ventricle. Both patients presented
      with acute, left-sided lung disease and hypoxemia. INTERVENTIONS: We used
      selective bronchial intubation via a double-lumen tracheal tube with a bronchial
      extension for synchronized independent lung ventilation to permit high-pressure
      ventilation of the abnormal left lung low-pressure ventilation of the normal
      right lung supplied by a Glenn shunt. Inhaled nitric oxide was administered to
      both patients and continued in one when improved oxygenation was observed.
      MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gas measurements, mechanical
      indices of pulmonary function, and chest radiographs were closely followed.
      Synchronized independent lung ventilation contributed to improvements in systemic
      arterial blood oxygenation and alveolar ventilation allowing resumption of
      conventional ventilation in both patients. No adverse effects related to
      bronchial tube placement or maintenance occurred. CONCLUSION: Independent lung
      ventilation is an effective means of isolating the two lungs for differential
      ventilation, as well as the selective delivery of inhaled medications. In
      patients with unilateral lung disease and a Glenn shunt supplying the unaffected
      lung, selective lung ventilation allows aggressive treatment of the abnormal lung
      while optimizing flow through the Glenn shunt to maximize effective pulmonary
      blood flow, systemic oxygenation, and hemodynamics.

PMID- 12813293
TI  - Antithrombin concentrate with plasma exchange in purpura fulminans.
AB  - OBJECTIVE: To report successful treatment of three patients admitted with purpura
      fulminans. DESIGN: Three cases with purpura fulminans: clinical presentation,
      laboratory findings, treatment, and outcome. SETTING: A seven-bed medical and
      general surgical Intensive therapy unit in a district general hospital. PATIENTS:
      Three young patients with clinical and laboratory findings of severe
      meningococcal sepsis and purpura. INTERVENTIONS: Early replacement therapy with
      antithrombin concentrate after a single initial plasma exchange, together with
      conventional antibiotic and supportive treatment. MEASUREMENTS AND MAIN RESULTS:
      All three cases had abnormal coagulation profile consistent with disseminated
      intravascular coagulation, adult respiratory distress syndrome, impaired renal
      function, and severe hemodynamic instability requiring inotropic support. Plasma
      antithrombin levels were measured in all cases. All patients survived and made a
      good recovery. CONCLUSIONS: We consider that correction of antithrombin to
      supranormal levels may have a beneficial effect on survival and outcome in
      purpura fulminans despite sustained low levels of protein C.

PMID- 12813294
TI  - Ten days of orotracheal intubation with successful extubation in an infant with
      junctional epidermolysis bullosa.
AB  - OBJECTIVE: The most severe form of generalized junctional epidermolysis bullosa,
      the Herlitz variant, is associated with a number of extracutaneous
      manifestations. We report on a 45-day-old infant with laryngotracheobronchial
      mucosa involvement who underwent successful tracheal extubation after 10 days of
      orotracheal intubation and mechanical ventilatory support. Issues regarding
      airway management and mechanical ventilatory support in the pediatric intensive
      care unit are discussed.

PMID- 12813295
TI  - Heliox and high-frequency oscillatory ventilation: Has helium finally found its
      niche?

PMID- 12813296
TI  - Pediatric emergency department directors' benchmarking survey: fiscal year 2001.
AB  - OBJECTIVES: To answer basic questions, using precise definitions, regarding
      emergency department (ED) utilization, wait times, services, and attending
      physician staffing of representative pediatric EDs (PEDs). METHODS: Ten questions
      with precise definitions were developed and sent to members of the Ambulatory
      Pediatric Association's PED Directors' Special Interest Group in November of
      2001, with two repeated requests 3 and 6 months later. RESULTS: Twenty-one PEDs
      from 14 states, the District of Columbia, and Canada responded (41%). The average
      PED has 48,000 patient visits per year (range, 25,000-97,000). Two thirds have
      urgent care or fast track areas to see nonurgent patients, while only 29% have 23
      hour treatment units. The average admission rate is 13.2% (range, 6.8-20.8%). The
      average rate of patients who leave without being seen is 1.6%. The average
      patient waits 1 hour to see a physician and spends a total of 3 hours in the PED.
      The majority of attending staffing is by pediatric emergency medicine (PEM) Board
      certified/eligible physicians (73%), although a few PEDs are staffed only by PEM
      specialists. Attending staffing is 2.8 patients per attending per hour, or 0.36
      hours per patient, with more staffing for PEDs with higher admission rates or
      acuity. The average entry-level base salary for PED physicians in 2000 was
      117,250 dollars (range, 98,000 dollars-145,000 dollars). CONCLUSIONS:
      Benchmarking of PEM staffing and performance indicators by PEM directors yields
      important administrative data. PEDs have higher census and admission rates
      compared with information from all EDs, while their attending staffing, wait
      times, and rate of patients who leave without being seen are comparable to those
      of general EDs.

PMID- 12813297
TI  - Fractures in young children: are physicians in the emergency department and
      orthopedic clinics adequately screening for possible abuse?
AB  - OBJECTIVES: 1) To determine whether physicians are sufficiently investigating the
      cause of fractures in children younger than 3 years and 2) to find out what
      influences physicians' quality of history taking and documentation necessary to
      rule out inflicted trauma. DESIGN: Descriptive, retrospective chart review.
      SETTING: Pediatric emergency department and orthopedic clinic of an urban
      teaching hospital. SUBJECTS: Children younger than 3 years treated between
      January 1, 1995, and December 31, 1998, presenting with a fracture. RESULTS: A
      total of 653 charts met entry criteria. Information that was significantly
      lacking in the recorded history included witness presence, history of previous
      injury, review of past medical record, other injury description, and whether the
      injury was consistent with the development of the child. It was not possible to
      rule out inflicted injury in 42% of the patients. Four groups emerged from the
      entire cohort: group 1, accidental trauma, which made up 63% of the entire group
      (n = 413); group 2, inflicted trauma, which made up 13% (n = 85); group 3, missed
      inflicted trauma, which made up 23% (n = 151); and group 4, missed accidental
      trauma, which made up 0.6% (n = 4). Younger age of the child, multiple fractures,
      need for hospital admission, and the examining physician being a pediatrician
      positively influenced physicians' propensity to accurately report inflicted
      trauma. CONCLUSIONS: A large percentage of the charts reviewed contained
      inadequate documentation to explain the cause of fractures and thereby rule out
      inflicted trauma. Information in 23% of the charts reviewed aroused suspicion of
      inflicted trauma. There is a need to ensure that adequate information is obtained
      and documented in hospital records to rule out inflicted injury. This will
      require changes in the knowledge, skills, and attitudes of physicians. The use of
      forms, protocols, and periodic chart review will help to ensure compliance.

PMID- 12813298
TI  - Emergency medicine training programs' educational requirements in the management
      of psychiatric emergencies: current perspective.
AB  - OBJECTIVE: The purpose of this study was to determine the extent of training in
      clinical psychiatry that is provided and/or required by emergency medicine (EM)
      residency training programs and pediatric emergency medicine (PEM) subspecialty
      residency training programs. DESIGN/METHODS: A questionnaire was mailed to 114 EM
      residency directors and to all 50 PEM fellowship directors. Each director was
      asked to indicate the amount of psychiatric training that was required of
      residents or fellows in his or her program. Details concerning the exact
      structure of psychiatric training were solicited from those offering such
      training. RESULTS: There was a 76% response rate (n = 88) among EM programs, and
      76% (n = 59) of the respondents reported no formal training in the management of
      acute psychiatric emergencies. Only 14% (12 programs) provide a 1-month rotation
      in psychiatry. Of the 3-year programs, 14% (n = 11) offer 2-week psychiatric
      electives, and 9% (n = 8) offer some training. There was a 72% response rate
      among the PEM training programs. Only one of the 36 respondents provided a
      required 1-month rotation in psychiatry. Six programs stated the availability of
      a 1-month elective in psychiatry. Two programs reported 2 to 3 hours per year of
      core lecture time dedicated to psychiatric emergencies. CONCLUSIONS: Standardized
      psychiatric training is not required of most trainees in EM and PEM. Few (24%)
      training programs provide formal psychiatric training for their EM residents, and
      even fewer (< 3%) provide such training for their PEM fellows.

PMID- 12813299
TI  - Factors used by pediatric emergency medicine program directors to select their
      fellows.
AB  - BACKGROUND: Pediatric emergency medicine (PEM) recently has become a highly
      competitive subspecialty with twice the number of applicants for positions
      available. Little information exists on the characteristics that PEM programs
      desire in their applicants. We sought to assess the factors used by PEM program
      directors when ranking PEM fellow applicants in the National Resident Match
      Program (NRMP). METHODS: A 47-item questionnaire (adapted from a previously
      published questionnaire) was designed to assess the relative importance of
      various factors in the ranking of PEM fellow applicants in the NRMP. The
      questionnaire was mailed to all 43 PEM program directors that participated in the
      2001 NRMP. The program directors were asked to grade selection factors based on a
      five-point Likert scale: 1, unimportant; 2, somewhat important; 3, important; 4,
      very important; 5, critical. The factors addressed in the questionnaire included
      academic criteria, letters of recommendation, applicant characteristics, and
      aspects of the interview. In addition, we asked 10 yes-or-no questions pertaining
      to specific aspects of each program. Responses were tabulated and means and
      standard deviations reported. RESULTS: A program response rate of 93% (40/43) was
      obtained. The most important factors in granting an interview were
      recommendations from colleagues in PEM (4.21 +/- 0.78), research potential (3.81
      +/- 1.10), and reputation of the applicant's pediatric program (3.51 +/- 0.91).
      The least important factors in granting an interview were reputation of the
      applicant's undergraduate institution (1.76 +/- 0.86), medical school grades
      (1.83 +/- 0.87), and board scores (2.11 +/- 0.91). Letters from division chiefs
      of PEM (4.15 +/- 0.78) and clinical faculty in PEM (4.06 +/- 0.82) were
      considered the most important letters of recommendation, whereas letters from
      basic science faculty were considered the least important (1.89 +/- 0.96).
      Ability to work with a team (4.66 +/- 0.42), compatibility with the program (4.65
      +/- 0.35), commitment to hard work (4.55 +/- 0.45), ability to grow in knowledge
      (4.41 +/- 0.58), ability to solve problems (4.36 +/- 0.63), ability to listen
      (4.34 +/- 0.65), and ability to articulate thoughts (4.32 +/- 0.59) were the most
      important characteristics in the final ranking of candidates. Thirty percent
      (12/40) of the program directors stated that it was important for the program to
      "match" its top choice. The majority of programs have a selection committee that
      contributes to the final ranking of applicants. CONCLUSIONS: The results of this
      study suggest that a rather subjective but uniform prioritization of criteria is
      used in evaluating PEM program applicants. Awareness of these factors would
      enable applicants to make a critical self-analysis of their strengths and
      weaknesses prior to the submission of their applications.

PMID- 12813300
TI  - Validation of a decision rule identifying febrile young girls at high risk for
      urinary tract infection.
AB  - OBJECTIVE: To validate a previously published clinical decision rule to predict
      risk of urinary tract infection in febrile young girls. METHODS: We performed a
      retrospective case-control study at a children's hospital emergency department in
      a different city than that in which the original derivation study took place.
      Girls younger than 2 years in whom urinalysis and urine culture were performed
      for evaluation of fever were eligible. Cases consisted of all patients with a
      positive urine culture result, defined as 50,000 or more colony-forming units per
      milliliter of a urinary tract pathogen (n = 98). A random sample of patients with
      a negative urine culture result (n = 114) was also selected as controls. The
      clinical prediction rule included five risk factors: age younger than 12 months,
      white race, temperature of 39.0 degrees C or higher, absence of any other
      potential source of fever, and fever for 2 days or more. The sensitivity and
      false-positive rate of this rule were calculated at different cutoff values.
      RESULTS: The overall discriminative ability of the rule, as indicated by the area
      under the receiver-operator characteristic curve (AUC), was similar in this
      validation sample (AUC = 0.72) to that in the original study (AUC = 0.76).
      However, in the validation sample, the presence of three or more risk factors
      (rather than two or more as in the original study) appeared to be the optimum
      cutoff to define a positive rule, which results in an indication for obtaining
      further diagnostic testing (sensitivity, 88% [95% CI, 79-94%]; false-positive
      rate, 70% [95% CI, 61-79%]). CONCLUSION: A simple clinical decision rule
      previously developed to predict urinary tract infection based on five risk
      factors performs similarly in a different patient population.

PMID- 12813301
TI  - Neonatal mastitis.

PMID- 12813302
TI  - Traumatic asphyxia in a 6-year-old boy.

PMID- 12813303
TI  - Ingestion of tea tree oil (Melaleuca oil) by a 4-year-old boy.
AB  - A 4-year-old boy ingested a small quantity of tea tree oil. Within 30 minutes, he
      became ataxic and shortly thereafter progressed to unresponsiveness; he was
      endotracheally intubated by paramedics. His neurologic status improved gradually
      over 10 hours, and he remains well on follow-up. Tea tree oil is an increasingly
      popular topical antiseptic that is available in a wide variety of products, often
      without warning labels. Healthcare providers should be aware of the common uses
      of tea tree oil, as well as its potential toxicity.

PMID- 12813304
TI  - Mastocytosis: the pediatric emergency physician's perspective.

PMID- 12813305
TI  - Pheochromocytoma unmasked by imipramine in an 8-year-old girl.

PMID- 12813306
TI  - Potential applications of proton nuclear magnetic resonance spectroscopy in the
      diagnosis and management of methanol intoxication in the pediatric population.

PMID- 12813307
TI  - International pediatric emergency care: establishment of a new specialty in a
      developing country.
AB  - BACKGROUND: Emergency medicine is being established as a unique and independent
      specialty throughout the world. Pediatric emergency medicine, however, is a
      relatively new subspecialty in the United States and a newer subspecialty in the
      rest of the world. In most of Europe and Asia, this specialty has yet to be
      developed. OBJECTIVE: To analyze the establishment of a new pediatric emergency
      care system in a developing country and identify areas of need and potential
      collaboration. SETTING: Pristina University Hospital, the main academic medical
      center in Kosovo, Federal Republic of Yugoslavia. METHODS: Data were collected
      using convenience sample surveys of all emergency visits in 2001, hospital
      admissions, health department statistics, and interviews with government
      officials and healthcare providers. RESULTS: Emergency care of children in Kosovo
      is provided by three parallel 24-hour clinic systems. During 2001, approximately
      31,000 children sought emergency care (10,000 in the pediatric clinic, 5000 in an
      emergency facility, and 16,000 in the infectious disease clinic). There was no
      coordination or cooperation between these different facilities. No attempt was
      made to diagnose acute otitis media or urinary tract infection in young children.
      No records were kept. No physician in this study had pediatric emergency medicine
      and/or emergency medicine training. Prehospital providers had limited equipment
      and training. CONCLUSIONS: Hospital clinic systems in this environment provide
      high-volume and often a high level of acute care. Barriers to improved care
      include limited specialized training, lack of coordination between departments,
      and failure to establish a medical records system.

PMID- 12813308
TI  - The Pediatric Emergency Care Applied Research Network (PECARN): rationale,
      development, and first steps.
AB  - Since its formal recognition as a medical specialty, the field of pediatric
      emergency medicine has made substantial advances with respect to its scope and
      sophistication. These advances have occurred in clinical practice as well as in
      the research base to improve clinical practice. There remain, however, many areas
      in emergency medical services for children (EMSC) in the out-of-hospital,
      emergency department (ED), and hospital settings that suffer from a lack of data
      to guide practice. In an effort to expand the quality and quantity of research in
      pediatric emergency care, the Pediatric Emergency Care Applied Research Network
      (PECARN) was created in October of 2001. PECARN is the first federally funded
      national network for research in EMSC and is the result of cooperative agreement
      grants funded through the Health Resources and Services Administration with the
      purpose of developing an infrastructure capable of overcoming inherent barriers
      to EMSC research. Among these recognized barriers are low incidence rates of
      serious pediatric emergency events, the need for large numbers of children from
      varied backgrounds to achieve broadly representative study samples, lack of an
      infrastructure to test the efficacy of pediatric emergency care, and the need for
      a mechanism to translate study results into clinical practice. PECARN will serve
      as a national platform for collaborative research involving the continuum of care
      within the EMSC system, including out-of-hospital care, patient transport, ED and
      in-hospital care, and rehabilitation. This article describes the history of EMSC,
      the need for a national collaborative research network in EMSC, the organization
      and development of PECARN, and the work plan for the network.

PMID- 12813309
TI  - Pediatric emergency medicine: legal briefs.

PMID- 12813310
TI  - Medical director dilemmas.

PMID- 12813311
TI  - Transfer for "pneumonia".

PMID- 12813312
TI  - Toxic seizures in children: case scenarios and treatment strategies.

PMID- 12813313
TI  - Transporting the family by air.

PMID- 12813314
TI  - Near-fatal strangulation injury caused by a turnstile: another incident.

PMID- 12813315
TI  - Serum tumor necrosis factor-alpha and interleukin-6 levels in neonatal sepsis.

PMID- 12813317
TI  - Variability without value?

PMID- 12813318
TI  - Role of gene polymorphisms in sepsis.

PMID- 12813320
TI  - Experienced nurses + autonomy = better patient outcomes.

PMID- 12813319
TI  - Out of the frying pan and into the fire: neurodevelopmental outcome in pediatric
      intensive care unit survivors of serious brain injury.

PMID- 12813321
TI  - Impact of American College of Surgeons verification on trauma outcomes.
AB  - OBJECTIVE: The purpose of this study was to compare the impact of trauma patient
      outcomes before and after Level II American College of Surgeons (ACS)
      verification was received in a not-for-profit community hospital. METHODS: This
      was a retrospective analysis of hospital discharge data for timeframes before and
      after Level II ACS verification was conducted. Originally, 8,674 patients were
      identified using the International Classification of Diseases, 9th Revision codes
      for trauma. These data were parsed to 7,811 patients by using International
      Classification of Diseases, 9th Revision codes 800 xx through 959.9 x, which
      signify an admitting diagnosis of trauma; 3,835 of the patients were admitted
      after the July 28, 1998, verification date. Blunt injuries constituted the vast
      majority of the patients (n = 7,488). Outcome measures studied included changes
      in length of stay (LOS), mortality, and total cost. Internal control was coronary
      artery bypass graft patients at the same hospital, and external control was
      trauma patients at a non-ACS hospital over the same time period. Data are
      presented with p values and SE and the ratio of observed/expected values on the
      basis of the all-payer severity-adjusted diagnosis-related group severity model.
      RESULTS: The two timeframes exhibited statistically different outcomes in several
      variables. Adjusting for severity postverification, LOS was 10% less (p < 0.000).
      Similarly, severity-adjusted mortality observed/expected ratios were
      significantly different: 0.81 before versus 0.59 after (p < 0.000). The severity
      adjusted ratio of costs found that the postverification era was 5% lower (p <
      0.000). The contribution margin of the trauma patient population to the hospital
      well exceeded any postverification costs. Both control groups exhibited no
      significant changes in their severity-adjusted outcomes, which could have
      invalidated these results. CONCLUSION: This study suggests that the efforts and
      resources consumed achieving ACS Level II trauma center verification appear to
      result in desired outcomes as evidenced by decreased LOS, reduced in-hospital
      mortality rates, reduced cost, and improved contribution margins.

PMID- 12813322
TI  - Emergency ventilatory management in hemorrhagic states: elemental or detrimental?
AB  - BACKGROUND: A study was performed to demonstrate that slower respiratory rates
      (RRs) of positive-pressure ventilation can preserve adequate oxygenation and acid
      base status in hemorrhagic states, whereas "normal" or higher RRs worsen
      hemodynamics. METHODS: Eight swine (ventilated with 12 mL/kg tidal volume, 0.28
      Fio(2); RR of 12 breaths/min) were hemorrhaged to < 65 mm Hg systolic arterial
      blood pressure (SABP). RRs were then sequentially changed every 10 minutes to 6,
      20, 30, and 6 breaths/min. RESULTS: With RRs at 6 breaths/min, the animals
      maintained pH > 7.25/Sao(2) > 99%, but increased mean SABP (from 65 to 84 mm Hg;
      p < 0.05), time-averaged coronary perfusion pressure (CPP) (from 50 +/- 2 to 60
      +/- 4 mm Hg; p < 0.05), and cardiac output (Qt) (from 2.4 to 2.8 L/min; p <
      0.05). With RRs of 20 and 30 breaths/min, SABP (73 and 66 mm Hg), CPP (47 +/- 3
      and 42 +/- 4 mm Hg), and Qt (2.5 and 2.4 L/min) decreased, as did Pao(2) and
      Paco(2) (< 30 mm Hg), with p < 0.05 for each comparison, respectively. When RR
      returned to 6 breaths/min, SABP (95 mm Hg), CPP (71 +/- 6 mm Hg), and Qt (3.0
      L/min) improved significantly (p < 0.05). CONCLUSION: After even moderate levels
      of hemorrhage in animals, positive-pressure ventilation with "normal" or higher
      RRs can impair hemodynamics. Hemodynamics can be improved with lower RRs while
      still maintaining adequate oxygenation and ventilation.

PMID- 12813323
TI  - Rib fracture pain and disability: can we do better?
AB  - OBJECTIVE: The purpose of this study was to determine the magnitude and duration
      of pain and disability in patients with rib fractures treated using current
      standard therapy. This was a prospective case series. METHODS: Injured patients
      with a chest radiographic diagnosis of one or more rib fractures between June 1,
      2001, and October 31, 2001, were asked to participate. Pain levels were assessed
      at days 1, 5, 30, and 120 after injury using a visual pain scale (0-10).
      Disability at 30 days was assessed using the SF-36 Health Status Survey, and the
      total number of days lost from work/usual activity was recorded at day 120. The
      setting was a university-based Level I trauma center. RESULTS: Forty patients
      with a mean of 2.7 +/- 1.6 rib fractures were enrolled. Twenty-three patients had
      isolated rib fractures and 17 patients had associated extrathoracic injuries.
      Mean rib fracture pain was 3.5 +/- 2.1 at 30 days and 1.0 +/- 1.4 at 120 days.
      For patients with associated extrathoracic injuries, rib pain was equivalent to
      pain in the rest of the body at all intervals. When compared with the chronically
      ill reference population of the RAND Medical Outcomes Study, our patients as a
      group were more disabled at 30 days (p < 0.001) in all categories except
      emotional stability, where they showed equivalent disability, and in their
      perception of general health, where they were significantly less disabled (p <
      0.001). The total mean days lost from work/usual activity was 70 +/- 41. Patients
      with isolated rib fractures went back to work/usual activity at a mean of 51 +/-
      39 days compared with 91 +/- 33 days in patients with associated extrathoracic
      injuries (p < 0.01). CONCLUSION: Rib fractures are a significant cause of pain
      and disability in patients with isolated thoracic injury and in patients with
      associated extrathoracic injuries. Developing new therapies to accelerate pain
      relief and healing would substantially improve the outcome of patients with rib
      fractures.

PMID- 12813324
TI  - Human polymorphonuclear cell death after exposure to resuscitation fluids in
      vitro: apoptosis versus necrosis.
AB  - BACKGROUND: Resuscitation fluids can have variable effects on key functions of
      circulating polymorphonuclear neutrophils (PMNs) such as oxidative burst,
      chemotaxis, and bacterial killing. We hypothesized that choice of resuscitation
      fluids will also affect the rate of PMN apoptosis. To test this, we studied
      cellular death (apoptosis and necrosis) in human PMNs after brief exposure to
      different hypertonic and isotonic fluids. METHODS: Blood from 12 volunteers was
      incubated for 1 hour at 37 degrees C in normal saline, 6.0% dextran-70, 7.5%
      hypertonic saline, and 7.5% hypertonic saline with 6% dextran-70. Isolated PMNs
      were double labeled with fluorescein-Annexin V and propidium iodide, and
      apoptosis and necrosis were measured using flow cytometry. Caspase activation was
      also detected with flow cytometry using pan-caspase inhibitor (carbobenzoxy-valyl
      alanyl-aspartyl-fluoromethylketone) in non-isolated whole blood samples to
      determine apoptosis. Finally, cDNA macroarrays were used to evaluate the
      expression of 23 genes involved in the regulation of cell cycling and apoptosis.
      RESULTS: Exposure to hypertonic fluids (hypertonic saline and 7.5% hypertonic
      saline with 6% dextran-70) significantly (p < 0.05) increased necrosis in
      isolated PMNs. In whole blood samples, PMNs exposed to dextran demonstrated
      significant apoptosis as evidenced by increased caspase activation. Dextran was
      the only fluid that affected leukocyte gene expression, inducing significant up
      regulation of Rb gene transcription. CONCLUSION: Hypertonic fluids and dextran
      decrease human polymorphonuclear cell survival through necrotic and apoptotic
      pathways, respectively.

PMID- 12813325
TI  - Comparative analysis of hemostatic agents in a swine model of lethal groin
      injury.
AB  - BACKGROUND: Techniques for better hemorrhage control after injury could change
      outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to
      test whether the use of various hemostatic agents would decrease bleeding and
      improve early survival. METHODS: A complex groin injury was created in 30
      Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury
      included semitransection of the proximal thigh and complete division of the
      femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6
      animals per group) no dressing (ND), standard dressing (SD), SD and Rapid
      Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD
      and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes)
      resuscitation was started 30 minutes after injury. We measured blood loss, early
      mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g.,
      cardiac output, blood pressure, hemoglobin, metabolic acidosis). RESULTS:
      Application of wound dressing decreased mortality in all groups compared with the
      ND group (83% mortality). However, this difference was significant (p < 0.05)
      only for the QuikClot hemostatic agent (0% mortality). Before the application of
      dressing (first 5 minutes), there were no differences in blood loss between the
      groups. After application of dressings, the QC group had the lowest blood loss
      (4.4 +/- 1.4 mL/kg). CONCLUSION: Of the hemostatic agents tested, QuikClot
      improved survival and decreased bleeding in a swine model of lethal vascular and
      soft tissue injury.

PMID- 12813326
TI  - Immediate closure of the open abdomen with bilateral bipedicle anterior abdominal
      skin flaps and subsequent retrorectus prosthetic mesh repair of the late giant
      ventral hernias.
AB  - BACKGROUND: Management of the open abdomen in trauma and nontrauma patients is
      difficult, and some areas of controversy remain. Gastrointestinal fistulas are
      serious complications that are associated with significant mortality. We present
      our method for management of patients with open abdomen and also present a
      logical technique of subsequent repair of the late giant ventral hernias that
      uniformly occur in these patients. METHODS: From January 1992 to December 2001,
      nine patients with open abdomen underwent successful immediate closure with
      bilateral bipedicle anterior abdominal skin flaps. The major points of this
      technique of abdominal closure are coverage of abdominal viscera with absorbable
      mesh and mobilization of the skin and subcutaneous tissue on both sides of the
      abdominal wound to cover the absorbable mesh. All patients had uneventful
      recovery and also had subsequent late giant ventral hernias. Repair of the late
      giant ventral hernias was performed several months later by inserting a large
      sheet of nonabsorbable mesh under the rectus abdominis muscles that form the neck
      of the ventral hernia bilaterally. This technique of ventral hernia repair is
      also called retrorectus prosthetic mesh repair. RESULTS: Five men and four women
      were entered into the study. The age ranged from 22 to 53 years (median, 35
      years). Seven patients suffered from blunt and penetrating trauma and two
      patients suffered from nontrauma causes. All patients with immediate closure of
      the open abdomen had uneventful recovery. Late giant ventral hernias (diameter, >
      10 cm) occurred in all patients. The time from closure of the open abdomen to
      subsequent repair of the giant ventral hernias ranged from 7 to 48 months
      (median, 14 months). Follow-up after hernia repair ranged from 1 to 72 months
      (median, 9 months), and we have seen no evidence of recurrence. CONCLUSION:
      Immediate closure of the open abdomen with bilateral bipedicle anterior abdominal
      skin flaps is an effective technique for dealing with such potentially
      complicated problems. Management of late giant ventral hernias with retrorectus
      prosthetic mesh repair is theoretically reasonable and, so far, no recurrence has
      been observed in our patients.

PMID- 12813327
TI  - The cushion effect.
AB  - BACKGROUND: The pattern and severity of crash injury depends on a complex
      interaction of biomechanical factors such as deceleration velocity at impact
      (delta-V), seat-belt and airbag use, and type of impact. Human body
      characteristics such as height and weight may play an important role. We
      hypothesized that body mass index (BMI) will influence crash injury patterns.
      METHODS: The University of Michigan Program for Injury Research and Education
      database was queried. Three cohorts were analyzed, lean (BMI </= 25 kg/m2),
      overweight (BMI 25-30 kg/m2), and obese (BMI > 30 kg/m2) RESULTS: There were 189
      detailed crash cases, with 22 fatalities. There was an increased risk of fatal
      outcome associated with the obese cohort (adjusted odds ratio, 4.2 compared with
      lean; p = 0.04). Age, delta-V, seat-belt use, and type of impact were independent
      predictors of Injury Severity Score (ISS). After adjusting for other modifiers,
      being overweight was associated with decreased ISS (p = 0.03) and abdominal
      maximal Abbreviated Injury Scale (mAIS) score (p = 0.008) when compared with the
      lean cohort. However, the lower extremity mAIS score increased when overweight (p
      = 0.03) and obese cohorts (p = 0.001) were compared with the lean cohort.
      CONCLUSION: Although no difference in ISS was identified between the lean and
      obese cohorts, there was an increase in mortality with the obese cohort. The
      severity of lower extremity injuries increased with increasing BMI. The
      overweight cohort was associated with lower ISS and abdominal mAIS score compared
      with the lean cohort. This protection may be attributable to an increase in
      insulating tissue, or a "cushion effect," without a significant increase in mass
      and momentum.

PMID- 12813328
TI  - Patterns of injury to restrained children in side impact motor vehicle crashes:
      the side impact syndrome.
AB  - BACKGROUND: Injury patterns among children in frontal collisions have been well
      documented, but little information exists regarding injuries to children in side
      impact collisions. METHODS: Restrained children 14-years-old or younger admitted
      to the hospital for crash injuries were analyzed. Data concerning injuries,
      medical treatment, and outcome were correlated with crash data. Case reviews
      achieved consensus regarding injury contact points. Side impacts were compared
      with frontal impacts. These results were then compared with data from the
      National Automotive Sampling System. RESULTS: There were no differences between
      the groups with respect to age, sex, restraint type, or seat position. Compared
      with frontal crashes, children in side impacts were more likely to have an Injury
      Severity Score > 15 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.8)
      and were more likely to have Abbreviated Injury Scale score 2+ injuries to the
      head (OR, 2.5; 95% CI, 1.4-4.4), chest (OR, 4.0; 95% CI, 2.0-8.0), and cervical
      spine (OR, 3.7; 95% CI, 1.2-11.3). When compared with National Automotive
      Sampling System data, similar trends were seen regarding Abbreviated Injury Scale
      score 2+ injuries to the head, chest, and extremities. CONCLUSION: In this study
      population, side impacts resulted in more injuries to the head, cervical spine,
      and chest. Knowledge of this pattern-the side impact syndrome-can help guide
      diagnosis, treatment, and prevention strategy.

PMID- 12813329
TI  - An analysis of pediatric gunshot wounds treated at a Level I pediatric trauma
      center.
AB  - BACKGROUND: We reviewed the incidence and injury severity of children with
      gunshot wounds (GSWs) at our hospital. METHODS: We compared trauma registry,
      emergency unit (EU), and admissions data from January 1993 to June 1996 (period
      I) and July 1996 to December 1999 (period II). Outcome measures included EU
      disposition (death, immediate operation, pediatric intensive care unit, ward),
      injury severity, mortality, and injury cause (accidental, intentional). RESULTS:
      We treated 437 children for GSWs in the EU, with 238 (54%) admissions and 199
      discharges. Comparing period I versus period II, patients treated declined from
      288 to 149 (-52%, p < 0.001), and admissions decreased from 159 to 79 (-50%, p <
      0.001). Injury severity increased from 35% to 57% (p < 0.001). Patients requiring
      immediate operations increased from 20% to 42% (p < 0.001). Direct ward
      admissions declined from 65% to 43% (p < 0.001). Deaths occurred in 3% of
      patients in both time periods. Accidental and intentional GSWs were evenly
      divided. CONCLUSION: An alarming number of children, an average of 62 children
      annually, were treated for GSWs at our hospital. Despite a 52% reduction in GSWs,
      the percentage of severely injured patients increased by 63%. These data
      emphasize the importance of prevention, education, early assessment, and
      operative treatment.

PMID- 12813330
TI  - The positive predictive value of rib fractures as an indicator of nonaccidental
      trauma in children.
AB  - BACKGROUND: Rib fractures have a strong association with nonaccidental trauma
      (NAT) and severe trauma. The purposes of this study were to evaluate rib
      fractures in children to determine (1) the positive predictive value of a rib
      fracture in defining NAT and (2) the frequency of rib fractures as the only
      skeletal manifestation of NAT. METHODS: We reviewed the medical records and
      imaging of all children with rib fractures over a 6-year period. NAT was
      determined by the Child Advocacy and Protection team. RESULTS: In children
      younger than 3 years of age, the positive predictive value (PPV) of a rib
      fracture as an indicator of NAT was 95%. The positive predictive value increased
      to 100% once historical and clinical circumstance excluded all other causes for
      rib fractures. CONCLUSION: In this study, rib fracture(s) were the only skeletal
      manifestation of NAT in 29% of the children.

PMID- 12813331
TI  - Prevention of venous thromboembolism in the rehabilitation phase after spinal
      cord injury: prophylaxis with low-dose heparin or enoxaparin.
AB  - BACKGROUND: This prospective, multicenter study compared low-dose unfractionated
      heparin (UFH) with enoxaparin for prophylaxis against venous thromboembolism
      (VTE) during the rehabilitation phase after spinal cord injury. METHODS: After 2
      weeks of acute-phase prophylaxis, patients without objective evidence of VTE
      entered the rehabilitation phase and received up to 6 additional weeks of
      thromboprophylaxis with either UFH 5,000 U every 8 hours or enoxaparin 40 mg once
      daily. Patients then underwent repeat bilateral lower extremity duplex
      ultrasonography. RESULTS: Among 119 patients who completed the rehabilitation
      phase and had adequate imaging, new VTE was demonstrated in 13 of 60 UFH versus 5
      of 59 enoxaparin patients (21.7% vs. 8.5%; p = 0.052). Only one patient from each
      group was discontinued from the study because of bleeding. CONCLUSION: In this
      nonrandomized comparison, enoxaparin appeared more effective than heparin in the
      prevention of thromboembolic complications during rehabilitation after spinal
      cord injury. Both interventions were safe in this population.

PMID- 12813332
TI  - Prevention of venous thromboembolism in the acute treatment phase after spinal
      cord injury: a randomized, multicenter trial comparing low-dose heparin plus
      intermittent pneumatic compression with enoxaparin.
AB  - BACKGROUND: The risk of venous thromboembolism is high after spinal cord injury
      (SCI). This prospective, multicenter study compared unfractionated heparin (UFH)
      plus intermittent pneumatic compression (IPC) to enoxaparin alone as
      thromboprophylaxis after SCI. METHODS: Patients with acute SCI were randomly
      assigned to receive either UFH, 5,000 U every 8 hours, in combination with IPC or
      enoxaparin, 30 mg every 12 hours. Outcome measures were deep vein thrombosis,
      pulmonary embolism, and major bleeding after 2 weeks of prophylaxis. RESULTS:
      Among 107 assessable patients, the incidence of venous thromboembolism was 63.3%
      with UFH-IPC versus 65.5% with enoxaparin (p = 0.81). The incidence of PE was
      18.4% with UFH-IPC versus 5.2% with enoxaparin (p = 0.03). Among all randomized
      patients, the incidence of major bleeding was 5.3% with UFH-IPC versus 2.6% with
      enoxaparin (p = 0.14). CONCLUSION: In the acute treatment phase after SCI, safety
      and thromboprophylactic efficacy were generally similar with UFH-IPC and
      enoxaparin.

PMID- 12813333
TI  - Acute traumatic coagulopathy.
AB  - BACKGROUND: Traumatic coagulopathy is thought to be caused primarily by fluid
      administration and hypothermia. METHODS: A retrospective study was performed to
      determine whether coagulopathy resulting from the injury itself is a clinically
      important entity in severely injured patients. RESULTS: One thousand eight
      hundred sixty-seven consecutive trauma patients were reviewed, of whom 1,088 had
      full data sets. Median Injury Severity Score was 20, and 57.7% had an Injury
      Severity Score > 15; 24.4% of patients had a significant coagulopathy. Patients
      with an acute coagulopathy had significantly higher mortality (46.0% vs. 10.9%;
      chi2, p < 0.001). The incidence of coagulopathy increased with severity of
      injury, but was not related to the volume of intravenous fluid administered (r2 =
      0.25, p < 0.001). CONCLUSION: There is a common and clinically important acute
      traumatic coagulopathy that is not related to fluid administration. This is a
      marker of injury severity and is related to mortality. A coagulation screen is an
      important early test in severely injured patients.

PMID- 12813334
TI  - Liver cirrhosis: an unfavorable factor for nonoperative management of blunt
      splenic injury.
AB  - BACKGROUND: Nonoperative management (NOM) of blunt splenic injury (BSI) is
      currently a well-accepted treatment modality for hemodynamically stable patients.
      More than 60% of BSI patients can be successfully treated without operation. Old
      age, high-grade injury, contrast blush, and multiple associated injuries were
      reported to have a higher failure rate but not to be exclusive of NOM. The
      purpose of this study was to review the treatment courses and results of a
      special group of BSI patients with coexistent liver cirrhosis. Factors leading to
      poor results were analyzed and treatment strategy was proposed accordingly.
      METHODS: During a 5-year period, 487 patients with BSI were treated following a
      standard protocol. Twelve of them had underlying liver cirrhosis. The medical
      records, radiographic findings, laboratory data, and operative variables were
      retrospectively reviewed. RESULTS: Eighty-nine (18%) patients had immediate
      celiotomy for splenic hemorrhage with unstable hemodynamic status, 59 (12%) had
      non-spleen-related or nontherapeutic laparotomy, and 339 (70%) patients received
      NOM initially. Failure of NOM was found in 74 patients (22%). Twelve patients
      with initial NOM had coexistent liver cirrhosis. The amount of blood transfusion
      within 72 hours after admission for these 12 patients ranged from 4 to 26 units.
      Patients with coexistent liver cirrhosis and BSI had a significantly higher NOM
      failure rate (92% vs. 19%). In NOM failure patients, those with liver cirrhosis
      had lower Injury Severity Scores, lower splenic injury severity grades, more
      blood transfusions, and a higher mortality rate. Risk factors for mortality in
      these patients included a higher Injury Severity Score, a severely elevated
      prothrombin time (PT), a larger transfusion requirement, and a lower serum
      albumin level. CONCLUSION: Liver cirrhosis with subsequent development of portal
      hypertension, splenomegaly, and coagulopathy makes spontaneous hemostasis of the
      injured spleen difficult. NOM for BSI patients with coexistent liver cirrhosis
      carries a high failure and mortality rate. NOM may be successful in only a small
      group of patients with low-grade single-organ injury and with a normal or mildly
      elevated PT. Aggressive correction of coagulopathy should be performed in these
      patients. High-grade splenic injury, multiple associated injuries, and an
      elevated PT are indicators for early surgery. The mortality rate is high in
      patients with a severely prolonged PT irrespective of treatment modalities.

PMID- 12813335
TI  - Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary
      inflammatory response caused by hemorrhagic shock.
AB  - BACKGROUND: The treatment of hemorrhagic shock (HeS) with large volumes of fluid
      does not ensure an adequate peripheral perfusion or prevent inflammatory
      activation despite hemodynamic recovery. The purpose of this study was to compare
      the effect of hypertonic saline (HTS) and isotonic saline (IS) solutions on
      oxygenation, perfusion, tumor necrosis factor-alpha and interleukin-6 levels,
      accumulation of polymorphonuclear neutrophils, and pulmonary perivascular edema
      in the treatment of controlled HeS in rats. METHODS: Wistar rats submitted to HeS
      for 50 minutes (mean arterial pressure, 45-50 mm Hg) were treated with IS at
      three times the bled volume or with 5 mL/kg HTS. RESULTS: The animals treated
      with HTS presented higher oxygenation and perfusion indices (p < 0.0001); lower
      arterial lactate, tumor necrosis factor-alpha, and interleukin-6 levels (p <
      0.0001); less pulmonary perivascular edema and polymorphonuclear neutrophil
      sequestration (p < 0.0001); and lower mortality (p < 0.01) than those that
      received IS. CONCLUSION: HTS improved tissue oxygenation and perfusion and
      reduced systemic and pulmonary inflammatory responses compared with IS in the
      treatment of HeS in rats.

PMID- 12813336
TI  - Pelvic fractures in pediatric and adult trauma patients: are they different
      injuries?
AB  - BACKGROUND: Many aspects of pediatric trauma are considerably different from
      adult trauma. Very few studies have performed comprehensive comparisons between
      pediatric and adult pelvic fractures. The purpose of this study was to compare
      the incidence of pelvic fracture, the epidemiologic characteristics, type of
      associated abdominal injuries, and outcomes between pediatric (age </= 16 years)
      and adult (age > 16 years) patients. METHODS: This was a trauma registry study
      that included all blunt trauma admissions at a Level I trauma center during an 8
      year period. The incidence and severity of pelvic fractures, associated abdominal
      injuries, need for blood transfusion, and mortality in the two age groups were
      compared with the two-sided Fisher's exact test. Stepwise logistic regression
      analysis was used to identify independent risk factors for associated abdominal
      injuries in pelvic fractures in the two age groups. RESULTS: The incidence of
      pelvic fractures was 10.0% (1,450 of 14,568) in the adult group and 4.6% (95 of
      2,062) in the pediatric group (p < 0.0001). In motor vehicle and pedestrian
      injuries, adults were twice as likely and in falls from heights > 15 ft seven
      times as likely as children to suffer pelvic fractures. However, age group was
      not a significant predictor of the severity of pelvic fracture. Only 9.5% of
      pediatric fractures and 8.8% of adult fractures had a pelvis Abbreviated Injury
      Scale (AIS) score >/= 4. The incidence of associated abdominal injuries was high
      but similar in the two age groups (16.7% in adults and 13.7% in children, p =
      0.48). Motor vehicle crash, pelvis AIS score >/= 4, and fall from height > 15 ft
      were significant predictors of associated abdominal injuries in the adult but not
      the pediatric group. The incidence of associated gastrointestinal injuries was
      similar in the two age groups (5.3% in children and 3.3% in adults, p = 0.37).
      The incidence of solid organ injuries was nearly identical in both groups (11.6%
      in children and 11.5% in adults). The need for blood transfusions and
      angiographic intervention was not significantly different between the two age
      groups. Exsanguination because of bleeding related to the pelvic fracture was
      responsible or possibly responsible in 42 deaths (2.9%) in the adult group and no
      deaths in the pediatric group. CONCLUSION: Pediatric trauma patients are
      significantly less likely than adults to suffer pelvic fractures, although the
      age group is not a significant risk factor for the severity of pelvic fracture.
      The incidence of associated abdominal injuries is high and similar in the two age
      groups. Motor vehicle crash, fall from a height, and pelvis AIS score >/= 4 were
      significant predictors of associated abdominal injuries in the adult but not the
      pediatric patients. The need for blood transfusion is similar in both groups
      irrespective of Injury Severity Score and pelvis AIS score. The mortality
      resulting from exsanguination related to pelvic fractures is very low, especially
      in pediatric patients.

PMID- 12813337
TI  - Expandable nail system for osteoporotic humeral shaft fractures: preliminary
      results.
AB  - BACKGROUND: Conventional nails rely on interlocking screws for axial and
      rotational stability. Such screws have poor fixation in patients with poor bone
      quality (osteopenia). The Fixion nail does not depend on interlocking screws
      axial and rotational stability is instead achieved by nail expansion. Therefore,
      this nail may be better suited for patients with poor bone quality who require
      humeral stabilization. METHODS: The system was used to manage 25 unstable humerus
      shaft fractures in osteoporotic bone. An antegrade approach was used in 18
      patients and a retrograde approach was used in 7 patients. RESULTS: There were no
      intra- or postoperative complications. Postoperatively, all fractures were stable
      and had healed by week 16. The mean operative time was 35 +/- 10 minutes (+/- SD)
      including 1.5 +/- 0.5 minutes of fluoroscopy time. CONCLUSION: The results of
      this study show that use of this nailing system is associated with minimal
      complications, predictable fracture healing, and excellent functional outcomes in
      a cohort of elderly patients with poor bone quality and humeral shaft fractures
      requiring stabilization. Further confirmation by larger prospective trials is
      necessary.

PMID- 12813338
TI  - Tibial lengthening: technique for speedy lengthening by external fixation and
      secondary internal fixation.
AB  - BACKGROUND: The conventional Ilizarov technique for tibial lengthening is
      frequently time-consuming, causes suffering, and is associated with many
      complications. This study takes a retrospective approach to investigate the
      outcome of applying a slightly speedier procedure using an Ilizarov apparatus and
      secondary internal fixation. METHODS: Twelve adult patients displaying tibial
      shortening (median, 4.0 cm; mean, 4.6 cm; range, 3.0-12.0 cm) with various causes
      were treated with or without tibial osteotomy and stabilized using an Ilizarov
      lengthening apparatus. Postoperatively, lengthening of 1 to 1.5 mm/day was
      performed until the desired length was achieved. External fixation was then
      converted to internal fixation and either pure autogenous bone graft, or a
      mixture of autogenous and allogenous bone graft was supplemented.
      Postoperatively, protected weight bearing was advised until bony union was
      achieved. RESULTS: Eleven patients were followed up for a median of 3.4 years
      (mean, 4.0 years; range, 2.1-6.7 years) and solid union was achieved in all
      cases. Median external fixation occurred after 1.8 months (mean, 1.9 months;
      range, 1.2-4.5 months) and the median time until union after internal fixation
      was 4.5 months (mean, 4.8 months; range, 4-6 months). Two patients with rigid
      equinus feet required concomitant Achillis tendon lengthening. No other
      significant complications were noted. Classification of the results revealed that
      improvement from an unsatisfactory to a satisfactory outcome was achieved in all
      patients (p < 0.001). CONCLUSION: The described technique shortens the external
      fixation period and reduces patient suffering. Moreover, a high union rate and a
      low complication rate are achieved. Subjectively and objectively, patients can
      achieve satisfactory outcomes. Consequently, the described technique may be
      considered as an alternative to conventional techniques when indicated.

PMID- 12813339
TI  - The effect of femoral nailing on cerebral perfusion pressure in head-injured
      patients.
AB  - BACKGROUND: The timing of fracture fixation in patients with head trauma is
      controversial. Early fracture fixation may be associated with secondary brain
      injury. We undertook this study to investigate the effect of reamed
      intramedullary nailing on cerebral perfusion. METHODS: Seventeen patients were
      identified who had placement of an intracranial pressure monitor and reamed
      rodding of the femur. Retrospective chart review was performed. RESULTS: Average
      Injury Severity Score was 35 (range, 17-50). Cerebral perfusion pressure (CPP)
      decreased intraoperatively for all except one. The average decrease in CPP from
      pre- to intraoperative values was 17 mm Hg (p = 0.0012). Seventy percent had an
      average intraoperative CPP below 75 mm Hg, and all patients had a minimum CPP
      below 75 mm Hg. The decrease in CPP was mostly attributable to a corresponding
      decrease in mean arterial pressure. CONCLUSION: Patients with head trauma
      undergoing femoral rodding need careful attention paid to managing blood pressure
      to minimize CPP decreases.

PMID- 12813340
TI  - Early functional treatment versus early immobilization in tension of the
      musculotendinous unit after Achilles rupture repair: a prospective, randomized,
      clinical study.
AB  - BACKGROUND: The aim of our prospective, randomized, clinical study was to compare
      two postoperative regimens after Achilles rupture repair and determine whether
      early functional treatment will give a better result than early immobilization in
      tension of the musculotendinous unit. METHODS: Fifty patients with acute Achilles
      tendon rupture were randomized postoperatively to receive either early movement
      of the ankle between neutral and plantar flexion in a brace for 6 weeks or
      Achilles tendon immobilization in tension using a below-knee cast with the ankle
      in a neutral position for 6 weeks. Full weight bearing was allowed after 3 weeks
      in both groups. The patients were assessed clinically at 1, 3, 6, 12, and 24
      weeks, and the last control visit took place at a mean of 60 (SD 6.4) weeks
      postoperatively. RESULTS: The isokinetic calf muscle strength scores were
      excellent in 56%, good in 32%, fair in 8%, and poor in 4% of the patients in the
      early motion group at the last control checkup; whereas the scores in the cast
      group were excellent in 29%, good in 50%, and fair in 21% of the patients. The
      ankle performance scores were excellent or good in 88%, fair in 4%, and poor in
      8% of the patients in the early motion group, whereas the scores in the cast
      group were excellent or good in 92% and fair in 8% of the patients. At 3 months
      and at the last control checkup, no significant differences were seen between the
      two groups with regard to pain, stiffness, subjective calf muscle weakness,
      footwear restrictions, range of ankle motion, isokinetic calf muscle strength, or
      overall outcome. The complications included one rerupture in the early motion
      group and one deep infection and two reruptures in the cast group. Deep infection
      and the rerupture in the cast group occurred in the same patient. The outcome of
      the complications was good in two cases and poor in one. CONCLUSION: The
      isokinetic calf muscle strength results were somewhat better in the early motion
      group, whereas the other outcome results obtained in the two groups of patients
      were very similar. We recommend early functional postoperative treatment after
      Achilles rupture repair for athletes and well-motivated patients and for less
      motivated patients and nonathletes.

PMID- 12813341
TI  - The association between occupant restraint systems and risk of injury in frontal
      motor vehicle collisions.
AB  - BACKGROUND: An evaluation of seat belt use and airbag deployment, either alone or
      in combination, on risk of injury to specific body regions has yet to be
      completed. METHODS: A retrospective cohort study of front seat occupants involved
      in police-reported, tow-away, frontal motor vehicle collisions using data from
      the 1995 through 2000 National Automotive Sampling System was conducted. Only
      vehicles with a change in velocity (delta-V) of >/= 15 km/h were included. Risk
      of injury (Abbreviated Injury Scale score >/= 2) to specific body regions was
      compared according to seat belt use and airbag deployment. RESULTS: Compared with
      completely unrestrained occupants, those using a seat belt alone or in
      combination with an airbag had a reduced overall risk of injury (relative risk,
      0.42 and 0.71, respectively); no association was observed for those restrained
      with an airbag only (relative risk, 0.98). This pattern of results was similar
      for specific body regions with the exception of the lower extremity, wherein a
      significantly increased risk was observed for airbag deployment alone.
      CONCLUSION: Airbag deployment does not appear to significantly reduce the risk of
      injury either alone or in combination with seat belts. Airbag deployment without
      associated seat belt use may increase the risk of lower extremity injury.

PMID- 12813342
TI  - Rural prehospital trauma systems improve trauma outcome in low-income countries:
      a prospective study from North Iraq and Cambodia.
AB  - BACKGROUND: A five-year prospective study was conducted in North Iraq and
      Cambodia to test a model for rural prehospital trauma systems in low-income
      countries. RESULTS: From 1997 to 2001, 135 local paramedics and 5,200 lay First
      Responders were trained to provide in-field trauma care. The study population
      comprised 1,061 trauma victims with mean evacuation time 5.7 hours. The trauma
      mortality rate was reduced from pre-intervention level at 40% to 14.9% over the
      study period (95% CI for difference 17.2-33.0%). There was a reduction in trauma
      deaths from 23.9% in 1997 to 8.8% in 2001 (95% CI for difference 7.8-22.4%), and
      a corresponding significant improvement of treatment effect by year. The rate of
      infectious complications remained at 21.5 percent throughout the study period.
      CONCLUSION: Low-cost rural trauma systems have a significant impact on trauma
      mortality in low-income countries.

PMID- 12813343
TI  - Improving prehospital trauma care in rural areas of low-income countries.

PMID- 12813344
TI  - Trauma system evaluation using the fatality analysis reporting system.
AB  - BACKGROUND: The Fatality Analysis Reporting System (FARS) has recorded detailed
      data on fatal traffic crashes since 1975. At least three prior studies have used
      declining mortality rates derived from FARS as evidence of regional trauma system
      effectiveness. METHODS: FARS and census data were obtained at no cost through the
      Internet. Previously published studies were replicated graphically including data
      from additional years before and after the previously reported time periods, and
      with rates also calculated for control populations. RESULTS: The association of
      trauma system organization with observed decreases in mortality rates was less
      convincing when all available data were displayed and other potential factors
      were considered. Death after traffic crashes, and especially death in hospitals,
      is becoming less frequent throughout the country. CONCLUSION: FARS is an
      excellent resource available to all injury researchers, but provides little
      evidence that some regions have decreased traffic mortality more than others
      because of trauma systems.

PMID- 12813345
TI  - Differential angiogenic and proliferative activity of surgical and burn wound
      fluids.
AB  - BACKGROUND: Invasive surgical wounds exhibit the rapid production of a robustly
      proangiogenic environment. To compare the immediate angiogenic environment of
      wounds of different types, the angiogenic activity of fluid derived from burn
      injuries and wounds confined to the dermis was examined and compared with that of
      deeper surgical wounds. METHODS: The angiogenic activity of surgical wound fluid
      (SWF) (n = 7), skin graft wound fluid (SGF) (n = 3), and burn wound fluid (BWF)
      (n = 4) was assessed by measuring endothelial cell (EC) proliferative activity,
      EC chemotactic activity, and angiogenic activity in the rat corneal assay. The
      fibroblast growth factor-2 (FGF-2) level of each wound fluid was determined by
      enzyme-linked immunosorbent assay. RESULTS: SWF exhibited significant EC
      proliferative activity, SGF exhibited intermediate activity, and BWF displayed no
      EC proliferative activity. Seventy-one percent of SWF samples, 33% of SGF, and 0%
      of BWF contained significant EC chemotactic activity. Each wound fluid sample
      that demonstrated significant chemotactic activity also evoked a positive corneal
      angiogenic response. SWF contained 914 +/- 170 pg/mL of FGF-2, whereas SGF and
      BWF contained just 164 +/- 54 pg/mL and 37 +/- 7 pg/mL of FGF-2, respectively.
      CONCLUSION: The results suggest that injuries confined to the dermis, whether
      thermal or excisional, elicit a less robust initial angiogenic stimulus than deep
      surgical wounds.

PMID- 12813347
TI  - Segmental hepatic atrophy: a sequela of blunt intrahepatic bile duct injury.

PMID- 12813346
TI  - Dietary compounds inhibit proliferation and contraction of keloid and
      hypertrophic scar-derived fibroblasts in vitro: therapeutic implication for
      excessive scarring.
AB  - BACKGROUND: Keloid and hypertrophic scars commonly occur after injuries.
      Overproliferation of fibroblasts, overproduction of collagen, and contraction
      characterize these pathologic scars. Current treatment of excessive scars with
      intralesional corticosteroid injections used individually or in combination with
      other methods often have unsatisfactory outcome, frustrating both the patient and
      the clinician. The phytochemical compounds are well known as potential anticancer
      agents. We have investigated the inhibitory effects of compounds on keloid
      fibroblasts (KF) and hypertrophic scar-derived fibroblasts (HSF). METHODS:
      Fibroblasts were cultured from nontreated earlobe keloids and burn hypertrophic
      scars. Ten compounds (three hydroxybenzoic and four hydroxycinnamic acid
      derivatives, two flavonols [quercetin and kaempferol], and turmeric curcumin)
      were tested with fibroblasts. The inhibitory effects of compounds on fibroblasts
      was assessed by proliferation assays, fibroblast-populated collagen lattice
      (FPCL) contraction, and electron microscopy. RESULTS: The phytochemicals
      significantly inhibited KF and HSF proliferation in a dose- and time-dependent
      manner. In the hydroxybenzoic and flavonol groups, increasing inhibitory effects
      seemed to depend on increasing numbers of hydroxyl groups in their chemical
      structures. This phenomenon was not observed in the hydroxycinnamic acid group.
      The phytochemicals inhibited fibroblast proliferation by inducing cell growth
      arrest but not apoptosis. The reversibility of growth inhibition occurred when
      the compounds were removed from the culture and fresh media was replaced. Slower
      reversibility of growth inhibition was observed in the groups treated with
      quercetin, chlorogenic acid, or curcumin. The compounds quercetin, gallic acid,
      protocatechuic acid, and chlorogenic acid were the strongest inhibitors of FPLC
      contraction by HTFs. When the compounds were washed out of the lattices and
      replaced by fresh medium, the FPCL contraction was resumed. The resumption of
      FPCL contraction was slowest in the quercetin-treated group, indicating again the
      strong inhibitory effect of quercetin. CONCLUSION: From this in vitro study,
      quercetin seemed to have good potent effects to inhibit proliferation and
      contraction of excessive scar-derived fibroblasts.

PMID- 12813348
TI  - Nonoperative management of a penetrating colon injury: case report and review of
      the literature.

PMID- 12813349
TI  - Bilateral navicular body fractures.

PMID- 12813350
TI  - Air gun injuries to the abdominal aorta: report of two cases and review of the
      literature.

PMID- 12813351
TI  - Air gun pellet embolization to the right heart: case report and review of the
      literature.

PMID- 12813352
TI  - Air gun pellet cardiac injuries: case report and review of the literature.

PMID- 12813353
TI  - Development and injury of the triradiate cartilage with its effects on acetabular
      development: review of the literature.

PMID- 12813354
TI  - Use of modified wooden crutches as an adjunct in the radiographic evaluation of
      the cervical spine.

PMID- 12813355
TI  - Case of traumatic tension urohemothorax.

PMID- 12813356
TI  - Tension pneumothorax with pneumopericardium.

PMID- 12813357
TI  - Comment on "Low-dose ethanol alters the cardiovascular, metabolic, and
      respiratory compensation for severe blood loss".

PMID- 12813358
TI  - The utility of physical examination to detect hemopneumothorax in patients with
      blunt chest trauma.

PMID- 12813359
TI  - Statistical analyses of trauma outcome: when is more too much?

PMID- 12813360
TI  - Predictive value of monocyte histocompatibility leukocyte antigen-DR expression
      and plasma interleukin-4 and -10 levels in critically ill patients with sepsis.
AB  - It has been suggested that excessive activation of the anti-inflammatory pathways
      in sepsis may lead to poor outcome of patients with sepsis. The aim of this study
      was to test the value of histocompatibility leukocyte antigen (HLA)-DR-expression
      on blood monocytes and plasma levels of interleukin (IL)-4 and -10 in prediction
      of hospital mortality in patients with sepsis. Sixty-one critically ill patients
      with sepsis were prospectively enrolled to this study in two university hospital
      intensive care units. Survivors (n = 41) and nonsurvivors (n = 20) differed
      significantly in HLA-DR expression at admission: survivors' median 84%
      (interquartile range 64%-98%) versus nonsurvivors' median 62% (interquartile
      range 47%-83%, P = 0.025 by Mann-Whitney test). Similarly, the analysis revealed
      statistically significant differences between survivors and nonsurvivors in
      admission plasma IL-10 levels and in admission Sequential Organ Failure
      Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II
      scores, but not in IL-4 levels. The areas under receiver operating curves (AUC)
      showed that both monocyte HLA-DR expression and plasma IL-4 level showed poor
      discriminative power in prediction of hospital mortality (AUC < 0.70). Only IL-10
      levels on days 1 and 2 showed reasonable predictive power (AUCs 0.706 and 0.725,
      respectively). The highest AUC values were those of APACHE-II (0.786) and
      admission SOFA score (0.763). In conclusion, APACHE II and SOFA scores on
      admission showed better discriminatory power than HLA-DR expression and IL-10 and
      IL-4 levels in prediction of hospital mortality in critically ill patients with
      sepsis.

PMID- 12813361
TI  - A meta-analysis of controlled trials of anticoagulant therapies in patients with
      sepsis.
AB  - Although coagulation abnormalities may partly underlie the physiologic
      derangements of the sepsis syndrome, anticoagulant therapies have produced mixed
      results on survival in clinical studies. We hypothesized that a meta-analysis of
      clinical trials of anticoagulants in sepsis may provide insight as to the
      therapeutic utility of targeting the clotting cascade in this syndrome. We
      searched electronic databases and reviewed bibliographies of pertinent articles
      to identify controlled clinical studies in which anticoagulants had been
      administered as adjunctive therapy to patients with sepsis. After establishing
      statistical homogeneity, odds ratios (OR; with 95% confidence intervals [CI]) for
      effect of these agents on mortality and bleeding complications were determined
      using Mantel-Haenszel methodology. Potential for publication bias was assessed by
      the use of a statistical test of funnel plot asymmetry. Weighted linear
      regression was performed to examine the effect of control group mortality rate on
      treatment efficacy. We identified 11 studies that satisfied our inclusion
      criteria. Collectively, these studies enrolled 4690 patients (range of 29-2314)
      and examined three agents: antithrombin III (2659 patients), tissue factor
      pathway inhibitor (210 patients), and activated protein C (1821 patients). After
      establishing statistical homogeneity (P > 0.10, chi-square), we found that the OR
      (with 95% CI) for effect on mortality for these agents, relative to control
      treatment, was 0.8692 (0.7519-1.006). Weighted linear regression analysis was
      consistent with a control group mortality dependent effect for these agents (P =
      0.02). Only five of the studies reported bleeding complications. Pooling the
      results of these five studies (4376 patients) resulted in an OR (with 95% CI) of
      1.70 (1.40-2.07) relative to control treatment for bleeding risk. Anticoagulants
      as adjuvant therapy do not appear to improve outcome in sepsis and are associated
      with a significant risk of bleeding complications. To the extent that their
      treatment effect is dependent upon disease severity, the safety and efficacy of
      these agents may be enhanced by refinement in techniques of clinical
      stratification.

PMID- 12813362
TI  - Relative cytokine and cytokine inhibitor production by mononuclear cells and
      neutrophils.
AB  - Mononuclear cells represent the major source of cytokines in blood; however, it
      has been postulated that neutrophils may produce and/or release modest amounts of
      cytokines. In this study, we compared the production of cytokines and cytokine
      inhibitors in lipopolysaccharide (LPS)-stimulated whole blood, peripheral blood
      mononuclear cells (PBMCs), and neutrophils (PMNs) separated by density gradient
      centrifugation. Contamination of PBMCs in the isolated PMNs was less than 0.1% as
      determined by morphological analysis and flow cytometry. LPS (50 ng/mL) induced a
      strong increase of the proinflammatory cytokines tumor necrosis factor,
      interleukin (IL)-1beta, IL-8, and IL-6 in whole blood. In the isolated cell
      preparations, proinflammatory cytokine production was significantly greater in
      the PBMCs compared with the PMNs. On a per cell basis, PMNs produced less than
      1.5% of these cytokines compared with PBMCs. For cytokine inhibitors, TNF-soluble
      receptor type II and IL-1 receptor antagonist were increased by LPS stimulation
      in whole blood, PBMCs, and PMNs. On a per cell basis, LPS-induced TNF-soluble
      receptor type II and IL-1 receptor antagonist production by PMNs was 9.8% and
      15.4% of those of PBMCs, respectively. These data show that a highly purified
      population of PMNs makes a relatively minor to nonexistent contribution to the
      production of proinflammatory cytokines.

PMID- 12813363
TI  - Platelet-activating factor acetylhydrolase inhibits alveolar macrophage
      activation in vivo.
AB  - Platelet-activating factor (PAF) is an important proinflammatory mediator of
      septic shock. PAF is produced by activated macrophages and acts to perpetuate the
      response to endotoxin. PAF is metabolized by an endogenous PAF-acetylhydrolase
      (PAF-AH). Low circulating levels of PAF-AH have been associated with the
      development of postinjury multiple organ failure. We have previously shown that
      PAF-AH significantly inhibits macrophage activation by lipopolysaccharide (LPS)
      in vitro. The purpose of these studies was to determine whether this effect would
      translate to an in vivo model of remote lung injury. Wistar rats were
      administered a single intravenous dose of PAF-AH (5 mg/kg) or its carrier
      solution simultaneous with the induction of zymosan peritonitis. After 24 h,
      alveolar macrophages were obtained by bronchoalveolar lavage and stimulated in
      vitro with LPS (1 microg/mL). Supernatants were collected at 18 h for cytokine
      production and cellular and nuclear protein extractions were performed at 30 and
      60 min to assess the activation of p38 and extracellular signal-regulated kinase
      (ERK) 1/2 kinases and the nuclear translocation of nuclear factor (NF)-kappaB.
      Administration of PAF-AH significantly inhibited LPS-induced tumor necrosis
      factor alpha and interleukin-1beta production by alveolar macrophages from
      zymosan-treated animals. This functional inhibition was associated with
      inhibition of ERK 1/2 kinase and NF-kappaB activation but not p38 kinase
      activation. Interleukin 6 production was depressed in the macrophages from
      zymosan-treated animals but no additional inhibition resulted from PAF-AH
      treatment. In conclusion, zymosan peritonitis leads to priming of alveolar
      macrophages such that their subsequent tumor necrosis factor alpha response to
      LPS is enhanced. In vivo administration of PAF-AH abrogates this response,
      suggesting that this priming may be PAF dependent. This effect of PAF-AH may be
      mediated by the inhibition of intracellular signaling via inhibition of ERK
      kinase and NF-kappaB activation.

PMID- 12813364
TI  - Hypertonic saline resuscitation reduces apoptosis and tissue damage of the small
      intestine in a mouse model of hemorrhagic shock.
AB  - The effect of hypertonic saline resuscitation on intestinal damage and the
      incidence of apoptosis after hemorrhagic shock were investigated. After
      anesthesia, male BALB/c mice weighing 24-34 g were hemorrhaged to the mean
      arterial pressure of 40 +/- 5 mmHg for 90 min. Animals were randomly assigned to
      four groups: 1) resuscitation with 4 mL/kg of 7.5% NaCl (hypertonic saline; HS) +
      shed blood (SB); 2) resuscitation with two times the volume of shed blood of
      lactated Ringer's solution (2LR) + SB; 3) sham (catheter only); or 4) control (no
      treatment). Intestinal damage was graded based on the extent of the vacuolation
      at the basal area of the intestinal villi. Apoptosis of the small intestines was
      examined with the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5
      triphosphate nick-end labeling method and with DNA laddering. Caspase-3
      activation, heat shock protein (HSP) 70, and HSP40 were assessed by western
      blotting. Apoptosis of the small intestine and intestinal damage were
      significantly lower (P < 0.01) in the HS+SB group compared with the 2LR+SB group
      2 h and 6 h after hemorrhagic shock and resuscitation, respectively. This
      corresponded with more DNA fragmentation in the small intestine of the 2LR+SB
      group compared with the HS+SB group 2 h after hemorrhage and resuscitation. In
      addition, we observed less caspase-3 activation in the small intestine of the
      HS+SB group compared with the 2LR+SB group at 2 h after resuscitation. The
      content of HSP40 and HSP70 in the HS+SB group was similar to that in controls,
      but slightly decreased in the 2LR+SB group. HS resuscitation reduced intestinal
      damage and apoptosis after hemorrhagic shock, suggesting that HS resuscitation
      may improve the outcome after hemorrhagic shock by reducing apoptosis and damage
      to the small intestine.

PMID- 12813365
TI  - Effect of dose of hypertonic saline on its potential to prevent lung tissue
      damage in a mouse model of hemorrhagic shock.
AB  - Recent studies have shown that hypertonic saline (HS) resuscitation can reduce
      hemorrhage-induced lung damage by preventing neutrophil activation. In this
      study, we examined whether this protective effect can be improved by increasing
      the HS dose used for resuscitation. The protective effect of two HS doses was
      tested in a mouse model of hemorrhagic shock. BALB/c mice were bled to a mean
      arterial blood pressure of 35 +/- 5 mmHg for 1 h. Then the animals were
      resuscitated with lactated Ringer's (LR) or with HS (7.5% NaCl) at doses of 4
      mL/kg or 6 mL/kg body weight, sacrificed after 24 h, and lung tissue samples were
      collected. Evidence of lung injury was evaluated morphologically by scoring
      histology specimens in a blinded fashion. In a separate set of mice, plasma Na+
      and osmolarity were determined 15 min after resuscitation. Resuscitation of
      hemorrhaged mice with 4 and 6 mL/kg HS increased plasma Na+ concentrations by 5
      and 11 mM, respectively. LR treatment reduced plasma Na+ concentrations by 6 mM
      and resulted in a lung injury score of 6.1 +/- 0.8, accompanied by focal
      thickening of alveolar membranes, congestion, pulmonary edema, and interstitial
      and intra-alveolar neutrophil infiltration. HS at 4 mL/kg decreased focal
      thickening, congestion, pulmonary edema, and neutrophil infiltration, and the
      injury score to 3.8 +/- 0.9, which was not significantly different from controls
      (3.6 +/- 0.8), and lung damage was lowest in animals that received 6 mL/kg HS
      (2.5 +/- 0.2, P < 0.005 vs. LR). Lung damage scores inversely correlated with
      plasma Na+ concentrations (r > 0.9999). Our data suggest that the protective
      effect of HS may be a function of the plasma Na+ concentration and that HS at 6
      mL/kg is at least equally effective in reducing hemorrhage-induced lung damage
      compared to the more commonly used HS dose of 4 mL/kg.

PMID- 12813366
TI  - Role of endogenous interleukin-10 in local and distant organ injury after
      visceral ischemia-reperfusion.
AB  - The anti-inflammatory cytokine interleukin (IL)-10 has been detected in serum
      after visceral ischemia-reperfusion injury and exogenous IL-10 administration has
      been shown to attenuate the associated distant organ injury. This study was
      designed to examine the role that endogenous IL-10 production plays on both local
      and distant organ injury after visceral ischemia-reperfusion injury. Wild-type
      and IL-10(-/-)-null C57BL/6 mice were subjected to 20 min of supraceliac aortic
      occlusion or sham laparotomy. Serum and lung tissue cytokine levels (tumor
      necrosis factor alpha, IL-1beta, IL-6, KC/GRO, and IL-10) were measured after
      reperfusion (1, 2, and/or 4 h) using either enzyme-linked immunoassay or
      bioassay. Lung neutrophil infiltration and injury were quantified after
      reperfusion injury using myeloperoxidase concentration (2 h) and mean capillary
      permeability (4 h), respectively, whereas the direct liver injury was quantified
      with serum aspartate aminotransferase levels (1, 2, and 4 h). A subset of IL-10(
      /-)-null animals was administered human recombinant IL-10 before the visceral
      ischemia and lung MPO was measured after reperfusion (2 h). Visceral ischemia
      reperfusion in the wild-type and IL-10(-/-)-null mice was associated with in an
      increase in both serum (IL-1beta, KC/GRO, IL-6) and lung tissue (IL-1beta,
      KC/GRO) cytokine levels and resulted in lung neutrophil infiltration
      (myeloperoxidase), lung injury (mean capillary permeability) and liver injury
      (aspartate aminotransferase). The magnitude of the lung tissue cytokine response
      (IL-1beta, KC/GRO), neutrophil infiltration, and injury were greater in the IL
      10(-/-)-null mice. Exogenous IL-10 resulted in a decrease in the lung neutrophil
      infiltration in the IL-10(-/-)-null mice. The endogenous IL-10 response to
      visceral ischemia-reperfusion attenuates the associated lung neutrophil
      infiltration and injury but has no effect upon either the hepatic injury or the
      magnitude of the systemic inflammatory response. The beneficial effects of IL-10
      may be mediated by the inhibition of IL-1beta and KC/GRO through an endocrine
      rather than paracrine signal.

PMID- 12813367
TI  - Hypothermia induces interleukin-10 and attenuates injury in the lungs of
      endotoxemic rats.
AB  - We recently reported that hypothermia protects against intrapulmonary nitric
      oxide overproduction and nitric oxide-mediated lung injury in endotoxemic rats.
      Few studies have been performed to investigate whether hypothermia reduces
      inflammation by affecting favorable changes in chemokine and pro- and anti
      inflammatory cytokine profiles. In this study, we tested the hypothesis that
      hypothermia decreases concentrations of growth-related oncogene/cytokine-induced
      neutrophil chemoattractant-1 (GRO/CINC-1), interleukin (IL)-1beta, IL-6, and
      myeloperoxidase and increases concentration of IL-10 in the lungs endotoxemic
      rats. Twelve rats were anesthetized and randomized to treatment with either
      hypothermia (T = 18-24 degrees C; n = 6) or normothermia (T = 36-38 degrees C, n
      = 6). Endotoxin (15 mg/kg of Escherichia coli lipopolysaccharide) was
      administered intravascularly and lung tissue was harvested 150 min later. Three
      additional rats were sham instrumented and maintained as normothermic but not
      given endotoxin. Hematoxylin & eosin staining was performed for qualitative
      inspection of tissues. Quantitative analyses of lung homogenates were performed
      using enzyme-linked immunosorbent assays for IL-1beta, IL-6, IL-10, and GRO/CINC
      1. Myeloperoxidase concentrations were determined using a colorimetric assay.
      Hypothermia attenuated the induction of intrapulmonary IL-1beta (P < 0.05), IL-6
      (P < 0.05), GRO/CINC-1 (P < 0.05), and myeloperoxidase (P < 0.05) caused by
      endotoxin. Inspection of the lungs revealed that hypothermia similarly attenuated
      histological signs of injury, such as interstitial edema and neutrophil
      accumulation. Hypothermia increased the intrapulmonary concentration of IL-10
      more than 3-fold over that measured in the normothermia (endotoxin-exposed) group
      (P < 0.05). Hypothermia inhibits neutrophil recruitment in the lungs of
      endotoxemic rats in part by decreasing proinflammatory cytokine expression.
      Additionally, hypothermia induces intrapulmonary IL-10 expression. Further
      studies are needed to investigate whether IL-10 mediates the anti-inflammatory
      effects of hypothermia.

PMID- 12813368
TI  - Cepharanthin, an alkaloid from Stephania cepharantha, inhibits increased
      pulmonary vascular permeability in an ovine model of sepsis.
AB  - Sepsis is a life-threatening event when it occurs in patients suffering from
      smoke inhalation injury. Pneumonia is one of the most frequent sources of
      infection in sepsis. Activated leukocytes likely play a role in the pathogenesis
      of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the
      activation of neutrophils. In this study, we investigated the effects of
      cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n
      = 15) were surgically prepared for the study. After 5 days recovery from the
      operative procedures, tracheostomy was performed in all animals and 48 breaths of
      cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane
      anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was
      instilled into the airway using a bronchoscope. All of the animals were
      mechanically ventilated with 100% O(2). Cepharanthin (1.3 mg/kg/h) was infused in
      five sheep continuously beginning 1 h after the insult and thereafter for the
      remainder of the 24-h study period. Control animals (n = 6) were treated with 5%
      dextrose as a vehicle control. Cepharanthin significantly attenuated changes in
      lung histology as well as in lung wet/dry weight ratio. An in vitro study
      revealed that cepharanthin inhibited the release of neutrophil elastase from
      isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine
      (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin
      also inhibited the fMLP-induced increase in intracellular calcium levels of
      neutrophils. This result indicates cepharanthin inhibits protein kinase C or a
      more downstream signaling pathway in neutrophil activation. In conclusion,
      cepharanthin attenuates acute lung injury and septic shock after smoke inhalation
      in sheep.

PMID- 12813369
TI  - Iron overload before cecal ligation and puncture increases mortality.
AB  - Iron metabolism is dysregulated in critically ill patients. A mouse model of
      dysregulated iron metabolism was used to examine the consequence of iron loading
      upon sepsis. Mice deleted in the hfe gene (hfe-/-) abnormally accumulate iron in
      tissue; defects in the human hfe gene are clinically expressed as
      hemochromatosis. Hfe-/- mice and wild-type counterparts were randomized to
      receive either high- or low-iron diets for 2 weeks. After iron loading, mice were
      subjected to cecal ligation and puncture (CLP), a clinically relevant animal
      model of intra-abdominal sepsis. A preliminary (but underpowered) study suggested
      that iron-loaded hfe-/- mice had increased mortality as compared with hfe-/- mice
      fed a low-iron diet. There was no difference between wild-type and hfe-/- mice
      fed a low-iron diet or between wild-type mice fed hihg- and low-iron diets. A
      subsequent, appropriately powered study showed that iron-loaded hfe-/- mice had
      significantly higher mortality from intra-abdominal sepsis than hfe-/- mice fed a
      low-iron diet. Iron loading was confirmed through chemical assay of iron
      concentration in hepatic tissue. Animals with dysregulated iron handling, loaded
      with iron and subjected to CLP, had double the mortality of animals with normal
      iron levels. Critical care patients often have altered iron metabolism. In
      clinical practice, critically ill patients may receive iron through direct
      administration and the transfusion of blood products. Iron therapy may adversely
      affect the clinical outcome from sepsis.

PMID- 12813370
TI  - Peroxisome proliferator-activated receptor-gamma agonists modulate macrophage
      activation by gram-negative and gram-positive bacterial stimuli.
AB  - Bacterial products, such as lipopolysaccharide (LPS) or heat-killed Escherichia
      coli (EC), and heat-killed Staphylococcus aureus (SA) are potent activators of
      macrophages (MO). When stimulated by these bacterial components, MO produce
      inflammatory mediators, such as nitric oxide (NO) and thromboxane (Tx) B(2).
      Bacterial mediator production is preceded by the activation of various signal
      transduction pathways. Agonists that activate the peroxisome proliferator
      activated receptor-gamma (PPARgamma) have been shown to block MO mediator
      production by LPS and other stimuli. However, very little is known about the
      effects of PPARgamma agonists on SA- or EC-induced MO activation. Therefore, we
      investigated whether the PPARgamma agonists 15-deoxy-Delta12,14 prostaglandin
      J(2) (15-PGJ(2)) and troglitazone block LPS-, EC-, or SA-induced mediator
      production. Rat peritoneal MO were stimulated with LPS, EC, or SA (10 microg/mL)
      with or without increasing concentrations (0.1 to 10 microM) of each PPARgamma
      agonist and NO and TxB(2) production were measured. 15-PGJ(2) decreased LPS-, EC
      , and SA-induced NO and TxB(2) production. However, troglitazone only inhibited
      the production of TxB(2) by each stimuli. In parallel studies, the effects of
      PPARgamma agonists on signaling pathways were evaluated. Rat peritoneal MO were
      pretreated for 1 h with 15-PGJ(2) or troglitazone (1 or 10 microM) and then
      stimulated for 40 min with LPS, EC, or SA (10 microg/mL). Western blot analysis
      demonstrated that 15-PGJ(2) significantly inhibited LPS-, EC-, and SA-induced ERK
      (1/2) activation and blocked IkappaBalpha degradation. Troglitazone had no
      significant effect on either signaling protein. The data demonstrate that
      although both 15-PGJ(2) and troglitazone are considered PPARgamma agonists, they
      differentially affect mediator production and cell signaling events. PPARgamma
      independent effects of 15-PGJ(2) may contribute to its more potent anti
      inflammatory effects compared with troglitazone.

PMID- 12813372
TI  - Decreased lymphocyte apoptosis by anti-tumor necrosis factor antibody in Peyer's
      patches after severe burn.
AB  - Severe burn results in immunosuppression, with increased lymphocyte apoptosis in
      both the central and peripheral immune system. As atrophy of the small intestine
      has been described in mouse models and intestinal lymphocytes have been
      implicated in the burn inflammatory response, we examined the effects of burn and
      tumor necrosis factor (TNF)-alpha on lymphocytes in intestinal Peyer's patches.
      Anesthetized C57BL6 mice received a 30% full-thickness scald burn on the upper
      back. Sham-burned animals served as controls. Anti-TNF or control immunoglobulin
      (Ig) G antibody (200 microg) was given immediately after the burn. The animals
      were initially resuscitated with 2 mL of normal saline, and were then sacrificed
      12 h postburn. Terminal deoxyuridine nick-end labeling (TUNEL) and proliferative
      cell nuclear antigen (PCNA) staining was performed. Apoptosis was quantified as
      apoptotic lymphocytes/high-powered field (hpf). Results, expressed as mean +/-
      SEM, were compared using analysis of variance (ANOVA) and the Student-Newman
      Keuls test. All mice survived the burn. An initial time-course experiment
      demonstrated maximal Peyer's patch apoptosis 12 h after the burn. Sham mice had
      25 +/- 7 TUNEL-stained cells/hpf in Peyer's patches, whereas burned mice had 93
      +/- 18 cells/hpf (P < 0.05). In contrast, burned mice receiving anti-TNF antibody
      had 28 +/- 8 TUNEL-stained cells/hpf (P < 0.05 vs. burn), whereas sham mice
      receiving anti-TNF antibody had 20 +/- 4 cells/hpf. There were no significant
      differences in PCNA staining between the groups. Scald burn results in lymphocyte
      apoptosis in Peyer's patches. This apoptosis can be abrogated by the addition of
      anti-TNF antibody. Apoptotic changes may lead to the failure of the intestinal
      immunological barrier and increased risk of sepsis.

PMID- 12813371
TI  - Effects of ketamine/xylazine on expression of tumor necrosis factor-alpha,
      inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa
      during endotoxemia.
AB  - Some anesthetics attenuate expression of endotoxin-induced production of
      proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X)
      decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the
      effects of K/X on gut function and gene expression are unknown. The purpose of
      this study was to examine the effect of K/X on LPS-induced gastric fluid
      accumulation, and gastric tumor necrosis factor (TNF)-alpha, inducible nitric
      oxide synthase (iNOS), and cyclo-oxygenase (COX)-2 expression, as well as serum
      TNF-alpha protein levels over time. We hypothesized that K/X would attenuate
      these LPS-induced endpoints. Rats were given either intraperitoneal saline or K
      (70 mg/kg) and X (6 mg/kg) 1 h before saline or LPS (20 mg/kg i.p.) treatment of
      1, 3, or 5 h. Serum and gastric fluid and mucosa were collected and TNF-alpha,
      iNOS, and COX-2 expression were determined. LPS caused a significant increase in
      early serum and gastric mucosal TNF-alpha protein expression at 1 h, an effect
      that was significantly attenuated by K/X pretreatment. LPS caused significant
      gastric stasis and increased iNOS and COX-2 mRNA expression and iNOS protein
      expression in the stomach when compared with controls. K/X attenuated LPS-induced
      gastric fluid accumulation and upregulation of iNOS mRNA and protein, but not COX
      2. These data indicate that K/X inhibits some proinflammatory genes and
      pathophysiologic responses in the serum and stomach during endotoxemia. The
      effects of K/X appear to inhibit transcriptional events in iNOS expression, which
      may be dependent on K/X-induced inhibition of early TNF-alpha expression.
      Furthermore, in rat models of endotoxemia, especially those evaluating the
      stomach, careful consideration needs to be given if anesthetic combinations with
      ketamine and/or xylazine are used, as they alter LPS-induced responses.

PMID- 12813373
TI  - The septic abscess wall: a cytokine-generating organ associated with portal
      venous cytokinemia, hepatic outflow fibrosis, sinusoidal congestion, inflammatory
      cell sequestration, hepatocellular lipid deposition, and focal cell death.
AB  - An acute septic inflammatory response with access to the portal circulation was
      created in a rat model using an intra-abdominal abscess composed of a sterile
      agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109
      Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed
      intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA
      by in situ hybridization. Portal venous blood draining into the liver from the
      intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 in
      both sterile and septic groups compared with a control normal animal group.
      Increased levels of these cytokines were also found in suprahepatic inferior vena
      caval blood, but were correlated with the higher portal vein levels, suggesting a
      gradient from abscess wall to portal vein into the systemic circulation via the
      liver. Liver histology demonstrated sinusoidal congestion centering on the
      central vein, growing worse with progression from normal in control, to sterile,
      to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive
      inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis
      also increased from control, to sterile, to septic. Gene expression by in situ
      hybridization demonstrated a significant increase in IL-6 and fibrinogen mRNAs in
      cells surrounding the central vein in sterile and septic animals, being greatest
      in animals with sepsis, associated with an increased deposition of collagen in
      the central vein area, most prominent in the septic liver. The pericentral vein
      cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells
      containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic
      animals, respectively. The data suggest that an intra-abdominal abscess,
      especially when contaminated with gram-negative bacteria, induces mRNA-generated
      cytokine responses in the abscess wall that are related to increased portal
      venous levels of the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6
      perfusing the liver. These, in turn, induce localized production of IL-6 and
      fibrinogen mRNAs in cells at the central vein area with resultant outflow
      fibrosis and increased inflammatory cell sequestration within the liver lobular
      sinuses. This is associated with a generalized inflammatory response and
      intrahepatic portal sinusoid congestion. There is also increased hepatocellular
      lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall
      itself appears to be a major mediator of the septic hepatic response.

PMID- 12813374
TI  - Influence of steroids on oxidant generation in activated human granulocytes and
      mononuclear leukocytes.
AB  - Steroids, in particular, 17beta-estradiol (E(2)), have been reported to improve
      the response to trauma in animal models. In these models, the leukocyte plays a
      critical role in the inflammatory cascade. We examined the affects of E(2),
      hydrocortisone (H), progesterone (P(4)), and E(2) with P(4) on oxidant production
      in human granulocytes (PMNs) and mononuclear leukocytes (MNCs). Each cell type
      was loaded with 2,7-dichlorodihydrofluorescein and then simultaneously activated
      with human cytokines (tumor necrosis factor alpha, interleukin-1beta, and
      interferon gamma) and hemoglobin and inhibited with and without equimolar
      concentrations of each steroid treatment or nitric oxide (NO) synthesis
      inhibitors. After incubations of 1 or 5 h, intracellular oxidants were quantified
      by flow cytometry. Activation by cytokines combined with hemoglobin, resulted in
      a 450-575% increase in oxidant production that was synergistically greater than
      the sum of either component alone. Pharmacological levels of E(2) decreased
      oxidants in MNCs at 1 h. In contrast at 5 h, H decreased oxidants more than E(2).
      The addition of P(4) to E(2) concentrations almost eliminated oxidants from 1 h
      activated MNCs. None of the steroids significantly reduced oxidants in PMNs,
      suggesting that the E(2) effect on MNCs was not caused by its nonreceptor
      mediated antioxidant properties. Because L-NMMA inhibited at least 55% of the
      total oxidants, part of E(2) dampening effects would be attributed to NO. These
      results suggest that steroid-attenuated MNC-derived NO may reduce autocrine and
      paracrine effects on inflammation if appropriate doses of steroids are given soon
      after injury.

PMID- 12813375
TI  - Intraperitoneal microdialysis (IPM): a new technique for monitoring intestinal
      ischemia studied in a porcine model.
AB  - Acute mesenteric thrombosis, vascular complications of intestinal
      transplantation, sepsis, and multiple organ failure are all associated with
      intestinal ischemia. To improve the outcome of these patients, better monitoring
      devices are needed. A new technique, intraperitoneal microdialysis (IPM), was
      evaluated for detection of intestinal ischemia in a porcine model, with the
      intention of evaluating the technique for future use on humans. Fourteen pigs
      divided into two studies were used. In a total ischemia study a microdialysis
      catheter was placed intraperitoneally and the superior mesenteric artery was
      occluded for 1 h 40 min. In a local ischemia study, the arcus vessels supplying a
      30-cm long small bowel segment were occluded for 3 h 20 min. One IPM catheter was
      placed next to the ischemic area and another IPM catheter 10 cm caudally as an
      intraperitoneal reference. In both studies reference catheters were placed
      subcutaneously. Glucose, lactate, pyruvate, and glycerol were analyzed every 20
      min. In both studies vessel occlusion resulted in decreased glucose and increased
      lactate, glycerol, and lactate/pyruvate ratio. Significant changes were reached
      after 60 min of ischemia in most analytes, whereas the values from the reference
      catheter were stable. Our conclusion is that intestinal ischemia is detectable
      with IPM based on the analysis of well-documented markers of ischemia (increased
      lactate/pyruvate ratio) and cell membrane damage (elevated glycerol levels). It
      allows semi-continuous monitoring of the intestines with a minimally invasive
      procedure, which we believe will be possible to apply in human routine clinical
      use.

PMID- 12813376
TI  - Mitral valve repair in the elderly: operative risk for patients over 70 years of
      age is acceptable.
AB  - AIM: Mitral valve repair for degenerative disease is widely accepted. Because of
      low risk and excellent late outcomes, surgical intervention is recommended
      increasingly early when repair appears possible. The place of repair vis a vis
      continued medical therapy in the elderly, however, is less well defined as there
      are scant data on their surgical risk. We reviewed our recent results with mitral
      valvuloplasty for degenerative disease with attention to the influence of age.
      METHODS: Thirty-day results of mitral valvuloplasty for degenerative disease
      between January 1996 and April 2000 were examined retrospectively. Patients with
      ischemic etiology were excluded. Results among those over age 70 years were
      compared with younger patients. RESULTS: Of 140 patients (78 men and 62 women)
      aged 27 to 91 (mean 62+/-13) years (44 gs;70 years of age), 61 underwent isolated
      mitral valvuloplasty, 71 mitral valvuloplasty and coronary artery bypass, and 8
      mitral valvuloplasty with other procedures. By multivariate analysis preoperative
      cardiogenic shock (0.001), but not age, was as a risk factor for death. Among
      patients stratified by age gs; or <70, there were differences in atrial
      fibrillation (47.7% vs 29.2%, p=0.03), prolonged ventilation (31.8% vs 15.6%,
      p=0.03) and hospital stay (median 9.5, range 5-285 vs median 6.5, range 2-36,
      p=0.001), but not 30-day readmission (15.9% vs 22.9%) or death (5.2% vs 9.1%,
      p=0.49). CONCLUSION: Operative results for mitral valvuloplasty in the elderly
      are acceptable. Surgery should not be withheld on the basis of age alone.

PMID- 12813377
TI  - Economic impact of mitral valve plasty versus replacement for mitral valve
      insufficiency.
AB  - AIM: The principal techniques for surgical correction of mitral valve
      regurgitation (MR) were compared, with emphasis on the economic impact. METHODS:
      In a prospective non-randomized study 225 patients undergoing mitral valve repair
      were analyzed, 75 had mitral valve plasty (MVP) and 150 had mitral valve
      replacement (MVR). Patient demographics showed no group differences. RESULTS:
      Cardiopulmonary bypass time and ischemia time were shorter in the MVP-group,
      p<0.0001. Hospital mortality was lower after MVP, 2.0% (3/150) compared to MVR,
      6.7% (5/75). ICU-stay was shorter in the MVP-group and so was length of
      postoperative hospital stay, p=0.014. Urgent operation was the only significant
      risk factor for mortality after MVP. Re-operation, endocarditis, grade IV MR, and
      NYHA class IV were additional risk factors in the MVR-group. Postoperative
      improvements of NYHA and mitral valve function were similar in both groups. MVP
      was more cost effective than MVR (18,050 USD or 20,430 Euro versus 24,824 USD or
      28,097 Euro, p<0.001). CONCLUSION: Mitral valve plasty for MR is efficient and
      associated with shorter CPB and ischemia times as well as length of stay in ICU,
      together with a lower device cost, which makes MVP more cost effective than MVR.

PMID- 12813378
TI  - Off-pump versus on-pump coronary bypass. Comparison of patient characteristics
      and early outcomes.
AB  - AIM: This clinical report details a comparison between the conventional on-pump
      and beating heart off-pump techniques with particular attention to patient
      characteristics, perioperative variables and early outcomes. METHODS: We
      collected prospectively a comprehensive data body from 1131 consecutive patients
      who underwent isolated CABG in Tampere University Hospital. The morbidity,
      mortality and length of stay data from the secondary referral hospitals were also
      collected. One thousand and sixteen (89.8%) patients underwent bypass grafting
      with cardiopulmonary bypass (CPB, on-pump) and 115 (10.2%) patients without the
      CPB (off-pump). RESULTS: Thirty-day mortality rates were 4.0% (on-pump) and 2.6%
      (off-pump, p=0.5). The total postoperative length of stay was 12 (on-pump) and 10
      (off-pump) days as the medians (p<0.001). Adverse outcome events among the on
      pump and off-pump patients were as follows: postoperative stroke, 2.5% and 0.9%
      (p=0.3); perioperative myocardial infarction, 7.0% and 7.8% (p=0.7); impaired
      renal function, 9.5% and 4.3% (p=0.3); re-sternotomy for bleeding or low output,
      5.3% and 4.3% (p=0.2); new-onset atrial fibrillation, 38.9% and 24.6% (p=0.002)
      and the need for red cell transfusions in ICU, 50.3% and 22.6% (p<0.001). Eighty
      three percent of the on-pump and 85.2% of the off-pump patients (p=0.5) had a
      favorable outcome without a major complication. CONCLUSION: Considering the
      limitations with a nonrandomized study design, we conclude that off-pump CABG is
      a safe and comparable method of myocardial revascularization in terms of early
      outcomes. Overall length of stay shorter by 2 days, over a third shorter
      ventilation time, fewer red cell transfusions and lower frequency of
      postoperative atrial fibrillation favor off-pump surgery.

PMID- 12813380
TI  - Prospective randomized comparison between redon catheters and chest tubes in
      drainage after cardiac surgery.
AB  - AIM: To compare in a prospective randomized study chest tube (CT) and redon
      drains (RD) for effectiveness, cost, pain and complications after heart surgery
      using cardiopulmonary bypass. METHODS: Forty patients undergoing heart surgery
      were analyzed prospectively. Twenty patients had small RD with strong (-700 mmHg)
      vacuum and 20 others standard CT. All patients had patient controlled analgesia
      in the postoperative period and pain was noted. Residual pericardial effusion
      (RPE) was controlled and quantified at postoperative day 7 with transthoracic
      echocardiography. Drainage complications were noted and compared in both groups.
      RESULTS: Surgical statistics were comparable in both groups. Two patients
      underwent reoperation in CT for clotting, and 1 in RD for active surgical
      bleeding. One patient had orifice infection in CT. Drainage volumes and times
      were comparable in both groups at removal (992+/-507 ml in RD, 1154+/-571 ml in
      CT, p=ns). Morphine consumption and pain estimation were comparable in both
      groups in the postoperative period and at drainage removal. Echographic control
      showed important RPE for 3 patients in both groups. System cost was higher in CT
      compared to RD (up to 7 times). CONCLUSION: RD are comparable to CT in terms of
      drainage, pain and complications. Nevertheless, they offer better handling and
      removal conditions and limited cost.

PMID- 12813379
TI  - Implantation of the coronary arteries after reconstruction of the neoaorta by
      using pericardial or pulmonary hood techniques. A significant impact on the
      outcome of arterial switch operations.
AB  - AIM: Coronary artery anomaly and techniques used for their transfer are the major
      risk factors for the arterial switch operation. Although various methods have
      been described, torsion and stretching of the coronary arteries continue to
      trouble surgeons. Especially, in cases in which there is a size mismatch between
      the aorta and the pulmonary artery, the true coronary implantation points can
      change. METHODS: We studied the incidence of myocardial ischemia in 40 patients
      who underwent a Jatene procedure from January 1997 to August 2000 at Istanbul
      Medical Faculty of Istanbul University. In all cases; firstly, the neo-aortic
      anastomosis was performed. After filling the neo-aorta by removing the aortic
      cross-clamp, we aimed to identify the exact coronary implantation points. In 26
      cases, direct re-implantation or trap-door techniques were the method of choice
      used for the implantation. In 14 cases, we used pericardial or pulmonary hood
      augmentation techniques. In 12 of these 14 cases, we used directly pericardial or
      pulmonary hood for the maintenance of the exact coronary geometry because of the
      unfavorable anatomy. In the remaining 2 patients, because of the determination of
      ischemic changes on the electrocardiogram during the rewarming phase, we should
      revise the coronary anastomosis by a pericardial hood. RESULTS: One patient with
      intramural course of the coronary arteries died from of myocardial ischemia. In
      the remaining 39 patients, we did not see postoperative morbidity and mortality
      because of the myocardial ischemia. CONCLUSION: The use of pericardial or
      pulmonary hood augmentation techniques is very helpful for the maintenance of the
      exact coronary geometry. Reconstruction of the neoaorta prior to coronary
      anastomosis allows a more accurate determination of the true coronary
      implantation points; especially, if there is an abnormal relationship and size
      mismatch between the great vessels. By this innovative technique, the more
      accurate geometry and angulation of the coronary arteries can be achieved.

PMID- 12813381
TI  - Heat shock protein 60 expression in patients undergoing cardiac operations.
AB  - AIM: Cardiomyocytes respond to stress with the expression of different heat shock
      proteins (HSP). The mitochondrial HSP60 is known to be expressed by various
      stress factors, including ischemia and reperfusion. The aim of this study was to
      investigate if HSP60 is increased in human myocardium after cardiac surgery.
      METHODS: To determine if heat shock protein 60 accumulated in the myocardium of
      patients undergoing car-diac operations, right atrial samples before and after
      extracorporeal circulation were excised and immediately frozen in liquid
      nitrogen. PATIENTS: we obtained 10 sequential right atrial specimens from 5 male
      patients in sinus rhythm undergoing elective cardiac surgery. MEASURES: the HSP60
      protein level was determined by SDS-PAGE, Western blot and quantified by optical
      densitometry according to the immunoreactive bands of actin. RESULTS: The HSP60
      concentration was unchanged in hearts after a single episode of hypothermic
      ischemia and reperfusion. Immunoblot analysis demonstrated HSP60 expression in
      all hearts. There was no correlation with the endurance of cardiopulmonary bypass
      or reperfusion time. CONCLUSION: These findings indicate that myocardial HSP60 of
      patients undergoing cardiac operations is not increased after an obligatory
      period of ischemia, cardioplegic arrest and reperfusion. This might reflect an
      effective cardioprotection during ECC.

PMID- 12813382
TI  - Do we still need CK-MB in coronary artery bypass grafting surgery?
AB  - AIM: The aim of this study was to evaluate the role of cardiac Troponin I (cTnI)
      and CK-MB for early prediction of outcome of patients undergoing coronary artery
      bypass grafting (CABG) surgery. METHODS: In 134 consecutive patients undergoing
      CABG-surgery blood samples were analyzed for cTnI concentration and CK-MB
      activity. ECG, hemodynamic parameters and the need for inotropic support, were
      continuously registered. Patients were divided into group A (uneventful course),
      group B (ischemia by ECG, hemodynamic stability) and group C (ischemia by ECG and
      IABP). RESULTS: After removal of X-clamp an increase cTnI and CK-MB was observed
      in all patients. Five hrs after stop of CPB group A (8.3+/-4.2 microg/L) had
      lower cTnI values compared to group B (14.8+/-5.3 microg/L) (p=0.035) and C (54+/
      22.8 microg/L) (p=0.023). The cut off value was 14.8 microg/L. Sensitivity and
      specificity (99%/97%) was higher for cTnI than for CK-MB (90%/30%). The positive
      predictive value of outcome was better for cTnI (86%) than for CK-MB (33%).
      CONCLUSION: CTnI is a specific and sensitive marker for evaluation of
      perioperative myocardial ischemia (PMI). Additional determination of CK-MB
      activity does not provide further clinical information. CTnI should be the marker
      of first choice in CABG surgery.

PMID- 12813383
TI  - Does leukodepletion during elective cardiac surgery really influence the overall
      clinical outcome?
AB  - AIM: We examined the impact of leukocyte filtration during the entire bypass time
      on postoperative leukocytosis, perioperative hemorrhage and overall clinical
      outcome in patients undergoing elective cardiac surgery. METHODS: Eighty patients
      who electively underwent cardiac surgery were randomly allocated to a leukocyte
      depletion group (n=40) or a control group (n=40). In patients of the leukocyte
      depletion group an arterial line filter with leukocyte depleting capacity (Pall
      LG6) was applied instead of a standard arterial line filter. White blood cells
      and platelet count were estimated preoperatively and at various times
      postoperatively. Postoperative clinical outcomes were also recorded. RESULTS:
      Repeated measure analysis of variance between groups showed that leukocyte counts
      were significantly lower in the depletion group postoperatively (p=0.005) whereas
      no difference was found in the platelet counts (p=0.37). The catecholamine dose
      required at the time of weaning from cardiopulmonary bypass and during the first
      12 postoperative hours was found to be lower in the leukodepletion group (p=0.027
      and p=0.021, respectively). Furthermore leukodepleted patients showed a transient
      improvement in the oxygenation index (p=0.029) and a shorter period of mechanical
      ventilation (p<0.001). The incidences of postoperative complications were similar
      between the groups. No difference was observed in regard to postoperative blood
      loss (p=0.821) and amount of packed red blood cells required for transfusion
      during the first 24 hours (p=0.846). The duration of intensive care unit stay and
      of hospitalization were similar between the groups. CONCLUSION: Leukocyte
      depletion contributes to early postoperative improvement in heart and lung
      function but does not influence significantly the overall clinical outcome of
      patients undergoing elective cardiac surgery.

PMID- 12813385
TI  - Spontaneous recanalization of functionally occluded bilateral internal thoracic
      artery T graft.
AB  - Functional occlusion of the left internal thoracic artery T graft is reported.
      The patient underwent triple coronary artery bypass grafting with bilateral
      internal thoracic artery, anastomosing in situ to the left internal thoracic
      artery to the left anterior descending artery, free right internal thoracic
      artery to the obtuse marginal and posterolateral branch of the left circumflex
      artery. Early angiography showed occlusion of the in situ left internal thoracic
      artery to the moderately stenosed left anterior descending artery and patent side
      arm to circumflex. However, mid-term angiography revealed restoration of the left
      internal thoracic artery flow. A negative exercise stress test was noted
      throughout the postoperative period. Flow competition with a native coronary
      artery may be responsible for functional occlusion of the left internal thoracic
      artery.

PMID- 12813384
TI  - Tranexamic acid reduces bleeding after off-pump coronary artery bypass grafting.
AB  - AIM: To assess the ability of tranexamic acid, compared with an untreated control
      group, to decrease bleeding and transfusion requirements in patients undergoing
      coronary artery bypass grafting on the beating heart. METHODS: Forty-nine
      randomly selected patients were enrolled to elective coronary artery bypass
      grafting without the use of cardiopulmonary bypass. Of these, 23 received
      tranexamic acid (bolus of 1 g before surgical incision, followed by infusion 200
      mg/hour during surgery) and 26 patients were enrolled into a control group.
      Preoperative hematological variables, postoperative blood loss at 4 and 24 hours,
      transfusion requirements of packed red blood cells,and postoperative thrombotic
      events such as a myocardial infarction, stroke and pulmonary embolism were
      recorded. RESULTS: The two groups were similar in terms of patients'
      characteristics. Postoperative bleeding was significantly lower in the tranexamic
      acid group compared with the control group (median [25th-75th percentiles]): 115
      [92-148] vs 230 [170-260] mL at 4 hours, p<0.001; 420 [330-523] vs 550 [500-650]
      mL at 24 hours, p<0.01). Transfusion requirements were lower in the tranexamic
      acid group compared with the control group (RBC 9% vs 28%), but the difference
      was not statistically significant. Treatment with tranexamic acid was not
      associated with a higher incidence of myocardial ischemia or other thrombotic
      events. CONCLUSION: Tranexamic acid reduces postoperative blood loss after
      coronary artery bypass grafting on the beating heart. Evaluation of transfusion
      requirements warrants further study.

PMID- 12813386
TI  - De Vega's tricuspid annuloplasty for Ebstein's anomaly.
AB  - A case of Ebstein's anomaly as demonstrated by echocardiography and
      electrophysiological studies is discussed. In view of deterioration in tricuspid
      regurgitation and right ventricular dysfunction, successful surgical repair
      employing De Vega's tricuspid annuloplasty along with plication of the atrialised
      portion of the right ventricle is described. Intraoperative transesophageal
      echocardiography following the procedure revealed satisfactory repair and a
      significant decrease in tricuspid regurgitation. This simple technique appears to
      be effective in patients having anterior leaflet sufficiently large area and
      motion. Adequate long-term follow-up in a large series of patients is essential
      to confirm that it is also beneficial and durable.

PMID- 12813387
TI  - Off-pump coronary artery revascularization: ideal indication for patients with
      porcelain aorta and calcification of great vessels.
AB  - Patients with porcelain aorta and severe calcification of the great vessels are a
      challenging dilemma for the cardiovascular surgeon regarding bypass technique,
      choice of conduit, and selection of proximal anastomotic sites due to the high
      incidence of devastating thromboembolization and aortic injury. No currently
      proposed surgical approach avoids manipulation of the heavily calcified ascending
      aorta. Three patients presented with unstable angina and decreased ventricular
      function secondary to significant left main coronary artery stenosis and 3-vessel
      coronary artery disease. In addition to the coronary artery disease, severely
      calcified ascending aorta and great vessels were discovered. One patient
      presented with near total distal abdominal aortic occlusion, severe peripheral
      vascular disease, history of stroke, and carotid endarterectomy. Surgical
      coronary revascularization was indicated. Coronary artery bypass grafting using
      internal thoracic artery and greater saphenous vein composite arterial inflow
      grafts in combination with off-pump beating heart surgery was successfully used.
      Cardiopulmonary bypass and clamping of the aorta was avoided. No new neurologic
      deficit was observed. Coronary revascularization with internal thoracic artery
      composite grafts and avoiding cardiopulmonary bypass and clamping the calcified
      aorta is an effective method to prevent clamp injury and thromboembolization. Off
      pump coronary artery bypass grafting seems to be an ideal indication in patients
      with porcelain aorta because the surgical techniques of "no-touch" and "no
      cannulation" can be applied.

PMID- 12813388
TI  - A simple less invasive method of radial artery harvesting in coronary artery
      surgery.
AB  - A simple, less invasive radial artery harvesting technique involving small skin
      incisions is described. Only 2 retractors, one of which is light-sourced, are
      required to construct the operating field. Full harvesting can be accomplished
      under direct vision with a long-bladed low-voltage electrocautery and forceps
      through 3 small skin incisions on the forearm. The time required for the
      harvesting is no longer than that of the standard technique. Spasm of the radial
      artery has not been seen. Esthetic results are satisfactory.

PMID- 12813389
TI  - A novel technique for the repair of complete atrioventricular septal defects:
      simplified 2-patch technique.
AB  - Today complete atrioventricular septal defects can be corrected with acceptable
      mortality and postoperative morbidity. Although opinions still differ regarding
      the most appropriate method of choice, some surgeons have proposed a new
      technique that involves the direct suturing of common atrioventricular valve
      leaflets to the crest of the ventricular septum. However, we believe that this
      new approach may be associated with left ventricular outflow tract obstruction
      and neomitral valve regurgitation. To avoid these potential complications, we
      decided to modify our repair technique in 2 patients. In this simplified 2-patch
      technique, the operation was done by direct suturing of postero-inferior common
      bridging leaflet to the ventricular crest while the space under the antero
      superior bridging leaflet was closed with a small triangular shaped Dacron patch.
      No echocardiographic evidence of neomitral valve regurgitation and left
      ventricular outflow tract obstruction were detected in either early or late
      postoperative examinations of these patients.

PMID- 12813390
TI  - Relationship between the calibre of carotid arteries and the configuration of the
      circle of Willis in healthy older persons.
AB  - AIM: Recent papers have pointed out that the severity of brain damage that
      follows carotid occlusion is largely influenced by the state of integrity and
      functionality of the circle of Willis. In spite of this, duplex scanning
      investigation of carotid arteries has traditionally been focused on the
      assessment of the degree of the stenosis, while other features, such as the
      calibre of carotid arteries and their possible asymmetry, have often been
      neglected. The aim of the present paper was to verify, in a cohort of older
      persons, whether, based on the calibre of internal carotid arteries and their
      possible asymmetry, abnormalities of the circle of Willis can be predicted. Such
      information could be used to identify high risk patients in whom the status of
      the circle of Willis should be investigated by MR angiography. METHODS: We
      studied 118 healthy older persons with both duplex scanning investigation of
      carotid arteries and MR angiography of the circle of Willis. RESULTS: We found
      that the finding of abnormal internal carotid artery calibres was always
      associated with abnormalities of the precommunicating segments either of the
      anterior or of the posterior cerebral arteries. Abnormalities of communicating
      arteries did not affect the calibre of internal carotid arteries, but
      abnormalities of anterior communicating arteries could always be detected by
      contralateral common carotid artery compression manoeuvres. CONCLUSION: In
      conclusion our findings show that, in healthy older persons, duplex scanning
      investigation of carotid arteries may provide useful information about the
      integrity and functionality of the circle of Willis. Future studies should
      confirm our findings in patients with atherosclerotic lesions of internal carotid
      arteries.

PMID- 12813391
TI  - Cytokine expression in circulating T lymphocytes from patients undergoing carotid
      endarterectomy.
AB  - AIM: We investigated a possible relationship of cytokine expression and phenotype
      features of circulating T lymphocytes with the histological type of
      atherosclerotic plaque removed during carotid endarterectomy. METHODS: Peripheral
      blood samples were taken from 20 patients with carotid atherosclerosis and from 8
      healthy blood donors. Patients were divided into 2 groups according to the
      histological type of their atherosclerotic plaques (types V and VI). Expression
      of intracellular tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma,
      interleukin-4 (IL-4), and of surface antigens (CD4, CD8, CD45RA, CD45RO, T cell
      receptor (TCR) alpha/beta, TCR gamma/delta) in circulating T lymphocytes was
      determined by 3-colour cytofluorimetric analysis. RESULTS: The percentage of T
      lymphocytes primed for TNF-alpha, IFN-gamma and IL-4 was higher in blood samples
      from patients than from healthy subjects; the difference was statistically
      significant for TNF-alpha-producing cells (p=0.01). In patients, the percentage
      of TNF-alpha-producing cells was significantly higher in the CD4+ subset than in
      the CD8+ subset (p=10(-4)). The percentage of TNF-alpha-, IFN-gamma- and IL-4
      primed cells was higher in patients with type VI plaques (complicated lesions)
      than in patients with type V plaques (less complicated lesions). The difference
      was statistically significant for TNF-alpha-primed cells (p=0.05). No
      statistically significant differences were found in T cell phenotype features
      among patients or between patients and healthy subjects. CONCLUSION: Our results
      suggest a relationship between the percentage of circulating T lymphocytes
      expressing TNF-alpha and possibly IFN-gamma and IL-4 and the histological type of
      atherosclerotic plaque in patients with carotid artery disease.

PMID- 12813392
TI  - Progress in the treatment of aneurysms of the distal aortic arch: approach
      through median sternotomy.
AB  - AIM: A review of past and current operative procedures for the treatment of
      aneurysms of the distal aortic arch is presented in conjunction with a series of
      43 patients. In this study, distal aortic arch aneurysm refers to an aneurysm
      involving at least the origin of the left subclavian artery, but not extending
      beyond the left common carotid artery. We excluded dissection aneurysm and
      extended aneurysm to the descending thoracic aorta from this study. METHODS:
      Between January, 1985, and March, 2000, 43 consecutive patients (37 males, 6
      females; mean age 67.5 years) underwent repair of aneurysms of the distal aortic
      arch. The approach to the aneurysm was through a left thoracotomy in 4 patients
      and a median sternotomy in 39 patients, including an additional left thoracotomy
      continued to a median sternotomy in 2 patients. The supportive methods during
      surgery were left heart bypass using a centrifugal pump in 4 patients (LHB
      group), cardiopulmonary bypass with selective cerebral perfusion in 11 patients
      (SCP group), and cardiopulmonary bypass with continuous retrograde cerebral
      perfusion in 28 patients (RCP group). In the RCP group, the "aortic no-touch
      technique" was applied in 21 patients. The operative methods were patch closure
      in 4 patients, graft replacement of the distal arch using the inclusion technique
      in 14 patients, and total arch replacement using the exclusion technique in 25
      patients. RESULTS: There were 5 hospital deaths: 1 patient in the LHB group,
      intractable bleeding; 1 patient in the SCP group, rupture of the distal
      anastomosis; 3 patients in the RCP group, stroke, rupture of the dissection
      arising from the distal anastomosis, and perioperative myocardial infarction.
      Stroke occurred in 1 patient (25%) with LHB, 3 patients (27.2%) with SCP, and 1
      patient (3.6%) with RCP. Among the postoperative survivors, a new onset of left
      recurrent nerve palsy occurred in 2 patients (66.7%) with LHB, 1 patient (10%)
      with SCP, and in 1 patient (4%) with RCP. No neurological injury or left
      recurrent nerve palsy occurred in the patients who underwent the "aortic no-touch
      technique". CONCLUSION: Total arch replacement with the graft exclusion technique
      under profound hypothermic circulatory arrest using RCP through the median
      sternotomy is a promising surgical treatment for atherosclerotic distal aortic
      arch aneurysm. The "aortic no-touch technique" further improved the surgical
      results of the distal aortic arch aneurysm.

PMID- 12813393
TI  - Chronic venous ulcer treatment with fascial pedunculated graft.
AB  - AIM: Chronic venous ulcer treatment is often time consuming and requires a high
      degree of compliance from the patient. This derives not only from venous
      hypertension but also from chronic structural and metabolic changes of underlying
      tissues which impair the healing process. It therefore becomes necessary to
      improve the ulcer tissue condition in order to accelerate the healing process.
      This is obtained mainly with the improvement of local haemodynamics and secondly
      by direct action on the ulcer. The aim of the study is to evaluate the efficacy
      of a treatment with a pedunculated flap of fascia as an additional treatment of
      chronic venous ulcer. METHODS: Four patients classified C6 according to the CEAP
      classification were treated for chronic venous ulcer with correction of venous
      hypertension (saphenectomy or ligature of incompetent perforating veins). The
      patients also underwent rotation of a fascial pedunculated flap transferred from
      the sural area to the perimalleolar area. After 7-15 days they had a free skin
      graft in the treated area. RESULTS: All patients were discharged on the 3(rd)
      postoperative day after the flap rotation. In 3 patients the ulcer healed within
      30 days and in a 4(th) patient within 45 days. No recurrence was observed.
      CONCLUSION: With this method the healing time seems to be shortened compared to
      the typical evolution in patients treated with only reflux control followed by
      conservative therapy. Associating fascial flap in the treatment of chronic venous
      ulcers improves the bed on which the free skin graft is applied. We can also
      hypothesize that this procedure restores the aponeurotic barrier between deep
      venous circulation and superficial microcirculation with the ensuing improvement
      in local venous hypertension.

PMID- 12813394
TI  - Cystic adventitial disease of the popliteal artery. Report of 1 case and review
      of the literature.
AB  - Cystic adventitial disease (CAD) of the popliteal artery is a rare but well-known
      cause of intermittent claudication, especially in young patients. The etiology of
      the disease is still controversial and the literature reports various hypotheses
      for its origin. Diagnosis starts with thorough history taking and physical
      examination; non invasive diagnostic studies comprise color duplex scanner (ECD),
      computed tomography (CT), better if elicoidal (3D CT) and magnetic resonance
      imaging (MRI), which can aid in establishing correct recognition of the disease
      in most cases. A 48-year-old man presented with intermittent right calf
      claudication that had begun 4 months earlier; the symptom-free interval was about
      100 m. MRI and MR angiography of right popliteal fossa revealed the presence of
      an oval cystic (maximum diameter 45 mm). The caudal aspect of the cyst showed
      pedicles protruding between the popliteal vein and the popliteal artery that
      compressed the artery, causing complete occlusion of its lumen. Surgery was
      performed through the posterior approach using an S-shaped incision; the affected
      segment of the popliteal artery was successfully excised and replaced with an
      autogenous external saphenous vein graft. A follow-up is underway, both clinical
      and with; no cyst recurrence has so far been detected either clinically or by
      duplex scanner during the 15-month postoperative follow-up period; the graft is
      patent and the patient is completely symptom free. Severe claudication in young
      patients, possibly without significant vascular risk factors, should prompt the
      clinical suspicion of adventitial cystic disease of the popliteal artery. Medical
      history, clinical examination and non invasive instrumental investigations, such
      as duplex scanner, elicoidal CT and/or MRI, may aid in establishing the correct
      diagnosis.

PMID- 12813395
TI  - Endovascular exclusion of iatrogenic femoral artery pseudoaneurysm with the
      Wallgraft-Endoprosthesis.
AB  - Development of femoral artery pseudoaneurysm represents a continuing problem
      after percutaneous peripheral interventional procedures as well as coronary
      angioplasty. We report a case of symptomatic, expanding femoral artery
      pseudoaneurysm in a 60-year-old man who underwent percutaneous transluminal
      coronary angioplasty and stenting for acute myocardial infarction. A self
      expanding Wallgraft Endoprosthesis (Boston Scientific, USA) was delivered under
      fluoroscopic guidance via contralateral percutaneous femoral approach to the
      site, resulting in immediate complete exclusion of the pseudoaneurysms. Follow-up
      color duplex scanning confirmed false aneurysm exclusion 1 year postprocedure.
      Endovascular treatment of iatrogenic pseudoaneurysm appears to be an attractive
      alternative to surgical repair in critically ill patients, with a high degree of
      technical success, low morbidity and short hospital stay.

PMID- 12813396
TI  - Sigmoid colon exteriorization after ruptured abdominal aortic aneurysm.
AB  - A 74-year-old man in shock was transferred to our hospital. A ruptured abdominal
      aortic aneurysm was diagnosed by computed tomography and an emergency operation
      was thereafter performed. At operation, a massive hematoma was encountered in the
      retroperitoneal space and a standard aneurysmectomy with bifurcated graft
      replacement was carried out. At the end of the operation, signs of sigmoid
      colonic ischemia were recognized, including mild discoloration and bowel spasm.
      After considering the recovery or deterioration from colonic ischemia, we chose
      to exteriorize the sigmoid colon. On the 4th postoperative day, patchy ischemic
      areas of an elevated sigmoid colon were noticed to worsen and as a result, we
      were forced to perform a sigmoid colectomy with end colostomy. Thereafter, the
      patient developed multisystem organ failure, but he recovered gradually. The
      patient was discharged from the hospital 3 months after the initial operation. As
      a complication after surgery for abdominal aortic aneurysms, colonic ischemia
      remains a serious problem, especially in cases of ruptured AAA. It is generally
      better to avoid an operation for both abdominal aortic aneurysms and a colon
      resection at the same time. In this case, an exteriorization of the sigmoid colon
      was selected for the 1st operation in order to treat a ruptured abdominal aortic
      aneurysm. This surgical modality was found to be useful for making a correct
      diagnosis of colonic ischemia before the perforation, while a 2nd look operation
      for colonic ischemia could thus be performed under conditions of a reduced risk
      of infection to the prosthetic graft. These operative procedures were considered
      to be important factors in saving the patient's life.

PMID- 12813397
TI  - Aortic ruptured following lung resection in invasive aspergillosis.
AB  - Invasive pulmonary aspergillosis, although rare in the general population, can
      prove to be an important cause of morbidity and mortality in immunosuppressed
      patients. In this paper we represent a case of aortic rupture for a fungal
      invasion of the aorta after a pulmonary resection procedure. Although a few cases
      are documented in the literature, we report our experience to make our colleagues
      aware of this complication.

PMID- 12813398
TI  - Thyroid abscess associated with a substernal goiter. Case report.
AB  - An abscess associated with an intrathoracic goiter is an extremely rare
      condition. The authors report a case of a thyroid abscess complicated by acute
      dyspnea and asphyxia in a patient of geriatric age with a substernal goiter.
      Surgical therapy was necessary to obtain a correct diagnosis and an effective
      treatment.

PMID- 12813399
TI  - Intrathoracic migration of a humeral orthopedic pin.
AB  - Intrathoracic migration of orthopedic fixation pins occurs infrequently but can
      have dire consequences if not recognized. Described herein is the case of an
      orthopedic pin that migrated from the proximal humerus into lung parenchyma.
      After preoperative computed tomography and fluoroscopy, the pin was removed via
      thoracotomy.

PMID- 12813400
TI  - About ascending aortic dilatation during aortic valve replacement.

PMID- 12813401
TI  - A simple technique to maximize internal thoracic artery length.

PMID- 12813402
TI  - Sudden death in mitral valve prolapse and severe mitral regurgitation. Is chordal
      rupture an indication to early surgery?

PMID- 12813403
TI  - Limitations and pitfalls in separate replacement of the aortic valve and
      ascending aorta: aneurysmal changes in the retained aortic root.

PMID- 12813404
TI  - An intracavitary aspergilloma after echinococcal cystectomy.

PMID- 12813405
TI  - A case report of a pleural synovial sarcoma misdiagnosed as cyst hydatidosis.

PMID- 12813406
TI  - Gastrothoracic wall fistula due to a stab wound. A very rare case report.

PMID- 12813407
TI  - Loss of heterozygosity in patients with pseudoexfoliation syndrome.
AB  - PURPOSE: The purpose of the study was to evaluate the possible occurrence of loss
      of heterozygosity (LOH) in the anterior capsule, lens nucleus, iris, and
      trabeculum samples taken from patients with pseudoexfoliation syndrome (PEX).
      Loss of heterozygosity in a microsatellite marker locus indicates that the
      neighboring gene may be inactivated. Previous attempts to find a gene defect that
      might be responsible for pseudoexfoliation glaucoma have been unsuccessful.
      METHODS: Specimens of the anterior capsule, the lens nucleus, the iris, the
      trabeculum, and reference blood samples were collected from 19 PEX patients.
      Fluorescent multiplex PCR was used to amplify the microsatellite markers located
      on chromosomes 2, 4, 7, 12, 18, 19, and 21. RESULTS: LOH was found in 58% of the
      iris specimens and 50% of the anterior capsule specimens collected from PEX
      patients. The highest incidence of LOH was observed at the marker D7S820.
      CONCLUSIONS: It is possible, that genetic factors may be involved in the etiology
      and pathogenesis of PEX.

PMID- 12813408
TI  - Cells of the human optic nerve head express glial cell line-derived neurotrophic
      factor (GDNF) and the GDNF receptor complex.
AB  - PURPOSE: Glial cell-line derived neurotrophic factor (GDNF) is a distant member
      of the TGFbeta family of growth factors and has wide ranging effects within the
      central nervous system. In the present study we profile the expression of GDNF
      and its receptor complex (Ret and GFRalpha-1) in cells isolated from the human
      optic nerve head (ONH). METHODS: Lamina cribrosa (LC) cells and ONH astrocytes
      were used from normal donors of various ages. Total RNA was isolated and
      subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) to examine
      mRNA expression of GDNF, Ret, and GFRalpha-1. Western immunoblotting and
      immunohistochemistry was used to study protein expression of GDNF and GDNF
      receptor complex proteins in cultured ONH cells. An immunoassay system (ELISA)
      was used to examine secretion of GDNF by ONH cells. Cell proliferation was
      examined following exogenous administration of GDNF. RESULTS: Lamina cribrosa
      cells, ONH astrocytes, and LC tissues expressed messenger RNA for GDNF, Ret and
      GFRalpha-1. Lamina cribrosa cells and ONH astrocytes also expressed protein for
      GDNF, Ret, and GFRalpha-1. Secretion of GDNF by either cell type was not
      detected. Exogenous GDNF caused a significant increase in cell proliferation of
      LC cells but not ONH astrocytes. CONCLUSIONS: Cells from the human lamina
      cribrosa express mRNA and protein for GDNF and its receptor complex. LC cells
      proliferate in response to exogenous GDNF. The potential for autocrine and/or
      paracrine GDNF signaling thus exists within the lamina cribrosa, a tissue
      involved in glaucoma pathogenesis.

PMID- 12813409
TI  - Inhibition of plasminogen activation protects against ganglion cell loss in a
      mouse model of retinal damage.
AB  - PURPOSE: The mechanisms that trigger ganglion cell death in ischemic retinal
      diseases are not clearly understood. Using a mouse optic nerve ligation model,
      the objective of this study was to test the hypothesis that extracellular matrix
      (ECM) modulating plasminogen activators (PAs) potentiate ganglion cell loss.
      METHODS: Optic nerve ligation was performed to initiate ganglion cell loss in the
      retina. Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen
      activator (tPA) activity in retinal extracts was determined by
      plasminogen/fibrinogen zymography. Immunostaining and western blot analysis was
      performed to detect uPA and tPA proteins. Plasmin activity was determined by
      casein gel-zymography. Plasminogen and plasmin proteins were detected and
      quantified by western blotting. Morphology was assessed using hematoxylin and
      eosin stained retinal cross sections, and programmed cell death was monitored by
      an apoptotic assay. Laminin degradation in retinal extracts was assessed by
      western blot analysis. RESULTS: Optic nerve ligation led to a transient increase
      in uPA and plasmin proteolytic activity in the retina. Urokinase inhibitor,
      amiloride, blocked uPA activity in retinal extracts. We found a correlation
      between the increased uPA activity, and conversion of zymogen plasminogen to
      active plasmin in retinal extracts with laminin degradation in the retina and
      apoptosis of ganglion cells. We found that by adding exogenous plasmin, in vitro,
      laminin present in control retinal extracts could be degraded in similar fashion.
      In addition, uPA or tPA failed to degrade laminin in control retinal extracts
      unless plasminogen was added, indicating that plasminogen activation is necessary
      for laminin degradation, in vitro. After intravitreal injection of plasmin
      inhibitor, alpha-2 antiplasmin, we found a significant protection against optic
      nerve ligation-induced ganglion cell loss. CONCLUSIONS: Optic nerve ligation
      induced plasmin(ogen) activation that precedes ganglion cell loss suggest that
      specific targeting of plasmin activity may have therapeutic potential in
      preventing ganglion cell loss in retinal diseases.

PMID- 12813411
TI  - Nurses' knowledge regarding patients with intravenous catheters and phlebitis
      interventions.
AB  - This study was planned and applied in 2 stages. Stage I was applied to determine
      the knowledge of nurses working in the internal medicine, surgery, obstetrics and
      gynecology, pediatrics, and other services in Celal Bayar University Hospital
      about using intravenous catheter and intravenous fluid treatment, and the
      symptoms and treatment procedure for phlebitis. Stage II consisted of observation
      of all patients who had intravenous catheters for symptoms of phlebitis for 5
      days and the interventions the nurses used for the patients who had phlebitis. In
      stage I, questionnaires were used to determine the knowledge of the nurses; in
      stage II, 2 investigators observed the patients. Results were evaluated using
      SPSS software with chi(2) statistical analysis. Nurses were found to have high
      knowledge levels, but their practices were not suitable to their knowledge
      levels. Of the patients who participated in the study, 67.24% showed symptoms of
      phlebitis. We found that there was a significant relationship (P <.05) between
      the selection of the vein and the occurrence of phlebitis in patients who had an
      intravenous catheter. We also found that the relationships between the age groups
      of the patients and phlebitis and the relationships between the diagnosis and
      phlebitis were statistically significant (P <.05).

PMID- 12813413
TI  - Development of evidence-based protocols for evaluation and management of
      dysfunctional vascular access devices in interventional radiology.
AB  - Assessment and treatment of dysfunctional vascular access devices (VADs) is a
      mutual responsibility of nurses who use these devices and the interventional
      radiology (IR) team. Understanding causes of dysfunction, implementing assessment
      and treatment protocols, and communication between referral areas and the IR team
      are beneficial to both areas and to the patient. This study describes development
      of evidence-based protocols, combining research utilization and a quality
      improvement educational process.

PMID- 12813414
TI  - Management of hyperlipidemia in patients with vascular disease.
AB  - Atherosclerosis contributing to cardiovascular disease is the leading cause of
      death in the United States. It is also the major cause of peripheral arterial
      disease (PAD). Although there is substantial evidence that aggressive treatment
      of hyperlipidemia improves the outcome of patients with coronary artery disease
      (CAD), relatively little attention has been directed toward lipid control in
      patients with PAD. The National Cholesterol Education Program (NCEP) has
      established guidelines for treatment of lipids in patients with atherosclerotic
      disease. The purpose of this study was to determine the effectiveness of current
      lipid management practices in patients electively admitted for peripheral
      vascular surgery and to explore methods to improve compliance with NCEP
      guidelines. The past medical/surgical history, risk factors for atherosclerosis,
      and medication regimen including lipid medications were obtained from a
      retrospective review of the medical records of 105 consecutive patients scheduled
      for an elective vascular procedure. Lipid profiles were obtained as part of their
      routine preoperative assessment and the results were compiled and compared with
      established NCEP guidelines to determine the level of compliance in our PAD
      population. Eighty-five of the 105 patients had lipid profiles recorded in the
      medical record. Only 42% of patients were at or below the recommended goal of
      less than 100 mg/dL for low-density lipoprotein (LDL). Greater than half of
      patients had previous diagnosis of atherosclerosis or had previous bypass
      including coronary artery bypass surgery. Despite the strong emphasis on lipid
      reduction, especially LDL cholesterol, only a minority of patients admitted for
      peripheral vascular surgery were at the recommended NCEP goal. More aggressive
      evaluation and treatment of lipid disorders in patients with PAD seems warranted.

PMID- 12813416
TI  - Case report: Blue toe syndrome caused by a true crural aneurysm.

PMID- 12813417
TI  - Hyperperfusion syndrome after carotid endarterectomy.

PMID- 12813418
TI  - Iliofemoral deep vein thrombosis.

PMID- 12813423
TI  - Ethical issues in surgical treatment and research.

PMID- 12813424
TI  - Making our world a good place to grow old.

PMID- 12813425
TI  - Diabetes-associated bladder dysfunction in the older adult (CE).
AB  - Diabetic cystopathy is a chronic complication of diabetes with a classic triad of
      symptoms: decreased bladder sensation, increased bladder capacity, and impaired
      detrusor contractility. This article discusses age- and diabetes-related changes
      that affect lower urinary tract function. The article also reviews bladder
      function in the older adult diabetic, explores bladder dysfunction prevention,
      and suggests management strategies for diabetic cystopathy. Little research has
      been published to date to guide practice in this area, and opportunities exist
      for nursing research to fill the gap in knowledge.

PMID- 12813427
TI  - What evidence underlies our practice with alzheimer families?
AB  - Registered nurses who base their practice on scientific evidence can justify
      their decisions and the care they provide to the families of people with
      Alzheimer disease (AD). The health care literature should provide an evidence
      base for nurses to draw on. Families care for older members with AD, regardless
      of whether the setting is a family home, long-term care facility, or day-support
      program. Sometimes families say they need information to enable them to provide
      quality care. Their questions may include "What happens next?" "Where do we go
      from here?" or "How do I stop the wandering?" This study reviewed AD education
      articles in five journals used by gerontologic health care workers-primarily
      registered nurses. Findings identified a serious lack of education-specific
      articles. The implication is whether registered nurses are meeting the education
      needs of families.

PMID- 12813428
TI  - Geriatric alcohol abuse: a national epidemic.
AB  - Substance abuse is a widely identified problem in our society. Alcohol abuse is
      the most problematic, yet most undertreated. Primary care practitioners often do
      not screen the geriatric population appropriately for at-risk drinking, so the
      condition goes undiagnosed. This oversight is complicated by the fact that many
      manifestations of alcohol abuse do not present themselves until well into the
      disease process. This article explores the practitioner's role in geriatric
      alcohol abuse assessment and treatment and the impact of geriatric alcohol abuse
      on society.

PMID- 12813429
TI  - Moderate alcohol consumption and unappreciated risk for alcohol-related harm
      among ethnically diverse, urban-dwelling elders.
AB  - The purpose of this cross-sectional survey was to gather data describing how
      older adults define moderate alcohol consumption and how they have interpreted
      media reports of the health benefits of moderate alcohol consumption. Results
      showed that many older adults define moderate alcohol use at levels above Federal
      guidelines, and a notable number of older adults agree that moderate use is good
      for health. The disparity between older adults' definition of moderate drinking
      and Federal guidelines for low-risk drinking may contribute to the
      underrecognition of problem drinking by nurses and other health care providers
      and place older adults at an unappreciated level of risk for alcohol-related
      harm.

PMID- 12813430
TI  - Aging memory self-efficacy: elders share their thoughts and experience.
AB  - Twenty-six elders responded to an open-ended question as part of a study that
      examined the relationships among depression, health, memory self-efficacy, and
      metamemory. Participants rated their overall memory function as fair to average
      (M = 4.26, standard deviation [SD] = 1.29). The average memory efficacy scores
      were high (M = 51.35, SD = 23.56). The final question invited participants to
      share any additional information they thought might be important to this item.
      This article represents a content analysis of these comments. The mean age of
      responders was 68.78; all had high perceived health and no depression. No
      differences on memory self-efficacy arose among age groups. Themes included
      memory management, rationalization, reflection, information seeking, and
      correlation establishment. Therefore, it is important for clinicians to ask
      elders about memory function during routine health care encounters, as
      individuals are interested in memory assessment and management.

PMID- 12813431
TI  - Empowering nursing staff and residents in long-term care.
AB  - An exploration of empowering and disempowering experiences among nursing staff
      members and long-term care residents yielded themes based on educational,
      communication, and relationship needs of nursing staff and environmental and
      relationship needs of residents in long-term care. Strategies for empowering
      nursing staff and residents are suggested.

PMID- 12813433
TI  - Teaching communication skills to nursing home certified nursing assistants.
AB  - Increasing numbers of terminally ill patients are admitted to nursing homes.
      Quality palliative care requires good communication skills, but certified nursing
      assistants (CNAs), who spend the most time with residents, are inadequately
      trained. They receive little education in communication during training programs
      or as in-services in the nursing home. Education and role-playing during their
      training program could be used to learn these skills, as could a series of short
      videos. Further research is needed to develop and test new methods of teaching
      communication skills to nursing home CNAs.

PMID- 12813438
TI  - Geriatric nurse practitioner care guidelines: depression in older adults.

PMID- 12813440
TI  - Did I help my patient choose death?

PMID- 12813441
TI  - So what's a woman to do about menopause?

PMID- 12813442
TI  - Probiotics and prebiotics for bowel health.

PMID- 12813443
TI  - Host conditioning with total lymphoid irradiation and antithymocyte globulin
      prevents graft-versus-host disease: the role of CD1-reactive natural killer T
      cells.
AB  - Our previous studies in mice showed that the nonmyeloablative conditioning
      regimen of fractionated irradiation of the lymphoid tissues (total lymphoid
      irradiation; TLI) and depletive anti-T-cell antibodies (anti-thymocyte serum)
      markedly increased the percentage of regulatory DX5+ and natural killer 1.1+ T
      cells in the mouse spleen, and prevented acute lethal graft-versus-host disease
      (GVHD) in BALB/c mice (H-2(d)) following the transplantation of bone marrow (BM)
      and peripheral blood mononuclear cells (PBMC) from C57BL/6 (H-2(b)) donors. The
      object of the current study was to determine whether the TLI and anti-thymocyte
      serum regimen protected natural killer T-cell deficient CD1(-/-) BALB/c mice
      against GVHD after BM and PBMC transplantation from C57BL/6 donors, and whether a
      similar conditioning regimen of TLI and anti-thymocyte globulin (ATG) can prevent
      GVHD in Lewis rat (RT1(l)) hosts after BM and PBMC transplantation from ACI rat
      (RT1(a)) donors. The experimental results in mice showed that, although wild-type
      BALB/c hosts are protected in association with a marked increase in CD1- reactive
      T cells expressing the invariant TCR identified with a CD1 tetramer reagent; CD1(
      /-) BALB/c hosts are not. Studies of chimeric donor cells in mice protected from
      GVHD showed donor T-cell polarization to a Th2 cytokine pattern. Results in rats
      showed that approximately 1000 fold more donor PBMC cells were required to induce
      a similar incidence of lethal GVHD in TLI and ATG conditioned hosts as compared
      with hosts conditioned with single-dose total-body irradiation or total-body
      irradiation and ATG. Surviving TLI and ATG conditioned rat hosts were complete
      chimeras. In conclusion, the TLI and ATG/anti-thymocyte serum conditioning
      regimen protects against GVHD in rats and mice, and regulatory natural killer T
      cells are required for protection.

PMID- 12813444
TI  - Bone marrow purging studies in acute myelogenous leukemia using the recombinant
      anti-CD33 immunotoxin HuM195/rGel.
AB  - This study was designed to determine the effect of immunotoxin HuM195/rGel on
      normal human bone marrow before clinical purging. HuM195/rGel is composed of the
      recombinant plant toxin gelonin (rGel) chemically coupled to the anti-CD33 human
      chimeric antibody HuM195. The CD33 antigen is of significant interest as a target
      for therapy of acute myelogenous leukemia because it is present in leukemic
      blasts of most patients but absent in the earliest progenitor bone marrow cells.
      HuM195/rGel was optimally cytotoxic to acute myelogenous leukemia HL60 cells with
      24 hours of exposure. We developed an in vivo purging model by mixing mobilized
      peripheral blood progenitor cells with HL60 cells to simulate a remission in bone
      marrow. Cells were treated with 10 nmol/L of HuM195/rGel either with or without
      exposure to freeze/thaw procedure, which has been reported to act synergistically
      with HuM195/rGel to produce cytotoxic effect. When clonogenic cell recovery rates
      were determined, HuM195/rGel alone did not affect normal peripheral blood
      progenitor cells, whereas HuM195/rGel plus freeze/thaw provided 2 logs of tumor
      cell elimination in our purging model. We also observed similar results under
      conditions used in the transplantation setting. We concluded that for acute
      myelogenous leukemia blasts expressing CD33, HuM195/rGel could be useful as a
      purging reagent for autologous transplantation.

PMID- 12813445
TI  - Nonmyeloablative bone marrow transplantation: Infectious complications in 65
      recipients of HLA-identical and mismatched transplants.
AB  - Infections are a common complication of allogeneic bone marrow transplantation
      and the leading cause of transplantation-related mortality. It had been
      hypothesized that transplantation following nonmyeloablative preparative regimens
      would result in fewer infections by causing less mucosal injury, less graft
      versus-host disease, and allowing earlier immune reconstitution. We have
      retrospectively reviewed the infectious complications of 65 consecutive patients
      with advanced hematologic malignancies who underwent bone marrow transplantation
      using a novel preparative regimen consisting of cyclophosphamide, thymic
      irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection
      occurred in 52% of cases in which the donor or recipient had evidence of prior
      CMV exposure. Using a strategy of preemptive therapy and secondary prophylaxis
      with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria
      predominated over the first 100 days after bone marrow transplantation.
      Thereafter, the relative proportion of gram-negative infections increased without
      a significant increase in episodes of neutropenia. The rate of bacterial
      infections was not influenced by relapse of the underlying malignancy. Seven
      patients developed infections with Aspergillus species, which was the most common
      infectious cause of death in these patients. Infections with viruses other than
      CMV (n=10) and with protozoan organisms (n=2) also occurred. The use of HLA
      mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease,
      and treatment with corticosteroids did not influence the risk of CMV or bacterial
      or fungal infections in patients who underwent transplantation following this
      preparative regimen. Overall, the incidence and spectrum of infections in this
      series was similar to the reported incidence of infections following conventional
      myeloablative allogeneic stem cell transplantation. We conclude that a
      quantitative T-cell deficiency in these extensively T-cell depleted patients may
      be a risk factor for infection, even in the absence of graft-versus-host disease.

PMID- 12813446
TI  - High-dose myeloablative therapy and autologous peripheral blood progenitor cell
      transplantation for elderly patients (greater than 65 years of age) with relapsed
      large cell lymphoma.
AB  - Eleven elderly patients (older than 65 years) with relapsed large cell lymphoma
      were treated with high-dose myeloablative therapy and autologous peripheral blood
      progenitor cell support (ABMT). All 11 patients were in sensitive relapse at the
      time of ABMT. Treatment-related mortality was 9%. Median CD34 cell collection was
      4.8 x 10(6) cells/kg. Median time to hematologic recovery was 11 days for
      granulocytes (range, 9 to 16 days) and 18 days for platelets (range, 14 to 42
      days). Nine of 11 patients (81%) achieved a complete response following ABMT.
      Median time to treatment failure was 17 months. The 4-year disease-free and
      overall survival is projected to be 44%. When compared with a cohort of patients
      under age 65 years with sensitive relapsed large cell lymphoma treated with ABMT
      during the same time interval, disease-free and overall survival are comparable.
      ABMT is feasible, tolerable, and effective in elderly patients with relapsed
      large cell lymphoma with disease-free survival rates comparable to younger
      patients.

PMID- 12813447
TI  - Optimistic expectations and survival after hematopoietic stem cell
      transplantation.
AB  - An optimistic attitude is hypothesized to be beneficial when facing a life
      threatening medical condition. However, the actual relationship of high
      expectations for treatment success and medical outcome is controversial. Using a
      prospective cohort of 313 autologous and allogeneic hematopoietic stem cell
      transplant patients enrolled July 1996 through November 1999, we tested whether
      patient-reported expectations before transplantation were associated with
      survival and quality of life following the procedure. Before transplantation,
      patients with higher expectations that the transplant procedure would go well had
      better mental and emotional functioning, but similar physical status and medical
      condition to patients with less optimistic expectations. In the first 2 months
      after transplantation, optimistic expectations were associated with better
      survival (92% v 84%; relative risk for mortality 0.45, 95% confidence interval
      0.22-0.92; P=.03) controlling for other physical and mental characteristics.
      However, by 6 months posttransplantation, survival and quality of life were
      indistinguishable between patients with initially higher and lower expectations.
      Our data suggest an association between more optimistic expectations and early
      survival following hematopoietic stem cell transplantation, but this association
      is not present by 6 months posttransplantation.

PMID- 12813448
TI  - Primary amyloidosis patients with significant organ dysfunction tolerate
      autologous transplantation after conditioning with single-dose total body
      irradiation alone: a feasibility study.
AB  - High-dose melphalan has been commonly used as conditioning for amyloidosis with
      considerable toxicity. We hypothesized that the novel conditioning regimen of 550
      cGy total body irradiation (TBI) alone for autologous peripheral blood stem cell
      transplantation would have reduced organ toxicity and thus permit safer
      transplantation of primary amyloidosis patients, even those with poor risk
      disease. The comprehensive regimen included pretransplantation chemotherapy,
      single-dose TBI alone (550 cGy at 30 cGy/min) conditioning, and post
      transplantation interferon-alpha maintenance. Thirteen patients were enrolled in
      this feasibility study. Patients with multiorgan involvement were included; 10
      patients had poor or intermediate risk disease. Cardiac toxicity was significant.
      Treatment-related mortality through 100 days post-transplantation was 15% and was
      caused by cardiac mortality. One patient died from arrhythmia after receiving
      TBI; 2 patients had grade IV cardiac toxicity (with subsequent complete
      recovery). One patient died 1 month after mobilization from progressive
      cardiomyopathy and never received conditioning. However, noncardiac organ
      toxicity was mild. No patient required parenteral nutrition support; no patient
      developed mucositis; and no patient experienced gastrointestinal bleeding
      following transplantation. The complete hematologic remission rate was 45%, with
      pretransplantation chemotherapy being the most active part of the regimen.
      Survival estimates from enrollment to 1 and 2 years post-transplantation were 66%
      and 47%, respectively. Causes of death were disease progression (6),
      myelodysplasia (1), arrhythmia following TBI (1), and congestive heart failure
      after mobilization (1). In this cohort of primary amyloidosis patients, the
      transplantation regimen of 550 cGy TBI was feasible and associated with modest
      treatment-related mortality. Efficacy with TBI conditioning may be reduced
      compared with high-dose melphalan, but this should be explored in a future trial
      with a larger cohort of patients.

PMID- 12813449
TI  - Recombinant human thrombopoietin augments mobilization of peripheral blood
      progenitor cells for autologous transplantation.
AB  - This study assessed the ability of various schedules of recombinant human
      thrombopoietin (rhTPO) to enhance mobilization of peripheral blood progenitor
      cells (PBPCs) in 134 patients with cancer undergoing high-dose chemotherapy and
      autologous PBPC transplantation. Patients received the study drug on days 1, 3,
      and 5 before initiation of granulocyte colony-stimulating factor (G-CSF) 10
      microg/kg/day on day 5 and pheresis starting on day 9. Randomly assigned
      treatments on days 1, 3, and 5 were: group 1 (n=27) placebo, placebo, rhTPO 1.5
      microg/kg; group 2 (n=27) rhTPO 1.5 microg/kg, placebo, placebo; groups 3 (n=28)
      and 4 (n=22) rhTPO 0.5 microg/kg on all 3 treatment days; and group 5 (n=30)
      placebo on all 3 treatment days. After high-dose chemotherapy and PBPC
      transplantation, groups 1 through 4 received rhTPO 1.5 microg/kg days 0, +2, +4,
      and +6 with either G-CSF 5 microg/kg/day (groups 1-3) or granulocyte-macrophage
      colony-stimulating factor 250 microg/m(2)/day (group 4). Group 5 received placebo
      plus G-CSF 5 microg/kg/day. The addition of rhTPO to G-CSF increased median CD34+
      cell yield/pheresis in cohorts in which rhTPO was started before day 5, with
      higher yields in groups 2 (2.67 x 10(6)/kg) and groups 3 and 4 (3.10 x 10(6)/kg)
      than in group 1 (1.86 x 10(6)/kg) or group 5 (1.65 x 10(6)/kg) (P=.006 across
      groups). Comparing rhTPO to placebo, higher percentages of patients achieved the
      minimum yield of CD34+ > or =2 x 10(6)/kg (92% v 75%; P=.050) as well as the
      target yield of CD34+ > or =5 x 10(6)/kg (73% v 46%; P= .041). rhTPO-treated
      patients required fewer phereses to achieve minimum (P= .011) and target (P=
      .015) CD34+ cell values. rhTPO given after transplantation did not speed platelet
      recovery. No neutralizing antibodies were observed. We conclude that rhTPO can
      safely enhance mobilization of PBPC, reduce the number of leukapheresis, and
      allow more patients to meet minimal cell yield requirements to receive high-dose
      chemotherapy with PBPC transplantation.

PMID- 12813455
TI  - Gadd34 functional domains involved in growth suppression and apoptosis.
AB  - Gadd34 (also known as MyD116) was originally described as a growth arrest and DNA
      damage-inducible gene. Increased expression of Gadd34 was subsequently found to
      correlate with apoptosis, and forced overexpression of the protein leads to
      apoptosis. Gadd34 protein modulates protein phosphatase type 1 activity through
      both direct binding to the protein, as well as through binding to other proteins
      that also modulate phosphatase activity. In addition, Gadd34 has a region of
      homology with the herpes simplex virus type 1 ICP34.5 protein that is involved in
      the prevention of apoptosis in infected cells. Recently it was reported that a
      novel rat Gadd34-related gene, PEG-3, was upregulated in transformed cells, and
      that forced expression of this gene led to increased tumorigenic potential of
      cells implanted into nude mice and increased angiogenesis of these tumors. We
      have found, however, that PEG-3 does not exist in normal rat cells, which have a
      single diploid complement of Gadd34. Sequence analysis of the rat Gadd34 gene and
      comparison with PEG-3 indicates that PEG-3 is most likely a mutant of Gadd34 that
      perhaps arose as a result of transformation. This finding suggests that truncated
      Gadd34 may interfere with normal Gadd34 function in transfected cells. However,
      human Gadd34 lacking the viral homology domain does not interfere with normal
      Gadd34-induced apoptosis in cultured cells. This suggests that viral similarity
      sequences may be required for Gadd34-mediated functions other than apoptosis.

PMID- 12813456
TI  - Interaction of the HPV E7 proteins with the pCAF acetyltransferase.
AB  - Most cervical carcinomas express the E6 and E7 proteins of a high-risk human
      papillomavirus (HPV). These proteins affect growth control by interfering with
      the functions of cell regulatory proteins, promoting oncogenic transformation. A
      key target of E7 is the tumor suppressor protein pRb, which directly interacts
      with E7. However, binding to additional cellular regulatory proteins is clearly
      required for oncogenesis, as mutants of E7 have been identified that bind to pRb,
      yet fail to transform efficiently. Here we demonstrate the interaction of the HPV
      6, 16 and 18 E7 proteins with the pCAF acetyltransferase, which has been reported
      to function as a coactivator for a variety of transcription factors including
      p53. Mutation of a highly conserved leucine residue within the zinc finger region
      of HPV 16 E7 disrupts binding to pCAF and also impairs transformation and
      transcriptional activation. HPV 16 E7 interacts with the acetyltransferase domain
      of pCAF, and reduces its acetyltransferase activity in vitro. Our analysis of the
      interaction between the pCAF acetyltransferase and E7 provides new insight into
      the mechanisms by which the E7 oncoproteins can alter cellular gene expression
      and growth.

PMID- 12813457
TI  - TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL
      induced apoptosis mediated by NF-kappaB.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent
      inducer of apoptosis in cancer cells. Examining primary cells of children with
      untreated acute leukemia, TRAIL induced apoptosis in 50% of cells, but to our
      surprise attenuated spontaneous apoptosis in the remaining samples or, most
      importantly, even mediated proliferation. We therefore examined tumor cell lines
      of leukemic and nonleukemic origin with apoptosis resistance towards TRAIL
      because of absent Caspase-8 or dysfunctional FADD. In all cell lines tested,
      TRAIL treatment increased cell numbers in average to 163% within 4 days and
      accelerated doubling time from 24 to 19 h. TRAIL-mediated proliferation was
      completely abrogated by blockade of NF-kappaB activation using proteasome
      inhibitors or in RIP-negative, IKKgamma-negative cells or in cells overexpressing
      dominant-negative IkappaBalpha. Our data describe the biological significance of
      TRAIL-mediated activation of NF-kappaB in cancer cells resistant to TRAIL
      mediated apoptosis: TRAIL leads to an increase in tumor cell count by a
      prosurvival and possibly mitogenic function. Given the promising therapeutic
      potential of TRAIL as a novel anticancer drug, TRAIL-mediated survival or
      proliferation of target cells may restrict its use to apoptosis-sensitive tumors.

PMID- 12813458
TI  - Inhibition of histone deacetylase activity increases chromosomal instability by
      the aberrant regulation of mitotic checkpoint activation.
AB  - Histone modification through acetylation and deacetylation is a key process in
      transcription, DNA replication, and chromosome segregation. During mitosis,
      histones are highly acetylated and chromatin is condensed. Here, we investigate
      the mechanistic involvement of histone deacetylase (HDAC) activity in the
      regulation of mitotic checkpoint activation. Inhibition of HDAC activity was
      found to cause the improper kinetochore localization of the mitotic checkpoint
      proteins, and to prolong mitotic arrest, and thus to lead to chromosomal
      instability due to aberrant exit from the mitotic cell cycle arrest. In addition,
      treatment with HDAC inhibitor attenuated the activations of p38 and ERK kinases,
      and increased the expression levels of cIAP-1, suggesting that the observed
      increased adaptation and chromosomal instability induced by inhibiting HDAC
      activity might be directly connected with the activations of cell survival and/or
      antiapoptotic signals. Moreover, the treatment of cells with mitotic defects with
      HDAC inhibitor increased their susceptibility to chromosomal instability. These
      results support the notion that HDAC activity plays an important role in the
      regulation of mitotic checkpoint activation, and thus the aberrant control of
      HDAC activity contributes to chromosomal instability.

PMID- 12813459
TI  - Aneuploidy of human testicular germ cell tumors is associated with amplification
      of centrosomes.
AB  - Testicular germ cell tumors occur in three age groups. Seminomas and nonseminomas
      of adults, including mature teratomas, and the precursor carcinoma in situ (CIS)
      are aneuploid. This also holds true for yolk sac tumors of newborn and infants,
      while the mature teratomas of this age are diploid. In contrast, spermatocytic
      seminomas occurring in the elderly contain both diploid and polyploid cells.
      Aneuploidy has been associated with centrosome aberrations, sometimes related to
      overexpression of STK15. Aneuploidy of non-neoplastic germ cells has been
      demonstrated in the context of male infertility, a risk factor for the
      development of seminoma/nonseminoma. We investigated aneuploidy, centrosome
      aberrations and the role of STK15 in different types of testicular germ cell
      tumors as well as in normal and disturbed spermatogenesis. The aneuploid
      seminomas and nonseminomas tumors (including CIS) showed increased numbers of
      centrosomes, without STK15 amplification or overexpression. Four out of six
      infantile teratomas had normal centrosomes, the remaining two and an infantile
      yolk sac tumor showed a heterogeneous pattern of cells with normal or amplified
      centrosomes. Spermatocytic seminomas had two, four or eight centrosomes. Germ
      cells in seminiferous tubules with disturbed spermatogenesis shared both
      aneuploidy and centrosome abnormalities with seminomas/nonseminomas and showed a
      more intense STK15 staining than those with normal spermatogenesis and CIS.
      Therefore, aneuploidy of testicular germ cell tumors is associated with amplified
      centrosomes probably unrelated to STK15.

PMID- 12813460
TI  - Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an
      arm-like domain to clamp around double-stranded DNA.
AB  - The human tumor suppressor gene ataxia telangiectasia mutated (ATM) encodes a
      3056 amino-acid protein kinase that regulates cell cycle checkpoints. ATM is
      defective in the neurodegenerative and cancer predisposition syndrome ataxia
      telangiectasia. ATM protein kinase is activated by DNA damage and responds by
      phosphorylating downstream effectors involved in cell cycle arrest and DNA
      repair, such as p53, MDM2, CHEK2, BRCA1 and H2AX. ATM is probably a component of,
      or in close proximity to, the double-stranded DNA break-sensing machinery. We
      have observed purified human ATM protein, ATM-DNA and ATM-DNA-avidin bound
      complexes by single-particle electron microscopy and obtained three-dimensional
      reconstructions which show that ATM is composed of two main domains comprising a
      head and an arm. DNA binding to ATM induces a large conformational movement of
      the arm-like domain. Taken together, these three structures suggest that ATM is
      capable of interacting with DNA, using its arm to clamp around the double helix.

PMID- 12813461
TI  - Activation of beta-catenin in prostate epithelium induces hyperplasias and
      squamous transdifferentiation.
AB  - The Wnt/beta-catenin signaling pathway is critical for normal mammalian
      development, the specification of epidermal cells and neoplastic transformation
      of intestinal epithelium. However, precise molecular information regarding cell
      specific responses to beta-catenin signaling has been limited. This question was
      addressed using a mouse model in which exon 3 of the beta-catenin gene was
      deleted in several cell types with loxP-mediated recombination utilizing a Cre
      transgene under control of the mouse mammary tumor virus-long terminal repeat
      (MMTV-LTR). The stabilization of beta-catenin in prostate epithelium resulted in
      hyperplasias and extensive transdifferentiation into epidermal-like structures,
      which expressed keratins 1 and 6, filaggrin, loricrin and involucrin. The cell
      specific loss of NKCC1 protein and reduced nuclear Stat5a is further suggestive
      of a loss of prostate epithelial characteristics. In addition to the prostate,
      hyperplasias and squamous metaplasias were detected in epithelia of the
      epididymis, vas deferens, coagulating gland, preputial gland and salivary gland.
      However, and in contrast to a recent study, no lesions reminiscent of high-grade
      prostate intraepithelial neoplasia were detected. Since beta-catenin was
      activated in several cell types and impinged upon the viability of these mice, it
      was not possible to evaluate the cumulative effect over more than 3 months. To
      assess long-term consequences of beta-catenin activation, mutant and control
      prostate tissues were transplanted into the mammary fat pads of wild-type males.
      Notably, squamous metaplasias, intra-acinous hyperplasia and possible neoplastic
      transformation were observed after a total of 18 weeks of beta-catenin
      stimulation. This suggests that the transdifferentiation into squamous
      metaplasias is an early response of endoderm-derived cells to beta-catenin, and
      that the development of intra-acinous hyperplasias or neoplastic foci is a later
      event.

PMID- 12813462
TI  - Peroxisome proliferator-activated receptor-gamma upregulates caveolin-1 and
      caveolin-2 expression in human carcinoma cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor for eicosanoids that promotes differentiation of human epithelial and
      mesenchymal cells in vitro and in vivo. PPARgamma was proposed as a target for
      drug-induced differentiation therapy of cancer. Caveolin-1 is a constituent of
      plasma membrane caveolae in epithelial cells that is often downregulated upon
      oncogenic transformation. Caveolin-1 has growth-inhibitory activities and its
      disruption is sufficient to induce transformation in fibroblasts. Herein we have
      tested the hypothesis that caveolins are transcriptional target genes for
      PPARgamma. In human HT-29 colon carcinoma cells, thiazolidinedione PPARgamma
      ligands increased the levels of caveolin-1 and caveolin-2 proteins two to
      fivefold in a concentration-dependent manner within 24 h. In human MCF-7 breast
      adenocarcinoma cells, nonthiazolidinedione PPARgamma ligands elevated caveolin-2
      protein three to fourfold, while the thiazoli-dinediones were less effective.
      Caveolin-1 mRNA levels were found to be upregulated by PPARgamma ligands already
      after 3 h in both the cell lines. Ectopic expression of a dominant-negative
      PPARgamma construct attenuated ligand-induced upregulation of caveolins in both
      HT-29 and HEK-293T cells, indicating that ligand action is mediated by PPARgamma.
      Ligand-treated MCF-7 cells exhibited a differentiated phenotype, as evinced by
      analysis of cell-specific differentiation markers: protein levels of maspin were
      elevated and perinuclear lipid droplets accumulated. In contrast, in HT-29 cells,
      caveolin expression was not correlated with differentiation. Interestingly,
      PPARgamma partially cofractionated in lipid rafts and could be
      coimmunoprecipitated from cell lysates with caveolin-1, indicating that PPARgamma
      and caveolin-1 may coexist in a complex. Our data indicate that PPARgamma
      participates in the regulation of caveolin gene expression in human carcinoma
      cells and suggest that caveolin-1 may mediate some of the phenotypic changes
      induced by this nuclear receptor in cancer cells. These findings may have
      potentially important functional implications in the context of cancer
      differentiation therapy and multidrug resistance.

PMID- 12813463
TI  - Transcriptional regulation of the promoter of the rat frizzled related protein
      gene by CREB.
AB  - Frizzled related proteins (Frps) are secreted proteins structurally similar to
      frizzled receptors; they bind Wnt via the cysteine-rich domain and antagonize the
      Wnt signaling pathway. In this study, we have investigated the mechanisms
      regulating the transcriptional regulation of rat Frp (rFrp) promoter. From
      previous findings, we know that the transcriptional activation domain of rFrp
      resides in the region -202 to -144 relative to the transcription start site, and
      that it is essential for efficient promoter activity. The study presented here
      was designed to identify trans-acting factors that bind to this critical domain
      of the rFrp promoter and to elucidate the pathway involved in the regulation of
      rFrp expression. Electrophoretic mobility shift assay (EMSA) demonstrated that
      specific DNA-protein binding activities fall into two adjacent core sequences
      with (CTTTGGGGG) at -197 to -189 and (AGATGATGTAA) at -151 to -141 of the rFrp
      promoter. Reporter assay showed that these core sequences are both required for
      the activation of rFrp promoter. Mutation within either one or both core sequence
      drastically reduced the promoter activity. Southwestern blotting showed that the
      estimated molecular mass of the distinct binding protein to the (AGATGATGTAA)
      domain is about 43 kDa. Further EMSA suggested CREB as the trans-acting factor in
      the DNA-protein complex, which was out competed by CREB consensus
      oligonucleotides and supershifted by anti-CREB antibody. Overexpression of PKA
      and CREB also transactivated rFrp promoter, and dominant-negative CREB inhibited
      the promoter activity in transient reporter assays. More importantly, CREB,
      phosphorylated CREB and the adaptor protein CBP were found binding to the
      endogenous rFrp promoter using chromatin immunoprecipitation assay. Collectively,
      our results demonstrate the induction of rFrp promoter activity by PKA and CREB
      in vitro, and the binding of CREB and CBP to the rFrp promoter core motif in
      vivo.

PMID- 12813464
TI  - Hepatitis B virus-related insertional mutagenesis occurs frequently in human
      liver cancers and recurrently targets human telomerase gene.
AB  - Integration of Hepatitis B Virus (HBV) DNA into liver cell DNA has been well
      established, but its implication in liver carcinogenesis is still being debated.
      In particular, insertion of the viral genome into cellular genes has been viewed
      as a rare event. By using HBV-Alu PCR, we have now isolated, from nine
      hepatocellular carcinomas, nine HBV-DNA integration sites showing that the viral
      genome mutates key regulatory cellular genes: neurotropic tyrosin receptor kinase
      2 (NTRK2) gene, IL-1R-associated kinase 2 (IRAK2) gene, p42 mitogen-activated
      protein kinase 1 (p42MAPK1) gene, inositol 1,4,5-triphosphate receptor type 2
      (IP3R2) gene, inositol 1,4,5-triphosphate receptor (IP3R) type 1 (IP3R1) gene,
      alpha 2,3 sialyltransferase (ST3GAL VI or SITA) gene, thyroid hormone uncoupling
      protein (TRUP) gene, EMX2-like gene, and human telomerase reverse transcriptase
      (hTERT) gene. This result brings to 15 the total number of genes targeted by HBV
      in a study of 22 human liver cancers. Overall, we found that both the inositol
      1,4,5-triphosphate receptor gene and the telomerase gene were targeted by HBV in
      two different tumors. Thus, HBV frequently targets cellular genes involved in
      cell signalling and some of them may be preferential targets of the viral
      integration.

PMID- 12813465
TI  - Tenascin-C blocks cell-cycle progression of anchorage-dependent fibroblasts on
      fibronectin through inhibition of syndecan-4.
AB  - Tenascin-C is an adhesion-modulatory extracellular matrix protein that is
      predominantly expressed during embryonic development, wound healing and in tumor
      stroma. Here we report that anchorage-dependent human, rat and mouse fibroblasts
      adhere poorly and fail to proliferate on pure tenascin-C. This was due to a
      significant reduction of cyclin-dependent kinase 2 (cdk2) activity, resulting
      from elevated expression and association of the cdk inhibitors (CKIs) p21Cip1 and
      p27Kip1. To analyse the effect of tenascin-C on fibronectin-mediated adhesion,
      cells were plated on a mixed fibronectin/tenascin-C substratum. Compared to
      fibronectin alone, cell spreading and adhesion signaling were compromised, as
      determined by delayed phosphorylation kinetics of focal adhesion kinase (FAK).
      Despite the presence of growth factors, these cells remained arrested in the G1
      phase of the cell cycle. In contrast to cells plated on pure tenascin-C, cdk2
      activity appeared to be inhibited independently of CKIs. Interestingly,
      overexpression of the transmembrane proteoglycan syndecan-4 restored cell
      spreading, adhesion signaling and DNA replication on the fibronectin/tenascin-C
      substratum. A similar rescue was observed using a recombinant peptide that spans
      the syndecan-4-binding site in fibronectin. This indicates that tenascin-C causes
      cell cycle arrest and cdk2 inactivation by interfering with fibronectin-syndecan
      4 interactions. We therefore propose that syndecan-4 signaling plays a central
      role in the control of cellular proliferation of anchorage-dependent fibroblasts.

PMID- 12813466
TI  - Mitochondrial membrane permeabilization is a critical step of lysosome-initiated
      apoptosis induced by hydroxychloroquine.
AB  - Hydroxychloroquine (HCQ) is a lysosomotropic amine with cytotoxic properties.
      Here, we show that HCQ induces signs of lysosomal membrane permeabilization
      (LMP), such as the decrease in the lysosomal pH gradient and the release of
      cathepsin B from the lysosomal lumen, followed by signs of apoptosis including
      caspase activation, phosphatidylserine exposure, and chromatin condensation with
      DNA loss. HCQ also induces mitochondrial membrane permeabilization (MMP), as
      indicated by the insertion of Bax into mitochondrial membranes, the
      conformational activation of Bax within mitochondria, the release of cytochrome c
      from mitochondria, and the loss of the mitochondrial transmembrane potential. To
      determine the molecular order among these events, we introduced inhibitors of LMP
      (bafilomycin A(1)), MMP (Bcl-X(L), wild-type Bcl-2, mitochondrion-targeted Bcl-2,
      or viral mitochondrial inhibitor of apoptosis from cytomegalovirus), and caspases
      (Z-VAD.fmk) into the system. Our data indicate that caspase-independent MMP is
      rate-limiting for LMP-mediated caspase activation. Mouse embryonic fibroblasts
      lacking the expression of both Bax and Bak are resistant against
      hydroxychloroquine-induced apoptosis. Such Bax(-/-) Bak(-/-) cells manifest
      normal LMP, yet fail to undergo MMP and subsequent cell death. The data reported
      herein indicate that LMP does not suffice to trigger caspase activation and that
      Bax/Bak-dependent MMP is a critical step of LMP-induced cell death.

PMID- 12813467
TI  - Phospholipase D confers rapamycin resistance in human breast cancer cells.
AB  - mTOR (mammalian target of rapamycin) is a protein kinase that regulates cell
      cycle progression and cell growth. Rapamycin is a highly specific inhibitor of
      mTOR in clinical trials for the treatment of breast and other cancers. mTOR
      signaling was reported to require phosphatidic acid (PA), the metabolic product
      of phospholipase D (PLD). PLD, like mTOR, has been implicated in survival
      signaling and the regulation of cell cycle progression. PLD activity is
      frequently elevated in breast cancer. We have investigated the effect of
      rapamycin on breast cancer cell lines with different levels of PLD activity. MCF
      7 cells, with relatively low levels of PLD activity, were highly sensitive to the
      growth-arresting effects of rapamycin, whereas MDA-MB-231 cells, with a 10-fold
      higher PLD activity than MCF-7 cells, were highly resistant to rapamycin.
      Elevating PLD activity in MCF-7 cells led to rapamycin resistance; and inhibition
      of PLD activity in MDA-MB-231 cells increased rapamycin sensitivity. Elevated PLD
      activity in MCF-7 cells also caused rapamycin resistance for S6 kinase
      phosphorylation and serum-induced Myc expression. These data implicate mTOR as a
      critical target for survival signals generated by PLD and suggest that PLD levels
      in breast cancer could be a valuable indicator of the likely efficacy of
      rapamycin treatment.

PMID- 12813468
TI  - Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic
      mechanism in gastric cancer cells.
AB  - DLC-1 (deleted in liver cancer) gene is frequently deleted in hepatocellular
      carcinoma. However, little is known about the genetic status and the expression
      of this gene in gastric cancer. In this study, Northern and Southern analysis
      showed that seven of nine human gastric cancer cell lines did not express DLC-1
      mRNA, but contained the DLC-1 gene. To identify the mechanism of the loss of DLC
      1 mRNA expression in these cell lines, we investigated the methylation status of
      DLC-1 gene by using methylation-specific PCR (MSP) and Southern blot, and found
      that five of seven DLC-1 nonexpressing gastric cancer cell lines were methylated
      in the DLC-1 CpG island. Treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) induced
      DLC-1 mRNA expression in the gastric cancer cell lines that have the methylated
      alleles. Studies using SNU-601 cell line with methylated DLC-1 alleles revealed
      that nearly all CpG sites within DLC-1 CpG island were methylated, and that the
      in vitro methylation of the DLC-1 promoter region is enough to repress DLC-1 mRNA
      expression, regardless of the presence of transcription factors capable of
      inducing this gene. In all, 29 of 97 (30%) primary gastric cancers were also
      shown to be methylated, demonstrating that methylation of the DLC-1 CpG island is
      not uncommon in gastric cancer. In addition, we demonstrated that DLC-1 mRNA
      expression was induced, and an increase in the level of acetylated H3 and H4 was
      detected by the treatment with trichostatin A (TSA) in two DLC-1 nonexpressing
      cell lines that have the unmethylated alleles. Taken together, the results of our
      study suggest that the transcriptional silencing of DLC-1, by epigenetic
      mechanism, may be involved in gastric carcinogenesis.

PMID- 12813469
TI  - Chronic myelogenous leukemia molecular signature.
AB  - To obtain comprehensive information about the genes involved in BCR/ABL-dependent
      leukemogenesis, samples from 15 chronic myelogenous leukemia (CML) patients and
      seven normal donors were analysed using a cDNA microarray assay. After
      subtraction of the artificial, random or cross-hybridization signals, data about
      5315 genes have been effectively analysed in all samples. The assay revealed >/=4
      fold difference in the average expression of 263 genes in all CML samples when
      compared to normal counterparts, with 148 genes being upregulated and 115 being
      downregulated. Differentially expressed genes include those associated with
      BCR/ABL-induced abnormalities in signal transduction, gene transactivation, cell
      cycle, apoptosis, adhesion, DNA repair, differentiation, metabolism and malignant
      progression. Interestingly, CML-blast crisis cells in peripheral blood differ
      from those from bone marrow, indicating major changes in gene expression profiles
      upon entering into the bloodstream. Moreover, BCR/ABL modulates expression of
      genes, which are involved in regulation of chromosome/chromatin/DNA dynamics
      during S and M cell cycle phase. Moreover, the ability of CML cells to recognize
      and respond to a pathogen infection may be compromised. Altogether, this work
      provides a large body of information regarding gene expression profiles
      associated with CML and also represents a source of potential targets for CML
      therapeutics.

PMID- 12813470
TI  - Laser capture microdissection-based in vivo genomic profiling of wound
      keratinocytes identifies similarities and differences to squamous cell carcinoma.
AB  - Keratinocytes undergo a dramatic phenotypic conversion during reepithelialization
      of skin wounds to become hyperproliferative, migratory, and invasive. This
      transient healing response phenotypically resembles malignant transformation of
      keratinocytes during squamous cell carcinoma progression. Here we present the
      first analysis of global changes in keratinocyte gene expression during skin
      wound healing in vivo, and compare these changes to changes in gene expression
      during malignant conversion of keratinized epithelium. Laser capture
      microdissection was used to isolate RNA from wound keratinocytes from incisional
      mouse skin wounds and adjacent normal skin keratinocytes. Changes in gene
      expression were determined by comparative cDNA array analyses, and the approach
      was validated by in situ hybridization. The analyses identified 48 candidate
      genes not previously associated with wound reepithelialization. Furthermore, the
      analyses revealed that the phenotypic resemblance of wound keratinocytes to
      squamous cell carcinoma is mimicked at the level of gene expression, but notable
      differences between the two tissue-remodeling processes were also observed. The
      combination of laser capture microdissection and cDNA array analysis provides a
      powerful new tool to unravel the complex changes in gene expression that underlie
      physiological and pathological remodeling of keratinized epithelium.

PMID- 12813471
TI  - A comprehensive analysis of HPV integration loci in anogenital lesions combining
      transcript and genome-based amplification techniques.
AB  - Persistent infections with high-risk human papillomaviruses (HPVs) induce
      dysplastic lesions of the lower genital tract. Some of these lesions eventually
      progress to invasive cancers, particularly of the uterine cervix. In many
      advanced preneoplastic cervical lesions and most derived carcinomas, HPV genomes
      are found to be integrated into the host cell chromosomes. Although HPV
      integration seems to play an important role in the progression of cervical
      dysplasia, the underlying mechanisms are still unclear. To investigate the
      pathogenic role of genomic integration of HPV genomes in greater detail, we
      analysed integration sites of HPV16 and 18 genomes in 21 anogenital precancerous
      and cancerous lesions using a ligation-mediated chain reaction (DIPS) and the
      recently described amplification of papilloma virus oncogene transcripts (APOT)
      assay. On the genomic level, only singular integration events were observed in
      individual neoplastic cell clones. At many integration sites, a short overlap
      between HPV and genomic sequences was observed, suggesting that the integration
      of HPV genomes is mediated by nonhomologous sequence-specific recombination. APOT
      analysis revealed that the majority of integrated HPV genomes was actively
      transcribed. These data suggest that in the progression of cervical preneoplasia
      to invasive carcinomas, integration of viral genomes occurs only at single or few
      chromosomal loci in a given cell clone. Disruption of cellular genes might
      support malignant transformation in rare cases; however, it is not a pathogenic
      prerequisite. The main function of HPV integration seems to be the stabilization
      of oncogene transcription.

PMID- 12813472
TI  - A functional polymorphism of the mu-opioid receptor gene is associated with
      naltrexone response in alcohol-dependent patients.
AB  - This study examined the association between two specific polymorphisms of the
      gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent
      patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of
      European descent) who were randomized to naltrexone and 59 who were randomized to
      placebo (all of European descent) in one of three randomized, placebo-controlled
      clinical trials of naltrexone were genotyped at the A(+118)G (Asn40Asp) and
      C(+17)T (Ala6Val) SNPs in the gene encoding the mu-opioid receptor (OPRM1). The
      association between genotype and drinking outcomes was measured over 12 weeks of
      treatment. In subjects of European descent, individuals with one or two copies of
      the Asp40 allele treated with naltrexone had significantly lower rates of relapse
      (p=0.044) and a longer time to return to heavy drinking (p=0.040) than those
      homozygous for the Asn40 allele. There were no differences in overall abstinence
      rates (p=0.611), nor were there differences in relapse rates or abstinence rates
      between the two genotype groups among those assigned to placebo. These
      preliminary results are consistent with prior literature demonstrating that the
      opioid system is involved in the reinforcing properties of alcohol and that
      allelic variation at OPRM1 is associated with differential response to a mu
      receptor antagonist. If replicated, these results would help to identify alcohol
      dependent individuals who may be most likely to respond to treatment with
      naltrexone.

PMID- 12813473
TI  - Emerging evidence for a central epinephrine-innervated alpha 1-adrenergic system
      that regulates behavioral activation and is impaired in depression.
AB  - Currently, most basic and clinical research on depression is focused on either
      central serotonergic, noradrenergic, or dopaminergic neurotransmission as
      affected by various etiological and predisposing factors. Recent evidence
      suggests that there is another system that consists of a subset of brain
      alpha(1B)-adrenoceptors innervated primarily by brain epinephrine (EPI) that
      potentially modulates the above three monoamine systems in parallel and plays a
      critical role in depression. The present review covers the evidence for this
      system and includes findings that brain alpha(1)-adrenoceptors are instrumental
      in behavioral activation, are located near the major monoamine cell groups or
      target areas, receive EPI as their neurotransmitter, are impaired or inhibited in
      depressed patients or after stress in animal models, and are restored by a number
      of antidepressants. This "EPI-alpha(1) system" may therefore represent a new
      target system for this disorder.

PMID- 12813474
TI  - Altering cortisol level does not change the pleasurable effects of
      methamphetamine in humans.
AB  - Preclinical studies have linked corticosteroid secretion and levels with drug
      self-administration by animals. In a double-blind, cross-over study, subjective,
      physiological, and endocrine responses to intravenous doses of methamphetamine
      0.5 mg/kg or placebo were assessed in eight methamphetamine-experienced subjects
      after three cortisol-modifying premedication conditions: augmenting cortisol
      level with oral hydrocortisone 50 mg, blocking cortisol response with the
      corticosteroid synthesis inhibitor metyrapone 1500 mg orally, or no
      premedication. Although the pharmacologic manipulations produced the expected
      hormonal changes, subjective response to the methamphetamine showed few
      differences. Diminishing cortisol response by pharmacologic blockade did not
      alter the pleasurable effects of methamphetamine. Hydrocortisone did increase
      self-reported 'bad drug effect' and decreased craving after saline placebo
      relative to the period following methamphetamine. Metyrapone was associated with
      significant premature ventricular complexes in two subjects during
      methamphetamine administration and may not be safe for those who use
      methamphetamine.

PMID- 12813475
TI  - Dopamine depletion and in vivo binding of PET D1 receptor radioligands:
      implications for imaging studies in schizophrenia.
AB  - Recent positron emission tomography (PET) studies have assessed the level of
      dopamine (DA) D1 receptors in the prefrontal cortex (PFC) in patients with
      schizophrenia and have generated contradictory findings. In the PFC of patients
      with schizophrenia, the binding potential (BP) of [11C]NNC 112 has been reported
      as increased, while the BP of [11C]SCH 23390 was reported as decreased or
      unchanged. In this study, the effect of acute and subchronic DA depletion on the
      in vivo binding of [11C]NNC 112 and [3H]SCH 23390 was evaluated in rats. Acute DA
      depletion did not affect [11C]NNC 112 in vivo binding, but paradoxically
      decreased [3H]SCH 23390 in vivo binding. Subchronic DA depletion was associated
      with increased [11C]NNC 112 in vivo binding and decreased [3H]SCH 23390 in vivo
      binding. Together, these data demonstrate that the in vivo binding of these
      radiotracers is differentially affected by changes in endogenous DA tone, and
      suggest that alterations in the binding of these tracers in the PFC of patients
      with schizophrenia might reflect changes in D1 receptors secondary to sustained
      deficit in prefrontal DA function.

PMID- 12813476
TI  - [The state of poisoning in Navarra].
AB  - We briefly comment on the state of clinical toxicology in Navarra and in the rest
      of Spain, with reference to the Toxicology Committee of Navarra and its aims.
      Epidemiological data from the Emergency Service of the Hospital of Navarra is
      presented, as well as where to find information on the subject; the
      epidemiological registration sheet designed by the SEMESTOX group is attached. A
      description is given of the characteristics of therapeutic drugs and drugs of
      abuse determination (type of sample, methodology and interpretation of results)
      carried out in the toxicological analytical unit of the Hospital of Navarra.
      Finally, reference is made to all of the antidotes available to the Pharmacy
      Service of the Hospital of Navarra, which is the reference center for the whole
      of the autonomous community of Navarra. A description is given for each medicine
      including its indications.

PMID- 12813477
TI  - [General care of the intoxicated patient].
AB  - In this chapter we first set out the epidemiology of Clinical Toxicology, with
      the most frequent poisonings, and the need for making a register at the national
      level in order to obtain a more exact understanding of the true scale of the
      problem is emphasised. We next refer to clinical care and we divide patients
      depending on whether they have symptoms of: reduction in level of consciousness,
      alterations in their behaviour (agitation, delirium), generalized convulsions, or
      if they are conscious patients with different clinical manifestations: cardiac,
      pulmonary, digestive, nephro-urologic. Reference is also made to the
      neurotoxicological syndromes that can appear with different poisonings, besides
      the explorations and analyses that must be carried out to obtain an exact
      diagnosis of the poisoning. Finally, we deal with the treatment of the patient
      suffering form poisoning; we emphasise digestive decontamination, antidotes,
      kidney cleansing and the different poisonings that can be effective for extra
      renal cleansing.

PMID- 12813478
TI  - [Acute pharmacologic poisoning (I). Psychotropic and antiarrhythmic drugs].
AB  - In the evaluation of Acute Drug Poisoning (ADP) in patients seriously ill with a
      potentially non-toxic dose of the drug that is theoretically responsible, it is
      important to insist on anamnesis in the coingestion of other drugs or toxics.
      Initially attention is given to life support measures, oxygenation, protection of
      the airway and expanding the volemia. The ECG is a diagnostic tool of the first
      order in ADPs, above all for tricyclic antidepressants (TAD) and cardio-vascular
      drugs. In the majority of cases continuous monitoring is usually necessary during
      the first 12-24 hours. The benzodiazepines do not usually give rise to serious
      poisoning. The use of flumazenil will be reserved for cases of respiratory
      depression, deep coma or where the cause is undetermined. They can give rise to
      convulsions, above all in the case of mixed poisonings with anti-depressants and
      abstinence syndrome. The TADs have an enormous potential seriousness, as they can
      cause mortal arrhythmias. The therapeutic range of lithium is very narrow; it can
      produce signs of basically digestive and neurological toxicity. In the case of
      poisoning by digoxin, the use of anti-digital anti-bodies will be considered in
      cases of serious bradyarrhythmias, AV blocks or PCR. Glucagon is the antidote for
      serious poisoning by beta-blockers and for refractory hypotension in cases of
      calcioantagonists.

PMID- 12813479
TI  - [Acute pharmacologic poisoning (II). Analgesics and anticonvulsants].
AB  - In this second chapter on Acute Drugs Poisoning we deal with two groups of
      substances of great transcendence from the point of view of their use and
      morbidity/mortality. Within the group of analgesic-anti-inflammatory drugs we
      consider paracetamol and the salicylates, which are easily available to the
      population. With respect to the anticonvulsants, although they are barely
      involved in the ensemble of acute drug poisonings, their effects can be serious.
      We concentrate on four drugs: valproic acid, phenobarbitol, carbamacepine, and
      phenytoin. Finally, a section is dedicated to isoniazid, a drug that, with the
      renewed incidence of tuberculosis, is of toxicological interest.

PMID- 12813480
TI  - [Drug poisoning].
AB  - A review is made of acute poisoning by opiates and its treatment in the emergency
      services, bearing in mind the progressive decline in the number of cases
      presented with the arrival of new forms of their administration, as well as the
      presence of new addictive drugs that have resulted in a shift in consumption
      habits. Reference is also made to the way in which the different types of
      existing substances originated, with the aim of achieving a better understanding
      of their use and in order to administer the most suitable treatment when
      poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical
      picture, diagnosis and treatment. The consumption of illegal drugs in our country
      has undergone a notable change in recent years, with heroin being relegated and
      the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA),
      "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of
      cannabis and its derivates, from the history of its consumption and the
      preparations employed to the effects produced in the different bodily systems. A
      brief explanation is also given of its metabolites and its principal mechanisms
      of action. Finally, we comment on the effects of LSD and hallucinogenic
      mushrooms.

PMID- 12813481
TI  - [Alcohol intoxication].
AB  - Alcohol intoxication is the principal drug addiction in many countries of the
      world. It affects all age groups, both sexes and almost all social groups.
      Mortality associated with acute alcohol poisoning on its own is exceptional, but
      it can be an important factor if it coexists with recreational drugs. It is
      directly responsible for more than half of traffic accidents. Diagnosis is easy
      by means of anamnesis and clinical examination, and can be confirmed by
      determining the level of ethanol in the bloodstream. Supportive care is the best
      therapy in order to protect the patient from secondary complications. Methanol,
      or alcohol fuel, is used as a solvent, and can also be found as an adulterant of
      alcoholic drinks. Poisoning by oral means is the most frequent. Oxidized in the
      liver through dehydrogenase enzyme alcohol, toxicity is due to its metabolites,
      formaldehyde and formic acid. The clinical picture basically consists of
      cephalea, nausea, vomiting, hypotension and depression of the central nervous
      system. The optic nerve is especially sensitive, with total and irreversible
      blindness as a possible result. Ethylenglicol is used as a solvent and as an
      antifreeze; toxicity is due to an accumulation of its metabolites. The clinical
      picture includes symptoms that are held in common with methylalcohol
      intoxication. Kidney failure due to tubular necrosis and the deposit of oxalate
      crystals can occur.

PMID- 12813482
TI  - [Metal poisoning].
AB  - Metals are amongst the oldest toxic substances known to man. In today's
      industrialized world the sources of exposure to metals are ubiquitous both in the
      field of work and from polluted water, foodstuffs and the environment. Their
      toxicity is characterized by the metallic element in question, but this is
      modified by the type of compound, whether organic or inorganic, and its
      characteristics of hydrosolubility and liposolubility, which determines its
      toxicokinetics and thus the possibilities of it reaching its targets. The
      biomolecules most affected by metals are the proteins with enzymatic activity,
      which is why their pathology is multisystemic. The principal systems affected are
      the gastrointestinal, central and peripheral neurological, haematic and renal.
      Some metallic compounds are carcinogenic. Metals's treatment is conditioned by
      their chemical reactivity. They can be deactivated and eliminated by the
      administering of chelating agents that produce complex molecules, which are non
      toxic and can be excreted. The principal chelating agents are: BAL (British Anti
      Lewisite or dimercaprol) DMPS (2,3-Dimercapto-1-propanesulfonic Acid) and DMSA
      (meso-2,3-Dimercaptosuccinic or Succimer), EDTA, Penicilamine (b,b
      dimethylcysteine) and Deferoxamine. Toxicokinetic characteristics, mechanism of
      action, clinical picture and treatment of some of the most relevant metals and
      metalloids: lead, mercury and arsenic, are considered.

PMID- 12813483
TI  - [Pesticide poisoning].
AB  - Pesticides are one of the families of chemical products most widely used by man.
      They have been used above all to combat pests because of their effect on harvests
      and as vectors of transmissible diseases. Pesticides can be classified according
      to their use (insecticides, fungicides, herbicides, raticides em leader ) or by
      their chemical family (organochlorates, organophosphates, carbamates,
      pyrethroids, Bipyridilium compounds, inorganic salts em leader ). All of them are
      biocides, which normally implies a high toxicity for humans, which has been a
      cause for concern since the mid-XX century due to the widespread and
      indiscriminate use of these products. Exposure to pesticides can have effects
      that are acute, chronic and long-term. Some organochlorate compounds (such as
      DDT) were the first to be used in massive fumigations to fight malaria and have
      had to be banned because of their capacity for bioaccumulation and environmental
      persistence. The danger represented by the widespread presence of these agents
      has been demonstrated in numerous episodes of human toxic epidemics, producers of
      a high morbidity/mortality, described for nearly all chemical families:
      organochlorate insecticides and fungicides, organophosphate and carbamate
      insecticides, organomercurial fungicides and inorganic salts. These episodes have
      above all been caused through the ingestion of foodstuffs and in the occupational
      field. Other causes of health concern are their carcinogenic capacity and
      occasional reproductive alterations. The principal characteristics of some of the
      most relevant families are presented.

PMID- 12813484
TI  - [Gas poisoning].
AB  - Poisoning by gases in our area is an important problem due to its high incidence.
      In the specific case of carbon monoxide poisoning, this is the main cause of
      death by poisoning in our environment, on many occasions coexisting with cyanide
      poisoning. Both poisonings can be severe, their diagnosis being based on the mere
      suspicions of the doctor. Besides, their importance lies in the fact that both
      poisonings have a very specific treatment. Normo or hyperbaric oxygenotherapy is
      the treatment for carbon monoxide poisoning. In the case of cyanide poisoning,
      hydroxocobalamin is nowadays the treatment of choice, since it has proved itself
      to be an efficient antidote.

PMID- 12813485
TI  - [Contamination by chemical agents].
AB  - Contamination by chemical products is a clinical situation whose handling
      requires very specific knowledge by the physicians in the emergency services,
      since they must know the most frequent types of chemical agents and their
      mechanism of action. This type of contamination makes it necessary for there to
      be concrete plans of action in the hospital milieu and coordination with the
      emergency outpatient mechanisms. To the risk of being surrounded by chemical
      products on an industrial scale on a daily basis, and the risk of leaks and
      accidents during transport and even in private homes, there is now added the
      possible use of different chemical agents as weapons of mass destruction, both in
      military conflicts and in terrorist acts.

PMID- 12813486
TI  - [Posioning by caustic substances].
AB  - There are discordant guides and protocols when it comes to treating a patient who
      has ingested a caustic substance. Different ideas or tendencies speak in favour
      of dilution, neutralization, provoking vomiting, carrying out stomach washes,
      etc., depending on the milieu where the problem arises: at home, at the health
      centre, emergency service or hospital. The same occurs with the type of diluent
      or neutralizing agent to be used, how and when to start the treatment pattern
      with corticoids and/or antibiotics and antisecretory, if indeed this is
      necessary. We have carried out an exhaustive bibliographical study, an
      experimental work and a study of the different diagnosis and treatment guides and
      protocols used in different Spanish hospitals. At the experimental level it was
      found that there are histopathological markers that advise against the use of
      diluent substances following the ingestion of caustic alkali. Except in the cases
      of ingestion of solid caustic substances -crystalline or granulated- categorical
      contraindications are given against dilution. Corticoids are not efficient when a
      caustic acid is ingested; their use is more than questionable following the
      ingestion of caustic alkali. Diagnosis and quality of treatment are based on
      endoscopy. There is no single criterion that defines which moment (the time
      following ingestion) is the most convenient for carrying this out, although the
      period between the first 6-12 hours is the most suitable. We present an
      independent protocol of diagnosis and treatment -in the form of algorithms- that
      must be followed after the ingestion of caustic acids or caustic alkali.

PMID- 12813487
TI  - [Poisoning in children. Methaemoglobinaemia].
AB  - Poisonings during childhood account for 0.3-0.4% of consultations in the
      emergency pediatric services and constitute a pathology that must be born in
      mind, because of its frequency, its consumption of resources, its repercussion on
      the surrounding milieu and the possibility of its prevention. With respect to its
      epidemiology, the first cause of pediatric poisoning are medicines, with
      paracetamol outstanding as the most frequent cause of poisoning. In the second
      place in order of frequency we find products of household use, although their
      importance in pediatric toxicology rests basically on the fact that some of these
      products, such as cosmetics, can result in accidental ingestion, almost
      exclusively involving children. Hospital procedure concerning the poisoned child
      involves a first phase of life support and stabilization measures, followed by
      identification of the toxin and measures of detoxification where necessary. Given
      the broad scope of the issue and the impossibility of covering all of pediatric
      toxicology, this article describes its epidemiology in our milieu and some
      considerations are made with respect to dealing with the most frequent or
      characteristic poisonings involving children. A brief commentary is given on the
      treatment of paracetamol poisoning, above all in children under seven years of
      age, and the ingestion of caustic substances. Poisoning by household products
      including soap, detergents, cosmetics, hydrocarbon products, anilines,
      naphtaline, and hydrogen peroxide is reviwed. Finally, methaemoglobinaemia's
      physiopathology, aetiology, clinical picture, diagnosis and treatment is
      reviewed.

PMID- 12813488
TI  - [Animal sting and bites].
AB  - Under the heading of this subject we deal with stings by arthropods, making
      reference to the differences that exist between the stings of wasps and bees,
      commenting on the composition of the poisons and the different local and general
      reactions that are caused by such stings. Also discussed are the stings/bites
      caused by scorpions, spiders, ticks, and marine animals, with the clinical
      picture they provoke and the treatment that must be administered. Finally,
      snakebites are considered, with reference to the most frequent types of ophidia
      to be found in Navarra, how to differentiate between the bites of snakes and
      vipers, the different clinical pictures they provoke and the treatment to be
      applied

PMID- 12813489
TI  - [Poisoning by foodstuffs, plants and mushrooms].
AB  - Food poisoning is defined as poisoning caused by any foodstuff or alimentary
      product that causes poisoning because it contains toxic substances, germs,
      metals, additives, hormones, etc. It forms an important part of Clinical
      Toxicology, although in the majority of statistics, alimentary toxic infections
      provoked by bacteria, protozoa and viruses are not classified as poisonings,
      since they are caused by germs, and are classified as infections. Reference is
      made within this subject to all types of pathologies due to food, with special
      emphasis given to botulism. The clinical picture of botulism is discussed in its
      different clinical forms, but above all in its adult form which is contracted
      through the consumption of undercooked or badly preserved foods; poisoning by
      fish and seafood. Also described are the toxicological pictures that can be
      caused by the consumption of plants containing toxic substances, framed by the
      different symptomologies they produce; finally, poisonings by mushrooms are set
      out according to the period of incubation and possible confusions.

PMID- 12813490
TI  - [Poisonings at the workplace].
AB  - The number of workers who run the risk of showing a poisoning originating from
      their work is high: more than a quarter of the workers in Spain find themselves
      exposed to chemical products at their work place, and around 17% handle such
      products directly. There are numerous chemical agents that can cause poisonings
      in the workplace; the majority of these clinical pictures receive health care in
      the public health service and often their origin in the workplace is not
      recognized. According to the official registers of occupational diseases, 3 out
      of every 100,000 workers develop diseases produced by chemical agents each year;
      these registers do not allow to know the real magnitude of the problem due to the
      underreporting of cases and to poisonings reported as occupational accidents. It
      is a priority to improve the quality of the registers and to establish systems of
      complementary declaration for the occupational poisonings that are treated in
      emergency consultations, primary and specialized care. Clinical cases of some
      workers who showed poisonings related to their working activity could help to
      increase awareness of this health problem in daily practice

PMID- 12813491
TI  - [Legal aspects of toxicological care].
AB  - The care of poisoned patients in the sphere of the hospital emergency services is
      an increasingly frequent phenomenon. Any patient, whether or not they die, who is
      subjected to medical care in the course of a poisoning generates certain
      obligations from the medical-legal point of view. This paper reviews the most
      frequent causes of medical care in living patients, or in those who have died
      because of a poisoning, the legal obligations that care gives rise to, and the
      suitable form for approaching and resolving these.

PMID- 12813492
TI  - Abstracts of the 3rd International Conference on Inhibitors of Protein Kinases,
      June 22-27, 2003 and Workshop on Phosphoryl-Transfer Mechanisms, June 27-29,
      2003. Warsaw, Poland.

PMID- 12813559
TI  - The genetic characteristics Saccharomyces cerevisiae aci(+) mutants.
AB  - A series of 30 Saccharomyces cerevisiae aci(+) mutants (characterized as
      acidifying Ogur's glucose medium containing bromocresol purple) were isolated
      after EMS mutagenesis. All the mutants excreted acid metabolites to the medium
      after 24 or 48 hours of incubation. The character of the aci(+) mutations was
      defined using classical genetic techniques. Three of the aci(+) mutants were
      studied by molecular genetics techniques.

PMID- 12813560
TI  - Syndecan-4 distribution during the differentiation of satellite cells isolated
      from soleus muscle treated by phorbol ester and calphostin C.
AB  - It was shown that syndecans have a potential role in muscle development. We
      focused this study on the role of syndecan-4 distribution and phosphorylation
      during the differentiation of satellite cells isolated from Soleus muscle.
      Syndecans are cell surface heparan sulfate proteoglycans (HSPGs) that bind
      numerous ligands through their HS glycosaminoglycan chains (GAG). They play a
      role in cell-extracellular matrix and cell-cell adhesion, signal transduction and
      the targeting of growth factors and other molecules to the cell surface. Syndecan
      4 acts as a co-receptor or, along with integrins, is localized to the cell
      membrane of focal contacts. Syndecan-4 participates in the organization of the
      structure of focal contacts reacting with extracellular matrix molecules. The
      interaction of syndecan-4 with protein kinase C (PKC) isoforms is the main
      mechanism regulating its distribution in cells. Our current study focused on the
      role of the distribution of syndecan-4, and its interactions with PKC isoforms
      during the differentiation of activated satellite cells. We used the PKC
      activator TPA (12-O-tetradecanoyl phorbol 13-acetate) and the PKC inhibitor
      Calphostin C (Cal C). We concluded that syndecan-4 was important not only in the
      activation of satellite cells, but also in myoblast differentiation. During our
      research, we observed the presence of syndecan-4 and changes in its location over
      the course of that process. We also showed that TPA and Cal C treatment had an
      influence on the subcellular distribution of syndecan-4, but there was no
      influence on myoblast differentiation. We speculated that the reason for changes
      after TPA treatment was the interactions with activated PKC alpha, which provoked
      syndecan-4/PKC alpha complex translocation to integrins. We also supposed that
      Cal C treatment inhibited PKC delta activity and probably induced PKC lpha
      association to syndecan-4, and syndecan-4 translocation to integrins.

PMID- 12813562
TI  - Visual and archaeal rhodopsins: similarities, differences and controversy.
AB  - Rhodopsins are currently known to belong to two distinct protein families. The
      visual rhodopsins, found in eyes throughout the animal kingdom, are photosensory
      pigments. Archaeal rhodopsins, found in extreme halophiles, function as light
      driven proton pumps (bacteriorhodopsins), chloride ion pumps (halorhodopsins), or
      photosensory receptors (sensory rhodopsins). Light absorption by rhodopsins
      triggers their characteristic photoconversion extending into the (milli)second
      time range. There are three main paradigms of rhodopsins photoconversion. (1)
      Initiation of the trans-cis isomerization is the very primary consequence of
      light absorption. (2) Rhodopsins store light energy via the charge-separation
      mechanism (the charge of Schiff base is separated from its counterion). (3) Full
      trans-cis isomerization of the chromophore is a prerequisite for the full
      biological activity of rhodopsins. These paradigms will be questioned.

PMID- 12813561
TI  - The activity of lipoxygenase in Arabidopsis thaliana (L.) Heynh -- a preliminary
      study.
AB  - The activity of lipoxygenase (EC 1.13.11.12) in Arabidopsis thaliana (L.) Heynh
      seedlings and mature plants was estimated spectrophotometrically at 234 nm.
      Linoleic acid was used as a substrate. Lipoxygenase activity showed two pH
      optima: at 7.0 and 10.0 in seedlings, and at pH 8.0 and 10.0 in leaves of mature
      plants. Seven-week-old plants were transferred to a hydroponic system and treated
      with different concentrations of Cd(2+) or Cu(2+) [in microM]: 0, 5, 25, 50, 100
      for 7 days. The lipoxygenase activities at pH 8.0 and 10.0 depended on the metal
      that was added to the nutrient solution. The main change in lipoxygenase activity
      was under Cd(2+)stress at pH 8.0 and under Cu(2+)excess at pH 10.0.

PMID- 12813563
TI  - Histological pictures of muscles and an evaluation of cellular infiltrations in
      human polymyositis/dermatomyositis, as compared to the findings in experimental
      Guinea pig myositis.
AB  - We tested whether intramuscular injections of dermatomyositis (DM) patients' sera
      into guinea pig muscles can be used to transfer myositic alterations to these
      animals. Additionally, similar tests were performed using neoplastic patients'
      sera and sera from non-neoplastic, non-myositic patients. The DM patients' sera
      induced idiopathic inflammatory myopathy (IIM) type histological changes in
      muscle fibres in guinea pig quadriceps muscles, which were especially evident 72
      h after sera injections. Immunohistochemical stainings of myositic guinea pig
      muscles were done for guinea pig pan-T-cells, monocytes/macrophages, the neuronal
      marker-protein gene product 9.5 (PGP 9.5) and protein S-100. Our studies proved
      that the factor(s) responsible for the appearance of characteristic alterations
      in diseased muscles during the course of DM is/are present in patient sera.

PMID- 12813564
TI  - The optimal eukaryotic signal for translation initiation from non-AUG codons,
      present upstream of bacteriophage lambda P cistron, is inactive in Escherichia
      coli.
AB  - Expression of the replication genes of bacteriophage lambda, O and P, is believed
      to be translationally coupled. However, it was previously noted that, under
      conditions of amino acid starvation, when O is not synthesized, P continues to be
      expressed at a relatively high level. The results presented in this report,
      contrary to the previously presented hypothesis, suggest that an AGACUGGAU
      sequence (an optimal context for translation initiation from non-AUG codons in
      eukaryotes, and present upstream the P cistron) is inactive in Escherichia coli.
      Comparative sequence analysis confirms that such a signal is unlikely to be
      important for P synthesis. Instead, a weak Shine-Dalgarno sequence may be present
      upstream the P cistron, and be active in the absence of O gene expression.

PMID- 12813565
TI  - There is no evidence for the existence of complex formation between doxorubicin
      and glutathione.
AB  - Doxorubicin is co-transported with glutathione by several multidrug resistance
      proteins (MRPs). In order to check whether weak non-covalent aggregates between
      doxorubicin and glutathione can be formed, which might be substrates for the
      transporter, the effect of glutathione on the partition coefficient of
      doxorubicin was studied. No evidence of an effect of glutathione (at levels up to
      20 microM) on the partition coefficient of doxorubicin was found in the pH range
      of 4.0-7.4. These results indicate that non-covalent doxorubicin-glutathione
      complexes do not form.

PMID- 12813566
TI  - The role of STAT5 proteins in the regulation of normal hematopoiesis in a cord
      blood model.
AB  - The signal transducers and activators of transcription - STAT5A and STAT5B - are
      responsible for the control of proliferation, differentiation and apoptosis, via
      their effect on gene expression. They are activated by the binding of many
      cytokines, growth factors and hormones to their receptors on the cell surface.
      Many of these cytokines regulate hematopoietic cell development; therefore, STAT5
      proteins are suggested to play an important role in hematopoiesis. There are
      numerous contradictory reports available in the literature on the role of STAT5
      in normal hematopoietic cell development; hence, the question of the real
      function of STAT5 proteins clearly requires further studies. The aim of our study
      was to evaluate the role of STAT5 in normal hematopoiesis using
      oligodeoxynucleotide (ODN) strategy against STAT5 mRNA. We employed the RT-PCR
      method to study STAT5 mRNA expression in cells after their incubation with ODNs.
      We analyzed the effect of blocking STAT5 proteins on the viability and
      clonogenecity of the CFU-GM (Colony Forming Unit of Granulocyte-Macrophages) and
      the BFU-E (Burst Forming Unit of Erythrocytes) obtained from human cord blood
      (CB). The clonogenic growth of the cells was assessed in methylcellulose cultures
      according to the type of oligodeoxynucleotides. We also attempted to estimate the
      level of apoptosis induced in cord blood mononuclear and CD34+ cells by employing
      different assays: i) Annexin V staining using flow cytometry (FACSCalibur); ii)
      terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL); iii)
      analysis of Bax and Bcl-X(L) gene expression by RT-PCR. Perturbation of STAT5
      expression with antisense oligodeoxynucleotides had no impact on the viability,
      clonogenecity and apoptosis of CB hematopoietic cells. Our results showed that
      STAT5 proteins do not play a significant role in the regulation of proliferation
      of normal hematopoietic cells derived from cord blood.

PMID- 12813567
TI  - The effect of melatonin on antioxidant enzymes in human diabetic skin
      fibroblasts.
AB  - Melatonin plays several important physiological functions in mammals, such as
      immune enhancement and regulation of dark-light signal transduction. Melatonin is
      also known to be an endogenous free radical scavenger and an efficient
      antioxidant. It detoxifies a variety of free radicals and reactive oxygen
      intermediates, including the hydroxyl radical, singlet oxygen and nitric oxide.
      These radicals participate in many diseases, for example diabetes. This study
      determined the effect of melatonin on the antioxidant enzymes: superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and the level
      of glutathione (GSH) in human diabetic (C2 line) skin fibroblasts. Confluent
      monolayers of control (S2 line) and diabetic (C2 line) skin fibroblasts were
      incubated with different concentrations of melatonin: 10, 50, 100 and 1000
      micromol/l at 37 degrees C for 24 h. Next, the GSH level and SOD, CAT and GPx
      activities were measured colorimetrically. The activities of the antioxidant
      enzymes and the GSH level were lower in diabetic skin fibroblasts than in the
      control S2 line. Concentrations of melatonin of 100 and 1000 micromol/l caused a
      significant increase in the enzymes' activities and GSH level.

PMID- 12813568
TI  - The influence of metmyoglobin and ferrylmyoglobin on the human erythrocyte
      membrane.
AB  - Preliminary experiments revealed that ferrylmyoglobin decayed more slowly in the
      absence than in the presence of intact erythrocytes and erythrocyte membranes.
      This suggested the existence of interactions between FerrylMb and the erythrocyte
      membrane. Subsequent studies examined the influence of FerrylMb on the membrane
      of intact erythrocytes and on isolated erythrocyte membranes. The incubation of
      intact erythrocytes with FerrylMb did not influence their osmotic fragility or
      the fluidity of their membranes; the level of peroxidation of the membrane lipids
      increased only slightly (there was only a slight increase in the level of
      membrane lipid peroxidation). The activity of acetylcholinesterase significantly
      increased after 15 minutes of incubation, whereas longer incubation did not lead
      to any changes in the activity of this enzyme. The incubation of isolated
      erythrocyte membranes with FerrylMb resulted in an increase in their fluidity and
      a significant rise in the level of lipid peroxidation.

PMID- 12813569
TI  - The anther-culture response of triticale line x tester progenies.
AB  - Seven triticale cultivars (Ampiac, Aubrac, Trinidad, Ticino, Lamberto, Pronto and
      Prado) and their F1 hybrids obtained after crossing in a line x tester scheme
      were examined with respect to their androgenetic effectiveness. The embryo
      induction rate (number of embryos per 100 anthers), green plant regeneration rate
      (number of green plantlets per 100 embryos), plant yield (number of green and
      albino plantlets per 100 anthers) and green plant yield (number of green
      plantlets per 100 anthers) were assessed. The multivariate and univariate effects
      of general (GCA) and specific (SCA) combining abilities for the studied traits
      were estimated and tested. Significant differences between the genotypes were
      found for individual traits as well as for all the traits treated jointly.
      Hybrids generally showed a better response in anther culture than their parental
      genotypes. Heterosis effects were observed in some hybrids for embryo induction
      rate and green plant yield. GCA and SCA variances were significant and a
      dominance of the GCA over the SCA variation was found. Among the examined
      cultivars, Ticino and Pronto were characterised by positive and significant GCA
      for embryo induction and green plant yield, and these cultivars may be
      recommended for the improvement of anther culture responsiveness in triticale.

PMID- 12813571
TI  - The use of immobilized methylchymotrypsin for the purification of human and sheep
      alpha-1-proteinase inhibitor (alpha(1)-PI).
AB  - alpha(1)-proteinase inhibitor was isolated from albumin fractions of human and
      sheep plasma using a new method of purification using affinity chromatography on
      immobilized methylchymotrypsin in the presence of 5 M NaCl. The inhibitor was
      finally polished to homogenity either by chromatography on a Mono Q or a
      Sephacryl S-200 HR column. The presented method makes it possible to recover
      alpha(1)-proteinase inhibitor which has been added to cow milk.

PMID- 12813570
TI  - The prion peptide forms ion channels in planar lipid bilayers.
AB  - One of the hypotheses concerning the pathogenic properties of the prion protein
      considers its influence on cellular ion homeostasis. Using the lipid bilayer
      technique, the influence of prion-derived peptides on the lipid bilayer
      conductance was characterized. To evaluate the physiological significance and
      possible pathological functions of the peptides, their effect on the membrane
      potential and respiration rate of hippocampal mitochondria was also studied. We
      used a peptide bearing the human prion protein sequence YSNQNNF (PrP [169-175]),
      and peptide SSQNNF (PrP [170-175]) bearing a naturally-occurring mutation in
      position 171 [N(r)S] linked to schizoaffective diseases in humans (Samaia, H.B.,
      Mari, J.J., Vallada, H.P., Moura R.P., Simpson A.J.G., Brentani R.R. A prion
      linked psychiatric disorder. Nature 390 (1997) 241). In this report, we show that
      PrP [170-175] N171S increases the conductance of planar lipid bilayers. Based on
      the conductance of single channel currents recorded in 500/500 mM KCl
      (cis/trans), we found a single channel conductance of 8 to 26 pS. The native
      prion peptide PrP [169-175] does not form ion channels in the lipid bilayer.
      Neither of the peptides significantly changed the membrane potential or
      respiration rate of isolated rat hippocampal mitochondria. We propose a possible
      mechanism for channel formation by aggregation of the prion-derived peptide.

PMID- 12813572
TI  - AFLP marker polymorphism in cucumber (Cucumis sativus L.) near isogenic lines
      differing in sex expression.
AB  - The AFLP technique was used to evaluate the level of polymorphism between two
      pairs of isogenic cucumber (Cucumis sativus L.) lines (NIL) differing in flower
      sex expression. The BSA techniques were also applied to find molecular markers
      linked to sex determination genes (dominant alleles) in those cucumber lines. Sex
      determination in cucumber is controlled by three main loci F, M and Gy. The
      interaction of these loci is responsible for the formation of the various
      phenotypes of flowers in respect to sex in the analyzed lines [corrected]. A
      female line 2gg with a ff/MM/gygy genotype, isogenic to a monoecious line B10
      (genotype ff/MM/GyGy), and a female line Gy3 with a FF/MM/GyGy genotype, isogenic
      to a hermaphroditic line HGy3 (genotype FF/mm/GyGy). Using 56 combinations of
      AFLP primers, used for the analysis of lines 2gg and B10, gave 3794 bands, of
      which 155 (4.1%) were polymorphic. Ten bands distinguished gynoecious and
      monoecious bulks appearing at the same time in the appropriate parent; they are
      believed to be linked to the Gy locus. The isogenic lines Gy3 and HGy3 showed a
      higher level of polymorphism (14.2%). In this case, 55 combinations of primers
      gave 2996 reaction products, of which 430 showed variation. Twenty bands occurred
      in one bulk and in one parent, so they are probably associated with the M locus.
      Using the AFLP technique, the isogenicity of the lines was evaluated. The level
      of polymorphism (per pair of primer) between lines 2gg and B10 is 0.072% and is
      four times lower than that between the Gy3 and HGy3 lines (0.27%). The
      differences in the isogenicity of the lines can result from the degree of their
      relatedness, which may reflect the way they were derived.

PMID- 12813573
TI  - The effect of the presence of crown ether on ion transport across the lipid
      bilayer.
AB  - We studied the electric properties of phosphatidylcholine bilayers modified with
      crown ether (dibenzo[18] crown-6). The studies were carried out for various crown
      ether concentrations in forming solutions and various potassium ion
      concentrations in electrolyte solutions. The presence of crown ether in the
      membrane influences the membrane's impedance; there is a reduction in its
      resistivity, a decrease in its resistance of phase transfer and an increase in
      its capacity of phase transfer with an increase in crown ether concentration in
      the bilayer and in K(+) ion concentration in the electrolyte solution.

PMID- 12813574
TI  - DNA damage caused by lipid peroxidation products.
AB  - Lipid peroxidation is a process involving the oxidation of polyunsaturated fatty
      acids (PUFAs), which are basic components of biological membranes. Reactive
      electrophilic compounds are formed during lipid peroxidation, mainly alpha, beta
      unsaturated aldehydes. These compounds yield a number of adducts with DNA. Among
      them, propeno and substituted propano adducts of deoxyguanosine with
      malondialdehyde (MDA), acrolein, crotonaldehyde and etheno adducts, resulting
      from the reactions of DNA bases with epoxy aldehydes, are a very important group
      of adducts. The epoxy aldehydes are more reactive towards DNA than the parent
      unsaturated aldehydes. The compounds resulting from lipid peroxidation mostly
      react with DNA showing both genotoxic and mutagenic action; among them, 4
      hydroxynonenal is the most genotoxic, while MDA is the most mutagenic. DNA damage
      caused by the adducts of lipid peroxidation products with DNA can be removed by
      the repairing action of glycosylases. The formed adducts have been hitherto
      analyzed using the IPPA (Imunopurification-(32)P-postlabelling assay) method and
      via gas chromatography/electron capture negtive chemical ionization/mass
      spectrometry (GC/EC NCI/MS). A combination of liquid chromatography with
      electrospray tandem mass spectrometry (LC/ES-MSMS) with labelled inner standard
      has mainly been used in recent years.

PMID- 12813575
TI  - A comparison of the total antioxidant capacity of some human body fluids.
AB  - The Total Antioxidant Capacity of several human fluids was compared and the
      following sequence of TAC values was found: urine > saliva > blood plasma > milk
      approximately amniotic fluid >> sweat. Lower TAC values were found for the saliva
      of smokers than for that of non-smokers. Drinking of a cup of instant coffee
      increased the hydrogen peroxide content of urine but did not decrease the TAC of
      urine.

PMID- 12813576
TI  - The isolation of cDNA clones from cucumber (Cucumis sativus L.) floral buds
      coming from plants differing in sex.
AB  - In this study, we found flower cDNA clones which may be connected with the
      development of flower sex in cucumber. Two pairs of nearly-isogenic lines:
      gynoecious GY3 (FFMMGG) versus hermaphrodite HGY3 (FFmmGG) and monoecious B10
      (ffMMGG) versus gynoecious 2gg (ffMMgg) were used for clone isolation. To obtain
      differentially-expressed clones, we applied the differential screening method.
      454 clones from GY3 and 478 from B10 cDNA libraries were isolated. The results of
      RFLP analysis with 56 cDNA clones showed no clones which cosegregated with sex in
      cucumber. The 28 cDNA B10 and 33 cDNA GY3 clones isolated using the differential
      screening method were sequenced. Some of them seem to may play a role in cell
      differentiation or flower development. Among the 61 identified clones, 14 show
      high homology to plant proteins, although of unknown function. 11 show high
      homology to known proteins, and the possible function of some of them is
      discussed. For 3 clones, no significant similarity was found. The 31 clones
      displayed high homology to plant cDNA in EST database. The patterns of expression
      of five differential cDNA clones, 35GY3, 216GY3, 47GY3, 100B10 and 157B10, were
      analyzed in cucumber flower buds using in situ RT-PCR. The most interesting clone
      is 35GY3, because of its possible role in the inhibition of the development of
      male specific elements in the female cucumber flower.

PMID- 12813577
TI  - A kinetics study of pig erythrocyte hemolysis induced by polyene antibiotics.
AB  - The kinetics of the hemolysis induced by filipin is of the damage type,
      indicating the formation of large nonselective perforations of erythrocyte
      membranes. The process is relatively independent of the ionic composition of the
      incubation medium, and the differences between the hemolysis induced by filipin
      in pig and human erythrocytes are not significant. In a sucrose medium, filipin
      induced hemolysis is inhibited in humans, whereas it is stimulated in pig
      erythrocytes. It is suggested that low ionic strength is the reason for the
      different modifications of complexation of filipin in pig and human erythrocyte
      membranes in a sucrose medium. The kinetics of the hemolysis induced in pig
      erythrocytes by amphotericin B and nystatin is of the permeability type,
      indicating the formation of selective channels in erythrocyte membranes and
      colloid osmotic hemolysis. The rate of the hemolysis, which is high in a KCl
      medium, is decreased in all the other media tested (CaCl2, MgCl2, potassium
      phosphate buffer, K2SO4, sucrose), although there are no changes in the kinetics
      of hemolysis. The results are interpreted as the formation of highly selective
      channels at a low concentration of the antibiotics. At increasing concentrations,
      channels of decreasing selectivity occur. The resistances of pig erythrocytes to
      amphotericin B and nystatin are lower than those of human erythrocytes.

PMID- 12813578
TI  - The effect of peroxynitrite and some antioxidants on the rate of osmotic
      hemolysis of bovine erythrocytes.
AB  - Bovine erythrocytes treated with peroxynitrite (ONOO(-)), a cytotoxic species
      formed in vivo via the reaction of nitric oxide (NO(.)) and the superoxide anion
      (O2(-.)), show an increased rate of hemolysis on sudden osmotic stress. The
      increase in the rate was peroxynitrite concentration dependent. In the presence
      of some antioxidants (uric acid, ascorbic acid, glutathione, melatonin and
      albumin), this effect was significantly lower, with ascorbic acid as the most
      efficient antioxidant.

PMID- 12813579
TI  - Prophylactic effect of melatonin in reducing lead-induced neurotoxicity in the
      rat.
AB  - Oxidative stress is a likely molecular mechanism in lead neurotoxicity.
      Considering the antioxidant properties of melatonin, this study investigated the
      neuroprotective potential of melatonin in the hippocampus and corpus striatum of
      rats treated with lead. Three groups of male rats (control, lead acetate-treated
      [100 mg/kg], and lead acetate plus melatonin [10 mg/kg] for 21 consecutive days)
      were used. Levels of products of lipid peroxidation (LPO), glutathione (GSH) and
      superoxide dismutase (SOD) activity were measured in brain homogenates.
      Histological changes in the pyramidal cells of the hippocampus and the putamen of
      the corpus striatum were examined. The results documented increased LPO and
      decreased GSH and SOD activity in the brain homogenates of lead-treated rats.
      Histological observations revealed severe damage and a reduction in neuronal
      density in the hippocampus and corpus striatum. When melatonin was given to lead
      treated rats, it almost completely attenuated the increase in LPO products and
      restored GSH levels and SOD activity. Also, the morphological damage was reduced
      and neuronal density was restored by melatonin. Considering the ease with which
      melatonin enters the brain, these results, along with previous observations,
      suggest that melatonin may be useful in combating free radical-induced neuronal
      injury that is a result of lead toxicity.

PMID- 12813580
TI  - The tumorigenic potential of human CX-1 colon adenocarcinoma cells depends on
      carcinoembryonic antigen (CEACAM5) expression.
AB  - It was shown that CEACAM5 can mediate cell-cell adhesion through homotypic and
      heterotypic interactions; however, its role in the expression of the malignant
      phenotype remains obscure. To study whether the formation of both primary tumors
      and metastases is directly related to the presence or absence of CEACAM5, we
      applied the antisense RNA strategy. By transfecting human CX-1.1 colon carcinoma
      cells with CEACAM5 antisense-expressing vector or with the vector itself, cell
      variants with a highly decreased expression of CEACAM5 were obtained. Profound
      differences in proliferative abilities among parental and obtained subclones of
      CX-1.1 cells were revealed when cells were implanted subcutaneously into nude
      mice. In contrast to their highly tumorigenic parental CX-1.1 cells (with high
      expression of membrane-bound and secreted CEACAM5), two subclones (3E and AS6Q)
      with substantially decreased expression of membrane-bound and secreted CEA showed
      a considerably diminished growth rate. Even more striking results were obtained
      with AS8Q cells, producing a residual amount of this glycoprotein. However, 3B
      cells (producing a large amount of secreted CEACAM5) did not differ significantly
      in their tumorigenic properties from CX-1.1 cells. Our experiments performed in
      nu/nu mice suggest that CEACAM5 supports the growth of primary tumors, but is not
      involved in the formation of metastases by colon cancer cells.

PMID- 12813581
TI  - Regulation of cell function by Rho GTPases.
AB  - Small GTPases of the Rho family regulate a wide variety of cell functions. In
      this review, we briefly describe the biological activities of Rho GTPases. Using
      the Rac-regulated NADPH oxidase as an example, we discuss possible regulatory
      points that might be exploited for drug development. Finally, we explore
      strategies for specific targeting of Rho GTPase-regulated signaling pathways.

PMID- 12813582
TI  - Role of 5-HT6 receptors in memory formation.
AB  - Mice lacking the 5-HT(6) receptor presented neither gross anatomical or
      behavioral abnormalities nor obvious changes in microscopic brain morphology, and
      their performance in rotarod, open field and novel object testing paradigms
      revealed no differences compared with wild-type animals. Nevertheless, an
      association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's
      disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide
      decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in
      the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04
      6790 improved learning consolidation in an autoshaping task, while mCPP,
      scopolamine and dizocilpine decreased performance. The effect induced by
      scopolamine or dizocilpine, but not that induced by mCPP, was completely or
      partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT
      facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory
      effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7)
      receptor blockade, the facilitatory effect induced by Ro-04-6790 involved
      specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB
      271046 improved retention in the water maze and produced a significant
      performance improvement in aged rats in an operant-delayed alternation task. A
      series of Ro-04-6790 analogues that penetrate the brain and specifically bind to
      5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive
      avoidance learning test. Collectively, these data provide further support to the
      notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in
      memory formation under normal and dysfunctional memory conditions.

PMID- 12813583
TI  - The uPA/uPA receptor system as a target for tumor therapy.
AB  - Invasiveness of a variety of tumors depends on the regulated expression of
      proteolytic enzymes that degrade the surrounding extracellular matrix and
      dissociate cell-cell and/or cell-matrix attachments. The tumor cell surface
      associated urokinase-type plasminogen activator (uPA) system plays an especially
      important role in tumor cell invasion and metastasis. It consists of the serine
      protease uPA, its membrane-bound receptor (uPAR, CD87) and one of the natural
      inhibitors PAI-1 or PAI-2. There are strong indications based on animal
      experiments that interference with this system by inhibiting the enzymatic
      activity of uPA and/or antagonizing its binding to the receptor is of therapeutic
      relevance. With the recent solution of various X-ray structures of uPA/inhibitor
      complexes, structural information is available for optimizing existing lead
      compounds in their affinity and selectivity for uPA. Furthermore, peptide
      compounds capable of mimicking the structural epitope of uPA responsible for
      binding to the receptor efficiently antagonize this recognition process. Thus,
      both approaches prove to be well suited for the design of highly promising drugs
      in human medicine.

PMID- 12813584
TI  - Applications of aquaporin inhibitors.
AB  - The aquaporins are a family of small, integral membrane proteins that function as
      plasma membrane transporters of water and in some cases small polar solutes such
      as glycerol. There are at least 10 distinct aquaporins in mammals with specific
      patterns of expression in epithelial, endothelial and other tissues. Recent
      studies in aquaporin-null mice have indicated key roles for certain aquaporins in
      the urinary concentrating mechanism, fluid secretion by glands, brain swelling,
      skin moisture, hearing and vision, and gastrointestinal absorption. The only
      known inhibitors of some aquaporins are mercurial sulfhydryl-reactive compounds,
      which are too toxic and nonspecific for use in vivo. Small-molecule or peptide
      aquaporin blockers have potential applications in the treatment of disorders of
      fluid/pressure homeostasis such as heart failure, hypertension, brain swelling
      and glaucoma.

PMID- 12813585
TI  - Molecule of the month. T-20.

PMID- 12813586
TI  - New therapeutic approaches in rheumatology.
AB  - This year's European League Against Rheumatism meeting, held in Prague, June
      1316, 2001, was attended by approximately 8,200 registered scientists and
      physicians. The meeting covered a broad spectrum of topics on rheumatic diseases,
      including pathogenesis, diagnostics and treatment. New therapeutic approaches to
      systemic diseases were the highlight of this congress.

PMID- 12813587
TI  - Stiff competition expected in ED market.
AB  - At the British Association of Urological Surgeons Annual Meeting, held June 2529,
      2001, in Dublin, Ireland, participants gathered to absorb the newest information
      regarding treatment strategies, as well as the latest procedures and new
      developments in equipment.

PMID- 12813588
TI  - Odyssey toward a healthier world.
AB  - The 22nd International Congress of Chemotherapy was held in Amsterdam, the
      Netherlands, July 14, 2001. The congress attracted participants from around the
      world and covered a broad spectrum of work on microbial infections and cancer,
      their treatment by antiinfective drugs and their prevention by vaccination. A
      theme of the congress was "Compassion and Science," and this was picked up in a
      fascinating albeit slightly controversial symposium on "Health, Human Rights and
      Infection." There were several well-attended plenary lectures on topical
      subjects, including prions and variant Creutzfeldt-Jakob disease and on a
      possible link between autism and infection.

PMID- 12813589
TI  - Role of MAPK in cerebral vasospasm.
AB  - Cerebral vasospasm is the major cause of mortality and morbidity in patients of
      subarachnoid hemorrhage. Despite intensive studies during the past five decades,
      the signaling pathways in cerebral arteries that lead to the pathological
      contraction remain elusive. The complex nature of cerebral vasospasm requires a
      complex signaling pathway or a group of pathways that may need to interact to
      initiate and maintain vasospasm. This review explores the possibility that
      mitogen-activated protein kinase is the elusive signaling pathway responsible for
      cerebral vasospasm.

PMID- 12813590
TI  - Pathophysiology in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a distressing condition that impairs quality of
      life, and it deserves to be treated. It also has a large economic impact on
      healthcare utilization and absenteeism. IBS is a disorder in which three major
      mechanisms interact: altered gastrointestinal motility, increased sensory
      function of the intestine and psychosocial factors. The role of prior infection
      in the development of IBS is the subject of ongoing study. This article focuses
      on pathophysiological mechanisms, including the potential roles of mucosal
      changes and neurobiology in the development of IBS. Novel pharmacological agents
      are being developed to target neural mediators of IBS; they appear promising, and
      their role in clinical practice will be clarified with regulatory approval and
      clinical use.

PMID- 12813591
TI  - Molecule of the month. Rosuvastatin calcium.

PMID- 12813592
TI  - New insights into pathophysiological mechanisms and treatment modalities.
AB  - At the 3(rd) International Glaucoma Symposium, held in Prague, Czech Republic,
      March 2125, 2001, research scientists, eye care specialists and industry
      professionals gathered from all over the globe to exchange information regarding
      current knowledge of the pathophysiological mechanisms of glaucoma as well as the
      newest treatment modalities.

PMID- 12813593
TI  - Coping with the rising tide of resistance to antimicrobial agents.
AB  - The 11th European Congress of Clinical Microbiology and Infectious Diseases was
      held in Istanbul, Turkey, from April 2nd to April 4th, 2001. The meeting was
      attended by approximately 4,500 people. Sessions were well attended and included
      a number of workshops, keynote lectures, symposia, free papers and posters. As at
      many chemotherapy meetings in recent years, a major topic was the continuing
      growth of resistance among all microbes to antimicrobial agents, and this is the
      topic highlighted in this report.

PMID- 12813594
TI  - Clinical transplantation: optimizing immunosuppressive treatment without
      compromise.
AB  - Transplant 2001, the second joint meeting of the American Society of
      Transplantation and the American Society of Transplant Surgeons, was held from
      May 13 to 16, 2001, in Chicago, Illinois, U.S.A. The congress highlighted the
      constantly improving outcomes of organ transplantation. Incidence of rejection is
      under 15% for most transplants as a result of the availability of various
      immunosuppressants, which in turn permit an expanding number of treatment
      combinations as well as treatments increasingly tailored to the condition and
      needs of each patient.

PMID- 12813595
TI  - Hepatitis B virus transcription and replication.
AB  - Hepatitis B virus (HBV) replicates by the reverse transcription of the 3.5-kb
      viral pregenomic RNA. Therefore, the regulation of the transcription of the
      pregenomic RNA is a critical step in the viral life cycle. Various ubiquitous and
      liver-enriched transcription factors have been shown to modulate the level of RNA
      synthesis from the core promoter. The nuclear hormone receptors HNF4 and RXRalpha
      plus PPARalpha appear to have a critical role in governing pregenomic RNA
      synthesis from the core promoter in cell culture and probably represent a major
      determinant governing the hepatotropism of this virus. The level of 3.5-kb HBV
      RNA synthesis is approximately proportional to the level of viral replication in
      cell culture; however, this is not the case in the liver of HBV transgenic mice.
      Directly modulating the levels or activities of specific transcription factors
      known to regulate HBV transcription in cell culture can increase viral
      replication in HBV transgenic mice without greatly changing the levels of HBV
      transcripts. Various immune stimuli that alter transcription factor activities
      involved in regulating viral RNA synthesis can negatively affect viral
      replication without affecting HBV transcription. These observations suggest that
      in vivo very subtle changes in HBV transcription may contribute to large
      alterations, either negative or positive, in viral replication. Investigation of
      transcription factor-null HBV transgenic mice under various physiological
      conditions will be required to establish the putative role of specific
      transcription factors in regulating viral replication in vivo.

PMID- 12813596
TI  - The nociceptin receptor as a potential target in drug design.
AB  - There are now four types of opioid receptors. The new designations OP(1), OP(2)
      and OP(3) correspond, respectively, to the classic delta-, kappa- and micro
      nomenclature. OP(4) was previously known as ORL(1), the receptor for the
      endogenous heptadecapeptide nociceptin/orphanin FQ. Although the cellular effects
      of nociceptin resemble those of conventional OP(1), OP(2), and OP(3) opioid
      agonists, its effects on nociceptive processes are quite different. Nociceptin
      produces spinal analgesia but appears to antagonize the effects of opioids.
      Following the recent synthesis of the nonpeptide OP(4) agonist Ro-64-6198 by
      Hoffmann-La Roche and the nonpeptide OP(4) antagonist J-113397 by Banyu, the
      nociceptin-OP(4) system now represents a viable and intriguing new target for
      drug design. OP(4) agonists may be of use in the management of neuropathic pain,
      anxiety, anorexia, epilepsy, drug dependence, male impotence, hypertension,
      cerebral ischemia and neurogenic bladder. They may also serve as novel diuretics
      and to help to reduce gastrointestinal motility. OP(4) antagonists may be of use
      as general analgesics and in the improvement of memory function. This review
      covers the recent exciting progress in this field, compares the actions of OP(4)
      agonists and antagonists with those of classic opioids, and seeks to predict some
      of the untoward effects that may be seen with such drugs.

PMID- 12813597
TI  - Inhibition of alpha4 integrin to protect the brain against ischemic injury.
AB  - The potential use of anti-alpha4 antibody presents an attractive approach to the
      treatment of stroke for a number of reasons: firstly, access to the site of
      action; alpha(4) is expressed on circulating leukocytes, permitting efficacy with
      systemic administration and negating the requirement for passage across the blood
      brain barrier, an important consideration for neuroprotective and neurotrophic
      agents and other antiinflammatory approaches such as chemokine inhibitors.
      Pharmacokinetic studies in the rat have demonstrated a maintained pharmacological
      action of alpha(4) antibody for up to 72 hours after a single intravenous dose
      using leukocytosis as a surrogate marker for activity. Finally, the ubiquitous
      pattern of alpha(4) expression on different leukocyte subsets makes it an
      attractive target to combat the early and late inflammatory responses to brain
      injury.

PMID- 12813598
TI  - Herbal preparations as a source of hepatoprotective agents.
AB  - Mono- and polyherbal preparations with potent antihepatotoxic activity in various
      liver disorders, made from traditionally used herbs with proven efficacy, have
      been described. More than 700 mono- and polyherbal preparations in the form of
      decoction, tincture, tablets and capsules from more than 100 plants are in
      clinical use. Some of the herbs--such as Silybum marianum, Picrorhiza kurroa,
      Andrographis paniculata and Glycyrrhizae radix--are very common in most of the
      polyherbal preparations. This review covers the preparations of widely used herbs
      such as S. marianum, Schisandra chinensis, Phyllanthus amarus, P. kurroa, A.
      paniculata, G. radix, Lycium chinense and Cochlospermum tinctorium as
      hepatoprotectants and includes the mode of action of these preparations. Some
      polyherbal preparations such as Livex, HD-03, Hepatomed and Hepatoguard with
      proven efficacy are also described in this review.

PMID- 12813599
TI  - Making advances - but not too quickly and not too many.
AB  - The World Congress of Neurology is one of the major international neurology
      conferences, and this year's meeting, held June 1722, brought almost 5,000
      delegates to London from all corners of the globe. At the opening address,
      President of the World Federation of Neurology James Toole called on neurologists
      to use the greatly improved means of communication to improve society.

PMID- 12813600
TI  - New drug targets in inflammation and immunomodulation.
AB  - The organizers once again achieved the feat of providing a program transcending
      the biology and medicinal chemistry of inflammatory diseases. The speakers
      presented a vast array of topical--often previously unpublished--data and most
      presentations were followed by enlightening, well-informed discussions. The two
      topics chosen highlight the number of new molecular targets being successfully
      pursued in attempts to develop effective new antiinflammatory agents. It is
      interesting to reflect that none of the talks, with the exception of the
      discussion of receptor operated calcium channels, described programs employing
      targets identified from the application of genomics. When the next meeting in
      this series is held it would seem probable that several talks will redress the
      balance.

PMID- 12813601
TI  - Irritable bowel syndrome in primary care: the patients' and doctors' views on
      symptoms, etiology and management.
AB  - BACKGROUND: To facilitate the development of clinical guidelines and to direct
      future irritable bowel syndrome (IBS) research, insight into the perceptions of
      patients and general practitioners (GPs) regarding IBS is required. OBJECTIVES:
      To compare patients' and GPs' views on the symptomatology, etiology and treatment
      of IBS. METHODS: One hundred forty-two IBS patients and 100 GPs were requested to
      complete a structured questionnaire. RESULTS: The response rates of the patients
      and GPs were 80% and 47%, respectively. Abdominal pain and bloating were
      considered to be the most bothersome symptoms in IBS, by both patients and GPs.
      Although all patients were diagnosed by their GP as having IBS, and 62% met the
      Manning criteria, only 18% fulfilled the Rome II criteria for IBS. Patients
      consider food intolerance and GPs regard lack of fibre as the main etiologic
      dietary factor. Many IBS patients expect a diagnostic work-up, but GPs generally
      restrict this to elderly patients. GPs start IBS management with dietary advice
      (94%), counselling (77%) and drug therapy (55%). Patients expect reassurance
      (47%) and drug treatment (37%), but dietary interventions are less appreciated
      (9%). CONCLUSIONS: Patients and GPs have different perceptions of the efficacy of
      diagnostic and dietary interventions in IBS. GPs should explore the patients
      expectations and incorporate these in their approach to IBS patients.

PMID- 12813602
TI  - Clostridium difficile-associated diarrhea: predictors of severity in patients
      presenting to the emergency department.
AB  - OBJECTIVE: Experiences with Clostridium difficile-associated diarrhea (CDAD) were
      reviewed to determine predictors of severity in patients presenting from the
      community. METHODS: All patients admitted to two hospitals over 4.5 years with a
      primary diagnosis of CDAD were reviewed. Patients requiring a hospital stay of
      greater than 14 days, colectomy, intensive care unit admission or who died were
      classified as 'severe CDAD' and compared with the remainder of the patients
      (termed 'mild CDAD'). RESULTS: One hundred fifty-three patients (mean age 63.4+/
      20.5 years, range 21 to 93, 64.7% female) were reviewed. Forty-four per cent of
      the patients had community-acquired CDAD, and the remainder had hospital-acquired
      disease. There were 44/153 (28.8%) patients with severe CDAD, of which 10/153
      (6.5%) died. The severe group had more patients over 70 years old (75% versus 43%
      in the mild group, OR 3.09, CI 1.81-8.63, P<0.001) and had more comorbid disease
      (median two major organ systems affected [range zero to five] versus one [range
      zero to four] in the mild group, OR 1.52, CI 1.27-2.65, P<0.05). Patients with
      recurrent CDAD were more likely to have severe CDAD (12/44 versus 10/109 in the
      mild group, OR 4.10, CI 1.47-9.40, P<0.01). CONCLUSION: Age over 70 years,
      comorbid illness and CDAD recurrence are significant risk factors for severe
      disease and a poor outcome in patients admitted to hospital for CDAD.

PMID- 12813603
TI  - Synchronous epithelioid stromal tumour and lipoma in the stomach.
AB  - An 82-year-old man presented with upper gastrointestinal bleeding. A polypoid
      lesion of the distal stomach with focal ulceration was seen at endoscopy. This
      was treated by a partial gastrectomy. The resected stomach contained two separate
      tumours near the pylorus: a gastrointestinal stromal tumour (GIST) and an
      adjacent lipoma. The literature includes case reports of synchronously occurring
      GIST and adenocarcinoma, GIST and mucosa-associated lymphoid tissue lymphoma and
      GIST and carcinoid tumour. Herein is the first case report of two distinct
      mesenchymal tumors coexisting in the stomach.

PMID- 12813604
TI  - Optical biopsy using tissue spectroscopy and optical coherence tomography.
AB  - 'Optical biopsy' or 'optical diagnostics' is a technique whereby light energy is
      used to obtain information about the structure and function of tissues without
      disrupting them. In fluorescence spectroscopy, light energy (usually provided by
      a laser) is used to excite tissues and the resulting fluorescence provides
      information about the target tissue. Its major gastrointestinal application has
      been in the evaluation of colonic polyps, in which it can reliably distinguish
      malignant from benign lesions. Optical coherence tomography (OCT) has been used
      in the investigation of Barrett's epithelium (and dysplasia), although a variety
      of other applications are feasible. For example, OCT could assist in the
      identification and staging of mucosal and submucosal neoplasms, the grading of
      inflammation in the stomach and intestine, the diagnosis of biliary tumours and
      the assessment of villous architecture. OCT differs from endoscopic ultrasound, a
      complementary modality, in that it has a much higher resolution but lesser depth
      of penetration. The images correlate with the histopathological appearance of
      tissues, and the addition of Doppler methods may enable it to evaluate the
      vascularity of tumours and the amount of blood flow in varices. Refinements in
      these new optical techniques will likely make them valuable in clinical practice,
      although their specific roles have yet to be determined.

PMID- 12813605
TI  - Acute recurrent pancreatitis.
AB  - History, physical examination, simple laboratory and radiological tests, and
      endoscopic retrograde cholangiopancreatography (ERCP) are able to establish the
      cause of recurrent acute pancreatitis in 70% to 90% of patients. Dysfunction of
      the biliary and/or pancreatic sphincter, as identified by sphincter of Oddi
      manometry, accounts for the majority of the remaining cases. The diagnosis may be
      missed if the pancreatic sphincter is not evaluated. Pancreas divisum is a
      prevalent congenital abnormality that is usually innocuous but can lead to
      recurrent attacks of acute pancreatitis or abdominal pain. In select cases,
      endoscopic sphincterotomy of the minor papilla can provide relief of symptoms and
      prevent further attacks. A small proportion of patients with idiopathic
      pancreatitis have tiny stones in the common bile duct (microlithiasis). Crystals
      can be visualized during microscopic analysis of bile that is aspirated at the
      time of ERCP. Neoplasia is a rare cause of pancreatitis, and the diagnosis can
      usually be established by computerized tomography or ERCP. A wide variety of
      medications can also cause recurrent pancreatitis. ERCP, sphincter of Oddi
      manometry, and microscopy of aspirated bile should be undertaken in patients with
      recurrent pancreatitis in whom the diagnosis is not obvious.

PMID- 12813606
TI  - The Canadian Association of Gastroenterology Research Committee report: continued
      commitment to promoting excellence in gastrointestinal related research.

PMID- 12813607
TI  - Fetal memories.

PMID- 12813608
TI  - Recipes.

PMID- 12813609
TI  - Taking the measure of clinical care.

PMID- 12813610
TI  - Outcomes after coronary artery bypass graft surgery in Canada: 1992/93 to
      2000/01.
AB  - BACKGROUND: The authors have previously reported on Canada-wide outcomes of
      coronary artery bypass graft (CABG) surgery for 1992/93 through 1995/96.
      OBJECTIVE: To provide an updated Canada-wide CABG surgery outcome report with
      outcome data organized by province and by year for 1992/93 through 2000/01.
      METHODS: Hospital discharge abstract data were obtained from the Canadian
      Institute for Health Information and were used to identify all patients who
      underwent isolated CABG surgery in eight provinces from fiscal year 1992/93
      through 2000/01. Crude data from Quebec hospitals were available for calendar
      years 1998 and 1999. Logistic regression modelling was used to calculate risk
      adjusted in-hospital mortality rates by year and province. RESULTS: Patients
      undergoing CABG surgery in the later years studied were on average older and had
      more comorbidities than did patients undergoing this surgery in earlier years.
      Despite increasing case complexity, risk-adjusted mortality rates decreased
      significantly from 3.5% (95% CI 3.2% to 3.8%) to 2.0% (95% CI 1.8% to 2.3%). Risk
      adjusted mortality rates varied between provinces. Provincial risk-adjusted
      mortality rates ranged from 2.0% to 3.3%. However, all provinces studied had
      either persistently low mortality rates (Nova Scotia) or declining mortality
      rates across years studied, such that all provinces achieved risk-adjusted
      mortality rates of 2.7% or lower in 2000/01. CONCLUSIONS: This evaluation of
      Canadian CABG surgery outcomes demonstrates a pattern of either steadily
      improving or persistently favourable provincial in-hospital mortality rates after
      isolated CABG surgery. These favourable provincial outcome trends have been
      achieved despite an accompanying increase in the average case complexity of
      patients undergoing CABG in Canada.

PMID- 12813611
TI  - In-hospital outcomes after percutaneous coronary intervention in Canada: 1992/93
      to 2000/01.
AB  - BACKGROUND: Despite existing research on outcomes of cardiac care in Canada,
      little is known about Canada-wide trends and interprovincial differences in
      outcomes after percutaneous coronary intervention (PCI). OBJECTIVES: To examine
      Canadian trends in rates of in-hospital mortality and same-admission coronary
      artery bypass grafting (CABG) after PCI and to compare provincial risk-adjusted
      in-hospital death and same-admission CABG rates. METHODS: Hospital discharge
      abstract data were obtained from the Canadian Institute for Health Information
      and were used to identify cohorts of patients who underwent PCI in eight
      provinces in fiscal years 1992/93 through 2000/01. Crude data from Quebec
      hospitals were available for calendar years 1998 and 1999. Logistic regression
      modelling was used to calculate risk-adjusted in-hospital death and same
      admission CABG rates by year and province. RESULTS: A total of 127,103 PCI cases
      performed in 23 hospitals across eight provinces were examined, with an overall
      unadjusted death rate of 1.4% and an overall unadjusted CABG rate of 1.6%. A
      national trend of stable in-hospital mortality rates was observed with a risk
      adjusted death rate of 1.4% in 1992/93 versus 1.4% in 2000/01. An overall decline
      was seen in rates of same-admission CABG with a risk-adjusted rate of 2.7% in
      1992/93 versus 0.9% in 2000/01 (relative decrease 67%, P<0.01). New Brunswick,
      Manitoba and British Columbia achieved overall declines in risk-adjusted death
      rates over the study period, while the other provinces experienced a slight
      increase (Newfoundland, Nova Scotia, Ontario, Alberta and Saskatchewan). All
      provinces displayed a similar decline in risk-adjusted same-admission CABG rates
      post-PCI. INTERPRETATION: Risk-adjusted rates of in-hospital death after PCI in
      Canada have remained stable over nine years, while risk-adjusted rates of same
      admission CABG have decreased. The presence of interprovincial differences in
      risk-adjusted outcomes raises the possibility of variable quality of care for
      patients undergoing PCI across the Canadian provinces.

PMID- 12813612
TI  - Application of the 1998 Canadian cholesterol guidelines to a military population:
      health benefits and cost effectiveness of improved cholesterol management.
AB  - OBJECTIVE: To determine whether statins are underprescribed in the Canadian
      military. The cost effectiveness of statin therapy in patients identified by the
      1998 Canadian cholesterol interim guidelines was also explored. METHODS: Charts
      of 1424 Canadian military personnel (age 45 or older) were reviewed at 11
      Canadian bases. Risk factors and cholesterol values were used to identify drug
      therapy candidates. Cost effectiveness ratios and health benefits in terms of
      years of life saved for statin therapy were estimated for the candidates using a
      validated cardiovascular disease life expectancy model. RESULTS: Of the 1313
      personnel not on lipid lowering medication, 172 were identified as drug therapy
      candidates. An average of 2.89 years of life saved was forecast for the
      identified personnel, at an average cost of less than 10,000 dollars per year of
      life saved. CONCLUSIONS: The health benefits of statin therapy in this population
      are substantial and the cost effectiveness is acceptable. Statin therapy warrants
      greater attention as a preventive strategy for coronary artery disease.

PMID- 12813614
TI  - Functional testing after coronary artery bypass graft surgery: a meta-analysis.
AB  - BACKGROUND: A number of studies have examined the diagnostic abilities of various
      functional tests to assess graft stenosis or the progression of coronary artery
      disease after coronary artery bypass graft (CABG) surgery. However, a meta
      analysis of these studies has not been performed. OBJECTIVES: To pool the results
      of studies examining the diagnostic abilities of exercise treadmill testing
      (ETT), stress myocardial perfusion imaging and stress echocardiography to predict
      graft stenosis or progression of disease in the native circulation post-CABG.
      METHODS: A MEDLINE search was conducted to identify studies examining post-CABG
      functional testing for the diagnosis of graft stenosis or progression of native
      disease. Sensitivities and specificities of these studies were pooled, and
      predictive values and likelihood ratios were calculated. RESULTS: A pooled
      analysis demonstrates that for the identification of graft stenosis or
      progression of native disease, ETT alone has a sensitivity of 45% (95% CI 36% to
      54%) and a specificity of 82% (95% CI 68% to 95%). The use of stress myocardial
      perfusion imaging increased the sensitivity to 68% (95% CI 51% to 86%) and
      specificity to 84% (95% CI 78% to 91%). The use of stress echocardiography also
      resulted in an increased sensitivity of 86% (95% CI 78% to 94%) and specificity
      of 90% (95% CI 84% to 95%). CONCLUSION: If post-CABG functional testing is
      performed, stress ventricular imaging is superior to ETT alone for the diagnosis
      of graft stenosis or progression of disease in the native vessels.

PMID- 12813613
TI  - Acute thrombocytopenia associated with eptifibatide therapy.
AB  - BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptor blockade improves
      clinical outcomes in percutaneous coronary interventions and in acute coronary
      syndromes. Thrombocytopenia is a serious complication well described with the use
      of the prototype GPIIb/IIIa inhibitor abciximab. Its association with other
      agents of this class has been underemphasized. OBJECTIVES: To determine the
      incidence of thrombocytopenia in a cohort of patients treated with eptifibatide
      at a tertiary cardiac centre. PATIENTS AND METHODS: Chart review of consecutive
      patients treated with eptifibatide at the study institution. RESULTS: There were
      four (1.3%) cases of acute thrombocytopenia (platelet count less than 100 x
      10(9)/L) among 305 patients reviewed. One patient had been previously exposed to
      eptifibatide. The other three patients are described. In each case, platelet
      counts declined within 6 h of receiving eptifibatide. Recovery of platelet counts
      was noted within 6 to 30 h after withdrawal of eptifibatide. No patient suffered
      an adverse clinical event related to thrombocytopenia. CONCLUSIONS: It is
      important to monitor platelet counts closely after initiation of GPIIb/IIIa
      inhibitor therapy, not only for abciximab, but also for small molecule inhibitors
      such as eptifibatide. Monitoring of platelet counts at 2 to 6 h and 24 h will
      detect most cases of acute thrombocytopenia. Adverse events may be prevented by
      prompt discontinuation of GPIIb/IIIa inhibitor therapy.

PMID- 12813615
TI  - Switching from abciximab to eptifibatide for percutaneous coronary interventions:
      a local analysis (SWAP study).
AB  - BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPI) are recommended as adjunctive
      therapy with percutaneous coronary interventions (PCI). Before October 2000,
      abciximab (AB) was the only GPI available at the authors' institution.
      Eptifibatide (EP) was added to the formulary in October 2000 and became the
      preferred agent primarily due to lower cost. OBJECTIVES: To describe the impact
      of switching from AB to EP in the cardiac catheterization laboratory and compare
      clinical and practice-related outcomes of these agents following PCI. METHODS:
      Retrospective chart review was performed on patients who received PCI for all
      indications except as primary therapy for ST-segment elevation myocardial
      infarction. The AB group consisted of all consecutive patients within the six
      months preceding formulary addition of EP in October 2000. A matching number of
      consecutive patients following this date were included in the EP group. RESULTS:
      A total of 160 patients were included (80 per group). Use of adjunctive GPI
      increased from 11% to 25% of PCI within three months of adding EP to the
      formulary (P<0.001). The composite of in-hospital death, myocardial infarction,
      recurrent ischemia and repeat revascularization occurred in 12.5% of EP- and 2.5%
      of AB-treated patients (P<0.025). Minor bleeding was more common in the EP group
      than in the AB group at 8.8% and 2.5%, respectively (not significant). Premature
      GPI discontinuation was significantly more common in the EP group (46.3% versus
      7.5%, P<0.001). The mean +/- SD length of stay post-PCI was 44.4+/-51.2 h for EP
      and 25.1+/-12.3 h for AB (P<0.0001). CONCLUSIONS: Adjunctive GPI usage more than
      doubled following the introduction of EP to the formulary. The present results
      suggest that EP may be associated with inferior clinical outcomes compared with
      AB for PCI patients.

PMID- 12813616
TI  - Cardiovascular adverse effects of herbal medicines: a systematic review of the
      recent literature.
AB  - Herbal medicines are popular but health care professionals often feel uncertain
      about their risks. This article summarizes recent evidence regarding the serious
      or potentially serious cardiovascular adverse effects of herbal medicines. Five
      electronic literature databases were searched. The evidence found was mostly
      anecdotal. Case reports and case series indicate that life-threatening adverse
      effects of herbal medicines occur. Potentially serious adverse effects are
      arrhythmias, arteritis, cardiac glycosides overdose, chest pain, congestive heart
      failure, hypertension, hypotension, myocardial infarction, over-anticoagulation,
      pericarditis and death. The problems relate to toxic herbal ingredients,
      adulteration and contamination of herbal medicinal products, and herb-drug
      interactions. Herbal medicines that have been implicated repeatedly include
      aconite, ephedra and licorice. Because of the anecdotal nature of the evidence,
      it is impossible to estimate the incidence of adverse effects. In conclusion,
      herbal medicinal products are regularly associated with serious cardiovascular
      adverse events but the size of this problem cannot be estimated at present.
      Vigilance and research seem to be the best way forward.

PMID- 12813617
TI  - Cardiac rehabilitation and secondary prevention services in Ontario:
      recommendations from a consensus panel.
AB  - The Cardiac Care Network of Ontario Consensus Panel on Cardiac Rehabilitation and
      Secondary Prevention drew on the literature and its own expertise, and surveyed
      existing cardiac rehabilitation and secondary prevention (CR) services in Ontario
      to make recommendations for the delivery of CR services in Ontario. This report,
      which is not an official position paper for the Canadian Cardiovascular Society,
      presents these recommendations. The key recommendations were a regional
      coordination model for the delivery of CR services that would provide CR close to
      home and promote access to CR in groups traditionally underrepresented in CR;
      high quality central data collection; the creation of a provincial CR registry to
      allow future planning, coordination, monitoring and evaluation of CR services in
      Ontario; and the establishment of specific CR program funding from the Ontario
      Ministry of Health and Long Term Care.

PMID- 12813618
TI  - Primary cardiac sarcoma involving the pulmonary artery and valve.
AB  - Primary pulmonary artery neoplasms are rare and lethal. Those involving the
      pulmonary valve are even rarer with only a few reported cases in the literature.
      The poor prognosis of these neoplasms, despite attempted multimodal therapy, is
      largely related to delay and difficulty in diagnosis. The case of a 53-year-old
      woman is described who within one month of suddenly developing shortness of
      breath was found to have a mass arising from the pulmonary valve and extending
      through the pulmonary vasculature, requiring extensive surgical resection. She
      died two weeks postoperatively. The morphological findings of this primary
      pulmonary artery sarcoma are presented. Diagnosis, treatment, prognosis and
      literature are reviewed, and consideration of this tumour in the differential
      diagnosis of other pulmonary diseases is emphasized.

PMID- 12813619
TI  - A cardiovascular atlas for Canada.

PMID- 12813620
TI  - Angiography of hepatic vascular malformations associated with hereditary
      hemorrhagic telangiectasia.
AB  - PURPOSE: To describe the angiographic features of hepatic involvement in
      hereditary hemorrhagic telangiectasia (HHT), particularly the presence of
      portovenous shunts. METHODS: We reviewed the angiographic findings of seven
      patients with HHT. The patients comprised three women and four men with a mean
      age of 51 years. RESULTS: Intrahepatic telangiectasias were found in all seven
      patients and shunts between three vascular channels were found in six of seven
      patients. In the four patients who had portovenous shunts combined with
      arterioportal shunts, the portovenous shunts were large. Three patients had no
      portovenous shunts. Two of these patients had arteriovenous shunts, and one had
      no shunt. The mean age (69 years) of the patients with portovenous shunts was
      older than those without portovenous shunts (26 years). CONCLUSIONS: Hepatic
      vascular lesions in HHT are varied, ranging from telangiectasias to large shunts
      between three vascular channels. In an advanced stage of involvement, large
      portovenous shunts are present.

PMID- 12813622
TI  - Cysteinyl leukotrienes in porcine acute allergic airway reactions: bronchial and
      vascular effects.
AB  - OBJECTIVE AND DESIGN: The role of cysteinyl leukotrienes (cysLTs) in the acute
      allergic airway reaction in the pig was investigated, with focus on the effects
      on the bronchial circulation, and compared with histamine-induced effects.
      MATERIAL: 31 barrier-bred pigs were used, of which 24 pigs were actively
      sensitised to Ascaris suum. METHODS: Leukotriene D(4) (LTD(4)) and histamine were
      injected intravenously (i.v.) and given as an aerosol to non-sensitised pigs.
      Seventeen animals, sensitised to Ascaris suum, were challenged with Ascaris
      antigen aerosol. The effect of MK-571, a CysLT(1)-receptor antagonist, on LTD(4)-
      and allergen-induced responses were investigated. RESULTS: LTD(4) (2 nmol/kg)
      i.v. injection increased the airways resistance (R(aw)) by 46 +/- 20% and reduced
      bronchial vascular conductance (BVC) by 38 +/- 2%. Both these effects were
      blocked by MK-571 (0.1 mg/kg i.v.). Histamine injections (i.v.) in equimolar
      doses caused similar dose-dependent increases in R(aw), (22 +/- 7%) but induced
      vasodilatation and an increase in BVC (22 +/- 8%). Aerosolised LTD(4) (4 nmol/kg)
      caused a decrease in BVC but did not affect R(aw). In sensitised pigs, challenge
      with Ascaris aerosol led to an acute increase in Raw (198 +/- 57%) and increase
      in BVC (62 +/- 35%). MK-571 (0.5 mg/kg i.v.) pre-treatment did not significantly
      affect these responses (n = 9). CONCLUSIONS: LTD(4) causes constriction of the
      pig bronchi and of the bronchial circulation via activation of the CysLT(1)
      receptor and may counteract histamine-induced vasodilatory effects. However, in
      the allergen-induced acute airway response in the pig, cysLTs do not seem to be
      important bronchoconstrictive mediators.

PMID- 12813623
TI  - Microvascular reactivity in experimental diabetes: responses of male and female
      rats.
AB  - OBJECTIVE: To study the influence of sex on the responses of microvessels to
      vasoactive agents in experimental diabetes. MATERIALS: Diabetes was induced by
      alloxan (40 mg/kg, iv) in male and female Wistar rats (8-10-week-old). METHODS:
      Using an image splitter television microscope, mesenteric arteriolar and venular
      diameter changes induced by topically applied vasoactive agents (histamine,
      bradykinin, platelet activating factor-PAF, acetylcholine, sodium nitroprusside,
      noradrenaline and angiotensin II) were examined. RESULTS: Whereas the
      vasoconstrictor response to noradrenaline was equivalent in normal and diabetic
      animals, either female or male rats, an increased vasoconstrictor response to
      angiotensin II was observed in male but not in female diabetic rats in comparison
      with respective controls. Similarly to that observed in males, the dilator
      response of microvessels to topically applied bradykinin, histamine and PAF was
      impaired in female diabetic rats. Whereas reversal of the impaired responses to
      these agents was obtained by acute treatment of diabetic animals with insulin the
      altered responses to angiotensin II observed in male diabetic rats were not
      corrected. Differently from that observed in males, impaired response of
      microvessels to acetylcholine but not to sodium nitroprusside was observed in
      female diestrous diabetic rats; acute insulin treatment corrected it.
      CONCLUSIONS: We conclude that not all the alterations of the microvascular
      reactivity and the correction by insulin are gender dependent in diabetes.

PMID- 12813625
TI  - Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine
      derivative.
AB  - OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new
      antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro
      binding assay of [(3)H] pyrilamine was performed using recombinant human
      histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR
      mice or Hartley guinea pigs. Drugs were administered orally 1 h before
      examinations. Determinations were made of histamine-induced skin reaction, ex
      vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital
      induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen
      induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding
      to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine
      induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and
      0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg
      of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as
      high selectivity for peripheral H(1) receptors as terfenadine and epinastine did,
      which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg,
      TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427
      significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen
      induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may
      have a long-lasting antihistamine activity with minimum sedative side effect and
      suppress acute phase allergic reactions.

PMID- 12813624
TI  - Effect of dehydroleucodine on histamine and serotonin release from mast cells in
      the isolated mouse jejunum.
AB  - OBJECTIVE AND DESIGN: DhL, a lactone isolated from Artemisia douglasiana,
      prevents gastrointestinal damage elicited by necrosis-inducing agents and
      exhibits antiinflammatory action. This work examines the effect of DhL on
      compound 48/80-induced histamine and serotonin release in the isolated mouse
      jejunum, to determine whether DhL inhibits mediator release from mast cells at
      the enteric level. MATERIAL: Thirty jejuna from male Balb-c mice were used for
      the studies. TREATMENT: Samples were incubated sequentially in 9 test tubes
      containing RBS or 10 microg/ml compound 48/80 or 1.6 mmol/l + 10 microg/ml
      compound 48/80 at 37 degrees C for 90 minutes (10 min per tube). METHODS:
      Histamine and serotonin release studies, quantification of granulated mast cells,
      and evaluation of mast cell ultrastructure were carried out. Differences between
      groups were determined using analysis of variance followed by Tukey-Kramer
      multiple comparisons test. RESULTS: Compound 48/80 increased histamine and
      serotonin release by the tissue (141.95 +/- 62.58 pg/mg tissue vs basal 5.45 +/-
      1.04, P<0.01 and 20.04 +/- 2.81 vs basal 9.24 +/- 1.56 ng/ mg tissue, P<0.01,
      respectively), decreased the number of granulated submucosal mast cells (0.077 +/
      0.0035 vs basal 0.14 +/- 0.015, P<0.05), and elicited evident granule
      ultrastructural changes. These effects were reduced by dehydroleucodine (19.51 +/
      7.88, P<0.01; 12.69 +/- 1, P<0.05 and 0.143 +/- 0.014, P<0.05, respectively).
      CONCLUSION: The lactone inhibits compound 48/80-induced histamine and serotonin
      release from mast cells in the isolated mouse jejunum.

PMID- 12813626
TI  - Increased microvascular permeability in the hamster cheek pouch induced by
      oxidized low density lipoprotein (oxLDL) and some fragmented apolipoprotein B
      proteins.
AB  - OBJECTIVE AND DESIGN: Oxidized low-density lipoproteins (oxLDL) and protein
      fractions obtained by size exclusion chromatography of oxLDL were tested for
      vascular permeability effects on topical application to the hamster cheek pouch.
      MATERIALS: The hamster cheek pouch was prepared for intravital microscopy
      observations of macromolecular leakage at post capillary venules (=leaks) with
      FITC-dextran as tracer. TREATMENT: OxLDL (0.1 mg/ml), PAF (platelet activation
      factor, 50-100 nM) and protein fractions of oxLDL (10 microg/ml) were applied
      topically to hamster cheek pouches. RESULTS: Application of oxLDL and PAF
      resulted in reversible increases in the number of leaks. The PAF-antagonist WEB
      2170, L-NAME and a beta(2)-adrenoceptor agonist inhibited (P<0.01) almost
      completely the macromolecular leakage induced with oxLDL or PAF. Protein
      fractions were found to be more effective than unfractionated oxLDL in inducing
      plasma leakage as calculated on mg/ml-basis. CONCLUSION: Hamster oxLDL is a
      potent inducer of macromolecular leakage increase in the hamster cheek pouch
      microcirculation. The principal effect is mediated by PAF-like structures
      produced by the oxidation of the LDL-particle but oxLDL also contains low
      molecular weight proteins that could contribute to the overall vascular
      permeability increasing effect of ox LDL.

PMID- 12813627
TI  - Effects of ibandronate on inflammation in mouse antigen-induced arthritis.
AB  - OBJECTIVE: To investigate the effects of ibandronate, a novel
      aminobisphosphonate, on inflammation as well as leukocyte-endothelial cell
      interaction in mouse antigen-induced arthritis (AiA). MATERIAL AND TREATMENT: 36
      Balb/c mice were subcutaneously injected with 160 microg/kg of ibandronate once
      per day beginning at day 7 until day 13 after induction of AiA. METHODS: The
      severity of arthritis was assessed by changes of the transverse knee joint
      diameter. For the intravital fluorescence microscopy measurements on day 14 after
      AiA induction, the patella tendon was partly resected to visualize the
      intraarticular synovial tissue of the knee joint. The number of rolling and
      adherent leukocytes as well as red blood cell (RBC) velocity and functional
      capillary density (FCD) were quantified in synovial microvessels. Furthermore,
      leukocyte infiltration in the synovium was determined in histological sections
      with an established score. RESULTS: Both fractions of rolling leukocytes (p =
      0.016) as well as number of extravasated leukocytes (p = 0.004) were enhanced in
      control animals treated with ibandronate in comparison to animals which received
      saline. Arthritic animals with and without ibandronate treatment revealed an
      increased FCD (p = 0.006, p = 0.008), enhanced number of rolling ( p = 0.002, p =
      0.001) and adherent leukocytes (p = 0.009, p = 0.007) and greater swelling of the
      left knee joint (p = 0.002, p = 0.001) when compared to control animals. No
      significant differences between arthritic animals and arthritic animals treated
      with ibandronate were found in any of the parameters assessed including leukocyte
      adherence, FCD, histology, and knee joint swelling. CONCLUSION: Ibandronate
      treatment of healthy mice was associated with an enhanced fraction of rolling
      leukocytes and increased numbers of extravasated leukocytes indicating a
      proinflammatory effect on the synovial microcirculation. In animals with a
      preexisting antigen-induced arthritis, however, ibandronate did not induce an
      exacerbation of joint inflammation and leukocyte adherence.

PMID- 12813632
TI  - [Pancreatic cancer--diagnostics and therapy].

PMID- 12813633
TI  - [How much diagnostics in patients with pancreatic cancer?].
AB  - The possibilities which actually exist in order to obtain an earlier diagnosis in
      pancreatic carcinoma, a better differentiation of mass-forming pancreatitis and
      of other pancreatic tumors and an improved staging for reducing unnecessary
      operations are presented and evaluated. Possible relevant hints of the history
      and indicators for diagnostic procedures in view of a pancreatic carcinoma are
      upper abdominal complaints especially in relation to a new developed diabetes
      mellitus and/or unexplained elevations of pancreatic enzymes. The endosonography
      in combination with a target biopsy is of important value as well for the
      diagnosis of pancreatic cancer as for differentiation against a segmental chronic
      pancreatitis. In cases where differentiation is impossible even intraoperatively,
      we recommend the use of intraoperative fine needle biopsy.

PMID- 12813635
TI  - [Intrasurgical diagnostics in the case of suspected pancreatic cancer--the
      cytology].
AB  - A differentiated therapy of chronic pancreatitis and pancreatic carcinoma calls
      for evaluation of the validity of findings. Excisional biopsies, punch biopsies,
      and fine-needle aspiration cytology (FNAC) are the options available for
      intrasurgical confirmation. In 606 prospective cases intrasurgical fine-needle
      aspiration biopsy and cytological assessment were carried out. There were 330
      cases of pancreatic carcinoma and 276 cases of benign diseases of pancreas
      included. The level of sensitivity is 92.4 %, specificity is 99.3 %, predictive
      value of positive results is 99.3 % and of negative results is 91.6 %. FNAC is a
      suitable method for confirmation of pancreatic carcinoma.

PMID- 12813634
TI  - [The value of fluorodeoxyglucose positron emission tomography (FDG-PET) in
      differentiation of pancreatic lesions].
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a
      functional imaging modality that is based on the metabolic activity which is
      higher in most malignant tumors than benign tissues. This short review describes
      the basics of FDG-PET and gives a discussion of its role in differentiation of
      focal pancreatic lesions. The diagnostic accuracy in patients with active
      inflammation or cancer of the pancreas can be improved by dynamic acquisition of
      focal pancreatic lesions.

PMID- 12813637
TI  - [Operative management in the treatment of pancreatic cancer].
AB  - The carcinoma of the pancreas is one of the 10 leading causes of death in the
      Western countries. Because of the resistance of pancreatic cancer against
      radiation and/or chemotherapy surgery is still the only possibility for cure.
      However, about 80 % of patients with the diagnosis of pancreatic cancer are no
      more suitable for curative resection at the time of diagnosis because of local
      tumor infiltration or the presence of distant metastases. This is one reason for
      the unsatisfactory situation in terms of 5-year-survival rate of 3 to 24 %. In
      resectable tumors of the pancreas head the standard Whipple dominates still as
      the surgical method of choice. However, the pylorus preserving Whipple has been
      established as a surgical alternative to the classical Whipple. Other surgical
      procedures like extended or regional pancreatic resections, predominantly done by
      Japanese surgeons seem to fit the concept of radical resection. But compared to
      the classical Whipple or the pylorus preserving Whipple resection there is still
      no clear advantage in terms of long term survival. The prospective European
      multicenter study ESPAC-1 firstly demonstrated a survival advantage for adjuvant
      chemotherapy (5-FU and folic acid) but no gain for radiochemotherapy in the
      treatment of patients with R0 or R1 resected pancreatic cancer in terms of
      prolongation of mean survival (19.7 months vs. 14.0 months).

PMID- 12813636
TI  - [Anesthesiological management of pancreatectomy with curative intention in
      pancreatic carcinoma].
AB  - Pancreatectomy for pancreatic carcinoma makes high demands on the perioperative
      anesthesiologic management of these patients. This survey is centered on
      pathophysiological reflections related to the choice of the anesthesia and
      accompanying therapy, concerning the pathological mechanisms of intra- and
      postoperative complications. The influences of the surgical as well as the
      anesthesiological procedure on the autonomous nervous system and splanchnic blood
      flow, the organo-specific consequences of the resection and the possible
      influences on the immune system are discussed. Recommendations for perioperative
      medical care of these patients are derived from it. Central points are an
      anesthesiologic management adapted to the patient with regard to
      pathophysiological changes caused by surgery, monitoring and therapy of the
      disturbed fluid balance, postoperative intensive care as well as an optimal pain
      treatment.

PMID- 12813638
TI  - [Carcinoma of the pancreas head, papilla Vateri, and cystadenocarcinoma-
      different biologic entities and different results].
AB  - Between 1986-1995 we operated 337 patients with ductal adenocarcinoma of the
      pancreas, 45 cases of carcinoma of the papilla of Vater and 11 patients with
      cystadenocarcinoma of the pancreas. The evaluation of prognostic factors showed
      the influence of lymph node invasion. Furthermore we saw a significant influence
      of lymph- and haemangiosis carcinomatosa, of tumor-grading and tumor-size. The
      carcinoma of the papilla showed a better 5-year survival even in nodal-positive
      patients--this as a result of a different biological behaviour. We think that-
      instead of missing improvement of cure in ductal adenocarcinoma over the past
      decade--there is no place for therapeutic nihilism especially in non-ductal
      cancer, which represents almost 15 % of all pancreatic neoplasms.

PMID- 12813639
TI  - [Late results after operative treatment of biliopancreatic cancer].
AB  - In this paper the late results after operative therapy of biliopancreatic
      carcinomas will be presented. Tumors of this region have many things in common.
      That's why we investigated the 4 tumor entities together. We studied the case
      histories of 434 patients treated between 1981 and 1997. We analysed the in- and
      outpatient data of the "Klinikum der Stadt Gera", documents of the tumor board
      and informations that were obtained from the ambulatory treating physicians. 283
      patients suffered from pancreatic carcinoma, 50 from bile duct carcinoma, 60 from
      gallbladder carcinoma and 41 from carcinoma of the papilla Vateri. The survival
      rates after curative or palliative operative therapy of the 4 tumor entities were
      calculated according to Kaplan-Meier. The rate of curative operations and the 5
      year-survival-rate after curative resection were 32.8% and 19.0%, resp. in
      pancreatic carcinoma, 28.0% and 49.0% in bile duct carcinoma, 26.7% and 50.0% in
      gallbladder carcinoma and 71.0% and 44.0% in carcinoma of the papilla Vateri. Due
      to the higher resection rate the overall results in patients with carcinoma of
      the papilla Vateri were much better than the results in the other analysed
      cancers. Up to now resection is the only way to cure the 4 entities of malignant
      tumors of the biliopancreatic region.

PMID- 12813640
TI  - [Endoscopic biliary drainage in patients with pancreatic cancer].
AB  - Obstructive jaundice is a common clinical sign in patients with pancreatic
      cancer. 52% of all patients with a potentially resectable pancreatic cancer
      suffer from painless obstructive jaundice. There are no prospective studies
      showing a beneficial effect of preoperative drainage in patients with resectable
      pancreatic cancer. Morbidity (53%) and mortality (15%) in patients without
      preoperative biliary drainage are not significantly different from those who had
      endoscopic drainage preoperatively (morbidity 41%; mortality 15%). However, there
      are some logistic reasons for preoperative drainage, especially if surgery is
      delayed. In cases of nonresectable pancreatic cancer endoscopic drainage for
      palliation of obstructive jaundice is the method of choice. The decision between
      metallic and plastic stents for palliation is based on expected survival time and
      quality of life. Implantation of metal stents is the method of choice in patients
      with life expectancy exceeding six months. Scheduled three months exchange of
      plastic stents is recommended to avoid complications. After a six months interval
      about 70% of patients with scheduled exchange are without symptoms, compared to
      about 40% of patients who had exchange of plastic stents on demand. Scheduled
      three months exchange of plastic stents leeds to a patency rate of plastic stents
      comparable to those of metallic stents.

PMID- 12813641
TI  - [Adjuvant treatment of pancreatic cancer].
AB  - The prognosis of pancreatic cancer is poor at any stage. The complete resection
      of the tumour offers the only chance of cure, but 10-25 % of the patients at most
      present with operable disease, and median survival following surgery with
      curative intention is 18 months. Local recurrence is often accompanied or rapidly
      followed by distant metastasis. Studies of postoperative (adjuvant) treatment
      have yielded contradictory results. Combined radiochemotherapy resulted in
      improved survival in a few studies while others failed to demonstrate any
      survival benefit. Intraoperative radiation therapy given in addition to
      percutaneous irradiation may improve local tumour control at best. At present
      only few data support the benefit of adjuvant systemic chemotherapy alone.
      Unfortunately, the recently completed ESPAC-1 study was not very helpful in
      settling this issue due to its problematic design. Therefore, the results of
      ongoing studies of adjuvant chemotherapy are eagerly awaited. These studies have
      also included arms with gemcitabine, the current standard for palliative
      treatment of pancreatic cancer, and will hopefully allow firm conclusions as to
      the role of postoperative chemotherapy.

PMID- 12813642
TI  - [Intraoperative neurolysis of the celiac plexus in patients with unresectable
      pancreatic cancer].
AB  - BACKGROUND: The analgetic treatment of inoperable pancreatic cancer patients is
      of paramount importance. The relative ineffectiveness of pharmacological agents
      has led many investigators to recommend chemical neurolysis of the celiac
      ganglions for pain control. However, the assessment of the results and the
      effectiveness of the block carried out during laparotomy have been unclear.
      PATIENTS AND METHODS: After 41 intraoperative celiac neurolytic blocks pain
      intensity was retrospectively analysed in 38 patients suffering from unresectable
      pancreatic carcinoma. The mean age of the patients was 59 years, the observation
      period after neurolysis ranged to 6 months. All patients underwent definitive
      neurolysis using 50 % ethanol in 0.5 % prilocaine. Immediate and long-term
      efficacy, analgetic consumption and mortality were evaluated at follow-up. The
      calculated parenteral equivalent morphine dosage (mg per day) was evaluated
      before as well as at different time points after treatment as an objective
      parameter to describe pain intensity. RESULTS: 7 to 34 days (at discharge from
      the hospital) after block pain intensity was statistically highly significant
      reduced (p=0.016). Long-term results were obtained from 17 (10 to 12 weeks after
      intervention) and 9 (up to 20 weeks after intervention) patients respectively,
      demonstrating a long-lasting effect of the neurolysis. A statistical analysis was
      not possible because of the small patient 's number. CONCLUSIONS: Intraoperative
      celiac neurolytic block is a safe and effective method of pain treatment in
      patients with unresectable pancreatic carcinoma. However, it alone provides
      complete pain relief until death only in a few cases. Therefore, it should be
      considered as an adjuvant treatment in the analgesic strategy. Combined
      palliative therapy is necessary in most of the cases.

PMID- 12813643
TI  - [The therapy of benign pancreatic tumors].
AB  - A more distinct histopathological classification of pancreatic tumours has been
      developed during the last years. However, up to now the preoperative diagnostic
      tools are not able to predict sufficiently the kind of the tumour, particularly
      the differentiation between benign and malignant. This is the prior condition for
      limited resection procedures like the enucleation. Therefore partial pancreatic
      resection is the treatment of choice even for benign tumours except for small
      insulinomas. These tumours are easy to diagnose, have only a limited potential
      for malignancy and are removed by enucleation. We report on our experience will
      60 benign cases (50 cystic neoplasms, 10 neuroendocrine tumours) during the last
      8.5 years in our institution with the following operative procedures: 2 total
      pancreatectomies, 21 pancreatic head resections, 25 left pancreatectomies, 10
      pancreas segmental resections amd 2 enucleations.

PMID- 12813644
TI  - [Rare tumors of the pancreas].
AB  - From 1984 to 2001, 486 operations were carried out at the surgical clinic in Gera
      for pancreatic neoplasms, including 49 patients with rare neoplasms of the
      pancreas. In 23 patients malignant pancreatic tumors were present (9 solitary
      metastases, 9 endocrine carcinomas, 2 cystadenocarcinomas, 2 schwannomas and one
      non-Hodgkin's lymphoma). In 28 benign lesions a resection of the tumor was
      performed, concerning 8 insulinomas, 8 serous cystadenomas, 3 mucinous
      cystadenomas and 4 rare cystic tumors. A sarcoidosis, an autoimmune pancreatitis
      and a radiation fibrosis were diagnosed in 3 patients operated under the
      suspicion of a malignant pancreatic tumor. By means of own case examples and data
      from the literature these rare entities are described with their diagnostic and
      therapeutic special features.

PMID- 12813645
TI  - [Lesions of the spleen in chronic pancreatitis by thrombophlebetic splenomegaly
      and cyst penetration].
AB  - Chronic pancreatitis leads to changes of nearby organs with possible acute and
      chronic complications including lesions of the spleen. Among 341 patients
      operated upon between January 1981 and June 2002 in the surgical department Gera,
      we found 7 spontaneous spleen ruptures or such after minimal trauma and 4
      pseudocysts, which expanded to the splenic hilus. In all cases splenectomy was
      carried out with resection of the tail of the pancreas with or without drainage
      of the pancreas. 2 patients with a history of splenectomy after minimal trauma
      underwent duodenum-preserving resection of the pancreatic head to Frey, and
      distal pancreatectomy, resp. CONCLUSIONS: Lesions of the spleen belong to the
      rare complications of chronic pancreatitis. With known case history and mostly
      delayed course, the operative concept must be concentrated not only on the
      splenic lesion but also on the therapy of the chronic pancreatitis.

PMID- 12813646
TI  - [Solid-pseudopapillary tumor of the pancreas as differential diagnosis in
      pancreatic tumors of the young].
AB  - AIM: The presentation of solid pseudopapillary tumors of the pancreas (SPTP) with
      examples of our own surgical department. SPTP occur typically in young women or
      in children and are for most of benign behavior. In about 5 % a malignant course
      with occurrence of metastases can develop. METHODS: Diagnosis, morphological and
      histological findings and therapeutic approach are described in three cases. The
      differential diagnosis of other tumors of the pancreas is discussed. FINDINGS:
      Three women (age 21, 33 and 43) with SPTP have been treated in the Department of
      Surgery at the University of Wurzburg between 1997-1999. All tumors were resected
      curatively. No adjuvant treatment was performed. The follow up ranged from 31-56
      months. No relapse of disease or occurrence of metastases were observed. All
      resected specimen revealed the typical character of SPTP with areas of solid
      parts and hemorrhage within the tumor. A panel of immunohistological markers
      (Vimentin, N-Cam, NSE, Chromogranin, Synaptophysin, Ck7, Ck19, Ck20, EMA) and
      expression of receptors were investigated. CONCLUSION: The diagnosis of this rare
      tumor can be made clinically and intraoperatively according to its typical
      morphology and occurrence, predominantly in young women or in children thus
      helping to perform adequate surgical therapy.

PMID- 12813647
TI  - [Evolution of the treatment of pancreatic cancer].
AB  - Cancer of the pancreas was not diagnosed until the nineteenth century, and the
      first surgical attempts were not carried out until the end of that century, and
      then only within the framework of local tumour removal. Already in 1898, however,
      Codivilla described the operative method that is today considered the standard
      operation and which, in the form of partial duodenopancreatectomy, is the most
      commonly performed procedure on the pancreas. Evolutionary change in this area
      represents nothing more than the gradual introduction of minor modifications
      which, however, had no impact on the " heart" of the surgical approach. The
      particular feature of surgical treatment of pancreatic cancer--since 1935 known
      as Whipple's procedure--is the considerable length of time of 80 years that it
      took before it finally found widespread acceptance. Further several decades
      passed until, by the end of the 20th century, recognizable successes were
      reported, for example, a resection rate of 30%, a hospital mortality rate of less
      than 5% in specialized centers, and a reported 5-year survival rate varying from
      1% to 20%. Even after the last 100 years of slow evolution, surgeons have by no
      means conquered cancer of the pancreas, and the low 5-year survival rates,
      together with the recurrences and late metastases prompted Trede in the year 2002
      to remark: "we have to conclude that surgery alone cannot cure pancreatic
      carcinoma".

PMID- 12813648
TI  - [The incurable patient under the guidance of his doctor and relatives].
AB  - Caring for an incurable patient during the last phases of his life belongs to the
      hardest duties of a doctor and requires empathy and sympathy. It is important to
      find the narrow pathway between truth and hope, to take the fear from the
      patient, that he would be left alone, and to preserve always his human dignity.

PMID- 12813649
TI  - [Shared decision making: an approach to strengthening patient participation in
      rehabilitation].
AB  - In this paper, the concept of Shared Decision Making, i. e. the participation of
      the patient regarding the selection of therapeutic goals and treatment options,
      is presented. The degree of patient participation in medical decisions varies
      widely across different models of the physician-patient relationship. According
      to the paternalistic model, the physician knows best what is in the patient's
      interest; patient participation is limited. This model clearly does not take into
      account patients' autonomy and desire for information appropriately. In contrast,
      the informative model claims that values are well-known to the patient while the
      physician's role is restricted to providing him with the necessary information.
      However, the assumption of fixed values may be challenged. Patients expect their
      doctors to be not only technical experts but also caring persons. In the
      interpretive model, the physician's task is to help the patient to identify and
      express his values. In the deliberative model, both physician and patient engage
      in an open discussion about the values the patient could and should pursue. The
      physician is allowed to present his own preferences, and conflicting values are
      discussed explicitly. Thus, the patient is empowered to choose between
      alternative preferences. This model forms the basis of shared decision making,
      which involves at least two participants who engage in a process of both mutual
      information and interactive discussion. Patient participation should result in a
      greater sense of personal control, more satisfaction with treatment, better
      compliance and transfer into the daily routine of disease management and,
      consequently, better outcomes. Although it is largely unknown whether these
      outcomes are achieved, indirect evidence may be gained from systematic reviews
      showing that a favourable physician-patient communication (i. e. allowing
      patients to express their information needs and concerns and to receive both
      information and emotional support) produced better outcomes regarding both mental
      and physical health. There are several barriers to shared decision making. No
      information exists regarding the degree to which physicians are interested in
      shared decision making. While there is ample evidence that patients' needs for
      information are high, patients' wishes for participation seem to vary widely,
      though. Both physicians and patients require the ability to make shared
      decisions. Structural restraints include time and institutional inflexibility. To
      conclude, shared decision making is a promising approach to enhance patient
      participation in rehabilitative care.

PMID- 12813650
TI  - [Prospective payment in medical rehabilitation].
AB  - After introducing DRGs (Diagnosis-Related Groups) in the prospective payment
      system for German hospitals, the use of per-case reimbursement for medical
      rehabilitation as well is being discussed. In particular two systems have already
      been tested internationally. FIM-FRG were especially developed for a prospective
      payment system for inpatient rehabilitation facilities. RUG-III are used for
      reimbursing long-term care in nursing homes and are based on a per-day payment.
      It is recommended to test the FIM-FRG or one of the refined systems in Germany in
      a pilot project.

PMID- 12813651
TI  - [Efficacy of inpatient rehabilitation for chronic back pain in Germany: a
      systematic review 1980-2001].
AB  - BACKGROUND: Chronic back pain has a high personal impact, is frequent and of
      outstanding economical relevance. Analysis of the international literature
      indicates strong or moderate evidence for the effectiveness of multimodal
      multidisciplinary team care of chronic back pain. Our review aims at a complete
      review and critical appraisal of German studies of inpatient medical
      rehabilitation. METHODS: We conducted a systematic search for relevant German
      studies (1/1980 - 6/2001) using electronic data bases, manual search of congress
      abstracts and postal questionnaires of 712 German rehabilitation clinics.
      Relevant studies were categorized according to the recommendation of the Cochrane
      Back Review Group. For all studies, aims, participants, type of intervention,
      evaluation time, main outcomes and results were extracted and tabulated. The
      effect size for 6 central outcome parameters (pain intensity, functional status,
      catastrophizing, depression, vitality, days on sickness leave) were calculated
      using pre-post comparisons and were integrated into short and long term weighted
      means of intra-group effect sizes. RESULTS: 30 studies, both controlled and
      uncontrolled, report a multitude of positive changes with inpatient
      rehabilitation treatment. Improvements included both somatic and psychological
      parameters. However, methodological quality was often poor; only three studies
      fulfilled the criteria for high quality. Comparison of meta analyses of German
      and international studies indicates partly good agreement (e. g. changes in pain
      intensity), partly discrepancies (e. g. functional ability in daily activities).
      Taken together, inpatient rehabilitation treatment for chronic low back pain in
      Germany appears to be of low to moderate efficacy. DISCUSSION AND CONCLUSIONS: In
      the era of evidence based medicine, inpatient rehabilitation has to show its
      usefulness, necessity and efficiency as any other type of health care. For the
      German system of inpatient rehabilitation of chronic back pain available evidence
      is not conclusive, due to a lack of randomised controlled studies. The prevailing
      design of observational cohort studies has severe limitations in proving a causal
      relationship between outcomes and intervention. The international literature
      however provides more valid evidence in favour of the multimodal
      multidisciplinary intervention in chronic back pain. Under the assumption of a
      "class effect" of medical rehabilitation the German data seem to corroborate the
      conclusions drawn from international studies.

PMID- 12813652
TI  - [Fear of progression in patients with cancer, diabetes mellitus and chronic
      arthritis].
AB  - Fear of an increasing disease progression (fear of progression) is among the main
      psychological stresses in patients with cancer, diabetes mellitus (type 1 and
      type 2) and chronic arthritis. The questions the study seeks to answer are: (1)
      Which are the main fears of these patients?, (2) How and in which circumstances
      in life do they occur?, (3) Which are the triggers of the fear? To answer these
      questions, a sample of 65 patients were researched through interviews. The
      results indicate that the predominant fears of cancer patients are the fear of
      dying and the unpredictability of the progression of the disease. Patients with
      chronic arthritis most frequently fear being physically dependent on someone
      else. The most common anxiety of diabetes patients are long-term complications.
      For all three groups of patients job-related fears cause a high amount of
      distress. These results contribute to the development of a standardised fear of
      progression questionnaire.

PMID- 12813653
TI  - [Depression in cardiac patients undergoing rehabilitation--a study for
      investigating the correlations between depression and occupational groups].
AB  - The results of many studies show that physical recovery and social integration of
      cardiac patients are negatively influenced by a persistent depressive disorder.
      For this reason issues of occupational integration should be considered from this
      point of view, too. Correlations between various occupational groups and
      depression were investigated with 907 cardiac patients at the beginning and at
      the end of a follow-up treatment. The results were compared to those for 756
      persons in corresponding age groups from the general population. We found that at
      the beginning of rehabilitation the depression values of the HADS did not show
      any significant differences between the various occupational groups, however,
      their values were significantly higher than those found in the general
      population. During rehabilitation the HADS values decreased significantly. At the
      end of rehabilitation, unskilled and semi-skilled workers had significantly
      higher depression values than skilled workers and persons in higher positions.
      Consequences for medical rehabilitation are discussed.

PMID- 12813654
TI  - [A brief scale for measuring subjective prognosis of gainful employment: findings
      of a study of 4279 statutory pension insurees concerning reliability (Guttman
      scaling) and validity of the scale].
AB  - The psychometric properties of a 3-item scale for the assessment of subjective
      vocational disability were tested in 4279 blue-collar workers. Internal
      consistency of the scale was estimated by Guttman scaling. To evaluate construct
      validity the scale was compared to other measures of vocational ability,
      functional capacity, comorbidity, psychic status, and indicators of occupational
      handicap. The results are highly satisfactory, and the scale can be recommended
      for further use in rehabilitation research. Ongoing research is discussed.

PMID- 12813655
TI  - ["Objectives, setting conditions, differential aspects and evaluation of patient
      education programmes"--working conference of the Bavarian Rehab Research Network,
      RFB, in cooperation with the "Patient Education" Working Group, January 13-14,
      2003 in Wurzburg].

PMID- 12813656
TI  - [Further development of the German DRG system--the position of the German Society
      for Rehabilitation of the Disabled].

PMID- 12813657
TI  - [Is return to work probability diminished by vocational rehabilitation? On
      microeconometric evaluation on the example of the "Sweden Study"].

PMID- 12813658
TI  - [The 106th "Deutsche Arztetag" in Cologne--consequences for the discussion about
      continuing medical education].

PMID- 12813659
TI  - [Assessment and psychotherapeutic options of patients with somatoform disorders
      and a claim for invalidity pensioning].
AB  - Difficulties in the assessment of patients with somatoform disorders and a claim
      for social security benefits or invalidity pensioning pose a considerable
      challenge to the medical community. Within the process of delivering a medical
      expert's opinion, psychiatric and psychological factors often are underestimated.
      There are ample recommendations to apply specific criteria within the medical
      expert's report, but there are no empirical studies confirming that these
      criteria are really used and prognostically valuable. Especially, despite the
      growing numbers of psychosomatic in-patients and the thereby heightened
      socioeconomic importance, there are nearly no catamnestic studies which
      sufficiently evaluate the results of psychotherapy in the specific group of
      patients with somatoform disorders and a pending desire for financial
      compensation alone. The rare available data provides a nearly disastrous
      impression of psychotherapy results in this patient group. This review article
      highlights important problems of this special patient group and provides some
      suggestions concerning the further handling of the addressed issues.

PMID- 12813660
TI  - [Psychosocial burden and subjective experience of melanoma patients in the
      ambulant follow-up].
AB  - INTRODUCTION: The ambulant follow-up is established for early detection of
      metastases thus improving the survival probability of tumor patients. In spite of
      the safety aimed at, follow-up also puts a burden on tumor patients and has
      effects on their quality of life. AIM: To investigate within the scope of follow
      up, to collect data on the psychosocial burden on melanoma patients in relation
      to the predictors (medical factors, psychological variables, sociodemographic
      data) in order to define a "burden-risk patient". METHOD: From June to December
      1997, 615 ambulant melanoma patients were questioned with the aid of the
      Hornheide questionnaire and the German version of the Hospital Anxiety and
      Depression Scale (HADS-D). RESULTS: The leading predictors for a psychosocial
      burden were found to be fear and depression, as well as tumor thickness,
      metastases, year of operation, sex, age, and marital status/household. With the
      aid of these results, a burden-risk patient could be defined: female sex, age
      between 40 and 59 years, divorced or widowed, separately living, with a tumor
      thickness of more than 4 mm, first diagnosis less than 3 years ago and prevailing
      metastases. This risk patient had also a high probability of having significant
      fear and depression values. CONCLUSION: The use of the Hornheide questionnaire
      for identifying the psychosocial burden is suitable to collect the individual
      burdens of the patients in particular and within a short period. In the same way,
      the needs of the patients can be met in particular, and thus his/her quality of
      life can be increased.

PMID- 12813661
TI  - [The Luebeck Interview for Psychosocial Screening (LIPS)--a validation study with
      patients suffering from coronary artery disease].
AB  - Identifying patients in cardiology who are able to benefit from more detailed
      psychosocial diagnostics or interventions is still problematic in every day
      hospital care. Existing psychosocial screening instruments--either self
      evaluation questionnaires and evaluation interviews carried out by doctors--are
      discussed. A new screening instrument for evaluating patients in cardiology is
      presented: The Luebeck Interview for Psychosocial Screening (LIPS). With help of
      LIPS patients are evaluated by their doctor through a short semistructured
      interview referring to the patients' psychosocial situation. Test statistical
      data of the instrument gained through 194 patients are presented. For a subgroup
      of 80 patients the validity for predicting their quality of life six weeks after
      discharge form hospital by psychosocial assessment in hospital is presented. Data
      on reliability and validity of LIPS appear to range from acceptable to good.
      Predicting quality of life by self-report inventories reaches a better fit than a
      prediction by LIPS as an evaluation from the doctor's perspective. The errors of
      the prediction by both methods are highly correlated. Further research on LIPS
      combined with a structured clinical Interview for mental disorders seems to be
      desirable.

PMID- 12813662
TI  - [Personality and donor-recipient relationships of potential donors before living
      donor liver transplantation--diagnostics with the repertory-grid technique].
AB  - BACKGROUND: Living-donor liver transplantation (LDLT) is developing into an
      established therapy for terminal liver diseases in adults. Potential donors are
      faced with the risk of postoperative complications and are subject to a high
      level of psychological pressure and ambivalent feelings. Our assumption is that
      ambivalent feelings before donation are crucially influenced by the personality
      and the quality of the donor-recipient relationship. In highly motivated donors
      we expected a positive description of the recipient and a similarity in the
      characterisation of the donor and recipient. METHODS: 58 potential living donors
      were evaluated between March 2000 and June 2001. On the basis of the clinical
      interview 10 were rated as unsuited for donation. Among those potential donors
      assessed as unsuited, we found a high level of ambivalent feelings. For 50
      potential donors we gained a set of completed psychometric diagnostic
      questionnaires. A Repertory-grid investigation was conducted with a total of 28
      potential donors. Seven of them were not recommended as living donors. The
      relationship between donors and recipients was analysed concerning constructs
      that were most important to the characterisation of the donor or recipient. By
      means of inter-element distances self-concept of donors and donor-recipient
      relation were analysed. RESULTS: Ambivalent candidates who were not recommended
      as living donors tended to describe the recipient negatively (selfish, carping,
      and unable to take criticism) and did not show a similarity in the
      characterisations of self and ideal-self. Whereas the highly motivated candidates
      were marked by a closeness of self and ideal-self concepts. Both groups saw the
      recipient as indifferent. CONCLUSION: Closeness between self and ideal-self
      indicating satisfaction with the decision to donate seems to be one suitable
      criterion to distinguish between highly motivated potential donors on the one
      hand and ambivalent candidates on the other hand. Another criterion appears to be
      a description of the recipient that indicates either a functioning or ill
      functioning communication between donor and recipient with respect to the
      donation.

PMID- 12813663
TI  - [SARS--a permanently current topic].

PMID- 12813664
TI  - [Carcinoma of the lung affects the entire person].

PMID- 12813665
TI  - [A somewhat different view].

PMID- 12813666
TI  - [Severe acute respiratory syndrome (SARS)].
AB  - The severe acute respiratory syndrome (SARS) is a highly infectious respiratory
      disease, to the best of our knowledge caused by a hitherto unknown corona virus.
      The virus has spread from South East Asia to many countries of the world. Three
      case reports of patients from the Prince of Wales Hospital of The Chinese
      University of Hong Kong demonstrate typical clinical courses. Fever, cough, in
      most cases non-productive, myalgia, chills, and rigor are the leading symptoms.
      Leucopenia and thrombocytopenia are the most prominent laboratory parameters,
      increased values for lactatedehydrogenase (LDH) reflect a more severe clinical
      course. Advanced age and coexisting conditions seem to influence the prognosis
      unfavourably. The chest roentgenogram may be normal initially but at a later
      stage progressive consolidations in the majority of peripheral parts of the lung
      are observed, which cannot be differentiated from pneumonias of other origin.
      Even young patients can enter a stage of respiratory compromise rather fast. A
      therapy against the cause of the disease is not known. Empirical therapy with
      ribavirin in combination with high dose corticosteroids have proved successful.
      The disease may progress into respiratory failure comparable with an acute
      respiratory distress syndrome (ARDS). Mortality is around five to ten per cent.
      Stringent hygiene and quarantine measures are mandatory to prevent the further
      spread of this threatening disease.

PMID- 12813667
TI  - [Fine needle aspiration cytology as diagnostic bed-side method for differential
      diagnostics of enlarged peripheral lymph nodes].
AB  - Enlarged lymph nodes are a common diagnosis in clinical practice. The causes are
      varied and both benign or malignant processes might be responsible. Clearly it is
      important to quickly discern whether the origin is malignant or benign. The aim
      of this study was to evaluate the reliability and efficacy of aspiration cytology
      of enlarged lymph nodes. 398 patients with peripheral enlarged lymph nodes, who,
      in the course of a five-year period, were subjected to at least one immediate
      cytologic analysis (bed-side-analysis), were included in the study. For
      comparison the gold standard was defined as either the histological result of a
      corresponding biopsy or the clinical outcome within an observation period of one
      year. Cytology analysis reached a sensitivity of 97.6% and a specificity of 96.0%
      of all lymph nodes analysed. For metastatic lymph nodes of solid neoplasmas
      (mainly bronchial carcinoma) sensitivity was even 98.7% (90.6% for malignant
      lymphomas). In conclusion, fine needle lymph node aspiration cytology is a quick,
      reliable, technically simple method for further assessment of enlarged lymph
      nodes in order to distinguish between benign and malignant causes. Further
      differentiation of the underlying type of malignant origin can be achieved with
      high efficacy. Thus, in the hands of a qualified investigator, fine needle lymph
      node aspiration cytology is a suitable method for use on a bed-side basis.

PMID- 12813668
TI  - [The anorexia-cachexia syndrome in bronchial carcinoma--pathophysiology
      therapeutic approaches].

PMID- 12813669
TI  - [Asthma due to grain dust].
AB  - The actual literature as well as two case reports described in detail show that
      grain dust induces asthmatic reactions and ODTS which are obviously not of
      allergic origin. For diagnosis occupational-type exposure tests are decisive
      whereas allergological testing usually is not. Endotoxins which are present in
      the grain dust samples in high concentrations have to be regarded as the major
      causative components. To avoid irreversible lung function impairment a
      comprehensive early diagnosis is necessary. Generally, a remarkable reduction of
      exposure to dust with high levels of airborne endotoxin in agriculture has to be
      achieved since in many workplaces corresponding exposures are still rather high.

PMID- 12813670
TI  - [Why history of pneumology?].

PMID- 12813671
TI  - [Tobacco- or alcohol-attributable inpatient treatments].
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to determine how many
      inpatient treatments are attributable to tobacco smoking or alcohol risk-drinking
      in a high tobacco smoking and alcohol per capital consumption country. PATIENTS
      AND METHODS: Relative mortality risks from international studies, inpatient
      diagnoses in the year 1997 (n = 12,803,729), rates of tobacco smokers and alcohol
      risk drinkers from Germany (microcensus 1995, n = 169,403; German National Health
      Survey 1990/1991, n = 7450) were the data base. RESULTS: Of all inpatient
      treatment cases in the year 1997, 9.9 % (n = 1,273,651) were tobacco- or alcohol
      attributable. The inpatient stays took 1.5 days more than those who were not
      tobacco- or alcohol-attributable. CONCLUSION: It is concluded that early
      detection and early intervention are needed for the decrease of the number of
      inpatient treatments.

PMID- 12813672
TI  - [Pylephlebitis with air in the portal vein system. An unusual focus in a patient
      with sepsis].
AB  - HISTORY AND CLINICAL FINDINGS: A 30-year-old male was transferred to the
      intensive care unit with worsening sepsis of unknown origin and a known history
      of Crohn's disease. The patient presented with a five-day history of nausea,
      fever, and serous diarrhea. Clinical examination of the abdomen was unremarkable
      except for mild epigastric pain on palpation. INVESTIGATIONS: Computed tomography
      (CT) of the abdomen revealed gas within the intrahepatic branches of the portal
      venous system, thickening of the wall of the neoterminal ileum, and mild ascites.
      In addition, ultrasonography showed acute thrombosis of the portal vein and the
      superior mesenteric vein. No wall perfusion was seen in either the neoterminal
      ileum or the ascending colon on color Doppler sonography. DIAGNOSIS, TREATMENT
      AND COURSE: Based on the combination of portal vein thrombosis along with venous
      gas in the portal venous system and absence of intestinal perfusion, the
      diagnosis of pylephlebitis with septic shock was suspected and a laparotomy was
      performed. Intraoperative exploration revealed phlegmonous terminal ileitis, a
      significant amount of cloudy fluid, and thrombosis of the mesenteric vein. A
      right-sided hemicolectomy with ileotransversostomy was performed. Histologic
      examination confirmed Crohn's disease that was associated with vasculitis and, in
      particular, with thrombophlebitis and subsequent transmural bowel necrosis.
      Antibiotic and anticoagulation therapy was resumed without further complications.
      CONCLUSION: In the differential diagnosis of sepsis, especially in combination
      with abdominal pain or gas in the portal venous system, pylephlebitis should be
      taken into account. Because of the high mortality, immediate further diagnostic
      testing and appropriate therapy of this rare diagnosis are necessary.

PMID- 12813673
TI  - [Rare cause of chronic abdominal pain: retractile mesenteritis].
AB  - HISTORY AND ADMISSION FINDINGS: A 69-year-old man had a history of chronic
      abdominal pain and intermittent fever for more than 10 years. Due to acute
      epigastric pain and intermittent fever with night sweat for one week he was
      admitted for further investigation. On physical examination there was tenderness
      in the right upper and lower epigastrium without a palpable mass. INVESTIGATIONS:
      Laboratory figures showed signs of inflammation with a CRP of 103 mg/l. Leucocyte
      counts were normal without left shift. CT and MRI scans showed a sharp-edged mass
      of 10 x 8 cm in diameter in the retroperitoneal area with big vessels running
      through it. Laparoscopic biopsy confirmed the suspected diagnosis of retractile
      mesenteritis. TREATMENT AND COURSE: Under therapy with oral progesterone
      (Utrogestan 1 x 100 mg/d) and prednisone (Prednison 1 x 50 mg/d) there was fast
      symptomatic relief. A CT scan 2 months after initial diagnosis showed clear
      regression of the tumor. CONCLUSION: Retractile mesenteritis is a rare cause of
      chronic abdominal pain with variable symptoms. Its aetiology is unknown. In case
      of bowel ischemia a surgical approach is preferred, milder forms may be treated
      with immunosuppressive agents as well as oral progesterone. Progesterone has
      exhibited positive effects on fatty tissue with successful treatment in desmoid
      tumors and retroperitoneal fibrosis. Here in we could demonstrate its safe and
      efficient use in a patient with retractile mesenteritis.

PMID- 12813674
TI  - [Mitomycin-induced hemolytic-uremic syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 58-year-old patient suffered from rapidly
      progressing renal insufficiency and 11 kg weight-loss three months after adjuvant
      treatment of a carcinoma of the lower bowel (G 2 T 3 N 1 M 0 ) with mitomycine C.
      At the point of hospitalisation the patient was anuric while suffering from
      pulmonary oedema, hemolytic anemia and thrombocytopenia. INVESTIGATIONS: Computed
      tomography and bronchial endoscopy showed pulmonary haemorrhage. Recurrence of
      carcinoma or metastases were excluded. Renal biopsy revealed mesangiolysis and
      concentric intimaproliferation (onion skinning). Beside haemolytic anaemia and
      fragmentocytes toxic damage of the bone marrow was found. TREATMENT AND COURSE:
      After one week treatment in the intensive care unit because of respiratory
      insufficiency recovery was observed under plasma separation and high dose
      corticosteroid therapy. Disease activity involved renal failure, bone marrow
      insufficiency, microangiopathic anaemia thrombopenia and pulmonary haemorrhage.
      CONCLUSION: Lung involvement in the course of haemolytic uremic syndrome is rare
      and carries a high lethality. The case illustrates the need of detailed
      diagnostic for correct treatment of haemolytic uremic syndrome. If chemotherapy
      is required in patients with pre-existing or intercurrent renal failure dose
      adaptation is necessary to avoid dose-dependent toxicity of mitomycine C.

PMID- 12813675
TI  - [Acute and chronic inflammatory neuropathies--therapy].

PMID- 12813677
TI  - [The legal situation concerning the sterilization of mentally handicapped
      persons].

PMID- 12813676
TI  - [Gestational diabetes mellitus: screening, oral glucose tolerance test and blood
      sugar daily profile].

PMID- 12813678
TI  - [Severe heart failure: when are the therapeutic possibilities of cardiology not
      very promising?].

PMID- 12813679
TI  - [Adverse drug reactions].

PMID- 12813683
TI  - Benign esophageal tumors: introduction, incidence, classification, and clinical
      features.
AB  - Benign esophageal tumors comprise a diverse group of disorders that are rare in
      relation to malignant tumors or other benign conditions. The current article
      summarizes the literature with regard to the incidence and prevalence of benign
      tumors of the esophagus and discusses the various methods used to categorize
      these conditions. Summaries of important clinical features are provided for
      leiomyomas, esophageal cysts, fibrovascular polyps, papillomas, granular cell
      tumors and others.

PMID- 12813684
TI  - Benign tumors of the esophagus: radiologic evaluation.
AB  - Benign tumors of the esophagus can be classified as mucosal or submucosal in
      origin. The most common mucosal lesions include squamous papillomas, adenomas
      arising in Barrett's mucosa, inflammatory esophagogastric polyps, and glycogenic
      acanthosis. These benign mucosal lesions can often be diagnosed on double
      contrast esophagrams based on their characteristic radiographic findings. Major
      submucosal or intramural lesions include leiomyomas, leiomyomatosis,
      fibrovascular polyps, granular cell tumors, and duplication cysts. Despite their
      infrequency, these lesions also can often be diagnosed on esophagography and/or
      CT based on their characteristic radiographic findings. The purpose of this
      article is to review in some detail the radiographic features of these various
      benign tumors of the esophagus.

PMID- 12813685
TI  - Benign esophageal tumors: esophagoscopy and endoscopic esophageal ultrasound.
AB  - Benign esophageal tumors are uncommon. Flexible fiberoptic esophagoscopy
      (esophagoscopy) has improved detection but is ineffective in classification of
      extramucosal tumors. Endoscopic esophageal ultrasound (EUS) is vital in
      diagnosis. Small lesions that have either a homogeneous anechoic, intermediate,
      or hyperechoic pattern are almost exclusively benign. These findings, plus the
      determination of the layer of origin within the esophageal wall, permit precise
      and accurate noninvasive diagnosis. The diagnosis of a benign esophageal tumor by
      esophagoscopy and EUS in an asymptomatic patient requires, at most, surveillance
      but no therapy.

PMID- 12813686
TI  - Treatment of benign esophageal tumors by endoscopic techniques.
AB  - Gastrointestinal endoscopy has changed in recent years from a largely diagnostic
      to a highly therapeutic procedure. Technical advances in endoscopic ultrasound as
      well as new devices designed for endoscopic mucosal resection (EMR) have opened
      the field to many therapeutic possibilities. Endoscopic resection is technically
      challenging, and while our colleagues in the Far East have been using such
      techniques for over a decade, EMR in the West is still in its infancy. The
      decision to resect a benign esophageal tumor must take several factors into
      account including whether the patient is symptomatic; characteristics of the
      particular tumor (including the potential for malignant transformation, risk of
      bleeding, and obstruction); and the available therapeutic options. Endoscopic
      resection of benign esophageal tumors is an attractive option as it is a safe and
      minimally invasive procedure. Its use is limited, however, to smaller tumors
      arising from the mucosal or submucosal layers. In this article we examine the
      techniques used in endoscopic mucosal resection and review the literature on this
      subject.

PMID- 12813687
TI  - Minimally invasive techniques for resection of benign esophageal tumors.
AB  - With the emergence of minimally invasive surgery (MIS), laparoscopy and
      thoracoscopy have become feasible and safe alternatives to open surgical
      procedures in the management of esophageal leiomyomas. The indications for MIS
      resection of leiomyomas at our institution include the presence of symptoms,
      confirmation of pathology to exclude malignancy, tumors greater than 2 cm in size
      or tumors that show evidence of growth. Our approach of choice is right video
      assisted thoracoscopic surgery (VATS) for tumors of the thoracic esophagus and
      laparoscopy for tumors of the intra-abdominal esophagus or gastroesophageal
      junction. A detailed description of these surgical approaches is outlined in the
      following chapter. At our institution, nine patients, 8 males and 2 females with
      a mean age of 54 years (range 42-67 years) had a minimally invasive surgical
      resection of an esophageal leiomyoma between 1995 and 2001. The surgical
      approaches included right VATS enucleation (6) and laparoscopic enucleation (3).
      There were no major morbidities, including postoperative leaks or mortalities.
      The mean hospital stay was 2.3 days. All tumors were benign leiomyomas with
      average size of 2.73 cm (range 0.9-8 cm) and there was no evidence of recurrence
      at a mean follow-up of 10 months. Video-assisted enucleation has shown in our
      institution, as well as in others, that the procedure can be performed safely
      with low mortality and morbidity. A VATS or laparoscopic approach to the removal
      of leiomyomas should be the treatment of choice in centers experienced in
      minimally invasive surgery.

PMID- 12813689
TI  - Current results of off-pump coronary artery bypass surgery.
AB  - Whether to use or not use cardiopulmonary bypass-cardioplegic arrest to perform
      coronary artery bypass surgery is the main controversy presently facing our
      surgical specialty. The reported clinical outcomes are mainly retrospective and
      highly debatable for conclusiveness regarding the benefits of off-pump surgery.
      As more centers and larger patient cohorts are analyzed and reported,
      particularly over the last 2 years, off-pump surgery appears to provide
      significantly improved outcomes with decreased bleeding and transfusion
      requirements, less myocardial enzyme release, less ventilatory time, and
      decreased hospital stay and costs. Reported off-pump benefits for the major
      outcomes of operative mortality and stroke are encouraging, but less conclusive.
      From experienced centers, early off-pump angiographic graft patency has been
      comparable to previously published conventional results. High-risk, elderly
      patients may benefit the greatest from off-pump surgery. Although in relative
      technical infancy, off-pump coronary artery bypass grafting has demonstrated
      enough benefit outcomes that it is no longer an experimental procedure, but a
      valid surgical revascularization method requiring further investigation and
      continued usage.

PMID- 12813690
TI  - Neurologic outcomes after coronary artery bypass grafting with and without
      cardiopulmonary bypass.
AB  - Neurologic injury, in the form of either stroke or more subtle neurocognitive
      impairment, is a frequent and potentially devastating complication of coronary
      artery bypass grafting (CABG). The etiology of CABG-associated neurologic injury
      is likely multifactorial, with the phenomena of cerebral hypoperfusion and
      embolism being the major contributors. Several perioperative strategies have been
      developed in an effort to reduce the incidence of CABG-associated neurologic
      complications. Hypothermic cerebral perfusion, alpha stat acid-base management,
      and slow patient rewarming have been shown by several investigators to minimize
      adverse neurologic sequelae associated with the use of cardiopulmonary bypass.
      Performing CABG without cardiopulmonary bypass (off-pump CABG), meanwhile, has
      been shown to reduce the risk of perioperative stroke, especially in high-risk
      patients such as the elderly. Whether off-pump CABG reduces the incidence of less
      severe neurocognitive impairment has not yet been clearly established and merits
      further investigation in the form of large, multicenter, randomized trials. Other
      technical innovations, such as the use of sutureless and clampless aortic
      anastomotic devices, also may be able to further minimize the neurologic
      complications associated with CABG.

PMID- 12813691
TI  - Complications related to off-pump bypass grafting.
AB  - Surgical myocardial revascularization is a technique undergoing critical
      reevaluation in an attempt to reduce operative morbidity and mortality. As the
      age and number of comorbidities in the surgical population presenting for bypass
      increases, improved strategies to lessen operative risk have evolved. The use of
      off-pump bypass grafting to avoid the detrimental effects of extracorporeal
      circulation demonstrates great promise in reducing operative complications.
      However, with new techniques come new challenges. Avoidance of the
      cardiopulmonary bypass circuit has been linked to the development of a
      hypercoagulable state postoperatively. Complications related to the unique
      management of the ascending aorta and target vessels during the performance of
      beating heart surgery are also being reported. Moreover, despite increasing
      experience in a number of centers, hemodynamic collapse does occur during off
      pump bypass, thereby requiring rapid institution of cardiopulmonary bypass.
      Continued scientific investigation and research should provide the tools to
      manage the unique obstacles encountered with off-pump coronary artery bypass.

PMID- 12813692
TI  - Anesthesia for off-pump coronary artery bypass grafting.
AB  - Off-pump coronary artery bypass presents special challenges for the
      anesthesiologist and surgeon, who must work closely together to provide optimal
      care. Displacement and immobilization of the heart for exposure of the coronary
      arteries, as well as occlusion of these vessels, can result in periods of
      significant hemodynamic instability. Appropriate preparation, guided therapy, and
      technical maneuvers can lessen such adverse hemodynamic impact. It is important
      for anesthesiologists to be aware of the special problems associated with this
      surgery, as well as the different therapies and maneuvers that can be useful in
      providing the best possible care. As surgeons develop greater expertise and
      better devices for the management of these patients, the number of coronary
      revascularizations without CPB is likely to increase.

PMID- 12813693
TI  - Beating heart coronary artery bypass: operative strategy and technique.
AB  - With beating heart techniques firmly established, coronary surgeons now have a
      variety of approaches from which to choose the best operation for each individual
      patient based upon their own personal and institutional experience. Selection of
      the best operative approach and combination of available techniques for each
      patient is a dynamic process and forms the basis of our operative strategy. We
      consider four basic alternative operative approaches in each patient based on
      specific physiologic and anatomic criteria. Success begins with a committed team
      and close collaboration between surgeon and anesthesiologist. Effective
      communication is essential to maintaining clinical stability and avoiding
      disaster. During beating heart surgery, global ischemia is eliminated and
      regional ischemia is managed by an individualized grafting strategy designed to
      minimize the area of regional myocardium that is ischemic during each
      anastomosis. Maneuvers are described that are designed to minimize compression,
      ischemia, and length of time that the heart is displaced and usually result in
      satisfactory exposure and hemodynamics. A proven successful operative strategy is
      outlined including 1) initial patient evaluation and preoperative procedure
      selection; 2) operative choreography; 3) incision and initial exposure; 4) an
      individualized revascularization strategy; and 5) target vessel exposure,
      stabilization, vascular control, and visualization. Most cardiac surgeons already
      possess the skills required to successfully adopt beating heart surgery. Knowing
      when to patiently wait, when to persist, and when to intervene is more important
      to the successful application of these techniques than any skill.

PMID- 12813694
TI  - Future technology for off-pump coronary artery bypass (OPCAB).
AB  - Over the past 5 years, many coronary artery surgeons have embraced technology and
      advanced the field of beating heart surgery to the point where off-pump coronary
      artery bypass (OPCAB) is becoming a mature procedure. Enabling technologies are
      now available for all stages of the procedure, including cardiac positioning,
      coronary artery stabilization, coronary artery visualization, and performance of
      the proximal and distal anastomoses. Despite these successes, only a minority of
      cardiac surgeons performs this procedure routinely. Proponents of OPCAB and the
      medical device industry will need to continue to develop new technologies to make
      OPCAB less technically challenging and more widely accepted. Progress towards
      routine single-vessel off-pump totally endoscopic coronary artery bypass has been
      slow. Translating the benefits of multivessel OPCAB to an endoscopic setting
      remains a formidable challenge that will require further technologic
      breakthroughs.

PMID- 12813722
TI  - Multipoint linkage disequilibrium mapping approach: incorporating evidence of
      linkage and linkage disequilibrium from unlinked region.
AB  - Gene mapping for complex diseases is still a challenge in genetic studies. For
      family-based studies, the single-locus methods for detecting linkage and linkage
      disequilibrium (LD) one at a time may not capture the assumed interaction between
      multiple causal genes efficiently. We propose a multipoint LD approach for
      assessing the evidence of linkage and LD in a targeted chromosomal region by
      incorporating evidence from an unlinked region using the case-parent trio design.
      The paternal and maternal preferential transmission statistics defined in Liang
      et al. ([2001] Am. J. Hum. Genet. 68:937-950) are the primary statistics for this
      approach. Our generalized estimating equation (GEE) method builds on a model
      using the expected preferential transmission statistic from the targeted region
      conditional on this same statistic from the unlinked region. The major assumption
      is that there is no more than one trait locus in both the targeted region and
      unlinked region. The map position of an unobserved trait locus and its confidence
      interval can be calculated. Finally, we apply this approach to the African
      American families drawn from the Collaborative Study on the Genetics of Asthma
      (CSGA). Previous analysis using this GEE approach developed by Liang et al.
      ([2001] Am. J. Hum. Genet. 68:937-950) suggested strong evidence of linkage and
      LD on chromosome 11, but only marginal evidence on chromosome 8. While
      conditioning on marker D11S937 on chromosome 11, a separate trait locus on
      chromosome 8 was estimated at tau(2) empty set = 11.67 cM, with a 95% confidence
      interval of (8.75, 14.59), and the test statistic shows significant evidence of
      linkage and LD (P-value=0.0198) in this region of chromosome 8.

PMID- 12813723
TI  - Finding starting points for Markov chain Monte Carlo analysis of genetic data
      from large and complex pedigrees.
AB  - Genetic data from founder populations are advantageous for studies of complex
      traits that are often plagued by the problem of genetic heterogeneity. However,
      the desire to analyze large and complex pedigrees that often arise from such
      populations, coupled with the need to handle many linked and highly polymorphic
      loci simultaneously, poses challenges to current standard approaches. A viable
      alternative to solving such problems is via Markov chain Monte Carlo (MCMC)
      procedures, where a Markov chain, defined on the state space of a latent variable
      (e.g., genotypic configuration or inheritance vector), is constructed. However,
      finding starting points for the Markov chains is a difficult problem when the
      pedigree is not single-locus peelable; methods proposed in the literature have
      not yielded completely satisfactory solutions. We propose a generalization of the
      heated Gibbs sampler with relaxed penetrances (HGRP) of Lin et al., ([1993] IMA
      J. Math. Appl. Med. Biol. 10:1-17) to search for starting points. HGRP guarantees
      that a starting point will be found if there is no error in the data, but the
      chain usually needs to be run for a long time if the pedigree is extremely large
      and complex. By introducing a forcing step, the current algorithm substantially
      reduces the state space, and hence effectively speeds up the process of finding a
      starting point. Our algorithm also has a built-in preprocessing procedure for
      Mendelian error detection. The algorithm has been applied to both simulated and
      real data on two large and complex Hutterite pedigrees under many settings, and
      good results are obtained. The algorithm has been implemented in a user-friendly
      package called START.

PMID- 12813724
TI  - Linkage analysis with sequential imputation.
AB  - Multilocus calculations, using all available information on all pedigree members,
      are important for linkage analysis. Exact calculation methods in linkage analysis
      are limited in either the number of loci or the number of pedigree members they
      can handle. In this article, we propose a Monte Carlo method for linkage analysis
      based on sequential imputation. Unlike exact methods, sequential imputation can
      handle large pedigrees with a moderate number of loci in its current
      implementation. This Monte Carlo method is an application of importance sampling,
      in which we sequentially impute ordered genotypes locus by locus, and then impute
      inheritance vectors conditioned on these genotypes. The resulting inheritance
      vectors, together with the importance sampling weights, are used to derive a
      consistent estimator of any linkage statistic of interest. The linkage statistic
      can be parametric or nonparametric; we focus on nonparametric linkage statistics.
      We demonstrate that accurate estimates can be achieved within a reasonable
      computing time. A simulation study illustrates the potential gain in power using
      our method for multilocus linkage analysis with large pedigrees. We simulated
      data at six markers under three models. We analyzed them using both sequential
      imputation and GENEHUNTER. GENEHUNTER had to drop between 38-54% of pedigree
      members, whereas our method was able to use all pedigree members. The power gains
      of using all pedigree members were substantial under 2 of the 3 models. We
      implemented sequential imputation for multilocus linkage analysis in a user
      friendly software package called SIMPLE.

PMID- 12813725
TI  - Analysis of multilocus models of association.
AB  - It is increasingly recognized that multiple genetic variants, within the same or
      different genes, combine to affect liability for many common diseases. Indeed,
      the variants may interact among themselves and with environmental factors. Thus
      realistic genetic/statistical models can include an extremely large number of
      parameters, and it is by no means obvious how to find the variants contributing
      to liability. For models of multiple candidate genes and their interactions, we
      prove that statistical inference can be based on controlling the false discovery
      rate (FDR), which is defined as the expected number of false rejections divided
      by the number of rejections. Controlling the FDR automatically controls the
      overall error rate in the special case that all the null hypotheses are true. So
      do more standard methods such as Bonferroni correction. However, when some null
      hypotheses are false, the goals of Bonferroni and FDR differ, and FDR will have
      better power. Model selection procedures, such as forward stepwise regression,
      are often used to choose important predictors for complex models. By analysis of
      simulations of such models, we compare a computationally efficient form of
      forward stepwise regression against the FDR methods. We show that model selection
      includes numerous genetic variants having no impact on the trait, whereas FDR
      maintains a false-positive rate very close to the nominal rate. With good control
      over false positives and better power than Bonferroni, the FDR-based methods we
      introduce present a viable means of evaluating complex, multivariate genetic
      models. Naturally, as for any method seeking to explore complex genetic models,
      the power of the methods is limited by sample size and model complexity.

PMID- 12813726
TI  - Evolutionary-based association analysis using haplotype data.
AB  - Association studies, both family-based and population-based, can be powerful
      means of detecting disease-liability alleles. To increase the information of the
      test, various researchers have proposed targeting haplotypes. The larger number
      of haplotypes, however, relative to alleles at individual loci, could decrease
      power because of the additional degrees of freedom required for the test. An
      optimal strategy would focus the test on particular haplotypes or groups of
      haplotypes, much as is done with cladistic-based association analysis. First
      suggested by Templeton et al. ([1987] Genetics 117:343-351), such analyses use
      the evolutionary relationships among haplotypes to produce a limited set of
      hypothesis tests and to increase the interpretability of these tests. To more
      fully utilize the information contained in the evolutionary relationships among
      haplotypes and in the sample, we propose generalized linear models (GLM) for the
      analysis of data from family-based and population-based studies. These models
      fully account for haplotype phase ambiguity and allow for covariates. The models
      are encoded into a software package (the Evolutionary-Based Haplotype Analysis
      Package, EHAP), which also provides for various kinds of exploratory data
      analysis. The exploratory analyses, such as error checking, estimation of
      haplotype frequencies, and tools for building cladograms, should facilitate the
      implementation of cladistic-based association analysis with haplotypes.

PMID- 12813727
TI  - Assessing accuracy in linkage analysis by means of confidence regions.
AB  - When statistical linkage to a certain chromosomal region has been found, it is of
      interest to develop methods quantifying the accuracy with which the disease locus
      can be mapped. In this paper, we investigate the performance of three different
      types of confidence regions, with asymptotically correct coverage probability as
      the number of pedigrees grows. Our setup is that of a saturated map of marker
      data. We allow for arbitrary combinations of pedigree structures, and treat
      various kinds of genetic models (e.g. binary and quantitative phenotypes) in a
      unified way. The linkage scores are weighted sums of the individual family
      scores, with NPL and lod scores as special cases. We show that the expected
      length of the confidence region is inversely proportional to the slope-to-noise
      ratio, or equivalently, inversely proportional to the product of the square of
      the noncentrality parameter and a certain normalized slope-to-noise ratio. Our
      investigations reveal that maximal expected linkage scores can be quite different
      from estimation-based performance criteria based on expected length of confidence
      regions. The main reason is that there is no simple relationship between peak
      height and peak slope of the mean linkage score. One application of our results
      is planning of linkage studies: given a certain genetic model, we can approximate
      the number of pedigrees needed to obtain a confidence region with given coverage
      probability and expected length.

PMID- 12813728
TI  - Testing linkage and gene x environment interaction: comparison of different
      affected sib-pair methods.
AB  - The aim of this study was to compare, under different models of gene-environment
      (G x E) interaction, the power to detect linkage and G x E interaction of
      different tests using affected sib-pairs. Methods considered were: 1) the maximum
      likelihood lod-score (MLS), based on the distribution of parental alleles
      identical by descent (IBD) in affected sibs; 2) the sum of the MLS (sMLS)
      calculated in affected sib-pairs with 2, 1, or 0 sibs exposed; 3) the predivided
      sample test (PST), which compares the IBD distribution between affected sib-pairs
      with 2, 1, or 0 sibs exposed; 4) the triangle test statistic (TTS), which uses
      the IBD distribution among discordant affected sib-pairs (one exposed, one
      unexposed); and 5) the mean interaction test (MIT), based on the regression of
      the proportion of alleles shared IBD among affected sib-pairs on the exposure
      among sib-pairs. The MLS, sMLS, and MIT allow detection of linkage. However, the
      sMLS and MIT account for a possible G x E interaction without testing it. In
      contrast, the PST and the TTS allow detection of both linkage and G x E
      interaction. Results showed that when exposure cancels the effect of the gene, or
      changes the direction of this effect (i.e., the protective allele becomes the
      risk allele), the PST, sMLS, and MIT may provide, under some models, greater
      power to detect linkage than the MLS. Under models where exposure changes the
      direction of the effect of the gene, the TTS test may also be more powerful than
      the other tests accounting for G x E interaction. Under the other models, the MLS
      remains the most powerful test to detect linkage. However, only the PST and TTS
      allow the detection of G x E interaction.

PMID- 12813729
TI  - Genetic association tests for family data with missing parental genotypes: a
      comparison.
AB  - We consider three tests for genetic association in data from nuclear families
      (the Family-Based Association Test (FBAT) test proposed by Rabinowitz and Laird
      ([2000] Hum. Hered. 50:211-223), a second test proposed by Rabinowitz ([2002] J.
      Am. Stat. Assoc. 97:742-758), and the Family Genotype Analysis Program (FGAP)
      nonfounder or partial score test proposed by Clayton ([1999] Am. J. Hum. Genet.
      65:1170-1177) and Whittemore and Tu ([2000] Am. J. Hum. Genet. 66:1329-1340)). We
      show that each test statistic arises from the efficient score of the family data
      as the solution to a set of constraints on its null expectation. Moreover, the
      FBAT and Rabinowitz tests (but not the FGAP test) are locally the most powerful
      among all tests satisfying their constraints. We used simulations to examine how
      the three tests perform in situations when their assumptions are violated and the
      number of families is not huge. We found that the FBAT test tended to have less
      power than the other two tests, particularly when applied to families in whom all
      offspring were affected. The Rabinowitz and FGAP tests performed similarly,
      although the latter tended to extract more information from families containing
      one typed parent. While none of the tests showed good power to detect rare,
      recessively acting genes, the Rabinowitz test with a sample variance estimate
      performed particularly poorly in this case. However, the Rabinowitz test with a
      model-based variance had power comparable to that of the FGAP test, and more
      accurate type I error rates. We conclude that for the situations we considered,
      the Rabinowitz test with model-based variance has good power without forfeiting
      robustness against misspecification of parental genotype probabilities. However,
      its utility is limited by the lack of a simple algorithm to apply it to families
      with varying structures and phenotypes.

PMID- 12813731
TI  - Molecule-based magnetic materials.

PMID- 12813732
TI  - Supertetrahedra in sulfides: matter against mathematical series?

PMID- 12813733
TI  - Pd-catalyzed enantioselective allylic substitution: new strategic options for the
      total synthesis of natural products.

PMID- 12813734
TI  - Metal alkynyl sigma complexes: synthesis and materials.
AB  - Metal alkynyl complexes hold a fascination for synthetic chemists, structural
      chemists, and materials scientists alike. Harnessing the unique overlap of metal
      and carbon orbitals is a challenge that can be overcome in many ways and hence,
      there are many synthetic routes toward M-C=C-bond-forming reactions that utilize
      a wide variety of transition-metal and alkynyl reagents. Some methods can be
      widely applied, while others are specific to a particular metal or compound. The
      linear geometry of the alkynyl unit and its pi-unsaturated character have led to
      metal alkynyls becoming attractive building blocks for molecular wires and
      polymeric organometallic materials, which can possess interesting properties,
      such as optical nonlinearity, luminescence, liquid crystallinity, and electrical
      conductivity. A unique, multifaceted approach, often combining talents from all
      three of the above chemical disciplines, has served as a driving force behind the
      intense research into the development of metal alkynyl sigma complexes, the
      progress of which, particularly in the last ten years, is summarized in this
      review.

PMID- 12813735
TI  - Reversible enantiofacial differentiation of a single heterocyclic substrate by
      supramolecular receptors.

PMID- 12813736
TI  - [Ge9[Si(SiMe3)3]3]-: a soluble polyhedral Ge9 cluster stabilized by only three
      silyl ligands.

PMID- 12813737
TI  - Coordination geometry of the discrete pentafluoroaluminate dianion [AlF5]2-.

PMID- 12813738
TI  - A pseudotetrahedral, high-oxidation-state organonickel compound: synthesis and
      structure of bromotris(1-norbornyl)nickel(IV).

PMID- 12813739
TI  - Biogenesis of 3-alkylpyridine alkaloids in the marine mollusc Haminoea
      orbignyana.

PMID- 12813740
TI  - Hydrogenation of arenes over catalysts that combine a metal phase and a grafted
      metal complex: role of the single-site catalyst.

PMID- 12813741
TI  - Highly ordered mesoporous silicon oxynitride materials as base catalysts.

PMID- 12813742
TI  - Self-healing systems having a design stimulated by the vertebrate spine.

PMID- 12813743
TI  - Palladium(0)-catalyzed tandem cyclization of allenenes.

PMID- 12813744
TI  - Phenyl[bis(triphenylphosphanemethylenido)]borane: a zwitterionic chelating ligand
      exhibiting allyl-type coordination.

PMID- 12813745
TI  - Total synthesis of TMC-95A.

PMID- 12813746
TI  - Tin-free radical allylation of B-alkylcatecholboranes.

PMID- 12813747
TI  - Synthesis and structural characterization of thermally stable group 13 hydride
      complexes derived from a gallium(I) carbene analogue.

PMID- 12813748
TI  - Membership rules for a molecular box: the admission process and protection
      provided to guest molecules.

PMID- 12813749
TI  - Targeted gene delivery to cancer cells: directed assembly of nanometric DNA
      particles coated with folic acid.

PMID- 12813750
TI  - Modular assembly of two-dimensional metal-organic coordination networks at a
      metal surface.

PMID- 12813751
TI  - X-ray structures of binary and ternary enzyme-product-inhibitor complexes of
      matrix metalloproteinases.

PMID- 12813752
TI  - Synthesis, photophysical properties, and nanocrystal formation of a new class of
      tetra-N-substituted perylenes.

PMID- 12813753
TI  - Novel ruthenium- and platinum-catalyzed sequential reactions: synthesis of tri-
      and tetrasubstituted furans and pyrroles from propargylic alcohols and ketones.

PMID- 12813754
TI  - Ferrous wheels, ellipse [(tBu3SiS)FeX]n, and cube [(tBu3SiS)Fe(CCSitBu3)]4.

PMID- 12813756
TI  - Accuracy of trisomy 18 screening using the second-trimester triple test.
AB  - OBJECTIVE: To assess the accuracy of the calculated risk for trisomy 18 assigned
      to individual women screened with the second-trimester triple test. METHODS: The
      study was based on 382598 women screened in the Ontario Maternal Serum Screening
      Programme between October 1993 and September 2000. Of the women screened, 111
      cases of trisomy 18 were identified. Originally, 92874 women were screened using
      a risk cut-off level method. Estimated risks of trisomy 18 were calculated by
      applying published population parameters for the remaining women screened using a
      fixed analyte cut-off method. Women were ranked according to their individual
      risk for trisomy 18 syndrome in decreasing order and divided into 12 groups. The
      mean calculated risks of having an affected pregnancy at term for each group were
      compared with the birth prevalence of the corresponding group after allowing for
      spontaneous fetal losses. RESULTS: Agreement between the mean calculated risks
      and the observed prevalence was seen across the entire risk range, although women
      identified as having high-risk pregnancies had an actual prevalence that was
      somewhat lower than that estimated by the screen. CONCLUSION: The calculated risk
      for trisomy 18 syndrome assigned to the individual woman on the basis of the risk
      cut-off method accurately reflects their risk of having a term trisomy 18
      syndrome pregnancy.

PMID- 12813757
TI  - Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive
      pregnancies at risk.
AB  - Epidermolysis bullosa (EB) is a group of inherited disorders characterized by
      increased skin fragility, resulting in blisters and erosions after minor trauma.
      Mutations in 10 structural genes expressed in the cutaneous basement membrane
      zone have been reported. The DebRA Molecular Diagnostics Laboratory at Jefferson
      Medical College has performed 144 DNA-based prenatal diagnoses since 1993 in
      families at risk for recurrence of the most severe forms of EB, including the
      recessive dystrophic EB (RDEB), junctional EB (JEB), EB with pyloric atresia (EB
      PA), and EB simplex (EBS). A mutation-detection strategy using either
      conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance
      liquid chromatography (dHPLC) scanning analysis, followed by nucleotide
      sequencing, was applied to most cases with DEB and to all JEB, EB-PA, and EBS
      families. For some RDEB families, linkage analysis was performed, either alone
      when the inheritance pattern was clear or in combination with one mutation. Among
      the 144 prenatal diagnoses, 63 were for RDEB, 69 for JEB, 6 for EB-PA, and 6 for
      EBS. Twenty-eight normal, 73 heterozygous carrier, and 28 affected RDEB, JEB, and
      EB-PA pregnancies were reported in these recessively inherited diseases. Two
      affected and four normal pregnancies were predicted in dominantly inherited EBS.
      Among the 144 pregnancies, 9 were terminated without confirmation, 13 cases were
      lost to follow-up, and 6 pregnancies are ongoing. There were 6 families with
      inconclusive results due either to recombination events between flanking markers,
      absence of informative markers for one allele, or lack of sample from the
      previously affected child. There were three discordant results, one that was
      explained by maternal contamination of the chorionic villus sample and two that
      were unresolved. Overall, the availability, relative ease, and over 98% success
      rate make molecular DNA-based prenatal diagnosis a viable option for EB families
      at risk.

PMID- 12813758
TI  - Prenatal diagnosis of factor X deficiency using a combination of direct mutation
      detection and linkage analysis with an intragenic single nucleotide polymorphism.
AB  - OBJECTIVE: To present a family in which it was possible to perform prenatal
      diagnosis for recessively inherited factor X deficiency using both direct
      mutation detection as well as linkage analysis. METHODS: In a family where both
      parents were known to be carriers of factor X deficiency, fetal DNA was obtained
      from an ongoing pregnancy by CVS in the first trimester. Direct DNA sequencing
      was used to detect a previously identified factor X mutation, and linkage
      analysis using a single nucleotide polymorphism (SNP) was used to follow the
      segregation of the other parent's factor X alleles. RESULTS: Our studies
      predicted the fetus in question to be a heterozygote carrier of factor X
      deficiency, and this was demonstrated to be correct at birth. CONCLUSIONS: This
      is the first reported case of prenatal diagnosis of factor X deficiency. In
      addition, this case demonstrates the remarkable utility of SNPs in linkage
      analysis of rare genetic disorders.

PMID- 12813759
TI  - Discordant prenatal diagnosis of trisomy 21 due to mosaic structural
      rearrangements of chromosome 21.
AB  - OBJECTIVES: Trisomy 21 mosaicism associated with a structural rearrangement of
      chromosome 21 is uncommon. We report on two prenatal diagnoses in which
      karyotypes showed mosaicism with an aberrant cell line, including a structural
      rearrangement of chromosome 21. METHODS: Both these cases were associated with
      increased nuchal translucency. Conventional and molecular cytogenetic analyses
      were performed on uncultured and cultured trophoblast and amniotic fluid cells.
      RESULTS: In Case 1, analysis of trophoblast cells revealed an abnormal karyotype
      of 47,XX,+mar.ish der(13/21)(D13Z1/D21Z1+)/46,XX. The amniocentesis showed a free
      non-mosaic trisomy 21. In Case 2, the trophoblast direct analysis showed a normal
      male karyotype whereas the long-term culture revealed a mosaicism for a dicentric
      long-arm isochromosome 21: 46,XY,idic(21)(p11)/45,XY,-21/46,XY. Amniocentesis
      showed an unbalanced non-mosaic karyotype 46,XY,idic(21)(p11) resulting therefore
      in trisomy for the long arm of chromosome 21. CONCLUSION: Our cases underline the
      importance of combining the direct analysis and long-term culture of trophoblast
      and emphasise the need for confirmatory studies in other tissues when mosaicism
      of structural rearrangement is encountered in chorionic villi. The meiotic and
      mitotic mechanisms of formation of these structural rearrangements of chromosome
      21 are discussed.

PMID- 12813760
TI  - Early vaginal bleeding and first-trimester markers for Down syndrome.
AB  - OBJECTIVES: To assess the effect of early vaginal bleeding on first-trimester
      markers for Down syndrome. METHODS: A retrospective study was conducted on 2330
      normal singleton fetuses who underwent first-trimester combined screening for
      Down syndrome based on ultrasound and maternal serum markers. Fetal nuchal
      translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A),
      free beta-hCG and the false-positive rate of the test were compared between
      pregnancies with (n = 253) and without (n = 2077) a history of early vaginal
      bleeding. RESULTS: The mean +/- SD log(10) MoM for NT, PAPP-A and free beta-hCG
      was -0.024 +/- 0.101, 0.007 +/- 0.244, 0.047 +/- 0.273 and -0.011 +/- 0.108, 
      0.006 +/- 0.223, 0.008 +/- 0.264 in pregnancies with and without a history of
      early vaginal bleeding, with a p value of 0.07, 0.40 and 0.03 respectively. The
      false-positive rate was 2.4% and 3.6% (p = 0.33). CONCLUSIONS: An earlier episode
      of vaginal bleeding is associated with an increase in maternal serum free beta
      hCG levels at first-trimester combined screening for Down syndrome. However, this
      phenomenon is unlikely to significantly affect the false-positive rate of the
      test.

PMID- 12813761
TI  - Cystic fibrosis: selecting the prenatal screening strategy of choice.
AB  - Cystic fibrosis is a serious disorder. Research into the treatment of affected
      individuals is in progress, but a cure is not expected in the near future. In
      this review, we demonstrate that prenatal screening for cystic fibrosis meets the
      requirements for a worthwhile screening programme. We explain the reasons that
      have led us to conclude that one approach ('couple screening') is the method of
      choice. The couple-based approach calls for reporting results to the couple as a
      unit. Only if both parents are found to be carriers is the result designated
      screen-positive and an amniocentesis or chorionic villus sampling offered. This
      offers a substantial reduction in the proportion of women with unaffected
      pregnancies with positive results (the false-positive rate) compared with other
      methods without reducing the detection of affected pregnancies. It also avoids
      creating a screen-positive group for which no definitive diagnosis is available.
      This is a problem with other screening methods. The couple method can achieve a
      72% detection rate for a 0.1% false-positive rate. The screening method is
      simple, non-invasive, reliable, safe and reasonably cost effective. Existing
      programmes have shown that screening using this method is acceptable to health
      care professionals and patients. Setting up a national prenatal screening
      programme for cystic fibrosis is timely and should be implemented using the
      couple screening method.

PMID- 12813762
TI  - Amniotic fluid human chorionic gonadotrophin and alpha-fetoprotein levels in
      pregnancies conceived after assisted reproduction.
AB  - OBJECTIVES: To study the alteration in the second-trimester maternal serum levels
      of human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) in pregnancies
      conceived after assisted reproduction. METHODS: We compared the amniotic fluid
      hCG and AFP concentrations of 45 pregnancies with fresh embryo transfer and 25
      pregnancies with frozen-thawed embryo transfer with 269 spontaneous pregnancies.
      Wilcoxon rank-sum test was used for analysis. RESULTS: The median amniotic fluid
      hCG MoM in pregnancies conceived after frozen-thawed embryo transfer was
      significantly increased to 1.41 compared to 1.00 (p = 0.01) in naturally
      occurring pregnancies and 0.96 (p = 0.049) in pregnancies after fresh embryo
      transfer. Further analysis showed that this was only observed in frozen embryos
      fertilized by conventional insemination with MoM of 1.59. The AFP MoMs were
      similar among the groups. CONCLUSIONS: The observed raised amniotic fluid hCG
      level in IVF-FET pregnancies may reflect the elevated maternal serum level in
      these pregnancies. Further studies should be directed towards exploring the
      underlying pathophysiology.

PMID- 12813763
TI  - A classification of pregnancy losses after invasive prenatal diagnostic
      procedures: an approach to allow comparison of units with a different case mix.
AB  - OBJECTIVE: Pregnancy loss rates after prenatal invasive procedures such as
      amniocentesis (Amnio), chorionic villous sampling (CVS) and fetal blood sampling
      (FBS) vary with an underlying indication for the procedure and due to different
      background risk of miscarriage. Loss rates need to be quantified and available
      for counselling. We developed a classification of pregnancy losses that will help
      in calculating procedure-related pregnancy loss rates and allow comparison
      between units with a different case mix. METHODS: The procedure-related pregnancy
      loss rate was obtained by subtracting the losses in pregnancies with known lethal
      conditions and those occurring more than two weeks after the procedure from total
      pregnancy losses. RESULTS: Out of 436 CVSs, there were 18 losses. Of these, 14
      had a known lethal condition and 3 occurred after 2 weeks of CVS. In only one
      case, there was no known lethal abnormality and the loss occurred within 2 weeks.
      Thus, the total pregnancy loss rate was 4.1% and the procedure-related loss rate
      was 0.23% (95% CI; 0.0061-1.28). The procedure-related loss rates for Amnio 0.7%
      (95% CI; 0.2-1.8) and FBS 1.19 (95% CI; 0.14-4.23) were calculated in a similar
      way. CONCLUSIONS: We present a method of recording pregnancy loss after prenatal
      invasive procedures, which would be useful for benchmarking comparison between
      units and pre-procedural counselling.

PMID- 12813764
TI  - Sirenomelia, the mermaid syndrome--detection in the first trimester.
AB  - The sirenomelia sequence with fusion, rotation, hypotrophy or atrophy of the
      lower limbs in combination with severe urogenital and gastrointestinal
      malformations is a rare and usually lethal disorder. We present the case of a 28
      year-old woman, who was referred to our department because of an intraabdominal
      cystic structure in the 9th week of gestation. Subsequent scans confirmed the
      diagnosis of a sirenomelia sequence with the fusion of the lower extremities
      without fusion of the bones according to Stocker I classification. The size of
      the intraabdominal cyst decreased during follow-up. After counseling, termination
      of pregnancy was induced. The postmortem X-ray confirmed the ultrasound
      diagnosis. The exact etiological mechanism of this malformation is still unknown.
      An early alteration of the embryological vascular network damaging the caudal
      mesoderm is thought to lead to arrested development of the lower limbs and other
      affected organs. The cyst we saw in the 9th week might fit with this theory,
      either as an expression of the complex malformation of the lower abdomen or as
      the sonographic appearance of necrosis.

PMID- 12813765
TI  - Absence of fetal nasal bone and aneuploidies at first-trimester nuchal
      translucency screening in unselected pregnancies.
AB  - OBJECTIVES: The absence of nasal bone (NB) has been noted in trisomy 21 fetuses
      at first-trimester ultrasound, in high-risk pregnancies. In this study, the nasal
      bone was evaluated in relation to fetal karyotype, in unselected pregnancies.
      METHODS: From September 2001 to September 2002, the fetal facial profile was
      examined at the 11 to 14 weeks' scan for screening by nuchal translucency (NT).
      Risks for trisomy 21 were calculated using the Fetal Medicine Foundation's
      software, and the presence or absence of NB was noted. Prenatal karyotype and
      pregnancy outcomes were recorded. RESULTS: NT screening was performed in 5532
      fetuses from 5425 pregnancies (85 twins, 8 triplets, 2 quadruplets). The
      visualization of fetal profile was obtained in 5525 fetuses (99.8%), and in 5491
      fetuses (99.4%) the NB was present and in 34 cases (0.6%) it was absent. Fetal
      karyotype and pregnancy outcome were available in 3503 pregnancies, and 40
      chromosomal abnormalities were diagnosed (27 trisomies 21, 5 trisomies 18, 2
      trisomies 13, 3 Turner syndromes, 1 partial trisomy 9 and 2 others). The NB was
      absent in 19 (70%) trisomies 21, 4 trisomies 18 (80%), 2 Turner syndromes (66%),
      in the partial trisomy 9, in 7 normal karyotype fetuses (0.2%), and in a case
      with spontaneous first-trimester abortion before prenatal diagnosis. A
      significant difference was found between NT thickness, expressed as a multiple of
      the median, in trisomy 21 fetuses with present and absent nasal bone.
      CONCLUSIONS: The absence of NB at 11 to 14 weeks is more frequent in fetuses with
      trisomy 21 and other aneuploidies than in normal karyotype fetuses.

PMID- 12813766
TI  - The influence of IVF, multiple gestation and miscarriage on the acceptance of
      genetic amniocentesis.
AB  - OBJECTIVES: To determine the effect of in vitro fertilization (IVF), multiple
      gestation, and history of unkaryotyped miscarriage on the acceptance of genetic
      amniocentesis. METHODS: We studied women expected to be at least 35 years of age
      at the estimated date of delivery without family history of chromosomal
      abnormalities or fetal structural anomalies. The influence of IVF, multiple
      gestation, and history of miscarriage on the acceptance rate of genetic
      amniocentesis was evaluated. Chi-square test and logistic regression were used
      for analysis. RESULTS: In singleton pregnancies, the acceptance rate of genetic
      amniocentesis was 70.7% (58/82) in the IVF group compared to 77.9% (1837/2356) (P
      = 0.14) in the women who conceived spontaneously. The corresponding values in
      multiple gestation pregnancies were 71.1% (37/52) and 62.9% (34/54) respectively
      (P = 0.41). There was no difference in the acceptance rate of amniocentesis
      between singletons (70.7%) and multiple gestations (71.1%) after IVF (P = 0.96),
      while in women who conceived spontaneously, the acceptance rate of 78% in
      singletons was significantly higher than the acceptance rate of 63% in multiple
      gestations (P = 0.008). Adjusting for confounding variables, women with multiple
      gestations were about 40% less likely to accept genetic amniocentesis (OR = 0.63,
      95% CI = 0.39-1.00, P = 0.05), while women with a history of miscarriage were
      about 17% less likely to accept genetic amniocentesis (OR = 0.83, 95% CI = 0.68
      1.00, P = 0.05). Adjusting for multiple gestation and previous miscarriage, IVF
      was not independently associated with acceptance of genetic amniocentesis (OR =
      0.84, 95% CI = 0.54-1.29, P = 0.42). CONCLUSIONS: There is no difference in the
      acceptance rate of genetic amniocentesis among women with IVF pregnancies
      compared with those who conceive spontaneously, after adjusting for multiple
      gestation and previous miscarriage. Unlike women who conceive spontaneously, the
      decision to accept amniocentesis appears not to be influenced by the presence of
      multiple gestation in women with IVF pregnancies.

PMID- 12813767
TI  - Perinatal findings and molecular cytogenetic analysis of trisomy 16q and 22q13.3
      deletion.
AB  - OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis
      of a case with concomitant trisomy 16q and 22q13.3 deletion of paternal origin.
      CASE AND METHODS: A 24-year-old pregnant woman was referred at 30 weeks'
      gestation for suspected fetal abnormalities. Sonographic examination revealed
      decreased fetal movement, dolicocephaly, an asymmetric skull, and intrauterine
      growth restriction. Prenatal karyotyping was suggested but was declined. A female
      baby was delivered vaginally at 39 weeks' gestation with a body weight of 2180 g.
      The neonate presented generalized hypotonia with frequent apneic episodes and
      died at 1.5 months of age. Additional physical abnormalities included epicanthal
      folds, ptosis, frontal bossing with an enlarged metopic suture, bitemporal
      narrowing, hypertelorism, epicanthal folds, a pointed chin, micrognathia,
      prominent ears with preauricular pits, and clinodactyly. The karyotype from
      peripheral blood lymphocytes was 46,XX,der(22)t(16;22)(q12.1;q13.3)pat. The
      microdeletion at 22q13.3 was investigated by fluorescent in situ hybridization
      (FISH) analysis using the LSI DiGeorge/VCFS region/ARSA dual color DNA probe and
      the 22q telomeric probe, of which only the latter was able to detect the subtle
      deletion. Molecular analysis using polymorphic microsatellite markers indicated
      that the breakpoint at 22q13.31 was located between loci D22S1171 (present) and
      D22S1168 (absent). CONCLUSION: The use of LSI DiGeorge/VCFS region/ARSA dual
      color DNA probes to examine distal 22q would miss some subtle terminal deletions
      of 22q13. However, the use of 22q telomeric probes would detect these minute
      deletions. Fetuses having trisomy 16q and 22q13.3 deletion may prenatally
      manifest decreased fetal movement, dolicocephaly, an asymmetric skull, and
      intrauterine growth restriction and postnatally present generalized hypotonia
      with frequent apneic episodes.

PMID- 12813768
TI  - Prenatal diagnosis of congenital rubella infection in the second trimester of
      pregnancy.
AB  - OBJECTIVES: This case report describes the clinical presentation, diagnosis and
      management of a case of acute rubella infection in the second trimester. The
      complex issues of prenatal diagnosis of a congenital rubella infection are
      discussed. METHODS: A 30-year-old woman presented with a fine macular rash at 15
      weeks' gestation. Laboratory testing included maternal rubella-specific IgG and
      IgM detection (booking blood and acute-phase sample) together with measurement of
      IgG avidity. Prenatal diagnosis at 19 weeks (amniocentesis) and 23 weeks
      (amniocentesis and fetal blood) was done using a reverse-transcriptase polymerase
      chain reaction to detect rubella-specific RNA. The fetal blood sample was also
      tested for rubella-specific IgM. RESULTS: Maternal serological results confirmed
      an acute rubella infection at 15 weeks' gestation. Rubella-specific RNA and IgM
      were detected in the fetal blood taken at 23 weeks' gestation. However, no
      rubella RNA was detected in either of the amniotic fluid samples collected at 19
      and 23 weeks. CONCLUSION: In second-trimester rubella where risk of fetal damage
      is low, prenatal diagnosis can identify the rubella-infected fetus, allowing the
      parents to make a more informed decision about their options. The optimal sample
      for prenatal diagnosis is fetal blood as no rubella-specific RNA was detected in
      the amniotic fluid.

PMID- 12813769
TI  - Prenatal diagnosis of limb-body wall complex in early pregnancy using three
      dimensional ultrasound.

PMID- 12813770
TI  - Prenatal diagnosis of Dandy-Walker syndrome in early pregnancy presenting with
      increased nuchal translucency and generalized edema at 13 weeks of gestation.

PMID- 12813771
TI  - Prenatal diagnosis of right pulmonary agenesis associated with VACTERL sequence.

PMID- 12813772
TI  - Prenatal diagnosis of de novo partial trisomy Xq (Xq22.1-->qter) and terminal Xp
      deletion following sonographic detection of intrauterine growth restriction.

PMID- 12813773
TI  - Association of partial trisomy 9 (9pter-->q22.3) with corpus callosum dysgenesis,
      bilateral subependymal cysts, and ventriculomegaly.

PMID- 12813775
TI  - Personal safety and the abuse of staff in a Scottish NHS Trust.
AB  - BACKGROUND: An employer's 'duty of care' is enshrined in statute and common law.
      This responsibility extends to identifying areas of risk to employee's safety and
      emotional well being. OBJECTIVE: To identify the views of NHS staff on their
      safety and exposure to assault and other forms of abuse. DESIGN: A survey by
      questionnaire and semi-structured interview of the staff of an NHS Trust.
      SETTING: A large Scottish NHS Trust. SUBJECTS: All 5365 staff of the Trust.
      RESULTS: Two thousand two hundred and ninety four (43%) employees contributed to
      this survey. With regard to exposure to hazardous substances and serious
      infection, most staff were satisfied with safety standards and guidelines. Over a
      12 month period 23% of the workforce had been assaulted, mainly by patients and
      63% had experienced verbal abuse, again, mainly from patients. There were
      differences among occupational groups but overall 16% had been bullied; 18% had
      suffered discrimination; 22% had experienced harassment, and 13% had been
      victimized. Only 42% of individuals reported their most distressing incidents;
      56% of them regarded the outcome of their reports as satisfactory. CONCLUSIONS:
      Staff are generally satisfied with the steps taken to safeguard them against
      hazardous substances and serious infection. Assault by and abuse from patients is
      a considerable risk, especially for trained nurses. In terms of bullying,
      harassment, discrimination and victimization, the abuse of power by colleagues is
      also a distressing and under-reported phenomenon which needs to be addressed by
      regular audit and the creation of a climate in which employees feel secure enough
      to report such abuse and to have faith in the mechanisms set up to deal with such
      complaints.

PMID- 12813776
TI  - Neighbourhood cohesion and health in socially contrasting neighbourhoods:
      implications for the social exclusion and public health agendas.
AB  - OBJECTIVE: To report on perceived neighbourhood cohesion and describe its social
      distribution. DESIGN: Analysis of data from third wave of data collection from
      Localities component of West of Scotland Twenty-07 Study, collected in 1997 by
      postal survey. SETTING: Socially contrasting neighbourhoods in Glasgow City in
      the West of Scotland. SUBJECTS: Five hundred and ninety seven people (262 males,
      336 females), participants in a longitudinal study. RESULTS: Respondents who are
      older, live in owner-occupied houses in more affluent areas and who are not
      working outside the home report significantly more positive assessments of
      perceived neighbourhood cohesion. Sex, social class and family circumstances did
      not predict perceived neighbourhood cohesion. There were significant associations
      between neighbourhood cohesion and self assessed health in the last year; mental
      health using the GHQ12 measure; total number of symptoms reported in the last
      month; and reported number of 'malaise' or 'physical' symptoms after taking socio
      demographic factors into account. CONCLUSION: Lack of social cohesion may be more
      common in deprived areas in Scotland and may produce poorer mental health. Living
      in an area with low levels of social cohesion may be part of the pathway between
      life circumstances and death.

PMID- 12813777
TI  - The boom that never was: results of a 10 year audit of paediatric growth hormone
      prescribing in Scotland.
AB  - OBJECTIVE: To investigate trends in paediatric growth hormone (GH) prescribing in
      Scotland. DESIGN: Annual audit of paediatric GH patients, analysed by
      geographical distribution, diagnosis, age and duration of treatment, dosage, sex
      ratio and prescribing body. SUBJECTS AND SETTING: Paediatric patients receiving
      GH who attended the four tertiary referral centres in Scotland: Glasgow,
      Edinburgh, Dundee and Aberdeen, from 1990-1999. RESULTS: The annual total number
      of paediatric GH recipients ranged from 296-393. The maximum was recorded in
      1994, with a progressive decline thereafter. The latest total (296, 1999)
      represents a 19% decrease since 1990. There is a marked disparity between these
      figures and projections published by the Scottish Office Clinical Research and
      Audit Group (CRAG) in 1990 of 500 patients in 1995 and 600 by 2000. CRAG
      postulated that GH would prove efficacious in a wider range of conditions, that
      the number of survivors of childhood cancer would increase and that GH therapy
      would continue following clinical trials. While there has been a relative
      increase in oncology survivors during the 10-year period, the overall decline in
      numbers is largely attributable to familial short stature patients in whom there
      has been a five fold decrease, following completion of clinical trials of GH. The
      number of children classified "idiopathic growth hormone deficient" has also
      decreased, as the overlap between this condition and normal variant short stature
      is increasingly recognised. CONCLUSION: This expensive drug is being used
      relatively conservatively in Scotland, in the light of research experience. While
      a small degree of ad hoc usage is inevitable, we strongly support participation
      in national trials wherever possible. The adoption of an open approach with the
      Scottish Office regarding GH usage has proved beneficial in alleviating fear of
      escalating costs and preventing prescribing problems in a country in which 98% of
      GH is prescribed by general practitioners.

PMID- 12813778
TI  - A review of otolaryngology equipment provision in a peripheral clinic setting.
AB  - OBJECTIVE: To assess the adequacy of otolaryngology equipment provision in
      peripheral outpatient clinics. DESIGN: Prospective questionnaire study. SETTING:
      Five peripheral otolaryngology clinics in the Highlands of Scotland. (Thurso,
      Golspie, Dingwall, Fort William and Skye). SUBJECTS: All patients attending the
      above clinics over a six-month period. RESULTS: The questionnaire return rate was
      70%. 30% of patients may have had improved care had the equipment provision been
      adequate. Nine percent of patients required to be reviewed elsewhere due to
      inadequate equipment. The annual cost of these reviews exceeds 15,000 Pounds.
      CONCLUSION: The provision of adequate clinic equipment would have medium to long
      term economic advantages and also has relevance in relation to clinical
      governance and potential medico-legal concerns. The results of this review are
      timely as a recent BAO-HNS document has confirmed the equipment provision we
      describe above as being at the minimal acceptable level.

PMID- 12813779
TI  - Guardianship in the elderly and the Community Care Act: more of the same?
AB  - OBJECTIVE: Guardianship has been used in increasing numbers of elderly mentally
      disordered Scots in the past decade. During this time, the Community Care Act
      (CCA) encouraging the provision of care for individuals in their home has been
      enacted. This study aimed to see if the increased use of guardianship could be
      due to the use of orders to maintain at-risk elderly people in their homes.
      DESIGN: A retrospective survey of all new guardianship orders in people aged 65
      or over, comparing those in the two years before the CCA with those in the two
      years after. Cases were identified using the Mental Welfare Commission (MWC)
      database. MWC records for the individuals placed on guardianship were examined
      for data on demographics, social circumstances and perceived risks, together with
      duration and outcome of orders. Hospital case records were examined for
      diagnostic information. SUBJECTS: All individuals aged 65 or over placed on
      guardianship under the Mental Health (Scotland) Act 1984 between 1st April 1991
      and 31st March 1995. RESULTS: 85 new guardianship orders were identified, 22
      before and 63 after CCA. Most were female (82% before and 85% after) and suffered
      from organic mental disorders (82% before and 84% after). The modal duration of
      orders for both groups was six months with a trend towards longer orders being
      noted in the after CCA group. The majority of orders resulted in the placement of
      the individual in nursing or residential home care (82% before and after CCA).
      CONCLUSION: The increased use of guardianship in elderly mentally disordered
      individuals is not explained by the use of orders to maintain them at home. It is
      likelier that the process of social work assessment required by the CCA
      highlights more cases where guardianship could be used.

PMID- 12813780
TI  - Scottish Asthma Management Initiative.
AB  - OBJECTIVES: To describe the development process of a system that links audit,
      research and patient care and to detail the lessons learned from establishing a
      Scotland wide asthma management initiative. DESIGN, SETTING AND SUBJECTS: Health
      Boards and practices throughout Scotland were invited to participate in an
      initiative which links review of care, guideline implementation, chronic disease
      management (CDM) approval and post-graduate education for doctors (PGEA) and
      nurses (PREP). Participating practices were given the materials to review 30
      patients randomly selected from their asthma register. Health service resource
      use and drugs prescribed over a retrospective 12 month period were recorded for
      each patient using paper or electronic materials. All patients were invited for
      clinical assessment. RESULTS: A two-tier management system proved effective.
      Twelve of the 15 Scottish health authorities agreed to recognise the audit for
      automatic CDM approval although the negotiation process was prolonged; 566
      practices from all parts of Scotland have expressed an interest in the
      initiative. Provision of distance learning material linked to PGEA accreditation
      is free to general practitioners (GP's) and is a useful incentive for
      participation. To date 42 GPs have completed the distance learning element.
      CONCLUSION: The Scottish Asthma Management Initiative has provided the
      opportunity for all sectors of the health service in Scotland to work together to
      explore innovative ways to improve the management and care of chronic disease.
      Participation in an initiative linked to guidelines, education and CDM approval
      is an excellent way to facilitate health professionals to improve care.

PMID- 12813781
TI  - Respiratory morbidity in primary care. A population based study, using practices
      from the Scottish Continuous Morbidity Recording Research Database.
AB  - OBJECTIVE: To elucidate the patterns and period prevalences of respiratory
      disease with special reference to asthma (including wheezing) in view of its
      increasing reported prevalence. DESIGN: Observational study based on
      prospectively entered data. SETTING/SUBJECTS: Fifty five Continuous Morbidity
      Recording (CMR) practices with 290,000 patients located throughout Scotland.
      RESULTS: Respiratory problems accounted for a large proportion (17%) of total
      general practice workload. Upper respiratory tract infections were the commonest
      presentation in pre-school children, followed by asthma but with an ever
      increasing proportion of consultations for bronchitis and lower respiratory tract
      infections with advancing adult age. There was no significant correlation between
      deprivation and the incidence of asthma. CONCLUSIONS: Observed rates and patterns
      of disease for CMR practices, were similar to previously reported studies. The
      large number of presentations by patients in early childhood with minor
      respiratory illnesses and in particular upper respiratory tract infections are
      likely to reflect a heightened level of parental anxiety where interpretation of
      clinical signs and separation of simple and significant illness can be difficult.
      CMR has also been shown to be of use in helping to investigate links between
      deprivation and disease incidence or severity. Potential uses for CMR include the
      study of whole population morbidity and utilisation of primary care services.

PMID- 12813782
TI  - Medical and dental staffing in the health service in Scotland in 1999.

PMID- 12813783
TI  - Uptake of influenza vaccination and the reasons for non-vaccination in the high
      risk patients of Angus, Scotland.
AB  - OBJECTIVE: To ascertain the uptake of influenza vaccination, the main prompts to
      vaccination and the reasons for non-vaccination in the high-risk patients of
      Angus, Scotland. DESIGN: Prospective questionnaire survey. SETTING: A small rural
      district general hospital. SUBJECTS: General medical inpatients and outpatients.
      RESULTS: The overall uptake of vaccination was 44.8% (n = 250). The main prompts
      to vaccination were general practitioners (48.2%), the media (11.6%), practice
      and district nurses (8.9%), friends and relatives (8.9%) and posters at health
      centres and chemists (7.1%). The main reason for non-vaccination was a lack of
      awareness of high-risk status (50.7%). CONCLUSION: The uptake of influenza
      vaccination in the Angus region of Scotland is unsatisfactorily low. This is
      mostly due to a lack of knowledge regarding high-risk status, although other
      reasons, including concerns about the side effects of vaccination, are also
      important.

PMID- 12813784
TI  - A regional approach to the 'problem' of secondary prevention of coronary heart
      disease in Tayside.

PMID- 12813785
TI  - Impact of a nurse led multidisciplinary team on an acute medical admissions unit.
AB  - OBJECTIVE: To determine the impact of a nurse-led multi-disciplinary team on
      management of elderly patients with functional problems admitted to an acute
      medical admission unit. DESIGN: Data collection from the first 16 months of the
      team's operation. SETTING: A district general hospital, Scotland. SUBJECTS: All
      elderly patients with functional problems who were considered fit for immediate
      multi-disciplinary assessment. RESULTS: Over 1000 patients were assessed during
      the first 16 months. Twenty four per cent of these frail individuals were
      discharged directly home, of whom, almost half had some form of ongoing support.
      The remaining 76% were transferred for ongoing care to other wards in the Medical
      Directorate. Of this group, 49% moved to general medicine, 43% to geriatric
      assessment and 8% to the Stroke Unit. The team were perceived to improve the
      appropriateness of these transfers by enabling staff to review both the medical
      and functional needs of elderly patients when deciding on the best setting for
      ongoing care. CONCLUSIONS: Immediate multi-disciplinary assessment of elderly
      patients admitted to a medical admissions unit enables the early supported
      discharge of a proportion of elderly and enhances the ability of the hospital to
      place appropriately those patients requiring a longer stay.

PMID- 12813787
TI  - Recent announcement by the Food Standards Agency concerning its target to reduce
      food poisoning by 20% by 2006.

PMID- 12813788
TI  - National Services--the role of the National Services Division of the Common
      Services Agency in commissioning specialist services on behalf of the NHS in
      Scotland.
AB  - The National Services Division of the Common Services Agency provides a central
      function commissioning designated national services on behalf of the NHS in
      Scotland. Services are nationally designated and commissioned only where it would
      not be possible or sensible to do so on a more local basis because of the rarity
      of the condition, the need to concentrate expertise and/or to avoid duplication
      of expensive equipment. The Division also has important central functions in
      ensuring the effective delivery of national screening programmes and in
      facilitating the development of national managed clinical networks. The work
      programme of the Division is overseen by advisory bodies whose membership
      reflects the key stakeholders in the Scottish NHS. In discharging its role, the
      Division's aim is to work with clinicians and managers to ensure the delivery of
      high quality specialist clinical care and screening services in an equitable
      fashion to patients throughout Scotland.

PMID- 12813789
TI  - An examination of the role of clinical psychology in meeting the needs of young
      disabled clients and their families/carers.
AB  - This paper examines the views of clients with a physical disability, general
      practitioners and staff working in health and social work physical disability
      services about the needs of young disabled people. The most common area of
      disability seen by GPs was respiratory, followed by cardiac problems and stroke.
      With the exception of cardiac patients a third to over half of GPs felt that the
      needs of the identified groups were not being adequately met, in particular the
      needs of individuals with progressive neuromuscular problems. Over a quarter of
      clients felt that their needs were not being adequately met. Ninety-five percent
      of GPs and 100% of staff identified psychological needs of clients. For clients
      themselves, physical needs are ranked highest, with over 33 percent identifying
      psychological problems, 50 percent neuropsychological problems and 25 percent
      psychosexual difficulties as priority needs. In relation to carers, over 90
      percent of GPs, 100% of staff and 50 percent of clients highlighted psychological
      needs. The majority of participants felt that clinical psychology had an
      important role to play in physical disability services. There was broad agreement
      on the areas of need which psychology would be seen to address. These were
      psychological needs, behavioural problems, neuropsychological problems and
      relationship/psychosexual difficulties. A high percentage of both staff and GPs
      also saw a role for clinical psychology in meeting the psychological,
      relationship and psychosexual needs of carers.

PMID- 12813790
TI  - Care management in three practices--scope for improvement?
AB  - OBJECTIVE: The process of assessment of older people for residential/nursing home
      care may take place by hospital based social workers, or by care managers working
      in the community. We sought to compare the assessment process in each setting.
      The standards for the audit were that the data collection for both groups was
      equivalent, that both groups had a multi-disciplinary assessment, and that
      outcomes in both settings were appropriate. DESIGN: Identification of all older
      people assessed as requiring residential/nursing home care from 1/7/97-31/12/97,
      who were registered with the three general practices in Aberdeen participating in
      this study. Social Work case files and care plans were reviewed. All individuals
      were visited and dependency scores obtained--Abbreviated Mental Test, Barthel
      Index, and CAPE (Clifton Assessment Procedures for the elderly--Behaviour Rating
      Scale component) score. SETTING: Review of hospital social work case files, and
      community based case files. Interviewing of the older person in their own home,
      hospital, residential or nursing home to obtain dependency scores. SUBJECTS:
      Thirty three people were referred-17 from the community, and 16 from hospital.
      RESULTS: Case files in both groups were well maintained. There were differences
      in procedures between the assessment processes, but outcomes appeared to be
      similar. There was no statistical difference in mean dependency scores between
      each group. However, information on levels of support in the files was limited,
      particularly for the community group. Dependency scores correlated with
      residential/nursing home care being appropriate for the 33 individuals, but only
      50% of people were identified as wanting such arrangements. Evidence of a
      recorded medical assessment was absent in 47% of the community referred
      population. CONCLUSION: Evidence of a multi-disciplinary assessment was not
      always available, especially for the community referred individuals. A greater
      emphasis on a multi-disciplinary assessment could highlight a need for
      rehabilitation, which might allow for the improvement and maintenance of some
      frail older people in the community, this often being in accordance with their
      wishes.

PMID- 12813791
TI  - Effect of general practitioner hospitals on district general hospital bed use in
      the Highlands of Scotland.
AB  - OBJECTIVE: To examine hospital bed use by General Practices with and without
      access to General Practitioner beds. DESIGN: Information from the Contract
      Management System for General Medicine and Surgery, and from SMR returns for
      Geriatric Medicine and GP beds was used to compare hospital bed use in District
      General Hospitals (DGHs) and in General Practitioner beds for practices with and
      without access to GP beds. Age adjusted rates were calculated for overall use of
      each specialty. SETTING: All General Practices in the Highland Health Board area
      for December 1995-April 1997. RESULTS: Compared to practices with no access to GP
      beds, practices with access used 39.4% fewer bed days per 1000 patients for
      medical specialties; 18% fewer bed days for surgical specialties; 34.5% fewer bed
      days for geriatric medicine, and 4.9% fewer bed days for other DGH specialties.
      Taking into account GP bed day use, practices with access to GP beds used 6.1%
      more hospital bed days per 1000 patients than did practices with no access.
      CONCLUSION: These findings largely replicate work in England that found
      substantial decreases in General Medical and Geriatric Medicine bed use in
      Practices with access to GP beds, combined with an overall increase in occupied
      bed day use of 6-8% per 1000 patients. The lower use of surgical beds was
      unexpected, and may reflect more flexible use of GP beds in the Highlands for
      observation or rehabilitation, possibly related to the far greater distances
      involved than in the English studies.

PMID- 12813792
TI  - An audit of the vaccination and antibiotic prophylaxis practices amongst patients
      splenectomised in Lothian.
AB  - OBJECTIVE: To evaluate current post-splenectomy immunisation and antibiotic
      prophylaxis practices amongst patients splenectomised in Lothian between 1st
      January 1989 and 31st December 1997. DESIGN: Retrospective cross-sectional study
      of the general practitioners of patients recorded as having had a splenectomy
      operation. SETTING: Lothian Health Board (population 771,000). SUBJECTS: Asplenic
      patients recorded on Scottish Morbidity Records as having had a splenectomy in
      Lothian between 1st January 1989 and 31st December 1997. RESULTS: Eighty point
      six percent of the patients were vaccinated against Streptococcus pneumoniae,
      65.9% were vaccinated against Haemophilus influenzae, and 48.2% were vaccinated
      against Neisseria meningitidis; 74.8% of patients were being prescribed long-term
      antibiotic prophylaxis. However, only 37.4% were both vaccinated and prescribed
      prophylaxis as recommended, in Department of Health guidelines. CONCLUSIONS: The
      vaccination levels seen in this survey are higher than levels reported in
      previously published surveys in the UK. Reported rates of post splenectomy
      vaccination against S. pneumoniae in both the UK and North America in 1993 ranged
      from 10% to 36%. However, there still remains a substantial proportion of
      splenectomised patients in Lothian, including some of those with the highest risk
      of infection, who are not vaccinated or prescribed prophylaxis as recommended.

PMID- 12813793
TI  - Prioritisation of research recommendations from a national needs assessment
      programme.
AB  - OBJECTIVE: To gain consensus on and rank research and development recommendations
      from a series of Scottish Needs Assessment Programme (SNAP) reports. DESIGN: A
      two stage Delphi questionnaire was used and participants were asked to rank the
      recommendations in terms of potential health gain, practicality and priority.
      SUBJECTS: Views were sought from all consultants in dental public health in
      Scotland and from non-consultant members of the SNAP oral health steering group.
      RESULTS: Of the 17 individuals eligible, 16 participated in the study. Fifty four
      recommendations for research and development were identified in seven SNAP
      reports. Recommendations relating to the prevention of dental caries in young
      children, the organisation and delivery of dental care to disadvantaged groups
      and increased understanding of the aetiology and pathogenesis of oral cancer in
      younger people were seen as of highest priority. CONCLUSIONS: This study has
      drawn together and prioritised a series of recommendations, and will help inform
      future oral health research needs in Scotland.

PMID- 12813794
TI  - Supporting staff in employment: the emotional wellbeing of staff in an NHS
      psychiatric hospital.
AB  - OBJECTIVE: The objective of this study was to assess the emotional wellbeing of a
      broad sample of NHS employees in a psychiatric setting; to seek their views on
      sources of distress; and to identify preferred ways of dealing with it. DESIGN: A
      cross-sectional postal survey, employing two questionnaires: GHQ-28, and a semi
      structured questionnaire. These were sent to a nominal 50% sample (n = 599).
      SETTING: The population was the staff of a large Scottish psychiatric service.
      RESULTS: A 47.9% response rate was achieved; 32.9% of respondents exceeded a cut
      off score of four on the GHQ-28. Neither occupational, group nor gender effects
      were significant on this measure. The reporting of emotionally-distressing
      problems affecting their performance was found to be more common amongst doctors;
      males, overall, showed a non-significant trend towards having been affected more
      than females by such problems; and older staff (above 45) were affected
      significantly more often than younger staff. Almost a third of staff were unaware
      of the availability of an internal organisational resource (the Occupational
      Health service). CONCLUSION: NHS Trusts should ensure the culture at work is
      appropriate from a preventative point of view and be aware that factors outwith
      the workplace can affect employees emotional wellbeing and performance.
      Preventative and supportive measures to minimise psychological distress in the
      workforce should be considered; the Scottish Needs Assessment Programme: Mental
      Health in the Workplace offers useful guidance.

PMID- 12813795
TI  - Incidence, hospital admission rate, and health outcomes following stroke in
      Ayrshire and Arran.
AB  - OBJECTIVE: To describe the incidence, hospital admission rate and health outcomes
      following stroke in Ayrshire and Arran. DESIGN: Community based study with
      prospective identification of stroke patients from a random sample of general
      practices stratified by geographical area and practice size. SETTING: Ayrshire
      and Arran Health Board area, West of Scotland. SUBJECTS: All stroke patients from
      the 24 general practices in the sample. MAIN OUTCOME MEASURES: Barthel Index,
      Canadian Neurological Scale, Mini-mental State Examination, SF-36. RESULTS: The
      incidence of stroke was 2.33 per 1000 for both first and recurrent events and 78%
      of people were admitted to hospital following their stroke. Those admitted to
      hospital had significantly poorer outcomes in the early post-stroke period (first
      six months). CONCLUSION: Our study provides recent figures for the incidence and
      hospital admission rates following stroke. We speculate that our rates may be
      typical for the NHS in Scotland at present.

PMID- 12813796
TI  - Audit can ensure the safe and effective introduction of seizure prophylaxis with
      magnesium sulphate in obstetric practice.
AB  - OBJECTIVE: To audit the effectiveness and safety of intravenous magnesium
      sulphate therapy in severe pre-eclampsia. DESIGN: A complete audit cycle
      including the first eight cases receiving therapy, an intervention with staff
      instruction and the re-audit of eight further consecutive cases. The issues for
      audit were compliance with the protocol and the achievement and maintenance of
      therapeutic magnesium concentrations. SETTING: Labour room, Glasgow Royal
      Maternity Hospital. SUBJECTS: Women with severe pre-eclampsia fulfilling pre
      determined criteria for seizure prophylaxis with intravenous magnesium therapy.
      RESULTS: Protocol violations resulted both in delays in achieving therapeutic
      magnesium concentrations and high magnesium concentrations in five of the eight
      initial cases. Following circulation of the results and staff education, the re
      audit demonstrated near complete compliance with the protocol and a more
      consistent interval to achieving a therapeutic magnesium concentration. There
      were no cases of eclampsia or magnesium toxicity amongst women delivering at GRMH
      during the period of this audit. CONCLUSION: This audit has demonstrated that
      seizure prophylaxis with intravenous magnesium sulphate can be safely and
      effectively introduced to the obstetric management of women with severe pre
      eclampsia.

PMID- 12813797
TI  - Rural relocation and clinical psychology referrals.

PMID- 12813798
TI  - Unmet need in osteoporosis.
AB  - OBJECTIVE: To audit the management of females presenting to Accident and
      Emergency department with a diagnosis of low impact Colles fracture. DESIGN:
      Telephone questionnaire of 50 patients who attended A & E in 1998 with diagnosis
      of Colles fracture SETTING: Glasgow Royal Infirmary within North Glasgow
      catchment area. SUBJECTS: Women between 45-79 years of age who attended Accident
      and Emergency Department in 1998 with a diagnosis of low impact Colles fracture.
      RESULTS: Mean age was 63 years (range 44-78): ninety percent were post menopausal
      and 40% of the total group were smokers. Twenty six percent had a positive family
      history of osteoporosis, 24% had undergone hysterectomy and 88% took no part in
      any load bearing exercise. Ten percent (n = 5) were on treatment (1 alendronate,
      3 etidronate with calcium, 1 hormone replacement therapy) CONCLUSION: A
      significant proportion of our study population have multiple risk factors for
      osteoporosis which are not being addressed. Raising awareness in orthopaedic
      surgeons, family doctors and patients is urgently required.

PMID- 12813799
TI  - Research priorities in primary care. A report from the CSO's primary care
      implementation committee.

PMID- 12813800
TI  - Closing the health gap--a challenging opportunity.

PMID- 12813801
TI  - Tackling health inequalities--rhetoric or reality?

PMID- 12813802
TI  - Addressing inequalities in health--possible interventions in primary care.

PMID- 12813803
TI  - Health inequalities.

PMID- 12813804
TI  - Scottish Medical and Scientific Advisory Committee.

PMID- 12813805
TI  - The Scottish Programme for Clinical Effectiveness in Reproductive Health
      (SPCERH): lessons from a three-year programme.
AB  - OBJECTIVE: To describe the work of the Scottish Programme for Clinical
      Effectiveness in Reproductive Health (SPCERH) in order to draw lessons applicable
      to other clinical effectiveness programmes. DESIGN: Overview of an integrated
      clinical effectiveness programme relating to reproductive health. SETTING:
      Scotland. SUBJECTS: The programme is designed to reach all professionals who
      share responsibility for reproductive healthcare--including
      obstetrician/gynaecologists, midwives, general practitioners, family planning
      doctors, commissioners of services and NHS managers. RESULTS: During its first
      three-year Workplan, SPCERH has conducted an integrated programme of audit,
      guideline and educational activities. Findings have been disseminated using multi
      faceted approaches including publications, presentations and interactive
      meetings. Evidence from surveys undertaken within the Programme indicates that
      clinicians have changed or reconsidered their practice in several key areas in
      response to audit and guideline recommendations made by the Programme.
      CONCLUSIONS: As a way of funding and organising clinical effectiveness
      activities, the integrated Programme has many advantages over the stand-alone
      Project. These advantages include: enabling the linkage of national audits to
      national guidelines and other forms of NHS guidance; enabling the re-audit of
      topics after a time interval sufficient to allow for the implementation of
      change; the building of expertise within a dedicated team and the use of that
      expertise across a range of linked projects; the availability of an experienced
      team which can respond to new priority issues at short notice.

PMID- 12813806
TI  - Survey of the late consequences of polio in Edinburgh and the Lothians.
AB  - OBJECTIVE: This study aimed to identify the nature and frequency of new symptoms
      and associated disabilities experienced by people who suffered poliomyelitis many
      years ago, and their access to hospital services. DESIGN: Postal survey regarding
      symptoms, disability (Office of Population Censuses & Surveys (OPCS) disability
      questionnaire), and experience of services. SUBJECTS & SETTING: People known to
      the British Polio Fellowship and the regional rehabilitation service who had
      previously had polio and were resident in Edinburgh and the Lothians. RESULTS:
      The study population of 125 people had a median age of 59 years, and 60% were
      female. The most common symptoms, present in over 60%, were: cold intolerance,
      fatigue, increased and new muscle weakness, muscle and joint pain, and sleep
      disturbance. Motor disabilities, particularly of lower limbs, were prominent.
      Patient contact with hospital services in the preceding five years was: clinic
      (62%); physiotherapy (46%); occupational therapy (29%); speech therapy (2%);
      wheelchair service (42%); orthotics (40%). CONCLUSIONS: New problems are
      sufficiently frequent and severe to warrant a more detailed study to quantify the
      health care requirements of the post-polio population.

PMID- 12813807
TI  - Improving care or professional advantage? What makes clinicians do audit and how
      well do they fare?
AB  - OBJECTIVE: To find out why clinicians undertake audit, the extent to which they
      complete the process of audit and their perception of the benefits of taking
      part. DESIGN: Semi-structured interviews. SETTING: Twelve trusts in three
      Scottish Health Boards. SUBJECTS: One hundred and forty five respondents of
      different status from a wide range of clinical specialities. RESULTS: Sixty six
      per cent of respondents defined clinical audit as a means of making changes with
      a view to improving care, but 62% reported the purpose of audit as the
      examination of the usefulness of treatment or the observation of practice.
      Personal reasons for taking part included justifying practice (32%) and as a
      means of professional development (15%). Twenty one percent held formal minuted
      meetings, the majority were informal. Sixty six percent of clinicians completed a
      project plan but pilot studies (49%) and re-audits (26%) were less common. Twenty
      four percent changed practice as a result of the audit. The extent to which the
      audit process had been completed predicted clinicians' ability to make changes.
      CONCLUSION: Clinicians' understanding of the concept of audit was not translated
      into practical projects. The main reasons for this are the organisational
      difficulties clinicians are faced with when carrying out audit and a lack of
      attention to all parts of the audit process. Despite this failure to achieve
      change, many clinicians felt they had benefited from their experience of audit.
      Management should appeal to these motivations of employees and provide a culture
      which enforces their importance over and above changing practice.

PMID- 12813808
TI  - Gastrointestinal infections presenting in general practice in Scotland.
AB  - OBJECTIVES: To determine the incidence of gastrointestinal infections (GII)
      presenting to general practitioners (GPs) in Scotland, To record the demographic
      and clinical characteristics of persons presenting with GII, To determine the
      proportion and characteristics of GII investigated in the laboratory, To report
      on the microbiological aetiology of the GII. DESIGN: Descriptive epidemiological
      study. SETTING: Twenty three general practices in Scotland serving a total
      practice population of 152,471. SUBJECTS: Patients consulting their GPs for a
      'gastrointestinal infection' which met the study case definition. RESULTS: These
      are presented for the 3872 patient consultations for GII between April 1996 and
      December 31st 1997 which met the survey case definition. The crude annual rate of
      new consultations recorded was 1.7 per 100 person years. The crude monthly
      consultation rate for new cases ranged between 11 and 18 per 10,000 patients. GPs
      notified 9% of the cases as 'food poisoning'. A request for microbiological
      testing of samples at the local laboratory for clinical reasons was documented
      for 34% of cases with diarrhoea. The study laboratory received faecal samples by
      post from 66% of these cases. About one in five of the samples tested revealed
      evidence of infection with a common gastrointestinal pathogen. The pathogens most
      frequently reported were Campylobacter sp and Salmonella sp. CONCLUSION: The
      incidence of consultations for GII in Scotland is similar to that recorded in a
      recent survey in England. The very low notification rate by GPs means that
      statutory notification by telephone or post is a poor basis for early warning of
      outbreaks. It is recommended that a pilot study of electronic notification using
      the NHS net is set up.

PMID- 12813809
TI  - Trying to understand routine stroke outcome data: the need for adequate casemix
      adjustment and some practical considerations.
AB  - OBJECTIVE: To determine how far the difference in published stroke case fatality
      between the Western General Hospital (WGH), Edinburgh and the Falkirk and
      District Royal Infirmary (FDRI) for the period 1990-93 can be explained by
      adjusting more fully for casemix. DESIGN: The cases were ascertained and followed
      prospectively at the WGH and retrospectively at the FDRI; casemix correction was
      performed using a validated logistic regression model. SETTING: The WGH is a
      teaching hospital and the FDRI a district general hospital. SUBJECTS: Four
      hundred and thirty seven patients with a verified acute stroke at the WGH; 471
      patients assigned a cerebrovascular disease discharge diagnostic code at the
      FDRI. OUTCOME MEASURE: Thirty day case fatality. RESULTS: About half of the
      difference in the two hospitals' published stroke case fatality could be
      accounted for by variation in measured casemix. The residual difference in
      adjusted case fatality might have been due to differences in the structure of
      stroke care or simply to remaining differences in casemix. Full investigation of
      the cause was prevented by the destruction of the deceased patients records.
      CONCLUSIONS: Comparisons of routinely collected stroke outcomes will remain
      difficult to interpret unless casemix is properly accounted for and deceased
      patients' records stored for several years.

PMID- 12813810
TI  - The impact of highly active antiretroviral combination therapy in HIV infected
      patients in Glasgow.
AB  - OBJECTIVE: To assess the impact of treatment with highly active antiretroviral
      therapy on morbidity and mortality in the HIV infected population in Glasgow.
      DESIGN: Retrospective analysis of the HIV clinical and pharmacy databases in a
      Department of Infectious Diseases, the major provider of HIV treatment and care
      in Glasgow. SUBJECTS AND SETTING: The study population comprised all HIV infected
      individuals who attended the Department of Infectious Diseases as inpatients or
      outpatients from April 1994 to March 1999. The main outcome measures were the
      number of deaths; the number of new AIDS diagnoses; expenditure on drugs for the
      treatment or prevention of opportunistic infections; hospital admissions of HIV
      patients; and occupied bed days. RESULTS: The number of patients attending in
      each year was 215 in 1994-95, rising to 242 in 1998-99. During the same time
      period there was a 75% reduction in the number of deaths (36 in 1994-95 falling
      to 10 in 1998-99) and the number of AIDS diagnoses (28 to 7), and a 50% reduction
      in occupied bed days (3,278 to 1,676) and hospital admissions of HIV infected
      patients (328 to 164). This occurred at a time when antiviral drug therapy for
      HIV infection shifted from monotherapy to dual therapy and subsequently to triple
      or quadruple therapy. In the last two years of the study the majority of treated
      patients were on a three or four drug regimen. CONCLUSION: Between 1994 and 1999
      there was a marked reduction in the morbidity and mortality of the HIV infected
      population in Glasgow. This was most likely due to the introduction and
      widespread use of highly active antiretroviral drug therapy.

PMID- 12813811
TI  - Life expectancy calculations for postcode sectors and their use for monitoring
      inequalities in the nation's health.
AB  - OBJECTIVE: To describe how life expectancy calculations can be used to
      demonstrate differences in mortality between populations of different
      socioeconomic status at each population census. DESIGN: Population data were
      obtained in five-year age-sex and deprivation groups at postcode sector level for
      the Greater Glasgow Health Board area for the censuses of 1981 and 1991. The
      numbers of deaths for the same groups were obtained for the three-year periods
      1980-82 and 1990-92. Life expectancy tables were derived by applying mortality
      rates calculated from these data to a synthetic cohort of individuals. Regression
      analyses were applied to the tables thus derived to examine the relationships
      between census period, level of deprivation and life expectancy. RESULTS: Over
      the period 1980/82 to 1990/92 life expectancy of the age group 0-4 years
      increased by 2.1 years in males and 2.9 years in females, increases being greater
      in the more affluent areas. Differences in life expectancy between the
      geographically defined most deprived and most affluent areas increased from 7.4
      to 9.0 years in males and from 5.9 to 6.0 years in females. CONCLUSION: Life
      expectancy is increasing in all socioeconomic groups, but particularly in the
      most affluent. We suggest that life expectancy values should be published
      routinely for different socioeconomic groupings. Over time these would illustrate
      more clearly the relationships between health policy and health outcomes, and
      would demonstrate whether policies are reducing inequalities and generally
      improving health.

PMID- 12813812
TI  - Do diabetes guidelines influence the content of referral letters by general
      practitioners to a diabetes specialist clinic?
AB  - OBJECTIVE: To ascertain whether local guidelines for diabetes management
      influence the content of GP referral letters to a diabetes specialist clinic.
      DESIGN: Retrospective survey of hospital outpatient clinic casenotes and GP
      referral letters of patients with Type 2 diabetes. METHODS: An examination was
      made of 200 GP referral letters submitted before (Set 1), and 200 GP referral
      letters submitted after (Set 2), local guidelines on the management of adult
      diabetes had been issued to GPs in Lothian. The frequency with which micro- and
      macrovascular complications of diabetes were documented in the GP referral
      letters was compared with the frequency ascertained at the first attendance to
      the specialist clinic. MAIN RESULTS: Following the distribution of diabetes
      guidelines, no significant change was noted in the frequency with which specific
      conditions were documented in GP referral letters (Set 1 vs Set 2): hypertension
      (72% vs 79%); cerebrovascular disease (89% vs 80%); ischaemic heart disease (74%
      vs 79%); peripheral vascular disease (42% vs 64%); cataract (35% vs 44%);
      retinopathy (18% vs 40%) and peripheral neuropathy (17% vs 12%). At the diabetic
      clinic many unreported diabetic complications were found in patients who had been
      referred after varying periods of treatment in primary care. However, the
      guidelines did appear to have encouraged the active treatment of hyperglycaemia
      by GPs before referral of newly-diagnosed diabetic patients. CONCLUSIONS:
      Diabetes guidelines per se appeared to have very little effect on increasing the
      information provided in GP referral letters on relevant medical problems and did
      not appear to have influenced screening for complications in patients with Type 2
      diabetes by GPs before specialist referral. Methods other than the issue of
      written guidelines are required to achieve optimal assessment of diabetic
      patients in the community.

PMID- 12813813
TI  - Food poisoning notification: time for a rethink.
AB  - The notification of food poisoning is a statutory obligation of medical
      practitioners in the United Kingdom. Its objectives and methods are vague and ill
      documented, and the value of its output doubtful. Statutory notification of food
      poisoning is poor at identifying outbreaks, or single cases of severe disease, or
      as a measure of longer term trends. It should be fundamentally reformed.

PMID- 12813814
TI  - Determinants of survival in continuing care settings.
AB  - OBJECTIVE: To assess the relationship between the Barthel Index, a widely used
      assessment measure of physical dependency, and long-term survival in continuing
      care settings. DESIGN AND SUBJECTS: One hundred and eighty five older people
      moving into continuing care (hospital or nursing home) were prospectively
      assessed with regard to physical and mental impairment in 1991/2 and this
      population was followed up in 1996. RESULTS: In addition to the 185 patients who
      were assessed, there were 41 patients who died before they could be seen. Out of
      the total of 226 patients, 177 had died by the time of the census point in 1996.
      Multivariate (Cox regression) analysis of survival in the 185 patients indicated
      that only the Barthel Index (BI) and female sex were statistically significantly
      related to survival rates. Those with a BI of 12-20 had better survival than
      those with a BI of 7-11 (P = 0.015) or a BI of 0-6 (P = 0.007). CONCLUSIONS: The
      importance of careful assessment of those moving into continuing care settings is
      emphasised. Those patients who are physically less dependent are likely to have
      significantly longer survival periods and related use of continuing care
      resources.

PMID- 12813815
TI  - Mums on Prozac, kids on inhalers: the need for research on the potential for
      improving health through housing interventions.
AB  - In a short term qualitative study exploring the impact that improvements to
      housing might have upon the health of household members, respondents perceived
      significant benefits of housing improvements for physical and mental health, and
      for both children and adults. There is a need for prospective research which
      monitors health and wellbeing before, during, and after housing improvement and
      which uses independent measures of health.

PMID- 12813816
TI  - Influence of biological, behavioural, health service and social risk factors on
      the trend towards more frequent.
AB  - OBJECTIVES: To analyse the trend in rising acute hospital admission rates in the
      Renfrew Paisley MIDSPAN cohort and assess the influence of baseline risk factor
      data, morbidity patterns, deprivation category and characteristics of GP practice
      on the increase. DESIGN: Cohort analysis which, using a linked data set covering
      a 23 year follow-up period, combined original 'risk'-related data with subsequent
      routine hospital admissions data. A multiple logistic regression model predicted
      changes in hospital admissions patterns. SETTING: Renfrew and Paisley, two post
      industrial towns in Scotland. SUBJECTS: Eight thousand three hundred and fifty
      four women and 7,052 men, aged 45-64 in the early 1970s. MAIN OUTCOME MEASURES:
      The contribution that each of the factors investigated made to the likelihood of
      admission over time. RESULTS: While risk status in middle life, diagnosis reached
      after admission, deprivation category and characteristics of GP practice
      influence the absolute chance of being admitted to hospital, changes in these
      factors do not explain much, if any, of the quite marked increase in admission
      rates observed during the last 10 year of the follow-up period. CONCLUSIONS:
      Whatever the reasons for the trend of rising admission, the most likely
      explanation appears to be a combination of social and health service related
      factors. For the Paisley-Renfrew cohort, factors like smoking status, FEV1,
      deprivation category and GP practice remain important predictors of admission
      throughout the time period but changes in these factors explain little of the
      rising trend in admissions.

PMID- 12813818
TI  - "Failure of emergency out-patient appointments to reduce admission rates". Health
      Bulletin 2000;58(2): 112-117.

PMID- 12813819
TI  - Thinking ahead--the importance of exit strategies to successful implementation of
      clinical effectiveness initiatives.
AB  - The Clinical Resource and Audit Group (CRAG) remains the focus for the
      development of clinical effectiveness with particular emphasis on strategic
      alignment and implementation. CRAG believes that early consideration and planning
      of exit strategies is essential to deliver successful dissemination and
      implementation of clinical effectiveness initiatives. Open sharing of results in
      encouraged, with due consideration of the challenges of presenting information
      fairly and clearly to avoid misinterpretation, particularly for the lay public.
      Valuable lessons from effectiveness initiatives should be shared widely and
      introduced quickly into normal clinical practice, releasing effectiveness
      resources for new challenges. CRAG will produce guidance to support the
      development of exit strategies later in the year; comments and contributions are
      welcome.

PMID- 12813820
TI  - A review of an outpatient paediatric mental health clinic: what we did and what
      parents thought of it.
AB  - OBJECTIVE: To describe the work of a paediatric mental health (PMH) clinic in
      terms of the types of clients seen and the nature and intensity of interventions
      used. Also to survey the opinions of parents on issues such as helpfulness and
      effectiveness, and to tap into issues relating to acceptability and relevance.
      DESIGN: Retrospective review of case notes covering a one year period and postal
      client satisfaction questionnaire. SETTING: Children's wing of a large general
      hospital. SUBJECTS: The case notes of the 54 children referred were analysed.
      Postal questionnaires were sent to 53 parents of the 41 children who were treated
      over the targeted 12 months plus a further 12 families who were treated in the
      six months following. RESULTS: Forty one children with a broad range of
      paediatric difficulties were treated with their parents. Families were seen
      relatively promptly after referral and interventions were typically brief
      involving advice and counselling for parents and most commonly behavioural work
      with children. The results from the parent satisfaction questionnaire suggested
      that despite some initial wariness and uncertainty, parents found the clinic to
      be helpful. A small, but non significant decrease in rated symptom severity was
      found following treatment, but even in those cases where symptoms persisted or
      increased, parents still tended to report their experience as being helpful and
      from their comments seemed to value the clinic. Although parents seemed somewhat
      intimidated and uncertain of its relevance before attending, their comments
      suggested that they had benefited from talking about their child's difficulties
      and gaining understanding within a supportive and friendly environment.
      CONCLUSIONS: The PMH clinic was found to provide a brief, focused intervention
      for children and their families which was regarded as helpful by parents, even
      when the outcome was not necessarily a reduction in symptom severity.

PMID- 12813821
TI  - Illicit drug use related attendances at accident and emergency services in
      Aberdeen: a prospective six month survey.
AB  - OBJECTIVE: To quantify and examine the nature of known illicit drug related
      attendances at the Accident and Emergency Department of Aberdeen Royal Hospital
      over a six month period. DESIGN: A structured questionnaire was completed by
      Accident and Emergency staff. SETTING: The Accident and Emergency Department of
      Aberdeen Royal Hospital. SUBJECTS: All patients presenting at the Accident and
      Emergency Department as a result of known illicit drug use between November 1996
      to April 1997 inclusive. RESULTS: One hundred and fifty seven subjects presented
      at Accident and Emergency during the six month period. Peak attendance was
      between 18.00 and 21.00 hours. Twenty seven percent of patients chose to visit
      Accident and Emergency rather than their own general practitioner. Thirty seven
      percent had no involvement with any health care professional regarding their drug
      use. Heroin was used by 62% of cases of which the majority (94.9%) had injected
      and stimulants such as amphetamine and ecstasy were used by a large proportion of
      cases. Only 4.5% of subjects admitted to not using clean equipment yet 15%
      admitted to have loaned equipment (to someone else) and 22% of subjects had
      injecting related problems. Thirteen percent of subjects were considered unco
      operative by staff. Fifty four percent of subjects required admission to a ward
      and ten patients (6%) died. CONCLUSION: Heroin continues to be the main drug
      causing major health problems. Harm reduction messages are not adequately
      reaching/or being taken up by drug users given the high proportion with injecting
      related problems and those being prepared to lend needles. The receptive attitude
      amongst subjects highlighted the opportunity for patient education as well as
      giving contact addresses of relevant organisations.

PMID- 12813822
TI  - Out-patient psychodynamic psychotherapy services: an analysis of patient
      discharge data.
AB  - OBJECTIVE: To investigate the functioning of a specialist out-patient
      Psychodynamic Psychotherapy Service by studying demographic characteristics of
      patient referrals and referral sources. To investigate the effect of number of
      treatment sessions on outcome; and to discuss the results in the light of some
      prevailing stereotypes about psychotherapeutic treatment. DESIGN: Analysis of
      discharge data on a cohort of patients discharged from a psychotherapy clinic.
      SETTING: An out-patient psychotherapy clinic serving the West Sector of the City
      of Glasgow. SUBJECTS: All patients discharged between mid 1993 and 1998. RESULTS:
      The clinic served all General Practices within eight postal code areas in West
      Glasgow (catchment population 260,000). Over a five year period 1648 patients
      were discharged from the clinic; 68% of referrals were from General
      Practitioners, 18% from Psychiatrists and the remainder from Clinical
      Psychologists, Consultant Physicians and Surgeons. A wide range of diagnostic
      conditions were encountered with personality disorder being diagnosed in more
      than one-third of patients seen. Successful outcome, assessed by patients'
      subjective ratings on a four point scale at termination of treatment, showed a
      50% improvement rate achieved between 7-12 treatment sessions in the Non
      Personality Disorder group, and between 12-20 treatment sessions in the
      Personality Disorder group. In total the proportion of not improved and improved
      ratings was 61% and 39% respectively. Four hundred (73%) of the not improved
      group received, five sessions or less. CONCLUSIONS: The results indicated that
      the Psychotherapy Service treated a large number of patients, many from middle to
      high areas of deprivation, and that improvement could be effected over relatively
      short time periods. The data did not conform to existing stereotypes such as
      psychotherapy being confined to the treatment of "worried well", affluent groups.
      It took twice as many sessions to achieve a 50% improvement rate in patients with
      a diagnosis of personality disorder compared with patients without such a
      diagnosis.

PMID- 12813823
TI  - The use of sign language interpreting services by medical staff in Dundee.
AB  - OBJECTIVE: To investigate awareness and use of the Sign Language Interpreting
      (SLI) service among doctors in Dundee and to look at reasons for use and non-use
      of this service. DESIGN: A Questionnaire study. SETTING: Dundee. SUBJECTS: All
      General Practitioners and Hospital Consultants working in Dundee. RESULTS: Sixty
      seven percent of General Practitioners and 55% of Consultants returned completed
      questionnaires. Only 38% and 60% respectively of these two groups were aware of
      the Sign Language Interpreting Service. Most doctors felt that using the SLI
      would reduce consultation time but only 18% and 24% have arranged this.
      CONCLUSION: Previous reports into SLI services have looked at client need,
      service provision and use. This study has highlighted the lack of awareness that
      still exists with regard to the needs of the Deaf community during medical
      consultations. This has to be addressed not least in light of the disability
      discrimination act 1995.

PMID- 12813824
TI  - Professional composition of community learning disability teams in Scotland:
      implications for service provision.
AB  - A survey of all trusts in Scotland who provided specialist services to people
      with learning disabilities was made with a response rate of 100%. An examination
      was made of the professional composition of the community learning disability
      teams and the population covered. A disparity was found across Scottish trusts in
      the professions represented in the community learning disability teams with some
      professions having no input. Nursing and Clinical Psychology were found to be the
      two professional groups with largest representation across Scotland and along
      with Speech and Language Therapy had representation in all of the Teams. A review
      of some of the factors which have impacted on the role and professional
      composition of these services is made and the implications discussed.

PMID- 12813825
TI  - Ageism helps to ration medical treatment.
AB  - The world's population is ageing and this will have inevitable consequences for
      the demands on acute and longer term health care resources. Old age is rarely
      characterised by positive images and older age stereotypes are often unflattering
      and ugly. Many older people experience social exclusion as a result of low
      income, poor housing, little family support, isolation, disability and illness.
      Ageism is a prejudice which is invoked to deny older people the things they seek
      and ageism in medicine probably reflects ageism in society as a whole. Old age is
      a criterion for rationing health care resources and it occurs at all levels in
      the National Health Service. Older subjects are often excluded from research
      trials, have their surgical operations cancelled too often and are less often
      accepted for cardiological investigation and intervention. Women over 65 are not
      routinely invited for breast cancer screening and, once they are diagnosed, they
      may not be offered the same treatment as younger women. Ageism in clinical
      practice should be combated by better education of healthcare workers and
      treatment decisions should only be taken on an individual basis and not on
      stereotypical views. 'Age, I do abhor thee, Youth, I do adore thee.' Shakespeare,
      The Passionate Pilgrim.

PMID- 12813826
TI  - High service users: does the clinical psychologist have a role?
AB  - OBJECTIVE: To assess the impact of psychological intervention on high users of
      the GP service. DESIGN: A sample of high-attenders was offered the opportunity to
      attend an interview with a clinical psychologist. A three-year (one year before
      and two years after psychological intervention) survey of patient records was
      carried out to determine the pattern of patient attendances. In addition, GP and
      patient satisfaction questionnaires were utilised to rate the psychological
      service. SETTING: A GP surgery situated in the coastal region of Scotland.
      SUBJECTS: All adult patients, who had consulted over 12 times in the 12 months
      prior to the beginning of the study except those who had ongoing medical problems
      that the GP felt were being dealt with adequately, were invited to a
      psychological interview. In all, 174 invitations were sent, and 101 agreed to
      psychological intervention. RESULTS: After three months both the GPs and patients
      positively rated the input of the psychologist. There were short-term benefits
      from the psychological intervention in terms of attendance rates, which were not
      in evidence in the long term. For the participating group there was a significant
      decrease in attendance rate three months after psychological intervention
      compared to the non-participating group (P < 0.001). However, at 12 and 24 months
      after intervention both groups reduced attendance at a similar rate. CONCLUSION:
      Psychologist intervention had a short, but not long term, benefit, in reducing
      attendance rates. However, both GPs and patients found the provision of a report
      from the psychologist useful.

PMID- 12813827
TI  - Audit of emergency medical admissions during the winter 1997/1998.
AB  - OBJECTIVES: To test the hypothesis that a significant cause of rising medical
      admissions over the Christmas and New Year period is the failure of social and
      medical systems which support patients at home for most of the year; and to
      understand the reasons for admission during the winter months of an at risk
      population and to identify possible avoidable admissions. DESIGN: Structured
      interviews were conducted with patients within 48 hours of admission to collect
      information on home circumstances and contact with social, medical and primary
      care in the year prior to admission. In cases where the patient was unable to
      provide this information, case notes and nursing notes were reviewed. Discharge
      diagnosis was recorded at the end of the study period. SUBJECTS: Five hundred and
      thirty nine patients defined as an "at risk group" who were admitted to hospital
      as emergency medical admissions between 1st December 1997 and 31st January 1998.
      RESULTS: Subjects were predominantly female (58%). The major diagnostic groups
      were cardiac (27%) and respiratory (22%). Respondents indicated no change in
      primary care in the period preceding their admission, with the exception of day
      centre support. Sixty seven percent of patients fully interviewed received help
      from carers, friends or relatives with daily tasks and only seven (3%) reported
      receiving less input prior to admission. Forty five percent of these patients had
      seen a GP within the month prior to their admission. CONCLUSIONS: The study
      results showed no breakdown in either social or family support. In the group
      interviewed, the proportion who had experienced any decrease in social support
      during the period prior to admission was very small.

PMID- 12813828
TI  - Expanded emergency medical services for the provision of primary care in remote
      rural areas.
AB  - It is now widely recognised that a potential recruitment crisis is looming in the
      provision of primary care physicians for remote rural areas of the United
      Kingdom. Anecdotal evidence suggests that rural registrar, associate and
      principal vacancies are becoming increasingly difficult to fill and for many
      rural GPs locums are an impossible dream. Many practitioners are no longer
      prepared to work in areas where out-of-hours cooperatives are not available. We
      are now faced with the very real possibility that in some remote areas of the
      Scottish Highlands and Islands the recruitment of suitable GPs may no longer be
      possible. So what are the alternatives? In October 1999 I visited a community in
      the mountains of northern New Mexico which has had to deal with this very
      problem.

PMID- 12813829
TI  - Consent--who, what, where, when?
AB  - OBJECTIVE: An investigation of current practise for obtaining and documenting
      informed consent in Scottish Ear, Nose and Throat (ENT) departments. DESIGN: A
      telephone survey of junior representatives of each ENT department. Each junior
      was asked a series of questions regarding who discussed the operations with
      patients who signed the consent forms and whether any form of training was given.
      SETTING: May 1999. RESULTS: In 80% of cases the responsibility for taking written
      consent fell to the most junior members of staff. Consultants have a pre
      operative discussion, with their patients most of the time but only rarely is
      this discussion documented. Training in the process of consent is given in only
      one of 15 departments. CONCLUSION: Despite increasing negligence claims and clear
      guidelines from the General Medical Council the responsibility for obtaining
      written consent from pre-operative patients still rests with the most junior
      medical staff of the ENT departments of Scotland. We suggest that this situation
      is neither prudent nor fair and have put forward two simple proposals to rectify
      the situation.

PMID- 12813830
TI  - The assessment of a "nurse led" deliberate selfharm service.
AB  - OBJECTIVE: To determine the effectiveness of a nurse led deliberate selfharm
      assessment service. DESIGN: Nine month retrospective survey and comparison with
      previous system. SETTING: Stobhill General Hospital, North Glasgow. SUBJECTS: Two
      hundred and eighty three Medical inpatients referred following deliberate
      selfharm, with completed data on 272 cases. RESULTS: The service significantly
      reduced admissions to psychiatric inpatient care from 24% to 7%. A dedicated
      nurse led service, has led to consistency in parasuicide assessments, reduced
      stigma and negativity towards DSH patients, led to better joint working between
      Stobhill General Hospital and Psychiatric services and reduced inappropriate
      psychiatric outpatient referrals. CONCLUSIONS: A dedicated nurse led DSH
      assessment service benefits patients and reduces psychiatric hospital admissions.
      A member of the psychiatric staff working on a daily basis within the general
      medical wards enhances joint working, ensures smoother communication between
      helping agencies and increases treatment options.

PMID- 12813831
TI  - Managing child and adolescent mental health problems: the views of general
      practitioners.
AB  - OBJECTIVE: To investigate issues influencing the role of general practitioners in
      managing child and adolescent mental health problems. DESIGN: A postal
      questionnaire survey inviting respondents to rate statements about managing child
      and adolescent mental health issues. SETTING: Population of urban Scottish
      general practitioners. SUBJECTS: General practitioner principals. RESULTS: Of the
      56% who responded, 31.3% reported that child and adolescent mental health
      services (CAMHS) were easy to access. Only a minority agreed that users' concerns
      prevented them from referring to CAMHS, and that these were more likely with
      young people or parents than with children. The number of respondents who
      considered their knowledge base, experience or training in this area to be
      adequate was particularly low. CONCLUSION: There may be a significant mismatch
      between what is expected of general practitioners in relation to child and
      adolescent mental health problems and what general practitioners themselves feel
      they are equipped to deliver.

PMID- 12813832
TI  - Recruitment to multicentre trials: the impact of external influences.
AB  - A multicentre randomised controlled trial needs to recruit sufficiently large
      numbers of centres, clinicians and patients Delays in reaching recruitment
      targets are common and often necessitate extended recruitment periods with
      associated increased costs. The Scottish Back Trial and the MRC Laparoscopic
      Hernia Trial are used to illustrate how national clinical, economic and political
      factors can impact on the conduct of a multicentre trial. Changes in clinical
      practice, restructuring of the NHS and research and development funding, and
      changes in the procedures for obtaining local research ethics committee approval
      had adverse effects on recruitment. In addition, the extent to which changes in
      patient knowledge and attitudes to clinical trials could influence recruitment
      should not be ignored. In response to these obstacles both trials extended the
      recruitment period, identified additional recruitment centres and reduced the
      overall sample size. External factors which could compromise the successful
      completion of a d trial need to be recognised and addressed at an early stage.

PMID- 12813834
TI  - The review of the public health function in Scotland: implications for the
      National Health Service.

PMID- 12813835
TI  - Organisation of services for acute stroke in Scotland--report of the Scottish
      stroke services audit.
AB  - An audit was undertaken of hospital service provision for acute strokes in
      Scotland, using as a template key recommendations in the four SIGN guidelines on
      management of stroke. A questionnaire and structured interview was undertaken of
      key personnel in the 43 Trusts and three directly managed units providing in
      patient stroke care in Scotland, and the 15 Health Boards commissioning stroke
      care. All Trusts and Health Boards participated and a complete set of information
      for each was recorded on a data-base and analysed. This report gives an overview
      for 14 key components of an integrated stroke service with results presented in
      four bands according to Trust type determined by the number of strokes admitted.
      No Trust provided all key components and for a few components a lack of provision
      was widespread, e.g. fast-track assessment clinics for TIA and minor stroke,
      access to CT scanning within 48 hours. Variation occurred between Trusts of
      similar size, between Trusts of different sizes. Overall the Health Boards were
      at a preliminary stage in the development of stroke specific service
      specifications. The results of the audit are a view of stroke services around
      April 1998, and should enable commissioners and providers to consider how to
      progress implementation of the clinical guidelines on stroke care.

PMID- 12813836
TI  - Anti-psychotic drug prescribing trends in primary care in Scotland 1994-97.
AB  - OBJECTIVE: To describe trends in the use of anti-psychotic drugs prescribed in
      Primary Care in Scotland. DESIGN: Information on prescription numbers and costs
      were obtained from the Pharmacy Prescribing Division. SETTING: Scotland 1994
      1997. Results Prescriptions for anti-psychotic drugs in Primary Care in Scotland
      increased by 28% in the period April 1994-December 97. In the same period,
      quarterly costs increased from 523,971 Pounds to 1,339,215 Pounds, an increase of
      155%. Ninety per cent of the increase is accounted for by use of the five drugs
      risperidone, sertindole, olanzapine, clozapine and quetiapine. Health Board areas
      vary markedly in their uptake of the new drugs. CONCLUSION: The use of new anti
      psychotic drugs in Scotland represents a substantial additional investment in
      mental health care. This has happened with little discussion or debate. Scotland
      needs to make explicit decisions on the place of newer anti-psychotics in
      treatment, and on the balance between investing in these drugs and investing in
      other aspects of mental health services.

PMID- 12813837
TI  - Tuberculosis in children at the Royal Hospital for Sick Children, Glasgow.
      January 1995-April 1998.
AB  - BACKGROUND: The management of paediatric tuberculosis can be complicated. Since
      1995, children referred to the Royal Hospital for Sick Children have been managed
      at a specialist tuberculosis clinic, in an attempt to standardise diagnosis,
      treatment and follow-up. AIMS: To review the management of paediatric
      tuberculosis at the Royal Hospital for Sick Children, Glasgow, from January 1995
      to April 1998. METHODS: Retrospective study using information from the management
      database of all children treated for tuberculosis since January 1995. RESULTS:
      Seventy two children have been treated (median age 5.9 [range 2.2-9.2] years; sex
      male:female 40:32; 76% Caucasians): 43 for tuberculosis disease, 21 for
      tuberculosis infection (chemoprophylaxis) and eight as tuberculosis contacts.
      Sixty three per cent were identified by contact tracing eighty one per cent of
      Mantoux tests were documented accurately. Of those with disease, 93% had gastric
      washings taken, and positive microbiological confirmation was obtained in 33%.
      All patients with disease were commenced on the chemotherapy regimen recommended
      by the British Thoracic Society. 88% completed treatment. Eighty four per cent of
      those with disease had been notified. Treatment of those in the infection or
      contact groups were treated more aggressively than the British Thoracic Society
      guidelines, with six months of treatment with isoniazid and rifampicin. Directly
      observed therapy was used in 17 children (24%). Only 53% of Indo-asian children
      had received BCG immunisation. CONCLUSIONS: Most children were managed according
      to the British Thoracic Society guidelines. A management system, with a
      computerised database, has facilitated both patient management and audit, and
      ensured the delivery of quality care.

PMID- 12813838
TI  - Pathways to psychiatric admission: a study of 100 consecutive admissions to south
      Glasgow acute adult psychiatric wards.
AB  - OBJECTIVE: To examine routes of admission to psychiatric beds and to identify
      factors that influence this. DESIGN: Retrospective casenote study. SETTINGS:
      Acute adult psychiatric wards in South Glasgow. SUBJECTS: One hundred consecutive
      admissions over a one month period. RESULTS: There were twelve discrete sources
      of referral. Psychiatrists and Community Psychiatric Nurses (CPNs) together
      accounted for 32% of referrals and General Practitioners for 25%.
      Schizophreniform and mood disorders affected 34% and 31% of the patients
      respectively whilst 25% of those admitted were deemed to have no major mental
      illness. Twenty-seven percent of patients were admitted to an inappropriate ward
      because the appropriate ward was full: personality disorders and drug problems
      were statistically significantly over represented amongst these "boarders". Over
      80% of patients were admitted by the on-call psychiatric SHO rather than by a
      doctor from their own team. Only 32% of admissions occurred during office hours.
      Psychiatrists and CPNs were significantly less reliant upon emergency admission
      procedures than were other referrers. The pathway to admission was independent of
      patient's sex, diagnosis, legal status, previous contact with services and of
      ward location. Community-based psychiatrists and CPNs admitted relatively fewer
      patients with schizophrenia than did their hospital-based colleagues. CONCLUSION:
      Patients are referred for admission to acute psychiatric wards from a variety of
      sources. Most admissions occur outwith office hours. In a large majority of cases
      the admitting psychiatrist is the on-call SHO, rather than a doctor from the team
      responsible for the patient's management. Our data suggest that this is not a
      reflection of the type of cases referred for urgent assessment but rather a
      failure of certain aspects of service provision.

PMID- 12813839
TI  - National audit of the management of injured patients in 20 Scottish hospitals.
AB  - The Scottish Trauma Audit Group was established in 1991 to observe and improve
      the management of seriously injured patients in four Scottish teaching hospitals.
      There are currently 25 hospitals contributing to the national database. This
      prospective audit monitors the management of approximately 98% of seriously
      injured patients in Scotland. This report presents an analysis of the management
      of 23479 patients who were admitted to hospital for at least three days or who
      died in hospital as a result of their injuries. The audit has specifically
      addressed the concerns raised by the working party of the Royal College of
      Surgeons in 1988 and the National Audit Office in 1992. National standards were
      agreed and implemented by STAG in 1997. STAG has demonstrated that 73.5% of
      seriously injured patients presented outwith 'normal' working hours when staffing
      and support services are at their lowest level. Seniority of accident and
      emergency doctor was associated with improved outcome in injured patients. An
      increase in the presence of consultants in accident and emergency medicine,
      anaesthetics and surgery has been demonstrated and a reduction in the mortality
      of seriously injured patients is evident. There was no evidence of a trimodal
      distribution of death as a result of injury. There has been a significant
      increase in the survival of seriously injured patients over the last six years
      from 65.3% to 75.6%. In terms of survival, the management of injured patients in
      Scotland is significantly better than that of the rest of the UK.

PMID- 12813840
TI  - Promoting breast screening in Glasgow.
AB  - OBJECTIVE: To establish whether there is a role for advertising in the promotion
      of the Breast Screening Programme and what the role of advertising might be.
      DESIGN: Four hundred and sixty questionnaires were completed by women attending
      their breast screening appointment. Quantitative and qualitative data were
      collected from the static unit at Calder Street and the mobile unit in Govan.
      SETTING: The advertising (budget 30,000 Pounds) campaign ran over an eight week
      period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used
      included press advertising, The Glasgow Underground, adshells, bus advertising
      (interiors) and poster distribution via local outlets. RESULTS: Forty-two per
      cent of the sample were aware of the campaign. Ninety-seven per cent liked the
      campaign images. Eighty eight per cent felt that breast screening should be
      advertised more. Screening uptake increased in the areas covered by the
      advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) 
      59%-61%. CONCLUSION: Women were very supportive of the role of advertising for
      the Breast Screening Programme. In particular they found the campaign images and
      messages reassuring, supportive and credible. Their views suggest that the role
      of advertising should be: To raise awareness of the service To make women more
      conscious of the benefits of screening To change public perceptions of the
      screening process However, it is recognised that a fully integrated approach is
      required for the promotion of the service to account for the improvement in
      uptake, as advertising cannot be expected to work in isolation.

PMID- 12813841
TI  - An audit of NHS Trust alcohol policy referrals to an occupational health service.
AB  - An exploratory review of 33 referrals to an Occupational Health Service of
      employees with alcohol problems provided information on age and sex, job
      category, mode of referral, medical and social problems and outcome. Case records
      were examined providing information on clinical assessment and the treatment
      options. The high rates of relapse, drop-out and refusal of help, supported the
      view that this population had serious alcohol problems. Clinical recording by
      occupational physicians showed a marked variability. No doctors were included in
      the sample although this group is known to be vulnerable. Blood testing was used
      infrequently. Occupational health clinical practice could be enhanced by the use
      of clinical protocols, systems of morbidity recording and co-operative studies
      with other agencies. Further prospective studies are needed.

PMID- 12813842
TI  - Screening sigmoidoscopy: a randomised trial of invitation style.
AB  - OBJECTIVES: To examine uptake rates for screening sigmoidoscopy and whether
      offering prior consultation about sigmoidoscopic screening improves the uptake
      rate. DESIGN: Patients between 50.5-60.5 years of age registered with one
      practice were identified and offered screening sigmoidoscopy. Patients were
      randomly allocated to one of two groups. The first group was sent an invitation
      to have screening sigmoidoscopy along with an explanatory leaflet. The second
      group was sent the same invitation and leaflet but with an added option to
      discuss the test in the first instance with their general practitioner. Response
      rates (regarding reply to initial invitation and subsequent attendance for
      screening) in the two groups were measured. SETTING: Urban General Practice,
      Dundee, Scotland, UK. RESULTS: The overall uptake rate was low at 24%.
      Significantly fewer people in the second group (i.e. those with the option to
      discuss first) replied to the initial invitation. Assessing those who did reply,
      there was no difference between the two groups in numbers who thereafter went on
      to attend for screening. Only two percent of people took up the offer to find out
      more about the test from their general practitioner. CONCLUSIONS: The offer of
      flexible sigmoidoscopy as a screening test for colorectal cancer generates little
      interest in this population at present and compliance rates are low. The offer of
      prior consultation about the procedure with a patient's own general practitioner
      is not sufficient to generate interest. These results highlight potential
      difficulties with the introduction of a mass screening program.

PMID- 12813843
TI  - Which women want food during labour?: results of an audit in a Scottish DGH.
AB  - OBJECTIVE: To assess the proportion of women who would want to eat during labour
      and to identify any distinguishing characteristics of this group. DESIGN: Audit
      questionnaire, completed within 36 hours of delivery. SUBJECTS: One hundred and
      forty nine post-natal women, over a five-week period. RESULTS: A significant
      minority (30%) of women would wish to eat during labour. A quarter of these feel
      that eating would have significantly enhanced their satisfaction during the
      event. In addition, some of these women admitted to eating secretly during
      labour. CONCLUSIONS: Clinicians involved in the care of pregnant women should be
      aware of the arguments for and against allowing food during labour, in order to
      help these women reach an informed decision.

PMID- 12813844
TI  - Public involvement.

PMID- 12813845
TI  - Presenting features of paediatric meningococcal disease--a five year experience
      from a paediatric accident and emergency department.
AB  - OBJECTIVES: To determine the clinical features, initial management and outcome of
      meningococcal disease presenting to a paediatric accident and emergency (A&E)
      department. DESIGN: A retrospective study of all cases of meningococcal disease
      seen in the department over a five year period. SETTING: A paediatric A&E
      department which treats approximately 30,000 patients a year. SUBJECTS: All
      children under the age of 13 years with a discharge diagnosis of meningococcal
      disease RESULTS: Fifty patients, forty-six with microbiological confirmation of
      their diagnosis were identified. Sixty six percent of patients were seen first by
      their general practitioner. However only 28% had received prehospital parenteral
      antibiotics. Twenty six percent of children had neither meningism nor a classical
      purpuric rash, 60% showed signs of shock and 66% had an altered conscious level.
      The case fatality rate was 4%, with 78% making a full recovery. CONCLUSION:
      Classical features of meningococcal disease are often absent. Assessing simple
      clinical parameters such as capillary refill, respiratory rate and conscious
      level adds to the detection of the disease. If meningococcal disease is suspected
      parental benzylpenicillin should be given and the child transferred to hospital.

PMID- 12813846
TI  - Promoting public confidence in the NHS: the role of the Clinical Standards Board
      for Scotland.

PMID- 12813847
TI  - Breastfeeding in Scotland--statistical sources.
AB  - INTRODUCTION: The health benefits of breastfeeding for babies and mothers are
      increasingly recognised. In Scotland, a national breastfeeding target has been
      set and national policies commend the promotion and support of breastfeeding. In
      order to set realistic local breastfeeding targets, and to evaluate success in
      increasing the initiation and duration of breastfeeding, Health Boards need
      accurate local data on breastfeeding rates. OBJECTIVE: To examine existing
      Scottish sources of routinely collected data on infant feeding intention and
      practice, and to make recommendations for the future collection, dissemination
      and quality of such data. METHODS: Information on Scottish infant feeding data
      was collected from published sources and from personnel responsible for infant
      feeding data within larger infant and child health data sets. Data for Glasgow
      were analysed for completeness. RESULTS: Four major sources of routinely
      collected data exist, one of which provides national figures only. The other
      three collect local data on feeding intention and practice at a variety of stages
      from pregnancy to baby's age 8/9 months. Whilst some data are available locally,
      there is no routine dissemination of data at all stages throughout Scotland. The
      quality and completeness of data require further investigation. CONCLUSIONS:
      Attention should be given to developing the use of existing routinely collected
      sources of data to provide regular, reliable information on local breastfeeding
      rates to assist the monitoring and implementation of local breastfeeding
      strategies. A small group of health professionals, health information staff and
      researchers should be convened by ISD to pursue this task.

PMID- 12813848
TI  - Anticholinesterases in the treatment of Alzheimer's dementia--the first year's
      experience in Argyll & Clyde.
AB  - The local experience of the introduction of a new anticholinesterase treatment
      for Alzheimer's dementia is described, including the use of a protocol to
      introduce the use of these drugs. The results in the first 233 patients seen are
      reported. The protocol seemed to anticipate SMAC. guidelines and to be easy to
      operate; the drug appeared to have clear clinical effect.

PMID- 12813849
TI  - Evidence-based psychiatry--do psychiatrists want it and can they do it?
AB  - OBJECTIVE: To examine (a) psychiatrists' attitudes to evidence-based psychiatry,
      (b) whether psychiatrists have identifiable clinical information needs, (c) if
      such information is practically obtainable, and (d) how psychiatrists respond to
      the information obtained. DESIGN: We surveyed senior psychiatrists to enquire
      about their attitudes and to request up to three clinical questions they would
      like answered. We attempted to find evidence to answer the five most frequently
      asked questions using recommended strategies and timed how long it took us. We
      fed our answers back to those who had asked one of these questions and asked if
      they found the answers useful. SETTING: Specialist registrars, senior registrars
      and consultants in south-east Scotland. RESULTS: Ninety three (76%) of those
      surveyed returned usable questionnaires. Respondents thought that only 40% of
      their practice is evidence-based. They reported that 'insufficient time' was the
      biggest barrier to implementing evidence-based psychiatry. The most frequently
      asked questions concerned the treatment of major psychiatric disorders. It took
      us--three experienced researchers, trained in critical appraisal, with excellent
      local facilities--between 15-60 minutes to answer each question. Most of those
      who had asked the questions (15/22) thought they would not have been able to
      answer them and stated that such a 'question answering service' as piloted here
      would be valuable. CONCLUSIONS: An evidence-based psychiatry appears to be
      desirable and possible, but impractical for the individual clinician. There is a
      need for short accessible evidence-based summaries of optimal treatment in
      psychiatry.

PMID- 12813850
TI  - Adult pertussis in a general practice.
AB  - OBJECTIVE: To examine serologically the incidence of pertussis in a group of
      adults (> 15 years of age) presenting to their General Practitioner with symptoms
      which suggested the possibility of pertussis. DESIGN: One year's study of the
      results of testing blood samples. This was followed by a questionnaire to the
      General Practitioners involved, asking information on all the patients tested.
      SETTING: Specimens were tested as part of the normal workload in the Microbiology
      Department of a District General Hospital. SUBJECTS: The patients all attended a
      Health Centre in South Lanarkshire which caters for a population of 12,749
      people. RESULTS AND CONCLUSIONS: Twenty of fifty six patients tested (35.7%)
      produced serological evidence of recent pertussis infection. The average age of
      the positive patients was 43.5, and the duration of their symptoms, before
      testing, was 4.2 weeks. The results suggest that pertussis in adults is not
      uncommon. Symptoms of "whoop" and/or vomiting were seldom reported in this
      series. "Paroxysmal coughing", "nocturnal coughing", and "shortness of breath"
      were more common in the positive cases than in the negative ones. The use of
      antibiotics did not appear to have any beneficial effect, probably due to them
      being given too late after the onset of infection. Most adults are susceptible to
      pertussis, as vaccine-induced immunity declines and is absent after 12 years
      following vaccination. In a vaccinated population, adults are now the primary
      source of infection for susceptible infants.

PMID- 12813851
TI  - An audit of the implementation of guidelines to reduce wound infection following
      caesarean section.
AB  - OBJECTIVE: National guidelines suggest that antibiotic prophylaxis should be
      given at all emergency Caesarean sections and considered at elective procedures
      in an attempt to reduce wound infection rates. It is recommended that both
      infection rates and the administration of antibiotics should be audited. In the
      absence of a local protocol an audit was designed aiming to audit the infection
      rate against a gold standard of a wound infection rate less than 5%. METHODOLOGY:
      A retrospective case note review was performed for all Caesarean section
      occurring over a six month period. Guidelines were introduced to address
      deficiencies and the audit repeated a year later. RESULTS: The wound infection
      rate in the absence of local guidelines for antibiotic prophylaxis was 10%. The
      major factor related to infection was a failure to give antibiotics particularly
      at elective Caesarean section. Re-audit following the introduction of a protocol
      for the administration of antibiotics at all Caesarean sections found a
      compliance rate of over 97% with a reduction of the infection rate to around 3%.
      CONCLUSION: This study supports the use of audit in the implementation of
      guidelines based on published evidence and local results.

PMID- 12813852
TI  - Is this satisfaction survey satisfactory? Some points to consider in their
      planning and assessment.
AB  - Measuring patient satisfaction is one of the commonest evaluation activities in
      the NHS. The main aim of the article is to highlight some of the most important
      aspects of planning, undertaking and critically appraising satisfaction surveys.
      Key areas considered include: survey aims; definition of concerns; nature of
      survey populations; methods; interpretation of results; and outcomes and
      implementation.

PMID- 12813853
TI  - Drug action team strategies in Scotland.
AB  - OBJECTIVE: To compare the Strategic Plans of Scottish Drug Action Teams (DATs) to
      the recommendations of the Scottish Office Ministerial Task Force Report. DESIGN:
      Extraction of information from the strategic plans of DATs. SETTING: All 15
      Scottish DATs 1995-96. RESULTS: Five DATs did not include a membership list in
      their Strategy, and two stated the organisations represented, but not the
      identity of individual members. Where individuals were identified, Health Boards,
      Social Work departments, Education and Police were always members. The median
      number of members was 12 (range 4-16). Most areas had plans to improve
      information on drug misuse. Every plan mentioned preventive work with young
      people. In Criminal Justice settings, use of Children's Hearings (20% of plans),
      substitute prescribing linked to probation (13%) and prison aftercare schemes
      (33%) were mentioned less commonly. Substitute prescribing (87% of DATs), the
      role of General Practitioners (100%) and monitoring mechanisms (87%) were the
      service issues mentioned most often. Of other service issues in the Ministerial
      Report, those mentioned least by DATs were childcare linked to services (20%);
      services for people from ethnic minorities (33%); education on dangers of
      injecting to existing drug users (33%); women--only residential services (33%);
      services for women (46%) and role of pharmacists (53%). CONCLUSION: Membership
      was from a core of statutory agencies. Young people were the priority of most
      DATs. Criminal Justice arrangements and services for special groups of people
      were not well developed in many plans. DATs should review their focus on these
      groups.

PMID- 12813854
TI  - Uptake of the children's traffic club in Lothian.
AB  - OBJECTIVE: To calculate the uptake of the Children's Traffic Club in Scotland
      (CTCS) in Lothian and the road traffic casualty rate of children aged 0-14 living
      in areas with different deprivation categories. DESIGN: Analysis of road traffic
      accident hospital admissions, 'STATS 19' (road traffic accident police reports)
      and CTCS uptake data in affluent, 'intermediate' and disadvantaged households.
      SETTING: The Lothian Health Board area. RESULTS: Affluent households have both
      the highest CTCS uptake rates and the lowest rates of road traffic accidents. The
      most disadvantaged populations have hospital discharge rates over three times
      that of people living in more affluent parts of Lothian. CONCLUSIONS: Minor
      changes in how the CTCS is run and fostering a multiagency approach to childhood
      accident prevention could improve both CTCS uptake and effectiveness of road
      safety measures.

PMID- 12813856
TI  - "A survey of general practitioners (GPs) in north east Scotland on practice based
      counsellors services". Health Bulletin 1999; 57(3):175-179.

PMID- 12813857
TI  - "Higher specialist training--teething problems." Health Bulletin 57(4): 300-311.

PMID- 12813858
TI  - Diagnosis and treatment of coronary heart disease in women: systematic reviews of
      evidence on selected topics.

PMID- 12813859
TI  - Effect of endocrine disrupters on thymocytes in vitro.
AB  - In a previous paper we reported that endocrine disrupters (EDs) such as 4, 4'
      isopropylidene diphenol (Bisphenol A: BPA), bis(2-ethylhexyl) phthalate (EHP)
      stimulated proliferative responses and cytokine productions of murine spleen
      cells in vitro. In this paper we report our studies on the effect of EDs on
      murine thymocytes in vitro. EDs such as BPA, EHP and diethyl stilbesterol
      enhanced the proliferative responses of thymocytes. The proliferative responses
      of in vitro precultured thymocytes with EDs were markedly enhanced by the
      secondary stimulation with syngeneic spleen cells as antigen-presenting cells
      (syngeneic mixed lymphocyte reaction; MLR), when compared with thymocytes
      precultured without EDs. The responder cells were T cells, and they recognized
      the major histocompatibility complex (MHC) class II antigens on the antigen
      presenting cells. The precultured T cells with EDs were enhanced in the
      production of cytokines such as interleukin (IL)-3, IL-4 and interferon-gamma.
      These results suggest that EDs have a modulating activity on thymocyte functions.

PMID- 12813860
TI  - Estimating cadmium absorption rate in digestive organs calculated from
      information of studies on cadmium conducted in Japan.
AB  - The absorption rate of cadmium (Cd) in the digestive organs is reported to be 0.5
      8% in Friberg's textbook. This value was obtained from experimental studies. The
      object of the present study is to obtain the value from the Cd intake amount by
      ingestion, the Cd absorption amount by respiration and smoking, and the total Cd
      absorption amount calculated from the Cd accumulation amount in organs reported
      in articles including not only experimental but also epidemiologic studies
      conducted in Japan. The oral intake amounts of Cd in Japan were obtained from a
      published article to be 48 micrograms/day for males in the 1970s. The total Cd
      absorption amount that was calculated from the Cd accumulation amount in organs
      of 223 male subjects autopsied following sudden death was found to be 6.8
      micrograms/day for male adults in the 1970s. The Cd exposure before the 1970s
      reflected the Cd absorption amount calculated from the Cd accumulation amount in
      the 1970s. The Cd absorption amount by respiration and smoking for males in the
      1960s was 1.0 microgram/day, and the difference of 5.8 micrograms/day between the
      above two corresponds to the Cd absorption amount in digestive organs before the
      1970s. The rice intake amount for Japanese in 1955-1965 was reported to be about
      1.4 times as much as that in 1975. Therefore the Cd absorption rate in digestive
      organs was estimated to be about 10% from these values, assuming that most of the
      change in Cd intake from food is derived from the amount of rice eaten in Japan.
      This value is somewhat greater than the values published in the literature.

PMID- 12813861
TI  - Role of cyclooxygenase-2 in bone resorption.
AB  - Prostaglandins (PGs) are abundant in bone and are potent regulators of bone cell
      function. Osteoblasts produce PGs, and this production is highly regulated by
      local and systemic factors. Bone resorption is a highly regulated process
      involving interactions of osteoclastic precursors with osteoblasts or stromal
      cells. Many factors that stimulate PGs production also stimulate resorption in
      organ and marrow culture. Cyclooxygenase (COX) is the rate-limiting enzyme in the
      conversion of arachidonic acid to PGs. There are two forms of COX, COX-1 and COX
      2. COX-2 is an inducible primary-response or immediate early gene. COX-2
      expression is induced by many factors through the transcriptional pathway in
      osteoblasts. Stimulated production of PGs by osteoblasts requires both the
      induction of COX-2 expression and the availability of arachidonic acid substrate.
      PGs are complex, potent regulators of bone cell function in vivo. PGE2, which may
      be the most important local eicosanoid in skeletal regulation, can stimulate
      resorption. We report that COX-2 expression and associated PG production are
      necessary for maximal resorption responses to 1,25 (OH)2D3 and parathyroid
      hormone (PTH). PGs can increase osteoclast formation by enhancing induction of
      the receptor activator of nuclear factor-kappa B ligand (RANKL) expression in
      osteoblasts and enhancing the action of RANKL on osteoclast precursors by
      inhibiting granulocyte macropharge-colony stimulating factor (GM-CSF). In vitro,
      PGE2 can stimulate the differentiation of both osteoblasts and osteoclasts, and
      the net balance of these two effects under physiologic or pathologic conditions
      in vivo is not yet clear. Our in vivo data suggest that a role for COX-2 in bone
      resorption may be most evident when bone resorption is accelerated. Some of the
      complexity of PG actions on bone can be explained by the multiplicity of
      receptors for PGs. There are at least four distinct receptors for PGE2 with
      differential signaling pathways that have not yet been fully elucidated. Further
      studies are needed to clarify the specific pathways of PGs action in bone. Once
      this is accomplished, it may be possible to identify therapeutic applications of
      manipulating PGs in skeletal disorders.

PMID- 12813862
TI  - [The effect of formaldehyde exposure on cytokine production in murine alveolar
      macrophages].
AB  - The vapor of formaldehyde has been reported to represent a potential health
      hazard, resulting in respiratory dysfunction. To determine the potential role of
      alterations in the alveolar macrophages induced by inhalation of formaldehyde, we
      studied the cytokine production of murine alveolar macrophages. Mice were exposed
      at 0, 2.5, 5, 10 ppm of formaldehyde for 16 hrs daily, respectively. Durations of
      inhalation were 7, 14, 21 and 28 days. Immediately after the formaldehyde
      exposure, murine alveolar macrophages were harvested from the mice. 18 hrs after
      LPS stimulation, the cytokines (IL-4, IL-10, IFN-gamma, TNF-alpha) were measured
      in the supernatant of cultured murine alveolar macrophages using the ELISA
      method. No levels of formaldehyde exposure changed these cytokine productions.
      Either our dose or duration of formaldehyde exposure might not have been enough
      to produce significant changes of cytokine production of murine alveolar
      macrophages. Further experiments with low but longer formaldehyde exposure may be
      needed to understand the effect of formaldehyde on cytokine production.

PMID- 12813863
TI  - [Vertigo and dizziness associated with cerebral hemispheric lesions].
AB  - To investigate the clinical significance of vertigo and dizziness in diagnosing
      cerebral cortical lesion, we analyzed 12 patients with supratentorial lesions
      whose chief complaint was rotational vertigo or non-rotational dizziness. There
      were 8 patients with right, and 4 with left hemispheric lesions. The lesion was
      localized in the vicinity of the central sulcus in 3 patients, temporal and/or
      parietal regions in 6, and occipital region in 3. Vertigo was seen in three
      patients, two of them with lesions in the vicinity of the central sulcus, and one
      in the temporo-parietal junction. The other 9 patients complained dizziness.
      Supratentorial lesions accompanied by dizziness or vertigo were mostly localized
      in temporal or central areas that were probably analogous to the vestibular
      cortex proposed by animal studies. Dizziness caused by occipital lesion might be
      due to imbalance of the neuronal network between the vestibular cortex and
      occipital lobe.

PMID- 12813864
TI  - [Development of a hospital information system simulator for education].
AB  - When teaching students the hospital information system, it is impossible to use
      an actual hospital information system because of security reasons. To overcome
      this problem, a simulator of the hospital information system for student
      education has been developed. The purpose of this system is to help students
      understanding a hospital information system from actual experience. The
      characteristics of this system are as follows: 1) Students can easily learn a
      hospital information system on the Web pages in the computer training room. 2)
      The present system is not as complete as a hospital information system, however,
      helpful explanations regarding the data processing have been inserted. 3) The
      fictional patient data have been prepared for the pages relating to the
      electronic medical chart. Consequently, students can understand what kind of data
      has been saved in this system. Through a questionnaire, students evaluated this
      system in terms of understandability. The result from four years between 1999 and
      2002 showed that 70% of them evaluated it as good system. We therefore consider
      this system to be effective over a short period of time, and useful for medical
      education.

PMID- 12813865
TI  - [Formaldehyde exposure and multiple chemical sensitivity].
AB  - Multiple chemical sensitivity (MCS) is characterized by various somatic symptoms
      which cannot be explained organically and by sensitivity to extremely low
      concentrations of chemicals including formaldehyde. In the absence of a widely
      accepted definition of MCS, contradictory etiological hypotheses and therapeutic
      suggestions are discussed. Formaldehyde is a flammable, colorless and readily
      polymerized gas at ambient temperature. It is present in the environment as a
      result of natural processes and from man-made sources, including motor vehicle
      exhaust, residues, emissions, or wastes produced during the manufacture of
      formaldehyde, and cigarette smoke. Formaldehyde exposure is considered to be one
      of the causes of MCS. This review describes the current knowledge about MCS and
      preventive measures of the administration.

PMID- 12813866
TI  - [Interleukin 1 signal transduction].
AB  - In the human body, several factors play immunological roles. The molecular
      mechanisms of functions of these factors have been investigated extensively in
      the past. Interleukin 1 (IL-1) is a secreted protein and performs a central part
      in inflammatory responses. IL-1 binds to cell surface specific receptors and
      activates transcription factors through cytoplasmic mediators such as Myeloid
      differentiation factor 88 (MyD88), IL-1 receptor-associated kinase (IRAK) and TNF
      receptor-associated factor 6 (TRAF6). These are responsible for the induction of
      target genes, which are able to orchestrate or suppress the immune response. This
      review summarizes the available information to date on the signal transduction of
      IL-1.

PMID- 12813867
TI  - [Three cases of chronic volar dislocation of the distal radioulnar joint that
      were treated with the Sauve-Kapandji procedure].
AB  - Three cases of chronic volar dislocation of the distal radioulnar joint were
      treated with the Sauve-Kapandji procedure. All patients were in their twenties.
      They visited our clinic complaining limitation of forearm wrist rotation and pain
      around the wrist for more than 6 weeks after an injury. Radiograph and CT scan
      revealed chronic volar dislocation of the distal radioulnar joint. Closed
      reduction failed. The Sauve-Kapandji procedure was required to prevent the distal
      radioulnar joint from becoming unstable after open reduction. Range of motion of
      the injured wrist improved greatly, pain disappeared and they were able to return
      to sports after the operation and rehabilitation. Therefore, the Sauve-Kapandji
      procedure is effective in curing chronic volar dislocation of the distal
      radioulnar joint.

PMID- 12813868
TI  - The "geriatric" family history. Emotions and geography 'best' genes in late life.

PMID- 12813869
TI  - Diabetic polyneuropathy. Risk factors, patterns of presentation, diagnosis, and
      treatment.
AB  - Diabetic symmetrical distal neuropathy or diabetic polyneuropathy is the most
      common form of diabetic neuropathy and a leading cause of neuropathy in the
      United States. Complications include pain, loss of ambulation, and risk for
      amputation. Recognizing the typical pattern of presentation and risk factors for
      diabetic polyneuropathy is essential for making the correct diagnosis and
      determining appropriate workup and need for neurologic consultation. Intensive
      glucose control is the only therapy proven to prevent or slow the progression of
      diabetic polyneuropathy. Supportive therapies, including pain management and
      podiatric care, can improve quality of life and prevent chronic ulcerations.

PMID- 12813870
TI  - The new staging system for heart failure. What every primary care physician
      should know.
AB  - The primary care physician is in a unique position to have a major impact on the
      prevention of heart failure. Using the new system of classifying heart failure,
      the primary care physician can better evaluate and treat patients in the primary
      care setting. The new American College of Cardiology/American Heart Association
      staging system for heart failure emphasizes the structural condition of the heart
      as well as the prevention, evolution, and progression of heart failure. It is
      meant to complement the NYHA classification system, which has been used to
      describe functional limitations, not structural abnormalities.

PMID- 12813871
TI  - Older patients, Columbia shuttle.

PMID- 12813872
TI  - Rash associated with cold objects. Erythematous, edematous plaque appears after
      local cold exposure.

PMID- 12813873
TI  - Cognitive screening in the primary care setting. The role of physicians at the
      first point of entry.
AB  - There are many reasons why it is important to conduct the cognitive assessment
      and arrive at a preliminary diagnosis within the primary care setting. In
      addition to starting the patient on anti-cholinesterase medications, the
      physician must discuss with the family (and often the patient) issues related to
      financial matters and self-care. Alzheimer's patients who live alone may be
      targets for financial and personal exploitation, and are at risk for self
      neglect. Community support or provision might be needed to assist with medication
      compliance, provide nutritional services by shopping for prepared foods or
      through Meals on Wheels, housekeeping to maintain cleanliness, adult day services
      to provide social and recreational activities, live-in companions, and assistance
      with other instrumental activities of daily living. Sometimes more structured or
      institutional living is necessary. Generally, the primary care practice is not
      set up to coordinate these additional services, as well as to provide ongoing
      care. We will discuss potential solutions to providing ongoing care in next
      month's column.

PMID- 12813874
TI  - Bioinformatics becomes respectable.

PMID- 12813875
TI  - Hatchability of chicken embryos following somite manipulation.

PMID- 12813876
TI  - PCR-generated truncated positive control for PCR screening of embryonic stem cell
      clones.

PMID- 12813877
TI  - Optimized vector for conditional gene targeting in mouse embryonic stem cells.

PMID- 12813878
TI  - Overcoming obstacles in DNA sequencing of expression plasmids for short
      interfering RNAs.

PMID- 12813879
TI  - Cost-effective method to synthesize fluorescently labeled DNA size standards
      using cloned AFLP fragments.

PMID- 12813880
TI  - Multiplex allele-specific PCR with optimized locked nucleic acid primers.

PMID- 12813881
TI  - Encapsulation of acetylcholinesterase in preformed liposomes.

PMID- 12813882
TI  - Strategy to screen long DNA inserts in Escherichia coli.

PMID- 12813883
TI  - Ratio of loading dye to PCR product affects sensitivity of single-stranded
      conformational polymorphism analysis.

PMID- 12813884
TI  - Miniaturized SNP detection: quasi-solid-phase RFLP analysis.

PMID- 12813885
TI  - Old botanical techniques for new microscopes.

PMID- 12813886
TI  - Time course of bioluminescent signal in orthotopic and heterotopic brain tumors
      in nude mice.
AB  - In vivo bioluminescence imaging is becoming increasingly popular.  Quantification
      of bioluminescence signals requires knowledge of the variability and
      reproducibility of this technique.  The objective of this study was to analyze
      the time course of luminescent signal emitted from firefly luciferase-expressing
      tumors in two locations, following luciferin injection and at different times
      after tumor cell implantation.  Knowledge of the kinetics of the bioluminescent
      signals is required for the reliable quantification and comparison of signal
      during longitudinal studies.  The kinetics of bioluminescence was evaluated in
      orthotopic and heterotopic brain tumors in mice using a human brain tumor cell
      line constitutively expressing luciferase.  Tumor cells were implanted in the
      brains and flanks of the animals, and whole-body images revealing tumor location
      were obtained.  Tumor burden was monitored over time by the quantitation of
      photon emission.  The magnitude of bioluminescence measured in vivo varied with
      time after the injection of luciferin, as well as with dose, which necessitated
      that the comparison of the quantitative results take into consideration the time
      after injection.  Heterotopic and orthotopic tumors exhibited significantly
      different time courses; however, time after implantation as characterized by
      kinetic studies performed on days 4 and 14 after cell implantation revealed no
      significant differences in orthotopic tumors.  Future quantitative longitudinal
      studies must take into account the differences in the kinetics of different
      models.

PMID- 12813887
TI  - Two-color image analysis discriminates between mineralized and unmineralized bone
      nodules in vitro.
AB  - Functional assays of progenitor cell capacity for colony formation in vitro
      typically depend on the investigator's expertise with quantification.  The
      ability to enumerate and analyze colony types with standardized criteria with no
      bias would be a useful tool for research and drug development.  We report the
      development of a two-color automated analysis system for colony-forming unit
      osteoblasts that is capable of reporting progenitor frequency and bone nodule
      number size, and type (mineralized or unmineralized).  Our image analysis system
      was validated using the rat calvaria cell model to measure in vitro bone nodule
      development.  With computer-aided image analysis, data on nodules can be rapidly
      generated with a minimum of user bias and fatigue.  This novel tool will
      distinguish mineralized and unmineralized bone nodules, facilitates
      quantification, enable large-scale experimental design, allow for long-term data
      storage and tracking, and lead to the identification of new parameters that
      impact bone development.

PMID- 12813888
TI  - Designing XML schemas for bioinformatics.
AB  - Data interchange bioinformatics databases will, in the future, most likely take
      place using extensible markup language (XML). The document structure will be
      described by an XML Schema rather than a document type definition (DTD). To
      ensure flexibility, the XML Schema must incorporate aspects of Object-Oriented
      Modeling. This impinges on the choice of the data model, which, in turn, is based
      on the organization of bioinformatics data by biologists. Thus, there is a need
      for the general bioinformatics community to be aware of the design issues
      relating to XML Schema. This paper, which is aimed at a general bioinformatics
      audience, uses examples to describe the differences between a DTD and an XML
      Schema and indicates how Unified Modeling Language diagrams may be used to
      incorporate Object-Oriented Modeling in the design of schema.

PMID- 12813889
TI  - Improved protocol for SAGE tag-to-gene allocation.
AB  - Serial analysis of gene expression (SAGE) is a powerful method for large-scale
      analysis of gene expression patterns. SAGE yields digital information on
      transcript abundance by the use of short sequence fragments (tags). Because SAGE
      does not require a priori knowledge of the expressed genes in the starting
      material, SAGE can be used for gene discovery. Unfortunately, correct tag-to-gene
      discovery. Unfortunately, correct tag-to-gene allocation after SAGE remains
      problematic when the short sequence of the tag corresponds to more than one gene
      in the reference database or when novel yet uncloned genes were detected. To
      overcome this problem, we developed an improved protocol for the proper
      identification of tag-corresponding genes. It relies on the isolation of 3'
      terminal cDNA restriction fragments by the use of paramagnetic streptavidin beads
      and the ligation of linkers before the amplification step. Our protocol benefits
      from additional information encoded in each SAGE tag: its location 3'-terminal to
      the last NlaIII restriction site in the cDNA. In contrast to previously described
      protocols, stringent PCR conditions can be applied because of the length of the
      specific primers, which are composed of linker- and tag-specific sequences.
      Additionally, we demonstrate that our protocol yields quantitative information
      that can be used for further expression analysis of specific SAGE tags.

PMID- 12813890
TI  - Bacterial IMPDH gene used for the selection of mammalian cell transfectants.
AB  - Stable cell transfection is used for the expression of exogenous genes or cDNAs
      in eukaryotic cells. Selection of these transfectants requires a dominant
      selectable marker. A variety of such markers has been identified and is currently
      in use. However, many of these are not suitable for all cell types or require
      unique conditions. Here we describe a simple and versatile dominant selectable
      marker that involves bacterial IMP dehydrogenase (IMPDH), an enzyme essential for
      the replication of mammalian and bacterial cells. Although IMPDH is
      evolutionarily conserved, the bacterial enzyme is orders of magnitude more
      resistant to the toxic effect of the drug mycophenolic acid, which is an IMPDH
      inhibitor. We have demonstrated that transfection of human, monkey or Chinese
      hamster cell lines with an expression vector containing bacterial IMPDH and
      mycophenolic acid treatment resulted in the selection of colonies with a
      strikingly increased resistance to mycophenolic acid toxicity. Analysis of cells
      derived from these colonies indicated that the acquisition of this resistance was
      associated with bacterial IMPDH protein expression. As a proof of principle, we
      showed that mammalian cell transfection with a bicistronic IMPDH/GFP expression
      vector and mycophenolic acid treatment can be used to successfully select
      transfectants that express the fluorescent protein. These results indicate that
      bacterial IMPDH is a practical dominant selectable marker that can be used for
      the selection of transfectants that express exogenous genes or cDNAs in mammalian
      cells.

PMID- 12813891
TI  - Selection of chloroplasts by laser microbeam microdissection for single
      chloroplast PCR.
AB  - Laser microbeam microdissection and laser pressure catapulting offer the
      possibility of separating cell compartments, thus allowing for contamination-free
      analysis. Using these methods, we were able to select single chloroplasts of
      Nicotiana tabacum. Starting from homogenized leaf material, chloroplasts were
      purified by differential centrifugation and applied directly onto a poly-ethylene
      naphthalate membrane that was mounted on a microscope slide. Single chloroplasts
      were dissected under microscopic control and catapulted into a PCR tube.
      Subsequent PCR of a spacer region between the trnT and trnF genes verified the
      successful amplification of DNA from a single chloroplast. The advantage of this
      method compared to the use of capillaries or optical tweezers is that one is able
      to prepare high numbers of samples in a short time.

PMID- 12813892
TI  - Specificity of alternative splice form detection using RT-PCR with a primer
      spanning the exon junction.
AB  - A recently described strategy for splice variant specific detection by RT-PCR is
      based on the use of a primer spanning the junction between exons of the
      alternative splice form. However, this reaction may generate false-positive
      results in the presence of excess principal transcript. In this report,
      transcript variant 3 of T cell immune regulator gene 1 was used as a model to
      demonstrate a new method to ensure PCR specificity. Our approach permits the
      determination of detection specificity considering the full-length transcript
      amount. Furthermore, we demonstrated that the addition of a few molecules of a
      specific template dramatically increases the specificity of the reaction and
      allows for the detection of the alternative form, even in the presence of large
      amounts of the principal transcript. Competitor DNA for the alternative splice
      form is suggested as the specific template to achieve the detection specificity.
      Thus, we describe a simple strategy to avoid nonspecific amplifications for RT
      PCR using a primer spanning the exon junction.

PMID- 12813893
TI  - Positive selection vectors for high-fidelity PCR cloning.
AB  - The power of PCR cloning of a target DNA fragment is limited by polymerase
      induced mutations. While high-fidelity PCR products can be achieved by reducing
      the number of PCR cycles, the cloning of the very small amount of DNA thus
      amplified should give only a few recombinant clones (carrying an insert), which
      would be very difficult to screen from thousands of background false-positive
      clones generated by all the currently available vectors, including the positive
      selection vectors. False-positive clones are mostly generated by the
      recircularization of linearized vectors that have lost some bases at their ends
      due to digestion with contaminating exonuclease activities present in restriction
      enzymes, ligases, polymerases, and other reagents. To overcome this problem, two
      positive selection vectors, pRGR1Ap and pREM5Tc, have been developed, based on
      the principles of reporter gene reconstruction and regulatory element modulation,
      respectively. A PCR primer carrying a vector-specific sequence at its 5' end is
      used in PCR. When the resultant PCR products are ligated to the specific vector,
      an antibiotic resistance gene is expressed, thus donating positive selection
      capability to the harboring cells in a specific selection medium. These vectors
      cloned PCR fragments generated from less than a femtomole quantity of Escherichia
      coli genomic DNA after only three cycles of PCR amplification, thus greatly
      reducing the number of recombinant clones containing polymerase-induced
      mutations.

PMID- 12813894
TI  - Room-temperature hybridization of target DNA with microarrays in concentrated
      solutions of guanidine thiocyanate.

PMID- 12813895
TI  - Strategy for the design of custom cDNA microarrays.
AB  - DNA microarrays are valuable but expensive tools for expression profiling of
      cells, tissues, and organs. The design of custom microarrays leads to cost
      reduction without necessarily compromising their biological value. Here we
      present a strategy for designing custom cDNA microarrays and constructed a
      microarray for mouse immunology research (ImmunoChip). The strategy used
      interrogates expressed sequence tag databases available in the public domain but
      overcomes many of the problems encountered. Immunologically relevant clusters
      were selected based on the expression of expressed sequence tags in relevant
      libraries. Selected clusters were organized in modules, and the best
      representative clones were identified. When tested, this microarray was found to
      have minimal clone identity errors or phage contamination and identified
      molecular signatures of lymphoid cell lines. Our proposed design of custom
      microarrays avoids probe redundancy, allows the organization of the chip to
      optimize chip production, and reduces microarray production costs. The strategy
      described is also useful for the design of oligonucleotide microarrays.

PMID- 12813896
TI  - Microarray-based method for combinatorial library sequence mapping and
      characterization.
AB  - Here we describe a DNA-chip-based method for high-throughput sequence mapping.
      This involves competitive hybridization between short and differentially labeled
      fluorescent oligonucleotide probes and glass-supported PCR products. Competition
      between an excess of oligonucleotide probes targeting the same sequence segment
      improves sequence discrimination and reduces sensitivity to experimental
      conditions such as probe concentrations, hybridization, and washing temperatures
      and durations. The method was found to be particularly adapted to sequence
      mapping of combinatorial libraries obtained by DNA shuffling between members of a
      gene family. We present an application of this technique for the characterization
      of recombination biases in combinatorial libraries used in directed evolution.

PMID- 12813897
TI  - Computational methods for sequence mapping of large combinatorial libraries and
      deduced sequence signatures.
AB  - Here we describe a computational approach for the high-throughput sequence
      mapping of combinatorial libraries obtained by DNA shuffling. Original algorithms
      and their software implementation were developed for the automated and reliable
      analysis of hybridization data of differentially labeled oligonucleotide probes
      with PCR products spotted on DNA microarrays. This novel approach allows a
      context-dependent sequence attribution tolerant to fluctuations in experimental
      conditions and is well adapted to hybridization signals of variable qualities
      resulting from high-throughput PCR amplification from colonies. In addition, the
      analysis permits the calculation of sequence signatures that are characteristic
      of combinatorial library structure, defects, and diversity. The approach is of
      interest for the characterization and the equalization (library reduction to
      nonredundant structures) of combinatorial libraries involved in directed
      evolution and could be extrapolated to high-throughput polymorphism analysis.

PMID- 12813898
TI  - The LightTyper: high-throughput genotyping using fluorescent melting curve
      analysis.
AB  - Instrumentation, chemistry, and software for high-throughput genotyping using
      fluorescent melting curves are described. The LightTyper system provides post
      amplification genotyping within 10 min using samples in 96- or 384-well
      microplate formats. The system is homogenous because all reagents are added at
      the beginning of the reaction and there is no sample manipulation between
      amplification and genotyping. High-resolution melting curves are achieved by slow
      and steady heating. As samples are heated, panels of blue light-emitting diodes
      excite the probes, and fluorescence emission is acquired with a cooled charge
      coupled device camera. A variety of probe chemistries are compatible for
      genotyping on the LightTyper, including dsDNA dyes, single-labeled probes, and
      fluorescence resonance energy transfer systems. Genotyping is performed
      automatically, and each sample is given a score reflecting the similarity of the
      genotype to the standards provided. Standard genotypes can be selected from
      within the run or imported from other files. Samples and genotypes can be grouped
      to allow multiple-allele detection on one or many samples. The utility of the
      LightTyper is illustrated by genotyping samples for the Factor V Leiden mutation
      and for mutations in the CFTR gene.

PMID- 12813899
TI  - Novel protein kinase inhibitors: SMART drug design technology.

PMID- 12813900
TI  - Examination of the computed molecular properties of compounds selected for
      clinical development.
AB  - We have conducted a systematic evaluation of the calculated molecular properties
      of compounds in clinical development and have found that the development process
      selects for compounds that have certain computed physical properties. In
      particular, as the stage of development progresses, compounds that are advanced
      have lower calculated octanollwater partition coefficient (ClogP), polar surface
      area, and molecular weight. The findings of this study provide guidance for
      combinatorial library design and lead selection, which may enhance the chance for
      ultimate success in lead optimization.

PMID- 12813901
TI  - Strategies and methods in the identification of antagonists of protein-protein
      interactions.
AB  - The identification of antagonists of protein-protein interactions is a critical
      challenge to the pharmaceutical industry. The selection of a protein target,
      which is amenable to antagonism, is the first of many decisions that determine
      the success of these efforts. In addition, the definition of strategies and the
      development and application of methodologies appropriate to that target will be
      vital to the success of efforts to identify antagonists of a protein-protein
      interaction. An analysis of current approaches to the identification of lead
      molecules demonstrates that a search for competitors of a known binder is the
      basis of traditional screening as well as more modern approaches based on
      structure activity relationship (SAR) by nuclear magnetic resonance (NMR),
      molecular fragments, rational design, and tethering. The latter methods employ a
      structural perspective, throughout the discovery and optimization of a lead, to
      provide the practitioner with some control over the success of the process.

PMID- 12813902
TI  - Memorial. Hadley L. Conn Jr. 1921-2000.

PMID- 12813903
TI  - Memorial. David P. Earle, M.D. 1910-2002.

PMID- 12813904
TI  - Memorial. Ceylon Smith Lewis 1920-2001.

PMID- 12813905
TI  - Memorial. Gordon Steinbach Myers 1915-2000.

PMID- 12813906
TI  - Memorial. Edward C. Rosenow, Jr., MD 1909-2002.

PMID- 12813907
TI  - Memorial. Lynwood H. Smith 1930-2002.

PMID- 12813908
TI  - Memorial. Oscar A. Thorup, Jr. 1922-2002.

PMID- 12813909
TI  - President's address: "spacetime" and the academic and clinical missions of
      medical schools.

PMID- 12813910
TI  - Hospitalists as cure for hospitalism.
AB  - For much of recorded history, it was difficult to document that care in a
      hospital improved outcomes. In fact, the term "hospitalism" was coined to
      describe a variety of iatrogenic maladies that were acquired by hospitalized
      patients and that often were more deadly than the admitting condition itself. In
      the modern era, the presumed benefits of hospitalization are achieved at the
      expense of substantial resources, but even these high costs have not eliminated
      iatrogenic complications. The hospitalist movement, by which a specialized group
      of physicians cares for inpatients, especially on medical and pediatric services,
      has reduced costs, generally maintained the satisfaction of all participants, and
      appears to have improved the quality of care. Despite concerns about
      discontinuity of care, hospitalists are likely to become the dominant mode of
      inpatient care in the United States.

PMID- 12813911
TI  - Battle of the sexes: new insights into genetic pathways of gonadal development.
AB  - Sex determination is governed by a series of genetic switches that influence cell
      fate and differentiation during critical periods of gonadal development.
      Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal
      development provides an excellent opportunity to identify genes involved in
      differential organogenesis. The identification of the testis-determining gene,
      SRY (Sex-reversed on the Y), was a pivotal first step towards unraveling this
      genetic pathway. It is now clear that numerous other genes, in addition to SRY,
      are necessary for normal testis development. For example, human mutations in a
      variety of genes (SOX9, WT1, SF1) impair testis development. Murine models
      provide evidence for additional genes (Lhx9, Emx2, M33, Dmrt, Fgf9). This lecture
      will highlight insights gleaned from human mutations in the nuclear receptors,
      SF1 (Steroidogenic Factor1) (NR5A1) and DAX1 (Dosage-sensitive sex reversal,
      Adrenal hypoplasia congenita, X chromosome) (NR0B1). These studies reveal the
      exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and
      function in humans.

PMID- 12813912
TI  - E. coli heat-stable enterotoxin and guanylyl cyclase C: new functions and
      unsuspected actions.
AB  - Some E. coli cause diarrhea by elaborating heat-labile and heat-stable (ST)
      enterotoxins which stimulate intestinal secretion. E. coli ST's are small
      peptides which bind to intestinal luminal epithelial cell receptors. The ST
      receptor, one of a family of receptor-cyclases called guanylyl cyclase C (GC-C),
      is a membrane spanning protein containing an extracellular binding domain and
      intracellular protein kinase and catalytic domains. The intestine synthesizes and
      secretes homologous peptides, guanylin and uroguanylin. The kidney also
      synthesizes uroguanylin. ST, guanylin or uroguanylin binding to GC-C results in
      increased cGMP, phosphorylation of the CFTR Cl- channel and secretion.
      Proguanylin and prouroguanylin circulate in blood and bind to receptors in
      intestine, kidney, liver, brain etc. In the kidney, they stimulate the excretion
      of Na+ and K+. Study of GC-C "knock-out" mice reveal that GC-C is important to
      intestinal salt and water secretion, duodenal bicarbonate secretion, recovery
      from CCl4-induced liver injury, and to intestinal polyp formation in Min mice
      lacking GC-C.

PMID- 12813914
TI  - Immune evasion by herpes simplex virus type 1, strategies for virus survival.
AB  - Many viruses capable of persistent or recurrent infections have evolved
      strategies to evade host immunity. Viral evasion molecules target components of
      innate and acquired immunity, including complement proteins, natural killer
      cells, MHC Class I or Class II molecules and antibody. Our work focuses on HSV-1
      glycoproteins gC and gE that impair antibody and complement responses. gC
      inhibits complement activation by binding C3b and blocking activities mediated by
      this pivotal complement protein, while gE binds the IgG Fc domain, blocking Fc
      mediated activities, including complement activation and antibody-dependent
      cellular cytotoxicity. HSV-1 mutant viruses that lack the ability to bind C3b,
      IgG Fc, or both are much less virulent than wild-type virus in a murine model.
      These HSV-1 immunoevasins help explain the virus' ability to produce recurrent
      infections despite intact immunity. Strategies to prevent immune evasion may be
      required to develop successful HSV vaccines.

PMID- 12813913
TI  - Epithelial-mesenchymal transitions and the intersecting cell fate of fibroblasts
      and metastatic cancer cells.

PMID- 12813915
TI  - Biomedical informatics: precious scientific resource and public policy dilemma.
AB  - Biomedical informatics includes the application of computers, information
      networks and systems, and a growing body of scientific understanding to a range
      of problems. As skill in this field increases and as progress in virtually all
      modern biomedical science becomes more data intensive, informatics becomes a
      precious resource. Applications areas include access to knowledge, discovery in
      genomics, medical records, mathematical modeling, and bioengineering. At the same
      time, progress in informatics is deeply dependent on resolution of four major
      public policy issues: digital intellectual property rights, genetic testing
      protection, medical data privacy, and the role of biomedical data in the context
      of information warfare and homeland security.

PMID- 12813916
TI  - The Gordon Wilson Lecture. Lessons about the control of glucose homeostasis and
      the pathogenesis of diabetes from knockout mice.
AB  - The painstaking process of generating constitutive and conditional knockout mice
      has paid off handsomely. The roles of the insulin receptor and its intracellular
      substrates in insulin action has been established and begun to shed light onto
      some of the proteins less obvious functions. We have learned how genetic
      predisposition plays itself out in the oligogenic and heterogeneous pathogenesis
      of type 2 diabetes and how the balance of proteins can affect the efficiency of
      signaling both positively and negatively. The IRS knockout mice have taught us
      how these proteins provide unique and complementary signals in insulin action.
      From the tissue specific knockouts we have learned that [figure: see text]
      different tissues contribute uniquely to the pathogenesis of type 2 diabetes, but
      not always in the predicted way; that insulin resistance at different levels in
      the same tissue may produce different phenotypes; that tissues possess mechanisms
      of communication such that resistance in one tissue affects insulin signaling or
      metabolism in others; and that insulin has important effects in tissues not
      previously considered insulin responsive, including the brain and beta-cells. The
      result of this work has led us to develop new hypotheses about the nature of the
      insulin action network.

PMID- 12813917
TI  - Ketoacids? Good medicine?
AB  - D-beta-hydroxybutyrate, the principal "ketone" body in starving man, displaces
      glucose as the predominating fuel for brain, decreasing the need for glucose
      synthesis in liver (and kidney) and accordingly spares its precursor, muscle
      derived amino acids. Thus normal 70 kg. man survives 2-3 months of starvation
      instead of several weeks, and obese man many months to over a year. Without this
      metabolic adaptation, H. sapiens could not have evolved such a large brain.
      Recent studies have shown that D-beta-hydroxybutyrate, the principal "ketone", is
      not just a fuel, but a "superfuel" more efficiently producing ATP energy than
      glucose or fatty acid. In a perfused rat heart preparation, it increased
      contractility and decreased oxygen consumption. It has also protected neuronal
      cells in tissue culture against exposure to toxins associated with Alzheimer's or
      Parkinson's. In a rodent model it decreased the death of lung cells induced by
      hemorrhagic shock. Also, mice exposed to hypoxia survived longer. These and other
      data suggest a potential use of beta-hydroxybutyrate in a number of medical and
      non-medical conditions where oxygen supply or substrate utilization may be
      limited. Efforts are underway to prepare esters of beta-hydroxybutyrate which can
      be taken orally or parenterally to study its potential therapeutic applications.

PMID- 12813918
TI  - Isolated familial somatotropinomas: clinical and genetic considerations.
AB  - The majority of somatotropinomas (GH-secreting pituitary adenomas) are sporadic,
      through a few occur with a familial aggregation, either as a component of
      multiple endocrine neoplasia, type 1 (MEN1) or Carney complex, or when
      unassociated with other tumors, as isolated familial somatotropinomas (IFS). The
      latter is a rare disorder associated with loss of heterozygosity (LOH) on
      chromosome 11q13, the locus of the MEN1 gene. However, MEN1 sequence and
      expression are normal, suggesting the presence of another tumor suppressor gene
      within this locus that affects somatotrope proliferation. To further define the
      candidate interval, we performed haplotype and allelotype analyses in six
      families with IFS. The combined results have mapped the gene involved in the
      pathogenesis of IFS to a region of 9.7 Mb (7.6 cM) on chromosome 11q13.1-13.3.
      Identification of the IFS gene should provide new insight into the pathogenesis
      not only of this disorder but also of sporadic somatotropinomas.

PMID- 12813920
TI  - The color of hamburger: slow steps toward the development of a science-based food
      safety system in the United States.
AB  - Concerns about food safety have played a key role in the emergence of the public
      health system in the United States. Unfortunately, the food safety regulatory
      system that was established in the early part of the 20th century in response to
      these concerns has not kept pace with our advancing scientific knowledge. In
      1995, basic changes were made in the structure of the U.S. food safety regulatory
      structure, including implementation by USDA of the Pathogen Reduction: Hazard
      Analysis and Critical Control Point (HACCP) Systems; Final Rule for Meat and
      Poultry, from USDA's Food Safety and Inspection Service (FSIS); this was
      accompanied by creation of FoodNet, a sentinel surveillance system for active
      collection of foodborne disease surveillance data. The most recent FoodNet data
      show a 21% decline in the incidence of major bacterial foodborne diseases since
      implementation of the new regulations, a decrease paralleled by reductions in the
      frequency of contamination of meat and poultry with Salmonella. These data
      strongly support the public health importance of these regulatory changes.
      However, questions remain about the relative degree of responsibility of industry
      vs. the consumer in assuring safe food; the appropriateness of microbial
      standards for raw food products; and the directions that should be taken in the
      development of the "next generation" of food safety regulations.

PMID- 12813919
TI  - Decoding the LIM development code.
AB  - During development a vast number of distinct cell types arise from dividing
      progenitor cells. Concentration gradients of ligands that act via cell surface
      receptors signal transcriptional regulators that repress and activate particular
      genes. LIM homeodomain proteins are an important class of transcriptional
      regulators that direct cell fate. Although in C. elegans only a single LIM
      homeodomain protein is expressed in a particular cell type, in vertebrates
      combinations of LIM homeodomain proteins are expressed in cells that determine
      cell fates. We have investigated the molecular basis of the LIM domain "code"
      that determines cell fates such as wing formation in Drosophilia and motor neuron
      formation in chicks. The basic code is a homotetramer of 2 LIM homeodomain
      proteins bridged by the adaptor protein, nuclear LIM interactor (NLI). A more
      complex molecular language consisting of a hexamer complex involving NLI and 2
      LIM homeodomain proteins, Lhx3 and Isl1 determines ventral motor neuron
      formation. The same molecular "words" adopt different meanings depending on the
      context of expression of other molecular "words."

PMID- 12813921
TI  - A new approach to assessing function in elderly people.
AB  - Current functional assessment methods and measures of elderly people are limited
      in their ability to detect small decrements in function or in discriminating
      between different patterns of functional loss. Nor do they directly assess
      function in the patient's usual environment. Recent technological advances have
      led to the development of small, wearable microelectronic devices that detect
      motion, velocity and acceleration. These devices can be used to develop new tools
      for more precise monitoring, assessment, and prediction of function by
      characterizing the 'electronic signatures' of successful or unsuccessful task
      specific performance, and to allow for continuous assessment in a home
      environment. This presentation will summarize current efforts to translate new
      technologies into a clinical and research tool for improved assessment,
      monitoring, and prediction of function among older individuals.

PMID- 12813922
TI  - Clinical research: a tale of two studies.
AB  - Threats to the status of clinical research have been well documented in the past
      three decades, and the National Institutes of Health and the Congress have done
      much to alleviate them. But the relationships of academic investigators and
      pharmaceutical companies remain a treacherous area. This vital nexus, on which so
      much progress depends, must be carefully maintained. In this paper I present two
      examples of academic/pharmaceutical company collaborations, both in search of a
      similar drug. The cases illustrate both some important hazards and
      accomplishments of clinical research.

PMID- 12813923
TI  - Hormone replacement therapy: dilemmas in 2002.
AB  - About 6 million women in the United States are prescribed a combined estrogen
      progestin regimen during and after the menopause. The immediate benefits of
      hormone replacement therapy (HRT) are relief of menopausal symptoms. Doctors and
      their patients have long presumed that the benefits on cardiovascular disease and
      osteoporosis outweigh the possible increased risk of breast cancer or venous
      thrombosis. The Women's Health Initiative, a National Institutes of Health
      program, is the first study to compare HRT to placebo in healthy women. The July
      2002 report of increased cardiovascular events as well as increased breast cancer
      diagnosis in women on the HRT arm of the study brought widespread media coverage
      and has led to distress and confusion among women taking HRT. Women with a
      personal or family history of breast cancer pose a particular challenge to their
      physicians when they ask for advice about HRT.

PMID- 12813924
TI  - The internal challenges to medical education.
AB  - This presentation shall discuss the major "internal" challenges to medical
      education--that is, challenges to achieving effective medical teaching that have
      arisen from the evolution of the science and practice of medicine. These issues
      are defined as "internal" in that they reflect the internal evolution of the
      profession and of academic medical centers, independent of the perturbations in
      medical education we are presently experiencing as a result of the hostile
      external environment of health care. Examples of these internal challenges
      include the growing "bench-bedside gap," the traditional tensions at medical
      schools between teaching and research, and the need to adjust medical education
      to meet the challenges imposed by chronic diseases. The need for "internal"
      leadership from within the profession to help solve some of the "external"
      problems of medical education shall also be discussed.

PMID- 12813925
TI  - A California house call.

PMID- 12813927
TI  - Clinical studies linking fetal velocimetry, blood flow and placental transport in
      pregnancies complicated by intrauterine growth retardation (IUGR).
AB  - Our research has focused on two aspects of IUGR pregnancies: first, the changes
      in the fetal circulation which progress to fetal circulatory failure, and second,
      to reduced placental transport for amino acid and carbohydrate. There are
      sequential changes in fetal velocimetry for 8 different velocimetric indices.
      Measurements of blood flows in the fetal ductus venosus and in the umbilical vein
      have identified a subset of IUGR fetuses with significantly reduced umbilical
      blood flow, increased ductal shunt and reduced hepatic flow. Studies of placental
      amino acid transport in vivo have shown differences between normal and IUGR
      pregnancies which can be related to the velocimetry data. Clinical severity in
      FGR pregnancies can be related to 2 different sets of metabolic data. One is that
      of the glucose gradients across the placenta and another is the fetal/maternal
      enrichment ratios for amino acids. The implication and extension of these studies
      will be discussed.

PMID- 12813926
TI  - The Jeremiah Metzger Lecture. Pathogenesis of atherosclerosis: redox as a
      unifying mechanism.
AB  - Excessive production of reactive oxygen species (ROS) occurs in many diseases and
      oxidation may be a common disease mechanism generally. The original "oxidation
      hypothesis" concerning the pathogenesis of atherosclerosis was posited in the
      context of the putative central role of oxidized LDL in the process.
      Atherosclerosis has three major characteristic features: inflammation with
      accumulation of T-cells and, in particular, monocytes, which become lipid rich
      foam cells; remodeling of the arterial wall; and the non-random localization of
      lesions to areas of disturbed flow or of low shear stress. The evidence is
      reviewed that each of these characteristics can be attributed to excessive ROS,
      which are derived from cellular oxidases, especially, the NAD(P)H oxidases. This
      expanded concept of the central role of oxidation in the pathogenesis of
      atherosclerosis has led to a renewed and intense interest in the potential role
      of antioxidants in therapy. The vascular protective effects of existing drugs
      such as statins and ACE inhibitors that are not related to serum lipid
      alterations are attributed to their indirect but effective roles as antioxidants.
      These data as well as evidence that newly developed antioxidant drugs show
      promise, not only in experimental animals but also clinically, are reviewed.

PMID- 12813928
TI  - The EGF receptor family--multiple roles in proliferation, differentiation, and
      neoplasia with an emphasis on HER4.
AB  - The EGF Receptor (EGFR), the first transmembrane receptor tyrosine kinase cloned
      and sequenced, and its closely related family members HER2, HER3, and HER4, play
      myriad roles in mammalian growth and development. Receptor activation involves
      ligand binding to separate receptors followed by formation of active dimers.
      These receptors can signal as homodimers or they can subtly alter signaling
      output by heterodimerizing with other family members. Adding complexity, these
      receptors with varying specificity bind at least 10 ligands from two ligand
      families, the EGF and neuregulin/heregulin families. This signaling system's
      impact on human neoplasia is underscored by the following: i.) EGFR is
      overexpressed or activated by autocrine or paracrine growth factor loops in at
      least 50% of epithelial malignancies; ii.) HER2 is amplified and dramatically
      overexpressed in approximately 20%-25% or breast cancers; iii) HER3 and HER4 are
      variably expressed in breast and other cancers. Overexpression and/or activation
      of EGFR, HER2 and HER3 has been correlated with poor tumor prognosis; antibody
      and small molecule inhibitors of their activity are being tested as therapy in
      cancer patients. However, the signaling complexity engendered by four interacting
      receptors and ten ligands makes it difficult to definitively measure receptor
      signaling output in human tumors and even makes mechanistic studies of the
      family's role in normal physiology and neoplastic transformation a challenge. In
      spite of the literature's emphasis on growth control, activation by some EGF
      receptor family member ligands can produce tumor cell differentiation,
      characterized by growth cessation and differentiation gene product synthesis. The
      present work delineates a role for HER4 in breast cancer cell differentiation and
      demonstrates that HER4 is both necessary and sufficient to produce an anti
      proliferative signal. These

PMID- 12813929
TI  - Theodore E. Woodward Award. AAV-mediated gene transfer for hemophilia.
AB  - Our research efforts have been focussed on developing a gene transfer strategy
      for the treatment of the hemophilias. Hemophilia is an attractive target for
      studies in gene transfer because even small amounts of clotting factor can
      improve the clinical symptoms of the disease, the factor can be expressed in
      almost any tissue as long as it gains access to the circulation, and there are
      large and small animal models of the disease, so that promising approaches can be
      assessed for efficacy before moving into clinical studies (1). We have developed
      recombinant adeno-associated viral (AAV) vectors expressing blood coagulation
      Factor IX. AAV has a number of advantages as a gene transfer vector including: 1)
      the absence of viral coding sequences in the recombinant vector; 2) the ability
      to transduce a variety of non-dividing target cells, including liver, muscle and
      nervous system; 3) the ability to direct long-term expression of the transgene in
      immunocompetent animals. We have introduced AAV-F.IX vectors into skeletal muscle
      and liver, and shown long-term correction of the bleeding diatheses in both small
      and large animal models of hemophilia B (2-5). In the initial clinical trial,
      rAAV was introduced into skeletal muscle of subjects with severe hemophilia B.
      Results showed that the general characteristics of transduction were similar in
      mouse, canine and human muscle, and muscle biopsies of injected sites showed
      evidence of gene transfer and expression, but circulating levels of F.IX failed
      to reach the desired target of 3-10%. There were no serious adverse events
      associated with rAAV injection in skeletal muscle (6). Work has also proceeded on
      development of a liver-directed approach. Engineering of the expression cassette
      has resulted in better expression per particle, and circulating F.IX levels of 4
      12% have now been achieved in hemophilia B dogs treated with vector doses lower
      than those already administered in the clinical study in skeletal muscle (5).
      After extensive safety studies in mice, rats, hemophilic dogs and non-human
      primates, a Phase I study of an AAV-mediated, liver-directed approach to treating
      hemophilia B has begun. There were no acute toxicities associated with
      administration of vector to the first two subjects, but subsequently a PCR assay
      on the subjects' semen was found to be positive for vector sequences. After a
      period of weeks, the positive signal disappeared. These findings were distinct
      from those seen in pre-clinical animal studies. To gain a clearer understanding
      of the biodistribution of vector to the gonads, we undertook additional studies
      in rabbits and mice. These showed that, following intravascular delivery of
      vector, there is hematogenous dissemination to the gonads and gradual washout of
      vector over time. Direct transduction of germ cells does not appear to occur (7).
      Based on these and other safety studies, the clinical trial has now resumed. A
      goal of this work will be to determine whether the therapeutic levels achieved in
      a large animal model of hemophilia can be realized in humans.

PMID- 12813930
TI  - Theodore E. Woodward Award. HIV/AIDS, ethics, and medical professionalism: where
      went the debate?
AB  - The recent surge of dialogue about medical professionalism has largely ignored
      HIV/AIDS, perhaps because the ethical issues that abounded during the 1980s and
      early 1990s have become largely passe. Prior to the introduction of highly active
      antiretroviral therapy (HAART) in 1996, the care ethic for patients with HIV/AIDS
      depended heavily on compassion since effective treatment was unavailable.
      Moreover, physicians and other health care workers often assumed physical risks
      on behalf of patients. HAART transformed the care ethic for HIV/AIDS to one
      dependent mainly on medical competence. Reflecting on the epidemic, I propose a
      distinction between "basic" and "higher" professionalism. Basic professionalism
      requires discipline-specific competence, facilitated by adherence to the four
      cardinal virtues (prudence, temperance, justice, and courage). Higher
      professionalism brings into play the transcendent virtues: faith, hope, and-
      especially--love (compassion). Specific examples of "compassion" in the strict
      sense of "suffering with" include caring without adequate reimbursement, caring
      when one would rather be doing something else, and assuming emotional or physical
      risks on behalf of patients. The physicians and other health care workers who
      displayed such compassion in abundance between 1981 and 1996 deserve our
      remembrance as exemplars of a higher professionalism.

PMID- 12813931
TI  - Conflict of interest and the public trust: a dean's view.

PMID- 12813932
TI  - Recollections of infectious disease research in Guadalajara, 1948-50.

PMID- 12813933
TI  - What's a new safety manager to do?

PMID- 12813934
TI  - Boning up. Seeing surgical demonstrations helps practitioners understand how a
      worker recovers from a wrist injury or condition.

PMID- 12813935
TI  - Developing effective warnings for the workplace.

PMID- 12813937
TI  - How to run an incentive.

PMID- 12813936
TI  - Vision protection. Backing the brands.

PMID- 12813938
TI  - Reward cards motivate.

PMID- 12813939
TI  - Evaluating the effectiveness of safety training.

PMID- 12813940
TI  - Preventing workplace violence.

PMID- 12813941
TI  - Faster detection & better vaccines.

PMID- 12813942
TI  - Principles of physiology and respirator performance.
AB  - Several respirator performance criteria are set to satisfy the physiological
      requirements of the worker. In particular, Ve and PFI must be understood and used
      appropriately in the design process. Filtration principles and the nature of
      workplace aerosols must also be understood to determine appropriate test
      conditions for particulate respirator filters. Current filter test criteria
      assure that significant aerosol penetration will not occur in the workplace. It
      is unlikely that existing positive-pressure respirators can assure positive
      pressure in the breathing zone at all times for all wearers. High, unsustainable
      work rates and activities such as running in place have been shown to cause
      negative-pressure excursions under laboratory and workplace conditions. Because
      these excursions are brief and infrequent for today's respirators, both logic and
      performance measurements indicate they have a negligible effect on exposure.
      Filters could no doubt be designed to pass extreme test criteria. Similarly, it
      may be possible to design positive-pressure respirators to maintain positive
      pressure 100 percent of the time for all users. However, it is likely that cost
      and size would increase and comfort could decrease. Further, available evidence
      demonstrates that today's respirators provide their expected level of protection
      when properly selected, used, and maintained. As such, there is no demonstrated
      need for radical design changes.

PMID- 12813943
TI  - Building corporate castles, Part 2.

PMID- 12813944
TI  - Defibrillators & CPR. More than meets the eye.

PMID- 12813945
TI  - A hearing conservation program for coal miners.

PMID- 12813946
TI  - Haven't got time for the pain.

PMID- 12813947
TI  - Justifying the cost of height-adjustable office work surfaces.
AB  - To defeat objections about "expensive" ergonomic product solutions, think like
      your colleagues do in facilities, real estate, human resources, and IT, and more
      clearly communicate the broader benefits of adjustable office furniture. The
      question shouldn't be "How are we going to pay for an improved office
      environment?" The better questions are, "Can we identify the ways that we already
      pay for a poor office environment?" and "Can we afford to keep paying?".

PMID- 12813948
TI  - Critical success factors for ergonomics processes.

PMID- 12813949
TI  - New options for monitoring.

PMID- 12813950
TI  - Construction safety. Questions of competence.

PMID- 12813951
TI  - Hand protection. Creating a cut-free workplace.

PMID- 12813952
TI  - Gloves that last.

PMID- 12813953
TI  - Legal and regulatory issues in hospital laboratory outreach and partnering
      arrangements.
AB  - An independent laboratory's joint venture with a chain of five nonprofit
      hospitals unraveled in 1999. Despite substantial management control over the
      joint venture and 3 years spent investing in and managing a massive consolidation
      project, the laboratory operator was ousted by the hospital group in favor of a
      national laboratory competitor. In the process, it lost the $6 million commercial
      laboratory business it brought to the joint venture. The laboratory operator sued
      the hospital group for destroying its business. Were the hospital's actions
      legal? Could the laboratory operator have protected itself better? Although by no
      means the only causes of this disaster, regulatory restrictions and uncertain
      contract terms contributed to the problems experienced by the laboratory
      operator.

PMID- 12813954
TI  - Patient-provider connectivity and the role of e-health.
AB  - Patient-provider connectivity (PPC) offers innovative approaches to control
      costs, improve quality, and sustain a healthy workforce. The application of e
      commerce to health care is one facet of PPC and provides solutions to educating,
      informing, and more efficiently using scarce resources to sustain the nation's
      health. Technology is available to provide real-time access to clinical results,
      medical records, health-care providers, and other time-sensitive patient
      information. This is the first article in a series on PPC that explores the
      application of e-commerce to the health-care industry from the consumers' and
      providers' points of view and examines and assesses trends and data from various
      interdisciplinary sources and studies. Two models exemplifying PPC are explored
      including the Science Business & Education, Inc., proof-of-concept patient
      demonstration project, and the emerging application of peer-to-peer (P2P)
      technology. PPC promises to improve efficiency, facilitate communication between
      physician and patient, monitor compliance with medical regimens, and positively
      affect the quality of health care provided and the overall health of the patient.
      Future articles will address the growth of telemedicine, issues of
      confidentiality and e-risk, and other PPC applications.

PMID- 12813955
TI  - Networking: a long-term management strategy.
AB  - As we face a changing health-care landscape of mergers and acquisitions during
      these tough economic times, it is more important than ever to cultivate a network
      of individuals who can assist you in your career development efforts. How do you
      manage your career in a shrinking economy? What is networking and how can you use
      it to enhance your career and professional competencies? Many myths surround the
      networking process; this article clarifies those misperceptions and tells you the
      truth about networking and the positive results you can achieve. Networking can
      be used to get a new job, but it has much wider application as a long-term career
      management strategy. Learn how you can manage your own career while building
      professional relationships and coaching your employees.

PMID- 12813956
TI  - Using Monte Carlo simulation to assess and manage risk in the clinical
      laboratory.
AB  - Managers often are asked to consider opportunities that involve risks.
      Traditional approaches to evaluating uncertainty fall short of providing a
      comprehensive view of possible outcomes. Risk analysis techniques using Monte
      Carlo simulation offer a more sophisticated approach that can help the manager
      better understand and manage those risks. This article discusses the advantages
      of using risk analysis and provides three illustrations of how this approach can
      aid in decisionmaking in the clinical laboratory setting.

PMID- 12813957
TI  - Hidden nuggets: nautical archeology and laboratory management.
AB  - Although the professions of nautical archaeology and clinical laboratory
      management seem to involve different bodies of knowledge, many of the principles
      and truisms of archaeology correlate to the art of laboratory management. On two
      occasions, I have been a member of a team excavating a 350-year-old shipwreck off
      the north shore of the Dominican Republic. I have illustrated those experiences
      to demonstrate that these seemingly disparate professions share frustrations that
      interfere with the pursuit of useful knowledge as well as successes that lead to
      new knowledge.

PMID- 12813958
TI  - Managing risk for middle managers.

PMID- 12813959
TI  - Case studies in ethics 1993-2003: a 10-year retrospective.

PMID- 12813960
TI  - Common cent$ 12: a hard day's night--work and the theory of the firm.

PMID- 12813961
TI  - Biosafety considerations in laboratory design.

PMID- 12813962
TI  - Growing your own: a long-term solution to your staffing needs.

PMID- 12813963
TI  - Entering new territory: direct to patient testing expands laboratory's offerings.

PMID- 12813964
TI  - Paying for quality: not-for-profit program promotes rewards for performance.
AB  - Two years ago, the Institute of Medicine report Crossing the Quality Chasm issued
      a challenge to find ways to reduce the "burden of illness, injury, and
      disability" in the United States while "improving the health and functioning" of
      the population. Last month, a new program called Bridges to Excellence--created
      by a coalition of major employers, physicians, health plans, and others--was
      unveiled to meet that goal by rewarding physicians through incentive payments
      related to performance.

PMID- 12813965
TI  - Reasons for crowded EDs vary among hospitals, communities, GAO says.
AB  - While no single issue explains the main reason for overcrowding in hospital
      emergency departments (EDs), the inability to transfer emergency patients to
      inpatient beds quickly once a decision to admit them has been made appears to be
      an important contributing factor at many hospitals, according to a new report on
      ED overcrowding from the U.S. General Accounting Office.

PMID- 12813966
TI  - Health profession education needs overhaul to improve quality and safety, IOM
      says.

PMID- 12813967
TI  - [Dependent on sex, gambling, sports or work. Always single minded].

PMID- 12813968
TI  - [When you cannot prescribe abstinence: help the patient achieve a stable sense of
      self worth (interview by Dr. Judith Neumaier)].

PMID- 12813969
TI  - [Family physicians lobbyists cry--but: internal medicine lives!].

PMID- 12813970
TI  - [On the track of Schoenlein-Henoch purpura. Abdominal pain with renal failure].

PMID- 12813971
TI  - [Confusion of wild garlic/meadow saffron/lily of the valley. That is even beyond
      the lay person].

PMID- 12813972
TI  - [Evaluation of endoscopic methods. Minimal invasive surgery in goiter? (interview
      by Michael Koczorek)].

PMID- 12813974
TI  - [Determining the diagnosis from the pain pattern. Brief and stabbing or chronic
      and dull?].
AB  - For the neurological differential diagnosis of facial pain, symptomatic pain must
      be differentiated from the so-called primary pain syndromes. Trigeminal neuralgia
      is usually readily diagnosed on the basis of the typical history. The treatment
      of choice is carbamazepine. If this fails, invasive options are available.
      Atypical facial pain should be diagnosed only when all known primary and
      secondary pain syndromes have been excluded. Treatment is difficult and comprises
      the administration of tricyclic antidepressants. Cluster headache and chronic
      paroxysmal hemicrania each has an unmistakable temporal course. Although the
      etiology remains unknown, specific therapeutic options are available. The Tolosa
      Hunt syndrome is presumably caused by a granuloma in the cavernous sinus, and
      treatment is effected with corticosteroids. Painful craniomandibular dysfunction
      (CMD) is often misinterpreted as atypical facial pain.

PMID- 12813973
TI  - [Also consider sinusitis in facial pain: wisdown tooth, tumor, acute parotitis].
AB  - In numerous cases of head and facial pain, the underlying causes are found to be
      ENT problems. The most common cause of pain affecting the forehead and mid-facial
      region is acute sinusitis, in which the sphenoidal sinus is more commonly
      affected than previously assumed. Pain in the oral-facial region is largely due
      to disorders of the masticatory apparatus, but inflammatory diseases of the oral
      mucosa, abscesses or the so-called Eagle syndrome may also be involved. An
      accurate history and a clinical examination often points the physician in the
      right direction. To establish an accurate diagnosis, endoscopy of the upper
      airways and digestive system, together with ultrasonography, are usually
      required, followed, where necessary, by a radiological and NMR work-up, and
      puncture or biopsy. Provided that an accurate diagnosis has been established and
      multidisciplinary cooperation is available, the therapeutic options are usually
      effective.

PMID- 12813975
TI  - [Myoarthropathy of the temporomandibular joint and masticatory muscles. Pain
      therapy management and relaxation instead of aggressive surgery].
AB  - Temporomandibular pain is often characterized by a mismatch between symptoms and
      findings. The dentist's well-established therapeutic strategies for the
      management of acute pain are therefore frequently not effective in patients with
      painful temporomandibular disorders (TMD). Instead, dentists should apply the
      tried and tested principles that are applied in general medicine to the diagnosis
      and treatment of musculoskeletal pain (e.g. arthritic pain or fibromyalgia). When
      consulted by patients with rheumatic diseases, physicians should routinely
      enquire whether they also experience temporomandibular pain.

PMID- 12813976
TI  - [SARS--the facts. Transmission, diagnosis and managing suspected cases].
AB  - Severe Acute Respiratory Syndrome (SARS) is a new infectious disease that, in the
      short period between 1 February and 24 April 2003, has been diagnosed in more
      than 4000 patients. Its origin was traced to Guandong, a province in southeast
      China. The culprit organism was identified as a new coronavirus. The clinical
      presentation is unspecific and includes fever, respiratory symptoms, lymphopenia
      and pulmonary infiltrates on X-ray. Essential steps to prevent further
      dissemination of the virus are rapid identification, and treatment in an
      isolation unit. Despite all the international efforts and the rapid progress in
      the investigation of SARS coordinated by the World Health Organization (WHO), the
      epidemic has not yet been brought under control.

PMID- 12813977
TI  - [Preventing infarct in the diabetic patient. Lowering blood glucose and HbA1c are
      not enough].

PMID- 12813978
TI  - [Pharmacogenetics and pharmacogenomics. Searching for individual antihypertensive
      therapy concepts].

PMID- 12813979
TI  - [Back pain of a different kind].

PMID- 12813981
TI  - [Nicotine replacement therapy. Sucking instead of smoking].

PMID- 12813982
TI  - [Long-term oral coagulation. Self monitoring prevents complication].

PMID- 12813980
TI  - [Instead of occupational right the law regarding remedy advertising becomes a
      pitfall. Physician image forbidden in general practice brochures?].

PMID- 12813983
TI  - [Therapy of hypertension in patients with atrial fibrillation. Sartan is superior
      to beta-blocker].

PMID- 12813984
TI  - [Basic immunization hexvalent vaccine. Are there differences between vaccines?].

PMID- 12813985
TI  - [When patients decline treatment of depression. Phytotherapy drugs are often
      better accepted].

PMID- 12813986
TI  - [Because fee settlement means are not widely known. Deficits in hepatitis C
      therapy].

PMID- 12813987
TI  - [For patients with osteoporosis-induced fracture the emergency brake must be
      pulled. Every 4th patient as a recurrence in the following year].

PMID- 12813988
TI  - [Preventing recurrence after alcohol withdrawal treatment with drugs. Reducing
      the drive to drink].

PMID- 12813989
TI  - [Often test the lungs of your patients! "Each patient should know his FEV1
      value"].

PMID- 12813990
TI  - [Daily sildenafil tablet at night, can erectile impotence be cured permanently
      this way?].

PMID- 12813991
TI  - [Continuous once a day treatment with sildenafil: daily sex prevents the "aging
      penis"].

PMID- 12813992
TI  - [44. Normalizing blood lipids--with diet, sports and antilipemic agents].

PMID- 12813993
TI  - [Low molecular weight heparin certoparin. Clear simplification of thrombosis
      treatment].

PMID- 12813994
TI  - [Possible effect low molecular weight heparin on survival time. New chances for
      cancer patients?].

PMID- 12813995
TI  - Men, women, and war: a physician's view.

PMID- 12813996
TI  - Genetic testing: speaking up for women's privacy interests.

PMID- 12813997
TI  - Increased estrogen-dependent expression of calcineurin in female SLE T cells is
      regulated by multiple mechanisms.
AB  - OBJECTIVE: Calcineurin is a key mediator of T cell activation. Previous studies
      in our laboratory showed a dose-dependent and hormone-specific increase in
      calcineurin expression in the T cells from females with systemic lupus
      erythematosus (SLE). This study investigates whether the estrogen-dependent
      increase in calcineurin expression is due to stabilization of the messenger RNA
      (mRNA). METHODS: T cells from female patients with SLE and controls were cultured
      for 18 hours in a serum-free medium with and without estradiol-17 beta (10(-7)
      M). Some T cells were activated by further culture on anti-CD3-coated plates.
      Actinomycin D (25 micrograms/mL) was added to some cultures to inhibit new mRNA
      synthesis. Calcineurin mRNA stability was assessed by reverse-transcription
      polymerase chain amplification. RESULTS: Resting SLE (n = 9, P = .59) and normal
      (n = 5, P = .90) T cells showed no significant differences in mRNA stability in
      response to estradiol. Calcineurin mRNA was not significantly stabilized in
      activated SLE (n = 10, P = .12) or activated normal (n = 8, P = .09) T cells in
      response to estradiol. However, the amount of calcineurin mRNA stabilized in
      activated normal T cells (n = 8) was significantly greater (P = .02) compared
      with SLE T cells (n = 10) only after culture in medium without estradiol.
      CONCLUSIONS: These findings highlight the complex gene regulatory mechanisms
      underlying the differential action of estrogen on SLE T cells. Furthermore, the
      data indicate that increased calcineurin expression in SLE T cells is not due
      solely to estrogen-dependent stabilization of the message, and probably involves
      additional transcriptional regulatory mechanisms.

PMID- 12813998
TI  - Depression in mechanical function following ischemia in the female rat heart:
      role of fatty acids and altered mitochondrial respiration.
AB  - BACKGROUND: Clinical studies have shown that the incidence of myocardial
      infarction is lower in women compared to men. However, following a myocardial
      infarct, women are at increased risk of developing ventricular dysfunction.
      OBJECTIVE: High levels of free fatty acids, observed in the clinical setting of
      ischemia, impair recovery of mechanical function during reperfusion of ischemic
      hearts. This study was designed to determine whether hearts from female rats are
      more sensitive to ischemia than male hearts when supplied with relevant levels of
      fatty acids. METHODS: Hearts from male and female Sprague-Dawley rats were
      isolated and perfused in the working mode with 5.5 mM glucose and 50 microU/mL
      insulin alone or in the presence of 1.2 mM palmitate. Cardiac function, expressed
      as heart rate-pressure product (RPP), was measured under preischemic conditions
      and during reperfusion following a period of transient global ischemia. RESULTS:
      Following the ischemic insult, RPP of male hearts returned to preischemic levels
      regardless of the substrates used. RPP of female hearts perfused with glucose
      alone also recovered to preischemic function. However, in female hearts perfused
      with the fatty acid, recovery of RPP was significantly lower compared to the
      female hearts perfused with glucose alone. In these hearts, recovery during
      reperfusion was only approximately 60% of preischemic function. CONCLUSION: Our
      results indicate that the sensitivity of the female myocardium to postischemic
      dysfunction is enhanced in the presence of fatty acids, suggesting that a gender
      effect on recovery of cardiac function following ischemia exists.

PMID- 12813999
TI  - Prevalence of asymptomatic Clostridium difficile colonization in a nursing home
      population: a cross-sectional study.
AB  - OBJECTIVE: We conducted a cross-sectional study to determine the prevalence of
      asymptomatic Clostridium difficile in a nursing home population. METHODS:
      Inclusion criteria for the study required that the subjects be residents of the
      facility for more than 1 month. Exclusion criteria included: (1) patients who
      developed C. difficile infection within 2 months prior to stool collection; (2)
      metronidazole or vancomycin therapy within 2 months prior to stool collection;
      (3) past surgical history of colectomy; and (4) possible signs and symptoms of
      active C. difficile infection. RESULTS: The prevalence of asymptomatic C.
      difficile infection in this population was 5%. There was no significantly higher
      prevalence of asymptomatic C. difficile based on age, race, length of stay,
      gender, diabetes, renal failure, history of cancer, recent antibiotic use,
      gastric tube, histamine2 blocker/proton pump inhibitor use, Foley catheter, or
      dementia. CONCLUSIONS: The prevalence of asymptomatic C. difficile in this
      population is similar to previously studied populations. Further research should
      follow a cohort of asymptomatic individuals with C. difficile to determine if
      colonization may be protective against symptomatic infection.

PMID- 12814000
TI  - Mental illness and menopause: a patient and family perspective.
AB  - BACKGROUND: Menopause is a significant biological event in the life of every
      woman, including women with mental disorders. This brief report describes the
      results of a survey of 39 patients with mental illness and their family members
      regarding perceived effects of menopause on mental illness. METHODS: The survey
      was distributed to participants attending a National Alliance for the Mentally
      Ill educational presentation on menopause and mental health. RESULTS: Most
      participants (15/39; 38.5%) had depression or had a family member with
      depression. Groups with other mental disorders were less represented, with 8/39
      (20.5%) having schizophrenia, 6/39 (15.4%) having bipolar illness, and 10/39
      (25.6%) having other disorders such as anxiety disorders or personality
      disorders. The mean age of the individuals/family members with mental illness was
      51.2 years. Most participants (21/39; 53.8%) felt that menopause might be
      affecting their emotional symptoms or those of their family members, while 11/39
      (28.2%) felt that their illness or their family member's illness was worse
      because of menopause or approaching menopause. There was a trend for perception
      of menopause affecting mental illness to be stronger among individuals with
      bipolar illness and depression, as compared to individuals with schizophrenia and
      other disorders (P = .052). CONCLUSIONS: Menopause is a significant life event
      among women with mental illness. Nearly 30% of individuals affected by mental
      illness perceive menopause to worsen symptoms of mental illness.

PMID- 12814001
TI  - Gender analyses of nursing home residents with multiple sclerosis.
AB  - OBJECTIVE: To present gender comparisons of residents with multiple sclerosis
      (MS) at admission to nursing facilities, including demographic characteristics,
      health measures, and treatments. METHODS: We analyzed 13,998 admission
      assessments in the Minimum Data Set for residents with MS recorded between June
      23, 1998 and December 31, 2000. RESULTS: Although both male and female residents
      with MS tended to have severe disability, there were significant gender
      differences in measures of activities of daily living (ADL) dependency and
      disability, with males slightly more likely to exhibit total ADL dependence and
      greater loss of voluntary movement. Females with MS tended to have significantly
      better cognitive performance and better communication abilities than males with
      MS. There were significant gender differences in pain symptoms among residents,
      with one-third of females and one-fifth of males experiencing daily pain.
      Depression was the most common comorbidity among residents with MS, with females
      significantly more likely to have this diagnosis. Although females with MS were
      slightly more likely to have depression or anxiety disorder, males with MS were
      slightly more likely to receive mental health services. CONCLUSIONS: These
      analyses demonstrate that many nursing facilities need to improve pain management
      and mental health care provided to residents with MS, especially to females.

PMID- 12814002
TI  - Decisions, decisions, decisions.

PMID- 12814003
TI  - Setting the record straight.

PMID- 12814004
TI  - More about Medicare.

PMID- 12814005
TI  - More nonsense.

PMID- 12814006
TI  - Protect your investment.

PMID- 12814007
TI  - Charting your course into the future.

PMID- 12814008
TI  - Making the move that's right for you.

PMID- 12814009
TI  - How to make money even when you're out of the office!

PMID- 12814010
TI  - Shall we dance? Taking a partner into your practice.

PMID- 12814011
TI  - The power of time.

PMID- 12814012
TI  - UB researchers find poor oral health adds to disease burden of alcoholics.

PMID- 12814013
TI  - ['Body-packer' syndrome: an important disease with forensic-medical aspects].
AB  - A 45-year-old man called for the hospital in a confused and anxious state.
      Another man of around 30 walked into a hospital sweating and complaining of
      abdominal pain, and subsequently suffered several epileptic seizures and died
      before being recognised as a body packer. A 39-year-old man suffered an epileptic
      seizure on the aeroplane and a 21-year-old man was found dead, having suffered
      from abdominal pain the previous day. All were found to have swallowed cocaine
      packets. The two eldest men underwent emergency surgery: one died as the result
      of cocaine intoxication and one recovered. Body packers, people carrying cocaine
      packets in their bodies, are arriving in Europe in increasing numbers, mainly
      from South America. Body-packer syndrome consists of intestinal occlusion or
      potentially lethal intoxication caused by rupture of the packets. Awareness of
      the body packers' circumstances and the clinical signs of body-packer syndrome
      makes early recognition possible. In Amsterdam, the identification of body
      packers after arrival at the airport by the Schiphol-team and the medical follow
      up by the Forensic Medicine Department of the Municipal Health Service of
      Amsterdam, result in a relatively low mortality risk. Early detection of
      intoxication will save lives.

PMID- 12814014
TI  - [Staphylococcus aureus, a successful pathogen].
AB  - Staphylococcus aureus is a dreadful pathogen for mankind, causing boils,
      abscesses, wound infections, osteomyelitis, septicaemia, endocarditis, pneumonia,
      toxic shock syndrome, scalded skin syndrome, and food poisoning. The development
      of penicillin-, methicillin-, and vancomycin-resistant strains shows that S.
      aureus has an enormous adaptive power. Most methicillin-resistant strains of S.
      aureus (MRSA) are hospital-acquired, although an increasing number are reported
      to be community-acquired. A limited number of clones of MRSA have spread all over
      the world. Since most community-acquired MRSA can be traced back to some contact
      with health care, MRSA can still best be combatted by control measures in health
      care institutions. In this respect, the Netherlands and Scandinavian countries
      have been very successful so far. S. aureus has many virulence factors at its
      disposal: structural components, enzymes and three types of toxins. Panton
      Valentine leukocidin (PVL) has received attention as a factor causing severe
      pneumonia with high mortality. A strain combining methicillin resistance and PVL
      has spread through France. Recently, the genome of an MRSA strain has been
      unravelled. Its structure illustrates how well S. aureus can adapt itself and
      acquire properties of other microorganisms. This genetic knowledge may lead to
      new strategies to combat S. aureus.

PMID- 12814015
TI  - [The limited detection of lung cancer on chest X-rays].
AB  - In a study of everyday clinical practice, the diagnosis 'lung cancer' was not
      made on the chest X-ray initially in one-fifth of the cases, even though in
      retrospect the lesions had been visible on the chest X-ray. In nearly half of
      these cases, the diagnosis had been missed at least twice on succeeding X-rays of
      the patient in question. Most often, superimposed structures are responsible for
      having missed lesions on the chest X-ray; this was the case in 71% of the
      patients in whom a lesion was missed. The intra- and inter-observer variation in
      the detection of small tumours on the chest X-ray are quite large (kappa: 0.38
      and 0.48, respectively). Providing clinical information or previous chest X-rays
      for purposes of comparison does not improve the observer performance. Separate
      evaluation by two assessors ('double reading') also does not improve the results
      significantly. Simultaneous evaluation ('dual reading') improves the sensitivity
      slightly (from 28 to 37%), but has hardly any effect on the specificity (from 93
      to 92%), thus improving the results somewhat. The results with computed
      tomography are much better (high sensitivity but low specificity). A CT-scan of
      the chest seems indicated in case of a suspicion of lung cancer and/or when there
      is a (slight) suspicion of lung cancer on the basis of the chest X-ray.

PMID- 12814016
TI  - [Intrahepatic cholestasis of pregnancy].
AB  - Intrahepatic cholestasis of pregnancy occurs mainly in the final months of
      pregnancy, and is characterised by pruritus. Foetal morbidity and mortality are
      increased. The disorder is probably caused by a genetic defect in hormonal
      metabolism which becomes manifest during the altered hormonal balance in
      pregnancy. The total serum bile acid concentration is the diagnostic hallmark of
      the disease. Other routine laboratory tests have a low sensitivity and
      specificity. An active obstetric management with routine foetal assessments,
      caesarean section if the foetal condition worsens, and termination of the
      pregnancy at 37-38 weeks, probably prevents a large proportion of complications.
      Ursodeoxycholic acid treatment should be considered especially in patients with
      severe pruritus or complications in previous pregnancies.

PMID- 12814017
TI  - [Thrombophilia and the prevention of thromboembolic complications during
      pregnancy and the puerperium].
AB  - Deep vein thrombosis is one of the main causes of maternal death in the Western
      world, pulmonary embolism, as a complication, being the immediate cause of death
      in most cases. Deep vein thrombosis is the end result of several, partly
      interrelated, inherited and acquired risk factors. Thrombophilia is the overall
      name for a number of specific abnormalities resulting in an increased tendency
      towards haemocoagulation. In order to reduce the morbidity and mortality caused
      by thromboembolic complications in pregnant women, all women who want to become
      pregnant should be screened for risk factors in order to assess the a priori risk
      of venous thrombosis. Based on the individual thrombosis history and the presence
      of thrombophilia, a prophylactic policy can be determined for every pregnant
      woman. Currently, there are no data available from prospective and randomised
      trials assessing the effects of anticoagulants in pregnant women with
      thrombophilia.

PMID- 12814018
TI  - [Diagnostic image (141) Nodules in a patient with rheumatoid arthritis.
      Multicentric reticulohistiocytosis as a paraneoplastic manifestation].
AB  - A 59-year-old man presented with polyarthritis and noduli on fingers and buccal
      mucous membrane due to multicentric reticulohistiocytosis. This was a
      paraneoplastic manifestation of a renal cell carcinoma, and regression of noduli
      was seen after nephrectomy.

PMID- 12814019
TI  - [Self-monitoring by patients with type-2 diabetes mellitus one year after
      initiation: user errors in a quarter of cases].
AB  - OBJECTIVE: To inventory the errors made during self-monitoring of blood-glucose
      values by diabetes patients. DESIGN: Descriptive. METHOD: In patients with type-2
      diabetes mellitus who were registered with the West-Friesland Diabetes Care
      System (the Netherlands) during the period 1 April 2000-30 April 2001, and who
      had been monitoring their own glucose values for more than one year, checks for
      meter and user errors were carried out. When the patients first started using the
      glucose meter they were instructed by a diabetes nurse. The checks were carried
      out by a specially-trained nurse using a specifically-designed check list.
      RESULTS: Of the 249 participating patients, 123 were female and the mean age was
      69 years. User errors in self-monitoring of the blood glucose occurred in 59
      patients (24%). These primarily involved the use of expired or incorrect glucose
      strips (n = 17) and incorrect serial numbers (n = 16). No errors were made while
      placing the drop of blood on the glucose strip. Almost all patients had questions
      about the use of the glucose meter. CONCLUSION: Systematic checks of patient self
      monitoring detected user errors in 24%.

PMID- 12814020
TI  - [HIV-infection and AIDS in the Netherlands: prevalence and incidence, 1987-2001].
AB  - OBJECTIVE: To describe the results of HIV-surveillance activities in the
      Netherlands between 1987 and 2001. DESIGN: Descriptive. METHOD: Data were
      obtained from HIV-surveillance at STI-clinics, laboratory-surveillance in the
      region Arnhem, surveillance among injecting drug users, the AIDS-notification,
      STI-registration and the Amsterdam cohort studies on HIV/AIDS. RESULTS: In the
      Netherlands, the highest HIV-prevalences were found among injecting drug users (1
      26%) and homo- and bisexual men (0-17%). In these high-risk populations, an
      increase in HIV-prevalence and--incidence, respectively, was found among
      injecting drug users in Heerlen and homosexual men (> 35 years of age) in
      Amsterdam. The HIV-prevalence was lower among heterosexuals in the Netherlands (0
      2%). However, in certain local populations an increase was seen. In both
      Amsterdam and Rotterdam, the HIV-prevalence was higher in individuals tested
      anonymously than in those tested by name. CONCLUSION: Local increases in HIV
      infections have been observed recently, in both high- and medium-risk
      populations.

PMID- 12814021
TI  - [Fatal pneumonia in an adolescent due to community-acquired methicillin-resistant
      Staphylococcus aureus positive for Panton-Valentine-leukocidin].
AB  - A 15-year-old girl developed a severe Staphylococcus aureus pneumonia following
      an influenza virus infection. The patient was admitted to a paediatric intensive
      care facility because of respiratory and circulatory failure. Despite aggressive
      therapy, she died on the third day following admission to the intensive care unit
      due to secondary hypoxic-ischaemic encephalopathy. Blood and respiratory aspirate
      cultures showed community-acquired methicillin-resistant S. aureus (CA-MRSA) with
      a normal antibiotic sensitivity except for betalactam antibiotics. PCR-based
      methods demonstrated that the isolate possessed the Panton-Valentine-leukocidin
      (PVL) gene, encoding an S. aureus exotoxin that is associated with fulminant
      necrotising pneumonia. This case shows that clinicians in the Netherlands should
      also be aware of the possibility of CA-MRSA in patients without risk factors for
      MRSA carriage. Especially in children and adolescents with an influenza virus
      infection, pneumonia due to PVL-positive S. aureus strains may be life
      threatening.

PMID- 12814022
TI  - [Two hospital staff with throat carriage of methicillin-resistant Staphylococcus
      aureus, which had to be treated with systemic antibiotics].
AB  - Two hospital staff, women aged 20 and 22 years, were inadvertently found to be
      positive for methicillin-resistant Staphylococcus aureus (MRSA). Both had been in
      a hospital outside of the Netherlands, but due to the long period of time that
      had elapsed since then, they did not fall under the standard protocol for MRSA
      screening. After the usual wash procedure with chlorhexidine and mupirocin nasal
      ointment treatment, they remained positive for MRSA in the throat culture. Both
      patients still had their pharyngeal tonsils and were suffering from throat
      complaints. After systemic treatment with two antibiotics, they both became MRSA
      free. Throat carriership of MRSA might be a reason why MRSA eradication fails in
      the case of apparently healthy healthcare workers. The addition of a throat
      culture to the screening of healthcare workers would therefore be useful.

PMID- 12814023
TI  - [Fever, large eyes and confusion; the anticholinergic syndrome].

PMID- 12814024
TI  - [Fever, large eyes and confusion; the anticholinergic syndrome].

PMID- 12814025
TI  - [Fever, large eyes and confusion; the anticholinergic syndrome].

PMID- 12814026
TI  - [Fever, large eyes and confusion; the anticholinergic syndrome].

PMID- 12814027
TI  - [Diagnostic image (128). A boy who refused to walk. Spondylodiscitis LIV-LV].

PMID- 12814028
TI  - [Outbreaks of viral gastroenteritis, in particular due to the Norwalk virus: an
      underestimated problem].

PMID- 12814029
TI  - [Conservative treatment of a spontaneous splenic rupture in a patient with
      infectious mononucleosis].

PMID- 12814030
TI  - Herbal medicine in COPD: tradition or revolution?

PMID- 12814031
TI  - What is new in the air?

PMID- 12814032
TI  - Pertussis in the aetiology of chronic cough in adults.

PMID- 12814033
TI  - GENEBU Project. Equipment and drugs used for home nebulizer therapy in Italy.
AB  - The GENEBU Project is an open, observational survey evaluating home nebulizer
      practices in Italy. It consecutively included patients who were referred to one
      of the 27 participating chest clinics from May to December 1999 and who had been
      using a home nebulizer in the previous six months. The information source was a
      self-administered questionnaire compiled by the enrolled subjects. We collected
      1257 questionnaires. The nebulizer equipment was heterogeneous, with at least 92
      different models. Jet nebulizers were 90% of the total; 53% of these had a glass
      reservoir. Almost 80% of the patients selected the nebulizer themselves without
      any medical advice. In addition, most patients (> 80%) did not receive
      information on both the interface system and the optimal fill volume of the
      nebulizer. Corticosteroid nebulisation was widespread (74%), for both occasional
      and regular daily use, for both acute and chronic diseases from upper to lower
      airways. Beta 2-agonist (55%), anticholinergic (37%), mucolytic (32%) drugs were
      also often nebulised. More than 90% of patients mixed some active drugs. We
      conclude that the nebulizer equipment for home aerosol therapy was very
      heterogeneous and, probably, not always utilised at its best in Italy. The mixing
      of drugs and the widespread use of corticosteroids were peculiarities of home
      nebulizer therapy in Italy.

PMID- 12814034
TI  - The effect of age on cell-mediated immunity to tuberculin: a study on in vivo and
      in vitro tuberculin reactivity.
AB  - We investigated reactivity to tuberculin in a group of 91 elderly subjects (65
      years old and more) and in a control group of 53 younger subjects between 18 and
      59 years old, by means of the tuberculin skin test (TST) and by an in vitro
      lymphocyte stimulation test (LST). The LST had been validated in preliminary
      tests to accurately reflect T cell reactivity towards tuberculin. We defined a
      LST with a stimulation index (SI) (ratio of the tuberculin stimulated cultures to
      the non-stimulated cultures) of 10 or more at a concentration of 0.4 microgram/ml
      as indicative for sensitisation to tuberculin. The correlation between TST and
      LST was r = 0.58 (p = 0.0001) in the elderly subjects and r = 0.64 (p = 0.0001)
      in the younger age group; age did not affect those correlations (p = 0.39). Of
      the subjects with initially negative TST, 44.4% (16 LST-positive and 16 LST
      negative) reacted positive on TST as well as on LST after repeated testing. We
      conclude that (a) there is a statistically significant but rather weak
      correlation between in vivo and in vitro assays of cell-mediated immune response
      to tuberculin, (b) age did not influence this correlation, (c) the in vivo and in
      vitro tests give complementary information but cannot substitute for each other
      and (d) repeated TST can induce an immunological boosting phenomenon on TST as
      well as on LST.

PMID- 12814035
TI  - Ginseng improves pulmonary functions and exercise capacity in patients with COPD.
AB  - Ginseng is a root that has been used to treat patients with various illnesses for
      the last 2000 years. The purpose of this study was to evaluate the effects of
      Ginseng extract (G115) on Pulmonary Function Tests (PFTs), Maximum Voluntary
      Ventilation (MVV), Maximum Inspiratory Pressure (MIP) and Maximal Oxygen
      Consumption (VO2max) in patients with moderately-severe Chronic Obstructive
      Pulmonary Disease (COPD). Ninety-two adults were randomly divided into the
      experimental (n = 49, G115 100 mg bid for three months) and placebo-control (n =
      43) groups. PFTs, MVV and MIP were studied before treatment and every two weeks
      for the 3-month-study period. Exercise test and VO2max measurements were
      performed before the beginning and after six weeks and three months. P lower than
      0.05 was considered significant. Baseline demographics and pulmonary parameters
      were similar between the groups. In the experimental, but not in the control
      group, all parameters significantly increased above baseline and compared with
      the placebo group. Maximum increase, compared with baseline was FVC-32.5%, FEV1.0
      27.0%, PEF-27.5%, FEF50-45.4%, FEF75-56.9%, MVV-40.4%, MIP-47.0% and VO2max
      37.5%. No side effects were observed. G115 100 mg bid for three months, but not
      placebo, improved PFTs, MVV, MIP and VO2 max in patients with moderately-severe
      COPD with no side effects.

PMID- 12814036
TI  - Pertussis in adults. A study in an Italian population with chronic cough.
AB  - OBJECTIVE: Pertussis is commonly regarded as a disease of children but a number
      of clinical studies show that quite often it occurs in older children and adults,
      too. The purpose of the present study was to determine the prevalence of
      Bordetella pertussis infection in an Italian population of adults with persistent
      non-productive cough. METHODS: Pertussis was considered in the differential
      diagnosis of a prospective case series of 180 adult patients with unexplained non
      productive chronic cough. To diagnose pertussis, nasopharyngeal swabs for culture
      were obtained and antibodies IgA and IgG against multiple B. pertussis whole body
      antigens were counted by enzyme-linked immunosorbent assay in a single serum
      sample. RESULTS: The prevalence of pertussis with unexplained persistent cough
      was 10% of the cases. Significantly high amounts of specific IgA, that is at
      least 2 standard deviations greater than the geometric mean of the control group,
      were observed in 19 subjects. None of these patients had the typical symptoms of
      pertussis. CONCLUSIONS: Pertussis is quite a common cause of persistent cough in
      adults and should always be considered in differential diagnosis. Pertussis cases
      can easily be diagnosed by demonstrating IgA antibodies high titers in single
      serum samples, compared with those of population controls.

PMID- 12814037
TI  - Death certificates in asthma and COPD patients (survey of statistical data in
      Warsaw).
AB  - Mortality statistics regarding asthma and COPD (in the older age groups) are
      probably lower due to the misplacement of underlying and additional causes of
      death in the death certificates. To check this possibility, all death
      certificates over one year were reviewed(20.881) in Warsaw. In 1,431 cases
      (6.85%) the medical diagnoses were missing. Asthma, COPD and Pulmonary Heart
      Disease (PHD) (excluding any other cause of PHD) were mentioned at some point in
      315 cases (on one of the three items cards). 212 deaths occurred in hospital, 103
      at home (22 were regarded as sudden deaths). After reviewing records from 16
      hospitals and patients' local clinics, the existence of long-standing asthma
      and/or COPD was confirmed in all cases. Considering all the three items
      (underlying, secondary, direct causes) in the death certificates the mortality
      rates (for 100,000 all-age inhabitants) were established for asthma--4.51 for
      COPD--10.54, for PHD--3.23 (different from official statistics). PRINCIPAL
      CONCLUSIONS: The main sources of underestimation in mortality from asthma and/or
      COPD (in official statistics) are: 1) disregarding the "additional" and
      "immediate" causes of death, 2) regarding PHD as an underlying cause of death, 3)
      the lack of medical diagnoses in great number of death certificates.

PMID- 12814038
TI  - Exhaled biomarkers in COPD: their potential role in diagnosis, treatment and
      prognosis.
AB  - Several diagnostic tools have been developed for diagnosing, monitoring and
      evaluating Chronic Obstructive Pulmonary Disease (COPD). There is an increasing
      interest in the use of non or less invasive biological markers (biomarkers) which
      reflect the character and intensity of the pathological processes in the lungs of
      COPD patients. The main goal of this review was to discuss the origin and current
      role of exhaled biomarkers in the diagnosis, evaluation of treatment and
      prognosis of COPD. Data of cross-sectional, cohort and intervention studies on
      exhaled biomarkers were studied. These studies were identified by a Medline
      search on papers in the English language published from 1990 to November 2001.
      The following markers were discussed: exhaled nitric oxide (NO), exhaled carbon
      monoxide (CO), exhaled alkanes, exhaled hydrogen peroxide (H2O2), exhaled
      isoprostanes, exhaled NO metabolites and exhaled thiobarbituric acid-reactive
      substances (TBARs). Data on these markers were summarized. The origin of each
      marker, the technique of analysis, the values in healthy controls and COPD
      patients, the effect of treatment and the correlation with other parameters were
      presented. Most studies, however, were cross-sectional studies with small
      populations. It was also difficult to compare studies because of differences in
      technique and study population. This review shows that exhaled biomarkers need to
      be studied further before using them in clinical practice. There is a need for
      standardization of the measurements, for comparison of COPD patients with healthy
      persons matched for age and smoking-status, for data on reproducibility and
      variability of all markers, for correlation of exhaled markers with other
      parameters and for intervention studies.

PMID- 12814039
TI  - Non invasive mechanical ventilation in cystic fibrosis: physiological effects and
      monitoring.
AB  - Chronic respiratory insufficiency in cystic fibrosis (CF) is characterised by an
      increase in respiratory load, which leads to alveolar hypoventilation with the
      preservation of respiratory muscle strength. Non-invasive mechanical ventilation
      (NIMV) is able to improve alveolar ventilation and thus gas exchange and allow
      the the respiratory muscles to rest in patients with cystic fibrosis with
      variable severity of lung disease. These effects state the superiority of NIMV
      compared to oxygen therapy in CF. Invasive, highly specialized monitoring is
      recommended for the evaluation of ventilatory modes and the performances of new
      ventilators. After a successful evaluation, the monitoring of patients starting
      NIMV can be performed with simple, non invasive parameters such as gas exchange,
      tidal volume, respiratory rate, minute ventilation and comfort. In the long term
      however, studies are warranted to assess the benefit of NIMV in terms of lung
      function, quality of sleep and most importantly, quality of life.

PMID- 12814040
TI  - Nocturnal ventilation in neuromuscular disease--when and how?
AB  - While much evidence has been gained over the last decade to support the use of
      non-invasive ventilation (NIV) in a series of acute and chronic applications,
      some issues still need to be addressed, particularly regarding the timing of
      initiation of NIV and the best methods of implementation. This article discusses
      the role of NIV, if any, in preventing respiratory decline, as a physiotherapy
      adjunct, and in perioperative care for adults and children with neuromuscular
      disease.

PMID- 12814041
TI  - Impact of sleep on respiratory muscle function.
AB  - Sleep has well recognised effects on respiratory muscle function, most of which
      are detrimental. Upper airway dilator muscle function is compromised, which
      predisposes to obstruction, particularly during rapid-eye-movement sleep (REM).
      The diaphragm and accessory muscles of respiration are differently affected by
      sleep. Diaphragmatic function is largely preserved, which is essential for the
      maintenance of adequate ventilation during sleep. However, accessory muscle
      function is reduced, particularly during REM sleep, which may have adverse
      effects on lung mechanics. These changes contribute to hypoventilation and
      worsening ventilation-perfusion mismatching, particularly in patients with
      chronic lung disease such as COPD, with resulting oxygen desaturation.

PMID- 12814042
TI  - Smoking reduction in the management of COPD.

PMID- 12814043
TI  - Problems to control TB in eastern Europe and consequences in low incidence
      countries.
AB  - The regular decline in tuberculosis (TB) notification rates observed in the
      majority of industrialised countries over the past decades has levelled off or
      reversed in recent years in both the USA and in Europe, where relevant
      differences between Central/Eastern and Western countries have become more and
      more apparent. In the countries of the Central and Eastern European sub-region,
      notification rates have ceased to decline or markedly increased since the 1990s,
      particularly in the Baltic States, in Romania, Russian Federation and other
      countries belonging to the previous USSR. The evaluation of age-specific
      notification rates shows that the majority of the countries in the Central and
      Eastern European sub-region still have a pattern of middle-income countries,
      where TB is affecting significantly the younger cohorts, and the infection in the
      community is still rampant. The aim of the present paper is to discuss the main
      determinants of the deteriorated TB control in Eastern Europe, the main
      consequences of this situation for Western European Countries, and the possible
      solutions. The major constraints described are: socio-economic crisis, health
      system weaknesses, HIV pandemic, multidrug-resistant TB (MDRTB) and failure to
      control TB in prisons and in other risk groups. The main consequences of the sub
      optimal TB control achieved in Eastern Europe, are the exportation of TB trough
      immigration and, as part of this phenomenon, the exportation of drug resistance
      and MDRTB. Proper TB control is possible in the sub-region, as testified by the
      successful results achieved in the Czech republic, Slovakia and Slovenia. A
      global reform of health systems is necessary, particularly in the previous USSR
      countries, based on cost-effective interventions. MDRTB should be managed
      promptly as an international emergency, based on a cooperative approach of donor
      and assisted countries. As opportunities for improved funding of TB control in
      the region exist, there is the potential to reverse to TB pandemic before the
      explosion of the HIV epidemic expected in Eastern Europe.

PMID- 12814044
TI  - Low dose spiral computed tomography.
AB  - Low dose spiral computed tomography is the best tool we have today to detect
      early lung cancer. The author describes the technique of image intake and the
      advantages in thoracic oncology.

PMID- 12814045
TI  - Acute exacerbations of COPD: is inflammation central to prevention and treatment
      strategies?
AB  - Acute exacerbations (AE) represent one of the hallmarks of Chronic Obstructive
      Pulmonary Disease (COPD). They are characterised by increased from baseline
      dyspnoea, cough and sputum production and/or purulence, variably associated with
      fever and systemic symptoms. As in stable COPD, airway inflammation is an
      important part of the disease underlying the clinical manifestations. Studies on
      airway inflammation in AE by means of invasive methodologies (e.g. fiberoptic
      bronchoscopy with bronchial biopsy and/or bronchoalveolar lavage) are difficult
      due to clinical, practical and ethical issues. New and less- (sputum) or non
      invasive methodologies (exhaled markers) are becoming increasingly applied also
      to the study of AE in COPD. The overall data on airway inflammation during AE
      seems to indicate an "acute on chronic" picture of inflammation, with increased
      proportions of inflammatory cells in tissue and lavage/sputum samples and with
      the change in the proportions of some of the cell types, such as a substantial
      increase in the numbers of eosinophils. Cytokines and inflammatory mediators
      involved in AE seem to be those related to PMN chemotaxis (IL-8 and LT) and those
      related to eosinophilic inflammation. A more precise categorisation of the event
      causing AE (e.g. viral vs. bacterial), and of the baseline patients'
      characteristics (e.g. severe vs. mild-moderate stage) associated with a wider
      application of well-standardised non-invasive methodologies could bring us in the
      future better clues on the pattern of airway inflammation during AE.

PMID- 12814046
TI  - Evaluation of tuberculosis treatment results in Italy, report 1999.
AB  - In Italy no national data on tuberculosis (TB) treatment results was available.
      In 1995 the A.I.P.O. (Italian Association of Hospital Pneumologists) TB Study
      Group, in collaboration with the Istituto Superiore di Sanita (technical branch
      of the Ministry of Health) started a prospective monitoring activity based on the
      World Health Organisation and the International Union Against Tuberculosis and
      Lung Disease recommendations. Data was collected from a representative network of
      TB units nation-wide, managing a significant proportion of all TB cases notified
      in Italy each year. Aim of this study was to analyse the case-finding and
      treatment results for 1999. 906 TB cases were reported (61.2% males; 36.2%
      immigrants), 714 (78.8%) being new cases. Of these cases 639 (70.5%) were
      pulmonary, 221 (24.4%) extrapulmonary cases and 46 (5.1%) both pulmonary and
      extrapulmonary. The main risk-factors for TB were history of recent contact,
      diabetes and alcohol abuse among native Italians, the human immunodeficiency
      virus-seropositive status and history of recent contact among immigrants. The
      majority of immigrants came from Africa and Asia, and had stayed in Italy for
      more than 24 months before diagnosis of TB. Thirty-five per cent (320/906) of
      pulmonary patients had a positive direct sputum smear examination for alcohol
      acid-fast bacilli; 22.5% were resistant to any drug (from combined monoresistance
      to rifampicin: 1.6%; combined multi-drug resistance: 4.8%). In 97% of cases the
      duration of treatment was < 12 months. The overall success rate (cured plus
      treatment completed excluding transferred out from the denominator) was 86%. A
      significantly higher percentage of deaths were recorded amongst native Italians
      (being age-related; p < 0.001) while immigrants had a higher default rate (p <
      0.001).

PMID- 12814047
TI  - TB control strategies. Present and future in diagnostic methods: what the
      clinician can ask to the lab.

PMID- 12814048
TI  - Eosinophilic pleuropericarditis and fasciitis. A new case.
AB  - The case of a 29 year old male, non-smoker, with moderate dyspnea and
      subcutaneous limb swelling was reported. The final diagnosis of eosinophilic
      pleuropericarditis and fasciitis based on the presence of pleuropericardial
      effusion, painful arthromuscular swelling and peripheral eosinophilia. The
      particular involvement of forearms and calves furthermore differentiate the
      eosinophilic fasciitis from other arthromyalgic and neuromuscular syndromes.

PMID- 12814049
TI  - Massive unilateral hydrothorax as the only clinical manifestation of ovarian
      hyperstimulation syndrome.
AB  - We describe the case of a 36 old woman with a right massive hydrothorax resulting
      from Controlled Ovarian Hyperstimulation (COH) for infertility. This complication
      is defined as Ovarian Hyperstimulation Syndrome (OHSS) which usually includes
      abdominal pain, nausea and ascites, rarely involving the respiratory apparatus.
      The usual determining factors of OHSS are the presence of high serum estradiol
      levels and pregnancy. In the case that we describe the serum estradiol levels
      during COH were monitored and were slightly higher than the COH alarm threshold
      and the patient was not pregnant.

PMID- 12814050
TI  - Pulmonary blastoma: case report in an adult.
AB  - We present a case of biphasic pulmonary blastoma, a rare primary malignant lung
      neoplasm, in a 48 year old man. Despite its resection followed by postoperative
      chemotherapy, the neoplasm recurred and the patient survived only 41 months after
      the diagnosis.

PMID- 12814051
TI  - Severe complications following intravesical BCG instillation.
AB  - In patients with urinary bladder carcinoma, the intravesical BCG instillation is
      widely used. We present two cases of severe pulmonary afflictions developed
      during this treatment. The possible mechanisms of etiology are discussed and the
      classification of the intravesical BCG treatment side effects is suggested.

PMID- 12814052
TI  - The effect of transcutaneous electrical nerve stimulation on spasticity in
      multiple sclerosis patients: a pilot study.
AB  - The aim of this study was to examine the effects of transcutaneous electrical
      nerve stimulation on spasticity in patients with multiple sclerosis. The study
      was carried out in the Hacettepe University School of Physical Therapy and
      Rehabilitation. The subjects in the study were 10 clinically definite, primary
      and secondary progressive type multiple sclerosis outpatients with mild to
      moderate spasticity in the plantar flexor muscles of the ankle. Stimuli of
      frequency 100 Hz and pulse width 0.3 msec were used 20 minutes per day for 4
      weeks. Patients were assessed by electromyography, Modified Ashworth Scale, and
      Ambulation Index. Electromyography was performed before and after the daily
      treatment of spastic muscles with transcutaneous electrical nerve stimulation in
      order to assess the effect on muscle relaxation. The Modified Ashworth Scale and
      Ambulation Index were used before and after 4 weeks' treatment. After 4 weeks of
      treatment, there were statistically significant reductions in spasticity of both
      extremities as assessed by myoelectric activity and the Modified Ashworth Scale
      (P < 0.05). Ambulation Index level was not improved significantly (P > 0.05).

PMID- 12814053
TI  - Assessing mobility and locomotor coordination after stroke with the rise-to-walk
      task.
AB  - INTRODUCTION: To assess mobility and locomotor coordination after stroke with the
      rise-to-walk task (RTW) and to examine the construct and concurrent validity of
      this task. METHODS: Nineteen subjects who had sustained a stroke and 19 healthy
      subjects performed the RTW task. The performance was recorded simultaneously with
      2 clinical methods and 1 instrumented method. The RTW duration and fluidity of
      the motor strategy (fluid or nonfluid) were compared between groups and between
      methods. The relationship between RTW duration and 3 locomotor-related disability
      tests, as well as 1 motor impairment test, was studied. RESULTS: The subjects
      with stroke took 65% more time to complete the RTW task, and 16/19 separated the
      tasks of rising and walking (nonfluid strategy). Measures of the RTW duration
      with clinical methods were strongly correlated (r = 0.84 to 0.98) to those from
      the instrumented method, and the motor strategy was successfully assessed from
      video records. The duration was moderately correlated to scores from other
      locomotor-related tests, but not to the motor impairment test. DISCUSSION: The
      assessment of mobility and locomotor coordination with the RTW task indicate that
      both outcomes are impaired after stroke and that clinical methods provide a valid
      measurement of the task.

PMID- 12814054
TI  - Effects of practice and unpredictable distractors on planning and executing
      aiming after stroke.
AB  - The primary purpose of this study was to examine practice effects on the planning
      and execution of an aiming movement after right versus left stroke. A secondary
      purpose was to investigate the effects of a distractor that appeared randomly on
      motor performance after stroke. Right-hand dominant individuals, 15 with right
      stroke (right-sided brain damage), 16 with left stroke, and 30 without stroke,
      performed aiming movements to targets. Those with stroke used the ipsilesional
      upper extremity (UE). Right and left comparison groups used the right and left
      UE, respectively. Reaction time (RT) and movement time (MT) were collected to
      represent movement planning and execution, respectively. Individuals with right
      stroke improved RT with practice. Individuals with left stroke did not improve RT
      with practice and made more errors than their comparison group. Those with left
      stroke achieved faster MT with practice, but MT remained slower than their
      comparison group. There were no effects of the distractor on RT or MT. Adults
      with left stroke have persistent deficits in movement planning and execution.
      Further studies are needed to determine how the performance of older adults, with
      or without stroke, is affected by an unpredictable visual distractor.

PMID- 12814055
TI  - Effects of low-frequency cranial electrostimulation on the rest-activity rhythm
      and salivary cortisol in Alzheimer's disease.
AB  - OBJECTIVE: In previous studies, cranial electrostimulation (CES) had positive
      effects on sleep in depressed patients and in patients with vascular dementia.
      The present study examined the effects of low-frequency CES on the rest-activity
      rhythm and cortisol levels of patients with probable Alzheimer's disease (AD).
      METHOD: It was hypothesised that a decreased level of cortisol would parallel a
      positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD
      patients were randomly assigned to an experimental group (n = 8) or a control
      group (n = 8). The experimental group was treated with CES, whereas the control
      group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest
      activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in
      the saliva throughout the day by means of salivette tubes. RESULTS: Low-frequency
      CES did not improve the rest-activity rhythm in AD patients. Moreover, both
      groups showed an increase instead of a decrease in the level of cortisol.
      CONCLUSIONS: These preliminary results suggest that low-frequency CES has no
      positive effect on the rest-activity rhythm in AD patients. An alternative
      research design with high-frequency CES in AD is discussed.

PMID- 12814056
TI  - Intramuscular hand neuroprosthesis for chronic stroke survivors.
AB  - The purpose of this study was to assess the feasibility of a percutaneous hand
      neuroprosthesis system for stroke survivors. Case reports of 4 chronic stroke
      survivors who were implanted with percutaneous intramuscular electrodes in
      various muscles of the forearm for hand grasp and release are presented. A
      percutaneous hand neuroprosthesis was able to open a spastic hemiparetic hand as
      long as the upper limb was in a resting position, the wrist and proximal forearm
      were supported, participants did not try to assist the stimulation, and an
      individual other than the participant modulated the stimulation. However, when
      participants tried to assist the stimulation or complete a functional task, hand
      opening was significantly reduced due to increased finger flexor hypertonia, even
      with increased stimulation intensity. Similarly, electrically stimulated hand
      opening was significantly reduced following voluntary hand closure. Techniques
      that provide real-time modulation of hypertonia with closed loop control, control
      strategies that are independent of the contralateral limb, and methods to enhance
      proximal control must be developed to demonstrate the feasibility of a hand
      neuroprosthesis system for persons with hemiparesis.

PMID- 12814057
TI  - The impact of ulnar nerve compression at the elbow on the hand function of heavy
      manual workers.
AB  - The objectives of this article were to study the impact of the hand function
      disability due to ulnar neuropathy at the elbow (UNE) on workers engaged in
      occupations requiring heavy hand use. Four patients (42.5 +/- 7 years old), all
      engaged in heavy-duty jobs, with severe conduction block but without severe
      axonal loss were recruited. The severity of ulnar nerve compression was
      quantified based on electrophysiologic studies, Jebsen-Taylor Hand Function Test,
      Jamar dynamometer, and Semmes-Weinstein Monofilaments Test. UNE resulted in a
      reduction in hand strength without any significant impact on fine motor
      dexterity. The 4 laborers whose work required strong hand grip found this
      debilitating. Severe UNE affects the hand function of heavy manual workers by
      impeding their grip and pinch strengths. However, UNE does not affect tasks
      requiring fine hand dexterity.

PMID- 12814058
TI  - [Cellular and molecular mechanisms of sodium pump activation in experimental
      models of nephrotic syndrome].
AB  - Edema represent an abnormal expansion of the intersTitial compartment which
      belong to the extracellular volume. This interstitial expansion is linked to the
      accumulation of sodium in the extracellular volume due to an imbalance between
      sodium intake and urinary sodium output. The stimulation of tubular sodium
      reabsorption is located in the collecting duct where a stimulation of sodium pump
      hydrolytic activity has been evidenced. The excess of sodium pump hydrolytic
      activity is associated with an overexpression of the alpha subunit of the sodium
      pump at the cell surface and a transcriptional induction of alpha and beta sub
      units mRNAs. This overexpression is synchronized with the decrease of the final
      urinary sodium excretion, the positivation of sodium balance and the period of
      ascites formation.

PMID- 12814059
TI  - [Hemodialysis-related pruritus. A study of 134 Moroccans ].
AB  - The prevalence of pruritus varies from 60% to 90% in patients receiving
      hemodialysis. The aim to this study was to evaluate the frequency of pruritus and
      its characteristics among moroccan patients receiving hemodialysis. Pruritus
      related to primary skin disease or other identified cause than chronic renal
      failure was excluded. Biological parameters were compared between patients with
      pruritus and those without. Pruritus occurred in 74.4% of hemodialysis patients
      and concerned 66 men and 68 women, mean age 44.8 + 14 years. Duration of
      hemodialysis varied between 5 months to 10 years. Main characteristics of
      pruritus were a general pattern in 70%, moderate intensity in 50%, appearance
      after dialysis in 81.2% and severe psychologic repercussion in 20.8%.
      Antihistamines first-line treatment was rarely effective. UVB radiation used in 7
      cases leaded to a marked improvement. This study underlined the high frequency of
      pruritus in moroccan patients with chronic renal failure on maintenance
      hemodialysis. Hemodialysis can initiate this symptom as well as improve it.
      Biological parameters were not different between patients with or without
      pruritus. It also pointed out on therapeutic challenges. However, UVB radiation
      seems to be an effective therapy in intractable itching as well as increased
      frequency of weekly courses of hemodialysis. Long term skin hydratation should be
      also highly recommended.

PMID- 12814060
TI  - [Hepatitis C infection among patients receiving hemodialysis].
AB  - In France, the prevalence of hepatitis C virus (HCV) infection in chronic
      hemodialysis patients is high, about 15 to 42%. Although the incidence and the
      prevalence of HCV infection decreased during the last decade, de novo cases of
      HCV infection still occur in hemodialysis units. To date the nosocomial
      transmission is the principal cause of contamination. The strict application of
      universal precautions and the separation of chronic hemodialysis patients
      according to their virological status may decrease the incidence of HCV infection
      in hemodialysis units. The transaminase level and HCV viremia are lower in
      chronic hemodialysis patients than that in the general population. Liver disease
      seems also to be less aggressive. Chronic hemodialysis patients presenting acute
      hepatitis C infection and those waiting for renal transplantation have to be
      treated by interferon-alpha (IFN-alpha), since the virological response is
      elevated and sustained. In case of cirrhosis or severe liver disease, a combined
      liver-kidney transplantation can be proposed after IFN-alpha therapy. Finally, in
      chronic hemodialysis who are not candidate for renal transplantation IFN-alpha
      therapy can be discussed according the patients' age and general health status.

PMID- 12814062
TI  - The ultimate trust.

PMID- 12814063
TI  - Urgent: upgrading health alert systems.

PMID- 12814061
TI  - [Cardiovascular calcifications in hemodialysis patients. Prevalence and risk
      factors].
AB  - OBJECTIVES: Cardiovascular diseases are the leading cause of morbidity and
      mortality in chronic hemodialysed patients. The aim of our study was to determine
      the prevalence of cardiovascular calcifications in dialysed patients and to
      evaluate their risk factors. METHODS: We did a transversal study in 86
      chronically hemodialysed patients in the hemodialysis department, Ibn Sina
      university hospital (Rabat). All patients, 44 men and 42 females, mean age 42 +/-
      15.5 years were hemodialysed for more than one year. FINDINGS: The prevalence of
      cardiovascular calcifications was 24.5%. Chronic hemodialysed patients with
      cardiovascular calcifications were older (50.5 years +/- 15.4 vs 39 years +/-
      14.6; p = 0.003). They had a long hemodialysis duration (81 months +/- 51 vs 59
      months +/- 43; p = 0.05) and a higher calcium plasmatic concentration (2.27 +/-
      0.15 vs 2.1 +/- 0.19 mmol/l; p = 0.03). We noted a male gender predominance (sex
      ratio M/W = 18/3 vs 26/39; p = 0.0002). Multivariate analysis showed, as an
      independent predictor of cardiovascular calcifications, the old age (p = 0.01).
      Cardiovascular calcifications seem uncommon in our hemodialysis patients. Older
      age, longer hemodialysis duration and male gender are risk factors. The use of
      low doses of calcium carbonate, vitamin D and low milk products diet may explain
      this low prevalence.

PMID- 12814064
TI  - Loss prevention case of the month. What is going on here?

PMID- 12814065
TI  - Here to help: an interview with Jack R. Woodside, Jr., MD. Physicians Health
      Program Assistant Medical Director.

PMID- 12814067
TI  - Community acquired pneumonia--how does Tennessee measure up?

PMID- 12814066
TI  - Intercostal artery aneurysm complicating aortic coarctation in a 71-year-old
      woman.
AB  - We present a case of aortic coarctation associated with many intercostal artery
      aneurysms in a 71-year-old woman. The intercostal aneurysm appeared,
      radiographically, as a very well demarcated lung mass with hilar enlargement
      giving the false idea of lung tumor and adenopathy. The case illustrates the
      importance of keeping such a diagnosis in mind in patients presenting with an
      abnormal chest x-ray. To our knowledge this is the first case report of aortic
      coarctation complicated by intercostal aneurysm at this age group.

PMID- 12814068
TI  - The uncivil war against health care fraud. Who will be excluded next? Part II.

PMID- 12814069
TI  - Special supplemental nutrition program for women, infants, and children (WIC).

PMID- 12814070
TI  - Scanning for a stronger association. Environmental assessment efforts.

PMID- 12814071
TI  - What counts. Facts, figures, findings.

PMID- 12814073
TI  - Avoiding manager paralysis. A case for annual benchmarking.

PMID- 12814074
TI  - Vendor HIPAA readiness critical to ensure payment.

PMID- 12814075
TI  - Hack attack. Take steps to keep your system secure.

PMID- 12814076
TI  - The (anti-)sludge report. Use change as a strategy for creative medical
      leadership.

PMID- 12814077
TI  - Nobody does it better. Physicians excel at single-specialty disease management.

PMID- 12814078
TI  - Don't let tangled lines snarl your response. Communications critical in
      emergencies.

PMID- 12814079
TI  - Leading the way to success. Create trust, teamwork to make your practice shine.

PMID- 12814080
TI  - It's there if you look. Get value out of technology to improve operations.
AB  - Is your group missing out on practice-management system functions critical to
      efficient operations and reduced overhead? Most practices don't maximize the
      capabilities of their office systems, hampering operational efficiency.

PMID- 12814081
TI  - On your mark. Benchmark reporting is key to practice improvement.
AB  - A best-practices benchmark process is a powerful tool to accomplish improvement
      goals. This article presents an operational benchmark analysis and action plan to
      help you set performance parameters in your organization.

PMID- 12814082
TI  - Looking askance. Do you need to audit your payments?
AB  - Know the warning signs that indicate your practice is losing money through
      underpayments. A constellation of factors combine to conceal financial drainage
      from third-party payers--but the alert administrator can spot and reverse the
      problem.

PMID- 12814083
TI  - Begone with you. Dismissing problem patients from your practice.
AB  - Every group practice administrator eventually deals with the question of whether
      and how to dismiss a problem patient from the practice. A written policy can help
      ensure that each situation is handled appropriately, with strict adherence to
      medical, legal and ethical guidelines.

PMID- 12814084
TI  - Nursing education: addressing the nursing shortage.

PMID- 12814085
TI  - Creative responses to the nursing shortage.

PMID- 12814086
TI  - The value of mentoring for multi-cultural students.

PMID- 12814087
TI  - Smallpox vaccination program update: April 2003.

PMID- 12814088
TI  - [Reports from the American Thoracic Society Annual Congress. Atlanta, Georgia,
      USA. 17-22 May 2002].

PMID- 12814090
TI  - Getting children to try new foods.

PMID- 12814089
TI  - Lead levels in children: how low must they go?

PMID- 12814091
TI  - New guidelines for preventing rickets.

PMID- 12814092
TI  - Flushing wounds in children--is tap water OK?

PMID- 12814093
TI  - Selecting appropriate toys for children.

PMID- 12814094
TI  - What's the big deal about handwashing? ...and here's something that can help.

PMID- 12814095
TI  - [Comparison of the chemical constituents and pharmacological action of Piper
      nigrum Linn. with P. methysticum forst].

PMID- 12814096
TI  - [Advances in the study of the chemical constituents and biological activities of
      3 species of Echinacea].

PMID- 12814097
TI  - Bibliography of journal articles (January to June 2002).

PMID- 12814099
TI  - Causal judgment as evaluation of evidence: the use of confirmation and
      disconfirmatory information.
AB  - There are four kinds of contingency information: occurrences and nonoccurrences
      of an effect in the presence and absence ofa cause. In two experiments
      participants made judgements about sets of stimulus materials in which one of
      these four kinds had zero frequency. The experiments tested two kinds of
      predictions derived from the evidential evaluation model of causal judgement,
      which postulates that causal judgement depends on the proportion of instances
      evaluated as confirmatory for the cause being judged. The model predicts
      significant effects of manipulating the frequency of one kind of contingency
      information in the absence of changes in the objective contingency. The model
      also predicts that extra weight will be given to one kind of confirmatory
      information when the other kind has zero frequency, and to one kind of
      disconfirmatory information when the other kind has zero frequency. Results
      supported both sets of predictions, and also disconfirmed predictions of the
      power probabilistic contrast theory of causal judgement. This research therefore
      favours an account of causal judgement in which contingency information is
      transformed into evidence, and judgement is based on the n et confirmatory or
      disconfirmatoryvalue of the evidence.

PMID- 12814098
TI  - Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and
      promoting apoptosis of neointimal smooth muscle cells.
AB  - In cultured vascular smooth muscle cells (SMCs), STAT3 mediates proliferation
      signal by directly activating transcription of early growth response genes.
      Recently, we have found that balloon injury transiently induces JAK2 and STAT3
      expressions and activations with a peak at day 7 in rat carotid artery. However,
      the specific role of STAT3 in neointima formation remains unknown. Adenoviral
      vector encoding a dominant negative STAT3 (AxCAdnSTAT3) or beta-galactosidase
      (control) was overexpressed in a balloon-injured artery to inhibit endogenous
      STAT3 activation selectively. In controls, neointima became evident after day 4,
      and reached a maximum at day 14. The number of bromodeoxyuridine (BrdU)-positive
      proliferating or TUNEL-positive apoptotic neointimal SMCs peaked at day 7,
      decreasing to lower levels by day 14. AxCAdnSTAT3 not only abrogated STAT3
      phosphorylation but also decreased BrdU labeling index by 60% and increased TUNEL
      index by 35% at day 7 versus controls, resulting in the 40% reduction in the
      intima/media area ratio at day 14. At day 7, in controls, vascular injury
      upregulated antiapoptotic mediator Mcl-i and Bcl-xL expression by 8-fold to 5
      fold, respectively, versus sham, whereas proapoptotic Bax slightly increased by
      1.5-fold versus sham. AxCAdnSTAT3 reversed the upregulated Mcl-1 and Bcl-xL
      levels by 70% and 37%,respectively, while having no affect on Bax expression. In
      conclusion, the STAT3-mediated pathway plays an important role in neointima
      formation through enhanced vascular SMC accumulation by promoting cell
      proliferation and survival.

PMID- 12814100
TI  - Pediatricians' knowledge, perceptions, and attitudes towards providing health
      care for lesbian, gay, and bisexual adolescents.
AB  - BACKGROUND: Pediatricians are often the first health-care contacts for gay,
      lesbian, and bisexual adolescents who are developing their sexual orientation.
      OBJECTIVE: This study investigated pediatricians' attitudes and practices towards
      gay, lesbian, and bisexual adolescents. METHOD: We sent anonymous self
      administered questionnaires to 112 pediatricians in the Ottawa area. RESULTS: Of
      those who responded, 36 per cent reported having treated lesbian, gay, or
      bisexual patients, and 70 per cent reported not addressing the issue of sexual
      orientation. Reservations in discussing sexual orientation were due to fears of
      offending patients, and a lack of knowledge regarding their needs. Furthermore,
      59 per cent of these pediatricians were unfamiliar with community resources for
      homosexual youths, and 78 per cent reported wanting more information with regards
      to the care of this population. CONCLUSION: Many pediatricians experience
      difficulties in discussing issues of sexual orientation, and generally feel
      inadequately prepared to address issues pertaining to the health-care needs of
      these adolescents. While certain issues remain controversial, the overall
      attitude of pediatricians towards homosexually oriented patients is positive in
      that they are interested in becoming more aware of issues of homosexual
      orientation, to better serve this population.

PMID- 12814101
TI  - Mapping of the human genome.

PMID- 12814102
TI  - Eugenics and the Human Genome Project.

PMID- 12814103
TI  - The writing is on the wall.

PMID- 12814104
TI  - The hazards of human developmental gene modification.

PMID- 12814105
TI  - Human germline engineering and cloning as women's issues.

PMID- 12814106
TI  - On order.

PMID- 12814107
TI  - Childbearing in the age of biotechnology.

PMID- 12814108
TI  - Progressive multifocal leukoencephalopathy:   cidofovir therapy in three patients
      with underlying hematological disease.

PMID- 12814110
TI  - Emergency contraception and stroke.

PMID- 12814109
TI  - Patents revealed on cloned mammals, including humans.

PMID- 12814112
TI  - Posterior CT guided approach for botulinum toxin injection into spinal psoas.

PMID- 12814111
TI  - Institutional conflicts of interest and research with human subjects.

PMID- 12814113
TI  - Embryos and research with human subjects.

PMID- 12814114
TI  - Inclusion body myositis in a patient with a presumed diagnosis of post-polio
      syndrome.

PMID- 12814115
TI  - [Life and works of Gabor Veza, the first protomedicus of Hungary].
AB  - Gabor Veza (1728-1799) was the first "protomedicus Hungariae" (head-physician of
      Hungary). The present paper, based mostly on recently discovered archival data
      reconstructs his biography and corrects some mistakes of the previous
      biographical works. Veza's curriculum vitae shortly sounds as follows: Born in
      Vienna, in 1728 in an Austrian, Catholic family. His father had been Josef Veza,
      an agent of the Habsburg emperor in the Low Countries. Gabor Veza graduated in
      Toscana in Pisa (1751) later practised medicine in military hospitals, practising
      privately too. During this period he moved to Buda. He repeated his graduation at
      the University of Vienna as well (1757) and stood in military service for 25
      years (till 1787) as a leading surgeon of the Garrison at Buda. At the same time
      he worked as a medical officer of County Pest. In 1777 he was appointed to
      director of medical faculty of the Royal Hungarian University, in 1787 to Royal
      Counsellor, in 1787 to Protomedicus of Hungary.

PMID- 12814116
TI  - Researcher sues institutional review board (IRB) members and university.

PMID- 12814117
TI  - Normal pressure hydrocephalus manifesting as an obsessive-compulsive disorder
      responding to CSF drainage.

PMID- 12814118
TI  - Multiphasic demyelinating disorder with acute transverse myelitis in Japanese.

PMID- 12814119
TI  - Hashimoto's encephalopathy presenting with musical hallucinosis.

PMID- 12814120
TI  - Diagnostic problems during late course in Creutzfeldt-Jakob disease.

PMID- 12814121
TI  - Increased monocyte tissue factor activity in women following cerebral venous
      thrombosis.

PMID- 12814122
TI  - Transient global amnesia and transient topographical amnesia: an observation
      favoring the hypothesis of a common pathogenesis.

PMID- 12814123
TI  - Odourant intensity and valance are processed by distinct human brain regions.

PMID- 12814124
TI  - Response to "Should clinicians incorporate positive spirituality into their
      practices? What does this evidence say?".

PMID- 12814125
TI  - Good publication practice for pharmaceutical companies.
AB  - Guidelines on Good Publication Practice (GPP) for pharmaceutical companies are
      presented. The aim of the guidelines is to ensure that clinical trials sponsored
      by pharmaceutical companies are published in a responsible and ethical manner.
      The guidelines cover companies' responsibility to an endeavour to publish results
      of all studies, companies' relations with investigators, measures to prevent
      redundant or premature publication, methods to improve trial identification and
      the role of professional medical writers. Our aim in publishing the GPP
      guidelines, which are the first to be developed by and for those working on
      publications in the pharmaceutical industry, is to stimulate discussion between
      journals, investigators and trial sponsors and to provide guidance to those who
      seek it. We also hope that pharmaceutical companies and others involved in
      developing publications arising from sponsored clinical trials will endorse the
      guidelines.

PMID- 12814126
TI  - Good publication practices for pharmaceutical companies: why we need another set
      of guidelines.

PMID- 12814127
TI  - Statin-fibrate combination: therapy for hyperlipidemia: a review.
AB  - Statins and fibrates are well-established treatments for hyperlipidaemias and the
      prevention of vascular events. However, fibrate + statin therapy has been
      restricted following early reports of rhabdomyolysis that mainly involved
      gemfibrozil, originally with bovastatin, and recently, with cerivastatin. Despite
      this limitation, several reports describing combination therapy have been
      published. This review considers these studies and the relevant indications and
      contraindications. Statin + fibrate therapy should be considered if monotherapy
      or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty
      acids ornicotinic acid) did not achieve lipid targets or is impractical.
      Combination therapy should be hospital-based and reserved for high-risk patients
      with a mixed hyperlipidaemia characterised by low density lipoprotein cholesterol
      (LDL) >2.6 mmol/l(100 mg/dl, high density lipoprotein cholesterol (HDL) <1.0
      mmol/l (40 mg/dl) and/or triglycerides> 5.6 mmol/l (500 mg/dl. These three
      'goals' are individually mentioned in guidelines. Patients should have normal
      renal, liver and thyroid function tests and should not be receiving therapy with
      cyclosporine, protease inhibitors or drugs metabolised through cytochrome P450
      (especially 3A4). Combination therapy is probably best conducted using drugs with
      short plasma half-lives; fibrates should be prescribed in the morning and statins
      at night to minimise peak dose interactions. Both drug classes should be
      progressively titated from low doses. Regular (3-monthly) monitoring of liver
      function and creatine kinase is required. In conclusion, fibrate + statin therapy
      remains an option in high-risk patents. However, long-term studies involving
      safety monitoring and vascular endpoints are required to demonstrate the efficacy
      of this regimen.

PMID- 12814128
TI  - Nicotinic receptors and Alzheimer's disease.
AB  - Nicotinic receptors (NRs) belong to the group of polymeric receptors of the cell
      membrane and are key elements of cholinergic transmission. Numerous subtypes of
      NRs exist with the alpha 4 beta 2 and alpha 7 types being encountered most
      frequently. Deficiencies in NRs seem to play a role in Alzheimer's disease, which
      is characterised by accumulation of senile plaques, mainly composed of beta
      amyloid peptide (beta A). Although the aetiology of this disease is unknown,
      different pathogenesis hypotheses implicating alpha 7 NRs have been proposed,
      with the receptors exerting a direct or indirect action on the mechanism of beta
      A toxicity. Allosteric modulators of NRs, such as the cholinesterase inhibitor
      galantamine, that facilitate the action of acetylcholine on these receptors may
      provide therapeutic benefits in the areas of cognition, attention and
      antineurodegenerative activity.

PMID- 12814129
TI  - Do positive psychological states shed light on recovery from bereavement?
      Findings from a 3-year longitudinal study.
AB  - The purpose of the current study was to document the course and 1-month post
      bereavement predictors of both positive and negative psychological states in
      bereaved gay male caregivers for 3 years following the death of their partners.
      The results show that although the patterns of post-bereavement depressive mood
      and positive psychological states were similar, some of their predictors
      differed. Given that the processes that produce positive psychological states are
      not the same as those that produce negative states, our findings support the
      inclusion of both positive and negative psychological states in studies of post
      bereavement adjustment.

PMID- 12814130
TI  - Physician-assisted suicide in Oregon: what are the key factors?
AB  - Oregon's Death with Dignity Act has been operative since late 1997. The
      substantial national and international interest in Oregon's law makes it
      important to document any possible trends in the characteristics of persons who
      use the law. To do this, the present article examines previously reported data
      from various sources and places them within the context of the end-of-life
      decisions more generally. The Oregon data demonstrate that, regardless of the
      care received, a very small percentage of terminally ill Oregonians seem
      determined to request a lethal medication so that they may control the manner and
      timing of their death. College graduates and divorced persons are substantially
      more likely to use physician-assisted suicide to end their lives than are other
      persons. Control and autonomy appear to be the primary issues associated with
      taking legally prescribed medication to hasten one's death. A better
      understanding of the influence that a patient's marital status, education level,
      and desire for control may have on her or his ability to cope with, and make
      decisions related to, a terminal illness may allow health care professionals to
      better care for dying patients.

PMID- 12814131
TI  - Meaning making in the aftermath of homicide.
AB  - Although sense making or finding benefit are well documented examples of meaning
      making processes, meaning making grounded in action has received less attention.
      This article adds a specific demonstration of the relevance of performed meanings
      to homicide survivors and other traumatized populations through a qualitative
      study of 38 members of 14 families. The central finding of the study points to
      "the intense pursuit of what matters" as a major avenue for meaning making in the
      aftermath of homicide, one which is expressed in action. Implications of this
      mode of meaning reconstruction are discussed relative to the re-establishment of
      a sense of coherence and self-continuity.

PMID- 12814132
TI  - Death obsession in Kuwaiti and American college students.
AB  - Two samples of Kuwaiti (n = 460) and American (n = 273) male and female
      undergraduates responded to the Death Obsession Scale (DOS) in Arabic and
      English, respectively. Cronbach's alpha reliability statistics were .96 and .91,
      respectively, denoting high internal consistency. In the same vein, all the item
      remainder correlations in both samples were significant denoting item validity
      and content validity. A general factor of death obsession was disclosed in the
      Kuwaiti sample, whereas two salient factors (death rumination, and death
      dominance and repetition) were extracted in the American sample. Gender-related
      differences were significant in the Kuwaiti sample, that is, females attained
      higher mean score than their male counterparts, whereas there were no significant
      gender differences in the American sample. Kuwaiti students attained
      significantly higher mean DOS score than their American counterparts in the total
      and all the individual items of the DOS.

PMID- 12814133
TI  - Boomers vs. X-ers.

PMID- 12814134
TI  - Boomers vs. X-ers.

PMID- 12814136
TI  - Applications for FDA approval to market a dew drug: patent submission and listing
      requirements and application of 30-month stays on approval of abbreviated new
      drug applications certifying that a patent claiming a drug is invalid or will not
      be infringed. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its patent submission and
      listing requirements for new drug applications (NDAs). The final rule clarifies
      the types of patents that must and must not be submitted and revises the
      declaration that NDA applicants must provide regarding their patents to help
      ensure that NDA applicants submit only appropriate patents. The final rule also
      revises the regulations regarding the effective date of approval for certain
      abbreviated new drug applications (ANDAs) and certain other new drug
      applications, known as 505(b)(2) applications, submitted under the Federal Food,
      Drug, and Cosmetic Act (the act). In certain situations, Federal law bars FDA
      from making the approval of certain ANDA and 505(b)(2) applications effective for
      30 months if the applicant has certified that the patent claiming a drug is
      invalid or will not be infringed, and the patent owner or NDA holder then brings
      suit for patent infringement. The final rule also states that there is only one
      opportunity for a 30-month stay in the approval date of each ANDA and 505(b)(2)
      application. The final rule will make the patent submission and listing process
      more efficient as well as enhance the ANDA and 505(b)(2) application approval
      processes.

PMID- 12814138
TI  - Sterility in home care.

PMID- 12814139
TI  - AIDS epidemic burgeoning in Asia and the Pacific. Various organizations issue
      warnings.

PMID- 12814140
TI  - Plants and gravity. Special issue.
AB  - This issue of the Journal of Plant Growth Regulation explores the effects of
      gravity on plant growth and development from several perspectives. Most of the
      review papers consider plants and gravity from the viewpoint of ground-based
      laboratory research, and several papers consider gravitropism, the directed
      growth in response to gravity, in some detail. However, another approach to study
      the effects of gravity on plant is to effectively remove the force due to
      gravity. A very dramatic way to accomplish this goal is through the free-fall
      conditions achieved by spacecraft in low Earth orbit, so some of the authors have
      reviewed recent advances in spaceflight research with plant systems.

PMID- 12814141
TI  - Reversibility to a beta2-agonist in COPD: relationship to atopy and neutrophil
      activation.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by limited
      bronchial reversibility and chronic neutrophilic inflammation. However, in some
      cases of COPD, eosinophilic inflammation is present. We investigated the
      relationship between reversibility to beta2-agonist with atopy and neutrophil
      activation in patients with stable COPD. For this purpose, 38 outpatients with
      COPD (mean age: 64 years) 12 with asthma (mean age: 51 years) and 13 healthy
      controls (mean age: 49 years) were tested using increasing doses of inhaled
      salbutamol (up to 3100 microg). According to their reversibility, COPD patients
      were divided into two groups: reversible COPD (deltaFEV1 > or = 12% pred, n = 16)
      and non-reversible COPD (deltaFEV1 < 12% pred, n = 22). Atopy, assessed by skin
      prick, was found at similar frequencies in both COPD groups. Total serum IgE was
      higher in COPD patients vs. controls, but did not differ significantly between
      the COPD groups. The blood eosinophil count was significantly higher in the
      reversible COPD group than in the non-reversible COPD, and correlated with
      deltaFEV % pred (Rs = 0.54, P < 0.05), as well as in asthmatics. The non
      reversible COPD group had a higher level of spontaneous neutrophil activation (by
      reduction of nitroblue tetrazolium) versus controls. We conclude that airway
      reversibility in COPD patients is associated with the degree of blood
      eosinophilia, but not with the degree of blood neutrophil activation.

PMID- 12814142
TI  - Long-term effects of almitrine bismesylate in COPD patients with chronic
      hypoxaemia.
AB  - BACKGROUND: Almitrine bismesylate (AB) is a peripheral chemoreceptor agonist
      which is believed to improve oxygenation of COPD patients with chronic
      hypoxaemia, probably by improving the ventilation perfusion mismatch. We studied
      the long-term effects of AB in COPD patients with chronic hypoxaemia. METHODS: 
      DESIGN: Prospective, randomised, double-blind, placebo-controlled trial. SETTING:
      Eight hundred bed teaching hospital with a catchment population of 350,000
      inhabitants. PATIENT RECRUITMENT: COPD outpatients consulting between September
      95 and September 99. INCLUSION CRITERIA: (1) COPD (FEV1 < 50%). (2) PaO2 < or =
      65 mmHg. (3) Stable arterial blood gases (ABG), spirometry (S) and clinical
      state. EXCLUSION CRITERIA: Asthma, restrictive disease, sleep apnoea syndrome,
      advanced renal or hepatic disease, peripheral neuropathy, use of respiratory
      stimulants or psychotrophic drugs. TREATMENT: AB 1 mg/kg/day (weight < 75 kg = 50
      mg/day; weight > or = 75 kg = 100 mg/day) in an intermittent schedule with
      resting periods of 1 month after the third, 6th and 9th months during 1 year.
      INSTRUMENTATION: Stabilisation period: S, ABG. Run-in period: S, ABG, 6-min
      walking test (WT), nocturnal pulse oximetry (NP) and quality of life evaluation
      (CRQ). Third, 6th and 9th months: S, ABG. End of the study: S, ABG, WT, NP, CRQ.
      STATISTICS: ANOVA for repeated measurements. RESULTS: Two hundred and eighty-nine
      patients were evaluated and 81 were included in the study. Sixty-six were
      followed for 6 months, 53 for 9 months and 42 for 1 year. Almitrine and placebo
      groups did not present significant differences in ABG and S in the 6th, 9th and
      12th months. Evolution in WT, NP and CRQ were similar in the two groups. No
      relevant side-effects were detected: only two patients stopped treatment (one
      placebo and one AB). CONCLUSION: In an intermittent schedule, although well
      tolerated, at doses of 1 mg/kg/day, AB was not effective in long-term treatment
      of chronic hypoxemia in COPD patients.

PMID- 12814143
TI  - The diffusing capacity in adult cystic fibrosis.
AB  - The value of adjusting the diffusing capacity for the lung volume has been
      demonstrated in a large number of patients with other lung diseases but has not
      been validated in patients with cystic fibrosis (CF). Pulmonary function test
      results on a cohort of 52 adult CF patients were analyzed to determine whether
      the diffusing capacity of carbon monoxide by single breath method (DLCO(SB)) when
      adjusted for alveolar volume (V(A)%), correlated with the severity of pulmonary
      dysfunction. The DLCO(SB) remained within the reference range except in those
      with severe lung impairment (61.88 +/- 15.48%). DLCO(SB) has a significant (P <
      0.05) positive correlation (0.70, 0.67, 048, 0.69 and 0.31, respectively) with
      measures of airflow limitation (FVC%, FEV1%, FEV1/FVC%, MVV%, and sGaw) and
      negative correlation (-0.36 and -0.21, respectively) with measures of air
      trapping (RV% and RV/TLC%). DLCO(SB)/V(A) remained above 100% of predicted
      despite worsening lung disease and did not correlate with other measures of lung
      function. On the other hand, the DLCO(SB) and DLCO(SB)/V(A), when adjusted for
      V(A)%, decreased and were significantly correlated with worsening airflow
      limitation and, to a lesser extent, air trapping. The relatively preserved
      adjusted DLCO(SB) and DLCO(SB)/V(A) values in CF patients up until late in its
      course may be explained the predominant airway involvement, minimal loss of
      alveolar-capillary units, and enhanced V/Q relationship due to claustration in
      CF.

PMID- 12814144
TI  - Chronic obstructive pulmonary disease (COPD) in elderly subjects: impact on
      functional status and quality of life.
AB  - Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity
      and disability. Many studies have investigated factors influencing quality of
      life (QoL) in middle-aged COPD sufferers, but little attention has been given to
      elderly COPD. The aim of the present study was to investigate the impact of COPD
      on QoL and functional status in the elderly. Sixty COPD patients and 58 healthy
      controls over 65 years old were administered Pulmonary Function Tests, 6 min
      Walking Test (6MWD) for exercise tolerance, the Barthel Index and Mini Mental
      State Examination (MMSE) for functional status, the Geriatric Depression Scale
      (GDS) for mood, and the Saint George Respiratory Questionnaire (SGRQ) for QoL.
      FEV1 and PaO2 were reduced in COPD patients. Also the distance walked during 6MWD
      was significantly shorter for patients than controls (282.5 +/- 89.5 vs. 332.9 +/
      95.2 m; P < 0.01). Moreover, COPD patients had significantly worse outcomes for
      the Barthel Index, GDS and SGRQ. The logistic regression model demonstrated that
      a decrease in FEV1 is the factor most strictly related to the deterioration of
      QoL in COPD patients. Mood was also an independent factor influencing QoL. In
      conclusion, elderly COPD patients show a substantial impairment in QoL depending
      on the severity of airway obstruction; symptoms related to the disease may be
      exaggerated by mood deflection.

PMID- 12814145
TI  - Coriolus versicolor polysaccharide peptide slows progression of advanced non
      small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer
      deaths, and over 60% of patients present with advanced stages. Although
      polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have
      been reported to have anti-tumor effects, its clinical efficacy has not been
      properly evaluated. METHODS: Double-blind placebo-controlled randomized study to
      evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical,
      Hong Kong) on patients, who had completed conventional treatment for advanced
      NSCLC. RESULTS: Thirty-four patients, with no significant difference in their
      baseline demographic, clinical or tumor characteristics, or previous treatment
      regimes (P>0.05) were recruited into each of the PSP and control arms. After 28
      day treatment, there was a significant improvement in blood leukocyte and
      neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but
      not the control, patients (P<0.05). Although the evaluable PSP patients did not
      improve in NSCLC-related symptoms, there were significantly less PSP patients
      withdrawn due to disease progression, than their control counterparts (5.9 and
      23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction
      attributable to the trial medications. CONCLUSION: PSP treatment appears to be
      associated with slower deterioration in patients with advanced NSCLC.

PMID- 12814146
TI  - Telithromycin in the treatment of community-acquired pneumonia: a pooled
      analysis.
AB  - The efficacy of telithromycin has been assessed in six Phase III studies
      involving adults with mild to moderate community-acquired pneumonia (CAP) with a
      degree of severity compatible with oral therapy. Patients received telithromycin
      800 mg once daily for 7-10 days in three open-label studies (n=870) and three
      randomized, double-blind, comparator-controlled studies (n=503). Comparator
      antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg
      twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological
      outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated
      patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label
      and comparative studies, respectively. Telithromycin treatment was as effective
      as the comparator agents. High eradication and clinical cure rates were observed
      for infections caused by key pathogens: Streptococcus pneumoniae including
      isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus
      influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly
      effective in patients with infections caused by atypical and/or intracellular
      pathogens and those at increased risk of morbidity. Telithromycin was generally
      well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient
      and well-tolerated first-line oral therapy for the empirical treatment of mild to
      moderate CAP.

PMID- 12814147
TI  - Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and
      their molar ratio in patients with chronic obstructive pulmonary disease,
      idiopathic pulmonary fibrosis and healthy subjects.
AB  - BACKGROUND: Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue
      inhibitors of metalloproteinases (TIMPs), are involved in the turnover of
      extracellular matrix. Chronic obstructive pulmonary disease (COPD) and idiopathic
      pulmonary fibrosis (IPF) are inflammatory diseases characterized by excessive
      matrix degradation and tissue fibrosis. We have compared sputum concentrations of
      MMP-9, TIMP-1 and the controlling cytokine tumor necrosis factor (TNF)-alpha in
      patients with COPD, IPF and healthy subjects. METHODS: In a cross-sectional
      analysis, 12 patients with stable COPD, 15 patients with IPF and 14 healthy
      subjects underwent sputum induction. Induced sputum cells were counted and
      concentrations of MMP-9, TIMP-1 and TNF were measured by enzyme immunoassays.
      RESULTS: Sputum neutrophils were markedly elevated in COPD and IPF patients
      compared with controls (P<0.001, both comparisons). Concentrations of MMP-9 and
      the MMP-9:TIMP-1 ratio were increased in COPD (P<0.001 vs. IPF and controls),
      whereas sputum TIMP-1 levels were both elevated in COPD and IPF (P<0.01 vs.
      controls, both comparisons). TNF levels were similar in all three groups (P>0.2,
      all comparisons). MMP-9 concentrations were negatively correlated with airway
      obstruction (FEV1 FVC) in COPD (rho=-0.62, P=0.03), but not with diffusion
      capacity or vital capacity (% predicted) in IPF (rho=-0.06, P=0.85, and rho=-0.3,
      P=0.29, respectively). MMP-9 was positively correlated with sputum neutrophils in
      all patients (rho=0.68, P<0.0001), and with TNF in COPD patients (rho=0.76,
      P=0.004). CONCLUSIONS: These data underline the significance of
      protease/antiprotease imbalance for the pathogenesis of inflammatory lung
      diseases. Despite similar cellular inflammatory patterns both in COPD and IPF
      sputa, marked differences were observed with regard to MMP-9:TIMP-1 balance.

PMID- 12814148
TI  - Cephalometric assessment of craniofacial morphology in Chinese patients with
      obstructive sleep apnoea.
AB  - OBJECTIVE: To compare the differences in craniofacial morphology in Chinese
      patients with and without obstructive sleep apnoea (OSA). METHOD: We performed
      lateral cephalometric radiographs on 94 consecutive patients (77 males) referred
      with snoring or other symptoms suggestive of OSA for polysomnography (PSG).
      Significant OSA was defined as an apneoa-hypopnoea index (AHI) > or = 10/h of
      sleep on overnight PSG. The cephalometric data were compared between those with
      and without significant OSA. RESULTS: (mean +/- SD) There were 69 (56 males) with
      significant OSA with mean age 53 +/- 12 years, body mass index (BMI) 28.6 +/- 5.0
      kg/m2, AHI 36.5 +/- 20.6/h, and minimum SaO2 76 +/- 14%. There were 25 controls
      (21 males) without significant OSA with similar age and BMI. The mandibular plane
      to hyoid bone distance (MPH) and the perpendicular distance from hyoid bone to
      the line connecting C3 vertebra and retrognathion (HHI) were significantly longer
      in the OSA patients. The angle measurement from sella to nasion to point A (SNA)
      was smaller in the OSA group. MPH distance was the only independent variable for
      significant OSA with an odds ratio of 3.47 (95% CI 1.39-8.66). Abnormalities of
      the MPH and SNA were more marked in the OSA patients with BMI > or = 30 kg/m2.
      CONCLUSIONS: Significant differences in craniofacial morphology are noted between
      OSA patients and non-apnoeic controls. An inferiorly positioned hyoid bone and a
      retropositioned maxilla may predispose obese patients to more severe OSA.

PMID- 12814149
TI  - Orthopnea and inspiratory effort in chronic heart failure patients.
AB  - STUDY OBJECTIVE: Orthopnea is a typical feature of patients with chronic heart
      failure (CHF), the factors contributing to it are not completely understood. We
      investigated changes in dyspnea and other respiratory variables, induced by
      altering posture (from sitting to supine) in 11 CHF patients (NYHA classes II-IV)
      and 10 control subjects. METHODS AND RESULTS: We measured dyspnea (Borg scale)
      the diaphragm pressure time product per minute (PTPdi/m, index of metabolic
      consumption), and mechanical properties of the lung (lung compliance (C,L) and
      resistances (R,L). CHF patients also underwent a trial of non-invasive mechanical
      ventilation (NIMV) in the supine position in order to ascertain whether unloading
      the inspiratory muscles could somehow relieve dyspnea. While sitting the
      PTPdi/min was significantly higher in CHF patients than in controls (181 +/- 54
      cm H2O x s/min vs. 96 +/- 32; P<0.05). Assuming a supine position caused no major
      changes in controls, whereas CHF patients showed a significant worsening in
      dyspnea, a rise in PTPdi/min (243 +/- 97 p<0.01) and R,L (4.7 +/- 1.2 cm H2O/L x
      s sitting vs. 7.9 +/- 2.5 supine; P<0.01) and a decrease in C,L (0.08 +/- 0.02
      L/cm H2O sitting vs. 0.07 +/- 0.01 supine; P<0.05). Applying NIMV to supine CHF
      patients significantly reduced the PTPdi/min to 81 +/- 42 (P<0.001). Changes in
      dyspnea, produced by varying position or applying NIMV, were significantly
      correlated with PTPdi/min (r=0.80, P<0.005 and r=0.58, P<0.01, respectively).
      CONCLUSIONS: CHF patients had a higher PTPdi/min than controls when sitting, and
      assuming a supine position induced severe dyspnea, a large rise in R,L, and a
      reduction in C,L so that PTPdi/min increased further. Orthopnea was strongly
      correlated with the increased diaphragmatic effort.

PMID- 12814150
TI  - Characteristics of pulmonary Mycobacterium avium-intracellulare complex (MAC)
      infection in comparison with those of tuberculosis.
AB  - To clarify the clinical features of pulmonary Mycobacterium avium-intracellulare
      complex (MAC) infection, we retrospectively evaluated clinical manifestations,
      laboratory data, chest and maxillary sinus computed tomographic scans and induced
      sputum findings in 26 with MAC infection in comparison with 104 patients with
      tuberculosis (TB) infection. We found that carbohydrate antigen 19-9 (CA 19-9)
      and immunoglobulin A (IgA) in the serum and percentage of neutrophils in the
      sputum were significantly higher, and sinusitis was significantly more frequent
      in patients with MAC compared with patients with TB. MAC infection might be more
      strongly associated with impaired upper and lower airway defense mechanism in
      comparison with TB.

PMID- 12814151
TI  - Connective tissue responses in acute community-acquired pneumonia.
AB  - Circulating connective tissue components including the aminoterminal propeptides
      of type III collagen (PIIINP), type I collagen (PINP) and hyaluronan were
      determined in patients hospitalised for pneumonia of suspected bacterial origin.
      Ninety patients were included, 64 of these were followed prospectively for up to
      21 days after initiation of therapy. Serum PIIINP was determined by RIA, s-PINP
      by ELISA, and s-hyaluronan by a radiometric assay. S-PIIINP rose significantly
      above the zero value within 24 h in both pneumococcal pneumonia (T0: 5.3
      microg/l, 95% CI: 2.7-8.1 microg/l vs. T1: 6.7 microg/l, 95% CI: 3.8-9.1, P<0.01)
      and in pneumonia of unknown aetiology (T0: 4.0 microg/l, 95% CI: 3.6-4.8 vs. T1:
      4.5 microg/l, 95% CI: 3.8-5.1, P<0.05) followed by a gradual decline. At T1, S
      PIIINP was higher in pneumococcal pneumonia compared with pneumonia of unknown
      aetiology (P<0.05). By contrast, s-PINP tended to decline within 24 h in both
      pneumococcal pneumonia (T1: 30 microg/l, 95% CI: 23-40, ns) and in pneumonia of
      unknown aetiology (T1: 32 microg/l, 95% CI: 22-42, ns) followed by a steady
      increase. The PINP antigen size distribution remained constant throughout the
      follow-up period. S-hyaluronan in pneumococcal pneumonia paralleled s-PIIINP
      reaching a peak value on day 1 (121 microg/l, 95% CI: 65-191, P=0.38). There was
      a positive correlation between s-PIIINP and C-reactive protein (CRP). The study
      demonstrates, that community-acquired pneumonia elicits a differentiated
      mesenchymal response, which is turned down in response to successful antibiotic
      therapy.

PMID- 12814152
TI  - Effect of salmeterol xinafoate on lung mucociliary clearance in patients with
      asthma.
AB  - Lung mucociliary clearance is impaired in stable asthma. The long-acting beta2
      agonist salmeterol has been shown in vitro to cause a significant increase in
      ciliary beat frequency. It seemed possible therefore that salmeterol may also
      have a favourable effect on lung mucociliary transport in asthmatic patients.
      Fourteen patients with asthma participated in a double-blind, placebo-controlled,
      crossover study to assess the effect of 2 weeks of treatment with salmeterol MDI
      (50 microg b.d.) on lung mucociliary clearance. The 11 patients who completed the
      study (seven males, four females) had a mean +/- SE age of 50 +/- 4 years, %
      predicted FEV1 of 74 +/- 8% and a tobacco consumption history of 13 +/- 7 pack
      years (seven non-smokers, four exsmokers). Lung mucociliary transport was
      measured by a radioaerosol technique. Pulmonary function indices (FEV1, FVC, and
      PEF) were significantly improved on salmeterol relative to placebo. The main
      radioaerosol finding was a significant increase in the penetration of
      radioaerosol into the lung with 24-h radioaerosol rising from 40 +/- 5% on
      placebo to 49 +/- 4% (P < 0.01) on salmeterol. Despite this increased
      penetration, a slight favourable change occurred in tracheobronchial aerosol
      clearance. This study demonstrates that 2 weeks salmeterol treatment influences
      deposition of particles within the lung by increasing airway patency and
      indicates a beneficial effect of MDI salmeterol on lung mucociliary clearance.

PMID- 12814153
TI  - Influence of smoking on cutaneous delayed-type hyper sensitivity reaction by
      tuberculin skin test.
AB  - Tuberculin test (purified protein derivative) is currently accepted as a standard
      investigation used in the diagnosis of tuberculosis (TB). Although the
      sensitivity of the test is reliable, a substantial number of those subjected to
      screening for TB by such test are cigarette smokers. This study is designed to
      investigate the effect of smoking on cell-mediated delayed-type cellular
      hypersensitivity (DTH) reaction by PPD. Prospective, case-control study was
      conducted at the Chest and TB unit of Chest Hospital Kuwait. The study population
      consisted of 357 healthy volunteers serving as controls and 200 in-patients under
      direct medical supervision and treatment for tuberculosis as cases. The mean age
      was 33.69 +/- 8.6 SD; 286 were current smokers and 271 were lifetime non-smokers.
      PPD test was done using 2TU RT23 SSI-Denmark on all subjects. Median PPD was
      significant among the cases (P=0.03) between smokers and non-smokers and was
      highly significant among the healthy controls (P<0.001). No significant
      difference was seen between median pack years of smoking and PPD levels among the
      patient group (P=0.264) but the difference was significant among the control
      group (P<0.001). Univariate analysis of variance (ANOVA) on PPD, taking into
      account age, pack years of smoking, ethnic groups and BCG scar showed sufficient
      response but was not statistically significant to all these factors. Smoking
      habit does not appear to influence the cutaneous delayed type hypersensitivity
      reaction by tuberculin skin test.

PMID- 12814154
TI  - Detection of Mycobacterium tuberculosis DNA from peripheral blood in patients
      with HIV-seronegative and new cases of smear-positive pulmonary tuberculosis by
      polymerase chain reaction.
AB  - Tuberculosis is still one of the most important cause of mortality and morbidity
      in many countries and there is a need for new methods for accurate and rapid
      diagnosis of tuberculosis. To determine the sensitivity and specificity of
      polymerase chain reaction (PCR) method, we have evaluated Mycobacterium
      tuberculosis DNA in peripheral blood samples with PCR technique in adult patients
      with human immunodeficiency virus (HIV)-negative and new cases of smear-positive
      pulmonary tuberculosis. We investigated the relationship between characteristic
      of the patients, radiological extension of the disease, sputum smear grade,
      presence of cavity, body-mass index (BMI) serum albumin level, total delay time
      and PCR positivity. Forty patients (33 male and 7 female; mean age 37.8 +/- 14.1)
      and 20 healthy control subjects (13 male and 7 female; mean age 35.6 +/- 7.3)
      were enrolled in this study. PCR was positive in 16 of 40 (40%) patients with
      pulmonary tuberculosis and negative in 24 of 40 (60%). None of the healthy
      controls had positive PCR results. The overall sensitivity specificity and
      accuracy of the PCR assay was 40, 100 and 60%, respectively. We found the
      positive correlation between PCR positivity and sputum smear grade (r=0.46,
      P=0.003) radiological extension of the disease (r=0.69, P=0.001), presence of
      cavity (r=0.90, P=0.001). We conclude that the detection of M. tuberculosis DNA
      from peripheral blood by PCR technique is useful for the rapid diagnosis of
      tuberculosis patients with HIV-negative. Hematogenous dissemination was important
      in tuberculosis patients and peripheral blood samples were suitable and easy
      materials. However, standardization of the PCR method must be ensured for the
      diagnosis of tuberculosis.

PMID- 12814155
TI  - The shuttle walk exercise test in idiopathic pulmonary fibrosis.
AB  - The shuttle walk test (SWT) is a validated, incremental walking test for chronic
      obstructive pulmonary disease, but not for idiopathic pulmonary fibrosis (IPF).
      The measurement of maximal oxygen consumption (VO2 max) is considered to be the
      gold standard measurement of functional capacity. This study examines the
      relationship between IPF patients' performance on the SWT and VO2 max. Twenty
      patients were recruited for the study, which consisted of two separate
      experiments. Firstly, the relationship between SWT performance on a conventional
      corridor SWT, with that on a programmable treadmill SWT designed to reproduce the
      corridor SWT was examined (n=10). In the second experiment, the relationship
      between performance on the treadmill equivalent SWT and VO2 max measurements was
      studied (n=10). There was a significant correlation between distance walked on
      the corridor SWT, and that walked on the treadmill equivalent SWT without VO2 max
      measurements (367 m vs. 410 m) (r=0.91, P=0.0003). There was a significant
      correlation between distance walked on the treadmill equivalent SWT (277 m), and
      the directly determined VO2 max (14.87 ml/kg/min) (r=0.74, P=0.01). During both
      experiments, a significant correlation was also observed between baseline PaO2
      and SWT performance, and between DLCO and SWT performance. The shuttle walk test
      is a simple objective measure of functional capacity in IPF patients, which
      should facilitate the evaluation of new therapeutic compounds for IPF.

PMID- 12814156
TI  - Immunohistochemical classification of the localization of laminin in the
      thickened bronchial epithelial basement membrane of deceased bronchial asthma
      patients.
AB  - To ascertain histological changes in the basal lamina of the bronchial epithelial
      basement membrane in patients with severe bronchial asthma, an
      immunohistochemical study was conducted in 43 patients who died of bronchial
      asthma. Antibodies against laminin, a component of the lamina lucida, were
      utilized. The results revealed various patterns for immunoreactivity to laminin
      in the thickened basement membrane layer. We were able to classify these
      reactivities into four patterns. In Pattern A, laminin reactions branched
      vertically in relation to the thickened basement membrane layer. In Pattern B,
      laminin reactions formed lines along the lower margin of the thickened basement
      membrane layer. In Pattern C, laminin reactions formed lines along the upper
      margin of the thickened basement membrane layer. Finally, in Pattern D, no
      laminin reactions were observed. In addition, relationships between
      immunohistological characteristics of laminin and findings such as epithelial
      cell shedding, basal cell proliferation and basement membrane layer thickening
      were investigated. In many Pattern A patients, epithelial cell shedding was
      observed, but goblet cell hyperplasia and basal cell proliferation were barely
      detectable. Conversely, in numerous Pattern D patients, epithelial cell shedding
      was barely seen, but goblet cell hyperplasia and basal cell proliferation were
      marked. Hence, Patterns A and D were on opposite ends of the spectrum of
      morphological characteristics associated with severe bronchial asthma. In
      Patterns B and C, laminin reactions formed lines along the lower and upper margin
      of the thickened basement membrane layer, respectively. However, no marked
      differences existed in epithelial cell shedding and basement membrane layer
      thickening. The present study is thus the first to clarify that laminin reactions
      in the thickened basement membrane layer vary, and this feature is unique to the
      bronchi of patients with severe bronchial asthma.

PMID- 12814157
TI  - Eosinophilic bronchitis as a cause of chronic cough.
AB  - Eosinophilic bronchitis is a recently described condition in patients with
      chronic cough, sputum eosinophilia, normal spirometry and no evidence of
      bronchial hyperreactivity. The aim of the study was to assess the causes of
      chronic cough and to identify the prevalence of eosinophilic bronchitis as a
      cause of chronic cough. Thirty-six patients [mean age 45.4 +/- 14.3 years (range
      16-69 years), M/F: 4/32] with an isolated chronic cough lasting for more than 4
      weeks were recruited from the outpatient clinic. In all patients, after a full
      history and physical examination, blood eosinophil count, eosinophilic cationic
      protein (ECP), serum total and specific IgE levels were measured. Spirometry,
      methacholine provocation test, skin prick tests, ear, nose and throat
      examination, induction of sputum and esophageal pH testing were performed. The
      mean duration of cough was 31.3 +/- 52.3 months. Sputum eosinophilia greater than
      3% was present in 12 (33.3%) patients and they were diagnosed as eosinophilic
      bronchitis. Their induced sputum had a mean eosinophil count of 8.3% and a mean
      ECP level of 98.5 mg x l(-1), which were higher than the others (P=0.003, both).
      The diagnosis of the remaining patients were postnasal drip syndrome in eight,
      gastroesophageal reflux disease in eight, post-infectious cough in two and cough
      variant asthma in one patient. In conclusion, eosinophilic bronchitis is an
      important cause of chronic cough and should be considered in the assessment of
      patients before regarding them as having idiopathic chronic cough.

PMID- 12814158
TI  - One-year safety and efficacy of budesonide/formoterol in a single inhaler
      (Symbicort Turbuhaler) for the treatment of asthma.
AB  - BACKGROUND: A budesonide/formoterol single inhaler has been developed for
      convenient treatment of patients whose asthma is inadequately controlled by
      inhaled glucocorticosteroids alone. OBJECTIVES: To compare long-term safety and
      efficacy of budesonide/formoterol single inhaler with budesonide plus formoterol
      via separate inhalers in adults with asthma. METHODS: In this open, randomized,
      parallel-group 6-month extension conducted in a subset of centres from a previous
      6-month study, patients (n=321) received two inhalations bid of
      budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg delivered dose or
      corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis
      Turbuhaler) via separate inhalers. RESULTS: Significantly fewer patients
      receiving budesonide/formoterol single inhaler withdrew compared with budesonide
      plus formoterol (9 vs. 19%, P=0.008). Incidence and severity of AEs were low and
      similar in both groups. No clinically important differences between groups, or
      changes, were identified in laboratory measurements, vital signs or ECG.
      Treatments produced similar improvements in lung function, ACQ scores and Mini
      AQLQ domains that were maintained throughout 12 months. CONCLUSIONS:
      Budesonide/formoterol in a single inhaler is as safe and effective in the long
      term treatment of asthma as budesonide plus formoterol via separate inhalers. The
      lower number of withdrawals with budesonide/formoterol may reflect better
      adherence to treatment compared with budesonide plus formoterol.

PMID- 12814159
TI  - Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis.
AB  - Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans.
      Thirty-five patients with pulmonary nocardiosis were identified in two tertiary
      referral hospitals. A retrospective review of the patient characteristics,
      clinical and laboratory features including antimicrobial susceptibility at
      diagnosis was carried out. Radiological features derived from chest radiographs
      and CT scans were also documented. In our population, the predominant risk
      factors were immuno-compromised state, corticosteroid therapy, and underlying
      pulmonary pathology. The presenting features were similar to those previously
      described but disseminated infection was not common. The radiological changes
      were diverse and non-specific. Nocardia asteroides was the commonest species.
      Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and
      cotrimoxazole. Co-existing microbial agents are common and reflect the underlying
      complex disorders.

PMID- 12814160
TI  - Exhaled hydrogen peroxide correlates with the release of reactive oxygen species
      by blood phagocytes in healthy subjects.
AB  - Various cells including polymorphonuclear leukocytes, alveolar macrophages and
      type-II pneumocytes may be a source of exhaled hydrogen peroxide (H2O2) in
      airways of humans. H2O2 can convert into hydroxyl radicals leading to
      peroxidative damage of airways structures and formation of volatile
      thiobarbituric acid-reactive substances (TBARs). We tested whether exhalation of
      H2O2 and TBARs by healthy subjects depends on reactive oxygen species generation
      from blood phagocytes. The expired breath condensate (EBC) and blood specimens
      were collected from 41 healthy, never smoked subjects (mean age 20.7 +/- 0.8
      years, 18 men, 23 women) and then the EBC concentration of H2O2 and TBARs and 2 x
      10(-5) M fMLP-provoked whole blood chemiluminescence response was measured. The
      mean concentration of H2O2 and TBARs in EBC was 0.28 +/- 0.17 and 0.04 +/- 0.13
      microM with ratio of positive readings reaching 36/41 and 4/41, respectively. The
      chemiluminescence response to n-formyl-methionyl-leveyl-phenylalanine stimulation
      was obtained in all cases and the following parameters were estimated: basal
      chemiluminescence (bCl); peak chemiluminescence (pCl); absolute light emission
      (aCl); and peaktime. H2O2 levels in EBC positively correlated (Spearmann test)
      with bCl (r=0.41, P<0.01), pCl (r=0.47, P<0.01), aCl (r=0.49, P<0.001), peaktime
      (r=0.52, P<0.001) in the whole group and with bCl (r=0.56, P<0.01), pCl (r=0.67,
      P<0.01), aCl (r=0.66, P<0.01) in men and with aCl (r=0.41, P<0.05) and peaktime
      (r=0.48, P<0.05) in women. No association between exhaled TBARs and blood
      phagocytes activity was found. These results indicate that H2O2 exhalation in
      healthy never smoked subjects depends on ability of blood phagocytes to generate
      reactive oxygen species.

PMID- 12814161
TI  - Interleukin-17 in sputum correlates with airway hyperresponsiveness to
      methacholine.
AB  - BACKGROUND: Interleukin-17 (IL-17) is a novel cytokine secreted by activated
      human memory CD4+ T cells. In vivo IL-17 recruits neutrophils into the airways
      via the release of CXC chemokines (interleukin-8) from bronchial epithelial
      cells. Since neutrophils are implicated in pathogenesis of chronic obstructive
      pulmonary disease (COPD) chronic bronchitis (CB) and asthma, we hypothesized that
      there would be increased concentration of IL-17 in the airways of these patients.
      To test this hypothesis, we measured levels of IL-17 in induced sputum of COPD
      patients, chronic bronchitis and asthmatics and compared them with healthy
      controls. METHODS: Levels of IL-17 in induced sputum were measured via ELISA
      method in 19 COPD, 16 CB, 10 asthma and 11 control subjects. Airway
      responsiveness to methacholine was performed in people with FEV1 higher than 70%
      of predicted. RESULTS: There were no significant differences in IL-17 levels
      between control group and the other groups. However, levels of IL-17 in sputum of
      COPD patients were significantly lower than in asthma (P=0.004) and in CB
      (P=0.01) groups. Medians and (ranges) were as follows: asthma--37.6 pg/ml (18.8
      55.7 pg/ml), CB 293 pg/ml (18.8-49.7 pg/ml) and COPD 24.6 pg/ml (0-34.1 pg/ml).
      Comparison of healthy control subjects (PC20 > 8 mg/ml) to a group with bronchial
      hyperreactivity, which consisted of asthmatics and CB patients, whose PC20 was
      less than 8 mg/ml, revealed that levels of IL-17 were significantly increased in
      the second group (P=0.02). Also, levels of IL-17 were significantly increased
      (P=0.02) in the asthmatic patients with bronchial hyperreactivity compared to
      healthy subjects. Moreover levels of IL-17 in sputum of all studied subjects
      correlated negatively with PC20 (r=-0.51, P=0.002). CONCLUSIONS: According to our
      results IL-17 is probably not involved in pathogenesis of stable COPD, but it may
      play a role in people with airway hyperresponsiveness.

PMID- 12814162
TI  - Successful treatment of theophylline toxicity by upper gastrointestinal
      endoscopy.

PMID- 12814163
TI  - Detection of HCV-RNA in bronchoalveolar lavage from a woman with pulmonary
      fibrosis.

PMID- 12814164
TI  - Airway inflammation in asthma with incomplete reversibility of airflow
      obstruction.
AB  - This study aimed to determine whether there is a persistent or different type of
      airway inflammation in patients with an incomplete reversibility of airflow
      obstruction (IRAO) despite optimal treatment and if so, whether it is associated
      with an accelerated decline of pulmonary function. Fifteen asthmatic patients
      with IRAO, and 23 with complete reversibility of airflow obstruction (CRAO) had a
      spirometry and an induced-sputum (IS) analysis. Past FEV1 values were recorded
      over 2-12 years during periods of stable asthma. Medians (range) for IS cell
      differentials were: lymphocytes, 0(0-3)/1(0-2)%; neutrophils, 56(13-88)/38(3-84)%
      and eosinophils, 2.0(0-82)/4.0(0-68)%, (all P>0.05). Among non-smoking patients,
      those with IRAO had more neutrophils in IS than those with CRAO (P=0.019). Mean
      (+/-SEM) yearly fall in FEV1 in IRAO or CRAO patients was 54+/-21/84+/-16 ml/year
      (P>0.05, predicted age-related decline < or = 26 ml/year, P=0.0008). In the whole
      group of asthmatic patients, decline of FEV1/year was inversely correlated with
      the % neutrophils in sputum (r(s)=-0.436, P=0.008) and, in IRAO patients, with
      the duration of asthma (r(s)=-0.559, P=0.037). In conclusion, persistent airway
      inflammation and increased decline in pulmonary function can be observed in both
      asthmatic patients with IRAO/CRAO and are of similar magnitude. Non-smoking
      patients with IRAO had more neutrophils in IS than CRAO.

PMID- 12814165
TI  - Can we contract multiple sclerosis from our working environment?

PMID- 12814166
TI  - Fatigue associated with multiple sclerosis: diagnosis, impact and management.
AB  - In patients with multiple sclerosis (MS) fatigue is the most common symptom and
      one of the most disabling features. As many as 40% have described it as the
      single most disabling symptom--a higher percentage than weakness, spasticity,
      motor problems, or bowel or bladder problems. The etiology and pathophysiology of
      MS-related fatigue remain unknown. Studies have failed to demonstrate an
      association between MS-related fatigue and the level of disability, clinical
      disease subtype, or gender, although recent data show an association between MS
      related fatigue and depression and quality of life. Imaging studies using
      positron emission tomography suggest that fatigue in MS is related to
      hypometabolism of specific brain areas, including the frontal and subcortical
      circuits. The impact of fatigue on patient functioning and quality of life
      clearly warrants intervention. In addition to nonpharmacologic measures, such as
      exercise and energy conservation strategies, several pharmacologic agents have
      been evaluated for their ability to reduce MS-related fatigue, including
      amantadine, central nervous system stimulants (pemoline), and the novel wake
      promoting agent modafinil.

PMID- 12814167
TI  - T cells from multiple sclerosis patients recognize immunoglobulin G from
      cerebrospinal fluid.
AB  - Idiotopic sequences are created after V, D and J recombinations and by somatic
      mutations during affinity maturation of immunoglobulin (Ig) molecules, and may
      therefore be potential immunogenic epitopes. Idiotope-specific T cells are able
      to activate and sustain the B cells producing such idiotopes. It is therefore
      possible that idiotope-specific intrathecal T cells could help maintain the
      persisting intrathecal synthesis of oligoclonal IgG observed in patients with
      multiple sclerosis (MS). This study was undertaken to examine T-cell responses to
      cerebrospinal fluid (CSF) IgG. Peripheral blood mononuclear cells (PBMC) from 14
      of 21 MS patients and four of 17 control patients with other neurological
      diseases proliferated upon stimulation with autologous CSF IgG, while five and
      three, respectively, responded to serum IgG. By comparison, responses to myelin
      basic protein were recorded in only four MS and three control patients. Data from
      a limited number of patients indicate that the CSF IgG responsive cells were CD4+
      and human leucocyte antigen DR restricted, that PBMC also respond to CSF IgG from
      other MS patients and that the CSF may contain T cells responding to autologous
      CSF IgG. This suggests that CSF IgG, or substances bound to this IgG, may
      represent T-cell immunogens, which could contribute to the intrathecal immune
      response in MS.

PMID- 12814168
TI  - Serum from patients with multiple sclerosis downregulates occludin and VE
      cadherin expression in cultured endothelial cells.
AB  - Disruption of the blood brain barrier (BBB) and transendothelial migration of
      inflammatory cells are crucial steps in the development of demyelinating lesions
      in multiple sclerosis (MS). Occludin and vascular endothelial-cadherin (VE
      cadherin) are two major components of the tight junctions (TJs) in the brain
      microvasculature that help to create the BBB. In the present study, we
      investigated the effect of serum from MS patients on the expression of these two
      junctional markers and on the endothelial integrity. Serum from six MS patients
      in exacerbation, six in remission, and six normal controls (10% by volume) was
      incubated with cultured endothelial cells, and the expression of occludin and VE
      cadherin was measured by immunoblotting. Serum from MS patients in exacerbation
      significantly reduced the expression of occludin and VE-cadherin compared with
      patients in remission and normal controls. This disintegrating effect was more
      pronounced for occludin than for VE-cadherin. We assume that the elevation in
      cytokines or other serum-soluble factors in MS patients in exacerbation likely
      provokes downregulation of occludin and VE-cadherin. This downregulation of TJs
      proteins may, therefore, contribute to the disruption of the BBB in this
      condition.

PMID- 12814169
TI  - Increased plasma homocysteine levels without signs of vitamin B12 deficiency in
      patients with multiple sclerosis assessed by blood and cerebrospinal fluid
      homocysteine and methylmalonic acid.
AB  - OBJECTIVE: The aim of this study was to evaluate if multiple sclerosis (MS) is
      associated with vitamin B12 (cobalamin) deficiency. METHODS: We measured serum
      vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine
      (tHcy) and also cerebrospinal fluid (CSF) MMA and tHcy in 72 patients with MS and
      23 controls. RESULTS: The mean plasma tHcy level was significantly increased in
      MS patients (11.6 micromol/L) compared with controls (7.4 micromol/L) (P =
      0.002). Seven patients showed low serum vitamin B12 levels but only one of them
      had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or
      blood folate levels did not differ between MS patients and controls. We found no
      significant differences in mean values or frequency of pathological tests of
      serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration,
      CSF tHcy or CSF MMA between patients and healthy subjects. There were no
      correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin
      B12, serum MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability
      status, activity of disease, duration of disease or age. CONCLUSIONS: The
      relevance of the increased mean value of plasma tHcy thus seems uncertain and
      does not indicate functional vitamin B12 deficiency. We can not, however, exclude
      the possibility of a genetically induced dysfunction of the homocysteine
      metabolism relevant for the development of neuroinflammation/degeneration. Our
      findings indicate that, regardless of a significant increase in plasma tHcy in MS
      patients, the MS disease is not generally associated with vitamin B12 deficiency
      since we did not find any other factors indicating vitamin B12 deficiency.
      Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12
      status better than serum, are not warranted in MS. We conclude that B12
      deficiency, in general, is not associated with MS.

PMID- 12814170
TI  - Preliminary magnetic resonance study of the macromolecular proton fraction in
      white matter: a potential marker of myelin?
AB  - We report on a new quantitative magnetization transfer (MT) technique that allows
      for the in vivo estimation of the macromolecular proton fraction (f) and the
      bound pool T2 relaxation time (T2b), whilst permitting whole brain coverage. In
      this pilot study, five subjects with multiple sclerosis (MS) and five healthy
      controls were studied. Both f and T2b were significantly different between MS
      lesions and normal control white matter (WM). Relationships between f and T1
      relaxation time [Spearmans rank correlation coefficient (r(s)) = -0.97, P <
      0.001] and f and the magnetization transfer ratio (MTR; r(s) = 0.80, P < 0.001)
      were observed. Compared with MTR, f and T2b have the potential advantage of
      relative independence from MT acquisition protocol while offering more
      pathologically specific information. In particular, f may provide a more direct
      indication of myelin content in WM.

PMID- 12814171
TI  - Benign paroxysmal positioning vertigo in multiple sclerosis: diagnosis,
      pathophysiology and therapeutic techniques.
AB  - OBJECTIVE: To report on the most common causes of vertigo in patients with
      multiple sclerosis (MS) and emphasize appropriate diagnostic techniques and
      treatment interventions. BACKGROUND: True vertigo is estimated to occur in about
      20% of MS patients. Lesions within the vestibular nuclei and in the root entry
      zone of cranial nerve VIII represent the most common locations where
      demyelinating activity can provoke vertigo in patients with MS. However, other
      causes of vertigo should be explored in MS patients in order to avoid unnecessary
      treatment with corticosteroids and vestibular suppressants. Recently, we reviewed
      our four-year experience with new onset vertigo in our university-based MS
      population and found that benign paroxysmal positioning vertigo (BPPV) to be the
      most common cause. All patients diagnosed with BPPV were treated successfully
      with particle repositioning maneuvers. The remaining patients were treated with
      conventional therapies appropriate for the specific diagnosis. CONCLUSIONS:
      Empiric treatments with corticosteroids and/or vestibular suppressants should not
      be employed until all MS patients undergo a careful bedside examination, which
      includes diagnostic positional and, if indicated, particle repositioning
      maneuvers. Here we emphasize the pathophysiology of BPPV and illustrate the
      proper techniques for the diagnostic and therapeutic maneuvers.

PMID- 12814172
TI  - Myelopathy in seronegative Sjogren syndrome and/or primary progressive multiple
      sclerosis.
AB  - OBJECTIVE: The relationship between multiple sclerosis (MS) and Sjogren syndrome
      (SS) is controversial. Nine patients, previously diagnosed with primary
      progressive MS (PPMS) and who fulfilled the diagnostic criteria for SS, are
      described. METHODS: The European classification criteria for SS were used to
      study nine PPMS patients that complained of sicca complex symptoms. The following
      tests were performed: Schirmer test, rose bengal staining, salivary scintigraphy,
      minor salivary gland biopsy and serologic tests (antibodies Ro/SS-A, La/SS-B and
      antinuclear antibodies). RESULTS: The nine patients met criteria to be diagnosed
      with SS (at least four criteria). All patients were women with a mean age of 46.6
      years at symptom onset. Spastic paraparesis was the presenting symptom in all
      patients, and spinal cord magnetic resonance imaging (MRI) showed abnormalities
      in most; anti-Ro and anti-La antibodies were mostly negative. CONCLUSIONS: Some
      MS patients, predominantly women over 45 years of age, with progressive spastic
      paraparesis, antiextractable nuclear antigen antibodies (Ro/SS-A or La/SS-B)
      negative and with abnormalities in spinal cord MRI, may have SS as an additional
      or alternative diagnosis.

PMID- 12814173
TI  - Long-term follow up of patients with clinically isolated syndromes, relapsing
      remitting and secondary progressive multiple sclerosis.
AB  - This paper extends on previous data on prognosis in multiple sclerosis (MS), to
      encompass the entire course of the disease. The first episode suggestive of MS
      [the clinically isolated syndrome (CIS)] was included as a starting point, and
      the speed of secondary progression as an end point. Primary progressive MS was
      not included. Unique preconditions, with one neurological service covering the
      Goteborg district, allowed for establishing a strictly population-based,
      essentially untreated 15-year incidence cohort of 308 MS patients who were
      followed for 25 years. Survival analysis was performed as Kaplan-Meyer graphs,
      and independent predictors were ascertained by Cox regression analysis. A matrix
      of several predictors and end points was created. From CIS, a higher risk of
      developing clinically definite MS (CDMS), secondary progressive course and
      Disability Status Scale 7 (DSS7) was predicted by efferent tract lesions.
      However, less than 25% had reached DSS7 25 years after CIS with pure afferent
      lesions or other favorable predictors. During the first five years, higher
      relapse frequency, as well as incomplete remission of early bouts, predicted
      higher risks of secondary progressive course and DSS7 during follow-up to 25
      years. However, these early predictors were unable to predict the rate of
      progression, which seems to contain an element of the disease process
      unassociated with its early events. Only late predictors, such as a shorter time
      from onset to secondary progression (1-10 years) and a higher number of
      functional systems involved at onset of progression predicted a faster
      progression rate. Predictors from this study could be used to refine historically
      controlled trials.

PMID- 12814174
TI  - Somatosensory evoked potentials and sensory involvement in multiple sclerosis:
      comparison with clinical findings and quantitative sensory tests.
AB  - Sensory disturbances are one of the most common findings in patients with
      multiple sclerosis (MS). However, they are usually assessed at the standard
      neurological examination only. Quantitative Sensory Tests (QSTs) for temperature
      and vibratory sense allow a more objective evaluation. In a group of 19
      clinically definite MS patients, we compared vibratory and temperature thresholds
      with sensory symptoms or signs at clinical neurological examination and
      somatosensory evoked potentials (SEPs) at the four limbs. The frequency of
      abnormalities of clinical symptoms/signs, vibration threshold and median SEPs
      were 69%, 33% and 55%, respectively. Correlation between degree of abnormality of
      SEPs and clinically assessed vibration sense (V) was statistically significant
      (P<0.007; Spearmann rank coefficient), as well as between SEPs and vibration
      perception threshold (P<0.02). Clinical evaluation of thermal sense did not show
      false positive results compared to quantitative thermal threshold, but false
      negative findings (35%). This study suggests that the combined use of vibration
      threshold and SEPs allows a better objectivation of sensory function, allowing
      the detection of subclinical abnormalities and possibly reducing the number of
      false positive results introduced by clinical assessment. Moreover QSTs are to be
      preferred to clinical evaluation in the assessment of thermal sense, due to their
      superior sensitivity.

PMID- 12814175
TI  - Open-label study of pirfenidone in patients with progressive forms of multiple
      sclerosis.
AB  - BACKGROUND: Pirfenidone is an oral medication with a number of actions affecting
      the immune system. It has been proposed as a possible treatment for multiple
      sclerosis (MS). METHODS: An early-phase study of progressive forms of MS was
      conducted. Pirfenidone was slowly titrated to 2400 mg/day. Safety, clinical,
      quality-of-life, and magnetic resonance image (MRI) outcomes were measured.
      RESULTS: Twenty people were enrolled (13 with secondary progressive and seven
      with primary progressive MS). The mean age was 47.7 years; the mean Expanded
      Disability Status Scale (EDSS) was 5.15; 75% were female. Eighteen patients
      achieved the full dose, although five additional patients eventually had to
      decrease the dose, primarily because of nausea. The Neurologic Rating Scale
      showed a slight worsening, from 69.8+/-8.4 at baseline to 71.8+/-8.9 at one year
      (P = 0.03). Other clinical outcomes remained stable, including the EDSS,
      ambulation index, and nine-hole peg test. The Short-Form Health Survey (SF-36)
      quality-of-life measure remained unchanged. Comparisons of MRI scans at baseline
      and one year found that 715 plaques were unchanged, six were better, and 10 were
      worse. Three patients had plaques that improved and two patients had plaques that
      were worse. There were eight gadolinium-enhancing lesions on the baseline scans
      and 14 on the one-year scans. CONCLUSIONS: Pirfenidone was well tolerated in
      patients with MS. Patients with primary progressive or secondary progressive MS
      tolerated the medication and remained clinically stable during the one year of
      follow up. Placebo-controlled blinded studies are needed to determine clinical
      effectiveness.

PMID- 12814176
TI  - Multiple sclerosis and depression: influence of interferon beta therapy.
AB  - BACKGROUND AND OBJECTIVES: Depression is frequently part of the clinical picture
      of multiple sclerosis (MS). Major depression affects one in two patients with MS
      during the course of their lifetime. Our objectives were to determine first,
      whether interferon beta-1a (IFNbeta-1a) treatment increases the risk or level of
      depression and, secondly, whether depression status and depression evolution are
      related to the clinical characteristics of the disease. PATIENTS AND METHODS: We
      investigated 106 consecutive patients with relapsing remitting MS treated with
      IFNbeta-1a (Avonex). Patients with evidence of severe depression were excluded.
      The depression status, scored on the Beck Depression Inventory (BDI-II)
      (stratified as minimum, mild, moderate or severe level), and disability, scored
      on the Expanded Disability Status Scale (EDSS), were evaluated before and after
      12 months of IFNbeta-1a treatment. RESULTS: At baseline, 85% of patients had a
      minimum or a mild depression status and after 12 months of treatment most of them
      (83%) retained their baseline status. Beck scores before and after treatment were
      not significantly different (P = 0.63). There was no correlation between age,
      gender, duration of illness or EDSS score and Beck score at baseline (P = 0.696).
      Patients with disability progression after one year of IFNbeta-1a treatment had a
      significantly higher Beck score at baseline than patients without disability
      progression (P = 0.003). CONCLUSION: IFNbeta-1a (Avonex) does not seem to
      significantly influence the depression status of MS patients even in those with
      disability progression.

PMID- 12814177
TI  - Sample size estimates for determining treatment effects in high-risk patients
      with early relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Risk factors for short-term progression in early relapsing remitting
      MS have been identified recently. Previously we determined potential risk factors
      for rapid progression of early relapsing remitting MS and identified three groups
      of high-risk patients. These non-mutually exclusive groups of patients were drawn
      from a consecutively studied sample of 98 patients with newly diagnosed MS. High
      risk patients had a history of either poor recovery from initial attacks, more
      than two attacks in the first two years of disease, or a combination of at least
      four other risk factors. OBJECTIVE: To determine differences in sample sizes
      required to show a meaningful treatment effect when using a high-risk sample
      versus a random sample of patients. METHODS: Power analyses were used to
      calculate the different sample sizes needed for hypothetical treatment trials.
      RESULTS: We found that substantially smaller numbers of patients should be needed
      to show a significant treatment effect by employing these high-risk groups of
      patients as compared to a random population of MS patients (e.g., 58% reduction
      in sample size in one model). CONCLUSION: The use of patients at higher risk of
      progression to perform drug treatment trials can be considered as a means to
      reduce the number of patients needed to show a significant treatment effect for
      patients with very early MS.

PMID- 12814178
TI  - Multiple sclerosis characteristics in African American patients in the New York
      State Multiple Sclerosis Consortium.
AB  - The objective of this study was to determine the clinical characteristics of
      multiple sclerosis (MS) in African American (AA) patients in the New York State
      Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of
      18 MS centers throughout New York State organized to prospectively assess
      clinical characteristics of MS patients. AAs comprise 6% (329) of the total
      NYSMSC registrants (5602). Demographics, disease course, therapy, and
      socioeconomic status were compared in AA registrants versus nonAfrican Americans
      (NAA). There was an increased female preponderance and a significantly younger
      age at diagnosis in the AA group. AA patients were more likely to have greater
      disability with increased disease duration. No differences were seen in types of
      MS and use of disease modifying therapies. Our findings suggest a racial
      influence in MS. Further genetic studies that consider race differences are
      warranted to elucidate mechanisms of disease susceptibility.

PMID- 12814179
TI  - The risk of multiple sclerosis in nurses: a population-based epidemiological
      study.
AB  - The incidence of multiple sclerosis (MS) in nurses during the period 1980-1996
      was calculated in a nationwide study. The cohort consisted of 69,428 nurses, 2185
      men and 67,243 women. Sixty (two men and 58 women) with definite MS were
      observed, whereas 69.3 were expected. We found no significant difference between
      the observed and expected number of MS cases (standardized incidence ratio =
      0.87; 95% confidence interval, 0.66-1.12).

PMID- 12814180
TI  - Longitudinal evaluation of depression and anxiety in patients with clinically
      isolated syndrome at high risk of developing early multiple sclerosis.
AB  - We investigated the relationship between emotional changes, brain lesion burden
      and development of multiple sclerosis (MS). Thirty-seven consecutive patients
      with clinically isolated syndrome (CIS) were prospectively assessed with the
      Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory
      (BDI), the State-Trait Anxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI
      scans. BDI and STAI were also administered to 36 age-matched controls. Conversion
      to MS was defined as the occurrence of a clinical relapse. CIS patients were more
      likely to endorse symptoms of anxiety and depression than controls. Baseline
      scores for depression and anxiety did not correlate with the total lesion load
      (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the
      first six months of follow-up. A positive correlation was found between severity
      of depressive scores and the lesion load in the right temporal region (P =
      0.005). After 33+/-6 months of the study entry, patients who had a clinical
      relapse were more frequently depressed (P = 0.001) than those relapse free.
      Emotional disturbances are frequently observed in CIS patients and show a
      tendency towards a normalization in relapse-free patients. The increased rate of
      depressive symptoms observed in patients who developed MS seems to result from a
      combination of psychological and organic features. The lesion load in the right
      temporal region is confirmed as a key area for developing depressive symptoms,
      even in the early phase of the disease.

PMID- 12814181
TI  - Comparative assessment of Yale Single Question and Beck Depression Inventory
      Scale in screening for depression in multiple sclerosis.
AB  - OBJECTIVES: To examine if depression in multiple sclerosis (MS) can be accurately
      recognized using the Yale Single Question (YSQ) screen as compared with the Beck
      Depression Inventory (BDI), a 21-item self-report rating scale for depression. In
      addition, we sought to assess the sensitivity, specificity the positive
      predictive value (PPV) and the negative predictive value (NPV) of the YSQ.
      BACKGROUND: Depression associated with MS is a major contributor to morbidity.
      Screening for depression in patients with MS currently includes the BDI, which
      measures characteristic attitudes and symptoms of depression. However, in a busy
      outpatient clinic, the BDI might not be the most appropriate instrument,
      particularly if depression screening can be assessed accurately using simpler
      techniques that are easy to administer and consume less time. We compared the
      accuracy of the YSQ screen response against the BDI to screen for depression in
      MS patients, in an outpatient setting. METHODS: This is a comparative outcome
      study of two 'instruments' used for screening depression in MS patients in an
      academic outpatient setting. All patients were initially screened for depression
      by asking patients the YSQ--'Do you frequently feel sad or depressed?', followed
      by BDI administration. Depression was defined as a score of > or = 13 on the BDI.
      One hundred and twenty successive patients who presented to the MS clinic at
      Washington University School of Medicine and met the criteria for diagnosis of MS
      were screened for depression. All patients diagnosed as having MS, regardless of
      type, were included in the study. RESULTS: Of the 120 patients studied, a total
      of 49 of 120 were clinically depressed as defined by a BDI cut-off of > or = 13;
      71 of 120 were not. The sensitivity of the YSQ was 32 of 49 = 65.3% with a 95%
      confidence interval (0.50, 0.78), specificity was 62 of 71 = 87.3% (0.77, 0.94),
      PPV was 32 of 41 = 78.0% (0.62, 0.89) and NPV was 62 of 79 = 78.5% (0.68, 0.87).
      Of the 49 patients depressed by BDI criteria, 17 responded 'no' to the YSQ,
      yielding a false-negative rate of 34.7% (0.22, 0.50). The Wilcoxon-Mann-Whitney
      test for difference in age among those on antidepressants compared with those who
      were not showed no statistical difference (P = 0.35). For patients on
      antidepressants, the mean BDI score was 16.0+/-8.9 (mean+/-SD) and 9.5+/-8.7 for
      those not on antidepressants. Differences in BDI scores among patients on
      antidepressants versus those who were not were statistically significant (P <
      0.0001). Patients on antidepressants had significantly higher BDI scores.
      CONCLUSIONS: Our results show that the YSQ cannot replace the BDI as a screening
      instrument for depression in MS. The YSQ could not identify 34.7% of patients who
      were depressed by BDI criteria. However, as reported in a published study, BDI
      missed 30% of cases with early depression in MS when a cut-off of > or = 13 was
      used. The YSQ appears to be specific in ruling out depression when a patient is
      not depressed. MS is a chronic disease and since prevalence of depression varies,
      it is important to screen patients repeatedly over time so as not to miss the
      diagnosis. That BDI scores were higher among those taking antidepressants
      underscores the fact that this subset of patients need to be on medication, but
      the higher scores could also represent a sampling error since the duration of
      antidepressant use was not studied.

PMID- 12814182
TI  - Patient and community preferences for treatments and health states in multiple
      sclerosis.
AB  - OBJECTIVE: To examine preferences for treatments and health states for patients
      with relapsing-remitting MS and members of the community. METHODS: A survey was
      developed to evaluate health-related quality-of-life measures (utilities) for
      three treatments and six MS health states using a utility-elicitation software
      package, U-Titer II. Sixty-two MS patients at two large teaching hospitals in
      Boston, MA, and 67 members of the general community in San Diego, CA, completed
      the health-related quality-of-life survey using a computer. RESULTS: Assessment
      of quality of life decreased as disability level of MS health states increased
      for both respondent groups. Respondents rated less-disabled health states
      relatively highly (> 0.94 for patients and > 0.89 for community respondents).
      Quality-of-life measures for treatments in mean utilities ranged from 0.80 to
      0.96. Patients assigned higher utilities for both MS health states and treatment
      states than community respondents; the ratings became more disparate as health
      states worsened. CONCLUSIONS: On average, respondents assigned utilities to
      currently available treatments for MS that are comparable to those of mild to
      moderate stages of the disease itself. These results underscore the importance of
      including preferences for health states and treatment alternatives in the
      decision to initiate treatment for individual patients or in the evaluation of
      effectiveness or cost-effectiveness of these treatments in patients with MS.

PMID- 12814183
TI  - Unconventional therapy in multiple sclerosis.
AB  - BACKGROUND: The use of unconventional therapies is growing in western countries.
      Few studies on their frequency and rationale among multiple sclerosis (MS)
      patients have been carried out in Europe. OBJECTIVE: To assess the frequency of
      use of unconventional therapies among MS patients and to explore associated
      clinical variables. METHODS: Structured questionnaires were given to 380
      consecutive patients seen at two hospital-based MS clinics in Barcelona. Clinical
      and demographical data were recorded at the same time. The questionnaire inquired
      about demographical features, education, income, use of unconventional therapies
      for MS and satisfaction with conventional medicine both in general and
      specifically in MS. RESULTS: The response rate was 50.78%. Forty-one per cent of
      patients admitted using unconventional therapies during the previous year. Low
      levels of satisfaction with conventional medicine in general and for MS, and
      higher Expanded Disability Status Scale (EDSS) scores (EDSS mean: 4.43 in users
      versus 3.48 in nonusers) were significantly associated with use of unconventional
      therapies. CONCLUSION: Use of unconventional therapies is not rare among MS
      patients, and it is associated with high disability levels and dissatisfaction
      with conventional medicine.

PMID- 12814184
TI  - Assembly, stability and integrity of basement membranes in vivo.
AB  - Basement membranes are layered structures of the extracellular matrix which
      separate cells of various kinds from the surrounding stroma. One of the
      frequently recurring questions about basement membranes is how these structures
      are formed in vivo. Up to a few years ago, it was thought that basement membranes
      were formed spontaneously by a process of self-assembly of their components.
      However, it has now become clear that cell membrane receptors for basement
      membrane components are essential factors for the formation and stability of
      basement membranes in vivo. The present review highlights the modern concepts of
      basement membrane formation.

PMID- 12814185
TI  - Detection of transforming growth factor-alpha and epidermal growth factor
      receptor mRNA and immunohistochemical localization of their proteins in the ovine
      uterus during the early implantation period.
AB  - Accumulated evidence suggests that growth factors of the epidermal growth factor
      (EGF) family play an important role in the murine implantation process. In the
      sheep, however, the uterine distribution of these factors and their receptor, EGF
      receptor (EGF-R), during implantation is not known. This study examined the
      presence of mRNA transcripts and immunohistochemical localization for
      transforming growth factor-alpha (TGF-alpha), the potent EGF-family member, and
      EGF-R in the ovine uterus during the early implantation period. By reverse
      transcriptase-polymerase chain reaction and sequencing of the products, the
      presence of TGF-alpha and EGF-R mRNA transcripts were detected in the endometrium
      on Days 14, 16 and 20 (Day 0 = day of mating). Immunohistochemical analysis
      revealed that the luminal and glandular epithelial cells and some stromal cells
      of the endometrium and the trophectoderm were positive for TGF-alpha and EGF-R on
      Days 14 and 15. Distinct staining for TGF-alpha was observed in the glandular
      epithelium of deep endometrial areas and strong immunoreactivity for EGF-R was
      found in the trophectoderm. On Days 16, 18 and 20, although the staining pattern
      for TGF-alpha was similar to that on the previous days, the immunoreactivity for
      EGF-R in the stromal cells increased and that in the gland decreased. A distinct
      immunoreactivity for EGF-R was found in the trophectoderm throughout the days
      examined. These results suggest that TGF-alpha expressed in the endometrium and
      trophectoderm may exert effects locally on these tissues during implantation in
      sheep. Furthermore, it is speculated that the temporal changes in the uterine EGF
      R distribution may be related to the endometrial microvascular development.

PMID- 12814187
TI  - Immunohistochemical characterization of canine intestinal epithelial and
      mesenchymal tumours with a monoclonal antibody to hepatocyte paraffin 1 (Hep Par
      1).
AB  - Monoclonal antibody hepatocyte paraffin 1 (Hep Par 1) is reported to be highly
      specific and sensitive for hepatocellular tumours of humans and dogs. However, in
      a previous study we observed immunoreactivity for Hep Par 1 in an intestinal
      adenocarcinoma metastatic to the liver. In this paper, we examined normal
      intestine and 57 canine intestinal tumours including adenocarcinomas of the small
      and large intestine, colonorectal polyps, mucinous carcinomas, stromal tumours,
      leiomyosarcomas, fibrosarcoma, plasmacytomas, and osteosarcoma for
      immunoreactivity for Hep Par 1. Normal intestinal epithelial cells were strongly
      labelled, particularly at the base of crypts. However, epithelial cells in small
      intestinal neoplasms had variable reactivity for Hep Par 1. In contrast, normal
      colonic epithelium was seldom labelled, but hyperplastic or neoplastic colonic
      epithelium was usually reactive to Hep Par 1. Five of seven small intestinal
      adenocarcinomas, two of three large intestinal adenocarcinomas, two of three
      mucinous adenocarcinomas, and all (29) rectal polyps were positive for Hep Par 1.
      The staining was diffuse, granular and cytoplasmic. The only non-epithelial
      tumours positive for Hep Par 1 were two of four leiomyosarcomas. Hep Par 1 can be
      used to differentiate hepatocellular from biliary neoplasms but its value in
      differentiating metastatic tumours to the liver is questionable due to the
      reactivity of Hep Par 1 in many intestinal tumours.

PMID- 12814186
TI  - Large quantity of ribosomal RNA exists extracellularly in mouse spleen.
AB  - When BALB/c mouse spleens were gently homogenized in saline, the resultant
      supernatant (without cells and tissue debris) contained significant amount of 28S
      and 18S ribosomal RNA, reaching up to 70% of the total spleen RNA. Haemoglobin
      assays indicated that less than 15% of the spleen cells were lysed during the
      homogenization process, indicating that the majority of the spleen 'supernatant
      RNA' was from the extracellular space of the organ rather than released by the
      splenocytes as a consequence of grinding. Quantitative RNA analysis showed that
      the ratio of spleen supernatant RNA/total RNA of BALB/c mice was inversely
      correlated with age (from approximately 70% at 3 weeks to 45% at 6 months), but
      that of BXSB mice (an animal model for systemic lupus erythematosus) remained at
      about 70% irrespective of age. Methyl Green-Pyronin Y staining of paraffin
      sections of mouse spleen revealed that extracellular RNA was distributed mainly
      in the sinuses of the organ. Culture supernatants of apoptotic splenocytes
      contained significant amounts of RNA, suggesting that the extracellular RNA in
      the spleen might have come from apoptotic lymphocytes. This is supported by the
      fact that 'thymus supernatant' also contained significant amount of RNA. A
      possible correlation between spleen extracellular RNA and autoimmune diseases is
      discussed.

PMID- 12814188
TI  - Human fibroblasts from normal and malignant breast tissue grown in vitro show a
      distinct senescence profile and telomerase activity.
AB  - The telomerase activity and the senescence profile of cultured breast fibroblasts
      from normal human interstitial and malignant stromal tissue were studied in
      comparison with their proliferation and differentiation pattern. Fibroblasts were
      grown either in the presence or absence of a conditioned medium (CM) obtained
      from cultures of the oestrogen receptor-positive breast cancer MCF-7 cell line.
      At different passages (from the 2nd up to the 48th), fibroblasts were examined
      for the telomerase activity by the Telomerase Repeats Amplification Protocol
      (TRAP) assay, for proliferation profile by Ki-67 antigen expression, and the
      myofibroblast or smooth muscle cell-like differentiation pattern by
      immunofluorescence with monoclonal antibodies specific for smooth muscle markers.
      Serial passages of fibroblasts from normal or tumour breast reveal that the
      relationship between the levels of telomerase activity and
      phenotypic/proliferation profile changes with cell subcultivation in a different
      manner in the two cell populations. The fibroblasts from normal tissue completed
      12 passages in a CM-independent way prior to senescence whereas fibroblasts from
      tumour stroma senescence were attained after 48 passages. These cells showed a
      marked decrease of telomerase activity, growth rate and smooth muscle alpha-actin
      expressing myofibroblasts after the 32nd passage. CM treatment of this fibroblast
      population induces a decline in the myofibroblast content, which precedes the
      changes in telomerase activity. Passaged fibroblasts from normal breast tissue
      can be converted to myofibroblasts upon CM treatment whereas those from tumour
      stroma were CM-insensitive. Taken together our data suggest that a heterogeneous
      fibroblast population with different life span is activated/recruited in the
      breast interstitium and poses the problem of a unique activation/recruitment of
      fibroblasts in neoplastic conditions.

PMID- 12814189
TI  - Evidence of a bi-phasic effect of thrombospondin-1 on angiogenesis.
AB  - Contradictory results have been reported regarding the association between
      vascularity (used as an index of angiogenesis) and thrombospondin-1 (TSP-1) in
      human tumours. In previous studies, the reported association was based on the
      estimated average TSP-1 value per tumour, with a sufficient number of specimens
      collectively analysed per tumour type. Given the extent of intra-tumour
      heterogeneity, we determined the association between TSP-1 and vascularity within
      individual specimens, based on the average values of TSP-1 and vascularity in 10
      20 pre-selected areas per tumour. Cells expressing TSP-1 mRNA were visualised by
      in situ hybridisation and quantified by point counting. Vascularity was
      quantified by point counting and vessel density of von Willebrand Factor-positive
      vessels. In 10 ductal breast carcinomas, a direct correlation between TSP-1 and
      vascularity was found in 4 tumours, no correlation in 3 and an inverse
      correlation in 3. The effect of TSP-1 on endothelial cell migration in vitro was
      assessed in the Boyden chamber assay. TSP-1 stimulated cell migration at low
      concentrations (0.1-10 microg/ml) and was inhibitory at high concentrations (25
      100 microg/ml). These results suggest that TSP-1 may elicit a concentration
      dependent, bi-phasic, effect on angiogenesis.

PMID- 12814190
TI  - Immunocytochemistry of glycine in small neurons of the granule cell areas of the
      guinea pig dorsal cochlear nucleus: a post-embedding ultrastructural study.
AB  - The axon terminals of the acoustic nerve contact different part of the cochlear
      nucleus including granule cell areas. Little is known of the cell composition and
      neural circuits of granule cell areas present in the fusiform and upper
      polymorphic layers of the dorsal cochlear nucleus in the guinea pig. The present
      ultrastructural immunocytochemical study exploits the technique of post-embedding
      immunogold and silver intensification to reveal the characteristics of small
      neurons in granule cell areas. Few neurons (Golgi-stellate cells) use glycine as
      inhibitory neurotransmitter which is present in symmetric synaptic boutons with
      pleomorphic and flat vesicles. In contrast, most neurons (granule and unipolar
      brush cells) are not glycine-positive, and presumably not excitatory. Most of the
      large axons (mossy fibres) in granule areas are probably excitatory (glycine
      negative and storing round synaptic vesicles) and contact unipolar brush cells
      forming large synapses or granule cell dendrites by small synapses. A few large
      glycinergic boutons (inhibitory) also contact unipolar brush cells. The
      excitatory circuit of mossy fibre-unipolar brush and granule cells may be
      inhibited by the glycinergic terminals from the few glycinergic cells (Golgi
      stellate neurons) present within the granule cell areas. The latter are not
      contacted by large mossy-like glycine terminals.

PMID- 12814191
TI  - Localization of putative neurotransmitters in the mantle and siphuncle of the
      mollusc Nautilus pompilius L. (Cephalopoda).
AB  - The neurotransmitter supply in the nerve endings of the mantle and the siphuncle,
      i.e. in organs that are responsible for the shell formation in the ectocholeate
      Nautilus pompilius, were investigated with electron microscopical, fluorescence-,
      immuno- and enzyme histochemical methods as well as with high pressure liquid
      chromatography (HPLC). Using antibodies against serotonin and the tetrapeptide
      FMRF-amide, positive reactions were demonstrated immunohistochemically within the
      terminal nerve fibres of the mantle and the vessels of the siphuncle. Enzyme
      histochemical proof of the presence of specific acetylcholinesterase yielded
      positive results in the muscle fibres of the mantle and siphuncle. Additionally,
      in the mantle, glyoxylic acid-induced fluorescence was shown within the nerve
      endings indicating catecholamines as neurotransmitters, whereas in the siphuncle
      such fluorescence did not appear. However, the HPLC-analyses showed that in the
      mantle and also in the siphuncle the content of dopamine is higher than that of
      noradrenaline whereas only traces of adrenaline occur in both organs suggesting
      dopamine as a putative neurotransmitter. Transmission electron microscopical
      examination of the nerve endings of both organs revealed that different types of
      vesicles were distinguished that could be considered as cholinergic, aminergic
      and peptidergic structures.

PMID- 12814192
TI  - A novel embedment-free immunoelectron microscopy technique reveals association of
      apoptosis-regulating proteins with subcellular structures.
AB  - By employing two electron microscopy techniques, postembedding double- and triple
      immunocytochemical gold-labelling combined with embedment-free electron
      microscopy (EF-EM), we have detected previously unreported nuclear and
      cytoplasmic complexes between different proapoptatic proteins in a human cancer
      cell line COLO 205 stimulated to apoptosis by nimesulide, a specific
      cyclooxygenase-2 inhibitor. Experiments with the use of double- and triple
      immunolabelling visualized the colocalization of proapoptotic proteins such as
      Bax with Bid, Bax with Bid and voltage-dependent anion channel protein (VDAC-1),
      and Bax with Bid and caspase-8, on organellar membranes and within the nucleus.
      Application of this technique in combination with EF-EM technique augments our
      knowledge on the precise identification and relationship of subcellular
      structures containing Bax, Bid, VDAC-1 and caspase-8.

PMID- 12814193
TI  - Roots of the Pavlovian Society's missions of the past and present: the Pavlov
      dimension.
AB  - This paper offers an interpretation of the relation between Pavlov's life and
      work and the missions of the Pavlovian Society, both past ("observation and
      observation") and present ("interdisciplinary research on the integrated
      organism"). I begin with an account of Pavlov's life and his influence on
      contemporary thought. I then indicate the relation of some of Pavlov's attitudes
      (e.g., his motto, his epistemological stance) to the Society's past mission. In
      the concluding and most controversial section, I argue for six guiding principles
      derived from Pavlov, to be applied to the Society's mission. These are: (a) a
      confident methodological behaviorism; (b) a significant role assigned to both
      physiological and psychological factors in the prediction and control of the
      integrated organism; (c) approximately equal taxonomic precision of physiological
      and psychological explanatory concepts; (d) distrust of teleological explanatory
      concepts; (e) rejection of psychology's instrumentalist "cognitive paradigm
      shift"; and (f) rejection of the representational theory of knowledge.

PMID- 12814194
TI  - The differential outcomes procedure can interfere or enhance operant rule
      learning.
AB  - The differential outcomes effect--the enhancement of learning and memory
      performance by correlating distinct reinforcers with to-be-remembered events
      (sample stimuli)--has been stated to be one of the most robust phenomena in
      learning psychology. However, in this paper we demonstrate that the correlation
      between unique samples and unique reinforcers can either interfere with or
      enhance learning a spatial matching-rule, dependent on whether these two
      processes are trained concurrently or sequentially. If the Pavlovian conditioning
      (unique sample-reward pairings) occurs before the matching rule is learned
      (sequentially), the conditioned expectations of unique rewards will enhance the
      acquisition of the spatial matching-rule in rats (the differential outcomes
      effect will be observed). However, if rats are required to learn the Pavlovian
      associations and the matching-rule concurrently, they are impaired in acquiring
      the spatial matching-rule. Thus, employing the differential outcomes procedure
      can either enhance or detract from learning and remembering the task rule
      dependent on the nature of the task and order of training. These data suggest
      that under some circumstances learning Pavlovian associations can compete with
      the formation of instrumental behavior.

PMID- 12814195
TI  - Leverpress escape/avoidance conditioning in rats: safety signal length and
      avoidance performance.
AB  - Leverpress escape/avoidance is an excellent model for assessing coping in rats.
      Acquisition of the leverpress response is determined by the interstimulus (signal
      shock) interval, as well as the type and duration of the aversive event. One
      factor that has received less research attention is the safety or feedback
      signal. The safety signal presumably negatively reinforces leverpress responding
      through fear reduction. Here, we present a parametric manipulation of safety
      signal length and avoidance performance. All rats were trained with a 60-s tone
      conditioned stimulus and an intermittent 1-s, 1.0-mA footshock. Training was
      further accomplished with a 1-, 2-, 4-, or 6-min safety signal. Acquisition of
      the avoidance response was comparable at all safety signal durations. Rats
      trained with the shortest safety signal (1 min) exhibited more leverpresses
      during the safe period, a measure of anxiety. Thus, acquisition of the leverpress
      avoidance response was efficient regardless of safety signal duration, even
      though shorter periods were associated with greater anxiety.

PMID- 12814196
TI  - Using eyeblink classical conditioning as a test of the functional consequences of
      exposure of the developing cerebellum to alcohol.
AB  - Exposure of the developing brain to alcohol produces profound Purkinje cell loss
      in the cerebellum, and deficits in tests of motor coordination. However, the
      precise relationship between these two sets of findings has been difficult to
      determine. Eyeblink classical conditioning is known to engage a discrete
      brainstem-cerebellar circuit, making it an ideal test of cerebellar functional
      integrity after developmental alcohol exposure. In eyeblink conditioning, one of
      the deep cerebellar nuclei, the interpositus nucleus, as well as specific
      Purkinje cell populations, are sites of convergence for CS and US information. A
      series of studies have shown that eyeblink conditioning is impaired in both
      weanling and adult rats given binge-like exposure to alcohol as neonates, and
      that these deficits can be traced, at least in part, to impaired activation of
      cerebellar interpositus nucleus neurons and to an overall reduction in the deep
      cerebellar nuclear cell population. Because particular cerebellar cell
      populations are utilized in well-defined ways during eyeblink conditioning,
      conclusions regarding specific changes in the mediation of behavior by these cell
      populations are greatly strengthened. Further studies will be directed towards
      the impact of early exposure to alcohol on the functionality of specific Purkinje
      cell populations, as well as towards brainstem areas that process the tone CS and
      the somatosensory US.

PMID- 12814197
TI  - Does singing promote well-being?: An empirical study of professional and amateur
      singers during a singing lesson.
AB  - This study explored the possible beneficial effects of singing on well-being
      during a singing lesson. Eight amateur (2m, 6f, age 28-53 yrs) and eight
      professional (4m, 4f, age 26-49 yrs) singers who had been attending singing
      lessons for at least six months were included. Continuous ECG was recorded and
      computerized spectral analysis was performed. Serum concentrations of TNF-alpha,
      prolactin, cortisol, and oxytocin were measured before and 30 min after the
      lesson. Five visual analogue scales (VAS, sad-joyful, anxious-calm, worried
      elated, listless-energetic, and tense-relaxed) were scored before and after the
      lesson. In addition, a semi-structured interview was performed. Heart rate
      variability analyses showed significant changes over time in the two groups for
      total power, and low and high frequency power. Power increased during singing in
      professionals, whereas there were no changes in amateurs. This indicates an
      ability to retain more "heart-brain connection." i.e., more cardio-physiological
      fitness for singing in professional singers, compared to amateur singers. Serum
      concentration of TNF-alpha increased in professionals after the singing lesson,
      whereas the concentration in amateurs decreased. Serum concentrations of
      prolactin and cortisol increased after the lesson in the group of men and vice
      versa for women. Oxytocin concentrations increased significantly in both groups
      after the singing lesson. Amateurs reported increasing joy and elatedness (VAS),
      whereas professionals did not. However, both groups felt more energetic and
      relaxed after the singing lesson. The interviews showed that the professionals
      were clearly achievement-oriented, with focus on singing technique, vocal
      apparatus and body during the lesson. The amateurs used the singing lessons as a
      means of self-actualization and self-expression as a way to release emotional
      tensions. In summary, in this study, singing during a singing lesson seemed to
      promote more well-being and less arousal for amateurs compared to professional
      singers, who seemed to experience less well-being and more arousal.

PMID- 12814198
TI  - The mind as a process.
AB  - Essentially all behavior is regulated by the brain in response to information
      received from within the body or from the environment. The tangible structures of
      the brain serve as devices for processing thoughts and emotions as well as
      information. Stored among the interacting neural structures are memories of past
      experiences and responses to them. These intangibles participate in determining
      the decisions made and the actions performed by the brain's structures. There are
      valuable studies of the clinical and neurological effects of environmental
      stimuli, but we need to learn more about the processes that lead to these
      effects. More definitive correlations could be made between environmental stimuli
      and the neurological pathways they create by studying individual's real life
      experiences rather than laboratory simulations alone.

PMID- 12814199
TI  - Occupation and larynx and hypopharynx cancer: an international case-control study
      in France, Italy, Spain, and Switzerland.
AB  - OBJECTIVE: To estimate risks for laryngeal/hypopharyngeal cancer associated with
      occupational titles and industrial activities. METHODS: A multicentre population
      based case-control study was conducted in the early 1980s in six southern
      European areas. Analyses included 1010 male cases and 2176 controls. Odds ratios
      (ORs) (adjusted for age, study area, tobacco consumption, and alcohol
      consumption) were estimated for 156 occupations and 70 industrial activities.
      RESULTS: An excess risk has been confirmed for categories of construction
      workers, potters (OR: 5.91, 95% confidence intervals 1.46-24.0), butchers (2.53,
      1.22-5.22), barbers (2.33, 1.00-5.40), laborers not otherwise specified (1.52,
      1.12-2.06), as well as for men who had been employed in railway transport (1.52,
      0.97-2.39), shipbuilding (2.05, 0.89-4.94), and hotels (2.06, 0.89-4.75). An
      association was also found for shoe finishers (3.23, 0.75-13.9), loggers (2.07,
      0.87-4.90), and some groups of metal workers. ORs for loggers, butchers, railway
      transport workers, laborers, and reinforced concreters increased with duration of
      employment. The suggestion of a risk for machine operators among woodworkers
      (3.10, 0.92-10.5) conflicts with previous findings. No significant excess of risk
      was found for categories previously reported to be associated with laryngeal and
      hypopharyngeal cancer, such as drivers, mechanics, welders, machinists, and
      painters. CONCLUSIONS: The present study provides additional evidence to the
      hypothesis of a risk of cancer of the larynx/ hypopharynx for workers engaged in
      jobs in the construction, metal, textile, ceramic, and food industries and in
      railway transport. Loggers were also found at risk; a previously unreported
      finding.

PMID- 12814200
TI  - Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in
      an international case-control study in France, Italy, Spain and Switzerland.
AB  - OBJECTIVE: To investigate the effect of exposure to occupational agents on the
      risk of hypopharyngeal/laryngeal cancer. METHODS: Case-control study conducted
      during 1979-1982 in six centres in South Europe. An occupational history and
      information on exposure to non-occupational factors were collected for 1010 male
      cases of hypopharyngeal/ laryngeal cancer as well as for 2176 population
      controls. The exposure to 10 occupational agents was assessed through a job
      exposure matrix. As occupational histories had been collected since 1945 major
      analyses were restricted to subjects aged less than 55 years (315 cases and 819
      controls). RESULTS: Significant elevated risks adjusted for non-occupational
      variables (smoking, alcohol consumption and diet) and other occupational
      exposures were consistently found for organic solvents (odds ratio (OR) for ever
      exposure: 1.7, 95% confidence interval: 1.1-2.5) and asbestos (OR: 1.6, 1.0-2.5).
      A significant positive trend for both probability of exposure and duration was
      found for exposure to solvents. A positive association between exposure to
      formaldehyde and laryngeal cancer was also suggested. No association was found
      for exposure to arsenic and compounds, chromium and compounds, and polycyclic
      aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not
      show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7).
      CONCLUSIONS: In our study occupational exposure to solvents was associated with
      an increased risk of hypopharyngeal/laryngeal cancer. Results also provide
      additional evidence of an excess of risk for exposure to asbestos.

PMID- 12814201
TI  - Postmenopausal hormone therapy and risk of breast cancer by histologic type
      (United States).
AB  - OBJECTIVE: Postmenopausal hormone use and risk of breast cancer by histopathology
      was examined in a large multi-centered population-based case-control study.
      METHODS: Women younger than 75 years newly diagnosed with invasive breast cancer
      between 1988 and 1991 were identified from statewide tumour registries in
      Wisconsin, Massachusetts, New Hampshire, and Maine. Only postmenopausal women
      were included in this analysis. Breast cancer cases (lobular (n = 219), ductal,
      NOS (n = 2172), and specific ductal subtypes (n = 242)) were compared with
      randomly selected population controls (n = 3179) using adjusted multi-variable
      polytomous logistic regression to estimate odds ratios (OR) and 95% confidence
      intervals (95%CI) for each histology. RESULTS: Lobular carcinoma was associated
      with recent (within 2 years) estrogen therapy (OR: 1.8, 95% CI: 1.0-3.4) and
      recent use of combined estrogen-plus-progestin therapy (OR:3.6, 95%CI: 1.8-7.6).
      Risk of ductal carcinoma was not associated with recent use of either estrogen
      alone (OR: 0.9, 95% CI: 0.7-1.2) or combined therapy (OR:0.9, 95% CI: 0.6-1.3).
      No associations were found with ductal subtypes. CONCLUSIONS: The association
      between postmenopausal hormone use and risk of breast cancer may depend on
      histopathology. Of particular interest is the association between combined
      hormone therapy and increased risk of lobular carcinoma. This lesion is
      increasingly common but, nonetheless, comprises fewer than 10% of invasive breast
      cancers.

PMID- 12814202
TI  - Breast cancer risk communication: challenges and future research directions:
      workshop report (United States).
AB  - The Dana-Farber Harvard Cancer Center and the Harvard Center for Cancer
      Prevention convened a conference in May 2002 to review the current issues in
      breast cancer risk communication and to identify directions for future research.
      Specific topics included risk communication theory, use of risk models in breast
      cancer screening, genetic testing, decision-making regarding breast cancer
      treatment, and the role of popular media in risk communication. This report
      describes the proceedings of the conference.

PMID- 12814203
TI  - Risk of hepatocellular carcinoma and habits of alcohol drinking, betel quid
      chewing and cigarette smoking: a cohort of 2416 HBsAg-seropositive and 9421 HBsAg
      seronegative male residents in Taiwan.
AB  - OBJECTIVES: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma
      (HCC) in the world. The specific aim of this study is to assess the associations
      between the risk of HCC and habits of alcohol drinking, betel quid chewing and
      cigarette smoking among subjects with and without chronic HBV infection. METHODS:
      A total of 11,837 male residents in Taiwan were recruited in this community-based
      cohort study. Hepatitis B surface antigen (HBsAg) and antibody against hepatitis
      C virus (anti-HCV) in serum were determined by enzyme immunoassay, and the habits
      of alcohol drinking, betel quid chewing and cigarette smoking were collected
      through standardized personal interview according to a structured questionnaire.
      During the follow-up period of 91,885 person-years, 115 incident HCC cases were
      identified through data linkage with national cancer registry profile. The
      relative risk (RR) of developing HCC for habits of various substance use and
      chronic HBV infection were estimated by Cox's proportional hazards regression
      analyses. RESULTS: Significantly increased HCC risk was observed for
      seropositives of HBsAg or anti-HCV, alcohol drinkers, betel quid chewers and
      cigarette smokers. There was a significant dose-response relationship between the
      risk of HCC and the number of habits of substance use. The highest multivariate
      adjusted HCC risk was observed among HBsAg-seropositive substance users (RRs:
      17.9-26.9), followed by HBsAg-seropositive non-users (RRs: 13.1-19.2), HBsAg
      seronegative substance users (RRs: 1.6-2.7) and HBsAg-seronegative non-users
      (referent with RR = 1). The multivariate-adjusted relative HCC risks for habits
      of use of various substances were more profound among HBsAg-seronegatives than
      HBsAg-seropositive ones. CONCLUSION: Habitual alcohol drinking, betel quid
      chewing and cigarette smoking are associated with an increased risk of HCC.
      Abstinence from substance use is important for the prevention of HCC in areas
      where chronic HBV infection is endemic.

PMID- 12814204
TI  - Trends in the incidence of ocular melanoma in the United States, 1974-1998.
AB  - BACKGROUND: A recent report noted a fourfold risk of ocular melanoma associated
      with employment in occupations involving use of cellular telephones. METHODS: To
      aid interpretation of this finding, and clarify how subsite-specific temporal
      variation in incidence of ocular melanoma compares with that for cutaneous
      melanoma, we examined time trends in the incidence of melanoma among whites in
      the United States, based on data collected through the surveillance,
      Epidemiology, and End Results (SEER) program for 1974-1998. RESULTS: The
      incidence of ocular melanoma decreased over time in both sexes, with no
      indication of a recent increase during the 1990s. The annual percent change was 
      0.7% for males (95% confidence interval: -2.3, 0.9) and -1.2% for females (95%
      confidence interval: -2.5, 0.0). Time trends appeared to differ by subsite of
      ocular melanoma; rates were flat for the choroid, decreased for the ciliary body,
      and increased for the conjunctiva (among males only) beginning in the 1980s. In
      contrast, all subsites of cutaneous melanoma, including the face and adjacent
      areas, showed marked increases in incidence over the observation period.
      CONCLUSIONS: The dramatic increase in use of cellular telephones has not been
      accompanied by an increase in the incidence of ocular melanoma. Further study is
      required to explain the different time trends for subsites of ocular melanoma,
      and for ocular versus facial and other cutaneous melanomas.

PMID- 12814205
TI  - Cancer incidence and mortality in Ontario First Nations, 1968-1991 (Canada).
AB  - OBJECTIVE: To determine cancer incidence and mortality rates in Ontario First
      Nations (FN) people (native Indians) during 1968-1991 and to compare these with
      rates in the Ontario population. METHODS: A cohort of 141,290 Ontario FN was
      created from registration files maintained by the Canadian government. Cancers
      and deaths were ascertained by linkage to the provincial cancer registry and
      mortality file, which also provided general population comparison data. RESULTS:
      Cancer incidence was significantly lower in FN compared to the general population
      for all cancer (rate ratio (RR) = 0.72 for females; 0.62 for males), breast
      cancer (RR = 0.54), lung cancer in men (RR = 0.68), prostate cancer (RR = 0.57)
      and colorectal cancer (RR = 0.58 and 0.57 in men and women, respectively). Rates
      were significantly higher in FN for cervical cancer (RR = 1.73) and gallbladder
      cancer (2.05 and 2.20 in men and women, respectively). Incidence rates increased
      significantly in FN people between 1968-1975 and 1984-1991 for all cancer and for
      the major cancers (breast, lung, prostate and colorectal). Colorectal cancer rate
      ratios were significantly higher in 1984-1991 than in 1968-1975, indicating
      converging incidence rates. Patterns of cancer mortality were similar.
      CONCLUSIONS: These trends are compatible with a population in epidemiologic
      transition to the Euro-American disease pattern which is dominated by chronic
      diseases.

PMID- 12814207
TI  - Alcohol intake, drinking patterns and risk of postmenopausal breast cancer in
      Denmark: a prospective cohort study.
AB  - OBJECTIVE: The available epidemiological evidence indicates that drinking alcohol
      per se is associated with breast cancer. However, it has not been investigated
      how the breast cancer risk for a given total alcohol consumption depends on the
      drinking frequency. METHODS: Within the prospective study on 'Diet, Cancer and
      Health', we examined the relationship between breast cancer, intake of total
      alcohol and frequency of drinking among 23,778 postmenopausal women, among whom
      425 cases of breast cancer accrued during a median follow-up of 4.8 years.
      RESULTS: The dose-response relationship between total alcohol intake and breast
      cancer showed an increase in the rate ratio of 1.10 per 10 g/day (95% CI: 1.04
      1.16) with no evidence for differences by type of alcohol beverage. No
      interaction was found between drinking frequency and total alcohol intake in the
      risk of breast cancer (p = 0.40). CONCLUSIONS: The present study supports
      previous ones in showing a monotonic increase in the risk of breast cancer among
      postmenopausal women with increasing average daily intake of alcohol, and this
      relationship with alcohol intake did not depend on drinking frequency.

PMID- 12814206
TI  - Tissue levels of fish fatty acids and risk of colorectal adenomas: a case-control
      study (Netherlands).
AB  - Epidemiological and animal studies have suggested that a high ratio of n-3 fish
      fatty acids to arachidonic acid (AA), might protect against colorectal
      carcinogenesis. Competition of n-3 and n-6 fatty acids, especially AA, for the
      enzyme cyclooxygenase-2 may be responsible for this effect. To examine the
      relation between fish intake and colorectal adenomas, data from a Dutch case
      control study were analysed. All 52 cases and 57 controls filled out a food
      questionnaire, underwent a full colonic examination and have had a fat biopsy
      from the buttock. Intake of fish and fish fatty acids was inversely associated
      with colorectal adenomas although not statistically significant. For the ratio of
      fish fatty acids to AA, the ORs in the second and third tertile were 1.2 and 0.8
      (p-trend = 0.78). Tissue levels of fish fatty acids were inversely associated and
      tissue levels of AA were positively associated with adenomas, although not
      statistically significant. However, the OR for the ratio of fish fatty acids to
      AA was 0.2 in the second and third tertile (p-trend = 0.002). In line with the
      hypothesis, a high ratio of fish fatty acids to AA in adipose tissue was
      associated with a lower risk of colorectal adenomas.

PMID- 12814208
TI  - Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin
      like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).
AB  - OBJECTIVE: To investigate the association of prediagnostic circulating levels of
      C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins 
      1 and -2, as indicators of the biologically active IGF-I concentration, with risk
      of developing ovarian cancer. METHODS: The study was nested within three
      prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Case
      subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed
      at least one year after blood donation. For each case, two control subjects were
      selected, matching the case subject on cohort, menopausal status, age and date of
      recruitment (n = 263). Only women who did not use exogenous hormones at blood
      donation were included in the study. RESULTS: Odds ratios and their 95%
      confidence intervals for risk of developing ovarian cancer over quartiles of
      peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66
      (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10
      (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01
      (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had
      ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1
      and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively.
      CONCLUSIONS: This study does not support an independent direct etiological role
      of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective
      effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before
      age 55.

PMID- 12814209
TI  - Rapid N-acetyltransferase 2 imputed phenotype and smoking may increase risk of
      colorectal cancer in women (Netherlands).
AB  - OBJECTIVE: The relationship between smoking and colorectal cancer risk and
      whether such effect is modified by variations in the NAT2 genotype is
      investigated. METHODS: In the prospective DOM (Diagnostisch Onderzoek
      Mammacarcinoom; 27,722 women) cohort follow-up from 1976 until 1987 revealed 54
      deaths due to colon or rectal cancer, and follow-up from 1987 to 01-01-1996
      revealed 204 incident colorectal cancer cases. A random sample (n = 857) from the
      baseline cohort was used as controls. Four NAT2 restriction fragment length
      polymorphisms (RFLPs) were analysed using DNA extracted from urine samples. Rapid
      or slow acetylator phenotype status was attributed to individuals. RESULTS:
      Smoking may increase the risk for colon cancer (RR = 1.36, 95% CI 0.97-1.92) as
      well as for rectal cancer (RR = 1.31, 95% CI 0.76-2.25), although not
      statistically significant. Rapid NAT2 acetylation did not increase colorectal
      cancer risk, but in combination with smoking the risk was statistically
      significant increased, compared to women who had a slow NAT2 imputed phenotype
      and never smoked (RR = 1.56, 95% CI 1.03-2.37). For colon cancer, but not for
      rectal cancer the increased risk was statistically significant (RR = 1.67, 95%
      CI, 1.05-2.67 versus RR = 1.30 95% CI 0.63-2.68). CONCLUSIONS: Our study points
      to smoking as a risk factor for colon and rectal cancer and, in addition,
      especially in women with rapid NAT2 imputed phenotype.

PMID- 12814210
TI  - Re: Breast-feeding and neuroblastoma, USA and Canada.

PMID- 12814211
TI  - Cultural desire: the key to unlocking cultural competence.

PMID- 12814212
TI  - Preparing for the adjustment of going from student to nurse practitioner.

PMID- 12814213
TI  - Engendering community: learning to live together.

PMID- 12814214
TI  - Ensuring cultural diversity among California nurses.
AB  - The California Strategic Planning Committee for Nursing cultural diversity work
      group surveyed deans and directors from RN prelicensure and vocational nurse
      education programs in California in 1998. With a 49% response rate, key survey
      findings were that 48% of programs were actively recruiting ethnically diverse
      students using a variety of strategies; various approaches were being used to
      retain students; barriers to student success were primarily financial and
      educational; and most programs included curricular content and programming
      designed to ensure culturally competent and sensitive graduates.

PMID- 12814215
TI  - Measuring cultural awareness in nursing students.
AB  - Recognizing the need for a valid and reliable way to measure outcomes of a
      program to promote multicultural awareness among nursing faculty and students,
      the authors developed a cultural awareness scale. In the first phase of the
      study, a scale consisting of 37 items was generated from a literature review on
      cultural awareness, sensitivity, and competence in nursing. A Cronbach's alpha
      reliability coefficient of .91 was obtained from a sample of 72 student nurses.
      In the second phase, the items were presented to a panel of experts in nursing
      and culture to determine content validity. A content validity index of .88 was
      calculated, and the total number of items on the scale was reduced to 36. The
      scale then was administered to 118 nursing students. Data from the two samples
      then were combined, and factor analysis was conducted to support construct
      validity. Cronbach's alpha for the combined samples was .82.

PMID- 12814216
TI  - An education in racism.
AB  - Lack of diversity in nursing doctoral programs compromises the quality of
      doctoral education and perpetuates the shortage of faculty of color in nursing
      schools. To help understand the contexts that contribute to this lack of
      diversity, this study examined the experiences of 9 women of color in nursing
      doctoral programs. The aim of the study was to describe the experiences,
      challenges, and understandings of women of color in nursing doctoral programs.
      Analysis of interview data revealed that racism was a pervasive and harmful
      influence on participants and that this influence was largely invisible to Euro
      American faculty and students. These findings highlight the need for faculty and
      students to critically reflect on their own racism as an important first step in
      challenging the status quo of racism in nursing education. "When I dare to be
      powerful--to use my strength in the service of my vision, then it becomes less
      and less important whether I am afraid." - Audre Lorde (cited in Humbolt State
      University, n.d.).

PMID- 12814217
TI  - "I saw it in a different light": international learning experiences in
      baccalaureate nursing education.
AB  - Health care providers in the United States are faced with delivering care to an
      increasingly diverse population. Nursing leaders and their respective
      organizations long have recognized the need to prepare nurses who understand the
      effects of the growing global community. Inclusion of cultural content in theory
      courses and clinical assignments in diverse settings are two ways to increase
      student nurses' cultural competency. This study explored the experiences of
      nursing students and faculty mentors who sought to increase their cultural
      competence through participation in a short-term immersion learning project in
      Central America. Analysis of data gathered through interviews and journal entries
      identified three themes--being "other," "I was already a nurse," and expanding my
      worldview.

PMID- 12814218
TI  - Using role play to develop cultural competence.
AB  - Role play is a useful teaching strategy for nursing education. This strategy can
      simulate patient behaviors, as well as demonstrate nursing interventions that
      students must learn to be clinically competent. Role play is a dramatic technique
      that encourages participation to improvise behaviors that may be encountered in
      nurse-patient situations. Using this technique, participants may test behaviors
      and decisions in an experimental atmosphere without risk of negative effects in a
      relationship. Role play is useful in developing cultural competence because
      participants may experience diverse roles. Cultural competence is the ability to
      care for patients in a culturally sensitive and appropriate manner. In role play,
      students may participate as culturally diverse patients or as nurses encountering
      patients from different cultures. Various teaching strategies facilitate
      successful use of role play in the classroom, including defining a time frame,
      selected roles, specific objectives, references, and grading criteria. To
      optimize learning, the importance of exploration and analysis must be emphasized.
      Many benefits and potential problems accompany use of role play.

PMID- 12814219
TI  - The Byrne Guide for Inclusionary Cultural Content.
AB  - This article describes the background for development of The Byrne Guide for
      Inclusionary Cultural Content, which may help nurse educators evaluate and create
      instructional materials that include diverse groups. Curricular implications of
      diversity, as well as six categories of instructional bias are included in the
      background of information that contributed to the development of this Guide.

PMID- 12814220
TI  - Diabetes mellitus and the dental pulp.
AB  - This study attempts to evaluate the oral manifestations of and the limited
      available dental pulp information on diabetes mellitus, a common metabolic
      disorder of carbohydrate and lipid metabolism affecting over 16 million
      Americans. Diabetics are particularly prone to bacterial or opportunistic
      infections. This vulnerability is caused by a generalized circulatory disorder
      whereby the blood vessels are damaged by the accumulation of atheromatous
      deposits in the tissues of the blood vessels lumen. In addition, blood vessels,
      particularly capillaries, develop a thickened basement membrane, which impairs a
      leukotactic response, and there is a decrease in the polymorphonuclear leucocyte
      microbicidal ability and failure to deliver the humoral and cellular components
      of the immune system. Because the dental pulp has limited or no collateral
      circulation, it is more prone to be at risk for infection. Clinical and
      radiographic studies by other investigators have shown that there is a greater
      prevalence of periapical lesions in diabetics than in nondiabetics. In a study of
      252 diabetics with poor glycemic control, a high rate of asymptomatic tooth
      infection was found. Inflammatory reactions are greater in diabetic states, and
      the increased local inflammation causes an intensification of diabetes with a
      rise in blood glucose, placing the patient in an uncontrolled diabetic state.
      This often requires an increase in insulin dosage or therapeutic adjustment.
      Removal of the inflammatory state in the periodontium created a need for a lesser
      amount of insulin for glycemic control. Thus, it is essential to remove all
      infections including those of the dental pulp. When diabetes mellitus is under
      therapeutic control, periapical and other lesions heal as readily as in
      nondiabetics.

PMID- 12814221
TI  - Bacteroides forsythus in primary endodontic infections as detected by nested PCR.
AB  - The purpose of this study was to investigate the prevalence of Bacteroides
      forsythus in primary endodontic infections using a species-specific nested
      polymerase chain reaction assay. Samples were collected from 50 teeth having
      carious lesions, necrotic pulps, and different forms of periradicular diseases.
      DNA extracted from the samples was initially amplified using universal 16S rDNA
      primers. A second round of amplification used the first polymerase chain reaction
      products to detect a specific fragment of B. forsythus 16S rDNA. B. forsythus was
      detected in 13 of 22 asymptomatic cases (59.1%), 4 of 10 root canals associated
      with acute apical periodontitis (40%), and 9 of 18 cases diagnosed as acute
      periradicular abscesses (50%). There was no relationship between the presence of
      B. forsythus and the occurrence of symptoms. In general, this bacterial species
      was detected in 26 of 50 samples of endodontic infections (52%). The findings of
      this study support the assertion that this bacterial species is associated with
      infections of endodontic origin and suggest that B. forsythus may be involved in
      the pathogenesis of different forms of periradicular lesions.

PMID- 12814222
TI  - Calretinin expression in odontogenic cysts.
AB  - Calretinin is a calcium-binding protein with a possible role as a calcium buffer,
      calcium-sensor, or regulator of apoptosis. Calretinin is expressed in neural
      tissue, is a specific marker of mesothelial cells, and has been demonstrated in
      the odontogenic epithelium during odontogenesis in rat molar tooth germs.
      Moreover, it has been found to be expressed in a high proportion of solid,
      unicystic, and multicystic ameloblastomas, whereas, on the contrary, no positive
      staining has been found in odontogenic keratocysts, residual cysts, and
      dentigerous cysts. The purpose of this study was to evaluate calretinin
      expression in radicular cysts, follicular cysts, orthokeratinized keratocysts,
      and parakeratinized keratocysts. A total of 70 odontogenic cysts, 24 radicular
      cysts, 24 follicular cysts, and 22 odontogenic keratocysts (10 orthokeratinized
      keratocysts, 12 parakeratinized keratocysts) were evaluated. All the radicular
      cysts, follicular cysts, and orthokeratinized keratocysts were negative. However
      in 8 of 12 parakeratinized keratocysts, there was a positivity to calretinin in
      the parabasal-intermediate layers of the cyst epithelium. This positivity to
      calretinin in the parabasal layers in parakeratinized keratocysts, similar to
      that found for other markers like PCNA and p53, could point to an abnormal
      control of the cell cycle and could help to explain the differences in the
      clinical and pathologic behavior of odontogenic keratocysts, in particular the
      differences found between orthokeratinized keratocysts and parakeratinized
      keratocysts.

PMID- 12814223
TI  - Adrenergic regulation of capsaicin-sensitive neurons in dental pulp.
AB  - Alpha adrenergic agonists (e.g. vasoconstrictors) represent one of the most
      commonly used drug classes in dentistry. Although adrenergic agonists have potent
      vascular effects, recent studies suggest that capsaicin-sensitive nociceptors may
      express adrenoceptors, suggesting that these drugs may directly modulate the
      function of an important class of pain-signaling neurons in peripheral tissues.
      In this study, we tested the hypothesis that adrenergic agonists inhibit
      activation of peripheral terminals of capsaicin-sensitive fibers innervating
      dental pulp. Pretreatment with epinephrine or clonidine significantly inhibited
      capsaicin-evoked release of immunoreactive calcitonin gene-related peptide from
      superfused bovine dental pulp. These studies suggest that adrenergic agonists may
      reduce postoperative pain in part via a direct inhibition of capsaicin-sensitive
      nociceptors. This finding may lead to the development of selective, peripherally
      acting, adrenergic analgesics. Moreover, because neuropeptide release alters
      blood flow, it is possible that the vascular effects of these drugs are caused by
      both vasoconstriction and inhibition of peripheral neuropeptide release.

PMID- 12814224
TI  - The antimicrobial effect of MTAD: an in vitro investigation.
AB  - Pulp and periradicular diseases are of microbial origin. To effectively clean the
      root canal system a disinfecting agent must be able to penetrate into difficult
      to-reach areas and kill microorganisms with minimal damage to the host tissues.
      The purpose of this investigation was to test the ability of a mixture of a
      tetracycline isomer, an acid, and a detergent (MTAD) to kill Enterococcus
      faecalis and compare its efficacy to that of sodium hypochlorite (NaOCl) and
      ethylene diamine tetraacetic acid (EDTA). The zones of inhibition and minimum
      inhibitory concentrations were measured for these solutions. Measurement of zones
      of inhibition and determination of the minimum inhibitory concentrations showed
      that MTAD is as effective as 5.25% NaOCl and significantly more effective than
      EDTA (p < 0.0001). Furthermore, MTAD is significantly more effective in killing
      E. faecalis than NaOCl when the solutions are diluted (p < 0.0001). Measurement
      of the minimum inhibitory concentrations demonstrated that although MTAD is still
      effective in killing E. faecalis at 200x dilution, NaOCl ceases to exert its
      antibacterial activity beyond 32x dilution. EDTA did not exhibit any
      antibacterial activity. Based on the results of this study, it seems that MTAD is
      an effective solution in eradicating E. faecalis.

PMID- 12814225
TI  - Inductively coupled plasma-emission spectroscopy and atomic absorption for the
      use of elemental analysis of a root canal after lasing with a holmium:YAG laser.
AB  - It has been reported in the literature that after lasing dentin the dentin
      surface has a glassy or globular appearance. Many authors believe this to be
      recrystallized hydroxyapatite. The purpose of this elemental analysis was to see
      if any of the silica fiber optic was melted and deposited as these globular
      structures on the canal wall. Two teeth were used. One was hand-instrumented with
      files and used as the control, the other was lased with a holmium:YAG laser. A
      245-micro low OH- fiber was used with a power setting of 0.75 W, 5 Hz, 94.2 J,
      and 1134 V to lase the root. The roots were microanalyzed for oxygen, phosphorus,
      silicon, nitrogen, hydrogen, calcium, and carbon. The percentages for all
      elements tested were the same for both teeth. Therefore, there was no silicon
      deposited onto the canal wall of the tooth that was lased. It is concluded that
      the low OH- silica fiber optic was not melted and deposited onto the dentinal
      canal wall.

PMID- 12814226
TI  - Cementoblasts maintain expression of osteocalcin in the presence of mineral
      trioxide aggregate.
AB  - This study investigated the effects of mineral trioxide aggregate on cementoblast
      growth and osteocalcin production in tissue culture. For cellular morphology
      studies, cementoblasts on mineral trioxide aggregate, IRM, and amalgam were
      incubated for 48 h then fixed for scanning electron microscopic analysis. For
      gene expression on mineral trioxide aggregate and IRM, reverse transcriptase
      polymerase chain reaction was performed using primer sets for glyceraldehyde-3
      phosphate dehydrogenase, type I collagen, alkaline phosphatase, osteocalcin, and
      bone sialoprotein after 3 and 5 days. In vitro matrix protein expression was
      evaluated by confocal microscopy for the presence of osteocalcin on MTA after 7
      and 12 days. Images were compared with controls to assess qualitative
      differences. Results suggest that mineral trioxide aggregate permits cementoblast
      attachment and growth and the production of mineralized matrix gene and protein
      expression. Our data indicates that mineral trioxide aggregate can be considered
      cementoconductive.

PMID- 12814227
TI  - In vitro infrared thermographic assessment of root surface temperature rises
      during thermafil retreatment using system B.
AB  - The purpose of this in vitro study was to measure the temperature rise on the
      outer root surface during retreatment of Thermafil using the System B HeatSource.
      Twenty extracted human maxillary premolars were filled with Thermafil with
      plastic carriers and divided into two groups of 10 teeth each. In group 1,
      Thermafil obturators were retrieved using System B HeatSource fitted with a
      medium plugger at a temperature of 225 degrees C. The plugger was placed first on
      the buccal, then on the lingual of the plastic carrier for 5 s each. This melted
      the gutta-percha and softened the plastic carrier. In group 2, Thermafil
      obturators were retrieved in the same manner except that the heated plugger was
      placed for 8 s. The temperature changes on the outer root surfaces were recorded
      using a thermal imaging camera. Thermafil retreatment in vitro using a System B
      HeatSource causes temperature rises ranging from 26.7 degrees C to 46.0 degrees
      C. This finding could possibly have implications for creating injury of the
      periodontal tissues.

PMID- 12814228
TI  - Antibacterial efficacy of a new chlorhexidine slow release device to disinfect
      dentinal tubules.
AB  - Dentinal tubules of 27 cylindrical bovine root specimens were infected with
      Enterococcus faecalis. In nine specimens, 5% chlorhexidine was placed in a slow
      release device (Activ Point) for 7 days, in another nine irrigation with 10 ml of
      0.2% chlorhexidine was used, and the remaining nine served as positive control.
      Powder dentin samples obtained from within the canal lumina using ISO 025 to 033
      burs were examined for the presence of vital bacteria by inoculating brain-heart
      infusion plates and counting colony forming units. Results were analyzed using
      analysis of variance and covariance with repeated measures. Heavy bacterial
      infection was observed at the layer close to the lumen in the control specimens,
      decreasing rapidly from layer to layer up to the deepest layer tested (400-500
      microm), which contained several hundred colony forming units. Viable bacteria in
      each layer of dentin were significantly reduced with chlorhexidine irrigation
      solution (p < 0.01) and were completely eliminated with the chlorhexidine slow
      release device (p < 0.01).

PMID- 12814229
TI  - Extraoral radiographic technique: an alternative approach.
AB  - The inability of certain patient populations to accept intraoral films and/or
      sensors can cause complications in the performance of endodontic therapy. An
      alternative technique (extraoral film placement) can be used to obtain clinically
      diagnostic radiographs. This article describes the alternative technique.

PMID- 12814230
TI  - Conventional and surgical treatment of a two-rooted maxillary central incisor.
AB  - Conventional and surgical endodontic management were performed on a two-rooted
      maxillary central incisor with a periapical lesion. Anatomical complexity of the
      tooth lead to perforation in the distal root during conventional treatment, thus
      a surgical approach was taken. A 4-month postoperative radiograph shows repair.

PMID- 12814231
TI  - In vivo validation of a one-dimensional finite-element method for predicting
      blood flow in cardiovascular bypass grafts.
AB  - Current practice in vascular surgery utilizes only diagnostic and empirical data
      to plan treatments and does not enable quantitative a priori prediction of the
      outcomes of interventions. We have previously described a new approach to
      vascular surgery planning based on solving the governing equations of blood flow
      in patient-specific models. A one-dimensional finite-element method was used to
      simulate blood flow in eight porcine thoraco-thoraco aortic bypass models. The
      predicted flow rate was compared to in vivo data obtained using cine phase
      contrast magnet resonance imaging. The mean absolute difference between computed
      and measured flow distribution in the stenosed aorta was found to be 4.2% with
      the maximum difference of 10.6% anda minimum difference of 0.4%. Furthermore, the
      sensitivity of the flow rate and distribution with respect to stenosis and branch
      losses were quantified.

PMID- 12814232
TI  - Conventional and reciprocal approaches to the inverse dipole localization problem
      of electroencephalography.
AB  - Forward transfer matrices relating dipole source to surface potentials can be
      determined via conventional or reciprocal approaches. In numerical simulations
      with a triangulated boundary-element three-concentric-spheres head model, we
      compare four inverse electroencephalogram (EEG) solutions: those obtained
      utilizing conventional or reciprocal forward transfer matrices, relating in each
      case source dipole components to potentials at either triangle centroids or
      triangle vertices. Single-dipole inverse solutions were obtained using simplex
      optimization with an additional position constraint limiting solution dipoles to
      within the brain region. Dipole localization errors are presented in all four
      cases, for varying dipole eccentricity and two different values of skull
      conductivity. Both conventional and reciprocal forward transfer matrices yielded
      inverse dipole solutions of comparable accuracy. Localization errors were low
      even for highly eccentric source dipoles on account of the nonlinear nature of
      the single-dipole solution and the position constraint. In the presence of
      Gaussian noise, both conventional and reciprocal approaches were also found to be
      equally robust to skull conductivity errors.

PMID- 12814233
TI  - Radio-wave exposure of the human head: analytical study based on a versatile
      eccentric spheres model including a brain core and a pair of eyeballs.
AB  - A versatile eccentric-spheres model of the human head is used in this paper to
      investigate radio-wave absorption. Numerical results, obtained by use of an exact
      analytical solution, are presented for the total, percentage, and gram-specific
      absorption. Interest is mainly in the brain and in the eyes of an adult or an
      infant head. Our model comprises a host sphere and several spherical inclusions,
      all concentrically stratified with respect to their own center. Any number of
      inclusions and any number of concentric layers for the host sphere and each one
      of the inclusions can be considered. Excitation is provided either by a plane
      wave or by a nearby electric dipole. The analytical solution is obtained by use
      of the indirect-mode matching method. The theory of this paper and the
      accompanying computer code constitute a versatile tool for analytical studies of
      cellular-phone interactions with the human head. Specific absorption rate maps in
      a horizontal cross section of the head model manifest the existence of hot spots
      in the eyes and near the center of the brain.

PMID- 12814234
TI  - ECG-based detection of body position changes in ischemia monitoring.
AB  - The purpose of this paper is to analyze and detect changes in body position (BPC)
      during electrocardiogram (ECG) recording. These changes are often manifested as
      shifts in the electrical axis and may be misclassified as ischemic changes during
      ambulatory monitoring. We investigate two ECG signal processing methods for
      detecting BPCs. Different schemes for feature extraction are used (spatial and
      scalar), while preprocessing, trend postprocessing and detection are identical.
      The spatial approach is based on VCG loop rotation angles and the scalar approach
      is based on the Karhunen-Loeve transform (KLT) coefficients. The methods are
      evaluated on two different databases: a database with annotated BPCs and the
      STAFF III database with recordings from rest and during angioplasty-induced
      ischemia but not including BPCs. The angle-based detector results in performance
      values of detection probability PD = 95%, false alarm probability PF = 3% in the
      BPC database and false alarm rate in the STAFF III database in control ECGs
      during rest RF(c) = 2 h(-1) (episodes per hour) and in ischemia recordings during
      angioplasty RF(a) = 7 h(-1), whereas the KLT-based detector produces values of PD
      = 89%, PF = 3%, RF(c) = 4 h(-1), and RF(a) = 11 h(-1), respectively. Including
      information on noise level in the detection process to reduce the number of false
      alarms, performance values of PD approximately equal to 90%, PF approximately
      equal to 1%, RF(c) approximately equal to 1 h(-1) and RF(a) approximately equal
      to 2 h(-1) are obtained with both methods. It is concluded that reliable
      detection of BPCs may be achieved using the ECG signal and should work in
      parallel to ischemia detectors.

PMID- 12814235
TI  - Automated processing of the single-lead electrocardiogram for the detection of
      obstructive sleep apnoea.
AB  - A method for the automatic processing of the electrocardiogram (ECG) for the
      detection of obstructive apnoea is presented. The method screens nighttime single
      lead ECG recordings for the presence of major sleep apnoea and provides a minute
      by-minute analysis of disordered breathing. A large independently validated
      database of 70 ECG recordings acquired from normal subjects and subjects with
      obstructive and mixed sleep apnoea, each of approximately eight hours in
      duration, was used throughout the study. Thirty-five of these recordings were
      used for training and 35 retained for independent testing. A wide variety of
      features based on heartbeat intervals and an ECG-derived respiratory signal were
      considered. Classifiers based on linear and quadratic discriminants were
      compared. Feature selection and regularization of classifier parameters were used
      to optimize classifier performance. Results show that the normal recordings could
      be separated from the apnoea recordings with a 100% success rate and a minute-by
      minute classification accuracy of over 90% is achievable.

PMID- 12814236
TI  - Multiwavelet grading of pathological images of prostate.
AB  - Histological grading of pathological images is used to determine level of
      malignancy of cancerous tissues. This is a very important task in prostate cancer
      prognosis, since it is used for treatment planning. If infection of cancer is not
      rejected by non-invasive diagnostic techniques like magnetic resonance imaging,
      computed tomography scan, and ultrasound, then biopsy specimens of tissue are
      tested. For prostate, biopsied tissue is stained by hematoxyline and eosine
      method and viewed by pathologists under a microscope to determine its
      histological grade. Human grading is very subjective due to interobserver and
      intraobserver variations and in some cases difficult and time-consuming. Thus, an
      automatic and repeatable technique is needed for grading. Gleason grading system
      is the most common method for histological grading of prostate tissue samples.
      According to this system, each cancerous specimen is assigned one of five grades.
      Although some automatic systems have been developed for analysis of pathological
      images, Gleason grading has not yet been automated; the goal of this research is
      to automate it. To this end, we calculate energy and entropy features of
      multiwavelet coefficients of the image. Then, we select most discriminative
      features by simulated annealing and use a k-nearest neighbor classifier to
      classify each image to appropriate grade (class). The leaving-one-out technique
      is used for error rate estimation. We also obtain the results using features
      extracted by wavelet packets and co-occurrence matrices and compare them with the
      multiwavelet method. Experimental results show the superiority of the
      multiwavelet transforms compared with other techniques. For multiwavelets,
      critically sampled preprocessing outperforms repeated-row preprocessing and has
      less sensitivity to noise for second level of decomposition. The first level of
      decomposition is very sensitive to noise and, thus, should not be used for
      feature extraction. The best multiwavelet method grades prostate pathological
      images correctly 97% of the time.

PMID- 12814237
TI  - Detecting objects in image sequences using rule-based control in an active
      contour model.
AB  - A method is presented for tracking object boundaries in sequential images using
      an active contour model, based on fuzzy reasoning rule-based control. Evolution
      of contour segments is controlled by separate processes based on whether the
      segment is judged to be inside, outside, or near the boundary of the object,
      leading to robust boundary detection.

PMID- 12814238
TI  - Ambulatory system for human motion analysis using a kinematic sensor: monitoring
      of daily physical activity in the elderly.
AB  - A new method of physical activity monitoring is presented, which is able to
      detect body postures (sitting, standing, and lying) and periods of walking in
      elderly persons using only one kinematic sensor attached to the chest. The
      wavelet transform, in conjunction with a simple kinematics model, was used to
      detect different postural transitions (PTs) and walking periods during daily
      physical activity. To evaluate the system, three studies were performed. The
      method was first tested on 11 community-dwelling elderly subjects in a gait
      laboratory where an optical motion system (Vicon) was used as a reference system.
      In the second study, the system was tested for classifying PTs (i.e., lying-to
      sitting, sitting-to-lying, and turning the body in bed) in 24 hospitalized
      elderly persons. Finally, in a third study monitoring was performed on nine
      elderly persons for 45-60 min during their daily physical activity. Moreover, the
      possibility-to-perform long-term monitoring over 12 h has been shown. The first
      study revealed a close concordance between the ambulatory and reference systems.
      Overall, subjects performed 349 PTs during this study. Compared with the
      reference system, the ambulatory system had an overall sensitivity of 99% for
      detection of the different PTs. Sensitivities and specificities were 93% and 82%
      in sit-to-stand, and 82% and 94% in stand-to-sit, respectively. In both first and
      second studies, the ambulatory system also showed a very high accuracy (> 99%) in
      identifying the 62 transfers or rolling out of bed, as well as 144 different
      posture changes to the back, ventral, right and left sides. Relatively high
      sensitivity (> 90%) was obtained for the classification of usual physical
      activities in the third study in comparison with visual observation.
      Sensitivities and specificities were, respectively, 90.2% and 93.4% in sitting,
      92.2% and 92.1% in "standing + walking," and, finally, 98.4% and 99.7% in lying.
      Overall detection errors (as percent of range) were 3.9% for "standing +
      walking," 4.1% for sitting, and 0.3% for lying. Finally, overall symmetric mean
      average errors were 12% for "standing + walking," 8.2% for sitting, and 1.3% for
      lying.

PMID- 12814239
TI  - Laser backscattering and transillumination imaging of human tissues and their
      equivalent phantoms.
AB  - Surface backscattering profiles from a human forearm and transmission profiles
      through a human thumb, of red and near-infrared lasers, were determined. For the
      preparation of tissue-equivalent phantoms, white paraffin wax mixed with various
      wax color pigments were used. The surface reflectance profiles of a human forearm
      were matched with that of the phantom by mixing color pigments in various
      proportions. The reconstructed surface reflectance image of the phantom prepared
      by this procedure was similar to that of the human forearm. The transmission
      tomogram of the human thumb was obtained in fan-beam configuration by a near
      infrared laser tomography system. Based on the horizontal scan of this tomogram,
      a two-layered phantom was made. The color composition of the phantom was so
      adjusted that its horizontal scan was matched with that of the thumb tomogram.
      The phantoms of complex tissues, prepared by this procedure, could be used for
      evaluation and calibration of new optical diagnostic imaging techniques.

PMID- 12814240
TI  - Computer-controlled mechanical simulation of the artificially ventilated human
      respiratory system.
AB  - A mechanical lung simulator can be used to simulate specific lung pathologies, to
      test lung-function equipment, and in instruction. A new approach to mechanical
      simulation of lung behavior is introduced that uses a computer-controlled active
      mechatronic system. The main advantage of this approach is that the static and
      dynamic properties of the simulator can easily be adjusted via the control
      software. A nonlinear single-compartment mathematical model of the artificially
      ventilated respiratory system has been derived and incorporated into the
      simulator control system. This model can capture both the static and dynamic
      compliance of the respiratory system as well as nonlinear flow-resistance
      properties. Parameters in this model can be estimated by using data from
      artificially ventilated patients. It is shown that the simulation model fits
      patient data well. This mathematical model of the respiratory system was then
      matched to a model of the available physical equipment (the simulator, actuators,
      and the interface electronics) in order to obtain the desired lung behavior. A
      significant time delay in the piston motion control loop has been identified,
      which can potentially cause oscillations or even instability for high compliance
      values. Therefore, a feedback controller based on the Smith-predictor scheme was
      developed to control the piston motion. The control system, implemented on a
      personal computer, also includes a user-friendly interface to allow easy
      parameter setting.

PMID- 12814241
TI  - Comparison of electric fields induced in humans and rodents by 60-Hz contact
      currents.
AB  - Contact currents flow when a conducting object such as an animal touches
      conductive surfaces at different potentials. This completes a path for current
      flow through the body. These currents provide an additional coupling mechanism
      between the human body and low-frequency external fields to that due to direct
      induction effects. Recent research indicates that childhood exposure to
      residential contact currents may play a role in explaining any possible
      association between residential magnetic fields and childhood leukemia. To verify
      this hypothesis, laboratory experiments with rodents are planned. Thus, it is
      important to understand the relationship between fields induced in rodents and
      humans. Results from numerical computations are reported here. They are based on
      high-resolution anatomically based inhomogeneous models of adult and child male
      humans and male and female rats and mice, for a variety of 60-Hz contact current
      scenarios. It is hoped that this work will aid in the design of experiments
      involving rodents and in the interpretation of results as applied to humans. It
      is found that for geometrically similar models, the induced electric-field scales
      in an anticipated inverse-square manner with the geometric scaling factor. For
      dissimilar models, scaling can provide a crude estimate for translating induced
      field results between species. However, numerical modeling provides the most
      suitable analysis tool for more accurate estimates.

PMID- 12814242
TI  - In vivo measurement of the brain and skull resistivities using an EIT-based
      method and realistic models for the head.
AB  - In vivo measurements of equivalent resistivities of skull (rho(skull)) and brain
      (rho(brain)) are performed for six subjects using an electric impedance
      tomography (EIT)-based method and realistic models for the head. The classical
      boundary element method (BEM) formulation for EIT is very time consuming.
      However, the application of the Sherman-Morrison formula reduces the computation
      time by a factor of 5. Using an optimal point distribution in the BEM model to
      optimize its accuracy, decreasing systematic errors of numerical origin, is
      important because cost functions are shallow. Results demonstrate that
      rho(skull)/rho(brain) is more likely to be within 20 and 50 rather than equal to
      the commonly accepted value of 80. The variation in rho(brain)(average = 301
      omega x cm, SD = 13%) and rho(skull)(average = 12230 omega x cm, SD = 18%) is
      decreased by half, when compared with the results using the sphere model, showing
      that the correction for geometry errors is essential to obtain realistic
      estimations. However, a factor of 2.4 may still exist between values of
      rho(skull)/rho(brain) corresponding to different subjects. Earlier results show
      the necessity of calibrating rho(brain) and rho(skull) by measuring them in vivo
      for each subject, in order to decrease errors associated with the
      electroencephalogram inverse problem. We show that the proposed method is suited
      to this goal.

PMID- 12814243
TI  - Assessment of myocardial lesion size during in vitro radio frequency catheter
      ablation.
AB  - We report our experience with a system that utilizes changes in several
      biophysical characteristics of cardiac tissue to determine lesion formation and
      to estimate lesion size both on and off-line in vitro during radio frequency (RF)
      energy delivery. We analyzed the reactive and resistive components of tissue
      impedance and tracked the change of phase angle during RF ablation. We correlated
      the amount of tissue damage with these and other biophysical parameters and
      compared them with off-line analysis. We found that there are irreversible
      changes in the reactive and resistive components of impedance that occurred
      during tissue ablation. The irreversible changes of these components are greater
      in magnitude, and correlate better with the size of lesions than that of
      impedance alone that is currently used. Numerically, the best single on-line and
      off-line correlation for combined perpendicular and parallel electrode
      orientation was with phase angle. On-line and off-line capacitance and
      susceptance correlations were essentially similar suggesting that they may be
      useful as lesion size predictors, given these parameter's persistent change
      without temperature sensitivity. This study indicates that it is technically
      feasible to assess lesion formation using biophysical parameters.

PMID- 12814244
TI  - Do the high-frequency indexes of HRV provide a faithful assessment of cardiac
      vagal tone? A critical theoretical evaluation.
AB  - When spectral analysis of the heart rate (HR) signal is performed, it is quite
      common to attribute the HF indexes of heart rate variability (HRV) to cardiac
      vagal control. The paradigm underlying this attribution states that changes in
      cardiac vagal outflow correspond to a proportional change in respiratory sinus
      arrhythmia (RSA). However, recent studies have demonstrated that variations in
      these indexes do not necessarily reflect proportional changes in vagal tone. The
      current study provides a theoretical evaluation of the relationship between mean
      HR, RSA, and cardiac vagal tone. This evaluation is based on a theoretical model,
      which quantifies the differential effects of vagal blockade by a competitive
      muscarinic antagonist on the HF indexes of HRV. The model relies on several
      assumptions that reflect the basic physiology of the sinoatrial (SA) node, as
      well as pharmacological relations that describe agonist/antagonist equilibrium at
      the SA receptors. The mathematical framework of this model is the integral-pulse
      frequency-modulation (IPFM) process, and its derivations lead to a specific
      expressions for the dependence of HF and mean HR on the level of vagal blockade.
      These expressions provide a new insight into the relationship between mean HR,
      RSA, and vagal tone, and explain conflicting experimental results previously
      published.

PMID- 12814245
TI  - Spatial relationships in electrostimulation: application to electromagnetic field
      standards.
AB  - Spatial relationships in electrostimulation are examined with a myelinated nerve
      model. Excitation thresholds are determined for: 1) terminated axon within a
      locally constant electric field; 2) bent axon within a locally constant field;
      and 3) a field of finite extent over the affected axon. For application to
      electromagnetic field standards, the minimum excitation threshold of the in situ
      electric field applies to a straight, terminated axon; a field measurement
      averaging distance of 5 mm is recommended.

PMID- 12814246
TI  - MEG source localization using an MLP with a distributed output representation.
AB  - We present a system that takes realistic magnetoencephalographic (MEG) signals
      and localizes a single dipole to reasonable accuracy in real time. At its heart
      is a multilayer perceptron (MLP) which takes the sensor measurements as inputs,
      uses one hidden layer, and generates as outputs the amplitudes of receptive
      fields holding a distributed representation of the dipole location. We trained
      this Soft-MLP on dipolar sources with real brain noise and converted the
      network's output into an explicit Cartesian coordinate representation of the
      dipole location using two different decoding strategies. The proposed Soft-MLPs
      are much more accurate than previous networks which output source locations in
      Cartesian coordinates. Hybrid Soft-MLP-start-LM systems, in which the Soft-MLP
      output initializes Levenberg-Marquardt, retained their accuracy of 0.28 cm with a
      decrease in computation time from 36 ms to 30 ms. We apply the Soft-MLP localizer
      to real MEG data separated by a blind source separation algorithm, and compare
      the Soft-MLP dipole locations to those of a conventional system.

PMID- 12814247
TI  - Independence of myoelectric control signals examined using a surface EMG model.
AB  - The detection volume of the surface electromyographic (EMG) signal was explored
      using a finite-element model, to examine the feasibility of obtaining independent
      myoelectric control signals from regions of reinnervated muscle. The selectivity
      of the surface EMG signal was observed to decrease with increasing subcutaneous
      fat thickness. The results confirm that reducing the interelectrode distance or
      using double-differential electrodes can increase surface EMG selectivity in an
      inhomogeneous volume conductor. More focal control signals can be obtained, at
      the expense of increased variability, by using the mean square value, rather than
      the root mean square or average rectified value.

PMID- 12814248
TI  - Characterization of 9L glioma model of the Wistar rat.
AB  - The aim of our study was to develop and characterize solid brain tumors in Wistar
      rats, which could be used in investigations concerning the molecular mechanisms
      that lay beneath the genesis of the gliomas as well as in the testing of curative
      potentials of various therapeutics. The tumors were induced by intracerebral
      inoculation of 9L glioma cells and characterized by morphometrical, histological
      and immunohistochemical analysis after 7, 14 and 21 postimplantation days.
      Immunohistochemical characterization included detection of the nuclear antigene
      Ki-67 as the proliferative cell marker, GFAP as a tracer of reactive gliosis
      surrounding the tumor mass, and CD4/CD8 and ED1 antigens, as markers of the
      immunological response. Our results showed that after 7 days all experimental
      animals developed solid, well-circumcised tumors, which were clearly separated
      from the surrounding brain tissue. Tumors showed progressive growth from the 7th
      to the 21st day despite the observed immunological response starting after 14
      days. Histologically tumors were hypercellular with neovascularization and
      necrosis. These results indicate that reproducible morphometric evaluation can be
      performed on 9L tumors growing in immunocompetent Wistar rats, enabling its use
      as an animal tumor model for the evaluation of various therapeutic approaches.

PMID- 12814249
TI  - Proliferative activity of microvascular cells in glioblastomas does not correlate
      with time to recurrence.
AB  - The time to recurrence operation (TR) is a good growth parameter, in particular
      for glioblastomas. Recently, we have shown that Ki-67 labeling index (LI) of
      tumor cells has a high inverse correlation with this time interval. In the
      current study, the LI of microvascular cells (MVC) was examined in the same
      glioblastoma cases. The LI of MVC of primary and recurrent tumors had no
      relationship and did not show any correlation to TR. The growth fraction of MVC
      was significantly lower than that of tumor cells. The MVC in glioblastomas seems
      to have chaotical proliferation properties without any link to the tumor growth
      potential. This observation may have implications for anti-angiogenic therapy.

PMID- 12814250
TI  - Concomitant differentiation and partial proteasome inhibition trigger apoptosis
      in neuroblastoma cells.
AB  - Proteasome activity is essential during cAMP-induced terminal differentiation of
      a murine neuroblastoma cell line (NBP2). However, the mechanisms through which
      proteasome affects NBP2 differentiation have not been characterized. We
      hypothesized that proteasome is required to implement the differentiation
      mediated effects on cell cycle, and its partial inhibition during differentiation
      may have adverse consequences. Here we show that partial inhibition of proteasome
      during cAMP-induced differentiation of NBP2 cells causes apoptosis. Whereas
      differentiation induced growth arrest at G1 phase, partial proteasome inhibition
      during differentiation resulted in the accumulation of cells at G2M phase. Cell
      cycle data correlated with the level of cyclin-dependent kinase inhibitors p21WAF
      and p27Kip1, and cyclin A. While the level of p21 and p27 increased, the level of
      cyclin A decreased upon differentiation. In contrast, cells treated with
      proteasome inhibitor in the presence of cAMP-inducing agents showed increased
      levels of p21 and cyclin A early in the course of differentiation. However, the
      level of p21 and p27, but not cyclin A, decreased later during concomitant
      differentiation and partial proteasome inhibition when cells were undergoing
      apoptosis. Our data suggest that differentiation-mediated growth arrest is
      dependent on the temporal activity of cell cycle proteins. Partial inhibition of
      proteasome interferes with differentiation events partly by stabilizing cell
      cycle proteins and this triggers apoptosis. Thus, differentiating drugs combined
      with partial proteasome inhibition may impart higher therapeutic efficacy than
      differentiating agents alone for the treatment of neuroblastoma tumors.

PMID- 12814251
TI  - Apoptotic DNA endonuclease (DNase-gamma) gene transfer induces cell death
      accompanying DNA fragmentation in human glioma cells.
AB  - AIMS: Both the genetic restoration of the apoptotic pathway and the introduction
      of proapoptotic molecules are now drawing attention. Concerning apoptosis of
      human glioma cells induced by human interferon-beta protein, we found that DNA
      endonuclease (DNase-gamma) acts as an executive molecule. The authors
      investigated whether gene transfer of this DNase-gamma exerts some therapeutic
      effects on human glioma cells. METHODS: We transduced U251SP, U251MG, and T98G
      human glioma cells with DNase-gamma gene via multilamellar cationic liposomes,
      monitored the growth of those cells, and carefully observed the cell-death
      pattern. RESULTS: DNase-gamma gene transfer resulted in an overexpression of
      DNase-gamma protein and induced DNA fragmentation in gene-transferred cells. The
      cytotoxic effect rose with multiple inoculations of the liposome, suggesting a
      relationship between its expression and the therapeutic effect. CONCLUSIONS:
      These results demonstrate that DNase-gamma gene transfer can induce apoptosis in
      human glioma cells, indicating its potential to become a future gene therapy
      strategy.

PMID- 12814252
TI  - Glioblastoma in kidney transplant recipients. Report of five cases.
AB  - Five patients who developed an intracranial glioblastoma after a kidney
      transplant are described. All patients underwent surgical removal of the lesion
      and eventually radiation therapy, but none of them is still alive at follow-up.
      The possibility of tumours occurring in transplant recipients is a recognised
      entity and several series have been reported. Nevertheless, little consideration
      has been paid to post-transplant gliomas and a precise evaluation of this risk is
      still lacking. Several hypotheses have been proposed to explain a possible link.
      One possible factor may be the immunosuppressive state of recipients as a result
      of post-transplant administration of immunosuppressive drugs, as it is known that
      gliomas have an higher incidence in HIV-infected patients. However, it is not yet
      clear whether immunosuppressive drugs function as a direct transforming factor.

PMID- 12814253
TI  - Chordoid glioma: report of a case with unusual histologic features,
      ultrastructural study and review of the literature.
AB  - Chordoid gliomas are an uncommon primary brain tumor with histologic features of
      a chordoma and immunolabeling for glial fibrillary acid protein. We report the
      32nd case with a review of the literature. The clinical, radiographic and
      pathologic features of the tumor are presented with new pathologic findings
      adding support that this lesion may be of ependymal origin. Treatment and long
      term outcome are limited but chordoid gliomas appear to be indolent lesions that
      may be cured with gross total resection.

PMID- 12814254
TI  - Combined modality therapy for poorly differentiated gliomas of the posterior
      fossa in children: a Children's Cancer Group report.
AB  - PURPOSE: To study the effectiveness of combined chemotherapy and radiotherapy for
      children with high-grade astrocytomas of the posterior fossa. PATIENTS AND
      METHODS: In the CCG-945 study, 250 patients were treated by members of the
      Children's Cancer Group (CCG). Sixteen children were randomly assigned to one of
      two chemotherapy regimens, vincristine, lomustine, and prednisone or '8-in-1',
      using the same involved-field irradiation in both. Six infants received 8-in-1
      chemotherapy before involved-field irradiation. All pathologic specimens had
      central review. RESULTS: Twenty-two patients with an institutional diagnosis high
      grade posterior fossa tumors received chemotherapy and/or irradiation. Fifteen
      were confirmed by central review to have high-grade gliomas. Overall survival for
      confirmed high-grade astrocytoma of the posterior fossa was approximately 36 +/-
      13% at 5 years for the children (n = 11) and 25 +/- 15% at 5 years for the
      infants (n = 4). CONCLUSIONS: Involved-field irradiation with chemotherapy
      appeared to prevent extraneural and subarachnoid metastases. We also confirmed
      the rarity of the tumor (6% of patients registered). Further Phase III trials are
      necessary to improve survival in this aggressive tumor.

PMID- 12814255
TI  - Psychometric- and quality-of-life assessment in long-term glioblastoma survivors.
AB  - BACKGROUND: Multimodal treatment of patients with glioblastoma multiforme (GBM)
      allows an increasing number of patients to survive beyond one year. On account of
      various neurological and psychophysiological impairments, however, these patients
      may not benefit in terms of quality of life (QOL). We evaluated the subjective
      QOL, clinical psychophysiological and cognitive functions in patients with GBM
      surviving 18 months after diagnosis. PATIENTS AND METHODS: Thirteen patients
      underwent psychophysiological and psychometric measurements for central-nervous
      activation, habituation of skin-conductance reaction, crystallized intelligence,
      verbal and psychovisual memory. QOL was assessed by the symptom check-list for
      somatization (SCS-Score). RESULTS: We found various impairments such as central
      nervous deactivation (n = 9) or high activation (n = 3), psychovegetative
      overexcitement (n = 3) or attenuation (n = 1), reduced verbal (n = 5) and/or
      psychovisual (n = 5) memory and loss in attention (n = 7) or concentration (n =
      5). Severe physical symptoms (grade 5) were fatigue, convulsion, headache, nausea
      and micturition difficulties. Eleven patients expressed high satisfaction with
      life in general, whereas only 4 were satisfied with their general state of
      health. All patients were independent and 8 patients returned to work.
      CONCLUSION: Despite various psychophysiological and cognitive impairments,
      subjective QOL appears mostly unaffected in this patient setting.

PMID- 12814256
TI  - Meningeal carcinomatosis as the first manifestation of a transitional cell
      carcinoma of the bladder.
AB  - Meningeal carcinomatosis (MC) as first manifestation of a transitional cell
      carcinoma (TCC) of the bladder is rare. We report a 66-year-old man, smoker, who
      presented with two episodes of secondarily generalized partial motor seizures.
      The routine blood test, brain computed tomography (CT) scan, brain magnetic
      resonance imaging and electroencephalogram were normal. Cerebral spinal fluid
      (CSF) revealed a significant pleocytosis and a morphology compatible with non
      differentiated non-small cell carcinoma. Broncofiberscopy, gastrofiberscopy,
      thoracicoabdominopelvic CT-scan and bone scintigraphy were normal but the urine
      cytology revealed malignant cells similar to those found in the CSF. TCC was
      diagnosed by cystoscopy and later necropsy confirmed the MC of this tumor. In
      this report we review the literature and analyze patient survival.

PMID- 12814257
TI  - Primary intramedullary spinal cord germinoma: case report.
AB  - We describe an 18-year-old male with an intramedullary spinal cord germinoma in
      whom the diagnosis was made two years after onset of a progressive myelopathy.
      Spinal cord germinomas are rare, most having been described in young Japanese
      adults. They often respond well to radiotherapy. A unique feature of this case
      was the prolonged time interval between onset of the patient's symptoms and
      ability to visualize the mass radiographically. A further interesting finding was
      the infiltrative nature of the tumor surrounding residual spinal cord neurons.

PMID- 12814258
TI  - Choroid plexus carcinoma presented with spinal dysfunction caused by a drop
      metastasis: a case report.
AB  - A 2-year-old girl demonstrating gait disturbance and dysuria was evaluated and
      showed two large remote tumors at the left lateral ventricle and lower spinal
      canal. Pathological analysis demonstrated both of the tumors to be choroid plexus
      carcinoma (CPC) with high MIB-1 labeling index. The enhanced mitotic propensity
      would have contributed to an early stage of drop metastasis from the primary site
      to the sacral sac and following accelerated formation of a longitudinal tumor,
      which had grown in the subarachnoid space conforming to the spinal canal and
      finally caused the presenting symptoms of spinal dysfunction. This report shows
      that CPC can develop exophytically in the subarachnoid space as well as in the
      ventricle simultaneously before appearance of clinical symptoms and confirms the
      importance of extensive neuroimaging in its evaluation.

PMID- 12814259
TI  - Phase II study of lonidamine and diazepam in the treatment of recurrent
      glioblastoma multiforme.
AB  - Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic
      endeavours, with low response rates and survival rarely exceeding 6 months. There
      are no standard chemotherapeutic regimens and new therapeutic approaches have to
      be found. We report an open-label, uncontrolled, multicentre phase II trial of
      lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a
      Karnofsky performance status > or = 70. The treatment regimen consisted of LND
      450 mg/day and diazepam 15 mg/day orally of every 28-day cycle until progression
      or unacceptable toxicity. Patients received a median of three cycles (range, 1
      12). No complete or partial response was observed. Therefore, according to the
      design of the study, no additional patients were enrolled and the trial was
      closed. Nevertheless, seven stabilizations (50%) were observed. Median time to
      progression was 8 weeks (range, 5-19 weeks). Median overall survival from
      recurrence was 15 weeks (range, 14-61 weeks). No grade 3-4 toxicity, except
      somnolence, was observed and there were no therapy-related deaths. Dose reduction
      for diazepam due to somnolence (grade III) was performed in 9 patients. The
      combination of LND and diazepam is well tolerated. LND and diazepam, acting on
      two distinct mitochondrial sites involved in cellular energy metabolism, may
      exert a cytostatic effect on tumour growth as shown by the high percentage of
      stable patients. The LND-diazepam at the used dosing schedule did not show a
      complete or partial response. LND plus diazepam may be interesting in the
      adjuvant setting or associated to chemotherapy to act on different targets and
      increase the therapeutic index.

PMID- 12814260
TI  - Long-term remission of primary central nervous system lymphoma by intensified
      methotrexate chemotherapy.
AB  - High-dose (1-3.5 g/m2) methotrexate (MTX) followed by whole-brain radiation
      therapy (WBRT) has consistently improved length of survival in primary central
      nervous system lymphoma (PCNSL), but the prognosis remains dismal. To optimize
      and enhance the dose intensity of MTX, we applied MTX at 8 g/m2 to 20 patients
      with PCNSL. In an effort to lower the risk of neurotoxic treatment sequelae, the
      WBRT dose was reduced to 30 Gy in cases of complete remission after MTX therapy.
      Further, omission of WBRT and administration of stereotactic radiotherapy (SRT)
      were undertaken in 3 older patients. The overall response rate to the MTX therapy
      was 83%. The median progression free survival (PFS) was 54 months with a median
      overall survival (OS) of 57 months. Achieving a complete response after MTX
      therapy was significantly associated with a longer PFS. Late neurotoxicity was
      encountered in 4 (50%) of 8 patients who were aged 60 years or older and received
      WBRT, but in none of 12 patients who were aged less than 60 years or avoided
      WBRT. All older patients who underwent SRT sustained complete remission without a
      dementing disease. Intensifying the MTX dosage to 8 g/m2 appears more promising
      in comparison to results reported with MTX doses of 1-3.5 g/m2. In younger
      patients, the establishment of complete remission by intensified MTX therapy and
      subsequent WBRT with a relatively lower dose could promise durable tumor
      remission with an acceptable neurotoxicity. In older patients, WBRT should be
      avoided to sustain a meaningful survival, and SRT may provide a valid strategy in
      terms of enhancing local disease control without undue risk.

PMID- 12814261
TI  - National Cancer Institute shows the way.

PMID- 12814262
TI  - Carbamylation of proteins in 2-D electrophoresis--myth or reality?
AB  - Carbamylation is widely quoted as being a problem in 2-D gel analysis and the
      associated sample preparation steps. This modification occurs when iso-cyanate, a
      urea break-down product, covalently modifies lysine residues, thus inducing a
      change in isoelectric point. Urea is used at up to 9 M concentrations in sample
      preparation and 2-D gels because of its ability to disrupt protein structure and
      effect denaturation without the need for ionic surfactants such as SDS. We have
      studied carbamylation using 7 M urea and 2 M thiourea, under a range of
      experimental temperatures to establish when, and if, it occurs and what can be
      done to minimize the modification. The actual time required for protein
      extraction from a tissue is usually short compared to the time required for
      procedures such as reduction and alkylation and IPG rehydration and focusing.
      Therefore, it is the temperature during these post-extraction procedures that is
      the most critical factor. Our experiments have shown that carbamylation does not
      occur during electrophoresis in the presence of urea, even with prolonged run
      times. However, under poorly controlled sample preparation and storage
      conditions, it can become a major event.

PMID- 12814263
TI  - Native disulfide bonds in plasma retinol-binding protein are not essential for
      all-trans-retinol-binding activity.
AB  - A human plasma retinol-binding protein (RBP) mutant, named RBP-S, has been
      designed and produced in which the six native cysteine residues, involved in the
      formation of three disulfide bonds, have been replaced with serine. A hexa
      histidine tag was also added to the C-terminus of RBP for ease of purification.
      The removal of the disulfide bonds led to a decrease in the affinity of RBP for
      all trans-retinol. Data indicates all-trans-retinol binds RBP and RBP-S with Kd =
      4 x 10(-8) M and 1 x 10(-7) M, respectively, at approximately 20 degrees C. RBP-S
      has reduced stability as compared to natural RBP below pH 8.0 and at room
      temperature. Circular dichroism in the far-UV shows that there is a relaxation of
      the RBP structure upon the removal of its disulfide bonds. Circular dichroism in
      the near-UV shows that in the absence of the disulfide bonds, the optical
      activity of RBP is higher in the 310-330 nm than in the 280-290 nm range. This
      work suggests that the three native disulfide bonds aid in the folding of RBP but
      are not essential to produce a soluble, active protein.

PMID- 12814264
TI  - Dynamic enhancements of sample loading and analyte concentration in capillary
      isoelectric focusing for proteome studies.
AB  - Capillary isoelectric focusing (CIEF) involves the use of the entire capillary
      filled with a mixture containing protein/peptide analytes and carrier ampholytes.
      Thus, the preparative capabilities of CIEF are inherently greater than most
      capillary-based electrokinetic separation techniques. To further increase sample
      loading and, therefore, the concentrations of focused analytes, a dynamic
      approach, which is based on electrokinetic injection of proteins/peptides from a
      solution reservoir, is demonstrated using a low p/ protein calibration kit and
      tryptic peptides from Saccharomyces cerevisiae. The proteins/peptides
      continuously migrate into the capillary and encounter a pH gradient established
      by carrier ampholytes originally present in the capillary for focusing and
      separation. Dynamic introduction and focusing in CIEF can be directly controlled
      by various electrokinetic conditions, including the injection time and the
      applied electric field strength. Differences in the sample loading are
      contributed by electrokinetic injection bias and are affected by the individual
      analyte's electrophoretic mobility. Depending on the mobilities of yeast
      peptides, the loading capacity of each peptide is measured to be around 8 to 45
      fold of that obtained in conventional CIEF. By comparing with the concentrations
      of dilute yeast peptides originally present in the reservoir, an overall
      concentration factor of 1400-7700 together with excellent separation resolution
      is achieved using dynamic introduction and focusing. This concentration effect is
      further illustrated by detecting 10 pg/microL of bradykinin peptide spiked in
      yeast protein digest using only ultraviolet absorption.

PMID- 12814265
TI  - Geometry of interaction of the histidine ring with other planar and basic
      residues.
AB  - Among the aromatic residues in protein structures, histidine (His) is unique, as
      it can exist in the neutral or positively charged form at the physiological pH.
      As such, it can interact with other aromatic residues as well as form hydrogen
      bonds with polar and charged (both negative and positive) residues. We have
      analyzed the geometry of interaction of His residues with nine other planar side
      chains containing aromatic (residues Phe, Tyr, Trp, and His), carboxylate (Asp
      and Glu), carboxamide (Asn and Gln) and guanidinium (Arg) groups in 432
      polypeptide chains. With the exception of the aspartic (Asp) and glutamic (Glu)
      acid side-chains, all other residues prefer to interact in a face-to-face or
      offset-face-stacked orientation with the His ring. Such a geometry is different
      from the edge-to-face relative orientation normally associated with the aromatic
      aromatic interaction. His-His pair prefers to interact in a face-to-face
      orientation; however, when both the residues bind the same metal ion, the
      interplanar angle is close to 90 degrees. The occurrence of different
      interactions (including the nonconventional N-H...pi and C-H...pi hydrogen bonds)
      have been correlated with the relative orientations between the interacting
      residues. Several structural motifs, mostly involved in binding metal ions, have
      been identified by considering the cases where His residues are in contact with
      four other planar moieties. About 10% of His residues used here are also found in
      sequence patterns in PROSITE database. There are examples of the amino end of the
      Lys side chain interacting with His residues in such a way that it is located on
      an arc around a ring nitrogen atom.

PMID- 12814266
TI  - Quantitative analysis of modified proteins by LC-MS/MS of peptides labeled with
      phenyl isocyanate.
AB  - Stable isotope tagging methods have enabled relative quantitation of proteins
      between samples in LC-MS/MS analyses. However, most such methods are not
      applicable to the differential quantitation of modified proteins because the
      isotope tagging reagents only react with certain peptides or because the reagents
      incorporate a mass increment that is too small to allow reliable quantitation on
      low resolution ion trap MS instruments. Here, we describe the use of d0- and d5
      phenyl isocyanate (PIC) as N-terminal reactive tags for essentially all peptides
      in proteolytic digests. PIC reacts quantitatively with peptide N-terminal amines
      within minutes at neutral pH and the PIC-labeled peptides undergo informative
      MS/MS fragmentation. Ratios of d0- and d5-PIC-labeled derivatives of several
      model peptides were linear across a 10000-fold range of peptide concentration
      ratios, thus indicating a wide dynamic range for quantitation. Application of PIC
      labeling enabled relative quantitation of several styrene oxide adducts of human
      hemoglobin in LC-MS/MS analyses. PIC labeling offers a versatile means of
      quantifying changes in modified or variant protein forms in paired samples.

PMID- 12814267
TI  - Structural and functional properties of IL-4delta2, an alternative splice variant
      of human IL-4.
AB  - Structural and functional properties of recombinant IL-4delta2, a naturally
      occurring splice variant of human IL-4 with a deletion of the loop region 22-37,
      have been analyzed. IL-4delta2 has alpha-helical structure and most likely
      preserves the "up-up-down-down" topology typical of the four-helix-bundle
      cytokines. IL-4delta2 interacts specifically with the alpha chain of IL-4R and
      competes effectively with IL-4 for the common binding sites. Thus, IL-4delta2 may
      act as a regulator of the cytokine net, being the natural antagonist of IL-4.

PMID- 12814268
TI  - Clinical and pharmacogenomic data mining: 1. Generalized theory of expected
      information and application to the development of tools.
AB  - New scientific problems, arising from the human genome project, are challenging
      the classical means of using statistics. Yet quantified knowledge in the form of
      rules and rule strengths based on real relationships in data, as opposed to
      expert opinion, is urgently required for researcher and physician decision
      support. The problem is that with many parameters, the space to be analyzed is
      highly dimensional. That is, the combinations of data to examine are subject to a
      combinatorial explosion as the number of possible events (entries, items, sub
      records) (a),(b),(c),... per record (a,b,c,..) increases, and hence much of the
      space is sparsely populated. These combinatorial considerations are particularly
      problematic for identifying those associations called "Unicorn Events" which
      occur significantly less than expected to the extent that they are never seen to
      be counted. To cope with the combinatorial explosion, a novel numerical "book
      keeping" approach is taken to generate information terms relating to the
      combinatorial subsets of events (a,b,c,..), and, most importantly, the zeta
      (Zeta) function is employed. The incomplete Zeta function zeta(s,n) with s = 1,
      in which frequencies of occurrence such as n = n(a,b,c,...) determine the range
      of summation n, is argued to be the natural choice of information function. It
      emerges from Bayesian integration, taken over the distribution of possible values
      of information measures for sparse and ample data alike. Expected mutual
      information l(a;b;c) in nats (i.e., natural units analogous to bits but based on
      the natural logarithm), such as is available to the observer, is measured as
      e.g., the difference zeta(s,o(a,b,c..)) - zeta(s,e(a,b,c..)) where o(a,b,c,..)
      and e(a,b,c,..) are, or relate to, the observed and expected frequencies of
      occurrence, respectively. For real values of s > 1 the qualitative impact of
      strongly (positively or negatively) ranked data is preserved despite several
      numerical approximations. As real s increases, and the output of the information
      functions converge into three values +1, 0, and -1 nats representing a trinary
      logic system. For quantitative data, a useful ad hoc method, to report sigma
      normalized covariations in an analogous manner to mutual information for
      significance comparison purposes, is demonstrated. Finally, the potential ability
      to make use of mutual information in a complex biomedical study, and to include
      Bayesian prior information derived from statistical, tabular, anecdotal, and
      expert opinion is briefly illustrated.

PMID- 12814269
TI  - Unseen proteome: mining below the tip of the iceberg to find low abundance and
      membrane proteins.
AB  - Abundant and hydrophilic nonmembrane proteins with isoelectric points below pH 8
      are the predominant proteins identified in most proteomics projects. In yeast,
      however, low-abundance proteins make up 80% of the predicted proteome,
      approximately 50% have pl's above pH 8 and 30% of the yeast ORFs are predicted to
      encode membrane proteins with at least 1 trans-membrane span. By applying highly
      solubilizing reagents and isoelectric fractionation to a membrane fraction of
      yeast we have a purified and identified 780 protein isoforms, representing 323
      gene products, including 28% low abundance proteins and 49% membrane or membrane
      associated proteins. More importantly, considering the frequency and importance
      of co- and post-translational modifications, the separation of protein isoforms
      is essential and two-dimensional electrophoresis remains the only technique which
      offers sufficient resolution to address this at a proteomic level.

PMID- 12814270
TI  - Self-assembling protein arrays using electronic semiconductor microchips and in
      vitro translation.
AB  - Protein arrays will greatly accelerate research and development in medical and
      biological sciences. We have used cell-free protein biosynthesis and a parallel
      immobilization strategy for producing protein biochips. We demonstrate a model
      two-protein microarray using luciferase and green fluorescent protein, both
      expressed in a cell-free system and specifically immobilized on CombiMatrix
      semiconductor oligonucleotide microarrays. This demonstration provides evidence
      for the appropriate folding, activity, robust presentation, and efficient
      flexible detection of proteins on the microscale.

PMID- 12814271
TI  - Evaluating immobilized metal affinity chromatography for the selection of
      histidine-containing peptides in comparative proteomics.
AB  - Agarose based immobilized metal affinity chromatography (IMAC) columns loaded
      with copper (II) were evaluated for the selection of histidine-containing
      peptides in comparative proteomics. Recovery, binding specificity, and
      reproducibility were investigated with model proteins. Cu(II)-IMAC was found to
      be highly selective for histidine containing peptides; moreover, a low degree of
      nonspecific selection was observed. Acylation of the amino-terminus of peptides
      with either succinic anhydride, N-acetoxysuccinamide, or [3-(2,5)-dioxopyrrolidin
      1-yloxycarbonyl)-propyl]-trimethylammonium (quaternary amine) reduced the number
      of histidine-containing peptides bound by the Cu(II)-IMAC columns. This provides
      an additional possibility for sample simplification in proteomic applications.
      The number of acylated peptides selected decreased in the order of quaternary
      amine > N-acetoxysuccinamide > succinic anhydride derivatization. Although the
      selection of N-terminally derivatized peptides is biased toward peptides that
      contain more than one histidine, it is not yet possible to predict selectivity.

PMID- 12814272
TI  - Use of the University of Rhode Island Change Assessment to measure motivational
      readiness to change in psychiatric and dually diagnosed individuals.
AB  - In this report, the original 4-factor structure of the University of Rhode Island
      Change Assessment (URICA; C. C. DiClemente & S. O. Hughes, 1990) was replicated,
      and the scale's internal consistency was found to be acceptable in a sample of
      120 psychiatric and dually diagnosed inpatient participants, who had participated
      in a randomized clinical trial comparing standard treatment (ST) and ST plus
      motivational interviewing. Contrary to the authors' hypotheses, participants
      classified as having low motivational readiness to change, based on their URICA
      scores, demonstrated greater treatment adherence than high-readiness
      participants, in that they attended a greater proportion of therapy groups while
      hospitalized (54% vs. 39%; p < .05) and clinic appointments during their 1st
      month postdischarge (77% vs. 53%; p < .05). Low-readiness participants were also
      more likely to attend all of their scheduled clinic appointments (26%) than were
      high-readiness participants (10%; p < .05).

PMID- 12814273
TI  - Factor structure of the SOCRATES in a clinical sample of adolescents.
AB  - This study investigated the Stages of Change Readiness and Treatment Eagerness
      Scale (SOCRATES; W. R. Miller & J. S. Tonigan, 1996) in adolescents presenting
      for treatment of alcohol use disorder (AUD). The participants were 80 males and
      43 females (mean age = 16.8 years) who presented for AUD treatment (95.1%
      outpatient, 4.9% inpatient). Participants completed assessments at baseline and 1
      year and provided information on alcohol use and related variables monthly
      between these 2 assessments. Principal-components and confirmatory factor
      analyses of the baseline SOCRATES identified 2 factors, Taking Steps and
      Recognition, which showed good internal consistency and concurrent and predictive
      evidence of validity. The results were interpreted as supporting the use of the
      SOCRATES with clinical samples of adolescents.

PMID- 12814274
TI  - Expectancy influences the operation of personality on behavior.
AB  - The authors investigated the moderating effect of expectancies on personality for
      2 different addictive behavior processes: (a) drinking and (b) binge eating and
      purging characteristic of bulimia nervosa. Study 1 found that positive
      expectancies for social facilitation from drinking moderated the effect of
      extraversion on drinking behavior among undergraduate men and women. Study 2
      found that the expectancy that eating will help manage negative affect moderated
      the effect of trait urgency on bulimic symptoms among undergraduate women. Thus,
      the relationships of the trait risk factors to these 2 addictive behaviors are
      stronger if one also holds certain expectancies for reinforcement from those
      behaviors.

PMID- 12814275
TI  - Peer and partner drinking and the transition to marriage: a longitudinal
      examination of selection and influence processes.
AB  - This study examined the longitudinal relationships among adult drinking, partner
      drinking, and peer drinking over the transition to marriage. Newlywed couples
      were assessed with respect to alcohol involvement, peer drinking, and risk
      factors and reassessed at their 1st anniversary. Husbands' premarital drinking
      was predictive of wives' drinking at the 1st anniversary, indicating partner
      influence. The results did not support a peer-influence hypothesis in that peer
      drinking at marriage was not predictive of husbands' or wives' drinking at the
      1st anniversary. There was evidence, however, for a peer-selection effect with
      husbands' premarital drinking predicting peer drinking for both husbands and
      wives. Wives' premarital drinking was unrelated to the subsequent drinking of
      their peers or their husbands' peers.

PMID- 12814276
TI  - Measuring alcohol expectancies with the implicit association test.
AB  - Researchers have relied primarily on self-report questionnaires to measure
      alcohol expectancies. These questionnaires assess explicit expectancies about
      alcohol but donot provide any measure of the implicit processes that might also
      play an important role in determining drinking. The implicit association test
      (IAT; A. G. Greenwald, D. E. McGhee, & L. K. Schwartz, 1998), a reaction time
      task, measures differential associations of 2 target concepts with an attribute.
      In this study, the IAT provided a measure of the strength of associations of
      alcohol concepts to positive or negative outcomes in memory. This implicit
      measure of alcohol expectancies successfully predicted alcohol use in 103
      undergraduates. The findings also supported the hypothesis that an implicit
      measure of expectancy can add to the predictive power of existing questionnaire
      based measures.

PMID- 12814277
TI  - Staying in treatment: how much difference is there from prison to prison?
AB  - This is the 1st study to examine the effects of individual- and program-level
      characteristics on treatment attrition within a prison-based setting. The sample
      of 1,446 men and women were from 19 programs. Differences were found in both
      individual- and program-level predictors of disciplinary discharges and dropouts.
      Dropouts were more likely to be women and enter treatment with lower levels of
      motivation. Individuals who were disciplinary discharges from treatment were more
      likely to be young, have a history of violence, and have a diagnosis of
      antisocial personality. Only 1 program factor--an emphasis on disciplinary
      discharge for violation of program rules--was associated with disciplinary
      discharge. The clinical implications of these findings are discussed.

PMID- 12814278
TI  - Social influences in motivated drinking among college students.
AB  - This study tested whether drinking motives mediate the relation between
      personality and alcohol use and whether these predictors affected drinking in
      these individuals' friends. College students and their friends participated in
      the study as dyads (n = 43 dyads, 86 participants). Each person completed surveys
      and a 28-day experience sampling protocol. Structural equation analyses found
      that (a) social motives mediated the relation between extraversion and alcohol
      outcomes, (b) coping motives mediated the relation between neuroticism and
      alcohol outcomes, and (c) enhancement motives mediated the relation between
      extraversion and alcohol outcomes. Moreover, young adults' alcohol use, but not
      their problem use, was influenced by their own drinking motives as well as the
      drinking motives of their best friends.

PMID- 12814279
TI  - Relation between childhood disruptive behavior disorders and substance use and
      dependence symptoms in young adulthood: individuals with symptoms of attention
      deficit/hyperactivity disorder and conduct disorder are uniquely at risk.
AB  - Most prior literature examining the relations among attention
      deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and substance use
      and abuse suggests that CD fully account for the ADHD-substance abuse relation.
      This study sought to test an alternate theory that individuals with symptoms of
      both ADHD and CD are at a special risk for substance abuse. Relations between
      childhood ADHD and CD symptoms, and young adult tobacco, alcohol, marijuana, and
      hard drug use and dependence symptoms, were examined in a sample of 481 young
      adults. ADHD and CD symptoms interacted to predict marijuana dependence symptoms
      and hard drug use and dependence symptoms, such that individuals with high levels
      of both ADHD and CD had the highest levels of these outcomes.

PMID- 12814280
TI  - Spiritual beliefs, world assumptions, and HIV risk behavior among heroin and
      cocaine users.
AB  - The relationship between spirituality and HIV risk behavior in a sample of 34
      inner-city cocaine-using methadone-maintained patients was examined. Spirituality
      was operationally defined in terms of "life meaningfulness" and included the
      Santa Clara Strength of Religious Faith (T. G. Plante & M. T. Boccaccini, 1997b)
      and the World Assumptions Scale (R. Janoff-Bulman, 1989; assessing benevolence,
      meaningfulness, and worthiness of the self). Hierarchical multiple regression
      analyses of self-reported drug- and sex-related risk behavior were conducted with
      sex and race entered as control variables. The full models accounted for 23% and
      42% of the variance in drug- and sex-related risk behavior, respectively.
      Strength of spiritual/religious faith (B = .37) and belief in a benevolent (beta
      = .50) and meaningful (beta = .46) world were independent predictors of sex
      related, but not drug-related, HIV preventive behavior.

PMID- 12814281
TI  - An alcohol expectancy-challenge prevention program for at-risk college women.
AB  - Alcohol expectancy-challenge programs are effective in changing expectancies and
      reducing drinking in college men (J. Darkes & M. S. Goldman, 1993, 1998);
      however, recent evidence suggests this protocol might not be effective for women
      (M. E. Dunn, C. Lau, & I. Y. Cruz, 2000). This study was designed to reevaluate
      the effectiveness of a social/sexual expectancy-challenge intervention in college
      women reporting moderate to heavy alcohol use. Forty-six undergraduate women were
      randomly assigned to the prevention or control condition. Participants reported
      alcohol expectancies at pre- and posttest and monitored their drinking patterns
      daily for 6 weeks. The program was effective in changing some expectancies but
      did not reduce drinking. This further confirms differences in the mechanisms by
      which expectancy-challenge programs function for men and women.

PMID- 12814282
TI  - Predicting postdischarge opiate abstinence from admission measures of motivation
      and confidence.
AB  - Admission scores from a model comprising 3 motivation factors concerning the
      cessation of heroin use and a confidence scale concerning postdischarge
      abstinence were tested for their ability to predict postdischarge outcomes in
      patients beginning inpatient opiate detoxification. Statistically significant
      prediction of abstinence from heroin 30 days after discharge and the number of
      heroin-free days in the 3 months following admission was based on the confidence
      scale and a factor concerned with externally imposed constraints on continued
      heroin use. The single-scale confidence measure made the largest contribution to
      each prediction, indicating that such scales may be potentially useful outcome
      predictors for postdischarge abstinence. External constraints on heroin use may
      not provide a basis for success in this treatment modality.

PMID- 12814283
TI  - In a secular spirit: strategies of Clinical Pastoral Education.
AB  - The Clinical Pastoral Education (CPE) model for the provision of spiritual care
      represents the emergence of a secularized professional practice from a
      religiously-based theological practice of chaplaincy. The transformation of
      hospital chaplaincy into "spiritual care services" is one means by which
      religious healthcare ministry negotiates modernity, in the particular forms of
      the secular realm of biomedicine and the pluralism of the contemporary United
      States healthcare marketplace. "Spiritual" is a label strategically deployed to
      extend the realm of relevance to any patient's "belief system:" regardless of his
      or her religious affiliation. "Theological" language is recast as a tool for
      conceptualizing the "spiritual lens:' Such moves transform chaplaincy from a
      peripheral service, applicable only to the few "religious" patients, into an
      integral element of patient care for all. Such a secularized professional
      practice is necessary to demonstrate the relevance and utility of spiritual care
      for all hospital patients in an era of cost-containment priorities and managed
      care economics.

PMID- 12814284
TI  - Betwixt and between: ritual and the management of an ultrasound waiting list.
AB  - Hospital waiting lists are a feature of publicly funded health services that
      results when demand appears to exceed supply. While much has been written about
      hospital waiting lists, little is known about the dynamics of diagnostic waiting
      lists, or more generally why hospital waiting lists behave in perverse and often
      counter-intuitive ways. This paper attempts to address this gap by applying a
      recent development in critical systems thinking called boundary critique to
      understand how a particular ultrasound waiting list was managed. A new waiting
      list metaphor based on waiting lists as ritual forms is proposed.

PMID- 12814285
TI  - Ethical issues in geriatric medicine: a unique problematic?
AB  - It is commonly believed that geriatric medicine generates a distinctive set of
      ethical problems. Implicated are such issues as resource allocation, competence
      and consent, advance directives, medical futility and deliberate death. It is
      also argued that it would be unjust to allow the elderly to compete with younger
      populations for expensive and scarce healthcare resources because the elderly
      "have already lived," and that treating them the same as these other populations
      would diminish the available resources unfairly, prolong a life of inevitably
      failing health and result in increased health care expenditures. In fact,
      however, this perception of ethical uniqueness is mistaken. Differences in
      medical conditions, demographics and aetiology should not be allowed to obscure
      the fact that ethical issues in geriatric medicine are essentially the same as
      those faced in any other area of health care, and that the solutions that are
      adopted in the geriatric context must be consistent with the ethical principles
      that are followed elsewhere. The paper argues that the root of the mistaken
      perception lies in the abandonment of the Hippocratic mandate of medicine and in
      an unreflective adherence to the belief that medical advances are inevitably
      beneficial. It is suggested that a return to patient-centred medicine and the use
      of ethics impact analyses before introducing medical advances may be ethically
      appropriate.

PMID- 12814286
TI  - The ground of dialogical bioethics.
AB  - Dialogical ethics are a procedural alternative to substantive ethics such as
      consequentialism, deontology, principlism, casuistry, virtue ethics and care
      ethics. Dialogical ethics are procedural in that they do not establish goods in
      advance, unlike substantive ethics, but rather determine goods through a
      procedure enacted by the actual parties involved (although some substantive
      notion of justice may still be required); and they are dialogical in that the
      procedure is that of dialogue, involving both empathic critical discussion and
      negotiation. A fundamental tenet of dialogical ethics may be the use of
      appropriate rules of order regulating dialogue among the parties involved. Some
      of the central characteristics of such rules of order are that they are
      reciprocally regulated by dialogue, that they override other ethical
      considerations, and that they institute empathic critical discussion and
      negotiation within the ethical dialogue. Dialogical bioethics are the application
      of dialogical ethics to ethical problems in medicine. The approach of dialogical
      bioethics has proven fruitful for resolving bioethical problems such as that of
      medical futility, where approaches of substantive ethics have reached an impasse.
      There is room for further study of special challengeswithin dialogical bioethics,
      such as the incompetence of some involved parties, conflicts of interests of
      third parties, and the cost-effectiveness of this ethical approach.

PMID- 12814288
TI  - Missing the mark: effects of time and causal attributions on goal revision in
      response to goal-performance discrepancies.
AB  - In an attempt to extend past goal setting research, the present study examined
      the influence of goal-performance discrepancies (GPDs), causal attributions, and
      temporal factors on the process of dynamic self-regulation. Goal revision
      processes were examined longitudinally in a sample of 100 varsity-level college
      track and field athletes over the course of an 8-week competitive season. The
      results indicate that an individual's GPD significantly predicted the amount of
      goal revision engaged in by the athletes, such that participants were more likely
      to lower their competition (proximal) and season (distal) goals when they failed
      to reach these goals and their respective GPDs were large. However, as
      hypothesized, this relationship was moderated by stability attributions and the
      temporal location of the individual with respect to the time period allotted for
      goal attainment. Implications for future research in the area of goal setting and
      dynamic self-regulation are discussed.

PMID- 12814287
TI  - E-medicine and health care consumers: recognizing current problems and possible
      resolutions for a safer environment.
AB  - Millions of Americans access the Internet for health information, which is
      changing the way patients seek information about, and often treat, certain
      medical conditions. It is estimated that there may be as many as 100,000 health
      related Web sites. The availability of so much health information permits
      consumers to assume more responsibility for their own health care. At the same
      time, it raises a number of issues that need to be addressed. The health
      information available to Internet users may be inaccurate or out-of-date.
      Potential conflicts of interest result from the blurring of the distinction
      between advertising and professional health information. Also, potential threats
      to privacy may result from data mining. Health care consumers need to be able to
      evaluate the quality of the information provided on the Internet. Various
      evaluative mechanisms such as codes of ethics, rating systems, and seals of
      approval have been developed to aid in this process. The effectiveness of these
      solutions is evaluated in this paper. Finally, the paper addresses the importance
      of including patients in developing standardized quality assurance systems for
      online health information.

PMID- 12814289
TI  - Backing up behaviors in teams: the role of personality and legitimacy of need.
AB  - In this article, the authors developed several hypotheses regarding both the main
      and interactive effects of 2 types of team inputs on backing up behaviors in
      teams: (a) team composition characteristics in terms of the personality of the
      members of the team and (b) team task characteristics in terms of the extent to
      which the nature of the task is one that legitimately calls for some members of
      the team to back up other members of the team. Results from a study of 71 4
      person teams performing a computerized tactical decision-making task suggest that
      the legitimacy of the need for back up has an important main effect on the extent
      to which team members provide assistance to and receive assistance from each
      other. In addition, the legitimacy of the need for back up also has important
      interactive effects with both the personality of the back up recipient and the
      personality of the back up providers on backing up behaviors in teams.

PMID- 12814290
TI  - Investigating the influence of organizational role on perceptions of risk in deep
      coal mines.
AB  - The authors replicated O. Ostberg's (1980) study of forestry workers using a
      range of personnel groups in coal mines. Findings demonstrate a high level of
      consensus between a range of personnel groups for a set of pictorially depicted
      behavioral risks, at the level of rank order, but significant differences in
      terms of relative magnitudes. Magnitudes of perceived risk were found to be
      greater for those closest to the point of hazard than for members of more
      geographically and experientially distal groups. Findings are interpreted with
      reference to experiential influences associated with organizational role.
      Revealed differences between personnel groups are explained in terms of cognitive
      availability, specifically effects associated with habituation and familiarity
      with risk, these sources of perceptual bias appearing to interact with
      organizational role.

PMID- 12814291
TI  - When the presence of creative coworkers is related to creativity: role of
      supervisor close monitoring, developmental feedback, and creative personality.
AB  - Study 1 was conducted to examine the contribution of the joint condition of
      supervisor close monitoring and the presence of creative coworkers to employees'
      creativity. In addition to replicating Study 1's results, Study 2 examined (a)
      the joint condition of supervisor developmental feedback and presence of creative
      coworkers and (b) whether creative personality moderated the contributions of the
      2 joint conditions. Converging results from the 2 field studies demonstrated that
      when creative coworkers were present, the less supervisors engaged in close
      monitoring, the more employees exhibited creativity. Study 2 also found that the
      contribution of this joint condition was stronger for employees with less
      creative personalities and that when creative coworkers were present, the more
      supervisors provided developmental feedback, the more employees exhibited
      creativity.

PMID- 12814292
TI  - The importance of normative beliefs to the self-prophecy effect.
AB  - Asking people to predict whether they will undertake a target behavior increases
      their probability of performing that behavior. Now referred to as the self
      prophecy effect, this phenomenon has been demonstrated across several contexts.
      Although theoretical explanations for the effect have been offered, empirical
      evidence for proposed accounts is sparse. The current research tests the
      theoretically relevant precondition for the effect that normative beliefs-
      evaluations of what is socially desirable or appropriate--underlie manifestation
      of the self-prophecy effect. Results of 2 experiments for different behaviors
      indicate that the act of making a prediction is most effective when normative
      beliefs are strong. Implications of these findings are discussed in relation to
      theoretical explanations for the effect and successful use of self-prophecy to
      promote socially desirable behaviors.

PMID- 12814293
TI  - Why managers should care about fairness: the effects of aggregate justice
      perceptions on organizational outcomes.
AB  - This work examines the aggregation of justice perceptions to the departmental
      level and the business-unit level, the impact of these aggregate perceptions on
      business-unit-level outcomes, and the usefulness of the distinction between
      procedural and interpersonal justice at different levels of analysis. Latent
      variables analyses of individual-level and department-level data from 4,539
      employees in 783 departments at 97 hotel properties showed that the 2 justice
      types exercise unique paths of impact on employees' organizational commitment and
      thus on turnover intentions and discretionary service behavior. Business-unit
      level analyses further demonstrate paths of association between aggregate justice
      perceptions, aggregate commitment levels, and the business-unit-level outcomes of
      employee turnover rates and customer satisfaction ratings.

PMID- 12814294
TI  - To justify or excuse?: A meta-analytic review of the effects of explanations.
AB  - The authors used R. Folger and R. Cropanzano's (1998, 2001) fairness theory to
      derive predictions about the effects of explanation provision and explanation
      adequacy on justice judgments and cooperation, retaliation, and withdrawal
      responses. The authors also used the theory to identify potential moderators of
      those effects, including the type of explanation (justification vs. excuse),
      outcome favorability, and study context. The authors' predictions were tested by
      using meta-analyses of 54 independent samples. The results showed strong effects
      of explanations on both the justice and response variables. Moreover,
      explanations were more beneficial when they took the form of excuses rather than
      justifications, when they were given after unfavorable outcomes, and when they
      were given in contexts with instrumental, relational, and moral implications.

PMID- 12814295
TI  - Peer responses to a team's weakest link: a test and extension of LePine and Van
      Dyne's model.
AB  - This article reports research intended to assess and extend a recent theory of
      peer responses to low-performing team members (J. A. LePine & L. Van Dyne,
      2001a). An instrument that assesses 4 types of peer responses to low performers
      (compensating for, training, motivating, and rejecting) was developed and then
      cross-validated in a subsequent study. Results of the study supported the
      validity of the peer responses measure and were generally consistent with the
      attributional theory of peer responses. Low-performer characteristics influenced
      the peer responses. These effects were mediated in part by peer attributions,
      affect, and cognitions, which explained variance in the peer responses over and
      above the variance explained by respondents' personality characteristics (i.e.,
      The Big Five).

PMID- 12814296
TI  - Predicting cross-cultural training performance: the validity of personality,
      cognitive ability, and dimensions measured by an assessment center and a behavior
      description interview.
AB  - This study examined the validity of a broad set of predictors for selecting
      European managers for a cross-cultural training program in Japan. The selection
      procedure assessed cognitive ability, personality, and dimensions measured by
      assessment center exercises and a behavior description interview. Results show
      that the factor Openness was significantly related to cross-cultural training
      performance, whereas cognitive ability was significantly correlated with language
      acquisition. The dimensions of adaptability, teamwork, and communication as
      measured by a group discussion exercise provided incremental variance in both
      criteria, beyond cognitive ability and personality. In general, these results are
      consistent with the literature on domestic selection, although there are some
      important differences.

PMID- 12814297
TI  - The effect of judgment type and confidence scale on confidence-accuracy
      calibration in face recognition.
AB  - Confidence-accuracy calibration was examined for both absolute (recognizing
      single faces as old or new) and relative (selecting which of pairs of faces is
      old) judgments, using both full- (0%-100%) and half-range (50%-100%) confidence
      scales. The half-range confidence scale demonstrated superior calibration to the
      full-range scale, for which a confidence-accuracy association was evident only
      for the upper half (i.e., 50%-100%) of the scale. Good calibration was observed
      for the absolute judgment conditions, but the relative judgment conditions
      evidenced marked underconfidence. Also, in the absolute judgment conditions, good
      calibration for positive recognition decisions and poorer calibration for
      negative decisions was observed. These results are discussed in the context of
      theories of confidence and accuracy in face recognition memory and also of
      eyewitness identification research.

PMID- 12814298
TI  - A personality trait-based interactionist model of job performance.
AB  - Evidence for situational specificity of personality-job performance relations
      calls for better understanding of how personality is expressed as valued work
      behavior. On the basis of an interactionist principle of trait activation (R. P.
      Tett & H. A. Guterman, 2000), a model is proposed that distinguishes among 5
      situational features relevant to trait expression (job demands, distracters,
      constraints, releasers, and facilitators), operating at task, social, and
      organizational levels. Trait-expressive work behavior is distinguished from
      (valued) job performance in clarifying the conditions favoring personality use in
      selection efforts. The model frames linkages between situational taxonomies
      (e.g., J. L. Holland's [1985] RIASEC model) and the Big Five and promotes useful
      discussion of critical issues, including situational specificity, personality
      oriented job analysis, team building, and work motivation.

PMID- 12814299
TI  - Recovery, work engagement, and proactive behavior: a new look at the interface
      between nonwork and work.
AB  - This study examined work-related outcomes of recovery during leisure time. A
      total of 147 employees completed a questionnaire and a daily survey over a period
      of 5 consecutive work days. Multilevel analyses showed that day-level recovery
      was positively related to day-level work engagement and day-level proactive
      behavior (personal initiative, pursuit of learning) during the subsequent work
      day. The data suggest considerable daily fluctuations in behavior and attitudes
      at work, with evidence that these are related to prior experience and opportunity
      for recovery in the nonwork domain.

PMID- 12814300
TI  - Work attitudes and decisions as a function of manager age and employee age.
AB  - Research has shown the importance of employee age relative to coworker age in
      determining attitudes, performance, and career-related opportunities. The authors
      used chronological and subjective measures of employee and manager age to
      determine whether employee age relative to the manager has an impact on these
      same outcome variables. One hundred eighty-five managers and 290 employees
      completed surveys. The strongest and most consistent age effects were observed
      for interactions between employee and manager chronological age. Both the
      magnitude and pattern of the employee-manager age interactions varied by self-
      and manager-rated outcome measures of work attitudes, performance and
      promotability assessments, and developmental experiences. Results are discussed
      in light of the relational demography and career timetable literatures.

PMID- 12814301
TI  - Reactions to merit pay increases: a longitudinal test of a signal sensitivity
      perspective.
AB  - The relationships among merit pay raises, trait positive affectivity (PA), and
      reactions to merit pay increases (pay attitudes and behavioral intentions) were
      explored in a longitudinal study of hospital employees. Drawing on signal
      sensitivity theory, the authors expected that PA would moderate the relationship
      between merit pay raise size and reactions to the increase such that pay raise
      size would be more strongly related to pay attitudes and behavioral intentions
      among those low in PA. Results strongly supported the predictions in the case of
      reactions to the raise amount (happiness and effort intentions) but not for pay
      level satisfaction. Implications of the results and directions for future
      research are identified.

PMID- 12814302
TI  - A field study of frame-of-reference effects on personality test validity.
AB  - As part of a test validation study at a major U.S.-based airline, the authors
      tested the effects of providing an "at work" frame-of-reference on the validity
      of the NEO Five-Factor Inventory among a sample of customer service supervisors
      (N = 206). Frame-of-reference moderated the validity of the Extraversion and
      Openness to Experience subscales after controlling for cognitive ability. In
      addition, the frame-of-reference personality test showed incremental validity
      over cognitive ability (deltaR2 = .16), but the standard personality test did not
      (deltaR2 = .05). The authors' discussion focuses on implications for personality
      theory and research and on implications for increasing the validity of
      personality tests in organizational settings.

PMID- 12814303
TI  - Management team learning orientation and business unit performance.
AB  - Although research has suggested that teams can differ in the extent to which they
      encourage proactive learning and competence development among their members (a
      team learning orientation), the performance consequences of these differences are
      not well understood. Drawing from research on goal orientation and team learning,
      this article suggests that, although a team learning orientation can encourage
      adaptive behaviors that lead to improved performance, it is also possible for
      teams to compromise performance in the near term by overemphasizing learning,
      particularly when they have been performing well. A test of this proposition in a
      sample of business unit management teams provides strong support. The results
      confirm that an appropriate emphasis on learning can have positive consequences
      for team effectiveness.

PMID- 12814304
TI  - Effects of multisource feedback and a feedback facilitator on the influence
      behavior of managers toward subordinates.
AB  - The authors compared a feedback workshop with both a no-feedback control group
      and a comparison group of managers who received a feedback report but no feedback
      workshop. The multisource feedback was based on ratings of a manager's influence
      behavior by subordinates, peers, and bosses. Managers in the feedback workshop
      increased their use of some core influence tactics with subordinates, whereas
      there was no change in behavior for the control group or for the comparison
      group. The feedback was perceived to be more useful by managers who received it
      in a workshop with a facilitator than by managers who received only a printed
      feedback report.

PMID- 12814305
TI  - Job-specific applicant pools and national norms for personality scales:
      implications for range-restriction corrections in validation research.
AB  - This article compares variability in national norms to variability in job
      specific applicant pools for personality scales. Across 23,231 job applicants for
      111 jobs, we found that job-specific applicant pools were slightly less variable
      than broad normative data (by about 4%) based on a national norm sample of 40,474
      job applicants. For some personality variables, the amount of variability
      reduction correlated with work characteristics as captured by the Data, People
      and Things scales of the Dictionary of Occupational Titles (US Department of
      Labor, 1977). Most correlations were small in magnitude. In general, the small
      reductions in job-specific applicant pool variability provide evidence that
      researchers' decisions to use manual norm group standard deviations in range
      restriction corrections has not appreciably inflated the personality-criterion
      relationships studied. Implications for attraction and gravitation to jobs are
      discussed.

PMID- 12814306
TI  - Tissue engineering--rewriting the rules of regeneration.

PMID- 12814307
TI  - Nonlinear finite element analysis of a splinted implant with various connectors
      and occlusal forces.
AB  - PURPOSE: The aim of this study was to analyze the biomechanics in an
      implant/tooth-supported system under different occlusal forces with rigid and
      nonrigid connectors by adopting a nonlinear finite element (FE) approach.
      MATERIALS AND METHODS: A model containing 1 Frialit-2 implant (placed in the
      second molar position) splinted to the mandibular second premolar was
      constructed. Nonlinear contact elements were used to simulate a realistic
      interface fixation between the implant body and abutment screw and the sliding
      keyway stress-breaker function. Stress distributions in the splinting system with
      rigid and nonrigid connectors were observed when vertical forces were applied to
      the tooth, pontic, implant abutment, or complete prosthesis in 10 simulated
      models. RESULTS: The displacement obtained from the natural tooth increased 11
      times than that of the implant, and the peak stress values within the implant
      system (sigmaI, max) increased significantly when vertical forces acted only on
      the premolar of a fixed prosthesis with a rigid connector. The sigmaI, max values
      seen in the splinting prosthesis were not significantly different when vertical
      forces (50 N) were applied to the pontic, molar (implant) only, or the entire
      prosthesis, respectively, regardless of whether rigid or nonrigid connectors were
      used. Moreover, the peak stress values in the implant system and prosthesis were
      significantly reduced in single- or multiple-contact situations once vertical
      forces on the pontic were decreased. DISCUSSION: The compensatory mechanism
      between the implant components and keyway sliding function of the implant/tooth
      supported prosthesis could be realistically simulated using nonlinear contact FE
      analysis. The nonrigid connector (keyway device) significantly exploited its
      function only when the splinting system received light occlusal forces.
      CONCLUSION: Minimization of the occlusal loading force on the pontic area through
      occlusal adjustment procedures to redistribute stress within the implant system
      in the maximum intercuspation position for an implant/tooth-supported prosthesis
      is recommended.

PMID- 12814308
TI  - Histologic evaluation of bone response to oxidized and turned titanium micro
      implants in human jawbone.
AB  - PURPOSE: To evaluate the human bone tissue response to 2 surfaces (oxidized or
      turned) on commercially available titanium implants. MATERIALS AND METHODS: Screw
      type turned (control) and oxidized (test) micro-implants were manufactured in the
      same manner as commercially available turned and oxidized (TiUnite, Branemark
      System) implants. The thickness of the oxide layer of the test implants was on
      average 10 microm, corresponding to the oxide thickness of the apical part of the
      TiUnite implant. Twenty patients received 1 test and 1 control micro-implant each
      during implant surgery. Before placement, the surface topography of the implants
      was characterized with an optical confocal laser profilometer. After a mean
      healing period of 6.6 months in the maxilla and 3.5 months in the mandible, the
      micro-implants and surrounding tissue were removed with a trephine bur.
      Histologic sections were produced, and the specimens were analyzed
      histomorphometrically. RESULTS: Surface roughness and enlargement were greater
      for the oxidized implants than for the turned implants. All micro-implants,
      except for 2 controls, were found to be clinically stable at the time of
      retrieval. Histomorphometric evaluation demonstrated significantly higher bone-to
      implant contact for the oxidized implants, whether placed in the maxilla or in
      the mandible. Significantly more bone was found inside the threaded area for the
      oxidized implants placed in the mandible and maxilla, but there was no difference
      between implants with regard to position (maxilla or mandible). DISCUSSION: The
      stronger bone response to the oxidized implants may have contributed to the fact
      that 2 control implants but no test implants were lost. The reason for these
      findings may depend on one or multiple differences of the surfaces between test
      and control implants: (1) the thicker oxide layer itself, (2) increased surface
      roughness, (3) different surface morphology in terms of porosity, or (4) change
      in crystal structure. CONCLUSION: The present histologic study in human jawbone
      demonstrated a significantly higher bone response for anodic oxidized titanium
      implants than for implants with a turned surface.

PMID- 12814309
TI  - A histomorphometric analysis of the effects of various surface treatment methods
      on osseointegration.
AB  - PURPOSE: One major factor in the success and biocompatibility of an implant is
      its surface properties. The purposes of this study were to analyze the surface
      characteristics of implants after blasting and thermal oxidation and to evaluate
      the bone response around these implants with histomorphometric analysis.
      MATERIALS AND METHODS: Threaded implants (3.75 mm in diameter, 8.0 mm in length)
      were manufactured by machining a commercially pure titanium (grade 2). A total of
      48 implants were evaluated with histomorphometric methods and included in the
      statistical analyses. Two different groups of samples were prepared according to
      the following procedures: Group 1 samples were blasted with 50-microm aluminum
      oxide (Al2O3) particles, and group 2 samples were blasted with 50-microm Al2O3,
      then thermally oxidized at 800 degrees C for 2 hours in a pure oxygen atmosphere.
      A noncontacting optical profilometer was used to measure the surface topography.
      The surface composition of the implants used and the oxide thickness were
      investigated with Rutherford backscattering spectrometry. RESULTS: The different
      preparations produced implant surfaces with essentially similar chemical
      composition, but with different oxide thickness and roughness. The morphologic
      evaluation of the bone formation revealed that: (1) the percentage of bone-to
      implant contact of the oxidized implants (33.3%) after 4 weeks was greater than
      that of the blasted group (23.1%); (2) the percentages of bone-to-implant contact
      after 12 weeks were not statistically significantly different between the groups;
      (3) the percentages of bone area inside the thread after 4 weeks and 12 weeks
      were not statistically significantly different between groups. DISCUSSION AND
      CONCLUSION: This investigation demonstrated the possibility that different
      surface treatments, such as blasting and oxidation, have an effect on the
      ingrowth of bone into the thread. However, the clinical implications of surface
      treatments on implants, and the exact mechanisms by which the surface properties
      of the implant affect the process of osseointegration, remain subjects for
      further study.

PMID- 12814310
TI  - Influence of implant design and bone quality on stress/strain distribution in
      bone around implants: a 3-dimensional finite element analysis.
AB  - PURPOSE: A 3-dimensional finite element analysis was performed to evaluate the
      influence of implant type and length, as well as that of bone quality, on the
      stress/strain in bone and implant. MATERIALS AND METHODS: Two types (screw and
      cylinder) and 4 lengths (9.2, 10.8, 12.4, and 14.0 mm) of titanium implants were
      buried in 4 types of bone modeled by varying the elastic modulus for cancellous
      bone. Axial and buccolingual forces were applied to the occlusal node at the
      center of the abutment. RESULTS: Regardless of load direction, maximum equivalent
      stress/strain in bone increased with a decrease in cancellous bone density. Under
      axial load, especially in the low-density bone models, maximum equivalent strain
      in cancellous bone was lower with the screw-type implant than with the cylinder
      type implant. It was also lower with the longer implants than with the shorter
      implants. Under buccolingual load, equivalent stress/strain was influenced mainly
      by bone density. DISCUSSION: This study confirms the importance of bone quality
      and its presurgical diagnosis for implant long-term prognosis. Implant length and
      type can also influence bone strain, especially in low-density bone. CONCLUSIONS:
      The results of this study suggest that cancellous bone of higher rather than
      lower density might ensure a better biomechanical environment for implants.
      Moreover, longer screw-type implants could be a better choice in a jaw with
      cancellous bone of low density.

PMID- 12814311
TI  - Effects of osteopromotive and anti-infective membranes on bone regeneration: an
      experimental study in rat mandibular defects.
AB  - PURPOSE: Reconstructive surgical treatment with osteopromotive membranes has
      become an integral part of implant dentistry. Nevertheless, there are still
      instances in which this technique alone is of limited or no benefit. The aim of
      the present study was to determine whether a combination of titanium membranes
      coated with transforming growth factor beta1 (TGF-beta1) and insulin-like growth
      factor I (IGF-I) is of value in the regeneration of so-called critical-size
      defects in the rat model. An analysis was made of whether or not locally
      administered antibiotics are deleterious to bone regeneration. MATERIALS AND
      METHODS: A total of 24 rats were included in the study and were divided into 4
      groups, each with 6 animals. Critical-size defects were created bilaterally and
      covered by titanium membranes coated with (1) polylactide, (2) polylactide and
      clindamycin, (3) polylactide and growth factors, or (4) polylactide, clindamycin,
      and growth factors. All 24 contralateral defects were covered by titanium
      membranes without any substrate (controls). Four weeks after treatment the
      animals were sacrificed. RESULTS: In groups 3 and 4, most defects showed thin but
      almost complete bridging of the defects with new bone formation. In particular,
      clindamycin had no inhibitory effect on the regeneration of bone. Nevertheless,
      after 28 days, there was no significant difference between the individual groups
      (including controls) with respect to the total amount of newly formed bone.
      DISCUSSION AND CONCLUSION: These results support the hypothesis that coating
      titanium membranes with TGF-beta1/IGF-I leads to almost complete bony bridging of
      critical-size defects without voluminous carrier materials. Moreover,
      simultaneous administration of clindamycin seems possible.

PMID- 12814312
TI  - Sinus augmentation bone grafts for the provision of dental implants: report of
      clinical outcome.
AB  - PURPOSE: The aim of this study was to report the outcome of sinus augmentation
      surgery with autogenous bone grafting in routine dental implant practice.
      MATERIALS AND METHODS: Twenty-seven sinus augmentation procedures were undertaken
      on 18 consecutive patients (mean age 43.7 years). The mandibular symphysis was
      used as the donor site for 11 patients. The iliac crest was used as a donor site
      for 7 bilateral cases. RESULTS: Six patients had implants placed at the time of
      grafting: the other 13 had a mean bone graft consolidation period of 24.7 weeks
      (range 9 to 39 weeks) before implants were placed. One patient who had a repeat
      procedure had both immediate and delayed techniques. A total of 79 Branemark
      System Mk II implants were placed in grafted bone (and 2 Mk IV implants were
      placed in a patient who had to have a repeat procedure) and proceeded to occlusal
      loading. After a mean follow-up period of 162 weeks (range 76 to 288 weeks), 16
      implants failed to integrate in grafted bone, representing an 80.25% survival
      rate. Fourteen patients proceeded to the planned prosthesis, 3 patients had a
      compromised treatment plan, and 1 patient was restored conventionally. This
      represents 94% of patients who were rehabilitated. DISCUSSION AND CONCLUSION: The
      sinus augmentation procedure using autogenous bone grafting can Increase bone
      volume to allow implant placement where there is insufficient bone. The survival
      of implants in the grafted bone, as measured by integration and successful
      loading, was reduced compared to implants placed in normal maxillary bone.
      Infection during the healing of the grafted site reduces the success of
      subsequent implant osseointegration.

PMID- 12814313
TI  - Microbiologic and radiographic analysis of ligature-induced peri-implantitis with
      different dental implant surfaces.
AB  - PURPOSE: The goal of this study was to evaluate microbiota and radiographic peri
      implant bone loss associated with ligature-induced peri-implantitis. MATERIALS
      AND METHODS: Thirty-six dental implants with 4 different surfaces (9 commercially
      pure titanium, 9 titanium plasma-sprayed, 9 hydroxyapatite, and 9 acid-etched)
      were placed in the edentulous mandibles of 6 dogs. After 3 months with optimal
      plaque control, abutment connection was performed. On days 0, 20, 40, and 60
      after placement of cotton ligatures, both microbiologic samples and periapical
      radiographs were obtained. The presence of Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, Prevotella intermedia/nigrescens, Campylobacter spp,
      Capnocytophaga spp, Fusobacterium spp, beta-hemolytic Streptococcus, and Candida
      spp were evaluated culturally. RESULTS: P intermedia/nigrescens was detected in
      13.89% of implants at baseline and 100% of implants at other periods. P
      gingivalis was not detected at baseline, but after 20 and 40 days it was detected
      in 33.34% of implants and at 60 days it was detected in 29.03% of dental
      implants. Fusobacterium spp was detected in all periods. Streptococci were
      detected in 16.67% of implants at baseline and in 83.34%, 72.22%, and 77.42% of
      implants at 20, 40, and 60 days, respectively. Campylobacter spp and Candida spp
      were detected in low proportions. The total viable count analysis showed no
      significant differences among surfaces (P = .831), although a significant
      difference was observed after ligature placement (P < .0014). However, there was
      no significant qualitative difference, in spite of the difference among the
      periods. The peri-implant bone loss was not significantly different between all
      the dental implant surfaces (P = .908). DISCUSSION AND CONCLUSIONS: These data
      suggest that with ligature-induced peri-implantitis, both time and periodontal
      pathogens affect all surfaces equally after 60 days.

PMID- 12814314
TI  - Immediate placement of implants into periodontally infected sites in dogs: a
      histomorphometric study of bone-implant contact.
AB  - PURPOSE: The placement of implants allows for re-establishment of function and
      esthetics following tooth loss. Immediate implant placement is a relatively
      recent procedure and has advantages, such as reduced number of surgical
      procedures, preservation of alveolar bone, reduction of cost and period of
      edentulism, and increased patient acceptance. However, there are some specific
      contraindications for the technique, such as the presence of an infection caused
      by periodontal disease and periapical lesions. The objective of this study was to
      evaluate the percentage of bone-implant contact of immediate implants placed in
      periodontally infected sites. MATERIALS AND METHODS: In the first phase,
      periodontitis was induced with ligatures in the mandibular premolars of 5 mongrel
      dogs, using the contralateral teeth as controls (received prophylaxis only).
      After 3 months, in the second phase of the study, 40 implants were placed in the
      alveoli of both experimental and control teeth. After a healing period of 12
      weeks, the animals were euthanized, and the hemimandibles were removed,
      dissected, fixed, and prepared for histomorphometric analysis of percentage of
      bone-implant contact. The Mann-Whitney test was used for statistical analysis.
      RESULTS: The results of the histomorphometric analysis indicated mean bone
      implant contact of 62.4% in the control group and 66.0% in the experimental
      group, a difference that was not statistically significant. DISCUSSION:
      Histomorphometric results revealed similar bone-implant contact in both groups,
      with no signs of infection. CONCLUSIONS: It was concluded that periodontally
      infected sites may not be a contraindication for immediate implantation in this
      animal model system, if adequate pre- and postoperative care is taken.

PMID- 12814315
TI  - Retrospective cohort study of the clinical performance of 1-stage dental
      implants.
AB  - PURPOSE: To evaluate long-term clinical performance of 1-stage dental implant
      prostheses at a single clinic, emphasizing clinical and demographic
      characteristics that affect implant survival. MATERIALS AND METHODS: Dental
      records of all 308 patients (674 implants) treated with 1-stage implants at Mayo
      Clinic from October 1993 through May 2000 were reviewed from implant placement to
      last visit. Exposure and outcome variables affecting performance were collected
      separately to control bias in the data collection process. Additional confounding
      factors (age and sex) were adjusted with the stratified Cox proportional hazards
      model. Implant survival was determined by means of a Kaplan-Meier survival
      estimate. The log-rank test was used to determine the role of clinical and
      demographic variables in implant survival. The relative risk associated with the
      possible effect of clinical and demographic variables on implant survival was
      estimated with the Cox proportional hazards model. RESULTS: The implant survival
      rate (n = 654 implants) was 97% (mean +/- SD follow-up, 21.0 +/- 18.8 months;
      range, 1 to 78 months). Performance bias was limited because nearly all patients
      were treated by 1 prosthodontist. Two implants failed after loading (6 and 9
      months). The incidence of complications was less than 4%. Among the implant
      failures, use of heterogeneous bone graft was associated with 4.8 times more
      failures than was use of autogenous bone graft (P = .04). After augmentation,
      delaying implant placement for 5 to 6 months resulted in 8.6 times more failures
      than the rate after earlier placement (P < .001). DISCUSSION: Retrospective
      review of the clinical performance of a 1-stage dental implant system yielded a
      97% survival rate, with no failures noted after 13 months. Prosthetic
      complications were low, especially for fixed implant prostheses. CONCLUSION:
      Clinical performance of 1-stage dental implant prostheses between 1993 and 2000
      demonstrated a high level of predictability.

PMID- 12814316
TI  - A comparison of hydroxyapatite (HA) -coated threaded, HA-coated cylindric, and
      titanium threaded endosseous dental implants.
AB  - PURPOSE: The purpose of this study was to compare the success of hydroxyapatite
      (HA) -coated and machined titanium (Ti) implants in a 5-year randomized,
      controlled clinical trial conducted at 2 centers. MATERIALS AND METHODS: Each of
      120 edentulous patients received HA-coated threaded, HA-coated cylindric, and
      machined Ti threaded implants in a randomized design using 5 or 6 implants.
      Digital radiographs allowed for yearly measurements of bone loss. Calibrated
      clinicians also measured mobility, Gingival Index, Plaque Index, probing depth,
      and recession. A Kaplan-Meier analysis was used to compare the proportion of
      ailing implants (defined as less than 2 mm of alveolar bone loss over 5 years)
      for each type of implant design. The criteria employed to assess implant outcome
      included the need for successful implants to lose less than 2 mm of bone support
      over the 5 years following placement of the prosthesis. RESULTS: This analysis
      revealed that 95.2% of machined Ti threaded implants and 97.92% of HA-coated
      threaded implants were successful, while 99.0% of HA-coated cylindric implants
      experienced less than 2 mm of bone loss (P < .06). DISCUSSION: All types of
      implants placed in this study had success rates above 95%. CONCLUSION: Over 5
      years, the success rate tended to favor HA-coated implants.

PMID- 12814317
TI  - Human recombinant tissue factor, platelet-rich plasma, and tetracycilne induce a
      high-quality human bone graft: a 5-year survey.
AB  - PURPOSE: To increase human bone graft regeneration and quality by the use of a
      mixture containing autologous ground calvarial bone, human recombinant tissue
      factor (rhTF), platelet-rich plasma (PRP), and tetracycline. MATERIALS AND
      METHODS: Maxillary sinus floor augmentation was performed on 18 patients by
      grafting a "bone paste" made of PRP (1.8 x 10(6) platelets/mm3 plasma), about 1
      microg rhTF, calvarial bone chips (2 to 5 mm in size), and tetracycline (10 to 30
      microg/mL preparation). Five to 6 months after the surgical phase and grafting a
      bone core was extracted for implant fixation, and the osseous core samples were
      analyzed microscopically. RESULTS: Histology revealed vascularized connective
      tissue rich in lamellar bone spicules containing osteocytes and surrounded by
      osteoblasts. The success rate of grafting was 90.3%. In 6-month postoperative
      blood samples, no residual coagulating disturbances could be found. DISCUSSION:
      The combination of calvarial bone chips, rhTF, PRP, and tetracycline results in a
      paste that is easy to handle, safe for patients, and possesses high bone
      regeneration capacity. CONCLUSION: The generalized use in implant dentistry, oral
      surgery, and orthopedics of such a protocol could facilitate the healing process
      as well as patient safety and surgeon comfort.

PMID- 12814318
TI  - A prospective multicenter clinical trial of 3i machined-surface implants: results
      after 6 years of follow-up.
AB  - PURPOSE: In this prospective multicenter clinical study, 1,179 3i standard
      threaded and self-tapping implants were followed for up to 6 years and monitored
      according to established success criteria. MATERIALS AND METHODS: A total of 493
      patients (240 men and 253 women) with a mean age of 45.1 years at implant surgery
      were enrolled at 6 research centers after being screened for exclusion criteria.
      Implants were placed according to a 2-stage surgical protocol with a minimum of 4
      months of submerged healing in the mandible and 6 months in the maxilla.
      Restorations included 633 prostheses, the majority of which were fixed partial
      dentures in the posterior mandible or maxilla or single-tooth replacements in the
      anterior maxilla. RESULTS: One hundred four implants (8.8%) did not meet success
      criteria and were designated as failures, and 222 implants (18.8%) were lost to
      follow-up. The cumulative success rate according to life table methods was 91.1%
      at 6 years. DISCUSSION: Sixty percent of the failed implants were short (< or =
      10 mm long), and their cumulative success rate as a group at 6 years was 89.0%,
      compared to 93.1% for longer implants (P < .05). Thirty-three percent of all
      failures were implants placed in the posterior maxilla, for a 5-year cumulative
      success rate of 87.4%. CONCLUSION: It appears that limited bone dimensions and
      poor-quality bone have an impact on the performance of these machined-surface
      implants.

PMID- 12814319
TI  - Clinical and radiologic evaluation of 2-stage IMZ implants placed in a single
      stage procedure: 2-year results of a prospective comparative study.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of using a 2-stage
      implant system in a single-stage procedure and to study the impact of the
      microgap between the implant and the abutment. MATERIALS AND METHODS: Sixty
      edentulous patients (Cawood class V or VI) participated in this study. After
      randomization, 20 patients received 2 IMZ implants placed in a single-stage
      procedure, 20 patients received 2 IMZ implants placed in the traditional 2-stage
      procedure, and 20 patients were treated with 2 ITI implants (single-stage
      procedure). The implants were placed in the canine area of the mandible. After 3
      months, mandibular overdentures were fabricated, supported by a bar-and-clip
      attachment. A standardized clinical and radiographic evaluation was performed
      immediately after prosthesis placement and after 12 and 24 months. RESULTS: One
      IMZ implant of the 1-stage group and 1 IMZ implant of the 2-stage group were lost
      after 6 and 12 months, respectively. Apart from several significant but
      clinically irrelevant differences, the 3 groups did not appear to differ markedly
      with regard to clinical parameters during the evaluation period. The mean bone
      loss within the first 2 years of functioning (1.1 mm IMZ 1-stage, 0.8 mm IMZ 2
      stage, 1.2 mm ITI) was comparable for the 3 groups. DISCUSSION AND CONCLUSIONS:
      The results of this study suggest that dental implants designed for a submerged
      implantation procedure can also be used in a single-stage procedure and may be as
      predictable as when the same implants used in a 2-stage procedure or as 1-stage
      implants. Placement of the microgap at the crestal level in 2-stage implants did
      not appear to have an adverse effect on the amount of peri-implant bone loss at 2
      years in this study population.

PMID- 12814320
TI  - Patient's informed consent prior to implant-prosthetic treatment: a retrospective
      analysis of expert opinions.
AB  - PURPOSE: The purpose of this retrospective analysis of expert opinions was to
      optimize the level of patient information prior to implant-prosthetic treatment.
      MATERIALS AND METHODS: Twenty-eight expert opinion reports on implant treatment
      cases compiled between 1996 and August 2001 were analyzed. RESULTS: Seventy-five
      percent of all cases subjected to expert opinion reports revealed generally
      inadequate patient information. Significant associations were found between
      diagnostic mistakes and a lack of or inadequate information about complications
      that occurred (P = .04). Inadequate prosthetic or periodontal pretreatment of the
      patient prior to implant treatment was associated with a lack of information
      concerning implant and periodontal maintenance (P = .023) as well as insufficient
      oral hygiene status (P = .001). DISCUSSION: In addition to a general lack of
      patient information, a lack of information about possible complications and
      inadequate information about treatment risks, treatment costs, and treatment
      alternatives were also found. CONCLUSION: Optimization of pretreatment
      information for patients, as well as improvement of communication with patients
      throughout the whole treatment and maintenance period, seem to be necessary.

PMID- 12814321
TI  - Vertical ridge augmentation using xenogenic material supported by a configured
      titanium mesh: clinicohistopathologic and histochemical study.
AB  - PURPOSE: The aim of this study was to evaluate the capability of a configured
      titanium mesh (CTM) to serve as a mechanical and biologic device for restoring a
      vertically defected/resorbed alveolar ridge. MATERIALS AND METHODS: The study
      comprised 10 severely resorbed sites in 10 patients. Pre- and post-operative
      ridge measurements were taken with reference to the neighboring teeth and
      supporting screw head base of the CTM. Bovine bone mineral served as the
      augmentation filler material. The metal mesh was removed after 9 months.
      Subsequently, root-form, screw-type implants were placed. During the implant
      placement phase, cylindric bone samples were retrieved from the augmented area
      for histopathologic and histochemical examination. RESULTS: Upon soft tissue
      reflection and before augmentation, defect height, as recorded by a periodontal
      probe along the main threads exposed on the support screw, was between 5 and 8 mm
      (average 6.4 mm; SD +/- 1.17). At 9 months after augmentation, during the implant
      placement phase, the defect height was between 0 and 2 mm (average 1.2 mm; SD +/-
      0.63). Differences were statistically significant (P < .001). Bone height gain
      was between 4 and 6 mm (average 5.2 mm, SD +/- 0.79), which gave an average bone
      fill of 81.2% (SD +/- 7.98). Polarizing microscopic examination of sections
      stained with Picrosirius red showed a gradual increase in new lamellar bone from
      coronal to apical cuts, reaching the highest area percentage in the deep apical
      zone. DISCUSSION: At 9 months postaugmentation using the CTM surgical technique,
      the quality and quantity of the newly established hard tissue appeared to be
      different in the coronal versus apical areas of the restored alveolar ridge.
      CONCLUSION: Although at 9 months postoperatively, the augmented alveolar ridge
      had different bone content, clinicohistochemical results demonstrated that this
      surgical technique could be a successful and predictable procedure for rebuilding
      a resorbed/defected ridge to accommodate endosseous implants.

PMID- 12814322
TI  - Posterior mandibular residual ridge resorption in patients with conventional
      dentures and implant overdentures.
AB  - PURPOSE: This study investigated the effects of certain systemic and local
      factors on resorption of the posterior mandibular residual ridge under
      conventional dentures and overdentures supported by 2 implants. MATERIALS AND
      METHODS: Proportional area measurements of the posterior mandible were made on
      rotational tomograms taken immediately before and 5 years after treatment. The
      area was bounded by a line joining gonion to the lowest point of the mental
      foramen and the crest of the residual ridge and was expressed as a proportion of
      an area that was not dependent on the ridge. The use of proportions rather than
      actual measurements minimized errors related to magnification and distortion.
      RESULTS: The estimated average reduction in height was 1.25 mm in 5 years (1.63
      mm for conventional denture groups and 0.69 mm for implant overdenture groups,
      ie, almost 1 mm less in the overdenture group). DISCUSSION AND CONCLUSION: Female
      gender was a risk factor for greater resorption. Other factors, such as the
      number of years a patient had been edentulous, initial height of the mandible,
      and the number of dentures used, failed to show an association with resorption of
      the residual posterior mandibular ridge, while the statistically significant
      effect of age was unlikely to be clinically significant.

PMID- 12814323
TI  - Prospects and limits of pharmacogenetics: the thiopurine methyl transferase
      (TPMT) experience.
AB  - Thiopurine drug metabolism is a quintessential case of pharmacogenetics. A wealth
      of experimental and clinical data on polymorphisms in the thiopurine metabolizing
      enzyme thiopurine methyl transferase (TPMT) has been generated in the past
      decade. Pharmacogenetic testing prior to thiopurine treatment is already being
      practiced to some extent in the clinical context, and it is likely that it will
      be among the first pharmacogenetic tests applied on a regular basis. We analyzed
      the published TPMT data and identified some lessons to be learned for the future
      implementation of pharmacogenetics for thiopurines as well as in other fields.
      These include the need for comprehensive and unbiased data on allele frequencies
      relevant to a broad range of populations worldwide. The nature and frequency of
      TPMT gene polymorphisms in some ethnic groups is still a matter of speculation,
      as the vast majority of studies on TPMT allele distribution are limited to only a
      small subset of alleles and populations. Secondly, an appreciation of the limits
      of pharmacogenetics is warranted, as pharmacogenetic testing can help in avoiding
      some, but by far not all adverse effects of drug therapy. An analysis of six
      clinical studies correlating adverse thiopurine effects and TPMT genotype
      revealed that an average of 78% of adverse drug reactions were not associated
      with TPMT polymorphisms. Pharmacogenetic testing will thus not eliminate the need
      for careful clinical monitoring of adverse drug reactions. Finally, a careful
      approach toward dose increases for patients with high enzyme activity is
      necessary, as TPMT-mediated methylation of thiopurines generates a possibly
      hepatotoxic byproduct.

PMID- 12814324
TI  - Cancer drugs, genetic variation and the glutathione-S-transferase gene family.
AB  - The glutathione-S-transferase (GST) super family comprises multiple isozymes
      (Alpha, Mu, Pi, Omega, Theta, and Zeta) with compelling evidence of functional
      polymorphic variation. Over the last two decades, a significant body of data has
      accumulated linking aberrant expression of GST isozymes with the development and
      expression of resistance to cancer drugs. Clinical correlation studies show that
      genetic differences within the human GST isozymes may play a role in cancer
      susceptibility and treatment. The initial confusion was presented by the fact
      that not all drugs used to select for resistance were substrates for thioether
      bond catalysis by GSTs. However, recent evidence that certain GST isozymes
      possess the capacity to regulate mitogen activated protein kinases presents an
      alternative explanation. This dual functionality has contributed to the recent
      efforts to target GSTs with novel small molecule therapeutics. While the ultimate
      success of these attempts remains to be shown, at least one drug is in late-stage
      clinical testing. In addition, the concept of designing new drugs that might
      interfere with protein:protein interactions between GSTs and regulatory kinases
      provides a novel approach to identify new targets in the search for cancer
      therapeutics.

PMID- 12814326
TI  - Approaches to identifying genetic predictors of clinical outcome in rheumatoid
      arthritis.
AB  - Predicting which patients with rheumatoid arthritis (RA), at presentation, are
      likely to suffer a severe disease course based on genotype data would be a major
      clinical advance. It would ensure that patients at highest risk of a severe
      outcome could be targeted with early aggressive therapies. With a better
      understanding of interactions between genotype and drug response it would be
      possible to prescribe treatments most likely to be efficacious and safe for
      specific patient subgroups. While a clear genetic component has been demonstrated
      in RA severity, the identification of genetic factors poses a challenge to
      researchers in the field. Initiatives such as the SNP Consortium and advances in
      genotyping technology have facilitated the investigation of genetic factors in
      both disease susceptibility and severity. However, several other factors, such as
      the availability of suitable longitudinal cohorts, definition of outcome
      measures, study design, selection of genetic markers, and statistical power, will
      all contribute to the likely success of genetic studies. Several strategies that
      have been applied in the pursuit of genetic predictors of clinical outcome in RA.
      While some encouraging results have been generated, it has so far been difficult
      to quantify the predictive value of genetic markers and extrapolate the results
      from genetic studies to clinic patients. Establishing high quality prospective
      inception cohorts, a more systemic approach to defining suitable outcome
      measures, and understanding the effects of treatment, will be critical to the
      eventual identification of good predictive genetic markers.

PMID- 12814325
TI  - Mutations in cardiac sodium channels: clinical implications.
AB  - Voltage-gated sodium channels (VGSCs) are critical transmembrane proteins
      responsible for the rapid action potential upstroke in most excitable cells.
      Recently discovered mutations in VGSCs, which underlie idiopathic clinical
      disease, have emphasized the importance of these channels in tissues such as
      skeletal muscle, nervous system, and myocardium. Mutations in the gene encoding
      the cardiac sodium channel isoform (SCN5A) have been linked to at least three
      abnormal phenotypes: variant 3 of the Long QT syndrome (LQT-3); Brugada's
      syndrome (BrS); and isolated cardiac conduction disease (ICCD). Mutations in
      SCN5A manifest as one or more of these clinical phenotypes - the precise
      distinction between these diseases is increasingly subtle. Clinical management of
      LQT-3 and diagnosis of BrS with the local anesthetic flecainide has proven
      promising. Channels associated with LQT-3 (D1790G) and BrS (Y1795H) both show
      more sensitivity to flecainide than wild-type (WT) channels, while lidocaine
      sensitivity is unchanged. One plausible explanation for differential drug
      sensitivity is that mutant channels may allow more access to a receptor site
      compared with WT through altered protein allosteric changes during an action
      potential. The high affinity binding site for local anesthetic block has been
      identified in the pore region of the channel. This region is not water accessible
      during the closed state, thus requiring channel opening for charged drug
      (flecainide and mexiletine) access and block. Channel mutations which disrupt
      inactivation biophysics lead to increased drug binding by altering the time the
      binding site is accessible during an action potential. Neutral drugs (lidocaine)
      which are not dependent on channel opening for binding site access will not be
      sensitive to mutations that alter channel inactivation properties. Interestingly
      another LQT-3 mutant (Y1795C) shows no change in flecainide sensitivity,
      suggesting that although drug effects of SCN5A mutations cross disease
      boundaries, clinical management with flecainide will be beneficial to patients in
      a mutation-specific manner.

PMID- 12814327
TI  - Uncovering the genetics of systemic lupus erythematosus: implications for
      therapy.
AB  - Although it is well known that genetic factors contribute significantly to the
      expression of systemic lupus erythematosus (SLE) it was only recently realized,
      through genome-wide searches, that the number of involved genes is rather large.
      The published information hints at two facts: first, the number of genomic loci
      identified in various diverse cohorts is large and not necessarily overlapping;
      and second, certain loci may be preferentially linked with specific clinical
      manifestations. The latter may ultimately lead to a better understanding of the
      nature of the clinical entity that we know as SLE, and identification of groups
      of patients prone to respond better to treatment or to develop significant
      adverse effects. Advances attained regarding the nature of the biochemical and
      molecular defects that underwrite the aberrant function of immune cells parallel
      the progress made on the genetic origin of the disease. The genetic links need to
      be connected with aberrant function of their products to validate their
      significance. It is expected that correction of molecular aberrations either
      medicinally or by gene therapy will provide the needed specific treatment for
      patients with SLE.

PMID- 12814328
TI  - Commercial biobanks and genetic research: ethical and legal issues.
AB  - Human biological material is recognized as an important tool in research, and the
      demand for collections that combine samples and data is increasing. For-profit
      companies have assumed a leading role in assembling and managing these
      collections. The emergence of commercial biobanks has raised significant ethical
      and legal issues. The growing awareness of the importance of human biological
      material in research has been accompanied by a growing awareness of the
      deficiencies of existing archives of tissue. Commercial biobanks are attempting
      to position themselves as a, if not the, solution to problems that include a lack
      of public trust in researchers and lack of financial resources to support the
      prospective creation of collections that meet the highest scientific and ethical
      standards in the non-profit sector. Broad social and policy questions surrounding
      the operation of commercial biobanks have been raised however. International
      documents, in particular, suggest discomfort with the idea of gain from the mere
      transfer or exchange of human genetic material and information. Commercial
      involvement in the development of useful products from tissue is generally not
      condemned, so long as there is attention to scientific and social norms. Views on
      the acceptability of commercial biobanks vary. Specific issues that arise when
      commercial biobanks are permitted--in the areas of consent, recruitment,
      confidentiality, and accountability--are also relevant to the operation of public
      and private, non-profit biobanks. Although many uncertainties remain, consensus
      seems to be forming on a number of issues. For example, there appears to be
      agreement that blanket consent to future unspecified research uses, with no
      conditions, is unacceptable. Indeed, many of the leading commercial biobanks have
      been attentive to concerns about consent, recruitment, and confidentiality.
      Unfortunately, the binding nature of assurances in these areas is unclear,
      especially given the risk of insolvency. Hence, accountability may be the most
      important area of concern in relation to commercial biobanks. A few countries
      have enacted general legislation providing for comprehensive regulation of
      biobanks, for example, through licensure. Efforts to achieve harmonization of
      standards at the international level, and cautions against an approach that
      focuses on biobanking for genetic research alone, are to be applauded.

PMID- 12814329
TI  - Mass psychogenic illness after vaccination.
AB  - When vaccines are administered to groups, the physical reactions of the
      recipients may be similar, causing a form of mass reaction, the mechanism for
      which is the same as that for mass reactions from other causes. These phenomena
      have been categorised as mass psychogenic illness (MPI), and have been defined as
      the collective occurrence of a constellation of symptoms suggestive of organic
      illness but without an identified cause in a group of people with shared beliefs
      about the cause of the symptom(s). A review of the literature shows that such
      outbreaks have been reported in differing cultural and environmental settings
      including developing and industrialised countries, in the work place, on public
      transport, in schools, and the military. The perceived threats have been against
      agents such as food poisoning, fire and toxic gases. Whatever the place or
      perceived threat, the response seems to be similar. The symptoms generally
      included headache, dizziness, weakness, and loss of consciousness. Once under
      way, MPIs are not easy to stop. Incidents reported in the literature show that
      they can quickly gather momentum and can be amplified by the press who
      disseminate information rapidly, escalating the events. Management of such mass
      events can be extremely difficult. Should the public health official in charge
      continue to try and determine the cause, or should this person call off the
      entire investigation? It is suggested here that once vaccines are identified as a
      probable cause of the phenomenon, a dismissive approach may actually be harmful.
      Unless the spokesperson has already earned a high level of trust, the public are
      not likely to be convinced easily that nothing was wrong with the vaccine until
      it has been tested. An increased awareness of MPIs on the part of organisers of
      future mass vaccination campaigns seems appropriate. Immunisation managers should
      be aware that mass immunisation campaigns could generate such mass reactions. It
      is therefore essential that surveillance/reporting systems for reporting adverse
      events be improved before such campaigns. A mass campaign using a smallpox
      vaccine should be accompanied by a surveillance system capable of distinguishing
      between multiple cases of conventionally understood vaccine reactions and
      outbreaks of mass psychogenic illness.

PMID- 12814330
TI  - Hydroxyurea in the treatment of HIV infection: clinical efficacy and safety
      concerns.
AB  - Data from basic science and clinical studies suggest that hydroxyurea
      (hydroxycarbamide)-based regimens are effective treatment options for patients
      with HIV at various stages of disease. In vitro studies of HIV-infected
      lymphocytes have shown that hydroxyurea: (i) inhibits viral DNA synthesis; (ii)
      synergistically interacts with nucleoside reverse transcriptase inhibitors
      (NRTI); and (iii) increases the antiviral activity of didanosine. Clinical
      studies have confirmed that hydroxyurea in combination with didanosine produces
      potent and sustained viral suppression in patients with HIV infection. However,
      some concerns have been recently raised on the use of hydroxyurea in association
      with NRTI. Hydroxyurea can cause myelosuppression, skin toxicities, mild
      gastrointestinal toxicity, and abnormalities of renal and liver functions. In
      addition, hydroxyurea may accentuate the toxic effects of nucleoside analogues.
      In fact, some clinical data seem to indicate an increased risk of pancreatitis
      and neuropathy when hydroxyurea is combined with didanosine and stavudine. Since
      hydroxyurea-related toxicity is dose dependent, a systematic study of hydroxyurea
      optimal dosage and schedule was initiated to monitor patients for possible
      nucleoside toxicity. In the Research Institute for Genetic and Human Therapy
      (RIGHT) 702 study it was shown that a low, well-tolerated hydroxyurea dose (600
      mg daily) achieved better antiretroviral activity than higher doses, together
      with better CD4+ cell count increase and fewer adverse effects. In this paper the
      effects of hydroxyurea as salvage therapy for heavily pretreated patients with
      advanced HIV disease are presented. These studies have shown that some patients
      with extensive pretreatment experience and advanced disease can respond
      substantially to the addition of hydroxyurea. The addition of hydroxyurea to
      didanosine does not prevent the emergence of resistance to didanosine;
      nonetheless, the efficacy of this therapeutic regimen may not be attenuated by
      the presence of didanosine-resistant HIV mutants. Since CD4 T lymphocyte
      activation is essential for virus replication and CD8 T lymphocyte activation may
      contribute to pathogenesis, the combination of hydroxyurea with other drugs may
      lead to the inhibition of HIV, by blocking the 'cell activation-virus production
      pathogenesis' cycle. Clinical data indicate that hydroxyurea may play a role in
      attenuation of viral rebound and immune reconstitution by decreasing CD4 T cell
      proliferation, as well as preventing the exhaustion of CD8 T cell populations
      that may result from excessive activation during HIV infection. While the
      combination of hydroxyurea with didanosine has provided hope, future studies
      including those that evaluate optimal dosing and long-term toxicity are needed to
      define the role for this agent in the treatment of HIV infection.

PMID- 12814331
TI  - Benefit-risk assessment of treatments for heparin-induced thrombocytopenia.
AB  - Patients with heparin-induced thrombocytopenia (HIT) are at high risk of
      thrombosis and should be treated with alternative anticoagulant therapy to reduce
      complications. The current treatment of choice is one of the approved direct
      thrombin inhibitors, argatroban or lepirudin. These drugs have been proven to be
      safe and effective in multicentre clinical trials where dosage regimens have been
      established for prophylaxis and treatment of thrombosis. Argatroban has also been
      tested and approved for use in invasive cardiology procedures in the HIT patient.
      Dosage regimens for other clinical uses, such as cardiac surgery, have not yet
      been established for either drug. The safety and effectiveness of the thrombin
      inhibitors is dependent on their use according to established guidelines. Other
      treatment options that may be effective for the patient with HIT include dextran,
      plasmapheresis, intravenous gammaglobulin and aspirin (acetylsalicylic acid).
      Although used historically, these options have not been tested in rigorous
      clinical trials. For life- and limb-threatening thrombosis, thrombolytic agents
      and/or surgery may provide benefit. Because the risk of bleeding is high from
      these procedures, they should be performed only by an experienced practitioner.
      Several studies have shown that patients with HIT requiring continued
      anticoagulation are best managed with a warfarin derivative initiated while under
      full anticoagulation with a thrombin inhibitor. There is a risk of skin necrosis
      and bleeding if guidelines for dose administration and monitoring of warfarin are
      not followed. Subsequent use of heparin or a low molecular weight heparin after
      resolution of the clinical episode of HIT can be hazardous, particularly within
      the first 3 months. If laboratory testing is negative, heparin may be cautiously
      reinstituted for short-term use (1-2 hours) with monitoring for platelet count
      decrease and thromboembolism. The pregnant patient with HIT requiring
      anticoagulation represents a particular challenge, where there is no drug of
      choice at present. Although today there are realistic treatment options for the
      patient with HIT, the morbidity and mortality associated with this disease have
      not been eliminated. Awareness and early treatment of HIT remain important
      components of the clinical care for patients exposed to heparins. Future
      therapeutic developments based on a better understanding of the pathophysiology
      of HIT may further improve clinical outcomes. Despite some limitations, the
      current treatment options for patients with HIT provide unparalleled benefit
      compared with the treatment options available only a few years ago.

PMID- 12814333
TI  - Extended safety profile of oral clodronate after long-term use in primary breast
      cancer patients.
AB  - INTRODUCTION: Long-term safety and tolerance is paramount when treating women who
      are otherwise healthy after the primary adjuvant therapy of breast cancer.
      Efficacy and limited safety results of a large-scale clinical trial, using
      adjuvant oral clodronate to prevent bone metastases in primary breast cancer
      patients, have been reported previously, demonstrating a reduction in the rate of
      bone metastases during treatment. Here we present expanded safety and
      tolerability results for clodronate treatment from this trial (cut-off date
      extended from June 1997 to June 2000). STUDY DESIGN AND METHODS: For this
      randomised, double-blind, placebocontrolled, multicentre study, patients were
      enrolled and randomised to receive oral clodronate (Bonefos) 1600 mg/day or
      placebo for 2 years. The total median treatment period plus follow-up was 5.5
      years. Adverse events (AEs) and laboratory parameters were followed up regularly
      for the total study period. The 95% CIs were estimated for the difference in the
      rate of AEs between the treatment groups. PATIENTS: A total of 1079 women with
      primary operable breast cancer were enrolled to the study; 538 received
      clodronate and 541 received placebo. RESULTS: Overall incidence of AEs (96.5% of
      the patients) was the same in both treatment groups, although gastrointestinal
      disorders were significantly more frequent in the clodronate group during the
      total study period (66% vs 56.2%; 95% CI 4.0-15.6; p < 0.05). This was mainly due
      to an increase in non-severe diarrhoea beginning 3-4 months after treatment
      start. Serious AEs (SAEs) were reported for 39.4% of the patients receiving
      clodronate and 44.5% of those receiving placebo; no drug-related (clodronate or
      placebo) SAEs were identified. Clodronate significantly lowered mortality (98
      deaths vs 129 deaths; hazard ratio 0.77; 95% CI 0.59-1.00; p = 0.047) reducing
      the risk of death over the total study period by 23%. AEs caused 58 early
      discontinuations (five drug-related events) in the clodronate group and 43
      discontinuations (three drug-related events) in the placebo group. CONCLUSION:
      These results indicate that in women with early breast cancer receiving adjuvant
      systemic therapy, oral clodronate for 2 years is generally well tolerated with no
      serious long-term sequelae, providing a safe, long-term therapy in the adjuvant
      setting.

PMID- 12814332
TI  - Treatment of psychosis in Parkinson's disease: safety considerations.
AB  - Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much
      more commonly, psychosis is induced by drug therapy for Parkinson's disease and
      is the strongest known risk factor for nursing home placement. Delusions are less
      frequent than hallucinations, but are more concerning as they are often paranoid
      in nature. Treatment begins with a search for correctable infectious, toxic, and
      metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications
      are slowly reduced. However, withdrawal of these drugs usually worsens
      parkinsonism and is often not tolerated. Certain atypical antipsychotics can be
      used to treat psychosis without compromising motor function. The choice of
      atypical antipsychotic is largely based on ease of use and adverse effect profile
      as most have comparable efficacy in improving psychosis. Currently, there are
      five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and
      ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not
      been reported in Parkinson's disease. The most common adverse effects of
      clozapine in Parkinson's disease are sedation, orthostatic hypotension and
      sialorrhoea. Sedation is generally helpful since these patients are frequently
      awake at night and tend to have worse behavioural problems then. Clozapine does
      not induce deterioration of motor function, but it has the potential to cause
      agranulocytosis, which is idiosyncratic and not dose-related. In risperidone
      treated Parkinson's disease patients, reported adverse effects include
      somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium,
      fatigue, leg cramps, depression, urinary incontinence and hypotension. Although
      in some Parkinson's disease studies, risperidone has been well tolerated, others
      have shown that many patients are unable to tolerate the drug due to
      deterioration of motor function. While an initial study of olanzapine in
      Parkinson's disease psychosis showed the drug to be effective without
      deterioration of motor function, succeeding reports demonstrated a deleterious
      effect of the drug on motor functioning. The most common adverse effects of
      quetiapine in Parkinson's disease patients are sedation and orthostatic
      hypotension. There is a lack of double-blind trials; however, cumulative reports
      involving >200 Parkinson's disease patients strongly suggest that quetiapine is
      well tolerated and effective. Unlike clozapine, it does not improve tremor and
      may induce mild deterioration of motor function. Recently, cholinesterase
      inhibitors have been reported to alleviate psychosis in Parkinson's disease.
      Although ondansetron, an antiemetic with antiserotonergic properties, has been
      reported to relieve psychosis in Parkinson's disease, its prohibitive cost has
      prevented further study in this population. Electroconvulsive treatment is
      generally reserved for the patient with psychotic depression who is unable to
      tolerate any pharmacological therapy.

PMID- 12814334
TI  - Prevalence of joint disease in patients with psoriasis: implications for therapy.
AB  - Joint diseases are common among patients with psoriasis. Psoriatic arthritis, the
      most important of these, can be defined as a rheumatoid factor-negative
      inflammatory arthritis associated with psoriasis and has emerged as a specific
      disease independent from rheumatoid arthritis. Psoriatic arthritis is divided
      into several clinical subsets, which is helpful in differentiating it from other
      types of inflammatory arthritis. The prevalence of arthritis in patients with
      psoriasis may be far higher than the previously accepted average of 7%. In a
      recent study of 5,795 members of the Nordic Psoriasis Associations, the
      prevalence was found to be 30%. Arthritis has a significant impact on quality of
      life in patients with psoriasis. These factors should be recognised as they have
      implications for therapy, since a number of drugs can delay or stop joint damage
      when given in time. This also applies to the new biologic agents, although at
      present these therapies are generally restricted to patients non-responsive to
      other available drugs. Alone or in combination, the new drugs may achieve higher
      response rates and have better safety profiles than older therapies. However,
      long-term experience is still lacking and, unfortunately, the new drugs will be
      far from affordable by all for some time to come.

PMID- 12814335
TI  - Cutaneous lupus erythematosus: diagnosis and management.
AB  - Cutaneous lupus erythematosus (CLE) includes a variety of lupus erythematosus
      (LE)-specific skin lesions that are subdivided into three categories - chronic
      CLE (CCLE), subacute CLE (SCLE) and acute CLE (ACLE) - based on clinical
      morphology, average duration of skin lesions and routine histopathologic
      examination. This paper describes our personal experience in the management of
      CLE over the last 30 years, with details on preferential therapeutic options
      related to clinical, histologic and immunopathologic aspects of each clinical
      subset of the disease. Effective sunscreening and sun protection are considered
      the first rule in the management of CLE because of the high degree of
      photosensitivity of the disease. Antimalarial agents are crucial in the treatment
      of CLE and are the first-line systemic agents, particularly in discoid LE (DLE)
      and SCLE. Dapsone is the drug of choice for bullous systemic LE (BSLE) as well as
      for LE in small dermal vessels (e.g. leukocytoclastic vasculitis). Retinoids,
      known as second-line drugs for systemic therapy, are sometimes used to treat
      chronic forms of CLE and are particularly successful in treating hypertrophic LE.
      Systemic immunosuppressive agents are required to manage the underlying systemic
      LE disease activity in patients with ACLE. These drugs, especially azathioprine,
      methotrexate, cyclophosphamide and cyclosporine, together with corticosteroids,
      constitute third-line systemic therapy of CLE. In our experience, oral prednisone
      or parenteral 'pulsed' methylprednisolone are useful in exacerbations of disease
      activity. Thalidomide provides one of the most useful therapeutic alternatives
      for chronic refractory DLE, although its distribution is limited to a few
      countries because of the risk of teratogenicity and polyneuropathy. However,
      medical treatment with local corticosteroids remains the mainstay of CLE
      treatment, especially for DLE. Patient education regarding the disease is also
      important in the management of CLE, because it helps relieve undue anxiety and to
      recruit the patient as an active participant in the treatment regimen.

PMID- 12814336
TI  - Dermabrasion in dermatology.
AB  - Dermabrasion has been used for a number of years to treat a variety of
      dermatologic conditions, including facial skin resurfacing and scar revision. The
      popularity of this procedure has diminished with the advent of newer procedures
      including chemical exfoliation, laser resurfacing, non-ablative laser
      resurfacing, and microdermabrasion. Dermabrasion found its niche in treating acne
      and traumatic facial scars, and in cosmetic facial resurfacing. Small, portable
      hand-held dermabraders are the most popular units available today and are able to
      generate rotation speeds of 18,000-35,000 revolutions per minute. End pieces,
      including wire brushes, diamond fraises and serrated wheels, attach to the end of
      the dermabrader to allow precise resurfacing and treatment. As with all cosmetic
      surgical procedures, appropriate patient selection and room preparation (with
      appropriate lighting and monitoring equipment) are essential to assure optimal
      outcomes with the dermabrasion procedure. Patients must understand all of the
      potential risks, benefits and limitations associated with the procedure. Patients
      must also be aware of alternative therapies that are available. Dermabrasion is
      technique-dependent and the surgeon should be well versed on the technique prior
      to performing this therapy. Gentian violet solution is used to delineate the
      areas to be treated. Refrigerant topical anesthesia is used to freeze the skin
      prior to the procedure. Holding the skin taut, the dermabrasion procedure occurs
      in a routine manner, treating one anatomic unit at a time. Postoperatively,
      patients may have an open or closed dressing system. Postoperative medical
      treatment is also recommended, including the use of antiviral agents,
      antibacterials and corticosteroids. The re-epithelialization process is usually
      complete in 5-7 days and residual erythema is common for up to 4 weeks. Adequate
      sun protection is essential following dermabrasion. Dermabrasion has also been
      used in combination with other dermatologic procedures, including chemical
      exfoliation, soft tissue augmentation and laser procedures, to enhance the
      results of dermabrasion. Dermabrasion remains a useful facial skin resurfacing
      and scar revision technique, particularly when performed by a trained and skilled
      surgeon. Most dermatologic surgeons argue that pure dermabrasion is a useful
      modality in skilled surgical hands and should be considered when appropriate.

PMID- 12814337
TI  - Topical acne drugs: review of clinical properties, systemic exposure, and safety.
AB  - This review examines the commonly available topical acne agents and factors that
      determine their percutaneous absorption. Reported and theoretical adverse effects
      from systemic exposure are detailed. The topical retinoid class, which includes
      tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin
      and erythromycin, are regulated by prescription in most countries. Used
      appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of
      active ingredient into the circulation. Clear-cut links to systemic toxicity in
      humans are practically nonexistent, except in the case of topical clindamycin,
      which has been associated with diarrhea rarely, and there have been 2 cases of
      pseudomembranous colitis reported. Birth defects have occurred in two patients
      treated with tretinoin and one patient treated with adapalene, but causation was
      not proven. Another prescription drug, 20% azelaic acid, is associated with
      relatively high systemic exposure, which is presumed innocuous because it is a
      normal dietary constituent whose endogenous levels are not altered by topical
      use. Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are
      available in concentrations of 2% or more in over-the-counter acne treatments and
      some prescription products. All of these agents are known to exhibit some degree
      of percutaneous absorption. They remain largely unregulated because, other than
      skin irritation, only local allergic contact dermatitis from benzoyl peroxide in
      about 2.5% of patients and rare local and systemic hypersensitivity reactions
      from sodium sulfacetamide have been reported. Salicylism has occurred using
      methyl salicylate ointments and high concentrations of salicylic acid on
      widespread areas of hyperkeratotic skin, but there are no known cases resulting
      from salicylic acid acne products. Caution is advised in special circumstances,
      such as during childhood, pregnancy, lactation and concomitant therapy with other
      drugs, because relevant studies are lacking. Animal data support avoidance of
      many topical agents, particularly known teratogens such as retinoids and
      salicylic acid, in pregnant women. Salicylate avoidance is advised during
      lactation, because aspirin use carries the risk of bleeding disorders in nursing
      infants.

PMID- 12814338
TI  - Isotretinoin use and subsequent depression and suicide: presenting the evidence.
AB  - The growing number of reported cases of depression and suicide associated with
      isotretinoin (a retinoid receptor agonist) use in patients with acne has prompted
      concern among dermatologists, patients, and their relatives and has triggered new
      warnings from regulators including depression-related, patient-informed consent
      forms. In establishing a cause-effect relationship, it is useful to judiciously
      consider whether there is an association, what is the nature of that association,
      if there is a plausible biological mechanism of action, the validity and
      reliability of measures used and the strength of study designs. Hoffmann-La Roche
      estimates that by April 2001 approximately 12 million patients worldwide have
      used isotretinoin, with 5 million patients in the US.A MEDLINE search between
      January 1966 and May 14 2003 of the published medical literature found 24
      documented cases of isotretinoin-associated depression, with 3 suicides. One
      additional patient committed suicide during the fourth month of isotretinoin
      treatment and 3 further patients attempted suicide by taking an overdose of
      isotretinoin. The US FDA's Adverse Event Reporting System (AERS) contains almost
      23,000 reports for isotretinoin from its approval in 1982 to December 2002. As of
      November 30, 2002, AERS contained 3,104 reports (US and foreign) with at least
      one reported psychiatric event. The FDA is aware of 173 reports of suicide (both
      US and foreign) in association with isotretinoin. Reports of positive dechallenge
      and rechallenge present a strong signal pointing to an association between
      isotretinoin and depression. A Hoffmann-La Roche sponsored epidemiological study
      failed to find any evidence of an association between isotretinoin and depression
      or suicide. However, the design of the study was flawed and the evidence was
      deemed inconclusive. Further studies using strong study designs, reliable and
      valid measures, and adequate sample sizes may bring us closer to the answer. The
      evidence suggesting a relationship between isotretinoin and depression needs to
      be weighed against the increasing prevalence of depression among adolescents and
      young adults and the psychological impact of acne. The literature contains
      credible evidence that isotretinoin treatment may reduce the psychosocial impact
      of acne in some patients. At the present time, there is no known pharmacological
      mechanism that would account for psychiatric symptomatology as a result of
      isotretinoin treatment; however, retinoid receptors are widely distributed in the
      brain and more research is needed to ascertain whether they have a role in
      depression. In the meantime, for the practitioner, the obvious benefit of
      isotretinoin in treating acne should encourage continued use. However, patients
      and their relatives must be informed and depressive symptoms should be actively
      assessed at each visit and, if necessary, referral to a psychiatrist,
      antidepressant therapy or discontinuation of isotretinoin should be considered.

PMID- 12814339
TI  - The efficacy of calcipotriol + acitretin combination therapy for psoriasis:
      comparison with acitretin monotherapy.
AB  - BACKGROUND: Although the use of an oral retinoid as monotherapy is an effective
      treatment for psoriasis, it is usually used in combination with other topical or
      systemic therapies including topical corticosteroids, UVB phototherapy, psoralens
      + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid
      adverse effects. AIM: To compare the efficacy of the calcipotriol + acitretin
      combination treatment with acitretin alone over a long period in Korean patients
      with psoriasis. METHODS: A randomized, bilateral paired comparison was conducted
      involving 40 patients with psoriasis who received calcipotriol + acitretin
      combination therapy and 20 psoriasis patients who received acitretin alone. The
      initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each
      visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and
      adverse effects. The maximum dose was 40 mg/day. The treatment duration for all
      patients ranged from 4-52 weeks. After 12 weeks, the efficacy of therapy,
      according to Psoriasis Area and Severity Index scores, was assessed. At the end
      of the study (52 weeks), we selected patients who had achieved complete clearance
      and compared the duration of treatment and total dose of acitretin used in both
      groups. RESULTS: After 12 weeks, 16 patients (40%) achieved complete clearance in
      the calcipotriol + acitretin group and 3 patients (15%) in the acitretin
      monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the
      calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy
      group achieved complete clearance. The duration of treatment and total dose of
      retinoid required to achieve clearance were slightly lower in the calcipotriol +
      acitretin combination group, however, this was not statistically significant.
      With the exception of liver enzyme elevation (which affected more patients in the
      acitretin monotherapy group than in the combination group), adverse effects were
      not significantly different. DISCUSSION: Our results showed that calcipotriol
      might enhance the clinical outcome of systemic acitretin therapy. More large,
      well-controlled, long-term studies need to be conducted to determine whether
      there is indeed a beneficial effect of the addition of calcipotriol to acitretin
      treatment and whether this effect is maintained over long-term periods.

PMID- 12814340
TI  - Cutaneous drug reaction case reports: from the world literature.
AB  - Skin disorders are the most common adverse reactions attributed to drugs. Any
      skin disorder can be imitated, induced or aggravated by drugs. To help you keep
      up-to-date with the very latest skin reactions occurring with both new and
      established drugs, this section of the journal brings you information selected
      from the adverse drug reaction alerting service Reactions Weekly. The following
      case reports are selected from the very latest to be published in the world
      dermatology literature. Any claim of a first report has been verified by a search
      of AdisBase (a proprietary database of Adis International) and Medline. In
      addition, the World Health Organization (WHO) Adverse Drug Reactions database is
      also searched. This database, maintained by the Uppsala Monitoring Centre in
      Sweden, is the largest and most comprehensive adverse drug reaction source in the
      world, with information obtained from National Centers of 65 affiliate countries.
      Each case report is assessed for seriousness using the FDA MedWatch definition of
      serious (patient outcome is: death; life-threatening; hospitalization;
      disability; congenital anomaly; or requires intervention to prevent permanent
      impairment or damage).

PMID- 12814342
TI  - New frontiers in gene targeting and cloning: success, application and challenges
      in domestic animals and human embryonic stem cells.
AB  - Until recently, precise modification of the animal genome by gene targeting was
      restricted to the mouse because germline competent embryonic stem cells are not
      available in any other mammalian species. Nuclear transfer (NT) technology now
      provides an alternative route for cell-based transgenesis in domestic species,
      offering new opportunities in genetic modification. Livestock that produce human
      therapeutic proteins in their milk, have organs suitable for xenotransplantation,
      or that could provide resistance to diseases such as spongiform encephalopathies
      have been produced by NT from engineered, cultured somatic cells. However,
      improvements in the efficiency of somatic cell gene targeting and a greater
      understanding of the reprogramming events that occur during NT are required for
      the routine application of what is currently an inefficient process. The ability
      to reprogramme and genetically manipulate cells will also be crucial for full
      exploitation of human embryonic stem (hES) cells, which offer unparalleled
      opportunities in human health and biotechnology. Particularly pertinent are
      directed differentiation of hES lines to specific cell lineages, production of
      cells that evade the patient's immune system and ensuring the safety of ensuing
      transplants. This review will discuss some of the successes, applications and
      challenges facing gene targeting in livestock and hES cells.

PMID- 12814341
TI  - Effect of a null mutation of the oviduct-specific glycoprotein gene on mouse
      fertilization.
AB  - The mammalian fertilization process takes place in a complex microenvironment
      within the female genital tract. A member of the chitinase protein family,
      oviduct-specific glycoprotein (OGP), has been identified in oviductal fluid from
      various mammalian species, including humans. Although OGP is widely believed to
      be involved in the process of mammalian fertilization, including spermatozoon
      function and gamete interactions, based on experimental results obtained in
      vitro, its physiological significance remains controversial. The present study
      established OGP gene-null ( ogp (-/-)) mice, and primarily characterized their
      reproductive properties to study the physiological function(s) of OGP. Results
      obtained from studies using an in vivo or in vitro system showed that the
      fertility of ogp (-/-) females was within normal limits. These results indicate
      that OGP is not essential for the process of in vivo fertilization, at least in
      mice.

PMID- 12814343
TI  - The genetic basis of infertility.
AB  - Infertility is defined as the inability to conceive after one year of regular
      unprotected intercourse; approximately one in six couples wishing to start a
      family fall into this category. Although, in many cases, the diagnosis is simply
      'unexplained', a variety of reasons including lack of ovulation, mechanical
      stoppage, sperm deficiencies and parental age have been implicated. It is
      difficult to assess accurately the overall magnitude of the contribution of
      genetics to infertility as most, if not all, conditions are likely to have a
      genetic component, for example susceptibility to infection. Nevertheless, a
      significant number of infertility phenotypes have been associated with specific
      genetic anomalies. The genetic causes of infertility are varied and include
      chromosomal abnormalities, single gene disorders and phenotypes with
      multifactorial inheritance. Some genetic factors influence males specifically,
      whereas others affect both males and females. For example, chromosome
      translocations affect both males and females, whereas Klinefelter syndrome and
      the subsequent infertility phenotype caused by it are specific to males. This
      article reviews current research in the genetic basis of infertility; gender
      specific disorders and those affecting both sexes are considered.

PMID- 12814344
TI  - Influence of oocyte-secreted factors and culture duration on the metabolic
      activity of bovine cumulus cell complexes.
AB  - Intracellular communication between the cumulus cell complex and the oocyte is
      essential for numerous processes during oocyte maturation. The aim of this study
      was to determine the interaction between oocyte-secreted factors and the
      metabolic activity of bovine cumulus cell complexes during in vitro maturation
      (IVM). Cumulus-oocyte complexes (COCs) were aspirated from ovaries derived from
      an abattoir and divided into four treatment groups: (i) intact COCs, (ii)
      oocytectomized complexes (OOX), in which the ooplasm was microsurgically removed,
      (iii) OOX co-cultured with denuded oocytes (OOX+DO) and (iv) DO. The complexes
      were cultured individually in IVM media. After 0-4, 10-14 and 20-24 h of culture,
      the utilization of oxygen, glucose, pyruvate and L-lactate by the complexes was
      measured. The metabolic activity of the DO was undetectable. There were no
      significant differences in metabolic measurement among any of the treatment
      groups, indicating that the metabolism of the cumulus complex is not affected by
      the presence of the oocyte. When metabolic activity for the complexes was
      analysed relative to time in culture, there was an approximate twofold increase
      in the consumption of oxygen, glucose and pyruvate over the 24 h period (P<0.05),
      although production of L-lactate remained constant. The relationship between
      total glucose uptake and L-lactate production indicated that the majority of
      glucose consumed at the start of culture was being utilized via glycolysis, but
      by the cessation of the maturation period, there was significant utilization of
      glucose elsewhere, possibly for the formation of cumulus extracellular matrix.
      These results indicate that metabolism of COC does not reflect biochemical
      activity of the oocyte. Nevertheless, the metabolic requirements of the COC
      increase throughout maturation.

PMID- 12814345
TI  - Demonstration of a non-steroidal, non-inhibin factor in the ovine corpus luteum
      of pregnancy that reduces pituitary responsiveness to GnRH-induced LH secretion
      in vitro.
AB  - The decline in pulsatile LH secretion and pituitary responsiveness to GnRH as
      pregnancy advances may be due to non-steroidal factors secreted by the ovine
      corpus luteum of pregnancy. Corpora lutea from ten ewes on days 70-80 of
      gestation were homogenized, charcoal-treated and, together with charcoal-treated
      follicular fluid from superovulated women, were subjected to inhibin
      immunoaffinity chromatography, reducing dimeric inhibin A and B by >90% and
      abolishing inhibin bioactivity. These preparations were investigated using
      cultures of rat pituitary cells. GnRH-induced LH and FSH secretion in vitro was
      reduced by ovine corpus luteum extract and human follicular fluid by 47+/-5% and
      42+/-5% of control LH and by 37+/-5% and 50+/-10% of control FSH, respectively
      (P<0.001). Extracts prepared from corpora lutea and placentae that were collected
      on days 50, 90 and 120 of pregnancy (five ewes per stage of pregnancy) showed
      increased GnRH-induced LH-suppressing bioactivity, particularly in the case of
      the placental extracts, with a threefold increase in activity. When partially
      purified by pseudochromatofocusing, GnRH-induced LH-suppressing bioactivity in
      extracts of ovine corpora lutea was identified at pH 5.40 and 5.77. Although
      these values are similar to published gonadotrophin surge-attenuating factor
      (GnSAF) bioactivity pI values, a GnSAF-blocking antiserum had no consistent
      effect on ovine corpus luteum extract GnRH-induced LH-suppressing bioactivity. It
      was concluded that the ovine corpus luteum of pregnancy contains a non-steroidal,
      non-inhibin factor, probably not GnSAF, that has the ability to reduce pituitary
      responsiveness to GnRH in vitro.

PMID- 12814346
TI  - Immunolocalization and protein expression of the alpha subunit of the large
      conductance calcium-activated potassium channel in human myometrium.
AB  - Large-conductance calcium-activated potassium (BKCa) channels play an important
      role in the control of myometrial excitability. The aim of the present study was
      to determine the localization and protein expression of the alpha subunit of BKCa
      channels in the pregnant and parturient human uterus. An anti-alpha BKCa channel
      monoclonal antibody (anti-alpha(995-1113)) was used to localize and quantitate
      immunoreactive BKCa channel protein in myometrium of singleton term pregnant
      women undergoing either elective (n=26) or emergency Caesarean section following
      the onset of spontaneous labour (n=25). Data are presented as medians
      (interquartile range). Differences between groups were analysed using the Mann
      Whitney U test. Immunohistochemistry studies localized the alpha subunit of the
      BKCa channel to the plasma membrane and the cytosol of myometrial cells with
      similar reaction end product in pregnant women who were or were not undergoing
      labour. Expression of this subunit, observed as a 125 kDa band in western blots,
      was significantly higher in pregnant women who were not undergoing labour (30.6%
      (20.3, 43.9)) than in those who were undergoing labour (15.7% (11.3, 22.4);
      P<0.01). Reduced BKCa alpha subunit expression in pregnant women during labour
      may underlie the initiation of uterine contractility during parturition.

PMID- 12814347
TI  - Contraceptive responses of mice immunized with purified recombinant mouse zona
      pellucida subunit 3 (mZP3) proteins.
AB  - Mouse zona pellucida subunit 3 (mZP3) was tested for efficacy as an
      immunocontraceptive antigen by comparing the fertility of mice immunized with
      recombinant mZP3 proteins. Recombinant protein was expressed using either the
      vaccinia virus T7 mammalian (vmZP3 protein) or baculovirus insect cell (bmZP3
      protein)-expression systems. Female BALB/c or wild mice were immunized by i.p.
      injection using Freund's complete adjuvant and boosted three times with affinity
      purified recombinant proteins in Freund's incomplete adjuvant. Most mice
      developed antibodies that crossreacted to the respective mZP3 antigens by ELISA
      or western blot. In BALB/c mice immunized with vmZP3, fertility and mean litter
      size were reduced transiently to 25% and 10%, respectively, of those of control
      mice. However, immunization with bmZP3 did not affect either the fertility or
      mean litter sizes in BALB/c or wild mice immunized with bmZP3. The results
      demonstrate that reduction in fertility can be achieved in female BALB/c mice
      immunized using Freund's adjuvants and recombinant mZP3 protein produced in a
      mammalian, but not an insect, cell-expression system. Arguments are presented for
      the likely role of glycosylation of the mZP3 antigen in inducing contraceptive
      immune responses.

PMID- 12814348
TI  - Effect of different nutritional regimens before ovulation on plasma
      concentrations of metabolic and reproductive hormones and oocyte maturation in
      gilts.
AB  - This study examined the effect of feeding either a maintenance (1.35 kg day(-1))
      or high (3.5 kg day(-1)) plane of nutrition for 19 days after oestrus on oocyte
      maturity and both reproductive and metabolic hormone concentrations in gilts.
      Blood samples were collected each day from oestrus until slaughter on day 19 and
      during two pulse bleeds (15 min samples for 8 h) conducted on day 12 and day 18.
      After slaughter, oocytes were recovered from the presumed ovulatory population of
      follicles, matured in vitro for 46+/-2 h with 10% of their own follicular fluid,
      and then fixed and stained to determine the stage of nuclear maturation of the
      oocyte. Gilts fed the high diet had a higher proportion of oocytes that reached
      metaphase II than gilts fed the maintenance diet (88.3+/-2.71% versus 68.2+/
      6.48%; P=0.013). Circulating concentrations of insulin-like growth hormone I (IGF
      I) and the number of LH pulses were lower (P<0.05) in gilts fed the maintenance
      diet compared with gilts fed the high diet on day 12 and day 18. Mean oestradiol
      and progesterone concentrations were higher (P<0.05) for gilts fed the
      maintenance diet compared with gilts fed the high diet. Leptin concentrations
      were also higher on day 19 in gilts fed the high diet (2.16+/-0.26 ng ml(-1)
      (n=9) versus 3.20+/-0.32 (n=11), P=0.025). The results of this study indicate
      that improved oocyte quality (increased proportion of oocytes that reached
      metaphase II) is associated with a number of changes in reproductive and
      metabolic hormones. Further studies are required to indicate which hormonal
      mechanism may, in turn, lead to increased embryo survival and eventual litter
      size.

PMID- 12814349
TI  - Expression of the exocytotic protein syntaxin in mouse oocytes.
AB  - Syntaxin is an integral membrane protein that is involved in membrane fusion. The
      exocytosis of the contents of cortical granules, secretory vesicles located in
      the cortex of an egg, modify the extracellular environment to block additional
      spermatozoa from penetrating the newly fertilized egg. The aim of this study was
      to characterize syntaxin expression in mouse oocytes, and to determine the
      specific isoform that is expressed. Syntaxin was demonstrated in the mouse ovary
      and in mouse oocytes by both western blot and reverse transcription-polymerase
      chain reaction analyses. Syntaxin 4 was specifically expressed in metaphase II
      oocytes. Syntaxin was also immunolocalized within metaphase II oocytes and one
      cell embryos with pronuclei using laser scanning confocal microscopy. In
      metaphase II oocytes, syntaxin was located on the plasma membrane and in the
      cortex, where cortical granules are present, but was not seen at sites free of
      cortical granules. In one-cell embryos, no cytoplasmic region was free of
      syntaxin immunoreactivity. Immunoelectron microscopy detected syntaxin on both
      the plasma membrane and the vesicle membranes in mouse metaphase II oocytes. In
      conclusion the results indicate that syntaxin 4 co-localizes with cortical
      granules and participates in membrane fusion and exocytosis during the cortical
      reaction.

PMID- 12814350
TI  - Inhibition of the basal and oestradiol-stimulated mitotic activity of primary
      spermatogonia by melatonin in the testis of the frog, Rana esculenta, in vivo and
      in vitro.
AB  - Melatonin has a direct inhibitory effect on the basal and oestradiol-stimulated
      mitotic activity of primary spermatogonia in the testis of the frog, Rana
      esculenta. In this study oestradiol was used to induce spermatogonial
      proliferation to verify the anti-proliferative effect of melatonin. The
      colchicine metaphase arrest technique was used. The results obtained from in vivo
      experiments confirm that oestradiol increases the mitotic index of primary
      spermatogonia and, for the first time, indicate that melatonin has an inhibitory
      role on the proliferation of primary spermatogonia in the frog testis. Similar
      results were obtained from testes of melatonin-injected frogs that were exposed
      to oestradiol in vitro; in fact spermatogonia were unresponsive to hormonal
      stimulation. In addition, in short-term cultured testes, melatonin (at
      physiological concentration) interferes with the effects of oestradiol on
      spermatogonial proliferation, supporting the hypothesis that melatonin exerts the
      inhibitory effect directly via its local action on the frog gonads. Morphological
      observation after in vivo or in vitro melatonin treatments indicates that Leydig
      cells display degenerative features, whereas in adjacent germinal tubules,
      Sertoli cells show heterochromatic nuclei. These results indicate that melatonin
      may act on Leydig cells and confirm that there is a paracrine interaction between
      interstitial and germinal compartments. The results of the present study
      indicate, for the first time, that melatonin may be directly involved in the
      inhibitory control of spermatogonial proliferation in the testis of the frog, R.
      esculenta.

PMID- 12814351
TI  - Mitogenic and anti-apoptotic activity of insulin on bovine embryos produced in
      vitro.
AB  - Insulin improves development of mammalian preimplantation embryos and, in
      addition to the regulation of glucose transport, it exerts mitogenic and anti
      apoptotic activities. The expression of glucose transporters (Glut) mediating the
      uptake of this essential energy substrate is critical for embryo survival. An
      impaired expression of Glut leads to an increase in apoptosis at the blastocyst
      stage and involves Bax. The various effects of insulin were unravelled by
      supplementing the in vitro culture medium with insulin (1.7 micromol l(-1)) and
      (i) the rates of cleavage and blastocyst development were recorded; (ii)
      mitogenic activity was studied by determining the total number of blastocyst
      cells and the ratio between trophectoderm and inner cell mass (ICM) cells; (iii)
      the frequency of apoptosis in blastocysts was determined by the TdT-mediated duTP
      nick-end labelling (TUNEL) assay and by quantification of the relative amounts of
      mRNA for Bax and Bcl-XL; and (iv) expression for Glut1, Glut3 and Glut8
      transcripts was compared between embryos cultured in the presence or absence of
      insulin. Insulin increased rates of cleavage (81.2+/-2.2 (control) to 86.0+/-2.5)
      and blastocyst development (24.7+/-1.9 to 31.3+/-1.2), and number of blastocyst
      cells (123.7+/-6.0 to 146.3+/-6.6); the increase in the number of blastocyst
      cells was due to a significantly higher number of trophectoderm cells (82.3+/-5.0
      versus 100.3+/-5.5). Blastocysts derived from cultures supplemented with insulin
      showed a significant decrease in apoptosis as determined by the TUNEL assay
      (14.8+/-0.9 to 12.2+/-0.7). No effects of insulin on the mRNA expression of Glut
      isoforms and Bax and Bcl-XL were found. These results demonstrate that the
      mitogenic and anti-apoptotic effects of insulin on bovine preimplantation embryos
      did not correlate with changes in the amounts of mRNA for the glucose transporter
      isoforms Glut1, -3 and -8, or transcripts for Bax and Bcl-XL.

PMID- 12814352
TI  - The FecB (Booroola) gene acts at the ovary: in vivo evidence.
AB  - The aim of this study was to differentiate between pituitary and ovarian actions
      of the FecB gene by measuring the ovarian response to a standardized treatment
      with gonadotrophins designed to mimic the changes in FSH and LH that occur in the
      follicular phase of the ovarian cycle in ewes, with (Fec(B/-), n=6) and without
      (Fec(+/+), n=9) the gene, that were rendered hypogonadotrophic by pretreatment
      with a potent antagonist of GnRH. Ewes with ovarian autotransplants were used to
      facilitate the assessment of follicular function by the collection of ovarian
      venous blood and ultrasonography. The gonadotrophin regimen resulted in
      concentrations of FSH and LH that were similar to concentrations found in a
      normal cycle and did not differ between genotypes. Follicular development and
      ovulation occurred in all animals, and patterns of secretion of oestradiol,
      androstenedione and inhibin A were normal. Despite these endocrine similarities,
      the antral follicle population stimulated by FSH infusion retained the
      characteristic genotypic difference with the ovaries of Fec(+/+) animals
      containing a range of follicle sizes with decreasing proportions of small (<3.5
      mm in diameter) and medium (3.5-4.5 mm in diameter) follicles as well as large
      follicles (> or =4.5 mm in diameter), whereas the ovaries of Fec(B/-) ewes
      contained no follicles of >4.5 mm in diameter. This genotypic difference was
      retained after ovulation with gene carriers having more preovulatory
      follicles/corpora lutea (3.8+/-0.3) of a smaller diameter (5.3+/-0.3 mm) than did
      non-gene carriers (1.7+/-0.3; 11.4+/-0.9 mm; P<0.05). As ewes carrying the FecB
      gene mutation were able to ovulate more follicles than non-gene carriers, despite
      identical concentrations and patterns of FSH and LH stimulation, the results of
      this study support the hypothesis that the FecB gene acts at the ovary to enhance
      ovarian sensitivity to gonadotrophic stimulation.

PMID- 12814353
TI  - Expression and activity of Apaf1 and caspase-9 in granulosa cells during
      follicular atresia in pig ovaries.
AB  - Apoptosis in granulosa cells plays a crucial role in ovarian follicular atresia,
      but the intracellular regulating mechanism, especially the mitochondrion
      dependent apoptosis signalling pathway, is still largely unknown. This study
      examined whether the mitochondrial pathway is associated with granulosa cell
      apoptosis during atresia in pig ovaries. Both mRNAs of caspase-9 and apoptotic
      protease-activating factor 1 (Apaf1), which are major signal transducing
      components in the mitochondrial pathway, were detected in granulosa cells in
      healthy, early atretic and progressed atretic follicles by RT-PCR. No changes in
      the expression of Apaf1 mRNA were seen during follicular atresia, but the
      expression of caspase-9 mRNA increased during atresia. Apaf1 protein was steadily
      detected in granulosa cells prepared from healthy, early atretic and progressed
      atretic follicles by western blot analysis, but high expression of the precursor
      of caspase-9 (procaspase-9) was detected only in granulosa cells of healthy
      follicles. Decreased procaspase-9 protein was demonstrated during follicular
      atresia. Proteolytic activity of caspase-9 increased during atresia, in agreement
      with the diminution of procaspase-9 protein. Intensive expression of caspase-9
      mRNA was demonstrated in the granulosa cells of early atretic and progressed
      atretic follicles but not in those of healthy follicles. These results indicate
      that the mitochondrial signalling pathway, which is mediated by Apaf1 and caspase
      9, plays a crucial role in determining the fate of granulosa cells during atresia
      in pig ovaries.

PMID- 12814354
TI  - Phospholipase C and protein kinase C involvement in mouse embryonic stem-cell
      proliferation and apoptosis.
AB  - Activation of the phosphatidylinositol (PtdIns) signal transduction system
      involves stimulation of phospholipase C (PLC) by hormones and other agonists to
      produce two second messengers, the inositol phosphate, Ins(1,4,5)P3 which
      releases calcium from intracellular stores, and diacylglycerol which activates
      protein kinase C (PKC). This study, using activators or inhibitors of PLC and PKC
      and a calcium ionophore, examined the role of the PtdIns system in mouse
      embryonic stem (ES) cells. The PLC inhibitor, U-73122, inhibited ES-cell
      proliferation and also inhibited PLC activation as evidenced by a decrease in
      inositol phosphate formation in response to fetal calf serum stimulation. The two
      PKC activators, the diacylglycerol analogue 1,2, dioctanoyl-sn-glycerol (DOG) and
      the phorbol ester 12-O-tetra-decanoyl phorbol 13-acetate (TPA), increased cell
      proliferation in a dose-dependent manner, as did the calcium ionophore,
      ionomycin. However, co-stimulation with either ionomycin and DOG or ionomycin and
      TPA resulted in a reduced number of cells. The PKC inhibitor, bisindolylmaleimide
      II (Bis II), significantly decreased the number of ES cells, mainly due to
      increased apoptosis. The possible feedback effect of PKC on PLC was examined by
      preincubating ES cells with either the PKC inhibitor Bis II or the activator TPA
      before stimulation of inositol phosphate production with fetal calf serum;
      preincubation with Bis II increased inositol phosphate formation whereas
      preincubation with TPA decreased inositol formation. These results indicate that
      the PtdIns system is involved in the control of ES-cell proliferation and
      apoptosis.

PMID- 12814355
TI  - Differential routing of coexisting neuropeptides in vasopressin neurons.
AB  - The functional implications of intraneuronal coexistence of different
      neuropeptides depend on their respective targeting to release sites. In the rat
      hypothalamic magnocellular neurons, we investigated a possible differential
      routing of the coexpressed galanin and vasopressin. The respective location of
      proteins and messengers was assessed with double immunogold and in situ
      hybridization combining confocal and electron microscope analysis. The various
      populations of labelled granules were quantitatively compared in three
      subcellular compartments: perikarya, local processes and posthypophyseal nerve
      endings. Three subpopulations of granules were detected in all three
      compartments, but their respective amount showed significant differences. Galanin
      alone was immunolocalized in some secretory granules, vasopressin alone in
      others, and both peptides in a third subpopulation of granules. The major part of
      the granules containing vasopressin, either alone or in association with galanin,
      is found in neurohypophyseal nerve endings. In contrast, galanin single-labelled
      granules represent the most abundant population in dendritic processes, while
      double-labelled granules are more numerous in perikarya. This indicates a
      preferential distribution of the two peptides in the different compartments of
      magnocellular neurons. Furthermore, galanin and vasopressin messenger RNAs were
      detected at different domains of the endoplasmic reticulum, suggesting that
      translation might also occur at different locations, thus leading to partial
      segregation of galanin and vasopressin cargoes between two populations of
      secretory granules. The present study provides, for the first time in mammals,
      evidence suggesting that galanin and vasopressin are only partly copackaged and
      undergo a preferential targeting toward dendrites or neurohypophysis, suggesting
      different functions, autocrine/paracrine and endocrine, respectively.

PMID- 12814356
TI  - A hVIPR transgene as a novel tool for the analysis of circadian function in the
      mouse suprachiasmatic nucleus.
AB  - A mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen
      et al. (2000) PNAS, 97, 11575-11580) was used to investigate circadian function
      in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R,
      detected by a beta-galactosidase (beta-GAL) tag, have a distinct distribution
      within the SCN, closely matching that of neurophysin (NP) neurons and extending
      into the region of peptide histidine isoleucine (PHI) cells. In common with NP
      and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by
      synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN
      cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression
      antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in
      the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2
      in hVPAC2R cells confirmed their photic responsiveness. Having established their
      circadian properties, we tested the utility of SCN neurons expressing the hVIPR
      transgene as functionally and anatomically explicit markers for SCN tissue
      grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation
      into adult CD1 mice, and expressed beta-GAL, PER and PHI. Over a series of
      studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of
      72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR
      transgenic grafts on a heterozygous Clock mutant background we confirmed that
      restored activity rhythms were conferred by the donor tissue. We conclude that
      the hVIPR transgene is a powerful and flexible tool for examination of circadian
      function in the mouse SCN.

PMID- 12814357
TI  - Intracellular calcium release resulting from mGluR1 receptor activation modulates
      GABAA currents in wide-field retinal amacrine cells: a study with caffeine.
AB  - The modulatory action of calcium (Ca2+) released from intracellular stores on
      GABAA receptor-mediated current was investigated in wide-field amacrine cells
      isolated from the teleost, Morone chrysops, retina. Caffeine, ryanodine or
      inositol 1,4,5-triphosphate (IP3) markedly inhibited the GABAA current by
      elevating [Ca2+]i. The inhibition resulted from the activation of a Ca2+-->
      Ca2+/calmodulin --> calcineurin cascade. Long (>12 s) exposure to glutamate
      mimicked the caffeine effect, i.e. it inhibited the GABAA current by elevating
      [Ca2+]i through mGluR1 receptor activation and consequent IP3 generation. This
      pathway provides a 'timed' disinhibitory mechanism to potentiate excitatory
      postsynaptic potentials in wide-field amacrine cells. It occurs as a result of
      the suppression of GABA-mediated conductances as a function of the duration of
      presynaptic excitatory input activity. This is much like some forms of long-term
      potentiation in the central nervous system. In a local retinal circuit this will
      selectively accentuate particular excitatory inputs to the wide-field amacrine
      cell. Similar to other neural systems, we suggest that activity-dependent
      postsynaptic disinhibition is an important feature of the signal processing in
      the inner retina.

PMID- 12814358
TI  - Role of heme oxygenase-1 protein in the neuroprotective effects of cyclopentenone
      prostaglandin derivatives under oxidative stress.
AB  - Previously we found that some cyclopenteone prostaglandin derivatives (PGs),
      referred to as neurite outgrowth-promoting PGs (NEPPs), have dual biological
      activities of promoting neurite outgrowth and preventing neuronal death [Satoh et
      al. (2000) J. Neurochem., 75, 1092-1102; Satoh et al. (2001) J. Neurochem., 77,
      50-62; Satoh et al. (2002) In Kikuchi, II. (ed.), Strategenic Medical Science
      Against Brain Attack. Springer-Verlag, Tokyo, pp. 78-93]. To investigate possible
      cellular mechanisms of the neuroprotective effects, we performed oligo
      hybridization-based DNA array analysis with mRNA isolated from HT22, a cell line
      that originated from a mouse hippocampal neuron. Several transcripts up-regulated
      by NEPP11 were identified. Because heme oxygenase 1 (HO-1) mRNA was the most
      prominently induced and was earlier reported to protect neuronal and non-neuronal
      cells against oxidative stress, we focused on it as a possible candidate
      responsible for the neuroprotective effects. We found NEPP11 to induce HO-1
      protein (32 kDa) in HT22 cells in both the presence and the absence of glutamate,
      whereas non-neuroprotective prostaglandins (PGs) Delta12-PGJ2 or PGA2 did not.
      Overexpression of HO-1-green fluorescence protein (GFP) fusion protein
      significantly protected HT22 cells against oxidative glutamate toxicity, whereas
      that of GFP alone did not. Furthermore, biliverdin and bilirubin, products of HO
      1 enzymatic activity on heme, protected HT22 cells from oxidative glutamate
      toxicity. These results, together with our previous results, suggest that NEPP11
      activates the expression of HO-1 and that HO-1 produces biliverdin and bilirubin,
      which result in the inhibition of neuronal death induced by oxidative stress.
      NEPP11 is the first molecular probe reported to have a neuroprotective action
      through induction of HO-1 in neuronal cells.

PMID- 12814359
TI  - Cloning and characterization of an ionotropic glutamate receptor subunit
      expressed in the squid nervous system.
AB  - In this paper we describe the cloning of a putative ionotropic glutamate receptor
      subunit, SqGluR, and its distribution in the nervous system of the squid. A full
      length cDNA was assembled from a cDNA library of the stellate ganglion/giant
      fibre lobe complex of Loligo opalescens. The deduced amino acid sequence of the
      mature SqGluR displayed 44-46% amino acid identity with mammalian GluR1-GluR4 and
      53% with Lym-eGluR1 from Lymnaea stagnalis. In situ hybridizations in adult squid
      confirmed that the SqGluR mRNA is abundant in giant fibre lobe neurons, in large,
      presumptive motor neurons of the stellate ganglion proper and in the
      supraoesophageal and optic lobes of the central nervous system. In newborn squid,
      SqGluR mRNA expression was detected throughout the nervous system but not
      elsewhere. A synthetic peptide corresponding to the last 15 amino acids of the
      SqGluR C-terminus was used to generate polyclonal antibodies, which were used for
      immunoblot analysis to demonstrate widespread expression in the squid central and
      peripheral nervous systems. Injection of the synthetic peptide into the
      postsynaptic side of the giant synapse inhibited synaptic transmission.

PMID- 12814360
TI  - Purinergic receptors on microglial cells: functional expression in acute brain
      slices and modulation of microglial activation in vitro.
AB  - Microglial cells are the pathologic sensors in the brain. ATP released from
      damaged cells is a candidate for signalling neural injury to microglia. Moreover,
      ATP is an extracellular messenger for propagating astrocyte activity in the form
      of Ca2+ waves. To test for the functional expression of purinoreceptors in
      microglial cells we employed the patch-clamp technique in acute slices of adult
      mouse brain. ATP triggered a nonselective cationic and a K+ current.
      Pharmacological screening with purinergic ligands indicated the presence of P2Y1
      and P2Y2/4 receptors linked to the activation of a K+ current and P2X receptors,
      including P2X7, linked to the activation of a nonselective cationic current.
      These findings suggest that microglial cells in situ express different purinergic
      receptors with distinct sensitivity and functional coupling. To test for the
      involvement of purinoreceptors in microglial activation, we stimulated cultured
      microglial cells with lipopolysaccharide and measured the release of tumour
      necrosis factor alpha, interleukin-6, interleukin-12 and macrophage inflammatory
      protein 1alpha, induction of K+ outward currents and nitric oxide release. All
      these parameters were reduced in the presence of purinergic ligands, indicating
      that purinergic receptor activation attenuated indicators of microglial
      activation.

PMID- 12814361
TI  - Expression patterns and subcellular localization of the Down syndrome candidate
      protein MNB/DYRK1A suggest a role in late neuronal differentiation.
AB  - The Minibrain (Mnb) gene belongs to a new protein kinase family, which is
      evolutionarily conserved, and probably plays several roles during brain
      development and in adulthood. In Drosophila, mnb is involved in postembryonic
      neurogenesis and in learning/memory. In humans, MNB has been mapped within the
      Down syndrome critical region of chromosome 21 and is overexpressed in the Down
      syndrome embryonic brain. It has been widely proposed that MNB is involved in the
      neurobiological alterations associated with Down syndrome. Nevertheless, little
      is known about the functional role that MNB plays in vertebrate brain
      development. We have recently shown [Hammerle et al. (2002) Dev. Biol., 246, 259
      273] that in early vertebrate embryos, Mnb is transiently expressed in neural
      progenitor cells during the transition from proliferating to neurogenic
      divisions. Here we have studied in detail a second wave of Mnb expression, which
      takes place in the brain of intermediate and late vertebrate embryos. In these
      stages, MNB seems to be restricted to certain populations of neurons, as no
      consistent expression was detected in astroglial or oligodendroglial cells.
      Interestingly, MNB expression takes place at the time of dendritic tree
      differentiation and is initiated by a transient translocation from the cytoplasm
      to the nucleus. Afterwards, MNB protein is transported to the growing dendritic
      tree, where it colocalizes with Dynamin 1, a putative substrate of MNB kinases.
      We propose that MNB kinase is involved in the signalling mechanisms that regulate
      dendrite differentiation. This functional role helps to build a new hypothesis
      for the implication of MNB/DYRK1A in the developmental aetiology of Down syndrome
      neuropathologies.

PMID- 12814363
TI  - Perturbation of CD44 function affects chiasmatic routing of retinal axons in
      brain slice preparations of the mouse retinofugal pathway.
AB  - Neurons generated early in development of the ventral diencephalon have been
      shown to play a key role in defining the midline and the caudal boundary of the
      optic chiasm in the mouse retinofugal pathway. These functions have been
      attributed to a surface bound adhesion molecule, CD44 that is expressed in these
      chiasmatic neurons. In this study, we investigated the effects of perturbing
      normal CD44 functions on axon routing in brain slice preparations of the mouse
      retinofugal pathway. Two CD44 antibodies (Hermes-1 and IM7) were used that bind
      to distinct epitopes on the extracellular domain of the molecule. We found that
      both antibodies produced dramatic defects in routing of the retinal axons that
      arrive early in the chiasm. In preparations of embryonic day 13 (E13) and E14
      pathways, the crossed component in the chiasm was significantly reduced after
      antibody treatment. However, such reduction in axon crossing was not observed in
      E15 chiasm, indicating that the lately generated crossed axons lost their
      responses to CD44. Furthermore, the anti-CD44 treatment produced a reduction in
      the uncrossed component in the E15 but not in younger pathways, suggesting a
      selective response of the lately generated axons, mostly from ventral temporal
      retina, but not those generated earlier, to the CD44 at the chiasmatic midline in
      order to make their turn for the uncrossed pathway. These findings provide
      evidence that a normal function of CD44 molecules in the chiasmatic neurons is
      essential for axon crossing and axon divergence at the mouse optic chiasm.

PMID- 12814362
TI  - Expression of oncostatin M receptor beta in a specific subset of nociceptive
      sensory neurons.
AB  - Oncostatin M belongs to the interleukin-6 family of cytokines and acts as a
      multifunctional cytokine during murine embryogenesis and in inflammatory
      reactions. Although it has been demonstrated that oncostatin M has biological
      activities on many types of cells, including hepatocytes, dermal fibroblasts and
      endothelial cells, the roles of oncostatin M in the murine peripheral nervous
      system remain unclear. Here, we investigated the expression of specific beta
      subunit of oncostatin M receptor in the dorsal root ganglia of adult mice. In the
      adult dorsal root ganglia, beta-subunit of oncostatin M receptor was exclusively
      expressed in small-sized neurons. Approximately 13% of total dorsal root ganglia
      neurons in mice contained beta-subunit of oncostatin M receptor. The double
      immunofluorescence method revealed that approximately 28% of beta-subunit of
      oncostatin M receptor-positive neurons contained TrkA immunoreactivity, 63%
      expressed Ret immunoreactivity and 58% bound isolectin B4. No neuropeptides,
      including substance P and calcitonin gene-related peptide, were contained in the
      neurons. In addition, all beta-subunit of oncostatin M receptor-positive neurons
      expressed both vanilloid receptor 1 and P2X3 purinergic receptor. These neurons
      projected to the inner portion of lamina II in the dorsal horn of spinal cord and
      the dermis of skin. Seven days after sciatic nerve axotomy, the expression of
      beta-subunit of oncostatin M receptor was down-regulated in the lumbar dorsal
      root ganglia of the injured side. Our study demonstrated that beta-subunit of
      oncostatin M receptor was expressed in both cell bodies and processes of
      nonpeptidergic nociceptive neurons in adult mice, suggesting that oncostatin M
      may affect the nociceptive function of the neurons through the modulation of
      vanilloid receptor 1 and P2X3 expression.

PMID- 12814364
TI  - Molecular biology and electrophysiology of neuronal nicotinic receptors of rat
      chromaffin cells.
AB  - Neuronal nicotinic acetylcholine receptors of chromaffin cells in the adrenal
      medulla are physiologically activated by acetylcholine to mediate catecholamine
      release into the bloodstream. The present study examined the subunit composition
      and functional properties of rat chromaffin cell neuronal nicotinic acetylcholine
      receptors using molecular biology, immunocytochemistry and whole-cell patch
      clamp. Reverse transcription-polymerase chain reaction analysis indicated the
      presence of alpha2, alpha3, alpha4, alpha5, alpha7, beta2 and beta4 transcripts
      (alpha6 and beta3 could not be detected). Immunocytochemistry revealed most cells
      positive for alpha3, beta2, beta4 and alpha5 proteins. Few cells were
      immunoreactive for alpha2 and alpha4, while none was for alpha7. At single-cell
      level, colocalization could be demonstrated for alpha3alpha5 and alpha4beta2.
      Western blot analysis confirmed antibody specificity for alpha3, alpha4, alpha5,
      beta2 and beta4 subunits. Inward currents elicited by nicotine pulses were
      insensitive to alpha-bungarotoxin and low doses of methyllycaconitine,
      demonstrating lack of functional alpha7 receptors. Partial block of nicotine
      currents was observed with either AuIB alpha-conotoxin (selective against
      alpha3beta4 receptors) or MII alpha-conotoxin (selective against alpha3beta2
      receptors). With high concentrations of co-applied toxins, antagonism occlusion
      developed, suggesting loss of subunit selectivity. Antagonism by dihydro-beta
      erythroidine summated nonlinearly with AuIB and MII inhibition, confirming
      heterogeneity of neuronal nicotinic acetylcholine receptor block. The present
      results suggest that the most frequently encountered receptors of rat chromaffin
      cells should comprise alpha3beta4, alpha3beta2 with the addition of alpha5
      subunits. Because of the prevailing subunit composition, rat chromaffin cell
      neuronal nicotinic acetylcholine receptors are suitable models, particularly for
      the alpha3beta4 subclasses of mammalian brain receptors recently demonstrated in
      discrete cerebral areas.

PMID- 12814365
TI  - Differential modulation of NMDA-induced calcium transients by arachidonic acid
      and nitric oxide in cultured hippocampal neurons.
AB  - We have examined the effect of arachidonic acid on the transient increases in
      intracellular Ca2+ evoked by NMDA and AMPA in cultured hippocampal pyramidal
      cells loaded with Fura-2 AM. Repeated brief pulses of NMDA elicited Ca2+
      transients that showed a modest run down. This run down was enhanced if the
      preparation was shielded from UV light and was reduced by conducting the
      experiments in the presence of the nitric oxide synthase inhibitor l
      nitroarginine (100 micro m). Arachidonic acid (2 micro m) enhanced the Ca2+
      transients evoked by NMDA but not those evoked by AMPA. Other C20 unsaturated
      fatty acids did not alter the time course of the response to NMDA. These
      experiments suggest that elevated intracellular Ca2+ activates nitric oxide
      synthase and the resulting synthesis of nitric oxide depresses the Ca2+ response
      to NMDA while arachidonic acid augments these responses. Therefore two substances
      implicated in synaptic plasticity (arachidonic acid and nitric oxide)
      differentially modulate NMDA-mediated Ca2+ entry into hippocampal neurons.

PMID- 12814366
TI  - Axonal morphogenesis controlled by antagonistic roles of two CRMP subtypes in
      microtubule organization.
AB  - During development, cells undergo dynamic morphological changes by rearrangements
      of the cytoskeleton including microtubules. However, molecular mechanisms
      underlying the microtubule remodeling between orientated and disoriented
      formations are almost unknown. Here we found that novel subtypes of collapsin
      response mediator proteins (CRMP-As) and the originals (CRMP-Bs), which occur
      from the alternative usage of different first coding exons, are involved in this
      conversion of microtubule patterns. Overexpression of CRMP2A and CRMP2B in chick
      embryonic fibroblasts induced orientated and disoriented patterns of
      microtubules, respectively. Moreover, sequential overexpression of another
      subtype overcame the effect of the former expression of the countersubtype.
      Overexpression experiments in cultured chick retinae showed that CRMP2B promoted
      axon branching and suppressed axon elongation of ganglion cells, while CRMP2A
      blocked these effects when co-overexpressed. Our findings suggest that the
      opposing activities of CRMP2A and CRMP2B contribute to the cellular morphogenesis
      including neuronal axonogenesis through remodeling of microtubule organization.

PMID- 12814367
TI  - Laminar differences in plasticity in area 17 following retinal lesions in kittens
      or adult cats.
AB  - Circumscribed retinal lesions in adult cats result in a reorganization of
      circuitry in area 17 such that neurons in the lesion projection zone (LPZ) can
      now be activated, not from their original receptive fields (RFs) but from regions
      of normal retina adjacent to the lesion ('ectopic' RFs). We have studied this
      phenomenon further by making circumscribed monocular retinal lesions in 8-week
      old kittens and recording responses to visual stimuli of neurons in the LPZ of
      area 17 when these cats reached adulthood. These responses have been compared
      with those in adult-lesioned cats either of relatively short postlesion survival
      (2-24 weeks) or long postlesion survival (3.5-4.5 years). In both kitten-lesioned
      and adult-lesioned animals most LPZ neurons recorded from the supragranular
      layers (II and III) not only exhibited new ectopic RFs when stimuli were
      presented via the lesioned eye but the RF properties (e.g. the sizes of
      excitatory RFs, orientation and direction selectivities, velocity preferences and
      upper cut-off velocities) were often indistinguishable from those seen when
      stimuli were presented via the nonlesioned eye. Similarly, in both kitten
      lesioned and adult-lesioned animals, most LPZ neurons recorded from the granular
      and infragranular layers (IV, V, VI), like those recorded from the supragranular
      layers, were binocular. However, in adult-lesioned but not in kitten-lesioned
      animals, the responses and the upper cut-off velocities of LPZ cells recorded
      from the granular and infragranular layers to stimuli presented via ectopic RFs
      tended to be, respectively, substantially weaker and lower than those for stimuli
      presented via the nonlesioned eye. The age-related laminar differences in
      reorganizational plasticity of cat striate cortex correlate with the lamino
      temporal pattern of distribution of N-methyl-d-aspartate glutamate receptors in
      striate cortex.

PMID- 12814368
TI  - GAP-43 mRNA and protein expression in the hippocampal and parahippocampal region
      during the course of epileptogenesis in rats.
AB  - In order to reveal axonal rewiring in the hippocampal and parahippocampal regions
      after status epilepticus, we investigated the temporal evolution of growth
      associated protein-43 (GAP-43) mRNA and protein expression in two rat models of
      mesial temporal lobe epilepsy (MTLE). Status epilepticus (SE) was induced by
      electrical stimulation of the angular bundle or by intraperitoneal kainic acid
      (KA) injections. Despite increased GAP-43 mRNA expression in dentate granule
      cells at 24 h after SE, GAP-43 protein expression in the inner molecular layer
      (IML) of the dentate gyrus decreased progressively after 24 h after SE in both
      models. Nevertheless robust mossy fiber sprouting (MFS) was evident in the IML of
      chronic epileptic rats. Remaining GAP-43 protein expression in the IML in chronic
      epileptic rats did not correlate with the extent of MFS, but with the number of
      surviving hilar neurons. In the parahippocampal region, GAP-43 mRNA expression
      was decreased in layer III of the medial entorhinal area (MEAIII) in parallel
      with extensive neuronal loss in this layer. There was a tendency of GAP-43 mRNA
      up-regulation in the presubiculum, a region that projects to MEAIII. With regard
      to this parahippocampal region, however, changes in GAP-43 mRNA expression were
      not followed by protein changes. The presence of the presynaptic protein GAP-43
      in a neurodegenerated MEAIII indicates that fibers still project to this layer.
      Whether reorganization of fibers has occurred in this region after SE needs to be
      investigated with tools other than GAP-43.

PMID- 12814369
TI  - Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice
      lacking the nociceptin precursor polypeptide or the nociceptin receptor.
AB  - Nociceptin/orphanin FQ (N/OFQ) is the endogenous agonist of the N/OFQ peptide
      receptor (NOP receptor). It is released from a larger precursor polypeptide,
      called prepro-nociceptin (ppN/OFQ) from which, in addition to N/OFQ, other
      biologically active neuropeptides may be derived. Increasing evidence indicates
      that exogenous application of N/OFQ to the central nervous system of mice and
      rats induces pro- and antinociceptive effects depending on the dose and site of
      administration. Much less is known about a potential contribution of endogenous
      N/OFQ to pain control. Here, we have used a genetic approach to address this
      topic. Mice deficient in either the NOP receptor (NOP-R-/- mice) or the N/OFQ
      precursor polypeptide (ppN/OFQ-/- mice) or both (double knockout mice) were
      compared with wild-type littermates in animal models of acute and tonic pain.
      Nociceptive responses to acute noxious heat of all three types of mutant mice
      were indistinguishable from those of wild-type mice. Accordingly, nociceptive
      behaviour was very similar in the early phase of the formalin test. However, NOP
      R-/-, ppN/OFQ-/- and double knockout mice showed markedly stronger nociceptive
      responses during prolonged nociceptive stimulation in the second phase of the
      formalin test and significantly lower thermal pain thresholds in inflamed tissue
      after zymosan A injection. These results indicate that N/OFQ contributes
      significantly to endogenous pain control during prolonged nociceptive stimulation
      but does not affect acute pain sensitivity. Among the three types of mutant mice
      nociceptive behaviour was nearly identical, indicating that the lack of other
      potential ppN/OFQ products in the ppN/OFQ-/- mice was apparently without effect
      on the nociceptive phenotype.

PMID- 12814370
TI  - Tremor-related activity of neurons in the 'motor' thalamus: changes in firing
      rate and pattern in the MPTP vervet model of parkinsonism.
AB  - The pathophysiology of parkinsonian tremor remains a matter of debate with two
      opposing hypotheses proposing a peripheral and a central origin, respectively. A
      central origin of tremor could arise either from a rhythmic activity of the
      internal segment of the globus pallidus (GPi) or from a structure such as the
      thalamus, outside the basal ganglia. In this study, single-unit recordings were
      performed in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys
      within the GPi and within three territories of the motor thalamus (delimited by
      their afferent inputs from the GPi, the substantia nigra and the cerebellum,
      respectively). For each recorded neuron, we compared the variations in firing
      rate and pattern in tremor and no tremor periods. Tremor either occurred
      spontaneously or was induced by external stimulation. When the animals entered
      into a tremor period we observed: (i) an increase in the mean firing rate in
      about half of the recorded neurons of the motor thalamus; and (ii), a change from
      an irregular to a rhythmic discharge within the range of tremor frequency (5-7
      Hz) in about 10% of the recorded neurons of the motor thalamus (pallidal and
      cerebellar territories) and the GPi. Most of the thalamic neurons that exhibited
      a rhythmic discharge during tremor were found to be sensitive to external
      stimulation. Because the changes in firing rate occurred predominantly in the
      motor thalamus and not in the GPi, and because a fast rhythmic discharge of 10-15
      Hz was frequently observed in the GPi and not in the motor thalamus, we conclude
      that thalamic activity is not a simple reproduction of basal ganglia output.
      Moreover, we suggest that thalamic processing of basal ganglia outputs could
      participate in the genesis of tremor, and that this thalamic processing could be
      influenced by sensory inputs and/or changes in attentional level elicited by
      external stimulation.

PMID- 12814371
TI  - Early life adversity programs changes in central 5-HT neuronal function in
      adulthood.
AB  - Early life adversity is associated with an increased incidence of psychiatric
      illness in adulthood. Although the mechanisms underlying this association are
      unclear, one possible substrate is brain 5-hydroxytryptamine neurotransmission,
      which is reportedly abnormal in several psychiatric disorders. This study
      examined the effect of a rat model of early life adversity, early maternal
      separation, on 5-hydroxytryptamine neurotransmission in adulthood. In vitro
      electrophysiological experiments revealed that, in early maternal separation rats
      compared with controls, the sensitivity of alpha1-adrenoceptors on 5
      hydroxytryptamine neurons in the dorsal raphe nucleus was significantly reduced,
      whilst the sensitivity of 5-hydroxytryptamine1A receptors showed a nonsignificant
      trend to reduction. In in vivo microdialysis experiments, the 5
      hydroxytryptamine1A receptor agonist-induced suppression of 5-hydroxytryptamine
      release in the frontal cortex was reduced in early maternal separation animals,
      suggesting desensitization of 5-hydroxytryptamine1A autoreceptors. There was no
      increase in basal 5-hydroxytryptamine in the frontal cortex as measured by
      microdialysis and a nonsignificant trend towards increased basal firing activity
      of classical (non-bursting) 5-hydroxytryptamine neurons in the dorsal raphe
      nucleus measured by in vivo electrophysiology. Finally, early maternal separation
      failed to alter expression of messenger ribonucleic acids coding for 5
      hydroxytryptamine1A or alpha1B receptors in the dorsal raphe nucleus as measured
      by in situ hybridization histochemistry, suggesting that functional changes in
      receptor sensitivity observed are not due to changes in receptor gene
      transcription. The findings demonstrate that early life adversity programs
      changes in sensitivity of the two principal regulators of 5-hydroxytryptamine
      neuronal activity. Similar effects in humans may contribute to the increased
      incidence of psychiatric illness in individuals exposed to early life adversity.

PMID- 12814372
TI  - Antidepressant and anxiolytic-like effects in mice lacking the group III
      metabotropic glutamate receptor mGluR7.
AB  - Glutamatergic neurotransmission has been strongly implicated in the
      pathophysiology of affective disorders, such as major depression and anxiety. Of
      all glutamate receptors, the role of group III metabotropic glutamate receptors
      (mGluR4, mGluR6, mGluR7, mGluR8) in such disorders is the least investigated
      because of the lack of specific pharmacological tools. To this end, we examined
      the behavioural profiles of mice with a targeted deletion of the gene for mGluR7
      (mGluR7-/-) in animal models of depression and anxiety. mGluR7-/- mice were
      compared with wild-type (mGluR7+/+) littermates and showed substantially less
      behavioural immobility in both the forced swim test and the tail suspension test.
      Both behavioural paradigms are widely used to predict antidepressant-like
      activity. Further, mGluR7-/- mice displayed anxiolytic activity in four different
      behavioural tests, i.e. the light-dark box, the elevated plus maze, the staircase
      test, and the stress-induced hyperthermia test, while their cognitive performance
      was normal in the passive avoidance paradigm. Analysis of locomotor activity in a
      novel environment demonstrated that mGluR7-/- mice were slightly more active in
      the initial minutes following placement in the chamber only. Together, these data
      suggest that mGluR7 may play a pivotal role in mechanisms that regulate
      behavioural responses to aversive states. Therefore, drugs acting at mGluR7 may
      provide novel treatments for psychiatric disorders such as depression and
      anxiety.

PMID- 12814373
TI  - Decreased ethanol preference and wheel running in Nurr1-deficient mice.
AB  - Nurr1 (Nr4a2) is a transcription factor expressed in dopamine cells from early
      development and throughout life. Null mutants for Nurr1 lack the ventral midbrain
      dopamine neurons and die soon after birth. Animals with a heterozygous deletion
      are viable and display no apparent abnormality. We have investigated the impact
      of heterozygous deletion of Nurr1 on ethanol consumption in adult mice as a model
      for drug-induced reward and on wheel running as a model for natural reward.
      Interestingly, Nurr1 heterozygous mice never developed high ethanol consumption
      nor did they develop as much running behaviour as did the wild-type animals.
      Thus, Nurr1 appears to have a key role for the reinforcing properties of ethanol
      and running that underlies the development of excessive reward-seeking behaviours
      characteristic for addiction. Quantitative trait loci mapping using C57Bl/6 and
      DBA/2 mice describe a locus for ethanol preference on chromosome 2, wherein Nurr1
      is located. We found two dinucleotide repeats in the Nurr1 promoter that were
      longer in mice with low preference for ethanol (DBA/2 and 129/Sv) than in mice
      with high preference for ethanol (C57Bl/6J and C57Bl/6NIH). These sequential data
      are compatible with Nurr1 as a candidate gene responsible for the quantitative
      trait loci for ethanol preference on mouse chromosome 2. Together, our data thus
      imply involvement of Nurr1 in the transition to a state of high ethanol
      consumption as well as in the development of a high amount of wheel running in
      mice.

PMID- 12814374
TI  - Morphine withdrawal precipitated by specific mu, delta or kappa opioid receptor
      antagonists: a c-Fos protein study in the rat central nervous system.
AB  - We have recently shown concurrent changes in behavioural responses and c-Fos
      protein expression in the central nervous system in both naive and morphine
      dependent rats after systemic administration of the opioid antagonist naloxone.
      However, because naloxone acts on the three major types of opioid receptors, the
      present study aimed at determining, in the same animals, both changes in
      behaviour and c-Fos-like immunoreactivity after intravenous injection of
      selective opioid antagonists, such as mu (beta-funaltrexamine, 10 mg/kg), delta
      (naltrindole, 4 mg/kg) or kappa (nor-binaltorphimine, 5 mg/kg) opioid receptor
      antagonists, in naive or morphine-dependent rats. In a first experimental series,
      only beta-funaltrexamine increased c-Fos expression in the eight central nervous
      system structures examined, whereas no effect was seen after naltrindole or nor
      binaltorphimine administration in naive rats. These results suggest a tonic
      activity in the endogenous opioid peptides acting on mu opioid receptors in
      normal rats. A second experimental series in morphine-dependent rats showed that
      beta-funaltrexamine had the highest potency in the induction of classical signs
      of morphine withdrawal syndrome, as well as the increase in c-Fos expression in
      the 22 central nervous system structures studied, suggesting a major role of mu
      opioid receptors in opioid dependence. However, our results also demonstrated
      that naltrindole and, to a lesser extent, nor-binaltorphimine were able to induce
      moderate signs of morphine withdrawal and relatively weak c-Fos protein
      expression in restricted central nervous system structures. Therefore, delta and
      kappa opioid receptors may also contribute slightly to opioid dependence.

PMID- 12814375
TI  - Deficits in spatial learning and synaptic plasticity induced by the rapid and
      competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by
      increasing endogenous brain-derived neurotrophic factor.
AB  - Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes
      prostaglandins from arachidonic acid; it plays a crucial role in inflammation in
      both central and peripheral tissues. Here, we describe its role in synaptic
      plasticity and spatial learning in vivo via an effect on brain-derived
      neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa).
      We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long
      term potentiation (LTP; the major contemporary model of synaptic plasticity), and
      causes substantial and sustained deficits in spatial learning in the watermaze.
      Increases in BDNF and PGE2 following spatial learning and LTP were also blocked.
      Importantly, 4 days of prior exercise in a running wheel increased endogenous
      BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and
      restored a parallel increase in LTP and learning-related BDNF and PGE2. In
      control experiments, we found that BSCI had no effect on baseline synaptic
      transmission or on the nonhippocampal visible-platform task; there was no
      evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids;
      there was no difference in blood corticosterone levels as measured by
      radioimmunoassay in any condition. Thus, COX plays a previously undescribed,
      permissive role in synaptic plasticity and spatial learning via a BDNF-associated
      mechanism.

PMID- 12814376
TI  - Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus
      following water maze training.
AB  - The impact was examined of exposing rats to two life experiences of a very
      different nature (stress and learning) on synaptic structures in hippocampal area
      CA3. Rats were subjected to either (i) chronic restraint stress for 21 days,
      and/or (ii) spatial training in a Morris water maze. At the behavioural level,
      restraint stress induced an impairment of acquisition of the spatial response.
      Moreover, restraint stress and water maze training had contrasting impacts on CA3
      synaptic morphometry. Chronic stress induced a loss of simple asymmetric synapses
      [those with an unperforated postsynaptic density (PSD)], whilst water maze
      learning reversed this effect, promoting a rapid recovery of stress-induced
      synaptic loss within 2-3 days following stress. In addition, in unstressed
      animals a correlation was found between learning efficiency and the density of
      synapses with an unperforated PSD: the better the performance in the water maze,
      the lower the synaptic density. Water maze training increased the number of
      perforated synapses (those with a segmented PSD) in CA3, both in stressed and,
      more notably, in unstressed rats. The distinct effects of stress and learning on
      CA3 synapses reported here provide a neuroanatomical basis for the reported
      divergent effects of these experiences on hippocampal synaptic activity, i.e.
      stress as a suppressor and learning as a promoter of synaptic plasticity.

PMID- 12814377
TI  - Piriform cortex functional heterogeneity revealed by cellular responses to
      odours.
AB  - The role of the piriform cortex (PC) in olfactory information processing remains
      mainly unknown. Indeed, until recently, only a few studies have investigated the
      response of PC neurons to odours and these studies did not take into account the
      functional heterogeneity of the PC previously described using an electrical
      stimulation paradigm. In this experiment, extracellular activity in response to
      odour was recorded in urethane anaesthetized rats in the different parts of the
      cortex ranging from anterior to posterior. A large percentage of cortical cells
      were silent at rest, and this percentage increased from anterior to posterior.
      Analysis of odour evoked activity revealed a large percentage of nonresponsive
      cells that increased from anterior to posterior. Cell activity was largely
      synchronized with breathing and different temporal patterns were observed. The
      anterior PC was characterized by odour-evoked responses phase-locked with the
      inhalation-exhalation transition period. By contrast, activity in the posterior
      PC was mainly phase-locked with inhalation or exhalation. These data confirm the
      spatial functional heterogeneity previously reported in the PC. Functional
      anatomy of the PC suggests that activity in the anterior PC can be mainly driven
      by afferent activity coming from the OB whereas posterior cells were certainly
      entrained by more complex mechanisms.

PMID- 12814378
TI  - Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of
      the left prefrontal cortex: a sham-controlled proton magnetic resonance
      spectroscopy (1H MRS) study of healthy brain.
AB  - Rapid transcranial magnetic stimulation is being increasingly used in the
      treatment of psychiatric disorders, especially major depression. However, its
      mechanisms of action are still unclear. The aim of this study was to assess
      metabolic changes by proton magnetic resonance spectroscopy following high
      frequency rapid transcranial magnetic stimulation (20 Hz), both immediately after
      a single session and 24 h after a series of five consecutive sessions. Twelve
      healthy volunteers were enrolled in a prospective single-blind, randomized study
      [sham (n = 5) vs. real (n = 7)]. Three brain regions were investigated (right,
      left dorsolateral prefrontal cortex, left anterior cingulate cortex). A single as
      well as a series of consecutive rapid transcranial magnetic stimulations affected
      cortical glutamate/glutamine levels. These effects were present not only close to
      the stimulation site (left dorsolateral prefrontal cortex), but also in remote
      (right dorsolateral prefrontal cortex, left cingulate cortex) brain regions.
      Remarkably, the observed changes in glutamate/glutamine levels were dependent on
      the pre-transcranial magnetic stimulation glutamate/glutamine concentration, i.e.
      the lower the pre-stimulation glutamate/glutamine level, the higher the
      glutamate/glutamine increase observed after short- or long-term stimulation (5
      days). In general, the treatment was well tolerated and no serious side-effects
      were reported. Neither transient mood changes nor significant differences in the
      outcome of a series of neuropsychological test batteries after real or sham
      transcranial magnetic stimulation occurred in our experiment. In summary, these
      data indicate that rapid transcranial magnetic stimulation may act via
      stimulation of glutamatergic prefrontal neurons.

PMID- 12814379
TI  - Illusory contours and specific regions of human extrastriate cortex: evidence
      from rTMS.
AB  - Functional magnetic resonance imaging studies showed that perception of illusory
      contours is associated with extrastriate cortex activation prevailing on the
      right side. 1 Hz repetitive transcranial magnetic stimulation (rTMS) is able to
      induce lasting inhibition of cortical activity. The objective of the study was to
      investigate the role of extrastriate cortex in illusory contour perception
      inducing 1 Hz rTMS interference in healthy subjects. Eight healthy subjects
      underwent 1 Hz rTMS (600 pulses) through a figure-of-eight coil over right and
      left occipital cortex (O1 and O2 of 10/20 EEG system); sham magnetic stimulation
      on the same sites and right motor cortex rTMS (in three subjects) were given as
      control. Subjects performed a computerized task requiring perception of illusory
      and real contours of Kanizsa squares in baseline and after rTMS. After stimulus
      presentation the subject made a forced-choice decision about the regularity or
      irregularity of stimulus contour, by hitting as fast as possible one of two keys
      on the computer keyboard. Reaction times (RT) were measured. Right occipital
      stimulation significantly increased RT for illusory contour perception (vs.
      baseline, P < 0.05). No significant RT changes were observed in the other
      experimental conditions with respect to the baseline condition. It is concluded
      that 1Hz rTMS of right extrastriate cortex can disrupt perception of illusory
      contours and the effect appears to be side-specific, being evident only after
      right occipital stimulation. This study supports the critical role of right
      extrastriate cortex in illusory contour perception.

PMID- 12814380
TI  - What you believe versus what you think they believe: a neuroimaging study of
      conceptual perspective-taking.
AB  - Social communication requires shared representations as well as a cognitive
      flexibility for successful interactions between self and other. What neural
      mechanisms underlie the ability to distinguish between our own perspective vs.
      the perspective of others at a conceptual level? In this PET study subjects who
      were medical students were asked according to the experimental conditions to
      respond to a list of health-related questions, taking either their own
      perspective or the perspective of a 'lay person'. Third-person perspective as
      compared to first-person perspective was associated with activation in the medial
      part of the superior frontal gyrus, in the left superior temporal sulcus, in the
      left temporal pole and in the right inferior parietal lobe. The reverse
      comparison revealed a specific activation in the postcentral gyrus for the first
      person conceptual perspective. This study provides congruent results at the
      conceptual level with previous studies investigating the neural correlates of
      self/other distinction at the motor level, and opens a new area of research in
      which conceptual cognition can be viewed in the continuity of motor cognition.

PMID- 12814381
TI  - Arm movement and gap as factors influencing the reaction time of the second
      saccade in a double-step task.
AB  - To guide our hand for reaching, we explore our visual environment by sequences of
      saccades. In the present paper, we studied the eye and hand movements of human
      subjects looking or looking and pointing at a target that is instantaneously
      displaced two times (double-step task). It was previously shown that the second
      saccade has a much longer reaction time than the first one [Feinstein & Williams
      (1972) Vision Res., 12, 33-44]. The second reaction time is even longer if the
      subject also has to point to the target with the hand [Lunenburger et al. (2000)
      Eur. J. Neurosci., 12, 4107-4116]. The conditions and objective for these effects
      are further examined in the present paper. It is shown that vision of the hand
      reduces the first and second saccadic reaction times in parallel. The second
      reaction time is prolonged for shorter delays between both target steps as well
      as for larger amplitudes of the second saccade. However, the long second reaction
      time does not reflect an absolute saccadic refractory period, because a gap
      before the second target step reduces the second reaction time to a value similar
      to the first. Hand response time and average hand velocity were increased when
      the second target step was larger. The response time for the eyes was about 30%
      of the response time of the hand. We argue that the observed effects reflect the
      coordination of eye and hand movement to allow a precise and efficient reaching
      behaviour.

PMID- 12814382
TI  - Sound presentation rate is represented logarithmically in human cortex.
AB  - The encoding of temporal information is critical to auditory processing. Since
      the mismatch negativity component of the auditory event-related brain potential
      is thought to reflect properties of auditory sensory memory, we used it to
      examine the representation of acoustic time intervals in the human cortex. The
      mismatch negativity occurs in response to deviations in acoustic regularities,
      which are stored in sensory memory. We used 16 stimulus conditions, randomly
      presenting short trains of tones with fixed onset-to-onset intervals of 100, 200,
      300 or 400 ms (all tones in the study were identical). The first four intervals
      between the tones established the acoustic regularity on each train (i.e. the
      'standard'). The fifth tone in each train was preceded by an interval that varied
      randomly among the same four intervals. If this interval was different from the
      standard for that trial, it violated the acoustic regularity (i.e. it was a
      'deviant'). The mismatch response to the fifth tone differed significantly among
      stimulus conditions and was proportional to the absolute value of the logarithm
      of the deviant/standard interval ratio. This indicates that short acoustic time
      intervals are represented with a ratio scale in the human cortex. When the fifth
      tone occurred 100 ms after the fourth, it elicited a somewhat different, although
      proportional response, supporting the hypothesis that a special integration
      mechanism may exist for very short time intervals.

PMID- 12814383
TI  - Electrophysiological properties of the utricular primary transducer are modified
      during development under hypergravity.
AB  - The electrophysiological development of hair cells between birth and the eight
      postnatal day (P8) was studied in the utricular macula of rats gestated in nest
      boxes mounted upon a centrifuge, subjecting the animals to a gravitational force
      of 2G. Whole-cell voltage-clamp recordings were made on cells in the acutely
      isolated epithelium. Cells were accessed through a tear in the epithelium, no
      enzymatic dissociation procedures were employed. Under artificially enhanced
      gravity, the whole cell conductance was dramatically altered in the two types of
      hair cells. Significant increases occurred from P3-4 in the type I cells while in
      the type II cells, the effect was delayed until P7-8. Fourfold and threefold
      increases of the mean slope conductance were observed at P7-8 in the type I and
      type II hair cells, respectively. These results indicate that the
      electrophysiological properties of a primary transducer such as utricle may be
      modified by variation of the primary stimulus during development.

PMID- 12814386
TI  - Involvement of post-synaptic kainate receptors during synaptic transmission
      between unitary connections in rat neocortex.
AB  - The properties of functional kainate receptor-mediated EPSCs were studied in
      acute slices from 19-35-day-old rats. EPSCs elicited in pyramidal and fast
      spiking cells in layers 2/3 and 5 of the rat motor cortex by extracellular single
      shock stimulus in the presence of GYKI 53655 and D-2-amino-5-phosphopentanoic
      resulted in a residual current. This current was not enhanced by cyclothiazide
      but was blocked by 6-cyano-7-nitroquinoxalin-2,3-dione and is thought to be
      mediated by kainate receptors. These kainate receptor-mediated currents displayed
      a wide range of time courses depending on which pre-synaptic fibres were
      activated. With paired recordings, unitary EPSCs elicited in pyramidal cells were
      almost totally blocked by GYKI 53655 and D-2-amino-5-phosphopentanoic. However,
      when L-transpyrrolidine-2,4-dicarboxylate (PDC), a glutamate uptake blocker, was
      introduced in the bath, the amplitude of kainate receptor-mediated currents,
      which is resistant to GYKI 53655 and D-2-amino-5-phosphopentanoic, was revealed.
      The rise and decay time constants of the kainate receptor-mediated currents were
      identical to control EPSCs. PDC was not required to reveal the kainate receptor
      mediated currents elicited in fast-spiking cells which also displayed similar
      rise and decay time constants to the control EPSCs. Excitatory input onto
      pyramidal and fast-spiking cells in the neocortex mediated by kainate receptors
      contributed between 14 and 40% of the total control unitary EPSCs which displayed
      identical time courses to the AMPA receptor-mediated component of the EPSCs. Post
      synaptic kainate receptors at connected pyramidal cell synapses may be located
      extra-synaptically.

PMID- 12814387
TI  - Measurement of the soluble angiopoietin receptor tie-2 in patients with coronary
      artery disease: development and application of an immunoassay.
AB  - BACKGROUND: The angiopoietin family has emerged as a group of crucial growth
      factors to normal angiogenesis. They are essential to the development of the
      mature vessel wall and interact with the endothelium via endothelial cell
      specific tyrosine kinase receptors, tie-1 and tie-2. The role of the tie-2
      receptor has been extensively examined in neovascularization associated with
      malignancy, but little is known about the role it may play in atherosclerosis, a
      condition whose pathophysiology also involves angiogenesis. Soluble tie-2 has
      been detected in the plasma of healthy controls, but this has yet to be applied
      to patients in the clinical setting. MATERIALS AND METHODS: We developed an ELISA
      to detect plasma tie-2 levels and applied these to a clinical setting. The intra-
      and interassay coefficients of variation for the assay were 4.7% and 9.6%,
      respectively. We then measured levels of tie-2, vascular endothelial growth
      factor (VEGF), another factor associated with angiogenesis, and the soluble VEGF
      receptor Flt-1 (sFlt-1) in 75 patients with coronary artery disease [25 with
      acute myocardial infarction (AMI), 25 with acute coronary syndromes (ACS) and 25
      with stable angina] and 25 healthy controls. RESULTS: Median [IQR, interquartile
      range] levels of tie-2 were significantly higher in the coronary artery disease
      patients (AMI 12 [10-17] ng mL-1, ACS 10 [9-14] ng mL-1, stable angina 9 [3-11]
      ng mL-1) when compared with the controls (7.5 [7-9] ng mL-1P = 0.004). As
      expected, levels of VEGF and sFlt were significantly different from those in the
      healthy controls (P = 0.011 and P < 0.001, respectively). Significant
      correlations were found between levels of tie-2 and VEGF (Spearman r = 0.59, P <
      0.001), tie-2 and sFlt-1 (r = 0.45, P < 0.001) and VEGF and sFlt-1 (r = 0.56, P <
      0.001) in the whole study group. CONCLUSION: We suggest that tie-2 may be
      potentially used as a marker of angiogenesis in atherosclerosis and may help
      elucidate the role of the angiopoietin/tie-2 system in atherogenesis.

PMID- 12814388
TI  - Individuals at increased coronary heart disease risk are characterized by an
      impaired microvascular function in skin.
AB  - BACKGROUND: To investigate whether microvascular function in skin is a valid
      model to study the relationships between cardiovascular risk factors and
      microvascular function, we investigated skin microvascular function in
      individuals with increased coronary heart disease (CHD) risk. MATERIALS AND
      METHODS: Forty-six healthy White individuals aged 30-70 years were studied.
      Coronary heart disease risk was assessed with the use of the CHD risk score
      according to the Framingham Heart Study, which is based on the risk factors age,
      blood pressure, cigarette smoking, total cholesterol, HDL cholesterol and
      diabetes. Endothelium-dependent and -independent vasodilation in skin were
      evaluated with laser Doppler after iontophoresis of acetylcholine and sodium
      nitroprusside. Videomicroscopy was used to measure recruitment of skin
      capillaries after arterial occlusion. RESULTS: Coronary heart disease risk score
      (i.e. the 10-year probability of CHD) varied from 1-37%. Microvascular function
      decreased with increasing quartiles of CHD risk (for acetylcholine-mediated
      vasodilation: 687, 585, 420 and 326%, P = 0.002; for nitroprusside-mediated
      vasodilation: 776, 582, 513 and 366%, P = 0.02; for capillary recruitment: 49.9,
      44.6, 27.2 and 26.7%, P = 0.001). These trends were similar in men and women (P
      for interaction > 0.2) and independent of body mass index. CONCLUSIONS: Increased
      CHD risk is associated with an impaired endothelium-dependent vasodilatation and
      capillary recruitment in skin, suggesting that microvascular function in skin is
      a valid model to study the relationships between cardiovascular risk factors and
      microvascular function.

PMID- 12814389
TI  - Hyperhomocysteinaemia is not associated with increased levels of asymmetric
      dimethylarginine in patients with ischaemic heart disease.
AB  - BACKGROUND: Elevated plasma total homocysteine appears to be related to
      endothelial dysfunction and impaired nitric oxide production. We aimed to
      investigate [1] whether elevated levels of plasma total homocysteine are
      associated with high plasma levels of asymmetric dimethylarginine, an endogenous
      inhibitor of nitric oxide synthase, and [2] whether reduction of plasma total
      homocysteine levels by folate and vitamin B supplementation lowers plasma
      concentration of asymmetric dimethylarginine. MATERIALS AND METHODS: Sixty
      patients with ischaemic heart disease and with plasma total homocysteine levels
      of 15.0 micromol L-1 were randomized to open therapy with folic acid, pyridoxine
      and cyancobalamin for 3 months (n = 30) or to no treatment (n = 30). Samples were
      also obtained from 34 patients with plasma total homocysteine levels of 8.0
      micromol L-1 on admission. RESULTS: Plasma asymmetric dimethylarginine
      concentrations in patients with elevated total homocysteine levels were not
      significantly higher (0.68 +/- 0.19 micromol L-1) than in patients with low total
      homocysteine levels (0.61 +/- 0.10 micromol L-1; P = 0.08). Plasma asymmetric
      dimethylarginine level in the vitamin supplemented group was 0.65 +/- 0.12
      micromol L-1 before, and 0.64 +/- 0.12 micromol L-1 after 3 months of vitamin
      supplementation (NS). Plasma asymmetric dimethylarginine levels were correlated
      with serum cystatin C levels (P < 0.001). CONCLUSION: A nonsignificant trend to
      increased plasma levels of asymmetric dimethylarginine in patients with high
      plasma total homocysteine levels may be explained by concomitant subtle renal
      dysfunction. Substantial reduction of plasma total homocysteine did not affect
      the level of plasma asymmetric dimethylarginine.

PMID- 12814390
TI  - Immune activation and degradation of tryptophan in coronary heart disease.
AB  - BACKGROUND: Inflammation and immune activation appear to be important in the
      pathogenesis of coronary heart disease (CHD). Cytokine interferon-gamma, which is
      released during cell-mediated immune responses, induces indoleamine (2,3)
      dioxygenase (IDO), an enzyme degrading tryptophan to kynurenine. Therefore,
      immune stimulation is commonly associated with an increased kynurenine to
      tryptophan ratio (kyn trp-1) indicative for activated indoleamine (2,3)
      dioxygenase and a measurable decline of tryptophan. METHODS: Blood concentrations
      of kynurenine and free tryptophan and the kynurenine to tryptophan ratio were
      examined in 35 patients with coronary heart disease verified by coronary
      angiography and compared with healthy controls. Patients were observed before
      percutaneous transluminal coronary angioplasty (21 patients: one with artery
      disease, nine with 2- or 3-artery disease, and five with restenosis). RESULTS AND
      CONCLUSIONS: Decreased tryptophan concentrations were found in a significant
      proportion of coronary heart disease patients and coincided with increased kyn
      trp-1 and also with increased neopterin concentrations, indicating an activated
      cellular immune response. We conclude that in coronary heart disease immune
      activation is associated with an increased rate of tryptophan degradation and
      thereby lowered tryptophan levels. Results may provide a basis for a better
      understanding of the pathogenesis of mood disturbances and depression in coronary
      heart disease patients.

PMID- 12814391
TI  - Expression of matrix metalloproteinase-9 in mononuclear cells of
      hyperhomocysteinaemic subjects.
AB  - Atherosclerotic plaque instability and rupture requires extracellular matrix
      modification, a complex process regulated by matrix metalloproteinases (MMPs). We
      hypothesized that homocysteine's atherogenic effects may involve MMP-mediated
      mechanisms. Our results showed the following: (i) Compared with healthy control
      subjects (n = 9), patients with hyperhomocysteinaemia (n = 9) had elevated mRNA
      levels of MMP-9 and tissue inhibitors of metalloproteinases-1 (TIMP-1) in freshly
      isolated peripheral blood mononuclear cells (PBMCs), which were positively
      correlated with homocysteine and negatively correlated with folate and vitamin
      B12 levels. (ii) Peripheral blood mononuclear cells obtained from these patients
      released markedly enhanced the amount of MMP-9 upon oxidized LDL (oxLDL)
      stimulation, whereas no such enhancing effect was seen in cells from healthy
      controls. (iii) During folic acid 6 weeks' treatment, normalization of
      homocysteine levels was accompanied by a significant reduction in mRNA levels of
      MMP-9 and TIMP-1 in PBMCs, as well as a marked reduction in oxLDL-stimulated
      release of MMP enzyme activity. These novel findings may suggest that
      homocysteine exerts its atherogenic effect in part by elevating levels and
      activity of MMPs, which in turn may enhance matrix degradation, potentially
      promoting atherogenesis and plaque instability. Moreover, our findings suggest
      that folic acid supplementation may down-regulate these inappropriate responses
      in these patients.

PMID- 12814392
TI  - Fibrinogen, inflammation and concentric left ventricular hypertrophy in chronic
      renal failure.
AB  - BACKGROUND: We investigated the relationship between fibrinogen and
      echocardiographic measurements of left ventricular (LV) geometry and LV function
      in a group of 192 patients with end stage renal disease (ESRD). RESULTS: Patients
      in the third fibrinogen tertile had higher mean wall thickness (MWT), relative
      wall thickness (RWT) and left ventricular mass index (LVMI) and lower LV end
      diastolic diameter and LV ejection fraction than those in the other tertiles. On
      multivariate analysis fibrinogen resulted to be an independent correlate of MWT
      (P = 0.001) and RWT (P = 0.0001) and the first factor in rank explaining the
      variance in LV ejection fraction (P = 0.0001). Left ventricular concentric
      hypertrophy was more prevalent (P = 0.001) in patients in the third fibrinogen
      tertile (n = 35, 54%) than in those in the second (n = 24, 37%) and first (n =
      13, 21%) tertiles. In a multiple logistic regression model patients in the third
      tertile of fibrinogen had a risk for left ventricular concentric hypertrophy that
      was 3.56 (95% CI: 1.56-8.14) fold higher than in those in the first tertile (P =
      0.003). CONCLUSIONS: Elevated fibrinogen is independently associated with LV
      concentric hypertrophy and systolic dysfunction in ESRD patients. These
      relationships may contribute to the negative prognostic impact of elevated
      fibrinogen levels in ESRD.

PMID- 12814393
TI  - Impaired vasodilator responses to atrial natriuretic peptide in essential
      hypertension.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) has vasodilating and
      diuretic/natriuretic properties, both of which contribute to lower blood
      pressure. These effects are mediated by binding of ANP to a cell-surface receptor
      [type A guanylyl cyclase (GC-A)]. It has been demonstrated by studies in
      monogenetic mouse models that the ANP/GC-A system participates in the maintenance
      of blood pressure homeostasis. METHODS: In male patients with essential
      hypertension (EH; n = 36) as the only cardiovascular risk factor and normotensive
      controls (n = 12), blood flow was measured in the forearm circulation in response
      to i.a. infusion of synthetic human ANP, acetylcholine, orciprenaline, and sodium
      nitroprusside by strain-gauge venous plethysmography. In blood samples, cyclic
      guanosine'5-monophosphate (cGMP) and ANP concentrations were measured at resting
      conditions and during exogenous ANP infusion. In 200 patients with EH, genomic
      DNA was screened for an inhibitory deletion mutation of the GC-A gene, which has
      been recently linked to EH in a Japanese cohort. RESULTS: The vasodilatations in
      response to ANP and acetylcholine were impaired in the forearm circulation of
      patients with EH, whereas the responses to orciprenaline and nitroprusside were
      preserved. Plasma ANP and cGMP concentrations were increased in the patients with
      EH both at resting conditions and during ANP infusion; the resting plasma cGMP
      levels correlated significantly with the plasma ANP levels (r = 0.68). A specific
      deletion mutation of the GC-A gene did not account for the diminished relaxant
      effects of ANP in our study population. CONCLUSIONS: The vascular ANP/GC-A
      pathway is altered in patients with EH, in addition to the known defects on the
      nitric oxide/cGMP pathway. Attenuation of the vasodilative responses to ANP
      suggests impaired receptor or postreceptor responsiveness of GC-A. It is possible
      that this dysfunction participates in the pathomechanism of EH.

PMID- 12814394
TI  - Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.
AB  - BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) is a
      ligand-activated transcription factor known to be central to both adipose tissue
      development and insulin action. Growth of adipose tissue requires differentiation
      of preadipocytes with acquisition of specific cellular functions including
      insulin sensitivity, leptin secretion and the capacity to store triglyceride.
      Dietary fatty acids and members of the thiazolidinedione class of compounds have
      been reported to influence adipogenesis at the transcriptional level. Here, we
      compare the effects of a dietary fatty acid, linoleic acid, and a
      thiazolidinedione, rosiglitazone, on biochemical and functional aspects of human
      preadipocyte differentiation in vitro. MATERIALS AND METHODS: Human omental and
      subcutaneous preadipocytes were subcultured 2-3 times and subsequently
      differentiated for 21 days in the presence of either linoleic acid or
      rosiglitazone. Differentiation was assessed using a number of biochemical and
      functional parameters. RESULTS: Omental and subcutaneous preadipocytes
      differentiated in the presence of linoleic acid showed marked cytoplasmic
      triacylglycerol accumulation however, no biochemical markers of differentiation
      (LPL expression, G3PDH gene expression and enzyme activity and leptin expression
      or secretion) were detected. In contrast, treatment of these cells with
      rosiglitazone induced full biochemical differentiation as judged by all markers
      assessed, despite comparatively little lipid accumulation. The rosiglitazone
      effects were subcutaneous depot-specific. Cells treated with linoleic acid showed
      decreased glucose uptake cf rosiglitazone-treated cells. A luciferase reporter
      assay demonstrated that rosiglitazone potently activates h-peroxisome
      proliferator activated receptor gamma while linoleic acid had no effect.
      CONCLUSIONS: These studies demonstrate that (a) human preadipocytes have the
      potential to accumulate triacylglycerol irrespective of their stage of
      biochemical differentiation; (b) while omental preadipocytes are refractory to
      biochemical differentiation in vitro, they are able to accumulate
      triacylglycerol; and (c) rosiglitazone and linoleic acid may exert their effects
      via different biochemical pathways.

PMID- 12814395
TI  - Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type
      II diabetes mellitus.
AB  - BACKGROUND: In diabetic patients, impairment of the cardiovagal limb of the
      baroreflex has been well established. However, the role of sympathetic mediated
      baroreflex vasomotor control of the blood vessels is not well defined. We
      therefore assessed the vasomotor responses to sinusoidal baroreceptor stimulation
      in diabetic patients. MATERIALS AND METHODS: We studied 14 type II diabetic
      patients (age; 57 +/- 7 years) and 18 healthy controls (age; 59 +/- 11 years).
      Oscillatory neck suction was applied at 0.1 Hz to assess the sympathetic
      modulation of the heart and blood vessels, and at 0.2 Hz to assess the effect of
      parasympathetic stimulation on the heart. Breathing was paced at 0.25 Hz.
      Spectral analysis was used to evaluate the oscillatory responses of RR-interval
      and blood pressure. RESULTS: The diabetic patients showed a significantly lower
      RR-interval response (P < 0.05) to the 0.1 Hz neck suction (2.52 +/- 0.50-3.62 +/
      0.54 ln ms2) than the controls (4.23 +/- 0.31-6.74 +/- 0.36 ln ms2). The
      increase in power of 0.1 Hz systolic blood pressure oscillations during 0.1 Hz
      suction was also significantly smaller (P < 0.05) in the diabetics (1.17 +/- 0.44
      1.69 +/- 0.44 mmHg2) than in the controls (1.60 +/- 0.29 mmHg2-5.87 +/- 1.25
      mmHg2). The magnitude of the peak of the 0.2 Hz oscillation in the RR-interval in
      response to 0.2 Hz neck stimulation was significantly greater (P < 0.05) in the
      controls (3.42 +/- 0.46 ln ms2) than in the diabetics (1.58 +/- 0.44 ln ms2).
      CONCLUSION: In addition to cardiovagal dysfunction, baroreflex-mediated
      sympathetic modulation of the blood vessels is impaired in type II diabetic
      patients.

PMID- 12814396
TI  - Decreased cortisol production in male type 1 diabetic patients.
AB  - BACKGROUND: It is unclear whether cortisol production and the 11betaHSD-mediated
      cortisol to cortisone interconversion are different between type 1 diabetic
      patients and healthy subjects. MATERIALS AND METHODS: Fourteen male, nonobese,
      normotensive type 1 diabetic patients without severe complications (HbA1c < 8.5%)
      were studied twice during a daily sodium intake of 50 and 200 mmol, and were then
      compared with 14 individually matched healthy subjects. Cortisol production was
      assessed by the sum of urinary cortisol metabolite excretion. Urinary ratios of
      (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydro-cortisone [(THF + allo
      THF)/THE] and of free cortisol/free cortisone [UFF/UFE] were determined as
      parameters of 11betaHSD activity. RESULTS: Sum of urinary cortisol metabolite
      excretion during low- and high-salt diet was 7.4 +/- 2.5 vs. 7.7 +/- 2.3 nmol min
      1 m-2 (NS) in diabetic patients and 9.7 +/- 2.1 vs. 11.2 +/- 4.1 nmol min-1 m-2
      (NS) in healthy subjects, respectively (P < 0.05 vs. healthy subjects at both
      diets). The allo-THF excretion and allo-THF/THF ratios were lower in the diabetic
      than in the healthy males during both diets (P < 0.05). Urinary (THF +
      alloTHF)/THE and UFF/UFE were similar in both groups and remained unchanged after
      salt loading. CONCLUSIONS: The sum of urinary cortisol metabolite excretion as a
      measure of cortisol production is lower in nonobese, normotensive type 1 diabetic
      males with adequate glycaemic control and without severe complications,
      irrespective of sodium intake. We suggest that this is at least in part as result
      of diminished 5alpha reductase activity, resulting in a decreased cortisol
      metabolic clearance. In type 1 diabetic and in healthy males, the 11betaHSD
      setpoint is not affected by physiological variations in sodium intake.

PMID- 12814397
TI  - Alternative sources of beta cells for cell therapy of diabetes.
AB  - Type 1 and type 2 diabetes affect 150 million people worldwide. This is a result
      of the incapacity of pancreatic beta cells to produce and secrete enough insulin.
      Transplantation of pancreatic beta cells represents a potential therapeutic
      approach for type 1 diabetes. However, one limitation is the insufficient amount
      of beta cells available for grafts. Alternative sources of beta cells have yet to
      be defined. During the past years, progress has been made in the definition of
      new strategies to produce mature pancreatic beta cells. Different cell sources
      are currently tested for their capacity to differentiate into mature beta cells.
      In this review, I will summarize the status of our knowledge in the field of cell
      therapy for diabetes.

PMID- 12814398
TI  - Low mast cell density in the human duodenal mucosa from chronic inflammatory
      duodenal bowel disorders is associated with defective villous architecture.
AB  - BACKGROUND: Mast cells (MC) have recently been implicated in the processes of
      tissue homeostasis, remodeling and repair. DESIGN: In this study, the total and
      tryptase-reactive mast cell populations were quantified in the duodenal mucosa of
      27 subjects suffering from chronic inflammatory bowel disorders. Mast cell
      density was both related to the general villous architecture (normal or
      defective) and to the microvascular density in the duodenal mucosa. RESULTS:
      Total mast cell and tryptase-positive mast cell subpopulation densities were
      found to be significantly reduced in the samples with defective villous
      architecture in comparison with those exhibiting a normal villous profile. In
      these last samples, a relevant proportion of mucosal mast cells exhibited
      ultrastructural features of secretory activity, in particular piecemeal
      degranulation. Finally, no correlation was established between microvascular
      density and tryptase activity, as it has been previously demonstrated in other
      pathological conditions. CONCLUSIONS: Overall, these findings indicate a
      significant correlation between mast cell density and the duodenal mucosal
      architecture.

PMID- 12814399
TI  - Numbers of colony-forming progenitors in patients with systemic mastocytosis:
      potential diagnostic implications and comparison with myeloproliferative
      disorders.
AB  - BACKGROUND: An increase in colony-forming progenitor cells (CFU) is typically
      seen in myeloproliferative disorders (MPD). Systemic mastocytosis (SM) is a
      haemopoietic neoplasm involving myeloid progenitors similar to MPD. In the
      present study, we measured the levels of peripheral blood (pb) and bone marrow
      (bm) CFU in patients with different categories of SM, and compared them with
      those obtained in MPD patients and healthy controls. MATERIALS AND METHODS:
      Numbers of CFU (CFU-GM, BFU-E, CFU-GEMM) were measured in a colony assay in 25
      patients with SM [indolent SM (ISM), n = 15; smouldering SM (SSM), n = 3; SM with
      an associated haematologic clonal non-mast cell lineage disease (SM-AHNMD), n =
      5; aggressive SM (ASM), n = 1; mast cell leukaemia (MCL), n = 1] and 37 with MPD
      [chronic myeloid leukaemia (CML), n = 10; polycythemia vera (PV), n = 8;
      essential thrombocytosis (ET), n = 9; idiopathic myelofibrosis (IMF), n = 10].
      RESULTS: In the patients with MPD, elevated numbers of pb CFU were detected in
      all groups when compared with healthy controls (P < 0.05). In most of the
      patients with ISM, circulating CFU levels (CFU-GM, BFU-E, and CFU-GEMM) were
      within the normal range. In SSM, pb CFU-GM levels were normal in two patients,
      and elevated in a third patient. In the "SM-AHNMD-group", CFU levels were found
      to reflect the nature of the AHNMD: in SM with concomitant acute myeloid
      leukaemia (SM-AML, n = 2), the levels of CFU were low or undetectable, whereas in
      SM with chronic myelomonocytic leukaemia (SM-CMML, n = 2), elevated numbers of pb
      CFU-GM were found. CONCLUSION: The numbers of CFU are normal in patients with
      ISM, but elevated in some patients with SSM and SM-CMML. An elevated CFU level in
      SM should raise the suspicion of an associated MPD (CMML) or smouldering SM, a
      novel SM-subtype that shares several features with MPD and sometimes progresses
      to an overt SM-MPD.

PMID- 12814400
TI  - Recovery of T-cell subsets after antiretroviral therapy in HIV-infected children.
AB  - BACKGROUND: Variation of percentageCD4+ T cells may accurately reflects the
      kinetics of a comprehensive immune recovery independently of the antiretroviral
      (ART) regimen. To test this we have investigated the relationship among
      peripheral blood T-cell subsets with the variation of percentageCD4+ T cells
      during follow up in 49 HIV-infected children. METHODS: Children were divided into
      two groups according to the sign of slope percentageCD4+ T cell during follow up:
      Ps-group (positive slope) and Ns-group (negative percentageCD4 slope) indicative
      of immunological recovery or not, respectively. CD4+ and CD8+ T-cell subset
      percentages were examined by three-colour flow cytometry. RESULTS: We found
      higher memory CD4+ and CD8+ T-cell percentages in the Ns-group than in the Ps
      group, and inversely, higher naive CD4+ and CD8+ T cells in the Ps-group than in
      the Ns-group. CD4+ and CD8+ subsets in the Ps-group expressed higher levels of
      CD38+ and lower levels of HLA-DR+ compared with the Ns-group. We found a very
      strong positive correlation among the slope of percentageCD4+, CD4+ CD38+,
      whereas a negative correlation among the slope of percentageCD4+, the CD8+ CD28+
      CD57+ and CD8+ CD57+ T-cell subsets. CONCLUSION: Recovery of the CD4+ T-cell
      percentage induced by ART reflects a reduction in the chronic immune activation
      and a measurable reconstitution of the immune system and depends on naive CD4+ T
      cells.

PMID- 12814401
TI  - Interleukin-2 has no additional therapeutic efficacy in the retreatment of
      patients with chronic hepatitis C that had not responded to interferon-alpha plus
      ribavirin.

PMID- 12814403
TI  - Obstructed defecation.
AB  - BACKGROUND: In the last decade our understanding of pelvic floor function and
      dysfunction has improved significantly. A more rational diagnostic and
      therapeutic approach is now possible for the group of patients with constipation
      due to obstructed defecation (OD). METHODS: The review is based on a literature
      search using the PubMed database focusing mainly on recent literature addressing
      the subject. RESULTS: Obstructed defecation occurs in about 7% of the adult
      population. Different pathophysiological mechanisms, either functional or
      anatomical, eventually lead to OD. Different tests (defecography, balloon
      evacuation test, manometry, electromyography, colonic transit time
      measurementmanometry) play an important role to quantify the problem. These tests
      are not without problems as abnormal results are also found in asymptomatic
      controls. Also, there is poor agreement between different tests and a poor
      correlation with symptomatology. Thus, for most syndromes conservative treatment
      including biofeedback is appropriate. Surgery can yield excellent results in
      selected cases. CONCLUSION: Validation of scoring systems and quantitative tests
      is still needed. More uniform and strict criteria for anismus should be applied
      to make therapeutic approaches comparable. Appropriate selection of patients for
      surgery is the key to success.

PMID- 12814404
TI  - Chronic idiopathic slow transit constipation: pathophysiology and management.
AB  - OBJECTIVE: Patients with idiopathic slow-transit constipation comprise a small
      proportion of the total population complaining of constipation. The purpose of
      this review is to present an update of pathophysiology of this disorder and its
      application in clinical management. METHODS: Medline was used to search English
      language articles published up to the end of September 2002 on the subject of
      slow-transit constipation. RESULTS AND CONCLUSIONS: Patients with idiopathic slow
      transit constipation can be divided into 2 subgroups: 1. patients with normal
      proximal gastrointestinal motility and with onset of constipation in connection
      with childbirth or pelvic surgery. This subgroup may benefit from consideration
      of surgical treatment; 2. patients who have a dysfunctional enteric
      nervous/neuroendocrine system and exhibit colonic dysmotility as part of a
      generalised gastrointestinal dysmotility. Surgical approach in this subgroup
      seems to be unhelpful and medical treatment appears to be a better approach.

PMID- 12814405
TI  - Recent randomised trials in colorectal disease.
AB  - Progress in colorectal surgery over the last few years is evident by the growing
      number of randomised controlled trials reported. We have scrutinised such trials
      reported over the last year across the entire spectrum of colorectal disease and
      have presented the significant findings in this trials report.

PMID- 12814406
TI  - Stapled haemorrhoidopexy: a consensus position paper by an international working
      party - indications, contra-indications and technique.
AB  - An international working party with experience in the performance of an
      alternative haemorrhoid operation through the use of the circular stapler was
      convened for the purpose of developing a consensus as to the criteria for
      undertaking this procedure. The agenda consisted of first, naming the operation;
      second, the indications and contra-indications for its performance; and third,
      the preferred surgical technique. Among the recommendations for individuals who
      plan to embark on this surgery are that experience with anorectal surgery and an
      understanding of anorectal anatomy are requisites; experience with circular
      stapling devices is essential; and the surgeon must attend a formal course which
      should include lectures, videos, the application of the instrument in models, and
      observation of the operation as performed by a surgeon recognized by his or her
      peers-leading ultimately to undertaking the procedure while being observed by an
      experienced surgeon. Following satisfactory completion of the above, independent
      responsibility should be determined by an individual's department of surgery.

PMID- 12814407
TI  - Results following conservative lateral sphincteromy for the treatment of chronic
      anal fissures.
AB  - INTRODUCTION: Lateral sphincterotomy is now the standard surgical treatment for
      fissure-in-ano. Healing is achieved in 90% of cases, however, sphincterotomy also
      carries a significant risk of incontinence. Traditional sphincterotomy comprises
      of division of the internal sphincter up to the level of the dentate line, a more
      conservative division could lead to a lower incontinence rate, with an equivalent
      healing rate. MATERIALS AND METHODS: A total of 65 patients undergoing
      conservative lateral sphincterotomy under a single operator between January, 1996
      and January, 2002 were reviewed. Specific questions were asked regarding overall
      success of the operation, leakage of fluid, faeces or flatus and recurrence of
      fissure symptoms. Supplemental data was obtained from a retrospective analysis of
      the patients' case notes to ascertain demographics, length of hospital stay and
      complication rate. RESULTS: Sixty of 65 patients responded to our postal
      questionnaire. The male to female ratio was 1:1 and the mean age 40.3 years of
      age. No complications were recorded and 97% of patients had achieved fissure
      healing by the time of their out-patient follow-up (mean 6.9 weeks). Two patients
      reported new incontinence following their procedure; one patient experienced
      incontinence of fluid and flatus (1.7%) and the remaining patient complained of
      incontinence to flatus only. No patients experienced incontinence of faeces.
      Eleven patients experienced persistent symptoms of pain and bleeding but only 6
      of these patients required treatment from their general practitioner which
      consisted of stool softeners and topical analgesia. No patients required re
      operation. CONCLUSION: A conservative division of the internal anal sphincter
      results in adequate fissure healing and a much lower incontinence rate than that
      previously recorded in the literature for more traditional divisions of the
      internal anal sphincter.

PMID- 12814408
TI  - Pathological subgroups may predict complications but not late failure after ileal
      pouch-anal anastomosis for indeterminate colitis.
AB  - INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) for indeterminate colitis
      (IndC) may lead to an increased risk of perineal complications and pouch loss.
      This study evaluated pathological subgroups of IndC to identify a predictor of
      increased complication rates after IPAA for IndC. PATIENTS AND METHODS: Of 171
      IPAAs with a postoperative diagnosis of IndC, IndC was confirmed in 115 of the
      140 specimens available for re-examination. These were divided into IndC
      favouring ulcerative colitis (Group I; n = 99), 'true' IndC (Group II; n = 8),
      and IndC favouring Crohn's (Group III; n = 8). 61 presented with fulminant
      colitis. Patients in Group I were subdivided into having (A) deep ulcers (B)
      transmural lymphoid aggregates (C) skip lesions (D) terminal ileal inflammation
      and/or (E) a caecal patch. Outcome was determined by chart analysis, and compared
      to 231 randomly selected patients with IPAA for ulcerative colitis (UC) matched
      for age, gender, and follow-up. RESULTS: Only patients with evidence of deep
      ulceration (Group IA) had a significant increase in the incidence of Crohn's
      disease (4.3%vs. 0.43%, P = 0.04), complex perianal fistulae (4.3%vs. 0.43%, P =
      0.04), and pelvic abscess (12.9%vs. 2.2%, P < 0.001). No pathological subgroup of
      IndC patients had a significantly different rate of pouch failure or pouch loss.
      CONCLUSIONS: Pathological stratification may predict those more likely to develop
      Crohn's disease or other complications, but not pouch failure. On this basis, we
      feel that patients with IndC should not be precluded from having IPAA surgery.

PMID- 12814409
TI  - Diverticular disease has an impact on quality of life -- results of a preliminary
      study.
AB  - OBJECTIVE: Diverticular disease (DD) is common in the western world, and carries
      a significant morbidity. Although patients can have long standing symptoms no
      research on quality of life (QoL) in DD exists in the literature. Assessment of
      QoL may be useful in decision making and selection of patients who would be
      appropriate candidates for elective surgical treatment. The aim of this study was
      to examine whether DD has an impact on QoL. MATERIALS AND METHODS: A combination
      of structured interview and questionnaire survey was performed. One hundred
      people were divided into two groups: Group A, 50 patients with symptomatic DD as
      their primary diagnosis; Group B, A control group of 50 healthy volunteers. A
      structured QoL questionnaire, examining bowel symptoms, systemic symptoms,
      emotional symptoms and social function, was completed by the subjects in both the
      patient and the control group. RESULTS: In the patient group scores fell well
      below the optimum QoL scores in each of the subscales particularly in the areas
      of bowel symptoms (43.8 vs 65.4 for controls) and emotional function (55.1 vs
      75.9 for controls). Patients with DD had statistically significantly lower QoL
      scores than controls and this difference was consistent in all four examined
      areas (P < 0.003 for all categories). CONCLUSION: Our preliminary study suggests
      that DD does affect a person's QoL. The authors recommend that further research
      is required in the development of a (QoL) scoring system specific for patients
      with diverticular disease. Having developed a tool that can accurately measure
      the subjective health status (QoL) of this disease group we will then be able to
      develop a more systematic approach to the delivery of treatment, management and
      care of patients with diverticular disease.

PMID- 12814410
TI  - Effects of intraperitoneal 4% icodextrin solution on the healing of bowel
      anastomoses and laparotomy incisions in rabbits.
AB  - OBJECTIVE: Peri-operative lavage and postoperative instillation of a 4%
      icodextrin solution reduces de novo formation and reformation of peritoneal
      adhesions following abdominal surgery. This experimental study evaluated the
      effects of 4% icodextrin treatment on the healing of bowel anastomoses and
      laparotomy incisions. MATERIALS AND METHODS: Female New Zealand White rabbits
      (weight 2.21-2.77 kg) were randomised by ascending weight to one of 3 surgical
      treatments, each with 2 termination points (6 groups of 8 animals). The
      treatments were anastomotic bowel surgery alone or with lavage and postoperative
      instillation of either 4% icodextrin solution or Lactated Ringer's Solution
      (LRS). The solutions were coded A and B by the supplier, so that the study
      personnel were blinded to their identity. After the abdomen was opened, 30 ml of
      solution A or B was instilled and removed by aspiration prior to surgery. The
      ascending colon was then transected 5 cm aboral to the ileocaecal junction and
      the ends anastomosed. During surgery, 5 ml of the solution was applied 4 times at
      the surgical site, and a further 30 ml was administered and aspirated as a
      postoperative lavage. Just prior to closure of the abdominal wall, 50 ml of the
      solution was administered as a postoperative instillate. Duplicate treatment
      groups were terminated 7 and 21 days after surgery and the anastomotic sites
      inspected for adhesion and/or abscess formation. In 6 animals per group, an 8-12
      cm length of colon including the anastomotic site was removed for measurement of
      bursting pressure, and a section of the abdominal wall including the incision
      line was tested for breaking strength. The other 2 animals per group provided
      tissue for histological analysis of wound healing at the bowel and incision
      sites. RESULTS: There was no significant difference between the 3 treatment
      groups for any parameter (P > 0.05). Compared with the surgical control at either
      day 7 or 21 after surgery, the administration of solutions A or B did not affect
      the formation of abscesses or adhesions, the bursting strength of the bowel, or
      the tear strength of the abdominal wall incision. Histological assessment of the
      quality of wound healing showed no differences between treatment groups in
      inflammatory cell infiltration, fibroblast density, blood vessel formation or
      collagen maturity. CONCLUSIONS: The use of a 4% icodextrin solution for peri
      operative lavage and postoperative instillation in a rabbit model of bowel
      anastomotic healing did not result in any difference from either LRS treated or
      untreated surgical controls.

PMID- 12814411
TI  - The incidence and causes of permanent stoma after anterior resection.
AB  - AIMS: Defunctioning stomas are used following anterior resection to guard against
      the serious consequences of anastomotic leak such as pelvic sepsis and
      generalized peritonitis. This study aims to determine what proportion of patients
      undergoing anterior resection have a defunctioning stoma, how many of these
      patients do not have their stoma closed, and the reasons for this. METHODS: All
      patients undergoing a resection for rectal cancer in our institution in a five
      year period (January 1995 to December 1999) are included in the study. Anterior
      resection was performed on 154 patients, divided into 76 anterior resections (AR)
      and 78 low anterior resections (defined as the anastomosis within 6 cm of the
      anal verge). The data from these patients were analysed retrospectively. RESULTS:
      Of the total of 154 patients undergoing anterior resection, 59 (38%) were
      defunctioned, divided into 33 with loop ileostomy and 26 with loop colostomy.
      Five of these patients had not had their stoma closed at a median follow up of
      four years (range 1.5-6.5 years). The reasons for non closure were anastomotic
      stricture (2), metastatic disease (2), and patient choice (1). When comparing AR
      and LAR, 16% of patients had a defunctioning stoma after AR, compared with 60%
      after LAR (P < 0.01). CONCLUSION: Anterior resection is being performed for very
      low rectal tumours in order to avoid a permanent stoma. However we have found
      that 8% of patients who are defunctioned with a stoma at anterior resection will
      not have their stoma closed, and conclude that patients should be warned of this
      pre-operatively.

PMID- 12814412
TI  - Neoadjuvant antiangiogenic therapy with tamoxifen does not impair
      gastrointestinal anastomotic repair in the rat.
AB  - INTRODUCTION: Antiangiogenic therapy has the potential to moderate tumour and
      micrometastatic growth. Its use in the perioperative period is attractive but its
      potential to compromise wound and anastomotic healing is a cause for concern.
      Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound
      healing. We hypothesised that tamoxifen would not adversely affect skin wound and
      gut anastomotic healing. METHODS: A previously established model of tamoxifen,
      administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was
      used. Animals received two days pretreatment prior to laparotomy and small bowel
      anastomosis. Treatment was continued until completion of the study. The principal
      outcome measures are survival, macroscopic wound and anastomotic healing,
      anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP)
      content. RESULTS: Tamoxifen treated animals had fewer complications of skin wound
      healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was
      no significant difference in adhesion formation or macroscopic complications of
      anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen
      treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P <
      0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs.
      127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly
      less than placebo controls from postoperative day 3 with no difference in
      mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma
      OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs.
      1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03). CONCLUSION: Antiangiogenic
      therapy with tamoxifen has no demonstrable adverse effects on wound or
      anastomotic repair and its perioperative use is compatible with successful early
      surgical outcomes.

PMID- 12814413
TI  - A study of the complications and pelvic visceral function after restorative
      proctocolectomy and W pouch construction.
AB  - OBJECTIVE: Aspects of ileal pouch surgery remain controversial. The authors'
      single practice experience of 107 operations illustrates many of them. It was
      hoped that its study would contribute usefully to the debate. PATIENTS AND
      METHODS: Details of all 107 restorative proctocolectomies carried out since the
      operation was started in Gloucester in 1984 until the study period ended have
      been kept prospectively. All patients had proctectomy by mesorectal dissection,
      and 106 had W pouch restoration. Four suffered functional failure requiring
      reversion to ileostomy and three patients have died. The remaining 99 were sent a
      questionnaire concerning pelvic visceral function and evidence of pouchitis.
      Records of all but one of the patients have been reviewed. RESULTS: Surgical
      morbidity was low with neither chronic pelvic sepsis, pouch related fistula,
      pouch haemorrhage nor pouch ischaemia. Mucosectomised patients had similar bowel
      control to the stapled group. The policy change from routine to selective
      protective ileostomy proved satisfactory. W pouch function was found to be
      comparable to that reported from major J pouch series, although anti-diarrhoeal
      usage was reduced, and was not influenced by either gender, age or time since
      surgery. CONCLUSION: None of the following reasonably intuitive assumptions seem
      supported by our findings: that mesorectal excision necessarily poses a greater
      danger to pelvic visceral function than close rectal dissection, that the greater
      capacity of W pouches will be reflected in markedly less frequency, that
      mucosectomy would impair anal control, or that a defunctioning ileostomy is a
      mandatory precaution. Pouch frequency is less if wind can be passed separately;
      otherwise functional outcome seems determined by other, non-technical, factors.

PMID- 12814414
TI  - Short-term pre-operative smoking cessation intervention does not affect
      postoperative complications in colorectal surgery: a randomized clinical trial.
AB  - BACKGROUND: Smokers have a higher risk of complicated tissue and wound healing
      after surgery than nonsmokers. We tested the hypothesis that short-term pre
      operative cessation of smoking in colorectal surgery decreases the incidence of
      postoperative tissue and wound complications. METHODS: From February 1998 to
      March 2001, 60 patients, who smoked daily, undergoing colorectal resection were
      randomly assigned 2-3 weeks before scheduled surgery to either abstinence from
      smoking, counselling and nicotine replacement therapy or maintenance of daily
      smoking habits. Postoperative tissue and wound complications necessitating
      surgical or medical treatment were evaluated at discharge and 30 days after
      surgery by blinded outcome assessment. RESULTS: In the pre-operative period of 15
      days (8-24) (median, interquartile range (IQR)), 89% of the patients in the
      intervention group vs. 13% in the control group abstained from smoking or reduced
      by more than half (P < 0.05). In the postoperative period of 11 days (10-13), the
      corresponding figures were 92% and 50%, respectively (P < 0.05). Postoperative
      tissue and wound complications occurred in 33% (9 of 27) of the patients in the
      intervention group compared to 27% (8 of 30) in the control group (NS). Likewise,
      no difference in overall postoperative complication rate was found between the
      groups. CONCLUSION: Short-term cessation of smoking does not reduce the risk of
      complicated tissue and wound healing or other complications in colorectal
      surgery.

PMID- 12814415
TI  - Angiogenesis in anal warts, anal intraepithelial neoplasia and anal squamous cell
      carcinoma.
AB  - INTRODUCTION: Most cases of anal carcinoma seem to develop from high grade anal
      intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre
      invasive epithelial genital lesions (e.g. those of the cervix and vulva) have
      been shown to be associated with increased angiogenesis. In this study we
      examined biopsies of anal lesions ranging from warts to invasive anal carcinoma,
      with the aim of assessing the degree of angiogenesis in pre-invasive anal
      lesions. METHOD: Samples from 70 patients (51 male) who had undergone excision
      biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN
      (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from
      normal HIV-anal skin were used as controls. The samples were stained for von
      Willebrand factor, a specific marker of endothelial cells. Angiogenesis was
      measured by microvessel density (MVD) analysis, quantifying the microvessels in
      the stroma adjacent to the epithelial lesion. RESULTS: There was a statistically
      significant (P < 0.001) progressive increase in MVD between low grade AIN, high
      grade AIN and anal SCC. The difference in MVD between normal skin, warts and low
      grade AIN was not statistically significant. CONCLUSION: There are progressive
      abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those
      found in cervical and vulvar pathology. These findings may have biological,
      prognostic and therapeutic implications.

PMID- 12814417
TI  - The interrupted serosubmucosal anastomosis - still the gold standard.
AB  - BACKGROUND: The single-layer appositional serosubmucosal anastomosis is a well
      established technique and appears to have a favourable record. Over a 15-year
      period the senior author of this paper has performed or directly supervised 553
      anastomoses using this technique. This report describes the results of these
      operations, the results of stapled anastomoses carried out during the same period
      and discusses the utility of the handsewn technique. METHODS: From August 1986 to
      July 2001, 553 intestinal anastomoses in 550 patients were fashioned using single
      layer, interrupted serosubmucosal 3/0 braided polyamide and 131 anastomoses in
      131 patients were performed using a circular anastomosing stapler. RESULTS: One
      anastomotic leakage occurred in the group of patients whose anastomosis was
      handsewn (0.2%) and 11 leaks occurred in those who had a stapled anastomoses
      (8.4%). The mortality rate in each group was similar (2% and 2.3%, respectively).
      There were no deaths attributable to anastomotic dehiscence in either group.
      CONCLUSION: In this prospectively audited series of 553 handsewn anastomoses the
      leakage rate was 0.2%. These results compare favourably with other published
      series and continue to support a single layer of interrupted serosubmucosal
      sutures as the gold standard for anastomoses involving the large or small bowel.

PMID- 12814416
TI  - Screening the average risk population for colorectal cancer: the Israeli
      experience 1985-97.
AB  - INTRODUCTION: Five prospective, controlled trials of CRC screening, 4 of them
      randomized, using the Hemoccult test in large populations, have been reported
      from Europe and USA. In all the series stage shifting was documented, and
      mortality from CRC was reduced by 12-33%. In comparison with this large
      experience, the Israeli screening programs in the average risk population are
      very modest, started as case findings and expanded to nation-wide recommendation
      for FOBT in 1999. In this study the Israeli experience between 1985 and 1997 was
      documented. METHODS: Medline search of the last 22 years for screening programs
      in Israel was performed, as well as personal contact with all the Israeli
      investigators. Reports to the Israeli Cancer Association (ICA) were collected,
      reviewed and summarized. RESULTS: Since 1985 8 papers about faecal occult blood
      test (FOBT) and 5 papers about flexible sigmoidoscopy (SIG) screening in average
      risk population have been published. 35 685 people have been screened, 110 cases
      of CRC and 546 cases of adenoma were found. The yield of SIG was 4 times that of
      FOBT for CRC. In addition, since 1990 80 084 people were screened according to
      the reports to the ICA. Five hundred and six cases of CRC and 2714 cases of
      adenoma were found. In the only prospective, controlled study, CRC incidence and
      mortality were significantly decreased in participants of a FOBT screening
      program, an effect lasting 11 years. Refusers were more likely to be male, of
      Asian-African decent, smokers, and consumers of more coffee and less tea or dairy
      food. CONCLUSION: FOBT may protect against CRC for prolonged periods. Individuals
      who refuse FOBT have significantly higher CRC incidence and mortality rates than
      those who accept testing. The Israeli experience, thus small, supports a
      comprehensive screening campaign for early detection of CRC in Israel.

PMID- 12814418
TI  - Peri-operative radiotherapy for rectal cancer: the case for a selective pre
      operative approach - the third way.
AB  - Peri-operative radiotherapy has been used widely in addition to surgery in an
      attempt to reduce local recurrence (LR) following surgical resection of rectal
      cancer. Currently different groups follow different approaches with some
      routinely administering one weeks pre-operative radiotherapy to all cases of
      operable mobile cancer with others favouring postoperative chemoradiotherapy for
      selected high risk groups. In this review we bring together the changes in
      surgery, pathology and imaging that have occurred in recent years and together
      with the data from recent randomized pre-operative radiotherapy trials propose a
      logical and optimal way of managing rectal cancer. This third way is selective
      and pre-operative and should ensure a low rate of LR with radiotherapy reserved
      for those cases that need it.

PMID- 12814419
TI  - Seton insertion for difficult anal fistulas.

PMID- 12814420
TI  - A novel method of demonstrating rectal prolapse.
AB  - BACKGROUND: Full thickness rectal prolapse may be difficult to view in the
      outpatient setting. We present a novel method to demonstrate it using equipment
      commonly found in the Urology clinic.

PMID- 12814421
TI  - Enterocolic lymphocytic phlebitis of the right colon as a cause of massive
      gastrointestinal bleeding.

PMID- 12814422
TI  - Pilonidal sinus.

PMID- 12814429
TI  - The small intestine as a model for evaluating adult tissue stem cell drug
      targets.
AB  - Adult tissue stem cells are defined and some current controversies are discussed.
      These crucial cells are responsible for all cell production in renewing tissues,
      and play a vital role in tissue regeneration. Although reliable stem cell markers
      are generally unavailable for adult epithelial tissues, the small intestinal
      crypts are an excellent in vivo model system to study stem cells. Within this
      tissue, the stem cells have a very well-defined cell position, allowing accurate
      definition of stem cell specific events. Clonal regeneration assays for the small
      intestine allow stem cell survival and functional competence to be studied. The
      ultimate lineage ancestor stem cells are extremely efficiently protected from
      genetic damage, which accounts for the low cancer incidence in this tissue. Some
      of the regulatory networks governing stem and transit cell behaviour are
      beginning to be understood and it is postulated that p53 plays a crucial role in
      these processes.

PMID- 12814430
TI  - The cell cycle: a review of regulation, deregulation and therapeutic targets in
      cancer.
AB  - The cell cycle is controlled by numerous mechanisms ensuring correct cell
      division. This review will focus on these mechanisms, i.e. regulation of cyclin
      dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events.
      The quality checkpoints activated after DNA damage are also discussed. The
      complexity of the regulation of the cell cycle is also reflected in the different
      alterations leading to aberrant cell proliferation and development of cancer.
      Consequently, targeting the cell cycle in general and CDK in particular presents
      unique opportunities for drug discovery. This review provides an overview of
      deregulation of the cell cycle in cancer. Different families of known CDK
      inhibitors acting by ATP competition are also discussed. Currently, at least
      three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine)
      have entered clinical trials.

PMID- 12814431
TI  - Developmental changes in the inhibition of cultured rat uterine cell
      proliferation by opioid peptides.
AB  - Opioid peptides are negative regulators of cell proliferation in several organs
      including the uterus. In the present study, the ontogeny of the direct inhibitory
      action of opioid peptides on the proliferation of cultured rat uterine cells was
      investigated. Uteri of 7, 14, 21, 28, 35 and 60-day-old rats were removed in a
      sterile way. Tissue blocks were dispersed by limited digestions with trypsin and
      collagenase. Cells were cultured in enriched Dulbecco's modified Eagle's medium
      (DMEM). Treatments were present during the entire culture period. Cell densities
      of the monolayers were determined by counting the cells following trypsinization
      and trypan blue exclusion. Rat uterine mixed cell cultures grew to confluence
      within 10 days. The average population doubling time gradually increased with the
      age of animals. Epidermal growth factor (EGF) increased cell densities of
      cultures from all age groups. The oestradiol (E2)-responsiveness appeared at 21
      days of age. The effect of [D-Met2-Pro5]-enkephalinamide (ENK) was biphasic. ENK
      and [Met5]-enkephalin (OGF) decreased cell densities of both unstimulated and EGF
      stimulated cultures from 7-day-old rats to the same extent. ENK failed to act in
      14-day-old animals. From 21 days of age on, the E2- or EGF-stimulated
      proliferation was inhibited only by ENK and DAMGO, while 30 nm DPDPE, Dynorhin-A,
      OGF, [Leu5]-enkephalin, beta-endorphin, and morphiceptin were ineffective. The
      half-inhibitory concentration of ENK was 0.3 nm. The effects of ENK were
      prevented by concomitant treatment with naloxone. Our novel data demonstrate two
      different phases of the inhibitory action of opioid peptides on rat uterine cell
      proliferation during ontogeny with an insensitive interval in between.

PMID- 12814432
TI  - Cell cycle and apoptosis.
AB  - Apoptosis and proliferation are intimately coupled. Some cell cycle regulators
      can influence both cell division and programmed cell death. The linkage of cell
      cycle and apoptosis has been recognized for c-Myc, p53, pRb, Ras, PKA, PKC, Bcl
      2, NF-kappa B, CDK, cyclins and CKI. This review summarizes the different
      functions of the proteins presently known to control both apoptosis and cell
      cycle progression. These proteins can influence apoptosis or proliferation but
      different variables, including cell type, cellular environment and genetic
      background, make it difficult to predict the outcome of cell proliferation, cell
      cycle arrest or cell death. These important decisions of cell proliferation or
      cell death are likely to be controlled by more than one signal and are necessary
      to ensure a proper cellular response.

PMID- 12814433
TI  - Protein trafficking in Giardia lamblia.
AB  - Giardia, a protozoan parasite of humans and other vertebrates, is a common cause
      of intestinal disease worldwide. Besides its medical importance, Giardia is
      considered an excellent system to study the evolution of fundamental cellular
      processes because it belongs to the earliest branches of the eukaryotic lineage
      of descent. Giardia trophozoites lack organelles typical of higher eukaryotes
      such mitochondria, peroxisomes and compartments involved in intracellular protein
      trafficking and secretion, such as the Golgi apparatus and secretory granules.
      Nevertheless, the minimal machinery for protein transport and sorting is present
      in this parasite. When Giardia undergoes encystation, the biogenesis of secretory
      organelles necessary to transport cyst wall constituents to the cell surface
      takes place. Recent studies in both vegetative and encysting trophozoites have
      provided interesting information regarding the secretory pathway of this
      important human pathogen.

PMID- 12814434
TI  - Characterization of mediators of microbial virulence and innate immunity using
      the Caenorhabditis elegans host-pathogen model.
AB  - The soil-borne nematode, Caenorhabditis elegans, is emerging as a versatile model
      in which to study host-pathogen interactions. The worm model has shown to be
      particularly effective in elucidating both microbial and animal genes involved in
      toxin-mediated killing. In addition, recent work on worm infection by a variety
      of bacterial pathogens has shown that a number of virulence regulatory genes
      mediate worm susceptibility. Many of these regulatory genes, including the PhoP/Q
      two-component regulators in Salmonella and LasR in Pseudomonas aeruginosa, have
      also been implicated in mammalian models suggesting that findings in the worm
      model will be relevant to other systems. In keeping with this concept,
      experiments aimed at identifying host innate immunity genes have also implicated
      pathways that have been suggested to play a role in plants and animals, such as
      the p38 MAP kinase pathway. Despite rapid forward progress using this model, much
      work remains to be done including the design of more sensitive methods to find
      effector molecules and further characterization of the exact interaction between
      invading pathogens and C. elegans' cellular components.

PMID- 12814435
TI  - Gene expression in the tuberculous granuloma: analysis by laser capture
      microdissection and real-time PCR.
AB  - We have assessed the kinetics of host gene expression in granulomas of mice
      infected with virulent Mycobacterium tuberculosis, using an approach that
      incorporates the laser capture microdissection (LCM) and real-time PCR technology
      in conjunction with a newly derived mathematical equation. The results have
      provided evidence indicating that conventional use of whole infected lungs to
      study granuloma-specific gene expression can yield data that may not genuinely
      reflect intralesional events. Significantly, the expression of nine host genes
      known to regulate the inflammatory response to M. tuberculosis, as determined by
      real-time PCR analysis of microdissected granuloma-derived cDNAs, was
      downregulated (up to 27-fold) at around the time when the rapid growth phase of
      the bacilli in the lungs of infected mice ends. This downregulation was masked
      when whole infected lungs were used for the studies. The data suggest that the
      host immune system can adjust and respond to, or can be modulated by specific
      physiological states of the tubercle bacillus in vivo. The LCM/real-time PCR
      based system described in this study can be applied to safely and accurately
      evaluate gene expression in any lesions that can be microscopically visualized,
      including those contained in biohazardous tissues.

PMID- 12814436
TI  - Cytoplasmic bacteria can be targets for autophagy.
AB  - Autophagy is an important constitutive cellular process involved in size
      regulation, protein turnover and the removal of malformed or superfluous
      subcellular components. The process involves the sequestration of cytoplasm and
      organelles into double-membrane autophagic vacuoles for subsequent breakdown
      within lysosomes. In this work, we demonstrate that the intracellular pathogen
      Listeria monocytogenes can also be a target for autophagy. If infected
      macrophages are treated with chloramphenicol after phagosome lysis, the bacteria
      are internalized from the cell cytoplasm into autophagic vacuoles. The autophagic
      vacuoles appear to form by fusion of small cytoplasmic vesicles around the
      bacteria. These vesicular structures immunolabel with antibodies to protein
      disulphide isomerase, a marker for the rough ER. Internalization of metabolically
      arrested cytoplasmic L. monocytogenes represents an autophagic process as the
      vacuoles have double membranes and the process can be inhibited by the autophagy
      inhibitors 3-methyladenine and wortmannin. Additionally, the rate of
      internalization can be accelerated under starvation conditions and the vacuoles
      fuse with the endocytic pathway. Metabolic inhibition of cytoplasmic bacteria
      prevents them from adapting to the intracellular niche and reveals a host
      mechanism utilizing the autophagic pathway as a defence against invading
      pathogens by providing a route for their removal from the cytoplasm and
      subsequent delivery to the endocytic pathway for degradation.

PMID- 12814437
TI  - Maturation of the Coxiella burnetii parasitophorous vacuole requires bacterial
      protein synthesis but not replication.
AB  - This study examined whether protein synthesis and replication are required for
      maturation and fusogenicity of the lysosomal-like, large and spacious
      parasitophorous vacuole (PV) of Coxiella burnetii, an obligate intracellular
      bacterium. Large and spacious PV with multiple non-replicating C. burnetii were
      observed by phase microscopy in Vero cells infected at a multiplicity of
      infection of ten and treated with a bacteriostatic concentration of nalidixic
      acid or carbenicillin, antimicrobics that inhibit DNA and cell wall biosynthesis
      respectively. Conversely, large and spacious PV were not observed in cells
      treated with a bacteriostatic concentration of the protein synthesis inhibitor
      chloramphenicol. Rather, fluorescence microscopy of individual cells revealed
      multiple, acidic PV harbouring a single organism tightly bounded by a LAMP-1
      positive vacuolar membrane. These vacuoles homotypically fused to form a large
      and spacious PV upon removal of the drug. Chloramphenicol also inhibited
      trafficking of latex beads to large and spacious PV and caused mature PV to
      collapse. Collectively, these results demonstrate that C. burnetii protein
      synthesis, but not replication, is required for fusion between nascent C.
      burnetii PV and latex bead phagosomes, and also for formation and maintenance of
      large and spacious, replicative PV. However, transit of nascent PV through the
      endocytic pathway to ultimately acquire lysosomal markers appears to occur
      irrespective of Coxiella protein synthesis.

PMID- 12814438
TI  - A newborn mouse model for the study of intestinal pathogenesis of shigellosis.
AB  - Shigella infection is characterized by the induction of acute inflammation, which
      is responsible for the massive tissue destruction of the intestinal mucosa. A
      murine model would be a valuable tool for gaining a better understanding of the
      physiopathology of shigellosis and the host immune response to Shigella
      infection, but adult mice do not develop disease upon oral inoculation. We
      therefore attempted to develop a model of infection in newborn mice. Four-day-old
      mice inoculated with 50 microl of 5 x 10(9) invasive wild-type Shigella flexneri
      5a were susceptible to bacterial infection, but mice inoculated with the non
      invasive strain BS176 were not. Histologically, 4-day-old mice infected with the
      invasive strain presented intestinal lesions and inflammation similar to those
      described in patients with shigellosis. Moreover, cytokine and chemokine
      responses consistent with inflammation were observed. Lower bacterial inocula
      induced less severe intestinal damage. In contrast, 5-day-old mice inoculated
      with either the invasive or the non-invasive strain were not infected. We have
      thus established a mouse model that is suitable for the study of the pathogenesis
      of intestinal Shigella infection.

PMID- 12814440
TI  - Making tomorrow's doctors better prescribers.

PMID- 12814441
TI  - Teaching safe and effective prescribing in UK medical schools: a core curriculum
      for tomorrow's doctors.
AB  - There is a pressing need for medical graduates to be fully prepared to take on
      the responsibilities of prescribing and to be able to respond to continual
      inevitable rapid changes in therapeutics. The curricula in UK medical schools
      were greatly influenced by Tomorrow's Doctors, published by the General Medical
      Council in 1993. This has recently been updated. While it highlights the
      management of disease and use of drugs as key learning objectives, it offers
      little specific guidance. In this document we expand on these broad statements,
      provide a view of how these learning objectives might be achieved, and identify
      the key elements of a core curriculum in prescribing and therapeutics.

PMID- 12814442
TI  - Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients.
AB  - AIMS: Cough, one of the main symptoms of bronchial asthma, is a chronic airway
      inflammatory disease with functionally damaged bronchial epithelium. Recently, we
      established an animal model with cough hypersensitivity after antigen challenge
      and clearly showed the protective effect of carbocysteine in this model. This
      study was designed to investigate the clinical effect of carbocysteine for cough
      sensitivity in patients with bronchial asthma. METHODS: The effects of the two
      orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on
      cough response to inhaled capsaicin were examined in 14 patients with stable
      asthma. Capsaicin cough threshold, defined as the lowest concentration of
      capsaicin eliciting five or more coughs, was measured as an index of airway cough
      sensitivity. RESULTS: Geometric mean values of the cough threshold at run-in
      (baseline) and after 4 weeks' treatment of placebo, 1500 mg day-1 of
      carbocysteine and 45 mg day-1 of ambroxol hydrochloride were 12.8 micro M (95%
      confidence interval [CI] 5.5, 29.6), 11.0 micro M (95% CI 4.4, 27.5), 21.0 micro
      M (95% CI 8.8, 50.2) and 11.6 micro M (95% CI 5.8, 23.3), respectively. The cough
      threshold for carbocysteine was significantly greater than those of ambroxol
      hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. CONCLUSIONS:
      These findings indicate that carbocysteine administration may be a novel
      therapeutic option for asthmatic patients, especially with cough variant asthma.

PMID- 12814443
TI  - Variability of heart rate correction methods for the QT interval.
AB  - AIMS: To compare variability of heart rate-corrected QT intervals (QTc) using
      three different methods in a study of low-dose oral haloperidol. METHODS: In a
      randomized, double-blind, placebo-controlled, crossover trial, we studied QT
      interval pharmacodynamics of single doses of oral haloperidol (10 mg) in 16
      healthy subjects. Heart rate correction of the QT interval was performed using
      Bazett's, Fridericia's and subject-specific correction methods. The subject
      specific correction was performed using linear mixed modelling of placebo period
      QT vs RR data from each study subject. RESULTS: The subject-specific correction,
      in the form of QTc = QT/RRalpha, yielded a correction term alpha (slope of the
      log-transformed QT vs RR relationship) that ranged from 0.23 to 0.38 in
      individual subjects, i.e. the fixed correction term alpha = 0.5 of Bazett's
      correction was outside and the fixed correction term alpha = 0.33 of Fridericia's
      correction inside the range of individual values. The mean absolute slope of the
      QTcvs RR regression line using the subject-specific correction was significantly
      lower than the mean slopes obtained using either Bazett's or Fridericia's
      corrections. All three methods revealed a statistically significant greater mean
      QTc on haloperidol than on placebo at 10 h post-drug administration. The mean QT
      (95% CI) was 421.6 (410.8, 432.4), and 408.4 (398.6, 417.8) on haliperidol and
      placebo, respectively, using the subject-specific correction method (P = 0.0053).
      The mean QTc (95% CI) was 425.4 (414.3, 436.5) and 403.1 (394.3, 411.9) on
      haliperidol and placebo, respectively, using Bazett's correction (P = 1.7 x 10-5)
      and 423.1 (412.6, 433.6) and 408.2 (398.6, 417.8) on haliperidol and placebo,
      respectively, using Fridericia's correction (P = 7.7 x 10-4). Raw P-values were
      calculated using a paired t-test. Bonferroni-corrected P-values were calculated
      by multiplying the raw P-values by 13. CONCLUSION: Haloperidol caused a
      statistically significant mean QTc prolongation using the three correction
      methods. The QTc intervals were less dependent on RR intervals using the subject
      specific method, thus decreasing the possibility of over- or under-correction.
      The interindividual QTc changes from baseline varied significantly depending on
      the method of correction used.

PMID- 12814444
TI  - Central nervous system effects of moxonidine experimental sustained release
      formulation in patients with mild to moderate essential hypertension.
AB  - OBJECTIVES: The primary aim was to demonstrate that moxonidine, given in an
      experimental sustained release (SR) formulation, had no clinically relevant
      central nervous system (CNS) effects after 4 weeks of treatment. A clinically
      relevant CNS effect was predefined as more than 45 degrees s-1 reduction in
      saccadic peak velocity (SPV), corresponding to the effects of one night's sleep
      deprivation. METHODS: In a randomized, double-blind fashion, 35 patients with
      mild to moderate essential hypertension received placebo run-in medication for 2
      weeks, followed by 4 weeks' moxonidine sustained release (1.5 mg o.d.) or
      placebo. On the first day and 1 and 4 weeks following the start of treatment,
      blood pressure was measured and CNS effects were assessed using SPV, visual
      analogue scales and EEG. RESULTS: On day 1 there was a significant, but not
      clinically relevant, reduction in the time-corrected area under the effect curve
      (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38
      degrees s-1; 95% confidence interval (CI) 23, 52]. This difference was no longer
      significant after one (9 degrees s-1; 95% CI -17, 35) and 4 weeks (6.9 degrees s
      1; 95% CI -16, 30). Visual analogue scales for alertness showed similar results.
      A decrease in EEG alpha- and beta-power and an increase in delta-power were only
      found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood
      pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day
      1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg
      after 1 and 4 weeks' moxonidine treatment. CONCLUSIONS: Four weeks' treatment
      with an experimental SR formulation resulted in tolerance to CNS effects
      (equivalence to placebo) while blood pressure-lowering effects remained adequate.
      The tolerance to CNS effects was already observed after 1 week of treatment.

PMID- 12814445
TI  - C-peptide has no effect on forearm blood flow during local hyperinsulinaemia in
      healthy humans.
AB  - BACKGROUND: C-peptide increases forearm blood flow (FBF) in patients with Type 1
      diabetes, probably by interaction with insulin, but not in healthy subjects. It
      is unclear if the vasodilating effect is sealed at normal fasting insulin
      concentrations. METHODS: The effects of C-peptide alone and during local
      hyperinsulinaemia were studied in healthy young men. Subjects received intra
      arterial insulin at 6 pmol min-1 (low dose) or placebo for 60 min with subsequent
      coinfusion of C-peptide at increasing doses of 2-60 pmol min-1 in a double-blind
      crossover study (n = 8). In control experiments insulin at 30 pmol min-1 (high
      dose) was coinfused with C-peptide (n = 3). FBF was measured by strain-gauge
      plethysmography. RESULTS: Placebo had no effect on FBF (mean percentage change
      from baseline at 50 min -3.1%, 95% confidence interval [CI]-14.9, + 8.7). Insulin
      infusion slightly enhanced FBF by + 10.2% (95% CI -6.8, + 27.2; low dose) and +
      17.6% (95% CI -38.8, + 74.0; high dose), respectively. The mean individual
      difference of the change in FBF between low-dose insulin and placebo was + 13.3%
      (95% CI -6.0, + 32.7; P = NS). Infusion of C-peptide increased local C-peptide
      concentrations from 1.8 +/- 0.1 ng ml-1 to 6.1 +/- 2.8 ng ml-1, but had no effect
      on FBF during placebo or hyperinsulinaemia (mean difference vs low dose insulin 
      16.0%, 95% CI -38.9, + 6.9). CONCLUSION: The vasodilating effect of C-peptide
      seen in Type 1 diabetes is not detectable during fasting or hyperinsulinaemia in
      the forearm vasculature of healthy subjects. This suggests saturation of its
      vasodilating potency at insulin concentrations within the normal or in the
      supraphysiological range.

PMID- 12814446
TI  - Chronotherapy of high-dose active vitamin D3 in haemodialysis patients with
      secondary hyperparathyroidsm: a repeated dosing study.
AB  - AIMS: Renal osteodystrophy is the major complication in patients with end-stage
      renal failure. Oral or intravenous vitamin D3 (D3) is given to these patients,
      but severe hypercalcaemia sometimes interrupts this therapy. This study was
      undertaken to determine whether the effectiveness and safety of D3 also depend on
      its dosing time during a repeated treatment. METHODS: A higher dose (3 micro g)
      was given orally to 13 haemodialysis patients at 08.00 h or 20.00 h for 12 months
      by a randomized, cross-over design. RESULTS: Three patients were withdrawn due to
      severe hypercalcaemia after switching from 08.00 h to 20.00 h dosings. The
      elevation in serum calcium concentration was significantly (P < 0.001) greater
      during the 08.00 h dosing in the remaining ten patients. Mean serum Ca
      concentration after the trial was 10.92 (95% confidence interval (CI) 10.79,
      11.06) and 9.55 mg dl-1 (95% CI 9.30, 9.71) by 08.00 h and 20.00 h dosing,
      respectively. On the other hand, the suppression of the elevated serum
      parathyroid hormone (PTH) and subsequent increment in bone density were
      significantly greater during the 08.00 h dosing. Mean PTH concentration after the
      trial was 414 (95% CI 360, 475) and 220 pg ml-1 (95% CI 202, 249) by 08.00 h and
      20.00 h dosing, respectively (P = 0.02). Mean increment of bone density after the
      trial was 22 (95% CI 8, 32) and 57 g cm-3 (95% CI 43, 83) by 08.00 h and 20.00 h
      dosing, respectively (P = 0.04). CONCLUSION: These results indicate that a higher
      dose of oral D3 is more effective and safe after dosing at evening in patients
      with renal osteodystrophy.

PMID- 12814447
TI  - The effect of motilin on the rectum in healthy volunteers.
AB  - AIMS: The role of motilin in the regulation of upper gastrointestinal (GI)
      motility is well defined. However, little is known about the effects on the
      distal GI tract. To investigate the effect of exogenous motilin on rectal
      function, barostat measurements in the rectum were performed and lower abdominal
      symptoms were scored. METHODS: Eight fasted, healthy volunteers were infused
      intravenously with synthetic motilin or placebo over 90 min in a double-blind,
      randomized, cross-over design. Rectum volume was measured with a barostat device
      during constant pressure and during isobaric distensions. Lower abdominal
      symptoms were scored by visual analogue scales. Plasma motilin concentrations
      were measured by radioimmunoassay. RESULTS: Baseline rectum volumes were similar
      between treatments: 185 +/- 62 mL (motilin) and 136 +/- 41 mL (placebo). During
      the constant pressure procedure, motilin increased rectum volume [area under the
      effect curve (AUEC)] by 6%[95% confidence interval (CI) -3, 16] of baseline,
      compared with placebo. During isobaric distensions motilin increased rectum
      volume (AUEC) by 43 mL (95% CI 0.4, 85; P < 0.05) and compliance by 10 mL mmHg-1
      (95% CI 0.3, 20; P < 0.05) relative to placebo. Motilin did not induce changes in
      the sensation of rectal feelings. CONCLUSION: Exogenous motilin increased rectal
      compliance in healthy volunteers, without affecting rectal sensations.

PMID- 12814448
TI  - Population pharmacokinetics of levosimendan in patients with congestive heart
      failure.
AB  - AIMS: The aim of this study was to characterize the population pharmacokinetics
      of levosimendan in patients with heart failure (NYHA grades III and IV) and its
      relationship to demographic factors, disease severity and concomitant use of
      digoxin and beta-blocking agents. METHODS: Data from two efficacy studies with
      levosimendan administered by intravenous infusion were combined (190 patients in
      total). The data were analysed using a nonlinear mixed-effects modelling approach
      as implemented in the NONMEM program. The model development was done in three
      sequential steps. First the best structural model was determined (e.g. a one-,
      two- or three-compartment pharmacokinetic model). This was followed by the
      identification and incorporation of important covariates into the model. Lastly
      the stochastic part of the model was refined. RESULTS: A two-compartment model
      best described levosimendan pharmacokinetics. Clearance and the central volume of
      distribution were found to increase linearly with bodyweight. No other
      covariates, including concomitant use of digoxin and beta-blocking agents,
      influenced the pharmacokinetics. In the final model, a 76-kg patient was
      estimated to have a clearance +/- s.e. of 13.3 +/- 0.4 l h-1 and a central volume
      of distribution of 16.8 +/- 0.79 l. The interindividual variability was estimated
      to be 39% and 60% for clearance and central volume of distribution, respectively.
      Weight changed clearance by 1.5% [95% confidence interval (CI) 0.9%, 2.1%] and
      the central volume of distribution by 0.9% (95% CI 0.5%, 1.3%) per kg.
      CONCLUSIONS: The population pharmacokinetics parameters of levosimendan in this
      patient group were comparable to those obtained by traditional methods in healthy
      volunteers and patients with mild heart failure. Bodyweight influenced the
      clearance and the central volume of distribution, which in practice is accounted
      for by weight adjusting doses. None of the other covariates, including digoxin
      and beta-blocking agents, significantly influenced the pharmacokinetics of
      levosimendan.

PMID- 12814449
TI  - Population pharmacokinetics of netilmicin in short-term prophylactic treatment.
AB  - AIMS: To characterize the population pharmacokinetics of netilmicin, an
      aminoglycoside antibiotic, in adult urology patients and to develop a covariate
      model for improved dose titration. METHODS: Data from 62 adult patients (55 male,
      seven female), undergoing urological surgery and treated with netilmicin for
      short-term prophylaxis, were evaluated retrospectively. The group had (median,
      range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm.
      No patient showed renal impairment before netilmicin treatment (serum creatinine
      </=1.9 mg dl-1). Netilmicin (100 mg) was administered as a maximum of four
      successive intravenous infusions of 30 min, at 8-h intervals. A total of five
      blood samples were collected from each patient. Prior to analysis, the dataset
      was divided into 'index' (n = 44) and 'validation' (n = 18) groups at random. The
      time courses of netilmicin concentrations from all subjects were analysed using a
      mixed effects, population, nonlinear modelling package (WinNonMix). For covariate
      model development, a stepwise procedure was used with backward elimination
      followed by forward inclusion based on age, sex, weight, height, creatinine
      clearance and type of surgery. The final covariate model parameters from the
      index group were used to simulate concentrations in the validation group and the
      bias and precision were compared with the observations. RESULTS: A bi
      compartmental open model with a proportional residual error best described the
      data. The population parameters for central and peripheral volumes of
      distribution were (typical population value [interindividual CV%]) Vc = 14.5 l
      [56%] and Vp = 10.2 l [not estimated], and the systemic and intercompartmental
      clearances were CL = 3.9 l h-1[42%] and CLQ = 10.1 l h-1[not estimated],
      respectively. The final population covariate relationships were based on sex
      (SEX) and creatinine clearance (CrCL): (Vc, l) = 18.9 - 5.9 x SEX [29%] and (CL,
      l h-1) = 0.06 x CrCL [33%]. Compared with the observations in the validation
      group, this model showed a bias (95% confidence interval) of -0.028 (-0.28, 0.25)
      and precision of 1.22 (0.78, 1.34). CONCLUSION: Bi-compartmental pharmacokinetic
      parameters of netilmicin have been estimated from clinical data in urological
      surgery patients using a population approach. A given single dose results in
      large variability in plasma concentrations and thus the population covariate
      final model can be used for direct estimation of initial dosing in patients.

PMID- 12814450
TI  - Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the
      Egyptian population.
AB  - AIMS: The goal of this study was to determine the frequencies of important
      allelic variants in the TPMT, NAT2, GST, SULT1A1 and MDR-1 genes in the Egyptian
      population and compare them with the frequencies in other ethnic populations.
      METHODS: Genotyping was carried out in a total of 200 unrelated Egyptian
      subjects. TPMT*2 was detected using an allele-specific polymerase chain reaction
      (PCR) assay. TPMT*3C and NAT2 variants (*5,*6 and *7) were detected using an
      allele-specific real-time PCR assay. Detection of GSTM1 and GSTT1 null alleles
      was performed simultaneously using a multiplex PCR assay. Finally, a PCR
      restriction fragment length polymorphism assay was applied for the determination
      of TPMT*3A (*3B), SULT1A1*2 and MDR-1 (3435T) variants. RESULTS: Genotyping of
      TPMT revealed frequencies of 0.003 and 0.013 for TPMT*3A and TPMT*3C,
      respectively. No TPMT*2 or *3B was detected in the analysed samples. The
      frequencies of specific NAT2 alleles were 0.215, 0.497, 0.260 and 0.028 for *4
      (wild-type), *5 (341C), *6 (590A) and *7 (857A), respectively. GSTM1 and GSTT1
      null alleles were detected in 55.5% and 29.5% of the subjects, respectively.
      SULT1A1*2 was detected at a frequency of 0.135. Finally, the frequencies of the
      wild-type allele (3435C) and the 3435T variant in the MDR-1 gene were found to be
      0.6 and 0.4, respectively. CONCLUSIONS: We found that Egyptians resemble other
      Caucasians with regard to allelic frequencies of the tested variants of NAT2, GST
      and MDR-1. By contrast, this Egyptian population more closely resemble Africans
      with respect to the TPMT*3C allele, and shows a distinctly different frequency
      with regard to the SULT1A1*2 variant. The predominance of the slow acetylator
      genotype in the present study (60.50%) could not confirm a previously reported
      higher frequency of the slow acetylator phenotype in Egyptians (92.00%),
      indicating the possibility of the presence of other mutations not detectable as
      T341C, G590A and G857A. The purpose of our future studies is to investigate for
      new polymorphisms, which could be relatively unique to the Egyptian population.

PMID- 12814451
TI  - A novel metabolic pathway of morphine: formation of morphine glucosides in cancer
      patients.
AB  - AIMS: To characterize directly the conjugated metabolites of morphine in urine
      samples of cancer patients. METHODS: Urine samples from the patients were treated
      by solid-phase extraction method and chromatographed using three high-performance
      liquid chromatography systems. Conjugated metabolites were directly detected with
      liquid chromatographic/ion trap mass spectrometric (LC/MSn) technique by selected
      ion monitoring, full scan MS/MS and MS3 modes. RESULTS: Six conjugated
      metabolites including two new metabolites M5 and M6 were found. Morphine-3
      glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) were identified by
      comparing their l.c. retention times and multistage mass spectra with those of
      the reference substances. Two novel metabolites, morphine-3-glucoside and
      morphine-6-glucoside, as well as normorphine glucuronides were identified by
      comparing their mass fragment patterns and l.c. retention times with those of M-3
      G and M-6-G. Hydrolysis of urine samples with beta-glucosidase and beta
      glucuronidase provided further evidence of the metabolites M5 and M6 as morphine
      glucosides. The excretion amounts of morphine conjugates in urines were in the
      order of morphine glucuronides, morphine glucosides and normorphine glucuronides.
      CONCLUSIONS: In the present study, the applications of l.c. separation and
      multistage mass spectra have permitted the direct identification of conjugated
      metabolites of morphine. To our knowledge, this is the first report about O
      linked glucosides of morphine at 3-aromatic and 6-aliphatic hydroxyl groups.

PMID- 12814452
TI  - Influence of age on the enantiomeric disposition of ibuprofen in healthy
      volunteers.
AB  - AIMS: To determine the influence of age on the enantioselective disposition of
      ibuprofen in humans. METHODS: Healthy young (n = 16; aged 20-36 years) and
      elderly (n = 16; aged 66-84 years) volunteers were given a 400-mg oral dose of
      racemic ibuprofen, and blood and urine samples were collected for 24 h post drug
      administration. Serum concentrations, total and free, and urinary excretion of
      both enantiomers of ibuprofen together with the urinary excretion of the
      stereoisomers of the two major metabolites of the drug, both free and conjugated,
      were determined by high-performance liquid chromatography. RESULTS: Ageing had
      little effect on the distribution and metabolism of R-ibuprofen, unbound
      clearance of the R-enantiomer via inversion being approximately two-fold that via
      noninversion mechanisms in both age groups. In contrast, the free fraction of S
      ibuprofen was significantly greater [33%; young 0.48 +/- 0.10%; elderly 0.64 +/-
      0.20%] mean difference -0.16; 95% confidence interval (CI) -0.05, -0.27; P <
      0.01; and the unbound clearance of the drug enantiomer was significantly lower
      (28%; young 15.9 +/- 2.2 l min-1; elderly 11.5 +/- 4.1 l min-1; mean difference
      4.4; 95% CI 2.12, 6.68; P < 0.001) in the elderly. The metabolite formation
      clearances of S-ibuprofen via glucuronidation, and oxidation at the 2- and 3-
      positions of the isobutyl side chain decreased by 24, 28 and 30%, respectively,
      in the elderly compared with the young, the differences between the two age
      groups being significant in each case (P < 0.05). CONCLUSIONS: Following
      administration of racemic ibuprofen age-associated stereoselective alterations in
      drug disposition have been observed, with the elderly having increased free
      concentrations and lower unbound clearance of the S-enantiomer in comparison with
      the young. In contrast, the handling of the R-enantiomer is essentially unaltered
      with age. The results of this study indicate that the elderly have an increased
      exposure to the active ibuprofen enantiomer and thus some caution may be required
      when using this drug in this age group.

PMID- 12814453
TI  - Evidence of an interaction between nifedipine and nafcillin in humans.
AB  - AIMS: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to
      induce the metabolism of cyclosporin and warfarin, which are known substrates of
      cytochrome P-450 (CYP). However, there has not been any report to date on its
      possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4.
      METHODS: Nine healthy normotensive subjects participated in this randomized
      placebo-controlled two-way crossover study examining the effects of 5 days'
      pretreatment of nafcillin 500 mg or placebo four times daily on the
      pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine
      concentrations were measured by gas chromatography-mass spectro. RESULTS: The
      area under the plasma nifedipine concentration-time curve (AUC0-alpha) in
      nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly
      decreased compared with subjects who received only nifedipine (216.4 +/- 93.2
      micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was
      significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5
      +/- 32.0 l h-1) (P < 0.002). CONCLUSIONS: The results show that nafcillin
      pretreatment markedly increased the clearance of nifedipine and suggest that
      nafcillin is a potent inducer of CYP enzyme.

PMID- 12814454
TI  - Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse
      effects.
AB  - AIMS: To investigate the relationship between the use of antidepressants with or
      without NSAIDs and the risk of gastrointestinal side-effects. METHODS: This was a
      population-based cohort study. Medication data of 180,000 patients from 16
      pharmacies in The Netherlands were studied. The subjects were a group of 15 445
      new users of antidepressants with or without NSAIDs. A review of patient profiles
      for cases of gastrointestinal adverse effects caused by first time use of
      antidepressants with or without NSAIDs was carried out. The number of first
      prescriptions for peptic ulcer drugs (Anatomical Therapeutic Chemical
      classification A02B) in the period from day 2 after starting antidepressants with
      or without NSAIDs until 10 days after the last dose was the main outcome measure.
      RESULTS: In the reference group of 619 new users of nonselective antidepressants
      (TCAs), the incidence of first prescriptions for peptic ulcer drugs was 0.051
      (95% confidence interval 0.021, 0.105). The use of SSRIs (n = 1181) caused a
      slightly higher incidence rate ratio (IRR) of 1.2 (0.5, 2.8). The combined use of
      SSRIs and NSAIDs (n = 86) increased the IRR to 12.4 (3.2, 48.0). In contrast, the
      combination of nonselective antidepressants and NSAIDs (n = 74) increased the IRR
      to 2.5 (0.3, 20.3). CONCLUSIONS: SSRIs increase the risk of gastrointestinal
      adverse effects in first time users as compared with nonselective
      antidepressants. The combined use of SSRIs and NSAIDs strongly increases the risk
      of gastrointestinal adverse effects and should be avoided. The combination of
      nonselective antidepressants and NSAIDs does not have this effect.

PMID- 12814455
TI  - Effects of licence change on prescribing and poisons enquiries for antipsychotic
      agents in England and Scotland.
AB  - AIMS: To examine the effect of licence change for thioridazine at the end of 2000
      on the prescription of antipsychotic drugs in England and Scotland, and
      investigate changes in poisons information inquiries and, for Edinburgh, poisons
      admissions. METHODS: Prescription data for antipsychotic drugs were obtained for
      England and Scotland and quarterly trends examined for 2000 and 2001. Accesses to
      the UK National Poisons Information Service website TOXBASE for antipsychotic
      products were examined for the same period. For Scotland telephone enquiry data,
      and admission data to the Edinburgh Poisons Unit were also evaluated. Trends in
      poisonings were compared with prescribing change. RESULTS: In England
      prescriptions for thioridazine fell rapidly in 2001 from approximately 35% of
      market share to less than 5%, and were replaced by risperidone, chlorpromazine
      and olanzapine. TOXBASE accesses fell from 39.3% of antipsychotics to 4.4%.
      Accesses for chlorpromazine, olanzapine and risperidone increased. In Scotland
      prescribing of thioridazine was similar to changes in England, but it was
      principally replaced by chlorpromazine. These changes were mirrored by TOXBASE
      accesses, telephone enquiries and in-patient admissions. The ratio of TOXBASE
      accesses for thioridazine to prescription numbers for the drug increased after
      the licence change. CONCLUSIONS: Licence change produced rapid change in
      prescribing behaviour within 3 months. Prescribing behaviour in England and
      Scotland was different. Changes in prescribing were mirrored by changes in
      accesses for poisons information in both England and Scotland, and in Edinburgh
      by hospital admissions. The increase in the ratio of TOXBASE accesses to
      prescriptions for thioridazine suggests doctors may have become more aware of its
      potential toxicity.

PMID- 12814456
TI  - Evidence for an age and gender bias in the secondary prevention of ischaemic
      heart disease in primary care.
AB  - AIMS: To determine if a gender or age bias exists in the prescription of
      important secondary preventive therapies for ischaemic heart disease in primary
      care. METHODS: We identified 15 590 patients with ischaemic heart disease on the
      basis that they received a prescription for nitrate therapy over a 1-year period
      (September 1999 to August 2000) from the Eastern Region of the General Medical
      Services scheme in Ireland (population of 334 031), which provides free health
      service to those eligible patients in primary care. Odds ratios (OR) for the
      prescription of aspirin, beta-blockers, statins, calcium channel antagonists and
      ACE inhibitors in women and in those aged> 65 years were determined. RESULTS:
      Female patients were less likely to receive a prescription for a beta-blocker [OR
      = 0.84, 95% confidence interval (CI) = 0.79, 0.89, P < 0.001], aspirin (OR =
      0.72, 95% CI = 0.67, 0.78, P < 0.001), and ACE inhibitors (OR = 0.83, 95% CI =
      0.78, 0.89, P < 0.001) compared with their male counterparts. However, women were
      more likely to receive anxiolytic benzodiazepines (OR = 1.71, 95% CI = 1.59,
      1.85, P < 0.001) compared with their male counterparts. Elderly patients (aged>
      65 years) were less likely to receive aspirin (OR = 0.92, 95% CI = 0.85, 0.99, P
      < 0.001), beta-blocker (OR = 0.66, 95% CI = 0.62, 0.71, P < 0.001) and a statin
      (OR = 0.5, 95% CI = 0.46, 0.53, P < 0.001). CONCLUSIONS: An age and gender bias
      exists in the prescription of important secondary preventive therapies in primary
      care that may lead to increased mortality from ischaemic heart disease in these
      groups.

PMID- 12814457
TI  - A proof of concept study to evaluate putative benefits of montelukast in moderate
      persistent asthmatics.
AB  - AIMS: Whether chronic dosing with montelukast confers benefit in patients with
      moderate to severe asthma remains to be fully established. A proof of concept
      study was performed evaluating putative benefits with montelukast in moderate
      persistent asthmatics who were taken off inhaled corticosteroids (ICS) and
      switched to salmeterol. The latter was done to dissociate the effects of
      montelukast from ICS. METHODS: Twenty moderate to severe persistent asthmatics
      completed a randomized double-blind crossover study. Subjects received
      montelukast 10 mg daily or placebo for 2 weeks each. This was preceded by a 2
      week run-in when ICS were discontinued and salmeterol started, and used on a
      regular basis throughout the study. Measurements were made after run-in and after
      both randomized treatments. RESULTS: There were no significant sequence effects
      for responses as to whether placebo or montelukast were given first or second.
      Methacholine PD20 values after run-in, first and second placebo were 63 micro g,
      60 micro g and 64 micro g, respectively (corresponding to 2, 4 and 6 weeks of ICS
      washout, respectively). Lung function deteriorated pre vs post run-in, which was
      significant (P < 0.05) for FEF25-75 % predicted. Montelukast conferred
      significant (P < 0.05) improvements as change from post run-in compared with
      placebo in methacholine PD20, FEV1 % predicted, FEF25-75 % predicted, diurnal
      peak expiratory flow, symptoms and salbutamol use. For the primary outcome of
      methacholine PD20, this amounted to a 1.6-fold difference (95% CI 1.1, 2.5).
      CONCLUSIONS: In moderate persistent asthmatics switched from taking ICS to
      salmeterol alone, adding montelukast conferred significant benefits on all
      parameters of asthma control. Further studies are indicated to evaluate whether
      montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor
      agonist combination inhalers upon clinically important outcomes.

PMID- 12814458
TI  - Comparison of the micro- and macro-vascular effects of glimepiride and gliclazide
      in metformin-treated patients with Type 2 diabetes: a double-blind, crossover
      study.
AB  - AIMS: To compare the metabolic and vascular effects of two sulphonylureas (SU),
      gliclazide (specific for the pancreatic [SUR1] receptor) and glimepiride (a
      nonspecific agent that also binds to vascular and cardiac [SUR2] receptors),
      during chronic administration in metformin-treated patients with Type 2 diabetes
      (T2DM). METHODS: A randomized, double-blind, crossover study of gliclazide 80 mg
      BID and glimepiride 2 mg OD, each for 4 weeks as add-on therapy to metformin,
      with a 4-week washout period. Patients attended four study mornings after first
      dose and 4 weeks' SU treatment for measurements of arterial distensibility (Ax),
      pressor responsiveness to i.v. angiotensin II (ANGII), and cutaneous
      microvascular vasodilator responses to iontophoresis of acetylcholine (ACh) and
      sodium nitroprusside (SNP). RESULTS: Glycaemic responses were similar (e.g. serum
      fructosamine was 315 vs 329 micro mol l-1 after 4 weeks), and there was no change
      in augmentation index during treatment with either SU (9.1 vs 9.8 mmHg after 4
      weeks [95% confidence interval -8.1, 10.5]). Similarly, there were no differences
      between treatments in pressor responsiveness (e.g. PD10[dose of agonist required
      to increase mean BP by 10 mmHg] for ANGII was 1.37 vs 1.68 ng kg-1 min-1[-4.3,
      6.9]) or cutaneous microvascular vasodilator responses (peak ACh response 68 +/-
      36 vs 63 +/- 34 perfusion units [-82.7, 79.1]). CONCLUSIONS: There is no evidence
      that SUR1-specific and nonspecific SUs have differential effects on arterial
      distensibility, endothelial function or vasodilator mechanisms in metformin
      treated patients with T2DM.

PMID- 12814459
TI  - Penetration of piperacillin and tazobactam into pneumonic human lung tissue
      measured by in vivo microdialysis.
AB  - OBJECTIVES: The pharmacokinetic profile of antibiotics at the site of anti
      infective action is one of the most important determinants of drug response,
      since it correlates with antimicrobial effect. Up to now, only limited
      information on the lung tissue pharmacokinetics of antibiotic agents has been
      available. The aim of this study was to measure, using a new microdialysis-based
      approach, antibiotic penetration into the extracellular space fluid of pneumonic
      human lung parenchyma. PATIENTS AND METHODS: The lung penetration of a
      combination of piperacillin and tazobactam, substances with low protein binding,
      was determined in five patients suffering from pneumonia and metapneumonic
      pleural empyema. The condition was treated by decortication after lateral
      thoracotomy. Intra-, or post-operatively, respectively, two microdialysis probes
      were inserted into pneumonic lung tissue, and into healthy skeletal muscle to
      obtain reference values. Serum and microdialysis samples were collected at 20-min
      intervals for at last 8 h following i.v. administration of a single dose of 4 g
      piperacillin and 500 mg tazobactam. RESULTS: The mean free interstitial
      concentration profiles of piperacillin in infected lung tissue and serum showed a
      maximal tissue concentration (Cmax) of 176.0 +/- 105.0 mg l-1 and 326.0 +/- 60.6
      mg l-1, respectively. The mean AUC (area under the curve) for infected lung
      tissue was 288.0 +/- 167.0 mg.h l-1 and for serum 470.0 +/- 142.0 mg.h l-1. There
      was a statistically significant difference between AUC (lung) and AUC (serum) (P
      = 0.018) as well as between AUC (lung) and AUC (muscle) (P = 0.043). The
      intrapulmonary concentrations of piperacillin and tazobactam exceeded the minimum
      inhibitory concentrations (MIC) for most relevant bacteria for 4-6 h. The
      procedure was well tolerated by all patients and no adverse events or
      microdialysis-associated side-effects were observed. CONCLUSION: This
      microdialysis technique enabled continuous tissue pharmacokinetic measurement of
      free, unbound anti-infective agents in the lung tissue of patients with
      pneumonia. The present data corroborate the use of piperacillin and tazobactam in
      the treatment of lung infections caused by extracellular bacteria and demonstrate
      the distribution of piperacillin and tazobactam in the interstitial space of
      pneumonic lung tissue.

PMID- 12814460
TI  - CYP3A5 phenotype-genotype correlations in a British population.
AB  - AIMS: To develop a polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP)-based assay to genotype for hepatic CYP3A5 expression and to
      use this assay to study a British population. METHODS: CYP3A5-specific primers
      were designed with one including a base-pair mismatch to create a RsaI site in
      samples positive for G6986 (CYP3A5*3 allele) [correction]. Following PCR and RsaI
      digestion, different band patterns on electrophoresis were predicted for
      individuals positive for CYP3A5 (CYP3A5*1 allele) compared with those who do not
      express the gene (CYP3A5*3 homozygotes). The assay was validated by DNA
      sequencing. DNA samples from a human liver bank consisting of 22 livers whose
      CYP3A5 expression had been determined by immunoblotting and a group of random
      individuals (n = 100) from the North-east of England were genotyped by the new
      assay. RESULTS: In the liver bank, five out of 22 samples expressed CYP3A5 at
      significant levels (>20 pmol mg-1 protein) and were found to have the genotype
      CYP3A5*1/CYP3A5*3 by the PCR-RFLP assay. All other liver DNA samples were
      CYP3A5*3 homozygotes. In the group of 100 random individuals, 13 had the genotype
      CYP3A5*1/CYP3A5*3 and all others were CYP3A5*3 homozygotes, predicting that 13%
      (95% confidence interval (CI) 6%, 20%) would show significant hepatic CYP3A5
      expression. The frequency for the CYP3A5*1 allele was 0.065 (95% CI 0.032,
      0.097). CONCLUSIONS: We have developed a simple assay for the detection of the
      CYP3A5*1/CYP3A5*3 alleles and shown that in a British population their frequency
      is similar to that reported previously. We have also shown a good correlation
      between hepatic CYP3A5 expression and genotype for a British Caucasian liver
      bank.

PMID- 12814461
TI  - Disposition of debrisoquine and nortriptyline in Korean subjects in relation to
      CYP2D6 genotypes, and comparison with Caucasians.
AB  - AIMS: To study the influence of the CYP2D6*10 allele on the disposition of
      debrisoquine and nortriptyline. METHODS: The pharmacokinetics of debrisoquine and
      nortriptyline and their main metabolites were determined in ten Koreans with the
      CYP2D6*1/*1 (n = 5) and CYP2D6*1/*10 (n = 5) genotypes after single oral doses of
      20 mg debrisoquine and 25 mg nortriptyline, respectively. The data were compared
      with previously published findings from 21 Caucasians with 0, one, two, three,
      four or 13 functional CYP2D6 genes. RESULTS: The AUC0-8 of 4-hydroxydebrisoquine
      was significantly lower in Koreans with CYP2D6*1/*10 genotype compared with
      CYP2D6*1/*1[95% confidence interval (CI) for the ratio between means 1.17, 1.85].
      No other genotype-related differences were found in the plasma kinetics of
      nortriptyline and debrisoquine, or their hydroxy metabolites. The
      AUCnortriptyline/AUC10-hydroxynortriptyline ratio did not differ between the
      *1/*1 and *1/*10 genotype groups (95% CI for the ratio of means 0.60, 1.26).
      Similarly, there was no difference between these genotypes with respect to the
      AUCdebrisoquine/AUC4-hydroxydebrisoquine ratio (95% CI for the ratio of mean
      values 0.38, 1.46). Both Korean genotype groups had similar AUCs and parent
      compound/metabolite AUC ratios of debrisoquine and nortriptyline to Caucasians
      with two functional CYP2D6 genes. CONCLUSIONS: Heterozygosity for CYP2D6*10
      decreases the CYP2D6-dependent elimination of nortriptyline and debrisoquine to
      only a limited degree. Further studies in subjects homozygous for CYP2D6*10 are
      required to elucidate fully the pharmacokinetic consequences of this CYP2D6
      genotype in Orientals.

PMID- 12814462
TI  - Polymorphic hydroxylation of perhexiline in vitro.
AB  - AIMS: The aims of this study were to examine the in vitro enzyme kinetics and CYP
      isoform selectivity of perhexiline monohydroxylation using human liver
      microsomes. METHODS: Conversion of rac-perhexiline to monohydroxyperhexiline by
      human liver microsomes was assessed using a high-performance liquid
      chromatography assay with precolumn derivatization to measure the formation rate
      of the product. Isoform selective inhibitors were used to define the CYP isoform
      profile of perhexiline monohydroxylation. RESULTS: The rate of perhexiline
      monohydroxylation with microsomes from 20 livers varied 50-fold. The activity in
      18 phenotypic perhexiline extensive metabolizer (PEM) livers varied about five
      fold. The apparent Km was 3.3 +/- 1.5 micro m, the Vmax was 9.1 +/- 3.1 pmol min
      1 mg-1 microsomal protein and the in vitro intrinsic clearance (Vmax/Km) was 2.9
      +/- 0.5 micro l min-1 mg-1 microsomal protein in the extensive metabolizer
      livers. The corresponding values in the poor metabolizer livers were: apparent Km
      124 +/- 141 micro m; Vmax 1.4 +/- 0.6 pmol min-1 mg-1 microsomal protein; and
      intrinsic clearance 0.026 micro l min-1 mg-1 microsomal protein. Quinidine almost
      completely inhibited perhexiline monohydroxylation activity, but inhibitors
      selective for other CYP isoforms had little effect. CONCLUSIONS: Perhexiline
      monohydroxylation is almost exclusively catalysed by CYP2D6 with activities being
      about 100-fold lower in CYP2D6 poor metabolizers than in extensive metabolizers.
      The in vitro data predict the in vivo saturable metabolism and pharmacogenetics
      of perhexiline.

PMID- 12814466
TI  - . . . Life lies waiting.

PMID- 12814463
TI  - The effects of histamine and leukotriene receptor antagonism on nasal mannitol
      challenge in allergic rhinitis.
AB  - AIMS: It is unclear as to which mediators are involved in mediating the response
      to nasal mannitol challenge, a novel osmotic stimulus. METHODS: A double-blind,
      randomized, placebo-controlled, crossover design was employed. Nine patients with
      allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg,
      montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal
      peak inspiratory flow recordings over 60 min. The change in peak nasal
      inspiratory flow was calculated as percentage change from baseline as the peak
      response and area under the time-response curve (AUC). RESULTS: Desloratadine and
      montelukast conferred a significant degree of protection compared to placebo for
      peak and AUC response, but there were no significant differences between the two
      drugs. For the peak response as percentage fall, the mean difference (95% CI) vs
      placebo was 27.7 (8.0, 47.4)% for desloratadine and 17.6 (1.9, 33.3)% for
      montelukast. CONCLUSIONS: Our results suggest that histamine and cysteinyl
      leukotrienes are involved in mediating the response to nasal mannitol in allergic
      rhinitis.

PMID- 12814467
TI  - Anemia after kidney transplantation--is the incidence increasing?

PMID- 12814468
TI  - Report card on living kidney donation.

PMID- 12814469
TI  - The report of a national conference on the wait list for kidney transplantation.
AB  - In March, 2002, over 100 members of the transplant community assembled in
      Philadelphia for a meeting designed to address problems associated with the
      growing number of patients seeking kidney transplantation and added to the
      waiting list each year. The meeting included representatives of nine US
      organizations with interests in these issues. Participants divided into work
      groups addressing access to the waiting list, assigning priority on the list,
      list management, and identifying appropriate candidates for expanded criteria
      donor kidneys. Each work group outlined problems and potential remedies within
      each area. This report summarized the issues and recommendations regarding the
      waiting list for kidney transplantation addressed in the Philadelphia meeting.

PMID- 12814470
TI  - Smallpox and live-virus vaccination in transplant recipients.
AB  - Recent bioterrorism raises the specter of reemergence of smallpox as a clinical
      entity. The mortality of variola major infection ('typical smallpox') was
      approximately 30% in past outbreaks. Programs for smallpox immunization for
      healthcare workers have been proposed. Atypical forms of smallpox presenting with
      flat or hemorrhagic skin lesions are most common in individuals with immune
      deficits with historic mortality approaching 100%. Smallpox vaccination, even
      after exposure, is highly effective. Smallpox vaccine contains a highly
      immunogenic live virus, vaccinia. Few data exist for the impact of variola or
      safety of vaccinia in immunocompromised hosts. Both disseminated infection by
      vaccinia and person-to-person spread after vaccination are uncommon. When it
      occurs, secondary vaccinia has usually affected individuals with pre-existing
      skin conditions (atopic dermatitis or eczema) or with other underlying immune
      deficits. Historically, disseminated vaccinia infection was uncommon but often
      fatal even in the absence of the most severe form of disease, "progressive
      vaccinia". Some responded to vaccinia immune globulin. Smallpox exposure would be
      likely to cause significant mortality among immunocompromised hosts. In the
      absence of documented smallpox exposures, immunocompromised hosts should not be
      vaccinated against smallpox. Planning for bioterrorist events must include
      consideration of uniquely susceptible hosts.

PMID- 12814471
TI  - Clinical trials of transplant tolerance: slow but steady progress.
AB  - The search for tolerance therapies that would thwart the alloimmune response
      following organ transplantation while preserving a patient's protective immune
      response has been a formidable goal for clinical immunologists. Over the past few
      decades, a more detailed understanding of the molecular events associated with T
      cell recognition and activation has demonstrated the feasibility of various
      tolerance approaches, such as costimulation blockade, in numerous animal models
      of both autoimmunity and transplantation. Yet, only a few promising new therapies
      have reached the early stages of human clinical development. In contrast, the use
      of T-cell depleting induction therapy has become widespread, and new trials have
      been designed with immunosuppressive drug withdrawal in mind. Furthermore,
      nonmyeloablative mixed chimeric approaches have allowed complete
      immunosuppressive withdrawal in some limited cases. In the course of these
      investigations, however, what has become increasingly clear is that the
      distinctions between immunosuppression and tolerance have been blurred as the
      success and durability of the therapies rely as much on the state of the organ
      and organism as they do the mechanism of action of the drug. In this review, we
      provide a summary of the progress and lessons in promoting clinical transplant
      tolerance and an overview of promising agents.

PMID- 12814472
TI  - Lack of role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells
      via BMT and anti-CD40L.
AB  - Anti-CD40L mAb plus bone marrow transplantation (BMT) and recipient CD8 T-cell
      depletion permits long-term mixed hematopoietic chimerism and systemic donor
      specific tolerance to be achieved across full MHC barriers. Initial tolerance is
      characterized by peripheral deletion of donor-reactive CD4 cells. In regimens
      using costimulatory blockade without BMT to achieve allograft survival,
      cyclosporine inhibited graft survival, suggesting that the combination may not be
      clinically applicable. We assessed the role of cyclosporine-sensitive mechanisms
      and the mechanisms of T-cell apoptosis involved in the induction of early
      peripheral CD4+ T-cell tolerance by BMT with anti-CD40L. Neither a short course
      of cyclosporine (14 days) nor the absence of FAS-mediated activation-induced cell
      death (AICD) blocked the induction or maintenance of donor-specific tolerance. IL
      2 production was not associated with tolerance induction, consistent with the
      lack of a role for Fas-mediated AICD. Mice in which passive T-cell death was
      impaired because of constitutive expression of a Bcl-xL transgene did not develop
      tolerance with this protocol. These data confirm that deletion of donor-reactive
      T cells is critical for the induction of mixed chimerism and tolerance. However,
      the mechanisms involved may differ from those involved in costimulatory blockade
      regimens that do not include BMT.

PMID- 12814473
TI  - Treatment by mycophenolate mofetil of advanced graft vascular disease in non
      human primate recipients of orthotopic aortic allografts.
AB  - Failure to control chronic graft dysfunction [e.g. graft vascular disease (GVD)]
      is the primary cause of immunologic graft failure. This is the first study of
      mycophenolate mofetil (MMF) for the treatment of GVD in non-human primate
      recipients of aortic allografts. Abdominal aortic allografts were exchanged
      between mixed leukocyte reaction (MLR) -mismatched, blood-group-compatible
      cynomolgus monkeys. Six control recipients were untreated. Individualized
      treatment with frequent dose adjustments of MMF insured that treatment was close
      to the maximum tolerated dose (mean 99.2 mg/kg/day). Immune-mediated injury
      proceeded unhindered until day 45, after which MMF treatment began. Changes in
      intimal volume (IV) were quantified by intravascular ultrasound (IVUS) and
      compared to histology on day 105. Serial IVUS measurements of IV (mm(3)) in
      controls showed progressive GVD. In four out of six animals, MMF was well
      tolerated, thus enabling optimum treatment; in all these animals, IV was
      significantly less than in the control animals (p = 0.02). In the two remaining
      animals, high doses were not tolerated; at day 105, there was no significant
      difference in IV between them and the controls. We found a significant
      correlation between the mean MMF tolerated dose and the inhibition of progression
      of IV (r = -0.88, p = 0.015). When high MMF doses were tolerated, MMF slowed
      progression of GVD.

PMID- 12814474
TI  - Morbidity and mortality after living kidney donation, 1999-2001: survey of United
      States transplant centers.
AB  - There have been two recent trends in living kidney donation: increased acceptance
      of living donors and increased acceptance of laparoscopic nephrectomy (LN). We
      surveyed 234 UNOS-listed kidney transplant programs to determine current living
      donor morbidity and mortality for open nephrectomy, hand-assisted LN, and non
      hand-assisted LN. Of the 234 centers, 171 (73%) responded. Between 1/1/1999 and
      7/1/2001, these centers carried out 10 828 living donor nephrectomies: 52.3%
      open, 20.7% hand-assisted LN, and 27% non-hand-assisted LN. Two donors (0.02%)
      died from surgical complications and one is in a persistent vegetative state (all
      after LN). Reoperation was necessary in 22 (0.4%) open, 23 (1.0%) hand-assisted
      LN, and 21 (0.9%) non-hand-assisted LN cases (p = 0.001). Complications not
      requiring reoperation were reported for 19 (0.3%) open, 22 (1.0%) hand-assisted
      LN, and 24 (0.8%) non-hand-assisted LN cases (p = 0.02). Readmission rate was
      higher for LN (1.6%) vs. open (0.6%) donors (p < 0.001), almost entirely as a
      result of an increase in gastrointestinal complications in LN donors. Morbidity
      and mortality for living donor nephrectomy at transplant centers in the United
      States remain low. We provide current data from which comprehensive informed
      consent can be obtained from donors.

PMID- 12814475
TI  - Prevalence and management of anemia in renal transplant recipients: a European
      survey.
AB  - The TRansplant European Survey on Anemia Management (TRESAM) documented the
      prevalence and management of anemia in kidney transplant recipients. Data from 72
      transplant centers in 16 countries were screened, involving 4263 patients who had
      received transplants 6 months, 1, 3 or 5 years earlier. The mean age of
      transplant recipients was 45.5 years at transplantation. The most common etiology
      was chronic glomerulonephritis. The most common comorbidities were coronary
      artery disease, hepatitis B/C, and type 2 diabetes. The mean hemoglobin levels
      before transplantation were significantly higher in the more recently
      transplanted recipients. At enrollment, 38.6% of patients were found to be
      anemic. Of the 8.5% of patients who were considered severely anemic, only 17.8%
      were treated with epoetin. There was a strong association between hemoglobin and
      graft function; of the 904 patients with serum creatinine > 2 mg/dL, 60.1% were
      anemic, vs. 29.0% of those with serum creatinine <or= 2 mg/dL (p < 0.01). Therapy
      with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor
      antagonists, mycophenolate mofetil (MMF) or azathioprine was also associated with
      a higher likelihood of anemia. The prevalence of anemia in the transplant
      recipients was remarkably high and appeared to be associated with impaired renal
      function and with ACE inhibitors and angiotensin II receptor antagonist use.
      Further studies should be carried out to interpret whether appropriate management
      of anemia after kidney transplantation may improve long-term outcome.

PMID- 12814476
TI  - Pharmacodynamics of single doses of the novel immunosuppressant FTY720 in stable
      renal transplant patients.
AB  - FTY720, a new and potent immunosuppressant, causes in animal models a rapid,
      reversible reduction of all subsets of peripheral blood lymphocytes, inducing
      their migration to secondary lymphoid organs. In this human phase I trial, the
      pharmacodynamics of single oral doses of FTY720 were evaluated. A randomized,
      double-blind, placebo-controlled, time-lagged study of six different single
      ascending oral doses of FTY720 ranging from 0.25 to 3.5 mg was conducted in
      stable renal transplant patients receiving a cyclosporine-based regimen. Absolute
      and subset lymphocyte counts, as well as absolute differential leukocyte counts,
      were determined by differential blood counts and flow cytometry at screening and
      multiple intervals thereafter. A pharmacodynamic model was established. Twenty
      four single doses of FTY720 that were administered caused a transient, reversible
      pan-lymphopenia within 4 h. Lymphocyte subgroup analysis revealed that almost all
      subsets declined, with CD4- and CD45RA-positive cells being affected the most.
      Natural killer cells, granulocytes and monocytes were not influenced by FTY720.
      The lymphocyte count returned to baseline within 72 h in all dosing cohorts
      except the highest. Pharmacokinetik/pharmacodynamic modelling revealed a
      nonlinear dose effect and resulted in a good fit with observed values. These data
      show that FTY720 is highly effective in humans, with single oral doses of FTY720
      ranging from 0.25 to 3.5 mg causing a reversible selective panlymphopenia.

PMID- 12814477
TI  - Prospective, randomized, multi-center trial of antibody induction therapy in
      simultaneous pancreas-kidney transplantation.
AB  - A randomized, multicenter, prospective study was conducted at 18 pancreas
      transplant centers in the United States to determine the role of induction
      therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74
      recipients were enrolled: 87 recipients each in the induction and noninduction
      treatment arms. Maintenance immunosuppression consisted of tacrolimus,
      mycophenolate mofetil, and corticosteroids. There were no statistically
      significant differences between treatment groups for patient, kidney, and
      pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated
      biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the
      induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28),
      respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute
      kidney allograft rejection in the induction and noninduction treatment arms was
      13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft
      rejection occurred later post-transplant and appeared to be less severe among
      recipients that received induction therapy. The highest rate of Cytomegalovirus
      (CMV) viremia/syndrome was observed in the subgroup of recipients who received T
      cell depleting antibody induction and received organs from CMV serologically
      positive donors. Decisions regarding the routine use of induction therapy in SPK
      transplantation must take into consideration its differential effects on risk of
      rejection and infection.

PMID- 12814478
TI  - Benefit of child-to-parent kidney donation.
AB  - Use of child-to-parent (CTP) kidney donation may be limited because of ethical
      concerns as well as doubts about its effectiveness. We used the United Network
      for Organ Sharing database to examine the effectiveness of CTP kidney donation
      compared with other types of living-related (LD) kidney donation and to cadaveric
      kidney donation. Data from 56 873 kidney transplants performed between 1988 and
      1998 showed significantly greater transplant and patient survival for CTP kidney
      transplants compared with cadaveric kidney transplants. The average gain in
      kidney transplant half-life is 3.6 years for a CTP compared with a cadaveric
      kidney transplant, and it is estimated that this gain for the recipient far
      outweighs the 1 in 3000 risk of death to the donor associated with kidney
      donation. We conclude that CTP kidney donation should not be discouraged, and
      represents a useful source of transplantable kidneys.

PMID- 12814479
TI  - Post transplant erythrocytosis in hypercalcemic renal transplant recipients.
AB  - In vitro data suggest that calcium plays an important role in normal and
      disordered erythropoiesis. The purpose of this study is to determine whether
      there is an association between serum calcium, various hormone levels, and the
      development of post transplant erythrocytosis (PTE). Data were collected on 283
      patients who underwent renal transplantation between 1994 and 1998. The
      relationship between serum calcium and PTE development was tested using the chi
      square test. Univariate and multivariable adjusted models were employed to
      determine predictors of maximum hematocrit. Selected patients underwent
      measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and
      erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant
      erythrocytosis was more common in patients with hypercalcemia compared with
      patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable
      analyses, serum calcium was a strong independent predictor of maximum hematocrit
      post transplant, even after adjustment for renal function. A serum calcium of
      >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE.
      There were no differences in hormone levels between subjects with hypercalcemia
      and PTE, subjects with PTE alone, and subjects with hypercalcemia alone.
      Hypercalcemia is associated with the development of PTE in renal transplant
      recipients.

PMID- 12814480
TI  - Enzyme linked immunosorbent spot (ELISPOT) assay for interferon-gamma
      independently predicts renal function in kidney transplant recipients.
AB  - Post-transplant monitoring of cellular immunity might be useful in predicting
      long-term outcomes of kidney transplant recipients. We used an enzyme linked
      immunoabsorbent spot (ELISPOT) assay to serially measure the frequency of
      peripheral blood lymphocytes producing interferon-gamma in response to stimulator
      cells from donors or third parties in 55 primary kidney transplant recipients.
      Mean frequencies measured during the first 6 months after transplantation
      correlated significantly with the serum creatinine concentration at both 6 and 12
      months following transplantation. The mean frequencies were higher in patients
      with acute rejection than in those without acute rejection. Multiple regression
      analyses indicated that the correlations between the early ELISPOT measurements
      of interferon-gamma and serum creatinine were independent of acute rejection,
      delayed graft function, or the presence of panel reactive antibodies before
      transplantation. Patients with low mean frequencies of interferon-producing cells
      in the early post-transplant period were generally free from acute rejection and
      exhibited excellent renal function at 6 and 12 months post-transplant. In
      conclusion, using the ELISPOT assay, we show an independent correlation between
      early cellular alloreactivity and long-term renal function. Increased levels of
      early alloreactivity measured with this assay may serve as a surrogate for
      chronic allograft dysfunction.

PMID- 12814481
TI  - Risk factors for and clinical course of non-anastomotic biliary strictures after
      liver transplantation.
AB  - Non-anastomotic biliary stricture (NAS) formation is a major complication of
      liver transplantation. We prospectively determined the time to development of
      responsiveness to treatment, and clinical outcomes following NAS formation. In
      addition, an extensive analysis of the association of recipient, donor, and
      clinical variables with NAS formation was performed. A total of 749 consecutive
      patients was studied in a prospective, protocol-based fashion. Seventy-two
      patients (9.6%) developed NAS at a mean of 23.6 +/- 34.2 weeks post
      transplantation. Non-anastomotic biliary stricture formation resolved in only 6%
      of affected patients. Although patient survival was not affected,
      retransplantation and graft loss rates were significantly greater in recipients
      who developed NAS. In contrast to previous reports, a pretransplant diagnosis of
      HCV was associated with a low frequency of NAS formation. The incidence of NAS
      was independently associated with pretransplant diagnoses of PSC and autoimmune
      hepatitis. Hepatic artery thrombosis, and prolonged warm and cold ischemia times
      were also independent risk factors for NAS formation. We conclude that NAS
      developed in approximately 10% of primary liver transplant recipients. A
      pretransplant diagnosis of autoimmune hepatitis has been identified as a novel
      independent risk factor for NAS formation. Development of NAS significantly
      attenuates graft but not patient survival.

PMID- 12814482
TI  - Tracheostomy following lung transplantation predictors and outcomes.
AB  - The effect of tracheostomy on patients receiving lung transplantation is unknown.
      We reviewed our experience by performing a retrospective analysis on all lung
      transplant recipients at our institution. Patients were assigned to each study
      group based on whether or not they received a tracheostomy in the acute
      postoperative period. One hundred and fourteen lung transplants were performed,
      and 16 of those patients received a tracheostomy. In the tracheostomy group, more
      patients had undergone bilateral-lung transplantation (81% vs. 34%, p = 0.001),
      more required cardiopulmonary bypass (75% vs. 38%, p = 0.005), more acquired
      postoperative pneumonia (88% vs. 30%, p < 0.001), had greater reperfusion injury
      at 48 h (PaO2/FiO2 of 233 vs. 345, p = 0.047), had longer initial periods on the
      ventilator (21 +/- 7 vs. 2 +/- 0.5 days, p < 0.001), more required re-intubation
      (56% vs. 18%, p = 0.001), spent longer times in the intensive care unit (30 +/- 7
      vs. 5.5 +/- 0.9 days, p < 0.001), and had longer lengths of stay (67 +/- 10 vs.
      22 +/- 2 days, p < 0.001). Despite these differences between the two groups, a
      significant difference in survival at 180 days (75 vs. 81%) did not exist (p =
      0.89). Although tracheostomy is more likely in sicker patients, it is not
      associated with poor long-term outcomes.

PMID- 12814483
TI  - Conventional immunosuppression is compatible with costimulation blockade-based,
      mixed chimerism tolerance induction.
AB  - T-cell costimulatory blockade has emerged as an effective strategy to prevent
      allograft rejection in experimental models. We and others have reported that the
      beneficial effects of costimulation blockade can be negated when combined with
      certain immunosuppressants. The current study evaluates the compatibility of
      various immunosuppressive agents in a costimulation blockade-based, mixed
      chimerism tolerance protocol. The addition of conventional agents, including
      calcineurin inhibitors, did not interfere with tolerance induction. All mice
      developed multilineage macrochimerism and accepted donor allografts. Analysis of
      specific T-cell receptor utilization demonstrated selective deletion of donor
      reactive T cells. Challenge with donor and third-party allografts confirmed donor
      specific tolerance. Clinical introduction of costimulation blockade-based
      strategies will likely incorporate currently approved immunosuppressive agents.
      While it has been reported that certain conventional agents are detrimental to
      costimulation blockade-based strategies, our results suggest that these agents
      could safely be combined in clinical trials when used as part of a
      nonmyelosuppressive, mixed chimerism-based tolerance strategy.

PMID- 12814484
TI  - Low prevalence of colonization with vancomycin-resistant Enterococcus in patients
      awaiting liver transplantation.
AB  - The orthotopic liver transplant (OLT) population has been particularly affected
      by the increase in vancomycin-resistant enterococcus (VRE) infections in recent
      years. Pre-transplant colonization prevalence, the role of spontaneous bacterial
      peritonitis (SBP) antimicrobial prophylaxis as a risk factor, and the risk of
      post-OLT infection in colonized patients are all unknowns. We prospectively
      evaluated OLT candidates at our center with the aim of answering these questions.
      Vancomycin-resistant enterococcus colonization status was determined by rectal
      culture. Data collected included illness severity, antibiotic use (including SBP
      prophylaxis), waiting time, previous hospitalizations, and invasive procedures.
      Eighty-eight patients (31 female, 57 male, median age 52 years) were enrolled.
      The most common diagnoses were hepatitis C (49%), primary sclerosing cholangitis
      (13.6%), and alcoholic liver disease. Median MELD score was 11.5 (range 7-24),
      and median waiting time was 551 days (range 1-2224). Vancomycin-resistant
      enterococcus risk factors were common in our patients: recent hospitalization in
      16%, recent antibiotic exposure in 39%, and renal insufficiency in 7%. Seventeen
      percent were receiving SBP prophylaxis. Despite the presence of established risk
      factors, VRE colonization prevalence was 3.4%. Preliminary limited data showed
      poor correlation between screening rectal cultures and operative/peri-operative
      cultures. Vancomycin-resistant enterococcus colonization prevalence in an OLT
      candidate population with mid-level MELD scores was low, and SBP prophylaxis was
      not a significant risk factor.

PMID- 12814485
TI  - Interaction between sibutramine and cyclosporine.

PMID- 12814488
TI  - Population drinking and alcohol harm: what these Canadian analyses tell us.

PMID- 12814489
TI  - Addiction, neuroscience and ethics.

PMID- 12814490
TI  - The 'brain disease' idea, drug policy and research ethics.

PMID- 12814491
TI  - Are over-simplified views of addiction neuroscience providing too simplified
      ethical considerations?

PMID- 12814492
TI  - Addiction, ethics and scientific freedom.

PMID- 12814493
TI  - Conversation with Conan Kornetsky.

PMID- 12814494
TI  - Alcohol consumption and fatal accidents in Canada, 1950-98.
AB  - AIMS: To evaluate the effects of changes in aggregate alcohol consumption on
      overall fatal accidents, motor vehicle accidents, fatal falling accidents and
      drowning accidents in Canadian provinces after 1950. DESIGN: Time-series analysis
      of annual mortality rates (15-69 years) in relation to per capita alcohol
      consumption, utilising the Box-Jenkins technique. All series were differenced to
      remove long-term trends. MEASUREMENTS: Gender-specific and age-adjusted mortality
      rates for the age group 15-69 years were calculated on the basis of mortality
      data for 5-year age groups, using a standard population. Data on per capita
      alcohol consumption was converted to consumption per inhabitant 15 years and
      older. In the analysis of motor vehicle accidents, the number of motor vehicles
      was used as a control variable. FINDINGS: Statistically significant associations
      between alcohol consumption and overall fatal accident rates were uncovered in
      all provinces for males, and in all provinces except Ontario for females. For
      Canada at large, an increase in per capita alcohol consumption of 1 litre was
      accompanied by an increase in accident mortality of 5.9 among males and 1.9 among
      females per 100,000 inhabitants. Among males there was a significant association
      with alcohol for both falling accidents, motor vehicle accident and other
      accidents, but the association was insignificant for drowning accidents. Among
      females, the association with falling accidents and other accidents was
      significant. CONCLUSION: Changes in alcohol consumption have had substantial
      effects on most of the main types of fatal accidents in Canada during the second
      half of the 20th century. The size of the association is comparable to the one
      previously reported from Northern Europe.

PMID- 12814495
TI  - Physicians' enquiries into their patients' alcohol use: public views and recalled
      experiences.
AB  - AIMS: To examine public opinion and experiences of family physician involvement
      in alcohol use issues and to identify patient characteristics associated with
      these opinions and experiences. DESIGN: A secondary analysis of population survey
      data from the 1993 Ontario Alcohol and Other Drug Opinion Survey (OADOS), a
      random household telephone survey of adults in Ontario, Canada. Opinion and
      experiences regarding alcohol use were examined by drinking status. PARTICIPANTS:
      All survey respondents (n = 941; 65% response rate). Population expansion weights
      were applied to ensure the sample's representativeness of the adult population of
      Ontario. MEASUREMENTS: Measures assessed the prevalence of opinions and
      experiences of family physicians: (1) asking patients about their drinking; (2)
      advising regular drinkers to cut down/quit; and (3) helping patients with alcohol
      problems. Self-reported past-year alcohol consumption and related problems were
      used to construct a categorical variable describing current drinking status.
      FINDINGS: Public opinion supported routine inquiries into patients' drinking
      habits and advising regular drinkers to cut down. However, the experience of
      being asked by a physician about drinking, being advised to cut down or being
      helped with alcohol problems was uncommon. Respondents' drinking status was
      associated with experiences of being asked about drinking and being advised to
      cut down. CONCLUSIONS: Physician training should inform physicians that public
      opinion supports inquiries about drinking and advisement to reduce consumption,
      as it does not appear that family doctors are meeting these expectations of
      patients.

PMID- 12814496
TI  - How important is treatment? One-year outcomes of treated and untreated alcohol
      dependent individuals.
AB  - AIMS: To compare representative treatment and untreated samples of alcohol
      dependent individuals in rates of abstinence and non-problematic use at 1-year
      follow-up. PARTICIPANTS AND DESIGN: A total of 482 alcohol-dependent adults in a
      northern California county identified through a probability survey of problem
      drinkers in the general population (n = 111) or a survey of consecutive
      admissions to public and private substance abuse programs (n = 371) were
      interviewed in person at baseline and by telephone at 1 year. MEASUREMENTS:
      Logistic regression models were used to predict 30-day abstinence and 12-month
      non-problematic alcohol use. RESULTS: At follow-up, alcohol-dependent individuals
      in the treatment sample had higher abstinence rates and non-problematic use
      outcomes than those in the untreated general population sample. In logistic
      regression models of the merged samples, being in the treatment sample was
      related strongly and positively to abstinence and non-problematic use. Having
      more drug users and heavy drinkers in one's social network, higher psychiatric
      comorbidity, and more social consequences were inversely related to abstinence
      and non-problematic use in the treatment sample. The number of drug users and
      heavy drinkers in one's social network was also inversely related to abstinence
      in both the treatment and untreated general population samples. Results
      predicting non-problematic use were similar. CONCLUSIONS: These results are
      consistent with other studies that examine treatment effectiveness in the absence
      of a controlled trial. Although natural recovery also occurs, alcohol-dependent
      individuals benefit from treatment. Co-occurring psychiatric problems continue to
      be major barriers to treatment effectiveness. An emphasis on changing social
      networks to be conducive to recovery could heighten both clinical effectiveness
      and prevention efforts within communities.

PMID- 12814497
TI  - Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers.
AB  - AIM: This study examined the effect of nicotine deprivation on alcohol and
      smoking urges in a sample of alcohol-dependent smokers in early recovery. DESIGN:
      Using a within-subjects design, participants underwent two cue-reactivity
      laboratory sessions in which they rated their urges for alcohol and cigarettes
      during the following three trials: baseline, neutral cue and mood induction
      combined with alcohol beverage cue exposure. One session was completed after 34
      hours of nicotine deprivation and another in a non-deprived state. PARTICIPANTS:
      Forty alcohol-dependent heavy smokers recruited from a substance abuse day
      treatment program. MEASUREMENTS: Self-reported urge to drink, urge to smoke and
      salivation. FINDINGS: Results showed that during the non-deprived session,
      alcohol cue presentations were associated with significant increases in urges to
      drink and urges to smoke. Acute nicotine deprivation led to increased smoking
      urges, but was not associated with increased urges to drink alcohol. CONCLUSIONS:
      Findings suggest that the acute effects of smoking cessation are unlikely to
      increase risk of relapse to alcohol in alcoholic patients who are undergoing
      treatment.

PMID- 12814498
TI  - The association of current smoking behavior with the smoking behavior of parents,
      siblings, friends and spouses.
AB  - AIMS: To examine the association of current smoking behavior of adolescents and
      young adults with the smoking behavior of their parents, siblings, friends and
      spouses. DESIGN: Using survey data from a large twin-family sample, the
      association between the smoking behavior of participants and that of their family
      members, friends and spouses was investigated by calculating the relative risk.
      To disentangle sex and age differences, calculations were carried out separately
      for males and females and for three different age groups: 12-15, 16-20 and 21-40
      years old. FINDINGS: The smoking behavior of the participants was significantly
      influenced by the smoking behavior of parents, siblings and friends, but all
      relative risks decreased with age. No differences in relative risk were found
      between having older or younger smoking siblings. Within each age group, the
      relative risk to smoke when having a smoking friend was comparable to the
      relative risk to smoke when having a smoking same-age and same-sex sibling. For
      the older participants, the relative risk to smoke was higher for monozygotic
      (MZ) twins with a smoking co-twin than for dizygotic (DZ) twins with a smoking co
      twin. Most findings were sex-dependent: same-sex smoking family members
      influenced smoking behavior more than opposite-sex family members. The
      significant association of the smoking behavior of spouses decreased with age,
      which suggests that assortment for smoking is based on similarity at the time
      dating began. CONCLUSIONS: The results highlight the importance of both social
      and genetic influences on smoking behavior, with genetic influences increasing
      with the age of the participant.

PMID- 12814499
TI  - Tobacco use by university students, Lebanon, 2001.
AB  - AIMS: The objective was to determine the prevalence of smoking [cigarettes and/or
      narghile (i.e. water-pipe)] among university students and to examine multiple
      correlates. DESIGN: Cross-sectional. SETTING: Beirut, Lebanon. PARTICIPANTS: A
      proportionate random sample of 1964 students from public and private universities
      in Beirut, Lebanon. MEASUREMENTS: Participants completed a self-administered
      anonymous questionnaire that included demographic and scholastic items and health
      behavioral aspects, including smoking, alcohol, physical activity, weight control
      measures and seat belt use. FINDINGS: The overall prevalence of smoking was 40%
      (21.1%, 7.6% and 11.3% of the students were smoking only narghile, only
      cigarettes and both cigarettes and narghile, respectively). Regression analyses
      showed that males, those of non-Lebanese origin, pursuing undergraduate degrees,
      performing risky weight control measures and drinking excessive amounts of
      alcohol had increased odds of smoking cigarettes. Also, age, high level of
      paternal education and field of study were significant predictors. Narghile
      smoking was significantly higher among males who drank excessive alcohol.
      CONCLUSIONS: The authors advocate a collaborative effort to alleviate the
      consequences of smoking among university students.

PMID- 12814500
TI  - Impact of messages on concomitant use of nicotine replacement therapy and
      cigarettes: a randomized trial on the Internet.
AB  - AIMS: To assess the impact of messages recommending the concomitant use of
      nicotine replacement therapy (NRT) and cigarettes on smokers' intention to quit
      smoking. DESIGN: Randomized trial. SETTING: Internet. PARTICIPANTS: A total of
      2027 people who answered an e-mail sent to 9074 current and former smokers
      recruited on a smoking cessation website. INTERVENTION: Participants were divided
      randomly into four groups, each of which received a unique message (in French) by
      e-mail. The 'control' message said that nicotine replacement therapy (NRT)
      attenuates withdrawal symptoms in smokers who want to quit. The 'temporary
      abstinence' message added that NRT can also be used by current smokers to manage
      smoke-free situations. The 'reduction' message indicated that NRT can be used by
      current smokers who do not want to quit but want to smoke fewer cigarettes. The
      'side-effects' message discouraged concomitant use of NRT and cigarettes.
      MEASUREMENTS: Perceived impact of these messages on motivation to quit smoking.
      FINDINGS: The e-mail was answered by 2027 people (25% of 8124 valid addresses).
      Smokers who received the 'reduction' message were slightly more likely than
      controls to report that this message increased their motivation to quit (66%
      versus 60%, P = 0.02). In contrast, smokers who received the 'side-effects'
      message were less likely than controls to report that this message increased
      their motivation (45% versus 60%, P < 0.001). The 'temporary abstinence' message
      had no detectable impact on motivation to quit. CONCLUSIONS: Among smokers
      recruited via a smoking cessation website, messages encouraging concomitant use
      of NRT and cigarettes may have either no effect or a positive effect on
      motivation to quit smoking.

PMID- 12814501
TI  - Perceived functions predict intensity of use and problems in young polysubstance
      users.
AB  - AIMS: To model consumption patterns and problems associated with alcohol,
      cannabis, ecstasy, amphetamine and cocaine hydrochloride use in a non-treatment
      sample of young polysubstance users. DESIGN: A cross-sectional survey of 364 16
      22-year-old (56.3% male) polysubstance users recruited and interviewed by peer
      interviewers. MEASUREMENTS: Structured questionnaires were used to gather
      identical datasets on the five target psychoactive substances, recording patterns
      of substance use; adverse consequences from use; negative effects; functions for
      substance use; and perceived peer use. FINDINGS: Functions for substance use
      strongly predicted intensity of use in all five substances when peer use, age of
      first use and demographics were controlled, explaining an additional 11-19% of
      the variance in scores. Functions also explained an average of 22% of the
      variance in problem scores over and above the effects of background variables and
      current intensity of use. In particular, functions concerned with relief from
      negative mood states were strong predictors of problem scores in alcohol,
      cannabis and cocaine. CONCLUSIONS: The potential implications of using a
      functional approach to explaining and responding to substance use are
      considerable. This could help to enhance our understanding of how experimental
      substance use becomes regular and how regular use becomes problematic, and could
      thus inform prevention, education and intervention efforts.

PMID- 12814502
TI  - Disability payments, drug use and representative payees: an analysis of the
      relationships.
AB  - AIMS: This study attempted to determine: if US federal cash disability payments
      increase the use of cocaine or opiates among those requalifying for supplemental
      security income (SSI) disability benefits compared with those who lost benefits;
      if drug use peaks at the beginning of the month after the receipt of the
      disability cash disbursement; and if money management by representative payees of
      requalifying SSI recipients suppresses drug use. DESIGN: A multi-site,
      prospective, 2 year longitudinal design was used with follow-up interviews
      conducted every 6 months. Urine samples were collected at the final three follow
      up interviews. SETTING: Data were collected in Chicago, IL, Los Angeles, CA, and
      Seattle, WA, USA. PARTICIPANTS: This study used a randomly selected sample of 740
      former recipients of SSI who had received disability benefits for drug addiction
      and alcoholism (DA&A) in 1996, were between the ages of 21 and 59 years, had not
      received concurrent social security disability insurance and provided testable
      urine samples and complete self-report data for at least one follow-up interview.
      MEASUREMENTS: Independent variables included demographics, SSI status at follow
      up, representative payee status, drug treatment participation and income. Time of
      drug testing was operationalized as the first 10 days of the month versus the
      last 20-21 days based on when the urine sample was collected. The dependent
      variables were cocaine and opiate use, determined by urinalysis results.
      FINDINGS: Participants were 28% more likely to test positive for cocaine use in
      the first 10 days of the month than later in the month. This effect was general
      across all subjects and was not restricted to those receiving SSI benefits. No
      such effect was found for opiate use. Receiving SSI benefits did not increase
      cocaine or opiate use generally, nor did having a representative payee suppress
      use. CONCLUSIONS: The findings do not support the contentions that federal cash
      benefits appreciably increase drug use or that representative payees discourage
      use, at least when use is defined dichotomously. The 'check effect' for cocaine
      use appears to be general and not confined to those receiving federal cash
      benefits. The lack of a 'check effect' for opiate use is probably the result of
      the difference between a relatively steady state of opiate use associated with
      addiction and a binge pattern of cocaine use triggered by suddenly flush
      resources.

PMID- 12814503
TI  - Dealing with the offer of drugs: the experiences of a sample of pre-teenage
      schoolchildren.
AB  - AIMS: To investigate the ways in which pre-teenage children anticipate and deal
      with the offer of drugs. DESIGN: A qualitative study based on semi-structured
      interviews with 10-12-year-old schoolchildren. SETTING: The cities of Glasgow
      (Scotland) and Newcastle (England), UK. PARTICIPANTS: A sample of 216 pre-teenage
      children. Forty-three had used drugs on at least one occasion, 42 had been
      offered but had not used drugs and 131 had neither used drugs nor been offered
      them. Most of the results reported in the paper relate to the experiences of the
      42 children who had declined the offer of drugs. FINDINGS: While children who had
      not been exposed to drug offers expressed a high degree of confidence in their
      ability to deal with them, those who had actually had to cope with such offers
      experienced a variety of difficulties. The ease with which an offer could be
      declined appeared to depend upon two main factors: who was making the offer and
      the context in which it was being made. According to the children, offers from
      people with whom they had a close relationship and those in which pressure or
      encouragement were involved were particularly difficult to deal with.
      CONCLUSIONS: The paper concludes that there is a need to equip young people
      better with the interpersonal tools they require to deal with the various
      situations they are likely to encounter in which drugs may be offered. It is
      suggested that a broadly based life skills approach to drug education may provide
      the best way of helping young people to deal with these situations.

PMID- 12814504
TI  - Amount of self-reported illicit drug use compared to quantitative hair test
      results in community-recruited young drug users in Amsterdam.
AB  - AIMS: To assess the dose-effect relationship between self-reported drug intake
      and the concentration of drugs and/or their metabolites in hair and to examine
      factors that may mediate this relationship. DESIGN AND SETTING: A cohort study
      among young drug users (YDU) in Amsterdam, the Netherlands, which began in July
      2000. At intake, YDU were asked to report their average drug intake over a 2
      month period. A hair sample was taken and then analysed for cocaine,
      benzoylecgonine (BE), morphine, 6-monoacetylmorphine and methadone. Weighted
      least-squares regression analysis was used to model hair-test results as a
      function of reported drug use. PARTICIPANTS: Subjects were 95 YDU (using cocaine,
      heroin, methadone and/or amphetamines at least 3 days/week) aged 18-30 residing
      in Amsterdam in 2000-2001. FINDINGS: Of the 95 YDU, one-third were women; mean
      age was almost 26; 30% had black hair, 33% blond hair and 37% brown hair. Cocaine
      use was reported by 92%, heroin by 75% and methadone by 64% of participants. All
      hair samples contained one or more drugs. Crude correlation coefficients between
      reported drug doses and drug concentrations in hair ranged between 0.45 and 0.59.
      The multivariate regression analysis showed that, for one or more types of drug,
      black-haired people, women and non-western European people had relatively high
      drug concentrations in hair (significant slope effects). The corresponding
      multivariate correlation coefficients ranged between 0.63 and 0.87. CONCLUSIONS:
      Hair testing can be used to quantify drug use in epidemiological studies, given
      that factors such as hair colour and sex are taken into account.

PMID- 12814505
TI  - The role of methadone in drug-related deaths in the west of Scotland.
AB  - AIMS: To determine the incidence of methadone as either the principal cause of
      death or as a contributing factor in drug related deaths in the Strathclyde
      Police region of Scotland and to assess the impact of supervised consumption of
      methadone on the number of deaths that occurred within each health board area
      within this region. DESIGN: Retrospective analysis of records held within the
      Department of Forensic Medicine and Science based at the University of Glasgow
      over the 11-year period 1991-2001. SETTING: The Strathclyde Police region of
      Scotland (population approximately 2.25 million). FINDINGS: In 1991, there was
      one death recorded which was attributable to methadone. Following the
      introduction of the methadone maintenance programme (MMP) in Glasgow during 1994,
      there was a 100% increase in these deaths compared to the previous year, a trend
      which continued over the subsequent 2 years. Following a confidential enquiry
      into these deaths and a greater compliance from pharmacies supervising methadone
      consumption, deaths involving methadone had decreased by 48% in 1997. This was
      particularly evident in the Greater Glasgow Health Board Area, where methadone
      prescribing has continued to rise annually. However, some difficulties still
      exist. Multiple take home doses are sometimes prescribed when a pharmacy is
      closed, which may lead to inadvertent overdose or facilitate diversion of
      legitimate supplies. In addition, continued use of heroin was found in
      approximately one-fifth of MMP patients, suggesting possible underdosing.
      CONCLUSIONS: A growing prevalence of heroin misuse has resulted in an increase in
      the number of individuals entering the MMP. Despite a continuing increase in the
      amount of methadone prescribed, methadone deaths in Strathclyde have decreased
      since 1996 due possibly to changes in both prescribing and clinical care. With
      efficient management to establish that the patient is complying with the
      guidelines of the programme and has stopped heroin misuse, methadone can be a
      safe drug for substitution therapy.

PMID- 12814506
TI  - Cannabis, ecstasy/MDMA and memory: a commentary on Simon & Mattick's recent
      study.

PMID- 12814519
TI  - Of mice and men: phylogenetic footprinting aids the discovery of regulatory
      elements.
AB  - Phylogenetic footprinting is an approach to finding functionally important
      sequences in the genome that relies on detecting their high degrees of
      conservation across different species. A new study shows how much it improves the
      prediction of gene-regulatory elements in the human genome.

PMID- 12814520
TI  - The influence of calcium and magnesium in drinking water and diet on
      cardiovascular risk factors in individuals living in hard and soft water areas
      with differences in cardiovascular mortality.
AB  - BACKGROUND: The role of water hardness as a risk factor for cardiovascular
      disease has been widely investigated and evaluated as regards regional
      differences in cardiovascular disease. This study was performed to evaluate the
      relation between calcium and magnesium in drinking water and diet and risk
      factors for cardiovascular disease in individuals living in hard and soft water
      areas with considerable differences in cardiovascular mortality. METHODS: A
      random sample of 207 individuals living in two municipalities characterised by
      differences in cardiovascular mortality and water hardness was invited for an
      examination including a questionnaire about health, social and living conditions
      and diet. Intake of magnesium and calcium was calculated from the diet
      questionnaire with special consideration to the use of local water. Household
      water samples were delivered by each individual and were analysed for magnesium
      and calcium. RESULTS: In the total sample, there were positive correlations
      between the calcium content in household water and systolic blood pressure (SBP)
      and negative correlations with s-cholesterol and s-LDL-cholesterol. No
      correlation was seen with magnesium content in household water to any of the risk
      factors. Calcium content in diet showed no correlation to cardiovascular risk
      factors. Magnesium in diet was positively correlated to diastolic blood pressure
      (DBP). In regression analyses controlled for age and sex 18.5% of the variation
      in SBP was explained by the variation in BMI, HbA1c and calcium content in water.
      Some 27.9% of the variation in s-cholesterol could be explained by the variation
      in s-triglycerides (TG), and calcium content in water. CONCLUSIONS: This study of
      individuals living in soft and hard water areas showed significant correlations
      between the content of calcium in water and major cardiovascular risk factors.
      This was not found for magnesium in water or calcium or magnesium in diet.
      Regression analyses indicated that calcium content in water could be a factor in
      the complexity of relationships and importance of cardiovascular risk factors.
      From these results it is not possible to conclude any definite causal relation
      and further research is needed.

PMID- 12814521
TI  - Bioelectronic DNA detection of human papillomaviruses using eSensor: a model
      system for detection of multiple pathogens.
AB  - BACKGROUND: We used human papillomaviruses (HPV) as a model system to evaluate
      the utility of a nucleic acid, hybridization-based bioelectronic DNA detection
      platform (eSensor) in identifying multiple pathogens. METHODS: Two chips were
      spotted with capture probes consisting of DNA oligonucleotide sequences specific
      for HPV types. Electrically conductive signal probes were synthesized to be
      complementary to a distinct region of the amplified HPV target DNA. A portion of
      the HPV L1 region that was amplified by using consensus primers served as target
      DNA. The amplified target was mixed with a cocktail of signal probes and added to
      a cartridge containing a DNA chip to allow for hybridization with complementary
      capture probes. RESULTS: Two bioelectric chips were designed and successfully
      detected 86% of the HPV types contained in clinical samples. CONCLUSIONS: This
      model system demonstrates the potential of the eSensor platform for rapid and
      integrated detection of multiple pathogens.

PMID- 12814523
TI  - Pancreatic cancer: new strategies available, but long battle ahead.

PMID- 12814522
TI  - Functional interaction between RNase III and the Escherichia coli ribosome.
AB  - BACKGROUND: RNase III is a dsRNA specific endoribonuclease which is involved in
      the primary processing of rRNA and several mRNA species in bacteria. Both primary
      structural elements and the secondary structure of the substrate RNA play a role
      in cleavage specificity. RESULTS: We have analyzed RNase III cleavage sites
      around both ends of pre-23 S rRNA in the ribosome and in the protein-free pre
      rRNA. It was found that in the protein-free pre-23 S rRNA the main cleavage site
      is at position (-7) in respect of the mature 5' end. When pre-23 S rRNA was in 70
      S ribosomes or in 50 S subunits, the RNase III cleavage occurred at position (
      3). We have demonstrated that RNase III interacts with both ribosomal subunits
      and with even higher affinity with 70 S ribosomes. Association of RNase III with
      70 S ribosomes cannot be dissociated by poly(U) RNA indicating that the binding
      is specific. CONCLUSIONS: In addition to the primary and secondary structural
      elements in RNA, protein binding to substrate RNA can be a determinant of the
      RNase III cleavage site.

PMID- 12814524
TI  - Decrease of ethanol intake following repeated injection of serotonin-1A agonist
      in rats: relationship with receptor responsiveness.
AB  - OBJECTIVE: To monitor pre and postsynaptic receptor responsiveness and
      consumption of ethanol following the repeated administration of a selective
      serotonin-1A receptor agonist, 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT),
      to ethanol treated rats. DESIGN: The experimental protocol was designed to
      administer ethanol orally to rats for three weeks and 8-OH-DPAT during the 3rd
      week. PLACE AND DURATION OF STUDY: The experiments were performed in the
      department of Biochemistry, Karachi University. Samples collected after three
      weeks of treatment were analyzed within a week. SUBJECTS AND METHODS: The study
      was conducted on 24 males albino Wistar rats treated with ethanol for three
      weeks. 8-OH-DPAT at a dose of 1mg/kg or saline was injected to ethanol treated
      rats from day 1 to day 5 during the 3rd week to monitor the effects on ethanol
      consumption. Pre and postsynaptic responses to 8-OH-DPAT were monitored by
      injecting the drug on the 6th day to a group of 5-day saline and a group of 5-day
      8-OH-DPAT injected animals. Control animals of the two groups were injected with
      saline. RESULTS: Before the injection of 8-OH-DPAT, weekly intakes of ethanol
      were highly comparable in the two groups. Administration of 8-OH-DPAT, from day 1
      to day 5, decreased ethanol intake. Pre and postsynaptic serotonin-1A receptor
      dependent responses monitored on the 6th day were higher in 5-day saline than 5
      day 8-OH-DPAT injected animals. CONCLUSION: A decrease in the effectiveness of
      negative feedback control over the synaptic availability of serotonin following 5
      day administration of 8-OH-DPAT is involved in the decreases of ethanol
      consumption.

PMID- 12814525
TI  - Myocardial preservation with intermittent aortic cross-clamping technique during
      coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate the safety and efficacy of intermittent aortic cross
      clamping technique for myocardial preservation during coronary artery bypass
      grafting and to compare the results with other published series using the same
      technique. DESIGN: An institution-based analytical study. PLACE AND DURATION OF
      STUDY: Study was carried out from July 1995 to December 1997 at Punjab Institute
      of Cardiology, Lahore. PATIENTS AND METHODS: The data of 100 consecutive patients
      were analyzed who had coronary artery bypass grafting without cardioplegia using
      intermittent aortic cross-clamping. All the patients who had emergency or
      concomitant major surgery, reoperations, and aortic disease with calcification
      were excluded from this study. RESULTS: Despite minor complications there was no
      mortality, no rhythm disturbance or perioperative infarction. Inotropic support
      was needed in 8% of patients. CONCLUSION: Our results compared favourably with
      other published series using the same technique. These results provide re
      assurance that intermittent aortic cross-clamping provides excellent myocardial
      protection and operative conditions for primary coronary artery bypass. It also
      provides a simple and safe option for myocardial protection during coronary
      artery bypass grafting.

PMID- 12814526
TI  - Laboratory profile in patients of cutaneous leishmaniasis from various regions of
      Pakistan.
AB  - OBJECTIVE: To delineate the different laboratory findings in patients of
      cutaneous leishmaniasis and to see the efficacy of some recent immunodiagnostic
      tools in the diagnosis of disease. DESIGN: Descriptive case-control study. PLACE
      AND DURATION OF STUDY: The study was conducted over a period of two years in
      Military Hospital (MH) and Armed Forces Institute of Pathology (AFIP),
      Rawalpindi, Pakistan. PATIENTS AND METHODS: Fifty patients with clinical
      diagnosis of cutaneous leishmaniasis(CL), were included in the study from
      western, south-western and northern regions of the country (Quetta, Multan,
      Chakwal, Kohat, Northern areas and Islamabad). Complete blood picture, blood
      groups, skin slit smears, impression smears and skin biopsies and serological
      tests including Enzyme-linked immunosorbent assay (ELISA), indirect fluorescent
      antibody test (IFAT), and indirect hemagglutination assay (IHA) were done in all
      cases. Immunohistochemistry with IFAT was performed in 20 patients and kDNA
      (kinetoplast DNA) probes in 16 patients. These tests were then evaluated to see
      their efficacy in diagnosis of CL. RESULTS: Blood CP was normal except for low
      hemoglobin levels. Most prevalent blood group was B-positive. Skin slit smear and
      impression smears were positive in 30% and 36% cases respectively. On
      histopathology four distinct histological patterns emerged. Results with H&E,
      Giemsa and Leishman stains were similar (36%) and PAS failed to stain parasite.
      On tissue section IFAT yielded 36%, peroxidase-antiperoxidase (PAP) 45% and kDNA
      probes 25% positive results. Serology was positive in 56% with ELISA, in 50% each
      with IFAT and IHA tests. CONCLUSION: Routine blood tests have no role in
      diagnosis of CL. Skin slit smear and touch impression smears are rapid means of
      diagnosis. Modern immunodiagnostic methods can produce better results but these
      are costly and availability is limited. In our setup slit skin smear/impression
      smear and light microscopy with routine H and E staining are probably the most co
      effective accurate diagnostic methods.

PMID- 12814527
TI  - Trial of extra amniotic saline infusion with oxytocin versus prostaglandin E2
      pessary for induction of labor.
AB  - OBJECTIVE: To determine the effectiveness and safety of cost-effective extra
      amniotic saline infusion (EASI) and simultaneous intravenous oxytocin infusion
      versus prostaglandin E2 vaginal pessary (PGE2) for induction of labor. DESIGN:
      Prospective randomized comparative study. PLACE AND DURATION OF STUDY: Labor room
      at the Mother and Child Health Centre, PIMS, Islamabad from September 2000 to
      December 2001. SUBJECTS AND METHODS: Women with singleton alive pregnancies and
      Bishop score < or =6, requiring induction of labor at > or =37 weeks gestation
      were randomly assigned to induction either with PGE2 3 mg vaginal pessary in two
      doses 6 hourly or EASI for 12 hours with simultaneous intravenous oxytocin
      infusion. Artificial rupture of membranes was done 12 hours post-induction and
      oxytocin infusion started in PGE2. Main outcome measures were induction delivery
      interval and the mode of delivery. Secondary outcome measures were the change in
      modified Bishop score 6 hours postinduction and neonatal outcome in the two
      induction modes. RESULTS: After 4 exclusions, 100 women were recruited in each
      arm. Mean induction delivery interval was 11.1 and 14.3 hours (p=.00) in PGE2 and
      EASI respectively. The cesarean rate was 11% and 15% (p=0.4) in PGE2 and EASI
      respectively. Mean Bishop score at induction was 3.2 in PGE2 and 3.1 in EASI,
      while after 6 hours it was 4.8 and 6.8 (p=0.00) respectively. Mean APGAR scores
      at 1 and 10 minutes were identical that is 6.2 and 8.6 respectively. CONCLUSION:
      Both the modes of induction were equally safe and effective in terms of the mode
      of delivery and APGAR score. EASI, however, had more rapid cervical ripening and
      shorter induction delivery interval.

PMID- 12814528
TI  - A 12 years audit of upper gastrointestinal endoscopic procedures.
AB  - OBJECTIVE: Evaluation of upper gastrointestinal (GI) endoscopy in terms of
      indications, diagnostic efficacy, and diseases diagnosed. DESIGN: Retrospective,
      observational case series. PLACE AND DURATION OF STUDY: DHQ Teaching Hospital,
      Rawalpindi, from March 1990 to December 2001. SUBJECTS AND METHODS: Patients who
      underwent upper GI endoscopy in 12 years were included. Upper GI endoscopies were
      performed according to standard protocol. Endoscopic diagnoses were based on
      widely accepted criteria. RESULTS: Of the 8481 patients, 4935 (58.2%) were female
      and 3546 (41.8%) male. Mean patient age was 40.5 years. Dyspepsia (42.6%), upper
      GI bleed (32.8%), and evaluation of chronic liver disease (10.2%) were common
      indications of the procedure. An endoscopic diagnosis was possible in 82.6%
      patients. Varices, gastritis, duodenitis, and combined lesions were common
      endoscopic diagnosis. Gastritis and duodenitis were most frequent causes of upper
      GI bleed. We noted more gastric ulcers compared to duodenal ulcers. Females had
      significantly more normal endoscopies, p-value=0.02. CONCLUSION: Upper GI
      endoscopy is an effective procedure. Dyspepsia evaluation is commonest indication
      for upper GI endoscopy in our patients. Etiology of upper GI bleed, and incidence
      of duodenal ulcer compared to gastric ulcer in our patients are different than
      described in literature. Females have significantly more normal endoscopies.

PMID- 12814529
TI  - Endoscopic retrograde cholangiopancreatographic evaluation of patients with
      obstructive jaundice.
AB  - OBJECTIVE: To evaluate the role of endoscopic retrograde cholangiopancreatography
      (ERCP) in patients with obstructive jaundice. DESIGN: A retrospective,
      observational study. PLACE AND DURATION OF STUDY: The study was carried out at
      Valley Clinic, Rawalpindi, from January 1999 to January 2002. SUBJECTS AND
      METHODS: Two-hundred and twenty-six patients, who underwent ERCP for evaluation
      of obstructive jaundice were included. ERCP in each case was performed with
      standard technique and the findings were recorded. Therapeutic procedures like
      sphincterotomy, Dormia extraction for stone, and stent placements were performed
      whenever indicated. RESULTS: Of the 226 patients, 117 (51.8%) were males, and 109
      (48.2%) females, their mean age being 51.8+/-16.6 years. Common bile and
      pancreatic ducts were visualized in 81.8% and 68.1% patients respectively.
      Growth/masses and stones were commonest causes of obstructive jaundice.
      Choledocholithias was common in males, while biliary channel related
      growth/masses were common in females (p-value=0.03). Common bile duct stone
      clearance rate was 88%, stenting was highly successful in patients with growth
      and strictures. ERCP related complications were noted in 11 (4.8%) patients.
      CONCLUSION: ERCP is an important diagnostic and therapeutic modality for
      evaluation of patients with obstructive jaundice. Growth/masses and stones are
      common causes of obstructive jaundice which can be diagnosed and treated with
      ERCP.

PMID- 12814530
TI  - Metabolic and clinical effects of Ramadan fasting in patients with type II
      diabetes.
AB  - OBJECTIVE: To evaluate the effects of fasting on anthropometric indices and
      carbohydrate and lipid metabolism in patients with type II diabetes. DESIGN:
      Observational non-interventional study. PLACE AND DURATION OF STUDY: : Diabetes
      clinic, Shariati Hospital, Tehran, Iran during Ramadan 1419 (winter 1998-99).
      PATIENTS AND METHODS: Fifty-seven volunteers with type II diabetes underwent
      anthropometric and biochemical evaluation before and on the 14th and 28th days of
      Ramadan. Biochemical markers were measured by standard laboratory methods and
      anthropometric indices by WHO criteria. Statistical analysis was done by ANOVA
      for repeated measurements and Friedman's two-way ANOVA using SPSSv6 software.
      RESULTS: Daily cholesterol intake increased in all subjects (p<0.03). Body mass
      index increased in women (p<0.03), but BMI and waist-hip ratio both decreased in
      men (p<0.01). Blood pressure, fasting blood glucose and serum fructosamine did
      not change during the study. Plasma insulin (p<0.05), C-peptide (p<0.01) and
      insulin resistance (p<0.01) decreased only in men. Total and LDL cholesterol
      increased significantly in all subjects during the study. CONCLUSION: Ramadan
      fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in
      patients with type II diabetes given appropriate dietary education and
      rescheduling of oral hypoglycaemic medication. Lipid profile is unfavourably
      altered due to changes in both diet and biochemical response to starvation.

PMID- 12814531
TI  - Role of cerebrospinal fluid diversion in posterior fossa tumor surgery.
AB  - OBJECTIVE: To assess the role of cerebrospinal fluid diversion in posterior fossa
      tumor surgery. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: This study
      was conducted at the Department of Neurosurgery, Pakistan Institute of Medical
      Sciences (PIMS), Islamabad from February 2000 to July 2002 over a period of two
      and-a-half years. SUBJECTS AND METHODS: Clinical, radiological and operative
      records of the patients who were operated for posterior fossa tumors were
      studied. Absolute and relative frequencies of the patients who were managed with
      external ventricular drainage (EVD) or ventriculoperitoneal shunt (VPS) were
      determined. Mean age and male to female ratio were also noted. RESULTS: There
      were 48 patients who were operated for posterior fossa tumors. Mean age was 23
      years. Male to female ratio was 1.2:1. VPS was done in 14 patients (29%) pre
      operatively, in one patient (2%) per-operatively and in 2 patients (4%)
      postoperatively. EVD was done in 33 patients out of whom 2 patients were shunted
      post-operatively. Sixty-five percent of the patients remained shunt-free.
      CONCLUSION: Although management of hydrocephalus secondary to posterior fossa
      tumors is controversial, majority of the patients need temporary cerebrospinal
      fluid diversion

PMID- 12814532
TI  - Infections in children with nephrotic syndrome.
AB  - OBJECTIVE: To determine the different types of infections in nephrotic children
      and their association with the activity of disease. DESIGN: A descriptive study.
      PLACE AND DURATION OF STUDY: It was carried out at National Institute of Child
      Health (NICH), Karachi from August 1995-July 1996. PATIENTS AND METHODS: All
      children with nephrotic syndrome who had various infections during the study
      period were evaluated for the activity of disease and type of infections.
      RESULTS: Out of 62 children with nephrotic syndrome having infections, 45
      (72.58%) were boys and 17 (27.42%) girls in a ratio of 2.5:1. Out of them 53
      (85.45%) were known nephrotics and 36 (58%) of them were on steroid therapy. Nine
      were new cases and had not received steroids. A total of 74 episodes of
      infections were observed in 62 children. Acute respiratory infections (ARI) and
      skin infections were the most common (29.27% and 27.02% respectively) followed by
      diarrhoea (13.51%), UTI (12.5%) and peritonitis (10.81%). Two patients had
      pulmonary tuberculosis and 3 patients had more than one infection (cellulitis,
      peritonitis and pneumonia). All children with cellulitis and peritonitis were in
      active disease, whereas more than 80% of patients with ARI, diarrhoea and UTI
      were having either relapse or had recent onset of disease. CONCLUSION: The study
      showed that ARI, cellulitis and diarrhoea were most common infections followed by
      UTI and peritonitis. Majority of the infections (>78%) were associated with
      active disease

PMID- 12814533
TI  - Role of digital rectal examination and prostate specific antigen in detecting
      carcinoma prostate.
AB  - OBJECTIVE: To investigate the ability of digital rectal examination (DRE) and
      prostate specific antigen (PSA) in detecting carcinoma prostate. DESIGN:
      Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: The study was
      conducted in the Department of Urology and Renal Transplantation from December
      1996 to December 1999. PATIENTS AND METHODS: Two hundred patients entered the
      protocol. They presented with complaint of prostatism or retention of urine. The
      patients were evaluated with estimation of serum prostate specific antigen and
      digital rectal examination was performed. Prostatic tissue biopsy was also done.
      RESULTS: Digital rectal examination has shown sensitivity of 63% and specificity
      of 73.22%. The sensitivity of PSA was 87% and specificity was 70.8%. The positive
      predictive value for DRE and PSA was 57.5% and 78.04% respectively. Negative
      predictive value was 73.22% and 85.22% respectively. P value was statistically
      significant <0.037. In the second part of study a baseline serum PSA level in age
      matched 200 patients without history of prostatism was estimated. CONCLUSION: It
      was concluded that PSA represent an important adjunct to DRE for detection of
      prostate carcinoma.

PMID- 12814534
TI  - Autopsy analysis in post-transplant patients--a basis for clinical audit.

PMID- 12814535
TI  - Congenital cystic adenomatoid malformation.
AB  - This case report presents the clinical picture, diagnostic methodology and
      surgical treatment of a female child who presented with chronic cough and
      dyspnoea due to congenital malformation of lung. A discussion of diagnosis and
      management is presented at the end.

PMID- 12814536
TI  - Leiomyoma of oesophagus.
AB  - We present a case of leiomyoma oesophagus which was presented in our surgical
      outpatient department with symptom of dysphagia for the last one year. Patient
      was investigated and diagnosed as a case of benign oesophageal neoplasm. She was
      successfully treated by transthoracic enucleation in our surgical unit at PIMS,
      Islamabad.

PMID- 12814537
TI  - Malrotation of the gut with tuberculous stricture.
AB  - Malrotation of the gut is a congenital anomaly of the gastrointestinal tract and
      usually present with obstruction in early childhood. Late presentation may come
      into light for associated pathology. We report a case that had developed
      obstruction due to tuberculous stricture and not due to the anomaly itself.

PMID- 12814538
TI  - Palliative surgery for advance osteosarcoma of shoulder region.
AB  - We are presenting here eight cases of advanced osteosarcoma of shoulder region
      involving scapula and upper humerus in children upto the age of thirteen years.
      All patients had complete loss of movement. Five patients underwent fore quarter
      amputation. Extensive amputation although a major mutilating procedure, provides
      patients a dramatic relief for the period that he survives.

PMID- 12814539
TI  - Prosthetic rehabilitation of an amputated thumb.
AB  - Prosthetic rehabilitation of any defect or abnormality of any part of the body
      must be as indiscernible as possible from the surrounding natural tissues in
      terms of cosmesis as well as function. Surgical procedures are more likely to
      meet the requirements of absolute function but the patients' involvement and
      willingness to undergo extensive and costly procedures like micro-surgical
      grafting and implants may preclude these procedures. This paper presents an
      alternative method of prosthetic rehabilitation of an amputated thumb with a heat
      cured silicone material.

PMID- 12814540
TI  - Repair of retrohepatic inferior vena cava injury.
AB  - A 10 years old child was brought to the Emergency Department of Combined Military
      Hospital (CMH), Lahore with a history of trivial injury due to fall from a
      bicycle. He was found to be having severe intraperitoneal hemorrhage. Immediate
      resuscitation in the emergency department could not revive his vital parameters.
      He was operated upon in emergency and found to be having grade V hepatic injury
      extending into retrohepatic inferior vena cava. Child was operated under general
      anesthesia and recovered well postoperatively without any residual complication.

PMID- 12814541
TI  - Retrocaval ureter.
AB  - Two cases of retrocaval ureter are reported. A 22 years old male patient
      presented to us with the complaints of right flank pain and hematuria and a child
      of 2 years referred to us for evaluation of right side moderate hydronephrosis
      detected on ultrasound. The diagnosis was confirmed on intravenous urography and
      retrograde pyelography. Both the ends were transected and anastomosed above a JJ
      stent in front of the inferior vena cava. Postoperatively the patients remained
      asymptomatic and the hydronephrosis improved.

PMID- 12814543
TI  - Dysfunctional families in Pakistan: physicians' perspective.

PMID- 12814542
TI  - Role of COX-2 specific inhibitors in oncogenesis.
AB  - Cyclooxygenase-2 (COX-2) is over expressed in a variety of premalignant and
      malignant conditions. It may contribute to carcinogenesis by modulating
      xenobiotic metabolism, apoptosis, immune surveillance, and angiogenesis.
      Selective COX-2 inhibitors suppress the formation of tumors in experimental
      models. Selective COX-2 inhibitors also suppress the growth and metastases of
      established tumors and enhance the anticancer activity of both radiotherapy and
      chemotherapy in experimental animals. This review aims at discussing evidence
      that inhibition of COX-2 represents a promising strategy to treat, prevent or
      possibly prevent human malignancies. Importantly, selective COX-2 inhibitors do
      not inhibit platelet function and cause fewer gastrointestinal side effects
      (peptic ulcer disease) than traditional nonsteroidal anti-inflammatory drugs
      (NSAIDS). More clinical trials are warranted to define the role of selective COX
      2 inhibitors in the prevention and treatment of cancer along with their
      assessment of toxicity.

PMID- 12814544
TI  - Multimodal spatial representations engaged in human parietal cortex during both
      saccadic and manual spatial orienting.
AB  - BACKGROUND: Recent neuroimaging studies have found that several areas of the
      human brain, including parietal regions, can respond multimodally. But given
      single-cell evidence that responses in primate parietal cortex can be motor
      related, some of the human multimodal activations might reflect convergent
      activation of potentially motor-related areas, rather than multimodal
      representations of space independent of motor factors. Here we crossed sensory
      stimulation of different modalities (vision or touch, in left or right hemifield)
      with spatially directed responses to such stimulation by different effector
      systems (saccadic or manual). RESULTS: The fMRI results revealed representations
      of contralateral space in both the posterior part of the superior parietal gyrus
      and the anterior intraparietal sulcus that activated independently of both
      sensory modality and motor response. Multimodal saccade-related or manual-related
      activations were found, by contrast, in different regions of parietal cortex.
      CONCLUSIONS: Whereas some parietal regions have specific motor functions, others
      are engaged during the execution of movements to the contralateral hemifield
      irrespective of both input modality and the type of motor effector.

PMID- 12814545
TI  - Negative regulation of yeast WASp by two SH3 domain-containing proteins.
AB  - BACKGROUND: WASp family proteins promote actin filament assembly by activating
      Arp2/3 complex and are regulated spatially and temporally to assemble specialized
      actin structures used in diverse cellular processes. Some WASp family members are
      autoinhibited until bound by activating ligands; however, regulation of the
      budding yeast WASp homolog (Las17/Bee1) has not yet been explored. RESULTS: We
      isolated full-length Las17 and characterized its biochemical activities on yeast
      Arp2/3 complex. Purified Las17 was not autoinhibited; in this respect, it is more
      similar to SCAR/WAVE than to WASp proteins. Las17 was a much stronger activator
      of Arp2/3 complex than its carboxyl-terminal (WA) fragment. In addition, actin
      polymerization stimulated by Las17-Arp2/3 was much less sensitive to the
      inhibitory effects of profilin compared to polymerization stimulated by WA
      Arp2/3. Two SH3 domain-containing binding partners of Las17, Sla1 and Bbc1, were
      purified and were shown to cooperate in inhibiting Las17 activity. The two SLA1
      SH3 domains required for this inhibitory activity in vitro were also required in
      vivo, in combination with BBC1, for cell viability and normal actin organization.
      CONCLUSIONS: Full-length Las17 is not autoinhibited and activates Arp2/3 complex
      more strongly than its WA domain alone, revealing an important role for the Las17
      amino terminus in Arp2/3 complex activation. Two of the SH3 domain-containing
      ligands of Las17, Sla1 and Bbc1, cooperate to inhibit Las17 activity in vitro and
      are required for a shared function in actin organization in vivo. Our results
      show that, like SCAR/WAVE, WASp proteins can be controlled by negative regulation
      through the combined actions of multiple ligands.

PMID- 12814546
TI  - Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick
      embryos.
AB  - BACKGROUND: The importance of endogenous antagonists in intracellular signal
      transduction pathways is becoming increasingly recognized. There is evidence in
      cultured mammalian cells that Pyst1/MKP3, a dual specificity protein phosphatase,
      specifically binds to and inactivates ERK1/2 mitogen-activated protein kinases
      (MAPKs). High-level Pyst1/Mkp3 expression has recently been found at many sites
      of known FGF signaling in mouse embryos, but the significance of this association
      and its function are not known. RESULTS: We have cloned chicken Pyst1/Mkp3 and
      show that high-level expression in neural plate correlates with active MAPK. We
      show that FGF signaling regulates Pyst1 expression in developing neural plate and
      limb bud by ablating and/or transplanting tissue sources of FGFs and by applying
      FGF protein or a specific FGFR inhibitor (SU5402). We further show by applying a
      specific MAP kinase kinase inhibitor (PD184352) that Pyst1 expression is
      regulated via the MAPK cascade. Overexpression of Pyst1 in chick embryos reduces
      levels of activated MAPK in neural plate and alters its morphology and retards
      limb bud outgrowth. CONCLUSIONS: Pyst1 is an inducible antagonist of FGF
      signaling in embryos and acts in a negative feedback loop to regulate the
      activity of MAPK. Our results demonstrate both the importance of MAPK signaling
      in neural induction and limb bud outgrowth and the critical role played by dual
      specificity MAP kinase phosphatases in regulating developmental outcomes in
      vertebrates.

PMID- 12814547
TI  - Dynamic alterations of replication timing in mammalian cells.
AB  - BACKGROUND: The eukaryotic genome is divided into distinct replication timing
      domains, which are activated during S phase in a strictly conserved order.
      Cellular differentiation can alter replication timing in some loci, but recent
      experiments yielded conflicting data regarding the relationship between gene
      expression and replication timing. The genetic and epigenetic determinants of
      replication timing in mammalian cells have yet to be elucidated. RESULTS: We
      developed a mammalian experimental system in which the timing of DNA replication
      can be altered in a controlled manner. This system utilizes sequences from the
      human beta-globin locus that exhibit orientation-dependent transcriptional
      silencing when inserted into the murine genome. We found that before insertion,
      the murine target site replicated late during S phase. After insertion,
      replication timing depended on the orientation of the transgene. In a
      transcription-permissive orientation, the transgene and flanking sequences
      replicated early. In the reverse (silencing-prone) orientation, these sequences
      replicated late. Early replication correlated with histone modifications of the
      transgene chromatin but could be observed in the absence of the beta-globin
      promoter. Importantly, the replication timing switch did not require a
      replication origin within the transgene. CONCLUSIONS: Transgene insertions into
      mammalian heterochromatin can alter the timing of DNA replication at the
      insertion site. This differentiation-independent replication timing switch did
      not necessitate insertion of an active promoter or a replication origin. These
      observations suggest that the timing of DNA replication can be manipulated by
      changes in DNA sequence, but that the determinants of replication timing are
      distinct from the sequences that specify replication initiation sites.

PMID- 12814548
TI  - Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle
      position in the early embryo.
AB  - BACKGROUND: Spindle positioning during an asymmetric cell division is of
      fundamental importance to ensure correct size of daughter cells and segregation
      of determinants. In the C. elegans embryo, the first spindle is asymmetrically
      positioned, and this asymmetry is controlled redundantly by two heterotrimeric
      Galpha subunits, GOA-1 and GPA-16. The Galpha subunits act downstream of the PAR
      polarity proteins, which control the relative pulling forces acting on the poles.
      How these heterotrimeric G proteins are regulated and how they control spindle
      position is still unknown. RESULTS: Here we show that the Galpha subunits are
      regulated by a receptor-independent mechanism. RNAi depletion of gpr-1 and gpr-2,
      homologs of mammalian AGS3 and Drosophila PINS (receptor-independent G protein
      regulators), results in a phenotype identical to that of embryos depleted of both
      GPA-16 and GOA-1; the first cleavage is symmetric, but polarity is not affected.
      The loss of spindle asymmetry after RNAi of gpr-1 and gpr-2 appears to be the
      result of weakened pulling forces acting on the poles. The GPR protein(s)
      localize around the cortex of one-cell embryos and are enriched at the posterior.
      Thus, asymmetric G protein regulation could explain the posterior displacement of
      the spindle. Posterior enrichment is abolished in the absence of the PAR polarity
      proteins PAR-2 or PAR-3. In addition, LIN-5, a coiled-coil protein also required
      for spindle positioning, binds to and is required for cortical association of the
      GPR protein(s). Finally, we show that the GPR domain of GPR-1 and GPR-2 behaves
      as a GDP dissociation inhibitor for GOA-1, and its activity is thus similar to
      that of mammalian AGS3. CONCLUSIONS: Our results suggest that GPR-1 and/or GPR-2
      control an asymmetry in forces exerted on the spindle poles by asymmetrically
      modulating the activity of the heterotrimeric G protein in response to a signal
      from the PAR proteins.

PMID- 12814549
TI  - Feedback contributions to visual awareness in human occipital cortex.
AB  - It has traditionally been assumed that processing within the visual system
      proceeds in a bottom-up, feedforward manner from retina to higher cortical areas.
      In addition to feedforward processing, it is now clear that there are also
      important contributions to sensory encoding that rely upon top-down, feedback
      (reentrant) projections from higher visual areas to lower ones. By utilizing
      transcranial magnetic stimulation (TMS) in a metacontrast masking paradigm, we
      addressed whether feedback processes in early visual cortex play a role in visual
      awareness. We show that TMS of visual cortex, when timed to produce visual
      suppression of an annulus serving as a metacontrast mask, induces recovery of an
      otherwise imperceptible disk. In addition to producing disk recovery, TMS
      suppression of an annulus was greater when a disk preceded it than when an
      annulus was presented alone. This latter result suggests that there are effects
      of the disk on the perceptibility of the subsequent mask that are additive and
      are revealed with TMS of the visual cortex. These results demonstrate spatial and
      temporal interactions of conscious vision in visual cortex and suggest that a
      prior visual stimulus can influence subsequent perception at early stages of
      visual encoding via feedback projections.

PMID- 12814550
TI  - Claudins in Caenorhabditis elegans: their distribution and barrier function in
      the epithelium.
AB  - Claudins ( approximately 23 kDa) with four transmembrane domains are major cell
      adhesion molecules working at tight junctions in vertebrates, where the
      intercellular space is tightly sealed (reviewed in ). We examined here the
      possible occurrence of claudin-like proteins in invertebrates, which do not bear
      typical tight junctions. Close blast searching of the C. elegans genome database
      identified four claudin-related, approximately 20-kDa integral membrane proteins
      (CLC-1 to -4), which showed sequence similarity to the vertebrate claudins. The
      expression and distribution of CLC-1 was then examined in detail by GFP
      technology as well as by immunofluorescence microscopy. CLC-1 was mainly
      expressed in the epithelial cells in the pharyngeal region of digestive tubes and
      colocalized with AJM-1 at their intercellular junctions. Then, to examine the
      possible involvement of CLC-1 in the barrier function, we performed RNA
      interference in combination with a tracer experiment: in CLC-1-deficient worms,
      the barrier function of the pharyngeal portion of the digestive tubes appeared to
      be severely affected. CLC-2 was expressed in seam cells in the hypodermis, and it
      also appeared to be involved in the hypodermis barrier. These findings indicated
      that multiple species of the claudin homologs, which are involved in the barrier
      function of the epithelium, exist in C. elegans.

PMID- 12814551
TI  - ATR kinase activity regulates the intranuclear translocation of ATR and RPA
      following ionizing radiation.
AB  - Upon damage of DNA in eukaryotic cells, several repair and checkpoint proteins
      undergo a dramatic intranuclear relocalization, translocating to nuclear foci
      thought to represent sites of DNA damage and repair. Examples of such proteins
      include the checkpoint kinase ATR (ATM and Rad3-related) as well as replication
      protein A (RPA), a single-stranded DNA binding protein required in DNA
      replication and repair. Here, we used a microscopy-based approach to investigate
      whether the damage-induced translocation of RPA is an active process regulated by
      ATR. Our data show that in undamaged cells, ATR and RPA are uniformly distributed
      in the nucleus or localized to promyelocytic leukemia protein (PML) nuclear
      bodies. In cells treated with ionizing radiation, both ATR and RPA translocate to
      punctate, abundant nuclear foci where they continue to colocalize. Surprisingly,
      an ATR mutant that lacks kinase activity fails to relocalize in response to DNA
      damage. Furthermore, this kinase-inactive mutant blocks the translocation of RPA
      in a cell cycle-dependent manner. These observations demonstrate that the kinase
      activity of ATR is essential for the irradiation-induced release of ATR and RPA
      from PML bodies and translocation of ATR and RPA to potential sites of DNA
      damage.

PMID- 12814552
TI  - Dual origin of the renal tubules in Drosophila: mesodermal cells integrate and
      polarize to establish secretory function.
AB  - Organs are made up of cells from separate origins, whose development and
      differentiation must be integrated to produce a physiologically coherent
      structure. For example, during the development of the kidney, a series of
      interactions between the epithelial mesonephric duct and the surrounding
      metanephric mesenchyme leads to the formation of renal tubules. Cells of the
      metanephric mesenchyme first induce branching of the mesonephric duct to form the
      ureteric buds, and they then respond to signals derived from them. As a result,
      mesenchymal cells are recruited to the buds, where they undergo a mesenchymal-to
      epithelial transition as they condense to form nephrons. In contrast, the simple
      renal tubules of invertebrates, such as insect Malpighian tubules (MpTs), have
      always been thought to arise from single tissue primordia, epithelial buds that
      grow by cell division and enlargement and from which a range of specialized
      subtypes differentiate. Here, we reveal unexpected parallels between the
      development of Drosophila MpTs and vertebrate nephrogenesis by showing that the
      MpTs also derive from two cell populations: ectodermal epithelial buds and the
      surrounding mesenchymal mesoderm. The mesenchymal cells are recruited to the
      growing tubules, where they undergo a mesenchymal-to-epithelial transition as
      they integrate and subsequently differentiate as a physiologically distinctive
      subset of tubule cells, the stellate cells. Strikingly, the normal incorporation
      of stellate cells and the later physiological activity of the mature tubules
      depend on the activity of hibris, an ortholog of mammalian NEPHRIN.

PMID- 12814553
TI  - The Drosophila embryonic patterning determinant torsolike is a component of the
      eggshell.
AB  - The development of the head and tail regions of the Drosophila embryo is
      dependent upon the localized polar activation of Torso (Tor), a receptor tyrosine
      kinase that is uniformly distributed in the membrane of the developing embryo.
      Trunk (Trk), the proposed ligand for Tor, is secreted as an inactive precursor
      into the perivitelline fluid that lies between the embryonic membrane and the
      vitelline membrane (VM), the inner layer of the eggshell. The spatial regulation
      of Trk processing is thought to be mediated by the secreted product of the
      torsolike (tsl) gene, which is expressed during oogenesis by a specialized
      population of follicle cells present at the two ends of the oocyte. We show here
      that Tsl protein is specifically localized to the polar regions of the VM in laid
      eggs. We further demonstrate that although Tsl can associate with nonpolar
      regions of the VM, the activity of polar-localized Tsl is enhanced, suggesting
      the existence of another spatially restricted factor acting in this pathway. The
      incorporation of Tsl into the VM provides a mechanism for the transfer of spatial
      information from the follicle cells to the developing embryo. To our knowledge,
      Tsl represents the first example of an embryonic patterning determinant that is a
      component of the eggshell.

PMID- 12814554
TI  - A persistent cellular change in a single modulatory neuron contributes to
      associative long-term memory.
AB  - Most neuronal models of learning assume that changes in synaptic strength are the
      main mechanism underlying long-term memory (LTM) formation. However, we show here
      that a persistent depolarization of membrane potential, a type of cellular change
      that increases neuronal responsiveness, contributes significantly to a long
      lasting associative memory trace. The use of a model invertebrate network with
      identified neurons and known synaptic connectivity had the advantage that the
      contribution of this cellular change to memory could be evaluated in a neuron
      with a known function in the learning circuit. Specifically, we used the well
      understood motor circuit underlying molluscan feeding and showed that a key
      modulatory neuron involved in the initiation of feeding ingestive movements
      underwent a long-term depolarization following behavioral associative
      conditioning. This depolarization led to an enhanced single cell and network
      responsiveness to a previously neutral tactile conditioned stimulus, and the
      persistence of both matched the time course of behavioral associative memory. The
      change in the membrane potential of a key modulatory neuron is both sufficient
      and necessary to initiate a conditioned response in a reduced preparation and
      underscores its importance for associative LTM.

PMID- 12814555
TI  - Role of VEGF-A in vascularization of pancreatic islets.
AB  - Blood vessel endothelium has been recently shown to induce endocrine pancreatic
      development. Because pancreatic endocrine cells or islets express high levels of
      vascular endothelial growth factors, VEGFs, we investigated the role of a
      particular VEGF, VEGF-A, on islet vascularization and islet function. By deleting
      VEGF-A in the mouse pancreas, we show that endocrine cells signal back to the
      adjacent endothelial cells to induce the formation of a dense network of
      fenestrated capillaries in islets. Interestingly, VEGF-A is not required for the
      development of all islet capillaries. However, the few remaining capillaries
      found in the VEGF-A-deficient islets are not fenestrated and contain an unusual
      number of caveolae. In addition, glucose tolerance tests reveal that the VEGF-A
      induced capillary network is not strictly required for blood glucose control but
      is essential for fine-tuning blood glucose regulation. In conclusion, we
      speculate that islet formation takes place in two sequential steps: in the first
      step, signals from blood vessel endothelium induce islet formation next to the
      vessels, and in the second step, the islets signal to the endothelium. The second
      step involves paracrine VEGF-A signaling to elaborate the interaction of islets
      with the circulatory system.

PMID- 12814556
TI  - Going, going, gone.
AB  - The decline and loss of species is inevitable in the face of growing human
      pressures on the environment but, according to one group of senior researchers, a
      standard framework is needed to assess the rate of this decline if researchers
      wish to be effective and policymakers are to take note.

PMID- 12814557
TI  - Plight of the bumblebee.
AB  - One group of insects highlight some of the potential economic damage that loss of
      biodiversity may entail for the future of human food crops.

PMID- 12814558
TI  - Homo gets a panning.
AB  - New studies suggesting that humans and chimpanzees deserve to share the same
      genus may do little to improve the parlous status of our relatives in their home
      environment.

PMID- 12814559
TI  - Say it with flowers.
AB  - Amongst Chelsea Flower Show's champion blooms last month, a range of diseased
      specimens helped flag up key plant research goals.

PMID- 12814560
TI  - The ecology, genetics and evolution of bacteria in an experimental setting.
AB  - Richard Lenski is the John Hannah Distinguished Professor of Microbial Ecology at
      Michigan State University. He studies the ecology, genetics and evolution of
      bacteria in an experimental setting that enables him to observe the dynamical
      processes and outcomes across many generations. One of his experiments with
      Escherichia coli has passed 30,000 generations and is still on-going. A few years
      ago, he also began studying artificial life in the form of 'digital organisms' -
      computer programs that replicate, mutate, compete, and therefore evolve and
      adapt.

PMID- 12814561
TI  - All of a flutter.

PMID- 12814562
TI  - ATM and ATR.

PMID- 12814563
TI  - Glia: much more than the neuron's side-kick.

PMID- 12814564
TI  - miRNAs: micro managers of programmed cell death.
AB  - Genomes encode numerous small RNAs, but the function of these molecules has been
      elusive. Recent studies show that two distinct microRNAs regulate programmed cell
      death, and provide new mechanisms for the regulation of animal development.

PMID- 12814565
TI  - Thermosensation: hot findings make TRPNs very cool.
AB  - TRPV and TRPM proteins have been shown to form temperature-responsive cation
      channels that act in nociception. Recent work on the mouse ANKTM1 and Drosophila
      Painless proteins shows that members of a third TRP subfamily, TRPN, also
      function in thermosensation.

PMID- 12814566
TI  - Wingless signaling: an axin to grind.
AB  - Negative regulation of Wingless/Wnt signaling plays an important role in
      embryonic patterning and is also needed for tumor suppression in adult tissues.
      New findings in Drosophila reveal a novel mechanism for down-regulating the
      activity of the Wingless/Wnt pathway.

PMID- 12814567
TI  - RNA repair: damage control.
AB  - RNA in a cell is subject to many of the same insults as DNA. RNA damage can
      induce apoptosis and may be exploited for anti-cancer chemotherapy. It is a
      surprise, however, to learn that cells may repair RNA damage, suggesting a far
      greater significance of RNA in genotoxic stress.

PMID- 12814568
TI  - Vascular patterning: more than just auxin?
AB  - The plant hormone auxin has long been known to play a pivotal role in vascular
      patterning and differentiation. But auxin is not the whole story: recent genetic
      analyses have identified additional factors required for vascular patterning, one
      of them involving sterols.

PMID- 12814569
TI  - Checkpoint mediators: relaying signals from DNA strand breaks.
AB  - The recently identified checkpoint mediator MDC1 facilitates recruitment of DNA
      repair proteins to damaged sites and establishment of the intra-S-phase cell
      cycle checkpoint. Increasing evidence suggests that proteins like MDC1 provide
      the framework necessary for transducing signals from DNA double-strand breaks.

PMID- 12814570
TI  - Epithelial morphogenesis: Netrin comes to a sticky and terminal end.
AB  - Netrin and its receptor Neogenin are thought to be regulators of axonal guidance
      in the nervous system. A recent report suggests they also play a role in
      epithelial morphogenesis.

PMID- 12814571
TI  - Drosophila morphogenesis: the Newtonian revolution.
AB  - Recent quantitative modeling of dorsal closure in the fruitfly Drosophila has
      revealed how multiple forces drive sealing of the two symmetrical epithelial
      sheets. A predictive model based on the new data allows gene function to be
      linked to the forces that drive tissue movement.

PMID- 12814572
TI  - Does excessive memory load attenuate activation in the prefrontal cortex? Load
      dependent processing in single and dual tasks: functional magnetic resonance
      imaging study.
AB  - Functional magnetic resonance imaging was used to investigate the relationship
      between cortical activation and memory load in dual tasks. An n-back task at four
      levels of difficulty was used with auditory-verbal and visual-nonverbal material,
      performed separately as single tasks and simultaneously as dual tasks. With
      reference to single tasks, activation in the prefrontal cortex (PFC) commonly
      increases with incremental memory load, whereas for dual tasks it has been
      hypothesized previously that activity in the PFC decreases in the face of
      excessive processing demands, i.e., if the capacity of the working memory's
      central executive system is exceeded. However, our results show that during both
      single and dual tasks, prefrontal activation increases continuously as a function
      of memory load. An increase of prefrontal activation was observed in the dual
      tasks even though processing demands were excessive in the case of the most
      difficult condition, as indicated by behavioral accuracy measures. The hypothesis
      concerning the decrease in prefrontal activation could not be supported and was
      discussed in terms of motivation factors. Similar changes in load-dependent
      activation were observed in two other regions outside the PFC, namely in the
      precentral gyrus and the superior parietal lobule. The results suggest that
      excessive processing demands in dual tasks are not necessarily accompanied by a
      diminution in cortical activity.

PMID- 12814573
TI  - Statistical tests for fMRI based on experimental randomization.
AB  - Statistical parametric mapping (SPM) analysis of fMRI data requires specifying
      correctly the temporal and spatial noise covariance structure. This is a
      difficult if not impossible task. When these assumptions are not satisfied,
      statistical inference can be invalid or inefficient. Permutation tests are free
      of strong assumptions on the distribution of signal noise. We propose permutation
      tests of fMRI data based on experimental randomization of the stimulus sequences.
      Smooth hemodynamic response curves are estimated using quadratic B-splines. We
      study fMRI data obtained from event-related potential (ERP) oddball paradigm.
      Tests of two-tone and three-tone stimulus sequences are conducted to illustrate
      the application of the proposed method. Comparisons of the SPM and proposed
      method show that a permutation test is more specific and less susceptible to
      artifacts.

PMID- 12814574
TI  - Subcortical, cerebellar, and magnetic resonance based consistent brain image
      registration.
AB  - A new landmark-initialized segmentation and intensity-based (LI-SI) inverse
      consistent linear elastic image registration algorithm is presented. This method
      uses manually identified landmarks, segmented volumetric (anatomical) structures,
      and normalized image signal intensity information to coregister datasets. The
      features used for image registration and evaluation include 35 cortical,
      cerebellar, and commissure landmarks manually identified by experts, subcortical
      and cerebellar regions defined semi-automatically by an artificial neural network
      and manually trimmed for validity by experts, and tissue classified images that
      were generated using a discriminant analysis of three magnetic resonance image
      sets representing T1, T2, and PD modalities. Four groups of results were computed
      for coregistering 16 datasets with the following registration techniques: rigid
      registration, extended Talairach registration, intensity-only inverse-consistent
      linear elastic registration, and the new LI-SI registration. Results are
      presented showing that relative overlap measurements increased as the
      dimensionality of the registration algorithm and amount of anatomical information
      increased. The average relative overlap improved from 0.53 for the rigid
      registration to 0.55 for the Talairach registration to 0.74 for the intensity
      only and to 0.85 for the LI-SI algorithm. We showed a statistically significant
      improvement for all but one structure using the intensity-only algorithm compared
      to the Talairach registration. Furthermore, statistically significant
      improvements for all structures were achieved using the LI-SI algorithm compared
      to the intensity-only algorithm.

PMID- 12814575
TI  - Separate neural pathways for contour and biological-motion cues in motion-defined
      animal shapes.
AB  - To determine whether contour and biological motion (BM) cues for motion-defined
      shapes are subserved by two separate mechanisms, we used PET to measure regional
      cerebral blood flow in nine human subjects. Subjects were scanned in the
      following four conditions: (1) contour-defined animals with natural movements
      (running), (2) motion-defined animals in which the contours were removed and dots
      were placed on the limbs and moving parts (BM; running); (3) drifting static
      animal shapes (contours); and (4) drifting dots. The results demonstrate that the
      perception of BM involves the superior frontal gyrus, the precuneus, the
      fusiform, the lingual and the medial temporal gyri, the inferior parietal lobe,
      the hippocampal and parahippocampal areas, and the cerebellum. In addition, the
      anterior cingulate cortex and the amygdala were significantly activated. The
      perception of contour-defined shapes produced significant elevation of rCBF in
      some areas similar to the BM condition, namely the fusiform, medial occipital,
      medial temporal, and lingual gyri. Only the occipital pole and the inferior
      temporal cortex were specifically activated by contour-defined shapes. These
      results are congruent with previous findings that the dorsal visual pathway is
      important for the perception of BM. They further support psychophysical results
      showing that contour and BM cues for motion-defined animal shapes are processed
      by independent channels.

PMID- 12814576
TI  - Independent component analysis of nondeterministic fMRI signal sources.
AB  - Neuronal activation can be separated from other signal sources of functional
      magnetic resonance imaging (fMRI) data by using independent component analysis
      (ICA). Without deliberate neuronal activity of the brain cortex, the fMRI signal
      is a stochastic sum of various physiological and artifact related signal sources.
      The ability of spatial-domain ICA to separate spontaneous physiological signal
      sources was evaluated in 15 anesthetized children known to present prominent
      vasomotor fluctuations in the functional cortices. ICA separated multiple
      clustered signal sources in the primary sensory areas in all of the subjects. The
      spatial distribution and frequency spectra of the signal sources correspond to
      the known properties of 0.03-Hz very-low-frequency vasomotor waves in fMRI data.
      In addition, ICA was able to separate major artery and sagittal sinus related
      signal sources in each subject. The characteristics of the blood vessel related
      signal sources were different from the parenchyma sources. ICA analysis of fMRI
      can be used for both assessing the statistical independence of brain signals and
      segmenting nondeterministic signal sources for further analysis.

PMID- 12814577
TI  - Functional magnetic resonance imaging (fMRI) "brain reading": detecting and
      classifying distributed patterns of fMRI activity in human visual cortex.
AB  - Traditional (univariate) analysis of functional MRI (fMRI) data relies
      exclusively on the information contained in the time course of individual voxels.
      Multivariate analyses can take advantage of the information contained in activity
      patterns across space, from multiple voxels. Such analyses have the potential to
      greatly expand the amount of information extracted from fMRI data sets. In the
      present study, multivariate statistical pattern recognition methods, including
      linear discriminant analysis and support vector machines, were used to classify
      patterns of fMRI activation evoked by the visual presentation of various
      categories of objects. Classifiers were trained using data from voxels in
      predefined regions of interest during a subset of trials for each subject
      individually. Classification of subsequently collected fMRI data was attempted
      according to the similarity of activation patterns to prior training examples.
      Classification was done using only small amounts of data (20 s worth) at a time,
      so such a technique could, in principle, be used to extract information about a
      subject's percept on a near real-time basis. Classifiers trained on data acquired
      during one session were equally accurate in classifying data collected within the
      same session and across sessions separated by more than a week, in the same
      subject. Although the highest classification accuracies were obtained using
      patterns of activity including lower visual areas as input, classification
      accuracies well above chance were achieved using regions of interest restricted
      to higher-order object-selective visual areas. In contrast to typical fMRI data
      analysis, in which hours of data across many subjects are averaged to reveal
      slight differences in activation, the use of pattern recognition methods allows a
      subtle 10-way discrimination to be performed on an essentially trial-by-trial
      basis within individuals, demonstrating that fMRI data contain far more
      information than is typically appreciated.

PMID- 12814578
TI  - Predicting events of varying probability: uncertainty investigated by fMRI.
AB  - Many everyday life predictions rely on the experience and memory of event
      frequencies, i.e., natural samplings. We used functional magnetic resonance
      imaging (fMRI) to investigate the neural substrates of prediction under varying
      uncertainty based on a natural sampling approach. The study focused particularly
      on a comparison with other types of externally attributed uncertainty, such as
      guessing, and on the frontomedian cortex, which is known to be engaged in many
      types of decisions under uncertainty. On the basis of preceding stimulus cues,
      participants predicted events that occurred with probabilities ranging from p =
      0.6 to p = 1.0. In contrast to certain predictions in a control task, predictions
      under uncertainty elicited activations within a posterior frontomedian area
      (mesial BA 8) and within a set of subcortical areas which are known to subserve
      dopaminergic modulations. The parametric analysis revealed that activation within
      the mesial BA 8 significantly increased with increasing uncertainty. A comparison
      with other types of uncertainty indicates that frontomedian correlates of
      frequency-based prediction appear to be comparable with those induced in long
      term stimulus-response adaptation processes such as hypothesis testing, in
      contrast to those engaged in short-term error processing such as guessing.

PMID- 12814579
TI  - Stepping stone sampling for retrieving artifact-free electroencephalogram during
      functional magnetic resonance imaging.
AB  - Ballistocardiogram and imaging artifacts cause major interference with
      simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging
      (fMRI) recording. In particular, the large amplitude of the imaging artifact
      precludes easy retrieval of EEG signals during fMRI scanning. Recording with
      20,000-Hz digitization rate combined with 3000-Hz low-pass filter revealed the
      real waveform of the imaging artifact, in which it was elucidated that each
      artifact peak precisely corresponded to each gradient component and actually had
      differential waveforms of the original gradient pulses. Based on this finding, to
      retrieve EEG signal during fMRI acquisition, a blip-type echo planar sequence was
      modified so that EEG sampling might be performed at every 1000 micros
      (digitization rate 1000 Hz) exclusively in the period in which the artifact
      resided around the baseline level. This method, called "stepping stone sampling,"
      substantially attenuated the amplitude of the imaging artifact. The remnant of
      the artifact was subtracted from the averaged artifact waveform. In human
      studies, alpha activity was successfully retrieved by inspection, and its
      attenuation/augmentation was observed during eyes open/closed periods. Fast
      Fourier transform analysis further revealed that even from DC up to 120 Hz,
      retrieved EEG data during scanning had very similar power distributions to the
      data retrieved during no scanning, implying the availability of the high
      frequency band of the retrieved EEG signals, including even the gamma band.

PMID- 12814580
TI  - Neural correlates underlying mental calculation in abacus experts: a functional
      magnetic resonance imaging study.
AB  - Experts of abacus operation demonstrate extraordinary ability in mental
      calculation. There is psychological evidence that abacus experts utilize a mental
      image of an abacus to remember and manipulate large numbers in solving problems;
      however, the neural correlates underlying this expertise are unknown. Using
      functional magnetic resonance imaging, we compared the neural correlates
      associated with three mental-operation tasks (numeral, spatial, verbal) among six
      experts in abacus operations and eight nonexperts. In general, there was more
      involvement of neural correlates for visuospatial processing (e.g., right
      premotor and parietal areas) for abacus experts during the numeral mental
      operation task. Activity of these areas and the fusiform cortex was correlated
      with the size of numerals used in the numeral mental-operation task.
      Particularly, the posterior superior parietal cortex revealed significantly
      enhanced activity for experts compared with controls during the numeral mental
      operation task. Comparison with the other mental-operation tasks indicated that
      activity in the posterior superior parietal cortex was relatively specific to
      computation in 2-dimensional space. In conclusion, mental calculation of abacus
      experts is likely associated with enhanced involvement of the neural resources
      for visuospatial information processing in 2-dimensional space.

PMID- 12814581
TI  - Spatial vs. object specific attention in high-order visual areas.
AB  - Recently we reported that the topographic organization of visual field
      eccentricity in human visual cortex extends into high-order, ventral
      occipitotemporal (VOT) cortex. Within this cortex, regions that respond
      preferentially to faces and buildings have specific eccentricity biases,
      suggesting that this category-eccentricity association may reflect differential
      needs of recognition processes. However, it is still not clear to what extent
      this center/periphery differentiation within high-order occipitotemporal cortex
      depends on immediate, moment-to-moment, task demands. Previous attention studies
      were confined either to exploring the visual field topography (spatial attention)
      or to object identity (object-based attention). Here, we combined the
      investigation of these two different attentional mechanisms in the same study. We
      found that the main source of attentional modulation in occipitotemporal cortex
      was object-based attention. Shifting attention to different object categories
      (buildings, faces, and arrows) substantially modulated the object-related
      activations. The differential activation to each object category in
      occipitotemporal object areas was maintained, albeit at a reduced level, even
      when attention was focused on different spatial locations. A slight eccentricity
      related attentional differentiation was observed in the more dorsal lateral
      occipital region, but not in the VOT cortex. These results argue against the
      possibility that the source of the eccentricity differentiation in VOT cortex is
      due solely to moment-to-moment shifts in spatial attention mechanism and supports
      the notion that the eccentricity-biased maps found in this region are due to
      built-in shape selectivity established over long-term processes.

PMID- 12814582
TI  - Complementary hemispheric specialization for word and accent detection.
AB  - When we hear a familiar word pronounced in a foreign accent, which parts of the
      brain identify the word and which identify the accent? Here we present converging
      evidence from PET blood flow, event-related scalp potentials, and behavioral
      responses during dichotic listening, showing homologous and complementary
      hemispheric specialization for word and accent detection. Accuracy of detecting
      target words was greater when stimuli were presented to the right ear, indicating
      left hemisphere specialization, with no ear advantage for detecting target
      accents. Detection of words also produced increased blood flow in a left frontal
      area associated with motor and phonetic processing, and a left temporal area
      associated with semantic memory. Homologous areas of the right hemisphere,
      together with right prefrontal and precuneus regions, showed increased blood flow
      during detection of accents. Separate analyses for each detection task indicated
      that voxels whose activity maximally correlated with accuracy were in the left
      hemisphere for word detection, but in the right hemisphere for accent detection.
      Voxels whose activity maximally correlated with inaccuracy were in the opposite
      hemisphere for both tasks, strengthening the interpretation that between-task
      differences in brain activation are related to lateralized specializations for
      task performance. ERP waveforms and reaction times suggested that greater left
      hemisphere activation during word detection preceded greater right hemisphere
      activation during accent detection. The results are interpreted as supporting
      left hemisphere specialization for extraction of the linguistic, phonetic, and
      semantic information contained in speech, and right hemisphere specialization for
      pragmatics, the social context of linguistic communication.

PMID- 12814583
TI  - Power grip disinhibits the ipsilateral sensorimotor cortex: a TMS and fMRI study.
AB  - Electrophysiological studies have shown that forceful activation of the hand
      muscles (power grip) is accompanied by an increased excitability of the
      ipsilateral corticospinal system. This increase in excitability may be due to
      spinal or cortical mechanisms. Here we show with fMRI that this phenomenon is at
      least in part mediated at a cortical level. We used TMS to show that the
      increased ipsilateral excitability during a forceful maneuver leads to enhanced
      stimulus-response curves. fMRI was used to compare the activation during a
      repetitive hand movement with or without an accompanying power grip on the
      opposite site. The power grip reduced movement-related activation in the
      ipsilateral sensorimotor cortex. Peak deactivation was located in the left
      postcentral gyrus extending into the adjacent precentral gyrus. This finding
      suggests that a forceful activation of the hand muscles disinhibits a distinct
      functional representation in the ipsilateral sensorimotor cortex. Consequently,
      the excitability of the corticospinal system increases and less neuronal
      excitatory activity is needed to perform a given task. The results may be
      important for a variety of studies as they suggest that fMRI may show decreased
      hemodynamic response under conditions in which other neurophysiological methods
      have shown increased functional activity.

PMID- 12814584
TI  - Estimation of bolus dispersion effects in perfusion MRI using image-based
      computational fluid dynamics.
AB  - Bolus tracking magnetic resonance imaging (MRI) is a powerful technique for
      measuring perfusion, and is playing an increasing role in the investigation of
      acute stroke. However, limitations have been reported when assessing patients
      with steno-occlusive disease. The presence of a steno-occlusive disease in the
      artery may cause bolus dispersion, which has been shown to introduce significant
      errors in cerebral blood flow (CBF) quantification. Bolus dispersion is commonly
      described by a vascular transport function, but the function that properly
      characterizes the dispersion is unknown. A novel method to quantify bolus
      dispersion errors on perfusion measurements is presented. A realistic patient
      specific model is constructed from anatomical and physiologic MR data, and the
      arterial blood flow pattern and the transport of the bolus of contrast agent are
      computed using finite element analysis. The methodology presented was used also
      to evaluate the accuracy of three simple vascular models. The methodology was
      tested on MR data from two normal subjects and two subjects with mild carotid
      artery stenosis. The estimated CBF errors were of the order of 15% to 20%.
      However, the presence of stenosis did not necessarily introduce larger dispersion
      (not only the geometrical model but also the particular physiologic conditions
      influence the degree of bolus dispersion). The method described will contribute
      to a better understanding of errors introduced by dispersion effects, to the
      assessment and validation of vascular models, and to the development of new
      methods for the correction of dispersion errors in CBF quantification.

PMID- 12814585
TI  - The impact of individual differences on the neural circuitry underlying sadness.
AB  - Several functional neuroimaging studies have been carried out in healthy subjects
      to investigate the neural correlates of sadness. Importantly, there is little
      consistency among the results of these studies. Hypothesizing that individual
      differences may account for the discrepancies among these investigations, we
      conducted two functional magnetic resonance imaging (fMRI) studies to identify
      the neural circuitry underlying this basic emotion. In these two methodologically
      identical studies, two different groups (n = 10 for each study) of healthy female
      subjects were scanned while they were experiencing a transient state of sadness
      induced by viewing sad film excerpts. In the first of these studies, sadness was
      correlated with significant loci of activation in the anterior temporal pole and
      insula (P < 0.05, corrected). In the second study, however, sadness was
      correlated with significant activation in the orbitofrontal and medial prefrontal
      cortices (P < 0.05, corrected). In addition, individual statistical parametric
      maps revealed a marked degree of interindividual variability in both Study 1 and
      Study 2. These results strongly support the view that individual differences may
      be responsible for the inconsistencies found in the literature regarding the
      neural substrates of sadness and of other basic emotions. These findings also
      suggest that individual data should be reported in addition to group data,
      because they provide useful information about the variability present in the
      subjects investigated and, thus, about the typicality and generalizability of the
      results.

PMID- 12814586
TI  - Sustained attention impairment correlates to gray matter decreases in first
      episode neuroleptic-naive schizophrenic patients.
AB  - Impaired sustained attention seems to be a specific neuropsychological deficit
      that is closely linked to schizophrenia. Voxel based morphometry has emerged as a
      useful tool for the detection of subtle gray matter (GM) abnormalities. The aim
      of our study was to identify the cerebral regions related to the Identical-Pair
      version of the Continuous Performance Test (CPT-IP) performance in schizophrenic
      patients. The study included 13 right-handed, male, first-episode, paranoic,
      neuroleptic-naive schizophrenic patients and 13 matched controls. High-resolution
      whole-brain MR images were segmented and analyzed for the whole brain and for
      regions of interest (ROI) using SPM99. Furthermore, the correlation between CPT
      IP performance and GM density was examined. Volumetric analysis of the thalami
      was also carried out. GM density analysis shown decreases in patients in anterior
      cingulate gyrus, left inferior frontal, right claustrum, left pulvinar, and
      dorsomedial bilateral thalamic nuclei, and caudate nuclei as well as left
      hippocampus and parahippocampal gyrus. Thalamic ROIs revealed a strong
      correlation between groups differences. The thalamic GM density allowed a good
      individual classification. GM increases were detected in left insula, superior
      temporal gyrus, and putamen nucleus, and right supramarginal gyrus. Schizophrenic
      patients showed smaller left and right thalamic volumes. We found that GM density
      of the left thalamic nucleus, left angular, and supramarginal gyrus, and left
      inferior frontal and postcentral gyri correlated significantly with CPT-IP
      performance in patients but not in controls. Moreover, the restricted ROIs
      regression was strongly significant for both left and right thalamus. In summary,
      we provide evidence for the involvement of thalamic, inferior-parietal, and
      frontal regions in the attentional deficits observed in schizophrenic patients.

PMID- 12814587
TI  - Attention as a characteristic of nonclinical dissociation: an event-related
      potential study.
AB  - Individual differences in dissociative style (which is generally considered a
      risk factor for dissociative pathology) were studied in a nonclinical sample. It
      was hypothesized that high-dissociative participants would show enhanced
      attentional abilities toward both relevant and irrelevant stimulus features. In
      the experiment, threatening and affectively neutral words were classified on
      their affective valence and the presence of the letter A. To facilitate the full
      deployment of dissociative abilities, a feature (i.e., negative valence) was
      included that would automatically attract attention but not interfere with the
      processing of the central feature. Both the behavioral measures (i.e., reaction
      time) and the central neural measures (i.e., event-related potentials) showed
      that the ability to direct attention to the central feature was enhanced in the
      high dissociators. The high dissociators, moreover, showed evidence of directing
      attention to both affective valence and the letter A in the letter detection
      task. It is concluded that dissociative style does not correspond to a damaged or
      disturbed function but to an enhanced ability to direct and divide attention.

PMID- 12814588
TI  - Automatic segmentation of thalamic nuclei from diffusion tensor magnetic
      resonance imaging.
AB  - The nuclei of the thalamus have traditionally been delineated by their distinct
      cyto/myeloarchitectural appearance on histology. Here, we show that diffusion
      tensor magnetic resonance imaging (DTI) can noninvasively resolve the major
      thalamic nuclei based on the characteristic fiber orientation of the
      corticothalamic/thalamocortical striations within each nucleus. Using an
      automatic clustering algorithm, we extracted the Talairach coordinates for the
      individual thalamic nuclei. The center-of-mass coordinates for the segmented
      nuclei were found to agree strongly with those obtained from a histological
      atlas. The ability to resolve thalamic nuclei with DTI will allow for
      morphometric analysis of specific nuclei and improved anatomical localization of
      functional activation in the thalamus.

PMID- 12814589
TI  - Impaired thalamocortical connectivity in humans during general-anesthetic-induced
      unconsciousness.
AB  - Whereas converging lines of evidence suggest that anesthetic-induced
      unconsciousness may result from disruption of functional interactions within
      neural networks involving the thalamus and cerebral cortex, the effects
      anesthetics have on human thalamocortical connectivity remain unexamined with
      current neuroimaging techniques. To address this issue we retrospectively
      analyzed positron emission tomography data from 11 volunteers scanned for
      regional cerebral glucose utilization (rCMRglu) when awake and again during
      isoflurane- (n = 6) or halothane- (n = 5) induced unconsciousness using
      statistical parametric mapping (SPM99) and structural equation modeling. A main
      effect analysis, contrasting awake and unconscious metabolic activity, localized
      a discrete region of the left va/vl thalamus whose relative rCMRglu activity was
      significantly suppressed (P < 0.05, corrected) during the unconscious state. To
      identify brain regions whose functional connectivity with this region of the
      thalamus was impaired during the unconscious state, a psychophysiological
      interaction analysis was performed. This analysis revealed effects predominantly
      in topographically related areas of the primary motor and supplementary motor
      association cortices. Structural equation modeling of a neuroanatomical network
      encompassing these empirically identified regions revealed significant state
      related changes in effective connectivity (chi(2)diff (6)-15.88; P < 0.05) which
      primarily involved impairment of thalamocortical and corticocortical projections
      during the unconscious state. These findings support the hypothesis that a
      mechanistic component underlying general-anesthetic-induced unconsciousness
      involves disruption of functional interactions within thalamocortical neural
      networks.

PMID- 12814590
TI  - Functional MRI using sensitivity-encoded echo planar imaging (SENSE-EPI).
AB  - Parallel imaging methods become increasingly available on clinical MR scanners.
      To investigate the potential of sensitivity-encoded single-shot EPI (SENSE-EPI)
      for functional MRI, five imaging protocols at different SENSE reduction factors
      (R) and matrix sizes were compared with respect to their noise characteristics
      and their sensitivity toward functional activation in a motor task examination.
      At constant echo times, SENSE-EPI was either used to shorten the single volume
      acquisition times (TR(min)) at matrix size 128 x 100 (22 slices) from 3.9 s (no
      SENSE) to 2.0 s at R = 3, or to increase the matrix size to 192 x 153 (22
      slices), resulting in TR(min) = 5.3 s for R = 2 or TR(min) = 3.4 s for R = 3. At
      the lower resolution, the bisection of echo train length (R = 2) substantially
      reduced distortions and blurring, while signal-to-noise and statistical power
      (measured by cluster size and maximum t value per unit time) were hardly reduced.
      At R = 3 the additional gain in speed and distortion reduction was quite small,
      while signal-to-noise and statistical power dropped significantly. With enhanced
      spatial resolution the time course signal-to-noise was better than expected from
      theory for purely thermal noise because of a reduced contribution of
      physiological noise, and statistical power almost reached that of the regular,
      low-resolution single-shot EPI, with a slight drop off toward R = 3. Thus, SENSE
      EPI allows to substantially increase speed and spatial resolution in fMRI. At
      SENSE reduction factors up to R = 2, the potential drawbacks regarding signal-to
      noise and statistical power are almost negligible.

PMID- 12814591
TI  - Estimation of general linear model coefficients for real-time application.
AB  - An algorithm using an orthogonalization procedure to estimate the coefficients of
      general linear models (GLM) for functional magnetic resonance imaging (fMRI)
      calculations is described. The idea is to convert the basis functions or
      explanatory variables of a GLM into orthogonal functions using the usual Gram
      Schmidt orthogonalization procedure. The coefficients associated with the
      orthogonal functions, henceforth referred to as auxiliary coefficients, are then
      easily estimated by applying the orthogonality condition. The original GLM
      coefficients are computed from these estimates. With this formulation, the
      estimates can be updated when new image data become available, making the
      approach applicable for real-time estimation. Since the contribution of each
      image data is immediately incorporated into the estimated values, storing the
      data in memory during the estimation process becomes unnecessary, minimizing the
      memory requirements of the estimation process. By employing Cholesky
      decomposition, the algorithm is a factor of two faster than the standard
      recursive least-squares approach. Results of the analysis of an fMRI study using
      this approach showed the algorithm's potential for real-time application.

PMID- 12814592
TI  - Optimized EPI for fMRI studies of the orbitofrontal cortex.
AB  - A common problem in gradient-echo echo planar imaging (EPI) is the occurrence of
      image distortions and signal losses caused by susceptibility gradients near
      air/tissue interfaces. Since EPI is frequently used for functional magnetic
      resonance imaging experiments based on the blood oxygenation level-dependent
      effect, functional studies of certain brain regions affected by susceptibility
      gradients, such as the temporal lobes and the orbitofrontal cortex, may be
      compromised. In this work a method for signal recovery in certain regions of the
      orbitofrontal cortex is presented. The influence of in-plane susceptibility
      gradients is reduced by optimization of the imaging slice orientation. Through
      plane susceptibility gradients are partly compensated by means of a moderate
      preparation gradient pulse similar to z-shimming. In contrast to several other
      techniques proposed in the literature for reducing susceptibility effects, this
      method does not compromise the temporal resolution and is therefore applicable to
      event-related studies.

PMID- 12814593
TI  - Estimation of the local statistical noise in positron emission tomography
      revisited: practical implementation.
AB  - The purpose of this report is to implement novel modifications to overcome the
      limitations of an existing algorithm for estimating the local statistical noise
      in a positron emission tomography (PET) image without performing repeated
      measures. The original algorithm is based on a modification of the filtered back
      projection algorithm that allows the variance to be estimated using only a single
      sinogram. In addition, the effects of photon absorption, random coincidences,
      radioactive decay, and detector nonuniformity are taken into account. However,
      there are some limitations when applying this method with modern scanners. In
      particular, it is common practice to interleave the projections in the sinogram
      (to increase the sampling rate along each projection) and to perform an
      interpolation when actually back-projecting to reconstruct the images. Both of
      these procedures introduce covariance among the elements of the projections,
      which is cumbersome and impractical to deal with using the existing technique for
      creating a variance image. An alternative image reconstruction scheme that is
      shown to be equivalent to image reconstruction using traditional filtered back
      projection greatly simplifies the estimation of the variance image. The proposed
      methods were tested by Monte Carlo simulations and by using repeated scans of a
      uniform phantom filled with F-18. Results demonstrate that the proposed methods
      are very rigorous and stable when compared to calculations of the local variance
      using either repeated measures with a large number of measurements, or region-of
      interest estimates of the variance, assuming homogeneous variance structure. In
      addition, strategies for extending the proposed technique are discussed that
      would permit the estimation of the variance due to measurement error of a pixel
      in a brain map from both single subjects and pooled group data.

PMID- 12814594
TI  - A report of the functional connectivity workshop, Dusseldorf 2002.
AB  - This report provides a commentary on the issues presented and discussed at the
      recent "Functional Brain Connectivity" workshop, held in Dusseldorf, Germany. The
      workshop brought together researchers using different approaches to study
      connectivity in the brain, providing them with an opportunity to share
      conceptual, mathematical, and experimental ideas and to develop strategies and
      collaborations for future work on functional integration. The main themes that
      emerged included: (1) the importance of anatomical knowledge in understanding
      functional interactions the brain; (2) the need to establish common definitions
      for terms used across disciplines; (3) the need to develop a satisfactory
      framework for inferring causality from functional imaging and EEG/MEG data; (4)
      the importance of analytic tools that capture the dynamics of neural
      interactions; and (5) the role of experimental paradigms that exploit the
      functional imaging of perturbations to cortical interactions.

PMID- 12814595
TI  - The elusive concept of brain connectivity.
AB  - Neurons and neural populations do not function as islands onto themselves.
      Rather, they interact with other such elements through their afferent and
      efferent connections in an orchestrated manner so as to enable different
      sensorimotor and cognitive tasks to be performed. The concept of functional
      connectivity and the allied notion of effective connectivity were introduced to
      designate the functional strengths of such interactions. Functional neuroimaging
      methods, especially PET and fMRI, have been used extensively to evaluate the
      functional connectivity between different brain regions. After providing a brief
      historical review of these notions of brain connectivity, I argue that the
      conceptual formulations of functional and effective connectivity are far from
      clear. Specifically, the terms functional and effective connectivity are applied
      to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG)
      that vary in spatial, temporal, and other features, using different definitions
      (even for data of the same modality) and employing different computational
      algorithms. Until it is understood what each definition means in terms of an
      underlying neural substrate, comparisons of functional and/or effective
      connectivity across studies may appear inconsistent and should be performed with
      great caution.

PMID- 12814597
TI  - The co-evolution of individual behaviors and social institutions.
AB  - We present agent-based simulations of a model of a deme-structured population in
      which group differences in social institutions are culturally transmitted and
      individual behaviors are genetically transmitted. We use a standard extended
      fitness accounting framework to identify the parameter space for which this co
      evolutionary process generates high levels of group-beneficial behaviors. We show
      that intergroup conflicts may explain the evolutionary success of both: (a)
      altruistic forms of human sociality towards unrelated members of one's group; and
      (b) group-level institutional structures such as food sharing which have emerged
      and diffused repeatedly in a wide variety of ecologies during the course of human
      history. Group-beneficial behaviors may evolve if (a) they inflict sufficient
      fitness costs on outgroup individuals and (b) group-level institutions limit the
      individual fitness costs of these behaviors and thereby attenuate within-group
      selection against these behaviors. Thus, the evolutionary success of individually
      costly but group-beneficial behaviors in the relevant environments during the
      first 90,000 years of anatomically modern human existence may have been a
      consequence of distinctive human capacities in social institution building.

PMID- 12814598
TI  - Optimal choice between feedforward and feedback control in gene expression to
      cope with unpredictable danger.
AB  - All organisms face risks of unpredictable danger caused by harmful physical
      environments, pathogens, parasites or predators. Organisms may have several
      alternative ways of coping with such dangers. These differ in cost, effectiveness
      and activation time. We study the conditions under which it is optimal to use
      different alternatives for damage control. As an example we consider a microbe
      (such as E. coli), which may experience heat shocks that cause denaturation of
      proteins in the cell. To restore the denatured proteins the organism produces
      heat-shock proteins (HSP). There are two different pathways for production of
      HSP. Some HSP are produced immediately after a heat shock (feedforward control),
      but additional HSP may be produced thereafter, stimulated by the presence of
      denatured proteins (feedback control). Feedforward is based solely on heat-shock
      intensity without accurate information on the resulting amount of denatured
      proteins. We examine the optimal combination of the two pathways that minimizes
      the sum of the damage caused by the presence of untreated denatured proteins and
      the production cost of HSP. The optimal response depends on the time delay for
      feedback control, the effectiveness of HSP in processing denatured proteins, the
      production cost of HSP, the severity of damage by denatured proteins and the
      probability distribution of the abundance of denatured protein conditional on
      heat-shock intensity. We find that feedforward control should always be used.
      Additional HSP may be produced by feedback control when the abundance of
      denatured protein is large whilst no feedback control should be used when it is
      small. All the HSP are produced by feedforward control when the maximum is close
      to the mean of denatured protein abundance conditional on the heat-shock
      intensity.

PMID- 12814599
TI  - Vector space classification of DNA sequences.
AB  - Revisiting the problem of intron-exon identification, we use a principal
      component analysis (PCA) to classify DNA sequences and present first results that
      validate our approach. Sequences are translated into document vectors that
      represent their word content; a principal component analysis then defines
      Gaussian-distributed sequence classes. The classification uses word content and
      variation of word usage to distinguish sequences. We test our approach with
      several data sets of genomic DNA and are able to classify introns and exons with
      an accuracy of up to 96%. We compare the method with the best traditional coding
      measure, the non-overlapping hexamer frequency count, and find that the PCA
      method produces better results. We also investigate the degree of cross
      validation between different data sets of introns and exons and find evidence
      that the quality of a data set can be detected.

PMID- 12814600
TI  - A study of prey-predator relations for mammals.
AB  - In this paper, we present a prey-predator nonlinear model for mammals, consisting
      of large- and small-size prey species with group defence, in a partially
      protected habitat. If the prey size is small, then it is more prone to the
      predator at higher densities. Conversely, large prey size at higher densities
      tend to develop group defence. Therefore, the predator will be attracted towards
      that area where prey are less in number. A new physical constant has been
      introduced into the radiation-type condition on that part of the boundary where
      interaction between prey and predator takes place. This constant allows us to
      efficiently model group defence capabilities of the herds and its numerical
      values have to be determined for different pairs of prey-predator species from
      field observations. A way of measuring the constants involved in the model is
      suggested. Numerical results are provided and thoroughly discussed for a habitat
      of circular shape. The obtained results show that in the region away from the
      protected area, the density of large-size prey species is higher than that of
      small-size prey species, a fact that is in accordance with observations.

PMID- 12814601
TI  - A flexible model of foraging by a honey bee colony: the effects of individual
      behaviour on foraging success.
AB  - This paper develops and explores a model of foraging in honey bee colonies. The
      model may be applied to forage sources with various properties, and to colonies
      with different foraging-related parameters. In particular, we examine the effect
      of five foraging-related parameters on the foraging response and consequent
      nectar intake of a homogeneous colony. The parameters investigated affect
      different quantities critical to the foraging cycle--visit rate (affected by g),
      probability of dancing (mpd and bpd), duration of dancing (mcirc), or probability
      of abandonment (A). We show that one parameter, A, affects nectar intake in a
      nonlinear way. Further, we show that colonies with a midrange value of any
      foraging parameter perform better than the average of colonies with high- and low
      range values, when profitable sources are available. Together these observations
      suggest that a heterogeneous colony, in which a range of parameter values are
      present, may perform better than a homogeneous colony. We modify the model to
      represent heterogeneous colonies and use it to show that the most important
      effect of heterogeneous foraging behaviour within the colony is to reduce the
      variance in the average quantity of nectar collected by heterogeneous colonies.

PMID- 12814602
TI  - In-phase implies large likelihood for independent codon model: distinguishing
      coding from non-coding sequences.
AB  - It is proven that under the independent codon model, the likelihood of a DNA
      coding sequence read according to the correct frame is asymptotically larger than
      that read with an incorrect frame. Based on this proposition, a single set of
      probabilities of the codon usage is enough for discriminating the six frames of
      coding sequences under the independent codon model. The direct coding sequence of
      Escherichia coli genome is taken as an example to examine the codon independency
      by using the mutual information and chi2 analysis. The contrast between the
      coding frame and the two offset frames is evident. A self-learning approach for
      generating training set is proposed to estimate probability parameters.

PMID- 12814603
TI  - Mutation load, functional overlap, and synthetic lethality in the evolution and
      treatment of cancer.
AB  - The efficacy of conventional anti-cancer drugs is puzzling in view of the
      ubiquitous tissue distribution and vital nature of their targets. Differences in
      cell cycling rates are not thought sufficient to explain chemotherapeutic
      selectivity. I suggest an alternative possibility based on the combinatorial
      effects of mutations in cancer cells. This model incorporates the concepts of
      synthetic-lethal interactions and mutation loads to explain the drug sensitivity
      of cancer cells. From this perspective, drugs that target complex processes that
      utilize genetically redundant or overlapping components, such as DNA replication
      and chromosome segregation, offer attractive target opportunities.

PMID- 12814604
TI  - Seed-cache exchange promotes coexistence and coupled consumer oscillations: a
      model of desert rodents as resource processors.
AB  - Most models of resource competition assume that coexistence of consumers depends
      on tradeoffs in their abilities to exploit shared resources along dimensions of
      environmental heterogeneity generated by factors external to the consumers.
      However, consumers may create heterogeneity themselves by modifying resources
      that they do not immediately consume; such "resource processing" is predicted to
      allow coexistence if consumers vary in use of resources in primary vs. modified
      form. To explore whether external food storage (caching) represents a form of
      resource processing that contributes to observed patterns of species coexistence,
      we developed a biologically explicit simulation model of competition for a well
      studied system, seed-eating desert heteromyid rodents. Here we present the model,
      compare competitive outcomes with and without inter-specific exchange of cached
      food, and describe population dynamics of coexisting competitors. The model
      predicts stable coexistence only when there is exchange of cached seeds via
      scavenging of caches left undefended by mortality or by pilferage of defended
      caches. Net interactions between coexisting consumers ranged from competition
      (10% of cases) to host-parasite (77%), commensalism (12%), and mutualism (1%).
      Population dynamics of coexisting consumers often showed strong periodicity and
      coupled synchronous or slightly lagged cycles, a possibility not previously
      anticipated for desert rodents occupying constant environments. Our model
      confirms that caching does represent a form of resource processing likely to play
      a significant role in the dynamics and diversity of communities of desert rodents
      and other caching animals.

PMID- 12814605
TI  - The effect of spatial scale of resistive inhomogeneity on defibrillation of
      cardiac tissue.
AB  - Defibrillation of cardiac tissue can be viewed in the context of dynamical
      systems theory as the attempt to move a dynamical system from the basin of
      attraction of one attractor (fibrillation) to another (the uniform rest state) by
      applying a stimulus whose form is physically constrained. Here we give an
      introduction to the physical mechanism of cardiac defibrillation from this
      dynamical perspective and examine the role of resistive inhomogeneity on
      defibrillation efficacy. Using numerical simulations with rotating waves on a one
      dimensional periodic ring, we study the role of the spatial scale of resistive
      inhomogeneity on defibrillation. For a rotating wave on a periodic ring there are
      three stable attractors, namely the uniform rest state, a wave traveling
      clockwise and a wave traveling counterclockwise. As a result, the application of
      a stimulus has the potential for three different outcomes, namely elimination of
      the wave, phase resetting of the wave, and reversal of the wave. The results
      presented here show that with resistive inhomogeneities of large spatial scale,
      all three of these transitions are possible with large amplitude shocks, so that
      the probability of defibrillation is bounded well below one, independent of
      stimulus amplitude. On the other hand, resistive inhomogeneities of small spatial
      scale produce a defibrillation threshold that is qualitatively consistent with
      that found experimentally, namely the probability of defibrillation success is an
      increasing function that approaches one for large enough stimulus amplitude.
      Extending these results to higher dimensions, we describe conditions for
      successful defibrillation of functional reentry with large scale spatial
      inhomogeneity, but find that elimination of anatomical reentry is quite
      difficult. With small spatial scale inhomogeneity, there are no similar
      restrictions.

PMID- 12814606
TI  - Allometric scaling law in a simple oxygen exchanging network: possible
      implications on the biological allometric scaling laws.
AB  - A simple model of an oxygen exchanging network is presented and studied. This
      network's task is to transfer a given oxygen rate from a source to an oxygen
      consuming system. It consists of a pipeline, that interconnects the oxygen
      consuming system and the reservoir and of a fluid, the active oxygen transporting
      element, moving through the pipeline. The network optimal design (total pipeline
      surface) and dynamics (volumetric flow of the oxygen transporting fluid), which
      minimize the energy rate expended in moving the fluid, are calculated in terms of
      the oxygen exchange rate, the pipeline length, and the pipeline cross-section.
      After the oxygen exchanging network is optimized, the energy converting system is
      shown to satisfy a 3/4-like allometric scaling law, based upon the assumption
      that its performance regime is scale invariant as well as on some feasible
      geometric scaling assumptions. Finally, the possible implications of this result
      on the allometric scaling properties observed elsewhere in living beings are
      discussed.

PMID- 12814607
TI  - Critical length of collagen fibrils in extracellular matrix.

PMID- 12814608
TI  - A comment on the protein folds as platonic forms.

PMID- 12814609
TI  - The total volume and the complete thickness of articular cartilage determined by
      MRI.

PMID- 12814610
TI  - Validation of cartilage volume and thickness measurements in the human shoulder
      with quantitative magnetic resonance imaging.
AB  - OBJECTIVE: To validate quantitative magnetic resonance imaging (qMRI) for the
      assessment of cartilage volume and thickness in thin and curved cartilage layers,
      such as the shoulder. METHODS: Eight shoulder specimens from healthy individuals
      (aged 31-69 years) were investigated using a 3D gradient echo sequence with
      selective water excitation. After segmentation with a B-spline Snake algorithm,
      the cartilage volume and thickness were determined three dimensionally. The
      cartilage volume data were compared with water displacement of surgically removed
      tissue, and the thickness with A-mode ultrasound. RESULTS: The glenoid and
      humeral head cartilage volume from qMRI agreed highly with that from water
      displacement (systematic difference, +/-1 to +/-3%; absolute difference, 4 to
      7%). For the cartilage thickness, the mean systematic difference ranged from -17%
      (mean cartilage thickness of the glenoid) to +7% (maximal cartilage thickness of
      the glenoid); the standard error of the estimate was 3.7% for the humeral head,
      and 6.4% for the glenoid. CONCLUSIONS: The applied technique can be used for
      accurate determination of cartilage volume and thickness in human joints with
      highly curved and thin cartilage layers, such as the shoulder. In vivo
      application of this method will depend on the development of efficient surface
      coils that allow high resolution imaging under in situ conditions.

PMID- 12814611
TI  - Measurement accuracy of focal cartilage defects from MRI and correlation of MRI
      graded lesions with histology: a preliminary study.
AB  - OBJECTIVES: Although accurate spatial measurement of cartilage thickness from MRI
      is possible, no studies have assessed the accuracy of measuring cartilage defect
      dimensions from MRI. In addition, current MR grading scales for assessing
      cartilage lesions have limited categories, and little is known about how well
      these scales correlate with histological assessment of the lesion. The objective
      of this preliminary study is to address both these issues. METHODS: We performed
      two experiments on four cadaver knee joints from elderly donors: Experiment 1
      assessed the accuracy of measuring controlled defects in cartilage, and
      Experiment 2 compared MRI grading (Noyes scale) of natural cartilage lesions to
      histological grading (Mankin scale) of the sectioned cartilage tissue. MRI was
      performed on 1.5 T clinical scanner (fat-suppressed 3D-SPGR at
      TR/TE/alpha=55/13.5/45 and 256 x 256 matrix). RESULTS: The mean difference
      between defect diameters measured and introduced was less than 0.1mm, which was
      statistically insignificant (P=0.754). Defect depth was less accurate at >0.4mm,
      significantly under predicting actual defect depth (P=0.004). Correlation between
      Noyes grading scores and Mankin grading scores of natural lesions was moderately
      high (r=0.7) and statistically significant (P=0.001). CONCLUSIONS: Three
      dimensional mapping of cartilage thickness shows great promise for the accurate
      measurement of focal cartilage defects, though improvement is needed. The Noyes
      grading scale is consistent with histological Mankin grading of cartilage
      lesions, though enhancement of MR grading scales is needed, and warranted, based
      on the signal intensity information available from clinical MRI. Integration of
      these two analyses-focal defect measurement and signal intensity analysis-could
      potentially result in a valuable clinical tool for early osteoarthritis diagnosis
      and longitudinal tracking.

PMID- 12814612
TI  - Distribution of MR-detected cartilage defects of the patellofemoral joint in
      chronic knee pain.
AB  - OBJECTIVES: The aim of the study was to detect cartilage defects and determine
      the center of these defects in MR imaging of the patellofemoral joint (PFJ) in
      middle-aged people with chronic knee pain. DESIGN: In the format of a prospective
      study of early osteoarthritis (OA), this cross-sectional study of the signal knee
      (the most painful one at inclusion in the study in 1990) in 59 individuals, 30
      women and 29 men (aged 41-58 years, mean 50 years) with chronic knee pain, with
      or without radiographically determined knee OA, was examined using MR imaging on
      a 1.0 T imager. Cartilage defects and the center of these defects in the PFJ were
      recorded. RESULTS: Cartilage defects were found more often in the patella (40
      knees) than in the femoral trochlea (23 knees) (P<0.001) and were unevenly
      distributed in the patella (P<0.001), with most cartilage defects in the mid
      patella. CONCLUSIONS: Since cartilage defects occur more commonly in the mid
      patella, radiographs obtained with a knee flexion of approximately 45 degrees may
      be more accurate to show cartilage defects of early OA of the PFJ than views with
      another knee flexion.

PMID- 12814613
TI  - Response relationship of VAS and Likert scales in osteoarthritis efficacy
      measurement.
AB  - OBJECTIVE/BACKGROUND: Efficacy in osteoarthritis (OA) is principally measured
      using subjective visual analogue (VAS) and/or Likert scale responses. The
      relationship between these two scales and their relative precision in
      discriminating active from placebo treatment in OA patients was determined.
      DESIGN/METHODS: Patient overall pain assessment, and patient and investigator
      global assessments were each measured on a 100mm VAS and on a 0 to 4 point Likert
      scale in a 6-week OA study of rofecoxib vs placebo. The relationship between the
      VAS and Likert responses was examined graphically and via summary statistics.
      Analysis of variance was used to assess consistency of the VAS/Likert
      relationship over time and across the different endpoints. Precision was compared
      using effect size, and normality of VAS scale of measurement was assessed using
      the Shapiro-Wilk test. RESULTS: Mean VAS scores and changes from baseline at
      individual time points were generally highly correlated with corresponding Likert
      responses (r-values generally approximately 0.7-0.8). The magnitude of VAS values
      and changes varied depending on endpoint, on the associated magnitude of
      increment of Likert score, and on the Likert baseline value (i.e., where on the
      Likert scale the change was occurring). Precision of VAS and Likert responses to
      detect difference between treatments was generally similar with effect sizes
      approximately 1. Normality and homogeneity of variance of VAS scores was most
      closely approximated by actual changes in comparison to percent change or log
      transformed measures. CONCLUSIONS: VAS and Likert responses are highly correlated
      and yield similar precision for discriminating treatments in OA patients. Since
      Likert responses are easier to administer and interpret, they may be preferable
      to measure OA response.

PMID- 12814614
TI  - Early osteoarthritic changes of human femoral head cartilage subsequent to femoro
      acetabular impingement.
AB  - OBJECTIVE: To use the surgical samples of patients with femoro-acetabular
      impingement due to a nonspherical head to analyze tissue morphology and early
      cartilage changes in a mechanical model of hip osteoarthritis (OA). DESIGN: An
      aberrant nonspherical shape of the femoral head has been assumed to cause an
      abutment conflict (impingement mechanism) of the hip with subsequent cartilage
      lesions of the acetabular rim and surface alterations of the nonspherical portion
      of the head. In this study, 22 samples of the nonspherical portions of the head
      have been obtained during hip surgery from young adults (mean 30.4 years, range
      19-45 years) with an impingement conflict. The samples were first compared with
      tissue from the same area obtained from six age-matched deceased persons (control
      group) with normal hip morphology and second with cartilage from 14 older
      patients with advanced OA. All samples were characterized histologically and
      hyaline cartilage was graded according to the Mankin criteria. They were further
      subjected to examination on a molecular basis by immunohistology for cartilage
      oligomeric matrix protein (COMP), tenascin-C and a collagenase cleavage product
      (COL2-3/4C(long)) and by in situ hybridization for collagen type I and collagen
      type II. RESULTS: All samples from the patient group revealed hyaline cartilage
      with degenerative signs. According to the Mankin criteria, the cartilage
      alterations were significantly different when compared with the control group
      (p=0.007) but were less distinct when compared with cartilage from patients with
      advanced OA (p=0.014). Positive staining and distribution pattern for COMP,
      tenascin-C and COL2-3/4C(long) showed similarities between the samples from the
      impingement group and osteoarthritic cartilage but they were distinctly different
      when compared with healthy cartilage. Levels of collagen I and II transcripts
      were upregulated in 6 and 10, respectively, of the 14 samples with OA and in 9
      and 12, respectively, of the 22 samples from the impingement group. None of the
      samples from the control group showed upregulation of Collagen I and II mRNA.
      CONCLUSIONS: The aberrant nonspherical portion of the femoral head in young
      patients with an impingement conflict consists of hyaline cartilage which shows
      clear degenerative signs similar to the findings in osteoarthritic cartilage. The
      tissue alterations are distinctly different when compared with a control group,
      which substantiates an impingement conflict as an early mechanism for
      degeneration at the hip joint periphery.

PMID- 12814615
TI  - Linking osteoarthritis-specific health-status measures to the International
      Classification of Functioning, Disability, and Health (ICF).
AB  - OBJECTIVES: The objective of this study was to link the Western Ontario and
      McMaster Universities (WOMAC) and Lequesne-Algofunctional indices to the ICF on
      the basis of linking rules developed specifically to accomplish this aim. The
      linking process enables the understanding of the relationship between health
      status measures and the ICF. METHODS: Since the fifth World Health
      Organisation/International Liege Against Rheumatism (WHO/ILAR) Task Force and the
      Outcome Measures in Rheumatology Clinical Trials (OMERACT) group recommend the
      use of WOMAC and the Lequesne-Algofunctional indices in patients with
      osteoarthritis of the hip and knee in clinical trials, these two health-status
      measures have been used in this study. Both health-status measures were linked to
      the ICF separately by two trained health professionals. Consensus between health
      professionals was used to decide which ICF category should be linked to each
      item/concept of the two questionnaires. To resolve disagreements between the two
      health professionals, a third person trained in the linking rules was consulted.
      RESULTS: Except for the concept of 'morning stiffness', both health professionals
      agreed on the ICF category chosen to link all the items/concepts of both
      questionnaires. Altogether, 29 different ICF categories have been linked. Five
      ICF categories belong to the ICF component 'body functions', 23 categories to the
      component 'activities and participation', and one category to 'environmental
      factors'. Both questionnaires have 10 ICF categories in common. CONCLUSIONS: The
      results of the linking process reflect both the structure of the two
      questionnaires studied and the relationship between them, showing that the ICF
      classification can become the cardinal reference for existing health-status
      measures.

PMID- 12814616
TI  - Identification and differential expression of human collagenase-3 mRNA species
      derived from internal deletion, alternative splicing, and different
      polyadenylation and transcription initiation sites.
AB  - OBJECTIVE: Collagenase-3 is a metalloprotease that plays a role in tissue
      remodeling and pathological processes including arthritis. The human gene is
      transcribed into major (3.0 and 2.5 kb) and minor (2.2/2.0 kb) transcripts, as
      seen in Northern blot assays. We investigated the possibility that other
      transcripts, not detectable by Northern blot, were synthesized as either coding
      or regulatory RNAs that would modulate collagenase-3 expression and
      function/activity. DESIGN: We screened a cDNA library and total RNA from human
      chondrocytes by plaque hybridization and RT-PCR, and expressed the transcripts in
      a cellular environment. The levels of expression of each transcript in normal and
      osteoarthritic joint cells and cartilage were monitored by RT-PCR. RESULTS: We
      identified five different collagenase-3 RNA species derived from alternative
      polyadenylation sites (COL3-APS), internal deletion (COL3-DEL), alternative
      splicing (COL3-9B/COL3-9B-2), and different transcription initiation site (COL3
      ATS and COL3-ATS-INT). Each transcript could be translated in a cellular
      environment. Interestingly, the proteins translated from the COL3-DEL and COL3-9B
      2 transcripts had a modified hemopexin-like domain, suggesting altered
      collagenolytic activities. The transcript types COL3-APS, COL3-9B-2, and COL3-ATS
      were up-regulated in the osteoarthritic samples and expressed in the
      chondrosarcoma cell line SW1353. CONCLUSION: Our data show that the human
      collagenase-3 gene is subjected to different levels of regulation and constitutes
      a more complex system than was originally thought.

PMID- 12814617
TI  - Comparison of the catabolic effects of fibronectin fragments in human knee and
      ankle cartilages.
AB  - OBJECTIVE: To compare the response of knee and ankle cartilages to fibronectin
      fragments (Fn-f) in terms of kinetics of matrix proteoglycan (PG) degradation and
      synthesis, since previous data had shown that knee was more sensitive to Fn-f in
      terms of steady-state PG content. DESIGN: Human knee and ankle cartilage explants
      were treated with the 29kDa Fn-f, and its effects on PG-degradation kinetics, on
      the half-lives of 35S-sulfate-labeled PG, on PG synthesis suppression and on
      matrix metalloproteinase -3 (MMP-3) were compared. Cultures were also treated
      with the interleukin (IL) receptor antagonist protein (IRAP) in order to
      determine whether IL-1 is involved in the Fn-f effect. RESULTS: The Fn-f enhanced
      PG-degradation rates in both human knee and ankle cartilages. Knee cartilage
      showed a greater effect of Fn-f on half-lives of newly synthesized 35S-labeled PG
      than ankle. The extent of release of MMP-3 was similar for human ankle and knee
      cartilages. However, PG synthesis in knee cartilage was sensitive to 10- to 100
      fold lower concentrations of Fn-f than was ankle cartilage. IRAP partially
      reversed Fn-f activity in ankle cartilages. CONCLUSIONS: The role of Fn-f in
      proteolysis leading to cartilage damage appears to be minor in human cartilages
      than had previously been shown for bovine. This decreased proteolysis is true for
      both knee and ankle. The major difference between human ankle and knee cartilage
      appears to be greater sensitivity to PG synthesis suppression in knee cartilage.
      A further indication that IL-1 is involved in the pathway was provided by the
      partial reversal with IRAP.

PMID- 12814619
TI  - Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity.
AB  - Glutamate-cysteine ligase (GCL; also known as gamma-glutamylcysteine synthetase)
      is the rate-limiting enzyme in glutathione (GSH) synthesis. Traditional assays
      for the activity of this enzyme are based either on coupled reactions with other
      enzymes or on high-performance liquid chromatography (HPLC) assessment of gamma
      glutamylcysteine (gamma-GC) product formation. We took advantage of the reaction
      of naphthalene dicarboxaldehyde (NDA) with GSH or gamma-GC to form cyclized
      products that are highly fluorescent. Hepa-1 cells which were designed to
      overexpress mouse GCL and mouse liver homogenates were used to evaluate and
      compare the utility of the NDA method with an assay based on monobromobimane
      derivatization and HPLC analysis with fluorescence detection. Excellent agreement
      was found between GCL activities measured by HPLC and NDA-microtiter plate
      analyses. This assay should be useful for high-throughput GCL activity analyses.

PMID- 12814620
TI  - Microplate live cell assay system for early events in mechanotransduction.
AB  - For studying mechanotransduction in cultured cells, we developed a microplate
      assay using a fluorescence/luminescence plate reader equipped with software
      controlled injectors to deliver a reproducible mechanical stimulus (adjustable
      for both timing and force) and immediately measure adenosine 5(')-triphosphate
      (ATP) release and calcium mobilization. Suspension or adherent chondrocyte
      cultures in 96-well plates were incubated with firefly luciferase and luciferin
      for the ATP assay or loaded with Fluo-3-acetoxy methylester for intracellular
      calcium measurement. Steady state ATP release was measured in resting cells; then
      mechanical stimulation was delivered by injection of an equal volume of buffer
      into the wells. Serial integrations of 20 to 500ms allowed real-time analysis of
      the time course of ATP release. Luminescence increased within 500ms indicating
      the rapidity of ATP release in chondrocyte mechanotransduction. Subsequent
      injection of a cell lysis solution allowed quantitation of total cellular ATP as
      an internal control of cell viability and number. Intracellular calcium was also
      elevated within 500ms of fluid injection. This assay is easily adapted for
      changes in intracellular pH or other ions by use of different commercially
      available fluorescent indicators. The live-cell assay using fluid injection as a
      mechanical stimulus is a valuable tool for dissecting the role of signaling
      pathways in mechanotransduction.

PMID- 12814621
TI  - Quantification of acetaminophen by oxidation with tyrosinase in the presence of
      Besthorn's hydrazone.
AB  - A method for the quantitative determination of acetaminophen by measuring the
      kinetics of its oxidation by the enzyme tyrosinase in the presence of the
      nucleophilic agent 3-methyl-2-benzothiazolone hydrazone (Besthorn's hydrazone) is
      described. The hydrazone traps the o-quinone product of the catalytic activity, 4
      acetamido-o-benzoquinone, thus increasing the level of the catecholic
      intermediate, 3'-hydroxyacetaminophen, in the pathway, as was shown by liquid
      chromatography. This reduces the time necessary for the steady state to be
      reached and increases the steady state oxidation rate, reaching activations of
      124 times at an initial concentration of 3mM hydrazone. Despite being rapid and
      simple the method is thorough and provides a linear range of quantification of
      the drug from 10 nmol/ml to 1.4 micromol/ml. The assay can be performed in
      continuous or discontinuous form, meaning that it can be used with the
      immobilized enzyme for the design of specific biosensors.

PMID- 12814622
TI  - Thermostable continuous coupled assay for measuring glucose using glucokinase and
      glucose-6-phosphate dehydrogenase from the marine hyperthermophile Thermotoga
      maritima.
AB  - A novel, thermostable adaptation of the coupled-enzyme assay for monitoring
      glucose concentrations was developed for an optimal temperature of 85 degrees C.
      This is the first report of a thermostable glucostat from a marine
      hyperthermophile. The continuous assay, using glucokinase (Glk) and glucose-6
      phosphate dehydrogenase (Gpd) from Thermotoga maritima, demonstrated robust
      activity over a range of temperatures (75-90 degrees C) and pH values (6.8- 8.5).
      Purified glucokinase had a monomeric molecular mass of 33.8kDa while that of
      glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate:NADP oxidoreductase) was
      57.5kDa. The high-temperature assay provided a method for directly assaying the
      activity of another hyperthermophilic enzyme, 1,4-beta-D-glucan glucohydrolase
      (GghA) from Thermotoga neapolitana. To provide a benchmark for protein
      engineering experiments involving GghA, a three-enzyme continuous assay
      (performed at 85 degrees C), linking wild-type GghA, Glk, and Gpd, measured
      glucose produced from GghA's hydrolysis of cellobiose, one of GghA's secondary
      substrates. The assay established the kinetic behavior of wild-type GghA toward
      cellobiose and was used to screen for changes in the catalytic efficiency of
      variant GghA(s) induced by random mutagenesis. The assay's development will allow
      high-throughput screening of other thermostable glucose-producing enzymes,
      including those applicable to commercial biomass conversion.

PMID- 12814623
TI  - High-performance liquid chromatography method to analyze free and total urinary
      pyridinoline and deoxypyridinoline.
AB  - The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are
      established markers of bone resorption measured in blood and urine and are used
      to investigate bone metabolism and manage bone diseases. Unfortunately, the
      currently observed interlaboratory variability caused by inconsistent assay
      calibration limits the optimal use of these markers. A high-performance liquid
      chromatography (HPLC)-based assay was developed using synthetic PYD and DPD as
      calibrators to analyze free and total PYD and DPD in urine. The spectroscopic
      characteristics of the synthetic calibrators were identical to those of
      calibrators isolated from bone. The mean intraassay variabilities of the HPLC
      method were 4.1 and 3.8%, respectively, for total DPD and PYD and 9.8 and 9.5%,
      respectively, for free DPD and PYD. The mean interassay variabilities were 9.1
      and 8.2% for total DPD and PYD and 8.6 and 7.0% for free DPD and PYD,
      respectively. The mean recoveries were 98.1% for total DPD, 100.8% for total PYD,
      98.6% for free DPD, and 94.9% for free PYD. The method exhibits a good
      correlation with a commercial immunoassay and with other HPLC assays currently
      used in hospital laboratories.

PMID- 12814624
TI  - Atmospheric pressure chemical ionization-mass spectrometry method to improve the
      determination of dansylated polyamines.
AB  - Determination of polyamine pools is still a step impossible to circumvent in
      studies aimed at determining the pathophysiological role of natural polyamines.
      In addition, polyamine measurement in biological fluids and tissues may have
      clinical relevance, especially in cancer patients. Among the wide panel of
      analytical methods developed for the quantification of polyamines, high
      performance liquid chromatographic (HPLC) separation of polyamines after
      derivatization with dansyl chloride remains the most commonly used method. In
      this work, we show that atmospheric pressure chemical ionization-mass
      spectrometry (MS) can be used to detect and quantify biologically relevant
      polyamines after dansylation, without chromatographic separation. Positive-ion
      mass spectra for each dansylated polyamine were generated after optimization by
      flow injection analysis (FIA). FIA coupled with MS detection by selected ion
      monitoring greatly increased the sensitivity of the polyamine detection. The
      method is linear over a wide range of polyamine concentrations and allows
      detection of quantities as low as 5 fmol. The FIA/MS method is about 50-fold more
      sensitive than the conventional HPLC/fluorimetry procedure. A good correlation
      (r>0.98) between these two methods was observed. The FIA/MS method notably
      reduces the time of analysis per sample to 1.5 min and turns out to be rapid,
      efficient, cost saving, reproducible, and sufficiently simple to allow its
      routine application.

PMID- 12814625
TI  - Rapid detection of apoptosis through real-time reverse transcriptase polymerase
      chain reaction measurement of the small cytoplasmic RNA Y1.
AB  - Apoptosis could be measured in mammalian cells by measuring the degradation of
      the small cytoplasmic human RNA Y1 (hY1) by real-time quantitative fluorescent
      reverse transcriptase polymerase chain reaction (RT-PCR). In FAS-antibody-treated
      Jurkat T cell leukemia cells degradation of hY1 occurred rapidly and was complete
      at about 6h. As in apoptotic Jurkat cells, protein synthesis is arrested only
      after about 12h; this implies that protein synthesis can occur without scRNA-Y1.
      The degradation of hY1 could be blocked with peptide-based inhibitors of caspase
      8 and with lower efficacy with caspases 1 and 3 and with ZnSO4. No effects were
      observed after inhibition of caspases 2, 6, and 9. Degradation of hY1 could also
      be demonstrated after treatment of A549 lung carcinoma cells treated with
      Staurosporin, Paclitaxel, or the histone deacetylase inhibitor LAQ824. RT-PCR
      systems based on SYBR Green, Amplifluor Uniprimer, or 5' nuclease Taqman could be
      used with increasing sensitivity. This apoptosis assay requires quantities of
      total cell RNA equivalent to only a few tissue culture cells and is especially
      suited to measure apoptosis in projects where RNA samples are already available
      from gene expression studies.

PMID- 12814626
TI  - Stability analysis for long-term storage of naked DNA: impact on nonviral in vivo
      gene transfer.
AB  - The transfer of naked DNA is gaining growing acceptance for nonviral gene
      therapy. Integrity and stability of the DNA used in nonviral gene therapy is
      known to be decisive for efficacy of gene transfer and transgene expression.
      Thus, preclinical and clinical studies require the safe storage of DNA
      preparations to ensure defined quality and conformation. To evaluate the
      influence of potentially destructive processes on plasmid DNA associated with
      long-term storage, capillary gel electrophoresis (CGE) analysis of the LacZ
      expressing pCMVbeta plasmid over a period of 13 months was performed. The CGE
      analysis revealed that stable storage conditions at -80 degrees C prevent an
      increase in open circular (oc) plasmid, preserving the covalently closed circular
      (ccc) form, which is sought for efficient gene transfer. By contrast, long-term
      storage of plasmid DNA at 4 degrees C leads to the rapid decline of the ccc form
      and the increase of oc and linear DNA molecules. The use of naked DNA stored for
      1, 2, or 13 months at -80 degrees C showed similar in vivo transfer efficiencies
      by jet-injection. Therefore, analysis of plasmids by CGE allows the reliable
      determination of integrity and distribution of the topology of the DNA by
      quantitative means.

PMID- 12814627
TI  - Multianalyte immunoassay with self-assembled addressable microparticle array on a
      chip.
AB  - This paper describes the random fluidic self-assembly of metallic particles into
      addressable two-dimensional microarrays and the use of these arrays as a platform
      for constructing a biochip useful for bioassays. The basic units in the assembly
      were the microfabricated particles carrying a straightforward visible code and
      the corresponding array template patterned on a glass substrate. The particles
      consisted of a hydrophobic and magnetic Ni-polytetrafluoroethylene (PTFE)
      composite layer on one face, and on the other face a gold layer that was modified
      for biomolecular attachment. An array template was photoresist-patterned with
      spatially discrete microwells in which an electrodeposited Ni-PTFE hydrophobic
      composite layer and a hydrophobic photo-adhesive coating were deposited. The
      particles, after biomaterial attachment and binding processes in bulk, were self
      assembled randomly onto the lubricated bonding sites on the chip substrate,
      driven by a combination of magnetic, hydrophobic, and capillary interactions. The
      encoding symbol carried by the particles was used as the signature for the
      identification of each target/assay attached to the particle surface. We
      demonstrate here the utility of microfabricated-encoded particle arrays for
      conducting multianalyte immunoassays in a parallel fashion with the use of
      imaging detection.

PMID- 12814628
TI  - In vitro measurement of nuclear permeability changes in apoptosis.
AB  - In the eukaryotic cell, exchange of biomolecules between nucleus and cytoplasm is
      a highly regulated process which responds sensitively to changes of the
      environment. One well-known cellular response to environmental challenges is cell
      death by apoptosis. In fact, apoptosis has been shown to affect the
      nucleocytoplasmic transport machinery, in particular the nuclear pore, by
      modulating its size exclusion limit for passive diffusion. The underlying
      molecular factors are still unknown, mainly because of the lack of a suitable
      system to detect and quantitate the apoptotic effects on the nuclear pore. Here
      we present an assay that was designed to measure alterations of the permeability
      of the nuclear envelope under apoptotic conditions. The assay is based on the
      well-established technique of selective permeabilization of the plasma membrane
      with digitonin and allows assessment of permeability changes in nonfixed samples.
      It comprises a computer program, called Nuclear Permeability Assay, for the
      quantitation of the nuclear fluorescence signal, which may be generally employed
      for the evaluation of in vitro transport systems using semipermeabilized cells,
      such as assays for nuclear import and export.

PMID- 12814629
TI  - Stability of diacylglycerol acyltransferase in dehydrated bovine muscle tissue.
AB  - Meaningful estimates of diacylglycerol acyltransferase (EC 2.3.1.20) activity in
      different tissue samples require effective, unbiased methods of sample storage.
      Samples of the pars costalis diaphragmatis muscle (skirt muscle of the diaphragm)
      were obtained from 18- to 20-month-old cattle and assayed for microsomal protein
      content and diacylglycerol acyltransferase activity after having been stored
      under various conditions as dissected tissue or microsomes prepared from
      dissected tissue. There was relative enrichment of diacylglycerol acyltransferase
      specific activity (p<0.05) when samples prepared from the pars costalis
      diaphragmatis muscle were dehydrated and stored for 2 weeks, as compared to the
      control condition (in which the microsome fraction was prepared from fresh pars
      costalis diaphragmatis muscle and assayed immediately). The results suggested
      that dehydration was an effective method of storage for bovine muscle samples
      destined for estimation of the microsomal diacylglycerol acyltransferase
      activity. The dehydration approach for preparing samples for analysis of
      diacylglycerol acyltransferase activity might also prove useful to investigators
      who are interested in obtaining reliable estimates of the activity of other
      enzymes in tissue samples.

PMID- 12814630
TI  - Reconstituted 3-dimensional human skin of various ethnic origins as an in vitro
      model for studies of pigmentation.
AB  - Reconstituted 3-dimensional human skin equivalents containing melanocytes and
      keratinocytes on an artificial dermal substitute are gaining popularity for
      studies of skin metabolism because they exhibit morphological and growth
      characteristics similar to human epidermis. In this study, we show that such a
      pigmented epidermis model can be used to assess the regulation of pigmentation by
      known melanogenic compounds. In monolayers or in melanocyte-keratinocyte co
      cultures, melanocyte-keratinocyte interactions are missing or are spatially
      limited. The commercial skin equivalents used in this study were derived from
      epidermal cells obtained from donors of three different ethnic origins (African-
      American, Asian, and Caucasian), and they reflect those distinct skin phenotypes.
      We used these pigmented human epidermis models to test compounds for potential
      effects on pigmentation in a more physiologically relevant context, which allows
      further characterization and validation of interesting melanogenic factors. We
      used known melanogenic stimulators (alpha-melanocyte-stimulating hormone and 3,4
      dihydroxyphenylalanine) and inhibitors (hydroquinone, arbutin, kojic acid, and
      niacinamide) and examined their effects on the production of melanin and its
      distribution in upper layers of the skin. Our studies indicate that commercial
      skin equivalents provide a convenient and cost-effective alternative to animal
      testing for evaluating the regulation of mammalian pigmentation by melanogenic
      factors and for elucidating their mechanisms of action.

PMID- 12814631
TI  - A high-throughput-compatible assay for determining the activity of fatty acid
      amide hydrolase.
AB  - Fatty acid amide hydrolase (EC 3.5.1.4.) is the enzyme responsible for the rapid
      degradation of lipid-derived chemical messengers such as anandamide, oleamide,
      and 2-arachidonoylglycerol. The pharmacological characterization of this enzyme
      in vivo has been hampered by the lack of selective and bioavailable inhibitors.
      We have developed a simple, radioactive, high-throughput-compatible assay for
      this enzyme based on the differential absorption of the substrate and its
      products to activated charcoal. The assay was validated using known inhibitors.
      It may be applied for the identification of new inhibitors from a compound
      library.

PMID- 12814632
TI  - Microtiter plate cellular assay for human steroid sulfatase with fluorescence
      readout.
AB  - Steroid sulfatase (STS; E.C. 3.1.6.2) is an enzyme involved in the local
      production of estrogens and androgens in target organs. Inhibitors of steroid
      sulfatase activity are considered novel therapeutic agents for the treatment of
      different pathologic conditions, including cancers of breast, endometrium, and
      prostate and disorders of the pilosebaceous unit. Evaluation of steroid sulfatase
      inhibition in cells up to now has been a cumbersome process, involving the
      extraction of a radioactive cleavage product into organic solvents. Here, we
      describe a rapid, nonradioactive cellular assay in microtiter plate format, using
      4-methylumbelliferyl sulfate as a substrate. The reaction product, 4
      methylumbelliferone, is read in a fluorescence microtiter plate reader. Several
      cell lines were assayed for sulfatase activity. To increase the sensitivity of
      the assay, we developed a Chinese hamster ovary (CHO) cell line stably
      transfected with a cDNA encoding the human steroid sulfatase. The steroid
      sulfatase activity in transfected cells correlated with the presence of the
      enzyme in these cells, as determined by immunofluorescence. For most STS
      inhibitors tested, including estrone-3-O-sulfamate, the results from the CHO
      cellular assay were in good agreement with those from a standard cell-free assay.

PMID- 12814633
TI  - A novel sensitive high-performance liquid chromatography/electrochemical
      procedure for measuring formaldehyde produced from oxidative deamination of
      methylamine and in biological samples.
AB  - Formaldehyde is a well-known environmental toxic hazard. It is also a product of
      oxidative deamination of methylamine catalyzed by semicarbazide-sensitive amine
      oxidase (SSAO). Increased SSAO-mediated deamination has been implicated in some
      pathophysiological conditions, such as diabetic complications. The measurement of
      formaldehyde in the enzymatic reactions and in vivo production using conventional
      methods was not straightforward due to limitations of selectivity and
      sensitivity. A novel high-performance liquid chromatography
      (HPLC)/electrochemical procedure for the measurement of formaldehyde has been
      developed. The measurement is based on the formation of adducts between
      formaldehyde and dopamine. These adducts can be selectively purified and
      concentrated using a batch method of alumina absorption, separated by HPLC, and
      electrochemically quantified. The method is highly selective and substantially
      more sensitive, i.e., detection of picomole levels of formaldehyde, than the
      conventional methods. The procedure not only facilitates the assessment of SSAO
      activity in vitro but also is useful for assessing formaldehyde in tissues and
      biological fluids.

PMID- 12814634
TI  - Charge equilibria and pK(a) of malvidin-3-glucoside by electrophoresis.
AB  - Paper electrophoresis has been used over the pH range 1.2 to 10.4 to measure
      apparent pK(a) values for malvidin-3-O-glucoside of pK(a(1)) 1.76+/-0.07,
      pK(a(2)) 5.36+/-0.04, and pK(a(3)) 8.39+/-0.07. Using solvent partitioning
      between buffered aqueous solutions and n-octanol, several micro-pK(a) constants
      for malvidin-3-O-glucoside were also identified, highlighting the complex nature
      of malvidin-3-glucoside equilibria. As a nonspectrophotometric procedure, the
      charge-dependent electrophoretic mobility method provided independent information
      on the net charge and color of anthocyanin species at wine pH (ca. 3.6). At this
      pH, the color of malvidin-3-glucoside in red wines is consistent only with the
      uncharged quinonoidal base as a major colored component of the equilibria.

PMID- 12814635
TI  - Resolving near-ultraviolet circular dichroism spectra of single trp mutants in
      tear lipocalin.
AB  - Near-ultraviolet circular dichroism (near-UV CD) spectra of tryptophan residues
      in proteins are complicated because the line shapes are derived from the overlap
      of both the 1L(a) and the 1L(b) electronic bands that vary independently.
      Contributing to this complexity, tryptophan near-UV CD spectra differ in the
      relative amplitude of the 0-0 vibronic band compared to the rest of the 1L(b)
      spectrum, an inherent feature that may result in poor fitting. To resolve this
      problem, a computer program that incorporated the separation of the 0-0
      transition of 1L(b) component from the rest of the 1L(b) was written in LabVIEW
      and its amplitude was allowed to vary independently. This method showed
      dramatically improved fitting of 1L(a) and 1L(b) components in the near-UV CD
      tryptophan spectra in tear lipocalin mutants featuring low intensity of the 0-0
      1L(b) component. Side chain dynamic characteristics (mobility and accessibility
      to the solvent) identified from different spectroscopic techniques were related
      to differences in Trp near-UV CD spectra. This method is broadly applicable to
      different types of Trp near-UV CD spectra.

PMID- 12814636
TI  - Ligation-based synthesis of oligonucleotides with block structure.
AB  - We describe here a method for the synthesis of oligonucleotides with block
      structure (padlock probes, primers for multiplex polymerase chain reaction (PCR),
      and ligation-independent cloning), based on the ligation of presynthesized parts
      by T4 DNA ligase. The advantages of this approach are: (i) suitability of the
      technology for any producer-from synthesis company to laboratory, (ii) high
      quality and adjustable scale of synthesis, and (iii) possibility of including any
      modified bases inexpensively in the common part of the oligonucleotide. Clear
      difference of sizes of products and substrates makes the synthesis amenable to
      automation. For large series of padlock probes, the price per one primer
      approaches the price of the locus-specific parts. We demonstrate the application
      of this method to two different tasks: preparative-scale production of padlock
      probes and small-scale synthesis of PCR primers.

PMID- 12814637
TI  - Analysis of DNA extraction buffer components from plant tissue by polymerase
      chain reaction.

PMID- 12814638
TI  - Quick, simple, and sensitive RNA quantitation.

PMID- 12814640
TI  - Reductive dehalogenation of monobromobimane by tris(2-carboxyethyl)phosphine.

PMID- 12814639
TI  - Analysis of gluconeogenic pathways in vivo by distribution of 2H in plasma
      glucose: comparison of nuclear magnetic resonance and mass spectrometry.

PMID- 12814641
TI  - The chemical biology of branched-chain lipid metabolism.
AB  - Mammalian metabolism of some lipids including 3-methyl and 2-methyl branched
      chain fatty acids occurs within peroxisomes. Such lipids, including phytanic and
      pristanic acids, are commonly found within the human diet and may be derived from
      chlorophyll in plant extracts. Due to the presence of a methyl group at its beta
      carbon, the well-characterised beta-oxidation pathway cannot degrade phytanic
      acid. Instead its alpha-methylene group is oxidatively excised to give pristanic
      acid, which can be metabolised by the beta-oxidation pathway. Many defects in the
      alpha-oxidation pathway result in an accumulation of phytanic acid, leading to
      neurological distress, deterioration of vision, deafness, loss of coordination
      and eventual death. Details of the alpha-oxidation pathway have only recently
      been elucidated, and considerable progress has been made in understanding the
      detailed enzymology of one of the oxidative steps within this pathway. This
      review summarises these recent advances and considers the roles and likely
      mechanisms of the enzymes within the alpha-oxidation pathway.

PMID- 12814642
TI  - Comparison of the properties of prostaglandin H synthase-1 and -2.
AB  - Biosynthesis of prostanoid lipid signaling agents from arachidonic acid begins
      with prostaglandin H synthase (PGHS), a hemoprotein in the myeloperoxidase
      family. Vertebrates from humans to fish have two principal isoforms of PGHS,
      termed PGHS-1 and-2. These two isoforms are structurally quite similar, but they
      have very different pathophysiological roles and are regulated very differently
      at the level of catalysis. The focus of this review is on the structural and
      biochemical distinctions between PGHS-1 and-2, and how these differences relate
      to the functional divergence between the two isoforms.

PMID- 12814643
TI  - The role of vitamin E in atherosclerosis.
AB  - Epidemiological and biochemical studies infer that oxidative processes, including
      the oxidation of low-density lipoprotein (LDL), are involved in atherosclerosis.
      Vitamin E has been the focus of several large supplemental studies of
      cardiovascular disease, yet its potential to attenuate or even prevent
      atherosclerosis has not been realised. The scientific rationale for vitamin E
      supplements protecting against atherosclerosis is based primarily on the
      oxidation theory of atherosclerosis, the assumption that vitamin E becomes
      depleted as disease progresses, and the expectation that vitamin E prevents the
      oxidation of LDL in vivo and atherogenic events linked to such oxidation.
      However, it is increasingly clear that the balance between vitamin E and other
      antioxidants may be crucial for in vivo antioxidant protection, that vitamin E is
      only minimally oxidised and not deficient in atherosclerotic lesions, and that
      vitamin E is not effective against two-electron oxidants that are increasingly
      implicated in both early and later stages of the disease. It also remains unclear
      as to whether oxidation plays a bystander or a casual role in atherosclerosis.
      This lack of knowledge may explain the ambivalence of vitamin E and other
      antioxidant supplementation in atherosclerosis.

PMID- 12814644
TI  - Exposure of platelet membrane phosphatidylserine regulates blood coagulation.
AB  - This article addresses the role of platelet membrane phosphatidylserine (PS) in
      regulating the production of thrombin, the central regulatory molecule of blood
      coagulation. PS is normally located on the cytoplasmic face of the resting
      platelet membrane but appears on the plasma-oriented surface of discrete membrane
      vesicles that derive from activated platelets. Thrombin, the central molecule of
      coagulation, is produced from prothrombin by a complex ("prothrombinase") between
      factor Xa and its protein cofactor (factor V(a)) that forms on platelet-derived
      membranes. This complex enhances the rate of activation of prothrombin to
      thrombin by roughly 150,000 fold relative to factor X(a) in solution. It is
      widely accepted that the negatively charged surface of PS-containing platelet
      derived membranes is at least partly responsible for this rate enhancement,
      although there is not universal agreement on mechanism by which this occurs. Our
      efforts have led to an alternative view, namely that PS molecules bind to
      discrete regulatory sites on both factors X(a) and V(a) and allosterically alter
      their proteolytic and cofactor activities. In this view, exposure of PS on the
      surface of activated platelet vesicles is a key regulatory event in blood
      coagulation, and PS serves as a second messenger in this regulatory process. This
      article reviews our knowledge of the prothrombinase reaction and summarizes
      recent evidence leading to this alternative viewpoint. This viewpoint suggests a
      key role for PS both in normal hemostasis and in thrombotic disease.

PMID- 12814645
TI  - Ligand-targeted liposomal anticancer drugs.
AB  - Antibody or ligand-mediated targeting of liposomal anticancer drugs to antigens
      expressed selectively or over-expressed on tumor cells is increasingly being
      recognized as an effective strategy for increasing the therapeutic indices of
      anticancer drugs. This review summarizes some recent advances in the field of
      ligand-targeted liposomes (LTLs) for the delivery of anticancer drugs. New
      approaches used in the design and optimization of LTLs is discussed and the
      advantages and potential problems associated with their therapeutic applications
      are described. New technologies are widening the spectrum of ligands available
      for targeting and are allowing choices to be made regarding affinity,
      internalization and size. The time is rapidly approaching where we will see
      translation of anticancer drugs entrapped in LTLs to the clinic.

PMID- 12814646
TI  - An ecto-protein tyrosine phosphatase of Entamoeba histolytica induces cellular
      detachment by disruption of actin filaments in HeLa cells.
AB  - Actin cytoskeleton disruption in host cells has been demonstrated for PTPases
      from pathogenic microorganisms. In this work, we analysed whether the secreted
      acid phosphatase from Entamoeba histolytica has phosphotyrosine phosphatase
      activity and the possibility that this activity may participate in damaging host
      cells. The secreted acid phosphatase of E. histolytica, which catalyses p
      nitrophenyl phosphate hydrolysis at acid pH values, was found to have
      phosphotyrosine phosphatase activity. The enzymatic properties of phosphotyrosine
      phosphatase and acid phosphatase were virtually identical and included: Km values
      of 10 x 10(-4) M, no requirement for divalent cations, and sensitivity to
      molybdate, vanadate, and tungstate. The phosphotyrosyl phosphatase activity
      caused significant levels of cell rounding and detachment correlating with
      disruption of the actin stress fibres in HeLa cells. Thus, our data suggest that
      secreted phosphotyrosine phosphatase could play a cytotoxic role during amoebic
      infection.

PMID- 12814647
TI  - Analysis of the Sarcocystis neurona microneme protein SnMIC10: protein
      characteristics and expression during intracellular development.
AB  - Sarcocystis neurona, an apicomplexan parasite, is the primary causative agent of
      equine protozoal myeloencephalitis. Like other members of the Apicomplexa, S.
      neurona zoites possess secretory organelles that contain proteins necessary for
      host cell invasion and intracellular survival. From a collection of S. neurona
      expressed sequence tags, we identified a sequence encoding a putative microneme
      protein based on similarity to Toxoplasma gondii MIC10 (TgMIC10). Pairwise
      sequence alignments of SnMIC10 to TgMIC10 and NcMIC10 from Neospora caninum
      revealed approximately 33% identity to both orthologues. The open reading frame
      of the S. neurona gene encodes a 255 amino acid protein with a predicted 39
      residue signal peptide. Like TgMIC10 and NcMIC10, SnMIC10 is predicted to be
      hydrophilic, highly alpha-helical in structure, and devoid of identifiable
      adhesive domains. Antibodies raised against recombinant SnMIC10 recognised a
      protein band with an apparent molecular weight of 24 kDa in Western blots of S.
      neurona merozoites, consistent with the size predicted for SnMIC10. In vitro
      secretion assays demonstrated that this protein is secreted by extracellular
      merozoites in a temperature-dependent manner. Indirect immunofluorescence
      analysis of SnMIC10 showed a polar labelling pattern, which is consistent with
      the apical position of the micronemes, and immunoelectron microscopy provided
      definitive localisation of the protein to these secretory organelles. Further
      analysis of SnMIC10 in intracellular parasites revealed that expression of this
      protein is temporally regulated during endopolygeny, supporting the view that
      micronemes are only needed during host cell invasion. Collectively, the data
      indicate that SnMIC10 is a microneme protein that is part of the
      excreted/secreted antigen fraction of S. neurona. Identification and
      characterisation of additional S. neurona microneme antigens and comparisons to
      orthologues in other Apicomplexa could provide further insight into the functions
      that these proteins serve during invasion of host cells.

PMID- 12814648
TI  - Anopheles gambiae collagen IV genes: cloning, phylogeny and midgut expression
      associated with blood feeding and Plasmodium infection.
AB  - A prerequisite for understanding the role that mosquito midgut extracellular
      matrix molecules play in malaria parasite development is proper isolation and
      characterisation of the genes coding for components of the basal lamina. Here we
      have identified genes coding for alpha1 and alpha2 chains of collagen IV from the
      major malaria vector, Anopheles gambiae. Conserved sequences in the terminal NC1
      domain were used to obtain partial gene sequences of this functional region, and
      full sequence was isolated from a pupal cDNA library. In a DNA-derived phylogeny,
      the alpha1 and alpha2 chains cluster with dipteran orthologs, and the alpha2 is
      ancestral. The expression of collagen alpha1(IV) peaked during the pupal stage of
      mosquito development, and was expressed continuously in the adult female
      following a blood meal with a further rise detected in older mosquitoes. Collagen
      alpha1(IV) is also upregulated when the early oocyst of Plasmodium yoelii was
      developing within the mosquito midgut and may contribute to a larger wound
      healing response. A model describing the expression of basal lamina proteins
      during oocyst development is presented, and we hypothesise that the development
      of new basal lamina between the oocyst and midgut epithelium is akin to a wound
      healing process.

PMID- 12814649
TI  - Molecular characterisation of EmTFP250: a novel member of the TRAP protein family
      in Eimeria maxima.
AB  - We have previously described a high molecular mass, asexual stage antigen from
      Eimeria maxima (EmTFP250), implicated as a target of maternal antibodies produced
      by breeding hens infected with this protozoan parasite. Following partial
      purification of the protein by ion exchange chromatography, N-terminal and
      internal peptide sequences were generated and used in the design of degenerate
      PCR primers. Using a rapid amplification of cDNA ends PCR-based strategy, the
      cDNA encoding EmTFP250 has been cloned and sequenced. Translation predicts a
      mature polypeptide with a molecular mass of 246kDa and an isoelectric point of
      4.2. Analysis of the amino acid sequence has revealed a novel member of the TRAP
      (thrombospondin-related anonymous protein) family, containing 16 thrombospondin
      type-1 repeats and 31 epidermal growth factor-like calcium binding domains.
      EmTFP250 also contains two low complex, hydrophilic regions rich in glutamic acid
      and glycine residues, and a transmembrane domain/cytosolic tail associated with
      parasite gliding motility that is highly conserved within apicomplexan microneme
      proteins. The protein has 61% identity (71% similarity) with EtMIC4, a 218kDa
      microneme protein of Eimeria tenella also rich in epidermal growth factor-like
      and thrombospondin type-1 domains. Using Southern blotting, the gene encoding
      EmTFP250 has been determined to be present as a single copy within the genome,
      and reverse transcriptase-PCR has shown that expression is confined to the
      asexual stages of development. By employing a PCR-based method, a region of the
      E. maxima Houghton strain EmTFP250 gene was found conserved in Australian
      isolates of several (at least four) Eimeria species that parasitise chickens. The
      characterisation of EmTFP250 adds to the expanding apicomplexan TRAP family and
      suggests a functional significance for the protein.

PMID- 12814650
TI  - Altered T helper responses in CD40 and interleukin-12 deficient mice reveal a
      critical role for Th1 responses in eliminating the helminth parasite Taenia
      crassiceps.
AB  - A key feature of helminth infections is the induction of strong Th2-biased immune
      responses in their hosts. We have previously found that Th2-like responses
      mediate susceptibility to the helminth parasite Taenia crassiceps, probably by
      inhibiting Th1 responses required for the development of protective immunity
      against this parasite. Here we show that mice lacking interleukin-12p35 (IL-12p35
      /-) following T. crassiceps infection, failed to mount a Th1 response, but
      developed a strong Th2-type response, produced higher levels of IgG1, IgE,
      interleukin-4, interleukin-5 as well as interleukin-13 than wild-type mice, and
      became highly susceptible to the larval stage of this cestode. In contrast,
      similarly-infected CD40 deficient BALB/c mice (CD40-/-) displayed impairment of
      both Th1 and Th2-type responses associated with low levels of interferon-gamma as
      well as IgE, interleukin-4, interleukin-5 and interleukin-13, but efficiently
      controlled T. crassiceps infection. Together, these findings suggest a
      detrimental role for Th2-biased responses during the larval stage of T.
      crassiceps infection. Furthermore, they also suggest a pivotal role for CD40 in
      developing Th2-type responses.

PMID- 12814651
TI  - In vitro induction of microglial and endothelial cell apoptosis by cerebrospinal
      fluids from patients with human African trypanosomiasis.
AB  - In human African trypanosomiasis, trypanosomes first develop in the blood and
      lymph (Stage 1), then spread to the central nervous system (CNS) (Stage 2).
      Disruption of the blood-brain barrier of unknown mechanism occurs in Stage 2
      disease. The hypothesis that cerebrospinal fluids (CSF) from African
      trypanosomiasis patients might contain factor(s) able to induce apoptosis in
      endothelial cells led us to evaluate this effect by two methods, the TdT-mediated
      dUTP nick end labelling (TUNEL) method and the measurement of soluble nucleosomes
      released by apoptotic cells in culture supernatant by ELISA. Apoptosis induction
      by CSF was also studied with microglial cells, the resident macrophages in the
      brain, which participate in the blood-brain barrier in the perivascular area. In
      contrast with control CSF, African trypanosomiasis patients' CSF induced
      apoptosis in both microglial and endothelial cells. The results obtained with the
      two methods correlated well, and showed that Stage 2 CSF induced apoptosis at
      higher levels in microglial cells, whereas the disease stage was not decisive for
      apoptosis induction in endothelial cells. We measured soluble Fas ligand (sFasL)
      and anti-Fas antibodies levels, two potent inducers of the Fas signalling pathway
      leading to apoptosis, in CSF from African trypanosomiasis patients and controls.
      CSF from African trypanosomiasis patients contained sFasL, and anti-Fas
      antibodies at higher levels than in controls. Stage 2 CSF contained more sFasL
      than Stage 1 CSF, and anti-Fas antibodies were detected only in Stage 2 CSF.
      Caspase-8 inhibitor effect and statistical data suggest that other pro-apoptotic
      factors may be involved in some CSF-induced apoptosis. Apoptosis induction may
      participate in the pathogenesis during African trypanosomiasis, and the presence
      of sFasL and anti-Fas antibodies may provide new tools for diagnosis and
      prognosis of the disease.

PMID- 12814652
TI  - Characterisation of a Rho homologue of Schistosoma mansoni.
AB  - The development and survival of the helminth parasite, Schistosoma mansoni, is
      dependent on its ability to interpret signals from its environment. Currently,
      little is known about signal transduction in schistosomes. Rho is a member of a
      super-family of small GTP-binding proteins. Rho is involved in a number of cell
      signalling pathways with effects on actin cytoskeleton organisation, gene
      transcription, cell cycle progression, and membrane trafficking. We have cloned
      an S. mansoni protein (Rho1) that has 71-75% identity and approximately 85%
      similarity with human Rho A, B, and C proteins. We have optimised expression of
      recombinant S. mansoni Rho1 protein in Escherichia coli by co-expression with
      rare tRNAs. Western blot analysis results showed expression of Rho1 protein in
      adult worm stages especially female worms. In vitro prenylation of recombinant S.
      mansoni Rho1 determined that, similar to Rho from other organisms, Rho1 is
      geranynlgeranylated but not farnesylated. A search of the gene database indicates
      that Rho GTPases exist as a small family in S. mansoni including orthologues of
      Rho, Cdc42, and Rac. These data suggest that S. mansoni Rho1 plays a role in
      signalling in adult worms, especially females.

PMID- 12814653
TI  - Phylogeny and classification of the Digenea (Platyhelminthes: Trematoda).
AB  - Complete small subunit ribosomal RNA gene (ssrDNA) and partial (D1-D3) large
      subunit ribosomal RNA gene (lsrDNA) sequences were used to estimate the phylogeny
      of the Digenea via maximum parsimony and Bayesian inference. Here we contribute
      80 new ssrDNA and 124 new lsrDNA sequences. Fully complementary data sets of the
      two genes were assembled from newly generated and previously published sequences
      and comprised 163 digenean taxa representing 77 nominal families and seven
      aspidogastrean outgroup taxa representing three families. Analyses were conducted
      on the genes independently as well as combined and separate analyses including
      only the higher plagiorchiidan taxa were performed using a reduced-taxon
      alignment including additional characters that could not be otherwise
      unambiguously aligned. The combined data analyses yielded the most strongly
      supported results and differences between the two methods of analysis were
      primarily in their degree of resolution. The Bayesian analysis including all taxa
      and characters, and incorporating a model of nucleotide substitution (general
      time-reversible with among-site rate heterogeneity), was considered the best
      estimate of the phylogeny and was used to evaluate their classification and
      evolution. In broad terms, the Digenea forms a dichotomy that is split between a
      lineage leading to the Brachylaimoidea, Diplostomoidea and Schistosomatoidea
      (collectively the Diplostomida nomen novum (nom. nov.)) and the remainder of the
      Digenea (the Plagiorchiida), in which the Bivesiculata nom. nov. and
      Transversotremata nom. nov. form the two most basal lineages, followed by the
      Hemiurata. The remainder of the Plagiorchiida forms a large number of independent
      lineages leading to the crown clade Xiphidiata nom. nov. that comprises the
      Allocreadioidea, Gorgoderoidea, Microphalloidea and Plagiorchioidea, which are
      united by the presence of a penetrating stylet in their cercariae. Although a
      majority of families and to a lesser degree, superfamilies are supported as
      currently defined, the traditional divisions of the Echinostomida, Plagiorchiida
      and Strigeida were found to comprise non-natural assemblages. Therefore, the
      membership of established higher taxa are emended, new taxa erected and a
      revised, phylogenetically based classification proposed and discussed in light of
      ontogeny, morphology and taxonomic history.

PMID- 12814654
TI  - Indinavir reduces Cryptosporidium parvum infection in both in vitro and in vivo
      models.
AB  - The use of highly active antiretroviral therapy in persons with acquired
      immunodeficiency syndrome has reduced the prevalence of infection with
      Cryptosporidium parvum and the length and severity of its clinical course. This
      effect has in most cases been attributed to the recovery of the host immunity;
      however, some works suggest that human immunodeficiency virus protease
      inhibitors, indinavir in particular, which is one of the human immunodeficiency
      virus protease inhibitors used in highly active antiretroviral therapy, may be
      capable of controlling Microsporidia and Cryptosporidium infections, which are
      refractory to other treatments. The objective of the present study was to
      investigate the effect of human immunodeficiency virus protease inhibitors on C.
      parvum infections. Since preliminary experiments using ritonavir, saquinavir, and
      indinavir showed a drastic reduction of C. parvum infection both in vivo
      (neonatal Balb/c mice) and in vitro (human ileocecal adenocarcinoma tumour cell
      line) models, indinavir alone was tested in successive experiments. In vitro, the
      treatment of the sporulated oocysts with different concentrations of indinavir
      reduced the percentage of human ileocecal adenocarcinoma tumour cell line
      infected cells in a dose-dependent manner. For established infection, the
      treatment with 50 microM of indinavir decreased the percentage of infected cells
      in a time-dependent manner. In vivo, mice treated with indinavir at the same time
      they were infected with the oocysts showed a 93% reduction in the number of
      oocysts present in the entire intestinal contents and a 91% reduction in the
      number of intracellular parasites in the ileum. For established infection,
      indinavir treatment reduced the number of oocysts in the entire intestinal
      content by about 50% and the number of intracellular parasites in the ileum by
      about 70%. These data show that indinavir directly interferes with the cycle of
      C. parvum, resulting in a marked reduction in oocyst shedding and in the number
      of intracellular parasites. Protease inhibitors could be considered as good
      candidates for the treatment of cyptosporidiosis in immunosuppressed persons.

PMID- 12814655
TI  - Pyrosequencing analysis identifies discrete populations of Haemonchus contortus
      from small ruminants.
AB  - The genus Haemonchus consists of blood-sucking parasitic nematodes in the
      abomasum of ruminants. Members of this genus are responsible for extensive
      production losses, particularly of small ruminants in the tropics but are also
      found in temperate regions. In this study, we examined the internal transcribed
      spacers-1 and -2 of rRNA in Haemonchus spp. The rRNA region spanning the internal
      transcribed spacers-1, -2 and the 5.8S rRNA gene was amplified by PCR from each
      of 10 worms from Swedish sheep, a Swedish goat and Kenyan sheep. The fragments
      were sequenced and examined with respect to genetic differences fixed among the
      three isolates. These and additional worms were further analysed with
      Pyrosequencing technology. This technique allowed us to rapidly analyse 110
      individuals in three putative polymorphic nucleotide positions that were
      initially identified with dideoxy sequencing. The geographical isolates could to
      a large extent be genetically distinguished, but none of the polymorphic
      positions were consistent among all individuals within each isolate. Furthermore
      an alignment of our sequences and a consensus sequence published for Haemonchus
      contortus revealed two differences in positions 123 and 196 in internal
      transcribed spacers-2. Although these positions were previously reported as
      heterogenic, no polymorphism was detected among the 30 worms sequenced in the
      present study. Modelling of the internal transcribed spacers-2 secondary
      structure based on our data also identified a new putative long-range
      interaction. The isolates are best described as populations. In conclusion,
      consistent differences were not identified and the studied isolates are therefore
      best described as discrete populations. This study also reveals for the first
      time the potential of Pyrosequencing technology as a tool in the analysis of
      nematode population genetics.

PMID- 12814656
TI  - Part I: parkin-associated proteins and Parkinson's disease.
AB  - Parkin is an E3 ligase that plays an important role in the ubiquitin/proteosome
      pathway responsible for protein degradation events. Mutations in parkin result in
      a loss-of-function and lead to Parkinson's disease, a progressive neurological
      disorder of movement. Presumably, this occurs due to the toxic build-up of
      proteins that are no longer effectively cleared/degraded by the parkin-dependent
      ubiqutin/proteosome pathway. To date, three types of proteins have been shown to
      interact with parkin. Firstly, the E2 ubiquitin conjugating proteins called UbcH7
      and UbcH8 interact with parkin. Secondly, putative substrates interacting with
      parkin include a synaptic vesicle associated GTPase named CDCrel-1; a G protein
      coupled receptor named Pael; a novel from of alpha-synuclein; and an alpha
      synuclein interacting protein synphilin-1. Thirdly and more recently, a PDZ
      domain containing scaffolding protein CASK/Lin2 has been shown to interact with
      the PDZ binding motif of parkin. A network of PDZ-interacting proteins has
      potential to form a complex web of molecules that surround parkin and regulate
      its subcellular localisation and function.

PMID- 12814657
TI  - Part II: alpha-synuclein and its molecular pathophysiological role in
      neurodegenerative disease.
AB  - Alpha-synuclein (alphaSN) brain pathology is a conspicuous feature of several
      neurodegenerative diseases. These include prevalent conditions such as
      Parkinson's disease (PD), dementia with Lewy bodies (DLB), and the Lewy body
      variant of Alzheimer's disease (LBVAD), as well as rarer conditions including
      multiple systems atrophy (MSA), and neurodegeneration with brain iron
      accumulation type-1 (NBIA-1). Common in these diseases, some referred to as alpha
      synucleinopathies, are microscopic proteinaceous insoluble inclusions in neurons
      and glia that are composed largely of fibrillar aggregates of alphaSN. This
      molecular form of alphaSN contrasts sharply with normal alphaSN, which is an
      abundant soluble presynaptic protein in brain neurons. alphaSN is a highly
      conserved protein in vertebrates and only seven of its 140 amino acids differ
      between human and mouse. Flies lack an alphaSN gene. Implicated in neurotoxicity
      are two alphaSN mutants (A53T and A30P) that cause extremely rare familial forms
      of PD, alphaSN fibrils and protofibrils, soluble protein complexes of alphaSN
      with 14-3-3 protein, and phosphorylated, nitrosylated, and ubiquitylated alphaSN
      species. Unlike rare forms of fPD caused by mutations in alphaSN, disease
      mechanisms in most alpha-synucleinopathies implicate wildtype alphaSN and seem to
      converge around oxidative damage and impairments in protein catabolism. It is not
      known whether these causalities involve alphaSN from the beginning, but defects
      in the handling of this protein seem to contribute to disease progression because
      accumulation of toxic alphaSN forms damage neurons. Here, we summarize the main
      structural features of alphaSN and its functions, and discuss the molecular
      alphaSN species implicated in human disease and transgenic animal models of alpha
      synucleinopathy in fly and rodents.

PMID- 12814658
TI  - Targeting striatal cholinergic interneurons in Parkinson's disease: focus on
      metabotropic glutamate receptors.
AB  - In the early sixties, anticholinergic drugs were introduced in the
      pharmacological treatment of Parkinson's disease (PD). The rationale behind their
      utilisation in the treatment of the disease was based on the evidence of an
      imbalance between the dopaminergic inputs and the intrinsic cholinergic
      innervation within the striatum. Metabotropic glutamate (mGlu) receptors have
      been shown to play a key role in striatal function both in physiological
      conditions and in experimental models of diseases affecting this brain area.
      Indeed, compelling electrophysiological and morphological evidence shows that
      mGlu receptors are highly expressed at cellular level and exert a profound
      modulatory role on cholinergic interneurons excitability. This review will
      provide a brief survey of studies on the localization and function of mGlu
      receptors in cholinergic interneurons. The potential relevance of these findings
      in the control of motor function and in the treatment of PD will be discussed.

PMID- 12814660
TI  - In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex
      by midbrain-raphe nuclei: role of 5-HT1A receptors.
AB  - The ventral part of the medial prefrontal cortex (mPFC) plays an important role
      in mood and cognition. This study examined the effect of the 5-HT in this region
      by measuring the electrophysiological response of ventral mPFC neurones to
      electrical stimulation of the dorsal and median raphe nuclei (DRN and MRN), which
      are the source of the 5-HT input. DRN or MRN stimulation evoked a consistent,
      short-latency, post-stimulus inhibition in the majority of ventral mPFC neurones
      tested (DRN: 44/73 neurones; MRN: 24/31 neurones). Some neurones responded to DRN
      or MRN stimulation with antidromic spikes indicating that they were mPFC-raphe
      projection neurones. Both DRN- and MRN-evoked inhibitions were attenuated by
      systemic administration of the 5-HT1A antagonist WAY 100635 (0.1 mg/kg i.v.). DRN
      evoked inhibition was also attenuated by iontophoretic application of WAY 100635
      and by systemic administration of the 5-HT1A antagonist, NAD-299 (4 mg/kg i.v.)
      but not the 5-HT2 antagonist ketanserin (4 mg/kg, i.v.). These data suggest that
      DRN and MRN 5-HT neurones inhibit neurones in the ventral mPFC via activation of
      5-HT1A receptors. Some of these mPFC neurones may be part of a 5-HT1A receptor
      controlled postsynaptic feedback loop to the DRN and MRN.

PMID- 12814659
TI  - The in vitro and in vivo enantioselectivity of etomidate implicates the GABAA
      receptor in general anaesthesia.
AB  - General anaesthetics exhibiting enantioselectivity afford valuable tools to
      assess the fundamental mechanisms underlying anaesthesia. Here, we characterised
      the actions of the R-(+)- and S-(-)-enantiomers of etomidate. In mice and
      tadpoles, R-(+)-etomidate was more potent (approximately 10-fold) than S-(-)
      etomidate in producing loss of the righting reflex. In electrophysiological and
      radioligand binding assays, the enantiomers of etomidate positively regulated
      GABAA receptor function at anaesthetic concentrations and with an
      enantioselectivity paralleling their in vivo activity. GABA-evoked currents
      mediated by human recombinant GABAA receptors were potentiated by either R-(+)-
      or S-(-)-etomidate in a manner dependent upon receptor subunit composition. A
      direct, GABA-mimetic, effect was similarly subunit dependent. Modulation of GABA
      receptor activity was selective; R-(+)-etomidate inhibited nicotinic
      acetylcholine, or 5-hydroxytryptamine3 receptor subtypes only at supra-clinical
      concentrations and ionotropic glutamate receptor isoforms were essentially
      unaffected. Acting upon reticulothalamic neurones in rat brain slices, R-(+)
      etomidate prolonged the duration of miniature IPSCs and modestly enhanced their
      peak amplitude. S-(-)-etomidate exerted qualitatively similar, but weaker,
      actions. In a model of locomotor activity, fictive swimming in Xenopus laevis
      tadpoles, R-(+)- but not S-(-)-etomidate exerted a depressant influence via
      enhancement of GABAergic neurotransmission. Collectively, these observations
      strongly implicate the GABAA receptor as a molecular target relevant to the
      anaesthetic action of etomidate.

PMID- 12814661
TI  - The GBeta5 subunit that associates with the R7 subfamily of RGS proteins
      regulates mu-opioid effects.
AB  - The Gbeta5 protein, which is similar in sequence to other G-protein beta
      subunits, mainly associates with the G-protein gamma-like (GGL) domains of the R7
      subfamily of regulators of G-protein signalling (RGS) proteins. This paper
      reports the presence of the Gbeta5 protein and its mRNA in all areas of mouse
      CNS, and also its involvement in the cellular signals initiated at mu- and delta
      opioid receptors. The expression of Gbeta5 and RGS9-2 proteins (member of the R7
      subfamily of RGS) was reduced by blocking their mRNAs with antisense
      oligodeoxynucleotides (ODN). Knock-down of these proteins enhanced the potency
      and duration of antinociception promoted by morphine and [D-Ala2, N-MePhe4,Gly
      ol5]-enkephalin (DAMGO), agonists at mu opioid receptors. However, the activity
      of the selective agonist at delta opioid receptors, [D-Pen(2,5)]-encephalin
      (DPDPE), appeared to be reduced. A single intracerebroventricular (i.c.v.) ED80
      analgesic dose of morphine gave rise to acute tolerance in control mice, but did
      not promote tolerance in Gbeta5 or RGS9-2 knock-down animals. In a model of
      sustained morphine treatment, the impairment of Gbeta5 proteins facilitated the
      development of tolerance. This treatment did not alter the incidence of jumping
      behaviour precipitated by naloxone 3 days after commencing with chronic morphine.
      These results show differences in the signalling regulation of G-proteins when
      activated by mu or delta opioid agonists. For mu opioid receptors, acute
      tolerance, but probably not long-term tolerance, appears to depend on the
      function of Gbeta5 subunits and associated RGS proteins.

PMID- 12814662
TI  - Functional evidence for interaction between prostaglandin EP3 and kappa-opioid
      receptor pathways in tactile pain induced by human immunodeficiency virus type-1
      (HIV-1) glycoprotein gp120.
AB  - HIV-1 glycoprotein gp120 administered intrathecally induces tactile pain
      (allodynia) in animals. In the present study, we investigated the mechanism of
      gp120-induced allodynia and possible functional connections with factors
      modulating pain transmission at the spinal level. Gp120 evoked allodynia in a
      dose-dependent manner with the maximum effect at 1 pg/mouse, and stimulated a
      rapid increase in intracellular free Ca2+ concentration ([Ca2+]i) in the dorsal
      horn cells of the spinal cord. These responses evoked by gp120 were blocked by
      galactocerebroside. The gp120-induced allodynia was also attenuated by the non
      steroidal anti-inflammatory drug indomethacin, which inhibits prostaglandin
      synthesis, and did not develop in mice lacking the EP3 prostaglandin E receptor
      subtype (EP3(-/-)). Pretreatment of spinal slices with indomethacin dose
      dependently decreased the percentage of the cells that showed increased [Ca2+]i
      in response to gp120, and the decrease was reversed by addition of the selective
      EP3 agonist ONO-AE-248. The kappa-opioid agonist U-50,488 significantly enhanced
      the gp120-stimulated increase in [Ca2+]i in spinal slices prepared from EP3(-/-)
      mice, and the simultaneous addition of U-50,488 with gp120 reproduced the gp120
      induced allodynia in EP3(-/-) mice. These results suggest that gp120 induced
      allodynia by increasing [Ca2+]i, concomitant with activation of prostanoid EP3
      and kappa-opioid receptors in the spinal cord.

PMID- 12814663
TI  - Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences
      on cocaine-induced reward and psychomotor stimulation in adulthood.
AB  - Pre-exposure to psychostimulants enhances the rewarding and psychomotor
      stimulating effects of subsequent drug exposure. Currently, there is a prevalence
      of adolescent exposure to the psychostimulants methylphenidate (MPD) and 3,4
      methylenedioxymethamphetamine (MDMA). However, there is a paucity of
      investigation concerning the long-term behavioral consequences of exposure to
      these stimulants during adolescence. The aim of the present study was to
      investigate the effect of MPD and MDMA exposure in adolescence on cocaine-induced
      reward and psychomotor stimulation in adulthood. Adolescent Swiss-Webster mice
      received intraperitoneal injections of saline, MPD (10 mg/kg) or MDMA (10 mg/kg)
      from PD 26 to PD 32. Animal weights were monitored during and after drug
      administration. One month later, cocaine-induced conditioned place preference
      (CPP) and locomotor activity (LMA) were investigated. MPD and MDMA inhibited
      weight increase from PD 28 to PD 39 compared to the saline group, but weights
      amongst the three groups equalized by PD 46. MDMA exposure resulted in the same
      magnitude of cocaine (20 mg/kg)-induced CPP as saline exposure; however, MPD
      exposure caused significantly less CPP. Two weeks following extinction of CPP and
      withdrawal from cocaine, a priming injection of cocaine (5 mg/kg) reinstated
      significantly higher CPP in the MPD and MDMA groups than in the saline group. In
      the LMA experiments, cocaine (15 mg/kg) was administered for 5 consecutive days.
      On days 1 and 5, cocaine-induced hyperlocomotion in the MPD group was
      significantly higher than in the saline and MDMA groups. After a 2-week
      withdrawal period, cocaine (5 mg/kg) evoked significantly higher LMA responses in
      the MPD and MDMA groups compared to the saline group. Results suggest that
      exposure of mice to both MPD and MDMA during adolescence involves long-lasting
      neural adaptations, manifested as sensitized responses to cocaine-induced reward
      and psychomotor stimulation following cocaine withdrawal.

PMID- 12814664
TI  - Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in
      human dentate gyrus.
AB  - In spite of their popular uses as recreational drugs and their potential
      therapeutic uses, little direct information has been obtained about the synaptic
      effects of cannabinoids in the human brain. In the present study, patch-clamp
      recordings were performed on granule cells of the human dentate gyrus and the
      effects of cannabinoid receptor-1 (CB1) activation on inhibitory synaptic
      activity were examined. Activation of CB1 receptors by WIN55212-2 significantly
      suppressed both frequency and amplitude of spontaneous inhibitory synaptic
      currents (IPSCs) to about 50% of control. The suppressive effects were completely
      abolished in the presence of the CB1 receptor antagonist, AM251. WIN55212-2 also
      suppressed evoked IPSCs. However, neither frequency nor amplitude of miniature
      IPSCs were affected by WIN55212-2. These results provide electrophysiological
      evidence for the role of CB1 receptors in modulating inhibitory activity in human
      dentate gyrus.

PMID- 12814665
TI  - Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.
AB  - CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and
      carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic
      variation in CYP2B6 affects smoking cessation rates. The aim of this study was to
      compare CYP2B6 expression in brains of human smokers and non-smokers and
      alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region
      specific, and was observed in both neurons and astrocytes. CYP2B6 levels were
      higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje
      cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics.
      Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of
      smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8
      fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere
      (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced
      hepatic enzyme levels, stability and activity. Preliminary genotyping of this
      small sample (n=24) suggested that individuals with the CC genotype had higher
      brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity
      in smokers and alcoholics may cause altered sensitivity to centrally acting
      drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and
      contribute to central tolerance to nicotine.

PMID- 12814666
TI  - Diverse actions of neonicotinoids on chicken alpha7, alpha4beta2 and Drosophila
      chicken SADbeta2 and ALSbeta2 hybrid nicotinic acetylcholine receptors expressed
      in Xenopus laevis oocytes.
AB  - The 2-nitroimino-imidazolidine and related moieties are structural features of
      neonicotinoid insecticides acting on nicotinic acetylcholine receptors (nicotinic
      AChRs). To evaluate these moieties in neonicotinoid interactions with nicotinic
      AChR alpha subunits, the actions of imidacloprid and related compounds on the
      chicken alpha7, alpha4beta2 and Drosophila melanogaster-chicken hybrid (SADbeta2
      and ALSbeta2) receptors expressed in Xenopus laevis oocytes were studied by
      voltage-clamp electrophysiology. Imidacloprid and nitenpyram were partial
      agonists and a nitromethylene analog of imidacloprid (CH-IMI) was a full agonist
      of the alpha7 receptor, whereas their agonist actions on the alpha4beta2 receptor
      were very weak, contrasting with full agonist actions of DN-IMI, a desnitro
      derivative of imidacloprid. The neonicotinoids and DN-IMI were either full or
      partial agonists of the SADbeta2 receptors. Nitenpyram and DN-IMI were partial
      agonists of the ALSbeta2 receptor, whereas imidacloprid and CH-IMI scarcely
      activated the ALSbeta2 receptor. Imidacloprid and CH-IMI in fact suppressed ACh
      induced responses of the ALSbeta2 receptor, whereas imidacloprid potentiated and
      CH-IMI suppressed ACh-induced responses of the alpha4beta2 receptor. These
      results suggest that interactions with alpha subunits of the 2-nitroimino
      imidazolidine moiety of imidacloprid play a role in determining not only agonist
      and antagonist actions on all four receptors, but also the potentiation of ACh
      induced responses of the alpha4beta2 receptor.

PMID- 12814667
TI  - 2-Alkylthio-substituted platelet P2Y12 receptor antagonists reveal
      pharmacological identity between the rat brain Gi-linked ADP receptors and P2Y12.
AB  - The Gi-linked platelet ADP receptor, now designated as P2Y12, accounts for ADP
      induced inhibition of adenylyl cyclase in platelets and certain clonal rat cell
      lines. The pharmacology of this receptor is well characterized. Based on the
      functional approach of [35S]GTPgammaS autoradiography, we recently disclosed the
      widespread presence of Gi-linked ADP receptors in the rat nervous system. Based
      on initial pharmacological analysis, these receptors were strikingly similar with
      P2Y12. Here, we extend this analysis by comparing the potencies of six 2
      alkylthio-substituted ATP analogues, including the adenosine-aspartate conjugate
      2-hexylthio-AdoOC(O)Asp2 and five AR-C compounds (AR-C67085, AR-C69931, AR
      C78511, AR-C69581, AR-C70300) with wide range of affinities towards P2Y12, in
      reversing 2-methylthio-ADP stimulated G protein activity in rat brain sections
      and human platelet membranes. Closely matching pIC50 values (r2=0.99) revealed
      pharmacological similarity between the two receptors with one exception: AR
      C67085 more avidly recognized the platelet P2Y12. Further analysis of the rat
      brain pIC50 data against those available for three of the AR-C compounds in
      reversing P2Y12-mediated adenylyl cyclase inhibition in rat platelets (r2=0.96)
      and rat C6 glioma cells (r2=1.00) demonstrated that the three P2Y receptors are
      pharmacologically indistinguishable. We conclude that the rat brain Gi-linked ADP
      receptors, as revealed using [35S]GTPgammaS autoradiography, correspond to P2Y12.

PMID- 12814668
TI  - Sexually transmitted diseases (STDs)--a synoptic overview for urologists.
AB  - The classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis,
      chancroid and inguinal granuloma only account for a small proportion of all known
      STDs today. Other bacteria and viruses as well as yeasts, protozoa and epizoa
      must also be regarded as causative organisms of STD. Taken together, all sexually
      transmitted infections (STI) comprise more than 30 relevant STD pathogens.
      However, not all pathogens that can be sexually transmitted manifest diseases in
      the genitals and not all infections of the genitals are exclusively sexually
      transmitted. Concise information and tables summarising the diagnostic and
      therapeutic management of STDs in the field of Urology allow a synoptic overview
      and are in agreement with recent international guidelines of other specialties.
      Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and
      recommended regimens may be looked up here.

PMID- 12814669
TI  - DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer.
AB  - BACKGROUND: DD3(PCA3) is the most prostate cancer-specific gene described to
      date. To assess the clinical utility of DD3(PCA3) a time-resolved fluorescence
      based, quantitative RT-PCR analysis for DD3(PCA3) was developed. METHODS: The
      diagnostic potential of DD3(PCA3) was determined by quantitative measurement of
      DD3(PCA3) transcripts in non-malignant and malignant prostate specimens.
      Moreover, DD3(PCA3) transcripts were determined quantitatively in urine sediments
      obtained after prostatic massage. A cohort of 108 men, admitted for prostate
      biopsies based on a PSA of >3ng/ml, was studied. RESULTS: Prostate tumors showed
      a 66-fold up-regulation of DD3(PCA3) (median 158.4.10(5) copies/microg tissue
      RNA) when compared to benign prostate tissue (median 2.4.10(5) copies/microg
      tissue RNA). This up-regulation was found in more than 95% of prostate cancer
      specimens studied. These data revealed that specimens with less than 10% of
      cancer cells could be accurately discriminated from non-cancer tissues. Hence,
      detection of a small fraction of prostate cancer cells in a background of normal
      cells seemed feasible. Therefore, this DD3(PCA3)-based RT-PCR assay was used for
      the identification of prostate cancer in urine sediments obtained after prostatic
      massage. From 108 men with a serum PSA value >3ng/ml, 24 men were shown to have
      prostate cancer upon biopsy. Of these 24 men, 16 were shown to be positive for
      DD3(PCA3), indicating a sensitivity of the assay of 67%. Furthermore, a negative
      predictive value of 90% was calculated. CONCLUSION: The quantitative RT-PCR assay
      for DD3(PCA3) described, bears great promise as a tool for molecular urine
      analysis. It has great potential in reducing the number of unnecessary biopsies.
      A multi-center study using this DD3(PCA3) assay can provide the basis for the
      utility of molecular diagnostics in clinical urological practice.

PMID- 12814670
TI  - A seven-year follow-up of men following a benign prostate biopsy.
AB  - OBJECTIVES: To determine the incidence and clinical relevance of newly diagnosed
      cases of prostate cancer in a group of men who had an elevated PSA and benign
      prostate biopsy 7 years previously. PATIENTS AND METHOD: Patients under the age
      of 80 years with an elevated PSA who had had a benign prostate biopsy in the 12
      months between March 1, 1994 and February 28, 1995 were studied. One hundred and
      sixty four patients with a mean age of 66.8 years (range 47-79 years) were
      identified. The mean PSA for this group was 10.3ng/ml (range 4.1-81ng/ml). One
      hundred and fifty nine of the 164 (97%) hospital records were available for
      review and all but 21 (12.8%) of the General Practitioners were contacted.
      RESULTS: Eighteen (11%) of the original 164 patients were subsequently diagnosed
      with prostate cancer, 2 died from their disease. CONCLUSIONS: In a population
      where the follow-up of patients with a benign biopsy was arranged on clinical
      grounds alone, 11% of the study group were diagnosed with prostate cancer during
      a seven-year follow-up. Although some of these cancers appear to be slow growing,
      most of those diagnosed in the initial follow-up period were deemed to be
      clinically significant and a small proportion progressed rapidly to metastases.
      All patients who have an elevated PSA, but benign biopsy, should undergo a period
      of PSA monitoring until it is clear that their PSA is not rising. We propose an
      initial intensive monitoring period to avoid missing those with clinically
      aggressive disease.

PMID- 12814671
TI  - Value of power doppler and 3D vascular sonography as a method for diagnosis and
      staging of prostate cancer.
AB  - OBJECTIVES: To compare the value of Power Doppler Sonography (PDS) and B mode
      sonography in the diagnosis of prostate cancer and to assess the value of PDS to
      specify capsular effraction of the cancer. PATIENTS AND METHODS: 323 patients
      were investigated: 41 control subjects allowed the establishment of normal
      vascular semiology and 282 patients with suspected cancer (PSA >4ng/ml). Power
      Doppler Sonography with 3D reconstruction was used to describe Power Doppler
      Sonography features of normal or abnormal vessels. Three types of blood supply(a:
      regular avascular posterior peripheral margin, b: irregular avascular posterior
      peripheral margin, c: vessels crossing the posterior peripheral margin) were
      described as a function of the presumed stage of cancer (a: intraprostatic, b:
      undetermined, c: extraprostatic). Comparison with histology was performed on
      random biopsies without Doppler (282 cases) (median PSA level = 15.8ng/ml), on
      second biopsies indicated with PDS (72 cases), and radical prostatectomy
      specimens (63 cases). RESULTS: A cancer was diagnosed in 157 of the 282 patients
      (55.7%) with suspected cancer. The overall sensitivity of PDS in the initial
      diagnosis of prostatic cancer was 92.4% and its specificity was 72% (versus 87.9%
      and 57.6% for sonography alone respectively). The negative predictive value of
      PDS was elevated to 80.6% (p<0.0001). Targeting area presenting abnormal blood
      flow in any part of the prostate was useful to detect isoechoic or lesions in
      patients with first negative biopsy results (in 41 of 72 targeted patients with
      first negative biopsies with PDS a cancer was diagnosed: 58% of these cancers had
      less than 3 positive biopsies and 34% only one positive biopsy). The 3 vascular
      types a, b, c were evaluated prospectively in the detection of capsular
      effraction. The presence or absence of vessels crossing the capsule to determine
      an extracapsular extension was a significant sign (p<0.0001). Capsular effraction
      was detected in 3 of the 27 cases (11%) of type a cancer and in 16 of the 18
      cases (87%) of type c cancer. CONCLUSION: PDS improves the accuracy of
      echographic imaging in the diagnosis of cancer. Combining first sextant biopsies
      and targeted areas presenting abnormal blood flow using PDS can increase cancer
      detection with an optimized number of biopsy cores. The risk of extracapsular
      involvement can be evaluated by the presence of vessels perforating the capsule.

PMID- 12814672
TI  - 11C-choline positron emission tomography for the evaluation after treatment of
      localized prostate cancer.
AB  - RATIONALE: The evaluation of the efficacy of the treatment of men with prostate
      cancer is largely based on post treatment levels of PSA. An increase in PSA or
      biochemical recurrence is the first sign of recurrent disease and precedes a
      clinically detectable recurrence by months to years. Digital rectal examination
      and conventional imaging techniques are not sensitive to detect a local
      recurrence. A metabolic imaging technique, which is not dependent on anatomical
      distortions, could be of use. In this study we investigated 11C-choline positron
      emission tomography (PET) for the evaluation after treatment of localized
      prostate cancer. METHODS: Thirty-six patients with localized prostate cancer,
      treated by either radical prostatectomy (n=20) or by external beam radiotherapy
      (n=16) were studied with 11C-choline PET. The results of PET were compared with
      the results of histology and with clinical follow up. RESULTS: Fourteen patients
      had no biochemical failure after therapy. 11C-choline PET was true negative in
      14/14 patients. Twenty-two patients had a biochemical failure. In the radical
      prostatectomy patients 11C-choline PET was true positive in 5/13 (38%) cases. In
      the external beam radiotherapy patients 11C-choline PET was true positive in 7/9
      (78%). The recurrent tumor was confirmed by biopsy or by bone scan in eleven of
      the twelve true positive patients. In ten patients with a negative 11C-choline
      PET scan, no recurrent tumor could be proven yet clinically, by biopsy or during
      follow up. CONCLUSION: 11C-choline PET is a feasible technique for evaluation of
      treatment for localized prostate cancer. The site of recurrence was detected
      correctly in 78% of the patients after external beam radiotherapy compared to 38%
      of the patients after radical prostatectomy. No positive PET scans were observed
      sofar in patients with a serum PSA <5ng/ml. Confirmatory studies and longer
      follow up are needed to determine the efficacy of 11C-choline PET compared to
      other imaging techniques.

PMID- 12814673
TI  - Brachytherapy for prostate cancer: a systematic review of clinical and cost
      effectiveness.
AB  - OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate
      cancer, and is increasingly being used in Europe and North America. METHODS: A
      systematic review of studies that compared clinical or cost effectiveness of
      prostate brachytherapy with radical prostatectomy or external beam radiation for
      patients with localised prostate cancer. RESULTS: No randomised controlled trials
      were identified, but five observational studies with comparable patient groups
      were included in the review. There were no valid data on overall or disease-free
      survival. There was no difference in disease-free survival based on PSA as a
      surrogate measure, or in rates of complications. No cost effectiveness studies
      were found. Based on Norwegian data, the one-year cost of the three treatment
      options seem fairly similar, while long term cost data are lacking due to lack of
      data on long term clinical outcome. CONCLUSION: The evidence on the clinical
      effectiveness of therapies for localised prostate cancer is scarce, but the
      outcome appears to be comparable for radical prostatectomy, external beam
      radiotherapy and brachytherapy.

PMID- 12814674
TI  - Significance of random bladder biopsies in superficial bladder cancer.
AB  - OBJECTIVES: We investigated to what extent biopsies of normal-appearing
      urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis)
      showed malignant disease and whether those findings had impact on therapeutical
      decisions. PATIENTS AND METHODS: 1033 consecutive patients presenting with Ta, T1
      or Tis (carcinoma in situ) superficial bladder tumors at increased risk for
      recurrence underwent multiple random biopsies from normal-appearing urothelium
      during transurethral resection (TUR). Patients with small, primary, singular
      tumors (smaller or equal to 1cm) were excluded from random biopsies. RESULTS: No
      tumor was found in the random biopsies of 905 patients (87.6%). 128 patients
      (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta:
      41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary
      tumor revealed no signs of malignancy, urothelial bladder cancer was detected in
      the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21
      patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis.
      Upstaging of the primary, resected tumor by histological examination of the
      random biopsy material occurred in 75 patients (7%). Altogether, due to the
      random biopsy results therapy was altered in 70 patients (6.8%) of our series: It
      changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and
      cystectomy in 15 patients. CONCLUSIONS: While the clinical significance of random
      biopsies is still controversial, random biopsy results had strong impact on
      therapeutical decisions in our series. Regarding random bladder biopsies a simple
      tool for the urologist to identify high risk groups of patients, we recommend
      them as part of the routine management of superficial bladder cancer.

PMID- 12814675
TI  - Reduced specificity of 5-ALA induced fluorescence in photodynamic diagnosis of
      transitional cell carcinoma after previous intravesical therapy.
AB  - OBJECTIVE: Photodynamic diagnosis (PDD) for the detection of bladder cancer has
      become a diagnostic tool in several hospitals. Several studies have reported
      different rates of false positive biopsies using 5-aminolevulinic acid induced
      fluorescence. In this study we evaluated the effect of previous intravesical
      therapy on the false positive biopsy rate. METHODS: Two hours prior to endoscopy
      1.5g ALA dissolved in 50ml 1.4% NaHCO(3) solution was instilled intravesically.
      For fluorescence excitation a blue light source (D-light, Karl Storz) was used.
      Under white and fluorescence light guidance, tumor locations were recorded, cold
      cup biopsies were taken and tumors were resected. Patients were divided into 3
      groups, last intravesical therapy (IVT) less than 6 months prior to PDD, last IVT
      longer than 6 months before PDD and no previous IVT. RESULTS: In total 917
      biopsies were taken in 249 procedures of fluorescent and non-fluorescent areas.
      White light endoscopy revealed 270 and PDD 378 of in total 390 tumors, resulting
      in a sensitivity of 97% and specificity of 49% for PDD. Pathologic evaluation
      considered 270 fluorescent biopsies as false positive. The rate of false positive
      biopsies was 25.7% in the group No IVT, 30.6% in the group PDD-IVT >6 months,
      whereas in the group "within 6 months after intravesical therapy" the rate was
      39.6% (p<0.025). When premalignant lesions such as dysplasia II are considered
      tumor the difference between the groups is even more significant (p<0.001).
      CONCLUSIONS: The procedure has a high sensitivity for superficial bladder cancer
      and decreases the number of overlooked lesions. Recent intravesical therapy
      results in significantly more false positive fluorescent biopsies. Since patient
      outcome might predominantly be determined by the early detection and subsequent
      treatment of (pre)malignant tissue we suggest that PDD is justified even shortly
      after intravesical therapy.

PMID- 12814676
TI  - Is there a role for bladder preserving strategies in the treatment of muscle
      invasive bladder cancer?
AB  - Single modality bladder sparing therapy for muscle-invasive bladder cancer,
      including transurethral resection, systemic chemotherapy or radiotherapy have
      been demonstrated to result in insufficient local control of the primary tumor as
      well as decreased long-term survival of the patients when compared to radical
      cystectomy. Therefore, multimodality treatment protocols that aim at bladder
      preservation and involve all of the aforementioned approaches have been
      established. Arguments for combining systemic chemotherapy with radiation are to
      sensitize tumor tissue to radiotherapy and to eradicate occult metastases that
      have already developed in as many as 50% of patients at the time of first
      diagnosis. It has been shown that the clinical outcome observed with this
      approach approximates that after radical cystectomy. Additionally, a substantial
      number of patients survive with an intact bladder. However, bladder preserving
      approaches are costly, and require close co-operation between different clinical
      specialists as well as very close follow-up. The good long-term results obtained
      after cystectomy and creation of an orthotopic neobladder make the possible
      advantage of a bladder preservation strategy questionable in consideration of
      quality of life issues. Additionally, side effects related to bladder sparing
      therapy may result in an increased morbidity and mortality in those patients who
      in fact need to undergo surgery due to recurrent or progressive disease.
      Multimodality bladder sparing treatment is a therapeutic option that can be
      offered to the patient at centres that have a dedicated multidisciplinary team at
      their disposal. However, radical cystectomy remains the standard of care for
      muscle-invasive bladder tumors.

PMID- 12814677
TI  - Immunotherapy for renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most prevalent malignancy within the kidney and
      the incidence is rising. Due to improved radiological evaluation over 50% of the
      renal cancers are found incidentally. Despite the fact that these incidentalomas
      are often confined to the kidney, around 50% of all patients diagnosed with
      kidney cancer will develop systemic disease. Metastatic RCC has a poor prognosis.
      Traditional treatment modalities like chemo- and radiotherapy show overall
      response percentages of 2-6%. In view of the observed spontaneous remissions of
      advanced renal cancer, immune mechanisms have been suggested to play a role in
      the natural disease course of RCC. At present, several non-specific cytokine
      regimens are used in the treatment of mRCC, e.g. interleukin-2 and interferon
      alpha, in combination or as monotherapy or in combination with substances like 13
      cis-retinoic acid and/or 5-fluorouracil. Collective data of trials evaluating
      cytokine-based therapies for mRCC show an overall response rate of approximately
      15%, with 5% of the patients showing complete responses. More importantly,
      cytokine treatment clearly translates into a significant survival benefit in a
      subset of patients. Nevertheless, the toxicity profile of these cytokine regimens
      is significant. With the enhanced knowledge of tumor-immunology, the
      identification of immunogenic tumor proteins, and antibodies recognizing tumor
      associated antigens, new treatment strategies with increased specificity and
      fewer side effects are of interest. Here we review the different
      immunotherapeutical modalities currently used as well as new approaches for the
      treatment of advanced RCC.

PMID- 12814678
TI  - Thrombospondin-1, vascular endothelial growth factor expression and microvessel
      density in renal cell carcinoma and their relationship with multifocality.
AB  - OBJECTIVE: To evaluate the relevance of microvessel density (MVD) and the
      angiogenic factors, vascular endothelial growth factor (VEGF, an important
      angiogenic factor in solid tumors) and thrombospondin-1 (TSP-1, a potent
      inhibitor of angiogenesis), to multifocality of renal cell carcinoma (RCC).
      PATIENTS AND METHODS: Using immunohistochemistry the expression of CD34, TSP-1
      and VEGF was assessed in 38 archival tissue specimens from 19 patients with
      unifocal RCC and 19 with multifocal RCC. Immunostaining results for VEGF was
      scored for the appropriate percentage of positive tumor cells and relative
      immunostaining intensity (score range 0-12). Only extracellular immunoreactivity
      was considered positive for TSP-1 and the same method was used to score the
      stromal staining. The microvessel density was measured by immunohistochemical
      staining with anti-CD34 monoclonal antibody. RESULTS: VEGF immunoreactivity> or
      =1% was detectable in all unifocal and multifocal tumors. TSP-1 immunoreactivity
      was detected in 14 (73.7%) of 19 unifocal RCCs and in 16 (84.2%) of 19 multifocal
      RCC specimens (p=0.69). There were no statistically significant differences in
      the immunostaining intensity, percentage of immunopositive cells and the staining
      scores of VEGF and TSP-1 among the two groups. Additionally, there was no
      difference in MVD in multifocal and unifocal tumors. CONCLUSION: As there is no
      difference in MVD count, and expression of angiogenic factors (VEGF and TSP-1) in
      multifocal and unifocal tumors, multifocality of RCC is not determined by
      VEGF/TSP-1 expression.

PMID- 12814679
TI  - Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the
      treatment of benign prostatic hyperplasia.
AB  - OBJECTIVE: The objective of this paper is to examine safety and tolerability data
      from a number of recently completed clinical trials with the novel, dual 5alpha
      reductase inhibitor, dutasteride. METHODS: Intent-to-treat analyses were
      conducted on data for dutasteride 0.5 mg/day for drug-related adverse events,
      clinical laboratory test results, and prostate-specific antigen (PSA) levels
      derived from four large, randomised, double-blind clinical trials (n=5655).
      Further data were derived from a randomised, double-blind combination study of
      dutasteride 0.5 mg/day and tamsulosin 0.4 mg/day (n=327), and several safety
      studies conducted in healthy volunteers. RESULTS: Data from two-year blinded
      clinical studies demonstrate that dutasteride is well tolerated, with a profile
      comparable with that of placebo. The exception is a modestly elevated incidence
      of impotence, decreased libido, ejaculation disorders, and gynaecomastia.
      Clinical laboratory test abnormalities were reported by <1% of patients treated
      with dutasteride, and abnormal values occurred with similar frequency versus
      placebo-treated patients. In a healthy volunteer study, when dutasteride was
      administered daily for 1 year, it did not significantly affect bone metabolism
      markers, bone mineral density or lipid profiles. Dutasteride reduced total serum
      PSA concentrations by approximately 50% following 6, 12, and 24 months of
      treatment but had no effect on free-to-total PSA levels. The safety profile of
      dutasteride did not differ from that of finasteride in a large, parallel-group,
      comparator trial. Additionally, when dutasteride was used in combination with an
      alpha(1)-blocker, the drug-related adverse event profiles were as would be
      expected for the individual agents. CONCLUSIONS: Considered together, these data
      demonstrate dutasteride to be well-tolerated.

PMID- 12814680
TI  - Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for
      treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to
      five years from three centers.
AB  - OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH.
      However the major criticism, as with all alternative treatments for BPH, was the
      lack of long-term data. We present the clinical outcome of patients treated by
      TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic
      BPH treated with TUNA were followed for five years in three different centers.
      All patients were treated using the TUNA II or TUNA III catheters under local
      anesthesia only without general or spinal anesthesia. Baseline and 5-year follow
      up evaluation included urinary peak flow, International Prostate Symptom Score
      (IPSS) and post-void residual urine (PVR). The number of patients requiring
      additional medical or surgical treatment was recorded. Statistics were performed
      using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak
      flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR
      decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t
      test). The percentage of patients who improved by at least 50% their peak uroflow
      and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did
      not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively
      at 5 years, both p values > 0.05, t-test). Two patients died of unrelated
      comorbidities and 10 were lost for follow-up. Medical treatment was given to 12
      patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery
      indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and
      10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up
      following the original TUNA procedure. CONCLUSIONS: TUNA is effective and
      provides good long-term clinical improvement at 5-year follow-up. TUNA treatment
      stands the test of time at 5-year follow-up with low and acceptable failure
      rates. More than 75% of the patients do not need additional treatment for BPH on
      the long run.

PMID- 12814681
TI  - Identification of baseline clinical factors which predict medical treatment
      failure of benign prostatic hyperplasia: an observational cohort study.
AB  - OBJECTIVE: The aim of this study was to identify the clinical baseline factors
      that affect the long-term treatment failure of benign prostatic hyperplasia
      (BPH). METHODS: 437 men over 50 years of age with BPH were enrolled for this
      analysis. Patients were allocated to a medication and a surgical treatment
      (following medication) group. We initially examined the International Prostatic
      Symptom Score (IPSS), uroflow rate, prostate volume, postvoid residual volume,
      and the serum prostate specific antigen level as clinical baseline factors and
      analyzed differences between the two groups. RESULTS: 337 patients (77.1%) were
      given maintenance medical treatment during follow-up, and 100 patients (22.9%)
      had surgical treatment following medication. Statistically significant
      differences were found in IPSS and prostate volume between the surgical and
      medication groups (IPSS: 22.6+/-6.4 vs. 18.7+/-5.8, prostate volume (cm(3)):
      36.3+/-14.4 vs. 30.1+/-11.0, respectively). According to the ROC curve-based
      prediction of the failure for medical therapy, the best cutoff values of IPSS and
      prostate volume were 21 (area under ROC curve: 0.67) and 32cm(3) (area under ROC
      curve: 0.65), respectively. CONCLUSIONS: The results show that BPH patients with
      more severe IPSS and larger prostate volume have a higher risk of medical
      treatment failure, and suggest that the IPSS and prostate volume may be useful
      predictors of medical treatment maintenance.

PMID- 12814682
TI  - Prostatic tissual distribution of alfuzosin in patients with benign prostatic
      hyperplasia following repeated oral administration.
AB  - OBJECTIVES: The blood and prostatic concentrations of alfuzosin were determined
      in patients with benign prostatic hyperplasia (BPH). METHODS: 12 patients
      scheduled for BPH surgery were treated with alfuzosin 5 mg twice daily prior to
      surgery in an open trial. Seven doses were given over a 4-day period. Blood
      samples were drawn before the first and the last intake (day 3). On day 4
      (surgery day), a blood and prostate tissue sample were taken simultaneously 12
      hours after the last drug intake. RESULTS: Mean trough blood levels were 6.0+/
      4.6 ng/ml and 5.8+/-3.7 ng/ml on day 3 and day 4, respectively, indicating a
      stable alfuzosin concentration. The mean prostate concentration on day 4 was
      12.3+/-5.6 ng/g. Alfuzosin prostate and blood concentrations at 12 hours post
      dosing on day 4 were significantly correlated (r=0.804, p=0.0016); the prostate
      blood ratio was 2.4+/-0.7. CONCLUSIONS: Oral administration of alfuzosin leads to
      a high diffusion of the drug into the prostate of BPH patients.

PMID- 12814683
TI  - Non-inflammatory chronic pelvic pain syndrome can be caused by bladder neck
      hypertrophy.
AB  - PURPOSE: Little is known about the etiology of the non-inflammatory Chronic
      Pelvic Pain Syndrome (CPPS, NIH category IIIb). We conducted this study to
      determine whether endoscopic and urodynamic evaluation provide objectively
      measurable parameters that may support the rationale of therapeutic strategies
      for patients who failed to respond to medical treatment of non-inflammatory CPPS.
      MATERIALS AND METHODS: The 48 patients included in this study fulfilled the NIH
      criteria for non-inflammatory chronic pelvic pain syndrome category IIIb. All
      patients had received multiple courses of antimicrobial and/or anti-inflammatory
      drugs, but suffered recurrent symptoms. An endoscopic and urodynamic evaluation
      was performed after any medical treatment had been discontinued for at least 6
      weeks. RESULTS: At urethrocystoscopy, no patient had endoscopic evidence of
      obstruction due to urethral stricture, but 29 patients (60%) were found to have
      significant bladder neck hypertrophy. At urodynamic evaluation, these 29 patients
      had an increased detrusor opening pressure DOP (49 vs. 29 cmH(2)O), an increased
      detrusor pressure at maximal flow P(det,Q(max)) (55 vs. 34 cmH(2)O), a decreased
      maximal flow Q(max) (10 vs. 17 ml/s) and an increased postvoid residual urine PVR
      (67 vs. 17 ml) when compared to the 19 patients with a normal appearing bladder
      neck. These differences were statistically significant (p<0.05). When assessed
      with the NIH Chronic Prostatitis Symptom Index (CPSI) the two groups showed no
      difference in the domains of pain and quality of life impact but urinary symptoms
      were significantly more pronounced in the presence of bladder neck alterations.
      CONCLUSIONS: Patients with non-inflammatory CPPS who fail to respond to medical
      treatment with antibiotics and/or anti-inflammatory drugs may have morphological
      alterations in form of bladder neck hypertrophy. This can be suspected when
      urinary symptoms, residual urine and decreased Q(max) are present. These can be
      assessed by non-invasive methods. Endoscopic and/or urodynamic evaluation seem to
      be justified in these patients in order to establish the diagnosis, consider
      alpha-adrenergic blockade and avoid unnecessary antibiotic treatment.

PMID- 12814684
TI  - Spontaneous rupture of non-tumoral kidneys in patients with end stage renal
      failure: risks and management.
AB  - OBJECTIVES: To determine the risks and treatment modalities of spontaneous
      subcapsular or perinephric bleeding in end stage renal patients. METHODS: 8
      patients with end stage renal failure developed a spontaneous hemorrhage of one
      of their native kidneys and were referred to our institution. They were all men.
      Six of them presented an acquired renal cystic disease. Symptoms included sudden
      abdominal pain in 7 patients, vomiting in 2 and hematuria in 1. Symptoms were
      always associated with a hemoglobin decrease. Four patients were receiving oral
      anticoagulants for various reasons and one had thrombopenia. Bleeding was
      confirmed by computerized tomography and nephrectomy undertaken in all cases.
      RESULTS: 3 patients died in the immediate post-operative period. Histologic
      findings confirmed bleeding and did not find any other abnormality than those
      related to renal insufficiency (cysts and atrophy). CONCLUSION: Renal rupture
      should be considered in case of unexplained distress or sudden fall of the
      hemoglobin especially when patients are on anticoagulants. Surgery is our
      preferred treatment because of the frequency of unrevealed tumours and the
      potential mortality of massive hematomas.

PMID- 12814685
TI  - Perioperative antibiotic prophylaxis in ureteroscopic stone removal.
AB  - OBJECTIVE: This study shall settle the question whether a perioperative single
      shot prophylaxis in connection with a ureteroscopic stone removal has an
      influence on the rate of postoperative urinary tract infections (UTIs) and
      inflammable complications or not. METHODS: 113 patients were included in this
      prospective randomized study. In 57 patients 250mg Levofloxacin p. o. was given
      approximately 60 prior ureteroscopy, 56 patients had no prophylaxis. The
      evaluation of all data which were processed electronically was carried out with
      the help of a standardised questionnaire. RESULTS: Postoperatively symptomatic
      urinary tract infections or inflammable complications of the urogenital tract
      were found in neither of the two groups. In the group without prophylaxis, the
      rate of the postoperative significant bacteriurias was significantly higher than
      in the group with prophylaxis (7 patients [12.5%] vs. 1 patient [1.8%])
      (p=0.026). In six cases there was an E. coli bacteriuria; additionally a Kl.
      pneumoniae and a not specified Staphylococcus bacteriuria were detected in
      further cases. CONCLUSION: Single shot prophylaxis using 250 mg Levofloxacin p.
      o. can be considered as cheap, the patient not burdened and regarding the missed
      selection pressure to nosocomial pathogens the preferred manner of perioperative
      antibiotic prophylaxis in ureteroscopic stone removal. In addition perioperative
      single shot prophylaxis may be beneficial in case of an unexpected intraoperative
      complication like e.g. ureter perforations.

PMID- 12814686
TI  - Idiopathic partial thrombosis of the corpus cavernosum: conservative management
      is effective and possible.
AB  - Three cases of spontaneous, partial, unilateral thrombosis of the corpus
      cavernosum are described. The patients presented with a painful mass in the
      perineum without priapism. Diagnosis was made through ultrasound evaluation and
      magnetic resonance imaging, showing unilateral, partial thrombosis of the corpus
      cavernosum. Treatment consisted of systemic anticoagulation. In all three cases,
      the thrombosis resolved spontaneously over several months without complications.
      The aetiology of partial thrombosis of the corpus cavernosum remains unclear, but
      conservative management of this rare condition appears to be effective and safe.

PMID- 12814687
TI  - Comparison of ultrasonographic and laparoscopic findings in adult nonpalpable
      testes cases.
AB  - OBJECTIVE: There is a small number of studies in adult nonpalpable testes cases,
      and there is no published paper on the diagnostic value of their ultrasonographic
      examination. In this prospective study, we compared the sonographic and
      laparoscopic findings in adult cases with nonpalpable testes to assess the
      necessity and the profits of ultrasound. MATERIALS AND METHODS: 50 cases, 38
      unilateral and 12 bilateral, with nonpalpable testes were investigated. Patients'
      ages ranged from 20 to 25 years with a mean of 22. Sonographic examinations were
      performed with a high-resolution ultrasonography device. RESULTS: Laparoscopic
      evaluation of the patients with unilateral nonpalpable testis yielded 27 testes
      out of a total 38. In one case, the testis was detected in the inguinal canal
      with inguinal exploration. The remaining 10 cases were regarded as vanishing
      testes. All 24 testes of 12 patients with bilateral nonpalpable testes were
      found. The pre-laparoscopic ultrasonographic examination detected 20 of 24 testes
      in bilateral cases (83% sensitivity), and 17 of 26 testes in unilateral cases
      (65% sensitivity). CONCLUSION: Our results suggest that ultrasonography does not
      exclude the necessity for laparoscopy, and it is not superior to physical
      examination in detection of the inguinal atrophic testes or testicular nubbin.

PMID- 12814688
TI  - Results of the tension-free vaginal tape technique in the elderly.
AB  - OBJECTIVES: To assess the results of the Tension-Free Vaginal Tape (TVT)
      technique for the treatment of stress urinary incontinence (SUI) in the elderly.
      PATIENTS AND METHODS: Between March 1998 and February 2001, 76 consecutive women
      more than 70 years old (median 76) and presenting with SUI were operated with the
      TVT technique. 28.9% (22/76) of the patients had previous surgery for SUI. 31%
      (24/76) of the patients had an overactive bladder and 4 patients had detrusor
      instability controlled by anticholinergic therapy. All patients had preoperative
      multichanel urodynamic evaluation. RESULTS: No serious complication was noted
      intra- or postoperatively. At a mean follow up of 24.6 months (range 16-49
      months), 67% of the patients were cured (51/76). Among the failures, 10 patients
      (13.7%) had persistent SUI, 14 patients (18.4%) had urge incontinence and 2
      patients were lost to follow up. De novo urgency without incontinence was noticed
      in 21% of the patients but preoperative urgency symptoms were cured in 46% of the
      patients. Overall 82% of the patients were satisfied with the result of the
      surgery, 14% considered the result as incomplete and 4% considered they were
      worsened by surgery. CONCLUSION: The TVT procedure is safe and efficient to treat
      SUI in the elderly population even if the rate of de novo urgency appeared to be
      significant.

PMID- 12814689
TI  - Laparoscopic radical cystoprostatectomy: a technique illustrated step by step.
AB  - OBJECTIVES: Laparoscopic surgery is expanding among urologists as a minimally
      invasive treatment and may now be applied to treat neoplasms of the pelvic
      organs. Laparoscopic cystoprostatectomy has still not been well codified and
      illustrated. We describe a technique of laparoscopic radical cystoprostatectomy
      that we have developed in 10 patients after practicing in laparoscopic radical
      prostatectomy. METHODS: Between June 2001 and July 2002, 10 men with bladder
      cancer underwent laparoscopic cystoprostatectomy with urinary diversion. This
      report details step by step our 5-port transperitoneal technique with primary
      access to the seminal vesicles and Denonvillier's fascia, ureters detection after
      umbilical arteries incision, endopelvic fascia incision and dorsal vein complex
      control before division of the vesical and prostatic fibrovascular pedicles with
      a harmonic scalpel. RESULTS: We performed 6 orthotopic ileal neobladders, 2
      sigmoid ureterostomies and 2 cutaneous ureterostomies. In all cases no conversion
      to open surgery was necessary. The mean time to perform the laparoscopic radical
      cystoprostatectomy, including the lymph node dissection, was 166 minutes (range
      150-180). Mean estimated blood loss was 310 ml (range 220-440). Mean hospital
      stay was 8.1 days (range 7-9) for ileal orthotopic neobladder, 8 days (range 7-9)
      for sigmoid ureterostomy and 5 days for cutaneous ureterostomy. The mean follow
      up is 12.3 months (range 5-18). Two patients respectively with stage T2bN0 G2-3
      and stage pT1N0 (plus carcinoma in situ) G3 transitional cell carcinoma and
      surgical margins tumor free had diffusive metastatic disease after 6 months. The
      other 8 patients are free from disease. CONCLUSIONS: Laparoscopic radical
      cystectomy is still an operation for pioneers but this procedure may be not
      strictly relegated to a few academic centers. In our opinion laparoscopic
      cystoprostatectomy is a feasible, fast, safe and easy procedure and urinary
      diversion may be performed with a laparoscopic, open or combined approach without
      reducing the advantages of laparoscopy.

PMID- 12814690
TI  - Botulinum-a toxin detrusor injection as a novel approach in the treatment of
      bladder spasticity in children with neurogenic bladder.
AB  - OBJECTIVES: Children with neurogenic hyper-reflexive bladder in whom classical
      therapy with anticholinergic drugs and intermittent catheterization fails are
      threatened by high intravesical pressure, vesicoureteral reflux, and impairment
      of kidney function. Surgery, such as bladder augmentation, is often necessary in
      such cases. To obviate surgery in these high-risk children, we investigated the
      use of detrusor injection of botulinum-A toxin (Botox). METHODS: Our subjects
      were 20 children with hyper-reflexive detrusor muscle and high bladder pressure,
      over 40 cmH(2)O despite anticholinergic therapy. After baseline urodynamic
      measurements, we injected botulinum-A toxin into the detrusor muscle at 30-50
      sites at 12 U/kg of body weight up to a maximum of 300 U. Follow-up cystometric
      measurements were taken two to four weeks and three and six months after
      injection. RESULTS: From basic measurements to follow-up cystometry, mean reflex
      volume changed from 97.1 ml before injection to 178.6 ml after four weeks
      (p<0.01) and to 162.8 ml after three months (p<0.01). After six months mean
      reflex volume returned to 119.3 ml (n.s.). Maximal bladder capacity changed from
      163.1 ml to 219.9 ml (p<0.01), to 200.6 ml (p<0.01) and to 222.4 ml (p<0.01),
      respectively, and maximal detrusor pressure changed from 59.6 cmH(2)O to 34.9
      cmH(2)O (p<0.01), to 46.7 cmH(2)O (n.s.) and to 61.8 cmH(2)O (n.s.),
      respectively. CONCLUSION: Botulinum-A toxin (Botox) is effective when injected
      into the hyper-reflexive detrusor muscle. It is a valuable treatment option in
      the management of neurogenic bladder. The effect lasts about six months, and then
      reinjection is necessary.

PMID- 12814691
TI  - Epidermal growth factor and monocyte chemotactic peptide-1 expression in reflux
      nephropathy.
AB  - OBJECTIVES: Reflux nephropathy (RN) is recognised as a major cause of end stage
      renal failure in children and young adults. The histological findings of RN are
      tubular atrophy and interstitial monocyte infiltration. Epidermal growth factor
      (EGF) produced by tubular cells playing a pivotal role in the modulation of
      tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful
      and specific chemotactic and activating factor for monocytes. It has been
      suggested that the modulation of local EGF production is directly involved in the
      pathogenesis of tubular damage. We designed this study to investigate the
      expression of EGF and MCP-1 in severe reflux nephropathy in order to further
      understand the pathogenesis of reflux nephropathy. METHODS: The kidney specimens
      from 12 children with severe reflux nephropathy were obtained at the time of
      nephrectomy. Control material included normal kidney specimens obtained from
      three adult patients during partial nephrectomy for an incidentaloma. Single
      label immunofluorescence histochemistry was carried out using polyclonal
      antibodies to EGF and MCP-1 employing laser scanning confocal microscopy. EGF and
      MCP-1 gene expression were evaluated by in situ hybridization (ISH). TUNEL method
      was utilized to assess tubular apoptosis. RESULTS: In the normal kidney there was
      strong EGF immunoreactivity in the proximal tubules compared to the reflux
      nephropathy where there was lack of immunoreactivity in the proximal tubules.
      Normal kidney demonstrated lack of MCP-1 immunoreactivity, whereas reflux
      nephropathy kidney showed strong MCP-1 immunoreactivity in the proximal tubules
      and tubulointerstitial space. In the normal kidney there was marked EGF mRNA
      expression in the proximal tubules whereas EGF mRNA expression was undetectable
      in reflux nephropathy kidney. MCP-1 mRNA expression was undetectable in normal
      kidney, whereas there was strong MCP-1 mRNA expression at the tubulointerstitial
      level in reflux nephropathy kidney. Decreased EGF expression and increased MCP-1
      expression at the tubulointerstitial levels in reflux nephropathy strongly
      correlated with severity of apoptosis in reflux nephropathy compared with
      controls. CONCLUSIONS: Our data suggests that the downregulation of EGF with
      simultaneous upregulation of MCP-1 may be involved in the pathogenesis of
      tubulointerstitial damage in reflux nephropathy.

PMID- 12814692
TI  - Polymorphisms in the vitamin D receptor gene and the risk of calcium
      nephrolithiasis in children.
AB  - OBJECTIVE: Polymorphism in the Vitamin D Receptor (VDR) gene has recently been
      reported to be associated with calcium metabolism disorders. This study was
      conducted to investigate the association of VDR gene polymorphism with the risk
      of calcium nephrolithiasis. METHODS: We investigated the VDR ApaI, BsmI and TaqI
      polymorphisms, in relation to serum calcium, phosphate, intact parathyroid
      hormone and 1.25(OH)(2)D(3) in 64 hypercalciuric stone-forming children and 90
      healthy children. DNA was isolated from peripheral blood, and genotyping was
      performed with PCR-based methods. RESULTS: The frequency of ApaI AA genotype was
      significantly higher in the children with calcium nephrolithiasis than the
      controls (chi(2)=9.5; p=0.008). The distribution of BsmI and TaqI genotypes in
      stone-forming patients was similar to those in the control group. There was a
      significant association between TaqI TT genotype and the strength of the family
      history. The patients with TT genotype were observed to have a 8 times more risk
      than patients with Tt/tt genotype for recurrent stone episodes (OR 8, 95%CI 1.61
      39.6). CONCLUSION: VDR genotype determination may provide a tool to identify
      individuals who are at a risk for calcium nephrolithiasis.

PMID- 12814693
TI  - Kidney transplantation into an ileocecal reservoir after total extirpation of the
      urinary tract for panurothelial cancer: long-term followup.
AB  - We report on the long-term followup of a young woman after total extirpation of
      the urinary tract for panurothelial cancer with subsequent continent urinary
      diversion and renal transplantation. If a patient is willing to accept the
      associated risks, the staged procedure can be a highly satisfactory treatment
      option. Life-long close surveillance is critical for the success of this concept.

PMID- 12814694
TI  - Th1 and Th2 indices of the immune response in pigs vaccinated against Taenia
      solium cysticercosis suggest various host immune strategies against the parasite.
AB  - Kinetics of the production of serum antibody levels and Th1 (IL-2, IFN-gamma) and
      Th2 (IL-4, IL-10) cytokines was studied in five pigs vaccinated with a synthetic
      tri-peptide vaccine (S3Pvac) against Taenia solium, a vaccine that has been shown
      protects pigs against naturally acquired infection. Healthy pigs of mixed genetic
      background, similar to those bred in rural villages of Mexico, were vaccinated
      with S3Pvac or with adjuvant alone, kept in sanitary conditions and bled at
      different times after vaccination to study the development of their specific
      immune response. Peripheral blood mononuclear cells (PBMCs) of vaccinated pigs
      showed a significant increment in the production of Th1 cytokines (IL-2 and IFN
      gamma) but not of Th2 cytokines (IL-4 and IL-10) after specific PBLs stimulation
      with all the individual peptides. A Th1-inclined cytokine profile leading to an
      exacerbated local inflammation at the early installation stage of the cysticercus
      may possibly interfere with their successful establishment in the serum
      antibodies against total cysticercus antigens and against each of the three
      different peptides comprising S3Pvac were detected 7-51 days after vaccination.
      Antibodies against GK-1 interfered with the cysticerci development into
      intestinal tapeworms in prednisolone-treated hamsters. The sub-lethal crippling
      effect of anti-GK-1 antibodies upon cysticerci indicates to a therapeutic
      application of S3Pvac in infected pigs having potential epidemiological
      consequences, as it could aid in decreasing the number of tapeworms expected to
      develop from the few cysticerci that survive in the vaccinated pigs.

PMID- 12814695
TI  - Intestinal exposure to a parasite antigen in utero depresses cellular and
      cytokine responses of the mucosal immune system.
AB  - The response of the mucosal immune system of 4-6-week old lambs to viable
      Trichostrongylus colubriformis larvae was compared in two groups of animals, one
      exposed to T. colubriformis antigen and the other to saline while in utero.
      Exposure to larval antigen two-thirds of the way through gestation resulted in
      significant reduction in the frequency of jejunal goblet cells and of ileal
      eosinophils, CD 1b(+) antigen-presenting cells and CD4(+), CD5(+) and CD8(+)
      cells. However, it resulted in a significant increase in the jejunal CD8(+)
      response to postnatal challenge. The expression of the cytokines TNF-alpha and IL
      1 beta in the ileum, and of jejunal NSE, was significantly reduced by in utero
      exposure, whereas those of jejunal TNF-alpha and ileal TGF-beta were increased.
      The observed changes in cellular and cytokine responses to challenge with viable
      larvae, in those lambs previously exposed in utero, indicated that the intestinal
      mucosal immune system remains susceptible to down-regulation until considerably
      later in foetal development than is the case for other components of the immune
      system.

PMID- 12814696
TI  - Molecular cloning and structural analysis of the porcine homologue to CD97
      antigen.
AB  - CD97 is a member of a novel subfamily of leukocyte proteins that are
      characterized by the presence of tandemly repeated extracellular epidermal growth
      factor (EGF)-like domains and a seven-span transmembrane region, known as EGF
      TM7. We here report the cloning of cDNA encoding the pig homologue of CD97. A pig
      CD97 specific probe was generated by PCR amplification of pig leukocyte cDNA,
      using primers based on consensus regions among the known sequences of mouse and
      human CD97. Screening of a pig aorta smooth muscle cDNA library identified one
      clone containing an open reading frame (ORF) that encoded an 18 amino acid
      putative signal peptide, a 141 amino acid sequence consisting of three EGF
      domains, a mucin-like spacer region of 276 amino acid, containing a G-protein
      coupling motif of 52 amino acids, followed by a 250 amino acid region containing
      seven membrane spanning domains and a 47 amino acid cytoplasmic tail. The amino
      acid sequence of the clone was 75, 67 and 59% homologous to cattle, human and
      mouse CD97 antigen, respectively. Therefore, it was termed pig CD97. Pig CD97
      antigen shares many structural features with human, cattle and mouse CD97. RT-PCR
      analysis of cDNA from different pig cells and tissues showed that CD97 was highly
      expressed in leukocytes and lymph node cells. This is the first report describing
      the identification of a member of the EGF-TM7 family in the pig.

PMID- 12814697
TI  - Quantitative analysis of Fas and Fas ligand mRNAs in a feline T-lymphoid cell
      line after infection with feline immunodeficiency virus and primary peripheral
      blood mononuclear cells obtained from cats infected with the virus.
AB  - Apoptosis is frequently observed in feline lymphocytes in association with feline
      immunodeficiency virus (FIV) infection. In this study, to investigate the
      mechanism of FIV-induced apoptosis, levels of Fas and Fas ligand mRNAs were
      measured by real-time reverse transcription-PCR. In a feline T-lymphoid cell line
      the amounts of Fas ligand mRNA increased along with the induction of apoptosis
      after in vitro infection with FIV. In PBMC collected from 10 cats naturally
      infected with FIV, Fas ligand mRNA levels were significantly higher than those in
      PBMC from five uninfected cats. These results indicate that the increased
      expression of Fas ligand may be involved in the induction of apoptosis of
      lymphocytes in FIV infection.

PMID- 12814698
TI  - Use of a Sindbis virus DNA-based expression vector for induction of protective
      immunity against pseudorabies virus in pigs.
AB  - Injection of plasmid DNA encoding pseudorabies virus (PRV) glycoproteins into pig
      muscle has been shown to result in protective immunity against lethal infection.
      Nevertheless, such DNA vaccines are still less efficient than some attenuated or
      killed live vaccines. One way to increase DNA vaccine efficacy is to improve the
      vectorisation system at the molecular level, thereby enhancing the rate of in
      vivo-produced immunogen protein and consequently specific acquired immunity. The
      present study compared the effectiveness of the protein expression system
      depending on Sindbis virus (SIN) replicase [J. Virol. 70 (1996) 508] with that of
      more classical pcDNA3 plasmid. Pigs were vaccinated twice at 3-week interval with
      a mixture of three pcDNA3 plasmids expressing gB, gC and gD (designated as PRV
      pcDNA3) or a mixture of three SIN plasmids expressing the same glycoproteins (PRV
      pSINCP), and were challenged with a highly virulent PRV strain. The two DNA
      vaccines induced PRV-specific T cell-mediated immune response characterized by
      very low levels of IFN-gamma mRNA in PBMC after in vitro antigen-specific
      stimulation. Very low levels of neutralizing antibodies (NAb) were also obtained
      in sera following DNA injection(s). A second DNA injection did not boost immune
      responses. After a lethal challenge, high levels of IFN-gamma mRNA and high NAb
      response were induced in all DNA-vaccinated pigs, regardless of the vector used.
      Therefore, the two eukaryotic expression systems showed comparable efficacy in
      inducing antiviral immunity and clinical protection against PRV in pigs. This
      suggests that SIN DNA-based vector immunizing potential may differ according to
      antigen and/or host.

PMID- 12814699
TI  - In utero infection with porcine reproductive and respiratory syndrome virus
      modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid
      of surviving piglets.
AB  - It is well known that piglets congenitally infected with porcine reproductive and
      respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning
      mortality due to secondary infections often increases during acute outbreaks of
      PRRS. Therefore, an immunosuppressive effect of in utero infection has been
      suggested. The aim of the present study was to characterise the changes of
      leukocyte populations in piglets surviving in utero infection with PRRSV. A total
      of 27 liveborn uninfected control piglets and 22 piglets infected
      transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of
      age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still
      viremic, whereas PRRSV could not be detected in the six infected piglets examined
      at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic
      composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid
      (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected
      controls. The key observation in the present study is that high levels of CD8(+)
      cells constitute a dominant feature in peripheral blood and BALF of piglets
      surviving in utero infection with PRRSV. In BALF, the average high level of
      CD8(+) cells in 2-week-old infected piglets (33.4 +/- 12.6%) was followed by a
      decline to 7.3 +/- 3.0 and 11.1 +/- 3.0% at 4 and 6 weeks of age. BALF of control
      piglets contained 1.6 +/- 0.9, 2.3 +/- 1.8 and 1.9 +/- 0.5% CD8(+) cells, only.
      In peripheral blood, however, the average number of CD8(+) cells remained at high
      levels in the infected piglets throughout the post-natal experimental period (2.8
      +/- 1.9, 2.9 +/- 1.8 and 3.2 +/- 1.7 x 10(6) CD8(+) cells/ml at 2, 4 and 6 weeks,
      respectively). In the controls, the average levels of CD8(+) cells were 0.9+/
      0.2, 1.9 +/- 1.7 and 1.6 +/- 0.5 x 10(6)/ml, respectively. Furthermore, the
      numbers of CD2(+) , CD4(+)CD8(+) and SLA-classII(+) cells, respectively, in
      peripheral blood, together with the levels of CD2(+) and CD3(+) cells in BALF
      were increased in the infected piglets infected in utero compared to the
      uninfected controls. The kinetic analyses carried out in the present study
      reflect that in utero infection with PRRSV modulates immune cell populations in
      peripheral blood and BALF of surviving piglets. The observed changes are
      characterised by high levels of CD8(+) cells supporting an important role of
      these cells in PRRSV infection. The present results, however, do not support the
      existence of post-natal immunosuppression following in utero infection with
      PRRSV.

PMID- 12814700
TI  - Development of a Staphylococcus aureus vaccine against mastitis in dairy cows.
      II. Field trial.
AB  - A recently described new Staphylococcus aureus vaccine "MASTIVAC I" (Patent no.
      PTC/IL98/00627) against S. aureus udder infection elicited protection against
      experimentally induced infection in cows. In the present paper we describe a
      large-scale vaccination field trial. A total of 452 Israeli Holstein heifers were
      included in the study over two consecutive years. Approximately half of the
      heifers (228) were vaccinated while the others (224) served as a control group.
      Antibody response was detected in all vaccinated animals 4-5 weeks post-primary
      immunization and it was sustained throughout the experimental period (300-330
      days). S. aureus infection could be detected in only 3 out of 228 animals (1.3%)
      in the vaccinated group and in 6 out of 224 (2.7%) in the control group. These
      numbers were too low to be statistically evaluated. However, when somatic cell
      counts (SCC) and milk yields were considered, a significant difference was found
      between the two groups, namely, the vaccinated cows in first and second lactation
      had 42 and 54%, respectively, lower SCCs and milk yields 0.5 kg per day higher
      than the non-vaccinated control cows. These results suggest that the new vaccine
      elicits a non-specific health improvement of the udder in addition to specific
      protection against S. aureus.

PMID- 12814701
TI  - Staphylococcus aureus vaccine against mastitis in dairy cows, composition and
      evaluation of its immunogenicity in a mouse model.
AB  - Bovine mastitis caused by Staphylococcus aureus (S. aureus) is a most important
      infection disease that affects both the quality and the quantity of milk
      production. Antibiotic therapies formulated for intramammary use are generally
      unsuccessful in eliminating existing S. aureus infections. Vaccination is a
      logical approach to the control of S. aureus udder infections. However, to date
      commercially available S. aureus vaccine have shown limited efficacy under field
      conditions, mainly due to the paucity of information regarding relevant antigens
      which will induce a broad spectrum immunization. In the present paper the attempt
      to develop a new vaccine designated MASTIVAC I is described. MASTIVAC I is
      composed of three strains of S. aureus namely: VLVL8407; ZO3984 and BS449 which
      were isolated from clinical and sub-clinical cases of bovine mastitis. A mouse
      model was used to evaluate the S. aureus specific antibody production and
      protection of mice against virulent S. aureus strains. The results obtained
      showed that this vaccine exhibits a broad spectrum of antigenic and immunogenic
      properties that protects mice from homologues and hetrologous S. aureus
      challenge.

PMID- 12814702
TI  - The role of WC1(+) gamma delta T-cells in the delayed-type hypersensitivity (DTH)
      skin-test reaction of Mycobacterium bovis-infected cattle.
AB  - Delayed-type hypersensitivity (DTH) skin-testing with mycobacterial antigens is
      often used as a means of identifying Mycobacterium bovis-infected cattle. Better
      understanding of the cellular basis underlying the DTH reaction is required if
      diagnostic methods are to be improved upon. Previous studies have shown that
      gamma delta T-cells, particularly those bearing the WC1 molecule, are present at
      an early stage of developing DTH responses and that such cells may modulate the
      developing immune response immediately following M. bovis-infection. However,
      their role, if any, in the DTH response remains unclear. In the present study we
      have used an in vivo model to deplete WC1(+) gamma delta T-cells, from cattle
      with established M. bovis-infection, prior to skin-testing. Results indicate
      that, although WC1(+) gamma delta T-cells do infiltrate the skin-test site in
      normal calves, they do not appear to be essential for the development of DTH skin
      swelling, as indicated by effective development of skin responses in calves
      depleted of circulating WC1(+) gamma delta T-cells.

PMID- 12814703
TI  - In silico identification of components of the Toll-like receptor (TLR) signaling
      pathway in clustered chicken expressed sequence tags (ESTs).
AB  - We have described a bioinformatic approach that involves the clustering of
      expressed sequence tags (ESTs) to reveal homologs of the Toll-like receptor (TLR)
      pathway in the chicken. Homology searching of proteins, predicted to be encoded
      by these EST clusters, resulted in the in silico identification of full-length
      sequences for Toll-interacting protein (Tollip), IL-1 receptor-associated kinase
      4 (IRAK-4), myeloid differentiation factor 88 adapter-like (Mal), TGF beta
      activated kinase 1 binding protein 1 (TAB1). We also determined partial sequence
      information for myeloid differentiation factor 88 (MyD88), two novel TLRs, TNF
      receptor-associated factor 6 (TRAF6), TGF beta-activated kinase 1 (TAK1), TAB2,
      inhibitor of nuclear factor kappa B kinase alpha (IKK alpha) and IKK beta. This
      bioinformatics study has confirmed the evolutionary conservation of the TLR
      pathway in chicken and demonstrated its essential homology to the TLR pathway in
      mammals. We have identified in silico the full-length sequence for liver
      expressed antimicrobial peptide 2 (LEAP-2). This is the first time a non
      mammalian LEAP-2 has been described.

PMID- 12814704
TI  - SSRIs: suicide risk and withdrawal.

PMID- 12814705
TI  - Major benefits from cholesterol-lowering in patients with diabetes.

PMID- 12814706
TI  - Surgery in the obese.

PMID- 12814707
TI  - SARS genome patent: symptom or disease?

PMID- 12814708
TI  - Sex, lies, and medical compliance.

PMID- 12814709
TI  - Monkeying with Shakespeare.

PMID- 12814710
TI  - MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963
      people with diabetes: a randomised placebo-controlled trial.
AB  - BACKGROUND: Individuals with diabetes are at increased risk of cardiovascular
      morbidity and mortality, although typically their plasma concentrations of LDL
      cholesterol are similar to those in the general population. Previous evidence
      about the effects of lowering cholesterol in people with diabetes has been
      limited, and most diabetic patients do not currently receive cholesterol-lowering
      therapy despite their increased risk. METHODS: 5963 UK adults (aged 40-80 years)
      known to have diabetes, and an additional 14573 with occlusive arterial disease
      (but no diagnosed diabetes), were randomly allocated to receive 40 mg simvastatin
      daily or matching placebo. Prespecified analyses in these prior disease
      subcategories, and other relevant subcategories, were of first major coronary
      event (ie, non-fatal myocardial infarction or coronary death) and of first major
      vascular event (ie, major coronary event, stroke or revascularisation). Analyses
      were also conducted of subsequent vascular events during the scheduled treatment
      period. Comparisons are of all simvastatin-allocated versus all placebo-allocated
      participants (ie, intention to treat), which yielded an average difference in LDL
      cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period.
      FINDINGS: Both among the participants who presented with diabetes and among those
      who did not, there were highly significant reductions of about a quarter in the
      first event rate for major coronary events, for strokes, and for
      revascularisations. For the first occurrence of any of these major vascular
      events among participants with diabetes, there was a definite 22% (95% CI 13-30)
      reduction in the event rate (601 [20.2%] simvastatin-allocated vs 748 [25.1%]
      placebo-allocated, p<0.0001), which was similar to that among the other high-risk
      individuals studied. There were also highly significant reductions of 33% (95% CI
      17-46, p=0.0003) among the 2912 diabetic participants who did not have any
      diagnosed occlusive arterial disease at entry, and of 27% (95% CI 13-40,
      p=0.0007) among the 2426 diabetic participants whose pretreatment LDL cholesterol
      concentration was below 3.0 mmol/L (116 mg/dL). The proportional reduction in
      risk was also about a quarter among various other subcategories of diabetic
      patient studied, including: those with different duration, type, or control of
      diabetes; those aged over 65 years at entry or with hypertension; and those with
      total cholesterol below 5.0 mmol/L (193 mg/dL). In addition, among participants
      who had a first major vascular event following randomisation, allocation to
      simvastatin reduced the rate of subsequent events during the scheduled treatment
      period. INTERPRETATION: The present study provides direct evidence that
      cholesterol-lowering therapy is beneficial for people with diabetes even if they
      do not already have manifest coronary disease or high cholesterol concentrations.
      Allocation to 40 mg simvastatin daily reduced the rate of first major vascular
      events by about a quarter in a wide range of diabetic patients studied. After
      making allowance for non-compliance, actual use of this statin regimen would
      probably reduce these rates by about a third. For example, among the type of
      diabetic patient studied without occlusive arterial disease, 5 years of treatment
      would be expected to prevent about 45 people per 1000 from having at least one
      major vascular event (and, among these 45 people, to prevent about 70 first or
      subsequent events during this treatment period). Statin therapy should now be
      considered routinely for all diabetic patients at sufficiently high risk of major
      vascular events, irrespective of their initial cholesterol concentrations.

PMID- 12814711
TI  - Use of antioxidant vitamins for the prevention of cardiovascular disease: meta
      analysis of randomised trials.
AB  - INTRODUCTION: Oxidised LDL is thought to play an important part in the
      pathogenesis of atherosclerosis. Observational studies have associated alpha
      tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular
      events, but not clinical trials. We did a meta-analysis to assess the effect of
      these compounds on long-term cardiovascular mortality and morbidity. METHODS: We
      analysed seven randomised trials of vitamin E treatment and, separately, eight of
      beta carotene treatment; all trials included 1000 or more patients. The dose
      range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up
      ranged from 1.4 to 12.0 years. FINDINGS: The vitamin E trials involved a total of
      81788 patients and the beta carotene trials 138113 in the all-cause mortality
      analyses. Vitamin E did not provide benefit in mortality compared with control
      treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or
      significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or
      cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but
      significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11]
      p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1
      [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis.
      INTERPRETATION: The lack of a salutary effect was seen consistently for various
      doses of vitamins in diverse populations. Our results, combined with the lack of
      mechanistic data for efficacy of vitamin E, do not support the routine use of
      vitamin E.

PMID- 12814712
TI  - Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a
      multicentre, randomised, placebo-controlled trial.
AB  - BACKGROUND: Renal transplant recipients are at increased risk of premature
      cardiovascular disease. Although statins reduce cardiovascular risk in the
      general population, their efficacy and safety in renal transplant recipients have
      not been established. We investigated the effects of fluvastatin on cardiac and
      renal endpoints in this population. METHODS: We did a multicentre, randomised,
      double-blind, placebo-controlled trial in 2102 renal transplant recipients with
      total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin
      (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary
      endpoint was the occurrence of a major adverse cardiac event, defined as cardiac
      death, non-fatal myocardial infarction (MI), or coronary intervention procedure.
      Secondary endpoints were individual cardiac events, combined cardiac death or non
      fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality,
      and graft loss or doubling of serum creatinine. Analysis was by intention to
      treat. FINDINGS: After a mean follow-up of 5.1 years, fluvastatin lowered LDL
      cholesterol concentrations by 32%. Risk reduction with fluvastatin for the
      primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not
      significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104,
      0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group.
      Coronary intervention procedures and other secondary endpoints did not differ
      significantly between groups. INTERPRETATION: Although cardiac deaths and non
      fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of
      coronary intervention procedures or mortality. Overall effects of fluvastatin
      were similar to those of statins in other populations.

PMID- 12814714
TI  - Obesity in general elective surgery.
AB  - BACKGROUND: Obese patients are generally believed to be at a higher risk for
      surgery than those who are not obese, although convincing data are lacking.
      METHODS: We prospectively investigated a cohort of 6336 patients undergoing
      general elective surgery at our institution to assess whether obesity affects the
      outcome of surgery. Exclusion criteria were emergency, vascular, thoracic, and
      bariatric operations; transplantation procedures; patients under
      immunosuppression; and operations done under local anaesthesia. Postoperative
      morbidity was analysed for non-obese and obese patients (body-mass index <30
      kg/m(2) vs >or=30 kg/m(2)). Obesity was further stratified into mild obesity
      (30.0-34.9 kg/m(2)) and severe obesity (>or=35 kg/m(2)). Risk factors were
      analysed with univariate and multivariate models. FINDINGS: The cohort consisted
      of 6336 patients, of whom 808 (13%) were obese, 569 (9%) were mildly obese, and
      239 (4%) had severe obesity. The morbidity rates in patients who were obese
      compared with those who were not were much the same (122 [15.1%] of 808 vs 901
      [16.3%] of 5528; p=0.26), with the exception of an increased incidence of wound
      infections after open surgery in patients who were obese (17 [4%] of 431 vs 92
      [3%] of 3555, p=0.03). Incidence of complications did not differ between patients
      who were mildly obese (91 [16.0%] of 569), severely obese (36 [15.1%] of 239),
      and non-obese (901 [16.3%] of 5528; p=0.19). In multivariate regression analyses,
      obesity was not a risk factor for development of postoperative complications. Of
      note, the additional medical resource use as estimated by a new classification of
      complications showed no differences between patients who were and were not obese.
      INTERPRETATION: Obesity alone is not a risk factor for postoperative
      complications. The regressive attitude towards general surgery in obese patients
      is no longer justified.

PMID- 12814715
TI  - TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for
      interferon-beta treatment in multiple sclerosis.
AB  - BACKGROUND: Many patients with multiple sclerosis do not respond to interferon
      beta, which is widely used as an immunomodulatory treatment in this disease. We
      aimed to assess the functional relevance of tumour necrosis factor (TNF)-related
      apoptosis inducing ligand (TRAIL), which is upregulated on incubation with
      interferon beta, for clinical treatment response. METHODS: We quantified gene
      expression longitudinally by realtime-PCR of the peripheral immune cells of 82
      patients with multiple sclerosis. In a first cohort of 62 patients, 20 were
      classified as first-year responders since they did not have relapses during
      treatment with interferon beta 1a; 19 were classified as first-year non
      responders; and 23 developed neutralising antibodies to interferon beta. A second
      cohort, also characterised by MRI, consisted of 11 patients on interferon beta 1a
      and nine patients who were not treated. Concentrations of soluble TRAIL were
      determined by ELISA in serum samples of nine non-treated patients, 49 patients
      before treatment (29 responders, 20 non-responders), as well as longitudinally in
      a subset of 23 patients. FINDINGS: In both patient cohorts, drug-responders could
      be distinguished from non-responders by early and sustained induction of TRAIL
      (p<0.0001, each). In the presence of neutralising antibodies, initial
      upregulation of TRAIL expression was subsequently abrogated. Raised
      concentrations of soluble TRAIL in patients' serum samples before the start of
      treatment allowed prediction of the treatment response in the first year (ROC
      analysis with area under the curve 0.879 [0.785-0.974]). INTERPRETATION: Our data
      suggest that TRAIL expression is a candidate for pretreatment assessment and
      might thus be used as a prognostic marker of treatment response to interferon
      beta in multiple sclerosis. Furthermore, our observations have implications for
      the development of future immunoregulatory strategies in multiple sclerosis
      therapy.

PMID- 12814716
TI  - Bilateral retinal detachment in a young woman.

PMID- 12814717
TI  - Glycyrrhizin, an active component of liquorice roots, and replication of SARS
      associated coronavirus.
AB  - The outbreak of SARS warrants the search for antiviral compounds to treat the
      disease. At present, no specific treatment has been identified for SARS
      associated coronavirus infection. We assessed the antiviral potential of
      ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against
      two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS
      admitted to the clinical centre of Frankfurt University, Germany. Of all the
      compounds, glycyrrhizin was the most active in inhibiting replication of the SARS
      associated virus. Our findings suggest that glycyrrhizin should be assessed for
      treatment of SARS.

PMID- 12814718
TI  - Progression of cerebral white matter lesions: 6-year results of the Austrian
      Stroke Prevention Study.
AB  - More than half of all elderly people have some degree of cerebral white matter
      lesions. However, the rate of progression of these lesions is uncertain. We aimed
      to assess the progression of lesions in community-dwelling volunteers aged 50-75
      years without neuropsychiatric disease. We used MRI to grade and measure the
      total volume of white matter lesions in 296 volunteers at baseline, 3 years, and
      6 years. 58 participants with no lesions and 123 with punctate abnormalities at
      baseline had a low tendency for lesion progression, whereas 14 participants with
      early confluent and nine with confluent lesions underwent median increases of 2.7
      cm(3) (IQR 0.5-5.9) and 9.3 cm(3) (7.1-21.0), respectively, in lesion volume at 6
      years. Lesion grade at baseline was the only significant predictor of lesion
      progression (p<0.0001). Punctate white matter lesions are not progressive and are
      thus benign, whereas early confluent and confluent white matter abnormalities are
      progressive, and thus malignant.

PMID- 12814719
TI  - Effect of moderate anaemia on later mortality in rural African children.
AB  - Severe anaemia in childhood is associated with increased mortality, although
      evidence relating moderate anaemia to child survival is scarce. We aimed to
      investigate this association. We did a case-control study of children with
      moderate anaemia, and compared haemoglobin concentrations measured up to a year
      before death for 403 children (age range 28 days to 15 years) with those from
      children who survived (matched for age and sex). Data were obtained from long
      term health records (1950-97) of a rural Gambian research centre. Excluding an
      acute effect in this last week of life, no evidence was recorded of lower
      haemoglobin concentrations in the children who died than in survivors, or of any
      general or disease-specific effects of non-severe anaemia (70-110 g/L) on
      mortality.

PMID- 12814720
TI  - UK ethicists say GM foods could help poor. Group back the controversial crops as
      government warily tests public opinion.

PMID- 12814722
TI  - Why do men and women feel and react to pain differently? Research suggests men
      and women may not process pain signals the same way.

PMID- 12814723
TI  - Edmonton's islet success tough to duplicate elsewhere.

PMID- 12814725
TI  - Scientists report progress against non-small cell lung cancer.

PMID- 12814726
TI  - UN warns Asia-Pacific may not meet millennium health targets.

PMID- 12814727
TI  - European Union scrambles to revise drug approval laws.

PMID- 12814729
TI  - Government forced to put doctors under the spotlight. Calls for transparency
      prompt Japanese doctors to reexamine the way they practise medicine.

PMID- 12814730
TI  - von Hippel-Lindau disease.
AB  - von Hippel-Lindau disease is a heritable multisystem cancer syndrome that is
      associated with a germline mutation of the VHL tumour suppressor gene on the
      short arm of chromosome 3. This disorder is not rare (about one in 36000
      livebirths) and is inherited as a highly penetrant autosomal dominant trait (ie,
      with a high individual risk of disease). Affected individuals are at risk of
      developing various benign and malignant tumours of the central nervous system,
      kidneys, adrenal glands, pancreas, and reproductive adnexal organs. Because of
      the complexities associated with management of the various types of tumours in
      this disease, treatment is multidisciplinary. We present an overview of the
      clinical aspects, management, and treatment options for von Hippel-Lindau
      disease.

PMID- 12814732
TI  - Group practice.

PMID- 12814731
TI  - Nosocomial infections in adult intensive-care units.
AB  - Nosocomial infections affect about 30% of patients in intensive-care units and
      are associated with substantial morbidity and mortality. Several risk factors
      have been identified, including the use of catheters and other invasive
      equipment, and certain groups of patients-eg, those with trauma or burns-are
      recognised as being more susceptible to nosocomial infection than others.
      Awareness of these factors and adherence to simple preventive measures, such as
      adequate hand hygiene, can limit the burden of disease. Management of nosocomial
      infection relies on adequate and appropriate antibiotic therapy, which should be
      selected after discussion with infectious-disease specialists and adapted as
      microbiological data become available.

PMID- 12814733
TI  - Raynaud's disease.

PMID- 12814734
TI  - Severe acute respiratory syndrome coronavirus and viral mimicry.

PMID- 12814735
TI  - Diagnosis of tuberculosis.

PMID- 12814736
TI  - Diagnosis of tuberculosis.

PMID- 12814737
TI  - Diagnosis of tuberculosis.

PMID- 12814739
TI  - Diagnosis of tuberculosis.

PMID- 12814740
TI  - West Nile virus and blood donors.

PMID- 12814741
TI  - Frozen blood.

PMID- 12814742
TI  - Cost of medical education in the USA.

PMID- 12814743
TI  - Syndromic STI and behaviour-change interventions in Uganda.

PMID- 12814744
TI  - Syndromic STI and behaviour-change interventions in Uganda.

PMID- 12814745
TI  - Syndromic STI and behaviour-change interventions in Uganda.

PMID- 12814746
TI  - Roth spots obscure the picture.

PMID- 12814748
TI  - How international are psychiatry journals?

PMID- 12814749
TI  - Acute myocardial infarction.

PMID- 12814750
TI  - Acute myocardial infarction.

PMID- 12814752
TI  - Acute myocardial infarction.

PMID- 12814751
TI  - Management of severe malnutrition: facilitating learning.

PMID- 12814757
TI  - Synergistic effect of vitamin D and calcium in preventing proximal femoral
      fractures in older patients.

PMID- 12814758
TI  - Antisynthetase syndrome.
AB  - Seven autoantibodies directed against synthetases have been identified to date,
      the best known being anti-Jo1. Synthetases play a vital role in protein synthesis
      by catalyzing the acetylation of transfer RNAs (tRNAs). The most common form of
      antisynthetase syndrome is characterized by anti-Jo1 production, interstitial
      lung disease (ILD), inflammatory muscle disease, and, in many cases, fever,
      polyarthritis, Raynaud's phenomenon, and thick cracked skin on the fingers
      (mechanic's hands). The interstitial lung disease is generally of the "usual
      interstitial pneumopathy" type and shares similarities with idiopathic pulmonary
      fibrosis or scleroderma-related pulmonary disease. It governs the prognosis of
      the disease, being associated with an excess mortality rate of about 40%. The
      pathogenic mechanisms underlying antisynthetase syndrome remain unknown but may
      involve cell-mediated immunity. The treatment is not standardized. The ILD
      responds to glucocorticoids in some patients but requires other immunosuppressant
      drugs in others.

PMID- 12814759
TI  - Antibiotic-loaded bone cement in orthopedic surgery.
AB  - Acrylic cement is used to secure implants to bone. When mixed with antibiotics or
      anticancer agents, acrylic cement slowly releases these agents while retaining
      its mechanical properties, thus providing specific in situ treatment.

PMID- 12814760
TI  - Treatment of multiple myeloma.
AB  - Conventional chemotherapies are no longer the only treatment in multiple
      myelomatosis. High-dose chemotherapy and autologous transplantation are not
      curative but do increase relapse-free survival time in young patients.
      Thalidomide is efficacious in refractory and relapsing myeloma and its evaluation
      is going on. Curative and preventive treatments of skeletal events, infections
      and anemia improve quality of life. All together, these strategies imply
      therapeutic knowledge and choices but allow an about 5-year-long median survival
      time in modern studies. Treatment options for myeloma now include, not only
      conventional chemotherapy regimens, but also novel symptomatic drugs and
      strategies that increase survival and/or quality of life, although they fail to
      provide a cure. In parallel with this expansion of the treatment armamentarium,
      physicians must acquire the knowledge needed to select the best treatment for the
      individual patient. After reviewing the rationale, effectiveness, and safety of
      each of these treatments, we will discuss the indications that we believe are
      legitimate.

PMID- 12814761
TI  - Antinuclear antibodies recognize cellular autoantigens driven by apoptosis.
AB  - OBJECTIVE: Present study addresses the issue whether cellular antigens recognised
      by antinuclear autoantibodies are driven by apoptosis. MATERIALS AND METHODS: HEp
      2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL
      and Bax expression monitored apoptosis. Autoantigens were probed by indirect
      immunofluorescence and Western blot with autoantibodies or monoclonals against:
      DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase I, Jo-1 and NuMA. A comparison
      of antinuclear antibody reactivity between living and apoptotic cells was
      performed by ELISA. RESULTS: Apoptotic changes such as chromatin fragmentation,
      blebs and apoptotic bodies were induced with 20 mM camptothecin. Autoantigens
      were better detected in apoptotic cells. U1-RNP, Jo1, DNA-Topoisomerase I, CENP-B
      and NuMA exhibited fragmentation and redistribution as a consequence of
      apoptosis; in contrast, Ro60 and La ribonucleoproteins did not show proteolysis.
      Additionally the ELISA titers of antinuclear antibodies were higher in apoptotic
      cells than in normal cells. CONCLUSION: Apoptosis induces molecular changes in
      different autoantigens, this modification increases the antigen-driven response
      of autoantibodies such as anti-RNP, anti-DNA Topoisomerase I, anti-CENP-B and
      anti-Jo1. Apoptotic changes would contribute to break down the tolerance in
      autoimmune connective tissue disease.

PMID- 12814762
TI  - Cross-cultural adaptation and validation of an Arabic Health Assessment
      Questionnaire for use in rheumatoid arthritis patients.
AB  - OBJECTIVE: To test the reliability and validity of a modified and translated
      version of the original Health Assessment Questionnaire (HAQ) on patients with
      rheumatoid arthritis (RA). METHOD: A cohort of 184 RA patients from different
      Arabic countries (Egypt, Saudi Arabia, Sudan, Syria, Bahrain, Kuwait and Morocco)
      were recruited and asked to participate in the study. Two questions had been
      changed to suit the Arabic culture and to tackle some aspects that are commoner
      to be performed in the Arabic culture. After modification, translation and
      retranslation of the questionnaire, it was administered to the selected patients
      and tested for internal consistency, reliability and construct validity by
      correlating the yield of the questionnaire with other disease activity
      parameters. The questionnaire was administered again after a 1-week interval for
      evaluation of the reliability of this test. The modified questions were tested
      for their loyalty to the principal component and comparing their correlation with
      that of the other unchanged items. RESULTS: Test-retest showed strong reliability
      with a high percentage of agreement and high values for Kappa. Internal
      consistency showed a high value for standardized alpha (Cronbach's): 0.979 that
      did not show any significant change if any of the 20 items had been eliminated.
      The modified questionnaire had shown a strong validity when correlating its
      results with other disease activity parameters. This correlation was the
      strongest with tender joint count (TJC), Ritchie articular index (RAI), morning
      stiffness (MS) and visual analogue scale (VAS) and the least (but still
      significant) with rheumatoid factor (RF). CONCLUSION: The Arabic HAQ is a
      reliable and valid instrument that can be self-administered to Arabic RA patients
      to evaluate their functional disability. Its measurement properties were
      comparable to versions in other languages.

PMID- 12814763
TI  - Effects on bone mineral density of calcium and vitamin D supplementation in
      elderly women with vitamin D deficiency.
AB  - OBJECTIVE: Calcium and vitamin D deficiency is common in older individuals,
      particularly those who live in nursing homes, and increases the risk of
      osteoporosis and fractures. METHODS: We conducted a randomized double-blind
      placebo-controlled study of combined supplementation with 500 mg of elemental
      calcium, as carbonate, and 400 IU of vitamin D bid for 12 months in women older
      than 65 years of age with vitamin D deficiency, defined as serum 25(OH)D
      concentrations </=12 ng/ml. RESULTS: Mean patient age was 75 +/- 7 years, and
      median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in
      the supplemented group (n = 95) and 671 mg and 61.8 IU in the placebo group (n =
      97). The median serum 25(OH)D level was 7.0 ng/ml in both groups, and the medial
      intact parathyroid hormone (PTHi) levels were 49 and 48 pg/ml in the supplemented
      and placebo groups, respectively. The median increase in serum 25(OH)D was 22.0
      ng/ml in the supplemented group and 4 ng/ml in the placebo group (P < 0.0001),
      and the median PTHi decrease was 17 and 5 pg/ml, respectively (P < 0.0001). The
      median bone mineral density increase was significantly greater in the
      supplemented group than in the placebo group: +2.98% vs. -0.21% at L2-L4 (P =
      0.0009), +1.19% and -0.83% at the femoral neck (P = 0.015), +0.86% and -0.56% at
      the trochanter (P = 0.015), and +0.99% and +0.11% for the whole body (P = 0.01).
      Similarly, the median decrease in the main bone markers was significantly greater
      in the treated group than in the placebo group: -1.35 microg/l vs. +0.50 microg/l
      for bone alkaline phosphatase (P = 0.008), -16.6 nmol/mmol creatinine vs. -2.3
      nmol/mmol creatinine for urinary type I amino-terminal telopeptide (P = 0.001),
      and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide (P
      = 0.003). We found no significant differences between the two groups for serum
      calcium, although urinary calcium excretion changed more in the supplemented
      group than in the placebo group. In conclusion, bone mass in older women with
      vitamin D deficiency increases significantly at the lumbar spine, femur,
      trochanter, and whole body after calcium and vitamin D supplementation for 1
      year, and concomitantly bone markers improved as vitamin D levels returned to
      normal.

PMID- 12814764
TI  - Insufficiency fracture. A survey of 60 cases and review of the literature.
AB  - We report findings on the site, risk factors and imaging of insufficiency
      fractures (IF) in 60 patients admitted to our department between 1989 and 1997.
      RESULTS: Fifty-five women (mean age 72.5 years) and five men (mean age 59 years)
      had 91 fractures, accounting for 0.32% of admissions. Fractures occurred most
      commonly in the pelvic girdle (30.7%, 28/91) and in the sacrum (29.6%, 27/91). In
      eight patients fractures of the sacrum were associated with fractures of the
      pelvic girdle. The next most common sites of occurrence were the tibia (16.5%,
      15/91: 11 transverse, four longitudinal) and the femoral neck (9.9%, 9/91). There
      were three subchondral fractures of the femoral head, three fractures of the
      femoral diaphysis (two longitudinal, one transversal), two of the astragalus, and
      one each of the ilium, perone, calcaneum and sternum. Thirty patients had
      osteoporosis: six had received fluoride treatment and five had corticosteroids.
      Other risk factors were rheumatoid arthritis (4), osteomalacia (4),
      corticosteroid treatment (4), and hyperparathyroidism (1). Radiography showed a
      fracture line or osteocondensation in 65% (39/60) of cases. Scintigraphy was
      positive in 87.5% of cases (21/24), showing a fracture line (15) or a callus (6).
      Bone computed tomography (CT) scan was positive in 98.1% (54/55) of cases. IF
      occurs in elderly women with osteoporosis and most commonly in the pelvis.
      CONCLUSIONS: Since radiologic signs are inconstant, scintigraphy is the choice
      procedure.

PMID- 12814765
TI  - Naturalistic survey on nonsteroidal antiinflammatory treatment in patients with
      musculoskeletal pain.
AB  - OBJECTIVE AND METHODS: To evaluate patients' opinions about the gastrointestinal
      safety and areas for improvement of conventional nonsteroidal antiinflammatory
      drug (NSAID) therapy for musculoskeletal pain, the Louis Harris Institute
      conducted a survey in 401 patients selected in France using a quota sampling
      method. RESULTS: Three hundred and five patients (76%) described their pain as
      incapacitating. Nearly, one-third of the patients (125/401, 31%) reported
      gastrointestinal side effects, which prompted endoscopy in 24 (24/125, 20%) and
      gastroprotective drug treatment (usually by a proton pump inhibitor) in 100
      (100/125, 82%). NSAID discontinuation or dosage reduction because of
      gastrointestinal side effects occurred in 55 patients (55/125, 45%), at the cost
      of symptom exacerbation, including worse pain, in over half the cases. Among the
      401 patients, 304 (76%) wanted more effective NSAIDs and 174 (43%) wanted better
      gastrointestinal tolerability. CONCLUSION: Under everyday conditions, the use and
      effectiveness of conventional NSAID therapy are limited by gastrointestinal side
      effects. Furthermore, patients want NSAIDs with better risk/benefit ratios to
      control musculoskeletal pain.

PMID- 12814766
TI  - Late-onset spondyloarthropathy mimicking reflex sympathetic dystrophy syndrome.
AB  - Atypical presentations are common when spondyloarthropathy develops in older
      patients. We report two cases initially mistaken for reflex sympathetic dystrophy
      syndrome (RSDS). Both the patients were men, aged 62 and 75 years, respectively,
      with marked painful edema of a foot. One patient reported a moderate-energy
      trauma as the triggering event. Severe diffuse demineralization was noted on
      radiographs and diffuse hyperactivity on bone scans starting at the early
      vascular phase. These findings suggestive of RSDS led to treatment with
      calcitonin, griseofulvin, and pamidronate, all of which were ineffective.
      Laboratory tests showed severe inflammation, promoting investigations for other
      conditions. Spondyloarthropathy was diagnosed based on oligoarthritis with
      sacroiliitis, presence of HLA B27, and a favorable response to non-steroidal
      antiinflammatory therapy. In older patients, edema of the foot with severe
      demineralization and the laboratory evidence of inflammation should suggest a
      spondyloarthropathy.

PMID- 12814767
TI  - A family with a variant form of primary hypertrophic osteoarthropathy restricted
      to the lower extremities.
AB  - We report a case of a family with a variant form of primary hypertrophic
      osteoarthropathy (HOA) restricted to the lower extremities without digital
      clubbing or cutaneous changes. Three family members suffered from pain, swelling
      and hyperhidrosis of both feet. X-rays showed destruction and osteoproliferative
      changes of the metatarsal bones with periostal hyperostosis close to the talus.
      There was an increased 99m-Tc-MDP uptake in the early phase of bone scintigraphy.
      Fibrosis of the marrow with stimulated osteoclastic resorption and the presence
      of detritus synovialitis were visible in a bone and joint biopsy. All known
      infectious, neurologic, metabolic and malignant diseases, which affect the bone
      and joints, were excluded.

PMID- 12814768
TI  - Rheumatoid nodules in systemic lupus erythematosus: a case report.

PMID- 12814770
TI  - Burden of Helicobacter pylori and H. pylori-related diseases in developed
      countries: recent developments and future implications.
AB  - Helicobacter pylori colonizes the gastric mucosa. H. pylori infection is the main
      cause of peptic ulcer and gastric malignancy. This review gives an overview on
      the epidemiology of H. pylori infection and H. pylori-associated diseases in the
      developed world, mainly Europe, and it discusses very recent developments with
      regard to the prevalence and its future implications for H. pylori-associated
      diseases.

PMID- 12814771
TI  - Helicobacter in the developing world.
AB  - Helicobacter pylori in the developing world is associated with many unique
      challenges not encountered in an industrialized setting. The 20% prevalence of
      infection with H. pylori among adolescents in the United States pales in
      comparison to infection rates exceeding 90% by 5 years of age in parts of the
      developing world. While H. pylori within the developed world is associated with
      gastritis, which may lead to peptic ulcer and gastric carcinoma, the infection in
      the developing world appears to also be linked with chronic diarrhea,
      malnutrition and growth faltering as well as predisposition to other enteric
      infections, including typhoid fever and cholera. Once identified, treatment of H.
      pylori within the developing world presents increased difficulties due to the
      frequency of antibiotic resistance as well as the frequency of recurrence after
      successful treatment. Control, and possibly eradication, of H. pylori could
      likely be achieved through increased standards of living and improved public
      health, as it has in the industrialized world. However, these measures are
      distant objectives for most developing countries, making long-term control of the
      organism dependent on the development and administration of an effective vaccine.

PMID- 12814772
TI  - Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA)
      and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter
      pylori.
AB  - Helicobacter pylori has elaborated a unique set of virulence factors that allow
      it to colonise the stomach wall. These factors include urease, helicoidal shape,
      flagella and adhesion molecules. Here we discuss the molecular characteristics
      and mechanisms of action of the vacuolating cytotoxin, VacA, and the neutrophil
      activating protein, HP-NAP. Their activities are discussed in terms of tissue
      alterations, which promote the release of nutrients necessary for the growth and
      survival of the bacterium in its nutrient-poor ecological niche.

PMID- 12814773
TI  - Helicobacter pylori antigen-specific T-cell responses at gastric level in chronic
      gastritis, peptic ulcer, gastric cancer and low-grade mucosa-associated lymphoid
      tissue (MALT) lymphoma.
AB  - Host T-cell response to Helicobacter pylori is important for the clinical outcome
      of the infection. A Th1-polarized response, preferentially against CagA, is
      associated with peptic ulcer, whereas mixed Th1 and Th0 responses are present in
      non-ulcer gastritis. A deregulated H. pylori-driven Th0 cell-dependent B-cell
      activation is found in low-grade B-cell lymphoma of mucosa-associated lymphoid
      tissue.

PMID- 12814774
TI  - Priming and expression of immune responses in the gastric mucosa.
AB  - This review deals with the induction and expression of immune responses in the
      human stomach following mucosal immunisation. As prerequisites for developing a
      Helicobacter pylori vaccine, the role of gastric inflammation, in particular
      inflammation induced by H. pylori infection, as well as lymphocyte homing within
      the common mucosal immune system, and the importance of immunisation route are
      discussed.

PMID- 12814775
TI  - Animal models of Helicobacter pylori infection and disease.
AB  - The acceptance of Helicobacter pylori as a major human pathogen has necessitated
      the development of animal models to help elucidate the pathogenic mechanisms of
      this bacterium and aid in the development of improved strategies for the
      treatment of gastric disease. Appropriate models, utilising a range of animal
      species, have been developed to examine factors such as the influence of host
      responses and bacterial factors in disease development and the success of new
      therapeutic regimens, including vaccination, to cure infection.

PMID- 12814777
TI  - Allometric cascade: a model for resolving body mass effects on metabolism.
AB  - Expanding upon a preliminary communication (Nature 417 (2002) 166), we here
      further develop a "multiple-causes model" of allometry, where the exponent b is
      the sum of the influences of multiple contributors to control. The relative
      strength of each contributor, with its own characteristic value of b(i), is
      determined by c(i), the control contribution or control coefficient. A more
      realistic equation for the scaling of metabolism with body size thus can be
      written as BMR=MR(0)Sigmac(i)(M/M(0))(bi), where MR(0) is the "characteristic
      metabolic rate" of an animal with a "characteristic body mass", M(0). With M(0)
      of 1 unit mass (usually kg), MR(0) takes the place of the value a, found in the
      standard scaling equation, b(i) is the scaling exponent of the process i, and
      c(i) is its control contribution to overall flux, or the control coefficient of
      the process i. One can think of this as an allometric cascade, with the b
      exponent for overall energy metabolism being determined by the b(i) and c(i)
      values for key steps in the complex pathways of energy demand and energy supply.
      Key intrinsic factors (such as neural and endocrine processes) or ecological
      extrinsic factors are considered to act through this system in affecting
      allometric scaling of energy turnover. Applying this model to maximum vs. BMR
      data for the first time explains the differing scaling behaviour of these two
      biological states in mammals, both in the absence and presence of intrinsic
      regulators such as thyroid hormones (for BMR) and catecholamines (for maximum
      metabolic rate).

PMID- 12814776
TI  - The quest for a vaccine against Helicobacter pylori: how to move from mouse to
      man?
AB  - Several lines of evidence from experimental animal models of infection have
      clearly demonstrated the feasibility of a prophylactic and therapeutic vaccine
      against Helicobacter pylori. However, comparatively few clinical studies have
      been carried out to evaluate whether the positive results obtained in animals can
      be reproduced in humans. The preliminary results obtained with single component,
      mucosally delivered vaccines have shown very limited results thus far. Very good
      immunogenicity and safety profiles are now being obtained with parenterally
      delivered, aluminium hydroxide-adjuvanted multicomponent candidate vaccines. For
      sure, better vaccine formulations, better antigen preparation(s), better
      adjuvants, and better delivery systems have to be designed and tested for safety
      and immunogenicity. These studies are also needed for deciphering those aspects
      of the effector immune responses that correlate with protection against H. pylori
      infection and disease.

PMID- 12814778
TI  - Effects of progesterone and estradiol on the reproductive axis in immature
      diploid and triploid rainbow trout.
AB  - In fish species, many studies demonstrated the crucial role of estradiol (E2) in
      the development of the reproductive axis, but progesterone (P) has been described
      mainly as a precursor steroid and no clear role by itself has been reported.
      Moreover, a cooperative effect of P (or another progestin) and E2 in fish has
      never been reported to our knowledge. In the present work, we investigated the
      effects of P, alone or in combination with E2, on the reproductive-axis of
      immature rainbow trout (Oncorhynchus mykiss). Liver vitellogenin and estradiol
      receptor (rtER) mRNA levels increased after E2 treatment, but were unchanged by P
      treatments as a reflection of peripheral action of steroids. In contrast, at the
      pituitary level, LH contents increased after E2 and/or P treatments. Focusing on
      the brain level, we confirmed a clear up regulation of rtER expression by E2 in
      sterile triploid females, and we also demonstrated a similar stimulating effect
      of P alone but no cooperative effect together with E2. In conclusion, our data
      demonstrate that in immature trout, prior to the beginning of the first
      reproductive cycle, unlike E2, P is able to stimulate the reproductive brain
      pituitary axis without affecting vitellogenin synthesis in the liver.

PMID- 12814779
TI  - Hormonal and metabolic responses to overfeeding in three genotypes of ducks.
AB  - Muscovy, Pekin and Mule duck are different in their body weight. To make a valid
      comparison in the lipid metabolism between these three genotypes, overfeeding was
      carried out by providing the animals with amounts of food in proportion to their
      body weight. Under these conditions, Muscovy ducks developed a strong liver
      steatosis, whereas it was not very pronounced in the Mule ducks and even less in
      the Pekin ducks. On the contrary, Pekin ducks showed a much marked extrahepatic
      fattening. At the beginning of overfeeding, there was a similarity in the three
      genotypes as regards the post-heparin lipoprotein-lipase (LPL) activity and the
      insulin and glucagon concentrations. After 10 days of overfeeding, the LPL
      activity dramatically fell in Muscovy and in Mule ducks, whereas it remained
      steady in Pekin ducks. Compared to values found at the beginning of the
      overfeeding period, plasma glucagon and insulin shown no evolution, except for
      the insulin of Pekin ducks which was dramatically higher. Those data suggest that
      high plasma insulin concentrations measured in Pekin ducks after 10 days of
      overfeeding can be responsible for the maintenance of the LPL activity, which
      favors the extrahepatic fattening to the detriment of liver steatosis.

PMID- 12814780
TI  - Daily variations in the influence of noradrenaline on preferred ambient
      temperature of the Siberian hamster.
AB  - Daily variations in sensitivity to noradrenaline (NA) and the activation of
      nonshivering thermogenesis (NST) are important for survival under a potentially
      wide range of environmental conditions. However, little is known regarding the
      ability of the Siberian hamster and other species to activate NST in the day and
      night when they may be subjected to marked variations in environmental
      temperature. In this study, the effects of acclimation temperature and time of
      day on the behavioral thermoregulatory response to NA injections in Siberian
      hamsters (Phodopus sungorus) was investigated. Hamsters were acclimated for 4
      weeks to 23 degrees C and a L:D 12:12 h photoperiod. After acclimation, preferred
      ambient temperatures (PT(a)) in saline- and NA-injected animals were measured
      continuously in the temperature gradient system. NA (0.6 mg/kg; s.c.) was given
      every 4 h while PT(a) was monitored. After NA injections there was a rapid drop
      in PT(a), decreasing to approximately 15 degrees C within 10-20 min after each NA
      injection. Following 4 weeks of acclimation to 10 degrees C and a L:D 8:16 h
      photoperiod, the same hamsters were re-tested in the temperature gradient system.
      Cold acclimation led to an accentuation in the behavioral response with a
      decrease in PT(a) of approximately 10 degrees C. The maximal decrease in
      preferred ambient temperatures was recorded during the light phase of the day and
      during the second part of the night. Lowering of PT(a) after NA allows for rapid
      dissipation of the heat from NST. Overall, the behavioral response reflects the
      daily changes in brown adipose tissue sensitivity to NA and thus capacity for
      NST.

PMID- 12814781
TI  - Production of insulin-like growth factor binding-proteins by bovine
      adrenomedullary cells: differential regulation by IGF-I and dexamethasone.
AB  - In the present study we examined the production of insulin-like growth factor
      binding proteins (IGFBPs), in chromaffin cells, a model system for sympathetic
      neurons. Four IGFBPs of approximately 27, approximately 31, approximately 36 and
      a doublet of approximately 45-50 kDa, detected in Western ligand blots of
      conditioned medium, were identified in Western immunoblots as IGFBP-4, IGFBP-5,
      IGFBP-2 and IGFBP-3, respectively. In ligand blots IGFBP-3 and IGFBP-4 appeared
      as the most prominent species. IGF-I (1 nM) enhanced release of IGFBP-3 while
      dexamethasone (1 nM) diminished release of IGFBP-4. No significant proteolytic
      degradation of the IGFBPs was demonstrated. Cycloheximide completely attenuated
      release of the IGFBPs, indicating dependency on new synthesis of the proteins.
      These findings are consistent with autocrine modulation of the IGF system in
      bovine adrenomedullary chromaffin cells by IGFBPs. Furthermore, the specific
      stimulatory and inhibitory effects of IGF-I and dexamethasone, respectively, on
      release of the predominant species of IGFBP-3 and IGFBP-4, suggested that IGFBP
      production may be selectively modulated in a positive and negative manner.

PMID- 12814782
TI  - Digestive efficiency of a generalist avian feeder, the Cape White-eye (Zosterops
      pallidus).
AB  - Digestive processes determine whether the particular diet of a bird is utilized
      efficiently and whether energetic demands are met. Assimilation efficiency is
      often used as an index of whether a diet is digested optimally. Studies on the
      digestive processing of generalist feeders are scarce. Cape White-eyes (Zosterops
      pallidus) have a diverse diet of fruit, nectar and insects. The nutrient contents
      of these three diets vary considerably and require quite different digestive
      processing. This study compared the digestive efficiencies of Cape White-eyes on
      these three diets by measuring transit times and assimilation efficiency. Cape
      White-eyes lost body mass significantly when fed fruit, while they maintained and
      gained body mass on nectar and mealworm diets, respectively. Assimilation
      efficiency varied significantly between the three diet types
      (nectar>mealworms>apples). When given a choice of diets, Cape White-eyes selected
      the diet, which was most efficiently digested and yielded the greatest energetic
      reward. Diet preference trials further showed that Cape White-eyes regulated
      daily energy intake. Assimilation efficiency depends on the accessibility of
      nutritional contents of a diet. Cape White-eyes did not maximize assimilation
      efficiency. Instead, they adjusted transit time to maximize the rate of energy
      gain per gram of food in order to maintain energy balance.

PMID- 12814783
TI  - Does the ostrich (Struthio camelus) coprodeum have the electrophysiological
      properties and microstructure of other birds?
AB  - The ostrich is unique among birds in having complete separation of urine and
      faeces. The coprodeal epithelium is thus during dehydration exposed to a fluid
      500 mOsm hyperosmotic to plasma. We have investigated whether the coprodeum is
      adapted like a mammalian bladder. The coprodeal epithelium was studied by
      electrophysiology in the Ussing chamber, and the anatomy by light microscopy and
      scanning electron microscopy. ELECTROPHYSIOLOGY: The short-circuit current (SCC)
      and open circuit electrical potential difference were recorded. The change
      induced by 0.1 mmol mucosal amiloride was recorded. An average basal SCC of 162+/
      29 microA/cm(2) was observed, and a resistance of 297+/-34 Omega cm(2)
      calculated. These values are as observed in other avian coprodea. The resistance
      is much lower than in mammalian bladders (10000 Omega cm(2)). The amiloride
      sensitive SCC, equal to net sodium absorption, was approximately 5
      micromol/cm(2)h as observed in other avian species. ANATOMY: The mucosal membrane
      is composed of broad irregular folds with very short intestinal glands containing
      an unusually high proportion of goblet cells. CONCLUSION: The ostrich coprodeum
      is not adapted like a mammalian bladder. The abundance of goblet cells results in
      a copious secretion of mucus that establishes a thick unstirred layer giving
      effective osmotic protection.

PMID- 12814784
TI  - Autoradiographic distribution of neuropeptide Y binding sites in the brain of the
      carp Cyprinus carpio L. (Cyprinidae, Teleostei).
AB  - The present study reports the distribution of neuropeptide Y (NPY)-binding sites
      in the brain of the adult carp Cyprinus carpio L. Radioiodinated NPY was used as
      tracer in the autoradiographic procedure. The NPY-binding sites (NPY-bs) were
      widely distributed in the carp brain. Generally, a good match was observed
      between the distribution of NPY-bs and the distribution of NPY-immunoreactive
      (NPY-ir) elements previously reported in the forebrain of the carp. Low to
      moderate concentration of NPY-bs were found in the telencephalon, this finding
      indicates that NPY may play a role in the processing of olfactory inputs and in
      more complex behaviours like spatial learning acquisition and retention, whose
      importance could correlated with similar results obtained in mammals. Moreover,
      in the rhombencephalon, the presence of NPY-bs at level of lobus vagus and the
      lobus facialis suggests that NPY may be implicated in food-seeking behaviour and
      swallowing reflex.

PMID- 12814785
TI  - Branchial and renal handling of urea in the gulf toadfish, Opsanus beta: the
      effect of exogenous urea loading.
AB  - The objective of this study was to determine whether the pulsatile facilitated
      diffusion transport mechanism (tUT) found in the gills of the gulf toadfish
      (Opsanus beta) and the active secretion transporter thought to be present in its
      kidney could be saturated when faced with elevated plasma urea concentrations.
      Toadfish were infused with four consecutive exogenous urea loads at a rate of 0,
      150, 300 and 600 micromol kg(-1) h(-1). Initial plasma and urine urea
      concentrations were 8.1+/-0.9 and 12.4+/-1.5 mmol l(-1), respectively, and
      steadily increased with increasing infused loads of urea to a maximum of 36.8+/
      2.8 mmol l(-1) in the plasma and 39.8+/-6.5 mmol l(-1) in the urine. There was
      only a very weak relationship (r=0.17) between pulse size (measured as branchial
      excretion during pulsatile excretion of urea) and plasma urea concentration
      (slope=9.79 micromol-N kg(-1) per mmol-N l(-1); P<0.05) suggesting that the
      branchial excretion mechanism was already saturated at normal plasma urea
      concentrations. Urine flow rate (0.15+/-0.03 ml kg(-1) h(-1)) and glomerular
      filtration rate (0.025+/-0.004 ml kg(-1) h(-1)) remained constant throughout the
      experiment despite the increased volume load. Renal urea secretion rate
      maintained a strong linear relationship (r=0.84) to plasma urea levels
      (slope=0.391 micromol-N kg(-1) h(-1) per mmol-N l(-1); P<0.001) with no
      observable transport maximum, suggesting that the renal secretory transport
      mechanism was not saturated even at plasma urea levels well above normal, in
      contrast to the branchial excretion mechanism.

PMID- 12814786
TI  - Central, but not peripheral, glucagon-like peptide-1 inhibits crop emptying in
      chicks.
AB  - We investigated the effect of central and peripheral glucagon-like peptide-1 (GLP
      1) on crop emptying in growing chicks. Intracerebroventricular injection of two
      concentrations of GLP-1 (15 and 60 pmol) similarly suppressed crop emptying,
      compared with control chicks. The delay in crop emptying induced by GLP-1 (15
      pmol) was partly attenuated by co-administration with exendin (5-39) (600 pmol),
      a GLP-1 receptor antagonist, although exendin (5-39) alone did not affect crop
      emptying. On the other hand, intraperitoneal administration of several doses of
      GLP-1 (120, 300 and 3000 pmol) did not alter crop emptying. The present study
      revealed that central, but not peripheral, GLP-1 inhibits crop emptying in
      chicks.

PMID- 12814787
TI  - Characterization of lipoproteins from the turtle, Trachemys scripta elegans, in
      fasted and fed states.
AB  - The lipid and apolipoprotein composition of VLDL, IDL, LDL, HDL(2) and HDL(3)
      were examined in the turtle, Trachemys scripta elegans, in fasted and fed states.
      The lipid composition of turtle lipoproteins was very similar to their human
      counterparts. The major apolipoprotein found in LDL, IDL and VLDL, which has a
      molecular weight of approximately 550 kD, is a homologue of apoB100. The major
      apolipoprotein found in both HDL(2) and HDL(3), has a molecular weight of 28-kD
      and is homologous to human apoA-I. HDL(3) also contains a 6.5 kD protein that is
      homologous to apoA-II, while HDL(2) has two low molecular weight proteins of 6 kD
      and 7 kD which are also found on the triglyceride rich lipoproteins (TRL). The 7
      kD protein is homologous to apoC-III, while the 6 kD protein has a similar size
      and distribution as apoC-II or apoC-I. In addition, HDL(2) also possesses a
      protein of 15.8 kD that has no obvious mammalian homologue. In both size and
      apolipoprotein composition, turtle HDL(2) resembles human HDL(2b) while turtle
      HDL(3) resembles human HDL(3). In the fasted state, turtles contained very little
      TRL. When fed a high fat diet, the amount of IDL and LDL sized particles
      increased significantly.

PMID- 12814788
TI  - Multiple forms of arylalkylamine N-acetyltransferase (NAT) from cockroach female
      colleterial glands and activity changes during oocyte maturation.
AB  - Arylalkylamine N-acetyltransferase (NAT) from the female colleterial glands of
      Periplaneta americana showed activity peaks at pH 6.0 and 9.5 and the pH profile
      changed during oogenesis. The left gland contained higher activity than the right
      gland but the right gland also contained recognizable activity. The patterns in
      activity change depended on the substrate used, tryptamine (TN) or serotonin (5
      HT). When TN was used as the substrate, the alkaline peak was higher than the
      acidic peak. In contrast, when 5-HT was used, the acidic peak was much higher
      than the alkaline peak. This suggests that at least two NATs are present in this
      species that are specific to pH and substrate species. Of the four combinations
      of the two pH ranges and two substrate indolamines, the enzyme activity that
      showed a similar change to the oocyte maturation was obtained in the combination
      of pH 6.0 and TN. TN was actually detected in the colleterial glands by
      fluorescent measurements according to Hess and Uderfriend [J. Pharmacol. Exp.,
      127 (1959) 175-177]. It peaked on the 6th day of emergence, which corresponded to
      the first rise of oocyte length and yolk accumulation, whereas a small peak
      appeared in the phase of the second rise. TN, or more likely N-acetyl TN, may
      therefore be involved in the regulation of oocyte maturation which could be a
      novel mechanism in oocyte maturation.

PMID- 12814789
TI  - Biophysical characterization of a large conductance anion channel in hypodermal
      membranes of the gastrointestinal nematode, Ascaris suum.
AB  - Patch-clamp recordings from muscle- and cuticle-facing hypodermal membranes of
      the gastrointestinal nematode Ascaris suum reveal a high-conductance, voltage-
      sensitive Ca(2+) -dependent Cl(-) channel. The hypodermal channel has a
      conductance of 195 pS in symmetrical 160 mM NaCl. The open probability of the
      channel is highly voltage-sensitive, and channel activity is not observed when
      Ca(2+) is reduced to <100 microM. The channel is permeable to organic anions that
      are major end-products of carbohydrate metabolism in A. suum, including acetate,
      butyrate and 2-methylvalerate. The conductances and relative permeabilities of
      these organic anions are inversely related to size, with 2-methylvalerate being
      only approximately 3% as permeable as Cl(-). The diameter of the channel pore was
      12.3+/-0.2 A, calculated from the relative permeability coefficients of Cl(-) and
      the organic anions. Results of this study are consistent with the hypothesis that
      the large conductance anion channel in A. suum hypodermal membranes provides a
      low energy pathway for organic anion excretion from the hypodermal compartment,
      followed by diffusion across the aqueous channels of the cuticle matrix.

PMID- 12814790
TI  - Physiology and endocrinology of zinc accumulation during the female squirrelfish
      reproductive cycle.
AB  - Females of the squirrelfish family (Holocentridae) accumulate higher levels of
      hepatic zinc than any other studied animal. This accumulation is accompanied by
      high expression of the zinc-binding protein, metallothionein (MT), and is
      strongly correlated to the onset of sexual maturity. In an attempt to further
      characterize the timeframe of this accumulation, and to possibly discern any
      potential mediators, we examined the physiology and endocrinology of the yearly
      reproductive cycle of mature female squirrelfish. There are two separate
      reproductive events during the year in December-January and again in March-April,
      as evidenced by peaks in ovarian growth, VTG production, steroid levels, zinc
      accumulation and redistribution. Increased hepatic zinc seems to be preceded by a
      necessary increase in MT, but this was not clearly correlated to plasma 17beta
      estradiol, testosterone, or progesterone levels. The plasma zinc protein
      vitellogenin (VTG) is one, but probably not the predominant, vehicle for the
      transport of hepatic zinc to the ovary.

PMID- 12814791
TI  - Heart rate responses to cooling in emu hatchlings.
AB  - Among fluctuations of instantaneous heart rate (IHR) in newly hatched chicks,
      heart rate (HR) oscillation with a mean frequency of 0.7 Hz has been designated
      as Type II HR variability characterized by low frequency (LF) oscillation [Comp.
      Biochem. Physiol. Part A 124 (1999) 461]. In response to exposure to lowered
      ambient temperature (Ta), chick hatchlings raised their HR baseline accompanied
      with the production or augmentation of Type II HR oscillation, indicating that LF
      oscillation is a phenomenon relating to thermoregulation [J. Therm. Biol. 26
      (2001) 281]. In emu hatchlings that are precocial like chickens, Type II HR
      oscillation also occurred, but less frequently in comparison with chick
      hatchlings [Comp. Biochem. Physiol. Part A 131 (2002) 787]. This present
      experiment was conducted to elucidate how IHR of emu hatchlings responds to
      changes in Ta. Six hatchlings were measured for IHR and skin temperature (Ts)
      during a 3-h period when they were exposed to controlled Ta (ca. 35 degrees C),
      lowered Ta (ca. 15-30 degrees C) and again the controlled Ta for individual 1-h
      periods. In response to all the cooling and re-warming procedures, HR baseline
      changed depending upon the intensity of the Ta differences; i.e. large
      differences of Ta produced large changes in HR. HR fluctuations tended to augment
      during cooling with a few exceptions, but LF oscillation was not produced. Thus,
      LF oscillation, which was scarce even at the controlled Ta, could not be used as
      a thermoregulatory indicator in emus.

PMID- 12814792
TI  - Stressor-dependent regulation of the heat shock response in zebrafish, Danio
      rerio.
AB  - Heat shock transcription factors (HSFs) regulate expression of heat shock
      proteins (Hsps). We have previously shown that in zebrafish a unique isoform,
      zHSF1b, disappears concomitant with heat shock-induced Hsp70 expression. To
      characterize the role of zHSF1a and zHSF1b isoforms in the regulation of the
      stress response in vivo, we have carried out cadmium (10-100 microM) and copper
      (10-30 microM) exposures in order to specify whether the disappearance of HSF1b
      is specific for heat stress. After 4-h metal exposures we analyzed the expression
      of hsp70, zHSF1a, zHSF1b and metallothionein (MT) by reverse transcriptase
      polymerase chain reaction in zebrafish liver, gonads and gills. Although cadmium
      is a known inducer of Hsps, it did not affect hsp70 expression significantly in
      the studied tissues. Induction of hsp70 was observed upon copper exposure in
      liver and gonads, but not in gills. Neither metal affected the zHSF1a/b ratio.
      Both cadmium and copper exposure caused upregulation of MT, regulator of metal
      homeostasis and detoxification, confirming that the tissues were subjected to
      metal loads. Thus, hsp70 appears to be more weakly induced upon metal exposure
      than in response to heat shock and HSF1 isoforms may participate in stressor
      specific regulation of hsp70.

PMID- 12814793
TI  - Body fat and condition in sperm whales, Physeter macrocephalus, from southern
      Australian waters.
AB  - Blubber thickness (n=102) and lipid content (n=37) were measured in sperm whales
      from three mass stranding events on the west and north-west coasts of Tasmania,
      Australia in February 1998. Blubber thickness was highly variable, ranging from
      43.0 to 168.0 mm (mean 98.4+/-18.4 mm) while lipid fat content, also highly
      variable, ranged from 16.19 to 89.34% (mean 49.2+/-17.9%). Blubber thickness was
      significantly and positively related to total length, but a blubber thickness
      index based on the residuals of this relationship was not related to age, sex or
      reproductive condition. No relationship was found between blubber thickness index
      and blubber lipid content, indicating that blubber thickness may not provide a
      comprehensive indication of body fat condition in sperm whales when only measured
      at a single site. Blubber lipid content was not related to total length, age or
      sex. Blubber lipid content was stratified vertically throughout the blubber
      layer, suggesting that the inner blubber layer may be a more active site for
      lipid deposition and mobilisation, while the outer blubber layer may serve in a
      structural or thermoregulatory role. The social structure and foraging ecology of
      this species may serve to minimise the need to rely on stored energy reserves to
      meet reproductive energy requirements. In addition, the broader role of blubber
      for structural, buoyancy and insulative functions coupled with high individual
      variability may cause a lack of obvious relationships between these variables and
      body size, age, sex and reproductive state in this species.

PMID- 12814794
TI  - Aging research in India.
AB  - Research on aging in India has been well documented since ancient times. As way
      back as 3000-1500 BC, the Indian medical system of Ayurveda was used as a means
      for the prevention of the effects of aging and generation of disease in organs or
      the whole organism, respectively. In recent years, the focus has been demographic
      studies on different aspects of aging and has been in isolation. Molecular
      aspects of aging have been addressed only by a few groups of scientists which has
      focused on regulation of gene expression, DNA damage and repair, development of
      immunochemical reagents to detect oxidative DNA damage and assessing the levels
      of circulating antibodies to reactive oxygen species modified DNA (ROS-DNA), etc.
      This review aims to recapitulate various research studies on aging since 3000 BC
      to date.

PMID- 12814795
TI  - Molecular mechanisms underlying osteoclast formation and activation.
AB  - Osteoporosis is one of the leading causes of morbidity in the elderly and is
      characterized by a progressive loss of total bone mass and bone density. Bone
      loss in osteoporosis is due to the persistent excess of osteoclastic bone
      resorption over osteoblastic bone formation. Receptor activator of NFkappaB
      ligand (RANKL) critically regulates both osteoclast differentiation and
      activation. TRAFs appear to be central coupling molecules in the signal
      transduction pathways that regulate osteoclastogenesis, cathepsin K is the major
      mediator of osteoclastic bone resorption, and sex steroids and aging also affect
      osteoclastogenesis and osteoclast activity. However, bone homeostasis depends
      upon the intimate coupling of bone formation and bone resorption, wherein both
      osteoclasts and osteoblasts exert vital stimulatory and inhibitory effects upon
      each other via molecules such as RANKL, TGFbeta, PDGF, BMP2, and Mim-1. This
      review will highlight some of the major features of the complex circuit of
      cytokines, growth factors, and hormones that underlies the formation and function
      of osteoclasts and the dynamic equilibrium that marks the interaction between
      osteoclasts and osteoblasts.

PMID- 12814796
TI  - Is life span extension in single gene long-lived Caenorhabditis elegans mutants
      due to hypometabolism?
AB  - The nematode C. elegans is widely used in aging research largely because of the
      identification of numerous gene mutations that significantly increase worm
      longevity. While model organisms such as C. elegans can provide important
      insights into aging it is also important to consider the limitations of these
      systems. For example, ectothermic (poikilothermic) organisms are able to tolerate
      a much larger metabolic depression than humans and considering only chronological
      longevity when assaying for long-lived mutants provides a limited perspective on
      the mechanisms by which longevity is increased. In order to provide true insight
      into the aging process additional physiological processes, such as metabolic
      rate, must also be assayed. Currently it is controversial when long-lived C.
      elegans mutants retain normal metabolic function. Resolving this issue requires
      accurately measuring the metabolic rate of C. elegans under conditions that
      minimize environmental stress. Comparisons of metabolic rate between long-lived
      and wild-type C. elegans under more optimized conditions indicate that the
      extended longevity of at least some long-lived C. elegans mutants may be due to a
      reduction in metabolic rate, rather than an alteration of a metabolically
      independent genetic mechanism specific to aging. Consistent with this assertion
      are studies showing that the disruption of mitochondrial function in C. elegans
      can extend worm's longevity, but typically causes worms to grow and develop more
      slowly than wild-type animals.

PMID- 12814797
TI  - Cellular senescence in human keratinocytes: unchanged proteolytic capacity and
      increased protein load.
AB  - In order to assess the activity of cellular proteasome, we developed a method to
      permeabilize keratinocyte monolayers and measure proteasome activities
      intracellularly, using fluorogenic peptide substrates. The observed K(m) did not
      differ significantly in situ and in soluble extracts, and the K(i) of proteasome
      inhibitor MG132 was slightly higher in situ (34nM instead of 4nM). Inhibition
      studies in permeabilized cells showed that MG132 followed competitive inhibition
      patterns, and clasto-lactacystin beta-lactone non-competitive patterns, as
      expected. The observed velocities in situ (500pmoles/min/mg protein) were
      comparable to the best values of proteasome activity in crude cellular extracts.
      These features altogether allowed to identify the in situ activity as that of
      proteasome. To characterize proteasome complexes present in human keratinocytes,
      we analyzed cellular lysates by ultracentrifugation and gel filtration: most
      proteasome activity was associated with PA700-bound, presumably 26S, particles.
      PA28 activator was detected only when cells were treated by gamma interferon.
      Proteasome activities were determined using the in situ method in keratinocytes
      at different stages of replicative senescence. Only a slight decrease of
      proteasome activity per cell was seen at intermediate passages, followed by a
      slight increase in senescent cells. In the same time, the amount of total
      proteins increased notably with cellular ageing. Thus, proteasome activity
      decreased relatively to total proteins, but not relatively to cell numbers. Flow
      cytometry confirmed that the size of aged keratinocytes increased with the ageing
      marker beta-galactosidase.

PMID- 12814798
TI  - An in vitro model of caloric restriction.
AB  - The mechanisms underlying the ability of caloric restriction (CR) to extend life
      span and enhance stress responsiveness remain elusive. Progress in this area has
      been slow due to the complexities of using animals for CR studies and assessing
      life span as the measure of CR effectiveness. It is therefore of great interest
      to develop in vitro models of CR. Here we use sera obtained from either Fisher
      344 rats or Rhesus monkeys that were fed ad libitum (AL) or CR diets to culture
      various cell types. We show that treatment of cultured cells with CR sera caused
      reduced cell proliferation, enhanced tolerance to oxidants and heat, and
      heightened expression of stress-response genes. These phenotypic features mirror
      the effects of CR in animals. Supplementation of CR serum with insulin and
      insulin-like growth factor (IGF)-1 partially restored the proliferative and
      stress-response phenotype that was seen in cells cultured with AL serum,
      indicating that reduced levels of insulin and IGF-1 likely contribute to the CR
      related effects. This in vitro cell culture model recapitulates key in vivo
      proliferative and stress-response phenotypic features of CR, and further suggests
      that endocrine mechanisms contribute to the enhanced stress responsiveness
      observed in CR animals.

PMID- 12814799
TI  - Candidate chromosomal regions for genes involved in activation of alternative
      lengthening of telomeres in human immortal cell lines.
AB  - Either telomerase or alternative mechanisms known as alternative lengthening of
      telomeres (ALT) are activated in human immortal cells to maintain or lengthen
      their telomeres. To screen candidate chromosomes harboring gene(s) involved in
      activation of the telomere maintenance mechanisms that are repressed in normal,
      mortal cells and lost in immortal cells, we examined loss of heterozygosity (LOH)
      on the 22 autosomes and the X chromosome in 22 in vitro established human
      immortal cell lines consisting of 9 telomerase-positive cell lines and 13 ALT
      positive cell lines. For detecting LOH, PCR analysis was performed with 66
      polymorphic microsatellite markers from candidate genomic regions previously
      implicated for putative human senescence genes, telomerase repressor genes, or
      tumor suppressor genes. LOH involving chromosome 8 was observed at 25 of 62 (40%)
      informative loci in 8 of 13 (61%) ALT-positive cell lines. Particularly, when
      assayed with D8S339 adjacent to the Werner's syndrome gene, LOH was found in 6 of
      12 (50%) informative ALT-positive cell lines. In contrast, no LOH on chromosome 8
      was detected at 41 informative loci in any of 9 telomerase-positive cell lines.
      No other chromosomes showed high frequencies of LOH common in either ALT-positive
      or telomerase-positive cell lines. Although further LOH analysis with additional
      markers remains to define the specific region on chromosome 8, our results
      suggest that gene(s) involved in activation of the ALT pathway in human immortal
      cell lines may localize on chromosome 8.

PMID- 12814800
TI  - Different rates of telomere shortening and telomerase activity reduction in CD8 T
      and CD16 NK lymphocytes with ageing.
AB  - Telomeres are specialised structures located at the end of eukaryotic
      chromosomes, that get short during progressive cell divisions. Therefore,
      telomere may be an indicator of the mitotic history of a cell and it is also a
      determining factor for the residual cell life span. One mechanism, compensating
      for the telomere erosion, involves the induction of telomerase, a
      ribonucleoprotein-enzyme able to synthesize telomeric DNA repeats. In this study,
      old subjects of two consecutive decades were compared with a group of young
      controls to investigate whether ageing-related modifications differently affects
      telomere length and telomerase activity of human peripheral blood CD8 T and CD16
      NK lymphocytes. Telomeres in individual cells were measured by flow-FISH and
      telomerase activity was determined using the TeloTAGGG telomerase PCR ELISA(PLUS)
      kit. Both CD8 T and NK lymphocytes showed an age-associated loss of telomeres at
      rates that were different between the subsets together with an age-associated
      reduction of telomerase activity that was progressive in CD8 and late in NK
      lymphocytes. We can assume that preserved innate immune response in the elderly
      is due to the negligible telomere shortening and the maintained telomerase
      expression that could allow NK cells of octogenarians to delay replicative
      senescence.

PMID- 12814801
TI  - The effect of IL-12 on clinical and laboratory aspects of experimental SLE in
      young and aging mice.
AB  - IL-12 plays a crucial role in a variety of immune responses that are involved in
      immuno-senesence and autoimmune diseases. Experimental SLE can be induced in mice
      by the monoclonal anti-DNA autoantibody bearing the 16/6Id. Aging mice are less
      susceptible to disease induction. We evaluated the in vivo effects of IL-12 on
      several parameters related to aging and to experimental SLE. Young (2 months) and
      aging (10 months) mice that were or were not immunized with the 16/6Id were
      treated with IL-12. IL-12 treated unimmunized BALB/c and C3H.SW mice had
      significant elevated levels of anti-DNA antibodies. A high percentage of these
      mice had glomerular immune complex deposits (ICD). IL-12 treatment resulted in
      significant increase of IL-1 and IFN-gamma and a decrease of IL-10 production in
      unimmunized mice. The same IL-12 induced changes were observed in mice with
      experimental SLE but were less pronounced than in normal mice. In general, all
      the effects in SLE afflicted mice were more prominent in aging than in young
      mice. Treatment of mice with experimental SLE upregulated IL-1, IL-2, IFNgamma
      and downregulated IL-10. These changes were observed in the groups of young as
      well as old mice. In conclusion, administration of IL-12 to aging mice reversed
      their Th1/Th2 cytokine profile and thus rendered them vulnerable to the induction
      of experimental SLE.

PMID- 12814802
TI  - Increased circulating Interleukin-18 levels in centenarians with no signs of
      vascular disease: another paradox of longevity?
AB  - Interleukin (IL)-18 is highly expressed in macrophages from human atherosclerotic
      plaques, suggesting its involvement in ischemic syndromes. We evaluated IL-18 and
      IL-18 binding protein (BP) in healthy centenarians, as longevity is characterized
      by a reduced incidence of ischemic events. For comparison, patients with chronic
      ischemic syndromes (CIS) were evaluated. Serum IL-18 and IL-18BP levels were
      measured by non-cross-reacting ELISA in 16 healthy centenarians and in two age
      control populations, each of 18 healthy individuals aged 55.9+/-1.43 and 74.3+/
      1.35, respectively, as well as in 23 CIS patients, and another cohort of 23
      healthy subjects that were age- and sex-matched with CIS patients. Centenarians
      displayed significantly higher total IL-18 serum levels compared to each control
      group. Elevated IL-18 levels were also present in CIS patients. However,
      centenarians had a significant higher level of IL-18BP compared to the cohort of
      23 controls (P=0.0014), and compared to CIS patients (P=0.043); as a result
      centenarians exhibited a lower level of free IL-18 than CIS patients. The present
      results indicate that quenching of IL-18 by IL-18BP may explain the apparent
      paradox of elevated serum IL-18 with no vascular signs in centenarians.

PMID- 12814803
TI  - Heat-induced expression of a molecular chaperone decreases by selecting for long
      lived individuals.
AB  - The 70 kDa heat-shock protein (Hsp70) exhibits a broad range of chaperone
      functions that respond both to internal and external stresses, and its heat
      induced expression both declines with age and reduces age-specific mortality
      rates. Here we test for changes in both longevity and the level of Hsp70-induced
      expression as correlated responses to selection on both heat-stress resistance
      and longevity in D. melanogaster. Three replicated H lines were heat-stress
      selected and compared to their respective non-selected controls (C lines) in the
      25th generation of heat-stress selection. The direct response in heat-stress
      resistance was 56% in males and 38% in females. Heat-stress selection improved
      longevity in males at normal temperatures. All lines were subsequently subjected
      to one generation of truncation selection on longevity (selection intensity,
      i=1.28 for H lines and 1.36 for C lines). The heat-induced Hsp70 expression seems
      to increase very weakly by heat-stress selection but shows a dramatic and
      persistent decline by selecting for long-lived flies. A mechanism of longevity
      selection, involving changes in Hsp70 regulation, is suggested.

PMID- 12814804
TI  - Characterization of the heat shock response in mature zebrafish (Danio rerio).
AB  - Heat shock proteins (Hsps) are involved in many physiological and pathological
      processes and are diminished with age in a variety of species. As zebrafish
      embryos have proven to be excellent models for studying Hsp response during
      development, we sought to characterize the response in mature zebrafish to
      demonstrate the utility of the zebrafish model in studying late-life diseases and
      the biology of aging. Accordingly, mature zebrafish were exposed to a 37 degrees
      C heat stress and mRNA was isolated from various tissues and subjected to
      analysis by RT-PCR. We found that Hsp70 was upregulated in brain, liver, and
      muscle, while Hsp47 was upregulated in brain, but not liver or muscle.
      Hsp90alpha, Hsp90beta, and heat shock factor 1a (Hsf1a) were expressed in all
      three tissues, but were not upregulated in response to heat stress. A comparison
      of Hsp expression in young versus mature zebrafish revealed decreased basal
      levels of Hsp70 and increased levels of Hsf1a in mature fish. These results
      indicate that the heat shock response is detectable in mature zebrafish and that
      there are age differences in their heat shock response, suggesting that mature
      zebrafish may be a useful model for studying Hsp response during the aging
      process.

PMID- 12814805
TI  - Age-dependent differences in the stimulation of lipid peroxidation in the heart
      of rats during immobilization stress.
AB  - In order to investigate the possible reasons for age-related decrease in
      myocardium resistance to stress, we carried out a study of lipid peroxidation
      (LPO) stimulation features in the myocardium of adult (10-12 months) and aged (22
      25 months) male Wistar rats during immobilization stress. In our studies of
      ascorbate-dependent LPO and induced chemiluminescence, we found that
      immobilization stress is accompanied by decreased efficiency in the induction of
      free radical processes in the heart of aged rats. An important cause of this
      phenomenon may be age-dependent changes in the catalytical properties of the
      cytosolic superoxide dismutase. The pathophysiological consequences of stress
      related, age-dependent decreased efficiency of induction of free radical
      processes in the heart are discussed.

PMID- 12814806
TI  - Supplementation with vitamin E fails to attenuate oxidative damage in aged mice.
AB  - The validity of the oxidative stress hypothesis of aging has sometimes been
      questioned because the administration of low molecular weight antioxidants such
      as alpha-tocopherol does not retard the aging process and extend maximum life
      span. Thus, the goal of the current study was to determine if increased oral
      intake of alpha-tocopheryl acetate indeed results in its augmentation in tissues
      or in their mitochondria, and whether or not this causes an attenuation of
      oxidative damage. Groups of relatively old (21 months) experimental mice were fed
      a diet supplemented with 1.65 g/kg alpha-tocopheryl acetate or the base diet (NIH
      31), for 13 weeks. Supplementation with alpha-tocopheryl acetate increased alpha
      tocopherol concentrations approximately 3-5-fold in plasma and in tissue
      homogenates and approximately 2-3-fold in mitochondria from liver, skeletal
      muscle and heart of the mice. However, supplementation affected neither the rate
      of heart mitochondrial H(2)O(2) generation nor products of lipid peroxidation
      (thiobarbituric acid-reactive substances) and protein oxidation (protein
      carbonyls). Thus, in contrast to life-extending interventions such as caloric
      restriction, that can produce relatively rapid decreases in oxidative damage,
      supplementation with alpha-tocopheryl acetate had little or no impact on the
      steady-state level of cellular oxidative damage. This difference could explain
      why alpha-tocopherol administration has been found to be ineffective in the
      extension of the life span.

PMID- 12814807
TI  - Age-related oxidative inactivation of Na+, K+-ATPase in rat brain crude
      synaptosomes.
AB  - The study was undertaken to examine the status of Na(+), K(+)-ATPase in aged rat
      brain and to verify if any alteration of this enzyme in aged brain could be
      related to an oxidative damage. The crude synaptosomes from rat brain were
      exposed in vitro to an oxidative stress in the form of a combination of Fe(2+)
      (100 microM) and ascorbate (2 mM) for up to 2 h when increased lipid peroxidation
      (nearly four-fold), extensive protein carbonyl formation and a marked decrease of
      Na(+), K(+)-ATPase activity (approximately 88%) were observed. All these changes
      were prevented by the presence of a chain-breaking anti-oxidant, butylated
      hydroxytoluene (0.2 mM), in the incubation mixture. When the same crude
      synaptosomal membranes from the young (4-6 months) and aged (18-22 months) rat
      brains were analysed, a significant reduction of Na(+), K(+)-ATPase activity
      (nearly 48%) along with significantly elevated levels of lipid peroxidation
      products and protein carbonyls could be detected in the aged animals in
      comparison to young ones. The latter data in combination with the results of in
      vitro experiments imply that the age-related decline of rat brain Na(+), K(+)
      ATPase activity is presumably the consequence of an enhanced oxidative damage in
      aging brain

PMID- 12814808
TI  - The role of free radicals in canine counterpart of senile dementia of the
      Alzheimer type.
AB  - The pathogenesis of Alzheimer's disease is still unknown. In recent time
      oxidative stress has been discussed as an important contributor. In the present
      study we investigated the role of free radicals in the spontaneous canine model
      of Alzheimer's disease. We analysed end-products of lipid peroxidation:
      lipofuscin-like pigments (LFP), protein carbonyls, and vitamin E to obtain data
      on oxidative damage in brain of demented dogs. When the generation of free
      radicals is intensive the toxic products of lipid peroxidation can diffuse from
      the site of the primary formation and merge with erythrocytes. Therefore we also
      determined the level of lipid peroxidation in red blood cells. In brain of
      demented animals the level of LFP increased (to 247%, P<0.05) as well as of
      protein carbonyls (to 438%, P<0.01) while the vitamin E concentration was lowered
      (to 34%, P<0.01) when compared to age-matched non-demented controls. The end
      products of lipid peroxidation have been found increased also in erythrocytes of
      demented dogs (250%, P<0.05). These results indicate intensive production of free
      radicals in brain of animals with dementia which induces damage to erythrocytes.
      Detection of the specific products of free radical damage in blood samples could
      be used for diagnostic purposes.

PMID- 12814810
TI  - A randomized study over 13 cycles to assess the influence of oral contraceptives
      containing ethinylestradiol combined with drospirenone or desogestrel on
      carbohydrate metabolism.
AB  - In this open-label, randomized study we compared the influence of a new oral
      contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone
      (Yasmin) with a reference preparation containing 30 microg ethinylestradiol and
      150 microg desogestrel (Marvelon) on variables of carbohydrate metabolism by
      means of oral glucose tolerance tests at baseline and in the 6th and 13th
      treatment cycle. The mean levels of fasting glucose and insulin were similar at
      baseline and after 13 treatment cycles, whereas C-peptide and free fatty acid
      levels decreased slightly in both groups. All blood glucose and insulin values
      measured in the oral glucose tolerance tests were within normal ranges, despite a
      slight increase in the mean areas under the curves of 0-3 h [AUCs (0-3 h)] of
      both variables from baseline to treatment cycle 13. Differences between both
      treatments were not statistically significant. The mean AUCs (0-3 h) for C
      peptide were not markedly changed in any treatment group. Free fatty acid levels
      decreased by 42% in the drospirenone group and increased by 48.9% in the
      desogestrel group, in terms of means of individual changes. Both preparations
      were well tolerated and equally efficacious regarding contraception and cycle
      control. The mean body weight was slightly decreased in most cycles during
      treatment with the drospirenone combination, as compared to baseline, while it
      was slightly increased versus baseline in all cycles during treatment with the
      desogestrel combination. The combination with drospirenone had less impact on
      blood pressure than the combination with desogestrel. In conclusion, Yasmin, a
      combined low-dose oral contraceptive with 30 microg ethinylestradiol and 3 mg of
      the novel progestogen drospirenone, as well as the reference Marvelon, containing
      30 microg ethinylestradiol and 150 microg desogestrel had little impact on
      carbohydrate metabolism when used for 1 year. The observed changes were small and
      not suggestive of a clinically relevant deterioration of carbohydrate metabolism.

PMID- 12814811
TI  - Efficacy, safety and cycle control of five oral contraceptive regimens containing
      norgestimate and ethinyl estradiol.
AB  - This randomized, multicenter, parallel group study evaluated four new oral
      contraceptive regimens of norgestimate (NGM) and ethinyl estradiol (EE) relative
      to ORTHO TRI-CYCLEN (NGM 180/215/250 microg/EE 35 microg). Healthy women
      (50/group) received three cycles of either ORTHO TRI-CYCLEN Lo (NGM 180/215/250
      microg/EE 25 microg), one of three cyclophasic regimens (NGM cycling 180-250
      microg/EE 35 microg or 25 microg) or ORTHO TRI-CYCLEN. Among all five regimens,
      ovulation suppression, cycle control and safety were generally comparable.
      Presumed ovulation (serum progesterone levels >or=3 ng/mL during Days 19-21 of
      Cycle 3), occurred in 0/41 (0%) subjects on ORTHO TRI-CYCLEN Lo and 3/43 (7%)
      subjects on ORTHO TRI-CYCLEN. Breakthrough bleeding and/or spotting (BBS; % total
      cycles) was 17.2% for ORTHO TRI-CYCLEN Lo and 14.4% for ORTHO TRI-CYCLEN. The
      mean number of days of BBS/cycle for ORTHO TRI-CYCLEN Lo and ORTHO TRI-CYCLEN was
      3.7 and 3.1, respectively, for those subjects with such bleeding. Thus, ORTHO TRI
      CYCLEN Lo appears similar to ORTHO TRI-CYCLEN in inhibiting ovulation and
      providing cycle control.

PMID- 12814812
TI  - Influence of smoking and oral contraceptives on bone mineral density and bone
      remodeling in young women: a 2-year study.
AB  - The objective of the study was to explore the influence of menstrual
      irregularities, oral contraceptives and smoking on bone mineral density (BMD)
      development and bone turnover with time. Healthy young women (n = 118) were
      divided into four categories: (a) women neither smoking nor using oral
      contraceptives; (b) women who were smokers; (c) women using oral contraceptives;
      (d) women who were smoking and using oral contraceptives. They responded to a
      validated questionnaire with 34 questions concerning lifestyle and the Sense of
      Coherence scale (SOC). BMD was measured by dual energy x-ray absorptiometry
      (DEXA). Deoxypyridinoline (DPD) was measured in urine. Data were analyzed by
      multiple linear regression analysis. Among smokers, BMD level decreased during a
      2-year period and smoking was associated with a larger negative change in BMD.
      Use of oral contraceptives moderated the negative impact of smoking. Women using
      oral contraceptives at baseline and with regular bleeding induced by
      contraceptive pills had a significantly higher BMD at baseline and at follow-up.
      They also had lower SOC than women who had natural regular bleedings. Use of oral
      contraceptives in combination with smoking was linked to high alcohol consumption
      and higher frequency of self-reported body weight reduction, which reduced the
      negative BMD change in this category. DPD level and difference were strongly
      associated with estrogen influence. It is concluded that smokers without OCs had
      a negative BMD development and BMD in young women with irregular menstruations
      seems to be improved by OC.

PMID- 12814813
TI  - Emergency contraception pills (ECPs): current trends in United States college
      health centers.
AB  - Access to emergency contraception pills (ECPs) could drastically reduce the high
      rates of unintended pregnancies in college women. In spring 2001, a survey was
      distributed to 139 US college health centers to assess availability of ECPs.
      Those that prescribed ECPs provided additional information about health center
      distribution policies and procedures, provider practice patterns, advertising and
      staff attitudes. Those that did not offer ECPs were asked to state reasons for
      not providing this service and whether FDA approval of dedicated emergency
      contraception products might promote availability. The majority of campuses
      (66.9%) prescribe ECPs; however, many barriers exist to access. Campuses not
      prescribing ECPs cited moral conviction (56.5%) as a main reason for not
      providing this service. Staff and administration attitudes appear to play a major
      role in whether campuses make ECPs available to their students. Despite recent
      advances leading to increased availability of ECPs among college health centers,
      a number of campuses still do not prescribe ECPs.

PMID- 12814814
TI  - Oral and vaginal misoprostol 800 microg every 8 h for early abortion.
AB  - The objective of the study was to evaluate the efficacy and safety of 800 microg
      misoprostol (Cytotec) every 8 h for 24 h for pharmacological abortion; the
      treatment was repeated if abortion did not occur in the first 24-h interval. The
      first misoprostol doses were always self-administered into the vagina; the second
      and third doses could be administered orally or vaginally depending on the amount
      of bleeding. Four-hundred and fifty-two women with gestations between 36 and 63
      days were recruited into the study. The main outcomes assessed were: successful
      abortion (complete abortion without surgery), side effects, mean drop in
      hemoglobin, vaginal bleeding and mean time of return of menstruation. Complete
      abortion occurred in 409/452 (90.5%; 95% confidence interval [CI] 87%, 93%)
      patients. Medication to relieve symptoms was administered to all women before the
      first misoprostol dose. Vaginal bleeding lasted 15.9 +/- 4.4 days. The mean drop
      in hemoglobin, measured 14 days after abortion, was statistically significant (p
      = 0.0001) but without clinical relevance. According to the results obtained, 800
      microg of misoprostol administered every 8 h for 24 h could be a valid method for
      abortion for up to 9 weeks of gestation.

PMID- 12814815
TI  - Mifepristone and misoprostol for early medical abortion: 18 months experience in
      the United States.
AB  - In the first 18 months since mifepristone was approved by the Food and Drug
      Administration (FDA) for use with misoprostol for early medical abortion,
      approximately 80,000 women have been treated. One-hundred thirty-nine adverse
      events were reported to Danco Laboratories LLC and subsequently reported to the
      FDA. Thirteen patients required blood transfusions, 10 patients were treated with
      antibiotics for infection and 6 had a generalized allergic reaction. Fifty
      patients had an ongoing pregnancy, with 48 having suction curettage, leaving 2
      ongoing pregnancies. Thirty-nine patients had a suction curettage for heavy or
      prolonged vaginal bleeding. The overall national experience has been highly
      favorable.

PMID- 12814816
TI  - Effect of progestin-only pill on pituitary-ovarian axis activity during
      lactation.
AB  - We have monitored effects of progestin-only pill (POP) on ovarian activity during
      breastfeeding. Twenty-one women, using barrier methods (BM) of contraception and
      9 women on POP were enrolled 6 weeks postpartum (PP) and followed-up to 18 weeks
      PP. There was little change in plasma follicle-stimulating hormone and
      luteinizing hormone, and no differences between BM and POP. POP did not affect
      plasma estradiol. There was no difference between BM and POP in plasma inhibin B
      concentrations. The size of follicles was similar in both groups in all time
      points. There was an increase in the endometrial thickness from 6 weeks PP to 18
      weeks PP in BM (3.7 +/- 0.5 vs. 5.4 +/- 0.6 mm, p < 0.05), but no differences
      within the POP group or between the treatment groups. POP does not suppress
      gonadotropins nor affect growth of ovarian follicles during breastfeeding. Thus,
      the contraceptive effect of POP is likely mediated through local actions at the
      endometrium and cervix in a manner similar to that in menstruating women.

PMID- 12814817
TI  - The progestative effect of the levonorgestrel-releasing intrauterine system--when
      does it manifest?
AB  - The objective of the study was to evaluate, clinically and sonographically, the
      time required for the progestative effect of the levonorgestrel-releasing
      intrauterine system (IUS, Mirena) to be manifested. Doppler flow of the cervical
      branch and spiral artery of the uterine artery, as well as the endometrial width
      (up to day 10 of the cycle), were evaluated in 36 women carrying levonorgestrel
      releasing IUS 1-2 months after insertion of the device compared to 4-6 months
      after insertion. The rate of intermenstrual bleeding was reduced from 44% during
      the first 2 months, to only 8% of women after 4-6 months of use. Complete
      cessation of menstrual bleeding occurred in 5% after 2 months and in 66% after 4
      6 months following insertion. While there was no change in the Doppler flow in
      the cervical branch of the uterine artery between both groups, there was a
      significant reduction in the subendometrial flow in the spiral artery. This
      observation was reinforced by the demonstration of significant reduction in
      endometrial thickness in the following 4 months of use. The present study has
      demonstrated that the local progestative effect of the levonorgestrel-releasing
      IUS on the endometrium is already manifested within a period of 3 months and over
      after insertion.

PMID- 12814818
TI  - Cu(II) complexation potentiates arginine vasopressin action on nonpregnant human
      myometrium in vitro.
AB  - Copper may influence in vivo and in vitro uterine activity. Recent evidence has
      shown that cupric ions can easily form complexes with oligopeptides like arginine
      vasopressin (AVP). The high complex stability in vitro suggests a possibility of
      complex formation in vivo, in the uterus of intrauterine device users. In vitro
      isometric contractions were recorded in uterine tissues from nonpregnant
      premenopausal women undergoing hysterectomy and the effect of Cu-AVP complex on
      isolated human nonpregnant myometrium was investigated. The addition of the
      Cu(II)-AVP complex to the bath medium led to a concentration-dependent increase
      of the contractile activity. The activity was somewhat lower for the complex (
      log EC(50) of 8.5 +/- 0.2, n = 7) than for AVP, but the difference was not
      statistically significant (p = 0.11). The maximal responses (E(max)) of the
      myometrium strips treated with AVP and the Cu (II)-AVP complex did not differ
      significantly. To assess the effect of presence of Cu (II) in the medium on
      tissue response to AVP, myometrium strips were preincubated for 20 min in the
      medium containing 10(-6) mol/L Cu(II) prior to the administration of AVP. The
      chosen Cu (II) concentration was below the threshold of effect on the spontaneous
      contractile activity in our experiments. The presence of cupric ions in the bath
      caused a significant leftward shift in the concentration-response curve to AVP.

PMID- 12814819
TI  - Further investigation on meloxicam contraceptivity in female rabbits: luteinizing
      unruptured follicles, a microscopic evidence.
AB  - Meloxicam, a selective cyclooxygenase-2 inhibitor, was administered orally or
      intravaginally, to sperm-positive female rabbits to assess its effect on
      ovulation. A single oral dose (20 mg/kg), administered 5 h postcoitus resulted in
      100% contraceptive rate. On the other hand, for females receiving meloxicam
      suppositories (14.9 mg/kg), 5 h postcoitus, the contraceptive rate was 62.5%
      compared to placebo. The decrease in the contraceptive effect of meloxicam
      suppository may be due to the rejection of the dose by some females. Corpora
      lutea, maternal plasma progesterone, ovary fresh weight and maternal body weight
      gain were not affected by meloxicam treatment compared to placebo.
      Histopathologically, the surface of the ovary of meloxicam-treated females
      appears irregular and dilated due to the presence of different-sized cysts. Some
      of the cystic follicles were retained ova. Further, immunohistochemical stains
      for estrogen and progesterone receptors showed positive staining in granulosa
      cells and the wall of the unruptured follicle. It is concluded that contraceptive
      effect of meloxicam in female rabbits resulted in a failure of follicular
      rupturing.

PMID- 12814820
TI  - Screening for Chlamydia trachomatis in the pharmacy?

PMID- 12814822
TI  - [Rapid diagnosis of streptococcal pharyngitis: what's new?].

PMID- 12814823
TI  - [Anti-retroviral treatment interruptions in HIV-infected adults: causes,
      clinical, immunological and virological consequences].
AB  - INTRODUCTION: This retrospective study analyses causes as well as clinical,
      immunological and virological consequences of antiretroviral treatment
      interruptions (Ti) of more than 30 days in HIV-1 infected adults. METHODS: This
      causes were classified as related to drug toxicity, therapeutic or adherence
      failure. We studied therapeutic regimens before Ti and after treatment
      reinitiation (TR), clinical events related to Ti, CD4 cells and viral loads
      before Ti and at months 3, 6, 9, and 12 after TR. RESULTS: Out of 188 Ti
      analysed, 42.6% were related to therapeutic failure, 33.5% to drug toxicity, and
      23.9% to adherence failure. Eight Aids defining clinical events were reported
      during Ti, in patients with low CD4 cells and high viral load (P < 0.05). Viral
      loads evolution after TR was better if Ti was related to treatment failure (P <
      0.05), was prolonged (P < 0.05), and if CD4 cells were high before Ti and at TR
      (P < 0.05). Median CD4 cells was of 296/mm(3) at month 12 after TR vs 382 before
      Ti. CONCLUSIONS: Ti consequences are strongly related to CD4 cells, which
      decrease sharply during Ti, increasing Aids defining events probability.
      Prospective randomised clinical studies are needed to define usefulness of Ti.

PMID- 12814824
TI  - [Pheochromocytoma in internal medicine: distinctive features and place of 123I
      MIBG scintigraphy].
AB  - PURPOSE: Pheochromocytoma diagnosis uses the localization of the tumour,
      particularly thanks to MIBG scintigraphy. The aims of this study were to evaluate
      the sensibility and specificity of this exam, his opportunity towards clinical
      and biological profile of patients with pheochromocytoma suspicion in Internal
      Medicine and towards others techniques of imaging. We tried to define the most
      effective and least expensive approach of pheochromocytoma diagnosis. METHOD:
      This study was carried out over 15 years period on 80 patients in Internal
      Medicine who underwent 123I MIBG scintigraphy for pheochromocytoma suspicion.
      RESULTS: Among the 80 patients who underwent 123I MIBG scintigraphy, only 18
      suffered from a pheochromocytoma. A very few symptoms were specific, like the
      triad "headaches, sweating, palpitations" whose onlyone third of patients was
      concerned by. The diagnosis approach carried on with urine catecholamine
      measurement, who was specific when metanephrines were increased whatever their
      levels and when normetanephrines were higher or equal than 1,5 time the norme.
      Then, abdominal CT or MRI scanning and 123I MIBG scintigraphy were performed for
      localization of the tumor. The sensibility of scintigraphy was 83%, its
      specificity was 89%. That is comparable with other studies about 131I MIBG.
      CONCLUSION: Prescription of MIBG scintigraphy in Internal Medicine appears to be
      excessive: 77,5% of patients don't have a pheochromocytoma. It is related to the
      lack of specific symptoms, the wrong positives in urine normetanephrines
      measurement and the discovery of incidentaloms by CT scanning. The scintigraphy
      should be used like a topographic and not a diagnosis exam.

PMID- 12814825
TI  - [High levels of factor VIIIc and risk of venous thrombosis: critical analysis of
      case-control studies].
AB  - INTRODUCTION: Deep venous thrombosis is a frequent and potentially serious
      disease. Its causes are multifactorial, associating facilitating circumstances
      and genetic or acquired coagulation abnormalities. Genetic currently well known
      abnormalities are quantitative deficiencies of some natural anticoagulants
      (proteins C and S, antithrombin), and mutations of V and II (G20210-A) genes. The
      Leiden group has recently shown that the elevation of some coagulation factors
      level could also constitute a risk factor for deep venous thrombosis. CURRENT
      KNOWLEDGE AND KEY POINTS: Elevation of factor VIIIc is associated with a higher
      risk for thrombosis than in the general population but the threshold for
      normality of this factor is difficult to define. It is a probable constitutional
      abnormality whose prevalence in the general population vary from 6 to 36%. Risks
      of deep venous thrombosis associated to this factor elevation is more elevated in
      patients who have this anomaly (odds ratios vary from 2,2 to 10,3) (95% CI).
      FUTURE AND PROJECTS: The frequency of this anomaly and its association with a
      high risk for thrombosis are reasons to assess the potential usefulness of
      screening for these anomalies in patients who had thrombosis or in their family.
      The probable genetic origin of these anomalies has to be confirmed by other
      studies.

PMID- 12814826
TI  - [Epidermal growth factor inhibitors].
AB  - PURPOSE: Tyrosine kinases are implicated in the normal cellular proliferation and
      in malignant transformation. Among the tyrosine kinase receptors, one of best
      described is the Epidermal Growth Factor Receptor (EGFR), which is widely
      expressed in particular in epithelial cells and in many human carcinomas. CURRENT
      KNOWLEDGE AND KEY POINTS: Compounds have been developed that target either the
      extracellular ligand-binding region of EGFR (Cetuximab) or the intracellular
      tyrosine kinase ATP-binding (Iressa), Tarceva. Phase I studies showed that these
      molecules have a favorable pharmacokinetic and pharmacodynamic profile, with
      excellent tolerance and easy administration. Phase II and III studies are
      currently testing their efficacy. FUTURE PROSPECTS AND PROJECTS: Preliminary
      results show interesting activity in different tumors, alone or in combination
      with either chemotherapy or radiotherapy. If these results are confirmed in
      larger trials including a high number of patients, these agents might be very
      useful in combination with chemotherapy, radiotherapy or other biological
      targeting agents such as cellular cycle inhibitors or antiangiogenics.

PMID- 12814827
TI  - [Steroid induced osteoporosis: prevention and treatment].
AB  - PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent
      complication of long-term corticosteroid therapy, and the most frequent cause of
      secondary osteoporosis. New data from biological, epidemiological and therapeutic
      studies provide basis for optimal management of this bone disease. MAIN POINTS:
      Corticosteroids are responsible for both quantitative and qualitative deleterious
      effects on bone, through their effect on bone cells, mainly on osteoblasts (with
      both a decrease in osteoblast activity and an increase in apoptosis).
      Epidemiological studies have shown an increased risk of fractures related to CIO,
      even for low doses, and during the first 6 months of treatment. Relative risk is
      1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral
      density, measured by dual-energy X-ray absorptiometry, is decreased at spine and
      hip; the risk of fracture is higher in CIO as compared to post-menopausal
      osteoporosis, for a similar bone density. Prevention of CIO needs the use of the
      minimal efficacious dose, and treatment of calcium, vitamin D and gonadal
      hormones insufficiencies. Patients at risk of fracture, as post-menopausal women
      with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be
      possible to reduce the fracture risk in patients on long-term corticosteroid
      therapy.

PMID- 12814828
TI  - [Disseminated and central nervous system Histoplasma capsulatum infection
      mimicking neoplasm: difficulties in diagnosis, failure in management].
AB  - INTRODUCTION: Infection with Histoplasma capsulatum (Hc) is a rare importing
      disease in metropolitan France, the most often minor but sometimes letal in its
      spread form. EXEGESIS: A 58 years old French man, HIV seronegative, was admitted
      for an alteration of its general condition, disorder and buccal ulcerations. He
      had a prostate cancer history and came back in France after 17 years in Central
      Africa. The imaging showed numerous cerebral nodes, a bilateral adrenal tumor,
      and pulmonary calcifications. Histoplasmosis diagnosis has been done after
      neurosurgical cerebral biopsy which displayed characteristic Hc. The sick man
      died 4 months later with multivisceral failures, in spite of amphotericine B
      treatment followed by oral then intraveinous itraconazole. CONCLUSION: Even in an
      old tropical residence, ones can be able to conjure up a deep exotic fungal
      infection, and most specifically Hc histoplasmosis, in front of meaningful
      multivisceral lesions. Disseminated histoplasmosis (HD) with neurological
      location is misleading, mimicking tuberculosis or cancer. In order to obtain
      formal mycological evidence, ones have to make adapted biopsies. Antifungal
      agents must take into account medicinal interaction. Therefore, prognosis is bad,
      according to inoculum, immunodeficiency, age of disease and diagnosis delay.

PMID- 12814829
TI  - [Eccrine squamous syringometaplasia and cytomegalovirus infection].
AB  - BACKGROUND: Eccrine squamous syringometaplasia has been reported in some cases as
      an Herpeviridae complication. We report a case of eccrine squamous
      syringometaplasia associated with a severe cytomegalovirus infection in an
      immunocompromised patient, and we discuss about potential viral or drug
      triggering factors. METHODS: A 22 years-old man was hospitalized in an intensive
      care unit for rejection of a renal graft associated with a disseminated
      cytomegalovirus infection. A papular and papulopustular eruption appeared on the
      trunk and the limbs. RESULTS: Histological examination of a skin sample showed
      eccrine squamous syringometaplasia, with evidence of cytomegalovirus genomic
      sequences using PCR. Two weeks later, the patient developed toxic epidermal
      necrolysis, with fatal issue. CONCLUSIONS: Eccrine squamous syringometaplasia is
      a rare condition, without specific clinical features. Numerous local affections
      have been reported to induce eccrine syringometaplasia (ulcer, scar, pyoderma
      gangrenosum, drug injection.), drugs (cytotoxic agents, non steroidal anti
      inflammatory therapies) and in cases of infection due to cytomegalovirus or
      herpes simplex virus. The potential implication of cytomegalovirus or foscarnet
      as triggering factors in our case is discussed. This observation and other
      similar reported cases lead to the conclusion that eccrine squamous
      syringometaplasia may be an underestimated complication of cytomegalovirus
      infections in immunocompromised patients.

PMID- 12814830
TI  - [Pancytopenia and macular rash in a woman with a history of breast cancer].

PMID- 12814831
TI  - [Cell therapy to treat heart failure].
AB  - INTRODUCTION: Systolic heart failure is mainly due to a decreased left
      ventricular systolic function after myocardial infarction. Despite significant
      improvements in medical management of heart failure, the prognostic remains poor,
      with a 5-years survival only of 30%. PURPOSE: Current treatments are only able to
      delay progression toward end-stage heart failure. Heart transplantation is
      accessible only for selected patients. Thus, in the context of post-myocardial
      infarction, cell therapy appears to be a new original technique, available for
      the majority of patients and potentially non-invasive. CONCLUSION: After
      promising results in experimental models, a phase I clinical trial has been
      conducted in France, showing the feasibility of intracardiac autologous skeletal
      myoblast implantation. Other studies in Europe and USA are currently testing a
      variety of cells and delivery systems. A phase II-trial will begin in France.

PMID- 12814832
TI  - [Association of immunologic thrombocytopenia and thrombotic thrombocytopenia
      purpura].

PMID- 12814833
TI  - [Report of the Third International Conference on familial Mediterranean fever and
      hereditary inflammatory diseases. La Grand Motte, September 2002].

PMID- 12814834
TI  - [10th International Congress on Antiphospholipid Antibodies. Taormina, Sicily,
      Italy, September 29-October 3, 2002].

PMID- 12814835
TI  - Effective expression of the green fluorescent fusion proteins in cultured Aplysia
      neurons.
AB  - The green fluorescent fusion protein and its isoforms are extensively used to
      monitor gene expression, protein localisation and their dynamics in relations to
      fundamental cellular processes. However, it has not yet been effectively applied
      to Aplysia neurons that serve as a powerful model to study the mechanisms
      underlying neuroplasticity. We report here the development of a procedure
      combining in vitro transcription of mRNA encoding fluorescent-tagged proteins and
      its subsequent injection into the cytoplasm to image, in real-time, protein
      dynamics in cultured Aplysia neurones. To illustrate the efficiency of the
      procedure we report here the visualisation of actin, microtubules and vesicle
      trafficking. The results presented here introduce a reliable and effective method
      to express green fluorescent protein (GFP) fusion proteins in cultured Aplysia
      neurons.

PMID- 12814836
TI  - A micromachined silicon multielectrode for multiunit recording.
AB  - A 16-channel multielectrode was used to record propagating action potentials from
      multiple units in the ventral nerve cord of the cricket Gryllus bimaculatus. The
      multielectrode was fabricated using photolithographic and bulk silicon etching
      techniques. The fabrication differs from standard methods in its use of deep
      reactive ion etching (DRIE) to form the bulk electrode structure. This technique
      enables the fabrication of relatively thick (>100 microm), rigid structures whose
      top surface can have any form of thin film electronics. The multielectrode tested
      in this paper consists of 16 narrow silicon bridges, 150 microm wide and 350
      microm tall, spaced evenly over a centimeter, with passive rectangular gold
      recording sites on the top surface. The nerve cord was placed perpendicularly
      across the bridges. In this geometry, the nerve spans a 350 microm deep, 450
      microm wide trench between each recording site, permitting adequate isolation of
      recording sites from each other and a platinum ground plane. Spike templates for
      eight neurons were formed using principle component analysis and clustering of
      the concatenated multichannel waveforms. Clean templates were generated from a 40
      s recording of stimulus evoked activity. Conduction velocities ranged from 2.59+/
      0.05 to 4.99+/-0.12 m/s. Two limitations of extracellular electrode arrays are
      the resolution of overlapping spikes and relation of discriminated units to known
      anatomy. The high density, precise positioning, and controlled impedance of
      recording sites achievable in microfabricated devices such as this one will aid
      in overcoming these limitations. The rigid devices fabricated using this process
      offer stable positioning of recording sites over relatively large distances
      (several millimeters) and are suitable for clamping or squeezing of nerve cords.

PMID- 12814837
TI  - Dual-electrode voltammetry of catecholamine transport: simultaneous monitoring of
      uptake and efflux.
AB  - Dual-electrode voltammetry is used to characterize induced efflux of dopamine by
      m-tyramine via the norepinephrine transporter, stably expressed in a LLC-PK(1)
      cell line. A rotating disk electrode measures solely the dopamine oxidation
      current, while a stationary electrode held at a higher potential measures both
      the dopamine and m-tyramine concentrations. The ratio of the rate of dopamine
      efflux to the rate of m-tyramine uptake exhibits a hyperbolic dependence on
      initial dopamine concentration (half-maximal initial concentration of 4 microM)
      and is independent of the concentration of m-tyramine used to induce efflux for
      the two concentrations of tyramine tested (3 and 10 microM). These results are
      consistent with the alternating access model of transport, in which the ratio is
      shown to be independent of the nature of the external substrate used to induce
      efflux. At a representative initial dopamine concentration of 1 microM, the ratio
      of efflux to uptake is approximately 0.15 at the time of external substrate
      addition (zero internal tyramine). The result suggests that at this point, the
      transporter reorients to the external facing configuration without dopamine
      approximately 85% of the time, or expressed differently, seven external substrate
      molecules are taken up, on average, for each one transported outward.

PMID- 12814838
TI  - Quantitative assessment of directed hind limb scratching behavior as a rodent
      itch model.
AB  - Hind limb scratching is used increasingly as an itch model in rodents. Scratching
      is usually quantified as the number of scratching bouts over a 60 min period.
      Since the antipruritic effect of scratching should depend on the total time of
      skin contact, then the duration of scratching bouts and within-bout scratching
      frequency may also be important factors. Therefore, we measured these parameters
      during episodes of scratching directed toward the site (nape of neck) of
      intradermal injection of serotonin in Sprague-Dawley rats. Serotonin elicited
      significantly more scratching bouts than saline. There was a biphasic pattern of
      scratching over time, with peaks at 10-20 and 40-50 min. Although cumulative bout
      duration (2-min intervals) had a similar biphasic distribution, the mean
      individual bout duration (2.1 s) did not change significantly over time. Within
      bout scratching frequency remained constant over time at 8 Hz. The number of
      scratching bouts was suppressed in a dose dependent manner by naltrexone (3 and 5
      mg/kg), while the individual bout duration and the within-bout frequency were not
      significantly different compared with serotonin-evoked scratching without
      naltrexone. These results validate the total number of scratching bouts as an
      indicator of the magnitude of itch-related scratching.

PMID- 12814839
TI  - Evaluation of an improved automated analysis of freezing behaviour in rats and
      its use in trace fear conditioning.
AB  - Pavlovian fear conditioning in rodents often involves the assessment of freezing
      behaviour. Since human-based scoring is labour-intensive and subject to biases,
      several automated methods have been proposed, but few of them have been assessed
      for temporal definition. An accurate method for the automated analysis of
      freezing in rats is presented. It is based on a comparison of contrast from
      successive video images (Learn. Mem. 7 (2000) 58). A major improvement involves
      subtracting a previously recorded image of the empty background from each frame
      before processing. This simple operation greatly improves reliability, since it
      cancels the influence of video noise outside the region of interest in the image
      (the rat), and can also take advantage of the movements of a patterned animal
      over a textured background. The technique is compared with manual scoring and
      with the Anagnostaras method in a trace fear conditioning experiment. The method
      is appropriate to monitor the time course of freezing behaviour. The same system
      with a different threshold can also score locomotor activity. A quantitative
      evaluation of the residual errors inherent to automated methods is attempted.

PMID- 12814840
TI  - Factors affecting the stability of the spike-triggered averaged force in the
      human first dorsal interosseus muscle.
AB  - The reproducibility of motor unit twitches obtained using spike-triggered
      averaging (STA) was examined in the human first dorsal interosseus. For each
      motor unit (30 total) a series of STA twitches was derived using a 30 s averaging
      window. Within each averaging window, eight independent measures characterizing
      motor unit discharge and whole muscle force properties were recorded. These
      included the mean and standard deviation (S.D.) of the interspike interval (ISI),
      the mean and S.D. of pre and post-trigger ISIs used in averaging, and mean and
      S.D. of whole muscle force. To determine the relative importance of the
      independent variables on twitch reproducibility, the variables were used in a
      multiple regression analysis performed on STA twitch peak force (PF), time to
      peak force (TTP) and time of half-force decay (HFD). It was found that PF was
      significantly correlated to the mean and S.D. of whole muscle force, and mean
      post-trigger ISI. TTP was significantly correlated to the S.D. of the post
      trigger ISI and mean whole muscle force while HFD was related to the mean and
      S.D. of the pre-trigger ISI and the mean post-trigger ISI. It was concluded that
      by minimizing whole muscle force variability and the mean and S.D. of acceptable
      ISIs used in the STA process, the reproducibility of the STA twitch is improved.

PMID- 12814841
TI  - A double-lumen intrathecal catheter for studies of modulation of spinal opiate
      tolerance.
AB  - Studies of spinal opioid tolerance frequently employ a spinal infusion model in
      which a single-lumen intrathecal (IT) catheter is connected to an osmotic mini
      pump. We have modified this model by developing a double-lumen catheter system
      that permits continuous delivery of the toleragen to the IT space and allows for
      examination of the effects of concurrent IT drug administration without
      interruption of the ongoing infusion. The catheter is constructed of two pieces
      of PE10 tubing fused to the lumens of a dual-lumen catheter (8 cm) with one PE10
      tube used as an infusion line connected to an osmotic pump and the other for
      injection. The catheter is inserted through the cisterna magna. Most implanted
      rats (66 out of 73) showed full recovery of motor and sensory function without
      detectable neurological deficit. The profile of the tolerance development and the
      response to drug manipulation using the double-lumen catheter are similar to
      previous findings in the spinal infusion model which used a single-lumen
      catheter. Most importantly, we demonstrate that concurrent probe drug testing
      and/or concurrent drug treatment can be achieved without interruption of spinal
      infusion of morphine. Using the double-lumen catheter model expands the range of
      possibility for studies of spinal opiate tolerance and spinal drug delivery.

PMID- 12814842
TI  - Continuous monitoring of intracerebral glutamate levels in awake monkeys using
      microdialysis and enzyme fluorometric detection.
AB  - A technique for continuous on-line detection of glutamate using brain
      microdialysis in awake primates is described. The method is based on an enzymatic
      assay using fluorescence detection of glutamate. The time resolution of the
      continuous fluorescent readout compares favorably with that of most published
      studies, which have used standard high-pressure liquid chromatography detection
      methods for glutamate. Exposure of the system to other amino acids (GABA,
      aspartate, glutamine, ascorbate, taurine, valine, alanine, and D-glutamate)
      revealed that this method is highly specific for L-glutamate. In vitro, the
      system detects reliably glutamate levels as low as 0.5 micromol/l. In vivo
      testing in the striatum of Rhesus macaques showed that glutamate levels were
      enhanced after reverse microdialysis with a glutamate uptake blocker. Stimulation
      with high potassium increased substantially the levels of glutamate, an effect
      that was calcium-dependent. Glutamate levels were also increased when the
      microdialysis solution contained the blocker of voltage-gated potassium channels,
      4-aminopyridine. This technique effectively detects short-term changes in
      glutamate levels evoked by physiologic or pharmacologic manipulations in the
      primate brain.

PMID- 12814843
TI  - Comparison of microdialysis and push-pull perfusion for retrieval of serotonin
      and norepinephrine in the spinal cord dorsal horn.
AB  - Both push-pull and microdialysis methods are utilized to measure norepinephrine
      and serotonin in the dorsal horn of the spinal cord. This experiment was designed
      to determine which technique is better for measurement of norepinephrine and
      serotonin in the spinal cord and also to determine if the samples are best
      collected with or without perchloric acid. Sample stability and an assay
      validation for precision, limit of quantification, and limit of detection were
      also performed. Push-pull or microdialysis catheters were placed transversely
      through the dorsal horn and the catheter was perfused with artificial
      cerebrospinal fluid. Noxious pinch (20 s/min for 10 min) was used to evoke a
      change in the concentration of catecholamines. Samples were collected before,
      during and after pinch. No basal concentrations of epinephrine and serotonin were
      found with microdialysis. Although basal concentrations of norepinephrine were
      measured by microdialysis, there was no change in response to noxious pinch. The
      push-pull technique coupled with collection of samples without perchloric acid
      showed that significant increases in serotonin and norepinephrine are measurable
      in response to noxious pinch. In contrast, when samples were collected with
      perchloric acid present there was no change in serotonin or norepinephrine in
      response to pinch. The stability of catecholamines is greatly affected by
      perchloric acid such that there is a near complete loss of ability to detect
      serotonin and norepinephrine by 24 h in samples collected by push-pull. In
      contrast, samples collected without perchloric acid showed only a 20% reduction
      in concentration by 24 h. Even without perchloric acid, by 1 wk there was a 50%
      or greater loss in the concentrations of norepinephrine in push-pull samples.
      Thus, to measure changes in catecholamines in the dorsal horn, push-pull
      collected without perchloric provides measurable, reliable and valid results if
      analyzed by high performance liquid chromatography within 24 h.

PMID- 12814844
TI  - Precise placement of multiple electrodes into functionally predefined cortical
      locations.
AB  - Current research on topics such as effective connectivity, neuronal coding
      strategy or signal propagation in the central nervous system requires
      simultaneous recordings from multiple sites within functionally grouped but
      topologically distributed neuronal clusters. We have addressed this issue by
      characterization of the cortical functional architecture using optical imaging of
      intrinsic signals (OI) and subsequent placement of multiple, individually
      adjustable electrodes into pre-selected domains. In order to achieve maximum
      precision and flexibility for the positioning of electrodes, a plastic cylinder
      containing channels of an extremely high aspect ratio (density >20
      channels/mm(2)) was fixed above the cortex and individual channel positions were
      superimposed onto the functional maps of orientation columns obtained previously
      with OI. Subsequently, channels corresponding to the desired locations in the
      functional map were used as guide tubes for electrode insertion. The spatial
      precision of this approach was in the range of 100 microm and experiments in cat
      primary visual cortex revealed a close correlation between the desired and the
      actually recorded orientation preferences of the targeted columns. The method is
      applicable to all cortical areas in which OI is feasible and offers a high degree
      of flexibility with respect to the number and geometry of applicable probes. It
      is, thus, an excellent tool for studying distributed codes and interactions
      between multiple predefined recording sites.

PMID- 12814845
TI  - A new transparent multi-unit recording array system fabricated by in-house
      laboratory technology.
AB  - A new recording array system has been developed to record multi-unit activity in
      rabbit retina. The array consists of individually laid down layers of carbon
      fiber or tungsten microelectrodes whose center-center spacing can be made less
      than 100 microm. The array and associated electronics can be constructed by
      technology typically found in most electrophysiology laboratories. The array is
      mostly transparent, so that visual stimuli and microscopic examination can take
      place through it. The array can be manipulated much like a single electrode, and
      thus can be used to record from multiple tissue sites. Arrays as large as 32
      elements have been used, with success rates of about 50% per electrode, with some
      electrodes picking up more than one cell. Stable recordings have been held for up
      to 6 h from groups of ganglion cells in an isolated eyecup preparation. These
      multi-electrode arrays have been used repeatedly in experiments for several
      months without any obvious degradation in recording quality. Although the arrays
      are hand-made, their layered method of assembly allows as many as 32 elements to
      be assembled.

PMID- 12814846
TI  - The significance of coping as a therapeutic variable for the outcome of
      psychological therapy in schizophrenia.
AB  - Although there is now strong evidence confirming the efficacy of psychological
      therapies in schizophrenia, the therapeutic processes which they activate remain
      widely unknown. In order to effectively implement them in clinical practice,
      identification of these processes is essential. In a controlled study, the
      efficacy of a coping-oriented therapy approach for schizophrenia patients was
      tested. Furthermore, the study aimed at establishing preliminary hypotheses on
      the therapeutically relevant factors. Treatment effects were found in the
      prominence of psychopathology, the extent of cognizance of the disorder, and the
      level of social functioning. Moreover, a better psychopathological and social
      outcome as measured 12 and 18 months after completion of therapy was best
      predicted by the patients' mastery of active, problem-focused coping strategies
      immediately after completion of therapy. The findings underscore the clinical
      relevance of specific coping styles and corroborate the appropriateness of
      focusing on aspects of coping behavior in psychological interventions for
      schizophrenia patients.

PMID- 12814847
TI  - Depression and anxiety in coronary artery bypass grafting patients.
AB  - PURPOSE: Heart surgery is a factor triggering off specific emotional and
      physiological responses of a patient. In spite of positive somatic effects of
      surgery, depression and anxiety can persist or appear for the first time after
      the operation worsening the patient's psychosocial functioning and quality of
      life. The aim of this study is to offer a prospective view on the incidence and
      course of self-reported depression and anxiety in coronary artery bypass graft
      (CABG) patients. SUBJECT AND METHODS: After informed consent, 53 patients who
      submitted to CABG were examined a few days before and after the operation and 3
      months after CABG. They completed the Spielberger Anxiety Questionnaire and Beck
      Depression Inventory. RESULTS: Approximately 55% of the patients had high a level
      of anxiety preoperatively. Shortly after the surgery, 34% of patients and after 3
      months 32% of them had clinically relevant level of anxiety. Thirty-two percent
      of patients before the surgery, 28% immediately after CABG and 26% at follow-up
      were depressed. CONCLUSIONS: High preoperative depression, state and trait
      anxiety scores appear to be predictors of postoperative psychological outcome.
      Preoperative assessment can identify patients at risk for clinical levels of
      postoperative anxiety and depression. Psychological preventive counseling and
      psychiatric intervention can reduce patients' emotional distress, medical and
      economic costs.

PMID- 12814848
TI  - The relevance of suicidal behaviour in jail and prison suicides.
AB  - PURPOSE: Suicide rates in correctional institutions have been increasing during
      the last decades. There has been little interest in whether suicidal ideation and
      intent has been documented by non-medical prison staff (reports of attempted
      suicide, suicide threats, self-harm), and whether these signs of suicidality had
      the consequence of adequate intervention efforts. METHODS: The personal files of
      inmates who committed suicide in the 29 Austrian jails and prisons during the
      last 25 years (1975-1999) were included. We analysed personal characteristics,
      criminological data, circumstances of custody and information about psychiatric
      disorders and treatment. RESULTS: Of a total of 250 suicides, 220 personal files
      were available and included. Suicide attempts were known in 50% of all suicides
      and 37% had expressed suicidality. In >20%, non-medical staff had documented
      signs of suicidality, but no further preventive action (e.g. referral to
      psychiatric care) had taken place. CONCLUSION: Signs of suicidality play an
      important role in vulnerability profiles for jail and prison suicides and should
      have the minimal consequence of further psychiatric care.

PMID- 12814849
TI  - The dexamethasone suppression test and CSF-5-HIAA in relation to suicidality and
      depression in suicide attempters.
AB  - This study tested suicidality in relation to cerebrospinal fluid (CSF) 5
      hydroxyindoleacetic acid (5-HIAA) and the dexamethasone suppression test.
      Patients with nonsuppression of cortisol had the highest scores of the Suicide
      Assessment Scale (SUAS) and the Montgomery Asberg Depression Rating Scale
      (MADRS), respectively (P < 0.05; P < 0.01). The results persisted when analysed
      for covariance with CSF-5-HIAA. We have previously noted an elevated suicide risk
      in suicide attempters with high SUAS-scores, why a large part of nonsuppressors
      may be at high risk for future suicide.

PMID- 12814850
TI  - Prediction of the occurrence and intensity of post-traumatic stress disorder in
      victims 32 months after bomb attack.
AB  - INTRODUCTION: Our objective was to identify factors that predict occurrence and
      severity of post-traumatic stress disorder (PTSD) after a terrorism attack.
      POPULATION: We evaluated 32 victims of a bomb attack in a Paris subway in
      December 1996 at 6 and 32 months. METHOD: Sociodemographic characteristics,
      clinical data and physical injuries were used to predict PTSD occurrence and
      severity in 32 victims. The Watson's PTSD Inventory (PTSD-I) and the Impact of
      Event Scale (IES) by Horowitz were used to evaluate occurrence and severity of
      PTSD, respectively. RESULTS: Thirty-nine percent of participants met PTSD
      criteria at 6 months, 25% still had PTSD at 32 months. Women had PTSD 32 months
      after the bomb attack more frequently than men. Employment predicted PTSD
      severity at 32 months. PTSD scores assessed by PTSD-I at 6 months were
      significantly and positively associated with IES scores at 32-month follow-up (r
      = 0.55, P = 0.004). Psychotropic drug use before the bomb attack significantly
      predicted PTSD occurrence and severity at 6 and 32 months. In a linear regression
      model, physical injuries, employment status and psychotropic drug use before the
      bomb attack were independent predictors of severity of PTSD at 32 months.
      CONCLUSIONS: Bomb attack exposure resulted in persisting PTSD in a significant
      proportion of victims; the severity was predicted at 32 months by physical
      injuries and psychotropic drug use before the terrorism attack and by the PTSD
      score few months after the bomb attack.

PMID- 12814851
TI  - Susceptibility to neuroleptic-induced parkinsonism--age and increased substantia
      nigra echogenicity as putative risk factors.
AB  - OBJECTIVE: Patients treated by neuroleptics often develop neuroleptic-induced
      parkinsonism (NIP) to a varying extent. The reasons for this are discussed
      controversially in the literature. Previous transcranial sonography (TCS)
      findings of the substantia nigra (SN) in patients with idiopathic Parkinson's
      disease suggest a correlation of echogenicity with nigrostriatal dysfunction.
      METHOD: One hundred psychiatric patients receiving neuroleptics were included.
      They underwent clinical examination for NIP (Simpson and Angus-scale) and,
      independently, TCS of the SN. History of smoking habits and medication were taken
      from the patient's chart. RESULTS: We found a significant positive association of
      the prevalence of NIP with age (P < 0.01) and the echogenic area of the SN (P <
      0.05). Neither type nor dosage of the neuroleptics was found to have any
      significant impact on the occurrence of NIP. Smokers displayed lower prevalence
      of NIP (P < 0.05) and lower EPS scores (P < 0.01). CONCLUSIONS: These findings
      suggest that age and increased size of SN echogenicity are possible risk factors
      for NIP. In contrast, smoking seems to have a certain protecting effect.

PMID- 12814852
TI  - A method for controlling for a high placebo response rate in a comparison of
      venlafaxine XR and diazepam in the short-term treatment of patients with
      generalised anxiety disorder.
AB  - This randomised, double-blind, placebo-controlled study compared the efficacy of
      venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment
      period in 540 non-depressed outpatients with generalised anxiety disorder (GAD).
      At week 8, significant improvements from baseline were observed in the
      venlafaxine XR, diazepam and placebo groups. Although these improvements were
      higher in the first two groups than in the placebo group for each of the primary
      efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A
      psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub
      scale and Clinical Global Impression (CGI) improvement), there were no
      statistically significant differences between groups. These non-positive results
      were thought to be due to the very high placebo response observed in some
      centres. To understand the variability of the study, a secondary preplanned
      analysis was performed. This involved sub-dividing the study centres according to
      their ability to detect a two-point mean difference between diazepam and placebo
      at week 8 on the HAM-A total score. Centres able to show such a difference were
      termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR
      treated patients from verum-sensitive centres were significantly greater than in
      placebo on each of the primary efficacy measures (P </= 0.05). This suggests that
      those centres able to detect an anxiolytic effect of diazepam were also able to
      detect an anxiolytic effect of venlafaxine XR. Significant differences in
      baseline demographics, rates of adverse event reporting and rates of patient
      discontinuations were noted between patients enrolled at verum-sensitive and
      verum-insensitive sites. These results reflect the importance of study centre
      selection in accurately determining efficacy in placebo-controlled trials.

PMID- 12814853
TI  - Statistical considerations about the question of a selection of discriminating
      centres in the analysis of clinical trial. In response to the paper: "A method
      for controlling for a high response rate in a comparison of venlafaxine XR and
      diazepan in the short-term treatment of patients with generalised anxiety
      disorder".

PMID- 12814854
TI  - A psychopathological study of a group of schizophrenic patients after attempting
      suicide. Are there two different clinical subtypes?
AB  - Fifty-six schizophrenic patients at the moment of their suicidal attempt were
      compared to a control group of 60 patients. Schizophrenic suicidal attempters
      showed an identifiable clinical profile at the acute phase. Two main groups could
      be differentiated in regard to their reasons (depressive or psychotic) for
      attempting suicide.

PMID- 12814855
TI  - Factors and motives associated with drop-out in an ambulatory service for
      patients with psychotic disorders.
AB  - The aim is to study motives and factors associated with treatment drop-out in an
      ambulatory psychiatric service, which integrates medical, social, familial and
      rehabilitation treatments. Only 9% of the psychotic patients dropped out, whose
      motives were non-compliance with medication and unawareness of illness, and the
      associated factors were comorbidity of substance abuse, social isolation and male
      gender.

PMID- 12814856
TI  - Induction of mania by rTMS: report of two cases.
AB  - There is some evidence that repetitive transcranial magnetic stimulation (rTMS)
      may be effective in treating depression. Using an intensive methodology of rTMS
      in two drug-resistant patients, we observed a good antidepressant effect, but
      also, induction of manic symptoms.

PMID- 12814857
TI  - Re. Sinistrality in subtypes of schizophrenia.

PMID- 12814858
TI  - Genome scale mapping of brain gene expression.
AB  - Two new approaches, voxelation and gene expression tomography (GET), permit
      multiplex acquisition of gene expression patterns in the brain. Both methods
      result in volumetric images of gene expression analogous to those produced in
      biomedical imaging systems. Voxelation employs analysis of spatially registered
      cubes from the brain, whereas GET entails analysis of parallel slices obtained by
      rotation about multiple axes. These methods have been used to investigate
      neurologic diseases and their models in both humans and mice. The results of
      these studies are discussed, as is the future of high-throughput gene expression
      mapping in the brain.

PMID- 12814859
TI  - Loss and altered spatial distribution of oligodendrocytes in the superior frontal
      gyrus in schizophrenia.
AB  - BACKGROUND: Brain imaging, molecular genetic, and ultrastructural evidence
      indicate the existence of pathologic alterations in the cortical and subcortical
      white matter of schizophrenic patients. METHODS: We performed a stereologic
      analysis of numbers, densities, and spatial distribution of oligodendrocytes in
      layer III and in the gyral white matter of Brodmann's area 9 in the superior
      frontal gyrus to assess whether these cells are affected in schizophrenia. Counts
      were obtained on Nissl-stained materials and on sections immunolabeled for the
      oligodendrocyte marker 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in
      seven schizophrenic and seven age-matched control cases. RESULTS: A 28% decrease
      in total numbers (or densities) of cortical layer III oligodendrocytes and a 27%
      decrease in the white matter were detected in schizophrenic compared with control
      cases based on CNPase immunostaining. Nissl and CNPase immunohistochemistry
      yielded comparable results. The spatial distribution of oligodendrocytes in area
      9 white matter exhibited a less clustered arrangement in schizophrenic cases.
      CONCLUSIONS: These results suggest a severe pathology of oligodendrocytes in
      schizophrenia and provide a quantitative cellular correlate of the white matter
      changes observed by brain imaging in vivo, showing reduced fractional anisotropy
      in schizophrenia. The data support recent evidence that several genes encoding
      myelin-related proteins consistently exhibit reduced expression in schizophrenia.

PMID- 12814860
TI  - Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex
      in major depressive disorder, bipolar disorder, and schizophrenia: evidence for
      decreased neuronal somal size and increased neuronal density.
AB  - BACKGROUND: Abnormalities of cortical neuronal organization and reductions in
      neuronal somal size have been reported in schizophrenia. The purpose of this
      investigation was to assess patterns of neuronal and glial distribution in the
      anterior cingulate cortex (ACC) in major depressive disorder (MDD),
      schizophrenia, bipolar disorder (BPD), and normal control subjects (15 subjects
      per group). METHODS: Estimates for neuronal somal and glial nuclear size and
      density were obtained. We employed two-dimensional morphometric analysis to
      examine the location of neurons and glia in a 1000-microm-wide strip of cortex.
      RESULTS: A decreased clustering of neurons was seen in BPD (p =.001). No other
      group differences were observed in the clustering of neurons, glia, or of neurons
      about glia. Neuronal somal size was reduced in layer 5 in schizophrenia (18%, p
      =.001), BPD (16%, p <.001), and MDD (9%, p =.01). Neuronal density was increased
      in layer 6 in BPD (63%, p =.004) and schizophrenia (61%, p =.006) and in layer 5
      in MDD (24%, p =.018) and schizophrenia (33%, p =.003). CONCLUSIONS: The results
      of this study indicate that reduced neuronal somal size and increased neuronal
      density in cortical layers 5 and 6 of the ACC may be key features of
      schizophrenia, MDD, and BPD.

PMID- 12814861
TI  - Right lateral fusiform gyrus dysfunction during facial information processing in
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia exhibit facial information processing
      deficits that likely contribute to their social dysfunction. Whether the deficits
      involve facial affect and/or identity processing or result from other cognitive
      abnormalities in schizophrenia remains controversial, and a brain dysfunction
      specifically related to them has never been reported. If such dysfunction
      existed, it should be consistently observed across groups of patients and during
      performance of different facial information processing tasks, independently of
      whether such tasks demand working memory (WM), semantic, or other cognitive
      processes. We hypothesized that the right lateral fusiform gyrus (rLFG), one of
      several human brain areas involved in facial information processing, would
      consistently show activation abnormalities during both facial affect and identity
      discrimination in schizophrenia. METHODS: We used functional magnetic resonance
      imaging to measure brain activation in two groups of six chronic, stable
      schizophrenic outpatients and two of six age- and gender-matched healthy
      controls. One group of patients and one of controls performed facial affect-with
      or without semantic processing-and identity discrimination tasks, and the other
      two groups WM tasks with facial expression cues and varying attentional demands.
      RESULTS: Patients from either group failed to activate the rLFG when compared to
      controls in any task. Other activation abnormalities were task-specific (i.e.,
      seen only during performance of one set of tasks) and not consistently observed
      in both groups of patients, and thus could not be directly and solely linked to
      facial information discrimination. CONCLUSIONS: These results indicate a specific
      rLFG dysfunction during early facial information--identity or affect--processing,
      independent from other cognitive deficits, in schizophrenia.

PMID- 12814862
TI  - Visual masking as a probe for abnormal gamma range activity in schizophrenia.
AB  - BACKGROUND: Visual masking procedures assess very early stages of visual
      perception. Patients with schizophrenia consistently show deficits on visual
      masking tasks, and these deficits likely reflect vulnerability to schizophrenia.
      We conducted two experiments to determine whether visual masking procedures can
      reveal underlying abnormalities in gamma range oscillations in schizophrenia.
      METHODS: In the first experiment, we conducted nonlinear modeling of visual
      masking performance data from 89 male schizophrenic patients and 20 male
      comparison subjects. In the second experiment, electrophysiological recordings of
      event-related gamma activity were taken during a visual masking task in a subset
      of eight patients and seven control subjects. RESULTS: In the first experiment,
      nonlinear modeling of the performance data revealed evidence of oscillations in
      the gamma range (30 and 35 Hz) for the comparison group but not patients. In the
      second experiment, the comparison group, but not the patients, showed a burst of
      gamma range activity 200-400 msec following target presentation. The difference
      between patients and comparison subjects in this time period was significant (p
      <.05). CONCLUSIONS: Visual masking procedures can serve as a probe for underlying
      gamma range activity, which appears to be aberrant in schizophrenia. Perceptual
      problems in schizophrenia may, at least in part, be due to a failure to establish
      and/or maintain gamma range oscillations.

PMID- 12814863
TI  - How specific are deficits in mismatch negativity generation to schizophrenia?
AB  - BACKGROUND: Mismatch negativity (MMN) is an auditory event-related potential that
      provides an index of auditory sensory memory. Deficits in MMN generation have
      been repeatedly demonstrated in chronic schizophrenia. Their specificity to
      schizophrenia has not been established. METHODS: Mismatch negativity to both
      duration and frequency deviants was investigated in gender- and age-matched
      patients with schizophrenia or schizoaffective disorder (n = 26), bipolar
      disorder (n = 16), or major depression (n = 22) and healthy control subjects (n =
      25). RESULTS: Only patients with schizophrenia demonstrated significantly smaller
      mean MMN than did healthy control subjects. Detailed analyses showed
      significantly smaller MMN to both duration and frequency deviants in patients
      with schizophrenia than in healthy control subjects; however, the reduction of
      frequency MMN in patients with schizophrenia was not significant in the
      comparison across all groups. Mismatch negativity topography did not differ among
      groups. No consistent correlations with clinical, psychopathologic, or treatment
      variables were observed. CONCLUSIONS: Mismatch negativity deficits, and by
      extension deficits in early cortical auditory information processing, appear to
      be specific to schizophrenia. Animal and human studies implicate dysfunctional N
      methyl-D-aspartate receptor functioning in MMN deficits. Thus MMN deficits may
      become a useful endophenotype to investigate the genetic underpinnings of
      schizophrenia, particularly with regard to the N-methyl-D-aspartate receptor.

PMID- 12814864
TI  - Elevated cerebrospinal fluid SNAP-25 in schizophrenia.
AB  - BACKGROUND: Research suggests an association between abnormal exocytosis and
      schizophrenia. We previously demonstrated increased synaptosomal associated
      protein, 25 kDa (SNAP-25), a member of the exocytotic mechanism, in the
      cerebrospinal fluid (CSF) of schizophrenia subjects. In this study, we explored
      SNAP-25 level and clinical variables in a new group of subjects. METHODS: Twenty
      five haloperidol-treated subjects with chronic schizophrenia and twenty-five
      healthy control subjects participated in the study. Subjects received haloperidol
      treatment for at least 3 months and then had a lumbar puncture (n = 19).
      Medication was replaced by placebo, and the lumbar puncture was repeated (n = 25)
      after 6 weeks or sooner if limited psychotic symptoms occurred. We measured the
      level of SNAP-25 in the CSF and symptoms with the Brief Psychiatric Rating Scale
      (BPRS). RESULTS: In both haloperidol (p =.001) and placebo (p =.001) treatment
      conditions, SNAP-25 was elevated. There was no significant difference in SNAP-25
      level between conditions. We identified significant positive correlations among
      SNAP-25 and the BPRS total score and psychosis and thinking disturbance subscales
      in subjects on haloperidol. CONCLUSIONS: These observations confirm our previous
      report of elevated CSF SNAP-25 and suggest that synaptic pathology may be linked
      with the pathophysiology of schizophrenia.

PMID- 12814865
TI  - N-acetylaspartate and N-Acetylaspartylglutamate deficits in superior temporal
      cortex in schizophrenia and bipolar disorder: a postmortem study.
AB  - BACKGROUND: N-acetylaspartylglutamate is found in neurons and its metabolite N
      acetylaspartate, which can be measured by magnetic resonance spectroscopy, is
      considered a marker of neuronal integrity. Several magnetic resonance
      spectroscopy studies have found evidence of N-acetylaspartate deficits in
      schizophrenia. METHODS: We employed a high-pressure liquid chromatography method
      to determine N-acetylaspartate and N-acetylaspartylglutamate in postmortem brain
      tissues taken from a well-defined series of psychiatric cases. N-acetylaspartate
      and N-acetylaspartylglutamate concentrations were measured in superior temporal
      and frontal cortices of patients with schizophrenia, bipolar disorder, and
      depression and control subjects. RESULTS: N-acetylaspartate was significantly
      decreased below controls in superior temporal cortex in schizophrenia (p <.01)
      and bipolar disorder (p <.01), but no deficits were found in frontal cortex. N
      acetylaspartylglutamate was significantly decreased only in superior temporal
      cortex in schizophrenia. CONCLUSIONS: The results are consistent with evidence of
      superior temporal cortex abnormalities in schizophrenia. The finding in bipolar
      disorder suggests that temporal cortex N-acetylaspartate deficits may be a common
      feature of psychotic disorders.

PMID- 12814866
TI  - Incidence of tardive dyskinesia with typical versus atypical antipsychotics in
      very high risk patients.
AB  - Our aim was to study the risk of developing tardive dyskinesia in highly
      vulnerable patients (i.e., middle-aged and older adults with borderline
      dyskinesia) treated with conventional versus atypical antipsychotics.We examined
      the cumulative incidence of definitive tardive dyskinesia at 1, 3, and 6 months
      during antipsychotic treatment among 240 outpatients at least 45 years of age who
      had borderline tardive dyskinesia at baseline. Patients treated with conventional
      antipsychotics were approximately two times more likely to develop definitive
      tardive dyskinesia during the study period compared with those treated with
      atypical antipsychotics (p <.001). This difference was found despite patients in
      the atypical antipsychotic group being significantly older and having more severe
      extrapyramidal symptoms at baseline than those prescribed typical antipsychotics.
      Among patients at a very high risk for worsening tardive dyskinesia, the use of
      atypical antipsychotics was associated with a significantly lower risk of
      developing definitive tardive dyskinesia compared with conventional
      antipsychotics.

PMID- 12814868
TI  - Exploration of critical parameters for transient retrovirus production.
AB  - The pCL system was developed to aid in the production of retrovirus that encodes
      cytotoxic or cytostatic cDNA's. A principal feature of this system is the
      transient production of virus after co-transfection of the viral and packaging
      vectors in the 293T cell line. This approach obviates the need for selection of
      the producer cells, thus minimizing potential affects of the encoded genes.
      However, the transient nature of this system also creates a number of
      experimental variables. In this study we have examined and optimized elements
      related to the production of the pCL retrovirus. For example, co-transfection of
      the packaging sequence along with the viral vector has been optimized in terms of
      both the total amount of DNA transfected and the relative proportion of each
      plasmid. We have also tested the affect of increased synthesis of viral proteins
      in the producer cells and the kinetics of virus accumulation in the supernatant.
      These findings may be of interest to those who use pCL or any transient packaging
      system in their gene transfer studies. In addition, these studies may aid in the
      validation and development of transient retrovirus production systems for
      clinical applications.

PMID- 12814869
TI  - Immobilization of urease onto chemically modified acrylonitrile copolymer
      membranes.
AB  - Poly (acrylonitrile-methylmethacrylate-sodium vinylsulfonate) membranes were
      subjected to seven different chemical modifications. The amounts of new groups
      incorporated in the membranes with the modifications were determined. Urease was
      covalently immobilized on the modified membranes. Both the amount of bound
      protein and relative activity of immobilized urease were measured. The highest
      activity was found for urease bound to membranes modified with hydroxylammonium
      sulfate (68%) and hydrazinium sulfate (67%). Optimum pH of free urease was
      determined to be 5.8. For positively charged membranes, pH optimum was shifted to
      higher values, while for negatively charged membranes-to lower pH. The charge of
      the matrix affected also the rate of the enzyme reaction. The highest rate was
      measured with urease immobilized on membranes modified with hydroxylammonium
      sulfate and hydrazinium sulfate. The major part of the immobilized enzyme on
      different modified membranes remained stable-only ca. 20% of enzyme activity was
      lost for 4 h at 70 degrees C while the free enzyme was totally inactivated.

PMID- 12814870
TI  - Production and characterization of bioactive recombinant resistin in Escherichia
      coli.
AB  - Type 2 diabetes, characterized by peripheral target tissue resistance to insulin,
      is epidemic in industrialized countries and is strongly associated with obesity.
      The protein hormone, resistin, secreted specifically by the adipose tissues, is
      found to antagonize insulin action upon glucose uptake and may serve as an
      important role between human obesity and insulin resistance. Here, we report the
      production of bioactive recombinant resistin in Escherichia coli. cDNA of
      resistin was obtained by RT-PCR from mRNA of mouse differentiated NIH/3T3-L1
      cells. The cDNA of mature resistin was inserted in the pQE-31 vector and the
      recombinant plasmid was transferred into E. coli JM109. After IPTG induction, the
      rec. resistin found in the inclusion body was dissolved in 6 M guanidine-HCl in
      the presence of 10 mM beta-mercaptoethanol. The His-tag containing protein was
      purified by Ni-NTA column to 95% homogeneity. After a quasi-static-like refolding
      process, the secondary structure of the rec. resistin was elucidated by circular
      dichroism which indicated that the protein was composed of 34.3% alpha-helix,
      8.9% beta-sheet, 23.4% beta-turn, and 31.2% unordered structure. No disulfide
      linked homodimers were formed in SDS-PAGE analysis under non-reducing conditions.
      The rec. resistin showed a dose-dependent antagonizing action against insulin in
      [3H]-2-deoxy-glucose transport in a broad range from 1 ng ml(-1) to 10 microg ml(
      1) of resistin. A suppression of 85% of transport was achieved at the dosage of
      10 microg ml(-1). This result may indicate that the rec. resistin does not need
      to form homodimers to establish its bioactivity. The rec. resistin will be useful
      for exploring the biological functions of this newly discovered hormone.

PMID- 12814871
TI  - Separation and identification of different refolding components.
AB  - A dual-gradient ion-exchange chromatography (IEC) refolding process has been
      successfully applied to renature lysozyme at high concentration. The different
      refolding components were separated by size-exclusion chromatography with low
      concentrations of urea and NaCl added into elution buffer. The hydrodynamic
      characteristics during separation and the hydrophobic properties of these
      components were also tested.

PMID- 12814872
TI  - Kinetic parameters of continuous cultures of Bacillus thermoleovorans sp. A2
      degrading phenol at 65 degrees C.
AB  - In this paper, we report on the kinetics of phenol degradation and cell growth in
      continuous cultures of suspended cells of Bacillus thermoleovorans sp. A2 at 65
      degrees C. A high yield coefficient of Y(x/s)=0.84 g cell dry weight g(-1) phenol
      was measured at a dilution rate of 0.5 h(-1). At the same dilution rate the
      coefficient for maintenance metabolism (m(s)) was determined to be 0.045 g phenol
      g(-1) cell dry weight h(-1). The maximal growth rate (wash-out) determined at a
      phenol inlet concentration of 188 mg l(-1) was 0.9 h(-1). Up to 7 g phenol l(-1)
      per day were degraded in a continuously operated 2-l stirred tank reactor with
      suspended cells (feed concentration 660 mg l(-1)). Additionally, yield
      coefficients for oxygen and ammonium are reported.

PMID- 12814873
TI  - Outdoor production of Phaeodactylum tricornutum biomass in a helical reactor.
AB  - The production of microalga Phaeodactylum tricornutum in an outdoor helical
      reactor was analysed. The influence of temperature, solar irradiance and air flow
      rate on the yield of the culture was evaluated. Biomass productivities up to 1.5
      g l(-1) per day and photosynthetic efficiency up to 14% were obtained by
      maintaining the cultures below 30 degrees C, dissolved oxygen levels less than
      400% Sat. (with respect to air saturated culture) and controlling the cell
      density in order to achieve an average irradiance within the culture below 250
      microE m(-2) s(-1). Under these conditions, the fluorescence parameter, Fv/Fm,
      which reflects the maximal efficiency of PSII photochemistry, remained roughly
      0.6-0.7 and growth rates up to 0.050 h(-1) were achieved. The average irradiance
      and the light/dark cycle frequency, were the variables determining the behaviour
      of the cultures. A hyperbolic relationship between growth rate and biomass
      productivity with the average irradiance was observed, whereas both biomass
      productivity and photosynthetic efficiency linearly increased with the light/dark
      cycle frequencies. Optimum design and operational conditions which maximise the
      production of P. tricornutum biomass in outdoor helical reactors were determined.

PMID- 12814874
TI  - Benefits and limitations of modeling for optimization of Porphyridium cruentum
      cultures in an annular photobioreactor.
AB  - A deterministic Markov process was developed to estimate the efficiency of a
      fully controlled photobioreactor by calculating the growth of the Rhodophyte
      Porphyridium cruentum. It was assumed that microalgal growth, in strictly
      controlled and non-nutrient-limited conditions, is a function of the amount of
      light energy received. The light sources delivered a continuous 206 microE m(-2)
      s(-1) average photon flux density to cultures reaching concentrations of 3 g l(
      1) in batch and 0.7 g l(-1) in chemostat. The concentration time-courses
      calculated compared satisfactorily with measured results for both batch and
      continuous cultures. The quality of simulation in these two cases validated the
      hypotheses made, especially for the linearity of light bioconversion, and allowed
      the model to be used for further exploration of the photobioreactor-operating
      domain. Distribution of the specific growth rate as a function of time and radial
      position was compared for the two simulated cases. The use of an initial batch of
      several days prior to the dilution of a continuous culture proved theoretically
      beneficial for overall production. The influence of the dilution rate and of
      light-path length on surface productivity and concentration at steady state were
      demonstrated.

PMID- 12814875
TI  - Pilot-scale extraction of an intracellular recombinant cutinase from E. coli cell
      homogenate using a thermoseparating aqueous two-phase system.
AB  - A thermoseparating aqueous two-phase system for extraction of a recombinant
      cutinase fusion protein from Escherichia coli homogenate has been scaled up to
      pilot scale. The target protein ZZ-cutinase-(WP)(4) was produced in a fed batch
      process at 500 l to a concentration of 12% of the total protein and at a cell
      concentration of 19.7 g l(-1). After harvest and high-pressure homogenisation a
      first extraction step was performed in an EO(50)PO(50) (50% (w/w) ethylene oxide
      and 50% (w/w) propylene oxide) thermopolymer/amylopectin rich Waxy barley starch
      system. The (WP)(4) tag was used for enhanced target protein partitioning to the
      EO(50)PO(50) phase while the cell debris was collected in the starch phase. A
      second extraction step followed where the recovered EO(50)PO(50) phase from the
      first step was supplemented with a non-ionic detergent (C(12-18)EO(5)) and heated
      to the cloud point (CP) temperature (45 degrees C). One polymer-rich liquid phase
      and one almost pure aqueous phase were formed. The target protein could be
      obtained in a water phase after the thermal phase separation at a total recovery
      over the extraction steps of 71% and a purification factor of 2.5. We were able
      to demonstrate that a disk-stack centrifugal separator could be adapted for rapid
      separation of both primary and thermoseparated phase systems.

PMID- 12814876
TI  - Efficient production of Arthromyces ramosus peroxidase by Aspergillus awamori.
AB  - The heterologous production of Arthromyces ramosus peroxidase (ARP) was analysed
      in the filamentous fungus Aspergillus awamori under control of the inducible
      endoxylanase promoter. Secretion of active ARP was achieved up to 800 mg l(-1) in
      shake flask cultures. Western blot analysis showed that an rARP product of the
      correct molecular weight was produced. In contrast to several other studies about
      heterologous production of heme containing peroxidases, our results suggest that
      in A. awamori no heme limitation exists during overproduction of ARP.

PMID- 12814877
TI  - High-density tissue-like cultivation of JAR choriocarcinoma cells for the in
      vitro production of human xylosyltransferase.
AB  - Human xylosyltransferase is the chain-initiating enzyme involved in the
      biosynthesis of glycosaminoglycans. Large amounts of xylosyltransferase are
      required to study the biochemical properties of the native enzyme. To achieve
      this goal a scale-up of animal cell culture systems was inevitable due to the
      small amounts of the enzyme present in tissues, e.g. only 0.5 microg XT can be
      obtained from a chick embryo. JAR choriocarcinoma cells cultured with 10% fetal
      calf serum were found to secrete xylosyltransferase with relatively high
      activities (1.10 mU l(-1)). To reduce contaminating proteins JAR cells were
      adapted to serum-free conditions. Xylosyltransferase activities up to 0.22 mU l(
      1) were determined in the harvested cell culture supernatant. Scaling-up of JAR
      cell culture in the hybrid hollow fiber bioreactor Tecnomouse resulted in the
      production of 15.8 mU or 270 microg XT in 0.5 l of XT-enriched cell culture
      supernatant using 57 l of serum-free cell culture medium. The XT activity per ml
      harvest solution was 200-280-fold higher in this cell culture supernatant than in
      cell culture flasks. In addition, the specific XT activity of the bioreactor
      product was 6 microU mg(-1) of total protein, which is 2-fold higher than that
      obtained under static culture conditions. This study clearly demonstrates the
      successful high-density, tissue-like cultivation of JAR choriocarcinoma cells in
      a hollow fiber bioreactor resulting in an effective production of native human
      xylosyltransferase.

PMID- 12814878
TI  - Natural attenuation of trichloroethylene in fractured shale bedrock.
AB  - This paper describes one of the first well-documented field examples of natural
      attenuation of trichloroethylene (TCE) in groundwater in a fractured shale
      bedrock. The study was carried out adjacent to a former waste burial site in
      Waste Area Grouping 5 (WAG5) on the Oak Ridge Reservation, Oak Ridge, TN. A
      contaminant plume containing TCE and its daughter products were detected
      downgradient from the buried waste pits, with most of the contamination occurring
      in the upper 6 m of the bedrock. The monitoring well array consists of a 35-m
      long transect of multilevel sampling wells, situated along a line between the
      waste pits and a seep which discharges into a small stream. Concentrations of
      volatile organic carbons (VOCs) were highest in the waste trenches and decreased
      with distance downgradient towards the seep. Sampling wells indicated the
      presence of overlapping plumes of TCE, cis-dichloroethylene (cDCE), vinyl
      chloride (VC), ethylene, ethane, and methane, with the daughter products
      extending further downgradient than the parent (TCE). This type of distribution
      suggests anaerobic biodegradation. Measurements of redox potential at the site
      indicated that iron-reduction, sulfate reduction, and potentially methanogensis
      were occurring and are conducive to dechlorination of TCE. Bacteria enrichment of
      groundwater samples revealed the presence of methanotrophs, methanogens, iron
      reducing bacteria and sulfate-reducing bacteria, all of which have previously
      been implicated in anaerobic biodegradation of TCE. 16S rDNA sequence from DNA
      extracted from two wells were similar to sequences of organisms previously
      implicated in the anaerobic biodegradation of chlorinated solvents. The combined
      data strongly suggest that anaerobic biodegradation of the highly chlorinated
      compounds is occurring. Aerobic biodegradation may also be occurring in
      oxygenated zones, including near a seep where groundwater exits the site, or in
      the upper bedrock during seasonal fluctuations in water table elevation and
      oxygen levels.

PMID- 12814879
TI  - Experimental study and steady-state simulation of biogeochemical processes in
      laboratory columns with aquifer material.
AB  - Packed bed laboratory column experiments were performed to simulate the
      biogeochemical processes resulting from microbially catalyzed oxidation of
      organic matter. These included aerobic respiration, denitrification, and Mn(IV),
      Fe(III) and SO(4) reduction processes. The effects of these reactions on the
      aqueous- and solid-phase geochemistry of the aquifer material were closely
      examined. The data were used to model the development of alkalinity and pH along
      the column. To study the independent development of Fe(III)- and SO(4)-reducing
      environments, two columns were used. One of the columns (column 1) contained
      small enough concentrations of SO(4) in the influent to render the reduction of
      this species unimportant to the geochemical processes in the column. The rate of
      microbially catalyzed reduction of Mn(IV) changed with time as evidenced by the
      variations in the initial rate of Mn(II) production at the head of the column.
      The concentration of Mn in both columns was controlled by the solubility of
      rhodochrosite (MnCO(3(S))). In the column where significant SO(4) reduction took
      place (column 2), the concentration of dissolved Fe(II) was controlled by the
      solubility of FeS. In column 1, where SO(4) reduction was not important, maximum
      dissolved Fe(II) concentrations were controlled by the solubility of siderite
      (FeCO(3(S))). Comparison of solid-phase and aqueous-phase data suggests that
      nearly 20% of the produced Fe(II) precipitates as siderite in column 1. The solid
      phase analysis also indicates that during the course of experiment, approximately
      20% of the total Fe(III) hydroxides and more than 70% of the amorphous Fe(III)
      hydroxides were reduced by dissimilatory iron reduction. The most important sink
      for dissolved S(-II) produced by the enzymatic reduction of SO(4) was its direct
      reaction with solid-phase Fe(III) hydroxides leading initially to the formation
      of FeS. Compared to this pathway, precipitation as FeS did not constitute an
      important sink for S(-II) in column 2. In this column, the total reacted S(-II)
      estimated from the concentration of dissolved sulfur species was in good
      agreement with the produced Cr(II)-reducible sulfur in the solid phase. Solid
      phase analysis of the sulfur species indicated that up to half of the originally
      produced FeS may have possibly transformed to FeS(2).

PMID- 12814880
TI  - Use of tracer tests to evaluate the impact of enhanced-solubilization flushing on
      in-situ biodegradation.
AB  - Tracer tests were conducted to evaluate the effect of a complexing sugar flush
      (CSF) on in-situ biodegradation potential at a site contaminated by jet fuel,
      solvents, and other organic compounds. Technical-grade hydroxypropyl-beta
      cyclodextrin was used during the CSF study, which was conducted in a
      hydraulically isolated cell emplaced in a surficial aquifer. In-situ
      biodegradation potential was assessed with the use of tracer tests, which were
      conducted prior to and immediately following the CSF study. Ethanol, hexanol, and
      benzoate were used as the biodegradable tracers, while bromide was used as a
      nonreactive tracer. The results indicate that the biodegradation of benzoate was
      similar for both tracer tests. Conversely, the biodegradation of ethanol (23%
      increase) and hexanol (41% increase) was greater for the post-CSF tracer test. In
      addition, analysis of core samples collected from within the test cell indicates
      that the population density of aerobic jet-fuel degraders increased in the
      vicinity of the injection wells during the CSF. These results indicate that the
      cyclodextrin flush did not deleteriously affect the indigenous microbial
      community. This study illustrates that tracer tests can be used to evaluate the
      impact of remediation activities on in-situ biodegradation potential.

PMID- 12814881
TI  - Measurement and analysis of non-Fickian dispersion in heterogeneous porous media.
AB  - Contaminant breakthrough behavior in a variety of heterogeneous porous media was
      measured in laboratory experiments, and evaluated in terms of both the classical
      advection-dispersion equation (ADE) and the continuous time random walk (CTRW)
      framework. Heterogeneity can give rise to non-Fickian transport patterns, which
      are distinguished by "anomalous" early arrival and late time tails in
      breakthrough curves. Experiments were conducted in two mid-scale laboratory flow
      cells packed with clean, sieved sand of specified grain sizes. Three sets of
      experiments were performed, using a "homogeneous" packing, a randomly
      heterogeneous packing using sand of two grain sizes, and an exponentially
      correlated structure using sand of three grain sizes. Concentrations of sodium
      chloride tracer were monitored at the inflow reservoir and measured at the
      outflow reservoir. Breakthrough curves were then analyzed by comparison to fitted
      solutions from the ADE and CTRW formulations. In all three systems, including the
      "homogeneous" one, subtle yet measurable differences between Fickian and non
      Fickian transport were observed. Quantitative analysis demonstrated that the CTRW
      theory characterized the full shape of the breakthrough curves far more
      effectively than the ADE.

PMID- 12814882
TI  - Influence of surfactant-facilitated interfacial tension reduction on chlorinated
      solvent migration in porous media: observations and numerical simulation.
AB  - The ability of a multiphase flow model to capture the migration behavior of
      chlorinated solvents under conditions of surfactant-facilitated interfacial
      tension (IFT) reduction is assessed through comparison of model predictions with
      observations from controlled laboratory experiments. Tetrachloroethene (PCE) was
      released in two-dimensional saturated systems, packed with sandy media that
      incorporated rectangular lenses of capillary contrast. Spatially uniform
      interfacial tension conditions were created in the tanks by pre-flushing the
      porous medium with either Milli Q water or an aqueous surfactant solution.
      Experimental observations showed that surfactant-facilitated IFT reductions
      substantially lowered capillary resistance to the vertical downward migration of
      PCE and enabled PCE to enter finer grained, less permeable lenses that were not
      penetrated in the absence of surfactant. An immiscible flow model was used to
      simulate the conditions of the laboratory experiments. Under higher IFT
      conditions (47.5 and 5 dyn/cm), the model could successfully predict the general
      migration behavior of the organic liquid. Model predictions, however, exhibited
      poorer agreement with observed migration pathways under low IFT conditions (0.5
      dyn/cm). In all cases, the predicted PCE distributions were influenced by
      selection of the parametric model for capillary retention and relative
      permeability. Simulated migration rates were more consistent with observed
      behavior when the Brooks-Corey/Burdine model was employed. For low interfacial
      tensions, improved predictions of migration pathways were obtained through grid
      refinement and incorporation of small-scale packing variability. Simulations
      highlight the substantial sensitivity of model predictions to the capillary
      pressure-scaling factor, grid resolution, and small-scale porosity variations at
      interfaces of permeability contrast under reduced IFT conditions.

PMID- 12814883
TI  - Changes in enantiomeric fraction as evidence of natural attenuation of mecoprop
      in a limestone aquifer.
AB  - Natural attenuation of the chiral pesticide mecoprop [2-(2-methyl-4
      chlorophenoxy)propionic acid] has been studied by determining changes in its
      enantiomeric fraction in different redox environments down gradient of a landfill
      in the Lincolnshire Limestone. Previous studies have shown that mecoprop degrades
      predominantly aerobically and that differences in the biological behaviour of the
      two enantiomers will change their relative proportions during biodegradation.
      Originally deposited as a racemic mixture, there has been no change in the
      enantiomeric fraction in the most polluted part of the landfill plume where
      conditions are sulphate reducing/methanogenic. In the nitrate-reducing zone, the
      proportion of (S)-mecoprop increases, suggesting preferential degradation of (R)
      mecoprop; while in the aerobic zone, the proportion of (R)-mecoprop increases,
      suggesting faster degradation of (S)-mecoprop. Mecoprop persistence in the
      confined Lincolnshire Limestone further downdip is explained by inhibition of
      degradation in sulphate-reducing conditions, which develop naturally. Laboratory
      microcosm experiments using up to 10 mg l(-1) of mecoprop confirm these
      inferences and show that under aerobic conditions, (S)-mecoprop and (R)-mecoprop
      degrade with zero-order kinetics at rates of 1.90 and 1.32 mg l(-1) day(-1),
      respectively. Under nitrate-reducing conditions (S)-mecoprop does not degrade,
      but (R)-mecoprop degrades with zero-order kinetics at 0.65 mg l(-1) day(-1) to
      produce a stoichiometric equivalent amount of 4-chloro-2-methylphenol. This
      metabolite only degrades when the (R)-mecoprop has disappeared. The addition of
      nitrate to a dormant iron-reducing microcosm devoid of nitrate stimulated
      anaerobic degradation of (R)-mecoprop after a lag period of 21 days. There was no
      evidence for enantiomeric inversion. The study demonstrates the sensitivity of
      changes in enantiomeric fraction for detecting natural attenuation, and reveals
      subtle differences in mecoprop degradation in different redox environments within
      the Lincolnshire Limestone aquifer.

PMID- 12814884
TI  - Carbon and hydrogen isotope effects during sorption of organic contaminants on
      carbonaceous materials.
AB  - Stable carbon and hydrogen isotopes can be an efficient means to validate
      biodegradation of organic contaminants in groundwater since it results in an
      isotopic fractionation. A prerequisite in applying this method in the field is
      the proof that other processes decreasing the contaminant concentration are
      conservative with respect to isotope effects. In this paper we show for carbon
      isotopes of halogenated hydrocarbon compounds [trichloroethene (TCE), cis
      dichloroethene (c-DCE), vinylchloride (VC)] and carbon and hydrogen isotopes of
      BTEX compounds (benzene, toluene, p-xylene) that no significant fractionation
      occurs during equilibrium sorption onto activated carbon, lignite coke and
      lignite. In general, effects were in the range of the reproducibility limit of
      the analytical instrument (0.5 per thousand for delta13C, and 8 per thousand for
      delta2H). This observation was made for fractions sorbed of less than 5% to more
      than 95%. Also for rate-limited sorption of TCE onto activated carbon, no
      significant fractionation in carbon isotopes could be observed. These findings
      support the assumption that for these classes of compounds, sorption processes in
      aquifer systems are conservative with respect to isotope effects.

PMID- 12814885
TI  - Simulating bioremediation of uranium-contaminated aquifers; uncertainty
      assessment of model parameters.
AB  - Bioremediation of trace metals and radionuclides in groundwater may require the
      manipulation of redox conditions via the injection of a carbon source. For
      example, after nitrate has been reduced, soluble U(VI) can be reduced
      simultaneously with other electron acceptors such as Fe(III) or sulfate to U(IV),
      which may precipitate as a solid (uraninite). To simulate the numerous
      biogeochemical processes that will occur during the bioremediation of trace-metal
      contaminated aquifers, a time-dependent one-dimensional reactive transport model
      has been developed. The model consists of a set of coupled mass balance
      equations, accounting for advection, hydrodynamic dispersion, and a kinetic
      formulation of the biological or chemical transformations affecting an organic
      substrate, electron acceptors, corresponding reduced species, and trace metal
      contaminants of interest, uranium in this study. This set of equations is solved
      numerically, using a finite difference approximation. The redox conditions of the
      domain are characterized by estimating the pE, based on the concentration of the
      dominant terminal electron acceptor and its corresponding reduced species. This
      pE and the concentrations of relevant species are then used by a modified version
      of MINTEQA2, which calculates the speciation/sorption and
      precipitation/dissolution of the species of interest under equilibrium
      conditions. Kinetics of precipitation/dissolution processes are described as
      being proportional to the difference between the actual and calculated
      equilibrium concentration. A global uncertainty assessment, determined by Random
      Sampling High Dimensional Model Representation (RS-HDMR), was performed to attain
      a phenomenological understanding of the origins of output variability and to
      suggest input parameter refinements as well as to provide guidance for field
      experiments to improve the quality of the model predictions. By decomposing the
      model output variance into its different input contributions, RS-HDMR can
      identify the model inputs with the most influence on various model outputs, as
      well as their behavior pattern on the model output. Simulations are performed to
      illustrate the effect of biostimulation on the fate of uranium in a saturated
      aquifer, and to identify the key processes that need to be characterized with the
      highest accuracy prior to designing a uranium bioremediation scheme.

PMID- 12814886
TI  - An ORF2 protein-based ELISA for porcine circovirus type 2 antibodies in post
      weaning multisystemic wasting syndrome.
AB  - Porcine circovirus type 2 (PCV2) plays a crucial role in the pathogenesis of post
      weaning multisystemic wasting syndrome (PMWS) in swine. As PCV2 displays
      significant homology with PCV1 (a non-pathogenic virus) at the nucleotide and
      amino-acid level, a discriminative antigen is needed for specific serological
      diagnosis. The ORF2-encoded capsid protein from PCV2 was used to develop an
      indirect enzyme-linked immunosorbent assay (ELISA). GST-fused capsid protein from
      PCV2 and GST alone (both expressed in recombinant baculovirus-infected cells)
      were used as antigens for serodiagnosis. The specificity of the ELISA for
      detection of PCV2 antibodies was demonstrated in sera from pigs experimentally
      infected with PCV1, PCV2 and other swine viruses. The semi-quantitative nature of
      the test was evaluated versus an immunoperoxidase monolayer assay (IPMA). The
      ELISA was performed on 322 sera from pigs in eight Brittany herds and compared
      with IPMA. The sensitivity (98.2%) and specificity (94.5%) of this test were
      considered suitable for individual serological detection. High PCV2
      seroprevalence was found in sows and pigs at the end of the growth phase (18-19
      weeks) in all eight herds. The seroprevalence in piglets (11-17 weeks) was
      statistically correlated with clinical symptoms of PMWS (93% in affected versus
      54%, in non-affected farms). A cohort study performed in PMWS-free farms showed
      that 57% of piglets exhibited active seroconversion after 13 weeks, indicating
      that PCV2 infection occurred earlier in PMWS-affected piglets.

PMID- 12814887
TI  - Partial sequence of the spike glycoprotein gene of transmissible gastroenteritis
      viruses isolated in Korea.
AB  - The spike (S) glycoprotein of transmissible gastroenteritis virus (TGEV) is the
      predominant inducer of neutralizing antibodies and has been implicated in
      virulence and host cell tropism. In this study, the nucleotide and deduced amino
      acid sequences of the amino terminal half of the S glycoprotein gene of one
      Korean field TGEV strain (133) isolated in 1997 and three Korean field TGEV
      strains (KT2, KT3 and KT4) isolated in 2000 and HKT2 strain, KT2 passaged 104
      times in ST cells, were determined. The amino terminal half of the S glycoprotein
      gene including antigenic sites A, B, C and D, were amplified by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Amplified PCR products were
      cloned, sequenced, and compared with published sequences for non-Korean TGEV
      strains. Korea TGEV field strains had 98.5-99.5% nucleotide sequence and 97.2
      99.0% amino acid sequence similarity with each other. They had 96.5-99.0%
      nucleotide sequence similarity and 94.9-97.6% amino acid sequence similarity
      compared to non-Korean TGEV strains. Korean TGEV strains had several specific
      nucleotide and amino acid sequences which were not found in foreign TGEV or PRCV
      strains. HKT2 strain differed by 0.89% in nucleotide and 2.03% amino acid
      sequences compared to original KT2 strain although the regions forming four
      antigenic sites were not changed. By phylogenetic tree analysis, Korean field
      TGEV strains were branched into different groups from non-Korean TGEV or PRCV
      strains. Korean TGEV field strains KT2 and 133 were branched in separate groups
      that were differentiated from the other Korean TGEV strains. The Korean TGEV
      strains seemed to be evolved from a separate lineage of TGEV strain.

PMID- 12814888
TI  - Susceptibility of Salmonella isolated from fish feed factories to disinfectants
      and air-drying at surfaces.
AB  - The objective of this work was to determine whether persistence of certain
      Salmonella isolates in fish feed factories involved enhanced resistance to
      disinfectants or air-drying. Salmonella isolates known to be persistent in fish
      feed factories and Salmonella isolates from other origins were tested for their
      sensitivity to nine disinfectants by using a suspension test. More than
      5log(10)reduction in viable count for all isolates was only achieved by two of
      the disinfectants at 80% of the lowest recommended user concentration. However,
      Salmonella isolates from fish feed factories were not more resistant to
      disinfectants compared to Salmonella from other origins. For four of the
      disinfectants, presence of fish feed had a more adverse effect on disinfection
      efficacy compared to the protein bovine serum albumin (BSA). In general, the
      Salmonella isolates were more resistant to disinfection than Escherichia coli DSM
      682, a strain recommended in testing of disinfectants. The Salmonella isolates
      were also tested for their ability to survive air-drying at stainless steel
      surfaces, but there were no differences in survival of isolates from fish feed
      factories compared to isolates of other origin. In conclusion the Salmonella
      isolates from fish feed factories were not particularly resistant to disinfection
      or air-drying at surfaces. The data show that disinfectants to be used against
      Salmonella should be thoroughly tested and selected, since not all disinfectants
      appear to be effective against Salmonella.

PMID- 12814889
TI  - Diagnosis of histoplasmosis by detection of the internal transcribed spacer
      region of fungal rRNA gene from a paraffin-embedded skin sample from a dog in
      Japan.
AB  - The lesions of histoplasmosis in dogs in Japan differ from those in dogs in North
      America. Affected dogs in Japan have had multiple granulomatous or ulcerated foci
      in skin or gingiva and have not had pulmonary or gastrointestinal lesions. The
      present report introduces a polymerase chain reaction (PCR) diagnosis of canine
      histoplasmosis and the characteristic of disease in Japan. The surgically removed
      skin ulcerate samples from a 5-years-old female Shiba-inu native to Japan without
      traveling out of the country were evaluated. Tissue samples had many yeast-like
      organisms in the macrophages. DNA was extracted from paraffin-embedded tissue
      samples. A nested PCR technique was applied. The detected sequence of the
      internal transcribed spacer of ribosomal RNA gene had 99.7% in homology with
      Ajellomyces capsulatus (the teleomorph of Histoplasma capsulatum). Clinical
      manifestations, historical background of equine epizootic lymphangitis in Japan,
      and a human autochthonous case of histoplasmosis farciminosi indicated that this
      dog might have been infected with H. capsulatum var. farciminosum as a
      heteroecism.

PMID- 12814890
TI  - Molecular typing of isolates of Clostridium perfringens from healthy and diseased
      poultry.
AB  - The bacterium Clostridium perfringens can cause both clinical and subclinical
      disease in poultry. To study the pathogenesis and epidemiology of disease caused
      by C. perfringens, methods for typing its various strains need to be evaluated.
      C. perfringens isolates from healthy and diseased poultry from different parts of
      Sweden were analysed by polymerase chain reaction (PCR) in order to establish the
      presence of alpha-, beta-, beta2-, epsilon -, iota- and enterotoxin genes. In
      order to subtype C. perfringens isolates, the two methods amplified fragment
      length polymorphism (AFLP) and pulsed field gel electrophoresis (PFGE) were
      compared on 21 C. perfringens isolates from 10 different farms. In a second
      study, 32 isolates of C. perfringens type A from three broilers from a healthy
      flock reared without ionophorous anticoccidials were subtyped by PFGE. All 53
      isolates analysed with PCR belonged to the toxin type A of C. perfringens, with
      the gene coding for alpha-toxin production. Two isolates possessed the beta2-gene
      as well, but none had the other toxin genes. Both AFLP and PFGE differentiated 21
      strains into 10 different subtypes. This differentiation correlated closely with
      the origins of the isolates. Unique subtypes were isolated from seven farms. Only
      isolates from birds of one farm demonstrated more than one subtype of C.
      perfringens. The subtyping of the isolates from a healthy flock showed that each
      bird carried two to three different subtypes and two different subtypes were
      found in the same kind of tissue sample in four cases. Three of the four
      different subtypes found in this study were new, compared with the first study.
      AFLP and PFGE were found to be equally suitable for subtyping of C. perfringens
      isolates. The wide variation in subtypes in the healthy broilers could be the
      result of the antibiotic-free rearing of these birds.

PMID- 12814891
TI  - Comparison of Pseudomonas aeruginosa isolates from mink by serotyping and pulsed
      field gel electrophoresis.
AB  - Isolates of Pseudomonas aeruginosa from clinical infections in mink were
      subjected to serotyping and pulsed-field gel electrophoresis (PFGE) using SpeI. A
      total of 212 isolates of P. aeruginosa from the year 1998 to 2001 were included
      in this study: 168 isolates from mink obtained from 74 farm outbreaks of
      haemorrhagic pneumonia. Isolates from mink were separated into 34 distinct clones
      by PFGE subtyping. All isolates from mink infected during the same farm outbreak
      were identical, except in one case where two different strains were isolated from
      mink obtained from the same farm outbreak. P. aeruginosa of specific PFGE types
      were found to cause clusters of outbreaks on several farms within a few weeks of
      each other. However, PFGE types of strains causing clusters of farm outbreaks
      changed from year to year. These results suggest that some outbreaks of
      haemorrhagic pneumonia are caused by pathogenic strains of P. aeruginosa spread
      between farms and animals either mechanically, or through feed or water from a
      common source, rather than by random nosocomial infections with strains from the
      farm environment.

PMID- 12814892
TI  - Competitive exclusion by Bacillus subtilis spores of Salmonella enterica serotype
      Enteritidis and Clostridium perfringens in young chickens.
AB  - Cost effective control of avian diseases and food borne pathogens remains a high
      priority for all sectors of the poultry industry with cleansing and disinfection,
      vaccination and competitive exclusion approaches being used widely. Previous
      studies showed that Bacillus subtilis PY79(hr) was an effective competitive
      exclusion agent for use in poultry to control avian pathogenic Escherichia coli
      serotype O78:K80. Here we report experiments that were undertaken to test the
      efficacy of B. subtilis PY79(hr) in the control of Salmonella enterica serotype
      Enteritidis and Clostridium perfringens in young chickens. To do this, 1-day-old
      and 20-day-old specific pathogen free (SPF) chicks were dosed with a suspension
      of B. subtilis spores prior to challenge with S. Enteritidis (S1400) and C.
      perfringens, respectively. For both challenge models, a single oral inoculum of
      1x10(9) spores given 24h prior to challenge was sufficient to suppress
      colonisation and persistence of both S. Enteritidis and C. perfringens. In
      particular, the faecal shedding of S. Enteritidis, as measured by a semi
      quantitative cloacal swabbing technique, was reduced significantly for the 36
      days duration of the experiment. B. subtilis persisted in the intestine although
      with decreasing numbers over the same period. These data add further evidence
      that B. subtilis spores may be effective agents in the control of avian diseases
      and food borne pathogens.

PMID- 12814893
TI  - Analysis by pulsed-field gel electrophoresis of the genetic diversity among
      Clostridium perfringens isolates from chickens.
AB  - The aim of this study was to analyse the genetic diversity among Clostridium
      perfringens isolates from Danish broiler chickens since both sick and presumably
      healthy animals were investigated. Isolates (n=279) collected from chickens from
      25 farms were analysed by pulsed-field gel electrophoresis (PFGE) with the
      restriction enzyme SmaI. A high genetic diversity was found. Isolates with
      different PFGE types were toxin typed by PCR and all were found to be of type A.
      The results showed that healthy broiler chickens carried several different C.
      perfringens clones both within a flock and even within individual birds, whereas
      flocks suffering from necrotic enteritis (NE) or cholangio-hepatitis carried only
      one or two clones.

PMID- 12814894
TI  - The effects of prenatal alcohol exposure on infant mental development: a meta
      analytical review.
AB  - AIMS: Although research on fetal alcohol exposure has had a significant effect on
      social norms and public policy, there has been little quantitative review of this
      literature. METHODS: Meta-analysis was used to examine the effects of prenatal
      alcohol exposure on infant mental development, assessed using the Mental
      Development Index (MDI) from the Bayley Scales of Infant Development, a widely
      used, standardized measure. The current study examined the effects of three
      levels of average daily exposure during pregnancy: less than 1 drink per day, 1
      1.99 drinks per day and 2 or more drinks per day. Analyses were conducted
      separately for effects derived from observations of 6-8-, 12-13- and 18-26-month
      old children. RESULTS: Fetal alcohol exposure at all three dosage levels was
      associated with significantly lower MDI scores among 12-13-month-olds. The effect
      was attenuated, but not eliminated, when effect sizes adjusted for relevant
      covariates were used. For younger and older children, the effect of fetal alcohol
      exposure did not attain statistical significance at any dosage level.
      CONCLUSIONS: This pattern of results may reflect differences in MDI item content
      at different ages and the differential sensitivity of these abilities to prenatal
      alcohol exposure. Because the body of relevant literature is neither large nor
      conclusive, and because of heterogeneity in measurement, analysis and samples,
      caution is urged in interpreting results. Future research would benefit from use
      of more specific measures of infant outcomes and consideration of the impact of
      relevant covariates, different dosage patterns and timing of drinking on infant
      mental development.

PMID- 12814895
TI  - Relationship between dopamine D2 receptor-associated responses and operant
      ethanol self-administration in the rat: a factor analysis.
AB  - AIMS: To characterize the relationship between dopamine D(2) receptor-associated
      responses and operant ethanol self-administration in Wistar rats. METHODS: Thirty
      two rats were first tested for apomorphine-induced sniffing and raclopride
      induced catalepsy. Subsequently, the same subjects were initiated to lever press
      for ethanol in the sucrose-fading procedure. The subjects were allowed to respond
      for 8% v/v ethanol for 20 days. A factor analysis was used to characterize the
      relationship between D(2)-associated responses and parameters of sucrose and
      ethanol self-administration. RESULTS: The analysis revealed three factors
      accounting for 88.3% of the total variability. The first factor comprised only
      parameters of ethanol-reinforced behaviour. Parameters of sucrose self
      administration and cataleptic responses to raclopride loaded heavily on the
      second and third factors, respectively. None of the factors comprised apomorphine
      induced stereotypy. CONCLUSIONS: It appears that there is no relationship between
      apomorphine-induced sniffing, raclopride-induced catalepsy and operant responding
      for ethanol in Wistar rats. Our results, combined with previous reports, suggest
      that D(2) receptors are not primarily involved in the regulation of ethanol
      reinforcement.

PMID- 12814896
TI  - Lack of ifenprodil anxiolytic activity after its multiple treatment in
      chronically ethanol-treated rats.
AB  - AIMS: The purpose of this study was to assess the anxiolytic activity of
      ifenprodil in Warsaw high-preferring (WHP) and low-preferring (WLP) rats after
      chronic ethanol treatment. METHODS: WHP and WLP animals, their paired-ethanol
      naive groups and control Wistar rats were treated with ifenprodil (1.0 mg/kg,
      intraperitoneally) for 21 consecutive days. Anxiolytic activity was evaluated by
      using the two-compartment exploratory test. In addition, the locomotor activity
      paradigm was also assessed. RESULTS: Ifenprodil did not affect this paradigm in
      all investigated groups. The ethanol treatment led to lowering of anxiolytic
      scores in WHP rats. Multiple ifenprodil administration showed an anxiogenic-like
      activity in both WHP- and WLP-ethanol-treated groups. CONCLUSIONS: Our results
      suggest that, under some conditions, the role of ifenprodil in the treatment of
      alcoholism may be insufficient to support its use.

PMID- 12814897
TI  - The effects of chronic ethanol consumption and ethanol withdrawal on serum
      cholinesterase activity in rats.
AB  - AIMS: The effect of chronic ethanol consumption and ethanol withdrawal on serum
      cholinesterase (ChE) activity was investigated in female Wistar rats. METHODS:
      Ethanol was administered by a modified liquid diet with 4.8% (v/v) ethanol for 3
      days followed by 25 days on a liquid diet in which the ethanol concentration was
      increased to 7.2%. Control rats were pair-fed with an isocaloric liquid diet not
      containing ethanol. The blood ethanol concentration and serum ChE activity were
      measured at the end of the 4.8% ethanol consumption period; after 7, 14 and 35
      days of ethanol (7.2%) consumption, and at 24 and 72 h after ethanol withdrawal
      following ethanol consumption of 35 days. RESULTS: Daily ethanol consumption of
      the rats ranged from 11.5 to 14.9 g/kg. Serum ChE activity was found
      significantly increased from the 3rd day of ethanol (4.8%) consumption. Serum ChE
      activities of the rats receiving 7.2% ethanol also increased significantly
      compared with rats ingesting 4.8% ethanol. Blood ethanol levels were measured as
      121 and 0.88 mg/dl on the 35th day of ethanol (7.2%) consumption (just before
      ethanol withdrawal) and after 24 h of ethanol withdrawal, respectively. Increased
      serum ChE activity (1968 U/l) was still observed (1942 U/l) after 24 h of ethanol
      withdrawal. ChE activity returned to control levels (501 U/l) after 72 h of
      ethanol withdrawal. Audiogenic seizures indicating development of physical
      dependence on ethanol were also observed after 8 h of ethanol withdrawal in
      another individual group of ethanol-fed rats. CONCLUSIONS: Our results show that
      serum ChE activity is increased by chronic ethanol consumption in rats and that
      this increase is affected by ethanol concentration and duration of ethanol
      ingestion.

PMID- 12814898
TI  - Subnormal alpha-2-adrenoceptor-mediated sedation during 6 months of sobriety in
      male type 1 alcohol-dependent subjects.
AB  - AIMS: In the present study, alpha(2)-adrenoceptor function was investigated over
      6 months of sobriety in eight male alcohol-dependent subjects. METHODS: Subjects
      were investigated with repeated clonidine (CLON, 2 micro g/kg body weight
      intravenously) challenge tests at days 1 and 7, and months 2 and 6 after the end
      of a period of heavy alcohol intake. CLON-induced sedation was rated at challenge
      tests. Mental well-being was self-reported before all challenge tests. Three
      challenge tests were performed at 1-week intervals in six male healthy controls.
      RESULTS: Sedation was significantly lower after CLON at all time-points for the
      challenge tests in alcohol-dependent subjects compared with mean values for three
      challenge tests in controls. Three dimensions of mental well-being were
      negatively correlated with scores of CLON-induced sedation at month 6.
      CONCLUSIONS: alpha(2)-Adrenoceptor function is subnormal, as assessed by CLON
      induced sedation, for at least 6 months after termination of alcohol intake.
      Whether this subnormal receptor function is pre-existing and possibly genetically
      determined or is a consequence of long-term alcohol intake must be further
      investigated, as should this receptor status in alcohol-dependent subjects with
      longer time-periods of sobriety.

PMID- 12814899
TI  - Alcohol consumption among middle-aged and elderly men: a community study from
      western India.
AB  - AIMS: To assess the prevalence and pattern of alcohol use in a middle-aged and
      elderly population in Mumbai, India. METHODS: 50 220 men aged >/=45 years from
      the lower and lower-middle section of the general population were interviewed.
      RESULTS: 18.8% were currently consuming alcoholic beverages, of whom 32.8% drank
      on at least 6 days per week. The most popular beverage was locally distilled
      products of fruits and grain (country liquor). Seventy-five per cent of the
      consumers of country liquor would consume over 53 g of ethanol on a day when they
      drank, with 46.6% of these doing so on at least 6 days per week. CONCLUSIONS:
      Abstinence, and also heavy and frequent use of alcohol, are common in this
      population and the latter is likely to have significant public health
      implications.

PMID- 12814900
TI  - Event-related potential responses to alcohol-related stimuli in African-American
      young adults: relation to family history of alcoholism and drug usage.
AB  - AIMS: To use event-related potentials (ERPs) to investigate the response to
      alcohol-related stimuli in African-American young adults. METHODS: ERPs to an
      object recognition task, that included pictures of objects, food and alcohol
      related and non-alcohol-related drinks as stimuli, were obtained in 81 African
      American young adult men and women (18-25 years old) without a personal history
      of alcohol dependence. Information on: psychiatric diagnoses, personal drinking
      and drug use history, and familial history of alcoholism was also obtained.
      RESULTS: Family history was found to be associated with lowered P3 components and
      higher N1 components in response to the non-alcohol-related drinks. Additionally,
      an exploratory analyses revealed that lower amplitude N1 components were
      generated in response to alcohol-related stimuli in regular marijuana users
      compared with non-regular users. No associations of N1 or P3 amplitudes with
      conduct disorder symptoms or current drinking status were found in this
      population. CONCLUSIONS: These studies demonstrated that family history is
      significantly and selectively associated with lower P3 amplitudes in this group
      of young adult men and women of African-American heritage. Additionally, current
      usage of marijuana and alcohol do not modify P3 amplitudes. However, regular
      marijuana use may diminish N1 response to alcohol-related stimuli, whereas,
      family history of alcoholism may augment N1 responses. Taken together these
      studies further suggest that ERPs can provide specific information on alcoholism
      risk as well as use of other misused drugs.

PMID- 12814901
TI  - Estimation of tobacco- or alcohol-attributable disease rates in national hospital
      care: an approach based on routine in-patient disease register data and
      systematic diagnosis of alcohol use disorders.
AB  - AIMS: The goal of this paper was to estimate and compare the numbers and rates of
      tobacco- or alcohol-attributable disease (TAAD) in in-patient-treated cases in a
      high tobacco smoking and alcohol consumption country, based on different
      estimates. METHODS: Two samples, three TAAD estimates, and tobacco- or alcohol
      attributable fractions were used. Sample 1 included all disease cases aged 25-64
      years and treated more than 24 h as in-patients during the year 1997 (n = 7 344
      079) in the hospitals in Germany. Sample 2 included all in-patients aged 25-64
      years (n = 1136) consecutively admitted to one general hospital. The first
      estimate of the TAAD was the routine main diagnosis based on the treating
      physician's report to the in-patient disease register (IDR) in sample 1. The
      second estimate included up to three routine treatment diagnoses in sample 2, and
      the third estimate a diagnosis of alcohol dependence or misuse according to DSM
      III-R or ICD-10, as well as harmful or hazardous alcohol consumption, in sample
      2. The tobacco- and alcohol-attributable fractions were calculated based on the
      method for the estimation of tobacco- and alcohol-attributable mortality,
      originally provided for the Centers for Disease Control in the USA. RESULTS: When
      the three estimates were combined, a total of 37.8% of all in-patient treatment
      cases had at least one diagnosis that was attributable in part or fully to
      tobacco smoking, alcohol dependence, alcohol misuse, or harmful or hazardous
      alcohol drinking. When the tobacco- and the alcohol-attributable fractions were
      considered, of all treatment cases, 10.5% could be revealed as attributable to
      smoking or alcohol consumption according to the one main diagnosis based on the
      IDR. When all three estimates were combined, the rate was 30.2%. This
      corresponded to 32.2% of the national in-patient hospital care costs.
      CONCLUSIONS: The TAAD rate is underestimated when using one routine diagnosis
      alone. Additional alcohol misuse or dependence diagnoses are needed, which may be
      obtained with a reasonable level of resources in a sample of hospitals. TAAD
      rates may be used for the planning and practice of brief intervention and as an
      outcome measure for population-based intervention.

PMID- 12814902
TI  - Urinary ethyl glucuronide and 5-hydroxytryptophol levels during repeated ethanol
      ingestion in healthy human subjects.
AB  - AIMS: This study investigated the stability and reproducibility of urinary ethyl
      glucuronide (EtG) and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindole-3
      acetic acid (5-HIAA) ratio, both of which are used as biochemical markers of
      recent alcohol consumption, after single and multiple oral doses of ethanol in
      healthy human subjects. METHODS: Nine females aged 19-27 years drank ethanol (8%,
      w/v, in juice) or placebo (juice) in random order. The intervention consisted of
      0.4 g/kg (22-28 g) of ethanol or placebo twice daily (in the morning and evening)
      during 8 consecutive days, starting in the evening on day 1. Spot urine samples
      of the first morning void were collected during the 8-day drinking period and for
      another 3 days (days 9-11) with no intake of ethanol or placebo. Ethanol, EtG, 5
      HTOL and 5-HIAA were determined in the urine samples by headspace GC, LC-MS, GC
      MS and HPLC, respectively. RESULTS: The individual results during the drinking
      period were highly variable, both within and between subjects, ranging from 0-7.3
      mmol/l for ethanol, 1.4-71.0 mg/l for EtG, 0.1-4.5 mg/mmol for the EtG/creatinine
      ratio, and 2-109 nmol/ micro mol for 5-HTOL/5-HIAA. The placebo group
      consistently showed negative values for ethanol (< 0.1 mmol/l) and 5-HTOL/5-HIAA
      (< 15 nmol/ micro mol), but two samples were positive for EtG (> 0.1 mg/l). In
      the morning of day 9 (i.e. approximately 14-15 h after the last dose), ethanol
      was no longer measurable in urine and the 5-HTOL/5-HIAA ratio had returned to
      below the reference value, but detectable levels of EtG (11.3 +/- 6.0 mg/l, mean
      +/- SD) and the EtG/creatinine ratio (1.0 +/- 0.3 mg/mmol) were found in all
      samples. CONCLUSIONS: The results confirm the increase in urinary EtG and 5-HTOL
      levels during acute ethanol intake, although the individual values were highly
      variable both within and between subjects. No significant accumulation of either
      compound occurred upon multiple-dose administration of 0.8 g/kg (44-57 g) ethanol
      per day for approximately 1 week.

PMID- 12814903
TI  - Childhood attention deficit/hyperactivity disorder and alcohol dependence: a 1
      year follow-up.
AB  - AIMS: To investigate the onset and outcome of alcohol dependence in subjects with
      childhood attention deficit/hyperactivity disorder (ADHD) in a Turkish sample.
      METHODS: Among patients being treated for alcohol dependence, 15 had a history of
      childhood ADHD [ADHD (+)] and 45 did not [ADHD (-)]. ADHD history was assessed
      according to DSM-IV criteria by a child and adolescent psychiatrist who
      interviewed the subjects and their close relatives. Severity of dependence was
      measured by the Michigan Alcoholism Screening Test. Subjects were followed up for
      1 year for the assessment of relapse. RESULTS: The age of onset for alcohol
      drinking, alcohol abuse and alcohol dependence were significantly lower in the
      ADHD (+) group than in the ADHD (-) group. Comorbid substance use was more
      prevalent in the ADHD (+) group. The study found no significant difference in the
      severity of alcohol dependence between ADHD (+) and ADHD (-) groups. During
      follow-up, 80% of the ADHD (+) subjects relapsed, compared with 55.6% in the ADHD
      (-) group. Relapse occurred on average 2.74 months earlier in the ADHD (+) group
      than in the ADHD (-) group. CONCLUSIONS: As found in other countries, alcohol
      dependence in Turkish subjects with childhood ADHD starts early and is relatively
      resistant to treatment. Early diagnosis and treatment of ADHD might help prevent
      alcohol- and substance-related disorders.

PMID- 12814904
TI  - Case report: managing fractures in non-compliant alcoholic patients--a
      challenging task.
AB  - AIMS: To investigate whether there are extractable conclusions for limb fracture
      management in dependent alcoholics. METHODS: We discuss four cases of dependent
      alcoholics who presented in our department over a 12-month period, and who
      developed significant complications owing to non-compliance with treatment.
      RESULTS: Initial treatment, although appropriate, failed because of non
      compliance. This led to further admissions, wound infections and surgery to
      enable cure. CONCLUSIONS: Our case reports indicate that for upper limb fractures
      of the middle third of the humerus, non-operative treatment or internal fixation
      with out-patient detoxification is appropriate. Lower limb fractures, on the
      other hand, should be dealt with by external fixation and in-patient
      detoxification. It is imperative that the alcohol dependence is addressed if we
      are to decrease non-compliance.

PMID- 12814905
TI  - The role of anxiety in predicting drinking behaviour.
AB  - AIMS: We investigated whether reduced anxiety predicted improved drinking
      outcomes over and above age of onset and ondansetron treatment among alcoholics
      enrolled in a clinical trial. METHODS: Study design was a 2 (early onset
      alcoholics versus late onset alcoholics) x 4 (placebo and ondansetron 1, 4 and 16
      micro g/kg twice daily) factorial randomized clinical trial during which all
      participants received weekly group cognitive behavioural therapy. Using weighted
      least squares regression, we examined the effects of ondansetron dose, age of
      onset, pre-treatment drinking and anxiety level (measured by Profile of Mood
      States) on end-state drinking behaviour. Our previous studies have demonstrated
      that ondansetron dose, age of onset and pre-treatment drinking influence end
      state drinking behaviour. RESULTS: and conclusions: The present study added to
      our previous knowledge, indicating that when change in anxiety level was included
      as a predictor of end-state drinking, it also accounted for a significant
      proportion of the variance. Those who experienced decreases in anxiety during the
      treatment reported fewer drinks per day at their last visit compared with those
      who reported increases in anxiety.

PMID- 12814906
TI  - Leptin levels of alcohol abstainers and detoxification patients are not
      different.
AB  - AIMS: Leptin is a cytokine-type peptide hormone, recently implicated as a
      putative state marker of alcohol use and in craving. Our goal was to evaluate the
      potential of leptin as a state and trait marker and to rule out the role of
      current alcohol intoxication on leptin levels. METHODS: Eighteen alcohol
      withdrawal patients (16 males, 2 females) whose blood contained 202 mg/dl
      (median) of ethanol at hospitalization, who had a median age of 43.5 years and
      had consumed 1075 g of ethanol (median) in the last 7 days were included in the
      study. Leptin was determined in samples at day 1 (when still intoxicated) and day
      7 of withdrawal. Expected leptin levels were calculated with a formula. For
      comparison, 27 blood samples of 18 abstinent persons, matched for gender, age and
      body mass index were used. Furthermore, mean cell volume, gamma-glutamyl
      transferase (GGT), blood glucose, cholesterol, triglycerides and body composition
      (bioimpedance device) were determined. For statistical analysis, SPSS 11 was
      used. RESULTS: Expected leptin levels were 1.71 ng/ml (median), leptin measured
      at day 1 was 2.65 ng/ml (median) and 2.85 ng/ml on day 7 for the alcohol
      withdrawal patients and 2.2 ng/ml (median) for the abstainers. These
      concentrations were not significantly different. Significant correlations were
      found between leptin day 1 and expected leptin levels, percentage fat body mass,
      cigarettes smoked per day, GGT and blood alcohol concentration. CONCLUSIONS: Our
      preliminary data do not support the hypothesis of leptin as a state or trait
      marker and suggest only a minor influence of acute intoxication on leptin levels
      in alcohol detoxification patients.

PMID- 12814907
TI  - Acupuncture for alcohol withdrawal: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Previous trials on acupuncture in alcohol addiction were in
      outpatients and focused on relapse prevention. Rates of dropout were high and
      interpretation of results difficult. We compared auricular laser and needle
      acupuncture with sham laser stimulation in reducing the duration of alcohol
      withdrawal. METHODS: Inpatients undergoing alcohol withdrawal were randomly
      allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham
      laser stimulation (n = 16). Attempts were made to blind patients, therapists and
      outcome assessors, but this was not feasible for needle acupuncture. The duration
      of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary
      outcome; the duration of sedative prescription was the secondary outcome.
      RESULTS: Patients randomized to laser and sham laser had identical withdrawal
      symptom durations (median 4 days). Patients randomized to needle stimulation had
      a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham
      intervention), and tended to have a shorter duration of sedative use, but these
      differences diminished after adjustment for baseline differences. CONCLUSIONS:
      The data from this pilot trial do not suggest a relevant benefit of auricular
      laser acupuncture for alcohol withdrawal. A larger trial including adequate sham
      interventions is needed, however, to reliably determine the effectiveness of any
      type of auricular acupuncture in this condition.

PMID- 12814908
TI  - Detecting thiamine in beer.
AB  - AIMS: To ascertain whether thiamine HCl could be detected in beer using a double
      blind triangular taste test. METHODS: Three 100 ml samples of beer to which 10 or
      0 mg of thiamine were added were presented in counterbalanced order to 49
      volunteers. Subjects consumed and rated each sample separately for taste and
      appearance and chose which beer was different. RESULTS: Thiamine-enriched beer
      could not be reliably distinguished from normal beer. However, a significant
      perceptual taste difference was found, with participants rating thiamine
      fortified beer as more bitter than normal beer. CONCLUSIONS: Thiamine was found
      to alter the perception of bitterness of beer, but thiamine-fortified beer could
      not be reliably distinguished from normal beer.

PMID- 12814909
TI  - The effects of carbon dioxide in champagne on psychometric performance and blood
      alcohol concentration.
AB  - AIMS: To assess the effects of carbon dioxide (CO(2)) in champagne on psychomotor
      performance and blood-alcohol concentration (BAC). METHODS: Twelve subjects
      consumed ethanol (0.6 g/kg body weight) served as champagne or champagne with the
      CO(2) removed, in a crossover study. RESULTS: Champagne produced significantly
      greater BACs and significantly increased reaction times in a divided attention
      task, than degassed champagne. CONCLUSIONS: The CO(2) in champagne may accelerate
      absorption of alcohol, leading to more rapid or severe intoxication.

PMID- 12814910
TI  - Alcohol intake after serotonin transporter inactivation in mice.
AB  - Knock-out mice lacking the serotonin transporter [5-hydroxytryptamine transporter
      (5-HTT)] were used to assess the influence of 5-HT re-uptake on ethanol
      consumption. Under a free-choice paradigm, alcohol intake was lower in mutant
      than in wild-type mice, and pharmacological blockade of 5-HTT by fluoxetine
      reduced alcohol intake in wild-type mice only. These data confirm the inhibitory
      effect of 5-HTT inactivation on ethanol intake.

PMID- 12814911
TI  - Effect of indomethacin on force responses and sarcoplasmic reticulum function in
      skinned skeletal muscle fibers and cytosolic [Ca2+] in myotubes.
AB  - In this study, the effects of phospholipase A2 (PLA2) inhibitors on excitation
      contraction coupling (ECC) and sarcoplasmic reticulum (SR) function were examined
      in skinned extensor digitorum longus (EDL) muscle fibers of the rat. The
      nonspecific PLA2 inhibitor indomethacin (200 microM) significantly increased the
      peak (approximately 2-fold, P = 0.02) and the width (approximately 6-fold, P =
      0.008) of depolarization-induced force responses (DIFRs) elicited in the fibers
      (n = 4). Exposure of the skinned EDL fibers to indomethacin (200 microM) (n = 7)
      and another PLA2 inhibitor quinacrine (200 microM) (n = 5) resulted in the return
      of large DIFRs after use-dependent rundown. However, aristolochic acid (100
      microM), an inhibitor of secretory PLA2, failed to return DIFRs after rundown.
      Indomethacin did not protect against the loss of DIFRs induced by exposure to
      elevated myofibrillar [Ca2+]. Indomethacin (200 microM) produced a small but
      significant increase in the Ca2+ sensitivity of the contractile apparatus of
      skinned EDL fibers and the maximum force production. Indomethacin (200 microM)
      also had significant effects on SR function, increasing SR Ca2+ loading in the
      skinned fibers (117.2 +/- 3.0% of controls, P = 0.0008, n = 8) and inducing
      intracellular Ca2+ release in isolated intact flexor digitorum brevis (FDB)
      fibers (n = 7) and C2C12 myotubes (n = 6). These data suggest that intracellular
      PLA2 may be an important modulator of ECC in skeletal muscle.

PMID- 12814912
TI  - Channels formed with a mutant prion protein PrP(82-146) homologous to a 7-kDa
      fragment in diseased brain of GSS patients.
AB  - A major prion protein (PrP) mutant that forms amyloid fibrils in the diseased
      brain of patients with Gerstmann-Straussler-Scheinker syndrome (GSS) is a
      fragment of 7 kDa spanning from residues 81-82 to 144-153 of PrP. Analysis of
      ionic membrane currents, recorded with a lipid bilayer technique, revealed that
      the wild-type fragment PrP(82-146) WT and the partially scrambled PrP(82-146)
      (127-146) SC are capable of forming heterogeneous ion channels that are similar
      to those channels formed with PrP(106-126). In contrast, PrP(82-146) peptides in
      which the region from residue 106 to 126 had been scrambled (SC) showed a
      reduction in interaction with lipid membranes and did not form channels. The
      PrP(82-146) WT- and PrP(82-146) (127-146) SC-formed cation channels with fast
      kinetics are Cu2+ sensitive and rifampicin (RIF) insensitive, whereas the time
      dependent inactivating channels formed by these same peptides are both Cu2+ and
      RIF insensitive. The presence of RIF in the solution before the addition of
      PrP(82-146) WT or PrP(82-146) (127-146) SC affected their incorporation into the
      lipid bilayers. PrP(82-146) WT and PrP(82-146) (127-146) SC fast cation channels
      formed in the presence of RIF appeared in an electrically semisilent state or an
      inactivated state. Increasing [Cd2+]cis enhanced the incorporation of PrP(82-146)
      WT and PrP(82-146) (127-146) SC channels formed in the presence of RIF. We
      conclude that the major PrP mutant fragment in the diseased brain of GSS patients
      is prone to form channels in neuronal membranes, causing their dysfunction. We
      propose that Cd2+ may accentuate the neurotoxicity of this channel-forming PrP
      fragment by enhancing its incorporation into the membrane.

PMID- 12814913
TI  - Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance
      induction through abbreviated neurotoxic signaling.
AB  - Transient exposure of rat cortical cultures to nonlethal oxygen-glucose
      deprivation (OGD preconditioning) induces tolerance to otherwise lethal oxygen
      glucose deprivation (OGD) or N-methyl-D-aspartate 24 h later. This study
      evaluates the role of cytosolic and mitochondrial Ca2+-dependent cellular
      signaling. Mechanistic findings are placed in context with other models of
      ischemic preconditioning or known neurotoxic pathways within cortical neurons.
      Tolerance to otherwise lethal OGD is suppressed by performing OGD preconditioning
      in the presence of the broad-scope catalytic antioxidants Mn(III)tetra(4
      carboxyphenyl)porphyrin (MnTBAP) or Zn(II)tetra(4-carboxyphenyl)porphyrin
      [Zn(II)TBAP], but not by a less active analog, Mn(III)tetra(4
      sulfonatophenyl)porphyrin, or a potent superoxide scavenger, Mn(III)tetra(N-ethyl
      2-pyridyl)porphyrin chloride. Inhibitors of adenosine A1 receptors, nitric oxide
      synthase, mitogen-activated protein kinase, and poly(ADP-ribose) polymerase fail
      to suppress OGD preconditioning despite possible links with reactive oxygen
      species in other models of ischemic preconditioning. Preconditioning is
      suppressed by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which has
      been ascribed elsewhere to inhibition of superoxide transport to the cytosol
      through mitochondrial anion channels. However, although it induces mitochondrial
      Ca2+ uptake, neuronal preconditioning is largely insensitive to mitochondrial
      uncoupling with carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone or 2,4
      dinitrophenol. Un-couplers will prevent production of mitochondrial reactive
      oxygen species, implying nonmitochondrial targets by MnTBAP, Zn(II)TBAP, and
      DIDS. Emphasizing the importance of an increase in cytosolic Ca2+ during
      preconditioning, a Ca2+/calmodulin-dependent protein kinase II inhibitor, KN-62,
      suppresses development of subsequent tolerance. Summarizing, only those cellular
      transduction pathways that have the potential to be neurotoxic may be activated
      by preconditioning in cortical neurons. Finally, a marked decrease in
      extracellular glutamate is observed during otherwise lethal OGD in preconditioned
      cultures, suggesting that this end effector may represent a point of convergence
      across different preconditioning models.

PMID- 12814914
TI  - Cu2+-induced modification of the kinetics of A beta(1-42) channels.
AB  - We found that the amyloid beta peptide A beta(1-42) is capable of interacting
      with membrane and forming heterogeneous ion channels in the absence of any added
      Cu2+ or biological redox agents that have been reported to mediate A beta(1-42)
      toxicity. The A beta(1-42)-formed cation channel was inhibited by Cu2+ in cis
      solution ([Cu2+]cis) in a voltage- and concentration-dependent manner between 0
      and 250 microM. The [Cu2+]cis-induced channel inhibition is fully reversible at
      low concentrations between 50 and 100 microM [Cu2+]cis and partially reversible
      at 250 microM [Cu2+]cis. The inhibitory effects of [Cu2+]cis between 50 and 250
      microM on the channel could not be reversed with addition of Cu2+-chelating agent
      clioquinol (CQ) at concentrations between 64 and 384 microM applied to the cis
      chamber. The effects of 200-250 microM [Cu2+]cis on the burst and intraburst
      kinetic parameters were not fully reversible with either wash or 128 microM
      [CQ]cis. The kinetic analysis of the data indicate that Cu2+-induced inhibition
      was mediated via both desensitization and an open channel block mechanism and
      that Cu2+ binds to the histidine residues located at the mouth of the channel. It
      is proposed that the Cu2+-binding site of the A beta(1-42)-formed channels is
      modulated with Cu2+ in a similar way to those of channels formed with the prion
      protein fragment PrP(106-126), suggesting a possible common mechanism for Cu2+
      modulation of A beta and PrP channel proteins linked to neurodegenerative
      diseases.

PMID- 12814915
TI  - Differential relaxing responses to particulate or soluble guanylyl cyclase
      activation on endothelial cells: a mechanism dependent on PKG-I alpha activation
      by NO/cGMP.
AB  - cGMP is generated in endothelial cells after stimulation of soluble guanylyl
      cyclase (sGC) by nitric oxide (NO) or of particulate guanylyl cyclase (pGC) by
      natriuretic peptides (NP). We examined whether localized increases in cytosolic
      cGMP have distinct regulatory roles on the contraction induced by H2O2 treatment
      in human umbilical vein endothelial cells. cGMP concentrations and temporal
      dynamics were different upon NO stimulation of sGC or C-type NP (CNP) activation
      of pGC and did not correlate with their relaxing effects measured as planar cell
      surface area after H2O2 challenge. cGMP production due to sGC stimulation was
      always smaller and more brief than that induced by pGC stimulation with CNP,
      which was greater and remained elevated longer. The NO effects on cell relaxation
      were cGMP dependent because they were blocked by sGC inhibition with 1H
      (1,2,4)Oxadiazolo(4,3-a)quinoxaline-1-one and mimicked by 8-Br-cGMP. An
      antagonist of the cGMP-dependent protein kinase type-I (PKG-I) also inhibited the
      NO-induced effects. The cell contraction induced by H2O2 produces myosin light
      chain (MLC) phosphorylation and NO prevented it completely, whereas CNP only
      produced a partial inhibition. Transfection with a dominant negative form of PKG
      type-I alpha completely reversed the NO-induced effects on MLC phosphorylation,
      whereas it only partially inhibited the effects due to CNP. Taken together, these
      results demonstrate that the NO/sGC/cGMP pathway induces endothelial cell
      relaxation in a more efficient manner than does CNP/pGC/cGMP pathway, an effect
      that might be related to a selective stimulation of PKG-1 alpha by NO-derived
      cGMP. Consequently, stimulated PKG-I alpha may phosphorylate important protein
      targets that are necessary to inhibit the endothelial contractile machinery
      activated by oxidative stress.

PMID- 12814916
TI  - Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia.

PMID- 12814917
TI  - No clinical evidence for CD4+ cell depletion caused by rituximab.

PMID- 12814918
TI  - Allogenic bone marrow transplantation: not a treatment yet for familial
      Mediterranean fever.

PMID- 12814920
TI  - The UK national patient dose database: now and in the future.

PMID- 12814919
TI  - S-nitrosohemoglobin is distinguished from other nitrosovasodilators by unique
      oxygen-dependent responses that support an allosteric mechanism of action.

PMID- 12814921
TI  - Radiosensitivity of the developing haemopoietic system in mammals and its adult
      consequences: animal studies.
AB  - The haemopoietic system in the developing mammal is very sensitive to the
      damaging effects of ionizing radiation. Epidemiological studies have established
      a strong association between obstetric exposure to diagnostic radiation and an
      increase in the incidence of childhood leukaemia and between low dose gamma
      irradiation during the early fetal period and mental retardation in children. It
      has been suggested that insufficient oxygen supply to the developing brain due to
      radiation induced damage to fetal haemopoietic tissue has a role in inducing the
      severe mental retardation observed in the Japanese children exposed to atom bomb
      radiation in utero. Experimental studies have shown that X- and gamma irradiation
      of pregnant mice with <1 Gy during the late organogenesis or fetal period caused
      chromosome damage and significant depletion in the fetal haemopoietic progenitor
      cells and led to haematological disorders in the adults. The present paper
      reviews the experimental findings on the effect of pre-natal irradiation on the
      fetal haemopoietic system and its long-term consequences.

PMID- 12814922
TI  - Pulmonary complications following bone marrow transplantation.
AB  - Pulmonary complications account for significant morbidity and mortality in
      patients following bone marrow transplants (BMT). They are distinct from other
      immunosuppressed patients in that there is a predictable course of
      immunosuppresion and therefore of likely pulmonary complications. This is
      important when interpreting abnormal radiology as the predictable time course
      will enable narrowing the differential diagnoses to certain pulmonary
      complications that characteristically occur at a particular time following BMT.
      Early recognition and correct treatment of the pulmonary complications should
      minimize the significant mortality and morbidity. This review aims to discuss the
      role of radiology in the diagnosis and management of pulmonary complications
      following BMT.

PMID- 12814923
TI  - Deep venous thrombosis associated with protein C and/or S deficiency: management
      with catheter-directed thrombolysis.
AB  - We performed this study to evaluate the efficacy of catheter-directed
      thrombolysis with urokinase in treating acute symptomatic iliofemoral deep venous
      thrombosis associated with protein C and/or S deficiency. A total of 42
      consecutive patients with deep venous thrombosis were seen between September 2000
      and August 2002. Of these, catheter-directed thrombolysis via the popliteal vein
      was performed in 5 patients (11.9%) with acute iliofemoral deep venous thrombosis
      associated with protein C and/or S deficiency. Average duration of symptoms was
      4.2 days (range, 1-7 days). The average urokinase dose was 2.7 million IU (range,
      0.6 million to 7.0 million IU) infused over an average of 33.1 h (range, 16-67
      h). Lysis was complete in all five treated cases. Two cases had underlying iliac
      venous stenoses (>50%) that were treated with angioplasty and stent placement. In
      one patient in whom recanalization of a right iliac vein occlusion was
      successful, thrombosis occurred in the treated vein within 3 weeks of
      intervention despite full anticoagulation therapy, and further intervention was
      required. There were no complications or clinically detectable pulmonary emboli.
      The technical and clinical success rates were 100%. This initial experience
      suggests that catheter-directed thrombolysis for treatment of acute symptomatic
      iliofemoral deep venous thrombosis associated with protein C and/or S deficiency
      is safe and effective.

PMID- 12814924
TI  - Contrast enhancement patterns of hepatic tumours during the vascular phase using
      coded harmonic imaging and Levovist to differentiate hepatocellular carcinoma
      from other focal lesions.
AB  - The purpose of the study was to assess contrast enhancement patterns of hepatic
      tumours during the vascular phase using contrast-enhanced ultrasound and Levovist
      to differentiate hepatocellular carcinoma from other hepatic tumours. 89 hepatic
      tumours in 82 consecutive patients were evaluated using coded harmonic ultrasound
      imaging. The procedure used a phase inversion harmonic technique and coded
      technology. We observed images for 2 min from the beginning of the administration
      as the vascular phase using continuous transmission and intermittent
      transmissions of 1 s or 2 s. The contrast agent Levovist was administered
      intravenously as a bolus infusion of 2.5 g. Tumour vessels with flow spreading
      into the tumour and/or homogeneously stained hyperechoic images were observed in
      34 of the 41 hepatocellular carcinomas (sensitivity, 82.9%; specificity, 93.8%).
      Peripheral enhancements were characteristic of intrahepatic cholangiocarcinoma
      and metastatic hepatic tumours (sensitivity, 60.0% and 83.3%; specificity, 65.5%
      and 76.4%, respectively). Pooling at the periphery or throughout the tumour was
      apparent only in haemangioma (sensitivity, 76.5%; specificity, 100%). A tortuous
      feeding artery and spoke-like vascularization were evident only in the two focal
      nodular hyperplasias. Contrast-enhanced ultrasound using coded harmonic
      ultrasound imaging and Levovist provided detailed information about tumour
      vascularity and contrast enhancement patterns in hepatic tumours.

PMID- 12814925
TI  - Radiation doses for barium enema and barium meal examinations in Ireland:
      potential diagnostic reference levels.
AB  - Wide variations in patient dose for the same examinations have been demonstrated
      by several studies throughout Europe. By investigating patient dose, variations
      can be acknowledged, causal agents sought and the necessary adjustments made.
      Diagnostic reference levels (DRLs) provide a framework with which dose levels
      from individual hospitals are compared, and when exceeded, corrective actions can
      be taken where appropriate. This study aimed to establish DRLs for barium enema
      and barium meal examinations in Ireland. Measurements were recorded using a dose
      area product meter in 12 hospitals representing 33% of relevant hospitals.
      Results demonstrated wide mean hospital dose variation, by up to a factor of 7.8
      and 4.2 for barium enema and barium meal examinations, respectively. Minimum and
      maximum individual patient dose values varied by a factor of 45 for barium enemas
      and 90 for barium meal examinations. Reasons for dose variations were complex,
      but major factors for both examinations were fluoroscopy time, secondary
      radiation grid type and level of filtration. Some examination-specific factors
      were also noted. DRLs, established using the quantity dose-area product, were
      calculated to be 47 Gy cm(2) for barium enemas and 17 Gy cm(2) for barium meal
      examinations. Although the DRL value for barium meals was the same as the
      reference value established in the UK for that examination in 1996, the barium
      enema DRL in this study was 45% higher than the relevant UK value.

PMID- 12814926
TI  - Survey of posteroanterior chest radiography in The Netherlands: patient dose and
      image quality.
AB  - Council Directive 97/43/Euratom (Medical Exposure Directive) states that member
      States of the European Union shall promote the establishment and use of
      diagnostic reference levels for radio-diagnostic examinations. Dose surveys can
      form the basis for the establishment of diagnostic reference levels. In view of
      the implementation of the Medical Exposure Directive in the Netherlands, a survey
      of dose and image quality has been performed for posteroanterior (PA) chest
      radiography in 2001. In this survey, 25 participants were selected from a list of
      175 Dutch hospitals, whereas in a previous PA chest survey (about 10 years ago)
      participation was voluntary and participants came predominantly from the south
      western part of the Netherlands. For conventional screen-film PA chest
      radiography, the present results for patient dose and image quality are quite
      similar to those results from the previous survey. The fraction of conventional X
      ray systems utilizing lung compensation filters has remained approximately the
      same. For dedicated digital chest radiography systems, image quality is better
      than for conventional systems, but doses vary and can assume relatively high
      values. The results indicate that there are still possibilities for dose
      reduction, without loss of image quality. The 75 percentile value of the entrance
      surface dose distribution is approximately 0.13 mGy.

PMID- 12814927
TI  - Effective techniques for reduction of radiation dosage to patients undergoing
      invasive cardiac procedures.
AB  - The goal of this study was to improve radiation dose reduction techniques in
      invasive cardiology and after patients' radiation data had approached minimal
      levels, to evaluate predictors of their radiation exposure resulting from
      invasive cardiac procedures. Over the course of 1 year (and 1996 procedures) we
      minimized cinegraphic frames and runs, as well as fluoroscopy time, and trained
      ourselves to achieve effective fluoroscopy-saving positioning of blinds and
      filters toward the regions of interest. We were consequently able to reduce the
      mean dose-area products (DAP) for coronary angiography and angioplasty, combined
      interventions, high-frequency rotational atherectomy, and excimer laser
      angioplasty: from levels of 53.9 Gy cm(2), 79.6 Gy cm(2), 112.3 Gy cm(2), 119.4
      Gy cm(2), and 168.0 Gy cm(2) as currently reported in the literature, to 12.9 Gy
      cm(2), 13.3 Gy cm(2), 25.9 Gy cm(2), 33.0 Gy cm(2), and 27.1 Gy cm(2),
      respectively. The mean DAP due to interventions in acute myocardial infarction
      was 38.3 Gy cm(2). DAP was influenced by body mass index, complexity of coronary
      artery disease, tube angulation, documented structure, coronary recanalization,
      emergency circumstances, and the percutaneous transluminal coronary angioplasty
      (PTCA) target vessel involved, but not by stent implantation. By favouring
      radiation-reducing cranial posteroanterior views over standard left anterior
      oblique views for visualization of the left anterior descending and the diagonal
      artery, we consequently achieved mean PTCA-DAPs of 10.4 Gy cm(2) and 8.6 Gy
      cm(2), respectively: levels significantly lower than those for PTCA of the right
      coronary artery (13.3 Gy cm(2)), left circumflex artery (13.7 Gy cm(2)), and
      obtuse marginal branch (16.9 Gy cm(2)). In conclusion, enhanced knowledge of
      radiation dose-reduction techniques significantly reduces patient radiation
      hazards in invasive cardiology.

PMID- 12814928
TI  - Iridium-192 implantation for T1 and T2a carcinoma of the tongue and floor of
      mouth: retrospective study of the results of treatment at the Royal Berkshire
      Hospital.
AB  - Carcinomas of the tongue and floor of mouth are relatively rare tumours, which
      may be treated using several modalities. We reviewed the results of iridium wire
      implants performed at the Royal Berkshire Hospital between 1994 and 2000. 24
      patients had iridium wire implants as primary treatment for tongue and floor of
      mouth cancers. Four patients were treated after excision biopsy with close or
      involved margins. One patient was treated for a recurrence after surgery. The
      median age at treatment was 61 years. There were 18 men and 11 women. 21 patients
      had tumours of the tongue and eight of the floor of mouth. 13 had T1 tumours and
      11 had T2a tumours. The median follow up was 42 months. The primary tumour was
      controlled in 22 of the 29 patients by the implant alone. Of the seven patients
      with local recurrence four were successfully salvaged with surgery. The
      acturarial 2 year survival rates were: overall survival 81%, disease specific
      survival 91%, local recurrence free survival 85% and nodal relapse free survival
      76%. The recorded complication rate was low, one patient developing radionecrosis
      of the mandible at 7 years post implant. We believe these results show that
      brachytherapy remains a treatment option for patients with early tongue carcinoma
      with a high rate of local control and low toxicity.

PMID- 12814929
TI  - Radiation dose to the lens of eye and thyroid gland in paranasal sinus multislice
      CT.
AB  - CT has become an established examination in the evaluation of the paranasal
      sinuses. Until recently this was achieved by the direct coronal technique on
      conventional and single slice helical scanners. With the advent of multislice
      technology, thin slice axial CT with excellent coronal and sagittal
      reconstructions is now the norm. We describe a study designed to evaluate the
      radiation dose to the lens of the eye and thyroid gland in the axial and coronal
      planes on a Siemens Volume Zoom quad slice scanner at 140 kV and effective mAs of
      100 using 1 mm collimation. Thermoluminescent dosimeters were placed on the
      eyelid and thyroid gland of 29 patients scanned axially in the supine position
      and a further 28 patients scanned coronally in the prone position with gantry
      tilt. The results show mean doses of 35.1 mGy (lens) and 2.9 mGy (thyroid gland)
      in the coronal plane compared with 24.5 mGy (lens) and 1.4 mGy (thyroid gland) in
      the axial plane. Results obtained from a head phantom and from using the ImPACT
      CT dose calculator were comparable. The kV and mAs were then reduced to 120 and
      40, respectively, and the axial study repeated using the head phantom and
      predicted doses using the ImPACT CT dose calculator. The low dose scanning
      technique revealed a lens dose of 9.2 mGy and thyroid dose of 0.4 mGy. The eye
      dose on a multislice scanner is still substantially less than the threshold dose
      of 0.5-2 Gy for detectable lens opacities. These results indicate that, in
      addition to the established perceived advantages of multislice axial sinus CT,
      i.e. patient comfort, no artefact from dental amalgam and reproducible true
      coronal images, should be included a decreased radiation dose to both the eye
      lens and thyroid gland compared with direct coronal scanning.

PMID- 12814930
TI  - Tentorial schwannoma: a case report.
AB  - A rare case of tentorial schwannoma in a 29-year-old male is described. The
      schwannoma was located within the leaves of the tentorium. MRI showed a wedge
      shaped enhancing tumour. Exact nerve of origin of the tumour could not be
      identified. We speculate that the tumour arose from the tentorial branch of the
      trigeminal nerve. The literature concerning intracranial schwannoma unrelated to
      a major cranial nerve is reviewed.

PMID- 12814931
TI  - Intraductal injection of the breast: a potential pitfall of radioisotope occult
      lesion localization.
AB  - The use of radioisotope for the localization of occult breast lesions (ROLL) has
      been advocated in preference to wire guided excision as it allows reduced
      excision volume and better lesion centering. However, as this technique is new,
      potential complications are unknown. In 2 out of 38 ROLL procedures performed at
      our institution, intraductal injection of isotope has occurred. This was
      diagnosed on check mammography as non-ionic iodinated contrast was mixed with the
      isotope. In one of these cases conversion to wire localization was required.

PMID- 12814932
TI  - An unusual cause of tachycardia.

PMID- 12814933
TI  - Tissue Remodeling. Proceedings of a symposium. Aims, Iowa, USA. August 1-4, 2002.

PMID- 12814934
TI  - Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta.
AB  - Transforming growth factor-beta (TGF-beta), a key player in a large variety of
      physiological and disease processes, signals through transmembrane receptor
      serine/threonine kinases to activate novel signaling intermediates called Smad
      proteins, which then modulate transcription of target genes. We have utilized
      mice with a targeted deletion of Smad3, one of two homologous proteins involved
      in signaling from TGF-beta/activin, to investigate the function of this
      particular pathway in transducing such effects of TGF-beta. The dramatic results
      of the absence of Smad3 on parameters of healing of cutaneous wounds, such as
      reepithelialization and influx of inflammatory cells, as well as on fibrosis as
      modeled by radiation fibrosis of skin in mice, suggest that signaling flux
      through Smad3 is critical for chemotactic activity of TGF-beta, inhibitory
      effects of TGF-beta on keratinocyte proliferation and migration, and
      chemoattraction and elaboration of extracellular matrix by fibroblasts in
      fibrotic diseases. We recently identified a novel molecule, TLP for TRAP-1-like
      protein, which selectively interferes with Smad3 signaling, and are currently
      investigating whether levels of this protein might be altered in disease to
      change the relative flow of information from Smad2 and Smad3.

PMID- 12814935
TI  - TIAF1 participates in the transforming growth factor beta1--mediated growth
      regulation.
AB  - TGF-beta induces growth suppression and apoptosis of various types of cells, but
      supports fibroblast growth. We previously isolated TIAF1 (TGF-beta1-induced
      antiapoptotic factor 1), which protects murine L929 fibroblasts from TNF
      cytotoxicity. Here, we show that TIAF1 induced growth inhibition and apoptosis of
      monocytic U937 and other types of cells. In contrast, like TGF-beta1, TIAF1
      supported transforming growth of L929 fibroblasts. TIAF1 increased the expression
      of p53, Cip1/p21, and Smad proteins; suppressed ERK phosphorylation; and altered
      TGF-beta1-mediated Smad2/3 phosphorylation in U937 cells. Antisense TIAF1 mRNA
      significantly enhanced the proliferation of mink lung Mv1Lu epithelial cells.
      Together, these observations indicate that TIAF1 participates in the TGF-beta
      mediated growth regulation.

PMID- 12814936
TI  - TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological
      convertase.
AB  - EGF family growth factors, including transforming growth factor-alpha (TGFalpha),
      amphiregulin (AR), and heparin-binding EGF (HB-EGF), are invariably expressed as
      transmembrane precursors that are cleaved at one or more sites in the
      extracellular domain to release soluble growth factor. Considerable attention has
      focused on the identification of proteases responsible for these processing
      events. We previously implicated tumor necrosis factor-alpha converting enzyme
      (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane
      precursor, proTGFalpha. Here, we review our findings that primary keratinocytes
      from Tace(deltaZn/deltaZn) mice, which express a nonfunctional TACE, released
      dramatically lower levels of soluble TGFalpha compared to their normal
      counterparts, even though TGFalpha mRNA and cell-associated protein levels were
      similar in the two cell populations. Restoration of TACE activity in
      Tace(deltaZn/deltaZn) cells increased shedding of TGFalpha species, including the
      mature, 6-kDa protein. Further, exogenous TACE enzyme accurately cleaved the N
      terminal processing site of proTGFalpha in cell lysates, as well as both
      physiologic sites of a soluble proTGFalpha ectodomain. TACE also accurately
      cleaved peptide substrates corresponding to the processing sites of several
      additional EGF family members, and restoration of TACE activity enhanced the
      shedding of soluble AR and HB-EGF proteins from Tace(deltaZn/deltaZn) cells.
      Finally, reduction of functional TACE gene dosage greatly exacerbated the open
      eye defect of Egfr(wa-2/wa-2) newborns, which is regulated by redundant actions
      of several EGF family ligands. The implications of these results for the biology
      of the EGF family and TACE are discussed.

PMID- 12814937
TI  - Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in
      human placenta.
AB  - The epidermal growth factor receptor (EGFR) and related family members (ERBB2,
      ERBB3, and ERBB4) previously have been shown to play pivotal roles in the
      development of female reproductive tissues, in blastocyst implantation, and in
      placental differentiation. We have cloned and sequenced several naturally
      occurring alternative transcripts of the human and mouse EGFR genes, which encode
      novel receptor isoforms containing varying portions of the extracellular ligand
      binding domain, but lacking the transmembrane and cytoplasmic domain sequences.
      The human 1.8-kb and 3-kb alternative EGFR transcripts encode secreted 60-kDa and
      cell surface-associated 110-kDa EGFR isoforms, respectively. We have developed
      quantitative ribonuclease protection assays to study the expression of these
      alternative transcripts in human tissues. Similar to the full-length EGFR mRNAs,
      the highest expression level of these alternative transcripts occurs in placenta.
      We speculate that both of these EGFR isoforms may be important regulators of EGF
      mediated cell growth and differentiation in human placenta.

PMID- 12814938
TI  - The roles of activin in cytoprotection and tissue repair.
AB  - Activin is a member of the transforming growth factor beta family of growth and
      differentiation factors. Initially discovered as a protein that stimulates
      release of follicle-stimulating hormone, it is now well accepted as an important
      regulator of cell growth and differentiation. Most interestingly, a series of
      previous studies have revealed novel roles of activin in inflammation and repair.
      Our own results have provided evidence for an important function of activin in
      cutaneous wound repair as well as in neuroprotection, and these data will be
      summarized and discussed in this chapter.

PMID- 12814939
TI  - Tissue growth and remodeling of the embryonic and adult adrenal gland.
AB  - The adrenal gland provides a model system for the study of tissue remodeling in
      endocrine physiology. For example, proper adrenal development requires
      proliferation of the adrenogonadal primordia, separation of adrenal and gonadal
      precursors, and cell migration that unites the adrenal cortex and adrenal
      medulla. In the adult, normal adrenal function is assured by the adrenal gland's
      unique capacity for growth in response to both tissue injury and physiological
      demand. Identification of the molecular and genetic programs underlying tissue
      remodeling in the adrenal is important for understanding basic aspects of
      development and regeneration, as well as adrenal disease. Here, we will highlight
      the roles that nuclear receptors and pituitary hormones play in regulating fetal
      adrenal development and adult adrenal growth. In addition, we will review the
      most current data on how extracellular signaling pathways are coupled to the
      function of these important regulators of adrenal development and function.

PMID- 12814940
TI  - The human placenta remodels the uterus by using a combination of molecules that
      govern vasculogenesis or leukocyte extravasation.
AB  - After fertilization, the next major hurdle for human reproduction is trophoblast
      differentiation, which is required for implantation, followed in lockstep by
      rapid assembly of these embryonic cells into a functional placenta. During this
      process, cytotrophoblast stem cells invade the uterus, anchoring the conceptus to
      the mother and establishing blood flow to the placenta. Cytotrophoblast invasion
      is actually a differentiation process that yields cells with many unusual
      attributes, that is, their tumor-like ability to invade the uterus and engraft
      maternal blood vessels. We discovered that once cytotrophoblasts commit to
      invasion they turn on expression of adhesion receptors characteristic of
      endothelium. They also begin to express and activate matrix metalloproteinase-9.
      Together, these phenotypic changes facilitate invasion while enabling
      cytotrophoblasts to present an endothelium-like surface to maternal blood.
      Currently, we are trying to understand the factors that play a role in
      cytotrophoblast differentiation/invasion. In keeping with the vascular
      characteristics that differentiated cytotrophoblasts assume, our recent data
      suggest that the key regulators include an unusual subset of vascular endothelial
      growth factor family members that play important roles in conventional
      vasculogenesis/angiogenesis. Surprisingly, we also discovered that these cells
      express functional l-selectin, which mediates neutrophil rolling and tethering,
      under shear stress, on inflamed endothelium. Trophoblast l-selectin likely
      interacts with carbohydrate selectin ligands that are upregulated on uterine
      glandular epithelium during the window of receptivity. Together, these data
      suggest that differentiating cytotrophoblasts have co-opted portions not only of
      vasculogenesis, but also of the process that facilitates leukocyte emigration
      from the blood into tissues, additional evidence of these cells' amazing
      plasticity.

PMID- 12814941
TI  - Chorioallantoic morphogenesis and formation of the placental villous tree.
AB  - The placenta is a highly specialized organ whose primary function is to promote
      the exchange of nutrients and oxygen between maternal and fetal blood, essential
      for survival and growth of the baby. The surface area for nutrient transport is a
      highly convoluted villous structure that forms by branching morphogenesis. In
      mice, this process begins after embryonic day 8.5, following attachment of
      allantoic mesoderm to the chorion, and continues through the end of gestation.
      Gene targeting studies in mice have identified a large number of genes that are
      essential for chorioallantoic development to give rise to the layer of the
      placenta called the labyrinth. Collectively, these studies reveal that a number
      of signaling pathways regulate four distinct phases of labyrinth development:
      chorioallantoic attachment (involving VCAM1 and its receptor alpha4 integrin,
      Bmp5/7, and Wnt7b, as well as the cochaperone Mrj), initiation of branching
      (involving the Gcm1 transcription factor to select sites of branch initiation),
      extension of villous branching (involving FGF, EGF, and HGF/Met signaling,
      through the Grb2/Sos1/Mek1/p38alpha MAPK pathway), followed by vascularization of
      the villous tree. The restricted expression and/or action of the signaling
      components indicate that a series of intercellular interactions regulate
      chorioallantoic development.

PMID- 12814942
TI  - Tissue involution and the acute phase response.
AB  - After their roles in reproduction are completed, the mass of the uterus and the
      mammary gland decrease rapidly by the process of involution that involves an
      ordered series of events including apoptosis, neutrophil entry, the release of
      degradative enzymes, and phagocytosis of cellular debris. The acute phase
      proteins are produced by the liver and other tissues in response to inflammation
      or a toxic challenge. Uterocalin (SIP24/24p3) is one of these proteins. During
      involution, the mammary gland and uterus express high levels of uterocalin that
      reach an average of 0.2-0.5% of the total extractable protein at its peak.
      Uterocalin and its orthologues have been demonstrated in vitro to (1). bind
      certain fatty acids and (2). specifically induce apoptosis in neutrophils and
      other leukocytes. The period of uterocalin expression during involution is
      consistent with the hypothesis that one of its physiological roles is to induce
      apoptosis of invading neutrophils and delay the entry of neutrophils into the
      tissue until the second phase of involution. Interestingly, it has been shown
      that uterocalin expression remains higher in primiparous gland than in virgin
      glands after the pregnant glands have completely involuted. This observation and
      the known protective effect of early pregnancy on later development of breast
      cancer suggest that the ability of uterocalin to induce apoptosis in neutrophils
      might also decrease oxidative and carcinogenic activity in the gland and result
      in a lower mutation rate and thus a lower probability of cancer in the
      primiparous gland.

PMID- 12814943
TI  - How proteases regulate bone morphogenesis.
AB  - Matrix metalloproteinases (MMPs) degrade most components of the extracellular
      matrix (ECM), as well as many non-ECM molecules. MMPs participate in (1).
      degradation of ECM to allow cell migration; (2). alteration of the ECM
      microenvironment resulting in alteration in cellular behavior; (3). modulation of
      biologically active molecules by direct cleavage or release from ECM stores; (4).
      regulation of the activity of other proteases; and (5). cell attachment,
      proliferation, differentiation, and apoptosis. We have sought to understand the
      role of MMPs during development and tissue repair in transgenic mice.
      Endochondral bone formation presents a particularly interesting developmental
      challenge. During this process, an avascular tissue (cartilage) is converted into
      one of the most highly vascularized tissues (bone) in the vertebrate body.
      Ossification begins with invasion of the calcified hypertrophic cartilage by
      capillaries. Apoptosis of the terminal hypertrophic chondrocytes, degradation of
      the cartilage matrix, and deposition of bone matrix by osteoblasts accompanies
      neovascularization of the growth plate. Remodeling of ECM results in a cavity
      filled with vascular channels containing hematopoietic cells. Our results reveal
      that MMP9, MMP13, and vascular endothelial growth factor are key regulators for
      the remodeling of the skeletal tissues. They coordinate not only matrix
      degradation, but also the recruitment and differentiation of endothelial cells,
      osteoclasts, chondroclasts, and osteoprogenitors.

PMID- 12814944
TI  - Cell migration and programmed cell death of Drosophila germ cells.
AB  - Cell migration and programmed cell death are essential components of animal
      development and homeostasis, and the germ cells of Drosophila provide a simple
      genetic system to study the molecular mechanisms that govern these important
      cellular processes. Detailed descriptions of germ cell migration in Drosophila
      were accomplished long ago, but most genetic and molecular analyses of the
      process have occurred within the past 10 years. A few of the genes required for
      germ cell migration have been identified, and a very interesting picture is
      emerging. However, a process as complex as cell migration must involve the
      functions of many more molecules. In addition, cell migration and cell death
      mechanisms are often linked, as it is important to eliminate cells that are
      misplaced and could present a danger to the organism. In Drosophila, genes
      involved in germ cell migration can also affect programmed cell death. Currently,
      very little is known about how germ cells ectopic to the gonads are eliminated.
      To date, only four genes have been reported with roles in germ cell death, and
      three of these have additional functions in germ cell pathfinding. The nature of
      the cell death program has not been elucidated. Here, I provide a brief review of
      Drosophila germ cell migration and programmed cell death at both the descriptive
      and molecular levels. Many questions remain to be answered, but advances made in
      recent years are providing useful insights into these critical biological
      phenomena.

PMID- 12814945
TI  - Differentiation and morphological integration of neural progenitor cells
      transplanted into the developing mammalian eye.
AB  - Transplantation of neural stem/progenitor cells has been proposed as a novel
      approach for the replacement and repair of damaged CNS tissues. We have evaluated
      the influence of the host cellular microenvironment upon the survival,
      differentiation, and integration of neural progenitor cells transplanted into the
      CNS. Using this approach, we have investigated the fate of neural progenitor
      cells in vivo following transplantation into the developing mammalian eye. Murine
      brain progenitor cells (mBPCs) isolated from neonatal mice expressing the green
      fluorescent protein (GFP) transgene were transplanted into the eyes of Brazilian
      opossums (Monodelphis domestica). Monodelphis pups are born in an extremely
      immature, fetal-like state. The eyes of neonatal pups provide a fetal-like
      environment in which to study cellular interactions between host tissues and
      transplanted neural progenitor cells. mBPCs were transplanted by intraocular
      injection in hosts ranging in age from 5 days postnatal to adult. The
      transplanted cells were easily identified because of their GFP fluorescence.
      Extensive survival, differentiation, and morphological integration of mBPCs
      within the host tissue was observed. We found that the younger retinas provided a
      more supportive environment for the morphological integration of the transplanted
      mBPCs. Cells with morphologies characteristic of specific retinal cell types were
      observed. Moreover, some transplanted mBPCs were labeled with antibodies
      characteristic of specific neural/retinal phenotypes. These results suggest that
      the host environment strongly influences progenitor cell differentiation and that
      transplantation of neural progenitor cells may be a useful approach aimed at
      treating degeneration and pathology of the CNS.

PMID- 12814946
TI  - Role of collagen type II and perlecan in skeletal development.
AB  - The cartilage extracellular matrix is composed of a dense collagen network that
      entraps a range of other specialized proteins important for the proper formation
      and function of the tissue. Loss of two abundant cartilage components, type II
      collagen and perlecan, has drastic effects on skeletal development. Both collagen
      II and perlecan mutants have severe and lethal chondrodysplasia characterized by
      disorganized growth plate, lack of collagen network, defective endochondral bone
      formation, and abnormal intervertebral disk development. To test whether the
      reduced collagen density in the perlecan-null cartilage is due to enhanced
      activity of collagen-degrading proteinases, we have analyzed gelatinase
      expression and activity in the mutant tissue. Immunohistochemical analysis
      revealed a weak, but clear, expansion of MMP-9 deposition into the hypertrophic
      zone of the perlecan-null growth plate. However, in situ and SDS-PAGE zymography
      showed that the activity of gelatinases (MMP-2 and MMP-9) is not altered in
      perlecan-null cartilage, suggesting that they are not primarily linked to the
      reduced fibrillar network observed in the mutant. Likewise, intercrossing of
      perlecan mutants onto an MMP-9-null background could not rescue the
      ultrastructural abnormalities of the perlecan-deficient cartilage.

PMID- 12814947
TI  - Remodeling of the microenvironment by aggressive melanoma tumor cells.
AB  - A necessity for development and tumor progression is a blood supply formed by
      vasculogenic and/or angiogenic events, involving the cooperative interactions of
      cells with their microenvironment. Based on the recent characterization of
      vasculogenic mimicry by aggressive melanoma cells, particularly their ability to
      express VE (vascular endothelial)-cadherin, TIE-1, and EphA2, current studies
      have focused on the molecular signals deposited by these cells as they remodel
      their microenvironment. The experimental approach utilizes unique three
      dimensional collagen matrices preconditioned by metastatic melanoma cells, which
      contain laminin 5 gamma2 chain-enriched tracks with promigratory cleavage
      fragments produced by cooperative interactions with specific matrix
      metalloproteinases (MMPs). The results demonstrate that the collagen matrices
      preconditioned by the metastatic cells induce poorly aggressive melanoma cells to
      express, for the first time, key angiogenic/vasculogenic/matrix-remodeling genes.
      Treatment of aggressive melanoma cells with an MMP inhibitor resulted in the
      inhibition of vasculogenic mimicry-associated genes in these tumor cells and
      abrogation of the inductive effects of the preconditioned matrix on poorly
      aggressive melanoma cells. These observations illustrate the remarkable influence
      of the microenvironment on the phenotype of melanoma cells and may provide new
      perspectives on tumor cell plasticity and unique treatment strategies.

PMID- 12814948
TI  - Notch signaling in primary endothelial cells.
AB  - The Notch family of cell-surface receptors has been proposed to regulate cell
      fate decisions by modulating the ability of each cell to respond to environmental
      cues. In vertebrates, gain-of-function and loss-of-function studies have
      demonstrated a requirement for Notch signaling for proper patterning of the
      vasculature during embryogenesis. To examine the molecular mechanisms by which
      Notch regulates vascular development, we analyzed changes in gene expression in
      response to Notch signaling. Notch signal transduction and function were assessed
      in primary human endothelial cells isolated from the dermal microvasculature of
      neonates, HMVECd. We demonstrate that HMVECd cells express a heterodimeric form
      of endogenous Notch4 on their cell surface. Using an in vitro coculture assay, we
      found that Delta4 can function as a ligand for Notch4 in HMVECd cells. Moreover,
      ectopic expression of an activated allele of Notch4 upregulated the expression of
      Delta4, suggesting that there may be a regulatory loop between Notch4 and its
      ligand, Delta4. Notch4 activation also induced the expression of the
      transcriptional repressors, HES1, HERP1, and HERP2, as well as ephrinB2, an
      angiogenic factor proposed to be involved in arterial/venous endothelial cell
      specification.

PMID- 12814949
TI  - Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth
      and tumor-associated angiogenesis.
AB  - Macrophage migration inhibitory factor (MIF) functions as a pluripotent cytokine
      involved in broad-spectrum pathophysiological events in association with
      inflammation and immune responses. Several reports, including ours, have
      suggested that MIF is also involved in tumorigenesis; however, its precise role
      has not been fully investigated. We examined the effectiveness of anti-MIF
      antibodies on tumor growth and tumor-associated angiogenesis using murine colon
      cancer cell line, colon 26. We observed a significant inhibition of growth of
      tumors embedded on the back of BALB/c mice by treatment with anti-MIF antibodies.
      Next, we implanted a Millipore chamber filled with colon cancer cells in the
      subcutaneous fascia of the flanks of mice and then treated them with anti-MIF
      antibodies. We found that angiogenesis was markedly suppressed within the region
      of the subcutaneous fascia that was in contact with the chamber. To further
      assess the role of MIF in tumorigenesis, we established MIF transgenic mice,
      which demonstrated that tumor growth and the associated angiogenesis were
      significantly enhanced in comparison with control mice.

PMID- 12814950
TI  - ADAMTS1: a matrix metalloprotease with angioinhibitory properties.
AB  - Neovascularization is a hallmark of cancer progression. Suppression of the
      angiogenic response in tumors has been associated with inhibition and even
      regression of total tumor mass. Therefore, the derivation of synthetic or natural
      products that could interfere with proangiogenic signaling pathways can greatly
      impact cancer therapy. Using the antiangiogenic motifs in thrombospondin-1, we
      have recently cloned METH1/ADAMTS1, a secreted metalloproteinase with three
      thrombospondin-1, and shown that the protein inhibits endothelial cell
      proliferation in vitro and blocks the neovascular response induced by growth
      factors in vivo. The mechanism of action responsible for these events has not
      been elucidated. In this report, we present evidence to support two effects of
      METH1/ADAMTS1 that impact proangiogenic signaling events. ADAMTS1 binds to VEGF
      and dampens VEGFR2 phosphorylation. The ability of ADAMTS1 to bind VEGF and
      functionally inactivate VEGFR2 is reversible as dissociation of the complex
      results in active growth factor. A second activity of ADAMTS1 requires the
      catalytic domain as a single point mutation in the metalloproteinase domain
      renders the protein inactive in tumor xenograft assays. The emerging theme is
      that both domains are likely required for the antiangiogenic/antitumor activities
      of ADAMTS1.

PMID- 12814951
TI  - Genetic analysis of hypoxia signaling and response in C elegans.
AB  - During normal development and homeostasis, animals use cellular and systemic
      strategies to adapt to changing oxygen levels. In mammals, hypoxic tissues
      secrete growth factors to induce angiogenesis, and individual cells increase
      anaerobic metabolism in order to sustain basic cellular functions. Many of these
      critical responses to decreased oxygen availability are regulated by the hypoxia
      inducible factors, dimeric transcriptional complexes consisting of alpha and beta
      subunits. HIFalpha proteins are specialized for hypoxia response, and oxygen
      levels regulate their stability and activity. The C. elegans hif-1 gene is
      orthologous to mammalian HIFalpha genes, and C. elegans has proven to be a
      powerful system for the study of hypoxia-inducible factor regulation and
      function. Mutants lacking hif-1 function are viable in normoxic or anoxic
      conditions, but they cannot adapt to hypoxia. Recent genetic analyses in C.
      elegans led to the identification of the evolutionarily conserved enzyme that
      hydroxylates HIFa in an oxygen-dependent manner. Once modified, HIFalpha binds
      the von Hippel-Lindau tumor suppressor protein and is targeted for proteasomal
      degradation. Here, we briefly review the characterization of C. elegans hif-1 and
      interacting genes, and discuss genetic strategies for studying hypoxia signaling
      and response.

PMID- 12814952
TI  - Comparative structure-function analysis of VEGFR-1 and VEGFR-2: What have we
      learned from chimeric systems?
AB  - Activation of vascular endothelial growth factor receptor-1 and -2 (VEGFR-1 and
      VEGFR-2) plays a critical role in vasculogenesis and angiogenesis. However, the
      mechanism by which activation of VEGFRs elicits these cellular events is not
      fully understood. We recently constructed chimeric receptors containing the
      extracellular domain of human CSF-1R/c-fms fused with the entire transmembrane
      and cytoplasmic domains of murine VEGFR-1 and VEGFR-2. Selective activation of
      chimeric VEGFR-2, but not chimeric VEGFR-1, stimulated endothelial cell growth,
      migration, and differentiation. Stimulation of cells coexpressing chimeric VEGFR
      1 and VEGFR-2 suppressed VEGFR-2-mediated endothelial cell growth. Site-directed
      mutagenesis demonstrated that tyrosines 799 and 1173 are required for VEGFR-2
      mediated endothelial cell growth and activation of PI3 kinase. Further site
      directed mutagenesis demonstrated that tyrosine 1212, located in the carboxyl
      tail of VEGFR-2, is required for the ligand-dependent autophosphorylation of the
      receptor and its ability to activate signaling proteins. Collectively, our
      results suggest that activation of VEGFR-1 and VEGFR-2 differentially regulates
      endothelial cell function and angiogenesis. Second, activation of VEGFR-2 is
      associated with many endothelial cell functions, including cell proliferation,
      migration, and differentiation. Third, activation of PI3 kinase by VEGFR-2
      regulates endothelial cell proliferation.

PMID- 12814953
TI  - Induction of vascular networks in adult organs: implications to proangiogenic
      therapy.
AB  - Most therapeutic proangiogenic approaches rely on the premise that a single
      factor (e.g., VEGF) can induce new vascular loops properly connected to the
      existing vasculature of an ill-perfused organ (e.g., the ischemic myocardium). To
      gain insights into VEGF-driven neovascularization in the adult, in general, and
      to uncover inherent obstacles in VEGF-based therapeutic angiogenesis, we have
      used a transgenic system for conditional "on" and "off" switching of VEGF
      expression in selected adult organs and analytical methods for three-dimensional
      visualization of the induced vascular network. VEGF induces massive accumulation
      of endothelial progenitor cells and their subsequent coalescence into new
      vascular loops. Continual ramification of the vasculature and fusion of adjacent
      vessels culminate in formation of hemangioma-like vessels. In the absence of
      guiding cues, abnormal branching patterns and random connections with the
      existing network are formed. Following cessation of the VEGF stimulus, the
      acquired network undergoes extensive hemodynamic remodeling acting to "normalize"
      its architecture. Premature withdrawal of VEGF leads to regression of most
      acquired vessels, thus challenging the utility of therapeutic approaches relying
      on short stimulus duration. Overproduction of VEGF leads also to highly
      disruptive edema, thereby emphasizing the need to uncouple VEGF-induced
      permeability from its angiogenic activity. This genetic switch system thus
      highlights remaining problems critical for the implementation of proangiogenic
      therapy.

PMID- 12814954
TI  - Sex allocation of females and hermaphrodites in the gynodioecious Geranium
      sylvaticum.
AB  - Seed production and patterns of sex allocation were studied in female and
      hermaphroditic plants in two gynodioecious populations of Geranium sylvaticum
      (Geraniaceae). Females produced more flower buds and seeds than hermaphrodites in
      one of the two study populations. The other female traits measured (pistil
      biomass, seed number per fruit, individual seed mass) did not differ between the
      gender morphs. The relative seed fitness of hermaphrodites differed between the
      study populations, with hermaphrodites gaining less of their fitness through
      female function in the population with a high frequency of females. However, the
      amount and size of pollen produced by hermaphrodites did not differ between
      populations. The number of flower buds was positively correlated with seed
      production in females, whereas in hermaphrodites a positive correlation between
      number of buds and seed production was found in only one of the two study
      populations. These results suggest that fitness gain through female function is
      labile in hermaphrodites of this species, and is probably affected by
      environmental factors such as the sex ratio of the population.

PMID- 12814955
TI  - Changes in the high-mountain vegetation of the Central Iberian Peninsula as a
      probable sign of global warming.
AB  - Aerial images of the high summits of the Spanish Central Range reveal significant
      changes in vegetation over the period 1957 to 1991. These changes include the
      replacement of high-mountain grassland communities dominated by Festuca
      aragonensis, typical of the Cryoro-Mediterranean belt, by shrub patches of
      Juniperus communis ssp. alpina and Cytisus oromediterraneus from lower altitudes
      (Oro-Mediterranean belt). Climatic data indicate a shift towards warmer
      conditions in this mountainous region since the 1940s, with the shift being
      particularly marked from 1960. Changes include significantly higher minimum and
      maximum temperatures, fewer days with snow cover and a redistribution of monthly
      rainfall. Total yearly precipitation showed no significant variation. There were
      no marked changes in land use during the time frame considered, although there
      were minor changes in grazing species in the 19th century. It is hypothesized
      that the advance of woody species into higher altitudes is probably related to
      climate change, which could have acted in conjunction with discrete variations in
      landscape management. The pronounced changes observed in the plant communities of
      the area reflect the susceptibility of high-mountain Mediterranean species to
      environmental change.

PMID- 12814956
TI  - Effects of benomyl and drought on the mycorrhizal development and daily net CO2
      uptake of a wild platyopuntia in a rocky semi-arid environment.
AB  - The effects of drought and the fungicide benomyl on a wild platyopuntia, Opuntia
      robusta Wendl., growing in a rocky semi-arid environment were assessed. Cladode
      phosphorus content, cladode water potential and daily net CO2 uptake were
      measured monthly in 2000 and 2001 before, during and after the summer rainy
      period. During 2000, the formation of new roots and new cladodes was severely
      suppressed in response to a prolonged drought, impairing the development of the
      symbiotic relationship between the arbuscular mycorrhizal (AM) fungi and the
      roots. Hence no effect of benomyl application was observed on daily carbon
      assimilation by this Crassulacean acid metabolism plant. During 2001, drought was
      interrupted, and new cladodes and roots were formed in response to rainfall.
      Benomyl was highly effective in suppressing root colonization by AM-fungi;
      however, daily C assimilation was reduced by benomyl application only in October.
      Thus, the inhibition of AM-fungal colonization by benomyl did not affect
      photosynthesis, water uptake and P uptake under prolonged drought.

PMID- 12814957
TI  - The conduct of in vitro and in vivo drug-drug interaction studies: a
      Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.
AB  - Current regulatory guidances do not address specific study designs for in vitro
      and in vivo drug-drug interaction studies. There is a common desire by regulatory
      authorities and by industry sponsors to harmonize approaches, to allow for a
      better assessment of the significance of findings across different studies and
      drugs. There is also a growing consensus for the standardization of cytochrome
      P450 (P450) probe substrates, inhibitors and inducers and for the development of
      classification systems to improve the communication of risk to health care
      providers and to patients. While existing guidances cover mainly P450-mediated
      drug interactions, the importance of other mechanisms, such as transporters, has
      been recognized more recently, and should also be addressed. This article was
      prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug
      Metabolism and Clinical Pharmacology Technical Working Groups and represents the
      current industry position. The intent is to define a minimal best practice for in
      vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to
      development (not discovery support) and to define a data package that can be
      expected by regulatory agencies in compound registration dossiers.

PMID- 12814958
TI  - Selectivities of human cytochrome P450 inhibitors toward rat P450 isoforms: study
      with cDNA-expressed systems of the rat.
AB  - The aim of this study was to determine the selectivities of chemical inhibitors
      for human cytochrome P450 (P450) isoforms toward the corresponding rat P450
      isoforms by using cDNA-expressed rat P450s (CYP1A2, CYP2A1, CYP2C6, CYP2C11,
      CYP2D2, CYP2E1, CYP3A1, and CYP3A2). Among the inhibitor probes for human P450s
      used in this study, only sulfaphenazole showed a selective inhibitory effect on
      the activity of the corresponding rat P450 isoform (CYP2C6). Furafylline also
      preferentially inhibited the activity of rat CYP1A2. However, methoxalen and
      ketoconazole more strongly inhibited the activities of other P450 isoforms than
      those of the corresponding rat P450 isoforms, CYP2A1 and CYP3A1/2, respectively.
      On the other hand, quinidine and aniline had little effect on the activities of
      the corresponding rat P450 isoforms, CYP2D2, and rat CYP2E1, respectively. These
      results suggest that chemical probes that have been used for human P450 isoforms
      do not always exhibit the same selectivity for the corresponding rat P450
      isoforms. However, it appears that sulfaphenazole can be used as a selective
      inhibitor for rat CYP2C6. In addition, furafylline may also be a relatively
      selective inhibitor for rat CYP1A2.

PMID- 12814959
TI  - Protein covalent binding of maxipost through a cytochrome P450-mediated ortho
      quinone methide intermediate in rats.
AB  - (3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H
      indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K
      channels and has potential to prevent and treat ischemic stroke. Following single
      intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was
      extractable from plasma with organic solvents. The unextractable radioactivity
      remained associated with the proteins (mostly albumin) after SDS-polyacrylamide
      gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at
      110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS
      204352, one major radioactive product was isolated and identified as a lysine
      adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass
      spectrometry and NMR analyses as well as by comparison with the synthetic analog,
      lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS
      204352 results from the displacement of the ring-fluorine atom of des-O-methyl
      BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal
      incubations of [14C]BMS-204352 resulted in low levels of covalent binding of
      radioactivity to proteins. This in vitro covalent binding required cytochrome
      P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A
      inhibitors ketoconazole and troleadomycin selectively prevented the covalent
      binding in vitro. Based on these observations, a two-step bioactivation process
      for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated
      O-demethylation leading to spontaneous release of HF and the formation of an
      ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the
      epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro
      des-O-methyl BMS-204352 lysine adduct.

PMID- 12814960
TI  - In vitro metabolism of the mammalian soluble epoxide hydrolase inhibitor, 1
      cyclohexyl-3-dodecyl-urea.
AB  - The metabolism of the soluble epoxide hydrolase (sEH) inhibitor, 1-cyclohexyl-3
      dodecyl-urea (CDU), was studied in rat and human hepatic microsomes. The
      microsomal metabolism of CDU enhanced sEH inhibition potency of the reaction
      mixture and resulted in the formation of several metabolites. During the course
      of this study, a sensitive and specific high-performance liquid chromatography
      with tandem mass spectrometry analytical method was developed to investigate
      simultaneously the production of these metabolites. In both rat and human hepatic
      microsomes, CDU was ultimately transformed into the corresponding omega
      carboxylate; however, the rodent tissue appeared to perform this transformation
      more rapidly. After a 60-min incubation in rat hepatic microsomes, the percentage
      of residual CDU, the omega-carboxylate, and the intermediary omega-hydroxyl were
      about 20%, 20%, and 50%, respectively. Carbon monoxide inhibited the metabolism
      of CDU by rat hepatic microsomes, suggesting that the initial step is catalyzed
      by cytochrome P450. Further metabolism was enhanced by the addition of NAD,
      suggesting that dehydrogenases are associated with intermediate metabolic steps.
      Regardless, the ultimate product of microsomal metabolism, 12-(3-cyclohexyl
      ureido)-dodecanoic acid, is also an excellent sEH inhibitor with several hundred
      fold higher solubility, supporting the hypothesis that CDU has prodrug
      characteristics. These findings will facilitate the rational design and
      optimization of sEH inhibitors with better physical properties and improved
      metabolic stability.

PMID- 12814961
TI  - Two new polymorphisms of the FMO3 gene in Caucasian and African-American
      populations: comparative genetic and functional studies.
AB  - To characterize the contribution of the human flavin-containing monooxygenase
      form 3 (FMO3) in the metabolism and disposition of drugs and xenobiotics, we
      determined the single nucleotide polymorphisms in the coding region and adjacent
      splice junctions of FMO3 in 134 African Americans and 120 Caucasians from the
      United States. In the regions examined, DNA resequencing or high throughput
      MassEXTEND studies coupled with mass spectrometric genotyping showed that 12
      sites of variation were present. Three variants encoding synonymous mutations and
      four polymorphisms were observed in the noncoding region. Another three variants,
      Lys158-FMO3, Met257-FMO3 and Gly308-FMO3, previously reported in similar
      populations, were prominent polymorphisms. Two new polymorphisms, His132-FMO3 and
      Pro360-FMO3, were identified in this study. Both variants were found only in
      African Americans. To evaluate the effect of the amino acid substitutions on the
      function of FMO3, each amino acid substitution was introduced by site-directed
      mutagenesis into a wild-type FMO3 cDNA. Selective functional activity was studied
      with methimazole, trimethylamine, and 10-(N,N-dimethylaminopentyl)-2
      (trifluoromethyl) phenothiazine. Both His132-FMO3 and Pro360-FMO3 variants were
      able to metabolize the substrates examined. Compared with wild-type FMO3, the
      His132-FMO3 was less catalytically efficient. The His132-FMO3 variant moderately
      altered the catalytic efficiency of FMO3 (decrease of 30%, 60% and 6% with
      methimazole, trimethylamine and 10-(N,N-dimethylaminopentyl)-2
      (trifluoromethyl)phenothiazine, respectively). The Pro360-FMO3 variant was more
      catalytically efficient than wild-type FMO3. Pro360-FMO3 oxygenated methimazole,
      trimethylamine and 10-(N,N-dimethylaminopentyl)-2-(trifluoromethyl)phenothiazine,
      respectively, 3-, 5- and 2-fold more efficiently than wild-type FMO3. Based on
      the functional activity of the variant FMO3 enzymes, it is likely that population
      differences exist for compounds primarily metabolized by FMO3.

PMID- 12814962
TI  - Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P
      glycoprotein.
AB  - "Reaction phenotyping" studies were performed with eletriptan (ETT) to determine
      its propensity to interact with coadministered medications. Its ability to serve
      as a substrate for human P-glycoprotein (P-gp) was also investigated since a
      central mechanism of action has been proposed for this "triptan" class of drug.
      In studies with a characterized bank of human liver microsome preparations, a
      good correlation (r2 = 0.932) was obtained between formation of N-desmethyl
      eletriptan (DETT) and CYP3A4-catalyzed testosterone 6 beta-hydroxylation. DETT
      was selected to be monitored in our studies since it represents a significant ETT
      metabolite in humans, circulating at concentrations 10 to 20% of those observed
      for parent drug. ETT was metabolized to DETT by recombinant CYP2D6 (rCYP2D6) and
      rCYP3A4, and to a lesser extent by rCYP2C9 and rCYP2C19. The metabolism of ETT to
      DETT in human liver microsomes was markedly inhibited by troleandomycin,
      erythromycin, miconazole, and an inhibitory antibody to CYP3A4, but not by
      inhibitors of other major P450 enzymes. ETT had little inhibitory effect on any
      of the P450 enzymes investigated. ETT was determined to be a good substrate for
      human P-gp in vitro. In bidirectional transport studies across LLC-MDR1 and LLC
      Mdr1a cell monolayers, ETT had a BA/AB transport ratio in the range 9 to 11. This
      finding had significance in vivo since brain exposure to ETT was reduced 40-fold
      in Mdr1a+/+ relative to Mdr1a-/- mice. ETT metabolism to DETT is therefore
      catalyzed primarily by CYP3A4, and plasma concentrations are expected to be
      increased when coadministered with inhibitors of CYP3A4 and P-gp activity.

PMID- 12814963
TI  - CYP3A induction by N-hydroxyformamide tumor necrosis factor-alpha converting
      enzyme/matrix metalloproteinase inhibitors use of a pregname X receptor
      activation assay and primary hepatocyte culture for assessing induction potential
      in humans.
AB  - A series of N-hydroxyformamide tumor necrosis factor-alpha converting enzyme
      (TACE)/matrix metalloprotease (MMP) inhibitors were evaluated for their potential
      to induce human cytochrome P450 3A (CYP3A). Two in vitro assays were used: 1) a
      cell-based reporter gene assay for activation of the pregnane X receptor (PXR),
      and 2) a primary "sandwich" culture of human hepatocytes. Approximately 50
      TACE/MMP inhibitors were evaluated in the human PXR assay. A range of PXR
      activation was observed, 0 to 150% of the activation of the known human CYP3A
      inducer rifampicin. Three TACE/MMP inhibitors were evaluated in rat and human
      hepatocytes. Significantly higher PXR activation/CYP3A induction was observed in
      PXR/hepatocyte models, respectively, for (2R,3S) 3-(formyl-hydroxyamino)-2-(2
      methyl-1-propyl)-4-methylpentanoic acid [(1S,2S)-2-methyl-1-(2-pyridylcarbamoyl)
      1-butyl]amide (GW3333) compared with (2R,3S)-6,6,6-trifluoro-3
      [formyl(hydroxy)amino]-2-isobutyl-N-[(1S,2R)-2-methoxy-1-[(1,3-thiazol-2
      ylamino)carbonyl]propyl]hexanamide (GW6495) and (2R)-N-[(1S)-2,2-dimethyl-1
      [(methylamino)carbonyl]-propyl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5
      phenylpentanamide (GI4023). The CYP3A induction level achieved with GW3333 at a
      concentration of approximately 10 microM in human hepatocytes was comparable to
      that achieved with rifampicin at a concentration of 10 microM. The extent of
      rodent CYP3A induction caused by GW3333 was confirmed in vivo after daily oral
      administration for 14 days to rats. In conclusion, GW3333 is a potential inducer
      of CYP3A expression in vivo in humans, but other N-hydroxyformamides are less
      likely to induce CYP3A.

PMID- 12814964
TI  - In vitro metabolism of clindamycin in human liver and intestinal microsomes.
AB  - Incubations with human liver and gut microsomes revealed that the antibiotic,
      clindamycin, is primarily oxidized to form clindamycin sulfoxide. In this report,
      evidence is presented that the S-oxidation of clindamycin is primarily mediated
      by CYP3A. This conclusion is based upon several lines of in vitro evidence,
      including the following. 1) Incubations with clindamycin in hepatic microsomes
      from a panel of human donors showed that clindamycin sulfoxide formation
      correlated with CYP3A-catalyzed testosterone 6beta-hydroxylase activity; 2)
      coincubation with ketaconazole, a CYP3A4-specific inhibitor, markedly inhibited
      clindamycin S-oxidase activity; and 3) when clindamycin was incubated across a
      battery of recombinant heterologously expressed human cytochrome P450 (P450)
      enzymes, CYP3A4 possessed the highest clindamycin S-oxidase activity. A potential
      role for flavin-containing monooxygenases (FMOs) in clindamycin S-oxidation in
      human liver was also evaluated. Formation of clindamycin sulfoxide in human liver
      microsomes was unaffected either by heat pretreatment or by chemical inhibition
      (e.g., methimazole). Furthermore, incubations with recombinant FMO isoforms
      revealed no detectable activity toward the formation of clindamycin sulfoxide.
      Beyond identifying the drug-metabolizing enzyme responsible for clindamycin S
      oxidation, the ability of clindamycin to inhibit six human P450 enzymes was also
      evaluated. Of the P450 enzymes examined, only the activity of CYP3A4 was
      inhibited (approximately 26%) by coincubation with clindamycin (100 microM).
      Thus, it is concluded that CYP3A4 appears to account for the largest proportion
      of the observed P450 catalytic clindamycin S-oxidase activity in vitro, and this
      activity may be extrapolated to the in vivo condition.

PMID- 12814965
TI  - Verapamil: metabolism in cultures of primary human coronary arterial endothelial
      cells.
AB  - Endothelium is a metabolically active secretory tissue and an important barrier
      for metabolic products. Little is known about its contribution to drug oxidation.
      We investigated the gene and protein expression and enzyme activity of major
      cytochrome P450 monooxygenases in cultures of primary human coronary endothelial
      cells and studied its ability to metabolize verapamil, a commonly and widely
      prescribed calcium antagonist. Of the total 18 P450 monooxygenases investigated,
      transcripts for CYP1A1, CYP2A6/7, CYP2A13, CYP2B6/7, CYP2C8, CYP2E1, and CYP2J2
      were expressed, albeit at different levels. Furthermore, metabolism of verapamil
      proceeded predominantly via N-desmethylation and/or N-desalkylation, i.e.,
      production of D-617 [2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile], D
      620 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile], and
      norverapamil; but additional metabolites are the O-demethylated products, D-702
      [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-isopropyl-6
      azaoctanitrile] and D-703 [O-demethylverapamil; 5-N-(3,4
      dimethoxyphenethyl)methylamino-2-(3'-methoxy-4'-hydroxyphenyl)-2
      isopropylvaleronitrile]. We show endothelium to express an array of
      monooxygenases, and in view of its large body distribution, endothelium should be
      considered in the biotransformation of drugs, particularly when tissue-specific
      metabolism and/or metabolic inactivation are being investigated.

PMID- 12814966
TI  - Comparative disposition of (R)-(+)-pulegone in B6C3F1 mice and F344 rats.
AB  - Pulegone is a monoterpene ketone that is usually associated with the herb
      pennyroyal but is also found in the essential oils from many other mint species.
      It is the major constituent of pennyroyal oil. Pennyroyal is used as a flavoring
      and fragrance and as an herbal medicine to induce menstruation and abortion. A
      disposition study of 14C-pulegone in B6C3F1 mice and F344 rats has been conducted
      at doses from 0.8 to 80 mg/kg. Mice excrete 85 to 100% of the dose in 24 h. Rats
      excrete only 59 to 81% of the administered radioactivity in the same time,
      primarily in urine and feces, with a trace in respired air. Consequently, tissue
      concentrations are lower in mice than in rats. Male rats tend to have higher
      tissue concentrations, especially in kidney, than female rats have, but this sex
      difference is not seen in mice. The residual radioactivity at 24 h demonstrates
      potential for accumulation of pulegone-derived material in several tissues
      following multiple doses. The metabolic profile is complex in both species, with
      at least three pathways involving hydroxylation, reduction, or conjugation with
      glutathione as first steps. Mercapturic acid pathway metabolites were detected in
      bile in mice and both bile and urine in rats.

PMID- 12814967
TI  - Decabromodiphenyl ether in the rat: absorption, distribution, metabolism, and
      excretion.
AB  - Among the group of polybrominated diphenyl ethers used as flame-retardants, the
      fully brominated diphenyl ether, decabromodiphenyl ether (decaBDE), is the most
      commonly used. Despite the large usage of decaBDE, neither the metabolic pathways
      nor the absorption have been addressed, and there are very few studies on its
      toxicology. In this work, it is shown that after a single oral dose of 14C
      labeled decaBDE to rats, at least 10% of the decaBDE dose is absorbed. The major
      excretion route in conventional rats is via feces that contained 90% of the
      decaBDE dose. The excretion in bile was close to 10% of the dose and represented
      mainly metabolites. It cannot be excluded that greater than 10% of the oral dose
      had been absorbed since 65% of the radioactivity excreted in feces was
      metabolites. The highest concentrations on a lipid weight basis were found in
      plasma and blood-rich tissues, and the adipose tissue had the lowest
      concentration of decaBDE. After derivatization of a phenolic fraction, gas
      chromatography-mass spectrometry (GC/MS) analyses indicated that metabolites with
      five to seven bromine atoms had formed, and they possessed a guaiacol structure
      (a hydroxy and a methoxy group) in one of the rings. In addition, traces of
      nonabrominated diphenyl ethers and monohydroxylated metabolites were found by
      GC/MS. Metabolites, characterized by their chemical properties, were interpreted
      to be covalently bound to macromolecules, either proteins or lipids. In addition,
      water solubility was suggested. The metabolic pathway was indicated to include a
      reactive intermediate.

PMID- 12814968
TI  - Nuclear receptor, pregname X receptor, is required for induction of UDP
      glucuronosyltranferases in mouse liver by pregnenolone-16 alpha-carbonitrile.
AB  - The aim of this study was to determine the role of pregnane X receptor (PXR) in
      the induction of UDP-glucuronosyltransferases (UGTs) by pregnenolone-16 alpha
      carbonitrile (PCN). Four- to six-month-old male wild-type and PXR-null mice
      received control or PCN-treated (1500 ppm) diet for 21 days. On day 22, livers
      were taken to prepare microsomes and total RNA to determine UGT activity and mRNA
      levels, respectively. In wild-type mice, PCN treatment significantly increased
      UGT activities toward bilirubin, 1-naphthol, chloramphenicol, thyroxine, and
      triiodothyronine. On control diet, the UGT activities toward the above substrates
      (except for 1-naphthol) in the PXR-null mice were significantly higher than those
      of wild-type mice. However, UGT activities in PXR-null mice were not increased by
      PCN. In agreement with the above findings, mRNA levels of mouse Ugt1a1 and
      Ugt1a9, which are involved in the glucuronidation of bilirubin and phenolic
      compounds, were increased about 100% in wild-type mice following PCN treatment,
      whereas the expression of Ugt1a2, 1a6, and 2b5 was not affected. In contrast, PCN
      treatment had no effect on the mRNA levels of these UGTs in PXR-null mice. Taken
      together, these results indicate that PCN treatment induces glucuronidation in
      mouse liver, and that PXR regulates constitutive and PCN-inducible expression of
      some UGTs.

PMID- 12814969
TI  - Kinetic study on the reaction of cisplatin with metallothionein.
AB  - The binding of cisplatin to metallothionein (MT) was investigated at 37 degrees C
      in 10 mM Tris-NO3 (pH approximately 7.4) and 4.62 mM NaCl. The conditions were
      chosen to mimic passage of clinical concentrations of cisplatin through the
      cytosol. The reactions were monitored by high-performance liquid chromatography
      (HPLC), atomic absorption spectroscopy, and ultraviolet (UV) absorption
      spectroscopy. The UV data showed that several reactions occur, the first of which
      does not affect the absorbance (no Pt-sulfur bond formation). They also suggested
      that if [cisplatin] is large compared with [MT], the rate of subsequent reaction
      is between first and second order in [cisplatin] and between zeroth and first
      order in [MT]. HPLC eluates with 24 < retention time (tR) < 27 min contained
      undialyzable Pt, which increased with reaction time and corresponded to Pt
      thionein product. Eluates with 3 < tR < 7 min corresponded to unbound cisplatin
      and allowed determination of second-order rate constants (k), using the second
      order rate equation. The k value for cisplatin reacting with apo-MT was
      approximately 0.14 M-1 s-1, Cd/Zn-MT approximately 0.75 M-1 s-1, Cd7-MT
      approximately 0.53 M-1 s-1, and Zn7-MT approximately 0.65 M-1 s-1. Thus,
      cisplatin displaced Cd and Zn equally well. Leukocyte MT concentration was
      approximately 1.0 mM, so that the kinetics of cisplatin binding to cellular MT is
      pseudo-first order (pseudo-first-order rate constant, approximately 0.63 x 10-3 s
      1; half-life, approximately 18 min). With [cisplatin] = 10 microM, the rate of
      cisplatin reaction with MT is approximately 6.3 micromol s-1 cm-3. We conclude
      that cellular MT can trap significant amounts of cisplatin and may efficiently
      contribute to cisplatin resistance.

PMID- 12814970
TI  - Identification of CYP1A2 as the main isoform for the phase I hydroxylated
      metabolism of genistein and a prodrug converting enzyme of methylated
      isoflavones.
AB  - This study determined the cytochrome P450 (P450) isoforms responsible for
      metabolism of isoflavones using human liver microsomes (HLM) and expressed P450s.
      The primary metabolite of genistein is 3'-OH-genistein, as identified with an
      authentic chemically synthesized standard. CYP1A2 was predominantly responsible
      for 3'-OH-genistein formation since its formation was inhibited (>50%, p < 0.05)
      by a monoclonal antibody specific for CYP1A2, was correlated with CYP1A2
      activities of HLM, and was catalyzed by expressed CYP1A2. In addition to CYP1A2,
      CYP2E1 also catalyzed, although to a lesser extent, its formation. The
      contribution of these P450s to the formation of 3'-OH-genistein was also
      confirmed with a panel of expressed enzymes. Methylated isoflavones biochanin A,
      prunetin, and formononetin (10-100 microM) were rapidly converted by HLM and
      expressed CYP1A2 to more active genistein and daidzein. The conversion of
      biochanin A to genistein appears to be mainly mediated by CYP1A2 because of the
      strong correlation between the conversion rates and CYP1A2 activities in HLM.
      Thus, CYP1A2 is an effective prodrug-converting enzyme for less active methylated
      isoflavones. CYP1A2-catalyzed conversion of biochanin A to genistein (Km, 7.80
      microM; Vmax, 903 pmol/min/mg of protein; Vmax/Km, 116 microl/min/mg of protein)
      was much faster than 3'-hydroxylation of genistein (Km, 12.7 microM and Vmax, 109
      pmol/min/mg of protein; Vmax/Km, 8.6 microl/min/mg of protein). The interaction
      studies showed that genistein inhibited formation of acetaminophen from
      phenacetin with an IC50 value of 16 microM. Additional studies showed that
      phenacetin and genistein were mutually inhibitory. In conclusion, CYP1A2 and
      CYP2E1 metabolized genistein and CYP1A2 acted as prodrug-converting enzymes for
      other less active methylated isoflavones.

PMID- 12814971
TI  - Metabolism-based inactivation of neuronal nitric-oxide synthase by components of
      cigarette and cigarette smoke.
AB  - It has been shown that administration of cigarette smoke to rats leads to loss of
      neuronal nitric-oxide synthase (nNOS) activity and nNOS protein in penile tissue.
      The exact mechanism for this loss of activity and protein is not known. In the
      current study, we investigated whether extracts prepared from cigarette smoke or
      from the cigarette itself could directly inhibit nNOS activity. We discovered
      that the cigarette smoke extract and the cigarette extract cause a time-,
      concentration-, and calmodulin-dependent inactivation of nNOS in an in vitro
      system containing the purified enzyme. L-Arginine, but not D-arginine, protects
      nNOS from this time-dependent inactivation, suggesting an active site directed
      event. The kinetics of inactivation are consistent with the metabolism-based or
      suicide inactivation of nNOS. Based on studies with other metabolism-based
      inactivators, this cigarette-mediated inactivation may render nNOS more
      susceptible to proteasomal degradation and thereby may explain the loss of nNOS
      protein in vivo. The component(s) responsible for nNOS inactivation is not
      volatile, is not retained by a 3,000 molecular weight cut-off membrane, binds to
      activated charcoal, and is highly water-soluble under both acidic and basic
      conditions. The discovery of a direct inactivation of nNOS by an organic,
      cationic compound(s) present in tobacco and tobacco smoke provides a basis for
      further study of not only the mechanisms responsible for the biological effects
      of tobacco but also a search for a potentially novel inactivator of nNOS.

PMID- 12814972
TI  - In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by
      human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and
      cyp3a5.
AB  - Midazolam, triazolam (TRZ), testosterone, and nifedipine have all been widely
      used as probes for in vitro metabolism of CYP3A. We used these four substrates to
      assess the contributions of CYP3A4 and CYP3A5 to in vitro biotransformation in
      human liver microsomes (HLMs) and in recombinant enzymes. Recombinant CYP3A4 and
      CYP3A5 (rCYP3A4 and rCYP3A5) both produced 1-OH and 4-OH metabolites from
      midazolam and triazolam, 6 beta-hydroxytestosterone from testosterone, and
      oxidized nifedipine from nifedipine. Overall, the metabolic activity of CYP3A5
      was less than that of CYP3A4. Ketoconazole potently inhibited midazolam,
      triazolam, testosterone, and nifedipine metabolite formation in HLMs and in
      rCYP3A4. The inhibitory potency of ketoconazole in rCYP3A5 was about 5- to 19
      fold less than rCYP3A4 for all four substrates. In testosterone interaction
      studies, testosterone inhibited 1-OH-TRZ formation, but significantly activated 4
      OH-TRZ formation in HLMs and rCYP3A4 but not in rCYP3A5. Oxidized nifedipine
      formation was inhibited by testosterone in rCYP3A4. However, in rCYP3A5,
      testosterone slightly activated oxidized nifedipine formation at lower
      concentrations, followed by inhibition. Thus, CYP3A4 and CYP3A5 both contribute
      to midazolam, triazolam, testosterone, and nifedipine biotransformation in HLMs,
      with CYP3A5 being metabolically less active than CYP3A4 in general. Because the
      inhibitory potency of ketoconazole in rCYP3A5 is substantially less than in
      rCYP3A4 and HLMs, CYP3A5 is probably less important than CYP3A4 in drug-drug
      interactions involving ketoconazole and CYP3A substrates.

PMID- 12814973
TI  - Prediction of the in vivo interaction between midazolam and macrolides based on
      in vitro studies using human liver microsomes.
AB  - Clinical studies have revealed that plasma concentrations of midazolam after oral
      administration are greatly increased by coadministration of erythromycin and
      clarithromycin, whereas azithromycin has little effect on midazolam
      concentrations. Several macrolide antibiotics are known to be mechanism-based
      inhibitors of CYP3A, a cytochrome P450 isoform responsible for midazolam
      hydroxylation. The aim of the present study was to quantitatively predict in vivo
      drug interactions in humans involving macrolide antibiotics with different
      inhibitory potencies based on in vitro studies. alpha- and 4-Hydroxylation of
      midazolam by human liver microsomes were evaluated as CYP3A-mediated metabolic
      reactions, and the effect of preincubation with macrolides was examined. The
      hydroxylation of midazolam was inhibited in a time- and concentration-dependent
      manner following preincubation with macrolides in the presence of NADPH, whereas
      almost no inhibition was observed without preincubation. The kinetic parameters
      for enzyme inactivation (K'app and kinact) involved in midazolam alpha
      hydroxylation were 12.6 microM and 0.0240 min-1, respectively, for erythromycin,
      41.4 microM and 0.0423 min-1, respectively, for clarithromycin, and 623 microM
      and 0.0158 min-1, respectively, for azithromycin. Similar results were obtained
      for the 4-hydroxylation pathway. These parameters and the reported
      pharmacokinetic parameters of midazolam and macrolides were then used to simulate
      in vivo interactions based on a physiological flow model. The area under the
      concentration-time curve (AUC) of midazolam after oral administration was
      predicted to increase 2.9- or 3.0-fold following pretreatment with erythromycin
      (500 mg t.i.d. for 5 or 6 days, respectively) and 2.1- or 2.5-fold by
      clarithromycin (250 mg b.i.d. for 5 days or 500 mg b.i.d. for 7 days,
      respectively), whereas azithromycin (500 mg o.d. for 3 days) was predicted to
      have little effect on midazolam AUC. These results agreed well with the reported
      in vivo observations.

PMID- 12814974
TI  - Cytochrome P450 inhibition using recombinant proteins and mass
      spectrometry/multiple reaction monitoring technology in a cassette incubation.
AB  - Detailed cytochrome P450 (P450) inhibition profiles are now required for the
      registration of novel molecular entities. This method uses combined substrates
      (phenacetin, diclofenac, S-mephenytoin, bufuralol, and midazolam) with combined
      recombinant P450 enzymes (CYP1A2, 2C9, 2C19, 2D6, and 3A4) in an attempt to limit
      interactions with other more minor P450s and associated reductases. Kinetic
      analysis of single substrate with single P450 (sP450) yielded apparent Km values
      of 25, 2, 20, 9, and 3 microM, for CYP1A2, 2C9, 2C19, 2D6, and 3A4, respectively.
      Combined substrates with combined P450s (cP450) yielded apparent Km values of 65,
      4, 19, 7, and 2 microM. Selectivity of the substrates for each P450 isoform was
      checked. Phenacetin proved to be the least selective substrate. However, the
      ratio of the various P450s was modified in the final assay such that metabolism
      of phenacetin by other enzymes was approximately 20% of the metabolism by CYP1A2.
      IC50 determinations with alpha-naphthoflavone (0.04 microM), sulfaphenazole (0.26
      microM), tranylcypromine (9 microM), quinidine (0.02 microM), and ketoconazole
      (0.01 microM) were similar for sP450 and cP450 enzymes. The assay was further
      evaluated with 11 literature compounds and 52 in-house new chemical entities, and
      the data compared with radiometric/fluorescent values. The overall protein level
      of the assay was reduced from the original starting point, as this led to some
      artificially high IC50 measurements when compared with existing lower protein
      assays (radiometric/fluorometric). This method offers high throughput P450
      inhibition profiling with potential advantages over current radiometric or
      fluorometric methods.

PMID- 12814975
TI  - A new class of CYP2C9 inhibitors: probing 2C9 specificity with high-affinity
      benzbromarone derivatives.
AB  - Noncovalent forces, other than hydrophobic interactions, are important
      determinants of substrate bias exhibited by some cytochromes P450. The CYP2C9
      pharmacophore is proposed to include either an anionic group or hydrogen bond
      donor in addition to its hydrophobic groups. By constructing analogs of
      benzbromarone, evidence supporting the existence of a 2C9 anion-binding site was
      revealed. A nonsubstituted phenol analog was determined to have a pKa of 8.4 and
      a Ki of 414 nM whereas those with dihalogenated benzoyl phenols had pKa values
      between 4.2 to 5.2 and Ki values as low as 1 nM. The nonhalogenated, nonionizable
      analog is the poorest binder at 796 nM. The Ki range covers around three orders
      of magnitude with even the weakest binder being a more potent inhibitor than 2C9
      substrate phenytoin. Thus, benzbromarone derivatives represent a class of
      molecules with the potential to reveal more structural details of the 2C9 active
      site.

PMID- 12814979
TI  - The epidemiology of venous thromboembolism.
AB  - Venous thromboembolism (VTE) occurs for the first time in approximately 100
      persons per 100,000 each year in the United States, and rises exponentially from
      <5 cases per 100,000 persons <15 years old to approximately 500 cases (0.5%) per
      100,000 persons at age 80 years. Approximately one third of patients with
      symptomatic VTE manifest pulmonary embolism (PE), whereas two thirds manifest
      deep vein thrombosis (DVT) alone. Despite anticoagulant therapy, VTE recurs
      frequently in the first few months after the initial event, with a recurrence
      rate of approximately 7% at 6 months. Death occurs in approximately 6% of DVT
      cases and 12% of PE cases within 1 month of diagnosis. The time of year may
      affect the occurrence of VTE, with a higher incidence in the winter than in the
      summer. One major risk factor for VTE is ethnicity, with a significantly higher
      incidence among Caucasians and African Americans than among Hispanic persons and
      Asian-Pacific Islanders. Overall, approximately 25% to 50% of patient with first
      time VTE have an idiopathic condition, without a readily identifiable risk
      factor. Early mortality after VTE is strongly associated with presentation as PE,
      advanced age, cancer, and underlying cardiovascular disease.

PMID- 12814980
TI  - Risk factors for venous thromboembolism.
AB  - Until the 1990s, venous thromboembolism (VTE) was viewed primarily as a
      complication of hospitalization for major surgery (or associated with the late
      stage of terminal illness). However, recent trials in patients hospitalized with
      a wide variety of acute medical illnesses have demonstrated a risk of VTE in
      medical patients comparable with that seen after major general surgery. In
      addition, epidemiologic studies have shown that between one quarter and one half
      of all clinically recognized symptomatic VTEs occur in individuals who are
      neither hospitalized nor recovering from a major illness. This expanding
      understanding of the population at risk challenges physicians to carefully
      examine risk factors for VTE to identify high-risk patients who could benefit
      from prophylaxis. Factors sufficient by themselves to prompt physicians to
      consider VTE prophylaxis include major surgery, multiple trauma, hip fracture, or
      lower extremity paralysis because of spinal cord injury. Additional risk factors,
      such as previous VTE, increasing age, cardiac or respiratory failure, prolonged
      immobility, presence of central venous lines, estrogens, and a wide variety of
      inherited and acquired hematological conditions contribute to an increased risk
      for VTE. These predisposing factors are seldom sufficient by themselves to
      justify the use of prophylaxis. Nevertheless, individual risk factors, or
      combinations thereof, can have important implications for the type and duration
      of appropriate prophylaxis and should be carefully reviewed to assess the overall
      risk of VTE in each patient.

PMID- 12814981
TI  - Venous thromboembolism and cancer: risks and outcomes.
AB  - Cancer and its treatments are well-recognized risk factors for venous
      thromboembolism (VTE). Evidence suggests that the absolute risk depends on the
      tumor type, the stage or extent of the cancer, and treatment with antineoplastic
      agents. Furthermore, age, surgery, immobilization, and other comorbid features
      will also influence the overall likelihood of thrombotic complications, as they
      do in patients without cancer. The role of hereditary thrombophilia in patients
      with cancer and thrombosis is still unclear, and screening for this condition in
      cancer patients is not indicated. The most common malignancies associated with
      thrombosis are those of the breast, colon, and lung, reflecting the prevalence of
      these malignancies in the general population. When adjusted for disease
      prevalence, the cancers most strongly associated with thrombotic complications
      are those of the pancreas, ovary, and brain. Idiopathic thrombosis can be the
      first manifestation of an occult malignancy. However, intensive screening for
      cancer in patients with VTE often does not improve survival and is not generally
      warranted. Independently of the timing of cancer diagnosis (before or after the
      VTE), the life expectancy of cancer patients with VTE is relatively short,
      because of both deaths from recurrent VTE and the cancer itself. Patients with
      cancer and acute VTE who take anticoagulants for an extended period are at
      increased risk of recurrent VTE and bleeding. A recent randomized trial, the
      Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant
      Therapy for Long-Term Anticoagulation in Cancer Patients with Venous
      Thromboembolism (CLOT) study, showed that low molecular weight heparin may be a
      better treatment option for this group of patients. The antineoplastic effects of
      anticoagulants are being actively investigated with promising preliminary
      results.

PMID- 12814982
TI  - Natural history of venous thromboembolism.
AB  - Most deep vein thromboses (DVTs) start in the calf, and most probably resolve
      spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms
      or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend
      to involve the proximal veins and subsequently cause PE increases with the
      severity of the initiating prothrombotic stimulus. Although acute venous
      thromboembolism (VTE) usually presents with either leg or pulmonary symptoms,
      most patients have thrombosis at both sites at the time of diagnosis. Proximal
      DVTs resolve slowly during treatment with anticoagulants, and thrombi remain
      detectable in half of the patients after a year. Resolution of DVT is less likely
      in patients with a large initial thrombus or cancer. About 10% of patients with
      symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and
      recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly
      fatal, and an additional 5% cause death later, despite diagnosis and treatment.
      About 50% of diagnosed PEs are associated with right ventricular dysfunction,
      which is associated with a approximately 5-fold greater in-hospital mortality.
      There is approximately 50% resolution of PE after 1 month of treatment, and
      perfusion eventually returns to normal in two thirds of patients. About 5% of
      treated patients with PE develop pulmonary hypertension as a result of poor
      resolution. After a course of treatment, the risk of recurrent thrombosis is
      higher (ie, approximately 10% per patient-year) in patients without reversible
      risk factors, in those with cancer, and in those with prothrombotic biochemical
      abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.

PMID- 12814983
TI  - Primary prevention of sudden death as a novel treatment strategy in hypertrophic
      cardiomyopathy.

PMID- 12814984
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a
      multidisciplinary study: design and protocol.

PMID- 12814985
TI  - American College of Cardiology/American Heart Association clinical practice
      guidelines: Part I: where do they come from?

PMID- 12814986
TI  - Images in cardiovascular medicine. Malignant vasovagal syncope.

PMID- 12814987
TI  - Images in cardiovascular medicine. Visualization of anomalous coronary artery in
      the presence of arrhythmia using radial balanced fast field echo coronary
      magnetic resonance angiography.

PMID- 12814988
TI  - Intracoronary beta-blocker before percutaneous intervention protects myocardium.

PMID- 12814989
TI  - Proceedings of the 99th meeting of the Food and Drug Administration
      Cardiovascular and Renal Drugs Advisory Committee. May 29th and 30th, 2003.

PMID- 12814990
TI  - A comparison between real-time polymerase chain reaction and hybrid capture 2 for
      human papillomavirus DNA quantitation.
AB  - Studies investigating human papillomavirus (HPV) viral load as a risk factor in
      the development of squamous intraepithelial lesions (SILs) and cancer have often
      yielded conflicting results. These studies used a variety of HPV viral
      quantitation assays [including the commercially available hybrid capture 2 (HC 2)
      assay], which differ in their ability to account for differences in cervical cell
      collection, linear dynamic range of viral load quantitation, and determination of
      type-specific versus cumulative viral load measures. HPV-16 and HPV-18 viral
      quantitation using real-time PCR assays were performed to determine whether type
      specific viral load measurements that adjust for specimen cellularity result in a
      different association between viral load and prevalent SIL and cancer, compared
      with HC 2 quantitation (which does not adjust for cellularity or multiple
      infections). In general, HPV-16 viral load as measured by real-time PCR increased
      linearly with increasing grade of SIL while HPV-18 measured using similar
      techniques increased through low-grade SIL (LSIL), with HPV-18 viral load among
      high-grade SIL and cancers near the level of cytologically normal women. HC 2
      viral load, using the clinical 1.0 pg/ml cut point, differentiated cytologically
      normal women from women with any level of cytological abnormality (normal versus
      >/=LSIL) but did not change as lesion severity increased. There was no evidence
      for plateau of HC 2 at high copy numbers, nor was significant variability in
      total specimen cellularity observed. However, cumulative viral load measurements
      by HC 2, in the presence of multiple coinfections, overestimated type-specific
      viral load. Multiple infections were more common among women with no (32%) or
      LSIL (51%) [versus 23% in high-grade SIL/cancer], partially explaining the lack
      of a dose response using a cumulative HC2 viral load measure. The nonrandom
      distribution of multiple infections by case-control status and the apparent
      differential effect of viral load by genotype warrant caution when using HC 2
      measurements to infer viral load associations with SIL and cancer.

PMID- 12814991
TI  - The natural history of type-specific human papillomavirus infections in female
      university students.
AB  - Little is known about the average duration of type-specific human papillomavirus
      (HPV) infections and their patterns of persistence. The objectives of this study
      were to evaluate the rate of acquisition and clearance of specific HPV types in
      young women. Female university students (n = 621) in Montreal were followed for
      24 months at 6-month intervals. At each visit, a cervical specimen was collected.
      HPV DNA was detected using the MY09/MY11 PCR protocol followed by typing for 27
      HPV genotypes by a line blot assay. The Kaplan-Meier technique was used to
      estimate the cumulative probability of acquiring or clearing a HPV infection
      considering types individually or in high-risk (HR) or low-risk (LR) groups
      defined by oncogenic potential. Incidence rates were 14.0 cases/1000 women-months
      (95% confidence interval, 11.4-16.3) and 12.4 cases/1000 women-months (95%
      confidence interval, 10.4-14.8) for acquiring HR and LR HPV infections,
      respectively. The 24-month cumulative rates of acquisition were highest for HPV
      16 (12%), HPV-51, and HPV-84 (8%). Of the incident infections, HPV-16 was the
      most persistent (mean duration, 18.3 months), followed by HPV-31 and HPV-53 (14.6
      and 14.8 months, respectively). HPV-6 and HPV-84 had the shortest mean duration
      time (<10 months) The mean durations of incident, same-type LR or HR HPV
      infections were 13.4 months and 16.3 months, respectively. Whereas the majority
      of episodes with a type-specific HPV infection cleared within 2 years, there were
      many women who were either reinfected with a new HPV genotype or presumably
      experienced reactivation of their initial infection.

PMID- 12814992
TI  - Issues in the epidemiological analysis and interpretation of intermediate
      biomarkers.
AB  - We critically reviewed the validity and interpretation of two analytical
      approaches that have been used in the molecular epidemiological literature to
      investigate the role of gene-environment (GxE) interactions in disease (D)
      causation. Several studies have attempted to use biomarkers of biologically
      effective dose (BBED) such as polycyclic aromatic hydrocarbon-DNA and alfatoxin
      albumin adducts to assess possible GxE interactions. To truly determine whether
      BBED results from a GxE interaction that is causally implicated in disease
      development would require data on G, E, BBED, and D, and thus far, few studies
      have had data on each of these components. In the absence of data on an
      antecedent E, one approach has been to assess interactions between G and BBED on
      D and to interpret the results as providing information on the presence of GxE
      interactions. In the absence of data on G, another approach has been to control
      for E in analyses of BBED and D and to interpret nonnull risk estimates for BBED
      as reflecting the role of G. We show that neither approach is valid. Analyses of
      interactions between G and BBED cannot be used to draw conclusions about the
      presence or absence of GxE interactions. Similarly, analyses of BBED and D,
      controlling for E, do not provide insight into the role of G. We discuss how
      differences in the risk estimate for BBED, with and without control for E may be
      interpreted.

PMID- 12814993
TI  - Urinary phytoestrogen excretion and breast cancer risk: evaluating potential
      effect modifiers endogenous estrogens and anthropometrics.
AB  - Steroid sex hormones play a central role in breast carcinogenesis. Evidence from
      in vitro and animal studies suggests that phytoestrogens may inhibit the
      development of mammary tumors through their role in regulating the synthesis,
      metabolism, and signal transduction of steroid hormones. In a study of 117 case
      control pairs of postmenopausal women in Shanghai, we investigated whether the
      association between urinary phytoestrogen excretion and breast cancer risk may
      differ by levels of endogenous steroid sex hormones, sex hormone binding globulin
      (SHBG), body mass index (BMI), and waist:hip ratio (WHR). Fasting morning blood
      and urine samples were collected for the analysis of urinary isoflavonoids and
      mammalian lignans, as well as blood levels of SHBG and selected steroid hormones.
      For cancer patients, samples were collected before any cancer therapy.
      Conditional logistic regression models were used to estimate odds ratios and 95%
      confidence intervals after adjusting for potential confounding factors. The
      inverse associations between urinary phytoestrogens and breast cancer risk were
      found to be more evident among women with a high BMI or WHR than those with a low
      level of these anthropometric measurements. Although a reduced risk of breast
      cancer was observed among women with a high excretion rate of urinary
      isoflavonoids in all of the strata defined by blood SHBG and steroid hormones,
      the inverse association was more pronounced among women with a high blood
      concentration of estradiol, a low level of estrone sulfate, or a low level of
      SHBG. The risks of breast cancer were also reduced with increasing excretion rate
      of mammalian lignans, although no test for a linear association was statistically
      significant in stratified analyses. Findings from this study suggest that the
      potential protective association of phytoestrogens may be modified by BMI, WHR,
      and blood levels of SHBG, and steroid hormones.

PMID- 12814994
TI  - Nonsmoking-related arylamine exposure and bladder cancer risk.
AB  - Roughly one-half of bladder cancer incidence in the United States can be
      attributed to known causes, mainly cigarette smoking, and it has been
      hypothesized that the aromatic amines in tobacco smoke are important etiological
      agents. Nonsmokers are also exposed, through unknown sources, to many of the same
      carcinogenic aromatic amines that are present in cigarette smoke. Previous
      epidemiological studies have not tested whether either of these aromatic amine
      exposures are associated with cancer risk. We conducted a population-based case
      control study in Los Angeles County, California, involving 761 case patients with
      bladder cancer and 770 individually matched control subjects. In-person
      interviews provided information on tobacco smoking and other potential risk
      factors. Quantitative analysis of hemoglobin adducts of 4- and 3-aminobiphenyl
      (ABP) was used to assess aromatic amine exposure. Adducts of both aminobiphenyls
      were significantly higher in cases than in controls, independent of cigarette
      smoking at the time of blood collection and lifetime smoking history. Adjustment
      for other risk factors as well as for metabolic differences did not materially
      alter the associations. Our findings strengthen the connection between exposure
      to aromatic amines in tobacco smoke and cigarette smoking-related bladder cancer
      and suggest that environmental exposure to arylamines may account for a
      significant proportion of nonsmoking-related bladder cancer in the general
      population.

PMID- 12814995
TI  - Mate consumption and the risk of squamous cell esophageal cancer in uruguay.
AB  - A retrospective hospital-based case-control study was carried out at the Oncology
      Institute of Montevideo, Uruguay, to investigate the role of mate consumption in
      esophageal cancer risk. The study included 344 cases with squamous cell carcinoma
      of the esophagus and 469 controls recruited between January 1988 and August 2000.
      Mate consumption was significantly associated with an increased risk of
      developing esophageal cancer and showed a clear dose response, with a relative
      risk of 2.84 [95% confidence interval (CI), 1.41-5.73] for those drinking more
      than 1 liter/day of mate as compared with nondrinkers. Subjects who self-reported
      drinking mate at a very hot temperature had an almost 2-fold increase in risk
      [odds ratio (OR), 1.87; 95% CI, 1.17-3.00] compared with those drinking warm to
      hot mate, after adjusting for cumulative consumption of mate. Mate amount and
      temperature were observed to have independent effects and, although no departure
      from multiplicativity was observed between the two covariates, those drinking
      more than 1 liter/day of mate at a very hot temperature had a 3-fold increase in
      risk (OR, 2.95; 95% CI, 1.30-6.74) compared with those drinking less than 0.5
      liter/day of mate at a warm to hot temperature. Subjects with high cumulative
      exposure to mate in the presence of low alcohol and tobacco exposures presented a
      lower-risk estimate (OR, 1.52; 95% CI, 0.88-2.62), whereas those with high
      cumulative exposures to mate, alcohol, and tobacco presented a 7-fold increase in
      esophageal cancer risk (OR, 7.10; 95% CI, 3.75-13.46). The population
      attributable fraction as a result of mate consumption was calculated to be 53%,
      of which the sole effect of amount and temperature was 14.8 and 12.6%
      respectively, and 14.9% was attributable to high mate consumption at high
      temperature.

PMID- 12814996
TI  - Laryngeal cancer in women: tobacco, alcohol, nutritional, and hormonal factors.
AB  - Laryngeal cancer is the neoplasm with the largest male to female sex ratio in
      most populations. Thus, inadequate data are available on women. We analyzed
      several risk factors in the combined dataset from two case-control studies
      conducted between 1986 and 2000 in northern Italy and Switzerland. Cases were 68
      women under age 79 years, with incident, histologically confirmed cancer of the
      larynx. Controls were 340 women, admitted to the same network of hospitals as
      cases, for acute, nonmalignant conditions, unrelated to tobacco and alcohol
      consumption. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      were estimated by logistic regression models, conditioned by age, study center
      and year of interview, and including terms for education, body mass index,
      tobacco, alcohol drinking, and nonalcohol energy intake. Laryngeal cancer was
      strongly associated with cigarette smoking (OR = 435.7, 95% CI: 38.2-4964.4 for
      smokers of >/=25 cigarettes/day) and alcohol drinking (OR = 4.3, 95% CI: 0.8-24.1
      for >/=5 drinks/day). An inverse relation was found for vegetables (OR = 0.3, 95%
      CI: 0.1-0.9 for the highest level of consumption), fruit (OR = 0.5, 95% CI: 0.2
      1.3), and olive oil (OR = 0.3, 95% CI: 0.1-0.9). Reproductive and hormonal
      factors were not consistently associated to laryngeal cancer risk. This
      investigation, based on a uniquely large number of laryngeal cancers in women,
      provides definite evidence that cigarette smoking is the prominent risk factor
      for laryngeal cancer in women, accounting for 78% of cases in this population.
      Alcohol and selected dietary aspects account for approximately 30% of cases,
      whereas menstrual and hormonal factors do not appear to have a consistent role in
      laryngeal carcinogenesis.

PMID- 12814997
TI  - The association between lung and prostate cancer risk, and serum micronutrients:
      results and lessons learned from beta-carotene and retinol efficacy trial.
AB  - beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial
      that recruited 18,314 high-risk individuals to test the effect of supplemental
      beta-carotene and retinol on lung cancer incidence. In this report, we conducted
      a prospective nested case-control study of the association between serum
      carotenoids, retinoids, and tocopherols on both lung and prostate cancer
      incidence. Prerandomization serum samples were selected from 278 lung cancer
      cases and 205 prostate cancer cases, and 483 controls matched by high-risk
      population, study center location, age, sex (lung cancer only), smoking status,
      and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed
      by high-performance liquid chromatography. Endpoints were confirmed by pathology
      review (lung cancer) or review of the pathology report (prostate cancer). In the
      control-only population, there was a significant association between tobacco use
      and serum micronutrient concentration. Current smokers compared with former
      smokers had lower mean levels of all of the micronutrients tested with
      zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and
      retinyl palmitate reaching statistical significance at P = 0.05. In the overall
      population, the mean serum concentrations of all of the micronutrients except
      gamma-tocopherol were lower for lung cancer cases than controls. Statistically
      significant trends across quartiles were observed in lutein (P = 0.02),
      zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings
      in the overall population were because of the strong inverse association between
      serum micronutrients and lung cancer in females. Statistically significant odds
      ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen
      in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31;
      CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate
      cancer, mean serum concentrations were lower in cases for all of the nutrients
      except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the
      findings statistically significant. There was no statistically significant
      association between serum carotenoids and prostate cancer. Our findings provide
      additional support for the association between physiological levels of dietary
      micronutrients and cancer incidence.

PMID- 12814998
TI  - Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung
      cancer patients.
AB  - Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive
      oxidants, so GST polymorphisms may influence survival after diagnosis of cancer.
      We evaluated survival according to GST polymorphisms in a population-based series
      of lung cancer patients. The study subjects (n = 274) were men diagnosed with
      lung cancer from 1993 through 1996 who participated in a case control study and
      provided a blood sample for genotyping. The presence of the GSTM1 and GSTT1 genes
      were assayed by multiplex PCR. Genotype at the GSTP1 Ile(105)Val substitution was
      determined by PCR and oligonucleotide ligation assay. The study subjects were
      followed for vital status through 2000, and overall survival was evaluated in
      Kaplan-Meier survival functions and Cox proportional hazards models. Subjects
      with the GSTM1 null genotype had shorter survival; the proportion of GSTM1 null
      subjects surviving at 5 years was 0.20 [95% confidence interval (CI) 0.14-0.27],
      compared with 0.29 (95% CI 0.22-0.37) for GSTM1 present subjects. The relative
      risk of death associated with GSTM1 null genotype, adjusted for stage at
      diagnosis and histology, was 1.36, 95% CI 1.04-1.80. There was no association
      between GSTT1 or GSTP1 genotype and survival in the overall study population, nor
      in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our
      results are consistent with a previous study, which also observed that the GSTM1
      null genotype, which confers susceptibility to lung cancer, was associated with
      shorter survival. Future studies of lung cancer survival should take into account
      GSTM1 genotype as well as investigate underlying mechanisms.

PMID- 12814999
TI  - Non-steroidal anti-inflammatory drug use and risk of adult leukemia.
AB  - Epidemiological studies have suggested that regular use of aspirin and other non
      steroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of
      some types of malignancy. Leukemia incidence and self-reported aspirin, as well
      as other NSAID use, was examined in a prospective cohort of >28,000
      postmenopausal women. Eighty-one incident leukemia cases occurred during the
      period 1993-2000. The multivariate-adjusted relative risk of leukemia was 0.45
      (95% confidence interval: 0.27-0.75) for women who reported using aspirin two or
      more times per week compared with women who reported no use. Similar inverse
      associations were observed for the two subtypes of leukemia analyzed. In
      contrast, for women who reported using nonaspirin NSAIDs, the multivariate
      adjusted relative risk of leukemia was 1.31 (95% confidence interval: 0.77-2.22).
      Analyses that excluded cases diagnosed before 1995 did not notably alter results.
      To our knowledge, this is the first prospective study to examine the association
      between NSAID use and incident adult leukemia. Although preliminary, the notable
      differences observed in leukemia risk between aspirin and nonaspirin NSAID use
      warrant further investigation.

PMID- 12815000
TI  - Cancer incidence and mortality among the parents of a population-based series of
      2604 children with cancer.
AB  - The purpose is to determine cancer incidence and mortality from all causes among
      parents of children with solid tumors and to formulate hypotheses about heritable
      risks and associations with parental environmental exposures. A total of 2604
      children ages < 15 years included in the Manchester Children's Tumor Registry,
      1954-1996, was eligible. Parents of index children were traced and followed up to
      December 31, 2000, through the United Kingdom National Health Service Central
      Register. Data on cancer diagnosis and all causes of deaths were obtained.
      Standardized incidence (SIR) and standardized mortality (SMR) ratios, Ps, and 95%
      confidence intervals were calculated from serial age and sex-specific cancer
      incidence and mortality data for England and Wales. There was a significant
      excess of cancers in parents overall (observed number = 481, expected number =
      428.9, SIR = 1.1; P < 0.05) because of central nervous system tumors (SIR = 1.7;
      P < 0.05), carcinoma breast (SIR = 1.3; P < 0.05), bone and soft tissue sarcoma
      (SIR = 2.9; P < 0.01), and retinoblastoma (SIR = 62.1; P < 0.001). Diagnoses in
      the index children associated with excess risk of cancer in their parents were
      retinoblastoma (SIR = 1.8; P < 0.01) and gonadal germ cell tumors (SIR = 2.3; P <
      0.01). There was no excess risk of death from all causes considered together
      (observed number = 791, expected number = 814.2) nor from any specific cause.
      These results indicate that there is a small excess of incident cancers among
      parents of children with solid tumors, probably mainly because of known genes,
      but mortality is similar to the general population. The study is very reassuring
      for families of children with cancer.

PMID- 12815001
TI  - Formation of DNA adducts and induction of lacI mutations in Big Blue Rat-2 cells
      treated with temozolomide: implications for the treatment of low-grade adult and
      pediatric brain tumors.
AB  - Temozolomide (TMZ) is a chemotherapeutic agent used in the treatment of high
      grade brain tumors. Treatment of patients with alkylating chemotherapeutic agents
      has been established to increase their risk for acute myelogenous leukemia. The
      formation of DNA adducts and induction of mutations are likely to play a role in
      the etiology of therapy-related acute myeloid leukemia. To evaluate this issue
      for TMZ, we have measured the formation of DNA adducts and induction of lacI
      mutations in Big Blue Rat-2 cells treated with TMZ. Treatment of Big Blue Rat-2
      cells with either 0, 0.5, or 1 mM TMZ resulted in lacI mutant frequencies of 9.1
      +/- 2.9 x 10(-5), 48.9 +/- 12 x 10(-5), and 89.7 +/- 40.3 x 10(-5), respectively.
      Comparison of the mutant frequencies demonstrated that 0.5 and 1 mM TMZ
      treatments increased the mutant frequencies by 5.3- and 9.8-fold and that this
      increase was significant (P < 0.001). Sequence analysis of the lacI mutants from
      the TMZ treatment group demonstrated that they were GC-->AT transitions at non
      CpG sites, which is significantly different from the mutation spectrum observed
      in the control treatment group. Treatment of Big Blue Rat-2 cells with various
      concentrations of TMZ produced a linear increase in the levels of N7
      methylguanine and O(6)-methylguanine. The lacI mutation spectrum induced by TMZ
      treatment is consistent with these mutations being produced by O(6)-MeG. This
      study establishes TMZ has significant mutagenic potential and suggests that
      careful consideration in the use of TMZ for the treatment of low-grade adult and
      pediatric brain tumors should be given.

PMID- 12815002
TI  - Correlates of mammogram density in southwestern Native-American women.
AB  - Little is known about the breast cancer risk factors or mammogram characteristics
      among Native-American women. Southwestern Native-American women have a low risk
      of breast cancer and a high risk of diabetes. Our purpose was to determine the
      prevalence of known clinical risk factors for breast cancer and their association
      with mammogram density in a sample of Southwestern Native-American women
      undergoing breast cancer screening. A retrospective review was performed of
      screening mammogram examinations in 455 women. Density was classified by American
      College of Radiology Breast Imaging Reporting and Data System (BIRADS) density
      patterns 1 to 4 (fat to dense). Clinical data including patient age, weight, body
      mass index, parity, lactation, age at first birth, menopause status, hormone
      replacement therapy, diabetes status, and family history of breast cancer were
      obtained. Multivariate analyses were performed. Among the entire group, 152 women
      (33.4%) had diabetes. Patient age (P = 0.0012), weight (P < 0.0001), menopause
      status (P = 0.0134), estrogen use (P = 0.0311), age at first birth (P = 0.0035),
      and diabetes (P = 0.0015) were associated with mammogram density. Diabetes was
      associated with mammogram density in premenopausal women (P = 0.0032) but not in
      postmenopausal women (P = 0.3178) in stratified analyses. Diabetes, hormone
      replacement therapy, age, weight, menopause status, parity, and age at first
      birth were significantly associated with mammogram density. The association of
      mammogram density with diabetes varied by menopause status and was significant
      only for premenopausal women.

PMID- 12815003
TI  - Vitamin C intake and apoptosis in normal rectal epithelium.
AB  - Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing
      genetically damaged or mutated cells. A high rate of apoptosis has been linked to
      a reduced risk of colorectal adenomas; therefore, it is important to understand
      factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from
      harmful oxidation processes but may interfere with apoptosis by protecting
      genetically damaged cells from reactive oxygen species-dependent cell death. The
      objective of this study was to evaluate the association between vitamin C intake
      and apoptosis in normal rectal mucosa. Study participants were part of a large,
      cross-sectional study, the Diet and Health Study III. Participants were recruited
      from consecutive, consenting patients who underwent colonoscopy at University of
      North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C
      intake, obtained from a food frequency questionnaire, included both dietary
      sources and vitamin supplements. Apoptosis was measured by morphological
      evaluation of H&E-stained sections obtained from pinch biopsy samples of normal
      rectal mucosa in consenting participants (n = 503). The relationship between
      vitamin C and apoptosis varied by adenoma status. Among individuals with
      adenomas, there was an inverse linear association between apoptosis and total
      vitamin C intake. Similarly, individuals with adenomas in the highest quintile of
      total vitamin C intake were substantially less likely than those in the lowest
      quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence
      interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis
      in adenoma-free patients. High vitamin C intake was associated with reduced
      colorectal apoptosis among individuals with adenomas in this study population.
      Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements
      may be contraindicated for patients with a history of adenomas.

PMID- 12815004
TI  - Induction of NAD(P)H quinone: oxidoreductase1 inhibits carcinogen-induced
      aberrant crypt foci in colons of Sprague-Dawley rats.
AB  - Phase II detoxifying enzymes like NAD(P)H (quinone acceptor)oxidoreductase1
      (NQO1), glutathione S-transferases (GST), and UDP-glucuronyltransferases (UGT)
      may play an important role in preventing carcinogen-induced cancers. Inducers of
      these enzymes have been shown to inhibit carcinogen-induced colon tumors in rat
      and mouse models. However, it has not been clearly demonstrated that NQO1
      contributes to this effect. We examined the effect of NQO1 inducers on colon
      carcinogenesis using an aberrant crypt foci (ACF) rat model. Sprague-Dawley rats
      were fed control diet or diet containing 400 ppm dimethyl fumarate or 200 ppm
      oltipraz for 7 days, and Phase II enzymes in rat colon and liver were measured.
      Dimethyl fumarate significantly increased NQO1 and GST activities in colon and
      liver but did not increase UGT activities in these tissues. In contrast, oltipraz
      significantly increased NQO1 activities in colon and liver and produced a small
      increase in GST activity in the liver but did not increase GST activity in the
      colon or UGT activities in the liver or colon. Sprague Dawley rats were fed
      control diet or diet containing 200 ppm oltipraz and then treated with the
      carcinogens azoxymethane or methyl nitrosourea. Both carcinogens produced ACF in
      all of the rat colons, but rats fed oltipraz diet had significantly fewer ACF
      than those fed control diet. This protective effect was reversed in rats treated
      with the NQO1 inhibitor, dicoumarol. However, treatment with oltipraz did not
      alter the distribution of crypt multiplicities in the ACF. These studies
      demonstrated that induction of NQO1 plays a significant role in inhibiting
      initiation of carcinogen-induced ACF in Sprague-Dawley rats. This provides the
      first direct evidence that NQO1 may play a role in preventing colon cancer. The
      study also found that oltipraz added to the diet of Sprague-Dawley rats
      selectively increased NQO1 activity in colon mucosa with no increase in GST and
      UGT activities in these tissues. Thus, this model will be useful for further
      investigating the role of NQO1 in prevention of colon cancer.

PMID- 12815005
TI  - Dietary glycemic index, glycemic load, and risk of incident breast cancer in
      postmenopausal women.
AB  - Insulin and insulin-like growth factor-I (IGF-I) are associated with increased
      risk of breast cancer in several studies. Circulating concentrations of insulin
      increase with dietary consumption of high glycemic index foods, which, in turn,
      may influence IGF-I levels or activity, but the relevance of such dietary
      patterns for breast cancer risk is unclear. We investigated whether consumption
      of carbohydrates with high dietary glycemic index would predict risk of
      postmenopausal breast cancer among 63,307 United States women in the Cancer
      Prevention Study II Nutrition Cohort. From baseline in 1992, participants 40-87
      years of age and free from cancer and diabetes, were followed for 5 years; 1442
      incident breast cancer cases were documented. Diet was assessed at baseline by a
      validated 68-item food frequency questionnaire from which we calculated dietary
      glycemic index and glycemic load. Dietary glycemic index and load were not
      associated with increased risk of postmenopausal breast cancer (rate ratio =
      1.03; 95% confidence interval, 0.87-1.22 and rate ratio = 0.90; 95% confidence
      interval, 0.76-1.08, respectively) after adjustment for multiple breast cancer
      risk factors. Associations were not modified by body mass index, physical
      activity, hormone use, or stage of disease. Future evaluations of glycemic index
      and breast cancer risk may be strengthened by longer follow-up, more complete
      dietary information, and measurement of plasma insulin and IGF-I levels.

PMID- 12815006
TI  - Association between two polymorphisms in the SRD5A2 gene and serum androgen
      concentrations in British men.
AB  - Androgens are essential for the growth of the prostate gland and have been
      implicated in the development of prostate cancer. Little is known about the
      determinants of androgen levels in men, although observed ethnic differences
      suggest they may have a genetic basis. Several polymorphisms have been identified
      in the steroid 5 alpha-reductase type II gene (SRD5A2), which encodes an enzyme
      that catalyzes the conversion of testosterone to its more potent metabolite,
      dihydrotestosterone. Although some of these polymorphisms have been associated
      with increased prostate cancer risk, the association with circulating androgen
      levels remains unclear. The purpose of this study is to investigate the
      association between the (TA)(n) dinucleotide repeat polymorphism in the 3'
      untranslated region and the A49T polymorphism (which replaces the normal alanine
      with threonine at codon 49) in the SRD5A2 gene and serum androgen concentrations
      in 604 British men. In particular, we wanted to test the hypotheses that the
      variant alleles are associated with an increased serum concentration of
      androstanediol glucuronide, a direct metabolite of dihydrotestosterone and a
      serum marker of 5 alpha-reductase activity. Mean hormone concentrations were
      evaluated in each genotype, and adjusted for age and other relevant factors. We
      found no evidence that the SRD5A2 (TA)(n) repeat polymorphism was associated with
      androgen levels. Men who possessed one or two copies of the variant T allele in
      the A49T polymorphism had a significantly 24% lower androstanediol glucuronide
      concentration than men who were homozygous for the wild-type allele (P = 0.0003).
      Because of the rarity of this variant allele, larger studies are needed to
      additionally clarify the role of the A49T polymorphism in androgen metabolism.

PMID- 12815007
TI  - The fibroblast growth factor receptor gene Arg388 allele is not associated with
      early lymph node metastasis of breast cancer.

PMID- 12815008
TI  - No association between the DNA repair gene XRCC3 T241M polymorphism and risk of
      skin cancer and breast cancer.

PMID- 12815010
TI  - Correspondence re: Schoen et al., Lack of association between adipose tissue
      distribution, and insulin-like growth factor-I and insulin-like growth factor
      binding protein-3 in men and women. Cancer Epidemiol. Biomark. Prev., 11: 581
      586, 2002.

PMID- 12815011
TI  - Evidence that nuclear factor-kappa B activation is critical in oxidant-induced
      disruption of the microtubule cytoskeleton and barrier integrity and that its
      inactivation is essential in epidermal growth factor-mediated protection of the
      monolayers of intestinal epithelia.
AB  - Using monolayers of intestinal (Caco-2) cells, we showed that oxidants disrupt
      the microtubule cytoskeleton and barrier integrity; epidermal growth factor (EGF)
      was protective via stabilization of the microtubules. Because proinflammatory
      conditions activate nuclear factor-kappaB (NF-kappaB), we hypothesized that
      oxidants disrupt barrier integrity through activation of NF-kappaB and that EGF
      protects by suppressing NF-kappaB. Parental cells were pretreated with EGF or NF
      kappaB or inhibitory kappaBalpha (I-kappaBalpha) modulators. Other cells were
      stably transfected with varying levels of a dominant negative mutant for the NF
      kappaB inhibitor I-kappaBalpha. Both types of cells were grown as monolayers and
      then exposed to oxidant (H2O2). We then monitored monolayer barrier integrity
      (permeability), stability of the microtubule cytoskeleton (confocal microscopy,
      immunoblotting), intracellular levels of the I-kappaBalpha (immunoblotting),
      translocation, and activity of NF-kappaB (immunoblotting, sensitive enzyme-linked
      immunosorbent assay). Monolayers were also fractionated and processed to assess
      alterations in 1) polymerized tubulin (S2; an index of cytoskeletal integrity)
      and 2) monomeric tubulin (S1; an index of disassembly) (polyacrylamide gel
      electrophoresis fractionation and immunoblotting). We found the following: 1)
      Oxidants caused I-kappaBalpha degradation, NF-kappaB translocation, NF-kappaB
      (p50 and p65 subunits) activation, tubulin disassembly ( upward arrow S1,
      downward arrow S2), microtubule architectural instability, and barrier
      disruption. I-kappaBalpha stabilizers and NF-kappaB inhibitors [e.g.,
      carbobenzyloxy-leuleu-leucinol (MG-132), lactacystin] suppressed oxidants
      injurious effects. 2) EGF (10 ng/ml) stabilized I-kappaBalpha and prevented both
      NF-kappaB translocation and activation while protecting monolayers against
      oxidants. 3) In stably transfected cells, transfection-induced stabilization of I
      kappaBalpha by itself led to EGF-like protective effects. In these mutant cells,
      protection was not potentiated by EGF (10 ng/ml). Conclusions are 1) oxidants
      induce disruption of the cytoskeleton and intestinal barrier integrity, in part,
      through I-kappaBalpha degradation and subsequent NF-kappaB activation, 2) I
      kappaBalpha stabilization is by itself protective, mimicking EGF, and 3) EGF
      protects cell monolayers through I-kappaBalpha stabilization and NF-kappaB
      inactivation. To our knowledge, this is the first report that NF-kappaB can
      affect the dynamics of cytoskeletal assembly and intestinal barrier integrity.

PMID- 12815012
TI  - Glucagon-like peptide-2 and common therapeutics in a murine model of ulcerative
      colitis.
AB  - The intestinal hormone glucagon-like peptide-2 (GLP-2) enhances bowel growth and
      reduces the severity of colonic injury in dextran sulfate sodium (DSS)-induced
      colitis in mice. In humans, ulcerative colitis is normally treated with
      aminosalicylates (ASAs) and corticosteroids (CSs) to reduce inflammation.
      However, whether the intestinotropic effects of GLP-2 are altered when combined
      with ASAs and/or CSs has not previously been explored. Thus, each agent [vehicle,
      ASA (sulfasalazine), CS (methylprednisolone), and ASA + CS] was administered
      alone or with GLP-2 to normal mice or mice with 3.5% DSS in the drinking water,
      for 10 consecutive days. GLP-2 treatment of DSS-mice increased survival and small
      intestinal weight (p < 0.05), and decreased body weight loss and colonic damage
      (p < 0.05). Furthermore, GLP-2 increased the number of proliferating cells in the
      colonic crypts of DSS-mice (p < 0.05). Administration of ASA, CS, or ASA + CS
      alone did not affect growth of the intestine in DSS-mice. However, administration
      of GLP-2 in combination with ASA was permissive for the beneficial effects of GLP
      2 on survival and colonic damage, whereas CS treatment prevented these effects of
      GLP-2. Concomitant administration of GLP-2 with ASA + CS resulted in intermediate
      effects. No differences between colonic myeloperoxidase activity or IkappaB
      levels (an inhibitor of the nuclear factor-kappaB pro-inflammatory pathway) were
      found for any of these therapeutic agents. When taken together, the ability of
      GLP-2 to protect colonic mucosal architecture in DSS-colitis, and its
      effectiveness when given in combination with ASA, but not with CS, suggests a
      novel approach for the treatment of patients with colitis.

PMID- 12815013
TI  - Watermaze learning enhances excitability of CA1 pyramidal neurons.
AB  - The dorsal hippocampus is crucial for learning the hidden-platform location in
      the hippocampus-dependent, spatial watermaze task. We have previously
      demonstrated that the postburst afterhyperpolarization (AHP) of hippocampal
      pyramidal neurons is reduced after acquisition of the hippocampus-dependent,
      temporal trace eyeblink conditioning task. We report here that the AHP and one or
      more of its associated currents (IAHP and/or sIAHP) are reduced in dorsal
      hippocampal CA1 pyramidal neurons from rats that learned the watermaze task as
      compared with neurons from control rats. This reduction was a learning-induced
      phenomenon as the AHP of CA1 neurons from rats that failed to learn the hidden
      platform location was similar to that of neurons from control rats. We propose
      that reduction of the AHP in pyramidal neurons in regions crucial for learning is
      a cellular mechanism of learning that is conserved across species and tasks.

PMID- 12815014
TI  - mGluR1, but not mGluR5, mediates depolarization of spinal cord neurons by
      blocking a leak current.
AB  - The modulation of neuronal excitability by group I metabotropic glutamate
      receptors (mGluRs) was studied in isolated lamprey spinal cord. At resting
      potential, application of the group I mGluR agonist (R,S)-3,5
      dihydroxyphenylglycine (DHPG) slightly depolarized the cells. However, at
      depolarized membrane potentials, this agonist induced repetitive firing. When Na+
      channels were blocked by TTX, DHPG induced a slight depolarization at rest that
      increased in amplitude as the neurons were held at more depolarized membrane
      potentials. In voltage-clamp conditions, DHPG application induced an inward
      current associated with a decrease in membrane conductance when cells were held
      at -40 mV. At resting membrane potential, no significant change in the current
      was induced by DHPG, although a decrease in membrane conductance was seen. The
      conductance blocked by DHPG corresponded to a leak current, since DHPG had no
      effect on the voltage-gated current elicited by a voltage step from -60 to -40
      mV, when leak currents were subtracted. The leak current blocked by DHPG is
      mediated by fluxes of both K+ and Na+. The subtype of group I mGluR mediating the
      block of the leak current was characterized using specific antagonists for mGluR1
      and mGluR5. The inhibition of the leak current was blocked by the mGluR1
      antagonist LY 367385 but not by the mGluR5 antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP). The DHPG-induced blockage of the leak current
      required phospholipase C (PLC)-activation and release of Ca2+ from internal
      stores as the effect of DHPG was suppressed by the PLC-blocker U-73122 and after
      depletion of intracellular Ca2+ pools by thapsigargin. Our results thus show that
      mGluR1 activation depolarizes spinal neurons by inhibiting a leak current. This
      will boost membrane depolarization and result in an increase in the excitability
      of spinal cord neurons, which could contribute to the modulation of the activity
      of the spinal locomotor network.

PMID- 12815015
TI  - Evidence for object permanence in the smooth-pursuit eye movements of monkeys.
AB  - We recorded the smooth-pursuit eye movements of monkeys in response to targets
      that were extinguished (blinked) for 200 ms in mid-trajectory. Eye velocity
      declined considerably during the target blinks, even when the blinks were
      completely predictable in time and space. Eye velocity declined whether blinks
      were presented during steady-state pursuit of a constant-velocity target, during
      initiation of pursuit before target velocity was reached, or during eye
      accelerations induced by a change in target velocity. When a physical occluder
      covered the trajectory of the target during blinks, creating the impression that
      the target moved behind it, the decline in eye velocity was reduced or abolished.
      If the target was occluded once the eye had reached target velocity, pursuit was
      only slightly poorer than normal, uninterrupted pursuit. In contrast, if the
      target was occluded during the initiation of pursuit, while the eye was
      accelerating toward target velocity, pursuit during occlusion was very different
      from normal pursuit. Eye velocity remained relatively stable during target
      occlusion, showing much less acceleration than normal pursuit and much less of a
      decline than was produced by a target blink. Anticipatory or predictive eye
      acceleration was typically observed just prior to the reappearance of the target.
      Computer simulations show that these results are best understood by assuming that
      a mechanism of eye-velocity memory remains engaged during target occlusion but is
      disengaged during target blinks.

PMID- 12815016
TI  - Spectrotemporal structure of receptive fields in areas AI and AAF of mouse
      auditory cortex.
AB  - The mouse is a promising model system for auditory cortex research because of the
      powerful genetic tools available for manipulating its neural circuitry. Previous
      studies have identified two tonotopic auditory areas in the mouse-primary
      auditory cortex (AI) and anterior auditory field (AAF)- but auditory receptive
      fields in these areas have not yet been described. To establish a foundation for
      investigating auditory cortical circuitry and plasticity in the mouse, we
      characterized receptive-field structure in AI and AAF of anesthetized mice using
      spectrally complex and temporally dynamic stimuli as well as simple tonal
      stimuli. Spectrotemporal receptive fields (STRFs) were derived from
      extracellularly recorded responses to complex stimuli, and frequency-intensity
      tuning curves were constructed from responses to simple tonal stimuli. Both
      analyses revealed temporal differences between AI and AAF responses: peak
      latencies and receptive-field durations for STRFs and first-spike latencies for
      responses to tone bursts were significantly longer in AI than in AAF. Spectral
      properties of AI and AAF receptive fields were more similar, although STRF
      bandwidths were slightly broader in AI than in AAF. Finally, in both AI and AAF,
      a substantial minority of STRFs were spectrotemporally inseparable. The
      spectrotemporal interaction typically appeared in the form of clearly disjoint
      excitatory and inhibitory subfields or an obvious spectrotemporal slant in the
      STRF. These data provide the first detailed description of auditory receptive
      fields in the mouse and suggest that although neurons in areas AI and AAF share
      many response characteristics, area AAF may be specialized for faster temporal
      processing.

PMID- 12815017
TI  - Accuracy, information, and response time in a saccadic decision task.
AB  - Reaction times generally follow a simple law economically described by the LATER
      model, in which a decision signal rises linearly in response to information about
      a target to a threshold at which a response is initiated, at a rate that varies
      from trial to trial with a Gaussian distribution. Functionally, LATER may be
      regarded as an ideal decision mechanism incorporating prior probability,
      information, and criterion level or urgency; this can be tested quantitatively by
      seeing whether LATER accurately predicts the effects on latency distributions of
      manipulating these variables: in this case, information and urgency. We presented
      subjects with random-dot kinematograms while fixating a central LED. The
      information content of the display was varied by altering the proportion of the
      dots moving coherently together either left or right rather than randomly. As
      soon as subjects detected the direction of coherent movement, they made a saccade
      in the same direction to one of a pair of LEDs on each side of the fixation
      target. Subjects responded either carefully, taking time to ensure an accurate
      judgement, or more hastily and with less regard for accuracy. The distributions
      of latencies under the different combinations of conditions were found to conform
      to LATER's predictions. Providing more information or increasing urgency both
      reduce latency; but they alter the observed distributions in different ways,
      equivalent to increasing the mean rate of rise on the one hand or reducing the
      criterion level on the other. Making only simple assumptions about the underlying
      mechanisms, the observed changes can be accounted for quantitatively.

PMID- 12815018
TI  - Capsaicin infused into the PAG affects rat tail flick responses to noxious heat
      and alters neuronal firing in the RVM.
AB  - It is well established that the vanilloid receptor, VR1, is an important
      peripheral mediator of nociception. VR1 receptors are also located in several
      brain regions, yet it is uncertain whether these supraspinal VR1 receptors have
      any influence on the nociceptive system. To investigate a possible nociceptive
      role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 microl) was
      microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the
      periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion
      in 52 degrees C water) and on neuronal activity (on-, off-, and neutral cells) in
      the rostral ventromedial medulla (RVM) were measured in lightly anesthetized
      rats. Administration of capsaicin into the dPAG but not the vPAG caused an
      initial hyperalgesic response followed later by analgesia (125 +/- 20.96 min
      postinjection). The tail flick-related burst in on-cell activity was triggered
      earlier in the hyperalgesic phase and was delayed or absent during the analgesic
      phase. Spontaneous activity of on-cells increased at the onset of the
      hyperalgesic phase and decreased before and during the analgesic phase. The tail
      flick-related pause in off-cell activity as well as spontaneous firing for these
      cells was unchanged in the hyperalgesic phase. During the analgesic phase, off
      cells no longer paused during noxious stimulation and had increased levels of
      spontaneous activity. Neutral cell firing was unaffected in either phase.
      Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4
      microl), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the
      corresponding changes in on- and off-cell activity. VR1 receptor immunostaining
      was observed in the dPAG of untreated rats. Microinjection of capsaicin likely
      sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and
      RVM neuronal activity. These results suggest that supraspinal VR1 receptors in
      the dPAG contribute to descending modulation of nociception.

PMID- 12815019
TI  - Interaction between gaze and pointing toward remembered visual targets.
AB  - We examined the role of gaze in a task where subjects had to reproduce the
      position of a remembered visual target with the tip of the index finger, referred
      to as pointing. Subjects were tested in 3 visual feedback conditions: complete
      darkness (dark), complete darkness with visual feedback of the finger position
      (finger), and with vision of a well-defined environment and feedback of the
      finger position (frame). Pointing accuracy increases with feedback about the
      finger or visual environment. In the finger and frame conditions, the 95%
      confidence regions of the variable errors have an ellipsoidal distribution with
      the main axis oriented toward the subjects' head. During the 1-s period when the
      target is visible, gaze is almost on target. However, gaze drifts away from the
      target relative to the subject in the delay period after target disappearance. In
      the finger and frame conditions, gaze returns toward the remembered target during
      pointing. In all 3 feedback conditions, the correlations between the variable
      errors of gaze and pointing position increase during the delay period, reaching
      highly significant values at the time of pointing. Our results demonstrate that
      gaze affects the accuracy of pointing. We conclude that the covariance between
      gaze and pointing position reflects a common drive for gaze and arm movements and
      an effect of gaze on pointing accuracy at the time of pointing. Previous studies
      interpreted the orientation of variable errors as indicative for a frame of
      reference used for pointing. Our results suggest that the orientation of the
      error ellipses toward the head is at least partly the result of gaze drift in the
      delay period.

PMID- 12815020
TI  - Contribution of synaptic depression to phase maintenance in a model rhythmic
      network.
AB  - In many rhythmic neuronal networks that operate in a wide range of frequencies,
      the time of neuronal firing relative to the cycle period (the phase) is
      invariant. This invariance suggests that when frequency changes, firing time is
      precisely adjusted either by intrinsic or synaptic mechanisms. We study the
      maintenance of phase in a computational model in which an oscillator neuron (O)
      inhibits a follower neuron (F) by comparing the dependency of phase on cycle
      period in two cases: when the inhibitory synapse is depressing and when it is
      nondepressing. Of the numerous ways of changing the cycle period, we focus on
      three cases where either the duration of the active state, the inactive state, or
      the duty cycle of neuron O remains constant. In each case, we measure the phase
      at which neuron F fires with respect to the onset of firing in neuron O. With a
      nondepressing synapse, this phase is generally a monotonic function of cycle
      period except in a small parameter range in the case of the constant inactive
      duration. In contrast, with a depressing synapse, there is always a parameter
      regime in which phase is a cubic function of cycle period: it decreases at short
      cycle periods, increases in an intermediate range, and decreases at long cycle
      periods. This complex shape for the phase-period relationship arises because of
      the interaction between synaptic dynamics and intrinsic properties of the
      postsynaptic neuron. By choosing appropriate parameters, the cubic shape of the
      phase-period curve results in a small variation in phase for a large interval of
      periods. Consequently, we find that although a depressing synapse does not
      produce perfect phase maintenance, in most cases it is superior to a
      nondepressing synapse in promoting a constant phase difference.

PMID- 12815021
TI  - Activation of peripheral NMDA receptors contributes to human pain and rat
      afferent discharges evoked by injection of glutamate into the masseter muscle.
AB  - Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and
      may play a role in deep tissue pain. Injection of the endogenous NMDA receptor
      agonist glutamate into the masseter muscle excites deep craniofacial afferent
      fibers in rats and evokes pain in human subjects. It is not clear whether
      peripheral NMDA receptors play a role in these effects of glutamate. Accordingly,
      the effect of NMDA on afferent activity as well as the effect of locally
      administered NMDA receptor antagonists on glutamate-evoked afferent discharges in
      acutely anesthetized rats and muscle pain in human subjects was examined.
      Injection of NMDA into the masseter muscle evoked afferent discharges in a
      concentration-related manner. It was found that the NMDA receptor antagonists 2
      amino-5-phosphonvalerate (APV, 10 mM), ketamine (10 mM), and dextromethorphan (40
      mM) significantly decreased glutamate-evoked afferent discharges. The effects of
      APV and ketamine, but not dextromethorphan, were selective for glutamate-evoked
      afferent discharges and did not affect hypertonic saline-evoked afferent
      discharges. In human experiments, it was found that 10 mM ketamine decreased
      glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle
      pain. These results indicate that injection of glutamate into the masseter muscle
      evokes afferent discharges in rats and muscle pain in humans in part through
      activation of peripheral NMDA receptors. It is conceivable that activation of
      peripheral NMDA receptors may contribute to masticatory muscle pain and that
      peripherally acting NMDA receptor antagonists could prove to be effective
      analgesics for this type of pain.

PMID- 12815022
TI  - Anesthetic treatment blocks synaptogenesis but not neuronal regeneration of
      cultured Lymnaea neurons.
AB  - Trauma and injury necessitate the use of various surgical interventions, yet such
      procedures themselves are invasive and often interrupt synaptic communications in
      the nervous system. Because anesthesia is required during surgery, it is
      important to determine whether long-term exposure of injured nervous tissue to
      anesthetics is detrimental to regeneration of neuronal processes and synaptic
      connections. In this study, using identified molluscan neurons, we provide direct
      evidence that the anesthetic propofol blocks cholinergic synaptic transmission
      between soma-soma paired Lymnaea neurons in a dose-dependent and reversible
      manner. These effects do not involve presynaptic secretory machinery, but rather
      postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover,
      we discovered that long-term (18-24 h) anesthetic treatment of soma-soma paired
      neurons blocked synaptogenesis between these cells. However, after several hours
      of anesthetic washout, synapses developed between the neurons in a manner similar
      to that seen in vivo. Long-term anesthetic treatment of the identified neurons
      visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically
      coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell
      culture as the neurons continued to exhibit extensive neurite outgrowth. However,
      these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical
      (PeA) synapses as observed in their control counterparts. After drug washout,
      appropriate synapses did reform between the cells, although this synaptogenesis
      required several days. Taken together, this study provides the first direct
      evidence that the clinically used anesthetic propofol does not affect nerve
      regeneration. However, the formation of both chemical and electrical synapses is
      severely compromised in the presence of this drug. This study emphasizes the
      importance of short-term anesthetic treatment, which may be critical for the
      restoration of synaptic connections between injured neurons.

PMID- 12815023
TI  - Spinal neuronal responses to urinary bladder stimulation in rats with
      corticosterone or aldosterone onto the amygdala.
AB  - Elevating glucocorticoids in the amygdala produces colorectal hypersensitivity
      through activation of lumbosacral spinal neurons. The aim of this study was to
      determine if descending modulation from the amygdala affects spinal processing of
      input from urinary bladder afferents. Fischer-344 rats received cholesterol
      (inactive control)-, corticosterone-, or aldosterone-containing micropellets
      placed stereotaxically on the dorsal margin of the left and right amygdala (n =
      10 for each group). Seven days after amygdaloid implantation, extracellular
      potentials of single L6-S1 spinal neurons were examined for the responses to
      graded (0.5-2.0 ml, 20 s) urinary bladder distension (UBD). Spontaneous activity
      of neurons with excitatory responses to UBD in aldosterone-implanted rats [11.0
      +/- 1.7 (SE) imp/s], but not in corticosterone-implanted rats, was higher than in
      the cholesterol-implanted group (6.6 +/- 1.1 imp/s, P < 0.05). Noxious UBD (1.5
      ml) produced a greater excitatory response (21.6 +/- 2.6 imp/s) in aldosterone
      implanted rats compared with cholesterol- or corticosterone-implanted rats (15.1
      +/- 1.5 and 13.6 +/- 1.4 imp/s; P < 0.05). In contrast, the duration of
      excitatory responses to UBD in corticosterone-implanted rats (38.5 +/- 3.4 imp/s)
      was significantly longer than those in the aldosterone or control groups (26.8 +/
      1.8 and 24.7 +/- 1.5 imp/s). Neurons with low thresholds for excitatory
      responses to UBD were seen more frequently in aldosterone-implanted rats than in
      corticosterone or cholesterol treated rats (74 vs. 44% and 39%, P < 0.05). No
      difference in somatic field properties of spinal neurons responsive or
      nonresponsive to UBD was found among the three groups. These findings suggest
      that both mineralocorticoid- and glucocorticoid-mediated mechanisms in the
      amygdala are involved in descending modulation to lumbosacral spinal neurons
      receiving inputs from the urinary bladder; and this mechanism may play a role in
      the activation and maintenance of primary central sensitization to noxious
      visceral stimuli.

PMID- 12815024
TI  - Incomplete functional subdivision of the human multitendoned finger muscle flexor
      digitorum profundus: an electromyographic study.
AB  - The human flexor digitorum profundus (FDP) sends tendons to all 4 fingers. One
      might assume that this multitendoned muscle consists of 4 discrete neuromuscular
      compartments each acting on a different finger, but recent anatomical and
      physiological studies raise the possibility that the human FDP is incompletely
      subdivided. To investigate the functional organization of the human FDP, we
      recorded electromyographic (EMG) activity by bipolar fine-wire electrodes
      simultaneously from 2 or 4 separate intramuscular sites as normal human subjects
      performed isometric, individuated flexion, and extension of each left-hand digit.
      Some recordings showed EMG activity during flexion of only one of the 4 fingers,
      indicating that the human FDP has highly selective core regions that act on
      single fingers. The majority of recordings, however, showed a large amount of EMG
      activity during flexion of one finger and lower levels of EMG activity during
      flexion of an adjacent finger. This lesser EMG activity during flexion of
      adjacent fingers was unlikely to have resulted from recording motor units in
      neighboring neuromuscular compartments, and instead suggests incomplete
      functional subdivision of the human FDP. In addition to the greatest agonist EMG
      activity during flexion of a given finger, most recordings also showed EMG
      activity during extension of adjacent fingers, apparently serving to stabilize
      the given finger against unwanted extension. Paradoxically, the functional
      organization of the human FDP-with both incomplete functional subdivision and
      highly selective core regions-may contribute simultaneously to the inability of
      humans to produce completely independent finger movements, and to the greater
      ability of humans (compared with macaques) to individuate finger movements.

PMID- 12815025
TI  - Two dynamically distinct inhibitory networks in layer 4 of the neocortex.
AB  - Normal operations of the neocortex depend critically on several types of
      inhibitory interneurons, but the specific function of each type is unknown. One
      possibility is that interneurons are differentially engaged by patterns of
      activity that vary in frequency and timing. To explore this, we studied the
      strength and short-term dynamics of chemical synapses interconnecting local
      excitatory neurons (regular-spiking, or RS, cells) with two types of inhibitory
      interneurons: fast-spiking (FS) cells, and low-threshold spiking (LTS) cells of
      layer 4 in the rat barrel cortex. We also tested two other pathways onto the
      interneurons: thalamocortical connections and recurrent collaterals from
      corticothalamic projection neurons of layer 6. The excitatory and inhibitory
      synapses interconnecting RS cells and FS cells were highly reliable in response
      to single stimuli and displayed strong short-term depression. In contrast,
      excitatory and inhibitory synapses interconnecting the RS and LTS cells were less
      reliable when initially activated. Excitatory synapses from RS cells onto LTS
      cells showed dramatic short-term facilitation, whereas inhibitory synapses made
      by LTS cells onto RS cells facilitated modestly or slightly depressed.
      Thalamocortical inputs strongly excited both RS and FS cells but rarely and only
      weakly contacted LTS cells. Both types of interneurons were strongly excited by
      facilitating synapses from axon collaterals of corticothalamic neurons. We
      conclude that there are two parallel but dynamically distinct systems of synaptic
      inhibition in layer 4 of neocortex, each defined by its intrinsic spiking
      properties, the short-term plasticity of its chemical synapses, and (as shown
      previously) an exclusive set of electrical synapses. Because of their unique
      dynamic properties, each inhibitory network will be recruited by different
      temporal patterns of cortical activity.

PMID- 12815026
TI  - GABA transporter-1 (GAT1)-deficient mice: differential tonic activation of GABAA
      versus GABAB receptors in the hippocampus.
AB  - After its release from interneurons in the CNS, the major inhibitory
      neurotransmitter GABA is taken up by GABA transporters (GATs). The predominant
      neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve
      terminals, where it is thought to influence GABAergic synaptic transmission, but
      the details of this regulation are unclear. To address this issue, we have
      generated a strain of GAT1-deficient mice. We observed a large increase in a
      tonic postsynaptic hippocampal GABAA receptor-mediated conductance. There was
      little or no change in the waveform or amplitude of spontaneous inhibitory
      postsynaptic currents (IPSCs) or miniature IPSCs. In contrast, the frequency of
      quantal GABA release was one-third of wild type (WT), although the densities of
      GABAA receptors, GABAB receptors, glutamic acid decarboxylase 65 kDa, and
      vesicular GAT were unaltered. The GAT1-deficient mice lacked a presynaptic GABAB
      receptor tone, present in WT mice, which reduces the frequency of spontaneous
      IPSCs. We conclude that GAT1 deficiency leads to enhanced extracellular GABA
      levels resulting in an overactivation of GABAA receptors responsible for a
      postsynaptic tonic conductance. Chronically elevated GABA levels also
      downregulate phasic GABA release and reduce presynaptic signaling via GABAB
      receptors thus causing an enhanced tonic and a diminished phasic inhibition.

PMID- 12815027
TI  - Dendritic projections and dye-coupling in dopaminergic neurons of the substantia
      nigra examined in horizontal brain slices from young rats.
AB  - We examined the rostro-caudal dendritic spread of striatally projecting
      dopaminergic neurons of the Substantia Nigra pars compacta (SNc) and investigated
      the presence of dye-coupling after labeling these cells with a mixture of lucifer
      yellow (LY) and neurobiotin (NB) or with LY alone. Whole cell recordings were
      made from horizontal brain slices (400 microm) obtained from P5-P20 rats. SNc
      neurons retrogradely labeled with Fluoro-Gold and located in the region
      containing tyrosine hydroxylase-immunoreactive cells displayed Ih current and
      other properties characteristic of SNc neurons. To prevent extracellular leakage,
      dyes were introduced into patch pipettes after the establishment of whole cell
      configuration, and cells were filled under visual control. In contrast to
      previous studies conducted in coronal sections that identified dendritic
      projections of SNc neurons mainly in the medio-lateral and ventral directions,
      almost all neurons labeled in our study (53/54) additionally displayed a large
      rostro-caudal dendritic span (649 +/- 219 microm). Dye-coupling between SNc
      neurons was not observed under basal conditions, in the presence of gap junction
      "openers" (forskolin, trimethylamine), or after neurons were filled with LY using
      sharp intracellular microelectrodes. As a "positive control," dye-coupling was
      demonstrated in four hippocampal dentate gyrus neurons that were filled using the
      same patch pipette technique. In addition, none of the tested SNc cells (n = 12)
      showed expression of connexin 36 (the "neuronal" connexin) when tested with
      single-cell RT-PCR. In conclusion, this study revealed extensive rostro-caudal
      dendritic projections of SNc neurons. Under our in vitro conditions, no evidence
      was found for dye-coupling among these neurons.

PMID- 12815028
TI  - Volatile communication between barley plants affects biomass allocation.
AB  - Patterns of biomass allocation between different plant organs have often been
      used to explain the response of plants to variations in resource availability.
      This paper reports how aerial allelopathy (plant-plant communication) affects
      biomass allocation, that is the trade-off between root, stem and leaves, and also
      relative growth rate (RGR, increase in biomass per unit biomass per unit of time,
      mg g-1 d-1) and its components. Based on previous experiments, communication
      between two barley (Hordeum vulgare L.) cultivars (Alva and Kara) was used for
      the present study. Kara exposed to volatiles from Alva allocated significantly
      more biomass to roots compared with Kara exposed to volatiles from Kara or to
      clean air. There was no significant difference between plants of Kara exposed to
      volatiles from Kara and those exposed to clean air. Changes in total dry weight
      (TDW), RGR and unit leaf rate (ULR, increase in biomass per unit time and leaf
      area, kg m-2 d-1) were not significantly affected by plant-plant communication.
      However, there was a significant increase in specific leaf area (SLA, leaf area
      per leaf dry weight, m2 kg-1) in Kara when exposed to volatiles from Alva. The
      results show that aerial plant-plant communication does not affect total biomass
      production but does significantly affect biomass allocation in individual plants.
      There may be differences in the volatile profiles of Kara and Alva that induce
      increased biomass allocation to roots in the Kara plants exposed to volatiles
      from Alva.

PMID- 12815029
TI  - Ecophysiological relevance of cuticular transpiration of deciduous and evergreen
      plants in relation to stomatal closure and leaf water potential.
AB  - The water permeability of the leaves of three deciduous plants (Acer campestre,
      Fagus sylvatica, Quercus petraea) and two evergreen plants (Hedera helix, Ilex
      aquifolium) was analysed in order to assess its role as a mechanism of drought
      resistance. Cuticular permeances were determined by measurement of the water loss
      through adaxial, astomatous leaf surfaces. Minimum conductances after complete
      stomatal closure were obtained by leaf drying curves. The comparison of the water
      permeabilities determined with these two experimental systems revealed good
      agreement in the case of Acer, Fagus, Quercus, and Ilex. For Hedera the minimum
      conductance was 3-fold higher than the cuticular permeance indicating a
      significant contribution of residual stomatal transpiration. The leaf water
      potential was measured as a function of water content and analysed by pressure
      volume curves. The influence of water potential as a component of the driving
      force for transpirational water loss was assessed in order to identify
      modifications of the cuticular barrier by the leaf water content. The
      ecophysiological meaning of the water relations parameters describing
      transpiration under drought conditions (cuticular transpiration, minimum
      transpiration, residual stomatal transpiration, effect of leaf water content on
      transpiration) and the water relations parameters derived from pressure-volume
      curves (osmotic potential at full saturation, turgor loss point, bulk modulus of
      elasticity) are discussed with regard to adaptations for drought resistance.

PMID- 12815030
TI  - Elevated sucrose-phosphate synthase activity in transgenic tobacco sustains
      photosynthesis in older leaves and alters development.
AB  - Constitutive over-expression of a maize sucrose-phosphate synthase (SPS) gene in
      tobacco (Nicotiana tabacum) had major effects on leaf carbohydrate budgets with
      consequences for whole plant development. Transgenic tobacco plants flowered
      earlier and had greater flower numbers than wild-type plants. These changes were
      not linked to modified source leaf carbon assimilation or carbon export, although
      sucrose to starch ratios were significantly higher in leaves expressing the
      transgene. The youngest and oldest leaves of plants over-expressing SPS had up to
      10-fold wild-type maximal extractable SPS activity, but source leaf SPS
      activities were only 2-3 times greater in these lines than in the wild type. In
      the oldest leaves, where the expression of the transgene led to the most marked
      enhancement in SPS activity, photosynthesis was also increased. It was concluded
      that these increases in the capacity for sucrose synthesis and carbon
      assimilation, particularly in older leaves, accelerate the whole plant
      development and increase the abundance of flowers without substantial changes in
      the overall shoot biomass.

PMID- 12815031
TI  - A cell wall-oriented genomic approach reveals a new and unexpected complexity of
      the softening in peaches.
AB  - During ripening, fleshy fruits undergo textural changes that lead to loss of
      tissue firmness and consequent softening. It is a common idea that this process
      is the consequence of cell wall dismantling carried out by different and orderly
      expressed enzymes. For this purpose, by using a single enzyme family approach
      many enzymes and related genes have been characterized in different fruits. In
      this work, the softening of the climacteric peach fruits (Prunus persica (L.)
      Batsch.) has been studied by using a genomic approach, and the results obtained
      are novel and partly unexpected. The genes analysed encode proteins involved in
      the main metabolic aspects of a primary cell wall: degradation, synthesis,
      structure. In addition, some genes encoding cell-wall-related proteins with an
      unknown function have been studied. The gene expression profiles show that the
      softening actually begins well before the climacteric rise and continues
      thereafter. Genes whose expression starts before the climacteric rise are mostly
      down-regulated by ethylene, while genes with a ripening-specific expression are
      mostly up-regulated by the hormone. A few other genes are apparently insensitive
      to ethylene. Besides the expected parietal degradation, the softening that
      results from this study also comprises some repairing of the cell wall performed
      by enzymes involved in the synthesis of parietal polysaccharides and, especially,
      by proteins with structural functions. The newly synthesized polysaccharides and
      the structural proteins would thus help to hold together the fruit cell wall
      while not preventing the softening.

PMID- 12815032
TI  - Significance of skin flavonoids for UV-B-protection in apple fruits.
AB  - An attempt has been made to assess the UV-B-protective capacity of phenolic
      compounds accumulated in superficial structures of plants using apple fruit as a
      model. Two apple (Malus domestica Borkh.) cultivars (Braeburn and Granny Smith)
      differing in response to high fluxes of solar radiation were selected and exposed
      to increasing doses of UV-B radiation. The extent of UV-B-induced damage to
      photosystem II of apple skin correlated with its quercetin glycoside (but not
      anthocyanin) content. Granny Smith apples did not demonstrate a pronounced
      response to high sunlight in terms of the accumulation of phenolic substances in
      the skin and exhibited similar patterns of Fo, Fm, and Fv/Fm changes in the
      course of UV-B irradiation both on sun-exposed and shaded surfaces of a fruit.
      Unlike Granny Smith, Braeburn fruits were characterized by a significant
      accumulation of quercetin glycosides in sun-exposed skin, however, shaded skin
      contained these compounds in similar amounts to those in Granny Smith.
      Accordingly, photosystem II in sun-exposed skin of Braeburn apples was resistant
      to high doses of UV-B radiation (up to 97 kJ m-2), whereas the susceptibility of
      the photosynthetic apparatus in shaded skin of Braeburn to UV-B-induced damage
      was much higher and similar to that of both sun-exposed and shaded skin of Granny
      Smith fruits. Anthocyanins, at least in the amounts found in Braeburn, did not
      show an additional effect in UV-B protection.

PMID- 12815033
TI  - OsSET1, a novel SET-domain-containing gene from rice.
AB  - A novel SET-domain-containing gene OsSET1 was isolated from rice (Oryza sativa
      L.). Its deduced protein consists of 895 amino acids. OsSET1 has a high degree of
      structure similarity to other SET-domain-containing genes such as CLF in higher
      plants and E(z) in animals. RT-PCR showed that the gene expresses throughout the
      entire plant. A transient expression assay in onion epidermis revealed that the
      OsSET1 protein is localized in nuclei. Over-expression of the SET domain of
      OsSET1 in Arabidopsis resulted in altered shoot development at seedling stages.

PMID- 12815034
TI  - Air method measurements of apple vessel length distributions with improved
      apparatus and theory.
AB  - Studies showing that rootstock dwarfing potential is related to plant hydraulic
      conductance led to the hypothesis that xylem properties are also related. Vessel
      length distribution and other properties of apple wood from a series of varieties
      were measured using the 'air method' in order to test this hypothesis. Apparatus
      was built to measure and monitor conductivity to air of fresh wood segments of
      different lengths. Theory for determining vessel length distribution was improved
      to give a single parameter uni-modal vessel length probability density function.
      The function, derived by combining the exponential extinction (with extinction
      coefficient k) of wood conductivity to air (C) as wood length (x) increases (i.e.
      C=Co exp (-kx)) with the differential double difference formula, is Px=xxk2 exp (
      kx), where Px is the fraction of vessels of length x. The main parameter of the
      distribution, k, was found to be the inverse of the mode of the distribution,
      i.e. the most common vessel length, Lo. Lo for ten apple rootstock and scion
      varieties varied from 5.6+/-0.1 cm (+/-SE) for MM.111 to 9.0+/-1.0 for Prunifolia
      (P <0.05). Average maximum vessel length was approximately 50 cm, and differences
      were not significant. Effective vessel radii ranged from 14 for Prunifolia to
      24.3+/-0.7 micro m for M.26, with standard errors less than 12% of the mean.
      Specific conductivity of a 15 cm wood segment ranged from 2x109-4) to 1.6+/
      0.2x10(-2) dm3 s(-1) kPa(-1) m(-1) for maruba and M.26, respectively, with
      standard errors up to 63% of the mean. Vessel density at the air entry point
      ranged from 18+/-3 to 42+/-6 vessels mm-2 for M.26 and MM.106, respectively, with
      standard errors as high as 89% of the mean. It was concluded that there is no
      general relationship between the wood properties investigated and rootstock size
      class, and that plasticity increases from vessel lengths to radii to specific
      conductivity and vessel densities.

PMID- 12815035
TI  - Cloning and expression of a UDP-glucuronic acid decarboxylase gene in rice.
AB  - A cDNA fragment was cloned from rice immature seeds by the RT-PCR method. The
      deduced amino acid sequence of the cDNA showed a high degree of identity with UDP
      d-glucuronic acid decarboxylase (UXS) from other plants and was most similar to
      the soluble UXS from Arabidopsis. The recombinant protein, expressed in an
      Escherichia coli system, catalysed the conversion of UDP-d-glucuronic acid to UDP
      d-xylose, confirming that the gene encoded UXS. The uxs gene was expressed in
      mature, harvested rice seeds as well as in immature seeds 14 d post-anthesis,
      suggesting that the uxs gene is necessary at the beginning of the germination
      period. This is the first report of the cloning of the uxs gene from monocots.

PMID- 12815036
TI  - Phytochelatin synthase (PCS) protein is induced in Brassica juncea leaves after
      prolonged Cd exposure.
AB  - Higher plants respond to cadmium exposure with the production of phytochelatins
      (PCn), small heavy metal binding peptides, which are synthesized from glutathione
      by phytochelatin synthase (PCS). The isolation of a PCS cDNA clone from Brassica
      juncea L. cv. Vitasso, a candidate species for phytoremediation, is reported
      here. CLUSTAL analysis revealed a close relationship of BjPCS1 with PCS proteins
      from Arabidopsis thaliana and Thlaspi caerulescens. BjPCS1 expressed as
      recombinant protein in E. coli had PCS activity in vitro that was activated by 50
      microM Cu and 200 microM Cd to a similar extent. Immunoblot analysis with an
      antiserum directed against recombinant BjPCS1 showed constitutive PCS expression
      during plant development. As a percentage of the total protein, the expression
      was higher in the roots, internodes and petioles in comparison with the leaf
      tissue. When B. juncea plants were treated with 25 microM cadmium, PCn
      accumulated increasingly over a 6 d period. Levels in shoots were about 3-fold
      higher than in roots. Prolonged cadmium exposure caused a significant increase of
      PCS protein in leaves, whereas in roots PCS protein levels were not affected.

PMID- 12815037
TI  - Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor
      produces desensitization and internalization.
AB  - G-protein receptor kinase and beta-arrestin mediated desensitization of the rat
      kappa-opioid receptor (KOR) was previously shown using Xenopus oocyte expression
      to require serine 369 within the C terminus of KOR. To define the effects of
      phosphorylation of this residue in desensitization and internalization processes
      in mammalian expression systems, wild-type KOR-green fluorescent protein (KOR
      GFP) and KOR(S369A)-GFP were stably expressed in AtT-20 and HEK293 cells. Using
      whole-cell patch clamp recording in transfected AtT-20 cells, agonist activation
      of either kappa receptor form produced equivalent activation of the intrinsic G
      protein-gated inwardly rectifying potassium channel. Incubation for 60 min with
      the kappa agonist U50,488 (100 nm) desensitized the response in cells expressing
      wild-type KOR-GFP by 86% but had no effect on KOR(S369A)-GFP-expressing cells.
      Phosphorylation of serine 369 was detected using a phosphospecific antibody (KOR
      P) able to distinguish the phosphorylated form of the receptor. The agonist
      induced increase in KOR-P labeling was dose-dependent, blocked by co-treatment
      with the kappa antagonist norbinaltorphimine, and prevented by co-expression of
      the dominant negative form of the G-protein receptor kinase, GRK2(K220R). In
      contrast, agonist-induced increase in KOR-P labeling was not evident in
      KOR(S369A) expressing cells. Prolonged activation resulted in receptor
      internalization that was also blocked by KOR(S369A) substitution, but
      interestingly, KOR-P labeling was evident at lower agonist concentrations than
      required to induce internalization. Following the removal of agonist, receptor
      dephosphorylation detected by loss of KOR-P labeling was complete within 60 min,
      could be blocked by okadaic acid, and was not blocked by sucrose inhibition of
      receptor internalization. These results demonstrate that GRK-mediated
      phosphorylation of serine 369 mediates rat KOR desensitization and
      internalization.

PMID- 12815038
TI  - Albumin is a substrate of human chymase. Prediction by combinatorial peptide
      screening and development of a selective inhibitor based on the albumin cleavage
      site.
AB  - Human chymase is a chymotryptic serine peptidase stored and secreted by mast
      cells. Compared with other chymotryptic enzymes, such as cathepsin G and
      chymotrypsin, it is much more slowly inhibited by serum serpins. Although chymase
      hydrolyzes several peptides and proteins in vitro, its target repertoire is
      limited compared with chymotrypsin because of selective interactions in an
      extended substrate-binding site. The best-known natural substrate, angiotensin I,
      is cleaved to generate vasoactive angiotensin II. Selectivity of angiotensin
      cleavage depends in major part on interactions involving substrate residues on
      the carboxyl-terminal (P1'-P2') side of the cleaved bond. To identify new targets
      based on interactions with residues on the aminoterminal (P4-P1) side of the site
      of hydrolysis, we profiled substrate preferences of recombinant human chymase
      using a combinatorial, fluorogenic peptide substrate library. Data base queries
      using the peptide (Arg-Glu-Thr-Tyr-X) generated from the most preferred amino
      acid at each subsite identify albumin as the sole, soluble, human extracellular
      protein containing this sequence. We validate the prediction that this site is
      chymase-susceptible by showing that chymase hydrolyzes albumin uniquely at the
      predicted location, with the resulting fragments remaining disulfide-linked. The
      site of hydrolysis is highly conserved in vertebrate albumins and is near
      predicted sites of metal cation binding, but nicking by chymase does not alter
      binding of Cu2+ or Zn2+. A synthetic peptidic inhibitor, diphenyl N alpha
      benzoxycarbonyl-l-Arg-Glu-Thr-PheP-phosphonate, was designed from the preferred
      P4-P1 substrate sequence. This inhibitor is highly potent (IC50 3.8 nM) and 2,700
      and 1,300-fold selective for chymase over cathepsin G and chymotrypsin,
      respectively. In summary, these findings reveal albumin to be a substrate for
      chymase and identify a potentially useful new chymase inhibitor.

PMID- 12815040
TI  - Identification and characterization of murine SCD4, a novel heart-specific
      stearoyl-CoA desaturase isoform regulated by leptin and dietary factors.
AB  - Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in the biosynthesis of
      monounsaturated fatty acids. Thus far, three isoforms of SCD (SCD1, SCD2, and
      SCD3) have been identified and characterized. Regulation of the SCD1 isoform has
      been shown to be an important component of the metabolic actions of leptin in
      liver, but the effects of leptin on SCD isoforms in other tissues have not been
      investigated. We found that although the mRNA levels of SCD1 and SCD2 were not
      affected by leptin deficiency in the hearts of ob/ob mice, the SCD activity and
      levels of monounsaturated fatty acids were increased, implying the existence of
      another SCD isoform. This observation has led to the cDNA cloning and
      characterization of a fourth SCD isoform (SCD4) that is expressed exclusively in
      the heart. SCD4 encodes a 352-amino acid protein that shares 79% sequence
      identity with the SCD1, SCD2, and SCD3 isoforms. Liver X receptor alpha (LXR
      alpha) agonists and a high carbohydrate fat-free diet induced SCD4 expression,
      but unlike SCD1, SCD4 expression was not repressed by dietary polyunsaturated
      fatty acids. SCD4 mRNA levels were elevated 5-fold in the hearts of leptin
      deficient ob/ob mice relative to wild type controls. Treatment of ob/ob mice with
      leptin decreased mRNA levels of SCD4, whereas levels of SCD1 and SCD2 were not
      affected. Furthermore, in the hearts of SCD1-deficient mice, SCD4 mRNA levels
      were induced 3-fold, whereas the levels of SCD2 were not altered. The current
      studies identify a novel heart-specific SCD isoform that demonstrates tissue
      specific regulation by leptin and dietary factors.

PMID- 12815039
TI  - Tissue expression, protease specificity, and Kunitz domain functions of
      hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of
      HAI-1.
AB  - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is an integral membrane
      protein expressed on epithelial cells and contains two extracellular Kunitz
      domains (N-terminal KD1 and C-terminal KD2) known to inhibit trypsin-like serine
      proteases. In tumorigenesis and tissue regeneration, HAI-1 regulates the
      hepatocyte growth factor (HGF)/c-Met pathway by inhibiting the activity of HGF
      activator (HGFA) and matriptase, two serine proteases that convert pro-HGF into
      its biologically active form. By screening a placental cDNA library, we
      discovered a new splice variant of HAI-1 designated HAI-1B that contains an extra
      16 amino acids adjacent to the C terminus of KD1. To investigate possible
      consequences on Kunitz domain function, a soluble form of HAI-1B (sHAI-1B)
      comprising the entire extracellular domain was produced. First, we found that
      sHAI-1B displayed remarkable enzyme specificity by potently inhibiting only HGFA
      (IC50 = 30.5 nm), matriptase (IC50 = 16.5 nm), and trypsin (IC50 = 2.4 nm) among
      16 serine proteases examined, including plasminogen activators (urokinase- and
      tissue-type plasminogen activators), coagulation enzymes thrombin, factors VIIa,
      Xa, XIa, and XIIa, and activated protein C. Relatively weak inhibition was found
      for plasmin (IC50 = 399 nm) and plasma kallikrein (IC50 = 686 nm). Second, the
      functions of the KD1 and KD2 domains in sHAI-1B were investigated using P1
      residue-directed mutagenesis to show that inhibition of HGFA, matriptase,
      trypsin, and plasmin was due to KD1 and not KD2. Furthermore, analysis by reverse
      transcription-PCR demonstrated that HAI-1B and HAI-1 were co-expressed in normal
      tissues and various epithelial-derived cancer cell lines. Both isoforms were up
      regulated in eight examined ovarian carcinoma specimens, three of which had
      higher levels of HAI-1B RNA than of HAI-1 RNA. Therefore, previously demonstrated
      roles of HAI-1 in various physiological and pathological processes likely involve
      both HAI-1B and HAI-1.

PMID- 12815041
TI  - Roles of glycosylphosphatidylinositols of Toxoplasma gondii. Induction of tumor
      necrosis factor-alpha production in macrophages.
AB  - Toxoplasma gondii is a ubiquitous parasitic protozoan, which causes congenital
      infectious diseases as well as severe encephalitis, a major cause of death among
      immune-deficient persons, such as AIDS patients. T. gondii is normally controlled
      by the immune system of healthy individuals, leading to an asymptomatic
      infection. T. gondii triggers early cytokine production, which, to a certain
      extent, protects the host against replication of tachyzoites, the infective form
      of the parasite. Glycosylphosphatidylinositols (GPIs) constitute a class of
      glycolipids that have various functions, the most fundamental being to link
      proteins to eucaryotic cell membranes. GPIs are involved in the pathogenicity of
      other protozoan parasites and are known to induce tumor necrosis factor-alpha
      (TNF alpha) production. We show that GPIs highly purified from T. gondii
      tachyzoites, as well as their core glycans, induce TNF alpha production in
      macrophages. A chemically synthesized GPI of T. gondii lacking its lipid moiety,
      GPIa, has the same effect as the natural GPIs, whereas a chemically synthesized
      molecule with dialkylglycerol instead of diacylglycerol as lipid moiety, GPIb,
      does not induce TNF alpha production. Moreover, GPIb inhibits the TNF alpha
      production induced by T. gondii GPI or by GPIa. The core glycan prepared from the
      two chemically synthesized molecules activates macrophages, showing that the
      lipid moiety may regulate signaling. Stimulation of macrophages with GPIs of T.
      gondii results in activation of the transcription factor NF-kappa B, which is
      inhibited by the chemically synthesized GPIb, suggesting the involvement of NF
      kappa B in TNF alpha gene expression. Our results support the idea that T. gondii
      GPIs are bioactive factors that participate in the production of TNF alpha during
      toxoplasmal pathogenesis.

PMID- 12815042
TI  - Regulation of transforming growth factor-beta signaling by protein inhibitor of
      activated STAT, PIASy through Smad3.
AB  - Smads proteins play a key role in the intracellular signaling of the transforming
      growth factor (TGF)-beta family of growth factors, which exhibits a diverse set
      of cellular responses, including cell proliferation and differentiation. In
      particular, Smad7 acts as an antagonist of TGF-beta signaling, which could
      determine the intensity or duration of its signaling cascade. In this study we
      identified a protein inhibitor of activated STAT (signal transducers and
      activators of transcription), PIASy, as a novel interaction partner of Smad7 by
      yeast two-hybrid screening using the MH2 domain of Smad7 as bait. The association
      of Smad7 and PIASy was confirmed using co-expressed tagged proteins in 293T
      cells. Moreover, we found that other Smads including Smad3 also associated with
      PIASy through its MH2 domain, and PIASy suppressed TGF-beta-mediated activation
      of Smad3. PIASy also stimulated the sumoylation of Smad3 in vivo. Furthermore,
      endogenous PIASy expression was induced by TGF-beta in Hep3B cells. These
      findings provide the first evidence that a PIAS family protein, PIASy, associates
      with Smads and involves the regulation of TGF-beta signaling using the negative
      feedback loop.

PMID- 12815043
TI  - Achromatopsia-associated mutation in the human cone photoreceptor cyclic
      nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore
      properties of heteromeric channels.
AB  - Cone photoreceptor cyclic nucleotide-gated (CNG) channels are thought to form by
      assembly of two different subunit types, CNGA3 and CNGB3. Recently, mutations in
      the gene encoding the CNGB3 subunit have been linked to achromatopsia in humans.
      Here we describe the functional consequences of two achromatopsia-associated
      mutations in human CNGB3 (hCNGB3). Co-expression in Xenopus oocytes of human
      CNGA3 (hCNGA3) subunits with hCNGB3 subunits containing an achromatopsia
      associated mutation in the S6 transmembrane domain (S435F) generated functional
      heteromeric channels that exhibited an increase in apparent affinity for both
      cAMP and cGMP compared with wild type heteromeric channels. In contrast, co
      expression of a presumptive null mutation of hCNGB3 (T383f.s.Delta C) with hCNGA3
      produced channels with properties indistinguishable from homomeric hCNGA3
      channels. The effect of hCNGB3 S435F subunits on cell-surface expression of green
      fluorescent protein-tagged hCNGA3 subunits and of non-tagged hCNGA3 subunits on
      surface expression of green fluorescent protein-hCNGB3 S435F subunits were
      similar to those observed for wild type hCNGB3 subunits, suggesting that the
      mutation does not grossly disturb subunit assembly or plasma membrane targeting.
      The S435F mutation was also found to produce changes in the pore properties of
      the channel, including decreased single channel conductance and decreased
      sensitivity to block by l-cis-diltiazem. Overall, these results suggest that the
      functional properties of cone CNG channels may be altered in patients with the
      S435F mutation, providing evidence supporting the pathogenicity of this mutation
      in humans. Thus, achromatopsia may arise from a disturbance of cone CNG channel
      gating and permeation or from the absence of functional CNGB3 subunits.

PMID- 12815044
TI  - Structural organization of alpha-synuclein fibrils studied by site-directed spin
      labeling.
AB  - Despite its importance in Parkinson's disease, a detailed understanding of the
      structure and mechanism of alpha-synuclein fibril formation remains elusive. In
      this study, we used site-directed spin labeling and electron paramagnetic
      resonance spectroscopy to study the structural features of monomeric and
      fibrillar alpha-synuclein. Our results indicate that monomeric alpha-synuclein,
      in solution, has a highly dynamic structure, in agreement with the notion that
      alpha-synuclein is a natively unfolded protein. In contrast, fibrillar aggregates
      of alpha-synuclein exhibit a distinct domain organization. Our data identify a
      highly ordered and specifically folded central core region of approximately 70
      amino acids, whereas the N terminus is structurally more heterogeneous and the C
      terminus ( approximately 40 amino acids) is completely unfolded. Interestingly,
      the central core region of alpha-synuclein exhibits several features reminiscent
      of those observed in the core region of fibrillar Alzheimer's amyloid beta
      peptide, including an in-register parallel structure. Although the lengths of the
      respective core regions differ, fibrils from different amyloid proteins
      nevertheless appear to be able to take up highly similar, and possibly conserved,
      structures.

PMID- 12815045
TI  - Role of troponin I phosphorylation in protein kinase C-mediated enhanced
      contractile performance of rat myocytes.
AB  - Our goal was to define the role of phosphorylated cardiac troponin-I in the adult
      myocyte contractile performance response to activated protein kinase C. In
      agreement with earlier work, endothelin enhanced both adult rat myocyte
      contractile performance and cardiac troponin-I phosphorylation. Protein kinase C
      participated in both responses. The role of cardiac troponin-I phosphorylation in
      the contractile function response to protein kinase C was further investigated
      using gene transfer into myocytes of troponin-I isoforms/mutants lacking one or
      more phosphorylation sites previously identified in purified cardiac troponin-I.
      Sarcomeric replacement with slow skeletal troponin-I-abrogated protein kinase C
      mediated troponin-I phosphorylation. In functional studies, endothelin slowed
      relaxation in myocytes expressing slow skeletal troponin-I, while the relaxation
      rate increased in myocytes expressing cardiac troponin-I. Based on these results,
      acceleration of myocyte relaxation during protein kinase C activation largely
      depended on cardiac troponin-I phosphorylation. Experiments with troponin-I
      isoform chimeras provided evidence that phosphorylation sites in the amino
      portion of cardiac troponin I-mediated the protein kinase C acceleration of
      relaxation. The cardiac troponin-I Thr-144 phosphorylation site identified in
      earlier biochemical studies was not significantly phosphorylated during the acute
      contractile response. Thus, amino-terminal protein kinase C-dependent
      phosphorylation sites in cardiac troponin-I are likely responsible for the
      accelerated relaxation observed in adult myocytes.

PMID- 12815046
TI  - Mechanisms of biosynthesis of mammalian copper/zinc superoxide dismutase.
AB  - Copper/zinc superoxide dismutase (SOD1) is an abundant intracellular enzyme with
      an essential role in antioxidant defense. The activity of SOD1 is dependent upon
      the presence of a bound copper ion incorporated by the copper chaperone for
      superoxide dismutase, CCS. To elucidate the cell biological mechanisms of this
      process, SOD1 synthesis and turnover were examined following 64Cu metabolic
      labeling of fibroblasts derived from CCS+/+ and CCS-/- embryos. The data indicate
      that copper is rapidly incorporated into both newly synthesized SOD1 and
      preformed SOD1 apoprotein, that each process is dependent upon CCS and that once
      incorporated, copper is unavailable for cellular exchange. The abundance of
      apoSOD1 is inversely proportional to the intracellular copper content and
      immunoblot and gel filtration analysis indicate that this apoprotein exists as a
      homodimer that is distinguishable from SOD1. Despite these distinct differences,
      the abundance and half-life of SOD1 is equivalent in CCS+/+ and CCS-/-
      fibroblasts, indicating that neither CCS nor copper incorporation has any
      essential role in the stability or turnover of SOD1 in vivo. Taken together,
      these data provide a cell biological model of SOD1 biosynthesis that is
      consistent with the concept of limited intracellular copper availability and
      indicate that the metallochaperone CCS is a critical determinant of SOD1 activity
      in mammalian cells. These kinetic and biochemical findings also provide an
      important framework for understanding the role of mutant SOD1 in the pathogenesis
      of familial amyotrophic lateral sclerosis.

PMID- 12815047
TI  - Regulation of proglucagon transcription by activated transcription factor (ATF) 3
      and a novel isoform, ATF3b, through the cAMP-response element/ATF site of the
      proglucagon gene promoter.
AB  - Glucagon, the second major glucose-regulated hormone in the control of glucose
      homeostasis, functions as a counter-regulator to insulin and is specifically
      produced by the pancreatic alpha cells. Its excessive biosynthesis and secretion
      is associated with diabetes mellitus. The expression of the proglucagon gene has
      been demonstrated to be regulated by a cAMP-dependent pathway through cAMP
      response element-binding protein (CREB) and possibly other transcription factors
      bound to its cAMP-response element (CRE)/activated transcription factor (ATF)
      site. Elsewhere we have shown that ATF3, a member of the ATF/CREB subfamily of
      the basic leucine zipper domain proteins, is expressed predominantly in the alpha
      cells of the pancreatic islets. In our attempts to further dissect the role of
      ATF3 proteins in alpha cells, we have identified and characterized a novel
      alternatively spliced form, ATF3b, and have compared the specific binding ability
      of ATF3 and ATF3b on the CRE/ATF motif of the proglucagon promoter. Our findings
      indicate the existence of a novel mechanism by which the transcription of the
      proglucagon gene is regulated in response to cAMP signals, in addition to CREB
      and in relation to glucose fluctuations in pancreatic alpha cells.

PMID- 12815048
TI  - Cloning, expression, and characterization of a human 4'-phosphopantetheinyl
      transferase with broad substrate specificity.
AB  - A single candidate 4'-phosphopantetheine transferase, identified by BLAST
      searches of the human genome sequence data base, has been cloned, expressed, and
      characterized. The human enzyme, which is expressed mainly in the cytosolic
      compartment in a wide range of tissues, is a 329-residue, monomeric protein. The
      enzyme is capable of transferring the 4'-phosphopantetheine moiety of coenzyme A
      to a conserved serine residue in both the acyl carrier protein domain of the
      human cytosolic multifunctional fatty acid synthase and the acyl carrier protein
      associated independently with human mitochondria. The human 4'-phosphopantetheine
      transferase is also capable of phosphopantetheinylation of peptidyl carrier and
      acyl carrier proteins from prokaryotes. The same human protein also has recently
      been implicated in phosphopantetheinylation of the alpha-aminoadipate
      semialdehyde dehydrogenase involved in lysine catabolism (Praphanphoj, V.,
      Sacksteder, K. A., Gould, S. J., Thomas, G. H., and Geraghty, M. T. (2001) Mol.
      Genet. Metab. 72, 336-342). Thus, in contrast to yeast, which utilizes separate
      4'-phosphopantetheine transferases to service each of three different carrier
      protein substrates, humans appear to utilize a single, broad specificity enzyme
      for all posttranslational 4'-phosphopantetheinylation reactions.

PMID- 12815049
TI  - MAHRP-1, a novel Plasmodium falciparum histidine-rich protein, binds
      ferriprotoporphyrin IX and localizes to the Maurer's clefts.
AB  - Using a stage-specific cDNA library from Plasmodium falciparum we have identified
      a gene coding for a novel histidine-rich protein (MAHRP-1). The gene is
      exclusively transcribed during early erythrocyte stages and codes for a small
      transmembrane protein. The C-terminal region contains a polymorphic stretch of
      histidine-rich repeats. Fluorescence microscopy studies using polyclonal mouse
      sera revealed that MAHRP-1 is located at the Maurer's clefts, which represent
      parasite-induced structures within the cytosol of infected erythrocytes.
      Biochemical studies showed that recombinant MAHRP-1 binds the toxic hemoglobin
      degradation product, ferriprotoporphyrin (FP) with a submicromolar dissociation
      constant and a stoichiometry determined by the number of DHGH motifs. The bound
      FP has increased peroxidase-like activity and is 10-fold more susceptible to H2O2
      induced degradation compared with unbound FP. These properties of MAHRP-1 suggest
      it may play a protective role against oxidative stress, and its location at the
      Maurer's clefts suggests a function in promoting the correct trafficking of
      exported proteins, such as P. falciparum erythrocyte membrane protein-1.

PMID- 12815050
TI  - The endocannabinoid system in human keratinocytes. Evidence that anandamide
      inhibits epidermal differentiation through CB1 receptor-dependent inhibition of
      protein kinase C, activation protein-1, and transglutaminase.
AB  - Anandamide (AEA), a prominent member of the endogenous ligands of cannabinoid
      receptors (endocannabinoids), is known to affect several functions of brain and
      peripheral tissues. A potential role for AEA in skin pathophysiology has been
      proposed, yet its molecular basis remains unknown. Here we report unprecedented
      evidence that spontaneously immortalized human keratinocytes (HaCaT) and normal
      human epidermal keratinocytes (NHEK) have the biochemical machinery to bind and
      metabolize AEA, i.e. a functional type-1 cannabinoid receptor (CB1R), a selective
      AEA membrane transporter (AMT), an AEA-degrading fatty acid amide hydrolase
      (FAAH), and an AEA-synthesizing phospholipase D (PLD). We show that, unlike CB1R
      and PLD, the activity of AMT and the activity and expression of FAAH increase
      while the endogenous levels of AEA decrease in HaCaT and NHEK cells induced to
      differentiate in vitro by 12-O-tetradecanoylphorbol 13-acetate (TPA) plus
      calcium. We also show that exogenous AEA inhibits the formation of cornified
      envelopes, a hallmark of keratinocyte differentiation, in HaCaT and NHEK cells
      treated with TPA plus calcium, through a CB1R-dependent reduction of
      transglutaminase and protein kinase C activity. Moreover, transient expression in
      HaCaT cells of the chloramphenicol acetyltransferase reporter gene under control
      of the loricrin promoter, which contained a wild-type or mutated activating
      protein-1 (AP-1) site, showed that AEA inhibited AP-1 in a CB1R-dependent manner.
      Taken together, these data demonstrate that human keratinocytes partake in the
      peripheral endocannabinoid system and show a novel signaling mechanism of CB1
      receptors, which may have important implications in epidermal differentiation and
      skin development.

PMID- 12815051
TI  - Expansion of polyglutamine induces the formation of quasi-aggregate in the early
      stage of protein fibrillization.
AB  - We examined the effects of the expansion of glutamine repeats on the early stage
      of protein fibrillization. Small-angle x-ray scattering (SAXS) and electron
      microscopic studies revealed that the elongation of polyglutamine from 35 to 50
      repeats in protein induced a large assembly of the protein upon incubation at 37
      degrees C and that its formation was completed in approximately 3 h. A bead
      modeling procedure based on SAXS spectra indicated that the largely assembled
      species of the protein, quasi-aggregate, is composed of 80 to approximately 90
      monomers and a bowl-like structure with long and short axes of 400 and 190 A,
      respectively. Contrary to fibril, the quasi-aggregate did not show a peak at S =
      0.21 A-1 corresponding to the 4.8-A spacing of beta-pleated sheets in SAXS
      spectra, and reacted with a monoclonal antibody specific to expanded
      polyglutamine. These results imply that beta-sheets of expanded polyglutamines in
      the quasi-aggregate are not orderly aligned and are partially exposed, in
      contrast to regularly oriented and buried beta-pleated sheets in fibril. The
      formation of non-fibrillary quasi-aggregate in the early phase of fibril
      formation would be one of the major characteristics of the protein containing an
      expanded polyglutamine.

PMID- 12815052
TI  - Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in
      leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3
      (FLT3).
AB  - The receptor tyrosine kinase FLT3 is constitutively activated by an internal
      tandem duplication (ITD) mutation within the juxtamembrane domain in 20-30% of
      patients with acute myeloid leukemia. In this study, we identified GTP-14564 as a
      specific kinase inhibitor for ITD-FLT3 and investigated the molecular basis of
      its specificity. GTP-14564 inhibited the growth of interleukin-3-independent
      Ba/F3 expressing ITD-FLT3 at 1 microM, whereas a 30-fold higher concentration of
      GTP-14564 was required to inhibit FLT3 ligand-dependent growth of Ba/F3
      expressing wild type FLT3 (wt-FLT3). However, this inhibitor suppressed the
      kinase activities of wt-FLT3 and ITD-FLT3 equally, suggesting that the signaling
      pathways for proliferation differ between wt-FLT3 and ITD-FLT3. Analysis of
      downstream targets of FLT3 using GTP-14564 revealed STAT5 activation to be
      essential for growth signaling of ITD-FLT3. In contrast, wt-FLT3 appeared to
      mainly use the MAPK pathway rather than the STAT5 pathway to transmit a
      proliferative signal. Further analysis demonstrated that the first two tyrosines
      in an ITD were critical for STAT5 activation and growth induction but that all of
      the tyrosines in the juxtamembrane region were dispensable in terms of the
      proliferation signals of wt-FLT3. These results indicate that an ITD mutation in
      FLT3 elicits an aberrant STAT5 activation that results in increased sensitivity
      to GTP-14564. Thus, FLT3-targeted inhibition is an attractive approach, with the
      potential for selective cytotoxicity, to the treatment of ITD-FLT3-positive acute
      myeloid leukemia.

PMID- 12815053
TI  - M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with
      the dissociation of the BRCA2-P/CAF complex.
AB  - BRCA2 is a breast tumor susceptibility gene encoding a 390-kDa protein with
      functions in maintaining genomic stability and cell cycle progression. Evidence
      has been accumulated to support the concept that BRCA2 has a critical role in
      homologous recombination of DNA double-stranded breaks by interacting with RAD51.
      In addition, BRCA2 may have chromatin modifying activity through interaction with
      a histone acetyltransferase protein, p300/CBP-associated factor (P/CAF). To
      explore how the functions of BRCA2 may be regulated, the post-translational
      modifications of BRCA2 throughout the cell cycle were examined. We found that
      BRCA2 is hyperphosphorylated specifically in M phase and becomes dephosphorylated
      as cells exit M phase and enter interphase. This specific phosphorylation of
      BRCA2 was not observed in cells treated with DNA-damaging agents. Systematic
      mapping of the potential mitosis specific phosphorylation sites revealed the N
      terminal 284 amino acids of BRCA2 (BR-N1) as the major region of phosphorylation
      and mass spectrometric analysis identified two phosphopeptides that contain
      "phosphorylation consensus motifs" for Polo-like kinase 1 (Plk1). Phosphorylation
      of BR-N1 with Plk1 recapitulated the electrophoretic mobility change as seen in
      BR-N1 isolated from M phase cells. Plk1 interacts with BRCA2 in vivo, and
      mutation of Ser193, Ser205/206, and Thr203/207 to Ala in BR-N1 abolished Plk1
      phosphorylation, suggesting that BRCA2 is the substrate of Plk1. Furthermore,
      both the hyperphosphorylated and hypophosphorylated forms of BRCA2 bind to RAD51,
      whereas the M phase hyperphosphorylated form of BRCA2 no longer associates with
      the P/CAF, suggesting that the dissociation of P/CAF-BRCA2 complex is regulated
      by phosphorylation. Taken together, these results implicate a potential role of
      BRCA2 in modulating M phase progression.

PMID- 12815054
TI  - BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the
      BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression.
AB  - Intramuscular injection of BMP-2 induces ectopic bone formation in vivo.
      Similarly, BMP-2 treatment blocks myogenic differentiation and induces
      osteoblastic transdifferentiation of premyoblastic C2C12 cells. Previous reports
      suggested that BMP-2-stimulated Runx2 expression could play a pivotal role in
      transdifferentiation. However, increased Runx2 expression by TGF-beta 1 did not
      support osteoblast differentiation in vitro. These results indicate that the
      induction of Runx2 is not sufficient to explain the BMP-induced
      transdifferentiation. We found that Dlx5 is specifically expressed in osteogenic
      cells, and is specifically induced by BMP-2 or -4 signaling but not by other
      osteotrophic signals or other TGF-beta superfamily members. Cycloheximide
      treatment indicated that Dlx5 was immediately induced by BMP signaling, while
      Runx2 required de novo protein synthesis. In addition, blocking or overexpressing
      each transcription factor indicated that Dlx5 is an indispensable mediator of BMP
      2-induced Runx2 expression but is not involved in TGF-beta 1-induced Runx2
      expression. Moreover, TGF-beta 1 opposed BMP-2-induced osteogenic
      transdifferentiation through Dlx5 suppression by de novo induction of AP-1. Taken
      together, these results indicate that Dlx5 is an indispensable regulator of BMP-2
      induced osteoblast differentiation as well as the counteraction point of the
      opposing TGF-beta 1 action.

PMID- 12815055
TI  - Characterization of a novel gastropod toxin (6-bromo-2-mercaptotryptamine) that
      inhibits shaker K channel activity.
AB  - A novel potassium channel antagonist has been purified from the defensive mucus
      secreted by Calliostoma canaliculatum, a marine snail found in the temperate
      coastal waters of the western Pacific. The toxin is expelled from the
      hypobranchial gland as part of a defensive response and is contained within a
      viscous matrix that minimizes dilution and degradation. The active compound was
      isolated by multistage microbore HPLC separations followed by bioactivity assays.
      Nuclear magnetic resonance, combined with electrospray ionization Fourier
      transform ion cyclotron resonance and electrospray ionization ion trap mass
      spectrometry indicate that the active component is a heretofore unknown indole
      derivative, a disulfide-linked dimer of 6-bromo-2-mercaptotryptamine (BrMT).
      Exudates from the hypobranchial glands of various marine mollusks have been
      sources for dye compounds such as 6-6 dibromoindigo, the ancient dye Tyrian
      purple. BrMT represents the first correlation of a hypobranchial gland exudate
      with a molecular response. Voltage clamp experiments with a number of K channel
      subtypes indicate that BrMT inhibits certain voltage-gated K channels of the Kv1
      subfamily.

PMID- 12815056
TI  - Positive and negative regulation of the gamma-secretase activity by nicastrin in
      a murine model.
AB  - Nicastrin is a component of the gamma-secretase complex that has been shown to
      adhere to presenilin-1 (PS1), Notch, and APP. Here we demonstrate that Nicastrin
      deficient mice showed a phenotype that is indistinguishable from PS1/PS2 double
      knock-out mice, whereas heterozygotes were healthy and viable. Fibroblasts
      derived from Nicastrin-deficient embryos were unable to generate amyloid beta
      peptide and failed to release the intracellular domain of APP- or Notch1-Gal4
      VP16 fusion proteins. Additionally, C- and N-terminal fragments of PS1 and the C
      terminal fragments of PS2 were not detectable in Nicastrin-null fibroblasts,
      whereas full-length PS1 accumulated in null fibroblasts, indicating that
      Nicastrin is required for the endoproteolytic processing of presenilins.
      Interestingly, cells derived from Nicastrin heterozygotes produced relatively
      higher levels of amyloid beta-peptide whether the source was endogenous mouse or
      transfected human APP. These data demonstrate that Nicastrin is essential for the
      gamma-secretase cleavage of APP and Notch in mammalian cells and that Nicastrin
      has both positive and negative functions in the regulation of gamma-secretase
      activity.

PMID- 12815057
TI  - Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is
      crucial for its function.
AB  - Mammalian Sprouty (Spry) proteins are now established as receptor tyrosine kinase
      induced modulators of the Ras/mitogen-activated protein kinase pathway.
      Specifically, hSpry2 inhibits the fibroblast growth factor receptor (FGFR)
      induced mitogen-activated protein kinase pathway but conversely prolongs activity
      of the same pathway following epidermal growth factor (EGF) stimulation, where
      activated EGF receptors are retained on the cell surface. In this study it is
      demonstrated that hSpry2 is tyrosine-phosphorylated upon stimulation by either
      FGFR or EGF and subsequently binds endogenous c-Cbl with high affinity. A
      conserved motif on hSpry2, together with phosphorylation on tyrosine 55, is
      required for its enhanced interaction with the SH2-like domain of c-Cbl. A hSpry2
      mutant (Y55F) that did not exhibit an enhanced binding with c-Cbl failed to
      retain EGF receptors on the cell surface. Furthermore, individually mutating
      hSpry2 residues 52-59 to alanine indicated a tight correlation between their
      affinity for c-Cbl binding and their inhibition of ERK2 activity in the FGFR
      pathway. We postulate that tyrosine phosphorylation "activates" hSpry2 by
      enhancing its interaction with c-Cbl and that this interaction is critical for
      its physiological function in a signal-specific context.

PMID- 12815058
TI  - Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra-
      and extracellular sphingosine-1-phosphate levels and cell viability.
AB  - Sphingosine-1-phosphate (S1P) is a highly bioactive lipid that exerts numerous
      biological effects both intracellularly as a second messenger and extracellularly
      by binding to its G-protein-coupled receptors of the endothelial differentiation
      gene family (S1P receptors-(1-5)). Intracellularly, at least two enzymes,
      sphingosine kinase and S1P phosphatase, regulate the activity of S1P by governing
      the phosphorylation status of S1P. To study the regulation of S1P levels, we
      cloned the human isoform of S1P phosphatase 1 (hSPPase1). The hSPPase1 has 78%
      homology to the mouse SPPase at the amino acid level with 6-8 possible
      transmembrane domains. Confocal microscopy revealed green fluorescent protein
      tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to
      endoplasmic reticulum with calreticulin. According to Northern blot analysis,
      hSPPase1 is expressed in most tissues, with the strongest levels found in the
      highly vascular tissues of placenta and kidney. Transient overexpression of
      hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and
      dihydro-S1P, indicating that the expressed protein was functional. Small
      interfering RNA (siRNA) knockdown of endogenous hSPPase1 drastically reduced
      hSPPase1 mRNA levels, as confirmed by reverse transcription PCR, and resulted in
      an overall 25% reduction of in vitro phosphatase activity in the membrane
      fractions. Sphingolipid mass measurements in hSPPase1 siRNA knockdown cells
      revealed a 2-fold increase of S1P levels and concomitant decrease in sphingosine.
      In vivo labeling of hSPPase1 siRNA-treated cells showed accumulation of S1P
      within cells, as well as significantly increased secretion of S1P into the media,
      indicating that hSPPase1 regulates secreted S1P. In addition, siRNA-induced
      knockdown of hSPPase1 endowed resistance to tumor necrosis factor-alpha and the
      chemotherapeutic agent daunorubicin. Collectively, these data suggest that
      regulation of hSPPase1 with the resultant changes in cellular and secreted S1P
      could have important implications to cell proliferation, angiogenesis, and
      apoptosis.

PMID- 12815059
TI  - Purification and characterization of recombinant, human acid ceramidase.
      Catalytic reactions and interactions with acid sphingomyelinase.
AB  - Human acid ceramidase was overexpressed in Chinese hamster ovary cells by
      amplification of the transfected, full-length cDNA. The majority of the
      overexpressed enzyme was secreted into the culture media and purified to apparent
      homogeneity. The purified protein contained the same 13-(alpha) and 40 (beta)-kDa
      subunits as human acid ceramidase from natural sources, had an acidic pH optimum
      (4.5), and followed normal Michaelis-Menten kinetics using 14C- and BODIPY
      labeled C12-ceramide as substrates. Deglycosylation studies showed that the
      recombinant enzyme contained mostly "high mannose" type oligosaccharides and that
      two distinct beta-subunits were present. Amino acid sequencing of these subunit
      polypeptides revealed a single N terminus, suggesting that the approximately 2-4
      kDa molecular mass difference was likely due to C-terminal processing. The
      purified enzyme also catalyzed ceramide synthesis in vitro using 14C-labeled C12
      fatty acid and sphingosine as substrates. Surprisingly, we found that media from
      the overexpressing hamster cells had increased acid sphingomyelinase activity and
      that this activity could be co-precipitated with acid ceramidase using anti
      ceramidase antibodies. Overexpression of acid ceramidase in normal human skin
      fibroblasts also led to enhanced acid sphingomyelinase secretion, but this was
      not observed in Niemann-Pick disease cells. RNA studies showed that this
      increased activity was not due to overexpression of the endogenous acid
      sphingomyelinase gene. Uptake studies using mouse macrophages revealed rapid
      internalization of the acid ceramidase activity from the hamster cell media but
      not acid sphingomyelinase. These studies provide new insights into acid
      ceramidase and the related lipid hydrolase, acid sphingomyelinase.

PMID- 12815060
TI  - Membrane topology of Bves/Pop1A, a cell adhesion molecule that displays dynamic
      changes in cellular distribution during development.
AB  - We investigated the membrane topology of Bves/Pop1A as a foundation to dissect
      the molecular basis and function of Bves/Pop1A trafficking during development.
      Bves contains two asparagine-linked glycosylation sites within the amino terminus
      and three putative membrane domains. Therefore, glycosylation assays were
      performed to determine if the amino terminus of Bves is delivered into the
      endoplasmic reticulum lumen and glycosylated. We establish that Bves from chick
      heart and transfected cells is glycosylated, implying that the amino terminus of
      cell surface molecules is extracellular. Three biochemically distinct approaches
      were utilized to determine the orientation of the carboxyl terminus of Bves.
      First, glycosylation of Bves at exogenous sites within the carboxyl terminus was
      only observed in a construct that lacked the third membrane domain, which
      presumably reversed the orientation of the carboxyl terminus. Second, co
      expression of full-length Bves with soluble, carboxyl-terminal Bves constructs
      that reside in different subcellular compartments revealed that Bves-Bves
      interactions occur in the cytoplasm. Third, the immunoreactivity of endogenous
      Bves at the cell surface of epicardial cells was dramatically enhanced with
      detergent. These results suggest that the membrane topology of cell surface
      Bves/Pop1A is composed of an extracellular amino terminus, three transmembrane
      domains, and a cytoplasmic carboxyl terminus. We therefore hypothesize that the
      carboxyl terminus regulates the cellular distribution of Bves/Pop1A during
      coronary vessel development.

PMID- 12815061
TI  - Rapid suppression of mitochondrial permeability transition by methylglyoxal. Role
      of reversible arginine modification.
AB  - Methylglyoxal (MG) (pyruvaldehyde) is a reactive carbonyl compound produced in
      glycolysis. MG can form covalent adducts on proteins resulting in advanced
      glycation end products that may alter protein function. Here we report that MG
      covalently modifies the mitochondrial permeability transition pore (PTP), a high
      conductance channel involved in the signal transduction of cell death processes.
      Incubation of isolated mitochondria with MG for a short period of time (5 min),
      followed by removal of excess free MG, prevented both ganglioside GD3- and Ca2+
      induced PTP opening and the ensuing membrane depolarization, swelling, and
      cytochrome c release. Under these conditions MG did not significantly interfere
      with mitochondrial substrate transport, respiration, or oxidative
      phosphorylation. The suppression of permeability transition was reversible
      following extended incubation in MG-free medium. Of the 29 physiological carbonyl
      and dicarbonyl compounds tested only MG and its analogue glyoxal were able to
      specifically alter the behavior of the PTP. Using a set of arginine-containing
      peptides, we found that the major MG-derived arginine adduct formed, following a
      short time exposure to MG, was the 5-hydro-5-methylimidazol-4-one derivative.
      These findings demonstrate that MG rapidly modifies the PTP covalently and
      stabilizes the PTP in the closed conformation. This is probably due to the
      formation of an imidazolone adduct on an arginine residue involved in the control
      of PTP conformation (Linder, M. D., Morkunaite-Haimi, S., Kinnunen, P. J. K.,
      Bernardi, P., and Eriksson, O. (2002) J. Biol. Chem. 277, 937-942). We deduce
      that the permeability transition constitutes a potentially important
      physiological target of MG.

PMID- 12815062
TI  - Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by
      low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK
      activity.
AB  - Protein tyrosine phosphorylation is one of the earliest signaling events detected
      in response to lymphocyte function-associated antigen-1 (LFA-1) engagement during
      lymphocyte adhesion. In particular, the focal adhesion kinase p125FAK, involved
      in the modulation and rearrangement of the actin cytoskeleton, seems to be a
      crucial mediator of LFA-1 signaling. Herein, we investigate the role of a FAK
      tyrosine phosphatase, namely low molecular weight phosphotyrosine phosphatase
      (LMW-PTP), in the modulation of LFA-1-mediated T cell adhesion. Overexpression of
      LMW-PTP in Jurkat cells revealed an impairment of LFA-1-dependent cell-cell
      adhesion upon T cell receptor (TCR) stimulation. Moreover, in these conditions
      LMW-PTP causes FAK dephosphorylation, thus preventing the activation of FAK
      downstream pathways. Our results also demonstrated that, upon antigen
      stimulation, LMW-PTP-dependent FAK inhibition is associated to a strong reduction
      of LFA-1 and TCR co-clustering toward a single region of T cell surface, thus
      causing an impairment of receptor activity by preventing changes in their avidity
      state. Because co-localization of both LFA-1 and TCR is an essential event during
      encounters of T cells with antigen-presenting cells and immunological synapse
      (IS) formation, we suggest an intriguing role of LMW-PTP in IS establishment and
      stabilization through the negative control of FAK activity and, in turn, of cell
      surface receptor redistribution.

PMID- 12815063
TI  - Fibroblast growth factor (FGF) homologous factors share structural but not
      functional homology with FGFs.
AB  - Fibroblast growth factors (FGFs) interact with heparan sulfate glycosaminoglycans
      and the extracellular domains of FGF cell surface receptors (FGFRs) to trigger
      receptor activation and biological responses. FGF homologous factors (FHF1-FHF4;
      also known as FGF11-FGF14) are related to FGFs by substantial sequence homology,
      yet their only documented interactions are with an intracellular kinase scaffold
      protein, islet brain-2 (IB2) and with voltage-gated sodium channels. In this
      report, we show that recombinant FHFs can bind heparin with high affinity like
      classical FGFs yet fail to activate any of the seven principal FGFRs. Instead, we
      demonstrate that FHFs bind IB2 directly, furthering the contention that FHFs and
      FGFs elicit their biological effects by binding to different protein partners. To
      understand the molecular basis for this differential target binding specificity,
      we elucidated the crystal structure of FHF1b to 1.7-A resolution. The FHF1b core
      domain assumes a beta-trefoil fold consisting of 12 antiparallel beta strands
      (beta 1 through beta 12). The FHF1b beta-trefoil core is remarkably similar to
      that of classical FGFs and exhibits an FGF-characteristic heparin-binding surface
      as attested to by the number of bound sulfate ions. Using molecular modeling and
      structure-based mutational analysis, we identified two surface residues, Arg52 in
      the beta 4-beta 5 loop and Val95 in the beta 9 strand of FHF1b that are required
      for the interaction of FHF1b with IB2. These two residues are unique to FHFs, and
      mutations of the corresponding residues of FGF1 to Arg and Val diminish the
      capacity of FGF1 to activate FGFRs, suggesting that these two FHF residues
      contribute to the inability of FHFs to activate FGFRs. Hence, FHFs and FGFs bear
      striking structural similarity but have diverged to direct related surfaces
      toward interaction with distinct protein targets.

PMID- 12815064
TI  - The caspase-like sites of proteasomes, their substrate specificity, new
      inhibitors and substrates, and allosteric interactions with the trypsin-like
      sites.
AB  - Proteasomes are the primary sites for protein degradation in mammalian cells.
      Each proteasome particle contains two chymotrypsin-like, two trypsin-like, and
      two caspase-like proteolytic sites. Previous studies suggest a complex network of
      allosteric interactions between these catalytic and multiple regulatory sites. We
      used positional scanning combinatorial substrate libraries to determine the
      extended substrate specificity of the caspase-like sites. Based on this analysis,
      several new substrates were synthesized, the use of which confirmed earlier
      observations that caspase-like sites (often termed postglutamyl peptide
      hydrolase) cleave after aspartates better than after glutamates. Highly selective
      inhibitors of the caspase-like sites were also generated. They stimulated trypsin
      like activity of yeast 20 S proteasomes up to 3-fold but not when binding of the
      inhibitor to the caspase-like sites was prevented in a mutant carrying an
      uncleaved propeptide. Although substrates of the caspase-like sites
      allosterically inhibit the chymotrypsin-like activity, inhibitors of the caspase
      like sites do not affect the chymotrypsin-like sites. Furthermore, when caspase
      like sites were occupied by the uncleaved propeptide or inhibitor, their
      substrates still inhibited the chymotrypsin-like activity. Thus, occupancy of the
      caspase-like sites stimulates the trypsin-like activity of proteasomes, but
      substrates of the caspase-like sites inhibit the chymotrypsin-like activity by
      binding to a distinct noncatalytic site.

PMID- 12815065
TI  - Multiple roles of ephrins in morphogenesis, neuronal networking, and brain
      function.

PMID- 12815066
TI  - Regulated CPEB phosphorylation during meiotic progression suggests a mechanism
      for temporal control of maternal mRNA translation.
AB  - CPEB is an mRNA-binding protein that stimulates polyadenylation-induced
      translation of maternal mRNA once it is phosphorylated on Ser 174 or Thr 171
      (species-dependent). Disruption of the CPEB gene in mice causes an arrest of
      oogenesis at embryonic day 16.5 (E16.5), when most oocytes are in pachytene of
      prophase I. Here, we show that CPEB undergoes Thr 171 phosphorylation at E16.5,
      but dephosphorylation at the E18.5, when most oocytes are entering diplotene.
      Although phosphorylation is mediated by the kinase aurora, the dephosphorylation
      is due to the phosphatase PP1. The temporal control of CPEB phosphorylation
      suggests a mechanism in which CPE-containing mRNA translation is stimulated at
      pachytene and metaphase I.

PMID- 12815067
TI  - Aberrant histone acetylation, altered transcription, and retinal degeneration in
      a Drosophila model of polyglutamine disease are rescued by CREB-binding protein.
AB  - Sequestration of the transcriptional coactivator CREB-binding protein (CBP), a
      histone acetyltransferase, has been implicated in the pathogenesis of
      polyglutamine expansion neurodegenerative disease. We used a Drosophila model to
      demonstrate that polyglutamine-induced neurodegeneration is accompanied by a
      defect in histone acetylation and a substantial alteration in the transcription
      profile. Furthermore, we demonstrate complete functional and morphological rescue
      by up-regulation of endogenous Drosophila CBP (dCBP). Rescue of the degenerative
      phenotype is associated with eradication of polyglutamine aggregates, recovery of
      histone acetylation, and normalization of the transcription profile. These
      findings suggest that histone acetylation is an early target of polyglutamine
      toxicity and indicate that transcriptional dysregulation is an important part of
      the pathogenesis of polyglutamine-induced neurodegeneration.

PMID- 12815068
TI  - MAX4 and RMS1 are orthologous dioxygenase-like genes that regulate shoot
      branching in Arabidopsis and pea.
AB  - Shoot branching is inhibited by auxin transported down the stem from the shoot
      apex. Auxin does not accumulate in inhibited buds and so must act indirectly. We
      show that mutations in the MAX4 gene of Arabidopsis result in increased and auxin
      resistant bud growth. Increased branching in max4 shoots is restored to wild type
      by grafting to wild-type rootstocks, suggesting that MAX4 is required to produce
      a mobile branch-inhibiting signal, acting downstream of auxin. A similar role has
      been proposed for the pea gene, RMS1. Accordingly, MAX4 and RMS1 were found to
      encode orthologous, auxin-inducible members of the polyene dioxygenase family.

PMID- 12815069
TI  - Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly
      inactivates IAPs and facilitates caspase activity in apoptosis.
AB  - Omi/HtrA2 is a mitochondrial serine protease that is released into the cytosol
      during apoptosis to antagonize inhibitors of apoptosis (IAPs) and contribute to
      caspase-independent cell death. Here, we demonstrate that Omi/HtrA2 directly
      cleaves various IAPs in vitro, and the cleavage efficiency is determined by its
      IAP-binding motif, AVPS. Cleavage of IAPs such as c-IAP1 substantially reduces
      its ability to inhibit and ubiquitylate caspases. In contrast to the
      stoichiometric anti-IAP activity by Smac/DIABLO, Omi/HtrA2 cleavage of c-IAP1 is
      catalytic and irreversible, thereby more efficiently inactivating IAPs and
      promoting caspase activity. Elimination of endogenous Omi by RNA interference
      abolishes c-IAP1 cleavage and desensitizes cells to apoptosis induced by TRAIL.
      In addition, overexpression of cleavage-site mutant c-IAP1 makes cells more
      resistant to TRAIL-induced caspase activation. This IAP cleavage by Omi is
      independent of caspase. Taken together, these results indicate that unlike
      Smac/DIABLO, Omi/HtrA2's catalytic cleavage of IAPs is a key mechanism for it to
      irreversibly inactivate IAPs and promote apoptosis.

PMID- 12815070
TI  - Physical and functional interactions between polo kinase and the spindle pole
      component Cut12 regulate mitotic commitment in S. pombe.
AB  - Commitment to mitosis is regulated by a protein kinase complex called MPF. MPF is
      inhibited by Wee1-related kinases and activated by Cdc25 phosphatase. MPF
      activation further boosts Cdc25 and represses Wee1. This feedback control
      probably involves polo kinase. A dominant cut12.s11 mutation in the
      Schizosaccharomyces pombe spindle pole body (SPB) component Cut12 both suppresses
      the conditional lethal mitotic commitment defect of cdc25.22 and promotes
      premature association of the S. pombe polo kinase, Plo1, with the SPB. We now
      show that Cut12 associated with Plo1 in two hybrid and immunoprecipitation
      assays. Plo1 function was required for recognition of the mitotic SPB by the
      phospho-specific antibody MPM-2. In vivo MPM-2 staining and in vitro kinase
      assays established that the loss-of-function mutation, cut12.1, reduced mitotic
      activation of Plo1, whereas the gain-of-function mutation, cut12.s11, promoted
      higher levels of Plo1 activity than were normally seen in interphase. cut12.s11
      could not promote mitotic commitment of cdc25.22 cells when Plo1 function was
      compromised. Expression of a constitutively active plo1 allele suppressed the
      mitotic commitment defect of cdc25.22. These data suggest that cut12.s11
      suppresses cdc25.22 by promoting Plo1 activity. Furthermore, the delayed mitotic
      commitment of plo1.ts2 cells suggests that Plo1 is an integral part of the core
      controls that modulate MPF activation in S. pombe.

PMID- 12815071
TI  - The Polycomb-group protein MEDEA regulates seed development by controlling
      expression of the MADS-box gene PHERES1.
AB  - The Polycomb-group (PcG) proteins MEDEA, FERTILIZATION INDEPENDENT ENDOSPERM, and
      FERTILIZATION INDEPENDENT SEED2 regulate seed development in Arabidopsis by
      controlling embryo and endosperm proliferation. All three of these FIS-class
      proteins are likely subunits of a multiprotein PcG complex, which epigenetically
      regulates downstream target genes that were previously unknown. Here we show that
      the MADS-box gene PHERES1 (PHE1) is commonly deregulated in the fis-class
      mutants. PHE1 belongs to the evolutionarily ancient type I class of MADS-box
      proteins that have not yet been assigned any function in plants. Both MEDEA and
      FIE directly associate with the promoter region of PHE1, suggesting that PHE1
      expression is epigenetically regulated by PcG proteins. PHE1 is expressed
      transiently after fertilization in both the embryo and the endosperm; however, it
      remains up-regulated in the fis mutants, consistent with the proposed function of
      the FIS genes as transcriptional repressors. Reduced expression levels of PHE1 in
      medea mutant seeds can suppress medea seed abortion, indicating a key role of
      PHE1 repression in seed development. PHE1 expression in a hypomethylated medea
      mutant background resembles the wild-type expression pattern and is associated
      with rescue of the medea seed-abortion phenotype. In summary, our results
      demonstrate that seed abortion in the medea mutant is largely mediated by
      deregulated expression of the type I MADS-box gene PHE1.

PMID- 12815072
TI  - Definition of a novel growth factor-dependent signal cascade for the suppression
      of bile acid biosynthesis.
AB  - The nuclear bile acid receptor FXR has been proposed to play a central role in
      the feedback repression of the gene encoding cholesterol 7 alpha-hydroxylase
      (CYP7A1), the first and rate-limiting step in the biosynthesis of bile acids. We
      demonstrate that FXR directly regulates expression of fibroblast growth factor-19
      (FGF-19), a secreted growth factor that signals through the FGFR4 cell-surface
      receptor tyrosine kinase. In turn, FGF-19 strongly suppresses expression of
      CYP7A1 in primary cultures of human hepatocytes and mouse liver through a c-Jun N
      terminal kinase (JNK)-dependent pathway. This signaling cascade defines a novel
      mechanism for feedback repression of bile acid biosynthesis and underscores the
      vital role of FXR in the regulation of multiple pathways of cholesterol
      catabolism in the liver.

PMID- 12815073
TI  - Drosophila FACT contributes to Hox gene expression through physical and
      functional interactions with GAGA factor.
AB  - Chromatin structure plays a critical role in the regulation of transcription.
      Drosophila GAGA factor directs chromatin remodeling to its binding sites. We show
      here that Drosophila FACT (facilitates chromatin transcription), a heterodimer of
      dSPT16 and dSSRP1, is associated with GAGA factor through its dSSRP1 subunit,
      binds to a nucleosome, and facilitates GAGA factor-directed chromatin remodeling.
      Moreover, genetic interactions between Trithorax-like encoding GAGA factor and
      spt16 implicate the GAGA factor-FACT complex in expression of Hox genes
      Ultrabithorax, Sex combs reduced, and Abdominal-B. Chromatin immunoprecipitation
      experiments indicated the presence of the GAGA factor-FACT complex in the
      regulatory regions of Ultrabithorax and Abdominal-B. These data illustrate a
      crucial role of FACT in the modulation of chromatin structure for the regulation
      of gene expression.

PMID- 12815074
TI  - A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent
      stabilization of xeroderma pigmentosum group C protein.
AB  - Primary DNA damage sensing in mammalian global genome nucleotide excision repair
      (GG-NER) is performed by the xeroderma pigmentosum group C (XPC)/HR23B protein
      complex. HR23B and HR23A are human homologs of the yeast ubiquitin-domain repair
      factor RAD23, the function of which is unknown. Knockout mice revealed that
      mHR23A and mHR23B have a fully redundant role in NER, and a partially redundant
      function in embryonic development. Inactivation of both genes causes embryonic
      lethality, but appeared still compatible with cellular viability. Analysis of
      mHR23A/B double-mutant cells showed that HR23 proteins function in NER by
      governing XPC stability via partial protection against proteasomal degradation.
      Interestingly, NER-type DNA damage further stabilizes XPC and thereby enhances
      repair. These findings resolve the primary function of RAD23 in repair and reveal
      a novel DNA-damage-dependent regulation mechanism of DNA repair in eukaryotes,
      which may be part of a more global damage-response circuitry.

PMID- 12815075
TI  - Unequal treatment: the Institute of Medicine report and its public health
      implications.

PMID- 12815076
TI  - Defining cultural competence: a practical framework for addressing racial/ethnic
      disparities in health and health care.
AB  - OBJECTIVES: Racial/ethnic disparities in health in the U.S. have been well
      described. The field of "cultural competence" has emerged as one strategy to
      address these disparities. Based on a review of the relevant literature, the
      authors develop a definition of cultural competence, identify key components for
      intervention, and describe a practical framework for implementation of measures
      to address racial/ethnic disparities in health and health care. METHODS: The
      authors conducted a literature review of academic, foundation, and government
      publications focusing on sociocultural barriers to care, the level of the health
      care system at which a given barrier occurs, and cultural competence efforts that
      address these barriers. RESULTS: Sociocultural barriers to care were identified
      at the organizational (leadership/workforce), structural (processes of care), and
      clinical (provider-patient encounter) levels. A framework of cultural competence
      interventions--including minority recruitment into the health professions,
      development of interpreter services and language-appropriate health educational
      materials, and provider education on cross-cultural issues--emerged to categorize
      strategies to address racial/ethnic disparities in health and health care.
      CONCLUSIONS: Demographic changes anticipated over the next decade magnify the
      importance of addressing racial/ethnic disparities in health and health care. A
      framework of organizational, structural, and clinical cultural competence
      interventions can facilitate the elimination of these disparities and improve
      care for all Americans.

PMID- 12815077
TI  - The human face of health disparities.
AB  - In the last 20 years, the issue of disparities in health between racial/ethnic
      groups has moved from the realm of common sense and anecdote to the realm of
      science. Hard, cold data now force us to consider what many had long taken for
      granted. Not only does health differ by race/ethnicity, but our health care
      system itself is deeply biased. From lack of diversity in the leadership and
      workforce, to ethnocentric systems of care, to biased clinical decision-making,
      the American health care system is geared to treat the majority, while the
      minority suffers. The photos shown here are of patients and scenes that recall
      some of the important landmarks in research on racial/ethnic disparities in
      health. The purpose is to put faces and humanity onto the numbers. While we now
      have great bodies of evidence upon which to lobby for change, in the end, each
      statistic still represents a personal tragedy or an individual triumph.

PMID- 12815078
TI  - Reducing diabetes health disparities through community-based participatory action
      research: the Chicago Southeast Diabetes Community Action Coalition.
AB  - To address disproportionately high rates of diabetes morbidity and mortality in
      some of Chicago's medically underserved minority neighborhoods, a group of
      community residents, medical and social service providers, and a local university
      founded the Chicago Southeast Diabetes Community Action Coalition, a Centers for
      Disease Control and Prevention REACH 2010 Initiative. A community-based
      participatory action research model guided coalition activities from
      conceptualization through implementation. Capacity building activities included
      training on: diabetes, coalition building, research methods, and action planning.
      Other activities sought to increase coalition members' understanding of the
      social causes and potential solutions for health disparities related to diabetes.
      Trained coalition members conducted epidemiologic analyses, focus groups, a
      telephone survey, and a community inventory. All coalition members participated
      in decisions. The participatory process led to increased awareness of the
      complexities of diabetes in the community and to a state of readiness for social
      action. Data documented disparities in diabetes. The participatory action
      research approach (a) encouraged key stakeholders outside of the health care
      sector to participate (e.g., business sector, church groups); (b) permitted an
      examination of the sociopolitical context affecting the health of the community;
      (c) provided an opportunity to focus on preventing the onset of diabetes and its
      complications; (d) increased understanding of the importance of community
      research in catalyzing social action aimed at community and systems change and
      change among change agents.

PMID- 12815079
TI  - A partnership to reduce African American infant mortality in Genesee County,
      Michigan.
AB  - A partnership in Genesee County, Michigan, has been working to reduce African
      American infant mortality. A plan was developed utilizing "bench" science and
      community residents' "trench" knowledge. Its theoretical foundation is
      ecological, grounded in a philosophy of public health as social justice, and
      based on the understanding that cultural beliefs and practices can be both
      protective and harmful. Partners agree that no single intervention will eliminate
      racial disparities and that interventions must precede, include, and follow the
      period of pregnancy. Core themes for the work include: reducing racism, enhancing
      the medical care and social services systems, and fostering community
      mobilization. Strategies include community dialogue and raising awareness,
      education and training, outreach and advocacy, and mentoring and support. The
      evaluation has several components: scrutinizing the effect of partnership
      activities on direct measures of infant health; analyzing changes in knowledge,
      attitudes, behaviors and other mediating variables thought to influence maternal
      and infant health; and effecting changes in personal and organizational policy
      and practice.

PMID- 12815080
TI  - Black-white infant mortality disparity in the United States: a societal litmus
      test. Commentary on "A partnership to reduce African American infant mortality in
      Genesee County, Michigan".

PMID- 12815081
TI  - A community approach to addressing excess breast and cervical cancer mortality
      among women of African descent in Boston.
AB  - In 2000, the REACH Boston 2010 Breast and Cervical Cancer Coalition conducted a
      community needs assessment and found several factors that may have contributed to
      disproportionately high breast and cervical cancer mortality among black women:
      (a) Focus group participants reported that many women in their communities had
      limited awareness about risk factors for cancer as well as about screening. (b)
      Black women experienced barriers to care related to the cultural competence of
      providers and of institutions. (c) Black women were not receiving adequate follow
      up for abnormal mammograms and Pap smears. The Coalition's Community Action Plan
      to address disparities includes a model primary care service for black women;
      scholarships to increase the number of black mammogram technologists; primary
      care provider and radiology technologist training about disparities and cultural
      competence; and education to increase awareness among black women and to increase
      leadership and advocacy skills.

PMID- 12815082
TI  - The complexity of finding solutions to reducing racial/ethnic disparities in
      health care outcomes. Commentary on "A community approach to addressing excess
      breast and cervical cancer mortality among women of African descent in Boston".

PMID- 12815083
TI  - Teaching physicians-in-training to address racial disparities in health: a
      hospital-community partnership.
AB  - Racial and ethnic disparities in health care continue to be a major impediment to
      improving the health of many communities in the United States. Efforts must be
      directed at the multiple social, economic, and historic determinants of health
      disparities. In addition, health care providers must be aware of these
      determinants and must have the tools to address them in their individual
      relationships with patients. This article describes a partnership that arose out
      of the mutual recognition by a community organization and public hospital of the
      need to (a) teach physicians how to recognize the root causes of health
      disparities, (b) improve their cross-cultural understanding and communication,
      and (c) enhance their awareness of the capacity of community resources to
      positively impact their patients' lives.

PMID- 12815084
TI  - Community-physician education partnerships: one strategy to eliminate
      racial/ethnic health disparities. Commentary on "Teaching physicians-in-training
      to address racial disparities in health: a hospital-community partnership".

PMID- 12815086
TI  - Examining African Americans' mistrust of the health care system: expanding the
      research question. Commentary on "Race and trust in the health care system".

PMID- 12815085
TI  - Race and trust in the health care system.
AB  - OBJECTIVE: A legacy of racial discrimination in medical research and the health
      care system has been linked to a low level of trust in medical research and
      medical care among African Americans. While racial differences in trust in
      physicians have been demonstrated, little is known about racial variation in
      trust of health insurance plans and hospitals. For the present study, the authors
      analyzed responses to a cross-sectional telephone survey to assess the
      independent relationship of self-reported race (non-Hispanic black or non
      Hispanic white) with trust in physicians, hospitals, and health insurance plans.
      METHODS: Respondents ages 18-75 years were asked to rate their level of trust in
      physicians, health insurance plans, and hospitals. Items from the Medical
      Mistrust Index were used to assess fear and suspicion of hospitals. RESULTS:
      Responses were analyzed for 49 (42%) non-Hispanic black and 69 (58%) non-Hispanic
      white respondents (N=118; 94% of total survey population). A majority of
      respondents trusted physicians (71%) and hospitals (70%), but fewer trusted their
      health insurance plans (28%). After adjustment for potential confounders, non
      Hispanic black respondents were less likely to trust their physicians than non
      Hispanic white respondents (adjusted absolute difference 37%; p=0.01) and more
      likely to trust their health insurance plans (adjusted absolute difference 28%;
      p=0.04). The difference in trust of hospitals (adjusted absolute difference 13%)
      was not statistically significant. Non-Hispanic black respondents were more
      likely than non-Hispanic white respondents to be concerned about personal privacy
      and the potential for harmful experimentation in hospitals. CONCLUSIONS: Patterns
      of trust in components of our health care system differ by race. Differences in
      trust may reflect divergent cultural experiences of blacks and whites as well as
      differences in expectations for care. Improved understanding of these factors is
      needed if efforts to enhance patient access to and satisfaction with care are to
      be effective.

PMID- 12815087
TI  - Breastfeeding advice given to African American and white women by physicians and
      WIC counselors.
AB  - OBJECTIVE: This study determined rates of breastfeeding advice given to African
      American and white women by medical providers and WIC nutrition counselors, and
      sought to determine whether racial differences in advice contributed to racial
      differences in rates of breastfeeding. METHODS: The study used data from the 1988
      National Maternal and Infant Health Survey, a cross-sectional survey of a
      nationally representative sample of mothers with a live birth, infant death, or
      fetal death in 1988. The authors compared white women (n=3,966) and African
      American women (n=4,791) with a live birth in 1988 on self-reported rates of
      medical provider and WIC advice to breastfeed, WIC advice to bottlefeed, and
      breastfeeding. RESULTS: Self-reported racial identification did not predict
      medical provider advice. However, being African American was associated with less
      likelihood of breastfeeding advice and greater likelihood of bottlefeeding advice
      from WIC nutrition counselors. In multivariate analyses controlling for
      differences in advice, being African American was independently associated with
      lower breastfeeding rates (odds ratio [OR] = 0.41, 95% CI 0.32, 0.52).
      CONCLUSIONS: African American women were less likely than white women to report
      having received breastfeeding advice from WIC counselors and more likely to
      report having received bottlefeeding advice from WIC counselors. However, African
      American and white women were equally likely to report having received
      breastfeeding advice from medical providers. Lower rates of breastfeeding advice
      from medical or nutritional professionals do not account for lower rates of
      breastfeeding among African American women.

PMID- 12815088
TI  - A closer look at racial/ethnic disparities in breastfeeding. Commentary on
      "Breastfeeding advice given to African American and white women by physicians and
      WIC counselors".

PMID- 12815090
TI  - TV sex becoming safer.

PMID- 12815089
TI  - "Megan's laws" and the US Constitution: implications for public health policy and
      practice.

PMID- 12815092
TI  - Implementing community-campus partnerships in South Carolina: collaborative
      efforts to improve public health.

PMID- 12815093
TI  - The RNA-protein complex: direct probing of the interfacial recognition dynamics
      and its correlation with biological functions.
AB  - The N protein from bacteriophage lambda is a key regulator of transcription
      antitermination. It specifically recognizes a nascent mRNA stem loop termed boxB,
      enabling RNA polymerase to read through downstream terminators processively. The
      stacking interaction between Trp-18 of WT N protein and A7 of boxB RNA is crucial
      for efficient antitermination. Here, we report on the direct probing of the
      dynamics for this interfacial binding and the correlation of the dynamics with
      biological functions. Specifically, we examined the influence of structural
      changes in four peptides on the femtosecond dynamics of boxB RNA (2-aminopurine
      labeled in different positions), through mutations of critical residues of N
      peptide (residues 1-22). We then compare their in vivo (Escherichia coli)
      transcription antitermination activities with the dynamics. The results
      demonstrate that the RNA-peptide complexes adopt essentially two dynamical
      conformations with the time scale for interfacial interaction in the two
      structures being vastly different, 1 ps for the stacked structure and nanosecond
      for the unstacked one; only the weighted average of the two is detected in NMR by
      nuclear Overhauser effect experiments. Strikingly, the amplitude of the observed
      ultrafast dynamics depends on the identity of the amino acid residues that are
      one helical turn away from Trp-18 in the peptides and is correlated with the
      level of biological function of their respective full-length proteins.

PMID- 12815094
TI  - Water at DNA surfaces: ultrafast dynamics in minor groove recognition.
AB  - Water molecules at the surface of DNA are critical to its equilibrium structure,
      DNA-protein function, and DNA-ligand recognition. Here we report direct probing
      of the dynamics of hydration, with femtosecond resolution, at the surface of a
      DNA dodecamer duplex whose native structure remains unperturbed on recognition in
      minor groove binding with the bisbenzimide drug (Hoechst 33258). By following the
      temporal evolution of fluorescence, we observed two well separated hydration
      times, 1.4 and 19 ps, whereas in bulk water the same drug is hydrated with time
      constants of 0.2 and 1.2 ps. For comparison, we also studied calf thymus DNA for
      which the hydration exhibits similar time scales to that of dodecamer DNA.
      However, the time-resolved polarization anisotropy is very different for the two
      types of DNA and clearly elucidates the rigidity in drug binding and difference
      in DNA rotational motions. These results demonstrate that hydration at the
      surface of the groove is a dynamical process with two general types of
      trajectories; the slowest of them (approximately 20 ps) are those describing
      dynamically ordered water. Because of their ultrafast time scale, the "ordered"
      water molecules are the most weakly bound and are accordingly involved in the
      entropic (hydration/dehydration) process of recognition.

PMID- 12815095
TI  - Neandertal faces were not long; modern human faces are short.
AB  - Neandertal faces have been described as being derived with respect to their
      overall length or degree of anterior projection. A comparison of cranial and
      mandibular indicators of lower facial projection across archaic and modern Homo
      indicates that Neandertal facial lengths on average are similar to those of
      preceding archaic Homo and principally contrast with those of recent humans.
      Neandertal facial length is not derived. The shortness of recent human facial
      skeletons is the evolutionarily derived condition.

PMID- 12815096
TI  - Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin
      exposure and ameliorates its fibrotic effects.
AB  - Previously we described a reliable method based on immunodepletion for isolating
      mesenchymal stem cells (MSCs) from murine bone marrow and showed that, after
      intracranial transplantation, the cells migrated throughout forebrain and
      cerebellum and adopted neural cell fates. Here we systemically administered MSCs
      purified by immunodepletion from male bleomycin (BLM)-resistant BALB/c mice into
      female BLM-sensitive C57BL/6 recipients and quantified engraftment levels in lung
      by real-time PCR. Male DNA accounted for 2.21 x 10(-5)% of the total lung DNA in
      control-treated mice but was increased 23-fold (P = 0.05) in animals exposed to
      BLM before MSC transplantation. Fluorescence in situ hybridization revealed that
      engrafted male cells were localized to areas of BLM-induced injury and exhibited
      an epithelium-like morphology. Moreover, purification of type II epithelial cells
      from the lungs of transplant recipients resulted in a 3-fold enrichment of male,
      donor-derived cells as compared with whole lung tissue. MSC administration
      immediately after exposure to BLM also significantly reduced the degree of BLM
      induced inflammation and collagen deposition within lung tissue. Collectively,
      these studies demonstrate that murine MSCs home to lung in response to injury,
      adopt an epithelium-like phenotype, and reduce inflammation and collagen
      deposition in lung tissue of mice challenged with BLM.

PMID- 12815097
TI  - Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of
      megalin and cubilin in kidney proximal tubules.
AB  - Loss of the renal endosome-associated chloride channel, ClC-5, in Dent's disease
      and knockout (KO) mice strongly inhibits endocytosis of filtered proteins by
      kidney proximal tubular cells (PTC). The underlying mechanism remains unknown. We
      therefore tested whether this endocytic failure could primarily reflect a loss of
      reabsorption by the multiligand receptors, megalin, and cubilin, caused by a
      trafficking defect. Impaired protein endocytosis in PTC of ClC-5 KO mice was
      demonstrated by (i) a major decreased uptake of injected 125I-beta 2
      microglobulin, but not of the fluid-phase tracer, FITC-dextran, (ii) reduced
      labeling of endosomes by injected peroxidase and for the endogenous
      megalin/cubilin ligands, vitamin D- and retinol-binding proteins, and (iii)
      urinary appearance of low-molecular-weight proteins and the selective cubilin
      ligand, transferrin. Contrasting with preserved mRNA levels, megalin and cubilin
      abundance was significantly decreased in kidney extracts of KO mice. Percoll
      gradients resolving early and late endosomes (Rab5a, Rab7), brush border (villin,
      aminopeptidase M), and a dense peak comprising lysosomes (acid hydrolases) showed
      a disappearance of the brush border component for megalin and cubilin in KO mice.
      Quantitative ultrastructural immunogold labeling confirmed the overall decrease
      of megalin and cubilin in PTC and their selective loss at the brush border. In
      contrast, total contents of the rate-limiting endocytic catalysts, Rab5a and
      Rab7, were unaffected. Thus, impaired protein endocytosis caused by invalidation
      of ClC-5 primarily reflects a trafficking defect of megalin and cubilin in PTC.

PMID- 12815098
TI  - A large pool of releasable vesicles in a cortical glutamatergic synapse.
AB  - To probe exocytosis at a cortical glutamatergic synapse, we made capacitance
      measurements in whole-cell recorded hippocampal mossy fiber terminals. Evaluation
      of different methods by using a morphology-based equivalent electrical model
      revealed that quantitative capacitance measurements are possible in this
      presynaptic structure. Voltage pulses leading to presynaptic Ca2+ inflow evoked
      large capacitance signals that showed saturation with increasing pulse duration.
      The mean peak capacitance increase was 100 fF, corresponding to a pool of
      approximately 1,400 releasable vesicles. Thus hippocampal mossy fiber synapses
      have a vesicular "maxipool." Large pool size and rapid vesicle recycling may
      underlie the uniquely large extent of activity-dependent plasticity in this
      synapse.

PMID- 12815099
TI  - R5 HIV productively infects Langerhans cells, and infection levels are regulated
      by compound CCR5 polymorphisms.
AB  - Langerhans cells (LCs) are suspected to be initial targets for HIV after sexual
      exposure (by becoming infected or by capturing virus). Here, productive R5 HIV
      infection of LC ex vivo and LC-mediated transmission of virus to CD4+ T cells
      were both found to depend on CCR5. By contrast, infection of monocyte-derived
      dendritic cells and transfer of infection from monocyte-derived dendritic cells
      to CD4+ T cells were mediated by CCR5-dependent as well as DC-specific ICAM-3
      grabbing nonintegrin-dependent pathways. Furthermore, in 62 healthy individuals,
      R5 HIV infection levels in LCs ex vivo were associated with CCR5 genotype.
      Specifically, genotyping for ORF Delta 32 revealed that LCs isolated from ORF
      Delta 32/wt individuals were significantly less susceptible to HIV when compared
      with LCs isolated from ORFwt/wt individuals (P = 0.016). Strikingly, further
      genetic analyses of the A-2459G CCR5 promoter polymorphism in ORF Delta 32/wt
      heterozygous individuals revealed that LCs isolated from -2459A/G + ORF Delta
      32/wt individuals were markedly less susceptible to HIV than were LCs from 
      2459A/A + ORF Delta 32/wt individuals (P = 0.012). Interestingly, these genetic
      susceptibility data in LCs parallel those of genetic susceptibility studies
      performed in cohorts of HIV-infected individuals. Thus, we suggest that CCR5
      mediated infection of LCs, and not capture of virus by LCs, provides a biologic
      basis for understanding certain aspects of host genetic susceptibility to initial
      HIV infection.

PMID- 12815100
TI  - A SNARE complex containing SGR3/AtVAM3 and ZIG/VTI11 in gravity-sensing cells is
      important for Arabidopsis shoot gravitropism.
AB  - Plants can sense the direction of gravity and change the growth orientation of
      their organs. The molecular mechanisms of gravity sensing and signal transduction
      during gravitropism are not well known. We have isolated several shoot
      gravitropism (sgr) mutants of Arabidopsis. The sgr3-1 mutant exhibits a reduced
      gravitropic response in the inflorescence stems. In the inflorescence stems of
      Arabidopsis, gravity is sensed in endodermal cells that contain sedimentable
      amyloplasts. In sgr3-1, some amyloplasts in the endodermis failed to sediment in
      the direction of gravity. SGR3 encodes a syntaxin, AtVAM3, which had previously
      been cloned as a homologue of yeast Vam3p. AtVAM3 is localized to the prevacuolar
      compartment and vacuole and is suggested to function in vesicle transport to the
      vacuole. We have also cloned another soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE), ZIG/AtVTI11, a mutation that causes abnormal
      gravitropism. This mutant displayed an abnormal distribution of amyloplasts in
      the endodermal cells similar to that in sgr3-1. Endodermis-specific expression of
      SGR3 and ZIG by using the SCR promoter could complement the abnormal shoot
      gravitropism of each mutant. Protein-protein interaction between AtVAM3 and
      AtVTI11 in the endodermal cells was detected immunologically. The sgr3-1 mutation
      appeared to reduce the affinity of AtVAM3 for AtVTI11 or SYP5. These results
      suggest that vesicle transport to the prevacuolar compartment/vacuole in the
      endodermal cells, mediated by a specific SNARE complex containing AtVAM3 and
      AtVTI11, plays an important role in shoot gravitropism.

PMID- 12815101
TI  - Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is
      preferentially selected for degradation.
AB  - The exocytic pathway provides a physical route through which newly synthesized
      secretory and membrane proteins are deployed to the eukaryote cell surface. For
      newly synthesized alpha1-antitrypsin (AAT), the modification of its asparagine
      linked oligosaccharides by a slow-acting mannosidase partitions the misfolded
      monomer into the proteasomal degradation pathway. Herein, we asked whether, and
      how, modification by endoplasmic reticulum mannosidase I (ERManI) contributes to
      the preferential selection of the misfolded AAT monomer for proteasomal
      degradation. Transiently expressed mutant and WT AAT variants underwent rapid
      destabilization in response to an artificially elevated ERManI concentration in
      the murine hepatoma cell line, Hepa1a. Based on the mannosidase- and lactacystin
      sensitive properties of intracellular turnover, a stochastic model is proposed in
      which the delayed onset of the glycan modification, relative to the duration of
      nonnative protein structure, coordinates the preferential degradation of the
      misfolded monomer and spares the native molecule from destruction. Newly
      synthesized endogenous transferrin underwent degradation in response to an
      elevated concentration of ERManI, whereas the nonglycosylated secretory
      glycoprotein albumin was not affected. Taken together, these findings indicate
      that efficient conformational maturation might function as the initial quality
      control standard for a broad population of glycoproteins.

PMID- 12815102
TI  - Glycation of the amyloid beta-protein by a nicotine metabolite: a fortuitous
      chemical dynamic between smoking and Alzheimer's disease.
AB  - The origin of Alzheimer's disease (AD) has been subjected to an intense amount of
      examination; however, a clear conclusion as to the nature of this crippling
      disease has yet to be identified. What is readily accepted is that a definitive
      marker of this disease is the aggregation of the amyloid beta-peptide (A beta)
      into neuritic plaques. The recent observation that nicotine exposure leads to
      delayed onset of AD has stimulated a flurry of research into the nature of this
      neuroprotective effect. This phenomenon has been debated, but no consensus has
      been reached, and although these studies have targeted nicotine, the primary
      alkaloid in tobacco, few studies have considered the physiological role of
      nicotine metabolites in disease states. Nornicotine is a major nicotine
      metabolite in the CNS and has been shown to participate in the aberrant glycation
      of proteins in vivo in a process termed nornicotine-based glycation. Herein is
      detailed a potentially fortuitous role of nornicotine-based glycation in relation
      to the pathology of AD. Specifically, nornicotine was found to covalently alter A
      beta, leading to reduced peptide aggregation. Potential consequences of this
      reaction cascade include reduced plaque formation and/or altered clearance of the
      peptide, as well as attenuated toxicity of soluble A beta aggregates. The
      findings described provide an alternative mechanism for nicotine neuroprotection
      in AD and a means for the alteration of amyloid folding based on a covalent
      chemical event.

PMID- 12815103
TI  - Reversal of age-related learning deficits and brain oxidative stress in mice with
      superoxide dismutase/catalase mimetics.
AB  - Oxidative stress has been implicated in cognitive impairment in both old
      experimental animals and aged humans. This implication has led to the notion that
      antioxidant defense mechanisms in the brain are not sufficient to prevent age
      related increase in oxidative damage and that dietary intake of a variety of
      antioxidants might be beneficial for preserving brain function. Here we report a
      dramatic loss of learning and memory function from 8 to 11 months of age in mice,
      associated with marked increases in several markers of brain oxidative stress.
      Chronic systemic administration of two synthetic catalytic scavengers of reactive
      oxygen species, Eukarion experimental compounds EUK-189 and EUK-207, from 8 to 11
      months almost completely reversed cognitive deficits and increase in oxidative
      stress taking place during this time period in brain. In particular, increase in
      protein oxidation was completely prevented, whereas increase in lipid
      peroxidation was decreased by approximately 50%. In addition, we observed a
      significant negative correlation between contextual fear learning and levels of
      protein oxidation in brain. These results further support the role of reactive
      oxygen species in age-related learning impairment and suggest potential clinical
      applications for synthetic catalytic scavengers of reactive oxygen species.

PMID- 12815104
TI  - Analysis of the distributed computing approach applied to the folding of a small
      beta peptide.
AB  - In the recently proposed distributed computing approach to protein folding a very
      large number of short independent simulations is performed. Using this method,
      folding events on a time scale orders of magnitude shorter than the experimental
      one have been reported. However, it has also been observed that the folding
      process is not an elementary kinetic step and that the presence of initial lag
      phases can bias short simulations toward atypical pathways. We study here a 20
      residue three-stranded antiparallel beta-sheet peptide whose equilibrium
      properties can be characterized by atomistic molecular dynamics simulations. We
      found that the folding rate of this peptide is estimated correctly by the
      distributed computing approach when trajectories > approximately 1/100 of the
      equilibrium folding time are considered. We also found that the fastest folding
      events occur through high-energy pathways, which are unlikely under equilibrium
      conditions. These very fast folding pathways do not relax within the equilibrium
      denatured state that is stabilized by the transient presence of both native and
      non-native interactions, and they are characterized by the nearly simultaneous
      formation of the two beta-hairpins and a very small number of non-native
      contacts.

PMID- 12815105
TI  - Genomic transcriptional profiling of the developmental cycle of Chlamydia
      trachomatis.
AB  - Chlamydia trachomatis is one of the most common bacterial pathogens and is the
      etiological agent of debilitating sexually transmitted and ocular diseases in
      humans. The organism is an obligate intracellular prokaryote characterized by a
      highly specialized biphasic developmental cycle. We have performed genomic
      transcriptional analysis of the chlamydial developmental cycle. This approach has
      led to the identification of a small subset of genes that control the primary
      (immediate-early genes) and secondary (late genes) differentiation stages of the
      cycle. Immediate-early gene products initiate bacterial metabolism and
      potentially modify the bacterial phagosome to escape fusion with lysosomes. One
      immediate early gene (CT147) is a homolog of the human early endosomal antigen-1
      that is localized to the chlamydial phagosome; suggesting a functional role for
      CT147 in establishing the parasitophorous vacuole in a nonfusogenic pathway. Late
      gene products terminate bacterial cell division and constitute structural
      components and remodeling activities involved in the formation of the highly
      disulfide cross-linked outer-membrane complex that functions in attachment and
      invasion of new host cells. Many of the genes expressed during the immediate
      early and late differentiation stages are Chlamydia-specific and have
      evolutionary origins in eukaryotic lineages.

PMID- 12815106
TI  - Illustrating the coupled human-environment system for vulnerability analysis:
      three case studies.
AB  - The vulnerability framework of the Research and Assessment Systems for
      Sustainability Program explicitly recognizes the coupled human-environment system
      and accounts for interactions in the coupling affecting the system's responses to
      hazards and its vulnerability. This paper illustrates the usefulness of the
      vulnerability framework through three case studies: the tropical southern
      Yucatan, the arid Yaqui Valley of northwest Mexico, and the pan-Arctic. Together,
      these examples illustrate the role of external forces in reshaping the systems in
      question and their vulnerability to environmental hazards, as well as the
      different capacities of stakeholders, based on their access to social and
      biophysical capital, to respond to the changes and hazards. The framework proves
      useful in directing attention to the interacting parts of the coupled system and
      helps identify gaps in information and understanding relevant to reducing
      vulnerability in the systems as a whole.

PMID- 12815107
TI  - Identification of the beta cell antigen targeted by a prevalent population of
      pathogenic CD8+ T cells in autoimmune diabetes.
AB  - Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and
      destroy the insulin-producing pancreatic beta cells. CD8+ T cells are essential
      for this beta cell destruction, yet their specific antigenic targets are largely
      unknown. Here, we reveal that the autoantigen targeted by a prevalent population
      of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6
      phosphatase catalytic subunit-related protein (IGRP). Through tetramer
      technology, IGRP-reactive T cells are readily detected in islets and peripheral
      blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility
      locus, suggesting that IGRP also may be an antigen for pathogenic T cells in
      human type 1 diabetes and, thus, a new, potential target for diagnostic and
      therapeutic approaches.

PMID- 12815108
TI  - Nur77 as a survival factor in tumor necrosis factor signaling.
AB  - The immediate-early gene Nur77, which encodes an orphan nuclear receptor, is
      rapidly induced by various stress stimuli, including tumor necrosis factor (TNF).
      Nur77 has been implicated in mediating apoptosis, particularly in T cells and
      tumor cells. We report here that Nur77 can play a role in antagonizing apoptosis
      in TNF signaling. Nur77 expression is strongly induced by TNF. Interestingly,
      unlike most antiapoptotic molecules, this induced expression of Nur77 is largely
      independent of NF-kappa B. Ectopic expression of Nur77 can protect wild-type,
      TRAF2-/-, and RelA-/- cells from apoptosis induced by TNF, whereas expression of
      a dominant-negative form of Nur77 (DN-Nur77) accelerates TNF-mediated cell death
      in the mutant cells. In mouse embryonic fibroblasts, Nur77 remains in the nucleus
      in response to TNF and is not translocated to the mitochondria, where it was
      reported to mediate apoptosis. Our results suggest that Nur77 is a survival
      effector protein in the context of TNF-mediated signaling.

PMID- 12815109
TI  - Conservation of genome content and virulence determinants among clinical and
      environmental isolates of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a ubiquitous environmental bacterium capable of causing
      a variety of life-threatening human infections. The genetic basis for
      preferential infection of certain immunocompromised patients or individuals with
      cystic fibrosis by P. aeruginosa is not understood. To establish whether
      variation in the genomic repertoire of P. aeruginosa strains can be associated
      with a particular type of infection, we used a whole-genome DNA microarray to
      determine the genome content of 18 strains isolated from the most common human
      infections and environmental sources. A remarkable conservation of genes
      including those encoding nearly all known virulence factors was observed.
      Phylogenetic analysis of strain-specific genes revealed no correlation between
      genome content and infection type. Clusters of strain-specific genes in the P.
      aeruginosa genome, termed variable segments, appear to be preferential sites for
      the integration of novel genetic material. A specialized cloning vector was
      developed for capture and analysis of these genomic segments. With this capture
      system a site associated with the strain-specific ExoU cytotoxin-encoding gene
      was interrogated and an 80-kb genomic island carrying exoU was identified. These
      studies demonstrate that P. aeruginosa strains possess a highly conserved genome
      that encodes genes important for survival in numerous environments and allows it
      to cause a variety of human infections. The acquisition of novel genetic
      material, such as the exoU genomic island, through horizontal gene transfer may
      enhance colonization and survival in different host environments.

PMID- 12815110
TI  - Effects of oxygen-induced lung damage on megakaryocytopoiesis and platelet
      homeostasis in a rat model.
AB  - The association between lung injury and thrombocytopenia was investigated by
      comparing the megakaryocyte and platelet counts, and platelet activation using P
      selectin as a marker, between the prepulmonary (right atrial) and postpulmonary
      (left atrial) blood in adult and neonatal (preterm and term) rats with and
      without hyperoxic lung injury. In the healthy controls, the postpulmonary blood
      had lower megakaryocyte count (prepulmonary versus postpulmonary: Preterm:
      8.7[0.6] versus 3.9[0.3] per ml, p < 0.001; Term: 8.7[1.1] versus 2.6[0.4] per
      ml, p < 0.001; Adult: median [interquartile ranges]: 2.5[1.0, 5.0] versus 1.0[0,
      3.0] per ml, p < 0.001), higher platelet count (prepulmonary versus
      postpulmonary: Preterm: 491.2[11.1] x 10(9)/L versus 595.1[10.2] x 10(9)/L, p <
      0.001; Term: 472.5[19.9] x 10(9)/L versus 579.3[26.2] x 10(9)/L, p < 0.001;
      Adult: 513.9[31.5] x 10(9)/L versus 664.7[28.8] x 10(9)/L, p < 0.001), but
      similar P-selectin expression. In contrast, the lung-damaged animals did not show
      any such differences in either megakaryocyte or platelet count, but P-selectin
      expression was greater in the postpulmonary blood (prepulmonary versus
      postpulmonary: Preterm: 38.7[3.9] versus 56.4[4.9]% platelets, p = 0.02; Term:
      40.9[2.0] versus 54.0[4.2]% platelets, p = 0.002; Adults: 30.0[3.6] versus
      49.1[4.7]% platelets, p = 0.003). Peripheral platelet and intra-pulmonary
      megakaryocyte counts in the lung-damaged rats were significantly lower than those
      in their respective controls. Intra-pulmonary thrombi or platelet aggregation
      were detected in the lung-damaged rats but not in the controls. These findings
      showed that hyperoxic lung damage reduced circulating platelets through (1)
      failure of the lungs to retain and fragment megakaryocytes to release platelets,
      and (2) platelet activation leading to platelet aggregation, thrombi formation
      and platelet consumption. The magnitude of platelet reduction was physiologically
      significant, as demonstrated by higher counts of megakaryocyte colony forming
      units in the bone marrow culture of the animals in the hyperoxia group when
      compared with the controls.

PMID- 12815111
TI  - The relationship of von Willebrand factor binding to activated platelets from
      healthy neonates and adults.
AB  - von Willebrand Factor (VWF) is important in platelet adhesion and shear-dependent
      platelet activation. We performed flow cytometric analyses of VWF binding to and
      activation of platelets from healthy neonates, children, and adults. Platelets
      from cord blood (n = 38; gestational age: 36-42 wk; birth weight: 2.4-5.1 kg),
      neonatal venous blood (n = 19; d 2-3 of life), children (n = 15; age: 1.5-16.3
      y), and adults (n = 22; age: 18-55 y) were studied. Binding of VWF was assessed
      using an antihuman VWF polyclonal antibody and a FITC-conjugated secondary
      antibody. Platelet activation was determined by the expression of CD62P, CD63,
      CD41, CD42b, activated GPIIb/IIIa (PAC-1), procoagulant surface (as reflected by
      annexin V binding), and microparticle formation. Although the mean percentage of
      VWF-positive platelets was not significantly higher in unstimulated platelets
      from 2- to 3-d-old neonates, their platelets were more activated than those from
      adults, and there was a positive correlation of VWF binding with platelet
      activation (CD62P: r = 0.74, p < 0.001; annexin V: r = 0.46, p < 0.05). In
      adults, after in vitro activation of platelets with thrombin and ADP, VWF binding
      to platelets increased and correlated significantly with CD62P expression (r =
      0.71, p < 0.001). VWF binding to unstimulated neonatal platelets was, however,
      higher than that to in vitro-stimulated platelets from adults at the same level
      of expression of platelet activation markers. Further studies are required to
      assess the mechanism and significance of VWF binding to activated platelets in
      the neonatal period.

PMID- 12815112
TI  - Effects of allopurinol and deferoxamine on reperfusion injury of the brain in
      newborn piglets after neonatal hypoxia-ischemia.
AB  - The hypothesis was tested that treatment with allopurinol, a xanthine oxidase
      inhibitor, or deferoxamine, a chelator of nonprotein-bound iron, preserved
      cerebral energy metabolism, attenuated development of edema, and improved
      histologic outcome in the newborn piglet at 24 h after hypoxia-ischemia. Thirty
      two newborn piglets were subjected to 1 h of hypoxia-ischemia by occluding both
      carotid arteries and reducing the fraction of inspired oxygen; five newborn
      piglets served as sham-operated controls. The depth of hypoxia-ischemia was
      controlled by phosphorous magnetic resonance spectroscopy. Upon reperfusion and
      reoxygenation, piglets received vehicle (n= 12), allopurinol (30 mg/kg/d, n =
      10), or deferoxamine (12.5 mg/kg/d, n = 10). The cerebral energy status was
      determined with phosphorous magnetic resonance spectroscopy. The presence of
      vasogenic edema was assessed by T2-weighted magnetic resonance imaging. Brain
      cell injury was assessed with caspase-3 activity, histology, and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end (TUNEL)
      labeling. At 24 h after hypoxia-ischemia, the phosphocreatine/inorganic phosphate
      ratios were significantly decreased in vehicle-treated, but not in allopurinol-
      or deferoxamine-treated piglets. Water T2 values were significantly increased at
      24 h after hypoxia-ischemia in cerebral cortex, thalamus, and striatum of vehicle
      treated piglets, but not in allopurinol- and deferoxamine-treated piglets. No
      differences in caspase-3 activity, histologic outcome, or TUNEL-labeling were
      demonstrated between the three treatment groups. We suggest that allopurinol and
      deferoxamine may have an additional value in the treatment of perinatal hypoxia
      ischemia with other neuroprotective agents or in combination with hypothermia.

PMID- 12815113
TI  - The role of parenteral lipids in supporting gluconeogenesis in very premature
      infants.
AB  - We have previously demonstrated that very premature infants receiving glucose at
      17 micromol/kg min plus appropriate supply of parenteral lipids (Intralipid) and
      amino acids (TrophAmine) maintained normoglycemia by glucose produced primarily
      via gluconeogenesis. The present study addressed the individual roles of
      parenteral lipids and amino acids in supporting gluconeogenesis. Fourteen
      premature infants (993 +/- 36 g 27 +/- 1 wk) (mean +/- SE) were studied for 8 h
      on d 5 +/- 1 of life. All infants were receiving standard TPN prior to the study.
      At start of study, the glucose infusion rate was decreased to approximately 17
      micromol/kg min and either Intralipid (g + AA; n = 8) or TrophAmine (g + IL; n =
      6) was discontinued. Data from 14 previously studied infants receiving glucose
      (approximately 17 micromol/kg min) + TrophAmine + Intralipid (g + AA + IL) are
      included for comparison. Gluconeogenesis was measured by [U-13 C]glucose, (g +
      AA) and (8 infants of the g + AA + IL group) or [2-13C]glycerol, (g + IL) and (6
      infants of the g + AA + IL group). Infants studied by the same method were
      compared. Withdrawal of Intralipid resulted in decreased gluconeogenesis, 6.3 +/-
      0.9 (g +AA) vs. 8.4 +/- 0.7 micromol/kg min (g + AA + IL) (p = 0.03). Withdrawal
      of TrophAmine affected neither total gluconeogenesis, 7.5 +/- 0.8 vs. 7.9 +/- 0.9
      micromol/kg min nor gluconeogenesis from glycerol, 4.4 +/- 0.6 vs. 4.9 +/- 0.7
      micromol/kg min (g+ IL and g + AA + IL groups, respectively). In conclusion, in
      parenterally fed very premature infants, lipids play a primary role in supporting
      gluconeogenesis.

PMID- 12815114
TI  - Diaphragmatic function in infants with surgically corrected anomalies.
AB  - Infants with surgically correctable anomalies, abdominal wall defects (AWD) or
      congenital diaphragmatic hernia (CDH) may have poor postnatal diaphragmatic
      function, because the low intra-abdominal pressure experienced by such patients
      in utero could result in impaired diaphragmatic development. Our objective was to
      compare postoperative diaphragmatic function of infants with CDH or AWD to that
      of gestational age-matched controls. Diaphragmatic function was assessed by
      measurement of the transdiaphragmatic pressure and maximum inspiratory pressure
      at the mouth generated during crying against an occlusion. In addition, the
      transdiaphragmatic pressure produced by unilateral and/or bilateral magnetic
      stimulation of the phrenic nerves (TwPdi) was examined. Lung volume was assessed
      by measurement of functional residual capacity (FRC) using a helium gas dilution
      technique. Ten infants with CDH, 26 with AWD infants (19 gastroschisis, seven
      exomphalos), and 36 gestational age-matched controls were studied. Compared with
      their matched controls, the eight CDH infants with left-sided defects had
      significantly lower left (p < 0.01) and right (p < 0.05) TwPdi and FRC (p <
      0.01), and the gastroschisis infants, but not those with exomphalos, had
      significantly lower left and right TwPdi (p < 0.05). There were no significant
      differences in transdiaphragmatic pressure and maximum inspiratory pressure at
      the mouth between the CDH or AWD infants and the controls. Diaphragmatic function
      postoperatively is impaired in infants with CDH or gastroschisis.

PMID- 12815115
TI  - Safety and efficacy of intratracheal recombinant human Clara cell protein in a
      newborn piglet model of acute lung injury.
AB  - Despite the widespread use of exogenous surfactant, acute and chronic lung injury
      continues to be a major cause of morbidity in preterm infants. CC10 is a protein
      produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory
      and antifibrotic properties. We studied whether intratracheal (IT) recombinant
      human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn
      piglet model of acute lung injury. Twenty-nine newborn piglets were given
      Survanta and then ventilated for 48 h receiving the following: room air (group
      1); 100% O2 (group 2); or 100% O2 and 25, 5, or 1 mg/kg (groups 3, 4, and 5,
      respectively) of IT rhCC10 (diluted to 2 mL/kg with saline) at time 0. Laboratory
      studies, oxygen ratios, static pressure-volume curves, bronchoalveolar lavage
      (for inflammatory markers), and histologic analyses were performed over the 48-h
      study period. Pulmonary compliance and oxygenation were significantly improved in
      animals receiving 5 mg/kg IT rhCC10 compared with room air and 100% O2 controls
      (p < 0.004 and p < 0.05, respectively, ANOVA). Reductions in inflammatory markers
      were seen in animals receiving rhCC10, although changes did not reach statistical
      significance. No significant toxicity was noted. rhCC10 appeared safe and
      improved pulmonary function in this newborn piglet model of hyperoxic lung
      injury. We speculate that rhCC10 may represent a promising therapy for the
      prevention of lung injury in preterm infants.

PMID- 12815116
TI  - No association between preeclampsia or cesarean section and incidence of type 1
      diabetes among children: a large, population-based cohort study.
AB  - The objective was to investigate whether selected perinatal factors, as
      indicators of perinatal exposures, are associated with the risk of type 1
      diabetes in children. Specifically, we tested whether maternal preeclampsia,
      Rhesus-immunization, induced labor, cesarean section, and multiple birth were
      associated with incidence of type 1 diabetes. A cohort study was designed by
      linking records of the Medical Birth Registry and the National Childhood Diabetes
      Registry of Norway. Live births in the study period were followed for a maximum
      of 15 y and contributed 8,166,731 person-years between 1989 and 1998. Altogether,
      1824 cases of type 1 diabetes diagnosed between 1989 and 1998 were identified
      within the cohort. There was a suggestive, but nonsignificant, increase in risk
      of type 1 diabetes associated with Rhesus-immunization. Maternal preeclampsia,
      cesarean section, and the other perinatal factors investigated in this study were
      not significantly associated with incidence of type 1 diabetes in the children.
      Previous indications that cesarean section and preeclampsia are associated with
      type 1 diabetes were not supported by this large study. The majority of routinely
      recorded perinatal factors are only weakly associated with type 1 diabetes, or
      not at all.

PMID- 12815117
TI  - Pregnancy in mice lacking the vitamin D receptor: normal maternal skeletal
      response, but fetal hypomineralization rescued by maternal calcium
      supplementation.
AB  - Fetal mineralization appears to be driven by the pregnancy-induced stimulation of
      intestinal Ca absorption. We thus hypothesized that mineralization would be
      impaired in fetuses of mice that lack the vitamin D receptor (VDR). Here we
      report on the maternal response to pregnancy, and the fetal mineralization, in
      mice with a homozygous disruption of the VDR gene (VDR-/-) mated with wild-type
      (wt) males. We found that VDR-/- mice show mild hypocalcemia, clear rickets and
      osteomalacia on bone histomorphometry, lower cortical bone density on
      quantitative tomography, and reduced concentrations of calbindin-D9k (CaBP-D9k)
      in duodenal mucosa and kidney. The skeletal response to pregnancy was comparable
      in wt and VDR-/- mice; duodenal CaBP-D9k concentrations increased during
      pregnancy in VDR-/- as in wt mice, but remained 40% lower than in wt mice. We
      confirmed our hypothesis that mineralization is defective in d18.5 VDR+/- fetuses
      of VDR-/- mice, both by whole-body Ca determination and histomorphometric
      evaluation; the number of osteoclastic cells in bone was increased. The fetuses
      were hypercalcemic and had a 5-fold increase in circulating 1,25(OH)2D3. We then
      studied pregnancies in VDR-/- females, mated with wt males, fed a high
      Ca/P/lactose rescue diet during pregnancy. The rescue diet normalized the
      mineralization, the number of osteoclastic cells, and plasma Ca and 1,25(OH)2D3
      concentrations in the fetuses. We interpret the data as evidence that, to ensure
      normal fetal mineralization, the maternal VDR-dependent intestinal Ca absorption
      can be substituted by passive Ca absorption entrained by a higher Ca intake.
      Alternatively or additionally, elevated 1,25(OH)2D3 in utero may disturb bone
      development.

PMID- 12815118
TI  - SARS: health care work can be hazardous to health.

PMID- 12815119
TI  - Stress prevention in the police.

PMID- 12815120
TI  - Poor communication between health professionals is a barrier to rehabilitation.

PMID- 12815121
TI  - The interaction between general practitioners and occupational health
      professionals in relation to rehabilitation for work: a Delphi study.
AB  - BACKGROUND: Anecdotally, communication between general practitioners (GPs) and
      occupational health professionals is poor and acts as a barrier to successful
      rehabilitation for work. It is not known how widely this view is held by the many
      stakeholders in rehabilitation for work, or how important the observation is in
      its effect. METHODS: A Delphi study was conducted by initial semi-structured
      telephone interview, followed by a three-round collation and feedback of opinion
      by e-mail. The 25 participants were identified by suggestion within the study
      process for their position as key informants within a wide range of stakeholders.
      RESULTS: The process generated a consensus statement which identifies the
      extremely important nature of rehabilitation for work, the crucial role by GPs,
      the central role of occupational health professionals in case management and the
      barrier represented by the often very poor communication between them.
      CONCLUSION: The way forward is to improve communication by mutual education and
      understanding and a team approach to rehabilitation strategy. This may be
      facilitated by the GPs who work in occupational health and disability assessment
      and the involvement of other health professionals to great benefit for all
      stakeholders.

PMID- 12815122
TI  - Rehabilitation and retention in the workplace--the interaction between general
      practitioners and occupational health professionals: a consensus statement.

PMID- 12815123
TI  - Stress in police officers: a study of the origins, prevalence and severity of
      stress-related symptoms within a county police force.
AB  - BACKGROUND: High levels of stress-related illness are causing concern across
      industry. Against a background of impending legislative moves to try to improve
      this situation, there is a need to identify key work-related stressors. Police
      work tends to be regarded as inherently stressful because of the personal risk of
      exposure to confrontation and violence and the day-to-day involvement in a
      variety of traumatic incidents. As a result, high levels of stress-related
      symptoms might be expected in this population. OBJECTIVE: To examine the sources
      of stress-related symptoms within police officers and measure the prevalence of
      significant associated mental ill-health. METHOD: A cross-sectional questionnaire
      survey of a population of 1206 police officers was performed to assess levels of
      strain associated with a series of potential home and work related stressors.
      Participants were then split into low and high scoring groups on the basis of a
      General Health Questionnaire (GHQ) threshold score in order to identify those
      stressors most associated with mental ill-health effects. RESULTS: Occupational
      stressors ranking most highly within the population were not specific to
      policing, but to organizational issues such as the demands of work impinging upon
      home life, lack of consultation and communication, lack of control over workload,
      inadequate support and excess workload in general. The high scoring group
      constituted 41% of the population and differed significantly from those with low
      scores in perception of all stressors, ranking both personal and occupational
      stressors more highly, and from personality constraints appeared significantly
      more 'stress-prone'. A significant association between gender and mental ill
      health was found, with females more likely to score more highly on the GHQ than
      males. CONCLUSION: This study confirms previous findings of organizational
      culture and workload as the key issues in officer stress. Given that the degree
      of symptomatology appears to be worsening, management action is required. Further
      research is indicated within the police population into a possible increased
      susceptibility in female officers.

PMID- 12815124
TI  - The relationship between occupational psychological stress and female fertility.
AB  - OBJECTIVE: To investigate the association between occupational psychological
      stress and female fertility. METHODS: This was a case-control study including
      consecutive working female patients attending fertility and in vitro
      fertilization clinics in the Soroka University Medical Center. We compared
      occupational stress between 64 working patients who had attended the clinics due
      to female infertility (case group) and 106 working patients who had attended the
      clinics due to their partner's reproductive impairment (control group). RESULTS:
      Patients from the female infertility group were older (31.9 +/- 6.2 versus 30.2
      +/- 4.6, P = 0.047) and tended to participate more in sporting activity [23.4
      versus 10.4%, odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.05-6.73, P
      = 0.022] as compared with patients from the male infertility group. Patients from
      the case group tended to work more weekly hours as compared with the controls
      (33.6 +/- 16.8 versus 26.9 +/- 17.4, P = 0.028). High reliability was found, as
      demonstrated by Cronbach's alpha of 0.81-0.90 for the four burnout parameters.
      Patients from the female infertility group had significantly lower listlessness
      scores as compared with the control group, using the Mann-Whitney test (2.6 +/-
      1.1 versus 3.1 +/- 1.2, P = 0.013). CONCLUSIONS: Patients admitted due to female
      infertility tended to have lower listlessness scores as compared with patients
      admitted due to their partner's infertility problem. No significant association
      was found between other burnout, job strain and job satisfaction scores and
      women's fertility status.

PMID- 12815125
TI  - Occupational and social variation in subjective health complaints.
AB  - OBJECTIVES: Occupational and social factors are thought to be important
      determinants of health inequality. The aim of this study was to examine the
      relationships between occupation, lifestyle and subjective health complaints
      (SHC). METHODS: SHC and self-reported sickness absence were recorded in a cross
      sectional study of 662 individuals aged between 16 and 67 from five occupational
      groups: blue-collar, school/education, health service, white-collar and service.
      Differences in SHC and sickness absence were investigated. A model of
      sociodemographic, lifestyle and work-related factors was tested to examine
      associations with SHC. RESULTS: Few differences in SHC and sickness absence were
      found when educational level, age and gender were controlled for. Female health
      service workers did, however, show significantly higher prevalence of
      pseudoneurological complaints compared with white-collar workers. Male blue
      collar workers had significantly higher frequency of sickness absence than white
      collar workers; otherwise, there were no significant differences in frequency and
      duration of sickness absence. The model explained very little of the variance of
      SHC (R(2)(adj) = 0.15) and occupational group was not significantly associated
      with health. Physical workload and sleep quality showed significant relationships
      with SHC for both genders. Education, however, was a significant factor for women
      only. CONCLUSIONS: The differences in health found between major occupational
      groups in this sample were mainly explained by gender differences.
      Sociodemographic, lifestyle and work-related factors explained little of the
      variance in SHC, suggesting that factors such as psychological demands, perceived
      job stress, coping and other psychological factors might be of stronger
      importance for SHC.

PMID- 12815126
TI  - Performance and evaluation of small construction safety training simulations.
AB  - BACKGROUND: Back- and fall-related injuries occur frequently in construction and
      are costly in terms of workers' compensation claims and lost productivity.
      Interventions are needed that address the susceptibility to these injuries. AIMS:
      The purpose of this study was to develop and test a safety training intervention
      for small construction companies (</=10 employees) in Kentucky, USA. This paper
      will focus on the performance and evaluation of these simulation exercises, not
      their effectiveness in preventing injuries. METHODS: The intervention consisted
      of six latent-image narrative simulation exercises targeted at prevention of back
      or fall-related injuries, which emphasized both the economic impact of injuries
      and the benefits of individual and organizational prevention strategies.
      Participants included owner-operators, supervisors and employees. Analyses were
      completed to determine participant scores on the intervention along with their
      perceptions of the quality, realism and applicability of the training. RESULTS:
      Mean pooled performance scores (percentage correct) were 83.3% [standard
      deviation (SD) = 8.9, n = 143] for three back simulations and 85.2% (SD = 8.9, n
      = 159) for three fall-related simulations. Mean total evaluation scores
      (percentage of maximum) were 83.1% (SD = 11.6) and 85.5% (SD = 11.7) for the back
      and fall simulations, respectively. Quality and realism evaluation scores were
      significantly higher than scores for applicability to work. CONCLUSION:
      Simulations were well received as safety training exercises. Given the
      heterogeneous work classifications found in small construction companies, it may
      be preferable to target safety intervention content to specific trades rather
      than aim for generality across trades.

PMID- 12815127
TI  - Risk factors for low back pain among office workers in Ibadan, Southwest Nigeria.
AB  - BACKGROUND: Low back pain is the most common musculo-skeletal problem in the
      workplace. Data from low-income countries are scant. OBJECTIVES: To determine the
      prevalence and risk factors for low back pain among office workers in Ibadan,
      Nigeria. METHODS: A cross-sectional study design was utilized. Questionnaires
      were distributed among office workers in the civil service in Ibadan, Nigeria.
      RESULTS: Eight hundred and forty questionnaires were analysed, with a response
      rate of 66%. The 12 month prevalence of low back pain was 38% and the point
      prevalence was 20%. Low back pain was significantly associated with senior staff
      grade and smoking. Severity of low back pain was associated with sitting for >3
      h. Only 16 respondents (5%) reported sickness absence due to back pain in the
      previous year. A total of 75 days were lost, a mean of 4.7 days per year.
      CONCLUSIONS: The occurrence of low back pain in this study is comparable with
      that reported in studies from more industrialized countries, but does not
      constitute a major cause of sickness absence in this group of workers.

PMID- 12815128
TI  - What has psychiatry to contribute to industry? 1953.

PMID- 12815129
TI  - A vital issue in clinical aviation medicine.

PMID- 12815130
TI  - Monitor.

PMID- 12815131
TI  - Tales of Kieran: the occupational physician's odyssey.

PMID- 12815132
TI  - New horizons in oncologic imaging.

PMID- 12815133
TI  - Use it or lose it--do effortful mental activities protect against dementia?

PMID- 12815134
TI  - Noninvasive detection of clinically occult lymph-node metastases in prostate
      cancer.
AB  - BACKGROUND: Accurate detection of lymph-node metastases in prostate cancer is an
      essential component of the approach to treatment. We investigated whether highly
      lymphotropic superparamagnetic nanoparticles, which gain access to lymph nodes by
      means of interstitial-lymphatic fluid transport, could be used in conjunction
      with high-resolution magnetic resonance imaging (MRI) to reveal small nodal
      metastases. METHODS: Eighty patients with presurgical clinical stage T1, T2, or
      T3 prostate cancer who underwent surgical lymph-node resection or biopsy were
      enrolled. All patients were examined by MRI before and 24 hours after the
      intravenous administration of lymphotropic superparamagnetic nanoparticles (2.6
      mg of iron per kilogram of body weight). The imaging results were correlated with
      histopathological findings. RESULTS: Of the 334 lymph nodes that underwent
      resection or biopsy, 63 (18.9 percent) from 33 patients (41 percent) had
      histopathologically detected metastases. Of these 63 nodes, 45 (71.4 percent) did
      not fulfill the usual imaging criteria for malignancy. MRI with lymphotropic
      superparamagnetic nanoparticles correctly identified all patients with nodal
      metastases, and a node-by-node analysis had a significantly higher sensitivity
      than conventional MRI (90.5 percent vs. 35.4 percent, P<0.001) or nomograms.
      CONCLUSIONS: High-resolution MRI with magnetic nanoparticles allows the detection
      of small and otherwise undetectable lymph-node metastases in patients with
      prostate cancer.

PMID- 12815135
TI  - Staging of non-small-cell lung cancer with integrated positron-emission
      tomography and computed tomography.
AB  - BACKGROUND: We compared the diagnostic accuracy of integrated positron-emission
      tomography (PET) and computed tomography (CT) with that of CT alone, that of PET
      alone, and that of conventional visual correlation of PET and CT in determining
      the stage of disease in non-small-cell lung cancer. METHODS: In a prospective
      study, integrated PET-CT was performed in 50 patients with proven or suspected
      non-small-cell lung cancer. CT and PET alone, visually correlated PET and CT, and
      integrated PET-CT were evaluated separately, and a tumor-node-metastasis (TNM)
      stage was assigned on the basis of image analysis. Nodal stations were identified
      according to the mapping system of the American Thoracic Society. The standard of
      reference was histopathological assessment of tumor stage and node stage.
      Extrathoracic metastases were confirmed histopathologically or by at least one
      other imaging method. A paired sign test was used to compare integrated PET-CT
      with the other imaging methods. RESULTS: Integrated PET-CT provided additional
      information in 20 of 49 patients (41 percent), beyond that provided by
      conventional visual correlation of PET and CT. Integrated PET-CT had better
      diagnostic accuracy than the other imaging methods. Tumor staging was
      significantly more accurate with integrated PET-CT than with CT alone (P=0.001),
      PET alone (P<0.001), or visual correlation of PET and CT (P=0.013); node staging
      was also significantly more accurate with integrated PET-CT than with PET alone
      (P=0.013). In metastasis staging, integrated PET-CT increased the diagnostic
      certainty in two of eight patients. CONCLUSIONS: Integrated PET-CT improves the
      diagnostic accuracy of the staging of non-small-cell lung cancer.

PMID- 12815136
TI  - Leisure activities and the risk of dementia in the elderly.
AB  - BACKGROUND: Participation in leisure activities has been associated with a lower
      risk of dementia. It is unclear whether increased participation in leisure
      activities lowers the risk of dementia or participation in leisure activities
      declines during the preclinical phase of dementia. METHODS: We examined the
      relation between leisure activities and the risk of dementia in a prospective
      cohort of 469 subjects older than 75 years of age who resided in the community
      and did not have dementia at base line. We examined the frequency of
      participation in leisure activities at enrollment and derived cognitive-activity
      and physical-activity scales in which the units of measure were activity-days per
      week. Cox proportional-hazards analysis was used to evaluate the risk of dementia
      according to the base-line level of participation in leisure activities, with
      adjustment for age, sex, educational level, presence or absence of chronic
      medical illnesses, and base-line cognitive status. RESULTS: Over a median follow
      up period of 5.1 years, dementia developed in 124 subjects (Alzheimer's disease
      in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of
      dementia in 8). Among leisure activities, reading, playing board games, playing
      musical instruments, and dancing were associated with a reduced risk of dementia.
      A one-point increment in the cognitive-activity score was significantly
      associated with a reduced risk of dementia (hazard ratio, 0.93 [95 percent
      confidence interval, 0.90 to 0.97]), but a one-point increment in the physical
      activity score was not (hazard ratio, 1.00). The association with the cognitive
      activity score persisted after the exclusion of the subjects with possible
      preclinical dementia at base line. Results were similar for Alzheimer's disease
      and vascular dementia. In linear mixed models, increased participation in
      cognitive activities at base line was associated with reduced rates of decline in
      memory. CONCLUSIONS: Participation in leisure activities is associated with a
      reduced risk of dementia, even after adjustment for base-line cognitive status
      and after the exclusion of subjects with possible preclinical dementia.
      Controlled trials are needed to assess the protective effect of cognitive leisure
      activities on the risk of dementia.

PMID- 12815137
TI  - Prevalence of Celiac disease among children in Finland.
AB  - BACKGROUND: Wheat, rye, and barley proteins induce celiac disease, an autoimmune
      type of gastrointestinal disorder, in genetically susceptible persons. Because
      the disease may be underdiagnosed, we estimated the prevalence of the disease and
      tested the hypothesis that assays for serum autoantibodies can be used to detect
      untreated celiac disease and that positive findings correlate with specific HLA
      haplotypes. METHODS: Serum samples were collected from 3654 students (age range,
      7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue
      transglutaminase antibodies. HLA typing was also performed on stored blood
      samples. All antibody-positive subjects were asked to undergo small-bowel biopsy
      in 2001. RESULTS: Of the 3654 subjects, 56 (1.5 percent) had positive antibody
      tests, as determined in 2001. Results of the two antibody tests were highly
      concordant. As of 1994, none of the subjects had received a clinical diagnosis of
      celiac disease, but 10 who had positive tests for both antibodies in serum
      obtained in 1994 received the diagnosis between 1994 and 2001. Of the 36 other
      subjects with positive antibody assays who agreed to undergo biopsy in 2001, 27
      had evidence of celiac disease on biopsy. Thus, the estimated biopsy-proved
      prevalence was 1 case in 99 children. All but two of the antibody-positive
      subjects had either the HLA-DQ2 or the HLA-DQ8 haplotype. The prevalence of the
      combination of antibody positivity and an HLA haplotype associated with celiac
      disease was 1 in 67. CONCLUSIONS: The presence of serum tissue transglutaminase
      and endomysial autoantibodies is predictive of small-bowel abnormalities
      indicative of celiac disease. There is a good correlation between autoantibody
      positivity and specific HLA haplotypes. We estimate that the prevalence of celiac
      disease among Finnish schoolchildren is at least 1 case in 99 children.

PMID- 12815138
TI  - Images in clinical medicine. Acute vertebral osteomyelitis.

PMID- 12815139
TI  - Improving safety with information technology.

PMID- 12815140
TI  - Clinical practice. The solitary pulmonary nodule.

PMID- 12815141
TI  - Alport's syndrome, Goodpasture's syndrome, and type IV collagen.

PMID- 12815142
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 19-2003. A five-day-old girl with leukocytosis and a worsening
      rash from birth.

PMID- 12815143
TI  - Celiac disease--how to handle a clinical chameleon.

PMID- 12815144
TI  - Errors today and errors tomorrow.

PMID- 12815145
TI  - Celiac disease--the villain unmasked?

PMID- 12815146
TI  - Soluble CD40 ligand in acute coronary syndromes.

PMID- 12815147
TI  - The outbreak of conjunctivitis at Dartmouth.

PMID- 12815148
TI  - The death at Duke.

PMID- 12815149
TI  - The chromogranin-secretogranin family.

PMID- 12815150
TI  - Understanding and responding to adverse events.

PMID- 12815151
TI  - Race and genomics.

PMID- 12815152
TI  - Aspiration of barium.

PMID- 12815153
TI  - Interleukin-1-receptor antagonist in the Muckle-Wells syndrome.

PMID- 12815154
TI  - New insights into G-protein-coupled receptor signaling from the melanocortin
      receptor system.

PMID- 12815155
TI  - Identification of a site in GluR1 and GluR2 that is important for modulation of
      deactivation and desensitization.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of
      ionotropic glutamate receptors consists of rapidly gating ion channels. Positive
      modulation of channel gating may slow gating kinetics through at least two
      distinct mechanisms, evidenced by the predominant slowing of either the rate of
      receptor desensitization or the rate of offset after agonist withdrawal
      (deactivation). This study compares the actions of two positive allosteric
      modulators [cyclothiazide, which modulates desensitization, and 1-(1,4
      benzodioxan-6-ylcarbonyl)piperidine (CX546), which modulates deactivation] in a
      mutant shown previously to impede modulation by cyclothiazide. These experiments
      test the hypothesis that the point mutation, GluR1(S493T), would also cause a
      loss of modulation by CX546. Wild-type GluR1 through -4 receptors were modulated
      by CX546, as assayed by the potentiation of steady-state currents in the Xenopus
      laevis oocyte expression system. CX546 potentiated steady-state currents of both
      splice isoforms of GluR1. Modulation by CX546 was completely abolished in
      GluR1(S493T) and its homolog, GluR2(S497T), although this mutation did not affect
      apparent agonist affinity in the absence of CX546. Thus, the GluR1(S493T)
      mutation has a similar impairment of modulation by either cyclothiazide or CX546,
      indicating that some residues at the subunit interface of glutamate receptors
      play an important role in channel deactivation and desensitization.

PMID- 12815157
TI  - Allosteric site on muscarinic acetylcholine receptors: identification of two
      amino acids in the muscarinic M2 receptor that account entirely for the M2/M5
      subtype selectivities of some structurally diverse allosteric ligands in N
      methylscopolamine-occupied receptors.
AB  - Two epitopes have been identified recently to be responsible for the high
      affinity binding of alkane-bisammonium and caracurine V type allosteric ligands
      to N-methylscopolamine (NMS)-occupied M2 muscarinic acetylcholine receptors,
      relative to M5 receptors: the amino acid M2-Thr423 at the top of transmembrane
      region (TM) 7 and an epitope comprising the second extracellular loop (o2) of the
      M2 receptor including the flanking regions of TM4 and TM5. We aimed to find out
      whether a single amino acid could account for the contribution of this epitope to
      binding affinity. Allosteric interactions were investigated in wild-type and
      mutant receptors in which the orthosteric binding site was occupied by [3H]NMS (5
      mM Na,K,Pi buffer, pH 7.4, 23 degrees C). Using M2/M5 chimeric and point-mutated
      receptors, the relevant epitope was narrowed down to M2-Tyr177. A double point
      mutated M2 receptor in which both M2-Tyr177 and M2-Thr423 were replaced by the
      corresponding amino acids of M5 revealed that these two amino acids account
      entirely for the (approximately 100-fold) M2/M5 selectivity of the alkane
      bisammonium and the caracurine V type allosteric ligands. At NMS-free M2
      receptors, the caracurine V derivative also displayed approximately 100-fold
      M2/M5 selectivity, but the double point mutation reduced the M2 affinity by only
      approximately 10-fold; thus, additional epitopes may influence selectivity for
      the free receptors. A three-dimensional model of the M2 receptor was used to
      simulate allosteric agent docking to NMS-occupied receptors. M2-Tyr177 and M2
      Thr423 seem to be located near the junction of the allosteric and the orthosteric
      areas of the M2 receptor ligand binding cavity.

PMID- 12815156
TI  - Spatial regulation of Galphai protein signaling in clathrin-coated membrane
      microdomains containing GAIP.
AB  - Regulators of G-protein signaling (RGS) proteins are GTPase-activating proteins
      (GAPs) that bind to Galpha subunits and attenuate G protein signaling, but where
      these events occur in the cell is not yet established. Here we investigated, by
      immunofluorescence labeling and deconvolution analysis, the site at which
      endogenous Galpha-interacting protein (GAIP) (RGS19) binds to Galphai3-YFP and
      its fate after activation of delta-opioid receptor (DOR). In the absence of
      agonist, GAIP is spatially segregated from Galphai3 and DOR in clathrin-coated
      domains (CCPs) of the cell membrane (PM), whereas Galphai3-YPF and DOR are
      located in non-clathrin-coated microdomains of the PM. Upon addition of agonist,
      Galphai3 partially colocalizes with GAIP in CCPs at the PM. When endocytosis is
      blocked by expression of a dynamin mutant [dyn(K44A)], there is a striking
      overlap in the distribution of DOR and Galphai3-YFP with GAIP in CCPs. Moreover,
      Galphai3-YFP and GAIP form a coprecipitable complex. Our results support a model
      whereby, after agonist addition, DOR and Galphai3 move together into CCPs where
      Galphai3 and GAIP meet and turn off G protein signaling. Subsequently, Galphai3
      returns to non-clathrin-coated microdomains of the PM, GAIP remains stably
      associated with CCPs, and DOR is internalized via clathrin-coated vesicles. This
      constitutes a novel mechanism for regulation of Galpha signaling through spatial
      segregation of a GAP in clathrin-coated pits.

PMID- 12815158
TI  - Rescuing the traffic-deficient mutants of rat mu-opioid receptors with
      hydrophobic ligands.
AB  - Deletion of a sequence near the fifth transmembrane domain (258RLSKV262, i3-1
      mutant) and a motif residing at the proximal carboxyl tail (344KFCTR348, C-2
      mutant) resulted in mu-opioid receptor mutants that were poorly expressed on the
      surface of transfected human embryonic kidney 293 cells. Treatment with the
      opioid antagonist naloxone, the agonist etorphine, and other hydrophobic ligands
      enhanced cell surface expression of i3-1 and C-2 mutants. The observed
      enhancement was time- and concentration-dependent, required the ligands to be
      membrane permeable, and was not the result of the reversal of the constitutive
      activities of the mutant receptors. The binding of the ligands resulted in the
      trafficking of the mutant receptors retained in the endoplasmic reticulum to the
      cell surface. The cell surface-expressed mutant C-2, but not i3-1, fully retained
      ability to mediate inhibition of adenylyl cyclase activity. Furthermore, the
      Golgi-disturbing agents brefeldin A and monensin completely blocked naloxone
      enhanced expression of i3-1 and C-2 mutants. Results of these studies suggest
      that intracellular interactions of agonist and antagonist with mutant receptors
      can serve as chaperones in the trafficking of the mutants to the cell surface.

PMID- 12815159
TI  - Transgenic mouse models of human CYP3A4 gene regulation.
AB  - CYP3A4, the predominant but variably expressed cytochrome P450 of adult human
      liver, is subject to multifaceted constitutive regulation as well as
      transcriptional induction by a variety of structurally unrelated xenobiotics.
      Using transient transfections in HepG2 cells, we previously demonstrated the
      existence of a potent xenobiotic-responsive enhancer module located between - 7.2
      and - 7.8 kilobases upstream of the CYP3A4 transcription start site. Induction is
      mediated by interaction of transcription factor binding sites in the XREM with
      the nuclear receptors pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR). To determine the in vivo relevance of these findings and to
      establish a mouse model of human CYP3A4 regulation, we have generated transgenic
      mice carrying constructs comprising the upstream regulatory region of the human
      CYP3A4 gene linked to the lacZ reporter gene. Constitutive expression was
      observed in a developmental, tissue- and cell-specific fashion that mirrors the
      human situation. In addition, robust hepatic and intestinal induction with a
      range of reagents known to activate PXR and/or CAR (e.g., dexamethasone,
      pregnenolone 16alpha-carbonitrile, and phenobarbital) was observed. However, no
      expression or induction was apparent with a construct lacking upstream sequences
      beyond - 3.2 kilobases. Histochemical staining for beta-galactosidase activity
      revealed that dose-dependent increases in transgene levels were associated with a
      zonal expansion of lacZ expressing hepatocytes, suggesting that xenobiotic
      induction of CYP3A genes operates primarily through the recruitment of more cells
      committed to expression. In summary, CYP3A4/lacZ transgenic mice provide an in
      vivo model for the study of the molecular mechanisms involved in the regulation
      of a significant human drug metabolizing enzyme.

PMID- 12815160
TI  - Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.
AB  - Taxanes act by inhibiting microtubule dynamics; in this study, we have
      investigated mitochondria as an additional target of taxanes. We incubated
      isolated mitochondria in the presence of taxanes with or without stimulation of
      the mitochondrial respiratory state. Results showed that they rapidly induced the
      loss of deltapsim after stimulation of the respiratory state. To evaluate the
      binding of [14C]paclitaxel to isolated mitochondria, mitochondrial proteins were
      precipitated yielding 18.6 +/- 2.1 cpm/microg of protein. After stimulation of
      the respiratory state, binding of [14C]paclitaxel increased up to 163.2 +/- 46.7
      cpm/microg of protein. CPM values after Bcl-2 immunoprecipitation was 62.8-fold
      higher than those of the control antibody, thereby indicating the involvement of
      Bcl-2 in paclitaxel binding. Then, we established a panel of A2780 cell lines
      resistant to increasing doses of paclitaxel alone or to high doses of
      paclitaxel/cyclosporin A (A2780 TC cells). In both cases, Bcl-2 expression was
      consistently down-regulated, whereas levels of other members of the Bcl-2 family,
      such as Bax and Bcl-x, did not change in paclitaxel-resistant cell lines. When
      A2780TC cells were stably transfected with a Bcl-2 construct, paclitaxel
      sensitivity was partially restored, thereby supporting a direct role of Bcl-2
      down-regulation in the maintenance of drug-resistance. Finally, we examined Bcl-2
      by immunohistochemistry in a small subset of ovarian cancer paclitaxel-resistant
      patients and we noticed that the protein is down-regulated in this clinical
      setting with respect to the expression levels found in drug-sensitive tumors.
      These findings demonstrate that Bcl-2 is an additional intracellular target of
      taxanes and that its down-regulation is involved in taxane resistance.

PMID- 12815161
TI  - APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks
      voltage-gated human ether-a-go-go-related gene potassium channels.
AB  - A new peptide, APETx1, which specifically inhibits human ether-a-go-go-related
      gene (HERG) channels, was purified from venom of the sea anemone Anthopleura
      elegantissima. APETx1 is a 42-amino acid peptide cross-linked by three disulfide
      bridges and shares 54% homology with BDS-I, another sea anemone K+ channel
      inhibitor. Although they differ in their specific targets, circular dichroism
      spectra and molecular modeling indicate that APETx1 and BDS-I have a common
      molecular scaffold and belong to the same structural family of K+ channel
      blocking peptides. APETx1 inhibits HERG currents in a heterologous system with an
      IC50 value of 34 nM by modifying the voltage dependence of the channel gating.
      Central injections in mice failed to induce any neurotoxic symptoms. APETx1,
      which has no sequence homologies with scorpion toxins acting on HERG, defines a
      new structural group of HERG gating modifiers isolated from a sea anemone.

PMID- 12815162
TI  - Molecular determinants of KCNQ1 channel block by a benzodiazepine.
AB  - KCNQ1 channels underlie the slow delayed rectifier K+ current, mediate
      repolarization of cardiac action potentials, and are a potential therapeutic
      target for treatment of arrhythmia. (E)-(+)-N-[(3R)-2,3-dihydro-1-methyl-2-oxo-5
      phenyl-1H-1,4-benzodiazepin-3-yl]-3-(2,4-dichlorophenyl)-2-propenamide [L-735821
      (L-7)] is a potent blocker of KCNQ1 channels. Here we describe the structural
      determinants of KCNQ1 that are critical for high-affinity block by L-7 using site
      directed mutagenesis to alter specific residues and voltage clamp to record
      channel currents in Xenopus laevis oocytes. Chimeric channels were constructed by
      combination of regions from L-7-sensitive KCNQ1 and L-7-insensitive KCNQ2 channel
      subunits. This approach localized the drug interaction site to the pore and S6
      domains of KCNQ1. Substitution of single amino acids identified Thr-312 of the
      pore domain and Ile-337, Phe-339, Phe-340, and Ala-344 of the S6 domain as the
      most important molecular determinants of channel block. Some mutations also
      altered the inactivation properties of KCNQ1, but there was no correlation
      between extent of inactivation and sensitivity to block by L-7. Modeling was used
      to simulate the docking of L-7 to the KCNQ1 channel pore. The docking was
      consistent with our experimental data and predicts that L-7 blocks K+ conductance
      by physically precluding the occupancy of a K+ ion to a pore helix-coordinated
      site within the central hydrated cavity, a crucial step in ion permeation.

PMID- 12815163
TI  - Positive allosteric modulator of the human 5-HT2C receptor.
AB  - The human 5-hydroxytryptamine-2C (5-HT2C) receptor has been the target of
      potential anxiolytics and antiobesity drugs, and its positive allosteric
      modulator was discovered to be l-threo-alpha-d-galacto-octopyranoside, methyl-7
      chloro-6,7,8-trideoxy-6-[[(4-undecyl-2-piperidinyl)carbonyl]amino]-1
      thiomonohydrochloride (2S-cis) (PNU-69176E). The drug at low micromolar
      concentrations (<25 microM) markedly enhanced [3H]5-HT binding (more than 300%)
      by increasing its affinity for low-affinity sites but with no appreciable effect
      on antagonist ([3H]mesulergine) binding. Functionally, PNU-69176E alone rendered
      receptors constitutively active, producing the pheno-types of 5-HT-activated
      receptors, as measured with mesulergine-sensitive guanosine 5'-O-(3
      [35S]thio)triphosphate binding, transient inositol 1,4,5-triphosphate release,
      and [3H]inositol phosphate accumulation. These actions of PNU-69176E were
      observed with the human 5-HT2C receptor expressed in several mammalian cell lines
      (human embryonic kidney 293, NIH3T3, and SH-EP) at variable receptor densities (6
      to 45 pmol/mg of protein), but not with analogous 5-HT and dopamine receptors
      (human 5-HT2A, 5-HT2B, 5-HT6, 5-HT7, and dopamine D2-long and D3 receptors).
      Structurally, PNU-69176E consists of a long alkyl chain and a polar moiety,
      including the alpha-d-galactopyranoside. Its analogs with shorter alkyl chains
      (methyl to n-hexyl instead of n-undecyl group) failed to enhance [3H]5-HT
      binding, and also long alkyl amides are without allosteric modulation. We propose
      that PNU-69176E may represent a new class of membrane receptor modulators, which
      probably need a long alkyl chain as a membrane anchor and target a selective
      polar head group to receptor modulatory sites near the membrane surface.

PMID- 12815164
TI  - Anti-inflammatory activity of 15-deoxy-delta12,14-PGJ2 and 2-cyclopenten-1-one:
      role of the heat shock response.
AB  - The transcription factor heat shock factor 1 (HSF1) plays a key role in the
      expression of several genes, such as heat shock protein (hsp) genes, which are
      cytoprotective against several pathological conditions, including inflammation.
      Cyclopentenone prostaglandins (cyPG) are able to activate HSF1 and induce the
      synthesis of the 70-kDa hsp (hsp70) in mammalian cells. These molecules are
      characterized by the presence of a reactive alpha,beta-unsatured carbonyl group
      in the cyclopentane ring (cyclopentenone) which is the key structure for
      triggering HSF1 activation. In the present study, we investigated, in carrageenin
      hind-paw edema, an acute model of inflammation, the effect of double-stranded
      oligodeoxynucleotides with consensus HSF1 sequence as transcription factor decoys
      to inhibit HSF1 binding to native DNA sites. We show that HSF1 activation and
      hsp72 expression occurs in inflamed tissue and that this effect is associated
      with the remission of the inflammatory reaction. Moreover, we studied the effect
      of prostaglandin 15-deoxy-delta12,14-prostaglandin (PG) J2, of its precursor,
      PGD2 and, for the first time in vivo, the effect of the cyclopentenone ring
      structure itself, 2-cyclopenten-1-one. Our results demonstrated that all agents
      used had anti-inflammatory properties and that this effect was associated with
      HSF1-induced hsp72 expression in vivo, suggesting that the use of cyclopentenone
      derivatives may represent a novel therapeutic approach to the treatment of
      inflammatory diseases.

PMID- 12815165
TI  - Molecular determination of agouti-related protein binding to human melanocortin-4
      receptor.
AB  - Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin-4
      receptor (MC4R) that functions in the hypothalamic control of feeding behavior.
      Our previous studies have suggested that in addition to exoloops 2 and 3, several
      transmembrane domains of MC4R may be important for AGRP binding. However, the
      detailed molecular basis of MC4R domains in AGRP binding is presently unclear.
      The present studies were designed to determine the specific contribution of MC4R
      exoloops and transmembrane domains to AGRP binding by using chimeric receptor
      constructs of the human melanocortin-1 receptor (hMC1R), a receptor that is not
      inhibited by AGRP, and the human MC4R (hMC4R), a receptor that is potently
      inhibited by AGRP. Our results indicate that substitutions of the second and
      third extracellular loops of the MC4R with homologous domains of the MC1R
      dramatically decreased AGRP 87-132 binding affinity, but did not affect AGRP 110
      117 binding affinity. In contrast, cassette substitutions of the third or fourth
      transmembrane domain of the MC4R with the homologous domain of the MC1R resulted
      in a substantial decrease of AGRP 87-132 binding affinity and loss of AGRP 110
      117 binding affinity. These data suggest that the AGRP fragment 110-117 has no
      binding sites at exoloops of hMC4R and that transmembrane domains of MC4R may
      play an important role in AGRP 110-117 binding and function, whereas the exoloops
      do not. The second and third extracellular loops of MC4R are important for AGRP
      87-132 N-terminal binding, whereas the third and fourth transmembrane domains of
      hMC4R are crucial for AGRP 110-117 binding.

PMID- 12815166
TI  - Pharmacological characterization of the human P2Y13 receptor.
AB  - The P2Y13 receptor has recently been identified as a new P2Y receptor sharing a
      high sequence homology with the P2Y12 receptor as well as similar functional
      properties: coupling to Gi and responsiveness to ADP (Communi et al., 2001). In
      the present study, the pharmacology of the P2Y13 receptor and its differences
      with that of the P2Y12 receptor have been further characterized in 1321N1 cells
      (binding of [33P]2-methylthio-ADP (2MeSADP) and of GTPgamma[35S]), 1321N1 cells
      coexpressing Galpha16 [AG32 cells: inositol trisphosphate (IP3) measurement,
      binding of GTPgamma[35S]) and Chinese hamster ovary (CHO)-K1 cells (cAMP assay)].
      2MeSADP was more potent than ADP in displacing [33P]2MeSADP bound to 1321N1 cells
      and increasing GTPgamma[35S] binding to membranes prepared from the same cells.
      Similarly, 2MeSADP was more potent than ADP in stimulating IP3 accumulation after
      10 min in AG32 cells and increasing cAMP in pertussis toxin-treated CHO-K1 cells
      stimulated by forskolin. On the other hand, ADP and 2MeSADP were equipotent at
      stimulating IP3 formation in AG32 cells after 30 s and inhibiting
      forskolininduced cAMP accumulation in CHO-K1 cells. These differences in potency
      cannot be explained by differences in degradation rate, which in AG32 cells was
      similar for the two nucleotides. When contaminating diphosphates were
      enzymatically removed and assay of IP3 was performed after 30 s, ATP and 2MeSATP
      seemed to be weak partial agonists of the P2Y13 receptor expressed in AG32 cells.
      The stimulatory effect of ADP on the P2Y13 receptor in AG32 cells was antagonized
      by reactive blue 2, suramin, pyridoxal-phosphate-6-azophenyl-2',4'disulfonic
      acid, diadenosine tetraphosphate, and 2-(propylthio)-5'-adenylic acid,
      monoanhydride with dichloromethylenebis (phosphonic acid) (AR-C67085MX), but not
      by N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate (MRS-2179) (up to 100 microM).
      The most potent antagonist was N6-(2-methylthioethyl)-2-(3,3,3
      trifluoropropylthio)-5'-adenylic acid, monoanhydride with dichloromethylenebis
      (phosphonic acid) (ARC69931MX) (IC50 = 4 nM), which behaved in a noncompetitive
      way. The active metabolite of clopidogrel was unable to displace bound 2MeSADP at
      concentrations up to 2 microM.

PMID- 12815167
TI  - Regulation of CYP2C11 by dehydroepiandrosterone and peroxisome proliferators:
      identification of the negative regulatory region of the gene.
AB  - Treatment of rats with peroxisome proliferators is known to affect gene
      expression, including suppression of CYP2C11. The current study examined the
      mechanism of negative regulation of CYP2C11, comparing the effects of a classic
      peroxisome proliferator, nafenopin, with those of the steroid
      dehydroepiandrosterone (DHEA). In vivo dose-response experiments for DHEA were
      carried out with rats. Only the highest dose of DHEA in the diet (0.45%), a dose
      previously shown to produce peroxisome proliferation, caused suppression of
      CYP2C11 expression. Lower doses of DHEA (0.012 to 0.20% in diet) had little
      effect on CYP2C11 expression. In HepG2 cells, negative regulation of a CYP2C11
      reporter gene by nafenopin required coexpression of PPARalpha, whereas negative
      regulation by DHEA did not. Deletion analysis revealed that the responsive region
      for both DHEA and nafenopin was between -108 and -60 relative to the
      transcription start site. Mutations in several putative transcription factor
      binding sites in the 5'-flanking region of CYP2C11 were produced. A mutation at 
      121 bp significantly diminished basal expression of CYP2C11 but did not affect
      negative regulation by DHEA or nafenopin. A mutation at -75 bp had only a small
      effect on basal expression but completely abolished negative regulation by DHEA
      and nafenopin. Gel shift experiments indicated that PPARalpha/RXRalpha
      heterodimers do not bind DNA in this region. Therefore, the sequence at -75 bp of
      CYP2C11 is necessary for negative regulation by both DHEA and nafenopin. However,
      the upstream events leading to suppression at this site must differ for DHEA and
      nafenopin.

PMID- 12815168
TI  - Jesterone dimer, a synthetic derivative of the fungal metabolite jesterone,
      blocks activation of transcription factor nuclear factor kappaB by inhibiting the
      inhibitor of kappaB kinase.
AB  - Rel/nuclear factor-kappaB (NF-kappaB) transcription factors control a variety of
      cellular processes, such as cell growth and apoptosis, and are continually
      activated in many human diseases, including chronic inflammatory diseases and
      cancer. Jesterone dimer (JD) is a synthetic derivative of the natural fungal
      metabolite jesterone, and JD has previously been shown to be cytotoxic in select
      tumor cell lines. In this report, we demonstrate that JD is a potent inhibitor of
      the activation of transcription factor NF-kappaB. Namely, JD inhibits tumor
      necrosis factor-alpha-induced activation of NF-kappaB in mouse 3T3 and human HeLa
      cells. JD seems to block the induction of the NF-kappaB pathway by inhibiting the
      inhibitor of kappaB kinase (IKK); that is, treatment of cells with JD blocks
      phosphorylation of IkappaBalpha, inhibits the activity of a constitutively active
      form of the IKKbetacatalytic subunit, and converts IKKbetato stable high
      molecular mass forms. Like JD, a JD-related epoxyquinoid (isotorreyanic acid)
      inhibits activation of NF-kappaB at 20 microM, whereas several other
      epoxyquinoids that are related to JD, including its parent compound jesterone, do
      not block activation of NF-kappaB at this concentration. Finally, JD inhibits
      both proliferation and DNA binding by REL-containing complexes in the human
      lymphoma SUDHL-4 cell line, and JD activates caspase-3 activity in these cells.
      In summary, these results suggest that JD induces apoptosis in tumor cells
      through a mechanism that involves the inhibition of Rel/NF-kappaB activity and
      demonstrate the usefulness of assessing the bioactivity of synthetic derivatives
      of natural products.

PMID- 12815169
TI  - Corticotropin induces the expression of TREK-1 mRNA and K+ current in
      adrenocortical cells.
AB  - Bovine adrenal zona fasciculata (AZF) cells express a two-pore/four-transmembrane
      segment bTREK-1 K+ channel that sets the resting potential and couples hormonal
      signals to depolarization-dependent Ca2+ entry and cortisol secretion. It was
      discovered that corticotropin (1-2000 pM) enhances the expression of bTREK-1 mRNA
      and membrane current in cultured AZF cells. Forskolin and 8-pcpt-cAMP mimicked
      corticotropin induction of bTREK-1 mRNA, but angiotensin II (AII) was
      ineffective. The induction of bTREK-1 mRNA by corticotropin was partially blocked
      by the A-kinase antagonist H-89. 8-(4-Chloro-phenylthio)-2-O-methyladenosine-3'
      5'-cyclic monophosphate, a cAMP analog that activates cAMP-regulated guanine
      nucleotide exchange factors (Epac), failed to increase bTREK-1 mRNA.
      Corticotropin-stimulated increases in bTREK-1 mRNA were eliminated by inhibitors
      of protein synthesis or gene transcription. bTREK-1 current disappeared after 24
      h in serum-supplemented medium, but in the presence of corticotropin, bTREK-1
      expression was maintained for at least 48 h. The enhancement of bTREK-1 mRNA and
      ionic current contrasts with the corticotropin-induced down-regulation of the
      Kv1.4 voltage-gated K+ current and associated mRNA in AZF cells. These results
      demonstrate that corticotropin rapidly and potently induces the expression of
      bTREK-1 in AZF cells at the pretranslational level by a cAMP-dependent mechanism
      that is partially dependent on A-kinase but independent of Epac and Ca2+. They
      further indicate that prolonged stimulation of AZF cells by corticotropin, as
      occurs during long-term stress or disease, may produce pronounced changes in the
      expression of genes encoding ion channels, thereby reshaping the electrical
      properties of these cells to enhance or limit cortisol secretion.

PMID- 12815170
TI  - [125I]A-312110, a novel high-affinity 1,4-dihydropyridine ATP-sensitive K+
      channel opener: characterization and pharmacology of binding.
AB  - Although ATP-sensitive K+ channels continue to be explored for their therapeutic
      potential, developments in high-affinity radioligands to investigate native and
      recombinant KATP channels have been less forthcoming. This study reports the
      identification and pharmacological characterization of a novel iodinated 1,4
      dihydropyridine KATP channel opener, [125I]A-312110 [(9R)-9-(4-fluoro-3
      125iodophenyl)-2,3,5,9-tetrahydro-4H-pyrano[3,4-b]thieno[2,3-e]pyridin-8(7H)-one
      1,1-dioxide]. Binding of [125I]A-312110 to guinea pig cardiac (KD = 5.8 nM) and
      urinary bladder (KD = 4.9 nM) membranes were of high affinity, saturable, and to
      a single set of binding sites. Displacement of [125I]A-312110 by structurally
      diverse potassium channel openers (KCOs) indicated a similar rank order of
      potency in both guinea pig cardiac and bladder membranes (Ki, heart): A-312110
      (4.3 nM) > N-cyano-N'-(1,1-dimethylpropyl)-N"-3-pyridylguanidine (P1075) > (-)-N
      (2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2-nitroethene-1,1-diamine (Bay X
      9228) > pinacidil > (-)-cromakalim > N-(4-benzoyl phenyl)-3,3,3-trifluro-2
      hydroxy-2-methylpropionamine (ZD6169) > 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro
      1,8-(2H,5H)-acridinedione (ZM244085) >> diazoxide (16.7 microM). Displacement by
      KATP channel blockers, the sulfonylurea glyburide, and the cyanoguanidine N-[1-(3
      chlorophenyl)cyclobutyl]-N'-cyano-N"-3-pyridinyl-guanidine (PNU-99963) were
      biphasic in the heart but monophasic in bladder with about a 100- to 500-fold
      difference in Ki values between high- and low-affinity sites. Good correlations
      were observed between cardiac or bladder-binding affinities of KCOs with
      functional activation as assessed by their respective potencies to either
      suppress action potential duration (APD) in Purkinje fibers or to relax
      electrical field-stimulated bladder contractions. Collectively, these results
      demonstrate that [125I]A-312110 binds with high affinity and has an improved
      activity profile compared with other radiolabeled KCOs. [125I]A-312110 is a
      useful tool for investigation of the molecular and functional properties of the
      KATP channel complex and for the identification, in a high throughput manner, of
      both novel channel blockers and openers that interact with cardiac/smooth muscle
      type KATP channels.

PMID- 12815171
TI  - Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions.
AB  - Phenobarbital (PB) treatment impairs the biliary excretion of some organic
      anions. One mechanism may involve direct competition for biliary excretion by PB
      and/or a PB metabolite. Alternatively, PB may alter the expression and/or
      function of hepatic organic anion transport proteins. The role of multidrug
      resistance-associated protein 2 (Mrp2) in the biliary excretion of PB and
      metabolites was studied using isolated perfused livers (IPLs) from Wistar and
      Mrp2-deficient TR- rats. In normal livers, 4.19 +/- 0.53% of the PB dose was
      recovered in bile as PB metabolites [2.21 +/- 0.69% as 5-ethyl-5-(4-OH phenyl)
      barbituric acid (PBOH)-glucuronide; 1.98 +/- 0.09% as PBOH-sulfate]. In TR-
      livers, only PBOH-sulfate was recovered in bile (0.35 +/- 0.16% of dose) during
      the 2-h perfusion. Mrp2 message was increased (2.3-fold) by PB pretreatment (80
      mg/kg i.p. x 4 days) but decreased to control values after a 48-h washout. Mrp2
      protein was increased slightly in PB-treated livers and remained slightly
      elevated after a 24-h washout, but it was decreased significantly to 62 +/-7% of
      control values after a 48-h washout. The 120-min cumulative biliary excretion of
      the Mrp2 substrate 5-(and-6)-carboxy-2', 7'-dichlorofluorescein in IPLs from PB
      treated rats after a 48-h washout was significantly lower than in vehicle-treated
      livers (66.3 +/- 9.2% versus 83.4 +/- 2.4% of the dose, respectively). These data
      support two mechanisms for impaired biliary excretion of some organic anions by
      PB treatment: 1) PBOH-glucuronide is a substrate for Mrp2 and may compete with
      other organic anions for biliary excretion and 2) Mrp2 protein expression and
      functional capacity is decreased 48 h after PB treatment.

PMID- 12815172
TI  - Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human
      hepatocytes by affecting their glucocorticoid receptor-mediated regulation.
AB  - The xenobiotic-mediated induction of three major human liver cytochrome P450
      genes, CYP2B6, CYP2C9, and CYP3A4, is known to be regulated by the constitutive
      androstane receptor (CAR) and the pregnane X receptor (PXR). CAR and PXR are
      regulated, at least in part, by the glucocorticoid receptor (GR) and the
      hypothesis of a signal transduction cascade GR-[CAR/PXR]-P450 has been proposed.
      This study was aimed at testing this hypothesis in primary human hepatocytes by
      using the tubulin network disrupting agent colchicine. Colchicine (COL) decreased
      both basal and rifampicin- and phenobarbital-inducible expression of CYP2B6,
      CYP2C8/9, and CYP3A4. A parallel down-regulation of mRNA expression of CAR, PXR,
      and tyrosine aminotransferase, a prototypic gene directly regulated by GR, was
      observed. COL affected neither the level of GR mRNA nor ligand binding to GR. To
      evaluate the effect of colchicine on GR-mediated gene transactivation, HeLa cells
      stably or transiently transfected with a GR-responsive element-dependent
      luciferase reporter gene were used. COL decreased the dexamethasone-induced
      luciferase expression in stably transfected cell line by 50%, whereas GR
      transactivation in transiently transfected cells was not affected by COL. In
      contrast, ligand-dependent GR translocation in the human embryonic kidney 293
      cell line transiently transfected with GFP-GR was inhibited by COL. We conclude
      that alteration of the signal transduction mediated through the GR-[CAR/PXR]-P450
      cascade by colchicine is responsible for the down-regulation of CYP2C9 and
      CYP3A4, implicating cytoskeleton as necessary for correct functioning of this
      cascade under physiological conditions.

PMID- 12815173
TI  - Generation and functional characterization of arylamine N-acetyltransferase
      Nat1/Nat2 double-knockout mice.
AB  - Arylamine N-acetyltransferases (NATs) catalyze the biotransformation of a variety
      of arylamine drugs and carcinogens and may play diametrically opposing roles in
      enhancing either the detoxification of these chemicals or their metabolic
      activation into DNA-binding electrophiles. To facilitate the study of these
      processes, we have generated a Nat1/Nat2 double-knockout mouse model by gene
      targeting in embryonic stem cells. Nat1/2(-/-) mice were born at the expected
      frequency and seemed normal and viable with no overt phenotype, indicating that
      these genes are not critical for development or physiological homeostasis. In
      wild-type mice, NAT1 and NAT2 transcripts were detectable by RT-PCR in all
      tissues assayed including liver, kidney, colon, brain, bladder, and spleen. NAT1
      and NAT2 transcripts were completely undetectable in the Nat1/2(-/-) mice. The in
      vitro N-acetylation of p-aminosalicylate was detected at significant levels in
      liver and kidney cytosols from either wild-type inbred 'rapid acetylator' C57BL/6
      mice or from outbred CD-1 mice possessing homozygous rapid, heterozygous, or
      homozygous 'slow acetylator' Nat2 genotypes. Activity was undetectable in cytosol
      preparations from Nat1/2(-/-) mice. Nat1/2(-/-) mice also displayed severely
      compromised in vivo pharmacokinetics of p-aminosalicylate (PAS) and
      sulfamethazine (SMZ), with a drastically increased plasma area under the curve
      for PAS and a complete absence of their acetylated metabolites (AcPAS or AcSMZ)
      from plasma, confirming the functional absence of these enzymes and impaired drug
      metabolism capacity. This knockout mouse model should be helpful in delineating
      the role that variation in acetylating enzymes plays in mediating interindividual
      differences in susceptibility to arylamine-induced chemical toxicity and/or
      carcinogenesis.

PMID- 12815174
TI  - Interactions of orthosteric and allosteric ligands with [3H]dimethyl-W84 at the
      common allosteric site of muscarinic M2 receptors.
AB  - An optimized assay for the binding of [3H]dimethyl-W84 to its allosteric site on
      M2 muscarinic receptors has been used to directly measure the affinities of
      allosteric ligands. Their potencies agree with those deduced indirectly by their
      modulation of the equilibrium binding and kinetics of [3H]N-methylscopolamine
      ([3H]NMS) binding to the orthosteric site. The affinities and cooperativities of
      orthosteric antagonists with [3H]dimethyl-W84 have also been quantitated. These
      affinities agree with those measured directly in a competition assay using
      [3H]NMS. All these data are compatible with the predictions of the allosteric
      ternary complex model. The association and dissociation kinetics of [3H]dimethyl
      W84 are rapid but the estimate of its association rate constant is nevertheless
      comparable with that found for the orthosteric radioligand, [3H]NMS. This is
      unexpected, given that the allosteric site to which [3H]dimethyl-W84 binds is
      thought to be located on the external face of the receptor and above the [3H]NMS
      binding site that is buried within the transmembrane helices. The atypical
      allosteric ligands tacrine and 4,4'-bis-[(2,6-dichloro-benzyloxy-imino)-methyl]
      1,1'-propane-1,3-diyl-bis-pyridinium dibromide (Duo3) inhibit [3H]dimethyl-W84
      binding with the same potencies and comparably steep slope factors as found for
      inhibition of [3H]NMS binding. Tacrine and Duo3 decrease [3H]dimethyl-W84
      affinity, not the number of binding sites. It is suggested that these atypical
      ligands either bind to the two known spatially separated allosteric sites on
      muscarinic receptors with positive cooperativity or their binding to the common
      allosteric site modulates receptor-receptor interactions such that homotropic
      positive cooperativity within a dimer or higher oligomer is generated.

PMID- 12815175
TI  - Inhibition of small-conductance Cl- channels by the interleukin-1beta-stimulated
      production of superoxide in rabbit gastric parietal cells.
AB  - We have shown previously that the G protein-coupled production of superoxide
      anion (O2-) leads to closure of small-conductance Cl- channels (0.3-0.4 pS) in
      the basolateral membrane of rabbit parietal cells. In the present study, effects
      of interleukin-1beta (IL-1beta) on the Cl- channel were investigated. In the
      whole-cell patch-clamp recording, IL-1beta (0.3-10 ng ml-1) inhibited the whole
      cell Cl- current recorded from a parietal cell within isolated rabbit gastric
      glands. Variance noise analysis of the whole-cell Cl- current showed that the
      single channel conductance of the Cl- channel that is sensitive to IL-1beta is
      0.37 pS. The IL-1beta (1 ng ml-1)-induced decrease of the Cl- current was
      abolished by anti-IL-1beta antibody (2 microg ml-1), recombinant IL-1 receptor
      antagonist (500 ng ml-1), GDPbetaS (500 microM) and superoxide dismutase (100
      units ml-1), a scavenger of O2-. Northern blot analysis showed that the mRNA of
      the IL-1 receptor was selectively expressed in rabbit gastric parietal cells. In
      the dihydrofluorescein diacetate-loaded single parietal cells in gastric glands,
      IL-1beta (0.3-10 ng ml-1) stimulated the production of oxygen radicals. Y-27632
      (1-10 microM), a specific Rho-kinase inhibitor, and fluvastatin (10 microM), an
      indirect inhibitor for Rho proteins, significantly inhibited the IL-1beta-induced
      effects on the channel activity and production of oxygen radicals. IL-1beta (0.3
      10 ng ml-1) activated Rho in the parietal cells. These results indicate that IL
      1beta binds to the IL-1 receptor of gastric parietal cells and inhibits the small
      conductance Cl- channel via the G protein-mediated Rho/Rho-kinase-dependent
      production of O2-.

PMID- 12815176
TI  - G protein-independent inhibition of GIRK current by adenosine in rat atrial
      myocytes overexpressing A1 receptors after adenovirus-mediated gene transfer.
AB  - G protein-activated inwardly rectifying K+ (GIRK) channels, important regulators
      of membrane excitability in the heart and central nervous system, are activated
      by interaction with betagamma subunits from heterotrimeric G proteins upon
      receptor stimulation. In atrial myocytes various endogenous receptors couple to
      GIRK channels, including the canonical muscarinic M2 receptor (M2AChR) and the A1
      adenosine receptor (A1AdoR). Saturating stimulation of A1AdoR in atrial myocytes
      activates only a fraction of the GIRK current that is activated via M2AChR, which
      reflects a lower density of A1AdoR. In the present study A1AdoR were
      overexpressed by means of adenovirus-mediated gene transfer using green
      fluorescent protein (GFP) as the reporter. Confirmatory to a previous study, this
      resulted in an increased sensitivity of macroscopic GIRK current (ACh-activated
      K+ current (IK(ACh))) to stimulation by Ado. However, in the majority of GFP
      positive myocytes, exposure to Ado at concentrations > or =1 microM resulted in
      activation of IK(ACh) followed by a rapid inhibition. In those cells a rebound
      activation of current was recorded upon washout of Ado. The inhibitory component
      could be recorded in isolation when IK(ACh) was activated by M2AChR-stimulation
      and brief pulses of Ado were superimposed. In myocytes loaded with GTP-gamma-S,
      IK(ACh), irreversibly activated by brief exposure to agonist, was still
      reversibly inhibited by Ado, suggesting that inhibition is independent of G
      protein cycling. In myocytes co-transfected with adenoviral vectors encoding
      A1AdoR and GIRK4 subunit, no inhibition of GIRK current by Ado was observed. As
      acute desensitization of atrial GIRK current, which is reminiscent of the
      inhibition described here, has been shown to be absent in myocytes overexpressing
      GIRK4, this suggests that acute desensitization and the novel inhibition might
      share a common pathway whose target is the GIRK channel complex or its GIRK1
      subunit.

PMID- 12815177
TI  - Sacral dorsal horn neurone activity during micturition in the cat.
AB  - The excitability of two groups of neurones located in different parts of the
      sacral spinal cord were examined during micturition in decerebrate adult cats.
      One group of cells, characterized by their activation by pudendal cutaneous
      afferents, was located in the dorsal commissure of the first and second sacral
      spinal segments. The second group, located in the dorsal horn of the first sacral
      spinal segment, was excited by group II muscle and cutaneous afferents.
      Micturition was evoked by distension of the urinary bladder or by electrical
      stimulation of the pontine micturition centre. Tonic firing was induced in the
      neurones by ejection of DL-homocysteic acid from the recording extracellular
      micropipette. The instantaneous firing frequency of 11/17 sacral dorsal grey
      commissure neurones was decreased from 7 to 100 % during micturition, and on
      average was about half of the prevoid firing frequency. It is hypothesized that
      these sacral neurones are interposed in polysynaptic excitatory pathways from
      sacral perineal afferents to sphincter motoneurones and that they are subject to
      direct postsynaptic inhibition during micturition. One other cell showed no
      change in firing during micturition, two displayed complex patterns of
      modulation, while 3/17 of the dorsal grey commissure neurones increased their
      firing rate 30 to 1000 % during micturition. It is hypothesized that the excited
      neurones may be part of the inhibitory pathways mediating postsynaptic inhibition
      of sphincter motoneurones or sacral primary afferent depolarization during
      micturition. Alternatively, they may be part of the excitatory urethral-bladder
      reflex circuitry. A small (5-15 %) but significant decrease in firing was
      observed in 4/5 of the group II rostral sacral neurones examined; the firing of a
      fifth neurone was unchanged. The depression of group II neurones may serve to
      suppress unwanted hindlimb reflexes that could disrupt micturition.

PMID- 12815178
TI  - Mitochondrial and myoplasmic [Ca2+] in single fibres from mouse limb muscles
      during repeated tetanic contractions.
AB  - Previous studies on single fast-twitch fibres from mouse toe muscles have shown
      marked fatigue-induced changes in the free myoplasmic [Ca2+] ([Ca2+]i), while
      mitochondrial [Ca2+] remained unchanged. We have now investigated whether muscle
      fibres from the legs of mice respond in a similar way. Intact, single fibres were
      dissected from the soleus and extensor digitorum longus (EDL) muscles of adult
      mice. To measure [Ca2+]i, indo-1 was injected into the isolated fibres.
      Mitochondrial [Ca2+] was measured using Rhod-2 and confocal laser microscopy.
      Fatigue was induced by up to 1000 tetanic contractions (70 Hz) given at 2 s
      intervals. In soleus fibres, there was no significant decrease in tetanic [Ca2+]i
      at the end of the fatiguing stimulation, whereas tetanic force was significantly
      reduced by about 30 %. In 10 out of 14 soleus fibres loaded with Rhod-2 and
      subjected to fatigue, mitochondrial [Ca2+] increased to a maximum after about 50
      tetani; this increase was fully reversed within 20 min after the end of
      stimulation. The force-frequency curve of the non-responding soleus fibres was
      shifted to higher frequencies compared to that of the responding fibres. In
      addition, eight out of nine Rhod-2-loaded EDL fibres showed similar changes in
      mitochondrial [Ca2+] during and after a period of fatiguing stimulation. The
      stimulation-induced increase in mitochondrial [Ca2+] was reduced when
      mitochondria were depolarised by application of carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone, whereas it was increased by application of an
      inhibitor of the mitochondrial Na+/Ca2+ exchange (CGP-37157). In conclusion,
      isolated slow-twitch muscle fibres show only modest changes in tetanic force and
      [Ca2+]i during repeated contractions. The increase in mitochondrial Ca2+ does not
      appear to be essential for activation of mitochondrial ATP production, nor does
      it cause muscle damage.

PMID- 12815179
TI  - Acute and chronic effects of oestrogen on endothelial tissue-type plasminogen
      activator release in postmenopausal women.
AB  - The capacity of vascular endothelium to locally release tissue-type plasminogen
      activator (t-PA) represents an important endogenous defence mechanism against
      intravascular fibrin deposition and thrombosis. We determined the influence of
      chronic and acute oestrogen administration on endothelial t-PA release in
      postmenopausal women. Sixty-three healthy postmenopausal women were studied: 31
      non-users (age 58 +/- 1 years) and 32 users of hormone replacement therapy,
      including oestrogen alone (ORT: 62 +/- 2 years; n = 15) and in combination with
      progesterone (HRT: 57 +/- 1 years; n = 17). Net endothelial t-PA release was
      determined in vivo, in response to intrabrachial infusions of bradykinin and
      sodium nitroprusside. To examine the acute effects of oestrogen on endothelial t
      PA release, bradykinin and sodium nitroprusside dose-response curves were
      repeated in the presence of 17 beta-oestradiol in 20 of the 31 non-users. Net
      endothelial release of t-PA was ~30 % higher (P < 0.01) in women taking ORT (from
      2.0 +/- 1.0 to 83.6 +/- 9.2 ng (100 ml tissue)-1 min-1) compared with those
      taking HRT (from 1.4 +/- 0.4 to 63.5 +/- 5.6 ng (100 ml tissue)-1 min-1) and
      those not taking supplementation (1.0 +/- 0.7 to 63.0 +/- 4.7 ng (100 ml tissue)
      1 min-1). Intra-arterial infusion of 17 beta-oestradiol significantly potentiated
      bradykinin-induced t-PA release. Net endothelial release of t-PA was
      approximately 45 % higher (P < 0.01) after (from 1.0 +/- 0.8 to 87.4 +/- 9.9 ng
      (100 ml tissue)-1 min-1) versus before (1.2 +/- 0.6 to 60.8 +/- 5.6 ng (100 ml
      tissue)-1 min-1) acute 17 beta-oestradiol administration. Our results suggest
      that oestrogen has a direct modulatory effect on the capacity of the endothelium
      to release t-PA in healthy postmenopausal women. However, progesterone appears to
      oppose the favourable influence of oestrogen on endothelial fibrinolytic
      capacity.

PMID- 12815180
TI  - Role of cyclic nucleotide phosphodiesterase isoforms in cAMP compartmentation
      following beta2-adrenergic stimulation of ICa,L in frog ventricular myocytes.
AB  - The role of cyclic nucleotide phosphodiesterase (PDE) isoforms in the beta2
      adrenergic stimulation of the L-type Ca2+ current (ICa,L) was investigated in
      frog ventricular myocytes using double patch-clamp and double-barrelled
      microperfusion techniques. Isoprenaline (ISO, 1 nM to 10 microM) was applied on
      one half of the cell, either alone or in the presence of PDE inhibitors, and the
      local and distant responses of ICa,L were used to determine the gradient of local
      vs. distant cAMP concentration (alpha). IBMX (100 microM), a non-selective PDE
      inhibitor, reduced alpha from 40 to 4.4 indicating a 9-fold reduction in
      intracellular cAMP compartmentation when all PDE activity was blocked. While PDE1
      and PDE2 inhibition had no effect, PDE3 inhibition by milrinone (3 microM) or
      PDE4 inhibition by Ro 20-1724 (3 microM) reduced alpha by 6- and 4-fold,
      respectively. A simultaneous application of milrinone and Ro 20-1724 produced a
      similar effect to IBMX, showing that PDE3 and PDE4 were the major PDEs accounting
      for cAMP compartmentation. Okadaic acid (3 microM), a non-selective phosphatase
      inhibitor, or H89 (1 microM), an inhibitor of cAMP-dependent protein kinase
      (PKA), had no effect on the distant response of ICa,L to ISO indicating that PDE
      activation by PKA played a minor role in cAMP compartmentation. Our results
      demonstrate that PDE activity determines the degree of cAMP compartmentation in
      frog ventricular cells upon beta2-adrenergic stimulation. PDE3 and PDE4 subtypes
      play a major role in this process, and contribute equally to ensure a functional
      coupling of beta2-adrenergic receptors with nearby Ca2+ channels via local
      elevations of cAMP.

PMID- 12815181
TI  - Novel modulatory mechanisms revealed by the sustained application of nicotine in
      the guinea-pig hippocampus in vitro.
AB  - The alpha 7 nicotinic acetylcholine receptor (nAChR) has been implicated widely
      in behavioural functions and dysfunctions related to the hippocampus, but the
      detailed mechanisms by which this receptor contributes to these behavioural
      processes have yet to be elucidated. In the present study, sustained application
      (5 min) of nicotine significantly lowered the threshold for synaptic plasticity,
      and thus a long-lasting potentiation was induced by a stimulus that would
      normally evoke only a short-term potentiation. This effect appeared to be
      mediated by alpha 7 nAChRs, as it was inhibited by the alpha 7 nAChR-specific
      antagonist alpha-bungarotoxin (100 nM), but not by mecamylamine (50 microM) or
      dihydro-beta-erythroidine (DH beta E; 1 microM) at concentrations known to be
      selective for non-alpha 7 nAChRs. Further pharmacological dissection revealed
      that the effect was also abolished by the NMDA receptor antagonist, D-(-)-2-amino
      5-phosphonopentanoic acid (D-AP5; 50 microM). This blockade, however, unmasked a
      slowly developing nicotine-induced potentiation of field excitatory postsynaptic
      potential that appeared to be dependent on both alpha 7 nAChR activation and non
      alpha 7 nAChR desensitisation. This secondary effect of nicotine was blocked by a
      combination of picrotoxin (50 microM) and saclofen (100 microM), and thus
      appeared to be mediated via GABAergic interneurons. The important implication of
      this study was that the sustained application of alpha 7 nAChR agonists could
      modulate the conditions for synaptic plasticity through multiple transduction
      pathways, and not simply the inactivation of alpha 7 nAChRs. These alpha 7-nAChR
      dependent mechanisms could reconcile the discrepancies between the previously
      reported behavioural versus electrophysiological effects of nicotine in the
      hippocampus. Effects of sustained alpha 7 nAChR stimulation Effects of sustained
      alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR stimulation Effects
      of sustained alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR
      stimulation

PMID- 12815182
TI  - Suppression of skeletal muscle lipoprotein lipase activity during physical
      inactivity: a molecular reason to maintain daily low-intensity activity.
AB  - We have examined the regulation of lipoprotein lipase (LPL) activity in skeletal
      muscle during physical inactivity in comparison to low-intensity contractile
      activity of ambulatory controls. From studies acutely preventing ambulatory
      activity of one or both the hindlimbs in rats, it was shown that approximately 90
      95 % of the heparin-releasable (HR) LPL activity normally present in rat muscle
      with ambulatory activity is lost, and thus dependent on local contractile
      activity. Similarly, approximately 95 % of the differences in LPL activity
      between muscles of different fibre types was dependent on ambulatory activity.
      The robustness of the finding that physical inactivity significantly decreases
      muscle LPL activity was evident from confirmatory studies with different models
      of inactivity, in many rats and mice, both sexes, three muscle types and during
      both acute and chronic (11 days) treatment. Inactivity caused a local reduction
      of plasma [3H]triglyceride uptake into muscle and a decrease in high density
      lipoprotein cholesterol concentration. LPL mRNA was not differentially expressed
      between ambulatory controls and either the acutely or chronically inactive
      groups. Instead, the process involved a rapid loss of the HR-LPL protein mass
      (the portion of LPL largely associated with the vascular endothelium) by an
      actinomycin D-sensitive signalling mechanism (i.e. transcriptionally dependent
      process). Significant decreases of intracellular LPL protein content lagged
      behind the loss of HR-LPL protein. Treadmill walking raised LPL activity
      approximately 8-fold (P < 0.01) within 4 h after inactivity. The striking
      sensitivity of muscle LPL to inactivity and low-intensity contractile activity
      may provide one piece of the puzzle for why inactivity is a risk factor for
      metabolic diseases and why even non-vigorous activity provides marked protection
      against disorders involving poor lipid metabolism.

PMID- 12815183
TI  - The detection of human finger movement is not facilitated by input from receptors
      in adjacent digits.
AB  - These experiments were designed to determine whether cutaneous input from a digit
      provides a general facilitation of the detection of movements applied to an
      adjacent digit. The ability to detect passive movements at the proximal
      interphalangeal joint of the right index finger was measured when cutaneous (and
      joint) input was removed (using local anaesthesia) from the tip of one or both
      digits adjacent to the test finger (16 subjects). The same parameter was also
      measured when input was artificially increased by stimulation of the adjacent
      digits at three intensities: below, above and at perceptual threshold (PT; 15
      subjects). Detection of flexion or extension movements was not altered by
      anaesthesia of one or both adjacent digits. Since it was possible that too few
      tonically active afferents in the hand had been blocked to reveal an effect, the
      median nerve was blocked, with movements applied to the little finger, causing no
      measurable impairment in acuity (three subjects). Simultaneous electrical
      stimulation of the tips of the adjacent digits at intensities above PT impaired
      movement detection, but had no effect when delivered at or below PT. To test
      whether the effect of detectable electrical stimuli was due to a specific
      interaction between the artificial input and the input evoked by moving the
      digit, or due to mental distraction, stimuli were delivered above PT to either
      the left or right little finger, or the test index finger during movement of the
      index finger. Electrical stimulation of the index finger significantly reduced
      detection by approximately 50%, but stimulation of the remote little fingers did
      not. Electrical stimulation is a non-natural stimulus, so a "natural" stimulus
      was applied by continuously stroking the tips of the adjacent digits with a brush
      (10 subjects). The natural stimulus also significantly reduced movement detection
      by approximately 50%. Together, these findings suggest that tonic inputs from
      digital nerve afferents adjacent to, or more remote from the passively moved
      finger do not facilitate movement detection. However, the reduced detection
      during stimulation of the adjacent digits shows that there is nevertheless some
      interaction between the various proprioceptive inputs from the digits.

PMID- 12815184
TI  - GABAB receptor transduction mechanisms, and cross-talk between protein kinases A
      and C, in GABAergic terminals synapsing onto neurons of the rat nucleus basalis
      of Meynert.
AB  - The transduction mechanisms underlying presynaptic GABAB receptor-mediated
      inhibition of transmitter release have been characterized for a variety of
      synapses in the central nervous system (CNS). These studies have suggested a
      range of transduction mechanisms, including a role for second messengers such as
      protein kinases A (PKA) and C (PKC). In the present study, we have examined the
      intracellular signalling pathways underlying baclofen-induced inhibition of GABA
      release from terminals synapsing onto rat basalis of Meynert neurons using patch
      clamp recordings. Baclofen, a selective GABAB receptor agonist, reversibly
      decreased both evoked and spontaneous, miniature, GABAergic inhibitory
      postsynaptic currents (eIPSCs and mIPSCs, respectively). Such baclofen actions
      were completely abolished by CGP55845A, a selective GABAB receptor antagonist,
      and by staurosporine, a non-selective PKA and PKC inhibitor. The mIPSC frequency
      was still decreased by baclofen even in the presence of 4 AP, a K+ channel
      blocker, and Cd2+, a voltage-dependent calcium channel blocker. Pharmacological
      activation or inhibition of PKC activity affected basal GABA release and mildly
      affected the response to baclofen. Inhibition of the cAMP/PKA cascade also
      affected basal GABA release and, in a subset of neurons, occluded the effects of
      baclofen, suggesting that the GABAB receptor-mediated inhibitory action on GABA
      release was mediated via decreases in PKA activity. In addition, PKA inhibition
      occluded the effects of PKC modulation on both basal GABA release and on the
      response to baclofen. Our results characterize the transduction pathway of
      baclofen at these nucleus basalis of Maynert (nBM) synapses and show, for the
      first time, some cross-talk between the cAMP/PKA and PKC pathways in mammalian
      presynaptic nerve terminals.

PMID- 12815185
TI  - Functional roles of cytoplasmic loops and pore lining transmembrane helices in
      the voltage-dependent inactivation of HVA calcium channels.
AB  - Voltage-dependent inactivation of calcium channels is a key mechanism for
      regulating intracellular calcium levels and neuronal excitability. In sodium and
      potassium channels, the molecular determinants that govern fast inactivation
      involve pore block by a cytoplasmic gating particle. As we discuss here, there is
      an increasing body of evidence that is consistent with a qualitatively similar
      inactivation mechanism in high-voltage-activated calcium channels. Work from a
      number of laboratories has implicated both cytoplasmic regions and the pore
      lining S6 transmembrane helices in the inactivation process. Together with our
      recent findings, this leads us to propose a model in which the intracellular
      domain I-II linker region acts as a 'hinged lid' that physically occludes the
      pore by docking to the cytoplasmic ends of the S6 segments. We further propose
      that the ancillary calcium channel Beta subunits differentially modulate
      inactivation kinetics by binding to and thereby regulating the mobility of the
      putative inactivation gate. Indeed, additional evidence suggests that the carboxy
      terminus, amino terminus and domain III-IV linker regions of the channel modulate
      inactivation rates through interactions with the I-II linker per se, or
      indirectly via the ancillary Beta subunits. Taken together, the fast voltage
      dependent inactivation of calcium channels appears reminiscent of that of sodium
      channels, but appears to show a more complex regulation through intramolecular
      interactions between the putative inactivation gate and other cytoplasmic
      regions.

PMID- 12815187
TI  - Force depression following muscle shortening of voluntarily activated and
      electrically stimulated human adductor pollicis.
AB  - The purpose of this study was to investigate steady-state force depression
      following active muscle shortening in human adductor pollicis during voluntary
      and electrically induced contractions. Subjects (n = 12; age 28 +/- 5 years; 7
      males and 5 females) performed isometric reference contractions and isometric
      shortening-isometric contractions, using maximal voluntary effort and near
      maximal electrical stimulation. Force depression was assessed by comparing the
      steady-state isometric forces produced following active muscle shortening with
      the purely isometric reference forces obtained at the corresponding muscle
      length. In order to test for effects of the shortening conditions on the steady
      state force depression, the amplitude and speed of shortening were changed
      systematically in a random order but balanced design. Thumb adduction force and
      carpometacarpal joint angle were continuously measured using a custom-designed
      dynamometer. During voluntary contractions, muscle activation was recorded using
      electromyography and the superimposed twitch technique. During electrically
      induced contractions, muscle stiffness was assessed using a quick-stretch method.
      Force depression during voluntary contractions, with a constant level of muscle
      activation, was similar to that obtained during electrically induced
      contractions. Force depression increased with increasing amplitudes of shortening
      (9.9 +/- 1.6%, 15.6 +/- 2.4% and 22.4 +/- 2.4% for 10, 20 and 30 deg of
      shortening, respectively) and decreased with increasing speeds of shortening
      (27.1 +/- 2.5%, 19.3 +/- 1.6% and 15.6 +/- 1.8% for 20, 60 and 300 deg s(-1) of
      shortening, respectively), regardless of the activation method. Muscle stiffness
      was significantly lower in the force-depressed state (5.9 +/- 0.2 N deg(-1))
      compared with that of the isometric reference contractions (7.2 +/- 0.3 N deg(
      1)), and decreased with increasing force depression (6.6 +/- 0.5, 6.0 +/- 0.5 and
      5.3 +/- 0.4 N deg(-1) for the 10, 20 and 30 deg of shortening test contractions,
      respectively). Force depression appeared to be fully established at the end of
      the shortening phase. The results of this study suggest that steady-state force
      depression for voluntary movements is similar to that observed using electrical
      stimulation. Furthermore, it appears that force depression is established at the
      end of the shortening phase and is associated with a reduction in muscle
      stiffness and thus, presumably, a decrease in the proportion of attached cross
      bridges.

PMID- 12815188
TI  - Signalling pathways involved in the sensitisation of mouse nociceptive neurones
      by nerve growth factor.
AB  - Nerve growth factor (NGF) causes a rapid sensitisation of nociceptive sensory
      neurones to painful thermal stimuli owing to an action on the heat and capsaicin
      receptor TRPV1 (formerly known as VR1). We have developed a new technique to
      study this rapid sensitisation of TRPV1 by monitoring the effects of NGF on the
      increase in intracellular calcium concentration ([Ca2+]i) following exposure to
      capsaicin. Brief applications of capsaicin caused a rise in [Ca2+]i, and NGF was
      found to enhance this rise in 37 % of capsaicin-responsive neurones within 2 min.
      Pathways responsible for transducing the sensitisation of TRPV1 by TrkA, the NGF
      receptor, were characterised by observing the effects of inhibitors of key
      members of NGF-activated second messenger signalling cascades. Specific
      inhibitors of the ras/MEK (mitogen-activated protein and extracellular signal
      regulated kinases) pathway and of phospholipase C did not abolish the NGF-induced
      sensitisation, but wortmannin, a specific inhibitor of phosphatidylinositol-3
      kinase (PI3K), totally abolished the effect of NGF. Pharmacological blockade of
      protein kinase C (PKC) or calcium-calmodulin-dependent protein kinase II (CaMK
      II) activation also prevented NGF-induced sensitisation, while blockade of
      protein kinase A (PKA) was without effect. These data indicate that the crucial
      early pathway activated by NGF involves PI3K, while PKC and CaMK II are also
      involved, probably at subsequent stages of the NGF-activated signalling pathway.

PMID- 12815191
TI  - Signaling receptome: a genomic and evolutionary perspective of plasma membrane
      receptors involved in signal transduction.
AB  - Intercellular communication in multicellular organisms requires the relay of
      extracellular signals by cell surface proteins to the interiors of cells. The
      availability of genome sequences from humans and several model organisms has
      facilitated the identification of several human plasma membrane receptor families
      and allowed the analysis of their phylogeny. This review provides a global
      categorization of most known signal transduction-associated receptors as enzymes,
      recruiters, and latent transcription factors. The evolution of known families of
      human plasma membrane signaling receptors was traced in current literature and
      validated by sequence relatedness. This global analysis reveals themes that recur
      during receptor evolution and allows the formulation of hypotheses for the
      origins of receptors. The human receptor families involved in signaling (with the
      exception of channels) are presented in the Human Plasma Membrane Receptome
      database.

PMID- 12815189
TI  - Voltage-gated K+ channels in rat small cerebral arteries: molecular identity of
      the functional channels.
AB  - Voltage-gated potassium (KV) channels represent an important dilator influence in
      the cerebral circulation, but the composition of these tetrameric ion channels
      remains unclear. The goals of the present study were to evaluate the contribution
      of KV1 family channels to the resting membrane potential and diameter of small
      rat cerebral arteries, and to identify the alpha-subunit composition of these
      channels using patch-clamp, molecular and immunological techniques. Initial
      studies indicated that 1 micromol l(-1) correolide (COR), a specific antagonist
      of KV1 channels, depolarized vascular smooth muscle cells (VSMCs) in pressurized
      (60 mmHg) cerebral arteries from -55 +/- 1 mV to -34 +/- 1 mV, and reduced the
      resting diameter from 152 +/- 15 microm to 103 +/- 20 microm. In patch clamped
      VSMCs from these arteries, COR-sensitive KV1 current accounted for 65 % of total
      outward KV current and was observed at physiological membrane potentials. RT-PCR
      identified mRNA encoding each of the six classical KV1 alpha-subunits, KV1.1-1.6,
      in rat cerebral arteries. However, only the KV1.2 and 1.5 proteins were detected
      by Western blot. The expression of these proteins in VSMCs was confirmed by
      immunocytochemistry and co-immunoprecipitation of KV1.2 and 1.5 from VSMC
      membranes suggested KV1.2/1.5 channel assembly. Subsequently, the pharmacological
      and voltage-sensitive properties of KV1 current in VSMCs were found to be
      consistent with a predominant expression of KV1.2/1.5 heterotetrameric channels.
      The findings of this study suggest that KV1.2/1.5 heterotetramers are
      preferentially expressed in rat cerebral VSMCs, and that these channels
      contribute to the resting membrane potential and diameter of rat small cerebral
      arteries.

PMID- 12815190
TI  - Attenuation of metabolic heat production and cold-escape/warm-seeking behaviour
      during a cold exposure following systemic salt loading in rats.
AB  - The reduction of body core temperature (Tcore) after salt loading has been
      reported. In this study, we tested the hypothesis that, during a cold exposure in
      rats, (1) salt loading would decrease metabolic rate (MR), reducing Tcore, but
      (2) Tcore would be maintained when cold-escape/warm-seeking behaviour is
      available. In the first experiment (n = 7), MR and Tcore were measured by
      indirect calorimetry and telemetry, respectively, during 26, 20 and 10 degrees C
      exposure for 1 h each, in that order. In the second experiment (n = 7), each rat
      was placed in an operant system during the same exposure protocol as in the first
      experiment, where it could trigger a 40 degrees C air reward for 30 s at 20 and
      10 degrees C by moving into specific areas (operant behaviour). In each
      experiment, rats repeated the same protocol twice with a subcutaneous injection
      (10 ml kg-1) of either isotonic saline (154 mM) or hypertonic saline (2500 mM).
      In the first experiment, MR in the isotonic-saline trial increased (P < 0.05) at
      20 and 10 degrees C compared with that at 26 degrees C by 21 +/- 5 and 48 +/- 6
      %, respectively (means +/- S.E.M.), with Tcore unchanged. However, values for MR
      and Tcore in the hypertonic-saline trial were lower (P < 0.05) than those in the
      isotonic-saline trial in any ambient temperature. In the second experiment, Tcore
      was also lower (P < 0.05) in the hypertonic-saline trial than in the isotonic
      saline trial. The counts of the operant behaviour in the hypertonic-saline trial
      remained unchanged in each exposure period, but those in the isotonic-saline
      trial increased (P < 0.05) at 10 degrees C. These results may suggest that salt
      loading attenuates both metabolic and behavioural thermoregulatory responses to
      the cold.

PMID- 12815192
TI  - Proteoglycan alterations and collagen reorganisation in the secondary avian
      cornea during development.
AB  - PURPOSE: It is thought that proteoglycan (PG) alterations, collagen matrix
      reorganisation and the onset of corneal transparency in the developing avian
      cornea might be related events. The current histochemical study was designed to
      establish the character and distribution of corneal PG filaments in relation to
      collagen organisation during tissue morphogenesis. METHODS: Corneas from days 13
      18 developing chicken embryos were treated with cuprolinic blue (CuB) to examine
      sulphated PGs by transmission electron microscopy and quantitative image
      analysis. RESULTS: On developmental day 13, corneas contained poorly defined
      lamellae and a large number of both small and large CuB-stained PG filaments,
      randomly distributed and often in collagen-free regions. By day 14 and after, the
      large CuB-stained PG filaments were much less abundant. At this time, too,
      collagen fibrils displayed an axial alignment and an occasional periodic
      arrangement of small CuB-stained PG filaments along their axes. By developmental
      day 15, lamellae were well formed and continued to increase in number and size
      thereafter. Between developmental days 16 and 17, there was a significant
      increase (p < 0.001) in the number of small, collagen-associated PG filaments.
      This increase persisted into day 18. CONCLUSIONS: The size, number and
      distribution of sulphated, CuB-stained PG filaments in the developing avian
      cornea change over time. This is particularly true between developmental days 13
      and 14 and between days 16 and 17, concurrent with previously documented
      structural changes.

PMID- 12815193
TI  - Effects of cataractogenesis on the CDP-choline pathway: changes in ATP
      concentration and phosphocholine synthesis during and after exposure of rat
      lenses to sugars in vitro and in vivo.
AB  - We measured choline influx and phosphorylation, ATP concentration ([ATP]),
      choline kinase activity and lens swelling during formation and partial reversal
      of sugar cataracts in rat lenses incubated with xylose or galactose and in lenses
      of galactosemic rats. [ATP] and phosphocholine (P-Cho) synthesis decreased about
      60 and 40% after 4 h in normal rat lenses incubated up to 24 h in medium
      containing 30 mM xylose and partially recovered when the lenses were then removed
      from the xylose. Incubation with the somewhat less cataractogenic sugar galactose
      decreased P-Cho synthesis but had little effect on [ATP]. P-Cho synthesis
      decreased rapidly in the lenses of rats fed a 50% galactose diet, but began
      recovery by the third day on this diet. [ATP] decreased for at least 10 days
      during the galactose diet and did not recover, even with resumption of the
      control diet (50% starch) after 4 or 7 days. The results of in vitro and in vivo
      sugar cataractogenesis differed from each other in several respects, including
      effects on choline influx and the degree to which the changes were reversible.
      The in vitro and in vivo sugar cataracts, however, could both produce swelling
      and opacification of the lens and decreased P-Cho synthesis and [ATP]. Neither
      model caused a substantial change in the choline kinase activity (as measured in
      cell-free assays). The data did not generally support the hypothesis that
      decreased [ATP] causes decreased P-Cho synthesis.

PMID- 12815194
TI  - Vitrectomy for diabetic macular edema: effect of glycemic control (HbA(1c)),
      renal function (creatinine) and other local factors.
AB  - AIMS: To determine the effect of preoperative factors on the foveal thickness
      following vitrectomy for diabetic macular edema. METHODS: Fifty-eight eyes of 47
      patients underwent vitrectomy for diabetic macular edema. In all eyes, no clear,
      visible vitreomacular traction was present. Twelve eyes were pseudophakic before
      vitrectomy, and 31 eyes underwent concurrent phacoemulsification and intraocular
      lens (IOL) implantation. Multiple logistic regression analysis was used to assess
      the independent effect of age, history of photocoagulation, diabetic retinopathy
      status, preoperative posterior vitreous detachment, HbA(1c) and serum creatinine
      levels within 2 weeks before surgery, lens status after surgery and follow-up
      period on the foveal thickness determined by optical coherence tomography.
      RESULTS: The median preoperative visual acuity was 20/100 (range from 20/500 to
      20/20), and the median postoperative visual acuity was 20/70 (range from 20/500
      to 20/13). The preoperative visual acuity (logarithm of minimal angle of
      resolution; logMAR) was 0.73 +/- 0.36 (mean +/- SD; 20/107 Snellen acuity), and
      the mean postoperative logMAR visual acuity was 0.60 +/- 0.39 (20/80), which was
      significantly better than the mean preoperative value (Wilcoxon signed rank test,
      p = 0.011). The mean +/- SD of preoperative foveal thickness was 475.9 +/- 172.5
      micrometer, and the mean postoperative foveal thickness was 277.3 +/- 171.9
      micrometer. The mean postoperative foveal thickness was significantly thinner
      than the preoperative thickness (Student's paired t test, p < 0.0001). Multiple
      logistic regression analysis showed that a preoperative low HbA(1c) and
      postoperative pseudophakia were independently associated with the decrease in
      foveal thickness (p = 0.01, p = 0.04, respectively). CONCLUSIONS: The greater
      reduction in foveal thickness in eyes with an IOL probably resulted from a
      relatively larger amount of vitreous being removed during the vitrectomy. Because
      the decrease in foveal thickness may be related to the preoperative glycemic
      control and the amount of vitreous, these factors should be considered in the
      planning for vitrectomy.

PMID- 12815195
TI  - Expression of tissue inhibitor of metalloproteinase-4 in normal human corneal
      cells and experimental corneal neovascularization.
AB  - PURPOSE: To study the expression of TIMP-4 in cultured corneal cells and in
      corneal neovascularization. METHODS: Human limbo-corneal epithelial cells,
      fibroblasts, and endothelial cells were cultured in serum-free, PMA- or basic
      fibroblast growth factor (bFGF)-treated condition. Neovascularization in rat
      cornea was induced by suturing. The expression of TIMP-4 was examined by
      immunohistochemistry, Western blot and RT-PCR. RESULTS: TIMP-4 was constitutively
      expressed in cultured human corneal cells. The expression was only mildly
      enhanced after mitogen treatment. TIMP-4 immunoreactivity was predominantly
      expressed in normal rat corneal epithelium, and also in ingrowing blood vessels
      following suturing, which persisted up to day 28. Increased staining in corneal
      epithelium and blood vessels were also noted in vascularized human corneas.
      CONCLUSIONS: TIMP-4 is expressed in the cornea, which may play a role in
      modulating extracellular matrix remodeling associated with corneal wound healing
      and angiogenesis.

PMID- 12815196
TI  - UV-Absorbing compounds in the aqueous humor from aquatic mammals and various non
      mammalian vertebrates.
AB  - OBJECTIVE: To evaluate the absorbance of ultraviolet radiation (UVR) in the
      aqueous humor of various animal species in relation to the ambient radiation of
      their respective habitats, and to identify substances responsible for this
      absorbance. Representatives of all five classes (fish, amphibian, reptile, bird,
      and mammal) have been tested. METHODS: Absorbance was recorded using a
      spectrophotometer. The ascorbic and uric acid concentrations were determined by
      HPLC, and the amino acid profiles with an automatic analyzer. Screening for
      potential UV-absorbing substances was performed by HPLC and a total of 12 species
      were examined, 7 of them birds. RESULTS: UV-absorbing substances in the aqueous
      humor were proteins, tryptophan, tyrosine and ascorbic and uric acid. In
      addition, an unknown UV-absorbing component present in bird aqueous humor caused
      a high, red-shifted UV-absorbance spectrum, particularly in tentatively heavily
      exposed species such as goose when migrating at 10,000 m altitude. By comparison,
      the UV absorbance above the 288-nm wavelength was low in the aqueous humor of
      fish, frogs, aquatic mammals and two ground-living birds. The crocodile, whose
      aqueous humor contained significant amounts of both ascorbic and uric acid,
      revealed a concentration mechanism for ascorbic acid. CONCLUSIONS: The UV
      absorbance of aqueous humor varies considerably from one species to the next, and
      independent of class. It is noteworthy that the species being at highest risk for
      high-dose UV exposure, the migrating goose, showed the most red-shifted spectrum.

PMID- 12815197
TI  - Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in
      fibrovascular membrane from patients with retinopathy of prematurity.
AB  - PURPOSE: The tyrosine kinase receptor Tie2 and its ligands, the angiopoietins
      (Angs), play important roles in vascular integrity and neovascularization,
      modulating vascular endothelial growth factor (VEGF) activity. To elucidate the
      potential role of Angs and the Tie2 system in retinopathy of prematurity (ROP),
      we have investigated the expression of Angs, Tie2 and VEGF within
      fibroproliferative membranes in ROP. METHODS: Fibroproliferative membranes were
      obtained from 38 cases with stage 5 ROP at the time of vitrectomy. Membranes were
      fixed in formalin and embedded in paraffin. Each specimen was serially sectioned
      for immunohistochemistry. Polyclonal antibodies specific for Ang1, Ang2, Tie2 and
      VEGF were used for immunostaining. Immunoreactivity for von Willebrand factor
      (factor VIII) was also assessed to confirm the identity of vascular endothelial
      cells. RESULTS: Positive staining for Tie2 was observed in 23 of 38 specimens
      (60.5%). Tie2 was localized in vascularized regions of fibrovascular membranes
      and was co- expressed with VEGF and factor VIII. Ang2 stained positively in 18 of
      38 (47.3%) serial sections where Tie2 was present, and was also co-expressed with
      VEGF and factor VIII. Ang1 was not generally observed in these specimens (3/38).
      CONCLUSIONS: VEGF and Ang2-Tie2 interactions may play an important role in the
      pathogenesis of ROP.

PMID- 12815198
TI  - Phylogenetic assessment of the mitochondrial DNA displacement loop haplotype in
      Japanese patients with Leber's hereditary optic neuropathy harboring the
      mitochondrial DNA G11778A mutation.
AB  - To investigate the anthropological background and the association of
      mitochondrial DNA (mtDNA) haplotype with the disease phenotype, the nucleotide
      sequence in the hypervariable segment of the displacement loop (D-loop) region of
      mtDNA was determined in Japanese patients with Leber's hereditary optic
      neuropathy (LHON) harboring the G11778A mutation. Genetic polymorphism of mtDNA
      was examined in 36 unrelated Japanese LHON patients who presented with bilateral
      optic nerve disease and had the mtDNA G11778A mutation. DNA was extracted from
      the peripheral blood after having obtained informed consent. The nucleotide
      sequence of the D-loop region (np 16,002-16,490) was directly determined. The
      intergenic deletion of the COII/tRNA(Lys) gene of mtDNA was also examined. From
      the data set of nucleotide alignments, the phylogeny of the mtDNA sequence and
      phenotypic diversity within the examined population were evaluated. One-base
      polymorphism was present at 37 different sites. The estimated value of nucleotide
      diversity was 0.69%. D-loop sequences were classified into 13 monophyletic
      clusters (CA to CM). There was not any definite ancestral haplotype of the D-loop
      sequence in the examined LHON population. Thus, the mutational event of G11778A
      appears to be independent of the evolutionary course in the D-loop haplotype.
      Patients with a CD plus CH cluster had a significantly older age at onset (p =
      0.006), and had a family history being significantly lower as compared with
      patients with other clusters (p = 0.05). The mtDNA D-loop haplotype characterized
      by the presence of T16362C or C16290T, lacking G16129A and G16390A, may be a risk
      for older age at onset and other unusual clinical features in Japanese LHON
      patients with the G11778A mutation.

PMID- 12815199
TI  - Proliferative vitreoretinopathy: cytologic findings in vitreous samples.
AB  - PURPOSE: To compare the cellularity of vitreous samples obtained from patients
      with rhegmatogenous retinal detachment complicated by proliferative
      vitreoretinopathy (PVR) and from patients with uncomplicated rhegmatogenous
      retinal detachment (RD) to detect possible variations in cellularity over time.
      METHODS: One hundred and twenty-five vitreous specimens collected from patients
      with RD (n = 41) and PVR (n = 84) were processed through direct paraffin
      embedding and cytospin. Different cell types were identified by light-microscopy
      (hematoxylin-eosin and Papanicolaou stain) according to their morphologic
      features, and a scale of cellular density was established for each cell type.
      Student's t test was used to analyze differences in the cellularity of RD versus
      PVR. A quadratic model was used to identify variations in the density of each
      cellular type in the PVR group, based on its evolution time. RESULTS: During the
      first months after surgery, more macrophages and fibroblast-like cells were
      observed in the PVR group, but at other times no differences were found.
      CONCLUSIONS: There are some differences in vitreous cellularity in PVR specimens
      when compared with RD. Especially relevant could be the large number of
      macrophages in earlier stages and their constant presence over time in PVR
      samples. The cytology of vitreous samples may shed light on the chronology of PVR
      cell pathobiology.

PMID- 12815203
TI  - The art of fusion: from penams and cephems to penems.
AB  - This synopsis of published literature summarises the key chemical and
      bacteriological characteristics of penicillins, i.e. penams, cephalosporins, i.e.
      cephems, and their hybrid structure, i.e. the penems. Consequently, the
      antibacterial spectrum of a typical penem, e.g. faropenem, encompasses gram
      positive as well as gram-negative species. Dependent from the substituents at
      position 1 of the five-membered saturated ring fused to the beta-lactam ring oxa
      , carba-, or thiopenems can be differentiated. A major determinant of their
      antibacterial activity and CNS-excitatory potential, however, is the C-2 side
      chain. The excitatory potential correlates with the basicity of the C-2 side
      chain as does their antibacterial activity against gram-negative species and non
      fermenters like P. aeruginosa. Lipophilicity is a determinant for good in vitro
      activity against gram-positive bacteria. Several investigational penems exhibit
      interesting antibacterial spectra, encompassing methicillin resistant
      staphylococci, enterococci and even P. aeruginosa due to their improved binding
      affinity to both wild-type and modified low-affinity penicillin binding proteins.
      The development of these agents may offer therapeutic alternatives for the
      management of infections.

PMID- 12815204
TI  - Effect of Varidase (streptodornase) on biofilm formed by Pseudomonas aeruginosa.
AB  - The biofilm of Pseudomonas aeruginosa could be removed by Varidase
      (streptodornase) that was used as defibrinating drug. After cultivating the
      biofilm on a silicone chip in a modified alginate-producing medium in vitro, it
      was treated with Varidase or DNase I. In both treatments, the biofilm was removed
      depending on the concentration of the reagents. Varidase was apparently effective
      under the condition that the biofilm was exposed to more than 625 U/ml (a quarter
      of the concentration of the medical use) for 3 h, twice, at 37 degrees C. The
      result of this experiment indicates that (a) the DNases, DNase I and Varidase,
      were effective in destroying the biofilm of P. aeruginosa in vitro, and (b) in a
      clinical field, Varidase could be useful for P. aeruginosa focal infection, such
      as urinary tract infection, by removing the biofilm.

PMID- 12815205
TI  - Comparative effects of cidofovir and cyclic HPMPC on lethal cowpox and vaccinia
      virus respiratory infections in mice.
AB  - BACKGROUND: Cidofovir is approved for the treatment of cytomegalovirus retinitis
      in humans. Although highly effective, the drug can cause renal toxicity in
      patients. There is much interest in cidofovir as a potential treatment for
      smallpox, monkeypox and other orthopoxvirus infections. A cyclic phosphonate form
      of cidofovir, 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5
      yl)methyl]cytosine (cyclic HPMPC), was reported to be less nephrotoxic than
      cidofovir in animals. Thus, it was deemed important to directly compare the
      activities of cidofovir and cyclic HPMPC against poxvirus infections in mouse
      models. METHODS: The compounds were evaluated by intraperitoneal and intranasal
      infection routes using multiple doses of each agent, with single doses of
      compound given 24 h after virus challenge. RESULTS: By intraperitoneal route,
      cidofovir protected mice from mortality at 40, 80 and 160 mg/kg, whereas cyclic
      HPMPC was similarly protective only at 160 mg/kg. By intranasal route, cidofovir
      was active down to 5 mg/kg, compared to cyclic HPMPC efficacy at 20 and 40 mg/kg.
      Intraperitoneal doses of 40, 80 and 160 mg/kg cidofovir significantly reduced
      mortality from vaccinia virus infections, compared to doses of 80 and 160 mg/kg
      cyclic HPMPC. Intranasal treatment with cidofovir at 5-40 mg/kg was comparably
      effective to cyclic HPMPC doses of 20 and 40 mg/kg in vaccinia virus infections.
      Active doses significantly reduced lung virus titers and lung consolidation.
      Overall, the potency of cyclic HPMPC was about 4 times less than that of
      cidofovir. CONCLUSIONS: Although cyclic HPMPC is reported to exhibit reduced
      nephrotoxicity in vivo, it is also less potent than cidofovir against
      orthopoxvirus infections. For this reason, cyclic HPMPC may not offer any
      advantage over cidofovir in treating these infections in humans.

PMID- 12815206
TI  - Genotoxic action of cycloplatam, a new platinum antitumor drug, on mammalian
      cells in vivo and in vitro.
AB  - Cycloplatam (CP), a new antitumor platinum compound of the second generation, was
      first synthesized in Russia. This drug shows less toxicity in vivo than the
      widely used cisplatin and carboplatin and a higher antitumor activity than
      carboplatin. CP is not nephrotoxic with respect to the platinum-based antitumor
      agents. CP is actually studied in clinical phase II trials in Russia and Armenia.
      Promising results were obtained in patients with lung, ovary, and prostate
      cancers. The aim of this work was to study the micronuclei (MN) inducing effect
      of CP in vivo in murine bone marrow cells and in human lymphocytes in vitro. The
      mutagenic activity of CP in bone marrow of mice was significantly lower than that
      of cisplatin at equitoxic doses. In human lymphocytes CP induced a dose-dependent
      increase of MN, beginning at a very low dose (0.1 micro M). Our results showed
      that CP is much less toxic and MN inducing in vivo in murine bone marrow than
      cisplatin. In vitro data evidenced that CP is more toxic and genotoxic to human
      cells than cisplatin. The evidence of a MN-induced activity of an antitumor drug
      suggests a potential risk for long-time survivors.

PMID- 12815207
TI  - Long-term survival in acute lymphoblastic leukaemia in adults treated according
      to the LALA 87 protocol.
AB  - BACKGROUND: Between January 1989 and July 1995, a prospective study of the
      therapeutic efficacy of the LALA 87 protocol in adult acute lymphoblastic
      leukaemia (ALL) has been conducted. METHODS: A total of hundred and twelve
      patients with ALL have been analysed. The median age of the patients was 40 years
      (range: 15-65), the gender ratio (M/F) was 66/46, and the morphologic FAB (French
      American-British) profile was L1 in 30 (26.9%) patients, L2 in 71 (63.3%) and L3
      morphology in 11 (9.8%) of the patients. The LALA 87 protocol includes five
      phases: induction, consolidation, reinforcement, maintenance and central nervous
      system (CNS) prophylaxis with intrathecal methotrexate and irradiation. The
      induction phase comprised daunorubicin 50 mg/m(2) (days 1-3), cyclophosphamide
      600 mg/m(2) (days 1 and 8), vincristine 1.5 mg/m(2) (on days 1, 8, 15 and 22) and
      daily oral prednisone on days 1-21. Maintenance therapy was given for 2 years and
      consisted of different drugs as reinforcement, daily 6-mercaptopurine and weekly
      methotrexate. RESULTS: Complete remission (CR) was achieved in 81 (72.3%) of the
      patients. The causes of induction failure were partial response in 10 (8.9%), and
      hypoplastic death in 12 patients (10.7%), and 9 were non-responders (8.0%). Of
      the 81 patients who achieved CR, 62 relapsed (76%). Among the relapsed patients,
      9 developed CNS disease in spite of CNS prophylaxis during induction
      chemotherapy. Median follow-up for the living patients was 110 months. Median
      disease-free survival (DFS) was 16 months; 19 patients are still in remission
      with an estimated 10-year DFS (24%). Adverse prognostic factors were >50 years of
      age, immunologic subtype and cytogenetic profile. CONCLUSION: The results support
      the strategy of applying more effort and other treatment modalities in the
      therapy of ALL.

PMID- 12815208
TI  - Antitumor efficacy of reticulol from Streptoverticillium against the lung
      metastasis model B16F10 melanoma. Lung metastasis inhibition by growth inhibition
      of melanoma.
AB  - Reticulol was isolated from the culture broth of the strain Streptoverticillium
      sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity
      against A427, a human lung tumor cell line, and B16F10, a mouse melanoma cell
      line. In the trypan blue staining assay for B16F10 cells, the cell viability by
      reticulol treatment was significantly decreased in a dose-dependent manner. The
      in vivo assay for the lung metastasis-blocking effect showed that reticulol
      injected intravenously suppressed the increase in colonies on the lung in a dose
      dependent manner. In addition, the survival rate of tumor-implanted mice treated
      with reticulol was closely associated with its antitumoral efficacy. Reticulol
      administered via the peritoneum of mice showed less metastasis inhibition than
      that injected intravenously. To demonstrate the mechanism for inhibition of
      metastasis, the inhibitory effect of reticulol for matrix metalloproteinase-2 or 
      9 involved in melanoma metastasis was investigated; however, they were not
      observed on zymogram gel. In addition, the antitumor efficacy of reticulol was
      not associated with cell cycle arrest or apoptosis. Therefore, it was inferred
      that reticulol known as a phosphodiesterase inhibitor directly inhibited the
      growth of B16F10 melanoma, showing necrotic response. These results suggest that
      reticulol protects its lung metastasis via the bloodstream by inhibiting the
      growth of B16F10 melanoma at the cellular level.

PMID- 12815209
TI  - A phase II trial of gemcitabine in the treatment of advanced bile duct and
      periampullary carcinomas.
AB  - BACKGROUND: Gemcitabine is a novel nucleoside analogue with clinical anticancer
      activity in several malignancies. From September 1998 to April 2000, we treated
      patients with advanced bile duct and periampullary carcinomas with gemcitabine
      alone. METHODS: Gemcitabine 1,000 mg/m(2)/day was administered in 200 ml of
      normal saline as a 30-min intravenous infusion on day 1 weekly for 3 weeks,
      followed by a 1-week rest. RESULTS: A total of 24 consecutive patients (15 men, 9
      women), with a median age of 59.5 years (range 40-72 years), were enrolled. All
      patients were evaluable for response: 1 patient achieved complete remission (CR);
      2 patients had partial remission (PR); 8 patients remained stable (SD), and 13
      patients had progressive disease (PD). The overall response rate (CR + PR) was
      12.5% with a 95% confidence interval (CI) of 2.7-32.4%. The median progression
      free survival (PFS) was 2.5 months (95% CI 1.6-5.5 months), and the median
      overall survival (OS) was 7.2 months (95% CI 3.8-8.9 months). Patients with
      disease control (CR + PR + SD) had better PFS and OS than those with PD. There
      were no treatment-related deaths. Few patients encountered grade 3/4 toxicity.
      CONCLUSION: Chemotherapy with gemcitabine demonstrated notable activity and was
      associated with a well-tolerable toxicity profile in patients with advanced
      biliary tract malignancies.

PMID- 12815210
TI  - Lepocreadiidae (Digenea) from the batfish of the genus Platax Cuvier (Teleostei:
      Ephippidae) from the southern Great Barrier Reef, Queensland, Australia.
AB  - The following species are described from Platax spp.: Neomultitestis
      aspidogastriformis n. sp., from P. teira, off Heron Island, Queensland, which can
      be distinguished from its congeners by the transversely elongate ventral sucker
      divided into three loculi and probably by testis number; Multitestis
      magnacetabulum Mamaev, 1970, from P. teira, off Heron Island, Queensland;
      Diploproctodaeum rutellum (Mamaev, 1970), from P. teira, off Heron Island,
      Queensland; Diploproctodaeum tsubameuo n. sp., from P. batavianus, from the Swain
      Reefs, off Queensland, which differs from its congeners in its overlapping,
      posteriorly attenuated testes and 38-55 ovarian lobes; and Diplocreadium sp.,
      from P. batavianus, from the Swain Reefs, off Queensland.

PMID- 12815211
TI  - A survey of coccidian infections of freshwater fishes of Peninsular Malaysia,
      with descriptions of three species of Goussia Labbe, 1896 (Apicomplexa:
      Eimeriidae).
AB  - Ninety-five specimens of 14 freshwater fish species from small streams in the
      Kuala Terengganu district and the Lake Kenyir Reservoir, Malaysia, were surveyed
      for coccidian infections. Six fish species proved to be infected with
      apicomplexans belonging to the genus Goussia. In all of these fishes Goussia
      species were found in unsporulated and semisporulated stages. Oocysts of four
      species inhabiting the intestinal epithelium became sporulated in tap-water
      within 24 hours. In two fish species sporulation failed and only unsporulated
      oocysts were recorded in the intestine. Three of the intestinal species finishing
      sporulation proved to be new to science and were described as Goussia malayensis
      n. sp., G. bettae n. sp. and G. pogonognathi n. sp. from Apocheilus panchax,
      Betta splendens and Hemirhamphodon pogonognatus, respectively. The fourth
      species, found in Trichogaster pectoralis, was identified as G. trichogasteri
      Szekely & Molnar, 1992, a species known from aquarium-cultured T. trichopterus.

PMID- 12815212
TI  - Cysticercoids of five species of Raillietina Fuhrmann, 1920 (Cestoda:
      Davaineidae) in ants, Pheidole sp., from emu farms in Australia.
AB  - Cysticercoids of five species of Raillietina, R. australis (Krabbe, 1869)
      Fuhrmann, 1924, R. beveridgei O'Callaghan, Davies & Andrews, 2000, R. chiltoni
      O'Callaghan, Davies & Andrews, 2000, R. dromaius O'Callaghan, Davies & Andrews,
      2000 and R. mitchelli O'Callaghan, Davies & Andrews, 2000, parasitic in the emu
      Dromaius novaehollandiae Latham, are described. Each species was identified on
      the basis of the number and size of the rostellar hooks, which correspond to
      those of adult worms. Cysticercoids were recovered from the haemocoele of the
      gaster of ants belonging to the genus Pheidole (Hymenoptera: Formicidae) in
      Australia. There was a trend towards an inverse relationship between the size of
      the cysticercoids and the parasite burden in the intermediate host.

PMID- 12815213
TI  - Morphological variability of Dicrogaster contracta Looss, 1902 (Digenea:
      Haploporidae) and its proposed synonymy with D. perpusilla Looss, 1902.
AB  - Dicrogaster contracta and D. perpusilla were originally described about 100 years
      ago from the thicklip grey mullet Chelon labrosus. Subsequent studies have
      reported D. contracta in several mullet species in the Mediterranean, Azov and
      Caspian Seas, but D. perpusilla has never been reported again. Since previous
      evidence suggests that the distinguishing features between these two species are
      uncertain, this study provides new and additional data on the variability of
      morphometric and meristic characters of D. contracta in order to assess their
      usefulness for differentiating this species from D. perpusilla. Body
      measurements, egg counts and shape statistics of three sets of specimens of D.
      contracta from different hosts and localities were compared with similar
      information from previous studies, including the original descriptions of D.
      contracta and D. perpusilla. The results showed consistent differences between
      the three sets in metric measurements, egg counts and shape statistics. In
      addition, the values of morphometric and meristic characters of D. perpusilla
      fell within the range of variation recorded for D. contracta. Neither
      conventional body measurements, eggs counts, nor shape statistics seemed useful
      to distinguish D. contracta from D. perpusilla, suggesting that they represent
      the same species. Accordingly, the valid designation of the species should be D.
      perpusilla because it is the type-species of the genus. This study proposes a
      neotype for D. perpusilla, since no type-specimens seem to be available, and
      provides additional morphologic data that might be useful for diagnosis of the
      genus Dicrogaster.

PMID- 12815214
TI  - Suttonema delta n. g., n. sp. (Nematoda: Trichostrongylina: Heligmosomoidea) from
      Oxymycterus rufus (Rodentia: Sigmodontinae) in Argentina.
AB  - A new nippostrongyline, Suttonema delta n. g., n. sp., is described from the
      intestine of Oxymycterus rufus (Rodentia: Sigmodontinae) from Argentina, in a
      host from which trichostrongylid nematodes were hitherto unknown. The new genus
      is very similar to Stilestrongylus Freitas, Lent & Almeida, 1937 and Malvinema
      Digiani, Sutton & Durette-Desset, 2003, both parasites of Neotropical
      sigmodontines, in the features of the caudal bursa (with a pattern of type 1-4,
      asymmetrical with hypertophied right lobe) and the presence of cephalic
      structures resembling cuticular cordons. The larval synlophe is also identical to
      that of Stilestrongylus freitasi Durette-Desset, 1968. The new genus is
      differentiated by an adult synlophe with few ridges (9-12 at mid-body) of two
      different types: small, rounded ridges without cuticular support on the dorsal
      side, and pointed ridges of unequal size on the ventral side and in lateral
      fields. It is also characterised by the presence of comaretes on the left ventral
      and ventral fields of the synlophe.

PMID- 12815216
TI  - Studies on the morphology and taxonomy of three new myxosporeans of the genus
      Sinuolinea Davis, 1917 (Myxosporea: Sinuolineidae) infecting the urinary bladder
      of some marine fishes from the Shandong coast, China.
AB  - The morphology and taxonomy of three new species of myxosporeans (Myxosporea:
      Sinuolineidae), Sinuolinea shandongensis n. sp., S. argyrosomi n. sp. and S.
      platycephali n. sp., parasitising marine fishes collected from the Yellow Sea off
      the coast of southeast Shandong, China, were investigated. These species,
      including spores and plasmodia, were found in the urinary bladder of their hosts.
      The diagnostic features of the new species are as follows. S. shandongensis n.
      sp. from Nibea albiflora: monosporous and disporous plasmodia, 29-37 x 29-27
      microm; spore inversely pyramidal or spherical, with smooth surface and fine,
      highly sinuous sutural line, 16.4+/-2.4 (15-20) x 16.1+/-1.1 (15-18) microm; two
      spherical polar capsules located anteriorly and conspicuously separated from each
      other, 4.8+/-0.3 (4.5-5.5) microm in diameter; length of polar filament 59-61
      microm; coelozoic. S. argyrosomi n. sp. from Argyrosomus argentatus: monosporous
      plasmodium, (33-42) x (24-25) microm; spore subspherical to spherical, with
      smooth surface and highly sinuous sutural line, 18.1+/-1.0 (17-20) x 19.8+/-1.3
      (18-22) microm; two spherical polar capsules located anteriorly and conspicuously
      separated from each other, 4.4+/-0.2 (4-5) microm in diameter; length of polar
      filament 47-50 microm; coelozoic. S. platycephali n. sp. from Platycephalus
      indicus: monosporous, disporous and polyporous plasmodia, 25-42 x 17-31 microm;
      spore spherical with smooth surface and highly sinuous sutural line, 14.5+/-0.5
      (14-15) microm in diameter; two spherical polar capsules located anteriorly and
      conspicuously separated from each other, 4.3+/-0.2 (4-4.5) microm in diameter;
      coelozoic.

PMID- 12815215
TI  - The crossroads of molecular, typological and biological species concepts: two new
      species of Gyrodactylus Nordmann, 1832 (Monogenea: Gyrodactylidae).
AB  - Nucleotide sequences of nuclear ribosomal DNA internal transcribed spacers (ITS)
      were used to confirm morphological identification of Gyrodactylus species in
      Fennoscandia. Three pairs of morphologically similar or cryptic species are
      compared in this study. G. branchicus Malmberg, 1964 and G. rarus Wegener, 1910,
      hosted by the sticklebacks Gasterosteus aculeatus L. and Pungitius pungitius
      (L.), respectively, displayed a genetic divergence of 0.9-1.3% along 774
      nucleotides of ITS (Jukes & Cantor distance). G. branchicus isolates from the
      Baltic, White Sea and Scottish North Sea were invariable, but a Belgian North Sea
      population with a 0.4% divergence in ITS sequence has been collected. The species
      status of G. branchicus and G. rarus is supported by host-specificity in
      sympatric habitats and consistent morphological difference in the marginal hook
      sickles. Among Gyrodactylus on burbot Lota lota (L.) specimens were collected
      with their 792 bp long ITS sequences differing by 8.5%. This has led to the
      splitting of G. lotae Gusev, 1953 into two species, G. lotae and G. alexgusevi n.
      sp. The species are morphologically separable, and a similar range of variation
      was found in both the anchors and the marginal hooks in other collections and in
      the original description. Among G. macronychus-like parasites of minnow Phoxinus
      phoxinus (L.), divergent ITS sequences indicate two cryptic species. By
      comparison with the type-specimens, one was identified as G. macronychus
      Malmberg, 1957; the other is here designated as G. jussii n. sp., differing by
      21.8% in 950-973 bp long ITS. The consequences of these findings for the species
      concept and species identification of Gyrodactylus are discussed.

PMID- 12815217
TI  - Dactylomyza gibsoni n. g., n. sp. (Digenea: Opecoelidae) from Schuettea woodwardi
      (Waite) (Monodactylidae) from off Western Australia.
AB  - An opecoelid digenean, Dactylomyza gibsoni n. g., n. sp. is described and figured
      from Schuettea woodwardi (Waite), a monodactylid from off the coast of Western
      Australia. The new genus conforms to the concept of the opecoelid subfamily
      Opecoelinae. The resemblance of the new genus to three other opecoelid genera,
      Pseudopecoeloides Yamaguti, 1940, Opecoeloides Odhner, 1928 and Poracanthium
      Dollfus, 1948, is discussed. Dactylomyza n. g. is distinguished from these
      morphologically similar worms on the basis of its median genital pore, ventral
      sucker appendages, uroproct and the absence of an accessory sucker.
      Pseudopecoeloides equesi Manter, 1947 is transferred to the new genus as
      Dactylomyza equesi (Manter, 1947) n. comb.

PMID- 12815218
TI  - Bartoliella pritchardae n. g., n. sp. (Digenea: Opecoelidae) in Epinephelides
      armatus (Serranidae) from temperate marine waters of Western Australia.
AB  - An opecoelid, Bartoliella pritchardae n. g., n. sp., is described from the
      intestine of Epinephelides armatus from Western Australia. The new genus has been
      assigned to the subfamily Opecoelininae Gibson & Bray, 1984, bringing the number
      of genera in the subfamily to two. Although the new genus is similar to
      Opecoelina Manter, 1934 morphologically, the pedunculate ventral sucker and
      complete absence of a cirrus-sac necessitate the erection of a new genus. A
      formal re-definition of the subfamily is given, based on the diagnoses of the
      genera Opecoelina and Bartoliella n. g.

PMID- 12815219
TI  - Monodelphoxyuris dollmeiri n. g., n. sp. (Nematoda: Oxyurida) from Monodelphis
      emiliae in Peru.
AB  - Monodelphoxyuris dollmeiri n. g., n. sp. is described from the caecum of
      Monodelphis emiliae (Thomas) (Marsupiala: Monodelphidae) collected in the eastern
      region of the Andes of Peru. M. dollmeiri n. sp. differs from the closest pinworm
      described from marsupials in the Neotropics (Didelphoxyuris thylamisis Gardner &
      Hugot, 1995) in having operculate eggs and males that possess a tip prolonged of
      tail and a different kind of area rugosa. Several other species of pinworms have
      been described from marsupials in Australia, but all are characterised by
      possessing of a buccal capsule that is strongly cuticularised with interradial
      lamellae. These structures are lacking both in M. dollmeiri and D. thylamisis.
      Monodelphoxyuris n. g. is characterised by a mouth opening into a depression and
      lateral alae composed of two longitudinal crests. Males possess an area rugosa
      composed of six ventral sagittal mamelons, a caudal extremity prolonged by a
      robust tip of the tail which is directed backwards, four pairs of genital
      papillae (two pairs lateral adanal and sessile, one pair just posterior to the
      spicule aperture, and the last pair at posterior extremity and pedunculate).
      Females possess an opisthodelphic uterus, a reflected ovary and operculate,
      unembryonated, oval eggs.

PMID- 12815220
TI  - Opecoelidae (Digenea) from western Mediterranean fishes: three rare species.
AB  - Three little-known opecoelid digeneans from marine fishes off Corsica, France,
      are redescribed and their relationships discussed. Plagioporus novella Maillard &
      Lambert, 1978 from Conger conger is transferred to Podocotyle as P. novella
      (Maillard & Lambert, 1978) n. comb. The new combinations Podocotyle tohei
      (Yamaguti, 1970) and P. congeri (Yamaguti, 1970) are formed for species
      originally assigned to Plagioporus. Podocotyle temensis Fischthal & Thomas, 1970
      from Epinephelus guaza is redescribed and compared with the other Podocotyle
      species reported from the Mediterranean. A third species, Pseudopecoeloides
      chloroscombri (Fischthal & Thomas, 1970) n. comb. (was Podocotyloides), is
      redescribed from three Trachurus species and a key to the species of this
      Pseudopecoeloides is given.

PMID- 12815221
TI  - Taxonomic revision of Tatria Kowalewski, 1904 (Cestoda: Amabiliidae):
      redescriptions of T. appendiculata Fuhrmann, 1908 and T. duodecacantha Olsen,
      1939, a key and an amended diagnosis of Tatria (sensu stricto).
AB  - Tatria appendiculata Fuhrmann, 1908 is redescribed on the basis of syntypes from
      Tachybaptus dominicus in Brazil and voucher specimens from the same host species
      in Cuba previously recorded by Rysavy & Macko (1971). Paratypes of T.
      duodecacantha Olsen, 1939 from Podilymbus podiceps in the USA are also
      redescribed and, in contrast with the opinion of Ryzhikov & Tolkacheva (1981),
      the species is recognised as valid. The major reliable diagnostic characters of
      Tatria and the distinguishing criteria applicable at the species level are re
      evaluated. An amended generic diagnosis of Tatria (sensu stricto) and an
      identification key to its constituent species are presented.

PMID- 12815222
TI  - Species of Calydiscoides Young, l969 (Monogenea: Diplectanidae Bychowsky, 1957:
      Lamellodiscinae Oliver, 1969) from nemipterid fishes off Peninsular Malaysia.
AB  - Four new species of Calydiscoides Young, 1969 are described from three species of
      nemipterids caught off Kemaman, Terengganu, on the eastern coast of Peninsular
      Malaysia: C. monogrammae n. sp. from Scolopsis monogramma; C. conus n. sp. from
      S. magaritifer; C. scolopsidis n. sp. from S. margaritifer and S. monogramma; and
      C. kemamanensis n. sp. from Pentapodus setosus. The present investigation reveals
      that the squamodiscs (lamellodiscs) are composed of 10-12 short, complete,
      interlocking and concentric tubular lamellae. The innermost lamella is attached
      to a pair of adductor muscles.

PMID- 12815223
TI  - A new species of Podocotyloides Yamaguti, 1934 (Digenea: Opecoelidae) from a
      Western Australian temperate marine fish.
AB  - A new species of Podocotyloides is described from Sillago bassensis caught off
      the coast of Western Australia. This is the second report of a species of this
      genus from Australian waters but the first of a new species. P. victori n. sp. is
      one of four species whose vitelline follicles extend into the forebody. It is
      distinguished from the other three species with vitelline follicles in the
      forebody by its relatively shorter forebody, smaller eggs and bipartite seminal
      vesicle. Pedunculotrema Fischthal & Thomas, 1970 is reduced to synonymy with
      Podocotyloides Yamaguti, 1934.

PMID- 12815224
TI  - Catalogue of genera and species of the family Chondracanthidae Milne Edwards,
      1840 (Copepoda: Poecilostomatoida) with notes on morphology.
AB  - The status of subfamilies and genera within Chondracanthidae Milne Edwards, 1840
      has recently been revised. Forty four genera are currently recognised as valid
      for the Chondracanthidae and a comprehensive catalogue to the valid genera and
      species of the family is presented here. In addition, numerous supplementary
      observations are presented on existing taxa for which incomplete or inadequate
      data were previously available.

PMID- 12815225
TI  - Gyrodactylus quadratidigitus n. sp. (Monogenea: Gyrodactylidae), a parasite of
      the leopard-spotted goby Thorogobius ephippiatus (Lowe) from the south-western
      coast of the UK.
AB  - Gyrodactylus quadratidigitus n. sp. (Monogenea, Gyrodactylidae) is described from
      the gills, fins and skin of Thorogobius ephippiatus (Lowe) (leopard-spotted goby)
      from Portland Castle Bay, Dorset, UK. G. quadratidigitus n. sp. most closely
      resembles the species of Gyrodactylus previously described by Geets from
      Pomatoschistus microps (Kroyer) in the approximate shape and size of the
      attachment hooks but can be readily distinguished from other species of the genus
      by the distinctive square shape of the toe region of the marginal hook sickle,
      the anteriorly positioned cirrus bulb and the unusually short intestinal crura
      which extend only as far as the level of the testes.

PMID- 12815226
TI  - Glycobiology in the 21st century: coming developments in glycobiology.

PMID- 12815227
TI  - Sialylglycoconjugates and sialyltransferase activity in the fungus Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a fungal pathogen associated with systemic mycoses in
      up to 10% of AIDS patients. C. neoformans yeasts express sialic acids on the cell
      wall, where they play an anti-phagocytic role, and may represent a virulence
      factor at the initial phase of infection. Since the nature of the sialic acid
      carrying components is undefined in C. neoformans, our aim in the present work
      was to identify sialylated molecules in this fungus and study the sialylation
      process. C. neoformans yeast forms were cultivated in a chemically defined medium
      free of sialic acids, to search for autologous sialylglycoconjugates. Sialylated
      glycolipids were not detected. Two glycoproteins with molecular masses of 38 and
      67 kDa were recognized by Sambucus nigra agglutinin, an alpha2,6-sialic acid
      specific lectin. The 67 kDa glycoprotein also interacted with Influenza C virus,
      but not with Limax flavus agglutinin, suggesting the presence of the 9-O
      acetylated sialic acid derivative as a constituent of the oligosaccharide chains.
      A partially purified protein fraction from cryptococcal yeast forms was able to
      transfer sialic acid from CMP-Neu5Ac to both N-(acetyl-1-(14)C)-lactosamine and
      asialofetuin. Additional evidence for a sialyltransferase in C. neoformans was
      obtained through the reactivity of fungal proteins with rabbit anti-rat alpha2,6
      sialyltransferase polyclonal antibody. Our results indicate that sialic acids in
      C. neoformans are linked to glycoproteins, which are sialylated by the action of
      a fungal sialyltransferase. This is the first demonstration of this biosynthetic
      step in pathogenic fungi.

PMID- 12815228
TI  - Characterization of the recognition of blood group B trisaccharide derivatives by
      the lectin from Marasmius oreades using frontal affinity chromatography-mass
      spectrometry.
AB  - A novel lectin from the mushroom Marasmius oreades (MOA) has been shown to bind
      to human blood group B oligosaccharides [1]. In the present work we examine the
      binding of a series of analogues of the blood group B-trisaccharide, alphaGal(1
      3)[alphaFuc(1-2)]betaGal-OR (1, R = (CH2)8COOMe). MOA was biotinylated and
      immobilized on a micro column (9.8 microL) for evaluation by Frontal Affinity
      Chromatography-Mass Spectrometry (FAC-MS) [2]. The trisaccharide 1 was found to
      be the epitope needed for maximum recognition (Kd = 3.6 microM). A series of
      synthetic deoxygenated and O-methylated analogues of the B-trisaccharide (R =
      OMe) were then screened against the lectin, and the key structural elements for
      binding were determined. OH-4 of the beta-Gal residue and OH-2 of the alpha-Gal
      residue were found to be critical for recognition. The FAC-MS technique also
      proved powerful in evaluating mixtures of compounds. Since the solution NMR
      structure and crystal structure of the B-trisaccharide are known [3], we propose
      the specific surface of the trisaccharide that is recognized by the lectin.

PMID- 12815229
TI  - Changes of the ganglioside pattern and content in human fibroblasts by high
      density cell population subculture progression.
AB  - In this study we show that the ganglioside content and pattern of human skin
      fibroblasts change along the process of cell subculture progression by varying
      the cell density. GM3, GD3 and GD1a were components of the total cell ganglioside
      mixtures extracted from cells, but GD1a was in all the extracts a minor component
      or very scant. Other gangliosides present in traces were not characterised. The
      fibroblast ganglioside content of 52 pools of cells obtained from 5 different
      cell lines cultured at variable cell density ranged from 2.0 to 13.1 nmoles per
      mg of cell protein. The molar ratio between GM3 and GD3 varied from 418 to 0.6 in
      the ganglioside mixtures, as determined by densitometric quantitative analysis
      after thin layer chromatographic separation. Both the ganglioside content and the
      GM3/GD3 molar ratio were constant along several passages of subculture
      progression performed by plating cells collected at confluence. Instead, when the
      subculture progression was performed by plating cells collected at a few days
      after reaching confluence, a progressive increase of the ganglioside content was
      observed. GD3 increased proportionally more than GM3 so that a progressive
      decrease of the ratio between GM3 and GD3 was observed. In some experiments, GD3
      was very scant at the beginning of the progression, while it was near 30% after 5
      passages under these conditions. The progressive increase of GD3 along the high
      density cell population subculture progression was associated to a moderate
      increase of the mRNA GD3 synthase.

PMID- 12815230
TI  - Two closely related forms of UDP-GlcNAc: alpha6-D-mannoside beta1,2-N
      acetylglucosaminyltransferase II occur in the clawed frog Xenopus laevis.
AB  - UDP-GlcNAc:alpha6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II (GnT II;
      EC 2.4.1.143) is a medial-Golgi resident enzyme that catalyses an essential step
      in the biosynthetic pathway leading from high mannose to complex N-linked
      oligosaccharides. Screening a cDNA library from Xenopus laevis ovary with a human
      GnT II DNA probe resulted in the isolation of two cDNA clones encoding two
      closely related GnT II isoenzymes, GnT II-A and GnT II-B. Analysis of the
      corresponding genomic DNAs revealed that the open reading frame of both X. laevis
      GnT II genes resides within a single exon. The GnT II-A gene was found to be
      transcriptionally active in all X. laevis tissues tested. In contrast, expression
      of the GnT II-B gene was detected only in a limited number of tissues. Both GnT
      II-A and GnT II-B exhibit a type II transmembrane protein topology with a
      putative N-terminal cytoplasmic tail of 9 amino acids followed by a transmembrane
      domain of 18 residues, and a C-terminal luminal domain of 405 residues. The two
      proteins differ at 28 amino acid positions within their luminal regions.
      Heterologous expression of soluble forms of the enzymes in insect cells showed
      that GnT II-A and GnT II-B are both catalytically active and exhibit similar
      specific activities. Both recombinant proteins are modified with N-linked
      oligosaccharides. N-terminal deletion studies demonstrated that the first 49
      amino acid residues are not essential for proper folding and enzymatic activity
      of X. laevis GnT II.

PMID- 12815231
TI  - Cloning and sequencing of nineteen transcript isoforms of the human alpha2,3
      sialyltransferase gene, ST3Gal III; its genomic organisation and expression in
      human tissues.
AB  - The recruitment of human peripheral blood leukocytes (PBL) to sites of infection
      and inflammation requires the surface expression of Sialyl Lewis x
      glycoconjugates (SLe(x)) on white blood cells and their interaction with E- and P
      selectins on activated endothelial cells. E-selectin has additionally been shown
      to interact with the sialyl Lewis a (SLe(a)) epitope. Human ST3Gal III codes for
      an alpha2,3-sialyltransferase involved in the biosynthesis of both SLe(a) and
      SLe(x) epitopes, although the latter with a lower efficiency. We have cloned and
      sequenced human ST3Gal III gene transcripts from human peripheral blood
      leukocytes, covering the coding region of this gene. Within our clones we
      isolated 19 different transcripts with a wide variety of deletions from 45 to 896
      nucleotides, and insertions of 26 to 173 nucleotides. Among the insertions we
      identified two new exons (E3, E6). In order to map and characterise the ST3Gal
      III gene we used the GenBank database and "computer-cloned" and characterised the
      genomic organisation of the ST3Gal III gene. The coding sequences of the ST3Gal
      III gene stretch over a gene sequence of approximately 223 Kb comprised of 15
      exons. RT-PCR and laser-induced fluorescent capillary electrophoresis (LIF-CE)
      were used to examine the expression of this gene in twenty-one human tissues,
      which showed a highly specific tissue expression pattern. Neural and muscular
      tissues showed the most complex patterns and were distinctly different from all
      other tissues examined.

PMID- 12815233
TI  - The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a
      review.
AB  - At least three proteins present in CNS myelin, Nogo, MAG and OMgp are capable of
      causing growth cone collapse and inhibiting neurite outgrowth in vitro.
      Surprisingly, Nogo and OMgp are also strongly expressed by many neurons
      (including neocortical projection cells). Nogo expression is increased by some
      cells at the borders of CNS lesion sites and by cells in injured peripheral
      nerves, but Nogo and CNS myelin are largely absent from spinal cord injury sites,
      which are none the less strongly inhibitory to axonal regeneration. Nogo is found
      on growing axons during development, suggesting possible functions for neuronal
      Nogo in axon guidance. Although Nogo, MAG and OMgp lack sequence homologies, they
      all bind to the Nogo receptor (NgR), a GPI-linked cell surface molecule which, in
      turn, binds p75 to activate RhoA. NgR is strongly expressed by cerebral cortical
      neurons but many other neurons express NgR weakly or not at all. Some neurons,
      such as DRG cells, respond to Nogo and CNS myelin in vitro although they express
      little or no NgR in vivo which, with other data, indicates that other receptors
      are available for NgR ligands. NgR expression is unaffected by injury to the
      nervous system, and there is no clear correlation between NgR expression by
      neurons and lack of regenerative ability. In the injured spinal cord,
      interactions between NgR and its ligands are most likely to be important for
      limiting regeneration of corticospinal and some other descending tracts; other
      receptors may be more important for ascending tracts. Antibodies to Nogo, mainly
      the poorly-characterised IN-1 or its derivatives, have been shown to enhance
      recovery from partial transections of the spinal cord. They induce considerable
      plasticity from the axons of corticospinal neurons, including sprouting across
      the midline and, to a limited extent, regeneration around the lesion.
      Regeneration of corticospinal axons induced by Nogo antibodies has not yet been
      demonstrated after complete transections or contusion injuries of the spinal
      cord. It is not clear whether antibodies against Nogo act on
      oligodendrocytes/myelin or by binding to neuronal Nogo, or whether they can
      stimulate regeneration of ascending axons in the spinal cord, most of which
      express little or no NgR. Despite these uncertainties, however, NgR and its
      ligands offer important new targets for enhancing plasticity and regeneration in
      the nervous system.

PMID- 12815232
TI  - Antibodies that recognize bisected complex N-glycans on cell surface
      glycoproteins can be made in mice lacking N-acetylglucosaminyltransferase III.
AB  - The bisecting GlcNAc is transferred to complex or hybrid N-glycans by the action
      of N-acetylglucosaminyltransferase III (GlcNAc-TIII) encoded by the Mgat3 gene.
      CHO cells expressing mouse GlcNAc-TIII were shown by matrix-assisted laser
      desorption ionization (MALDI) mass spectrometry to produce mainly complex N
      glycans with the predicted extra (bisecting) GlcNAc. In order to probe biological
      functions of the bisecting GlcNAc, antibodies that recognize this residue in the
      context of complex cell surface glycoconjugates were sought. The LEC10 gain-of
      function Chinese hamster ovary (CHO) cell mutant that expresses GlcNAc-TIII and
      complex N-glycans with the bisecting GlcNAc was used to immunize Mgat3(+/+) and
      Mgat3(-/-) mice. ELISA of whole sera showed that polyclonal antibodies that bound
      specifically to LEC10 cells were obtained solely from Mgat3(-/-) mice.
      Fluorescence-activated cell cytometry of different CHO glycosylation mutants and
      western blotting after glycosidase treatments were used to show that anti-LEC10
      cell antisera from Mgat3(-/-) mice recognize cellular glycoproteins with complex
      N-glycans containing both a bisecting GlcNAc and Gal residues. The polyclonal
      antibody specificity was similar to that of the lectin E-PHA. IgM-depleted serum
      containing IgG and IgA antibodies retained full binding activity. Therefore
      Mgat3(-/-) mice but not wild type mice can be used effectively to produce
      polyclonal antibodies that specifically recognize glycoproteins bearing complex N
      glycans with a bisecting GlcNAc.

PMID- 12815234
TI  - Apolipoprotein D in the Niemann-Pick type C disease mouse brain: an
      ultrastructural immunocytochemical analysis.
AB  - Enhanced apoD gene expression and abnormally high levels of apoD protein
      accumulation in the brain have been previously documented as features of the
      neurodegenerative disorder, Niemann-Pick Type C disease (NP-C). In the present
      study we have used immunocytochemistry and light and electron microscopy to
      elucidate the cellular and subcellular distribution of apoD in the Balb/c NIH
      npc1(-/-) mouse brain. The normal mouse brain demonstrates low levels of apoD
      expressing glia particularly in the cerebellar white matter. In contrast,
      abundant, strongly apoD-immunolabeled cells were observed in select grey matter
      nuclei, including the globus pallidus, thalamus, and substantia nigra, and in
      white matter tracts within the internal capsule and cerebellum of NP-C mouse
      brain. These brains regions have been previously shown to display the most
      significant neurodegenerative changes in the NP-C mouse. Ultrastructural analysis
      revealed dense apoD immunoreactivity on the nuclear envelopes of cells that have
      the morphological features of oligodendrocyte precursor-like cells and light
      staining on astrocytes. These results define the cellular and subcellular pattern
      of expression of apoD in NP-C mouse brain and suggest a possible role for this
      lipocalin in the pathophysiology of this disorder.

PMID- 12815235
TI  - Development of the nitric oxide/cGMP system in the embryonic and juvenile pond
      snail, Lymnaea stagnalis L. A comparative in situ hybridization, histochemical
      and immunohistochemical study.
AB  - Recent studies have indicated that nitric oxide (NO)-induced cGMP synthesis is
      involved in different steps of neurogenesis in invertebrates. The development of
      putative NO synthetising elements was described earlier in the embryonic and
      juvenile pond snail, Lymnaea stagnalis, applying NADPH-diaphorase histochemistry
      (Serfozo et al., 1998). In the present study, we examined the distribution of NO
      synthase (NOS) during Lymnaea development by in situ hybridization for Lymnaea
      NOS mRNA, histochemical, and immunohistochemical techniques for the NOS and NO
      stimulated cGMP. Peripheral fibers projecting to the CNS and terminating in the
      ganglionic neuropils showed NOS immunoreactivity from 85% of embryonic
      development. At the same time, a fine dot-like, immunostaining indicated the
      presence of cGMP in the neuropil area. In the CNS, Lymnaea-NOS mRNA positive, as
      well as NOS and cGMP immunoreactive perikarya were detected first during
      postembryonic development; their number significantly increased from P3 juvenile
      stage. Some of the cell groups in the CNS containing NOS immunoreactive material
      also displayed Lymnaea-NOS mRNA hybridization signal and were cGMP-positive.
      However, in the subesophageal ganglia, the distribution of Lymnaea-NOS mRNA
      positive cell groups did not correspond to that of the NOS immunoreactive cells.
      Neurons revealing transient NOS and cGMP immunoreactivity, respectively, could
      also be detected in this part of the CNS. In most of the ganglia the number of
      Lymnaea-NOS mRNA containing and cGMP immunopositive neurons, respectively,
      exceeded that of the NOS immunoreactive cells from P4 juvenile stage. The
      localization of NADPH-diaphorase reaction also correlated well with that of the
      NOS immunoreactivity in the developing CNS. At the periphery, colocalization of
      Lymnaea-NOS mRNA signal, NOS and cGMP immunoreactivities were observed in the
      epithelial cells of the esophagus and mantle after hatching. The findings suggest
      the functional maturity of the NO/cGMP signal transduction pathway at both
      central and peripheral levels during the development of the snail, Lymnaea
      stagnalis. The differences in the localization of Lymnaea-NOS mRNA labeling and
      NOS immunoreactivity in the CNS and PNS can be explained by the existence of
      different NOS isoforms, posttranslational regulation of NOS, and/or some non
      specific antibody labeling.

PMID- 12815236
TI  - Distribution of the small molecular weight GTP-binding proteins Rac1, Cdc42, RhoA
      and RhoB in the developing chick retina.
AB  - Immunohistochemistry was used to determine the distribution of Rac1, Cdc42, RhoA
      and RhoB GTPases during development of the chick retina. All proteins appear as
      early as embryonic day 5 (E5) in cells of the vitreal margin, E7-8 in cells of
      the inner third of the inner nuclear layer and E9-10 in photoreceptors. From E10
      until hatching, RhoA, Rac1 and Cdc42 were seen in perikarya and/or processes of
      amacrine, ganglion cells, and photoreceptors. Rho proteins were also observed in
      retinal Muller cells, with different distributions. RhoB showed a transient
      expression, being severely down regulated after E18. The distribution pattern of
      Rho proteins during the development of the chick retina suggests a concerted role
      in the differentiation of specific cell types, and probably during
      synaptogenesis.

PMID- 12815237
TI  - Heat shock protein 70 and heat shock protein 90 expression in light- and dark
      adapted adult octopus retinas.
AB  - Light- and dark-adaptation leads to changes in rhabdom morphology and
      photopigment distribution in the octopus retina. Molecular chaperones, including
      heat shock proteins (Hsps), may be involved in specific signaling pathways that
      cause changes in photoreceptor actin- and tubulin-based cytoskeletons and
      movement of the photopigments, rhodopsin and retinochrome. In this study, we used
      immunoblotting, in situ RT-PCR, immunofluorescence and confocal microscopy to
      localize the inducible form of Hsp70 and the larger Hsp90 in light- and dark
      adapted and dorsal and ventral halves of adult octopus retinas. The Hsps showed
      differences in distribution between the light and dark and in dorsal vs. ventral
      position in the retina. Double labeling confocal microscopy co-localized Hsp70
      with actin and tubulin, and Hsp90 with the photopigment, retinochrome. Our
      results demonstrate the presence of Hsp70 and Hsp90 in otherwise non-stressed
      light- and dark-adapted octopus retinas. These Hsps may help stabilize the
      cytoskeleton, important for rhabdom structure, and are perhaps involved in the
      redistribution of retinochrome in conditions of light and dark.

PMID- 12815238
TI  - Examining neocortical circuits: some background and facts.
AB  - The first definitive studies of where afferents to cerebral cortex terminate were
      made possible by the finding that as they degenerate axon terminals become
      electron dense. Gold toning of Golgi impregnated neurons allowed the postsynaptic
      targets of these afferents to be identified by electron microscopy and also
      allowed the termination sites of axons from a variety of types of cortical
      neurons to be ascertained, while the development of antibodies to GAD and to GABA
      made it possible to determine which types of cortical neurons are inhibitory.
      Subsequently the use of gold toned, Golgi impregnated material to examine
      neuronal connectivity was made redundant by the development of techniques that
      allowed the physiological properties of cortical neurons to be evaluated in
      neurons filled intracellularly with markers. Intracellular filling showed the
      axonal trees of cortical neurons are much more widespread than had been revealed
      by Golgi impregnations. As a result of numerous studies of the axons of
      identified neurons, we know a great deal about where most of the different types
      of neurons in cerebral cortex form their synapses, but on the other side of the
      picture there is a dearth of information about the origins of the inputs that
      specific types of cortical neurons receive. However, it is evident that each
      cortical neuron is the focus of input from many other neurons, and on the basis
      of the available data it is estimated that a single pyramidal cell in cortex
      receives its input from as many as 1,000 other excitatory neurons and as many as
      75 inhibitory neurons.

PMID- 12815239
TI  - Specificity of cortical synaptic connectivity: emphasis on perspectives gained
      from quantitative electron microscopy.
AB  - This report traces the historical development of concepts regarding the
      specificity of synaptic connectivity in the cerebral cortex as viewed primarily
      from the perspective of electron microscopy. The occurrence of stereotypical
      patterns of connection (e.g., contrasting synaptic patterns on the surfaces of
      spiny vs. non-spiny neurons, the general consistency with which axonal pathways
      impinge on and originate within specific cortical areas and layers, triadic
      synaptic relationships) implies that cortical connectivity is highly structured.
      The high degree of order characterizing many aspects of cortical organization is
      mirrored by an equally ordered arrangement of synaptic connections between
      specific types of neurons. This observation is based on quantitative electron
      microscopic studies of synapses between identified neurons and from the results
      of correlative anatomical/electrophysiological investigations. The recognition of
      recurring synaptic patterns and responses between specific neurons has generated
      increased support for the notion of specificity of synaptic connections at the
      expense of randomness, but the role of specificity in cortical function is an
      unresolved question. At the core of cortical processing lie myriad possibilities
      for computation provided by the wealth of synaptic connections involving each
      cortical neuron. Specificity, by limiting possibilities for connection, can
      impose an order on synaptic interactions even as processes of dynamic selection
      or synaptic remodeling ensure the constant formation and dissolution of cortical
      circuits. These operations make maximal use of the richness of cortical synaptic
      connections to produce a highly flexible system, irrespective of the degree of
      randomness or specificity that obtains for cortical wiring at any particular
      time.

PMID- 12815240
TI  - Specificity and non-specificity of synaptic connections within mammalian visual
      cortex.
AB  - It is clear from reviewing the findings of our own studies and those of others
      that the cerebral cortex has combined two very different strategies of
      organisation. Firstly it has a strictly defined genetically determined substrate
      of specific neurons classes, specific rules for which kinds of cells
      interconnect, a laminar architecture where efferent and afferent relays and
      interlaminar links are predetermined. But, as well, a second strategy allows
      great developmental lability in the precise spatial patterns of intralaminar
      circuits of the excitatory neurons and in the actual weights of excitatory and
      inhibitory synapses that are contributed to each neuron. This second strategy
      presumably allows the cortex to be tailor-made to the early experience of each
      individual and, as well, allow for lability of responses to different conditions
      of stimulation and adjustment of the system to compensate to some degree for
      injuries affecting afferents and circuitry in the adult system.

PMID- 12815241
TI  - Chance or design? Some specific considerations concerning synaptic boutons in cat
      visual cortex.
AB  - To understand the rules by which axons lay down their synaptic boutons we
      analyzed the linear bouton distributions in 39 neurons (23 spiny, 13 smooth) and
      3 thalamic axons, which were filled intracellularly with horseradish peroxidase
      (HRP) during in vivo experiments in cat area 17. The variation of the total
      number of boutons and the total axonal length was large (789-7,912 boutons, 12
      126 mm). The overall linear bouton density for smooth cells was higher than that
      of spiny cells and thalamic afferents (mean +/- sd, 110 +/- 21 and 78 +/- 27
      boutons per mm of axonal length). The distribution of boutons varied according to
      their location on the tree. Distal axon collaterals (first and second order
      segments in Horton-Strahler ordering) of smooth neurons had a 3.5 times higher,
      spiny cells and thalamic afferents a 2 times higher bouton density compared to
      the higher order (more proximal) segments. The distribution of interbouton
      intervals was positively skewed and similar for cells of the same type. In most
      cases a gamma-distribution fitted well, but the distributions had a tendency to
      have a heavier tail. To a first approximation these bouton distributions are
      consistent with both diffuse and specific models of interneuronal connections.
      Quite simple rules can explain these distributions and the connections between
      the different classes of neurons.

PMID- 12815242
TI  - Cell type specificity of local cortical connections.
AB  - The function of the cerebral cortex is dependent on the precise organization of
      the circuits formed by its component neurons. The connections between neurons are
      not random, but are specific at multiple levels of organization. For example,
      each cortical area connects to only a selected subset of other areas and within
      any given area the axonal and dendritic arbors of individual neurons arborize in
      precise, layer-specific patterns (for review see Felleman & Van Essen, 1991;
      Callaway, 1998). In each layer there are dendrites from multiple cell types
      including cells with somata both within and outside that layer. Anatomical
      studies have shown that axons arborizing in a particular cortical layer can
      connect selectively onto dendrites of some cell types in the layer, while
      avoiding the dendrites of other cell types (e.g. Freund & Gulyas, 1991; Hornung &
      Celio, 1992; Staiger et al., 1996). These cell type specific connections are,
      however, difficult to elucidate with anatomical methods, so the frequency of such
      specificity has remained elusive. Recent experimental methods combining
      intracellular recording of single neurons with focal neuronal stimulation by
      uncaging glutamate with light ("photostimulation") have made the analysis of cell
      type specific cortical connections more tractable. These studies show that cell
      type specificity of connections is prevalent in cortex. Here I review
      photostimulation-based studies investigating the laminar sources of cortical
      input to distinct cell types in the visual and somatosensory cortices of rats and
      the primary visual cortex of monkeys.

PMID- 12815243
TI  - Selectivity in the inter-laminar connections made by neocortical neurones.
AB  - In this brief review of inter-laminar synaptic connections in neocortex a case is
      made for the hypothesis that axons select their targets, or neurones select their
      inputs with great specificity. A large part of the data discussed was obtained
      from dual intracellular recordings in slices of adult neocortex. The neurones
      innervated in a given layer by a given type of axon were not found to be a random
      selection of the cells in that layer. Rather in a layer to layer specific
      fashion, certain types of target cells are densely innervated while others are
      not contacted or receive only weak inputs. In another layer, the same axons may
      select other targets.

PMID- 12815244
TI  - Non-uniformity of extrinsic connections and columnar organization.
AB  - Afferent columns (>200 microm in diameter) have been intensively investigated in
      the context of thalamocortical and intrinsic connections. Many extrinsic cortical
      connections also form columnar terminations, but less is known about their fine
      organization. Results from intracellular injections of neighboring neurons (in
      rats: Johnson et al., 2000) suggest that even neurons within a common domain may
      have non-stereotyped projection patterns, with only partial overlap of terminal
      arbors. The issue of non-stereotyped projections at the columnar level is further
      considered by analysis of V1 axons terminating in primate area MT/V5 (an early
      visual area), and of an axon from temporal cortex terminating in area 7b (a
      higher cortical area). Both these axons have multiple non-uniform arbors. The
      implication is that each arbor recruits different numbers and possibly different
      combinations of postsynaptic elements. While more data are needed concerning
      convergence of connectional systems, and the actual identity and numbers of
      postsynaptic targets, the distributed spatial and laminar patterns do not evoke a
      repetitive uniformity, but rather a columnar substructure and the combinatoric
      possibilities of the 3-dimensional cortical organization.

PMID- 12815245
TI  - One axon-multiple functions: specificity of lateral inhibitory connections by
      large basket cells.
AB  - The functional specificity of the projections of single large basket cells of the
      cat primary visual cortex was studied using novel analytical approaches. The
      distribution of the labelled axons and that of the target cells were three
      dimensionally reconstructed and compared quantitatively to orientation, direction
      and ocular dominance maps obtained with the intrinsic signal optical imaging
      technique. Quantitative analysis was carried out (i) for the entire basket cell,
      (ii) separately, for local and distal projections of the axon and (iii) by
      dissecting the same axon into two projection fields at the first bifurcation. It
      was found that although the functional distributions (orientation, direction and
      ocular dominance) for the entire cell were multi-modal and broadly tuned,
      individual main branches of the same cell displayed highly specific topography.
      In the further analysis, 2-dimensional probability density estimates of the
      target cell distributions revealed clear clustering which may be important for
      local subfield antagonism. These findings provide support to the idea that the
      same basket cell mediates several specific receptive field operations depending
      on the location of the target somata in the functional maps.

PMID- 12815246
TI  - Specificity in the functional architecture of primate prefrontal cortex.
AB  - Multiple lines of evidence indicate that the performance of complex cognitive
      processes, such as those involving working memory, depend upon the functional
      properties of the circuitry of the prefrontal cortex (PFC). In primates, working
      memory has been proposed to be dependent upon the sustained activity of specific
      populations of PFC pyramidal cells, with this activity regulated by certain types
      of GABAergic interneurons. Thus, knowledge of the connectivity between PFC
      pyramidal cells and interneurons is crucial to the understanding the neural
      mechanisms that subserve working memory. This paper reviews recent findings that
      reveal specificity in the spatial organization, synaptic targets and postnatal
      development of pyramidal cells and interneurons in the primate prefrontal cortex,
      and considers the relevance of these findings for the neural circuitry that
      subserves working memory.

PMID- 12815247
TI  - Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific
      GABAergic interneuron types in the rat frontal cortex.
AB  - It remains to be clarified how many classes of GABAergic nonpyramidal cells exist
      in the cortical circuit. We have divided GABA cells in the rat frontal cortex
      into 3 groups, based on their firing characteristics: fast-spiking (FS) cells,
      late-spiking (LS) cells, and non-FS cells. Expression of calcium-binding proteins
      and peptides could be shown in separate groups of GABA cells in layers II/III and
      V of the frontal cortex: (1) parvalbumin cells, (2) somatostatin cells, (3)
      calretinin and/or vasoactive intestinal polypeptide (VIP) cells [partially
      positive for cholecystokinin (CCK)] and (4) large CCK cells (almost negative for
      VIP/calretinin). Combining the physiological and chemical properties of
      morphologically diverse nonpyramidal cells allows division into several groups,
      including FS basket cells containing parvalbumin, non-FS somatostatin Martinotti
      cells with ascending axonal arbors, and non-FS large basket cells positive for
      CCK. These subtypes show characteristic spatial distributions of axon collaterals
      and the innervation tendency of postsynaptic elements. With synchronized activity
      induced by cortical excitatory or inhibitory circuits, firing patterns were also
      found to differ. Subtype-selective occurrence of electrical coupling, finding for
      potassium channel Kv3.1 proteins, and cholinergic and serotonergic modulation
      supports our tentative classification. To clarify the functional architecture in
      the frontal cortex, it is important to reveal the connectional characteristics of
      GABA cell subtypes and determine whether they are similar to those in other
      cortical regions.

PMID- 12815248
TI  - Scaling laws in the mammalian neocortex: does form provide clues to function?
AB  - Although descriptions of form have been a mainstay of comparative neuroanatomy,
      less well explored is the use of quantitative approaches, especially at the
      cellular level. In the neocortex, many gross and cellular anatomical measures
      show striking regularities over a wide range of brain sizes. Here we review our
      recent efforts to accurately characterize these scaling trends and explain them
      in functional terms. We focus on the expansion of white matter volume with
      increasing brain size and the formation of surface folds, in addition to
      principles of processing speed and energetics that may explain these phenomena.
      We also consider exceptional cases of neocortical morphology as a means of
      testing putative functional principles and developmental mechanisms. We
      illustrate this point by describing several morphological specializations at the
      cellular level that may constitute functional adaptations. Taken together, these
      approaches illustrate the benefits of a synthesis between comparative
      neuroanatomy and biophysics.

PMID- 12815249
TI  - Microstructure of the neocortex: comparative aspects.
AB  - The appearance of the neocortex, its expansion, and its differentiation in
      mammals, represents one of the principal episodes in the evolution of the
      vertebrate brain. One of the fundamental questions in neuroscience is what is
      special about the neocortex of humans and how does it differ from that of other
      species? It is clear that distinct cortical areas show important differences
      within both the same and different species, and this has led to some researchers
      emphasizing the similarities whereas others focus on the differences. In general,
      despite of the large number of different elements that contribute to neocortical
      circuits, it is thought that neocortical neurons are organized into multiple,
      small repeating microcircuits, based around pyramidal cells and their input
      output connections. These inputs originate from extrinsic afferent systems,
      excitatory glutamatergic spiny cells (which include other pyramidal cells and
      spiny stellate cells), and inhibitory GABAergic interneurons. The problem is that
      the neuronal elements that make up the basic microcircuit are differentiated into
      subtypes, some of which are lacking or highly modified in different cortical
      areas or species. Furthermore, the number of neurons contained in a discrete
      vertical cylinder of cortical tissue varies across species. Additionally, it has
      been shown that the neuropil in different cortical areas of the human, rat and
      mouse has a characteristic layer specific synaptology. These variations most
      likely reflect functional differences in the specific cortical circuits. The
      laminar specific similarities between cortical areas and between species, with
      respect to the percentage, length and density of excitatory and inhibitory
      synapses, and to the number of synapses per neuron, might be considered as the
      basic cortical building bricks. In turn, the differences probably indicate the
      evolutionary adaptation of excitatory and inhibitory circuits to particular
      functions.

PMID- 12815250
TI  - Cortical heterogeneity: implications for visual processing and polysensory
      integration.
AB  - Recent studies have revealed substantial variation in pyramidal cell structure in
      different cortical areas. Moreover, cell morphology has been shown to vary in a
      systematic fashion such that cells in visual association areas are larger and
      more spinous than those in the primary visual area. Various aspects of these
      structural differences appear to be important in influencing neuronal function.
      At the cellular level, differences in the branching patterns in the dendritic
      arbour may allow for varying degrees of non-linear compartmentalisation.
      Differences in total dendritic length and spine number may determine the number
      of inputs integrated by individual cells. Variations in spine density and
      geometry may affect cooperativity of inputs and shunting inhibition, and the
      tangential dimension of the dendritic arbours may determine sampling strategies
      within cortex. At the systems level, regional variation in pyramidal cell
      structure may determine the degree of recurrent excitation through reentrant
      circuits influencing the discharge properties of individual neurones and the
      functional signature of the circuits they compose. The ability of pyramidal
      neurones in visual areas of the parietal and temporal lobes to integrate large
      numbers of excitatory inputs may also facilitate cortical binding. Here I
      summarise what I consider to be among the most salient, and testable, aspects of
      an inter-relationship between morphological and functional heterogeneity in
      visual cortex.

PMID- 12815251
TI  - Cortical area and species differences in dendritic spine morphology.
AB  - Dendritic spines receive most excitatory inputs in the neocortex and are
      morphologically very diverse. Recent evidence has demonstrated linear
      relationships between the size and length of dendritic spines and important
      features of its synaptic junction and time constants for calcium
      compartmentalisation. Therefore, the morphologies of dendritic spines can be
      directly interpreted functionally. We sought to explore whether there were
      potential differences in spine morphologies between areas and species that could
      reflect potential functional differences. For this purpose, we reconstructed and
      measured thousands of dendritic spines from basal dendrites of layer III
      pyramidal neurons from mouse temporal and occipital cortex and from human
      temporal cortex. We find systematic differences in spine densities, spine head
      size and spine neck length among areas and species. Human spines are
      systematically larger and longer and exist at higher densities than those in
      mouse cortex. Also, mouse temporal spines are larger than mouse occipital spines.
      We do not encounter any correlations between the size of the spine head and its
      neck length. Our data suggests that the average synaptic input is modulated
      according to cortical area and differs among species. We discuss the implications
      of these findings for common algorithms of cortical processing.

PMID- 12815252
TI  - Barrels, stripes, and fingerprints in the brain - implications for theories of
      cortical organization.
AB  - In the last decade improvements in the histological processing of cortical tissue
      in conjunction with the investigation of additional mammalian species in
      comparative brain studies has expanded the information available to guide
      theories of cortical organization. Here I review some of these recent findings in
      the somatosensory system with an emphasis on modules related to specializations
      of the peripheral sensory surface. The diversity of modular representations, or
      cortical "isomorphs" suggest that information from the sensory sheet guides many
      of the features of cortical maps and suggest that cortex is not constrained to
      form circular units in the form of a traditional cortical column.

PMID- 12815253
TI  - The inferior temporal cortex: architecture, computation, and representation.
AB  - Neurons in the inferior temporal cortex (IT), an area crucially involved in
      visual object recognition in monkeys, show the visual response properties and
      anatomical/chemical nature which are distinct from those in the cortical areas
      that feed visual inputs to the IT. Earlier physiological studies showed that IT
      neurons have large receptive fields covering the center and contralateral (often
      bilateral) visual fields, stimulus selectivity for images of complex objects or
      shapes, and translation invariance of the stimulus selectivity. Recent studies
      have revealed new aspects of their properties such as invariant selectivity for
      shapes despite drastic changes in various physical attributes of stimuli, latent
      excitatory inputs masked by stimulus-specific GABAergic inhibition, selectivity
      for binocular disparity and 3-dimensional surface structures, profound effects of
      learning on the stimulus selectivity, and columnar clustering of neurons with
      similar stimulus selectivity for shapes and other object features. Another line
      of research using histological techniques have revealed that pyramidal neurons in
      the IT are larger in the size of dendritic arbors, in the number of dendritic
      branches and spines, and in the size and distribution of horizontal axonal arbors
      than those in the earlier areas, allowing them to integrate a larger population
      of afferents and process more diverse inputs. The concentration of several
      neurochemicals including those related to synaptic transmission or plasticity
      changes systematically towards the IT along the occipitotemporal pathway. Many of
      the characteristics of IT neurons parallel or explain certain aspects of visual
      object perception, although the behavioral relevance has yet to be addressed
      experimentally.

PMID- 12815254
TI  - Frontal lobe and cognitive development.
AB  - In phylogeny as in ontogeny, the association cortex of the frontal lobe, also
      known as the prefrontal cortex, is a late-developing region of the neocortex. It
      is also one of the cortical regions to undergo the greatest expansion in the
      course of both evolution and individual maturation. In the human adult, the
      prefrontal cortex constitutes as much as nearly one-third of the totality of the
      neocortex. The protracted, relatively large, development of the prefrontal cortex
      is manifest in gross morphology as well as fine structure. In the developing
      individual, its late maturation is made most apparent by the late myelination of
      its axonal connections. This and other indices of morphological development of
      the prefrontal cortex correlate with the development of cognitive functions that
      neuropsychological studies in animals and humans have ascribed to this cortex. In
      broad outline, the ventromedial areas of the prefrontal cortex, which with
      respect to other prefrontal areas develop relatively early, are involved in the
      expression and control of emotional and instinctual behaviors. On the other hand,
      the late maturing areas of the lateral prefrontal convexity are principally
      involved in higher executive functions. The most general executive function of
      the lateral prefrontal cortex is the temporal organization of goal-directed
      actions in the domains of behavior, cognition, and language. In all three
      domains, that global function is supported by a fundamental role of the lateral
      prefrontal cortex in temporal integration, that is, the integration of temporally
      discontinuous percepts and neural inputs into coherent structures of action.
      Temporal integration is in turn served by at least three cognitive functions of
      somewhat different prefrontal topography: working memory, preparatory set, and
      inhibitory control. These functions engage the prefrontal cortex in interactive
      cooperation with other neocortical regions. The development of language
      epitomizes the development of temporal integrative cognitive functions and their
      underlying neural substrate, notably the lateral prefrontal cortex and other late
      developing cortical regions.

PMID- 12815255
TI  - Neocortical circuits: evolutionary aspects and specificity versus non-specificity
      of synaptic connections. Remarks, main conclusions and general comments and
      discussion.

PMID- 12815256
TI  - Assessing the effects of time and spatial averaging in 15N chemical shift/15N-1H
      dipolar correlation solid state NMR experiments.
AB  - The effect of time and spatial averaging on (15)N chemical shift/(1)H-(15)N
      dipolar correlation spectra, i.e., PISEMA spectra, of alpha-helical membrane
      peptides and proteins is investigated. Three types of motion are considered: (a)
      Librational motion of the peptide planes in the alpha-helix; (b) rotation of the
      helix about its long axis; and (c) wobble of the helix about a nominal tilt
      angle. A 2ns molecular dynamics simulation of helix D of bacteriorhodopsin is
      used to determine the effect of librational motion on the spectral parameters.
      For the time averaging, the rotation and wobble of this same helix are modelled
      by assuming either Gaussian motion about the respective angles or a uniform
      distribution of a given width. For the spatial averaging, regions of possible
      (15)N chemical shift/(1)H-(15)N dipolar splittings are computed for a
      distribution of rotations and/or tilt angles of the helix. The computed spectra
      show that under certain motional modes the (15)N chemical shift/(1)H-(15)N
      dipolar pairs for each of the residues do not form patterns which mimic helical
      wheel patterns. As a result, the unambiguous identification of helix tilt and
      helix rotation without any resonance assignments or on the basis of a single
      assignment may be difficult.

PMID- 12815257
TI  - Overall structure and sugar dynamics of a DNA dodecamer from homo- and
      heteronuclear dipolar couplings and 31P chemical shift anisotropy.
AB  - The solution structure of d(CGCGAATTCGCG)(2) has been determined on the basis of
      an exceptionally large set of residual dipolar couplings. In addition to the
      heteronuclear (13)C-(1)H and (15)N-(1)H and qualitative homonuclear (1)H-(1)H
      dipolar couplings, previously measured in bicelle medium, more than 300
      quantitative (1)H-(1)H and 22 (31)P-(1)H dipolar restraints were obtained in
      liquid crystalline Pf1 medium, and 22 (31)P chemical shift anisotropy restraints.
      High quality DNA structures can be obtained solely on the basis of these new
      restraints, and these structures are in close agreement with those calculated
      previously on the basis of (13)C-(1)H and (15)N-(1)H dipolar couplings. In the
      newly calculated structures, (31)P-(1)H dipolar and (3)JsubH3(')Psub couplings
      and (31)P CSA data restrain the phosphodiester backbone torsion angles. The final
      structure represents a quite regular B-form helix with a modest bending of
      approximately 10 degrees, which is essentially independent of whether or not
      electrostatic terms are used in the calculation. Combined, the number of homo-
      and heteronuclear dipolar couplings significantly exceeds the number of degrees
      of freedom in the system. Results indicate that the dipolar coupling data cannot
      be fit by a single structure, but are compatible with the presence of rapid
      equilibria between C2(')-endo and C3(')-endo deoxyribose puckers (sugar
      switching). The C2(')-H2(')/H2(") dipolar couplings in B-form DNA are
      particularly sensitive to sugar pucker and yield the largest discrepancies when
      fit to a single structure. To resolve these discrepancies, we suggest a
      simplified dipolar coupling analysis that yields N/S equilibria for the ribose
      sugar puckers, which are in good agreement with previous analyses of NMR J(HH)
      couplings, with a population of the minor C3(')-endo form higher for pyrimidines
      than for purines.

PMID- 12815258
TI  - Efficient expression of isotopically labeled peptides for high resolution NMR
      studies: application to the Cdc42/Rac binding domains of virulent kinases in
      Candida albicans.
AB  - The production of bioactive peptides and small protein fragments is commonly
      achieved via solid-phase chemical synthesis. However, such techniques become
      unviable and prohibitively expensive when the peptides are large (e.g., >30 amino
      acids) or when isotope labeling is required for NMR studies. Expression and
      purification of large quantities of unfolded peptides in E. coli have also proved
      to be difficult even when the desired peptides are carried by fusion proteins
      such as GST. We have developed a peptide expression system that utilizes a novel
      fusion protein (SFC120) which is highly expressed and directs the peptides to
      inclusion bodies, thereby minimizing in-cell proteolysis whilst maintaining high
      yields of peptide expression. The expressed peptides can be liberated from the
      carrier protein by CNBr cleavage at engineered methionine sites or through
      proteolysis by specific proteases for peptides containing methionine residues. In
      the present systems, we use CNBr, due to the absence of methionine residues in
      the target peptides, although other cleavage sites can be easily inserted. We
      report the production of six unfolded protein fragments of different composition
      and lengths (19 to 48 residues) derived from the virulent effector kinases, Cla4
      and Ste20 of Candida albicans. All six peptides were produced with high yields of
      purified material (30-40 mg/l in LB, 15-20 mg/l in M9 medium), pointing to the
      general applicability of this expression system for peptide production. The
      enrichment of these peptides with (15)N, (15)N/(13)C and even (15)N/(13)C/(2)H
      isotopes is presented allowing speedy assignment of poorly-resolved resonances of
      flexible peptides.

PMID- 12815259
TI  - Structure and dynamics of a membrane protein in micelles from three solution NMR
      experiments.
AB  - Three solution NMR experiments on a uniformly (15)N labeled membrane protein in
      micelles provide sufficient information to describe the structure, topology, and
      dynamics of its helices, as well as additional information that characterizes the
      principal features of residues in terminal and inter-helical loop regions. The
      backbone amide resonances are assigned with an HMQC-NOESY experiment and the
      backbone dynamics are characterized by a (1)H-(15)N heteronuclear NOE experiment,
      which clearly distinguishes between the structured helical residues and the more
      mobile residues in the terminal and interhelical loop regions of the protein. The
      structure and topology of the helices are described by Dipolar waves and PISA
      wheels derived from experimental measurements of residual dipolar couplings
      (RDCs) and residual chemical shift anisotropies (RCSAs). The results show that
      the membrane-bound form of Pf1 coat protein has a 20-residue trans-membrane
      hydrophobic helix with an orientation that differs by about 90 degrees from that
      of an 8-residue amphipathic helix. This combination of three-experiments that
      yields Dipolar waves and PISA wheels has the potential to contribute to high
      throughput structural characterizations of membrane proteins.

PMID- 12815261
TI  - NMR experiments for the measurement of proton-proton and carbon-carbon residual
      dipolar couplings in uniformly labelled oligosaccharides.
AB  - A 2D-HSQC-carbon selective/proton selective-constant time COSY, 2D-HSQC-(sel C,
      sel H)-CT COSY experiment, which is applicable to uniformly (13)C isotopically
      enriched samples (U-(13)C) of oligosaccharides or oligonucleotides is proposed
      for the measurement of proton-proton RDC in crowded regions of 2D-spectra. In
      addition, a heteronuclear constant time-COSY experiment, (13)C-(13)C CT-COSY, is
      proposed for the measurement of one bond carbon-carbon RDC in these molecules.
      These two methods provide an extension, to U-(13)C molecules, of the original
      homonuclear constant time-COSY experiment proposed by Tian et al. (1999) for
      saccharides. The combination of a number of these RDC with NOE data may provide
      the method of choice to study oligosaccharide conformation in the free and
      receptor-bound state.

PMID- 12815260
TI  - IBIS--a tool for automated sequential assignment of protein spectra from triple
      resonance experiments.
AB  - We have developed a tool for computer-assisted assignments of protein NMR spectra
      from triple resonance data. The program is designed to resemble established
      manual assignment procedures as closely as possible. IBIS exports its results in
      XEASY format. Thus, using IBIS the operator has continuous visual and accounting
      control over the progress of the assignment procedure. IBIS achieves complete
      assignments for those residues that exhibit sequential triple resonance
      connectivities within a few hours or days.

PMID- 12815262
TI  - A use of Ramachandran potentials in protein solution structure determinations.
AB  - A strategy is developed to use database-derived phi-psi constraints during
      simulated annealing procedures for protein solution structure determination in
      order to improve the Ramachandran plot statistics, while maintaining the
      agreement with the experimental constraints as the sole criterion for the
      selection of the family. The procedure, fully automated, consists of two
      consecutive simulated annealing runs. In the first run, the database-derived phi
      psi constraints are enforced for all amino acids (but prolines and glycines). A
      family of structures is then selected on the ground of the lowest violations of
      the experimental constraints only, and the phi-psi values for each residue are
      examined. In the second and final run, the database-derived phi-psi constraints
      are enforced only for those residues which in the first run have ended in one and
      the same favored phi-psi region. For residues which are either spread over
      different favored regions or concentrated in disallowed regions, the constraints
      are not enforced. The final family is then selected, after the second run, again
      only based on the agreement with the experimental constraints. This automated
      approach was implemented in DYANA and was tested on as many as 12 proteins,
      including some containing paramagnetic metals, whose structures had been
      previously solved in our laboratory. The quality of the structures, and of
      Ramachandran plot statistics in particular, was notably improved while preserving
      the agreement with the experimental constraints.

PMID- 12815263
TI  - Amino-acid-type selective isotope labeling of proteins expressed in Baculovirus
      infected insect cells useful for NMR studies.
AB  - Culture conditions for successful amino-acid-type selective isotope labeling of
      proteins expressed in Baculovirus-infected insect cells are described. The method
      was applied to the selective labeling of the catalytic domain of c-Abl kinase
      with (15)N-phenylalanine, (15)N-glycine, (15)N-tyrosine or (15)N-valine. For the
      essential amino acids phenylalanine, tyrosine and valine high (15)N-label
      incorporation rates of >/=90% and approximately the expected number of resonances
      in the HSQC spectra were observed, which was not the case for the non-essential
      amino acid glycine. The method should be applicable to amino-acid-type selective
      isotope labeling of other recombinant proteins which have not been amenable to
      NMR analysis.

PMID- 12815264
TI  - Rapid backbone 1H, 13C, and 15N assignment of the V1 domain of human PKC iota
      using the new program IBIS.

PMID- 12815265
TI  - Sequence-specific assignment of the B-Myb DNA-binding domain (B-MybR2R3) bound to
      a 16 base-pair DNA target site corresponding to a regulatory site from the tom-1
      gene.

PMID- 12815266
TI  - Backbone 1H, 13C and 15N resonance assignments for the 25.8 kDa DNA binding
      domain of the human p63 protein.

PMID- 12815267
TI  - Assignment of the 1H, 13C and 15N resonances of the catalytic domain of guanine
      nucleotide exchange factor SopE2 from Salmonella dublin.

PMID- 12815268
TI  - 1H, 15N and 13C resonance assignments of the tetratricopeptide repeat (TPR)
      domain of hSGT.

PMID- 12815269
TI  - Treatment issues pertaining to pathological gamblers with a comorbid disorder.
AB  - Evidence of an increased risk for various psychiatric disorders among
      pathological gamblers far exceeds our understanding of the impact that this
      psychiatric comorbidity has on the outcome of treatment for pathological
      gambling. One major source of the problem is that treatment efficacy and
      effectiveness studies for pathological gambling typically have not addressed
      comorbidity's impact on outcome. This paper discusses epidemiological, clinical,
      health service delivery, and research issues pertaining to the intersection of
      pathological gambling treatment outcome and comorbid psychiatric disorders. It is
      argued that this topic suffers from major knowledge gaps in terms of the nature
      of comorbidity of pathological gambling and other psychiatric disorders and the
      role of client characteristics on treatment outcome for pathological gambling.
      Research priorities are identified.

PMID- 12815270
TI  - The role of natural recovery in alcoholism and pathological gambling.
AB  - While most pathological gamblers, like most alcohol abusers, recover on their
      own, it seems likely that they are at greater risk for relapse than those who
      have been through successful treatment. Accordingly, a substantial increase in
      treatment resources for pathological gamblers, along with greater efforts to
      establish the effectiveness of these treatments, ought to receive national
      priority. If the data on alcohol-abusing self-changers are generalizable to self
      changing pathological gamblers, the prognosis for gamblers who stop gambling all
      together is better than for those who aspire to controlled or nonproblem
      gambling. While pathological gamblers with comorbid substance abuse are more
      difficult to treat than those without it, the impact of comorbid substance abuse
      on the decision by pathological gamblers to change has not yet been explored,
      although it should be. Similarly, the impact of other Axis I pathology on
      pathological gambling self-change, especially depression and anxiety, should be
      thoroughly explored. The most pressing problem in this field appears to be
      definitional. As a consequence, until consensus is reached on a reliable, valid,
      and useful classification scheme for pathological gambling, both research and
      clinical efforts will continue to suffer.

PMID- 12815271
TI  - Some theoretical models and constructs generic to substance abuse prevention
      programs for adolescents: possible relevance and limitations for problem
      gambling.
AB  - For the past several years the author and his colleagues have explored the area
      of how social psychological constructs and theoretical models can be applied to
      the prevention of health threatening behaviors in adolescents. In examining the
      need for the development of gambling prevention programs for adolescents, it
      might be of value to consider the application of such constructs and theoretical
      models as a foundation to the development of prevention programs in this emerging
      problem behavior among adolescents. In order to provide perspective to the
      reader, the present paper reviews the history of various psychosocial models and
      constructs generic to programs directed at prevention of substance abuse in
      adolescents. A brief history of some of these models, possibly most applicable to
      gambling prevention programs, are presented. Social inoculation, reasoned action,
      planned behavior, and problem behavior theory, are among those discussed. Some
      deficits of these models, are also articulated. How such models may have
      relevance to developing programs for prevention of problem gambling in
      adolescents is also discussed. However, the inherent differences between gambling
      and more directly health threatening behaviors such as substance abuse must, of
      course, be seriously considered in utilizing such models. Most current gambling
      prevention programs have seldom been guided by theoretical models. Developers of
      gambling prevention programs should consider theoretical foundations,
      particularly since such foundations not only provide a guide for programs, but
      may become critical tools in evaluating their effectiveness.

PMID- 12815272
TI  - The self-exclusion program: legal and clinical considerations.
AB  - In recent years, attention focused on compulsive gambling(1), and its causes and
      cures, has increased at a notable rate. Among the measures taken to help the
      compulsive gambler is the voluntary(2) self-exclusion program which is either in
      place or being considered in various states.(3) Although the programs differ from
      jurisdiction to jurisdiction, the basic premise is that the gambler requests that
      he be banned from the gaming establishment and/or removed from its mailing list.
      This article examines this new concept primarily from a legal perspective. The
      self-exclusion program represents a state-created legal entity constructed upon a
      clinical foundation. It prominently includes several clinical references to
      mental health principles. Of necessity, there appear some analogies to the field
      of substance abuse; these have provided at least a starting point for more
      particularized study and research in the fledgling field of compulsive gambling
      treatment.

PMID- 12815273
TI  - How to design an effective treatment outcome study.
AB  - This paper provides a "how to" guide for designing an effective treatment outcome
      study. Three areas addressed are (1) a description of the three stages: treatment
      development, efficacy testing, and effectiveness testing; (2) suggestions for
      writing a grant proposal; and (3) optimal study design. The latter includes
      considerations of comorbidity, standard design features, treatment, assessment,
      patients, therapists, and replication. These are discussed with regard to the
      testing of psychosocial treatments, with examples from the area of pathological
      gambling. Finally, general questions applicable to any study are provided,
      including: Is there a rationale for all design decisions? Is the investigator
      aware of what can and cannot be inferred from the data, based on the design? Does
      the study design address research questions that are important and genuinely of
      benefit to the field?

PMID- 12815274
TI  - Mad dogs, Englishmen and apoptosis: the role of cell death in UV-induced skin
      cancer.
AB  - Apoptosis plays a critical role in the development and progression of ultraviolet
      induced skin cancers. In particular, Fas and Fas ligand (FasL) interactions are
      known to control the development of "sunburn cells" or apoptotic keratinocytes in
      the UV-exposed epidermis. In the absence of functional Fas/FasL signaling, UV
      induced apoptosis is diminished and mutations rapidly accumulate. UV-induced
      suppression of host immunity, a process regulating skin cancer outgrowth, is also
      controlled through Fas/FasL interactions. Other death receptors, such as the
      receptor for tumor necrosis factor, may also contribute to UV-induced
      carcinogenesis and progression. Understanding the involvement of cell death in
      cancers caused by exposure to sunlight may provide novel approaches for
      prevention and therapy of these ever-increasing malignancies.

PMID- 12815275
TI  - Leptin-induced adipose apoptosis: Implications for body weight regulation.
AB  - Great strides have been made in understanding the genetics of body weight
      regulation, in part due to the study of rodent models of obesity that are
      characterized by mutations affecting leptin or its receptors. Leptin, produced in
      adipose tissue, acts both centrally and peripherally to orchestrate complex
      metabolic and behavioral changes that increase loss of adipose tissue, including
      suppressing food intake and increasing thermogenesis. In addition, recent
      evidence indicates that leptin acts centrally to trigger an apoptotic process
      resulting in adipocyte deletion. Loss of adipocytes by apoptosis may provide an
      explanation for the unexpected delay in return to initial energy status following
      leptin treatments. This review summarizes the major aspects of leptin-induced
      adipose tissue apoptosis, including some of the newest findings about possible
      mechanisms of action.

PMID- 12815276
TI  - Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic
      implications.
AB  - Multiple myeloma (MM), a hematologic malignancy, remains fatal despite all
      available therapies. Initial treatment with conventional drugs effectively
      induces MM cell death/apoptosis; however, prolonged drug exposures results in the
      development of de novo chemoresistance. Because MM is a bone marrow (BM) cancer,
      the progression of disease and drug efficacy is highly influenced by the BM
      microenvironment. Novel agents, such as proteasome inhibitors (PS-341), 2
      methoxyestradiol (2ME2), thalidomide and its immunomodulatory derivatives
      (IMiDs), and histone deacetylase (HDAC) inhibitors target the MM cell in its BM
      microenvironment; thereby enhancing anti-MM activity as well as preventing
      development of drug-resistance. The transcriptional events and signaling
      pathways, which mediate these responses in MM cells are now being delineated, and
      may serve to identify novel therapeutic targets based upon interrupting MM cell
      growth or triggering MM cell death.

PMID- 12815277
TI  - Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic
      properties.
AB  - In recent years, several inhibitors that prevent caspase activation and apoptosis
      have emerged. At high doses, however, these inhibitors can have nonspecific
      effects and/or become cytotoxic. In this study, we determined the effectiveness
      of broad spectrum caspase inhibitors to prevent apoptosis. A carboxy terminal
      phenoxy group conjugated to the amino acids valine and aspartate (Q-VD-OPh)
      potently inhibited apoptosis. Q-VD-OPh was significantly more effective in
      preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk, and
      was also equally effective in preventing apoptosis mediated by the three major
      apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. In addition to the
      increased effectiveness, Q-VD-OPh was not toxic to cells even at extremely high
      concentrations. Our data indicate that the specificity, effectiveness, and
      reduced toxicity of caspase inhibitors can be significantly enhanced using
      carboxyterminal o-phenoxy groups and may have important uses in vivo.

PMID- 12815278
TI  - Identification of the primary caspase 3 cleavage site in alpha II-spectrin during
      apoptosis.
AB  - Alpha II-spectrin is one of the major proteins responsible for maintaining the
      cytoskeletal integrity of the cell. The caspase 3-mediated cleavage of alpha II
      spectrin during apoptotic cell death may play an important role in altering
      membrane stability and the formation of apoptotic bodies. In this study, we
      identified the primary caspase 3 cleavage site in alpha II-spectrin. We found
      that the transcriptional inhibitor, actinomycin D, induced caspase 3 activation
      and that caspase 3 activation is coincident with the cleavage of alpha II
      spectrin protein at a primary cleavage site. Deletion analysis and site directed
      mutagenesis identified the primary cleavage site in alpha II spectrin at amino
      acid 1185 (DETD). The primary caspase 3 cleavage site in alpha II spectrin is
      conserved in immature and mature B cells. Our results indicate that alpha II
      spectrin is initially cleaved at a caspase 3 consensus site and this primary
      event likely alters the structural conformation of the protein exposing
      subsequent cleavage sites and altering cytoskeletal integrity. Identification of
      the primary cleavage site for caspase 3 may help to elucidate the role of alpha
      II-spectrin in membrane stability and apoptosis as well as provide new insights
      into alpha II-spectrin autoantibody formation associated with the autoimmune
      disease, Sjogren's syndrome.

PMID- 12815279
TI  - Caspase-3 activation is an early event and initiates apoptotic damage in a human
      leukemia cell line.
AB  - Many apoptotic pathways culminate in the activation of caspase cascades usually
      triggered by the apical caspases-8 or -9. We describe a paradigm where apoptosis
      is initiated by the effector caspase-3. Diethylmaleate (DEM)-induced apoptotic
      damage in Jurkat cells was blocked by the anti-apoptotic protein Bcl-2, whereas,
      a peptide inhibitor of caspase-3 but not caspase-9 blocked DEM-induced
      mitochondrial damage. Isogenic Jurkat cell lines deficient for caspase-8 or the
      adaptor FADD (Fas associated death domain) were not protected from DEM-induced
      apoptosis. Caspase-3 activation preceded that of caspase-9 and initial processing
      of caspase-3 was regulated independent of caspase-9 and Bcl-2. However,
      inhibitors of caspase-9 or caspase-6 regulated caspase-3 later in the pathway. We
      explored the mechanism by which caspase-3 processing is regulated in this system.
      DEM triggered a loss of Erk-1/2 phosphorylation and XIAP (X-linked inhibitor of
      apoptosis protein) expression. The phorbol ester PMA activated a MEK-dependent
      pathway to block caspase-3 processing and cell death. Constitutively active MEK-1
      (CA-MEK) upregulated XIAP expression and exogenous XIAP inhibited DEM-induced
      apoptotic damage. Thus, we describe a pathway where caspase-3 functions to
      initiate apoptotic damage and caspase-9 and caspase-6 amplify the apoptotic
      cascade. Further, we show that MEK may regulate caspase-3 activation via the
      regulation of XIAP expression in these cells.

PMID- 12815280
TI  - Sequence-based discovery of a synthetic peptide inhibitor of caspase 6.
AB  - We recently demonstrated that tumor necrosis factor alpha activates caspase 6,
      which in turn cleaves transcription factor AP-2 alpha. We mapped the cleavage
      site at 19 amino acids from the N-terminus at the sequence aspartate-argenine
      histidine-aspartate (DRHD). Mutating aspartic acid at position 19 abrogated the
      cleavage site. From these observations, we hypothesized that the DRHD peptide
      could act as a caspase 6 inhibitor. To test this hypothesis, the peptide
      zAsp(Ome)-Arg-His-Asp(Ome)-fluoromethyl ketone (zDRHDfmk) was synthesized. Here
      we show that zDRHDfmk inhibits TNFalpha-induced caspase 6 activity and apoptosis
      in breast cancer cells. When compared to other caspase inhibitors, zDRHDfmk
      inhibited caspase 6 activity more effectively than the general caspase inhibitor
      zVal-Ala-Lys(Ome)-fluoromethy ketone (zVADfmk) or the caspase 6 inhibitor zVal
      Glu-Ile-Asp-(Ome)-fluoromethyl ketone (zVEIDfmk). However, it was less effective
      in inhibiting TNFalpha-induced apoptosis than zVADfmk or zVEIDfmk, presumably
      because caspase 6 is only one of at least three effector caspases, the others
      being caspase 3 and 7, that are active during caspase-dependent apoptosis. The
      discovery of this sequence-based caspase 6 inhibitor provides a new tool for
      studying caspase 6. More importantly, it could be used, in combination with other
      agents, as a drug to inhibit apoptosis in neurodegenrative diseases such as
      Alzheimer's, Parkinson and amyotrophic lateral sclerosis.

PMID- 12815281
TI  - cDNA array analysis of alterations in gene expression in the promyelocytic
      leukemia cell line, HL-60, after apoptosis induction with etoposide.
AB  - Alterations in gene expression during apoptosis in HL-60 cells were identified by
      a cDNA based array analysis. Apoptosis was induced in the human promyelocytic
      leukemia cell line, HL-60, by incubation with 30 microM etoposide for 5 hours.
      Changes in gene expression occurring during apoptosis in these cells were
      detected using the "ATLAS cDNA Expression Array" technique. 40 genes were
      identified as differentially expressed in the apoptotic cells by at least a
      factor of two. 30 of these genes were down-regulated during apoptosis. Many of
      the down-regulated genes reflected decreased proliferative activity in the cells
      as well as decreased activity of survival pathways. Most of the genes, which were
      up-regulated during apoptosis, were genes involved in pathways leading to cell
      death and suppression of proliferation. Based on the up-regulations observed at
      the mRNA level, it is speculated that etoposide-induced apoptosis in the HL-60
      cells proceeds via pathways involving factors such as TNFalpha, IGFBP3, SAPK1, AP
      1 and GADD153/CHOP10. Four genes, which showed changes at the mRNA level, were
      also analyzed by Western blotting in order to confirm the observed differences at
      the protein level.

PMID- 12815282
TI  - The role of sFRP4, a secreted frizzled-related protein, in ovulation.
AB  - Ovulation is a complex, multi-factorial event that involves the degeneration of a
      specific area of the follicular and ovarian surface via apoptosis. Many apoptosis
      related genes have been identified in the ovary. Secreted Frizzled Related
      Protein 4 (sFRP4) is a protein that appears to antagonize a molecular pathway for
      cell survival. sFRP4 gene expression is known to be upregulated with apoptosis in
      the ovarian corpus luteum. In this study, ovulation was hormonally induced in
      immature Wistar rats and their ovaries collected for analysis of apoptosis and
      sFRP4. TUNEL staining identified a greater amount of dying cells in the thecal
      layer of treated rat ovaries compared to controls. The results of 3'-end
      labelling revealed a significant increase (p < 0.01) in apoptosis at 12 hours
      following treatment compared to other time points and control. In situ
      hybridization exhibited a visible increase in amounts of sFRP4 mRNA expression in
      the thecal layers of follicles from treated rats compared to controls.
      Quantitative RT-PCR revealed no significant difference in sFRP4 expression levels
      between treated and control tissues although a clear trend towards an increase
      was observed in the treated group. This study demonstrates an association between
      sFRP4 and apoptosis in rat ovulation.

PMID- 12815283
TI  - Inhibition of topoisomerase II overrides the G2/M check points of the cell cycle
      in EBV-lymphocytes.
AB  - Epstein-Barr virus (EBV) is associated with a number of human malignancies. In
      vitro EBV infection transforms human lymphocytes into proliferating cell lines
      (EBV-lymphocytes). Etoposide, topoisomerase II inhibitor, induced apoptosis in
      EBV-lymphocytes as shown by expression of phosphatidylserine, loss of DNA and
      mitochondrial membrane potential, and cell shrinkage. In contrast, those cells,
      which had yet to display signs of apoptosis, grew to exceed their normal size.
      These EBV-lymphocytes had unusual cellular and nuclear morphology, higher
      mitochondrial membrane potential, increased expression of proteins and an amount
      of DNA that exceeded the maximum DNA content in normal EBV-lymphocytes by more
      than two-fold. Application of the caspase inhibitor Z-VAD-FMK in the presence of
      etoposide increased the numbers of such large cells. This data suggests that
      inhibition of topoisomerase II by etoposide does not inhibit DNA synthesis but
      rather overrides the G(2)/M check points of the cell cycle, resulting in cells
      growth over their genetically determined size. This may trigger apoptosis to
      eliminate cells, which failed to complete mitosis.

PMID- 12815284
TI  - Flow cytometry, an overview.

PMID- 12815285
TI  - High resolution flow cytometric analysis of electronic nuclear volume and DNA
      content in normal and abnormal human tissue.
AB  - BACKGROUND: The NPE Analyzer flow cytometer can simultaneously analyze the
      electronic nuclear volume (ENV) and DNA content of cells. This study describes
      the schematics, resolution, reproducibility, and sensitivity of biological
      standards analyzed on this unit. METHODS: Calibrated beads and biological
      standards (lymphocytes, trout erythrocytes [TRBC], calf thymocytes, and tumor
      cells) were analyzed for ENV versus DNA content. Parallel data (forward scatter
      versus DNA) from a conventional flow cytometer were obtained. RESULTS: ENV
      linearity studies yielded an R value of 0.999. TRBC had a coefficient of
      variation (CV) of 1.18 +/- 0.13. DNA indexes as low as 1.02 were detectable. DNA
      content of lymphocytes from 42 females was 1.9% greater than that for 60 males,
      with a noninstrumental variability in total DNA content of 0.5%. The ENV/DNA
      ratio was constant in 15 normal human tissue samples, but differed in the four
      animal species tested. The ENV/DNA ratio for a hypodiploid breast carcinoma was
      2.3 times greater than that for normal breast tissue. CONCLUSIONS: The high
      resolution ENV versus DNA analyses are highly reliable, sensitive, and can be
      used for the detection of near-diploid tumor cells that are difficult to identify
      with conventional cytometers. ENV/DNA ratio may be a useful parameter for
      detection of aneuploid populations.

PMID- 12815286
TI  - Analysis of heterogeneous red cell populations by flow cytometry.

PMID- 12815287
TI  - Chromosome sorting and genomics.

PMID- 12815288
TI  - Analysis of intracellular cytokines using flowcytometry.
AB  - Characterization of T-cell clones and identification of functional subsets of the
      helper T-cells with polarized cytokine production is based on testing of cytokine
      expression. Several methods have been developed that allow cytokine expression to
      be measured like ELISA, RT-PCR, ELISPOT, ISH and flowcytometry. Among all these
      methods, monitoring of cytokine production using flowcytometric analysis has its
      own advantages and disadvantages. Multi-parametric characterization of cytokine
      production on single cell basis, without long-term culture and cloning along with
      high throughput of samples is main feature attached to flowcytometric analysis.
      The interpretation may be difficult at times due to change in the phenotype of
      the cells. Cells with similar surface phenotype but synthesizing different
      cytokines and having different functional characteristics can be analyzed with
      this technique.

PMID- 12815289
TI  - Cell array coupled with laser scanning cytometry allows easy analysis of changes
      in cyclin expression during the cell cycle. An application of cell array system.
AB  - To assess the potential of cell array technology, a cell array slide with 50
      spots was designed specifically for automated analysis of changes in expression
      of cyclins A and B1 during the cell cycle at the cellular level. Cells harvested
      every 1 hour from 0 through 23 hours after synchronization by mitotic selection
      were spotted in duplicate on a glass slide. Each slide contained 48 spots
      representing 24 different cell cycle phases, and the remaining two spots were
      peripheral blood lymphocytes, which were included as negative control. This cell
      array provided temporal and spatial information related to changes in cyclin
      expression during the cell cycle in a single experiment. The present study
      indicates that expression analysis by cell array is novel approach for cell cycle
      studies. Furthermore, sophisticated multiplexed cell array technology has great
      potential for analyses of expression of specific genes during diverse cellular
      events at the cellular level.

PMID- 12815290
TI  - Flow cytometry and its application in small animal oncology.
AB  - Flow cytometry measures multiple characteristics of single cells. The use of flow
      cytometry in the veterinary clinical laboratory has increased considerably during
      the past decade. The most common applications of flow cytometry in small animal
      oncology are measurement of DNA content in tumours and immunophenotyping of
      haematopoietic malignancies. DNA ploidy and S-phase rate of various tumours in
      dogs have been found to be independent predictor of patient outcome. In dogs with
      lymphomas immunophenotyping is recommended as a part of the patient work-up. Flow
      cytometry has shown to be a suitable method for immunophenotyping of canine
      lymphomas. However, it has not become a routine technique in small animal
      oncology yet. This report reviews the applications of flow cytometry in small
      animal oncology. Besides basic principles and technical aspects, the clinical
      relevance of DNA-analysis and immunophenotyping are discussed.

PMID- 12815291
TI  - Flow cytometric monitoring of drug resistance in human tumor cells.
AB  - Recent studies have identified a family of glycoproteins which modulate cellular
      transport of antibiotics, alkaloids and drugs used in cancer chemotherapy. By
      facilitating efflux of drugs from the intracellular domain, these proteins reduce
      cytotoxicity and thus confer drug resistance. With the availability of antibodies
      raised against these phenotypic markers of drug resistance, immunohistochemistry
      and flow cytometry has been used to study their distribution and expression in
      normal and tumor cells. As some of the drugs used in cancer chemotherapy and
      other dyes which are substrates for this efflux pump are fluorescent, laser flow
      cytometry can be used for rapid quantitation of cellular retention, efflux and
      heterogeneity in drug transport of a tumor cell population. This method can also
      be used to screen drugs which may block efflux of a chemotherapeutic drug and
      thus increase chemosensitivity of a drug resistant tumor. In the present report
      flow cytometric methods for the study of drug transport and its modulation in
      tumor cells are discussed.

PMID- 12815292
TI  - Androgen receptor expression in archival human breast tumors.
AB  - Hormone receptors play a major role in growth and hormonal therapy of breast and
      prostate tumors. Quantitative results from the ligand binding assays cannot
      determine heterogeneity in receptor expression nor can they discriminate between
      expression of the stromal and the tumor cells. Availability of antibodies to
      hormone receptors has led to the development of immunohistochemistry as a
      standard method for monitoring of hormone receptor expression under a microscope.
      However, this method is based on examination of a small number of cells. Laser
      flow cytometry has been extensively used for monitoring of receptor expression in
      human liquid tumors. As most of the hormone receptor expression is nuclear, we
      have developed methods for flow cytometric analysis of receptor expression in
      nuclei isolated from enzyme treated paraffin sections. The present report based
      on gated analysis of androgen receptor expression in nuclei isolated from
      archival formalin fixed/paraffin embedded breast tumors shows that receptor
      expression in aneuploid sub-populations is greater than that of the diploid
      cells.

PMID- 12815293
TI  - Membrane oxidative damage and apoptosis in cervical carcinoma cells of patients
      after radiation therapy.
AB  - This article describes evaluation of plasma membrane fluidity and intracellular
      SOD with relation to apoptotic death of cervical carcinoma cells after radiation
      therapy. Cells from biopsies of cancer patients (stage IIIB) prior to and 24 h
      after radiation dose of 2 Gy were examined. Plasma membrane fluidity, measured by
      fluorescence polarization of DPH incorporated into lipid bilayer and superoxide
      dismutase (SOD) activity, determined by epinephrine method, showed significant
      decrease but per cent apoptotic cells, as determined by annexin-V and TUNEL
      methods, were found increased by two folds after radiotherapy. It is suggested
      that decrease in DPH polarization in membrane, reduction in SOD activity and
      increased apoptosis in cervical cells of cancer patients treated with radiation
      may be consequent to oxidative damage induced by reactive oxygen species (ROS),
      which may have implications in developing predictive protocol in cancer
      radiotherapy.

PMID- 12815294
TI  - Nitric oxide mediated modulation of free radical generation response in the rat
      polymorphonuclear leukocytes: a flowcytometric study.
AB  - Nitric oxide (NO) synthesis and free radical generation from polymorphonuclear
      leukocytes (PMNs) play an important role in several pathological conditions. It
      is therefore important to understand the regulatory mechanisms of free radical
      generation from PMNs. Flowcytometry can be used to assess generation of reactive
      oxygen and nitrogen species from PMNs by using fluorescent probes. In the present
      study regulation of NO synthesis in the control and lipopolysaccharide (LPS)
      treated rat PMNs has been investigated. Free radical generation was assessed by
      flow cytometry using a dye, 2'7'-dichlorodihydrofluorescein diacetate (DCFDA),
      dihydrorhodamine-123 (DHR) and 4,5-diaminofluorescein diacetate (DAF). Superoxide
      dismutase (SOD), and catalase significantly attenuated the arachidonic acid (AA,
      1 x 10(-6) M) induced free radical generation, while 4-aminobenzoicacid hydrazide
      (ABH), myeloperoxidase (MPO) inhibitor had no significant effect. Intracellular
      and extracellular calcium levels also modulated FR generation. AA induced free
      radical generation from PMNs was also enhanced significantly after LPS treatment.
      NO synthase (NOS) inhibitors, aminoguanidine (AG) and 7-nitroindazole (NI)
      inhibited arachidonic acid induced free radical generation from LPS treated PMNs,
      while in control PMNs NOS inhibition had no effect. Augmentation of free radical
      generation from rat PMNs following LPS treatment seems to be regulated by NO.

PMID- 12815295
TI  - Flowcytometric detection of PNH defect and response to therapy in aplastic anemia
      patients.

PMID- 12815296
TI  - Host-pathogen interactions: leukocyte phagocytosis and associated sequelae.
AB  - Polymorphonuclear leukocytes (PMNs) are a critical component of the human innate
      immune response and are the first line of defense against invading
      microorganisms. Phagocytosis of invading microbes induces production of reactive
      oxygen species (ROS) by PMNs, which facilitates bactericidal activity. In
      addition to eliminating microorganisms, phagocytosis also accelerates PMN
      apoptosis, a process critical for resolution of inflammation. Inasmuch as
      leukocyte phagocytosis and ROS production are key components of the innate immune
      response, we developed flow cytometric methods to evaluate these processes in
      human PMNs. In contrast to traditional microscopy-based analyses, the methods
      described herein provide objective and high throughput measures of host cell
      pathogen interactions. Importantly, they can be adapted for use with a number of
      fluorometric probes, and bacterium and host cell of choice, and each is based
      upon a common phagocytosis assay system. We also describe methods to measure
      phagocytosis-induced PMN apoptosis with this assay system. These methods entail
      detecting surface-exposed phosphatidylserine (early apoptosis), and measuring PMN
      chromatin condensation and DNA fragmentation (late apoptosis). Taken together,
      these assays provide rapid and accurate assessment of critical PMN processes.

PMID- 12815297
TI  - Flow cytometric techniques for the detection of microorganisms.
AB  - Flow cytometry (FCM) is a technique, which allows one to analyse cells rapidly
      and individually, and permits the quantitative analysis of distributions of a
      property or properties in a population. It therefore offers many advantages over
      conventional measurements for the analysis of biological cells. Historically the
      technique has been widely applied for the study of mammalian cells, but its use
      in microbiology has been more limited; this is mainly a consequence of the
      smaller size of microbes, which results in the smaller optical signals that can
      be obtained from them. Developments in light sources and optics, together with
      brighter, spectrally-diverse dyes have reduced this barrier over recent years and
      the flow cytometer is now an essential tool in many microbiological research
      establishments. FCM has an increasing role to play in the detection of microbes
      in both industrial and clinical settings. Environmental monitoring to prevent
      outbreaks of human diseases such as cryptosporidiosis and Legionnaires' disease
      and to detect acts of biowarfare or bioterrorism are all amenable to flow
      cytometric study. This review seeks to highlight the role of the flow cytometer
      in the detection of microbial cells.

PMID- 12815298
TI  - A flow cytometric approach to assess phytoplankton respiration.
AB  - Microbial respiration in the ocean is considered as the major process
      representative of the organic matter biological oxidation. The corresponding
      metabolic CO2 production was estimated to be about 22 Pg C y(-1). However, the in
      situ respiration rate is generally too low (by several orders of magnitude) to be
      accessible to the available direct measurement methods. Some fluorescent probes,
      such as DiOC6(3) (Molecular Probes, USA) have been shown to be very sensitive to
      changes in the proton electrochemical potential difference (DeltamuH+),
      characterising mitochondrial and plasmic membranes bearing the cell respiratory
      system in eukaryotic and prokaryotic cells respectively. In mitochondria,
      DeltamuH+ is linked to the flux of oxygen uptake by a linear relationship. To our
      knowledge, no such relationship has been established in the case of whole marine
      cells. In the present work, we addressed the dark respiration rate of the
      Chlorophyceae Dunaliella tertiolecta (Butcher) in axenic cultures, both directly
      by using a highly sensitive oxygraph (Oroboros) and by staining cells with
      DiOC6(3). We found and standardized a linear relationship between oxygen uptake
      by D. tertiolecta and its green fluorescence induced by DiOC6(3), enabling the
      determination by flow cytometry of the respiration rate of D. tertiolecta.

PMID- 12815299
TI  - Cellular and serological markers of disease activity in Indian patients with
      HIV/AIDS.
AB  - There has been an exponential rise of HIV positive patients as observed at the
      surveillance center of Nehru Hospital. Most patients are poor and cannot afford
      repeated viral load assays. Therefore, there is a need to identify cost effective
      and reliable surrogate markers of disease activity. In the present study absolute
      number of CD4 cells, beta2 micro-globulin, circulating nucleosomes were studied
      in 30 patients of AIDS, 30 seropositives and 30 healthy controls. In addition
      viral load, P-24 assay, and TNFR-II assays were done in seropositive and AIDS
      patients. The mean CD4 cells in patients with AIDS were 69.66 +/- 68.25 mm3 while
      in seropositives values was 370 +/- 201.29 mm3. The mean CD4 cells in healthy
      controls were however 690 +/- 198 mm3. The differences in all the groups were
      highly significant (p<0.001). The mean CD4 values in Indians are significantly
      lower than reported from the west. The lower number of CD4 cells in healthy
      population is interpreted to be due to immune activation. The CD8 cell number in
      controls was 650 +/- 207 mm3 this figure is also higher than that observed in the
      west. P-24 assay failed to delineate between seropositives and patients with
      AIDS. Although, beta2 microglobulin levels were significantly higher in AIDS than
      in seropositives and higher in seropositives than in controls yet with the best
      possible cut off, it had a sensitivity of only 70% in delineating the two
      conditions. The correlation between CD4 cells and viral load was more significant
      when the CD4 cells were below 200 mm3. Five out of 30 patients with a CD4 of 300
      600 mm3 had a viral load of over 1 x 10(5) cop/ml. The difference in TNF R-II
      levels between seropositives and AIDS was however more impressive. With a cut off
      of 550 pg/ml it had a sensitivity of 95% in delineating HIV from AIDS. It is
      concluded that a combination of absolute number of CD4 cells and TNF R-II assay
      along with clinical evaluation may be used to monitor therapy in resource poor
      countries where frequent viral load assay is unaffordable.

PMID- 12815300
TI  - Bundle branch block and cardiac resynchronization therapy: do we need to look
      further before we leap?

PMID- 12815301
TI  - Effect of 60 minutes of rapid atrial pacing on atrial action potential duration
      in the in-situ canine heart.
AB  - Right atrial monophasic action potentials were recorded before and after 60
      minutes of rapid atrial pacing (pacing cycle length (CL); 127 +/- 10 ms) in 12
      closed-chest dogs. The right atrial (RA) monophasic action potential (MAP)
      duration at 90% repolarization (RAMAPD) was measured at CLs of 400 ms and 250 ms.
      CL-dependent changes in RAMAPD (CL 400 ms - 250 ms) before and after rapid atrial
      pacing were 24 +/- 1 ms and 16 +/- 5 ms, respectively (p < 0.02). RAMAP was
      recorded at each atrial pacing CL starting at 240 ms decreasing by 10-ms
      increments. RAMAPD alternans was observed in 10 of 12 dogs at a CL of 163 +/- 17
      ms before and in 10 of 12 dogs at s CL of 198 +/- 29 ms (p < 0.01) after rapid
      atrial pacing. Sustained atrial fibrillation (AF) (>5 minutes) was induced in 1
      of 12 dogs at a pacing CL of 130 ms before rapid atrial pacing and in 4 of 12
      dogs at a pacing CL of 135 +/- 17 ms after rapid atrial pacing. Onset of AF was
      always preceded by the RAMAPD alternans. Sixty minutes of rapid atrial pacing
      leads to diminution of rate adaptation of atrial action potential duration (APD)
      and appearance of APD alternans of greater magnitude at longer CL, both of which
      may contribute to the initiation and perpetuation of AF during its early phase.

PMID- 12815302
TI  - Electrophysiologic effects of endothelin receptor-A blockade in patients with
      coronary artery disease.
AB  - Selective endothelin receptor-A antagonists are a promising new treatment in
      patients with heart failure and/or pulmonary hypertension. Animal studies have
      suggested that these agents may have additional cardiac electrophysiologic
      actions, however, no data exist in man. We examined the effects of acute
      endothelin receptor-A blockade on the sinus node, the atrioventricular node and
      on the ventricular myocardium, in patients with single-vessel coronary artery
      disease and preserved left ventricular function. The selective endothelin
      receptor-A antagonist BQ-123 was administered by the intracoronary route, in
      order to achieve maximum local cardiac effects. After endothelin receptor-A
      blockade, QT interval increased from 373 +/- 30 msec (mean +/- SD) to 395 +/- 20
      msec (p < 0.01) and QTc interval increased from 394 +/- 36 msec to 421 +/- 28
      msec (p < 0.01). QT-dispersion, calculated from 12-lead ECG, decreased from 40 +/
      18 msec to 24 +/- 8 msec (p < 0.01) and QTc-dispersion decreased from 44 +/- 20
      msec to 26 +/- 9 msec (p < 0.05). These changes were evident only after infusion
      in the left, but not in the right coronary artery. No effect was found on the
      sinus node, the atrioventricular node, or the ventricular effective refractory
      periods. We conclude that selective endothelin receptor A blockade lengthens
      ventricular repolarization and decreases its inhomogeneity. Further studies are
      needed to evaluate possible antiarrhythmic actions of this class of agent.

PMID- 12815303
TI  - Ablation of typical atrial flutter using a three-dimensional ultrasound mapping
      system.
AB  - AIMS: The aim of the study was to test the feasibility of the new Realtime
      Position Management mapping system for ablation of typical atrial flutter.
      METHODS AND RESULTS: The ultrasound multi-transducer catheters of the RPM Mapping
      System are placed in the coronary sinus and at the right ventricular apex.
      Position and movement of the ablation catheter can be depicted on the monitor at
      any time. Several guiding marks are set in the right atria and thus, define the
      subsequent lesion lines. A total of 15 patients were treated. In 13 patients
      complete bi-directional block was established after the ablation. In two patients
      only significant conduction delay was measured after the end of the procedure. A
      total of 10.2 +/- 6.3 cooled RF-applications were needed to reach the end-point
      of the procedure. The total energy was 18.76 +/- 13.23 J. The fluoroscopy time
      for ablation was 22.2 +/- 8.34 min. During a mean follow-up of 8.4 +/- 3.2 months
      no recurrence of atrial flutter occurred. One patient developed atypical flutter
      and another patient had atrial fibrillation. Both patients were treated with
      antiarrhythmic drugs. There was one ablation related complication, a pericardial
      effusion. CONCLUSION: The Realtime Position Management system is easy to manage
      and control. The precision of anatomical linear lesions is improved and
      fluoroscopic exposure time considerably reduced after learning curve.

PMID- 12815304
TI  - Change in distant atrial activation patterns during circumferential pacemapping
      of pulmonic vein ostium: implications for localizing triggers for atrial
      fibrillation.
AB  - INTRODUCTION: Unique intracardiac activation patterns recorded from multipolar
      catheters in the coronary sinus (CS) and posteromedial right atrium (RA) when
      pacing from ostium (os) of each pulmonic vein (PV) can serve as template for
      determining PV of origin of atrial premature complexes. Development of an
      accurate template requires knowledge of variations in activation pattern during
      pacing from different aspects of same PV. METHODS: In 25 patients undergoing
      catheter ablation for AF, a decapolar Lasso mapping catheter was placed at PV os
      of interest and multipolar catheters were placed in CS and RA-medial to crista
      terminalis (CT). For each PV, pacing was performed from Lasso catheter poles 1
      through 10. For each bipole paced, activation sequence in CS (proximal to distal
      & vice-versa) was assessed, activation time (pacing stimulus to earliest
      electrogram recorded in catheters in CS/along CT) was measured and difference (CS
      - CT time) was determined. Significant interpolar variation was defined as the
      difference between the shortest and longest CS - CT activation time of >/=25 msec
      when pacing from different bipoles of same PV. RESULTS: In 59 PVs [19 right
      superior (RS), 20 left superior (LS), 8 right inferior (RI) and 12 left inferior
      (LI)], 259 bipoles were paced (median of 4 bipoles/PV). During circumferential PV
      pacing activation sequence in CS catheter was distal to proximal in 84.4% left
      sided PVs (LSPV and LIPV) and proximal to distal in 92.6% right-sided PVs (RSPV
      and RIPV) with no change in activation sequence observed during pacing from
      different bipoles in same PV. Significant interpolar variation was observed with
      circumferential pacing in 1 of 19 RSPV (5.3%), 2 of 20 LSPV (10%), 1 of 12 LIPV
      (8.3%) and none of RIPV. CONCLUSION: Unique intracardiac activation patterns
      during ostial pacing from individual PV are not influenced by circumferential
      location of pacing site.

PMID- 12815305
TI  - Bezold-Jarisch-like reflex during Brockenbrough's procedure for radiofrequency
      catheter ablation of focal left atrial fibrillation: report of two cases.
AB  - Brockenbrough's puncture technique has been widely conducted in the
      electrophysiologic laboratory. We report here two cases exhibiting a rare
      complication of this procedure, which arose during the conduct of catheter
      ablation using radiofrequency energy delivered to the pulmonary vein for the
      treatment of focal left atrial fibrillation. These cases exhibited marked sinus
      bradycardia and profound hypotension, suggestive of a Bezold-Jarisch-like reflex,
      observed immediately after Brockenbrough's procedure but before radiofrequency
      application. ST elevation in the inferior leads was also observed in spite of
      normal coronary angiograms. This unanticipated transient complication was treated
      by intravenous administration of atropine, which had no influence on the ablation
      procedure or prognosis. This is speculated to be attributable to the elevation of
      vagal tone caused by the mechanical effects of transseptal puncture on the
      interatrial vagal network.

PMID- 12815306
TI  - Reentrant atrial tachycardia originating from the superior vena cava.
AB  - A 52-years old man with a previous pericardiotomy for idiopathic constrictive
      pericarditis underwent catheter ablation for drug-resistant atrial tachycardia
      (AT). The mechanism of the AT was considered as reentry because of resetting
      response and the entrainment phenomenon during AT. We introduced a 64-electrode
      basket catheter into the superior vena cava (SVC) during AT to obtain precise
      mapping. A fractionated potential preceding local atrial electrogram was recorded
      in the SVC. The earliest activation site of the potential was located at the
      anterior aspect of the SVC, 2 cm above the SVC-right atrium junction determined
      fluoroscopically. The fractionated potential at this site preceded the onset of
      the P wave by 115 msec. Radiofrequency catheter ablation at this site eliminated
      the tachycardia. At 6 months follow-up, the patient is free of AT. Reentrant AT
      involving the SVC is a candidate of RF ablation. Multielectrode basket catheter
      is useful for a detailed mapping of the SVC.

PMID- 12815307
TI  - Feasibility of atrial sensing via a free-floating single-pass defibrillation lead
      for dual-chamber defibrillators.
AB  - BACKGROUND: Detection and misclassification of rapidly conducted atrial
      fibrillation (AF) and marked sinus tachycardia by implantable cardioverter
      defibrillators (ICD) can result in the delivery of inappropriate therapies.
      Continuous atrial sensing may improve the differentiation between
      supraventricular and ventricular tachycardia. The present approach is to implant
      a separate atrial pacing lead connected to a dual-chamber defibrillator. We
      hypothesized that a free-floating single-pass defibrillation lead reliably senses
      the atrial electrical activity. The aim of the study was to assess during
      implantation the efficacy of a custom-built free-floating single-pass
      defibrillation lead and to record sinus rhythm (SR), induced AF, and atrial
      flutter (Afl). METHODS: The free-floating single-pass defibrillation lead
      (Biotronik, Berlin, Germany) had an atrial bipole with 10 mm spacing and a
      distance between the atrial bipole and the electrode tip of 13.5, 15 or 17-cm.
      The lead was temporarily implanted in 15 patients during an ICD implantation.
      Fifteen seconds recordings were made during SR and after the induction of AF and
      Afl as well as during induced ventricular fibrillation. The amplitude and the
      time that the amplitude was less than 0.3 mV were assessed. RESULTS: The
      amplitude during SR (2.1 +/- 1.4 mV) was significantly higher compared with the
      amplitudes for Afl (1.3 +/- 0.5 mV; p < 0.02) and AF (0.7 +/- 0.5 mV; p < 0.001).
      Low amplitudes were not observed during SR and rarely during Afl (1.6 +/- 3.1%),
      but they were observed 19.9 +/- 15.9% of the time during AF (p < 0.05). The
      correlation coefficients between SR and AF amplitudes were r = 0.25, between SR
      and Afl amplitudes r = 0.31, and between AF and Afl amplitudes r = 0.41. During
      the ventricular fibrillation conversion test 9 patients were in continuous SR.
      The P-wave amplitude before the induction of ventricular fibrillation was 2.1 +/-
      1.4 mV. The signal during ventricular fibrillation decreased to 1.1 +/- 0.7 mV
      and increased immediately after the termination of ventricular fibrillation to
      1.6 +/- 0.8 mV. CONCLUSIONS: The recorded unfiltered signals indicate that SR as
      well as AF and Afl can immediately be detected after the implantation of the new
      free-floating single-pass defibrillation lead. High signal amplitude during SR
      did not predict high amplitude during AF or Afl. During induced ventricular
      fibrillation the P-wave amplitude decreased intermittently.

PMID- 12815308
TI  - Is inappropriate implantable defibrillator shock therapy predictable?
AB  - OBJECTIVE: To identify implantable cardioverter defibrillator (ICD) patients who
      are at risk of receiving inappropriate shock. BACKGROUND: Inappropriate ICD
      shock, usually from atrial fibrillation (AF) or sinus tachycardia (ST), is a
      common problem. We hypothesized that clinical variables would predict which
      patients with single chamber ICDs would be more likely to receive inappropriate
      therapy and be candidates for more accurate discriminators such as those
      available in dual chamber ICDs. METHODS: The ICD registry at St. Michael's
      Hospital has it's clinical information and demographic data updated after each
      clinic visit. Inappropriate shock was considered as the outcome variable.
      Possible predictors considered were age, gender, ejection fraction, NYHA class,
      prior CABG and prior history of AF. Univariate predictors were identified using t
      test for continuous variables and Chi-square test for categorical variables.
      Multivariate predictors were identified using stepwise logistic regression
      analyses. RESULTS: Of 299 patients, 261 had complete data for analysis. In this
      population 78% were male, mean age was 60 +/- 13 years, mean ejection fraction
      was 37 +/- 15% and mean follow up was 53 +/- 36 months. One hundred and sixteen
      of the 261 patients (44%) received one or more inappropriate therapies (73%
      within 2 years of receiving their device), and 140 (51%) received one or more
      appropriate therapies. Significant predictors of inappropriate therapy by
      multivariate model were prior AF (OR 2.6, 95% CI 1.5-4.5) and NYHA class 1 vs.
      classes 2-4 (OR 2.2, 95% CI 1.2-3.7). CONCLUSION: Clinical characteristics of ICD
      patients can predict those at risk for inappropriate shock and should be
      considered for interventions to decrease such shocks.

PMID- 12815309
TI  - Prospective randomized comparison of 65%/65% versus 42%/42% tilt biphasic
      waveform on defibrillation thresholds in humans.
AB  - BACKGROUND: The waveform tilt of biphasic shocks yielding the lowest
      defibrillation threshold (DFT) is not well defined. Some evidence indicates that
      tilts less than 65% may improve DFTs. METHODS: In 57 patients undergoing ICD
      implantation, DFTs were determined with truncated exponential biphasic waveform
      tilts at 65%/65% and at 42%/42%. An external defibrillator with custom software
      was used for testing. The effective capacitance of the defibrillator was 132
      microF for both waveforms. DFTs were determined using a binary search method
      starting with 12 Joules (J). Patients were randomly assigned to initial testing
      with either one of the two tilts. Thirty patients (Group 1) were tested with a
      two electrode (active can to RV coil, or SVC coil to RV coil) and 27 patients
      (Group 2) were tested with a three electrode system (subcutaneous patch or active
      can + SVC coil to RV coil). RESULTS: Groups 1 and 2 did not differ in age,
      ejection fraction or antiarrhythmic medications. Group 1 delivered energy DFTs
      were 10.1 +/- 5.5 J with the 65%/65% tilt and 10.1 +/- 5.9 J for the 42%/42% tilt
      (p = 0.92). In group 2 the average DFT for the 65%/65% tilt was 8.4 +/- 5.7 J and
      for the 42%/42% tilt was 8.1 +/- 5.3 J (p = 0.70). There were no significant
      differences in DFTs for either group. The system impedance for Group 1 was 64 +/-
      12 ohms and for Group 2 was 39 +/- 6 ohms (p < 0.0001). CONCLUSIONS: We found no
      differences in DFTs between 65%/65% tilt and 42%/42% tilt using either 2- or 3
      electrode defibrillation systems. Further research is needed to optimize
      waveforms in order to minimize DFTs, which will result in smaller ICDs and/or
      greater safety margins for defibrillation.

PMID- 12815311
TI  - Retrovirally mediated overexpression of peroxiredoxin VI increases the survival
      of WI-38 human diploid fibroblasts exposed to cytotoxic doses of tert
      butylhydroperoxide and UVB.
AB  - In this work, stable overexpression of peroxiredoxin VI was generated in WI-38
      human diploid fibroblasts using a retrovirus-mediated transfection system.
      Estimation of cell survival showed that peroxiredoxin VI provides a significant
      protection against tert-butylhydroperoxide- or UVB-caused cytotoxicity. No
      protection was found against ethanol- or H(2)O(2)-caused cytotoxicity. These
      effects are correlated with the known functions of Prx VI.

PMID- 12815312
TI  - Melatonin-induced reduction in age-related accumulation of oxidative damage in
      mice.
AB  - The ever-increasing understanding of oxygen radical-linked diseases, including
      the biological process of aging, has stimulated general interest in modulating
      these biological events. Melatonin has been reported to have antioxidant
      properties in addition to its known hormonal activities. However, reports on low
      level chronic administration with its anti-aging influence are scanty. Hence, the
      present study was aimed to investigate the influence of low-dose chronic
      administration (0.10 mg/kg body weight/day for 3 months) of melatonin against age
      induced oxidative stress in mice tissues, namely brain, liver, spleen and kidney.
      Sixteen-month-old mice were supplemented with melatonin (0.10 mg/kg body
      weight/day) for three months and then autopsied (at the age of 19 months) for the
      biochemical estimation of lipid peroxidation, reduced glutathione (GSH),
      glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px) and serum
      phosphatase activity. Results indicate that age-induced augmentation (compared to
      6-8-week-old mice) in the level of lipid peroxidation, GSSG and acid phosphatase
      is significantly (P < 0.001) ameliorated in melatonin-treated mice. Age-induced
      decline in the level of GSH, GSH-Px and alkaline phosphatase activity is
      inhibited significantly by the long-term administration of melatonin. The
      findings indicate that low-dose chronic administration of melatonin acts as a
      free radical scavenger and anti-aging agent.

PMID- 12815313
TI  - Short-term caloric restriction and regulatory proteins of apoptosis in heart,
      skeletal muscle and kidney of Fischer 344 rats.
AB  - Long-term caloric restriction reduces oxidative stress, increases mean and
      maximum lifespan in rodents and tends to enhance apoptosis, particularly in the
      liver. We investigated the effect of short-term (2 months) caloric restriction
      (40% reduction) in 6-month-old male Fischer 344 rats on various indicators of
      apoptosis (caspase-3, -7, -12, the inhibitor of apoptosis protein XIAP and
      cytoplasmic histone-associated DNA fragments) in the post-mitotic heart and
      gastrocnemius muscle, and the kidney that contains mitotic cells. Short-term
      caloric restriction significantly reduced body mass (30%), gastrocnemius muscle
      mass (22%), heart mass (25%) and kidney mass (32%) compared to ad libitum
      controls. The levels of procaspase-3 in gastrocnemius muscle and caspase-3 in
      kidney were significantly lower in the caloric restricted than in the ad libitum
      fed group. While caloric restriction did not alter DNA fragmentation levels
      (indicative of apoptosis), differences did exist amongst tissues with
      significantly elevated levels of fragmentation in the kidney compared to the
      heart and gastrocnemius muscle and significantly higher levels in the heart
      compared to gastrocnemius muscle. No differences were observed between groups in
      the levels of procaspase-7 or -12 or in XIAP (an endogenous inhibitor of
      apoptosis, particularly of caspase-3 and -7) in any tissue. The active forms of
      caspase-7 and -12 were present only in the kidney. These findings suggest that
      while the rate of apoptosis was higher in the kidney, which contains mitotic
      cells, compared to the post-mitotic heart and gastrocnemius muscle, short-term
      caloric restriction did not enhance the apoptosis rate in any tissue measured.

PMID- 12815314
TI  - Lifespan extension of Drosophila melanogaster through hormesis by repeated mild
      heat stress.
AB  - We assessed the impact of repeated episodes of a mild heat stress on lifespan,
      fecundity, heat stress resistance and Hsp70 expression in Drosophila
      melanogaster. There was a significant increase in lifespan of females repeatedly
      exposed to a mild heat stress when measured in both a pair and a group situation.
      There was no effect on fecundity when the flies were first exposed to the mild
      heat stress at an age later than 3 days old, but when it did occur on day 3,
      there was a significant effect on cumulative fecundity levels over 18 days. The
      negative fitness effect appears to be the result of a direct cessation or
      reduction of oviposition during the first bout of stress exposure, and is
      influenced by the age at which this first exposure occurs. The mild heat stress
      had no impact on egg viability. The mild heat stress exposures increased
      resistance to potentially lethal heat stress and levels of Hsp70 expression in
      heat-exposed flies were higher than those in controls.

PMID- 12815315
TI  - Efficient measurement of H2O2 resistance in Drosophila using an activity monitor.
AB  - We have established a method for the efficient measurement of oxidative stress
      resistance in Drosophila melanogaster, using a commercially available activity
      monitor. Conditions under which flies in glass tubes placed in the monitor can
      survive over one month at 25 degrees C were optimized. The active periods of
      flies were reduced by administration of H(2)O(2) into the media in a dose
      dependent manner. Although we used only eight flies per assay, far fewer
      individuals than in conventional methods, it was possible to detect the effects
      of H(2)O(2) at a statistically significant level. Increased levels of H(2)O(2)
      resistance were confirmed in transgenic flies overexpressing antioxidant enzymes,
      catalase or Cu/Zn superoxide dismutase. We applied the method to determine
      oxidative stress resistance in fly lines bearing insertions of a gene
      misexpression vector. H(2)O(2) resistance in these flies varied considerably
      depending on the insertion, and positively correlated with previously determined
      longevity. We identified one insertion that conferred a significantly higher
      level of resistance to H(2)O(2) compared to controls. Molecular analysis of the
      insertion revealed that a misexpressed transcript matched an expressed sequence
      tag, and suggested that its full-length product was overproduced upon GAL4
      activation. Our method should be applicable to the systematic screening for genes
      involved in the antioxidant mechanism in Drosophila.

PMID- 12815316
TI  - Immunosenescence and human longevity.
AB  - Humans are almost certainly the longest-living of all mammals. What explains
      their longevity? Are there evolutionary pressures favouring longer life and if so
      what are they? If longevity is a positively selected trait, are many or few genes
      responsible for this characteristic? It is proposed here that human longevity was
      selected for at the level of relatively few genes and that many of these are
      involved in regulating the immune system.

PMID- 12815317
TI  - The intra-individual diversity in senescence.
AB  - One of the most characteristic and widely observable features of senescence,
      usually ignored by scientific investigation, is a very variable, dapple
      distribution of its manifestations, seen within systems, organs, and tissues of
      the same individual. Different parts of an organ or tissue undergo senescence at
      different ages. The early aged foci may form only small solitary places in a
      tissue, an organ, a region, or an organism or in large parts of it. The
      proportion of early aged parts to later aged ones, as well as their localization,
      is predestined by individual genetic makeup, thus determining diversity in the
      course and forms of senile regression and the lifespan of organisms under
      consideration. It is a kind of biodiversity that is least known. To clear up what
      we can say about the nature of the phenomenon today, the features of this kind of
      human body diversity were interpreted using the data and conceptions of
      immunology, molecular biology and genetics. The results of the interpretation
      allow us to suppose that different parts of a human body usually have unequal
      genetic limits of life duration and their own programs of ageing; each of them
      has its own 'biological watch' which tells a different time. The genesis of this
      diversity can be explained by hybridization of persons with different genetic
      susceptibility to internal and/or environmental factors inducing senescence.

PMID- 12815318
TI  - Effects of anti-allergic drugs on intestinal mastocytosis and worm expulsion of
      rats infected with Neodiplostomum seoulense.
AB  - The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion
      of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral
      infection with 500 metacercariae. The drugs used were hydroxyzine (a histamine
      receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell
      suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but
      untreated controls, and uninfected controls, were prepared. Worm recovery rate
      and intestinal mastocytosis were measured on weeks 1, 2, 3, 5, and 7 post
      infection. Compared with the infected controls, worm expulsion was significantly
      (P < 0.05) delayed in hydroxyzine- and cimetidine-treated rats, despite
      mastocytosis being equally marked in the duodenum of all three groups. In the
      cyclosporin-A- and prednisolone-treated groups, mastocytosis was suppressed, but
      worm expulsion was only slightly delayed, without statistical significance. Our
      results suggest that binding of histamine to its receptors on intestinal smooth
      muscles is more important in terms of the expulsion of N. seoulense from rats
      than the levels of histamine alone, or mastocytosis.

PMID- 12815320
TI  - A case of acute gastric anisakiasis provoking severe clinical problems by
      multiple infection.
AB  - Acute gastric anisakiasis with multiple anisakid larvae infection is reported. A
      68-year-old woman residing in Busan, Korea, had epigastric pain with severe
      vomiting about 5 hours after eating raw anchovies. Four nematode larvae
      penetrating the gastric mucosae in the great curvature of the middle body and
      fundus were found and removed during gastro-endoscopic examination. Another one
      thread-like moving larva was found in the great curvature of upper body on the
      following day. On the basis of their morphology, the worms were identified as the
      3rd stage larvae of Anisakis simplex. This case is acute gastric anisakiasis
      provoking severe clinical problems by the multiple infection and the greatest
      number of anisakid larvae found in a patient in Korea.

PMID- 12815319
TI  - Molecular cloning of ribosomal P protein in Toxoplasma gondii and the
      availability to detect antibody against recombinant protein in toxoplasmosis
      patients.
AB  - Among the panel of monoclonal antibodies (mAb) against Toxoplasma gondii, mAb of
      Tg621 (Tg621) clone blotted 38 kDa protein which localized in the cytoplasm of
      tachyzoites by immunofluorescence microscopy. The protein was not released into
      the parasitophorous vacuole during or after invasion. The cDNA fragment encoding
      the protein was obtained by screening a T. gondii cDNA expression library with
      Tg621. The full length cDNA sequence was completed with 5'-RACE as 1,592 bp,
      which contained open reading frame of 942 bp. The deduced amino acid sequence of
      Tg621 consisted of a polypeptide of 313 amino acids, with significant homology to
      ribosomal P proteins (RPP) of other organisms especially high to those of
      apicomplexan species. The expressed and purified TgRPP was assayed in western
      blot with the sera of toxoplasmosis patients and normal sera, which resulted in
      the 74.0% of positive reactions in toxoplasmosis patients whereas 8.3% in normal
      group. Therefore, the antibody formation against TgRPP in toxoplasmosis patients
      was regarded as specific for T. gondii infection and suggested a potential
      autoantibody.

PMID- 12815321
TI  - Identification of Acanthotrema felis (Digenea: Heterophyidae) metacercariae
      encysted in the brackish water fish Acanthogobius flavimanus.
AB  - The metacercariae of Acanthotrema felis Sohn et al., 2003 (Digenea:
      Heterophyidae) were discovered in a species of the brackish water fish,
      Acanthogobius flavimanus, in the Republic of Korea. They were experimentally fed
      to kittens, and adult flukes were harvested 7 days later. The adults were
      morphologically characterized by the presence of a bipartite seminal vesicle, the
      ventral sucker associated with a ventrogenital sac enclosing 3 sclerites (2 long
      and pointed, and 1 short and thumb-like), and an unarmed gonotyl. The adult
      flukes were identified as A. felis Sohn et al., 2003, and the brackish water fish
      A. flavimanus has been verified as one of its second intermediate hosts.

PMID- 12815322
TI  - Surface ultrastructure of the adult stage of Acanthotrema felis (Trematoda:
      Heterophyidae).
AB  - The surface ultrastructure of Acanthotrema felis (Trematoda: Heterophyidae)
      adults, recovered from a kitten experimentally infected with the metacercariae,
      was observed using a scanning electron microscope. The worm was leaf-like,
      ventrally concave and covered with scale-like multi-pointed tegumental spines.
      The spines on the anterior surface were short but broad, and had 10-12 pointed
      tips. The cytoplasmic processes protruded around the spines, like pockets for the
      spines. The ventrogenital opening was crescent, or kidney-shaped, and had
      protuberances with minute spines on its surrounding tegument. The spines on the
      posterior surface were long, but narrow, with 6-8 pointed tips. The cytoplasmic
      processes on this tegument were ridge-like, and elevated along the row of the
      spines. The surface ultrastructure of A. felis is generally similar to that of
      other heterophyid flukes, but some features are characteristic, and may be of
      taxonomic and bio-ecological significance.

PMID- 12815323
TI  - The intestinal parasite infection status of inhabitants in the Roxas city, The
      Philippines.
AB  - We carried out a small-scale survey to investigate the status of intestinal
      protozoa and helminthes infection of inhabitants in Roxas city, Mindoro, the
      Philippines. Total 301 stool samples were subjected to the formalin-ether
      concentration method for the detection of helminth ova and protozoan cysts. The
      overall positive rate was 64.5%, and that of male and female were 56.6% and
      72.5%, respectively. The highest infected helminth was Ascaris lumbricoudes
      (51.2%), followed by Trichuris trichiura (27.6%), hookworm (8.0%) and Enterobius
      vermicularis (0.3%). The protozoa infection status revealed that Entamoeba coli
      was the most frequent (15.0%). Iodoamoeba buetschlii and E. histolytica were
      found but few. The multiple infection more than two parasites was 29.6%, and
      double infection with A. lumbricoides and T. trichiura was most common. The
      intestinal helminth infections were highly prevalent in this area, according to
      this result, and we concluded that anthelminthic drugs should be given to
      inhabitants, especially to children of 1 to 15 years-old.

PMID- 12815325
TI  - Usefulness of 8 kDa protein of Fasciola hepatica in diagnosis of fascioliasis.
AB  - This study was designed to detect and evaluate an antigenicity of low molecular
      weight proteins of Fasciola hepatica in fascioliasis. Low molecular weight
      protein of F. hepatica was purified by ammonium sulfate precipitation and
      Sephacryl S-100 HR gel filtration. The protein obtained was estimated to be 8 kDa
      on 7.5-15% gradient sodium dodecyl sulfate gel electrophoresis. Immunoblotting
      studies showed that the 8 kDa protein reacted with human fascioliasis sera, but
      not other trematodiasis sera. This result suggests that the 8 kDa protein of F.
      hepatica is one of diagnostic antigens in human fascioliasis without cross
      reaction with other human trematodiasis.

PMID- 12815324
TI  - A human case of Echinostoma hortense (Trematoda: Echinostomatidae) infection
      diagnosed by gastroduodenal endoscopy in Korea.
AB  - A human Echinostoma hortense infection was diagnosed by gastroduodenoscopy. An 81
      year-old Korean male, living in Yeongcheon-shi, Gyeongsangbuk-do and with
      epigastric discomfort of several days duration, was subjected to upper
      gastrointestinal endoscopy. He was in the habit of eating fresh water fish. Two
      live worms were found in the duodenal bulb area and were removed using an
      endoscopic forceps. Based on their morphological characteristics, the worms were
      identified as E. hortense. The patient was treated with praziquantel 10 mg/kg as
      a single dose. The source of the infection in this case remains unclear, but the
      fresh water fish consumed, including the loach, may have been the source. This is
      the second case of E. hortense infection diagnosed by endoscopy in Korea.

PMID- 12815326
TI  - Molecular identification of Korean Trichinella isolates.
AB  - Muscle larvae of Trichinella isolates from two outbreaks in Korea were analyzed
      by a polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) and multiple-PCR. All of the muscle larvae showed a band similar to that of
      T. spiralis larvae of the reference strain. The two Korean Trichinella isolates
      (isolate code ISS623 and ISS1078) might be classifiable to Trichinella spiralis.

PMID- 12815327
TI  - Cloning of a pore-forming subunit of ATP-sensitive potassium channel from
      Clonorchis sinensis.
AB  - A complete cDNA sequence encoding a pore-forming subunit (Kir6.2) of ATP
      sensitive potassium channel in the adult worm, Clonorchis sinensis, termed
      CsKir6.2, was isolated from an adult cDNA library. The cDNA contained a single
      open-reading frame of 333 amino acids, which has a structural motif (a GFG-motif)
      of the putative pore-forming loop of the Kir6.2. Peculiarly, the CsKir6.2 shows a
      lack-sequence structure, which deleted 57 amino acids were deleted from its N
      terminus. The predicted amino acid sequence revealed a highly conserved sequence
      as other known other Kir6.2 subunits. The mRNA was weekly expressed in the adult
      worm.

PMID- 12815328
TI  - Comparison of carbohydrate moieties of sparganum proteins of the snake, mouse and
      those of adult worm.
AB  - The carbohydrate moieties of larval sparganum proteins in two different species,
      the snakes, Elaphe rufodorsata, the Balb/c mouse and those of the adult worm,
      Spirometra erinacei, were compared using five different lectins including GNA,
      SNA, MAA, PNA and DSA. The GNA positive 53 kDa molecule, which is excretory
      secretory protease in the sparganum from the snake showed a stage specific and
      developmental regulation. We also suggested that sparganum glycosylation may be
      involved in immune evasion and differentiation into an adult worm.

PMID- 12815330
TI  - Extracellular calcium-sensing receptors in the parathyroid gland, kidney, and
      other tissues.
AB  - PURPOSE OF REVIEW: The discovery of the extracellular calcium-sensing receptor,
      CasR has broadened our understanding of calcium homeostasis and led to the
      development of new pharmacological agents, calcimimetics, for treating
      hyperparathyroidism. In the present review, I discuss the function of CasR as
      well as provide evidence for the presence of additional calcium-sensing
      mechanisms in the skeleton and possibly other tissues. RECENT FINDINGS:
      Inactivating and activating mutations of the CasR respectively cause hereditary
      hyperparathyroidism, and demonstrate the predominant role of the CasR in
      controlling parathyroid gland function. Calcimimetics, which increase the
      sensitivity of CasR to extracellular calcium have been developed to treat
      secondary and primary hyperparathyroidism. In recent clinical trials in patients
      with end stage kidney disease, the calcimimetic cinacalcet suppressed parathyroid
      hormone to a greater degree than conventional therapy with vitamin D analogues
      without causing hypercalcemia or hyperphosphatemia. CasR receptor also has
      functions in other tissues, including regulation of renal calcium excretion and
      calcitonin secretion by thyroidal C-cells, but the presence of redundant sensing
      mechanisms for extracellular calcium in other tissues, including bone, confounds
      the assessment of the receptor's function at these sites. Mouse genetic
      approaches have so far failed to identify any essential, non-redundant role for
      the calcium-sensing receptor in regulating chondrogenesis or osteogenesis, and
      have failed to establish a function for the protein outside of the parathyroid
      gland, kidney, and thyroidal C-cells. Rather, there is evidence for other
      putative calcium sensing receptor-like mechanisms in osteoblasts that remain to
      be identified. SUMMARY: Sensing of extracellular calcium by CasR is important in
      regulating calcium homeostasis, but CasR may have vestigial function in various
      tissues where it is expressed in low abundance. The relative importance of CasR
      and the novel calcium-sensing mechanisms in mediating response to extracellular
      calcium in many of these tissues remain to be determined.

PMID- 12815331
TI  - Sensing phosphate across the kingdoms.
AB  - PURPOSE OF REVIEW: The present review summarizes recent findings that may help in
      understanding how the cell senses changes in serum phosphate. RECENT FINDINGS:
      The sensing of phosphate determines the organism's response to change in supply
      of this essential nutrient. Phosphate depletion or surfeit results in homeostatic
      responses that involve changes in transcription, transcript stability,
      transporter recruitment or breakdown, and cell replication. These responses are
      shared across the biological kingdoms, and lessons from unicellular organisms may
      be relevant to multicellular mammals. An understanding of nutrient sensing in
      general may help in determining how the cell senses changes in phosphate
      concentration. SUMMARY: Research has yielded important advances in unravelling
      phosphate sensing and the response to nutrient phosphate supply. However, the
      actual sensing event for phosphate and most other nutrients must still be
      defined. Lessons may be learned from those examples in which the sensing event is
      known, and these are summarized here.

PMID- 12815332
TI  - Involution of the parathyroid glands after renal transplantation.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the most recent
      development on the reversibility of secondary hyperparathyroidism after kidney
      transplantation. A successful kidney transplantation is expected to correct the
      abnormalities of mineral metabolism that during uremia lead to secondary
      hyperparathyroidism. Kidney transplanted patients might, however, still present
      persistent hyperparathyroidism and hypercalcemia. In order to improve the
      understanding of the fate of secondary hyperparathyroidism after kidney
      transplantation an experimental model on reversal of uremia by an experimental
      isogenic kidney transplantation was established. RECENT FINDINGS: In recent years
      clinical and experimental studies have suggested an important role of the calcium
      sensing receptor and vitamin D receptor in the parathyroid glands for the
      abnormal regulation of parathyroid hormone secretion and parathyroid cell
      proliferation in uremia. The expression of these receptors is diminished in the
      parathyroid glands of uremic patients with severe secondary hyperparathyroidism
      and in experimental models of uremic rats on a high phosphorus diet. Secondary
      hyperparathyroidism is reversed rapidly by reversal of uremia by an experimental
      kidney transplantation in the rat. Despite normalization of the circulating
      parathyroid hormone levels, diminished expression of parathyroid calcium sensing
      and vitamin D receptor messenger RNA persist. Implantation of several isogenic
      parathyroid glands into a single rat results in a transient, short lasting period
      of hypercalcemia followed by normalization of parathyroid hormone and plasma
      calcium levels, despite persistent increased parathyroid mass. SUMMARY: Advances
      are clearly being made in the understanding of the molecular mechanisms of
      disturbed parathyroid function in uremia. How the hyperplastic uremic parathyroid
      glands are regulated after reversal of uremia by kidney transplantation remains,
      however, to be elucidated.

PMID- 12815333
TI  - Calcium salts in the treatment of hyperphosphatemia in hemodialysis patients.
AB  - PURPOSE OF REVIEW: Hyperphosphatemia in patients with end-stage renal disease
      leads to secondary hyperparathyroidism and renal osteodystrophy, and is
      independently associated with mortality risk. How hyperphosphatemia increases
      mortality risk is unknown but it may promote cardiovascular calcification. It is
      recommended that dialysis patients be treated to maintain normal serum
      phosphorus. Although calcium-based phosphate binders are cost-effective, their
      long-term safety has been questioned because of their postulated role in
      progression of cardiovascular calcification. In this regard, sevelamer
      hydrochloride has been recommended as an alternative phosphate binder. In this
      review, we will examine these issues and provide rational guidelines for the use
      of calcium-based phosphate binders. RECENT FINDINGS: Results from the calcium
      acetate Renagel evaluation study indicate that calcium acetate is more effective
      than sevelamer in controlling serum phosphorus and calcium x phosphorus product
      in hemodialysis patients. However, in the Treat-to-Goal study dialysis patients
      treated with sevelamer had less progression of coronary and aortic calcification
      than patients treated with calcium-containing binders. The mechanism underlying
      the slower rate of progression of cardiovascular calcification in sevelamer
      treated patients remains uncertain but may relate to decreased calcium loading or
      to dramatic reductions in LDL cholesterol. SUMMARY: At present, evidence
      incriminating calcium-containing phosphate binders in the progression of
      cardiovascular calcification in end-stage renal disease remains largely
      circumstantial. As calcium acetate is more efficacious and cost-effective than
      sevelamer, it remains an accepted first-line drug. Treatment with sevelamer
      hydrochloride should be considered for patients with persistent hypercalcemia
      during calcium-based binder therapy despite appropriate adjustment of vitamin D
      therapy.

PMID- 12815334
TI  - Postmenopausal osteoporosis in the dialysis patient.
AB  - PURPOSE OF REVIEW: Osteoporosis is the most prevalent bone disorder in the
      general population, particularly in the middle and older age groups. Although
      more than half of the prevalent dialysis population is within these age groups,
      little concern has been given to the possible role of estrogen deficiency in the
      pathogenesis of bone disease in end-stage renal disease. The purpose of this
      review is to summarize the recent published evidence that supports a potential
      role of the postmenopausal state in the pathogenesis of bone disease in end-stage
      renal disease and their implications for treatment. RECENT FINDINGS: Recent
      studies have shown that although the risk factors for fracture in end-stage renal
      disease are similar to the general population, the incidence is three to fourfold
      higher. The high prevalence of older population, the frequently observed
      premature amenorrhea and early menopause in dialysis patients may play a role.
      Similarly, the proportion of end-stage renal disease women receiving hormone
      replacement therapy is at least three times lower than the general population.
      Recent evidence on the risk of hormone replacement therapy should caution about
      its use in end-stage renal disease patients. New evidence suggests that selective
      estrogen receptor modulators may increase bone mass without significant secondary
      effects. Other alternatives, such as the use of bisphosphonates, should be
      considered with caution due to the risk of excessive suppression of bone
      turnover, worsening or favoring the development of adynamic bone disease.
      SUMMARY: Osteoporosis should be recognized as an important entity that may modify
      the current conception of renal osteodystrophy in postmenopausal patients with
      end-stage renal disease. Further clinical studies are needed in order to propose
      strategies that may reduce the impact of postmenopausal osteoporosis in the
      dialysis population.

PMID- 12815335
TI  - Renal bone disease: a new conceptual framework for the interpretation of bone
      histomorphometry.
AB  - My purpose in this article is to restore the histologic appraisal of renal bone
      disease to the mainstream of bone and mineral metabolism from which it has been
      separated for many years. Historically, both the two major components were found
      in varying degrees in most patients, although one or other of them often
      predominated. For more than 15 years bone biopsy has been used almost exclusively
      to classify individual patients into hyperparathyroid, osteomalacic, mixed and
      adynamic categories according to rigid non-overlapping criteria, and remarkably
      few histologic data have been reported. All metabolic bone diseases result from
      disordered bone remodeling, the physiologic mechanism for replacing bone that has
      become too old to carry out its mechanical or metabolic functions. Bone
      remodeling is not directly concerned with the regulation of plasma calcium, which
      reflects the level of equilibration at quiescent bone surfaces between systemic
      and bone extracellular fluid set by parathyroid hormone. The separation of
      remodeling from homeostasis explains the concurrence of increased turnover and
      decreased plasma calcium in chronic renal failure; it is the homeostatic system,
      rather than the remodeling system, which is resistant to parathyroid hormone. The
      effect of mild hyperparathyroidism is a nonspecific increase in bone turnover, of
      which the best index is the bone formation rate measured by double tetracycline
      labeling expressed per unit of bone surface. Increased turnover is always
      accompanied by increased reversible mineral deficit. In prolonged
      hyperparathyroidism there is also accelerated irreversible bone loss manifested
      mainly as thinning of cortical bone, detectable in chronic renal failure before
      any symptoms, due to increased resorption depth on the endocortical surface. In
      severe hyperparathyroidism resorbed bone is replaced, not by a lesser quantity of
      normal bone, but by a mixture of vascular fibrous tissue and woven bone, referred
      to as osteitis fibrosa. In osteomalacia there is increased accumulation of
      osteoid, due not to increased turnover, but to prolongation of mineralization lag
      time, which in conjunction with increased thickness, surface and volume of
      osteoid is diagnostic. Converting histomorphometric data into category assignment
      discards most of the useful information, which can be retained by two-dimensional
      representation of severity. For the hyperparathyroid dimension, bone formation
      rate measured by double tetracycline labeling expressed per unit of bone surface
      is the most useful although not ideal. For the osteomalacic dimension a
      mineralization index was constructed that is unaffected by age or race. In
      patients with osteitis fibrosa, bone formation rate per unit of bone surface and
      mineralization index were inversely correlated. For the third dimension a
      structure/formation index was constructed which increases with age in healthy
      women and shows weak inverse correlation with bone formation rate. The
      structure/formation index is lower than normal in patients with osteitis fibrosa,
      and should be useful in the study of osteopenia in chronic renal failure. Bone
      formation rate is low in osteomalacia, but some patients have subnormal rates
      through quite a different mechanism. The frequency of this finding has been
      overestimated for several reasons: failure to exclude atypical osteomalacia
      (increased surface and volume but not thickness of osteoid), use of inappropriate
      reference values, and failure to measure the bone formation rate on endocortical
      and intracortical surfaces. In healthy women bone formation rate can be zero on
      the cancellous surface alone. Low bone formation rate is sometimes due to
      diabetes but most often is the expected response to subnormal parathyroid hormone
      secretion accompanying an excess of calcium, a situation recognized only recently
      because of improvement in parathyroid hormone assay methodology. Low cancellous
      bone formation rate should not increase fracture risk because turnover is much
      lower in the peripheral than in the central skeleton, and all reports of
      increased fracture risk are flawed or open to different interpretation. Low bone
      formation rate is associated with reduced skeletal buffering of calcium and
      increased soft tissue calcification. This is not a new disease needing its own
      treatment, however, but represents the final stage of skeletal adaptation to a
      surfeit of calcium. The concept of adynamic bone disease has been harmful by
      directing attention away from the most important consequence of over-treatment of
      hyperparathyroidism.

PMID- 12815337
TI  - DNA expression analysis: serial analysis of gene expression, microarrays and
      kidney disease.
AB  - PURPOSE OF REVIEW: Expression profiling using serial analysis of gene expression
      and microarray technologies allows global description of expressed genes present
      in biological systems. Although relatively new technologies, each having been
      developed in the mid-1990s, both have become established and widely used tools
      for identification of gene networks and gene function. RECENT FINDINGS: This
      review highlights DNA expression analyses published in 2002, emphasizing
      primarily serial analysis of gene expression and microarray technologies. We
      focus on the applicability of DNA expression analysis to renal disease,
      especially as some investigators have developed custom serial analysis of gene
      expression kidney libraries and kidney disease-specific 'designer chip'
      microarrays. Data analysis techniques and statistics are also discussed, since
      the challenge is generation of accurate messenger RNA profiles and interpretation
      of data in a manner that is both coherent and reproducible. SUMMARY: Because
      kidney disease pathophysiology is complex, expression analysis can identify
      candidate nephropathy pathogenesis genes and gene networks, which eventually
      could become targets for therapeutic intervention.

PMID- 12815338
TI  - Nucleic acid-based techniques for post-transcriptional regulation of molecular
      targets.
AB  - PURPOSE OF REVIEW: Messenger RNA, transfer RNA and ribosomal RNA were defined
      long ago as essential components for transmission of genetic code from DNA.
      However, there are many other, less commonly recognized RNAs, such as ribozymes
      and small interfering RNAs, which are distinguished by their ability to inhibit
      RNA function. This review describes the basic molecular concepts and potential
      therapeutic applications of RNA inhibition by a variety of molecules, including
      ribozymes, antisense oligonucleotides, aptamers and small interfering RNAs.
      RECENT FINDINGS: A tremendous amount of data has recently emerged about double
      stranded small interfering RNAs, which bind and degrade corresponding messenger
      RNAs by a process called RNA interference. Though native small interfering RNAs
      have been shown to be biologically relevant in animals and plants, synthetic
      types have rapidly become powerful tools for post-transcriptional inhibition of
      specific gene products to determine functional consequences in simple organisms
      and in-vitro model systems. More established means of RNA inhibition, such as
      with ribozyme and antisense strategies, continue to be viable options for in
      vitro experiments, and form the basis for many ongoing clinical trials. SUMMARY:
      Ribozymes, antisense oligonucleotides, aptamers and small interfering RNAs are
      potentially useful reagents for in-vitro investigation and for treatment of
      kidney and hypertension diseases.

PMID- 12815339
TI  - Proteomics.
AB  - PURPOSE OF REVIEW: Proteomics encompasses a group of technologies that attempt to
      separate, identify and characterize a global set of proteins. This review will
      highlight the technologies available, outline the capabilities, advantages and
      disadvantages of each and briefly describe applications in nephrology. RECENT
      FINDINGS: Proteomics provides information about abundance, location, chemical
      modification and protein-protein interactions that is not available from genomic
      technologies. Several proteomic approaches are now widely available. Liquid
      chromatography/mass spectrometry, two-dimensional gel electrophoresis, antibody
      arrays and protein chips (surface enhanced laser desorption ionization) provide
      opportunities to identify and compare an abundance of proteins as well as to
      determine posttranslational modifications, subcellular location and molecular
      interactions. Recent advances such as multidimensional chromatographic analysis
      and isotope coded affinity tags have expanded the usefulness of these approaches.
      SUMMARY: Proteomic technologies are improving and developing rapidly. These
      techniques will be valuable tools to develop markers for disease, identify and
      evaluate proteins as drug targets and understand renal physiology at the protein
      level.

PMID- 12815340
TI  - Structural biology: a high-tech tool for biomedical research.
AB  - PURPOSE OF REVIEW: Structural biology is one of the most informative disciplines
      available to biochemical research. It unites technologies that can reveal high
      resolution (often atomic) details of the inner workings of biochemical systems.
      These insights are crucial for an understanding of basic life processes, such as
      the reaction mechanism of a drug-converting enzyme, signal transduction from one
      protein to another, activation of a metabolic pathway by a gene effector, action
      modes of drugs, or the consequences of a mutation on the function of an enzyme.
      Structural biology is also vital for characterizing the molecular basis of many
      diseases and often provides a starting platform for the development of
      specifically tuned therapies, for example by designing drugs that bind to
      particular targets in order to affect their functionality. An overview of the
      main techniques as well as some selected case studies are presented. RECENT
      FINDINGS: Recent advances in the three major structure determination techniques
      (X-ray crystallography, nuclear magnetic resonance spectroscopy, and electron
      microscopy) have made it possible to obtain three-dimensional structural
      information on larger systems, at higher resolution and with much less effort
      than in the past. Because these techniques often provide complementary
      information, combining them is particularly powerful for gaining comprehensive
      insights into complex systems, as illustrated by the recent structure
      determinations of the low-density lipoprotein receptor and the ribosome. SUMMARY:
      Structural biology is no longer exclusive to a few dedicated specialists. Many of
      its techniques are now easily accessible and can be used as tools in general life
      science research.

PMID- 12815341
TI  - Applications of gene therapy to kidney disease.
AB  - PURPOSE OF REVIEW: This review summarizes recent applications of somatic cell
      gene therapy to the treatment of monogenetic renal diseases, renal cell
      carcinoma, and for the induction of tolerance in solid organ transplantation. In
      addition, several new gene therapy techniques will be discussed including gene
      and messenger RNA repair strategies, as well as methods designed to modify the
      expression of normal genes that may have application in the treatment of
      multigenetic disorders. RECENT FINDINGS: Animal studies have demonstrated
      prolonged graft survival after the successful induction of tolerance to
      alloantigens via hematopoietic molecular chimerism. Ongoing clinical trials for
      renal cell carcinoma are encouraging, in that IL-2 gene therapy using non-viral
      vector systems can reduce the tumor burden. However, limited progress has been
      made towards applying gene therapy for the most common genetic disorders of the
      kidney, autosomal dominant polycystic kidney disease and Alport syndrome. Basic
      research on novel gene repair and expression modulation techniques provide
      additional gene therapy options for the treatment of viral infections such as HIV
      1 and monogenetic disorders. SUMMARY: Gene therapy holds enormous potential for
      the treatment of genetic and acquired diseases. Current pre-clinical studies and
      clinical trials provide encouraging results that gene therapy can become a useful
      treatment option. However, before gene therapy has widespread application,
      technical progress must be made in all aspects of treatment design, including
      optimizing vector and delivery systems and the ability to modify long-term cell
      populations such as stem cells.

PMID- 12815342
TI  - Stem cell biology and therapeutic applications.
AB  - PURPOSE OF REVIEW: Chronic diseases are common and deadly. Stem cell therapies
      have received intense interest for the repopulation of damaged or diseased
      tissues. A detailed understanding of the similarities and differences between
      embryonic stem cells and somatic stem cells will enhance our understanding of
      mechanisms of tissue repair or cellular augmentation. In addition, emerging
      technologies will be useful in the definition of the molecular regulation of the
      respective stem cell populations. RECENT FINDINGS: A number of postnatal tissues
      have a population of somatic stem cells, which function in the maintenance and
      repair of tissues. Using molecular technologies these somatic stem cell
      populations have been shown to be pluripotent when placed in a permissive
      environment. Recent studies have utilized emerging technologies to define a
      molecular signature of embryonic stem cells and selected somatic stem cell
      populations. These strategies will be useful for the definition of a molecular
      program that promotes a stem cell phenotype (i.e. stemness phenotype). SUMMARY:
      Recent studies suggest that embryonic and somatic stem cell populations hold
      promise as sources for tissue engineering. The use of cell biological and
      molecular technologies will enhance our understanding of embryonic and somatic
      stem cell populations and their molecular regulatory events that promote
      multipotentiation.

PMID- 12815343
TI  - Novel light microscopy imaging techniques in nephrology.
AB  - PURPOSE OF REVIEW: As more genomes are sequenced, the difficult task of
      characterizing the gene products of these genomes becomes the compelling mission
      of biological sciences. The melding of whole organ physiology with transgenic
      animal models, gene transfer methods and RNA silencing promises to form the next
      wave of scientific inquiry. A host of new microscopy imaging technologies enables
      researchers to directly visualize gene products, probe alterations in cell
      function in transgenic animals and map tissue organization. This review will
      describe these microscopy imaging techniques, their advantages, imaging
      properties and limitations. RECENT FINDINGS: New optical methods such as two
      photon confocal microscopy, fluorescence resonance energy transfer, and total
      internal fluorescence reflectance microscopy are increasingly being applied to
      extend our understanding of whole organ and renal epithelial function. Two-photon
      confocal microscopy has been used to image directly into the kidney of living
      animals. Fluorescence resonance energy transfer has been used to directly
      visualize transcription factor complexes within the nucleus while total internal
      fluorescence reflectance microscopy has permitted direct observation of protein
      delivery to the plasma membrane. SUMMARY: The application of these optical
      techniques along with the ability to label virtually any protein with a
      fluorescent tag will enable researchers to study cellular processes and whole
      organ function in vivo. Light microscopy methods will allow an advance from semi
      quantitative to quantitative approaches to problems of relevance to physiologists
      studying issues related to renal function.

PMID- 12815344
TI  - Stage I indexing to replace a failed implant in an edentulous arch: a clinical
      report.
AB  - Implant failure may complicate and lengthen a planned treatment. This article
      describes a modified stage I indexing technique for registering the position of
      an implant and replacing a failed implant, allowing prosthesis fabrication time
      and healing time to be coincidental. The clinician can proceed as originally
      planned with a minimal increase in overall treatment time.

PMID- 12815345
TI  - Combination therapies in the treatment of temporomandibular disorders: a clinical
      report.
AB  - Numerous implant systems exist that have the versatility to create a custom
      implant abutment with an anatomic shape. This clinical report describes the use
      of a digital scanner with CAD/CAM technology to create (copy mill) an
      anatomically shaped abutment.

PMID- 12815346
TI  - Fabrication of a sectional impression tray and sectional complete denture for a
      patient with microstomia and trismus: a clinical report.
AB  - This article describes techniques used to fabricate mandibular and maxillary
      sectional trays and a folding maxillary complete denture for a patient with
      limited oral opening caused by scleroderma. For the foldable denture, the
      anterior teeth had to be arranged on a second base and the hinge fitted at a
      location higher than the denture base. These 2 factors increased the thickness of
      the denture and limited the volume of the tongue. Nevertheless, a single-piece
      denture base provided the patient with ease in placement and removal of the
      denture.

PMID- 12815347
TI  - Geographic distribution of porcelain veneer preparation depth with various
      clinical techniques.
AB  - STATEMENT OF PROBLEM: Various clinical techniques have been advocated for uniform
      reduction of the tooth surface before a porcelain veneer restoration. Often these
      techniques do not produce a consistently uniform labial reduction. PURPOSE: The
      purpose of this study was to identify the degree of inconsistency on a geographic
      scale in the depth of labial reduction for porcelain veneers, resulting from the
      use of 3 clinical techniques. The technique of co-ordinate metrology was used to
      map the variations in the depth of the preparation. MATERIAL AND METHODS: A
      single operator using 3 techniques (dimples as depth guides, freehand, or depth
      grooves as depth guides) prepared 90 noncarious, unrestored extracted teeth to
      receive porcelain veneers (n=30). Impressions of the prepared and unprepared
      teeth were scanned with a co-ordinate measuring machine. In-house software was
      used to color-code the plotted images on the basis of the depth of preparation.
      Profile measurements were also made along the mid-labial sagital plane at the mid
      labial, incisal, and cervical regions, as well as along the mesial proximal and
      distal proximal areas along the mid-labial horizontal plane. The ideal depth
      range for the labial reduction was chosen to be 0.4 to 0.6 mm. One-way analysis
      of variance and the Bonferroni test were performed to determine the significance
      (P<.05) in the difference between the means of reductions achieved with the 3
      techniques. RESULTS: There was no statistically significant difference in the
      mean percentage area prepared to the ideal depth range (0.4 mm-0.6 mm), between
      dimple (44.59%), freehand (36.35%), and depth groove (38.43%) techniques. The
      difference in the mean percentage area of reduction greater than 0.6 mm between
      dimple (12.98%), freehand (29.66%), and dimple and depth groove (37.32%)
      techniques were statistically significant (P=.0000), but not between freehand and
      depth groove techniques. With the profile measurements it was seen that there
      were statistically significant differences in the mean depth between dimple (0.45
      mm) and depth groove (0.63 mm), and freehand (0.51 mm) and depth groove in the
      mid-buccal (P<.0004) and cervical (dimple = 0.48 mm, freehand = 0.52 mm, depth
      groove = 0.63 mm) (P<.0005) regions. There was statistically significant
      difference (P<.0000) in the mean depth between the dimple (0.39 mm) and freehand
      (0.30 mm), dimple and depth groove (0.50 mm), and freehand and depth groove
      techniques in the incisal area. In the mesial proximal region statistically
      significant difference (P<.0034) in the mean depth was found between the dimple
      (0.52 mm) and freehand (0.68 mm), and dimple and depth groove (0.64 mm)
      techniques only. In the distal proximal region, there was no statistically
      significant difference in the mean depth between dimple (0.55 mm), freehand (0.66
      mm), and depth groove (0.64 mm) techniques. CONCLUSION: The use of dimple
      technique showed a trend to greater consistency and fidelity in labial reduction
      to a depth of 0.4 to 0.6 mm. The 3 techniques for veneer preparations studied
      were associated with varying degrees of inconsistency in the distribution of
      depth of preparation within a tooth and between teeth in the same technique
      group.

PMID- 12815348
TI  - Fracture resistance of prepared teeth restored with bonded inlay restorations.
AB  - STATEMENT OF PROBLEM: intact, prepared, and restored human maxillary premolars.
      MATERIAL AND METHODS: Fifty intact, noncarious human maxillary premolars were
      divided into 5 groups of 10 and were mounted with their roots imbedded in
      autopolymerized acrylic. In the first group, the teeth were intact with no
      preparation. In the other 4 groups, Class II MOD preparations were made with a
      water-cooled high-speed hand piece. In 1 group, the cavity preparations were
      restored with bonded CAD/CAM ceramic inlays. In 2 groups, the preparations were
      restored with bonded CAD/CAM composite inlays (acid etched or air particle
      abraded). In the final group, the teeth were prepared but unrestored. Specimens
      were tested individually in a universal testing machine, in which a 4.82-mm
      diameter steel sphere plunger was mounted in the crosshead moving at 0.5 mm/min.
      The plunger contacted the facial and lingual triangular ridges beyond the margins
      of the restorations. Peak load to fracture (N) was measured for each specimen.
      Means were calculated and analyzed with analysis of variance (P</=.05). RESULTS:
      MOD preparations weakened the teeth by approximately 59%. Restoring the teeth
      with ceramic or composite inlays did not significantly strengthen the teeth under
      this testing system. Of the restored teeth, those restored with indirect
      composite inlays cemented following manufacturer's recommendations had the
      highest fracture resistance. CONCLUSION: Within the limitations of this study,
      under static compression load testing, bonded inlay restorations did not
      strengthen maxillary premolars with large MOD preparations.

PMID- 12815349
TI  - Tensile bond strength of four resin luting agents bonded to bovine enamel and
      dentin.
AB  - STATEMENT OF PROBLEM: The resistance to fracture of ceramic restorations depends
      on adequate bonding to tooth structure. The dental substrate and the types of
      resin luting agents used are believed to produce variability in adhesive
      properties. PURPOSE: The purpose of this study was to evaluate the tensile bond
      strength of 4 resin luting agents to bovine enamel and dentin. MATERIAL AND
      METHODS: Forty bovine incisors were embedded in acrylic resin and ground
      horizontally with water-cooled silicon carbide paper to expose enamel (20 teeth)
      and dentin at the enamel/dentin junction (20 teeth). Ten standard cone-shaped
      specimens with a 3-mm diameter base were prepared for each of the following resin
      cements: Resin Cement, Rely X ARC, Nexus, and Enforce. Five specimens of each
      material were bonded to enamel and the other 5 to dentin with these resin luting
      agents and their respective adhesive systems, according to the manufacturers'
      directions. After 7 days of storage in distilled water at 37 degrees C, specimens
      were subjected to tensile forces in a universal testing machine at a crosshead
      speed of 0.5 mm/min until fracture. Bond strength data were analyzed with
      analysis of variance for substrate and material. Means were compared with Tukey's
      test at the 0.05 level of significance. RESULTS: Analysis of variance disclosed
      that both substrate (P<.001) and material (P<.05) demonstrated statistically
      significant differences, but their interaction was not significant. The bond
      strengths (MPa) obtained for Resin Cement (11.5 +/- 3.0), Rely X ARC (11.4 +/-
      3.1), Nexus (10.0 +/- 1.4), and Enforce (11.8 +/- 2.8) were statistically the
      same for enamel. For dentin, bond strengths (MPa) for Rely X ARC (9.6 +/- 1.8),
      Resin Cement (9.3 +/- 0.9), and Enforce (7.8 +/- 2.9) were significantly higher
      than for Nexus (3.5 +/- 0.8). Significantly higher bond strengths (MPa) were also
      observed for enamel (11.2 +/- 2.5) than dentin (7.5 +/- 1.6). CONCLUSION: Within
      the limitations of this study, tensile bond strengths of resin luting agents to
      enamel were higher than those to dentin, and the bond strength values of Nexus to
      dentin were significantly lower (P<.05) than the other cements tested.

PMID- 12815350
TI  - The retention of complete crowns prepared with three different tapers and luted
      with four different cements.
AB  - STATEMENT OF PROBLEM: The role of adhesive properties of cements on the retentive
      strength of crowns with different degrees of taper is not clear. PURPOSE: This
      study evaluated the retention of full crowns prepared with 3 different tapers and
      cemented with 2 conventional and 2 adhesive resin cements. MATERIAL AND METHODS:
      One hundred twenty sound human molar teeth were assigned randomly to 1 of 12
      groups, (n=10). The groups represented the 4 cements: zinc phosphate (Fleck's), a
      conventional glass ionomer (Ketac-Cem); 2 adhesive resin cements (C&B Metabond
      and Panavia); and 3 tapers of 6-degrees, 12-degrees, and 24-degrees within each
      cement. Crowns were cast with a high noble alloy. The 6-degree taper was
      considered the control within each cement group. Retention was measured (MPa) by
      separating the metal crowns from the prepared teeth under tension on a universal
      testing machine. Analysis of variance was used to test the main effects on the
      retentive strength of full crowns, namely cements, tapers, and failure modes. The
      Fisher's multiple comparison test was used to evaluate the source of the
      differences. The chi(2) analyses were used to examine the relationships between
      failure types, cements, and tapers. All statistical tests were conducted at
      alpha=.05. RESULTS: There was a significant difference in the main effect cement
      (P<.0001) and taper (P=.0002). The mean retentive strength values of both Fleck's
      and Ketac-Cem were significantly lower than the mean retentive strength values of
      both C&B Metabond and Panavia (P<.0001). The retention of crowns prepared with 6
      degree taper was not significant from the 12-degree taper (P=.0666). The
      difference in retention was significant between the 6-degree taper and the 24
      degree taper (P<.0001) and between 12-degree taper and 24-degree taper (P=.0178).
      The types of failure were adhesive in the cement (65%), cohesive in the tooth
      (31%), and assembly failure (fracture of embedding resin) (4%). The type of
      failure was dependent on the degree of taper (P<.0001) and on the type of cement
      (P<.0042). CONCLUSION: Within the limitations of this study, the retentive values
      of the adhesive resins at 24-degree taper were 20% higher than the retentive
      values of the conventional cements at 6-degree taper. The use of resin luting
      agents yielded retention values that were double the values of zinc phosphate or
      conventional glass ionomer cement.

PMID- 12815351
TI  - Comparison of retentive systems for composites used as alternatives to porcelain
      in fixed partial dentures.
AB  - STATEMENT OF PROBLEM: The bond strength between framework metals and composites,
      used as alternatives to porcelain, requires further study because adhesive
      failures can promote microleakage, discoloration, and stains in composites.
      PURPOSE: The aim of this in vitro study was to analyze and compare the tensile
      strength between the base metal Ni-Cr alloys: (Wirocer and Wiron 99) and 2
      composites (Artglass and Solidex) with 2 types of mechanical retention (0.4-mm
      and 0.6-mm beads); 2 types of chemical treatment (Siloc system and Metal Photo
      Primer system) and the combination of both treatments on a metal framework; to
      verify whether these composite systems were strong enough to be used as
      alternatives to porcelain. MATERIAL AND METHODS: A total of 144 specimens,
      cylindrical metal rods (3 mm diameter x 60 mm length), were cast in Ni-Cr alloy
      (Wiron 99 or Wirocer), divided into 6 equal groups corresponding to 6 types of
      retention: airborne particle abrasion/control (A), chemical (C), mechanical with
      0.4-mm (M4) and 0.6-mm beads (M6), and chemical/mechanical with 0.4-mm (CM4) and
      0.6-mm beads (CM6). Composite rings formed around the rods (6.0 mm diameter X 2.0
      mm thickness) of Artglass or Solidex were light polymerized in the UniXS unit
      (wavelength range of 320-520 nm for 540s) according to the manufacturer's
      specifications. Specimens were invested, and their tensile strength was measured
      at fracture with an EMIC-MEM 2000 universal testing machine at a crosshead speed
      of 2.0 mm/min and 500 kgf load cell. Statistical analysis was carried out with
      analysis of variance and Tukey's test at significance level P=.01. RESULTS: The
      highest mean retention values were recorded for groups CM6 (63.57 MPa) and M6
      (63.05 MPa). The lowest mean retention values were recorded for groups A (30.63
      MPa) and C (25.07 MPa). No significant difference was found regarding the alloys
      used in this study (P<.01). There was a significant difference in shear strength
      (P<.01) between Solidex (52.33 MPa) and Artglass (43.18 MPa). CONCLUSION: Within
      the limitations of this study, mechanical retention with 0.6-mm beads and
      chemical/mechanical retention with 0.6-mm beads increased the metal-composite
      tensile bond strength. No significant difference was found between these 2
      retention systems. Chemical and airborne particle abrasion/control retentions
      were statistically weaker than the other types of retention tested. The retention
      means corresponding to the commercial-grade Ni-Cr alloys used were statistically
      different. The composite Solidex showed a tensile strength mean statistically
      higher than Artglass. All values observed were higher than that recommended for
      metal-ceramic dental restorative systems (25 MPa-ISO 9693).

PMID- 12815352
TI  - Monotonic flexure and fatigue strength of composites for provisional and
      definitive restorations.
AB  - STATEMENT OF PROBLEM: Ordinarily, the mechanical strength of composites is
      characterized by their flexural strength. Information as to the material's
      fatigue strength is seldom provided. PURPOSE: The purpose of this study was to
      compare the flexural strength and the resistance to fatigue loading of composites
      and an acrylic resin for provisional and definitive restorations. MATERIAL AND
      METHODS: Artglass, Colombus, and Targis (composites) and Jet, Protemp II, Protemp
      Garant, and Provipont DC (provisional restorations) were subjected to mechanical
      tests. Fatigue tests (MPa) (n = 30 specimens/group) were conducted with the
      rotating-bending cantilever design. Monotonic flexural strength (MPa) (n = 10)
      was determined in 3-point bending tests. Fatigue resistance was analyzed via the
      staircase procedure, and flexural strength was examined by use of the 2-parameter
      Weibull distribution (confidence intervals at 95%). RESULTS: The mean fatigue
      resistances (S(50)) in MPa +/- SD were: Targis, 62.1 +/- 7.0; Artglass, 58.5 +/-
      3.7; Colombus, 54.6 +/- 6.2; Provipont DC, 29.5 +/- 3.2; Protemp II, 23.1 +/-
      5.3; Jet, 22.8 +/- 8.3; Protemp Garant, 19.6 +/- 4.6. The flexure strengths
      (Weibull's S(0)) in MPa and their shape parameters (m) were: Colombus, 145.2
      (13.1); Targis, 110.3 (7.8); Artglass, 5.9 (5.4); Jet, 150.9 (17.3); Provipont
      DC, 97.3 (23.8); Protemp II, 57.9 (6.4); Protemp Garant, 54.2 (12.8). The S(50)
      of Targis was significantly higher than that of Colombus but not different from
      Artglass. In flexion, the S(0) of Colombus was significantly higher than that of
      Artglass and Targis. The S(50) ranged between 40% and 60% of the S(0) for the
      composites and between 15% and 30% for the provisional restorative materials.
      CONCLUSIONS: Correlations between monotonic flexure strength and resistance to
      fatigue loading were weak. Because fatigue tests are considered more pertinent
      than monotonic tests as to their predictive value, it is concluded that flexure
      strength data alone may not provide relevant information for long-term clinical
      performance. The material's resistance to fatigue loading should also be
      determined.

PMID- 12815353
TI  - Crestal bone loss proximal to oral implants in older and younger adults.
AB  - STATEMENT OF PROBLEM: Older adults often have bone loss and may be at risk of
      bone resorption around oral implants. PURPOSE: This study tested the hypothesis
      that there is no difference in crestal bone loss proximal to oral implants in the
      complete implant prosthesis sites of older and younger adults. MATERIAL AND
      METHODS: Two groups of 35 complete dental implant prosthesis sites (23 screw
      retained fixed prostheses and 12 bar-retained overdentures) were selected by
      matching sites in 32 older adults (60 to 74 years old with 166 Branemark
      implants) to sites in 34 younger adults (29 to 49 years old with 162 Branemark
      implants) on the basis of possible confounding factors including gender,
      prosthetic design, implant number, arch, year of surgery, and opposing dentition.
      Statistical comparisons (Mann-Whitney test at P<.05) were made of mean crestal
      bone level at loading and mean annual crestal bone loss during the first year,
      first to fourth year, after first year, and after fourth year of loading with
      periapical radiographic measurements of the vertical distance in millimeters from
      the apical edge of the implant collar to the most apical initial point of contact
      between the implant and bone. RESULTS: No significant differences were found
      between the groups. Mean bone levels at loading were 1.4 mm below the collar in
      both groups and mean annual crestal bone loss after the first year of loading was
      0.04 mm/y in both groups. However, significant differences were found between
      some old and young subgroups stratified by arch and prosthetic design.
      CONCLUSION: Within the limitations of this study, elders should expect no more
      rapid bone resorption around oral implants in edentulous jaws than that seen in
      young adults.

PMID- 12815354
TI  - Reducing the negative effects of chemical polishing in acrylic resins by use of
      an additional cycle of polymerization.
AB  - STATEMENT OF PROBLEM: The chemical polishing of dentures and orthodontic
      appliances is an efficient and time-saving technique. However, the process may
      adversely affect the physical properties of resin. PURPOSE: This study evaluated
      the effect of an additional polymerization cycle in a microwave or water bath on
      the physical properties of an autopolymerized acrylic resin submitted to chemical
      polishing. MATERIAL AND METHODS: Control groups comprised acrylic resin specimens
      submitted to mechanical (group 1) and chemical (group 2) polishing. Experimental
      groups comprised chemically polished specimens submitted to an additional cycle
      of polymerization in a microwave at 450 W for 3 minutes (group 3) or in a hot
      water bath at 65 degrees C for 1 hour (group 4). For the residual monomer test,
      10 standardized half-disc specimens (30 x 3 mm) were fabricated for each of the
      test groups, and daily ultraviolet spectrophotometric (206 nm) analyses were
      assessed for 13 days (microg/cm(2)). For transverse strength and internal Knoop
      hardness (KH) tests, 10 (65 x 10 x 2.5 mm) and 5 (32 x 10 x 2.5 mm) specimens
      were fabricated for each test group, respectively. Internal Knoop hardness
      (kg/mm(2)) was assessed at depths of 100, 700, and 1500 microm. Transverse
      strength (MPa) was measured with a 3-point bending test in a universal testing
      machine with a 10-kg load cell at a crosshead speed of 5 mm/min. The data were
      analyzed with 1-way analysis of variance, and the means were compared with
      Student's t test and Tukey-Kramer intervals (P<.05). RESULTS: At the end of the
      first day of the test, all groups showed significantly different residual monomer
      levels (P<.05). The groups in order of decreasing residual monomer were: group 2
      (1315.7 +/- 225.5 microg/cm(2)), group 3 (848.2 +/- 150.4 microg/cm(2)), group 4
      (295.1 +/- 81.6 microg/cm(2)), and group 1 (136.6 +/- 45.5 microg/cm(2)). After
      13 days of water storage, the lowest residual monomer levels were recorded for
      group 1 (4.6 +/- 1.6 microg/cm(2)). There were no significant differences among
      group 2 (11.3 +/- 3.1 microg/cm(2)), group 3 (9.6 +/- 1.5 microg/cm(2)), and
      group 4 (12.3 +/- 1.7 microg/cm(2)). Group 1 demonstrated the highest transverse
      strength (78.1 +/- 6.1 MPa); the other groups were not significantly different
      from each other. All groups exhibited lower KH values at the 100-microm depth
      than at 700- and 1500-microm depths. At the latter depths, group 4 specimens
      demonstrated the highest hardness values (18.0 +/- 0.5 and 18.8 +/- 0.7 kg/mm(2),
      respectively). CONCLUSION: Within the limitations of this study, additional
      polymerization with hot water reduced residual monomer content of chemically
      polished acrylic resins on the first day. Although additional polymerization
      increased the internal hardness of the material, however, it did not recover the
      transverse strength that was decreased by the chemical polishing.

PMID- 12815355
TI  - A reliable method for securing anterior denture teeth in denture bases.
AB  - STATEMENT OF PROBLEM: Bond failures continue to occur between resin denture teeth
      and the denture base. PURPOSE: This qualitative study examined a denture tooth
      modification to determine whether the joint produced between the denture tooth
      and the denture base resin was stronger than the materials from which it was
      composed. MATERIAL AND METHODS: Modified and unmodified resin denture teeth were
      processed to a denture base and stressed until fracture occurred. The fragments
      were saved, labeled, examined, and evaluated. RESULTS: The unmodified resin
      denture teeth, which were displaced from the denture, exhibited no evidence of a
      bond to the denture base. The modified resin denture teeth fractured before
      separation could occur. CONCLUSION: Within the limitations of this study, the
      cingulum ledge lock modification produced a mechanical union of the resin denture
      teeth tested to the denture base material tested that was stronger than the
      materials from which the lock was composed.

PMID- 12815356
TI  - The evolution of the obturator framework design.
AB  - This brief overview of the progress and evolution of philosophies of obturator
      framework designs was accomplished by hand, as well as via Medline. It begins in
      1530 ad with Ambrose Pare who described the first button-shaped sponge and metal
      obturator, and continues through the formation of the American Academy of
      Maxillofacial Prosthetics and the development of the specialty. It concludes with
      a simplified discussion of complex surgical-prosthetic coordination and the use
      of vascularized free flaps with osseointegrated dental implants.

PMID- 12815357
TI  - Predictable implant placement with a diagnostic/surgical template and advanced
      radiographic imaging.
AB  - The technique described facilitates precise dental implant placement. A barium
      coated template with external guide wires used in conjunction with a computed
      tomography scan and interactive software may provide superior presurgical
      diagnostics, treatment planning, and prosthetically directed implant placement.
      Measurements predetermined on the computed tomography scan can be transferred
      accurately to the diagnostic/surgical template by use of a precision milled
      cylinder placed into the template at the proper angulation and linear dimensions.
      The diagnostic/surgical template shows the surgeon the optimal position for
      implant placement, thus establishing greater clinical confidence when placing
      implants.

PMID- 12815358
TI  - An impression technique for optimal positioning of precision attachments for
      removable partial dentures.

PMID- 12815359
TI  - Modified double-gloving technique for extra finger protection in prosthodontic
      treatment.

PMID- 12815360
TI  - Sequence and function in pharmacogenomics.

PMID- 12815361
TI  - Microarrays as toxin sensors.

PMID- 12815362
TI  - Pharmacogenomic effects on therapy for acute lymphoblastic leukemia in children.

PMID- 12815363
TI  - Pharmacogenomics of human UDP-glucuronosyltransferase enzymes.
AB  - UDP-glucuronosyltransferase (UGT) enzymes comprise a superfamily of key proteins
      that catalyze the glucuronidation reaction on a wide range of structurally
      diverse endogenous and exogenous chemicals. Glucuronidation is one of the major
      phase II drug-metabolizing reactions that contributes to drug biotransformation.
      This biochemical process is also involved in the protection against environmental
      toxicants, carcinogens, dietary toxins and participates in the homeostasis of
      numerous endogenous molecules, including bilirubin, steroid hormones and biliary
      acids. Over the years, significant progress was made in the field of
      glucuronidation, especially with regard to the identification of human UGTs,
      study of their tissue distribution and substrate specificities. More recently,
      the degree of allelic diversity has also been revealed for several human UGT
      genes. Some polymorphic UGTs have demonstrated a significant pharmacological
      impact in addition to being relevant to drug-induced adverse reactions and cancer
      susceptibility. This review focuses on human UGTs, the description of the nature
      of polymorphic variations and their functional impact. The pharmacogenomic
      implication of polymorphic UGTs is presented, more specifically the role of UGT
      polymorphisms in modifying cancer risk and their impact on individual risk to
      drug-induced toxicities.

PMID- 12815364
TI  - Human dopamine transporter gene variation: effects of protein coding variants
      V55A and V382A on expression and uptake activities.
AB  - The human dopamine transporter (DAT, SLC6A3) is an important 15 exon gene for
      dopamine neurotransmission and dopamine recycling. Common exon 15 variable number
      tandem repeat variants can be associated with attention deficit/hyperactivity
      disorder. Rarer single nucleotide polymorphisms produce missense variants
      including V55A and V382A. We now report studies of the functional influences of
      these DAT protein-coding variants. In COS cell transient-expression assays, V382A
      displays about half of the dopamine uptake velocity Vmax and cocaine analog
      binding Bmax values of wildtype DAT. V382A lowers dopamine's potency in
      inhibiting cocaine analog binding by six-fold. Cells expressing V382A or mixtures
      of V382A and wildtype DAT both display reduced plasma membrane and increased
      perinuclear expression, consistent with dominant effects of V328A on expression.
      V55A expresses normally but reveals a 1.7-fold-lower Km for dopamine uptake.
      Individuals with these human DAT protein variants could display altered dopamine
      systems.

PMID- 12815365
TI  - Generation and analysis of mice with a targeted disruption of the arylamine N
      acetyltransferase type 2 gene.
AB  - Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolising
      enzymes, linked to cancer susceptibility in a variety of tissues. In humans and
      in mice there are multiple NAT isoforms. To identify whether the different
      isoforms represent inbuilt redundancy or whether they have unique roles, we have
      generated mice with a null allele of Nat2 by gene targeting. This mouse line
      conclusively demonstrates that the different isoforms have distinct functions
      with no compensatory expression in the Nat2 null animals of the other isoforms.
      In addition, we have used the transgenic line to show the pattern of Nat2
      expression during development. Although Nat2 is not essential for embryonic
      development, it has a widespread tissue distribution from at least embryonic day
      9.5. This mouse line now paves the way for the teratological role of Nat2 to be
      tested.

PMID- 12815366
TI  - Thiopurine methyltransferase polymorphisms in a Brazilian population.
AB  - Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine
      drugs. Low-activity phenotypes are correlated with several mutations in the TPMT
      gene. Polymorphisms of TPMT have been reported for Caucasians, African-Americans
      and Asians. Since ethnic differences have been demonstrated worldwide, it remains
      to be elucidated in Brazil. The Brazilian population is the result of five
      centuries of interethnic crosses between peoples from almost all continents as
      well as autochthonous Amerindians, all forming the fifth largest and one of the
      most heterogeneous populations in the world. The frequency of six allelic
      variants of the TPMT gene, *2 (G238C) (2.2%), *3A (G460A and A719G) (1.5%), *3B
      (G460A) (0.2%), *3C (A719G) (1.0%), *5 (0%) and *6 (0%) were determined in
      Brazilian subjects using polymerase chain reaction (PCR)-RFLP and allele-specific
      PCR-based assays. This study provides the first analysis of TPMT mutant allele
      frequency in a sample of the Brazilian population.

PMID- 12815367
TI  - Target validation in hypoxia-induced vascular remodeling using
      transcriptome/metabolome analysis.
AB  - The present study describes combined transcriptome and metabolome analysis for
      therapeutic target validation in hypoxia-induced vascular remodeling. Exposure to
      hypoxic conditions resulted in the upregulation of S100C mRNA and increased
      taurine (2-aminoethanesulfonic acid) content in the rat lung, as demonstrated by
      differential display and amino-acid content analysis. Hypoxia resulted in
      transcriptional activation of the S100C promoter through hypoxia-inducible factor
      1 (HIF-1). Taurine suppressed HIF-1-mediated increases in S100C transcription.
      Moreover, oral taurine administration attenuated vascular remodeling in hypoxic
      rat lung, whereas depletion of endogenous taurine by administration of beta
      alanine resulted in increased vascular remodeling. Inhibition of HIF
      transcription by taurine may be of therapeutic benefit in preventing hypoxia
      induced vascular remodeling. In conclusion, we used transcriptome and metabolome
      analysis to identify a therapeutic low-molecular-weight ligand that plays a
      critical role in hypoxia-induced vascular remodeling. These techniques provided
      an excellent strategy for screening and validation of targets.

PMID- 12815368
TI  - Post-traumatic inflammation following spinal cord injury.
AB  - Inflammatory reaction following a spinal cord injury (SCI) contributes
      substantially to secondary effects, with both beneficial and devastating effects.
      This review summarizes the current knowledge concerning the structural features
      (vascular, cellular, and biochemical events) of SCI and gives an overview of the
      regulation of post-traumatic inflammation.

PMID- 12815369
TI  - Fixed vs dynamic plate complications following multilevel anterior cervical
      corpectomy and fusion with posterior stabilization.
AB  - STUDY DESIGN: Comparison of fixed vs dynamic plate complications in cervical
      surgery. SETTING: : New York, USA. METHODS: Anterior cervical plate-related
      complications were evaluated following 66 anterior cervical corpectomy and fusion
      (ACF) with posterior stabilization (PWF) procedures performed in patients with
      ossification of the posterior longitudinal ligament (OPLL). Clinical data were
      comparable for both patient populations. Patients averaged between 52 and 53
      years of age. The male to female ratio was approximately 2:1. Surgery addressed
      MR and CT documented multilevel OPLL in all patients accompanied by spondylosis
      and stenosis. Preoperatively average Nurick Grades ranged from 3.6 to 3.7.
      Anterior cervical corpectomies included an average of 2.6-3.0 vertebral bodies,
      while PWF covered seven levels. Fixed plates were applied in the initial 38
      patients, while the latter 28 patients had dynamic plates (ABC, Aesculap,
      Tuttlingen, Germany) applied. Halo devices were used until fusion was documented
      on both X-ray and 2D-CT studies. Patients were followed-up for an average of 5.4
      years in the fixed-plated groups, and 2.7 years in the dynamic-plated population.
      RESULTS: CT and dynamic X-ray confirmed that fusion occurred an average of 4.5
      4.9 months postoperatively. Five (13%) fixed plates (Medtronic, Sofamor Danek,
      Memphis, TN, USA) failed warranting secondary surgery, while only one (3.6%)
      dynamic-plated patient developed a pseudarthrosis and required secondary
      posterior fusion. DISCUSSION/CONCLUSION: Higher failure rates follow multilevel
      ACF as compared with anterior diskectomy and fusion required to resect multilevel
      OPLL. Vaccaro et al observed a 9% failure rate following two-level ACFs and 50%
      failure rate following three-level ACFs performed with fixed plates. In this
      series, the plate extrusion rate was reduced to 3.6% when dynamic plates were
      applied.

PMID- 12815370
TI  - Classification of spinal injuries based on the essential traumatic spinal
      mechanisms.
AB  - STUDY DESIGN: A biomechanical unitary classification of spinal injuries is
      proposed. OBJECTIVE: To present an evaluation of spinal injuries based on the
      essential traumatic spinal mechanisms: axial deformation, torsion, translation
      and combined mechanisms in connection with the concept of the stabilizing axial
      spinal pillar. SETTING: Hospital 'Sf. Treime', Iasi, Romania. METHODS: The
      essential mechanisms of spinal injuries are considered: (1) axial deformation
      with (a) compression (centric or eccentric), most often eccentric, including
      compression in flexion or extension; (b) spinal elongation with distraction as
      centric elongation, but frequently axial eccentric elongation and a flexion or
      extension injury; (2) torsion or axial spinal rotation, (3) segmental
      translation, with a shearing version for the double translation and (4) combined
      mechanisms - the most frequent situation. Over 300 patients with spinal injuries
      were analysed and the spinal instability was determined using the criteria of
      clinical instability. The cases of spinal instability were studied in connection
      with the types of lesion of the central axial spinal pillar. RESULTS: All cases
      with lesions of the central axial spinal pillar had traumatic spinal instability.
      The spinal instability was absent in cases of isolated lesions of the anterior or
      posterior secondary pillar. The X-ray and spinal CT analysis of the traumatic
      spinal lesions showed the types of lesions and specified the mechanisms of spinal
      injuries. The combined mechanisms were responsible for the majority of the spinal
      injuries. CONCLUSIONS: Spinal instability occurs because of the lesion of the
      central axial spinal pillar The types of lesions of the central spinal pillar and
      of the secondary spinal pillars are determined by the essential traumatic spinal
      mechanisms: axial deformation (with compression or elongation), axial rotation,
      translation and most frequently the above combined mechanisms.

PMID- 12815371
TI  - A 7-year follow-up of sacral anterior root stimulation for bladder control in
      patients with a spinal cord injury: quality of life and users' experiences.
AB  - STUDY DESIGN: Cross-sectional descriptive study. OBJECTIVES: To assess long-term
      effects and quality of life (QoL) of using sacral anterior root stimulation
      (SARS) in spinal cord injured patients. SETTING: Neurosurgical and Urological
      Departments of a large teaching hospital and a large rehabilitation centre in the
      Netherlands. METHODS: In all, 42 patients with complete spinal cord injury (SCI)
      implanted between 1987 and 2000 were included. A questionnaire was constructed to
      determine complications, technical failures and personal experiences of the
      patients. The Qualiveen questionnaire was used and the outcome was compared with
      data obtained from a reference group of 400 SCI patients with neurogenic bladder
      problems not using the bladder controller. The Qualiveen questionnaire measures
      disease-specific aspects in four domains with respect to limitations,
      constraints, fears and feelings and general QoL aspects, suitable for use in SCI
      patients with urinary disorders. RESULTS: The results of 37 patients are
      presented. Our results with the bladder controller with respect to medical and
      technical complications and infection rates are similar to the results presented
      by others. From users' experiences, the most important advantages reported were a
      decreased infection rate (68%), improved social life (54%) and continence (54%).
      Comparison of the obtained results of our patient group with the Qualiveen
      questionnaire with a reference group not using the bladder controller indicates
      that the specific impact of urinary disorders in the four domains on QoL is
      reduced and that general QoL is improved. CONCLUSION: SARS is effective and safe
      for neurogenic bladder management in patients with complete SCI. Users'
      experiences are positive. Furthermore, this therapy seems to reduce the effects
      of urinary-disorder-specific QoL aspects, and to increase the QoL in general.

PMID- 12815372
TI  - Atypical intradural spinal tuberculosis: report of three cases.
AB  - OBJECTIVE: To report three cases of intradural spinal tuberculosis (TB) by
      calling attention to atypical forms of spinal TB. SETTING: A University Hospital,
      Istanbul, Turkey. METHODS: Histopathological, radiological, surgical and physical
      examination findings of three patients with spinal TB were retrospectively
      reviewed. RESULTS: Based on histopathological, surgical and radiological
      findings, diagnosis of intramedullary abscess had been made in the first case and
      early and late phases of arachnoiditis in the other two patients, respectively.
      The clinical outcome was evaluated as satisfactory for the patient with
      intramedullary abscess who had been treated with medical and surgical
      interventions. The remaining two patients with arachnoiditis, who had been
      treated by shunting or simple decompression, had a relatively less favorable
      clinical outcome. CONCLUSION: Spinal TB, in its atypical forms, is a rare
      clinical entity and low index of suspicion on the part of the surgeon may result
      in misdiagnosis such as neoplasm. In cases presenting with an intraspinal mass
      lesion, possibility of a tuberculous abscess and/or a granuloma should be
      considered in the differential diagnosis.

PMID- 12815373
TI  - Rupture of tuberculous spinal abscess resulting in tuberculous empyema and
      chylothorax.
AB  - STUDY DESIGN: Case report with a review of scientific literature. OBJECTIVE: To
      describe the course of tuberculous spinal disease (Pott's disease) complicated by
      pyogenic and tuberculous empyema, and chylothorax as there has been an increase
      in the numbers of notified cases of tuberculosis in the UK(1). To the best of our
      knowledge, a similar case has not been reported previously in the UK, although
      there has been a report of bilateral chylothorax associated with Pott's disease.
      SETTING: A national spinal injuries unit in a Scottish university teaching
      hospital. METHODS: Review of literature on the chemotherapy of spinal
      tuberculosis and the role of streptokinase in the treatment of empyema and the
      relation between spinal tuberculosis, empyema and chylothorax. RESULTS: Although
      spinal tuberculosis was recognised and treated appropriately with chemotherapy,
      the patient sustained pleural involvement with later development of both empyema
      and chylothorax. CONCLUSION: The case highlights the difficulties in the
      treatment of tuberculosis of the spine inspite of the presence of fully sensitive
      organisms and early institution of appropriate chemotherapy. In the absence of
      surgical debridement, the duration and dosage of chemotherapy as practised in the
      initial period may have to be prolonged into the continuation phase. The thoracic
      duct can be damaged either because of extension of the tuberculosis itself or
      because of instillation of intrapleural streptokinase for treatment of pleural
      empyema leading to chylothorax. There is a need for randomised trials of
      intrapleural streptokinase treatment in tuberculous empyema.

PMID- 12815374
TI  - Spinal cord compression due to tumoral idiopatic calcinosis.
AB  - STUDY DESIGN: A case of thoracic spinal cord compression due to tumoral
      calcinosis (TC) is reported. SETTING: Galiza, Spain. CASE REPORT: A 59-year-old
      man was admitted to our hospital with a 2-month history of gradual leg weakness
      and sensory deficit. The neurological examination revealed paraparesis with T12
      sensory level. Magnetic resonance imaging (MRI) showed an extradural right
      posterolateral mass at T11-T12 level, resulting in a marked spinal cord
      compression. He underwent T11-T12 laminectomy and mass excision. Histological
      examination finally led to the diagnosis of TC. CONCLUSION: TC is an uncommon
      cause of mass lesions of the spine. Since there is no typical spine TC MRI
      appearance, the final diagnosis is done by histological studies. TC should be
      considered in differential diagnosis of spinal cord compression and constitutes a
      treatable cause of paraparesis.

PMID- 12815375
TI  - Comment on "Pitfall in insertion of suprapubic catheter in patients with spinal
      cord injury".

PMID- 12815377
TI  - Comment on "Neurogenic heterotopic ossification in spinal cord injury" article.

PMID- 12815379
TI  - Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors.
AB  - In the 1950s and 1960s, it became apparent that elevated concentrations of plasma
      cholesterol were a major risk factor for the development of coronary heart
      disease, which led to the search for drugs that could reduce plasma cholesterol.
      One possibility was to reduce cholesterol biosynthesis, and the rate-limiting
      enzyme in the cholesterol biosynthetic pathway, 3-hydroxy-3-methyl-glutaryl-CoA
      (HMG-CoA) reductase, was a natural target. Here, I describe the discovery and
      development of lovastatin--the first approved inhibitor of HMG-CoA reductase--and
      the clinical trials that have provided the evidence for the ability of drugs in
      this class to reduce the morbidity and mortality associated with cardiovascular
      disease.

PMID- 12815380
TI  - Making better drugs: Decision gates in non-clinical drug development.
AB  - Drug development is a risky business. Success or failure often depends on
      selecting one or two molecules for development from many choices offered by the
      engines of high-throughput discovery. A lead candidate needs to possess adequate
      bioactivity, appropriate physical-chemical properties to enable formulation
      development, the ability to cross crucial membranes, reasonable metabolic
      stability and appropriate safety and efficacy in humans. Predicting how a drug
      will behave in humans before clinical testing requires a battery of sophisticated
      in vitro tests that complement traditional in vivo animal safety assessments.
      This review discusses how to strategically identify which non-clinical studies
      should be performed to provide the required guidance and comfort to stakeholders
      involved in clinical drug testing.

PMID- 12815381
TI  - Targeting JNK for therapeutic benefit: from junk to gold?
AB  - The c-Jun NH(2)-terminal kinases (JNKs) phosphorylate and activate members of the
      activator protein-1 (AP-1) transcription factor family and other cellular factors
      implicated in regulating altered gene expression, cellular survival and
      proliferation in response to cytokines and growth factors, noxious stimuli and
      oncogenic transformation. Because these events are commonly associated with the
      pathogenesis of a number of human diseases, the potential of JNK inhibitors as
      therapeutics has attracted considerable interest. Here we discuss the evidence
      supporting the application of JNK inhibitors in inflammatory, vascular,
      neurodegenerative, metabolic and oncological diseases in humans, and describe the
      present status of drug discovery targeting JNK.

PMID- 12815382
TI  - The bicyclam AMD3100 story.
AB  - The discovery and development of the bicyclam AMD3100--a chemokine receptor
      antagonist--has highlighted the therapeutic potential of such compounds in HIV
      infection, inflammatory diseases, cancer and stem-cell mobilization. Here, I
      describe the development process of AMD3100, which began about 15 years ago with
      the isolation of an impurity, and the basis for the clinical application of
      AMD3100 and its congeners.

PMID- 12815383
TI  - Large-scale manufacture of peptide therapeutics by chemical synthesis.
AB  - The large-scale commercial production of a 36-amino-acid peptide by chemical
      synthesis has been demonstrated in the development of enfuvirtide (T-20 or
      Fuzeon), a first-in-class membrane fusion inhibitor for the treatment of HIV. The
      rationale behind route selection and the scale-up of the process used to
      manufacture enfuvirtide are discussed.

PMID- 12815384
TI  - Pros and cons of centralization.

PMID- 12815385
TI  - Silence of the neuroengineers.

PMID- 12815387
TI  - Whaling group backs conservation.

PMID- 12815386
TI  - US army attacked over published patent for 'bioweapons grenade'.

PMID- 12815388
TI  - Traditional wheat breeder fights for funding.

PMID- 12815389
TI  - German reform plan arouses fears for autonomy.

PMID- 12815390
TI  - Clinical data marshalled to treat HIV.

PMID- 12815391
TI  - China and Germany join forces over SARS.

PMID- 12815392
TI  - British panel bans use of antidepressant to treat children.

PMID- 12815393
TI  - Researchers rattled as Kyoto Protocol hangs in the balance.

PMID- 12815394
TI  - Ecologists seek to turn tide on Colorado River.

PMID- 12815395
TI  - Hive beetle causes a buzz in Europe.

PMID- 12815397
TI  - Remote control.

PMID- 12815398
TI  - The crystal's in the mail...

PMID- 12815400
TI  - Britannica: source of a passion for physics.

PMID- 12815399
TI  - How e-mail raises the spectre of a digital Dark Age.

PMID- 12815401
TI  - Britannica: which edition inspired Schwinger?

PMID- 12815407
TI  - The supernova connection.

PMID- 12815408
TI  - Tales of the Y chromosome.

PMID- 12815410
TI  - Ups and downs in the Red Sea.

PMID- 12815411
TI  - Versatile assembler.

PMID- 12815412
TI  - Volume control.

PMID- 12815413
TI  - Beyond the inflationary border.

PMID- 12815414
TI  - Rings of excitement.

PMID- 12815415
TI  - Degradation ensures integrity.

PMID- 12815417
TI  - The missing link in Ginkgo evolution.

PMID- 12815418
TI  - Opposite thermosensor in fruitfly and mouse.

PMID- 12815419
TI  - Producing decaffeinated coffee plants.

PMID- 12815420
TI  - Mycorrhizal weathering in base-poor forests.

PMID- 12815422
TI  - The male-specific region of the human Y chromosome is a mosaic of discrete
      sequence classes.
AB  - The male-specific region of the Y chromosome, the MSY, differentiates the sexes
      and comprises 95% of the chromosome's length. Here, we report that the MSY is a
      mosaic of heterochromatic sequences and three classes of euchromatic sequences: X
      transposed, X-degenerate and ampliconic. These classes contain all 156 known
      transcription units, which include 78 protein-coding genes that collectively
      encode 27 distinct proteins. The X-transposed sequences exhibit 99% identity to
      the X chromosome. The X-degenerate sequences are remnants of ancient autosomes
      from which the modern X and Y chromosomes evolved. The ampliconic class includes
      large regions (about 30% of the MSY euchromatin) where sequence pairs show
      greater than 99.9% identity, which is maintained by frequent gene conversion (non
      reciprocal transfer). The most prominent features here are eight massive
      palindromes, at least six of which contain testis genes.

PMID- 12815423
TI  - Structure in the early afterglow light curve of the gamma-ray burst of 29 March
      2003.
AB  - Gamma-ray bursts (GRBs) are energetic explosions that for 0.01-100 s are the
      brightest gamma-ray sources in the sky. Observations of the early evolution of
      afterglows are expected to provide clues about the nature of the bursts, but
      their rapid fading has hampered such studies; some recent rapid localizations of
      bursts have improved the situation. Here we report an early detection of the very
      bright afterglow of the burst of 29 March 2003 (GRB030329). Our data show that,
      even early in the afterglow phase, the light curve shows unexpectedly complicated
      structures superimposed on the fading background.

PMID- 12815424
TI  - The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003.
AB  - Past studies of cosmological gamma-ray bursts (GRBs) have been hampered by their
      extreme distances, resulting in faint afterglows. A nearby GRB could potentially
      shed much light on the origin of these events, but GRBs with a redshift z <or=
      0.2 have been estimated to occur only rarely, about once per decade. Here we
      report the discovery of the bright optical afterglow emission from the burst of
      29 March 2003 (GRB030329; ref. 2). The brightness of the afterglow and the prompt
      report of its position resulted in extensive follow-up observations at many
      wavelengths, along with the measurement of the redshift, z = 0.169 (ref. 4). The
      gamma-ray and afterglow properties of GRB030329 are similar to those of GRBs at
      cosmological redshifts. Observations have already identified the progenitor as a
      massive star that exploded as a supernova.

PMID- 12815425
TI  - A very energetic supernova associated with the gamma-ray burst of 29 March 2003.
AB  - Over the past five years evidence has mounted that long-duration (>2 s) gamma-ray
      bursts (GRBs)-the most luminous of all astronomical explosions-signal the
      collapse of massive stars in our Universe. This evidence was originally based on
      the probable association of one unusual GRB with a supernova, but now includes
      the association of GRBs with regions of massive star formation in distant
      galaxies, the appearance of supernova-like 'bumps' in the optical afterglow light
      curves of several bursts and lines of freshly synthesized elements in the spectra
      of a few X-ray afterglows. These observations support, but do not yet
      conclusively demonstrate, the idea that long-duration GRBs are associated with
      the deaths of massive stars, presumably arising from core collapse. Here we
      report evidence that a very energetic supernova (a hypernova) was temporally and
      spatially coincident with a GRB at redshift z = 0.1685. The timing of the
      supernova indicates that it exploded within a few days of the GRB, strongly
      suggesting that core-collapse events can give rise to GRBs, thereby favouring the
      'collapsar' model.

PMID- 12815426
TI  - Beating the superparamagnetic limit with exchange bias.
AB  - Interest in magnetic nanoparticles has increased in the past few years by virtue
      of their potential for applications in fields such as ultrahigh-density recording
      and medicine. Most applications rely on the magnetic order of the nanoparticles
      being stable with time. However, with decreasing particle size the magnetic
      anisotropy energy per particle responsible for holding the magnetic moment along
      certain directions becomes comparable to the thermal energy. When this happens,
      the thermal fluctuations induce random flipping of the magnetic moment with time,
      and the nanoparticles lose their stable magnetic order and become
      superparamagnetic. Thus, the demand for further miniaturization comes into
      conflict with the superparamagnetism caused by the reduction of the anisotropy
      energy per particle: this constitutes the so-called 'superparamagnetic limit' in
      recording media. Here we show that magnetic exchange coupling induced at the
      interface between ferromagnetic and antiferromagnetic systems can provide an
      extra source of anisotropy, leading to magnetization stability. We demonstrate
      this principle for ferromagnetic cobalt nanoparticles of about 4 nm in diameter
      that are embedded in either a paramagnetic or an antiferromagnetic matrix.
      Whereas the cobalt cores lose their magnetic moment at 10 K in the first system,
      they remain ferromagnetic up to about 290 K in the second. This behaviour is
      ascribed to the specific way ferromagnetic nanoparticles couple to an
      antiferromagnetic matrix.

PMID- 12815427
TI  - Sea-level fluctuations during the last glacial cycle.
AB  - The last glacial cycle was characterized by substantial millennial-scale climate
      fluctuations, but the extent of any associated changes in global sea level (or,
      equivalently, ice volume) remains elusive. Highstands of sea level can be
      reconstructed from dated fossil coral reef terraces, and these data are
      complemented by a compilation of global sea-level estimates based on deep-sea
      oxygen isotope ratios at millennial-scale resolution or higher. Records based on
      oxygen isotopes, however, contain uncertainties in the range of +/-30 m, or +/-1
      degrees C in deep sea temperature. Here we analyse oxygen isotope records from
      Red Sea sediment cores to reconstruct the history of water residence times in the
      Red Sea. We then use a hydraulic model of the water exchange between the Red Sea
      and the world ocean to derive the sill depth-and hence global sea level-over the
      past 470,000 years (470 kyr). Our reconstruction is accurate to within +/-12 m,
      and gives a centennial-scale resolution from 70 to 25 kyr before present. We find
      that sea-level changes of up to 35 m, at rates of up to 2 cm yr(-1), occurred,
      coincident with abrupt changes in climate.

PMID- 12815428
TI  - Archaean ultra-depleted komatiites formed by hydrous melting of cratonic mantle.
AB  - Komatiites are ultramafic volcanic rocks containing more than 18 per cent MgO
      (ref. 1) that erupted mainly in the Archaean era (more than 2.5 gigayears ago).
      Although such compositions occur in later periods of Earth history (for example,
      the Cretaceous komatiites of Gorgona Island), the more recent examples tend to
      have lower MgO content than their Archaean equivalents. Komatiites are also
      characterized by their low incompatible-element content, which is most consistent
      with their generation by high degrees of partial melting (30-50 per cent).
      Current models for komatiite genesis include the melting of rock at great depth
      in plumes of hot, diapirically rising mantle or the melting of relatively shallow
      mantle rocks at less extreme, but still high, temperatures caused by fluxing with
      water. Here we report a suite of ultramafic lava flows from the Commondale
      greenstone belt, in the southern part of the Kaapvaal Craton, which represents a
      previously unrecognized type of komatiite with exceptionally high forsterite
      content of its igneous olivines, low TiO(2)/Al(2)O(3) ratio, high silica content,
      extreme depletion in rare-earth elements and low Re/Os ratio. We suggest a model
      for their formation in which a garnet-enriched residue left by earlier cratonic
      volcanism was melted by hydration from a subducting slab.

PMID- 12815429
TI  - Automatic gain control in the echolocation system of dolphins.
AB  - In bats and technological sonars, the gain of the receiver is progressively
      increased with time after the transmission of a signal to compensate for acoustic
      propagation loss. The current understanding of dolphin echolocation indicates
      that automatic gain control is not a part of their sonar system. In order to test
      this understanding, we have performed field measurements of free-ranging
      echolocating dolphins. Here we show that dolphins do possess an automatic gain
      control mechanism, but that it is implemented in the transmission phase rather
      than the receiving phase of a sonar cycle. We find that the amplitude of the
      dolphins' echolocation signals are highly range dependent; this amplitude
      increases with increasing target range, R, in a 20 log(R) fashion to compensate
      for propagation loss. If the echolocation target is a fish school with many sound
      scatterers, the echoes from the school will remain nearly constant with range as
      the dolphin closes in on it. This characteristic has the same effect as time
      varying gain in bats and technological sonar when considered from a sonar system
      perspective.

PMID- 12815430
TI  - Involvement of Notch and Delta genes in spider segmentation.
AB  - It is currently debated whether segmentation in different animal phyla has a
      common origin and shares a common genetic mechanism. The apparent use of
      different genetic networks in arthropods and vertebrates has become a strong
      argument against a common origin of segmentation. Our knowledge of arthropod
      segmentation is based mainly on the insect Drosophila, in which a hierarchical
      cascade of transcription factors controls segmentation. The function of some of
      these genes seems to be conserved among arthropods, including spiders, but not
      vertebrates. The Notch pathway has a key role in vertebrate segmentation
      (somitogenesis) but is not involved in Drosophila body segmentation. Here we show
      that Notch and Delta genes are involved in segmentation of another arthropod, the
      spider Cupiennius salei. Expression patterns of Notch and Delta, coupled with RNA
      interference experiments, identify many similarities between spider segmentation
      and vertebrate somitogenesis. Our data indicate that formation of the segments in
      arthropods and vertebrates may have shared a genetic programme in a common
      ancestor and that parts of this programme have been lost in particular descendant
      lineages.

PMID- 12815431
TI  - Somatosensory basis of speech production.
AB  - The hypothesis that speech goals are defined acoustically and maintained by
      auditory feedback is a central idea in speech production research. An alternative
      proposal is that speech production is organized in terms of control signals that
      subserve movements and associated vocal-tract configurations. Indeed, the
      capacity for intelligible speech by deaf speakers suggests that somatosensory
      inputs related to movement play a role in speech production-but studies that
      might have documented a somatosensory component have been equivocal. For example,
      mechanical perturbations that have altered somatosensory feedback have
      simultaneously altered acoustics. Hence, any adaptation observed under these
      conditions may have been a consequence of acoustic change. Here we show that
      somatosensory information on its own is fundamental to the achievement of speech
      movements. This demonstration involves a dissociation of somatosensory and
      auditory feedback during speech production. Over time, subjects correct for the
      effects of a complex mechanical load that alters jaw movements (and hence
      somatosensory feedback), but which has no measurable or perceptible effect on
      acoustic output. The findings indicate that the positions of speech articulators
      and associated somatosensory inputs constitute a goal of speech movements that is
      wholly separate from the sounds produced.

PMID- 12815432
TI  - The influence of visual motion on fast reaching movements to a stationary object.
AB  - One of the most important functions of vision is to direct actions to objects.
      However, every time that vision is used to guide an action, retinal motion
      signals are produced by the movement of the eye and head as the person looks at
      the object or by the motion of other objects in the scene. To reach for the
      object accurately, the visuomotor system must separate information about the
      position of the stationary target from background retinal motion signals-a long
      standing problem that is poorly understood. Here we show that the visuomotor
      system does not distinguish between these two information sources: when observers
      made fast reaching movements to a briefly presented stationary target, their hand
      shifted in a direction consistent with the motion of a distant and unrelated
      stimulus, a result contrary to most other findings. This can be seen early in the
      hand's trajectory (approximately 120 ms) and occurs continuously from programming
      of the movement through to its execution. The visuomotor system might make use of
      the motion signals arising from eye and head movements to update the positions of
      targets rapidly and redirect the hand to compensate for body movements.

PMID- 12815433
TI  - Abundant gene conversion between arms of palindromes in human and ape Y
      chromosomes.
AB  - Eight palindromes comprise one-quarter of the euchromatic DNA of the male
      specific region of the human Y chromosome, the MSY. They contain many testis
      specific genes and typically exhibit 99.97% intra-palindromic (arm-to-arm)
      sequence identity. This high degree of identity could be interpreted as evidence
      that the palindromes arose through duplication events that occurred about 100,000
      years ago. Using comparative sequencing in great apes, we demonstrate here that
      at least six of these MSY palindromes predate the divergence of the human and
      chimpanzee lineages, which occurred about 5 million years ago. The arms of these
      palindromes must have subsequently engaged in gene conversion, driving the paired
      arms to evolve in concert. Indeed, analysis of MSY palindrome sequence variation
      in existing human populations provides evidence of recurrent arm-to-arm gene
      conversion in our species. We conclude that during recent evolution, an average
      of approximately 600 nucleotides per newborn male have undergone Y-Y gene
      conversion, which has had an important role in the evolution of multi-copy testis
      gene families in the MSY.

PMID- 12815434
TI  - Fibronectin requirement in branching morphogenesis.
AB  - Many organs, including salivary glands, lung and kidney, are formed during
      embryonic development by epithelial branching. In branching morphogenesis,
      repetitive epithelial cleft and bud formation create the complex three
      dimensional branching structures characteristic of many organs. Although the
      mechanisms are poorly understood, one might involve the site-specific
      accumulation of some regulatory protein. Here we show that the extracellular
      matrix protein fibronectin is essential for cleft formation during the initiation
      of epithelial branching. Fibronectin messenger RNA and fibrils appeared
      transiently and focally in forming cleft regions of submandibular salivary-gland
      epithelia, accompanied by an adjacent loss of cadherin localization. Decreasing
      the fibronectin concentration by using small interfering RNA and inhibition by
      anti-fibronectin or anti-integrin antibodies blocked cleft formation and
      branching. Exogenous fibronectin accelerated cleft formation and branching.
      Similar effects of fibronectin suppression and augmentation were observed in
      developing lung and kidney. Mechanistic studies revealed that fibrillar
      fibronectin can induce cell-matrix adhesions on cultured human salivary
      epithelial cells with a local loss of cadherins at cell-cell junctions. Thus,
      fibronectin expression is required for cleft formation in branching morphogenesis
      associated with the conversion of cell-cell adhesions to cell-matrix adhesions.

PMID- 12815435
TI  - Regulation of flowering time by light quality.
AB  - The transition to flowering in plants is regulated by environmental factors such
      as temperature and light. Plants grown under dense canopies or at high density
      perceive a decrease in the ratio of red to far-red incoming light. This change in
      light quality serves as a warning of competition, triggering a series of
      responses known collectively as the 'shade-avoidance syndrome'. During shade
      avoidance, stems elongate at the expense of leaf expansion, and flowering is
      accelerated. Of the five phytochromes-a family of red/far-red light
      photoreceptors-in Arabidopsis, phytochrome B (phyB) has the most significant role
      in shade-avoidance responses, but the mechanisms by which phyB regulates
      flowering in response to altered ratios of red to far-red light are largely
      unknown. Here we identify PFT1 (PHYTOCHROME AND FLOWERING TIME 1), a nuclear
      protein that acts in a phyB pathway and induces flowering in response to
      suboptimal light conditions. PFT1 functions downstream of phyB to regulate the
      expression of FLOWERING LOCUS T (FT), providing evidence for the existence of a
      light-quality pathway that regulates flowering time in plants.

PMID- 12815436
TI  - CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication
      licensing.
AB  - To maintain genome stability, DNA replication is strictly regulated to occur only
      once per cell cycle. In eukaryotes, the presence of 'licensing proteins' at
      replication origins during the G1 cell-cycle phase allows the formation of the
      pre-replicative complex. The removal of licensing proteins from chromatin during
      the S phase ensures that origins fire only once per cell cycle. Here we show that
      the CUL-4 ubiquitin ligase temporally restricts DNA-replication licensing in
      Caenorhabditis elegans. Inactivation of CUL-4 causes massive DNA re-replication,
      producing cells with up to 100C DNA content. The C. elegans orthologue of the
      replication-licensing factor Cdt1 (refs 2, 3) is required for DNA replication. C.
      elegans CDT-1 is present in G1-phase nuclei but disappears as cells enter S
      phase. In cells lacking CUL-4, CDT-1 levels fail to decrease during S phase and
      instead remain constant in the re-replicating cells. Removal of one genomic copy
      of cdt-1 suppresses the cul-4 re-replication phenotype. We propose that CUL-4
      prevents aberrant re-initiation of DNA replication, at least in part, by
      facilitating the degradation of CDT-1.

PMID- 12815437
TI  - RecBCD enzyme is a DNA helicase with fast and slow motors of opposite polarity.
AB  - Helicases are molecular motors that move along and unwind double-stranded nucleic
      acids. RecBCD enzyme is a complex helicase and nuclease, essential for the major
      pathway of homologous recombination and DNA repair in Escherichia coli. It has
      sets of helicase motifs in both RecB and RecD, two of its three subunits. This
      rapid, highly processive enzyme unwinds DNA in an unusual manner: the 5'-ended
      strand forms a long single-stranded tail, whereas the 3'-ended strand forms an
      ever-growing single-stranded loop and short single-stranded tail. Here we show by
      electron microscopy of individual molecules that RecD is a fast helicase acting
      on the 5'-ended strand and RecB is a slow helicase acting on the 3'-ended strand
      on which the single-stranded loop accumulates. Mutational inactivation of the
      helicase domain in RecB or in RecD, or removal of the RecD subunit, altered the
      rates of unwinding or the types of structure produced, or both. This dual
      helicase mechanism explains how the looped recombination intermediates are
      generated and may serve as a general model for highly processive travelling
      machines with two active motors, such as other helicases and kinesins.

PMID- 12815438
TI  - RecBCD enzyme is a bipolar DNA helicase.
AB  - Escherichia coli RecBCD is a heterotrimeric helicase/nuclease that catalyses a
      complex reaction in which double-strand breaks in DNA are processed for repair by
      homologous recombination. For some time it has been clear that the RecB subunit
      possesses a 3' --> 5' DNA helicase activity, which was thought to drive DNA
      translocation and unwinding in the RecBCD holoenzyme. Here we show that purified
      RecD protein is also a DNA helicase, but one that possesses a 5' --> 3' polarity.
      We also show that the RecB and RecD helicases are both active in intact RecBCD,
      because the enzyme remains capable of processive DNA unwinding when either of
      these subunits is inactivated by mutation. These findings point to a bipolar
      translocation model for RecBCD in which the two DNA helicases are complementary,
      travelling with opposite polarities, but in the same direction, on each strand of
      the antiparallel DNA duplex. This bipolar motor organization helps to explain
      various biochemical properties of RecBCD, notably its exceptionally high speed
      and processivity, and offers a mechanistic insight into aspects of RecBCD
      function.

PMID- 12815439
TI  - Career-change carousel.

PMID- 12815440
TI  - Home truths.

PMID- 12815448
TI  - Effective number of breeders and maintenance of genetic diversity in the captive
      bearded vulture population.
AB  - We combined pedigree data with data derived from 14 microsatellite loci to
      investigate genetic diversity and its maintenance in the captive source
      population for the reintroduction of the bearded vulture into the Alps. We found
      the captive population to be genetically more variable than the largest natural
      population in Europe, both in terms of mean number of alleles per locus and mean
      observed and expected heterozygosity. Allelic diversity of the captive population
      was higher than, and mean heterozygosity measurements were comparable with the
      ones found in two large, extinct populations from Sardinia and the Alps
      represented by museum specimens. The amount of genetic variability recruited with
      the founders was still present in the captive population of the year 2000, mainly
      because the carriers of rare alleles were still alive. However, the decline in
      expected heterozygosity and the loss of alleles over generations in captivity was
      significant. Point estimates of effective population size, N(e), based on
      pedigree data and estimates of effective number of breeders, N(b), based on
      allele frequency changes, ranged from 20 to 30 and were significantly smaller
      than the census size. The results demonstrate that the amount of genetic
      variability in the captive bearded vulture population is comparable or even
      larger than the amount present in natural populations. However, the population is
      in danger to lose genetic variability over time because of genetic drift.
      Management strategies should therefore aim at preserving genetic variability by
      minimising kinship, and at increasing N(e) by recruiting additional founders and
      enhancing gene flow between the released, the captive and natural populations.

PMID- 12815449
TI  - Lack of response to selection for lower fluctuating asymmetry of mutant eyespots
      in the butterfly Bicyclus anynana.
AB  - Fluctuating asymmetry (FA) is claimed both to provide a means of evaluating
      developmental stability, and to reflect an individual's quality or the stress
      experienced during development. FA refers to the nondirectional variation between
      left and right sides, whereas directional asymmetry (DA) refers to a significant
      directional variation between the sides. We studied four eyespots on the dorsal
      forewing of the tropical butterfly, Bicyclus anynana. Two of the eyespots were
      specified by a mutant allele, Spotty, that was fixed in the stock. These eyespots
      showed higher FA than the two flanking, wild-type eyespots, although they are all
      formed by the same developmental pathway. We applied artificial selection for
      lower FA of the novel eyespots in an attempt to increase their developmental
      stability. There was significant variation present in individual FA in our study.
      However, this did not change as a result of the artificial selection. Most of the
      variation in FA can be accounted for by individual differences in developmental
      stability rather than by the applied selection or by environmental variation.
      Thus, it was not possible to produce any increased developmental stability of the
      novel eyespots by selecting for low FA. The estimates of realized heritability
      for both FA and DA of each eyespot were not significantly different from zero.
      The results suggest that FA provides little, if any, potential for exploring the
      mechanistic basis of developmental stability.

PMID- 12815450
TI  - Drosophila melanogaster and D. simulans rescue strains produce fit offspring,
      despite divergent centromere-specific histone alleles.
AB  - The interaction between rapidly evolving centromere sequences and conserved
      kinetochore machinery appears to be mediated by centromere-binding proteins. A
      recent theory proposes that the independent evolution of centromere-binding
      proteins in isolated populations may be a universal cause of speciation among
      eukaryotes. In Drosophila the centromere-specific histone, Cid (centromere
      identifier), shows extensive sequence divergence between D. melanogaster and the
      D. simulans clade, indicating that centromere machinery incompatibilities may
      indeed be involved in reproductive isolation and speciation. However, it is
      presently unclear whether the adaptive evolution of Cid was a cause of the
      divergence between these species, or merely a product of postspeciation
      adaptation in the separate lineages. Furthermore, the extent to which divergent
      centromere identifier proteins provide a barrier to reproduction remains unknown.
      Interestingly, a small number of rescue lines from both D. melanogaster and D.
      simulans can restore hybrid fitness. Through comparisons of cid sequence between
      nonrescue and rescue strains, we show that cid is not involved in restoring
      hybrid viability or female fertility. Further, we demonstrate that divergent cid
      alleles are not sufficient to cause inviability or female sterility in hybrid
      crosses. Our data do not dispute the rapid divergence of cid or the coevolution
      of centromeric components in Drosophila; however, they do suggest that cid
      underwent adaptive evolution after D. melanogaster and D. simulans diverged and,
      consequently, is not a speciation gene.

PMID- 12815451
TI  - Heterosis for biomass yield and related traits in five hybrids of Arabidopsis
      thaliana L. Heynh.
AB  - Heterosis is of utmost economic importance in plant breeding. However, its
      underlying molecular causes are still unknown. Given the numerous advantages of
      Arabidopsis thaliana as a model species in plant genetics and genomics, we
      assessed the extent of heterosis in this species using five hybrids derived from
      five ecotypes. Parents, F(1) and F(2), generations in both reciprocal forms were
      grown in a greenhouse experiment with four replications. Mid-parent heterosis
      (MPH) and best-parent heterosis (BPH) averaged across hybrids were surprisingly
      high for biomass yield (MPH: 60.3%; BPH: 32.9%) and rosette diameter (MPH: 49.4%;
      BPH: 34.8%), but smaller for flowering date (MPH: 27.5%; BPH: 18.5%), seed yield
      (MPH: 18.9%; BPH: 1.7%), and yield components. Individual hybrids varied
      considerably in their MPH and BPH values for all traits, one cross displaying
      140.1% MPH for biomass yield. MPH was not associated with parental genetic
      distance determined from molecular markers. Reciprocal effects were significant
      only in a few cases. With a proper choice of hybrids, our results encourage the
      use of Arabidopsis as a model species for investigating the molecular causes of
      heterosis.

PMID- 12815452
TI  - Admixture analysis of South Asian cattle.
AB  - We present population genetic analysis of microsatellite variation in seven Bos
      indicus cattle breeds from a variety of locations in South Asia. This is the
      first such study focusing within this area, which is one of the postulated
      centres of origin of domestic cattle. An estimate of the influence of Bos taurus
      ancestry was carried out using three approaches: by the systematic selection of
      population-associated alleles for B. taurus and examination of their frequency;
      by examining the truncation of genetic distances from European populations; and
      by a model-based Bayesian admixture analysis. These analyses revealed a B. taurus
      influence in the Indian subcontinent; part of a gradation which stretches from
      Europe through the Near East towards Indian and which may be of ancient origin.

PMID- 12815453
TI  - Chromosomal inversions effect body size and shape in different breeding resources
      in Drosophila buzzatii.
AB  - The cactophilic Drosophila buzzatii provides an excellent model for the study of
      reaction norms across discrete environments because it breeds on rotting tissues
      (rots) of very different cactus species. Here we test the possible effects of
      second chromosome inversions on body size and shape (wing loading) across
      suitable natural breeding substrates. Using homokaryotypic stocks derived from
      several lines homozygous for four naturally occurring chromosomal inversions, we
      show that arrangements significantly affect size-related traits and wing loading.
      In addition, karyotypes show differing effects, across natural breeding
      resources, for wing loading. The 2st and 2jz(3) arrangements decrease and the 2j
      arrangement increases wing loading. For thorax length and wing loading,
      karyotypic correlations across host plants are slightly lower in females than in
      males. These results support the hypothesis that these traits have a genetic
      basis associated with the inversion polymorphism.

PMID- 12815454
TI  - Associations between single nucleotide polymorphisms in candidate genes and
      growth rate in Arctic charr (Salvelinus alpinus L.).
AB  - We tested for associations between single nucleotide polymorphisms (SNPs) in five
      candidate genes allied with the growth hormone axis and the age-specific growth
      rate of Arctic charr (Salvelinus alpinus L.: Salmonidae). Two large full sib
      families (N=217 and 95) were created by backcrossing males that were hybrids
      between two phenotypically divergent populations from Labrador, Canada and from
      Nauyuk Lake, Canada to females that were from Nauyuk Lake. Measures of individual
      growth rate (wet weight and fork length) were made three times during a 420-day
      period after the juveniles were transferred from 4 to 11 degrees C. We then
      identified SNP markers in 10 proposed candidate genes known to be related to the
      growth hormone axis. Comparative alignments of amino-acid sequences and
      nucleotide sequences from other fish species were used to design PCR primers that
      would amplify 0.5-3 kb DNA regions of the candidate genes. All the individuals in
      the two backcross families were genotyped for these SNP markers using either
      polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or
      bidirectional amplification of specific alleles (Bi-PASA) approaches. A
      significant association between a particular SNP allele and early growth was
      found for the locus containing the growth hormone-releasing hormone and pituitary
      adenylate cyclase-activating polypeptide genes (GHRH/PACAP2, P=0.00001). We argue
      that using comparative sequence information to design PCR primers for candidate
      genes is an efficient method for locating quantitative triat loci in nonmodel
      organisms.

PMID- 12815455
TI  - Origin and colonization history of the white-clawed crayfish, Austropotamobius
      pallipes, in Ireland.
AB  - The presence of the white-clawed crayfish Austropotamobius pallipes complex in
      Ireland is suspected to be a result of human translocations. Two hypotheses have
      been formulated about the origin of the crayfish: from British populations or
      from western French populations. In order to resolve this question, nine Irish
      crayfish populations (a total of 124 individuals) were sampled along a south
      north cline and investigated by combining two molecular markers: mtDNA and RAPDs.
      The mtDNA marker, analysed by RFLP on the entire molecule, showed an absence of
      polymorphism within and among Irish populations. The RFLP haplotype found in
      Irish populations was only recorded in western French populations and was
      different from those found in English populations. This result may be explained
      by a human introduction of crayfish to Ireland from western French populations.
      RAPD analysis showed a clinal reduction of genetic variability within Irish
      populations from south to north, associated with an increase in their genetic
      differentiation. A stepwise model of translocation from the south to the north of
      Ireland is proposed and discussed.

PMID- 12815456
TI  - Genetic recombination and adaptation to fluctuating environments: selection for
      geotaxis in Drosophila melanogaster.
AB  - Heritable variation in fitness is the fuel of adaptive evolution, and sex can
      generate new adaptive combinations of alleles. If the generation of beneficial
      combinations drives the evolution of recombination, then the level of
      recombination should result in changes in the response to selection. Three types
      of lines of Drosophila melanogaster varying in their level of genetic
      recombination were selected over 38 generations for geotaxis. The within
      chromosome recombination level of these lines was controlled for 60% of the
      genome: chromosome X and chromosome II. The full recombination lines had normal,
      unmanipulated levels of recombination on these two chromosomes. Conversely,
      nonrecombination lines had recombination effectively eliminated within the X and
      second chromosomes. Finally, partial recombination lines had the effective rate
      of within-chromosome recombination lowered to 10% of natural levels for these two
      chromosomes. The rate of response to selection was measured for continuous
      negative geotaxis and for a fluctuating environment (alternating selection for
      negative and positive geotaxis). All selected Drosophila lines responded to
      selection and approximately 36% of the response to selection was because of the X
      and second chromosomes. However, recombination did not accelerate adaptation
      during either directional or fluctuating selection for geotaxis.

PMID- 12815457
TI  - Refinements to the partitioning of the inbred genotypic variance.
AB  - Natural gene flow is often localised because of gamete dispersal limitations, and
      the quantity and structure of the genotypic variance in such populations is a key
      to predicting the advance from selection, in both evolution and artificial
      breeding programmes. Earlier derivations of this variance have shown that the
      total dominance variance may increase with inbreeding despite the fact that
      heterozygosity is decreasing. This anomaly has been corrected following the de
      novo biometrical derivation presented in this paper. The whole population also
      subdivides into descendant lineages that differ in allele frequencies and means
      because of the dispersion caused by genetic drift and continuing localisation of
      gamodemes. The paper defines for the first time the among-line and within-line
      partitions of the dominance variance; and corrects anomalies in the total genic
      (additive genetic) variance, and its underlying inbred average alle-substitution
      effect. The revisions also clarify the connections between the Fisher-Falconer,
      Mather-Hayman, and Wright approaches to defining the inbred genotypic variance.
      Relationships are discussed between the population dispersion structure and
      genetic efficiency in selection.

PMID- 12815458
TI  - Nitric oxide signaling regulates mitochondrial number and function.

PMID- 12815459
TI  - Antiandrogen-induced cell death in LNCaP human prostate cancer cells.
AB  - Antiandrogens such as Casodex (Bicalutamide) are designed to treat advance stage
      prostate cancer by interfering with androgen receptor-mediated cell survival and
      by initiating cell death. Treatment of androgen sensitive, non-metastatic LNCaP
      human prostate cancer cells with 0-100 microM Casodex or 0-10 ng/ml TNF-alpha
      induces cell death in 20-60% of the cells by 48 h in a dose-dependent manner. In
      cells treated with TNF-alpha, this is accompanied by the loss of mitochondrial
      membrane potential (DeltaPsim) and cell adhesion. In contrast, cells treated with
      Casodex display loss of cell adhesion, but sustained mitochondrial dehydrogenase
      activity. Overexpression of Bcl-2 in LNCaP cells attenuates the induction of cell
      death by TNF-alpha but not Casodex, suggesting that mitochondria depolarization
      is not required for the induction of cell death by Casodex. While both TNF-alpha
      and Casodex-induced release of cytochrome c in LNCaP cell is predominantely
      associated with the translocation and cleavage of Bax, our data also suggest that
      Casodex induces cell death by acting on components downstream of decline of
      DeltaPsim and upstream of cytochrome c release. Furthermore, while induction of
      both caspase-3 and caspase-8 activities are observed in TNF-alpha and Casodex
      treated cells, a novel cleavage product of procaspase-8 is seen in Casodex
      treated cells. Taken together, these data support the hypothesis that Casodex
      induces cell death by a pathway that is independent of changes in DeltaPsim and
      Bcl-2 actions and results in an extended lag phase of cell survival that may
      promote the induction of an invasive phenotype after treatment.

PMID- 12815460
TI  - Protein phosphatase 2A-linked and -unlinked caspase-dependent pathways for
      downregulation of Akt kinase triggered by 4-hydroxynonenal.
AB  - We studied the signal pathways for regulation of serine/threonine protein kinase
      Akt in Jurkat cells that had been treated with 4-hydroxynonenal (HNE) for caspase
      dependent apoptosis induction. Treatment of cells with HNE led to a decrease in
      the level of Akt activity due to the dephosphorylation at Ser473, a major
      regulatory phosphorylation site. HNE-mediated dephosphorylation of Akt was
      prevented by a protein phosphatase 2A (PP2A) inhibitor, okadaic acid, and by a
      caspase-3 inhibitor, DEVD-CHO. HNE treatment resulted in an increase in the total
      level of PP2A activity, release of active tyrosine-dephosphorylated PP2A from the
      cytoskeleton and PP2A-Akt association, which were all dependent on caspase-3
      activation. These results suggest that the level of PP2A activity is at least in
      part determined by its tyrosine phosphorylation, which is dually controlled by
      okadaic acid-sensitive phosphatases and protein-tyrosine kinases. Possibly
      underlying the mechanism of caspase-mediated activation of PP2A, HNE treatment
      resulted in downregulation of the activity of Src kinase, as a representative
      caspase-sensitive kinase to phosphorylate PP2A at tyrosine. In addition,
      activated caspase-3 partially cleaved Akt at a late stage of the apoptosis. These
      results indicate the existence of two distinct caspase-dependent signal pathways
      for downregulation of Akt that works as a mechanism of positive feedback
      regulation for HNE-triggered apoptotic signals.

PMID- 12815461
TI  - Protein kinase C-mediated necrosis-apoptosis switch of cortical neurons by
      conditioned medium factors secreted under the serum-free stress.
AB  - Cortical neurons die in necrosis in the low-density (LD) culture, and in
      apoptosis in the high-density (HD) culture under the serum-free condition without
      any supplements. The neuronal death in LD culture was delayed by conditioned
      medium (CM) factors prepared from the HD culture. The CM switched the cell death
      mode from necrosis to apoptosis, characterized by various cell death markers and
      transmission electron microscopy. The CM inhibited the rapid decrease in cellular
      ATP levels and [3H]-2-deoxy glucose ([3H]-2-DG) uptake in the LD culture.
      Inhibitors of phospholipase C and protein kinase C effectively abolished the CM
      induced elevation of survival activity, [3H]-2-DG uptake and ATP levels, and
      necrosis-apoptosis switch. All these results suggest that CM caused the cell
      death mode switch from necrosis to apoptosis through phospholipase C- and protein
      kinase C-mediated mechanisms.

PMID- 12815462
TI  - Molecular evidence for the nuclear localization of FADD.
AB  - The Fas-associated death domain (FADD) adaptor protein FADD/Mort-1 is recruited
      by several members of the tumor necrosis factor receptor (TNFR) superfamily
      during cell death activated via death receptors. Since most studies have focused
      on the interaction of FADD with plasma membrane proteins, FADD's subcellular
      location is thought to be confined to the cytoplasm. In this report, we show for
      the first time that FADD is present in both the cytoplasm and the nucleus of
      cells, and that its nuclear localization relies on strong nuclear localization
      and nuclear export signals (NLS and NES, respectively) that reside in the death
      effector domain (DED) of the protein. Specifically, we found that a conserved
      basic KRK35 sequence of the human protein is necessary for FADD's nuclear
      localization, since disruption of this motif leads to the confinement of FADD in
      the cytoplasm. Furthermore, we show that the leucine-rich motif LTELKFLCL28 in
      the DED is necessary for FADD's nuclear export. Functionally, mutation of the NES
      of FADD and its seclusion in the nucleus reduces the cell death-inducing efficacy
      of FADD reconstituted in FADD-deficient T cells.

PMID- 12815463
TI  - HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase
      independent autophagic cell death.
AB  - The Drosophila spinster (spin) gene product is required for programmed cell death
      in the nervous and reproductive systems. We have identified a human homologue of
      the Drosophila spin gene product (HSpin1). HSpin1 bound to Bcl-2 and apoptosis
      regulator Bcl-X (Bcl-xL), but not to proapoptotic members such as Bcl-2
      associated X protein and Bcl-2 homologous antagonist killer, in cells treated
      with TNF-alpha. Exogenous expression of HSpin1 resulted in the cell death without
      inducing a release of cytochrome c from mitochondria. Overexpression of Bcl-xL
      inhibited the HSpin1-induced cell death. Interestingly, a necrosis inhibitor,
      pyrrolidine dithiocarbomate, but not the pancaspase inhibitors, carbobenzoxy-VAD
      fluoromethyl ketone and p35, blocked the HSpin1-induced cell death. HSpin1
      induced cell death increases autophagic vacuole and mature form of cathepsin D,
      suggesting a novel caspase-independent cell death, which is link to autophagy.

PMID- 12815464
TI  - Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin
      resistant testicular germ cell tumor cell line.
AB  - Testicular germ cell tumors (TGCTs) are unusually sensitive to cisplatin. In the
      present study the role of the CD95 death pathway in cisplatin sensitivity of TGCT
      cells was studied in Tera and its in vitro acquired cisplatin-resistant subclone
      Tera-CP. Cisplatin induced an increase in CD95 membrane expression, which
      preceded the onset of apoptosis. Cisplatin-induced apoptosis was efficiently
      blocked by caspase-8 inhibitor zIETD-fmk in Tera cells, but only partially in
      Tera-CP cells. In addition, cisplatin induced FADD and caspase-8 recruitment to
      the CD95 receptor in Tera cells, which was not noticed in Tera-CP cells.
      Moreover, overexpression of vFLIP reduced apoptosis induction by cisplatin in
      Tera cells. CD95L-blocking experiments revealed the involvement of CD95/CD95L
      interactions in cisplatin-induced apoptosis of Tera cells as well as cisplatin
      sensitive 833KE TGCT cells. Tera and 833KE cells, treated with low doses of
      cisplatin, were sensitive for an apoptosis-inducing anti-CD95 antibody. In
      contrast, CD95L blocking had no effect on cisplatin-induced apoptosis in Tera-CP
      or Scha, an intrinsic resistant TGCT cell line, nor did anti-CD95 antibody induce
      additional apoptosis in cisplatin-treated Tera-CP or Scha cells. Taken together,
      these results show that (1) cisplatin sensitivity of TGCT cells is dependent on
      the activation of the CD95 death pathway and (2) loss of cisplatin-induced
      activation of this CD95 signaling pathway may result in resistance to cisplatin.

PMID- 12815465
TI  - Hypoxia-induced cell death in human malignant glioma cells: energy deprivation
      promotes decoupling of mitochondrial cytochrome c release from caspase processing
      and necrotic cell death.
AB  - Hypoxia induces apoptosis in primary and transformed cells and in various tumor
      cell lines in vitro. In contrast, there is little apoptosis and predominant
      necrosis despite extensive hypoxia in human glioblastomas in vivo. We here
      characterize ultrastructural and biochemical features of cell death in LN-229, LN
      18 and U87MG malignant glioma cells in a paradigm of hypoxia with partial glucose
      deprivation in vitro. Electron microscopic analysis of hypoxia-challenged glioma
      cells demonstrated early stages of apoptosis but predominant necrosis. ATP levels
      declined during hypoxia, but recovered with re-exposure to normoxic conditions
      unless hypoxia exceeded 8 h. Longer hypoxic exposure resulted in irreversible ATP
      depletion and delayed cell death. Hypoxia induced mitochondrial release of
      cytochrome c, but there was no cleavage of caspases 3, 7, 8 or 9, and no DNA
      fragmentation. Ectopic expression of BCL-XL conferred protection from hypoxia
      induced cell death, whereas the overexpression of the antiapoptotic proteins X
      linked-inhibitor-of-apoptosis-protein and cytokine response modifier-A had no
      effect. These findings suggest that glioma cells resist adverse effects of
      hypoxia until energy stores are depleted and then undergo necrosis rather than
      apoptosis because of energy deprivation.

PMID- 12815466
TI  - Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells
      without affecting cell cycle progression and surface IgM expression.
AB  - The transmembrane receptor Notch1 plays a crucial role in differentiation and
      apoptosis of hematopoietic cells. To investigate the influence of Notch1 on
      apoptosis and cell growth of mature murine B cells, we transduced the murine B
      lymphoma line NYC 31.1 with a constitutively active, intracellular form of human
      Notch1 (Notch1-ICT). NYC cells represent mature activated B cells that can be
      induced to undergo apoptosis by crosslinking of the B-cell receptor (BCR). In
      contrast to investigations in immature chicken B-cell lines, transduced Notch1
      ICT did not affect cell cycle progression, cell growth or surface IgM levels in
      NYC cells and resulted only in a slight induction of apoptosis. However, BCR
      crosslinking enhanced apoptosis, but did not influence cell cycle progression in
      Notch1-ICT-positive NYC cells. These data imply a distinct function of Notch1 in
      mature murine B-cells as compared to immature chicken B cells and provide further
      evidence for Notch1's involvement in B-cell differentiation and development.

PMID- 12815467
TI  - Caspase inhibition prevents the mitochondrial release of apoptosis-inducing
      factor.

PMID- 12815468
TI  - Terminal differentiation of human epidermal keratinocytes involves mitochondria-
      and caspase-dependent cell death pathway.

PMID- 12815469
TI  - A new quantitative assay for cytochrome c release in apoptotic cells.

PMID- 12815470
TI  - Fenretinide induces cytochrome c release, caspase 9 activation and apoptosis in
      the absence of mitochondrial membrane depolarisation.

PMID- 12815471
TI  - Hematopoietic stem cell gene therapy: progress toward therapeutic targets.
AB  - The concept of hematopoietic stem cell gene therapy is as exciting as that of
      stem cell transplantation itself. The past 20 years of research have led to
      improved techniques for transferring and expressing genes in hematopoietic stem
      cells and preclinical models now routinely indicate the ease with which new genes
      can be expressed in repopulating stem cells of multiple species. Both modified
      murine oncoretroviruses and lentiviruses transmit genes into the genome of
      hematopoietic stem cells and allow expression in the host following
      transplantation. Using oncoretroviruses, therapeutic genes for severe combined
      immunodeficiency, common variable gamma chain immunodeficiency, chronic
      granulomatous disease, Hurler's and Gaucher's Disease have all been used
      clinically with only modest success except for the patients with immunodeficiency
      in whom a partial T-cell chimerism has been dramatic. Since stem cell selection
      in vivo appears important to the therapeutic success of gene transfer, drug
      resistance selection, most recently using the MGMT gene, has been developed and
      appears to be safe. Future trials combining a drug resistance and therapeutic
      gene are planned, as are trials using safety-modified lentiviruses. The
      therapeutic potential of hematopoietic stem cell gene therapy, particularly given
      recent advances in stem cell plasticity, remains an exceptionally exciting area
      of clinical research.

PMID- 12815472
TI  - Safety and outcome after fludarabine-thiotepa-TBI conditioning for allogeneic
      transplantation: a prospective study of 30 patients with hematologic
      malignancies.
AB  - Fludarabine, thiotepa and total body irradiation (TBI) has been used as
      conditioning in haplo-identical transplantation. We studied this conditioning
      regimen in adults undergoing matched sibling transplantation and alternative
      donor transplantation. A total of 30 consecutive patients underwent matched
      related, haplo-identical related or matched unrelated donor transplantation with
      fludarabine, thiotepa and TBI conditioning. All but four had advanced hematologic
      malignancies. For haplo-identical transplant, ATG was added to the regimen. All
      patients received peripheral blood stem cells; these were T-cell depleted for 2
      antigen or 3-antigen mismatched related transplantation. Additional graft-versus
      host disease prophylaxis consisted of tacrolimus and mini-methotrexate. One
      recipient of haplo-identical transplant failed to engraft; all other evaluable
      patients had prompt engraftment. Four patients died of regimen-related toxicity.
      In all, 14 additional patients died of regimen-related causes including four from
      failure to thrive with persistent thrombocytopenia and four from delayed
      pulmonary toxicity. Six patients relapsed. Progression-free survival at 12 months
      was 47% (90% CI: 25-69%) for recipients of HLA-identical sibling transplants and
      30% (90% CI: 14-46%) for all patients. Five of six long-term survivors have
      extensive chronic GVHD. As a result of the delayed complications and a relatively
      high recurrence rate, we abandoned this regimen.

PMID- 12815473
TI  - Towards a myeloablative regimen with clinical potential: I. Treosulfan
      conditioning and bone marrow transplantation allow induction of donor-specific
      tolerance for skin grafts across full MHC barriers.
AB  - To investigate whether we could create a radiation-free conditioning regimen to
      induce permanent mixed and multilineage chimerism and donor-specific tolerance,
      we treated recipient mice with anti-T-cell antibodies, varying and fractionated
      doses of Treosulfan and fully MHC disparate bone marrow cells. Treosulfan is
      mainly used in the treatment of ovarian cancer. It is a structural analog of
      busulfan, but it does not induce severe hepatotoxicity or veno-occlusive disease
      at or above the maximum tolerated dose, lacks significant nonhematological
      toxicity and has limited organ toxicity. We report here the successful induction
      of permanent mixed multilineage chimerism and donor-specific tolerance as was
      proven by skin transplantation and IFN-gamma ELISPOT. In conclusion, because of
      its lower nonhematological toxicity, compared with other myeloablative regimens
      (eg irradiation or busulfan admin- istration), Treosulfan could be a better
      candidate for conditioning to induce donor-specific allograft tolerance.

PMID- 12815474
TI  - Early lymphocyte recovery is an important determinant of outcome following
      allogeneic transplantation with CD34+ selected graft and limited T-cell addback.
AB  - We evaluated the outcome of 29 patients (age 22-60 years), who received a
      CD34+selected related (n=16) or unrelated graft (n=13) with limited T-cell
      addback (TCAB) (median 5.9 x 10(4)/kg) following full-intensity conditioning for
      haematological malignancies. In all, 16 patients (55%) had either advanced
      disease or previous transplants. The cumulative incidences of grade 2-4 acute
      GVHD were 15.4 and 19.2% and that for chronic extensive GVHD were 35 and 37% in
      related and unrelated graft recipients, respectively. The strongest predictor of
      nonrelapse mortality and overall survival was the absolute lymphocyte count (ALC)
      at 30 days; patients with ALC<0.35 x 10(9)/l having an NRM and OS of 59.2 and
      24.7%, compared to 10 and 90% in those with a higher ALC. Patients with acute
      leukaemia had poorer survival and this was associated with a lower ALC as well.
      Thus, TCAB with a CD34+ selected graft resulted in a comparable outcome in both
      older and younger patients, but the survival was strongly influenced by early
      lymphocyte recovery.

PMID- 12815475
TI  - Tetraploid myeloid cells in donors of peripheral blood stem cells treated with
      rhG-CSF.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is frequently
      used to mobilize CD34+ cells in healthy donors and patient with malignant
      diseases prior to peripheral blood stem cell (PBSC) harvest. To analyze the
      effects of rhG-CSF on morphology and genotype of white blood cells, a novel
      multiparametric cell scanning system that combines morphologic, immune and
      genotypic analyses of the same cells was used. We report here that tetraploid
      myeloid cells are present in the peripheral blood of donors treated with rhG-CSF.
      The tetraploidy was detected in up to 0.6% of differentiated myeloid cells and
      all observed CD34+ cells were diploid. Thus, short treatment with rhG-CSF of PBSC
      donors induces numerfical chromosomal alterations in a small subset of mature
      myeloid cells.

PMID- 12815476
TI  - Stem cell transplantation for myelofibrosis: a report from two Canadian centers.
AB  - We describe the course of 25 patients with myelofibrosis (MF) due to agnogenic
      myeloid metaplasia (n=19) or essential thrombocytosis (n=6) who underwent
      allogeneic stem cell transplantation (SCT) at one of two Canadian centers. The
      median age at transplantation was 48.7 (IQR 45.9-50.4) years and transplantation
      was carried out at a median of 10.7 (IQR 5.67-26.5) months after diagnosis.
      Granulocyte engraftment (absolute neutrophil count >0.5 x 109/l) occurred at a
      median of 20 days after transplantation for splenectomized patients, compared
      with 27.5 days for nonsplenectomized individuals (P=0.03). Increased risk of
      grade II-IV acute graft-versus-host disease (P=0.04) was noted in patients
      transplanted after splenectomy. Patients with MF received 0.264+/-0.189 U of
      packed red blood cells per day over the first 180 days after transplantation, and
      remained dependent on red blood cell transfusions for a median of 123 (IQR 48
      205) days. Complete remission of MF was documented in 33% of evaluable patients.
      The 1 year cumulative nonrelapse mortality was 48.3%. Median survival for this
      group of patients was 393 (IQR 109-1014+) days, with a projected 2-year overall
      survival of 41%. We conclude that allogeneic SCT offers a reasonable chance for
      prolonged survival in patients with advanced MF, but this occurs at the cost of
      considerable toxicity and nonrelapse mortality.

PMID- 12815477
TI  - Oestrogen receptor alpha gene polymorphism associates with occurrence of graft
      versus-host disease and reduced survival in HLA-matched sib-allo BMT.
AB  - Oestrogen receptors mediate the cellular response to oestrogens and related
      compounds and promote a wide range of effects on haemopoiesis. Polymorphisms of
      the oestrogen receptor genes have previously been associated with variation in
      bone mineral density, likelihood of fractures, risk of developing Alzheimer's
      disease, endometrial cancer and response to hormone replacement therapy. We
      examined the polymorphisms in both ERalpha and ERbeta genes in 108 patients
      receiving a bone marrow transplant from an HLA-matched sibling donor, and
      compared ER genotype with outcomes of occurrence of graft-versus-host disease
      (GVHD) and survival using logistic regression analysis. Polymorphism of ERalpha
      (presence of the PX haplotype (PvuII-XbaI RFLP) of intron 1), but not ERbeta, in
      the patient genotype associates with occurrence of acute GVHD and with lower
      overall survival, following correction for known clinical and genotypic risk
      features. Analysis of ER genotype prior to transplant might therefore inform on a
      patient's likelihood of developing post-transplant complications. Variation in
      transplant performance because of ER genotype suggests an underlying role for
      oestrogens in the pathophysiology of transplant-related complications, and
      suggests that oestrogen-related therapy may offer a new modality of post
      transplant support.

PMID- 12815478
TI  - Enhanced antileukemic activity of allogeneic peripheral blood progenitor cell
      transplants following donor treatment with the combination of granulocyte colony
      stimulating factor (G-CSF) and stem cell factor (SCF) in a murine transplantation
      model.
AB  - Allogeneic peripheral blood progenitor cells (PBPCs) have mostly been mobilized
      by granulocyte colony-stimulating factor (G-CSF). There is neither clinical nor
      experimental data available addressing the question if other hematopoietic growth
      factors or combinations thereof might influence engraftment, graft-versus-host
      disease (GvHD), and graft-versus-leukemia (GvL) effects after allogeneic
      peripheral blood progenitor cell transplantation (PBPCT). We used a murine model
      to investigate these parameters after transplantation of PBPCs mobilized with G
      CSF and SCF either alone or in combination. Treatment of splenectomized DBA and
      Balb/c mice with 250 microg/kg/day G-CSF for 5 days resulted in an increase of
      CFU-gm from 0 to 53/microl. The highest progenitor cell numbers (147/microl) were
      observed after treatment with 100 microg/kg/day SCF administered in conjunction
      with G-SCF. No differences were detected with regard to the number of T cells
      (CD3+), T cell subsets (CD4+, CD8+), B cells (CD19+) and NK cells (NK1.1+) in
      PBPC grafts mobilized by G-CSF plus SCF compared to those mobilized with G-CSF
      alone. The antileukemic activity of syngeneic and MHC-identical allogeneic PBPC
      grafts was investigated in lethally irradiated Balb/c mice bearing the B
      lymphatic leukemia cell line A20. In this model, PBPCs mobilized by G-CSF plus
      SCF exerted a significantly higher antileukemic activity compared to grafts
      mobilized by G-CSF alone (94 vs 71% freedom from leukemia at day 100, P<0.05).
      The antileukemic effect was lowest after BMT (38% freedom from leukemia). Since
      significant differences in the incidence of lethal GvHD were not observed,
      improved GVL-activity resulted in superior overall survival. Our data demonstrate
      that the utilization of specific hematopoietic growth factors not only improve
      the yield of hematopoietic progenitor cells but can also significantly enhance
      the immunotherapeutic potential of allografts.

PMID- 12815479
TI  - Quantitative molecular evaluation in autotransplant programs for follicular
      lymphoma: efficacy of in vivo purging by Rituximab.
AB  - The main aim of this paper was to compare results of Genescan and real-time PCR
      methods in order to detect contamination in harvests from patients with
      follicular lymphoma. The secondary goal was to evaluate the efficacy of Rituximab
      as an in vivo purging agent. A total of 23 patients had been treated with CHOP
      followed by either high-dose therapy (12 patients) or high-dose plus Rituximab
      (11 patients), both followed by autologous transplantation. Results show that 86%
      of harvests from patients treated with Rituximab were PCR-negative compared to
      14.3% from controls. Real-time PCR was more sensitive than Genescan PCR;
      quantitative analysis revealed a correlation between the amount of contamination
      in the harvests and relapse after transplantation. Whereas all patients reinfused
      with negative aphereses achieved complete remission and showed a significantly
      better 5-year PFS (100%) compared to those reinfused with contaminated samples
      (41%), a very low amount of contamination does not appear to negatively affect
      outcome, suggesting that determination of a cutoff in the contamination level of
      harvests could be useful. Results suggest that real-time PCR is superior to
      Genescan PCR to select transplantable harvests and confirm the ability of
      Rituximab as an in vivo purging tool for follicular lymphoma.

PMID- 12815480
TI  - A comparison of T-, B- and NK-cell reconstitution following conventional or
      nonmyeloablative conditioning and transplantation with bone marrow or peripheral
      blood stem cells from human leucocyte antigen identical sibling donors.
AB  - This retrospective study compares the reconstitution of T, B and NK cells in
      three groups of patients transplanted for haematological malignancies with grafts
      from their HLA-identical sibling donors. In all, 15 patients received PBSC after
      a nonmyeloablative conditioning regimen consisting of fludarabine and 200 cGy
      TBI, 13 patients received PBSC after myeloablative conditioning and 37 patients
      received BM after myeloablative conditioning. In the nonmyeloablative group, the
      NK cells normalised after 1 month, the CD8+ T cells normalised after 3 months,
      the CD4+ T cells reached near normal values after 9 months and the B cell values
      were reduced until 12 months after transplant. In the two myeloablative groups,
      recipients of PBSC had a significantly higher number of CD4+ T cells after 4
      months (P=0.004) and after 12 months (P=0.001), than recipients of BM. We found
      no differences in the T cell reconstitution between the two PBSC groups. This was
      of interest as the recipients of nonmyeloablative conditioning were older
      (P<0.001) and had a higher occurrence of chronic GVHD (P<0.05) than the
      recipients of myeloablative conditioning. In contrast, the recipients of
      nonmyeloablative conditioning had a delayed B cell recovery when compared to the
      patients who received myeloablative conditioning (P=0.04).

PMID- 12815481
TI  - Respiratory viral infections after bone marrow/peripheral stem-cell
      transplantation: the Christie hospital experience.
AB  - Respiratory virus infections are an important cause of morbidity and mortality in
      bone marrow transplant patients. A retrospective study was performed on the bone
      marrow transplant unit at the Christie Hospital Manchester. The aim of this study
      was to determine the frequency, clinical presentation, laboratory diagnosis,
      types of intervention (eg antiviral agents used) and the outcome of such
      infections in this cohort of transplant recipients. Data were collected from a
      total of 626 adult patients and showed 27 patients with 29 confirmed episodes of
      viral respiratory tract infections. The viruses present were rhinovirus (40%),
      respiratory syncytial virus (RSV) (22.2%), influenza A (18.5%), parainfluenza
      (PIV) (14.8%) and enteroviruses (7.4%). The overall frequency of documented
      respiratory virus infections was 4.3% during the 5-year period of the study. The
      prevalence of respiratory viral infections was 7.8% among allogeneic and 2.3%
      among autologous transplant recipients. The frequency of lower respiratory tract
      infection (LRTI) was 3.0% among allogeneic and 1.3% among autologous transplant
      recipients. Eight patients died (seven had allogeneic transplants). Three of
      these deaths were directly attributable to a respiratory viral infection (two
      rhinoviruses; one PIV 3). This study further supports the role played by human
      respiratory viruses in transplant-associated morbidity and mortality, and
      particularly highlights the significance of rhinovirus infections.

PMID- 12815482
TI  - Incidence, survival and risk factors for the development of veno-occlusive
      disease in pediatric hematopoietic stem cell transplant recipients.
AB  - The incidence, risk factors and mortality of veno-occlusive disease (VOD) were
      identified for 142 pediatric hematopoietic stem cell (HSC) transplant recipients
      with hematological malignancies (83), solid tumors (41) and nonmalignant diseases
      (18). This historical cohort of 142 HSC transplant patients, from January 1993
      through June 2000, was assessed by chart review. Risk factors for the development
      of VOD and mortality were assessed by multiple logistic regression and Kaplan
      Meier survival curves respectively. The incidence of VOD was 18.3% (26/142
      transplants). Multivariate analysis reconfirmed the known pretransplant risk
      factors of induction therapy with busulfan and transplantation with matched
      unrelated donor cells as significant risk factors for the development of VOD. In
      addition, two new risk factors, positive CMV serology in the recipient and TPN
      provided in the 30 days prior to transplant, were identified. Mortality in
      transplant patients at 100 days was greater in the VOD-positive group (10/26
      (38.5%)) compared to the VOD-negative group (11/116 (9.5%) (P=0.001)). The risk
      of death was 4.97 times higher with 95% CIs (2.11, 11.71) for the VOD-positive
      group. Decreasing the risk factors for VOD may decrease mortality in this patient
      population.

PMID- 12815483
TI  - Autoimmune thrombocytopenic purpura after autologous stem cell transplantation.
AB  - The pathogenesis of thrombocytopenia occurring after autologous stem cell
      transplantation (ASCT) remains unclear. Six cases of classical peripheral
      thrombocytopenia that developed after ASCT for non-Hodgkin's lymphoma (NHL) are
      presented. Resolution of this complication was obtained by usual treatment such
      as steroids, splenectomy or progressively resolved without specific treatment.
      Five out of six patients have been followed for more than 5 years after
      hematopoietic transplantation and are still alive in complete remission despite
      poor prognostic factors at diagnosis. Several arguments suggest that this
      phenomenon represents autoimmune thrombocytopenia and may be the consequence of
      an altered immune balance. Consequently, development of autoimmune reactions
      after bone marrow transplantation might be associated with an antitumoral effect
      (graft-versus-lymphoma effect).

PMID- 12815484
TI  - High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem
      cell transplantation as a consequence of intensive immunosuppressive treatment.
AB  - The occurrence of post-transplant lymphoproliferative disorder (PTLD) in relation
      to immunosuppressive treatment was determined in 257 patients treated with non-T
      cell-depleted allogeneic stem cell transplantation from an HLA-matched sibling
      (173 patients) or unrelated donor (84 patients). The conditioning consisted of
      total body irradiation and cyclophosphamide (myeloablative conditioning, 250
      patients), or fludarabine combined with cyclophosphamide or a single 2 Gy dose of
      TBI (nonmyeloablative conditioning, seven patients). In transplantations from an
      unrelated donor, the patients also received antithymocyte globulin (ATG). The
      prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine A,
      methotrexate, and methylprednisolone. The autopsy reports of deceased patients
      were systematically reviewed, and the autopsy materials of cases suggestive of
      PTLD were re-examined histologically for Epstein-Barr virus (EBV). Nineteen
      patients with EBV-positive PTLD were identified, of whom six had been
      transplanted from a sibling donor and 13 from an unrelated donor. All the
      patients who developed PTLD had been given ATG either for the treatment of
      steroid-resistant acute GVHD (all PTLD patients with a sibling donor and one with
      an unrelated donor), or as part of the conditioning (all patients with an
      unrelated donor). In conclusion, in transplantations from an HLA-identical donor
      with a non-T-cell-depleted graft, the risk of PTLD correlated strongly with the
      intensity of the immunosuppressive treatment.

PMID- 12815485
TI  - Graft-versus-tumor effect in a patient with advanced neuroblastoma who received
      HLA haplo-identical bone marrow transplantation.
AB  - A 5-year-old boy received CD34-positive HLA haplo-identical bone marrow
      transplantation from his father as treatment for refractory advanced
      neuroblastoma. He had residual disease in the para-aortic lymph nodes and
      multiple bones after the transplant. However, all of his residual disease had
      disappeared completely 3 years later. He developed grade I acute graft-versus
      host disease (GVHD) but had no symptoms of chronic GVHD or any other
      complications. This case demonstrates the possibility of a graft-versus-tumor
      effect against neuroblastoma by HLA-mismatched allogeneic hematopoietic stem cell
      transplantation.

PMID- 12815486
TI  - Complete resolution of severe chronic active Epstein-Barr virus infection by
      cultured, activated donor T lymphocyte infusion after nonmyeloablative stem cells
      allografting.
AB  - A patient with chronic active Epstein-Barr virus (EBV) infection was treated by
      allogeneic SCT from an HLA-identical sibling donor, using a nonmyeloablative
      regimen. Even on day 70, mixed chimerism remained together with a quite high
      viral load. On days 76 and 90, donor lymphocytes were infused after short-term
      culture with OKT3 plus recombinant IL-2. At 8 days after the last dose, all
      hematopoietic cells were shown to be donor-type dominant; thereafter, the viral
      load started to decrease and finally disappeared. Anti-mHA-specific CTLs were
      generated in vitro, which were shown to be effective in eradicate viral-infected
      recipient T lymphocytes.

PMID- 12815487
TI  - Rapid engraftment of mast cells of donor origin in a case of acute myeloid
      leukemia with mast cell leukemia after allogeneic stem cell transplantation.
AB  - Mastocytosis is a rare disease characterized by an abnormal increase of mast
      cells in tissues. We report a case of acute myeloid leukemia (AML) with t(8;21)
      and mast cell leukemia (MCL) in which the mastocytosis persisted after standard
      chemotherapy and allogeneic stem cell transplantation, although the myeloid
      leukemia achieved molecular complete remission soon after induction chemotherapy.
      Donor-type mast cells were noted on d31 after transplant. No c-kit mutation was
      found before or after the transplant. This represents the first reported case in
      which rapid engraftment of mast cells of donor origin was documented. Thus, the
      possibility that the mast cell originates from a common myeloid precursor cell
      may be questioned and a reactive process should be considered in some cases of
      systemic mastocytosis.

PMID- 12815488
TI  - Strongyloidiasis pre and post autologous peripheral blood stem cell
      transplantation.
AB  - Hyperinfection with strongyloides stercolis occurs in the setting of chronic
      strongyloides infection in conjunction with immune suppression. Although
      malnutrition remains the major secondary cause worldwide in the developed world,
      iatrogenic immune suppression is an important precipitant. Autologous stem cell
      transplantation recipients are significantly immunocompromised albeit
      temporarily. Despite the increasing use of haemopoetic stem cell transplantation,
      hyperinfection with strongyloides has rarely been reported. We describe two cases
      of patients transplanted with chronic strongyloidiasis. In one case eradication
      therapy was given prior to the transplant which was uncomplicated. In the second
      case strongyloidiasis was diagnosed post transplant which was complicated by
      infection and respiratory compromise. Fatal hyperinfection subsequently developed
      after corticosteroid therapy was started for a disease progression in the CNS.

PMID- 12815489
TI  - Utility of antigenemia test for cytomegalovirus detection in hematopoietic
      transplant recipients: report of experiences from Medellin, Colombia.

PMID- 12815490
TI  - Measurement and analysis of visual acuity in multicenter randomized clinical
      trials in the United States: findings from a survey.
AB  - PURPOSE: To describe visual acuity (VA) testing and scoring methods used in
      multicenter randomized clinical trials in ophthalmology in the United States
      (USA) sponsored by the National Eye Institute (NEI). METHODS: A survey was
      conducted among multicenter studies in the US that included one or more
      randomized clinical trials and were sponsored by the NEI, National Institutes of
      Health. To be included in the survey, a study had to have VA reported in one or
      more publications or patient eligibility based on VA, a majority of study
      subjects 13 years of age or older, and a patient population primarily or
      exclusively from the US. A standard survey form was completed for each study
      based on information presented in the study manual of procedures and
      publications. Findings were summarized and displayed with frequency
      distributions. RESULTS: The survey included 24 studies, each with enrollment
      initiated in the period 1972 to 1999. VA was one of the study eligibility
      criteria for 19 (79%) studies, and VA or change in VA was the primary outcome in
      12 (50%) studies. ETDRS charts have been employed in 16 of 19 studies initiated
      after the charts were published in 1982. All studies but one specified in the
      documents reviewed that VA testing was performed at multiple VA test distances.
      For studies that used ETDRS charts, methods of converting VA scores obtained at
      different test distances to a common scale fell into two categories: 11 studies
      used a method similar in nature to that first reported in the Macular
      Photocoagulation Study, and 7 studies used a method similar in nature to that
      first reported in the Krypton-Argon Regression of Neovascularization Study.
      conclusion The development of the ETDRS charts and a custom light box has led to
      more uniformity in VA test charts and chart illumination. However, details of VA
      measurement protocols vary widely from study to study. To assure comparable data
      across studies and ocular conditions, it would be useful to have a standard VA
      testing and scoring protocol with provisions for testing different levels of
      visual acuity that recommends a single method for converting scores from
      different test distances to a common scale and standard conversion of "off the
      chart" VA levels for calculation of means and changes in VA.

PMID- 12815491
TI  - Azithromycin treatment coverage in Tanzanian children using community volunteers.
AB  - PURPOSE: To determine which of two village-based strategies was more effective at
      recruiting residents for a trachoma mass treatment campaign. METHODS: The two
      strategies were to use either village government personnel to recruit residents
      for treatment, or to solicit interested community volunteers to recruit
      residents. Three were villages assigned to each strategy, and the outcome
      measured was treatment coverage of individuals, group and the villages. RESULTS:
      Self-selected community volunteers were significantly more effective than village
      government personnel in recruiting villagers for antibiotic treatment (p <.0001).
      The differences were strongest for the group at highest risk for active trachoma,
      pre-school children; 73% of children in community volunteer villages were
      treated, compared to 63% in village government villages (p <.05). Children in
      villages using community volunteers and from larger families were more likely to
      be treated. CONCLUSION: These findings support using motivated community
      volunteers, rather than traditional government workers, for mass treatment
      campaigns where high coverage is necessary.

PMID- 12815492
TI  - Health-related quality of life of cataract patients: cross-cultural comparisons
      of utility and psychometric measures.
AB  - BACKGROUND: This study was conducted to assess the presence and/or absence of
      cross-cultural differences or similarities between Korean and United States
      cataract patients. A systematic assessment was performed using utility and
      psychometric measures in the study population. RESEARCH DESIGN: A cross-sectional
      study design was used to examine the comparison of preoperative outcomes measures
      in cataract patients in Korea and the United States. Study subjects were selected
      using non-probabilistic methods and included 132 patients scheduled for cataract
      surgery in one eye. PARTICIPANTS: Subjects were adult cataract patients at
      Samsung and Kunyang General Hospital in Seoul, Korea, and Tulane University
      Hospital and Clinics in New Orleans, Louisiana. MEASUREMENTS: Preoperative
      utility was assessed using the verbal rating scale and standard reference gamble
      techniques. Current preoperative health status was assessed using the SF-36 and
      VF-14 surveys. Current preoperative Snellen visual acuity was used as a clinical
      measure of vision status. RESULTS: Korean patients were more likely to be younger
      (p = 0.001), less educated (p = 0.001), and to have worse Snellen visual acuity
      (p = 0.002) than United States patients. Multivariate analysis of variance
      (MANOVA) revealed that in contrast to Korean patients, United States patients
      were assessed to have higher scoring in general health, vitality, VF-14, and
      verbal rating for visual health. This higher scoring trend persisted after
      controlling for age, gender, education and Snellen visual acuity. The difference
      in health-related quality of life (HRQOL) between the two countries was quite
      clear, especially in the older age and highly educated group. CONCLUSIONS:
      Subjects in Korea and the United States were significantly different in quality
      of life, functional status and clinical outcomes. Subjects in the United States
      had more favorable health outcomes than those in Korea. These differences may be
      caused by multiple factors, including country-specific differences in economic
      status, health care system, cultural value system, and health policy. Cross
      cultural differences should be considered when making international comparisons
      of quality of life.

PMID- 12815493
TI  - A randomized trial of visual impairment interventions for nursing home residents:
      study design, baseline characteristics and visual loss.
AB  - INTRODUCTION: Visual impairment among nursing home residents is higher than in
      community-dwelling elderly. The provision of eye care services may be beneficial
      to nursing home patients. Our project, a randomized trial of vision restoration
      and rehabilitation in nursing home residents, compares usual care to targeted
      interventions. In this paper, we present the baseline characteristics of our
      sample within the nursing homes. METHODS: Twenty-eight nursing homes on
      Maryland's Eastern Shore were matched in pairs by size and payment type. Each
      pair was randomized to usual care or targeted intervention. Habitual and best
      corrected acuity was attempted, using standard letter symbol/charts and grating
      acuity charts. Visual impairment was vision in the better eye <20/40 on letter
      and/or grating acuity. The MiniMental State Examination (MMSE) was used to
      determine cognitive impairment. RESULTS: Of those participants eligible to be
      screened, 40% had severe cognitive impairment (MMSE score 0-9). No measure of
      acuity could be ascertained on 18% of eligibles. Among the 1305 persons with
      acuity data, 38% had presenting vision worse than 20/40. After refractive
      correction, 29% had visual impairment. There was no difference by race or gender
      in those with visual impairment, although they were older, compared to those
      without visual loss. CONCLUSIONS: The nursing home residents had high rates of
      both cognitive impairment and visual impairment, creating a challenging
      environment for visual intervention. By improving access to eye care within the
      context of the clinical trial, and changing either the magnitude of visual loss
      or the resultant impact on function, we hope to demonstrate a change in the
      quality of life for nursing home residents.

PMID- 12815497
TI  - The concept of cognitive reserve: a catalyst for research.

PMID- 12815498
TI  - Genetic evidence for cognitive reserve: variations in memory and related
      cognitive functions.
AB  - Variations in cognitive functions across individuals are observed universally,
      and such observations serve as the basis of cognitive reserve (CR). Broadly,
      cognitive reserve refers to the inconsistency between neuropathology and clinical
      severity. The causes of such individual variations are likely to be multi
      factorial. In this review, I present studies which suggest that genes are likely
      to be the contributing causes, and these genes interact with environmental
      factors to produce even greater variations in cognitive functions. A number of
      animal and human studies are beginning to reveal the role of genetic
      contributions to cognitive functions like memory, memory decline, general
      intelligence, and language. Twin studies suggest that there is a substantial
      heritable component for memory and related cognitive functions, such as general
      intelligence and language, but not for others. Thus, heritability estimates vary
      by cognitive domain. Animal studies and some human studies have identified genes
      or candidate loci that contribute to memory as well as other related cognitive
      phenotypes. Yet, our current understanding is limited. It will require
      interdisciplinary efforts from a number of different fields to better define the
      neuropsychological phenotype. At the same time, it is necessary to take into
      account both genetic and environmental factors to understand the complex network
      underlying CR.

PMID- 12815499
TI  - Lifetime antecedents of cognitive reserve.
AB  - We used path analysis on data from the British 1946 birth cohort to model
      lifetime antecedents of cognitive reserve, represented by the NART at 53 years,
      and compared this model for verbal memory and psychomotor function at this age,
      cognitive outcomes that are sensitive to age-associated decline. We showed
      independent paths from childhood cognition, educational attainment and adult
      occupation to cognitive reserve, with that from childhood cognition the
      strongest, and that from adult occupation the weakest. A similar pattern was
      found for the verbal memory and psychomotor outcomes, although the pathways were
      weaker than those to the NART. The pattern was also mirrored by the paths from
      paternal occupation to childhood cognition, educational attainment and adult
      occupation, with that to childhood cognition the strongest, and that to adult
      occupation the weakest. The direct influence of paternal occupation on cognitive
      reserve was negligible, and almost entirely mediated by childhood cognitive
      ability and educational attainment.

PMID- 12815500
TI  - Cognitive reserve and lifestyle.
AB  - The concept of cognitive reserve (CR) suggests that innate intelligence or
      aspects of life experience like educational or occupational attainments may
      supply reserve, in the form of a set of skills or repertoires that allows some
      people to cope with progressing Alzheimer's disease (AD) pathology better than
      others. There is epidemiological evidence that lifestyle characterized by
      engagement in leisure activities of intellectual and social nature is associated
      with slower cognitive decline in healthy elderly and may reduce the risk of
      incident dementia. There is also evidence from functional imaging studies that
      subjects engaging in such leisure activities can clinically tolerate more AD
      pathology. It is possible that aspects of life experience like engagement in
      leisure activities may result in functionally more efficient cognitive networks
      and therefore provide a CR that delays the onset of clinical manifestations of
      dementia.

PMID- 12815501
TI  - Assessment of lifetime participation in cognitively stimulating activities.
AB  - Cognitively stimulating experience is thought to contribute to cognitive reserve.
      We constructed a questionnaire consisting of 25 items about frequency of
      participation in cognitive activities across the life span and administered it to
      two groups of older persons. The total score on the scale had high internal
      consistency (coefficient alpha = 0.88) and temporal stability over a 4-week re
      test interval (r = 0.79), and it was positively correlated with education. In
      analyses controlling for age, sex, and education, more frequent cognitive
      activity was related to better perceptual speed, visuospatial ability, and
      semantic memory but not to episodic memory or working memory. The results suggest
      that the scale provides a psychometrically sound measure of frequency of
      cognitive activity across the life span.

PMID- 12815502
TI  - Early life physical activity and cognition at old age.
AB  - Physical activity has shown to be inversely associated with cognitive decline in
      older people. Whether this association is already present in early life has not
      been investigated previously. The association between early life physical
      activity and cognition was studied in 1,241 subjects aged 62-85 years, in a
      prospective population-based study. Physical activity between ages 15 and 25
      years was asked retrospectively. The findings suggest a positive association
      between regular physical activity early in life and level of information
      processing speed at older age in men, not in women. The association could not be
      explained by current physical activity or other lifestyle factors. This finding
      supports the cognitive reserve hypothesis, and might suggest that early life
      physical activity may delay late-life cognitive deficits.

PMID- 12815503
TI  - Psychosocial risk factors of HIV morbidity and mortality: findings from the
      Multicenter AIDS Cohort Study (MACS).
AB  - Despite the use of laboratory markers in estimating HIV prognosis, significant
      variation in the natural history of HIV-1 infection remains unexplained. Recent
      studies suggest psychosocial risk factors have important prognostic significance
      in HIV disease. The objective of the present study was to examine the prognostic
      influence of age, general intellectual functioning, and emotional distress across
      the spectrum of HIV disease progression. The study sample was drawn from the
      Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV
      seropositive men recruited from four study centers across the country. The
      participants were 1,231 HIV-seropositive MACS participants, followed from
      baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV
      disease progression was evaluated with respect to three outcome measures: (1)
      number of years from baseline testing to the first AIDS defining illness
      (progression to AIDS), (2) years from baseline to HIV-dementia (progression to
      dementia), and (3) years from baseline to death (survival). The influence of
      psychosocial risk factors on outcome measures was evaluated using survival
      analyses. General intellectual functioning, age, and somatic symptoms of
      depression, were found to be significant predictors of HIV disease progression
      and survival. Older age at baseline was associated with a more rapid progression
      to dementia and death. Lower Shipley IQ estimates were associated with a more
      rapid disease progression (AIDS and dementia) and shortened survival. Somatic
      symptoms of depression were associated with shortened survival. In addition, age,
      IQ, and somatic symptoms of depression, had an additive effect with an increase
      in the number of risk factors associated with accelerated disease progression and
      shortened time to death. These findings remained consistent, despite controlling
      for baseline CD4 and HIV medication use. Psychosocial cofactors are important in
      understanding HIV disease progression. Methods for estimating HIV prognosis may
      become more reliable if psychosocial factors are considered. Future research will
      clarify if psychosocial risk factors reflect central nervous system integrity,
      brain reserve capacity or mediate morbidity and mortality through social economic
      status, access to health care and other social correlates.

PMID- 12815504
TI  - Head circumference, education and risk of dementia: findings from the Nun Study.
AB  - To examine the prevalence of dementia associated with having a smaller brain,
      lower education or both of these characteristics, 294 Catholic sisters were
      assessed annually for dementia. Sixty participants died and their brains were
      evaluated to determine fulfillment of neuropathological criteria for Alzheimer's
      disease (AD). Lower educational attainment and the interaction of smaller head
      circumference with lower education were associated with the presence of dementia,
      controlling for age and the presence of one or more apolipoprotein E-epsilon 4
      alleles. By contrast, neither low educational attainment nor head circumference
      was significantly associated with fulfillment of neuropathological criteria for
      AD. Individuals having both low education and small head circumference were four
      times as likely to be demented as the rest of the sample. The findings suggest
      that higher education and larger head size, alone or in combination, may reduce
      the risk of expressing dementia in late life.

PMID- 12815505
TI  - Literacy and memory decline among ethnically diverse elders.
AB  - Literacy may be a more powerful indicator of brain reserve than years of
      education. Literacy level may be a proxy for native intellectual capacity or life
      experience that can compensate for brain damage or provide brain reserve.
      Alternately, the experience of acquiring literacy skills may in itself change the
      organization of the brain and increase protection against cognitive decline.
      However, because people with low levels of literacy obtain poor scores on most
      cognitive measures, only longitudinal studies can elucidate the role of reading
      ability in reserve. We determined whether literacy skills could predict cognitive
      change in a sample of 136 English-speaking African American, Caucasian, and
      Hispanic elders selected from a longitudinal aging study in New York City.
      According to a physician's independent examination, all participants were
      nondemented throughout the four longitudinal assessments. Literacy level was
      assessed using the WRAT-3 reading subtest. After accounting for age at baseline
      and years of education, GEE analyses showed that elders with low levels of
      literacy had a steeper decline in both immediate and delayed recall of a word
      list over time as compared to high literacy elders. Our findings suggest that
      literacy skills are protective against memory decline among nondemented elders.

PMID- 12815506
TI  - Exploring the neural basis of cognitive reserve.
AB  - There is epidemiologic and imaging evidence for the presence of cognitive
      reserve, but the neurophysiologic substrate of CR has not been established. In
      order to test the hypothesis that CR is related to aspects of neural processing,
      we used fMRI to image 19 healthy young adults while they performed a nonverbal
      recognition test. There were two task conditions. A low demand condition required
      encoding and recognition of single items and a titrated demand condition required
      the subject to encode and then recognize a larger list of items, with the study
      list size for each subject adjusted prior to scanning such that recognition
      accuracy was 75%. We hypothesized that individual differences in cognitive
      reserve are related to changes in neural activity as subjects moved from the low
      to the titrated demand task. To test this, we examined the correlation between
      subjects' fMRI activation and NART scores. This analysis was implemented voxel
      wise in a whole brain fMRI dataset. During both the study and test phases of the
      recognition memory task we noted areas where, across subjects, there were
      significant positive and negative correlations between change in activation from
      low to titrated demand and the NART score. These correlations support our
      hypothesis that neural processing differs across individuals as a function of CR.
      This differential processing may help explain individual differences in capacity,
      and may underlie reserve against age-related or other pathologic changes.

PMID- 12815507
TI  - Cognition and aging: a highly selective overview of event-related potential (ERP)
      data.
AB  - An overview of highly selected cognitive aging investigations of deviance
      detection, episodic memory and working memory reveals two primary themes: (1)
      when variability in elderly samples has been assessed, it has proven useful in
      understanding age-related changes in cognition; and (2) there is a frontal lobe
      contribution to at least some age-related changes in cognition. However, there
      are too few ERP age-related investigations of individual differences to determine
      whether the changes in patterns of ERP responding can be deemed "compensatory" or
      "inefficient." It is suggested that, to the extent possible, future
      electrophysiological investigations of cognitive aging (as well as other
      physiological measurement techniques) include individual difference measures that
      will enable the determination of the implication of a given neural pattern in the
      genesis of a given, age-related behavioral outcome pattern.

PMID- 12815508
TI  - Adult neurogenesis: a mechanism for brain repair?
AB  - It is now generally accepted that new neurons are added to the adult mammalian
      brain. This raises the possibility that naturally occurring neurogenesis may be
      useful for repairing the damaged adult brain. Indeed, several studies have shown
      that damage to the adult brain can stimulate reparative neurogenesis. However,
      the production of new neurons is only one of several steps necessary to restore
      damaged neural circuits to their original state. Studies carried out on intact
      animals have identified several conditions that affect the production and
      survival of new neurons in adult brains. This review considers the evidence for
      compensatory neurogenesis in the adult mammalian brain with a view toward
      applying information from the undamaged brain to studies of regeneration.

PMID- 12815511
TI  - Using the TOMM for evaluating children's effort to perform optimally on
      neuropsychological measures.
AB  - Suboptimal effort is a threat to the validity of neuropsychological evaluations.
      Numerous papers have been devoted to this subject and a large number of measures
      have been developed in an attempt to detect suboptimal effort. To date, however,
      the clinical literature has focused almost exclusively on identifying suboptimal
      effort in adults, whereas suboptimal effort among children has not been addressed
      thoroughly in the clinical neuropsychological literature. The present study
      investigated whether or not already established effort measures could be used
      with children. The Test of Memory Malingering (TOMM) and the Rey-15-item test
      were administered to 128 children in two sites, the USA and Cyprus. The results
      indicated that the TOMM has the potential to be used as a measure for identifying
      children who do not put forth maximal effort during neuropsychological
      evaluations. In contrast, the Rey-15-item test does not appear to be a promising
      measure of effort for use with children, especially younger children.

PMID- 12815512
TI  - Time reproduction in children with ADHD: motivation matters.
AB  - The primary goal of this study was to examine whether children with ADHD have a
      true deficit in subjective time sense, or whether their impairment reflects a
      motivational deficit. Thirty children with ADHD and 30 matched control children
      completed two versions of a time reproduction paradigm ("Regular" and "Enhanced")
      in which motivational level was manipulated by the addition of positive sham
      feedback and the prospect of earning a reward. A secondary goal was to
      investigate performance on measures of working memory and behavioural inhibition,
      and how those constructs relate to time reproduction in the context of Barkley's
      (1997a) model of ADHD. Children with ADHD performed significantly better on the
      motivating 'Enhanced' versus the Regular time reproduction paradigm, although
      they continued to perform significantly worse than controls on both tasks.
      Control children exhibited no reliable change in performance between versions of
      the task. Significant group differences were also observed on the working memory
      and behavioural inhibition tasks. We discuss the impact of motivation, working
      memory, and behavioural inhibition on time reproduction performance.

PMID- 12815513
TI  - Age related effects in children taking the computerized assessment of response
      bias and word memory test.
AB  - The assessment of effort is a fundamental component of test performance analysis,
      since effort determines whether a psychological evaluation is valid. The
      assessment of effort in children has proven problematic. This may be related to
      the variable and inconsistent nature of children's developing self-regulatory
      systems, and the fact that measures commonly used to assess effort were
      standardized on adults. If one uses effort measures designed for adults to assess
      children, then one must presume that the maintenance of effort in children is
      comparable to the same behavior in adults. However, because children's executive
      functioning, including their abilities to self-regulate, attend, concentrate, and
      to engage in various cognitive activities improve with time (Barkley, 1997, pp.
      209-234), our hypothesis is that young children's effort regulation is dissimilar
      to that of adults, and the presumption of similarity is implausible. The purpose
      of this study was to determine whether age is a significant influence upon young
      children's performances on the Computerized Assessment of Response Bias (CARB)
      and Word Memory Test (WMT). Statistical analysis suggests that younger children
      (those under 10 years of age) tended to produce poorer performance on these
      instruments. Younger children's scores differed significantly from children ages
      10 and older. Children 11 years and older produced CARB and WMT results similar
      to adult participants, suggesting a viability for adult normative comparisons
      with children in this age range. The current investigation concluded that
      children's maintenance of effort appears to be significantly related to age and
      reading ability level. Consequently, the use of current adult-based norms with
      the CARB and WMT, without regard for a child's developmental status and other
      contextual factors such as the child's ability to read, appears ill-advised
      especially with children under 11 years of age.

PMID- 12815514
TI  - Neurocognitive impairment in early adolescence following prenatal alcohol
      exposure of varying duration.
AB  - The aims of the study were, first, to perform a comprehensive assessment of
      neurocognitive status in early adolescence of children exposed to alcohol
      prenatally; and, second, to examine whether duration of exposure continues to be
      predictive of outcome at this age. Twenty-seven exposed 12-14-year-olds and 39
      non-exposed 13-14-year-olds underwent neuropsychological assessments (WISC-III,
      NEPSY subtests) of attention and executive functions, language, visuomotor
      functions, and memory. The group of non-exposed children was used to develop
      preliminary test norms for the 13-14-year-old exposed children whereas published
      test norms could be used for the 12-year-olds. The results demonstrated
      neurocognitive impairment across all types of tasks. Impairment varied in degree
      according to the duration of alcohol exposure. Children exposed throughout
      pregnancy, most of who had diagnoses of Fetal Alcohol Syndrome (FAS) or Fetal
      Alcohol Effects (FAE), performed well below the average range. It was concluded
      that the neurocognitive effects of alcohol exposure tend to be widespread and
      generalized. Attention and executive functions do not seem to be selectively
      affected. Further, the relationship between duration of prenatal alcohol exposure
      and neurocognitive development continues to be significant in early adolescence.

PMID- 12815515
TI  - Interstitial deletion on chromosome 5q33.3q35.1 in a 6-year-old girl --
      neuropsychological findings and follow-up in an extremely rare chromosomal
      aberration.
AB  - Interstitial deletion on chromosome 5q33.3q35.1 is an extremely rare chromosomal
      aberration for which a characteristic syndrome could not yet be delineated. In
      most patients with 5q deletions severe mental retardation is described. Recently,
      Spranger et al. (2000) described the case of a 4-year-old girl with a de novo
      deletion on 5q33.3q35.1 presenting only with mild psychomotor delay, minor facial
      anomalies, and seizures. The patient was admitted for outpatient
      neuropsychological assessment when she was 6.2 years old. Neurocognitive tests
      revealed an overall developmental delay of about 32 months and an intelligence
      score in the range of mild mental retardation. Her cognitive phenotype was
      characterized by a considerable visual-spatial deficit in the form of
      disorganized drawings or block designs indicating a profound lack of cohesion and
      overall global organization (decay of gestalt). The patient's behavioral
      phenotype was dominated by a distinct disinhibition syndrome demonstrating severe
      hyperactivity, utilization behavior, and aggressive behavior.

PMID- 12815516
TI  - Risk for injury in preschoolers: relationship to attention deficit hyperactivity
      disorder.
AB  - Parental ratings of preschoolers' risk for injury, direct assessment of
      preschoolers' behavior thought related to risk for injury (e.g., Inattention,
      impulsivity) and number of documented injuries were examined in preschoolers with
      Attention Deficit Hyperactivity Disorder (ADHD) and their non-ADHD peers
      (Control). Of preschoolers with ADHD, 58.3% exhibited behavior which placed them
      at-risk for physical injury (0% Control), and their performance was significantly
      poorer on clinic-based tests. Nonetheless, preschoolers with ADHD did not
      actually sustain significantly more injuries which warranted medical treatment in
      an emergency department. Although preschoolers with ADHD may be at increased risk
      for minor injuries, further research is needed to determine whether they more
      frequently sustain more serious injuries.

PMID- 12815518
TI  - Causal inference in lead research: introduction to the special section on the
      neurobehavioral effects of environmental lead.
AB  - This Special Section on the Neurobehavioral Effects of Environmental Lead
      includes empirical reports from three major longitudinal prospective studies and
      a review of animal research modeling effects of lead on human cognition. This
      Introductory article addresses a fundamental controversy in lead and other
      epidemiologic research. It is argued that, contrary to conventional wisdom, valid
      causal inferences can be made from correlational research. Justification for this
      is to be found in contemporary frameworks drawn from the field of the philosophy
      of science; an essential, but often neglected perspective for such
      metatheoretical issues as causal inference. It is concluded that the
      nonexperimental methods described in the articles comprising this Special Section
      can, indeed, contribute to causal formulations of lead effects on human
      development, and that such inferences are not exclusive to experimental evidence.

PMID- 12815519
TI  - Cognitive development of lead exposed children from ages 6 to 15 years: an
      application of growth curve analysis.
AB  - The effect of lead exposure on cognitive growth patterns was assessed in a
      longitudinal study of 196 children. Performances on tests of verbal comprehension
      and perceptual organization (Vocabulary & Block Design, Wechsler Intelligence
      Scales for Children) were measured at ages 6.5, 11 and 15 years. Growth curve
      analyses revealed that the quadratic model best described the relationship
      between test scores and age. Children with higher lead levels, as measured at age
      15 years, demonstrated lower verbal comprehension scores over time and greater
      decline in their rate of Vocabulary development at age 15 years, as compared to
      children with lower lead levels. Lead exposure was not significantly associated
      with growth in perceptual organization test scores. Socioeconomic status and
      maternal intelligence were statistically significantly associated with growth
      patterns for both test scores, independent of the effects of lead. The findings
      suggest that lead negatively impacts the developmental progression of specific
      cognitive skills from childhood through adolescence.

PMID- 12815520
TI  - The relationship between blood lead, bone lead and child intelligence.
AB  - We report associations between serial measures of blood lead and intelligence in
      children age 10-12 years, half heavily exposed to lead from the prenatal period
      onward, and half relatively unexposed. For a subsample, we examine bone lead-IQ
      associations, comparing them with bone lead associations. Both blood and bone
      lead levels were associated with intelligence decrements, small relative to the
      contribution of social factors. For each doubling of Tib-Pb, Full Scale,
      Performance, and Verbal IQ decreased by an estimated 5.5, 6.2, and 4.1 points,
      respectively. Bone lead-IQ associations were stronger than those for blood lead,
      which nonetheless provide robust analogues. Current BPb, easy to obtain, provides
      a useful means for assessing Pb exposure/IQ associations.

PMID- 12815521
TI  - Low-level lead exposure, executive functioning, and learning in early childhood.
AB  - The current paper presents evidence relating low-level lead exposure to impaired
      executive functioning in young children. Using the Shape School task, we assessed
      focused attention, attention switching, working memory, and the ability to
      inhibit automatic responses in a cohort of 170 children. Participants performed
      the Shape School task at both 48 and 54 months of age; the mean blood lead level
      was 6.49 microg/dl at 48 months. After controlling for a wide range of
      sociodemographic, prenatal, and perinatal variables, blood lead level was
      negatively associated with children's focused attention while performing the
      tasks, efficiency at naming colors, and inhibition of automatic responding. In
      addition, children with higher blood lead levels completed fewer phases of the
      task and knew fewer color and shape names. There was no association between blood
      lead and performance on the most difficult tasks, those requiring attention
      switching or the combination of inhibition and switching. Children's IQ scores
      were strongly associated with blood lead and Shape School performance, and when
      entered as a covariate, only color knowledge and the number of tasks completed
      remained significant. Results provide only weak support for impaired executive
      functioning, but the deficits in color knowledge may indicate a primary sensory
      deficit or difficulty with forming conditional associations, both implicating
      disruptions in dopamine system function.

PMID- 12815522
TI  - Lead-induced impairments in complex cognitive function: offerings from
      experimental studies.
AB  - Experimental studies, relying primarily on rodent and non-human primate models,
      have produced compelling evidence supporting effects of chronic low level lead
      exposure on learning, with the magnitude of those effects possibly modulated by
      developmental period of exposure and learning paradigm parameters. In contrast,
      changes in memory are not systematically demonstrated. The impact of lead
      exposure on attention has yet to be clearly delineated in either human or
      experimental studies, although impulsivity or aversion to delay appears to be a
      sensitive component of attention that may be targeted.

PMID- 12815524
TI  - The expandability of the eye in childhood myopia.
AB  - PURPOSE: While intraocular pressure has been shown to have some influence on eye
      growth, the stress exerted on the outer wall of the eye and the rigidity of the
      outer coats of the eye may be of greater importance. No studies have assessed the
      significance of both of these variables in terms of childhood myopia and its
      progression. METHODS: Twenty myopic and twenty non-myopic children aged 8 to 12
      years participated in the study. Refractive error (including refractive error
      shift over the past year), ocular dimensions (anterior chamber, lens thickness,
      vitreous chamber, axial length), intraocular pressure, equatorial scleral
      rigidity, and outer wall thickness were measured for right eyes. Outer wall
      stress was calculated using the approximation, p = IOP*r/2t. RESULTS: The myopic
      group was 3.43 D more myopic and had 1.43 mm longer eyes on average than the non
      myopic group. The myopic children had experienced a mean refractive shift of 
      0.30 D/yr over the past year. Equatorial wall thickness was significantly less in
      myopes than non-myopes (difference of 0.09 mm, p = 0.02) and in the combined
      sample was correlated to refractive error (r = 0.312, p = 0.05), but not
      refractive error shift. Ocular rigidity and eye wall stress values were similar
      in the two groups. The refractive shift increased as wall stress increased both
      in the combined sample (r = -0.386, n = 35, p = 0.022) and the myopic group (r = 
      0.600, n = 16, p = 0.014). CONCLUSION: We did not find large differences in wall
      thickness, ocular rigidity, or wall stress in myopic and non-myopic children.
      While reduced ocular rigidity, increased wall stress and scleral thinning may
      have a role in myopia progression in childhood we were not able to clearly show
      this in our study of 40 children.

PMID- 12815525
TI  - Effect of local macrophage depletion on cellular immunity and tolerance evoked by
      corneal allografts.
AB  - Corneal graft rejection can be prevented by local macrophage depletion, via
      subconjunctival injections with clodronate liposomes. To unravel the underlying
      immunological mechanism responsible for prolonged graft survival in this
      circumstance, the effect of this regimen on induction of donor-specific delayed
      type hypersensitivity (DTH) and anterior chamber associated immune deviation
      (ACAID) was determined. The study showed that although subconjunctival clodronate
      liposome-treatment failed to alter systemically induced DTH and ACAID, both types
      of immune response were absent in clodronate liposome-treated rats after corneal
      transplantation. Thus, elimination of macrophages from the corneal transplant
      site renders corneal allografts immunologically "invisible" to the recipient.
      PURPOSE: To determine whether local macrophage depletion, via administration of
      clodronate liposomes, alters delayed type hypersensitivity (DTH) responses and
      induction of anterior chamber associated immune deviation (ACAID) after corneal
      allotransplantation. METHODS: Clodronate liposome-treated and untreated rats
      received orthotopic corneal allografts and were tested for DTH responses and
      induction of ACAID towards donor antigens. Also in subconjunctivally treated and
      untreated rats, DTH responses were measured after subcutaneous immunization or
      induction of ACAID with allogeneic spleen cells. RESULTS: Subconjunctival
      injected clodronate liposomes prevented grafted rats from developing donor
      specific DTH as well as ACAID. By contrast, subconjunctivally injected clodronate
      liposomes had no effect on donor-specific DTH responses after systemic
      immunization or on the induction of ACAID with allogeneic cells. CONCLUSIONS:
      Depletion of macrophages at the time of corneal allografting seems to render the
      grafts immunologically invisible to the recipients. This could explain why these
      grafts survive "indefinitely" without any other form of therapy.

PMID- 12815526
TI  - Autologous transplantation of retinal pigment epithelium after mechanical
      debridement of Bruch's membrane.
AB  - PURPOSE: To determine whether transplantation of autologous retinal pigment
      epithelium (RPE) will prevent atrophy of the choriocapillaris and loss of
      photoreceptors in an area in which the RPE has been mechanically debrided from
      Bruch's membrane. METHODS: Abrasive debridement of RPE was performed with a metal
      cannula after localized retinal bleb detachments in two separate areas of the
      rabbit retina. The RPE cell suspension aspirated from one of the debridement
      sites was transplanted to the other. The debridement-only site served as control.
      The transplant and control sites were evaluated after 30 days by color fundus
      photography, fluorescein angiography, light microscopy and transmission electron
      microscopy. RESULTS: Compared with debridement only, debridement plus
      transplantation of RPE resulted in more complete repopulation of the bare Bruch's
      membrane surface with relative preservation of choriocapillaris and
      photoreceptors. CONCLUSION: Autologous transplantation of RPE onto an abrasively
      debrided Bruch's membrane decreases choriocapillaris atrophy and photoreceptor
      loss.

PMID- 12815527
TI  - Polar lipids in human meibomian gland secretions.
AB  - PURPOSE: To determine the polar lipid composition of human meibomian gland
      secretions and their relationship to the preocular tear film. METHODS: Meibomian
      secretions were collected from normals and patients with chronic blepharitis.
      These lipids (meibum) were first separated by thin layer chromatography. Polar
      lipids were then separated utilizing high-pressure liquid chromatography with
      ultraviolet detection. Individual peaks were identified by comparison with
      standards. Collected sample peaks were subjected to differential transmethylation
      with sodium methoxide-methanol and the resulting fatty acid methyl esters were
      analyzed by gas chromatography-mass spectroscopy. RESULTS: Three phospholipids
      were identified as phosphatidylcholine, phosphatidylethanolamine and
      sphingomyelin; other unidentified phospholipids were also present. Also present
      in secretions were the sphingolipids ceramides and cerebrosides. Fatty acids
      present were 12-18 carbon chain length. All fatty acids were normal (not
      branched) saturated fatty acids except in sphingolipids, where hydroxy fatty
      acids were also present. Unsaturated normal fatty acids were present only in
      meibum from patients with meibomianitis. CONCLUSIONS: The composition of the
      polar lipids in meibomian gland secretions is more complex than previously
      thought. On the other hand, the type and carbon chain length of the polar lipid
      fatty acids appears strictly controlled. The relationship of these findings to
      the preocular tear film should be considered in terms of overall functionality.
      The polar lipid layer most likely is only one to three molecules thick and serves
      as a surfactant between aqueous tears and the thicker nonpolar lipid layer.

PMID- 12815528
TI  - Beta-adrenergic inhibition of rabbit lens anterior-surface K(+) conductance.
AB  - PURPOSE: To characterize the effects of cAMP-elevating stimuli on the rabbit
      translens electrical parameters and examine the distribution of beta
      adrenoceptors about the epithelial surface. METHODS: The electrophysiological
      experiments encompassed the isolation of lenses within a vertically arranged,
      Ussing-type chamber under short-circuit conditions, an approach that allowed for
      measurements of short-circuit current (I(sc)) across, in separate experiments,
      discrete surface regions. Epithelial beta receptors were localized by
      immunofluorescent labeling of lens cryosections primarily exposed to a polyclonal
      antibody against human beta( 2)-adrenoceptors. Reverse transcription - polymerase
      chain reaction (RT-PCR) was used to generate cDNA (using specific primers based
      upon the sequence of the previously cloned human beta(2) receptor) from rabbit
      lens RNA extracted from mechanically sequestered anterior and equatorial
      epithelial cells. RESULTS: Asymmetrical I(sc) reductions with increases in
      translens resistance were elicited with epinephrine, isoproterenol, terbutaline,
      forskolin, and a lipid-permeable cAMP analogue. Electrical changes were recorded
      across the anterior aspect and not observed when the above compounds were applied
      to solutions bathing the equatorial and posterior surfaces. Immunohistochemical
      observations indicated the expression of beta receptors from the anterior
      epithelium to the equatorial region. RT-PCR yielded cDNA of expected basepair
      length for the apparent fragment of the beta(2)-adrenoceptor, which exhibited a
      sequence homology 90% identical with its human equivalent in both the anterior
      and equatorial epithelia. CONCLUSIONS: The cAMP-sensitive conductance(s) appear
      limited to the anterior epithelium and undetectable equatorially. The
      asymmetrical I(sc) responses do not seem to arise from a spatial heterogeneity in
      epithelial receptor expression.

PMID- 12815529
TI  - Intravitreal injection of dispase causes retinal hemorrhages in rabbit and human
      eyes.
AB  - PURPOSE: To check the effects of intravitreally injected dispase in the vitreo
      retinal region. METHODS: Dispase, 0.05 to 2.5 units dissolved in 100 microl of
      phosphate-buffered saline, was injected into the midvitreous of rabbits which
      were killed from 15 to 120 min afterwards. The enzyme was also injected into four
      human eyes of patients with orbital tumors 15 min before enucleation during
      orbital exenteration surgery. The eyes were examined in vivo as well as by light
      and electron microscopy. RESULTS: Hemorrhages were detected by fundus
      observations and confirmed by microscopical analysis in nearly all rabbits and in
      half of the human eyes. The red blood cells were observed in the vitreous and
      retina. Breaches in the inner limiting membrane were visualized in human eyes and
      ruptures of small blood vessels in rabbit eyes. In spite of that, vitreous
      detachment was not verified. In fact, the cortical-vitreous collagen-fibril
      network was conspicuous on scanning electron micrographs. CONCLUSIONS: Retinal
      hemorrhages were evident as early as 11 min after injection. It is suggested that
      this enzyme degraded selectively basement membrane components without affecting
      other proteins involved in the vitreous-retinal junction.

PMID- 12815530
TI  - Comparison of efficacy of topical and oral fluconazole treatment in experimental
      Aspergillus keratitis.
AB  - PURPOSE: To investigate the therapeutic role of topical and oral fluconazole
      treatment using a rabbit model of Aspergillus fumigatus keratitis. METHODS:
      Aspergillus fumigatus spores were injected into the corneal stroma of the right
      eye of 20 rabbits. Forty-eight hours later the rabbits were randomly divided into
      three groups. Group 1 rabbits (six) were treated with topical fluconazole (2
      mg/ml, eight times daily), group 2 rabbits (seven) received oral fluconazole
      (37.5 mg/kg bid), and group 3 rabbits (seven) were untreated controls. The eyes
      were examined and photographed with a slit-lamp 2, 6, 10, 16, and 20 days after
      inoculation and an observer graded the corneas in a masked fashion. Corneal
      cultures were taken on days 2, 14, and 20 for fungus growth. RESULTS: At the
      beginning of treatment, the slit-lamp scores did not differ among three groups.
      However, on days 6, 10, 16, and 20 the treated groups had statistically
      significant lower scores compared to the untreated controls. No significant
      difference was observed between topical and oral treated groups at any
      examination point. All cultures were positive on day 2, but on days 16 and 20,
      there were significantly lower positive fungal cultures in both treatment groups
      compared to the control (p < 0.01, chi square test). CONCLUSION: Our study showed
      that both topical and oral fluconazole were effective in lessening the severity
      of fungal keratitis in a rabbit model and should be considered effective
      treatment alternatives in the therapy of Aspergillus fumigatus keratitis.

PMID- 12815531
TI  - Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits.
AB  - PURPOSE: Nitric oxide (NO) may control intraocular pressure (IOP)-regulating
      mechanisms physiologically and in ocular diseases such as glaucoma. The aim of
      the present study was to clarify whether an increase in aqueous humor outflow
      facility could explain the IOP-lowering effect of the NO/cyclic GMP pathway we
      recently described. METHODS: Test compounds were administered to anesthetized
      rabbits (New Zealand White, n = 6) intracamerally (5 microl) in the following
      doses: nitrosocaptopril 12.3 microg, captopril 10.9 microg, sodium nitroprusside
      (SNP) 13.1 microg and 8-Br-cGMP 22.3 microg. Outflow facility (C) was determined
      by the two-level constant pressure infusion method. Outflow facility, C( 1) and
      C(2), was measured at lower and higher pressure levels, respectively. RESULTS:
      Outflow facility was increased after treatment with SNP (increase in C in the
      experimental eye as compared to the control eye C( 1) 80% and C(2) 74%),
      nitrosocaptopril (C(1) 69% and C(2) 64%) and 8-Br-cGMP (C(1) 35% and C(2) 33%).
      Captopril had no effect on outflow facility (C(1) -12% and C(2) 2%). Blood
      pressure was not affected by the drugs. CONCLUSIONS: We conclude that enhancement
      of outflow facility by nitrosocaptopril, SNP and 8-Br-cGMP, their second
      messenger derivative, at least partly explains the IOP-lowering effect of NO
      releasing compounds.

PMID- 12815533
TI  - Scientific excellence, professional virtue, and the profit motive: the market and
      health care reform.

PMID- 12815532
TI  - Identification of transplanted retinal pigment epithelium with a novel
      chromosomal marker.
AB  - PURPOSE: To demonstrate the ability of a novel chromosomal marker to identify
      retinal pigment epithelium (RPE) after xenotransplantation, and determine the
      short-term correlation between pigment and this nuclear marker. METHODS: Primary
      pigmented RPE harvested from third trimester fetal pigs were transplanted as
      microaggregates into the subretinal space of 3 albino rabbits. We then used an in
      situ probe for a repetitive segment of the porcine chromosome to identify the
      transplanted RPE. RESULTS: Pigmented cells were visible in the subretinal space 2
      weeks after transplantation. Approximately 70% of pigment-containing cells were
      also labeled with the porcine chromosomal marker. Labeled cells were
      predominantly flatter in morphology and close to Bruch's membrane whereas
      unlabeled cells were rounder and further from Bruch's membrane. The outer nuclear
      layer thickness was normal above the pigmented monolayer but was decreased over
      areas containing multiple layers of pigmented cells. CONCLUSIONS: Fetal porcine
      RPE xenografts can be identified with a nuclear marker for a repetitive segment
      of the porcine chromosome. The presence of pigment within unlabelled cells
      suggests that pigment is not a robust marker for transplanted RPE.

PMID- 12815534
TI  - How compatible are liberty and equality in structuring a health care system?
AB  - In their normative role in shaping the basic structure of a health care system,
      liberty and equality are often thought to conflict so sharply that health policy
      is condemned to remain an ideological battleground. In this paper, I will
      articulate my own view of why much of the apparently fundamental conflict between
      individual liberty and responsibility, on the one hand, and equality and
      equality's related concern for cost-efficiency, on the other hand, is less
      intractable than it is usually assumed to be. The result will be to break the
      rigid and stereotypical association of liberty-emphasizing social philosophies
      with the pluralistic market paradigm for a health care system and egalitarian,
      equity-emphasizing social philosophies with the unitary public system paradigm.
      Understanding better the moral ingredients of liberty and equitable distribution
      as well as the complexity of how liberty and equality actually intersect in a
      health care system opens the door to seeing the possibility of significant
      reconciliation. I will conclude, among other things, that even semi-libertarian
      views of distributive justice should strongly embrace compulsory, universal
      coverage of health care for some significant level of care, and that egalitarian
      views ought not to regard different levels of coverage for people of different
      income levels as necessarily unjust.

PMID- 12815535
TI  - The British National Health Service: lessons from the "Socialist Calculation
      Debate".
AB  - The "Socialist Calculation Debate" is little known outside the economics
      profession, yet this inter-war debate between liberal and socialist economists on
      the practical feasibility of socialism has important implications for all
      contemporary public sector bureaucracies. This article applies the Mises-Hayek
      critique of central planning that emerged from this debate to the crisis
      presently facing the British National Health Service. The Mises-Hayek critique
      suggests that the UK government's plan for a renewal of the National Health
      Service will fail because of the epistemological pathologies that face any
      centrally planned system. It is argued that the key lesson of the Socialist
      Calculation Debate is that market prices and private property rights are
      essential for the efficient allocation of resources and the attainment of the
      best possible health outcomes.

PMID- 12815536
TI  - On the possibility of a positive-sum game in the distribution of health care
      resources.
AB  - Health care resource distribution is a subject of debate among health policy
      analysts, economists, and philosophers. In the United States, there is a widening
      gap between the more- and less-advantaged socioeconomic sub-populations in terms
      of both health care resource distribution and outcomes. Conventional wisdom
      suggests that there is a tradeoff, a zero-sum game, between efficiency and
      fairness in the distribution of health care resources. Promoting fairness in the
      distribution of health care resources and outcomes is not efficient in terms of
      maximization of a health outcome production function. On the other side of the
      coin, improving efficiency comes at the expense of fairness. Such conventional
      wisdom is supported in part by standard static Paretian welfare analysis.
      However, in this paper it is shown that in a dynamic setting in which there are
      efficiency gains in the health production function, fairness in distribution of
      health care resources can improve simultaneously.

PMID- 12815537
TI  - Holding civic medicine accountable: will Morreim's liability scheme work in a
      disaster?
AB  - In Holding Health Care Accountable, E. Haavi Morreim differentiates between
      duties of expertise and resource duties, arguing for tort liability respecting
      the former and contract liability respecting the latter. Though Morreim's book
      addresses ordinary clinical medicine, her liability scheme may also be relevant
      elsewhere. Focusing on disaster medicine, and especially the medical management
      of violent mass disasters (e.g., where terrorists have deployed weapons of mass
      destruction), I argue in this essay that Morreim's classification of duties still
      fits, but that it is difficult to hold government powers accountable for their
      many resource and expertise duties. This difficulty is compounded by political
      arrangements that foist under-funded mandates for disaster services on healthcare
      providers. As a result of such arrangements, hospitals and clinicians are prone
      to liability for expenditures and clinical interventions that are beyond their
      scope. This problem can be mitigated, I argue, by examining and clarifying the
      apparent social compact between society and healthcare.

PMID- 12815539
TI  - Traditional medicines in modern societies: an exploration of integrationist
      options through East Asian experience.
AB  - Modern scientific medicine is increasingly challenged by complementary and
      alternative therapies. Reviewing policy options for contemporary healthcare
      development, the World Health Organization's first global strategy on traditional
      and alternative medicine, released in May 2002, advocates integration. However,
      experience in East Asia, the only part of the world where state of the art modern
      scientific facilities are commonly found alongside thriving traditional
      practices, reveals that medical integration can take several forms. To clarify
      the available policy options, this article categorizes those forms, identifying
      three types of integration (unification, equalization and subjugation), plus one
      type of non-integration (marginalization). It marks out a zone of balanced
      healthcare development that cuts across two of the integrationist types, and
      comprises non-discriminatory state treatment of separate but linked sectors of
      traditional and modern medicine. The article closes by exploring arguments for
      and against locating state policy in this zone, and holds that policy should be
      situated here for medical practices that can meet broadly acceptable professional
      standards, demonstrate an existing social demand, and generate an adequate supply
      of medical practitioners, possibly through some state subsidy.

PMID- 12815542
TI  - A potential role for CXCR3 chemokines in the response to ocular HSV infection.
AB  - Corneal infection with herpes simplex virus (HSV) leads to the recruitment of
      immune cells to the eye itself, the trigeminal ganglion and the brainstem. In
      addition, some resident cells in these target tissues are infected by HSV,
      activated during the inflammatory response or both. Chemokine signaling is an
      important component of the regulatory circuit governing the host immune response
      to virus infection. This review discusses chemokine responses in relation to HSV
      infection of the cornea emphasizing the role of CXCR3 chemokine signaling by the
      IFN-gamma inducible ligands MIG, IP10 and I-TAC and includes discussion of their
      potential role in immunopathology in the nervous system.

PMID- 12815543
TI  - Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion,
      antiviral activity and transport across rabbit cornea.
AB  - PURPOSE: A series of dipeptide prodrugs of antiviral nucleoside acyclovir (ACV)
      were designed to target the oligopeptide transporter on the cornea with an aim of
      improving the ocular bioavailability and therapeutic activity of ACV. METHODS:
      Aqueous stability, ocular bioreversion kinetics in various tissues, in vitro
      antiviral activity, cell proliferation assay and corneal transport
      characteristics of the dipeptide prodrugs were studied. Results. ACV dipeptide
      prodrugs were found to be more stable at pH 5.6 in comparison to L-Val-ACV, an
      amino acid prodrug of ACV. The prodrugs exhibited higher solubility than ACV. Val
      Val-ACV and Val-Tyr-ACV were found to have excellent antiviral activity against
      herpes simplex virus-1 (HSV-1). All the dipeptide prodrugs exhibited lower
      cytotoxicity as compared to currently approved anti-HSV agent, trifluorothymidine
      (TFT). Transport of [(3)H] Val-ACV was inhibited significantly in the presence of
      the dipeptide prodrugs of ACV. Corneal permeabilities of all the ACV dipeptide
      prodrugs were observed to be higher than ACV possibly due to recognition of the
      prodrugs by the oligopeptide transporter on the cornea. CONCLUSIONS: The
      dipeptide prodrugs were found to be more permeable than the parent drug, ACV.
      More permeable, less cytotoxic ACV dipeptide prodrugs exhibited excellent
      chemical stability and antiviral activity against herpes simplex virus thereby
      rendering these lead compounds promising drug candidates against herpes virus
      infections.

PMID- 12815544
TI  - A novel apoptotic interaction between HSV-1 and human corneal epithelial cells.
AB  - PURPOSE: Herpes simplex virus type 1 (HSV-1) infects the cornea possibly causing
      blindness. The specific mechanisms of herpetic keratitis are unclear. We aimed to
      investigate whether HSV-1 would up- or down-regulate the apoptotic pathway of
      human corneal epithelial (HCE) cells. METHODS: HSV-1 infection of HCE and Vero
      cells was demonstrated (immunofluorescence) and apoptotic gene expression was
      quantified (ribonuclease protection assay). Caspase 8 protein activity
      (colorimetric assay) was quantified and compared to caspase 8 mRNA amounts from
      RPA experiments. The apoptotic index of HSV-1 infected HCE and Vero cells
      (apoptotic index = % of apoptotic cells in infected samples/mock treated samples)
      was obtained and compared to gene expression. RESULTS: A down-regulation in
      apoptotic gene expression was observed in HSV-1 infected HCE cells in contrast to
      Vero cells (infected and mock treated). Caspase 8 protein levels mirrored caspase
      8 mRNA levels in HSV-1 infected HCE cells. The apoptotic index also supports this
      down-regulation. HSV-1 infected human corneal epithelial cells and Vero cells at
      similar rates. CONCLUSION: HSV-1 down-regulates the apoptotic pathway of human
      corneal epithelial cells. This down-regulation of apoptotic gene expression seems
      to be cell specific. Also infectivity is excluded in playing a role in regulation
      of the apoptotic pathway because HSV-1 replicated at similar rates in HCE and
      Vero cells.

PMID- 12815545
TI  - Functional expression of a sodium dependent nucleoside transporter on rabbit
      cornea: Role in corneal permeation of acyclovir and idoxuridine.
AB  - PURPOSE: The major objectives were to investigate functional expression of
      nucleoside transporters on the rabbit cornea and to delineate mechanism of
      corneal permeation of acyclovir (ACV) and idoxuridine (IDU). Methods. Transport
      studies were conducted with isolated rabbit corneas at 34 degrees C using
      [(3)H]thymidine, [(3)H]ACV and [(3)H]IDU. RESULTS: Thymidine transport across
      rabbit cornea comprised of saturable (K(m) = 14.9 +/- 9.7 microM and V(max) =
      0.045 +/- 0.0087 nmol/min) and non saturable (k(d) = 0.00015 +/- 0.000013
      microl/min) components. Both purine and pyrimidine nucleosides including inosine
      inhibited transport of [(3)H]thymidine. However, nucleobases adenine and thymine
      did not have any inhibitory effect on thymidine transport which was sodium
      dependent with a Na(+): thymidine coupling ratio of greater than 1 : 1 indicating
      that the nucleoside transporter is of the N3 type. Although IDU inhibited
      transport of [(3)H]thymidine, unlabeled IDU and thymidine did not inhibit
      [(3)H]IDU transport suggesting that IDU was binding to the transporter but was
      not translocated by it. ACV did not affect transport of [(3)H]thymidine.
      Moreover, thymidine, adenine or unlabeled ACV did not inhibit [(3)H]ACV
      transport. Permeability coefficients of ACV and IDU over a 4 fold concentration
      range did not show any significant difference confirming that these antiviral
      agents permeate the cornea by passive diffusional mechanism. CONCLUSION:
      Functional expression of a N3 type sodium dependent nucleoside transporter has
      been demonstrated on the rabbit cornea. Antiviral nucleoside analogs ACV and IDU
      are not substrates for this transporter and appear to permeate the cornea by
      simple passive diffusion.

PMID- 12815546
TI  - Effect of immunization on herpes simplex virus type 1 latent infection in the
      trigeminal ganglion.
AB  - PURPOSE: To quantify and characterize immune protection from herpes simplex virus
      (HSV) latent infection in mice following corneal challenge. METHODS: Mice
      immunized or mock-immunized and boosted in the flank with an HSV replication
      deficient mutant were challenged by corneal inoculation with wild type (wt) or
      thymidine kinase-negative (TK(-)) HSV. At specified times post challenge,
      trigeminal ganglia were assayed for in vitro reactivation, latent and acute viral
      load (using quantitative PCR), acute infection, and cellular infiltration
      (hematoxylin and eosin stained sections). RESULTS: With wt HSV challenge
      infection, immunization led to reduced reactivation, significantly less latent
      and acute viral DNA, and no acute viral replication in ganglia, and rapid
      infiltration of inflammatory cells. Immunization had little effect on viral load
      following challenge with replication-conditional TK(-) mutant virus. CONCLUSION:
      These results indicate that immune protection from latent HSV infection in mouse
      trigeminal ganglia following ocular infection can act under these experimental
      conditions to block acute viral replication in ganglia and is directed to
      antigenic targets within the ganglia.

PMID- 12815547
TI  - Apoptosis and increased expression of Fas ligand after uniocular anterior chamber
      (AC) inoculation of HSV-1.
AB  - PURPOSE: To determine if apoptosis occurs in the eyes and brain following
      uniocular anterior chamber (AC) inoculation of HSV-1 and if expression of Fas
      ligand (FasL) or Fas is altered by virus infection. METHODS: After inoculation of
      HSV-1 via the AC route, apoptotic cells in the eyes and brain were identified by
      TUNEL assay, and TUNEL results indicating DNA fragmentation in the brain were
      confirmed by DNA laddering assays. Expression of FasL and Fas in the eyes and
      brain was determined by immunohistochemistry and Western blotting and confirmed
      by RT-PCR, Southern blotting of RT-PCR products, and sequencing. RESULTS: After
      AC inoculation of HSV-1, HSV-1 positive cells and apoptotic cells were observed
      in the eyes and brain. Immunofluorescent staining revealed that although both
      FasL and Fas were expressed in the cornea, retinal pigment epithelium cells
      (RPE), and photoreceptor cells of normal and virus infected mice, Fas and FasL
      were expressed at different locations in these cells. On day 8 p.i., more FasL
      DNA expression was observed in HSV-infected mice compared with uninfected mice.
      CONCLUSIONS: HSV-1 infection following AC inoculation of virus induced apoptosis
      in the eyes and brain. Although FasL expression was upregulated by HSV-1
      infection, these results suggest there are likely to be factors in addition to
      FasL and Fas, such as Bcl-2 and caspases, that are involved in apoptosis observed
      in the eyes and brain of HSV-1-infected mice.

PMID- 12815548
TI  - Ocular reactivation phenotype of HSV-1 strain F(MP)E, a corticosteroid-sensitive
      strain.
AB  - PURPOSE: Elucidate the ocular reactivation of HSV-1 strain F(MP)E. METHODS:
      Rabbit corneas were infected with HSV-1 strains McKrae and F(MP)E. Latency was
      established and rabbits were treated with epinephrine iontophoresis or
      corticosteroid injection (immunosuppression). Cultured tear films were used to
      determine the presence of infectious virus. Eyes of immunosuppressed rabbits were
      also examined by slit lamp biomicroscopy. Trigeminal ganglia were co-cultured on
      indicator cells at time of sacrifice for detection of virus. Quantitative real
      time PCR was used to detect the number of viral genome copies in the trigeminal
      ganglia. RESULTS: Acute infections by strains McKrae and F(MP)E were the same.
      Ocular reactivation of strain F(MP)E by epinephrine iontophoresis was
      significantly reduced compared to McKrae (P </= 0.0001), but was not
      significantly different from McKrae after corticosteroid injection (P > 0.29).
      Slit lamp examination following corticosteroid injection showed a correlation of
      recurrent herpetic lesions with infectious virus in tear film swabs for both
      McKrae and F(MP)E. Trigeminal ganglia from rabbits latently infected with each
      strain and each method of induced reactivation resulted in infectious virus (P
      >/= 0.69). Genome copies for both strains were present and were highly variable.
      CONCLUSIONS: HSV-1 strain F(MP)E has low reactivation following epinephrine
      iontophoresis compared to McKrae, but has high reactivation like McKrae in
      response to corticosteroids. The difference in reactivation following epinephrine
      iontophoresis is not due to a difference in the establishment of latency.

PMID- 12815550
TI  - An HSV-1 chimeric containing HSV-2 latency associated transcript (LAT) sequences
      has significantly reduced adrenergic reactivation in the rabbit eye model.
AB  - PURPOSE: Both HSV-1 and HSV-2 express LAT during viral latency. Previous studies
      indicated that deletion of either LAT impairs viral reactivation from latency,
      but that the HSV-1 LAT confers the ability to reactivate efficiently from
      trigeminal ganglia onto HSV-2. We sought to determine whether the HSV-2 LAT could
      function in the context of HSV-1. METHODS: A chimeric HSV-1 that expresses the
      HSV-2 LAT in place of both copies of its own LAT was constructed. A rescuant
      virus, in which the wild-type genotype was restored, was also constructed to
      demonstrate that any phenotypic differences between the mutant virus and wild
      type virus were due to the introduced mutations rather than to inadvertent
      mutations elsewhere in the virus. All viruses were tested in vitro and in vivo
      (via inoculation of rabbit eyes and induction of reactivation via iontophoresis
      of epinephrine) to determine the ability of the HSV-2 LAT to substitute for the
      HSV-1 LAT during acute infection and reactivation from latency. RESULTS:
      Substitution of the HSV-2 LAT for the HSV-1 LAT had no effect on acute
      replication or on the ability of the virus to cause disease in the rabbit ocular
      model. The ability of the mutant virus to reactivate from latency was
      substantially impaired relative to wild-type HSV-1. CONCLUSIONS: The HSV-2 LAT
      cannot substitute for the HSV-1 LAT in promoting reactivation from HSV-1 latency
      from rabbit trigeminal ganglia. This is consistent with the LAT being the major
      determinant of site-specific HSV reactivation.

PMID- 12815549
TI  - Murine cytomegalovirus retinitis during MAIDS: Susceptibility correlates with
      elevated intraocular levels of interleukin-4 mRNA.
AB  - PURPOSE: To determine if murine cytomegalovirus (MCMV)-infected eyes of mice with
      murine acquired immunodeficiency syndrome (MAIDS) that are destined to develop
      MCMV retinitis display elevated intraocular levels of interleukin-4 (IL-4) mRNA
      when compared with uninfected eyes of mice with MAIDS and unmanipulated,
      uninfected, eyes of normal healthy mice. METHODS: Groups of C57BL/6 mice with
      MAIDS and normal C57BL/6 mice were infected uniocularly with MCMV by subretinal
      MCMV injection. IL-4 levels in individual spleens collected five days later from
      groups of MAIDS mice and normal mice were assessed by quantitative ELISA. MCMV
      infected eyes and uninfected contralateral eyes from another group of mice with
      MAIDS were also collected at five days postinfection and individually subjected
      to competitive RT-PCR assay and real-time RT-PCR assay for detection and
      quantification of IL-4 mRNA. Unmanipulated eyes from normal C57BL/6 mice served
      as controls. RESULTS: IL-4 mRNA was detected at a level of 9.7 +/- 3.4 pg mRNA
      per 1000 ng total RNA in 100% of MCMV-infected eyes of mice with MAIDS by
      competitive RT-PCR assay, but could not be detected in any of the uninfected eyes
      of MAIDS mice. In comparison, the more sensitive technique of real-time RT-PCR
      assay detected copies of IL-4 cDNA in both MCMV-infected eyes and uninfected eyes
      of MAIDS mice. MCMV-infected eyes showed a 16-fold increase in the number of IL-4
      cDNA copies when compared with uninfected eyes. Neither technique detected IL-4
      mRNA in unmanipulated eyes of normal mice. As expected, spleen cells from mice
      with MAIDS expressed significantly greater levels of IL-4 when compared with
      spleen cells from normal mice. CONCLUSIONS: MCMV-infected mice with MAIDS
      exhibited an expected preferential activation of Th2 cells as determined by
      increased levels of IL-4 in spleen cells when compared with spleen cells of
      normal mice. MCMV-infected eyes destined to develop retinitis during MAIDS also
      showed increased levels of detectable IL-4 mRNA when compared with uninfected
      eyes of mice with MAIDS. It is therefore possible that IL-4 synthesis by Th2 CD4+
      T cells during retrovirus-induced immunosuppression serves to inhibit the
      perforin cytotoxic pathway that subsequently allows susceptibility to MCMV
      retinitis during MAIDS.

PMID- 12815551
TI  - Changes in gene expression in latent HSV-1-infected rabbit trigeminal ganglia
      following epinephrine iontophoresis.
AB  - PURPOSE: The aim of the present study was to identify the genes that express in
      the nervous system when herpes simplex virus type 1 (HSV-1) reactivates from
      latency by using subtraction cloning following epinephrine iontophoresis.
      METHODS: The corneas of New Zealand White rabbits (2 to 2.5 kg) were topically
      inoculated with 5 x 10(5) PFU of plaque-purified HSV-1 strain McKrae. Corneal
      infection was monitored by slit lamp examination (SLE) on days 3-7 after
      infection. At 30 d post-infection, eyes were assessed for infectious virus by
      ocular swabs. Disappearance of virus in ocular swabs signified latency for HSV-1.
      Latently-infected rabbits were subjected to transcorneal iontophoresis. The
      messenger RNA (mRNA) was isolated from the trigeminal ganglia and used for
      subtraction cloning and subtraction library synthesis. RESULTS: Our results
      indicate 18 genes with increased expression and 6 genes with decreased levels.
      Northern blot analysis revealed that genes for OX-40 ligand, MHC class II HLA-DR
      alpha and beta-microglobulin showed predominant increase followed by tyrosine 3'
      monooxygenase, proteolipid protein, tyrosine beta, and apolipoprotein D. Genes
      that underwent reduced expression included cytochrome c oxidase subunit I, ATP
      synthase isoform, cytochrome b, ATPase 9, and at least one unidentified gene.
      CONCLUSIONS: Our results, particularly the increased detection of OX-40 ligand
      and MHC class II-alpha and beta-2 microglobulin, support the finding that
      lymphocytes persist in latently-infected trigeminal ganglia (TGs). These results
      also suggest a role of the immune system in HSV-1 recurrences. In addition, we
      have detected genes associated with neuronal disorders, OX-40L, proteolipid
      protein, and apolipoprotein D.

PMID- 12815552
TI  - Gene expression profiling in the HSV-1 latently infected mouse trigeminal ganglia
      following hyperthermic stress.
AB  - PURPOSE: To assess gene expression in herpes simplex virus type 1 (HSV-1) latent
      mouse trigeminal ganglia (TG) at 6 and 24 hours after hyperthermic stress.
      METHODS: Uninfected and HSV-1 latently infected mice were heat stressed (43
      degrees C, 10 min). TG from six groups of mice were studied: 1) uninfected, not
      stressed, 2) uninfected, heat-stressed, sacrificed at 6 hours after hyperthermia,
      3) uninfected, heat-stressed, sacrificed at 24 hours after hyperthermia, 4)
      latently infected, not stressed, 5) latently infected, heat-stressed, sacrificed
      at 6 hours after hyperthermia, 6) latently infected, heat-stressed, sacrificed at
      24 hours after hyperthermia. Poly A(+) mRNA from the TG of each group of mice was
      reverse transcribed, labeled with (32)P, and incubated on a nylon gene array
      membrane. The genes showing the largest signal-to-control changes (varying by a
      factor of at least 1.27-fold) were considered to have undergone significant
      change in expression. RESULTS: Six hours after heat stress the genes whose
      expression was altered included the FK506-binding protein gene (decreased), the T
      complex protein 1 alpha subunit gene (increased), and the 94-kDa glucose
      regulated protein gene (increased in uninfected TG, decreased in infected TG).
      Heat stress increased expression of the DNA excision repair protein ERCC5 gene 24
      hours after the treatment. Genes previously reported to exhibit increased
      transcription 1 hour after stress did not continue to show significant
      transcriptional activation at 6 or 24 hours. CONCLUSION: Altered gene expression
      at 6 and 24 hours after heat stress was different from previously reported
      changes in gene expression 1 hour after hyperthermia in HSV-1 latently infected
      mice.

PMID- 12815553
TI  - Herpesvirus quiescence (QIF) in neuronal cells VI: Correlative analysis
      demonstrates usefulness of QIF-PC12 cells to examine HSV-1 latency, reactivation
      and genes implicated in its regulation.
AB  - PURPOSE: To compare the usefulness of the in vitro quiescently infected (QIF)
      PC12 cell model(30) with the in vivo rabbit eye model of latency for the study of
      herpes simplex virus (HSV) genes implicated in reactivation from latency.
      METHODS: HSV-1 strains 17+/pR20.5/5 and 17+/pR20.5/5/LAT, that were previously
      constructed by insertion of genes encoding beta-galactosidase, green fluorescent
      protein (GFP) or the latency associated transcript (LAT) open reading frame in
      the U(S)5 region,(34) were used to examine viral growth and inducible
      reactivation in the two models. RESULTS: 17+/pR20.5/5 exhibited diminished
      reactivation phenotype when compared with wild type 17+ in neuronal cells (i.e.,
      QIF-PC12 cell model) and the rabbit eye model of latency. 17+/pR20.5/5/LAT, which
      contains the deregulated LAT gene, reactivated at wild type levels. Analysis of
      growth in neurally differentiated (ND)-PC12 cells demonstrated a low proportion
      of QIF cells expressed virus-encoded signals during the quiescent infection and a
      direct relationship between lytic viral growth in neuronal cells and reactivation
      phenotype. Even though 17+/pR20.5/5/LAT produced a more severe acute infection in
      the rabbit cornea, the different reactivation efficiency of 17+/pR20.5/5 and
      17+/pR20.5/5/LAT in vivo and in vitro was not attributed to different viral
      genome copy number in the cells harboring cryptic genomes. CONCLUSIONS: We
      conclude that 1) viral growth in neuronal cells correlates with reactivation
      phenotype in vivo and in vitro, 2) 17+/pR20.5/5 is attenuated in viral growth and
      reactivation in both models, and 3) 17+/pR20.5/5/LAT demonstrates wild-type
      phenotype for reactivation in both models. Attenuation of 17+/pR20.5/5 could be
      the result of the disruption of U(S)5 or a second site mutation. If the
      attenuation is the result of U(S)5 disruption, a gene that provides anti
      apoptotic functions,( 41,42) this attenuation is more than compensated for by the
      expression of the LAT ORF. Overall, the findings indicate that the QIF-PC12 cell
      model is useful for segregating phases of reactivation, and particularly studying
      the inductive events involved in reactivation of a cryptic viral genome in
      neurally differentiated cells.

PMID- 12815554
TI  - Tolerance of efavirenz-induced central nervous system side effects in HIV
      infected individuals with a history of substance abuse.
AB  - PURPOSE: There is no published data looking at tolerance of efavirenz (EFV) in
      patients who abuse cocaine or alcohol (EtOH). The objective of this study was to
      determine whether individuals with a current or past history of cocaine or EtOH
      abuse are more likely to experience EFV-induced central nervous system (CNS) side
      effects that warrant discontinuation of EFV compared with those who do not abuse
      substances. METHOD: Retrospective chart review of all patients who received a
      nonnucleoside reverse transcriptase inhibitor (NNRTI) at an inner city Ryan White
      Title III-supported health clinic during 1992-2001. RESULTS: During the study
      period, 99/279 (78% African American, 88% male) patients were prescribed an
      NNRTI. Patients on an NNRTI with either a history of or current substance abuse
      (SA) abused cocaine (30%), EtOH (70%), or marijuana (33%). Of these, 38% abused
      more than one substance. There were 39/63 EFV patients who were substance abusers
      compared with 16/36 patients not on EFV who were substance abusers (p =.09).
      Examining patients on EFV, 6/24 with SA and 7/39 without SA reported a CNS side
      effect (p =.54). Among patients on EFV, 4/24 with SA versus 13/39 without SA
      reported stopping EFV (p =.24). CONCLUSION: SA did not have a significant effect
      on patients' ability to remain on EFV. Patients who abused cocaine or EtOH or
      smoked marijuana were at no more risk of exhibiting CNS side effects than those
      who denied a history of substance abuse.

PMID- 12815555
TI  - Oxymetholone for the treatment of HIV-wasting: a double-blind, randomized,
      placebo-controlled phase III trial in eugonadal men and women.
AB  - BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic
      involuntary weight loss still remains a serious problem in the care of HIV
      patients due to various alterations in energy metabolism and endocrine
      regulation. Previous studies in HIV-positive men undergoing androgen replacement
      therapy or treatment with recombinant growth hormone (rGH) have shown partial
      restoration of lean body mass (LBM), but these treatments have largely not been
      sufficiently studied in eugonadal individuals. METHOD: A double-blind,
      randomized, placebo-controlled trial of 89 HIV-positive eugonadal women and men
      with wasting assigned to the anabolic steroid oxymetholone (50 mg bid or tid) or
      placebo for 16 weeks was performed. Body weight, bioimpedance measurements,
      quality of life parameters, and appetite were analyzed. RESULTS: Oxymetholone led
      to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the tid and bid
      groups, respectively (p <.05 for each treatment versus placebo), while
      individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell
      mass (BCM) increased in the oxymetholone bid group (3.8 +/- 0.4 kg; p <.0001) and
      in the oxymetholone tid group (2.1 +/- 0.6 kg; p <.005). Significant improvements
      were noted in appetite and food intake, increased wellbeing, and reduced weakness
      by self-examination. The most important adverse event was liver-associated
      toxicity. Overall, 43% of patients in the tid group, 25% of patients in the bid
      oxymetholone group, and 8% in the placebo group had a greater than 5 times
      baseline increase for ALT, AST, or gamma GT, while other adverse events were not
      increased over placebo. CONCLUSION: Oxymetholone can be considered an effective
      anabolic steroid in eugonadal male and female patients with AIDS-associated
      wasting. The bid (100 mg/day) regimen appeared to be equally effective to the tid
      (150 mg/day) regimen in terms of weight gain, LBM, and BCM and was associated
      with less liver toxicity.

PMID- 12815556
TI  - Attenuated T-lymphocyte response to HIV therapy in individuals receiving HMG-CoA
      reductase inhibitors.
AB  - PURPOSE: The protease inhibitor class of antiretroviral agents is associated with
      the unwanted side effect of hypertriglyceridemia, which is usually treated with
      either HMG-CoA reductase inhibitors (statins) or fibrates. However, since statin
      therapy is intrinsically immunomodulatory, we questioned whether the T-cell
      response of patients who received PI-based therapy plus statin differed from the
      response of patients on PI therapy alone or on PI therapy with a fibrate. METHOD:
      Retrospective cohort study. RESULTS: Thirty-five patients who had received
      ritonavir/saquinavir (R/S)-based antiretroviral therapy for 5 or more years were
      evaluated and stratified into four treatment groups: patients on R/S alone (n =
      9), patients on R/S and stavudine/lamivudine (d4T/3TC) (n = 10), patients on R/S
      with or without d4T/3TC and statin (n = 11), or patients on R/S with or without
      d4T/3TC and fibrate (n = 5). All patients had suppressed levels of viral
      replication at all time points. T-cell responses were similar in all four groups
      before they were exposed to lipid-lowering agents. After the addition of lipid
      lowering agents, absolute CD4 T-cell responses were lower in the statin group
      than in all other groups (p <.05), when measured after 6, 12, and 18 months of
      treatment. CONCLUSION: These data suggest that T-cell responses are influenced by
      the choice of anti-lipid agent and suggest that a prospective comparison is
      needed to determine the clinical relevance of these findings.

PMID- 12815557
TI  - An in vivo pharmacokinetic/pharmacodynamic model for antiretroviral combination.
AB  - PURPOSE: The objective of this study was to investigate the
      pharmacokinetic/pharmacodynamic properties of an antiretroviral therapy in HIV
      infected patients. METHOD: Eight HIV-infected patients received zidovudine,
      lamivudine, and indinavir as their first antiretroviral treatment.
      Pharmacokinetic data were analyzed separately using a one-compartmental model
      with first-order absorption, and the individual estimates were used to simulate
      drug concentrations. To determine the relationship between drug concentrations
      and the antiviral effect, an in vitro E(max) model was tested. Alternatively, a
      dynamic model was built describing the viral and cellular pathophysiology,
      including the turnover of viral replication in infected cells and the production
      of virus under treatment. RESULT: The E(max) model fit poorly the experimental
      data. The complex model was not identifiable with the data available in this
      study, however a simplified model allowed us to estimate the pharmacodynamic
      parameters reflecting the decrease of both infected cells and viral load under
      antiretroviral treatment. CONCLUSION: Using potent highly active antiretroviral
      therapy, the treatment was so effective that it was not possible to estimate the
      parameters of the relationship between drug concentrations and the reduction of
      viral load. Even if the relationship does exist, the direct response model of
      antiretroviral agents cannot be demonstrated, however the simplified model
      provides an understanding of the synergy of such a combination and offers
      suggestions as how to prevent the emergence of viral resistant strains.

PMID- 12815559
TI  - Once-a-day HAART: dream or reality?
AB  - A constant and nearly absolute adherence is required to ensure a successful long
      lasting outcome of highly active antiretroviral therapy (HAART). Pill burden and
      regimen complexity are important contributors to adherence problems. The most
      significant treatment-related strategy to improve adherence may be the reduction
      in the number and frequency of pills to be taken every day. If one accepts the
      concept that once-daily therapy is likely to benefit patients, then the issue
      turns to whether we have adequate drugs to implement once-daily HAART. There is
      quite a difference between using a once-a-day drug within an HAART regimen and
      designing an HAART regimen that is dosed once daily. To date, studies that
      explore the feasibility of once-a-day HAART regimens are still few, mostly
      exploratory, not controlled, and performed in a limited number of patients.
      However, most data are consistent one with the other, and evidence on the utility
      of such regimens is growing. Once-daily therapy cannot be the answer to all the
      questions that complex and life-long therapies give rise to, but it could be a
      further choice that can meet the needs of many patients. The range of once-daily
      options is expanding rapidly, and the patients' request for easier therapies that
      are respectful of their lifestyle could be fulfilled.

PMID- 12815558
TI  - HIV-positive immigrants in the Canary Islands, Spain: implications for public
      health in Europe.
AB  - BACKGROUND: The Canary Islands face the northwest coast of Africa and belong
      administratively to Spain. They represent a frequent step for the entrance of
      Africans into Spain and, from there, to all the European Union. The presence of
      HIV-1 non-B variants has already been reported in Spain and other European
      countries, mostly among African immigrants. PURPOSE: The aim of this study was to
      exam the genetic diversity of HIV-1 among immigrants attending a reference
      hospital in the Canary Islands during 2000. METHOD: Phylogenetic analyses of the
      reverse transcriptase (RT), protease, and env genes were carried out in 33
      immigrants found to be HIV-1 positive. RESULTS: HIV-1 non-B subtypes were
      recognized in 21 (63.6%) of the 33 infected participants. Phylogenetic analyses
      showed non-B sequences in 60%, 60.6%, and 48.3% of specimens, depending on the
      genomic region examined (RT, protease, and env, respectively). Overall, 15
      viruses (45%) were found to be inter-subtype recombinants: AG in 8 (53%), GB in 4
      (27%), and AB in 3 (20%). CONCLUSION: Nearly two thirds of HIV-infected
      immigrants arriving to the Canary Islands carry non-B subtypes. Thus, the Canary
      Islands may be a frequent entry point for new HIV-1 variants into the European
      Union.

PMID- 12815560
TI  - Selected topics from the 10th Conference on Retroviruses and Opportunistic
      Infections.

PMID- 12815561
TI  - Once-daily saquinavir-hgc plus low-dose ritonavir (1200/100 mg) in HIV-infected
      pregnant women: pharmacokinetics and efficacy.

PMID- 12815563
TI  - A device is not a drug.

PMID- 12815562
TI  - A gene locus responsible for dyschromatosis symmetrica hereditaria (DSH) maps to
      chromosome 6q24.2-q25.2.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease
      characterized by the presence of hyperpigmented and hypopigmented macules on
      extremities and face. The gene, or even its chromosomal location, for DSH has not
      yet been identified. In this study, two Chinese families with DSH were identified
      and subjected to a genomewide screen for linkage analysis. Two-point linkage
      analysis for pedigree A (maximum LOD score [Z(max)] = 7.28 at recombination
      fraction [theta] = 0.00) and pedigree B (Z(max) = 2.41 at theta = 0.00) mapped
      the locus for DSH in the two families to chromosome 6q. Subsequent multipoint
      analysis of the two families also provided additional support for the DSH gene
      being located within the region 6q24.2-q25.2, with Z(max) = 10.64. Haplotype
      analysis confined the locus within an interval of 10.2 Mbp, flanked by markers
      D6S1703 and D6S1708. The two families had no identical haplotype within the
      defined region, which suggests that the two families were different in origin.
      Further work on identification of the gene for DSH will open new avenues to
      exploration of the genetics of pigmentation.

PMID- 12815564
TI  - Late breaking heart failure trials from the 2003 ACC meeting: EPHESUS and
      COMPANION.

PMID- 12815565
TI  - Effect of Valsartan on hospitalization: results from Val-HeFT.
AB  - BACKGROUND: Although current therapies have improved heart failure (HF) outcome,
      hospitalizations continue at high rates. The Valsartan Heart Failure Trial (Val
      HeFT) showed that valsartan reduced the risk of first worsening HF
      hospitalization by 27.5% versus placebo (P <.001). This article analyzes all
      cause and investigator-assessed HF hospitalization in Val-HeFT overall and in
      subgroups defined by preexisting HF therapy. METHODS: Val-HeFT was a randomized,
      double-blind parallel-arm study in which HF patients (New York Heart Association
      class II-IV) received either valsartan (n = 2511, force-titrated to 160 mg twice
      daily) or placebo (n = 2499) in addition to prescribed HF therapy. Total and per
      patient-year investigator-assessed hospitalizations (all-cause or HF) were
      analyzed according to prescribed therapy at baseline (angiotensin-converting
      enzyme inhibitors [ACEI] and beta-blockers [BB]). RESULTS: Hospitalization for
      worsening HF accounted for 35% of all hospitalizations. There were 2856 and 3106
      total all-cause hospitalizations in the valsartan and placebo groups,
      respectively, an 8% reduction (P =.145). Valsartan significantly reduced the
      overall number of investigator-assessed HF hospitalizations (-22.4%, P =.002) and
      reduced HF hospitalizations in the combination therapy subgroups (significant for
      ACEI+/BB- P =.003 and ACEI-/BB- P =.028) except those receiving both ACEI and BB.
      The benefit of valsartan versus placebo was more pronounced in reducing the
      number of patients with recurrent HF hospitalization (-20.6%) than single
      hospitalizations (-8.7%). CONCLUSIONS: Addition of valsartan to prescribed HF
      therapy demonstrated significant reductions in HF hospitalizations and was
      particularly beneficial in reducing recurrent HF hospitalization.

PMID- 12815566
TI  - Randomized Trial of Telephone Intervention in Chronic Heart Failure (DIAL): study
      design and preliminary observations.
AB  - BACKGROUND: In the last few years different approaches based on comprehensive
      patient care and close surveillance by multidisciplinary teams have shown
      promising results in heart failure. However, current evidence mainly derives from
      small and often nonrandomized studies performed at a single center, with selected
      populations, using dissimilar and complex strategies. We designed a large
      randomized study to test the hypothesis that a single program, based on a
      centralized telephone intervention performed by trained nurses, could reduce
      morbidity and mortality in chronic heart failure. METHODS: The Randomized Trial
      of Telephone Intervention in Chronic Heart Failure (DIAL) is a randomized,
      controlled, open trial designed to compare frequent telephone follow-up
      intervention versus control. We enrolled 1518 patients with stable chronic heart
      failure and optimal treatment from 51 centers in Argentina. DIAL trial
      intervention strategy is based on frequent telephone follow-up provided by nurses
      trained in heart failure and performed from a single surveillance center,
      assuring a homogeneous and high quality intervention. The primary objective is to
      determine the effect of the intervention as compared with the usual follow-up on
      the combined endpoint of all-cause mortality or hospitalization for worsening
      heart failure. The objectives of the intervention are education, counseling, and
      monitoring to enhance self-control mechanisms, timely medical visits, diet, and
      drug therapy compliance. Telephone call frequency was determined according to
      preestablished criteria of clinical status severity assessed at each phone
      contact. The study ended in August 2002. CONCLUSION: The results of this study
      may provide information about mortality, hospitalizations, and quality of life
      contributing to set standards for management programs in the current treatment of
      chronic heart failure.

PMID- 12815567
TI  - Care processes and clinical outcomes of continuous outpatient support with
      inotropes (COSI) in patients with refractory endstage heart failure.
AB  - BACKGROUND: This study describes the process and outcomes of continuous
      outpatient support with inotropes (COSI) in patients with Stage D heart failure
      (HF). Although Stage D HF has recently been defined as end-stage disease
      requiring special interventions for survival such as COSI or ventricular assist
      devices, concern has been raised regarding the safety, efficacy, mortality
      outcomes, and ethics of COSI. METHODS AND RESULTS: Inotrope dependence was
      defined as worsening of the patient's clinical status with attempted inotrope
      withdrawal such that the patient was deemed unlikely to survive to permit
      hospital discharge. A care process for COSI was designed; baseline and outcome
      variables were evaluated. COSI was administered to 36 inotrope-dependent patients
      (age 55.4 +/- 9.5 years, 24 males). Baseline characteristics (mean +/- SD) were
      consistent with Stage D HF: left ventricular ejection fraction 19.9 +/- 8.5, left
      ventricular end-diastolic dimension (LVEDD) 70 +/- 10 mm, systolic blood pressure
      97.4 +/- 13.4 mm Hg, serum creatinine 1.5 +/- 0.6, serum sodium 131.7 +/- 5.3; 69
      HF hospitalizations (mean 1.9 +/- 1.8) 6 months before COSI initiation.
      Symptomatic hypotension, increasing dyspnea, renal dysfunction, and hypoperfusion
      most commonly prevented inotrope withdrawal. Despite Stage D HF, patients were
      discharged with COSI ambulatory, oriented, and pain free. Rehospitalizations were
      46; 6 subjects accounted for 24 hospitalizations; 23 had 0 or 1
      rehospitalization. Median survival was 3.4 months (range 0.2-26.3 months); and 3
      , 6-, and 12-month Kaplan Meier survival was 51%, 26%, and 6%, respectively. The
      majority of patients died at home and chose to not undergo resuscitation
      attempts. CONCLUSION: COSI may be an acceptable treatment option for Stage D HF.

PMID- 12815568
TI  - The cul-de-sac at the end of the road.

PMID- 12815569
TI  - Survival and hospitalization in heart failure patients with or without diabetes
      treated with beta-blockers.
AB  - BACKGROUND: Physicians are still concerned about prescribing beta-blockers in
      diabetic patients with heart failure. METHODS: In the outcome research study (the
      Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical
      Practice [BRING-UP] study), the responsible clinicians could decide whether to
      start beta-blocker treatment and which agent to use. A total of 3091 patients
      were enrolled by 202 cardiologic centers: 25% of the recruited patients were
      already on beta-blockers, 28% started treatment at the enrollment visit, and 47%
      were not started on beta-blockers. RESULTS: The 1-year mortality, hospitalization
      rate, and the combined end point of mortality or hospitalization were higher in
      diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence
      intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11
      1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The
      event-free analysis of the 4 groups (diabetic patients not treated with beta
      blockers, diabetic patients treated with beta-blockers, nondiabetic patients not
      treated with beta-blockers, nondiabetic patients treated with beta-blockers)
      showed that patients treated with beta-blockers had a higher event-free
      probability than patients not treated with beta-blockers regardless the presence
      of diabetes (P <.0001). CONCLUSIONS: On the basis of post hoc analysis, diabetic
      patients with chronic heart failure benefit from beta-blockers even if at a lower
      degree. Thus, there are no justifications to avoid beta-blockers in heart failure
      patients in the presence of diabetes.

PMID- 12815570
TI  - Tolerability to beta-blocker therapy among heart failure patients in clinical
      practice.
AB  - BACKGROUND: Although beta-blockers were well-tolerated by heart failure (HF)
      patients in clinical trials, tolerability of these drugs in a general population
      of HF patients is not well-described. METHODS: We studied a total of 308
      encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects
      and frequency and predictors of discontinuation of therapy were studied.
      Independent predictors of discontinuation were assessed. RESULTS: Weight gain
      (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common
      side effects. Fifty-one patients (19%) were discontinued on therapy with any 1
      particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common
      reasons for discontinuation. Forty (78%) of these were given a trial with a
      different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker
      were tolerated. Thus the overall absolute discontinuation rate was only 7% for
      patients who were given a trial with different beta-blockers or 11% for the
      entire study population. Independent predictors of discontinuation of therapy
      included advanced symptoms, nonischemic etiology, history of pulmonary disease,
      and higher diuretic doses. CONCLUSION: Side effects with beta-blockers in a
      general population of HF patients are common; however, with changes in medical
      management, most patients can tolerate them eventually. In case of intolerance to
      one kind, a trial with a different beta-blocker is indicated.

PMID- 12815571
TI  - Prescription patterns of diuretics in chronic heart failure: a contemporary
      background as a clue to their role in treatment.
AB  - BACKGROUND: Diuretics are the cornerstone of treatment for the congestive
      symptoms of heart failure (HF). Despite their widespread use, diuretic
      prescription data in clinical practice are scarce. In this study we evaluated the
      prescription pattern of diuretics in a large population of HF outpatients,
      enrolled by a national network of hospital-based cardiologists. METHODS AND
      RESULTS: Among 11070 HF outpatients (mean age 64 +/- 12 years, 72.9% men, 29.8%
      New York Heart Association [NYHA] class III-IV, mean left ventricular ejection
      fraction [LVEF] 35+/-12%), 9247 took a diuretic, the most frequently prescribed
      therapeutic agent (83.5%). Loop diuretics were prescribed alone (65.5%) or
      combined with other diuretics in 91.6% of patients. By multivariate analysis, the
      strongest independent predictors of diuretic use were a previous hospital
      admission for HF (odds ratio [OR] 2.55, 95% confidence interval [CI] 2.28-2.86),
      NYHA class III-IV (OR 2.52, 95% CI 2.14-2.96), LVEF < 30% (OR 1.87, 95% CI 1.57
      2.24). Aldosterone antagonists were prescribed to 2142 patients (23.1%);
      independent predictors of their use overlapped with those of diuretics and
      moreover included treatment with loop diuretics (OR 3.52, 95% CI 2.66-4.66) and
      digoxin (OR 1.45, 95% CI 1.29-1.64). CONCLUSIONS: In this wide series of stable
      HF outpatients, cardiologists prescribed diuretics in accordance with published
      guidelines. Evolving prescription patterns of aldosterone-receptor blockers need
      to be further evaluated.

PMID- 12815572
TI  - Growth hormone resistance in chronic heart failure and its therapeutic
      implications.
AB  - BACKGROUND: In recent years the administration of recombinant human growth
      hormone (GH) has received great attention. This review compares the potential of
      this therapeutic intervention in heart failure with that in other diseases where
      wasting is commonly seen. The pathophysiologic importance of GH and insulin-like
      growth factor (IGF)-I in these conditions will be discussed. METHODS AND RESULTS:
      Abnormalities of the GH-IGF-I axis play an important role in the development of
      cachexia in chronic illnesses. GH resistance is a major determinant of the
      wasting process, acting through several different mechanisms: increased
      catabolism, impaired anabolism, and enhanced apoptosis in peripheral tissues. GH
      therapy has been evaluated in chronic heart failure (CHF); acquired GH resistance
      may explain the general lack of therapeutic success in the majority of studies.
      The assessment of plasma levels of GH, IGF-I, and, in particular, GH binding
      protein may help to guide dosing of GH for CHF patients. CONCLUSIONS: GH
      resistance might be overcome by use of intermittent or higher doses of GH, or
      alternatively by combining GH with IGF-I. Randomized studies of GH therapy in
      catabolic states, with targeted dosing and longer duration of treatment are
      required to fully assess the safety and efficacy of this treatment approach.

PMID- 12815573
TI  - Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume
      overloaded patients.
AB  - BACKGROUND: Veno-venous ultrafiltration may benefit patients with acute or
      chronic circulatory volume overload. Use of conventional systems, however, may be
      cumbersome, requiring physician placement of a double-lumen central venous
      catheter and use of a dedicated dialysis technician and apparatus. METHODS: A
      simplified peripheral ultrafiltration system including a miniaturized disposable
      circuit was evaluated in patients with volume-overload states. Separate
      intravenous catheters (16-18 G) for withdrawal and return of blood (blood flow
      <or= 40 mL/min, ultrafiltrate <or= 500 mL/h) were placed by nonphysician
      personnel in upper extremity veins. Twenty-five treatments of up to 8 hours were
      performed in 21 patients. RESULTS: The primary endpoint of greater than 1 L fluid
      removal in less than 8 hours was achieved in 23 of 25 treatments. On average,
      2611 +/- 1002 mL (maximum 3,725 mL) of ultrafiltrate was removed per treatment
      (treatment period 6:43 +/- 1:47 hours:minutes). Patient weight decreased from
      91.9 +/- 17.5 to 89.3 +/- 17.3 kg (P <.0001) after ultrafiltration. No major
      adverse events occurred. CONCLUSIONS: Rapid removal of extracellular and
      intravascular fluid volume excess can be safely achieved via peripherally
      inserted ultrafiltration without the need for central venous catheter placement.

PMID- 12815574
TI  - Endothelins and myocardial fibrosis.
AB  - BACKGROUND: Endothelins are associated with cardiac remodeling. These peptides
      are the most powerful vasoconstrictor described-whether this remodeling is a
      direct effect of this hormone or indirect response to a relative ischemia
      promoted by vasoconstrictor effect. We evaluated the role of endothelin upon
      myocardial fibrosis despite of its hemodynamic effects and the benefits of its
      antagonism. METHODS AND RESULTS: We used 40 Wistar rats: control, sham operated,
      rats had undergone myocardial infarction (MI) and MI rats treated with SB209670
      which is an ET(A)/ET(B) endothelin antagonist. We evaluated tail systolic blood
      pressure (BP) and left ventricular end diastolic pressure (LVED) before surgery,
      just after, and at the end of the study. Remodeling was studied based on
      interstitial collagen and MI size by an image system analysis. BP decreased in MI
      groups after surgery, but did not differ between treated and untreated animals.
      LVED had increased levels in MI groups after surgery and did not differ between
      them. However, ICVF had an increase in MI group but significantly less in
      MI+SB209670. MI size was similar in both groups. CONCLUSIONS: Endothelin may have
      a pivotal role in the myocardial fibrosis by direct stimulation of collagen
      accumulation despite of its hemodynamic effects.

PMID- 12815575
TI  - Adding angiotensin II type 1 receptor blockade to angiotensin-converting enzyme
      inhibition limits myocyte remodeling after myocardial infarction.
AB  - BACKGROUND: Adding angiotensin II type 1 receptor blockade (ARB) to angiotensin
      converting enzyme inhibition (ACEI) further attenuates left ventricular (LV)
      remodeling in an ovine model of myocardial infarction (MI). We hypothesized that
      combined therapy with ACEI and ARB (CT) would be additive in the limitation of
      the myocyte hypertrophy and dysfunction that occurs in untreated adjacent
      noninfarcted regions during remodeling. METHODS AND RESULTS: Nineteen sheep
      underwent coronary ligation to create a moderate-sized anteroapical infarction.
      Post-MI day 2, sheep were randomized to therapy with ramipril (ACEI, n = 5) or
      ramipril plus losartan (CT, n = 6) or none (untreated, n = 8). Infarct size was
      similar between groups. At 8 weeks post-MI, myocytes were isolated from regions
      adjacent to and remote from the infarct to measure morphometric indices (cell
      volume, length, cross-sectional area, width) and parameters of contraction (%
      shortening and -dL/dt, rate of shortening) and relaxation (+dL/dt [rate of
      relengthening] and TR 70% [time for 70% relengthening]). Volume % collagen was
      measured from adjacent and remote regions. Adjacent myocyte volume was different
      between groups (2.5 +/- 0.1 x 10(4) microm(3) in CT, 3.0 +/- 0.4 x 10(4)
      microm(3) in ACEI, 3.5 +/- 0.2 x 10(4) microm(3) in untreated, analysis of
      variance [ANOVA] P =.001) as was length (158 +/- 4 microm, 161 +/- 9 microm, 189
      +/- 8 microm, respectively, ANOVA P <.001). Adjacent cell volume and length in CT
      were lower than untreated (P <.05). Percent shortening and -dL/dt of isolated
      adjacent myocytes were improved with both ACEI (7.9 +/- 0.3%, -131 +/- 6
      microm/sec, P <.05) and CT (7.7 +/- 0.3%, -144 +/- 8 microm/sec, P <.05) compared
      with no therapy (6.4 +/- 0.4%, -104 +/- 7 microm/sec), as was both +dL/dt and TR
      70%. No between-group difference in volume % collagen was found in adjacent or
      remote regions. CONCLUSION: Compared with ACEI alone, the addition of ARB further
      limits adjacent noninfarcted myocyte hypertrophy during post-MI LV remodeling.
      Both ACEI alone and CT preserve isolated unloaded myocyte function, but neither
      significantly reduce interstitial collagen. The additional benefit of ARB on
      regional and global function in vivo may also be due to other factors including
      regional load.

PMID- 12815577
TI  - No regrets....

PMID- 12815578
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 1:
      Hallux valgus.

PMID- 12815579
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 2:
      Hallux rigidus.

PMID- 12815580
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 3:
      Hallux varus.

PMID- 12815581
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 4:
      Sesamoid disorders.

PMID- 12815582
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 5:
      Traumatic disorders.

PMID- 12815583
TI  - Diagnosis and treatment of first metatarsophalangeal joint disorders. Section 6:
      Other disorders.

PMID- 12815584
TI  - A comparison between the Regnauld arthroplasty and osteotomies of the first ray
      for the treatment of hallux valgus.
AB  - This article is a retrospective study comparing the efficacy of Regnauld
      arthroplasty to first ray osteotomies for the treatment of hallux valgus. One
      hundred consecutive cases of Regnauld arthroplasties were compared with 100
      consecutive first ray osteotomies. One hundred fourty-one patients were available
      for follow-up, and based on clinical/radiographic examinations, 72 were treated
      with the osteotomy protocol (group A) and 69 with Regnauld arthroplasty (group
      B). Age at surgery, clinical symptoms, and preoperative radiologic findings were
      similar for the 2 groups; there was a preponderance of female patients (90%). The
      average follow-up was 49 months in group A and 51 months in group B. Clinical
      evaluation showed in the osteotomy group a more stable correction (79% v 49%),
      greater pain reduction (measured in a visual analog scale from 0 = pain free to
      10 = deep intolerable pain), increased residual articular excursion of the first
      metatarsophalangeal joint (27 degrees of active dorsiflexion from neutral
      position v 8 degrees ), and less presence of central metatarsalgia (15% v 34%) (P
      <.05). The radiographic evaluation expressed more stable correction values in
      group A for the following parameters: joint preservation, sesamoid position,
      intermetatarsal angle (7 degrees v 12 degrees ), abduction angle of the hallux
      (14 degrees v 20 degrees ), and proximal articular set angle (8 degrees v 18
      degrees ) (P <.05).

PMID- 12815585
TI  - The effect of screw type on the biomechanical properties of SCARF and crescentic
      osteotomies of the first metatarsal.
AB  - The basilar crescentic osteotomy is a popular method for correcting moderate to
      severe hallux valgus. However, inadvertent dorsiflexion of the osteotomy can
      result from intraoperative malposition or from malunion after fixation failure.
      The mechanical properties of osteotomies are dependent on the nature of the
      osteotomy and the type of fixation. This study examines the mechanical properties
      of the SCARF and crescentic osteotomies of the first metatarsal by using a
      cannulated asymmetric pitched screw or AO cancellous screws. Sixteen human
      cadaveric first metatarsal specimens were tested in plantar to dorsiflexion
      cantilever bending by using a mechanical testing machine. The data was compared
      with our recent work on the mechanical properties of the SCARF and crescentic
      osteotomies. Ultimate load and stiffness of the SCARF osteotomy were superior to
      the crescentic osteotomy but were not dependent on screw type. Screw type was a
      prominent factor in the stiffness but not in the strength of the crescentic
      osteotomy. The ultimate load and the stiffness of SCARF osteotomy fixed with the
      cannulated asymmetric pitched screws were not significantly different compared
      with AO screws (ultimate load, 124.6 N [SD = 56.8] v 105.3 N [SD = 57.0];
      stiffness, 52.0 N/mm [SD = 48.0] v 31.8 N/mm [SD = 19.0]). Modes of failure were
      fracture of the cortical bone bridge between the screw hole and the osteotomy in
      all crescentic osteotomies and fracture of the proximal dorsal bridge in all
      SCARF osteotomies. The superior mechanical properties of the SCARF osteotomy,
      fixed with cannulated asymmetric pitched screws, make this a more secure
      construct, with less risk of malunion than the crescentic osteotomy. Stiffness is
      an important mechanical factor that helps distinguish the mechanical performance
      of different osteotomy techniques.

PMID- 12815586
TI  - Hallux valgus surgery: a simple method for evaluating the first-second
      intermetatarsal angle in the presence of metatarsus adductus.
AB  - In hallux valgus surgery, the presence of metatarsus adductus complicates the
      evaluation of the first-second intermetatarsal angle(IMA) because it will produce
      an apparent reduction in the IMA because the second metatarsal is skewed closer
      to the first metatarsal. This can lead to an underestimation of how much the IMA
      should be reduced. The Kilmartin angle is a simple charting technique that will
      eliminate the influence of metatarsus adductus and indicate the true degree of
      metatarsus primus varus. This may facilitate better preoperative planning in
      hallux valgus surgery.

PMID- 12815587
TI  - Use of the Z osteotomy for Tailor bunionectomy.
AB  - The authors present a unique use of the Z osteotomy in the fifth metatarsal for
      correction of Tailor bunion. The rotational capabilities of the Z osteotomy are
      exploited to provide correction of fifth metatarsal lateral bowing and to
      decrease intermetatarsal angles. The osteotomy is inherently stable, and the
      design facilitates internal fixation.

PMID- 12815588
TI  - One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome
      and autosomal dominant brachydactyly type B.
AB  - Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with
      short stature, generalized limb shortening, segmental defects of the spine,
      brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor
      orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and
      homozygous loss-of-function mutations in this gene are responsible for RRS.
      Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the
      homozygous state, with almost identical features to recessive Robinow syndrome.
      The protein product of this gene is a cell membrane receptor, containing distinct
      motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine
      rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region;
      and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and
      proline-rich structures. The extracellular motifs of the ROR2 protein are known
      to be involved in protein-protein interactions. The tyrosine kinase domain is
      involved in an as yet uncharacterized signaling pathway. Interestingly,
      heterozygous mutations in ROR2 have recently been shown to give rise to autosomal
      dominant brachydactyly type B1 (BDB1). This condition is characterized by
      terminal deficiency of fingers and toes. A variety of mutations have been
      reported in ROR2. Here, these genetic defects are compiled and possible genotype
      phenotype correlations are discussed.

PMID- 12815589
TI  - Clear relationship between ETF/ETFDH genotype and phenotype in patients with
      multiple acyl-CoA dehydrogenation deficiency.
AB  - Mutations in electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH)
      are the molecular basis of multiple acyl-CoA dehydrogenation deficiency (MADD),
      an autosomal recessively inherited and clinically heterogeneous disease that has
      been divided into three clinical forms: a neonatal-onset form with congenital
      anomalies (type I), a neonatal-onset form without congenital anomalies (type II),
      and a late-onset form (type III). To examine whether these different clinical
      forms could be explained by different ETF/ETFDH mutations that result in
      different levels of residual ETF/ETFDH enzyme activity, we have investigated the
      molecular genetic basis for disease development in nine patients representing the
      phenotypic spectrum of MADD. We report the genomic structures of the ETFA, ETFB,
      and ETFDH genes and the identification and characterization of seven novel and
      three previously reported disease-causing mutations. Our molecular genetic
      investigations of these nine patients are consistent with three clinical forms of
      MADD showing a clear relationship between the nature of the mutations and the
      severity of disease. Interestingly, our data suggest that homozygosity for two
      null mutations causes fetal development of congenital anomalies resulting in a
      type I disease phenotype. Even minute amounts of residual ETF/ETFDH activity seem
      to be sufficient to prevent embryonic development of congenital anomalies giving
      rise to type II disease. Overexpression studies of an ETFB-D128N missense
      mutation identified in a patient with type III disease showed that the residual
      activity of the mutant enzyme could be rescued up to 59% of that of wild-type
      activity when ETFB-D128N-transformed E. coli cells were grown at low temperature.
      This indicates that the effect of the ETF/ETFDH genotype in patients with milder
      forms of MADD, in whom residual enzyme activity allows modulation of the
      enzymatic phenotype, may be influenced by environmental factors like cellular
      temperature.

PMID- 12815590
TI  - Identification of 16 novel mutations in the argininosuccinate synthetase gene and
      genotype-phenotype correlation in 38 classical citrullinemia patients.
AB  - Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused
      by mutations of the argininosuccinate synthetase (ASS) gene, localized on
      chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle.
      Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly
      in Japan and the United States, and to date 34 different mutations have been
      described in 50 families worldwide. In the present study, we report ASS mutations
      detected in 35 additional CTLN1 families from 11 countries. By analyzing the
      entire coding sequence and the intron-exon boundaries of the ASS gene using RT
      PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different
      1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known
      mutations. Altogether, 50 different mutations (seven deletion, three splice site,
      one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were
      identified. On the basis of primary sequence comparisons with the crystal
      structure of E. coli ASS protein, it may be concluded that any of the 37 missense
      mutations found at 30 different positions led to structural and functional
      impairments of the human ASS protein. It has been found that three mutations are
      particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three),
      G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one,
      Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan:
      nine and Turkey: one). Most mutations of the ASS gene are "private" and are
      distributed throughout the gene, except for exons 5 and 12-14. It seems that the
      clinical course of the patients with truncated mutations or the G390R mutation is
      early-onset/severe. The phenotype of the patients with certain missense mutations
      (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H,
      or K310R mutations were adult/late-onset and four of them showed severe symptoms
      during pregnancy or postpartum. However, it is still difficult to prove the
      genotype-phenotype correlation, because many patients were compound heterozygotes
      (with two different mutations), lived in different environments at the time of
      diagnosis, and/or had several treatment regimes or various knowledge of the
      disease.

PMID- 12815591
TI  - Spectrum of CLN6 mutations in variant late infantile neuronal ceroid
      lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive
      neurodegenerative diseases of childhood. CLN6, the gene mutated in variant late
      infantile NCL (vLINCL), was recently cloned. We report the identification of
      eight further mutations in CLN6 making a total of 18 reported mutations. These
      mutations include missense, nonsense, small deletions or insertions, and two
      splice-site mutations. Ten mutations affect single amino acids, all of which are
      conserved across vertebrate species. Minor differences in the pattern of disease
      symptom evolution can be identified. One patient with a more protracted disease
      progression was a compound heterozygote for a missense mutation and an
      unidentified mutation. Fifteen CLN6 mutations occur in one or two families only,
      and families from the same country do not all share the same mutation. Unlike
      NCLs caused by mutations in CLN1, CLN3, CLN5, and CLN8, there is no major founder
      mutation in CLN6. However, one mutation (E72X) is significantly more common in
      patients from Costa Rica than two other mutations present in that same
      population. In addition, a 1-bp insertion (c.316insC) is associated with families
      from Pakistan and I154del may be common in Portugal. A group of Roma Gypsy
      families from the Czech Republic share two disease-associated haplotypes, one of
      which is also present in a Pakistani family, consistent with the proposed
      migration of the Roma from the Indian subcontinent 1,000 years ago. All mutations
      are recorded in the NCL Mutation Database together with their country of origin
      for use in the development of rapid screening assays to confirm diagnosis and to
      facilitate carrier testing appropriate to a population.

PMID- 12815593
TI  - A phylogenetic approach to assessing the significance of missense mutations in
      disease genes.
AB  - The identification of deleterious mutations within candidate genes is a crucial
      step in the elucidation of the genetic bases of human disease. However, the
      significance of any base or amino acid change within a gene is unknown until
      detailed structural and functional analysis has been carried out. A potentially
      rapid way of identifying functionally important sites within a gene is to
      identify evolutionarily conserved regions. Mutations affecting such sites are
      assumed to be deleterious for the carrier. In this communication we generalize
      this approach and present a formal framework to assess whether a specific
      mutation is deleterious given sequence data from a set of homologues. We propose
      a score that takes into account the nature of the mutation, the conservation of
      the affected residue among the different species, and their phylogenetic
      relationships. Its performance is examined using published TP53 mutations and
      frequent polymorphic variants.

PMID- 12815592
TI  - Independent mutational events are rare in the ATM gene: haplotype prescreening
      enhances mutation detection rate.
AB  - Mutations in the ATM gene are responsible for the autosomal recessive disorder
      ataxia-telangiectasia (A-T). Many different mutations have been identified using
      various techniques, with detection efficiencies ranging from 57 to 85%. In this
      study, we employed short tandem repeat (STR) haplotypes to enhance mutation
      identification in 55 unrelated A-T families of Iberian origin (20 Spanish, 17
      Brazilian, and 18 Hispanic-American); we were able to identify 95% of the
      expected mutations. Allelic sizes were standardized based on a reference sample
      (CEPH 1347-2). Subsequent mutation screening was performed by PTT, SSCP, and
      DHPLC, and abnormal regions were sequenced. Many STR haplotypes were found within
      each population and six haplotypes were observed across several of these
      populations. Single nucleotide polymorphism (SNP) haplotypes further suggested
      that most of these common mutations are ancestrally related, and not hot spots.
      However, two mutations (8977C>T and 8264_8268delATAAG) may indeed be recurring
      mutational events. Common haplotypes were present in 13 of 20 Spanish A-T
      families (65%), in 11 of 17 Brazilian A-T families (65%), and, in contrast, in
      only eight of 18 Hispanic-American families (44%). Three mutations were
      identified that would be missed by conventional screening strategies. In all, 62
      different mutations (28 not previously reported) were identified and their
      associated haplotypes defined, thereby establishing a new database for Iberian A
      T families, and extending the spectrum of worldwide ATM mutations.

PMID- 12815594
TI  - Genetic diversity of the alpha-1-antitrypsin gene in Africans identified using a
      novel genotyping assay.
AB  - The highly polymorphic human alpha-1-antitrypsin (AAT) gene, more recently named
      SERPINA1, codes for the most abundant circulating plasma serine protease
      inhibitor, protease inhibitor 1 (PI). Most studies determining AAT haplotype
      frequencies have been restricted first by the limited accuracy of the phenotypic
      method used and secondly by the analysis of predominantly Caucasian populations.
      Limited studies have been performed on African-based populations. Here a new
      comprehensive assay for genotyping the entire coding region, including splice
      junctions, of the AAT gene was designed. This assay, based on denaturing gradient
      gel electrophoresis (DGGE), allows for the complete analysis of a single
      individual in two lanes on a gel. Application of the assay resulted in the
      identification of nine known AAT variants as well as 13 novel sequence variants,
      five of which are single nucleotide polymorphisms (SNPs), occurring exclusively
      in the African-based populations. This is the first comprehensive analysis of the
      genetic diversity of the AAT gene in a cohort from sub-Saharan Africa.

PMID- 12815595
TI  - The molecular basis of glutamate formiminotransferase deficiency.
AB  - Glutamate formiminotransferase deficiency, an autosomal recessive disorder and
      the second most common inborn error of folate metabolism, is presumed to be due
      to defects in the bifunctional enzyme glutamate formiminotransferase
      cyclodeaminase (FTCD). Features of a severe phenotype, first identified in
      patients of Japanese descent, include elevated levels of formiminoglutamate
      (FIGLU) in the urine in response to histidine administration, megaloblastic
      anemia, and mental retardation. Features of a mild phenotype include high urinary
      excretion of FIGLU in the absence of histidine administration, mild developmental
      delay, and no hematological abnormalities. We found mutations in the human FTCD
      gene in three patients with putative glutamate formiminotransferase deficiency.
      Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and
      c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed
      that the R135C mutation reduced formiminotransferase activity to 61% of wild
      type, whereas the R299P mutation reduced this activity to 57% of wild-type. The
      third patient was hemizygous for c.1033insG, with quantitative PCR indicating
      that the other allele contained a deletion. These mutations are the first
      identified in glutamate formiminotransferase deficiency and demonstrate that
      mutations in FTCD represent the molecular basis for the mild phenotype of this
      disease.

PMID- 12815596
TI  - Determination of SMN1 and SMN2 copy number using TaqMan technology.
AB  - Infantile spinal muscular atrophy (SMA) is a neuromuscular disease caused by
      homozygous deletion of the SMN1 gene in more than 90% of patients. Identification
      of carriers for the SMN1 deletion is important for diagnostic purposes and for
      genetic counseling. The current practical implications of SMN2 copy number
      determination are limited but may be important, for example, for future drug
      trials. Here we present a new rapid and reliable approach to determine the copy
      numbers of the SMN1 and SMN2 genes: For differentiation of the two genes, we
      developed a quantitative test on the basis of TaqMan technology using minor
      groove binder (MGB) probes. To evaluate the approach in respect to detection of
      SMN1 deletion carriers, we tested 40 putative carriers as well as 100 controls.
      We confirmed the carrier status in all individuals; furthermore, the distribution
      of SMN1 and SMN2 copies in the control cohort corresponded to that published
      previously. In total, a clear-cut differentiation between the different copy
      number ranges could be observed for both genes. This distinct differentiation is
      based on the exact specificity of MGB probes and the parallel analysis of an
      external reference locus that circumvents the problem of unavoidable deviations
      in DNA concentrations. The simplicity and reproducibility of the TaqMan assay
      presented here should facilitate its establishment in molecular diagnostic
      laboratories. Nevertheless, the applicability of quantitative analyses of SMN
      copy numbers requires knowledge about its options and limitations, based on the
      complex nature of the SMN region and the clinical variability of SMA. Therefore,
      determination of SMN1 and SMN2 copy numbers should only be offered after careful
      consideration in each case.

PMID- 12815597
TI  - Enhanced allele-specific PCR discrimination in SNP genotyping using 3' locked
      nucleic acid (LNA) primers.
AB  - The specificity and reliability of locked nucleic acid (LNA) substitution at the
      3' position of allele-specific PCR (AS-PCR) primers for SNP detection was
      investigated in direct comparison to DNA primers. Both plasmid and human genomic
      DNA templates were examined in this study. All possible DNA and 3' LNA mismatch
      combinations were tested in triplicate with the plasmid target. LNA primers yield
      consistently low amounts of mismatch products with all base combinations, whereas
      certain mismatches with DNA primers generate strong false positive amplicons.
      Amplified human SNP alleles within the cystic fibrosis (CFTR) gene were analyzed
      in AS-PCR by gel analysis and real-time fluorescence generation. A 3' LNA residue
      in the primer at the SNP site improves allelic discrimination and functions under
      a wide window of PCR conditions. We demonstrate increased AS-PCR specificity with
      comparable sensitivity using 3' LNA primers in gel electrophoresis and real-time
      detection experiments. This increase in AS-PCR discrimination with 3' LNA primers
      should facilitate the use of this simple, rapid, and inexpensive technique for
      SNP genotyping applications.

PMID- 12815598
TI  - A specific GFP expression assay, penetrance estimate, and histological assessment
      for a putative splice site mutation in BRCA1.
AB  - Genetic testing for cancer predisposing mutations in BRCA1 and BRCA2 has been of
      benefit to many individuals from breast and ovarian cancer-prone kindreds.
      However, a function has not been assigned to many of the domains that make up
      these complex proteins and hence, the significance of many sequence variants,
      including missense mutations, splice-site mutations, and in-frame
      deletions/insertions, remains unclear. We identified a putative splice site
      mutation (IVS6-2delA) in BRCA1 in a family attending a Familial Cancer Centre
      that had a significant history of both breast and ovarian cancer. This sequence
      variant was not novel but the exact effect on mRNA splicing and hence the
      biological impact of this sequence variation was unclear and therefore the
      finding was unable to be used in genetic counseling of the family. Via the
      construction of novel GFP-based expression fusion constructs, we demonstrated
      that this sequence variation prevented normal splicing of the BRCA1 transcript.
      By combining these data with an assessment of the histopathological features of
      the breast carcinomas in this family and mutation penetrance estimate we were
      able to conclude that this BRCA1 variant conveyed an increased risk of breast
      cancer.

PMID- 12815599
TI  - Epigenetic detection of human chromosome 14 uniparental disomy.
AB  - The recent demonstration of genomic imprinting of DLK1 and MEG3 on human
      chromosome 14q32 indicates that these genes might contribute to the discordant
      phenotypes associated with uniparental disomy (UPD) of chromosome 14. Regulation
      of imprinted expression of DLK1 and MEG3 involves a differentially methylated
      region (DMR) that encompasses the MEG3 promoter. We exploited the normal
      differential methylation of the DLK1/MEG3 region to develop a rapid diagnostic
      PCR assay based upon an individual's epigenetic profile. We used methylation
      specific multiplex PCR in a retrospective analysis to amplify divergent lengths
      of the methylated and unmethylated MEG3 DMR in a single reaction and accurately
      identified normal, maternal UPD14, and paternal UPD14 in bisulfite converted DNA
      samples. This approach, which is based solely on differential epigenetic
      profiles, may be generally applicable for rapidly and economically screening for
      other imprinting defects associated with uniparental disomy, determining loss of
      heterozygosity of imprinted tumor suppressor genes, and identifying gene-specific
      hypermethylation events associated with neoplastic progression.

PMID- 12815600
TI  - Denaturing HPLC analysis of DNA deletions and insertions.
AB  - Denaturing HPLC (DHPLC) is a useful technique for the fast screening of known and
      unknown heterozygous gene mutations. Most DNA mutations causing genetic disorders
      consist of nucleotide substitutions, but insertions and deletions occur, albeit
      less frequently. The heteroduplexes with insertions/deletions have gaps that may
      affect molecular stability differently from the mismatches caused by
      substitutions. Therefore, gaps and mismatches may be distinguished by DHPLC
      analysis, which is based on the differential thermal stability of amplicons with
      different characteristics. To verify this hypothesis, we examined 12 DNA samples
      containing insertions and deletions of different sizes (one to 29 residues) from
      four different genes (ABCA4, CFTR, FTL, and SLC11A3). We found that all of them
      were detected by DHPLC runs at 50 degrees C, which is considered a non-denaturing
      temperature, as well as by runs at the temperature optimized for mismatch
      recognition. The finding confirms that gaps reduce heteroduplex stability more
      than mismatches, and indicates that DHPLC analysis at low temperature may be
      applied to distinguish DNA deletions/insertions from substitutions.

PMID- 12815601
TI  - Screening for large rearrangements of the BRCA1 gene in German breast or ovarian
      cancer families using semi-quantitative multiplex PCR method.
AB  - Since the identification of the breast and ovarian cancer susceptibility genes
      BRCA1 and BRCA2, a large number of different germline mutations in both genes
      have been found by conventional PCR-based mutation detection methods. Complex
      germline rearrangements such as those reported in the BRCA1 gene are often not
      detectable by these standard diagnostic techniques. To detect large deletions or
      duplications encompassing one or more exons of the BRCA1 gene and in order to
      estimate the frequency of BRCA1 rearrangements in German breast or ovarian cancer
      families, a semi-quantitative multiplex PCR method was developed and applied to
      DNA samples of patients from families negatively tested for disease causing
      mutations in the BRCA1 and BRCA2 coding regions by direct sequencing. Out of 59
      families analysed, one family was found to carry a rearrangement in the BRCA1
      gene (duplication of exon 13). The results indicate that the semi-quantitative
      multiplex PCR method is useful for the detection of large rearrangements in the
      BRCA1 gene and therefore represents an additional valuable tool for mutation
      analysis of BRCA1 and BRCA2.

PMID- 12815602
TI  - Spectrum of CBS mutations in 16 homocystinuric patients from the Iberian
      Peninsula: high prevalence of T191M and absence of I278T or G307S.
AB  - Homocystinuria due to cystathionine beta-synthase (CBS) deficiency has been
      extensively studied, but to date, no spectrum of CBS mutations of Spanish
      homocystinuric patients has been reported. Here we present a mutation analysis of
      thirteen Spanish and three Portuguese unrelated homocystinuric patients. Ten
      mutations were found to account for the thirty-two mutant alleles and five of
      these (C275Y, L338P, S349N, R379Q, and L456P) are reported here for the first
      time. All five novel mutations were found to affect evolutionarily conserved
      residues suggesting that they may impair enzyme function. Interestingly, neither
      of the two common CBS mutations, I278T and G307S, was detected in this series,
      and no patient was found to respond to pyrodoxine. Enzyme activities in cultured
      fibroblasts from 10 of the patients were assayed, and they ranged from 0 to 13 %
      of controls analyzed in parallel. The T191M mutation (which has only ever been
      reported once before in a Spanish patient) accounted for 50% of the mutant
      alleles. Comparison of the clinical data of seven patients homozygous for T191M
      indicated that this genotype is a poor predictor of the phenotype. A common
      haplotype was identified in all the T191M chromosomes of Spanish origin, while a
      different one was present in the four T191M chromosomes from Portuguese patients.

PMID- 12815603
TI  - Prion susceptibility and protective alleles exhibit marked geographic
      differences.
AB  - A total of 616 chromosomes from control individuals of all major continental
      groups, and six individuals affected by either Creutzfeldt-Jakob disease (CJD) or
      fatal familial insomnia (FFI), were typed with a new single-reaction protocol
      method and were also sequenced, with total reproducibility to screen variation at
      important positions (385A>G: M129V and 655G>A: E219K) in the human prion protein
      gene (PRNP). We have found, for the first time, that 129V allele is highly
      represented in some populations from the Americas, and that 129M and 129V are in
      similar frequencies in Africa. The 129M susceptibility allele was found at high
      frequencies in Old World populations, very high in the Pacific ( approximately
      81%) and up to 93% in Central and East Asia, but at a low frequency
      (approximately 30%) in Native Americans. The protective 219L allele was
      restricted to Asian and Pacific populations. Susceptibility alleles exhibit
      marked geographic differences in frequency, and thus, differences in probability
      to develop prion diseases.

PMID- 12815604
TI  - The analysis of BRCA1 mutations in eastern Chinese patients with early onset
      breast cancer and affected relatives.
AB  - To study the BRCA1 mutations in eastern Chinese patients with early onset breast
      cancer and affected relatives, 41 patients' genomic DNA from peripheral
      mononuclear blood cells was studied by using single strand conformational
      polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the
      whole gene sequence. Three novel disease-causing mutations (c.582C>T, c.735C>T
      and c.2790delT) occurred in all the patients. Two occurred in the patients
      younger than 35 years old (9.1%) and one in the patients with affected relatives
      (5%). Additional sequence variants identified included a novel missense mutation
      of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations
      in Chinese patients in Shanghai with early onset breast cancer is similar to that
      observed in western women, but the incidence of mutations in breast cancer
      patients in Shanghai with affected relatives isn't as high as that in western
      women.

PMID- 12815605
TI  - Six novel mutations of the RUNX2 gene in Italian patients with cleidocranial
      dysplasia.
AB  - We report clinical and molecular findings in 14 patients with cleidocranial
      dysplasia (CCD), a well defined skeletal disorder with characteristic clinical
      findings and autosomal dominant inheritance. We identified ten heterozygous base
      changes in the RUNX2 gene, including six novel mutations [c.522insA, c.389G>A
      (W130X), c.662T>G (V221G), IVS2+T>A, c.1111_1129del19, and c.873_874delCA]. We
      did not establish a clear correlation between clinical features and genotype, the
      phenotypes of all patients analyzed falling within the range of variation
      described in CCD without an effect related to the length of the predicted
      protein. In two cases, however, a limb-girdle myopathy affecting the shoulder
      muscles was also identified. Our data add new variants to the repertoire of RUNX2
      mutations in CCD.

PMID- 12815606
TI  - Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL
      gene.
AB  - Hypophosphatasia is an inherited disorder characterized by defective bone
      mineralization and deficiency of serum and tissue liver/bone/kidney alkaline
      phosphatase (L/B/K ALP) activity. We report the characterization of ALPL gene
      mutations in a series of 11 families from various origins affected by perinatal
      and infantile hypophosphatasia. Sixteen distinct mutations were found, fifteen of
      them not previously reported: M45V, G46R, 388-391delGTAA, 389delT, T131I, G145S,
      D172E, 662delG, G203A, R255L, 876-881delAGGGGA, 962delG, E294K, E435K, and A451T.
      This confirms that severe hypophosphatasia is due to a large spectrum of
      mutations in Caucasian populations.

PMID- 12815607
TI  - Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic
      origin from Brittany (France) and Ireland.
AB  - This study aims to compare the spectrum of the mutations identified in the gene
      responsible for cystic fibrosis in three cohorts of patients of Celtic origin
      from Brittany and Ireland. It included 389 patients from Brittany, 631 from
      Dublin and 139 from Cork. The CFTR gene analysis relied on the detection of the
      most common mutations, followed by a complete gene scanning using DGGE or D-HPLC.
      High mutation detection rates were obtained in each cohort: 99.6%, 96.8%, and
      96.0% respectively. A high frequency of the c.1652_1655 del3 mutation (F508del:
      74.8% to 81.3%) and of the "Celtic" mutation (c.1784G>A (G551D): 3.7% to 9.7%)
      was observed in each population. Apart from this, the mutation spectrums
      differed. In Brittany, the most common abnormalities were: c.1078delT (3.6%),
      c.4041C>G (N1303K: 1.4%), c.2670G>A (W846X(2): 1.0%) and c.1717-1G>A (1.0%),
      whereas in the cohort of Dublin, the main mutations were: c.482G>A (R117H: 3.0%),
      c.1811G>C (R560T: 2.4%) and c.621+1G>T (1.7%). Finally, in the Cork area, only
      the c.482G>A mutation (R117H) reached a frequency of 1%. Two previously
      unreported mutations were identified in the Dublin cohort: c.2623-2A>G and
      c.3446T>G (M1105R). This collaborative study highlights the similarities of the
      CFTR alleles in the Breton and Irish populations, but also the disparities that
      exist between these populations, despite their common origin. Each population has
      its own history, with its mixture of founder effects and genetic drifts, which
      are at the origin of the current mutation distribution. The molecular study of
      the CFTR gene provides new tools for retracing European populations' histories.

PMID- 12815608
TI  - Gene expression in rat skin induced by irritating chemicals.
AB  - Occupational skin disease is the second most significant cause of occupational
      disease, after accidents. Irritation from occupational chemicals such as
      solvents, hydrocarbons, and surfactants are one cause of this disease. Gene
      expression studies provide useful information about normal processes in the skin
      and responses of the skin to exogenous chemicals. We exposed rats, cutaneously,
      to sodium lauryl sulfate (SLS, 1% and 10% aqueous solution), m-xylene (pure
      liquid), and d-limonene (pure liquid) for 1 h and measured transcriptional
      responses at the end of the exposure and 3 h later for comparison with untreated
      skin samples. Total skin RNA was isolated and analyzed using the Affymetrix
      RatTox U34 array. Using the Affymetrix software, we found that 234 of
      approximately 850 genes were detected as present in at least 80% of the normal
      skin samples. The largest number of these genes was related to metabolism,
      oxidative/cellular stress, and signal transduction. Limonene caused the largest
      change in mRNA levels with a total of 34 increased transcripts and 4 decreased
      transcripts. Xylene treatment resulted in 6 increased transcripts and 14
      decreased transcripts, while 10% SLS caused 5 transcripts to increase and 17 to
      decrease. Only two transcripts were observed to change in skin following a 1% SLS
      exposure. Sodium lauryl sulfate transcript changes increased with dose and were
      maximum at 4 h. Limonene transcript changes were more numerous at 1 h than at 4
      h. The observed differences may reflect different mechanisms of irritation.

PMID- 12815609
TI  - Changes in expression and activity of glutathione S-transferase in different
      organs of schistosoma haematobium-infected hamster.
AB  - Schistosomiasis is a major health problem in many subtropical developing
      countries, causing a number of serious pathologies, including bladder cancer.
      Most of the toxic compounds formed as a result of these infestations are derived
      either exogenously or formed endogenously and can be conjugated with glutathione
      (GSH) via glutathione S-transferase (GST). The present study investigates the
      effect of Schistosma haematobium infection on the activity of GST and glutathione
      reductase (GR) and levels of glutathione and free radicals (measured as
      thiobarbituric acid reactive substances) in different organs of the male hamster.
      The total activity of GST was increased in several organs; in kidney by 50 and
      46% at 6 and 10 weeks postinfection, respectively, and in bladder tissues by 169,
      23, and 130% at 2, 4, and 6 weeks postinfection, respectively. In support of
      this, the expression of GST isozymes was also induced in kidney and bladder
      tissues at early stages (2, 4, and 6 weeks) and reduced at the later stages of
      infection (8 and 10 weeks). In contrast, the expression of these isozymes was
      decreased in the spleen and liver at 2, 4, 6, 8, and 10 weeks postinfection.
      Also, such activity was decreased in lungs by 74 and 78% and in bladders by 65
      and 72% at 8 and 10 weeks postinfection, respectively. GSH levels increased in
      lungs by 95, 40, and 56% at 2, 4, and 6 weeks and in spleen by 26 and 74% at 4
      and 6 weeks, respectively, but decreased at later stages of S. haematobium
      infection in these organs. The depletion of GSH levels also occurred in bladders
      by 72 and 54% at 8 and 10 weeks postinfection, respectively. The activity of GR
      was increased in the livers, lungs, and kidneys of the S. haematobium-infected
      hamster. TBARS also increased in the lung by 14, 65, 53, 828, and 624% and in the
      kidney by 64, 29, 87, 190, and 111%, and in the bladder by 216, 23, 1468, 528,
      and 1025% at 2, 4, 6, 8, and 10 weeks postinfection, respectively. This study
      indicates that low GST expression and high levels of free radicals could provide
      new evidence for damage to the bladder and other organs as a result of S.
      haematobium infection.

PMID- 12815610
TI  - Effect of oral administration of Arabic gum on cisplatin-induced nephrotoxicity
      in rats.
AB  - It has been recently postulated from our laboratory that Arabic gum (AG) offers a
      protective effect in the kidney of rats against nephrotoxicity induced by
      gentamicin via inhibiting lipid peroxidation. It has also recently shown a
      powerful antioxidant effect through scavenging superoxide anions. In this study
      we utilized a rat model of cisplatin (CP)-induced nephrotoxicity to determine its
      peak time following (1, 2, 5, and 7 days) of a single CP (7.5 mg/kg, i.p.)
      injection. Also, a possible protective effect of cotreatment with AG (7.5
      g/kg/day p.o.) on CP-induced nephrotoxicity was investigated. Biochemical as well
      as histological assessments were carried out. CP-induced nephrotoxicity was
      manifested by significant elevations of the functional parameters blood urea,
      serum creatinine, and kidney/body weight ratio. Maximum toxic effects of CP were
      observed 5 days after its injection, while it started after day 1 in the
      biochemical parameters, such as glutathione depletion in the kidney tissue with
      concomitant increases in lipid peroxides and platinum content. Additionally,
      severe necrosis and desquamation of tubular epithelial cells in renal cortex as
      well as interstitial nephritis were observed after 5 days in CP-treated animals.
      Five days after AG cotreatment with CP did not protect the kidney from the
      damaging effects of CP. However, it significantly reduced CP-induced lipid
      peroxidation. These findings suggest that lipid peroxidation is not the main
      cause of CP-induced nephrotoxicity but it is rather more dependent on other
      factors such as platinum disposition in renal interstitial tubules.

PMID- 12815611
TI  - Voltage-dependent ebselen and diorganochalcogenides inhibition of 45Ca2+ influx
      into brain synaptosomes.
AB  - By mediating the Ca(2+) influx, Ca(2+) channels play a central role in
      neurotransmission. Chemical agents that potentially interfere with Ca(2+)
      homeostasis are potential toxic agents. In the present investigation, changes in
      Ca(2+) influx into synaptosomes by organic forms of selenium and tellurium were
      examined under nondepolarizing and depolarizing conditions induced by high KCl
      concentration (135 mM) or by 4-aminopyridine (4-AP). Under nondepolarizing
      conditions, ebselen (400 micro M) increased Ca(2+) influx; diphenyl ditelluride
      (40-400 micro M) decreased Ca(2+) in all concentrations tested; and diphenyl
      diselenide decreased Ca(2+) influx at 40 and 100 micro M, but had no effect at
      400 micro M. In the presence of KCl as depolarizing agent, ebselen and diphenyl
      ditelluride decreased Ca(2+) influx in a linear fashion. In contrast, diphenyl
      diselenide did not modify Ca(2+) influx into isolated nerve terminals. In the
      presence of 4-AP (3 mM) as depolarizing agent, ebselen (400 micro M) caused a
      significant increase, whereas diphenyl diselenide and diphenyl ditelluride
      inhibited Ca(2+) influx into synaptosomes. The results can be explained by the
      fact that the mechanism through which 4-AP and high K(+) induced elevation of
      intracellular Ca(2+) is not exactly coincident. The mechanism by which diphenyl
      ditelluride and ebselen interact with Ca(2+) channel is unknown, but may be
      related to reactivity with critical sulfhydryl groups in the protein complex. The
      results of the present study indicate that the effects of organochalcogenides
      were rather complex depending on the condition and the depolarizing agent used.

PMID- 12815612
TI  - Relationship between expression of HSP70 and metallothionein and oxidative stress
      during mercury chloride induced acute liver injury in rats.
AB  - Mercury is a highly toxic metal which induces oxidative stress. Metallothionein
      and heat shock protein 70 (HSP70) are stress proteins involved in response to
      different stimuli. In the present study rats were administered per oral
      application by gavage, a single daily dose (0.1 mg/kg) of HgCl(2) for 3
      consecutive days. To find a relation between these two stress proteins and
      mercury, parameters of liver injury, redox state of the cells, and the expression
      and protein levels of HSP70 and metallothionein by Northern and Western blot
      analysis were assayed either in blood or in liver. HgCl(2) at the doses of 0.1
      mg/kg induced liver injury detected by a slight increase in serum aspartate
      aminotransferase and alkaline phosphatase activities and by the enhanced levels
      of bilirubin. Oxidative stress was detected by a significant decrease in protein
      SH and an increase in thiobarbituric acid reactive substances in liver following
      one dose of mercury. mRNA and protein levels of both metallothionein and HSP70
      increased progressively from first to third doses of mercury. We conclude that
      against low doses of mercury that produce a slight liver injury and oxidative
      stress, the liver rapidly responds by inducing the expression of metallothionein
      and HSP70. We suggest that metallothionein induction attenuates the decrease in
      protein-SH induced by the first dose of mercury, since metallothionein increases
      the pool of thiol groups in the cytosol eliminating oxygen radicals and
      inhibiting lipid peroxidation. From these results we can suggest that the changes
      observed in these stress proteins by the effect of mercury appear to be a
      response rapidly induced at transcriptional and at translational levels.

PMID- 12815613
TI  - Catalyzation of cocaine N-demethylation by cytochromes P4502B, P4503A, and P4502D
      in fish liver.
AB  - Cocaine N-demethylation by microsomal cytochrome P450s is the principal pathway
      in cocaine bioactivation and hepatotoxicity. P450 isozymes involved in N
      demethylation of cocaine have not been elucidated yet and they differ from
      species to species. In humans and mice, P4503A contributes to cocaine N
      demethylase activity, whereas in rats, both P4503A and P4502B participate. In the
      present study, contribution of different P450 isozymes to cocaine N-demethylase
      activity was studied in vitro with fish liver microsomes. The specific cocaine N
      demethylase activity was found to be 0.672 +/- 0.22 nmol formaldehyde
      formed/min/mg protein (mean +/- SD, n = 6). Cocaine N-demethylase exhibited
      biphasic kinetics, and from the Lineweaver-Burk plot, two K(m) values were
      calculated as 0.085 and 0.205 mM for the high- and low-affinity enzyme. These
      results indicate that N-demethylation of cocaine in mullet liver microsomes is
      catalyzed by at least two cytochrome P450 isozymes. Inhibitory effects of
      cytochrome P450 isozyme-selective chemical inhibitors, ketoconazole, cimetidine,
      SKF-525A, and quinidine, on cocaine N-demethylase activity were studied at 50,
      100, and 500 micro M concentrations of these inhibitors. At 100 micro M final
      concentrations, ketoconazole (P4503A inhibitor), SKF-525A (inhibitor of both
      P4502B and P4503A), and cimetidine (P4503A inhibitor) inhibited N-demethylation
      activity by 73, 69, and 63%, respectively. Quinidine, P4502D-specific inhibitor,
      at 100 micro M final concentration, reduced N-demethylation activity down to 64%.
      Aniline, a model substrate for P4502E1, did not alter N-demethylase activity in
      the final concentration of 100 micro M. IC(50) values were calculated to be 20
      micro M for ketoconazole, 48 micro M for cimetidine (both specific P4503A
      inhibitors), 164 micro M for quinidine (P4502D inhibitor), and 59 micro M for SKF
      525A (inhibitor of both P4503A and P4502B). The contribution of P4502B to cocaine
      N-demethylase activity in mullet liver microsomes was further explored by the use
      of purified mullet cytochrome P4502B in the reconstituted system containing
      purified mullet P450 reductase and lipid. The turnover number was calculated as
      4.2 nmol HCOH/(min nmol P450). Overall, these results show that P4503A and P4502B
      are the major P450s responsible for N-demethylation of cocaine, whereas
      contribution of P4502D is a minor one, and P4502E1 is not involved in the N
      demethylation of cocaine in mullet liver microsomes.

PMID- 12815614
TI  - Prophylactic protection by N-acetylcysteine against the pulmonary injury induced
      by 2-chloroethyl ethyl sulfide, a mustard analogue.
AB  - Mustard gas exposure causes adult respiratory distress syndrome associated with
      lung injury. The purpose of this study was to investigate whether an antioxidant,
      such as N-acetylcysteine (NAC), has any protective effect. Guinea pigs were given
      single exposure (0.5-6 mg/kg body weight) of 2-chloroethyl ethyl sulfide (CEES)
      as a mustard analogue intratracheally and maintained for various lengths of time
      (1 h to 21 days). Within 1 h of CEES infusion at 4 mg/kg, high levels of tumor
      necrosis factor alpha (TNF-alpha), ceramides, and nuclear factor kappaB
      accumulated in lung and alveolar macrophages. Both acid and neutral
      sphingomyelinases were activated within 4 h. These signal transduction events
      were associated with alteration in the oxygen defense system. Within 1 h of
      exposure to CEES (6 mg/kg body weight), there was 10-fold increase in the (125)I
      BSA leakage into lung tissue, indicating severe lung injury. Although low level
      of CEES exposure (0.5 mg/kg body weight) produced symptoms of chemical burn in
      lung as early as 1 h after exposure, the severity of edema, congestion,
      hemorrhage, and inflammation increased progressively with time (1 h to 21 days).
      Feeding of single dose of NAC (0.5 g) by gavage just before the CEES infusion was
      ineffective to counteract these effects. However, consumption of the antioxidant
      in drinking water for 3 or 30 days prior to CEES exposure significantly inhibited
      the induction of TNF-alpha, activation of neutral and acid sphingomyelinases,
      production of ceramides, activation of caspases, leakage of (125)I-bovine serum
      albumin ((125)I-BSA) into lung tissue, and histological alterations in lung.
      Pretreatment with NAC for 3 and 30 days protected against 69-76% of the acute
      lung injury. Therefore, NAC may be an antidote for CEES-induced lung injury.

PMID- 12815615
TI  - Comparative effects of herbicide dicamba and related compound on plant
      mitochondrial bioenergetics.
AB  - The herbicide dicamba (3,6-dichloro-2-methoxybenzoic acid) was evaluated for its
      effects on bioenergetic activities of potato tuber mitochondria to elucidate
      putative mechanisms of action and to compare its toxicity with 2-chlorobenzoic
      acid. Dicamba (4 micro mol/mg mitochondrial protein) induces a limited
      stimulation of state 4 respiration of ca. 10%, and the above concentrations
      significantly inhibit respiration, whereas 2-chlorobenzoic acid maximally
      stimulates state 4 respiration (ca. 50%) at about 25 micro mol/mg mitochondrial
      protein. As opposed to these limited effects on state 4 respiration,
      transmembrane electrical potential is strongly decreased by dicamba and 2
      chlorobenzoic acid. Dicamba (25 micro mol/mg mitochondrial protein) collapses,
      almost completely, Deltapsi; similar concentrations of 2-chlorobenzoic acid
      promote Deltapsi drops of about 50%. Proton permeabilization partially
      contributes to Deltapsi collapse since swelling in K-acetate medium is
      stimulated, with dicamba promoting a stronger stimulation. The Deltapsi decrease
      induced by dicamba is not exclusively the result of a stimulation on the proton
      leak through the mitochondrial inner membrane, since there was no correspondence
      between the Deltapsi decrease and the change on the O(2) consumption on state 4
      respiration; on the contrary, for concentrations above 8 micro mol/mg
      mitochondrial protein a strong inhibition was observed. Both compounds inhibit
      the activity of respiratory complexes II and III but complex IV is not
      significantly affected. Complex I seems to be sensitive to these xenobiotics. In
      conclusion, dicamba is a stronger mitochondrial respiratory chain inhibitor and
      uncoupler as compared to 2-chlorobenzoic acid. Apparently, the differences in the
      lipophilicity are related to the different activities on mitochondrial
      bioenergetics.

PMID- 12815616
TI  - Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced
      diabetic rats.
AB  - Free radicals and oxidative stress have been implicated in the etiology of
      diabetes and its complications. This in vivo study has examined whether subacute
      administration of pycnogenol, a French pine bark extract containing procyanidins
      that have strong antioxidant potential, alters biomarkers of oxidative stress in
      normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a
      single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after
      30 days) in subnormal body weight, increased serum glucose concentrations, and an
      increase in liver weight, liver/body weight ratios, total and glycated
      hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic
      rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days.
      Pycnogenol treatment significantly reduced blood glucose concentrations in
      diabetic rats. Biochemical markers for oxidative stress were assessed in the
      liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was
      restored to normal levels after pycnogenol treatment. Additionally, diabetic rats
      treated with pycnogenol had significantly elevated levels of reduced glutathione
      and glutathione redox enzyme activities. The results demonstrate that pycnogenol
      alters intracellular antioxidant defense mechanisms in streptozotocin-induced
      diabetic rats.

PMID- 12815617
TI  - Cathepsin L plays an active role in involution of the mouse mammary gland.
AB  - Involution of the mammary gland after weaning occurs in two stages. The first
      stage is reversible, whereas the second stage is characterized by the
      irreversible collapse of the alveolar structure. A differential display analysis
      using cDNAs from tissues obtained at various times after forced weaning of pups
      identified cathepsin L as up-regulated during early involution. Levels of
      cathepsin L mRNA were dramatically increased within 24 hr after weaning.
      Cathepsin L protein detected by immunoblot was also increased during involution,
      reaching near maximal levels by 36 hr after weaning. In situ immunohistochemistry
      detected pronounced cathepsin L protein in the cytoplasm and cell periphery. Mice
      treated with a specific inhibitor of cathepsin L exhibited substantially reduced
      numbers of apoptotic cells at times up to 72 hr after weaning when compared with
      untreated animals. The cathepsin L inhibitor did not alter levels of cathepsin L
      detected in immunoblots or influence molecular weight of the cathepsin L species
      detected. These data suggest that cathepsin L plays a regulatory role early in
      the process of mammary gland involution.

PMID- 12815618
TI  - Characterization of Wnt signaling components and activation of the Wnt canonical
      pathway in the murine retina.
AB  - The neuroepithelial layer of the developing eyecup contains multipotential
      precursor cells that give rise to all of the neurons and the one glial cell type
      present in the adult retina. Patterning within the retinal neuroepithelium is
      regulated by cell intrinsic as well as cell extrinsic mechanisms. Although the
      identity of some of the signaling molecules that regulate retinal development is
      known, the function of many others, especially members of the Wnt family, has yet
      to be characterized in the context of retinal development. We undertook a
      comprehensive in situ hybridization analysis to examine the expression of Wnt
      pathway components in the developing and adult mouse neural retina. Our findings
      confirm and extend previous expression studies in mice and other vertebrates, as
      we show that Wnt-3, -5a, -5b, and -7b are expressed in the neural retina and that
      there is a dynamic pattern of Wnt receptor (Mouse frizzled [Mfz]) and Wnt
      antagonist (Secreted-frizzled-related protein [Sfrp]) gene expression in the
      embryonic and perinatal neural retina. Moreover, we show that Wnt-13 is expressed
      in the pigment epithelium overlying the distal part of the eyecup and the ciliary
      margin and that Mfz-4, -6, and -7 are expressed in different regions within the
      ciliary margin. To determine where activation of canonical Wnt signaling is
      occurring in the retina, we examined reporter gene expression in TCF/Lef-LacZ
      mice and we demonstrate that the highest levels of beta-gal activity are found in
      the ciliary margin, adjacent to and within the Wnt-13 expression domain,
      implicating Wnt-13 signaling in the development of the ciliary margin and its
      derivatives.

PMID- 12815619
TI  - Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated
      premature cranial suture closure.
AB  - Cranial sutures are an important growth center of the cranial bones, and the
      suture space must be maintained to permit the cranial adjustments needed to
      accommodate brain growth. Craniosynostosis, characterized by premature suture
      closure, mainly results from mutations that generate constitutively active
      fibroblast growth factor (FGF) receptors. FGF signaling, thus, is responsible for
      the pathogenesis of craniosynostosis. Even though FGF activates many different
      signaling pathways, the one involved in premature suture closure has not been
      defined. We observed that placing FGF2-soaked bead on the osteogenic fronts of
      cultured mouse calvaria accelerates cranial suture closure and strongly induces
      the expression of osteopontin, an early marker of differentiated osteoblasts.
      FGF2 treatment also induced fos and jun mRNAs and later increased the nuclear
      levels of activator protein 1 (AP1). FGF2 stimulates the expression of
      osteopontin by inducing expression of AP1, which then binds to its response
      element in the osteopontin promoter. Blocking of the Erk pathway by PD98059
      suppressed the AP1 and osteopontin expression stimulated by FGF2. Coincidently,
      blocking of the Erk pathway also significantly retarded FGF2-accelerated cranial
      suture closure. Thus, the Erk pathway mediates FGF/FGF receptor-stimulated
      cranial suture closure, probably by stimulating synthesis of AP1 that then
      stimulates the differentiation of osteoblasts.

PMID- 12815620
TI  - 435-bp liver regulatory sequence in the liver fatty acid binding protein (L-FABP)
      gene is sufficient to modulate liver regional expression in transgenic zebrafish.
AB  - Liver fatty acid binding protein (L-FABP) is a small protein that is thought to
      play an important role in the intracellular binding and trafficking of long chain
      fatty acids in the liver. Expression of the gene encoding the zebrafish liver
      fatty acid binding protein is regulated by a 435-bp distal region (-1944 to 
      1510) of the L-FABP promoter. The 435-bp sequence is sufficient for gene
      activation in the liver primordia (or bud) and continues to be active in the
      adult liver when positioned adjacent to the SV40 basal promoter and linked
      directly to green fluorescent protein. The 435-bp sequence region has two
      distinct liver regulatory elements, A (-1944 to -1623) and B (-1622 to -1510),
      and contains multiple putative consensus binding sites. The element A sequence
      includes two consensus HFH and one HNF-1alpha site and the element B sequence
      includes one consensus HNF-3beta site. Deletion of an internal 435-bp fragment (
      1944 to -1510) including the A and B elements totally ablated the liver-specific
      activity of the zebrafish L-FABP gene promoter. Deletion of either of the two
      elements reduces the liver activity. Mutation of the HNF-1alpha site or either of
      the two HFH sites in the A element or the HNF-3beta site in the B element
      significantly altered specificity in the liver primordia of transient expression
      embryos. The importance of the HNF-1alpha consensus binding site in the A element
      and the HNF-3beta consensus binding site in the B element within the 435-bp
      distal region of the L-FABP promoter region suggests that combinatorial
      interactions between multiple regulatory factors are responsible for the gene
      expression of L-FABP in the liver.

PMID- 12815621
TI  - Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1)
      during mouse gonad development.
AB  - In mammals, the gene Sry initiates signaling pathways triggering the
      differentiation of a testis from a sexually indifferent gonad. Assuming that
      these morphogenetic events may alter the proteolytic balance, the expression of
      matrix metalloproteinases (MMPs) and inhibitors (TIMPs) was investigated in
      gonads from 11.5 days postcoitum (dpc) onward, when testicular organogenesis
      occurs. Whereas selective MMPs and TIMPs (1-3) were detected in undifferentiated
      gonads (11.5 dpc) and in neonatal testes, a single TIMP (TIMP-1) was expressed in
      a sexually dimorphic manner from 12.5 dpc onward (i.e., after overt male gonad
      differentiation), demonstrated by using a semiquantitative reverse transcriptase
      polymerase chain reaction and a Western blot analysis. To gain insight into the
      role of TIMP-1, the expression of gelatinases (mRNA levels and enzyme activity)
      was monitored. However, no sex differences could be evidenced, indicating that
      TIMP-1 was not inhibiting this class of MMPs during testis organogenesis. Apart
      from being an inhibitor of MMPs, TIMP-1 is known to display growth promoting
      activities. Of interest, testicular TIMP-1 (but not TIMP-2) levels were further
      enhanced up to 2 weeks of age, consistent with a role in the early postnatal
      testicular growth. We, therefore, established an organotypic culture system in
      which seminiferous cords may differentiate de novo and grow, depending on culture
      conditions. In that system and mimicking the in vivo situation, TIMP-1
      immunolocalized strongly within the male gonadal territory and weakly in female
      gonads, in which no organization was evident. Experiments are now under way to
      determine to what extent TIMP-1 is a morphogenic gene involved in seminiferous
      cord formation and development.

PMID- 12815622
TI  - Perturbed thyroid morphology and transient hypothyroidism symptoms in Hoxa5
      mutant mice.
AB  - The Hox family of transcriptional regulators has been extensively studied for
      their role in axial and appendicular patterning. Genetic analyses have also
      unveiled Hox gene function in organogenesis and postnatal development. A
      phenotypical survey of the Hoxa5(-/-) mutant mice shows that the surviving
      mutants display symptoms of hypothyroidism, including transient growth
      retardation, and delayed eye opening and ear elevation. Thyroid gland
      morphogenesis initiates normally, but follicle formation and thyroglobulin
      processing are abnormal at late gestation. The expression of several molecular
      markers essential for thyroid gland formation and function, namely Nkx2.1, Pax8,
      and Titf2, is affected in the developing thyroid gland of Hoxa5(-/-) mutants. As
      a consequence, the expression of thyroid effector genes, including the
      thyroglobulin and thyroperoxidase genes, is perturbed. Our characterization
      reveals that the loss of Hoxa5 function transiently affects thyroid development
      in a non-cell autonomous manner.

PMID- 12815623
TI  - Hoxb1 neural crest preferentially form glia of the PNS.
AB  - The vertebrate cranial neural crest cells give rise to many complex derivatives
      of the head, neck, and face, including neuronal and glial cells that act in
      concert for proper development of the anterior-peripheral nervous system. Several
      genes have been implicated in the processes of neural crest specification,
      migration, and differentiation; among these are the hox gene clusters. To
      determine the fates of hox-expressing cranial neural crest, we describe the
      results of a genetic lineage analysis by using the Cre/loxP system to drive the
      activation of different ROSA26 reporter alleles under the regulation of the hoxb1
      locus. By targeting the 3' untranslated region of the hoxb1 gene, we have
      preserved endogenous gene activity and have been able to accurately follow the
      fates of the cells derived from the hoxb1 expression domain. Emphasis was placed
      on identifying the cell and tissue types that arise from the rhombomere 4-derived
      neural crest. Our results demonstrate that, in addition to forming much of the
      cartilage, bones, and muscle of the ears and neck, a significant population of
      rhombomere 4-derived neural crest is fated to generate the glial component of the
      seventh cranial nerve.

PMID- 12815624
TI  - TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation
      during palatal fusion.
AB  - Transforming growth factor (TGF) -beta3 is known to selectively regulate the
      disappearance of murine medial edge epithelium (MEE) during palatal fusion.
      Previous studies suggested that the selective function of TGF-beta3 in MEE was
      conducted by TGF-beta receptors. Further studies were needed to demonstrate that
      the TGF-beta signaling mediators were indeed expressed and phosphorylated in the
      MEE cells. SMAD2 and SMAD3 were both present in the MEE, whereas SMAD2 was the
      only one phosphorylated during palatal fusion. SMAD2 phosphorylation was
      temporospatially restricted to the MEE and correlated with the disappearance of
      the MEE. No phosphorylated SMAD2 was found in MEE in TGF-beta3(-/-) mice,
      although nonphosphorylated SMAD2 was present. The results suggest that TGF-beta3
      is required for initiating and maintaining SMAD2 phosphorylation in MEE. Phospho
      SMAD3 was not detectable in palate during normal palatal fusion. Previous results
      suggested TGF-beta-induced cessation of DNA synthesis in MEE cells during palatal
      fusion in vitro. The present results provide evidence that inhibition of MEE
      proliferation in vivo was controlled by endogenous TGF-beta3. The number of 5
      bromo-2'-deoxyuridine (BrdU) -labeled MEE cells was significantly reduced in TGF
      beta3(+/+) compared with TGF-beta3(-/-) mice when the MEE seam formed (t-test, P
      < 0.05). This finding suggests that TGF-beta3 is required for inhibiting MEE
      proliferation during palatal fusion. The inhibition of MEE proliferation may be
      mediated by TGF-beta3-dependent phosphorylation of SMAD2.

PMID- 12815625
TI  - Developmental changes in neurite outgrowth responses of dorsal root and
      sympathetic ganglia to GDNF, neurturin, and artemin.
AB  - The ability of glial cell line-derived neurotrophic factor (GDNF), neurturin, and
      artemin to induce neurite outgrowth from dorsal root, superior cervical, and
      lumbar sympathetic ganglia from mice at a variety of development stages between
      embryonic day (E) 11.5 and postnatal day (P) 7 was examined by explanting ganglia
      onto collagen gels and growing them in the presence of agarose beads impregnated
      with the different GDNF family ligands. Artemin, GDNF, and neurturin were all
      capable of influencing neurite outgrowth from dorsal root and sympathetic
      ganglia, but the responses of each neuron type to the different ligands varied
      during development. Neurites from dorsal root ganglia responded to artemin at P0
      and P7, to GDNF at E15.5 and P0, and to neurturin at E15.5, P0, and P6/7; thus,
      artemin, GDNF, and neurturin are all capable of influencing neurite outgrowth
      from dorsal root ganglion neurons. Neurites from superior cervical sympathetic
      ganglia responded significantly to artemin at E15.5, to GDNF at E15.5 and P0, and
      to neurturin at E15.5. Neurites from lumbar sympathetic ganglia responded to
      artemin at all stages from E11.5 to P7, to GDNF at P0 and P7 and to neurturin at
      E11.5 to P6/7. Combined with the data from previous studies that have examined
      the expression of GDNF family members, our data suggest that artemin plays a role
      in inducing neurite outgrowth from young sympathetic neurons in the early stages
      of sympathetic axon pathfinding, whereas GDNF and neurturin are likely to be
      important at later stages of sympathetic neuron development in inducing axons to
      enter particular target tissues once they are in the vicinity or to induce
      branching within target tissues. Superior cervical and lumbar sympathetic ganglia
      showed temporal differences in their responsiveness to artemin, GDNF, and
      neurturin, which probably partly reflects the rostrocaudal development of
      sympathetic ganglia and the tissues they innervate.

PMID- 12815627
TI  - Isolation of a novel cDNA enriched in the undifferentiated chick retina and lens.
AB  - By using a differential screening strategy, we have identified a previously
      uncharacterised gene that is preferentially expressed in chick retinal precursor
      cells as well as in the anterior epithelial cells of the lens at early stages of
      development. The EURL transcript has an open reading frame of 293 amino acids and
      a 3' untranslated region of >850 nucleotides. The only recognizable feature in
      the EURL (early undifferentiated retina and lens) amino acid sequence is a
      putative coiled-coil domain located at the C-terminus of the protein. The human
      EURL orthologue maps to chromosome 21q21. Northern blot analysis, in situ
      hybridization of tissue sections, and whole-mount hybridization indicate elevated
      levels of EURL mRNA in the embryonic dorsal retina from stage 14 (day 2) to stage
      18 (day 3). At day 3.5, when >90% of the retinal cells are in the proliferative
      stage, EURL transcripts are found primarily in the peripheral dorsal retina,
      i.e., the most undifferentiated part of the dorsal retina. EURL transcripts are
      also detected in the lens at stage 18 and remain abundant in the proliferating
      epithelial cells of the lens until at least day 11. The distribution pattern of
      EURL in the developing retina and lens suggest a role before the events leading
      to cell determination and differentiation.

PMID- 12815626
TI  - Expression of Sox transcription factors in the developing mouse pancreas.
AB  - Previous work has identified members of the homeodomain and basic helix-loop
      helix families of transcription factors as critical determinants of mammalian
      pancreatic development. Here, we describe the identification of HMG-box
      transcription factors of the Sox gene family in the mouse pancreas. We detected
      transcripts for Sox11, Sox4, Sox13, Sox5, Sox9, Sox8, Sox10, Sox7, Sox17, Sox18,
      Sox15, and Sox30 in embryonic pancreas and found Sox4, Sox9, and Sox13 in adult
      pancreatic islets. Expression of seven of these Sox factors was studied in more
      detail by in situ hybridization from the stage of early pancreatic outgrowth to
      birth. Expression of Sox11 was found in the mesenchyme surrounding the pancreatic
      buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later
      to islets. Sox13 and L-Sox5 showed expression in most of the pancreatic
      epithelial cells between embryonic days 12.5 and 14.5. Sox8 and Sox10 were
      detected in a thin layer of cells surrounding the islets. The expression patterns
      of Sox genes in the embryonic pancreas suggest that they could have important and
      possibly redundant functions in pancreas development.

PMID- 12815629
TI  - Three-dimensional morphology of inner ear development in Xenopus laevis.
AB  - The three-dimensional morphology of the membranous labyrinth of Xenopus laevis is
      presented from embryonic through late tadpole development (stages 28 to 52,
      inclusive). This was accomplished by paint-filling the endolymphatic spaces of
      Xenopus ears at a series of stages, beginning with the embryonic otic vesicle and
      ending with the complex ear of the late tadpole. At stage 52, the inner ear has
      expanded approximately 23-fold in its anterior/posterior dimension compared with
      stage 28 and it is a miniature of the adult form. The paint-filling technique
      illustrates the dramatic changes required to convert a simple ear vesicle into
      the elaborate form of the adult, including semicircular canal formation and
      genesis of vestibular and auditory organs, and it can serve as a basis for
      phenotype identification in experimentally or genetically manipulated ears.

PMID- 12815628
TI  - AMPA-evoked ion influx is strongest in tangential neurons of the rat neocortical
      intermediate zone close to the front of the migratory stream.
AB  - In addition to the classically described radially migrating neurons, embryonic
      cortical areas receive neurons originating from the basal ganglia. One of the
      migration routes is in the intermediate zone. The front of this migration moves
      toward the hippocampus synchronously with the edge of the dorsally extending
      cortical plate. We investigated whether cells close to the front have specific
      properties compared with those at less advanced positions. Activation of AMPA
      receptors in the presence of cobalt showed that a strong influx of divalent
      cations could be triggered in front cells by low agonist concentration, whereas
      the less advanced cells needed a higher concentration to incorporate detectable
      amounts of cobalt. As shown by in situ hybridization, this discrepancy was not
      due to differential expression of GluR-2 (known to reduce permeability for
      divalent cations). In vivo, release of an endogenous agonist presumably affects
      more, or differently, the tangential cells close to the front.

PMID- 12815630
TI  - Expression patterns of Tgfbeta1-3 associate with myocardialisation of the outflow
      tract and the development of the epicardium and the fibrous heart skeleton.
AB  - Transforming growth factor-beta (Tgfbeta) is essential for normal embryogenesis.
      The cardiac phenotypes obtained after knockout of each of the three mammalian
      isoforms suggest different roles during morphogenesis. We studied cardiovascular
      expression of Tgfbeta1-3 in parallel tissue sections of normal mouse embryos from
      9.5 to 15.5 days post coitum (dpc) by using radioactive in situ hybridisation.
      The Tgfbeta isoforms are differentially expressed in unique and in overlapping
      patterns during cardiovascular development. In the vessels, Tgfbeta1 is found in
      the intima, whereas Tgfbeta2 and -beta3 are mainly present in the media and
      adventitia of the great arteries. Tgfbeta1 is present in the endocardium at all
      stages examined. The Tgfbeta2 signal in the endocardium of the atrioventricular
      canal and outflow tract (9.5 dpc) shifts during epithelial-mesenchymal
      transformation toward the mesenchymal cushions (10.5-11.5 dpc) after which it
      exhibits a marked spatiotemporal expression pattern as the cushion
      differentiation progresses (11.5-15.5 dpc). The myocardium underlying the
      endocardial cushions and the atrial muscular septum are intensely positive for
      Tgfbeta2 at early stages (9.5-11.5 dpc) and expression decreases at 12.5 days. In
      contrast to earlier reports, we find marked overlap of Tgfbeta2 and -beta3
      expression. Tgfbeta3 expression shows a characteristic distribution in the
      mesenchymal cushions, suggesting a role in cushion differentiation, possibly
      additional to Tgfbeta2. From 14.5 dpc onward, a strong Tgfbeta3 signal is found
      in the fibrous septum primum of the atrium and in the fibrous skeleton of the
      heart. Special attention was paid to the proepicardial organ and its derivatives.
      The proepicardial organ strongly expresses Tgfbeta2 as early as 9.5 days, and all
      isoforms are present in the epicardium from 12.5 dpc onward. The spatiotemporal
      cardiovascular expression of Tgfbeta1-3 supports both specific and complementary
      functions during cardiovascular development that might explain functional
      redundancy between the Tgfbeta-isoforms. The information provided favors novel
      roles of Tgfbeta1-3 in epicardial development, of Tgfbeta2 in myocardialisation,
      and of Tgfbeta3 in differentiation of the fibrous structures of the heart.

PMID- 12815631
TI  - Expression of MRF4 protein in adult and in regenerating muscles in Xenopus.
AB  - In Xenopus, previous studies showed that the transcripts of the myogenic
      regulatory factor (MRF) MRF4 accumulate during skeletal muscle differentiation,
      but nothing is known about the accumulation of XMRF4 protein during myogenesis.
      In this report, an affinity-purified polyclonal antibody against Xenopus MRF4 was
      developed and used to describe the pattern of expression of this myogenic factor
      in the adult and in regenerating muscles. From young forming myotubes, XMRF4
      protein persistently accumulated in nuclei during the regeneration process and
      was strongly expressed in nuclei of adult muscles. No selective accumulation of
      XMRF4 protein was detectable at neuromuscular junctions, but XMRF4
      immunoreactivity was observed in sole plate nuclei as well as in extrasynaptic
      myofiber nuclei. We also report that XMRF4 protein accumulated before the
      establishment of neuromuscular connections, showing that innervation is not
      necessary for the appearance of XMRF4 protein during muscle regeneration.

PMID- 12815632
TI  - Ontogenic expression of TGFbeta 1, 2, and 3 and its receptors in the rat gastric
      mucosa.
AB  - The stomach of the rat undergoes extensive changes during the formation and
      maturation of gastric glands. The presence of transforming growth factor beta
      (TGFbeta) in rat milk and in the gastrointestinal tract of pups may suggest its
      role in this process. The current study evaluated the in vivo dynamic expression
      and distribution of TGFbeta1, beta2, beta3 and their receptors TbetaRI and
      TbetaRII in the gastric epithelium of 20-day fetal rats and 1-, 14-, 21-, and 30
      day-old pups. Immunohistochemistry was used to detect the proteins, and staining
      was classified according to intensity and cell type. The results showed that the
      gastric epithelium expresses TGFbeta isoforms and receptors throughout
      development. We found that immunoreactivity paralleled the appearance of
      differentiated cells, such that surface mucous cells were the first to be
      immunostained and chief cells were the last. The intensity of reactions followed
      this same pattern, showing that the expression of TGFbeta isoforms spread along
      the gland with growth. Of interest, the highest apparent activity of TGFbeta was
      observed from 21 days onward, a period that is concomitant with weaning and
      maturation of most gastric cell types. In addition, surface mucous cells were
      strongly labeled at the basal cytoplasm at 14 days, suggesting an interaction
      with the connective tissue. In conclusion, the dynamic expression of TGFbeta1,
      beta2, beta3, and TbetaRI and TbetaRII through stomach development suggests
      significant paracrine and autocrine roles for this growth factor. We propose that
      temporal and spatial differences may be regulated by dietary changes, which in
      turn control cell proliferation and differentiation in the gastric epithelium.

PMID- 12815633
TI  - Chronological gene expression of ADAMs during testicular development:
      prespermatogonia (gonocytes) express fertilin beta (ADAM2).
AB  - Immediately after birth, primordial germinal cell-derived prespermatogonia (PSG),
      located in the center of the testicular cords, migrate between adjacent Sertoli
      cells to establish contact with the cord basal lamina. PSG migration suggests
      continued assembly and disassembly of cell-cell contacts by a molecular mechanism
      that may involve integrins and their ligands, the disintegrin domain of
      spermatogenic cell-specific plasma membrane proteins called ADAMs. We have
      analyzed the temporal gene expression of selected ADAMs in intact fetal, early
      postnatal, and pubertal rat testis and Sertoli-spermatogenic cell cocultures by
      reverse transcriptase-polymerase chain reaction, in situ hybridization, and
      immunocytochemistry. We report that several ADAM transcripts are expressed in
      fetal, neonatal, and prepubertal testes. Cyritestin (ADAM3), ADAM5, ADAM6, and
      ADAM15 are expressed in day 17 fetal testes. In contrast, no expression of
      fertilin alpha (ADAM1) and fertilin beta (ADAM 2) was detected in fetal testes.
      Fertilin beta gene expression starts after postnatal day 2, subsequent to the
      expression of fertilin alpha, which occurs on postnatal day 1. After postnatal
      day 2, all the indicated ADAMs, including the fertilin alpha and fertilin beta,
      continue to be expressed. Transcripts of spermatogenic cell-specific fertilin
      alpha, fertilin beta, ADAM3, and ADAM5 were detected during the coculture of PSG
      with Sertoli cells for up to 72 hr after plating. The presence of fertilin beta
      mRNA and protein in cocultured PSG was visualized by in situ hybridization and
      immunocytochemistry, respectively. These observations indicate that PSG in
      coculture with Sertoli cells provide a suitable approach for analyzing cell-cell
      adhesive responses involving spermatogenic cell-specific ADAMs.

PMID- 12815634
TI  - Functional magnetic resonance imaging: a review of methodological aspects and
      clinical applications.
AB  - This paper gives an overview of the recent literature on methodological
      developments of functional magnetic resonance imaging (fMRI) and recent trends in
      clinical applications. With the recent introduction of high-field systems and
      methodological developments leading to more robust signal behavior, fMRI is in a
      transition state from a research modality for use by experts to a standard
      procedure with useful applications in patient management. Compared to the use in
      neuroscientific research, which is often based on BOLD techniques alone, the
      application in patients is distinguished by a multiparametric characterization of
      the brain using a combination of several techniques. Neuronal fiber tracking
      based on diffusion anisotropy measurements, in particular, has already turned out
      to provide relevant supplementary information to the BOLD-based cortical
      activation maps.

PMID- 12815635
TI  - Methodological considerations for measuring rates of brain atrophy.
AB  - PURPOSE: To systematically compare two techniques for measuring brain atrophy
      rates from serial magnetic resonance imaging (MRI) studies. MATERIALS AND
      METHODS: Using the separation in atrophy rate between cohorts of cognitively
      normal elderly subjects and patients with Alzheimer's disease (AD) as the gold
      standard, we evaluated 1) different methods of computing volume change; 2)
      different methods for steps in image preprocessing-intensity normalization,
      alignment mask used, and bias field correction; 3) the effect of MRI acquisition
      hardware changes; and 4) the sensitivity of the method to variations in initial
      manual volume editing. For each of the preceding evaluations, measurements of
      whole-brain and ventricular atrophy rates were calculated. RESULTS: In general,
      greater separation between the clinical groups was seen with ventricular rather
      than whole-brain measures. Surprisingly, neither the use of bias field correction
      nor a major hardware change between the scan pairs affected group separation.
      CONCLUSION: Atrophy rate measurements from serial MRI are candidates for use as
      surrogate markers of disease progression in AD and other dementing
      neurodegenerative disorders. The final method has excellent precision and
      accurately captures the expected biology of AD-arguably the two most important
      features if this technique is to be used as a biomarker of disease progression.

PMID- 12815636
TI  - Comparison of right ventricular volume measurements between axial and short axis
      orientation using steady-state free precession magnetic resonance imaging.
AB  - PURPOSE: To compare right ventricular (RV) volume measurements and their
      reproducibility between axial and short axis orientation acquisition techniques.
      MATERIALS AND METHODS: Measurements of RV volumes from data sets acquired in
      axial and short axis orientations were compared in 20 normal subjects. The
      observer variabilities were assessed and the left ventricle (LV) and RV stroke
      volumes (SV) were compared. RESULTS: There was a significant and systematic
      difference in the EDV and ESV volumes between the axial and short axis methods.
      The latter method resulted in larger volumes (mean bias EDV 7.5 +/- 13.2, 4.7%
      difference; ESV 7.2 +/- 8.6, 10.7% difference). The axial method had lower intra-
      and interobserver variability than the short axis method. The standard deviation
      of the difference (SDD) and the limits of agreement were consistently lower for
      the axial method. The mean differences between LV and RV stroke volumes expressed
      as mean +/- 1 SD (r(2) =correlation coefficient) were: axial 7.6 +/- 9.1 (r(2) =
      0.93); and short axis 7.4 +/- 10.8 (r(2) = 0.90). CONCLUSION: There is a
      significant systematic difference between volumes measured using the two
      different orientations. The axial orientation resulted in better inter- and
      intraobserver reproducibility.

PMID- 12815637
TI  - A single breath-hold multiecho T2* cardiovascular magnetic resonance technique
      for diagnosis of myocardial iron overload.
AB  - PURPOSE: To assess tissue iron concentrations by the use of a gradient echo T2*
      multiecho technique. MATERIALS AND METHODS: We compared the results of
      measurements of heart T2* from 32 patients using the established multiple breath
      hold variable TR technique with a new multiecho sequence that acquires all images
      within a single breath-hold with constant TR. RESULTS: There was good agreement
      of myocardial T2* values between both methods in the abnormal range of T2* < 20
      msec (mean difference 0.2 msec, 95% CI -1.3 to 0.9 msec, r = 0.97, P < 0.0001).
      The coefficient of variability between the methods was 3.5%. The interstudy
      reproducibility using the multiecho sequence had a variability coefficient of
      2.3% in the abnormal T2* range and 5.8% over all T2* values. There was good
      agreement between the techniques for the liver T2* values. CONCLUSIONS: The use
      of the single breath-hold, multiecho acquisition allowed reliable quantification
      of myocardial T2*. The good reproducibility, speed, and T1 independence of this
      technique allows greater accuracy, faster patient throughput, and, therefore,
      reduced costs (which is important in developing countries where thalassemia is
      most prevalent).

PMID- 12815639
TI  - High signal peripancreatic fat on fat-suppressed spoiled gradient echo imaging in
      acute pancreatitis: preliminary evaluation of the prognostic significance.
AB  - PURPOSE: To evaluate peripancreatic signal changes on fat-suppressed T1-weighted
      spoiled gradient echo images associated with acute pancreatitis and investigate
      potential utility in regards to relationship to clinical outcome. MATERIALS AND
      METHODS: The abdominal MR images in 31 patients with acute pancreatitis were
      reviewed, and evaluated for the presence of elevated signal intensity within the
      peripancreatic fat on fat-suppressed T1-weighted spoiled gradient echo images;
      the degree of signal changes was graded as mild, moderate, or severe. RESULTS:
      Ten of 31 patients demonstrated abnormal high signal intensity in the
      peripancreatic fat on fat-suppressed T1-weighted images. The degree of signal
      change was mild in three patients, moderate in one, and severe in six patients.
      All six patients with severe elevated peripancreatic soft tissue signal died
      within seven to 68 days (mean, 47 days) of their admission. All 21 patients
      without elevated peripancreatic fat signal survived without any complications.
      The correlation between the presence and severity of elevated peripancreatic MR
      signal and patient outcome was significant (P < 0.05). CONCLUSION: Elevated
      peripancreatic signal on fat-suppressed T1-weighted images is associated
      progressively with poor outcome in patients with acute pancreatitis, and may
      represent a simplified method for prognostic cross-sectional imaging.

PMID- 12815638
TI  - Perilesional hyperintense rim of malignant hepatic tumors on ferumoxide-enhanced
      T1-weighted gradient-echo MR images: correlation between MR imaging and
      histopathologic findings.
AB  - PURPOSE: To correlate the perilesional hyperintense rim of malignant hepatic
      tumors seen on ferumoxide-enhanced T1-weighted gradient-echo (GE) MR images with
      histopathologic findings. MATERIALS AND METHODS: In 13 tumors in 12 patients, T1
      weighted GE images (TE of 1.4 msec, flip angle of 90 degrees) obtained after IV
      administration of ferumoxide were evaluated. MR imaging was initiated within one
      hour of the completion of ferumoxide administration. Surgical resection for
      tumors was performed within an interval of two weeks of the MR imaging. Resected
      specimens were histopathologically examined for peritumoral sinusoidal
      congestion, desmoplastic reaction, compressed hepatic parenchyma, lymphocytic
      infiltration, and vascular proliferation. RESULTS: In twelve tumors (92%),
      prominently (N = 2), moderately (N = 5), and mildly to minimally (N = 5), a
      perilesional hyperintense rim was observed. Among histopathologic findings, the
      degree of peritumoral sinusoidal congestion correlated (R =.75, P <.04) with the
      degree of perilesional hyperintense rim. The thickness of the perilesional
      hyperintense rim showed a moderate positive correlation (R =.65, P <.02) with the
      thickness of peritumoral area with sinusoidal congestion. CONCLUSION:
      Perilesional hyperintense rim of malignant hepatic tumors on ferumoxide-enhanced
      T1-weighted GE images may correlate with sinusoidal congestion surrounding
      malignant hepatic tumors.

PMID- 12815641
TI  - Imaging of the articular cartilage in osteoarthritis of the knee joint: 3D
      spatial-spectral spoiled gradient-echo vs. fat-suppressed 3D spoiled gradient
      echo MR imaging.
AB  - PURPOSE: To compare three-dimensional (3D) spatial-spectral (SS) spoiled gradient
      recalled acquisition in the steady state (SPGR) imaging with fat-suppressed 3D
      SPGR sequences in MR imaging of articular cartilage of the knee joint in patients
      with osteoarthritis. MATERIALS AND METHODS: MR images of six patients with
      osteoarthritis of the knee were prospectively examined with a 1.5T MR scanner.
      For quantitative analyses, the signal-to-noise ratios, contrast-to-noise ratios,
      and contrast of cartilage and adjacent structures including meniscus, synovial
      fluid, muscle, fat tissue, and bone marrow were measured. RESULTS: In patients
      with osteoarthritis, 3DSS-SPGR images demonstrated higher spatial resolution and
      higher mean signal-to-noise (S/N) ratios (cartilage, 24.9; synovial fluid, 12.3;
      muscle, 20.7; meniscus, 21.6), with shorter acquisition times (7 minutes 20
      seconds), when compared to fat-suppressed 3D SPGR images (cartilage, 22.3;
      synovial fluid, 10.8; muscle, 16.7; meniscus, 13.4). CONCLUSION: 3DSS-SPGR
      imaging is a promising method for evaluating cartilage pathology in patients with
      osteoarthritis of the knee and has the potential to replace fat-suppressed 3D
      SPGR imaging.

PMID- 12815640
TI  - High-resolution three-dimensional MR angiography of rodent tumors: morphologic
      characterization of intratumoral vasculature.
AB  - PURPOSE: To evaluate high-resolution three-dimensional MR angiography (MRA) for
      the visualization and morphologic characterization of intratumoral vasculature.
      MATERIALS AND METHODS: Two subcutaneous rodent tumor models (human skin carcinoma
      HaCaT-ras-A-5RT3 grown in nude mice and rat prostate carcinoma R3327-AT1 grown in
      Copenhagen rats) were examined with a clinical 1.5 T MR-system. For MRA a
      dedicated high-resolution three-dimensional gradient echo pulse sequence with a
      voxel size of 166 x 206 x 320 microm(3) was performed after injection of Gadomer
      17. The image analysis included a correlation of intratumoral vessels with
      histology. Signal intensity measurements were performed in the vena cava, the
      tumor underlying muscle, and in various regions of the tumor. Signal-to-noise
      ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated from this
      measurement. RESULTS: High-resolution MRA allowed a clear distinction of
      intratumoral blood vessels. The mouse tumor model tended to be strongly
      vascularized with several intratumoral blood vessels clearly displayed by MRA.
      When correlated with histology, these intratumoral blood vessels had a size in
      the range of 300 to 400 microm. In contrast, rat tumors had only sparse capillary
      intratumoral blood vessels that could only be demonstrated by histology. In both
      tumor models, dilated blood vessels were observed in the subcutaneous tissue near
      the tumor. In general, areas with a strong contrast enhancement correlated with
      viable, well vascularized tumor regions, whereas non-enhancing tumor areas
      correlated with tumor necrosis or hypoxic areas. CONCLUSION: High-resolution
      three-dimensional MRA allows the visualization of intratumoral vasculature in
      rodent models. With minimal hardware and software modifications, high-resolution
      MRA could be performed on a clinical 1.5 T MRI scanner. Morphologic
      characterization of intratumoral blood vessels could add important insights into
      the process of tumor angiogenesis.

PMID- 12815642
TI  - Acromiohumeral distance in a seated position in persons with impingement
      syndrome.
AB  - PURPOSE: To compare the acromiohumeral distance (AHD) of both shoulders in
      subjects with a unilateral shoulder impingement syndrome (SIS) and healthy
      subjects in a seated position during free shoulder movements of large amplitude.
      MATERIALS AND METHODS: Using a 0.5-Tesla SIGNA-SP/i trade mark open-configuration
      magnetic resonance imaging (MRI) system, the AHD was measured at several arm
      positions, in a standardized seated position. RESULTS: In flexion (rest to 130
      degrees ), the mean AHD of SIS varied from 8.3 to 2.8 mm, as compared to from 8.7
      to 4.1 mm for asymptomatic contralateral shoulders. In abduction (rest to 110
      degrees ), the AHD varied from 8.1 to 3.4 mm and from 8.8 to 4.6 mm for SIS and
      asymptomatic shoulders, respectively. The smallest AHD (P <.01) was observed at
      110 degrees. From 80 degrees of arm elevation, the AHD was significantly smaller
      in impingement than in asymptomatic shoulders (P <.05). The AHD of asymptomatic
      shoulders did not differ from that of healthy subjects. In SIS, the AHD at rest
      was correlated with its reduction at all shoulder positions (r(p) = 0.62-0.88),
      but was a poor predictor of the smallest AHD observed at 110 degrees (flexion,
      R(2) = 0.09; abduction, R(2) = 0.08). CONCLUSION: In the critical arm elevation
      positions for impingement, AHD is discriminative for SIS, compared to
      asymptomatic shoulders and healthy ones. AHD at rest is a good indicator of the
      magnitude of its reduction in elevation, but not of the smallest AHD in arm
      elevation.

PMID- 12815644
TI  - Three-dimensional method for comparing in vivo interventional MR images of
      thermally ablated tissue with tissue response.
AB  - PURPOSE: To investigate the ability of magnetic resonance (MR) to monitor radio
      frequency (RF) ablation treatments by comparing MR images of thermal lesions to
      histologically assayed cellular damage. We developed a new methodology using
      three-dimensional registration for making spatial correlations. MATERIALS AND
      METHODS: A low-field, open MRI system was used to guide an ablation probe into
      rabbit thigh muscle and acquire MR volumes after ablation. After fixation, we
      sliced and photographed the tissue at 3-mm intervals, using a specially designed
      apparatus, to obtain a volume of tissue images. Histologic samples were digitized
      using a video microscopy system. For our three-dimensional registration method,
      we used the tissue images as the reference, and registered histology and MR
      images to them using two different computer alignment steps. First, the MR volume
      was aligned to the volume of tissue images by registering needle fiducials placed
      near the tissue of interest. Second, we registered the histology images with the
      tissue images using a two-dimensional warping technique that aligned internal
      features and the outside boundary of histology and tissue images. RESULTS: The MR
      and histology images were very well aligned, and registration accuracy,
      determined from displacement of needle fiducials, was 1.32 +/- 0.39 mm (mean +/-
      SD), which compared favorably to the MR voxel dimensions (0.70 mm in-plane and
      3.0 mm thick). A preliminary comparison of MR and tissue response showed that the
      region inside the elliptical hyperintense rim in MR closely corresponds to the
      region of necrosis as established by histology, with a mean absolute distance
      between MR and histology boundaries of 1.17 mm, slightly smaller than the mean
      registration error. The MR region slightly overestimated the region of necrosis,
      with a mean signed distance between boundaries of 0.85 mm. CONCLUSION: Our
      results suggest that our methodology can be used to achieve three-dimensional
      registration of histology and in vivo MR images. In MR lesion images, the inner
      border of the hyperintense region corresponds to the border of irreversible cell
      damage. This is good evidence that during RF ablation treatments, iMRI lesion
      images can be used for real-time feedback.

PMID- 12815643
TI  - Accelerated dynamic MR imaging with a parallel imaging technique for
      hypervascular hepatocellular carcinomas: usefulness of a test bolus in
      examination and subtraction imaging.
AB  - PURPOSE: To assess the impact of the accelerated dynamic MR imaging (ADMRI)
      approach using parallel imaging for detecting hypervascular hepatocellular
      carcinomas (HCCs) and to evaluate the usefulness of a test bolus in examination
      and subtraction imaging in this setting. MATERIALS AND METHODS: Thirty patients
      with 135 HCCs underwent ADMRI using a two-dimensional gradient-recalled echo
      sequence with parallel imaging. Seventeen patients were evaluated without a test
      bolus and 13 patients with a test bolus. The detectability of HCCs was calculated
      between the groups with and without a test bolus. ADMRI was evaluated regarding
      the signal-to-noise ratio (SNR) of the lesion and the liver, the contrast-to
      noise ratio (CNR) of the lesion vs. the liver, and the feasibility of subtraction
      images. RESULTS: ADMRI with and without a test bolus had almost equal sensitivity
      (92.5% and 92.6%). No significant difference was seen in the SNR of lesions and
      the CNR of lesions vs. livers between both groups. With a test bolus, ADMRI could
      depict the peak enhancement of nodules on the 2nd or 3rd dynamic phases and
      optimized the timing of peak lesion enhancement. Subtraction images could be
      obtained regarding minimal slice misregistration. CONCLUSION: ADMRI had high
      detectability of HCCs with and without a test bolus.

PMID- 12815645
TI  - Keyhole Dixon method for faster, perceptually equivalent fat suppression.
AB  - PURPOSE: To reduce the acquisition time associated with the two-point Dixon fat
      suppression technique by combining a keyhole in-phase (Water + Fat) k-space data
      set with a full out-of-phase (Water - Fat) k-space data set and optimizing the
      keyhole size with a perceptual difference model. MATERIALS AND METHODS: A set of
      keyhole Dixon images was created by varying the number of lines in the keyhole
      data set. Off-resonance correction was incorporated into the image reconstruction
      process to improve the homogeneity of the fat suppression. A perceptual
      difference model (PDM) was validated with human observer experiments and used to
      compare the keyhole images to images from a full two-point Dixon acquisition. The
      PDM was used to determine the smallest keyhole width required to obtain
      perceptual equivalence to images obtained from the full two-point Dixon method.
      RESULTS: In experimental phantom studies, the keyhole Dixon image reconstructed
      from 96 of 192 Water + Fat k-space lines and 192 Water - Fat k-space lines was
      perceptually equivalent to the full (192 + 192) two-point Dixon images, resulting
      in a 25% reduction in scan time. Clinical images of a volunteer's knee, orbits,
      and abdomen created from the smallest, perceptually equivalent keyhole width
      resulted in a 27%-38% reduction in total scan time. CONCLUSION: This method
      improves the temporal efficiency of the conventional two-point Dixon technique
      and may prove especially useful for high-field systems where specific absorption
      rate (SAR) limits will constrain radiofrequency (RF)-based fat suppression
      techniques.

PMID- 12815646
TI  - Dynamic T1 estimation of brain tumors using double-echo dynamic MR imaging.
AB  - PURPOSE: To assess the clinical utility of a new method for real-time estimation
      of T1 during the first pass of contrast agent by using this method to examine
      brain tumors. MATERIALS AND METHODS: The multi-phase spoiled gradient-echo pulse
      sequence using the double-echo magnetic resonance (MR) technique was modified. In
      the first half of the pulse sequence, the flip angle was varied systematically.
      Then, static T1 values were calculated using differences in MR signal intensities
      between different flip angles. In the latter half of this sequence, changes in
      absolute T1 were calculated using differences in signal intensities before and
      after injection of contrast agent. The double-echo MR data were used to minimize
      the T2* effect. Five cases of neurinoma and seven cases of meningioma were
      examined. Changes in T1 during the first pass of contrast agent were compared
      between neurinoma and meningioma. RESULTS: Changes in absolute T1 were clearly
      demonstrated on the parametric map. Although the changes in absolute T1 during
      the first pass of contrast agent did not allow differentiation between the two
      types of tumors, the mean gradient after the first pass was statistically higher
      for neurinoma than for meningioma (P < 0.05; meningioma, 0.011 +/- 0.012 second(
      1)/second; neurinoma, 0.034 +/- 0.020 second(-1)/second). CONCLUSION: The present
      method appears to be useful for estimation of dynamic T1 changes in brain tumors
      in clinical settings.

PMID- 12815647
TI  - The need for phase-encoding flow compensation in high-resolution intracranial
      magnetic resonance angiography.
AB  - PURPOSE: To demonstrate that the time delay between phase and frequency encoding
      and the presence of pulsatile blood flow in high-resolution time-of-flight (TOF)
      imaging of the intracranial arteries (especially near the circle of Willis) can
      distort the appearance of blood vessels and result in a cross-hatch-appearing
      artifact in surrounding tissue. MATERIALS AND METHODS: Two techniques to reduce
      the artifact, tri-directional flow compensation (3DFC) and elliptical-centric
      (EC) phase-encoding order, are investigated in five volunteer studies. RESULTS:
      3DFC eliminates the pulsation-related artifacts and the vessel distortion. A
      residual amplitude variation artifact is observed. EC phase encoding nearly
      eliminates the pulsatile motion-related artifact, but it does not eliminate
      vessel distortion. CONCLUSION: The combination of 3DFC and EC phase encoding
      appears to provide the greatest artifact reduction in the five volunteer studies
      performed.

PMID- 12815648
TI  - Echo planar imaging at 4 Tesla with minimum acoustic noise.
AB  - PURPOSE: To minimize the acoustic sound pressure levels of single-shot echo
      planar imaging (EPI) acquisitions on high magnetic field MRI scanners. MATERIALS
      AND METHODS: The resonance frequencies of gradient coil vibrations, which depend
      on the coil length and the elastic properties of the materials in the coil
      assembly, were measured using piezoelectric transducers. The frequency of the EPI
      readout train was adjusted to avoid the frequency ranges of mechanical
      resonances. RESULTS: Our MRI system exhibited two sharp mechanical resonances (at
      720 and 1220 Hz) that can increase vibrational amplitudes up to six-fold. A small
      adjustment of the EPI-readout frequency made it possible to reduce the sound
      pressure level of EPI-based perfusion and functional MRI scans by 12 dB.
      CONCLUSION: Normal vibrational modes of MRI gradient coils can dramatically
      increase the sound pressure levels during echo planar imaging (EPI) scans. To
      minimize acoustic noise, the frequency of EPI-readout trains and the resonance
      frequencies of gradient coil vibrations need to be different.

PMID- 12815649
TI  - An inductively-coupled, detachable receiver coil system for use with magnetic
      resonance compatible endoscopes.
AB  - PURPOSE: To construct an inductively-coupled receiver coil system for use with a
      magnetic resonance (MR) compatible endoscope, and to evaluate its use in a pilot
      group of patients with esophageal cancer. MATERIALS AND METHODS: An inductively
      coupled coil system, comprising a saddle geometry cylindrical receiver coil
      fitted as a sleeve around the endoscope tip and a pick-up coil housed within a
      channel of an MR-compatible endoscope, was designed and developed for use at 0.5
      T. Twenty-three patients with esophageal cancer were recruited for MR endoscopy.
      In 17 cases, the endoscopic coil system was used in conjunction with an external
      surface coil in order to obtain information from the surrounding mediastinum. The
      examination took 40-50 minutes. RESULTS: MR imaging using the inductively-coupled
      endoscopic coil was successful in 21 cases (one failed intubation and one
      artifact from unrelated external source). Image artifact was largely due to
      respiration and global patient motion in sedated individuals undergoing
      endoscopy. CONCLUSION: Inductively-coupled coil systems may be used with
      endoscopes to allow improved safety through increased patient-system isolation
      and detachability of coils and electronics for repair or replacement with coils
      tuned for different frequencies.

PMID- 12815650
TI  - Spatial excitation using variable-density spiral trajectories.
AB  - PURPOSE: To examine the usefulness of variable-density k-space trajectories for
      the design of multi-dimensional spatially selective RF pulses. MATERIALS AND
      METHODS: Experimental phantom and in vivo studies were performed and confirmed by
      simulations. Two-dimensional spatially selective magnetization patterns were
      excited using variable-density spiral trajectories and analyzed with respect to
      the signal excitation outside the excitation field of view (FOX). RESULTS: By
      using variable-density trajectories, signal excitation outside the FOX was
      drastically reduced compared to trajectories with a uniform density, while
      maintaining fairly short pulse durations. CONCLUSION: A main advantage of the
      method is that unwanted signal excitation outside the nominal FOX can be reduced
      without significantly increasing the duration of the RF excitation pulse. The
      variable-density approach is useful for all applications that require a well
      defined spatial excitation profile, e.g., to perform imaging in a reduced field
      of view (FOV), for spatial saturation pulses, for curved slice imaging or in MR
      spectroscopy.

PMID- 12815651
TI  - Models of Parkinson's disease.
AB  - Parkinson's disease (PD) is a heterogenous disease likely to be caused by more
      than one specific aetiological factor. In rare familial cases of PD with similar
      clinical features to the idiopathic form of the disease, the underlying genetic
      cause has been identified. These PD-associated genes have been manipulated to
      create animal and cell culture models of the disease that have helped to further
      our understanding of the pathogenesis of PD, particularly concerning causes of
      the selective loss of dopaminergic neurons at the molecular level. In addition,
      these models will aid the future development of rational therapeutic strategies.
      This study briefly reviews toxin-induced models and the genetics of PD. It
      focuses on recently developed animal models of PD, as well as in vitro approaches
      to model the disease.

PMID- 12815652
TI  - The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations.
AB  - The Movement Disorder Society Task Force for Rating Scales for Parkinson's
      Disease prepared a critique of the Unified Parkinson's Disease Rating Scale
      (UPDRS). Strengths of the UPDRS include its wide utilization, its application
      across the clinical spectrum of PD, its nearly comprehensive coverage of motor
      symptoms, and its clinimetric properties, including reliability and validity.
      Weaknesses include several ambiguities in the written text, inadequate
      instructions for raters, some metric flaws, and the absence of screening
      questions on several important non-motor aspects of PD. The Task Force recommends
      that the MDS sponsor the development of a new version of the UPDRS and encourage
      efforts to establish its clinimetric properties, especially addressing the need
      to define a Minimal Clinically Relevant Difference and a Minimal Clinically
      Relevant Incremental Difference, as well as testing its correlation with the
      current UPDRS. If developed, the new scale should be culturally unbiased and be
      tested in different racial, gender, and age-groups. Future goals should include
      the definition of UPDRS scores with confidence intervals that correlate with
      clinically pertinent designations, "minimal," "mild," "moderate," and "severe"
      PD. Whereas the presence of non-motor components of PD can be identified with
      screening questions, a new version of the UPDRS should include an official
      appendix that includes other, more detailed, and optionally used scales to
      determine severity of these impairments.

PMID- 12815653
TI  - Clinical features and neuroimaging of PARK7-linked parkinsonism.
AB  - We recently reported linkage to chromosome 1p36 (the PARK7-locus) in a family
      with early-onset parkinsonism. Linkage to this locus has since been confirmed in
      an independent data set. We describe clinical and neuroimaging features of the 4
      patients in the original PARK7-linked kindred. Age at onset of parkinsonism
      varied from 27 to 40 years. Clinical progression was slow, and response to
      dopaminergic therapy good. The clinical spectrum ranged from mild hypokinesia and
      rigidity, to severe parkinsonism with levodopa-induced dyskinesias and motor
      fluctuation. Three of four patients with PARK7-linked parkinsonism exhibited
      psychiatric disturbances. Structural neuroimaging was unremarkable, but
      functional imaging of the brain, carried out in 3 patients, showed significant
      evidence for a presynaptic dopamine deficit, and assessment of cerebral glucose
      metabolism, as carried out in 1 patient, showed possible cerebellar involvement.

PMID- 12815654
TI  - Marked variation in clinical presentation and age of onset in a family with a
      heterozygous parkin mutation.
AB  - Parkin gene mutations have been detected in families with early-onset autosomal
      recessive parkinsonism. We report a novel heterozygous 40 base pair deletion in
      exon 3 of the parkin gene that increases the susceptibility of carriers to
      develop parkinsonism/dystonia and manifests remarkable variability in regard to
      age of onset and phenotype in a single family. After identifying the new mutation
      in the proband of this kindred, family members were contacted and evaluated by a
      movement disorders specialist using standardized protocols and prospectively set
      diagnostic criteria. Importantly, examining physicians and family members were
      blinded to the genetic testing. Five affected members in two generations carried
      the parkin mutation. The proband and one of his brothers had disease onset at 24
      years of age while another brother had disease at age 44. One exhibited multi
      focal dystonia and parkinsonism of 17 years duration, another suffered a
      unilateral slowly progressive parkinsonism over 13 years while the third suffered
      dystonia-parkinsonism of recent onset. A sibling pair in the preceding generation
      had mild previously undiagnosed parkinsonism. Clinicians should be aware that
      patients carrying a parkin gene mutation may present with dystonia-parkinsonism
      or very subtle parkinsonism with a markedly varied age of onset.

PMID- 12815655
TI  - Prevalence of Parkinson's disease and related disorders in the elderly population
      of greater Beijing, China.
AB  - A lower prevalence of Parkinson's disease (PD) has been reported for Chinese
      populations, but it is unclear whether this observation reflects a lower disease
      risk or is an artifact of case finding. We ascertained the prevalence of PD in
      elderly residents of an area that was a composite of 27 urban and rural
      communities of Greater Beijing, China. A team of university neurologists went
      door-to-door throughout the study area, examining 5,743 residents (at age 55
      years or older) and made preliminary determinations of which residents had PD or
      other types of parkinsonism. Final determinations were made after follow-up and
      reevaluation of those persons who were either deemed to have parkinsonism or were
      suspected of having the condition (n = 144; median follow-up = 40 months). Based
      on stringent diagnostic criteria, 110 persons were identified to have
      parkinsonism, of whom 64 (58%) had PD. The prevalence of PD increased with
      advancing age and was about 1% overall and for each gender. In rural communities,
      22 persons had PD, but 20 persons (91%) were first diagnosed for this condition
      by the study neurologists. The prevalence figures obtained in this study are
      similar to some of the highest prevalence figures reported in the West.

PMID- 12815656
TI  - Health status measurement in Parkinson's disease: validity of the PDQ-39 and
      Nottingham Health Profile.
AB  - We assessed the feasibility and psychometric properties of two commonly used
      health status questionnaires in Parkinson's disease (PD): the generic Nottingham
      Health Profile (NHP) and the disease-specific 39-item Parkinson's disease
      Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N =
      81), using traditional and Rasch measurement methodologies. Overall response rate
      was 88%. Both questionnaires were found feasible, although the NHP performed less
      well. The PDQ-39 had fewer floor effects and was better able to separate
      respondents into distinct groups than the NHP, whereas the latter exhibited less
      ambiguous dimensionality and better targeting of respondents with non-extreme
      scores. Reliability and validity indices were similar, and potential differential
      item functioning by age and gender groups was found for both questionnaires. PDQ
      39 response alternatives indicated ambiguity. With few exceptions, questionnaire
      scales were unable to meet recommended standards fully. While preliminary, this
      study illustrates the need for thorough evaluation of outcome measures and has
      implications beyond the questionnaires used here. Although promising, both
      questionnaires warrant further developmental work and stronger support of
      measurement validity before they could be considered fully suitable for valid use
      in PD, in particular in earlier stages of the disease.

PMID- 12815657
TI  - Parkinson's disease is associated with hippocampal atrophy.
AB  - Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with
      controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD
      (patients with PD who have mild cognitive impairment or dementia), Alzheimer's
      disease (AD) and controls using volumetric magnetic resonance imaging (MRI).
      Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control
      subjects) had an informant interview, neurological examination, and psychometric
      testing. Established, reliable methods were used to measure the hippocampus,
      parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction
      for intracranial volume was carried out before comparison. There was no age
      difference between groups (mean age, 74 years). On the Clinical Dementia Rating
      scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and
      AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups.
      Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD,
      1.81. The other volumes did not differ significantly. Among PD and PDD patients,
      recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores
      (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In
      conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD)
      suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging
      might provide an early marker for dementia in PD.

PMID- 12815658
TI  - Locations of movement-related cells in the human subthalamic nucleus in
      Parkinson's disease.
AB  - The subthalamic nucleus (STN) is an emerging target for deep brain stimulator
      (DBS) implantation for the treatment of advanced Parkinson's disease (PD).
      Understanding the somatotopic organization of the STN is important for surgical
      navigation within the nucleus. We analyzed intraoperative data obtained during 54
      procedures for the implantation of STN stimulators to assess the locations of
      movement-related cells. Cells were considered movement-related if they exhibited
      modulation of the cell discharge during passive movement of the contralateral
      upper or lower extremity. Microelectrode track reconstructions were plotted on a
      human brain atlas, using the location of the DBS electrode from postoperative
      magnetic resonance images as a registration mark in reconstructing microelectrode
      track locations. Movement-related cells were predominantly located in the dorsal
      part of the nucleus. The majority of the cells were related to proximal joint
      manipulation. Arm-related cells were located laterally and at the rostral and
      caudal poles, whereas leg-related cells were located medially and centrally. The
      finding of three or more leg-related cells on a given microelectrode track was
      predictive of a medial localization within the motor area. Our findings are
      consistent with the small number of published studies on STN somatopy in the
      human and the nonhuman primate.

PMID- 12815659
TI  - Familial influence on parkinsonism in a rural area of Turkey (Kizilcaboluk
      Denizli): a community-based case-control study.
AB  - This population-based study on parkinsonism in a genetically isolated community
      from a rural area of Turkey aimed to provide a selective evaluation of
      environmental and heritable risk factors. An increased prevalence of parkinsonism
      (4.1%) was detected in the village of Kizilcaboluk for people 65 years of age and
      older. This study included 36 patients with parkinsonism living in Kizilcaboluk
      and three times that number of age- and sex-matched people serving as controls. A
      questionnaire including demographic data, family history, education, occupation,
      data on exposures to pesticides, smoking, alcohol intake, and head trauma was
      administered. We found a significant association of parkinsonism cases with a
      positive family history in first-degree relatives (odds ratio [OR], 7.48; 95%
      confidence interval [CI], 2.52-22.17; P < 0.0001) and with pesticide exposure
      (OR, 2.96; 95% CI, 1.31-6.69; P = 0.015) compared to the control subjects. The
      value of genetically isolated populations for the identification of genetic risk
      factors for common and complex disorders has gained much attention recently
      because the genetic make-up of these populations is likely to be less complex
      than that of the general population and our findings should prompt investigations
      to the nature of a familial aggregation of parkinsonism in this population.

PMID- 12815660
TI  - Lack of effect of polymorphisms in dopamine metabolism related genes on imaging
      of TRODAT-1 in striatum of asymptomatic volunteers and patients with Parkinson's
      disease.
AB  - SPECT scanning using (99)Tc-TRODAT-1, a ligand that binds to dopamine
      transporters, may be useful for detection of early Parkinson's disease (PD),
      diagnosis of presymptomatic individuals, and monitoring disease progression.
      Understanding whether genetic factors contribute to inter-individual variability
      is crucial for interpreting imaging results in the context of disease
      pathophysiology. We tested whether polymorphisms in the genes for catechol-O
      methyltransferase (COMT), monoamine-oxidase B (MAO-B), and the dopamine
      transporter (DAT) influence dopamine uptake parameters in the striatum in vivo in
      asymptomatic volunteers and patients with PD as measured with (99)Tc-TRODAT-1.
      (99)Tc-TRODAT-1 binding declined with age in both asymptomatic volunteers and PD
      patients, and depended on disease duration in PD patients. We found no
      significant association between COMT, MAO-B, and DAT polymorphisms and results of
      (99)Tc-TRODAT-1 testing in asymptomatic volunteers or patients with PD. In PD
      patients, the age of disease onset and speed of progression did not differ based
      on these polymorphisms. These results demonstrate that these specific genetic
      variations do not alter the fidelity of (99)Tc-TRODAT-1 as a measure of
      dopaminergic function in asymptomatic volunteer individuals or patients with PD.

PMID- 12815661
TI  - Visual hallucinations as REM sleep behavior disorders in patients with
      Parkinson's disease.
AB  - To clarify whether visual hallucinations in patients with Parkinson's disease
      (PD) are related to rapid eye movement (REM) sleep, nocturnal polysomnographic
      variables were compared between a group with hallucinations (hallucinators, n =
      14) and a group without hallucinations (nonhallucinators, n = 8). A multiple
      sleep latency test (MSLT) was performed on 3 hallucinators, and the content of
      dreams during daytime REM sleep was investigated. The efficacy of clonazepam, a
      standard treatment choice for REM sleep behavior disorders, was investigated in 8
      hallucinators. Nocturnal polysomnograms of the hallucinators showed a higher
      amount of stage 1-REM sleep with tonic electromyogram (stage 1-REM) than the
      nonhallucinators, and the reported occurrences of nocturnal hallucinations
      corresponded with the periods of stage REM or stage 1-REM in most hallucinators.
      The frequency of sleep onset REM periods (SOREMP) on the MSLT were pathologically
      high in the hallucinators, and the content of the dreams during the MSLT period
      was quite similar to their hallucinations. During clonazepam treatment, the
      frequency of hallucinatory symptoms decreased in 5 of 8 hallucinators. These
      results indicate that visual hallucinations in PD are likely to be related to a
      REM sleep disorder manifested as the appearance of both stage 1-REM during the
      night and SOREMP in the daytime.

PMID- 12815662
TI  - Influence of target size on vertical gaze palsy in a pathologically proven case
      of progressive supranuclear palsy.
AB  - We document a new oculomotor phenomenon in a patient with pathologically proven
      progressive supranuclear gaze palsy (PSP), namely that vertical gaze excursion
      improves with larger pursuit targets. We used computerised video-oculography
      during vertical smooth pursuit eye movements (SPEM) of circular targets of
      diameter 0.16 degrees and 16 degrees, sinusoidally oscillating at 0.08 Hz (peak
      to-peak amplitude 49 degrees). Increasing target size improved vertical gaze
      excursion from 10 degrees to 25 degrees. There was no concomitant increase in
      slow phase eye velocity. The findings could be explained by a potentiation of the
      position control mechanism of pursuit by target size due to increased activation
      of brainstem pursuit-optokinetic pathways and to higher order attentional
      mechanisms. This observation may be useful in the clinical assessment of PSP
      patients with severe neck rigidity in whom the doll's head-eye manoeuvre cannot
      be performed by comparing the degree of vertical gaze palsy during smooth pursuit
      testing between at least two differently sized targets and observing whether
      there is a larger excursion in response to a large target such as a newspaper.

PMID- 12815663
TI  - Essential tremor is not associated with alpha-synuclein gene haplotypes.
AB  - A specific allele of the NACP-Rep1 polymorphism within the alpha-synuclein
      promoter was found to be associated both with Parkinson's disease and essential
      tremor. We repeated the association study on a large series of Italian patients
      with essential tremor using a panel of polymorphisms within the alpha-synuclein
      gene. Our results did not confirm the association reported previously and failed
      to identify a alpha-synuclein specific haplotype as susceptibility factor for
      essential tremor.

PMID- 12815664
TI  - Normal intracortical excitability in developmental stuttering.
AB  - Persistent developmental stuttering (PDS) shares clinical features with task
      specific dystonias. In these dystonias, intracortical inhibition is abnormally
      weak. We therefore sought to determine intracortical inhibition and intracortical
      facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD
      13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated
      resting and active motor thresholds as well as intracortical inhibition and
      facilitation of the optimal representation of the abductor digiti minimi of the
      dominant hand using transcranial magnetic stimulation. In PDS, the resting and
      active motor thresholds were increased, whereas intracortical inhibition and
      facilitation were normal. Normal intracortical excitability makes a
      pathophysiological analogy between focal dystonia and PDS less likely. The
      enhanced motor threshold suggests reduced motor cortical neuronal membrane
      excitability in PDS.

PMID- 12815665
TI  - Coping strategies for visual hallucinations in Parkinson's disease.
AB  - We assessed the use of coping strategies in Parkinson's disease patients with
      visual hallucinations, using a semi-structured questionnaire. We found that 36 of
      our 46 Parkinson's disease subjects with hallucinations (78%) used coping
      strategies: cognitive techniques in 69%; interactive techniques in 62%; and
      visual techniques in 33%.

PMID- 12815666
TI  - An artist's view of drug-induced hallucinosis.
AB  - The occurrence of hallucinations in patients with Parkinson's disease is often
      related to antiparkinsonian therapy, but other factors such as cognitive decline
      and sleep-cycle disturbances are thought to contribute. We describe an artist who
      depicted her visual hallucinations experienced in the course of Parkinson's
      disease.

PMID- 12815667
TI  - Tongue tremor in a patient with coma after electrical injury.
AB  - We report on the case of a patient with transient tongue tremor and coma after
      electrical injury, probably due to a reversible brainstem dysfunction. We then
      reviewed the differential diagnosis of abnormal involuntary movements of the
      tongue as well as movement disorders related to electrocution.

PMID- 12815668
TI  - Episodic focal lingual dystonic spasms.
AB  - We present the clinical history of a woman with idiopathic episodic focal lingual
      dystonic spasms. Although dystonic spasms of the tongue have been reported as a
      primary persistent phenomenon and as a feature of secondary dystonias, primary
      episodic lingual dystonias are rare, tend to be unilateral, and in contrast to
      most other paroxysmal movement disorders, do not appear responsive to anti
      epileptic drugs.

PMID- 12815669
TI  - Chorea as a presenting feature of variant Creutzfeldt-Jakob disease.
AB  - We report on a patient with pathologically proven variant Creutzfeld-Jakob
      disease in whom chorea was a presenting feature of the disease, and was
      unaccompanied by the typical prodrome of psychiatric disturbance or sensory
      symptoms.

PMID- 12815670
TI  - REAL and CALM: what have we learned?

PMID- 12815671
TI  - Centering the projection reconstruction trajectory: reducing gradient delay
      errors.
AB  - The projection reconstruction (PR) trajectory was investigated for the effect of
      gradient timing delays between the actual and requested start time of each
      physical gradient. Radial trajectories constructed with delayed gradients miss
      the center of k-space in an angularly dependent manner, causing effective echo
      times to vary with projection angle. The gradient timing delays were measured in
      phantoms, revealing delays on the x, y, and z gradients which differed by as much
      as 5 micro sec. Using this one-time calibration measurement, the trajectories
      were corrected for gradient delays by addition of compensatory gradient areas to
      the prephasers of the logical x and y readout gradients. Effective projection-to
      projection echo time variability was reduced to less than 1 micro sec for all
      imaging orientations. Using corrected trajectories, artifacts were reduced in
      phantom images and in volunteer studies. This correction should potentiate
      greater clinical use of the PR trajectory.

PMID- 12815672
TI  - Detection of the anoxic depolarization of focal ischemia using manganese-enhanced
      MRI.
AB  - Mismatch between diffusion- and perfusion-weighted MRI was used to indicate a
      treatable area following focal ischemia, called the penumbra. Activity-induced
      manganese contrast MRI has been reported as a new visualization method for neural
      activation using manganese ions as a depolarization-dependent contrast agent. It
      is well known that energy failure induced by cerebral ischemia produces anoxic
      depolarization. The purpose of this study was to detect manganese accumulation
      caused by permanent middle cerebral artery occlusion (MCAO) of rat brain and to
      compare regional differences between manganese accumulation and decreased
      apparent diffusion coefficient (ADC). The ratios of signal intensity of manganese
      enhanced MRI in the ipsilateral cortex to that in the contralateral cortex were
      171.0 +/- 17.5% in MCAO group and 108.4 +/- 13.2% in the sham group. In addition,
      the enhanced region was much smaller than the area which was detected as having a
      reduced ADC.

PMID- 12815673
TI  - Modified perturbation method for transverse electromagnetic (TEM) coil tuning and
      evaluation.
AB  - A modified perturbation method for tuning and testing volume head coils was
      developed. The common perturbation method, utilizing the change in resonance
      frequency of a resonator in response to the presence of a small dielectric or
      magnetic probe, was modified to modulate the frequency shift due to rotation of a
      probe. This modification enabled the RF magnetic and electric fields as well as
      the angular distribution of current in the longitudinal elements of the coil to
      be mapped. The latter serves as a quick test of magnetic field homogeneity by
      comparing the measured distribution with the sinusoidal function required for the
      field to be homogenous. The method was experimentally applied to tune and test a
      transverse electromagnetic (TEM) head coil.

PMID- 12815674
TI  - Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of
      difference-edited spectra.
AB  - The concentration of reduced glutathione (GSH), an antioxidant, may be altered in
      various brain diseases. MEGA-PRESS was used to edit for the (1)H NMR signal from
      GSH in the occipital lobe of 12 normal humans. In all studies, GSH was clearly
      detected with a spectral pattern consistent with spectra acquired from a phantom
      containing GSH. Retention of singlet resonances in the subspectra, a key
      advantage of this difference-editing technique, provided an unambiguous reference
      for the offset and phase of the edited signal. Linear combination model (LCModel)
      analysis provided an unbiased means for quantifying signal contribution from
      edited metabolites. GSH concentration was estimated from the in vivo spectra as
      1.3 +/- 0.2 micro mol/g (mean +/- SD, n = 12).

PMID- 12815675
TI  - Developmental and regional changes in the neurochemical profile of the rat brain
      determined by in vivo 1H NMR spectroscopy.
AB  - Sixteen metabolites were quantified from 11-24 micro l volumes in three different
      brain regions (hippocampus, striatum, and cerebral cortex) during postnatal
      development. Rat pups from the same litter were repeatedly measured on postnatal
      days 7, 10, 14, 21, and 28 using a completely noninvasive and longitudinal study
      design. Metabolite quantification was based on ultra-short echo-time (1)H NMR
      spectroscopy at 9.4 T and LCModel processing. Most of the brain metabolites were
      quantified with Cramer-Rao lower bounds (CRLB) less than 20%, which corresponded
      to an estimated concentration error <0.2 micro mol/g. Taurine and total creatine
      were quantified with CRLB < or = 5% from all 114 processed spectra. The resulting
      high reliability and reproducibility revealed significant regional and age
      related changes in metabolite concentrations. The most sensitive markers for
      developmental and regional variations between hippocampus, striatum, and cerebral
      cortex were N-acetylaspartate, myo-inositol, taurine, glutamate, and choline
      compounds. Absolute values of metabolite concentrations were in very good
      agreement with previously published in vitro results based on chromatographic
      measurements of brain extracts. The current data may serve as a reference for
      studies focused on developmental defects and pathologies using neonatal rat
      models.

PMID- 12815676
TI  - In vivo trans-synaptic tract tracing from the murine striatum and amygdala
      utilizing manganese enhanced MRI (MEMRI).
AB  - Small focal injections of manganese ion (Mn(2+)) deep within the mouse central
      nervous system combined with in vivo high-resolution MRI delineate neuronal
      tracts originating from the site of injection. Previous work has shown that
      Mn(2+) can be taken up through voltage-gated Ca(2+) channels, transported along
      axons, and across synapses. Moreover, Mn(2+) is a paramagnetic MRI contrast
      agent, causing positive contrast enhancement in tissues where it has accumulated.
      These combined properties allow for its use as an effective MRI detectable
      neuronal tract tracer. Injections of low concentrations of MnCl(2) into either
      the striatum or amygdala produced significant contrast enhancement along the
      known neuronal circuitry. The observed enhancement pattern is different at each
      injection site and enhancement of the homotopic areas was observed in both cases.
      Ten days postinjection, the Mn(2+) had washed out, as evidenced by the absence of
      positive contrast enhancement within the brain. This methodology allows imaging
      of neuronal tracts long after the injection of the ion because Mn(2+)
      concentrates in active neurons and resides for extended periods of time. With
      appropriate controls, differentiation of subsets of neuronal pathways associated
      with behavioral and pharmacological paradigms should be feasible.

PMID- 12815677
TI  - MRI detection of weak magnetic fields due to an extended current dipole in a
      conducting sphere: a model for direct detection of neuronal currents in the
      brain.
AB  - To investigate the feasibility of direct MR detection of neuronal activity in the
      brain, neuronal current flow was modeled as an extended current dipole located in
      a conducting sphere. The spatially varying magnetic field induced within the
      sphere by such a dipole was calculated, including its form close to and within
      the current source. The predicted field variation was experimentally verified by
      measurements of the variation in phase of the MR signal in a sphere containing a
      model dipole. The effects of the calculated magnetic field distributions on the
      phase and magnitude of the signal in MR images were explored. The minimum
      detectable dipole strength under normal experimental conditions was calculated to
      be about 4.5 nAm, which is similar in magnitude to dipole strengths from evoked
      neuronal activity, and is an order of magnitude smaller than dipole strengths
      expected from spontaneous activity. This minimum detectable dipole strength
      increases with increasing spatial extent of the primary current distribution. In
      the experimental work, the effects of a field of [1.1 +/- 0.5] x 10(-10) T
      strength were detected, corresponding to the maximum net field caused by a dipole
      of 6.3 nAm strength with a spatial extent of 3 x 3 x 2 mm(3).

PMID- 12815678
TI  - Peripheral nerve stimulation properties of head and body gradient coils of
      various sizes.
AB  - Peripheral nerve stimulation (PNS) caused by time-varying magnetic fields has
      been studied both theoretically and experimentally. A human volunteer study
      performed on three different body-size gradient coils and one head-size gradient
      coil is presented in this work. The experimental results were used to generate
      average PNS threshold parameters for the tested gradient systems. It was found
      that the average stimulation threshold increases while gradient-region-of
      uniformity size decreases. In addition, linear relationships between PNS
      parameters and diameter of homogeneous gradient spherical volume (DSV) were
      discovered: SR(min) and DeltaG(min) both vary inverse linearly with DSV. More
      importantly, the chronaxie value was found to vary inversely linearly with the
      DSV. This finding indicates that, contrary to the general understanding, the
      parameter "chronaxie" in the commonly accepted simple stimulation models cannot
      be considered to be a single-value, nerve-specific constant. A modified linear
      model for gradient-induced PNS based on these results was developed, which may
      permit, for the first time, the general prediction of nerve stimulation
      properties for gradient coils of arbitrary linear region dimension.

PMID- 12815679
TI  - Density of organic matrix of native mineralized bone measured by water- and fat
      suppressed proton projection MRI.
AB  - Water- and fat-suppressed projection MR imaging (WASPI) utilizes the large
      difference between the proton T(2) (*)s of the solid organic matrix and the fluid
      constituents of bone to suppress the fluid signals while preserving solid matrix
      signals. The solid constituents include collagen and some molecularly immobile
      water and exhibit very short T(2) (*). The fluid constituents include mobile
      water and fat, with long T(2) (*). In WASPI, chemical shift selective low-power
      pi/2 pulses excite mobile water and fat magnetization which is subsequently
      dephased by gradient pulses, while the magnetization of collagen and immobile
      water remains mostly in the z-direction. Additional selective pi pulses in
      alternate scans further cancel the residual water and fat magnetization.
      Following water and fat suppression, the matrix signal is excited by a short hard
      pulse and the free induction decay acquired in the presence of a gradient in a 3D
      projection method. WASPI was implemented on a 4.7 T MR imaging system and tested
      on phantoms and bone specimens, enabling excellent visualization of bone matrix.
      The bone matrix signal per unit volume of bovine trabecular specimens was
      measured by this MR technique and compared with that determined by chemical
      analysis. This method could be used in combination with bone mineral density
      measurement by solid state (31)P projection MRI to determine the degree of bone
      mineralization.

PMID- 12815680
TI  - High-resolution MRI with cardiac and respiratory gating allows for accurate in
      vivo atherosclerotic plaque visualization in the murine aortic arch.
AB  - Genetically engineered mouse models provide enormous potential for investigation
      of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging
      methods for analysis of atherosclerosis in mice are currently limited. This study
      aimed to demonstrate the feasibility of MRI to noninvasively visualize
      atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein
      E, who develop atherosclerotic lesions similar to those observed in humans. To
      freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)
      weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial
      image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of
      the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI
      with corresponding cross-sectional histopathology showed excellent agreement of
      aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new
      insights into the mechanisms involved in progression and regression of
      atherosclerotic disease.

PMID- 12815681
TI  - Accuracy and uniqueness of three in vivo measurements of atherosclerotic carotid
      plaque morphology with black blood MRI.
AB  - High-resolution MRI provides unique information about morphology of
      atherosclerotic carotid plaque. In this study, the accuracy and precision of
      measurements of carotid plaque burden and lumen narrowing were determined for in
      vivo black blood MRI assessment with respect to ex vivo MRI in a group of 37
      atherosclerosis patients who underwent carotid endarterectomy (CEA). Three
      different plaque measures were compared between paired in vivo and ex vivo MR
      images: maximum wall area (MWA), minimum lumen area (mLA), and wall volume (WV).
      MWA and WV are measures of plaque burden, while mLA is a measure of lumen
      narrowing. The matched in vivo and ex vivo measurements showed good agreement
      (the correlation coefficients for in/ex vivo WV, MWA, and mLA were 0.92, 0.91,
      0.90, respectively) with predictable bias. This study indicates that in vivo
      black blood MRI can be used to directly estimate the morphology of the plaque.
      Comparison of the three plaque measures showed that mLA and MWA or WV provide
      different information regarding the atherosclerotic lesions (the correlation
      coefficients between mLA and MWA or WV were less than 0.3). Black blood MRI
      technique is a potentially powerful clinical tool to characterize the severity of
      atherosclerotic plaque. It can provide accurate measurements on different aspects
      of the plaque, from plaque burden to lumen narrowing.

PMID- 12815682
TI  - Quantitative magnetization transfer mapping of bound protons in multiple
      sclerosis.
AB  - Quantitative analysis of magnetization transfer images has the potential to allow
      a more thorough characterization of the protons, both bound and free, in a tissue
      by extracting a number of parameters relating to the NMR properties of the
      protons and their local environment. This work develops previously presented
      techniques to produce estimates of parameters such as the bound proton fraction,
      f, and the transverse relaxation time of the bound pool, T(2B), for the whole
      brain in a clinically acceptable imaging time. This is achieved by limiting the
      number of data collected (typically to 10); to collect 28 5-mm slices with a
      reconstructed resolution of 0.94 x 0.94 mm. The protocol takes 82 sec per data
      point. The fitting technique is assessed against previous work and for fitting
      failures. Maps and analysis are presented from a group of seven controls and 20
      multiple sclerosis patients. The maps show that the parameters are sensitive to
      tissue-specific differences and can detect pathological change within lesions.
      Statistically significant differences in parameters such as T(2B) and f are seen
      between normal-appearing white matter, multiple sclerosis lesions, and control
      white matter. Whole-brain histograms of these parameters are also presented,
      showing differences between patients and controls.

PMID- 12815683
TI  - Textural analysis of contrast-enhanced MR images of the breast.
AB  - Texture analysis was applied to high-resolution, contrast-enhanced (CE) images of
      the breast to provide a method of lesion discrimination. Significant differences
      were seen between benign and malignant lesions for a number of textural features,
      including entropy and sum entropy. Using logistic regression analysis (LRA), a
      diagnostic accuracy of A(z) = 0.80 +/- 0.07 was obtained with a model requiring
      only three parameters. By initially dividing the patient data into training and
      test datasets, reasonable model robustness was also established. On combining
      features obtained using textural analysis with lesion size, time to maximum
      enhancement, and patient age, a diagnostic accuracy of A(z) = 0.92 +/- 0.05 was
      demonstrated.

PMID- 12815684
TI  - Measuring the effects of indomethacin on changes in cerebral oxidative metabolism
      and cerebral blood flow during sensorimotor activation.
AB  - The work presented here uses combined blood oxygenation level-dependent (BOLD)
      and arterial spin tagging (AST) approaches to study the effect of indomethacin on
      cerebral blood flow (CBF) and oxygen consumption (CMRO(2)) increases during motor
      activation. While indomethacin reduced the CBF increase during activation, it did
      not significantly affect the CMRO(2) increase during activation. The ratio of the
      activation-induced CBF increase in the presence and absence of indomethacin was
      0.54 +/- 0.08 (+/-SEM, n = 8, P < 0.001), while the ratio of the CMRO(2) increase
      in the presence and absence of the drug was 1.02 +/- 0.08 (+/-SEM, N = 8, ns).
      Potential difficulties in estimating CMRO(2) changes from combined BOLD/AST data
      are discussed.

PMID- 12815685
TI  - Combined diffusion and strain MRI reveals structure and function of human
      myocardial laminar sheets in vivo.
AB  - The mechanism of ventricular thickening in normal humans was investigated using
      in vivo MRI. The hypothesis that myocardial laminar sheets contribute to
      ventricular thickening predominantly via sheet shear and sheet extension, as
      previously found invasively in canine studies at particular ventricular sites,
      was tested. In normal human subjects, registered images of myocardial sheet
      architecture and strain at the mid-left ventricle (mid-LV) at mid-systole were
      acquired with diffusion and strain MRI. Sheet function was analyzed by computing
      myocardial strain in the local fiber-sheet coordinates. In general, myocardial
      sheets contribute to ventricular thickening through all three cross-fiber strain
      components: sheet shear, sheet extension, and sheet-normal thickening (previously
      undocumented). Each of these components demonstrated substantial spatial
      heterogeneity, with sheet shear and sheet extension usually predominant in the
      anterior free wall, and sheet-normal thickening predominant near the right
      ventricular (RV) insertions. However, considerable intersubject variability was
      also found. In all cases, the contributions to thickening of fiber strains were
      small. Sheet function in normal humans was found to be heterogeneous and
      variable, contrasting with the uniform and symmetric ventricular patterns of
      fiber shortening and wall thickening. The study demonstrates that noninvasive NMR
      imaging is a promising tool for investigations of myocardial sheet architecture
      and function, and is particularly suited to the evident complexity of this field
      of study.

PMID- 12815686
TI  - Reduction of RF power for magnetization transfer with optimized application of RF
      pulses in k-space.
AB  - More efficient use of RF power for RF-intensive applications such as
      magnetization transfer (MT) is necessary at high field strength (3.0 T or
      greater) to keep the specific absorption rate (SAR) within regulatory limits. It
      has been demonstrated that RF power deposition can be reduced with minimal impact
      on image quality by preferential application of MT pulses to the central phase
      encoding views. This work extends that approach to both phase-encoding directions
      in a 3D acquisition (i.e., phase and slice) and further improves it by modulating
      the flip angle of the MT pulse according to the phase-encoded view's distance to
      the center of k-space. This technique is implemented for 3D time-of-flight (TOF)
      MR angiography (MRA) and the parameters for MT pulse are optimized based on
      phantom studies at 3.0 T. MT applied with this method at 3.0 T is shown to
      improve the blood vessel detectability in high-resolution intracranial 3D TOF MRA
      exams of 11 patients.

PMID- 12815687
TI  - Novel prospective respiratory motion correction approach for free-breathing
      coronary MR angiography using a patient-adapted affine motion model.
AB  - A novel technique is presented which enables the calibration of a 3D affine
      respiratory motion model to the individual motion pattern of the patient. The
      concept of multiple navigators and precursory navigators is introduced to address
      nonlinear properties and hysteresis effects of the model parameters with respect
      to the conventional diaphragmatic navigator. The optimal combination and
      weighting of the navigators is determined on the basis of a principal component
      analysis (PCA). Thus, based on a given navigator measurement the current motion
      state of the object can be predicted by means of the calibrated motion model. The
      3D motion model is applied in high-resolution coronary MR angiography
      examinations (CMRA) to prospectively correct for respiration-induced motion. The
      basic feasibility of the proposed calibration procedure was shown in 16
      volunteers. Furthermore, the application of the calibrated motion model for CMRA
      examinations of the right coronary artery (RCA) was tested in 10 volunteers. The
      superiority of a calibrated 3D translation model over the conventional 1D
      translation model with a fixed correction factor and the potential of affine
      prospective motion correction for CMRA are demonstrated.

PMID- 12815688
TI  - Three-dimensional BOLD fMRI with spin-echo characteristics using T2 magnetization
      preparation and echo-planar readouts.
AB  - A new approach to mixed T(2)- and T(2) (*)-weighted BOLD fMRI is presented, which
      combines T(2) magnetization preparation (T2prep) with a series of EPI readouts.
      This technique allows full 3D, time-efficient imaging to be performed with low RF
      power deposition. Steady-state calculations are performed in order to study
      signal formation in 3D T2prep-EPI sequences. Results obtained under the
      hypothesis of ideal spoiling are compared to full Bloch equation solutions. The
      theoretical findings are validated by means of in vitro and in vivo signal
      measurements. Several variants of the 3D T2prep-EPI approach are shown to be
      usable for visual cortex fMRI and compared to conventional 3D coherent gradient
      echo EPI. The relative sensitivity of these sequences is shown to be predictable
      by means of a simple DeltaT(2)/DeltaT(2) (*) model.

PMID- 12815689
TI  - Evaluation of systematic quantification errors in velocity-selective arterial
      spin labeling of the brain.
AB  - Velocity-selective (VS) sequences potentially permit arterial spin labeling (ASL)
      perfusion imaging with labeling applied very close to the tissue. In this study
      the effects of cerebrospinal fluid (CSF) motion, radiofrequency (RF) field
      imperfections, and sequence timing parameters on the appearance and quantitative
      perfusion values obtained with VS-ASL were evaluated. Large artifacts related to
      CSF motion were observed with moderate velocity weighting, which were removed by
      inversion recovery preparation at the cost of increased imaging time. Imperfect
      refocusing and excitation pulses resulting from nonuniform RF fields produced
      systematic errors in the ASL subtraction images. A phase cycling scheme was
      introduced to eliminate these errors. Quantitative perfusion images were obtained
      with CSF suppression and phase cycling. Gray matter blood flow of 27.7 ml 100 g(
      1) min(-1), approximately half the value reported in studies using spatially
      selective ASL, was measured. Potential sources for this underestimation are
      discussed.

PMID- 12815690
TI  - Real-time imaging of two-dimensional cardiac strain using a harmonic phase
      magnetic resonance imaging (HARP-MRI) pulse sequence.
AB  - The harmonic phase (HARP) method provides automatic and rapid analysis of tagged
      magnetic resonance (MR) images for quantification and visualization of myocardial
      strain. In this article, the development and implementation of a pulse sequence
      that acquires HARP images in real time are described. In this pulse sequence, a
      CINE sequence of images with 1-1 spatial modulation of magnetization (SPAMM) tags
      are acquired during each cardiac cycle, alternating between vertical and
      horizontal tags in successive heartbeats. An incrementing train of imaging RF
      flip angles is used to compensate for the decay of the harmonic peaks due to both
      T(1) relaxation and the applied imaging pulses. The magnitude images displaying
      coarse anatomy are automatically reconstructed and displayed in real time after
      each heartbeat. HARP strain images are generated offline at a rate of four images
      per second; real-time processing should be possible with faster algorithms or
      computers. A comparison of myocardial contractility in non-breath-hold and breath
      hold experiments in normal humans is presented.

PMID- 12815691
TI  - Tracer arrival timing-insensitive technique for estimating flow in MR perfusion
      weighted imaging using singular value decomposition with a block-circulant
      deconvolution matrix.
AB  - Relative cerebral blood flow (CBF) and tissue mean transit time (MTT) estimates
      from bolus-tracking MR perfusion-weighted imaging (PWI) have been shown to be
      sensitive to delay and dispersion when using singular value decomposition (SVD)
      with a single measured arterial input function. This study proposes a technique
      that is made time-shift insensitive by the use of a block-circulant matrix for
      deconvolution with (oSVD) and without (cSVD) minimization of oscillation of the
      derived residue function. The performances of these methods are compared with
      standard SVD (sSVD) in both numerical simulations and in clinically acquired
      data. An additional index of disturbed hemodynamics (oDelay) is proposed that
      represents the tracer arrival time difference between the AIF and tissue signal.
      Results show that PWI estimates from sSVD are weighted by tracer arrival time
      differences, while those from oSVD and cSVD are not. oSVD also provides estimates
      that are less sensitive to blood volume compared to cSVD. Using PWI data that can
      be routinely collected clinically, oSVD shows promise in providing tracer arrival
      timing-insensitive flow estimates and hence a more specific indicator of ischemic
      injury. Shift maps can continue to provide a sensitive reflection of disturbed
      hemodynamics.

PMID- 12815692
TI  - Spatial normalization of diffusion tensor fields.
AB  - A method for the spatial normalization and reorientation of diffusion tensor (DT)
      fields is presented. Spatial normalization of tensor fields requires an
      appropriate reorientation of the tensor on each voxel, in addition to its
      relocation into the standardized space. This appropriate tensor reorientation is
      determined from the spatial normalization transformation and from an estimate of
      the underlying fiber direction. The latter is obtained by treating the principal
      eigenvectors of the tensor field around each voxel as random samples drawn from
      the probability distribution that represents the direction of the underlying
      fiber. This approach was applied to DT images from nine normal volunteers, and
      the results show a significant improvement in signal-to-noise ratio (SNR) after
      spatial normalization and averaging of tensor fields across individuals. The
      statistics of the spatially normalized tensor field, which represents the tensor
      characteristics of normal individuals, may be useful for quantitatively
      characterizing individual variations of white matter structures revealed by DT
      imaging (DTI) and deviations caused by pathology. Simulated experiments using
      this methodology are also described.

PMID- 12815693
TI  - Super-parallel MR microscope.
AB  - A super-parallel MR microscope in which multiple (up to 100) samples can be
      imaged simultaneously at high spatial resolution is described. The system
      consists of a multichannel transmitter-receiver system and a gradient probe array
      housed in a large-bore magnet. An eight-channel MR microscope was constructed for
      verification of the system concept, and a four-channel MR microscope was
      constructed for a practical application. Eight chemically fixed mouse fetuses
      were simultaneously imaged at the 200 micro m(3) voxel resolution in a 1.5 T
      superconducting magnet of a whole-body MRI, and four chemically fixed human
      embryos were simultaneously imaged at 120 micro m(3) voxel resolution in a 2.35 T
      superconducting magnet. Although the spatial resolutions achieved were not
      strictly those of MR microscopy, the system design proposed here can be used to
      attain a much higher spatial resolution imaging of multiple samples, because
      higher magnetic field gradients can be generated at multiple positions in a
      homogeneous magnetic field.

PMID- 12815694
TI  - Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple
      sclerosis.
AB  - It is well known that multiple sclerosis (MS) pathogenesis continues even during
      periods of clinical silence. To quantify the metabolic characteristics of this
      activity we compared the absolute levels of N-acetylaspartate (NAA), creatine
      (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between
      relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were
      obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of
      interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched
      controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained
      from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0
      cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40
      +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho
      level was the only single metric differentiating patients from controls at 100%
      specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect
      widespread microscopic inflammation, gliosis, or de- and remyelination in the
      NAWM. Both metabolites are potential prognostic indicators of current disease
      activity, preceding NAA decline and atrophy.

PMID- 12815695
TI  - Parallel spectroscopic imaging with spin-echo trains.
AB  - A reduction in scan time in spectroscopic imaging (SI) can be achieved by both
      fast and reduced k-space sampling. This work presents an ultrafast SI technique
      that combines the two approaches. The synergy of multiple spin-echo (MSE)
      acquisition and sensitivity encoding (SENSE) enables high-resolution SI to be
      performed within a clinically acceptable scan time. MSE-SENSE-SI with echo train
      lengths ranging from one to four echoes is evaluated with respect to SNR and
      spatial response function by means of in vitro experiments. It is shown that
      acquiring two spin-echoes (SEs) per acquisition yields a good practical trade-off
      among scan time, SNR, and spatial response. The clinical feasibility of the
      technique is demonstrated in a patient with an astrocytoma, and SI data are
      obtained with an image matrix of 24 x 24 in just over 2 min.

PMID- 12815696
TI  - MR microscopy of magnetically labeled neurospheres transplanted into the Lewis
      EAE rat brain.
AB  - Stem cell transplantation is being explored as a new paradigm for the treatment
      of demyelinating diseases. Magnetically labeled multipotential neural precursor
      cells were transplanted into the ventricles of rats with acute experimental
      allergic encephalomyelitis (EAE) and high-resolution (microscopic) MR images were
      obtained ex vivo. Migration patterns of live cells into periventricular white
      matter structures could be easily visualized, with a good correlation of the
      corresponding histopathology. The present results confirm that MR cell tracking
      can be used to guide the development of successful transplantation protocols.

PMID- 12815697
TI  - Robust myelin water quantification: averaging vs. spatial filtering.
AB  - The myelin water fraction is calculated, voxel-by-voxel, by fitting decay curves
      from a multi-echo data acquisition. Curve-fitting algorithms require a high
      signal-to-noise ratio to separate T(2) components in the T(2) distribution. This
      work compared the effect of averaging, during acquisition, to data postprocessed
      with a noise reduction filter. Forty regions, from five volunteers, were
      analyzed. A consistent decrease in the myelin water fraction variability with no
      bias in the mean was found for all 40 regions. Images of the myelin water
      fraction of white matter were more contiguous and had fewer "holes" than images
      of myelin water fractions from unfiltered echoes. Spatial filtering was effective
      for decreasing the variability in myelin water fraction calculated from 4-average
      multi-echo data.

PMID- 12815698
TI  - Fat-suppressed steady-state free precession imaging using phase detection.
AB  - Fully refocused steady-state free precession (SSFP) is a rapid, efficient imaging
      sequence that can provide diagnostically useful image contrast. In SSFP, the
      signal is refocused midway between excitation pulses, much like in a spin-echo
      experiment. However, in SSFP, the phase of the refocused spins alternates for
      each resonant frequency interval equal to the reciprocal of the sequence
      repetition time (TR). Appropriate selection of the TR results in a 180 degrees
      phase difference between lipid and water signals. This phase difference can be
      used for fat-water separation in SSFP without any increase in scan time. The
      technique is shown to produce excellent non-contrast-enhanced, flow-independent
      angiograms of the peripheral vasculature.

PMID- 12815699
TI  - Simple analytic variable density spiral design.
AB  - Variable density spirals have been proposed in a variety of applications,
      including MR fluoroscopy, cardiac imaging, and MR spectroscopic imaging. In this
      work, a simple analytic solution for designing a flexible set of variable density
      spiral trajectory waveforms is presented. The method enables real-time waveform
      prescription on scanners with limited computational power. Both slew rate-limited
      and amplitude-limited regimes are incorporated in the design process.

PMID- 12815700
TI  - Electromagnetic actuator for generating variably oriented shear waves in MR
      elastography.
AB  - Magnetic resonance elastography (MRE) is a recently developed technique for
      determining the mechanical properties of biological tissue. In dynamic MRE,
      electromagnetic units (actuators) are widely used to generate shear waves in
      tissue. These actuators exploit the interaction between the static magnetic field
      B(0) and an annular coil supplied with alternating currents. Therefore, coil
      movements are restricted to selected orientations to B(0). Conventional actuators
      transfer this movement collinearly to B(0) into the tissue. In this study, an
      electromagnetic actuator was introduced that overcomes this limitation. It is
      demonstrated that different directions of mechanical excitation can be generated
      and monitored by MRE. Different spatial components of the propagation of the
      shear waves were determined using agarose phantoms. The technique allows maximum
      contrast for MRE images of objects with anisotropic strain components such as
      muscle tissue.

PMID- 12815701
TI  - Control characteristics of an automatic matching control system for in vivo EPR
      spectroscopy.
AB  - A method for estimating the characteristics of an automatic matching control
      (AMC) system for in vivo electron paramagnetic resonance (EPR) spectroscopy is
      described. AMC is also known as automatic coupling control (ACC) and is used to
      compensate for perturbation due to movement of the subject animal. The open-loop
      function of the AMC system is derived and the characteristics (gain, phase
      margin, steady-state error, system bandwidth, and disturbance rejection) of the
      system are examined. The proposed method is supported by experimental findings.
      The frequency response of perturbation due to the movement of an anesthetized rat
      was measured with a 1.1-GHz continuous-wave EPR spectrometer. Disturbance
      rejection with the AMC system was also considered for respiratory motion and the
      heartbeat of the anesthetized rat, and these perturbations were reduced by about
      40 dB in the power spectrum of the output of the diode detector in the
      spectrometer.

PMID- 12815703
TI  - Insulin-like growth factor 1 is essential for normal dendritic growth.
AB  - This study evaluated somatic and dendritic growth of neurons in the
      frontoparietal cortex of Igf1-/- brains. Pyramidal neuron density was increased
      by approximately 25% (P =.005) and soma size reduced by approximately 10% (P
      <.001). Golgi staining revealed that cortical layer II-III neurons exhibited a
      significant reduction in dendritic length and complexity in Igf1 null mice.
      Dendritic spine density and presumably synaptic contacts were reduced by 16% (P
      =.002). Similar findings were obtained for cortical layer V and piriform cortex
      pyramids. Supporting a reduction in synapses, synaptotagmin levels were reduced
      by 30% (P <.02) in the Igf1 null brain. Investigation of factors critically
      involved in dendritic growth and synaptogenesis showed an approximately 50%
      reduction in cortical CDC42 protein expression (P <.001) and an approximately 10%
      reduction in brain cholesterol levels (P <.01) in Igf1 null mice. Evidence is
      presented that Igf1 deletion causes disruptions in lipid and microtubule
      metabolism, leading to impaired neuronal somatic and dendritic growth. Published
      2003 Wiley-Liss, Inc.

PMID- 12815704
TI  - Role and expression of thrombin receptor PAR-1 in muscle cells and neuromuscular
      junctions during the synapse elimination period in the neonatal rat.
AB  - A role for thrombin and its receptor (ThR) during mammalian skeletal muscle cell
      differentiation and neuromuscular junction (NMJ) formation has been suggested.
      Previously, we found that the synapse elimination process in the neonatal rat
      muscle was accelerated by thrombin and blocked by hirudin, its specific inhibitor
      (Lanuza et al. [2001] J. Neurosci. Res. 63:330-340). To test whether this process
      resulted from a signal transduction cascade initiated by activation of ThR, in
      particular PAR-1, we applied to the levator auris longus (LAL) muscle of newborn
      rats two synthetic peptides (SFLL and FSLL). SFLL is a potent specific agonist
      for activation of PAR-1, whereas FSLL is an inactive peptide. We have
      demonstrated that the activation of PAR-1 by SFLL produced acceleration of the
      presynaptic loss of connections and the postsynaptic maturation of NMJs.
      Moreover, Western blot analysis showed that PAR-1 was present in the skeletal
      muscle, and by immunohistochemistry we detected PAR-1 in muscle fibers
      concentrated in the synaptic area but also in satellite cells. Several lines of
      evidence suggested that PAR-1 is localized in the postsynaptic membrane: PAR-1
      immunofluorescence was concentrated at denervated synaptic sites and was present
      in the myotube membrane in vitro in the absence of neurons and in dissociated
      single muscle fibers from which nerve terminals and Schwann cells had been
      removed. Taken together, these results indicate that thrombin mediates certain
      stages of activity-dependent synapse elimination in the skeletal muscle and does
      so through its action on the thrombin receptor PAR-1 localized, at least in part,
      on the postsynaptic membrane.

PMID- 12815705
TI  - Two populations of microglial cells isolated from rat primary mixed glial
      cultures.
AB  - Because of variations in the morphology and function of microglial cells, it has
      often been claimed that microglial cells should be classified into two or more
      subtypes. However, such subtypes have not fully been characterized. In the
      present study, we isolated microglial cells expressing microglia-markers CD11b
      and CD68 from rat mixed glial cultures on the fifth and on the thirteenth days in
      vitro (DIV 5 and 13) and demonstrate that these two populations of microglial
      cells have distinct morphology and function. Microglial cells isolated on DIV 5,
      which we have termed immature cells, are characterized by the presence of large
      somata, large peroxidase- and alkaline phosphatase-positive granules, and high
      proliferative activity and suppressed responsiveness to lipopolysaccharide (LPS).
      In contrast, the microglial cells isolated on DIV 13, which we have termed mature
      cells, are devoid of granules, appear to be in a state of cell cycle arrest, and
      respond to LPS by the induction of inducible nitric oxide synthase (iNOS), tumor
      necrosis factor-alpha, and interleukin-6. Isolated immature cells maintained in
      pure culture failed to express iNOS in response to LPS. However, if these cells
      were cultured on astrocyte-derived extracellular matrix (AsECM) or pure laminin,
      the cells exhibited an induction of iNOS in response to LPS. AsECM and laminin
      were also able to induce a state of cell cycle arrest in cultured isolated
      immature cells. Thus, classification into two types of microglial cells is
      possible, but both types are in the same cell lineage, because the immature cells
      can differentiate into mature microglial cells in the presence of laminin or
      AsECM. Therefore, "microglioblasts" may be the appropriate term for the immature
      cells.

PMID- 12815706
TI  - Regulation of CNS glial phenotypes in N20.1 cells.
AB  - The N20.1 oligodendroglial cell line, immortalized with SV40 T antigen,
      simultaneously expresses oligodendroglial markers and glial fibrillary acidic
      protein (GFAP), an astroglial marker. This study examines the plasticity of N20.1
      cells with regard to GFAP expression, and its relationship to expression of SV40
      T antigen, p53, and a novel nuclear antigen detected by the A007 monoclonal
      antibody. Marked changes occur in GFAP levels and cell morphology when N20.1
      cells are switched from the permissive temperature (34 degrees C) to the non
      permissive temperature (39 degrees C), and with cyclic AMP elevation at 39
      degrees C. At 34 degrees C, levels of GFAP are high; when cells are switched to
      39 degrees C, GFAP levels decrease significantly, then increase slightly when
      forskolin is added. At both temperatures, the cells display feathery GFAP
      immunostaining. When forskolin is added at 39 degrees C, however, cells display
      bright fibrous GFAP staining in elongated processes. The changes in GFAP were
      compared to changes in T antigen and p53. As expected, the decrease in T antigen
      at 39 degrees C was accompanied by movement of p53 from the nucleus to cytoplasm.
      Total p53 levels did not change, however, and forskolin did not alter the
      respective distribution or levels of p53 at either temperature. At both
      temperatures, the cell bodies and processes show internal expression of
      sulfatide, as demonstrated with the O4, Sulph I, and A007 antibodies. We show,
      for the first time, abundant nuclear immunoreactivity with the A007 monoclonal
      antibody in the N20.1 cells. This nuclear reactivity is seen at 34 degrees C, but
      not at 39 degrees C, similar to p53, and is not detected with the other sulfatide
      antibodies. Double-label immunostaining shows that the nuclear A007
      immunoreactivity is co-localized in nuclear structures with T antigen and p53 at
      34 degrees C, but is not found in every nucleus containing these antigens. We
      conclude that regulation of GFAP expression and morphology in N20.1 cells is
      dependent on a combination of T antigen expression and level of cAMP and may be
      related to regulation of p53 and the A007 nuclear antigen.

PMID- 12815707
TI  - Gene expression profiling of ciliary neurotrophic factor-overexpressing rat
      striatal progenitor cells (ST14A) indicates improved stress response during the
      early stage of differentiation.
AB  - Neuronal progenitor cells delivering neurotrophic factors are a promising
      therapeutic tool for treatment of neurodegenerative diseases. Although several
      promising results have come from studies in different animal models, detailed
      knowledge of the action of neurotrophic factors in the CNS is still lacking. A
      clonally derived, immortalized rat striatal cell line (ST14A) expressing ciliary
      neurotrophic factor (CNTF) offers a stable and controlled background with which
      to analyze CNTF actions on the transcriptional level in CNS progenitor cells. To
      identify early transcriptional changes induced by CNTF expression, we transfected
      the CNTF gene into ST14A cells, which differentiate at the nonpermissive
      temperature of 39 degrees C via suppression of the immortalizing SV40 large T
      antigen. This shows a CNTF-dependent hypoxic/ischemic stress response during the
      earliest stage of differentiation, with expression of specific transcripts and
      evidence of translational repression leading to decreased protein synthesis in
      the transfected cells. This process is mediated by the Ras/MAP kinase pathway and
      is accompanied by impaired proliferation and metabolism as well as signs of
      neuronal differentiation. The stress-like response in the early stage of
      differentiation improves the ability of the transfected cells to respond to and
      cope with a stressful environment in vivo. The present data indicate higher
      viability, longer life, and greater differentiation capacity of CNTF-ST14A cells
      if they are used for transplantation. We conclude that the stress-like response
      during the early stage of differentiation improves the ability of the CNTF-ST14A
      cells to respond and adapt to a stressful environment, which renders them useful
      candidate cells for in vivo trials of treatment for neurodegenerative diseases in
      animal models, e.g., of Huntington's disease.

PMID- 12815708
TI  - Spontaneous central nervous system remyelination is not altered in NFH-lacZ
      transgenic mice after chemical demyelination.
AB  - Harmonious functioning of the nervous system depends on neuron-glia interactions,
      particularly between the axons and their myelinating cells, i.e.,
      oligodendrocytes (OL) in the central nervous system (CNS). In human demyelinating
      diseases such as multiple sclerosis (MS), demyelination may be associated with
      axonal damage, but alterations of the axonal cytoskeleton, which is composed
      mainly of neurofilaments (NF) and microtubules, are largely unknown, as are the
      consequences on remyelination. In a model of demyelination induced by
      lysophosphatidylcholine (LPC), we have shown that demyelination was correlated
      with a decrease in NF immunolabelling, and that these axonal abnormalities were
      reduced by platelet-derived growth factor (PDGF)-enhanced remyelination in adult
      rats. We have analysed the spontaneous remyelination after LPC stereotaxic
      injection in the CNS of transgenic NFH-lacZ mice, which present axonal atrophy
      caused by abnormal distribution of NF, associated with hypermyelination in the
      PNS, and normal myelin thickness in the CNS. Axonal atrophy in the CNS of NFH
      lacZ mice was confirmed, but it was not worsened by demyelination. On the
      contrary, demyelination induced axonal atrophy in wild-type mice, demonstrating
      that NF are essential for axonal calibre determination. Moreover, an efficient
      spontaneous remyelination occurred in NFH-lacZ as well as in wild-type mice,
      indicating that the NF are not necessary for CNS remyelination. These findings
      point out that NF modifications observed in MS may not be responsible for the
      lack of remyelination in this disease.

PMID- 12815709
TI  - Expression of Foxp2, a gene involved in speech and language, in the developing
      and adult striatum.
AB  - Many members of the forkhead/winged helix transcriptional factors are known to be
      regulators of embryogenesis. Mutations of the Fox gene family have been
      implicated in a range of human developmental disorders. Foxp2, a member of the
      Fox gene family, has recently been identified as the first gene that is linked to
      an inherited form of language and speech disorder. To elucidate the anatomical
      basis of language processing in the brain, we have examined the expression
      pattern of Foxp2 gene and its homologous gene, Foxp1, in the rat brain through
      development. Expression of Foxp2 mRNA was detected in the ventral telencephalon
      as early as embryonic day 13. Foxp2 mRNA was expressed primarily in
      differentiated cells of the lateral ganglionic eminence (striatal primordium). Of
      particular interest was that the developmental expression of Foxp2 followed a
      compartmental order in the striatum. Patches containing high levels of Foxp2 were
      aligned with patches enriched in mu-opoid receptor, a marker for striosomal
      cells, in the striatum through postnatal development. Conversely, Foxp2-positive
      patches were devoid of calbindin-D28k, a maker for striatal matrix cells.
      Therefore, Foxp2 was preferentially expressed in striosomal compartment in the
      striatum during development. In the mature striatum, Foxp2 expression was
      maintained in striosomes, although its expression level was reduced. In contrast
      to Foxp2, Foxp1 was expressed in both the striosomal and matrix compartments in
      the striatum through development. The striatum is known to be involved in the
      process of procedural memory, and mutation of Foxp2 results in neurological
      disorders of language and speech. Given the preferential expression of Foxp2 in
      the striosomal compartment, the striatum, particularly the striosomal system, may
      participate in neural information processing for language and speech. Our
      suggestion is consistent with the declarative/procedural model proposed by Ullman
      and colleagues (Ullman et al. [1997] J. Cogn. Neurosci. 9:266-276; Ullman [2001]
      Nat. Rev. Neurosci. 2:717-726), in which the procedural memory-dependent mental
      grammar is rooted in the basal ganglia and the frontal cortex and the declarative
      memory-dependent mental lexicon is rooted in the temporal lobe.

PMID- 12815710
TI  - Cloning and expression of the rat BACE1 promoter.
AB  - The pathogenic processing of the amyloid precursor protein (APP) into beta
      amyloid peptides, which give rise to beta-amyloid plaques in the brains of
      Alzheimer's disease patients, requires the enzymatic activity of the beta-site
      APP-cleaving enzyme 1 (BACE1). We report the cloning and sequence of a 1.5-kb DNA
      fragment upstream of the coding sequence of the rat BACE1 gene and the
      construction of a BACE1 promoter/luciferase reporter construct. The basal
      activity of this promoter construct was highest in neuronal cell lines such as
      BE(2)-C and PC12 and in the pancreatic cell line AR42J, somewhat lower in rat
      primary neurons, and astrocytic and microglial cultures, very low in hepatocytes,
      and almost absent in fibroblasts and in the monocyte-macrophage cell line
      RAW264.7. The first 600 bp of this promoter are highly conserved among rat,
      mouse, and human, suggesting that this region contains regulatory elements that
      modulate BACE1 transcription. Indeed, this fragment contains several putative
      transcription factor binding sites such as MZF1, Sp1, four GATA-1 sites, and one
      YY1 site. Directed mutagenesis of GATA-1 elements led to altered luciferase
      expression, indicating that these sites are involved in the regulation of BACE1
      transcription. Additionally, the analysis of promoter activities of deletion
      mutants suggests the presence of activators of BACE1 transcription between bases 
      514 to -753 and of suppressor elements between bases -754 and -1541. The BACE1
      promoter sequence data and the constructs described here will be useful to
      identify factors that influence the expression of BACE1 in experimental paradigms
      in vitro.

PMID- 12815711
TI  - Fractalkine protein localization and gene expression in mouse brain.
AB  - Few chemokines are expressed constitutively in the brain at detectable levels;
      amongst them is fractalkine. We analyzed the distribution of fractalkine in the
      mouse brain with the aim of giving a neuroanatomical support to the study of its
      physiological function. To this end, we carried out an analysis of fractalkine
      protein localization and gene expression. An anti-fractalkine antibody was
      produced and used to perform an immunohistochemical study. The results indicated
      a high level of fractalkine protein in cortex, hippocampus, basal ganglia, and
      olfactory bulb. In particular, the presence of abundant immunoreactive neurons
      was observed in layers II, III, V, and VI of the cortex. In the hippocampus, the
      CA1 region was the most intensely labeled, but immunoreactive neurons were
      present also in CA2 and CA3, whereas in the basal ganglia, immunoreactive cells
      were observed in the caudate putamen. Other brain structures such as the
      brainstem showed a few scattered immunoreactive cells. The presence of
      fractalkine immunoreactive fibers was revealed only in the olfactory bulb and in
      the anterior olfactory nuclei. Gene expression study results, obtained by both
      semiquantitative PCR and in situ hybridization, matched protein localization with
      the highest levels of fractalkine transcript detected in the hippocampus, cortex,
      and striatum. The present study showed that fractalkine protein and mRNA are
      constitutively expressed at a high level in forebrain structure, but are almost
      absent in the hindbrain. Furthermore, localization at the cellular body level
      would suggest a paracrine or cell-to-cell interaction role for fractalkine more
      than a neurotransmission modulatory function.

PMID- 12815712
TI  - Altered astrocyte calcium homeostasis and proliferation in theTs65Dn mouse, a
      model of Down syndrome.
AB  - Genes from the Down syndrome (DS) critical region of human chromosome 21, which
      contribute to the pathology of DS, are also found on mouse chromosome 16. Several
      animal models of DS with triplication of genes from the DS critical region have
      been generated, including mouse trisomy 16 (Ts16) and a partial trisomic mouse,
      Ts65Dn. Using computer-assisted imaging of fura-2 fluorescence, we found an
      elevation of intracellular cytoplasmic calcium in cortical astrocytes from
      neonatal Ts65Dn mouse brain, similar to that observed previously in embryonic
      Ts16 astrocytes. Furthermore, astrocytes from both Ts65Dn and Ts16 cortex fail to
      respond to the anti-proliferative actions of glutamate. These results suggest
      that defective regulation of cell proliferation and cellular calcium can result
      from triplication of DS critical region genes.

PMID- 12815713
TI  - Early induction of secondary injury factors causing activation of calpain and
      mitochondria-mediated neuronal apoptosis following spinal cord injury in rats.
AB  - To investigate a potential relationship between calpain and mitochondrial damage
      in spinal cord injury (SCI), a 40 gram-centimeter force (g-cm) injury was induced
      in rats by a weight-drop method and allowed to progress for 4 hr. One-centimeter
      segments of spinal cord tissue representing the adjacent rostral, lesion, and
      adjacent caudal areas were then removed for various analyses. Calcium green 2-AM
      staining of the lesion and penumbra sections showed an increase in intracellular
      free calcium (Ca(2+)) levels following injury, compared with corresponding tissue
      sections from sham-operated (control) animals. Western blot analysis showed
      increased calpain expression and activity in the lesion and penumbra segments
      following SCI. Double-immunofluorescent labeling indicated that increased calpain
      expression occurred in neurons in injured segments. Western blot analysis also
      showed an increased Bax:Bcl-2 ratio, indicating the induction of the mitochondria
      mediated cell death pathway in the lesion and penumbra. The morphology of
      mitochondria was altered in lesion and penumbra following SCI: mostly hydropic
      change (swelling) in the lesion, with the penumbra shrunken or normal. At 4 hr
      after induction of injury, a substantial amount of cytochrome c had been released
      into the cytoplasm, suggesting a trigger for apoptosis through caspase 3
      activation. Neuronal death after 4 hr of injury was detected by a combined TUNEL
      and double-immunofluoresence assay in the lesion and penumbra sections of injured
      cord, compared with sham controls. These results suggest that an early induction
      of secondary factors is involved in the pathogenesis of SCI. The increased Ca(2+)
      levels could activate calpain and mediate mitochondrial damage leading to
      neuronal death in lesion and penumbra following injury. Thus, secondary injury
      processes mediating cell death are induced as early as 4 hr after the injury, and
      calpain and caspase inhibitors may provide neuroprotection.

PMID- 12815714
TI  - Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: modulation
      by inhibitors of PI3 kinase and MEK.
AB  - Parkinson's disease is a neurodegenerative disorder associated with the selective
      death of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF)
      can protect dopaminergic neurons in several parkinsonian models. We used the
      dopaminergic cell line MN9D to explore the mechanisms underlying GDNF-mediated
      protection against the neurotoxin 6-hydroxydopamine (6-OHDA). MN9D cell viability
      was decreased 24 hr after a 15-min exposure to 6-OHDA (50-1000 microM) as
      revealed by staining with Hoechst reagent and Trypan blue. The addition of GDNF
      (10 ng/ml) before, during, and after exposure to 6-OHDA significantly increased
      the number of viable cells as assessed by Hoechst staining. In contrast, 6-OHDA
      induced cell membrane damage was unaffected as measured by Trypan blue exclusion.
      The PI3K specific inhibitor LY294002 (10-50 microM) blocked GDNF-mediated
      protection against nuclear condensation, as did the MAPK kinase (MEK) inhibitor
      U0126 (5- 20 microM). These studies suggest that GDNF can protect dopaminergic
      cells against some but not all aspects of 6-OHDA-induced toxicity by acting
      through both PI3K and MAPK signaling pathways.

PMID- 12815715
TI  - Hemin induces an iron-dependent, oxidative injury to human neuron-like cells.
AB  - Hemin is released from hemoglobin after CNS hemorrhage and is present at high
      micromolar concentrations in intracranial hematomas. This highly reactive
      compound is potentially cytotoxic via a variety of oxidative and nonoxidative
      mechanisms. However, despite its clinical relevance, little is known of its
      effect on neuronal cells. In this study, we tested the hypotheses that hemin is
      toxic to human neurons at physiologically relevant concentrations and that its
      toxicity is iron dependent and oxidative. A homogeneous population of neuron-like
      cells was produced by sequential treatment of SH-SY5Y cells with retinoic acid
      and brain-derived neurotrophic factor, using the protocol of Encinas et al. Hemin
      exposure for 24 hr resulted in cell death that progressively increased between 3
      and 30 microM (EC(50) approximately 10 microM); protoporphyrin IX, the iron-free
      congener of hemin, was not toxic. Cell death commenced at 14 hr and was preceded
      by a marked increase in cellular reactive oxygen species (ROS). Most injury and
      ROS production were prevented by concomitant treatment with an equimolar
      concentration of the lipid-soluble iron chelator phenanthroline; the water
      soluble chelator deferoxamine was also effective at concentrations of 0.1 mM or
      higher. Heme oxygenase-2 was constitutively expressed by these cells, and heme
      oxygenase-1 was induced by hemin. Heme oxygenase inhibition attenuated ROS
      generation and reduced injury by about one-third. Cell death was also prevented
      with the sulfhydryl reducing agents glutathione and mercaptoethanol. Nuclear
      morphology in the hours prior to cell lysis revealed a predominantly homogenous
      staining pattern; the percentage of fragmented nuclei was increased only at 4 hr
      and then accounted for only 1.45% +/- 0.25% of cells. The general caspase
      inhibitor zVAD-fmk had no effect on cell viability. These results suggest that
      hemin is toxic to human neuron-like cells at concentrations that are less than 3%
      of those observed in intracranial hematomas. In this model, its toxicity is iron
      dependent, oxidative, and predominantly necrotic.

PMID- 12815716
TI  - Motor cortical control of cardiovascular bulbar neurones projecting to spinal
      autonomic areas.
AB  - There is evidence that the motor cortex is involved in cardiovascular adjustments
      associated with somatic motor activity, as it has functional connections with the
      ventrolateral medulla, a brainstem region critically involved in the control of
      blood pressure and the regulation of plasma catecholamine levels. The
      ventrolateral medulla sends projections to the spinal intermediolateral nucleus,
      where preganglionic neurones controlling heart and blood vessels (T2 segment) and
      adrenal medulla (T8 segment) are found. The aim of the present study was to
      determine whether electrical stimulation of the rat motor cortex induces
      cardiovascular responses and Fos expression in ventrolateral medulla neurones
      projecting to the T2 and T8 segments. After a set of experiments designed to
      record cardiovascular parameters (blood pressure and plasma catecholamine
      levels), injections of retrograde tracer (Fluorogold) were performed in the
      intermediolateral nucleus of two groups of rats, at the T2 or at the T8 segmental
      levels. Five days later, the motor cortex was stimulated in order to induce Fos
      expression in the ventrolateral medulla. Stimulation of the motor cortex induced:
      (1). hypotension and a significant decrease in plasma noradrenaline levels, and
      (2). a significant increase in the number of the double-labelled neurones in the
      rostral ventrolateral medulla projecting to T2. These data demonstrate that
      cardiovascular adjustments, preparatory to, or concomitant with, motor activity
      may be initiated in the motor cortex and transmitted to cardiac and vasomotor
      spinal preganglionic neurones, via the ventrolateral medulla.

PMID- 12815717
TI  - Checkpoint signaling: epigenetic events sound the DNA strand-breaks alarm to the
      ATM protein kinase.
AB  - The ATM protein kinase is centrally involved in the cellular response to ionizing
      radiation (IR) and other DNA double-strand-break-inducing insults. Although it
      has been well established that IR exposure activates the ATM kinase domain, the
      actual mechanism by which ATM responds to damaged DNA has remained enigmatic.
      Now, a landmark paper provides strong evidence that DNA-strand breaks trigger
      widespread activation of ATM through changes in chromatin structure (1). This
      review discusses a checkpoint activation model in which chromatin perturbations
      lead to the conversion of inactive ATM domains to phosphorylated, active ATM
      monomers. The new findings underscore the critical importance of epigenetic
      events in genome function and surveillance in mammalian cells.

PMID- 12815718
TI  - Pathways of intracellular communication: tetrapyrroles and plastid-to-nucleus
      signaling.
AB  - Retrograde plastid-to-nucleus signaling plays a central role in coordinating
      nuclear and plastid gene expression. The gun (genomes uncoupled) mutants of
      Arabidopsis have been used to demonstrate that Mg-protoporphyrin (Mg-Proto) acts
      as a plastid signal to repress the transcription of nuclear photosynthesis genes
      (1). It is unclear how Mg-Proto triggers repression, but several components of
      this pathway have been recently identified. These include the products of GUN4
      and GUN5. GUN5 is the ChlH subunit of Mg-chelatase, which produces Mg-Proto, and
      GUN4 is a regulator of ChlH activity (2). GUN4 might also play a role in
      photoprotection and in the trafficking of Mg-Proto.

PMID- 12815719
TI  - The evolution of floral homeotic gene function.
AB  - Plant MADS-box genes encode transcriptional regulators that are critical for a
      number of developmental processes. In the angiosperms (the flowering plants),
      these include the specification of floral organ identities, flowering time and
      fruit development. It appears that the MADS box gene family has undergone
      considerable gene duplication and sequence divergence within the angiosperms.
      Here I discuss the possibility that these events have allowed the recruitment of
      these genes to new developmental pathways in particular angiosperm lineages.
      Recent analyses of sequence changes, expression patterns and, in a few cases,
      gene function are beginning to provide tantalizing evidence for deciphering when
      and how such genetic diversification has led to particular morphological
      innovations. In the future, comparative studies of large numbers of species will
      be required to assess the extent of such variation as well as to fully understand
      the mechanisms by which evolution of these developmental regulators has played a
      role in shaping new morphologies.

PMID- 12815720
TI  - Epigenomic replication: linking epigenetics to DNA replication.
AB  - The information contained within the linear sequence of bases (the genome) must
      be faithfully replicated in each cell cycle, with a balance of constancy and
      variation taking place over the course of evolution. Recently, it has become
      clear that additional information important for genetic regulation is contained
      within the chromatin proteins associated with DNA (the epigenome). Epigenetic
      information also must be faithfully duplicated in each cell cycle, with a balance
      of constancy and variation taking place during the course of development to
      achieve differentiation while maintaining identity within cell lineages. Both the
      genome and the epigenome are synthesized at the replication fork, so the events
      occurring during S-phase provide a critical window of opportunity for eliciting
      change or maintaining existing genetic states. Cells discriminate between
      different states of chromatin through the activities of proteins that selectively
      modify the structure of chromatin. Several recent studies report the localization
      of certain chromatin modifying proteins to replication forks at specific times
      during S-phase. Since transcriptionally active and inactive chromosome domains
      generally replicate at different times during S-phase, this spatiotemporal
      regulation of chromatin assembly proteins may be an integral part of epigenetic
      inheritance.

PMID- 12815721
TI  - Influenza type A in humans, mammals and birds: determinants of virus virulence,
      host-range and interspecies transmission.
AB  - The virulence of a virus is determined by its ability to adversely affect the
      host cell, host organism or population of host organisms. Influenza A viruses
      have been responsible for four pandemics of severe human respiratory disease this
      century. Avian species harbour a large reservoir of influenza virus strains,
      which can contribute genes to potential new pandemic human strains. The
      fundamental importance of understanding the role of each of these genes in
      determining virulence in birds and humans was dramatically emphasised by the
      recent direct transmission of avian influenza A viruses to humans, causing fatal
      infection but not community spread. An understanding of the factors involved in
      transmission between avian and mammalian species should assist in the development
      of better surveillance strategies for early recognition of influenza A virus
      strains having human pandemic potential, and possibly in the design of anti-viral
      strategies.

PMID- 12815722
TI  - The story of cell fusion: big lessons from little worms.
AB  - The ability of two or more cells to unite to form a new syncytial cell has been
      utilized in metazoans throughout evolution to form many complex organs, such as
      muscles, bones and placentae. This requires migration, recognition and adhesion
      between cells together with fusion of their plasma membranes and rearrangement of
      their cytoplasmic contents. Until recently, understanding of the mechanisms of
      cell fusion was restricted to fusion between enveloped viruses and their target
      cells. The identification of new factors that take part in developmental cell
      fusion in C. elegans opens the way to understanding how cells fuse and what the
      functions of this process are. In this review, we describe current knowledge on
      the mechanisms and putative roles of developmental cell fusion in C. elegans and
      how cell fusion is regulated, together with other intercellular processes to
      promote organogenesis.

PMID- 12815723
TI  - Reconstructing eukaryotic NAD metabolism.
AB  - In addition to its well-known role as a coenzyme in oxidation-reduction
      reactions, the distinct role of NAD as a precursor for molecules involved in cell
      regulation has been clearly established. The involvement of NAD in these
      regulatory processes is based on its ability to function as a donor of ADP
      ribose; NAD synthesis is therefore required to avoid depletion of the
      intracellular pool. The rising interest in the biosynthetic routes leading to NAD
      formation and the highly conserved nature of the enzymes involved prompted us to
      reconstruct the NAD biosynthetic routes operating in distinct eukaryotic
      organisms. The evidence obtained from biochemical and computational analysis
      provides a good example of how complex metabolic pathways may evolve. In
      particular, it is proposed that the development of several NAD biosynthetic
      routes during evolution has led to partial functional redundancy, allowing a
      given pathway to freely acquire novel functions unrelated to NAD biosynthesis.

PMID- 12815724
TI  - The pleiotropic functions of the Y-box-binding protein, YB-1.
AB  - The Y-box-binding protein (YB-1) represents the most evolutionary conserved
      nucleic-acid-binding protein currently known. YB-1 is a member of the cold-shock
      domain (CSD) protein superfamily. It performs a wide variety of cellular
      functions, including transcriptional regulation, translational regulation, DNA
      repair, drug resistance and stress responses to extracellular signals. As a
      result, YB-1 expression is closely associated with cell proliferation. In this
      review, we will begin by briefly describing the characteristics of YB-1 and will
      then summarize the pleiotropic functions brought about via DNA-RNA transaction
      and protein-protein interactions. In addition, we will discuss the diverse range
      of potential physiological and pathological functions of YB-1.

PMID- 12815725
TI  - Genes, neurons and codes: remarks on biological communication.
AB  - I examine critically the application of information-theoretic ideas to biological
      communication during embryonic development and in the functioning central nervous
      system (CNS). I show that intercellular communication relies mostly on simple
      signals whose role is to effect a selection among predetermined cellular states.
      Hence, a crucial role is played by cellular memory, which stabilizes such states.
      Memory in cells is partly located in the nuclear DNA; no less important however
      is (phenotypic) memory lying in the cell's organelles and compartments. Because
      of combinatorial effects in gene expression patterns, cell memory is an
      enormously powerful mechanism, which also underlies plasticity, and thus
      constitutes the factor unifying genetic determination, plasticity and learning.
      Communication in the CNS is analyzed in some detail: here, cellular memory is
      embodied in anatomy (i.e., cell shape) and neurochemistry. These are the major,
      relatively "static" factors affecting the routing of neural impulses in the adult
      CNS. In addition, however, faster channeling is also required: action potentials
      must be directed to their targets along a few of exponentially many paths, and
      this dynamic routing is crucial for proper operation. I suggest that collective
      oscillatory modes may play a role in solving this addressing problem, in the same
      way that the clock signal gates the operation of man-made computers.

PMID- 12815726
TI  - The role of class I HLH genes in neural development--have they been overlooked?
AB  - Helix-loop-helix (HLH) genes encode for transcription factors affecting a whole
      variety of developmental programs, including neurogenesis. At least seven
      functional classes (denoted I to VII) of HLH genes exist, (1) with subclass
      members exhibiting homo- and heterodimerisation for proper DNA binding and
      transcriptional regulation of downstream target genes. In the developing nervous
      system, members of class II, V and VI have been most extensively studied
      concerning their roles in neural programming. In contrast, the function of class
      I proteins (such as E12 and E47) is poorly defined and the orthodox view
      relegates them to general dimerisation duties that are necessary for the activity
      of the other classes. However, closer scrutiny of the spatiotemporal expression
      patterns of class I factors, combined with recent biochemical evidence, would
      suggest that class I proteins possess specific functions during early neural
      differentiation. This essay supports this possibility, in addition to putting
      forward the hypothesis that, outside their general dimerisation activity, class I
      genes have independent roles in regulating neurogenesis.

PMID- 12815727
TI  - What's your position? the Xenopus cement gland as a paradigm of regional
      specification.
AB  - The correct positioning of organs during embryonic development requires multiple
      cues. The Xenopus cement gland is a mucus-secreting epithelium that is a simple
      model for organogenesis, allowing detailed analysis of this complex process. The
      cement gland forms at a conserved anterior position, where embryonic ectoderm and
      endoderm touch. In all deuterostomes, this region will form the stomodeum
      (primitive mouth) and, in some aquatic larva, will also form a cement gland. In
      recent years, a model has been put forward suggesting that an intermediate level
      of BMP signaling in the ectoderm leads to cement gland formation. We propose an
      alternative model whereby, during gastrulation, the cement gland (CG) is
      positioned by the overlap of three domains, corresponding to anterodorsal
      identity (AD), ventrolateral identity (VL), and ectodermal outer layer identity
      (EO), defining the equation (AD + VL + EO = CG). Anterodorsal identity requires a
      contribution by the transcription factor Otx2 while ventrolateral identity
      requires the BMP4 signaling pathway. These postional cues are integrated to
      activate cement gland differentiation. This integration appears to require
      intermediate steps, including expression of pitx genes, and members of the
      ATF/CREB and Ets transcription factor families.

PMID- 12815728
TI  - Interview with J. T. Bonner.

PMID- 12815729
TI  - A link between cholesterol, synapse plasticity, degeneration and neurological
      disorders: reinvention or integration?

PMID- 12815731
TI  - DNA stability and schizophrenia in twins.
AB  - The goal of these experiments was to understand DNA changes relevant to
      schizophrenia. This work compared DNA of monozygotic (MZ) twins surrounding
      (CAG)(n) repeating sequences, and characterized the relationship between fragile
      sites and schizophrenia. Twelve twin-pairs, previously classified as MZ and 18
      unrelated sib-pairs, from seven families were studied. Eight twin-pairs were
      affected by schizophrenia, four concordantly and four discordantly. DNA
      comparisons were made using profiles of electrophoretic size fractionations of
      PCR amplified (CAG)(n) containing genomic fragments. These profiles were
      generated by a new method, developed by us, called targeted genomic differential
      display (TGDD). Surprisingly, the number of peak profile differences in MZ twin
      pairs discordant for schizophrenia was greater than the concordantly ill twins
      and the well twins and, in some cases, overlapped the range of sib-pairs. These
      results might mean that some twins were not MZ but it was not possible to
      definitively test these samples for zygosity. Alternatively, the results might be
      explained as an increased mutation rate (or genomic instability) around (CAG)(n)
      sites in individuals afflicted with schizophrenia. Also, we uncovered an
      association of schizophrenia (i.e., a linkage of chromosomal abnormalities and
      gene localizations) with fragile sites spread throughout the genome (chi(2), P =
      0.001). Furthermore, it appears that an increasing number of genes linked to
      schizophrenia are associated with (CAG)(n) sequences. Fragile sites and (CAG)(n)
      repeat sequences are known to be unstable. We speculate the association of
      genomic instability with schizophrenia accounts for seemingly disparate
      biological and environmental factors that influence disease occurrence.

PMID- 12815732
TI  - Family-based association study of markers on chromosome 22 in schizophrenia using
      African-American, European-American, and Chinese families.
AB  - Several studies suggest that loci at chromosome 22q11.2-q13 might be linked to
      susceptibility to schizophrenia. Here we performed family-based association
      studies on chromosome 22q using 12 DNA microsatellite markers in African
      American, European-American, and Chinese pedigrees. The marker D22S683 showed
      significant linkage and association with schizophrenia in not only the European
      American sample but also in a combined sample (European-American and Chinese
      samples). Notably, D22S683 is located nearby and between D22S278 and D22S283,
      which have shown linkage and association to schizophrenia in prior reports.
      However, we found no significant association for the African-American sample. In
      conclusion, our data provide further support for the idea that the region around
      D22S683 contains a susceptibility gene for schizophrenia.

PMID- 12815734
TI  - Initial genome-wide scan for linkage with schizophrenia in the Japanese
      Schizophrenia Sib-Pair Linkage Group (JSSLG) families.
AB  - To determine if there are common genes that contribute to the susceptibility for
      schizophrenia, first-stage genome-wide scan was carried out by genotyping 417
      short-tandem repeat (STR) markers in 338 individuals from 130 families with 148
      affected sib-pairs identified at 16 sites nationwide in Japan. Data was from the
      Japanese Schizophrenia Sib-pair Linkage Group (JSSLG), which is a multi-site
      collaborative study group established to create a national resource for genetic
      studies of schizophrenia in Japan. All subjects were Japanese, and the probands
      and their siblings had schizophrenia. Multipoint non-parametric linkage analysis
      and exclusion mapping were performed with GENEHUNTER software. Simulation studies
      suggested that in the absence of linkage we could expect one multipoint maximum
      LOD score (MLS) of 1.9 per genome scan. An MLS of 3.7 would be expected only once
      in every 20 genome scans and thus corresponds to a genome-wide significance of
      0.05. No loci in the initial screen fulfilled the criteria for significant or
      suggestive evidence for linkage. Ten chromosomes (1, 2, 3, 4, 5, 8, 9, 14, 17,
      and 20) had at least one region with a nominal P value < 0.05. Susceptibility
      genes with lambdas of 3 and 2 were excluded from 98 and 70% of the genome,
      respectively. Our results suggest that common genes that contribute significantly
      to susceptibility for schizophrenia are unlikely to exist in the Japanese
      population.

PMID- 12815733
TI  - Mutation screening of the Homer gene family and association analysis in
      schizophrenia.
AB  - Homer proteins are a group of proteins that regulate group 1 metabotropic
      glutamate receptor function. As altered glutamate function has been implicated in
      many neuro psychiatric disorders, particularly schizophrenia, we have screened
      all three known Homer genes for sequence variation for use under the candidate
      gene association paradigm. We found seven SNPs, including three in exons. Of
      these, none was non-synonymous. Allele frequencies of all the detected SNPs were
      estimated in DNA pools of 368 schizophrenics and 368 controls. Only one (Homer 1
      IVS4 + 18A > G) was associated with schizophrenia in this sample, a finding
      confirmed by individual genotyping (P = 0.01). However, in our extended sample of
      680 cases and 671 controls, the evidence for association diminished (P = 0.05).
      Our results suggest it is unlikely that sequence variants in the Homer genes
      contribute to the aetiology of schizophrenia, but the variants we identified are
      plausible candidates for other neuropsychiatric phenotypes.

PMID- 12815735
TI  - Aggressive behavior in schizophrenia is associated with the low enzyme activity
      COMT polymorphism: a replication study.
AB  - We have previously reported that increased aggressive behavior in schizophrenic
      patients may be associated with a polymorphism at codon 158 of the catechol O
      methyltransferase (COMT) gene that encodes a low enzyme activity variant. The
      finding has been replicated by one group, but not others. The discordant findings
      could be due to statistical errors or methodological issues in the assessment of
      aggressive/violent behavior. Consequently, additional studies are needed.
      Patients with schizophrenia (SZ) were assessed for violent behavior using the
      Lifetime History of Aggression (LHA) scale, an 11-item questionnaire that
      includes Aggression, Self-Directed Aggression, and Consequences/Antisocial
      Behavior subscales. DNA was genotyped for the COMT 158 polymorphism, as well as a
      functional polymorphism in the monoamine oxidase A (MAOA) gene promoter. Similar
      to our previously reported findings, a statistically significant association was
      found between aggressive behavior in SZ and the COMT 158 polymorphism; mean LHA
      scores were higher in subjects homozygous for 158Met, the low enzyme activity
      COMT variant (F(2,105) = 5.616, P = 0.005). Analysis of the major LHA subscales
      revealed that the association with 158Met was due to high scores on the
      Aggression, and Self-Directed Aggression subscales, but not the
      Consequences/Antisocial Behavior subscale. No significant association was
      detected for the MAOA gene alone. Our findings provide further support that COMT
      is a modifying gene that plays a role in determining interindividual variability
      in the proclivity for outward and self-directed aggressive behavior found in some
      schizophrenic patients.

PMID- 12815736
TI  - Relationship between catechol-O-methyltransferase polymorphism and treatment
      resistant schizophrenia.
AB  - Catechol-O-methyltransferase (COMT) plays a crucial role in the regulation of
      central dopaminergic systems. We examined the allelic association of a functional
      polymorphism of the COMT gene with the clinical manifestations and the response
      to antipsychotics of 100 schizophrenic patients and 201 healthy controls from the
      general Japanese population. No statistically significant difference was observed
      in the allele and genotype frequencies between the schizophrenic patients and the
      healthy controls. The daily neuroleptic dosage that patients received during
      their maintenance therapy was significantly higher in patients with the L/L
      genotype than in the other patients (P < 0.05). The present results suggest that
      the presence of the COMT genotype does not help in evaluating the susceptibility
      to the development of schizophrenia, but that it may help in the estimation of
      treatment-resistant features of schizophrenia.

PMID- 12815737
TI  - No evidence of molecular heterosis at the dopamine D2 receptor gene locus for
      smoking in schizophrenia.

PMID- 12815738
TI  - Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia.
AB  - People with deletion of the chromosome 22q11 region associated with velo cardio
      facial syndrome (VCFS) have a remarkably high risk of developing schizophrenia.
      Recently, the gene proline dehydrogenase (PRODH) which maps to 22q11 and is also
      an excellent functional candidate gene for psychosis, has been reported to show
      genetic association with schizophrenia. We have screened all the exons and
      adjacent intronic sequences of PRODH for the presence of sequence variation in 14
      DSM IV schizophrenic subjects. Similarly, we also screened all putative exons of
      a sequence that is similar to proline dehydrogenase (PsPRODH) and which also maps
      within the deleted region. A total of nine single nucleotide polymorphisms (SNPs)
      were identified in PRODH, eight of which were exonic, while in PsPRODH, five SNPs
      were identified, one of which was in a putative exon. All samples were tested for
      association in a pooled sample of 368 DSM IV diagnosed schizophrenic subjects and
      368 matched controls. None of the variants identified in PRODH gave even modest
      evidence for allelic association (P < 0.1). In PsPRODH, two variants (-3864G > A
      and 226G > A) gave P values < 0.1. These were individually genotyped in the same
      subjects that had been used to construct the pools. Although a trend for
      association was confirmed, neither showed evidence for association at the P </=
      0.05 level. These results do not suggest that PRODH or PsPRODH contribute to the
      aetiology of schizophrenia, and that the putative schizophrenia susceptibility
      gene in 22q11 remains unknown.

PMID- 12815739
TI  - Association between Val108/158 Met polymorphism of the COMT gene and
      schizophrenia.
AB  - Schizophrenia is a complex disorder with a multifactorial polygenic inheritance
      with several genes conferring susceptibility at many genetic locations, each with
      a small effect. An attractive candidate gene for schizophrenia is the catechol-O
      methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal
      cortical function. A missense G to A mutation in this gene that results in a
      substitution of Methionine (Met) for Valine (Val) at codon 108/158 (Val(108/158)
      Met) has recently been identified in association to schizophrenia. We compared
      allele frequencies of the variant Val allele between 96 schizophrenia cases and
      80 normal controls. We selected controls from a similar pool to cases in
      ethnicity and gender. The frequency of the Val allele was significantly higher in
      schizophrenia cases compared to controls (0.620 vs. 0.506; P = 0.043).
      Calculation of the population attributable risk suggests that the Val allele
      accounts for as much as 23% of schizophrenia in this population (range: 3-38%).
      These results provide support for a role of this variant in the
      etiopathophysiology of schizophrenia.

PMID- 12815740
TI  - NURR1 promoter polymorphisms: Parkinson's disease, schizophrenia, and personality
      traits.
AB  - We have previously identified mutations in exon three in NURR1 (NR4A2) in two
      patients with schizophrenia (SZ) and one patient with bipolar disease with
      psychotic symptoms. In the present study we analyzed the promoter region of NURR1
      and identified five polymorphic sites: three were found to be in strong linkage
      disequilibrium with a previously identified polymorphic site in the sixth intron.
      One polymorphism of this haplotype and the two other independent polymorphisms
      were investigated for their possible association with SZ and Parkinson's disease
      (PD) by comparing their frequencies in a Swedish material consisting of 134
      subjects with SZ and 207 matched controls and 108 subjects with PD and 125
      matched controls. Exon 1 was also investigated in our Parkinson and control
      material but no variances were found. The distributions of the two most
      informative polymorphisms in the promoter were investigated in an American
      material as well consisting of 141 subjects with SZ and 139 matched controls.
      Furthermore, the identified markers were screened for association with putative
      endophenotypes of SZ in the Swedish material. The distribution of sequence
      variants among the Swedish controls matched for SZ was investigated with regard
      to personality. No significant genotype or allelic association of the three
      sequence variants with SZ or PD was found. Several comparisons regarding
      endophenotypes or personality indicated association at the 5% confidence level,
      although correction for multiple testing rendered none of these findings
      significant. We conclude that the identified polymorphic sites in the human NURR1
      are unlikely to be involved in conferring susceptibility for SZ or PD in our
      patient material.

PMID- 12815741
TI  - Monoamine oxidase B polymorphism, cigarette smoking and risk of Parkinson's
      disease: a study in an Asian population.
AB  - Cigarette smoking is associated with reduced monoamine oxidase B (MAO B)
      activity. Polymorphisms of the MAO B gene may modify the relationship between
      smoking and Parkinson's Disease (PD). We examined the association of MAO B intron
      13 G/A polymorphism and risk of PD, and the modulation of the polymorphism on
      smoking and PD in an Asian study population in Singapore. Two hundred and thirty
      PD patients (mean age 66.0 +/- 9.4 years, 63% men) and 241 age, gender, and race
      matched controls (mean age 64 +/- 9.2 years, 58.9% males) were studied. The
      frequency of G and A alleles in PD and controls was; 66/315 (21.0%) vs. 73/340
      (21.5%) and 249/315 (79.0%) vs. 267/340 (78.5%). For women, the genotype
      frequency in PD and controls was; GG: 7/85 (8.2%) vs. 8/99 (8.1%); GA: 25/85
      (29.4%) vs. 27/99 (27.3%); AA: 53/85 (62.4%) vs. 64/99 (64.6%). For men, allele
      frequency in PD and controls was; A: 118/145 (81.4%) vs. 112/142 (78.9%) and G:
      27/145 (18.6%) vs. 30/142 (21.1%). The allele and genotype frequencies were not
      significantly different between young and late onset PD. The frequency of "ever"
      smokers in PD and controls was 31/230 (13.5%) vs. 52/241 (21.6%), P = 0.02. A
      stepwise logistic regression analysis did not reveal any interaction of smoking
      and the G allele and risk of PD. The MAO B G/A genotype frequency in our Asian
      population was quite different from Caucasians suggesting that ethnicity specific
      effects need to be considered in evaluating gene-environmental interaction.

PMID- 12815742
TI  - Genome wide scan using homozygosity mapping and linkage analyses of a single
      pedigree with affective disorder suggests oligogenic inheritance.
AB  - The present study reports results from a genome scan on a family with bipolar
      affective disorder in which the parents are first cousins and four of the
      offsprings and one grandchild have affective disorder. The study searched for
      risk loci for affective disorder by searching for homozygous segments or more
      complex inherited loci using parametric and non-parametric multipoint linkage
      analysis. In addition dominant, multipoint, affecteds-only linkage analyses were
      performed as a supplement to previous analyses. On chromosomes 2q31.3, 10, 12q24,
      and 21q22.3 evidence for a risk locus was obtained by parametric and/or non
      parametric linkage analyses and by haplotype sharing. As other studies have found
      significant or suggestive linkage to bipolar disorder in these chromosome regions
      this suggests that an oligogenic mode of inheritance is possible in this family
      involving at least some of the loci. Finally, the work discusses whether
      homozygosity mapping using parametric and non-parametric linkage analyses may be
      of value for complex diseases including rare subphenotypes of such disorders.

PMID- 12815743
TI  - Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar
      disorder.
AB  - Linkage of bipolar disorder with 18p11 has been replicated by several
      investigators. A nuclear-encoded mitochondrial complex I subunit gene, NDUFV2, is
      one of the candidate genes in this locus, since the possible pathophysiological
      significance of mitochondrial dysfunction in bipolar disorder has been suggested.
      The objective of our study was to clarify the association between the NDUFV2 gene
      and bipolar disorder. We performed the real-time quantitative reverse
      transcription polymerase chain reaction (RT-PCR) for NDUFV2 mRNA expression in
      lymphoblastoid cell lines derived from patients with bipolar disorder and healthy
      controls. We also screened novel polymorphisms using denaturing high performance
      liquid chromatography (D-HPLC) and PCR-direct sequencing method. Detected five
      single nucleotide polymorphisms (SNPs) were genotyped. A decrease of the
      expression level of NDUFV2 gene was found in patients with bipolar I disorder
      compared with controls (P = 0.006). We also found that the haplotype frequencies
      of the four polymorphisms in the upstream region of NDUFV2 were significantly
      different between bipolar disorders and controls (P = 0.0001). Our findings
      suggest that polymorphisms of the NDUFV2 gene may be one of the genetic risk
      factors for bipolar disorder.

PMID- 12815744
TI  - Association between depressed mood in the elderly and a 5-HTR2A gene variant.
AB  - The aim of this study was to investigate any possible association between
      depressed mood in the elderly and two candidate SNPs in the serotonin system: one
      in the 5-HTR2A gene promotor (-1438 G/A) and one in the 5-HT transporter gene (
      925 C/A). DNA from a population-based Swedish twin sample (N = 1,592; mean age =
      73) was genotyped using Pryosequencing trade mark. An association was found
      between the 5-HTR2A gene promotor polymorphism and depressed mood (OR: 1.5, CI:
      1.1-2.1) for the A/A genotype in the total sample. When the sample was analyzed
      by gender, a significant association (OR: 2.4, CI: 1.4-4.4) was found for males
      and the A/A genotype, but not for females. The 5-HT transporter gene was not
      associated with depressed mood in this elderly population. These results suggest
      that there might be different genetic mechanisms for males and females
      contributing to the development of depressed mood in the elderly.

PMID- 12815745
TI  - Beta-1-adrenergic receptor gene in major depression: influence on antidepressant
      treatment response.
AB  - Noradrenergic dysfunction has been implicated in the development of affective
      disorders. beta-adrenergic receptors (betaARs) mediate the response to
      norephinephrine, are coupled to the cAMP signaling cascade, supposed to be
      altered in their density and/or sensitivity in depression, and down regulated in
      several brain regions after long term treatment with different but not all
      antidepressants. A recently identified functional polymorphism in the beta(1)
      adrenergic receptor (G1165C) leading to the amino acid variation Gly389Arg was
      associated with an enhanced coupling to the stimulatory G(s)-protein and
      increased adenylyl cyclase activation, disturbances which are often observed in
      affective disorders. Therefore, we investigated whether this beta(1)AR
      polymorphism is associated with major depression or with the response to
      antidepressant treatment in a sample of 259 patients compared to 206 healthy
      controls. Although we could not detect an association between the beta(1)AR
      polymorphism and major depression we found a tendency for a relation between CC
      homozygosity and a better and even faster response to antidepressant treatment in
      those patients, which were treated with antidepressants affecting directly or
      indirectly the beta(1)AR system (tricyclic antidepressants, noradrenergic and
      serotonergic specific agents, selective noradrenaline reuptake inhibitors)
      determined by the HAMD and CGI score (P = 0.05). However, after correction for
      multiple testing (Bonferroni) these results did not remain significant.
      Nevertheless, these findings suggest that the presence of the C allele might be
      an indicator for antidepressant treatment response.

PMID- 12815746
TI  - Association analysis of MAOA and COMT with neuroticism assessed by peers.
AB  - There are several reported associations between depressive disorders, panic
      disorder, and obsessive-compulsive disorder (OCD) and a variety of polymorphisms
      in the monoamine oxidase A (MAOA) gene. Associations have also been reported
      between the catechol-O-methyltransferase (COMT) gene and both OCD and bipolar
      depression. However, the role of these markers has not been explored for the
      personality trait of neuroticism (N), a normally distributed quantitative trait,
      which is highly genetically correlated with anxiety and depression and may be a
      vulnerability to either type of disorder. We explored the possible role of MAOA,
      COMT, and their interaction on N using a selected extremes design. From a sample
      of 2,085 individuals, each assessed for N by two independent peers rather than
      using self-report questionnaires, we selected 57 individuals from the top 10% of
      scores, and 62 individuals from the bottom 10%. Using selected extreme low
      subjects as the controls, rather than an unselected control group gives roughly
      twice the power of a standard case-control design. We typed a functional variable
      number tandem repeat (VNTR) in the MAOA gene promoter, and a functional
      polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA
      VNTR were identified on the basis of their size, and their structure examined by
      sequencing analysis. We found weak evidence for association with COMT genotype,
      when the females and males were considered separately, and for MAOA genotype in
      males only. There was no significant interaction between COMT and MAOA.

PMID- 12815747
TI  - Haplotypes at the OPRM1 locus are associated with susceptibility to substance
      dependence in European-Americans.
AB  - Our objective was to investigate the relationship between the gene encoding the
      mu-opioid receptor (OPRM1) and susceptibility to substance dependence in European
      American (EA) and African-American (AA) subjects. Eight single nucleotide
      polymorphisms (SNPs) at the OPRM1 locus, i.e., -2044C/A, -1793T/A, -1699insT, 
      1469T/C, -1320A/G, -111C/T, +17C/T (Ala6Val), and +118A/G (Asn40Asp) were
      genotyped in 676 subjects: 318 EA subjects and 124 AA subjects with substance
      dependence, and 179 EA normal controls, and 55 AA normal controls. Affection
      status was defined by each unique combination of alcohol, cocaine, and opioid
      dependence and analysis of association examined in relation to the possible
      combinations. We used a newly implemented permutation method to evaluate
      statistical significance. In EAs, a significant difference in haplotype frequency
      distributions was found between controls and "alcohol + opioid" dependent
      patients (P = 0.0036). This finding is also supported by logistic regression
      analysis and a simulation method. The frequencies of allele -2044A and haplotypes
      including -2044A are higher in these patients than in controls. In AAs, no
      allele, haplotype, or genotype frequencies were significantly different between
      cases and controls. There were highly significant differences in the allele,
      haplotype, and genotype frequencies between EA and AA controls. Four of the
      variants [-1793T/A, -1699insT, -1320A/G, and -111C/T] are in virtually complete
      linkage disequilibrium (LD) to compose a sequence pattern, which does not
      associate with any of the seven categories of substance dependence. In EAs,
      allele -2044A and haplotypes that include -2044A are the susceptibility allele
      and haplotypes for substance dependence. These findings suggest that OPRM1 may
      play a role in the pathophysiology of substance dependence and this role is
      population- and diagnosis-specific.

PMID- 12815748
TI  - Etiology of the comorbidity between RD and ADHD: exploration of the non-random
      mating hypothesis.
AB  - The present research sought to test the validity of the non-random mating
      hypothesis in a community sample in order to determine whether it contributes
      significantly to the comorbidity between attention-deficit/hyperactivity disorder
      (ADHD) and reading disability (RD) and to test whether the two disorders
      segregate independently. Data were gathered from 394 twin participants of the
      Colorado Learning Disabilities Research Center (CLDRC) and their biological
      parents. Parents were asked to complete retrospective questionnaires regarding
      their own ADHD and RD symptomatology as children, as well as rate their children
      on DSM-IV ADHD symptomatology before age 12. Twin RD was assessed by a composite
      score consisting of several reading measures. Chi-square and correlational
      analyses assessed the presence of non-random mating, as well as whether the two
      disorders were transmitted independently. Non-random mating between those with
      ADHD and those with RD did not significantly contribute to the comorbidity of the
      two disorders. Furthermore, there was some evidence that these two disorders did
      not segregate independently in this sample. These results are consistent with
      recent evidence that ADHD and RD are often comorbid because of significant
      genetic overlap. There was little evidence to support that non-random mating also
      contributes to this comorbidity in the present sample.

PMID- 12815749
TI  - Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention
      deficit/hyperactivity disorder?
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex childhood-onset
      psychiatric disorder characterized by marked symptoms of inattention,
      hyperactivity, and impulsivity. The role of genetic factors in its etiology is
      strongly supported by family, adoption, and twin studies. Although most of the
      molecular studies have investigated the dopamine D4 receptor gene (DRD4) and the
      dopamine transporter gene (DAT1) genes in its etiology, pharmacological and brain
      imaging evidences seem to indicate that genes of the adrenergic system could also
      be attractive for association studies. We investigated a sample of 96 Brazilian
      ADHD children and adolescents and their parents for the ADRA2A MspI polymorphism.
      Although no association with either MspI allele was observed through the
      haplotype relative risk (HRR) analysis, effects of the ADRA2A gene on inattention
      and combined (inattention + hyperactivity/impulsivity) symptom scores were
      detected (U = 222.5, z = 2.19, P = 0.03; and U = 208.5, z = 2.32, P = 0.02,
      respectively). Our results suggest that the ADRA2A gene might have a small effect
      on ADHD susceptibility or that this gene might modulate the severity of the
      disorder. They are also consistent with the noradrenergic theories of ADHD,
      suggesting a role for the alpha2A adrenergic receptors in the disorder.

PMID- 12815750
TI  - Apolipoprotein E Pittsburgh variant is not associated with the risk of late-onset
      Alzheimer's disease in a Spanish population.
AB  - The objective of this study was to assess whether the APOE(Pittsburgh) variant
      (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid
      (Spain). APOE*4P variant is caused by an exonic mutation which results in the
      substitution of proline-28 for leucine-28, only present in APOE*4 alleles. A
      study in a US population associated this APOE variant with an increased risk for
      AD, about five times higher than the risk attributed to APOE*4 carriers overall.
      One hundred and seventeen cases of late-onset AD and 121 matched control subjects
      from Madrid (Spain) were included. We studied the APOE polymorphism and the
      APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels
      using standard protocols. As expected, APOE*4 was significantly overrepresented
      in AD cases. The APOE*4P mutation was observed in heterozygous state in four
      subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher
      risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02-1.12)
      or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02-1.24). There were no
      differences in plasma lipids levels among genotype groups. The mutation frequency
      in controls was higher in our sample than in the US one (1.65 and 0.18%,
      respectively; Fisher test P = 0.049). Our results suggest that this variant is
      not so uncommon in our population and is not directly related to AD, contrary to
      what has been proposed for other populations.

PMID- 12815751
TI  - Parvocellular subparafascicular thalamic nucleus in the rat: anatomical and
      functional compartmentalization.
AB  - The parvocellular subparafascicular thalamic nucleus (SPFp) is located in the
      posterior thalamus, consists of horizontally oriented cells, and extends from
      rostromedial to caudolateral, fusing with the posterior intralaminar nucleus and
      the peripeduncular nucleus. The present study demonstrates a chemoarchitechtonic
      and functional parcellation of the rat SPFp. Analysis of the distributions of the
      neuropeptides galanin, calcitonin gene related peptide (CGRP), substance P, and
      calbindin revealed the existence of a medial and lateral subdivision within SPFp,
      and a possible intermediate subdivision. The medial subdivision contains a dense
      population of galanin-immunoreactive fibers, originating from galanin neurons in
      the lumbosacral spinal cord. In contrast, the lateral subdivision contains CGRP
      positive fibers and neurons. The presence of substance P and calbindin
      immunoreactivity throughout the entire nucleus suggests that these are separate
      subdivisions of SPFp, rather than different subnuclei. The present study also
      investigated the functional association of the separate subdivisions of SPFp for
      male and female rat sexual behavior. In the medial subdivision, Fos-positive
      neurons were activated in males by display of ejaculation and in females by
      vaginocervical stimulation. Thus, Fos induction in medial SPFp appears to reflect
      processing of inputs related to those events. In contrast, sexual behavior did
      not induce Fos in the lateral SPFp. Taken together, the present results indicate
      the existence of separate subdivisions in SPFp that are involved in different
      behavioral functions. The medial SPFp may process inputs important for sexual
      behavior, whereas the lateral SPFp may be involved in convergence of auditory and
      nociceptive inputs important for conditioned fear responses.

PMID- 12815752
TI  - Afferent connections of the parvocellular subparafascicular thalamic nucleus in
      the rat: evidence for functional subdivisions.
AB  - The parvocellular subparafascicular nucleus of the thalamus (SPFp) consists of
      separate subdivisions, i.e., a medial portion containing galanin-immunoreactive (
      IR) axons and a lateral portion containing calcitonin gene related peptide (CGRP)
      IR neurons and fibers. These subdivisions appear to have distinct functional
      roles. In particular, ejaculation-induced Fos expression is expressed in the
      medial SPFp. Hence, it was hypothesized that medial SPFp is involved in relay of
      copulation-related information. In contrast, lateral SPFp is involved in the
      processing of auditory and visual signals involved in fear-conditioned responses.
      Here we tested the hypothesis that medial and lateral subdivisions of SPFp
      receive different sets of afferents and that these differences contribute to the
      separate functional roles of the two subdivisions. Inputs to medial and lateral
      SPFp were identified following injections of FG restricted to either division in
      male rats. The medial SPFp receives unique inputs from lumbar spinothalamic cells
      and brain regions involved in processing of visceral stimuli, supporting the
      hypothesis that the medial SPFp is involved in the relay of genitosensory
      information critical for the expression of male sexual behavior. The afferents of
      the lateral SPFp include brain regions involved in processing of visual and
      auditory signals and support a role for this subdivision in relay of visual and
      auditory information. Thus, the two subdivisions of SPFp are anatomically and
      functionally distinctive.

PMID- 12815753
TI  - Urocortin in the central nervous system of a primate (Cebus apella): sequencing,
      immunohistochemical, and hybridization histochemical characterization.
AB  - The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various
      regions of the nonprimate mammalian brain have been reported. However, the
      Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN
      expression is conserved across species. Although UCN peptides are present
      throughout vertebrate phylogeny, the functional roles of both UCN and EW remain
      poorly understood. Therefore, a study focused on UCN system organization in the
      primate brain is warranted. By using immunohistochemistry (single and double
      labeling) and in situ hybridization, we have characterized the organization of
      UCN-expressing cells and fibers in the central nervous system and pituitary of
      the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN
      was determined to establish the level of structural conservation relative to the
      human sequence. To understand the relationship of acetylcholine cells in the EW,
      a colocalization study comparing choline acetyltransferase (ChAT) and UCN was
      also performed. The cloned monkey prepro-UCN is 95% identical to the human
      preprohormone across the matched sequences. By using an antiserum raised against
      rat UCN and a probe generated from human cDNA, we found that the EW is the
      dominant site for UCN expression, although UCN mRNA is also expressed in spinal
      cord lamina IX. Labeled axons and terminals were distributed diffusely throughout
      many brain regions and along the length of the spinal cord. Of particular
      interest were UCN-immunoreactive inputs to the medial preoptic area, the
      paraventricular nucleus of the hypothalamus, the oral part of the spinal
      trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae
      VII and X. We found no UCN hybridization signal in the pituitary. In addition, we
      observed no colocalization between ChAT and UCN in EW neurons. Our results
      support the hypothesis that the UCN system might participate in the control of
      autonomic, endocrine, and sensorimotor functions in primates.

PMID- 12815755
TI  - Ultrastructural analysis of [3H]thymidine-labeled cells in the rat utricular
      macula.
AB  - Ototoxic drugs stimulate cell proliferation in adult rat vestibular sensory
      epithelia, as does the infusion of transforming growth factor alpha (TGFalpha)
      plus insulin. We sought to determine whether new hair cells can be regenerated by
      means of a mitotic pathway. Previously, studies have shown that the nuclei of
      some newly generated cells are located in the lumenal half of the sensory
      epithelium, suggesting that some may be newly generated sensory hair cells. The
      aim of this study was to examine the ultrastructural characteristics of newly
      proliferated cells after TGFalpha stimulation and/or aminoglycoside damage in the
      utricular sensory epithelium of the adult rat. The cell proliferation marker
      tritiated-thymidine was infused, with or without TGFalpha plus insulin, into the
      inner ears of normal or aminoglycoside-damaged rats for 3 or 7 days by means of
      osmotic pumps. Autoradiographic techniques and light microscopy were used to
      identify cells synthesizing DNA. Sections with labeled cells were re-embedded,
      processed for transmission electron microscopy, and the ultrastructural
      characteristics of the labeled cells were examined. The following five classes of
      tritiated-thymidine labeled cells were identified in the sensory epithelium: (1)
      labeled cells with synaptic specializations that appeared to be newly generated
      hair cells, (2) labeled supporting cells, (3) labeled leukocytes, (4) labeled
      cells that we have classified as "active cells" in that they are relatively
      nondescript but contain massive numbers of polyribosomes, and (5) labeled
      degenerating hair cells. These findings suggest that new hair cells can be
      generated in situ by means of a mitotic mechanism in the vestibular sensory
      epithelium of adult mammals.

PMID- 12815757
TI  - Nociceptor structural specialization in canine and rodent testicular "free" nerve
      endings.
AB  - The receptive fields (RFs) of polymodal nociceptor units of canine testis consist
      of small fascicles of branching axons ending as clusters within the thin vascular
      layer overlying the seminiferous tubules. This propitious arrangement enabled
      serial reconstruction of electron micrographs of a flat, punctate zone,
      identified during recording of impulse discharge of a single physiologically
      characterized nociceptor "unit." The RFs showed multiple axons, with some
      branching and sequential vesicle-containing swellings, similar to what have been
      called terminals and assumed to constitute impulse generating sites in other
      tissues. Consistent with this interpretation is the local presence of: (1)
      clusters of small mitochondria, (2) glycogen granules, and (3) sectors of
      axolemma denuded of Schwann cell processes and thus "free" endings directly
      contacting the epithelial basal lamina. The most distal sectors showed additional
      morphologic properties: (1) zones of vesicles embedded in an extensive granular
      matrix, (2) preterminal arrays of "axonal reticulum" derived from the smooth
      endoplasmic reticulum displacing axonal cytoskeletal elements, (3) a variety of
      sizes and electron lucency in clear, spherical vesicles and a few granular or
      dense-core vesicles, and (4) specialization in the last Schwann cell of the
      fascicle. These latter features may reflect differences in the specialized
      receptor mechanisms of nociceptors that are difficult to detect without extensive
      serial electron microscopic analysis. Alternatively, these features may
      constitute a regional specialization of the testis. The term free nerve ending is
      perhaps an insufficient and inaccurate descriptor of the morphology of
      nociceptors. These findings are considered in the context of their possible
      relation to the sensitized vanilloid receptor mechanism unique to nociceptors.

PMID- 12815758
TI  - Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion
      neurons of the rat, with special reference to coexpression.
AB  - Vesicular glutamate transporters are responsible for glutamate transport into
      synaptic vesicles. In the present study, we examined immunohistochemically the
      expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal
      ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated
      that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in
      their cell bodies. It also indicated that large and small trigeminal ganglion
      neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence
      histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons
      express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT
      expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon
      terminals in the superficial layers of the medullary dorsal horn also showed
      VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed
      to form the central core of the synaptic glomerulus. These results indicated that
      VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most
      trigeminal ganglion neurons.

PMID- 12815759
TI  - Neurotrophin-3 is expressed in a discrete subset of olfactory receptor neurons in
      the mouse.
AB  - In transgenic neurotrophin-3 lacZ-neo (NT-3(lacZneo)) mice, in which the coding
      region for NT-3 is replaced by Eschericia coli lacZ, the expression of beta
      galactosidase faithfully mimics the expression of NT-3 (Vigers AJ, Baquet ZC,
      Jones KR [2000], J Comp Neurol 416:398-416). During embryonic and early postnatal
      development, beta-galactosidase is detected in the olfactory system, beginning at
      embryonic day 11.5 in the nasal epithelium and at embryonic day 16.5 in the
      olfactory bulb. Levels of beta-galactosidase rise with age, reaching a peak
      during the second postnatal week, when beta-galactosidase reactivity is visible
      in up to 50% of the glomeruli. As the animal matures, the beta-galactosidase
      levels decline, but staining remains present in axons and cell bodies of a
      specific subset of olfactory receptor neurons (ORNs) projecting to a limited
      subset of glomeruli. The heavily labeled ORNs do not follow the typical OR
      expression zones in the epithelium but appear similar to the "patch" expression
      pattern of mOR37 receptors. The most heavily reactive glomeruli exhibit a
      striking reproducible pattern in the ventral olfactory bulb (OB). Some glomeruli
      of the OB contain calcitonin gene-related peptide (CGRP)-immunoreactive fibers of
      the trigeminal nerve. However, double-label immunocytochemistry for CGRP and beta
      galactosidase rendered no correlation between trigeminal innervation and the
      degree of innervation by NT-3-expressing ORNs. Thus, the timing and presence of
      beta-galactosidase in a subset of ORNs suggests that NT-3 plays a role in
      synaptogenesis and/or synapse function in a specific subset of ORNs within the
      olfactory bulb.

PMID- 12815760
TI  - [The role of specialist advisory boards in the development of anesthesiology and
      intensive care in Poland].
AB  - Specialists Advisory Board for the first time was funded of July 20th 1950,
      followed by the establishing country and share specialists. Advisory Board since
      the beginning is responsible for increasing medical knowledge and prophylactic.
      First country specialist was elected Mieczyslaw Justyna MD, PhD, in 1951. This
      period characterized different opinions between surgeons and anesthesiologists
      about the future development of specialty. In 1953 the new system of
      specialization was introduced. The full-qualified specialist was recognized after
      36 months of clinical work. In 1961 the new system of organization of
      anaesthetics departments was introduced for the whole country. This system still
      exists in practice. In 1963 the lower stage of specialists (share) was
      introduced. In 1972 anaesthesiology was established as a specialty consists of
      following tasks: anaesthesia, intensive therapy, pain treatment and
      resuscitation. Intensive therapy is responsible for maintaining the vital
      function, diagnosis and treatment of cause of life emergency state. Intensive
      therapy, and intensive care were recognizing separately.

PMID- 12815761
TI  - [Role of the anesthesiologist in perioperative medicine].
AB  - Perioperative medicine is a new approaches for quicker and better preparation all
      patients for surgery and postoperative treatment. Perioperative medicine should
      fulfilled following problems: a) Preoperative assessment, b) Postoperative pain
      treatment, c) Postoperative intensive therapy. Anaesthesiologists are interested
      in above problems, except prolonged preoperative treatment, which is normally
      provided by other specialists. Perioperative medicine needs a new approach for
      training new type of anaesthesiologists well prepared for new type of
      responsibility.

PMID- 12815762
TI  - [Anesthesiology consulting unit in perioperative medicine].
AB  - There is a demand, caused by increase of one-day surgery, surgery of high risk
      patients with coexisting diseases, and growing need for patient education, for
      such improvement of preoperative preparation, which will enable an optimalization
      in patient care. That became a special task of Preanesthetic Evaluation Clinic.
      The aim of the paper was to analyze activity of local Preanesthetic Evaluation
      Clinic in years 1993-2000. Special emphasize was put on: assessment of Clinic
      functioning, with regard to variety of consultations, perioperative patient
      education, use of perioperative risk scales, processing of guidelines of
      laboratory tests in particular groups of patients, assessment of perioperative
      fear factors. Analyze of consultations was conducted using custom design computer
      program, operated in the "Clinic since" 1997. Discussing own experiences, a
      necessity of patient education was emphasized as a significant factor lowering
      perioperative fear. There was also a presentation of perioperative risk
      assessment methods as well as guidelines of laboratory tests improving clinical
      effectiveness. Information for patients, prepared in the Clinic "What should you
      know about anesthesia" was described. As conclusions perspectives of further
      development of the Clinic were shown. Growing significance of an anesthetic nurse
      in perioperative patient preparation was foreseen. A demand for improving
      electronic patient records as well as use of new technologies was proven.

PMID- 12815763
TI  - [Preparation of the patient for reconstructive surgery of the abdominal aorta as
      an element in prevention of perioperative complications].
AB  - The tasks of an anesthetist in preoperative preparation of the patients submitted
      for reconstructive surgery of the abdominal aorta have been the subject of this
      paper. These tasks thought as an element of prevention of perioperative
      complications have been preceded by the description of characteristic of this
      steadily increasing population of patients with aortic abdominal aneurysm, or
      obliterative atheromatosis of the abdominal aorta (syndrome Leriche). There is a
      justified need for elective surgery in this population of patients because of the
      following premises: a substantial minor perioperative mortality (about 3% now) in
      the cases of aortic aneurysms, the steady high mortality in emergency operations
      and difficulty to foresee the dynamics in enlarging of aortic aneurysms, as well
      as the risk of their rupture. An elective surgery in Leriche syndrome decreases
      probability of splanchnic perioperative complications because of bowel ischaemia.
      Hypertension and ischaemic heart disease are detected in about 50% of described
      population and they comprise also the premises for perioperative complications in
      this group of patients. The risk of such a complications results also from
      clamping and declamping of the aorta, the necessary stages of aortic abdominal
      surgery. Characteristic pattern of described population and the pathomechanisms
      of perioperative complications call for precise and complex preoperative
      evaluation of these patients. Preoperative evaluation has been contemporary
      defined as a clinic of preoperative appraisal because of its importance. In
      elective procedures this clinic embraces two stages: prehospital and hospital. In
      both an anesthetist should play an integrative role in the activities of
      interdisciplinary team which prepares the patients for surgery. The peculiar task
      in this team belongs to the cardiologist, whose experience should also embrace
      the problems of surgical patients. The tasks of an anesthetic team in emergency
      concerning aortic surgery have been exposed in this paper. A proper understanding
      by anaesthetist of his/her role as an integrator of interdisciplinary team in
      perioperative stage of surgical disease is a new task for young doctors as well
      as for their teachers.

PMID- 12815764
TI  - [Qualification of patients for procedures to resect lung parenchyma during
      general anesthesia].
AB  - Authors described the methods and techniques of pulmonary and circulatory
      assessment of patients undergoing pulmonary resection. The most emphasis has been
      put on the perioperative management specially in patients with compromised
      pulmonary and circulatory system.

PMID- 12815765
TI  - [Point systems for evaluating coma in patients with injuries of the central
      nervous system (CNS)].
AB  - Paper reviews various coma scales which are used to monitor consciousness after
      sustaining severe injuries of CNS. Glasgow Coma Scale, at present the most
      frequently used, was compared to recently developed scales, which are more useful
      for monitoring persistent comas, allows to evaluate discrete changes in patient's
      state more precisely and to predict the outcome. The necessity of evoked
      potentials' measurements, such as Trigeminal-Auditory Glasgow (Coma Scale) has
      been stressed.

PMID- 12815766
TI  - [Psychological and sociologic requirements to prepare for anesthesia and surgery
      of patients with intracranial invasive processes].
AB  - Response to anxiety has been analyzed in 195 patients operated because of
      intracranial expansive process and influence of standard and individualized
      preoperative preparations over it.

PMID- 12815767
TI  - [Neurotrauma in treatment of nervous system injuries--principles in cooperating
      with anesthesiologists].
AB  - After brain trauma neuronal degeneration results due to the combination of
      primary mechanical disruption of CNS parenchyma and the secondary
      pathophysiological events. The fact that the treatment can modified the clinical
      course and the final outcome, implies that is indeed a modifiable secondary
      neurodegenerative process which is caused by the mechanical injury. Contemporary
      in patients with craniocerebral trauma and with polytrauma our management is
      focused on prevention of secondary brain injury. On the accident scene that is
      crucial to appropriate ventilate the patient, stabilize blood pressure and
      prevent shock. The diagnostic tool of choice is CT, but made in the very early
      stage could revealed false negative scan. That could be the cause of missed
      beginning of intracranial pressure increase in artificially ventilated patients.
      Multimodality monitoring in highly specialized centers could enable early
      detection of such increase (ICP) and help in estimation of indication for
      surgical treatment. The mechanism, direct sequelae of head trauma and
      neurological symptoms dynamics are also important.

PMID- 12815768
TI  - [Procedures for patients with brain injuries and GCS <8].
AB  - Epidemiologic date concerned to multiple injuries with concomitant brain injuries
      are presented. The basic mechanisms developing brain damage are pointed out and
      principles managing with patients for protection against secondary injuries. The
      necessity of treatment this kind of patients in intensive care centers with broad
      possibilities in monitoring and diagnostic equipment is defined.

PMID- 12815769
TI  - [Experiments in evaluation of brain oxygenation and metabolism based on
      continuous bilateral SjO2 monitoring and metabolic glucose transformations in
      patients after severe cranio-cerebral injuries].
AB  - The study group consisted of 17 patients after severe cranio-cerebral injuries-in
      GCS below 8. Saturation in both jugular bulbs was measured by using fiberoptic
      catheters, the concentration of lactate taken from jugular bulbs was measured
      too. These values were compared to concentration in peripheral arteries. All
      measurements were started within the first 24 h after trauma and lasted 5 days.
      Diagnosis of intracranial pathology was established by using CT, which was done
      directly after admission to the hospital. Interdependence between the state of
      patient in GOS and variability saturation and concentration of lactate was
      showed. Desaturation occurred before the neurological sings of intracranial
      hypertension what had influence on way of treatment and diagnostics. Bilateral
      measurement of the saturation is more useful to make diagnostic unilateral
      measurement.

PMID- 12815770
TI  - [Anesthesiology and day surgery].
AB  - The day surgery, known also as an office based practice, is a major change in the
      clinical medicine of the last two decades. In some countries (for instance in
      Austria) exists a clear difference between the ambulatory and the day surgery.
      While the ambulatory patient does not need a hospital bed at all, the day surgery
      patient occupies a bed for at least few hours, but never stays in the unit
      overnight. The shift from the hospital to extrahospital surgery is dictated by
      economical pressure on hospitals, are made possible by new non-invasive surgical
      techniques and new anaesthetic drugs and, finally, demanded by the society.
      Anaesthesiologists play a major role in this development, their main task in this
      new scenario is to secure a balance between the "fast track" approach ot the out
      patient surgery and the patient's safety. The meticulous application of the
      standards in monitoring and perioperative care is the primary obligation of an
      anaesthesiologists. There is no clear definition of the magnitude of the
      operation, which can be performed in the settings of day surgery, it varies
      according to organisation of such units and from the proximity of the hospital in
      its background. Generally from the day surgery programs should be excluded
      patients with the risk class above ASA 2, operations lasting more then 90
      minutes, all intracranial and intrathoracic operations and all procedures
      requiring blood transfusion. Day surgery is generally free from mortality and
      major complications like myocardial infarction, pulmonary embolism or
      neurological consequences, therefore the assessment of outcome should include
      minor morbidity, pain relief and satisfaction of the patient.

PMID- 12815771
TI  - [The influence of anesthesia methods on appearance of perioperative complications
      in patients after lung parenchyma resection].
AB  - We analyzed the influence of different methods of anaesthesia on perioperative
      complications in 184 patients (ASA 1 and 2) anaesthetized with intermittent one
      lung ventilation for pulmonary resection. Depends on the method of anaesthesia
      patients were divided into 3 groups: Group 1--patients under inhalation
      anaesthesia, Group 2--patients under mixed inhalation and intravenous anaesthesia
      and Group 3 patients anaesthetized intravenously. The analysis of intra- and
      postoperative data showed no correlation between perioperative complications and
      methods of anaesthesia, when the appropriate technique of anaesthesia has been
      used.

PMID- 12815772
TI  - [Reasons for optimizing perioperative anesthesia methods in neurosurgical
      patients--personal observations and innovations].
AB  - Own observations and experiments in neuroanaesthesia were presented, some of them
      controversial and in present day even historical, other put into practice for
      safety and comfort of patients and neurosurgical team.

PMID- 12815773
TI  - Arterial to end-tidal carbon dioxide difference during craniotomy in severely
      head-injured patients.
AB  - Clinical data suggest that cerebral blood flow (CBF) can be abnormally low within
      the first four to eight hours after severe head injury (SHI). An aggressive
      hyperventilation can additionally worsen CBF and provoke cerebral ischemia.
      Therefore an accurate PCO2 monitoring in SHI patients (pts) is necessary. PetCO2
      failed to reflect PaCO2 in SHI pts treated in neurosurgical ICU. Up to now, the
      validity of PetCO2 monitoring in estimating PaCO2 during an acute posttraumatic
      craniotomy has not been studied. Forty five adult SHI pts operated on because of
      an acute intracranial posttraumatic haematoma within 8 hours after head trauma
      entered the study. The standard anaesthetic protocol included N2O/O2, fentanyl
      and pancuronium bromide anaesthesia, and mechanical ventilation with respiratory
      rate 10 divided by 12 bpm and tidal volume in mL = body weight (kg) x 10 - 100.
      After obtaining a stable PetCO2 arterial blood sample was taken for PaCO2
      measurement and P(a-et)CO2 = PaCO2 - PetCO2 was calculated. P(a-et)CO2 ranged -9
      divided by 20 mm Hg (5 +/- 6; mean +/- SD). P(a-et)CO2 between 2 mm Hg and 6 mm
      Hg was found in 17 (38%) patients only. A negative P(a-et)CO2 was stated in 20%
      of patients. No relationships between P(a-et)CO2 and pts age and mean arterial
      pressure were found. P(a-et)CO2 was higher in normocapneic pts than in
      hyperventilated ones and tended to decrease with an increase in heart rate. We
      can conclude that during an acute craniotomy in SHI pts, PetCO2 does not reflect
      accurately PaCO2 and the monitoring of adequacy of ventilation should be based on
      repeated or continuous measurements of an arterial PCO2.

PMID- 12815774
TI  - [The effect of small doses of 7.5% NaCl on brain bulk during elective
      craniotomies].
AB  - In 16 patients (ASA I i II) aged 16-76 years (48 +/- 15; mean +/- SD) operated on
      because of intracranial expanding mass, the effect of hypertonic saline (7.5%--1
      ml/kg b.w.) on brain bulk (BB) was evaluated. Patients were anaesthetised with a
      slight hypocarbia (PaCO2 = 33.3 +/- 3.5 mmHg). BB was scored after opening the
      dura (T0) and 15 min. (T15) after hypertonic saline (HS) infusion. Five points BB
      scale was used. Brain bulk reduction (D BB) was calculated as a difference: BB15
      BB0. Tomographic signs of intracranial expansion (TSIE) in preoperative CT were
      scored using the scale from 5 to 15 points assessing (1 to 3 points) the size of
      mass lesion, the size of perifocal oedema, midline shift, displacement of
      ventricles and basal cisterns compression. Systolic (SBP), diastolic (DBP) blood
      pressures and heart rate (HR) were monitored. Serum natrium (SNa), kalium (SK)
      and osmolarity (Sosm) were measured at T0, T15 and Tp0 (one hour after
      operation). Student's t-test, Wilcoxon test and Spearman correlation were used
      for statistical analysis. P < 0.05 was considered as statistically significant.
      HS caused significant decrease in BB (p = 0.002). In 12 patients with a solid
      brain tumor a negative correlation between BB and TSIE was found (r = -0.68). A
      slight but significant decreases in SBP and DBP at Tp0 and T15 as well as
      decrease in HR due to HS were stated. SNa and Sosm increased at T15 and reminded
      elevated at Tpo. We can conclude that 7.5% saline in a dose of 1 ml/kg b.w.
      reduces brain bulk during craniotomy in patients with supratentorial mass
      lesions. In patients with a solid brain tumor this effect correlates negatively
      with a size of expanding mass. A slight changes in blood pressure and heart rate
      due to HS as well as moderate decrease in SK are within limits of clinical
      acceptance.

PMID- 12815775
TI  - [Effect of general anesthesia induction on cerebral circulation in subacute and
      chronic subdural hematoma assesssed by computerized rheo-encephalography].
AB  - Cerebral circulation in 21 patients with subacute (SSH) and chronic subdural
      hematoma (CSH) were studied by computerized rheoencephalography before and after
      induction of general anesthesia. ECG and REG courses were sampled with a
      frequency of 62.5 Hz during a period of 15 minutes, and both sets of data points
      were fitted by an cubic polynomials. We introduced the classification of the REG
      pulse related waveform (PRW) according to the number of the inflection points in
      the anacrotic branch. The cases of normal pulse form, with almost vertical
      systolic upstroke corresponded with only one inflection point in the ascending
      branch (grade I). We assumed that the presence of three or greater number of
      inflection points reflected more gradual systolic rise, is characteristic for
      regressive changes of the arterial wall (grade II). The relative duration of the
      anacrotic branch was calculated. The first obtained result was the significant
      correlation between REG and clinical status. The unfavorable effect of induction
      on cerebral circulation corresponded with less favorable results of treatment.
      Our preliminary results indicate the clinical value of REG examination in the
      preoperative evaluation of the cerebral circulation.

PMID- 12815776
TI  - [Perioperative sedation and analgesia for complications from arthroscopy and
      arthrotomy of the knee joint].
AB  - Estimation of the quality of the epidural anaesthesia of the patients sedated
      with Alprazolam and Midazolam in premedication before arthroscopy or arthrotomy
      of the knee was the goal of our study. Forty six (34 men and 12 women) ASA
      physical status 1-2 patients were divided into groups depending on the drugs
      orally applied in premedication (Alprazolam 0.5 mg, n = 29 or Midazolam 15 mg, n
      = 17) and of the kind of analgesia. The patients subjected to arthroscopy were
      treated with a single-shot epidural analgesia (n = 38), while those subjected to
      arthrotomy--with a continuous epidural analgesia (n = 8). 2% Lignocain with
      addition of Epinephrine and Fentanyl was used in the perioperative analgesia,
      while 0.25% Bupivacain with addition of Morphine was used in the postoperative
      period when continuous epidural analgesia was applied. The ISAS, VAS and Ramsey
      scales were used and the data were analysed with the Kormogolov test. The
      perioperative sedation in arthroscopy and arthrotomy of the knee is good without
      any significant differences associated with a kind of the drugs applied. The
      single-shot epidural anaesthesia is inadequate only during a prolonged
      arthroscopy of the knee. The postoperative continuous epidural analgesia,
      expressed in the VAS scale, was inadequate. A level of general satisfaction of
      the patients of the sedation and analgesia, expressed in the points of the ISAS
      scale, was satisfactorily good.

PMID- 12815777
TI  - [Mivacurium--use for complications of facial-cranial surgery--personal
      experience].
AB  - The aim of this study was to evaluate the effectiveness of mivacurium (Mivacron-
      GlaxoWellcome) during combined general anaesthesia in the operations on the
      facial cranium, after tracheal intubation performed using suxamethonium chloride
      (Chlorsuccillin--Polfa PL). We examined 20 patients, 17-65 years old, who were
      underwent operations due to facial and neck neoplasms or trauma. Patients were
      divided into two 10-person groups. In first group the dose of Mivacron for the
      induction of anaesthesia was 0.15 mg/kg of body weight, in second group the dose
      was 0.1 mg/kg of body weight. Next doses used during maintenance of anaesthesia
      were 0.1 mg/kg of body weight in both groups. Metohexital, fentanyl, nitrous
      oxide and oxygen were used for the maintenance of anaesthesia. The level of
      neuromuscular block was estimated using Ministim MS IIIA instrument. The mean
      time to maintain 95-99% neuromuscular block after inductive dose 0.15 mg/kg
      Mivacron was 15 minutes 26 seconds, and after the dose of 0.1 mg/kg--13 minutes
      55 seconds. The time from the injection of the drug to maintain neuromuscular
      block was 1 minute 52 seconds and 1 minute 50 seconds, respectively. We did not
      observe neither negative influence of drug on the cardiovascular system nor the
      reactions of histamine release. Injection of suxamethonium chloride before the
      tracheal intubation did not prolong the time of Mivacron activity.
      Anticholinesterase agents was not use in any case. By 4 patient with heart
      failure prolongation of the activity time of Mivacurium was observed. The dose of
      0.1 mg/kg, is efficient to maintain of the neuromuscular block on the stabile
      level. This allows the reduction of the total dose, and the decrease of the costs
      of the operation.

PMID- 12815778
TI  - [Presence of the trace elements from carbon dioxide absorbent containing lime
      using a circular apparatus during general anesthesia. ].
AB  - The aim of the study was to evaluate release of the trace elements from carbon
      dioxide absorbent containing soda lime during general anesthesia. We compared two
      suppliers Polish "Polfa" and German "Drager". Following trace elements were
      evaluated: chromium, copper, zinc, cadmium, lead, nickel in soda lime. In blood
      of the patients we evaluated: copper, zinc, lead, cadmium, bromine, rubidium,
      iron, mercury. Proton Induced X-ray Emission (PIXE) was used to measure
      concentrations of the elements. Probes of soda lime were analyzed before
      anesthesia (Polfa, Drager), 6 hr after the use (Polfa only) and after 10 weeks
      (Drager only). 10 patients were divided in two equal groups, one was anesthetized
      using soda lime from Polfa and another one from Drager. Blood samples were taken
      before anesthesia, immediately after and the next day. Mean values of the
      concentrations of the elements in soda lime coming from Polfa ranged from 0.20
      ppm (nickel) to 7.19 ppm (zinc). In Drager the measurements were from 0.22 ppm
      (nickel) to 3.70 ppm (zinc). Mean concentrations of trace elements in blood
      samples were between 0.20 ppm (lead) and 487 ppm (iron) for the patients
      anesthetized with Polfa soda lime. In Drager the measurements ranged from 0.15
      ppm (lead) to 485 ppm (iron). Concentrations of cadmium and mercury were below
      the method's limit. Mean values were almost the same in all time points.
      Statistical analysis was done using paired t-tests. Values of P < 0.05 were
      consider significant. We concluded that there were no statistically significant
      differences between examined groups. Thus, we can say that trace elements were
      not released from soda lime and concentrations of examined elements in patients'
      blood were not affected by general anesthesia.

PMID- 12815779
TI  - [Principles of qualifying children for planned surgical procedures].
AB  - Children are prone to greater preoperative stress and more frequent accidents
      during anaesthesia. To reduce stress--a preoperative visit, information for child
      and parents, premedication and parental presence during induction of anaesthesia
      have all been successfully used. Surgery can often be performed as a "day case",
      there is no need for longer than 6 hour fasting (2-3 hours in infants and after
      fluids only) before induction of anaesthesia, and needle sticks are often avoided
      before the child loses consciousness. Laboratory tests are also not needed in
      children with good general health status planned for minor procedures. There is
      less emphasis on minimal hemoglobin level of 10 g/dl, the physician assessment of
      circulatory status is preferred rather than stiff laboratory values. Less stress
      for children means also less problems during induction and recovery as well as
      less need for prolonged postoperative care.

PMID- 12815780
TI  - [Anesthesia-related and surgical problems in day neurosurgery in children].
AB  - Problems resulted from necessity of securing safety for 4500 children with
      intracranial congenital hydrocephalus and subdural hygromas diagnosed and
      operated in one-day neurosurgery terms.

PMID- 12815781
TI  - [Sevofluran in pediatric practice--personal experience].
AB  - Sevofluran a new inhalational anesthetic is a preferred anesthetic agent for
      induction and maintenance of pediatric anesthesia because of its rapid induction,
      recovery characteristics and acceptable cardiovascular profile--now also
      accessible in Poland. Sevofluran isn't an ideal anesthetic, and the issue of
      postoperative excitement, potential nephrotoxicity requires clarification. This
      study was designed to compare the emergence characteristics of sevoflurane with
      halotane anaesthesia in paediatric patients having various surgical intervention.
      102 children divided for subgroup of premedicated and nonpremedicated, underwent
      inhalation induction with nitrous oxide/oxygen and sevofluran or halotane.
      Incremental doses of either study drug were added until loss of eyelash reflex
      was achieved. We didn't use higher concentrations of sevoflurane than 5.5 Vol%
      and 3.5 Vol% for halothane. Sevoflurane patients has a greater incidence of
      emergence agitation.

PMID- 12815782
TI  - [Patient satisfaction with anesthesia as a measure of quality of anesthesia
      care].
AB  - Patient satisfaction with anaesthesia is very important as a expectancy
      satisfaction in perioperative care. It is simultaneously patient opinion about
      the anaesthetic care prior to and during anaesthesia, and shortly after the
      operation. The aim of the research was to evaluate the patient satisfaction and
      to determine the factors connected with satisfaction in the perioperative period
      Out of a total of 250 patients, 155 women (62%) and 95 men (48%) underwent
      general and local anaesthesia due to the operations. They answer 55 questions on
      the third day after the operation. At the same time anaesthesiologists and nurses
      evaluate the quality of theirselves anaesthesia. In the opinion of anaesthetic
      team the quality of anaesthesia was very good--51.6%, good--46.8% and adequate
      only 2.6%. Positive opinion about the quality of anaesthesia expressed 87% of
      patients, negative only 0.5% and 12.5% have no opinion. The very good atmosphere
      was in Preanaesthetic Evaluation Clinic and during the admission to the operating
      room. The factors decreased patient satisfaction immediately after the operation
      were breathing difficulties, vomiting, nausea, feeling coldness and pain. The
      main factors evaluating the quality of anaesthetic care and patient satisfaction
      are specific information, proper premedication and feeling safety in the
      operating room. On the other hand the discomfort and insufficient analgesia
      decreased patient satisfaction with anaesthesia.

PMID- 12815783
TI  - [Prognostic evaluation of results after intensive therapy based on APACHE III in
      surgical and non-surgical patients].
AB  - The objective of the presented studies was the assessment of survival and death
      prediction by APACHE III system in surgical and non-surgical patients treated in
      an intensive therapy unit. The investigated group included 410 patients examined
      by the APACHE III during the first 24 hours after admission to the multiprofile
      ITU in the years 1995-1997. The APACHE III system was used on the basis of an
      agreement with the APACHE Medical System INC. The clinical value of the applied
      system was assessed by the statistics of logistic regression. In the group of 410
      ITU patients, 263 (64.1%) survived and 147 (35.9%) died. The death rate in the
      surgical group was 27.3%. The major non-surgical group (333--81.2%) showed a
      death rate of 37.8%. The precision of predictions on the basis of APACHE III was
      75.9% with the assumption that the probability of death risk in each patient was
      0.5 and more. For the whole studied group system showed an area under ROC equal
      to 0.830 in 95% of the confidence interval. In the group of surgical patients,
      the APACHE III system showed a goodness of fit on the basis of Hosmer's and
      Lemenshow's test and the highest total percentage (81.8%) of correct
      classification and high value of the ROC = 0.868. The APACHE III system is a good
      and correct outcome prediction tool for adult patients in a multiprofile ITU. The
      comparison of the surgical and non-surgical groups of patients showed a better
      agreement and correctness of the intensive therapy outcomes predictions in the
      surgical group.

PMID- 12815784
TI  - [Problems with infections during the perioperative period].
AB  - The paper addresses issues related to the prophylactic and empirical use of
      antibiotics in surgery. Apart from the factors related to post-operation
      infections, it presents recommendations and proposals for the prophylactic use of
      antibiotics in particular types of operations. The recommendations are based on
      the American and European specialist literature, with the differences between
      these two approaches clearly outlined. Additional comments are provided for the
      important elements of prophylactics in particular types of operations. In the
      part concerning the use of antibiotics in treatment of intra-abdominal
      infections, the focus is on the general rules for antibiotherapy in pancreatitis.
      There is also a discussion of mycotic complications accompanying intra-abdominal
      infections. The paper ends with specific indications for the empirical use of
      antibiotics in intra-abdominal infections.

PMID- 12815785
TI  - [Morphine--myths and facts].
AB  - Morphine in the form of opium tincture accompanies the mankind for several
      thousands years. At the beginning of the twentieth century morphine has been
      isolated from opium and it was used initially to treat ... opium addicts. At
      present it plays an important role in the treatment of severe pain of different
      origins and (more seldom) in the premedication for general anaesthesia. Despite
      its side effects it is irreplaceable especially in the treatment of cancer pain.
      Nowadays the chronic use of oral morphine preparations has been supported by
      medical authorities who at the same time warn against incorrect dosage and
      combination with other drugs. Many clinical data concerning oral morphine show
      that it is safe and effective even in the patients with advanced cancer and poor
      performance status. Our paper lists myths and common mistakes connected with
      morphine use and confronts them with well established facts confirming its
      effectiveness in cancer pain treatment.

PMID- 12815786
TI  - [Does intravenous administration of magnesium have an effect on postoperative
      analgesia?].
AB  - The study involved 67 patients operated for malignant tumours of stomach and of
      the colon. The patients have been divided into 3 groups: the NORMO group--20
      patients in whom the serum magnesium level remained normal during the whole
      period studied; the HYPO group--22 patients who developed hypomagnesaemia in the
      postoperative course; the MAG i.v. group--25 patients who on the day of surgery
      and on 4 days following surgery, received intravenously daily doses of 2.5 ml of
      20% MgSO4 per each 500 ml of transfused fluids. In all patients, the basic
      analgesic used was morphine, administered intramusculary or extraduraly. In the
      intervals between the doses of morphine, patients received intravenous doses of
      noramidopirine. In all three groups, the daily amounts of morphine and
      noramidopirine received by patients was the same. The intravenous administration
      of daily doses of 8 to 14 mmol magnesium in the postoperative period does not
      affect the amount of analgesics given to patients.

PMID- 12815787
TI  - [Levels of troponin I, tropoinin T, isoenzyme MB creatine kinase and myoglobins
      in blood serum for perioperative diagnosis of myocardial infarction in patients
      after coronary artery bypass graft surgery with extracorporeal circulation].
AB  - We studied plasma levels of troponin I (cTnI), troponin T (cTnT), creatine kinase
      MB (CKMBmass) and myoglobin (MB) in patients undergoing coronary artery bypass
      surgery with extracorporeal circulation and cardioplegia. In group 1 (25 patients
      without perioperative myocardial infarction) plasma levels of all markers studied
      were elevated after operation. In group 2 (24 patients with perioperative
      myocardial infarction) plasma concentrations of all markers exceeded several
      times levels observed in patients without myocardial infarction with maximal
      value for MB at 12 hours after operation; for cTnI and CKMBmass at 16 hours after
      surgery and for cTnT at 32 hours after the end of operation. ROC curves show cut
      off value for CKMBmass 20.3 ng/ml (sensitivity 79% and specificity 89%); for cTnI
      cut-off value was 0.8 ng/ml (sensitivity 80% and specificity 94%) for cTnT the
      cut-off value was 0.41 ng/ml (sensitivity 86% and specificity 88%) and for MB the
      cut-off value was 419 ng/ml (sensitivity 85% and specificity 70%). CONCLUSION:
      All markers studied are reliable biochemical tests for perioperative myocardial
      infarction, however, the analysis of ROC curves suggested that cTnI and cTnT
      might be more useful for diagnosis of perioperative myocardial infarction after
      conventional coronary artery bypass surgery.

PMID- 12815788
TI  - [The role of infusion fluids and blood derived preparations during the
      perioperative period].
AB  - The treatment with infusion fluids in perioperative period is a basic therapeutic
      method. Depending on clinical situation, the doctor has various fluids available,
      both blood-replacing, and blood-derived. The number of crystaloid and colloidal
      fluids used has been systematically growing in two last decades. Ever more
      importance, beside the 0.9% NaCl solution and Ringer's solution used, is gaining
      7.5% NaCl solution and hydroxyethyl starch solutions. The production of
      hydroxyethyl starch solutions in Poland has created an alternative to the use of
      dextran and gelatin solutions. The change towards treatment with blood components
      has caused the change of the strategy of therapeutic management of patients used
      as yet. For compensation of oxygen demand during blood loss, erythrocyte
      concentrate is commonly used. Such management requires blood-clotting factor
      monitoring. Hypofibrinogenaemia develops earlier than deficiencies of the
      remaining blood-clotting factors and later than thrombocytopenia. The use of
      fresh frozen plasma (FFP) is the first step in the treatment of pathological
      bleeding in surgically treated patients. The occurrence of thrombocytopenia shows
      great individual variability. Thrombocyte concentrate transfusion should be
      performed after laboratory determination of thrombocyte count.

PMID- 12815789
TI  - Evaluation on the effectiveness of perioperative nutritional therapy.
AB  - In the last three decade very important advances in venous access, enteral
      feeding techniques and parenteral and enteral nutrient formulations have made it
      possible to provide sufficient nutritional support to almost all patients. The
      clinical nutritional therapy became a progressive medical subspecialty. Despite
      the widespread use of nutritional management of different patient groups, many
      fields of nutritional support remain controversial. The critical review of the
      current medical literature is necessary evaluating the effectiveness of
      nutritional support in the perioperative period. This document represents a
      critical review of the available literature and contains suggestions,
      recommendations for the clinical practice. The historical background and
      development of perioperative artificial nutritional therapy are cited. Whenever
      possible, prospective randomised clinical trials (PRCTs) are evaluated because
      this is the most reliable method for evaluating clinical efficacy of a treatment.
      The incidence of postoperative complications, the length of postoperative
      hospitalisation and the mortality are considered good general indicator of
      effectiveness of perioperative nutritional therapy.

PMID- 12815790
TI  - [Therapeutic plasma exchange with particular regard to the perioperative period].
AB  - The end of the last decade of the XXth century caused that therapeutic plasma
      exchanges have found an important place in the therapeutic management of many
      pathological conditions. This was possible owing to the knowledge of the
      pathophysiology of many diseases and pathological factors present in circulation.
      Therapeutic plasma exchange is the procedure during which pathological substances
      are removed from patient's circulation without causing anaemia and oncotic
      pressure disturbances. The procedures are carried out in order to eliminate
      pathological components of the plasma. Therefore, the general indication to
      plasma exchange are disease entities, the pathogenesis of which depends on plasma
      composition abnormalities. The understanding of the mechanisms of action of
      therapeutic plasma exchange, pathogenesis of certain diseases, and results of
      controlled studies of procedure effectiveness made possible to establish the
      indications to the procedure. In view of varying indications to therapeutic
      plasma exchange, in the paper these indications are discussed which are of
      importance in perioperative period. In clinical practice, therapeutic plasma
      exchange in myasthenia gravis has been applied, among other, in acute states in
      order to stabilize patient's condition after thymectomy or during preparation for
      thymectomy. The resistance occurring to preparations of blood-clotting factors is
      the cause of their ineffectiveness in control of bleeding. Application of plasma
      exchange and removal of antibodies make possible to achieve sensitivity of
      patient's organisms to exogenous blood-clotting factors. Good effects were
      observed in the treatment of hepatic coma in which application of the procedures
      frequently enables survival until performing transplantation. Therapeutic plasma
      exchange is the method of symptomatic treatment. The procedures may enable or
      facilitate management of patients in preoperative or postoperative periods but
      they cannot cause permanent cure.

PMID- 12815791
TI  - [Clinical evaluation of hemofiltration in perioperative medicine].
AB  - Haemofiltration (HF) in perioperative period is used in order to improve the
      function of circulatory system by means of: elimination of cytokines in patients
      with increased inflammatory cascade activation; improvement of gas exchange
      conditions by decreasing the amount of lungs extravascular fluid; reduction of
      high levels of metabolism products; compensation of electrolyte disequilibrium
      and decreasing of right ventricle afterload as well as right and left ventricles
      preload. The aim of the study was clinical evaluation of usefulness of continuous
      vein-to-vein haemofiltration (CVVH) technique used in multiprofile adults
      intensive care. The analysis included 20 patients aged 24-73 (mean age 48.5),
      treated with HF in 1998-1999. HF was introduced in the following clinical
      conditions: multiorgan trauma with ARDS, acute pancreatitis with multiple organ
      dysfunction syndrome (MODS), peritonitis, status after laparotomy and chronic
      circulatory failure in patients qualified to heart transplantation. In six
      patients (30%), significant improvement of general state and stabilisation of
      haemodynamic and ventilation parameters were obtained. In fourteen patients
      (70%), despite CVVH, no improvement of circulatory and respiratory systems state
      was obtained. HF is very useful technique employed in perioperative medicine. It
      enables improvement of gas exchange conditions by decreasing the amount of lungs
      extravascular fluid in patients with ARDS in the course of MODS. HF simplyfies
      preparation the patient with chronic circulatory failure for diagnostic and
      therapeutic cardiosurgical procedures. In the course of sepsis and septic shock,
      HF creates better prospects to nutritional therapy and replaces haemodialysis or
      is its continuation.

PMID- 12815792
TI  - [Selected ethical problems of oncologic patients during the terminal period].
AB  - Patient suffering from terminal disease is depended on his environment more than
      any other one. He often suffers from nervous break down, anxiety and fear and he
      is usually unprotected from the environment. Fast development of medical science
      and its technicisation can lead towards dehumanization and lack of psychological
      and spiritual care, which should be based on clear ethical principles. Main lines
      of ethical principles of Health Service which are included in Deontological Code
      of Physicians and Collection of ethical principles for a qualified nurse are the
      main rules how to proceed as to fulfill the rule: "benefit of a patient is the
      superior law." According to its speciality Palliative Medicine introduces also
      four general ethical principles: 1. Patient will is a rule of treatment. 2. The
      principle of proportion--benefits from the treatment should be higher than losses
      and suffering from iatrogenic acting. 3. The principle of equality--stop taking a
      cure does not differ from not undertaking treatment. 4. The principle of
      relativity--life is not an absolute good, death is not an absolute evil. Holistic
      acts of Palliative Medicine determines also specific ethical attitudes,
      especially in the following: 1. Communication between a therapist and a patient
      and his family (interpersonal attitudes). 2. Procedures how to lessen suffering
      and its interpretation according to culture, tradition and religion ("nonsense
      and significance of suffering"). 3. Negation of euthanasia. 4. Spiritual,
      psychological and social care of patients.

PMID- 12815793
TI  - Fluctuations of gastrin, motilin and total bile acid levels in porcine blood
      before and after feeding.
AB  - In four young healthy pigs, the radioimmunological determinations of serum
      gastrin, plasma motilin and total serum bile acids were performed during four
      hours of the interdigestive state and up to one hour after standard feeding
      procedure. In 24-hr fasted animals, gastrin, motilin and bile acid concentrations
      fluctuated and duration of oscillation periods was similar to the length of the
      interdigestive motor cycle. However, only motilin peaks were temporally
      correlated with bile acid peaks. Feeding did not abolish motilin and bile acid
      fluctuations and significantly decreased serum bile acid level. It is concluded
      that the relationships among gastrin, motilin and bile acids are in part
      different in pigs from those in man and dog and still some controversy exists as
      to the regulatory role of both hormones mainly in the postprandial state.

PMID- 12815794
TI  - Interdigestive contractions of the gallbladder in rabbits: the real time
      ultrasonographical studies.
AB  - There are no reports concerning the ultrasonographical examination of gallbladder
      contractility in rabbits. Thus, the aim of this study was to assess the dynamics
      of gallbladder contractions in 7 rabbits. Animals were fasted 24 h before the
      experiments lasting 3-5 h. Ultrasonographical examinations were performed every
      10 min using USG 220 SLC machine. The sectorial ultrasound 3.5 MHz was placed in
      the right subcostal region. The maximal longitudinal gallbladder scans were
      obtained and the gallbladder volume was estimated using 3 methods. The highest
      values were obtained with the method approximating the gallbladder shape to
      ellipsoid. The second method approximating gallbladder shape to the barrel
      provided intermediate results and the lowest results were obtained with the sum
      of-cylinders method. The overall mean of interdigestive gallbladder volume using
      the latter method was 1.34 +/- 0.10 ml. Peak and interpeak values were 2.23 +/-
      0.33 and 0.99 +/- 0.18 ml, respectively, p < 0.01. The mean peak distance was
      69.6 +/- 7.4 min approximately remaining in concert with the reported MMC
      intervals in rabbits. It is concluded that the rabbit model for gallbladder
      ultrasonography may be useful for the study of gallbladder dynamics.

PMID- 12815795
TI  - [Evaluation of intersitial cells of Cajal (ICC) in the large intestine of
      humans].
AB  - Interstitial Cells of Cajal (ICC) are the pacemaker cells of the smooth muscle of
      the gastrointestinal (GI) tract. They are binding these muscle with the enterous
      nervous system and play an important role in the regulation of motility of the GI
      tract. Disturbiud in activity of those cells were observed in many functional
      diseases of the GI tract. The aim of this study was to evaluate the localization
      and morphological differences of the ICC between some region of the human colon.
      In this work we have performed the immunohistochemical method, using the
      monoclonal and policlonal specific antibodies against c-kit receptor (CD117) in
      paraffin embedded block. We find the ICC in the wall of colon in the muscle
      layers, mainly localized in the region of the myenteric plexus. No difference of
      the ICC between other region of the colon were observed in our specimen. In some
      cases of patients with diverticulosis we have observed less of ICC according to
      the control group. It's only early result, but let us know, that ICC play an
      important role in the pathogenesis of the motility disturbances of the GI tract.

PMID- 12815796
TI  - [Electrogastrography and manometry of the stomach in patients with disturbances
      of basic electrical rhythm].
AB  - Electrogastrography (EGG) is the only non-invasive method for investigating the
      myoelectric activity of the stomach. The aim was to show the relations occurring
      between the electromyographic and manometric recordings during the normal and
      abnormal EGG rhythm. A simultaneous EGG recording and manometry were performed in
      20 healthy people, in 26 patients with bradygastria (group I) and 21 with
      tachygastria (group II). In the control group, over 90% of the EGG recording time
      was in the range of normogastria. After a meal, there were observed a more than
      twofold increase in the EGG amplitude, an improvement in the recording stability
      with decrease in the dysarrhythmia percent, an increase in dominant frequency
      (DF) and a lowering in dominant frequency instability coefficient (DFIC). In
      groups I and II there was shown a considerable difference in the DF range, an
      increase in DFIC and the number of dysarrhythmia cases, the lack of correct
      increase in the amplitude and lowering in the average frequency of phasic
      contractions and motor indices (MI). Additionally in this group there was a fall
      in the amplitude of contractions without MMC, and this corroborates with weak
      contractile activity. There was a positive correlation between the EGG amplitude
      changes and amplitude of phasic contractions and MI and power ratios (PR) only in
      the phases I and II MMC. It suggests a relationship between the EGG amplitude and
      changes in the stomach position and its contraction activity. The lack of
      correlation between the average EGG frequencies of phasic contractions and the DF
      and DFIC values does not allowed to observe correlation between the frequency of
      the phasic contractions and EGG dominant frequency.

PMID- 12815797
TI  - The usefulness of low-pressure pneumoperitoneum in laparoscopic surgery.
AB  - The aim of the study was to assess the usefulness of low-pressure
      pneumoperitoneum (LP) in laparoscopic surgery. A consecutive group of 152
      patients qualified for laparoscopic cholecystectomy (LC) was assessed as to the
      possibility of performing the procedure with LP 7 mmHg. The following exclusion
      criteria were used: Body Mass Index (BMI) > 27 and laparotomy in medical history.
      The subsequent stage of the trial included 82 (53.9%) patients (73 females, 9
      males) meeting the inclusion criteria. The mean BMI was 25.23 +/- 1.4; mean age
      was 46 +/- 7.8 years. All the patients suffered from symptomatic uncomplicated
      gallstones confirmed in ultrasound. The pneumoperitoneum was created in a blind
      way with a Veress needle up to pressure of 12 mmHg and the first 10 mm TERNAMIAN
      EndoTip trocar was introduced under direct visual control. After the placement of
      other trocars, the working pressure was reduced from 12 mmHg to 7 mmHg. The pCO2
      concentration was monitored intraoperatively by a capnometer. Among 82 patients
      included into the study the LPLC was successfully performed in 73 (89%) patients.
      In 8 (9.75%) patients the working pressure had to be increased to 15 mm Hg due to
      the gallbladder exceeding 12 cm in length and difficulties in its proper
      mobilization required to visualize the neck of the gallbladder. All these
      patients were male and 3 of them were 55 years of age or more. In 1 (1.22%)
      patient conversion was necessary because of difficulties in identification of
      anatomical structures within the Calot's triangle. LC can be performed with a use
      of the LP technique in the majority of patients with BMI < 27 and no previous
      history of laparotomy. Gallbladder assessed in preoperative ultrasound as longer
      than 12 cm as well as male sex and age over 55 years indicate a higher risk of
      failure of the 4-trocar LPLC technique.

PMID- 12815798
TI  - Influence of different pressures of pneumoperitoneum on the autonomic system
      function during laparoscopy.
AB  - The effects of different pressure values of pneumoperitoneum on the activity of
      the autonomic nervous system (ANS) have not been investigated in detail. In this
      prospective study, 20 patients qualified for laparoscopic cholecystectomy were
      randomised to either low-pressure (LP = 7 mmHg) or standard-pressure (SP = 12
      mmHg) pneumoperitoneum groups, 10 patients each. The anesthesia was induced with
      fentanyl and thiopental and maintained with isoflurane. Ventilation was
      mechanically controlled (18 breaths per minute, end-tidal CO2 30-35 mmHg, instant
      capnometer monitoring). Intraabdominal pressure was maintained automatically by a
      CO2 insufflator. Patient were kept in a horizontal position. The ANS was
      evaluated by heart rate variability (HRV) analysis (POSTER ECG 2002 System)
      measured intraoperatively in three recordings of 5 minutes each: in awake
      patient, after induction of general anesthesia, and after creation of
      pneumoperitoneum. Power spectral analysis of HRV was applied, the low-frequency
      (LF = 0.05-0.15 Hz) and high frequency (HF = 0.15-0.45 Hz) spectral density of
      the HRV were analysed using the Fast Fourier Transform algorithm. The appropriate
      statistical analysis of data was performed. LF density decreased at the
      anesthetized stage and increased at the insufflated stage in both groups (p <
      0.01). LP resulted in lower sympathetic activation than SP pneumoperitoneum (LF:
      68.12 +/- 6.56 nu vs. 78.26 +/- 5.43 nu, p < 0.01; HF: 24 +/- 2.48 nu vs. 15.56
      +/- 2.54 nu, p < 0.05). IN CONCLUSION: pneumoperitoneum leads to sympathetic
      activation of the ANS. LP in comparison to SP pneumoperitoneum with carbon
      dioxide results in significantly decreased sympathetic activation during
      laparoscopy.

PMID- 12815799
TI  - [Early diagnosis of orthostatic hypotension in idopathic Parkinson's disease].
AB  - Autonomic dysfunction in idiopathic Parkinson's disease (IPD) is common and
      occurs in 70% of patients. The aim of the study was to evaluate autonomic
      mechanisms regulating cardiovascular system during tilt up test in IPD patients.
      The examination was performed in 35 patients with IPD (26 male and 9 female, mean
      age 60 +/- 9) and matched with gender and age 35 controls subjects (healthy
      volunteers, mean age 59 +/- 9). Patients were divided into two groups: group I-
      early stage of disease (n = 20) and group II--advanced stage of the disease (n =
      15). The tilt test in IPD patients and in the control group lasted 3 minutes. In
      both groups tilt test was performed with a head-up tilt position of 60 degrees
      (tilt table Manumed, Netherlands). In both groups 30:15 ratio were lower than in
      the control group 1.03 +/- 0.08, 0.97 +/- 0.09 v 1.23 +/- 0.1 respectively (p =
      0.001). In the second group the heart-rate variability after the tilt test was
      lower 6.2 +/- 4/min than in the control group 10.2 +/- +/- 1.9/min and group I
      8.8 +/- 4/min (p = 0.01). The decrease of the systolic pressure in response to
      the tilt test was the highest in group II (16 +/- 14 mmHg), in the control group
      4 +/- 7 mmHg, in group I 13 +/- 11 mmHg (p = 0.001). Ortostatic hypotension in
      IPD occurs in 36% of patients in an early stage and in 47% of patients in an
      advanced stage of the disease. The use of the tilt test enables the early
      diagnosis of cardiovascular disturbances in IPD.

PMID- 12815800
TI  - Various patterns of oral mucosa candidiasis treatment in HIV patients.
AB  - Oral cavity is the site of numerous HIV infection manifestations. Oral mucosa
      candidiasis is the most common one. It may be the earliest sign of the underlying
      disease. Long lasting observations give evidence that antiretroviral therapy is
      beneficial also in the cases of this opportunistic infection because it reduces
      both the number and severity of relapses, however, the prolongation of the
      patients' survival time creates the need of antifungal therapy prolongation, and
      thorough observation of its effectiveness and methods. We decided to analyze the
      influence of antiretroviral therapy with at least three drugs on the development
      of oral mucosa candidiasis in the out- and inpatients of the Jagiellonian
      University Medical College Clinic of Infectious Diseases (or Outpatient Clinic)
      in Cracow. The study was carried out in 75 patients with confirmed HIV infection.
      We have shown a decrease in the number of fungi present in the oral cavity in
      patients under antiretroviral treatment as well as higher susceptibility to
      fluconazole.

PMID- 12815801
TI  - [Influence of treating atopic dermatitis with oral antihistamine and topical
      steroids on selected parameters of cell and humoral immunity].
AB  - Pathogenesis of atopic dermatitis (AD) is multifactorial, therefore despite many
      different treatment protocols none of the available methods is effective enough.
      In the present study we analysed the effects of oral antihistamines and topical
      steroids on selected parameters of humoral (immunoglobulin levels) and cellular
      (lymphocyte proliferation index, granulocyte oxidative burst, lymphocyte
      phenotype CD4:CD8) immunity. These parameters were analysed in 34 AD subjects
      during the exacerbation of the disease and after 4 and 12 weeks of the treatment.
      RESULTS: Along with the clinical status improvement (change form 3.17 +/- 0.1 to
      1.3 +/- 0.2; 0-4 scale; p < 0.001), total serum IgE levels decreased
      significantly from 1563 +/- 459 to 1266 +/- +/- 364 IU/ml (p < 0.05). Other
      immunoglobulin levels did not change. Total blood chemiluminescence in response
      to latex stimulation was relatively higher during exacerbation than during
      remission, but this difference was not significant (p = 0.1). Mean spontaneous or
      PMA stimulated chemiluminescence did not differ either. CD4:CD8 index decreased
      significantly during the treatment (from 2.7 +/- 0.3 to 1.8 +/- 0.2; p = 0.03).
      Lymphocyte proliferation in response to PHA was significantly lower during
      exacerbation than during remission (10.4 +/- 2.8 vs. 27.1 +/- +/- 5.2; p < 0.03)
      and the improvement was observed after first 4 weeks of the treatment reaching
      the levels found in healthy controls. Proliferation index in response to anti-CD3
      mAb (OKT-3) was in turn significantly higher during exacerbation (19.1 +/- 3.4
      vs. 11.2 +/- 2.0; p = 0.04). CONCLUSIONS: Oral antihistamine in combination with
      topical steroids leads to several significant changes in the immune parameters
      (IgE levels, CD4:CD8 and proliferation indexes) which may explain its high
      effectiveness in majority of patients with AD.

PMID- 12815802
TI  - [Myoelectric function, metabolism, intestinal circulation and vagal activity
      after chemical sympathectomy].
AB  - Adrenergic innervation plays an important role in the control of electric
      activity and circulatory parameters of the gut. Importance of adrenergic system
      as a modulator of motor, neural and metabolic activity of the intestine is
      studied extensively but still not well understood. We use 6-OHDA a neurotoxin and
      a blocking agent of adrenergic fibers, to evaluate their exact role in the
      control of vital parameters of the intestine and vagal nerves. 50 Wistar rats
      were used. Animals were fasted 24 h prior to experiment with free access to water
      allowed. Acute experiments were performed on 30 rats, divided in the three
      groups. Four experimental groups were established. I--sham operated. II and III-
      pretreated with 6-ODHA (25 mg//kg/24 h s.c.) 3 days before experiment. IV group
      were used for chronic procedure. Thiopental anesthesia (Vetbutal Biovet) was
      applied. Animals were artificially ventilated with positive pressure rodent
      ventilator (Ugo Basile), and heated with continuous temperature control by rectal
      thermistor (FST). Left carotid artery was cannulated and connected with electro
      manometer--arterial pressure (AP) was expressed in mm Hg. Right jugular vein was
      cannulated for continuous saline administration 0.2 ml/h. Mesenteric blood flow
      (MBF) was recorded with use of ultrasonic probe (Transonic systems T206).
      Microcirculatory blood Flow (LDBF) was estimated by laser Doppler flowmetry
      (Periflux 2001 Master). Arterio-venous difference (AVO2) was estimated from whole
      blood (AVOXimeter 1000 E). Oxygen uptake was calculated from MBF and AVO2 and
      expressed in ml/min/100 g tissue. Chronic experiments were performed on conscious
      animals with electrodes implanted to the serosal surface of the intestinal wall.
      Measurements of intestinal myoelectric parameters were performed one, two and
      three weeks after 6-OHDA administration. Vagal activity was recorded in left
      vagus nerve in the neck with suction electrodes (one month after 6-OHDA). 6-OHDA
      pretreatment evoked increase of dominant slow wave frequency by 0.1 Hz from 0.62
      +/- 0.10 to 0.74 (+/- 0.03) Hz in the first week after treatment (p < 0.05). Slow
      wave frequency was no markedly influenced in acute experiments. In the chronic
      experiments after initial increase gradual decrease of slow wave frequency was
      observed reaching control values of 0.62 +/- 0.17 Hz after 28 days. After 6-OHDA
      administration in chronic experiments no substantial changes in slow waves
      amplitude was observed. Frequency and amplitude of spikes activity in vagus nerve
      after sympatectomy increased from 7.96 +/- 1.3 to 10.3 +/- 2/min and 0.18 +/-
      0.09 to 1.13 +/- 0.8/mV. Chemical denervation evoked increase of MBF and LDBF by
      18 +/- 3.6% and 22 +/- 6.4% respectively. Intestinal oxygen uptake (VO2) was
      increased by 10.2 +/- 1.2% in comparison to control. Heart rate and arterial
      pressure was decreased by 18 +/- 4% and 12 +/- 2.4% respectively in comparison to
      control. Adrenergic system plays profound role in the modulation of both
      myoelectric and motor activity of the intestine in the rat. Continuous activity
      of adrenergic neurons affects vascular conductance, capillary density and oxygen
      diffusion parameters.

PMID- 12815803
TI  - [Bone metabolism in men].
AB  - The aim of this paper is to review the main physiologic features of bone
      metabolism in male. A brief description of bony cells and function is given.
      Hormonal influences on bone biology are described. Although androgens have been
      considered as essential in the regulation of bone metabolism in men, recent data
      have emphasised the fact that estrogens could play a dominant role.

PMID- 12815805
TI  - [The role of bisphosphonates in the treatment of bone metastases from urogenital
      cancer ].

PMID- 12815804
TI  - [Pathophysiology of bone metastases].
AB  - The aim of this review is to detail the pathophysiologic mechanisms occurring
      during bone metastases. osteolytic and osteosclerotic metastases are observed
      after migration of malignant cells coming from a primitive tumour which can
      localize and grow inside the hematopoietic bone marrow. Bone lesions observed
      during hematologic malignancies (lymphomas and myeloma) are not detailed here.
      The various cytokine networks that are occurring in bone metastases are detailed:
      in both cases there is a "vicious circle" between the the tumoral cells and bone
      cells responsible for the physiological remodeling of bone. The knowledge of
      these interferences permits to understand the use of anti-osteoclastic treatments
      (bisphosphonates) in osteolytic as well as osteosclerotic metastases.

PMID- 12815806
TI  - [Osteoporosis due to androgen suppression therapy in men with prostate cancer].

PMID- 12815807
TI  - [Bisphosphonates and bone metastases of solid tumors: therapeutic interest
      despite its anti-resorptive properties].

PMID- 12815808
TI  - [Treatment of bone metastases: therapeutic strategies in 2003].

PMID- 12815809
TI  - [Results of a karyological study of blood-sucking flies (Diptera: Simuliidae) of
      Armenia].
AB  - Karyotypes of 31 species of black flies belonging to 11 genera have been
      examined. The morphology of polytene chromosomes from salivary glands of larvae
      and mitotic chromosomes of gonads and ganglia have been studied. It was found
      that most species have 2n = 6, except the Eusimulium species, which have 2n = 4.
      Each species is characterised by a specific pattern of polytene chromosomes. It
      was found that widely spread species are polymorphic in heterozygous inversions
      and additional B-chromosomes. The use of karyological studies in taxonomic
      diagnostics of black flies, especially in the cases when species are similar
      morphologically, was shown to be expedient.

PMID- 12815810
TI  - [Ectoparasites of the zokor Myospalax myospalax (Rodentia) in northern Altai].
AB  - Following ectoparasites have been recorded on the zokor in the Northern Altay:
      specific fleas--Ctenophthalmus dilatatus, Rhadinopsylla ioffi, Brachyctenonotus
      myospalacis; a flea distributed on various rodents; ixodid ticks--Ixodes
      crenulatus, I. persulcatus; gamasid mites--Hirstionyssus myosplalacis. The C.
      dilatatus carried hypopi of acaroid mites.

PMID- 12815811
TI  - [A new mite species Radfordia sigmomys sp. n. (Acari: Myobiidae) parasitizing
      Sigmodon alstoni (Rodentia: Sigmodontidae) from Central America].
AB  - A new myobiid species Radfordia (Hesperomyobia) sigmomys sp. n. (Acari:
      Myobiidae) ex Sigmodon alstoni (Rodentia: Sigmodontidae) from Central America is
      described. This description is based from the females, proto-, dueto- and
      tritonymphs. Female (4 spec.). Body 500-510 (in micrometers) long and 295-320
      wide. Length of setae: ve 90-95--widely lanceolate, 10-15; vi 23-25, sci 95-105,
      sce 90-100, d1 80-85, d2 70-90, d3 20-25, d4 23-27, l1 75-90, l2 80-85, l3 25-27-
      all narrowly lanceolate; d5 10-15, l4 10-15, ic1 25-30, ic2 80-90, ic3 85-90, ic4
      15-18, pg1 10-15, pg2 30-40, pg3 8-10--all hair-like. Protonymph (2 spec.).
      Idiosoma with 14 pairs of dorsal setae, including el and 2 pairs of very short
      anal setae, and 4 pairs of ventral setae, including l5. Length of setae: vi 25,
      ve 23-25, sci 50-52, sce 125-130, d1 18, d2 16, d3 10-12, l1 10-15, l2 12-16, l3
      10-13--all lanceolate; d4 6, ic1 l1, ic2 25-27, ic3 15--all hair-like. Leg
      chaetotaxy II-III: II coxa 0--trochanter 0--genu + femur 2 (1 solenidion)--tibia
      4--tarsus 7 (1 solenidion), III 0-0-0-3-6. Deutonymph (2 spec.). Setae 14 added.
      Length of setae: vi 25-27, ve 30-35, sci 65-70, sce 120-155, d1 20, d2 16-18, d3
      11-13, d4 10-13, l1 20-27, l2 10-15, l3 l1--all lanceolate; l4 6, ic1 13-15, ic2
      35-40, ic3 25--all hair-like. Leg chaetotaxy II-III: II 0-0-3(1)-4-7(1), III 0-0
      1-3-6. Tritonymph (2 spec.). Setae d5 and ic4 added. Length of setae: vi 34(35),
      ve 45(40), sci 80(75), sce 140(150), d1 23(25), d2 25(25), d3 13(10), d4 13(10),
      l1 100(90), l2 22(25), l3 25(27)--all lanceolate; l4 6(5), d5 4(5), ic1 12(15),
      ic2 45(50), ic3 35(40)--all hair-like; setae 14 microchaetae. Leg chaetotaxy II
      IV: II 1-1-3(1)-4-7(1), III 0-1-1-3-6, IV 0-0-1-3-4. This new species is closely
      related to R. (H). sigmodontis Radford, 1951 ex Sigmodon hispidus from USA. The
      females of these two species are not distinguishable from each other. While the
      tritonymphs differ by the following characters. In R. (H.) sigmomys sp. n., the
      length of setae ic2 and ic3 are 40-50, sci--75-80, l1 90-100. In R. (H.)
      sigmodontis, the setae ic2 and ic3 are microchaetae, the setae sci and l1 are 30
      40 and 10-15 in length respectively.

PMID- 12815812
TI  - [Addition to the fauna of mosquitoes of the family Culicidae (Diptera) of the
      Novgorod region].
AB  - Mosquitoes of 26 species of the family Culicidae were found in the Novgorod
      Province. During the researches in 1996-2001, five new species for the region
      were found: Aedes annulipes, Ae. impiger, Ae. riparius riparius, Ae. rossicus and
      Culex torrentium.

PMID- 12815813
TI  - [Features of pathogenesis of Diplostomum infection in riverine Abbottina
      rivularis (Cypriniformes: Cyprinidae) from Primor'e].
AB  - Autopsies of Abbottina rivularis from southern Primorye (drainage-basin of
      Artyomovka River, Razdolnaya River and Khanka Lake) and southern Sakhalin Island
      (Maloye Chibisanskoye Lake) revealed high indices of diplostomum-infected lenses
      of these fishes. The metacercariae have been identified as Diplostomum
      parviventosum Dubois, 1932, D. huromense (La Rue, 1927), D. helveticum (Dubois,
      1929), D. mergi Dubois, 1932, Diplostomum sp. The most lenses of parasitized eyes
      possessed dorsally situated sperical protrusions of the lens capsule ("cyst").
      Earlier, this phenomenon was found by Larson (1965) in naturally infected
      bullheads (Ictalurus). The metacercarial infection level and its dynamics, age
      composition of metacercariae in both lenses and "cysts", and "cysts" production
      are discussed.

PMID- 12815814
TI  - [Distribution of the cestode Caryophyllaeides fennica (Cestoda: Lytocestidae) in
      the population of cyprinid fish in the Rybinsk water reservoir].
AB  - The distribution of the cestode Caryophyllaeides fennica in populations of the
      ide, roach, white bream and bream from the Rybinsk reservoir has been analyzed in
      regard to fish age. The relative abundance of C. fennica in populations of each
      host species was calculated as product of the helminthes abundance by the fish
      number in age groups. The highest prevalence and abundance of cestodes was found
      in the ide. All age classes of this species were infected, with the maximum in
      fishes of the age 3+ ... 5+. The roach is infected with C. fennica till only 10
      year age; brean is infected till the age 4+. In the white bream C. fennica is an
      occasional parasite. The cestode number among hosts was as follows: bream--68%;
      roach--26%, ide--5%, white bream--1%. Different approaches to the estimation of
      the parasite abundance distribution among several host species (in terms of mean
      prevalence and intensity of the relative abundance of parasites) are discussed.

PMID- 12815815
TI  - [Polypodium hydriforme in the eggs of the sterlet from the northern Dvina river].
AB  - The paper provides data on the invasion of Acipenser ruthenus (sterlet) in the
      North Dvina River by Polypodium hydriforme (Cnidaria). Prevalence and intensity
      of invasion proved to be similar for two fishing sites. Prevalence of invasion
      exceeded 88%, thus being exceptionally high for P. hydriforme. Intensity of
      invasion was from 1 to 436 eggs per female. A verage percentage of infected eggs
      was about 1%.

PMID- 12815816
TI  - [Formation of parasite fauna in the bullhead (Cottus gobio L.) (Pisces:
      Cottidae)].
AB  - The formation of parasite fauna in the bullhead Cottus gobio L. in different
      water bodies was examined. The largest number of parasite species including
      specific parasites was observed in the Onega and Ladoga lakes. It is suggested
      that the host and their parasites migrated namely from these water bodies to
      other part of the range of the bullhead.

PMID- 12815818
TI  - [The trematode Lecthodolfusia anatina (Pleurogenidae) and its life cycle in
      Primor'e].
AB  - The trematiode Lecthodolfusia anatina Kchotenovsky, 1967 is redescribed.
      Experimental study has shown, that in the Primorye land, the first intermedial
      host of this trematode is a mollusk Boreoelona contortrix ussuriensis, and the
      second ones are larvae of the may fly Ecdyonurus aurarius and caddis flies
      Semblis phaenoides and Groerodes sp. Adult worm were reared in chickens.

PMID- 12815817
TI  - [Crepidula beklemishevi gen. et sp. n. and Dimeiospora palustris gen. et sp. n.
      (Microspora: Amblyosporidae)--new microsporidian genera and species from blood
      sucking mosquitoes (Diptera: Culicidae) from the south of the western Siberia].
AB  - Microsporidia parasitizing the adipose body of mosquito larvae of Anopheles
      beklemishevi and Aedes punctor has been studied. Two new genera of microsporidia
      are described based on lightmicroscopic and ultrastructural characteristics of
      spores and sporogony stages. The spore wall of Crepidula beklemishevi gen. n. et
      sp. n. is formed by two-membrane exospore, thick exospore, bilayer endospore and
      thin plasmolemma. Spores with single nucleus, polar filament anisofilar, with 6-7
      coils (2+ 4-5), polaroplast consisting of three parts: macrochelicoidal,
      microhelicoidal and lamellar. Fixed spores 4.2 +/- 0.22 x 2 +/- 0.01 microns. The
      sporogony of Dimeiospora palustris gen. et. n. results in spore formation of two
      different types. Spores of the first type are oviform, with thick wall, single
      nuclear, 6.1 x 4.9 microns. Spore wall with three layers, about 370 nm. Exospore
      electron-dense, subexospore moderately electrondense. Exospore and subexospore
      irregularly pleated on the almost spore surface and slightly thinner on anterior
      end only. Endospore electron-translucent. Polar filament anisofilar, with 9 coils
      (3 + 6). Polaroplas consists of three parts: lamellar, fine bubbled, and coarse
      bubbled. Spores of the second type broad-ovate, with apical pole narrower, distal
      pole concave, 4.6 x 3.7 microns. Spore wall with three layer, 355 nm. Exospore on
      the apical end irregularly pleated, consists of thin electrondense exospore,
      subexospore of variable electron density, endospore electron-translucent. Polar
      filament anisofilar, with 13 coils (3 + 10). Polaroplast has two parts: lamellar
      and vesicular.

PMID- 12815819
TI  - [New species of myxosporidia (Myxozoa: Myxosporea) of fish from the northwestern
      Sea of Japan].
AB  - Three new species of mixosporidia of the genera, Myxidium and Myxoproteus, from
      the gall bladder and urinary bladder of fishes from Japan Sea: Myxidium licodae
      sp. n., M. rarum sp. n., and Myxoproteus ovale sp. n.

PMID- 12815820
TI  - [New species of coccidia Eimeria stizostedioni sp. n. (Sporozoa: Coccidea) from
      the pike perch Stizostedion lucioperca (Perciformes)].
AB  - A new coccidia species Eimeria stizostedioni from the pikeperch Stizostedion
      lucioperca (Perciformes) is described. Localities: Neva river. Prevalence: 20%
      (1/5). Intensity of infection weak. Oocysts 7.5-8.0 x 10.0-12.5 microns. The form
      varies from oval up to ovoid; a wall is sleek, colourless, single-layer two
      planimetric, micropyle, the polar granules and residual body are absent.
      Sporocysts 3.5 x 6.5 microns, with Stieda body and residual body represented by
      few small granules. Sporogony is endogenous.

PMID- 12815821
TI  - The return of the smallpox vaccination. Nurses report on plans, concerns.

PMID- 12815822
TI  - Recalling 1947 smallpox outbreak. Nurse helped vaccinate New Yorkers in massive
      effort.

PMID- 12815823
TI  - Injecting non-nurses into the equation.

PMID- 12815824
TI  - [Analysis of activities carried out by nurses at health facilities in Milan.
      Results of a study].

PMID- 12815825
TI  - [Objects of study, material and formal, in nursing science].
AB  - The use of expression "nursing science" in nursing literature is widespread. The
      word "science" derives from Latin scientia, that is knowledge. "Knowledge" means
      to posses a series of learning and cognition learned by the study, the experience
      or the observation. Every specific area of the knowledge take the name of
      science. But in what area of the general learn is nursing knowledge interested
      in? We try to give an answer with this article. We try an epistemological
      analysis of the interest nursing material object (manperson) and of the formal
      object: it's still lack a scientific community's agreement on this last. In the
      end, in last analysis, we try to suppose the epistemological's aim of nursing
      knowledge as regards to the formal object identified.

PMID- 12815826
TI  - [Health support staff: resources or links for nurses?].
AB  - How to open the doors to the new support personnel (OSS)? An enquiry has been
      elaborate to understand if the nurse were ready to welcome this figure in order
      to explore the competences and the responsibilities that the nurses attribute to
      the OSS The limited organizational rationality of the assistance, especially in
      the public, determines waste of resources and low general effectiveness. In this
      scenery the challenge for the profession consists of guaranteeing suitable relief
      levels, despite the serious lack of resources. The nursing profession n, to
      welcome the OSS needs to analyse and clarify its operatives and the models of
      collaboration with the other health care professionals.

PMID- 12815827
TI  - [The integration process between nurses and support figures. Experience at the
      AULSS 16 in Padua].
AB  - In the last decade, Italian Nursing history had an important normative
      development that completely redesigned profile, responsibility, autonomy and
      education, giving a push to the professionalism process. The article discuss how
      introduce new support figures, what tasks to delegate and what procedure are
      necessary to better care.

PMID- 12815828
TI  - [Documentation of the care process for prevention and treatment of decubitus
      lesions: the audit method].
AB  - The article describes an experience of evaluation of the quality of nursing care
      applied to the documentation of prevention and treatment of the Pressure Lesions
      (LDD). Overseeing specific programme has been implemented, with the purpose to
      appraise the completeness of the documentation used for recording data and the
      conformity of the relief interventions in comparison with those of the protocol.
      The quality of the documentation is fundamental to the evaluation of the program.

PMID- 12815829
TI  - [Milestones in the history of intestinal anastomosis].
AB  - Description of the most important steps in the evolution of intestinal suture
      technique: The simple Lembert suture and its precursors, the two-layer suture,
      and the adapting one-layer suture. The contributions of Ph. F. Ramdohr.
      Wolfenbuttel, 1727, A. Lembert, Paris, 1826, F. Wydler, Aarau, 1865, and Th.
      Kocher, Bern, 1878-1907, are presented in more details.

PMID- 12815830
TI  - [Influential factors in anastomosis healing].
AB  - Anastomotic leakage after visceral surgery is one of the most important and
      feared complication. According to the literature the rate of clinically apparent
      anastomotic leakage ranges from 3.4% to as high as 12% and at least one third of
      the mortality after colorectal surgery is attributed to leaks at the anastomotic
      site. Within this context, knowledge of factors influencing anastomotic healing
      appears even more important. Beside surgical-technical (suture technique, suture
      material) and surgical-tactical factors (primary anastomosis vs. discontinuity
      resection or formation of protective diverting stomas) knowledge of the various
      endogenous (diabetes, sepsis, infection, malnutrition) and exogenous factors
      (steroids, radiation, preoperative bowel preparation) influencing anastomotic
      healing is essential. Recently, it has been demonstrated that Mycophenolate
      mofetil, an immunosuppressive drug that is currently used in transplantation and
      in chronic inflammatory diseases significantly impairs mechanical stability of
      the healing anastomosis. In contrary, local application of keratinocyte growth
      factor (KGF) as well as insulin-like growth factor-I (IGF-I) have been shown to
      accelerate and improve anastomotic healing and mechanical stability in an animal
      model. Studies that will identify further factors and drugs influencing
      anastomotic healing are of great importance since the use of such drugs could
      have enormous clinical implications. The traditional use of temporary diverting
      stomas following operations such as coloanal anastomosis or ileopouch anastomosis
      as well as Hartmann's discontinuity resection could be eliminated even in
      immunocompromised or other high risk patients.

PMID- 12815831
TI  - [Gastrointestinal extramucous running suture anastomosis].
AB  - There is an ongoing discussion in surgery about what is the best or "correct"
      technique for gastrointestinal anastomosis. An ideal anastomosis should fulfill
      the following criteria: it must be well vascularised, safe ("waterproof"), easily
      feasible, tension-free, spillage should be avoided and it should be inexpensive.
      We give an illustrated report of the surgical technique of the continuous single
      layer anastomosis in the gastrointestinal tract. On the basis of a pilot study, a
      randomised comparative study, a Swiss multicenter trial and, finally, a
      prospective 5-year-follow-up quality control study we demonstrate that this
      "Schweizer (Swiss)"-technique fulfills the criteria of an "ideal" anastomosis and
      can be used in almost all intestinal localisations.

PMID- 12815833
TI  - [Does conservative therapy of chronic inflammatory bowel diseases still play a
      role?].
AB  - The first-line therapy for inflammatory bowel disease flares is typically medical
      in nature. Glucocorticoids are a mainstay for the treatment of severe
      inflammatory bowel disease. Aminosalicylates are efficacious in the treatment of
      active mild- to- moderate disease. Infliximab, a chimeric monoclonal anti-TNF
      alpha antibody can be used in refractory Crohn's disease. The recurrence rate
      after surgery or medical therapy is high. Therefore the introduction of a
      maintenance therapy is important in patients with repetitive flares. In patients
      with ulcerative colitis aminosalicylates are useful as maintenance therapy. In
      severe ulcerative colitis or in Crohn's disease immune suppressive strategies
      such as a therapy with azathioprine, 6-mercaptopurine or methotrexate should be
      considered. In Crohn's patients with fistula surgical treatment or a therapy with
      antibiotics, immunosuppressants or infliximab is recommended.

PMID- 12815832
TI  - [Carcinomas of the esophago-gastric junction: surgical strategies].
AB  - There is increasing incidence of adenocarcinoma of the esophagastric junction
      (EGJ) especially in young white men (+35% in 30 years). The reasons for this are
      not yet well known, however one of the main causes is gastro-esophageal-reflux
      disease (GERD). The differentiation of a EGT carcinoma in three subtypes is
      important for therapy: adenocarcinoma of the distal esophagus (type I), cardia
      carcinoma (type II) and subcardial gastric carcinoma (type III). The most
      important risk-factor for type I-cancers is "barrett's metaplasia" resulting from
      GERD over years. The risks for the type II- and type III-carcinomas may be
      obesity and high caloric and fat intake. The role of Helicobacter pylori
      infection and adenocarcinoma of the subcardia is unproven. Preoperative tumor
      staging is difficult and tumor-stage is most often underestimated (esp. in the
      case of a high-grade dysplasia where in 43% carcinomas one already established).
      Therapy for all three types of EGJ tumors is surgical. Transhiatal (rarely
      transthoracic) esophagectomy with lymphadenectomy and proximal gastrectomy is
      performed for type-I-tumors, type-II and III-tumors are treated like a gastric
      cancer with total gastrectomy, lymphadenectomy and distal esophagectomy. Lymph
      node metastases and advanced tumor-stage are bad prognostic factors, complete
      tumor resection (R0 resection) with extended lymphadenectomy will improve
      prognosis. The results of a preoperative combined-modality therapy are
      encouraging, but have not yet shown a definitive benefit. In case of distant
      metastases, radio-chemotherapy combined with gastroenterologic treatments (e.g.
      esophageal prostheses, PEG, etc.) will be used as a palliative treatment option.

PMID- 12815834
TI  - [Pancreatic pseudocysts--possibilities in surgical therapy].
AB  - Based on the classification of pseudocysts according to D'Egidio and Schein the
      different surgical techniques for the treatment of pancreatic pseudocysts, i.e.
      drainage procedures and resections are discussed. The role of laparoscopic
      techniques is demonstrated. The "competing" endoscopic and interventional
      techniques are mentioned. The prognosis of the patients after operations for
      pancreatic pseudocysts is to a smaller degree depending on the operating
      technique, but largely on the natural history of the disease and the
      discontinuation or continuation of the underlying pathogen.

PMID- 12815835
TI  - [Technique of pancreatic anastomosis].
AB  - Postoperative morbidity after pancreatic resection is primarily due to leakage of
      the pancreatic anastomosis. The duct-to-mucosa pancreatico-jejunostomy either as
      an end-to-end or end-to-side anastomosis is the preferred technique in our hands.
      The use of a temporarily catheter to drain the main pancreatic duct is optimal.
      The pancreatic leakage rate depends in many series on the consistence of the
      pancreatic parenchyma, the diameter of the major pancreatic duct and the local
      perfusion. A meticulous, standardized technique, the possibility to adapt the
      technique in case of unexpected findings and the operative routine of the surgeon
      are of paramount importance for achieving a low leakage rate. In so called "high
      volume" centers the pancreatic fistula rate today is in the range of 3 to 13% and
      the mortality of pancreatic head resection varies between 0.5 and 3%.

PMID- 12815836
TI  - [Standard technique of oncologic colorectal surgery].
AB  - Who ever is writing about standards should put himself the question: What is a
      standard? How is it produced? Who is defining it? How compulsory is it? A
      standard should only be understood as guiding principles or as following
      guidelines and never as a dogma, while otherwise every operative technical or
      therapeutical progress is prohibited. On the basis of the onco-surgical
      guidelines for the colo-rectal carcinoma is shown how standards can begin to
      sway. The Turnbull "no-touch isolation technique" does not stand up to the
      criteria of the evidence based medicine. The usefulness of the high ligation of
      the veins and the intestinal occlusion has not been proven by any studies. The
      central ligature of the Arteria mesenterica inferior in left resection is wrong
      according more recent anatomical knowledge. Ligation near to the aorta leads
      obligatory to lesions of the plexus hypogastricus. Animal experiments are
      controversial concerning the dissemination of tumour cells during crushing of the
      cancer. And a prospective controlled study does not show any advantage of
      respecting the Turnbull criteria. Independent prognostic factors are the surgeon,
      the frequency of performing the procedure in the hospital concerned, the pT and N
      stage, the R-0 resection and according to American pathologists the pre-operative
      CEA titre. Also are mentioned the infiltration of veins and lymph vessels, micro
      metastases in lymph nodes and the grading. The resection should if possible be
      performed in anatomical layers, specially considering the meso-rectum. What
      should be done in the distal 8 cm till the pelvic floor has not yet been
      clarified. On the contrary, the laparoscopic surgery has definitively also found
      its acceptance in oncological surgery. The discussions about port-metastases and
      tumour-cell-dissemination by the pneumoperitoneum-gas have silenced. Already,
      partially better long-term results are mentioned. In the beginning of 2003, the
      pillars of the standard technique of oncological colo-rectal surgery are besides
      the orthograde intestinal flushing, the pre-operative low molecular Heparin and
      the antibiotic prophylaxis, the open or laparoscopic R-0 en bloc resection, the
      minimal safety distance in the low rectum of 1 cm, the ligature of the Arteria
      mesenterica inferior 2-3 cm distally to its origin from the aorta in case of left
      resection, respectively the Arteria ilio-colica at its origin from the Arteria
      mesenterica superior in case of right resection, the cytotoxic intestinal
      flushing in case of left resection and the flushing of the abdominal cavity as
      well as the port-site with Taurolin 0.5%. In case of rectum-carcinoma uT3 or uN+,
      a neo-adjuvant radio-chemotherapy is administered and adjuvant chemotherapy is
      given by positive nodal colon-carcinoma.

PMID- 12815837
TI  - [Surgical therapy of acute diverticulitis].
AB  - Following conservative treatment of acute colonic diverticulitis at least one
      fourth of the patients experiences a further attack. The complication rate rises
      up to 60% at the recurrence. Therefore, colon resection is indicated at/following
      the second attack. For male patients below 50 years of age and with severe first
      attack, surgery is recommended already at/following the first attack. In the
      absence of diffuse fecal peritonitis, the one-stage colon resection with primary
      anastomosis is widely accepted, now. Percutaneous drainage of a peridiverticular
      or paracolic abscess is hazardous (success rate 70%), dangerous (consecutively
      delayed elimination of septic focus, 5% complication rate of drainage itself) and
      not necessary or helpful. Recurrent diverticulitis following sigmoid resection
      rarely occurs (1-11%) and is avoidable by removal of at least 20 cm colon
      including the rectosigmoid junction and anastomosis to the rectum. An extension
      of the resection towards cephalad direction to remove as much diverticula as
      possible seems not to decrease the risk of recurrent disease and is therefore not
      worthwhile.

PMID- 12815838
TI  - [Stomata--surgical standards].
AB  - The placement of an intestinal stoma is still a common procedure despite the
      recent advantages in intestinal surgery. It is mandatory to apply meticulously
      sound surgical principles in order to achieve good results. Nevertheless,
      intestinal stomas are envisioned with a high perioperative morbidity which is
      mostly caused by surgical inadequacy. This can lead to considerable problems in
      management of the stoma in the long term and ultimately will affect quality of
      life of the patient. The cumulative morbidity can be given by 50% with prolaps,
      hernia, stenosis and necrosis as well as stoma retraction being the most
      relevant. In contrast, an adequate intestinal stoma will positively affect the
      quality of life of the patient. The availability of devices developed by the
      industry and the inauguration of a professional service in certain hospitals
      simplified the management of patients with a stoma. This significantly improved
      the standards of care especially regarding preoperative preparation and
      postoperative management. Thus, most patients are able to maintain an active and
      socially integrated life with minimal physical and psychical limitations.

PMID- 12815839
TI  - [Crohn disease--surgical standards].
AB  - Surgery for Crohn's disease is restricted to the treatment of complications. Even
      then, nearly all patients with Crohn's disease must be operated on at least once
      in lifetime. Surgical concepts base on the right timing for the operation,
      interventional drainage of abscesses, accurate pre-operative work-up to determine
      the extent of inflammation, and bowel conserving operation techniques. Respecting
      these principles, surgery for Crohn's disease can be performed with low
      complication rates restoring in most cases patients' quality of life.

PMID- 12815840
TI  - [Serologic diagnostic of Toxoplasma gondii infections].
AB  - The diagnostic of T. gondii infection is one of the most interesting features of
      the disease for investigators, since parasitological diagnostic is difficult to
      reach in the early period of the infection. The diagnostic is exclusively based
      in the detection of serum specific antibodies (IgG, IgM, IgA, IgE) and more
      recently, in the avidity of serum IgG. No matter the high specificity and
      sensitivity of the test used for diagnostic, one test sample is not enough to
      inform us about the antibody type as a parameter for early or late period of
      infection.

PMID- 12815841
TI  - [Seminal profile in workers exposed to cholinesterase inhibitor insecticides].
AB  - The objective of this study was to determine the physical, chemical and
      cytomorphologic characteristics of semen obtained from workers exposed to
      cholinesterase inhibitor insecticides and compare them with samples of the same
      nature obtained from unexposed subjects, and in addition, to correlate those
      findings with blood levels of cholinesterase. The study group consisted of 29
      adult males, age range 20-54, that were exposed to cholinesterase inhibitor
      insecticides during 4 hours per day for a variable lapse (one year minimum),
      whereas the control group consisted of 30 unexposed individuals of the same
      gender, and similar age range. A thorough medical examination was performed in
      every individual. It consisted of an occupational medical history and complete
      physical exam. A blood sample was obtained in all the subjects in order to
      determine total cholinesterase levels by the modified S. Hestrin Hydroxamate
      method. Semen analysis was done in specimens collected after recent masturbation
      following a 3-day abstinence period. The data was processed and analyzed by the
      SAS computerized statistics program. The results revealed significant differences
      between both groups (p < 0.05) for the following variables: sperm count per mL.,
      percentage of fast, mobile and immobile, live and dead spermatozoids. Spermatozoa
      morphology was found to be within normal limits as established by the WHO.
      Nevertheless, the differences related to the percentage of big head and amorphous
      spermatozoids was significant (p < 0.05). The results indicate that
      cholinesterase inhibitor insecticides affect certain variables of the semen
      analysis and hence the quality of the semen.

PMID- 12815842
TI  - A study about the effect of vitamin E on hyperlipidemia and atherosclerotic
      lesions in New Zealand white rabbits fed with a 1% cholesterol rich diet.
AB  - The purpose of this study was to determine whether the administration of Vitamin
      E (200 mg/day) for 4 weeks could decrease hypercholesterolemia and inhibit
      atherosclerosis in male hypercholesterolemic New Zealand White rabbits. Plasmatic
      Total Cholesterol (TC) and LDL-Cholesterol (LDLc) were determined by enzymatic
      methods and Vitamin E was determined in plasma by HPLC at weeks 0, 4 and 8. A
      histopathological study was carried out at week 8 (w 8), using a hematoxylin
      eosin method. Forty rabbits were divided randomly into 5 groups and fed different
      diets. These diets included a Normal diet, a 1% Cholesterol rich diet, a Normal
      diet + Vitamin E and 1% Cholesterol rich diet + Vitamin E. The findings did not
      show a reduction of Total Cholesterol and LDLc in the groups of rabbits that
      received Vitamin E (III and IV) at weeks 4 and 8. At the end of the experiment,
      all the animals were deeply anesthetized with hydrochloride ketamina (60 mg/kg
      body wt) in order to carry out a histopathological study. Regarding the
      atherosclerotic lesions, Vitamin E did not induce inhibition of the
      atherosclerotic plaque development or any modification in the lesion type induced
      by the hypercholesterolemic diet. In conclusion, the results suggest that
      additional studies need to be carried out with higher doses and/or treatments for
      a longer period in order to clarify in detail whether Vitamin E really has a
      hypocholesterolemic effect and inhibits atherosclerosis.

PMID- 12815843
TI  - [Increase in nitric oxide concentrations in serum and mononuclear cell cultures
      from patients with Type II reaction state of Hansen's disease].
AB  - The word "reaction" is used in leprosy to describe signs and symptoms of acute
      inflammation. Type II reactions, including erythema nodosum leprosum (ENL) occur
      in the multibacillary forms of Hansen's disease. Nitric oxide (NO) could play a
      role in the response of the host, where a high NO production would be involved in
      acute inflammatory processes. In this paper we evaluate NO production in serum
      and in the supernatants of mononuclear cell cultures (MNCC), measured indirectly
      by Griess' method. The results obtained in serum showed that 52% of patients with
      ENL (15/29) had a production over 30 microM, distributed as follows: 8/15 had a
      mean concentration of 36.38 +/- ?5.71 microM; 1/15, 70.5 microM and 6/15 had a
      mean concentration greater than 100 microM (205.97 +/- 5 microM). Forty eight
      percent presented nitrite and nitrate levels lower than 30 microM (18.93 +/-
      6.15). Only supernatants of mononuclear cell cultures from ENL patients collected
      at 120 hours of incubation presented NO production levels higher than 10 microM
      +/- 6.53, as compared with the supernatants from the stable polar forms of the
      disease (lepromatous leprosy and tuberculoid leprosy), where values were 2.52
      microM +/- 1.18 and 2.69 microM +/- 1.07, respectively. These preliminary results
      show a different metabolic activity in the group of patients with Type II
      reaction state (ENL).

PMID- 12815844
TI  - Tortuosity of terminal arterioles in the basal ganglia is increased in status
      lacunaris.
AB  - The goal of this study was to evaluate the participation of small (diameter
      between 26 microns and 90 microns) and terminal (diameter between 10 microns and
      25 microns) arterioles in the status lacunaris of the basal ganglia and to
      classify tortuous vascular profiles based on morphometry. Paraffin sections, 40
      microns thick, of the basal ganglia from autopsied patients over the age of 45,
      were stained with PAS. A three-dimensional microscope, R400 (edge) was used to
      evaluate the structure of the blood vessels. Six patterns of the tortuous
      profiles were identified: simple kink, loop, knot, tangle, coil, and wave, and
      well as their combinations. Tortuous arterioles in the basal ganglia were present
      both in control group and status lacunaris cases. However, statistical Student's
      t-test analysis revealed a significant increment in the number of microfields
      containing tortuous terminal arterioles in the status lacunaris group (mean 7.50
      +/- 4.62) versus the control group (mean 2.92 +/- 1.38) (p = 0.001). A risk for
      status lacunaris was associated with the increased frequency of tortuous terminal
      arterioles (Odd ratio = 1.94, 95%-Confidence Interval = 1.17-3.22) (p = 0.008)
      but not small arterioles (Odd ratio = 1.64, 95%-Confidence Interval = 0.62-4.38)
      (p = 0.39). Our findings suggest than an increased number of tortuous terminal
      arterioles is associated with status lacunaris. Six characteristic patterns of
      the tortuous profiles as well as their combinations were identified.

PMID- 12815845
TI  - [Moebius syndrome due to the use of misoprostol. Case report].
AB  - We report a patient affected with Moebius Syndrome (OMIM 157900) due to the use
      of misoprostol during the first trimester of the pregnancy, when abortion was
      intended twice using this drug, vias vaginal (600 mg) and oral (900 mg), with
      failure to induce abortion on both occasions. Since the use of misoprostol for
      abortion, without any medical indication or supervision, appears to be rather
      frequent in our population and since there are reports of severe malformations in
      children born after failed intents of abortion with this medication, it is
      necessary to alert the medical community and the population in general about the
      teratogenic risks of this drug.

PMID- 12815846
TI  - [Hemorrhagic syndrome induced by caterpillars. Clinical and experimental studies.
      Review].
AB  - Patients affected with the hemorrhagic syndrome caused by contact with
      caterpillars of the Lonomia genus show digestive, pulmonary and intraperitoneal
      bleeding in combination with hematomas and echymosis. Hematuria is also
      frequently seen. Blood coagulation tests show prolongation of PT, aPTT and ThT.
      There is a decrease of Fg, FV, FXIII, Pg and alpha 2AP. Factor VIII and FvW are
      increased while the platelet count is unaffected. FDP's are increased and D
      dimers are present in most cases. Treatment with whole blood or fresh frozen
      plasma worsens the clinical picture causing a severe drop in the platelet count
      often leading to renal failure and death. However, if antifibrinolytics, either
      alone or in combination with cryoprecipitate or purified fibrinogen, are
      administered, no change in the platelet count can be detected and the patients
      recover rapidly. It is concluded that this syndrome is caused by a mild
      disseminated intravascular coagulation (DIC) in combination with a
      hyperfibrinolytic state; the former being partially obscured by the latter, that
      manifests on administration of whole blood or fresh frozen plasma. Activators of
      FII, FV and Pg, and compounds showing FXa, plasmin and kallikrein-like activities
      have been identified in the Lonomia achelous venom. Proteases capable of
      degrading FXIII and extracellular matrix protein and an inhibitor of FV have also
      been isolated from these species. In Lonomia oblique, activators of FII and FX
      and an enzyme with phospholipase-like activity have been identified. In rabbits,
      subcutaneous injection of crude extract and one of the chromatographically
      purified fractions of Lonomia achelous venom causes a decrease of Fg, Pg and
      FXIII. Intravenous administration of the same fraction causes lysis of preformed
      thrombus with decrease of Fg, Pg and FXIII in combination with inhibition of
      thrombus growth. It should be noted that, under the same conditions, injection of
      Lonomia obliqua prothrombin activator causes a DIC.

PMID- 12815847
TI  - [Long-range interactions between macromolecules in ordered media].
AB  - The results of theoretical calculations of interactions between macromolecules
      dissolved in ordered media such as liquid crystals and biological membranes
      (lipid bilayers) are reviewed. Expressions for the potentials of interactions
      between macromolecules of different shape incorporated into nematic liquid
      crystals, thin films, and lipid mono- and bilayers were derived. In addition to
      exact expressions, simple evaluating formulae are given. The two-dimensional
      "gas" of macromolecules swimming on the membrane was considered, and the
      expression of state for this "gas" was derived. It was shown that in the "gas",
      phase transitions accompanied by the formation of two-dimensional clusters may
      occur. The estimates of critical density at which these transitions occur are
      given.

PMID- 12815848
TI  - [Voltamperometric study of adsorbed ferredoxin from Azotobacter vinelandii].
AB  - The influence of various factors on the electron-transfer activity of ferredoxin
      I from Azotobacter vinelandii was studied. The method of cyclic voltammetry was
      used to obtain the data.

PMID- 12815849
TI  - [Method of decomposing spectra using the original spectrum and its derivatives].
AB  - A method for the decomposition of optical spectra into bands was proposed, which
      is based on simultaneous approximation of the initial spectrum and its
      derivatives. The bands of the standard (gaussian) form were used in the
      decomposition procedure. A method for the selection of the optimal smoothing
      filter was described. The efficiency of the proposed method was demonstrated on
      model and experimental absorption spectra. It was shown that this method makes it
      possible to determine the number of bands and its parameters more exactly than
      the standard approach based on the analysis of one derivative of one power.

PMID- 12815850
TI  - [Change in spectral properties of nitrosohemoglobin induced by UV light].
AB  - The effect of UV radiation on the spectral characteristics of human
      nitrosohemoglobin in a wide dose range (151-4530 J/m2) was studied. It was shown
      that the irradiation of hemoprotein solutions with low doses of UV light (151-453
      J/m2) led to local conformational rearrangements of the iron porphyrin moiety of
      the molecule. The apoprotein exhibited a high photostability under the conditions
      of the experiment. High doses of UV radiation (1359-4530 J/m2) induced the
      accumulation of methemoglobin in the protein sample. A scheme of the photoinduced
      formation of methemoglobin was elaborated.

PMID- 12815851
TI  - [Conditions, necessary for realizing the catalytic effect of enzymes: role of the
      environment].
AB  - A hypothesis of enzymic catalysis was put forward according to which the energy
      of the exothermic reaction that takes place in aqueous medium is used for a shift
      of equilibrium in the endothermic reaction, a reaction involving hydrated ions.
      This occurs in accordance with the Le Chatelier's principle, and, as a result of
      water dissociation in a homogeneous medium, a gradient of H+ and OH- ions is
      generated at the water/protein interface. It follows from the hypothesis that the
      chemical conversion of the substrate to the product is preceded by the attack of
      hydrated ions on the protein and their association on the protein (attack of the
      nucleophilic agent followed by the acception of the proton). This results in the
      formation of a cyclic peroxide in the amino acid residue and a C=O-->[C=O]*
      transition. The return of the carbonyl to the ground state makes it possible to
      store a part of free energy and use it for converting the enzyme to a state with
      a higher conformational energy. Thus, we consider the electron excited state in
      the protein as a state necessary for dark reactions. This implies that, in
      addition to the effect of sorption of substrate on protein, another aspect of
      behavior of the dynamic system should be taken into account. All factors
      producing a real effect on the internal protein dynamics are important for the
      conformational transition and enzymic reaction as a whole, and the rate constant
      should be determined with allowance for these factors.

PMID- 12815852
TI  - [Photoinduced enzymatic epimerization of glucose].
AB  - The possibility was examined whether weak external electromagnetic radiation can
      affect the parameters of enzymic reactions. It was found that, in a system
      involving an aqueous solution of concanavalin A, glucose, and erbium salt exposed
      to helium-neon laser light of a wavelength of 633 nm, epimers of glucose: allosa,
      mannose, and galactose are formed. The effect observed was found to represent a
      photoinduced enzymic reaction in which the protein dissolved in water converts
      the glucose associated with it into epimers by the action of electromagnetic
      radiation. The photoepimerase activity of concanavalin A was established for the
      first time.

PMID- 12815853
TI  - [Self-diffusion of water into silk fibers from magnetic field pulse gradient
      data].
AB  - Self-diffusion of water was studied in fibers of natural silk (Bombyx mori) with
      a water content of 0.18 g H2O/g dried material. Self-diffusion measurements were
      conducted by pulsed gradient of magnetic field (stimulated echo) at diffusion
      times from 10 to 200 mc. The dependence of experimental diffusion coefficients
      Dexp = f(delta) (observed decrease when delta increased) was determined to be
      responsible for the restricted diffusion. A model of planar and regularly spaced
      permeable barriers to diffusion of water molecules was applied to estimate the
      barrier spacing a and the permeability constant p. The maximal value of Dexp (at
      short diffusion time) in B. mori silk fibres was about 0.06 of the value of Dexp
      in bulk free water. The results obtained are compared to literature data on self
      diffusion of water in hydrated biopolymer fibers and are discussed in connection
      with molecular mobility in natural macromolecular systems with low water content.

PMID- 12815854
TI  - [Kinetics of the lactone-carboxylate transition of hybrid camptothecin-netropsin
      molecules].
AB  - The kinetics of the hydrolysis of the lactone ring of a hybrid molecule
      containing the molecules of the antitumor drug camptothecin and a derivative of
      the antibiotic netropsines, which is highly affine and specific to the DNA A-T
      sequences was investigated. It was shown that intramolecular interaction
      significantly slows down the rate of hydrolysis but does not change the
      equilibrium ratio of concentrations of the lactone and carboxylate forms of the
      camptothecin fragment of the hybrid molecule, which corresponds to the pH value.
      The use of intramolecular interaction for controlling the kinetics of the
      lactone/carboxylate transition makes it possible to create the drugs of the
      camptothecin family, which preserve the biologically active lactone form under
      the physiological conditions for a longer time and, therefore, are more effective
      as anticancer agents.

PMID- 12815855
TI  - [Detection and functional role of local gradients of H+-ions on the intracellular
      mitochondrial membrane with covalently linked pH-probe].
AB  - The study is devoted to the registration of local H+ gradients on the inner
      membrane of mitochondria under conditions of H+ pump functioning were recorded.
      By using a covalently linked pH probe (fluorescein isothiocyanate), a local
      increase in the activity of hydrogen ions on the outer face of the inner
      mitochondrial membrane in the presence of the respiration substrate at increased
      permeability of the membrane for K+ was registered. It was also found that the
      buffer capacity of medium affects the respiration rate of completely uncoupled
      mitochondria; a change in respiration rate strictly correlates with changes in
      local H+ gradients on the mitochondrial membrane. It was concluded that local
      gradients of H+ activity can control the rate of functioning of H+ pumps. It was
      shown that, under certain conditions, the system of H+ pumps incorporated into
      succinate oxidase of mitochondria functions as a nonliner system.

PMID- 12815856
TI  - [Possible effect of structural phase transition in the reactive center of
      Rhodobacter sphaeroides on the rate of dark adaptation of photooxidized
      bacteriochlorophyll from primary quinone].
AB  - The dependence of the rate of dark recombination between the photooxidized
      primary donor--dimer bacteriochlorophyll molecule (P) and reduced primary quinone
      acceptor (QA), P+QA(-)-->PQA was studied in photosynthetic reaction centers (RC)
      from Rhodobacter sphaeroides in the temperature range of 100-320 K. Control RC
      preparations, RC species with the removed H-subunit as well as RC samples with
      the hydrogen bonds network modified by isotopic D2O-H2O substitution were
      investigated. An anomalous temperature dependence of the recombination time (tau
      rec) of dark reaction P+QA(-)-->PQA was found for all RC samples. It was found
      that upon heating from 120 to 290 K tau rec increased 2.5 fold. However, upon
      further heating to 320 K, tau rec decreased again. The temperature dependences of
      the P+QA(-)-->PQA recombination time were compared with those of the
      thermodepolarization current of RC preparations in the same temperature range.
      The temperature curve of the thermodepolarization current was also nonmonotonous.
      The theoretical interpretation of the temperature dependence of tau rec as well
      as of the thermodepolarization current was made in the framework of the theory of
      structural phase transitions within the hydrogen bond network in the water
      protein surrounding of the redox centers participating in the electron transfer
      reactions.

PMID- 12815857
TI  - [Effect of low intensity laser light in the red range on macrophage superoxide
      dismutase activity].
AB  - The effect of lipopolysaccharides (LPS) and low-power laser radiation on nitric
      oxide (NO) production and the activity of superoxide dismutase (SOD) in rat
      peritoneal exudate macrophages was investigated. It was found that LPS increased
      NO production and SOD activity in macrophages in a concentration-dependent
      manner. The maximal activity of SOD was more than 100 times greater than in the
      control and was achieved at an LPS concentration of less than 10 ng/ml. The
      maximal production of NO was more than 250% of the control and was achieved at an
      LPS concentration of 100 ng/ml. The presence of cycloheximide, a transcriptional
      synthesis inhibitor, in conditioned media almost completely abolished SOD
      activation and NO production. This implies that the LPS-induced increase in SOD
      activity and NO production were determined by the activation of de novo protein
      synthesis (SOD and inducible NO synthase). The irradiation of macrophages by red
      light resulted in a dose-dependent increase in NO production and SOD activity.
      The incubation of irradiated cells in the presence of 10 microM cycloheximide
      abolished the increase. The presence of antioxidants (mexidol and ascorbate) also
      significantly inhibited the laser-induced activity of macrophages. Thus, laser
      irradiation of cells in the red range activates the synthesis of SOD and
      inducible NO-synthase de novo due to photosensitized initiation of free radical
      reactions.

PMID- 12815858
TI  - [Modeling viability of mammalian cells exposed to ionizing radiation with
      different linear energy transfer].
AB  - A mathematical model of the survival of mammalian cells exposed to ionizing
      radiation is proposed, which takes into account nonuniform radiosensitivity of
      different regions of DNA. The model is based on the assumption that the double
      strand breaks of the anchor DNA, induced either directly by irradiation or by
      enzymes, play a key role in the lethal radiation effect. The model survival
      curves are in good agreement with experimental curves measured in different
      laboratories.

PMID- 12815859
TI  - [Cell membrane electroporator with digital generation of random shaped pulses].
AB  - A Digital Poration System (DPS), a versatile device for electrotreatment of
      biological objects by electric field pulses; was designed, constructed, and
      implemented. A feature distinguishing DPS from the currently available
      electroporators based on capacitor discharge through the load is the use of a
      digital-to-analog converter card as a generator of pulses applied for
      electroporation of biological membranes, with further amplification of the pulse
      by both voltage and current. The shape of pulses, including bipolar pulses, is
      arbitrarily programmable in DPS unlike other electroporators providing
      exponentially decaying and square-wave pulses only. Thus, the application area of
      DPS is substantially extended. In DPS, many of the drawbacks inherent in
      capacitor electroporators are removed, including the need for an additional
      external pulse analyzer monitoring and logging the electroporation processes, the
      necessity to recharge the capacitor before any new pulse, a poor precision of
      setting and measuring the pulse parameters, the need for an additional generator
      of long-lasting low-voltage signals for electrophoresis of ions into the porated
      object, the need for additional AC generators for the alignment of cells before,
      after, and during electroporation, and the need for an additional microprocessor
      to control multi-pulse and/or repetitive protocols. DPS provides a slew rate of
      about 1 V/1 ns required for the electroporation of most mammalian somatic cells,
      with +/- 250 V output voltage and 500 Ohm load resistance. The application area
      of DPS is much wider than for the available porators. It includes
      electrochemotherapy, cell electrofusion, oocyte activation by mimicking calcium
      waves (the latter two are the crucial components of mammalian organism cloning
      technology), dielectrophoretic bunching and orientation ordering of cells,
      sorting of cells, and electrophoresis of charged species into the cells.

PMID- 12815860
TI  - [Phosphorylation of sarcomeric cytoskeletal proteins--an adaptive factor for
      inhibiting the contractile activity of muscle during hibernation].
AB  - The influence of phosphorylation in vitro of the sarcomere cytoskeletal proteins
      titin and X-protein of skeletal muscles as well as C-protein of cardiac muscle of
      ground squirrel Citellus undulatus on the actin-activated ATPase activity of
      myosin and its Ca2+ sensitivity was studied. It was shown that phosphorylation
      lowers the activating effect of titin and C-protein and increases the inhibitory
      effect of X-protein on the enzymatic properties of actomyosin. The
      phosphorylation of the proteins has the most pronounced influence on Ca2+
      sensitivity of actomyosin: it drops to a greater extent in the presence of
      phosphorylated C-protein and titin and is completely inhibited by phosphorylated
      X-protein. The inhibitory influence of phosphorylation in vitro of sarcomere
      cytoskeletal proteins on the above functional properties of the actomyosin system
      as well as the increase in the extent of phosphorylation of titin in vivo upon
      hibernation allow one to conclude that this posttranslation modification
      contributes to adaptive mechanisms of suppression of the contractile ability of
      muscles in this period.

PMID- 12815861
TI  - [Effect of infrared laser radiation on sorption of dry cartilage and connective
      tissue preparations].
AB  - Cartilaginous and connective tissues were exposed to a moderate-intensity IR
      laser treatment with IR radiometric temperature control. The isotherms of water
      sorption by dry preparations of intact and laser-treated tissues were obtained
      and calculated in terms of well known models. It was shown that the sorption
      capacity of a monolayer of tissues decreases with increasing temperature during
      laser treatment. Changes in the supramolecular structure of the extracellular
      matrix of tissues (loss of regularity) upon IR laser exposure are discussed.

PMID- 12815862
TI  - [Effect of low intensity of electromagnetic radiation in the centimeter and
      millimeter range on proliferative and cytotoxic activity of murine spleen
      lymphocytes].
AB  - It was found that single total-body exposure to electromagnetic centimeter waves
      (8.15-18 GHz, 1 microW/cm2, 5 h) stimulated the proliferation of mouse T and B
      splenic lymphocytes. The same effects were observed upon in vivo treatment of
      rats for 5 h with millimeter waves (42.2 GHz, amplitude modulation 10 Hz, 1
      microW/cm2). The whole-body irradiation with centimeter or millimeter waves did
      not cause any significant changes in natural activity of killer cells. The
      cellular responses induced by the irradiation of isolated animal cells in vitro
      did not coincide with those revealed after the total-body irradiation of animals.
      Thus, the in vitro irradiation of natural killer cells to millimeter waves for 1
      h increased their cytotoxic activity whereas, after treatment to centimeter waves
      for the same time, the activity of killer cells did not change. On the contrary,
      irradiation of T and B lymphocytes with millimeter waves (42.2 GHz, amplitude
      modulation 10 Hz, 1 microW/cm2, 1 h) suppressed the blasttransformation of cells.
      The results show a higher immunostimulative potential of centimeter waves as
      compared to millimeter waves.

PMID- 12815863
TI  - [Analytical model of readaptation of the human visual system after light
      exposure].
AB  - The process of readaptation of the human visual system is considered as the
      behavior of a follow-up system, with the brightness of the background being the
      control signal. The times of recovery of visual acuity calculated by the model
      are compared with the experimental data.

PMID- 12815864
TI  - [Problem of identity of functional states of neuronal systems].
AB  - A compartmental conception of modeling the neuron networks is presented.
      Stationary and other regimes under standard electrical stimulation of neuron
      networks are described. Neuron networks may be reducible and irreducible. The
      mathematical model of the stationary state is a model of a normal neuron network
      under hyperventilation. The role of output stimuli in identifying the
      hierarchical structure of neuron networks and the stability of special regimes
      and such structure is discussed. A biological interpretation of the results of
      modeling is presented.

PMID- 12815865
TI  - [Modeling features of induction of long term potentiation in pyramidal neurons in
      the CA3 hippocampal region].
AB  - The conditions for inducing the long-term potentiation in the hippocampus were
      analyzed using the mathematical model of a CA3 pyramidal cell. Their dependence
      on the physiological characteristics of the neuron, the basic biochemical
      processes, and inhibitory efficacy was considered. The role of additional
      membrane depolarization in the origination of the hysteresis of the number of
      phosphorylated receptors as the basis for the formation of an "intermediate"
      stage of long-term potentiation was studied.

PMID- 12815866
TI  - [Pulse flows of neuronal populations of the cerebral cortex exposed to low
      intensity microwaves].
AB  - Pulse flows of populations of cortical neurons in rabbit were investigated prior
      to, during, and after 1-min microwave irradiation (wavelength 37.5 cm, power
      density 0.5-1 mW/cm2). It was found that irradiation caused rearrangements in
      burst activity, which manifested themselves predominantly as changes in the
      number of spikes forming the bursts. The direction of shifts depended on the time
      threshold levels of revelation of bursts. These effects took place during
      microwave irradiation and after its cessation.

PMID- 12815867
TI  - [Effect of geomagnetic activity on the rhythm of resistance of rats to hypoxia].
AB  - The resistance of male Wistar rats to acute hypoxia was estimated from the
      lifetime at an "altitude" of 11.5 km above sea level from 13 to 21 p.m. and in
      different seasons of a year. Identical types of rhythms (circaseptan,
      circasemiseptan, infradian, circadian, and ultradian) of geomagnetic activity and
      lifetime were revealed. It was found that the periods of basal rhythms either
      coincide or are multiple. It was shown that the rhythms of geomagnetic activity
      (including nonbasal rhythms) affect lifetime rhythms (especially ultradian
      rhythms). As the periods of the rhythms decrease, the number of rhythms for both
      parameters increase (ultradian rhythms are most numerous), and relative
      differences in the values of periods (they are minimal for ultradian rhythms) and
      the amplitudes of rhythms decrease.

PMID- 12815868
TI  - [Biophysical basis for principles of universality of speech perception].
AB  - There is increasing evidence that the synergistic interaction of the objectively
      accepted low-frequency rhythm and the subjectively accepted high-frequency sound
      is a source of speech "sense". The lack of one of these components or of their
      synergistic interaction results in the loss of "sense" of the acoustic signal
      being perceived. As for the universality of perception of the sound component of
      speech, there is a model of sound perception, which ensures this universality.
      This model describes the dynamics of audition using the synchronization model of
      oscillations in the Ruell-Takens scenario of transition to chaos. The
      oscillations are described by Hopf bifurcations known to be structurally stable,
      which just provides the universality of sound perception. However, up till now,
      nothing was known about the mechanism of rhythm. It was shown in our study that
      the mechanism of rhythm is described by the Feigenbaum scenario of transition to
      chaos. Upon transition from oscillations to chaos, this scenario incorporates a
      critical point near which the dynamics of the system is described in an universal
      way.

PMID- 12815869
TI  - [Realization of the morphogenetic potential of plants: hormonal-genetic
      approach].
AB  - The basic principles of a model describing the hormonal control of the genome
      expression are stated, and its graphical interpretation is presented. The
      expression and evolution of the genetic information of organisms are regarded as
      an universal process of redifferentiation. The possibility is considered to
      represent the genome as a dynamic system. The study of the morphogenetic
      potential of organisms is based on the approach worked out by E. Cartan to the
      description of dynamic systems. A concept of morphogenetic potential is
      introduced, and its relation to genome states is shown. A mathematical model
      describing the expression of the morphogenetic potential is proposed. The
      mathematical formalism developed can be helpful for the solution of a great
      variety of tasks.

PMID- 12815870
TI  - [Energetic model for formation of cellular mass].
AB  - Based on the law of conservation of energy, a differential equation describing
      changes with time in the mass of a dividing cell was obtained. A mathematical
      expression for the greatest possible value of the mass of an infinitely long
      growing cell that does not enter the process of division was derived. This value
      depends on the correlation between the energy constants characterizing the rate
      of the entrance of substances into the cell and the expenditures for the
      transport of substances inside the cell. A relationship between the time of the
      cell division cycle and these constants was established. For a population of
      dividing cells, the density of their distribution by mass was determined. The
      efficiency of a dividing and a specialized cell was studied. Within the framework
      of the energy approach, possible reasons predetermining the real value of the
      cell mass were considered. A hypothesis was advanced that cell realizes the
      strategy of maximum productivity. It was found that, for this strategy be
      realized, the optimum mass of a parent cell at the end of mitotic division should
      be 39% of its greatest possible value, and that of a specialized cell should be
      29.6% of its respective greatest possible value. Thus, only a third of the energy
      equivalent of the biological mass consumed by both a dividing and a specialized
      cell fall on useful work. Methodical aspects of the experimental verification of
      these results are considered.

PMID- 12815871
TI  - [Screening for abdominal aortic aneurysm--a controversial suggestion].

PMID- 12815872
TI  - [Randomized study of alcohol screening at a surgical emergency unit. Effective
      method for uncovering risky alcohol use--especially in young women].
AB  - This study examined whether alcohol screening identifies a larger percentage of
      patients with hazardous alcohol use compared with standard procedures at a
      surgical emergency unit. Patients were randomised into a study group, where a
      screening procedure was offered, and a control group, where standard procedures
      were followed. In the study group 20.9 per cent (using a conservative estimate,
      14.8 per cent) of the patients screened positive for hazardous alcohol use,
      compared with 6.8 per cent in the control group. The screening procedure was
      particularly effective compared with normal routine in identifying hazardous
      alcohol use among young women.

PMID- 12815873
TI  - [Screening for abdominal aortic aneurysm saves lives at a reasonable cost].
AB  - Ruptured abdominal aortic aneurysms (AAA) cause 600 deaths per year in Sweden. As
      most patients are without symptoms prior to rupture, and about half the patients
      with a ruptured AAA die before arrival to hospital, the only way to reduce
      mortality substantially would be by screening and prophylactic treatment. The
      article reviews experience of screening for AAA from other European countries,
      data from the Swedish vascular registry (Swedvasc) and from the official registry
      of the causes of death in Sweden. With these data as input, a theoretical model
      of inviting all 65-year-old men in Sweden to take part in a screening programme
      for AAA is created. When the programme is fully developed after ten years,
      assuming an attendance rate of 75%, mortality in AAA would decrease from 630 to
      346 per year. The total cost would increase from 154 to 161 million SEK (9 SEK =
      1 Euro). The reason for the relatively minor increase in cost is explained by the
      fact that expensive emergency operations for ruptured AAA decrease by 50%. The
      cost per life saved would be 3,000-4,000 SEK. In conclusion, available data
      suggest that screening for AAA in Sweden would save many lives at a low cost.

PMID- 12815874
TI  - [Psychological stress and musculoskeletal disorders: psychobiological mechanisms.
      Lack of rest and recovery greater problem than workload].
AB  - Psychosocial stress is assumed to contribute to musculoskeletal disorders,
      particularly neck and shoulder pain. Experimental studies show that mental stress
      induces a significant increase in muscle tension in the trapezius muscle and
      several explanatory models have been proposed in order to understand the
      mechanisms linking low sustained muscle tension to musculoskeletal disorders.
      Recently, it has been demonstrated that the same motor units are activated by
      mental stress as by physical demands, which means that mental stress may keep low
      threshold motor units active also during breaks at work and off the job. In the
      modern society, lack of rest and recovery seems even more important for health
      than the magnitude of stress and physical demands during work.

PMID- 12815875
TI  - [Non-allergic rhinitis is surprisingly common. A large variety of conditions can
      cause nasal disorders without simultaneously occurring infection or allergy].

PMID- 12815876
TI  - [Different regions of hippocampus have different roles in learning and memory].

PMID- 12815877
TI  - [Time for a discussion on general principles for screening].

PMID- 12815878
TI  - [Sick listing--"disaster" or incompetence in statistics and diagnostics?].

PMID- 12815879
TI  - [To blame intensive care physicians for shortage of donated organs is pathetic].

PMID- 12815880
TI  - [Tax payers have payed billions for the "blood pressure maffia's" actions].

PMID- 12815881
TI  - [The Swedish Society of Hypertension: cooperation with industry is desirable and
      necessary--with integrity preserved].

PMID- 12815882
TI  - [Irritating advertising campaign concerning onychomycosis].

PMID- 12815883
TI  - [Meagre knowledge about obesity].

PMID- 12815884
TI  - [Study of the causes of recurrence of patients with glottic cancer after partial
      laryngectomy].
AB  - OBJECTIVE: To study the causes of recurrence of patients with glottic cancer
      after partial laryngectomy and to propose some possible measures for the
      prevention of glottic cancer postoperative recurrence. METHOD: A retrospective
      review of consecutive 46 patients with recurrent glottic cancer after partial
      laryngectomy was conducted. The sites of primary tumors, the ways of operations
      and the sites of tumor recurrence were investigated. RESULT: Among 46 patients
      diagnosed with glottic cancer recurrence after partial laryngectomy, 32 cases
      were local recurrences and 14 were regional metastasis or local-regional
      recurrences. 13 cases of the second primary lesions in larynx were the cause of
      the failure and occupied 40.6% of all cases of local recurrences (13/32). In the
      regional metastasis, the commonest recurrent site was encountered in the upper
      neck. The upper neck metastasis or local recurrences were common in local
      recurrent cases treated by salvage surgery. CONCLUSION: It is very important for
      the prevention of glottic cancer recurrence after partial laryngectomy to
      properly manage the upper cervical lymph node in the advanced glottic cancers and
      the local recurrences in larynx and to know the relation of the postoperative
      recurrence of glottic cancer and the second primary lesions in larynx and carry
      out corresponding management.

PMID- 12815885
TI  - [Uni-pedicled sternohyoid myofascial flap reconstruction of the larynx for
      partial laryngectomy].
AB  - OBJECTIVE: To observe the appliance value of uni-pedicled sternohyoid myofascial
      flap in laryngeal function reconstruction after partial laryngectomy. METHOD:
      Forty patients who underwent partial laryngectomy from 1981 to 1999 were
      summarized(male 36 cases, female 4 cases). Among them 19 were supraglottic
      carcinomas (T2N0 6, T2N2 1, T3N0 2, T3N1 1, T3N2 2, T4N0 4, T4N1 1, T4N2 2), 19
      cases were glottic carcinomas(T2N0 6, T3N0 11, T3N2 2), 2 cases were subglottic
      carcinomas(T2N0 1, T3N0 1). The choice of surgical procedure was decided on the
      pathologic conditions of the larynx, the laryngeal function was reconstructed
      using uni-pedicled sternohyoid myofascial flap. RESULT: Thirty-three cases were
      decannulated and recovered with laryngeal functions. The decannulation rate was
      82.50%. All the patients rehabilitated deglutition in 10 to 20 days after
      surgery. None presented complication of aspiration. The 3-year survival rate was
      86.58% and 5-year survival rate was 72.49%. CONCLUSION: The uni-pedicled
      sternohyoid myofascial flaps are appropriate for reconstruction of surgical
      defect in laryngeal carcinomas.

PMID- 12815886
TI  - [Laryngeal function preservation and voice reconstruction in surgical treatment
      of hypopharyngeal and cervical esophageal carcinoma].
AB  - OBJECTIVE: To evaluate surgical treatment methods for preserving laryngeal
      function and voice reconstruction for patients with hypopharyngeal and cervical
      esophageal carcinoma. METHOD: 16 patients with hypopharyngeal and cervical
      esophageal carcinoma were treated with preserving larynx in 8 cases, partial
      laryngectomy with laryngeal reconstruction in 3, voice reconstruction by blom
      singer technique without laryngeal function preservation in 5. The types of
      hypopharyngeal and cervical esophageal reconstruction included gastric
      transpostion, pectoralis major myocutaneous flap, free forearm flap, delto
      pectoral skin flap, sternocleidomastoid myocutaneous flap, platysma myocutaneous
      flap and laryngeal-tracheal flap following carcinoma resection. RESULT:
      Deglutition restored in all patients except one who died of heat-break in 14th
      day after the operation. 13 patients rehabilitated speech, total laryngeal
      function restoration in 6 cases, partial laryngeal function restoration in 2
      cases. The overall following-up was from 2 to 5 years. For the 5 cases with blom
      singer voice reconstruction, all of them restored speech function. CONCLUSION: To
      improve life quality, laryngeal function preservation and voice reconstruction
      should be done for patients with hypopharyngeal and cervical esophageal
      carcinoma. Surgery methods should be carefully selected according to tumor's
      site, staging, patient's general condition and age.

PMID- 12815887
TI  - [A clinical study on improving phonation function of larynx after partial
      laryngectomy].
AB  - OBJECTIVE: To analyse the clinical results of reconstruction of vocal cord using
      sternohyoid muscle flap after partial laryngectomy and research a new repairing
      method to improve laryngeal function and living quality of patient. METHOD: The
      pronunciation of larynx is on the basic of the vibration of the vocal cord by air
      current. The laryngeal appearance and the function of opposite side vocal cord is
      very important for improving the quality of pronunciation. We developed a
      technique of thyroid cartilage membrane and sternohyoid muscle flap to repair the
      defect left by a vertical laryngectomy and reconstructed the vocal cord. The
      thyroid cartilage membrane was used to bridge over the upper part defect of
      laryngeal cavity, the sternohyoid muscle flap forming the opposite side was made
      a 90 degree bent toward the laryngeal cavity to repaired the lower part defect of
      laryngeal cavity and reconstruct a new vocal cord. The repaired larynx recovered
      the normal appearance. The new vocal cord participated speech. The anterior 2/3
      part of both vocal cored could contacted in pronunciation of patient. The
      phonation function of larynx was restored. RESULT: Sixty-one cases partial
      laryngectomy was taken including vertical partial laryngectomy in 37 cases,
      extended vertical partial laryngectomy in 24. During their operations, the
      laryngeal defect was repaired with thyroid cartilage membrane and sternohyoid
      muscle flap, and a vocal cord was reconstructed in the same time. After
      operation, the laryngeal cavity repaired has a normal appearance, and the
      laryngeal satisfactory phonation effect has been obtained. 93.4% of the patients
      enjoyed a socially acceptable voice and rejoined normal working. CONCLUSION: A
      technique of thyroid cartilage and sternohyoid muscle flap to repair the defect
      and reconstructive vocal cord after partial laryngectomy make patient recover
      normal laryngeal appearance and obtain satisfactory phonation effect. Among the
      method of repairation for partial laryngectomy sternohyoid muscle flap should be
      first considered owing to its various merits: 1. abundant material. 2. convenient
      procedures. 3. smaller trauma. 4. satisfactory effect.

PMID- 12815888
TI  - [One stage reconstruction of larynx and cervical trachea involved by advanced
      thyroid carcinoma].
AB  - OBJECTIVE: To investigate clinical prognosis and the one-stage methods of
      reconstruction for advanced thyroid carcinoma while larynx and cervical trachea
      involved. METHOD: One-stage resection and laryngotracheal reconstruction were
      performed in 18 advanced thyroid carcinomas. Among them, total laryngectomy were
      performed in 3 cases and partial laryngectomy in the other 4 larynx-involved
      cases. Cervical trachea involvement were found in all 18 cases. Besides 8 shave
      off of tumor, area of trachea invaded by carcinoma were removed in other 10
      cases. The methods applied for the tracheal reconstruction were 1 simple suture,
      3 tracheal anastomosis, 2 pedicled sternocleidomastoid myoperiosteous flap, 3
      insular myocutaneous pectoralis major flap and 1 cervical flap. RESULT: One
      patient died of cancer reoccurrence while in the hospitalization. Except for 3
      cases with total laryngectomy, larynx preservation were done in 14 cases and
      tracheal cannula were pulled out in 8, blocked in 2 and kept carrying in 4 cases.
      CONCLUSION: One stage reconstruction of larynx and cervical trachea involved by
      advanced thyroid carcinoma is feasible and practical. Curative rate, survival
      time and life quality all can be improved.

PMID- 12815889
TI  - [An analytical study and report on 23 cases of neurolemmoma in the head and
      neck].
AB  - OBJECTIVE: To improve the understanding of the diagnosis and treatment of
      neurolemmoma in the head and neck by exploring its clinical features. METHOD:
      Among all cases treated surgically, 15 cases of neurolemmoma in the neck were by
      the approach of lateral pharyngotomy, one case of neurolemmoma in the nasal
      cavity by lateral rhinotomy, three cases by mouth. Two cases of facial
      neurolemmoma were resected by the combined approach (mastoid process, middle
      cranial fossa and posterior cranial fossa) and radical mastoidectomy
      respectively. One case of neurolemmoma in the pyriform sinus was completely
      removed by the forceps under esophagoscope. One case of neurolemmoma in the
      trachea was removed by tracheotomy. RESULT: Twenty cases were followed up from 3
      months to 7 years and 19 cases did not recur. One case of neurolemmoma in the
      nasal cavity and sinus recured 3 years after operation. One case developed
      Horner's syndrome postoperatively and disappeared after two months. One case
      developed hoarseness. CONCLUSION: It is difficult to diagnose neurolemmoma before
      operation. Diagnosis of the disease is based on pathological examination.
      Resection of the tumor should be performed as soon as possible under careful
      protection of the function of the nerve in order to avoid severe complications.

PMID- 12815890
TI  - [Predictive value of sleep nasendoscopy and the Muller maneuver in
      uvulopalatopharyngoplasty for the obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To improve the therapy effect of uvulopalatopharyngoplasty (UPPP) for
      the obstructive sleep apnea syndrome (OSAS) with the use of sleep
      pharyngolaryngoscopy and the Muller maneuver to localize pharyngeal airway
      collapse. METHOD: Twenty-eight patients with OSAS were divided into two groups
      respectively based on findings of Muller maneuver and sleep pharyngolaryngoscopy:
      Type I had only oropharyngeal(soft palate and palatine tonsil) collapse and type
      II had oropharyngeal collapse with hypopharyngeal collapse. All outcome of PSG
      after UPPP was analyzed. RESULT: 1. In Type I, the change of the average apnea
      hypopnea index (AHI) and the lowest SaO2 before and after UPPP was 52.7 to 19.7
      (P < 0.01), 63.1% to 80.0% (P < 0.01) using Muller maneuver, and 48.6 to 18.7(P <
      0.01), 65% to 80%(P < 0.01) using sleep pharyngolaryngoscopy respectively; In
      type II, the change was respectively 54.7 to 38.6(P > 0.05), 60.7% to 67.0%(P >
      0.05) using Muller maneuver, and 59 to 34(P < 0.01), 59% to 71%(P < 0.05) using
      sleep pharyngolaryngoscopy. 2. Surgical response rate in type I was compared with
      type II: 68.4% VS 22.2% (P < 0.01) using Muller maneuver and 73.3% VS 30.8% (P <
      0.05) using sleep pharyngolaryngoscopy, respectively. CONCLUSION: Endoscopic
      pharyngeal assessment of OSAS patients has clinical value for the improvement of
      UPPP outcome.

PMID- 12815891
TI  - [The complications of reoperation for thyroid disease after a thyroidectomy].
AB  - OBJECTIVE: To find out the morbidity of reoperation for thyroid disease, and
      discuss its complications and the risk factors associated with it. METHOD:
      Retrospective study. Incidence of recurrent laryngeal nerve palsy and
      hypoparathyroidism. This paper reported 43 cases underwent secondary
      thyroidectomy during the year from 1997 to 2001 in our hospital. Frozen sections
      were done in all cases during the operations. RESULT: Of the 43 cases, the
      initial frozen sections pathologic diagnosis were benign diseases in 30 cases,
      but their last pathologic diagnosis were malignant change after the first
      operation. Complications were 6 transient palsy of the recurrent laryngeal nerve,
      2 patients developed permanent unilateral palsy and one temporary
      hypoparathyroidism. CONCLUSION: Frozen section helps to raise the accuracy of
      diagnosis. Secondary thyroidectomy can be avoided by selecting suitable types of
      operations. Subtotal thyroidectomy of benign nodular thyroid will be good for
      preventing recurrence. Secondary thyroidectomy should be safe procedure. Because
      of the high risk of complications reoperations for thyroid gland disease should
      be done only if the patient cannot be treated in other ways.

PMID- 12815892
TI  - [Surgery of substernal thyroid goiter: 32 cases reported].
AB  - OBJECTIVE: To probe into the surgical approaches and operative techniques for
      substernal thyroid goiter. METHOD: In the way with operating on thyroid
      retrosternal thyroid tumour were removed via cervical collar incision and
      substernal thyroid cancer was partly removed via "perpendicular" shape cervical
      incision and tracheotomy. RESULT: The operations via cervical collar incision on
      31 cases with substernal thyroid goiter have been carried out successfully. One
      thyroid cancer was partly moved via "perpendicular" shape cervical incision and
      tracheotomy, radiation therapy and isotope was adopted after operation, the
      patient survived above 5 years. Syndrome occurred in 9 cases (28.1%); recurrent
      laryngeal nerve were damaged in 5(15.6%), hemorrhage in 3(9.4%). CONCLUSION:
      Resection via cervical collar incision for all retrosternal thyroid nodules was
      advised and surgery for malignancy needs to be investigated.

PMID- 12815893
TI  - [Treatment of hypopharyngeal stricture after total laryngectomy by interventional
      therapy with inner-cavity cradle].
AB  - OBJECTIVE: To investigate the main factors in the treatment of hypopharyngeal
      stricture after total laryngectomy by interventional therapy with inner-cavity
      cradle. METHOD: Nine patients of hypopharyngeal stricture after total
      laryngectomy accepted the interventional therapy with inner-cavity cradle.
      RESULT: The interventional therapy with inner-cavity cradle succeeded in 8
      patients, the difficulty of swallowing was obviously improved immediately after
      the therapy. The therapy failed in 1 patient. The follow-up period lasted from 5
      months to 36 months. For the 8 patients, the inner-cavity cradle helped them to
      overcome the difficulty of swallowing, gained more time for further treatment.
      CONCLUSION: A suitable inner-cavity cradle can extend the hypopharyngeal
      stricture after total laryngectomy, help the patient to overcome the difficulty
      of swallowing. The therapy is easy to perform, the effect is reliable. It can be
      a utility treatment for the hypopharyngeal stricture.

PMID- 12815894
TI  - [Newborn tracheotomy without tracheal intubation].
AB  - OBJECTIVE: To approach the tracheotomy in newborn without tracheal intubation in
      emergency. METHOD: Five cases hospitalized between March 1998 and March 2002 were
      reviewed retrospectively. The mean age was 19 days from 5 hours to 24 days after
      born. All patients accepted the operation without tube insertion in trachea
      because of the primary disease. RESULT: The operation was performed successfully
      in all cases. One case died of severe respiratory and circulatory failure. Four
      cases were decannulated with the primary disease cured. CONCLUSION: Preoperative
      evaluation and ideal timing of tracheotomy are very important for the newborn
      infant. Intensive postoperation nursing are recommended.

PMID- 12815896
TI  - [Obstructive sleep apnea syndrome: an analysis of treatment in 450 patients].
AB  - OBJECTIVE: To explore the most appropriate treatment through comparing surgery,
      coblator plasma surgery (CPS) and nasal continuous positive airway pressure
      (nCPAP) in obstructive sleep apnea syndrome (OSAS). METHOD: Four hundred and
      fifty cases were retrospectively analyzed, 368 patients were operated by
      uvuloplatopharyngoplasty (UPPP), partial excision of root of tongue and/or
      partial inferior turbinectomy. CPS were performed in 65 patients and 25 cases
      were accepted the nCPAP. Among them, 17 were the first selection and 8 were the
      second selection after operation failure. RESULT: The outcomes of near-term (3-6
      months) and long-term (1-3 years) in CPAP group are 95.23% and 83.33%, higher
      than surgery and CPS group. In the near-term result, surgery group is similar to
      CPS group (86.39% and 78.04%). The long-term effective of surgery group is lower
      than 50% and become worse with the time passed. And surgery may be accompanied
      with some dangerous and complications after operation. But the side effect in CPS
      and nCPAP is very little. CONCLUSION: The treatment of OSAS is developing to
      safety, simple and acceptable. nCPAP and some simple safely surgery are fitted in
      serious patients. UPPP, CPS and nCPAP have good effect in light and middle
      patients. The long-term effect of CPS should still be observed in future.

PMID- 12815895
TI  - [The ex vivo expansion of gamma delta T cells from the peripheral blood of
      patients with nasopharyngeal carcinoma and their cytotoxicity to nasopharyngeal
      carcinoma lines in vitro].
AB  - OBJECTIVE: gamma delta T cells from the peripheral blood of nasopharyngeal
      carcinoma(NPC) patients were expanded in vitro and their cytotoxic activity to
      NPC lines was analysed. A role of gamma delta T cell of immune mechanism in
      development of NPC was discussed. METHOD: The solid-phase monoclonal anti-TCR
      gamma delta McAb was used to expand the gamma delta T cells from peripheral blood
      of seven patients with NPC and six healthy donors. Then we detected the
      cytotoxicities of these gamma delta T cell against tumour cell lines including
      Daudi Burkitt's lymphoma and the cell lines of NPC, CNE1 and CNE2, at different
      effector:target (E:T) ratio by MTT method. The immunophenotyping of gamma delta T
      cells was detected by flow cytometry. RESULT: gamma delta T cell were obtained
      with a high purity (> 82%) from healthy individuals and NPC patients in which 90%
      of expanded cells were V gamma 9/V delta 2 subtype. The results of cytotoxicity
      assays revealed that activated gamma delta T cells from both healthy donors and
      patients lysed Daudi, CNE1 and CNE2 cells at similar level(P > 0.05) when E:T
      ratios increased, the level of cytotoxicity to each of the targets of CNE1 and
      CNE2 increased. These gamma delta T cells exhibited highest level of cytotoxicity
      to the Daudi cells in same ration of effector to target cell. CONCLUSION: gamma
      delta T cell of NPC could significantly kill NPC in vitro.

PMID- 12815897
TI  - [Significance of p53, c-myc and nm23 protein expression in recurrent laryngeal
      carcinoma].
AB  - OBJECTIVE: To evaluate the prognosis of postoperative laryngeal cancer
      recurrence, the study was designed to investigate the relationship of p53, c-myc
      and nm23 protein expression in recurrent laryngeal carcinoma. METHOD: Five
      hundred and seventy-four cases of laryngeal carcinoma were retrospectively
      reviewed. All the patients were observed for 3 years postoperatively, 56 cases
      with recurrence were diagnosed and 39 cases of normal laryngeal tissue were
      compared. The tissue microarrays was made in all the cases. The tissue chip was
      analyzed by the SABC immunohistochemical method. RESULT: p53, c-myc and nm23
      expressed in most of the laryngeal carcinoma. The positive ratio is different.
      There is higher expression of c-myc in recurrent laryngeal carcinoma, and its
      expression has significant difference with the laryngeal carcinoma, which have no
      recurrence (P < 0.01). nm23 has lower expression in recurrent laryngeal
      carcinoma, and it's expression has significant difference with the laryngeal
      carcinoma which have no recurrence(P < 0.01). The expression of p53 has no
      significant difference between recurrent laryngeal carcinoma and the laryngeal
      carcinoma which have no recurrence(P > 0.05). There is the positive correlation
      between the expression of c-myc and the recurrent laryngeal carcinoma; and
      negative correlation between the expression of nm23 and the recurrent laryngeal
      carcinoma. CONCLUSION: c-myc and nm23 could be the prognosis marker of
      postoperative laryngeal cancer recurrence.

PMID- 12815898
TI  - [The expression of CD44 and it's significance in human laryngeal carcinoma].
AB  - OBJECTIVE: To explore the CD44 expression in different laryngeal carcinoma
      tissues and their clinical significance. METHOD: Using immunohistochemistry
      methods to study 261 cases of archived paraffin-embedded laryngeal tissue.
      RESULT: The results turned out to be as follows: 1. A high level of CD44
      expression was more frequently found in laryngeal carcinoma than in precarcinoma
      lesions and normal tissues. 2. CD44 expression correlated well with histological
      grades, the higher grade the lower the CD44 expression. 3. The third and fourth
      stages laryngeal carcinoma had stronger CD44 positive than those of the first and
      second stages. 4. CD44 expression in laryngeal carcinoma with cervical metastasis
      were higher than those without cervical metastasis. 5. To 3 and 5 years survival,
      CD44 positive cases had lower chance than CD44 negative cases. CONCLUSION: These
      results implicates that the occurrence, development and prognosis of laryngeal
      carcinoma may be closely related to CD44 expression.

PMID- 12815899
TI  - [The expression of extracellular matrix in squamous cell carcinoma of the larynx:
      an immunohistochemical study].
AB  - OBJECTIVE: To investigate the expression and the protective significance of
      extracellular matrix (ECM) in laryngeal squamous cell carcinomas(LSCC). METHOD:
      The expression and distribution of three antigens, human type IV collagen(CT IV),
      laminin(LN) and fibronectin(FN) were immunohistochemically determined in 72 cases
      of LSCC by using the corresponding monoclonal antibodies. The correlation of the
      intact continuance of ECM around the tumor nest with the cell differentiation,
      invasion mode and the regional lymph node metastasis of laryngeal squamous cell
      carcinoma was evaluated. RESULT: In cases with poor histological differentiation,
      the defect of ECM was more severe than that in cases with high or middle
      histological differentiation(P < 0.01). Moreover, cases with diffuse invasion
      revealed lower ECM expression compared with cases with better tumor-host border
      (P < 0.01). There was a higher risk of regional lymph node metastasis among cases
      with poor ECM expression (P < 0.01). And there was a significant association
      between the defect of ECM and the lymph node metastasis(P < 0.01). CONCLUSION:
      These observations indicates that testing the distribution and the expression of
      ECM seems to be useful to evaluate the histological grading of malignancy and the
      invasion mode of laryngeal squamous cell carcinoma and to be helpful to
      prognosticate the frequency of regional lymph node metastasis.

PMID- 12815900
TI  - Culture-based group B streptococcal screening. Adherence to current guidelines.
AB  - OBJECTIVE: To examine the ability of a universal screening strategy to identify
      and treat group B Streptococcus-positive women with intrapartum antibiotics.
      STUDY DESIGN: Charts were reviewed on all patients delivering at > or = 36 weeks
      of gestation as to the presence of culture results, whether or not antibiotics
      were ordered and when they were given relative to the time of delivery. RESULTS:
      Approximately 95% of patients presenting at > or = 36 weeks had group B
      Streptococcus results available. Overall, 84% of culture-positive patients
      received chemoprophylaxis. Removal of the elective cesareans from the study
      population increased the percentage of positive patients receiving antibiotics to
      94%. Ideal chemoprophylaxis, defined as delivering > or = 2 hours after receiving
      the recommended antibiotics, occurred 87% of the time. Failure to order
      appropriate antibiotics was the most frequent reason for not receiving
      chemoprophylaxis. CONCLUSION: Successful universal culturing followed by
      intrapartum chemoprophylaxis can be accomplished in a majority of cases. Failure
      to treat can occur (6%), and chemoprophylaxis may be less than ideal (13%) due to
      rapid labor and human error.

PMID- 12815901
TI  - Vulvar carcinoma associated with lichen sclerosus. Experience at the Florence,
      Italy, Vulvar Clinic.
AB  - OBJECTIVE: To compare demographic and clinical characteristics of patients with
      lichen sclerosus (LS)-associated squamous cell carcinoma (SCC) of the vulva with
      those of patients with tumors not histologically associated with LS in a series
      of patients with vulvar SCC not HPV correlated. STUDY DESIGN: We retrospectively
      reviewed histologic specimens and clinical files of all vulvar SCCs referred to
      the Vulvar Clinic, University of Florence, Florence, Italy, since 1990. RESULTS:
      Twenty-five out of the 72 cases in this study (34.7%) were LS associated. Among
      these cases, 8 (32%) were diagnosed with LS before occurrence of the cancer and
      received treatment for the disease. In 17 cases the diagnosis of LS was
      simultaneous with that of SCC; in 13 cases the diagnosis was achieved by clinical
      examination and confirmed afterwards histologically. In 4 cases this was
      confirmed only by means of histologic examination. The shared profile of patients
      with LS-associated vulvar SCC was a subject (mean age, 72 years) seldom with a
      past medical history of vitiligo (16% of cases), with invasive cancer (92% of
      cases), clinically characterized by an exophitic tumor (73%), seldom ulcerated
      (18%) or showing hyperkeratosis (9%). Labia majora (32%), labia minora (27%) and
      vestibule (23%) were the most frequently involved sites. In most cases (80%) the
      cancer was limited to 1/3 of the vulvar region. An itch was the most frequent
      symptom. However, for all of these variables, no overall statistically
      significant difference was found with patients who had SCCs not associated with
      LS. CONCLUSION: The experience of the Vulvar Clinic, University of Florence,
      confirms the suggested role of LS as a possible precursor of vulvar carcinoma
      since 32% of our cases not HPV related were LS associated. We demonstrated that
      the profile of patients with LS-associated cancer does not differ from that of
      patients with cancer not associated with LS, excluding HPV-related cases. The
      existence of accessory conditions, probably needed to promote the progression
      from LS to cancer in a minority of subjects remains to be established.

PMID- 12815902
TI  - Comparison of cryopreserved sperm in vaporous and liquid nitrogen.
AB  - OBJECTIVE: To evaluate the feasibility of using the vaporous phase of liquid
      nitrogen as a storage medium for human semen samples. STUDY DESIGN: Human semen
      samples were used in a 2-armed study. In the first arm, semen samples were
      rapidly frozen and randomly assigned to storage in either liquid nitrogen (-196
      degrees C) or vapor-phase nitrogen (-189 degrees C). In the second arm, sperm
      specimens were frozen in a controlled, stepwise process and randomly assigned to
      storage in either the vaporous or liquid phase of liquid nitrogen. The samples
      were subsequently thawed and analyzed for sperm viability. RESULTS: The rapid
      freezing technique demonstrated no differences in the examined viability
      parameters between semen specimens stored in either liquid or vaporous nitrogen.
      Similarly, semen samples prepared by the slower, controlled freezing process also
      showed no differences in viability parameters after storage in either the liquid
      or vaporous phase of liquid nitrogen. The rapid freezing technique was equal to
      the slow, controlled freezing method in terms of preserving the integrity of the
      sperm when the specimens were subsequently stored in either liquid or vaporous
      nitrogen. CONCLUSION: Cryopreservation of human semen in the vapor phase of
      nitrogen is a viable alternative to storage in liquid-phase nitrogen.

PMID- 12815903
TI  - Measuring uterine depth with colpohydrosonography.
AB  - OBJECTIVE: To evaluate the accuracy of colpohydrosonography for measuring uterine
      depth. STUDY DESIGN: Uterine depth was assessed in 64 women being evaluated for
      assisted reproductive technology treatment in a high-volume private practice.
      After noting the cavity depth by standard transvaginal ultrasonography, a small
      amount of saline (10-20 mL) was instilled into the vagina, and the uterine depth
      was remeasured. The results were compared to the depth measured by mechanical
      sounding performed during a different evaluation. The sonographic measurements of
      uterine cavity depth were correlated with mechanical sounding. RESULTS:
      Colpohydrosonography correlated strongly with uterine depth as measured by
      mechanical sounding (r = .89), while standard vaginal ultrasound correlated less
      well with sounding (r = .66). There was < 5% difference between
      colpohydrosonography and mechanical sounding in 89% of patients, while 48% of
      standard vaginal ultrasounds varied from sounding by > 10%. CONCLUSION:
      Colpohydrosonography is a simple procedure that more accurately measures uterine
      cavity depth than conventional transvaginal ultrasound alone. Improved precision
      of cavity depth measurement could have implications for improving embryo
      placement during assisted reproductive technology treatment.

PMID- 12815904
TI  - Lecithin/sphingomyelin ratio and lamellar body count. What values predict the
      presence of phosphatidylglycerol?
AB  - OBJECTIVE: To assess which values of the lecithin/sphingomyelin (L/S) ratio and
      lamellar body count (LBC) optimally correspond to the presence of
      phosphatidylglycerol (PG). STUDY DESIGN: A database of clear amniotic fluid
      specimens obtained by amniocentesis was accessed. Receiver operating
      characteristic curve analysis was performed for both L/S ratio and LBC to
      identify the optimal thresholds for predicting the presence of PG. RESULTS: One
      hundred eighty-eight patients were included in the analysis. "Trace" PG was more
      like "absent" PG in relation to both L/S ratio and LBC. There were significant
      relationships between L/S ratios and presence of PG (area under the curve = .909,
      P < .0001) and between LBC and presence of PG (area under the curve = .94, P <
      .0001). The positive predictive value of L/S ratio > 2 was 76%, and that of LBC >
      30,000 was 82% in predicting the presence of PG. Optimal threshold values for the
      prediction of PG presence were > 3.0 for L/S ratio, which had a positive
      predictive value of 95% and false positive rate of 5%, and > 50,000 for LBC, with
      a 96% positive predictive value and 5% false positive rate. CONCLUSION: "Mature"
      results for PG in amniotic fluid are equivalent to an L/S ratio of > 3.0 and LBC
      > 50,000 and help explain the later gestational age at the appearance of lung
      maturity by PG than by L/S > 2 or LBC > 30,000.

PMID- 12815905
TI  - Effect of maternal height on gestational age and birth weight in nulliparous
      mothers of triplets with a normal pregravid body mass index.
AB  - OBJECTIVE: To study the effect of maternal height on gestational age and birth
      weight of triplets born to nulliparous women with a normal pregravid body mass
      index (BMI). STUDY DESIGN: A 1988-2000 prospective cohort of 1,219 U.S. live-born
      triplets was evaluated. Patients were grouped into stature categories of 5-cm
      intervals. Mean values for BMI, height, maternal age, gestational age at birth,
      total triplet birth weight and frequencies of births at < 28 weeks and with very
      low birth weight were calculated for each height category. RESULTS: Maternal
      heights were normally distributed (mean, 165.2 +/- 6.2 cm). We found a
      significant positive correlation (R2 = .95), different from a zero slope (P <
      .01), between mean total triplet birth weight and height category. Nulliparous
      women who were taller than 165 cm had age, BMI and gestational age
      characteristics similar to those of their shorter counterparts but delivered
      significantly heavier triplets and were at significantly lower risk of delivering
      very-low-birth-weight triplets. CONCLUSION: Taller women are more likely to
      deliver heavier triplets and are at lower risk of delivering very-low-birth
      weight triplets. This information should be included in counseling women with the
      potential of conceiving triplets.

PMID- 12815906
TI  - Detecting fetal macrosomia with abdominal circumference alone.
AB  - OBJECTIVE: To determine if abdominal circumference (AC) can identify macrosomia
      (> or = 4,000 g) at or beyond 37 weeks. STUDY DESIGN: Prospectively, parturients
      at term admitted for delivery underwent sonographic mensuration of AC. A receiver
      operating characteristic (ROC) curve was constructed to determine if AC can
      differentiate between normal (birth weight < 3,999 g) and macrosomia. A
      likelihood ratio was calculated. P < .05 was considered significant. RESULTS: The
      mean gestational age of the 256 subjects was 39.1 +/- 1.5 weeks, and the
      prevalence of macrosomia was 8.2% (21/256). Inspection of the ROC curve indicated
      that AC > or = 350 mm can identify macrosomic fetuses. The area under the ROC
      curve (0.79 +/- 0.04 for macrosomia) was significantly different than the area
      under the nondiagnostic line (P < .005). The likelihood ratio for AC to detect
      macrosomia was 2.9 (95% confidence interval, 2.1-4.0). Based on the proportion of
      macrosomia in our population, we would require over 1,000,000 newborns for a
      macrosomia analysis to obtain narrow confidence intervals around a clinically
      useful likelihood ratio. CONCLUSION: Using the guidelines proposed by the
      Evidence-Based Medicine Working Group, AC is slightly useful in detecting
      macrosomia among term parturients.

PMID- 12815907
TI  - Perinatal hospice. Comprehensive care for the family of the fetus with a lethal
      condition.
AB  - OBJECTIVE: To describe our experience in providing a program of structured
      interdisciplinary care for the families of fetuses prenatally diagnosed with a
      lethal congenital anomaly. STUDY DESIGN: We developed a comprehensive "perinatal
      hospice" program for the supportive care of families with fetuses known to have a
      lethal condition. Upon prenatal diagnosis of a lethal fetal condition, parents
      were presented with the option of elective pregnancy termination versus a multi
      disciplinary program of ongoing supportive care until the time of spontaneous
      labor or until delivery was required for obstetric indications. We evaluated
      patient use of this new service and the natural history of pregnancies managed in
      this fashion. RESULTS: The population consisted of 33 patients carrying a fetus
      with a clearly delineated lethal anomaly. Twenty-eight (85%) chose to participate
      in the perinatal hospice program. Of these, 11/28 (39%) had an intrauterine fetal
      death and 17/28 (61%) delivered a live-born infant. Among the live-born infants
      were 12 vaginal deliveries, 4 preterm and 8 at term. Obstetric indications or
      maternal request resulted in cesarean delivery for 5/28 (18%), 4 preterm and 1 at
      term, all live born. All live-born infants died within 20 minutes to 2 months.
      There were no maternal complications. CONCLUSION: The availability of a
      structured program providing ongoing, comprehensive, multidisciplinary,
      supportive perinatal care offers a tangible and safe alternative to early
      elective pregnancy termination for patients carrying a fetus with a lethal
      congenital condition.

PMID- 12815909
TI  - Synchronous expression of pinopodes and alpha v beta 3 and alpha 4 beta 1
      integrins in the endometrial surface epithelium of normally menstruating women
      during the implantation window.
AB  - OBJECTIVE: To use histology, scanning electron microscopy (SEM) and
      immunohistochemistry to examine the expression of pinopodes, and alpha v beta 3
      and alpha 4 beta 1 integrins in the same endometrial biopsies. STUDY DESIGN: A
      prospective observational study. Fifteen consecutive regularly menstruating women
      with normal hormone profiles were followed for detection of ovulation and then
      biopsied twice, on postovulatory days luteinizing hormone (LH) +6 and LH +8.
      Measurements included abundance and development stage of pinopodes and a
      semiquantitative assessment of intensity of antibody staining for integrins.
      RESULTS: All biopsies observed under light microscopy showed an in-phase
      endometrium. Pinopodes were found developing mostly on day LH +6 and were fully
      developed on day LH +8. The expression of alpha v beta 3 dimer increased
      significantly from day LH +6 to day LH +8, while alpha 4 beta 1 dimer did not
      show any significant change during the same period. Fully developed pinopodes and
      strong intensity of alpha v beta 3 integrin were the most common findings.
      CONCLUSION: These results indicate a coordinated, synchronous change in
      morphology and adhesion molecule expression of endometrial epithelial cells on
      day LH +8 of a normal menstrual cycle.

PMID- 12815908
TI  - Outcome of intracytoplasmic injection of fresh and frozen-thawed testicular
      spermatozoa. A comparative study.
AB  - OBJECTIVE: To compare the outcomes of intracytoplasmic sperm injection (ICSI)
      with fresh and cryopreserved testicular spermatozoa in patients with obstructive
      and nonobstructive azoospermia. STUDY DESIGN: Retrospective analysis. RESULTS: A
      total of 60 ICSI treatment cycles (32 fresh, 28 frozen) using testicular sperm
      obtained by open biopsy were analyzed retrospectively. No statistically
      significant differences were noted in any of the parameters examined between ICSI
      cycles from fresh and frozen-thawed testicular spermatozoa. Fertilization rates
      were 61.9% with fresh vs. 61.7% with frozen-thawed testicular sperm, pregnancy
      rates per embryo transfer 29.1% vs. 25.0%, respectively, and delivery rates 85.7%
      vs. 80.0%, respectively. CONCLUSION: Intracytoplasmic sperm injection with frozen
      thawed testicular spermatozoa permits the obtaining of satisfactory fertilization
      and pregnancy rates, and the cryopreserved sperm can be used as an effective
      sperm source in future ICSI cycles.

PMID- 12815910
TI  - High prevalence of mullerian anomalies diagnosed by ultrasound in women with
      polycystic ovaries.
AB  - OBJECTIVE: To determine, with a case-control study, if polycystic ovaries are
      associated with a higher rate of uterine mullerian anomalies. STUDY DESIGN: A
      total of 214 women were included. Transvaginal ultrasonography of the ovaries and
      the uterus was performed in all. The women were divided into 2 groups, a group
      with polycystic ovaries (n = 120) and another with normal ones (n = 94). RESULTS:
      Women with polycystic ovaries had a higher rate of uterine mullerian anomalies.
      In the polycystic ovary group, 53 (44.2%) had uterine mullerian anomalies; 17
      (18.1%) were found in the normal ovary group (P < .0001). CONCLUSION: There is an
      association between polycystic ovaries and high rate of uterine mullerian
      anomalies.

PMID- 12815911
TI  - Pronuclear scoring. Time for international standardization.
AB  - Zygote scoring is an efficient tool for embryo selection not only in countries
      where embryo selection is not permitted. Several different scoring systems have
      been published so far, making comparisons of assessments between investigators
      and laboratories extremely difficult. Pronuclear evaluation should be
      standardized in a manner analogous to the standardization of cleavage stage
      embryo scoring or of semen evaluation by the World Health Organization. The ideal
      score should be clear and easily applicable. The items that have the greatest
      influence on embryonic development seem to be alignment and size of pronuclei,
      alignment and number of nucleoli, halo effect and appearance of vacuoles. These
      morphologic parameters can be observed in different features and can be
      summarized as a zygote score.

PMID- 12815912
TI  - Effectiveness of 2-step (consecutive) embryo transfer. Comparison with cleavage
      stage transfer.
AB  - OBJECTIVE: To evaluate the effectiveness of 2-step (consecutive) embryo transfer
      (ET), in which two cleaved embryos are transferred on day 2 (first step of ET)
      and a single blastocyst is transferred on day 5 (second step of ET) in comparison
      with conventional day 2 ET. STUDY DESIGN: Observational comparative study at
      different time periods. Subjects were those who had > or = 4 embryos on day 2
      after oocyte retrieval. Those in the conventional group (n = 60) received
      conventional day 2 ET, in which 3 cleaved embryos were transferred on day 2
      between January 1999 and June 2000. Those in the 2-step group (n = 124) received
      2-step embryo transfer, in which 2 cleaved embryos were transferred on day 2 and
      a blastocyst was transferred on day 5 between September 2000 and February 2002.
      Patients who planned to receive 2-step ET but could not proceed to the second
      step of ET because of failure to produce blastocysts were included in the 2-step
      group. RESULTS: The ongoing pregnancy rate with 2-step ET (51.6%) was
      significantly higher than with conventional ET (26.7%) (P < .01). The clinical
      pregnancy rate and implantation rate in conventional and 2-step ET were 30.0% vs.
      59.7% and 11.1% vs. 27.8%, respectively (P < .001). CONCLUSION: Two-step ET may
      benefit patients who can obtain a sufficient number of embryos.

PMID- 12815913
TI  - Cognitive function variations in postmenopausal women treated with continuous,
      combined HRT or tibolone. A comparison.
AB  - OBJECTIVE: To compare cognitive function in postmenopausal women receiving
      continuous hormone replacement therapy and those receiving tibolone. STUDY
      DESIGN: This was a 6-month, prospective, single-blind, single center, randomized
      study. A total of 50 healthy, postmenopausal women were enrolled. In the end, 40
      women completed the 6-month follow-up. One group (23 subjects) received
      conjugated equine estrogens (CEE), 0.625 mg/d, and medroxyprogesterone acetate
      (MPA), 5 mg/d. The other group (17 subjects) received tibolone, 2.5 mg/d. Their
      serum estradiol levels and Cognitive Abilities Screening Instrument (CASI) and
      Mini-Mental State Examination (MMSE) scores were obtained before starting and
      after 3 and 6 months of treatment. RESULTS: There was a significant increase in
      the serum estradiol level in the CEE + MPA group, especially after 3 months of
      treatment, but there was no increase in the estradiol level in the tibolone
      group. The CASI and MMSE scores of the CEE + MPA group and the tibolone group
      after 3 and 6 months of treatment showed no significant difference between the
      two groups apart from the MMSE at the 3-month follow-up. We saw an increasing
      trend in CASI and MMSE scores after treatment in both groups; however, the
      increases were not statistically significant. The rate of increase of both CASI
      and MMSE scores in the CEE + MPA group was greater than in the tibolone group,
      though the difference was not significant. CONCLUSION: This preliminary study
      demonstrated that both CEE + MPA and tibolone can preserve cognitive function and
      may be able to prevent cognitive decline in postmenopausal women during short
      term treatment. Our results also show that continuous, combined CEE + MPA seems
      to be marginally more effective than tibolone in improving cognitive processes;
      however, long-term study is needed to follow-up such effect.

PMID- 12815914
TI  - Diagnosis of a small, androgenizing Brenner cell tumor in a postmenopausal woman
      aided by laparoscopic salpingo-oophorectomy. A case report.
AB  - BACKGROUND: Rapidly progressive hirsutism or virilization in the postmenopausal
      woman raises the suspicion of an androgen-secreting tumor. Hormonal testing and
      imaging studies usually rule out an adrenal tumor. However, small, androgenizing
      ovarian tumors may not be detectable by imaging studies. CASE: A postmenopausal
      woman presented with rapidly progressive hirsutism and elevated androgens.
      Imaging studies did not localize the tumor. Bilateral laparoscopic oophorectomy
      was performed, and a small, androgenizing Brenner cell tumor of the left ovary
      was demonstrated on histologic examination. CONCLUSION: Because of the low
      morbidity associated with laparoscopic salpingo-oophorectomy, it may be
      reasonable to remove the ovaries of postmenopausal women who display virilization
      or rapidly progressive hirsutism and elevated androgens, even if imaging studies
      do not detect the ovarian tumor.

PMID- 12815915
TI  - Transvaginal uterine artery ligation in a woman with uterine leiomyomas. A case
      report.
AB  - BACKGROUND: Uterine artery embolization by interventional radiologic techniques
      is an effective and widely used modality in the management of uterine leiomyomas.
      Anatomically, uterine arteries can be approached transvaginally with an
      appropriate surgical technique. In this report, we describe a novel, minimally
      invasive vaginal technique that also occluded the uterine arteries successfully.
      CASE: A 45-year-old woman with symptomatic leiomyomas decided to undergo a
      vaginal hysterectomy. During the procedure, Doppler ultrasonography demonstrated
      the cessation of blood flow after dissection and ligation of uterine arteries
      bilaterally without cutting the uterosacral and cardinal ligaments. CONCLUSION:
      Transvaginal ligation of the uterine arteries is possible. If validated by
      further clinical investigation, this minimally invasive gynecologic technique
      could be useful in selected cases of uterine leiomyomas.

PMID- 12815916
TI  - Incomplete bladder emptying after the tension-free vaginal tape procedure,
      necessitating release of the mesh. A report of three cases.
AB  - BACKGROUND: The Tension Free Vaginal Tape (TVT) (Ethicon, Inc., Somerville, New
      Jersey) procedure is a minimally invasive surgical treatment for stress urinary
      incontinence. Urinary retention is a potential complication that may require
      release of the tape. CASES: In three cases, prolonged urinary retention occurred
      after the TVT procedure. Two of the three cases were performed in conjunction
      with anterior repair. All three patients required surgical release of the tape,
      which was located at the urethrovesical junction rather than midurethra. All
      three patients remained stress continent after tape release. One patient
      developed urge incontinence. CONCLUSION: Excessive tension, as well as tape
      migration toward the urethrovesical junction, may be the cause of prolonged
      urinary retention after the TVT procedure. Surgical release of the tape is an
      effective management approach to this complication.

PMID- 12815917
TI  - Comparative genomic hybridization-assisted prenatal diagnosis of a de novo
      inverted duplication of chromosome 10q. A case report.
AB  - BACKGROUND: Comparative genomic hybridization (CGH) can detect chromosomal
      imbalance using genomic DNA extracted from tissue without culture and or
      metaphase spread preparation. It remains a powerful adjunct to conventional
      karyotyping to help solve clinical cytogenetic cases of intricate unbalanced
      aberrations. CASE: A 30-year-old, pregnant woman underwent amniocentesis at 16
      weeks of gestational age. She had received radioiodine treatment for thyroid
      disease 4 years earlier and had delivered a healthy infant after treatment.
      Conventional chromosomal analysis from cultured amniotic fluid cells revealed
      additional material added to the end of the long arm of 1 chromosome 10. With the
      aid of CGH, a cytogenetic diagnosis of 46, XY, inv dup(10)(q26q22) was made.
      CONCLUSION: Though little evidence exists that genetic change on meiosis of
      oocytes could result from radioiodine treatment, attention should still be paid
      to pregnant women who have received it. In the case of doubtful results on
      conventional cytogenetic studies, comparative genomic hybridization could play a
      role.

PMID- 12815919
TI  - [What is a home nursing service?].

PMID- 12815920
TI  - [Assured missions of the home nursing services for the patient, his family and
      other caregivers].

PMID- 12815921
TI  - [Daily experience with home nursing services].

PMID- 12815922
TI  - [Home nursing services, a cross between a care project and a life project].

PMID- 12815923
TI  - [Aging together at home, benefits and limits].

PMID- 12815924
TI  - [Managing Alzheimer's disease. 4/6--nutrition].

PMID- 12815925
TI  - [Should we create units for Alzheimer patients in nursing homes?].

PMID- 12815926
TI  - [When should we think of depression in the elderly patient and how should we
      treat it?].

PMID- 12815927
TI  - [Physical restraint: how to do and above all how not to do?].

PMID- 12815928
TI  - Turmoil vs. crisis.

PMID- 12815929
TI  - Newborn screening in Delaware.
AB  - Newborn screening for metabolic, hematologic, and endocrinologic disorders is a
      well-established public health function. Recent technological advances have made
      screening possible for more disorders. For many of these disorders, there is
      evidence that screening is effective; however, some of these disorders are rare,
      and their response to therapy and their natural history are not completely
      understood. A number of states have instituted "expanded" newborn screening
      utilizing a combination of established and new technologies. Other states,
      including Delaware, have studied the experiences of the states doing expanded
      screening and have decided to proceed with expanded screening as well. Since
      early 2003, Delaware has been screening newborns for about 25 disorders,
      including amino acidopathies, organic acidurias, fatty acid oxidation disorders,
      hemoglobinopathies, and endocrinopathies.

PMID- 12815930
TI  - The social impact of medicine. Chapter 7.

PMID- 12815931
TI  - The medical desert of the American empire.

PMID- 12815932
TI  - Malaria in the third world.

PMID- 12815933
TI  - Oral cancer: the spectrum of diagnosis and treatment.

PMID- 12815934
TI  - Life would be easy ... if it weren't for other people.

PMID- 12815935
TI  - Periodontal disease: a look at historical, current, and future approaches to
      therapy.

PMID- 12815936
TI  - Mission Vietnam: dentistry abroad.

PMID- 12815937
TI  - Utilization of dental care services by Asians and native Hawaiian or other
      Pacific Islanders: United States, 1997-2000.
AB  - OBJECTIVE: This report describes national estimates of dental care service
      utilization and unmet dental care needs due to cost for six Asian ethnic
      subgroups and the native Hawaiian or other Pacific Islander (NHOPI) population.
      METHODS: Combined data from the 1997-2000 National Health Interview Surveys
      (NHISs), conducted by the Centers for Disease Control's National Center for
      Health Statistics, were analyzed to produce estimates for Asians and NHOPIs aged
      2 years and over. Information on dental care service utilization and unmet dental
      care needs due to cost was self-reported by persons aged 18 years and over. For
      children aged 2-17 years, the information was collected from an adult who was
      knowledgeable about the child's health. RESULTS: Approximately 64% of Asian and
      56% NHOPI persons had visited a dentist at least once in the past year.
      Utilization of dental care services, however, varies significantly by ethnic
      subgroup. Asian Indians were most likely to have never had a dental visit and the
      NHOPIs were most likely to experience unmet dental care needs in the past year.
      Among adults, Japanese Americans (68.2%) were most likely and NHOPIs (49.3%) were
      least likely to have had a dental visit in the past year. Underutilization of
      dental care services was most prevalent among Asian adults with poor or near poor
      poverty status, without health insurance coverage, and who had resided in the
      United States for less than 5 years. Among children, NHOPIs (82.0%) were most
      likely and Asian Indians (60.1%) were least likely to have had a dental visit in
      the past year. Underutilization was most prevalent among Asian children who were
      not living with their parents or living with a single parent, who had no
      insurance coverage, who had poor or near poor poverty status, and whose parents
      had less than 12 years of education. CONCLUSIONS: Utilization of dental care
      services and unmet dental care needs due to cost vary among the Asian ethnic
      subgroups and the NHOPI population.

PMID- 12815938
TI  - [Plant resistance genes: molecular and genetic organization, function and
      evolution].
AB  - Remarkable progress is achieved now in comprehension of mechanisms that determine
      functioning of genes responsible for plants' phytopathogenic resistance (genes
      R). Cloning of great number of Monocotyledones and Dicotyledones resistance genes
      show that most of proteins coded by these genes have conserved amino-acid
      motives, which show high homology to amino-acid motives of proteins with well
      designated function. Common structures for most proteins produced by genes R
      include nucleotide-blinding site (NBS), leucine-rich repeat (LRR), site
      containing homology with the cytoplasmic domains of the Drosophila Toll protein
      and the mammalian interleukin-1 receptor (TIR), coiled-coil structure (CC),
      transmembrane domain (TM), and serine/threonine proteinkinase domain (PK). They
      are combined within the basic classes of resistance genes proteins as follows:
      TIR-NBS-LRR, CC-NBS-LLRR, NBS-LRR, PK, TM-CC, LRR-TM, LRR-TM-PK. The domains of
      proteins produced by plant resistance genes cause specific recognition of
      avirulence genes products and activate signaling cascade, which gives rise to
      resistance reaction. Some classes of plant resistance genes probably have the
      same evolutionary origin as the genes that control the innate immunity of ancient
      animals. The evolution of plant R genes proceeds primarily by duplication and
      equal or unequal meiotic recombination. The research on genes R functioning
      besides its theoretical value is a matter of considerable practical interest for
      construction of plant genotypes resistant against harmful organisms. The progress
      in comprehension of mechanisms responsible for specificity of avirulence
      determinants in phytopathogenic organisms recognition makes possible the creation
      of artificial resistance genes.

PMID- 12815939
TI  - [Importance of genetic recombination for the preservation and progress of species
      in the course of evolution].
AB  - The role of genetic recombinations is considered in the context of ecological
      stability of organisms. The ecological stability is taken as a special notion
      distinct from fitness in its original sense as the Maltusian parameter according
      to R. Fisher. The genetic exchange within the species provides the recovery of a
      species specific level of ecological stability that is lowered in particular
      individuals as a result of the accumulation of mutations in microevolutionary
      processes. It is supposed that the accumulation of the mutations that decrease
      organisms' ecological stability leads to the action of truncated selection. This
      type of selection explains the advantage of recombination in the model of A.S.
      Kondrashov (1982). In the evolving species, ecological stability is gradually
      increasing in the process of evolution as a result of hybridization between the
      narrow-specialized races. Genetic recombinations provide a constant DNA
      homogenization within the species and, therefore, the species integrity as an
      elementary structure responsible for the preservation and rise in the level of
      ecological stability of organisms in evolving lineages.

PMID- 12815940
TI  - [The life form concept and the use in the analysis of life cycle evolutionary
      strategies].
AB  - The life form is a generalized morphoecological characteristic of an animal
      giving an idea of the organism as a whole, its position and function and
      functional role in the ecosystem. This characteristic is inherent to a species or
      to a group of congeneric species (for applied goal it is better to use a genus,
      not species) considered in the framework of higher taxon (from family to type).
      The principal contradiction of life form concept is determined by the existence
      of ontogenetic stages and changes of life forms during the whole life of
      individual. It is usually assumed that the concept of life form should be applied
      only to the adult stage, thus ignoring the integral character of the life cycle
      as indivisible unit of selection, evolution and functioning in ecosystem. We
      propose that a morphologically specific ontogenetic of a given species should be
      used as an elementary lowest unit in the classification of life forms. Thus it
      can be considered as integrated internally structured morphoecological unit in
      time and multidimensional space of abiotic and biotic environmental factors. As
      an example we describe the types of reproductive strategies and classification of
      elementary (ontogenetic) life forms in cephalopods. We present characteristics of
      the life cycle of some typical cephalopod species inhabiting different biotopes
      and having different models of locomotion, feeding, reproduction and development.

PMID- 12815941
TI  - How do fish ectoparasites Argulus spp. (Crustacea: Branchiura) match with their
      hosts at the behavioural and ecological scales?
AB  - Features of the Argulus foliaceus and A. coregoni life cycles including spatial
      distribution and hatching patterns of the resting eggs as well as their host
      searching behaviour were analyzed on the basis of field and experimental data
      obtained in lakes and a fish farm in the Central Finland. Published data on
      behaviour and ecology of these parasites were also used. The main point of this
      analysis was an ecological adjustment of the life cycles of parasites to that of
      their fish hosts at different spatial and temporal scales. Due to different
      spatial distribution of overwintering eggs, the newly hatched larvae of A.
      coregoni are more likely to attach to salmonids, which are their main hosts,
      while A. foliaceus to percids and cyprinids. The main peak of argulid hatching
      occurs in late spring-early summer and coincides with the period when most of
      freshwater fishes concentrate close to the shore, either for spawning, or,
      foraging. Nevertheless, despite the general coincidence, the parasite-host
      encounter rate could still be very low. The main peak of hatching is followed by
      a long "tail". We suggest that under fluctuating and uncertain environmental
      conditions characterised by both abiotic stochasticity and poor predictability of
      the hosts, an optimal recruitment strategy is to hedge a bet, with a proportion
      of eggs synchronously hatching and a proportion remaining dormant and hatching at
      much lower rate during an extended period. One of the main behavioural
      adaptations to match with the hosts is all-over-the-day searching activity of
      argulids. The boreal A. coregoni relies primarily on vision, which is most
      effective in transparent waters during long polar days in summer. Vision is also
      important in the behavioural repertoire of the temperate A. foliaceus in the
      light, but olfaction and mechanoreception in the dark provide the highest host
      searching rate. The two generally sympatric species of argulids segregated on the
      finer habitat scale. Partially overlapping on salmonid hosts, they prefer
      ecologically distinct categories of fish, and use different microhabitats for egg
      laying and searching for hosts.

PMID- 12815942
TI  - [Regularities in the variability of species structure of costal littoral kelp:
      the model analysis].
AB  - The model describes species structure of competitive community, inhabiting
      stochastically variable environment.  Species list of this community, rearranged
      accordingly decreasing species abundance, can be described by decreasing
      geometrical series.  According to the model, the value of coefficient of this
      progression q should be q = exp(-1) = 0.368.  The actual data do not contradict
      statistically to this model constant.  Seasonal variability of species structure
      in biotopes is observed.  These biotopes differ one from another by the stability
      and heterogeneity levels of environmental conditions, estimated with the help of
      expert evaluation. Total community biomass shows two seasonal peaks; at winter
      and at spring - summer.  Maximal values of total biomass are observed in the
      biotope with intermediate level of environment stability.  The number of species
      is increased simultaneously with the growth of environmental stability.  The
      level of species abundance equitability grows up too in these conditions.  The
      model of geometric series describes the species structure of the macroalgae
      community quite adequately.  At the same time, the positive correlation between
      sample's species richness and equitability of species structure results in the
      outcome that after all samples averaging the biomass distribution of species is
      approximately more accurately not by geometrical series but by power model. The
      new  statistical method is offered in the application to this work.  It allows
      the expose of statistically significant not monotone essential non-linear
      relations of nonquantitative (order-type) arguments.

PMID- 12815943
TI  - [Mechanisms responsible for the development of periphyton community structure
      during seasonal succession: the role of interspecies competition and plankton
      sedimentation].
AB  - The development of periphyton community structure by exchange of organisms
      between substratum and water column (noninteractive mechanism) and by
      interspecific competition for surface (interactive mechanism) was studied during
      seasonal succession in Akulovsky water supply channel (the Upper Volga basin).
      The influence of exchange was assumed by similarity between the species
      composition of plankton and periphyton. At early stages of succession when the
      diatoms dominated in periphyton the community was formed mainly by phytoplankton
      sedimentation, while the competition for substratum didn't result in decrease of
      species diversity because the poor competitors were partly displaced by new
      colonists from the water column. Later when the green filamentous algae
      abundantly developed in periphyton, their numbers were probably controlled by
      factors not related to exchange of propagules. At the same time, the species
      structure of secondary periphyton cover developing on the thallus of filamentous
      algae depended mainly on the plankton sedimentation. At the last stages of
      seasonal succession when periphyton was represented by colonies of cyanobacteria
      and diatoms closely covering the substratum, the exchange of organisms between
      substratum and water column was not so important as interspecific competition for
      surface. As one could suppose, increase in biomass in this period resulted in the
      decrease of specificity as it was predicted by hypothesis of interactive
      community. In such a way, both mechanisms (interactive and noninteractive ones)
      took part in development of periphyton structure. Their relative influence
      changed in the course of seasonal succession.

PMID- 12815944
TI  - [Na/K pump and intracellular monovalent cations: novel mechanism of excitation
      transcription coupling involved in inhibition of apoptosis].
AB  - The Na/K pump plays a key role in the regulation of the intracellular
      concentrations of monovalent cations and related cell function leading to
      electrogenesis and excitation-contraction coupling. We focus this review on the
      analysis of recent data showing that (i) inhibition of the Na/K pump triggers a
      signaling cascade independently of modulation of the intracellular [Na+]i/[K+]i
      ratio; (ii) elevation of [Na+]i under sustained inhibition of the Na/K pump leads
      to expression of a set of genes by [Ca2+]i-dependent and independent pathways;
      (iii) [Na+]i-sensitive genes are involved in the inhibition of programmed cell
      death (apoptosis) in vascular smooth muscle cells.

PMID- 12815945
TI  - [Alu repeats in the human genome].
AB  - Highly repetitive DNA sequences account for more than 50% of the human genome.
      The L1 and Alu families harbor the most common mammalian long (LINEs) and short
      (SINEs) interspersed elements. Alu elements are each a dimer of similar, but not
      identical, fragments of total size about 300 bp, and originate from the 7SL RNA
      gene. Each element contains a bipartite promoter for RNA polymerase III, a
      poly(A) tract located between the monomers, a 3'-terminal poly(A) tract, and
      numerous CpG islands, and is flanked by short direct repeats. Alu repeats
      comprise more than 10% of the human genome and are capable of retroposition.
      Possibly, these elements played an important part in genome evolution. Insertion
      of an Alu element into a functionally important genome region or other Alu
      dependent alterations of gene functions cause various hereditary disorders and
      are probably associated with carcinogenesis. In total, 14 Alu families differing
      in diagnostic mutations are known. Some of these, which are present in the human
      genome, are polymorphic and relatively recently inserted into new loci. Alu
      copies transposed during ethnic divergence of the human population are useful
      markers for evolutionary genetic studies.

PMID- 12815946
TI  - [The role of region pX in the life cycle of HTLV-I and in carcinogenesis].
AB  - The review considers the molecular biological organization of genome region pX of
      the human T-cell leukemia virus type I (HTLV-I) along with the structure and
      functions of regulatory proteins Tax, Rex, and poorly studied Rof and Tof. Tax
      functions are described, including transcriptional trans-activation, trans
      repression, and effects on apoptosis and the cell cycle. The roles of Tax and Rex
      in controlling gene expression and replication of HTLV-I are discussed.

PMID- 12815947
TI  - [Association of the SOD2 Ala(-9)Val and SOD3 Arg213Gly polymorphisms with
      diabetic polyneuropathy in patients with diabetes mellitus type 1].
AB  - Single-nucleotide polymorphisms of the genes for mitochondrial (SOD2) and
      extracellular (SOD3) superoxide dismutases were tested for association with
      diabetic polyneuropathy (DPN) in diabetes mellitus (DM) type 1. Patients (n =
      180) were divided into two groups with nonoverlapping (polar) phenotypes. Group
      DPN+ included 86 individuals with DPN and DM type 1 record of no more than 5
      years. Group DPN-included 94 patients with DM type 1 record of more than 10 years
      but without clinical signs of DPN. Fisher's exact test revealed significant
      differences in allele and genotype frequencies for the two groups. Higher
      frequencies of SOD2 allele Val and genotype Val/Val and of SOD3 allele Arg and
      genotype Arg/Arg were established for group DPN+. On this evidence, SOD2 and SOD3
      were associated with DPN in DM type 1.

PMID- 12815948
TI  - [Quantitative analysis of repetitive sequences in human genomic DNA and detection
      of an elevated ribosomal repeat copy number in patients with schizophrenia (the
      results of molecular and cytogenetic analysis)].
AB  - A modified version of quantitating repetitive sequences in genomic DNA was
      developed to allow comparisons for numerous individual genomes and simultaneous
      analysis of several sequences in each DNA specimen. The relative genomic content
      of ribosomal repeats (rDNA) was estimated for 75 individuals, including 33
      healthy donors (HD) and 42 schizophrenic patients (SP). The rDNA copy number in
      HD was 427 +/- 18 (mean SE) per diploid nucleus, ranging 250-600. In SP, the rDNA
      copy number was 494 +/- 15 and ranged 280-670, being significantly higher than in
      HD. The two samples did not differ in contents of sequences hybridizing with
      probes directed to a subfraction of human satellite III or to the histone genes.
      Cytogenetic analysis (silver staining of metaphase chromosomes) showed that the
      content of active rRNA genes in nucleolus organizer regions is higher in SP
      compared with HD. The possible causes of the elevated rRNA gene dosage in SP were
      considered. The method employed was proposed for studying the polymorphism for
      genomic content of various repeats in higher organisms, including humans.

PMID- 12815949
TI  - [Molecular genetic analysis of the interleukin 6 and tumor necrosis factor alpha
      gene polymorphisms in multiple myeloma].
AB  - The-174G alpha-->C polymorphism of the interleukin 6 (IL-6) gene promoter and the
      308G alpha-->A polymorphism of the tumor necrosis factor alpha (TNF alpha) gene
      promoter were tested for association with multiple myeloma (MM) varying in
      severity. Of 69 patients, 19 had aggressive MM, 26 had benign MM, and 24 had
      unidentified MM. The control group (N = 102) matched the test group in age and
      sex composition. The two groups did not significantly differ in allele and
      genotype frequencies of the IL-6 and TNF alpha genes. Genotype CC, which
      determines low-level expression of IL-6, occurred at a frequency of 0.35 in
      patients with low-progressing MM and was absent from patients with aggressive MM.
      The TNF alpha gene showed no association with predisposition to MM or clinical
      variant of the disease. On this evidence, the polymorphic variants of the
      cytokine genes were assumed to have no effect on predisposition to MM. As for MM
      progression, genotype CC of the IL-6 gene was associated with milder clinical
      signs in patients from Bashkortostan.

PMID- 12815950
TI  - [Structural and functional analysis of the human ribosomal protein L11 gene].
AB  - The nucleotide sequence was established for the human ribosomal protein L11 gene
      (HRPL11). The gene (4583 bp) proved to consist of six exons and five introns. The
      structure of the HRPL11 promoter was shown to be typical for ribosomal protein
      genes of higher eukaryotes: the promoter lacks TATA or CAAT boxes and has a TATA
      like element (ATAA, -24 ... -27) surrounded by GC-rich regions, the transcription
      start point is within an oligopyrimidine tract, and the 5'-untranslater region is
      short (26 bp). Proteins interacting with the HRPL11 promoter were identified by
      the electrophoretic mobility shift assay with oligonucleotide competitors
      containing known transcription factor-binding sites. The promoter regions were
      compared for the human genes for ribosomal proteins L11, L32, and S26.

PMID- 12815951
TI  - [The informational concept of searching for periodicity in symbol sequences].
AB  - Method of informational decomposition has been developed, allowing one to reveal
      hidden periodicity in any symbol sequences. The informational decomposition is
      calculated without conversion of a symbol sequence into the numerical one, which
      facilitates finding periodicities in a symbol sequence. The method permits
      introducing an analog of the autocorrelation function of a symbol sequence. The
      method developed by us has been applied to reveal hidden periodicities in
      nucleotide and amino acid sequences, as well as in different poetical texts.
      Hidden periodicity has been detected in various genes, testifying to their
      quantum structure. The functional and structural role of hidden periodicity is
      discussed.

PMID- 12815952
TI  - [The role of the serotonin system in the stress response of various cells].
AB  - The recombinant mouse brain serotonin receptor (5HT1c) was used to study the
      response of plant cells and oocytes to a stress signal activated by the serotonin
      serotonin receptor interaction and associated Ca2+ flow. Based on plant
      expression vectors, recombinant constructs were obtained to direct production of
      5HT1c fused with the green fluorescent protein in plant cells. The mRNAs for
      hybrid proteins were synthesized in an in vitro transcription system. The
      expression and function of the hybrid protein and the function of the associated
      ion channels were electrophysiologically studied in Xenopus laevis oocytes
      injected with the hybrid mRNA. The hybrid protein was functional and changed the
      operation of the Ca2+ channel in oocytes. To study the expression of the hybrid
      constructs in plant cells, the in vitro transcription product was inoculated in
      tobacco leaves, which then fluoresced.

PMID- 12815954
TI  - [Cervical carcinoma progression-associated genetic alterations on chromosome 6].
AB  - To identify the loci associated with progression of cervical carcinoma,
      chromosome 6 regions were tested for loss of heterozygosity. Detailed analysis
      with 28 microsatellite markers revealed a high frequency of allelic deletions for
      several loci of the short (6p25, 6p22, 6p21.3) and long (6q14, 6q16-21, 6q23-24,
      6q25, 6q27) arms of chromosome 6. Examination of 37 microdissected carcinoma and
      22 cervical dysplasia specimens revealed allelic deletions from the HLA class I
      III genes (6p22-21.3) and subtelomeric locus 6p25 were found in more than 40%
      dysplasia specimens. With multiple microdissection of cryosections, genetic
      heterogeneity of squamous cervical carcinoma was analyzed, and clonal and
      subclonal allelic deletions from chromosome 6 were identified. Half of the tumors
      had clonal allelic deletion of D6S273 (6p21.3), which is in a Ly6G6D (MEGT1)
      intron in the HLA class III gene locus. The frequency of allelic deletions from
      the chromosome 6 long arm was no more than 20% in dysplasias. Allelic deletions
      from two loci, 6q14 and 6q16-21, were for the first time associated with invasion
      and metastasis in cervical carcinoma.

PMID- 12815953
TI  - [The protective role of p53 in Ras-induced transformation of REF52 cells].
AB  - A study was made of the effect of activated oncogene N-RAS on the function of
      tumor suppressor p53 and the proliferating ability of rat embryo fibroblasts
      REF52. The proliferation rate and the portion of S-phase cells increased in the
      first three days of N-RAS expression. After 5-7 days, the p53 function was
      enhanced, as manifest in increased p53 lifespan and nuclear content and induced
      transcription of p53-responsive genes. In particular, Cdk2 p21WAF1/CIP1, an
      inhibitor of cyclin-dependent kinase 2, was produced to a higher level and
      arrested the cell cycle in G1. Cells with abrogated or dramatically inhibited N
      RAS expression were generated at this stage. Having a selective advantage, these
      cells gradually displaced N-RAS-expressing cells arrested in G1, so that one
      month after oncogene induction the culture mostly consisted of morphologically
      normal, actively proliferating Res-negative cells. Neither cell cycle arrest nor
      reversion to the normal phenotype were observed in N-RAS expressing cells devoid
      of the p53 function. Thus, p53 prevented stable N-RAS-induced transformation of
      REF52 cells, arresting the cell cycle and expediting revertant selection.

PMID- 12815955
TI  - [Effect of catalase on the expression of NO-dependent genes in primary
      chondrocytes].

PMID- 12815956
TI  - [Highly conserved region 1816-1831 of the 18S ribosomal RNA is close to the first
      nucleotide of the A-site codon in elongation and termination of translation].
AB  - Two mRNA analogs, pUUCUAAA (with stop codon UAA) and pUUCUCAA (with Ser codon
      UCA) containing a perfluoroarylazido group at U4, were used to study the position
      relative to the 18S rRNA for the first nucleotide of the codon located in the A
      site of the human 80S ribosome. To place UAA or UCA in the A site, UCC
      recognizing tRNAPhe was bound in the P site. With each analog, crosslinking was
      detected for highly conserved fragment 1816-1831, which contains invariant
      dinucleotide A1823/A1824 and is in helix 44 at the 3' end of the 18S rRNA. Since
      18S rRNA modification did not depend on whether the U4 photoreactive group was in
      the sense or stop codon, it was assumed that polypeptide chain release factor 1
      directly recognizes the trinucleotide of a stop codon located in the A site.

PMID- 12815957
TI  - [Minor secondary-structure variation in the 5'-untranslated region of the beta
      globin mRNA changes the concentration requirements for eIF2].
AB  - Nucleotide sequence changes increasing the number of paired bases without
      producing stable secondary structure elements in the 5'-untranslated region (5'
      UTR) of the beta-globin mRNA had a slight effect on its translation in rabbit
      reticulocyte lysate at its low concentration and dramatically decreased
      translation efficiency at a high concentration. The removal of paired regions
      restored translation. Addition of purified eIF2 to the lysate resulted in equal
      translation efficiencies of templates differing in structure of 5'-UTR. A similar
      effect was observed for p50, a major mRNP protein. Other mRNA-binding initiation
      factors, eIF4F and eIF3B, had no effect on the dependence of translation
      efficiency on mRNA concentration. Analysis of the assembly of the 48S initiation
      complex from its purified components showed that less eIF2 is required for
      translation initiation on the beta-globin mRNA than on its derivative containing
      minor secondary structure elements in 5'-UTR. According to a model proposed, eIF2
      not only delivers Met-tRNA, but it also stabilizes the complex of the 40S
      ribosome subunit with 5'-UTR, which is of particular importance for translation
      initiation on templates with structured 5'-UTR.

PMID- 12815958
TI  - [Distribution of the Xvent-2 mRNA between informosomes and polysomes in early
      frog development].
AB  - Translational expression regulation was studied for Xvent-2 coding for a
      transcription factor involved in dorsoventral differentiation of amphibian
      embryos. The Xvent-2 mRNA was detected predominantly in informosomes at all
      developmental stages examined, and only its minor fraction was associated with
      polysomes. Expression of Xvent-2 was assumed to be regulated at the translational
      level, with Xvent-2 produced immediately before polypotent cells enter a certain
      differentiation pathway.

PMID- 12815959
TI  - [Some structural aspects of the peptidyltransferase reaction].

PMID- 12815960
TI  - [A comparative analysis of interhelical polar interactions of various alpha-helix
      packings in proteins].
AB  - One hundred twenty globular proteins and forty five "leucine zippers"
      representing all types of packing of long alpha-helices were studied in terms of
      revealing and comparing their interhelical hydrogen and salt bonds. Many previous
      studies of "leucine zippers" and their analogs showed that interhelical
      interactions between polar groups could impart specificity to packing of an alpha
      helix. The current comparison demonstrated that basically, globular proteins and
      "leucine zippers" had similar interhelical polar interactions with presumably a
      similar structural role. However, depending on packing of alpha-helices, the
      networks of interhelical polar bonds were shown to be distinct and determined
      both by physicochemical properties of involved amino acid residues and by the
      relative positions of hydrophobic and hydrophilic residues on the surface of
      alpha-helices. The revealed distinction is probably crucial for selecting the
      unique packing of an alpha-helix.

PMID- 12815961
TI  - [The role of structural elements in dimerization of RNA fragments in avian
      retroviruses].
AB  - The slipped loop structure, earlier identified as an unusual DNA structure, was
      found to be a possible element of the RNA folding. In order to experimentally
      test this suggestion, model oligoribonucleotides capable of forming the SLS were
      synthesized. Treatment of the oligoribonucleotides with nuclease S1 and RNases
      specific for single- and double-stranded RNA demonstrated the steric possibility
      of SLS formation. To determine the possible functional role of SLS-RNA, various
      naturally occurring RNAs were screened in silico. Among the most interesting
      findings were dimerization initiation sites of avian retroviral genomic RNAs.
      Analysis of RNA from 31 viruses showed that formation of the intermolecular SLS
      during RNA dimerization is theoretically possible, competing with the formation
      of an alternative hairpin structure. Identification of the secondary structure of
      selected RNA dimers employing nuclease digestion techniques as well as covariance
      analysis of the retroviral RNA dimerization initiation site sequences were used
      to show that the alternative conformation (loop-loop interaction of two hairpins)
      is the most preferred. Alternative structures and conformational transitions in
      RNA dimerization mechanisms in avian retroviruses are discussed.

PMID- 12815962
TI  - [DNA duplexes containing 2'-deoxy-2'-iodoacetamidouridine as reagents for
      affinity modification of proteins].
AB  - DNA duplexes containing the iodoacetamido group at position 2' of the ribose
      moiety were proposed for affinity modification of Cys in DNA-binding proteins.
      Reactive DNA derivatives were obtained with iodoacetic anhydride and synthetic
      oligodeoxyribonucleotides containing 2'-amino-2'-deoxyuridine in place of thymine
      at various positions. The derivatives were tested for reaction with amino acids
      and peptides and shown to specifically interact with Cys-containing proteins. The
      possibility of using the modified DNA duplexes to probe the protein SH group
      close to the DNA sugar-phosphate backbone in DNA-protein complexes was
      demonstrated with the example of subunit p50 of human transcription factor NF
      kappa B.

PMID- 12815963
TI  - [Experimental molecular design of recombinant vaccines].
AB  - A method was elaborated to construct combined artificial immunogens mimicking
      virus particles. The gist was exposing protein antigenic determinants of one
      virus on the particle surface and delivering plasmids with genes for antigenic
      proteins of another virus to specialized immune cells. Such immunogens were
      constructed and shown to induce biosynthesis of specific antibodies against HIV-1
      and the tick-borne encephalitis virus. The level and duration of the humoral and
      cell responses were assayed.

PMID- 12815964
TI  - [The effect of losing glycosylation sites near the receptor-binding region on the
      receptor phenotype of the human influenza virus H1N1].
AB  - The receptor properties of influenza virus (IF) isolates/SSSR/90/77 are studied.
      The isolates are peculiar for losing glycosylation sites (GS) at the Asn131
      receptor-binding region (GS131) after passaging in mice and at the Asn158 region
      (GS158) after cultivation in the presence of mouse serum. The loss of each
      carbohydrate residue increases the influenza virus affinity for carbohydrate
      chains with the terminal group Neu5Ac alpha 2-6Gal and reduces its affinity for
      Neu5Ac alpha 2-3Gal receptors. The effect is more pronounced in the GS158
      depleted virus. Upon substitution of asparagine by aspartic acid, the
      electrostatic component of virus binding to the receptor is altered because of
      the increased negative charge on hemagglutinin. The virus receptor phenotype
      changes depending on the cultivation conditions. The isolate adapted to mice has
      higher affinity to mouse lung cell receptors, while the virus propagated in chick
      embryos in the presence of inhibitors has higher affinity to allantoic membrane
      cells.

PMID- 12815965
TI  - [Immunogenetic properties of peptides mimicking a human immunodeficiency virus
      gp41 (HIV-1) epitope recognized by virus-neutralizing antibody 2F5].
AB  - Phage display was used to obtain peptides mimicking a HIV-1 gp41 conserved
      epitope recognized by virus-neutralizing monoclonal antibodies (MCA) 2F5. Rabbits
      and mice were immunized with the peptides exposed on the surface of filamentous
      bacteriophages. Antibodies to gp41 were detected in the sera of immunized
      animals. The virus-neutralizing activity of the sera was examined.

PMID- 12815966
TI  - [Effect of temperature, pH, and organic phosphates on hemoglobins in fishes].

PMID- 12815967
TI  - [Insulin-like growth factor-1 receptor in tissues of the mollusk Anodonta cygnea
      ].

PMID- 12815968
TI  - [Role of insulin and insulin-like growth factor-1 (IGF-1) on glycogen synthase
      activity in the skeletal muscles of the lamprey Lampetra fluviatilis].

PMID- 12815969
TI  - [Effect of adrenaline on amylolytic activity of intestinal mucose, glycemia
      level, glycogen concentration in tissues of carp Carassius auratus and carp
      Carassius carassius].

PMID- 12815971
TI  - [Acetylcholinesterase activity of the sensomotor cortex in early ontogenesis in
      rats after prenatal hypoxia].

PMID- 12815970
TI  - [Different sensitivity of synaptic inputs of motor neurons to excitatory amino
      acid antagonists in the frog Rana ridibunda].

PMID- 12815972
TI  - [Secondary rhythms of the heart activity during ontogenesis in rats].

PMID- 12815973
TI  - [Reorganization of content in the striatum neurons related to behavior in the
      monkey Macaca nemestrina].

PMID- 12815975
TI  - [NO-synthase in the central nervous system of fresh water bivalve mollusk
      Nodularia vladivostokensis in normal conditions and during hypoxia ].

PMID- 12815974
TI  - [Sex differences in the effects of prenatal stress on specific two-phases
      behavioral response in nociception formalin test in adult rats].

PMID- 12815976
TI  - [Electron microscopy study of the frontal neurohypophysis of the sterlet
      Acipenser ruthenus].

PMID- 12815977
TI  - [Neuronal organization of the stellate ganglion in mammals during postnatal
      ontogenesis].

PMID- 12815979
TI  - [Is it beneficial to operate a localized prostate cancer?].

PMID- 12815978
TI  - [When should the medication for dementia be stopped?].

PMID- 12815980
TI  - [Tacrolimus and pimecrolimus ointments in the treatment of atopic eczema].

PMID- 12815981
TI  - [Reactive arthritis].

PMID- 12815982
TI  - [Future visions of lymphoma diagnosis].

PMID- 12815983
TI  - [Brain imaging in eating disorders and obesity reseach].

PMID- 12815984
TI  - [How are you doing, Current Treatment Praxis?].

PMID- 12815985
TI  - [Treatment of atrial fibrillation with the means of linear ablation during
      cardiac surgery].

PMID- 12815986
TI  - [Severe arterial thromboses associated with thrombophilia].

PMID- 12815987
TI  - [Cholesterol memories].

PMID- 12815988
TI  - [Persistent sinusitis in a young soldier].

PMID- 12815989
TI  - [Studies on the structure of double-helix DNA in the last half century].

PMID- 12815990
TI  - [Thoughts on double-helix DNA].

PMID- 12815991
TI  - [Influence of Dr. Chargaff in the study of the structure of double helix DNA and
      what I learned from it].

PMID- 12815992
TI  - [Studies on the structure of double helix DNA in the last half century:
      Attraction of DNA].

PMID- 12815993
TI  - [Studies on the structure of double-helix DNA in the last half century: DNA
      tail].

PMID- 12815994
TI  - [My study of DNA in the last 40 years].

PMID- 12815995
TI  - [Studies of DNA, genome, and the Human Genome Project].

PMID- 12815996
TI  - [Why are genomes DNA?].

PMID- 12815997
TI  - [Studies on the structure of double-helix DNA in the last half century: Genomic
      studies of Bacillus subtilis and other bacteria].

PMID- 12815998
TI  - [Studies on the structure of double-helix DNA in the last half century: My study
      of DNA].

PMID- 12815999
TI  - [Studies on the structure of double-helix DNA in the last half century: Terminal
      structure of DNA].

PMID- 12816000
TI  - [Studies on the structure of double-helix DNA in the last half century: DNA
      replication priming and cytokine networks].

PMID- 12816001
TI  - [Studies on the structure of double-helix DNA in the last half century:
      Legislation for molecular biological research utilizing radioisotopes in Japan].

PMID- 12816002
TI  - [Studies on the structure of double helix DNA in the last half century: Changes
      in the nature of scientific research].

PMID- 12816003
TI  - [Studies on the structure of double-helix DNA in the last half century in Japan].

PMID- 12816004
TI  - [Role of homologous DNA recombination in regulation of molecular evolution].

PMID- 12816005
TI  - [A historical view of the double helix: its discovery, proof and prospects].

PMID- 12816006
TI  - [Days devoted to elucidating the mechanism of discontinuous DNA replication].

PMID- 12816008
TI  - [Identification and function of protein glutamine (N5) methyl transferase].

PMID- 12816007
TI  - [SOS responses to the mechanism of Holliday junction resolution by RuvABC
      proteins].

PMID- 12816009
TI  - [New progress in research on peptidyl built-in cofactors].

PMID- 12816010
TI  - [Identification of genes by mouse genome and transcriptome analysis].

PMID- 12816011
TI  - [Integrated database for mutations in disease genes: MutationView/KMDB].

PMID- 12816012
TI  - Prostate cancer--testing, incidence, surgery and mortality.
AB  - OBJECTIVES: This article examines recent use of the prostate-specific antigen
      (PSA) test and presents trends in prostate cancer incidence, surgery and
      mortality. DATA SOURCES: Data are from the 2000/01 Canadian Community Health
      Survey, the National Cancer Incidence Reporting System and the Canadian Cancer
      Registry, the Hospital Morbidity Database, and the Canadian Mortality Database.
      ANALYTICAL TECHNIQUES: Descriptive data on PSA testing among men aged 40 or older
      were produced. Age-standardized prostate cancer incidence, surgery and mortality
      rates were calculated. Significant changes in linear trends were detected with
      joinpoint analysis. Provincial differences in incidence and mortality rates were
      tested using a one-way analysis of variance (ANOVA). MAIN RESULTS: In 2000/01,
      43% of Canadian men aged 40 or older reported having had a PSA test. Prostate
      cancer incidence rates rose in the early 1990s, but have since fallen. Prostate
      cancer mortality rates have decreased among men aged 60 or older, but show little
      change among younger men. While interprovincial differences in rates of PSA
      testing were significant, differences in incidence and mortality rates were not
      pronounced.

PMID- 12816013
TI  - Social support and mortality in seniors.
AB  - OBJECTIVES: This article investigates the effect of social support on mortality
      among Canadian seniors. DATA SOURCE: The analysis is based on longitudinal
      household data from the National Population Health Survey (NPHS) for 2,422 people
      aged 65 or older in 1994/95. Vital status and date of death were established
      using data collected in 2000/01. ANALYTICAL TECHNIQUES: Multivariate proportional
      hazards models were used to study associations between four indicators of social
      support (marital status; social contacts; participation in organizations; and
      perceived emotional support) in 1994/95 and death by 2000/01. Separate analyses
      were performed for men and women. MAIN RESULTS: When the influence of age, socio
      economic status, stress, health-related behaviours and physical/mental health
      status was taken into account, no association between social support and
      mortality emerged for women, but such a relationship was evident for men. Married
      men had a 40% lower hazard of death, compared with their non-married
      counterparts. Participation in organizations also conferred a reduced likelihood
      of dying for men.

PMID- 12816015
TI  - NQF endorses 30 universal health care safe practices.

PMID- 12816014
TI  - Tracking diabetes: prevalence, incidence and risk factors.
AB  - OBJECTIVES: This article examines the prevalence and incidence of diabetes among
      Canadians aged 18 or older and risk factors associated with developing the
      condition. DATA SOURCES: The data are from the 1994/95, 1996/97, 1998/99 and
      2000/01 National Population Health Survey and the 2000/01 Canadian Community
      Health Survey, both conducted by Statistics Canada. ANALYTICAL TECHNIQUES:
      Descriptive statistics on the prevalence and incidence of self-reported diabetes
      were computed. Multiple logistic regression was used to identify predictors of
      incident diabetes. Age-adjusted rates were used to compare diabetic and non
      diabetic respondents on a variety of health measures. MAIN RESULTS: In 2000/01,
      4.5% of Canadians aged 18 or older, an estimated 1.1 million, reported having
      diabetes. The incidence from 1994/95 to 2000/01 was 4.9 new cases per 1,000
      person-years at risk. When the possible confounding effects of a number of
      factors were taken into account, advancing age, family history, sedentary leisure
      time and excess weight were associated with developing diabetes.

PMID- 12816016
TI  - Health systems struggling with HIPAA privacy rules.

PMID- 12816017
TI  - Firms take another step to stop counterfeits.

PMID- 12816018
TI  - New drugs and dosage forms.

PMID- 12816019
TI  - Implementing a pharmacist-provided discharge counseling service.

PMID- 12816020
TI  - Policosanol.

PMID- 12816021
TI  - Generic injectable drugs: from idea to market.

PMID- 12816022
TI  - Improving primary care in rural Alabama with a pharmacy initiative.
AB  - The effect of pharmaceutical care on the prevention, detection, and resolution of
      medication-related problems in high-risk patients in a rural community was
      studied. Adult patients who received care at clinics in a medically underserved
      area of Alabama and who were identified as being at high risk of medication
      related adverse events were randomly assigned to a control group or an
      intervention group. The control group received standard medical care, and the
      intervention group received pharmaceutical care, including a medical record
      review, a medication history review, pharmacotherapeutic evaluation, and patient
      medication education and monitoring over a one-year period. A total of 69
      patients completed the study (33 in the intervention group and 36 in the control
      group). The percentage of patients responding to hypertension, diabetes,
      dyslipidemia, and anticoagulation therapy increased significantly in the
      intervention group and declined in the control group. Ratings for inappropriate
      prescribing improved in all 10 domains evaluated in the intervention group but
      worsened in 5 domains in the control group. There were no significant differences
      between the groups at 12 months in health-related quality of life or medication
      misadventures. Medication compliance scores improved in the intervention group
      but not in the control group. Medication knowledge increased in the intervention
      group and decreased in the control group. Pharmaceutical care in a rural,
      community-based setting appeared to reduce inappropriate prescribing, enhance
      disease management, and improve medication compliance and knowledge without
      adversely affecting health-related quality of life.

PMID- 12816023
TI  - Accuracy of home blood glucose monitors using forearm blood samples: FreeStyle
      versus One Touch Ultra.
AB  - The accuracy of two home blood glucose monitors using forearm blood samples was
      studied. Blood samples were obtained from adults by venipuncture and analyzed for
      glucose concentration. Within five minutes after venipuncture, peripheral blood
      glucose measurements were taken in duplicate with the FreeStyle and One Touch
      Ultra monitors by using the same forearm as used for venipuncture. Accuracy was
      assessed by comparing the results for each first peripheral stick obtained by
      each monitor with the laboratory reference value. Monitor precision was evaluated
      by evaluating the mean difference in glucose values between the first and second
      peripheral sticks. Blood samples were obtained from 250 subjects, 170 (68%) of
      whom had diabetes mellitus. A total of 98.8% and 98.4% of the blood glucose
      readings obtained with FreeStyle and One Touch Ultra, respectively, were
      clinically acceptable, and 65.2% and 59.2% of the measurements, respectively,
      were within 10% of the laboratory reference values. The average difference
      between the first and second glucose measurements was 9.7 mg/dL for FreeStyle and
      5.2 mg/dL for One Touch Ultra. One peripheral stick was needed to obtain an
      adequate blood sample in 95.6% of subjects using FreeStyle, compared with 83.2%
      of subjects using One Touch Ultra. Forearm blood glucose measurements obtained
      with the FreeStyle and One Touch Ultra devices were similar to laboratory
      reference values obtained by venipuncture.

PMID- 12816024
TI  - Role of pharmacy experience and argument types in forming beliefs about
      pharmacist trustworthiness.
AB  - The role of pharmacy experience and argument types in forming beliefs about
      pharmacist trustworthiness was studied. Study participants were recruited from
      three primary care clinics. They were provided a pharmacy scenario that contained
      information that could be used to form causal and authoritative arguments. The
      participants rated the trustworthiness of the pharmacist in the scenario on a 10
      point, Likert-type scale and provided the arguments used to form the
      trustworthiness belief. Information that contradicted the pharmacist's
      trustworthiness was then presented in the form of an addendum, and the
      participants reassessed the pharmacist's trustworthiness. Participants rated the
      pharmacist using a Likert-type scale. Responses were coded and analyzed. Initial
      trustworthiness and post-trustworthiness scores were calculated. Participants'
      pharmacy experience score was also determined. Reliability and principal
      components analyses were conducted to determine the quality of the
      trustworthiness and pharmacy experience scores. A total of 130 patients
      participated in the study. There was a positive correlation between pharmacy
      experience and the number of causal arguments that subjects used to form their
      beliefs about pharmacist trustworthiness (r = 0.223, p = 0.012). Results of t
      tests revealed that belief strength was similar among subjects using more causal
      than authoritative arguments to form beliefs and in those using fewer causal
      arguments (t = 1.35, p = 0.179), but belief tenacity differed significantly
      between the groups (t = -2.303, p = 0.023). The role of external sources in
      influencing the formation of beliefs about trustworthiness of a pharmacist may be
      limited as a patient gains pharmacy experience, as experience is based on causal
      associations. Moreover, causal arguments are correlated with belief tenacity.

PMID- 12816025
TI  - Prescriber and pharmacist responses to intervention letters for Connecticut
      Medicaid beneficiaries with asthma.

PMID- 12816026
TI  - Insulin in the treatment of type 2 diabetes mellitus.

PMID- 12816027
TI  - 2002 ASHP Leadership Conference on Pharmacy Practice Management executive
      summary. Leadership in a challenging environment: navigating the forces of
      change.

PMID- 12816028
TI  - Effect of pharmacist emigration on pharmaceutical services in southern Africa.

PMID- 12816029
TI  - [Causality and statistical association (2) Mechanical determinism and stochastic
      model].

PMID- 12816030
TI  - [Paul Broca: the protohistory of neurosurgery].

PMID- 12816031
TI  - [Severe acute asthma].
AB  - A severe acute asthma attack is defined by the presence of clinical signs of
      severity and/or a value of peak expiratory flow (PEF) < 30% predicted. The
      treatment is based mainly on inhaled beta 2 agonists and systemic
      corticosteroids. Nebulization is the route of administration of choice, because
      of its simplicity, its efficacy and its tolerability. Anticholinergics are
      indicated in association with nebulised beta 2 agonists. Response to treatment
      must be evaluated within an hour, permitting the early detection of "responders"
      or "non-responders" to the initial treatment. The great majority of deaths from
      acute asthma are avoidable, underlining the importance of preventive measures.
      Prevention is based on the control of the asthma by personalized ongoing
      treatment based on long-term inhaled corticosteroids and the use of oral
      corticosteroids in the treatment of exacerbations. However, a severe acute asthma
      attack can appear at any stage of severity of asthma, including controlled
      asthma, justifying the utilisation of action plans to treat exacerbations.

PMID- 12816032
TI  - [Acute respiratory distress syndrome].
AB  - Acute respiratory distress syndrome (ARDS) is a non cardiogenic pulmonary edema
      that results from several pulmonary or extrapulmonary insults. ARDS respiratory
      manifestations, in fact, represent the expression of a complex and diffuse
      inflammatory process involving other organs. Mechanical ventilation is considered
      to be a cornerstone of treatment. Alterations in respiratory mechanic (decrease
      in compliance) mainly due to the reduction in non-atelectasis lung volume, are
      responsible for the high airway pressure observed during mechanical ventilation.
      Since mechanical ventilation, itself, could promote lung injury, a ventilatory
      strategy combining both, low volumes to limit distension and positive end
      expiratory pressure to recruit atelectasis may be beneficial. This hypothesis has
      been recently confirmed in a study involving more than 800 patients,
      demonstrating that a simple ventilatory strategy based on recent physiological
      knowledge may affect ARDS outcome.

PMID- 12816033
TI  - [Cardiogenic pulmonary edema in the elderly].
AB  - Heart failure of elderly patients is a frequent disease. It is responsible for
      recurrent hospitalizations and an important mortality rate. The diagnosis of
      cardiogenic pulmonary edema may be difficult in elderly patients. In more than
      50% of cases, echocardiography shows evidence of diastolic heart failure. Medical
      treatment mainly relies on high doses nitrates. Non invasive ventilation
      decreases cardiogenic pulmonary edema morbidity and early mortality.

PMID- 12816034
TI  - [Pneumothorax].
AB  - Spontaneous idiopathic pneumothorax occurs frequently in young tall subjects with
      smoking habits, and is usually of good prognosis. Secondary pneumothorax is a
      life-threatening complication of an underlying lung disease, such as acute
      pneumonia. Pneumocystis carinii pneumonitis or chronic obstructive pulmonary
      disease. Short-term therapeutic options oppose non-traumatic needle aspiration,
      with a success rate of more than 50%, versus thoracic drainage, with a recurrence
      rate exceeding 35%. The existing literature also indicates that video-assisted
      surgery leads to a much better long-term prognosis than the standard drainage
      procedure, with a long-term recurrence rate of less than 2%, for equivalent
      hospital stays and complication rates. The widely accepted recommendation that
      surgery should be proposed only at the first or second pneumothorax recurrence
      may be challenged in the next decade.

PMID- 12816035
TI  - [Thoracic trauma].
AB  - Approximately 30% of trauma cases include significant chest trauma as a
      component. The vast majority of chest trauma is related to motor vehicle
      accidents. A key of management of patients with blunt thoracic trauma is a high
      index of suspicion for thoracic injury, in particular aortic injury. This is
      based on history, including knowledge of the type and force of injury, and
      clinical examination. The majority of such injuries may be diagnosed with
      relatively simple tests such as chest radiographs. Transesophageal
      echocardiography and CT scan are becoming the corner-stone of evaluation of
      severe chest trauma patients.

PMID- 12816036
TI  - [Hemoptysis].
AB  - Hemoptysis is a common respiratory symptom that always requires investigation.
      Its severity varies from bloodstained sputum to life-threatening hemoptysis.
      Blood originates most often from bronchial circulation. The most common causes of
      hemoptysis are tuberculosis, lung carcinoma, bronchiectasis but idiopathic forms
      are frequent. The diagnostic investigation is based mainly on history, chest
      radiograph, fibroscopy and CT scan of the thorax. The goal is to determine the
      cause as well as the site of bleeding. The management of life-threatening
      hemoptysis is mainly based on either surgical approach or bronchial artery
      embolization. The majority of centers favor this latter approach.

PMID- 12816037
TI  - [Non-invasive ventilation for acute respiratory insufficiency].
AB  - Non-invasive ventilation provides ventilatory support to patients admitted for
      acute respiratory failure, without the need for endotracheal intubation or
      tracheostomy. Most of the times, a full face mask covering both the nose and the
      mouth is used. This technique is mainly delivered in intensive care departments,
      but tends to spread to emergency departments, respiratory wards or pre-hospital
      settings. Its aim is to prevent patient's worsening and need for endotracheal
      intubation. It is particularly successful for patients suffering from acute
      exacerbation of chronic obstructive pulmonary disease and in asphyxic forms of
      cardiogenic pulmonary oedema. In these indications, non-invasive ventilation
      reduces the need for intubation, improves hospital length of stay and outcome.
      Other forms of acute hypoxemic respiratory failure with isolated lung failure can
      also benefit from this technique.

PMID- 12816038
TI  - [Acute laryngeal dyspnea].
AB  - Laryngeal dyspnea is a life-threatening emergency situation. The diagnosis is
      clinical and made from the association of: inspiratory bradypnea, intercostal and
      sus-sternal inspiratory depression, with or without stridor. The aetiologies are
      most often laryngeal tumours or inflammatory oedema; incidence of epiglottitis
      has decreased due to vaccine against Haemophilus influenzae. Airway obstruction
      due to foreign body includes acute laryngeal dyspnea and reflex paroxysmal
      coughing without fever. Management of a laryngeal dyspnea depends on the
      aetiology and the severity of clinical symptoms. Medical treatment associates
      racemic epinephrine aerosol, steroids, and oxygenation. In the presence of severe
      dyspnea, intubation after anaesthetising the patient and positive pressure
      ventilation is required.

PMID- 12816039
TI  - [Medical prescriptions: press review].

PMID- 12816040
TI  - [Type I diabetes in adults and children].

PMID- 12816041
TI  - [Sexually transmitted diseases. Gonorrhea, chlamydiosis, syphilis].

PMID- 12816042
TI  - [Andropause].

PMID- 12816043
TI  - [Ectopic pregnancy].

PMID- 12816044
TI  - [Diplopia. Diagnostic management].

PMID- 12816045
TI  - [Evaluation of the severity and early complications of cranio-facial trauma].

PMID- 12816046
TI  - [Stem cells].

PMID- 12816047
TI  - [Transplantation of stem/progenitor cells of human brain into the brain of adult
      rats].
AB  - We studied the development of stem/progenitor cells of the human brain
      transplanted in the adult rat brain after reproduction in an in vitro tissue
      culture. It was preliminarily shown by the immunological methods that the stem
      cells grown in a medium with growth factors formed neurospheres, which were
      heterogenous and contained both stem and progenitor cells of the human brain. The
      cells were implanted in the hippocampus, striatum, or lateral ventricle of the
      rat brain as a suspension or aggregates (neurospheres) and their behavior and
      differentiation were studies within 10, 20, and 30 days using the morphological
      and immunochemical methods. The cultured cells of the human brain continued their
      development in the rat brain, migrated, and formed neurons and astrocytes. The
      white mater fibers, lateral ventricle wall, and perivascular spaces served as the
      main pathways of migration. The neuronal differentiation was shown by staining
      with antibodies to beta-tubulin III, neurofilaments-70, and calbindin. Some
      growing nerve cells had long processes with growth cones. At the same time, some
      transplanted cells retained the undifferentiated state within one month after the
      implantation, as shown by the vimentin expression.

PMID- 12816048
TI  - [Expression of regulatory genes Oct-4, Pax-6, Prox-1, Ptx-2 at the initial stages
      of differentiation of embryonic stem cells in vitro].
AB  - The expression of regulatory genes of the POU, Pax, Prox, and Ptx gene families
      was studied at the initial stages of differentiation of murine embryonic stem
      cells of R1 line. mRNAs were isolated from undifferentiated embryonic stem cells
      and embryoid bodies formed at the early stages of in vitro differentiation and
      cDNA sequences were synthesized for comparative PCR analysis of the expression of
      studied genes. The levels of expression of the gene Oct-4 involved in maintenance
      of the pluripotent status of embryonic stem cells proved to be practically
      indistinguishable in undifferentiated cells and embryoid bodies, while the
      expression of Pax-6 markedly increased in the latter. The levels and patterns of
      expression of the homeobox transcription factors Prox-1 and Ptx-2 were compared
      on this cell model for the first time. A probable role of these genes in
      differentiation of the murine embryonic stem cells is discussed.

PMID- 12816049
TI  - [Telomerization as a method of obtaining immortal human cells preserving normal
      properties].
AB  - Most human somatic cells have no telomerase activity. This leads to terminal
      underreplication of chromosomes and, hence, proliferative ageing of cells. We
      studied the consequences of introduction of the gene of the catalytic component
      of human telomerase hTERT in the normal fibroblasts of adult human skin. The
      expression of this gene led to the appearance of telomerase activity in the
      fibroblasts, elongation of telomeres (to the size characteristic of the embryonic
      cells), and immortalization. The cells retained their normal karyotype. The
      activity of ribosomal genes remained unchanged: the degree of their methylation,
      abundance, and transcriptional activity (two clones were studied). The cells did
      not undergo significant changes after transition over the Hayflick's limit,
      retained the constant rate of proliferation (one of the clones was followed to
      the level of 200 duplications of the population), and resembled, in appearance,
      young diploid human fibroblasts. The initial cells and cells transfected by an
      empty vector could pass through no more than 68 duplications, their proliferation
      slowed down and they acquired the morphology characteristic for the ageing cells.
      The telomerized cells retained the normal capacity of entering the proliferative
      rest as a result of serum starvation. Telomerization did not eliminate the
      contact inhibition of proliferation but led to an increased saturating density of
      cells, which reached the levels characteristic for the early embryonic cells. The
      long-term suppression of the telomerase function by azidothymidine led to a
      shortening of telomeres and significantly slowed down cell proliferation. The
      cells that did not divided for a long time were enlarged, preserved their
      viability, and resembled, in appearance, the ageing cells. In the test on
      heterokaryons (index of telomerase activity on the chromosomes inside the cell),
      the telomerized cells behaved as other immortal cells. All these data suggest
      that the telomerized cells preserved the normal mechanisms of regulation of cell
      proliferation.

PMID- 12816050
TI  - [Isolation of ES-like lines of common voles of the genus Microtus from
      blastocysts and germ cells and as a result of the fusion of somatic cells with
      mouse embryonic stem cells].
AB  - Three and four independent cell lines with limited pluripotency were obtained
      from the inner cell mass cells of blastocysts and primordial germ cells of common
      voles, respectively. The results of cytogenetic analysis suggest that all these
      lines originated from the embryos of F1 Microtus rossiaemeridionalis x M. arvalis
      males and had a great number of near-triploid cells already during the early
      passages. The cells of these lines, like those of the inner cell mass, were
      characterized by the alkaline phosphatase activity. Nine independent cell lines
      were obtained as a result of hybridization of the mouse embryonic stem cells and
      vole splenocytes: eight lines and one line from hybridization with the M.
      kirgisorum and M. rossiaemeridionalis splenocytes, respectively. The cells of
      these lines expressed some properties of embryonic stem lines had a chromosome
      complement similar to the sum of two initial diploid sets of the mouse and vole.

PMID- 12816051
TI  - [Influence of regulatory genes of type 1 human immunodeficiency virus on
      proliferation and differentiation of murine embryonic stem cells].
AB  - Spontaneous formation of embryoid bodies and subsequent differentiation of some
      cells into cardiomyocytes were demonstrated on murine embryonic stem cells of R1
      line. The lines of embryonic stem cells were obtained that had been transfected
      with genetic constructs carrying expressing regulatory genes of the human
      immunodeficiency virus tat and nef and "green protein" gene (GFP). The
      transfection of embryonic stem cells with the gene tat stimulated their
      proliferative activity, while this activity decreased in the cells transfected
      with the gene nef. The time necessary for the formation of embryoid bodies by all
      lines of transfected cells was similar to that in the control cells. In the
      cultures of cells transfected with nef and tat, the number of embryoid bodies and
      the percentage of embryoid bodies with contracting cardiomyocytes were higher and
      lower than in the control, respectively. Thus, an inverse correlation was
      observed between the effects of regulatory genes of the human immunodeficiency
      virus on proliferation and differentiation embryonic stem cells.

PMID- 12816052
TI  - [Neural stem and progenitor cells of human embryos and fetuses as a basis of
      biomedical new technologies].
AB  - Isolation and cultivation of stem and progenitor cells of human embryos and
      fetuses at the age of 7-12 weeks of gestation have been described. The embryonic
      cells of human brain formed neurospheres with heterogenous composition. Cell
      differentiation took place not only in the presence of serum or as a result of
      attachment of neurosphere to a sublayer, but also in floating neurospheres in the
      presence of mitogens. In most neurospheres, the nestin-immunopositive cells were
      located near the surface while the cells stained for beta-tubulin III and glial
      fibrillar acid protein, as compact groups inside the neurospheres.

PMID- 12816053
TI  - ["Chromosome memory" of parental genomes in embryonic hybrid cells].
AB  - In the hybrid cells obtained by fusion of embryonic stem cells with adult
      differentiated cells, homologous chromosomes are in two ontogenetic
      configurations: pluripotent and differentiated. In order to assess the role of
      cis- and trans-regulation in the maintenance of these states, we studied a set of
      clones of hybrid cells of the type embryonic stem cells-splenocytes and used two
      approaches: segregation of parental chromosomes and comparison of pluripotency of
      the past hybrid cells and embryonic stem cells. The segregation test showed that
      the hybrid cells lost only the homologs of the somatic partner and this process
      was sharply accelerated when the cells were cultivated in nonselective
      conditions, thus suggesting the full or partial preservation of the initial
      differences in the organization of parental homologs. The descendants of the
      former hybrid cells, which had the karyotype similar to that of embryonic stem
      cells, demonstrated the level of pluripotency, comparable with that of embryonic
      stem cells despite the long-term effect of trans-acting factors from the somatic
      partner in the genome of hybrid cells. The data obtained are interpreted in the
      framework of the concept of "chromosome memory", in the maintenance of which the
      key role is played by cis-regulatory factors.

PMID- 12816054
TI  - [Pluripotency of bone marrow stromal cells and perspectives of their use in cell
      therapy].
AB  - The possibility of differentiation of insulin-producing cells and neural and
      glial elements was demonstrated in the culture of bone marrow stromal cells. The
      perspectives of use of the bone marrow stromal cells in clinical medicine are
      considered.

PMID- 12816055
TI  - [All-Russian conference "Cell and tissue engineering of plants and animals"].

PMID- 12816056
TI  - [Myeloperoxidase from neutrophil peroxisomes].
AB  - Peroxisomal myeloperoxidase plays a key role in synthesis of oxidants by
      neutrophilic leukocytes. This heme protein consists of two subunits connected by
      a disulfide bond. The enzyme uses H2O2 and Cl- for synthesis of HOCl--the major
      oxidant produced by neutrophils. Besides the chlorination reaction,
      myeloperoxidase exhibits some other properties depending on its oxidation state.
      The enzyme significantly affects synthesis of oxidants in the cells depending on
      the competing substrate concentrations and other factors. O2.- is also a
      physiological substrate of myeloperoxidase. Its reaction with the enzyme
      determines how the cells utilize O2.- for pathogen elimination. O2.- affects the
      chlorinating and peroxidase activities of myeloperoxidase. In addition, O2.-
      reacts with the enzyme yielding the catalytically active compound III that
      hydroxylates phenols.

PMID- 12816057
TI  - [Inhibitors of protein biosynthesis can stimulate proliferation of mouse
      hepatocytes in vitro].
AB  - Hepatocyte proliferation in the liver regenerating after partial hepatectomy
      ceases when the organ is restored, and the mechanism of this phenomenon is still
      unclear. In the experiments on fusing hepatocytes from the regenerated mouse
      liver (15 days after partial hepatectomy) with NIH 3T3 mouse fibroblasts, we
      revealed no DNA synthesis in the nuclei of stimulated fibroblasts in
      heterokaryons (in the presence of hepatocyte nuclei), whereas DNA synthesis in
      nonfused cells was undisturbed. In this work, our purpose was to find out whether
      the suppression of DNA synthesis in heterokaryons could be due to the appearance
      in hepatocytes of some endogenous factors having an inhibitory effect on
      proliferation. To this end, hepatocytes from the mouse liver regenerated after
      partial hepatectomy were treated with cycloheximide for 1-4 h and were then fused
      with stimulated fibroblasts. Such a short-term treatment of hepatocytes with
      cycloheximide proved to result in the loss of their ability to inhibit DNA
      synthesis in the nuclei of stimulated or quiescent fibroblasts in heterokaryons,
      but hepatocytes proper actively proliferated in the medium with a low serum
      content (0.2%). When the mice with the liver regenerated after partial
      hepatectomy were treated with a single sublethal dose of cycloheximide (3 mg/kg),
      their hepatocytes taken two days after this treatment had no inhibitory effect.
      Puromycin, another inhibitor o protein synthesis, had the same effect on
      hepatocytes. These results may be interpreted as evidence that the final stage of
      liver regeneration after damage is controlled by the factors having a negative
      effect on cell proliferation.

PMID- 12816058
TI  - [Erythroid differentiation of K562 cells resistant to 2-(4'
      dimethylaminostyryl)quinoline 1-oxide or 4-nitroquinoline 1-oxide is
      significantly increased after thymidine treatment].
AB  - We studied the effect of certain differentiation inducers-thymidine, sodium
      butyrate, and dimethyl sulfoxide--on the cells of parental line K562 and the
      derived sublines resistant to quinoline xenobiotics 2-(4
      dimethylaminostyryl)quinoline 1-oxide or 4-nitroquinoline 1-oxide. The cells of
      the both derived sublines demonstrate cross-resistance to these xenobiotics,
      while the subline resistant to 2-(4-dimethylaminostyryl)quinoline 1-oxide is also
      resistant to ethidium bromide and colchicine. Treatment of cells of the sublines
      with thymidine but neither sodium butyrate nor dimethyl sulfoxide for 2 or 4 days
      considerably increases intracellular content of hemoglobin as compared to the
      parental cells K562. The revealed effect is due to increased hemoglobin content
      in the cells rather than to the increased proportion of hemoglobin-containing
      cells, which results from decreased proliferation rate observed in all cases.

PMID- 12816059
TI  - [Age factor in eye regeneration of the gastropod mollusk Achatina fulica].
AB  - The dependence of the ability to regenerate the eye on the age of experimental
      animals was studied in the snail Achatina fulica. The degree of regeneration was
      estimated by light-microscopic and electrophysiological methods and by analyzing
      the motor response to visual stimuli. In older age groups, the number of
      regenerated eye-bearing tentacles decreased, whereas the period of regeneration
      increased. The regenerated eyes of the snails operated at the age of more than
      two months remained smaller than normal eyes even after six months. Regeneration
      of the distal part of the optic nerve was observed, and the regenerated eyes
      recovered the ability to respond to stimulation by light. In the
      electroretinogram, the responses of the regenerated eye, compared to the control,
      were characterised by a lower amplitude and longer repolarization and refractory
      periods. Manifestations of the motor response to visual stimuli in the young
      snails with regenerating eyes could be regarded as evidence for the recovery of
      connection between the organ of sight and the central ganglia.

PMID- 12816060
TI  - [Effect of gamma-aminobutyric shunt metabolites on NAD-, NADP-isocitrate
      dehydrogenases, and aconitate hydratase activities in higher plants].
AB  - We studied the influence of metabolites of gamma-aminobutyric shunt of the
      tricarboxylic acid cycle on the activities of aconitate hydratase (EC.4.2.1.3) as
      well as NAD- and NADP-specific isocitrate dehydrogenases (EC.1.1.1.41 and
      EC.1.1.1.42, respectively) using purified enzyme preparations from pea leaves
      (Pisum sativum L.) and maize scutellum (Zea mays L.). gamma-Aminobutyric acid and
      succinate proved to have no significant effect on these enzymes, while 0.1-0.2 mM
      glutamate considerably activated NADP isocitrate dehydrogenase from the both
      sources, particularly, at unsaturating concentration of the substrate. Succinic
      semialdehyde stimulated the activities of aconitate hydratase and NADP isocitrate
      dehydrogenase. The obtained data points to a similar pattern of the effect of
      intermediates of gamma-aminobutyric shunt on the studied enzymatic activities for
      both photosynthetic tissues (pea leaves) and those with acidifying, transport,
      and digestive functions (maize scutellum). However, the absence of pronounced
      control effects of most metabolites on the studied enzymes allows us to assign
      them to a relatively inert pool of metabolites.